PMID- 30273167
TI  - Event-Based Multiagent Consensus Control: Zeno-Free Triggering via Lp Signals.
AB  - In this paper, we develop some new event-triggered algorithms for achieving
      distributed consensus for a multiagent system that guarantees fully Zeno-free
      triggerings for all the agents. In the proposed framework, each agent updates its
      control input only at its own triggering instants by using local measurements
      (i.e., relative states) with respect to neighboring agents, and such local
      measurements can be done in a local coordinate frame. For all agents, a positive
      Lp signal function is embedded in the event detector functions, which aims to
      avoid the possible comparison of an event error term to a zero threshold that may
      happen in a zero-crossing scenario. We further propose a Zeno-free self-triggered
      algorithm to achieve multiagent consensus, which enables discrete-time
      measurements and thus avoids continuous measurements between the neighboring
      agents. We also show that the proposed event-based consensus algorithms guarantee
      less frequent triggered events in a bounded time interval compared to the
      conventional algorithm without Lp signals. Simulations and comparisons are
      provided to validate the performance and effectiveness of the proposed event
      based consensus schemes.

PMID- 30273168
TI  - Ensemble Decision for Spam Detection Using Term Space Partition Approach.
AB  - This paper proposes an ensemble decision approach which combines global and local
      features of e-mails together to detect spam effectively. In the proposed method,
      a special feature construction method named term space partition (TSP) is
      utilized to divide the whole term space into several subspaces and adopt
      different feature construction strategies on each of them, respectively. This
      method can make each term play a distinct and important role when conducting
      detection. This method is utilized and extended by introducing the sliding window
      technique to extract local features from e-mails. The global classifier and local
      classifiers are constructed on a global feature vector set and local feature
      vector sets, respectively, and together make the ensemble decision by adopting
      the voting technique. The principles of the TSP-based approach and mechanism of
      the ensemble decision method are presented in detail. Five different and standard
      benchmark corpora are applied to experiments for performance evaluation of this
      proposed method. Comprehensive experimental results show that the proposed method
      brings significant performance improvement and better robustness on the basis of
      the TSP-based approach. In addition, the proposed method outperforms the current
      prevalent and state-of-the-art approaches, especially when a comprehensive
      consideration of performance, efficiency, and robustness is taken. This endows it
      with flexible capability and adaptivity in the real-world applications.

PMID- 30273169
TI  - SCH-GAN: Semi-Supervised Cross-Modal Hashing by Generative Adversarial Network.
AB  - Cross-modal hashing maps heterogeneous multimedia data into a common Hamming
      space to realize fast and flexible cross-modal retrieval. Supervised cross-modal
      hashing methods have achieved considerable progress by incorporating semantic
      side information. However, they heavily rely on large-scale labeled cross-modal
      training data which are hard to obtain, since multiple modalities are involved.
      They also ignore the rich information contained in the large amount of unlabeled
      data across different modalities, which can help to model the correlations
      between different modalities. To address these problems, in this paper, we
      propose a novel semi-supervised cross-modal hashing approach by generative
      adversarial network (SCH-GAN). The main contributions can be summarized as
      follows: 1) we propose a novel generative adversarial network for cross-modal
      hashing, in which the generative model tries to select margin examples of one
      modality from unlabeled data when given a query of another modality (e.g., giving
      a text query to retrieve images and vice versa). The discriminative model tries
      to distinguish the selected examples and true positive examples of the query.
      These two models play a minimax game so that the generative model can promote the
      hashing performance of the discriminative model and 2) we propose a reinforcement
      learning-based algorithm to drive the training of proposed SCH-GAN. The
      generative model takes the correlation score predicted by discriminative model as
      a reward, and tries to select the examples close to the margin to promote a
      discriminative model. Extensive experiments verify the effectiveness of our
      proposed approach, compared with nine state-of-the-art methods on three widely
      used datasets.

PMID- 30273170
TI  - Multipoint Rendezvous in Multirobot Systems.
AB  - Multirobot rendezvous control and coordination strategies have garnered
      significant interest in recent years because of their potential applications in
      decentralized tasks. In this paper, we introduce a coordinate-free rendezvous
      control strategy to enable multiple robots to gather at different locations
      (dynamic leader robots) by tracking their hierarchy in a connected interaction
      graph. A key novelty in this strategy is the gathering of robots in different
      groups rather than at a single consensus point, motivated by autonomous
      multipoint recharging and flocking control problems. We show that the proposed
      rendezvous strategy guarantees convergence and maintains connectivity while
      accounting for practical considerations such as robots with limited speeds and an
      obstacle-rich environment. The algorithm is distributed and handles minor faults
      such as a broken immobile robot and a sudden link failure. In addition, we
      propose an approach that determines the locations of rendezvous points based on
      the connected interaction topology and indirectly optimizes the total energy
      consumption for rendezvous in all robots. Through extensive experiments with the
      Robotarium multirobot testbed, we verified and demonstrated the effectiveness of
      our approach and its properties.

PMID- 30273171
TI  - Alignment-Supervised Bidimensional Attention-Based Recursive Autoencoders for
      Bilingual Phrase Representation.
AB  - Exploiting semantic interactions between the source and target linguistic items
      at different levels of granularity is crucial for generating compact vector
      representations for bilingual phrases. To achieve this, we propose alignment
      supervised bidimensional attention-based recursive autoencoders (ABattRAE) in
      this paper. ABattRAE first individually employs two recursive autoencoders to
      recover hierarchical tree structures of bilingual phrase, and treats the
      subphrase covered by each node on the tree as a linguistic item. Unlike previous
      methods, ABattRAE introduces a bidimensional attention network to measure the
      semantic matching degree between linguistic items of different languages, which
      enables our model to integrate information from all nodes by dynamically
      assigning varying weights to their corresponding embeddings. To ensure the
      accuracy of the generated attention weights in the attention network, ABattRAE
      incorporates word alignments as supervision signals to guide the learning
      procedure. Using the general stochastic gradient descent algorithm, we train our
      model in an end-to-end fashion, where the semantic similarity of translation
      equivalents is maximized while the semantic similarity of nontranslation pairs is
      minimized. Finally, we incorporate a semantic feature based on the learned
      bilingual phrase representations into a machine translation system for better
      translation selection. Experimental results on NIST Chinese-English and WMT
      English-German test sets show that our model achieves substantial improvements of
      up to 2.86 and 1.09 BLEU points over the baseline, respectively. Extensive in
      depth analyses demonstrate the superiority of our model in learning bilingual
      phrase embeddings.

PMID- 30273172
TI  - Products of Generalized Stochastic Matrices With Applications to Consensus
      Analysis in Networks of Multiagents With Delays.
AB  - Product theory of stochastic matrices provides a powerful tool in the consensus
      analysis of discrete-time multiagent systems. However, the classic theory cannot
      deal with networks with general coupling coefficients involving negative ones,
      which have been discussed only in very few papers due to the technicalities
      involved. Motivated by these works, here we developed some new results for the
      products of matrices which generalize that of the classical stochastic matrices
      by admitting negative entries. Particularly, we obtained a generalized version of
      the classic Hajnal inequality on this generalized matrix class. Based on these
      results, we proved some convergence results for a class of discrete-time
      consensus algorithms with time-varying delays and general coupling coefficients.
      At last, these results were applied to the analysis of a class of continuous-time
      consensus algorithms with discrete-time controller updates in the existence of
      communication/actuation delays.

PMID- 30273173
TI  - Event-Triggered Adaptive Tracking Control for Multiagent Systems With Unknown
      Disturbances.
AB  - This paper considers the event-triggered tracking control problem of nonlinear
      multiagent systems with unknown disturbances. The event-triggering mechanism is
      considered in the controller update, which decreases the amount of communication
      and reduces the frequency of the controller update in practice. By designing a
      disturbance observer, the unknown external disturbances are estimated. Moreover,
      a part of adaptive parameters are only dependent on the number of followers,
      which weakens the computational burden. It is shown that all the signals are
      bounded, and the consensus tracking errors are located in a small neighborhood of
      the origin based on the Lyapunov stability theory and backstepping approach.
      Finally, the effectiveness of the approach proposed in this paper is proved by
      simulation results.

PMID- 30273174
TI  - Consensus-Based Odor Source Localization by Multiagent Systems.
AB  - This paper presents an investigation of the task of localizing an unknown source
      of an odor by heterogeneous multiagent systems. A hierarchical cooperative
      control strategy has been proposed as a potential candidate to solve the problem.
      The agents are driven into consensus as soon as the information about the
      location of source is acquired. The controller has been designed in a
      hierarchical manner of group decision making, agent path planning, and robust
      control. In group decision making, the particle swarm optimization algorithm has
      been used along with the information of the movement of odor molecules to predict
      the odor source location. Next, a trajectory has been mapped using this predicted
      location of source, and the information is passed to the control layer. A
      variable structure control has been used in the control layer due to its inherent
      robustness and disturbance rejection capabilities. Cases of movement of agents
      toward the source under consensus and parallel formation have been discussed. The
      efficacy of the proposed scheme has been confirmed by simulations.

PMID- 30273175
TI  - Average Quasi-Consensus Algorithm for Distributed Constrained Optimization:
      Impulsive Communication Framework.
AB  - This paper presents the impulsive average quasi-consensus algorithm for
      distributed constrained convex optimization. First, the constrained optimization
      problem can be transformed into an unconstrained problem using the interior point
      method, and then a distributed algorithm is modeled by means of impulsive
      differential equation. In the framework of the continuous-time gradient method
      and algebraic graph theory, each agent can deal with one local objective function
      with local constraints. At the impulsive instants, each agent can communicate
      with its neighboring agents over the network. Under certain conditions, the
      impulsive average quasi-consensus is achieved. It is shown that the state of
      average quasi-consensus is the optimal solution of the aforementioned
      unconstrained optimization problem, and the state of each agent can also reach
      the neighborhood of the optimal solution. Finally, two numerical examples show
      the effectiveness of the proposed impulsive average quasi-consensus algorithm.
      Moreover, the feasibility of the approach is verified by an application to one
      sensor network localization problem.

PMID- 30273176
TI  - Relative Degrees and Implicit Function-Based Control of Discrete-Time
      Noncanonical Form Neural Network Systems.
AB  - This paper studies the relative degrees of discrete-time neural network systems
      in a general noncanonical form, and develops a new feedback control scheme for
      such systems, based on implicit function theory and feedback linearization. After
      time-advance operation on output of such systems, the output dynamics nonlinearly
      depends on the control input. To address this issue, we use implicit function
      theory to define the relative degrees, and to establish a normal form. Then, an
      implicit function equation solution-based control scheme and an iterative
      solution-based control scheme are proposed, which ensure not only the closed-loop
      stability but also the output tracking for the controlled plant. An adaptive
      control framework for the controlled plant with uncertainties is also presented
      to illustrate the basic design procedure. The simulation results are given to
      demonstrate the desired system performance.

PMID- 30273177
TI  - Cooperative Control of Multiple Nonlinear Benchmark Systems Perturbed by Second
      Order Moment Processes.
AB  - This paper studies the cooperative control problem of multiple nonlinear
      benchmark systems perturbed by second-order moment processes. The nonlinear
      benchmark system consists of a moving car and a rolling ball in oscillating
      surroundings. When the leader is only accessible to a small part of the followers
      in a directed graph, a new vectorial backstepping method is proposed for the
      design of distributed cooperative control laws. By using stochastic analysis
      techniques and algebra graph theory, it is shown that the cooperative control
      problem under consideration is solvable. Specifically, the errors between the
      followers' outputs and the leader's output can be made arbitrarily small while
      keeping all states of the closed-loop system bounded in probability. Finally, the
      effectiveness of the proposed control scheme is demonstrated through a simulation
      example.

PMID- 30273178
TI  - Event-Based Control for Networked T-S Fuzzy Systems via Auxiliary Random Series
      Approach.
AB  - This paper presents an auxiliary random series approach to model the effect of
      network induced problems, such as data losses and transmission delay subject to
      event-based communication scheme for nonlinear continuous time systems. T-S fuzzy
      model is employed to describe the nonlinear systems. In order to save the
      bandwidth and energy, we introduce the event-triggered mechanism to reduce the
      number of data for transmission and computation. Thus, it is necessary to
      consider the influence of data losses, data disorder, and transmission delay
      since the transmitted data packets become more important. Consequently, it is
      very complicated to analyze the performance of such networked system and one of
      the most difficult part, in the authors' opinion, is to construct the
      mathematical model of closed-loop systems. In this paper, we present an auxiliary
      random series approach to describe the data transmitted in the system, and
      therefore, the closed-loop systems can be obtained. Associated with a tailor-made
      Lyapunov-Krasovskii functional, the stability analysis is processed and a fuzzy
      controller is designed. Asynchronous membership functions are considered to
      obtain more relaxed stability conditions. To clarify the effectiveness of the
      proposed method, a cart-damper-spring system is employed for simulation.

PMID- 30273179
TI  - Enhancing Gaussian Estimation of Distribution Algorithm by Exploiting Evolution
      Direction With Archive.
AB  - As a typical model-based evolutionary algorithm, estimation of distribution
      algorithm (EDA) possesses unique characteristics and has been widely applied in
      global optimization. However, the commonly used Gaussian EDA (GEDA) usually
      suffers from premature convergence, which severely limits its search efficiency.
      This paper first systematically analyzes the reasons for the deficiency of
      traditional GEDA, then tries to enhance its performance by exploiting the
      evolution direction, and finally develops a new GEDA variant named EDA2. Instead
      of only utilizing some good solutions produced in the current generation to
      estimate the Gaussian model, EDA2 preserves a certain number of high-quality
      solutions generated in the previous generations into an archive and employs these
      historical solutions to assist estimating the covariance matrix of Gaussian
      model. By this means, the evolution direction information hidden in the archive
      is naturally integrated into the estimated model, which in turn can guide EDA2
      toward more promising solution regions. Moreover, the new estimation method
      significantly reduces the population size of EDA2 since it needs fewer
      individuals in the current population for model estimation. As a result, a fast
      convergence can be achieved. To verify the efficiency of EDA2, we tested it on a
      variety of benchmark functions and compared it with several state-of-the-art EAs.
      The experimental results demonstrate that EDA2 is efficient and competitive.

PMID- 30273180
TI  - A Random Forest-Assisted Evolutionary Algorithm for Data-Driven Constrained
      Multiobjective Combinatorial Optimization of Trauma Systems.
AB  - Many real-world optimization problems can be solved by using the data-driven
      approach only, simply because no analytic objective functions are available for
      evaluating candidate solutions. In this paper, we address a class of expensive
      data-driven constrained multiobjective combinatorial optimization problems, where
      the objectives and constraints can be calculated only on the basis of a large
      amount of data. To solve this class of problems, we propose using random forests
      (RFs) and radial basis function networks as surrogates to approximate both
      objective and constraint functions. In addition, logistic regression models are
      introduced to rectify the surrogate-assisted fitness evaluations and a stochastic
      ranking selection is adopted to further reduce the influences of the approximated
      constraint functions. Three variants of the proposed algorithm are empirically
      evaluated on multiobjective knapsack benchmark problems and two real-world trauma
      system design problems. Experimental results demonstrate that the variant using
      RF models as the surrogates is effective and efficient in solving data-driven
      constrained multiobjective combinatorial optimization problems.

PMID- 30273181
TI  - Containment Control for General Second-Order Multiagent Systems With Switched
      Dynamics.
AB  - This paper investigates the distributed containment control problem for a class
      of general second-order multiagent systems with switched dynamics, which is
      composed of a continuous-time (CT) subsystem and a discrete-time (DT) subsystem.
      For this switched multiagent system under fixed directed topology, a distributed
      containment control protocol is proposed for each follower based on the relative
      local measurements of neighboring followers and leaders. Some necessary and
      sufficient conditions are derived under the condition that the network topology
      contains a directed spanning forest, and these conditions ensure that the general
      second-order containment control problem can be solved under arbitrary CT-DT
      switching. If the general second-order system is reduced to the double integrator
      system, some simpler containment conditions are presented. Furthermore, the
      similar results are also obtained under switching directed topology. Finally,
      some simulation examples are presented to show the efficiency of the theoretical
      results.

PMID- 30273182
TI  - MicroRNA-195 reverses the resistance to temozolomide through targeting cyclin E1
      in glioma cells.
AB  - Glioma is the most common malignant tumor of the central nervous system with poor
      survival. Temozolomide (TMZ) is the first-line chemotherapy drug for initial and
      recurrent glioma treatment with a relatively good efficacy, which exerts its
      antitumor effects mainly through cell death induced by DNA double-strand breaks
      in the G1 and S phases. However, endogenous or acquired resistance to TMZ limits
      glioma patients' clinical outcome and is also an important cause of glioma
      replase. MicroRNA-195 (miR-195) plays an important role in the regulation of G1
      phase/S-phase transition, DNA damage repair, and apoptosis of tumor cells. We
      found that miR-195 expression was significantly decreased in TMZ-resistant glioma
      cells induced with TMZ and correlated to the resistance index negatively. Also,
      the exogenous expression of miR-195 reversed TMZ resistance and induced the
      apoptosis of TMZ-resistant glioblastoma cells. Further bioinformatics analysis
      showed cyclin E1 (CCNE1) was a potential target gene of miR-195. Knockdown of
      CCNE1 partially reversed the effect of decreased miR-195 on TMZ resistance. The
      data from The Cancer Genome Atlas - Cancer Genome further suggested that hsa-miR
      195 could negatively regulate the expression of CCNE1 in glioma. In conclusion,
      miR-195 reverses the resistance to TMZ by targeting CCNE1 in glioma cells and it
      could act as a potential target for treatment in glioma with TMZ resistance.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- 30273183
TI  - Long-term clinical outcomes after treatment of stent restenosis with two drug
      coated balloons.
AB  - BACKGROUND: Treatment of in-stent restenosis (ISR) is still a clinical challenge
      in interventional cardiology. Paclitaxel-coated balloons (PCBs) are an attractive
      therapeutic option for ISR. There are several different types of PCBs available
      for percutaneous coronary intervention, but to date, comparative data between
      different types of PCBs for the treatment of ISR are scarce. PATIENTS AND
      METHODS: This single centre, nonrandomized, retrospective study under real-world
      condition included 194 patients with 194 ISR treated by repeat percutaneous
      coronary intervention with PCBs. The primary end point was major adverse cardiac
      events (MACEs), defined as cardiac death, myocardial infarction and need for
      target lesion revascularization (TLR) at 1 year. Secondary end points were MACE
      and TLR at long-term follow-up. RESULTS: Baseline clinical and angiographic
      parameters were comparable between the two groups. Patients in the iopromide
      based PCB and butyryl-tri-hexyl citrate (BTHC)-PCB groups were followed up for
      32.2+/-20.5 and 24.2+/-13.3 months, respectively (P=0.001). MACEs at 1-year
      follow-up were 15.0 and 15.8% (P=0.879) for the BTHC-PCB and iopromide-based PCB
      groups, respectively. TLR, myocardial infarction and cardiac death for BTHC-PCB
      versus iopromide-based PCB at 1-year follow-up were 9.6 versus 11.8%, P=0.622;
      5.3 versus 3.9%, P=0.640; and 5.3 versus 3.9%, P=0.640, respectively. If complete
      follow-up periods were included in the analysis, BTHC-PCB and iopromide-based PCB
      had comparable rates of MACE (P=0.835) and TLR (P=0.792). CONCLUSION: BTHC-PCB
      and iopromide-based PCB had comparable rates of MACE and TLR for the treatment of
      ISR at 1-year and long-term follow-up.

PMID- 30273184
TI  - The Partnership for Accelerating Cancer Therapies.
AB  - As a part of the Cancer Moonshot, the National Cancer Institute, part of the
      National Institutes of Health, the Foundation for National Institutes of Health,
      the US Food and Drug Administration, and 12 pharmaceutical companies have formed
      a 5-year, $220 million precompetitive public-private research collaboration
      called the Partnership for Accelerating Cancer Therapies. A systematic cross
      sector effort to identify and develop robust, standardized biomarkers and related
      clinical data, Partnership for Accelerating Cancer Therapies will support the
      selection and testing of promising immunotherapies for the treatment of cancer,
      with the goal of bringing effective therapy to more patients.

PMID- 30273185
TI  - Comparison of Pain-reducing Effect After Selective Nerve Root Block According to
      the Type of Lumbar Foraminal Stenosis.
AB  - STUDY DESIGN: This was a nonrandomized controlled cohort study (level 3).
      OBJECTIVE: This study was designed to compare the differences in clinical
      features among patients with various degrees of lumbar foraminal stenosis (LFS),
      and the therapeutic effect of selective nerve root block (SNRB). SUMMARY OF
      BACKGROUND DATA: Symptomatic improvement rate was lower in grade IV (0.377) than
      in other grades (1T: 0.612, 2:0.527, 3:0.551), with statistical significance
      (P=0.03). PATIENTS AND METHODS: A total of 233 patients with radiating pain,
      concurrent with neurological and radiologic findings, were assigned to receive
      SNRB for at least 1 level, and screened for >=6 months. The degree of foraminal
      stenosis was classified by perineural fat obliteration, and the degree of
      radiating pain was assessed by visual analog scale. After SNRBs were performed,
      symptomatic improvement was assessed after 2, 12, and 24 weeks after injection.
      RESULTS: There were no significant differences in visual analog scale with regard
      to the degree of stenosis. Improvements were significantly higher after 2 weeks
      (P=0.030), and there were no significant differences in symptomatic improvement
      rates over time except LFS grade 1V. At 2 weeks after injection, there was no
      significant difference in the extent of symptomatic improvement between the
      grades. At 12 and 24 weeks after injection, patients with LFS grade 1T, 2, 3
      showed significantly higher symptomatic improvement rates than patients with LFS
      grade 1V. CONCLUSIONS: Among the patients with LFS, SNRB reduced pain by 51%
      after 2 weeks. At after 12 weeks, SNRBs were more effective in patients with LFS
      grade 1T, 2, 3, compared with patients with grade 1V. All patients showed
      persistent symptomatic relief, whereas those with grade 1T showed a reduced
      degree of symptomatic relief after 2 weeks.

PMID- 30273186
TI  - Surgical Treatment of Dystrophic Scoliosis in Neurofibromatosis Type 1: Outcomes
      and Complications.
AB  - STUDY DESIGN: This is a retrospective cohort study. OBJECTIVE: To investigate
      surgical outcomes and instrumentation-related complications (IRCs) of dystrophic
      scoliosis associated with neurofibromatosis type 1 (NF-1). SUMMARY OF BACKGROUND
      DATA: Surgical management, including the growing rod technique and early
      definitive fusion, has been recommended to avoid progression of NF-1 scoliosis.
      However, no study has investigated the outcomes and complications of different
      surgical interventions. MATERIALS AND METHODS: We performed a retrospective
      review of a cohort of 59 patients diagnosed with NF-1 dystrophic scoliosis and
      treated surgically. All clinical and radiographic data within a 3-year follow-up
      period were collected. The patients were divided into 2 groups according to the
      surgical procedure used: those who underwent initial fusion surgery were assigned
      to group A (n=32) and those who underwent growing rod surgery to group B (n=27).
      RESULTS: Patients in group A were older than those in group B at the initial
      surgery (10.4 vs. 5.8 y; P<0.001). There was no difference in the sex ratio,
      preoperative Cobb angle, or preoperative kyphosis angle between the 2 groups
      (P>0.05). The correction rate of the main curve Cobb angle was higher in group A
      than B (55.1% vs. 42.4%; P<0.05). The incidence of IRC was higher in group B than
      A (48.1% vs. 12.5%; P<0.05). Complications in group A comprised 1 case of screw
      pullout, 1 case of rod breakage, 1 case of adding-on phenomenon, and 1 case of
      proximal junctional kyphosis. Complications in group B comprised 5 cases of
      adding-on phenomenon, 4 cases of trunk shift, 3 cases of curve progression, 1
      case of rod breakage, and 1 case of cap loosening. CONCLUSIONS: The use of
      growing rod effectively controls the spinal deformity and facilitates growth of
      the spine. Compared with fusion surgery, however, growing rod surgery yields a
      higher incidence of IRCs and lower corrective rate for scoliosis associated with
      NF-1.

PMID- 30273187
TI  - Relation Between Infant Microbiota and Autism?: Results from a National Cohort
      Sibling Design Study.
AB  - BACKGROUND: Hypotheses concerning adverse effects of changes in microbiota have
      received much recent attention, but unobserved confounding makes them difficult
      to test. We investigated whether surrogate markers for potential adverse
      microbiota change in infancy affected autism risk, addressing unobserved
      confounding using a sibling study design. METHODS: This is a population-based,
      prospective cohort study including all singleton live births in Denmark from 1997
      to 2010. The exposure variables were cesarean delivery and antibiotic use in the
      first 2 years of life. The outcome was a subsequent autism diagnosis. We used the
      between- and within-sibling model and compared it with sibling-stratified Cox
      models and simpler standard Cox models that ignored sibship. RESULTS: Of our
      study population including 671,606 children, who were followed for up to 15 years
      (7,341,133 person-years), 72% received antibiotics, 17.5% were delivered by
      cesarean, and 1.2% (8,267) developed autism. The standard Cox models predicted
      that both cesarean (compared with vaginal) delivery and antibiotics increased the
      risk of autism. In the sibling-stratified Cox model, only broader spectrum
      antibiotics were associated with increased risk of autism: hazard ratio (HR) =
      1.16 (95% confidence interval = 1.01, 1.36). The between-within model estimated
      no exposure effects: intrapartum cesarean HR = 1.06 (0.89, 1.26); prelabor
      cesarean HR = 0.97 (0.83, 1.15); exclusively penicillin HR = 1.05 (0.93, 1.18);
      and broader spectrum antibiotics HR = 1.05 (0.95, 1.16). CONCLUSIONS: The between
      within model rendered more precise estimates than sibling-stratified Cox models,
      and we believe that it also provided more valid estimates. Results from these
      preferred models do not support a causal relation between antibiotic treatment
      during infancy, cesarean delivery, and autism. See video abstract at,
      http://links.lww.com/EDE/B432.

PMID- 30273189
TI  - Urinary Retention Associated With Cariprazine: A Case Report.
AB  - Urinary retention is a well-documented adverse effect of antipsychotic
      medications and is thought to be mediated by anticholinergic, adrenergic, and
      other neurotransmitter effects. Whereas urinary retention has been reported with
      typical and some atypical antipsychotics, there have been no reports of urinary
      retention with the novel antipsychotic cariprazine. We report on a case of
      urinary retention associated with cariprazine. Possible mechanisms for this
      adverse effect are discussed.

PMID- 30273190
TI  - Adjunctive Donepezil for Anxiety Symptoms With Poor Response to Paroxetine in a
      Patient With Probable Mild Cognitive Impairment.

PMID- 30273188
TI  - Cumulative Human Immunodeficiency Viremia, Antiretroviral Therapy, and Incident
      Myocardial Infarction.
AB  - BACKGROUND: People living with HIV are at risk of increased myocardial infarction
      (MI). Cumulative HIV viral load (VL) has been proposed as a better measure of HIV
      inflammation than other measures of VL, like baseline VL, but its associations
      with MI are not known. METHODS: The multisite Centers for AIDS Research Network
      of Integrated Clinical Systems (CNICS) cohort includes clinical data and
      centrally adjudicated MI with distinction between atheroembolic MI (type 1) and
      MI related to supply-demand mismatch (type 2). We examined CNICS participants who
      were not on antiretroviral therapy (ART) at enrollment. Cumulative VL (copy-days
      of virus) from 6 months after enrollment was estimated with a time-weighted sum
      using the trapezoidal rule. We modeled associations of cumulative and baseline VL
      with MI by type using marginal structural Cox models. We contrasted the 75%
      percentile of the VL distribution with the 25% percentile. RESULTS: Among 11,324
      participants, 218 MIs occurred between 1996 and 2016. Higher cumulative VL was
      associated with risk of all MI (hazard ratio [HR] = 1.72; 95% confidence interval
      [CI] = 1.26, 2.36), type 1 MI (HR = 1.23; 95% CI = 0.78, 1.96), and type 2 MI (HR
      = 2.52; 95% CI = 1.74, 3.66). While off ART, cumulative VL had a stronger
      association with type 1 MI (HR = 2.13; 95% CI = 1.15, 3.94) than type 2 MI (HR =
      1.25; 95% CI = 0.70, 2.25). Baseline VL was associated with all MI (HR = 1.60;
      95% CI = 1.28, 2.01), type 1 MI (HR = 1.73; 95% CI = 1.26, 2.38), and type 2 MI
      (HR = 1.51; 95% CI = 1.10, 2.08). CONCLUSIONS: Higher cumulative and baseline VL
      is associated with all MI, with a particularly strong association between
      cumulative VL and type 2 MI.

PMID- 30273191
TI  - Fludarabine-Induced Posterior Reversible Encephalopathy Syndrome in a Pediatric
      Patient With beta-Thalassemia: Case Report and Literature Review.
AB  - Posterior reversible encephalopathy syndrome is a disorder of reversible
      subcortical vasogenic brain edema in the context of different diseases or
      exposure to cytotoxic drugs such as fludarabine. We present the case of a
      pediatric patient with beta-thalassemia who develops a fludarabine-induced
      posterior reversible encephalopathy while he received an induction regimen to
      achieve an allogenic hematopoietic cell transplantation. The clinical
      presentation consists in altered mental state, headache, status epilepticus,
      visual disturbance, and hypertension. His treatment was carried out with the
      suspension of the medication and the control of hypertension and status
      epilepticus; the final outcome was positive without additional complications.
      There are published reports about fludarabine toxicity in the central nervous
      system with different doses of the drug in different clinical context. We also
      made a review of the literature available and conclude that fludarabine is not an
      extraordinary cause of posterior reversible encephalopathy syndrome.

PMID- 30273192
TI  - Increased Risk of Ischemic Stroke in Multiple Myeloma Associated With
      Lenalidomide Treatment: A Case Report and Review of the Literature.
AB  - OBJECTIVE: The aim of the study was to illustrate the increased risk of ischemic
      stroke in the context of multiple myeloma (MM) under treatment with lenalidomide
      combined with dexamethasone. METHODS: This is a case report and literature
      review. RESULTS: A 62-year-old woman diagnosed with relapsed MM under treatment
      with lenalidomide and dexamethasone presented with acute onset disorientation,
      disturbed behavior, and aphasia. Cranial computed tomography scan revealed an
      acute cerebral infarction in the left middle cerebral artery territory, and brain
      magnetic resonance imaging showed additional silent ischemic lesions in other
      arterial territories. Common stroke etiologies were excluded after an extensive
      study, leading to a final diagnosis of cerebral infarction of uncommon cause
      probably related to MM and treatment with lenalidomide plus dexamethasone. A
      literature review provided 84 reports from the license holder, 2 more cases of
      stroke in patients with MM receiving lenalidomide and a recurrent stroke in a
      patient experiencing polyneuropathy, organomegaly, endocrinopathy, monoclonal
      gammopathy, and skin changes (POEMS syndrome) treated with lenalidomide.
      CONCLUSIONS: Our case exemplifies the need to raise awareness about the risk of
      ischemic stroke associated with MM that might be increased by treatment with
      lenalidomide and to establish consistent recommendations regarding
      thromboprophylaxis to reduce comorbidities and mortality in these patients.

PMID- 30273193
TI  - Geometric Properties of Donor Corneas After Mechanical Trephination in Deep
      Anterior Lamellar Keratoplasty.
AB  - PURPOSE: To evaluate the geometry of donor corneal buttons after mechanical
      trephination and to determine whether there were any possible variables that
      could influence the accuracy of cutting corneal buttons in deep anterior lamellar
      keratoplasty. METHODS: This cross-sectional study included 85 sclerocorneal
      buttons that were transplanted during deep anterior lamellar keratoplasty. Donor
      corneas were punched from the posterior surface. Photographs that most clearly
      represented the entire edges of the donor corneas were taken from the punched
      corneas and systematically analyzed using ImageJ software. The univariate
      analyses were used to investigate the influence of potential variables on the
      precision and roundness of the donor cut. RESULTS: The epithelial side of the
      grafts was significantly larger than the posterior side in diameter, perimeter,
      and area. The perimeter and area of the donor posterior surface and the trephine
      used for punching the grafts were the same, whereas the epithelial side had a
      significantly larger perimeter and area than those of the trephine. Graft
      roundness varied from 0.78 to 1.0 at the epithelial side and from 0.77 to 1.0 at
      the posterior side. The roundness of the scleral spur, which represented the
      shape of the donor cornea, was identified as the main predictor of the roundness
      of the donor cut (P < 0.001). CONCLUSIONS: The donor buttons after mechanical
      trephination from the posterior surface may not be circular and of the intended
      diameter; the epithelial surface dimensions were significantly larger than the
      posterior surface and trephine dimensions. The roundness of the punched graft was
      primarily affected by the roundness of the cornea before trephination.

PMID- 30273194
TI  - Age and CD20 Expression Are Significant Prognostic Factors in Human Herpes Virus
      8-negative Effusion-based Lymphoma.
AB  - Human herpes virus-8 (HHV-8)-negative effusion-based lymphoma (HHV-8-negative
      EBL) can be distinguished from primary effusion lymphoma based on clinical and
      pathologic findings. Although the morphology between the 2 is similar and they
      both originate from body cavities with serous effusions and are characterized by
      lack of tumor masses, HHV-8-negative EBL generally occurs in older patients, and
      has favorable response to therapy and better prognosis than primary effusion
      lymphoma. However, no systematic studies have investigated prognostic factors in
      patients with HHV-8-negative EBL. In this report, clinical and pathologic
      characteristics of 67 cases of HHV-8-negative EBL, including 2 of our own cases,
      were analyzed. Univariate analyses revealed older age (70 y and above), Japanese
      ethnicity, pericardial effusion, CD20 expression, and chemotherapy with rituximab
      were significantly favorable prognostic factors. Peritoneal effusion was
      identified as an unfavorable prognostic factor. In the multivariate analysis, age
      and CD20 expression were independent prognostic factors (P=0.013 and 0.003,
      respectively). A past history of induced fluid overload, hepatitis C viral
      infection, and peritoneal effusion were significantly correlated with patients
      aged below 70 years, while pericardial and pleural effusions were significantly
      correlated with patients aged 70 years and above. A comparison of cases with and
      without CD20 expression revealed that Japanese ethnicity and pericardial effusion
      were significantly correlated with CD20 expression, whereas a past history of
      induced fluid overload and peritoneal effusion were significantly correlated with
      the absence of CD20. We concluded that older age and CD20 expression are
      significant and favorable independent prognostic factors of HHV-8-negative EBL.

PMID- 30273195
TI  - Uterine Tumor Resembling Ovarian Sex Cord Tumor: A Distinct Entity Characterized
      by Recurrent NCOA2/3 Gene Fusions.
AB  - Uterine tumor resembling ovarian sex-cord tumor (UTROSCT) is a rare and
      distinctive neoplasm of unclear histogenesis, and uncertain malignant potential.
      These neoplasms morphologically resemble sex-cord stromal tumors of the ovary,
      and possess a polyphenotypic immunophenotype. Their molecular pathogenesis has
      yet to be elucidated; notably, however, tumors lack alterations found in other
      uterine tumors bearing sex-cord-like differentiation, such as endometrial stromal
      sarcoma. Following identification of an index patient with an ESR1-NCOA3 fusion
      gene by RNA-sequencing, we undertook a retrospective review for additional cases
      of UTROSCT. We identified a total of 4 patients, with an average age of 53 years
      (range, 38 to 68 y). RNA-sequencing was performed in all cases, revealing an ESR1
      NCOA3 fusion in 2 cases and one case each with related ESR1-NCOA2 and GREB1-NCOA2
      fusions. Each of the tumors showed histologic and an immunophenotype features
      within the previously reported spectrum of UTROSCT; interestingly, one case
      contained prominent spindle cell fascicles and another was largely comprised of
      sheets of small round cells. Our results demonstrate UTROSCT are defined by
      recurrent fusions involving NCOA2 or NCOA3, a finding that is directly amenable
      to diagnostic evaluation. This study confirms UTROSCT is molecularly distinct
      from endometrial stromal sarcoma, and raises intriguing new questions into the
      pathogenesis of these neoplasms and possible relationship with other NCOA fusion
      positive uterine tumors.

PMID- 30273196
TI  - Heterogeneity of Fibrosis in Liver Biopsies of Patients With Heart Failure
      Undergoing Heart Transplant Evaluation.
AB  - Liver biopsies are commonly performed in heart transplant candidates to confirm
      congestive hepatopathy (CH) and to assess the degree of fibrosis. Heterogeneity
      of fibrosis is frequent in CH, making it difficult to stage fibrosis. In this
      study, we evaluated the prevalence of heterogeneity of fibrosis and nodular
      regenerative hyperplasia (NRH) in liver biopsies with CH secondary to heart
      failure. Fifty liver biopsies with CH secondary to heart failure were reviewed.
      The fibrosis was scored on trichrome stain as follows: stage 0 for no fibrosis,
      stage 1 for zone 3 fibrosis, stage 2 for zone 3 and portal fibrosis, stage 3 for
      bridging fibrosis, and stage 4 for cirrhosis. Both stage 3 and stage 4 fibrosis
      were classified as advanced fibrosis. A predominant pattern of fibrosis and a
      secondary pattern of fibrosis, defined as a different stage of fibrosis seen in
      at least 10% of the biopsy material, if present, were recorded. A biopsy was
      considered to show heterogenous fibrosis if there was at least a 2 stage
      difference between the predominant and secondary patterns. Thirteen biopsies
      (26%) showed heterogenous fibrosis. Sixteen biopsies (32%) showed some evidence
      of advanced fibrosis: 5 had uniform advanced fibrosis, 4 had predominant pattern
      of advanced fibrosis, and advanced fibrosis was focal in 7 biopsies from 6
      patients. NRH-type changes were seen in 9 of 50 biopsies (18%). In conclusion,
      our study showed heterogenous fibrosis in the liver biopsy of a quarter of
      patients with CH due to heart failure, highlighting the limitations of fibrosis
      assessment in the biopsies, and suggests that correlation with the complete
      clinical information is essential for management decisions.

PMID- 30273197
TI  - SF3B1, NRAS, KIT, and BRAF Mutation; CD117 and cMYC Expression; and Tumoral
      Pigmentation in Sinonasal Melanomas: An Analysis With Newly Found Molecular
      Alterations and Some Population-based Molecular Differences.
AB  - Sinonasal melanomas encompass melanoma arising in the nasal cavity and paranasal
      sinuses. Despite recent advances in tumor genomics, correlation between
      mutational status and protein expression with prognosis and tumor pigmentation
      has not been carried out in sinonasal melanomas. Ninety-five sinonasal melanomas
      from 95 patients were included. As per univariate analyses, age was the only
      variable that significantly correlated with progression-free survival. SF3B1,
      NRAS, KIT, and BRAF mutations were documented in 7% (5/72), 22% (16/72), 22%
      (16/72), and 8% (6/72) of cases, respectively. Comutation was detected in 6
      cases: NRAS and KIT in 2 cases; NRAS and BRAF in 2 cases; SF3B1, KIT, and BRAF in
      one case; and SF3B1, NRAS, and KIT in one case. Correlations approaching
      statistical significance were observed between BRAF mutation status and poorer
      overall survival and progression-free survival (log-rank P-values=0.054 and
      0.061). Increased CD117 expression (33%, 29/88) and decreased nuclear cMYC
      expression (40%, 39/84) significantly correlated with cytoplasmic pigmentation.
      Several SF3B1, NRAS, and KIT mutations not previously documented in sinonasal
      melanomas were detected in our series, suggesting a potential role for targeted
      therapies. A similar frequency of SF3B1, NRAS, and KIT mutations was noted in
      Asian cases, whereas NRAS, KIT, and BRAF mutations were predominant in the United
      States and European cases; however, the number of included cases was small. The
      significant association between CD117 and cMYC expression with increased
      cytoplasmic pigmentation in our series suggests that the pigmented morphologic
      appearance of sinonasal melanomas could be attributed to the underlying oncogenic
      mutations and metabolic interaction.

PMID- 30273198
TI  - The Hexavalent CD40 Agonist HERA-CD40L Induces T-Cell-mediated Antitumor Immune
      Response Through Activation of Antigen-presenting Cells.
AB  - CD40 ligand (TNFSF5/CD154/CD40L), a member of the tumor necrosis factor (TNF)
      superfamily is a key regulator of the immune system. The cognate receptor CD40
      (TNFRSF5) is expressed broadly on antigen-presenting cells and many tumor types,
      and has emerged as an attractive target for immunologic cancer treatment. Most of
      the CD40 targeting drugs in clinical development are antibodies which display
      some disadvantages: their activity typically depends on Fcgamma receptor-mediated
      crosslinking, and depletion of CD40-expressing immune cells by antibody-dependent
      cellular cytotoxicity compromises an efficient antitumor response. To overcome
      the inadequacies of antibodies, we have developed the hexavalent receptor agonist
      (HERA) Technology. HERA compounds are fusion proteins composed of 3 receptor
      binding domains in a single chain arrangement, linked to an Fc-silenced human
      IgG1 thereby generating a hexavalent molecule. HERA-CD40L provides efficient
      receptor agonism on CD40-expressing cells and, importantly, does not require
      FcgammaR-mediated crosslinking. Strong activation of NFkappaB signaling was
      observed upon treatment of B cells with HERA-CD40L. Monocyte treatment with HERA
      CD40L promoted differentiation towards the M1 spectrum and repolarization of M2
      spectrum macrophages towards the M1 spectrum phenotype. Treatment of in vitro co
      cultures of T and B cells with HERA-CD40L-triggered robust antitumor activation
      of T cells, which depended upon direct interaction with B cells. In contrast,
      bivalent anti-CD40 antibodies and trivalent soluble CD40L displayed weak activity
      which critically depended on crosslinking. In vivo, a murine surrogate of HERA
      CD40L-stimulated clonal expansion of OT-I-specific murine CD8 T cells and showed
      single agent antitumor activity in the CD40 syngeneic MC38-CEA mouse model of
      colorectal cancer, suggesting an involvement of the immune system in controlling
      tumor growth. We conclude that HERA-CD40L is able to establish robust antitumor
      immune responses both in vitro and in vivo.

PMID- 30273199
TI  - Trends of Polypharmacy and Prescription Patterns of Antidepressants in Asia.
AB  - PURPOSE: Little is known regarding the trend of polypharmacy in Asia. We used
      data from 5 Asian countries to examine the patterns of antidepressant (AD)
      prescription and trends of psychotropic polypharmacy over time. METHODS: We used
      the cross-sectional, pharmacoepidemiological data from 2004 and 2013 REAP-AD
      (Research on Asian Psychotropic Prescription Patterns for Antidepressants) to
      examine the patterns of AD prescriptions in clinical settings in China, Japan,
      Korea, Singapore, and Taiwan. We compared the trend in polypharmacy (ie,
      concomitant use of >=2 classes of psychotropic) among individuals receiving AD
      prescriptions in 2004 and 2013 using multivariable logistic regression models in
      different diagnostic categories. RESULTS: The proportion of patients with
      psychotropic polypharmacy decreased from 2004 to 2013 in all 3 diagnostic
      categories, including mood disorders (adjusted odds ratio [aOR], 0.44 [0.35
      0.56]; P < 0.001), anxiety disorders (aOR, 0.58 [0.36-0.94]; P = 0.028), and
      psychotic disorders (aOR, 0.18 [0.05-0.60]; P = 0.006). Among individuals with AD
      prescriptions, concomitant use of anxiolytics (including sedative-hypnotics)
      decreased in patients with mood disorders (aOR, 0.34 [0.27-0.42]; P < 0.001) and
      anxiety disorders (aOR, 0.43 [0.27-0.67]; P < 0.001). In contrast, concomitant
      use of antipsychotics in patients with mood disorders increased (aOR, 1.43 [1.15
      1.77]; P = 0.001), and concomitant use of mood stabilizers in patients with
      psychotic disorders also increased (aOR, 3.49 [1.50-8.14]; P = 0.004).
      CONCLUSIONS: This is the first study examining trends in psychotropic
      polypharmacy in East Asia. We found a generally decreasing trend of psychotropic
      polypharmacy in contrast to the increasing trend reported from Western countries.
      These findings could offer significant implications for health system reform or
      policy making.

PMID- 30273200
TI  - The Effect of Ultra-low-dose Intrathecal Naloxone on Pain Intensity After Lumbar
      Laminectomy With Spinal Fusion: A Randomized Controlled Trial.
AB  - BACKGROUND: Despite advances in pain management, several patients continue to
      experience severe acute pain after lumbar spine surgery. The aim of this study
      was to assess the safety and effectiveness of single ultra-low-dose intrathecal
      (IT) naloxone in combination with IT morphine for reducing pain intensity,
      pruritus, nausea, and vomiting in patients undergoing lumbar laminectomy with
      spinal fusion. MATERIALS AND METHODS: In this double-blind trial, patients
      scheduled for lumbar laminectomy with spinal fusion were randomly assigned to
      receive single ultra-low-dose IT naloxone (20 MUg) and IT morphine (0.2 mg)
      (group M+N) or IT morphine (0.2 mg) alone (group M). The severity of
      postoperative pain, pruritus and nausea, and frequency of vomiting were assessed
      at recovery from anesthesia and, subsequently, at 1, 3, 6, 12, and 24 hours
      postoperatively using an 11-point (0-10) visual analogue scale. RESULTS: A total
      of 77 patients completed the study, and there were significant differences in
      postoperative pain, pruritus, and nausea visual analogue scale between the groups
      (P<0.05). After adjusting for body mass index and surgery duration, IT naloxone
      administration reduced the pain score (coefficient=1.84; 95% confidence interval
      [CI], 1.05-2.63; P<0.001), and the scores of pruritus and nausea
      (coefficient=0.9; 95% CI, 0.44-1.37; P<0.001 and coefficient=0.71; 95% CI, 0.12
      1.31; P=0.02, respectively) compared with IT morphine alone. No serious adverse
      effects were observed. CONCLUSIONS: The addition of ultra-low-dose IT naloxone to
      IT morphine provides excellent postoperative pain management and effectively
      controls pruritus and nausea in patients undergoing laminectomy with spinal
      fusion.

PMID- 30273201
TI  - A Survey On Fever Monitoring and Management in Patients With Acute Brain Injury:
      The SUMMA Study.
AB  - BACKGROUND: Fever is common in patients with acute brain injury and worsens
      secondary brain injury and clinical outcomes. Currently, there is a lack of
      consensus on the definition of fever and its management. The aims of the survey
      were to explore: (a) fever definitions, (b) thresholds to trigger temperature
      management, and (c) therapeutic strategies to control fever. MATERIALS AND
      METHODS: A questionnaire (26 items) was made available to members of the European
      Society of Intensive Care Medicine via its website between July 2016 and December
      2016. RESULTS: Among 231 respondents, 193 provided complete responses to the
      questionnaire (84%); mostly intensivists (n=124, [54%]). Body temperature was
      most frequently measured using a bladder probe (n=93, [43%]). A large proportion
      of respondents considered fever as a body temperature >38.3 degrees C (n=71,
      [33%]). The main thresholds for antipyretic therapy were 37.5 degrees C (n=74,
      [34%]) and 38.0 degrees C (n=86, [40%]); however, lower thresholds (37.0 to 37.5
      degrees C) were targeted in cases of intracranial hypertension and cerebral
      ischemia. Among first-line methods to treat fever, ice packs were the most
      frequently utilized physical method (n=90, [47%]), external nonautomated system
      was the most frequent utilized device (n=49, [25%]), and paracetamol was the most
      frequently utilized drug (n=135, [70%]). Among second-line methods, intravenous
      infusion of cold fluids was the most frequently utilized physical method (n=68,
      [35%]), external computerized automated system was the most frequently utilized
      device (n=75, [39%]), and diclofenac was the most frequently utilized drug (n=62,
      [32%]). Protocols for fever control and shivering management were available to 83
      (43%) and 54 (28%) of respondents, respectively. CONCLUSIONS: In this survey we
      identified substantial variability in fever definition and application of
      temperature management in acute brain injury patients. These findings may be
      helpful in promoting educational interventions and in designing future studies on
      this topic.

PMID- 30273202
TI  - Quality and Safety in Health Care, Part XLVI: Mindfulness, Meditation, and
      Burnout.
AB  - Some of the approaches to prevent and recover from burnout focus on the
      individual, and others focus on organizational initiatives. A common
      recommendation for the individual with burnout is to practice meditation and
      mindfulness. Mindfulness may be defined as focused awareness without judgment
      regarding the current instance in time. The practice of mindfulness and the
      outcome of various mindfulness courses will be discussed in this article. Other
      approaches on the subject of burnout regarding individual efforts and
      organizational changes will be discussed in subsequent articles in this series.

PMID- 30273203
TI  - Unraveling the Cause of Anuria Post Kidney Transplantation by Renal Scintigraphy.
AB  - A dynamic renal scintigraphy is widely used after renal transplantation to
      evaluate transplant function and possible complications. We report the case of a
      27-year-old man with persisting anuria after kidney transplantation. A renal
      scintigraphy using Tc-ethylenedicysteine followed by SPECT/CT of the abdomen was
      performed showing tracer accumulation in the colon without any activity in the
      bladder, as a result of ureter reimplantation onto the sigmoid instead of onto
      the previously reconstructed bladder. Renal scintigraphy identified the cause and
      localization of the urinary leak, which led to immediate surgical reimplantation
      of the ureter onto the augmented bladder with onset of diuresis.

PMID- 30273204
TI  - 68Ga-PSMA-11 PET/CT in Newly Diagnosed Prostate Adenocarcinoma.
AB  - INTRODUCTION: Prostate-specific membrane antigen (PSMA) ligand PET/CT is an
      emerging modality to detect the metastatic disease, especially in intermediate-
      and high-risk prostate cancer (PCa). In this study, we analyzed the contribution
      of Ga-PSMA-11 PET/CT in staging and therapy management of newly diagnosed PCa.
      MATERIALS AND METHODS: A total of 78 patients with biopsy-proven PCa who were
      referred for Ga-PSMA-11 PET/CT for primary staging were retrospectively analyzed.
      The patients were divided into risk groups according to the D'Amico risk
      stratification criteria. All of the patients had undergone pelvic MRI, and 65
      patients had bone scintigraphy also. The findings of Ga-PSMA-11 PET/CT were
      compared with these conventional imaging (CI) methods for staging of the disease.
      The relations between SUVmax of the primary tumors and Gleason scores (GSs),
      prostate-specific antigen (PSA) levels, and metastatic extent of the disease were
      analyzed. RESULTS: Of 78 patients, 5 patients were in low-risk group, 18 patients
      were in intermediate-risk group, and 55 patients were in high-risk group.
      Metastatic disease was found in 40 (51.2%) of 78 patients in Ga-PSMA-11 PET/CT.
      Ten patients had regional lymph node metastases, and 30 patients had distant
      metastases. Ga-PSMA-11 PET/CT changed the staging in 44 (56.4%) of 78 patients
      compared with CI. There was significant difference between the SUVmax of the
      tumors with GSs of 6 and 7 compared with GSs of 8, 9, and 10 (P = 0.003). The
      SUVmax were significantly different between the patients with no metastasis (n =
      38) and patients with regional lymph node metastases or distant metastases (n =
      40; 16.1 +/- 10.9, 28.7 +/- 25.8, P = 0.003, respectively). There was significant
      difference between the SUVmax of patients with PSA level less than 10 ng/mL
      compared with patients with PSA level of 10 or greater and less than 20 ng/mL and
      PSA 20 ng/mL or greater (P = 0.009). A weak correlation between PSA and primary
      tumor SUVmax was also found (r = 0.21). CONCLUSIONS: Ga-PSMA-11 PET/CT is an
      important imaging modality for primary evaluation of newly diagnosed PCa changing
      the disease stage substantially. Also the SUVmax of the primary tumor has a
      relation with GS, metastatic extent of disease, and PSA levels defining the
      prognosis.

PMID- 30273205
TI  - Pretreatment Primary Tumor and Nodal SUVmax Values on 18F-FDG PET/CT Images
      Predict Prognosis in Patients With Salivary Gland Carcinoma.
AB  - PURPOSE: To assess whether primary tumor and nodal F-FDG uptake may predict
      prognosis in patients with salivary gland carcinoma. METHODS: We conducted a 2
      center, retrospective study on 117 patients with salivary gland carcinoma who
      underwent F-FDG PET/CT before treatment and were subsequently treated with
      curative intent between 2004 and 2014. Pretreatment SUVmax of the primary tumor
      (SUVmax-T) and that of positive nodes (SUVmax-N) were analyzed in relation to
      clinical outcomes. RESULTS: Patients were followed up for a median of 61 months.
      The following 5-year rates were observed: locoregional control (LRC), 78%;
      distant metastasis-free survival (DMFS), 67%; progression-free survival (PFS),
      62%; and overall survival (OS), 68%. A cutoff value of 7.0 maximized the
      prognostic impact of both SUVmax-T and SUVmax-N for PFS. Compared with patients
      with SUVmax-T and SUVmax-N values below the optimal cutoff, those with SUVmax-T
      and SUVmax-N of 7 or greater showed less favorable 5-year LRC (P < 0.001 and P <
      0.001), DMFS (P < 0.001 and P < 0.001), PFS (P < 0.001 and P < 0.001), and OS (P
      < 0.001 and P < 0.001) rates. Both SUVmax-T of 7 or greater and SUVmax-N of 7 or
      greater were identified as independent predictors of LRC (P = 0.010 and 0.022),
      DMFS (P = 0.001 and P = 0.001), PFS (P < 0.001 and P = 0.007), and OS (P = 0.007
      and P = 0.002) in multivariable analysis. We therefore devised a prognostic
      scoring system based on these 2 variables, which was found to be strongly
      associated with 5-year LRC (P < 0.001), DMFS (P < 0.001), PFS (P < 0.001), and OS
      (P < 0.001) rates. CONCLUSIONS: SUVmax of the primary tumor and SUVmax-N on
      pretreatment F-FDG PET/CT images may be a useful guide in predicting treatment
      outcomes, especially when combined in a prognostic scoring system.

PMID- 30273206
TI  - Increased Activity Due to Fractures Does Not Significantly Affect the Accuracy of
      68Ga-DOTATATE PET/CT in the Detection of Culprit Tumor in the Evaluation of Tumor
      Induced Osteomalacia.
AB  - OBJECTIVE: Ga-DOTATATE PET/CT is currently the most common imaging modality in
      localizing culprit tumors, which can result in tumor-induced osteomalacia (TIO).
      Fracture, which is one of the most common consequences of the TIO, can also lead
      to increased Ga-DOTATATE activity and potentially affect the accuracy of Ga
      DOTATATE PET/CT imaging. The aim of this investigation is to evaluate whether the
      increased Ga-DOTATATE activity at the sites of the fracture will cause
      interpretation difficulty in the localizing the culprit tumor causing TIO.
      METHOD: The images of Ga-DOTATATE PET/CT scan from a total of 54 patients who had
      multiple foci of increased Ga-DOTATATE PET/CT on PET/CT were retrospectively
      analyzed. Not only was the intensity of the activity on PET but also the
      appearance of the activity on CT taken into consideration when the interpretation
      of the images occurred. The results from imaging analysis were compared with the
      clinical chart record. All patients had tentative clinical diagnosis of TIO.
      RESULTS: The causative tumors in 53 patients were eventually identified. In 1
      patient, the causative tumor was not identified. Among the 53 patients with
      confirmed TIO, 52 tumors were accurately localized. CONCLUSIONS: Mild activity at
      the sites of fracture is not a major challenging factor in the interpretation of
      Ga-DOTATATE PET/CT in the evaluation of TIO when both intensity on PET and
      morphology on CT were assessed.

PMID- 30273207
TI  - Incidental Detection of Skeletal Metastases on 99mTc-DTPA Renography.
AB  - We present the case of a 53-year-old man with left hydroureteronephrosis who
      underwent Tc-DTPA renography for functional assessment of bilateral kidneys. Tc
      DTPA renography of the patient showed diffusely increased extrarenal Tc-DTPA
      uptake in the visualized lumbosacral vertebrae and in the pelvic bones, on the
      blood flow and functional phase of the renography, which was suggestive of
      disseminated skeletal disease. Subsequent MRI lumbosacral spine and F-FDG PET/CT
      revealed extensive skeletal metastases corresponding to the increased extrarenal
      Tc-DTPA uptake in the lumbosacral vertebrae and the pelvic bones from primary
      left lung mitotic lesion.

PMID- 30273208
TI  - 18F-FDG PET/CT in Isolated Primary Extraskeletal Osteosarcoma.
AB  - Extraskeletal osteosarcoma is a rare, high-grade soft tissue malignancy,
      accounting for approximately 1% of all soft tissue sarcomas. Despite the
      histologic resemblance to osteogenic osteosarcoma, it is considered as a distinct
      entity because of the differences in clinical behavior and response to treatment.
      Hence, imaging plays a vital role in establishing the nonskeletal origin of the
      tumor, differentiating it from osteogenic osteosarcoma. We present F-FDG PET/CT
      findings in a case of isolated primary extraskeletal osteosarcoma confirmed on
      histopathology.

PMID- 30273209
TI  - Benign Esophageal Findings on 68Ga-Prostate-Specific Membrane Antigen PET/CT
      Scan.
AB  - In 2 high-risk prostate cancer patients, PET scans revealed focally increased Ga
      prostate-specific membrane antigen uptake in the distal esophagus. Both patients
      had hiatus herniation on gastroscopy, and esophageal biopsies revealed acute and
      chronic inflammation in both patients and a benign hyperplastic polyp in one of
      the patients. Recently, reports have demonstrated that inflammation can cause
      false-positive findings on Ga-prostate-specific membrane antigen PET/CT, and
      these cases present this phenomenon in the esophagus as well.

PMID- 30273210
TI  - Reply to lung ultrasound for the diagnosis of pneumonia.

PMID- 30273211
TI  - DCCN Appoints Dr Brigitte Cypress to the Editorial Board.

PMID- 30273212
TI  - Oral Care Protocols With Specialty Training Lead to Safe Oral Care Practices and
      Reduce Iatrogenic Bleeding in Extracorporeal Membrane Oxygenation Patients.
AB  - INTRODUCTION: Oral care, using either a mouth rinse, gel, toothbrush, or
      combination of them, together with aspiration of secretions, may reduce the risk
      of ventilator-acquired pneumonia in intubated patents. Oral care procedure in
      patients on venovenous extracorporeal membrane oxygenation (VV-ECMO) may cause
      bleeding due to the systemic anticoagulation required. PURPOSE: The aim of this
      study was to investigate the rate of bleeding episodes during oral care in
      patients supported by VV-ECMO. METHODS: A retrospective observational study was
      performed. All patients admitted to an Italian ECMO center during 2014 were
      included in the study. RESULTS: Data from 14 patients were analyzed. The median
      intensive care unit length of stay was 39.0 days (interquartile range, 27.3-83.3
      days), and median days on VV-ECMO was 19.5 (10.3-46.0). There were 440 ECMO days,
      with 1320 oral care maneuvers. In 7 patients, bleeding episodes occurred: 2 with
      orotracheal intubation and 5 initially managed with orotracheal intubation,
      thereafter via Translaryngeal tracheostomy tube (according to Fantoni's
      technique). In 61 oral care procedures (4.6%), bleeding was detected during or
      after the maneuver, whereas the total numbers of days with at least 1 bleeding
      episode were 35 (8%).The presence or absence of bleeding during ECMO days was
      statistically significant for international normalized ratio (1.01 [0.95-1.11] vs
      1.13 [1.03-1.25], P < .0001), platelets (163 000 [93 500-229 000] vs 61 000 [91
      00-100 000], P < .0001), and mouth care score (6 [5-7] vs 8 [7-9], P < .001).
      CONCLUSION: Oral care can cause bleeding in patients on VV-ECMO. Implementation
      of protocols for daily oral care in patients on ECMO may reduce risks. As
      recommended by the literature, this category of patients should be treated in
      selected centers distinguished by a regular volume of ECMO activity and the
      presence of dedicated ECMO specialist nurses.

PMID- 30273214
TI  - 2018 Guide to Nursing Certification Boards.
AB  - Nursing specialty certification is a way to demonstrate clinical and professional
      growth. Use this resource to learn about available certifications and contact the
      certifying body that meets your needs.

PMID- 30273215
TI  - Qualitative Research Methods: A Phenomenological Focus.
AB  - Data collection and management are often neglected subjects of qualitative
      research. Qualitative data collection, management, and analysis are complex and
      challenging for researchers especially for early career and doctoral students.
      These processes involve anticipating for ethical issues and developing means and
      methods for collecting, recording, and storing data securely. Approaches to data
      analysis include organizing, reading, coding, and organizing themes,
      representing, and interpreting the data. The unanticipated issues in
      accomplishing these steps and corresponding solutions are presented.
      Recommendations for training and mentoring of novices in qualitative research are
      discussed.

PMID- 30273216
TI  - Impact of a Nurse Intervention to Improve Sleep Quality in Intensive Care Units:
      Results From a Randomized Controlled Trial.
AB  - BACKGROUND: Patients of adult intensive care units (ICUs) often suffer from a
      lack of sleep. Reducing anxiety by promoting adaptation to the ICU prior to
      admission may be an appropriate way to increase sleep quality. OBJECTIVE: The aim
      of this study was to evaluate the impact on sleep quality of a brief nurse
      intervention. METHODS: This was a pilot randomized controlled trial in Spain.
      Forty patients admitted in hospital for valve cardiac surgery were randomly
      allocated to (1) control group (n = 20), receiving usual care, and to (2)
      experimental group (EG, n = 20), receiving a nurse intervention the day before
      surgery and admission in the ICU. The intervention was based on Roy Adaptation
      Model. A trained nurse anticipated the stressful stimulus to patients in order to
      develop functional adaptive behaviors. A set of photographs and videos was used
      to illustrate the environment and assistance in the ICU. Sleep quality in the ICU
      was measured with the Richards-Campbell Sleep Questionnaire and usual sleep
      quality with the Pittsburgh Sleep Quality Index. RESULTS: After the intervention,
      sleep quality was lower in the EG compared with the control group (-4 points in
      Richards-Campbell Sleep Questionnaire, P = .69). Adjustment for main confounders
      led this reduction to -1.9 points (P = .87) among patients in EG. Stratified
      analyses shown a positive impact for people who usually slept well (+5.2 points,
      P = .77), but negative for those who had previous poor sleep quality (-20.0
      points, P = .24). CONCLUSION: A nurse intervention prior to ICU admission did not
      increase patients' sleep quality. In addition, the intervention could have
      incremented anxiety over the patients who used to sleep poorly at their homes.

PMID- 30273219
TI  - Thank You, DCCN Peer Reviewers 2017-2018.

PMID- 30273218
TI  - Nurse-Initiated Mobilization Practices in 2 Community Intensive Care Units: A
      Pilot Study.
AB  - BACKGROUND: Critical-care nurses play a vital role in promoting safe early
      mobilization in intensive care unit (ICU) settings to reduce the risks associated
      with immobility in ICUs, including the risk of delirium, ICU-acquired weakness,
      and functional decline. OBJECTIVE: The purposes of this study were to describe
      nurse-led mobilization practices in 2 community hospital ICUs and to report
      differences and similarities between the 2 settings. METHODS: This was a cross
      sectional exploratory study of 18 nurses (ICU A: n = 12, ICU B: n = 6) and 124
      patients (ICU A: n = 50, ICU B: n = 74). Patient-specific therapeutic
      intervention needs and nurse-initiated mobilization practices were tracked over a
      1-month period. RESULTS: Differences in patient characteristics and nurse-led
      mobilization activities were observed between ICUs. After controlling for patient
      characteristics, we found statistically significant differences in nurse-led
      mobilization activities between the 2 units, suggesting that factors other than
      patient characteristics may explain differences in nurse-led mobilization
      practices.

PMID- 30273220
TI  - Celebrating "What Matters" for the Holidays.

PMID- 30273221
TI  - Aquatic Orthopaedic Injuries.
AB  - Extremity injuries sustained in aquatic environments require unique
      considerations compared with injuries sustained on land. Knowledge of these
      considerations is becoming more important as aquatic recreational activities
      increase in popularity. Aquatic injuries may occur through mechanical contact
      with a variety of different objects or surfaces, such as a recreational device or
      watercraft part, or may occur through contact with marine animals. Marine animal
      injuries can be further categorized into bites, stings, or blunt contact, as well
      as venomous or nonvenomous, distinctions that should be used to guide clinical
      management. Numerous instances of retained foreign bodies after marine animal
      stings exist, which can result in infection and prolonged envenomization; thus,
      radiographic examination should be routinely performed in aquatic sting injuries
      to prevent these harmful sequelae. Any aquatic injury resulting in an open wound
      has an increased risk for infection, and prophylactic antibiotics must be given
      with consideration for the unique microbiologic flora of the aquatic environment.

PMID- 30273222
TI  - Arthroscopic Management of Glenohumeral Arthritis: A Joint Preservation Approach.
AB  - Treatment of young, active patients with primary glenohumeral osteoarthritis
      (GHOA) is challenging because shoulder arthroplasty may not be ideal in this
      population. In the past two decades, joint-preserving arthroscopic management
      options for GHOA, including debridement, have been used to treat different
      pathologies related to GHOA to reduce pain, to improve function, and to delay or
      even avoid arthroplasty. Key aspects of comprehensively addressing GHOA
      arthroscopically include chondroplasty, synovectomy, loose body removal, humeral
      osteoplasty with excision of the goat's beard osteophyte, capsular release,
      subacromial and subcoracoid decompression, axillary nerve decompression, and
      biceps tenodesis. Although data are still emerging, clinical studies report that
      an arthroscopic approach to glenohumeral arthritis using these various procedures
      reduces pain, improves function, and improves clinical outcome scores in the
      short- to mid-term follow-up period. Additional high-level studies are warranted
      to evaluate long-term outcomes and durability following this procedure.

PMID- 30273223
TI  - Testing between the gunpowder fuse and the filling-hose analogy for mental curve
      tracing using electroencephalography: boom!
AB  - Curve tracing occurs when a line is followed covertly to accomplish a task, for
      example, to determine whether two landmarks are on the same line or not (could
      Highway 61 take Robert Johnson from New Orleans to St Louis?). Previous work
      suggests that attention either moves along the curve, momentarily activating
      local representations of the curve during this process, leaving little or no
      trace of this activation once attention has passed, or attention spreads along
      the curve, resulting in an activated state along the entire portion of the curve
      that was traced. We re-examined this issue using event-related potentials. Curves
      to be traced were presented briefly to encourage a rapid deployment of attention.
      The curves started on the vertical midline and passed into the left or right
      visual field and terminated either on the vertical midline or at a lateral
      position. We measured a posterior contralateral negativity (relative to the
      visual field of the traced curve) that offset more rapidly when the curve was
      traced back to the midline than when it remained lateral. The results suggest
      that attention travels along the curve like fire on a fuse, with activation
      returning to baseline once the flame has passed.

PMID- 30273224
TI  - The endoplasmic reticulum stress transducer old astrocyte specifically induced
      substance positively regulates glial scar formation in spinal cord injury.
AB  - To investigate the relationship between endoplasmic reticulum (ER) stress
      mediated by old astrocyte specifically induced substance (OASIS) and astrogliosis
      in spinal cord injury (SCI). SCI models were established using adult male mice
      deficient for OASIS and C57BL/6 (wild-type mice) mice. After SCI, recovery and
      astrogliosis were examined in the mice at specific time points using functional
      and histological methods. After SCI, functional recovery was better in the OASIS
      deficient mice than in the wild-type mice. OASIS deletion did not inhibit
      astrocyte migration but reduced the excessive accumulation of N-cadherin
      expressing reactive astrocytes that formed the glial scar around the injury site.
      In addition, OASIS deletion increased the number of serotonin-positive axons in
      spinal cord regions caudal to the injury site. These findings suggested that the
      OASIS-mediated ER stress response inhibits the repair of the injured spinal cord
      by promoting the development of N-cadherin-expressing reactive astrocytes that
      form glial scars following injury. OASIS deletion inhibited the development of N
      cadherin-positive reactive astrocytes that form glial scars and promoted axon
      growth and functional recovery after SCI. These results suggest that the ER
      stress response mediated by OASIS could be a new target in the treatment of SCI.

PMID- 30273225
TI  - Testis Involvement in Neuroblastoma: Report of 3 Cases in the Turkish Pediatric
      Oncology Group-Neuroblastoma Study and Review of the Literature.
AB  - BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor of
      childhood. Primary and secondary testicular involvement is extremely uncommon in
      neuroblastoma. PROCEDURE: All children with neuroblastoma treated with the
      Turkish Pediatric Oncology Group (TPOG)-Neuroblastoma (NB) Study and who had
      testis involvement either at diagnosis or at relapse were retrospectively
      evaluated. A review of all cases with neuroblastoma and testis involvement in the
      literature was done. RESULTS: There were 3 children with NB documented to have
      involvement of the testis, 2 at diagnosis, 1 at recurrence, within the 559 cases
      (0.5%) treated with the Turkish Pediatric Oncology Group (TPOG)-Neuroblastoma
      Protocol. All had advanced stage. Two were infants. A total of 57 cases of
      testicular or paratesticular neuroblastoma have been reported in children, and
      most cases represent metastases as in the 3 cases in our series. CONCLUSIONS:
      Neuroblastoma should be considered in the differential diagnosis of testicular
      mass and work-up for neuroblastoma should be done before orchiectomy. Scrotal
      ultrasonography should be used as the first diagnostic tool and abdominal
      ultrasonography shall be done additionally. Testis examination should be
      performed at diagnosis and regularly during follow-up for boys diagnosed with
      neuroblastoma. Testes may be sanctuary sites when neuroblastoma is metastatic, as
      is the case in leukemia.

PMID- 30273226
TI  - Short article: Frequency, pathophysiology, and clinical classification of
      intestinal failure type II and III at a tertiary referral center.
AB  - OBJECTIVE: Intestinal failure (IF) is a complex disease that is gaining
      significance and attention throughout the world. In Mexico, there are no
      available data on this condition. The aim of this study was to determine the
      frequency and characteristics of patients with IF type II and III hospitalized at
      a tertiary referral center in our country. PATIENTS AND METHODS: A cross
      sectional study was carried out from August 2016 to July 2017. Adult patients
      hospitalized in noncritical areas with a recent diagnosis of IF type II or III
      according to the European Society for Clinical Nutrition and Metabolism
      classification were included. Demographic, anthropometric, nutritional therapy,
      biochemical, and clinical characteristics were registered. Nutritional risk was
      determined by the Nutritional Risk Score 2002. RESULTS: During the study, 4144
      patients were admitted to noncritical areas; 21 (5/1000) of these patients were
      included. The mean age of the patients was 51+/-18.8 years, and the mean BMI was
      17.6+/-5.5 kg/m. Fifteen (71.5%) patients were diagnosed with IF type II and six
      (28.5%) with IF type III. The primary diagnosis was surgical complications in
      seven (33.3%) of the cases and the principal pathophysiological mechanism was
      short bowel syndrome in nine (42.8%) patients. The most frequent (37%) clinical
      classification was D2: more than 20 kcal/kg/day and 1001-2000 ml/day and
      parenteral nutrition and PN2: 1001-2000 ml/day (52.3%) based on the modified
      European Society for Clinical Nutrition and Metabolism clinical classification.
      CONCLUSION: In this study, a high frequency of IF was found; surgical
      complications and short bowel syndrome were the main mechanisms involved, and D2
      was the most frequent clinical category.

PMID- 30273227
TI  - Dysregulation of the Inflammatory Mediators in the Multifidus Muscle After
      Spontaneous Intervertebral Disc Degeneration SPARC-null Mice is Ameliorated by
      Physical Activity.
AB  - STUDY DESIGN: A longitudinal case-control animal model. OBJECTIVE: The aim of
      this study was to investigate the inflammatory pathways active in the multifidus
      muscle after spontaneous intervertebral disc degeneration (IDD), and whether
      these IDD-related muscle changes can be ameliorated by exercise. SUMMARY OF
      BACKGROUND DATA: A pro-inflammatory response is present in the multifidus muscle
      after an intervertebral disc lesion and has been proposed to drive the structural
      alterations present during low back pain. However, it is not known whether
      spontaneous IDD produces an inflammatory response. Furthermore, exercise/physical
      activity produces a strong anti-inflammatory response, but its effectiveness in
      ameliorating inflammation in the multifidus is unknown. We assessed the
      inflammatory profile of the multifidus and the effectiveness of physical activity
      as a treatment using an animal model of spontaneous model of IDD. METHODS: Wild
      type and SPARC null mice that were sedentary or housed with a running wheel were
      used in this study. Multifidus muscle segments were harvested from L2-L6 from the
      mice at 9 months of age after they had undergone a magnetic resonance imaging
      (MRI) scan to determine levels with IDD. The inflammatory profile of the
      multifidus was examined using quantitative polymerase chain reaction (PCR)
      assays. RESULTS: Spontaneous IDD in the SPARC-null mice caused a dysregulation of
      interleukin (IL)-1beta, IL6, transforming growth factor-beta (TGFbeta1), and
      adiponectin expression. More specifically, the proximity and degree of IDD was
      related to levels of IL-1beta expression. Physical activity reduced the pro
      inflammatory response to IDD in the multifidus. IL-1beta, tumor necrosis factor
      (TNF), IL-10, adiponectin, and leptin levels were lower in the physically active
      group. CONCLUSION: These results reveal that spontaneous IDD causes dysregulation
      of the inflammatory pathways active in the multifidus muscle. These alterations
      were related to the severity of IDD and were prevented by physical activity.
      LEVEL OF EVIDENCE: N/A.

PMID- 30273228
TI  - Statistical Versus Clinical Significance in Subclavian Vein Cross-Sectional Area:
      Is a 0.10-cm2 Difference Really Meaningful or Just an Example of False Precision?

PMID- 30273229
TI  - Persistent Nociception Facilitates the Extinction of Morphine-Induced Conditioned
      Place Preference.
AB  - BACKGROUND: As opioid abuse and addiction have developed into a major national
      health crisis, prescription of opioids for pain management has become more
      controversial. However, opioids do help some patients by providing pain relief
      and improving the quality of life. To better understand the addictive properties
      of opioids under chronic pain conditions, we used a conditioned place preference
      (CPP) paradigm to examine the rewarding properties of morphine in rats with
      persistent nociception. METHODS: Spared nerve injury (SNI) model was used to
      induce persistent nociception in rats. Nociceptive behavior was assessed by von
      Frey test. CPP test was used to examine the rewarding properties of morphine.
      RESULTS: Our findings are as follows: (1) SNI rats did not show a difference
      compared with sham rats in magnitude of morphine-induced CPP 1 day after last
      morphine injection (2-way analysis of variance; for SNI versus sham, F[1,42] =
      0.014, P = .91; and 95% confidence intervals for difference of means, -5.9 [-58
      to 46], 0.76 [-51 to 53], and 0.90 [-51 to 53] for 2.5, 5, and 10 mg/kg,
      respectively); (2) increasing morphine dosage (2.5, 5, and 10 mg/kg) did not
      further increase the magnitude of CPP in both sham and SNI rats (for dosage:
      F[2,42] = 0.94, P = .40); and (3) morphine-induced CPP persisted in sham rats but
      extinguished in SNI rats when tested at 8 days after last morphine injection (for
      sham versus SNI: Bonferroni correction, P < .006 for both 5 and 10 mg/kg doses;
      and 95% confidence intervals for difference of means, 80.3 [19.7-141] and 87.0
      [26.3-148] for 5 and 10 mg/kg, respectively). CONCLUSIONS: Our data provide new
      evidence supporting the notion that the brain's reward circuitry changes in the
      context of persistent pain. This observational study suggests that future
      investigation into the neurobiology of opioid reward requires consideration of
      the circumstances in which opioid analgesics are administered.

PMID- 30273230
TI  - Grade 3 Echocardiographic Diastolic Dysfunction Is Associated With Increased Risk
      of Major Adverse Cardiovascular Events After Surgery: A Retrospective Cohort
      Study.
AB  - BACKGROUND: Diastolic dysfunction is common and may increase the risk of
      cardiovascular complications. This study investigated the hypothesis that, in
      patients with isolated left ventricular diastolic dysfunction, higher grade
      diastolic dysfunction was associated with greater risk of major adverse
      cardiovascular events (MACEs) after surgery. METHODS: This was a retrospective
      cohort study. Data of adult patients with isolated echocardiographic diastolic
      dysfunction (ejection fraction, >=50%) who underwent noncardiac surgery from
      January 1, 2015 to December 31, 2015 were collected. The primary end point was
      the occurrence of postoperative MACEs during hospital stay, which included acute
      myocardial infarction, congestive heart failure, stroke, nonfatal cardiac arrest,
      and cardiac death. The association between the grade of diastolic dysfunction and
      the occurrence of MACEs was assessed with a multivariable logistic model.
      RESULTS: A total of 2976 patients were included in the final analysis. Of these,
      297 (10.0%) developed MACEs after surgery. After correction for confounding
      factors, grade 3 diastolic dysfunction was associated with higher risk of
      postoperative MACEs (odds ratio, 1.71; 95% confidence interval, 1.28-2.27; P <
      .001) when compared with grades 1 and 2. Patients with grade 3 diastolic
      dysfunction developed more non-MACE complications when compared with grades 1 and
      2 (uncorrected odds ratio, 1.44; 95% confidence interval, 1.07-1.95; P = .017).
      CONCLUSIONS: In patients with isolated diastolic dysfunction undergoing
      noncardiac surgery, 10.0% develop MACEs during hospital stay after surgery; grade
      3 diastolic dysfunction is associated with greater risk of MACEs.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- 30273231
TI  - Clock Drawing Performance Slows for Older Adults After Total Knee Replacement
      Surgery.
AB  - BACKGROUND: Clock drawing is a neurocognitive screening tool used in preoperative
      settings. This study examined hypothesized changes in clock drawing to command
      and copy test conditions 3 weeks and 3 months after total knee arthroplasty (TKA)
      with general anesthesia. METHODS: Participants included 67 surgery and 66
      nonsurgery individuals >60 years who completed the digital clock drawing test
      before TKA (or a pseudosurgery date), and 3 weeks and 3 months postsurgery.
      Generalized linear mixed models assessed digital clock drawing test latency (ie,
      total time to completion, seconds between digit placement) and graphomotor output
      (ie, total number of strokes, clock size). Reliable change analyses examined the
      percent of participants showing change beyond differences found in nonsurgery
      peers. RESULTS: After adjusting for age, education, and baseline cognition, both
      digital clock drawing test latency measures were significantly different for
      surgery and nonsurgery groups, where the surgery group performed slower on both
      command and copy test conditions. Reliable change analyses 3 weeks after surgery
      found that total time to completion was slower among 25% of command and 21% of
      copy constructions in the surgery group. At 3 months, 18% of surgery participants
      were slower than nonsurgery peers. Neither graphomotor measure significantly
      changed over time. CONCLUSIONS: Clock drawing construction slowed for nearly one
      quarter of patients after TKA surgery, whereas nonsurgery peers showed the
      expected practice effect, ie, speed increased from baseline to follow-up time
      points. Future research should investigate the neurobiological basis for these
      changes after TKA.

PMID- 30273232
TI  - Pilot Survey of Female Anesthesiologists' Childbearing and Parental Leave
      Experiences.
AB  - While the literature regarding physicians' childbearing experiences is growing,
      there are no studies documenting those of anesthesiologists. We surveyed a
      convenience sample of 72 female anesthesiologists to obtain pilot data. Sixty-six
      women completed the survey (91.7% response rate), reporting 113 total births from
      before 1990 to present. Of all birth experiences, proportions of respondents
      reporting parental leave, lactation facilities, and lactation duration as
      adequate were 52.3%, 45.2%, and 58.3%, respectively. Most mothers (51.8%) gave
      birth to their first child while they were trainees. The majority (94.9%) favored
      an official statement supporting parental leave. These results may serve as
      groundwork for larger studies.

PMID- 30273233
TI  - Cutaneous adverse events of anti-programmed death 1 antibodies combined with anti
      cytotoxic T-lymphocyte-associated protein 4 therapy use in patients with
      metastatic melanoma.
AB  - To date, cutaneous toxicities of combination therapies of anti-programmed death-1
      (anti-PD1) and ipilimumab are poorly described. Understanding cutaneous
      presentations will aid clinicians with early diagnoses and treatments. We aim to
      describe and compare the cutaneous toxicities between the combination therapies
      and anti-PD1 monotherapy. This is a cohort study comparing previously published
      data on 82 patients with metastatic melanoma on anti-PD1 monotherapy, with a new
      group of 25 patients with metastatic melanoma receiving combined ipilimumab and
      pembrolizumab between January 2015 to February 2016. A single institution,
      internal referrals were received from medical oncology teams from May 2012 to
      February 2015 for the anti-PD1 monotherapy group and from January 2015 to
      February 2016 for combination group. All patients who were treated with either
      anti-PD1 therapy or combination therapies during the timeframe within the
      institution were included in the study. Kaplan-Meier curves were used to
      illustrate the time taken to develop cutaneous toxicities in the monotherapy and
      combination groups. Of the 25 patients, 88% developed new cutaneous lesions since
      the treatment. Immune-related lesions; lichenoid reaction (64%) and vitiligo
      (28%) were the most frequent. The incidence of lichenoid reaction increased
      rapidly in the early phase of treatment. Approximately one-third developed their
      first lichenoid reaction within 12 days of commencing treatment in combination
      group compared to 14 months in the anti-PD1 monotherapy. The rate of incidence of
      vitiligo was comparable in both groups. There was no statistical significance in
      the development of cutaneous toxicities and the treatment response between the
      two groups. The time taken to develop immune-related cutaneous toxicities was
      shorter for those on combination therapy versus anti-PD1 monotherapy.

PMID- 30273234
TI  - A practical approach to predict expansion of evidence networks: a case study in
      treatment-naive advanced melanoma.
AB  - Network meta-analysis (NMA) is a statistical method used to produce comparable
      estimates of efficacy across a range of treatments that may not be compared
      directly within any single trial. NMA feasibility is determined by the
      comparability of the data and presence of a connected network. In rapidly
      evolving treatment landscapes, evidence networks can change substantially in a
      short period of time. We investigate methods to determine the optimum time to
      conduct or update a NMA based on anticipated available evidence. We report the
      results of a systematic review conducted in treatment-naive advanced melanoma and
      compare networks of evidence available at retrospective, current, and prospective
      time points. For included publications, we compared the primary completion date
      of trials from clinical trials registries (CTRs) with the date of their first
      available publication to provide an estimate of publication lag. Using CTRs we
      were able to produce anticipated networks for future time points based on
      projected study completion dates and average publication lags which illustrated
      expansion and strengthening of the initial network. We found that over a snapshot
      of periods between 2015 and 2018, evidence networks in melanoma changed
      substantively, adding new comparators and increasing network connectedness.
      Searching CTRs for ongoing trials demonstrates it is possible to anticipate
      future networks at a certain time point. Armed with this information, sensible
      decisions can be made over when best to conduct or update a NMA. Incorporating
      new and upcoming interventions in a NMA enables presentation of a complete, up-to
      date and evolving picture of the evidence.

PMID- 30273236
TI  - The effect of the opioid epidemic on donation after cardiac death transplantation
      outcomes.
AB  - BACKGROUND: The opioid abuse epidemic and the deaths of otherwise healthy
      individuals due to drug overdose in the United States has major implications for
      transplantation. The current extent and safety of utilization of liver and kidney
      grafts from donation after cardiac death (DCD) donors who died in the context of
      opioid overdose is unknown. METHODS: Using national data from 2006 to 2016, we
      estimated the cumulative incidence of graft failure for recipients of DCD grafts,
      comparing the risk amongst recipients of organs from donors who died of anoxic
      drug overdose and recipients of organs from donors who died of other causes.
      RESULTS: One hundred and seventy-nine (6.2%) of 2908 liver graft recipients and
      944 (6.1%) of 15 520 kidney graft recipients received grafts from donors who died
      of anoxic drug overdose. Grafts from anoxic drug overdose donors were less
      frequently utilized compared to other DCD grafts (liver: 25.9% vs. 29.6%, 95% CI
      for difference, -6.7 to -0.7%; kidney: 81.0% vs. 84.7%; CI for difference, -7.3
      to -0.1%). However, the risk of graft failure at 5-years was similar for
      recipients of anoxic drug overdose donor grafts and recipients of other grafts
      (liver risk difference: 1.8% [95% CI, -7.8 to 11.8%], kidney risk difference: 
      1.5% [95% CI, -5.4 to 3.1%]). CONCLUSIONS: In the context of the current opioid
      epidemic, utilization of anoxic drug overdose DCD donor grafts does not increase
      the risk of graft failure and may help to address waitlist demands.

PMID- 30273238
TI  - Neuroinfectious Disease in Isolation.

PMID- 30273235
TI  - Kaposi sarcoma in HIV-positive solid organ transplant recipients: A French
      multicentric national study and literature review.
AB  - BACKGROUND: Kaposi sarcoma is a vascular tumor related to herpesvirus-8 and is
      promoted by immunosuppression. For the last 15 years, HIV patients have had
      access to organ transplantation. The dual immunosuppression of HIV and
      immunosuppressive treatments might increase the risk and severity of Kaposi
      sarcoma. METHODS: We conducted a multicentric retrospective study by collecting
      cases from French databases and society members of transplanted patients, among
      which 7 HIV-infected patients who subsequently developed Kaposi sarcoma were
      included. RESULTS: In the CRISTAL database (114 511 patients) and the DIVAT
      database (19 077 patients), the prevalence of Kaposi sarcoma was 0.18% and 0.46%,
      respectively, in transplanted patients; these values compare with 0.66% and
      0.50%, respectively, in transplanted patients with HIV. The median time from HIV
      infection to Kaposi sarcoma was 20 years. Kaposi sarcoma occurred during the
      first year after transplantation in most cases, while HIV viral load was
      undetectable. Only 2 patients had visceral involvement. Five patients were
      treated with conversion of calcineurin inhibitor to mTOR inhibitor, and 5
      patients were managed by decreasing immunosuppressive therapies. At 1 year, 4
      patients had a complete response, and 3 had a partial response. CONCLUSIONS: In
      our study, Kaposi sarcoma in transplanted patients with HIV did not show any
      aggressive features and was treated with the usual posttransplant Kaposi sarcoma
      management protocol.

PMID- 30273239
TI  - Acute Bacterial Meningitis.
AB  - PURPOSE OF REVIEW: While acute bacterial meningitis is becoming less common in
      developed countries because of the widespread use of vaccines against
      Streptococcus pneumoniae, Neisseria meningitides, and Haemophilus influenzae,
      bacterial meningitis still occurs worldwide, with peak incidence in young
      children and the elderly. Bacterial meningitis is usually lethal unless
      appropriate antibiotics that cross the blood-brain barrier are given. Clinical
      suspicion of bacterial meningitis begins when patients present with the abrupt
      onset of fever, headache, and meningismus. RECENT FINDINGS: New technologies are
      being developed for more rapid identification of the bacterial species causing
      meningitis. When appropriate, administration of adjunctive dexamethasone with the
      antibiotics often lessens neurologic sequelae in survivors, which may include
      aphasia, ataxia, paresis, hearing loss, and cognitive impairment. SUMMARY:
      Confirmation of the diagnosis of bacterial meningitis comes mainly from
      examination and culture of CSF obtained from a lumbar puncture. Typically, the
      CSF shows an elevated neutrophil count, elevated protein, depressed glucose,
      positive Gram stain, and growth of the bacteria on appropriate culture media.
      Antibiotic sensitivities of the bacteria determine the appropriate antibiotics,
      although an educated guess of the best antibiotics to be given promptly must be
      made until the antibiotic sensitivities return, usually in a few days.

PMID- 30273240
TI  - Viral Meningitis and Encephalitis.
AB  - PURPOSE OF REVIEW: This article discusses meningitis and encephalitis infections
      caused by viruses, excluding herpes family and human immunodeficiency virus
      (HIV). RECENT FINDINGS: The viral infections of the nervous system detailed in
      this article have no specific treatment other than supportive care. However, many
      of the viruses discussed are highly preventable by vaccination, proper skin
      protection against transmitting vectors, and postexposure prophylaxis. SUMMARY:
      While meningitis and encephalitis caused by viruses may have some clinical
      overlap, the management and outcomes can be highly disparate, making distinction
      between the two imperative. Furthermore, despite their relative rarity in terms
      of clinical disease, many of the viral infections discussed herein are highly
      preventable. Given the morbidity and mortality attached to such infections,
      provider and patient education are the best approach available to prevent these
      potentially devastating illnesses.

PMID- 30273241
TI  - Chronic Meningitis.
AB  - PURPOSE OF REVIEW: This article describes the clinical presentation, diagnostic
      approach (including the use of novel diagnostic platforms), and treatment of
      select infectious and noninfectious etiologies of chronic meningitis. RECENT
      FINDINGS: Identification of the etiology of chronic meningitis remains
      challenging, with no cause identified in at least one-third of cases. Often,
      several serologic, CSF, and neuroimaging studies are indicated, although novel
      diagnostic platforms including metagenomic deep sequencing may hold promise for
      identifying organisms. Infectious etiologies are more common in those at risk for
      disseminated disease, specifically those who are immunocompromised because of
      human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS),
      transplantation, or immunosuppressant medications. An important step in
      identifying the etiology of chronic meningitis is assembling a multidisciplinary
      team of individuals, including those with specialized expertise in ophthalmology,
      dermatology, rheumatology, and infectious diseases, to provide guidance regarding
      diagnostic procedures. SUMMARY: Chronic meningitis is defined as inflammation
      involving the meninges that lasts at least 4 weeks and is associated with a CSF
      pleocytosis. Chronic meningitis has numerous possible infectious and
      noninfectious etiologies, making it challenging to definitively diagnose
      patients. Therefore, a multifaceted approach that combines history, physical
      examination, neuroimaging, and laboratory analysis, including novel diagnostic
      platforms, is needed. This article focuses on key aspects of the evaluation of
      and approach to patients with chronic meningitis. Specific infectious etiologies
      and differential diagnoses of subacute and chronic meningitis, including
      noninfectious etiologies, are addressed.

PMID- 30273242
TI  - Brain and Spinal Epidural Abscess.
AB  - PURPOSE OF REVIEW: Brain abscesses and spinal epidural abscesses are serious,
      potentially life-threatening infections of the central nervous system. This
      article outlines the clinical presentation, evaluation, and management of brain
      abscesses and spinal epidural abscesses, with a specific focus on bacterial
      infections. RECENT FINDINGS: The overall incidence of brain abscesses has
      declined, in part because of fewer brain abscesses associated with otogenic
      infections. However, emerging patient populations at high risk for brain abscess
      include those with a history of penetrating head trauma, neurosurgery, or
      immunodeficiency. Improved mortality rates for brain abscess are attributable to
      modern diagnostic imaging, stereotactic-guided aspiration, and newer
      antimicrobials that readily penetrate into the central nervous system and
      abscesses. Brain MRI is more sensitive than CT for brain abscess, particularly in
      the early stages, but CT remains more widely available and can adequately
      identify potential abscesses and confirm response to treatment. With the advent
      of minimally invasive neurosurgical techniques, surgical excision is often
      employed only for posterior fossa, multiloculated, or superficial well
      circumscribed abscesses. In select clinical scenarios, conservative medical
      management may be a safe alternative to a combined surgical and medical approach.
      Unlike brain abscess, the incidence of spinal epidural abscess is on the rise and
      has been attributed to higher prevalence of predisposing factors, including
      spinal procedures and instrumentation. SUMMARY: Successful diagnosis and
      management of brain abscess and spinal epidural abscess requires a collaborative
      approach among neurologists, neurosurgeons, radiologists, and infectious disease
      physicians. The foundation of management of brain abscess includes surgical
      intervention for diagnostic purposes if a pathogen has not been identified or for
      decompression of larger abscesses or those with mass effect and significant
      surrounding edema; appropriate dosing and adequate duration of an antimicrobial
      regimen tailored to the presumptive source of infection and available culture
      data, and eradication of the primary source of infection. For spinal epidural
      abscesses, neurologic status at the time of presentation is directly related to
      outcomes, underscoring the importance of prompt recognition and intervention.

PMID- 30273243
TI  - Herpesvirus Infections of the Nervous System.
AB  - PURPOSE OF REVIEW: This article reviews the spectrum of neurologic disease
      associated with human herpesvirus infections. RECENT FINDINGS: As more patients
      are becoming therapeutically immunosuppressed, human herpesvirus infections are
      increasingly common. Historically, infections with human herpesviruses were
      described as temporal lobe encephalitis caused by herpes simplex virus type 1 or
      type 2. More recently, however, additional pathogens, such as varicella-zoster
      virus, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 have been
      identified to cause serious neurologic infections. As literature emerges,
      clinical presentations of herpesvirus infections have taken on many new forms,
      becoming heterogeneous and involving nearly every location along the neuraxis.
      Advanced diagnostic methods are now available for each specific pathogen in the
      herpesvirus family. As data emerge on viral resistance to conventional therapies,
      newer antiviral medications must be considered. SUMMARY: Infections from the
      herpesvirus family can have devastating neurologic outcomes without prompt and
      appropriate treatment. Clinical recognition of symptoms and appropriate advanced
      testing are necessary to correctly identify the infectious etiology. Knowledge of
      secondary neurologic complications of disease is equally important to prevent
      additional morbidity and mortality. This article discusses infections of the
      central and peripheral nervous systems caused by herpes simplex virus type 1 and
      type 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human
      herpesvirus 6. The pathophysiology, epidemiology, clinical presentations of
      disease, diagnostic investigations, imaging characteristics, and treatment for
      each infectious etiology are discussed in detail.

PMID- 30273244
TI  - Central Nervous System Infections Complicating Immunosuppression and
      Transplantation.
AB  - PURPOSE OF REVIEW: This article reviews infections associated with cancer
      treatments and immunosuppressive/immunomodulatory therapies used in both
      neoplastic and non-neoplastic conditions, including hematopoietic cell
      transplantation and solid organ transplantation. It provides a clinical approach
      to the most commonly affected patient groups based on clinicoanatomic
      presentation and disease-specific risks resulting from immune deficits and drugs
      received. RECENT FINDINGS: The clinical presentations, associated neuroimaging
      findings, and CSF abnormalities of patients with central nervous system
      infections who are immunocompromised may differ from those of patients with
      central nervous system infections who are immunocompetent and may be confused
      with noninfectious processes. Triggering of brain autoimmunity with emergence of
      neurotropic antibodies has emerged as a recognized parainfectious complication.
      New unbiased metagenomic assays to identify obscure pathogens help clinicians
      navigate the increasing range of conditions affecting the growing population of
      patients with altered immunity. SUMMARY: Despite evidence-based prophylactic
      regimens and organism-specific antimicrobials, central nervous system infections
      continue to cause significant morbidity and mortality in an increasing range of
      patients who are immunocompromised by their conditions and therapies. Multiple
      new drugs put patients at risk for progressive multifocal leukoencephalopathy,
      which has numerous imaging and clinical manifestations; patients at risk include
      those with multiple sclerosis, for whom infection risk is becoming one of the
      most important factors in therapeutic decision making. Efficient, early diagnosis
      is essential to improve outcomes in these often-devastating diseases.

PMID- 30273245
TI  - Neurologic Complications of Human Immunodeficiency Virus Infection.
AB  - PURPOSE OF REVIEW: Widespread use of antiretroviral therapy (ART) has led to near
      normal life expectancy in people with human immunodeficiency virus (HIV)
      infection. However, neurologic complications of HIV remain common; can affect any
      part of the neuraxis; and are due to direct effects of the virus,
      immunosuppression because of untreated HIV infection, aberrant immune responses
      in the setting of ART initiation, and ART toxicities. RECENT FINDINGS: HIV
      associated neurocognitive disorder (HAND) remains one of the most common
      neurologic complications of HIV encountered today, but milder forms predominate
      in people on ART. No specific treatments for HAND exist, but small trials and
      epidemiologic evidence suggest paroxetine, intranasal insulin, and maraviroc may
      have utility in its treatment; further trials of these agents are ongoing.
      Widespread ART use has decreased the incidence of central nervous system
      opportunistic infections, but prognosis often remains poor in those who develop
      opportunistic infections. High-titer positive serum cryptococcal antigen is
      strongly predictive of cryptococcal meningitis and provides a tool to enhance
      diagnosis in areas with limited resources. HIV is an independent risk factor for
      stroke, and accelerated aging associated with HIV infection results in neurologic
      diseases of older age occurring at much younger ages in individuals infected with
      HIV. Ongoing HIV replication in the CSF despite peripheral virologic suppression
      may contribute to the development of HAND and may not improve despite adjusting
      the ART regimen to increase central nervous system penetrance. SUMMARY:
      Neurologists are likely to encounter patients infected with HIV in clinical
      practice. This article reviews the presentation, diagnosis, and management of the
      most common neurologic conditions associated with HIV infection and ART.

PMID- 30273246
TI  - Tuberculosis of the Central Nervous System.
AB  - PURPOSE OF REVIEW: This article details the epidemiology and clinical
      manifestations of central nervous system (CNS) tuberculosis (TB), provides
      guidance for diagnostic imaging and CSF testing, and recommends treatment
      strategies for tuberculous meningitis and other forms of CNS TB, illustrating key
      aspects of diagnosis and management with case presentations. RECENT FINDINGS:
      Although improvements in our understanding of the pathogenesis and management of
      CNS TB have occurred over the past 50 years, the emergence of multidrug-resistant
      and extensively drug-resistant TB, the advent of acquired immunodeficiency
      syndrome (AIDS), and the subsequent availability of highly active antiretroviral
      therapy that can produce the immune reconstitution inflammatory syndrome have
      complicated the diagnosis and treatment of CNS TB. Advances in diagnostic assays
      promise to increase the speed of diagnosis as well as the percentage of people
      with a confirmed rather than a presumptive diagnosis. Advances in precision
      medicine have identified polymorphisms in the LTA4H gene that influence the risk
      for inflammation in patients with tuberculous meningitis. SUMMARY: CNS TB
      continues to be a major cause of morbidity and mortality, with the majority of
      people affected living in low-income and middle-income countries. Newer
      diagnostic assays promise to increase the speed of diagnosis and improve
      appropriate selection of antituberculous therapy and anti-inflammatory
      medications. Despite these advances, CNS TB remains difficult to diagnose, and
      clinicians should have a low threshold for initiating empiric therapy in patients
      with presumptive infection.

PMID- 30273247
TI  - Neuroborreliosis and Neurosyphilis.
AB  - PURPOSE OF REVIEW: This article presents an overview of the current diagnosis and
      management of two spirochetal infections of the nervous system, neuroborreliosis
      (Lyme disease) and neurosyphilis, focusing on similarities and differences.
      Although neuroborreliosis was first identified almost a century ago, much
      confusion remains about how to accurately diagnose this quite treatable nervous
      system infection. Well-established diagnostic tools and therapeutic regimens
      exist for neurosyphilis, which has been well-known for centuries. RECENT
      FINDINGS: Serologic testing targeting the C6 antigen may simplify diagnostic
      testing in neuroborreliosis while improving accuracy. Historically, screening for
      syphilis has used a reaginic test followed by a treponeme-specific assay;
      alternative approaches, including use of well-defined recombinant antigens, may
      improve sensitivity without sacrificing specificity. In neuroborreliosis,
      measurement of the chemokine CXCL13 in CSF may provide a useful marker of disease
      activity in the central nervous system. SUMMARY: Lyme disease causes meningitis,
      cranial neuritis, radiculitis, and mononeuropathy multiplex. Cognitive symptoms,
      occurring either during (encephalopathy) or after infection (posttreatment Lyme
      disease syndrome) are rarely, if ever, due to central nervous system infection.
      Posttreatment Lyme disease syndrome is not antibiotic responsive. Syphilis causes
      meningitis, cranial neuritis, chronic meningovascular syphilis, tabes dorsalis,
      and parenchymal neurosyphilis. The organism remains highly sensitive to
      penicillin, but residua of chronic infection may be irreversible.

PMID- 30273248
TI  - Tetanus, Botulism, and Diphtheria.
AB  - PURPOSE OF REVIEW: This article reviews the pathophysiology, epidemiology,
      clinical manifestations, diagnosis, and treatment of tetanus, botulism, and
      diphtheric neuropathy. RECENT FINDINGS: Tetanus is most common in lower-income
      settings, but rare cases are seen in higher-income settings because of the
      inadequate maintenance of vaccination status. Foodborne botulism remains rare,
      but botulism can also be caused by IV drug use (wound botulism) and medical use
      of botulinum toxin (iatrogenic botulism); botulinum toxin has also been
      considered a potential agent of bioterrorism. Diphtheric neuropathy is rare but
      has been seen in recent epidemics in the former Soviet Union, and vaccination
      status is inadequate in a significant proportion of older individuals, creating
      the potential for subsequent epidemics. SUMMARY: Tetanus, botulism, and
      diphtheric neuropathy are rare in higher-resource settings where most
      neurologists practice; however, familiarity with the unique clinical
      manifestations of and laboratory evaluation for these disorders is essential for
      the rapid diagnosis and treatment of patients with these conditions.

PMID- 30273249
TI  - Helminthic Infections of the Central Nervous System.
AB  - PURPOSE OF REVIEW: This article discusses select helminthic parasitic infections
      that may affect the central nervous system and reviews the epidemiology,
      neurologic presentation, recommended diagnostic testing, and treatment approach
      to these infections. RECENT FINDINGS: Emigration from and travel to areas endemic
      for helminthic infections that affect the nervous system has led to increased
      incidence of parasitic neurologic disease in developed countries, necessitating
      that neurologists be familiar with the diagnostic and therapeutic approach to
      these diseases. Evidence is emerging on the optimal treatment for
      neurocysticercosis, which varies based on the form of the disease in the nervous
      system. SUMMARY: Parenchymal neurocysticercosis is a leading cause of acquired
      epilepsy worldwide, and extraparenchymal neurocysticercosis is responsible for
      many cases of hydrocephalus. Recognition of the different stages and locations of
      neurocysticercosis is essential for proper management. Similarly, schistosomiasis
      constitutes a major cause of myelopathy in endemic areas and requires prompt
      diagnosis and treatment to avoid permanent deficits.

PMID- 30273250
TI  - Zika Virus and Other Emerging Arboviral Central Nervous System Infections.
AB  - PURPOSE OF REVIEW: In recent years, we have observed the emergence and
      reemergence of a number of arthropod-borne viruses (arboviruses). Zika virus is
      the most recent addition to this group, first causing sporadic cases of
      uncomplicated febrile illness followed by sizeable outbreaks in the Pacific.
      However, the epidemiology and clinical features of Zika virus infection have
      changed rapidly and dramatically; it is now recognized as causing Guillain-Barre
      syndrome (GBS) in children and adults and congenital abnormalities in infected
      fetuses. This article reviews the epidemiology, clinical features, and diagnosis
      of Zika virus-associated neurologic illness and briefly reviews features of West
      Nile virus and Japanese encephalitis virus. RECENT FINDINGS: Zika virus has
      emerged as a significant human pathogen in recent years. In 2015, it began to
      cause large outbreaks of febrile rash illness in South America and the Caribbean.
      During these large Zika virus outbreaks, a significant increase in the incidence
      of GBS was also observed in multiple countries/territories. Zika virus-associated
      GBS has several unique features, including a relatively short interval between
      febrile illness and GBS onset, an unusually high incidence among older people,
      and prominent cranial nerve abnormalities. Congenital Zika syndrome includes a
      myriad of abnormalities, including microcephaly, lissencephaly, hydrocephalus,
      arthrogryposis, and parenchymal calcifications. Currently, no treatment has been
      identified for Zika virus, although work on vaccines is under way. SUMMARY:
      Arboviruses continue to surprise us with unexpected emergence in various
      locations, the nature of clinical illness, and outcomes. Zika virus presents a
      classic example of this type of emergence. Ongoing surveillance will be needed to
      evaluate the long-term pattern of Zika virus and related arboviruses.

PMID- 30273255
TI  - Learning Objectives and Core Competencies.

PMID- 30273251
TI  - Legal and Ethical Considerations of Disclosing Human Immunodeficiency Virus
      Seropositivity to a Surrogate Decision Maker.
AB  - Ethical and legal issues arise when a patient who is human immunodeficiency virus
      (HIV) positive lacks decision-making capacity and the HIV status must be
      disclosed to a surrogate decision maker to allow for informed medical decision
      making. This article discusses the special exceptions to confidentiality built
      into the Health Insurance Portability and Accountability Act privacy protections,
      the limitations on claims of common-law marriage, and public health laws that
      often require informing individuals who are either sex partners or needle-sharing
      partners of newly diagnosed HIV-infected individuals that they have been exposed
      to HIV infection.

PMID- 30273256
TI  - Is the National Institutes on Alcohol and Alcoholism Screening Guide Useful for
      Identifying Adolescents at Risk for Later Cigarette Smoking? A Prospective Study
      in Primary Care Clinics.
AB  - OBJECTIVES: This paper evaluated whether a 2-item assessment of alcohol use risk,
      developed by the National Institute on Alcohol Abuse and Alcoholism (NIAAA SG),
      prospectively predicted smoking status among a sample of adolescents visiting
      their primary care physician. METHODS: We analyzed a sample of 651 adolescents
      (57.80% female; 56.53% Hispanic, 22.73% African American, 14.44% White, 6.30%
      other) who completed the NIAAA SG at a baseline appointment and were assessed for
      future smoking risk. We obtained prospective data on smoking status using data
      from the 6-month post-baseline follow-up assessment. RESULTS: Logistic regression
      analyses revealed that adolescents who were identified as at risk by the NIAAA SG
      were more likely to report smoking within 6 months. However, the association
      between the NIAAA SG and future smoking status became non-significant after
      controlling for future smoking risk measured at baseline. CONCLUSIONS: Questions
      that ask about past smoking and future smoking intentions are best used to screen
      adolescents in primary care for smoking risk.

PMID- 30273257
TI  - Psychosocial Adjustment and Quality of Life in Patients With Peripartum
      Cardiomyopathy.
AB  - BACKGROUND: Psychological distress can adversely affect heart failure prognosis,
      yet the immediate and ongoing challenges faced by women diagnosed with peripartum
      cardiomyopathy (PPCM) are not well studied. OBJECTIVE: We examined psychological
      distress and quality of life in a large, national sample of patients with PPCM
      and evaluated whether these characteristics differ among newly diagnosed (0-1
      year), short-term (2-4 years), and long-term (5-10 years) survivors. METHODS: One
      hundred forty-nine patients with PPCM (mean age, 33.9 +/- 5.0 years) recruited
      from a web-based registry completed questionnaires about generalized anxiety
      (Generalized Anxiety Disorder-7), cardiac anxiety (Cardiac Anxiety Questionnaire
      [CAQ]), health status (Medical Outcomes Study Short-Form 12 [SF-12] Health
      Survey), and PPCM-specific quality-of-life concerns. Group differences were
      evaluated using multivariate statistics with adjustments for disease severity and
      psychiatric history. RESULTS: Generalized anxiety symptoms higher than the
      clinical cutoff were reported by 53% of patients with PPCM. Mean scores on the
      CAQ (1.9 +/- 0.7) and CAQ subscale scores (cardiac-specific fear [2.1 +/- 0.8],
      avoidance [1.7 +/- 0.9], and heart-focused attention [1.6 +/- 0.8]) were elevated
      in the overall sample. Psychological symptoms and quality-of-life concerns were
      generally similar across patients except for cardiac avoidance, which was
      significantly higher in newly diagnosed women after adjustments for disease
      severity (P = .05) and psychiatric history (P = .01). Peripartum cardiomyopathy
      specific quality-of-life concerns were also prevalent; however, group differences
      were nonsignificant (P = .07). CONCLUSIONS: Generalized anxiety, cardiac anxiety,
      and quality-of-life concerns are prevalent among patients with PPCM at all stages
      of recovery. Psychological issues may be an underrecognized aspect of women's
      recovery from PPCM.

PMID- 30273258
TI  - The Experiences of Younger Individuals Living With Heart Failure.
AB  - BACKGROUND: Heart failure (HF) impacts 1.7 million Americans between the ages of
      20 and 59 years, but limited research exists addressing the issues unique to this
      age group. OBJECTIVE: The aim of this study was to investigate the experiences of
      younger persons living with HF. METHODS: Semistructured interviews (n = 18) were
      analyzed using a qualitative thematic analysis. RESULTS: Six themes emerged: (1)
      role fulfillment: participants who perceived their roles as a parent, caregiver,
      spouse, employee, and friend have been negatively affected by HF; (2) autonomy:
      participants frequently linked their well-being to a sense of independence,
      productivity, and purpose; (3) financial impact: most of the sample expressed
      financial instability further complicated by existing disability policies; (4)
      perception of self: recurrent statements revealed participants feeling judged
      because of their HF diagnosis and younger age; (5) retrospective life changes:
      participants reflected on past decisions and often blamed themselves for their
      current health; and (6) symptom burden: participants reported higher levels of
      psychosocial symptoms, such as depression, anxiety, and fatigue. CONCLUSIONS:
      Younger individuals living with HF reported overwhelmingly poor health-related
      quality of life that was linked to the 6 themes identified previously. The effect
      of HF was seen on numerous life events that traditionally occur earlier in the
      life course such as establishing a career, meaningful relationships, family, and
      financial security. This directly impacted health-related quality of life by
      disrupting what each individual perceived as important to them, which took a toll
      on their overall mental health. To provide holistic care to younger patients
      living with HF, interventions that address the heavy burden of psychosocial
      symptoms and policy changes associated with financial burden and disability laws
      must be developed.

PMID- 30273259
TI  - The Relationship Among Health Beliefs, Depressive Symptoms, Medication Adherence,
      and Social Support in African Americans With Hypertension.
AB  - BACKGROUND: African Americans are disproportionately affected by hypertension and
      have lower medication adherence when compared to other racial groups. Antecedent
      factors such as beliefs surrounding hypertension, the presence or absence of
      social support, and depressive symptoms have not been extensively studied
      collectively in relation to hypertension medication adherence in African
      Americans. OBJECTIVE: To determine the associations among demographic and
      clinical factors, depressive symptoms, hypertension beliefs, and social support
      with blood pressure medication adherence in middle-aged African American adults
      with a diagnosis of hypertension. METHODS: A cross-sectional study of (N = 120)
      African Americans (mean age, 49 years; 22.5% men) with a current diagnosis of
      metabolic syndrome, including hypertension, who reported having and taking a
      prescribed blood pressure-lowering medication were included. Descriptive
      statistics, bivariate correlation analysis, and logistic regression using odds
      ratio were used to examine the effects of high blood pressure beliefs, social
      support, and depression on medication adherence. RESULTS: A small but significant
      relationship was found between medication adherence and number of comorbidities
      (r = 0.19, P = .04). In a multivariate regression model, after controlling for
      gender, comorbidities remained associated with medication adherence (beta = 0.
      77, P = .04). Depressive symptoms, high blood pressure beliefs, and social
      support did not have a significant relationship with medication adherence.
      CONCLUSIONS: Multiple comorbidities may have a positive impact upon medication
      adherence. Further study is needed in a larger sample of African Americans who
      have a diagnosis of hypertension in addition to other comorbidities requiring
      medication management.

PMID- 30273260
TI  - Experiences of Undergoing Enhanced External Counterpulsation in Patients With
      Refractory Angina Pectoris: A Qualitative Study.
AB  - BACKGROUND: Enhanced external counterpulsation (EECP) is a noninvasive treatment
      recommended for patients with refractory angina pectoris (RAP), which generally
      includes 35 one-hour sessions over 7 weeks. No study has described how patients
      experience the time before, during, and between sessions, as well as the time
      after EECP treatment. OBJECTIVE: The aim of this study was to describe how
      patients with RAP experience EECP treatment. METHODS: Semistructured interviews
      took place with 15 strategically selected patients (11 men, 58-91 years old) who
      had finished 7 weeks of EECP at the 2 existing EECP clinics in Sweden. Data were
      analyzed using inductive qualitative content analysis. RESULTS: The results were
      divided into 4 content areas, each comprising 3 categories: (1) experiences
      before EECP was initiated comprised uncharted territory, being given a new
      opportunity, and gain insight; (2) experiences during EECP sessions comprised
      physical discomfort, need of distraction, and sense of security; (3) experiences
      between EECP sessions comprised physical changes, socializing, and coordinating
      everyday life; and (4) experiences after 1 course of EECP treatment comprised
      improved physical well-being, improved mental well-being, and maintaining angina
      in check. CONCLUSIONS: Enhanced external counterpulsation was perceived as an
      unknown treatment option among these patients with RAP. Nurses should emphasize
      education before and during treatment based on individualized care needs to
      improve knowledge and treatment experience, as well as prevent discomfort. There
      is a great need to increase the awareness of EECP among healthcare professionals
      because it can improve the life situation for patients with RAP.

PMID- 30273262
TI  - Anti-DNase I Antibody: A New Serological Reactivity in Primary Sjogren Syndrome.
AB  - BACKGROUND AND OBJECTIVE: Primary Sjogren syndrome (pSS) is a systemic autoimmune
      rheumatic disease that particularly affects exocrine glands. Dry eye is one of
      the most important features of this syndrome, and a recent study reported reduced
      deoxyribonuclease I (DNase I) activity in the tear of patients with dry eye. We
      therefore postulated that patients with pSS might have antibodies targeting DNAse
      I. METHODS: We have evaluated in a cross-sectional study 85 patients with pSS
      (2002 American-European Consensus Group Criteria), 50 rheumatoid arthritis (RA)
      patients (1987 American College of Rheumatology Criteria) without sicca symptoms,
      and 88 healthy volunteers. IgG anti-DNase I was detected by enzyme-linked
      immunosorbent assay using as antigen bovine pancreas enzyme and confirmed by
      immunoblotting. RESULTS: Age and sex were alike in the 3 groups (p > 0.05). Anti
      DNase I was detected in 43.5% of the pSS patients. In contrast, this reactivity
      was absent in all RA patients (p = 0.0001). Additional comparison of pSS patients
      with (n = 37) or without (n = 48) anti-DNase I showed that the former group had
      higher IgG serum levels (2293.2 +/- 666.2 vs 1483.9 +/- 384.6 mg/dL, p = 0.0001)
      and greater rate of non-drug-induced leukopenia (43% vs 19%, p = 0.02). A
      multivariate logistic regression analysis identified that only IgG levels were
      independently associated with anti-DNase I. CONCLUSIONS: We describe a high
      frequency of anti-DNase I antibodies in pSS patients associated with higher serum
      IgG levels. The lack of this reactivity in RA patients without sicca symptoms
      suggests that this antibody may be helpful in the differential diagnosis of these
      diseases.

PMID- 30273263
TI  - Spinal Gout-Dual-Energy CT for Noninvasive Diagnosis.

PMID- 30273261
TI  - Comparison Between Non-High-Density Lipoprotein Cholesterol and Low-Density
      Lipoprotein Cholesterol to Estimate Cardiovascular Risk Using a Multivariate
      Model.
AB  - BACKGROUND: Although studies exist comparing low-density lipoprotein cholesterol
      (LDL-C) and non-high-density lipoprotein cholesterol (HDL-C) in the development
      of cardiovascular disease (CVD), most have limitations in the mathematical models
      used to evaluate their prognostic power adjusted for the other risk factors
      (cardiovascular risk). OBJECTIVE: The aim of this study was to compare LDL-C and
      non-HDL-C in patients with CVD to determine whether both parameters predict CVD
      similarly. METHODS: A cohort of 1322 subjects drawn from the general population
      of a Spanish region was followed between 1992 and 2006. The outcome was time to
      CVD. Secondary variables were gender, age, hypertension, diabetes, personal
      history of CVD, current smoker, body mass index, LDL-C, and non-HDL-C. Two CVD
      prediction models were constructed with the secondary variables, with only the
      lipid parameter varying (non-HDL-C or LDL-C). In the construction of the models,
      the following were considered: multiple imputation, events per variable of 10 or
      more, and continuous predictors as powers. The validation was conducted by
      bootstrapping obtaining the distribution of the C statistic (discrimination) and
      the probabilities observed by smooth curves. These results were compared in both
      models using graphical and analytical testing. RESULTS: There were a total of 137
      CVD events. The models showed no differences in the distributions of the C
      statistic (discrimination, P = .536) or in the calibration plot. CONCLUSIONS: In
      our population, LDL-C and non-HDL-C were equivalent at predicting CVD. More
      studies using this methodology are needed to confirm these results.

PMID- 30273264
TI  - Atypical Chronic Inflammatory ANCA-Positive Deforming Arthritis After Cocaine
      Levamisole Exposure.
AB  - BACKGROUND/OBJECTIVE: Immunostimulatory drugs including immune checkpoint
      inhibitors and levamisole can induce inflammatory disease including vasculitis,
      rashes, tissue necrosis, and arthritis. METHODS: This prospective cohort study
      determined the 5-year outcomes of cocaine-levamisole-induced inflammatory disease
      as to outcomes and survival. Thirty-one consecutive cocaine-levamisole autoimmune
      patients and 45 primary vasculitis patients were characterized as to clinical
      differentiating features, antineutrophil cytoplasmic antibody (ANCA) status,
      treatment, the presence of acute and chronic arthritis, and 5-year outcome.
      RESULTS: Seventy-one percent (22/31) of cocaine-levamisole vasculopathy cases
      were ANCA positive (86% p-ANCA and 14% c-ANCA), whereas 53% (23/45) of the
      primary vasculitis were ANCA positive (p = 0.04). The ANCA-positive cocaine
      levamisole cohort at onset were characterized by younger age (45 +/- 12 vs 53 +/-
      14 years, p = 0.04), superficial skin necrosis (82% vs 54%, p = 0.036), depressed
      complement C3 (27% vs 4%, p = 0.33), antiphospholipid antibodies (50% vs 4%, p <
      0.001), neutropenia (18% vs 0%, p = 0.044), and elevated antimyeloperoxidase
      (MPO) antibody levels (100% vs 67%, p < 0.001). Chronic cocaine-levamisole
      disease was characterized by severe cicatrical deformities of the face and
      extremities (45.5% vs 8.3%, p = 0.005). Arthralgias (71% vs 82%, p = 0.19) and
      acute arthritis (33% vs 32%, p = 0.25) were similar between the 2 groups.
      However, a substantial proportion cocaine-levamisole-induced autoimmune patients
      (18% vs 0%, p = 0.045) developed a chronic deforming inflammatory arthritis that
      was rheumatoid factor, anti-cyclic-citrillinated antibody antibody, and HLA-B27
      negative, but p-ANCA-and MPO antibody positive. CONCLUSIONS: Patients exposed to
      cocaine-levamisole may develop serious chronic sequelae including cicatrical
      cutaneous and facial deformities and an atypical seronegative, p-ANCA and MPO
      antibody-positive, HLA-B27-negative chronic deforming inflammatory arthritis.

PMID- 30273265
TI  - Report on the Second PANLAR Review Course in Rheumatology: Biosimilars Update.

PMID- 30273266
TI  - Pancreatitis, Panniculitis, and Polyarthritis.

PMID- 30273267
TI  - Sustainability of a Tuberculosis Screening Program at an Adult Education Center
      Through Community-Based Participatory Research.
AB  - The majority of active tuberculosis (TB) cases in the United States occur through
      reactivation of latent TB infection among foreign-born individuals. While
      screening of at-risk individuals through community partnerships is recommended,
      it is not commonly accomplished. A community-academic partnership developed a TB
      screening intervention at an adult education center serving a large foreign-born
      population in Rochester, Minnesota. The intervention was cocreated with grant
      support by diverse stakeholders through a community-based participatory research
      partnership. The intervention was sustained beyond the grant interval through
      adaptation of staffing inputs, a robust partnership with sustained dialogue
      around TB and operational issues, and adaptation of governance through
      coownership of the intervention by the adult education center and the public
      health department. Eight years of data demonstrate that adult education centers
      may be effective venues for sustaining partnerships to address TB prevention
      among at-risk communities.

PMID- 30273268
TI  - Quality Anesthesia: Medicine Measures, Patients Decide.
AB  - Quality has been defined by six domains: effective, equitable, timely, efficient,
      safe, and patient centered. Quality of anesthesia care can be improved through
      measurement, either through local measures in quality improvement or through
      national measures in value-based purchasing programs. Death directly related to
      anesthesia care has been reduced, but must be measured beyond simple mortality.
      To improve perioperative care for our patients, we must take shared
      accountability for all surgical outcomes including complications, which has
      traditionally been viewed as being surgically related. Anesthesiologists can also
      impact public health by being engaged in improving cognitive recovery after
      surgery and addressing the opiate crisis. Going forward, we must focus on what
      patients want and deserve: improved patient-oriented outcomes and satisfaction
      with our care. By listening to our patients and being engaged in the entire
      perioperative process, we can make the greatest impact on perioperative care.

PMID- 30273269
TI  - Hospital-, Anesthesiologist-, and Patient-level Variation in Primary Anesthesia
      Type for Hip Fracture Surgery: A Population-based Cross-sectional Analysis.
AB  - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS MANUSCRIPT TELLS US THAT IS NEW:
      BACKGROUND:: Substantial variation in primary anesthesia type for hip fracture
      surgery exists. Previous work has demonstrated that patients cared for at
      hospitals using less than 20 to 25% neuraxial anesthesia have decreased survival.
      Therefore, the authors aimed to identify sources of variation in anesthesia type,
      considering patient-, anesthesiologist-, and hospital-level variables. METHODS:
      Following protocol registration (NCT02787031), the authors conducted a cross
      sectional analysis of a population-based cohort using linked administrative data
      in Ontario, Canada. The authors identified all people greater than 65 yr of age
      who had emergency hip fracture surgery from April 2002 to March 2014. Generalized
      linear mixed models were used to account for hierarchal data and measure the
      adjusted association of hospital-, anesthesiologist-, and patient-level factors
      with neuraxial anesthesia use. The proportion of variation attributable to each
      level was estimated using variance partition coefficients and the median odds
      ratio for receipt of neuraxial anesthesia. RESULTS: Of 107,317 patients, 57,080
      (53.2%) had a neuraxial anesthetic. The median odds ratio for receiving neuraxial
      anesthesia was 2.36 between randomly selected hospitals and 2.36 between randomly
      selected anesthesiologists. The majority (60.1%) of variation in neuraxial
      anesthesia use was explained by patient factors; 19.9% was attributable to the
      anesthesiologist providing care and 20.0% to the hospital where surgery occurred.
      The strongest patient-level predictors were absence of preoperative anticoagulant
      or antiplatelet agents, absence of obesity, and presence of pulmonary disease.
      CONCLUSIONS: While patient factors explain most of the variation in neuraxial
      anesthesia use for hip fracture surgery, 40% of variation is attributable to
      anesthesiologist and hospital-level practice. Efforts to change practice patterns
      will need to consider hospital-level processes and anesthesiologists' intentions
      and behaviors.

PMID- 30273270
TI  - Self-efficacy as a Mechanism of Action of Imagery Rehearsal Therapy's
      Effectiveness: An Exploratory Mediation Analysis.
AB  - Imagery rehearsal therapy (IRT) is an empirically validated therapy targeting
      recurring nightmares, for which the mechanisms of action remain poorly
      understood. The objective of this study was to investigate how an exploratory
      measure of self-efficacy could mediate IRT's effectiveness. Thirty-five victims
      of sexual assault with recurring nightmares were randomly assigned to either IRT
      or a control condition. Participants completed questionnaires about self-efficacy
      and nocturnal symptoms at pre- and posttreatment. Regression analyses showed that
      IRT predicted greater self-efficacy about dreams (beta = .578) and that self
      efficacy about dreams predicted improvement in insomnia (beta = -.378). IRT also
      predicted greater self-efficacy about nightmares (beta = .366), which in turn
      predicts sleep quality (beta = -.412). However, self-efficacy was not a
      significant mediator of IRT's effectiveness on insomnia and sleep quality.
      Although IRT did increase patients' self-efficacy over dreams and nightmares,
      self-efficacy may not be a primary mechanism of action explaining IRT's
      effectiveness.

PMID- 30273272
TI  - Severity, Prevalence, Predictors, and Rate of Identification of Insomnia Symptoms
      in a Sample of Hospitalized Psychiatric Patients.
AB  - Insomnia is a risk factor for new onset, exacerbation, and relapse of mental
      illness. The goal of this study was to examine the prevalence, severity, and
      predictors of insomnia in hospitalized psychiatric patients. Ninety-seven
      consecutive psychiatric inpatients were administered the Insomnia Severity Index
      (ISI) to evaluate the presence and severity of insomnia. Patients' hospital
      charts were reviewed for demographic and medical information. ISI scores in 79.4%
      of the patients reached the threshold criterion of 8 for insomnia. Insomnia was
      not mentioned as a clinical problem in the discharge notes problem list in any of
      these patients. Multivariate analysis indicated that age (p = 0.009), recent
      suicide attempt or ideation (P < 0.001), tobacco use (p = 0.024), and
      recreational drug use during the past month (p = 0.040) were significant
      predictors of insomnia severity. Insomnia was highly prevalent in this
      population. Identification and management of insomnia would be an important
      clinical goal in hospitalized psychiatric patients.

PMID- 30273273
TI  - Suicide Methods According to Age and Sex: An Analysis of Data of 239,565 Suicide
      Victims in the Republic of Korea From 1991 to 2015.
AB  - Because suicide is irreversible, prevention is paramount. For the optimal
      strategy to reduce lethal means, we sought to investigate age- and sex-associated
      variations in suicide methods. Data on annual causes of death from 1991 to 2015
      in the Republic of Korea were used. Major sociodemographic correlates of the five
      suicide methods were analyzed by multiple multinominal logistic regression
      analysis. Among a total of 239,565 suicides from 1991 to 2015, hanging was most
      common. Gas poisoning sharply increased from 2007 to 2015. The gap between
      hanging and the second most common method of suicide has increased from 659 in
      2004 to 4,433 in 2015. Charcoal burning was most commonly used by males younger
      than 45 years of age, whereas pesticide was commonly used by both sexes ages 55
      years and older. Our results suggest that age- and sex-specific suicide
      prevention strategies are needed, particularly for gas and pesticide poisoning.

PMID- 30273271
TI  - Mental Health Impact of Homecoming Experience Among 1730 Formerly Deployed
      Veterans From the Vietnam War to Current Conflicts Results From the Veterans'
      Health Study.
AB  - We examined the effects of homecoming support on current mental health among 1730
      deployed veterans from Vietnam, Iraq/Afghanistan, Persian Gulf, and other
      conflicts. The prevalence of current posttraumatic stress disorder (PTSD) was
      5.4%, current depression was 8.3%, and 5.4% had suicidal thoughts in the past
      month. Overall, 26% of veterans had low homecoming support, which was more
      prevalent among Vietnam veterans (44.3%, p < 0.001). In multivariable logistic
      regressions, controlling for demographics, combat exposure, number of
      deployments, trauma history, and operational theater, low postdeployment support
      was associated with PTSD (odds ratio, 2.13; p = 0.032) and suicidality (odds
      ratio, 1.91; p < 0.030), but not depression. For suicidality, an interaction was
      detected for homecoming by theater status, whereby Iraq/Afghanistan veterans with
      lower homecoming support had a higher probability of suicidal thoughts (p =
      0.002). Thus, years after deployment, lower homecoming support was associated
      with current PTSD and suicidality, regardless of theater and warzone exposures.
      For suicidality, lower support had a greater impact on Iraq/Afghanistan veterans.

PMID- 30273274
TI  - Eating Pathology Among Patients With Anorexia Nervosa and Bulimia Nervosa: The
      Role of Narcissism and Self-Esteem.
AB  - We sought to deepen our understanding of the relationship between pathological
      narcissism and eating disorders (ED) by examining specific facets that composed
      grandiose and vulnerable narcissism while taking into account self-esteem, a well
      known and consistent risk factor for ED. Twenty-seven women diagnosed with
      anorexia nervosa (AN) and 23 women diagnosed with bulimia nervosa (BN) completed
      standardized measures of pathological narcissism, self-esteem, and dysfunctional
      eating attitudes and behaviors. Different patterns of associations between the
      facets of pathological narcissism and eating pathology arose between AN and BN
      diagnoses. Closer examination of the facets of pathological narcissism revealed
      that hiding the self, a vulnerable narcissistic facet, contributed significantly
      to dysfunctional eating attitudes and behaviors over and above self-esteem for
      women with AN. Hiding the self should continue to be explored in regard to
      treatment of ED.

PMID- 30273275
TI  - Is Tapping on Acupuncture Points an Active Ingredient in Emotional Freedom
      Techniques? A Systematic Review and Meta-analysis of Comparative Studies.
AB  - Emotional Freedom Techniques (EFTs) combine elements of cognitive restructuring
      and exposure techniques with acupoint stimulation. Meta-analyses indicate large
      effect sizes for posttraumatic stress disorder, depression, and anxiety; however,
      treatment effects may be due to components EFT shares with other therapies. This
      analysis reviewed whether EFTs acupressure component was an active ingredient.
      Six studies of adults with diagnosed or self-identified psychological or physical
      symptoms were compared (n = 403), and three (n = 102) were identified. Pretest
      vs. posttest EFT treatment showed a large effect size, Cohen's d = 1.28 (95%
      confidence interval [CI], 0.56 to 2.00) and Hedges' g = 1.25 (95% CI, 0.54 to
      1.96). Acupressure groups demonstrated moderately stronger outcomes than
      controls, with weighted posttreatment effect sizes of d = -0.47 (95% CI, -0.94 to
      0.0) and g = -0.45 (95% CI, -0.91 to 0.0). Meta-analysis indicated that the
      acupressure component was an active ingredient and outcomes were not due solely
      to placebo, nonspecific effects of any therapy, or nonacupressure components.

PMID- 30273276
TI  - Cognitive Impairment and Personality Traits in Epilepsy: Characterization and
      Risk Factor Analysis.
AB  - Cognitive impairment and personality disorders are severe comorbidities commonly
      observed in patients with epilepsy, and together they decrease the quality of
      patients' life. This study aimed to evaluate cognitive function and personality
      traits in patients with epilepsy with the Wechsler Adult Intelligence Scale
      Chinese revised and Eysenck Personality Questionnaire and investigate the
      underlying influencing factors. Compared with the control group, our results
      showed that patients with epilepsy were presented with significant cognitive
      impairment and particular personality traits. Epileptic seizure-related factors
      including earlier age of onset, longer duration of epileptic history, and higher
      seizure frequency were significantly associated with the observed defects in
      cognition and personality traits. In addition, the temporal lobe was more likely
      to affect cognition and personality, and the left hemisphere was closely related
      to verbal intelligence quotient, which needs to be the focus of future research.
      These results will be instrumental for guiding the treatment of epilepsy.

PMID- 30273278
TI  - Effects of Physical Exercise on Depressive Symptoms in Patients With Cognitive
      Impairment: A Systematic Review and Meta-Analysis.
AB  - We aimed to evaluate the efficacy of physical exercise in ameliorating depressive
      symptoms in patients with cognitive impairment. The databases of PubMed, EMBASE,
      Web of Science, the Cochrane Library, PsycINFO, China National Knowledge
      Infrastructure, WanFang, and WeiPu (VIP) were searched to identify randomized
      controlled trials (RCTs) that involved physical exercise for patients with
      cognitive impairment. A random effects model and a fixed effects model were used
      to calculate the pooled effect size. Twenty-one studies were identified. The meta
      analysis showed that physical exercise significantly ameliorated depressive
      symptoms (standardized mean difference [SMD] = -0.23; 95% confidence interval
      [CI], -0.39 to -0.07; p = 0.004). In addition, beneficial improvements in
      neuropsychiatric symptoms (mean difference, -4.62; 95% CI, -9.07 to -0.16, p =
      0.04), quality of life (SMD = 0.23; 95% CI, 0.01-0.46; p = 0.04), and activities
      of daily living (SMD = 0.27; 95% CI, 0.12-0.43; p = 0.0005) were observed in our
      study. No significant improvements were found in anxiety or apathy. Nevertheless,
      further high-quality, multicenter RCTs are needed to identify the clinical value
      of our results.

PMID- 30273279
TI  - Tattoo Recognition in Screening for Victims of Human Trafficking.
AB  - There is little information on the secondary prevention of human trafficking and
      how medical professionals can screen for victims. There is a paucity of validated
      screening tools for use in clinical settings to identify adult trafficked
      patients, although one for use in pediatric populations exists. Many victims
      withhold information about their trafficked status. Because traffickers may mark
      victims, identification of tattoos provides a useful method for screening
      patients, which complements history taking, especially when victims are unable to
      disclose that information. We searched existing medical literature, PsycINFO,
      PubMed, Google, and JSTOR using keywords "human," "trafficking," and "tattoos."
      Because there is scant literature on this topic, we also searched the gray
      literature that enabled preliminary identification of several themes used in
      trafficking tattoos. We also discussed tattoo placement and quality. Tattoo
      recognition is a critical factor in identifying victims and setting them on a
      pathway to freedom and recovery.

PMID- 30273277
TI  - A Positive Psychology Intervention to Promote Health Behaviors in Heart Failure:
      A Proof-of-Concept Trial.
AB  - : Patients with heart failure (HF) frequently struggle to adhere to health
      behaviors, and psychological factors may contribute to nonadherence. We examined
      the feasibility and acceptability of a 10-week, positive psychology (PP)-based
      intervention to promote health behavior adherence in patients (N = 10) with mild
      to moderate HF and suboptimal health behavior adherence. Participants engaged in
      weekly phone sessions, completed PP exercises (e.g., writing a gratitude letter,
      using a personal strength), and set goals related to diet, medication adherence,
      and physical activity. Feasibility was assessed by the number of sessions
      completed, and acceptability by participant ratings of ease and utility.
      Preliminary efficacy was measured by changes in psychological and adherence
      outcomes. The intervention was feasible (87% of exercises completed) and
      acceptable. Furthermore, in exploratory analyses, the intervention was associated
      with improvements in psychological and health behavior adherence outcomes.
      Larger, randomized trials are needed to further investigate the utility of this
      intervention. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02938052.

PMID- 30273280
TI  - The Critical Need for Pediatric and Juvenile Animal Research Addressing
      Gadolinium Retention in the Developing Body.

PMID- 30273281
TI  - Kinetic Analysis of Isometric Back Squats and Isometric Belt Squats.
AB  - Layer, JS, Grenz, C, Hinshaw, TJ, Smith, DT, Barrett, SF, and Dai, B. Kinetic
      analysis of isometric back squats and isometric belt squats. J Strength Cond Res
      32(12): 3301-3309, 2018-Belt squats seem to provide an alternative to back
      squats. However, it is not clear how musculoskeletal loading differs between the
      two. This study compared lower extremity and low-back kinetics during isometric
      back squats and isometric belt squats. Sixteen men (age: 22.6 +/- 3.4 years;
      height: 1.74 +/- 0.11 m; mass: 82.0 +/- 5.6 kg) and 10 women (age: 21.5 +/- 2.5
      years; height: 1.64 +/- 0.10 m; mass: 68.9 +/- 7.1 kg) performed isometric back
      squats and belt squats at 4 squat depths. Joint resultant moments were calculated
      from kinematic and ground reaction force data. Linear interpolation was used to
      estimate peak vertical forces and joint moments at a 45 degrees  thigh segment
      angle. Subjects increased peak forces, ankle moments, and knee moments but
      decreased low-back moments from back to belt squats (p <= 0.023). Hip moments did
      not significantly change between 2 squats. Subjects demonstrating smaller ankle
      and knee moments during back squats showed greater increases in these moments
      from back to belt squats (p <= 0.012, R <= 0.24). Subjects whose back squats were
      characterized by greater low-back moments displayed greater decreases in low-back
      moments from back to belt squats (p < 0.001, R = 0.98). Compared with isometric
      back squats, isometric belt squats may provide a similar or greater external
      loading for the musculoskeletal system of the lower extremities while reducing
      external spinal loading. Belt squats may be considered by individuals with upper
      body or spinal injuries and those displaying excessive external back moments.

PMID- 30273282
TI  - Cardiovascular Effects of Compression Garments During Uncompensable Heat Stress.
AB  - Bautz, J, Hostler, D, Khorana, P, and Suyama, J. Cardiovascular effects of
      compression garments during uncompensable heat stress. J Strength Cond Res XX(X):
      000-000, 2018-This study examined the potential hemodynamic benefits of wearing
      lower extremity compression garments (CGs) beneath thermal protective clothing
      (TPC) worn by wildland firefighters, while exercising in a heated environment.
      Using in a counterbalanced design, 10 male subjects ([mean +/- SD] age 27 +/- 6
      years, height 1.78 +/- 0.09 m, body mass 74.8 +/- 7.0 kg, body fat 10.6 +/- 4.2%,
      and V[Combining Dot Above]O2max 57.8 +/- 9.3 ml.kg.min) completed control (no CG)
      and experimental (CG) conditions in randomly assigned order. Protocols were
      separated by a minimum of 3 days. Subjects exercised for 90 minutes (three, 30
      minute segments) on a treadmill while wearing wilderness firefighter TPC and
      helmet in a heated room. Venous blood was drawn before and after exercise to
      measure hemoglobin (Hgb), hematocrit (Hct), serum osmolarity (OSM), and serum
      creatine phosphokinase (CPK). Vital signs and perceptual measures of exertion and
      thermal comfort were recorded during the protocol. Data were analyzed by the
      paired t-test. There were no differences in the change in heart rate (84 +/- 27
      vs. 85 +/- 14 b.min, p = 0.9), core temperature rise (1.8 +/- 0.6 vs. 1.9 +/- 0.5
      degrees  C, p = 0.39), or body mass lost (-1.72 +/- 0.78 vs. -1.77 +/- 0.58 kg, p
      = 0.7) between the conditions. There were no differences in the change in Hgb
      (0.49 +/- 0.66 vs. 0.33 +/- 1.11 g.dl, p = 0.7), Hct (1.22 +/- 1.92 vs. 1.11 +/-
      3.62%, p = 0.9), OSM (1.67 +/- 6.34 vs. 6.22 +/- 11.39 mOsm.kg, p = 0.3), or CPK
      (22.2 +/- 30.2 vs. 29.8 +/- 19.4 IU.L, p = 0.5). Total distance walked (3.9 +/-
      0.5 vs. 4.0 +/- 0.5 miles, p = 0.2), exercise interval (88.6 +/- 3.5 vs. 88.4 +/-
      3.6 minutes, p = 0.8), and perceptual measures were similar between conditions.
      Compression garments worn beneath TPC did not acutely alter the physiologic
      response to exertion in TPC. With greater use in the general public related to
      endurance activities, the data neither encourage nor discourage CG use during
      uncompensable heat stress.

PMID- 30273283
TI  - Power-Force-Velocity Profiling of Sprinting Athletes: Methodological and
      Practical Considerations When Using Timing Gates.
AB  - Haugen, TA, Breitschadel, F, and Samozino, P. Power-force-velocity profiling of
      sprinting athletes: Methodological and practical considerations when using timing
      gates. J Strength Cond Res XX(X): 000-000, 2018-The aim of this study was to
      investigate the impact of timing gate setup on mechanical outputs in sprinting
      athletes. Twenty-five male and female team sport athletes (mean +/- SD: 23 +/- 4
      years, 185 +/- 11 cm, 85 +/- 13 kg) performed two 40-m sprints with maximal
      effort. Dual-beamed timing gates covered the entire running course with 5-m
      intervals. Maximal horizontal force (F0), theoretical maximal velocity (v0),
      maximal horizontal power (Pmax), force-velocity slope (SFV), maximal ratio of
      force (RFmax), and index of force application technique (DRF) were computed using
      a validated biomechanical model and based on 12 varying split time combinations,
      ranging from 3 to 8 timing checkpoints. When no timing gates were located after
      the 20-m mark, F0 was overestimated (mean difference, +/-90% confidence level:
      0.16, +/-0.25 to 0.33, +/-0.28 N.kg; possibly to likely; small), in turn
      affecting SFV and DRF by small to moderate effects. Timing setups covering only
      the first 15 m displayed lower v0 than setups covering the first 30-40 m of the
      sprints (0.21, +/-0.34 to 0.25, +/-0.34 m.s; likely; small). Moreover, poorer
      reliability values were observed for timing setups covering the first 15-20 m vs.
      the first 25-40 m of the sprints. In conclusion, the present findings showed that
      the entire acceleration phase should be covered by timing gates to ensure
      acceptably valid and reliable sprint mechanical outputs. However, only 3 timing
      checkpoints (i.e., 10, 20, and 30 m) are required to ensure valid and reliable
      outputs for team sport athletes.

PMID- 30273284
TI  - Effects of Combined Plyometric and Short Sprint With Change-of-Direction Training
      on Athletic Performance of Male U15 Handball Players.
AB  - Hammami, M, Gaamouri, N, Aloui, G, Shephard, RJ, and Chelly, MS. Effects of
      combined plyometric and short sprint with change-of-direction training on
      athletic performance of male U15 handball players. J Strength Cond Res XX(X): 000
      000, 2018-This study examined the effects of combined plyometric and change-of
      direction training (CPT) on selected measures of performance (repeated-sprint T
      test [RSTT], sprint performance [5, 10, 20, and 30 m], change-of-direction tests
      [modified Illinois test and T-half test], squat jump, countermovement jump,
      countermovement jump with aimed arms 5-jump test, Y-balance test, Stork balance
      test, and 20-m shuttle run) in male U15 handball players. Players were randomly
      divided between experimental (n = 14; age: 14.5 +/- 0.3 years) and control (n =
      14; age: 14.6 +/- 0.2 years) groups. All trial participants trained and played
      matches together, but for 8 weeks in the latter part of the season, the
      experimental group replaced the tactical part of their normal regimen by a
      biweekly course of CPT. This induced significant increases in sprint times
      relative to controls (p = 0.006, effect size [ES] = 0.135, 8.7%; p=<0.001, ES =
      0.214, 7.4%; p = 0.022, ES = 0.096, 7.2%; and p = 0.032, ES = 0.085, 8.9% over
      distances of 5, 10, 20, and 30 m, respectively). The modified Illinois test and T
      half test also showed significant gains for experimental subjects (p < 0.025; ES
      = 0.205, 4.2% and p < 0.001; ES = 0.093, 5.3%, respectively), as did vertical and
      horizontal jumps. However, there were no significant changes of RSTT, 20-m
      shuttle run, or balance. Nevertheless, we conclude that the current CPT is
      effective in enhancing sprint performance, change-of-direction tests, and
      vertical and horizontal jumping and thus it can be commended to male U15 handball
      players as a useful option for improving important components of their physical
      performance.

PMID- 30273285
TI  - Sex Differences and Patterns of Muscle Stiffness in the Knee Flexor and Extensor
      Musculature Through Analysis of Isolated Bellies.
AB  - Martin-San Agustin, R, Benitez-Martinez, JC, Medina-Mirapeix, F, and Casana
      Granell, J. Sex differences and patterns of muscle stiffness in the knee flexor
      and extensor musculature through analysis of isolated bellies. J Strength Cond
      Res XX(X): 000-000, 2018-Muscle stiffness (MS) is one of the key factors in joint
      control. The purpose of this study was to determine sex differences in the MS of
      5 isolated muscle bellies (biceps femoris [BF], semitendinosus [ST], rectus
      femoris [RF], vastus medialis [VM], and vastus lateralis [VL]) and in the pattern
      of differences among their respective MS. Twenty female and 20 male recreational
      athletes participated. Muscle stiffness was measured by tensiomyography using
      maximum radial deformation (Dm) as an indirect indicator of MS. Sex differences
      were observed only in the Dm of RF (mean difference = 2.07 mm, p < 0.05) when
      values were adjusted by body mass and stature. Males and females showed a similar
      pattern in the Dm between the muscle bellies: within the hamstrings, ST had a
      significantly higher Dm than BF in females (3.02 mm) and males (4.28 mm); within
      the quadriceps, RF also had a significantly higher value than VL and VM in
      females (6.50 and 7.38 mm, respectively) and males (4.87 and 4.82 mm,
      respectively). Sex differences in patterns were found between BF and the vastus
      muscles: the BF of females had a significantly higher Dm than VL (3.78 mm) and VM
      (4.51 mm), but this was not observed in males. Differences may imply different
      involvement of the bellies in countering the movements of the lower extremities.
      Our results can help to direct exercises to improve the MS in certain muscular
      bellies.

PMID- 30273286
TI  - Muscular Fitness and Cardiovascular Risk Factors in Children and Adolescents: A
      Systematic Review.
AB  - Rodrigues de Lima, T, Custodio Martins, P, Henrique Guerra, P, and Augusto Santos
      Silva, D. Muscular fitness and cardiovascular risk factors in children and
      adolescents: A systematic review. J Strength Cond Res XX(X): 000-000, 2018-The
      purpose of this study was to identify and summarize the relationships between
      muscular fitness (MF) and individual components of metabolic syndrome (high waist
      circumference [WC], high blood pressure [BP], high systolic BP [SBP], high
      diastolic BP [DBP], high triglycerides [TG], fasting blood glucose [FG], and low
      HDL cholesterol levels [HDL-C]) in children and adolescents. A systematic review
      was conducted in 5 electronic databases, with complementary searches in reference
      lists, and the inclusion criteria were children and adolescents (age group up to
      19 years of age) with no special clinical conditions. In all articles, risk of
      bias was analyzed by a standardized instrument. Of the 5,973 articles initially
      identified, 21 were included, with data on 22,261 children and adolescents.
      Higher MF values were associated with lower TG (n = 07) and WC values (n = 15).
      Different results in relation to the relationship between MF and SBP (n = 10) and
      MF and DBP (n = 07) were verified. In addition, there was no relationship between
      MF and FG (n = 06). In addition, inconclusive results were verified in the
      relationship between MF and HDL-C (n = 07). Concluded higher MF values were
      related to lower WC values and lower TG concentrations.

PMID- 30273287
TI  - Injury Prevention Programs Based on Flywheel vs. Body Weight Resistance in
      Recreational Athletes.
AB  - Monajati, A, Larumbe-Zabala, E, Sampson, MG, and Naclerio, F. Injury prevention
      programs based on flywheel vs. body weight resistance in recreational athletes. J
      Strength Cond Res XX(X): 000-000, 2018-This study compares the effect of an
      isoinertial flywheel technology vs. a traditional gravity-dependent exercise
      protocol on modifiable factors associated with the incidence of hamstring strain
      (HAM) and anterior cruciate ligament (ACL) injuries. Furthermore, the effect on
      repeated sprint ability was also considered. Eighteen recreationally trained
      volleyball players completed one of the following 6-week protocols: (a) flywheel
      (FY) included 3 exercises using a YoYo isoinertial-squat machine and 3 exercises
      with a Versa-Pulley isoinertial device, and (b) gravity-dependent (GT) involved 6
      similar exercises with no external resistance (participants' body weight). Both
      programs consisted in 2 sessions.wk performing 2 sets of 8 repetitions with 2
      minutes of rest. Outcomes included a 10-second tuck jump assessment (TJA),
      landing knee valgus score, hamstring and quadriceps concentric and eccentric
      isokinetic 60 degrees .s peak torque, optimal peak torque localization,
      conventional and functional hamstring-to-quadriceps ratio, and 10-m repeated
      shuttle sprint ability (RSSA) test. FY improved TJA (-2, interquartile range
      [IQR] = -3 to -1) and valgus (-1, IQR = -1 to 0) scores, hamstring eccentric
      (20.37, 95% confidence interval [CI] = 9.27-31.47 N.m) and concentric (17.87, 95%
      CI = 0.40-35.34 N.m) peak torque, as well as the RSSA (-0.28, 95% CI = -0.45 to 
      0.10 seconds), whereas GT only improved hamstring eccentric peak torque (21.41,
      95% CI = 9.00-33.82 N.m). A 6-week protocol using flywheel technology seems to
      elicit better positive adaptations to protect athletes from HAM and ACL injuries
      and to enhance RSSA performance compared to exercising with no external
      resistance other than athletes' body weight.

PMID- 30273288
TI  - Resistance Training Improves a Cellular Health Parameter in Obese Older Women: A
      Randomized Controlled Trial.
AB  - Ribeiro, AS, Schoenfeld, BJ, dos Santos, L, Nunes, JP, Tomeleri, CM, Cunha, PM,
      Sardinha, LB, and Cyrino, ES. Resistance training improves a cellular health
      parameter in obese older women: a randomized controlled trial. J Strength Cond
      Res XX(X): 000-000, 2018-Phase angle (PhA) is a viable indicator of cellular
      health, with higher values reflecting better cellularity, cell membrane
      integrity, and cell function. Adaptive responses to resistance training (RT) on
      PhA may be important in obese older people. The main purpose of the present study
      was to investigate the effects of 8 weeks of RT on PhA in obese older women.
      Thirty-three obese older women (68.1 +/- 5.7 years, 71.6 +/- 10.1 kg, 154.5 +/-
      6.7 cm, 30.0 +/- 4.1 kg.m, and 45.0 +/- 6.0% body fat) were randomly allocated
      into 1 of 2 groups: a training group that performed the RT program (TG, n = 18)
      or a nonexercise control group (CG, n = 15). The whole-body RT consisted of an 8
      week RT program involving 8 exercises performed for 3 sets of 8-12 repetitions 3
      times a week. Anthropometric, body fat and fat-free mass, PhA, total body water
      (TBW), intracellular water (ICW), and extracellular water compartments were
      performed at before and after training. After the intervention period, the TG
      presented greater increases (p < 0.05) than CG for fat-free mass (TG = +1.3% and
      CG = -0.3%), TBW (TG = +2.0% and CG = -1.7%), ICW (TG = +3.1% and CG = -1.9%),
      and PhA (TG = +3.4% and CG = -1.4%), and lower values for percentage of body fat
      (TG = -1.3% and CG = +0.9%) and bioimpedance resistance (TG = -4.6% and CG =
      +2.3%). Our results suggest that 8 weeks of RT improves PhA-a cellular health
      parameter-in obese older women.

PMID- 30273289
TI  - Fit to Teach?-Cardiorespiratory Capacity, Vitamin D3, and Ferritin in Physical
      Education Teachers With Specialization in Dance.
AB  - Schmidt, M, Ohlendorf, D, Groneberg, DA, and Wanke, EM. Fit to teach?
      Cardiorespiratory capacity, vitamin D3, and ferritin in physical education
      teachers with specialization in dance. J Strength Cond Res XX(X): 000-000, 2018
      Numerous studies have shown that good cardiorespiratory capacity is of great
      importance for a healthy and long-term professional career as a dancer. Although
      the cardiorespiratory demands during teaching can reach into the submaximal
      intensity range, current data on the objective physical fitness of this
      occupational group are still missing. The aim of this pilot project was to
      determine selected cardiorespiratory parameters. In addition, measurements of the
      vitamin D3 (25(OH)D3) and iron balance as well as a subjective assessment of
      dance teachers' (DTs) fitness were performed. Twenty-one DTs (f: n = 18, m: n =
      3) aged 48.2 +/- 9.3 years were examined for cardiorespiratory performance within
      the framework of maximum bicycle spiroergometry. In addition, the self-perception
      of DTs' fitness was examined as well as the serum vit D3 levels and ferritin
      concentration in the blood. The cardiorespiratory fitness of DTs can be assessed
      as average (maximal oxygen consumption, V[Combining Dot Above]O2max = 29.5 +/-
      7.1 ml.k.min; physical working capacity, PWCmax = 165.0 +/- 44.4). The DTs seemed
      to underestimate or overestimate their own capacity. Laboratory diagnostics
      showed that the 25(OH)D3 levels (21.8 +/- 8.5 ng.ml) and serum ferritin values
      (102.4 +/- 35.0 g.dl) were not optimal for almost the entire sample. In view of
      the physical occupational requirements, an increase in aerobic cardiorespiratory
      fitness by endurance-oriented basic training for DTs seems advisable. In
      addition, the substitution of vit D3 is worth being discussed.

PMID- 30273290
TI  - Effects of Lower-Body Muscular Fatigue on Vertical Jump and Balance Performance.
AB  - Cooper, CN, Dabbs, NC, Davis, J, and Sauls, NM. Effects of lower-body muscular
      fatigue on vertical jump and balance performance. J Strength Cond Res XX(X): 000
      000, 2018-Lower-body fatigue can lead to a decline in vertical jump (VJ) and
      balance performance due to decreased motor control and coordination. The purpose
      is to determine the effects of lower-body fatigue on VJ and balance performance.
      Twenty-four recreationally trained individuals participated in a single 1-hour
      familiarization and testing session. Participants were familiarized with balance,
      countermovement vertical jump (CMVJ), and static vertical jump (SVJ) using the
      Vertec. Three trials of static and dynamic balance tests were completed. Three
      trials of a SVJ and CMVJ were completed in a randomized order pre/post fatigue
      protocol. Three trials of double-leg and single-leg tests were performed.
      Dependent t tests analyzed differences between pre/post fatigue protocol for
      jumping and balance measures. There was a significant (p < 0.001) difference
      between pre/post measures for SVJ-H (height), CMVJ-H, and CMVJ peak power (PP).
      Results showed an interaction (p < 0.05) for group by time for CMVJ-H, CMVJ-peak
      force (PF), SVJ-PF, and SVJ-PP. There were no main effects (p > 0.05) for time or
      group for SVJ-rate of velocity development and SVJ-impact force (IF). There were
      no interactions, time effects, and group effects for balance variables (p >
      0.05). Bosco protocol decreased VJ height and PF in SVJ, and VJ height and PF,
      IF, peak velocity, and PP for CMVJ potentially due to decreased muscle control,
      coordination, and force-generating capacity after fatigue. Practitioners should
      consider fatiguing effects on individuals performing jumping motions but it seems
      that fatigue has no effect on balance.

PMID- 30273291
TI  - Acute Hormonal Response to Kettlebell Swing Exercise Differs Depending on Load,
      Even When Total Work Is Normalized.
AB  - Raymond, LM, Renshaw, D, and Duncan, MJ. Acute hormonal response to kettlebell
      swing exercise differs depending on load, even when total work is normalized. J
      Strength Cond Res XX(X): 000-000, 2018-This study examined the acute hormonal
      response to kettlebell (KB) swing exercise using 2 loads, but when total work was
      equalized. Ten strength-trained males (25 +/- 6 years) completed 2 KB swing
      trials, with an 8- and 16-kg KB, respectively, in a counterbalanced order. Each
      protocol lasted 12 minutes comprising 30-second KB swings followed by 30-second
      rest. Swing cadence was manipulated in each trial to ensure that total weight
      lifted was the same across conditions. Heart rate (HR) and ratings of perceived
      exertion (RPE), using the Borg RPE scale 6-20, were taken at the end of each 30
      second exercise period. Saliva samples (min 0.5 ml) were taken 15 minutes before,
      immediately after, and 15 and 30 minutes after each condition from which cortisol
      (C) and testosterone (T) were determined. Results indicated a significant main
      effect for load for C (p = 0.007) and T (p = 0.05) where higher values for both C
      and T were evident for the 16-kg load. There was also a significant main effect
      for time for T (p = 0.001), where T values were all significantly higher post
      exercise compared with pre-exercise. For HR, there were significant main effects
      for load (p = 0.004) and time (p = 0.001) with higher HR seen in 16-kg load and
      significant increases in HR evident with increasing repetition, irrespective of
      condition (all p < 0.05). Rating of perceived exertion values increased with
      repetition for the 8-kg and 16-kg loads, but the increase was more marked for the
      16-kg load compared with the 8-kg load (p = 0.002). The present findings suggest
      that KB swing exercise produces an acute increase in hormones involved in muscle
      adaptation, but that KB load influences this response, even when total work
      completed is the same.

PMID- 30273292
TI  - Relationship Between Maximal Dynamic Force in the Deep Back Squat and Sprinting
      Performance in Consecutive Segments Up to 30 m.
AB  - Mock, S, Hartmann, R, Wirth, K, Rosenkranz, G, and Mickel, C. Relationship
      between maximal dynamic force in the deep back squat and sprinting performance in
      consecutive segments up to 30 m. J Strength Cond Res XX(X): 000-000, 2018-The
      sprint (in track and field athletics) is characterized by a fluent transition
      from predominantly knee extending musculature during the initial acceleration
      phase toward dominance of the hamstring muscle group thereafter. Because of this
      change in technique, it can be assumed that there is a decrease of correlation of
      the maximal dynamic force of the deep back squat and sprinting performance with
      increasing distance. Therefore, sprinting performance for consecutive intervals
      (0-5, 5-10, 10-15, 15-20, 20-25, and 25-30 m) as well as the 1 repetition maximum
      (1RM) were determined. Our results show statistically significant (p < 0.01)
      correlations for both the relationships with the absolute 1RM (r = -0.614 to 
      0.808) and the relative 1RM (r = -0.646 to -0.749). However, the expected
      decrease in correlation over distance was not found. The results show that the
      maximal dynamic force of hip and knee extensors are a basic performance
      requirement in short-distance sprinting and should be considered in training
      recommendations.

PMID- 30273293
TI  - Infectious Disease Threats and Opportunities for Prevention.

PMID- 30273294
TI  - The Information Imperative for Public Health: A Call to Action to Become
      Informatics-Savvy.

PMID- 30273295
TI  - Starting Out Right: What Are the Essential Elements of New State and Territorial
      Health Official Onboarding and Transition?

PMID- 30273297
TI  - Practical Solutions for a Healthier Workforce.

PMID- 30273296
TI  - Local Health Department Response to Opioid Use and Abuse: Findings From the 2018
      Forces of Change Survey.

PMID- 30273299
TI  - Coming Down from Opioids.

PMID- 30273300
TI  - Break Down Silos.

PMID- 30273298
TI  - Mahanimbine Exerts Anticancer Effects on Human Pancreatic Cancer Cells by
      Triggering Cell Cycle Arrest, Apoptosis, and Modulation of AKT/Mammalian Target
      of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription 3
      (STAT3) Signalling Pathways.
AB  - BACKGROUND Pancreatic cancer causes tremendous mortality across the globe mainly
      due to late diagnosis and unavailability of efficient chemotheruptic agents. In
      the current study the anticancer potential of a plant derived alkaloid,
      Mahanimbine, was examined against a panel of pancreatic cancer cells. MATERIAL
      AND METHODS The cell proliferation was determined by MTT assay. Annexin V/PI and
      DAPI staining were performed to detect apoptosis. Cell cycle distribution was
      investigated by flow cytometery. Cell migration was detected by wound healing
      assay and protein expression was checked by western blotting. RESULTS The results
      revealed that Mahanimbine could inhibit the proliferation of the all the
      pancreatic cancer cells with lower cytoxicity against the normal cells. The IC50
      ranged from 3.5 to 64 uM against the pancreatic cancer cell lines. The lowest
      IC50 of 3.5 uM was observed tor the Capan-2 and SW119 pancreatic cancer cell
      lines. The anticancer activity of Mahanimbine against the Capan-2 and SW119 cells
      was found to be due to G0/G1 cell cycle arrest and induction of apoptosis.
      Mahanimbine prompted apoptosis was also associated with decline in Bcl-2 and
      enhancement of the Bax expression. Further, it was observed that Mahanimbine
      could inhibit the AKT/mTOR and STAT3 signalling pathways in the Capan-2 and SW119
      pancreatic cancer cells. The effects of the Mahanimbine were also examined on the
      migration of the Capan-2 and SW119 pancreatic cancer cells. It was found that
      Mahanimbine could inhibit the motility and migration of both the pancreatic
      cancer cell lines. CONCLUSIONS We found that Mahanimbine inhibits the
      proliferation of pancreatic cancer cells and as such Mahanimbine may prove
      beneficial in the management of pancreatic cancer.

PMID- 30273301
TI  - New Drugs from Old.

PMID- 30273302
TI  - Missing E.T.

PMID- 30273303
TI  - Rethink Funding.

PMID- 30273304
TI  - Help Young Scientists.

PMID- 30273307
TI  - Honey, I Shrunk the Mammals.

PMID- 30273306
TI  - Seeing Blind.

PMID- 30273305
TI  - Rabies on the Brain.

PMID- 30273309
TI  - A Conversation with the Only Physicist in Congress.

PMID- 30273308
TI  - The Un(solv)able Problem.

PMID- 30273310
TI  - Brain Bar Codes.

PMID- 30273312
TI  - Quick Hits.

PMID- 30273311
TI  - Recommended.

PMID- 30273313
TI  - Make Research Reproducible.

PMID- 30273314
TI  - Postpartum Relief.

PMID- 30273315
TI  - True Story.

PMID- 30273316
TI  - How to Fix Science.

PMID- 30273317
TI  - Druggists Shouldn't Be Morality Police.

PMID- 30273318
TI  - Slippery Slope.

PMID- 30273320
TI  - Letters.

PMID- 30273319
TI  - This Way Out.

PMID- 30273321
TI  - Earthquakes in the Sky.

PMID- 30273322
TI  - Tinder for Cheetahs.

PMID- 30273323
TI  - 5G Is Just around the Corner.

PMID- 30273324
TI  - Body Balance.

PMID- 30273325
TI  - Flock Immunity.

PMID- 30273326
TI  - A Mysterious Change of Mind.

PMID- 30273327
TI  - Heading Off Injury.

PMID- 30273329
TI  - 50, 100 &150 Years Ago.

PMID- 30273328
TI  - Clicks, Lies and Videotape.

PMID- 30273330
TI  - Proof of the Impossible?

PMID- 30273331
TI  - End Harassment.

PMID- 30273332
TI  - Use of an individual-based model of pneumococcal carriage for planning a
      randomized trial of a whole-cell vaccine.
AB  - For encapsulated bacteria such as Streptococcus pneumoniae, asymptomatic carriage
      is more common and longer in duration than disease, and hence is often a more
      convenient endpoint for clinical trials of vaccines against these bacteria.
      However, using a carriage endpoint entails specific challenges. Carriage is
      almost always measured as prevalence, whereas the vaccine may act by reducing
      incidence or duration. Thus, to determine sample size requirements, its impact on
      prevalence must first be estimated. The relationship between incidence and
      prevalence (or duration and prevalence) is convex, saturating at 100% prevalence.
      For this reason, the proportional effect of a vaccine on prevalence is typically
      less than its proportional effect on incidence or duration. This relationship is
      further complicated in the presence of multiple pathogen strains. In addition,
      host immunity to carriage accumulates rapidly with frequent exposures in early
      years of life, creating potentially complex interactions with the vaccine's
      effect. We conducted a simulation study to predict the impact of an inactivated
      whole cell pneumococcal vaccine-believed to reduce carriage duration-on carriage
      prevalence in different age groups and trial settings. We used an individual
      based model of pneumococcal carriage that incorporates relevant immunological
      processes, both vaccine-induced and naturally acquired. Our simulations showed
      that for a wide range of vaccine efficacies, sampling time and age at vaccination
      are important determinants of sample size. There is a window of favorable
      sampling times during which the required sample size is relatively low, and this
      window is prolonged with a younger age at vaccination, and in a trial setting
      with lower transmission intensity. These results illustrate the ability of
      simulation studies to inform the planning of vaccine trials with carriage
      endpoints, and the methods we present here can be applied to trials evaluating
      other pneumococcal vaccine candidates or comparing alternative dosing schedules
      for the existing conjugate vaccines.

PMID- 30273334
TI  - Use of structural equation models to predict dengue illness phenotype.
AB  - BACKGROUND: Early recognition of dengue, particularly patients at risk for plasma
      leakage, is important to clinical management. The objective of this study was to
      build predictive models for dengue, dengue hemorrhagic fever (DHF), and dengue
      shock syndrome (DSS) using structural equation modelling (SEM), a statistical
      method that evaluates mechanistic pathways. METHODS/FINDINGS: We performed SEM
      using data from 257 Thai children enrolled within 72 h of febrile illness onset,
      156 with dengue and 101 with non-dengue febrile illnesses. Models for dengue,
      DHF, and DSS were developed based on data obtained three and one day(s) prior to
      fever resolution (fever days -3 and -1, respectively). Models were validated
      using data from 897 subjects who were not used for model development. Predictors
      for dengue and DSS included age, tourniquet test, aspartate aminotransferase, and
      white blood cell, % lymphocytes, and platelet counts. Predictors for DHF included
      age, aspartate aminotransferase, hematocrit, tourniquet test, and white blood
      cell and platelet counts. The models showed good predictive performances in the
      validation set, with area under the receiver operating characteristic curves
      (AUC) at fever day -3 of 0.84, 0.67, and 0.70 for prediction of dengue, DHF, and
      DSS, respectively. Predictive performance was comparable using data based on the
      timing relative to enrollment or illness onset, and improved closer to the
      critical phase (AUC 0.73 to 0.94, 0.61 to 0.93, and 0.70 to 0.96 for dengue, DHF,
      and DSS, respectively). CONCLUSIONS: Predictive models developed using SEM have
      potential use in guiding clinical management of suspected dengue prior to the
      critical phase of illness.

PMID- 30273333
TI  - A survey of inter-individual variation in DNA methylation identifies
      environmentally responsive co-regulated networks of epigenetic variation in the
      human genome.
AB  - While population studies have resulted in detailed maps of genetic variation in
      humans, to date there are few robust maps of epigenetic variation. We identified
      sites containing clusters of CpGs with high inter-individual epigenetic
      variation, termed Variably Methylated Regions (VMRs) in five purified cell types.
      We observed that VMRs occur preferentially at enhancers and 3' UTRs. While the
      majority of VMRs have high heritability, a subset of VMRs within the genome show
      highly correlated variation in trans, forming co-regulated networks that have low
      heritability, differ between cell types and are enriched for specific
      transcription factor binding sites and biological pathways of functional
      relevance to each tissue. For example, in T cells we defined a network of 95 co
      regulated VMRs enriched for genes with roles in T-cell activation; in fibroblasts
      a network of 34 co-regulated VMRs comprising all four HOX gene clusters enriched
      for control of tissue growth; and in neurons a network of 18 VMRs enriched for
      roles in synaptic signaling. By culturing genetically-identical fibroblasts under
      varying environmental conditions, we experimentally demonstrated that some VMR
      networks are responsive to the environment, with methylation levels at these loci
      changing in a coordinated fashion in trans dependent on cellular growth.
      Intriguingly these environmentally-responsive VMRs showed a strong enrichment for
      imprinted loci (p<10-80), suggesting that these are particularly sensitive to
      environmental conditions. Our study provides a detailed map of common epigenetic
      variation in the human genome, showing that both genetic and environmental causes
      underlie this variation.

PMID- 30273335
TI  - Amn1 governs post-mitotic cell separation in Saccharomyces cerevisiae.
AB  - Post-mitotic cell separation is one of the most prominent events in the life
      cycle of eukaryotic cells, but the molecular underpinning of this fundamental
      biological process is far from being concluded and fully characterized. We use
      budding yeast Saccharomyces cerevisiae as a model and demonstrate AMN1 as a major
      gene underlying post-mitotic cell separation in a natural yeast strain, YL1C.
      Specifically, we define a novel 11-residue domain by which Amn1 binds to Ace2.
      Moreover, we demonstrate that Amn1 induces proteolysis of Ace2 through the
      ubiquitin proteasome system and in turn, down-regulates Ace2's downstream target
      genes involved in hydrolysis of the primary septum, thus leading to inhibition of
      cell separation and clumping of haploid yeast cells. Using ChIP assays and site
      specific mutation experiments, we show that Ste12 and the a1-alpha12 heterodimer
      are two direct regulators of AMN1. Specifically, a1-alpha2, a diploid-specific
      heterodimer, prevents Ste12 from inactivating AMN1 through binding to its
      promoter. This demonstrates how the Amn1-governed cell separation is highly cell
      type dependent. Finally, we show that AMN1368D from YL1C is a dominant allele in
      most strains of S. cerevisiae and evolutionarily conserved in both genic
      structure and phenotypic effect in two closely related yeast species, K. lactis
      and C. glabrata.

PMID- 30273336
TI  - Exploring the impact of inoculum dose on host immunity and morbidity to inform
      model-based vaccine design.
AB  - Vaccination is an effective method to protect against infectious diseases. An
      important consideration in any vaccine formulation is the inoculum dose, i.e.,
      amount of antigen or live attenuated pathogen that is used. Higher levels
      generally lead to better stimulation of the immune response but might cause more
      severe side effects and allow for less population coverage in the presence of
      vaccine shortages. Determining the optimal amount of inoculum dose is an
      important component of rational vaccine design. A combination of mathematical
      models with experimental data can help determine the impact of the inoculum dose.
      We illustrate the concept of using data and models to inform inoculum dose
      determination for vaccines, wby fitting a mathematical model to data from
      influenza A virus (IAV) infection of mice and human parainfluenza virus (HPIV)
      infection of cotton rats at different inoculum doses. We use the model to map
      inoculum dose to the level of immune protection and morbidity and to explore how
      such a framework might be used to determine an optimal inoculum dose. We show how
      a framework that combines mathematical models with experimental data can be used
      to study the impact of inoculum dose on important outcomes such as immune
      protection and morbidity. Our findings illustrate that the impact of inoculum
      dose on immune protection and morbidity can depend on the specific pathogen and
      that both protection and morbidity do not necessarily increase monotonically with
      increasing inoculum dose. Once vaccine design goals are specified with required
      levels of protection and acceptable levels of morbidity, our proposed framework
      can help in the rational design of vaccines and determination of the optimal
      amount of inoculum.

PMID- 30273337
TI  - Linking signal detection theory and encoding models to reveal independent neural
      representations from neuroimaging data.
AB  - Many research questions in visual perception involve determining whether stimulus
      properties are represented and processed independently. In visual neuroscience,
      there is great interest in determining whether important object dimensions are
      represented independently in the brain. For example, theories of face recognition
      have proposed either completely or partially independent processing of identity
      and emotional expression. Unfortunately, most previous research has only vaguely
      defined what is meant by "independence," which hinders its precise quantification
      and testing. This article develops a new quantitative framework that links signal
      detection theory from psychophysics and encoding models from computational
      neuroscience, focusing on a special form of independence defined in the
      psychophysics literature: perceptual separability. The new theory allowed us, for
      the first time, to precisely define separability of neural representations and to
      theoretically link behavioral and brain measures of separability. The framework
      formally specifies the relation between these different levels of perceptual and
      brain representation, providing the tools for a truly integrative research
      approach. In particular, the theory identifies exactly what valid inferences can
      be made about independent encoding of stimulus dimensions from the results of
      multivariate analyses of neuroimaging data and psychophysical studies. In
      addition, commonly used operational tests of independence are re-interpreted
      within this new theoretical framework, providing insights on their correct use
      and interpretation. Finally, we apply this new framework to the study of
      separability of brain representations of face identity and emotional expression
      (neutral/sad) in a human fMRI study with male and female participants.

PMID- 30273338
TI  - High-risk human papillomavirus status and prognosis in invasive cervical cancer:
      A nationwide cohort study.
AB  - BACKGROUND: High-risk human papillomavirus (hrHPV) infection is established as
      the major cause of invasive cervical cancer (ICC). However, whether hrHPV status
      in the tumor is associated with subsequent prognosis of ICC is controversial. We
      aim to evaluate the association between tumor hrHPV status and ICC prognosis
      using national registers and comprehensive human papillomavirus (HPV) genotyping.
      METHODS AND FINDINGS: In this nationwide population-based cohort study, we
      identified all ICC diagnosed in Sweden during the years 2002-2011 (4,254
      confirmed cases), requested all archival formalin-fixed paraffin-embedded blocks,
      and performed HPV genotyping. Twenty out of 25 pathology biobanks agreed to the
      study, yielding a total of 2,845 confirmed cases with valid HPV results. Cases
      were prospectively followed up from date of cancer diagnosis to 31 December 2015,
      migration from Sweden, or death, whichever occurred first. The main exposure was
      tumor hrHPV status classified as hrHPV-positive and hrHPV-negative. The primary
      outcome was all-cause mortality by 31 December 2015. Five-year relative survival
      ratios (RSRs) were calculated, and excess hazard ratios (EHRs) with 95%
      confidence intervals (CIs) were estimated using Poisson regression, adjusting for
      education, time since cancer diagnosis, and clinical factors including age at
      cancer diagnosis and International Federation of Gynecology and Obstetrics (FIGO)
      stage. Of the 2,845 included cases, hrHPV was detected in 2,293 (80.6%), and we
      observed 1,131 (39.8%) deaths during an average of 6.2 years follow-up. The
      majority of ICC cases were diagnosed at age 30-59 years (57.5%) and classified as
      stage IB (40.7%). hrHPV positivity was significantly associated with screen
      detected tumors, young age, high education level, and early stage at diagnosis (p
      < 0.001). The 5-year RSR compared to the general female population was 0.74 (95%
      CI 0.72-0.76) for hrHPV-positive cases and 0.54 (95% CI 0.50-0.59) for hrHPV
      negative cases, yielding a crude EHR of 0.45 (95% CI 0.38-0.52) and an adjusted
      EHR of 0.61 (95% CI 0.52-0.71). Risk of all-cause mortality as measured by EHR
      was consistently and statistically significantly lower for cases with hrHPV
      positive tumors for each age group above 29 years and each FIGO stage above IA.
      The difference in prognosis by hrHPV status was highly robust, regardless of the
      clinical, histological, and educational characteristics of the cases. The main
      limitation was that, except for education, we were not able to adjust for
      lifestyle factors or other unmeasured confounders. CONCLUSIONS: In this study,
      women with hrHPV-positive cervical tumors had a substantially better prognosis
      than women with hrHPV-negative tumors. hrHPV appears to be a biomarker for better
      prognosis in cervical cancer independent of age, FIGO stage, and histological
      type, extending information from already established prognostic factors. The
      underlying biological mechanisms relating lack of detectable tumor hrHPV to
      considerably worse prognosis are not known and should be further investigated.

PMID- 30273339
TI  - Emergency presentation of colorectal patients in Spain.
AB  - BACKGROUND: Colorectal cancer (CRC) is the leading cause of cancer deaths in
      Europe. Survival is poorer in patients admitted to hospitals through the
      emergency department than in electively admitted patients. Knowledge of factors
      associated with a cancer diagnosis through presentation at an emergency
      department may reduce the likelihood of an emergency diagnosis. This study
      evaluated factors influencing the diagnosis of CRC in the emergency department.
      METHODS AND FINDINGS: This is a cross-sectional study in 5 Spanish regions;
      subjects were incident cases of CRC diagnosed in 9 public hospitals, between 2006
      and 2008. Data were obtained from patient interviews and primary care and
      hospital clinical records. We found that approximately 40% of CRC patients first
      contacted a hospital for CRC through an emergency service. Women were more likely
      than men to be emergency presenters. The type of symptom associated with
      emergency presentation differed between patients with colon cancer and those with
      rectal cancer, in that the frequency of "alarm symptoms" was significantly lower
      in colon than in rectal cancer patients who initially presented to emergency
      services. Soon after symptom onset, some patients went to a hospital emergency
      service, whereas others contacted their GP. Lack of contact with a GP for CRC
      related symptoms was consistently related to emergency presentation. Among
      patients who contacted a GP, a higher number of consultations for CRC symptoms
      and any referral to outpatient consultations reduced the likelihood of emergency
      presentation. All diagnostic time intervals were shorter in emergency presenters
      than in elective patients. CONCLUSIONS: Emergency presenters are not a uniform
      category and can be divided into categories according to their symptoms, help
      seeking behavior trajectory and interaction with their GPs. Time constraints for
      testing and delays in obtaining outpatient appointments led patients to visit a
      hospital service either on their own or after referral by their GP.

PMID- 30273341
TI  - Bile acids drive chemotaxis of Clonorchis sinensis juveniles to the bile duct.
AB  - Clonorchiasis is a neglected tropical disease caused by Chinese liver fluke,
      Clonorchis sinensis infection. C. sinensis is a biological carcinogen causing
      cholangiocarcinoma in humans. In the mammalian host, C. sinensis newly excysted
      juveniles (CsNEJs) migrate from the duodenum into the bile duct. Bile drives the
      chemotactic behavior of CsNEJs. Little is known about which components of bile
      induce the chemotaxis. We designed a chemotaxis assay panel and measured the
      chemotactic behavior of CsNEJs in response to bile or bile acids. The CsNEJs
      migrated toward 0.1-1% bile but away from 5-10% bile. The CsNEJs showed strong
      chemoattraction to cholic acid >=25 mM, but chemorepulsion to lithocholic acid
      >=0.25 mM. To the CsNEJs, mixture of cholic acid and lithocholic acid was
      chemoattractive at a ratio greater than 25:1 but chemorepulsive at one smaller
      than that. Regarding migration in the mammalian hosts, high concentration of
      lithocholic acid in the gallbladder bile may repel CsNEJs from entering it.
      However, bile in the hepatic bile duct has a chemoattractive strength of cholic
      acid but a trace amount of lithocholic acid. Collectively, our results explain
      why the CsNEJs migrate principally to the hepatic bile ducts, bypassing the
      gallbladder.

PMID- 30273342
TI  - Knowledge, attitudes and practices about human African trypanosomiasis and their
      implications in designing intervention strategies for Yei county, South Sudan.
AB  - BACKGROUND: A clear understanding of the knowledge, attitudes and practices (KAP)
      of a particular community is necessary in order to improve control of human
      African trypanosomiasis (HAT).New screening and diagnostic tools and strategies
      were introduced into South Sudan, as part of integrated delivery of primary
      healthcare. Knowledge and awareness on HAT, its new/improved screening and
      diagnostic tools, the places and processes of getting a confirmatory diagnosis
      and treatment are crucial to the success of this strategy. METHODOLOGY: A KAP
      survey was carried out in Yei County, South Sudan, to identify gaps in community
      KAP and determine the preferred channels and sources of information on the
      disease. The cross-sectional KAP survey utilized questionnaires, complemented
      with key informant interviews and a focus group discussion to elicit communal as
      well as individual KAP on HAT. FINDINGS: Most (90%) of the respondents had
      general knowledge on HAT. Lower levels of education, gender and geographic
      locations without a history of HAT interventions were associated with incorrect
      knowledge and/or negative perceptions about the treatability of HAT. Symptoms
      appearing in the late stage were best known. A majority (97.2%) would seek
      treatment for HAT only in a health centre. However, qualitative data indicates
      that existing myths circulating in the popular imagination could influence
      people's practices. Seventy-one percent of the respondents said they would offer
      social support to patients with HAT but qualitative data highlights that stigma
      still exists. Misconceptions and stigma can negatively influence the health
      seeking behaviour of HAT cases. In relation to communication, the top preferred
      and effective source of communication was radio (24%). CONCLUSION: Gaps in
      relation to KAP on HAT still exist in the community. Perceptions on HAT,
      specifically myths and stigma, were key gaps that need to be bridged through
      effective education and communication strategies for HAT control alongside other
      interventions.

PMID- 30273340
TI  - Stress susceptibility in Trypanosoma brucei lacking the RNA-binding protein
      ZC3H30.
AB  - Trypanosomes rely on post-transcriptional mechanisms and mRNA-binding proteins
      for control of gene expression. Trypanosoma brucei ZC3H30 is an mRNA-binding
      protein that is expressed in both the bloodstream form (which grows in mammals)
      and the procyclic form (which grows in the tsetse fly midgut). Attachment of
      ZC3H30 to an mRNA causes degradation of that mRNA. Cells lacking ZC3H30 showed no
      growth defect under normal culture conditions; but they were more susceptible
      than wild-type cells to heat shock, starvation, and treatment with DTT, arsenite
      or ethanol. Transcriptomes of procyclic-form trypanosomes lacking ZC3H30 were
      indistinguishable from those of cells in which ZC3H30 had been re-expressed, but
      un-stressed bloodstream forms lacking ZC3H30 had about 2-fold more HSP70 mRNA.
      Results from pull-downs suggested that ZC3H30 mRNA binding may not be very
      specific. ZC3H30 was found in stress-induced granules and co-purified with
      another stress granule protein, Tb927.8.3820; but RNAi targeting Tb927.8.3820 did
      not affect either ZC3H30 granule association or stress resistance. The
      conservation of the ZC3H30 gene in both monogenetic and digenetic kinetoplastids,
      combined with the increased stress susceptibility of cells lacking it, suggests
      that ZC3H30 confers a selective advantage in the wild, where the parasites are
      subject to temperature fluctuations and immune attack in both the insect and
      mammalian hosts.

PMID- 30273344
TI  - A facile hydrothermal approach for catalytic and optical behavior of tin oxide-
      graphene (SnO2/G) nanocomposite.
AB  - A cost-effective, facile hydrothermal approach was made for the synthesis of
      SnO2/graphene (Gr) nano-composites. XRD diffraction spectra clearly confirmed the
      presence of tetragonal crystal system of SnO2 which was maintaining its structure
      in both pure and composite materials' matrix. The stretching and bending
      vibrations of the functional groups were analyzed using FTIR analysis. FESEM
      images illustrated the surface morphology and the texture of the synthesized
      sample. HRTEM images confirmed the deposition of SnO2 nanoparticles over the
      surface of graphene nano-sheets. Raman Spectroscopic analysis was carried out to
      confirm the in-plane blending of SnO2 and graphene inside the composite matrix.
      The photocatalytic performance of the synthesized sample under UV irradiation
      using methylene blue dye was observed. Incorporation of grapheme into the SnO2
      sample had increased the photocatalytic activity compared with the pure SnO2
      sample. The electrochemical property of the synthesized sample was evaluated.

PMID- 30273343
TI  - Defining stopping criteria for ending randomized clinical trials that investigate
      the interruption of transmission of soil-transmitted helminths employing mass
      drug administration.
AB  - The current World Health Organization strategy to address soil-transmitted
      helminth (STH) infections in children is based on morbidity control through
      routine deworming of school and pre-school aged children. However, given that
      transmission continues to occur as a result of persistent reservoirs of infection
      in untreated individuals (including adults) and in the environment, in many
      settings such a strategy will need to be continued for very extended periods of
      time, or until social, economic and environmental conditions result in
      interruption of transmission. As a result, there is currently much discussion
      surrounding the possibility of accelerating the interruption of transmission
      using alternative strategies of mass drug administration (MDA). However, the
      feasibility of achieving transmission interruption using MDA remains uncertain
      due to challenges in sustaining high MDA coverage levels across entire
      communities. The DeWorm3 trial, designed to test the feasibility of interrupting
      STH transmission, is currently ongoing. In DeWorm3, three years of high treatment
      coverage-indicated by mathematical models as necessary for breaking transmission
      will be followed by two years of surveillance. Given the fast reinfection (bounce
      back) rates of STH, a two year no treatment period is regarded as adequate to
      assess whether bounce-back or transmission interruption have occurred in a given
      location. In this study, we investigate if criteria to determine whether
      transmission interruption is unlikely can be defined at earlier timepoints. A
      stochastic, individual-based simulation model is employed to simulate core
      aspects of the DeWorm3 community-based cluster-randomized trial. This trial
      compares a control arm (annual treatment of children alone with MDA) with an
      intervention arm (community-wide biannual treatment with MDA). Simulations were
      run for each scenario for both Ascaris lumbricoides and hookworm (Necator
      americanus). A range of threshold prevalences measured at six months after the
      last round of MDA and the impact of MDA coverage levels were evaluated to see if
      the likelihood of bounce-back or elimination could reliably be assessed at that
      point, rather than after two years of subsequent surveillance. The analyses
      suggest that all clusters should be assessed for transmission interruption after
      two years of surveillance, unless transmission interruption can be effectively
      ruled out through evidence of low treatment coverage. Models suggest a tight
      range of homogenous prevalence estimates following high coverage MDA across
      clusters which do not allow for discrimination between bounce back or
      transmission interruption within 24 months following cessation of MDA.

PMID- 30273345
TI  - Cost of chronic kidney disease attributable to diabetes from the perspective of
      the Brazilian Unified Health System.
AB  - INTRODUCTION: Diabetes is the most common cause of chronic kidney disease, with a
      high economic impact on health systems. OBJECTIVE: To estimate the cost of
      chronic kidney disease (CKD) and end-stage kidney disease (ESKD) attributable to
      diabetes, stratified by sex, race/skin color, and age, from the perspective of
      the Brazilian public health system between 2010 and 2016. METHODS: Population
      attributable risk (PAR) was calculated from the Brazilian prevalence of diabetes
      and the relative risk (or odds ratio) of persons with diabetes developing CKD and
      ESKD as compared to non-diabetic subjects. The variables of interest were sex,
      race/skin color, and age. A top-down approach was used to measure the direct
      costs of the disease reimbursed by the Brazilian Ministry of Health, using data
      from outpatient and inpatient records. RESULTS: The cost of CKD and ESKD
      attributable to diabetes in the period 2010-2016 was US$1.2 billion (US$180
      million per year) and trending upward. Female sex, age 65-75, and black race/skin
      color contributed substantially to the costs of CKD and ESKD (US$475 million,
      US$63 million, and US$25 million respectively). The clinical procedures
      accounting for the greatest share of disease-attributable costs are hemodialysis
      and peritoneal dialysis. CONCLUSION: Diabetes accounted for 22% of the costs of
      CKD and ESKD. Female sex, age 65-75 years, and black race/skin color were the
      variables which contributed most to disease-related expenditure. The economic
      burden of CKD may increase gradually in the coming years, with serious
      implications for the financial sustainability of the Brazilian public health
      system.

PMID- 30273346
TI  - An analysis of 3D knee kinematic data complexity in knee osteoarthritis and
      asymptomatic controls.
AB  - Three-dimensional (3D) knee kinematic data, measuring flexion/extension,
      abduction/adduction, and internal/external rotation angle variations during
      locomotion, provide essential information to diagnose, classify, and treat
      musculoskeletal knee pathologies. However, and so across genders, the curse of
      dimensionality, intra-class high variability, and inter-class proximity make this
      data usually difficult to interpret, particularly in tasks such as knee pathology
      classification. The purpose of this study is to use data complexity analysis to
      get some insight into this difficulty. Using 3D knee kinematic measurements
      recorded from osteoarthritis and asymptomatic subjects, we evaluated both single
      feature complexity, where each feature is taken individually, and global feature
      complexity, where features are considered simultaneously. These evaluations
      afford a characterization of data complexity independent of the used classifier
      and, therefore, provide information as to the level of classification performance
      one can expect. Comparative results, using reference databases, reveal that knee
      kinematic data are highly complex, and thus foretell the difficulty of knee
      pathology classification.

PMID- 30273347
TI  - The DEAD-box RNA-binding protein DDX6 regulates parental RNA decay for cellular
      reprogramming to pluripotency.
AB  - Cellular transitions and differentiation processes require mRNAs supporting the
      new phenotype but also the clearance of existing mRNAs for the parental
      phenotype. Cellular reprogramming from fibroblasts to induced pluripotent stem
      cells (iPSCs) occurs at the early stage of mesenchymal epithelial transition
      (MET) and involves drastic morphological changes. We examined the molecular
      mechanism for MET, focusing on RNA metabolism. DDX6, an RNA helicase, was
      indispensable for iPSC formation, in addition to RO60 and RNY1, a non-coding RNA,
      which form complexes involved in intracellular nucleotide sensing. RO60/RNY1/DDX6
      complexes formed prior to processing body formation, which is central to RNA
      metabolism. The abrogation of DDX6 expression inhibited iPSC generation, which
      was mediated by RNA decay targeting parental mRNAs supporting mesenchymal
      phenotypes, along with microRNAs, such as miR-302b-3p. These results show that
      parental mRNA clearance is a prerequisite for cellular reprogramming and that
      DDX6 plays a central role in this process.

PMID- 30273348
TI  - In vitro activity of N-acetylcysteine against Stenotrophomonas maltophilia and
      Burkholderia cepacia complex grown in planktonic phase and biofilm.
AB  - Stenotrophomonas maltophilia and Burkholderia cepacia complex (Bcc) have been
      increasingly recognized as relevant pathogens in hospitalized, immunocompromised
      and cystic fibrosis (CF) patients. As a result of complex mechanisms, including
      biofilm formation and multidrug resistance phenotype, S. maltophilia and Bcc
      respiratory infections are often refractory to therapy, and have been associated
      with a worse outcome in CF patients. Here we demonstrate for the first time that
      N-acetylcysteine (NAC), a mucolytic agent with antioxidant and anti-inflammatory
      properties, may exhibit antimicrobial and antibiofilm activity against these
      pathogens. The antimicrobial and antibiofilm activity of high NAC concentrations,
      potentially achievable by topical administration, was tested against a collection
      of S. maltophilia (n = 19) and Bcc (n = 19) strains, including strains from CF
      patients with acquired resistance traits. Minimum Inhibitory Concentrations
      (MICs) and Minimum Bactericidal Concentrations (MBCs) ranged from 16 to 32 mg/ml
      and from 32 to >32 mg/ml, respectively. Sub-MIC concentrations (i.e., 0.25 * MIC)
      slowed down the growth kinetics of most strains. In time-kill assays, 2-day-old
      biofilms were more affected than planktonic cultures, suggesting a specific
      antibiofilm activity of NAC against these pathogens. Indeed, a dose- and time
      dependent antibiofilm activity of NAC against most of the S. maltophilia and Bcc
      strains tested was observed, with a sizable antibiofilm activity observed also at
      0.5 and 1 * MIC NAC concentrations. Furthermore, at those concentrations, NAC was
      also shown to significantly inhibit biofilm formation with the great majority of
      tested strains.

PMID- 30273349
TI  - Statistical degradation modelling of Poly(D,L-lactide-co-glycolide) copolymers
      for bioscaffold applications.
AB  - This methodology permits to simulate the performance of different Poly(D,L
      lactide-co-glycolide) copolymer formulations (PDLGA) in the human body, to
      identify the more influencing variables on hydrolytic degradation and, thus, to
      estimate biopolymer degradation level. The PDLGA characteristic degradation
      trends, caused by hydrolysis processes, have been studied to define their future
      biomedical applications as dental scaffolds. For this purpose, the mass loss, pH,
      glass transition temperature (Tg) and absorbed water mass of the different
      biopolymers have been obtained from samples into a phosphate-buffered saline
      solution (PBS) with initial pH of 7.4, at 37 degrees C (human body conditions).
      The mass loss has been defined as the variable that characterize the biopolymer
      degradation level. Its dependence relationship with respect to time, pH and
      biopolymer formulation has been modelled using statistical learning tools.
      Namely, generalized additive models (GAM) and nonlinear mixed-effects regression
      with logistic and asymptotic functions have been applied. GAM model provides
      information about the relevant variables and the parametric functions that relate
      mass loss, pH and time. Mixed effects are introduced to model and estimate the
      degradation properties, and to compare the PDLGA biopolymer populations. The
      degradation path for each polymer formulation has been estimated and compared
      with respect to the others for helping to use the proper polymer for each
      specific medical application, performing selection criteria. It was found that
      the mass loss differences in PDLGA copolymers are strongly related with the way
      the pH decay versus time, due to carboxylic acid groups formation. This may occur
      in those environments in which the degradation products remain relatively
      confined with the non degraded mass. This is the case emulated with the present
      experimental procedure. The results show that PDLGA polymers degradation degree,
      in terms of half life and degradation rate, is increasing when acid termination
      is included, when DL-lactide molar ratio is reduced, decreasing the midpoint
      viscosity, or when glycolide is not included.

PMID- 30273350
TI  - STLV-1 co-infection is correlated with an increased SFV proviral load in the
      peripheral blood of SFV/STLV-1 naturally infected non-human primates.
AB  - Simian T-Leukemia Virus type 1 and Simian Foamy Virus infect non-human primates.
      While STLV-1, as HTLV-1, causes Adult T-cell Leukemia/lymphoma, SFV infection is
      asymptomatic. Both retroviruses can be transmitted from NHPs to humans through
      bites that allow contact between infected saliva and recipient blood. Because
      both viruses infect CD4+ T-cells, they might interfere with each other
      replication, and this might impact viral transmission. Impact of STLV-1 co
      infection on SFV replication was analyzed in 18 SFV-positive/STLV-1-negative and
      18 naturally SFV/STLV-1 co-infected Papio anubis. Even if 9 animals were found
      STLV-1-positive in saliva, STLV-1 PVL was much higher in the blood. SFV
      proviruses were detected in the saliva of all animals. Interestingly, SFV
      proviral load was much higher in the blood of STLV-1/SFV co-infected animals,
      compared to STLV-1-negative animals. Given that soluble Tax protein can enter
      uninfected cells, we tested its effect on foamy virus promoter and we show that
      Tax protein can transactivate the foamy LTR. This demonstrates that true STLV-1
      co-infection or Tax only has an impact on SFV replication and may influence the
      ability of the virus to be zoonotically transmitted as well as its ability to
      promote hematological abnormalities.

PMID- 30273351
TI  - Beta-adrenergic activation induces cardiac collapse by aggravating cardiomyocyte
      contractile dysfunction in bupivacaine intoxication.
AB  - In order to determine the role of the adrenergic system in bupivacaine-induced
      cardiotoxicity, a series of experiments were performed. In an animal experiment,
      male Sprague-Dawley (SD) rats under chloral hydrate anesthesia received
      intravenous bupivacaine, followed by an intravenous injection of adrenalin or
      isoprenalin, and the electrocardiogram (ECG), left ventricular systolic pressure
      (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum rate of rise
      of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure
      decrease (-dP/dtmax) were continually monitored. In a cellular experiment,
      freshly isolated adult SD rat ventricular myocytes were perfused with bupivacaine
      at different concentrations in the presence or absence of isoprenalin, with or
      without esmolol. The percentage of the sarcomere shortening (bl% peak h),
      departure velocity (dep v) of sarcomere shortening and time to 50% of the peak
      speed of myocyte contraction (Tp50) was assessed by a video-based edge-detection
      system. In an additional experiment, Swiss mice pretreated with saline,
      isoprenalin, esmolol or dexmedetomidine received bupivacaine to determine the 50%
      lethal dose (LD50) of bupivacaine. Electron microscopy of myocardial mitochondria
      was performed to assess damage of these structures. To test mitochondrial
      reactive oxygen species (ROS) production, freshly isolated SD rat ventricular
      myocytes were incubated with bupivacaine in the presence of isoprenalin, with or
      without esmolol. First, our results showed that bupivacaine significantly reduced
      the LVSP and +dP/dtmax, as well as enhanced the LVEDP and -dP/dtmax (P < 0.05,
      vs. control, and vs. baseline). Adrenalin and isoprenalin induced a further
      reduction of LVSP and +dP/dtmax (P < 0.05, vs. before adrenalin or isoprenalin
      delivery, and vs. control). Second, bupivacaine induced a dose-dependent
      cardiomyocyte contractile depression. While 5.9 MUmol/L or 8.9 MUmol/L of
      bupivacaine resulted in no change, 30.0 MUmol/L of bupivacaine prolonged the Tp50
      and reduced the bl% peak h and dep v (P < 0.05, vs. control and vs. baseline).
      Isoprenalin aggravated the bupivacaine-induced cardiomyocyte contractile
      depression, significantly prolonging the Tp50 (P < 0.05, vs. bupivacaine alone)
      and reducing the dep v (P < 0.05, vs. bupivacaine alone). Third, esmolol and
      dexmedetomidine significantly enhanced, while isoprenalin significantly reduced,
      the LD50 of bupivacaine in mice. Fourth, bupivacaine led to significant
      mitochondrial swelling, and the extent of myocardial mitochondrial swelling in
      isoprenalin-pretreated mice was significantly higher than that compared with mice
      pretreated with saline, as reflected by the higher mitochondrial damage score (P
      < 0.01). Meanwhile, esmolol pretreatment significantly reduced the mitochondrial
      damage score (P < 0.01). Fifth, bupivacaine significantly increased the ROS in
      freshly isolated cardiomyocytes, and added isoprenalin induced a further
      enhancement of ROS production (P < 0.05, vs. bupivacaine alone). Added esmolol
      significantly decreased ROS production (P < 0.05, vs. bupivacaine + isoprenalin).
      Our results suggest that bupivacaine depressed cardiac automaticity, conductivity
      and contractility, but the predominant effect was contractile dysfunction which
      resulted from the disruption of mitochondrial energy metabolism. beta-adrenergic
      activation aggravated the cellular metabolism disorder and therefore contractile
      dysfunction.

PMID- 30273352
TI  - Quantification of dengue virus specific T cell responses and correlation with
      viral load and clinical disease severity in acute dengue infection.
AB  - BACKGROUND: In order to understand the role of dengue virus (DENV) specific T
      cell responses that associate with protection, we studied their frequency and
      phenotype in relation to clinical disease severity and resolution of viraemia in
      a large cohort of patients with varying severity of acute dengue infection.
      METHODOLOGY/PRINCIPAL FINDINGS: Using ex vivo IFNgamma ELISpot assays we
      determined the frequency of dengue viral peptide (DENV)-NS3, NS1 and NS5
      responsive T cells in 74 adult patients with acute dengue infection and examined
      the association of responsive T cell frequency with the extent of viraemia and
      clinical disease severity. We found that total DENV-specific and DENV-NS3
      specific T cell responses, were higher in patients with dengue fever (DF), when
      compared to those with dengue haemorrhagic fever (DHF). In addition, those with
      DF had significantly higher (p = 0.02) DENV-specific T cell responses on day 4 of
      infection compared to those who subsequently developed DHF. DENV peptide specific
      T cell responses inversely correlated with the degree of viraemia, which was most
      significant for DENV-NS3 specific T cell responses (Spearman's r = -0.47, p =
      0.0003). The frequency of T cell responses to NS1, NS5 and pooled DENV peptides,
      correlated with the degree of thrombocytopenia but had no association with levels
      of liver transaminases. In contrast, total DENV-IgG inversely correlated with the
      degree of thrombocytopenia and levels of liver transaminases.
      CONCLUSIONS/SIGNIFICANCE: Early appearance of DENV-specific T cell IFNgamma
      responses before the onset of plasma leakage, appears to associate with milder
      clinical disease and resolution of viraemia, suggesting a protective role in
      acute dengue infection.

PMID- 30273355
TI  - Cross-cultural emotion recognition and evaluation of Radboud faces database with
      an Indian sample.
AB  - Emotional databases are important tools to study emotion recognition and their
      effects on various cognitive processes. Since, well-standardized large-scale
      emotional expression database is not available in India, we evaluated Radboud
      faces database (RaFD)-a freely available database of emotional facial expressions
      of adult Caucasian models, for Indian sample. Using the pictures from RaFD, we
      investigated the similarity and differences in self-reported ratings on emotion
      recognition accuracy as well as parameters of valence, clarity, genuineness,
      intensity and arousal of emotional expression, by following the same rating
      procedure as used for the validation of RaFD. We also systematically evaluated
      the universality hypothesis of emotion perception by analyzing differences in
      accuracy and ratings for different emotional parameters across Indian and Dutch
      participants. As the original Radboud database lacked arousal rating, we added
      this as a emotional parameter along with all other parameters. The results show
      that the overall accuracy of emotional expression recognition by Indian
      participants was high and very similar to the ratings from Dutch participants.
      However, there were significant cross-cultural differences in classification of
      emotion categories and their corresponding parameters. Indians rated certain
      expressions comparatively more genuine, higher in valence, and less intense in
      comparison to original Radboud ratings. The misclassifications/ confusion for
      specific emotional categories differed across the two cultures indicating subtle
      but significant differences between the cultures. In addition to understanding
      the nature of facial emotion recognition, this study also evaluates and enables
      the use of RaFD within Indian population.

PMID- 30273354
TI  - Cooperation of dual modes of cell motility promotes epithelial stress relaxation
      to accelerate wound healing.
AB  - Collective cell migration in cohesive units is vital for tissue morphogenesis,
      wound repair, and immune response. While the fundamental driving forces for
      collective cell motion stem from contractile and protrusive activities of
      individual cells, it remains unknown how their balance is optimized to maintain
      tissue cohesiveness and the fluidity for motion. Here we present a cell-based
      computational model for collective cell migration during wound healing that
      incorporates mechanochemical coupling of cell motion and adhesion kinetics with
      stochastic transformation of active motility forces. We show that a balance of
      protrusive motility and actomyosin contractility is optimized for accelerating
      the rate of wound repair, which is robust to variations in cell and substrate
      mechanical properties. This balance underlies rapid collective cell motion during
      wound healing, resulting from a tradeoff between tension mediated collective cell
      guidance and active stress relaxation in the tissue.

PMID- 30273353
TI  - meaRtools: An R package for the analysis of neuronal networks recorded on
      microelectrode arrays.
AB  - Here we present an open-source R package 'meaRtools' that provides a platform for
      analyzing neuronal networks recorded on Microelectrode Arrays (MEAs). Cultured
      neuronal networks monitored with MEAs are now being widely used to characterize
      in vitro models of neurological disorders and to evaluate pharmaceutical
      compounds. meaRtools provides core algorithms for MEA spike train analysis,
      feature extraction, statistical analysis and plotting of multiple MEA recordings
      with multiple genotypes and treatments. meaRtools functionality covers novel
      solutions for spike train analysis, including algorithms to assess electrode
      cross-correlation using the spike train tiling coefficient (STTC), mutual
      information, synchronized bursts and entropy within cultured wells. Also
      integrated is a solution to account for bursts variability originating from mixed
      cell neuronal cultures. The package provides a statistical platform built
      specifically for MEA data that can combine multiple MEA recordings and compare
      extracted features between different genetic models or treatments. We demonstrate
      the utilization of meaRtools to successfully identify epilepsy-like phenotypes in
      neuronal networks from Celf4 knockout mice. The package is freely available under
      the GPL license (GPL> = 3) and is updated frequently on the CRAN web-server
      repository. The package, along with full documentation can be downloaded from:
      https://cran.r-project.org/web/packages/meaRtools/.

PMID- 30273356
TI  - Same or different? Theory of mind among children with and without disabilities.
AB  - Assessing theory of mind (ToM) with reliable and valid measures is important, as
      ToM plays a significant role in children's social and cognitive functioning. With
      this in mind, a thorough analysis of the Theory of Mind scale and the Faux Pas
      Recognition Test was conducted. Over 750 school-age (M age = 7.7) children with
      disabilities (mild intellectual disability, hearing impairment) and without
      disabilities took part in our study. The psychometric properties of measures in
      these groups of children were checked, using confirmatory item factor analysis,
      reliability, and validity analyses. Thanks to groups' invariance it was possible
      to compare mean results of children in the groups. Both measures showed well
      fitted models with acceptable goodness of fit as well as scalar and strict
      invariance. An IRT analysis showed significant differences in the difficulty of
      the tasks in all groups, but the same order of passing tasks in comparison to
      other studies, conducted in Western countries, has been observed. Our results
      showed that the tasks were the easiest for children without disabilities, and
      most difficult for children with mild intellectual disability. We obtained
      significant and positive correlations between ToM and social skills and language
      abilities. The findings are discussed in relation to results from other studies
      in the field.

PMID- 30273357
TI  - The predictors for the non-compliance to follow-up among very low birth weight
      infants in the Korean neonatal network.
AB  - The critical need to emphasize preterm infant follow-up after neonatal intensive
      care unit (NICU) discharge assures early identification of and intervention for
      neurodevelopmental disability. The aims of this study were to observe the follow
      up rates in high-risk follow-up clinics, and analyze factors associated with non
      compliance to follow-up among very low birth weight (VLBW) infants. The data was
      prospectively collected for 3063 VLBW infants between January 2013 and December
      2014 from 57 Korean neonatal network (KNN) centers at a corrected age of 18-24
      months. Correlations among demographic data, clinical variables, and neonatal
      intensive care unit (NICU) volume (divided into 4 quartiles) with the occurrence
      of non-compliance were analyzed. The overall follow-up rate at the corrected age
      of 18-24 month was 65.4%. The follow-up rates were inversely related to birth
      weight and gestational age. Apgar score, hospital stay, maternal age, and
      maternal education were significantly different between the compliance and non
      compliance groups. The follow-up rate was higher for mothers with
      chorioamnionitis, abnormal amniotic fluid, multiple pregnancy, and in vitro
      fertilization. Infants with respiratory distress syndrome, bronchopulmonary
      dysplasia, patent ductus arteriosus ligation, periventricular leukomalacia, and
      retinopathy of prematurity were more common in the compliance group. Follow-up
      rates showed significant differences according to NICU volume. Using multivariate
      logistic regression, high birth weight, low NICU volume, siblings, foreign
      maternal nationality and high 5 min APGAR scores were significant independent
      factors associated with the non-compliance of VLBW infants for follow-up at 18-24
      months of age. This is the first nation-wide analysis of follow-up for VLBW
      infants in Korea. Understanding factors associated with failure of compliance
      could help improve the long-term follow-up rates and neurodevelopmental outcomes
      through early intervention.

PMID- 30273358
TI  - Mass spectrometry-based lipidomics to explore the biochemical effects of
      naphthalene toxicity or tolerance in a mouse model.
AB  - Naphthalene causes mouse airway epithelial injury. However, repeated exposures of
      naphthalene result in mouse airway tolerance. Previous results showed that
      toxicity or tolerance was correlated with changes of phosphorylcholine-containing
      lipids. In this study, a mass spectrometry-based lipidomic approach was applied
      to examine the effects of naphthalene-induced injury or tolerance in the male ICR
      mice. The injury model was vehicle x 7 plus 300 mg/kg naphthalene while the
      tolerant one was 200 mg/kg daily x 7 followed by 300 mg/kg naphthalene on day 8.
      The lung, liver, kidney, and serum samples were collected for profiles of
      phosphorylcholine-containing lipids including phosphatidylcholines (PCs) and
      sphingomyelins (SMs). A partial least-square-discriminate analysis model showed
      different lung phosphorylcholine-containing lipid profiles from the injured,
      tolerant, and control groups. Perturbation of diacyl-PCs and plasmenylcholines
      may be associated with enhanced membrane flexibility and anti-oxidative
      mechanisms in the lungs of tolerant mice. Additionally, alterations of lyso-PCs
      and SMs may be responsible for pulmonary dysfunction and inflammation in the
      lungs of injured mice. Moreover, serum PC(16:0/18:1) has potential to reflect
      naphthalene-induced airway injuries. Few phosphorylcholine-containing lipid
      alterations were found in the mouse livers and kidneys across different
      treatments. This study revealed the changes in lipid profiles associated with the
      perturbations caused by naphthalene tolerance and toxicity; examination of lipids
      in serum may assist biomarker development with the potential for application in
      the human population.

PMID- 30273359
TI  - Inflammation-associated miR-155 activates differentiation of muscular satellite
      cells.
AB  - Tissue renewal and muscle regeneration largely rely on the proliferation and
      differentiation of muscle stem cells called muscular satellite cells (MuSCs).
      MuSCs are normally quiescent, but they are activated in response to various
      stimuli, such as inflammation. Activated MuSCs proliferate, migrate,
      differentiate, and fuse to form multinucleate myofibers. Meanwhile, inappropriate
      cues for MuSC activation induce premature differentiation and bring about stem
      cell loss. Recent studies revealed that stem cell regulation is disrupted in
      various aged tissues. We found that the expression of microRNA (miR)-155, which
      is an inflammation-associated miR, is upregulated in MuSCs of aged muscles, and
      this upregulation activates the differentiation process through suppression of
      C/ebpbeta, which is an important molecule for maintaining MuSC self-renewal. We
      also found that Notch1 considerably repressed miR-155 expression, and loss of
      Notch1 induced miR-155 overexpression. Our findings suggest that miR-155 can act
      as an activator of muscular differentiation and might be responsible for
      accelerating aging-associated premature differentiation of MuSCs.

PMID- 30273360
TI  - Preventative effects of resveratrol and estradiol on streptozotocin-induced
      diabetes in ovariectomized mice and the related mechanisms.
AB  - Resveratrol, a non-flavonoid polyphenolic compound, is structurally and
      functionally similar to estrogen and has drawn great attention for its
      potentially beneficial effects on diabetes. However, it is not known whether it
      shares the same protective effect against diabetes as estrogen and the underlying
      mechanisms. The aim of the present study was to investigate the protective
      effects of phytoestrogen resveratrol and exogenous 17beta-estradiol against
      streptozotocin (STZ)-induced type 1 diabetes. Female mice were ovariectomized
      (OVX) and chronically injected with different concentrations of resveratrol (0.1,
      1 or 10 mg/kg) and 17beta-estradiol (0.01, 0.1 or 1 mg/kg) subcutaneously for 4
      weeks, and the levels of blood glucose, plasma insulin, plasma antioxidant
      capacity, the changes of pancreatic islet cells and the expressions of glucose
      transporter 4 (GLUT4), insulin receptor substrate 1 (IRS-1) and phosphorylation
      of extracellular signal-regulated kinase (p-ERK) were detected. Resveratrol and
      17beta-estradiol significantly inhibited the increase of the blood glucose level
      and the rise of plasma malondialdehyde in STZ-induced diabetic mice, improved the
      levels of plasma antioxidant capacity and plasma insulin, protected the
      pancreatic islet cells, and increased the expressions of GLUT4 and IRS-1, but
      decreased p-ERK expression in skeletal muscle and myocardial tissue. The results
      suggest that resveratrol or 17beta-estradiol shows obvious protection against STZ
      induced diabetes in OVX mice, the mechanisms probably involve their ameliorating
      antioxidant activities and islet function, promoting muscle glucose uptake and
      inhibiting the expression of p-ERK.

PMID- 30273361
TI  - Cytoprotective effect of 2-carbomethoxy-2,3-epoxy-3-prenyl-1,4-naphthoquinone
      (CMEP-NQ) is mediated by the inhibition of BAK-dependent mitochondrial apoptosis
      pathway.
AB  - The inhibitory mechanism of 2-carbomethoxy-2,3-epoxy-3-prenyl-1,4-naphthoquinone
      (CMEP-NQ) against apoptosis induced by the microtubule-damaging agents (MDAs),
      nocodazole (NOC) and 2-methoxyestradiol (2-MeO-E2), or a DNA-damaging agent
      (DDA), camptothecin (CPT) were investigated in human Jurkat T cell clones (J/Neo
      and J/BCL-XL cells). Treatment of J/Neo cells with NOC, 2-MeO-E2, or CPT caused
      cytotoxicity and apoptotic DNA fragmentation but these events were significantly
      attenuated in the presence of CMEP-NQ. Although not only MDA (NOC or 2-MeO-E2)
      induced mitotic arrest, CDK1 activation, and BCL-2, BCL-XL and BIM
      phosphorylation, but also DDA (CPT)-induced S-phase arrest and ATM-CHK1/CHK2-p53
      pathway activation were not or were barely affected in the presence of CMEP-NQ,
      the levels of anti-apoptotic BAG3 and MCL-1, which were markedly downregulated
      after MDA- or DDA-treatment, were rather elevated by CMEP-NQ. Under the same
      conditions, MDA- or DDA-induced mitochondrial apoptotic events including BAK
      activation, mitochondrial membrane potential (Deltapsim) loss, caspase-9
      activation, and PARP cleavage were significantly inhibited by CMEP-NQ. While MDA-
      or DDA-induced sub-G1 peak and Deltapsim loss were abrogated in J/BCL-XL cells,
      MDA-induced mitotic arrest and DDA-induced S-arrest were more apparent in J/BCL
      XL cells than in J/Neo cells. Simultaneously, the induced cell cycle arrest in
      J/BCL-XL cells was not significantly disturbed by CMEP-NQ. MDA- or DDA-treatment
      caused intracellular reactive oxygen species (ROS) production; however, MDA- or
      DDA-induced ROS production was almost completely abrogated in J/BCL-XL cells. MDA
      or DDA-induced ROS production in J/Neo cells was significantly suppressed by
      CMEP-NQ, but the suppressive effect was hardly observed in J/BCL-XL cells.
      Together, these results show that CMEP-NQ efficiently protects Jurkat T cells
      from apoptotic cell death via the elevation of BAG3 and MCL-1 levels, which
      results in the inhibition of intrinsic BAK-dependent mitochondrial apoptosis
      pathway, as does the overexpression of BCL-XL.

PMID- 30273362
TI  - Isothermal amplification and rapid detection of Klebsiella pneumoniae based on
      the multiple cross displacement amplification (MCDA) and gold nanoparticle
      lateral flow biosensor (LFB).
AB  - Klebsiella pneumoniae (K. pneumoniae) is a frequent pathogen causing nosocomial
      infections and outbreaks. We developed a multiple cross displacement
      amplification (MCDA) assay for the detection of K. pneumoniae, which can get the
      positive results within 40 minutes' isothermal amplification. Gold-nanoparticle
      lateral flow biosensor (LFB) and colorimetric indicators were used for the rapid
      readouts of MCDA amplification. The detection limit of this assay was 100 fg per
      reaction at 65 degrees C, which was confirmed to be the optimal amplification
      temperature according to the real time turbidimeters. For specificity, all of the
      30 clinical-source K. pneumoniae strains were positive for the MCDA, and all of
      the non-K. pneumoniae strains belonging to 31 different species were negative for
      this MCDA assay. To evaluate the practical applicability of this method, we
      assessed its detection limit for K. pneumoniae strains in sputum samples (24 CFU
      per reaction), and DNA templates of 100 sputum samples further underwent the MCDA
      LFB tests. All of the sputum samples being positive for K. pneumoniae (30/100)
      with the culture method were successfully identified with the MCDA assay, the
      detection power of which was higher than that of polymerase chain reaction (PCR)
      (25/100). Thus, the MCDA test for K. pneumoniae combined with the gold
      nanoparticle LFB as the results readout scheme, are simple, specific, and
      sensitive methods for the rapid diagnosis of K. pneumoniae in clinical samples.

PMID- 30273363
TI  - Chronic obstructive pulmonary disease and periprocedural complications in
      patients undergoing percutaneous coronary interventions.
AB  - BACKGROUND: The relationship between chronic obstructive pulmonary disease (COPD)
      and periprocedural complications of percutaneous coronary interventions (PCIs) is
      influenced by several factors. We aimed to investigate the association between
      COPD, its complication type and rate in patients undergoing PCI. METHODS: Data
      were prospectively collected using the Polish Cardiovascular Intervention Society
      national registry (ORPKI) on all PCIs performed in Poland between January 2015
      and December 2016. COPD was present in 5,594 of the 221,187 patients undergoing
      PCI. We assessed the frequency and predictors of periprocedural complications in
      PCI. RESULTS: Patients with COPD were elder individuals (70.3 +/- 9.9 vs. 67 +/-
      10.8 years; p < 0.05). We noted 145 (2.6%) periprocedural complications in the
      COPD group and 4,121 (1.9%) in the non-COPD group (p < 0.001). The higher
      incidence of periprocedural complications in the COPD patients was mainly
      attributed to cardiac arrest (p = 0.001), myocardial infarctions (p = 0.002) and
      no-reflows (p < 0.001). COPD was not an independent predictor of all
      periprocedural complications. On the other hand, COPD was found to be an
      independent predictor of increased no-reflow risk (odds ratio [OR] 1.447, 95% CI
      1.085-1.929; p = 0.01), and at the same time, of decreased risk of periprocedural
      allergic reactions (OR 0.117, 95% CI 0.016-0.837; p = 0.03). CONCLUSIONS: In
      conclusion, periprocedural complications of PCIs are more frequent in patients
      with COPD. COPD is an independent positive predictor of no-reflow and a negative
      predictor of periprocedural allergic reactions.

PMID- 30273364
TI  - Obesity alters composition and diversity of the oral microbiota in patients with
      type 2 diabetes mellitus independently of glycemic control.
AB  - BACKGROUND AND OBJECTIVE: The involvement of the oral microbiota as a possible
      link between periodontitis, type 2 diabetes mellitus and obesity is still not
      well understood. The objective of the study was to investigate if glycemic
      control and obesity play a role in modulating the composition and diversity of
      the oral microbial ecology. MATERIAL AND METHODS: A cohort of patients with type
      2 diabetes mellitus (n = 18) was recruited. Participants demonstrating improved
      glycemic control after 3 months (n = 6) were included in a second examination. A
      full mouth examination was performed to estimate periodontitis severity followed
      by sample collection (subgingival plaque and saliva). Generation of large
      sequence libraries was performed using the high-throughput Illumina MiSeq
      sequencing platform. RESULTS: The majority of participants (94.4%, n = 17)
      presented with moderate or severe forms of periodontitis. Differences in
      microbial composition and diversity between obese (BMI >= 30 kg/m2) and non-obese
      (BMI < 30 kg/m2) groups were statistically significant. Cross-sectional and
      longitudinal approaches failed to reveal statistically significant associations
      between HbA1c level and species composition or diversity. CONCLUSIONS: Obesity
      was significantly associated with the oral microbial composition. The impact of
      glycemic control on oral microbiota, however, could not be assured statistically.

PMID- 30273365
TI  - A novel biomarker of laminin turnover is associated with disease progression and
      mortality in chronic kidney disease.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) have increased risk of
      development of end-stage renal disease (ESRD) and early mortality. Fibrosis is
      the central pathogenic process in CKD and is caused by dysregulated extracellular
      matrix (ECM) remodeling. The laminin gamma1 chain (LAMC1) is a core structural
      protein present in the basement membrane of several organs, including the
      kidneys. We hypothesized that dysregulation of LAMC1 remodeling could be
      associated with a higher risk of adverse clinical outcomes in patients with CKD.
      METHODS: A novel immunoassay targeting LG1M, a specific MMP-9-generated neo
      epitope fragment of LAMC1, was developed and used to measure the levels of the
      fragment in urine and serum from 492 patients from the Renal Impairment in
      Secondary Care (RIISC) study, a prospective cohort of patients with high-risk
      CKD. Patients were monitored for a median follow-up time of 3.5 years.
      Associations between serum and urine LG1M levels and progression of CKD at 12
      months were assessed by a multivariable logistic regression model. The
      association with ESRD or mortality was assessed by Kaplan-Meier survival curves
      and Cox proportional hazards regression. RESULTS: Forty-six (11%) of the 416
      patients who reached 12-month follow-up had progression of CKD; during the study
      follow-up, 125 patients (25.4%) developed ESRD and 71 patients (14.4%) died.
      Serum and urine levels of LG1M correlated with baseline eGFR (r = -0.43, p<0.0001
      and r = -0.17, p = 0.0002, respectively). Serum levels of LG1M were higher in
      patients with one-year progression of CKD compared to those who did not progress
      (p<0.01). Baseline serum levels of LG1M were associated with development of ESRD
      (HR 3.2, 95% CI 1.99-5.2 for patients in the highest LG1M tertile compared to
      patient in the lowest tertile). Baseline urinary levels of LG1M (uLG1M) were
      significantly associated with mortality (HR 5.0, 95% CI 2.8-8.9, p<0.0001 for
      patients in the highest LG1M tertile compared to patients in the lowest tertile).
      Urine LG1M was retained in the model for prediction of mortality (HR per standard
      deviation of uLG1M: 1.01, 95% CI 1.00-1.02, p = 0.001). CONCLUSIONS: LG1M, a
      marker of basement membrane remodeling, is increased in serum and urine of
      patients with CKD and levels are associated with one-year disease progression,
      development of ESRD, and mortality.

PMID- 30273366
TI  - Gelatinase B/matrix metalloproteinase-9 is a phase-specific effector molecule,
      independent from Fas, in experimental autoimmune encephalomyelitis.
AB  - Gelatinase B/matrix metalloproteinase-9 (MMP-9) triggers multiple sclerosis (MS)
      and the animal model of experimental autoimmune encephalomyelitis (EAE) by the
      breakdown of the blood-brain barrier. Interestingly, MMP-9 is beneficial in
      systemic autoimmunity caused by Fas-deficiency. Fas-deficient (faslpr) and Fas
      ligand-deficient mice are protected against EAE. We here investigated the
      interaction between Fas and MMP-9 in the setting of induction of EAE and compared
      short- and long-term effects. We provoked EAE with myelin oligodendrocyte
      glycoprotein (MOG) peptide and compared EAE development in four genotypes (wild
      type (WT), single knockout mmp-9-/-, faslpr, and mmp-9-/-/faslpr) and monitored
      leukocytes, cytokines and chemokines as immunological parameters. As expected,
      faslpr mice were resistant against EAE induction, whereas MMP-9 single knockout
      mice were not. In the double mmp-9-/-/ faslpr mice the effects on disease scores
      pointed to independent rather than interrelated disease mechanisms. On a short
      term, after EAE induction leukocytes infiltrated into the brain and cytokine and
      chemokine levels were significantly higher in all the four genotypes studied,
      even in the faslpr and mmp-9-/-/faslpr, which did not develop clinical disease.
      The levels of MMP-9 but not of MMP-2 were increased in the brain and in the
      peripheral organs after EAE induction. After 40 days all the animals recovered
      and did not show signs of EAE. However, the absence of MMP-9 in the remission
      phase suggested a protective role of MMP-9 in the late phase of the disease,
      because single mmp-9-/- mice presented a delayed remission in comparison with WT
      animals suggesting a phase-dependent role of MMP-9 in the disease. Nevertheless,
      the levels of some cytokines and chemokines remained higher than in control
      animals even 100 days after EAE induction, attesting to a prolonged state of
      immune activation. We thus yielded new insights and useful markers to monitor
      this activated immune status. Furthermore, MMP-9 but not MMP-2 levels remained
      increased in the brains and, to a higher extend, in the spleens of the WT mice
      even during the remission phase, which is in line with the role of MMP-9 as a
      useful marker and a protective factor for EAE in the remission phase.

PMID- 30273367
TI  - Evaluating the temporal and situational consistency of personality traits in
      adult dairy cattle.
AB  - Recent research suggests that personality, defined as consistent individual
      behavioral variation, in farm animals could be an important factor when
      considering their health, welfare, and productivity. However, behavioral tests
      are often performed individually and they might not reflect the behavioral
      differences manifested in every-day social environments. Furthermore, the
      contextual and longer-term temporal stability of personality traits have rarely
      been investigated in adult dairy cattle. In this study, we tested three groups of
      lactating Holstein cows (40 cows) using an individual arena test and a novel
      object test in groups to measure the contextual stability of behavior. Among the
      recorded individual test parameters, we used seven in the final analysis, which
      were determined by a systematic parameter reduction procedure. We found positive
      correlations between novel object contact duration in the group test and
      individual test parameters object contact duration (Rs = 0.361, P = 0.026) and
      movement duration (Rs = 0.336, P = 0.039). Both tests were repeated 6 months
      later to investigate their temporal stability whereby four individual test
      parameters were repeatable. There was no consistency in the group test results
      for 25 cows tested twice, possibly due to group composition changes. Furthermore,
      based on the seven individual test parameters, two personality traits
      (activity/exploration and boldness) were identified by principal component
      analysis. We found a positive association between the first and second tests for
      activity/exploration (Rs = 0.334, P = 0.058) and for boldness (Rs = 0.491, P =
      0.004). Our results support the multidimensional nature of personality in adult
      dairy cattle and they indicate a link between behavior in individual and within
      group situations. The lack of stability according to the group test results
      implies that group companions might have a stronger influence on individual
      behavior than expected. We suggest repeating the within-group behavioral
      measurements to study the relationship between the social environment and the
      manifestation of personality traits in every-day situations.

PMID- 30273368
TI  - Influence of peer networks on physician adoption of new drugs.
AB  - Although physicians learn about new medical technologies from their peers, the
      magnitude and source of peer influence is unknown. We estimate the effect of peer
      adoption of three first-in-class medications (dabigatran, sitigliptin, and
      aliskiren) on physicians' own adoption of those medications. We included 11,958
      physicians in Pennsylvania prescribing anticoagulant, antidiabetic, and
      antihypertensive medications. We constructed 4 types of peer networks based on
      shared Medicare and Medicaid patients, medical group affiliation, hospital
      affiliation, and medical school/residency training. Instrumental variables
      analysis was used to estimate the causal effect of peer adoption (fraction of
      peers in each network adopting the new drug) on physician adoption (prescribing
      at least the median number prescriptions within 15 months of the new drug's
      introduction). We illustrate how physician network position can inform targeting
      of interventions to physicians by computing a social multiplier. Dabigatran was
      adopted by 25.2%, sitagliptin by 24.5% and aliskiren by 8.3% of physicians. A 10
      percentage point increase in peer adoption in the patient-sharing network led to
      a 5.90% (SE = 1.50%, p<0.001) increase in physician adoption of dabigatran, 8.32%
      (SE = 1.51%, p<0.001) increase in sitagliptin, and 7.84% increase in aliskiren
      adoption (SE = 2.93%, p<0.001). Peer effects through shared hospital affiliation
      were positive but not significant, and medical group and training network effects
      were not reliably estimated. Physicians in the top decile of patient-sharing
      network peers were estimated to have nearly 2-fold stronger influence on their
      peers' adoption compared to physicians in the top decile of prescribing volume.
      Limitations include lack of detailed clinical information and pharmaceutical
      promotion, variables which may influence physician adoption but which are
      unlikely to bias our peer effect estimates. Peer adoption, especially by those
      with whom physicians share patients, strongly influenced physician adoption of
      new drugs. Our study shows the potential for using information on physician peer
      networks to improve technology diffusion.

PMID- 30273369
TI  - Pharmacogenetic variation influences sensory neuropathy occurrence in Southern
      Africans treated with stavudine-containing antiretroviral therapy.
AB  - BACKGROUND: The use of the HIV antiretroviral drug stavudine (d4T), a thymidine
      analogue, is associated with the development of mitochondrial toxicities such as
      sensory neuropathy (SN). Genetic variation in genes relating to d4T transport and
      metabolism, as well as genetic variation in the thymidine synthesis pathway,
      could influence occurrence of d4T-related toxicity. METHODS: We examined this
      hypothesis in a cohort of HIV-positive South African adults exposed to d4T,
      including 143 cases with SN and 120 controls without SN. Ten SNPs in four genes
      associated with stavudine transport, and 16 SNPs in seven genes of the thymidine
      synthesis / phosphorylation pathway were genotyped using Agena mass spectrometry
      methods. Associations between sensory neuropathy and genetic variants were
      evaluated using PLINK by univariate and multivariable analyses. RESULTS: Age and
      height were significantly associated with SN occurrence. Using logistic
      regression with age and height as covariates, and uncorrected empirical p-values,
      genetic variation in SLC28A1, SAMHD1, MTHFR and RRM2B was associated with SN in
      South Africans using d4T. CONCLUSION: Variation in genes relating to d4T
      transport and metabolism, as well as genetic variation in the thymidine synthesis
      pathway may influence occurrence of d4T-related SN. These data contribute to the
      characterisation of African pharmacogenetic variation and its role in adverse
      response to antiretroviral therapy.

PMID- 30273370
TI  - Deciphering moral intuition: How agents, deeds, and consequences influence moral
      judgment.
AB  - Moral evaluations occur quickly following heuristic-like intuitive processes
      without effortful deliberation. There are several competing explanations for
      this. The ADC-model predicts that moral judgment consists in concurrent
      evaluations of three different intuitive components: the character of a person
      (Agent-component, A); their actions (Deed-component, D); and the consequences
      brought about in the situation (Consequences-component, C). Thereby, it explains
      the intuitive appeal of precepts from three dominant moral theories (virtue
      ethics, deontology, and consequentialism), and flexible yet stable nature of
      moral judgment. Insistence on single-component explanations has led to many
      centuries of debate as to which moral precepts and theories best describe (or
      should guide) moral evaluation. This study consists of two large-scale
      experiments and provides a first empirical investigation of predictions yielded
      by the ADC model. We use vignettes describing different moral situations in which
      all components of the model are varied simultaneously. Experiment 1 (within
      subject design) shows that positive descriptions of the A-, D-, and C-components
      of moral intuition lead to more positive moral judgments in a situation with low
      stakes. Also, interaction effects between the components were discovered.
      Experiment 2 further investigates these results in a between-subject design. We
      found that the effects of the A-, D-, and C-components vary in strength in a high
      stakes situation. Moreover, sex, age, education, and social status had no
      effects. However, preferences for precepts in certain moral theories (PPIMT)
      partially moderated the effects of the A- and C-component. Future research on
      moral intuitions should consider the simultaneous three-component constitution of
      moral judgment.

PMID- 30273372
TI  - Simulation and experimental study on control strategy of zero-speed fin
      stabilizer based on disturbance and compensation.
AB  - Zero-speed fin stabilizer is applied to reduce the roll motion of ships at zero
      speed. This paper aims to explore the control strategy of zero-speed fin
      stabilizer through a composite method of theoretical analysis, simulations and
      tank tests. The hydrodynamic force model is established using analytical approach
      and a simplified model is obtained by fitting the CFD simulation data. The
      control strategy of zero-speed fin stabilizer is obtained based on disturbance
      and compensation by analyzing the phase matching relationship between the wave
      disturbance, the roll motion of the ship, the movement of the fin and the fin
      induced hydrodynamic force. Simulations and water tank tests are performed to
      verify the effectiveness and feasibility of the obtained control strategies. The
      results of simulations and tank tests show that the obtained control strategies
      of zero-speed fin stabilizer based on disturbance and compensation are effective
      and practical. The proposed method provides theoretical and experimental support
      for engineering application, and can also be a reference for the controller
      design of zero-speed fin stabilizers.

PMID- 30273371
TI  - The impact of BMI on clinical progress, response to treatment, and disease course
      in patients with differentiated thyroid cancer.
AB  - INTRODUCTION: Obesity is a serious health problem worldwide, particularly in
      developed countries. It is a risk factor for many diseases, including thyroid
      cancer. The relationship between obesity and prognostic factors of thyroid cancer
      is unclear. AIMS: We sought to ascertain the relationship between body mass index
      (BMI) and clinicopathological features increasing the risk of poor clinical
      course, treatment response, and clinical outcome in patients with differentiated
      thyroid cancer (DTC). SUBJECTS & METHODS: The study included 1181 patients with
      DTC (88% women and 12% men) treated at a single center from 2000 to 2016. BMI
      before surgery and aggressive clinicopathological features, according to the
      American Thyroid Initial Risk stratification system, were analyzed. The
      relationship between BMI and initial risk, treatment response, and final status
      of the disease was evaluated, incorporating the revised 2015 American Thyroid
      Association guidelines and the 8th edition of the American Joint Committee on
      Cancer/Tumor-Node-Metastasis (AJCC/TNM) staging system. Patients were stratified
      according to the World Health Organization classification of BMI. Statistical
      analysis was performed using univariate and multivariate logistic regression
      analysis. RESULTS: Median follow-up was 7.7 years (1-16 years). There were no
      significant associations between BMI and extrathyroidal extension (microscopic
      and gross), cervical lymph node metastasis, or distant metastasis in univariate
      and multivariate analyses. BMI did not affect initial risk, treatment response or
      disease outcome. Obesity was more prevalent in men (p = 0.035) and in patients
      >=55 years old (p = 0.001). There was no statistically significant relationship
      between BMI and more advanced TNM stage in patients <=55 years old (stage I vs.
      stage II) (p = 0.266) or in patients >55 years old (stage I-II vs. III-IV) (p =
      0.877). CONCLUSIONS: Obesity is not associated with more aggressive
      clinicopathological features of thyroid cancer. Obesity is not a risk factor for
      progression to more advanced stages of disease, nor is it a prognostic factor for
      poorer treatment response and clinical outcome.

PMID- 30273373
TI  - Hematological responses to iron-folate supplementation and its determinants in
      pregnant women attending antenatal cares in Mekelle City, Ethiopia.
AB  - OBJECTIVE: To characterize anemia and evaluate hematological responses to
      universal iron-folic acid (IFA) supplementation in Ethiopian pregnant women.
      METHOD: A hospital- based prospective follow up study was done between December
      2016 and June 2017. Hematological profiles were measured in pregnant women before
      and after a minimum of one-month IFA supplementation. Mean values and abnormal
      proportions of hematological profiles were compared before and after
      supplementation using paired t-test and McNemar test, respectively. Univariate
      and multivariate analysis were used to analyze the association between
      independent variables and poor treatment responses. RESULT: Lack of adequate
      hemoglobin response was found in 48.5%(95/196) of the participants. Prevalence of
      anemia and low hematocrit value were decreased significantly after IFA
      supplementation (p = 0.002, and p = 0.001, respectively). Normocytic hypochromic
      anemia was the commonest form of anemia found in this study followed by
      normocytic normochromic anemia. There was no statistically significant
      association between poor hemoglobin responses and all studied factors such as
      educational level, household size, parity, recent illness, stage of pregnancy,
      coffee consumption, and duration of iron treatment. CONCLUSION: Our study
      revealed poor hemoglobin responses in nearly half of the study participants and a
      high proportion of anemias morphologically atypical of iron deficiency anemia.
      There is a need to consider anemia attributable to etiologies other than an iron
      deficiency in anemia intervention programs.

PMID- 30273374
TI  - Isolated perfused working hearts provide valuable additional information during
      phenotypic assessment of the diabetic mouse heart.
AB  - Although murine models for studying the development of cardiac dysfunction in
      diabetes mellitus are well established, their reported cardiac phenotypes vary.
      These reported divergences may, in addition to the severity of different models,
      also be linked to the methods used for cardiac functional assessment. In the
      present study, we examined the functional changes using conventional
      transthoracic echocardiography (in vivo) and isolated heart perfusion techniques
      (ex vivo), in hearts from two mouse models; one with an overt type 2 diabetes
      (the db/db mouse) and one with a prediabetic state, where obesity was induced by
      a high-fat diet (HFD). Analysis of left ventricular function in the isolated
      working hearts from HFD-fed mice, suggested that these hearts develop diastolic
      dysfunction with preserved systolic function. Accordingly, in vivo examination
      demonstrated maintained systolic function, but we did not find parameters of
      diastolic function to be altered. In db/db mice, ex vivo working hearts showed
      both diastolic and systolic dysfunction. Although in vivo functional assessment
      revealed signs of diastolic dysfunction, the hearts did not display reduced
      systolic function. The contrasting results between ex vivo and in vivo function
      could be due to systemic changes that may sustain in vivo function, or a lack of
      sensitivity using conventional transthoracic echocardiography. Thus, this study
      demonstrates that the isolated perfused working heart preparation provides unique
      additional information related to the development of cardiomyopathy, which might
      otherwise go unnoticed when only using conventional echocardiographic assessment.

PMID- 30273375
TI  - Decline in AmpC beta-lactamase-producing Escherichia coli in a Dutch teaching
      hospital (2013-2016).
AB  - OBJECTIVE: The objective of this study is to determine the prevalence of rectal
      carriage of plasmid- and chromosome-encoded AmpC beta-lactamase-producing
      Escherichia coli and Klebsiella spp. in patients in a Dutch teaching hospital
      between 2013 and 2016. METHODS: Between 2013 and 2016, hospital-wide yearly
      prevalence surveys were performed to determine the prevalence of AmpC beta
      lactamase-producing E. coli and Klebsiella spp. rectal carriage. Rectal swabs
      were taken and cultured using an enrichment broth and selective agar plates. All
      E. coli and Klebsiella spp. isolates were screened for production of AmpC beta
      lactamase using phenotypic confirmation tests and for the presence of plasmid
      encoded AmpC (pAmpC) genes. E. coli isolates were screened for chromosome-encoded
      AmpC (cAmpC) promoter/attenuator alterations. RESULTS: Fifty (2.4%) of 2,126
      evaluable patients were identified as rectal carrier of AmpC beta-lactamase
      producing E. coli. No carriage of AmpC beta-lactamase producing Klebsiella spp.
      was found. Nineteen (0.9%) patients harboured isolates with pAmpC genes and 30
      (1,4%) patients harboured isolates with cAmpC promoter/attenuator alterations
      associated with AmpC beta-lactamase overproduction. For one isolate, no pAmpC
      genes or cAmpC promotor/attenuator alterations could be identified. During the
      study period, a statistically significant decline in the prevalence of rectal
      carriage with E. coli with cAmpC promotor/attenuator alterations was found (p =
      0.012). The prevalence of pAmpC remained stable over the years. CONCLUSIONS: The
      prevalence of rectal carriage of AmpC-producing E. coli and Klebsiella spp. in
      patients in Dutch hospitals is low and a declining trend was observed for E. coli
      with cAmpC promotor/attenuator alterations.

PMID- 30273378
TI  - On-demand route discovery in a unicast manner.
AB  - While having high bandwidth-efficiency, the ad-hoc on-demand distance vector
      (AODV) routing protocol suffers from high signaling overhead due to route request
      (RREQ) messages flooding, especially when the node density and the number of
      connections are increased. In order to resolve this broadcast storm problem of
      the AODV in a high node density mobile ad-hoc network, we propose a geographical
      on-demand route discovery scheme. Assuming a known location of the destination,
      the RREQ of the proposed routing protocol is propagated in a unicast manner by
      employing a novel parsing mechanism for possible duplicate RREQs. The routing
      overhead of the proposed routing protocol is greatly robust to the node density
      change. We derive the node density required for the proposed routing protocol to
      keep the same connectivity as the AODV under the circumstance where the nodes are
      uniformly distributed. In addition, we present an imaginary destination
      consideration method to incorporate the uncertainty of the destination's location
      due to mobility. Computer simulations show that the proposed scheme enables the
      RREQ propagation to cover 95% of the one-hop communication area centered at the
      originally known location of the destination without sacrificing the unicast
      feature.

PMID- 30273377
TI  - Different culture media modulate growth, heterogeneity, and senescence in human
      mammary epithelial cell cultures.
AB  - The ability to culture normal human mammary epithelial cells (HMEC) greatly
      facilitates experiments that seek to understand both normal mammary cell biology
      and the many differences between normal and abnormal human mammary epithelia. To
      maximize in vivo relevance, the primary cell culture conditions should maintain
      cells in states that resemble in vivo as much as possible. Towards this goal, we
      compared the properties of HMEC strains from two different reduction mammoplasty
      tissues that were grown in parallel using different media and culture conditions.
      Epithelial organoids were initiated into three different media: two commonly used
      serum-free-media, MCDB 170-type (e.g. MEGM) and WIT-P, and a low stress media,
      M87A. Growth, lineage heterogeneity, p16 protein expression, and population
      doublings to senescence were measured for each culture condition. MCDB 170 caused
      rapid senescence and loss of heterogeneity within 2 to 3 passages, but some
      cultures went through the 1 to 2 month process of selection to generate clonal
      finite post-selection post-stasis cells. WIT-P caused impressive expansion of
      luminal cells in 2nd passage followed by their near complete disappearance by
      passage 4 and senescence shortly thereafter. M87A supported as much as twice the
      number of population doublings compared to either serum-free medium, and luminal
      and myoepithelial cells were present for as many as 8 passages. Thus, of the
      three media compared, WIT-P and MCDB 170 imposed rapid senescence and loss of
      lineage heterogeneity, phenotypes consistent with cells maintained in high-stress
      conditions, while M87A supported cultures that maintained multiple lineages and
      robust growth for up to 60 population doublings. In conjunction with previous
      studies examining the molecular properties of cultures grown in these media, we
      conclude that M87A medium is most able to support long-term culture of multiple
      lineages similar to in vivo conditions, thereby facilitating investigations of
      normal HMEC biology relevant to the mammary gland in situ.

PMID- 30273376
TI  - MRI-guided intracerebral convection-enhanced injection of gliotoxins to induce
      focal demyelination in swine.
AB  - Demyelinating disorders such as multiple sclerosis (MS) or transverse myelitis
      are devastating neurological conditions with no effective cure. Prevention of
      myelin loss or restoration of myelin are key for successful therapy. To
      investigate the disease and develop cures animal models with good clinical
      relevance are essential. The goal of the current study was to establish a model
      of focal demyelination in the brain of domestic pig using MRI-guided gliotoxin
      delivery. The rationale for developing a new myelin disease model in the domestic
      pig was based on the fact that the brain in pigs is anatomically and
      histologically much more similar to that of humans compared to the rodent brain.
      For MRI-assisted gliotoxin injection, eight 30 kg pigs were subjected to
      treatment with lysolecithin (20, 30 mg/ml); or with ethidium bromide (0.0125,
      0.05, 0.2 mg/ml). Animals were placed in an MRI scanner for intraparenchymal
      targeting of gliotoxin into the corona radiata (250 MUl over 1h), with real-time
      monitoring of toxin distribution on T1 scans and monitoring of lesion evolution
      over seven days using both T1 and T2 scans. After the last MRI, animals were
      transcardially perfused and brains were processed for histological and
      immunofluorescent analysis. Gadolinium-enhanced T1 MRI during injection
      demonstrated biodistribution of the contrast (as a surrogate marker for toxin
      distribution) and its diffusion through the brain parenchyma. Lesion induction
      was confirmed on T2-weighted MRI and histopathology, thus enabling the
      establishment of optimal doses of gliotoxins. To conclude, MRI-guided focal
      demyelination in swine is accurate and provides real-time confirmation of
      gliotoxin, thus facilitating placement of focal lesions with high precision. This
      new model of focal demyelination can be used for further investigation and
      development of novel therapeutic approaches.

PMID- 30273379
TI  - Regulation of the NRF2 transcription factor by andrographolide and organic
      extracts from plant endophytes.
AB  - The transcription factor NF-E2 Related Factor-2 (NRF2) is an important drug
      target. Activation of NRF2 has chemopreventive effects in cancer and exerts
      beneficial effects in a number of diseases, including neurodegenerative diseases,
      inflammatory diseases, hepatosteatosis, obesity and insulin resistance. Hence,
      there have been great efforts to discover and characterize novel NRF2 activators.
      One reported NRF2 activator is the labdane diterpenoid andrographolide. In this
      study, we identified the mechanism through which andrographolide activates NRF2.
      We showed that andrographolide inhibits the function of KEAP1, a protein that
      together with CUL3 and RBX1 forms an E3 ubiquitin ligase that polyubiquitinates
      NRF2. Andrographolide partially inhibits the interaction of KEAP1 with CUL3 in a
      manner dependent on Cys151 in KEAP1. This suggests that andrographolide forms
      Michael acceptor dependent adducts with Cys151 in KEAP1 in vivo, leading to
      inhibition of NRF2 ubiquitination and consequently accumulation of the
      transcription factor. Interestingly, we also showed that at higher concentrations
      andrographolide increases NRF2 protein expression in a Cys151 independent, but
      likely KEAP1 dependent manner, possibly through modification of other Cys
      residues in KEAP1. In this study we also screened secondary metabolites produced
      by endophytes isolated from non-flowering plants for NRF2-inducing properties.
      One of the extracts, ORX 41, increased both NRF2 protein expression and
      transcriptional activity markedly. These results suggest that endophytes isolated
      from non-flowering or other plants may be a good source of novel NRF2 inducing
      compounds.

PMID- 30273380
TI  - Meta-analysis of the association between the inflammatory potential of diet and
      urologic cancer risk.
AB  - BACKGROUND: The inflammatory potential of diet has been shown to have an
      association with the risk of several cancer types, but the evidence is
      inconsistent regarding the related risk of urologic cancer (UC). Therefore, we
      conducted the present meta-analysis to investigate the association between the
      inflammatory potential of diet and UC. METHODS: PubMed, Embase and Web of Science
      were searched up to July 31, 2018. Two reviewers independently selected the
      studies and extracted the data. The pooled risk ratio (RR) and its 95% confidence
      interval (CI) were calculated using the Stata12.0 software package. RESULTS: Nine
      case-control studies and three cohort studies including 83,197 subjects met the
      inclusion criteria. The overall meta-analysis results showed that individuals
      with the highest category of DII (dietary inflammatory index) were associated
      with an increased risk of prostate cancer (RR = 1.62, 95% CI: 1.30-2.02);
      subgroup analysis showed consistent results. For kidney and bladder cancer,
      significant positive associations were found in individuals with the highest
      category of DII score; however, no significant association was found between DII
      and the risk of urothelial cell carcinoma (UCC). CONCLUSION: Available data
      suggest that more pro-inflammatory diets are associated with an increased risk of
      prostate cancer, kidney cancer and bladder cancer. However, further well designed
      large-scaled cohort studies are warranted to provide more conclusive evidence.

PMID- 30273381
TI  - Knowledge of preconception care among healthcare providers working in public
      health institutions in Hawassa, Ethiopia.
AB  - BACKGROUND: Preconception care (PCC) is an evidence-based health promotion
      intervention to prevent adverse pregnancy outcomes. Nevertheless, it is one of
      the missing elements within the continuum of maternal and child healthcare.
      Despite the WHO's recommendation, most of the developing countries have not yet
      started implementing preconception care. OBJECTIVE: To determine the knowledge
      level of healthcare providers about PCCand to identify predictors of effective
      knowledge of preconception care. METHOD: This is a cross-sectional study
      conducted among 634 healthcare providers (HCP) working in public health
      institutions of Hawassa. A pilot-tested and validated self-administered survey
      tool was used to collect data from individual healthcare providers who were
      selected randomly using a multistage sampling technique. The data entry and
      analysis were conducted using SPSS version 20 software. Frequency, proportions,
      means and standard deviations were used to describe the data. Bivariate and
      multivariate logistic regression models were implemented to determine the
      predictors of HCP's PCC knowledge. RESULTS: Only a few (31%) of the healthcare
      providers demonstrated a good level of knowledge on preconception care. The odds
      of having good PCC knowledge was high among HCPs working in hospitals (AOR = 1.8,
      95% C.I. 1.3-2.6), HCPs using their smart phone to access clinical resources (AOR
      = 1.4, 95% C.I. 1.1-2.0), among those HCPs ever have read PCC guideline prepared
      by organization outside of Ethiopia (AOR = 1.9, 95% C.I. 1.4-2.7), among those
      who claimed practicing PCC (AOR = 3.4, 95% C.I. 2.0-5.9), and among those who
      earn salary of >= 146.0 $(AOR = 1.5, 95% C.I. 1.1-2.1). CONCLUSION: There is an
      unacceptably low level of knowledge about PCC among most of the healthcare
      providers in public health facilities in Ethiopia. The predictors identified in
      this study can be used to enhance the knowledge of healthcare providers about
      preconception care.

PMID- 30273382
TI  - Diagnostic value of STAF score in combination with D-dimer in cardioembolism.
AB  - The aim of this study was to evaluate the diagnostic value of the Score for the
      Targeting of Atrial Fibrillation (STAF) in combination with the serum D-dimer
      (DD) levels in cardioembolism(CE).This study was a retrospective case-onlystudy,
      consecutively including patients with acute ischemic stroke. All patients were
      evaluated following the STAF scoring criteria and were classified according to
      the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) etiology classification
      criteria. A total of 317 patients were enrolled, including 37 CE cases (11.67%).
      STAF >=5 showed a sensitivity of 89% and a specificity of 91% for the diagnosis
      of CE, whereas DD >791.30 ng/mL had a sensitivity of 58% and a specificity of
      78%. When the STAF was used in combination with the DD level, the sensitivity was
      95%, and the specificity was 100%.STAF score is an excellent tool for the
      diagnosis of CE when combined with DD, and can facilitate the etiological
      classification of acute ischemic stroke.

PMID- 30273383
TI  - A stochastic model of myeloid cell lineages in hematopoiesis and pathway
      mutations in acute myeloid leukemia.
AB  - A model for hematopoiesis is presented that explicitly includes the erythrocyte,
      granulocyte, and thrombocyte lineages and their common precursors. A small number
      of stem cells proliferate and differentiate through different compartments to
      produce the vast number of blood cells needed every day. Growth factors regulate
      the proliferation of cells dependent on the current demand. We provide a steady
      state analysis of the model and rough parameter estimates. Furthermore, we extend
      the model to include mutations that alter the replicative capacity of cells and
      introduce differentiation blocks. With these mutations the model develops signs
      of acute myeloid leukemia.

PMID- 30273384
TI  - Laplacian mixture modeling for network analysis and unsupervised learning on
      graphs.
AB  - Laplacian mixture models identify overlapping regions of influence in unlabeled
      graph and network data in a scalable and computationally efficient way, yielding
      useful low-dimensional representations. By combining Laplacian eigenspace and
      finite mixture modeling methods, they provide probabilistic or fuzzy
      dimensionality reductions or domain decompositions for a variety of input data
      types, including mixture distributions, feature vectors, and graphs or networks.
      Provable optimal recovery using the algorithm is analytically shown for a
      nontrivial class of cluster graphs. Heuristic approximations for scalable high
      performance implementations are described and empirically tested. Connections to
      PageRank and community detection in network analysis demonstrate the wide
      applicability of this approach. The origins of fuzzy spectral methods, beginning
      with generalized heat or diffusion equations in physics, are reviewed and
      summarized. Comparisons to other dimensionality reduction and clustering methods
      for challenging unsupervised machine learning problems are also discussed.

PMID- 30273385
TI  - Trust-based altruism facing new contexts: The Vyegwa-Gika pygmies from Burundi.
AB  - The community of Pygmies settled in Vyegwa-Gika provides an exceptional case
      study to test the role of trust in the evolution of altruism. The Vyegwa-Gika
      Pygmies were forced to migrate from rainforests to the savanna, changing quickly
      their environment, culture, and socio-economic situation. Despite the high level
      of poverty they suffer in this new settlement, we found evidence of strong
      altruistic attitudes toward trustees when playing an economic game. In addition,
      Vyegwa-Gika Pygmies keep small personal trust networks despite the fact they
      share frequent social interactions within the community. These results indicate
      the great effectiveness of personal trust in fostering altruism, even if the
      circumstances make it difficult to establish such kind of affective bonds. A
      theory of the evolution of altruism should therefore also account for the
      evolution of psychology of trust, as a key element in the process.

PMID- 30273388
TI  - The eCura system as a novel indicator for the necessity of salvage surgery after
      non-curative ESD for gastric cancer: A case-control study.
AB  - Endoscopic submucosal dissection (ESD) for early gastric cancer does not always
      lead to complete cancer resection. The aim of this study was to determine
      indicators for cancer residue (CR) status in cases of non-curative ESD. We
      analyzed 47 cases of non-curative ESD followed by salvage surgery and collected
      data regarding the rates of CR, which included both local CR and lymph node
      metastasis (LNM). To elucidate the risk factors for CR status, we compared the CR
      positive and the CR negative groups among surgical specimens according to the
      following variables obtained from ESD findings: tumor location, tumor size, depth
      of invasion, lympho-vascular invasion, histological margin, and histological
      diagnosis. The eCura system, which is an LNM risk scoring system, was also
      applied and scores were calculated in each case as follows: 3 points for
      lymphatic invasion and 1 point each for tumor size >30 mm, positive vertical
      margin, venous invasion, and submucosal invasion >=500 MUm. There were 9 (19%) CR
      positive cases, which included 6 cases of local CR and 4 cases of LNM; no cancer
      was detected in over 80% of the patients. The eCura scoring system was the only
      significant factor for CR status: the higher the eCura score, the greater the CR
      positivity (p = 0.0128). In particular, all patients in the low-risk group (score
      = 0-1 point) had no CR. Although no cancer recurrence was observed during a
      median follow-up of 4 years, 2 patients died of pneumonia. In conclusion, the
      eCura system might make it possible to select appropriate cases for salvage
      surgery.

PMID- 30273389
TI  - Correction: Disrupted dispersal and its genetic consequences: Comparing protected
      and threatened baboon populations (Papio papio) in West Africa.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0194189.].

PMID- 30273387
TI  - First evidence of Halomicronema metazoicum (Cyanobacteria) free-living on
      Posidonia oceanica leaves.
AB  - Cyanobacteria contribute to the ecology of various marine environments, also for
      their symbioses, since some of them are common hosts of sponges and ascidians.
      They are also emerging as an important source of novel bioactive secondary
      metabolites in pharmacological (as anticancer drugs) and biotechnological
      applications. In the present work we isolated a cyanobacteria in a free-living
      state from leaves of the seagrass Posidonia oceanica leaves. This newly collected
      strain was then cultivated under two laboratory conditions, and then
      characterized by combining morphological observation and molecular studies based
      on 16S rRNA gene sequences analysis. The strain showed 99% pairwise sequence
      identity with Halomicronema metazoicum ITAC101, never isolated before as a free
      living organisms, but firstly described as an endosymbiont of the Mediterranean
      marine spongae Petrosia ficiformis, under the form of a filamentous strain.
      Further studies will investigate the actual role of this cyanobacterium in the
      leaf stratum of P. oceanica leaves, given its demonstrated ability to influence
      the vitality and the life cycle of other organisms. In fact, its newly
      demonstrated free-living stage, described in this study, indicate that Phormidium
      like cyanobacteria could play important roles in the ecology of benthic and
      planktonic communities.

PMID- 30273386
TI  - Lack of vitamin D signalling per se does not aggravate cardiac functional
      impairment induced by myocardial infarction in mice.
AB  - Epidemiological studies have linked vitamin D deficiency to an increased
      incidence of myocardial infarction and support a role for vitamin D signalling in
      the pathophysiology of myocardial infarction. Vitamin D deficiency results in the
      development of secondary hyperparathyroidism, however, the role of secondary
      hyperparathyroidism in the pathophysiology of myocardial infarction is not known.
      Here, we aimed to explore further the secondary hyperparathyroidism independent
      role of vitamin D signalling in the pathophysiology of myocardial infarction by
      inducing experimental myocardial infarction in 3-month-old, male, wild-type mice
      and in mice lacking a functioning vitamin D receptor. In order to prevent
      secondary hyperparathyroidism in vitamin D receptor mutant mice, all mice were
      maintained on a rescue diet enriched with calcium, phosphorus, and lactose.
      Surprisingly, survival rate, cardiac function as measured by echocardiography and
      intra-cardiac catheterisation and cardiomyocyte size were indistinguishable
      between normocalcaemic vitamin D receptor mutant mice and wild-type controls, 2
      and 8 weeks post-myocardial infarction. In addition, the myocardial infarction
      induced inflammatory response was similar in vitamin D receptor mutants and wild
      type mice, as evidenced by a comparable upregulation in cardiac interleukin-1
      beta and tumor-necrosis-factor-alpha mRNA abundance and similar elevations in
      circulating interleukin-1-beta and tumor-necrosis-factor-alpha. Our data suggest
      that the lack of vitamin D signalling in normocalcaemic vitamin D receptor
      mutants has no major detrimental effect on cardiac function and outcome post
      myocardial infarction. Our study may have important clinical implications because
      it suggests that the secondary hyperparathyroidism induced by vitamin D
      deficiency, rather than the lack of vitamin D signalling per se, may negatively
      impact cardiac function post-myocardial infarction.

PMID- 30273391
TI  - Light control of G protein signaling pathways by a novel photopigment.
AB  - Channelopsins and photo-regulated ion channels make it possible to use light to
      control electrical activity of cells. This powerful approach has lead to a
      veritable explosion of applications, though it is limited to changing membrane
      voltage of the target cells. An enormous potential could be tapped if similar
      opto-genetic techniques could be extended to the control of chemical signaling
      pathways. Photopigments from invertebrate photoreceptors are an obvious choice-as
      they do not bleach upon illumination -however, their functional expression has
      been problematic. We exploited an unusual opsin, pScop2, recently identified in
      ciliary photoreceptors of scallop. Phylogenetically, it is closer to vertebrate
      opsins, and offers the advantage of being a bi-stable photopigment. We inserted
      its coding sequence and a fluorescent protein reporter into plasmid vectors and
      demonstrated heterologous expression in various mammalian cell lines. HEK 293
      cells were selected as a heterologous system for functional analysis, because
      wild type cells displayed the largest currents in response to the G-protein
      activator, GTP-gamma-S. A line of HEK cells stably transfected with pScop2 was
      generated; after reconstitution of the photopigment with retinal, light responses
      were obtained in some cells, albeit of modest amplitude. In native photoreceptors
      pScop2 couples to Go; HEK cells express poorly this G-protein, but have a
      prominent Gq/PLC pathway linked to internal Ca mobilization. To enhance pScop2
      competence to tap into this pathway, we swapped its third intracellular loop
      important to confer specificity of interaction between 7TMDRs and G-proteins-with
      that of a Gq-linked opsin which we cloned from microvillar photoreceptors present
      in the same retina. The chimeric construct was evaluated by a Ca fluorescence
      assay, and was shown to mediate a robust mobilization of internal calcium in
      response to illumination. The results project pScop2 as a potentially powerful
      optogenetic tool to control signaling pathways.

PMID- 30273392
TI  - Transcriptome analyses of Atlantic salmon muscle genes induced by a DNA vaccine
      against salmonid alphavirus, the causative agent of salmon pancreas disease (PD).
AB  - Salmonid alphavirus (SAV) is the causative agent of pancreas disease (PD) in
      farmed Atlantic salmon. A previous study showed that vaccination of pre-smolt
      salmon with a plasmid encoding the structural polypeptide of SAV gave protection
      against infection and development of PD accompanied by production of antibodies
      against the virus. In the present work we analyzed transcript responses in the
      muscle to vaccination with this plasmid (here named pSAV). The purpose was to
      shed light on how pSAV might initiate adaptive immune responses in the fish. The
      work was based on microarray and reverse transcription quantitative PCR analyses
      of muscle at the injection site 7 days after vaccination. The results showed that
      pSAV and pcDNA3.3 had similar abilities to up-regulate type I IFN stimulated
      genes. In contrast, pSAV caused higher up-regulation of IFNgamma and several
      IFNgamma inducible genes. Compared to pcDNA3.3, pSAV also gave larger increase in
      transcripts of marker genes for B-cells, T-cells and antigen presenting cells
      (APCs), which suggest attraction and role of these cells in the adaptive immune
      responses elicited by pSAV. Moreover, pSAV caused a stronger up-regulation of the
      chemokine CXCL10 and the proinflammatory cytokines IL-1beta and TNFalpha, which
      may explain attraction of lymphocytes and APCs. The present work shows that the
      expression profile of genes resulting from vaccination with pSAV is different
      from the expression profiles obtained previously by vaccination of salmonids with
      DNA vaccines against infectious salmon anemia virus and infectious hematopoietic
      necrosis virus.

PMID- 30273390
TI  - Age-specific global epidemiology of hydrocephalus: Systematic review, metanalysis
      and global birth surveillance.
AB  - BACKGROUND: Hydrocephalus is a debilitating disorder, affecting all age groups.
      Evaluation of its global epidemiology is required for healthcare planning and
      resource allocation. OBJECTIVES: To define age-specific global prevalence and
      incidence of hydrocephalus. METHODS: Population-based studies reporting
      prevalence of hydrocephalus were identified (MEDLINE, EMBASE, Cochrane, and
      Google Scholar (1985-2017)). Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses guidelines were followed. Two authors reviewed abstracts, full text
      articles and abstracted data. Metanalysis and meta-regressions were used to
      assess associations between key variables. Heterogeneity and publication bias
      were assessed. Main outcome of interest was hydrocephalus prevalence among
      pediatric (<= 18 years), adults (19-64 years), and elderly (>= 65) patients.
      Annual hydrocephalus incidence stratified by country income level and folate
      fortification requirements were obtained (2003-2014) from the International
      Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). RESULTS: Of
      2,460 abstracts, 52 met review eligibility criteria (aggregate population
      171,558,651). Mean hydrocephalus prevalence was 85/100,000 [95% CI 62, 116]. The
      prevalence was 88/100,000 [95% CI 72, 107] in pediatrics; 11/100,000 [95% CI 5,
      25] in adults; and 175/100,000 [95% CI 67, 458] in the elderly. The ICBDSR-based
      incidence of hydrocephalus diagnosed at birth remained stable over 11 years:
      81/100,000 [95% CI 69, 96]. A significantly lower incidence was identified in
      high-income countries. CONCLUSION: This systematic review established age
      specific global hydrocephalus prevalence. While high-income countries had a lower
      hydrocephalus incidence according to the ICBDSR registry, folate fortification
      status was not associated with incidence. Our findings may inform future
      healthcare resource allocation and study.

PMID- 30273393
TI  - Use of data-mining to support real-world cost analyses: An example using HER2
      positive breast cancer in Iran.
AB  - INTRODUCTION: Patient registries play an important role in obtaining real-world
      evidence of the cost-effectiveness of treatments. However, their implementation
      is costly and sometimes infeasible in many middle-income countries (MICs). We
      explored the combination of data-mining and a large claims database to estimate
      the direct healthcare costs of HER2-positive breast cancer (BC) treatment in Iran
      and the fraction of total costs from trastuzumab use. METHOD: We performed a
      retrospective analysis of claims data from the Iran Social Security Organization,
      a health insurer which covers approximately 50%(~40 million) of the Iranian
      population, in the period of 21/03/2011-20/03/2014. A data-mining algorithm using
      R software and validated using patient dossiers in the Cancer Research Center
      identified 1295 patients and divided them into the three main HER2-positive
      breast cancer stages (early, loco-regional and advanced). A payer perspective was
      used to calculate the absolute and relative direct costs of healthcare services
      associated with the treatment of HER2-positive breast cancer in the public and
      private healthcare systems. RESULTS: The number of women totaled 802 (early), 125
      (loco-regional) and 218 (advanced). The mean age[SD] was 45[10], 46[10] and
      48[10] years, respectively, while mean follow-up in all stages was approximately
      one year. Average costs of direct healthcare care in early, loco-regional and
      advanced stages were ?11,796 (95%CI: ?9,356-?12,498), ?8,253 (95%CI: ?6,843
      ?10,002), and ?17,742 (95%CI: ?15,720-?19,505), respectively. Trastuzumab
      accounted for the largest share of total costs in all three stages (range: 53
      76%). CONCLUSION: Wherever comprehensive patient registries are infeasible or
      costly, real-world costs can be estimated through claims databases and data
      mining strategies. Using this method, real-world costs have been estimated in
      Iran. The stage-specific cost estimates derived from this study can be used to
      perform real-world cost-effectiveness analyses of therapies for HER2-positive BC
      and support healthcare financing decisions.

PMID- 30273394
TI  - Klebsiella pneumoniae infection of murine neutrophils impairs their efferocytic
      clearance by modulating cell death machinery.
AB  - Neutrophils are the first infiltrating cell type essential for combating
      pneumoseptic infections by bacterial pathogens including Klebsiella pneumoniae
      (KPn). Following an infection or injury, removal of apoptotic infiltrates via a
      highly regulated process called efferocytosis is required for restoration of
      homeostasis, but little is known regarding the effect of bacterial infection on
      this process. Here we demonstrate that KPn infection impedes the efferocytic
      uptake of neutrophils in-vitro and in-vivo in lungs by macrophages. This impaired
      efferocytosis of infected neutrophils coincides with drastic reduction in the
      neutrophil surface exposure of apoptosis signature phospholipid phosphatidyserine
      (PS); and increased activity of phospholipid transporter flippases, which
      maintain PS in the inner leaflet of plasma membrane. Concomitantly,
      pharmacological inhibition of flippase activity enhanced PS externalization and
      restored the efferocytosis of KPn infected neutrophils. We further show that KPn
      infection interferes with apoptosis activation and instead activates non
      apoptotic programmed cell death via activation of necroptosis machinery in
      neutrophils. Accordingly, pharmacological inhibition of necroptosis by RIPK1 and
      RIPK3 inhibitors restored the efferocytic uptake of KPn infected neutrophils in
      vitro. Importantly, treatment of KPn infected mice with necroptosis inhibitor
      improved the disease outcome in-vivo in preclinical mouse model of KPn pneumonia.
      To our knowledge, this is the first report of neutrophil efferocytosis impairment
      by KPn via modulation of cell death pathway, which may provide novel targets for
      therapeutic intervention of this infection.

PMID- 30273395
TI  - Loss of murine Paneth cell function alters the immature intestinal microbiome and
      mimics changes seen in neonatal necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal
      morbidity and mortality in premature infants. Human and animal studies suggest a
      role for Paneth cells in NEC pathogenesis. Paneth cells play critical roles in
      host-microbial interactions and epithelial homeostasis. The ramifications of
      eliminating Paneth cell function on the immature host-microbial axis remains
      incomplete. Paneth cell function was depleted in the immature murine intestine
      using chemical and genetic models, which resulted in intestinal injury consistent
      with NEC. Paneth cell depletion was confirmed using histology, electron
      microscopy, flow cytometry, and real time RT-PCR. Cecal samples were analyzed at
      various time points to determine the effects of Paneth cell depletion with and
      without Klebsiella gavage on the microbiome. Deficient Paneth cell function
      induced significant compositional changes in the cecal microbiome with a
      significant increase in Enterobacteriacae species. Further, the bloom of
      Enterobacteriaceae species that occurs is phenotypically similar to what is seen
      in human NEC. This further strengthens our understanding of the importance of
      Paneth cells to intestinal homeostasis in the immature intestine.

PMID- 30273396
TI  - Fibroblast growth factor 2 is necessary for the antidepressant effects of
      fluoxetine.
AB  - Previous research has shown that fibroblast growth factor 2 protein (FGF2) can
      act as an anxiolytic and anti-depressive agent in rodents. Levels of hippocampal
      FGF2 and FGF2 receptors are decreased in post-mortem brains of individuals with
      mood disorders. No changes in FGF2 were noted in the post-mortem brains of
      individuals with mood disorders that were successfully treated with anti
      depressant medication prior to death. Mutations in the FGF2 gene in humans have
      been shown to predict non-responsiveness to the therapeutic effects of selective
      serotonin reuptake inhibitors (SSRIs). These findings suggest that FGF2 may
      potentially be a target of and/or required for the therapeutic effects of
      antidepressant medications. To test this, we employed a rodent model of
      depressive behaviour, chronic variable stress (CVS) in conjunction with
      antidepressant treatment (fluoxetine) in wild-type (WT) and FGF2 knockout mice
      (FGF2KO) and examined depressive and anxiety behaviors. Results showed that
      fluoxetine reversed the effects of CVS on depressive and anxiety behaviours in
      wild-type mice only, suggesting that the FGF2 gene is indeed necessary for the
      therapeutic effects of fluoxetine. Interestingly, CVS decreased hippocampal FGF2
      levels and fluoxetine partially reversed this effect. Because FGF2 has been
      previously shown to modify HPA activity through hippocampal glucocorticoid
      receptors (GR), we examined levels of glucocorticoid receptors and found a
      decrease in GR in response to CVS, with a further decrease in FGF2KO. No effect
      of fluoxetine on GR was observed in either WT or FGF2KO mice. This suggests that
      further changes in glucocorticoid receptors are not necessary for the anti
      depressant effects of fluoxetine in WT mice, although decreased glucocorticoid
      receptors in response to FGF2 deletion may preclude the therapeutic actions of
      fluoxetine in FGF2KO. Whether astroglia, astroglial functions, or HPA changes are
      the downstream target of FGF2-mediated changes induced by fluoxetine remains to
      be determined, however, the current study reaffirms the potential of FGF2 as a
      novel therapeutic target in the treatment of depression and anxiety disorders.

PMID- 30273397
TI  - Ziziphus spina-christi leaf extract ameliorates schistosomiasis liver granuloma,
      fibrosis, and oxidative stress through downregulation of fibrinogenic signaling
      in mice.
AB  - Schistosomiasis is a widespread parasitic infection that affects humans, as well
      as wild and domestic animals. It ranks second after malaria, with a significant
      health and socio-economic impact in the developing countries. The objective of
      this study was to assess the anti-schistosomal impact of Ziziphus spina-christi
      leaf extract (ZLE) on Schistosoma mansoni-induced liver fibrosis in CD-1 Swiss
      male albino mice. S. mansoni infection was achieved by dipping of mouse tails in
      schistosomal cercariae. ZLE treatment was initiated at 46 days post-infection by
      administering a dose of the extract on a daily basis for 10 consecutive days. S.
      mansoni infection resulted in liver granuloma and fibrosis, with a drastic
      elevation in liver function factors, nitric oxide, and lipid peroxidation, which
      were associated with a reduction in glutathione content and substantial
      inhibition of antioxidant enzyme activities compared to those of the control.
      Induction of hepatic granuloma, oxidative stress, and fibrosis in the liver was
      controlled by ZLE administration, which also produced inhibition of matrix
      metalloproteinase-9, alpha-smooth muscle actin, transforming growth factor-beta,
      and tissue inhibitors of metalloproteinases expressions. In addition, the S.
      mansoni-infected group exhibited an increase in Bax and caspase-3 levels and a
      decrease in Bcl-2 level. However, treatment with ZLE mainly mitigated apoptosis
      in the liver. Thus, the findings of this study revealed that Ziziphus spina
      christi had anti-apoptotic, anti-fibrotic, antioxidant, and protective effects on
      S. mansoni-induced liver wounds. The benefits of Ziziphus spina-christi extract
      on S. mansoni were partly partially mediated by enhancing anti-fibrinogenic and
      nuclear factor erythroid 2-related factor 2 (Nrf2) pathways.

PMID- 30273398
TI  - Body mass index may predict the response to ipilimumab in metastatic melanoma: An
      observational multi-centre study.
AB  - INTRODUCTION: Immunotherapy is a well-established treatment option in patients
      with metastatic melanoma. However, biomarkers that can be used to predict a
      response in these patients have not yet been found, putting patients at risk of
      severe side effects. METHODS: In this retrospective analysis, we investigated the
      association between the body mass index and ipilimumab treatment response in
      patients with metastatic melanoma. Patients with metastatic melanoma who received
      a monotherapy of up to 4 doses of ipilimumab (3 mg/kg) every 3 weeks from 2011 to
      2014 in three major hospitals in Austria were included. Patients were classified
      into two groups: normal group (BMI<25) and overweight group (BMI>=25). RESULTS:
      40 patients had a normal BMI, and 36 had a BMI above normal. Patients with a BMI
      that was above normal showed significantly higher response rates (p = 0.024,
      chi2), and lower likelihood of brain metastases (p = 0.012, chi2). No differences
      were found between both groups with respect to gender (p = 0.324, chi2), T-stage
      (p = 0.197, chi2), or the occurrence of side effects (p = 0.646, chi2). Patients
      with a BMI above normal showed a trend towards longer overall survival (p =
      0.056, Log-Rank), but no difference was found regarding progression-free survival
      (p = 0.924, Log-Rank). CONCLUSIONS: The BMI correlated with the response to
      ipilimumab treatment in a cohort of metastatic melanoma patients.

PMID- 30273399
TI  - Pathological alleles of MPV17 modeled in the yeast Saccharomyces cerevisiae
      orthologous gene SYM1 reveal their inability to take part in a high molecular
      weight complex.
AB  - Mitochondrial DNA depletion syndromes (MDDS) are a genetically and clinically
      heterogeneous group of human diseases caused by mutations in nuclear genes and
      characterized by a severe reduction in mitochondrial DNA (mtDNA) copy number
      leading to impaired energy production in affected tissues and organs. Mutations
      in the MPV17 gene, whose role is still elusive, were described as cause of the
      hepatocerebral form of MDDS and Navajo neuro-hepathopathy. The high degree of
      conservation observed between MPV17 and its yeast homolog SYM1 made the latter a
      good model for the study of the pathology. Here, we used Saccharomyces cerevisiae
      to elucidate the molecular consequences of seven MPV17 missense mutations
      identified in patients and localized in different protein domains. The phenotypic
      analysis of the appropriate sym1 mutant strains created demonstrated deleterious
      effect for all mutations regarding OXPHOS metabolism and mtDNA stability. We
      deepened the pathogenic effect of the mutations by investigating whether they
      prevented the correct protein localization into the mitochondria or affected the
      stability of the proteins. All the Sym1 mutant proteins correctly localized into
      the mitochondria and only one mutation predominantly affects protein stability.
      All the other mutations compromised the formation of the high molecular weight
      complex of unknown composition, previously identified both in yeast, cell
      cultures and mouse tissues, as demonstrated by the consistent fraction of the
      Sym1 mutant proteins found free or in not fully assembled complex, strengthening
      its role as protein forming part of a high molecular weight complex.

PMID- 30273400
TI  - Childhood socioeconomic position and physical capability in late-middle age in
      two birth cohorts from the Copenhagen aging and midlife biobank.
AB  - This study examines the association between childhood socioeconomic position and
      objective physical capability including new functional measures of potential
      relevance to a population in late-middle age. The study population covers two
      Danish birth cohorts followed-up in the Copenhagen Aging and Midlife Biobank (age
      48-58 years, 2009-2011, N = 4,204). Results from linear regression models
      revealed that being born in higher socioeconomic position was associated with
      higher jump height: Paternal occupational class four = 0.19 cm (95% confidence
      interval (CI): -0.44, 0.82), three = 0.59 cm (95% CI: -0.02, 1.19), two = 1.29 cm
      (95% CI: 0.64, 1.94), and one = 1.29 cm (95% CI: 0.45, 2.13) (reference = five);
      medium parental social class = 0.88 cm (95% CI: 0.03, 1.72) and high = 1.79 cm
      (95% CI: 0.94, 2.63) (reference = low). Higher childhood socioeconomic position
      was also associated with better chair rise performance and hand grip strength,
      while among women it was related to reduced flexibility: Medium parental social
      class = -1.31 cm (95% CI: -3.05, 0.42) and high = -2.20 cm (95% CI: -3.94, -0.47)
      (reference = low); unwed mother = 1.75 cm (95% CI: 0.36, 3.14) (reference =
      married). Overall, the findings suggest that higher childhood socioeconomic
      position is primarily related to moderately better scores in the most strenuous
      physical capability measures and hand grip strength among healthy adults in late
      middle age.

PMID- 30273401
TI  - Inflammatory cytokine oncostatin M induces endothelial activation in macro- and
      microvascular endothelial cells and in APOE*3Leiden.CETP mice.
AB  - AIMS: Endothelial activation is involved in many chronic inflammatory diseases,
      such as atherosclerosis, and is often initiated by cytokines. Oncostatin M (OSM)
      is a relatively unknown cytokine that has been suggested to play a role in both
      endothelial activation and atherosclerosis. We comprehensively investigated the
      effect of OSM on endothelial cell activation from different vascular beds and in
      APOE*3Leiden.CETP mice. METHODS AND RESULTS: Human umbilical vein endothelial
      cells, human aortic endothelial cells and human microvascular endothelial cells
      cultured in the presence of OSM express elevated MCP-1, IL-6 and ICAM-1 mRNA
      levels. Human umbilical vein endothelial cells and human aortic endothelial cells
      additionally expressed increased VCAM-1 and E-selectin mRNA levels. Moreover,
      ICAM-1 membrane expression is increased as well as MCP-1, IL-6 and E-selectin
      protein release. A marked increase was observed in STAT1 and STAT3
      phosphorylation indicating that the JAK/STAT pathway is involved in OSM
      signaling. OSM signals through the LIF receptor alfa (LIFR) and the OSM receptor
      (OSMR). siRNA knockdown of the LIFR and the OSMR revealed that simultaneous
      knockdown is necessary to significantly reduce MCP-1 and IL-6 secretion, VCAM-1
      and E-selectin shedding and STAT1 and STAT3 phosphorylation after OSM
      stimulation. Moreover, OSM administration to APOE*3Leiden.CETP mice enhances
      plasma E-selectin levels and increases ICAM-1 expression and monocyte adhesion in
      the aortic root area. Furthermore, Il-6 mRNA expression was elevated in the aorta
      of OSM treated mice. CONCLUSION: OSM induces endothelial activation in vitro in
      endothelial cells from different vascular beds through activation of the JAK/STAT
      cascade and in vivo in APOE*3Leiden.CETP mice. Since endothelial activation is an
      initial step in atherosclerosis development, OSM may play a role in the
      initiation of atherosclerotic lesion formation.

PMID- 30273402
TI  - Indoor residual spraying for kala-azar vector control in Bangladesh: A continuing
      challenge.
AB  - BACKGROUND: Visceral leishmaniasis (VL) in the Indian subcontinent is a fatal
      disease if left untreated. Between 1994 to 2013, the Ministry of Health of
      Bangladesh reported 1,09,266 cases of VL and 329 VL related deaths in 37 endemic
      districts. Indoor residual spraying (IRS) using dichlorodiphenyltrichloroethane
      (DDT) was used by the national programme in the 1960s to control malaria. Despite
      findings of research trials demonstrating that the synthetic pyrethroid
      deltamethrin 5 WP was very effective at reducing vector densities, no national VL
      vector control operations took place in Bangladesh between 1999 to early 2012. In
      2012, IRS using deltamethrin 5 WP was re-introduced by the national programme,
      which consisted of pre-monsoon spraying in eight highly endemic sub-districts
      (upazilas). The present study aims to evaluate the effectiveness of IRS on VL
      vectors, as well as the process and performance of the spraying activities by
      national programme staff. METHODS: Five highly endemic upazilas of Mymensingh
      district were purposively selected (Fulbaria, Trishal, Mukthagacha, Gaforgaon and
      Bhaluka) to conduct the present study using the WHO/TDR monitoring and evaluation
      tool kit. IRS operations, conducted by 136 squads/teams, and 544 spraymen, were
      observed using check lists and questionnaires included in the WHO/TDR monitoring
      and evaluation tool kit. A household (HH) acceptability survey of IRS was
      conducted in all study areas using a structured questionnaire in 600 HHs. To
      measure the efficacy of IRS, pre-IRS (two weeks prior) and post-IRS (at one and
      five months after), vector density was measured using CDC light traps for two
      consecutive nights. Bioassays, using the WHO cone-method, were carried out in 80
      HHs (40 sprayed and 40 unsprayed) to measure the effectiveness of the insecticide
      on sprayed surfaces. RESULTS: Of the 544 spraymen interviewed pre-IRS, 60%, 3%
      and 37% had received training for one, two and three days respectively. During
      spraying activities, 64% of the spraying squads had a supervisor in 4 upazilas
      but only one upazila (Mukthagacha) achieved 100% supervision of squads. Overall,
      72.8% of the spraying squads in the study upazilas had informed HHs members to
      prepare their houses prior to spraying. The required personal protective
      equipment was not provided by the national programme during our observations and
      the spraying techniques used by all sprayers were sub-standard compared to the
      standard procedure mentioned in the M&E toolkit. In the HH interviews, 94.8% of
      the 600 respondents said that all their living rooms and cattle sheds had been
      sprayed. Regarding the effectiveness measurements (i.e. reduction of vector
      densities), a total of 4132 sand flies were trapped in three intervals, of which
      3310 (80.1%) were P. argentipes; 46.5% (1540) males and 53.5% (1770) females. At
      one month post-IRS, P. argentipes densities were reduced by 22.5% but the 5
      months post-IRS reduction was only 6.4% for both male and female. The bioassay
      tests showed a mean corrected mortality of P. argentipes sand flies at one month
      post-IRS of 87.3% which dropped to 74.5% at 4 months post-IRS in three upazilas,
      which is below the WHO threshold level (80%). CONCLUSION: The national programme
      should conduct monitoring and evaluation activities to ensure high quality of IRS
      operations as a pre-condition for achieving a fast and sustained reduction in
      vector densities. This will continue to be important during the maintenance phase
      of VL elimination on the Indian subcontinent. Further research is needed to
      determine other suitable vector control option(s) when the case numbers are very
      low.

PMID- 30273403
TI  - Workload implications for clinic workflow with implementation of three
      dimensional printed customized bolus for radiation therapy: A pilot study.
AB  - Bolus is commonly used in radiation therapy to improve radiation dose
      distribution to the target volume, but commercially available products do not
      always conform well to the patient surface. Tumor control may be compromised,
      particularly for superficial tumors, if bolus does not conform well and air gaps
      exist between the patient surface and the bolus. Three-dimensional (3D) printing
      technology allows the creation of highly detailed, variable shaped objects,
      making it an attractive and affordable option for customized, patient-specific
      bolus creation. The use of 3D printing in the clinical setting remains limited.
      Therefore, the objective of this study was to assess the implications on time and
      clinical fit using a workflow for 3D printing of customized bolus in companion
      animals with spontaneous tumors treated with radiation therapy. The primary aim
      of this study was to evaluate the time required to create a clinical 3D printed
      bolus. The secondary aims were to evaluate the clinical fit of the bolus and to
      verify the skin surface dose. Time to segmentation and 3D printing were
      documented, while the clinical fit of the bolus was assessed in comparison to the
      bolus created in the treatment planner. The mean and median time from
      segmentation to generation of 3D printed boluses was 6.15 h and 5.25 h,
      respectively. The 3D printed bolus was significantly less deviated from the
      planned bolus compared to the conventional bolus (p = 0.0078) with measured dose
      under the bolus within 5% agreement of expected dose in 88% of the measurements.
      Clinically acceptable 3D printed customized bolus was successfully created for
      treatment within one working day. The most significant impact on time is the 3D
      printing itself, which therefore has minimal implications on personnel and
      staffing. Quality assurance steps are recommended when implementing a 3D printing
      workflow to the radiotherapy clinic.

PMID- 30273404
TI  - Blaunet: An R-based graphical user interface package to analyze Blau space.
AB  - McPherson's Blau space and affiliation ecology model is a powerful tool for
      analyzing the ecological competition among social entities, such as
      organizations, along a combination of sociodemographic characteristics of their
      members. In this paper we introduce the R-based Graphical User Interface (GUI)
      package Blaunet, an integrated set of tools to calculate, visualize, and analyze
      the statuses of individuals and social entities in Blau space, parameterized by
      multiple sociodemographic traits as dimensions. The package is able to calculate
      the Blau statuses at the nodal, dyadic, and meso levels based on three types of
      information: sociodemographic characteristics, group affiliations (e.g.,
      membership in groups/organizations), and network ties. To facilitate this,
      Blaunet has the following five main capabilities, it can: 1) identify a list of
      possible salient dimensions; 2) calculate, plot, and analyze niches for social
      entities by measuring the social distance along the salient dimensions between
      individuals affiliated with them; 3) generate Blau bubbles for individuals,
      thereby allowing the study of interpersonal influence of similar others even with
      limited or no network information; 4) capture niche dynamics cross-sectionally by
      calculating the intensity of exploitation from the carrying capacity and the
      membership rate; and 5) analyze the niche movement longitudinally by estimating
      the predicted niche movement equations. We illustrate these capabilities of
      Blaunet with example datasets.

PMID- 30273405
TI  - Comparison of the modified unbounded penalty and the LASSO to select predictive
      genes of response to chemotherapy in breast cancer.
AB  - Covariate selection is a fundamental step when building sparse prediction models
      in order to avoid overfitting and to gain a better interpretation of the
      classifier without losing its predictive accuracy. In practice the LASSO
      regression of Tibshirani, which penalizes the likelihood of the model by the L1
      norm of the regression coefficients, has become the gold-standard to reach these
      objectives. Recently Lee and Oh developed a novel random-effect covariate
      selection method called the modified unbounded penalty (MUB) regression, whose
      penalization function can equal minus infinity at 0 in order to produce very
      sparse models. We sought to compare the predictive accuracy and the number of
      covariates selected by these two methods in several high-dimensional datasets,
      consisting in genes expressions measured to predict response to chemotherapy in
      breast cancer patients. These comparisons were performed by building the Receiver
      Operating Characteristics (ROC) curves of the classifiers obtained with the
      selected genes and by comparing their area under the ROC curve (AUC) corrected
      for optimism using several variants of bootstrap internal validation and cross
      validation. We found consistently in all datasets that the MUB penalization
      selected a remarkably smaller number of covariates than the LASSO while offering
      a similar-and encouraging-predictive accuracy. The models selected by the MUB
      were actually nested in the ones obtained with the LASSO. Similar findings were
      observed when comparing these results to those obtained in their first
      publication by other authors or when using the area under the Precision-Recall
      curve (AUCPR) as another measure of predictive performance. In conclusion, the
      MUB penalization seems therefore to be one of the best options when sparsity is
      required in high-dimension. Further investigation in other datasets is however
      required to validate these findings.

PMID- 30273406
TI  - Impact of maternal western diet-induced obesity on offspring mortality and
      peripheral endocannabinoid system in mice.
AB  - Over two-thirds of adults in the United States are obese or overweight, which is
      largely due to chronic overconsumption of diets high in fats and sugars (i.e.,
      Western diet). Recent studies reveal that maternal obesity may predispose
      offspring to development of obesity and other metabolic diseases; however, the
      molecular underpinnings of these outcomes are largely unknown. The
      endocannabinoid system is an important signaling pathway that controls feeding
      behavior and energy homeostasis, and its activity becomes upregulated in the
      upper small intestinal epithelium of Western diet-induced obese mice, which
      drives overeating. In the current investigation, we examined the impact of
      chronic maternal consumption of Western diet on the expression and function of
      the endocannabinoid system in several peripheral organs important for food intake
      and energy homeostasis in offspring. Female C57BL/6Tac mice were fed a Western
      diet or low-fat/no-sucrose control chow for 10 weeks, then males were introduced
      for mating. Dams were maintained on their respective diets through weaning of
      pups, at which time pups were maintained on low-fat/no-sucrose chow for 10 weeks.
      Neonates born from dams fed Western diet, when compared to those born from mice
      fed control chow, unexpectedly displayed increases in mortality that occurred
      exclusively within six days following birth (greater than 50% mortality). Males
      comprised a larger fraction of surviving offspring from obese dams. Furthermore,
      surviving offspring displayed transient increases in body mass for first two days
      post weaning, and no marked changes in feeding patterns and endocannabinoid
      levels in upper small intestinal epithelium, pancreas, and plasma, or in
      expression of key endocannabinoid system genes in the upper small intestinal
      epithelium and pancreas at 10 weeks post-weaning. Collectively, these results
      suggest that maternal diet composition greatly influences survival of neonate
      C57BL/6Tac mice, and that surviving offspring from dams chronically fed a Western
      diet do not display marked changes in body mass, eating patterns, or expression
      and function of the endocannabinoid system in several peripheral organs important
      for feeding behavior and energy homeostasis.

PMID- 30273407
TI  - Noninvasive intracranial pressure assessment using otoacoustic emissions: An
      application in glaucoma.
AB  - The theory that glaucoma patients have a lower intracranial pressure (ICP) than
      healthy subjects is a controversial one. The aim of this study was to assess ICP
      noninvasively by determining the relationship between distortion product
      otoacoustic emission (DPOAE) phase and body position and to compare this
      relationship between patients with primary open angle glaucoma (POAG), patients
      with normal tension glaucoma (NTG), and controls. The relationship was also
      calibrated using published data regarding invasive measurements of ICP versus
      body position. DPOAEs were measured in 30 controls and 32 glaucoma patients (17
      POAG, 15 NTG) at the following body positions (assuming 90 degrees  as upright):
      45, 30, 20, 10, 0 (supine), -10, and -20 degrees . DPOAE phase had a clear,
      nonlinear relationship with body position. The mean DPOAE phase shifts between
      the two most extreme body positions (45 to -20 degrees ) were 73.6, 80.7, and
      66.3 degrees  for healthy, POAG, and NTG, respectively (P = 0.73), and the groups
      showed the same, nonlinear behaviour. This indicates that there is no evidence
      that glaucoma patients have a reduced ICP. When calibrated with invasive data,
      ICP and DPOAE phase were linearly related over an ICP of 3 mmHg. This suggests
      that, more broadly, DPOAEs could be used in the future to monitor changes in ICP
      in a clinical setting and to measure dynamic changes in ICP such as diurnal
      fluctuations or changes induced by certain medications.

PMID- 30273408
TI  - A bispecific immunotweezer prevents soluble PrP oligomers and abolishes prion
      toxicity.
AB  - Antibodies to the prion protein, PrP, represent a promising therapeutic approach
      against prion diseases but the neurotoxicity of certain anti-PrP antibodies has
      caused concern. Here we describe scPOM-bi, a bispecific antibody designed to
      function as a molecular prion tweezer. scPOM-bi combines the complementarity
      determining regions of the neurotoxic antibody POM1 and the neuroprotective POM2,
      which bind the globular domain (GD) and flexible tail (FT) respectively. We found
      that scPOM-bi confers protection to prion-infected organotypic cerebellar slices
      even when prion pathology is already conspicuous. Moreover, scPOM-bi prevents the
      formation of soluble oligomers that correlate with neurotoxic PrP species.
      Simultaneous targeting of both GD and FT was more effective than concomitant
      treatment with the individual molecules or targeting the tail alone, possibly by
      preventing the GD from entering a toxic-prone state. We conclude that
      simultaneous binding of the GD and flexible tail of PrP results in strong
      protection from prion neurotoxicity and may represent a promising strategy for
      anti-prion immunotherapy.

PMID- 30273409
TI  - Hatha yoga for acute, chronic and/or treatment-resistant mood and anxiety
      disorders: A systematic review and meta-analysis.
AB  - BACKGROUND: The aim of this study was to systematically investigate the
      effectiveness of hatha yoga in treating acute, chronic and/or treatment-resistant
      mood and anxiety disorders. METHODS: Medline, Cochrane Library, Current
      Controlled Trials, Clinical Trials.gov, NHR Centre for Reviews and Dissemination,
      PsycINFO and CINAHL were searched through June 2018. Randomized controlled trials
      with patients with mood and anxiety disorders were included. Main outcomes were
      continuous measures of severity of mood and anxiety symptoms. Cohen's d was
      calculated as a measure of effect size. Meta-analyses using a random effects
      model was applied to estimate direct comparisons between yoga and control
      conditions for depression and anxiety outcomes. Publication bias was visually
      inspected using funnel plots. RESULTS: Eighteen studies were found, fourteen in
      acute patients and four in chronic patients. Most studies were of low quality.
      For depression outcomes, hatha yoga did not show a significant effect when
      compared to treatment as usual, an overall effect size of Cohen's d -0.64 (95% CI
      = -1.41, 0.13) or to all active control groups, Cohen's d -0.13 (95% CI = -0.49,
      0.22). A sub-analysis showed that yoga had a significant effect on the reduction
      of depression compared to psychoeducation control groups, Cohen's d -0.52 (95% CI
      = -0.96, -0.08) but not to other active control groups, Cohen's d 0.28 (95% CI = 
      0.07, 0.63) For studies using a follow-up of six months or more, hatha yoga had
      no effect on the reduction of depression compared to active control groups,
      Cohen's d -0.14 (95% CI = -0.60, 0.33). Regarding anxiety, hatha yoga had no
      significant effect when compared to active control groups, Cohen's d -0.09 (95%
      CI = -0.47, 0.30). The I2 and Q-statistic revealed heterogeneity amongst
      comparisons. Qualitative analyses suggest some promise of hatha yoga for chronic
      populations. CONCLUSIONS: The ability to draw firm conclusions is limited by the
      notable heterogeneity and low quality of most of the included studies. With this
      caveat in mind, the results of the current meta-analysis suggest that hatha yoga
      does not have effects on acute, chronic and/or treatment-resistant mood and
      anxiety disorders compared to treatment as usual or active control groups.
      However, when compared to psychoeducation, hatha yoga showed more reductions in
      depression. It is clear that more high-quality studies are needed to advance the
      field.

PMID- 30273411
TI  - Is early silcrete heat treatment a new behavioural proxy in the Middle Stone Age?
AB  - The South African Middle Stone Age (MSA) has in recent years become increasingly
      important for our understanding of the emergence of 'modern human behaviours'.
      Several key innovations appeared in this context for the first time,
      significantly pre-dating their re-invention in the European Upper Palaeolithic.
      One of these innovations was heat treatment of stone to improve its quality for
      the production of stone tools. Heat treatment may even be the oldest well
      documented technique used to intentionally alter the properties of materials in
      general. It is commonly thought of as requiring the skilled use of fire, a high
      degree of planning depth and complex cognitive abilities. However, to work on
      these fundamental concepts we need to analyse the techniques and procedures used
      to heat-treat and we need to understand what they imply. In this paper, we
      present a direct and expedient comparison between the technical complexities of
      four alternative heat treatment procedures by coding the behaviours required for
      their set-up in so-called cognigrams, a relatively new method for understanding
      complexity based on the problem-solution distance. Our results show that although
      the techniques significantly differ in complexity, the techniques used in the MSA
      fall within the range of complexities known from other MSA techniques. Heat
      treatment in above-ground fires, as it was practised during this period in South
      Africa, was even one of the most complex techniques at the time of its invention.
      Early heat treatment can therefore be considered an important behavioural proxy
      that may shed light on the behaviour and socioeconomic structure of past groups.
      The implications of this are highlighted by the ongoing debate about 'modernity',
      'behavioural flexibility' and 'complex cognition' of early anatomically modern
      humans in Africa.

PMID- 30273410
TI  - What are the perceptions about running and knee joint health among the public and
      healthcare practitioners in Canada?
AB  - OBJECTIVES: To evaluate the perceptions of the general public and healthcare
      practitioners (HCP) in Canada about the relationship between running and knee
      joint health, and to explore HCP's usual recommendations to runners with knee
      osteoarthritis (KOA). METHODS: Non-runners and runners (with and without KOA) and
      HCP completed an online survey regarding the safety of running for knee joint
      health. HCP also provided information related to usual clinical recommendations.
      Proportions of agreement were compared between non-runners and runners. RESULTS:
      A total of 114 non-runners, 388 runners and 329 HCP completed the survey.
      Overall, running was perceived as detrimental for the knee joint by 13.1% of the
      general public, while 25.9% were uncertain. More uncertainty was reported
      regarding frequent (33.9%) and long-distance (43.6%) running. Statistical
      analyses revealed greater proportions of non-runners perceiving running
      negatively compared with runners. Overall, 48.4% believed that running in the
      presence of KOA would lead to disease progression, while 53.1% believed running
      would lead to premature arthroplasty. In HCP, 8.2%, 9.1% and 22.2% perceived that
      running in general, running frequently, or running long-distances are risk
      factors for KOA, respectively. 37.1% and 2.7% of HCP typically recommended
      patients with KOA to modify their running training or to quit running,
      respectively. CONCLUSION: High rates of uncertainty among the general public and
      HCP in Canada outline the need for further studies about running and knee joint
      health. Filling knowledge gaps will help inform knowledge translation strategies
      to better orientate the general public and HCP about the safety of running for
      knee joint health.

PMID- 30273412
TI  - Effects of breeding center, age and parasite burden on fecal triiodothyronine
      levels in forest musk deer.
AB  - The objective of this study was to evaluate the effects of sex, breeding center
      and age on fecal triiodothyronine levels in captive forest musk deer Moschus
      berezovskii, and to explore the age-intensity model of gastrointestinal
      parasites. Furthermore, the association between fecal triiodothyronine levels and
      parasite egg shedding was also analyzed. We collected musk deer fecal samples
      from two breeding centers located in Shaanxi and Sichuan province, China. Enzyme
      linked immunosorbent assays were utilized to estimate the fecal triiodothyronine
      concentrations and profiles, and fecal parasite eggs or oocysts were counted
      using the McMaster technique. Female deer from both breeding centers consistently
      showed higher triiodothyronine concentrations than those observed in males, which
      indicates that a distinct physiology pattern occurs by sex. The triiodothyronine
      concentration in Sichuan breeding center was significantly higher than that in
      Shaanxi center for both sexes, suggesting that differences in environment, diet
      and management practices are likely to affect the metabolism. In addition, a
      negative relationship between triiodothyronine concentrations and age was found
      (r = - 0.75, p < 0.001), and parasite egg shedding was also negatively associated
      with age (r = - 0.51, p < 0.001), by which we can infer that older animals
      evolves a more developed immune system. Finally, a positive association between
      parasite egg shedding and triiodothyronine levels was found, which could be
      explained by the additional energy metabolism resulting from parasitic infection.
      Results from this study might suggest metabolic and immunological adaptations in
      forest musk deer. These baseline data could be used to unveil metabolic status
      and establish parasite control strategies, which has great potential in captive
      population management as well as their general health evaluations.

PMID- 30273413
TI  - Dietary calcium intake and food sources among Chinese adults in CNTCS.
AB  - BACKGROUND: Calcium is one of the essential micronutrients in the human body and
      is well-known for its important role in keeping bones and teeth healthy. However,
      calcium deficiency is a very common nutritional problem in the world and
      especially in China. The aim of this research was to determine the dietary
      calcium intake of Chinese adults and the corresponding food sources based on data
      from the 2015 China Nutritional Transition Cohort Study. METHODS: We obtained
      dietary data from Chinese adults ages 18 to 64 years in 15 provinces, autonomous
      regions, and municipalities using 3 consecutive days combined with the household
      weighing method. We used the China Food Composition (book 1, 2nd edition) to
      calculate the calcium intake from each food category. We regarded the percentage
      of participants with a calcium intake median below the estimated average
      requirement as the level of calcium inadequacy in the overall population.
      RESULTS: We divided the participants into 2 age groups, 18-49 years and 50-64
      years, which included 6,630 and 5,307 participants, respectively. The groups'
      dietary calcium intake medians were 324.8 milligrams per day (mg/d) and 332.7
      mg/d, respectively, and the calcium inadequacies were 92.9% and 96.0%,
      correspondingly. The median calcium intake for the whole study population was
      328.3 mg/d, and the inadequacy was 94.3%, which improved with higher education,
      income, and urbanization levels. The main food sources of dietary calcium among
      the study population were vegetables, legumes, and cereals, which contributed
      30.2%, 16.7%, and 14.6%, respectively. Milk and dairy products contributed 6.7%
      to the study population but varied with the urbanization level to 15.0%, 6.1%,
      6.3%, and 2.0% in urban, suburban, county, and rural areas, respectively.
      CONCLUSION: These findings highlight the importance of nutrition education and
      intervention for Chinese adults to improve their dietary structures and increase
      milk and dairy products intake to consume adequate calcium.

PMID- 30273414
TI  - Phylogenetically Novel Uncultured Microbial Cells Dominate Earth Microbiomes.
AB  - To describe a microbe's physiology, including its metabolism, environmental
      roles, and growth characteristics, it must be grown in a laboratory culture.
      Unfortunately, many phylogenetically novel groups have never been cultured, so
      their physiologies have only been inferred from genomics and environmental
      characteristics. Although the diversity, or number of different taxonomic groups,
      of uncultured clades has been studied well, their global abundances, or numbers
      of cells in any given environment, have not been assessed. We quantified the
      degree of similarity of 16S rRNA gene sequences from diverse environments in
      publicly available metagenome and metatranscriptome databases, which we show have
      far less of the culture bias present in primer-amplified 16S rRNA gene surveys,
      to those of their nearest cultured relatives. Whether normalized to scaffold read
      depths or not, the highest abundances of metagenomic 16S rRNA gene sequences
      belong to phylogenetically novel uncultured groups in seawater, freshwater,
      terrestrial subsurface, soil, hypersaline environments, marine sediment, hot
      springs, hydrothermal vents, nonhuman hosts, snow, and bioreactors (22% to 87%
      uncultured genera to classes and 0% to 64% uncultured phyla). The exceptions were
      human and human-associated environments, which were dominated by cultured genera
      (45% to 97%). We estimate that uncultured genera and phyla could comprise 7.3 *
      1029 (81%) and 2.2 * 1029 (25%) of microbial cells, respectively. Uncultured
      phyla were overrepresented in metatranscriptomes relative to metagenomes (46% to
      84% of sequences in a given environment), suggesting that they are viable.
      Therefore, uncultured microbes, often from deeply phylogenetically divergent
      groups, dominate nonhuman environments on Earth, and their undiscovered
      physiologies may matter for Earth systems. IMPORTANCE In the past few decades, it
      has become apparent that most of the microbial diversity on Earth has never been
      characterized in laboratory cultures. We show that these unknown microbes,
      sometimes called "microbial dark matter," are numerically dominant in all major
      environments on Earth, with the exception of the human body, where most of the
      microbes have been cultured. We also estimate that about one-quarter of the
      population of microbial cells on Earth belong to phyla with no cultured
      relatives, suggesting that these never-before-studied organisms may be important
      for ecosystem functions. Author Video: An author video summary of this article is
      available.

PMID- 30273416
TI  - Erratum: Publisher Correction: Symbiodinium genomes reveal adaptive evolution of
      functions related to coral-dinoflagellate symbiosis.
AB  - [This corrects the article DOI: 10.1038/s42003-018-0098-3.].

PMID- 30273417
TI  - Erratum: Author Correction: The EphA2 receptor is activated through induction of
      distinct, ligand-dependent oligomeric structures.
AB  - [This corrects the article DOI: 10.1038/s42003-018-0017-7.].

PMID- 30273415
TI  - Genome-wide association study of developmental dysplasia of the hip identifies an
      association with GDF5.
AB  - Developmental dysplasia of the hip (DDH) is the most common skeletal
      developmental disease. However, its genetic architecture is poorly understood. We
      conduct the largest DDH genome-wide association study to date and replicate our
      findings in independent cohorts. We find the heritable component of DDH
      attributable to common genetic variants to be 55% and distributed equally across
      the autosomal and X-chromosomes. We identify replicating evidence for association
      between GDF5 promoter variation and DDH (rs143384, effect allele A, odds ratio
      1.44, 95% confidence interval 1.34-1.56, P = 3.55 * 10-22). Gene-based analysis
      implicates GDF5 (P = 9.24 * 10-12), UQCC1 (P = 1.86 * 10- 10), MMP24 (P = 3.18 *
      10-9), RETSAT (P = 3.70 * 10- 8) and PDRG1 (P = 1.06 * 10- 7) in DDH
      susceptibility. We find shared genetic architecture between DDH and hip
      osteoarthritis, but no predictive power of osteoarthritis polygenic risk score on
      DDH status, underscoring the complex nature of the two traits. We report a
      scalable, time-efficient recruitment strategy and establish for the first time to
      our knowledge a robust DDH genetic association locus at GDF5.

PMID- 30273418
TI  - Report on the status of women occupying leadership roles in oncology.
AB  - Background: While the global workforce is approaching gender parity, women occupy
      a small number of management level positions across most professions, including
      healthcare. Although the inclusion of women into the membership of many oncology
      societies has increased, the under-representation of women in leadership roles
      within international and national oncology societies remains relatively
      consistent. Moreover, the exact status of women participating as board members or
      presidents of oncology societies or as speakers at oncology congresses was
      undocumented to date. Methods: The database used in this analysis was derived
      from data collection performed by the European Society for Medical Oncology for
      the years 2015-2016 and data analyses performed using the Statistical Analysis
      Software V.9.3 and R language for statistical computing V.3.4.0 by Frontier
      Science Foundation-Hellas. The literature search was performed by the authors.
      Results: We report the presence of a gender gap within oncology. Results
      regarding the under-representation of women occupying leadership roles in
      oncology show female participation as members of the board or presidents of
      national and international oncology societies and as invited speakers at oncology
      congresses remains below 50% in the majority of societies included in this
      analysis. Women in leadership positions of societies was associated with a higher
      percentage of female invited speakers at these societies' congresses (p=0.006).
      Conclusion: The full contribution that can be attained from using the potential
      of women in leadership roles is currently under-realised. Examples of how gender
      and minority participation in organisations improves outcomes and creativity are
      provided from science, clinical practice and industry that show outcomes are
      greatly improved by collective participation of both men and women. Although
      there are programmes in place in many oncology organisations to improve this
      disparity, the gender gap is still there. Ongoing discussion may help to create
      more awareness in the effort to accelerate the advancement of women within
      oncology.

PMID- 30273419
TI  - Sizing Up the Uncultured Microbial Majority.
AB  - Predicting the total number of microbial cells on Earth and exploring the full
      diversity of life are fundamental research concepts that have undergone paradigm
      shifts in the genomic era. In this issue, Lloyd and colleagues (K. G. Lloyd, A.
      D. Steen, J. L. Ladau, J. Yin, and L. Crosby, mSystems 3:e00055-18,
      https://doi.org/10.1128/mSystems.00055-18, 2018) present results that combine
      these two concepts by estimating the total diversity of all cells from Earth's
      environments. Leveraging publicly available amplicon, metagenomic, and
      metatranscriptomic datasets, they determined that nearly all environments are
      dominated by uncultured lineages, with the exception of humans and human
      associated habitats. They define a new concept: phylogenetically diverse
      noncultured cells (PDNC). Unlike viable but nonculturable cells (VBNC), PDNC are
      microorganisms for which traditional isolation techniques may never succeed.
      Lloyd et al. estimate that the majority of microorganisms in Earth's ecosystems
      may be PDNC and conclude that culture-independent methods combined with
      innovative culturing techniques may be required to understand the ecology and
      physiology of these abundant and divergent microorganisms.

PMID- 30273422
TI  - Building highly reliable office-based surgery [Editorial].

PMID- 30273423
TI  - Endoscopic view of the carotid artery in the sphenoid sinus.

PMID- 30273420
TI  - Gender-related challenges facing oncologists: the results of the ESMO Women for
      Oncology Committee survey.
AB  - Background: Although women account for a growing proportion of the oncology
      workforce, there is evidence they are under-represented in leadership roles. To
      gain further insights into this issue and extend understanding of gender
      challenges, the European Society for Medical Oncology Women for Oncology (W4O)
      Committee undertook a survey of female and male oncologists in 2016. Design: The
      2016 W4O questionnaire included questions on (1) Demographics and professional
      environment, (2) Gender impact on career development, (3) Challenges for career
      progression and inappropriate behaviour experienced in the workplace, (4)
      Barriers for gender parity and (5) The gender gap. Between July and September
      2016, the online survey was available to male and female clinical and academic
      oncology healthcare professionals in the EU and internationally. Results:
      Responses were analysed from 462 oncologists, of whom 76.7 % were women. Of
      female respondents, 45.5 % had a managerial or leadership role, compared with 65
      % of male respondents (p<0.001). Men were more likely to have leadership roles,
      even in clinical teams with more women than men. Women respondents were more
      likely to consider their gender had a major impact on their career than men: 35.9
      % vs 20.9 % (p<0.001). The biggest challenge to career progression for women was
      work and family balance (64.2%). Of female respondents, 14.4 % believed there had
      been significant or major progress in closing the gender pay gap compared with
      39.3 % of men (p<0.001). Of female participants, 37.7 % reported they had
      encountered unwanted sexual comments by a superior or colleague. Conclusions: New
      initiatives are needed to address under-representation of women oncologists in
      leadership roles, including greater and concrete promotion of work-life balance,
      development and leadership training for women, and more support for flexible
      working. The fact that over a third of women in the survey had encountered
      unwanted sexual comments at work is of great concern and must be urgently
      addressed.

PMID- 30273424
TI  - Nonarytenoid laryngeal granulomas.

PMID- 30273421
TI  - Erratum: Author Correction: Evolutionary history of plant hosts and fungal
      symbionts predicts the strength of mycorrhizal mutualism.
AB  - [This corrects the article DOI: 10.1038/s42003-018-0120-9.].

PMID- 30273425
TI  - Button battery insertion in nose manifested as infraorbital cellulitis.

PMID- 30273426
TI  - Efficient closure of earlobe cleft with biopsy punch.

PMID- 30273427
TI  - Salivary alpha-amylase levels in vertigo: Can it be an autonomic dysfunction?
AB  - We aim to demonstrate possible autonomic dysfunction based on salivary alpha
      amylase measurements during and after the vertigo attacks associated with Meniere
      disease (MD) and benign paroxysmal positional vertigo (BPPV). Patients admitted
      to the emergency room with a diagnosis of vertigo attacks caused by either MD (n
      = 15) or BPPV (n = 9) constituted the study groups. The control group (n = 10)
      consisted of volunteer patients admitted to the emergency department with minor
      soft-tissue trauma. The first saliva samples were obtained immediately during the
      attacks and the second and third samples were obtained on the third and fifteenth
      days of the attack, respectively. In the controls, the first sample was obtained
      after admission to the hospital and the second sample was obtained on the third
      day. Salivary alpha-amylase levels were evaluated. The difference between
      salivary alpha-amylase levels in patients with MD and BPPV was not significant.
      The amylase value measured early after the BPPV attack was significantly lower
      than that of the controls (p = 0.008). Although not significant, an undulating
      pattern of salivary alpha-amylase levels was observed with both diseases. An
      autonomic imbalance could be partly demonstrated by salivary alpha-amylase
      measurement early after the attack in patients with BPPV. Therefore, amylase may
      be a promising marker that is worth further investigation.

PMID- 30273428
TI  - Mucocele development after endoscopic sinus surgery for nasal polyposis: A long
      term analysis.
AB  - The aim of the present study was to determine the prevalence of long-term
      mucocele development after functional endoscopic sinus surgery (FESS) for nasal
      polyposis, to search for a statistical relationship with preoperative variables
      and to analyze the management of this complication. A retrospective analysis of
      153 patients who underwent FESS for nasal polyposis, with a minimum of 7 years of
      follow-up, was performed. Mucocele diagnosis was based on regular clinical and
      radiologic evaluation. Univariate and multivariate statistical analysis was
      performed. The postoperative mucocele rate was 13.1% (20 patients). The mean
      delay between surgery and mucocele diagnosis was 6.25 years. A high preoperative
      Lund-Mackay score (>19) was a risk factor for postoperative mucocele (p = 0.04).
      Asthma and aspirin intolerance did not increase the risk of this complication.
      Endoscopic marsupialization of mucoceles was successful in 19 patients, with only
      one recurrent frontal mucocele. One patient required external approaches for two
      frontal mucoceles. In conclusion, mucocele risk after FESS for nasal polyposis is
      significant, especially in case of a high preoperative Lund-Mackay score (>19).
      Long-term clinical follow-up is recommended, imaging being prescribed based on
      symptoms or abnormal findings on clinical examination. Endoscopic
      marsupialization is very effective, but frontal mucoceles are more likely to
      recur.

PMID- 30273429
TI  - Positivity rates of in vitro inhalant/respiratory and food allergy tests in the
      northern midwestern United States.
AB  - Rates of allergy-test positivity vary by country and by regions within countries.
      Several studies have looked at allergy test results to determine the most common
      allergens. Many of these studies have been based on surveys or on studies of
      small numbers of tests. Positivity rates for allergy tests are poorly defined in
      the northern midwestern region of the United States. We conducted a study to
      identify the rates of positive allergy tests for both inhalant/respiratory
      allergens and food allergens in the upper Midwest. We extracted from our
      laboratory database the results of all test samples sent for one of eight
      allergen panels that had been analyzed between Sept. 1, 2014, and Sept. 1, 2015.
      All testing was performed at The Cleveland Clinic with the Phadia ImmunoCAP
      system. The percentage of positive tests, the distribution of the most frequently
      positive tests, and the class of in vitro responses were identified. A total of
      148,628 test results for 63 different allergens were identified. Of the 125,190
      tests for inhalant/respiratory allergens, the most frequently positive were dog
      dander (24% of tests), cat dander (23%), dust mites (23% for both
      Dermatophagoides pteronyssinus and Dermatophagoides farinae), and June grass
      (21%). Of the 23,438 food tests, the most frequently positive test results were
      for milk (18%), peanut (17%), wheat (16%), and egg white (15%). Most of the
      results fell into classes 1 through 3, although there was still a notable number
      of very high responses (class 5 and 6). These findings suggest that there is wide
      variability in the positivity of in vitro allergy tests and that the likelihood
      of a positive result in screening panels can be estimated. Evaluating such rates
      will help identify the most and least common allergens and will help to cost
      effectively refine allergy screening panels.

PMID- 30273430
TI  - Acute infectious laryngitis: A case series.
AB  - Although acute laryngitis is common, it is often managed by primary physicians.
      Therefore, video images documenting its signs are scarce. This series includes 7
      professional voice users who previously had undergone baseline
      strobovideolaryngscopy (SVL) during routine examinations or during evaluations
      for other complaints and who returned with acute laryngitis. Sequential SVL
      showed not only the expected erythema, edema, cough, and dysphonia, but also new
      masses in 5 of the 7 subjects. All the signs returned to baseline. This series is
      reported to highlight the reversible structural changes that can be expected in
      patients with acute laryngitis and the value of conservative management.

PMID- 30273431
TI  - No difference in disease-free survival after oral cancer resection with close
      tumor margins in patients with and without postoperative radiotherapy.
AB  - We conducted a retrospective follow-up study to determine if adjunctive
      radiotherapy (RT) affected disease-free survival in patients with oral squamous
      cell carcinoma (SCC) who were found to have close surgical margins after tumor
      resection. Our study population was made up of 110 patients-72 men and 38 women,
      aged 30 to 94 years (median: 66) at the time of diagnosis. Their follow-up ranged
      from 12 days to 5.2 years (median: 3.6 yr). Of this group, 40 patients had free
      margins, 55 patients had close margins, and 15 had involved margins after
      surgery. Only 31 of these patients received postoperative RT, including 17 who
      had close margins. We would expect to find better postoperative local tumor
      control with combined surgery and RT, but we found no statistically significant
      difference in disease-free survival between the surgery-plus-RT group and the
      surgery-only group (p = 0.72). We also found no significant difference in disease
      free survival between patients with a tumor of the floor of mouth and those with
      a tumor of the tongue (p = 0.34). In the study population as a whole, the disease
      free survival rate was 81.0% and the overall survival rate was 78.2%. Our
      findings support the trend toward a watch-and-wait approach before initiating
      postoperative RT for patients with close surgical margins. The decision should be
      carefully discussed between the surgeon, the oncologic radiotherapist, and the
      patient.

PMID- 30273432
TI  - Outcomes of reapplication to otolaryngology residency: A prospective cohort
      study.
AB  - Although the field of otolaryngology has experienced a decline in the number of
      applicants to our residency programs, otolaryngology remains a highly competitive
      field with an extremely strong applicant pool. Many highly qualified candidates
      cannot obtain a position in our field each year, and many of these candidates
      choose to reapply the next year. Data are lacking regarding reapplicants' success
      rate and the best gap year employment and training options for these
      reapplicants. Reapplicants were studied prospectively via a two-stage survey
      during the 2014-2015 and 2015-2016 application cycles. Success rates for the
      overall group were compared to those from published data, and success rates
      between subgroups were also compared. First-time reapplicants in the study
      performed extremely well. Their match rate (19/22) was not significantly
      different from that of traditional otolaryngology applicants (551/619, p = 0.73)
      and was significantly higher than that of nontraditional applicants not in our
      cohort (23/62, p < 0.001). No significant difference was found between applicants
      by employment/training activities, with both researchers (11/12) and surgical
      interns (8/10, p = 0.57) performing well. Predictors of reapplicant success could
      not be assessed because only 3 reapplicants in the cohort were unsuccessful.
      First-time otolaryngology reapplicants remain a highly competitive group of
      applicants to our field, regardless of employment/training activities undertaken
      after graduating medical school.

PMID- 30273433
TI  - The role of meteorologic factors and air pollution on the frequency of pediatric
      epistaxis.
AB  - Fluctuations in atmospheric temperature, humidity, and air pollution are
      associated with the incidence of epistaxis. To date, no study in the literature
      has evaluated the effect of air pollution and meteorologic conditions on the
      pediatric population. We aimed to evaluate the effect of meteorologic factors and
      air pollution on the frequency of epistaxis in children. Children presenting to
      an outpatient clinical setting at a tertiary care hospital during a 5-year period
      (July 1, 2009, to June 30, 2014) and diagnosed with epistaxis formed the study
      population. Daily temperature and humidity parameters and average daily
      atmospheric water vapor pressure, average daily concentration of particulate
      matter <10 MUm in diameter, and sulfur dioxide readings were obtained. The
      distribution of daily parameters was analyzed. Of the 1,559 children with the
      primary diagnosis of epistaxis, data from 1,330 children were analyzed after
      excluding patients with coexisting pathologies. Positive correlations were found
      between the frequency of epistaxis and both the average daily temperature and the
      difference between the maximum and minimum daily temperature. There was a
      negative correlation between the epistaxis frequency and the average daily
      humidity, the difference between the maximum and minimum daily humidity, the
      average daily concentration of particulate matter, and the sulfur dioxide levels.
      Our findings suggest that epistaxis in children is related to high temperatures
      and low humidity.

PMID- 30273434
TI  - Renal cell carcinoma metastatic to the sinonasal cavity: A review and report of 8
      cases.
AB  - Renal cell carcinoma (RCC) metastatic in the sinonasal cavity is rare. In many
      cases, it represents the initial presentation of RCC. We conducted a
      retrospective chart review to report the clinical presentation, imaging, and
      treatment of RCC metastases in the sinonasal cavity at two tertiary care referral
      centers. Our population was made up of 8 patients-6 men and 2 women, aged 55 to
      86 years (mean: 66.9; median: 63.5)-who had been diagnosed with cancer in the
      sinonasal cavity. The most common complaints were epistaxis, nasal obstruction,
      and diplopia. Cancers were located in the ethmoid sinus (n = 3), nasal cavity (n
      = 2), sphenoid sinus (n = 2), and maxillary sinus (n = 1). Local treatment
      involved resection and adjuvant radiotherapy in 4 patients, surgery alone in 2
      patients, and radiotherapy alone in the other 2. The lesion was embolized before
      surgery in 4 cases. We also performed a critical review of similar published
      cases. Our literature review covered 53 cases of RCC metastatic to the sinonasal
      cavity, including ours. Metastases were the first presentation of RCC in 24 of
      these cases (45.3%); in our series, the metastases led to the diagnosis of the
      primary RCC in 3 cases (37.5%). In the 53 reported cases, metastatic resection
      was performed on 35 patients (66.0%). Survival data were available for 22 of
      these operated patients, and 17 of them achieved a complete local response.
      Adjunctive radiotherapy was not associated with a better local response. Overall
      survival was significantly better in patients who had an isolated metastasis
      rather than multiple metastases (p = 0.013). There was no difference in overall
      survival between patients whose metastasis represented the initial presentation
      of RCC and those whose metastasis did not (p = 0.95). We recommend that sinonasal
      metastasis be suspected in the event of unilateral nasal bleeding or nasal
      obstruction in patients diagnosed with RCC. Embolization may prevent abundant
      bleeding during removal. Surgery may improve the quality of life of these
      patients while decreasing nasal obstruction and bleeding.

PMID- 30273435
TI  - Upper aerodigestive tract frostbite from inhalation of automotive nitrous oxide.
AB  - Nitrous oxide, a cryogenic gas, may be abused as an inhalant for its euphoric
      properties. If inhaled, nitrous oxide may cause frostbite to the oral cavity and
      upper aerodigestive tract, with possible airway compromise due to edema. In this
      article we describe what is, to the best of our knowledge, the first case of
      intentional inhalation of nitrous oxide from an automotive nitrous oxide canister
      and discuss the management and mechanism of the patient's injury.

PMID- 30273436
TI  - Nondisseminated rhinosporidiosis with multisite involvement in the head and neck.
AB  - Rhinosporidiosis is a communicable disease prevalent in tropical countries that
      affects one or more mucocutaneous sites such as the nasal cavity, pharynx, skin,
      bronchus, genitals, and bone, in isolation or together. We report a case of
      multicentric rhinosporidiosis involving the nasal cavity, oropharynx, larynx, and
      cheek skin without disseminated disease outside the head and neck. Although the
      appearance of mucocutaneous lesions in our patient was similar to that of
      papilloma or neoplasm, the distinct clinicopathologic characteristics of the
      rhinosporidiosis guided us in managing the case successfully. In our own
      experience with 11 patients with rhinosporidiosis on whom we operated over the
      past 5 years, the nasal cavity and pharynx were the most commonly involved sites
      in the head and neck. Surgical excision of all lesions along with cauterization
      of the base and long-term dapsone therapy is the current standard of care for
      multicentric rhinosporidiosis.

PMID- 30273437
TI  - Audiologic profile in patients with ankylosing spondylitis: A controlled study of
      30 patients.
AB  - Recent studies have identified sensorineural hearing loss as a possible
      manifestation of ankylosing spondylitis. We conducted a study of 30 patients with
      ankylosing spondylitis to characterize their audiologic profile and to correlate
      their disease activity and functional indices with their hearing thresholds. The
      study group was made up of 18 men and 12 women, aged 25 to 58 years (mean: 46.5),
      who were diagnosed with ankylosing spondylitis. We compared their findings with a
      socially and demographically matched group of 30 healthy controls. All 60
      participants underwent an audiologic assessment, consisting of pure-tone
      audiometry, speech audiometry, and tympanometry. We used validated indices to
      assess disease activity and functional status, and we compiled information on the
      time of diagnosis and the types of medications used to treat the ankylosing
      spondylitis. We found that the average of the mean air-conduction thresholds at
      0.5, 1, 2, and 4 kHz in the ankylosing spondylitis group was significantly worse
      than that of the controls (p = 0.004). A statistically significant difference was
      observed at frequencies greater than 3 kHz (p < 0.05). A subgroup of case
      patients who used only a tumor necrosis factor-alpha inhibitor exhibited better
      hearing thresholds than patients who used other drugs (p = 0.01). Differences in
      functional and disease activity scores between case patients with and without
      hearing loss were not statistically significant. We found that patients with
      ankylosing spondylitis did indeed have a greater prevalence of sensorineural
      hearing loss but that it was not correlated with either disease activity or
      functional status.

PMID- 30273438
TI  - Bilateral spontaneous temporomandibular joint herniation: A case report and
      literature review.
AB  - In this article we report the case of a 41-year-old man with bilateral aural
      fullness and hearing loss. On examination he was found to have bilateral,
      dehiscent anterior canal walls with herniation of the mandibular condyle. This
      herniation partially obstructed the canals and contributed to his symptoms. To
      the best of our knowledge, this is only the third reported case of bilateral
      spontaneous temporomandibular joint herniation, and only 28 cases of unilateral
      spontaneous herniation can be found in the English language literature. While it
      is a rare phenomenon, it should be considered when evaluating a patient with
      fluctuating ear symptoms.

PMID- 30273439
TI  - Histoplasmosis of the head and neck in the immunocompetent patient: Report of 2
      cases.
AB  - Histoplasmosis of the head and neck is rarely seen in immunocompetent patients.
      We report 2 new cases of histoplasmosis of the head and neck in immunocompetent
      patients, one an 80-year-old man and the other a 57-year-old man. The older man
      presented with oral cavity histoplasmosis; his symptoms included pain, dysphagia,
      and ulcerative lesions. The younger man had laryngeal histoplasmosis, which
      resulted in hoarseness and dyspnea. We discuss the methods of diagnosis and the
      classic findings in histoplasmosis, including the microscopic appearance of
      caseating granulomas, the results of periodic acid-Schiff staining and Gomori
      staining, and antibody detection of histoplasmosis. We also review the treatment
      options with antifungals, including amphotericin B and the oral conazole drugs.
      With an accurate diagnosis and proper treatment, both of our patients recovered
      well and their symptoms resolved. Because their symptoms overlapped with those of
      other, more common disease processes, an accurate diagnosis of these patients was
      essential to treating their infection.

PMID- 30273440
TI  - Primary pleomorphic adenoma of the middle ear and mastoid.

PMID- 30273441
TI  - Endoscopic view of antrochoanal polyp with a dental implant.

PMID- 30273442
TI  - Dual-specificity phosphatase 6 deletion protects the colonic epithelium against
      inflammation and promotes both proliferation and tumorigenesis.
AB  - The Ras/mitogen-activated protein kinase (MAPK) pathway controls fundamental
      cellular processes such as proliferation, differentiation, and apoptosis. The
      dual-specificity phosphatase 6 (DUSP6) regulates cytoplasmic MAPK signaling by
      dephosphorylating and inactivating extracellular signal-regulated kinase (ERK1/2)
      MAPK. To determine the role of DUSP6 in the maintenance of intestinal
      homeostasis, we characterized the intestinal epithelial phenotype of Dusp6
      knockout (KO) mice under normal, oncogenic, and proinflammatory conditions. Our
      results show that loss of Dusp6 increased crypt depth and epithelial cell
      proliferation without altering colonic architecture. Crypt regeneration capacity
      was also enhanced, as revealed by ex vivo Dusp6 KO organoid cultures.
      Additionally, loss of Dusp6 induced goblet cell expansion without affecting
      enteroendocrine and absorptive cell differentiation. Our data also demonstrate
      that Dusp6 KO mice were protected from acute dextran sulfate sodium-induced
      colitis, as opposed to wild-type mice. In addition, Dusp6 gene deletion markedly
      enhanced tumor load in Apc Min/+ mice. Decreased DUSP6 expression by RNA
      interference in HT29 colorectal cancer cells enhanced ERK1/2 activation levels
      and promoted both anchorage-independent growth in soft agar as well as invasion
      through Matrigel. Finally, DUSP6 mRNA expression in human colorectal tumors was
      decreased in advanced stage tumors compared with paired normal tissues. These
      results demonstrate that DUSP6 phosphatase, by controlling ERK1/2 activation,
      regulates colonic inflammatory responses, and protects the intestinal epithelium
      against oncogenic stress.

PMID- 30273443
TI  - Plasma cells: The programming of an antibody-secreting machine.
AB  - Antibodies are an essential component of our immune system, underpinning the
      effectiveness of both the primary immune response to microbial pathogens and the
      protective and long-lived immunity against re-challenge. All antibodies are
      produced by relatively rare populations of plasmablasts and plasma cells,
      collectively termed antibody-secreting cells (ASCs). It is now apparent that ASCs
      are unique in the body in terms of their gene expression program and metabolic
      pathways that enable these cells to have an extraordinary rate of immunoglobulin
      gene transcription, translation, assembly and secretion. In this review we will
      discuss the cellular, metabolic and molecular specialization that allows ASCs to
      maintain such high rates of antibody production, in some cases for the life of
      the individual. Throughout the review we will link these exquisite cellular and
      molecular adaptations to the major regulators of ASC gene expression, in an
      attempt to define how the ASC phenotype and function is genetically programmed.

PMID- 30273444
TI  - Clinical commissioning of a new patient positioning system, SyncTraX FX4, for
      intracranial stereotactic radiotherapy.
AB  - BACKGROUND & AIMS: A new real-time tracking radiotherapy (RTRT) system, the
      SyncTraX FX4 (Shimadzu, Kyoto, Japan), consisting of four X-ray tubes and four
      ceiling-mounted flat panel detectors (FPDs) combined with a linear accelerator,
      was installed at Uonuma Kikan Hospital (Niigata, Japan) for the first time
      worldwide. In addition to RTRT, the SyncTraX FX4 system enables bony structure
      based patient verification. Here we provide the first report of this system's
      clinical commissioning for intracranial stereotactic radiotherapy (SRT).
      MATERIALS & METHODS: A total of five tests were performed for the commissioning:
      evaluations of (1) the system's image quality; (2) the imaging and treatment
      coordinate coincidence; and (3) the localization accuracy of cone-beam computed
      tomography (CBCT) and SyncTraX FX4; (4) the measurement of air kerma; (5) an end
      to-end test. RESULTS & DISCUSSION: The tests revealed the following. (1) All
      image quality evaluation items satisfied each acceptable criterion in all FPDs.
      (2) The maximum offsets among the centers were <=0.40 mm in all combinations of
      the FPD and X-ray tubes (preset). (3) The isocenter localization discrepancies
      between CBCT and preset #3 in the SyncTraX FX4 system were 0.29 +/- 0.084 mm for
      anterior-posterior, -0.19 +/- 0.13 mm for superior-inferior, 0.076 +/- 0.11 mm
      for left-right, -0.11 +/- 0.066 degrees  for rotation, -0.14 +/- 0.064 degrees 
      for pitch, and 0.072+/-0.058 degrees  for roll direction. the Pearson's product
      moment correlation coefficient between the two systems was >0.98 in all
      directions. (4) The mean air kerma value for preset #3 was 0.11 +/- 0.0002 mGy in
      predefined settings (80 kV, 200 mA, 50 msec). (5) For 16 combinations of gantry
      and couch angles, median offset value in all presets was 0.31 mm (range 0.14-0.57
      mm). CONCLUSION: Our results demonstrate a competent performance of the SyncTraX
      FX4 system in terms of the localization accuracy for intracranial SRT.

PMID- 30273445
TI  - YoungMito 2018: Report on the 1st International Mitochondria Meeting for Young
      Scientists.
AB  - The 1st International Mitochondria Meeting for Young Scientists (International
      YoungMito 2018) was held at Hotel Co-op Inn Kyoto in Kyoto, Japan, from 20 to 22
      April 2018. The meeting was attended by 130 mitochondrial researchers from 15
      countries. International YoungMito 2018 was the first international mitochondria
      meeting held in Japan organized by and for young mitochondrial researchers. Over
      the 3-day period, there were 28 oral presentations including two keynote
      lectures, 20 presentations from invited speakers, and six short talks selected
      from abstract submissions. Many different topics were covered including quality
      control pathways acting against mitochondrial stresses, mitochondrial dynamics,
      protein/lipid transport, cristae organization, respiration/ATP synthesis, mtDNA
      maintenance, mitochondrial disease models, and pharmacological approaches. In
      addition, we had 64 posters, a number which represented almost half of all
      attendees. Thanks to the cutting-edge information and high-quality unpublished
      data that were presented, there were many lively discussions during oral and
      poster sessions that continued into the coffee breaks, lunchtime, and nighttime
      discussions. The 1st international YoungMito meeting was successful in promoting
      intellectual exchange among all participants, facilitating collaborations beyond
      national boundaries, and closed with great success. It was a great pleasure that
      many participants were looking forward to the next YoungMito meeting.

PMID- 30273446
TI  - A Cyclometalated N-Heterocyclic Carbene: The Wings of the First Pt2 (II,II)
      Butterfly Oxidized by CHI3.
AB  - The X-ray study on a single crystal of the butterfly-like complex [{Pt(C^C*)(MU
      pz)}2 ] (1), containing a cyclometalated N-heterocyclic carbene ligand as wings
      (HC^C*=1-(4-(ethoxycarbonyl)phenyl)-3-methyl-1H-imidazol-2-ylidene), showed three
      molecules in the asymmetric unit with intermetallic separations (A) of 3.2294(4)
      (1A), 3.2834(4) (1B), and 3.1208(6) (1C). From the reaction of 1 with excess of
      CHI3 in the air and the sunlight, complex [{Pt(C^C*)(MU-pz)I)}2 ] (2) (dPt-Pt
      =2.6079(2) A) was obtained as the major product, while [IPt(C^C*)(MU-pz)2
      Pt(C^C*)CHI2 ] (3) (dPt-Pt =2.6324(3) A) was obtained as the major product under
      argon atmosphere in the dark. Experimental and theoretical investigations showed
      that an easily accessible radical-like mechanism operates under thermal
      conditions, with dioxygen acting as an efficient radical (R. ) scavenger. The
      oxidation of a Pt2 (II,II) "butterfly" by CHI3 to give metal-metal bonded Pt2
      (III,III) compounds is described now for the first time.

PMID- 30273447
TI  - Rostro-caudal organization of the human posterior superior temporal sulcus
      revealed by connectivity profiles.
AB  - The posterior superior temporal sulcus (pSTS) plays an important role in
      biological motion perception but is also thought to be essential for speech and
      facial processing. However, although there are many previous investigations of
      distinct functional modules within the pSTS, the functional organization of the
      pSTS in its full functional heterogeneity has not yet been established. Here we
      applied a connectivity-based parcellation strategy to delineate the human pSTS
      subregions based on distinct anatomical connectivity profiles and divided it into
      rostral and caudal subregions using diffusion tensor imaging. Subsequent
      multimodal connection pattern analyses revealed distinct subregional connectivity
      profiles. From this we inferred that the two subregions are involved in distinct
      functional circuits, the language processing loop and the cognition attention
      network. These results indicate a convergent functional architecture of the pSTS
      that can be revealed based on different types of connectivity and is reflected in
      different functions and interactions. In addition, when the subregions were
      performing their processing in the different functional circuits, we found
      asymmetry in the bilateral pSTS. Our findings may improve the understanding of
      the functional organization of the pSTS and provide new insights into its
      interactions and integration of information at the subregional level.

PMID- 30273448
TI  - Focal application of accelerated iTBS results in global changes in graph
      measures.
AB  - Graph analysis was used to study the effects of accelerated intermittent theta
      burst stimulation (aiTBS) on the brain's network topology in medication-resistant
      depressed patients. Anatomical and resting-state functional MRI (rs-fMRI) was
      recorded at baseline and after sham and verum stimulation. Depression severity
      was assessed using the Hamilton Depression Rating Scale (HDRS). Using various
      graph measures, the different effects of sham and verum aiTBS were calculated. It
      was also investigated whether changes in graph measures were correlated to
      clinical responses. Furthermore, by correlating baseline graph measures with the
      changes in HDRS in terms of percentage, the potential of graph measures as
      biomarker was studied. Although no differences were observed between the effects
      of verum and sham stimulation on whole-brain graph measures and changes in graph
      measures did not correlate with clinical response, the baseline values of
      clustering coefficient and global efficiency showed to be predictive of the
      clinical response to verum aiTBS. Nodal effects were found throughout the whole
      brain. The distribution of these effects could not be linked to the strength of
      the functional connectivity between the stimulation site and the node. This study
      showed that the effects of aiTBS on graph measures distribute beyond the actual
      stimulation site. However, additional research into the complex interactions
      between different areas in the brain is necessary to understand the effects of
      aiTBS in more detail.

PMID- 30273450
TI  - Visual Exploration in Autism Spectrum Disorder: Exploring Age Differences and
      Dynamic Features Using Recurrence Quantification Analysis.
AB  - Eye-tracking studies have demonstrated that individuals with autism spectrum
      disorder sometimes show differences in attention and gaze patterns. This includes
      preference for certain nonsocial objects, heightened attention to detail, and
      more difficulty with attention shifting and disengagement, which may be
      associated with restricted and repetitive behaviors. This study utilized a visual
      exploration task and replicates findings of reduced number of objects explored
      and increased fixation duration on high autism interest objects in a large sample
      of individuals with autism spectrum disorder (n = 129, age 6-54 years) in
      comparison with a typically developing group. These findings correlated with
      parent-reported repetitive behaviors. Additionally, we applied recurrent
      quantification analysis to enable identification of new eye-tracking features,
      which accounted for temporal and spatial differences in viewing patterns. These
      new features were found to discriminate between autism spectrum disorder and
      typically developing groups and were correlated with parent-reported repetitive
      behaviors. Original and novel eye-tracking features identified by recurrent
      quantification analysis differed in their relationships to reported behaviors and
      were dependent on age. Trial Registration: NCT02299700. Autism Research 2018, 11:
      1554-1566. (c) 2018 International Society for Autism Research, Wiley Periodicals,
      Inc. LAY SUMMARY: Using eye-tracking technology and a visual exploration task, we
      showed that people with autism spectrum disorder (ASD) spend more time looking at
      particular kinds of objects, like trains and clocks, and look at fewer objects
      overall than people without ASD. Where people look and the order in which they
      look at objects were related to the restricted and repetitive behaviors reported
      by parents. Eye-tracking may be a useful addition to parent reports for measuring
      changes in behavior in individuals with ASD.

PMID- 30273451
TI  - Zinc Oxide-Catalyzed Dehydrogenation of Primary Alcohols into Carboxylic Acids.
AB  - Zinc oxide has been developed as a catalyst for the dehydrogenation of primary
      alcohols into carboxylic acids and hydrogen gas. The reaction is performed in
      mesitylene solution in the presence of potassium hydroxide, followed by workup
      with hydrochloric acid. The transformation can be applied to both benzylic and
      aliphatic primary alcohols and the catalytically active species was shown to be a
      homogeneous compound by a hot filtration test. Dialkylzinc and strongly basic
      zinc salts also catalyze the dehydrogenation with similar results. The mechanism
      is believed to involve the formation of a zinc alkoxide which degrades into the
      aldehyde and a zinc hydride. The latter reacts with the alcohol to form hydrogen
      gas and regenerate the zinc alkoxide. The degradation of a zinc alkoxide into the
      aldehyde upon heating was confirmed experimentally. The aldehyde can then undergo
      a Cannizzaro reaction or a Tishchenko reaction, which in the presence of
      hydroxide leads to the carboxylic acid.

PMID- 30273452
TI  - [ESTABLISHMENT OF ENDOCRINE SURGERY IN UKRAINE. KHARKOV'S SCHOOL OF ENDOCRINE
      SURGEONS].

PMID- 30273453
TI  - [OPTIMIZATION OF TREATMENT OF THE PATIENTS, SUFFERING NEUROPATHICALLY-INFECTED
      FORM OF THE DIABETIC FOOT SYNDROME, USING THE IODINE PREPARATIONS AND LOW
      INTENSIVE LASER IRRADIATION].
AB  - The changes in antibiotic sensitivity of the purulent-necrotic processes agents
      under the low-intensive laser irradiation impact were studied in experimental
      part of the investigation. There were 156 patients, suffering neuropathically
      infected form of the diabetic foot syndrome, examined and treated, in 41 of them
      the iodine deficiency was revealed. Durable regional intaarterial infusion, low
      intensive laser irradiation and preparations of iodine in a daily dose of 200 mcg
      were applied. High efficacy of the antibacterial therapy photomodification was
      proved, it have permitted to improve the results of treatment, to refuse from
      disabling operations in majority of the patients, to secure the foot bearing
      function. While the iodine deficiency presence the results of treatment are
      improved due to application of the iodine preparations.

PMID- 30273454
TI  - [CLINICO-MORPHOLOGICAL SUBSTANTIATION OF THE LAPAROSCOPIC INTERVENTIONS
      ADVANTAGES, USING ARGON-PLASM COAGULATION IN THE TREATMENT OF HEPATIC
      HEMANGIOMA].
AB  - The clinic-morphological investigation on the efficacy results while application
      of the argon-plasm coagulation (APC) in combination with laparoscopy in the
      treatment of hepatic hemangioma, are presented. The conduction of laparoscopic
      intervention, using the APC, have promoted the improvement of postoperative
      rehabilitation in the patients in aspects of subjective (the pain intensity) and
      clinic-laboratory indices of hepatic function. In accordance to the morphological
      investigation data, based on hepatic biopsies, more organ-preserving impact of
      the APC was noted on hepatic parenchyma.

PMID- 30273455
TI  - [THE CONTENTS OF FORMATION OF THE ELECTRIC WELDING ANASTOMOSIS OF STOMACH AND
      SMALL INTESTINE].
AB  - The character and sequence of changes in the tissues structure of the
      gastrointestinal walls under the impact of the impulse and constant delivery of
      electric pressure with frequency 440 kHz were studied. The investigation object
      was squeezed, using the force, measured from 2 to 6 N/mm2. The EKVZE-300
      "Patonmed" apparatus was used as a source of supply. Electric parameters of the
      process was fixed, using the analogue-numerical digital converter LCard E20-10
      and laboratory oscilloscope Tektronix TDS 3014C. There was established, that
      electric conjunction of stomach and small intestine include three elements:
      destroying and disappearance of mucosa, connective tissue and membranes; fusion
      of the collagen fascicles and the smooth muscle cells; the loss of the collagen
      fascicles and the smooth muscle structure and creation of homogenous electric
      welding suture. The first two elements of the electric welding anastomosis are
      occurring simultaneously, but not dependent one from the other. At the welding
      suture completion the nondestructive changes of the tissues are spreading on a
      distance not more than 1 mm beyond the borders of the electrods apposition.

PMID- 30273456
TI  - [IMPACT OF THE TISSUES OEDEMA ON THE RESULT OF SURGICAL TREATMENT OF
      INFLAMMATION].
AB  - Significance of the tissues oedema and its elimination in the course of
      inflammation and the wound healing was investigated. There were analyzed the
      results of treatment of 68 patients, suffering inflammatory and necrotic
      affection of soft tissues, including 65 - a lower one, 3 - an upper. In 47
      observations the affection course was an acute, while in 18 - chronic. In 36
      patients (control group) a local and systemic antibacterial therapy were
      conducted, and in accordance to indications - surgical interventions; in 32 (main
      group) this treatment was added with tight bandaging of the extremity, using
      elastic bandage. Tight squeezing of tissues with the oedema elimination on
      background of an adequate antibacterial therapy and surgical sanation of purulent
      necrotic focus is accompanied by arrest of infiltrative and exudative stages of
      an acute inflammation, promotes an active course of the inflammation
      proliferative stage. While treatment of chronic cutaneous defect, the application
      of tight squeezing have promoted the granulating shaft resolution, the
      granulation growth in the wound and its boundary epithelization.

PMID- 30273457
TI  - [POSSIBILITIES OF THE FORCED INTRAARTERIAL INJECTION OF MEDICINAL PREPARATIONS IN
      A COMPLEX OF TREATMENT FOR THE LOWER EXTREMITIES CHRONIC ISCHEMIA].
AB  - The efficacy and prognostic significance of the forced intraarterial injection of
      medicinal preparations in complex of treatment in patients, suffering chronic
      ischemia of the lower extremities tissues, was studied. In experimental
      conditions of the main blood flow blockade the forced intraarterial injection of
      medicinal preparations have promoted the release of vessels from cellular
      aggregates and the blood clots; and in the ischemia of degree II - IIIa - has
      determined more pronounced clinical improvement. Appearance of reactive hyperemia
      of the foot in terms more than 2 min have witnessed the hopelessness of the
      extremity saving.

PMID- 30273458
TI  - [MORPHOLOGY OF THE DIABETIC FOOT SYNDROME].
AB  - Local morphological changes were studied in dynamics in 215 patients, suffering
      diabetic foot syndrome. While an adequate local treatment conduction, in
      accordance to the standards elaborated, the histological investigations data have
      shown the oedema, the cellular infiltration and microcirculatory disorders
      reduction in the wound boundary zone. In 1 week of treatment in biopsies a young
      granulating tissue was observed, consisting of big quantity of vascular loops,
      oriented perpendicularly towards the wound surface and multiple bundles of
      fibroblasts. In a period of 2 weeks an active multilayered wound defect
      epithelization was seen. The stratum creeps, right from the skin secured,
      covering the wound surface.

PMID- 30273459
TI  - [ARTERIAL PRESSURE ON THE FIRST TOE AS A PROGNOSIS CRITERION OF THE COMPLICATION
      OCCURRENCE IN THE DIABETIC FOOT SYNDROME ON BACKGROUND OF MENKEBERG'S SCLEROSIS].
AB  - In the patients, suffering diabetes mellitus type II, treated in 2015 - 2016 yrs
      for complicated diabetic foot syndrome, a systolic arterial pressure (SAP) on
      level of the first toe was determined, and roentgenography of the foot in two
      projections done. The SAP value from 120 to 200 mm Hg and higher have had witness
      the presence of Menkeberg?s sclerosis stages III - V. Prognostically favorable is
      a SAP value of 80 mm Hg and higher, and unfavorable data - the SAP value lowering
      lesser than 80 mm Hg. The SAP value lower than 30 mm Hg have had witness the
      vessel obliteration and thrombosis occurrence.

PMID- 30273460
TI  - [THE ELECTRICAL CONDUCTIVITY OF THE TISSUE IN THE EXPERIMENT AS A MODERN METHOD
      OF VIABILITY SCALPED LIMB INJURIES DIAGNOSTIC].
AB  - In experimental research the method for determining of viability of tissue and
      device for its realization were developed to improve treatment results degloving
      injuries of limbs.

PMID- 30273461
TI  - [EVOLUTION OF VIEWS CONCERNING TREATMENT OF PANCREONECROSIS].

PMID- 30273462
TI  - [TRANSHEPATIC FRAME-LIKE EXTERNAL-INTERNAL DRAINAGE OF BILIARY DUCTS FOR
      OBTURATION JAUNDICE].

PMID- 30273465
TI  - [DIAGNOSTIC AND PROGNOSTIC UTILITY OF ENTERAL FAILURE IN PATIENTS WITH ACUTE
      NECROTIC PANCREATITIS].
AB  - Acute necrotic pancreatitis was followed by disorders of intestinal functions in
      96.7% of patients and in 68% - its failure was occurred what had directly
      influenced on frequency of purulent-septic complication and mortality rate. It
      was proved that citrulline plasma level had been objectively reflected the
      severity of enteral failure and served as independent lethality criteria in
      patients with acute necrotic pancreatitis.

PMID- 30273466
TI  - [LIFTING LAPAROSCOPY IN SIMULTANT SURGERY].
AB  - Results of treatment of 84 patients, to whom simultant operative interventions on
      abdominal, the small pelvis and retroperitoneal organs were performed for
      concomitant somatic diseases, were analyzed. The author's technology of
      laparolifting was applied in 36 patients, and classical technology with
      carboxyperitoneum adjustment - in 48. Variants of optimal operative accesses were
      determined, structure and rate of postoperative complications, peculiarities of
      the early postoperative period course studied. Indisputable advantages of the
      lifting laparoscopic operations were established, including reduction of the
      postoperative complications rate and severity, the postoperative pain syndrome
      intensity, the concurrent chronic diseases exacerbation rate, and postoperative
      stationary stay.

PMID- 30273467
TI  - [DIAGNOSIS AND TREATMENT OF ESOPHAGEAL INJURY].
AB  - Results of diagnosis and treatment of 19 injured persons, suffering esophageal
      damage of various etiology, were analyzed.Peculiarities of clinical signs and
      diagnosis of esophageal injury on various levels and complications were
      investigated. Various methods of the injured persons' treatment, concerning the
      damage character, terms of appeal for medical care, presence of complications and
      concurrent diseases, were adduced. Optimal ways of treatment for the injured
      persons, suffering esophageal damage, were proposed.

PMID- 30273468
TI  - [ESTIMATION OF FORMATION OF HEPATICOJEJUNOANASTOMOSES, USING METHOD OF THE HF
      ELECTRIC WELDING OF BIOLOGICAL TISSUES].
AB  - Hepaticojejunoanastomosis (HJA), using the HF-electric welding method, was
      formatted in 14 patients, suffering the bile outflow disorders along main biliary
      ducts, in 6 of them - with a common hepatic duct stricture, the HJA stricture,
      purulent cholangitis, iatrogenic injury of biliary ducts, and in 8 - with
      malignant tumours of periampullary zone. In all the patients the welding averting
      one-layer termino-lateral or latero-lateral HJA were formatted. Welding
      anastomoses were hermetic, quite hard, immediately after formation and so on.
      Comparative analysis of clinic-laboratory postoperative indices has confirmed the
      best results achievement of the method proposed.

PMID- 30273469
TI  - [RESULTS OF THE TOTAL CAVA-PULMONARY CONNECTION PROCEDURE WITH CORRECTION OF
      ATRIO-VENTRICULAR VALVES IN PATIENTS OF DIFFERENT AGE, SUFFERING SINGLE CARDIAC
      VENTRICULUS].
AB  - The investigation objective was to improve the patients' management, suffering a
      single cardiac ventriculus, in whom a total cava-pulmonary connection (TSRS)
      operation was performed together with correction of the atrio-ventricular valves
      (AVV) insufficiency, basing on analysis of immediate and middle-term results.
      From 2005 to 2015 yrs in the clinic the TSRS operation was performed in 132
      patients. Of them 24 patients were choosed , in whom moderate and pronounced
      insufficiency of systemic AVV was diagnosed. Good early and middle-term results
      were achieved in 92% patients. In 8 observations, while the AVV correcting, in
      every patient two and more procedures of plasty were applied. Complex approach,
      using combination of various procedures of plasty, has guaranteed the optimal
      result. Application of procedures for the fiber ring stabilization have promoted
      achievement of best results.

PMID- 30273470
TI  - [RESULTS OF TREATMENT IN PATIENTS, SUFFERING STENOSIS OF CAROTID ARTERIES IN
      COMBINATION WITH DISEASES OF OTHER SYSTEMS].
AB  - Results of treatment in 2010 - 2015 yrs of 187 patients, suffering
      haemodynamically significant stenosis of carotid arteries, on background of
      upcoming surgical treatment of the lower extremities tissues chronic ischemia, an
      ischemic heart disease or diseases of digestive system, were analyzed. In
      generalized atherosclerosis and an acute disorder of the brain blood circulation
      in anamnesis it is necessary to conduct the carotid arteries affection screening.
      In haemodynamically significant stenosis of carotid arteries in patients,
      suffering an ischemic heart disease and the digestive system diseases, as a first
      stage a carotid endarterectomy was performed for reduction of the occurrence risk
      for ischemic insult after operation performed for the main disease.

PMID- 30273471
TI  - [PROPHYLAXIS OF COGNITIVE DEFICIENCY WHILE PERFORMING ENDARTERECTOMY IN PATIENTS,
      SUFFERING STENOTIC AFFECTIONS OF CAROTID ARTERIES: THE ROLE OF MULTIDISCIPLINARY
      APPROACH].
AB  - Efficacy of the cognitive deficiency prophylaxis was studied in patients,
      suffering stenotic affection of carotid arteries. Application of intraoperative
      neuroprotection, using neoton, have permitted to reduce the reperfusion syndrome
      signs rate from 35.6 to 3.4%, and the cognitive deficiency level as well, causing
      the general occurrence risk of intraoperative or early morbidity lowering. It is
      expedient to apply the multidisciplinary approach for guaranteeing of adequate
      quality of clinical monitoring for cognitive functions.

PMID- 30273472
TI  - [SURGICAL TREATMENT OF PATIENTS FOR METACHRONOUS METASTASES OF PULMONARY
      OSTEOSARCOMA. CLINICAL PROGNOSTIC FACTORS].
AB  - The impact of surgical method on results of complex treatment in patients,
      suffering the osteosarcoma metachronous pulmonary metastases, was studied. The
      survival indices in 93 patients were analyzed, of them in 71, suffering
      osteosarcoma - with complex treatment, including surgical intervention of
      complete excision of all metastases (three-years survival - 34.2%), and in 21 -
      complex treatment with palliative radiation therapy (three-year survival 3.7%).
      Trustworthy impact on three-years survival indices was proved for such clinical
      factors, as the terms of the metastases occurrence (6 mo and lesser, and more,
      than 6 mo) and quantity of metastases (up to 5, 5 and more) present.

PMID- 30273473
TI  - [STANDARD TRANSCUTANEOUS AND ULTRA-MINI TRANSCUTANEOUS NEPHROLITHOTRIPSY IN
      TREATMENT OF NEPHROLITHIASIS].
AB  - Comparative analysis of two variants of transcutaneous nephrolithotripsy (TCNLT)
      in 45 patients, suffering nephrolithiasis, was performed. In 17 patients (the
      first group) the ultra-mini (UM) TCNLT, using tubus 11Sh, was done, and in 28
      patients (the second group) - TCNLT, using a standard tubus 24Sh. The operation
      duration in the first group have had constituted (86.2 +/- 16.3) min at average,
      and in the second group - (51 +/- 13.6) min. The method of UM TCNLT is a secure,
      miniinvasive, owing low rate of morbidity, comparing with a standard procedure,
      but with equal efficacy, concerning the "stone free" status (accordingly, 95.3
      and 96.5%) in patients when calculi's diameter up to 2 sm. Tubus 11Ch guarantees
      lesser risk of hemorrhagic complications occurrence, permits to conduct UM TCNLT
      without nephrostomic draining of the renal calyx and pelvis system more
      confidently.

PMID- 30273474
TI  - [TRAUMAGENESIS, EPIDEMIOLOGICAL AND NOSOLOGICAL CHARACTERISTICS OF THE GUN-SHOT
      EXPLOSIVE WOUNDINGS OF THE PEACE TIME IN CHILDREN].
AB  - Structure of the gun-shot-explosive woundings (GSEW) of the peacetime, occurred
      in 35 children, was analyzed with refinement, concerning a weapon kind and motif
      of application, as well as clinic-epidemiological and clinic-nosological
      characteristics of injuries. Analysis of the data was conducted in accordance to
      criteria and demands of evidence-based medicine, using the methods of
      nonparametric statistics and computeric technologies. Clinic-epidemiological
      characteristic of the wounded persons have had witnessed, that due to the GSEW
      accidents suffer children, ageing (11.97 +/- 0.68) yrs, mainly boys. The main
      causes of GSEW were: careless handling of weapons - in 52.6% observations,
      hooligan's actions - in 28.9%. Clinical peculiarities of a peacetime GSEW in
      children have had depended upon the injury severity, caused by special kind of
      traumatic weapon and traumatic missiles applied.

PMID- 30273476
TI  - [THE PROVISION OF MODERN ASPECTS OF SURGICAL ADD TO WOUNDED PERSONS FOR THE
      BRACHIAL BONE GUN-SHOT FRACTURE].
AB  - The complex of operative interventions on all levels of medical add was analyzed
      in 57 wounded persons, treated for the brachial bone gun-shot fracture and for
      the extremity affection on the humerus level in 2014 - 2015 yrs period. Primary
      and repeated surgical processing of the wounds was done in 94.7% wounded persons,
      the core apparatuses of external fixation were imposed in 85.9%. Vacuum-therapy
      was conducted in 17.5% wounded persons, free autodermoplasty and autovenous
      prosthesis of artery was accomplished in 10.5%. Good functional results were
      achieved in 47.4% wounded persons, satisfactory - in 40.3%, bad - in 12.3%. The
      management and treatment-diagnostic faults were analyzed.

PMID- 30273478
TI  - [CHANGES OF PH AND CYTOLOGICAL PICTURE AT VARIOUS STAGES OF WOUND HEALING IN
      PATIENTS WITH VENOUS GENESIS TROPHIC ULCERS OF THE LOWER LIMBS].
AB  - The analysis of 82 patients medical records with venous trophic ulcers (VTU) of
      the lower limbs were presenting. pH in patients with VTU determined in three
      locations: the surface of ulcers, venous modified and unmodified skin and ulcers.
      Cytological examination of secretions from wounds conducted in 32 (39.1%)
      patients using smears. In 19 (23.2%) patients prevailed exudation stage, in 37
      (45.1%) - granulation, in 26 (31.7%) - epithelialization. At all stages of wound
      healing at a distance from the ulcers observed values change skin pH to the acid
      side. Typical sings of first phase of wound healing were degenerative
      inflammatory and inflammatory type of cytogram, and for the granulation phase -
      inflammatory-regenerative and regenerative one.

PMID- 30273477
TI  - [APPLICATION OF VACUUM-THERAPY IN COMPLEX OF TREATMENT OF THE LOWER EXTREMITIES
      CHRONIC WOUNDS].
AB  - Experience of treatment of chronic wounds in 11 patients in 2014 - 2016 yrs was
      analyzed. The impact of negative pressure, using domestically manufactured
      apparatus "AGAT- Dnepr", in complex of treatment as a local therapy, was applied.
      Vacuum-therapy was conducted preoperatively and postoperatively together with
      autodermoplasty. The injection material for the skin regeneration "lacerta" was
      applied subcutaneously intraoperatively. The Ialuset-cream bandages were used in
      10 - 12 days postoperatively during 2-3 weeks. Efficacy of vacuum-therapy was
      estimated, basing on analysis of the wound process course dynamics, clinic
      laboratory criteria, terms of the wound defect complete closure. The patients'
      stationary treatment duration have constituted 38.3 days at average. Complex
      treatment of chronic wounds have had guaranteed complete healing of the wound
      defect in 7 (63%) patients in terms up to 1 - 5 weeks, and in 3 (26%) - 6 weeks.

PMID- 30273480
TI  - Antibacterial Surface Coating for Bone Scaffolds Based on the Dark Catalytic
      Effect of Titanium Dioxide.
AB  - Biomaterials which promote tissue integration and resist microbial colonisation
      are required in bone tissue engineering to prevent biomaterial-associated
      infections. Surface modification of established materials for bone tissue
      engineering, such as TiO2, have emerged as promising anti-infective strategies.
      Interestingly, the antibacterial activity of TiO2 in the form of particles can be
      enhanced by combining it with H2O2, even in the absence of irradiation. However,
      it remains unknown whether TiO2 surfaces elicit a similar effect. In this study,
      the antibacterial effect of porous TiO2 scaffolds generated by the catalytic
      decomposition of H2O2 in the absence of light (dark catalysis) was investigated.
      Porous ceramic foams were fabricated and sol-gel coated for high catalytic
      activity. Degradation of methylene blue in the presence of 3% H2O2 increased by
      80% for the sol-gel-coated surfaces. The degradation kinetics indicate that
      intermediate free radicals that form at the liquid-TiO2 interface are responsible
      for the oxidative behavior of the surface. TiO2 surfaces were further pretreated
      with 30% H2O2 for prolonged oxidative behavior. The biological response toward
      such surfaces was assessed in vitro. S. epidermidis biofilms formed on modified
      surfaces showed reduced viability compared to nonmodified surfaces. Further, the
      same surface modification showed no cytotoxic effects on MC3T3 preosteoblasts.
      However, the results from the conducted genotoxicity assay were inconclusive, and
      further studies are needed to exclude ROS-mediated DNA damage. To conclude, this
      study provides evidence that a simple surface modification based on the dark
      catalytic effect of TiO2 can be used to create antibacterial surface properties
      for ceramic bone scaffolds.

PMID- 30273479
TI  - [THE IMPACT OF XENOTRANSPLANTATION OF NEUROGENIC STEM CELLS IN COMPLEX WITH THE
      TISSUE MATRIX NEUROGELTM ON THE POSTTRAUMATIC SPASTICITY SYNDROME COURSE IN
      EXPERIMENT].
AB  - The impact of implantation of synthetic matrix NeuroGelTM together with
      neurogenic stem cells (NSC) on the course of posttraumatic spasticity syndrome
      was studied. The laboratory animals were white mongrel male rats (5 mo, 250 g);
      the trauma simulation - transsection of the left half of spinal cord (SC) on the
      TXI level. Experimental group 1 consisted of a SC trauma, homotopic implantation
      of NeuroGelTM together with NSC of fetal (E17) mice hippocampus (n=20); while
      group 2 - a SC trauma, homotopic implantation of NeuroGelTM (n=20); and group 3 -
      a SC trauma (n=16). Investigation of the function index and the spasticity index
      of posterior ipsilateral extremity was done in accordance to Basso-Beattie
      Bresnahan and Ashworth scales. Association of the function index and the
      spasticity index of posterior ipsilateral extremity in all groups in various
      variants of the samples formation is ambiguous, witnessing possibility of
      additional correlation between these characteristics of a movement system. The
      NSC xenotransplantation in conjunction with NeuroGelTM changes the spasticity
      syndrome course, creates conditions for its facilitation in remote period after a
      SC trauma.

PMID- 30273481
TI  - Superhydrophobic SiC/CNTs Coatings with Photothermal Deicing and Passive Anti
      Icing Properties.
AB  - For faster and greener anti-icing/deicing, a new generation of anti-icing
      materials are expected to possess both passive anti-icing properties and active
      deicing properties. The photothermal effect of carbon nanotubes (CNTs) is used in
      the field of photothermal cancer therapy, while the application in anti
      icing/deicing is seldom investigated. Superhydrophobic SiC/CNTs coatings with
      photothermal deicing and passive anti-icing properties were first prepared by a
      simple spray-coating method. The results of 3D profile and microstructure
      observed via scanning electron microscopy demonstrate that the micronanostructure
      combined with peaklike SiC microstructure and villiform CNTs nanostructure makes
      the coatings surface superhydrophobic, exhibiting a water contact angle of up to
      161 degrees  and a roll angle as low as 2 degrees . This micronanostructure can
      also reduce ice anchoring and ice adhesion strength. Utilizing the photothermal
      effect of CNTs, the surface temperature of the coatings is rapidly increased upon
      near-infrared light (808 nm) irradiation. The heat is transferred rapidly to the
      surroundings by highly thermal conductive CNTs. The light-to-heat conversion
      efficiency in deicing tests is approximately 50.94%, achieving a highly efficient
      remote deicing effect. This superhydrophobic coating combining photothermal
      deicing and passive anti-icing properties is expected to be further used in
      various practical applications and in development of a new generation of anti
      icing/deicing coatings.

PMID- 30273483
TI  - Building Block Based Construction of Membrane-Organelle Double Targeted
      Nanosystem for Two-Drug Delivery.
AB  - Despite the claim that encapsulation of drugs improves the therapeutic profile of
      free drugs, there are still important limitations in drug delivery. With respect
      to cancer treatment, two promising implementations are combination therapy and
      targeted devices, which are aimed at increasing the drug effect either by
      achieving higher cell death rates or by discriminating between cell populations.
      However, for the time being, the scope of combining both approaches is unknown.
      To advance this knowledge, a two-drug-delivery system with dual cell-organelle
      targeting based on mesoporous silica nanoparticles, which are known to be able to
      host drugs within their pores, has been designed. In vitro results show a
      synergistic effect and high efficacy, demonstrating that the combination of dual
      therapy and targeting could still advance the development of drug-delivery
      nanodevices against difficult-to-treat cancers.

PMID- 30273482
TI  - Phosphorylation Alters the Residual Structure and Interactions of the Regulatory
      L1 Linker Connecting NBD1 to the Membrane-Bound Domain in SUR2B.
AB  - ATP-sensitive potassium (KATP) channels in vascular smooth muscle are comprised
      of four pore-forming Kir6.1 subunits and four copies of the sulfonylurea receptor
      2B (SUR2B), which acts as a regulator of channel gating. Recent electron cryo
      microscopy (cryo-EM) structures of the pancreatic KATP channel show a central
      Kir6.2 pore that is surrounded by the SUR1 subunits. Mutations in the L1 linker
      connecting the first membrane-spanning domain and the first nucleotide binding
      domain (NBD1) in SUR2B cause cardiac disease; however, this part of the protein
      is not resolved in the cryo-EM structures. Phosphorylation of the L1 linker, by
      protein kinase A, disrupts its interactions with NBD1, which increases the MgATP
      affinity of NBD1 and KATP channel gating. To elucidate the mode by which the L1
      linker regulates KATP channels, we have probed the effects of phosphorylation on
      its structure and interactions using nuclear magnetic resonance (NMR)
      spectroscopy and other techniques. We demonstrate that the L1 linker is an
      intrinsically disordered region of SUR2B but possesses residual secondary and
      compact structure, both of which are disrupted with phosphorylation. NMR binding
      studies demonstrate that phosphorylation alters the mode by which the L1 linker
      interacts with NBD1. The data show that L1 linker residues with the greatest
      alpha-helical propensity also form the most stable interaction with NBD1,
      highlighting a hot spot within the L1 linker. This hot spot is the site of
      disease-causing mutations and is associated with other processes that regulate
      KATP channel gating. These data provide insights into the mode by which the
      phospho-regulatory L1 linker regulates KATP channels.

PMID- 30273484
TI  - Nitrogen and Phosphorus Codoped Porous Carbon Framework as Anode Material for
      High Rate Lithium-Ion Batteries.
AB  - Slow kinetics and low specific capacity of graphite anode significantly limit its
      applications in the rapidly developing lithium-ion battery (LIB) markets. Herein,
      we report a carbon framework anode with ultrafast rate and cycling stability for
      LIBs by nitrogen and phosphorus doping. The electrode structure is constructed of
      a 3D framework built from 2D heteroatom-doped graphene layers via pyrolysis of
      self-assembled supramolecular aggregates. The synergistic effect from the
      nanostructured 3D framework and chemical doping (i.e., N- and P-doping) enables
      fast kinetics in charge storage and transport. A high reversible capacity of 946
      mAh g-1 is delivered at a current rate of 0.5 A g-1, and excellent rate
      capability (e.g., a capacity of 595 mAh g-1 at 10 A g-1) of the electrode is
      shown. Moreover, a moderate surface area from the 3D porous structure contributes
      to a relatively high initial Coulombic efficiency of 74%, compared to other
      graphene-based anode materials. The electrode also demonstrates excellent cycling
      stability at a current rate of 2 A g-1 for 2000 cycles. The synthetic strategy
      proposed here is highly efficient and green, which can provide guidance for large
      scale controllable fabrication of carbon-based anode materials.

PMID- 30273485
TI  - Fatty Acid-Based Radically Polymerizable Monomers: From Novel Poly(meth)acrylates
      to Cutting-Edge Properties.
AB  - The increasing price of barrels of oil, global warming, and other environmental
      problems favor the use of renewable resources to replace the petroleum-based
      polymers used in various applications. Recently, fatty acids (FAs) and their
      derivatives have appeared among the most promising candidates to afford novel and
      innovative bio-based (co)polymers because of their ready availability, their low
      toxicity, and their high versatility. However, the current literature mostly
      focused on FA-based polymers prepared by condensation polymerization or
      oxypolymerization, while only a few works have been devoted to radical
      polymerization due to the low reactivity of FAs through radical process. Thus,
      the aim of this Review is to give an overview of (i) the most common synthetic
      pathways reported in the literature to provide suitable monomers from FAs and
      their derivatives for radical polymerization, (ii) the available radical
      processes to afford FA-based (co)polymers, and (iii) the different applications
      in which FA-based (co)polymers have been used since the past few years.

PMID- 30273486
TI  - A Polymer Blend Approach for Creation of Effective Conjugated Polymer Charge
      Transport Pathways.
AB  - Understanding the role of the distribution of polymer chain lengths on process
      structure-property relationships in semiconducting organic electronics has
      remained elusive due to challenges in synthesizing targeted molecular weights (
      Mw) and polydispersity indices. Here, a facile blending approach of various
      poly(3-hexylthiophene) (P3HT) molecular weights is used to investigate the impact
      of the distribution of polymer chain lengths on self-assembly into aggregates and
      associated charge transport properties. Low and high Mw samples were blended to
      form a highly polydisperse sample which was compared to a similar, medium Mw
      control. Self-assembly was induced by preprocessing the polymer solution with UV
      irradiation and subsequent solution aging before deposition via blade-coating.
      Superior charge carrier (hole) mobilities were observed for the blend and control
      samples. Furthermore, their solution lifetimes exceeded 14 days. UV-vis spectral
      analysis suggests that low Mw P3HT lacks the mesoscale crystallinity required for
      percolative charge transport. In contrast, when the Mw is too high, the polymer
      rapidly aggregates, leading to paracrystalline disorder and structural
      inhomogeneity that interrupts charge-transfer pathways. The role of grain
      boundaries, fibrillar order, and macroscale alignment is characterized via
      grazing-incidence wide-angle X-ray scattering, atomic force microscopic, and
      optical microscopic techniques. The results presented here provide additional
      guidance on the interplay between polymer solubility, self-assembly, network
      interconnectivity, and charge transport to enable robust polymer ink formulations
      with reliable and reproducible performance attributes.

PMID- 30273487
TI  - Protein Family-Specific Models Using Deep Neural Networks and Transfer Learning
      Improve Virtual Screening and Highlight the Need for More Data.
AB  - Machine learning has shown enormous potential for computer-aided drug discovery.
      Here we show how modern convolutional neural networks (CNNs) can be applied to
      structure-based virtual screening. We have coupled our densely connected CNN
      (DenseNet) with a transfer learning approach which we use to produce an ensemble
      of protein family-specific models. We conduct an in-depth empirical study and
      provide the first guidelines on the minimum requirements for adopting a protein
      family-specific model. Our method also highlights the need for additional data,
      even in data-rich protein families. Our approach outperforms recent benchmarks on
      the DUD-E data set and an independent test set constructed from the ChEMBL
      database. Using a clustered cross-validation on DUD-E, we achieve an average AUC
      ROC of 0.92 and a 0.5% ROC enrichment factor of 79. This represents an
      improvement in early enrichment of over 75% compared to a recent machine learning
      benchmark. Our results demonstrate that the continued improvements in machine
      learning architecture for computer vision apply to structure-based virtual
      screening.

PMID- 30273488
TI  - Coherences of Bacteriochlorophyll a Uncovered Using 3D-Electronic Spectroscopy.
AB  - Mapping the multidimensional energy landscape of photosynthetic systems is
      crucial for understanding their high efficiencies. Multidimensional coherent
      spectroscopy is well suited to this task but has difficulty distinguishing
      between vibrational and electronic degrees of freedom. In pigment-protein
      complexes, energy differences between vibrations within a single electronic
      manifold are similar to differences between electronic states, leading to
      ambiguous assignments of spectral features and diverging physical
      interpretations. An important control experiment is that of the pigment monomer,
      but previous attempts using multidimensional coherent spectroscopy lacked the
      sensitivity to capture the relevant spectroscopic signatures. Here we apply a
      variety of methods to rapidly acquire 3D electronic-vibrational spectra in
      seconds, leading to a mapping of the vibrational states of Bacteriochlorophyll a
      (BChl a) in solution. Using this information, we can distinguish features of
      proteins containing BChl a from the monomer subunit and show that many of the
      previously reported contentious spectral signatures are vibrations of individual
      pigments.

PMID- 30273489
TI  - Image Correlation Spectroscopy with Second Harmonic Generating Nanoparticles in
      Suspension and in Cells.
AB  - The absence of photobleaching, blinking, and saturation combined with a high
      contrast provides unique advantages of higher-harmonic generating nanoparticles
      over fluorescent probes, allowing for prolonged correlation spectroscopy studies.
      We apply the coherent intensity fluctuation model to study the mobility of second
      harmonic generating nanoparticles. A concise protocol is presented for
      quantifying the diffusion coefficient from a single spectroscopy measurement
      without the need for separate point-spread-function calibrations. The technique's
      applicability is illustrated on nominally 56 nm LiNbO3 nanoparticles. We perform
      label-free raster image correlation spectroscopy imaging in aqueous suspension
      and spatiotemporal image correlation spectroscopy in A549 human lung carcinoma
      cells. In good agreement with the expected theoretical result, the measured
      diffusion coefficient in water at room temperature is (7.5 +/- 0.3) MUm2/s. The
      diffusion coefficient in the cells is more than 103 times lower and
      heterogeneous, with an average of (3.7 +/- 1.5) * 10-3 MUm2/s.

PMID- 30273490
TI  - Interferometric Measurement of Transient Absorption and Refraction Spectra with
      Dual Frequency Comb.
AB  - We demonstrate that a dual frequency comb-transient absorption (DFC-TA) technique
      can be combined with a time-domain interferometric detection to measure both the
      transient absorption and refraction spectra of molecules in solution. To do this,
      the pump-probe signal field of DFC-TA is allowed to interfere with a time-delayed
      local oscillator field in a time domain. We show that this DFC interferometric
      pump-probe spectroscopy (DFC-IPS) technique has a unique ability to extract the
      phase and amplitude information on the pump-probe signal using just a single-scan
      data, while conventional techniques require an independent signal measured
      without the pump field for the normalization of the pump-probe spectrum. As a
      proof-of-principle experiment, we here show that the DFC-IPS enables us to
      simultaneously measure the frequency-resolved (from 650 to 950 nm) transient
      absorption and refraction signals with an exceptionally broad dynamic range from
      femtosecond to nanosecond without using a mechanical translational stage for pump
      probe time-scanning. We anticipate that our DFC-IPS technique with femtosecond
      time-resolution capability will be useful to investigate photoinduced chemical
      and biological reactions covering broad dynamic ranges.

PMID- 30273491
TI  - Tailoring the Tribocorrosion and Antifouling Performance of (Cr, Cu)-GLC Coatings
      for Marine Application.
AB  - Doped graphite-like coating (GLC) has aroused great interest as one of the most
      promising protective materials in marine applications. However, there is a lack
      of systematic research on the tribocorrosion and antifouling performance of doped
      GLC coatings in harsh marine environments. Herein, a multifunctional (Cr, Cu)-GLC
      coating with combined antifouling and tribocorrosion properties was prepared via
      a magnetron sputtering method. The experimental results indicate that the
      resultant coatings changed from a dense structure to a loose columnar structure
      with the increment of Cr and Cu doping amount. At the same time, the hardness of
      the coating gradually decreases, but the contact angle between coating and
      seawater gradually increases. The algae adhesion test reveal that the algae
      density on the surface of the (Cr, Cu)-GLC coating decreases from about 565 to
      70/mm2 as the amount of doping increased. However, on the contrary, the friction
      coefficient of the coating under OCP condition increases from 0.06 to about 0.35.
      Overall, the mild doped (Cr, Cu)-GLC coating exhibits the best comprehensive
      properties, combining antifouling and tribocorrosion properties. The corresponded
      mechanisms are discussed in terms of the coating microstructure, antifouling, and
      tribocorrosion behavior.

PMID- 30273492
TI  - Driving Quick and Large Amplitude Contraction of Viologen-Incorporated Poly-l
      Lysine-Based Hydrogel by Reduction.
AB  - A glutaraldehyde-cross-linked poly-l-lysine-based hydrogel with pendant viologens
      was synthesized with various [viologen unit]/[Lys unit] ratios. The hydrogel with
      the ratio of 25% was extensively characterized. Characterization of the hydrogel
      revealed that (i) water content reaches 95.8%, (ii) unbound viologen unit is
      absent, and (iii) lyophilized gel, showing porous structure, is rewettable. The
      hydrogel in contact with a gold, glassy carbon, pyrolytic graphite, or ITO
      electrode was electroactive, showing voltammetric responses involving diffusion
      process. Occurrence of electron transfer between viologen sites was verified by
      ESR measurements. The electroreflectance spectrum demonstrated significant
      dimerization of one-electron-reduced forms, viologen radical cations. Most
      remarkably, reduction of the hydrogel by dithionite showed a 93% volume decrease,
      being near to the water content, at 100 s and finally 97% contraction at 380 s.
      The initial rate of contraction was 0.02 s-1, and the swelling weight ratio was
      over 17. The contraction rate was much faster than that observed when adding of
      redox-inactive salts in the outer medium. Recovery by reoxidation was relatively
      sluggish even when O2-saturated water was used. The quick and large-amplitude
      contraction with removal of water from the gel body should be the consequence of
      permeability of reductant, interchain pi-stacking of one-electron-reduced forms
      (viologen monoradical monocation), desolvation of viologen upon reduction,
      electron hopping between viologen units and its acceleration with contraction,
      and effective osmotic pressure difference.

PMID- 30273493
TI  - Coenzyme Q10 does not improve peripheral insulin sensitivity in statin-treated
      men and women; the LIFESTAT study.
AB  - Simvastatin is a cholesterol-lowering drug that is prescribed to lower the risk
      of cardiovascular disease following high levels of blood cholesterol. There is a
      possible risk of new onset diabetes mellitus with statin treatment but the
      mechanisms behind are unknown. Coenzyme Q10 (CoQ10) supplementation has been
      found to improve glucose homeostasis in various patient populations and may
      increase muscle GLUT4 content. Our aim was to investigate whether eight weeks of
      CoQ10 supplementation can improve glucose homeostasis in simvastatin treated
      subjects. Thirty-five men and women in treatment with minimum 40 mg of
      simvastatin daily were randomized to receive either 2 x 200 mg/d of CoQ10
      supplementation or placebo for eight weeks. Glucose homeostasis was investigated
      with fasting blood samples, OGTT and IVGTT. Insulin sensitivity was assessed with
      the hyperinsulinemic, euglycemic clamp. Different indices were calculated from
      fasting samples and OGTT as secondary measures of insulin sensitivity. A muscle
      biopsy was obtained from the vastus lateralis muscle for muscle protein analyzes.
      There were no changes in body composition, fasting plasma insulin, fasting plasma
      glucose or 3hr-glucose with intervention, but HbA1c decreased with time. Glucose
      homeostasis measured as the AUC for glucose, insulin and C-peptide during OGTT
      was unchanged after intervention. Insulin secretory capacity was also unaltered
      after CoQ10 supplementation. Insulin sensitivity was unchanged but hepatic
      insulin sensitivity (HOMA2-%S) increased. No changes in muscle GLUT4 content was
      observed after intervention. CoQ10 supplementation does not change muscle GLUT4
      content, insulin sensitivity or secretory capacity, but hepatic insulin
      sensitivity may improve.

PMID- 30273494
TI  - Genetic diversity and symbiotic efficiency difference of endophytic rhizobia of
      Medicago sativa.
AB  - Research on rhizobium diversity has paved the way for diversification of
      rhizobial germplasm resources. Seventy-three endophytic bacterial isolates were
      collected from seven tissues of five alfalfa cultivars in three geographic
      locations in Gansu, China. Restriction fragment length polymorphism (RFLP)
      fingerprinting of 16S rRNA and analysis of concatenated sequence of three
      housekeeping genes (atpD, glnII, and recA) and two symbiotic genes (nodC and
      nifH) were used for strain identification. Results showed that the endophytic
      strains were genetically diverse at different taxonomic levels, and Ensifer
      meliloti (31) and Agrobacterium radiobacter (12) are common Medicago sativa
      endophytic bacteria in Gansu, China. The nifH genes (97%-98% sequence identity)
      of E. meliloti strains were more diverse than the nodC genes (99%-100% sequence
      identity), even though the strains evolved from a common ancestor. The degree of
      dispersion of symbiotic phenotypes of E. meliloti strains on M. sativa 'Gannong
      No. 3', 'Gannong No. 9', and 'Qingshui' was much less than that on M. sativa
      'Longzhong' and 'WL168HQ'. This suggested that the symbiotic efficiency of E.
      meliloti strains on the former three alfalfa cultivars was similar but on the
      latter two was discrepant. Their symbiotic efficiency differed primarily
      according to alfalfa cultivars and, to a lesser extent, to the tested strains,
      indicating the difference in the sensitivity of different alfalfa cultivars to
      rhizobial strains.

PMID- 30273495
TI  - Therapeutic potency of heat-shock protein-70 in the pathogenesis of colorectal
      cancer, current status and perspectives.
AB  - Heat-shock protein-70 (HSP70) is critical to the folding, stability and activity
      of several client proteins including many responsible for cancer cell
      proliferation, apoptosis, drug toxicity, and metastasis. Up-regulation of HSP70
      is positively associated with increased tumorigenicity as well as poor survival
      in colon cancer patients, supporting the diagnostic, prognostic and therapeutic
      potencies of HSP70 in colorectal cancer. Administration of specific
      pharmacological inhibitors or gene knock-down for HSP70 suppresses tumor
      progression and enhances tumor cells chemosensitivity. This review summarizes
      different tumorigenic properties of HSP70 and potential therapeutic potency of
      HSP70 inhibitors as a novel strategy in colorectal cancer therapy for a better
      understanding and hence a better management of this disease.

PMID- 30273496
TI  - Altered driving performance of symptomatic Huntington's disease gene carriers in
      simulated road conditions.
AB  - OBJECTIVE: In clinical practice, patients with Huntington's disease (HD) often
      decide to solely drive in their own familiar neighborhoods and not on a motorway
      or in an unknown area. The aim of the study was to identify differences in
      driving performance between HD gene carriers and healthy individuals in simulated
      urban and motorway environments. METHODS: This cross-sectional study included 87
      participants (28 premanifest HD, 30 manifest HD, 29 controls). All participants
      were active drivers and were assessed using a driving simulator, a driving
      history questionnaire, and the Unified Huntington's Disease Rating Scale. The
      driving simulator session included urban and motorway scenarios. Analysis of
      variance and Kruskal-Wallis tests were used to compare urban and motorway driving
      across all 3 groups. RESULTS: Manifest HD drove slower compared to controls and
      premanifest HD when speed limits increased (80 and 100 km/h) and they had a less
      steady speed compared to premanifest HD on the motorway and in a 30 km/h zone.
      Manifest HD also had a larger standard deviation of the lateral position (i.e.,
      more weaving of the car/less vehicle control) compared to controls and
      premanifest HD on the motorway. CONCLUSIONS: Manifest HD drive more cautious in a
      driving simulator when speed limits increase compared to premanifest HD and
      controls and they have less vehicle control on the motorway. The driving
      simulator parameters are able to discriminate between manifest HD and healthy
      individuals, so a driving simulator seems a feasible tool to use when
      investigating changes in driving in manifest HD.

PMID- 30273498
TI  - Improving Tuberculosis Case Finding in Persons Living with Advanced HIV through
      New Diagnostic Algorithms.

PMID- 30273497
TI  - Sustained Quality Improvement in Outcomes of Preterm Neonates of <29 Weeks'
      Gestational Age: Results from the Evidence-based Practice for Improving Quality
      Phase 3 (EPIQ-3).
AB  - Quality improvement initiatives in neonatology have yielded positive results;
      however, few programs have demonstrated sustainability. We evaluated an ongoing,
      national quality improvement initiative (Evidence-based Practice for Improving
      Quality [EPIQ-3]) on outcomes of preterm neonates 220-286 weeks' gestational age
      (GA). Data from 7459 neonates admitted to 25 Canadian centers between 2013 and
      2017 were studied. Trends in mortality and major morbidities were evaluated. The
      neonates of 220-236 weeks' GA increased from 90 in 2013 to 139 in 2017 without a
      significant change in any other GA categories. In the entire cohort, the odds of
      composite outcome of mortality or any major morbidity (adjusted odds ratio [AOR]
      0.72, 95% confidence interval [CI] 0.61-0.84) and of necrotizing enterocolitis
      (AOR 0.66, 95%CI 0.49-0.89) were lower in 2017 compared to 2013. When calculated
      per year, the odds of composite outcome (AOR 0.93, 95%CI 0.89-0.97) and odds of
      necrotizing enterocolitis (AOR 0.89, 95%CI 0.82-0.96) decreased significantly.
      Among the subgroup of 260-286 weeks' GA, the odds of composite outcome (AOR 0.63,
      95%CI 0.51-0.79), necrotizing enterocolitis (AOR 0.44, 95%CI 0.26-0.73) and
      nosocomial infection (AOR 0.64, 95%CI 0.49-0.84) were reduced. The collaborative,
      multidisciplinary, nationwide EPIQ-3 program improved outcomes of preterm
      neonates, and the improvement was sustainable over 5 years.

PMID- 30273499
TI  - The effectiveness of voluntary policies and commitments in restricting unhealthy
      food marketing to Canadian children on food company websites.
AB  - Marketing unhealthy foods and beverages to children (M2K) fosters poor dietary
      patterns, increasing obesity and noncommunicable disease risk. Federal
      restrictions on M2K have been under development in Canada since 2016; however, at
      present, M2K is mostly self-regulated by food companies. This study aimed to
      compare M2K on Canadian websites of food companies with and without voluntary
      policies or commitments in this area. A systematic content analysis of company
      websites was conducted in spring/summer 2017 for major packaged food (n = 16),
      beverage (n = 12), and restaurant chain (n = 13) companies in Canada. M2K
      policies were sourced from company websites and published corporate documents.
      Sixteen companies (43%) reported national and/or global M2K policies, while 21
      companies (57%) had no published policies. The websites of Canadian companies (n
      = 154) were scanned for child-directed products and marketing; type and frequency
      of marketing techniques were recorded. Child-directed marketing appeared on 19
      websites of 12 companies (32%), including 9 companies with M2K policies. Websites
      featured products with unconventional flavours, colours, shapes, or child
      oriented packaging, and used promotional characters, contests, games, activities,
      or lettering and graphics appealing to children. The nutritional quality of
      products marketed to children was evaluated using a nutrient profile model
      developed by Health Canada for proposed M2K regulations. Of the 217 products
      marketed to children, 97% exceeded Health Canada's proposed ~5% Daily Value
      threshold for saturated fat, sodium, and/or sugars, 73% of which were products
      from 9 companies with policies. These findings highlight the limitations of self
      regulation in restricting M2K on food company websites, reinforcing the need for
      government regulations.

PMID- 30273500
TI  - Concurrent exercise circuit protocol performed in public fitness facilities meets
      the ACSM guidelines for energy cost and metabolic intensity among older adults in
      Rio de Janeiro City.
AB  - The present study investigated whether a single bout of concurrent exercise (Ex
      Rx) at Third Age Academies (TAAs) of Rio de Janeiro City meets the American
      College of Sports Medicine (ACSM) guidelines for energy cost and metabolic
      intensity in older adults. Nine subjects (5 males and 4 females, aged 63-80
      years) visited the laboratory for clinical screening, anthropometrical, resting
      and maximal VO2 assessments. Thereafter, subjects performed an Ex Rx circuit,
      consisting of a single circuit alternating aerobic and resistance exercises at
      outdoor exercise equipment using body mass as the load (total of 9 exercises, 1-2
      sets of 15 repetition). Expired gases were collected during exercise bouts via a
      metabolic cart. The mean observed energy cost value of 169.1 kcal was slightly
      greater than the minimum value of 150 kcal reported in the ACSM's guidelines (p =
      0.018). Like energy cost, all the intensity markers adopted to analyze the
      physiological strain induced by the Ex Rx circuit significantly exceeded their
      reference values for moderate-intensity [reference values: 3.2 METs (mean
      observed value = 4.6 METs, p = 0.002); 40% of oxygen uptake reserve (mean
      observed value = 51.5%, p = 0.040); 40% of heart rate reserve (mean observed
      value = 64.1%, p < 0.001), according to the ACSM's guidelines. In conclusion, a
      single bout of Ex Rx circuit performed in TAAs at Rio de Janeiro City was able to
      induce a physiological strain (i.e. energy cost and intensity) compatible with
      the ACSM recommendations for eliciting health benefits among older adults.

PMID- 30273501
TI  - Evaluation of MOS social support in low-income caregivers of African American
      children with poorly controlled asthma.
AB  - OBJECTIVE: The purpose of this study was to examine the factor structure of the
      Medical Outcomes Study Social Support Survey (MOS-SSS) in a sample of low-income,
      urban caregivers of African American children with poorly controlled asthma.
      Although the MOS-SSS is a commonly used measure of social support, its
      psychometric properties have not been studied in this population. METHODS:
      Confirmatory factor analysis was conducted to determine the most appropriate
      factor structure for the MOS-SSS in caregivers of African American children with
      frequent Emergency Department visits for uncontrolled asthma. The following
      models were tested and compared using established fit statistics: an 18-item
      second-order four factor model, an 18-item four factor model, a bifactor model
      and an 18-item one factor model with nested models. RESULTS: Participating
      caregivers were single (75.6%) and female (97%). An 18-item one factor version of
      the scale had the best fit statistics compared to the other models tested:
      [Formula: see text](142) = 308.319, p > 0.001; Root mean square error of
      approximation (RMSEA) = 0.077; CFI (Comparative Fit Index) = 0.990; and Tucker
      Lewis Index (TLI) = 0.988. Construct validity was supported by a statistically
      significant negative relationship between our final MOS-SSS model and caregiver
      depressive symptoms ([Formula: see text]= -0.374, p < 0.001). CONCLUSIONS: The 18
      item one factor MOS-SSS may be appropriate for use in research and clinical
      practice with caregivers of African American children with poorly controlled
      asthma. It appears promising as a mechanism to advance understanding of
      relationships between social support and asthma outcomes in this vulnerable
      population.

PMID- 30273502
TI  - The association of prenatal risk factors with childhood asthma.
AB  - OBJECTIVE: The purpose of the study was to examine the relationship of maternal
      complications during pregnancy and prenatal exposures with childhood asthma among
      low-income families in Karachi, Pakistan. METHODS: Parents/guardians of children
      with and without asthma visiting a charity hospital were enrolled. Information
      about prenatal and perinatal exposures was collected. Univariable and multiple
      stepwise logistic regression analysis were conducted to explore the relationship
      of socio-demographic, maternal complications during pregnancy, access to prenatal
      care, and exposure to animals and pests while pregnant with childhood asthma.
      RESULTS: Maternal symptoms of nocturnal cough (adjusted OR [aOR = 2.87, 95% CI =
      1.60-5.14) and wheezing (aOR = 5.57, 95% CI = 2.32-13.37) during pregnancy
      significantly increased the odds of childhood asthma. The family history of
      asthma or hay fever, also elevated the odds of childhood asthma (adjusted OR
      [aOR] = 5.86 (3.03-11.34). The odds of asthma among children whose mothers
      received prenatal care by Dai, an unskilled health worker, were significantly
      elevated. Lastly, prenatal exposure to rats/mice and contact with goats while
      pregnant was significantly associated with childhood asthma. Whereas, prenatal
      exposure to cows/cattle reduces the odds of childhood asthma. CONCLUSIONS: This
      study identified important maternal and prenatal risk factors for childhood
      asthma, the majority of which are avoidable. Appropriate steps are needed to
      create awareness about the prenatal risk factors in this population.

PMID- 30273503
TI  - Osmolytes in vaccine production, flocculation and storage: a critical review.
AB  - Small molecule osmolytes, responsible for protecting stresses have long been
      known to rescue proteins and enzymes from loss of function. In addition to
      protecting macromolecules integrity, many osmolytes also act as potential
      antioxidant and also help to prevent protein aggregation, amyloid formation or
      misfolding, and therefore are considered promising molecules for
      neurodegenerative and many other genetic diseases. Osmolytes are also known to be
      involved in the regulation of several key immunological processes. In the present
      review we discuss in detail the effect of these compounds on important aspects of
      vaccines i.e., increasing the efficiency, production and purification steps. The
      present review therefore will help researchers to make a better strategy in
      vaccine production to formulation by incorporating specific and appropriate
      osmolytes in the processes.

PMID- 30273504
TI  - Patients' Needs of Religion/Spirituality Integration in Two Mental Health Clinics
      in the Netherlands.
AB  - INTRODUCTION: In the last decades, the attention for religion/spirituality (R/S)
      in mental health care (MHC) has considerably increased. However, patients'
      preferences concerning R/S in treatment have not often been investigated. The aim
      of this study was to find out how patients in clinical multidisciplinary MHC want
      R/S to be addressed in their care. METHODS: Thirty-five semi-structured
      interviews were carried out between September 2015 and July 2016 among patients
      in a secular and a Christian MHC in the Netherlands. Qualitative inductive
      content analysis was performed, using Atlas Ti. RESULTS: Patients appreciated (1)
      individual R/S conversations between patients and care team members (mainly
      nurses), (2) a familiar R/S environment, (3) a special R/S program and (4)
      contact with their R/S network. Patients varied in their presentation of R/S care
      needs from (a) explicit, mostly in the Christian MHC, to (b) implicit,
      predominantly in the secular MHC, or showed (c) hidden R/S care needs. A non
      acute stage of the illness and R/S affinity of the mental health professionals,
      were classified as possible conditions for addressing R/S. Discussion and
      implications for practice: Nurses are recommended to be aware of the diversity of
      patients' R/S care needs. Actively addressing R/S may help in recognizing
      implicit or even hidden R/S care needs. Further considerations on whether and how
      to respond to patients' R/S care needs would be justified.

PMID- 30273505
TI  - CMTR1-ALK: an ALK fusion in a patient with no response to ALK inhibitor
      crizotinib.
AB  - The targeted treatment of advanced non-small cell lung cancer (NSCLC) harboring
      genomic rearrangement of ALK is a paradigm for personalized oncology. More than
      15 different ALK fusion partners have been discovered in NSCLC patients. Most of
      these ALK fusions responded well to the ALK inhibitor crizotinib. Crizotinib is
      an oral MET/ALK inhibitor used as first-line therapy in the treatment of advanced
      NSCLC harboring ALK rearrangement. An understanding of the mechanisms by which
      tumors harbor primary drug resistance or acquired resistance to targeted
      therapies is critical for predicting which patients will respond to a specific
      therapy and for the identification of additional targetable pathways to maximize
      clinical benefits. Cap methyltransferase 1(CMTR1) also known as hMTr1, which is
      translate a human cap1 2'-o-ribose methyltransferase. Here, we report the newly
      found ALK fusion, CMTR1-ALK, in a patient who has no response to the ALK
      inhibitor crizotinib. The results remind us that detecting ALK status is
      important, but that determining the ALK fusion type and function may be more
      important for patient.

PMID- 30273506
TI  - Meningococcal disease in adolescents and young adults: a review of the rationale
      for prevention through vaccination.
AB  - Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is
      characterized by high mortality and morbidity. While IMD incidence peaks in both
      infants and adolescents/young adults, carriage rates are often highest in the
      latter age groups, increasing IMD risk and the likelihood of transmission.
      Effective vaccines are available for 5 of 6 disease-causing serogroups. Because
      adolescents/young adults represent a significant proportion of cases, often have
      the highest carriage rate, and have characteristically low vaccination adherence,
      efforts should be focused on educating this population regarding long-term
      consequences of infection and the importance of meningococcal vaccination in
      prevention. This review describes the role of adolescents/young adults in
      meningococcal transmission and the clinical consequences and characteristics of
      IMD in this population. With a focus on countries with advanced economies that
      have specific meningococcal vaccination recommendations, the epidemiology of
      meningococcal disease and vaccination recommendations in adolescents/young adults
      will also be discussed.

PMID- 30273507
TI  - Comparison of three sample size calculation methods for non-inferiority vaccine
      trials with multiple continuous co-primary endpoints.
AB  - Clinical trials that study immunogenicity of combination vaccines often have less
      power than desirable. To make up for the reduction in statistical power at the
      study level, researchers have to increase the study sample size. To study
      immunogenicity variables, we used the geometric mean concentration of immune
      response after vaccination as immunologic endpoint and compared 3 sample size
      calculation methods: the "Inflation factors" method, the "Incrementing" method,
      and the "Bonferroni correction" method when there are multiple continuous co
      primary endpoints. The parameters were set according to the actual situation of
      the use of combination vaccines and the simulation results were used as
      reference. The present study demonstrates that all 3 methods are applicable when
      the effect size of each endpoint is similar and the endpoints are at most weakly
      correlated, but when there is a true difference in effect sizes among endpoints,
      the "Incrementing" method has the best performance.

PMID- 30273508
TI  - Recruitment, use, and satisfaction with a web platform supporting families of
      children with suspected or diagnosed developmental coordination disorder: a
      randomized feasibility trial.
AB  - OBJECTIVES: To determine the feasibility of recruiting families of children with
      suspected or diagnosed developmental coordination disorder (sdDCD) and explore
      their satisfaction with a web-based intervention Design. A feasibility randomized
      trial was conducted. Participants were the parents of 5-12-year-old children with
      sdDCD. The intervention group had access to online resources, group and private
      forums, and videoconferencing with a therapist. Main outcomes were recruitement
      and retention rates. Satisfaction was documented through a post-intervention
      survey and interview. RESULTS: The recruitment rate was seven participants per
      month (n = 28 participants) and retention rate was 68%. Satisfaction was
      moderate. No differences in use and satisfaction were observed between groups.
      Participants formulated recommendations for improving the intervention, including
      targeting families earlier in the diagnosis process, and pre-scheduling meetings
      with therapists. CONCLUSIONS: This study demonstrated the feasibility of future
      trials, and highlighted avenues for improvement. Parent involvement during the
      development of the intervention is discussed at length. ABBREVIATIONS: DCD:
      Developmental Coordination Disorder; sdDCD: suspected or diagnosed Developmental
      Coordination Disorder; RCT: randomized-controled trial.

PMID- 30273509
TI  - Variation factors of stereotypical hand movements in subjects with Rett syndrome.
AB  - BACKGROUND: Stereotypical hand movements have been observed in most individuals
      diagnosed with Rett syndrome. OBJECTIVES: To investigate factors that increase or
      decrease hand stereotypies in individuals with Rett syndrome. METHODS: A
      questionnaire regarding hand stereotypies or purposeful hand behaviours was sent
      to 1016 schools for special needs education and 204 facilities in Japan. RESULTS:
      Information was acquired from 216 cases (3-53 years old) with Rett syndrome;
      81.9% and 87.6% of individuals had factors that increased and decreased
      stereotypical hand movements, respectively. Stereotypies were mainly increased by
      displeasure (63.8%) or pleasure (48.5%), and decreased by somnolence (43.5%),
      pleasure (30.0%), or food (24.1%). CONCLUSION: Emotion was the main factor
      increasing stereotypical hand movements, whereas there were a large number of
      factors that decreased these movements. The factors that decrease stereotypies
      could be useful to prevent the skin problems or joint contracture observed in
      patients with Rett syndrome.

PMID- 30273510
TI  - Dupilumab safety and efficacy in uncontrolled asthma: a systematic review and
      meta-analysis of randomized clinical trials.
AB  - OBJECTIVE: We aimed to perform a meta-analysis evaluating the efficacy and safety
      of dupilumab in patients with uncontrolled asthma. DATA SOURCE: A search of
      electronic databases was performed using PubMed, Cochrane library and Embase.
      STUDY SELECTION: The literature search was conducted independently by two
      reviewers. Only randomized controlled trials (RCTs) that compared between placebo
      and dupilumab in patients with uncontrolled asthma were included in this
      analysis. Pooled risk ratios (RRs) and mean differences (MDs) with their
      corresponding 95% confidence intervals (CIs) were calculated for dichotomous and
      continuous data, respectively. RESULTS: A total of four RCTs representing 2,992
      patients were included. Pooled analysis showed significant reductions of the
      annualized rate of severe asthma exacerbation in the dupilumab group compared
      with placebo (RR 0.44; 95% CI 0.35-0.055; P < 0.01; I2 = 42%). In addition, the
      absolute forced expiratory volume at 1 s (FEV1) changes were significantly
      increased for the dupilumab group (MD 0.14; 95% CI: 0.12-0.17; P < 0.01; I2 =
      0%). Finally, there were no significant differences between both groups in the
      development of any adverse event, serious adverse events, adverse events leading
      to death, discontinuation of medication due to adverse event or the occurrence of
      upper respiratory tract, influenza or bronchitis infections. However, dupilumab
      was associated with an increased risk of injection site reactions compared with
      placebo (RR 1.91; 95% CI 1.41, 2.59; P < 0.01; I2 = 24%). CONCLUSION: Among
      patients with uncontrolled asthma, the addition of dupilumab was associated with
      a reduced risk of severe asthma exacerbations and improvement in FEV1 without an
      increased risk of adverse events apart from injection site reactions with
      dupilumab.

PMID- 30273511
TI  - On the lighter side: Medicine or etiquette? Rethinking a lecturer's teaching
      assignment.
AB  - PURPOSE: To investigate the extent to which medical students demonstrate
      politeness. With respect to patient-physician interactions, politeness appears to
      be a factor in therapeutic success, perhaps because it might induce greater
      patient compliance. METHOD: We assessed 354 third-semester medical students on
      one type of politeness, that is the percentage of students who greeted the
      teacher upon entering the lecture room. RESULTS: Overall, 47% of the students
      initiated a greeting and this percentage did not change when the lecturers wore
      white coats. Females were less likely to initiate a greeting (35%) than males
      (55%). CONCLUSION: The results lead us to question whether university lecturers
      should strictly stick to their content of the curriculum or should they also
      teach their students about etiquette related to good clinician-patient
      relationships?

PMID- 30273513
TI  - Disease of the Year: Differential Diagnosis of Uveitic Macular Edema.
AB  - Uveitic cystoid macular edema (UME) is an important cause of visual morbidity
      among patients with both infectious and non-infectious uveitis. UME may be
      associated in more than 30% cases of active uveitis. However, even patients with
      minimal features of intraocular inflammation may develop recurrent or chronic
      UME. Therefore, the evaluation and management of UME in patients with uveitis may
      be challenging. A number of vitreoretinal pathologies may result in UME and
      accumulation of fluid in the intra- or subretinal space. These need to be
      carefully distinguished from each other so that appropriate management can be
      initiated. All types of uveitis, including anterior uveitis (where the primary
      site of inflammation is not in the posterior segment) can present with UME. Other
      conditions such as diabetes, and surgery, can present with macular edema. This
      index review highlights various differential diagnoses of UME and provides
      illustrative case examples with multimodal imaging evaluation.

PMID- 30273512
TI  - A simple and safe antibody neutralization assay based on polio pseudoviruses.
AB  - The evaluation of the immunogenicity of Sabin strain based Inactivated Poliovirus
      Vaccines (sIPV) necessitates the use of wild strains in neutralization assays to
      assess the potential cross-reactivity of antibodies. The live virus strains
      including wild and Sabin strains must be handled in level 3 biocontainment
      laboratories. To develop an alternative assay without the use of a live virus, we
      constructed Mahoney, MEF-1, and Saukett pseudovirions by inserting luciferase
      reporter genes into intact capsid proteins. Afterward, we developed a pseudovirus
      based neutralization test (pNT) and evaluated for the specificity and
      reproducibility. We tested serum samples from a clinical trial on sIPV vaccines
      by pNT and compared the results with those obtained from conventional
      neutralization tests (cNT). A strong correlation was observed between two
      methods, with the correlation coefficients of all three types of IPV vaccines
      being greater than 0.82 (p < 0.0001). The Geometric Mean Titer (GMT) values
      obtained by pNT were approximately four times higher than that by cNT, revealing
      the better sensitivity of pNT. In conclusion, pNT is a safe, rapid and sensitive
      quantitative assay with the potential of being an alternative for the evaluation
      of the potency of polio vaccines.

PMID- 30273514
TI  - Effect of Rapamycin Microspheres in Sjogren Syndrome Dry Eye: Preparation and
      Outcomes.
AB  - PURPOSE: To prepare a drug delivery system of rapamycin poly-3-hydroxybutyrate-co
      3-hydroxyvalerate microspheres (RPM) and analyze its effect on the eyes of a
      Sjogren's syndrome mouse model. METHODS: RPM was generated using a solvent
      evaporation method, and observed under light and electron microscopy. No obesity
      diabetes (NOD) mice with Sjogren's syndrome were randomized into normal saline,
      empty microspheres, and RPM groups, with healthy Kunming mice as the controls.
      Dry eye signs were assessed using a slit lamp. Tear secretion, corneal
      fluorescein, keratoconjunctival rose bengal, and conjunctival impression cytology
      were recorded. RESULTS: RPM was smooth and spherical, about 20-50 MUm in
      diameter, without agglomeration or adhesion. Mice receiving RPM secreted more
      tears. And they had a normal corneal histology, exhibiting reduced corneal
      fluorescein, rose bengal staining, and conjunctival impression cytology.
      CONCLUSION: RPM improved the signs of dry eyes, improved tear secretion,
      decreased corneal endothelial cell injury, and improved histological damage of
      the cornea in NOD mice.

PMID- 30273515
TI  - The Use of Differential Reinforcement of Other Behaviours to Establish Inhibitory
      Stimulus Control for the Management of Vocal Stereotypy in Children with Autism.
AB  - OBJECTIVE: This study examined the efficacy of an inhibitory stimulus control
      procedure (ISCP) for the management of vocal stereotypy in three children with
      autism. METHOD: During discrimination training, implemented within a changing
      criterion design, participants were taught that there were no consequences for
      vocal stereotypy in the absence of an inhibitory stimulus but that differential
      reinforcement procedures were in effect in the presence of the stimulus.
      Functional control of the inhibitory stimulus was subsequently assessed within a
      reversal design. RESULTS: Inhibitory stimulus control was established during
      discrimination training, with participants inhibiting vocal stereotypy for 30 min
      periods in the presence of the inhibitory stimulus. Reductions in vocal
      stereotypy were maintained in the presence of the inhibitory stimulus and in the
      absence of further programmed consequences. DISCUSSION: This study extends
      current knowledge by demonstrating the efficacy of ISCPs paired with
      reinforcement only, and illustrating the functional control of the inhibitory
      stimulus.

PMID- 30273516
TI  - Glutaminase inhibitors: a patent review.
AB  - INTRODUCTION: The kidney-type glutaminase (GLS) controlling the first step of
      glutamine metabolism is overexpressed in many cancer cells. Targeting inhibition
      of GLS shows obvious inhibitory effects on cancer cell proliferation. Therefore,
      extensive research and development of GLS inhibitors have been carried out in
      industrial and academic institutions over the past decade to address this unmet
      medical need. Areas covered: This review covers researches and patent literatures
      in the field of discovery and development of small molecule inhibitors of GLS for
      cancer therapy over the past 16 years. Expert opinion: The detailed ligand
      receptor interaction information from their complex structure not only guides the
      rational drug design, but also facilitates in silico structure-based virtual
      ligand screening of novel GLS inhibitors. Multi-drug combination administration
      is of great significance both in terms of safety and efficacy.

PMID- 30273517
TI  - Long-term physical and mental health outcomes associated with traumatic brain
      injury severity in post-9/11 veterans: A retrospective cohort study.
AB  - OBJECTIVES: To examine long-term outcomes of self-reported physical and mental
      health among Post-9/11 Veterans stratified by traumatic brain injury (TBI)
      severity, we hypothesized that more severe TBI would be associated with
      significantly poorer outcomes. METHODS: A prospective longitudinal survey of
      physical and mental health status was conducted with a national cohort of Post
      9/11 Veterans. We then used generalized linear models (GLM) to assess the unique
      contribution of TBI severity on long-term outcomes after controlling for socio
      demographic characteristics, comorbidity phenotypes, and deployment experiences.
      RESULTS: TBI of any severity was associated with significantly poorer outcomes
      relative to the No TBI group. However, the manifestation of these outcomes
      identified in our study differed meaningfully by TBI severity level. CONCLUSIONS:
      Veterans with any TBI exposure experience poorer long-term outcomes than those
      with no TBI even when covariates are considered. In particular, measures of
      somatization, PTSD symptom distress, and depression indicate pervasive and long
      term health concerns among individuals with TBI. Additional research is required
      to fully explicate what appear to be complex relationships among TBI severity,
      physical and mental well-being, combat exposures, and socioeconomic resources in
      this population.

PMID- 30273518
TI  - Mitogen-activated protein kinase kinase 6 negatively regulates anthocyanin
      induction in Arabidopsis.
AB  - Arabidopsis mitogen-activated protein (MAP) kinase kinase 6 (MKK6) has previously
      been shown to play important roles in plant immunity and cytokinesis. Here we
      report that it is also involved in the negative regulation of anthocyanin
      biosynthesis in Arabidopsis. Elevated anthocyanin levels are observed in mkk6
      knock out mutant plants. RNA-sequencing analysis revealed that the expression
      level of MYB75 (Myb transcription factor 75), which encodes a key positive
      regulator of anthocyanin biosynthesis, is up-regulated in mkk6 mutant plants,
      suggesting that increased MYB75 expression contributes to the elevated
      anthocyanin levels. In addition, suppression of high sucrose-induced anthocyanin
      production by pathogen associated molecular pattern-triggered immunity is also
      dependent on MKK6, further supporting that MKK6 is a key negative regulator of
      anthocyanin biosynthesis in Arabidopsis.

PMID- 30273519
TI  - Quality of dying and quality of end-of-life care of nursing home residents in six
      countries: An epidemiological study.
AB  - BACKGROUND:: Nursing homes are among the most common places of death in many
      countries. AIM:: To determine the quality of dying and end-of-life care of
      nursing home residents in six European countries. DESIGN:: Epidemiological survey
      in a proportionally stratified random sample of nursing homes. We identified all
      deaths of residents of the preceding 3-month period. Main outcomes: quality of
      dying in the last week of life (measured using End-of-Life in Dementia Scales -
      Comfort Assessment while Dying (EOLD-CAD)); quality of end-of-life care in the
      last month of life (measured using Quality of Dying in Long-Term Care (QoD-LTC)
      scale). Higher scores indicate better quality. SETTING/PARTICIPANTS:: Three
      hundred and twenty-two nursing homes in Belgium, Finland, Italy, the Netherlands,
      Poland and England. Participants were staff (nurses or care assistants) most
      involved in each resident's care. RESULTS:: Staff returned questionnaires
      regarding 1384 (81.6%) of 1696 deceased residents. The End-of-Life in Dementia
      Scales - Comfort Assessment while Dying mean score (95% confidence interval)
      (theoretical 14-42) ranged from 29.9 (27.6; 32.2) in Italy to 33.9 (31.5; 36.3)
      in England. The Quality of Dying in Long-Term Care mean score (95% confidence
      interval) (theoretical 11-55) ranged from 35.0 (31.8; 38.3) in Italy to 44.1
      (40.7; 47.4) in England. A higher End-of-Life in Dementia Scales - Comfort
      Assessment while Dying score was associated with country ( p = 0.027), older age
      ( p = 0.012), length of stay ?1 year ( p = 0.034), higher functional status ( p <
      0.001). A higher Quality of Dying in Long-Term Care score was associated with
      country ( p < 0.001), older age ( p < 0.001), length of stay ?1 year ( p <
      0.001), higher functional status ( p = 0.002), absence of dementia ( p = 0.001),
      death in nursing home ( p = 0.033). CONCLUSION:: The quality of dying and quality
      of end-of-life care in nursing homes in the countries studied are not optimal.
      This includes countries with high levels of palliative care development in
      nursing homes such as Belgium, the Netherlands and England.

PMID- 30273520
TI  - Hispanic Caregiver Experiences Supporting Positive Postschool Outcomes for Young
      Adults With Disabilities.
AB  - The rate of competitive employment, or employment in community settings for
      minimum wage or higher, of working-age individuals with disabilities trails
      behind individuals without disabilities in the United States. These statistics
      are even more alarming among Hispanic individuals who have disabilities. The
      purpose of this study was to explore the negative and positive experiences of
      Hispanic caregivers from a Midwestern state as they support their family members
      with disabilities to achieve positive postschool outcomes, including competitive
      employment. We conducted semistructured interviews with 13 caregivers of family
      members with disabilities aged 14-25 years. Three key themes emerged from our
      analysis: (a) negative experiences with school educators, (b) negative
      experiences with community-based service providers, and (c) positive experiences
      and strategies for overcoming barriers. Implications for practice and future
      research are discussed.

PMID- 30273521
TI  - Introduction to the Special Issue on Partnering With Families of Individuals With
      Developmental and Intellectual Disabilities Throughout the Lifespan.

PMID- 30273522
TI  - "We Had to Keep Pushing": Caregivers' Perspectives on Autism Screening and
      Referral Practices of Black Children in Primary Care.
AB  - Black children with autism spectrum disorder (ASD) are diagnosed later than their
      White peers, are more likely to be misdiagnosed, and are less likely to receive
      early intervention services or a developmental evaluation by three years old.
      Using a grounded theory approach, we solicited the perspectives of parents and
      other primary caregivers of Black children with ASD on barriers and facilitators
      to ASD screening and referrals in primary care. A socioeconomically diverse
      sample of 22 female caregivers participated. Four themes emerged. First, while
      some caregivers noted their child's primary healthcare providers facilitated a
      timely ASD diagnosis, other participants reported these providers ignored early
      concerns about child developmental delays. Second, many participants felt racial
      bias negatively impacted caregiver-primary healthcare provider interactions.
      Third, legal/custodial issues slowed caregivers' abilities to follow up on
      referrals from their primary healthcare providers. Finally, caregivers described
      denial, shame, and stigma relating to ASD in the Black community as possible
      factors for delayed follow up to referrals. Differences based on socioeconomic
      status are discussed. Efforts to improve family-centered, culturally relevant
      care for all Black caregivers raising children with or at-risk for ASD are
      needed, particularly for those families experiencing the multiple effects of
      poverty.

PMID- 30273524
TI  - Resumes en Francais.

PMID- 30273523
TI  - Grandparents of Children With Intellectual and Developmental Disabilities:
      Navigating Roles and Relationships.
AB  - Grandparents can play critical roles in the lives of children with intellectual
      and developmental disabilities and their families. However, current research and
      understanding around grandparent roles and experiences is limited. The purpose of
      this qualitative study was to examine the roles and experiences of grandparents
      supporting children with disabilities. In this article, the voices of
      grandparents with diverse experiences are presented. Key themes that emerged were
      the role of the grandparent, boundaries in roles and space, navigating family
      dynamics, and the general experiences of grandparenting. These findings have
      implications for the types of supports provided to grandparents and for
      practitioners working with families who have actively involved grandparents.

PMID- 30273525
TI  - Empowerment and Resilience in Families of Adults With Intellectual and
      Developmental Disabilities.
AB  - Using the family resilience model, we examined the association between
      empowerment, family member age, length of institutionalization, and resilience
      among family members of relatives with intellectual and developmental
      disabilities (IDD) following deinstitutionalization. Participants included 56
      family members whose relatives with IDD recently transitioned to community
      living. Results strongly indicate empowerment plays a key role in positive family
      adaptation. Thus, following a relative's move from an institution to the
      community, empowerment is a promising form of protection that holds potential to
      increase family resilience. The results of the current study support the family
      resilience model as a foundation for future research regarding how families
      navigate significant transitions throughout the lifespan. Implications for
      practice and policy are provided.

PMID- 30273527
TI  - Resumenes al Espanol.

PMID- 30273526
TI  - Parent Engagement in the Transition From School to Adult Life Through Culturally
      Sustaining Practices: A Scoping Review.
AB  - The increasingly diverse population in the United States calls for schools to
      address the breadth of cultural histories students bring with them to the
      classroom. High school students with disabilities are also diverse in terms of
      cultural histories, race, ethnicities, religions, and citizenship. These factors
      intersect as families engage in planning for the transition to adulthood. A
      requisite for culturally diverse families with young adults who receive services
      under the educational category of intellectual disability (ID) are school
      professionals who can meaningfully collaborate. This review of literature from
      peer-reviewed journals seeks to understand if culturally responsive practices are
      utilized with culturally and linguistically diverse (CLD) families during
      transition planning. This review also explored whether culturally sustaining
      practices strengthen partnerships between teachers and CLD families and
      adolescents with disabilities, including those with ID. Implications are
      associated with how teachers can perceive diversity from a strengths perspective
      as a vital component of transition planning.

PMID- 30273528
TI  - [Measles Outbreak]

PMID- 30273529
TI  - [Magnetic resonance as initial screening diagnosis of secondary involvement of
      central nervous system in NHL diffuse large B cell lymphoma]
AB  - Background: Background: Central Nervous System (CNS) relapse in Diffuse Large B
      cell Lymphoma occurs mostly 6-8 months after disease onset. This has led to
      propose that CNS infiltration is an early event in the evolution of the disease.
      We intend to evaluate the role of magnetic resonance imaging (MR) at diagnosis to
      detect early SNC compromise. Methods: Prospective longitudinal cohort's study in
      DGCB patients treated at Hospital de Clinicas between 2013 and 2015. Skull MRI
      was performed in all patients at diagnosis and lumbar puncture was done according
      to predefined risk factors. Results: 35 patients were analyzed. Median age: 68
      years (24-85 years). Stage III-IV: 62%, 57% good prognosis according to RIPI
      score and 43% poor prognosis. MRI was performed in all patients, with no
      pathological findings in any of them. Twenty-one patients fullfilled criteria for
      cerebrospinal fluid study. Twenty-two patients were studied and received
      intrathecal methotrexate prophylaxis. Meningeal relapse was observed in a single
      patient who had negative studies at diagnosis and had received complete
      prophylaxis at the end of the 6 R-CHOP series. Conclusions: Only one of the 35
      patients relapsed in the CNS. This patient had a noral MRI and CSF study at
      diagnosis and had received prophylaxis with intrathecal chemotherapy. This
      results lead us to believe that the value of MRI to detect early infiltration in
      asymptomatic patients at diagnosis is low.

PMID- 30273530
TI  - [Laparoscopic Surgery for isolated lymph nodes recurrence in gynecology.
      Experience in Argentina.]
AB  - Objectives: to describe the perioperative and oncological outcomes of a serie of
      cases treated with laparoscopic surgery for isolated nodal metastasis of
      gynecologic malignancies at the Gynecology Service of Hospital Italiano de Buenos
      Aires and conduct a literature review on the surgical treatment provided to
      patients with this condition. Methods: A search was conducted in the surgery
      records of the Gynecology Service of Hospital Italiano of patients who underwent
      laparoscopic cytoreductive surgery for isolated nodal recurrence of a gynecologic
      primary tumor in the period 2009-2015. The medical records were reviewed and data
      on the patients' characteristics, the tumor, the surgery and its complications
      were collected and analyzed. A literature search was conducted in Pubmed by the
      term "isolated nodal recurrence in gynecology" and a subsequent snowball search
      was performed. Results: As results, nine patients are presented. The median age
      was 66 years old (RI 7). The initial cancer location was: ovary (n=3),
      endometrium (n=3), cervix (n=2) and breast (n=1). The location site of the single
      nodal recurrence was the para-aortic area (n=8) and the pelvic area (n=1). The
      median of the disease-free interval to recurrence was 42.8 months (RI 40.2).
      Either the retroperitoneal or the transperitoneal approach was used based on the
      location of the recurrence. The median surgery time was 120 minutes (RI 36). No
      conversion to laparotomy was performed in any patient. No intraoperative or
      postoperative complications were reported, nor any requirement for blood
      transfusion. The median hospital stay was 36 hours. Adjuvant treatment with
      chemotherapy was applied to 8/9 patients. Only one patient recurred in para
      aortic lymph nodes and peritoneal carcinomatosis after eight months and died of
      her disease. The literature review confirms the possibility of laparoscopic
      resection of the single nodal recurrence with low complication rate. Conclusion:
      The laparoscopic lymph node cytoreductive surgery is a valid and safe treatment
      option considering the perioperative and oncological outcomes in our hospital.

PMID- 30273531
TI  - Incidence of hospital-acquired venous thromboembolic disease.
AB  - BACKGROUND: There is limited knowledge of the incidence of venous thromboembolic
      disease (VTE) during hospitalization, since most of these are community-based
      data. PURPOSE: To estimate the incidence rate (IR) of VTE developed during
      hospitalization. METHODS: Prospective cohort of all inpatients admitted in a
      university tertiary hospital, in Argentina. The inclusion criteria were defined
      as: adult patients consecutively admitted from July/2006 to August/2013, for any
      cause. Patients admitted for VTE were excluded; all patients at the time of
      admission were free of event. Each person was followed contributing time at risk,
      from admission to event, discharge or death. VTE incident cases were captured
      from the Institutional Registry of Thromboembolic Disease (ClinicalTrials.gov
      Identifier NCT01372514). Incidence rate was calculated with 95% confidence
      intervals. RESULTS: The crude incidence rate of VTE for clinical patients was
      0.49 (95%CI 0.45-0.55) per 1,000 cases person-days, and IR adjusted for WHO was
      0.23 (95%CI 0.19-0.26). The crude IR of VTE for surgical patients was 0.25 (95%CI
      0.23-0.27), and IR adjusted for WHO was 0.13 (95%CI 0.10-0.17). The incidence
      rate ratio (IRR) for VTE shows that surgical admission reduces the IRR and age
      categories increases the thrombosis rate risk, after adjustment for age category,
      sex and surgical admission. CONCLUSIONS: This study suggests that there is a high
      risk of VTE in hospitalized patients and is still a frequent problem.

PMID- 30273532
TI  - [School Agroecology and health-related quality of life to adolescents]
AB  - The study aimed to evaluate the contribution of school agroecology to the quality
      of life related to health of adolescents of a school of Cordoba, Argentina.
      Feasibility study. It was a study quasi- experimental whit control group carried
      out in a middle-level public school. The sample consisted of 58 adolescents in
      the intervention group and 77 in the control group. After the intervention
      increased consumption of agro-ecological food (from 26% to 74% p<0,05). Changes
      were detected in acquired knowledge about agroecology in the classroom level
      going from 37% to 63% (p< 0,05). Positive changes detected in awareness with the
      environment and relationship (p<0,05). It was evidenced that the implementation
      of school agroecology can provide resolutive contributions to some of the
      problems the health related quality of life of adolescents.

PMID- 30273533
TI  - [The nutritional status analysis in physical education students, associated with
      eating habits and level of physical activity]
AB  - INTRODUCTION: numerous studies show that the college-aged student modifies their
      eating habits and levels of physical activity and, consequently, their Body Mass
      Index (BMI) exceeds healthy values (?25). General objective: to analyze the
      nutritional status in students of two Physical Education Teaching training
      Institutes, located in Cordoba, Argentina, and their possible association with
      eating behaviours and level of physical activity. Method: observational, cross
      sectional and descriptive study. 134 students were studied.To assess nutritional
      status, the MBI was measured. To investigate about food selection and habits
      which accompanied the ingestion, a survey was used based on the recommendations
      from the Food Guidelines for the Argentine Population. To estimate energy
      expenditure by physical activity, the International Physical Activity
      Questionnaire (IPAQ) was used, in short format, in the Spanish version. Results:
      Se podria presumir que el saludable estado nutricional de la poblacion estudiada
      se debe a sus habitos alimentarios mayormente saludables y, principalmente, a su
      alto nivel de actividad fisica. No obstante, el seguimiento de esta poblacion, en
      un estudio longitudinal, podria ratificar o rectificar estas primeras
      presunciones. Conclusion: it can be assumed that the healthy nutritional status
      of the study population is due to their mostly healthy eating habits, and mainly
      to their high level of physical activity.

PMID- 30273535
TI  - Are there any risk factors for developing complications with the use of
      retrievable vena cava filters in orthopaedic surgery?
AB  - BACKGROUND: In high-risk patients, common prophylaxis may be insufficient to
      prevent thromboembolic events after orthopaedic procedures. In this scenario, a
      retrievable vena cava filter (VCF) could be considered as an alternative,
      although it's use remains controversial. Therefore, we asked: (1) what is the
      overall mechanical complication rate associated with the use of retrievable VCFs
      in orthopaedic surgery?, (2) what is the association with thromboembolic disease
      (TED) recurrence, post-thrombotic syndrome and/or major bleeding according to
      different surgical characteristics?, (3) What is the overall mortality rate
      attributed to VCF use? METHODS: We retrospectively analyzed a cohort of 68
      patients who underwent orthopaedic surgery with a previous diagnosis of TED, in
      whom a retrievable VCF was placed. Permanent filters were excluded. We studied
      the filter's mechanical complications and considered as possible outcomes death
      and 3 hematologic complications: TED recurrence, post-thrombotic syndrome and
      major bleeding. To estimate association with risk factors, we subclassified
      surgeries into 5 groups: 1, arthroplasty/non-arthroplasty; 2, primary/revision;
      3, elective/urgent; 4, oncologic/non-oncologic; 5, preoperative/postoperative
      filter. RESULTS: Mechanical complications were 16% and required a filter
      revision. Sixty-four percent of the revised VCFs developed a mechanical failure
      and could not be retrieved. Overall prevalence of TED recurrence, post-thrombotic
      syndrome and hemorrhage was 33%, 15% and 4.5%, respectively. Spinal surgeries
      were a risk factor for developing TED recurrences.  Only 4% of patients died of a
      TED recurrence. CONCLUSIONS: Orthopaedic procedures had a high risk of mechanical
      and hematologic complications after using a retrievable VCF. However, mortality
      was low due to these complications.

PMID- 30273534
TI  - [Frequency and associated risk factors of cardiovascular autonomic neuropathy
      among patients with type 2 Diabetes.]
AB  - Background: Cardiovascular autonomic neuropathy (CAN) is a common complication of
      diabetes and is associated with cardiovascular morbidity and mortality. Despite
      its prevalence, it is usually underdiagnosed. Objective to assess frequency of
      CAN in type 2 diabetes, treated at the Diabetology Service at Cordoba Hospital,
      Argentina. Method: Cross-sectional study was conducted from May 2015 to May 2016.
      Cardiovascular Autonomic Tests (Ewing's battery) were performed: response to
      Valsalva maneuver, expiration-to-inspiration ratio (E/I ratio), standing to lying
      flat and postural hypotension. Results: 100 type 2 diabetes patients, 53%
      females. The mean age and diabetes duration 52 years old and 8.4 years,
      respectively. Hemoglobin A1c level of 8.7% and 47% were insulin-requiring type 2
      diabetes patients. 29% had early CAN, 54% confirmed CAN (10% severe CAN) and 17%
      normal cardiovascular tests. Confirmed CAN was higher in those with longer
      duration of diabetes; longer duration of insulin therapy, older patients and
      severe hypoglycemia events was higher in those with confirmed CAN versus without
      CAN or early CAN (p 0.003). The risk factors associated were hypertension OR 2.55
      (p 0.02), peripheral neuropathy OR 11.7 (p <0.0001), diabetic retinopathy OR 9.03
      (p 0.001), diabetic nephropathy OR 3.12 (p 0.03) and hemoglobin A1c > 7% OR 2.57
      (p 0, 03). Conclusions: frequency of CAN was high, was associated with
      hypertension, microvascular complications, older age, poor metabolic control,
      longer duration of disease and insulin therapy. Patients with a higher risk of
      developing CAN should be identified, in order to reduce the impact of this
      complication.

PMID- 30273536
TI  - [Filamentous fungal infection in burned patients: retrospective study.]
AB  - Introduction: Infections are the most frequent complications in burn patients.
      Filamentous fungi have an uncertain place within the statistics, since in our
      media data regarding their prevalence, causal agents and outcome of those who
      suffer them remain scarce. The aim of this study was to evaluate the prevalence
      of fungal infection by filamentous fungi (IHF) in patients hospitalized in burn
      intensive care unit (BICU), and to review clinical, epidemiological,
      microbiological and evolutionary characteristics of these patients and to know
      the frequency and distribution of the isolated fungi. Materials and methods:
      Retrospective and descriptive study. It includes all individuals admitted in
      burns intensive care unit (2012-2015), with positive culture for filamentous
      fungi in skin biopsies and bedsores. Results: A total of 168 patients were
      admitted in the BICU in a period of 3 years. 90% were major burned and 17% of
      them developed IHF (29/168).  Aspergillus spp (24%), Fusarium sp (14%), Mucor spp
      (3%) and various black fungus genera (58%) were the main genera found in
      cultives. About 24% of the patients with IHF died and Fusarium spp was found in
      50% of the cases. The cause of death was irreversible cardiogenic shock with
      multiorgan failure. Conclusions: Filamentous fungal infection was present in 17%
      of burned patients. The main isolatte fungi in samples were dematiaceous mould.
      Mortality among patients was 24%, with Fusarium being the fungus found in the
      highest number of deaths (50%).

PMID- 30273537
TI  - [Hepatic Parasitosis: Atypical presentation]
AB  - Benign solid liver tumors are composed by a heterogeneous group of lesions.
      Hepatic parasitosis is an infrequent etiological cause of benign solid liver
      tumors. Objective. To present the case of a patient with benign solid liver
      tumors treated with right portal vein embolization and, later, with hepatectomy.
      Clinical case. 60-year-old, male patient diagnosed with multiple solid liver
      tumors, due to a generalized case of jaundice. The decision to perform surgery
      was made on the basis of the clinical symptoms and the impossibility of
      discarding malignancy through complementary tests. Before surgery, hepatic
      volumetry and right portal vein embolization were done to increase future hepatic
      remnant. Right hepatectomy and hepatic resection of segment IVa were performed.
      The patient evolved positively from jaundice and the anatomopathological results
      showed a lesion related to hepatic parasitosis. Conclusion. In the presence of a
      solid liver tumor, it is necessary to rule out the malignant etiology of the
      lesion. If this is not possible, or if the patient continues with the
      symptomatology, surgical resection is prescribed, taking into account the volume
      of the hepatic gland and future hepatic remnant.

PMID- 30273538
TI  - [Nephrocalcinosis and proximal tubulopathy in Sjogren's Syndrome.]
AB  - Primary Sjogren's syndrome is a systemic and chronic autoimmune disease. Renal
      involvement may occur in up to 30% of patients. The incidence of tubulopathies
      ranges from 2.6 to 33%. They are manifested by defects in the urine concentration
      and hydroelectrolyte alterations, mainly distal tubular acidosis and
      exceptionally proximal tubular acidosis. These disorders can be associated with
      nephrocalcinosis and renal lithiasis.We report the case of a patient with primary
      Sjogren who presented proximal renal tubular acidosis associated with recurrent
      renal colic due to renal lithiasis and nephrocalcinosis.We highlight the
      importance of diagnosing renal tubular acidosis in patients with Sjogren's
      syndrome that present alterations in urinary sediment and electrolyte disorders
      to avoid nephrocalcinosis and nephrolithiasis. Acidosis correction treatment aims
      to prevent the progression of the disorder and preserve renal function.

PMID- 30273540
TI  - [Role of students of medicine in the progress of public health in Latin America.]

PMID- 30273539
TI  - [Primary ciliary disquinesia related bronchiectasis. Relevance of Pigmentary
      retinitis among clinical data.]

PMID- 30273541
TI  - [Cancer genetic counseling.]

PMID- 30273542
TI  - Premarital sexual behaviour among higher secondary students in Pokhara Sub
      Metropolitan City Nepal.
AB  - Background: Sexual behaviour of young people is one of the major public health
      issues. This is because adolescent people may involve themselves in risky sexual
      behaviour such as practising sex at an early age, having multiple sexual
      partners, having sex while under the influence of alcohol or drugs, and
      unprotected sexual behaviours. The objective of this study was to explore the
      premarital sexual behaviours among higher secondary school students in Pokhara
      Sub-Metropolitan City. Methods: This survey adopted a design of an institution
      based descriptive cross-sectional study. A pre-tested structured questionnaire
      sealed in an envelope was distributed among all consenting 522 higher secondary
      school adolescent students. Results: Nearly twenty-five per cent (24.6%) of study
      respondents have had premarital sex. Respondents who had discussed sexual matters
      with friends had a 2.62-fold higher chance of having premarital sex than those
      who had not. Male respondents were eight-fold more likely to have premarital sex
      than females. Respondents who were exposed to pornography reported a nine-fold
      higher possibility of having premarital sex. Study respondents were also involved
      in unsafe sexual practices; for example, 13.4% of male respondents had sex with
      female sex workers. Conclusion: Despite the deleterious social and cultural norms
      and values regarding premarital sexual activities school adolescents are
      increasingly involved in sexual activities before marriage. Peer groups or
      friends are major sources of sexual and reproductive health information, which is
      often insufficient and inaccurate. It is important to design an appropriate and
      effective intervention to ensure that adolescents get correct and suitable sexual
      and reproductive information.

PMID- 30273543
TI  - Salvianolic acid B attenuates experimental pulmonary inflammation by protecting
      endothelial cells against oxidative stress injury.
AB  - Endothelial cell injury and subsequent inflammation play pivotal roles in the
      pathogenesis of pulmonary fibrosis, a progressive and fatal disorder. We found
      previously that salvianolic acid B (SAB) attenuated experimental pulmonary
      fibrosis. Pulmonary fibrosis is driven by inflammation, but the anti-inflammatory
      role and mechanism of SAB on the treatment of pulmonary fibrosis is still
      unknown. Here, our in vivo studies showed that SAB had a strong anti-inflammatory
      effect on bleomycin-instilled mice by inhibiting inflammatory cell infiltration
      and inflammatory cytokine production. Moreover, SAB protected endothelial cells
      against oxidative stress injury and inhibited endothelial cell apoptosis in
      bleomycin-treated mice. The in vitro studies also showed that SAB decreased the
      H2O2-induced overproduction of reactive oxygen species to protect EA.hy926
      endothelial cells from oxidative damage, and further inhibited H2O2-induced
      permeability and overexpression of pro-inflammatory molecules. The next studies
      revealed that SAB inhibited the H2O2-induced cell apoptosis and attenuated the
      decrease of tight junction-related gene expression, resulting in a decrease of
      the endothelial permeability in injured endothelial cells. Furthermore, Western
      blot analysis suggested that SAB decreased endothelial cell permeability and
      expression of pro-inflammatory cytokines by inhibiting MAPK and NF-kappaB
      signaling pathways. Taken together, these data indicate that SAB exerted anti
      inflammatory roles in pulmonary fibrosis by protection of the endothelial cells
      against oxidative stress injury, mediated by inhibition of endothelial
      permeability and expression of pro-inflammatory cytokine via the MAPK and NF
      kappaB signaling pathways.

PMID- 30273544
TI  - Histone deacetylase 6 regulated expression of IL-8 is involved in the doxorubicin
      (Dox) resistance of osteosarcoma cells via modulating ABCB1 transcription.
AB  - Emerging evidence shows that cytokines such as interleukins (ILs) are involved in
      the progression and chemoresistance of multiple tumors, including osteosarcoma
      (OS). Our present study established the doxorubicin (Dox) resistant human OS MG
      63 and HOS cells and named them MG-63/Dox and HOS/Dox, respectively. The
      expression of IL-8, while not VEGFA, IL-32, or IL-34, was significantly increased
      in OS/Dox cells as compared with that in the parental cells. IL-8 neutralization
      antibody can significantly increase the Dox sensitivity of OS/Dox cells. Further,
      IL-8 can up regulate ABCB1, which encodes one important ATP-binding cassette
      (ABC) transporter /P-glycoprotein (P-gp). Mechanically, IL-8 increased the
      transcription of ABCB1 via up regulating its promoter activity, while had no
      effect on its protein or mRNA stability. Targeted inhibition of p65 can attenuate
      IL-8 induced transcription of ABCB1 in OS cells. Treatment OS cells with 5-aza
      dC, the inhibitor of DNMT, had no effect on expression of IL-8. Expression of
      HDAC6 in MG-63/Dox and HOS/Dox cells was significantly greater than that in their
      parental cells. Knockdown of HDAC6 can suppress the expression of IL-8 in OS
      cells. Collectively, our data showed that HDAC6 mediated upregulation of IL-8 can
      regulate the Dox sensitivity of OS cells via transcriptionally regulating the
      expression of ABCB1. Targeted inhibition of IL-8 might be a potent potential
      approach for overcome the Dox resistance of OS cells and helpful for clinical
      therapy of OS patients.

PMID- 30273545
TI  - Aldehyde dehydrogenase II rs671 polymorphism in essential hypertension.

PMID- 30273546
TI  - Physicochemical characterization of 6-O-acyl trehalose fatty acid monoesters in
      desiccated system.
AB  - The understanding of the basic physicochemical properties of trehalose lipid is
      indispensable to extending their availability. In this study, the hydrate crystal
      (Cr), the liquid crystalline (LC) phase and the glassy state formations of 6-O
      acyl trehalose fatty acid monoester (TREn) were examined under in a desiccated
      system. TREn (n = 10, 12, 14, 16) formed monohydrate Cr and showed the hydrate Cr
      glassy fluid lamellar LC (Lalpha) phase transition via dehydration in the heating
      process. Here, Lalpha phase for TRE10 and TRE12 was kinetically formed by the
      dehydration below the glass transition temperature (Tg). On the dehydration
      temperature (Tdeh), Tgs, and heat capacity changes (DeltaCps) at these Tgs, no
      distinct effects by the difference of the acyl chain length were recognized,
      possibly because the core structure of containing sugar hydrate Cr or sugar
      moieties should be similar regardless of the acyl chain length. Besides, TRE10
      having a relatively high hydrophilic/hydrophobic balance (HLB) afforded to form
      the cubic LC (Q) phase and the corresponding glassy phase, while TRE14 and TRE16
      having low HLB afforded the Lalpha phase as well as the corresponding glassy
      phases above Tg. TRE12 having middle HLB afforded both LCs and the corresponding
      glassy phase by controlling the kinetics of LC-LC phase transition between Lalpha
      and Q phases. Furthermore, the anomalous reversible phase transition during both
      the heating and cooling processes was also ascertained in the glassy phase for
      TRE16, which was considered the phase transition between glassy Lalpha and glassy
      lamellar gel (Lbeta) phase. It greatly empathizes the two-dimensional trehalose
      glass layer and fluid hydrocarbon chains in the TREn glassy phase. Thus, in this
      study, it was demonstrated that TREn as the simplest trehalose lipid exhibited
      the glassy formation performance as well as the hydrate Cr formation, which
      showed less chain length dependence, together with the LC formation and the phase
      transition between glassy Lalpha and glassy Lbeta phase, which depended on chain
      length greatly.

PMID- 30273547
TI  - The Clinical Application of Recombinant Human Bone Morphogenetic Protein 7 for
      Reconstruction of Alveolar Cleft: 10 Years' Follow-Up.
AB  - PURPOSE: The purpose of this study was to report on a 10-year assessment after
      the application of recombinant human bone morphogenetic protein 7 (rhBMP-7) for
      the reconstruction of alveolar clefts. PATIENTS AND METHODS: This study was
      conducted as a prospective phase II clinical trial on 9 unilateral and 2
      bilateral alveolar clefts that received rhBMP-7 (Osigraft; Stryker Biotech, UK).
      The mean age of the patients at surgery was 10.4 years. At 6 months
      postoperatively, occlusal radiographs were taken to evaluate bone formation at
      the cleft site. Patients were followed within the routine cleft care pathway for
      10 years to monitor the impact of bone morphogenetic protein 7 on orthodontic
      treatments and maxillary growth. Radiographs were taken according to the standard
      cleft care protocol. RESULTS: The radiographic assessment of the unilateral cleft
      lip and palate cases suggested good bone formation with a Kindelan score of grade
      1 or 2. The bilateral alveolar cleft cases had a score of grade 3 or 4,
      indicating failure or partial failure. The children with successful grafts
      underwent a routine orthodontic follow-up without incident. The maxillary growth
      appeared to be similar to that in cases grafted with autogenous bone. No long
      term complications and no abnormal pattern of bone formation were detected.
      CONCLUSIONS: The study provides unique evidence on the long-term safety of rhBMP
      7 when applied at the area of skeletal immaturity for the reconstruction of
      alveolar clefts in children.

PMID- 30273548
TI  - Extraordinary Contributions to Disability and Rehabilitation Research and
      Unwavering Leadership: A Tribute to Ruth Brannon.

PMID- 30273549
TI  - Economic Evaluation of Activities of Daily Living Retraining During Posttraumatic
      Amnesia for Inpatient Rehabilitation Following Severe Traumatic Brain Injury.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of structured activities of daily
      living (ADL) retraining during posttraumatic amnesia (PTA) plus treatment as
      usual (TAU) vs TAU alone for inpatient rehabilitation following severe traumatic
      brain injury (TBI). DESIGN: Trial-based economic evaluation from a health-system
      perspective. SETTING: Inpatient rehabilitation center. PARTICIPANTS: Participants
      (N=104) admitted to rehabilitation and in PTA for >7 days following severe TBI.
      INTERVENTIONS: Structured ADL retraining during PTA plus TAU vs TAU alone.
      Structured ADL retraining was manualized to minimize the risk of agitation and
      maximize functional improvement, following principles of errorless and procedural
      learning and targeting individualized therapy goals. TAU included physiotherapy
      and/or speech therapy during PTA plus ADL retraining after PTA emergence. MAIN
      OUTCOME MEASURES: FIM total scores at baseline, PTA emergence, hospital
      discharge, or final follow-up (2mo postdischarge) where FIM total scores were
      calculated as the sum of 5 FIM motor self-care items and a FIM meal-preparation
      item. RESULTS: Structured ADL retraining during PTA significantly increased
      functional independence at PTA emergence (mean difference: 4.90, SE: 1.4, 95%
      confidence interval [CI]: 1.5, 8.3) and hospital discharge (mean difference:
      5.22, SE: 1.4, 95% CI: 1.8, 8.7). Even in our most pessimistic scenario,
      structured ADL retraining was cost-saving as compared to TAU (mean: -$7762; 95%
      CI: -$8105, -$7419). Together, these results imply that structured ADL retraining
      dominates (less costly but no less effective) TAU when effectiveness is evaluated
      at PTA emergence and hospital discharge. CONCLUSIONS: Structured ADL retraining
      during PTA yields net cost-savings to the health system and offers a cost
      effective means of increasing functional independence at PTA emergence and
      hospital discharge.

PMID- 30273550
TI  - Neuroprotective effects of MHY908, a PPAR alpha/gamma dual agonist, in a MPTP
      induced Parkinson's disease model.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and are
      considered promising therapeutic targets in several neurodegenerative diseases. A
      number of PPAR agonists have been shown to have neuroprotective properties in the
      presence of oxidative stress, neuroinflammatory response, and apoptosis in
      various neurodegenerative disease. MHY908 is a novel PPAR alpha/gamma dual
      agonist, which has been shown to suppress inflammatory response and attenuate
      insulin resistance in aged rats and db/db mice. Here, we evaluated the
      neuroprotective effects of MHY908 in a 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-induced mouse model of PD. Pretreatment with MHY908
      attenuated MPTP-induced dopaminergic neuronal loss and motor deficit. MPTP
      induced glial activations were mitigated by MHY908 in the nigrostriatal pathway,
      and MHY908 effectively blocked 1-methyl-4-phenylpyridinium (MPP+)-induced cell
      death and ROS production in SH-SY5Y neuroblastoma cells. Further study revealed
      MHY908 inhibited MPP+-induced astroglial activation by suppressing NF-kappaB
      signaling in primary astrocytes. Taken together, the present study suggests that
      PPAR alpha/gamma dual agonists be considered potentially useful preventions for
      PD and other neurodegenerative diseases associated with neuroinflammation.

PMID- 30273551
TI  - TRPM2 confers susceptibility to social stress but is essential for behavioral
      flexibility.
AB  - Transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable,
      nonselective cation channel and a member of the TRP channel superfamily that acts
      as a sensor of intracellular redox states. TRPM2 is widely distributed in many
      tissues and highly expressed in the brain, but the physiological roles of TRPM2
      in the central nervous system remain unclear. In this study, TRPM2-deficient mice
      were examined in a series of behavioral tests. TRPM2-deficient mice did not
      significantly differ from wild-type littermates in muscle strength, light/dark
      transition test, rotarod, elevated plus maze, social interaction, prepulse
      inhibition, Y-maze, forced swim test, cued and contextual fear conditioning, and
      tail suspension test. In the Barnes circular maze, TRPM2-deficient mice learned
      the fixed escape box position at similar extent to wild-type littermates,
      suggesting normal reference memory. However, performance of the first reversal
      trial and probe test were significantly impaired in TRPM2-deficient mice. In the
      T-maze delayed alternation task, TRPM2 deficiency significantly reduced choice
      accuracy. These results indicate that TRPM2-deficient mice shows behavioral
      inflexibility. Meanwhile, social avoidance induced by repeated social defeat
      stress was significantly attenuated in TRPM2-deficient mice, suggesting that
      TRPM2 deficiency confers stress resiliency. Our findings indicate that TRPM2
      plays an essential role in maintaining behavioral flexibility but it increases
      susceptibility to stress.

PMID- 30273552
TI  - Alzheimer's disease (AD) therapeutics - 2: Beyond amyloid - Re-defining AD and
      its causality to discover effective therapeutics.
AB  - Compounds targeted for the treatment of Alzheimer's Disease (AD) have
      consistently failed in clinical trials despite evidence for target engagement and
      pharmacodynamic activity. This questions the relevance of compounds acting at
      current AD drug targets - the majority of which reflect the seminal amyloid and,
      to a far lesser extent, tau hypotheses - and limitations in understanding AD
      causality as distinct from general dementia. The preeminence of amyloid and tau
      led to many alternative approaches to AD therapeutics being ignored or
      underfunded to the extent that their causal versus contributory role in AD
      remains unknown. These include: neuronal network dysfunction; cerebrovascular
      disease; chronic, local or systemic inflammation involving the innate immune
      system; infectious agents including herpes virus and prion proteins; neurotoxic
      protein accumulation associated with sleep deprivation, circadian rhythm and
      glymphatic/meningeal lymphatic system and blood-brain-barrier dysfunction;
      metabolic related diseases including diabetes, obesity hypertension and
      hypocholesterolemia; mitochondrial dysfunction and environmental factors. As AD
      has become increasingly recognized as a multifactorial syndrome, a single
      treatment paradigm is unlikely to work in all patients. However, the biomarkers
      required to diagnose patients and parse them into mechanism/disease-based sub
      groups remain rudimentary and unvalidated as do non-amyloid, non-tau
      translational animal models. The social and economic impact of AD is also
      discussed in the context of new FDA regulatory draft guidance and a proposed
      biomarker-based Framework (re)-defining AD and its stages as part of the larger
      landscape of treating dementia via the 2013 G8 initiative to identify a disease
      modifying therapy for dementia/AD by 2025.

PMID- 30273553
TI  - Alzheimer's disease (AD) therapeutics - 1: Repeated clinical failures continue to
      question the amyloid hypothesis of AD and the current understanding of AD
      causality.
AB  - Deposits of amyloid plaques and neurofibrillary tangles of aggregated tau in the
      brain represent key hallmarks of the neurodegenerative disorder, Alzheimer's
      Disease (AD) and form the basis of the major hypotheses of AD causality. To date,
      therapeutics that reduce brain amyloid in AD patients have demonstrated no effect
      in reversing the associated decline in cognition or function indicating that the
      amyloid hypothesis is either incorrect or that there is a point when the disease
      becomes independent of Abeta production or is refractory to any type of
      therapeutic intervention. The clinical failures of inhibitors of tau aggregation,
      neurotransmitter modulators and drugs repurposed from AD-associated disease
      indications tend to support this latter viewpoint. Current understanding of AD
      causality is thus incomplete, a situation that has been compounded by a debate on
      whether AD is a singularly distinct form of dementia and by the dogmatic
      promotion of hypotheses over actual clinical data. The latter has repeatedly led
      to compounds lacking efficacy in Phase II trials being advanced into Phase III
      where their lack of efficacy is routinely recapitulated. This Commentary, the
      first of two, discusses amyloid and tau as putative drug targets for AD in the
      context of the prevalence and economic and social impact of this insidious
      neurodegenerative disease.

PMID- 30273554
TI  - How much starvation, desiccation and oxygen depletion can Drosophila melanogaster
      tolerate before its upper thermal limits are affected?
AB  - Heat tolerance is commonly assessed as the critical thermal maximum (CTmax) using
      the dynamic method exposing organisms to a gradually increasing (ramping)
      temperature until organisms fall into a coma. The CTmax estimate is dependent on
      the ramping rate, with decreased rates leading to longer treatments and
      ultimately lower CTmax estimates. There is a current discussion surrounding the
      physiological dynamics of the effect of the time of exposure by temperature
      interaction on these estimates. Besides temperature the time of exposure to
      limited food (starvation), desiccation, and reduced levels of oxygen or increased
      levels of CO2 may, in interaction with ramping rate, act as confounding factors
      when assessing upper thermal limits using the dynamic method. Here we test the
      role of the different potentially confounding factors for assaying thermal
      tolerance using a ramping assay under four different ramping rates, varying from
      0.01  degrees C/min to 0.2  degrees C/min. We find that CTmax values are higher
      at faster ramping rates and that oxygen or CO2 concentration does not show any
      negative effect on the CTmax values obtained within the experimental pre
      treatment period (32 h). Both water (up to 6 h) and food (up to 42 h) deprivation
      prior to assay showed a negative correlation with thermal tolerance of the flies.
      For both traits, we found a significant interaction with ramping rate, most
      likely due to prolonged assays at lower rates. However, as little water was lost
      during the ramping assay and as food deprivation only modestly affected CTmax
      values, results were very robust to the conditions experienced during the assay
      (even at slow rates) and mainly affected by the conditions experienced prior to
      performing the assay. Thus, for the most commonly applied experimental conditions
      CTmax estimates are unlikely to be biased or confounded by ramping rate,
      starvation, desiccation or deteriorating atmospheric composition.

PMID- 30273555
TI  - Pilot Tobacco Treatment Intervention for Women in Residential Treatment for
      Substance Use Disorder.
AB  - OBJECTIVE: To test the feasibility, acceptability, and efficacy of Get Fit and
      Quit (GFAQ), a community-engaged, holistic tobacco treatment program for women of
      childbearing age in a residential substance use disorder treatment facility.
      DESIGN: A quasi-experimental, one-group, longitudinal design. SETTING: A local
      Young Men's Christian Association (YMCA) location. PARTICIPANTS: Twenty-three
      women of childbearing age were enrolled in the study. Nearly all (21/23)
      participants were White, and most were nonpartnered and unemployed. More than one
      third of participants had more than high school educations, and five (22%) were
      pregnant at enrollment. METHODS: The program was conducted in 10 sessions over 6
      months. For each 90-minute session, approximately 45 minutes were dedicated to
      smoking cessation, and 45 minutes were dedicated to group physical activity.
      Means and 95% confidence intervals were used to summarize nicotine dependence,
      expired carbon monoxide, urine cotinine, and exercise self-efficacy at baseline
      and 5-week, 8-week, and 6-month assessments. Cigarettes smoked per day were
      summarized using medians and interquartile ranges over time. Program satisfaction
      and regular exercise were presented as percentages with 95% confidence intervals.
      RESULTS: Of the 23 women who enrolled in GFAQ, 7 (30%) completed the program.
      Compared with baseline results, participants who completed GFAQ had lower
      nicotine dependence and smoked fewer cigarettes per day. Additionally, at 5
      weeks, more GFAQ participants exercised regularly (64%) compared with baseline
      (14%). Most participants viewed the program favorably. CONCLUSION: Smoking in
      women of childbearing age with substance use disorders is an important public
      health issue. GFAQ is a promising intervention for tobacco treatment for this
      high-risk population, although the number of initial participants who completed
      the program was low.

PMID- 30273556
TI  - A highly selective and sensitive fluorescent sensor for relay recognition of Zn2+
      and HSO4-/H2PO4- with "on-off" fluorescent responses.
AB  - A simple and effective fluorescent sensor bearing pyridine units was designed and
      synthesized. The sensor can detect Zn2+ with high selectivity accompanied by a
      distinct fluorescence turn-on response, inducing the fluorescent color markedly
      changed from darkness to bright green. The limit of detection (LOD) was
      calculated as 8.56 * 10-9 M with a good linearity (R = 0.95943). In addition, the
      chelate of sensor with Zn2+ can further recognize H2PO4-/HSO4- with notable
      fluorescence quenching behaviors over other anions and the LODs were as low as
      3.44 * 10-6 M (R = 0.99762) and 3.84 * 10-6 M (R = 0.99315), respectively.

PMID- 30273557
TI  - Development and characterization of sandwich-type enzyme-linked aptamer assay for
      the detection of rongalite in food.
AB  - Rongalite is an essentially strong carcinogen, which due to its properties as a
      bleaching and brightening, is illegally added to the food processing. In this
      study, a sandwich-type enzyme-linked aptamer assay (ELAA) is developed by using a
      rongalite-specific aptamer G02 modified fluorescein amidite (FAM) as a capture
      probe and aptamer C01 modified biotin as a signal element. In the presence of
      rongalite, the aptamer G02-rongalite-aptamer C01 complex is produced, and the
      absorbance value can be subsequently measured. The sandwich-type ELAA was shown
      to detect rongalite with high specificity and affinity, with a KD value of 19.91
      +/- 1.321 nM. In addition, the standard curve was established, with the limit of
      quantification (LOQ) for rongalite at 10 ng mL-1. By calculating the slope of the
      standard curve and the standard deviation of the blank values, the method
      detection limit (MDL) was 0.572 ng mL-1. Additionally, the accuracy of the
      sandwich-type ELAA was demonstrated in real food samples. Compared with high
      pressure liquid chromatography (HPLC) assay, the sandwich-type ELAA can detect
      rongalite directly, and it has great advantages in pre-treatment, operation
      technique and cost. In short, our data suggest that the sandwich-type ELAA may be
      applicable as a molecular detection technique for rongalite.

PMID- 30273558
TI  - Distinct patterns of atrial electrical and structural remodeling in angiotensin
      II mediated atrial fibrillation.
AB  - Atrial fibrillation (AF) is prevalent in hypertension and elevated angiotensin II
      (Ang II); however, the mechanisms by which Ang II leads to AF are poorly
      understood. Here, we investigated the basis for this in mice treated with Ang II
      or saline for 3 weeks. Ang II treatment increased susceptibility to AF compared
      to saline controls in association with increases in P wave duration and atrial
      effective refractory period, as well as reductions in right and left atrial
      conduction velocity. Patch-clamp studies demonstrate that action potential (AP)
      duration was prolonged in right atrial myocytes from Ang II treated mice in
      association with a reduction in repolarizing K+ currents. In contrast, APs in
      left atrial myocytes from Ang II treated mice showed reductions in upstroke
      velocity and overshoot, as well as greater prolongations in AP duration. Ang II
      reduced Na+ current (INa) in the left, but not the right atrium. This reduction
      in INa was reversible following inhibition of protein kinase C (PKC) and PKCalpha
      expression was increased selectively in the left atrium in Ang II treated mice.
      The transient outward K+ current (Ito) showed larger reductions in the left
      atrium in association with a shift in the voltage dependence of activation.
      Finally, Ang II caused fibrosis throughout the atria in association with changes
      in collagen expression and regulators of the extracellular matrix. This study
      demonstrates that hypertension and elevated Ang II cause distinct patterns of
      electrical and structural remodeling in the right and left atria that
      collectively create a substrate for AF.

PMID- 30273559
TI  - Epithelial RNase H2 Maintains Genome Integrity and Prevents Intestinal
      Tumorigenesis in Mice.
AB  - BACKGROUND & AIMS: RNase H2 is a holoenzyme, composed of 3 subunits (ribonuclease
      H2 subunits A, B, and C), that cleaves RNA:DNA hybrids and removes mis
      incorporated ribonucleotides from genomic DNA through ribonucleotide excision
      repair. Ribonucleotide incorporation by eukaryotic DNA polymerases occurs during
      every round of genome duplication and produces the most frequent type of
      naturally occurring DNA lesion. We investigated whether intestinal epithelial
      proliferation requires RNase H2 function and whether RNase H2 activity is
      disrupted during intestinal carcinogenesis. METHODS: We generated mice with
      epithelial-specific deletion of ribonuclease H2 subunit B (H2bDeltaIEC) and mice
      that also had deletion of tumor-suppressor protein p53 (H2b/p53DeltaIEC); we
      compared phenotypes with those of littermate H2bfl/fl or H2b/p53fl/fl (control)
      mice at young and old ages. Intestinal tissues were collected and analyzed by
      histology. We isolated epithelial cells, generated intestinal organoids, and
      performed RNA sequence analyses. Mutation signatures of spontaneous tumors from
      H2b/p53DeltaIEC mice were characterized by exome sequencing. We collected
      colorectal tumor specimens from 467 patients, measured levels of ribonuclease H2
      subunit B, and associated these with patient survival times and transcriptome
      data. RESULTS: The H2bDeltaIEC mice had DNA damage to intestinal epithelial cells
      and proliferative exhaustion of the intestinal stem cell compartment compared
      with controls and H2b/p53DeltaIEC mice. However, H2b/p53DeltaIEC mice
      spontaneously developed small intestine and colon carcinomas. DNA from these
      tumors contained T>G base substitutions at GTG trinucleotides. Analyses of
      transcriptomes of human colorectal tumors associated lower levels of RNase H2
      with shorter survival times. CONCLUSIONS: In analyses of mice with disruption of
      the ribonuclease H2 subunit B gene and colorectal tumors from patients, we
      provide evidence that RNase H2 functions as a colorectal tumor suppressor.
      H2b/p53DeltaIEC mice can be used to study the roles of RNase H2 in tissue
      specific carcinogenesis.

PMID- 30273561
TI  - Modeling Glucose Transport From Systemic Circulation to Sweat.
AB  - Sweat sensing may provide a noninvasive means of estimating blood biomarker
      levels if a number of technological hurdles can be overcome. This report
      describes progress on a physiologically based transport model relating sweat
      glucose and key electrolyte concentrations to those in blood. Iontophoretically
      stimulated sweat glucose and fasted blood glucose were simultaneously measured in
      2 healthy human subjects. Sweat glucose was measured with a novel, prototype skin
      sweat collection/analysis system and blood glucose with a commercial fingerstick
      glucometer. These data, in combination with data from 3 published studies, were
      used to calibrate a dynamic mathematical model for glucose transport and uptake
      in human skin, followed by extraction into sweat. Model simulations revealed that
      experimental and literature sweat glucose values were well represented under
      varying physiologic conditions. The glucose model, calibrated under a variety of
      experimental conditions including electrical enhancement, revealed a 10 min blood
      to-sweat lag time and a sweat/blood glucose level ranging from 0.001 to 0.02,
      depending on the sweat rate. These values are consistent with those reported in
      the literature. The developed model satisfactorily described the sweat-to-blood
      relationship for glucose concentrations measured under different conditions in 4
      human studies including the present pilot study. The algorithm may be used to
      facilitate sweat biosensor development.

PMID- 30273560
TI  - Increased sleep time and reduced energy expenditure contribute to obesity after
      ovariectomy and a high fat diet.
AB  - In this study we examined if sleep time, caloric intake and energy expenditure
      are important contributors to development of ovariectomy-induced obesity in mice
      fed control or high fat diet (HFD). Twelve female mice at 6 weeks of age were
      divided into 2 groups: Sham (n = 5) and ovariectomized (OVX, n = 7). Mice were
      fed control diet for 9 weeks and shifted to HFD for additional 9 weeks. Food
      intake and body weight were measured daily and body composition was measured
      weekly by EchoMRI. Energy expenditure (EE), oxygen consumption (VO2), motor
      activity (MA) and sleep time were monitored at week 9 during control diet and
      HFD. OVX did not alter caloric intake, body weight or body composition, MA, sleep
      time or fasting blood glucose, but slightly reduced EE compared to Sham mice on
      control diet. After HFD feeding, OXV mice had similar caloric intake, lean mass,
      MA, and blood glucose levels but had significantly greater weight gain (8.2 +/-
      1.0 vs. 4.8 +/- 1.2 g, p < 0.05), increased fat mass and sleep time, and reduced
      EE (3.3 +/- 0.4 vs. 5.5 +/- 0.2 kcal/h) and VO2 (1.12 +/- 0.01 vs. 1.83 +/- 0.05
      ml/min) compared to Sham group. Daytime blood pressure was higher while nighttime
      heart rate was lower in OVX group. These results suggest that OVX may not
      substantially alter body weight or body composition in mice fed a normal diet,
      but when combined with HFD it increases sleep time and reduces EE, leading to
      greater weight gain and adiposity without altering food intake.

PMID- 30273562
TI  - Gene expression profile of cytokines produced in biopsies from patients with
      American cutaneous leishmaniasis.
AB  - American cutaneous leishmaniasis (ACL) causes a local inflammatory process,
      inducing expression of several cytokine genes. Particularly, IFN-gamma can
      predict to disease susceptibility. Based in these data, this study was aimed to
      investigate the gene expression profile of IFN-gamma, IL-10, IL-27, TNF-gamma,
      TGF-beta and IL-6 produced in biopsies from ACL patients; and whether the gene
      expression profile of IFN-gamma could determine the disease evolution. Gene
      expression of 6 cytokines was investigated in 40 formalin-fixed paraffin embedded
      (FFPE) biopsies from patients with cutaneous leishmaniosis (CL); and 10 FFPE
      biopsies from patients with mucosal leishmaniasis (ML) (control). All 50 patients
      were infected with Leishmania (Viannia) braziliensis. Gene expression was
      determined by qPCR; and a normal control group was used for calculations (5
      normal biopsies). Values were expressed as Relative Quantification (RQ). The 40
      CL patients were classified into 2 groups. CLlowIFN-gamma, 35 patients with RQ
      for IFN-gamma below 100; and CLhighIFN-gamma, 5 (12.5%) patients with RQ above
      100. Significant increase of mRNA levels of IFN-gamma, IL-10 and IL-27 was shown
      in CLhighIFN-gamma group when compared with CLlowIFN-gamma and ML groups. TNF
      alpha levels in CLlowIFN-gamma group were higher than CLhighIFN-gamma and ML
      groups. TGF-beta and IL-6 were similar in 3 groups. Comparison of cytokine
      expression/group showed that CLlowIFN-gamma group had an equilibrium between the
      cytokines analyzed. In ML group, IFN-gamma was over-expressed; but in CLhighIFN
      gamma group, besides IFN-gamma, IL-27 was also over-expressed. The immune
      response to Leishmania induces to identification of some markers, which can be
      determined by analysis by gene expression of cytokines produced in biopsies.

PMID- 30273563
TI  - Echinostoma revolutum: Development of a high performance DNA-specific primer to
      demonstrate the epidemiological situations of their intermediate hosts.
AB  - Echinostomiasis caused by the Echinostoma group, in particular E. revolutum are a
      significant problem for both humans and other animals. This group has a large
      number of morphological similarities that are difficult and time-consuming to
      identify. The present study aimed to develop high-performance tools for the
      detection of the prevalence of E. revolutum and to reveal the prevalence of E.
      revolutum infections in intermediate snail hosts in Lopburi province, Thailand.
      The snail specimens were collected by stratified sampling method and examined to
      collect trematodes in the larval stage. The specific primer was manually designed
      and based on 18 s rDNA and verified the specificity and sensitivity for use as an
      identification tool to compare with classical method, constructed by epidemic
      mapping. The overall prevalence value of E. revolutum was found to be 16.26%. Tha
      Luang district had the highest prevalence (70.14%), followed by Chai Badan,
      Phatthana Nikhom, Tha Wung, Ban Mi, Khok Samrong, Nong Muang and Sa Bot at 42%,
      25.14%, 2.52%, 1.73%, 2%, 1.33% and 0.40%, respectively. With regard to the
      specific primer, it can amplify both cercarial and metacercarial DNA (90 pg/MUl.)
      and discriminated E. revolutum from its hosts, other trematodes and other
      echinostome larvae with no cross-reactions. Therefore, the developed specific
      primer can be used as a species-specific identification tool with a high degree
      of sensitivity and specificity. Consequently, this data is important for
      monitoring the outbreak of E. revolutum. It can be applied for initiating
      surveillance programs of snail-borne diseases in both medical and veterinary
      studies.

PMID- 30273564
TI  - Titanium dioxide nanoparticles induce proteostasis disruption and autophagy in
      human trophoblast cells.
AB  - Titanium dioxide nanoparticles (TiO2 NPs) exist in many nano-products and
      concerns have been raised about their potential toxicity on human beings. One
      such issue is their potential effects on placental function, and the studies on
      this topic are limited and the mechanism remains unclear. Here we employed human
      trophoblast HTR-8/SVneo cells to investigate the effects of TiO2 NPs on
      trophoblast. Results showed that TiO2 NPs could enter cells and were mostly
      distributed in lysosomes, with some in the cytoplasm. TiO2 NPs and protein
      aggregation were found in both fetal bovine serum (FBS) in culture medium and
      cytoplasm of HTR-8/SVneo cells. In consistence with that, proteostasis of HTR
      8/SVneo cells was significantly disrupted and endoplasmic reticulum (ER) stress
      related markers including PERK, IRE1-alpha were increased. After high speed
      centrifugation, the proteins PERK and IRE1-alpha were dramatically decreased in
      the highest TiO2 NPs treatment group, which indicated interactions between TiO2
      NPs and these two proteins. Meanwhile, the protein expressions of LC3-II/LC3-I
      and P62, the autophagy biomarkers, were increased and the autophagy flux was not
      blocked. Cellular ROS stress increased and mitophagy related genes including PINK
      and Parkin increased along with the increased co-localization of LC3 and
      mitochondria. Taken together, these results indicated that TiO2 NPs interacted
      with intracellular proteins and activated ER stress and mitophagy in HTR-8/SVneo
      cells, which might do damage to placental function.

PMID- 30273565
TI  - Investigation of genotoxic and apoptotic effects of zirconium oxide nanoparticles
      (20 nm) on L929 mouse fibroblast cell line.
AB  - In recent years, advances in nano-scale technology have led to the use of
      nanoparticles in almost all areas of life. Nanoparticles (NP) have been
      acknowledged as one of the emerging environmental threats; however, studies in
      different components of environment are limited. Among the available
      nanoparticles, zirconium oxide nanoparticles are widely used in tooth coating and
      cosmetic products. In this study, three different concentrations of 20 nM
      Zirconium Oxide nanoparticles were used to investigate the genotoxic and
      apoptotic effects in vitro conditions by single cell gel electrophoresis (Comet)
      and flow cytometry methods on L929 Mouse Fibroblast cell line. In this study, we
      aimed to decipher whether Zirconium Oxide nanoparticles had genotoxic and
      apoptotic effects on fibroblast cells or not. The relationship between the
      apoptotic effect and the genotoxic effect was examined. Three different
      concentrations (50 MUg/ml, 100 MUg/ml and 150 MUg/ml) of 20 nM Zirconium Oxide
      nanoparticles were used on L929 cells in order to determine the relationship
      between apoptotic and genotoxic parameters. Our results support that Zirconium
      Oxide nanoparticles induced DNA damage and apoptosis at all used concentrations.
      In vivo studies are currently conducted to further evaluate the cytotoxic effect
      of these nanoparticles.

PMID- 30273566
TI  - Salinomycin suppresses cancer cell stemness and attenuates TGF-beta-induced
      epithelial-mesenchymal transition of renal cell carcinoma cells.
AB  - Metastatic Renal cell carcinoma (RCC) remains a difficult oncologic challenge.
      Salinomycin is a monocarboxylic polyether antibiotic, which has been proved to
      possess anti-tumor activities in multiple types of cancer cells. However, its
      effects on RCC cells remains unclear. In our study, salinomycin could inhibit the
      proliferation and viability of RCC cell lines 786-O and ACHN. The TUNEL assay
      revealed that treatment with salinomycin induced DNA breaking in RCC cells.
      Consistently, Western blotting showed up-regulation of pro-apoptotic biomarkers
      (cleaved caspase3/9 and cleaved PARP1) and down-regulation of anti-apoptotic
      biomarker (survivin) in RCC cells after salinomycin treatment, suggesting that
      salinomycin could induce RCC cell apoptosis. salinomycin treatment also
      suppressed the sphere formation ability of RCC cells and decreased the
      expressions of CD105, ALDH1 and CD44, biomarkers for reflecting the stemness of
      RCC cells. salinomycin treatment effectively down-regulated SMO and Gli1, two key
      proteins in Hedghog signaling pathway, in a dose-dependent manner. Moreover,
      salinomycin could suppress the invasion and migration of RCC cells in the
      presence of TGF-beta1, as observed in wound-healing and Transwell assays.
      salinomycin treatment attenuated TGF-beta1-induced epithelial-mesenchymal
      transition (EMT), as evidenced by its ability to increase E-cadherin expression
      and decrease N-cadherin, Snail and MMP-2 expressions in RCC cells. Finally,
      salinomycin inhibited the tumorigenecity of RCC cells in vivo. Our study provides
      the evidence that salinomycin possess multiple anti-tumor activities against RCC,
      as it, in particular, suppressed the cancer stem cell properties and attenuated
      TGF-beta-induced EMT. Therefore, it may serve as a potentially therapeutic
      candidate for metastatic RCC and improve the prognosis of RCC patients.

PMID- 30273567
TI  - Perioperative Echocardiographic Index of Left Ventricular Filling Pressure in
      Cardiac Surgery.
AB  - BACKGROUND: The elevated preoperative ratio of early transmitral flow velocity to
      early diastolic velocity of the mitral annulus (E/e') as an echocardiographic
      index of left ventricular filling pressure is known to be associated with poor
      postoperative outcomes. We investigated the association between preoperative and
      postoperative E/e' elevation and clinical outcomes after cardiac operations.
      METHODS: The study divided 1,353 patients who underwent cardiac operations into
      four groups: preoperative and postoperative E/e' <=15 (low-low), preoperative
      E/e' <=15 but postoperative E/e' >15 (low-high), preoperative E/e' >15 but
      postoperative E/e' <=15 (high-low), and preoperative and postoperative E/e' >15
      (high-high). Cox proportional hazard analysis was performed. Kaplan-Meier curve
      analysis was performed before and after propensity score matching. RESULTS: The
      four perioperative E/e' categories were independently associated with 5-year
      mortality (hazard ratio, high-high vs low-low: 3.58; low-high vs low-low: 3.75;
      high-low vs low-low: 1.18). Kaplan-Meier curves showed that mortality was
      significantly different between the groups (log-rank test: high-high vs. low-low,
      p < 0.001; low-high vs low-low, p < 0.001). Postoperative intensive care unit and
      hospital lengths of stay, incidence of acute kidney injury, and 1-year mortality
      were significantly different. However, after propensity score matching, mortality
      and the incidence of postoperative acute kidney injury were significantly
      different only between postoperative E/e' <=15 and E/e' >15, but not between
      preoperative E/e' <=15 and E/e' >15. CONCLUSIONS: Postoperative E/e' >15 was more
      strongly associated with mortality and acute kidney injury than preoperative E/e'
      >15. Measurement of the postoperative E/e' ratio may help in assessing the risk
      of these patients.

PMID- 30273568
TI  - Off-Pump Versus On-Pump Impact: Diabetic Patient 5-Year Coronary Artery Bypass
      Clinical Outcomes.
AB  - BACKGROUND: For diabetic patients who require coronary artery bypass graft (CABG)
      operation, controversy persists whether an off-pump or an on-pump approach may be
      advantageous. This US-based, multicenter, randomized, controlled trial,
      Department of Veterans Affairs Randomization On versus Off Bypass Follow-up
      Study, compared diabetic patients' 5-year clinical outcomes for off-pump versus
      on-pump procedures. METHODS: From 2002 to 2008, 835 medically treated (ie, oral
      hypoglycemic agent or insulin) diabetic patients underwent either off-pump (n =
      402) or on-pump (n = 433) CABG. Five-year primary end points included all-cause
      death and major adverse cardiovascular events (MACE; composite included all-cause
      death, myocardial infarction, or repeat revascularization). Secondary 5-year end
      points included cardiac death and MACE-related components. With baseline risk
      factors balanced, outcomes were evaluated by using a p value less than or equal
      to 0.01; nonsignificant trends were reported for p values greater than 0.01 and
      less than or equal to 0.15. RESULTS: Five-year all-cause death rates were 20.2%
      off pump versus 14.1% on pump (p = 0.0198). No differences were seen in MACE
      (32.6% off-pump approach versus 28.6% on-pump approach, p = 0.216), repeat
      revascularization (12.4% off-pump approach versus 11.8% on-pump approach, p =
      0.770), and nonfatal myocardial infarction (12.7% off-pump approach versus 10.4%
      on-pump approach, p = 0.299). Cardiac death trended worse with off-pump CABG
      (9.0%) than with on-pump CABG (6.25%, p = 0.137). Sensitivity analyses that
      removed conversions confirmed these findings. CONCLUSIONS: With a 6.1% absolute
      difference, a strong trend toward improved 5-year survival was observed with on
      pump CABG for medically treated diabetic patients. No off-pump advantage was
      found for any 5-year end points. A future clinical trial now appears warranted to
      rigorously compare off-pump versus on-pump longer term outcomes for diabetic
      patients.

PMID- 30273569
TI  - Costs Five Years After Off-Pump or On-Pump Coronary Artery Bypass Surgery.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) is a common surgical treatment
      for ischemic heart disease. Little is known about the long-term costs of
      conducting the surgery on-pump or off-pump. METHODS: As part of the Randomized
      On/Off Bypass follow-up study, we followed 2,203 participants randomized to on
      pump (n = 1,099) and off-pump (n = 1,104) CABG for 5 years using Department of
      Veterans Affairs and Medicare administrative data. We examined annual costs
      through 5 years, standardized to 2016 dollars, using multivariate regression
      models, controlling for site and baseline patient factors. RESULTS: In the first
      year, including the CABG surgery, annual average costs were $66,599 (SE, $1,946)
      for the on-pump group and $70,552 (SE, $1,954) for the off-pump group. In years 2
      to 5, average costs ranged from $15,000 to $20,000 per year. There was no
      significant difference between on-pump and off-pump across the 5 years. We
      explored differences among high-risk subgroups (diabetes, chronic obstructive
      pulmonary disease, peripheral vascular disease, cerebrovascular disease, renal
      dysfunction, ejection fraction < 35%, over age 70 years), and found no treatment
      assignment by time interactions, except for a nonsignificant trend in patients
      with diabetes. CONCLUSIONS: At 5 years, the average costs of off-pump and on-pump
      CABG patients did not statistically differ. Costs do not favor one approach and
      the decision should be based on clinical risks, especially in subgroups. Future
      research is warranted to examine post-CABG costs and outcomes for diabetic
      patients over time.

PMID- 30273570
TI  - Intra-Extra Cardiac Versus Extracardiac Fontan Modifications: Comparison of Early
      Outcomes.
AB  - BACKGROUND: Intra-extracardiac (IE) Fontan modification has advantages over the
      lateral tunnel modification. A direct comparison of Intra-extracardiac (IE) to
      the Extracardiac (EC) modification so far has not been done. This study aims to
      compare IE to EC Fontan, with respect to early postoperative outcomes. METHODS:
      We retrospectively compared outcomes of the Fontan operation using either the
      Intra-extracardiac (IE) or Extracardiac (EC) conduit modification between January
      2012 and December 2016. IE and EC groups were compared using univariate and
      multivariable regression analysis. To eliminate the confounding effects of
      fenestration, repeat intergroup comparison was performed after excluding non
      fenestrated patients. RESULTS: 81 patients were grouped according to Fontan
      modification into IE group (n=43) and EC group ( n=38). The Fontan was
      fenestrated in 100% of IE group compared to only 55% of EC group (p<0.001).
      Cardiopulmonary bypass time was shorter for the IE group (74 vs. 103, p<0.001)
      The IE patients had median cross clamp time of 34 minutes, while the EC group
      required cross clamping only in 2 cases (35, 95 minutes) (p<0.001). IE group had
      significantly shorter median duration of pleural effusion (8 days vs. 11 days,
      p=0.007) and hospital length of stay (9 days vs. 13 days, p=0.001) than the EC
      group. Multivariable linear regression analysis revealed that IE modification
      independently associated with reduced duration of pleural effusion (p=0.004) and
      hospital LOS (p=0.003). Presence of any unfavorable hemodynamics on preoperative
      assessment was also associated with longer duration of pleural effusion and
      hospital LOS for patients with fenestration. CONCLUSIONS: IE Fontan modification
      may be associated with reduced duration of postoperative pleural effusion and
      hospital length of stay compared to EC modification.

PMID- 30273572
TI  - Intensity of Glycemic Control Affects Long-Term Survival After Coronary Artery
      Bypass Graft Surgery.
AB  - BACKGROUND: A patient's HbA1c, regardless of diabetic status, is a measure of
      glycemic control. Studies have found it to be an independent predictor of short
      term mortality in patients undergoing CABG. In this study, we used pre-operative
      HbA1c to assess if levels are associated with short- and long-term survival after
      CABG. METHODS: From a regional registry of consecutive cases we identified a
      cohort of 6,415 patients undergoing on-pump, isolated CABG from 2008-2015 with
      documented pre-operative HbA1c level. We defined four HbA1c groups: <5.7
      (N=1,713); 5.7-6.4 (N=2,505); 6.5-8.0 (N=1,377); >8 (N=820). Relationship to in
      hospital outcomes and long-term survival was assessed. Outcome rates and hazard
      ratios (HR) were adjusted for patient and disease risk factors using
      multivariable logistic regression and Cox models. RESULTS: The study included
      3,740 patients (58%) not diagnosed as diabetic and 2,674 diabetics. Fifty-two
      percent (1933) of non-diabetics were pre-diabetics (5.7-6.4). Higher HbA1c values
      were associated with younger age, female gender, greater BMI, more comorbid
      diseases, lower EF, more 3-vessel coronary disease and recent MI (p trend for all
      <0.05). After adjustment for patient risk, greater HbA1c values were not
      associated with higher rates of in-hospital mortality or morbidity. Long-term
      survival was significantly worse as HbA1c increased. Risk of death increased by
      13% for every unit increase in HbA1c (adjHR=1.13, CI05% 1.07-1.19, P<.001).
      CONCLUSIONS: Pre-admission glycemic control, as assessed by HbA1c, is predictive
      of long-term survival with higher levels associated with poorer prognosis. It
      remains to be determined if this risk can be modified by better glycemic control
      post-operatively.

PMID- 30273571
TI  - The Prognostic Significance of c-MYC Amplification in Esophageal Squamous Cell
      Carcinoma.
AB  - BACKGROUND: We investigated the frequency of c-MYC amplification in esophageal
      squamous cell carcinoma (ESCC), including both stage I-II and III-IVa disease,
      and evaluated the correlation of c-MYC amplification with clinicopathologic
      parameters and outcome. METHODS: In 259 ESCC resected at Zhongshan Hospital,
      Fudan University from January 2007 to November 2010, c-MYC amplification was
      analyzed using tissue microarray, with fluorescence in situ hybridization (FISH)
      assay. RESULTS: c-MYC gene amplification was found in 43.2% (112/259) of ESCC
      patients. There were significant differences between c-MYC amplification and
      patient age (P=0.009), and lymph node metastasis (P=0.046). The median follow-up
      period was 33 months (range 4-102 months). There was a survival difference
      between patients with different c-MYC status. Among 112 patients with c-MYC
      amplification, a significantly poorer prognosis was observed, with a median DFS
      and OS of 24.0 and 31.0 months compared to 48.0 and 48.0 months for those without
      c-MYC amplification (P=0.011 and 0.018). Upon univariate and multivariate
      analysis, site, clinical stage, lymph node metastasis, adjuvant therapy and c-MYC
      amplification were associated with DFS and OS. When patients were divided into
      stage I-II and stage III-IV subgroups, c-MYC amplification tended to associate
      with poorer survival, but without statistical difference (P>0.05). CONCLUSIONS: c
      MYC amplification was associated with age and lymph node metastasis, and was an
      independent poor-prognostic factor for DFS and OS in full cohort of ESCC
      patients.

PMID- 30273573
TI  - Valve Sparing Root Replacement Provides Similar Mid-term Outcomes in Bicuspid and
      Trileaflet Valves (Commentary).

PMID- 30273574
TI  - Defining Proficiency for The Society of Thoracic Surgeons Participants Performing
      Thoracoscopic Lobectomy.
AB  - BACKGROUND: Parameters defining attainment and maintenance of proficiency in
      thoracoscopic video-assisted thoracic surgery (VATS) lobectomy remain unknown. To
      address this knowledge gap, this study investigated the institutional performance
      curve for VATS lobectomy by using risk-adjusted cumulative sum (Cusum) analysis.
      METHODS: Using The Society of Thoracic Surgeons General Thoracic Surgery
      Database, the study investigators identified centers that had performed a total
      of 30 or more VATS lobectomies. Major morbidity, mortality, and blood transfusion
      were deemed primary outcomes, with expected incidence derived from risk-adjusted
      regression models. Acceptable and unacceptable failure rates for outcomes were
      set a priori according to clinical relevance and informed by regression model
      output. RESULTS: Between 2001 and 2016, 24,196 patients underwent VATS lobectomy
      at 159 centers with a median volume of 103 (range, 30 to 760). Overall rates of
      operative mortality, major morbidity, and transfusion were 1% (244 of 24,189),
      17.1% (4,145 of 24,196), and 4% (975 of 24,196), respectively. Of the highest
      volume centers (>=100 cases), 84% (65 of 77) and 82 % (63 of 77) (p = 0.48) were
      proficient by major morbidity standards by their 50th and 100th cases,
      respectively. Similarly, 92% (71 of 77) and 90% (69 of 77) (p = 0.41) of centers
      showed proficiency by transfusion standards by their 50th and 100th cases,
      respectively. Three performance patterns were observed: (1) initial and sustained
      proficiency, (2) crossing unacceptability thresholds with subsequent improved
      performance; and (3) crossing unacceptability thresholds without subsequent
      improved performance. CONCLUSIONS: VATS lobectomy outcomes have improved with
      lower mortality and transfusion rates. The majority of high-volume centers
      demonstrated proficiency after 50 cases; however, maintenance of proficiency is
      not ensured. Cusum provides a simple yet powerful tool that can trigger internal
      audits and performance improvement initiatives.

PMID- 30273575
TI  - Assessing the spread of foot and mouth disease in mainland China by dynamical
      switching model.
AB  - In mainland China, there are three prevalent serotypes of foot and mouth disease
      virus (FMDV) and they circulate in different susceptible animals, which respond
      to viral infection in various ways and present different prevalent features.
      Although powerful control measures are carried on regularly, the epidemic are
      still prevalent in livestock. Therefore it is essential to assess the disease
      trends of foot and mouth disease (FMD) in domestic animals in mainland China. The
      participation of contaminated environment in the transmission dynamics has been
      confirmed in laboratory research and it can alter the conditions for FMDV
      invasion and persistence. So environment transmission plays a key role in disease
      spreading process. In this paper, we establish a dynamical switching model with
      environment transmission to investigate the relevant internal force mechanism
      with respect to the threshold switching, effect of saturation of the quantity of
      FMDV in environment, and prevalent characteristics of the disease in mainland
      China. Through the dynamical analysis of the model, we understand that under
      different conditions, there may appear coexistence of one, two, three or even
      four steady states, and bistability might occur, showing that the development
      trend of epidemic not only depends on the model parameters, but also is
      associated with the initial condition. We further study the influence of key
      parameters on the dynamical behavior and classify the parameter space into
      several regions with different composition patterns. Applying the model to assess
      the development trend of FMD in livestock in mainland China, we find that under
      certain conditions, some of the serotypes persists and some may disappear, thus
      we can provide some suggestions for disease control of prevailing serotype.

PMID- 30273576
TI  - A thermodynamic framework for modelling membrane transporters.
AB  - Membrane transporters contribute to the regulation of the internal environment of
      cells by translocating substrates across cell membranes. Like all physical
      systems, the behaviour of membrane transporters is constrained by the laws of
      thermodynamics. However, many mathematical models of transporters, especially
      those incorporated into whole-cell models, are not thermodynamically consistent,
      leading to unrealistic behaviour. In this paper we use a physics-based modelling
      framework, in which the transfer of energy is explicitly accounted for, to
      develop thermodynamically consistent models of transporters. We then apply this
      methodology to model two specific transporters: the cardiac
      sarcoplasmic/endoplasmic Ca2+ ATPase (SERCA) and the cardiac Na+/K+ ATPase.

PMID- 30273577
TI  - Interaction of palmitate and LPS regulates cytokine expression and apoptosis
      through sphingolipids in human retinal microvascular endothelial cells.
AB  - Studies have implicated saturated fatty acid (SFA) and lipopolysaccharide (LPS)
      in diabetic retinopathy. Since type 2 diabetes is associated with increases in
      both SFA and LPS in circulation, we investigated how SFA interacts with LPS to
      regulate proinflammatory cytokine expression and apoptosis in human retinal
      microvascular endothelial cells (HRMVECs) and the underlying mechanisms. HRMVECs
      were challenged with palmitate, a major SFA, LPS or palmitate plus LPS and the
      expression of proinflammatory cytokines were quantified using real-time PCR and
      enzyme-linked immunosorbent assay. The interaction between palmitate and LPS on
      inflammatory signaling and sphingolipid metabolism was demonstrated by
      immunoblotting and lipidomic analysis, respectively. The effect of palmitate and
      LPS on apoptosis was also studied by terminal deoxynucleotidyl transferase dUTP
      nick end labeling (TUNEL) and histone-associated DNA fragment assays. Results
      showed that palmitate robustly stimulated the expression of proinflammatory
      cytokines including interleukin (IL)-6 and IL-1beta, and the combination of
      palmitate and LPS further upregulated the proinflammatory cytokines by
      cooperatively stimulating inflammatory signaling pathways. Results also showed
      that while palmitate stimulated ceramide (CER) production via CER de novo
      synthesis and sphingomyelin (SM) hydrolysis, addition of LPS further increased
      CER de novo synthesis, but not SM hydrolysis. The involvement of sphingolipids in
      the cooperative stimulation by palmitate and LPS on cytokine expression was
      indicated by the findings that the inhibitor of CER de novo synthesis or SM
      hydrolysis attenuated the stimulation of IL-6 expression by palmitate and LPS. In
      addition, our study showed that fatty acid receptors GPR40 and CD36 were involved
      in the IL-6 upregulation by palmitate and LPS. Furthermore, palmitate induced
      apoptosis via CER production, but addition of LPS did not further increase
      apoptosis. Taken together, this study showed that palmitate interacted with LPS
      to upregulate cytokine expression via free fatty acid receptor-mediated
      inflammatory signaling and sphingolipid metabolism in HRMVECs. In contrast, the
      interaction between palmitate and LPS did not further increase apoptosis.

PMID- 30273578
TI  - Knockdown of the thyroid hormone transporter MCT8 in chicken retinal precursor
      cells hampers early retinal development and results in a shift towards more
      UV/blue cones at the expense of green/red cones.
AB  - Thyroid hormones (THs) play a crucial role in coordinating brain development in
      vertebrates. They fine-tune processes like cell proliferation, migration, and
      differentiation mainly by regulating the transcriptional activity of many
      essential genes. Regulators of TH availability thereby define the cellular
      concentration of the bioactive 3,5,3'-triiodothyronine, which binds to nuclear TH
      receptors. One important regulator, the monocarboxylate transporter 8 (MCT8),
      facilitates cellular TH uptake and is known to be necessary for correct brain
      development, but data on its potential role during retinal development is
      lacking. The retinal cyto-architecture has been conserved throughout vertebrate
      evolution, and we used the chicken embryo to study the need for MCT8 during
      retinal development. Its external development allows easy manipulation, and MCT8
      is abundantly expressed in the retina from early stages onwards. We induced MCT8
      knockdown by electroporating a pRFP-MCT8-RNAi vector into the retinal precursor
      cells (RPCs) at embryonic day 4 (E4), and studied the consequences for early (E6)
      and late (E18) retinal development. The empty pRFP-RNAi vector was used as a
      control. RPC proliferation was reduced at E6. This resulted in cellular
      hypoplasia and a thinner retina at E18 where mainly photoreceptors and horizontal
      cells were lost, the two predominant cell types that are born around the stage of
      electroporation. At E6, differentiation into retinal ganglion cells and amacrine
      cells was delayed. However, since the proportion of a given cell type within the
      transfected cell population at E18 was similar in knockdown and controls, the
      partial loss of some cell types was most-likely due to reduced RPC proliferation
      and not impaired cell differentiation. Photoreceptors displayed delayed migration
      at first, but had successfully reached the outer nuclear layer at E18. However,
      they increasingly differentiated into short wavelength-sensitive cones at the
      expense of medium/long wavelength-sensitive cones, while the proportion of rods
      was unaltered. Improperly formed sublaminae in the inner plexiform layer
      additionally suggested defects in synaptogenesis. Altogether, our data echoes
      effects of hypothyroidism and the loss of some other regulators of TH
      availability in the developing zebrafish and rodent retina. Therefore, the
      expression of MCT8 in RPCs is crucial for adequate TH uptake during cell type
      specific events in retinal development.

PMID- 30273579
TI  - Clustering of spin-labeled cholesterol analog diluted in bilayers of saturated
      and unsaturated phospholipids.
AB  - Clustering of spin-labeled cholesterol analog, 3beta-doxyl-5alpha-cholestane
      (DChl), diluted in bilayers comprised of either saturated dipalmitoyl-glycero
      phosphocholine (DPPC) or unsaturated dioleoyl-glycero-phosphocholine (DOPC)
      phospholipids was studied. DChl molar fraction X varied between 0.005 and 0.04.
      EPR spectroscopy applied at low temperatures (200 K) enabled exploring magnetic
      dipole-dipole (d-d) interaction between spin labels. For DOPC bilayers, EPR
      spectra were found to broaden remarkably with X increase. The broadening was
      simulated for the models of 2-dimentional (2-D) clusters with enhanced local
      concentration, Xloc, which was several times larger than X, and for 1-dimensional
      (1-D) DChl clusters. The distance of closest approach in these simulations
      attained the intermolecular lateral distance in the membrane (~0.7 nm). For DPPC
      bilayers, EPR spectra showed only small broadening, which in these simulations
      could not be reproduced even if Xloc was taken as small as X. However strong
      concentration dependence was found for electron spin echo (ESE) decays. Both the
      EPR and ESE data for DPPC bilayers were explained within the model assuming
      encapsulation of DChl molecules in lipid shells so preventing them to approach
      each other closer than a certain distance, Rmin. The Rmin value was found to vary
      between ~2.5 nm and 5 nm, for X varying between 0.04 and 0.005; Xloc in these
      simulations was several times larger than X. So the DChl clustering in DOPC
      bilayers is driven by attractive lipid-mediated forces, while in DPPC bilayers
      long-range nanoscale lipid-mediated repulsive/attractive forces take place for
      distances smaller and larger Rmin, correspondingly.

PMID- 30273580
TI  - Single-cell unroofing: probing topology and nanomechanics of native membranes.
AB  - Cell membranes separate the cell interior from the external environment. They are
      constituted by a variety of lipids; their composition determines the dynamics of
      membrane proteins and affects the ability of the cells to adapt. Even though the
      study of model membranes allows to understand the interactions among lipids and
      the overall mechanics, little is known about these properties in native
      membranes. To combine topology and nanomechanics analysis of native membranes, I
      designed a method to investigate the plasma membranes isolated from a variety of
      single cells. Five cell types were chosen and tested, revealing 20% variation in
      membrane thickness. I probed the resistance of the isolated membranes to indent,
      finding their line tension and spreading pressure. These results show that
      membranes isolated from neurons are stiffer and less diffusive than brain cancer
      cell membranes. This method gives direct quantitative insights on the mechanics
      of native cell membranes.

PMID- 30273581
TI  - Casein interaction with lipid membranes: Are the phase state or charge density of
      the phospholipids affecting protein adsorption?
AB  - Casein micelles are ~200 nm electronegative particles that constitute 80 wt% of
      the milk proteins. During synthesis in the lactating mammary cells, caseins are
      thought to interact in the form of ~20 nm assemblies, directly with the
      biological membranes of the endoplasmic reticulum and/or the Golgi apparatus.
      However, conditions that drive this interaction are not yet known. Atomic force
      microscopy imaging and force spectroscopy were used to directly observe the
      adsorption of casein particles on supported phospholipid bilayers with controlled
      compositions to vary their phase state and surface charge density, as verified by
      X-ray diffraction and zetametry. At pH 6.7, the casein particles adsorbed onto
      bilayer phases with zwitterionic and liquid-disordered phospholipid molecules,
      but not on phases with anionic or ordered phospholipids. Furthermore, the
      presence of adsorbed caseins altered the stability of the yet exposed bilayer.
      Considering their respective compositions and symmetry/asymmetry, these results
      cast light on the possible interactions of casein assemblies with the organelles'
      membranes of the lactating mammary cells.

PMID- 30273582
TI  - Maternal biomarkers for fetal heart failure in fetuses with congenital heart
      defects or arrhythmias.
AB  - BACKGROUND: Diagnosis of fetal heart failure depends primarily on fetal
      ultrasonography assessment. Our recent study demonstrated that plasma natriuretic
      peptide levels in umbilical cord blood were correlated with the severity of heart
      failure in fetuses with congenital heart defects or arrhythmias. However,
      percutaneous umbilical blood sampling is an invasive procedure, and therefore,
      less or noninvasive biomarkers reflecting fetal heart failure are required.
      OBJECTIVE: The aim of this study was to investigate the possibility of whether
      maternal serum biomarkers can diagnose fetal heart failure in fetuses with
      congenital heart defects or arrhythmias. STUDY DESIGN: This exploratory cross
      sectional study was conducted at a tertiary pediatric cardiac center. A total of
      50 singletons with fetal congenital heart defects or arrhythmias and 50 controls
      who were registered in the National Cerebral and Cardiovascular Center Biobank
      from 2013 to 2016 were included. Maternal serum samples obtained during the third
      trimester were analyzed for 2 hormones and 36 cytokines using the Bio-Plex Pro
      Human Cancer Biomarker panels 1 and 2. We comprehensively analyzed the
      association between maternal serum biomarkers and ultrasonography findings or
      fetal arrhythmia status. Fetal heart failure was defined as a cardiovascular
      profile score <=7. RESULTS: Of 37 fetuses with congenital heart defects, heart
      failure was found in 1 case of tricuspid valve dysplasia with moderate tricuspid
      regurgitation. Of 13 fetuses with arrhythmias, 5 had heart failure at 28-33 weeks
      of gestation. Maternal serum cytokine and hormone concentrations were compared
      between patients with and without fetal heart failure at 28-33 weeks of gestation
      (n = 6 and n = 61, respectively). Sixty-one fetuses without heart failure
      consisted of 10 with congenital heart defect, 6 with arrhythmia, and 45 controls.
      Maternal serum concentrations of tumor necrosis factor-alpha, interleukin-6,
      soluble Fas ligand, transforming growth factor-alpha, and vascular endothelial
      growth factor-D were significantly higher when fetuses had heart failure than
      when they did not (P < .05), whereas maternal serum concentrations of heparin
      binding epidermal growth factor-like growth factor were significantly lower when
      fetuses had heart failure than when they did not (P < .05). Multivariate analysis
      showed that maternal serum concentrations of tumor necrosis factor-alpha,
      vascular endothelial growth factor-D, and heparin-binding epidermal growth factor
      like growth factor were independently associated with fetal heart failure. The
      cutoff values were as follows: tumor necrosis factor-alpha, 68 pg/mL (sensitivity
      of 50.0%, specificity of 93.4%, positive likelihood ratio of 7.6, negative
      likelihood ratio of 0.5); vascular endothelial growth factor-D, 1156 pg/mL
      (sensitivity of 50.0%, specificity of 93.4%, positive likelihood ratio of 7.6,
      negative likelihood ratio of 0.5); and heparin-binding epidermal growth factor
      like growth factor, 90 pg/mL (sensitivity of 83.3%, specificity of 83.6%,
      positive likelihood ratio of 5.1, negative likelihood ratio of 0.2). The
      combination of these 3 cytokines showed sensitivity of 100%, specificity of
      80.3%, positive likelihood ratio of 5.1, and negative likelihood ratio of 0. In
      the absence of fetal heart failure, concentrations of all maternal serum
      cytokines and hormones were similar in cases of fetal congenital heart defects
      and controls, while maternal serum soluble CD40 ligand concentrations were
      increased only in fetal arrhythmias. CONCLUSION: Maternal serum concentrations of
      tumor necrosis factor-alpha, vascular endothelial growth factor-D, and heparin
      binding epidermal growth factor-like growth factor were associated with fetal
      heart failure.

PMID- 30273583
TI  - Interpersonal trauma and aging-related genitourinary dysfunction in a national
      sample of older women.
AB  - BACKGROUND: Among reproductive-aged women, exposure to interpersonal trauma is
      associated with genitourinary symptoms. Little is known about the relationship
      between these exposures and the genitourinary health of older women, who tend to
      experience different and more prevalent genitourinary symptoms because of
      menopause and aging. OBJECTIVES: In this study, we examined relationships between
      common types of interpersonal trauma and aging-related genitourinary dysfunction
      among older women. STUDY DESIGN: We analyzed data from the National Social Life,
      Health, and Aging Project, a national area probability sample of older community
      dwelling adults born between 1920 and 1947. We used cross-sectional data from
      home-based study visits conducted in 2005-2006 to examine interpersonal violence
      exposures (any lifetime sexual assault, past-year emotional and physical abuse),
      and past-year genitourinary symptoms (urinary incontinence, other urinary
      problems, and vaginal pain/lubrication problems with sexual intercourse) among
      women participants. Multivariable logistic regression models were used to relate
      interpersonal violence and genitourinary symptoms, adjusting for age,
      race/ethnicity, body mass index, education, marital status, parity, hormone
      therapy, depressive and anxiety symptoms, and self-reported health. In
      exploratory models, we further adjusted for vaginal maturation, a tissue-specific
      marker of aging-related urogenital atrophy obtained from vaginal self-swabs.
      RESULTS: In this national sample of 1551 older women (mean age 69 +/- 2 years),
      9% reported sexual assault, 23% reported emotional abuse, and <1% reported
      physical abuse. Urinary incontinence and other urinary problems were reported by
      42% and 17%, respectively, and 42% of sexually active women (n = 527) reported
      vaginal symptoms with intercourse. In multivariable regression analyses adjusted
      for age, race/ethnicity, education, marital status, parity, hormone therapy,
      anxiety, depressive symptoms, and self-reported health, women with any lifetime
      history of sexual assault had 2.5 times the odds (95% confidence interval, 1.0
      6.3) of vaginal symptoms, while women who reported past-year emotional abuse had
      higher odds of urinary incontinence (odds ratio, 1.7, 95% confidence interval,
      1.2-2.4) and other urinary problems (odds ratio, 1.8, 95% confidence interval,
      1.2-2.8). Among women who provided vaginal self-swabs (n = 869), adjustment for
      vaginal maturation-attenuated associations with other urinary problems (odds
      ratio, 1.6, 95% confidence interval, .9-2.6) and vaginal symptoms (odds ratio,
      2.2, 95% confidence interval, 0.8-5.8). CONCLUSION: Sexual assault and emotional
      abuse may play a role in the development or experience of aging-related
      genitourinary dysfunction in older women. Clinicians caring for older women
      should recognize the prevalence and importance of traumatic exposures in health
      related to menopause and aging.

PMID- 30273584
TI  - Tackling poorly selected, collected, and reported outcomes in obstetrics and
      gynecology research.
AB  - Clinical research should ultimately improve patient care. To enable this,
      randomized controlled trials must select, collect, and report outcomes that are
      both relevant to clinical practice and genuinely reflect the perspectives of key
      stakeholders including health care professionals, researchers, and patients.
      Unfortunately, many randomized controlled trials fall short of this requirement.
      Complex issues, including a failure to take into account the perspectives of key
      stakeholders when selecting outcomes, variations in outcome definitions and
      measurement instruments, and outcome reporting bias make research evidence
      difficult to interpret, undermining the translation of research into clinical
      practice. Problems with poor outcome selection, measurement, and reporting can be
      addressed by developing, disseminating, and implementing core outcome sets. A
      core outcome set represents a minimum data set of outcomes developed using robust
      consensus science methods engaging diverse stakeholders including health care
      professionals, researchers, and patients. Core outcomes should be routinely
      utilized by researchers, collected in a standardized manner, and reported
      consistently in the final publication. They are currently being developed across
      our specialty including infertility, endometriosis, and preeclampsia. Recognizing
      poorly selected, collected, and reported outcomes as serious hindrances to
      progress in our specialty, more than 80 journals including the Journal, have come
      together to support the Core Outcomes in Women's and Newborn Health (CROWN)
      initiative. The consortium supports researchers to develop, disseminate, and
      implement core outcome sets. Implementing core outcome sets could make a profound
      contribution to addressing poorly selected, collected, and reported outcomes.
      Implementation should ensure future randomized controlled trials hold the
      necessary reach and relevance to inform clinical practice, enhance patient care,
      and improve patient outcomes.

PMID- 30273585
TI  - Early preterm preeclampsia outcomes by intended mode of delivery.
AB  - BACKGROUND: The optimal route of delivery in early-onset preeclampsia before 34
      weeks is debated because many clinicians are reluctant to proceed with induction
      for perceived high risk of failure. OBJECTIVE: Our objective was to investigate
      labor induction success rates and compare maternal and neonatal outcomes by
      intended mode of delivery in women with early preterm preeclampsia. STUDY DESIGN:
      We identified 914 singleton pregnancies with preeclampsia in the Consortium on
      Safe Labor study for analysis who delivered between 24 0/7 and 33 6/7 weeks. We
      excluded fetal anomalies, antepartum stillbirth, or spontaneous preterm labor.
      Maternal and neonatal outcomes were compared between women undergoing induction
      of labor (n = 460) and planned cesarean delivery (n = 454) and women with
      successful induction of labor (n = 214) and unsuccessful induction of labor (n =
      246). We calculated relative risks and 95% confidence intervals to determine
      outcomes by Poisson regression model with propensity score adjustment. The
      calculation of propensity scores considered covariates such as maternal age,
      gestational age, parity, body mass index, tobacco use, diabetes mellitus, chronic
      hypertension, hospital type and site, birthweight, history of cesarean delivery,
      malpresentation/breech, simplified Bishop score, insurance, marital status, and
      steroid use. RESULTS: Among the 460 women with induction (50%), 47% of deliveries
      were vaginal. By gestational age, 24 to 27 6/7, 28 to 31 6/7, and 32 to 33 6/7,
      the induction of labor success rates were 38% (12 of 32), 39% (70 of 180), and
      54% (132 of 248), respectively. Induction of labor compared with planned cesarean
      delivery was less likely to be associated with placental abruption (adjusted
      relative risk, 0.33; 95% confidence interval, 0.16-0.67), wound infection or
      separation (adjusted relative risk, 0.23; 95% confidence interval, 0.06-0.85),
      and neonatal asphyxia (0.12; 95% confidence interval, 0.02-0.78). Women with
      vaginal delivery compared with those with failed induction of labor had decreased
      maternal morbidity (adjusted relative risk, 0.27; 95% confidence interval, 0.09
      0.82) and no difference in neonatal outcomes. CONCLUSION: About half of women
      with preterm preeclampsia who attempted an induction had a successful vaginal
      delivery. The rate of successful vaginal delivery increases with gestational age.
      Successful induction has the benefit of preventing maternal and fetal
      comorbidities associated with previous cesarean deliveries in subsequent
      pregnancies. While overall rates of a composite of serious maternal and neonatal
      morbidity/mortality did not differ between induction of labor and planned
      cesarean delivery groups, women with failed induction of labor had increased
      maternal morbidity highlighting the complex route of delivery counseling required
      in this high-risk population of women.

PMID- 30273586
TI  - Liposomal bupivacaine efficacy for postoperative pain following posterior vaginal
      surgery: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Effective postoperative pain management is a crucial component of
      recovery following surgery. Narcotics are a cornerstone of postoperative
      analgesia, but can require a redosing requirement, encompass a lengthy list of
      side effects and adverse reaction risks, as well as carry a dependency potential.
      The national focus on decreasing opioid use has directly impacted postoperative
      pain management. Previous studies have reported the beneficial use of a single
      intraoperative injection of extended-release liposomal bupivacaine in
      postoperative pain management, however the same results have not been extensively
      studied in the urogynecology literature. OBJECTIVE: We sought to evaluate
      cumulative postoperative vaginal pain on days 1 and 3 after posterior vaginal
      wall surgery comparing study medication (extended-release liposomal bupivacaine)
      to placebo (saline). Secondary aims were to evaluate vaginal pain on
      postoperative day 7 and total morphine-equivalent narcotic usage on days 1, 3,
      and 7. STUDY DESIGN: This is a randomized, double-blinded, placebo-controlled
      trial with 100 subjects recruited from Walter Reed National Military Medical
      Center urogynecology clinic. All subjects were age >18 years and scheduled for
      surgery involving the posterior vaginal wall or muscularis (including posterior
      colporrhaphy, colpocleisis, sphincteroplasty, perineorrhaphy), excluding those
      with regular narcotic usage or concurrent pain management requiring the use of
      epidural anesthesia. A sample size of 96 patients was calculated. Subjects were
      randomized to receive either 20 mL of extended-release liposomal bupivacaine
      (Exparel) (Pacira Pharmaceuticals Inc, Parsippany, NJ) or 20 mL of placebo
      (saline) at the end of surgery. Concealed syringes were used and injected
      immediately postoperative into the lateral vaginal wall/levator muscle area and
      perineal body. In-house morphine-equivalent narcotic usage was recorded along
      with the postoperative day 1 pain scores. Patients were contacted by telephone on
      postoperative days 3 and 7. Vaginal pain scores were evaluated using the Defense
      and Veterans Pain Rating Scale, cumulatively and on days 1, 3, and 7. Overall
      morphine-equivalent narcotics were compared between the 2 groups. RESULTS: From
      October 2014 through August 2017, 100 patients were enrolled and completed the
      study; 49 (49%) of the patients were randomized to the study group and 51 (51%)
      were in the placebo group. There was no significant difference between vaginal
      pain scores between the study group and the placebo group (postoperative day 1:
      study medication median score 1 [interquartile range 0-3], placebo median score 1
      [interquartile range 0-3] [P = .59]; postoperative day 3: study medication median
      score 2 [interquartile range 0-3], placebo median score 1 [interquartile range 0
      3] [P = .20]; postoperative day 7: study medication median score 3 [interquartile
      range 1-4], placebo median score 1.5 [interquartile range 0-3] [P = .06]).
      Cumulative pain scores postoperative day 1-7 were also not significant (study
      medication median score 6 [interquartile range 1-10], placebo median score 4
      [interquartile range 1-8] [P = .14]). Multivariate model for the presence of
      vaginal pain was calculated and after controlling for body mass index, age, and
      combined laparoscopy surgery, there was no significant difference between the
      study and the placebo groups (P = .62). There was no statistically significant
      difference in morphine equivalents for the 2 groups: study medication 112.5
      (interquartile range 45-207) and placebo 101.5 (interquartile range 37.5-195), P
      = .81. CONCLUSION: The use of extended-release liposomal bupivacaine in posterior
      vaginal wall surgeries, injected into the lateral posterior vaginal wall and
      perineal body, does not provide a significant decrease in postoperative pain or
      decrease narcotic medication usage when compared to saline.

PMID- 30273587
TI  - Trends in pregnancy-associated mortality involving opioids in the United States,
      2007-2016.

PMID- 30273588
TI  - Association of levator injury and urogynecological complaints in women after
      their first vaginal birth with and without mediolateral episiotomy.
AB  - BACKGROUND: Pelvic organ prolapse is a common health problem in women and has a
      negative influence on quality of life. A major cause of pelvic organ prolapse is
      levator injury. OBJECTIVE: The objective of the study was to evaluate the
      association of mediolateral episiotomy with levator injury (levator avulsion,
      ballooning, or combined) and urogynecological complaints. STUDY DESIGN: A
      prospective observational cohort study was performed in 204 primiparous women
      with a spontaneous vaginal delivery without anal sphincter tear in a general
      hospital between 2012 and 2015. One hundred three of these women had had a
      mediolateral episiotomy. Validated urogynecological questionnaires and
      transperineal 3-dimensional/4-dimensional ultrasound were completed after
      delivery. Outcome measures were levator avulsion, ballooning (hiatal area of more
      than 25 cm2), and urogynecological questionnaire scores. Statistical analysis was
      performed using univariate and multiple logistic regression analysis. RESULTS:
      The median time at investigation after vaginal delivery was 13 months (range 6
      33). Levator injury (avulsion, ballooning, or combined) was identified in 35 of
      the 103 women who had undergone mediolateral episiotomy (40.0%) and 33 of the 101
      women without episiotomy (32.7%) (P = .69). No differences were found in the
      incidence of levator avulsion 27 (26.7%) vs 23 (22.8%) (P = .53) or in levator
      ballooning (20 [19.4%] vs 23 [22.8%] (P = .58) between both groups. There was an
      association between longer duration of the second stage of labor and the
      incidence of levator avulsion (odds ratio, 1.24 [95% confidence interval, 1.01
      1.52]). Nonocciput anterior fetal position increased the risk of levator
      ballooning and levator injury (odds ratio, 10.19 [95% confidence interval, 1.89
      54.91] and odds ratio, 12.16 [95% confidence interval, 1.41-104.38],
      respectively). No differences in urogynecological complaints were found.
      CONCLUSION: Mediolateral episiotomy is not associated with the occurrence of
      levator injury or urogynecological complaints in women with a spontaneous vaginal
      delivery who did not obtain an anal sphincter injury. Levator injury was
      associated with a prolonged second stage of labor and a nonocciput anterior fetal
      position.

PMID- 30273589
TI  - Quality of life and fear of cancer recurrence in T1 colorectal cancer patients
      treated with endoscopic or surgical tumor resection.
AB  - BACKGROUND AND AIMS: To optimize therapeutic decision-making in T1 colorectal
      cancer (T1 CRC) patients, it is important to elicit the patient's perspective
      next to considering medical outcome. Because empirical data on patient-reported
      impact of different treatment options are lacking, we evaluated patients' quality
      of life, perceived time to recovery and fear of cancer recurrence after
      endoscopic or surgical treatment for T1 CRC. METHODS: In this cross-sectional
      study, we selected patients with histologically confirmed T1 CRC, who
      participated in the Dutch Bowel Cancer Screening Programme and received
      endoscopic or surgical treatment between January 2014 and July 2017. Quality of
      life was measured using the EORTC QLQ-C30 and the EQ-5D-5L questionnaire. We used
      the Cancer Worry Scale (CWS) to evaluate patients' fear of cancer recurrence. A
      question on perceived time to recovery after treatment was also included in the
      set of questionnaires sent to the patients. RESULTS: Of all 119 eligible
      patients, 92.4% responded to the questionnaire (endoscopy group: 55/62, surgery
      group: 55/57). Compared with the surgery group, perceived time to recovery was on
      average 3 months shorter in endoscopically treated patients after adjustment for
      confounders (19.9 days vs 111.3 days; p = 0.001). The 2 treatment groups were
      comparable with regard to global quality of life, functioning domains as well as
      symptom severity scores. Moreover, patients in the endoscopy group did not report
      more fear of cancer recurrence than those in the surgery group (CWS score range 0
      40; endoscopy: 7.6 vs surgery: 9.7; p = 0.140). CONCLUSIONS: From the patient's
      perspective, endoscopic treatment provides a quicker recovery than surgery,
      without provoking more fear of cancer recurrence or any deterioration in quality
      of life. These results contribute to the shared therapeutic decision-making
      process of clinicians and T1 CRC patients.

PMID- 30273590
TI  - Blue-light imaging compared with high-definition white light for real-time
      histology prediction of colorectal polyps less than 1 centimeter: a prospective
      randomized study.
AB  - BACKGROUND AND AIMS: Blue-light imaging (BLI) is a new chromoendoscopy technique,
      potentially useful for differentiating neoplastic from nonneoplastic lesions. The
      present study was aimed at comparing BLI with high-definition white light (HDWL)
      in the real-time histology prediction of colon polyps <10 mm. METHODS:
      Consecutive outpatients undergoing colonoscopy with the ELUXEO 7000 endoscopy
      platform and 760 series video colonoscopes (Fujifilm Co, Tokyo, Japan) who had at
      least 1 polyp <10 mm were randomized to BLI or HDWL for polyp characterization.
      The accuracy of high-confidence real-time histology prediction (adenoma vs not
      adenoma) by either BLI or HDWL for polyps <10 mm (primary end-point) and
      diminutive (<=5 mm) polyps was calculated, along with sensitivity, specificity,
      and positive and negative predictive values, with histopathology as the reference
      standard. RESULTS: A total of 483 polyps were detected in 245 randomized patients
      (125 and 120 in the BLI and HDWL arms, respectively). A total of 358 were
      diminutive, and 283 were adenomas. Overall, 222 (85.7%) and 193 (86.1%) polyps
      were characterized with high confidence by BLI and HDWL, respectively (P = .887),
      with an overall accuracy of 92% and 84%, respectively (P = .011). The accuracy
      was significantly higher by BLI than HDWL, also for diminutive polyps (92% vs
      83%; P = .008). When BLI was used, the negative predictive value for diminutive
      rectosigmoid polyps was 88%, and the post-polypectomy surveillance interval was
      correctly attributed in 85.7% and 93.7% of patients, respectively, according to
      U.S. and European guidelines. CONCLUSION: BLI was superior to HDWL for the real
      time prediction of histology in polyps <10 mm. A BLI-dedicated classification
      might further improve the endoscopist performance. (Clinical trial registration
      number: NCT03274115.).

PMID- 30273592
TI  - Clinical disease activity and endoscopic severity correlate poorly in children
      newly diagnosed with Crohn's disease.
AB  - BACKGROUND AND AIMS: Treatment goals in Crohn's disease (CD) have evolved to
      target mucosal healing. There is now a drive to determine if noninvasive measures
      can adequately identify the attainment and persistence of this goal. Currently,
      data describing the relationship between clinical indices and endoscopic
      appearance in pediatric CD are sparse. Our aim was to compare endoscopic severity
      with the weighted Pediatric Crohn's Disease Activity Index (wPCDAI) in children
      with newly diagnosed CD. METHODS: All children aged <=17 years newly diagnosed
      with CD enrolled in an inception cohort at sites of the Canadian Children
      Inflammatory Bowel Disease Network were eligible. Clinical disease activity at
      presentation was evaluated by the wPCDAI and conventional biochemical parameters.
      Severity of disease at ileocolonoscopy was assessed by the simple endoscopic
      score for CD (SES-CD), with segmental subscores noted. We evaluated the
      association of SES-CD and disease activity markers using the Pearson test of
      correlation, the Spearman rank coefficient, and linear regression models.
      RESULTS: Two hundred eighty patients from 11 centers were included in the
      analysis. The median wPCDAI score was 60 (interquartile range, 40-80; 53%
      severe). Median SES-CD was 16 (interquartile range 10-22; 51% severe). The wPCDAI
      correlated weakly with SES-CD (r = .39, P < .001). Examination of the individual
      components that contribute to the wPCDAI demonstrated weak correlation with the
      SES-CD for all items apart from stooling (moderate correlation, r = .50, P <
      .001). Routine blood tests did not correlate well with the SES-CD. In regression
      models, variation in clinical symptoms accounted for most of the variation in
      both the wPCDAI and SES-CD, with no additional benefit from routine blood tests.
      CONCLUSIONS: In children with newly diagnosed CD, wPCDAI correlates poorly with
      endoscopic disease activity. As treatment paradigms evolve to target mucosal
      healing, clinical markers should not be used in isolation to determine disease
      activity.

PMID- 30273593
TI  - Repeated Cannabidiol treatment reduces cocaine intake and modulates neural
      proliferation and CB1R expression in the mouse hippocampus.
AB  - Cannabinoid derivatives have shown promising results for treating
      neuropsychiatric disorders, including drug addiction. Recent studies on the
      therapeutic effects of Cannabidiol (CBD) on drug abuse showed mixed results,
      especially with psychostimulant substances such as cocaine. To determine whether
      CBD can attenuate cocaine reinforcement, we assessed behavioural responses
      induced by cocaine in mice, using the behavioural sensitization, conditioned
      place preference and intravenous self-administration paradigms. We show that
      repeated CBD treatment produces anxiolytic effects in the elevated plus maze
      test, increases the discrimination index of the novel object recognition task and
      attenuates cocaine-induced conditioned place preference but does not affect
      behavioural sensitization. CBD reduced cocaine voluntary consumption and
      progressive ratio breaking point in the self-administration paradigm, but not
      drug-induced reinstatement. In parallel, CBD increased expression of type 1
      cannabinoid receptor, MAPK-CREB phosphorylation, BDNF expression, and neural cell
      proliferation in the hippocampus, and reduced the GluA1/2 AMPA subunit receptor
      ratio in the striatum. In summary, we show that CBD can modulate some behavioural
      and molecular manifestations of cocaine reinforcement. Moreover, our findings
      show that CBD has pro-neurogenic effects also in cocaine consuming animals.
      Overall, this novel evidence provides new perspectives to use CBD as a
      therapeutic tool.

PMID- 30273591
TI  - G-EYE colonoscopy is superior to standard colonoscopy for increasing adenoma
      detection rate: an international randomized controlled trial (with videos).
AB  - BACKGROUND AND AIMS: Colorectal cancer (CRC) is largely preventable with routine
      screening and surveillance colonoscopy; however, interval cancers arising from
      precancerous lesions missed by standard colonoscopy still occur. An increased
      adenoma detection rate (ADR) has been found to be inversely associated with
      interval cancers. The G-EYE device includes a reusable balloon integrated at the
      distal tip of a standard colonoscope, which flattens haustral folds, centralizes
      the colonoscope's optics, and reduces bowel slippage. The insufflated balloon
      also aims to enhance visualization of the colon during withdrawal, thereby
      increasing the ADR. METHODS: In this randomized, controlled, international,
      multicenter study (11 centers), patients (aged >=50 years) referred to
      colonoscopy for screening, surveillance, or changes in bowel habits were
      randomized to undergo either balloon-assisted colonoscopy by using an insufflated
      balloon during withdrawal or standard high-definition colonoscopy. The primary
      endpoint was the ADR. RESULTS: One thousand patients were enrolled between May
      2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803
      were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy
      n = 407). Baseline parameters were similar in both groups. Balloon-assisted
      colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy
      group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy
      provided for a significant increase in detection of advanced (P = .0033) flat
      adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026).
      CONCLUSION: Balloon-assisted colonoscopy yielded a higher ADR and increased the
      detection of advanced, flat, and sessile serrated adenomas/polyps when compared
      with standard colonoscopy. Improved detection by the G-EYE device could impact
      the quality of CRC screening by reducing miss rates and consequently reducing
      interval cancer incidence. (Clinical trial registration number: NCT01917513.).

PMID- 30273594
TI  - Varenicline reduces DNA damage, tau mislocalization and post surgical cognitive
      impairment in aged mice.
AB  - Postoperative cognitive dysfunction (POCD) occurs more frequently in elderly
      patients undergoing major surgery. Age associated cholinergic imbalance may
      exacerbate postoperative systemic and neuroinflammation, but the effect nicotinic
      acetylcholine receptor (nAchR) stimulation on the development of POCD remains
      unclear. Aged male C57BL/6N mice (18 months old) underwent a midline laparotomy
      or were exposed to sevoflurane anesthesia alone (4-5%), with or without
      concomitant varenicline, a partial nAchR, at 1 mg/kg/day. Laparotomy increased
      pro-inflammatory cytokines in the liver and hippocampus (IL-1beta and MCP-1) and
      induced a decline in cognitive performance, indicated by lower discrimination
      index in the Novel Object Recognition test, greater error number and longer
      escape latency in the Y-maze test. Glia activation, aberrant tau phosphorylation
      (AT8) and accumulation of phosphorylated H2AX in the hippocampus were detectable
      up to postoperative day 14, with neuronal apoptosis seen in the hippocampus.
      Perioperative varenicline attenuated the cognitive decline and associated tau
      protein mislocalization, DNA damage and neuronal apoptosis. The modulation of
      JAK2/STAT3 signaling may play a critical role in this process. Neuroinflammation,
      tau phosphorylation and DNA damage contribute to the development of cognitive
      dysfunction following laparotomy. Cholinergic stimulation by varenicline
      attenuated these changes through preventing the mislocalization of phosphorylated
      tau and DNA damage.

PMID- 30273596
TI  - Notch-signaling activity determines uptake and biological effect of imatinib in
      systemic sclerosis dermal fibroblasts.
AB  - Tyrosine kinase inhibitors (TKI) have emerged as therapeutic option for rheumatic
      diseases such as systemic sclerosis (SSc). Since TKs like c-Abl kinase are
      important for fibroblast activation and fibrosis development in SSc, the c-Abl
      inhibitor imatinib was proposed for SSc treatment. Transporters for organic
      cations have become increasingly recognized as an important determinant for
      uptake and efficacy of TKI. Therefore, we investigated the role of organic cation
      transporters in the uptake of imatinib. Moreover, the influence of important SSc
      pathogenetic factors, like PDGF and Notch- pathway activation on these uptake
      processes, has been studied. We demonstrated that the organic cation transporters
      (OCT) 1-3, the OCTN novel (OCTN)1-2, and the multidrug and toxin extrusion
      protein MATE1 are expressed in healthy dermal and SSc fibroblasts. Interestingly,
      decreased expression levels of MATE1 and decreased imatinib uptake were measured
      in SSc fibroblasts. In siRNA experiments, MATE1 was identified as key transporter
      for imatinib uptake and biological effect in dermal fibroblasts. Furthermore,
      PDGF reduced imatinib uptake by decreasing MATE1 expression in SSc fibroblasts,
      but not in healthy fibroblasts. Blocking the Notch pathway in SSc fibroblasts
      increased MATE1 transporter expression and imatinib uptake. In conclusion, MATE1
      mediated transport governs therapeutic efficacy of imatinib in SSc.

PMID- 30273598
TI  - Protective Role of Autophagy in Nlrp3 Inflammasome Activation and Medial
      Thickening of Mouse Coronary Arteries.
AB  - We hypothesized that autophagy and associated lysosome function serve as a
      critical modulator during Nod-like receptor family pyrin domain containing 3
      (Nlrp3) inflammasome activation on proatherogenic stimuli. We first demonstrated
      that 7-ketocholesterol stimulated Nlrp3 inflammasome formation and activation as
      shown by increased colocalization of inflammasome components [Nlrp3 versus
      apoptosis associated speck-like protein (Asc) or caspase-1] and enhanced cleavage
      of caspase-1 into active caspase-1 to generate IL-1beta in coronary artery smooth
      muscle cells. Deletion of the CD38 gene (CD38-/-) that regulates lysosome
      function and autophagic flux also led to Nlrp3 inflammasome formation and
      activation. In the presence of rapamycin, the effects of either 7-ketocholesterol
      treatment or CD38 gene deletion were abolished. The autophagy inhibitor spautin-1
      and the lysosome function blocker bafilomycin A1 also enhanced Nlrp3 inflammasome
      formation and activation. In animal experiments, we found that increased
      colocalization of Nlrp3 versus Asc or caspase-1 enhanced IL-1beta accumulation
      and caspase-1 activity in the coronary arterial wall of CD38-/- mice on the
      Western diet compared with CD38+/+ mice. This increased colocalization was
      blocked by treatment with rapamycin but enhanced by chloroquine, a water-soluble
      blocker of autophagic flux. Morphologic examinations confirmed that the media of
      coronary arteries was significantly thicker in CD38-/- mice on the Western diet
      than CD38+/+ mice. In conclusion, the deficiency of autophagic flux promotes
      Nlrp3 inflammasome formation and activation in coronary artery smooth muscle
      cells on proatherogenic stimulation, leading to medial thickening of the coronary
      arterial wall.

PMID- 30273597
TI  - NEDD4 Is Involved in Inflammation Development during Keloid Formation.
AB  - Keloids mark a chronic inflammatory disease characterized by a fibroproliferative
      disorder of the skin. A genome-wide association study showed that single
      nucleotide polymorphism rs8032158 in the neural precursor cell-expressed NEDD4
      gene, which has six protein-coding transcript variants (TVs), is genetically
      linked to keloids. Here, we show that the high frequency of risk allele C in
      rs8032158 in keloid patients is associated with a selectively higher expression
      of TV3 of NEDD4 to activate the NF-kappaB pathway. Comparisons of keloid scars
      with normal skin samples that do not have the single-nucleotide polymorphism
      allele and were derived from different anatomical sites showed stronger
      expressions of NEDD4 TV3 and activated forms of NF-kappaB and STAT3 in keloid
      scars. Forced expression or selective knockdown of NEDD4 TV3 increased or
      decreased NF-kappaB activation in vitro. Furthermore, NEDD4 knockdown suppressed
      NF-kappaB-dependent inflammation development in vivo. Mechanistic analysis showed
      that NEDD4 TV3 is involved in NF-kappaB activation through its association with
      the adaptor protein RIP. These results suggest that NEDD4 TV3 is a potential
      diagnostic marker and therapeutic target for chronic skin diseases, including
      keloid.

PMID- 30273595
TI  - Hippocampal neural progenitor cells play a distinct role in fear memory retrieval
      in male and female CIE rats.
AB  - Adult male and female GFAP-TK transgenic rats experienced six weeks of chronic
      intermittent ethanol vapor inhalation (CIE). During the last week of CIE, a
      subset of male and female TK rats were fed with Valcyte to ablate neural
      progenitor cells (NPCs). Seventy-two hours after CIE cessation, all CIE and age
      matched ethanol naive controls experienced auditory trace fear conditioning
      (TFC). Twenty-four hours later all animals were tested for cue-mediated retrieval
      in the fear context. Adult male CIE rats showed a significant burst in NPCs
      paralleled by reduction in fear retrieval compared to naive controls and Valcyte
      treated CIE rats. Adult female CIE rats did not show a burst in NPCs and showed
      similar fear retrieval compared to naive controls and Valcyte treated CIE rats,
      indicating that CIE-mediated impairment in fear memory and its regulation by NPCs
      was sex dependent. Valcyte significantly reduced Ki-67 and NeuroD labeled cells
      in the dentate gyrus (DG) in both sexes, demonstrating a role for NPCs in reduced
      fear retrieval in males. Valcyte prevented adaptations in GluN2A receptor
      expression and synaptoporin density in the DG in males, indicating that NPCs
      contributed to alterations in plasticity-related proteins and mossy fiber
      projections that were associated with reduced fear retrieval. These data suggest
      that DG NPCs born during withdrawal and early abstinence from CIE are aberrant,
      and could play a role in weakening long-term memory consolidation dependent on
      the hippocampus.

PMID- 30273599
TI  - Enteroviral Infection Leads to Transactive Response DNA-Binding Protein 43
      Pathology in Vivo.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that
      primarily affects motor neurons in the cerebral cortex, brainstem, and spinal
      cord, leading to progressive paralysis and eventual death. Approximately 95% of
      all ALS cases are sporadic without known causes. Enteroviruses have been
      suspected to play a role in ALS because of their ability to target motor neurons
      and to cause muscle weakness and paralysis. In vitro enteroviral infection
      results in cytoplasmic aggregation and cleavage of transactive response DNA
      binding protein-43, a pathologic hallmark of ALS. However, whether enteroviral
      infection can induce ALS-like pathologies in vivo remains to be characterized. In
      this study, neonatal BALB/C mice were intracranially inoculated with either a
      recombinant coxsackievirus B3 expressing enhanced green fluorescent protein or
      mock-infected for 2, 5, 10, 30, and 90 days. Histologic and immunohistochemical
      analysis of brain tissues demonstrated sustained inflammation (microglia and
      astrogliosis) and lesions in multiple regions of the brain (hippocampus, cerebral
      cortex, striatum, olfactory bulb, and putamen) in parallel with virus detection
      as early as 2 days for up to 90 days after infection. Most notably, ALS-like
      pathologies, including cytoplasmic mislocalization of transactive response DNA
      binding protein-43, p62-, and ubiquitin-positive inclusions, were observed in the
      areas of infection. These data provide the first pathologic evidence to support a
      possible link between enteroviral infection and ALS.

PMID- 30273600
TI  - Colonoscopic-Guided Pinch Biopsies in Mice as a Useful Model for Evaluating the
      Roles of Host and Luminal Factors in Colonic Inflammation.
AB  - Colonic inflammation, a hallmark of inflammatory bowel disease, can be influenced
      by host intrinsic and extrinsic factors. There continues to be a need for models
      of colonic inflammation that can both provide insights into disease pathogenesis
      and be used to investigate potential therapies. Herein, we tested the utility of
      colonoscopic-guided pinch biopsies in mice for studying colonic inflammation and
      its treatment. Gene expression profiling of colonic wound beds after injury
      showed marked changes, including increased expression of genes important for the
      inflammatory response. Interestingly, many of these gene expression changes
      mimicked those alterations found in inflammatory bowel disease patients. Biopsy
      induced inflammation was associated with increases in neutrophils, macrophages,
      and natural killer cells. Injury also led to elevated levels of sphingosine-1
      phosphate (S1P), a bioactive lipid that is an important mediator of inflammation
      mainly through its receptor, S1P1. Genetic deletion of S1P1 in the endothelium
      did not alter the inflammatory response but led to increased colonic bleeding.
      Bacteria invaded into the wound beds, raising the possibility that microbes
      contributed to the observed changes in mucosal gene expression. In support of
      this, reducing bacterial abundance markedly attenuated the inflammatory response
      to wounding. Taken together, this study demonstrates the utility of the pinch
      biopsy model of colonic injury to elucidate the molecular underpinnings of
      colonic inflammation and its treatment.

PMID- 30273601
TI  - Intrauterine Programming of Glucocorticoid-Insulin-Like Growth Factor-1 Axis
      Mediated Developmental Origin of Osteoporosis Susceptibility in Female Offspring
      Rats with Prenatal Caffeine Exposure.
AB  - Epidemiologic investigations suggest that excessive intake of caffeine during
      pregnancy is one of the risk factors for osteoporosis in adult offspring.
      However, the phenomena and mechanisms have remained obscure. This study found
      that prenatal caffeine exposure (PCE) leads to persistent bone dysplasia in
      gestational day 20 and postnatal week 12 offspring rats and increases the
      susceptibility to osteoporosis in postnatal week 28 offspring rats. In the
      embryonic period, PCE increases the concentration of serum corticosterone and
      inhibits the expression of insulin-like growth factor-1 (IGF1) and osteogenic
      differentiation genes. After birth, the recovery of IGF1 expression in PCE
      offspring is unable to completely compensate osteogenic function, and chronic
      stress can lead to a further decrease in IGF1 expression. In vitro experiments
      found that corticosterone instead of caffeine restrains mineralized nodule
      formation and osteoblast differentiation by inhibiting IGF1 expression. The
      corticosterone inhibits H3K9 and H3K14 histone acetylation of IGF1 in osteoblasts
      through glucocorticoid receptor and CCAAT and enhancer binding protein alpha,
      respectively. In conclusion, glucocorticoid instead of caffeine inhibits bone
      IGF1 expression via glucocorticoid receptor and CCAAT and enhancer binding
      protein alpha and mediates the PCE-induced bone dysplasia and bone mass reduction
      in offspring fetal rats, which may contribute to osteoporosis susceptibility in
      adulthood.

PMID- 30273603
TI  - Reversing CXCL10 Deficiency Ameliorates Kidney Disease in Diabetic Mice.
AB  - The excessive accumulation of extracellular matrix material in the kidney is a
      histopathologic hallmark of diabetic kidney disease that correlates closely with
      declining function. Although considerable research has focused on the role of
      profibrotic factors, comparatively little attention has been paid to the
      possibility that a diminution in endogenous antifibrotic factors may also
      contribute. Among the latter, the ELR- CXC chemokines, CXCL9, CXCL10, and CXCL11,
      have been shown to provide a stop signal to prevent excessive fibrosis. Although
      the plasma concentrations of CXCL9 and CXCL11 were similar, those of CXCL10 were
      markedly lower in diabetic db/db mice compared with control db/m mice. In cell
      culture, CXCL10 inhibited kidney fibroblast collagen production in response to
      high glucose and the prosclerotic growth factor, transforming growth factor-beta.
      In vivo, recombinant murine CXCL10 reduced mesangial and peritubular matrix
      expansion, albuminuria, and glomerular hypertrophy in db/db mice. In bone marrow,
      a major source of circulating chemokines, the concentration of CXCL10 was lower
      in cells derived from diabetic mice than from their nondiabetic counterparts.
      Silencing of CXCR3, the cognate receptor for CXCL10, abrogated the antifibrotic
      effects of bone marrow-derived secretions. In conclusion, experimental diabetes
      is a state of CXCL10 deficiency and that restoration of CXCL10 abundance
      prevented fibrosis and the development of diabetic kidney disease in mice.

PMID- 30273602
TI  - High-Temperature Requirement A 1 Causes Photoreceptor Cell Death in Zebrafish
      Disease Models.
AB  - Age-related macular degeneration (AMD) is an important cause of blindness. It is
      characterized by a retinal pigment epithelium (RPE) disorder that leads to death
      of photoreceptor cells (PRCs). AMD has a strong genetic association with high
      temperature requirement A 1 (HTRA1). The relationship between HTRA1 and the AMD
      phenotype is unknown. In this study, we show that the expression of HTRA1 in
      PRCs, as well as in RPE, is increased by the disease-associated HTRA1 mutation
      and aging. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
      assay and quantitative PCR of apoptosis-associated caspases confirmed that PRC
      specific overexpression of HTRA1 induced PRC death. Transgenic zebrafish
      overexpressing human HTRA1 in rod PRCs showed morphologic changes of the RPE,
      including PRC death and lipofuscin accumulation, features similar to those of
      early AMD. htra1 expression was also increased in a retinitis pigmentosa
      zebrafish model compared with wild type. In both fish lines, PRC death was
      rescued by the suppression of htra1 by the inhibitor 6-boroV. AKT-forkhead box O3
      signaling downstream of HTRA1 was activated via a tumor growth factor beta
      signal, resulting in PRC death. These findings suggest that HTRA1 derived from
      PRCs is associated with early AMD via PRC death. HTRA1 is a potentially effective
      target for neuroprotective therapy of early AMD and other degenerative diseases
      of PRCs.

PMID- 30273605
TI  - Functional Role of microRNAs in the Progression of Breast Ductal Carcinoma in
      situ.
AB  - microRNAs (miRNAs) are small RNAs that influence gene expression by targeting
      messenger RNAs (mRNAs). Depending on the function of their target genes, miRNAs
      may regulate the expression of oncogenes and tumor suppressors, thereby
      contributing to the promotion or inhibition of tumor progression. Ductal
      carcinoma in situ (DCIS), although often diagnosed as breast cancer, is a
      potential precursor to invasive ductal carcinoma. Many of the genetic events
      required for the invasive progression of DCIS occur at the pre-invasive stage,
      and these events include changes to the expression of miRNAs. Aberrant expression
      of miRNAs can influence specific oncogenic or tumor suppressive pathways required
      for breast cancer progression. miRNAs in DCIS have been shown to influence
      hormone signaling, cell-cell adhesion, epithelial to mesenchymal transition, TGF
      beta signaling, maintenance of cancer stem cells, and modulation of the
      extracellular matrix. Additionally, extracellular DCIS miRNAs, such as those
      found in exosomes, may promote invasive progression by modifying the tumor
      microenvironment. Here, we review the miRNAs that have been identified in DCIS
      and how they may contribute to the progression to invasive disease. We also touch
      on the current state of miRNA therapeutic development, including the current
      challenges, and discuss the key future perspectives for research into miRNA
      function for the purpose of miRNA therapeutic development against DCIS.

PMID- 30273604
TI  - Human Placenta Expresses alpha2-Adrenergic Receptors and May Be Implicated in
      Pathogenesis of Preeclampsia and Fetal Growth Restriction.
AB  - alpha2-Adrenergic receptors (alpha2ARs) are G-protein-coupled receptors involved
      in catecholamine signaling by extracellular regulated protein kinase 1 and 2
      (ERK1/2) pathways. We examined placental expression and function of alpha2AR
      subtypes in women with severe preeclampsia (sPE) with and without intrauterine
      growth restriction (IUGR). Placental biopsies were analyzed from 52 women with i)
      sPE (n = 8); ii) sPE + IUGR (n = 9); iii) idiopathic IUGR (n = 8); iv) idiopathic
      preterm birth (n = 16); and v) healthy term controls (n = 11). Expression of
      alpha2AR subtypes (alpha2A, alpha2B, alpha2C) and phospho-ERK1/2 (receptor
      activation marker) was investigated by immunohistochemistry and/or quantitative
      real-time RT-PCR. The effects of alpha2CAR knockdown on syncytialization
      (syncytin-1 and -2) and beta-human chorionic gonadotropin secretion were examined
      in BeWo cells stimulated with forskolin. The effects of alpha2AR agonist UK
      14,304 and specific alpha2CAR antagonist were tested, using a trophoblast
      migration assay. All three alpha2ARs were expressed and functionally active in
      human placenta with site-specific localization. Highest alpha2BAR and alpha2CAR
      mRNA expression was identified in sPE + IUGR. alpha2CAR knockdown increased
      expression of syncytin-1 and -2 but decreased secretion of beta-human chorionic
      gonadotropin. UK 14,304 impaired trophoblast migration. The observed alpha2AR
      expression pattern suggests different function for each subtype. alpha2CAR
      modulates trophoblast syncytialization and migration and may carry pathogenic
      role in sPE + IUGR.

PMID- 30273607
TI  - Profile repeatability: A new method for evaluating repeatability of individual
      hormone response profiles.
AB  - There is broad interest in determining repeatability of individual responses.
      Current methods calculate repeatability of individual points (initial and/or
      peak), time to peak value, or a single measure of the integrated total response
      (area under the curve), rather than the shape of the response profile.
      Repeatability estimates of response profiles using linear mixed models (LMM)
      generate an average repeatability for an aggregate of individuals, rather than an
      estimate of individual repeatability. Here we use a novel ad hoc method to
      calculate repeatability of individual response profiles and demonstrate the need
      for a more rigorous assessment protocol. Response profile repeatability has not
      been defined at the individual level. We do this using a new metric, Profile
      Repeatability (PR), which incorporates components of variance and the degree to
      which response profiles cross each other in a time series. Values range from 0
      (no repeatability) to 1 (complete repeatability). We created synthetic data to
      represent a range of apparent time series repeatability, and 20 independent
      observers visually ranked those data sets by degree of repeatability. We also
      applied the method to real data on stress responses of European starlings Sturnus
      vulgaris. We then computed PR scores for the synthetic data and for real data
      from European starling corticosterone responses over time, and contrast the
      results to those from LMM. Finally, we assessed the sensitivity of PR to
      reductions in the number of time points in the corticosterone response, as well
      as reductions in the number of replicates per individual. We found the average PR
      scores for a group of individuals to be somewhat robust to reductions in points
      in the time series; however, the ranks of individuals (PR values relative to one
      another) could change substantially with reduction in the number of values in a
      time series. PR showed threshold sensitivity to losing replicate time series
      between 6 and 4 replicates. Surprisingly, human observers fell into two disparate
      groups when ranking repeatability of the synthetic data, and the PR score
      indicated that human observers may underestimate repeatability of data where
      replicates cross each other. In contrast to the average profile repeatability
      estimated using LMMs, our approach calculates individual repeatability. From our
      perspective, LMM does not provide a definitive idea of repeatability at the
      individual level; in essence, it concludes that suites of time series with low
      within-individual variance has high repeatability, regardless of replicate
      trajectories. LMM and PR have non-linear relationships between 0 and 1, but PR
      has greater discrimination for mid-values of repeatability. Consistent average
      group repeatability can be associated with substantial differences in individual
      ranks suggests that estimating individual repeatability is critical. The PR score
      should be useful in comparing repeatability of any type of nonlinear, including
      non-monotonic, response profiles over time, which are common in both physiology
      and behavior, and it demonstrates the specific needs for future improvements of a
      profile repeatability metric.

PMID- 30273606
TI  - Adrenals Contribute to Growth of Castration-Resistant VCaP Prostate Cancer
      Xenografts.
AB  - The role of adrenal androgens as drivers for castration-resistant prostate cancer
      (CRPC) growth in humans is generally accepted; however, the value of preclinical
      mouse models of CRPC is debatable, because mouse adrenals do not produce steroids
      activating the androgen receptor. In this study, we confirmed the expression of
      enzymes essential for de novo synthesis of androgens in mouse adrenals, with high
      intratissue concentration of progesterone (P4) and moderate levels of androgens,
      such as androstenedione, testosterone, and dihydrotestosterone, in the adrenal
      glands of both intact and orchectomized (ORX) mice. ORX alone had no effect on
      serum P4 concentration, whereas orchectomized and adrenalectomized (ORX + ADX)
      resulted in a significant decrease in serum P4 and in a further reduction in the
      low levels of serum androgens (androstenedione, testosterone, and
      dihydrotestosterone), measured by mass spectrometry. In line with this, the serum
      prostate-specific antigen and growth of VCaP xenografts in mice after ORX + ADX
      were markedly reduced compared with ORX alone, and the growth difference was not
      abolished by a glucocorticoid treatment. Moreover, ORX + ADX altered the androgen
      dependent gene expression in the tumors, similar to that recently shown for the
      enzalutamide treatment. These data indicate that in contrast to the current view,
      and similar to humans, mouse adrenals synthesize significant amounts of steroids
      that contribute to the androgen receptor-dependent growth of CRPC.

PMID- 30273608
TI  - 3T Multiparametric MRI: Comparison of Performance With and Without Endorectal
      Coil for Prostate Cancer Detection, PI-RADSv2 Category and Staging with Whole
      Mount Histopathology Correlation in 429 Patients.
AB  - PURPOSE: To investigate performance of 3TmpMRI with and without endorectal coil
      (ERC) for detection of prostate cancer (PCa) with whole mount histopathology
      (WMHP) reference. MATERIALS AND METHODS: This retrospective HIPAA-compliant, IRB
      approved case-control study, included patients who underwent 3TmpMRI with and
      without ERC from 7/2009 to 12/2016, prior to prostatectomy. Tumor detection rate
      was calculated for total and index lesions. MRI and histopathology features of
      lesions were compared between two groups. P-value <0.05 was considered
      significant using SPSSv24. RESULTS: 871 WMHP lesions in 429 patients with a mean
      age of 61.8+/-7 were included. ERC and nonERC subcohorts comprised 260 and 169
      patients with 529 and 342 lesions, respectively. Overall tumor detection rates
      for all, ERC and nonERC subcohorts were 49.6% (432/871), 50.5% (267/529) and
      48.2% (165/342), respectively. Index tumor detection rates for overall, ERC and
      nonERC subcohorts were 77.6% (333/429), 78.5% (204/260) and 76.3% (129/169),
      respectively. The ERC and nonERC subcohorts detected 35.9% (66/184) and 48.4%
      (76/157) of anterior lesions (p =0.019), 58% (200/345) and 48.1% (89/185) of
      posterior lesions (p=0.025), 37.3% (41/110) and 54.4% (62/114) of transition
      lesions (p=0.010) and 53.7% (225/419) and 45.2% (103/228) of peripheral lesions
      (p=0.033). After adjusting for clinical and pathological factors, the ERC group
      only showed higher detection for peripheral and posterior PCa lesions.
      CONCLUSIONS: 3TmpMRI with and without ERC had similar detection for overall and
      index PCa. However, ERC subcohort had significantly higher detection of posterior
      and peripheral and lower detection of anterior and transition PCa lesions.

PMID- 30273609
TI  - Role of Residual Fragments on the Risk of Repeat Surgery After Flexible
      Ureteroscopy and Laser Lithotripsy: Single Center Study.
AB  - PURPOSE: To analyze the impact of residual stone fragments seen on abdominal X
      ray (KUB) after ureteroscopy and laser lithotripsy (URS) on the risk of repeat
      surgical intervention. MATERIALS AND METHODS: Our study included 781 patients
      (802 renal units) who had URS with laser lithotripsy, KUB within 3 months
      postoperatively and at least 1 year of follow-up. The URSs were performed using
      dusting technique. We analyzed the association between the surgical recurrence
      free survival and the size of the largest residual fragment. RESULTS: Over a
      median follow-up of 4.2 years repeat surgery was performed on 161 (20%) renal
      units. 75% of repeat interventions were performed for symptomatic
      nephrolithiasis. Postoperative imaging showed residual stone fragments in 42% of
      cases. In the entire group the risk of repeat surgery was increased in renal
      units with residual fragments >2 mm. The effect of the size of residual fragments
      on the risk of surgical recurrence varied by patient's body mass index (BMI) and
      was much larger in non-obese subjects who had increased risk of repeat surgery
      with residual fragments of any size. In the obese subgroup only >2 mm fragments
      increased the risk of surgical recurrence. CONCLUSIONS: The association between
      the size of residual stone fragments detected by post-URS KUB and the risk of
      repeat surgical intervention depends on patients' BMI. Non-obese patients with
      residual stone fragments of any size have increased risk of repeat intervention
      compared to those with negative KUB. The predictive value of post-URS KUB in
      obese patients is limited.

PMID- 30273610
TI  - A multi-amplicon 16S rRNA sequencing and analysis method for improved taxonomic
      profiling of bacterial communities.
AB  - Metagenomic sequencing of bacterial samples has become the gold standard for
      profiling microbial populations, but 16S rRNA profiling remains widely used due
      to advantages in sample throughput, cost, and sensitivity even though the
      approach is hampered by primer bias and lack of specificity. We hypothesized that
      a hybrid approach, that combined targeted PCR amplification with high-throughput
      sequencing of multiple regions of the genome, would capture many of the
      advantages of both approaches. We developed a method that identifies and
      quantifies members of bacterial communities through simultaneous analysis of
      multiple variable regions of the bacterial 16S rRNA gene. The method combines
      high-throughput microfluidics for PCR amplification, short read DNA sequencing,
      and a custom algorithm named MVRSION (Multiple 16S Variable Region Species-Level
      IdentificatiON) for optimizing taxonomic assignment. MVRSION performance was
      compared to single variable region analyses (V3 or V4) of five synthetic mixtures
      of human gut bacterial strains using existing software (QIIME), and the results
      of community profiling by shotgun sequencing (COPRO-Seq) of fecal DNA samples
      collected from gnotobiotic mice colonized with a defined, phylogenetically
      diverse consortium of human gut bacterial strains. Positive predictive values for
      MVRSION ranged from 65%-91% versus 44%-61% for single region QIIME analyses (p <
      .01, p < .001), while the abundance estimate r2 for MVRSION compared to COPRO-Seq
      was 0.77 vs. 0.46 and 0.45 for V3-QIIME and V4-QIIME, respectively. MVRSION
      represents a generally applicable tool for taxonomic classification that is
      superior to single-region 16S rRNA methods, resource efficient, highly scalable
      for assessing the microbial composition of up to thousands of samples
      concurrently, with multiple applications ranging from whole community profiling
      to targeted tracking of organisms of interest in diverse habitats as a function
      of specified variables/perturbations.

PMID- 30273611
TI  - Exercise-related resuscitated out-of-hospital cardiac arrest due to presumed
      myocardial ischemia: Result from coronary angiography and intravascular
      ultrasound.
AB  - AIM: Possible causes of exercise-related out-of-hospital cardiac arrest (OHCA) in
      people with coronary artery disease (CAD) include atherosclerotic plaque rupture
      (PR) and intra-coronary thrombosis, exercise-induced myocardial ischaemia and
      other triggers. We investigated whether there are differences in the incidence of
      PR and/or intra-coronary thrombus and in clinical outcome between 'exercise
      related' and 'non-exercise-related' OHCA. METHODS: 219 consecutive resuscitated
      patients with CAD diagnosed by emergency coronary angiography (CAG) were
      enrolled. They were divided into the exercise group (>=6 METs; n = 35) and non
      exercise group (<6 METs; n = 184), according to estimated METs immediately before
      OHCA using 2011 Compendium of Physical Activities. We investigated whether
      culprit lesions had PR and/or thrombus using CAG and intravascular ultrasound.
      The clinical outcome was 30-day survival with minimal neurologic impairment.
      RESULTS: Acute PR and/or thrombus occurred in fewer of the exercise group than
      the non-exercise group (11% vs. 90%; P < 0.001). The exercise group had a higher
      incidence of favorable neurological outcome (94% vs. 47%; P < 0.001) than the non
      exercise group. Multivariable Cox proportional hazards models revealed that
      exercise immediately before OHCA was one of the predictors of a good neurological
      outcome (HR, 0.19; P = 0.025). CONCLUSION: The incidence of PR and/or thrombosis
      was lower in the group taking higher levels of exercise, than in the group taking
      less or no exercise. "Exercise-related" OHCA with CAD has better clinical
      outcomes than "non-exercise-related" with a greater proportion of witnessed
      arrests and early return of spontaneous circulation.

PMID- 30273612
TI  - Low Intensity Pulsed Ultrasound Influences the Myogenic Differentiation of Muscle
      Satellite Cells in a Stress Urinary Incontinence Rat Model.
AB  - OBJECTIVE: To investigate the therapeutic effect of low intensity pulsed
      ultrasound (LIPUS) in a stress urinary incontinence (SUI) rat model and its
      influence on myogenic satellite cells. METHODS: Fifty Sprague-Dawley rats
      underwent vaginal distension and bilateral ovariectomy mimicking partum injury
      and menopause to construct SUI models, which were further randomized into 100
      mW/cm2 LIPUS, 200 mW/cm2 LIPUS, 300 mW/cm2 LIPUS, and none-treatment control
      subgroups with 10 rats per subgroup. Ten rats served as mock operation control.
      Leak point pressure and bladder capacity were recorded 1 week after LIPUS
      treatment. Immunofluorescence staining and Western blot were performed to examine
      histological changes, myodifferentiation, and signaling pathway. RESULTS: Here,we
      found the leak point pressure and bladder capacity were restored in 200 mW/cm2
      LIPUS and 300 mW/cm2 LIPUS groups, but not in 100 mW/cm2 LIPUS group. More robust
      striated muscle regeneration was observed in 200 mW/cm2 LIPUS group comparing
      with the SUI none-treatment group. Moreover, we found LIPUS activated the
      myodifferentiation of muscle satellite cells, which is correlated to p38
      phosphorylation level. CONCLUSION: LIPUS restored the leak point pressure and
      bladder capacity, and activated satellite cell myodifferentiation in SUI rat
      model.

PMID- 30273613
TI  - A Prospective Accuracy Study of Prostate Imaging Reporting and Data System
      Version 2 on Multiparametric Magnetic Resonance Imaging in Detecting Clinically
      Significant Prostate Cancer With Whole-mount Pathology.
AB  - OBJECTIVE: To assess the accuracy of Prostate Imaging Reporting and Data System
      version 2 (PI-RADS v2) in detecting clinically significant prostate cancer
      (csPCa) on multiparametric magnetic resonance imaging (mpMRI) using whole-mount
      sections after radical prostatectomy (RP) as reference standard. METHODS: Forty
      eight patients undergoing mpMRI before RP were prospectively enrolled. Two
      experienced radiologists independently scored and mapped imaging findings
      according to PI-RADS v2. One experienced uropathologist mapped cancers detected
      on whole-mount sections using the PI-RADS v2 sector scheme. Per-lesion and per
      patient analyses were run. Primary outcomes were sensitivity and false discovery
      rate (FDR) in detecting csPCa using PI-RADS v2 score >=3 and >=4 as thresholds.
      Secondary outcome was inter-reader agreement. RESULTS: On the per-lesion
      analysis, sensitivity and FDR at the PI-RADS v2 threshold score >=3 were 0.75 and
      0.17 for Reader 1, and 0.67 and 0.13 for Reader 2, respectively. At the PI-RADS
      v2 threshold score >=4, sensitivity was slightly lower, and FDR nearly halved for
      both readers. On the per-patient analysis, sensitivity for csPCa at the PI-RADS
      v2 threshold score >=3 was 0.85 for Reader 1, and 0.78 for Reader 2. At the PI
      RADS v2 threshold score >=4, sensitivity was slightly lower for both readers.
      Inter-reader agreement was substantial (k 0.72 and 0.65 for PI-RADS v2 threshold
      score >=3 and >=4, respectively). CONCLUSION: In our prospective study with
      pathology after RP as standard of reference, PI-RADS v2 showed good sensitivity
      in detecting csPCa on mpMRI with substantial agreement between 2 experienced
      readers. Threshold score >=4 had lower FDR.

PMID- 30273614
TI  - Spatial memory in young adults: Gender differences in egocentric and allocentric
      performance.
AB  - Spatial memory allows us to locate objects and organisms in space and move
      through the environment. We frequently use two strategies for this purpose:
      egocentric, related to the viewer's perspective, and allocentric, associated with
      environmental cues. This ability is usually assessed by 2D or virtual reality
      based tasks. Gender differences have been reported on these tasks. We designed
      two card-placing tasks with the aim of assessing egocentric and allocentric
      spatial memory in a real environment. This task makes it possible to separately
      compare egocentric and allocentric strategies, providing participants with 3D
      information naturally present in daily orientation activities. We will assess the
      performance of male and female young adults on the two strategies. Ninety-four
      subjects were recruited and performed egocentric and allocentric spatial memory
      card placing tasks. Spatial Span, forward and backward, was also assessed using
      the Cambridge Neuropsychological Assessment Battery (CANTAB), and the brief
      version of Benton's Judge of Line Orientation Test (JoLO) was used to evaluate
      the ability to judge spatial relations. Our results show that men outperformed
      women on both spatial memory tasks. Women performed better on Allocentric tasks
      than on Egocentric tasks, whereas men's scores did not show differences between
      strategies. Spatial memory performance on the card placing tasks was
      significantly correlated with performance on the backward visuospatial span from
      the CANTAB. This study supports the existence of gender differences in spatial
      memory functioning, and it provides novel tools for the neuropsychological
      assessment of spatial memory.

PMID- 30273615
TI  - Coarse-grained dynamics of supramolecules: Conformational changes in outer shells
      of Dengue viruses.
AB  - While structural data on viruses are more and more common, information on their
      dynamics is much harder to obtain as those viruses form very large molecular
      complexes. In this paper, we propose a new method for computing the coarse
      grained normal modes of such supra-molecules, NormalGo. A new formalism is
      developed to represent the Hessian of a quadratic potential using tensor
      products. This formalism is applied to the Tirion elastic potential, as well as
      to a Go like potential. When combined with a fast method for computing a select
      set of eigenpairs of the Hessian, this new formalism enables the computation of
      thousands of normal modes of a full viral shell with more than one hundred
      thousand atoms in less than 2 h on a standard desktop computer. We then compare
      the two coarse-grained potentials. We show that, despite significant differences
      in their formulations, the Tirion and the Go like potentials capture very similar
      dynamics characteristics of the molecule under study. However, we find that the
      Go like potential should be preferred as it leads to less local deformations in
      the structure of the molecule during normal mode dynamics. Finally, we use
      NormalGo to characterize the structural transitions that occur when FAB fragments
      bind to the icosahedral outer shell of serotype 3 of the Dengue virus. We have
      identified residues at the surface of the outer shell that are important for the
      transition between the FAB-free and FAB-bound conformations, and therefore
      potentially useful for the design of antibodies to Dengue viruses.

PMID- 30273616
TI  - Chronic whole-body heat treatment relieves atherosclerotic lesions,
      cardiovascular and metabolic abnormalities, and enhances survival time restoring
      the anti-inflammatory and anti-senescent heat shock response in mice.
AB  - Unhealthy lifestyle persistently feeds forward inflammation in metabolic organs
      thus imposing senescence-associated secretory phenotype (SASP), as observed in
      obesity and type 2 diabetes. However, SASP blocks physiological resolution of
      inflammation by suppressing the anti-inflammatory and anti-senescent heat shock
      (HS) response, i.e., the gene program centered in heat shock factor-1 (HSF1)
      dependent expression heat shock proteins (HSPs). As SASP-inducing factors are not
      removed, leading to the perpetuation of inflammation, we argued that SIRT1-HSF1
      HSP axis might also be suppressed in atherosclerosis, which could be reversible
      by heat treatment (HT), the most powerful HS response trigger. LDLr-/- adult mice
      were fed on high-fat/high-cholesterol diet from the age of 90 days until the end
      of study (age of 270 days). After 120 days under atherosclerotic diet, the
      animals were submitted to either whole-body HT (n = 42; 40  degrees C) or sham (n
      = 59; 37  degrees C) treatment (15 min/session), under anesthesia, once a week,
      for 8 weeks, being echographically and metabolically monitored. Aortic
      expressions of SIRT1, HSF1, HSP27, HSP72 and HSP73 were progressively depressed
      in atherosclerotic animals, as compared to normal (LDLr+/+; n = 25) healthy
      counterparts, which was paralleled by increased expression of NF-kappaB-dependent
      VCAM1 adhesion molecule. Conversely, HT completely reversed suppression of the
      above HS response proteins, while markedly inhibiting both VCAM1 expression and
      NF-kappaB DNA-binding activity. Also, HT dramatically reduced plasma levels of
      TG, total cholesterol, LDL-cholesterol, oxidative stress, fasting glucose and
      insulin resistance while rising HDL-cholesterol levels. HT also decreased body
      weight gain, visceral fat, cellular infiltration and aortic fatty streaks, and
      heart ventricular congestive hypertrophy, thereby improving aortic blood flow and
      myocardial performance (Tei) indices. Remarkably, heat-treated mice stopped dying
      after the third HT session (= 8 human years), suggesting a curative effect.
      Therefore, evolution of atherosclerosis is associated with suppression of the
      anti-inflammatory and anti-senescent SIRT1-HSF1-HSP molecular axis, which is
      refreshed by chronic heat treatment.

PMID- 30273617
TI  - Animal models for analysis of immunological responses to nanomaterials:
      Challenges and considerations.
AB  - Nanotechnology provides many solutions to improve conventional drug delivery and
      has a unique niche in the areas related to the specific targeting of the immune
      system, such as immunotherapies and vaccines. Preclinical studies in this field
      rely heavily on the combination of in vitro and in vivo methods to assess the
      safety and efficacy of nanotechnology platforms, nanoparticle-formulated drugs,
      and vaccines. While certain types of toxicities can be evaluated in vitro and
      good in vitro-in vivo correlation has been demonstrated for such tests, animal
      studies are still needed to address complex biological questions and, therefore,
      provide a unique contribution to establishing nanoparticle safety and efficacy
      profiles. The genetic, metabolic, mechanistic, and phenotypic diversity of
      currently available animal models often complicates both the animal choice and
      the interpretation of the results. This review summarizes current knowledge about
      differences in the immune system function and immunological responses of animals
      commonly used in preclinical studies of nanomaterials. We discuss challenges,
      highlight current gaps, and propose recommendations for animal model selection to
      streamline preclinical analysis of nanotechnology formulations.

PMID- 30273618
TI  - Fixation probabilities and hitting times for low levels of frequency-dependent
      selection.
AB  - In population genetics, diffusions on the unit interval are often used to model
      the frequency path of an allele. In this setting we derive approximations for
      fixation probabilities, expected hitting times and the expected frequency
      spectrum for low levels of frequency-dependent selection. Specifically, we
      rederive and extend the one-third rule of evolutionary game theory (Nowak et al.,
      2004) and effects of stochastic slowdown (Altrock and Traulsen, 2009). Since
      similar effects are of interest in other application areas, we formulate our
      results for general one-dimensional diffusions.

PMID- 30273619
TI  - Dynamic suspension culture improves ex vivo expansion of cytokine-induced killer
      cells by upregulating cell activation and glucose consumption rate.
AB  - Ex vivo expansion is an effective strategy to acquire cytokine-induced killer
      (CIK) cells needed for clinical trials. In this work, the effects of dynamic
      suspension culture, which was carried out by shake flasks on a shaker, on CIK
      cells were investigated by the analysis of expansion characteristics and
      physiological functions, with the objective to optimize the culture conditions
      for ex vivo expansion of CIK cells. The results showed that the expansion folds
      of total cells in dynamic cultures reached 69.36 +/- 30.36 folds on day 14, which
      were significantly higher than those in static cultures (9.24 +/- 1.12 folds, P <
      0.05), however, the proportions of CD3+ cells and CD3+CD56+ cells in both
      cultures were similar, leading to much higher expansion of CD3+ cells and
      CD3+CD56+ cells in dynamic cultures. Additionally, expanded CIK cells in two
      cultures possessed comparable physiological functions. Notably, significantly
      higher percentages of CD25+ cells and CD69+ cells were found in dynamic cultures
      (P <  0.05). Besides, much higher glucose consumption rate of cells (P <  0.05)
      but similar YLac/gluc were observed in dynamic cultures. Further, cells in
      dynamic cultures had better glucose utilization efficiency. Together, these
      results suggested that dynamic cultures improved cell activation, then
      accelerated glucose consumption rate, which enhanced cell expansion and promoted
      glucose utilization efficiency of cells.

PMID- 30273620
TI  - Hypothesis-driven weight-of-evidence analysis for the endocrine disruption
      potential of benzene.
AB  - Exposure to benzene has many sources, from gasoline refueling to tobacco
      combustion. Although the toxicology of benzene is well studied, the potential for
      environmental exposure and a heightened interest in identifying substances that
      may cause toxicity by interacting with the endocrine systems of humans and
      wildlife resulted in benzene being placed on the second list of chemicals for
      possible screening under the USEPA's Endocrine Disruptor Screening Program.
      Therefore, we conducted a thorough, systematic literature search and used a
      weight-of-evidence methodology to test hypotheses regarding the potential for
      benzene to act via estrogen, androgen, thyroid, and steroidogenic pathways. The
      methodology included an assessment of data quality and a semi-quantitative
      weighting of endocrine-responsive endpoints measured in various types of studies
      according to their relevance for evaluating each hypothesis. This maximized use
      of all relevant and reliable literature on benzene and enabled a transparent
      comparison of evidence supporting and opposing each hypothesized mode of action.
      While benzene affected reproductive organ weights and histopathology in a few
      studies, there was no consistent pattern of effects suggestive of an estrogen,
      androgen, thyroid or steroidogenic mode of action. Based on data from multiple
      animal species, benzene appears to lack endocrine activity by these pathways.

PMID- 30273621
TI  - Cost-Effectiveness Analysis of Descemet's Membrane Endothelial Keratoplasty
      Versus Descemet's Stripping Endothelial Keratoplasty in the United States.
AB  - PURPOSE: To determine the cost-effectiveness of Descemet's membrane endothelial
      keratoplasty (DMEK) compared with Descemet's stripping automated endothelial
      keratoplasty (DSAEK) in the United States. DESIGN: Cost-effectiveness analysis in
      a surgical center in the United States. PARTICIPANTS: Binocular adult patient
      undergoing endothelial keratoplasty. METHODS: A base case of a 70-year-old man
      undergoing his first endothelial keratoplasty for bilateral Fuchs' endothelial
      dystrophy. The cost-effectiveness of DMEK was compared with DSAEK over a 15-year
      time horizon. The incidences and costs of complications were derived from PubMed
      English literature searches, Medicare reimbursements, and average wholesale
      prices. All costs were discounted 3% per annum and adjusted for inflation to 2018
      U.S. dollars. Uncertainty was evaluated using deterministic and probabilistic
      sensitivity analyses. MAIN OUTCOME MEASURES: Incremental cost-effectiveness
      ratios and incremental cost-utility ratios, measured in cost per quality-adjusted
      life-years (QALYs). RESULTS: Performing a DMEK instead of a DSAEK generated an
      extra 0.4 QALYs over a 15-year period. From a societal and third-party payer
      perspective, DMEK was cost-saving when compared with DSAEK in improving visual
      acuity in the base case. Probabilistic sensitivity analyses with variations in
      the costs and rebubble rates revealed that DMEK was cost-saving compared with
      DSAEK in 38% of iterations and was within a societal willingness-to-pay threshold
      of $50 000 in 98% of models. CONCLUSIONS: From the societal and third-party payer
      perspectives in the United States, DMEK generated greater utilities and was less
      costly than DSAEK. Therefore, DMEK was the dominant procedure and was cost-saving
      with respect to DSAEK. The economic model was robust based on sensitivity
      analyses.

PMID- 30273623
TI  - PCR cycle threshold to assess a diagnostic stewardship intervention for C.
      difficile testing.

PMID- 30273622
TI  - Are Patient Self-Reported Outcome Measures Sensitive Enough to Be Used as End
      Points in Clinical Trials?: Evidence from the United Kingdom Glaucoma Treatment
      Study.
AB  - PURPOSE: The United Kingdom Glaucoma Treatment Study (UKGTS) demonstrated the
      effectiveness of an intraocular pressure-lowering drug in patients with glaucoma
      using visual field progression as a primary outcome. The present study tested the
      hypothesis that responses on patient-reported outcome measures (PROMs; secondary
      outcome measure) differ between patients receiving a topical prostaglandin analog
      (latanoprost) or placebo eye drops in UKGTS. DESIGN: Multicenter, randomized,
      triple-masked, placebo-controlled trial. PARTICIPANTS: Newly diagnosed glaucoma
      patients in the UKGTS with baseline and exit PROMs (n = 182 and n = 168 patients
      from the treatment and placebo groups, respectively). METHODS: In the UKGTS
      (trial registration number, ISRCTN96423140), patients with open-angle glaucoma
      were allocated to receive latanoprost (treatment) or placebo; the observation
      period was 24 months. Patients completed general health PROMs (European Quality
      of Life in 5 Dimensions [EQ-5D] and 36-item Short Form [SF-36]) and PROMs
      specific to glaucoma (15-item Glaucoma Quality of Life [GQL-15] and 9-item
      Glaucoma Activity Limitation [GAL-9]) at baseline and exit from the trial.
      Percentage changes between measurement on PROMs were calculated for each patient
      and compared between treatment arms. In addition, differences between stable
      patients (n = 272) and those with glaucomatous progression (n = 78), as
      determined by visual field change (primary outcome), were assessed. MAIN OUTCOME
      MEASURE: PROMs on health-related and vision-related quality of life. RESULTS:
      Average percentage change on PROMs was similar for patients in both arms of the
      trial, with no statistically significant differences between treatment and
      placebo groups (EQ-5D, P = 0.98; EQ-5D visual analog scale, P = 0.88; SF-36, P =
      0.94, GQL-15, P = 0.66; GAL-9, P = 0.87). There were statistically significant
      differences between stable and progressing patients on glaucoma-specific PROMs
      (GQL-15, P = 0.02; GAL-9, P = 0.02), but not on general health PROMs (EQ-5D, P =
      0.62; EQ-5D visual analog scale, P = 0.23; SF-36, P = 0.65). CONCLUSIONS: Average
      change in PROMs on health-related and vision-related quality of life was similar
      for the treatment and placebo groups in the UKGTS. The PROMs used may not be
      sensitive enough to function as primary end points in clinical trials when
      participants have newly diagnosed early-stage glaucoma.

PMID- 30273624
TI  - Evolutionary Divergence of Brain-specific Precursor miRNAs Drives Efficient
      Processing and Production of Mature miRNAs in Human.
AB  - The hallmark of human evolution encompasses the dramatic increase in brain size
      and complexity. The intricate interplays of micro-RNAs (miRNAs) and their target
      genes are indispensable in brain development. Sequence divergence in distinct
      structural regions of Brain-specific precursor miRNAs (pre-miRNAs) and its
      consequence in the production of corresponding mature miRNAs in human are
      unknown. To address these questions, first we classified miRNAs into three
      categories based on tissue expression: Brain-specific (expressed exclusively in
      brain), Non-brain (expressed in Non-brain tissues) and Common (expressed in all
      tissues) and compared the sequence divergence of different structural regions
      (basal segment, lower and upper stem, internal and terminal loop) of categorized
      pre-miRNAs across human, non-human primates and rodents. Our analysis revealed
      that unpaired regions of Brain-specific pre-miRNAs in human bear traces of
      relatively high rate of evolutionary divergence compared to those in other
      species. Cross-tissue expression analysis unveiled the higher expression of the
      Brain-specific miRNAs in human compared to other species. Intriguingly, in human
      brain, expression levels of these miRNAs superseded the levels of the
      ubiquitously expressed "Common-miRNAs". Further analysis revealed that presence
      of certain motif and nucleotide preference in the Brain-specific pre-miRNAs may
      favor DROSHA and DICER to ameliorate miRNA processing. The higher processing
      efficiency of human Brain-specific miRNAs was reflected as an elevated production
      of corresponding mature miRNAs in the human brain. Finally, re-construction of
      gene-regulatory network uncovers different pathways driven by Brain-specific
      miRNAs that may contribute to the development of brain in human.

PMID- 30273625
TI  - New Insight into the Mechanism of Mannitol Effects on Cerebrospinal Fluid
      Pressure Decrease and Craniospinal Fluid Redistribution.
AB  - Intracranial hypertension, which often follows a severe brain injury, is usually
      treated with intravenous (i.v.) application of hyperosmolar solutions. The
      mechanism of intracranial cerebrospinal fluid (CSF) pressure decrease after such
      a treatment is still unclear. The aim of this article was to try to explain the
      mechanism of CSF pressure reduction after i.v. hyperosmolar mannitol bolus in
      regard to the changes in CSF volume. Two types of experiments were done on
      anesthetized cats before and after hyperosmolar mannitol application: ventriculo
      cisternal perfusion at different perfusion rates, simultaneously measuring the
      perfusate outflow volume, and CSF pressure recording in the lateral ventricle
      before and during artificial CSF infusion. Mannitol application in the first
      group of cats significantly reduced collected prefusate volume during ventriculo
      cisternal perfusion, and in the second group it prevented CSF pressure increase
      caused by artificial CSF infusion. Our results strongly suggest that the
      mechanism of hyperosmolar mannitol action after its i.v. application is based on
      osmotic fluid retrieval from interstitial and cerebrospinal compartments into the
      microvessels. This shift, without significant volume change inside the cranium,
      causes a predominant decrease of CSF volume in the spinal part of the system,
      which in turn leads to lowering of the CSF pressure. Spinal CSF volume decrease
      is enabled by the extensibility of the spinal dura, this way providing the
      possibility for CSF volume redistribution inside the CSF system, together with
      CSF pressure decrease. This mechanism of mannitol action is in accordance with
      the new hypothesis of CSF physiology.

PMID- 30273626
TI  - Mesolimbic connectivity signatures of impulsivity and BMI in early adolescence.
AB  - Across age groups, differences in connectivity of the mesolimbic and the
      prefrontal cortex co-vary with trait impulsivity and sensation-seeking.
      Impulsivity and sensation-seeking are also known to increase during early
      adolescence as maturation of subcortical structures outpaces that of the
      prefrontal cortex. While an imbalance between the striatum and prefrontal cortex
      is considered a normal developmental process, higher levels of adolescent
      impulsivity and sensation-seeking are associated with an increased risk for
      diverse problems, including obesity. To determine how the relationship between
      sensation-seeking, impulsivity and body mass index (BMI) is related to shared
      neural correlates we measured their relationships with the connectivity of nuclei
      in the striatum and dopaminergic midbrain in young adolescents. Data were
      collected from 116 children between the ages of 12 and 14, and included resting
      state functional magnetic resonance imaging, personality measures from the
      Substance Use Risk Profile Scale, and BMI Z-score for age. The shared variance
      for the connectivity of regions of interest in the substantia nigra, ventral
      tegmental area, ventral striatum and sub-thalamic nucleus, personality measures
      and BMI Z-score for age, were analyzed using partial least squares correlation.
      This analysis identified a single significant striato-limbic network that was
      connected with the substantia nigra, ventral tegmental area and sub-thalamic
      nuclei (p = 0.002). Connectivity within this network which included the
      hippocampi, amygdalae, parahippocampal gyri and the regions of interest,
      correlated positively with impulsivity and BMI Z-score for age and negatively
      with sensation-seeking. Together, these findings emphasize that, in addition to
      the well-established role that frontostriatal circuits play in the development of
      adolescent personality traits, connectivity of limbic regions with the striatum
      and midbrain also impact impulsivity, sensation-seeking and BMI Z-score in
      adolescents.

PMID- 30273627
TI  - Nitric oxide and l-arginine regulate feeding in satiated rats.
AB  - Nitric Oxide (NO) and its precursor l-arginine were found to inhibit feeding in
      rats with a low motivation to eat, as they do in Aplysia. In rats that are
      relatively satiated, treatment with an NO blocker increased feeding, and
      treatment with an NO donor or with either of 2 doses of l-arginine inhibited
      feeding. NO and l-arginine modulated several parameters of feeding, such as the
      total duration of appetitive behaviors, the time spent feeding, the quantity of
      food eaten and the number of feeding bouts. The inhibitory effect of l-arginine
      on feeding could not be attributed to changes in locomotion. These data indicate
      that satiation is partially mediated by increased production of NO. NADPH
      Diaphorase histochemical staining, which is specific for tissues actively
      producing NO, showed significantly greater staining in satiated compared to
      hungry rats in all 4 hypothalamic nuclei (paraventricular and arcuate nuclei,
      lateral and ventromedial hypothalamus) that were examined. l-arginine may act as
      a regulator of feeding by controlling NO production in several hypothalamic
      nuclei, specifically under condition of a low feeding motivation.

PMID- 30273628
TI  - Gulf War agents pyridostigmine bromide and permethrin cause hypersensitive
      nociception that is restored after vagus nerve stimulation.
AB  - Gulf war illness (GWI) is a chronic multi-symptom disease that afflicts 25-33% of
      troops that were deployed in the 1990-1991 Gulf War. GWI symptoms include
      cognitive, behavioral and emotional deficits, as well as migraines and pain. It
      is possible that exposure to Gulf War agents and prophylactics contributed to the
      reported symptomology. Pyridostigmine bromide (PB) and permethrin (PER) were
      given to protect from nerve gas attacks and insect vector born disease,
      respectively. Previous studies have demonstrated that 10 days of exposure to
      these chemicals can cause symptoms analogous to those observed in GWI, including
      impairment of long-term memory in mice. Other studies using this model have shown
      chronic neuroinflammation, and chronic neuroinflammation can lead to altered
      nociceptive sensitivity. At 10-weeks after the 10-day PB and PER exposure
      paradigm, we observed lowered nociceptive threshold on the Von Frey test that was
      no longer evident at 28 weeks and 38 weeks post-exposure. We further determined
      that vagus nerve stimulation, initiated at 38 weeks after exposure, restores the
      lowered nociceptive sensitivity. Therefore, stimulating the vagus nerve appears
      to influence nociception. Future studies are need to elucidate possible
      mechanisms of this effect.

PMID- 30273629
TI  - Fluoride activates microglia, secretes inflammatory factors and influences
      synaptic neuron plasticity in the hippocampus of rats.
AB  - Epidemiological studies have reported that highly fluoridated drinking water may
      significantly decrease the Intelligence Quotient (IQ) of exposed children. It is
      thought that synaptic plasticity is the basis of learning and memory skills in
      developing children. However, the effect on synaptic plasticity by activated
      microglia induced via fluoride treatment is less clear. Our previous research
      showed that fluoride ions activated microglia which then released pro
      inflammatory cytokines. In this study, hippocampal-dependent memory status was
      evaluated in rat models sub-chronically exposed to fluoride in their drinking
      water. Microglial activation in the hippocampus was examined using
      immunofluorescence staining and the expression of synaptophysin (SYP) and
      postsynaptic density protein 95 (PSD-95), Long-term potentiation (LTP) and the
      expression of Amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) receptor
      subunit GluR2 as well as N-methyl-d-aspartate (NMDA) receptor subunit NMDAR2beta
      of exposed rats. We found that fluoride exposure activated microglia and
      increased the expression of DAP12 and TREM2, as well as promoted pro-inflammatory
      cytokines secretion via ERK/MAPK and P38/MAPK signal pathways. Furthermore
      fluoride depressed LTP and decreased PSD-95 protein levels as well as expression
      of ionotropic glutamate receptors GluR2 and NMDAR2beta. We concluded that the
      role of fluoride on synaptic plasticity may be associated with neuroinflammation
      induced by microglia.

PMID- 30273630
TI  - The alternatively spliced porcine FcgammaRI regulated PRRSV-ADE infection and
      proinflammatory cytokine production.
AB  - Receptors for the Fc region of IgG (FcgammaRs) play a key role in protecting the
      immune system and host from infection. In this study, we described the cloning,
      sequencing and characterization of porcine FcgammaRI, and reported six different
      FcgammaRI isoforms, four of which have never been reported before. Further
      analysis revealed that FcgammaR isoforms are generated by alternative splicing
      mechanisms, including two membrane isoforms and four soluble isoforms.
      Importantly, we found FcgammaRI splice variants differentially influence PRRSV
      antibody-dependent enhancement (ADE) effects. Membrane pCD64-T1 promotes
      endocytosis of the PRRSV-antibody complex to enhance PRRSV replication, and
      soluble pCD64-T3 has no ADE effect on PRRSV proliferation, but shows an
      inflammation enhancement effect. The differential expression of selective
      splicing in primary PAM cells and 3D4/21 cell lines are altered and regulated by
      PRRSV infection and inflammatory environment. Our results indicated that porcine
      FcgammaRI plays dual regulatory roles in PRRSV multiplication and PRRSV
      inflammation process by the alternatively spliced mechanism, which will be a new
      target in PRRSV prevention and control.

PMID- 30273631
TI  - Carotid webs and ischemic stroke: Experiences in a comprehensive stroke center.
AB  - BACKGROUND AND PURPOSE: Carotid webs are intraluminal filling defects at the
      carotid bulb which are considered rare, though possibly underappreciated entities
      with recent studies demonstrating a likely casual association with ischemic
      stroke. The purpose of the study is to describe our recent experience with
      clinical and imaging manifestations of carotid webs. MATERIALS AND METHODS: A
      retrospective review of CTA neck studies in all adult patients presenting to our
      institution during the 19-month study interval was performed to determine the
      presence of carotid webs. Subsequent chart review of these patients with webs was
      performed to assess their clinical history and to obtain demographic detail.
      RESULTS: A total of 14 patients were identified with carotid webs in the study
      population. The mean age of patients with webs was 42.1 years (range: 28-54),
      consisting mostly of African Americans (86%) and females (64%). Ten (71%) of web
      patients had a history of ischemic stroke, each ipsilateral to the side of web,
      and at least four of these patients had recurrent ischemic stroke. CONCLUSION: We
      provide one of the largest sample sizes of webs gathered in a single study. Given
      its association with ischemic stroke, carotid webs should be assessed for in all
      patients presenting with ischemic stroke, especially younger African Americans.

PMID- 30273632
TI  - Review on rosmarinic acid extraction, fractionation and its anti-diabetic
      potential.
AB  - Rosmarinic acid is a bioactive phytochemical that can be found in many herbs as
      ethnomedicines. It possesses remarkable pharmacological activities, and thus
      leading to its exploration as a therapeutic drug in diabetes treatment recently.
      This article reviews the extraction and fractionation techniques for plant-based
      natural rosmarinic acid and its anti-diabetic potential based on literature data
      published in journals, books, and patents from 1958 to 2017. Factors affecting
      the performance of rosmarinic acid extraction and fractionation such as operating
      temperature, time, solvent to sample ratio and eluent system are compiled and
      discussed in detail. The inhibitory action of rosmarinic acid against sugar
      digestive enzymes, and protective action towards pancreatic beta-cell dysfunction
      and glucolipotoxicity mediated oxidative stress are also critically reviewed. The
      optimal parameters are largely dependent on the applied extraction and
      fractionation techniques, as well as the nature of plant samples. Previous
      studies have proven the potent role of rosmarinic acid to control plasma glucose
      level and increase insulin sensitivity in hyperglycemia. Although rosmarinic acid
      is readily absorbed by human body, its mechanism after consumption is remained
      unclear. Intensive studies should be well planned to determine the dosage and
      toxicity level of rosmarinic acid for efficacy and safe consumption.

PMID- 30273633
TI  - A likely placental barrier against methylmercury in pregnant rats exposed to fish
      containing diets.
AB  - Methylmercury (MeHg) taken up through fish consumption can be transferred from
      the mother to the fetus during pregnancy. In the present study, pregnant rat
      mothers were contaminated with environmentally relevant doses of 36 and 76 ng
      MeHg/g of food using diets containing naturally mercury-containing fish. Young
      female rats fed with fish-containing food after weaning showed decreased
      locomotion in Y maze for accumulated concentrations in brain as low as 75 ng Hg/g
      dry weight (15 ng Hg/g wet weight). Young female rats fed the control diet after
      weaning yet borne by mothers fed the diet containing 76 ng MeHg/g, presented a
      58% reduced activity in the open-field labyrinth, meaning that the maternal
      exposure to fish-containing food exerted an effect in utero that lasted several
      weeks after birth. Newborns were protected against Hg exposure by the placental
      barrier since in newborns from mothers fed the diet containing 76 ng MeHg/g of
      food, the concentrations of Hg in brain, kidney, liver and skeletal muscles
      represented 12, 3, 21 and 18% of those of their mother's tissues, respectively.
      These results suggest the existence, at least in rats, of a threshold level in
      terms of MeHg exposure above which the placental barrier collapses.

PMID- 30273634
TI  - Healthy play, better coping: The importance of play for the development of
      children in health and disease.
AB  - Play is of vital importance for the healthy development of children. From a
      developmental perspective, play offers ample physical, emotional, cognitive, and
      social benefits. It allows children and adolescents to develop motor skills,
      experiment with their (social) behavioural repertoire, simulate alternative
      scenarios, and address the various positive and negative consequences of their
      behaviour in a safe and engaging context. Children with a chronic or life
      threatening disease may face obstacles that negatively impact play and play
      development, possibly impeding developmental milestones, beyond the actual
      illness itself. Currently, there is limited understanding of the impact of (1)
      aberrant or suppressed play and (2) play-related interventions on the development
      of chronic diseased children. We argue that stimulating play behaviour enhances
      the adaptability of a child to a (chronic) stressful condition and promotes
      cognitive, social, emotional and psychomotor functioning, thereby strengthening
      the basis for their future health. Systematic play research will help to develop
      interventions for young patients, to better cope with the negative consequences
      of their illness and stimulate healthy development.

PMID- 30273635
TI  - Vesicular glutamate transporter isoforms: The essential players in the
      somatosensory systems.
AB  - In nervous system, glutamate transmission is crucial for centripetal conveyance
      and cortical perception of sensory signals of different modalities, which
      necessitates vesicular glutamate transporters 1-3 (VGLUT 1-3), the three
      homologous membrane-bound protein isoforms, to load glutamate into the
      presysnaptic vesicles. These VGLUTs, especially VGLUT1 and VGLUT2, selectively
      label and define functionally distinct neuronal subpopulations at each relay
      level of the neural hierarchies comprising spinal and trigeminal sensory systems.
      In this review, by scrutinizing each structure of the organism's fundamental
      hierarchies including dorsal root/trigeminal ganglia, spinal dorsal
      horn/trigeminal sensory nuclear complex, somatosensory thalamic nuclei and
      primary somatosensory cortex, we summarize and characterize in detail within each
      relay the neuronal clusters expressing distinct VGLUT protein/transcript
      isoforms, with respect to their regional distribution features (complementary
      distribution in some structures), axonal terminations/peripheral innervations and
      physiological functions. Equally important, the distribution pattern and
      characteristics of VGLUT1/VGLUT2 axon terminals within these structures are also
      epitomized. Finally, the correlation of a particular VGLUT isoform and its
      physiological role, disclosed thus far largely via studying the peripheral
      receptors, is generalized by referring to reports on global and conditioned VGLUT
      knockout mice. Also, researches on VGLUTs relating to future direction are
      tentatively proposed, such as unveiling the elusive differences between distinct
      VGLUTs in mechanism and/or pharmacokinetics at ionic/molecular level, and
      developing VGLUT-based pain killers.

PMID- 30273636
TI  - Fluid model of epithelial morphogenesis: Oscillations and structuring.
AB  - We have revised a mathematical model of epithelial morphogenesis by Belintsev et
      al. (1987) (BB model) taking into account the oscillatory nature of morphogenesis
      and stability analysis (Cherdantsev, 2014). Following the BB model in considering
      the feedback control of cell shape changes by mechanical forces, we modify it to
      represent epithelial surface movements observed in different types of Metazoan
      gastrulation. Basing on these observations, we argue that the epithelial surface
      movement is that of an incompressible fluid supplemented by a positive feedback
      between the movement and spreading of the surface flow. Dipole interactions
      between sources and sinks of surface energy provide a single mechanism both of
      short-ranged and long-ranged regulation of collective cell and surface movements
      whose basic variables are the space averaged epithelial surface curvature and
      lateral pressure within the epithelial surface flux negatively related to its
      velocity. The short-ranged activation means a movement of the surface up to the
      lateral pressure gradient under non-linear feedback control of the surface
      flexure. The break of this feedback with equalization of the surface curvature is
      sufficient for a self-restriction of the movement spreading. Owing to bistable
      interdependence between the lateral pressure and epithelial surface curvature, we
      get a generic oscillatory contour in which the same region oscillates being
      alternately a sink and source of the surface flow. The opposite phase
      oscillations of the lateral pressure and curvature allow for both directional
      propulsion of the surface through the same region and spatial differentiation
      based on parametric differences between the large-scaled regions that correspond
      to sources and sinks of the surface.

PMID- 30273637
TI  - Stress-generating tissue deformations in Xenopus embryos: Long-range gradients
      and local cell displacements.
AB  - BACKGROUND: Although the role of endogenous mechanical stresses in regulating
      morphogenetic movements and cell differentiation is now well established, many
      aspects of mechanical stress generation and transmission in developing embryos
      remain unclear and require quantitative studies. RESULTS: By measuring stress
      bearing linear deformations (caused by differences in cell movement rates) in the
      outer cell layer of blastula - early tail-bud Xenopus embryos, we revealed a set
      of long-term tension-generating gradients of cell movement rates, modulated by
      short-term cell-cell displacements much increasing the rates of local
      deformations. Experimental relaxation of tensions distorted the gradients but
      preserved and even enhanced local cell-cell displacements. During development, an
      incoherent mode of cell behavior, characterized by extensive cell-cell
      displacements and poorly correlated cell trajectories, was exchanged for a more
      coherent regime with the opposite characteristics. In particular, cell shifts
      became more synchronous and acquired a periodicity of several dozen minutes.
      CONCLUSIONS: Morphogenetic movements in Xenopus embryos are mediated by
      mechanically stressed dynamic structures of two different levels: extended
      gradients and short-term cell-cell displacements. As development proceeds, the
      latter component decreases and cell trajectories become more correlated. In
      particular, they acquire common periodicities, making morphogenesis more
      coherent.

PMID- 30273638
TI  - Cerebrospinal fluid collection in laboratory mice: Literature review and modified
      cisternal puncture method.
AB  - BACKGROUND: The composition of cerebrospinal fluid (CSF) is an invaluable
      parameter in better understanding of cellular and molecular processes within the
      mammalian brain. However, the collection of significant volumes of clean CSF can
      be technically challenging in studies with laboratory mice. Over the past five
      decades, several approaches have been developed to maximize the quantity and
      quality of CSF samples, either from live or euthanized animals. Due to the small
      amounts collected, samples from single mice were often pooled or diluted to meet
      volume requirements of automated counters and multiple assays. NEW METHOD: This
      paper reviews previous work on CSF collection in mice, thus providing
      methodological background for the current post-mortem procedure. This modified
      cisternal puncture method involves the use of a peristaltic pump for consistent
      and slow intracardiac perfusion, as well as a loupe headset with a custom-made
      glass pipette for piercing a single hole in the atlanto-occipital membrane during
      repeated CSF draws. Sample cleanness is verified by comparing the colour of the
      glass pipette and the bottom of centrifuged PCR vial against a white background.
      RESULTS: With three trained experimenters, the entire procedure (including
      anesthesia) takes ~11-13 min and often results in the collection of up to 40 MUl
      of clean CSF from males of different murine strains. Properly staggered
      collections allow processing of relatively large cohorts of mice per day.
      CONCLUSIONS: This modification of previously employed methods can be used in
      studies that require tightly-timed collections of larger volumes of undiluted,
      tissue-free CSF and/or individual data records.

PMID- 30273639
TI  - Impact of test protocols and material binding on the efficacy of antimicrobial
      wipes.
AB  - BACKGROUND: The use of effective cleaning/disinfectant products is important to
      control pathogens on healthcare surfaces. With the increasing number of wipe
      products available, there is a concern that combination of a formulation with the
      wrong material will decrease the efficacy of the product. This study aimed to use
      a range of efficacy test protocols to determine the efficacy of four formulations
      before and after binding to three commonly used wiping materials. METHODS: Two
      quaternary ammonium (QAC)-based products, one hydrogen-peroxide-based product and
      one neutral cleaner were combined with microfibre, cotton or non-woven materials
      and tested for efficacy against Pseudomonas aeruginosa and Staphylococcus aureus
      with two surface tests (ASTM E2197-17 and EN13697-15) and two 'product' tests
      (ASTM E2967-15 and EN16615-15). FINDINGS: Overall, the impact of using different
      materials on formulation efficacy was limited, except for an alkyl(C12
      16)dimethylbenzylammonium chloride-based product used at 0.5% v/v. The hydrogen
      peroxide product was the most efficacious regardless of the material used. The
      results from wipe test ASTM E2967-15 were consistent with those from the surface
      tests, but not with EN16615-15 which was far less stringent. CONCLUSIONS: The use
      of different wiping cloth materials may not impact severely on the efficacy of
      potent disinfectants, despite the absorption of different volumes of formulation
      by the materials. QAC-based formulations may be at higher risk when a low
      concentration is used. There were large differences in efficacy depending on the
      standard test performed, highlighting the need for more stringency in choosing
      the test to make a product claim on label.

PMID- 30273640
TI  - Why volume matters - Implications of applied volume of alcohol-based
      disinfectants for infection prevention.

PMID- 30273641
TI  - Gateway reflex: Local neuroimmune interactions that regulate blood vessels.
AB  - Neuroimmunology is a research field that intersects neuroscience and immunology,
      with the larger aim of gaining significant insights into the pathophysiology of
      chronic inflammatory diseases such as multiple sclerosis. Conventional studies in
      this field have so far mainly dealt with immune responses in the nervous system
      (i.e. neuroinflammation) or systemic immune regulation by the release of
      glucocorticoids. On the other hand, recently accumulating evidence has indicated
      bidirectional interactions between specific neural activations and local immune
      responses. Here we discuss one such local neuroimmune interaction, the gateway
      reflex. The gateway reflex represents a mechanism that translates specific neural
      stimulations into local inflammatory outcomes by changing the state of specific
      blood vessels to allow immune cells to extravasate, thus forming the gateway.
      Several types of gateway reflex have been identified, and each regulates distinct
      blood vessels to create gateways for immune cells that induce local inflammation.
      The gateway reflex represents a novel therapeutic strategy for neuroinflammation
      and is potentially applicable to other inflammatory diseases in peripheral
      organs.

PMID- 30273642
TI  - DNMT1 and Sp1 competitively regulate the expression of BACE1 in A2E-mediated
      photo-oxidative damage in RPE cells.
AB  - Numerous studies have focused on the deteriorate role of amyloid-beta (Abeta) on
      retina, implying the potential pathogenic mechanism underlying age-related
      macular degeneration (AMD). However, the mechanism underlying the Abeta
      deposition in AMD patients remains unknown. Beta-site amyloid precursor protein
      cleaving enzyme 1 (BACE1), rate-limiting enzyme for Abeta production, plays an
      important role in Abeta deposition in the brain. In the current study, we aimed
      to clarify the regulation mechanism of BACE1 and explore potential drug targets
      using a lipofuscinfluorophore A2E-mediated photo-oxidation model. In this model,
      Abeta1-40 and Abeta1-42 levels increased simultaneously with the enhanced BACE1
      expression. These changes were associated with the hypomethylation of specific
      loci within the BACE1 gene promoter and the decreased levels of DNA
      methyltransferase 1 (DNMT1). Furthermore, we noticed overlapping regions of
      differentially methylated CpG islands and specificity protein (Sp1) binding sites
      within the BACE1 promoter. We employed chromatin immunoprecipitation (ChIP) assay
      to verify that the decreased BACE1 promoter methylation by DNMT1 enabled
      increased binding between Sp1 and the BACE1 promoter, which further enhanced
      BACE1 transcription. The inhibition of Sp1 with mithramycin A (MTM) could down
      regulate the expression of BACE1 as well as alleviate the RPE barrier morphology
      and function impairment. Our results for the first time show the competitive
      regulation of BACE1 by transcription factor Sp1 and DNMT1 after photo-oxidation
      and confirm the potential novel protective role of MTM on RPE cells.

PMID- 30273643
TI  - Positional pseudo-alternating bundle-branch-block on implantable loop recorder
      electrogram.

PMID- 30273644
TI  - Subtractive proteomics and immunoinformatics revealed novel B-cell derived T-cell
      epitopes against Yersinia enterocolitica: An etiological agent of Yersiniosis.
AB  - Yersinia enterocolitica is the third most common cause of gastrointestinal
      manifestations in Europe. Statistically, every year the pathogen accounts for 640
      hospitalizations, 117,000 illnesses, and 35 deaths in the United States. The
      associated mortality rate of the pathogen is 50% and is virtually resistant to
      penicillin G, ampicillin and cephalotin. The development of new and effective
      therapeutic procedures is urgently needed to counter the multi-drug-resistant
      phenotypes imposed by the said pathogen. Based on subtractive reverse vaccinology
      and immunoinformatics approaches, we have successfully predicted novel antigenic
      peptide vaccine candidates against Y. enterocolitica. The pipeline revealed two
      isoforms of ompC family; meoA (ompC) and ompC2 as promising vaccine targets.
      Protein-protein interactions elaborated the involvement of target candidates in
      the major biological pathways of the pathogen. The predicted 9-mer B-cell derived
      T-cell epitope of proteins are found to be virulent, antigenic, non-allergic,
      surface exposed and conserved in all nine completely sequenced strains of the
      pathogen. Molecular docking predicts deep and stable binding of the epitopes in
      the binding pocket of the most predominant allele in human population-the
      DRB1*0101. These epitopes of target proteins could provide the foundation for the
      development of an epitope-driven vaccine against Y. enterocolitica.

PMID- 30273645
TI  - Late-onset cardiomyopathy among survivors of childhood lymphoma treated with
      anthracyclines: a systematic review.
AB  - Medical advances in pediatric oncology have led to increases in survival but the
      long-term adverse effects of treatment in childhood cancer survivors have not yet
      been examined in depth. In this systematic review, we aimed to study the
      prevalence and risk factors of late-onset cardiomyopathy (LOCM) among survivors
      of childhood lymphoma treated with anthracyclines. Following the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines we
      searched Pubmed/Medline, abstracted data and rated studies on quality regarding
      late-onset (>1 year following treatment) cardiotoxicity of anthracyclines in
      survivors of childhood lymphoma. Across 22 identified studies, the prevalence of
      anthracycline-induced LOCM among survivors of childhood lymphoma ranges from 0 to
      40%. Anthracycline dose, administration and dose of mediastinal radiation,
      patient's age and era of diagnosis and evaluation, follow-up duration as well as
      disease relapse have been reported as risk factors for LOCM, whereas
      administration of dexrazoxane seems to act protectively. There was significant
      between-study heterogeneity with regards to lymphoma subtypes, follow-up
      duration, definition of outcomes, and anthracycline-based treatment protocols.
      The rates of anthracycline-induced LOCM among survivors of childhood lymphoma are
      high and dependent on study design. Future studies should explore whether
      modifying risk factors and suggested supportive care could decrease its
      prevalence among childhood lymphoma survivors. Until then, lifelong follow-up of
      these patients aiming to determinate the earliest signs of cardiac dysfunction is
      the most important measure towards primordial prevention of LOCM.

PMID- 30273646
TI  - Partition of common atrioventricular valve in a patient with dextrocardia and
      univentricular circulation.

PMID- 30273647
TI  - The effect of preoperative anemia on patients undergoing cardiac surgery: a
      propensity-matched analysis.
AB  - OBJECTIVES: It is unknown if anemia in the absence of transfusions is an
      independent risk factor for adverse outcomes in cardiac surgery, and if
      correction to higher hemoglobin targets impacts these outcomes. METHODS: This is
      a retrospective review of 3,848 cardiac surgery patients. Propensity matching was
      completed using 41 covariates. Intraoperative Anemia Analysis (IAA) matched
      patients with or without anemia who did not receive intraoperative transfusions
      (n=392/group), while Intraoperative Transfusion Analysis (ITA) matched anemic
      patients treated conventionally with intraoperative transfusions to end CPB
      hemoglobin greater or less than 95 g/L (n=261/group). Outcomes of death, renal
      failure, and two composite outcomes were assessed using paired analysis
      techniques. Study composite 1 consisted of prolonged ventilation, renal failure,
      MI, stroke, or DSWI, while composite 2 was the TRICS-III composite. RESULTS: In
      the IAA, anemia was associated with mortality (p=0.034), stroke (p=0.021), renal
      failure (p=0.015) and a significant increase in the composite measure (control
      8.7% vs anemia 16.1%, p=0.002). These findings were unchanged in patients who did
      not receive any postoperative transfusions. The ITA showed no difference in
      mortality or the composite outcome between groups. There was a significant
      increase in low cardiac output in the lower threshold group (p=0.001). There were
      no differences in outcomes between those who did and did not receive
      postoperative transfusions (p>0.05). CONCLUSIONS: Preoperative anemia in the
      absence of transfusions is a risk factor for morbidity and mortality after
      cardiac surgery, and there is no evidence that transfusion to higher end CPB
      hemoglobin levels impacted this risk.

PMID- 30273648
TI  - 3D-Printing-Based Open Repair of Extensive Thoracoabdominal Aorta in Severe
      Scoliosis.

PMID- 30273649
TI  - A case of Histoplasma capsulatum variety capsulatum septic arthritis successfully
      treated with surgery, systemic antifungals, and local amphotericin cement beads.
AB  - Histoplasma capsulatum variety capsulatum (H. capsulatum) is a thermally
      dimorphic fungus that is endemic to the Mississippi River and Ohio River valley
      regions. Of the hundreds of thousands of patients exposed to this fungus, less
      than 1% develop a severe illness most commonly manifesting as pulmonary disease.
      Septic arthritis from hematogenous seeding with H. capsulatum or from direct
      inoculation has been reported only rarely in the literature. The first case of
      septic arthritis of the shoulder due to H. capsulatum occurring in an
      immunocompromised patient, treated successfully with irrigation and debridement,
      systemic antifungals, and local delivery of amphotericin B with cement beads, is
      reported here. Importantly, the addition of local amphotericin B delivery by
      cement beads to conventional treatment likely led to clinical cure in this
      patient.

PMID- 30273650
TI  - The biochemical characterization of a missense mutation m.8914C>T in ATP6 gene
      associated with mitochondrial encephalomyopathy.
AB  - Mutations in ATP6 gene are frequent causes of mitochondrial encephalomyopathies.
      ATP6 gene encodes one subunit of complexV. The present study described a missense
      mutation in ATP6 gene in a 8-year-old Chinese boy with mitochondrial
      encephalomyopathy. We identified one missense mutation in ATP6 gene (m.8914C>T)
      by mitochondrial DNA sequencing. This mutation altered the amino acid proline in
      serine, and alterative protein is predicted to be harmful. The mutation load in
      blood sample of patient is 59.49%. Activity of all mitochondrial complexes in
      blood are normal, however, the total function of mitochondrial oxidative
      phosphorylation were declined (including pathwayI, pathwayII and pathwayIV). The
      missense mutation (m.8914C>T) in ATP6 gene could result in abnormal function of
      complexV and is related with mitochondrial encephalomyopathy.

PMID- 30273651
TI  - TAK1 of black carp positively regulates IRF7-mediated antiviral signaling in
      innate immune activation.
AB  - Transforming growth factor beta-activated kinase 1 (TAK1) plays a vital role in
      IL-1-mediated NF-kappaB, JNK, and p38 activation in human and mammals. However,
      the function of TAK1 in teleost fish still remains largely unknown. To explore
      the role of TAK1 during the antiviral innate immune response of teleost fish,
      TAK1 of black carp (Mylopharyngodon piceus) was cloned and characterized in this
      paper. The open reading frame (ORF) of black carp TAK1 (bcTAK1) consists of 1626
      nucleotides and the predicted bcTAK1 protein contains 541 amino acids, which
      includes a N-terminal Serine/Threonine protein kinases (S/TKc) and a C-terminal
      coiled-coil region. bcTAK1 migrated around 75 kDa in immunoblotting assay and was
      identified as a cytosolic protein by immunofluorescence staining. bcTAK1
      transcription in Mylopharyngodon piceus kidney (MPK) cells varied in response to
      the stimulation of poly (I:C), LPS, grass carp reovirus (GCRV), and spring
      viremia of carp virus (SVCV). bcTAK1 showed deficient IFN-inducing ability in
      reporter assay and feeble antiviral activity against GCRV and SVCV in plaque
      assay. However, when co-expressed with bcIRF7 in EPC cells, bcTAK1 obviously
      enhanced bcIRF7-mediated IFN promoter induction in reporter assay. Accordingly,
      the data of plaque assay demonstrated that the antiviral activity of bcIRF7
      against both GCRV and SVCV was unregulated by bcTAK1. Thus, the data generated in
      this study support the conclusion that bcTAK1 up-regulates bcIRF7-mediated
      antiviral signaling during host innate immune activation, which is reported for
      the first time in vertebrates.

PMID- 30273652
TI  - Identification and characterization of a B-type mannose-binding lectin from Nile
      tilapia (Oreochromis niloticus) in response to bacterial infection.
AB  - Lectins are a group of carbohydrate-binding proteins, which play an important
      role in innate immune system against pathogen infection. In this study, a B-type
      mannose-binding lectin (OnBML) was identified from Nile tilapia (Oreochromis
      niloticus), and characterized at expression patterns against bacterial infection
      and capability to promote phagocytosis by macrophages. The open reading frame of
      OnBML is 354 bp of nucleotide sequence encoding polypeptides of 117 amino acids.
      The deduced protein is highly homologous to other teleost BMLs, containing two
      repeats of the conserved mannose-binding motif QXDXNXVXY. Expression of OnBML was
      widely exhibited in all examined tissues, with the most abundance in spleen and
      following gill, peripheral blood, and head kidney. The OnBML expressions were
      significantly up-regulated following two major bacterial infections including a
      Gram-positive bacterium (Streptococcus agalactiae) and a Gram-negative bacterium
      (Aeromonas hydrophila) in vivo and in vitro. Recombinant OnBML protein possessed
      capacities of mannose-binding and calcium-dependent agglutination to S.
      agalactiae and A. hydrophila, and promoted the phagocytosis by macrophages. Taken
      together, the present study indicated that OnBML is likely to get involved in
      host defense against bacterial infection in Nile tilapia.

PMID- 30273653
TI  - Perineuronal nets in brain physiology and disease.
AB  - Perineuronal nets (PNNs) in the brain are condensed glycosaminoglycan-rich
      extracellular matrix structures with heterogeneous composition yet specific
      organization. They typically assemble around a subset of fast-spiking
      interneurons that are implicated in learning and memory. Owing to their unique
      structural organization, PNNs have neuroprotective capacities but also
      participate in signal transduction and in controlling neuronal activity and
      plasticity. In this review, we define PNN structure in detail and describe its
      various biochemical and physiological functions. We further discuss the role of
      PNNs in brain disorders such as schizophrenia, bipolar disorder, Alzheimer
      disease and addictions. Lastly, we describe therapeutic approaches that target
      PNNs to alter brain physiology and counter brain dysfunction.

PMID- 30273654
TI  - Fibroblast growth factor 18 exerts anti-osteoarthritic effects through PI3K-AKT
      signaling and mitochondrial fusion and fission.
AB  - Osteoarthritis (OA) is a degenerative disease characterized by progressive loss
      of cartilage, osteophyte formation and subchondral bone sclerosis. Although some
      animal experiments have reported that fibroblast growth factor 18 (FGF18)
      attenuates cartilage degradation, the effect of FGF18 on chondrocytes and its
      underlying mechanism at the cellular level remain largely unknown. In this study,
      we found that an intra-articular injection of FGF18 attenuates cartilage
      degradation, increases Collagen II deposition and suppresses matrix
      metallopeptidase 13 (MMP13) expression in rat post-traumatic osteoarthritis
      (PTOA). At the cellular level, FGF18 promotes chondrocyte proliferation through
      PI3K-AKT signaling and migration through PI3K signaling. We found that FGF18
      attenuates IL-1beta-induced apoptosis, restores mitochondrial function and
      reduces Reactive Oxygen Species (ROS) production through PI3K-AKT signaling.
      Moreover, the mitochondrial fusion and fission of chondrocytes were enhanced by a
      short duration of treatment (within 24 h) of IL-1beta and suppressed by prolonged
      treatment (48 h). FGF18 significantly enhances the mitochondrial fusion and
      fission, restoring mitochondrial function and morphology, and reduces ROS
      production. We also found that the FGFR1/FGFR3 ratio, which might contribute to
      the progression of osteoarthritis, was upregulated by IL-1beta and downregulated
      by FGF18. To the best of our knowledge, our data demonstrated the anti
      osteoarthritic effect of FGF18 at the cellular level for the first time and
      suggested that PI3K-AKT signaling and mitochondrial fusion and fission might play
      critical roles during the process. Our study proved that FGF18 might be a
      promising drug for the treatment of early stage osteoarthritis and is worth
      further study.

PMID- 30273655
TI  - Metabolism and epigenetics of pancreatic cancer stem cells.
AB  - Pancreatic Cancer (PDA) is an aggressive malignancy characterized by early spread
      and a high mortality. Current studies suggest that a subpopulation of cells exist
      within tumors, cancer stem cell (CSC), which are capable of self-renewal and give
      rise to unique progeny which form the major neoplastic cellular component of
      tumors. While CSCs constitute a small cellular subpopulation within the tumor,
      their resistance to chemotherapy and radiation make them an important therapeutic
      target for eradication. Along with distinctive phenotypic properties, CSCs
      possess a unique metabolic plasticity allowing them to rapidly respond and adapt
      to environmental changes. These cells and their progeny also display a
      significantly altered epigenetic state with distinctive patterns of DNA
      methylation. Several mechanisms of cross-talk between epigenetic and metabolic
      pathways in PDA exist which ultimately contribute to the observed cellular
      plasticity and enhanced tumorigenesis. In this review we discuss various examples
      of this metabolic-epigenetic interplay and how it may constitute a new avenue for
      therapy specifically targeting CSCs in PDA.

PMID- 30273656
TI  - Parallels between artificial reprogramming and the biogenesis of cancer stem
      cells: Involvement of lncRNAs.
AB  - Cellular identity is established and maintained by the interplay of cell type
      specific transcription factors and epigenetic regulation of the genome. During
      development in vivo and differentiation in vitro, transitions from one cell type
      to the next are triggered by cell signaling events culminating in modifications
      of chromatin that render genes accessible or inaccessible to the transcriptional
      apparatus. In recent years it has become apparent that cellular identity is
      plastic, and technological reprogramming methods such as somatic cell nuclear
      transfer and induced pluripotency can yield reprogrammed cells that have been
      restored to a state of developmental potency. Long noncoding RNAs (lncRNAs) are
      untranslated functional RNA molecules that are intimately involved in the
      regulation of the chromatin of protein-coding genes. In fact, recent evidence
      shows that there are more lncRNA species in the cell than mRNA species and that
      most protein-coding genes are likely to be under epigenetic regulation mediated
      by lncRNAs. This review examines lncRNA function in reprogrammed pluripotent
      cells and cancer stem cells. Because cancer stem cells arise from normal cells,
      their biogenesis can be viewed as a reprogramming process that occurs in vivo,
      and parallels between artificial reprogramming and cancer stem cell biogenesis
      are discussed.

PMID- 30273657
TI  - DNP NMR of biomolecular assemblies.
AB  - Dynamic Nuclear Polarization (DNP) is an effective approach to alleviate the
      inherently low sensitivity of solid-state NMR (ssNMR) under magic angle spinning
      (MAS) towards large-sized multi-domain complexes and assemblies. DNP relies on a
      polarization transfer at cryogenic temperatures from unpaired electrons to
      adjacent nuclei upon continuous microwave irradiation. This is usually made
      possible via the addition in the sample of a polarizing agent. The first
      pioneering experiments on biomolecular assemblies were reported in the early
      2000s on bacteriophages and membrane proteins. Since then, DNP has experienced
      tremendous advances, with the development of extremely efficient polarizing
      agents or with the introduction of new microwaves sources, suitable for NMR
      experiments at very high magnetic fields (currently up to 900 MHz). After a brief
      introduction, several experimental aspects of DNP enhanced NMR spectroscopy
      applied to biomolecular assemblies are discussed. Recent demonstration
      experiments of the method on viral capsids, the type III and IV bacterial
      secretion systems, ribosome and membrane proteins are then described.

PMID- 30273658
TI  - Map challenge: Analysis using a pair comparison method based on Fourier shell
      correlation.
AB  - This document presents the analysis performed over the Map Challenge dataset
      using a new algorithm which we refer to as Pair Comparison Method. The new
      algorithm, which is described in detail in the text, is able to sort
      reconstructions based on a figure of merit and assigns a level of significance to
      the sorting. That is, it shows how likely the sorting is due to chance or if it
      reflects real differences.

PMID- 30273659
TI  - Cochrane systematic reviews: contributions and perspectives.

PMID- 30273660
TI  - Myelitis and tenosynovitis attributed to toxocariasis.

PMID- 30273661
TI  - Evaluating the clinical importance of bacterial degradation of therapeutic agents
      in the lower intestine of adults using adult fecal material.
AB  - PURPOSE: Optimize adult fecal material composition for evaluating the clinical
      importance of bacterial degradation of therapeutic agents in the lower intestine
      (distal small intestine, D-SI and proximal colon, P-COL). Evaluate the usefulness
      of optimized fecal material in the evaluation of bacterial degradation of five
      model highly permeable drugs: two nitroreductase substrates (nitrendipine and
      nimodipine), three drugs for which published data indicate no impact of bacterial
      degradation on in vivo performance (levodopa, budesonide and rivaroxaban) and one
      prodrug (sulfasalazine, an azoreductase substrate) from which a locally acting on
      the mucosa of the lower intestine drug is derived (mesalamine). METHODS: 30 min
      and 95 min were used as point estimates of maximum bacterial degradation half
      lives for bacterial degradation in D-SI or in P-COL, respectively, to be
      clinically important, i.e. for at least 20% reduction in absorption from D-SI or
      P-COL to occur. Optimization of fecal material was based on recently reported
      degradation profiles of metronidazole (a nitroreductase substrate) and olsalazine
      (an azoreductase substrate) in the lower intestine of healthy adults which are
      clinically important. Model compounds were tested in optimized fecal materials
      and data were evaluated vs. existing in vivo data in adults. RESULTS: Simulated
      ileal bacteria (SIB) consisted of 5.5% (w/v) stools in normal saline and
      simulated colonic bacteria (SCoB) consisted of 8.3% (w/v) stools in normal
      saline. For all model compounds, data in SIB and SCoB were in line with available
      information in adults. [Degradation half-life in SIB/Degradation half-life in
      SCoB] ~ [Stool content in SCoB/Stool content in SIB] ~ 1.5, i.e. bacterial
      degradation in SIB could be predicted from bacterial degradation in SCoB.
      CONCLUSION: Data in SCoB only are useful for evaluating whether bacterial
      degradation in P-COL and in D-SI is likely to be clinically important for orally
      administered, highly permeable drugs or prodrugs which act locally after
      bacterial degradation. The usefulness of this approach in cases where enzymes
      other than nitroreductases or azoreductases are involved requires further
      confirmation.

PMID- 30273663
TI  - Pluchea lanceolata protects hippocampal neurons from endothelin-1 induced
      ischemic injury to ameliorate cognitive deficits.
AB  - Ischemic brain injury is one of the leading causes of death and disability, where
      lack of disease modifying treatment strategies make us rely on symptomatic
      relief. Treatment principles from traditional systems of medicine may fill this
      gap and its validation in modern medicine perspective is important to bring them
      to mainstream. Here, we evaluated the neuroprotective efficacy of Ayurvedic
      medicinal herb Pluchea lanceolata in treating ischemic hippocampal injury. Focal
      hippocampal ischemia was modeled in Wistar rats through stereotaxic
      intrahippocampal injection of endothelin-1 (ET-1). Post-surgery, hydroalcoholic
      extract of the rhizome of Pluchea lanceolata (HAPL) was administered orally, once
      in a day for 14 consecutive days to ischemic rats. There were two treatment
      groups based on the HAPL dosage; HAPL200 (200 mg/kg body weight) and HAPL400 (400
      mg/kg body weight). Comparisons were made with the ET-1 ischemic rats which
      received only the vehicle, and the normal surgical control. Ischemic hippocampal
      injury led to severe cognitive deficits as evaluated by Morris water maze and
      open field test, along with locomotory dysfunction noted in actophotometer test.
      HAPL treatment significantly attenuated these behavioural deficits in a dose
      dependent manner. Loss of pyramidal cells and degenerative phenotype of shrunken
      hyperdensed soma with pyknotic nuclei in CA1 and CA3 hippocampal neurons in
      ischemia were reversed after HAPL treatment. We provide first evidence for loss
      of dendritic architecture in ET-1 induced focal ischemic hippocampal injury using
      Golgi impregnation, where HAPL could salvage the dendritic branching and
      intersections. Intriguingly, it enhanced the dentritic arborization beyond what
      is noted in normal rats. Ability of HAPL to reverse oxidative stress, especially
      through maintaining glutathione peroxidase levels and lipid peroxidation in
      ischemic condition evidences that it may exert neuroprotection through its
      antioxidant properties. Thus, Pluchea lanceolata and its constituents provide
      potential alternative/adjuvant treatment strategy for ischemic hippocampal
      stroke.

PMID- 30273664
TI  - Dual role of laminin-511 in regulating melanocyte migration and differentiation.
AB  - Laminins are the major basement membrane (BM) components and are heterotrimers
      composed of an alpha, a beta and a gamma chain. In skin, laminins are present in
      basement membranes surrounding vascular structures, nerves, adipose tissue and in
      the specialized junctional BM between the epidermis and dermis. The main laminin
      isoforms in the dermo-epidermal BM are laminin-332, laminin-511 and laminin-211,
      the latter being restricted to hair follicles (HFs). The laminin gamma1 chain is
      the most abundant gamma chain; its global ablation in mice leads to early
      embryonic lethality at E5.5. To elucidate the cellular function of the gamma1
      chain in skin, we generated mice with keratinocyte-specific deletion of this
      chain (Lamc1EKO) by using the keratin (K)14-Cre/loxP system. These mice showed
      delayed coat pigmentation despite normal melanocyte counts in the skin. However,
      levels of differentiation-specific melanocyte enzymes TRP-1, TRP-2 and tyrosinase
      were reduced in Lamc1EKO mice, and melanocytes failed to migrate to their
      differentiation niche in HFs and accumulated in the IFE. These results suggested
      that the pigmentation defect results from impaired melanocyte migration. The
      impaired migratory capacity of melanocytes is due to the altered composition of
      laminins in the BM of Lamc1EKO mice: Loss of keratinocyte-derived pro-migratory
      laminin-511 is not compensated by ectopically deposited fibroblast-derived
      laminin-211. Furthermore, contact of melanocytes with recombinant laminin-511,
      but not with laminin-211, induces the expression of the chemokine receptor CXCR4
      on melanocytes, needed for SDF-1 (stromal cell-derived factor-1)-mediated
      migration into HFs. We here demonstrate that laminin-511 controls the
      differentiation of melanocytes by regulating their migration from the epidermis
      into HFs and by activating CXCR4 expression on melanocytes required for their
      recruitment into HFs in an SDF-1-dependent manner.

PMID- 30273662
TI  - The FTO rs9939609 "A" allele is associated with impaired fasting glucose and
      insulin resistance in Emirati population.
AB  - BACKGROUND: Fat mass and obesity-associated protein gene variants have shown
      diverse influence on body weight and metabolism across different populations.
      Overweight, obesity and metabolic syndrome are multifactorial major health
      problems in the UAE and worldwide. Insulin resistance represents the link between
      overweight and development of metabolic syndrome and type 2 diabetes mellitus. We
      investigated two (FTO) variants in Emirati population, in relation to insulin
      resistance and different parameters of metabolic syndrome. METHODS: We recruited
      259 Emiratis through the UAE National Diabetes and Lifestyle Project. Ethical
      approval was obtained. Besides basic data collection, venous blood samples were
      collected. Fasting blood glucose, Lipid profile, and insulin levels were
      measured. Genotyping for (FTO) rs9939609 (A>T) and rs9930506 (G>A) were performed
      using real time-PCR. Insulin resistance were identified using HOMA2-IR
      calculation; with a cut-off point of 1.4 for female and 1.18 for male subjects.
      RESULTS: The study included 259 Emiratis (age range 30-53 years, mean 41.76
      years, 54.4% females), 24.5% are diabetic and 30.8% are hypertensive, with body
      mass index of 28.4 +/- 5.9 and 28.7 +/- 5.7 kg/m2 in female and male subjects,
      respectively. Homozygous A of rs9939609 showed significantly higher fasting
      glucose compared to other genotypes (p = 0.04) with a trend of higher insulin
      level and HOMA-2IR. The A/A diabetic patients (n = 13) showed significantly
      higher insulin levels compared to other genotypes. G allele of rs9930506 showed a
      trend of higher fasting glucose and HOMA-2IR, but lower insulin level and HbA1c.
      No association of genotypes was detected with other components of metabolic
      syndrome. CONCLUSION: There is an association of FTO rs9939609 A/A genotype and
      impaired fasting glucose and insulin resistance. Homozygous A genotype diabetic
      patients may be more vulnerable to blood glucose fluctuation. Focused genotyping
      can help the health care providers to identify high risk groups of both normal
      population and diabetic patients to intervene accordingly.

PMID- 30273665
TI  - Orodispersible films based on blends of trehalose and pullulan for protein
      delivery.
AB  - During the last decades the number of therapeutic proteins increased tremendously
      on the pharmaceutical market. However, due to their often poor stability and
      limitations of the administration route, the application of therapeutic proteins
      is a major challenge. The oral mucosa has been suggested as a possible route for
      protein delivery. In this study, we prepared protein loaded orodispersible films
      (ODFs), based on blends of trehalose/pullulan by air- and freeze-drying. These
      two carbohydrates were selected based on the excellent protein stabilizing
      capacity of trehalose and film-forming ability of pullulan. ODFs were loaded with
      three model proteins. Ovalbumin was used to study the effect of protein
      incorporation on the mechanical properties, disintegration time, uniformity of
      weight and thickness of the ODFs. Lysozyme and beta-galactosidase were used to
      evaluate protein stability. Ovalbumin loading did not significantly influence the
      mechanical properties of freeze-dried ODFs, while incorporation of ovalbumin in
      air-dried ODFs led to a substantial reduction in tensile strength. The
      trehalose/pullulan ratio had no impact on the stability of lysozyme, while the
      stability of beta-galactosidase increased with increasing trehalose/pullulan
      ratios. Furthermore, freeze-drying appeared to be favorable over air-drying for
      process stability while the reverse was found for storage stability. In
      conclusion, trehalose/pullulan-based ODFs are from a technical point promising
      for possible protein delivery via the oral cavity.

PMID- 30273666
TI  - Sulfur dioxide attenuates sepsis-induced cardiac dysfunction via inhibition of
      NLRP3 inflammasome activation in rats.
AB  - OBJECTIVE: Sulfur dioxide (SO2) plays an important role in maintaining
      homeostasis of cardiovascular system. This study was aimed to investigate
      cardioprotective effects of SO2 on in the rat and the underlying mechanism.
      METHODS AND RESULTS: Sepsis model induced by cecal ligation and puncture (CLP) in
      rats were used. SO2 donor (NaHSO3/Na2SO3, 1:3 M/M) was administered
      intraperitoneally at a dose of 85 mg/kg. Primary neonatal rat cardiac ventricular
      myocytes (NRCMs) were stimulated with LPS (1 mg/mL) in presence or absence of
      different concentrations of SO2 (10, 50 and 100 MUmol/L). SO2 donor could restore
      the decreased levels of SO2 in plasma and heart of septic rats. SO2 exhibited
      dramatic improvement in cardiac functions. At 24 h after CLP, SO2 treatments
      decreased the number of TUNEL-positive cells, Bax/Bcl-2 ratio and activity of
      caspase-3. Moreover CLP-induced inflammatory response was also relieved by SO2.
      In NRCMs, SO2 could suppress the LPS-induced myocardial injury, leading to an
      increase in cell viability, a decrease in LDH and apoptotic rate. Western blot
      showed that the expression of TLR4, NLRP3, and Caspase-1 were obviously increased
      in myocardial tissue of CLP group or in NRCMs of LPS group, while SO2
      significantly inhibited the CLP-induced or LPS-induced TLR4, NLRP3, and Caspase-1
      expression. CONCLUSION: SO2 attenuated sepsis-induced cardiac dysfunction likely
      in association with the inhibiting inflammation via TLR4/NLRP3 signaling pathway.

PMID- 30273667
TI  - War, migration and Cystic Echinococcosis.

PMID- 30273668
TI  - Antibacterial and antivirulence activities of auranofin against Clostridium
      difficile.
AB  - Clostridium difficile is a deadly, opportunistic bacterial pathogen. In the last
      two decades, C. difficile infections (CDIs) have become a national concern
      because of the emergence of hypervirulent mutants with increased capability to
      produce toxins and spores. This has resulted in an increased number of infections
      and deaths associated with CDI. The scarcity of anticlostridial drugs has led to
      unsatisfactory cure rates, elevated recurrence rates and permitted enhanced
      colonization with other drug-resistant pathogens (such as vancomycin-resistant
      enterococci) in afflicted patients. Therefore, both patients and physicians are
      facing an urgent need for more effective therapies to treat CDI. In an effort to
      find new anticlostridial drugs, we investigated auranofin, an FDA-approved oral
      antirheumatic drug that has recently been found to possess antibacterial
      activity. Auranofin exhibited potent activity against C. difficile isolates,
      inhibiting growth at a concentration of 1 ug/mL against 50% of all tested
      isolates. Auranofin inhibited both toxin production and spore formation, a
      property lacking in both vancomycin and metronidazole (the primary agents used to
      treat CDI). Auranofin had a direct protective activity against C. difficile toxin
      mediated inflammation and inhibited the growth of vancomycin-resistant
      enterococci. Auranofin is a promising candidate that warrants further
      investigation as a treatment option for C. difficile infections.

PMID- 30273670
TI  - The salivary hyaluronidase and apyrase of the sand fly Sergentomyia schwetzi
      (Diptera, Psychodidae).
AB  - Current knowledge of sand fly salivary components has been based solely on
      Lutzomyia and Phlebotomus species which feed mainly on mammals; their
      hyaluronidases and apyrases were demonstrated to significantly affect blood meal
      intake and transmission of vector-borne pathogens. Members of the third sand fly
      genus Sergentomyia preferentially feed on reptiles but some of them are
      considered as Leishmania and arboviruses vectors; however, nothing is known about
      their salivary components that might be relevant for pathogens transmission.
      Here, marked hyaluronidase and apyrase activities were demonstrated in the saliva
      of a Sergentomyia schwetzi colony maintained on geckos. Hyaluronidase of S.
      schwetzi cleaved hyaluronan as the prominent substrate, and was active over a
      broad pH range from 4.0 to 8.0, with a sharp peak at pH 5.0. SDS PAGE zymography
      demonstrated the monomeric character of the enzyme, which remained active in
      reducing conditions. The apparent molecular weight of 43 kDa was substantially
      lower than in any sand fly species tested so far and may indicate relatively low
      grade of the glycosylation of the enzyme. The apyrase of S. schwetzi was typical
      strictly Ca2+ dependent Cimex-family apyrase. It was active over a pH range from
      6.5 to 9.0, with a peak of activity at pH 8.5, and had an ATPase/ADPase ratio of
      0.9. The apyrase activity increased during the first 3 days post-emergence, then
      reached a plateau and remained relatively constant until day 8. In comparison
      with a majority of Phlebotomus and Lutzomyia species tested to date, both the
      hyaluronidase and apyrase activities of S. schwetzi were relatively low, which
      may reflect an adaptation of this sand fly to blood feeding on non-mammalian
      hosts.

PMID- 30273669
TI  - Chemical chaperone-conjugated exendin-4 as a cytoprotective agent for pancreatic
      beta-cells.
AB  - Endoplasmic reticulum stress has been considered a major cause of pancreatic beta
      cell dysfunction and apoptosis leading to diabetes. Glucagon-like peptide-1
      receptor activation and chemical chaperones have been known to reduce endoplasmic
      reticulum stress and improve beta-cell function and survival. The purpose of this
      study was to prepare and evaluate the chemical chaperone tauroursodeoxycholic
      acid-conjugated exendin-4 as a protective agent for pancreatic beta-cells. Mono
      tauroursodeoxycholic acid-Lys27-exendin-4 conjugate (TUM1-Ex4) showed better
      receptor binding affinity than other conjugates with strong in vitro
      insulinotropic activity in rat pancreatic beta-cells and in vivo hypoglycemic
      activity in type 2 diabetic db/db mice. In INS-1 cells under endoplasmic
      reticulum stress induced by thapsigargin, TUM1-Ex4 promoted cell survival in a
      dose-dependent manner. In western blot analysis, TUM1-Ex4 reduced the expression
      of the endoplasmic reticulum stress marker GRP78 and phosphorylation of the
      translation initiation factor eIF2alpha. These results reveal that TUM1-Ex4
      accelerates translational recovery and contributes to beta-cell protection and
      survival. The present study indicates that the chemical chaperone-coupled
      glucagon-like peptide-1 receptor agonist is a feasible therapeutic strategy to
      enhance beta-cell function and survival.

PMID- 30273671
TI  - Co-infection of Clostridioides (Clostridium) difficile GMU1 and Bacillus cereus
      GMU2 in one patient in Guizhou, China.
AB  - Clostridioides (Clostridium) difficile and Bacillus cereus infections are
      frequently reported in human individually. However, co-infection of both
      pathogens in human is extremely rare. In the present study, we reported a case of
      human enteric disease caused by co-infection of C. difficile and B. cereus in
      Guizhou, China. The 16S rDNA sequencing result showed that C. difficile GMU1 and
      B. cereus GMU2 were most related to C. difficile ATCC 9689 and B. cereus ATCC
      14579. The toxin genotype of C. difficile GMU1 and B. cereus GMU2 were
      tcdA+tcdB+tcdC+ and bceT+nheA+nheB+nheC+, respectively. Cytotoxicity assay
      demonstrated that C. difficile GMU1 produced significantly higher toxin B compare
      to C. difficile 630 stain. In contrast, B. cereus GMU2 has comparable NheA toxin
      productivity compare to previous report. The antimicrobial susceptibility test
      showed that the combination of ampicillin and vancomycin was most efficient to
      inhibit both C. difficile GMU1 and B. cereus GMU2.

PMID- 30273672
TI  - Cathelicidin-WA attenuates LPS-induced inflammation and redox imbalance through
      activation of AMPK signaling.
AB  - Dysregulated activation of inflammation is associated with the development and
      progression of many diseases. Generation of reactive oxygen species (ROS) has
      been shown to promote an inflammatory response. Cathelicidin peptides not only
      defend against the invasion of various microbes but also play an important role
      in regulating immune responses. The objective of this study was to investigate
      the effects and mechanisms of Cathelicidin-WA (CWA) on the inflammatory response
      and oxidative stress in macrophages. Our results showed that CWA efficiently
      attenuated lipopolysaccharide (LPS)-stimulated inflammation and oxidative stress
      both in vivo and in vitro. Mechanistically, we found that CWA significantly
      reduced the LPS-induced nuclear translocation of NF-kappaB, thus decreasing the
      production of the pro-inflammatory cytokines TNF-alpha and IL-6 in macrophages.
      On the other hand, CWA markedly promoted the nuclear translocation of Nrf2 via
      the AKT pathway and p38 signaling. This resulted in increased expression of the
      anti-oxidative genes NQO-1 and HO-1 and alleviated oxidative stress in LPS
      stimulated macrophages. Interestingly, the effects of CWA were diminished when
      AMPK was knocked down. Consistently, we noticed that CWA failed to ameliorate the
      LPS-induced inflammatory response and oxidative stress in AMPK knockout mice.
      Furthermore, we discovered that LKB1 was essential for AMPK activation by CWA.
      These data demonstrated for the first time that CWA attenuated LPS-stimulated
      inflammation and redox imbalance through regulating LKB1-AMPK signaling. Such
      knowledge provides new insights into the mechanisms through which Cathelicidin
      peptides modulate immune responses.

PMID- 30273673
TI  - Ask the Authors.

PMID- 30273674
TI  - Ask the Authors.

PMID- 30273675
TI  - Optimal human iPS cell culture method for efficient hepatic differentiation.
AB  - Hepatocyte-like cells differentiated from human iPS cells are expected to be
      utilized in pharmaceutical research and regenerative medicine. Recently, various
      culture methods for human iPS cell maintenance have been developed. However, it
      is not well known whether human iPS cell maintenance method affects hepatic
      differentiation potency. In this study, we cultured human iPS cells using four
      maintenance methods: ReproStem medium with feeder cells (mouse embryonic
      fibroblasts), AK02N medium with iMatrix-511 (E8 fragments of laminin511),
      Essential 8 medium with Vitronectin N (N-terminal domain of vitronectin), TeSR-E8
      medium with Vitronectin XF (xeno-free vitronectin). Then, these human iPS cells
      were differentiated into the hepatocyte-like cells. Interestingly, the gene
      expression levels of definitive endoderm markers in the definitive endoderm cells
      generated from human iPS cells cultured with ReproStem or TeSR-E8 medium were
      higher than those in other groups. The gene expression level of foregut marker,
      HHEX, in the definitive endoderm cells generated from human iPS cells cultured
      with ReproStem medium was higher than that in other groups. Consistently, the
      expression levels of hepatocyte markers, albumin and urea secretion capacity, and
      CYP3A4 activity in the hepatocyte-like cells generated from human iPS cells
      cultured with ReproStem medium were higher than those in the other groups. Our
      data indicated that the most suitable human iPS cell maintenance method for
      efficient hepatic differentiation was the on-feeder method which uses mouse
      embryonic fibroblasts, but not feeder-free methods. In conclusion, human iPS cell
      maintenance method largely affects hepatic differentiation potency.

PMID- 30273676
TI  - Significance of urinary 11-dehydro-thromboxane B2 in age-related diseases: Focus
      on atherothrombosis.
AB  - Platelet activation plays a key role in atherogenesis and atherothrombosis.
      Biochemical evidence of increased platelet activation in vivo can be reliably
      obtained through non-invasive measurement of thromboxane metabolite (TXM)
      excretion. Persistent biosynthesis of TXA2 has been associated with several
      ageing-related diseases, including acute and chronic cardio-cerebrovascular
      diseases and cardiovascular risk factors, such as cigarette smoking, type 1 and
      type 2 diabetes mellitus, obesity, hypercholesterolemia, hyperhomocysteinemia,
      hypertension, chronic kidney disease, chronic inflammatory diseases. Given the
      systemic nature of TX excretion, involving predominantly platelet but also
      extraplatelet sources, urinary TXM may reflect either platelet cyclooxygenase-1
      (COX-1)-dependent TX generation or COX-2-dependent biosynthesis by inflammatory
      cells and/or platelets, or a combination of the two, especially in clinical
      settings characterized by low-grade inflammation or enhanced platelet turnover.
      Although urinary 11-dehydro-TXB2 levels are largely suppressed with low-dose
      aspirin, incomplete TXM suppression by aspirin predicts the future risk of
      vascular events and death in high-risk patients and may identify individuals who
      might benefit from treatments that more effectively block in vivo TX production
      or activity. Several disease-modifying agents, including lifestyle intervention,
      antidiabetic drugs and antiplatelet agents besides aspirin have been shown to
      reduce TX biosynthesis. Taken together, these aspects may contribute to the
      development of promising mechanism-based therapeutic strategies to reduce the
      progression of atherothrombosis. We intended to critically review current
      knowledge on both the pathophysiological significance of urinary TXM excretion in
      clinical settings related to ageing and atherothrombosis, as well as its
      prognostic value as a biomarker of vascular events.

PMID- 30273677
TI  - Exploring the Diagnosis and Profile of Cannabis Allergy.
AB  - BACKGROUND: Cannabis allergy (CA) has mainly been attributed to Can s 3, the
      nonspecific lipid transfer protein (nsLTP) of Cannabis sativa. Nevertheless,
      standardized diagnostic tests are lacking and research on CA is scarce.
      OBJECTIVE: To explore the performance of 5 cannabis diagnostic tests and the
      phenotypic profile of CA. METHODS: A total of 120 patients with CA were included
      and stratified according to the nature of their cannabis-related symptoms; 62
      healthy and 189 atopic controls were included. Specific IgE (sIgE) hemp, sIgE and
      basophil activation test (BAT) with a recombinant Can s 3 protein from Cannabis
      sativa (rCan s 3), BAT with a crude cannabis extract, and a skin prick test (SPT)
      with an nCan s 3-rich cannabis extract were performed. Clinical information was
      based on patient history and a standardized questionnaire. RESULTS: First, up to
      72% of CA reporting likely-anaphylaxis (CA-A) are Can s 3 sensitized. Actually,
      the Can s 3-based diagnostic tests show the best combination of positive and
      negative predictive values, 80% and 60%, respectively. sIgE hemp displays 82%
      sensitivity but only 32% specificity. Secondly, Can s 3+CA reported significantly
      more cofactor-mediated reactions and displayed significantly more sensitizations
      to other nsLTPs than Can s 3-CA. Finally, the highest prevalence of systemic
      reactions to plant-derived foods was seen in CA-A, namely 72%. CONCLUSIONS: The
      most effective and practical tests to confirm CA are the SPT with an nCan s 3
      rich extract and the sIgE rCan s 3. Can s 3 sensitization entails a risk of
      systemic reactions to plant-derived foods and cofactor-mediated reactions.
      However, as Can s 3 sensitization is not absolute, other cannabis allergens
      probably play a role.

PMID- 30273678
TI  - Performance of MRI for the detection of anterior pelvic endometriotic lesions.
AB  - OBJECTIVE: To study the performance of MRI for the detection of anterior pelvic
      endometriotic lesions. MATERIALS AND METHODS: We carried out a retrospective,
      single site, case-controlled study of patients who underwent surgery for
      endometriosis between March 2005 and December 2013. Laparoscopy was used to
      obtain the reference diagnosis of the endometriotic lesions. We age-matched
      patients with anterior endometriosis with those with isolated posterior
      endometriosis for reference. All of the pre-therapeutic MRI data were anonymized
      and blindly reread by two radiologists (junior and senior) twice. They assessed
      the overall presence of anterior lesions, those of the inter-vesicouterine space,
      the detrusor, the uterus, and posterior lesions. For each site, we calculated the
      sensitivity (Se) and specificity (Sp) for each reading compared to the reference,
      as well as the inter- and intra-operator variability using the Kappa coefficient
      (K) with its 95% confidence interval (95% CI). RESULTS: During the study period,
      256 patients underwent surgery for endometriosis: 22 presented with anterior
      endometriosis at surgery, and had had pre-preoperative imagery. We included 22
      controls who had an isolated posterior lesion. For the overall detection of
      anterior lesions, the two radiologists had an identical Se of 77.3% (95% CI; 54.6
      92.2). The Sp was 100% (95% CI; 82.4-100) for the junior, and 89.5% (95% CI; 66.9
      98.7) for the senior radiologist. The area under the ROC curve was 0.89 (95% CI;
      0.80-0.98) for the junior and 0.81 (95% CI; 0.68-0.93) for the senior
      radiologist. The intra-operator variability was low with almost perfect
      reproducibility for the overall detection of anterior lesions; k=0.90 (95% CI;
      0.77-1) for the junior and k=0.85 (95% CI; 0.70-1) for the senior radiologist.
      For the various anterior sites, the junior radiologist had k values between 0.60
      and 1, whereas those of the senior radiologist were between 0.87 and 1. For inter
      operator reproducibility, there was modest agreement between the two
      radiologists, k=0.46 (95% CI; 0.19-0.73), for the overall detection of anterior
      lesions; k varied between 0.43 and 0.61, depending on the site. CONCLUSION: Our
      results show that the characterization of anterior lesions by MRI is specific,
      but not very sensitive, with only moderate inter-operator reproducibility
      depending on the site. MRI can be used to diagnose anterior lesions, but cannot
      replace laparoscopy.

PMID- 30273679
TI  - GM1 locates to mature amyloid structures implicating a prominent role for
      glycolipid-protein interactions in Alzheimer pathology.
AB  - While the molecular mechanisms underlying Alzheimer's disease (AD) remain largely
      unknown, abnormal accumulation and deposition of beta amyloid (Abeta) peptides
      into plaques has been proposed as a critical pathological process driving disease
      progression. Over the last years, neuronal lipid species have been implicated in
      biological mechanisms underlying amyloid plaque pathology. While these processes
      comprise genetic features along with lipid signaling as well as direct chemical
      interaction of lipid species with Abeta mono- and oligomers, more efforts are
      needed to spatially delineate the exact lipid-Abeta plaque interactions in the
      brain. Chemical imaging using mass spectrometry (MS) allows to probe the spatial
      distribution of lipids and peptides in complex biological tissues comprehensively
      and at high molecular specificity. As different imaging mass spectrometry (IMS)
      modalities provide comprehensive molecular and spatial information, we here
      describe a multimodal ToF-SIMS- and MALDI-based IMS strategy for probing lipid
      and Abeta peptide changes in a transgenic mouse model of AD (tgAPPArcSwe). Both
      techniques identified a general AD-associated depletion of cortical sulfatides,
      while multimodal MALDI IMS revealed plaque specific lipid as well as Abeta
      peptide isoforms. In addition, MALDI IMS analysis revealed chemical features
      associated with morphological heterogeneity of individual Abeta deposits. Here,
      an altered GM1 to GM2/GM3 ganglioside metabolism was observed in the diffuse
      periphery of plaques but not in the core region. This was accompanied by an
      enrichment of Abeta1-40arc peptide at the core of these deposits. Finally, a
      localization of arachidonic acid (AA) conjugated phosphatidylinositols (PI) and
      their corresponding degradation product, lyso-phosphatidylinositols (LPI) to the
      periphery of Abeta plaques was observed, indicating site specific macrophage
      activation and ganglioside processing.

PMID- 30273680
TI  - Risk factors of pelvic pressure ulcer recurrence after primary skin flap surgery
      in people with spinal cord injury.
AB  - BACKGROUND: Flap surgery for deep pelvic pressure ulcers (PPUs) has been found
      effective, but the recurrence rate remains high and few risk factors have been
      identified. OBJECTIVE: We evaluated risk factors for PU recurrence after primary
      flap surgery in people with spinal cord injury (SCI). PATIENTS AND METHODS: This
      observational retrospective study based on medical charts included all
      individuals with SCI who underwent primary flap surgery for a PPU in the Herault
      department in France between 2006 and 2014. Overall, 100 biomedical,
      psychological, socioeconomic and care management factors were studied. The
      primary outcome was PPU recurrence (surgical site and/or other pelvic site). The
      secondary outcome was recurrence at the surgical site. Cox proportional hazards
      regression was used to determine associated factors, estimating hazard ratios
      (HRs) and 95% confidence intervals (CIs). RESULTS: We included 85 patients. Half
      had a PPU recurrence, and in one-third, the recurrence was at the surgical site.
      On multivariate analysis, global PPU recurrence was associated with colostomy
      (HR=2.79) and living with a partner (HR=2.29). Non-traumatic SCI and sacral wound
      were associated with PPU recurrence (HR=3.39, HR=0.48) and recurrence at the
      surgical site (HR=3.3, HR=0.3). CONCLUSION: Risk factors of PPU recurrence are
      based on both biomedical and social models. After primary flap surgery, the risk
      of recurrence justifies regular follow-up and strict monitoring.

PMID- 30273681
TI  - Ultrasonographic Imaging of the medial and lateral pouches in the knee: EURO
      MUSCULUS/USPRM protocol(s) revisited.

PMID- 30273684
TI  - Kinesio taping improves pain and function in patients with knee osteoarthritis: A
      meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To perform a meta-analysis from randomized controlled trials (RCTs) to
      evaluate the efficacy of Kinesio Taping in reducing pain and increasing knee
      function in patients with knee osteoarthritis (OA). METHODS: The electronic
      databases include PubMed, Embase, web of science and the Cochrane Library up to
      August 2018. Studies searched were considered eligible if they met the criteria
      as follows: Population: patients with knee OA; Intervention: intervention groups
      received Kinesio Taping for the treatment of knee OA; Comparisons: Control group
      received sham taping; 3) Outcomes: visual analog scale (VAS), McMaster
      Universities Arthritis Index (WOMAC) scale, range of motion and muscle strength;
      Study design: RCTs. The Cochrane Collaboration's tool was used to assess risk of
      bias. We assessed statistical heterogeneity for each RCT with the use of a
      standard Chi2 test and the I2 statistic. STATA statistical software 15.0 was used
      for meta-analysis. RESULTS: Five RCTs involving 308 patients were included. The
      present meta-analysis demonstrated that there were significant differences
      between Kinesio Taping groups and control groups in terms of visual analog scale
      (VAS), WOMAC scale and flexion range of motion. No significant difference was
      found regarding quadriceps femoris muscle between groups. CONCLUSION: Kinesio
      Taping is effective in improving for pain and joint function in patients with
      knee OA. Due to the limited quality of the evidence currently available, the
      results of our meta-analysis should be treated with caution.

PMID- 30273683
TI  - Neutrophil Gelatinase-Associated Lipocalin (NGAL) in predicting acute kidney
      injury following orthotopic liver transplantation: A systematic review.
AB  - BACKGROUND: Acute kidney injury (AKI) is common after orthotopic liver
      transplantation (OLT) usually occurring early post-transplant. Multiple causes
      include graft preservation injury, blood loss, hypotension but also severity of
      recipient liver disease. Early intervention in AKI has both short and long term
      patient benefits. Unfortunately there are no current clinical biomarkers of early
      AKI. AIM: To assess the value of NGAL in predicting AKI following OLT. METHODS:
      Ovid MEDLINE and EMBASE were searched between the years of 2000 and 2017 for
      studies using keywords: Neutrophil Gelatinase Associated Lipocalin or NGAL
      variants combined with synonyms for liver transplantation. RESULTS: 96 studies
      were identified. 11 studies including 563 patients were considered suitable for
      analysis. Both urinary (uNGAL) and plasma NGAL (pNGAL) measurement were found to
      predict AKI after liver transplantation. Optimal reported area under the receiver
      operator characteristics curve (AUROC) values of 0.5-0.83 and 0.54-0.86
      respectively. CONCLUSIONS: NGAL is a good predictor of early AKI post OLT
      although there is considerable variation in the published results. Further
      studies with prospectively defined cut-off values, standardized definitions of
      AKI and rigorous data reporting should be conducted to establish its clinical
      usefulness and limitations.

PMID- 30273682
TI  - Exploring sialyl-Tn expression in microfluidic-isolated circulating tumour cells:
      A novel biomarker and an analytical tool for precision oncology applications.
AB  - Circulating tumour cells (CTCs) originating from a primary tumour, lymph nodes
      and distant metastases hold great potential for liquid biopsies by providing a
      molecular fingerprint for disease dissemination and its temporal evolution
      through the course of disease management. CTC enumeration, classically defined on
      the basis of surface expression of Epithelial Cell Adhesion Molecule (EpCAM) and
      absence of the pan-leukocyte marker CD45, has been shown to correlate with
      clinical outcome. However, existing approaches introduce bias into the subsets of
      captured CTCs, which may exclude biologically and clinically relevant
      subpopulations. Here we explore the overexpression of the membrane protein O
      glycan sialyl-Tn (STn) antigen in advanced bladder and colorectal tumours, but
      not in blood cells, to propose a novel CTC isolation technology. Using a size
      based microfluidic device, we show that the majority (>90%) of CTCs isolated from
      the blood of patients with metastatic bladder and colorectal cancers express the
      STn antigen, supporting a link with metastasis. STn+ CTC counts were
      significantly higher than EpCAM-based detection in colorectal cancer, providing a
      more efficient cell-surface biomarker for CTC isolation. Exploring this concept,
      we constructed a glycan affinity-based microfluidic device for selective
      isolation of STn+ CTCs and propose an enzyme-based strategy for the recovery of
      viable cancer cells for downstream investigations. Finally, clinically relevant
      cancer biomarkers (transcripts and mutations) in bladder and colorectal tumours,
      were identified in cells isolated by microfluidics, confirming their malignant
      origin and highlighting the potential of this technology in the context of
      precision oncology.

PMID- 30273685
TI  - Higher Prevalence of Endometrial Polyps in Patients with Fallopian Tube
      Obstruction: A Case-Control Study.
AB  - STUDY OBJECTIVE: To study the association between endometrial polyps and
      fallopian tube patency diagnosed by hysteroscopy, conventional histology, and
      four-dimensional hysterosalpingo contrast sonography (4D-HyCoSy). DESIGN: Case
      control study (Canadian Task Force classification II-2). SETTING: University
      hospital. PATIENTS: A total of 323 women of reproductive age underwent 4D-HyCoSy
      and hysteroscopy between January 2015 and December 2017. INTERVENTION: A
      retrospective analysis of the association of endometrial polyps and fallopian
      tube obstruction (n = 154) or patency (n = 169) in patients who underwent 4D
      HyCoSy. MEASUREMENTS AND MAIN RESULTS: The prevalence of endometrial polyps was
      significantly higher in patients with bilateral fallopian tube obstruction than
      in patients with bilateral fallopian tube patency (42.9% [66 of 154] vs 20.1% [34
      of 169]; p < .0001). In univariate and multivariate analyses, the presence of
      endometrial polyps was found to be a risk factor for tubal obstruction with an
      odds ratio of 3.16 and 2.59, respectively. CONCLUSION: The prevalence of
      endometrial polyps is higher in infertile patients with fallopian tube
      obstruction than in patients with fallopian tube patency. History of endometrial
      polyps, ectopic pregnancy, and pelvic inflammatory disease are risk factors for
      tubal obstruction.

PMID- 30273686
TI  - The Association of Sonographic Evidence of Adenomyosis with Severe Endometriosis
      and Gene Expression in Eutopic Endometrium.
AB  - STUDY OBJECTIVE: To examine the presence of sonographic evidence of adenomyosis
      (SEOA) in patients undergoing laparoscopic surgery for the investigation of
      endometriosis and to assess if there is an association between SEOA and
      endometriosis severity. Using gene expression analysis, we also aimed to
      determine if gene expression in eutopic endometria differed in patients with and
      without adenomyosis. DESIGN: A prospective study (Canadian Task Force
      classification II-2). SETTING: A tertiary medical center. PATIENTS: Reproductive
      age women who underwent laparoscopic surgery after presenting to a pelvic pain
      focused gynecology clinic. INTERVENTIONS: Endometrial tissue, detailed patient
      questionnaires, pathology, and surgical notes were collected. Sonographic data
      from tertiary ultrasounds performed up to 12 months before surgery were
      retrospectively added (n = 234, researchers blinded to surgical and pathological
      findings). Gene array data from endometrial biopsies (n = 41) were used to
      analyze differential gene expression; patients were divided into 2 groups
      according to the presence or absence of SEOA. MEASUREMENTS AND MAIN RESULTS: Of
      the 588 patients recruited, 234 (40%) had an available pelvic scan and were
      included in this study. The average age of the included women was 30.6 years,
      with 35% having SEOA. Patients with SEOA were 5.4 years older (p = .02). There
      was no significant difference in the rates of endometriosis between groups;
      however, patients with SEOA were more likely to have stage IV endometriosis (41%
      vs 9.8%, p <.001). Patients with SEOA were also more likely to have other markers
      of severe endometriosis such as endometriomas and deep infiltrating endometriosis
      (p <.001). No significant difference was observed in endometrial gene expression
      between adenomyosis cases and controls after adjusting for menstrual c'ycle
      phases and the presence/absence of endometriosis. CONCLUSION: Sonographic
      features of adenomyosis may be included as a component of the clinical assessment
      when attempting to predict the presence of severe endometriosis. No differences
      in gene expression were observed. Further research is needed to characterize
      uterine adenomyosis and to explore molecular pathways involved in its
      pathogenesis.

PMID- 30273687
TI  - Determining Pain Catastrophizing From Daily Pain App Assessment Data: Role of
      Computer-Based Classification.
AB  - This study compared persons with chronic pain who consistently reported that
      their pain was worsening with those who reported that their pain was improving or
      remaining the same per daily assessment data from a smartphone pain app. All
      participants completed baseline measures and were asked to record their progress
      every day by answering whether their overall condition had improved, remained the
      same, or gotten worse (perceived change) on a visual analogue scale. One hundred
      forty-four individuals with chronic pain who successfully entered daily
      assessments were included. Those persons who were classified as worse showed
      significantly higher pain intensity scores, greater activity interference, higher
      disability and mood disturbance scores, and higher scores on the Pain
      Catastrophizing Scale both at baseline and after 3 months (P < .001). Repeated
      measures analyses and multilevel modeling of perceived change data over different
      time intervals of 20 assessments over 40 days, 10 assessments over 20 days, and 5
      assessments over 10 days were examined. These analyses demonstrated that group
      classification of better, same, and worse could be reliably determined, even with
      as few as 5 assessments. These results support the use of innovative mobile
      health technology to identify individuals who are prone to catastrophize about
      their pain. Perspective: This study demonstrated that daily assessment of overall
      perceived change with a smartphone pain app was positively correlated with the
      Pain Catastrophizing Scale and capturing short-term daily assessment trends data
      using computer-based classification methods might be a future way to help to
      identify individuals who tend to catastrophize about their pain.

PMID- 30273688
TI  - Self-Medication With Over-the-Counter Analgesics: A Survey of Patient
      Characteristics and Concerns About Pain Medication.
AB  - Pain is a common reason for self-medication with over-the-counter (OTC)
      analgesics. However, this self-treating population has remained largely
      uncharacterized. This cross-sectional observational study investigated
      individuals who self-medicate their pain with OTC analgesics to elucidate their
      pain characteristics and medication use. In addition, presence of and risk
      factors for concerns about pain medication were examined. The clinical profile of
      the participants (n = 1,889) was worse than expected with long-standing pain
      complaints (median pain duration of 9 years), pain located at multiple body sites
      (median of 4, and 13% with >=10 painful body areas), about one-third suffering
      from daily pain and about 40% experiencing substantial pain-related disability.
      Head (58.6% of sample), low back (43.6%), and neck (30.7%) were the most common
      pain locations. About 73% had a physician diagnosis, mainly migraine and
      osteoarthritis. Paracetamol (used by 68.6% of patients) and nonsteroidal anti
      inflammatory drugs (46.8%) were the most frequently used pain medications. About
      40% of our sample showed substantial concern about the perceived need for pain
      medication and the perceived potential for harmful effects (eg, fear for
      addiction). These findings highlight the importance for health professionals to
      systematically probe pain patients about their self-medication practices and
      explore attitudes about pain medication. Perspective: This study found that the
      clinical picture of people who self-medicate their pain with OTC analgesics
      looked worse than expected. We also identified substantial concerns about pain
      medication. Therefore, we recommend that health professionals systematically
      probe pain patients about their self-medication practices and explore concerns
      about pain medication.

PMID- 30273689
TI  - Child Abuse and Neglect Risk Assessment: Quality Improvement in a Primary Care
      Setting.
AB  - OBJECTIVES: Practicing SafetyTM (PS) is an AAP toolkit to help practices address
      child abuse and neglect (CAN) risk by increasing screening and providing
      resources. The objectives, in an urban practice serving low-income children, were
      to 1) standardize CAN risk assessment and developmental screening and 2) improve
      resource provision. METHODS: A quality improvement (QI) initiative to standardize
      CAN risk assessment, using materials adapted from PS (aPS) was conducted through
      the use of "SmartTools" in an electronic health record (EHR). The Edinburgh
      Postnatal Depression Scale and Parents Evaluation of Developmental Status were
      used to assess maternal depression and child development, respectively. Charts
      were reviewed in waves: pre-, immediate post-, and early post-implementation
      (waves 1-3), monthly for six months (waves 4-9), then quarterly for 12 months
      (waves 10-13) to assess screening and resource provision for six domains: infant
      crying, maternal depression, development, discipline, temper tantrums, and toilet
      training. RESULTS: A total of 581 charts were reviewed (waves 1-3: 92, 95, 94,
      respectively; waves 4-13: 30 each). Screening for infant crying, maternal
      depression, development, and discipline rose from 0% pre- to over 50% post
      implementation. Screening for temper tantrums and toilet training rose from 6% to
      72% and 36% to 82%, respectively. For all measures, resource provision improved
      over time, and all improvements were maintained for 1.5 years post
      implementation. CONCLUSIONS: Incorporating aPS into an EHR is a practical and
      effective approach to improving CAN risk assessment and resource provision. This
      QI initiative is an example of a practice-wide improvement that resulted in
      clinical practice change.

PMID- 30273690
TI  - Creation and validation of tool to assess resident competence in neonatal
      resuscitation.
AB  - BACKGROUND: The American Board of Pediatrics requires that pediatricians be able
      to initiate stabilization of a newborn. After residency, 45% of general
      pediatricians routinely attend deliveries. However, there is no standard approach
      or tool to measure resident proficiency in newborn resuscitation across training
      programs. In a national survey, we found a large variability in faculty
      assessment of the amount of supervision trainees need for various resuscitation
      scenarios. Objective documentation of trainee performance would permit competency
      based decisions on the level of supervision required and facilitate feedback on
      trainee performance. METHODS: A simplified tool was created following the
      Neonatal Resuscitation Program (NRP) algorithm, with emphasis on communication,
      leadership, knowledge of equipment, and initial stabilization. To achieve content
      validity, the tool was evaluated by the NRP steering committee. To assess
      internal structure of the tool, we filmed 10 simulated resuscitation scenarios 9
      of which contained errors. Experienced resuscitation team members used the tool
      to assess performance of the team leader in the videos. To evaluate the response
      process, the tool was used to assess experienced resuscitators in real time at
      academic and non-academic sites. RESULTS: The NRP steering committee approved the
      tool, providing evidence of content validity. Performance of the team leader in
      the simulated videos was assessed by 16 evaluators using the tool. There was an
      intra-class coefficient of 0.86 showing excellent agreement. There was no
      statistical difference in scores between 102 resuscitations led by experienced
      resuscitators at academic and non-academic hospitals (p=0.98), which demonstrates
      generalizability. CONCLUSIONS: The tool we have developed to assess performance
      in initiating newborn resuscitation shows evidence of construct validity based on
      assessment of content and internal structure (inter-observer agreement, response
      processes, and generalizability).

PMID- 30273691
TI  - Carbon monoxide releasing molecule A-1 attenuates acetaminophen-mediated
      hepatotoxicity and improves survival of mice by induction of Nrf2 and related
      genes.
AB  - Acute liver injury is frequently associated with oxidative stress. Here, we
      investigated the therapeutic potential of carbon monoxide releasing molecule A-1
      (CORM A-1) in oxidative stress-mediated liver injury. Overnight-fasted mice were
      injected with acetaminophen (APAP; 300 mg/kg; intraperitoneally) and were
      sacrificed at 4 and 12 h. They showed elevated levels of serum transaminases,
      depleted hepatic glutathione (GSH) and hepatocyte necrosis. Mice injected with
      CORM A-1 (20 mg/kg) 1 h after APAP administration, had reduced serum
      transaminases, preserved hepatic GSH and reduced hepatocyte necrosis. Mice that
      received a lethal dose of APAP (600 mg/kg), died by 10 h; but those co-treated
      with CORM A-1 showed a 50% survival. Compared to APAP-treated mice, livers from
      those co-treated with CORM A-1, had upregulation of Nrf2 and ARE genes (HO-1,
      GCLM and NQO-1). APAP-treated mice had elevated hepatic mRNA levels of
      inflammatory genes (Nf-kappaB, TNF-alpha, IL1-beta and IL-6), an effect blunted
      in those co-treated with CORM A-1. In tert-butyl hydroperoxide (t-BHP)-treated
      HepG2 cells, CORM A-1 augmented cell viability, reduced oxidative stress,
      activated the nuclear factor erythroid 2-related factor 2 (Nrf2) and anti-oxidant
      response element (ARE) genes. The molecular docking profile of CO in the kelch
      domain of Keap1 protein suggested that CO released from CORM A-1 mediated Nrf2
      activation. Collectively, these data indicate that CORM A-1 reduces oxidative
      stress by upregulating Nrf2 and related genes, and restoring hepatic GSH, to
      reduce hepatocyte necrosis and thus minimize liver injury that contributes to an
      overall improved survival rate.

PMID- 30273692
TI  - Resistin levels are not associated with obesity in central precocious puberty.
AB  - OBJECTIVE: To compare serum resistin concentrations between prepubertal girls
      with a BMI > 85th percentile and girls with precocious puberty (CPP) who have and
      have not undergone GnRH analog treatment. PATIENTS AND METHODS: This is a cross
      sectional study in girls with a BMI > 85th percentile and a median age of 8
      years. We included 31 girls with CPP who did not receive treatment (CPPoT), 23
      girls with CPP who were treated with leuprolide (CPPT), 22 prepubertal girls and
      24 pubertal girls. Anthropometric data and the fasting plasma concentrations of
      lipids, glucose, insulin, and resistin were measured. RESULTS: The z-BMI scores
      were similar among the groups (p = 0.344), and body fat percentage (BF%) was
      similar among CPPT, CPPoT and prepubertal girls (p = 0.151). Resistin and insulin
      levels were lower in girls with CPP (CPPT and CPPoT) than in prepubertal and
      pubertal girls (median resistin level: CPPT 11.8 pg/ml vs CPPoT 11 pg/ml vs
      prepubertal 16 pg/ml vs pubertal 16 pg/ml, p = 0.001; median insulin level: CPPT
      10.7 MUUI/mL vs CPPoT 10.2 MUUI/mL vs prepubertal 14.4 MUUI/mL vs pubertal 32
      MUUI/mL p = 0.02). ANCOVA analysis, after adjustments for pubertal stage, BF% and
      z-BMI, showed that CPP modifies resistin levels (F = 31.4; p = 0.0001)
      independently of these parameters (p < 0.05). CONCLUSIONS: In the group of girls
      with overweight or obesity, the resistin level was lower in girls with CPP than
      in prepubertal and pubertal girls. More studies are needed to understand the role
      of resistin in CPP patients.

PMID- 30273693
TI  - PAC1 regulates receptor tyrosine kinase transactivation in a reactive oxygen
      species-dependent manner.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a growth factor for
      lung cancer cells. PACAP-27 or PACAP-38 binds with high affinity to non-small
      cell lung cancer (NSCLC) cells, causing elevated cytosolic Ca2+, increased
      proliferation and increased phosphorylation of extracellular regulated kinase
      (ERK) and the epidermal growth factor receptor (EGFR). The role of reactive
      oxygen species (ROS) was investigated in these processes. Addition of PACAP-38 to
      NCI-H838 or A549 cells increased the tyrosine phosphorylation of the EGFR, HER2
      and ERK significantly by 4-, 3-, and 2-fold, respectively. The transactivation of
      the EGFR and HER2 was inhibited by gefitinib or lapatinib (tyrosine kinase
      inhibitors), PACAP (6-38) (PAC1 antagonist), N-acetylcysteine (NAC is an anti
      oxidant) or dipheyleneiodonium (DPI is an inhibitor of Nox and Duox enzymes).
      PACAP-38 addition to NSCLC cells increased ROS which was inhibited by PACAP (6
      38), NAC or DPI. Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2 mRNA was present
      in many NSCLC cell lines. PACAP-38 stimulated the growth of NSCLC cells whereas
      PACAP (6-38), gefitinib or DPI inhibited proliferation. The results show that ROS
      are essential for PAC1 to regulate EGFR and HER2 transactivation as well as
      proliferation of NSCLC cells.

PMID- 30273694
TI  - Crystal structures and Hirshfeld surface analyses of the di- and tri-hydrates of
      (5alpha,17E)-17-hydrazonoandrostan-3-ol: Significant differences in the hydrogen
      bonding patterns and supramolecular arrangements.
AB  - The crystal structures, Hirshfeld surface analyses and electrostatic potential
      surfaces of the di- and tri-hydrates of (5alpha,17E)-17-hydrazonoandrostan-3-ol,
      3, namely [3.(H2O)2] and [3.(H2O)3], are reported. The trihydrate, isolated from
      a solution of 3 in moist methanol, recrystallizes in the orthorhombic space
      group, P212121, while that of the dihydrate, isolated from a 1:1 aqueous methanol
      solution, recrystallizes in the monoclinic space group, P21. The asymmetric unit
      of the trihydrate involves one steroid and three water molecules, while that of
      the dihydrate has two similar but independent steroid molecules and four hydrate
      molecules. Very similar conformations are found for the steroid molecules in both
      hydrates. As expected, the different mole ratios of water: steroid have major
      influences on the structures. In both cases, complex crystal structures are
      constructed from various classical hydrogen bonds, involving the hydrate
      molecules and the hydroxy and hydrazonyl moieties of the steroid. In the
      trihydrate, there are no direct connections between the steroid molecules,
      instead the water molecules link the steroid molecules, with only weak van der
      Waals forces between the steroid molecules. There are some direct links between
      the steroid molecules in the dihydrate, involving OH(steroid hydroxyl)?O(steroid
      oxo) hydrogen bonds, in a head to head fashion, and OH?N(hydrazonyl) hydrogen
      bonds, in a head to tail fashion. However, the major occurrence throughout the
      structure is of steroid molecules linked by water molecules.

PMID- 30273695
TI  - Chemical synthesis of C3-oxiranyl/oxiranylmethyl-estrane derivatives targeted by
      molecular modeling and tested as potential inhibitors of 17beta-hydroxysteroid
      dehydrogenase type 1.
AB  - 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is a promising
      therapeutic target known to play a pivotal role in the progression of estrogen
      dependent diseases such as breast cancer, and endometriosis. This enzyme is
      responsible for the last step in the biosynthesis of the most potent estrogen,
      estradiol (E2) and its inhibition would prevent the growth of estrogen-sensitive
      tumors. Based on molecular modeling with docking experiments, we identified two
      promising C3-oxiranyl/oxiranylmethyl-estrane derivatives that would bind
      competitively and irreversibly in the catalytic site of 17beta-HSD1. They have
      been synthesized in a short and efficient route and their inhibitory activities
      over 17beta-HSD1 have been assessed by an enzymatic assay. Compound 15, with an
      oxiranylmethyl group at position C3, was more likely to bind the catalytic site
      and showed an interesting, but weak, inhibitory activity with an IC50 value of
      1.3 uM (for the reduction of estrone into E2 in T-47D cells). Compound 11, with
      an oxiranyl at position C3, produced a lower inhibition rate, and the IC50 value
      cannot be determined. When tested in estrogen-sensitive T-47D cells, both
      compounds were also slightly estrogenic, although much less than the estrogenic
      hormone E2.

PMID- 30273696
TI  - Anti-inflammatory furostanol saponins from the rhizomes of Smilax china L.
AB  - Seven new furostanol saponins (1-7), chongrenosides A-G, were isolated from the
      rhizomes of Smilax china L., together with nine known furostanol saponins (8-16).
      The structures of the new furostanol saponins (1-7) were elucidated by extensive
      spectroscopic data analyses (1D and 2D NMR, HRESIMS) and chemical evidence.
      Compounds 1-6 and 8-16 were evaluated for TNF-alpha mRNA expression inhibitory
      activity on LPS induced RAW264.7 cells. Of them, 1, 4, 6, and 11 inhibited the
      TNF-alpha mRNA expression by 88%, 87%, 67%, and 93%, respectively, at the
      concentration of 10 uM.

PMID- 30273697
TI  - Olfactory function and cognition in relapsing-remitting and secondary-progressive
      multiple sclerosis.
AB  - BACKGROUND: Both cognition and olfaction are impaired in multiple sclerosis (MS).
      However, little is known about the relationship between smell identification
      ability and measures of cognitive function in this disease. OBJECTIVE: To assess
      olfactory function in MS and to evaluate its relationship with cognitive and
      physical disability. METHODS: Fifty-five MS patients and 20 healthy controls
      (HCs) were tested. The University of Pennsylvania smell identification test
      (UPSIT) was administered to assess olfactory function. Cognitive function was
      tested using the symbol digit modalities test (SDMT), California verbal learning
      test-II (CVLT II), brief visuospatial memory test (BVMT), paced auditory serial
      addition test (PASAT), and controlled oral word association test (COWAT). Fatigue
      and depressive symptoms were evaluated using the Modified Fatigue Impact Scale
      and the Beck Depression Inventory II, respectively. RESULTS: MS patients had
      lower UPSIT scores than those of the HCs (28.76 +/- 5.48 vs 31.7 +/- 2.18, p =
      0.02), with secondary-progressive and cognitively impaired MS patients showing
      the greatest impairment. Scores on the SDMT, CVLTII, BVMT and COWAT were related
      to the olfactory test scores. CONCLUSION: We confirm that olfactory function is
      impaired in MS, particularly in progressive phenotypes, and show, for the first
      time, that such dysfunction is related to a broad range of cognitive measures.
      Our data suggest that olfactory dysfunction might be considered as an indirect
      measure of MS severity. Longitudinal studies are needed to confirm this
      possibility.

PMID- 30273698
TI  - A systematic review of DURAL puncture epidural analgesia for labor.
AB  - STUDY OBJECTIVE: This systematic review aimed to summarize the evidence derived
      from randomized controlled trials (RCTs) comparing dural puncture epidural
      analgesia (DPEA) and conventional lumbar epidural analgesia (LEA) for women
      undergoing labor. INTERVENTIONS: The MEDLINE and EMBASE databases were searched
      from inception to July 2018 in order to find RCTs published in the English
      language, which investigated DPEA in laboring women. MAIN RESULTS: Six RCTs were
      included in the final analysis. Their collective results remain ambiguous. Dural
      puncture with small (i.e., 26- or 27-gauge) spinal needles seems to confer either
      minimal benefits or improved analgesic quality and lower pain scores in the first
      10 min. Dural puncture with 25-gauge spinal needles has been reported to provide
      higher success rate than conventional LEA in one trial; however two other studies
      could only agree on the fact that DPEA results in improved sacral blockade and
      fewer unilateral blocks compared to LEA. CONCLUSIONS: The current evidence
      regarding DPEA for labor analgesia remains ambiguous. Future research should
      investigate the optimal (spinal) needle size for dural puncture as well as
      factors governing transmeningeal flux of local anesthetics and opioids in the
      presence of a dural hole.

PMID- 30273699
TI  - Auditory central gain compensates for changes in cochlear output after prolonged
      low-level noise exposure.
AB  - Remarkably, the central auditory system can modify the strength of its sound
      evoked neural response based on prior acoustic experiences, a phenomenon referred
      to as central gain. Gain changes are well documented following traumatic noise
      exposure, but much less is known about central gain dynamics following prolonged
      exposure to low-level noise, a common acoustic experience in many urban and work
      environments. We recently reported that the neural output of the cochlea is
      reduced, while gain was enhanced in the inferior colliculus (IC) following a 5
      week exposure to 75 dB noise. To determine if similar effects were present at
      even lower intensities, we exposed rats to a 65 dB noise expecting to see little
      to no change in the cochlea or IC. The exposure had little effect on distortion
      product otoacoustic emissions and did not cause any hair cell loss. However, the
      amplitude of the CAP, which reflects the neural output of cochlea, was depressed
      by 50-75%. Surprisingly, neural responses from the IC were enhanced up to 70%,
      mainly at frequencies within the noise exposure band. One-week post-exposure, CAP
      amplitudes returned to normal at frequencies within or above the exposure band,
      whereas responses evoked by frequencies below the exposure band were enhanced by
      more than 80%. In contrast, IC responses below the exposure frequency were
      depressed 10-20% whereas responses within the exposure frequency band were
      enhanced 10-20%. Thus, the central auditory system dynamically up- and down
      regulates its gain to maintain supra-threshold neural responses within a narrow
      homeostatic range; a function that likely contributes to the prevention of sounds
      from being perceived as muffled or too loud.

PMID- 30273700
TI  - Activation of the unfolded protein response in canine degenerative myelopathy.
AB  - Canine degenerative myelopathy (DM) is an adult-onset progressive and fatal
      neurodegenerative disorder. Superoxide dismutase 1 (SOD1) mutations have been
      reported in affected dogs and immunohistochemical analyses revealed the
      accumulation of mutant SOD1 (E40K) in spinal neurons and astrocytes. Therefore,
      this disease is regarded as a unique spontaneous large-animal model of SOD1
      mediated amyotrophic lateral sclerosis (ALS) in humans. Recent studies reported
      that endoplasmic reticulum (ER) stress is a key pathomechanism underlying motor
      neuron death in ALS. The present study demonstrated the up-regulated expression
      of the ER stress marker GRP78/BiP (BiP) in the spinal cords of DM-affected dogs.
      Immunohistochemistry of serial spinal cord sections revealed strong BiP
      expression in microglia and astrocytes in DM compared to normal control dogs,
      whereas such difference was not observed in spinal neurons. The results of
      transcriptional analyses of DM spinal tissues showed increased expression levels
      of apoptosis signal-regulating kinase 1 (ASK1) and spliced X-box binding protein
      (XBP1s). E40K-transfected Neuro2A cells expressed higher levels of BiP than wild
      type SOD1-transfected cells. These results suggest that the activation of the
      unfolded protein response (UPR) in microglia and astrocytes plays crucial roles
      in UPR-mediated inflammation in the spinal cords of DM-affected dogs.

PMID- 30273701
TI  - Neurokinin-1 receptor antagonism improves postoperative neurocognitive disorder
      in mice.
AB  - Postoperative neurocognitive disorder (PND) is a major complication in surgical
      patients, especially the elderly, leading to mild memory impairment after
      surgery. The underlying pathophysiology remains unknown, although
      neuroinflammation and blood-brain barrier (BBB) disruption have been increasingly
      implicated in PND. Emerging evidence suggests that neurokinin-1 receptor (NK-1R),
      the principal target of proinflammatory neuropeptide substance P (SP), plays a
      pivotal role in modulating neuroinflammation and BBB integrity. In this study, we
      used an established mouse model for PND to investigate the effects of a selective
      NK-1R antagonist L-733,060 on PND-like features after peripheral surgery.
      Hippocampal SP started to increase at 6 h, peaked at 1 day, and returned to
      baseline at 3 days after surgery. At 1 day after surgery, NK-1R expression was
      increased in the hippocampus. At this time point, NK-1R antagonist pretreatment
      attenuated microgliosis and prevented neutrophil infiltration after surgery.
      Similarly, proinflammatory cytokines interleukin-1 beta and interleukin-6 were
      reduced in the hippocampus in NK-1R antagonist-treated mice at 6 h after surgery.
      Furthermore, surgery-induced BBB disruption, assessed by albumin deposition and
      expression of tight junction protein claudin-5, was attenuated by NK-1R
      antagonism at postoperative day 1. Finally, trace fear conditioning test revealed
      NK-1R antagonism reversed surgery-induced cognitive impairment at 3 days after
      surgery. Our findings suggest that inhibition of NK-1R signaling protects
      hippocampus-dependent memory from surgical insult, probably through modulations
      of neuroinflammation and BBB integrity.

PMID- 30273702
TI  - Peroxisomicine A1 (toxin T-514) induces cell death of hepatocytes in vivo by
      triggering the intrinsic apoptotic pathway.
AB  - Karwinskia parvifolia possesses the highest concentration levels of the
      anthracenone T-514 (PA1). Studies have demonstrated the induction of apoptosis by
      PA1 in cancer cell lines. The aim was to investigate the effects of PA1 on the
      apoptosis of the mouse liver in vivo and its underlying pathway. Sixty CD-1 mice
      were divided into three groups: untreated, vehicle, and treated with PA1. The
      animals were euthanized at 4, 8, 12, and 24 h post-treatment. To confirm the
      toxic effect of PA1 we determined the activity of catalase. Liver sections were
      prepared for morphological examination and for immunohistochemical evaluation of
      anti and pro-apoptotic markers. DNA fragmentation was detected by TUNEL assay and
      electrophoresis. Pre-apoptotic mitochondrial alterations and cytochrome c oxidase
      activity were analyzed by transmission electron microscopy. PA1 induced pre
      apoptotic mitochondrial alterations, a high activity of the cytochrome oxidase,
      and apoptosis in hepatocytes. PA1 caused p53 over-expression and down regulation
      of PCNA. PA1 also increased the expression levels of the pro-apoptotic markers
      Bax and Bak, whereas the anti-apoptotic molecule Bcl-2 was decreased. PA1 induces
      apoptosis by activating the intrinsic mitochondrial apoptotic pathway. These
      results will be useful for studies regarding the use of PA1 as an antineoplastic
      agent.

PMID- 30273703
TI  - Centipede envenomation: Clinical importance and the underlying molecular
      mechanisms.
AB  - Centipede bites are usually characterized by mildly to moderately painful
      encounters with humans, however, they are relatively infrequent. The vast
      majority of centipede envenomations do not cause severe symptoms and only in very
      rare cases more serious symptoms such as myocardial ischemia and infarction,
      hematuria, hemoglobinuria, rhabdomyolysis, hemorrhage, pruritus, eosinophilic
      cellulitis, as well as anaphylaxis are observed. More prevalent are symptoms
      including pain, paresthesia, lethargy, localized necrosis, headache, dizziness
      and nausea. The numerous symptoms and complications elicited by these
      envenomations indicate that centipede venom possesses an arsenal of chemical
      components with functional diversity. Centipede venom is a rich and complex
      natural source of bioactive proteins, peptides and other small molecules that aid
      in predation or defense. The venom can induce myotoxic, cardiotoxic, neurotoxic
      and other toxic effects. The constituents target different cellular processes and
      pathways which in turn trigger a cascade of physiological reactions in the
      victim. The venom components are potent and selective on peripheral targets;
      thus, they are valuable in studying the molecular basis of these envenomation
      symptoms and complications. This review highlights the clinical importance of
      centipede envenomation and the recent discoveries on the underlying molecular
      mechanisms of the resulting symptoms which is crucial in therapy.

PMID- 30273704
TI  - Genotoxicity and cytotoxicity of three microcystin-LR containing cyanobacterial
      samples from Antioquia, Colombia.
AB  - The presence of cyanobacterial blooms and cyanotoxins in water presents a global
      problem due to the deterioration of ecosystems and the possibility of poisoning
      in human and animals. Microcystin LR is the most widely distributed cyanotoxin
      and liver cells are its main target. In the present study, HepG2 cells were used
      to determine DNA damage of three crude extracts of cyanobacterial blooms
      containing MC-LR, through comet assay. The results show that all extracts at a
      concentration of 500 MUg mL-1 caused low damage in hepatocytes exposed for 24 h,
      but produced total mortality even at low concentrations at 48 h. Moreover,
      balloons corresponding to cell apoptosis were found. Through HPLC/MS, MC-LR was
      detected in all samples of cyanobacterial blooms at concentrations of (5,65 MUg
      ml-1) in sample 1, (1,24 MUg ml-1) in sample 2 and (57,29 MUg ml-1) in sample 3.
      In addition, in all samples high molecular weights peaks were detected, that may
      correspond to other microcystins. Besides, the cytotoxic effect of a
      cyanobacterial bloom and some of its chromatographic fractions from the crude
      extracts were evaluated in U-937, J774, Hela and Vero cell lines, using the
      enzymatic micromethod (MTT). The highest toxicity was detected in U-937 cells
      (LC50 = 29.7 MUg mL-1) and Vero cells (LC50 = 39.7 MUg mL-1). Based on these
      results, it is important to remark that genotoxic and cytotoxicity assays are
      valuable methods to predict potential biological risks in waters contaminated
      with blooms of cyanobacteria, since chemical analysis can only describe the
      presence of cyanotoxins, but not their biological effects.

PMID- 30273706
TI  - Low serum phosphate and magnesium levels are associated with peripheral
      neuropathy in patients with type 2 diabetes mellitus.
AB  - AIMS: To determine the relationship of serum phosphate, serum magnesium and
      peripheral nerve function in patients with type 2 diabetes mellitus (T2DM).
      METHODS: A total of 254 patients diagnosed with T2DM were included. Peripheral
      nerve function was evaluated by nerve conduction study with the use of
      electromyography. Composite z scores of conduction velocity, latency, and
      amplitude were constructed, respectively. Demographic, medical and laboratory
      data including serum phosphate and magnesium were collected. RESULTS: Serum
      phosphate and serum magnesium levels were significantly lower in patients with
      diabetic peripheral neuropathy (DPN) (P < 0.01). And the percentages of DPN
      patients were lower in high tertile of serum phosphate and serum magnesium (P <
      0.05). Furthermore, composite z score of conduction velocity (CV) (P = 0.012)
      were positively associated with serum phosphate levels and the composite z score
      of amplitude (P < 0.001) and CV (P = 0.041) were positively associated with serum
      magnesium levels. After adjusting potential related factors (age, gender,
      smoking, diabetes duration, body mass index, systolic blood pressure, glycated
      hemoglobin, total cholesterol, estimated glomerular filtration rate), serum
      levels of phosphate and magnesium were still related to status of DPN in logistic
      regression (P < 0.05). CONCLUSION: Lower serum phosphate and magnesium
      significantly correlated with parameters of nerve conduction in T2DM patients.
      Serum phosphate and magnesium might underlie the pathophysiologic features of
      DPN.

PMID- 30273705
TI  - Gelsemium poisoning mediated by the non-toxic plant Cassytha filiformis
      parasitizing Gelsemium elegans.
AB  - INTRODUCTION: Gelsemium poisoning is caused by consumption of the deadly
      Gelsemium species such as Gelsemium elegans, leading to significant
      gastrointestinal, neurological and cardio-respiratory toxicities. In 2011
      (Cluster 1) and 2012 (Cluster 2), the authors encountered two clusters of
      gelsemium poisoning after consumption of the non-toxic parasitic plant Cassytha
      filiformis. The current study aims to examine the mechanism of gelsemium
      poisoning mediated by a benign parasitic plant. METHODS: Qualitative analysis of
      toxic gelsemium alkaloids using liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) was performed on the herbal and urine samples from both clusters to
      confirm exposure. Morphological examination, qualitative analysis of aporphine
      alkaloids using liquid chromatography-ion trap-time of flight mass spectrometry
      (LC-IT-TOF/MS) and Sanger sequencing were performed on the plant sample from
      Cluster 2 to confirm its identity. A field study was conducted in local
      countryside and C. filiformis was collected for histological, LC-MS/MS and LC-IT
      TOF/MS analyses to study its interaction with G. elegans. RESULTS: Gelsemium
      alkaloids that are not naturally present in C. filiformis were detected in the
      patients' herbal and urine samples. Misidentification and contamination with G.
      elegans during the preparation process were excluded by morphological examination
      of the plant sample from Cluster 2. Its identity as C. filiformis was verified
      with LC-IT-TOF/MS and molecular analyses. Histological, LC-MS/MS and LC-IT-TOF/MS
      analyses of C. filiformis collected during the field study confirmed that its
      haustoria penetrated the vascular bundles of G. elegans and absorbed its
      gelsemium toxins. CONCLUSIONS: The non-toxic plant C. filiformis absorbed toxic
      gelsemium alkaloids from its host, G. elegans, and led to gelsemium poisoning in
      our patients. Our study provides new insights into the toxicology of such plants.
      Benign parasitic plants may lead to potentially life-threatening poisoning if it
      parasitizes toxic hosts and absorbs their phytotoxins. The public awareness of
      risks associated with the use of these medicinal parasitic plants should be
      raised.

PMID- 30273707
TI  - Petition to replace current OGTT criteria for diagnosing prediabetes with the 1
      hour post-load plasma glucose >= 155 mg/dl (8.6 mmol/L).
AB  - Many individuals with prediabetes, as presently defined, will progress to
      diabetes (T2D) despite the considerable benefit of lifestyle modification.
      Therefore, it is paramount to screen individuals at increased risk with a more
      sensitive method capable of identifying prediabetes at an even earlier time point
      in the lengthy trajectory to T2D. This petition reviews findings demonstrating
      that the 1-hour (1-h) postload plasma glucose (PG) >= 155 mg/dl (8.6 mmol/L) in
      those with normal glucose tolerance (NGT) during an oral glucose tolerance test
      (OGTT) is highly predictive for detecting progression to T2D, micro- and
      macrovascular complications and mortality in individuals at increased risk.
      Furthermore, the STOP DIABETES Study documented effective interventions that
      reduce the future risk of T2D in those with NGT and a 1-h PG >= 155 mg/dl (8.6
      mmol/L). The 1-h OGTT represents a valuable opportunity to extend the proven
      benefit of diabetes prevention to the sizeable and growing population of
      individuals at increased risk of progression to T2D. The substantial evidence
      provided in this petition strongly supports redefining current diagnostic
      criteria for prediabetes with the elevated 1-h PG level. The authors therefore
      advocate a 1-h OGTT to detect prediabetes and hence, thwart the global diabetes
      epidemic.

PMID- 30273708
TI  - Cost-effectiveness of a faith-based lifestyle intervention for diabetes
      prevention among African Americans: A within-trial analysis.
AB  - AIMS: We assessed costs and cost-effectiveness of implementing Fit Body and Soul
      (FBAS), a church-based 18-session lifestyle education intervention for African
      Americans. METHODS: We calculated incremental cost-effectiveness ratios (ICER)
      using data from a cluster randomized controlled trial comparing FBAS with health
      education (HE) among 604 overweight participants in 20 churches. The ICER was the
      adjusted difference in costs to deliver FBAS versus HE over the difference in
      weight change (kilograms [kg]) at one-year follow-up. Costs included those
      incurred for participant identification and program implementation. We fitted
      linear mixed-effects regression models, accounting for clustering of participants
      within churches and for age, sex, and educational attainment. We repeated these
      analyses for secondary outcomes (waist circumference [cm], physical activity
      [MET], glucose, blood pressure, and quality of life). RESULTS: Per-person
      intervention cost of FBAS was $50.39 more than HE ($442.22 vs. $391.83 per
      person), and adjusted differences in weight change (1.9 kg [95% CI: 1.0 to 2.8])
      and waist circumference (2.4 cm [95% CI: 1.3 to 3.4]) were both significant. FBAS
      did not result in statistically significant differences in physical activity,
      glucose, blood pressures, or quality of life. We estimated that compared to HE,
      FBAS costs an additional $26.52 per kg weight lost and $21.00 per cm reduction in
      waist circumference. CONCLUSIONS: For a modest increase in cost, FBAS led to
      greater weight and waist reductions among African Americans in a church setting.
      ClinicalTrials.gov Identifier NCT01730196.

PMID- 30273711
TI  - Precision gaming for health: Computer games as digital medicine.
AB  - Health based games have significant potential as therapeutic interventions due to
      the inherent mechanisms associated with social and individual game play and their
      capacity for sensor integration, data capture analysis and patient feedback.
      Moreover, they are low cost and they can be deployed at the point of care across
      an evolving digital ecosystem. However, a robust evidence base to support their
      wider adoption as a clinical intervention for chronic diseases is lacking and
      significant methodological barriers exist for health games developers creating
      efficacious 'digital medicines'. Game design is complex and it must utilise
      validated game mechanics balanced with a creative and engaging game design. The
      aim of this review is therefore to outline the fundamental steps of game
      development for health professionals and to critically appraise the methodology
      for assessing health games as medical interventions. This requires (1) The
      adoption of clearly defined global language for health games development based on
      a targeted function as therapeutic agents. (2) The development of
      multidisciplinary teams with a broad portfolio of development and clinical skill
      sets. (3) The creation of health game engines specifically built to facilitate
      clinical game development. (4) Robust trial design and assessment of
      translational impact: If games are to be prescribed, their efficacy and toxicity
      must be based on a rigorous assessment of their use within a real world clinical
      environment. Trials for precision health games have specific challenges around
      blinding, learning curves, bias and confounding that are particularly
      problematic. We propose the adoption of the IDEAL-GAMES framework for game
      development that systematically assess and validates games through open
      registries. In conclusion we propose a new framework for assessing the robustness
      and clinical efficacy of games for health as clinical interventions in the
      clinical environment.

PMID- 30273712
TI  - Morphological study of the ovary in Hanseniella caldaria (Myriapoda; Symphyla):
      The position of oocyte-growth and evolution of ovarian structure in Arthropoda.
AB  - In Arthropoda, the ovary is classified into Chelicerata-type and Mandibulata
      type, based on the oocyte-growth position within the ovary. By contrast, oocytes
      of Diplopoda and Chilopoda grow within the hemocoelic space. However, as the
      position of oocyte-growth in Symphyla and Pauropoda has not been confirmed,
      whether the hemocoelic nature of oocyte-growth is common among myriapods remains
      ambiguous. This study described the ovarian structure of Hanseniella caldaria to
      reveal the oocyte-growth position in Symphyla. The oocyte is surrounded by the
      follicle epithelium, and the inner surface of the follicle epithelium, i.e., the
      space between follicle cells and oocytes, is lined with a basement membrane. The
      follicle epithelial layer continues to the ovarian epithelium via the follicle
      extension with a continuous layer of basement membrane. Data on the architecture
      of the follicle suggest that the follicle pouch opens to the hemocoel. Hence, the
      oocyte of H. caldaria grows within the hemocoelic space. Based on our findings in
      H. caldaria and previous studies in a millipede and in centipedes, the hemocoelic
      nature of oocyte-growth is considered as a common feature among myriapods and a
      synapomorphy of the Myriapoda for which morphological synapomorphies have been
      ambiguous.

PMID- 30273710
TI  - Unexpected relevant role of gene mosaicism in patients with primary
      immunodeficiency diseases.
AB  - BACKGROUND: Postzygotic de novo mutations lead to the phenomenon of gene
      mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism,
      which differ in terms of the body distribution of postzygotic mutations.
      Mosaicism has been reported occasionally in patients with primary
      immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement
      has not been systematically addressed. OBJECTIVE: We sought to investigate the
      incidence of gene mosaicism in patients with PIDs. METHODS: The amplicon-based
      deep sequencing method was used in the 3 parts of the study that establish (1)
      the allele frequency of germline variants (n = 100), (2) the incidence of
      parental gonosomal mosaicism in families with PIDs with de novo mutations (n =
      92), and (3) the incidence of mosaicism in families with PIDs with moderate-to
      high suspicion of gene mosaicism (n = 36). Additional investigations evaluated
      body distribution of postzygotic mutations, their stability over time, and their
      characteristics. RESULTS: The range of allele frequency (44.1% to 55.6%) was
      established for germline variants. Those with minor allele frequencies of less
      than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%)
      of 128 families with PIDs, with a variable minor allele frequency (0.8% to
      40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with
      de novo mutations, and a high incidence of mosaicism (63.9%) was detected among
      families with moderate-to-high suspicion of gene mosaicism. In most analyzed
      cases mosaicism was found to be both uniformly distributed and stable over time.
      CONCLUSION: This study represents the largest performed to date to investigate
      mosaicism in patients with PIDs, revealing that it affects approximately 25% of
      enrolled families. Our results might have serious consequences regarding
      treatment and genetic counseling and reinforce the use of next-generation
      sequencing-based methods in the routine analyses of PIDs.

PMID- 30273713
TI  - Review: In vitro generation of red blood cells for transfusion medicine:
      Progress, prospects and challenges.
AB  - In vitro generation of red blood cells (RBCs) has the potential to circumvent the
      shortfalls in global demand for blood for transfusion applications. The
      conventional approach for RBC generation has been from differentiation of
      hematopoietic stem cells (HSCs) derived from cord blood, adult bone marrow or
      peripheral blood. More recently, RBCs have been generated from human induced
      pluripotent stem cells (hiPSCs) as well as from immortalized adult erythroid
      progenitors. In this review, we highlight the recent advances to RBC generation
      from these different approaches and discuss the challenges and new strategies
      that can potentially make large-scale in vitro generation of RBCs a feasible
      approach.

PMID- 30273715
TI  - A simple geometric analysis method for measuring and mitigating RF induced
      currents on Deep Brain Stimulation leads by multichannel transmission/reception.
AB  - The purpose of this work is to present a new method that can be used to estimate
      and mitigate RF induced currents on Deep Brain Stimulation (DBS) leads. Here, we
      demonstrate the effect of RF induced current mitigation on both RF heating and
      image quality for a variety of brain MRI sequences at 3 T. We acquired pre-scan
      images around a DBS lead (in-situ and ex-vivo) using conventional Gradient Echo
      Sequence (GRE) accelerated by parallel imaging (i.e GRAPPA) and quantified the
      magnitude and phase of RF induced current using the relative location of the B1+
      null with respect to the lead position. We estimated the RF induced current on a
      DBS lead implanted in a gel phantom as well as in a cadaver head study for a
      variety of RF excitation patterns. We also measured the increase in tip
      temperature using fiber-optic probes for both phantom and cadaver studies. Using
      the magnitude and phase information of the current induced separately by two
      transmit channels of the body coil, we calculated an implant friendly (IF)
      excitation. Using the IF excitation, we acquired T1, T2 weighted Turbo Spin Echo
      (TSE), T2 weighted SPACE-Dark Fluid, and Ultra Short Echo Time (UTE) sequences
      around the lead. Our induced current estimation demonstrated linear relationship
      between the magnitude of the induced current and the square root SAR at the tip
      of the lead as measured in phantom studies. The "IF excitation pattern"
      calculated after the pre-scan mitigated RF artifacts and increased the image
      quality around the lead. In addition, it reduced the tip temperature
      significantly in both phantom and cadaver studies compared to a conventional
      quadrature excitation while keeping equivalent overall image quality. We present
      a relatively fast method that can be used to calculate implant friendly
      excitation, reducing image artifacts as well as the temperature around the DBS
      electrodes. When combined with a variety of MR sequences, the proposed method can
      improve the image quality and patient safety in clinical imaging scenarios.

PMID- 30273714
TI  - Neural correlates of developing theory of mind competence in early childhood.
AB  - Theory of mind (ToM) encompasses a range of abilities that show different
      developmental time courses. However, relatively little work has examined the
      neural correlates of ToM during early childhood. In this study, we investigated
      the neural correlates of ToM in typically developing children aged 4-8 years
      using resting-state functional magnetic resonance imaging. We calculated whole
      brain functional connectivity with the right temporo-parietal junction (RTPJ), a
      core region involved in ToM, and examined its relation to children's early,
      basic, and advanced components of ToM competence assessed by a parent-report
      measure. Total ToM and both basic and advanced ToM components, but not early,
      consistently showed a positive correlation with connectivity between RTPJ and
      posterior cingulate cortex/precuneus; advanced ToM was also correlated with RTPJ
      to left TPJ connectivity. However, early and advanced ToM components showed
      negative correlation with the right inferior/superior parietal lobe, suggesting
      that RTPJ network differentiation is also related to ToM abilities. We confirmed
      and extended these results using a Bayesian modeling approach demonstrating
      significant relations between multiple nodes of the mentalizing network and ToM
      abilities, with no evidence for differences in relations between ToM components.
      Our data provide new insights into the neural correlates of multiple aspects of
      ToM in early childhood and may have implications for both typical and atypical
      development of ToM.

PMID- 30273716
TI  - Comparability of the Australian National Cancer Symptom Trials (CST) Group's
      Study Populations to National Referrals to Non-CST Specialist Palliative Care
      Services Participating in the Palliative Care Outcomes Collaboration.

PMID- 30273717
TI  - Concordance Between Proxy Level of Care Preference and Advance Directives Among
      Nursing Home Residents With Advanced Dementia: A Cluster Randomized Clinical
      Trial.
AB  - CONTEXT: Care consistent with goals is the desired outcome of advance care
      planning (ACP). OBJECTIVES: The objectives of this study were to examine
      concordance between advance directives and proxy care preferences among nursing
      home residents with advanced dementia and to determine the impact of an ACP video
      on concordance. METHODS: Data were from Educational Video to Improve Nursing home
      Care in End-stage dementia, a cluster randomized clinical trial conducted in 64
      Boston-area facilities (32/arm) from 2013 to 2017. Participants included advanced
      dementia residents and their proxies (N = 328 dyads). At the baseline and
      quarterly (up to 12 months), proxies stated their preferred level of care for the
      resident (comfort, basic, or intensive) and advance directives for specific
      treatments (resuscitation, hospitalization, tube-feeding, intravenous hydration,
      antibiotics) were abstracted from the charts. At the baseline, proxies in
      intervention facilities viewed an ACP video. Their care preferences after viewing
      it were shared via a written communication with the primary care team. At each
      assessment, concordance between directives and proxy preferences was determined.
      RESULTS: Among the residents (mean age, 86.6 years; 19.5% male), the most
      prevalent directive was DNR (89.3%) and foregoing antibiotics was least common
      (parenteral, 8.2%; any type, 4.0%). Concordance between directives and each level
      of care preference was as follows: comfort, 7%; basic, 49%; and intensive, 58%.
      When comfort care was preferred, concordance was higher in intervention versus
      control facilities (10.8% vs. 2.5%; adjusted odds ratio, 2.48; 95% CI, 1.01
      6.09). CONCLUSION: Better alignment between preferences for comfort-focused care
      and advance directives is needed in advanced dementia. An ACP video may help
      achieve that goal.

PMID- 30273718
TI  - Prognostication Using SCORTEN Severity of Illness Score in Patients With Stevens
      Johnson Syndrome and Toxic Epidermal Necrolysis.

PMID- 30273719
TI  - Rapid respiratory transition at birth as evaluated by electrical activity of the
      diaphragm in very preterm infants supported by nasal CPAP.
AB  - OBJECTIVE: To investigate breathing patterns during respiratory adaptation in
      preterm infants using the electrical activity of the diaphragm (EAdi) signal.
      PATIENTS: Infants born between 28 + 0 and 31 + 6 gestational weeks and supported
      by early nasal continuous positive airway pressure (nCPAP) were studied. The EAdi
      signal was recorded for 120 min after birth. RESULTS: Eight preterm infants were
      evaluated. The median EAdi peak value of 19.2 MUV (lower quartile 13.1; upper
      quartile 22.2) at 20 min after birth decreased to 11.4 MUV (9.5-14.7) at 55 min
      of age. The median EAdi minimum value of 4.5 MUV (2.2-5.5) at 25 min after birth
      decreased to 1.6 MUV (1.2-2.7) at 85 min of age. CONCLUSION: EAdi was high right
      after birth. This indicates that preterm infants are capable of generating
      sufficient respiratory drive and diaphragm tone during expiration to establish
      and maintain functional residual capacity. Diaphragm activity decreased within
      the first 90 min, suggesting that early adaptation was accomplished by 90 min of
      age.

PMID- 30273720
TI  - Endovascular treatment of Vertebral-Venous Fistula with flow diverting stent: A
      Case Report.
AB  - BACKGROUND: Vertebral-venous fistulas (VVF) are a rare vascular condition and are
      commonly associated with trauma, but may also be idiopathic, spontaneous or
      congenital. A current literature review reveals there is no level 1 evidence or
      established guidelines on optimal treatment for VVF. Diagnosis is often confirmed
      by catheter cerebral angiogram. Treatment goals are complete occlusion of the
      fistula, which can be achieved by both endovascular closure and/or surgical
      ligation treatment. Telescopic Pipeline flow diversion stents are a common
      treatment modality for aneurysms and have also been described to successfully
      treat different types of cranial arteriovenous fistulas (AVF) including carotid
      cavernous fistulas (CCF).There is however no English literature available
      regarding its use in the management of vertebral-venous fistulas (VVF), which is
      a rare entity. CASE DESCRIPTION: The authors present a case of VVF, which is the
      first reported case to their knowledge whereby a Pipeline flow diverting stent
      has been used to successfully treat a VVF, whilst preserving the parent vertebral
      artery. The authors describe both the advantages and limitations of this
      approach. CONCLUSIONS: This case report highlights the potential of flow
      diversion stents in the treatment of VVF. This technique was shown to be a safe
      and effective method of treatment for VVF. Important limitations however need to
      be considered prior to this form of treatment for VVF, including the need for
      multiple devices, extended duration of treatment and associated increased costs
      involved.

PMID- 30273721
TI  - Intracranial Dural Parafalcine Chondroma: Case Report and Systematic Review of
      the Literature.
AB  - Intracranial chondromas are rare, benign neoplasms representing only 0.2%-0.3% of
      neoplastic intracranial lesions. They commonly originate from the skull base but
      can infrequently arise from the falx, convexity dura, or ventricular ependyma.
      Diagnosis requires histopathologic confirmation, as patients present with
      nonspecific symptoms related to mass effect, and imaging characteristics often
      resemble meningiomas, oligodendrogliomas, and vascular malformations. We describe
      the case of a patient harboring a parafalcine dural chondroma that was discovered
      incidentally and was managed surgically at our institution. We also provide a
      systematic review of the literature to elucidate incidence, origin, imaging
      findings, surgical management approaches, and prognosis of this rare tumor.

PMID- 30273722
TI  - Moderate Sedation for Pipeline Embolization of Posterior Circulation Disease:
      Technical Note from a Single Center.
AB  - OBJECTIVE: Flow diversion has been an important addition to endovascular
      neurosurgery, but its use in the posterior circulation remains controversial. Our
      goal is to describe the safety and efficacy of moderate sedation during flow
      diversion for posterior circulation lesions (aneurysms or dissecting
      pseudoaneurysms). METHODS: The authors retrospectively reviewed the medical
      records of all patients who underwent placement of a Pipeline embolization device
      for a posterior circulation lesion from August 2012 through November 2017.
      Clinical information and outcomes were evaluated. RESULTS: Fifteen consecutive
      patients were identified: 8 female, 7 male (mean age 52.2+/-16.3 years, range 15
      81). Eleven lesions were located in the vertebral artery, 1 in the posterior
      inferior cerebellar artery aneurysm, two in the posterior cerebral artery, and
      one in the basilar artery. All patients underwent flow diversion with Pipeline
      embolization devices. One patient experienced an acute occlusion of the basilar
      artery during the procedure that required revascularization. Mean fluoroscopy
      time was 35.6+/-16.5 minutes (range 15.5-75). Mean follow-up time was 12.7+/-8.8
      months (range 3-36). No patient had new neurological deficits in the
      perioperative or postoperative period. Conversion to general anesthesia was not
      required in any case. CONCLUSIONS: Moderate sedation is safe and feasible in
      patients undergoing flow diversion for posterior circulation lesions.
      Additionally, its use may allow for more rapid identification of procedural
      complications, facilitating emergent treatment and decreasing procedure-related
      morbidity.

PMID- 30273723
TI  - Sealing hyaluronic acid microgels with oppositely-charged polypeptides: A simple
      strategy for packaging hydrophilic drugs with on-demand release.
AB  - A simple route to deliver on demand hydrosoluble molecules such as peptides,
      packaged in biocompatible and biodegradable microgels, is presented. Hyaluronic
      acid hydrogel particles with a controlled structure are prepared using a
      microfluidic approach. Their porosity and their rigidity can be tuned by changing
      the crosslinking density. These negatively-charged polyelectrolytes interact
      strongly with positively-charged linear peptides such as poly-l-lysine (PLL).
      Their interactions induce microgel deswelling and inhibit microgel enzymatic
      degradability by hyaluronidase. While small PLL penetrate the whole volume of the
      microgel, PLL larger than the mesh size of the network remain confined at its
      periphery. They make a complexed layer with reduced pore size, which insulates
      the microgel inner core from the outer medium. Consequently, enzymatic
      degradation of the matrix is fully inhibited and non-affinity hydrophilic species
      can be trapped in the core. Indeed, negatively-charged or small neutral peptides,
      without interactions with the network, usually diffuse freely across the network.
      By simple addition of large PLL, they are packaged in the core and can be
      released on demand, upon introduction of an enzyme that degrades selectively the
      capping agent. Single polyelectrolyte layer appears as a simple generic method to
      coat hydrogel-based materials of various scales for encapsulation and controlled
      delivery of hydrosoluble molecules.

PMID- 30273724
TI  - Dual and multiple stimuli-responsive platonic micelles bearing disaccharides.
AB  - We recently identified completely monodisperse micelles whose aggregation number
      (Nagg) coincides with the vertex number of regular polyhedra, named Platonic
      micelles. The combination of both the micellar properties and controlling their
      structures by external stimuli could be promising for producing precisely
      controlled self-assembled structures. From this perspective, we newly synthesized
      a calix[4]arene-based amphiphile bearing disaccharides, cellobioses. The crowded
      and bulky structure in the hydrophilic group could provide a novel stimuli
      responsiveness of disaccharides in amphiphiles. The aggregation behavior such as
      the morphologies and the aggregation number of the calix[4]arene-based micelle
      was characterized using small angle scattering techniques and analytical
      ultracentrifugation measurements. Owing to hydrogen bonding among the
      disaccharide, the head volume became smaller than expected, resulting in the
      formation of cylindrical ones. However, cleaving the hydrogen bond by controlling
      temperature or pH induced morphological transition of the micellar structure from
      cylindrical to spherical. The dual-stimuli (temperature and pH) generated smaller
      micelles with Nagg of 12. Interestingly, when the amphiphile formed spherical
      micelles at various conditions, the Nagg matched the Platonic number, and the
      change of Nagg in response to the external stimuli was non-continuous, which is
      consistent with the concept of Platonic micelles.

PMID- 30273725
TI  - Association of fine particulate matter on acute exacerbation of chronic
      obstructive pulmonary disease in Yancheng, China.
AB  - BACKGROUND: Epidemiological evidence on the association between short-term
      exposure to fine particulate matter (PM2.5) air pollution and acute exacerbation
      of chronic obstructive pulmonary disease (AECOPD) is limited in China.
      OBJECTIVES: To explore the associations between PM2.5 and AECOPD in Yancheng,
      China from 2015 to 2017. METHODS: In this time-series study, we used a
      generalized linear model with quasi-Poisson regression to investigate the
      association between PM2.5 and AECOPD admitted in two major hospitals in Yancheng.
      We tested the robustness of the associations using two-pollutant models and
      examined the potential effect modification by age, gender and season via
      stratification analyses. Lastly, we fitted the concentration-response curves.
      RESULTS: We identified a total of 4761 AECOPD inpatients during the study period.
      The average daily-mean PM2.5 concentration was 45.2 MUg/m3. Each 10 MUg/m3
      increase in PM2.5 concentration on the concurrent day of the onset of AECOPD was
      associated with a 1.05% (95% confidence interval: 0.14%, 1.96%) increase in
      AECOPD. The association was robust to the adjustment of ozone, but not to sulfur
      dioxide, nitrogen dioxide, and carbon monoxide. The association was larger in
      females, elderly patients, and was restricted within the cold season, but all
      between-group differences were insignificant. The concentration-response
      relationship curves were generally linear but flatted at concentrations over 40
      MUg/m3. CONCLUSIONS: This study demonstrated a higher risk of AECOPD associated
      with present-day PM2.5 exposure in a Chinese city. We further provided important
      information on lag patterns, susceptible subgroups, sensitive seasons, as well as
      the characteristics of the concentration-response relationship curves.

PMID- 30273726
TI  - Acute and chronic effects of ambient fine particulate matter on preterm births in
      Beijing, China: A time-series model.
AB  - Accumulating evidence suggests that short- and long-term exposure to ambient fine
      particulate matter <= 2.5 MUm (PM2.5) during pregnancy is associated with preterm
      births, yet the results are inconsistent, and the shape of the exposure-response
      curve is unclear, partially due to the limited studies conducted in areas with
      high air pollution. Our study evaluated the association between ambient PM2.5
      concentration and preterm births in Beijing, China. Daily preterm birth data were
      collected from a hospital in Beijing during 2006 to 2013; a time-series of daily
      PM2.5 concentrations during the same period is assembled with measured data at
      three monitoring sites in Beijing. An extension of the Poisson regression and a
      time-series model were applied to simultaneously estimate the acute and chronic
      effects of exposure to PM2.5, with mutual adjustment for short- and long-term
      exposure as well as for confounders. During the study period, the PM2.5
      concentration was 70.4 +/- 60.6 MUg/m3 and was found to be associated with an
      increased risk of preterm birth. In the study cohort, a 0.52% (95% confidence
      interval, CI: 0.09%, 0.96%) and 3.13% (95%CI: 1.92%, 4.35%) increase in preterm
      births was estimated for each 10-MUg/m3 increase in short- and long-term
      exposure, respectively. This association was significantly modified by season (p
      < 0.05). With mutual adjustments for short- and long-term exposure, a more robust
      association (3.16%, 95% CI: 1.95%, 4.39%; per 10-MUg/m3 increment in PM2.5) was
      observed for chronic effects. The exposure-response relationships for both short-
      and long-term exposure were linear, without a threshold, over the relatively low
      exposure range and flattened out at higher concentration levels. The maximum
      effect for long-term exposure to PM2.5 (33.6%) was much greater than that for
      short-term exposure (19.9%). These findings indicate that air quality
      improvements over a long period could yield significant health benefits.

PMID- 30273727
TI  - Preparing coal slurry from coking wastewater to achieve resource utilization:
      Slurrying mechanism of coking wastewater-coal slurry.
AB  - Coking wastewater is used to prepare coal slurry, which can be used as combustion
      and gasification fuel. This promising technology simultaneously achieves resource
      utilization and wastewater management. Slurrying properties are essential to the
      industrial application of coal slurry. These properties are considerably
      influenced by coal surface properties and the adsorption of an additive by coal.
      In this study, the effects of the internal components (e.g., phenol, ammonia
      nitrogen, and metal ions) of coking wastewater on the adsorption of an additive
      by coal and on coal surface properties were measured. Results showed that the
      competitive adsorption between phenol and the additive reduced the amount of
      additive adsorbed on coal. However, phenol acted as an additive to improve the
      wettability of coal particles. Cations (Ca2+, NH4+, and Na+) adversely affected
      the slurrying because they weakened the negative charges of coal. Furthermore, a
      large amount of water was adsorbed due to the ionic bonding effects, thereby
      reducing the free water in the coal slurry system. The maximum slurrying
      concentration of CWCS was 0.8 percentage points higher than that of CWS,
      suggesting that coking wastewater enhanced the slurrying capability of the coal
      slurry by integrating the various effects induced by the different internal
      components.

PMID- 30273728
TI  - Ordered diatom species loss along a total phosphorus gradient in eutrophic lakes
      of the lower Yangtze River basin, China.
AB  - As global changes begin to affect the biosphere profoundly, the impacts on
      ecosystem health will become more significant. Understanding the sequence of
      functional species loss along an environmental or ecological gradient remains a
      research priority for ecosystem conservation. In this paper, nestedness, beta
      diversity and its components in diatom communities are used as ecological
      indicators of the dynamic change in functional species along environment
      gradients in 76 lakes of the lower Yangtze River basin, China. The results
      indicate that species turnover is typically the dominant component of beta
      diversity and that the influence of nestedness is generally low. However, changes
      in nestedness denote a significant threshold of lake eutrophication at a total
      phosphorus (TP) level of 0.06 mg/l, which is lower than the threshold indicated
      by diatom diversity. This finding was coupled with theoretical predictions about
      the successive proportional loss of 'canary' and 'keystone' species, which are
      replaced by 'weedy' species. These results show that nestedness of diatom
      communities can provide an additional metric for evaluating lake ecosystem health
      in this region. As management targets for nutrient control have already been
      introduced in the region, a revision of the identified critical phosphorus level
      (i.e., TP = 0.087-0.1 mg/l) to TP = 0.06 mg/l is proposed to keep lakes under low
      risk.

PMID- 30273729
TI  - Evaluation of the ecological protective effect of the "large basin" comprehensive
      management system in the Tarim River basin, China.
AB  - It is very important to construct a reasonable and efficient basin management
      system to meet the ecological water demand in arid areas with natural vegetation,
      and to maintain the integrity and stability of fragile ecosystems. However, how
      to assess the effect of basin management on ecological protection in arid areas
      as well as how to achieve the optimal control and efficient use of ecological
      water are major issues for many researchers and river basin managers. To address
      these two questions, we investigated the comprehensive management system for the
      Tarim River basin in China as a typical case study. The results showed that the
      natural vegetation coverage degree, the ecological water supply, temperature
      vegetation dryness index (TVDI), and the tree-ring chronology of Populus
      euphratica increased, whereas the disturbance of water resources by human
      activities decreased. Therefore, the effects of ecological protection were
      obvious after comprehensive "large basin" management. Based on an innovative
      application of tree-ring chronology to estimate the water leakage from the river,
      we determined the minimum runoff level (43.1 * 108 m3) when the natural
      vegetation needs to overflow. To further improve the effect of comprehensive
      management, the optimal regulation mode (i.e. maintaining the groundwater depth
      at 2-6 m, and the frequency and duration of overflowing at 2-3 times per year for
      a duration of 15-20 days during July to September) for the ecological sluices was
      formulated from the perspective of the efficient utilization of ecological water.
      These results provide a scientific reference for constructing reasonable
      management systems for similar river basins in arid areas.

PMID- 30273730
TI  - Using spatio-temporal fusion of Landsat-8 and MODIS data to derive phenology,
      biomass and yield estimates for corn and soybean.
AB  - The Simple Algorithm for Yield estimates (SAFY) is a crop yield model that
      simulates crop growth and biomass accumulation at a daily time step. Parameters
      in the SAFY model can be determined from literature, in situ measurements, or
      optical remote sensing data through data assimilation. For effective
      determination of parameters, optical remote sensing data need to be acquired at
      high spatial and high temporal resolutions. However, this is challenging due to
      interference of cloud cover and rather long revisiting cycles of high resolution
      satellite sensors. Spatio-temporal fusion of multi-source remote sensing data may
      represent a feasible solution. Here, crop phenology-related parameters in the
      SAFY model were derived using an improved Two-Step Filtering (TSF) model from
      remote sensing data generated through spatio-temporal fusion of Landsat-8 and
      Moderate Resolution Imaging Spectroradiometer (MODIS) data. Remaining parameters
      were determined through an optimization procedure using the same dataset. The
      SAFY model was then used for dry aboveground biomass and yield estimation at a
      subfield scale for corn (Zea mays) and soybean (Glycine max). The results show
      that the improved TSF method is able to determine crop phenology stages with an
      error of <5 days. After calibration, the SAFY model can reproduce daily Green
      Leaf Area Index (GLAI) effectively throughout the growing season and estimate
      crop biomass and yield accurately at a subfield scale using three Landsat-8 and
      10 MODIS images acquired for the season. This approach improves the accuracy of
      biomass estimation by about 4% in relative Root Mean Square Error (RRMSE),
      compared with the SAFY model without forcing the phenology-related parameters.
      The RMSE of yield estimation is 146.33 g/m2 for corn and 82.86 g/m2 for soybean.
      The proposed framework is applicable for local-scale or field-scale phenology
      detection and yield estimation.

PMID- 30273731
TI  - Manganese release linked to carbonate dissolution during the start-up phase of a
      subsurface iron removal well in Khabarovsk, Russia.
AB  - Subsurface iron removal (SIR) is a proven pre-treatment technology for removing
      dissolved iron and manganese from groundwater. The start-up phase of a SIR well
      and the proper development of the reaction zone around the well are crucial for
      its subsequent performance. This study evaluates the start-up phase of a SIR
      production well in Khabarovsk, Russia during the first 194 SIR cycles. A strong
      release of manganese was observed, which led to concentrations twice as high as
      the background value of the pristine groundwater. Regular monitoring of the
      production well and its three adjacent observation wells showed that iron removal
      began immediately after start-up and that the reaction zone was completely formed
      within 25 SIR cycles. Closed-bottle batch tests and a flow-through leaching test
      revealed that the grain size of the aquifer material and groundwater pH are the
      primary controls on manganese release. During infiltration phases the dissolution
      of manganese-bearing carbonate minerals was caused by direct oxidation by O2,
      whereas the low groundwater pH of 6 seemed to be responsible for the manganese
      release during extraction.

PMID- 30273732
TI  - Humboldt penguins' feathers as bioindicators of metal exposure.
AB  - Avian feathers have the potential to accumulate trace elements originating from
      contaminated food and polluted environments. In fact, in feathers, metals bind to
      keratin, a sulphur-containing protein for which several metals have a strong
      affinity. Here, the concentrations of 18 essential and non-essential elements
      were investigated in a Humboldt penguin (Spheniscus humboldti) colony housed at
      the Acquario di Cattolica (Italy). This species is listed as vulnerable in the
      Red List of the International Union for Conservation of Nature. According to the
      literature, there is usually a link between metal levels in the diet of birds and
      levels detected in their feathers. Thus, metals were also determined in the
      penguins' food (capelin, Mallotus villosus). We hypothesize that the controlled
      conditions in which birds are kept in captivity, and the homogeneous diet that
      they follow could allow a better understanding of metal bioaccumulation (such as
      mercury) or bio-dilution (such as arsenic) in the marine food chain, indicated by
      penguins' feathers. Moreover, comparisons with our previous investigations
      performed on an ex-situ African penguin (Spheniscus demersus) colony suggest that
      penguins living indoors have lower body burden of metals than those living
      outdoors. Indeed, environmental contaminants usually found in areas subjected to
      anthropogenic impact, where zoos and aquaria are often located, are not
      accumulated to levels of concern.

PMID- 30273733
TI  - Effects of urban growth spatial pattern (UGSP) on the land surface temperature
      (LST): A study in the Po Valley (Italy).
AB  - Sealed surfaces greatly influence Urban Heat Island (UHI) effects. In this
      respect, both the composition and spatial patterns of anthropogenic land use play
      an important role in local thermal pattern. The urban environments' climate
      change adaptation strategy needs adequate knowledge systems urban planners can
      use to organise and design more resistant and resilient urban spaces. This study
      examined the relationship between Land Surface Temperature (LST) variations and
      increasing urbanised areas during the period 2001-2011 in the Po Valley,
      utilising different urban growth spatial patterns (UGSP). Remotely sensed LST
      data was obtained from MODIS (MODerate Resolution Imaging Spectroradiometer) at a
      resolution of 1 km/pixel for an 11 year-period, from 2001 to 2011, with
      urbanisation data from the ISTAT map (nominal scale 1:10,000) respectively for
      the 2001 and 2011 time sections. The relationship between dependent (mean annual
      daytime, nighttime and daily values) and independent (urbanised areas) variables
      were investigated through ANOVA test and post-hoc analysis (p < 0.01) for all
      defined UGSP. Results showed that there is a decreasing LST range (in all
      conditions) associated with progressive increase of urbanised areas. Furthermore,
      clustered patterns urban growth have a statistically significant relationship
      with daytime, nighttime and daily conditions while dispersed pattern urban growth
      have the same with nighttime only. The outcomes are helpful for understanding the
      effects of different UGSP, which have significant implications for urban
      planning, and identifying the critical territorial sectors in need of sustainable
      mitigation actions.

PMID- 30273735
TI  - Anti-melanogenic effects of oyster hydrolysate in UVB-irradiated C57BL/6J mice
      and B16F10 melanoma cells via downregulation of cAMP signaling pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pacific oyster (Crassostrea gigas) has been used
      to treat pigmentary disorders such as freckles, melasma, and moles in Korea. AIM
      OF THE STUDY: We aimed to investigate the inhibitory effects of oyster
      hydrolysate (OH) on melanogenesis in B16F10 melanoma cells and UVB-irradiated
      C57BL/6J mice. MATERIAL AND METHODS: The molecular weight distribution and
      peptide sequences of OH were detected using MALDI-TOF and UHPLC. To evaluate the
      anti-melanogenic effects of OH, cell viability, melanin content, tyrosinase
      activity, intracellular cyclic adenosine monophosphate (cAMP) and protein
      expressions levels were measured in B16F10 cells. In addition, OH was orally
      administered to UVB-irradiated mice for 9 weeks. After sacrificing the mice, the
      whitening effects of OH were evaluated based on histological observations and
      protein expression levels. RESULTS: In B16F10 cells, OH decreased melanin content
      and tyrosinase activity in a dose-dependent manner. OH exhibited anti-melanogenic
      activities via downregulation of cAMP signaling pathway, which consequently
      decreased melanin synthesis. In UVB-irradiated mice groups, OH decreased the
      number of active melanocytes and melanin granules. The expression of tyrosinase
      related proteins and microphthalmia-associated transcription factor (MITF)
      decreased in the OH-administered groups. CONCLUSIONS: These results show that OH
      inhibits melanin synthesis in B16F10 cells via downregulation of cAMP signaling
      pathway and in UVB-irradiated mice, by decreasing the number of active
      melanocytes and melanin granules.

PMID- 30273709
TI  - Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change
      management in allergic rhinitis and asthma multimorbidity using mobile
      technology.
AB  - Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by
      using the best approach to integrated care pathways using mobile technology in
      patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next
      phase of ARIA is change management, with the aim of providing an active and
      healthy life to patients with rhinitis and to those with asthma multimorbidity
      across the lifecycle irrespective of their sex or socioeconomic status to reduce
      health and social inequities incurred by the disease. ARIA has followed the 8
      step model of Kotter to assess and implement the effect of rhinitis on asthma
      multimorbidity and to propose multimorbid guidelines. A second change management
      strategy is proposed by ARIA Phase 4 to increase self-medication and shared
      decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has
      been the development and validation of information technology evidence-based
      tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions
      on the basis of a self-care plan proposed by the health care professional.

PMID- 30273736
TI  - In vitro antiplasmodial, antitrypanosomal and antileishmanial activities of
      selected medicinal plants from Ugandan flora: Refocusing into multi-component
      potentials.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Seven medicinal plants from Ugandan flora, namely
      Entada abyssinica, Khaya anthotheca, Vernonia amygdalina, Baccharoides adoensis,
      Schkuhria pinnata, Entandropragma utile and Momordica foetida, were selected in
      this study. They are used to treat conditions and infections ranging from
      inflammations, pains and fevers to viruses, bacteria, protozoans and parasites.
      Two of the plants, V. amygdalina and M. foetida, are also used as human food or
      relish, while others are important in ethnoveterinary practices and in
      zoopharmacognosy in the wild. The aim of this study was to evaluate the in vitro
      antiplasmodial, antitrypanosomal and antileishmanial activities, along with
      cytotoxicity of the multi-component extracts of these plants. MATERIALS AND
      METHODS: Different parts of the plants were prepared and serially extracted with
      hexane, petroleum ether, dichloromethane, ethyl acetate, methanol and double
      distilled water. Solvent free extracts were assayed for in vitro inhibition
      against four reference parasite strains, Plasmodium falciparum (K1), Trypanosoma
      brucei rhodesiense (STIB 900), Trypanosoma cruzi (Talahuen C2C4) and Leishmania
      donovani (MHOM-ET-67/L82) using standard methods. Toxicity was assessed against
      L6 skeletal fibroblast and mouse peritoneal macrophage (J774) cells and
      selectivity indices (SIs) calculated for the most active extracts. RESULTS: The
      strongest activities, demonstrating median inhibitory concentration (IC50) values
      <= 2 MUg/ml, were observed for the dichloromethane and petroleum ether extracts
      of K. anthotheca, B. adoensis and S. pinnata. Overall, IC50 values ranged from <
      1 MUg/ml to > 90 MUg/ml. Out of 22 extracts demonstrating IC50s < 20 MUg/ml,
      seven were against T. b. rhodesiense (IC50: 1.6-16.2 MUg/ml), six against T.
      cruzi (IC50: 2.1-18.57 MUg/ml), none against L. donovani (IC50: falling > 3.3 and
      >10 MUg/ml), and nine against P. falciparum (IC50: 0.96 MUg/ml to 4.69 MUg/ml).
      Selectivity indices (SI) calculated for the most active extracts ranged from
      <1.00 to 94.24. However, the B. adoensis leaf dichloromethane extract (a) was
      equipotent (IC50 = 3.3 MUg/ml) against L. donovani and L6 cells respectively,
      indicating non-specific selection. Trypanosome and Plasmodium parasites were
      comparatively more sensitive to the test extracts. CONCLUSIONS: The benefits
      achieved from the seven tested plant species as traditional ethnomedicinal and
      ethnoveterinary therapies or in zoopharmacognosy against infections and
      conditions of animals in the wild are strongly supported by results of this
      study. The synergy of plant extracts, so achieved by concerted actions of the
      ligands, produces adequate perturbation of targets in the four parasite genera,
      resulting in the strong potencies exhibited by low IC50 values. The total
      inhibitory effect, achieved as a sum of perturbations contributed by each
      participating compound in the extract, minimises toxic effects of the compounds
      as seen in the high SI's obtained with some extracts. Those extracts
      demonstrating SI >= 4 form promising candidates for further cell-based and system
      pharmacology studies.

PMID- 30273734
TI  - Environmental concentrations of triclosan activate cellular defence mechanism and
      generate cytotoxicity on zebrafish (Danio rerio) embryos.
AB  - Triclosan (TCS, 5-chloro-2-(2,4-dichlorophenoxy) phenol) is becoming a major
      surface waters pollutant worldwide at concentrations ranging from ng L-1 to MUg L
      1. Up to now, the adverse effects on aquatic organisms have been investigated at
      concentrations higher than the environmental ones, and the pathways underlying
      the observed toxicity are still not completely understood. Therefore, the aim of
      this study was to investigate the toxic effects of TCS at environmental
      concentrations on zebrafish embryos up to 120 hours post fertilization (hpf). The
      experimental design was planned considering both the quantity and the exposure
      time for the effects on the embryos, exposing them to two different
      concentrations (0.1 MUg L-1, 1 MUg L-1) of TCS, for 24 h (from 96 to 120 hpf) and
      for 120 h (from 0 to 120 hpf). A suite of biomarkers was applied to measure the
      induction of embryos defence system, the possible increase of oxidative stress
      and the DNA damage. We measured the activity of glutathione-S-transferase (GST),
      P-glycoprotein efflux and ethoxyresorufin-o-deethylase (EROD), the level of ROS,
      the oxidative damage through the Protein Carbonyl Content (PCC) and the activity
      of antioxidant enzymes. The genetic damage was evaluated through DNA Diffusion
      Assay, Micronucleus test (MN test), and Comet test. The results showed a clear
      response of embryos defence mechanism, through the induction of P-gp efflux
      functionality and the activity of detoxifying/antioxidant enzymes, preventing the
      onset of oxidative damage. Moreover, the significant increase of cell necrosis
      highlighted a strong cytotoxic potential for TCS. The overall results obtained
      with environmental concentrations and both exposure time, underline the critical
      risk associated to the presence of TCS in the aquatic environment.

PMID- 30273737
TI  - A fast and reliable protocol for activation of porcine oocytes.
AB  - Oocyte activation is physiologically triggered by the sperm during fertilization,
      however, production of porcine embryos by somatic cell nuclear transfer (SCNT),
      intracytoplasmic sperm injection (ICSI) or parthenogenetic activation (PA)
      requires artificial oocyte activation. Although effective protocols for
      artificial oocyte activation have been developed, current protocols require long
      exposures to non-specific inhibitors, which do not mimic the physiological
      process and may have detrimental consequences for embryo development. This study
      attempted to mimic the physiological activation events induced by fertilization,
      through the manipulation of Ca2+ and Zn2+ levels, and protein kinase C (PKC) as
      well as cyclin dependent kinase 1 (CDK1) activities, with the aim of developing
      an improved protocol for activation of porcine oocytes. In the first experiment,
      matured oocytes were exposed to ionomycin (Ion) for 5 min, and then treated with
      a specific CDK1 inhibitor (RO-3306) and/or PKC activator (OAG) for different time
      intervals. The highest rate of pronuclear (PN) formation (58.8%) was obtained
      when oocytes were treated with PKCa + CDK1i for 4 h. Second, PN formation and
      embryo development were evaluated in oocytes exposed for different times to a
      Zn2+ chelator (TPEN) following Ion treatment. This revealed that 15 min was the
      minimal exposure time to TPEN required to maximise oocyte activation and embryo
      development. Next, we observed that treatment with PKCa + CDK1i for 4 h after
      TPEN for 15 min decreased embryo development compared to TPEN alone. Lastly, we
      compared the efficiency of the Ion (5 min) plus TPEN (15 min) protocol (IT-20)
      with a control protocol used in our laboratory (CT-245) for production of PA,
      SCNT and ICSI embryos. In PA embryos, IT-20 resulted in higher cleavage (72% vs
      49.2%) and blastocyst from cleaved embryos (65.5% vs 46.2%) compared to CT-245.
      In ICSI embryos, higher PN rates were obtained with the IT-20 protocol compared
      with CT-245 and the non-activated (N-A) group. Moreover, the two protocols were
      equally efficient for activation of SCNT embryos. Based on these findings, we
      propose that IT-20 is a fast and effective protocol for activation of porcine
      oocytes.

PMID- 30273739
TI  - Effect of the hematopoietic growth factors erythropoietin and kit ligand on
      bovine oocyte in vitro maturation and developmental competence.
AB  - The overall aim of this work was to study the influence of the hematopoietic
      growth factors erythropoietin (EPO) and kit ligand (KITL) during bovine oocyte in
      vitro maturation (IVM). The effect of adding different concentrations of EPO or
      KITL to maturation medium was evaluated analyzing oocyte nuclear maturation,
      cumulus cells apoptosis, embryo cleavage, reactive oxygen species (ROS)
      production in matured oocytes and cleaved embryos and the developmental
      competence to the blastocyst stage. No significant differences were observed in
      the percentage of oocytes that completed nuclear maturation among treatments, but
      the percentages of cleaved embryos and blastocysts obtained increased. With the
      addition of both hematopoietic growth factors the percentage of cumulus cells
      undergoing apoptosis decreased, the number of blastomeres per cleaved embryo was
      larger and ROS production per cleaved embryo increased. In conclusion, although
      the addition of EPO and KITL hematopoietic growth factors during bovine oocyte
      IVM had no impact on nuclear maturation, it had a positive effect on oocyte
      cytoplasmic maturation and developmental competence.

PMID- 30273740
TI  - Hydration-induced nano- to micro-scale self-recovery of the tooth enamel of the
      giant panda.
AB  - The tooth enamel of vertebrates comprises a hyper-mineralized bioceramic, but is
      distinguished by an exceptional durability to resist impact and wear throughout
      the lifetime of organisms; however, enamels exhibit a low resistance to the
      initiation of large-scale cracks comparable to that of geological minerals based
      on fracture mechanics. Here we reveal that the tooth enamel, specifically from
      the giant panda, is capable of developing durability through counteracting the
      early stage of damage by partially recovering its innate geometry and structure
      at nano- to micro- length-scales autonomously. Such an attribute results
      essentially from the unique architecture of tooth enamel, specifically the
      vertical alignment of nano-scale mineral fibers and micro-scale prisms within a
      water-responsive organic-rich matrix, and can lead to a decrease in the dimension
      of indent damage in enamel introduced by indentation. Hydration plays an
      effective role in promoting the recovery process and improving the indentation
      fracture toughness of enamel (by ~73%), at a minor cost of micro-hardness (by
      ~5%), as compared to the dehydrated state. The nano-scale mechanisms that are
      responsible for the recovery deformation, specifically the reorientation and
      rearrangement of mineral fragments and the inter- and intra-prismatic sliding
      between constituents that are closely related to the viscoelasticity of organic
      matrix, are examined and analyzed with respect to the structure of tooth enamel.
      Our study sheds new light on the strategies underlying Nature's design of durable
      ceramics which could be translated into man-made systems in developing high
      performance ceramic materials. STATEMENT OF SIGNIFICANCE: Tooth enamel plays a
      critical role in the function of teeth by providing a hard surface layer to
      resist wear/impact throughout the lifetime of organisms; however, such enamel
      exhibits a remarkably low resistance to the initiation of large-scale cracks, of
      hundreds of micrometers or more, comparable to that of geological minerals. Here
      we reveal that tooth enamel, specifically that of the giant panda, is capable of
      partially recovering its geometry and structure to counteract the early stages of
      damage at nano- to micro-scale dimensions autonomously. Such an attribute results
      essentially from the architecture of enamel but is markedly enhanced by
      hydration. Our work discerns a series of mechanisms that lead to the deformation
      and recovery of enamel and identifies a unique source of durability in the enamel
      to accomplish this function. The ingenious design of tooth enamel may inspire the
      development of new durable ceramic materials in man-made systems.

PMID- 30273738
TI  - The effects of crocetin supplementation on the blastocyst outcome, transcriptomic
      and metabolic profile of in vitro produced bovine embryos.
AB  - The earliest stages of embryo development are deeply influenced by reactive
      oxygen species (ROS), byproducts of the mitochondrial oxygen metabolism that play
      a key role as messengers in normal cell signal transduction and cell cycling.
      Despite its positive roles, the imbalance caused by the excess of ROS and an
      inefficient antioxidant system leads to oxidative stress, with negative
      consequences to the cell such as DNA damage, metabolic changes, mitochondrial
      stress and cell death. In the present work, crocetin - a natural antioxidant -
      was added to the culture media of bovine embryos to evaluate the efficiency of
      its antioxidant capability during embryo culture. Oocytes were in vitro matured
      (IVM) and fertilized according to standard protocols. Embryos were cultured at
      38.5  degrees C under humidified air with 5% CO2, 7% O2, and 90% N2 in Synthetic
      Oviduct Fluid (SOF) medium supplemented with amino acids and either 5% of FBS
      (SOFaa) (control group) or SOFaa supplemented with 1  MUM crocetin (crocetin
      group). After 5 days from the beginning of in vitro culture (IVC) (day 5 - D5),
      embryos were transferred to individual drops of culture media. At day 7 (D7),
      embryos were assessed by means of blastocyst rates, morphophysiological analyzes
      (total cell number, ROS and mitochondrial activity levels), transcript
      quantitation of 47 genes and metabolomic evaluation of the culture media by Raman
      spectroscopy. In the crocetin group blastocyst rates were higher and embryos had
      increased total cell number and decreased intracellular levels of ROS. These
      embryos also had upregulation of genes related with response to stress and lipid
      metabolism (ATF4, BAX, FOXO3, GADD45A, GPX1, GPX4, HSF1, SOD2, ACACA, SREBF1 and
      SREBF2). Raman spectroscopy corroborated these results indicating more active
      lipid and amino acid production in this group. The absence of crocetin in the
      culture media resulted in higher ROS level, as well as up regulation of genes
      related to DNA damage, stress response and energy metabolism (MORF4L2, SOD1, TXN,
      PFKP, PGK1 and PPARGC1A). In conclusion, crocetin supplementation during culture
      protects embryos from oxidative stress and influences the adaptive response to
      stress conditions, leading to an increase in both blastocyst yield and quality,
      as well as changes in transcriptomic and metabolic profile of in vitro produced
      bovine embryos.

PMID- 30273741
TI  - Mechanically stimulated osteochondral organ culture for evaluation of
      biomaterials in cartilage repair studies.
AB  - Surgical procedures such as microfracture or autologous chondrocyte implantation
      have been used to treat articular cartilage lesions; however, repair often fails
      in terms of matrix organization and mechanical behaviour. Advanced biomaterials
      and tissue engineered constructs have been developed to improve cartilage repair;
      nevertheless, their clinical translation has been hampered by the lack of
      reliable in vitro models suitable for pre-clinical screening of new implants and
      compounds. In this study, an osteochondral defect model in a bioreactor that
      mimics the multi-axial motion of an articulating joint, was developed.
      Osteochondral explants were obtained from bovine stifle joints, and cartilage
      defects of 4 mm diameter were created. The explants were used as an interface
      against a ceramic ball applying dynamic compressive and shear loading.
      Osteochondral defects were filled with chondrocytes-seeded fibrin-polyurethane
      constructs and subjected to mechanical stimulation. Cartilage viability,
      proteoglycan accumulation and gene expression of seeded chondrocytes were
      compared to free swelling controls. Cells within both cartilage and bone remained
      viable throughout the 10-day culture period. Loading did not wear the cartilage,
      as indicated by histological evaluation and glycosaminoglycan release. The gene
      expression of seeded chondrocytes indicated a chondrogenic response to the
      mechanical stimulation. Proteoglycan 4 and cartilage oligomeric matrix protein
      were markedly increased, while mRNA ratios of collagen type II to type I and
      aggrecan to versican were also enhanced. This mechanically stimulated
      osteochondral defect culture model provides a viable microenvironment and will be
      a useful pre-clinical tool to screen new biomaterials and biological regenerative
      therapies under relevant complex mechanical stimuli. STATEMENT OF SIGNIFICANCE:
      Articular cartilage lesions have a poor healing capacity and reflect one of the
      most challenging problems in orthopedic clinical practice. The aim of current
      research is to develop a testing system to assess biomaterials for implants, that
      can permanently replace damaged cartilage with the original hyaline structure and
      can withstand the mechanical forces long term. Here, we present an osteochondral
      ex vivo culture model within a cartilage bioreactor, which mimics the complex
      motion of an articulating joint in vivo. The implementation of mechanical forces
      is essential for pre-clinical testing of novel technologies in the field of
      cartilage repair, biomaterial engineering and regenerative medicine. Our model
      provides a unique opportunity to investigate healing of articular cartilage
      defects in a physiological joint-like environment.

PMID- 30273742
TI  - Mesoporous bioactive glasses: Promising platforms for antibacterial strategies.
AB  - The control of bacterial infections is of particular importance in the field of
      tissue engineering. Recently, much attention has been addressed toward the use of
      mesoporous bioactive glasses (MBGs) for antibacterial strategies, primarily
      because of their capability of acting as carriers for the local release of
      antimicrobial agents. The incorporation of antibacterial metallic ions including
      silver (Ag+), zinc (Zn2+), copper (Cu+ and Cu2+), cerium (Ce3+ and Ce4+), and
      gallium (Ga3+) cations into the MBG structure and their controlled release is
      proposed as one of the most attractive strategies for inhibiting bacterial growth
      and reproduction. Moreover, the possibility of loading and delivering various
      antibacterial biomolecules (e.g., antibiotics) through the porous structure of
      MBGs makes them as ideal candidates for antibacterial applications. In this
      review, we aim to present a comprehensive evaluation of MBG potential regarding
      antibacterial activities. For this purpose, different types of antibacterial ion
      doped and drug-loaded MBGs are introduced and discussed in the light of existing
      knowledge, along with the significant challenges ahead. STATEMENT OF
      SIGNIFICANCE: Prevention and treatment of infections is one of the today's
      greatest challenges in medical sciences, also considering the well-known issues
      related to increased bacterial resistance to antibiotics. The advent of
      mesoporous glasses led to the birth of a new class of multifunctional
      biomaterials acting as bioactive platforms for the local release of organic or
      inorganic agents eliciting an antimicrobial effect. This reviews summarizes the
      state of the art of MBGs in this field, highlighting the latest evolutions and
      the specific role played by metallic antimicrobial ions that can be incorporated
      in the glass composition and then properly released. Perspective for tissue
      engineering applications are also discussed to provide an up-to-date contribution
      that is useful to both experienced scientists and early-stage researchers.

PMID- 30273743
TI  - Graphene oxide induces p62/SQSTM-dependent apoptosis through the impairment of
      autophagic flux and lysosomal dysfunction in PC12 cells.
AB  - Graphene oxide (GO), as a two-dimensional carbon nanosheet, has been extensively
      studied for potential biomedical applications due to its notable properties.
      Although a growing number of studies have investigated the adverse effects of GO
      nanosheets, the available toxicity data concerning GO's effect on the neuronal
      cells remain highly limited. In this work, we systematically investigated the
      toxic responses of commercially available GO on a rat pheochromocytoma-derived
      PC12 cell line, which was an ideal in vitro model to study the neurotoxicity of
      GO. GO exerted a significant toxic effect on PC12 cells in a dose- and time
      dependent manner. GO treatments under doses of 40, 50, and 60 MUg/mL triggered an
      autophagic response and the blockade of autophagic flux via disrupting lysosome
      degradation capability. Caspase 9-mediated apoptosis was also observed in GO
      treated cells. Moreover, GO-induced apoptosis was relevant to the aberrant
      accumulation of autophagy substrate p62/SQSTM. Inhibitionofthe accumulation of
      autophagic substrate alleviated GO-caused apoptotic cell death. Our findings
      raise a concern for the putative biomedical applications of GO in the form of
      diagnostic and therapeutic tools, where its systematic biocompatibility should be
      thoroughly explored. STATEMENT OF SIGNIFICANCE: Graphene oxide (GO) has attracted
      considerable interests in biomedical fields, which also resulted in numerous
      safety risks to human bodies. It is urgently required to establish a paradigm for
      accurately evaluating their adverse effects in biological systems. This study
      thoroughly explored the neurotoxicity of GO in PC12 cells. We found GO triggered
      an increased autophagic response and the impairment of autophagic flux, which was
      functionally involved in cell apoptosis. Inhibitionofexcessive accumulation of
      autophagic cargo attenuated apoptotic cell death. Our findings highlight deep
      considerations on the regulation mechanism of autophagy-lysosomes-apotosis-axis,
      which will contribute to a better understanding of the neurotoxicity of graphene
      family nanomaterials, and provide a new insight in the treatment of cancer cells
      at nanoscale levels.

PMID- 30273744
TI  - Correlating diameter, mechanical and structural properties of poly(l-lactide)
      fibres from needleless electrospinning.
AB  - The development and application of nanofibres requires a thorough understanding
      of the mechanical properties on a single fibre level including respective
      modelling tools for precise fibre analysis. This work presents a mechanical and
      morphological study of poly-l-lactide nanofibres developed by needleless
      electrospinning. Atomic force microscopy (AFM) and micromechanical testing (MMT)
      were used to characterise the mechanical response of the fibres within a diameter
      range of 200-1400 nm. Young's moduli E determined by means of both methods are in
      sound agreement and show a strong increase for thinner fibres below a critical
      diameter of 800 nm. Similar increasing trends for yield stress and hardening
      modulus were measured by MMT. Finite element analyses show that the common
      practice of modelling three-point bending tests with either double supported or
      double clamped beams is prone to significant bias in the determined elastic
      properties, and that the latter is a good approximation only for small diameters.
      Therefore, an analytical formula based on intermediate boundary conditions is
      proposed that is valid for the whole tested range of fibre diameters, providing a
      consistently low error in axial Young's modulus below 10%. The analysis of fibre
      morphology by differential scanning calorimetry and 2D wide-angle X-ray
      scattering revealed increasing polymer chains alignment in the amorphous phase
      and higher crystallinity of fibres for decreasing diameter. The combination of
      these observations with the mechanical characterisation suggests a linear
      relationship between Young's modulus and both crystallinity and molecular
      orientation in the amorphous phase. STATEMENT OF SIGNIFICANCE: Fibrous membranes
      have rapidly growing use in various applications, each of which comes with
      specific property requirements. However, the development and production of
      nanofibre membranes with dedicated mechanical properties is challenging, in
      particular with techniques suitable for industrial scales such as needleless
      electrospinning. It is therefore a key step to understand the mechanical and
      structural characteristics of single nanofibres developed in this process, and to
      this end, the present work presents changes of internal fibre structure and
      mechanical properties with diameter, based on dedicated models. Special attention
      was given to the commonly used models for analyzing Young's modulus of single
      nanofibers in three-point bending tests, which are shown to be prone to large
      errors, and an improved robust approach is proposed.

PMID- 30273745
TI  - Antimicrobial activity of commercial calcium phosphate based materials
      functionalized with vanillin.
AB  - Infections represent one of the most frequent causes of arthroplasty revision.
      Thus, design of new antimicrobial scaffolds to reduce implant rejections, bone
      infections and associated medical costs is highly desired. In recent years,
      essential oil components (EOCs) have merged as compounds with significant
      antimicrobial activity that can be attached to specific surfaces to enhance and
      prolong their antimicrobial effect. Herein calcium phosphate CaP regenerative
      materials have been coated with a vanillin derivative to combine its original
      bone regeneration properties with antimicrobial action of EOCs. Materials in form
      of microparticles and blocks were prepared and fully characterized. Clonogenic
      viability tests demonstrated that low concentrations of material (10 mg.mL-1)
      resulted effective to kill 100% of E. coli DH5alpha bacteria. Additionally,
      vanillin containing scaffolds did not display any toxic effect over cells, yet
      they preserve the ability to express alkaline phosphatase (ALPL), collagen type
      1, chain alpha1 (COL1A1) and bone gamma-carboxyglutamic acid-containing protein
      or osteocalcin (BGLAP), which are genes typically expressed by osteoblasts. These
      results demonstrate that commercially available scaffolds can be functionalized
      with EOCs, achieving antimicrobial activity and open up a new approach for the
      treatment and prevention of infection. STATEMENT OF SIGNIFICANCE: During the last
      years, the interest in bone regenerative materials with antibiotic properties has
      increased, since prosthesis infection is one of the most usual complications in
      implant surgery. In this work, we report a hybrid system composed by a calcium
      phosphate material (powders and scaffolds) functionalized with the derivative of
      an essential oil component (EOC). Our purpose was to provide the calcium
      phosphate material with antimicrobial activity without harming its bone
      regenerative capability. The obtained results were encouraging, which opens up
      the possibility of developing new modified materials for the prevention and
      treatment of bone infection.

PMID- 30273746
TI  - Bactericidal effects of nanopatterns: A systematic review.
AB  - : We systematically reviewed the currently available evidence on how the design
      parameters of surface nanopatterns (e.g. height, diameter, and interspacing)
      relate to their bactericidal behavior. The systematic search of the literature
      resulted in 46 studies that satisfied the inclusion criteria of examining the
      bactericidal behavior of nanopatterns with known design parameters in absence of
      antibacterial agents. Twelve of the included studies also assessed the
      cytocompatibility of the nanopatterns. Natural and synthetic nanopatterns with a
      wide range of design parameters were reported in the included studies to exhibit
      bactericidal behavior. However, most design parameters were in the following
      ranges: heights of 100-1000 nm, diameters of 10-300 nm, and interspacings of 
      <500 nm. The most commonly used type of nanopatterns were nanopillars, which
      could kill bacteria in the following range of design parameters: heights of 100
      900 nm, diameters of 20-207 nm, and interspacings of 9-380 nm. The vast majority
      of the cytocompatibility studies (11 out of 12) showed no adverse effects of
      bactericidal nanopatterns with the only exception being nanopatterns with
      extremely high aspect ratios. The paper concludes with a discussion on the
      evidence available in the literature regarding the killing mechanisms of
      nanopatterns and the effects of other parameters including surface affinity of
      bacteria, cell size, and extracellular polymeric substance (EPS) on the killing
      efficiency. STATEMENT OF SIGNIFICANCE: The use of nanopatterns to kill bacteria
      without the need for antibiotics represents a rapidly growing area of research.
      However, the optimum design parameters to maximize the bactericidal behavior of
      such physical features need to be fully identified. The present manuscript
      provides a systematic review of the bactericidal nanopatterned surfaces.
      Identifying the effective range of dimensions in terms of height, diameter, and
      interspacings, as well as covering their impact on mammalian cells, has enabled a
      comprehensive discussion including the bactericidal mechanisms and the factors
      controlling the bactericidal efficiency. Overall, this review helps the readers
      have a better understanding of the state-of-the-art in the design of bactericidal
      nanopatterns, serving as a design guideline and contributing to the design of
      future experimental studies.

PMID- 30273747
TI  - Peroxidase-immobilized porous silica particles for in situ formation of
      peroxidase-free hydrogels with attenuated immune responses.
AB  - Enzymatic crosslinking chemistry using horseradish peroxidase (HRP) has been
      widely utilized as an effective approach to fabricating injectable hydrogels with
      high efficiency under mild reaction conditions. However, their clinical
      applications are limited by the immunogenicity of the plant-derived enzyme.
      Herein we report the design, synthesis and characterization of HRP-immobilized
      porous silica particles (HRP-particles) and their use for in situ formation of
      HRP-free hydrogels. HRP was immobilized on aminopropyl-modified porous silica
      particles of 70-140 um in diameter via poly(ethylene glycol) spacers of different
      molecular weights by reductive amination reaction. Two different HRP-free
      hydrogels based on dextran-tyramine and gelatin-hydroxyphenylpropionic acid
      (GHPA) conjugates were produced by passing a solution containing the conjugates
      and H2O2 through a syringe packed with HRP-particles. The storage modulus and
      gelation rate of both hydrogels were tunable by varying the contact time between
      the polymer solution and HRP-particles. Our in vitro study revealed that HRP-free
      GHPA hydrogel was less stimulatory to activated mouse macrophages than HRP
      containing GHPA hydrogel with the same stiffness. Furthermore, HRP-free GHPA
      hydrogel exhibited remarkably lower levels of local and systemic inflammation
      than HRP-containing one upon subcutaneous injection in immunocompetent C57BL/6J
      mice. The attenuated immunogenicity of HRP-free GHPA hydrogels makes them an
      attractive platform for tissue engineering applications. STATEMENT OF
      SIGNIFICANCE: The immunogenicity of HRP is a significant issue for clinical
      application of HRP-catalyzed in situ forming hydrogels. HRP-particles are
      developed to overcome the safety concerns by fabricating HRP-free hydrogels. The
      porosity of silica particles and molecular weight of poly(ethylene glycol)
      spacers are discovered as important factors determining the catalytic ability of
      HRP-particles to induce the in situ crosslinking of polymer-phenol conjugates.
      Although several articles speculate the potential of HRP to trigger immune
      responses when administered as a part of hydrogel formulation, no literature has
      attempted to investigate the immunogenicity of HRP-containing hydrogels in
      comparison with HRP-free hydrogels. Our findings suggest that the immunogenicity
      issue should be carefully considered before clinical translation of HRP
      containing hydrogels.

PMID- 30273748
TI  - The inflammasome in host response to biomaterials: Bridging inflammation and
      tissue regeneration.
AB  - : The development of new biomaterials to be used in tissue engineering
      applications is creating new solutions for a range of healthcare problems. The
      trend in biomaterials research has shifted from biocompatible "immune-evasive"
      biomaterials to "immune-interactive" materials that modulate the inflammatory
      response supporting implant integration as well as improving healing and tissue
      regeneration. Inflammasomes are large intracellular multiprotein complexes that
      are key players in host defence during innate immune responses and assemble after
      recognition of pathogens or danger signals. The process of biomaterial
      implantation causes injury to tissues that will consequently release danger
      signals that could be sensed by the inflammasome. There are increasing evidences
      that the inflammasome has a role in several inflammatory processes, from pathogen
      clearance to chronic inflammation or tissue repair. Thus, modulation of the
      inflammasome activity appears as an important target in the development of
      effective approaches in regenerative medicine. In this review, we discuss the
      main points of the current understanding on the host response to implanted
      biomaterials and how the paradigm of "immune-evasive" biomaterials has shifted
      over the last years; the significance of the inflammasome in the inflammatory
      response to biomaterials; and the growing idea that the immune system is of key
      importance in an effective tissue repair and regeneration. STATEMENT OF
      SIGNIFICANCE: We herein discuss the main points of the current understanding on
      the host response to implanted biomaterials and how the paradigm of "immune
      evasive" biomaterials has shifted to "immune-interactive" over the last years;
      the significance of the inflammasome in the inflammatory response to
      biomaterials; and the growing idea that the immune system is of key importance in
      an effective tissue repair and regeneration, supporting the emerging concept of
      Regenerative Immunology. The inflammasome is a recent and central concept in
      immunology research. Since the beginning of this century the inflammasome is
      viewed as key platform of the innate immune response. We believe that, successful
      modulation of the inflammasome activity will become a milestone in the fields of
      tissue engineering and regenerative medicine.

PMID- 30273749
TI  - Side effects-avoided theranostics achieved by biodegradable magnetic silica
      sealed mesoporous polymer-drug with ultralow leakage.
AB  - The development of drug delivery vehicles without side effects to normal
      physiological tissues represents an urgent challenge for safety and effective
      nanomedicine. Herein, a multifunctional drug delivery vehicle with ultralow
      leakage was presented, containing an ordered mesoporous resin as a polymer core
      and homogeneous Fe nanodots-doped silica as the biodegradable shell. In this core
      shell structure, the Fe-doped silica shell acts as a compact inorganic cap to
      seal doxorubicin into the mesoporous polymer cores, but also serves as a
      superparamagnetic agent for magnetic targeting and magnetic resonance imaging
      (MRI). Importantly, the caps can be opened via Fe extraction-induced degradation
      to slowly release the loaded drug under the acidic tumor environment, while
      achieving ultralow drug leakage under normal in vivo blood circulation
      (physiological environment). This unique core-shell nanospheres with ultralow
      drug leakage were demonstrated to achieve side effects-avoided targeting
      chemotherapy guided by MRI with improved therapeutic outcomes, which showing
      great potential for efficient cancer theranostics.

PMID- 30273750
TI  - Gastric Obstruction Secondary to an Unexplained Hyperinflation of an Intragastric
      Balloon.

PMID- 30273751
TI  - AGA Clinical Practice Update: Surgical Risk Assessment and Perioperative
      Management in Cirrhosis.

PMID- 30273752
TI  - Intramural Diverticulosis of the Bile Duct System.

PMID- 30273753
TI  - Maintaining performance in searching dogs: Evidence from a rat model that
      training to detect a second (irrelevant) stimulus can maintain search and
      detection responding.
AB  - Scent-detecting dogs perform a sequence, or chain, of behaviors that, at minimum,
      includes searching followed by a detection behavior that signals the presence of
      a target stimulus to the handler. However, when working, dogs often engage in
      prolonged periods of searching without encountering a target. It is therefore
      important for trainers to use methods that promote persistent search behavior and
      target detection accuracy. Laboratory models can provide insights to the
      important variables that influence search persistence and accuracy. The present
      experiments examined a rat model of detection dog behavior. Two experiments
      assessed the use of practice with a single target stimulus to maintain search and
      detection of another previously-trained target. In Experiment 1, after learning a
      search->detection chain with two auditory targets, rats received either brief or
      extended training with only one of the targets before being tested for detection
      of both targets in extinction. The results suggest that single-target training
      strengthened the ability of the other target to control the detection behavior.
      Experiment 2 found that even infrequent target encounters were still effective at
      maintaining detection behavior to the other trained target. Importantly, the
      treatment was effective when the target stimuli were from different sensory
      modalities. Overall, the results support the utility of the rat model of search
      dog behavior for evaluating novel training methods. We suggest several useful
      procedures for enhancing search persistence and accuracy in detection dogs that
      can be implemented in training protocols.

PMID- 30273754
TI  - Predator avoidance training of the endangered lizard from El Hierro (Canary
      Islands): A new management strategy before reintroduction into the wild.
AB  - Animals raised in captivity during several generations may not express
      appropriate antipredator behaviour when reintroduced into the wild. Here we
      present the results of experiments to enhance behavioural responses to predators
      in adult males of the endangered lizard Gallotia simonyi (El Hierro, Canary
      Islands). Individuals were subjected to a training procedure (control, pre
      training, training and post-training phases) using stuffed specimens of a kestrel
      and a cat as predators. We filmed all trials and compared relative durations of
      the more common behaviour patterns shown by lizards, both among experimental
      phases and before and after presentation of the stuffed predator. Locomotion and
      Basking were significantly reduced in the training and post-training trials and
      also after stimulus presentation, suggesting that the training protocol induced
      lizard avoidance over both predator models. To our knowledge, this is the first
      time lizards have been trained to show antipredator avoidance and our results
      provide the basis for a new management strategy that could be useful for
      reintroduction of captive-bred individuals of endangered species.

PMID- 30273755
TI  - Preference in female laboratory mice is influenced by social experience.
AB  - Mice must perceive and interpret the signals they are presented with to evaluate
      potential mates, and should show a preference for high quality conspecifics. The
      present experiment was designed to investigate preference for acoustic,
      olfactory, and acoustic + olfactory signals in laboratory mice. Eighteen female
      CBA/CaJ mice, socially housed or isolated, were tested to evaluate preference for
      signals produced by males. Social experience influenced female preference for
      male USV playback and soiled bedding. Female mice who had experience with males
      showed a stronger preference for olfactory signals, whereas female mice with
      experience only with other females preferred USV playback. Isolated mice showed a
      greater preference for signals of different modalities presented together than
      socially experienced mice. This preference may have occurred because of increased
      motivation to make social contact. The findings of this experiment illustrate
      that social experience could play a role in mate choice.

PMID- 30273756
TI  - High extinction rates and non-adaptive radiation explains patterns of low
      diversity and extreme morphological disparity in North American blister beetles
      (Coleoptera, Meloidae).
AB  - Untangling the relationship between morphological evolution and lineage
      diversification is key to explain global patterns of phenotypic disparity across
      the Tree of Life. Few studies have examined the relationship between high
      morphological disparity and extinction. In this study, we infer phylogenetic
      relationships and lineage divergence times within Eupomphini (Meloidae), a tribe
      of blister beetles endemic to the arid zone of North America, which exhibits a
      puzzling pattern of very low species richness but wild variation in morphological
      diversity across extant taxa. Using Bayesian and maximum likelihood inference, we
      estimate diversification and phenotypic evolutionary rates and infer the time and
      magnitude of extinction rate shifts and mass extinction events. Our results
      suggest that Eupomphini underwent an event of ancient radiation coupled with
      rapid morphological change, possibly linked to the loss of the evolutionary
      constraint in the elytral shape. A high extinction background associated to the
      Miocene-Pliocene transition decimated the diversity within each major clade,
      resulting in the species-poor genera observed today. Our study supports a
      connection between high extinction rates and patterns of decoupled phenotypic
      evolution and lineage diversification, and the possibility of a radiation in the
      absence of ecological release.

PMID- 30273757
TI  - Genomic insights of Vibrio harveyi RT-6 strain, from infected "Whiteleg shrimp"
      (Litopenaeus vannamei) using Illumina platform.
AB  - The pathogenicity of "Vibriosis" in shrimps imposes prominent menace to the
      sustainable growth of mariculture economy. Often the disease outbreak is
      associated speciously with Vibrio harveyi and its closely related species. The
      present study investigated the complete genome of the strain V. harveyi RT-6 to
      explore the molecular mechanism of pathogenesis. The genome of V. harveyi
      possesses a single chromosome of 6,374,398 bp in size, G + C content (44.7%) and
      5730 protein coding genes. The reads of 1.3 Gb were retained from Illumina Hiseq
      2500 sequencing method, assembled into 5912 predicted genes, 114 tRNAs genes, and
      11 rRNAs genes. Unigenes were annotated by matching against Clusters of
      Orthologous Groups of proteins (COG)-5730, Gene ontology (GO)-1088, and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) databases-3401. Furthermore, 13
      insertion sequences-(IS), virulence factors and prophage regions were also
      identified. A total of 94 pathogenic genes and 36 virulence factor genes were
      mainly identified using Virulence Factors Database (VFDB). Out of the 36
      virulence factors, 23 genes responsible for encoding flagella-based motility
      protein were exclusively predicted to take part in pathogenic mechanism. The
      Whole Genome Sequencing (WGS) of the strain RT-6 (accession number: SRR5410471)
      highlighted the underlying genes and specifically accountable functional genes
      that were responsible for pathogenic infections in shrimps.

PMID- 30273758
TI  - Production of Sc medical radioisotopes with proton and deuteron beams.
AB  - Proton and deuteron beams (15.3 and 6.8 MeV, respectively) extracted from the
      PETtrace medical cyclotron at the Radiopharmaceuticals Production and Research
      Centre in the University of Warsaw, Heavy Ion Laboratory, 28 MeV protons from the
      C30 cyclotron at the National Centre for Nuclear Research, Swierk, near Warsaw
      and 33 MeV protons from the ARRONAX accelerator, Nantes were used to produce and
      investigate the medically interesting Sc radioisotopes. Both natural and
      isotopically enriched CaCO3 and TiO2 targets were used (42Ca, 43Ca, 44Ca, 48Ca,
      48Ti). The production efficiency and isotopic purity were determined and are
      reported here for the highest commercially available enrichments of the target
      material. The Thick Target Yield, Activities at the End of Bombardment (EOB) and
      the relative activities of produced impurities at EOB are reported for 43Sc,
      44gSc, 44mSc and 47Sc produced with particle energies below 33 MeV.

PMID- 30273760
TI  - Synthesis and thermoluminescence of erbium-activated lithium niobate.
AB  - Erbium-activated lithium niobate; 1, 2, and 4 mol% (LN-1, LN-2 and LN-4
      respectively) were synthesized by solid-state method and their thermoluminescent
      (TL) properties were analyzed. The glow curve of LN-4 showed a maximum at 177 
      degrees C and its linear dose-response interval ranged from 50 to 350 Gy. Its TL
      intensity was two orders of magnitude greater compared to those of pure lithium
      niobate (LN), LN-1 and LN-2. We conclude that LN-4 is an interesting material for
      TL dosimetry applications.

PMID- 30273759
TI  - 2.7 years of beta-decay-rate ratio measurements in a controlled environment.
AB  - We report nearly continuous beta-decay-rate measurements of Na-22, Cl-36, Co-60,
      Sr-90, and Cs-137 over a period of 2.7 years using four Geiger-Muller tubes. We
      carefully control the ambient pressure and temperature for the detectors,
      sources, and electronics in order to minimize environmentally-dependent
      systematic drifts in the measurement chains. We show that the amplitudes of an
      annual oscillation in the decay rates are consistent with zero to within 0.004%.

PMID- 30273761
TI  - Uncertainty evaluation in gamma spectrometric measurements: Uncertainty
      propagation versus Monte Carlo simulation.
AB  - Calculation and reporting of combined measurement uncertainties are important in
      decision making processes, and a more proper uncertainty estimation can reduce
      the risk and/or the cost associated with decisions for example after radiological
      incidents and in free release measurements of radioactive waste. However, sound
      decisions demand a sound uncertainty estimation. In this work we present the
      possible consequences when uncertainty propagation is applied to gamma-ray
      spectrometry measurements involving assumed probability density functions for an
      efficiency transfer having different metrological quality by comparison with
      Monte Carlo simulations.

PMID- 30273763
TI  - Internalization capabilities of gold-198 nanoparticles: Comparative evaluation of
      effects of chitosan agent on cellular uptake into MCF-7.
AB  - In this study, internalization of positively charged chitosan-coated
      nanoparticles (198AuNPs@chitosan) on MCF-7 cells was investigated by gamma-ray
      spectroscopy and then statistically compared to that of 198Au and negatively
      charged citrate-stabilized nanoparticles (198AuNPs). Sub-50 nm 198AuNPs@chitosan
      had a higher internalization compared to 198Au and 198AuNPs (p < 0.05). More
      cellular uptake of 198AuNP@chitosan means a higher dose of radioactivity to the
      tumor cells which, in turn, more effective treatment of the cancer.

PMID- 30273762
TI  - A method for determining density based on gamma ray and fast neutron detection
      using a Cs2LiYCl6 detector in neutron-gamma density logging.
AB  - With the increasing demand for radioisotope-free operations, pulsed neutron-gamma
      density (NGD) has become increasingly important for logging-while-drilling (LWD)
      development. However, current NGD tools, adopting the multiple-detector array
      design, are not conducive to the simplification of instrument design and
      measurement system. To break obstacles, based on the fast neutron-gamma coupled
      theory, a new density measurement method was proposed. Further, combined with the
      neutron-gamma simultaneous detection characteristics of the Cs2LiYCl6 (CLYC)
      detector, an NGD measurement system consisting of a D-T source and one CLYC
      detector was used. Results show that the new method is capable of determining
      formation density using a single CLYC detector, which can not only avoid complex
      instrument systems but also improve density sensitivity. Moreover, the
      applicability of the new density method was well verified by Monte Carlo
      simulation. Additionally, the method was successfully applied in a simulated
      well, and density results are in good agreement with the benchmarked formations.
      The research provides theoretical guidance for NGD instrument design.

PMID- 30273764
TI  - Radiation safety analysis for the A-BNCT facility in Korea.
AB  - A Proton Accelerator based Boron Neutron Capture Therapy (A-BNCT) facility is
      under development in Korea. Neutron beams for treatment are produced from a
      beryllium (Be) target and an 8 mA, 10 MeV proton beam. The purpose of the
      research is a radiation shielding analysis and an activation analysis for the
      facility design satisfying the radiation safety requirements as well as obtaining
      an operating license for the radiation facility according to a domestic nuclear
      commissioning procedure. The radiation shielding analysis was performed using the
      MCNPX computational particle transport code. The radiation source terms in the
      facility were evaluated and utilized in the shielding calculations. The minimum
      concrete thickness satisfying the designated dose rate of 5 MUSv/h for the
      worker's area and 0.25 MUSv/h for the public area were estimated and applied to
      the design. For an assessment of the radiation safety inside the facility, the
      dose rates were evaluated at several positions, such as behind the shielding
      door, around the primary barriers near the radiation sources, and in the
      penetrations of the ducts. The dose rate distribution was mapped for verification
      of the radiation safety for the entire facility. An activation analysis was
      carried out for the concrete walls, air, target assembly, beryllium target, and
      cooling water using FISPACT-2010 code. Concentrations of the activation products
      and dose rate induced by the radionuclides after shutdown were evaluated for the
      purpose of safe operation of the facility. The results were reviewed with the
      radiation safety regulations in Korea. As a result, it was proved that the final
      facility design satisfies the safety requirements.

PMID- 30273765
TI  - Foreign language reduces the longevity of the repetition-based truth effect.
AB  - Recent evidence suggests that judgment biases may diminish when a problem is
      presented in a foreign language. This foreign-language effect has primarily been
      examined with emotional materials such as risky-choice problems and moral
      dilemmas. In two experiments, we investigated the effect of foreign-language
      processing on an emotionally neutral judgment bias: the repetition-based truth
      effect, the phenomenon that statement repetition enhances the perceived truth of
      statements. In Experiment 1, we found no evidence for the truth effect to be
      moderated by the language in which the statements were processed (native
      language: Hungarian; foreign language: English). In Experiment 2, in turn, we not
      only manipulated language (native language: German; foreign language: English),
      but also the retention interval between statement repetitions. Replicating the
      findings of Experiment 1, language did not moderate the truth effect for
      statements that were repeated within the same experimental session. However,
      after a two-week interval, the truth effect was significantly smaller in the
      foreign-language condition than in the native-language condition. Overall, our
      findings suggest a faster decay of semantic memory for foreign-language as
      compared to native-language statements.

PMID- 30273766
TI  - Positive impact of pulmonary vein isolation on biventricular pacing in
      nonresponders to cardiac resynchronization therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is less effective in patients
      with atrial fibrillation (AF) because of impaired ventricular CRT capture.
      OBJECTIVE: We investigated the effects of catheter ablation in patients with AF
      and previous nonresponse to CRT. METHODS: Consecutive patients with AF and CRT
      nonresponse who underwent catheter ablation for AF were analyzed. CRT nonresponse
      was defined as one of the following: (1) reduced biventricular capture <95% due
      to rapidly conducted AF, (2) <1 point improvement in New York Heart Association
      (NYHA) class after CRT implantation, or (3) insufficient increase in left
      ventricular ejection fraction (LVEF; <=5%) after CRT implantation. RESULTS:
      Thirty-eight patients (8 women [21%]; mean age 68 +/- 10 years; LVEF 30% +/- 7%,
      biventricular capture 88.0% [25th, 75th percentile 75.3%, 98.5%]) underwent
      catheter ablation. One major and 1 minor complication occurred (1 lethal
      atrioesophageal fistula and 1 hemodynamically nonrelevant pericardial effusion).
      The Kaplan-Meier estimates for arrhythmia-free survival after single and multiple
      ablation procedures were 29% (95% confidence interval 16%-51%) and 67% (95%
      confidence interval 53%-86%) after 24 months. After a median follow-up of 817
      days (25th, 75th percentile 179, 1741 days), biventricular capture and LVEF were
      significantly higher (median [25th, 75th percentile] 99% [96%, 99%], difference
      8% [0.2%, 3.75%], P < .0001; mean 32.1% +/- 9.1%, difference 2.2% +/- 7.1%, P =
      .0225) and patients had a significantly lower functional NYHA class (28 of 37
      patients with improvement of at least 1 point; P < .0001). CONCLUSION: Catheter
      ablation of AF significantly improves CRT response in patients with heart failure
      and concomitant AF in terms of increased biventricular capture and LVEF and
      improved functional NYHA class.

PMID- 30273767
TI  - Temporal relationships between esophageal injury type and progression in patients
      undergoing atrial fibrillation catheter ablation.
AB  - BACKGROUND: Currently, little is known about the onset, natural progression, and
      management of esophageal injuries after atrial fibrillation (AF) ablation.
      OBJECTIVES: We sought to provide a systematic review on esophageal injury after
      AF ablation and identify temporal relationships between various types of
      esophageal lesions, their progression, and clinical outcomes. METHODS: A
      comprehensive search of PubMed and Web of Science was conducted until September
      21, 2017. All AF ablation patients who underwent upper gastrointestinal endoscopy
      within 1 week of the procedure were included. Patients with esophageal lesions
      were classified into 3 types by using our novel Kansas City classification: type
      1: erythema; type 2a: superficial ulcers; type 2b: deep ulcers; type 3a:
      perforation without communication with the atria; and type 3b: perforation with
      atrioesophageal fistula. RESULTS: Thirty studies met our inclusion criteria. Of
      the 4473 patients, 3921 underwent upper gastrointestinal evaluation. The overall
      incidence of esophageal injuries was 15% (570). There were 206 type 1 lesions
      (36%), 222 type 2a lesions (39%), and 142 type 2b lesions (25%). Six of 142 type
      2b lesions (4.2%) progressed further to type 3, of which, 5 were type 3a and 1
      was type 3b. All type 1 and type 2a and most type 2b lesions resolved with
      conservative management. One type 3a and 1 type 3b lesions were fatal.
      CONCLUSION: Based on our classification, all type 1 and most type 2 lesions
      resolved with conservative management. A small percentage (4.2% [6 of 142]) of
      type 2b lesions progressed to perforation and/or fistula formation, and these
      patients need to be followed closely.

PMID- 30273768
TI  - Model-based learning and individual differences in depression: The moderating
      role of stress.
AB  - Inflexible decision-making has been proposed as a transdiagnostic risk factor for
      mood disorders. Evidence suggests that inflexible decision-making may emerge only
      when individuals are experiencing increased negative affect or stress. 151
      participants completed symptom measures of depression and anxiety, followed by a
      two-stage decision-making task that distinguishes between habitual and goal
      directed choice. An experimental manipulation to induce stress was introduced
      halfway through the task. Individuals with higher depression levels became less
      model-based after the manipulation than those with lower depression levels. There
      was no relationship between trait anxiety and the impact of the manipulation on
      decision-making. Controlling for main effects of anxiety did not attenuate the
      association between depression and impact of stress. Anhedonia was associated
      with the impact of the manipulation on model-based decision-making. These results
      suggest that risk for depression is associated with reflexive decision-making,
      but these effects may only emerge under conditions of stress.

PMID- 30273769
TI  - Utilization of centrate for the outdoor production of marine microalgae at the
      pilot-scale in raceway photobioreactors.
AB  - In this study, the outdoor production of marine microalgae in raceway
      photobioreactors was investigated, modifying the centrate percentage in the
      culture medium (20, 30, 40 and 50%) and using two different dilution rates (0.2
      day-1 and 0.3 day-1). The data obtained showed that microalgae are capable of
      producing biomass in addition to recovering the nutrients contained in the
      centrate. The best results for biomass productivity and light efficiency were
      obtained when the centrate was set at 20% with a dilution rate of 0.3 day-1. The
      biomass productivity was 32.42 g m-2.day-1 while the photosynthetic efficiency
      was 0.74 gbiomass.E-1 (3.66%). Regarding the nutrients, nitrogen (the majority
      being in the form of ammonium [NH4+]) and phosphorus were only fixed into biomass
      when optimal conditions were set; if this was not the case, they were lost to
      stripping or precipitation. The maximal nutrient removal capacities under the
      optimal conditions were 28.72 mgN.l-1.day-1 and 3.99 mgP.l-1.day-1. Population
      changes were determined by the dilution rate set whilst the centrate percentage
      had little effect. Four strains were present in the culture, Nannochloropsis g.
      being the main one. Biochemical changes did not vary greatly between the
      conditions set for the culture, with a composition rich in proteins and
      carbohydrates being observed. One can conclude that to produce marine microalgal
      biomass for a range of potential commodities such as feed, biofertilizers and
      biofuels, it is possible to use centrate from anaerobic digestion as the sole
      nutrient source, as a way of reducing costs.

PMID- 30273770
TI  - Use of facebook to engage water customers: A comprehensive study of current U.K.
      and Australian practices and trends.
AB  - Given regulatory developments, it is imperative that water businesses implement
      effective customer engagement strategies. Among other options, Facebook offers
      enormous potential given the ability to connect with customers, involve customers
      in the co-creation of content, obtain real-time feedback on customer preferences
      and promote water conversation behaviours. This paper examines how effectively 20
      large Australian and U.K. water businesses are using Facebook to engage
      customers. It also identifies how these firms can improve Facebook engagement by
      optimising posts type, timing, content, frequency and other factors. The total
      sample included more than 300,000 responses to nearly 17,000 posts between 2010
      and 2017. Rapid growth in the utilisation of Facebook by water businesses was
      observed given the number of posts and customers engaging with this content. The
      results of the analysis of popular posts identified innovative ways some water
      businesses are using Facebook posts to promote the health benefits of tap water
      consumption, water conservation behaviours and responsible wastewater practices.
      Despite the trends, most firms still make less than one post per day and of those
      customers who have engaged, most have done with a single response. Further
      analysis revealed that few posts, and only a relatively small number of customer
      comments, pertained to water pricing matters. To promote engagement, water
      businesses must improve post regularity, the degree to which they moderate
      Facebook discussion, the utilisation of videos and photos, and further consider
      the underlying content of posts.

PMID- 30273771
TI  - Two-way switch: Maximizing productivity of tilted panel in membrane bioreactor.
AB  - Membrane fouling is a major challenge in membrane bioreactors (MBRs) and its
      effective handling is the key to improve their competitiveness. Tilting panel
      system offers significant improvements for fouling control but is strictly
      limited to one-sided panel. In this study, we assess a two-way switch tilting
      panel system that enables two-sided membranes and project its implications on
      performance and energy footprint. Results show that tilting a panel improves
      permeance by up to 20% to reach a plateau flux thanks to better contacts between
      air bubbles and the membrane surface to scour-off the foulant. A plateau
      permeance could be achieved at aeration rate of as low as 0.90 l min-1, a
      condition untenable by vertical panel even at twice of the aeration rate.
      Switching at short periods (<5min) can maintain the hydraulic performance as in
      no-switch (static system), enables application of a two-sided switching panel. A
      comparison of vertical panel under 1.80 l min-1 aeration rate with a switching
      panel at a half of the rate, switched at 1 min period shows ~10% higher permeance
      of the later. Since periodic switching consumes a very low energy (0.55% of the
      total of 0.276 kWh m-3), with reduction of aeration by 50%, the switching tilted
      panel offers 41% more energy efficient than a referenced full-scale MBR (0.390
      kWh m-3). Overall results are very compelling and highly attractive for
      significant improvements of MBR technologies.

PMID- 30273772
TI  - Introducing nano-particle-type properties of Tin (n=2-6) clusters.
AB  - In the present research titanium clusters, Tin (n = 2-6), are studied to
      highlight their tendency to present nano-particle-type properties as their size
      grows. Electronic and geometrical structures of clusters and cluster-ligands
      complexes are obtained at the PBE/QZVP level of theory after density functional
      theory (DFT) calibration. The correlation between chemical reactivity (hardness)
      and conductivity with nano-particle-type properties are introduced. Interaction
      energies of these clusters with N2 and C2H4 ligands are calculated to provide
      essential information regarding the ascending trend of reactivity as the size of
      cluster increases. For reactivity, the correlation between the hardness values of
      titanium clusters and interaction energies are found to be R2 = 0.972 for
      dissociative adsorption. In addition, the correlation between non-Lewis of pure
      titanium clusters and size of clusters is R2 = 0.973. For conductivity, the
      obtained correlation between HOMO-LUMO gap values and the cluster size is R2 =
      0.881.

PMID- 30273773
TI  - Modeling protic dicationic ionic liquids based on quaternary ammonium,
      imidazolium or pyrrolidinium cations and bis(trifluoromethanesulfonyl)imide
      anion: Structure and spectral characteristics.
AB  - Protic dicationic ionic liquids (PDILs) have attracted growing attention owing to
      their applications in domains of electrochemistry, proton conducting materials
      and other diverse areas. In the present work protic dicationic ionic liquids
      (PDILs) comprising of quaternary ammonium-, imidazolium- or pyrrolidinium
      dications and bis(trifluoromethanesulfonyl)imide (Tf2N?) anion have been modelled
      as the dication-(Tf2N)2 complexes. Electronic structure, vibrational and 1H NMR
      spectra of these complexes have been derived employing the M06-2x density
      functional theory. Theoretical calculations have shown that the strength of
      cation-anion binding follows the order: methylpyrrolidinum > quaternary ammonium
      > butylpyrrolidinium > imidazolium, which can be attributed to number and
      strength of N-H---O and C-H---O interactions. The dication-(Tf2N)2 complexes
      emerge with signature in frequency up-shift of the characteristic N-H stretching
      in their infrared spectra. Underlying molecular interactions are unveiled through
      natural bond orbital analyses, Quantum theory of atoms in molecules (QTAIM) and
      noncovalent interaction reduced density gradient method. The calculations have
      shown that cation-anion binding energies increase linearly with kinetic energy
      density component G(r) in QTAIM analysis and proton affinities in the PDILs. A
      correlation between change in free energies accompanying the dication-(Tf2N)2
      complexes and proton affinities has also been established.

PMID- 30273774
TI  - Growth hormone and Insulin-like growth factor-I (IGF-I) modulate the expression
      of L-type amino acid transporters in the muscles of spontaneous dwarf rats and L6
      and C2C12 myocytes.
AB  - OBJECTIVE: Branched-chain amino acids (BCAAs) have been reported to inhibit
      several types of muscle atrophy via the activation of the mechanistic target of
      rapamycin complex 1 (mTORC1). However, we previously found that BCAA did not
      activate mTORC1 in growth hormone (GH)-deficient spontaneous dwarf rats (SDRs),
      and that GH restored the stimulatory effect of BCAAs toward the mTORC1. The
      objective of this study was to determine whether GH or Insulin-like growth factor
      I (IGF-I) stimulated the expression of L-type amino acid transporters (LATs) that
      delivered BCAAs, and whether LATs were involved in the mTORC1 activation. DESIGN:
      After the continuous administration of GH, cross-sectional areas (CSAs) of muscle
      fibers and LAT mRNA levels in the skeletal muscles of SDRs were compared to those
      from the SDRs that received normal saline. The effect of GH and IGF-I on LAT mRNA
      levels were determined in L6 and C2C12 myocytes. The effects of 2
      aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH), a blocker for LATs, and LAT1
      siRNA on mTORC1 activation and cell functions were examined in C2C12 cells.
      RESULTS: GH increased LAT1 and LAT4 mRNA levels in accordance with the increase
      in CSAs of muscle fibers in SDRs. IGF-I, and not GH, increased LAT1 mRNA levels
      in cultured L6 myocytes. IGF-I also increased LAT1 mRNA level in another myocyte
      line, C2C12. Furthermore, IGF-I reduced LAT3 and LAT4 mRNA levels in both cell
      lines. GH reduced LAT3 and LAT4 mRNA levels in L6 cells. BCH decreased basal
      C2C12 cell proliferation and reduced IGF-I-induced phosphorylation of 4E-BP1 and
      S6K, both of which are mTORC1 targets, but LAT1 siRNA did not affect the
      phosphorylation. This suggests that BCH may exert its effect via other pathway
      than LAT1. CONCLUSIONS: IGF-I increased LAT1 mRNA level in myocytes. However, the
      role of LAT1 in IGF-I-induced mTORC1 activation and cell functions remains
      unclear.

PMID- 30273775
TI  - 'Recurrent losers unite': Online forums, evidence-based activism, and pregnancy
      loss.
AB  - Women with recurrent pregnancy loss face unique challenges associated with the
      social invisibility of their condition, patchy medical knowledge about it, and
      often intransigent positions of doctors. We approach online forums as sites of
      knowledge production and examine discussions among women with recurrent
      miscarriages. We observe that some forum participants gather, summarize, and
      share experience-based and research-based information in order to challenge
      certain medical conceptions. We describe these efforts as an example of
      individual patients' evidence-based activism enabled by new media platforms and
      other technoscientific tools available to the public.

PMID- 30273776
TI  - Watch for motorcycles! The effects of texting and handheld bans on motorcyclist
      fatalities.
AB  - Motorcyclists account for a much higher proportion of traffic fatalities relative
      to the share of motorcycles among all motor vehicles and vehicle miles driven in
      the U.S. In this paper, we posit that motorcyclists may be particularly
      vulnerable to the risks of distracted driving by others. Specifically, we examine
      whether state-specific texting/handheld bans significantly influence motorcyclist
      fatalities in the U.S. We use state-specific traffic fatality data in the U.S.
      (2005-2015, N = 550) from the Fatality Analysis Reporting System (FARS) merged
      with state-specific characteristics, texting/handheld device laws, and other
      traffic policies. Although research is mixed on the effectiveness of
      texting/handheld bans for overall traffic fatalities, our findings indicate that
      motorcyclists are at elevated risk of being a victim of distracted driving and
      thus could greatly benefit from these policies. This result is driven mainly by
      multiple-vehicle crashes (e.g., car hitting motorcycle) as opposed to single
      vehicle crashes. Policy makers should consider strengthening texting/handheld
      bans along with their enforcement to improve safety and save lives, especially
      among motorcyclists. .

PMID- 30273777
TI  - Parental recognition of preadolescent mental health problems: Does stigma matter?
AB  - RATIONALE: Parents are one of several key gatekeepers to mental health (MH)
      services for adolescents with MH problems. Parental MH stigma is a significant
      barrier to treatment, yet little is known about how stigma may bias parental
      recognition of mental illness in youth. OBJECTIVE: This study examines how stigma
      influences a critical and early stage of the help-seeking process-the recognition
      of MH problems in preadolescents by their parents. METHOD: Parents from a school
      based anti-stigma intervention study were analyzed. Logistic regressions examined
      the association of stigma with parental recognition of MH problems in their
      preadolescent child (10-12 years old) and that of two preadolescent vignette
      characters described as having bipolar disorder and social anxiety disorder.
      RESULTS: The more parents desired their preadolescent child to avoid interaction
      with individuals with a mental illness-that is, to be more socially distant-the
      less likely these parents believed their child had a MH problem, controlling for
      parent-reported MH symptoms and other covariates. This pattern was prominent
      among parents who reported high symptoms in their child. Social distance had no
      bearing on whether parents recognized the vignette characters as having a
      problem. Avoidance of individuals with a mental illness and knowledge/positive MH
      attitudes were not associated with problem recognition. CONCLUSION: Stigmatizing
      attitudes of parents may be detrimental when trying to understand the
      psychopathology of their own preadolescent children but not preadolescents
      outside their family. Stigma may present itself as a barrier to problem
      recognition because it may impose a significant personal cost on the family,
      thereby affecting the help-seeking process earlier than considered by previous
      work.

PMID- 30273778
TI  - A Nanopore Sequencing-Based Assay for Rapid Detection of Gene Fusions.
AB  - Structural chromosomal rearrangements leading to gene fusions are strong driver
      mutations in a variety of tumors. Identification of specific gene fusions can be
      essential for distinguishing benign from malignant conditions and for recognizing
      specific subtypes of neoplasms that can have different management and prognosis.
      Rapid identification of gene fusions is particularly critical for patients with
      acute leukemia who cannot wait more than a few days before initiating treatment
      and for whom treatment can be dramatically different depending on the leukemia
      subtype. We have developed an assay for rapid detection of oncogenic gene fusions
      (within 24 hours) that takes advantage of the long reads and real-time data
      generation of the Oxford Nanopore MinION sequencing system. By using a
      modification of the anchored multiplex PCR method for library construction, we
      confidently identified BCR-ABL1 fusion transcripts, with >100 reads within 15
      minutes of sequencing. By using formalin-fixed, paraffin-embedded specimens
      routinely tested in our clinical molecular laboratory, fusions were successfully
      identified within 5 hours from acquisition of Illumina-ready libraries and 30
      minutes of sequencing initiation, including cases diluted to a tumor fraction of
      5%. In conclusion, we have developed a nanopore-based sequencing assay that can
      decrease turnaround time for detection of fusion oncogenes and may be a valid
      approach for laboratories with low specimen volume and for cases in need of rapid
      results.

PMID- 30273779
TI  - In Silico Mutator: In Silico MutatorSoftware for Bioinformatics Pipeline
      Validation of Clinical Next-Generation Sequencing Assays.
AB  - Lack of reliable reference samples containing different mutations of interest
      across large sets of disease-relevant loci limits the extensive validation
      clinical next-generation sequencing (NGS) assays and their associated
      bioinformatics pipelines. Herein, we have generated a publicly available, highly
      flexible tool, in silico Mutator (insiM), to introduce point mutations,
      insertions, deletions, and duplications of any size into real data sets of
      amplicon-based or hybrid-capture NGS assays. insiM accepts an alignment file
      along with target territory and produces paired-end FASTQ files containing
      specified mutations via modification of original sequencing reads. Mutant signal
      is, thus, generated within the context of existing real-world data to most
      closely mimic assay performance. Resulting files may then be passed through the
      assay's bioinformatics pipeline to assist with assay/bioinformatics validation
      and to identify performance gaps in detection. To establish the basic
      functionality of the software, a series of simulation experiments with varying
      mutation types, sizes, and allele frequencies were performed across the entire
      clinical territory of hybrid-capture and amplicon-based clinical assays developed
      at The University of Chicago. This work demonstrates the utility of insiM as a
      supplementary tool during the validation of an NGS assay's bioinformatics
      pipeline.

PMID- 30273780
TI  - Accurate and Sensitive Analysis of Minimal Residual Disease in Acute Myeloid
      Leukemia Using Deep Sequencing of Single Nucleotide Variations.
AB  - Minimal residual disease (MRD) in acute myeloid leukemia (AML) is of major
      prognostic importance. The genetic landscape of AML is characterized by numerous
      somatic mutations, which constitute potential MRD markers. Leukemia-specific
      mutations can be identified with exome sequencing at diagnosis and assessed
      during follow-up at low frequencies by using targeted deep sequencing. Our aim
      was to further validate this patient-tailored assay for substitution mutations.
      By applying a statistical model, which corrects for position-specific errors, a
      limit of detection for single nucleotide variations of variant allele frequency
      (VAF) of 0.02% was achieved. The assay was linear in MRD range (0.03% to 1%) with
      good precision [CV, 4.1% (2.2% to 5.7%) at VAF 1% and 13.3% (8.8% to 19.4%) at
      VAF 0.1%], and low relative bias [7.9% (2.5% to 15.3%) at VAF 1%]. When applied
      to six childhood AML cases and compared with multiparameter flow cytometry for
      MRD analysis, deep sequencing showed concordance and superior sensitivity.
      Further high concordance was found with expression of fusion transcripts RUNX1
      RUNX1T1 and KMT2A-MLLT10. The deep sequencing assay also detected mutations in
      blood when VAF in bone marrow exceeded 0.1% (n = 19). In conclusion, deep
      sequencing enables reliable detection of low levels of residual leukemic cells.
      Introduction of this method in patient care will allow for highly sensitive MRD
      surveillance in virtually every patient with AML.

PMID- 30273781
TI  - Plastic surgery or primary care? Altruistic preferences and expected specialty
      choice of U.S. medical students.
AB  - Understanding physicians' decisions when faced with conflicts between their own
      financial self-interest and patients' economic or health interests is of key
      importance in health economics and policy. This issue is especially salient in
      certain medical specialties where less altruistic behavior of physicians can
      yield significant financial gains. This study examines experimentally measured
      altruistic preferences of medical students from schools around the U.S., and
      whether these preferences predict those students' expected medical specialty
      choice. The experimental design consists of a set of computer-based revealed
      preference decision problems, which ask the experimental subjects to allocate
      real money between themselves and an anonymous person. These data are used to
      derive an innovative measure of altruism for each participant. I then examine the
      association between altruism and expected specialty choice, after controlling for
      an extensive set of covariates collected from an accompanying survey
      questionnaire. Medical students with a lower degree of altruism are significantly
      more likely to choose high-income specialties, conditioning on an extensive set
      of covariates. This altruism measure is more predictive of income of specialty
      choice than a wide range of other characteristics, including parental income,
      student loan amount and Medical College Admission Test (MCAT) score. On the other
      hand, the altruism measure does not predict choosing primary care specialties. I
      also find that altruism predicts students' self-reported likelihood of practicing
      medicine in an underserved area.

PMID- 30273782
TI  - Environmental pollution and toxic substances: Cellular apoptosis as a key
      parameter in a sensible model like fish.
AB  - The industrial wastes, sewage effluents, agricultural run-off and decomposition
      of biological waste may cause high environmental concentration of chemicals that
      can interfere with the cell cycle activating the programmed process of cells
      death (apoptosis). In order to provide a detailed understanding of environmental
      pollutants-induced apoptosis, here we reviewed the current knowledge on the
      interactions of environmental chemicals and programmed cell death. Metals
      (aluminum, arsenic, cadmium, chromium, cobalt, zinc, copper, mercury and silver)
      as well as other chemicals including bleached kraft pulp mill effluent (BKME),
      persistent organic pollutants (POPs), and pesticides (organo-phosphated, organo
      chlorinated, carbamates, phyretroids and biopesticides) were evaluated in
      relation to apoptotic pathways, heat shock proteins and metallothioneins.
      Although research performed over the past decades has improved our understanding
      of processes involved in apoptosis in fish, yet there is lack of knowledge on
      associations between environmental pollutants and apoptosis. Thus, this review
      could be useful tool to study the cytotoxic/apoptotic effects of different
      pollutants in fish species.

PMID- 30273783
TI  - A lipidomic approach to understand copper resilience in oyster Crassostrea
      hongkongensis.
AB  - Copper (Cu) can cause oxidative stress and inflammatory responses, and there is
      arising evidence between Cu toxicity and lipid disturbance. In this study, we
      examined the relationships between Cu exposure and lipid metabolism in an
      estuarine oyster (Crassostrea hongkongensis) and aimed to understand the effects
      and resilience strategies of Cu on oyster metabolism. We exposed the oysters to
      waterborne Cu (10 and 50 MUg/L) and measured the physiological changes (condition
      index and clearance rate), lipid accumulation and lipid peroxidation in the
      oysters. We found more altered lipid responses in oysters exposed to a lower Cu
      concentration (10 MUg/L), and speculated that oysters exposed to 50 MUg/L may
      upregulate the defenses. We further evaluated the changes in lipidome profiling
      of the Cu-exposed oysters in aspects of membrane dynamics, lipid signaling and
      energy metabolism. We documented the phospholipid remodeling as well as quick
      modulation in inflammatory responses and extensive vesicle formation for
      subcellular compartmentalization and autophagosome formation, as well as the
      possible impacts on mitochondrial bioenergetics in the Cu-exposed oysters. The
      lipidomics approach provided a comprehensive lipid profile of possible alteration
      by Cu exposure. In combination with other omics approaches, it may be possible to
      elucidate the pathways and mechanisms in stress acclimation and resilience
      associated between Cu contamination and lipid metabolism.

PMID- 30273784
TI  - Serum cytokine profiles in patients with chronic obstructive pulmonary disease
      associated pulmonary hypertension identified using protein array.
AB  - Pulmonary hypertension (PH) is a common complication of chronic obstructive
      pulmonary disease (COPD) and is a significant risk factor for hospitalization and
      shortened life expectancy. Therefore, developing new serum biomarkers for early
      diagnosis and prognosis of COPD associated PH is crucial. In the present study, a
      solid-phase antibody array simultaneously detecting multiple proteins was used to
      search specific COPD associated PH biomarkers, with COPD patients and healthy
      subjects as control groups. As a result, compared to the COPD and healthy groups,
      the levels of MCP-4, SDF-1 alpha, CCL28, Adipsin, IL-28A, CD40 and AgRP were
      uniquely altered in COPD patient serum with pulmonary hypertension. Among these
      proteins, CCL28, MCP-4, CD40, AgRP and IL-28A were identified to be
      differentially expressed in COPD patients with hypertension, indicating that
      these cytokines may serve as novel biomarkers for the diagnosis and prognosis of
      COPD associated pulmonary hypertension.

PMID- 30273785
TI  - Anacardic acid suppresses fibroblast-like synoviocyte proliferation and invasion
      and ameliorates collagen-induced arthritis in a mouse model.
AB  - Anacardic acid, which is abundant in nutshell of Anacardium occidentale, has
      multiple pharmacological activities. In this study, we examined the therapeutic
      potential of anacardic acid in treating rheumatoid arthritis (RA). We explored
      the effects of anacardic acid on collagen-induced arthritis (CIA) in mice and on
      the proliferation and invasion of RA fibroblast-like synoviocytes (RA-FLSs). The
      underlying molecular mechanism was investigated. Anacardic acid treatment
      markedly suppressed paw swelling, joint destruction, and arthritis scores in CIA
      mice. The serum levels of tumor necrosis factor alpha (TNF- alpha) and
      interleutkin-1beta (IL- 1beta) were significantly lowered by anacardic acid. In
      vitro assays demonstrated that anacardic acid impaired the proliferation and
      invasion abilities of RA-FLSs in the presence of TNF- alpha or IL- 1beta. Western
      blot analysis revealed the reduction of Akt protein expression and
      phoshporylation in RA-FLSs by anacardic acid. However, the mRNA level of Akt
      remained unchanged. Anacardic acid treatment significantly increased the
      expression of miR-633 in RA-FLSs. Akt was identified as a novel target of miR
      633. Overexpression of miR-633 significantly inhibited the proliferation and
      invasion of RA-FLSs, which was rescued by enforced expression of Akt. Depletion
      of miR-633 prevented anacardic acid-mediated suppression of proliferation and
      invasion of RA-FLSs, which was accompanied by increased expression of Akt
      protein. In conclusion, anacardic acid may serve as a promising agent in the
      treatment of RA.

PMID- 30273786
TI  - Reduction of bacterial integrity associated with dam construction: A quantitative
      assessment using an index of biotic integrity improved by stability analysis.
AB  - Rivers are extensively regulated by damming, yet the effects of such interruption
      on bacterial communities have not been assessed quantitatively. To fill this gap,
      we proposed a bacteria-based index of biotic integrity (Ba-IBI) by using
      bacterial community dataset collected from the Three Gorges Reservoir and its
      upper reaches. Stability analysis based on bacterial resistance (RS) and
      resilience (RL) to external disturbance was conducted to improve the performance
      of the index. Four core metrics, i.e. the ratio of Bacilli, Bacteroidetes and
      Clostridia to Alphaproteobacteria (BBC/A), Oxalobacteraceae, Methanotrophs and
      Thermophiles were selected after range, responsive and redundancy tests. The
      improved Ba-IBI, ranging from 1.04 to 4.10, was better at distinguishing sites
      with or without direct dam effects compared with the unimproved one. The index
      values maintained high in the riverine sites while reducing in the reservoir,
      demonstrating the negative influence of dam construction on bacterial integrity.
      Based on the assessment results, 23.1%, 46.2% and 30.8% sampling sites were
      large, moderately and little affected by damming, respectively. A Random Forest
      (RF) regression model was trained and tested, offering a valid prediction of the
      input Ba-IBI and environmental parameters. Sensitivity analysis revealed the
      significant contributions of flow velocity towards the predicting process
      performance, indicating the importance of hydrodynamic conditions on determining
      the spatial variability of bacterial communities. This study provides not only a
      first quantitative insight for assessing bacterial response to damming, but also
      a guideline for applying the improved index in the dam regulation and ecological
      protection.

PMID- 30273787
TI  - Considerations for upscaling individual effects of wind energy development
      towards population-level impacts on wildlife.
AB  - The expansion of wind energy poses challenges to policy- and decision-makers to
      address conflicts with wildlife. Conflicts are associated with impacts of
      existing and planned projects on wildlife, and associated difficulties of
      prediction where impacts are subject to considerable uncertainty. Many post
      construction studies have demonstrated adverse effects on individuals of various
      bird and bat species. These effects may come in the form of collision-induced
      mortality or behavioral or physiological changes reducing the fitness of
      individuals exposed to wind energy facilities. Upscaling these individual effects
      to population impacts provides information on the true value of interest from a
      conservation point of view. This paper identifies methodological issues
      associated when moving from individual effects to population impacts in the
      context of wind energy. Distinct methodological approaches to predict population
      impacts are described using published case studies. The various choices of study
      design and metrics available to detect significant changes at the population
      level are further assessed based on these. Ways to derive impact thresholds
      relevant for decision-making are discussed in detail. Robust monitoring schemes
      and sophisticated modelling techniques may inevitably be unable to describe the
      whole complexity of wind and wildlife interactions and the natural variability of
      animal populations. Still, they will provide an improved understanding of the
      response of wildlife to wind energy and better-informed policies to support risk
      based decision-making. Policies that support the use of adaptive management will
      promote assessments at the population level. Providing information to adequately
      balance the development of wind energy with the persistence of wildlife
      populations.

PMID- 30273788
TI  - How practitioners integrate decision triggers with existing metrics in
      conservation monitoring.
AB  - Decision triggers are defined thresholds in the status of monitored variables
      that indicate when to undertake management, and avoid undesirable ecosystem
      change. Decision triggers are frequently recommended to conservation
      practitioners as a tool to facilitate evidence-based management practices, but
      there has been limited attention paid to how practitioners are integrating
      decision triggers into existing monitoring programs. We sought to understand
      whether conservation practitioners' use of decision triggers was influenced by
      the type of variables in their monitoring programs. We investigated this question
      using a practitioner-focused workshop involving a structured discussion and
      review of eight monitoring programs. Among our case studies, direct measures of
      biodiversity (e.g. native species) were more commonly monitored, but less likely
      to be linked to decision triggers (10% with triggers) than measures being used as
      surrogates (54% with triggers) for program objectives. This was because decision
      triggers were associated with management of threatening processes, which were
      often monitored as a surrogate for a biodiversity asset of interest. By contrast,
      direct measures of biodiversity were more commonly associated with informal
      decision processes that led to activities such as management reviews or external
      consultation. Workshop participants were in favor of including more formalized
      decision triggers in their programs, but were limited by incomplete ecological
      knowledge, lack of appropriately skilled staff, funding constraints, and/or
      uncertainty regarding intervention effectiveness. We recommend that practitioners
      consider including decision triggers for discussion activities (such as external
      consultation) in their programs as more than just early warning points for future
      interventions, particularly for direct measures. Decision triggers for
      discussions should be recognized as a critical feature of monitoring programs
      where information and operational limitations inhibit the use of decision
      triggers for interventions.

PMID- 30273789
TI  - Predictors of long-term outcome of CBT for youth with anxiety disorders treated
      in community clinics.
AB  - Cognitive behavioral therapy (CBT) has proven long-term effects in youth with
      anxiety disorders. However, only a few studies have examined predictors of long
      term outcomes of CBT treatment. The present study investigated possible
      predictors of long-term treatment outcomes in youth with mixed anxiety disorders
      treated in community mental health clinics. A total of 139 youth (mean age at
      assessment 15.5 years, range 11-21 years) with a principal diagnosis of
      separation anxiety disorder, social anxiety disorder, and/or generalized anxiety
      disorder were evaluated a mean of 3.9 years post-treatment (range 2.2-5.9 years).
      Outcomes were loss of all inclusion anxiety diagnoses, loss of the principal
      inclusion anxiety diagnosis, and changes in youth- and parent-rated youth anxiety
      symptoms. Predictors encompassed youth, parent and demographic factors, and post
      treatment recovery. The most consistent finding was that low family social class
      predicted poorer outcomes. Higher treatment motivation was associated with better
      outcome whereas a diagnosis of social anxiety was associated with poorer outcome.
      Identified predictors extend on previous findings from efficacy trials, and the
      results indicate a need for more specific treatment protocols.

PMID- 30273790
TI  - Use of cooking oils in a 2:1 ratio classical ketogenic diet for intractable
      pediatric epilepsy: Long-term effectiveness and tolerability.
AB  - BACKGROUND: In many parts of eastern Asia, rice is a dietary staple and therefore
      the ketogenic diet (KD) can be difficult to administer. The aim of this study was
      to assess the long-term effectiveness and tolerability of the classical KD using
      a 2:1 ratio of fat to protein plus net carbohydrates, which is lower than the
      ratios of 3:1 or 4:1 typically used in classical KD for intractable pediatric
      epilepsy. MATERIALS: In this prospective study, cooking oils rich in
      polyunsaturated fatty acid or omega 3 fatty acids, such as olive oil, camellia
      oil, linseed oil, grape seed oil, and/or perilla oil were used to formulate a
      classical KD with a 2:1 ratio for infants and children diagnosed with medically
      intractable epilepsy from April 2002 to April 2018. Subjects received the diet
      for at least 3 months. The efficacy of the diet was analyzed at 3, 6, 12, and 24
      months, and at > 3 years. Tolerability during the period of diet administration
      was analyzed by medical records and parental reports. RESULTS: Sixty-three
      subjects, 29 males and 34 females, were enrolled from April 2002 to April 2018.
      The median age at diet initiation was 2 years 11 months. The median duration of
      adherence to the diet was 1 year 2 months. The seizure-free rate was 14%, 16%,
      17%, 14%, and 14% at 3, 6, 12, and 24 months', and at > 3 years' follow-up,
      respectively. A greater than 50% seizure reduction was achieved in 52%, 43%, 40%,
      33%, and 30% of subjects at each time point. The dietary compliance rate was
      100%, 70%, 60%, 35%, and 27% at each follow-up time point. The reasons for
      discontinuation of the KD were the lack of further improvement in seizure
      frequency, seizure freedom achieved, food refusal, hyperlipidemia, and poor
      parental compliance in 38%, 11%, 5%, 2%, and 2% of subjects, respectively.
      Gastrointestinal discomfort was the most common adverse effect. CONCLUSION: The
      classical KD with a 2:1 ratio showed clinical effectiveness and tolerability in
      intractable pediatric epilepsy after long-term follow-up.

PMID- 30273791
TI  - Clinical and imaging features distinguishing Susac syndrome from primary angiitis
      of the central nervous system.
AB  - INTRODUCTION: To assess clinical and/or imaging features useful to distinguish
      between Susac syndrome (SuS) and primary angiitis of central nervous system
      (PACNS). METHODS: Multicenter retrospective analysis of two cohorts of Argentine
      patients diagnosed with SuS and PACNS. RESULTS: 13 patients diagnosed with SuS (6
      women and 7 men, mean age 35 +/- 10 years) and 15 with PACNS (10 women and 5 men,
      mean age 44 +/- 18 years) were analyzed. Cognitive impairment (11 out of 13
      patients vs. 5 out of 15, p = .006), ataxia (7 out of 13 vs. 2 out of 15, p =
      .042) and auditory disturbances (7 out of 13 vs. 0 out of 15, p = .003) were more
      frequent in SuS patients; whereas seizures were more frequent in PACNS patients
      (8 out of 15 vs. 1 out of 13, p = .035). On MRI, corpus callosum (CC) involvement
      was observed more often in SuS, with abnormalities in CC genu, in 13 out of 13
      SuS patients vs. only 2 out of 15 PACNS patients (p < .001); in CC body these
      were present in 13 out of 13 SuS patients vs. 1 out of 15 PACNS patients, (p <
      .001); and in CC splenium in 12 out of 13 Sus patients vs. 1 of 15 PACNS, p <
      .001). Cortical lesions were more frequent in PACNS patients (10 out of 15 vs. 3
      out of 13 SuS patients, p = .02), as were hemorrhages (5 out of 15 vs. 0 out of
      13 SuS, p = .04) and multiple basal ganglia infarcts (7 out of 15 vs. 1 out of 13
      Sus, p = .037). CONCLUSION: Specific clinical and/or MRI findings may help
      distinguish SuS from PACNS with potential therapeutic implications.

PMID- 30273792
TI  - Alexithymia and reactive aggression: The role of the amygdala.
AB  - Past research suggests an association between reactive aggression and
      alexithymia, but neural mechanisms underlying this association remain unknown.
      Furthermore, the relationship between proactive aggression and alexithymia
      remains untested. This study aimed to: (1) test whether alexithymia is more
      related to reactive than proactive aggression; and (2) determine whether
      amygdala, insula, and/or anterior cingulate cortical (ACC) volume could be
      neurobiological mechanisms for this association. One hundred and fifty-six
      community males completed the Reactive-Proactive Aggression Questionnaire and the
      Toronto Alexithymia Scale. Amygdala, insula, and ACC volumes were assessed using
      MRI. Alexithymia was positively associated with reactive but not proactive
      aggression. Alexithymia was positively and bilaterally associated with amygdala
      and anterior cingulate volumes. Reactive aggression was positively associated
      with right amygdala volume. Controlling for right amygdala volume rendered the
      alexithymia-reactive aggression relationship non-significant. Results suggest
      that increased right amygdala volume is a common neurobiological denominator for
      both alexithymia and reactive aggression. Findings suggest that greater right
      hemisphere activation may reflect a vulnerability to negative affect, which in
      turn predisposes to experiencing negative emotions leading to increased
      aggression. Findings are among the first to explicate the nature of the
      alexithymia-aggression relationship, with potential clinical implications.

PMID- 30273793
TI  - White matter microstructural correlates of relapse in alcohol dependence.
AB  - Identification of neural correlates of relapse to alcohol after treatment is
      clinically important as it may inform better substance abuse treatment. Few
      studies have specifically analyzed the white matter microstructure in treatment
      seekers as it might relate to relapse risk versus long-term abstinence. Using 4
      Tesla diffusion tensor imaging, we compared two groups of one-month-abstinent
      treatment-seekers, who were classified based on their drinking status between six
      and nine months after treatment initiation. We hypothesized that subsequent
      relapsers had greater white matter microstructural deficits in specific brain
      regions than long-term abstainers. At one month of abstinence, 37 future
      relapsers versus 25 future abstainers had lower fractional anisotropy (a measure
      of axonal organization and membrane integrity) in the corpus callosum and right
      stria terminalis/fornix, higher diffusivity in the genu of the corpus callosum,
      left and right stria terminalis/fornix, and lower diffusivity in left anterior
      corona radiata. These differences existed despite similar lifetime and recent
      drinking and smoking histories in the groups. Longer smoking duration in
      relapsers was associated with lower fractional anisotropy in right stria
      terminalis/fornix. The study identified specific microstructural biomarkers of
      alcohol relapse risk in adults, contributing to the definition of a
      neurobiological relapse risk profile in alcohol use disorder.

PMID- 30273794
TI  - Associations between depression, anxious arousal and manifestations of
      psychological inflexibility.
AB  - BACKGROUND AND OBJECTIVES: Psychological inflexibility exhibits across multiple
      facets of functioning, including thinking styles, personality, cognitive
      shifting, emotion, and physiology, with many of these manifestations showing
      associations with depression. As such, these facets might be part of an
      overarching latent construct of psychological inflexibility that explains
      associations with depression. We predicted that (1) five facets of inflexibility
      (perseverative thinking, personality rigidity, attention-shifting, negative
      emotional inertia, and low respiratory sinus arrhythmia reactivity) would load
      onto a unique latent construct of psychological inflexibility. Further, we
      hypothesized this latent construct of psychological inflexibility would be (2)
      significantly associated with higher depression; and (3) associated with
      depression to a greater extent than anxious arousal. METHODS: Seventy-five adult
      community participants completed measures assessing the five indices of
      inflexibility and self-report measures of depression and anxious arousal.
      RESULTS: Structural equation modeling identified a latent inflexibility construct
      reflected by perseverative thinking, personality rigidity, and emotional inertia,
      but did not include attention-shifting or RSA reactivity. The inflexibility
      construct was positively associated with depression and anxious arousal, but more
      strongly associated with depression than with anxious arousal. LIMITATIONS:
      Limitations included a small sample size, cross-sectional approach, and
      dimensional measures of depression and anxious arousal. CONCLUSIONS: Findings
      provide preliminary support that multiple facets of inflexibility may emerge from
      a broader overarching vulnerability for internalizing psychopathology. This
      overarching inflexibility construct may have stronger associations with
      depression than with anxious arousal.

PMID- 30273796
TI  - Reinforcement learning across the rat estrous cycle.
AB  - Reinforcement learning, the process by which an organism flexibly adapts behavior
      in response to reward and punishment, is vital for the proper execution of
      everyday behaviors, and its dysfunction has been implicated in a wide variety of
      mental disorders. Here, we use computational trial-by-trial analysis of data of
      female rats performing a probabilistic reward learning task and demonstrate that
      core computational processes underlying value-based decision making fluctuate
      across the estrous cycle, providing a neuroendocrine substrate by which gonadal
      hormones may influence adaptive behavior.

PMID- 30273795
TI  - Low-dose blue light irradiation enhances the antimicrobial activities of curcumin
      against Propionibacterium acnes.
AB  - Propionibacterium acnes (P. acnes) is an opportunistic infection in human skin
      that causes acne vulgaris. Antibiotic agents provide the effective eradication of
      microbes until the development of drug-resistant microbes. Photodynamic
      inactivation (PDI) is a non-antibiotic therapy for microbial eradication. In this
      study, the visible blue light (BL, lambdamax = 462 nm) was used to enhance the
      antimicrobial activities of curcumin, a natural phenolic compound. Individual
      exposure to curcumin or BL irradiation does not generate cytotoxicity on P.
      acnes. The viability of P. acnes was decreased significantly in 0.09 J/cm2 BL
      with 1.52 MUM of curcumin. Furthermore, the low-dose blue light irradiation
      triggers a series of cytotoxic actions of curcumin on P. acnes. The lethal
      factors of photolytic curcumin were investigated based on the morphology of P.
      acnes by SEM and fluorescent images. The membrane disruption of microbes was
      observed on the PDI against P. acnes. Chromatography and mass spectrometry
      techniques were also used to identify the photolytic metabolites. Curcumin could
      be photolysed into vanillin through BL irradiation, which presents a strong
      linear relationship in quantitation. Because the safety of blue light in
      mammalian cell has been proven, the photolytic curcumin treatment could support
      non-antibiotic therapy to eradicate P. acnes on clinical dermatology.

PMID- 30273797
TI  - Amygdalar activity predicts future incident diabetes independently of adiposity.
AB  - While it is established that psychosocial stress increases the risk of developing
      diabetes mellitus (DM), two key knowledge gaps remain: 1) the neurobiological
      mechanisms that are involved in mediating that risk, and 2) the role, if any,
      that adiposity plays in that mechanism. We tested the hypotheses that: 1)
      metabolic activity in the amygdala (AmygA), a key center involved in the
      neurobiological response to stress, associates with subsequent DM risk, and 2)
      this association is independent of adiposity. AmygA and adipose tissue volumes
      were measured, and serial blood assessments for DM were obtained in 232 subjects
      who underwent combined 18F-fluorodeoxyglucose positron emission
      tomography/computed tomography (18F-FDG-PET/CT) imaging. Higher baseline AmygA
      predicted subsequent, new-onset DM, independently of adiposity and other DM risk
      factors. Furthermore, higher adiposity only increased DM risk in the presence of
      higher AmygA. In a separate cross-sectional cohort, higher AmygA associated with
      higher insulin resistance. Accordingly, the current study shows, for the first
      time, that activity in a stress-responsive neural region predicts the onset of
      DM. Further, we observed that this neurobiological activity acts independently
      of, but also synergistically with adiposity to increase DM risk. These findings
      suggest novel therapeutic targets to help manage and possibly prevent DM.

PMID- 30273799
TI  - Keeping up with advances in axon guidance.
AB  - Twenty-five years after the discovery of the first chemotropic molecules for
      growing axons, what are the new findings? This review describes the latest
      progress made in our understanding of the molecular control of axonal guidance in
      the vertebrate nervous system. Special focus will be given to new molecular
      players, their source and location in vivo, and the role of membrane/receptor
      trafficking and RNA-based mechanisms in axon guidance cue signalling.

PMID- 30273798
TI  - The left temporal pole is a convergence region mediating the relation between
      names and semantic knowledge for unique entities: Further evidence from a
      "recognition-from-name" study in neurological patients.
AB  - Prior research has implicated the left temporal pole (LTP) as a critical region
      for naming semantically unique items, including famous faces, landmarks, and
      musical melodies. Most studies have used a confrontation naming paradigm, where a
      participant is presented with a stimulus and asked to retrieve its name. We have
      proposed previously that the LTP functions as a two-way, bidirectional
      convergence region brokering between conceptual knowledge and proper names for
      unique entities. Under this hypothesis, damage to the LTP should result in a "two
      way" impairment: (1) defective proper name retrieval when presented with a unique
      stimulus (as shown in prior work); and (2) defective concept retrieval when
      presented with a proper name. Here, we directly tested the second prediction
      using a "recognition-from-name" paradigm. Participants were patients with LTP
      damage, brain-damaged comparisons with damage outside the LTP, and healthy
      comparisons. Participants were presented with names of famous persons (e.g.,
      "Marilyn Monroe"), landmarks (e.g., "Leaning Tower of Pisa"), or melodies (e.g.,
      "Rudolph the Red-Nosed Reindeer") and were asked to provide conceptual knowledge
      about each. We found that individuals with damage to the LTP were significantly
      impaired at conceptual knowledge retrieval when given names of famous people and
      landmarks (but this finding did not hold for melodies). This outcome supports the
      theory that the LTP is a bidirectional convergence region for proper naming, but
      suggests that melody retrieval may rely on processes different from those
      supported by the LTP.

PMID- 30273800
TI  - Cross-sensitivity of psychiatric and behavioral side effects with antiepileptic
      drug use.
AB  - PURPOSE: To determine rates of cross-sensitivity of intolerable psychiatric and
      behavioral side effects (IPBSEs) among commonly used antiepileptic drugs (AEDs)
      in adult patients with epilepsy. METHODS: IPBSE was defined as a psychiatric or
      behavioral side effect attributed to AED use that led to a decrease in dose or
      cessation of an AED. Cross-sensitivity was calculated and was defined as the
      likelihood of developing IPBSE to a specific AED given IPBSE to another AED. Our
      sample consisted of 2312 adult patients that were prescribed 2 or more AEDs. Non
      AED confounders and were controlled for in all analyses. RESULTS: Among the 2312
      patients, 20.2% of patients who had taken at least 2 AEDs had IPBSE(s) attributed
      to at least one AED; 3.5% had IPBSE to two or more AEDs. History of treated
      depression and psychosis were found to be significant predictors (p < 0.001) of
      developing IPBSE and were controlled for in all AED-specific analyses. Cross
      sensitivity was seen between LEV and ZNS (p < 0.001). There was a significant
      increase in odds of experiencing IPBSE to LEV (41.5%; OR = 2.7; p < 0.001) or ZNS
      (22.1%; OR = 3.5; p < 0.001) given a patient had IPBSE to another AED compared to
      having no IPBSE to other AEDs (20.5% and 7.5%, respectively). CONCLUSION: History
      of depression and psychosis increased risk of developing IPBSE to AEDs. The
      probability of experiencing IPBSE increased for a patient taking LEV or ZNS if
      the patient experienced IPBSE to another AED. Our results may be clinically
      useful for predicting IPBSE associated with certain AEDs.

PMID- 30273801
TI  - Perspectives of psychiatric investigators and IRB chairs regarding benefits of
      psychiatric genetics research.
AB  - There is hope that psychiatric genetics inquiry will provide important insights
      into the origins and treatment of mental illness given the burden of these
      conditions. We sought to examine perspectives of psychiatric genetic
      investigators regarding the potential benefits of genetic research in general and
      the potential benefits of genetic research for the diagnosis and treatment of
      mental illnesses specifically. We compared investigator attitudes with those of
      chairs of Institutional Review Boards (IRBs) entrusted with evaluating the
      benefits and risks of human research studies. Two groups directly engaged with
      the conduct and oversight of psychiatric genetic research were examined
      (psychiatric investigators, n = 203; IRB Chairs, n = 183). Participants rated 15
      survey items regarding current and future benefits of general genetic research,
      possible benefits of psychiatric genetic research, and the importance to society
      of genetic vs. non-genetic research examining causes and treatments of illnesses.
      Investigators and IRB Chairs strongly endorsed the future benefits of general
      genetic research for society and for the health of individuals; compared to IRB
      Chairs, investigators were more positive about these benefits. Even after
      adjusting for demographic variables, psychiatric genetic investigators were
      significantly more optimistic about genetic research compared with IRB Chairs.
      Both groups were moderately optimistic about the possible benefits of genetic
      research related to mental illness. Greater optimism was seen regarding new or
      personalized medications for mental illnesses, as well as genetic predictive
      testing of mental illnesses. Greater precision and circumspection about the
      potential benefits of psychiatric genetic research are needed.

PMID- 30273802
TI  - Men are from Mars: The challenges of communicating as a male nursing student.
AB  - Male-female communication within nursing is often fraught with difficulties
      especially for male nurses as the try and assimilate themselves into a female
      dominated profession. It is clear that men and women possess different
      communication styles. Men tend to be forthright and to the point. Women on the
      other hand often view the world as a network of connections, as a negotiation for
      closeness and support and therefore centred on maintaining solidarity. The aim of
      this study was to explore the lived-experience of a group of male nursing
      students using Colaizzi's seven step data analysis within the phenomenological
      empirical framework. The central theme "Men are from Mars" identified two
      subthemes which included: calling a spade a spade in world of shovels and
      conscientious objector from the margins. Communication for the men in this study
      was difficult. The participants were sensitive of what and how they communicated
      could be misinterpreted which often left them feeling isolated. They were often
      perplexed how the female students spoke to and about each. The men on the other
      hand were open and honest in the way they communicated with each other; there was
      not misinterpretation the men knew exactly where they stood with each other.

PMID- 30273803
TI  - A collaborative approach to the implementation of a structured clinical handover
      tool (iSoBAR), within a hospital setting in metropolitan Western Australian: A
      mixed methods study.
AB  - The aim of this study was to determine the effectiveness of an education
      intervention for the implementation of the clinical handover tool iSoBAR, in an
      acute setting. A quantitative, descriptive survey design, using pre and post
      survey data before and after the implementation of an education intervention was
      used. Twenty nine nurses, doctors and allied health personnel employed at the
      study site participated in the study. The educational intervention consisted of
      an electronic presentation plus simulated video recorded exemplars of clinical
      handover. Outcome measures were the efficacy of the education intervention on the
      confidence of practitioners using the iSoBAR handover tool. Participants'
      understanding of the iSoBAR tool using Mann-Whitney U test was 2.54 pre
      intervention and 4.32 post-intervention. Confidence in using the tool also
      increased post educational intervention from 2.7 (pre-intervention) to 4.07 (post
      intervention). Focus groups identified several factors relating to the
      implementation of iSoBAR, creating two dominant themes: challenges concerning
      patient factors and change management processes and systems. Opportunities were
      identified: Practice enhancement, patient centred care, professional practice,
      and grassroots initiatives. The use of an interprofessional educational program
      increased the confidence and understanding of a range of health care
      practitioners when using the clinical handover tool iSoBAR.

PMID- 30273804
TI  - The effectiveness of short answers test papers in evaluating academic nursing
      programs: A review of the literature.
AB  - Short answer tests (SAT) are an assessment that examines nursing students'
      knowledge and can be used to evaluate expectations for student educational
      success. The purpose of this literature review is to combine the best available
      evidence as to whether short answer test papers meet nursing facility curricula
      learning outcomes. A literature review was performed consisting of data bases
      which included; ERIC, SCOPUS, CINAHL MEDLINE, COCHRANE LIBRARY and JOHANNA BIGGS
      INSTITUTE (JBI). The following keywords were used: Short answer test, written
      assessment, quiz, organisations, university, higher degree education, tertiary
      education, nursing, perceptions, attitude, opinions, thoughts, feeling and
      belief. The majority of studies demonstrated that short answer tests equip
      nursing students with the knowledge and critical thinking skills for the clinical
      setting. Three major themes were identified: the effects of increasing class
      sizes; authenticity and the validity of short answer tests. Short answer tests
      are commonly used in undergraduate nursing programs to evaluate students' level
      of knowledge which consists of their ability to critically analyse and problem
      solve. To maintain authenticity and validity of an assessment, there is a need
      for an evidence-based approach to their design to meet the core learning
      objectives within the curriculum.

PMID- 30273805
TI  - The mechanism of nanoparticle precipitation induced by electron irradiation in
      transmission electron microscopy.

PMID- 30273806
TI  - Direct investigation of charge transfer in neurons by electrostatic force
      microscopy.
AB  - Charge transfer plays fundamental roles in information transmission in cells,
      especially in neurons. To date, direct observation of charge propagation in
      neurons at nanometer level has not been achieved yet. Herein, a combined charge
      injection and Electrostatic Force Microscopy (EFM) detection approach is applied
      to directly study charge propagation and distribution at nanometer resolution in
      spines and synapses of hippocampal neurons. Charge density, charge mobility and
      membrane potential in neural signal transmission process through the spines of
      axons and dendrites of hippocampal neurons were investigated quantitatively.
      Postsynaptic densities (PSD) in spines of axons and dendrites were revealed and
      studied. The methods and results from present work provide insights into
      physiological activities and processes related with electrical properties in
      nervous system and other biological samples.

PMID- 30273807
TI  - A vibration analysis of a cracked micro-cantilever in an atomic force microscope
      by using transfer matrix method.
AB  - In this paper, the effects of crack size and its location have been investigated
      on the free vibration of an atomic force microscopy (AFM) cantilever applying
      transfer matrix method. By modeling the crack as a torsional spring and
      considering the boundary conditions at the contact point with sample's surface,
      the AFM cantilever vibration behavior has been formulated. Afterwards, the
      characteristic equation has been derived applying the transfer matrix. At the
      end, the effects of crack size and its location have been investigated on the
      flexural resonant frequency and sensitivity of the AFM cantilever. The results
      indicate that the frequency and sensitivity would be maximum when the crack is
      approximately in the middle of the cantilever. Growing the crack size can result
      in the variations of either resonant frequency or sensitivity especially for more
      stiff samples.

PMID- 30273808
TI  - Degradation of acetaminophen with ferrous/copperoxide activate persulfate:
      Synergism of iron and copper.
AB  - To enhance the advanced oxidation process based on persulfate, CuO was introduced
      into the Fe2+/PS system to achieve a synergistic effect between Fe and Cu.
      Results showed that Fe2+ was able to adsorb onto the CuO surface to form Fe(II)
      and further reduced Cu(II) into Cu(I), which can further release into the
      solution to participate in oxidation reactions. In this case, SO4.- can be
      generated via Fe2+ and Cu+ reactions with PS and .OH from Cu+ reaction with
      dissolved oxygen (DO). The degradation efficiency of APAP was studied under the
      optimal condition (initial pH 6.5, PS = 0.8 g L-1, Fe2+ = 0.7 mM, CuO = 0.3 g L
      1), and the results indicated that the Fe2+/CuO/PS system can achieve a higher
      degradation rate of APAP (92% within 90 min) rather than Fe2+/PS and CuO/PS
      system (79% and 10%). Quenching experiment was performed to verify the active
      radicals in the Fe2+/CuO/PS system. Sulfate and hydroxyl radicals were generated
      in the Fe2+/CuO/PS system. Besides, some critical factors, such as Fe2+
      concentration, catalyst dosage, PS concentration, initial pH (buffers and
      nonbuffers), and dissolved oxygen were evaluated in bath experiments. Results
      indicated that dissolved oxygen was essential in the Fe2+/CuO/PS system. APAP
      degradation experiments were conducted in surface water, and the intermediates
      were detected via GC-MS. The results indicated that the Fe2+/CuO/PS system is
      effective in the treatment of APAP in natural waters.

PMID- 30273809
TI  - Interfacing anaerobic digestion with (bio)electrochemical systems: Potentials and
      challenges.
AB  - For over a century, anaerobic digestion has been a key technology in stabilizing
      organic waste streams, while at the same time enabling the recovery of energy.
      The anticipated transition to a bio-based economy will only increase the quantity
      and diversity of organic waste streams to be treated, and, at the same time,
      increase the demand for additional and effective resource recovery schemes for
      nutrients and organic matter. The performance of anaerobic digestion can be
      supported and enhanced by (bio)electrochemical systems in a wide variety of
      hybrid technologies. Here, the possible benefits of combining anaerobic digestion
      with (bio)electrochemical systems were reviewed in terms of (1) process
      monitoring, control, and stabilization, (2) nutrient recovery, (3) effluent
      polishing, and (4) biogas upgrading. The interaction between microorganisms and
      electrodes with respect to niche creation is discussed, and the potential impact
      of this interaction on process performance is evaluated. The strength of
      combining anaerobic digestion with (bio)electrochemical technologies resides in
      the complementary character of both technologies, and this perspective was used
      to distinguish transient trends from schemes with potential for full-scale
      application. This is supported by an operational costs assessment, showing that
      the economic potential of combining anaerobic digestion with a
      (bio)electrochemical system is highly case-specific, and strongly depends on
      engineering challenges with respect to full-scale applications.

PMID- 30273810
TI  - The relationship between heparanase levels, thrombus burden and thromboembolism
      in patients receiving unfractionated heparin treatment for prosthetic valve
      thrombosis.
AB  - INTRODUCTION: Procoagulant activity of heparanase has been recently described in
      several arterial and venous thrombotic disorders. In this study, we aimed to
      investigate the role of heparanase with regard to thrombus burden,
      thromboembolism, and treatment success with unfractionated heparin (UFH) in
      patients with prosthetic valve thrombosis (PVT). METHODS: This study enrolled 79
      PVT patients who received UFH for PVT and 82 controls. Plasma samples which were
      collected from patients both at baseline and after the UFH treatment and from
      controls at baseline only, were tested for heparanase levels by heparanase enzyme
      linked immunosorbent assay. RESULTS: The PVT group included 18 obstructive and 61
      non-obstructive PVT patients who received UFH infusions for a median duration of
      15 (7-20) days. The UFH treatment was successful in 37 (46.8%) patients. Baseline
      heparanase levels were significantly higher in the patient group than in the
      controls [0.29 (0.21-0.71) vs. 0.25 (0.17-0.33) ng/mL; p = 0.002]. Baseline
      heparanase levels were significantly higher in obstructive PVT patients. There
      was a significant increase in heparanase levels after UFH treatment. Post-UFH
      heparanase levels were higher in patients who experienced treatment failure
      compared to successfully treated group. Baseline and post-UFH heparanase levels
      were significantly higher in patients with a thrombus area >=1 cm2 and with a
      recent history of thromboembolism. CONCLUSIONS: Increased heparanase levels may
      be one of the esoteric causes for PVT. UFH treatment may trigger an increase in
      heparanase levels which may affect the treatment success. Increased heparanase
      levels may be associated with high risk of thromboembolism and increased thrombus
      burden in PVT patients.

PMID- 30273811
TI  - Anti-PF4/heparin antibodies are increased in hospitalized patients with bacterial
      sepsis.
AB  - Heparin-induced thrombocytopenia (HIT) is caused by antibodies targeting platelet
      factor 4 (PF4)/heparin complexes. The immune response leading to HIT remains
      perplexing with many paradoxes. Unlike other drug induced reactions, anti
      PF4/heparin antibody generation does not follow the classic immunologic response.
      Research in murine models suggests that that there is close interplay among
      infection, PF4 and the immune system. We hypothesized there would be a relatively
      higher prevalence of anti-PF4/heparin antibodies in patients hospitalized for
      sepsis. We retrospectively examined anti-PF4/heparin antibody testing in 200 such
      patients. This included patients who had sepsis with bacteremia (n = 57), sepsis
      with fungemia (n = 7) and sepsis without bacteremia or fungemia (n = 136). For
      comparison, data from 50 patients without sepsis during the same time period was
      used. Results confirmed that patients hospitalized with sepsis have higher anti
      PF4/heparin antibody levels. The groups of patients having sepsis with
      bacteremia, and sepsis without bacteremia, had significantly higher OD than the
      control group without sepsis (p < 0.05). There was no significant difference
      between Gram negative and Gram positive bacteremia and antibody levels. This
      suggests that bacterial cell wall components of both classes have similar
      antigenicity. Interestingly, patients who had sepsis with fungemia had much lower
      antibody levels compared to those with sepsis and bacteremia, and sepsis without
      bacteremia or fungemia. Despite the small sample size for fungemia, this
      difference trended strongly towards statistical significance (p = 0.05). It would
      be interesting to investigate this further in a larger study or using in vitro
      studies. In summary, there is an increased prevalence of anti-PF4/heparin
      antibodies in patients hospitalized with bacterial but not fungal sepsis. These
      results indicate that bacterial infection has a role to play in preimmunization
      leading to anti-PF4/heparin antibody generation.

PMID- 30273812
TI  - Predictive and on-treatment monitoring biomarkers in advanced melanoma: Moving
      toward personalized medicine.
AB  - The treatment armamentarium for patients with metastatic melanoma has increased
      substantially over the past decade with the regulatory approval of targeted BRAF
      + MEK inhibitors and immune checkpoint inhibitors, which have vastly improved
      long-term outcomes. Recently, these advances have been rapidly translated to the
      high-risk adjuvant setting. Primary and acquired resistance to both immune and
      molecularly targeted agents, however, remains a challenge. Therefore, biomarkers
      predictive of response to therapy that can be assessed prior to initiation of
      treatment and early during the course of therapy are critical. Equally important
      is on-treatment biomarker monitoring that may predict the likelihood of treatment
      failure and disease relapse. This review will summarize recent advances in the
      understanding of biomarkers for patients with advanced melanoma, emphasizing
      emerging baseline predictive factors and on-treatment monitoring of biomarkers
      that aim to establish truly personalized treatment.

PMID- 30273813
TI  - Socioeconomic trends in school bullying among Finnish adolescents from 2000 to
      2015.
AB  - Bullying at school has far-reaching impacts on adolescent well-being and health.
      The aim of this study was to examine trends in bullying at school according to
      socioeconomic adversities among Finnish adolescents from 2000 to 2015. A
      population-based school survey was conducted biennially among 14-16-year-old
      Finns between 2000 and 2015 (n = 761,278). Distributions for bullying, being
      bullied and socioeconomic adversities were calculated. Associations between
      bullying involvement, time and socioeconomic adversities were studied using
      binomial logistic regression with results shown by odds ratios with 95%
      confidence intervals. At the population level, the likelihoods of bullying and
      being bullied varied only slightly between 2000 and 2015. Bullying and being
      bullied were associated with socioeconomic adversities (low parental education,
      not living with both parents and parental unemployment in the past year). Unlike
      in the general population, the likelihoods of bullying and being bullied
      increased markedly among adolescents with most socioeconomic adversities. The
      increased socioeconomic differences in bullying involvement observed in this
      study add to the mounting evidence of polarization of adolescent health and well
      being. Socioeconomic adversities should be considered in the prevention of
      bullying at school. In addition, socio-political measures are needed to decrease
      socioeconomic inequalities among Finnish adolescents.

PMID- 30273814
TI  - Exposure to domestic violence as abuse and neglect: Constructions of child
      maltreatment in daily practice.
AB  - Research finds that exposure to domestic violence can adversely affect the
      emotional, behavioral, and physical health of children. These effects have led
      some child advocates and policymakers in the United States to conclude that child
      exposure to domestic violence (CEDV) is a type of child maltreatment warranting
      state intervention. However, few states have defined CEDV as a type of
      maltreatment in statute and little is known about how child welfare agencies
      respond to allegations of CEDV in the absence of other safety threats. This study
      considers that CEDV itself might prompt an initial child welfare referral and may
      be construed by workers as a type of statutory maltreatment. Using a random
      sample (n = 295) of case records, this study analyzed one large child welfare
      agency's response to referrals alleging CEDV between 2011 and 2012. Findings
      indicate that CEDV itself did trigger investigation. At time of referral, workers
      used statutory maltreatment typologies to construe alleged CEDV as a type of
      maltreatment; however, CEDV was not consistently construed as a safety threat and
      few allegations were substantiated. Instead most families were referred to
      community-based domestic violence services. Findings indicate that CEDV was not
      consistently construed as a type of statutory maltreatment and infrequently
      resulted in ongoing child welfare services. Findings suggest that training is
      needed to help workers better assess CEDV-related safety threats. Findings also
      raise questions about what types of interventions are needed to protect children
      from domestic violence and which types of agencies are best positioned to deliver
      those interventions.

PMID- 30273815
TI  - Patterns of adversity and pathways to health among White, Black, and Latinx
      youth.
AB  - Research has demonstrated the negative impact of Adverse Childhood Experiences
      (ACEs) on long-term trajectories of mental and physical health. Yet existing
      literature on this topic is limited in its understanding of outcomes among youth
      samples, optimal measurement items and methods, and differences in adverse
      experiences across race/ethnicity. The current study used a person-centered
      approach to measure ACEs and their impact on youth health outcomes across three
      different racial/ethnic groups from a large national database. Patterns of
      exposure to adverse experiences among Black, Latinx, and White youth (N = 30,668,
      ages 12-17) were determined empirically using latent class analysis (LCA).
      Significant differences in class membership by demographic indicators (age,
      household income, sex) and concurrent health outcomes were identified. Different
      models emerged for Black (2 classes), Latinx (3 classes), and White youth (3
      classes). Older and lower-income youth were more likely to have experienced
      adversities, but there were no differences in adversity likelihood by sex.
      Additionally, racial/ethnic minority youth were at greater risk of experiencing
      higher levels of adversity, poverty, and poor health when compared to their White
      counterparts. Rather than occuring in meaningful clusters, adverse experiences
      among youth reflected a cumulative risk model such that classes were defined by
      the overall intensity of adverse experiences (i.e., low, moderate, high).
      Findings provide greater knowledge regarding the relationship between ACEs and
      health and future research directions to inform more targeted and culturally
      appropriate screening, prevention, and intervention programs.

PMID- 30273816
TI  - Capillary electrophoresis method for the determination of (R)-dapoxetine, (3S)-3
      (dimethylamino)-3-phenyl-1-propanol, (S)-3-amino-3-phenyl-1-propanol and 1
      naphthol as impurities of dapoxetine hydrochloride.
AB  - A capillary electrophoresis method was developed and validated for the
      determination of the purity of dapoxetine with regard to the related substances
      (3S)-3-amino-3-phenylpropan-1-ol, (3S)-3-(dimethylamino)-3-phenylpropan-1-ol, 1
      naphthol and the enantiomer (R)-dapoxetine. The separation was based on a dual
      selector system, which was optimized by a fractional factorial resolution V +
      design followed by a central composite face centered design with star distance 1
      and Monte Carlo simulations for defining the design space. The optimized
      background electrolyte consisted of a 50 mM sodium phosphate buffer, pH 6.3,
      containing 45 mg/mL sulfated gamma-cyclodextrin and 40.2 mg/mL 2,6-dimethyl-beta
      cyclodextrin. Separations were carried out in a 23.5/32 cm, 50 MUm fused-silica
      capillary employing a separation voltage of 9 kV at 15  degrees C. Following
      robustness testing using a Plackett-Burman design the method was validated
      according to the International Council on Harmonization guideline Q2(R1) in the
      range of 0.05-1.0% relative to the dapoxetine concentration. The method was
      applied to the analysis of drug substance and a commercial tablet. Data regarding
      the enantiomeric purity of dapoxetine obtained by the capillary electrophoresis
      assay were comparable to the data obtained by an enantioselective HPLC method.

PMID- 30273818
TI  - Development and validation of a method using ultra performance liquid
      chromatography coupled to tandem mass spectrometry for determination of
      zoledronic acid concentration in human bone.
AB  - A method for the extraction and quantification of zoledronic acid (ZA) from human
      bone was set up and validated. This method allowed the quantification of ZA from
      jawbone sequestrations of patients affected by bisphosphonate-related
      osteonecrosis of the jaw (BRONJ) associated with ZA treatment. The analyte was
      extracted from the bone tissues with phosphoric acid and derivatized using
      trimethylsilyl diazomethane (TMS-DAM). ZA tetramethyl phosphonate was then
      quantified by liquid chromatography coupled to tandem mass spectrometry (LC
      MS/MS), showing high accuracy, repeatability and selectivity. Lower limits of
      quantification and detection (LLOQ and LLQD) were 3.4 ng/mL and 1 ng/mg,
      respectively. This study fully described the analytical process for the
      determination of ZA in human bone sequestrations, representing a pivotal step for
      further biomedical research on ZA and BRONJ.

PMID- 30273817
TI  - Development of new methods for determination of bilirubin.
AB  - The ever-increasing demand for a sensitive, rapid and reliable method for
      determination of serum bilirubin level has been inciting the interest of the
      researchers to develop new methods for both laboratory set up and point of care
      applications. These efforts embrace measurement of different forms of bilirubin,
      such as, unconjugated (free and albumin bound) bilirubin, conjugated (direct)
      bilirubin, and total (both conjugated and unconjugated) bilirubin in the serum
      that may provide critical information useful for diagnosis of many diseases and
      metabolic disorders. Herein, an effort has been made to provide a broad overview
      on the subject starting from the conventional spectroscopy based analytical
      methods widely practiced in the laboratory setup along with the sophisticated
      instrument based sensitive methods suitable for determination of different forms
      of bilirubin to various portable low cost systems applicable in point of care
      (POC) settings. In all these discussions emphasis is given on the novel methods
      and techniques bearing potential to measure the bilirubin level in biological
      samples reliably with less technical complexity and cost. We expect that this
      review will serve as a ready reference for the researchers and clinical
      professionals working on the subject and allied fields.

PMID- 30273819
TI  - Effects of a leucine-enriched amino acid supplement on muscle mass, muscle
      strength, and physical function in post-stroke patients with sarcopenia: A
      randomized controlled trial.
AB  - OBJECTIVES: The aim of this study was to investigate the effects of a leucine
      enriched amino acid supplement on muscle mass, muscle strength, and physical
      function in post-stroke patients with sarcopenia. METHODS: We conducted an eight
      wk, two-parallel group intervention, randomized controlled, blinded outcome
      assessment among 44 post-stroke older patients with sarcopenia. Sarcopenia was
      defined as a loss of skeletal muscle mass and decreased muscle strength according
      to the Asian Working Group for Sarcopenia criteria. The intervention group (n =
      21) received a leucine-enriched amino acid supplement; the control group (n = 23)
      did not. Both groups performed low-intensity resistance training in addition to a
      post-stroke rehabilitation program. A primary outcome of physical function by
      using the motor domain of Functional Independence Measure (FIM), and secondary
      outcomes of appendicular muscle mass (skeletal muscle mass index [SMI]) measured
      via bioelectrical impedance analysis and muscle strength as handgrip strength
      were measured at baseline and at the end of the intervention. RESULTS: The FIM
      score increased significantly in both groups over time (P < 0.01), with
      significantly greater improvement in the intervention group than in the control
      group (P < 0.045). Handgrip strength also increased significantly over time (P
      <0.05), with significantly greater improvement in the intervention group (P <
      0.01). The SMI increased significantly in the intervention group but not in the
      control group over time, with significantly greater improvement in the
      intervention group (median estimated difference, 0.50 kg/m2; 95% confidence
      interval, 0.01-2.11). CONCLUSIONS: We demonstrated that an eight-wk intervention
      consisting of a leucine-enriched amino acid supplementation and low-intensity
      resistance training increased muscle mass, strength, and physical function in
      post-stroke patients with sarcopenia.

PMID- 30273820
TI  - Development, validity, and reproducibility of a semiquantitative food frequency
      questionnaire for the assessment of antioxidant vitamins intake in Lebanon.
AB  - OBJECTIVES: The growing interest in the possible role of antioxidant vitamins in
      many pathologies makes the methods of evaluating the intakes of these vitamins
      necessary. The food frequency questionnaire is the most widely used tool in
      epidemiologic studies and large-scale surveys to assess long-term nutritional
      exposure and to determine the usual intake of specific foods or nutrients. The
      aims of this study were to develop and investigate the validity and
      reproducibility of a semiquantitative food frequency questionnaire (SQFFQ) to
      evaluate the antioxidant vitamins intake in the Lebanese population and for use
      in clinical trials. METHODS: An SQFFQ draft was built with the major sources of
      vitamins with antioxidant properties initially selected from food that have the
      higher percentages of the daily value of vitamins A, C, and E; listed in the US
      Department of Agriculture tables. We used food intake data that were available
      through a 24-h dietary recall (3 weekdays and 1 weekend day) among a subsample of
      50 participants to complete the SQFFQ. We sought the major sources of the most
      frequently reported antioxidant vitamins, portion sizes, and percentages of the
      daily value of the major sources of these vitamins (developed by the US
      Department of Agriculture) to build a 34-item SQFFQ. The consumption frequency
      was coded as daily, weekly, monthly, or occasionally and one to three times or
      more. Five hundred Lebanese participants (the previous 50 who provided the 24 h
      dietary recall, along with 450 new participants) completed the questionnaire,
      whereas only 50 and 42 were accepted to be enrolled in the validity and
      reproducibility studies, respectively. To assess validity, the questionnaire was
      compared with the 24-h dietary recall performed on a subsample of 50 participants
      who already completed the SQFFQ. The reproducibility was assessed by comparing
      baseline SQFFQ with a second administration of the SQFFQ 3 to 5 wk later at the
      same dietetic clinic. RESULTS: The means of daily consumption of vitamins A, C,
      and E based on the SQFFQ and the 24 h data were as follows: Vitamin A: 252.5 +/-
      SD 958.9 versus 242.6 +/- SD 580.5 mcg of retinol activity equivalents (ug RAE),
      Vitamin C: 86.5 +/- SD 59.9 versus 85.5 +/- SD 56.2ug, and Vitamin E: 17 +/- SD
      7.2 versus 17.1 +/- SD 7.9ug. The Pearson correlation coefficients of the three
      vitamins between dietary intake estimates derived from the SQFFQ and 24-h data
      were, respectively, r = 0.83, 0.98, and 0.9; they were highly significant at P <
      0.001. One sample t tests and Bland-Altman plots confirmed this validity. The
      reproducibility of the SQFFQ was assessed using the Cronbach alpha index that
      measures reliability between different components (for vitamin A: 0.994, vitamin
      C: 0.998, and vitamin E: 0.975). The correlation matrix (interitem correlation)
      showed that all elements were highly correlated (r > 0.4) and even close to 1
      (for vitamin A = 0.989, vitamin C = 0.995, and vitamin E = 0.95). CONCLUSIONS: In
      this study, we described the development of an SQFFQ. Based on the results, we
      found the SQFFQ to be valid and reproducible to assess intake of antioxidant
      vitamins in Lebanese adults.<END ABSTRACT>.

PMID- 30273821
TI  - Peripheral interleukin-6 levels and working memory in non-obese adults: A post
      hoc analysis from the CALERIE study.
AB  - OBJECTIVES: This analysis aimed to investigate the association among interleukin
      6 (IL-6) levels, caloric intake, and working memory and to explore the potential
      mediators of these associations using the public dataset from the Comprehensive
      Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) clinical
      trial. METHODS: The CALERIE study was designed to evaluate the effects of 2 y of
      prolonged caloric restriction in humans. Individuals were randomized to caloric
      restriction (CR; n = 145) or an ad libitum diet (AL; n = 75) for 2 y. The outcome
      measures used herein were spatial working memory tests (i.e., total number of
      errors and strategy). Generalized estimating equations were used to assess the
      effects of treatment, time, and potential moderators (e.g., sleep and physical
      activities). RESULTS: At baseline, there was an effect of hours of sleep, alcohol
      intake, and physical activities (i.e., mean total metabolic equivalent of task
      hours per day [MET-hours/day]) on IL-6 levels. The association between IL-6 and
      energy intake was moderated by MET-hours/day. The longitudinal analysis indicated
      that there was an effect of time, but not of treatment, on IL-6 levels, with
      decreasing values in both the CR and AL groups. Changes in IL-6 levels were
      associated with changes in working memory performance, but there were no between
      group (i.e., CR vs. AL) differences. CONCLUSIONS: We observed an association
      between changes in IL-6 levels and improvement in spatial working memory tests.
      IL-6 was associated with higher caloric consumption, poorer sleep quality, and
      lower levels of physical activity.

PMID- 30273822
TI  - Ingestion of soy protein isolate attenuates eccentric contraction-induced force
      depression and muscle proteolysis via inhibition of calpain-1 activation in rat
      fast-twitch skeletal muscle.
AB  - OBJECTIVE: Eccentric contraction (ECC) is a contraction in which skeletal muscles
      are stretched while contracting. The aim of this study was to determine how
      ingestion of soy protein isolate (SPI) or animal-based proteins affect force
      deficit, calpain activation, and proteolysis of calcium ion (Ca2+)-regulatory
      proteins in rat fast-twitch muscles subjected to ECC. METHODS: In the first
      experiment, male Wistar rats were randomly assigned to a control and an SPI
      group, which were fed a 20% casein and a 20% SPI diet, respectively, for 28 d
      before the ECC protocol. Anterior crural muscles underwent 200 repeated ECCs and
      were excised 3 d later. In the second experiment, half of the SPI rats were given
      water containing NG-nitro-l-arginine-methyl ester (L-NAME), an inhibitor of
      nitric oxide synthase, for 3 d of recovery after ECC. RESULTS: SPI ingestion
      attenuated ECC-induced force deficit, proteolysis of Ca2+-regulatory proteins,
      and autolysis of calpain-1. Co-ingestion of L-NAME inhibited SPI-associated
      increases in nitrite and nitrate levels and negated the force recovery effects of
      SPI. CONCLUSION: These results suggest that SPI ingestion inhibits ECC-elicited
      force deficit and proteolysis of Ca2+ regulatory proteins, which is caused by
      inhibited activation of calpain-1 via increased nitric oxideproduction.

PMID- 30273823
TI  - Dietary intake of magnesium and the risk of epilepsy in middle-aged and older
      Finnish men: A 22-year follow-up study in a general population.
AB  - OBJECTIVES: Magnesium may play an important role in the prevention or treatment
      of epilepsy. We aimed to examine the association between dietary intake of
      magnesium and the incidence of epilepsy in middle-aged Finnish men in a
      prospective setting. As a secondary analysis, we also considered a possible
      association between dietary intake of magnesium and inflammation in subjects with
      epilepsy. METHODS: The study included 2442 men, ages 42 to 60 y, from the
      prospective Kuopio Ischaemic Heart Disease Risk Factor Study who were free of
      epilepsy at baseline between 1984 and 1989. Dietary intake of magnesium was
      assessed with a 4-d food record. The hospital discharge diagnosis of epilepsy was
      used as an outcome variable. RESULTS: During the average follow-up period of 22.4
      y, 74 men (3%) developed epilepsy. Those who followed the recommended dietary
      intake (>350 mg/d) of magnesium had a lower risk of epilepsy (hazard ratio [HR]:
      0.52; confidence interval [CI], 0.28-0.99; P = 0.045) after multivariate
      adjustments. However, the risk was not significant after adjustment for C
      reactive protein (CRP). We also found that CRP concentration was directly
      associated with the risk of epilepsy (HR: 1.24; CI, 1.00-1.54; P = 0.048). This
      association was attenuated after adjustment for dietary intake of magnesium and
      no longer significantly associated with the risk of epilepsy (HR: 1.22; CI, 0.99
      1.52; P = 0.07). CONCLUSIONS: A higher dietary intake of magnesium was associated
      with lower incident epilepsy, and this association was slightly mediated by CRP.
      Further studies are required to identify the potential mechanisms.

PMID- 30273824
TI  - Sharing data on DNA transfer, persistence, prevalence and recovery: Arguments for
      harmonization and standardization.
AB  - Sharing data between forensic scientists on DNA transfer, persistence, prevalence
      and recovery (TPPR) is crucial to advance the understanding of these issues in
      the criminal justice community. We present the results of a collaborative
      exercise on reporting forensic genetics findings given activity level
      propositions. This exercise outlined differences in the methodology that was
      applied by the participating laboratories, as well as limitations to the use of
      published data on DNA TPPR. We demonstrate how publication of experimental
      results in scientific journals can be further improved to allow for an adequate
      use of these data. Steps that can be taken to share and use these data for
      research and casework purposes are outlined, and the prospects for future sharing
      of data through publicly accessible databases are discussed. This paper also
      explores potential avenues to proceed with implementation and is intended to fuel
      the discussion on sharing data pertaining to DNA TPPR issues. It is further
      suggested that international standardization and harmonization on these topics
      will benefit the forensic DNA community as it has been achieved in the past with
      the harmonization of STR typing systems.

PMID- 30273825
TI  - Simultaneous application of predictive model and least cost formulation can
      substantially benefit biorefineries outside Corn Belt in United States: A case
      study in Florida.
AB  - Previously, a predictive model was developed to identify optimal blends of
      expensive high-quality and cheaper low-quality feedstocks for a given
      geographical location that can deliver high sugar yields. In this study, the
      optimal process conditions were tested for application at commercially-relevant
      higher biomass loadings. We observed lower sugar yields but 100% conversion to
      ethanol from a blend that contained only 20% high-quality feedstock. The impact
      of applying this predictive model simultaneously with least cost formulation
      model for a biorefinery location outside of the US Corn Belt in Lee County,
      Florida was investigated. A blend ratio of 0.30 EC, 0.45 SG, and 0.25 CS in Lee
      County was necessary to produce sugars at high yields and ethanol at a capacity
      of 50 MMGY. This work demonstrates utility in applying predictive model and LCF
      to reduce feedstock costs and supply chain risks while optimizing for product
      yields.

PMID- 30273826
TI  - The changes in carbon, nitrogen components and humic substances during organic
      inorganic aerobic co-composting.
AB  - In this article, the changes in carbon, nitrogen components, and humic substances
      during organic-inorganic aerobic co-composting, with adding biochar as an
      additive or not, were studied. Results showed that adding a certain amount of
      inorganic fertilizers had no adverse effects on the compost fermentation process.
      Biochar enhanced the temperature, pH, oxygen content in the compost piles and
      ultimately hastened the fermentation process. Biochar contributed to the
      decomposition of hemicellulose, cellulose, lignin and promoted compost
      humification. Adding biochar increased the contents of acid hydrolysis nitrogen,
      amino acid nitrogen, amino sugar nitrogen, unidentified organic nitrogen and
      decreased the content of ammonia organic nitrogen thus improved nitrogen
      transformation and reduced nitrogen loss. The addition of biochar increased the
      nutrients contents in mature composts. The amendment of 10-15% biochar by weight
      as an additive would be optimum for the co-composting of organic-inorganic
      materials. These results contributed to produce value-added composting
      fertilizers.

PMID- 30273827
TI  - Co-metabolic enhancement of 1H-1,2,4-triazole biodegradation through
      nitrification.
AB  - Due to highly recalcitrant nature of 1H-1,2,4-triazole (TZ), the conventional
      biological process is quite ineffective for TZ removal from wastewater. In this
      study, co-metabolic enhancement of TZ biodegradation through nitrification was
      investigated in an activated sludge reactor. The link between enhanced TZ
      degradation and nitrification was established through highly efficient removal of
      TZ, TOC as well as dissolved organic matter with the supplement of NH4+. A new co
      metabolic degradation pathway of TZ was proposed based on the identification of
      five co-metabolic intermediates, including 2,4-dihydro-[1,2,4]triazol-3-one and
      [1,2,4]triazolidine-3,5-dione. High-throughput sequencing analysis suggested the
      significant improvement of microbial community in the co-metabolic system in
      terms of richness, abundance and uniformity. Functional species related to
      nitrification and biodegradation was enriched with the supplement of NH4+,
      confirming the key role of nitrification. This study demonstrated that
      nitrification-assisted co-metabolism had a promising potential for the removal of
      recalcitrant contaminants such as TZ from wastewater.

PMID- 30273828
TI  - Characteristics of acidogenic fermentation for volatile fatty acid production
      from food waste at high concentrations of NaCl.
AB  - This study explored the effects of NaCl on volatile fatty acid (VFA) production
      from food waste by acidogenic fermentation. The production and composition of
      VFAs, and the microbial community in acidogenic fermentation were investigated at
      four different NaCl concentrations: 10, 30, 50, and 70 g/L, and at 0 g/L
      (control). The highest VFA production was 0.542 g/g dry weight of food waste at
      10 g/L NaCl, and about 23% lower but still high at 70 g/L NaCl. Interestingly, as
      NaCl concentration increased, the residence time of lactic acid in the reactor
      increased, and the maximum production also increased. The type of acidogenic
      fermentation also changed from butyric acid to propionic acid as the NaCl
      concentration increased. Microbial community analysis showed that a large number
      of propionibacteria were present at the end of fermentation, indicating their
      high tolerance to NaCl.

PMID- 30273829
TI  - Early disruption of parvalbumin expression and perineuronal nets in the
      hippocampus of the Tg2576 mouse model of Alzheimer's disease can be rescued by
      enriched environment.
AB  - Recent findings show that parvalbumin (PV) interneuron function is impaired in
      Alzheimer's disease (AD), and that this impairment in PV function can be linked
      to network dysfunction and memory deficits. PV cells are often associated with a
      specific extracellular matrix, the perineuronal net (PNN). PNNs are believed to
      protect PV cell integrity, and whether the amyloidopathy affects PNNs remains
      unclear. Here, we evaluated the number of PV cells with and without PNNs in the
      hippocampus of the Tg2576 mouse model of AD at different stages of the disease.
      We show a deficit of PV+ and/or PV+/PNN+ cells in the areas CA1, CA2, and CA3 in
      Tg2576 as young as 3 months of age. Importantly, transient exposure to an
      enriched environment, which has proven long-lasting beneficial effects on memory
      in AD subjects, rescues the PV/PNN cell number deficits. We conclude that
      cognitive improvements induced by enriched environment in AD mouse models could
      be supported by a remodeling of hippocampal PV cell network and their PNNs.

PMID- 30273830
TI  - Sleep and circadian abnormalities precede cognitive deficits in R521C FUS knockin
      rats.
AB  - Mutations in fused in sarcoma (Fus) cause familial amyotrophic lateral sclerosis
      (ALS) and occasionally frontotemporal dementia. Here we report the establishment
      and characterization of a novel knockin (KI) rat model expressing a Fus point
      mutation (R521C) via CRISPR/Cas9. The mutant animals developed adult-onset
      learning and memory behavioral deficits, with reduced spine density in
      hippocampal neurons. Remarkably, sleep-wake cycle and circadian abnormalities
      preceded the onset of cognitive deficit. RNA-seq study further demonstrated
      altered expression of some key sleep and circadian regulators, such as
      orexin/hypocretin receptor type 2 and casein kinase 1 epsilon, in the mutant
      rats. Therefore, we have established a rodent model expressing physiological
      level of a pathogenic mutant FUS, and we found cognitive impairment as a main
      behavioral deficit at mid age. Furthermore, we have revealed a new role of FUS in
      sleep and circadian regulation and demonstrated that functional change in FUS
      could cause sleep-wake and circadian disturbance as early symptoms.

PMID- 30273831
TI  - 3D imaging system for respiratory monitoring in pediatric intensive care
      environment.
AB  - Assessment of respiratory activity in pediatric intensive care unit allows a
      comprehensive view of the patient's condition. This allows the identification of
      high-risk cases for prompt and appropriate medical treatment. Numerous research
      works on respiration monitoring have been conducted in recent years. However,
      most of them are unsuitable for clinical environment or require physical contact
      with the patient, which limits their efficiency. In this paper, we present a
      novel system for measuring the breathing pattern based on a computer vision
      method and contactless design. Our 3D imaging system is specifically designed for
      pediatric intensive care environment, which distinguishes it from the other
      imaging methods. Indeed, previous works are mostly limited to the use of
      conventional video acquisition devices, in addition to not considering the
      constraints imposed by intensive care environment. The proposed system uses depth
      information captured by two (Red Green Blue-Depth) RGB-D cameras at different
      view angles, by considering the intensive care unit constraints. Depth
      information is then exploited to reconstruct a 3D surface of a patient's torso
      with high temporal and spatial resolution and large spatial coverage. Our system
      captures the motion information for the top of the torso surface as well as for
      its both lateral sides. For each reconstruction, the volume is estimated through
      a recursive subdivision of the 3D space into cubic unit elements. The volume
      change is then calculated through a subtraction technique between successive
      reconstructions. We tested our system in the pediatric intensive care unit of the
      Sainte-Justine university hospital center, where it was compared to the gold
      standard method currently used in pediatric intensive care units. The performed
      experiments showed a very high accuracy and precision of the proposed imaging
      system in estimating respiratory rate and tidal volume.

PMID- 30273832
TI  - Adaptive fusion of texture-based grading for Alzheimer's disease classification.
AB  - Alzheimer's disease is a neurodegenerative process leading to irreversible mental
      dysfunctions. To date, diagnosis is established after incurable brain structure
      alterations. The development of new biomarkers is crucial to perform an early
      detection of this disease. With the recent improvement of magnetic resonance
      imaging, numerous methods were proposed to improve computer-aided detection.
      Among these methods, patch-based grading framework demonstrated state-of-the-art
      performance. Usually, methods based on this framework use intensity or grey
      matter maps. However, it has been shown that texture filters improve
      classification performance in many cases. The aim of this work is to improve
      performance of patch-based grading framework with the development of a novel
      texture-based grading method. In this paper, we study the potential of multi
      directional texture maps extracted with 3D Gabor filters to improve patch-based
      grading method. We also proposed a novel patch-based fusion scheme to efficiently
      combine multiple grading maps. To validate our approach, we study the optimal set
      of filters and compare the proposed method with different fusion schemes. In
      addition, we also compare our new texture-based grading biomarker with state-of
      the-art methods. Experiments show an improvement of AD detection and prediction
      accuracy. Moreover, our method obtains competitive performance with 91.3% of
      accuracy and 94.6% of area under a curve for AD detection.

PMID- 30273833
TI  - Bioinspired silica-infiltrated zirconia bilayers: Strength and interfacial
      bonding.
AB  - Conventionally veneered zirconia restorations are susceptible to chipping and
      spalling of the veneering material. The novel translucent zirconias were
      developed to overcome such issues, although layered zirconia restorations can be
      re-designed to improve mechanical performance. Thus, the aim of this study was to
      analyze the strength and structural reliability of zirconia bilayers using
      conventional (porcelain ceramic under tensile stress) and bioinspired (zirconia
      under tensile stress) configurations. Sol-gel silica infiltration served as a
      smooth transition between the zirconia and veneering porcelain. Failure mode and
      interfacial adhesive mechanism were analyzed using scratch test and interfacial
      indentation. Bilayered specimens were produced for biaxial flexural testing with
      Y-TZP and pressed ceramic, which were further divided into four groups (n = 30):
      Conventional (C), Infiltrated conventional (IC), Bioinspired (B) and Infiltrated
      bioinspired (IB). The results of biaxial flexural strength tests were analyzed by
      Weibull analysis (95% CI) for determination of the Weibull modulus (m). The
      infiltration layer was characterized by XRD and SEM, FEG-SEM and EDS. The
      bioinspired infiltrated group was the most reliable (m = 9.59), although the fine
      damage of veneered conventional (conventional) zirconia demonstrated its superior
      resistance to scratching and debonding. Therefore, the filling of superficial
      defects by zirconia silicate demonstrated the need for mechanical retention for
      better porcelain adhesion.

PMID- 30273835
TI  - Bioengineered stem cell membrane functionalized nanocarriers for therapeutic
      targeting of severe hindlimb ischemia.
AB  - Bioengineering strategies to enhance the natural targeting function of
      nanocarriers would expand their therapeutic applications. Here, we designed
      bioengineered stem cell membrane-functionalized nanocarriers (BSMNCs) harboring C
      X-C chemokine receptor type 4 (CXCR4) to achieve robust targeting and also to
      increase their retention time in ischemic tissue. Stem cell membrane coated
      nanocarrier (SMNCs) or poly (lactic-co-glycolic acid) (PLGA) nanocarriers (PNCs)
      and BSMNCs were prepared by functionalizing PNCs with human adipose-derived stem
      cells (hASCs) membranes and hASCs engineered to overexpress CXCR4-receptor,
      respectively. The functionalization of PNCs with stem cell membranes derived from
      hASCs significantly enhance the nanocarrier penetration across endothelial cell
      barrier compare to PNCs. In addition, stem cell membrane functionalization on
      PNCs also significantly decreased the nanoparticles uptake in J774 (murine) and
      THP (human) macrophages respectively from 84% to 76%-29% and 24%. Interestingly,
      BSMNCs showed much higher level of accumulation in ischemic tissue than SMNCs.
      Systemic retro-orbital injection of BSMNCs loaded with VEGF into mice with
      hindlimb ischemia resulted substantially enhancement of blood reperfusion, muscle
      repair, and limb salvage compared to animals treated with SMNCs loaded with
      similar concentration of VEGF. The reported strategy could be used to create
      biocompatible and custom-tailored biomimetic nanoparticles with various hybrid
      functionalities, which may overcome the limitations of current nanoparticle-based
      therapeutic and imaging platforms.

PMID- 30273834
TI  - Spatially controlled assembly of affinity ligand and enzyme cargo enables
      targeting ferritin nanocarriers to caveolae.
AB  - One of the goals of nanomedicine is targeted delivery of therapeutic enzymes to
      the sub-cellular compartments where their action is needed. Endothelial caveolae
      derived endosomes represent an important yet challenging destination for
      targeting, in part due to smaller size of the entry aperture of caveolae (ca. 30
      50 nm). Here, we designed modular, multi-molecular, ferritin-based nanocarriers
      with uniform size (20 nm diameter) for easy drug-loading and targeted delivery of
      enzymatic cargo to these specific vesicles. These nanocarriers targeted to
      caveolar Plasmalemmal Vesicle-Associated Protein (Plvap) deliver superoxide
      dismutase (SOD) into endosomes in endothelial cells, the specific site of influx
      of superoxide mediating by such pro-inflammatory signaling as some cytokines and
      lipopolysaccharide (LPS). Cell studies showed efficient internalization of Plvap
      targeted SOD-loaded nanocarriers followed by dissociation from caveolin
      containing vesicles and intracellular transport to endosomes. The nanocarriers
      had a profound protective anti-inflammatory effect in an animal model of LPS
      induced inflammation, in agreement with the characteristics of their endothelial
      uptake and intracellular transport, indicating that these novel, targeted
      nanocarriers provide an advantageous platform for caveolae-dependent delivery of
      biotherapeutics.

PMID- 30273836
TI  - Pentamethinium salts as ligands for cancer: Sulfated polysaccharide co-receptors
      as possible therapeutic target.
AB  - A series of pentamethinium salts with benzothiazolium and indolium side units
      comprising one or two positive charges were designed and synthesized to determine
      the relationships among the molecular structure, charge density, affinity to
      sulfated polysaccharides, and biological activity. Firstly, it was found that the
      affinity of the pentamethinium salts to sulfated polysaccharides correlated with
      their biological activity. Secondly, the side heteroaromates displayed a strong
      effect on the cytotoxicity and selectivity towards cancer cells. Finally, doubly
      charged pentamethinium salts possessing benzothiazolium side units exhibited
      remarkably high efficacy against a taxol-resistant cancer cell line.

PMID- 30273837
TI  - Pharmacokinetics, tissue distribution and plasma protein binding study of SM-1, a
      novel PAC-1 derivative.
AB  - As a PAC-1 derivative, SM-1 exhibts a promising antitumour property. To better
      understand the relationship between the drug concentrations and pharmacological
      effects, both liquid chromatography coupled with tandem mass spectrometry and
      high performance liquid chromatography methods were developed and validated in
      the work. Those methods were then applied to the pharmacokinetics (PK), tissue
      distribution and plasma protein binding (PPB) studies of SM-1. As a results, the
      proposed methods were demonstrated to be accurate, precise and stable for the
      analysis of the SM-1 in plasma and tissue samples. Meanwhile, the PK parameters
      of SM-1 showed that SM-1 had good PK properties. SM-1 had good absorption in the
      body, with 59.01% of the absolute bioavailability in rats and 55.63% of that in
      dogs. SM-1 rapidly distributed to all tissues, with the highest distribution in
      the lung and less in the brain and muscle. The PPB rates in rat plasma, dog
      plasma, and human plasma were 91.1%, 91.2%, and 90.7%, respectively. These good
      PK properties will contribute SM-1 to be a promising anti-tumour candidate. These
      results also provide insights into the further pharmacological investigation of
      SM-1.

PMID- 30273838
TI  - Peak window correlation method for drug screening using Raman spectroscopy.
AB  - Modern portable and hand-held Raman spectrometers that recently have become
      widespread in drug quality screening have good reproducibility and are able to
      detect small concentrations of substances in mixtures of several components or
      distinguish compounds similar in structure and having minimal differences in
      spectrum with appropriate mathematical processing methods. Among other spectrum
      comparison approaches, the peak search at their location is the most important
      task of spectral imaging of the studied samples. In this work, the Raman spectra
      of liquid drugs involved in the governmental non-destructive quality screening
      program performed by 8 mobile laboratories equipped with Raman spectrometers with
      uncooled detector and a 532 nm laser were compared with reference sample spectra
      using the peak windows correlation (PWC) algorithm developed in this work by
      authors. The proposed method provides accurate identification, detection of
      composition changes, and presence of foreign components in drugs formulations
      even if their contribution to the overall signal is negligible. The spectral
      correlation method called hit-quality index (HQI) method conventionally used for
      such portable spectrometers was specified as comparative method.

PMID- 30273839
TI  - Lysosomal exocytosis of ATP is coupled to P2Y2 receptor in marginal cells in the
      stria vascular in neonatal rats.
AB  - Adenosine triphosphate (ATP) is stored as lysosomal vesicles in marginal cells of
      the stria vascular in neonatal rats, but the mechanisms of ATP release are
      unclear. Primary cultures of marginal cells from 1-day-old Sprague-Dawley rats
      were established. P2Y2 receptor and inositol 1,4,5-trisphosphate (IP3) receptor
      were immunolabelled in marginal cells of the stria vascular. We found that 30 MUM
      ATP and 30 MUM uridine triphosphate (UTP) evoked comparable significant increases
      in the intracellular Ca2+ concentration ([Ca2+]i) in the absence of extracellular
      Ca2+, whereas the response was suppressed by 100 MUM suramin, 10 MUM 1-(6-(17beta
      3-methoxyester-1,3,5(10)-trien-17-yl)amino)-hexyl)-1H-pyrrole-2,5-dione(U-73122),
      100 MUM 2-aminoethoxydiphenyl borate (2-APB) and 5 MUM thapsigargin (TG), thus
      indicating that ATP coupled with the P2Y2R-PLC-IP3 pathway to evoke Ca2+ release
      from the endoplasmic reticulum (ER). Incubation with 200 MUM Gly-Phe-beta
      naphthylamide (GPN) selectively disrupted lysosomes and caused significant
      increases in [Ca2+]I; this effect was partly inhibited by P2Y2R-PLC-IP3 pathway
      antagonists. After pre-treatment with 5 MUM TG, [Ca2+]i was significantly lower
      than that after treatment with P2Y2R-PLC-IP3 pathway antagonists under the same
      conditions, thus indicating that lysosomal Ca2+ triggers Ca2+ release from ER
      Ca2+ stores. Baseline [Ca2+]i declined after treatment with the Ca2+ chelator 50
      MUM bis-(aminophenolxy) ethane-N,N,N',N'-tetra-acetic acid acetoxyme-thyl ester
      (BAPTA-AM) and 4 IU/ml apyrase. 30 MUM ATP decrease of the number of quinacrine
      positive vesicles via lysosome exocytosis, whereas the number of lysosomes did
      not change. However, lysosome exocytosis was significantly suppressed by pre
      treatment with 5 MUM vacuolin-1. Release of ATP and beta-hexosaminidase both
      increased after treatment with 200 MUM GPN and 5 MUM TG, but decreased after
      incubation with 50 MUM BAPTA-AM, 4 IU/ml apyrase and 5 MUM vacuolin-1. We suggest
      that ATP triggers Ca2+ release from the ER, thereby contributing to secretion of
      lysosomal ATP via lysosomal exocytosis. Lysosomal stored Ca2+ triggers Ca2+
      release from the ER directly though the IP3 receptors, and lysosomal ATP evokes
      Ca2+ signals indirectly via the P2Y2R-PLC-IP3 pathway.

PMID- 30273841
TI  - Patient-reported outcomes in patients with relapsing forms of MS switching to
      teriflunomide from other disease-modifying therapies: Results from the global
      Phase 4 Teri-PRO study in routine clinical practice.
AB  - BACKGROUND: Patient-reported outcomes (PROs) can assist clinicians in
      understanding the impact of disease-modifying therapy (DMT) on the daily lives of
      patients with multiple sclerosis (MS). With an increased number of DMTs becoming
      available, patients are now switching treatments more frequently in clinical
      practice. The effects of switching DMTs on a patient's daily life and their
      disease course may be reflected in PROs. The global, multicenter, open-label,
      phase 4 Teri-PRO study (NCT01895335), which was conducted in routine clinical
      practice, previously showed statistically and clinically significant increases in
      patient-reported treatment satisfaction in patients switching to teriflunomide
      from other DMTs. The impact of switching to teriflunomide from other DMTs on
      treatment satisfaction and a range of additional PROs was also evaluated.
      METHODS: Patients with relapsing forms of MS (N = 1000) received teriflunomide
      for 48 weeks per local labeling. Outcomes assessed in this analysis included
      treatment satisfaction (as measured by Treatment Satisfaction Questionnaire for
      Medication [Version 1.4]), disability worsening (as measured using the Expanded
      Disability Status Scale [EDSS] score, the Patient-Determined Disease Steps scale,
      and the Multiple Sclerosis Performance Scale), cognition (as measured using the
      Symbol Digit Modalities Test [SDMT]), treated relapses, quality of life (as
      measured by the Multiple Sclerosis International Quality of Life [MusiQoL]
      questionnaire and the Stern Leisure Activity Scale), and safety/tolerability over
      the course of the study in the subgroup of patients switching to teriflunomide
      from another DMT (n = 594). RESULTS: Patients reported significant improvements
      in treatment satisfaction scores following the switch to teriflunomide regardless
      of the reason for treating with teriflunomide (Global Satisfaction, disease
      worsening: baseline, 46.0, Week 48, 65.1; convenience: baseline, 57.4, Week 48,
      72.4; intolerance: baseline, 50.9, Week 48, 71.1; side effects: baseline, 49.7,
      Week 48, 67.2; P < 0.0001 in all comparisons). These patients also showed
      improvement or stability in PROs evaluating disability worsening, cognition, and
      quality of life (EDSS: baseline, 3.1, Week 48, 3.0; SDMT: baseline, 0.975, Week
      48, 0.978; MusiQoL: baseline, 67.5, Week 48, 69.5). The safety and tolerability
      profile of teriflunomide was consistent with that observed in other teriflunomide
      clinical trials. CONCLUSION: This analysis of the Teri-PRO study demonstrates the
      value of switching to teriflunomide from other DMTs in a real-world, clinical
      practice setting. The high levels of treatment satisfaction associated with
      teriflunomide in Teri-PRO may lead to improved adherence and thus improved
      outcomes.

PMID- 30273840
TI  - Draining the pond and catching the fish: Uncovering the ecosystem of auditory
      verbal hallucinations.
AB  - The various models proposed for the mediation of auditory verbal hallucinations
      (AVH) implicate a considerable number of brain areas and mechanisms. To establish
      which of those mechanisms are actually involved in the mediation of AVH, we
      developed a novel method to analyze functional MRI data, which allows for the
      detection of the full network of mutually interacting brain states, and the
      identification of those states that are relevant to the mediation of AVH, while
      applying a minimum number of preconceived assumptions. This method is comparable
      to the draining of a pond to lay bare the full ecosystem that affects the
      presence of a particular fish species. We used this model to analyze the fMRI
      data of 85 psychotic patients experiencing AVH. The data were decomposed into 98
      independent components (ICs) representing all major functions active in the brain
      during scanning. ICs involved in mediating AVH were identified by associating
      their time series with the hallucination time series as provided by subjects
      within the scanner. Using graph theory, a network of interacting ICs was created,
      which was clustered into IC modules. We used causal reasoning software to
      determine the direction of links in this network, and discover the chain of
      events that leads to the conscious experience of hallucinations. Hallucinatory
      activity was linked to three of the seven IC clusters and 11 of the 98 ICs. ICs
      with the most influential roles in producing AVH-related activity were those
      within the so-called salience network (comprising the anterior cingulate gyrus,
      right insula, Broca's homologue, premotor cortex, and supramarginal gyrus).
      Broca's area and the cerebellar regions were significantly, but more distantly
      involved in the mediation of AVH. These results support the notion that AVH are
      largely mediated by the salience network. We therefore propose that the mediation
      of AVH in the context of schizophrenia spectrum disorders involves the
      attribution of an excess of negative salience by anterior-cingulate areas to
      linguistic input from Broca's right homologue, followed by subsequent processing
      errors in areas further 'downstream' the causal chain of events. We provide a
      detailed account of the origin of AVH for this patient group, and make
      suggestions for selective interventions directed at the most relevant brain
      areas.

PMID- 30273842
TI  - CSF leukocyte, polykaryocyte, protein and glucose: Their cut-offs of judging
      whether post-neurosurgical bacterial meningitis has been cured.
AB  - OBJECT: This paper is aimed to explore a reasonable guideline for distinguishing
      whether post-neurosurgical bacterial meningitis has completely been cured, so as
      to avoid the deficient or excessive treatment for post-neurosurgical bacterial
      meningitis. PATIENTS AND METHODS: We conducted a retrospective analysis of 46
      patients who attended General Hospital of Chinese People's Armed Police Force in
      Beijing, China, from January 1, 2014 to April 30, 2016. The CSF leukocyte,
      polykaryocyte, protein and glucose had been tested when their antibiotic
      treatments were empirically stopped. Between the non-relapse and relapse groups,
      Wilcoxon Rank Sum test was used to compare the differences of CSF leukocyte and
      polykaryocyte, and t-test was applied to contrast the distinctions of CSF protein
      and glucose, then, the thresholds of significant items were estimated by ROC
      curve. RESULTS: The CSF leukocyte counts in non-relapse group are 23.72 +/-
      14.12/mm3, which are statistically less than the relapse group's (47.00 +/-
      1.00/mm3, P = 0.014), so does the CSF polykaryocyte counts (1.74 +/- 4.84/mm3
      &4.67 +/- 1.15/mm3, P = 0.012). Between the two groups, the AUCs of leucocyte and
      polykaryocyte are 0.926 (95% CI = 0.845-1.0, P = 0.014) and 0.884 (95%CI = 0.786
      0.982, P = 0.028), respectively. Their critical values are 44/mm3 (sensitivity =
      1, specificity = 0.907) and 3/mm3 (sensitivity = 1, specificity = 0.837).
      Conversely, CSF protein and glucose have no statistic differences between the two
      groups. CONCLUSION: Both CSF leukocyte and polykaryocyte can satisfactorily
      indicate whether the post-neurosurgical bacterial meningitis has completely been
      cured, 0-44/mm3 is recommended as the reference range of CSF leukocyte, and the
      CSF polykaryocyte' s is 0-3/mm3.

PMID- 30273843
TI  - Low glucagon-like peptide-1 (GLP-1) concentration in serum is indicative of mild
      cognitive impairment in type 2 diabetes patients.
AB  - OBJECTIVES: To reveal potential association between glucagon-like peptide 1 (GLP
      1) concentration in serum and mild cognitive function impairment (MCI) in type 2
      diabetes mellitus (T2DM) patients. PATIENTS AND METHODS: A total of 106 T2DM
      patients and 47 normal controls were recruited in this study. Montreal Cognitive
      Assessment (MoCA) was performed in all subjects. Among the 106 patients, 52
      presented with MCI. Fasting blood glucose (FBG), total cholesterol (TC), low
      density cholesterol (LDL-C), high-density cholesterol (HDL-C), triglyceride (TG),
      uric acid (UA) and GLP-1 levels were also assessed in all subjects. RESULTS:
      Patients with MCI had higher serum concentrations of FBG and TC and lower
      concentrations of GLP-1 and HDL-C than controls. Bivariate correlation analysis
      showed that MCI in T2DM patients closely correlated with FBG, HDL-C, and GLP-1
      levels. Moreover, ordinal regression analysis showed that GLP-1 concentration in
      serum was protective for MCI in T2DM patients (OR = 0.025; 95%CI: 0.005-3.934).
      CONCLUSIONS: Our results indicated that low concentration of GLP-1 may play a
      role in the pathogenesis of MCI in T2DM patients.

PMID- 30273844
TI  - LCD: A Fast Contrastive Divergence Based Algorithm for Restricted Boltzmann
      Machine.
AB  - Restricted Boltzmann Machine (RBM) is the building block of Deep Belief Nets and
      other deep learning tools. Fast learning and prediction are both essential for
      practical usage of RBM-based machine learning techniques. This paper proposes
      Lean Contrastive Divergence (LCD), a modified Contrastive Divergence (CD)
      algorithm, to accelerate RBM learning and prediction without changing the
      results. LCD avoids most of the required computations with two optimization
      techniques. The first is called bounds-based filtering, which, through triangle
      inequality, replaces expensive calculations of many vector dot products with fast
      bounds calculations. The second is delta product, which effectively detects and
      avoids many repeated calculations in the core operation of RBM, Gibbs Sampling.
      The optimizations are applicable to both the standard contrastive divergence
      learning algorithm and its variations. In addition, this paper presents how to
      implement these optimizations effectively on massively parallel processors.
      Results show that the optimizations can produce several-fold (up to 3X for
      training and 5.3X for prediction) speedups.

PMID- 30273845
TI  - Development of a system dynamics model for polycyclic aromatic hydrocarbons and
      its application to assess the benefits of pollution reduction.
AB  - A dynamic multimedia transport (DMT) model for polycyclic aromatic hydrocarbons
      (PAHs) was constructed using the system dynamics software STELLA to simulate the
      transmission and flow of PAHs in different media. Humans are primarily exposed to
      PAHs via ingestion. Thus, this study used the DMT model to simulate the
      concentrations of PAHs in food media and the human body and assess the risk of
      harm to humans. On the basis of the hypothesis of PAH reduction in the Taiwanese
      steel industry, two scenarios were used (cases I and II), and integration
      indicators such as the Air Resource Co-Benefit Model of air pollutants,
      greenhouse gases, and PAHs reduction was established for the cost-benefit
      analysis of the reduction scenarios. This study not only established Taiwan's
      PAHs dynamic multimedia transmission model successfully but also performed a
      reduction scenario on the steel industry. In the year 2025, the total costs for
      cases I and II will be USD 690 and USD 694 million per year, respectively, and
      the total benefits will be USD 492 and 1669 million per year, respectively.
      Therefore, case II is preferable to case I in terms of benefit ratio (2.40 vs.
      2.35, respectively).

PMID- 30273846
TI  - Ecotoxicological effects of fertilizers made from pulping waste liquor on
      earthworm Eisenia fetida.
AB  - In recent years, increasing efforts have focused on production of organic
      inorganic compound fertilizers using ammonium sulfite pulping waste liquor.
      However, their ecological effects on soil have not been studied. In this study,
      earthworm Eisenia fetida was exposed to various doses (0, 0.13, 0.26 and 0.52
      kg/m2) for different time (7, 14, 21, and 28 d) to evaluate the effects of
      fertilizers made from pulping waste liquor, including reactive oxygen species
      (ROS) generation, antioxidant enzymes activities, glutathione S-transferase
      enzyme (GST) activity, malondialdehyde (MDA) content and DNA damage. Results
      showed that there were significant increase of ROS and MDA levels after 14 d,
      inducing production of antioxidant enzymes (superoxide dismutase (SOD),
      peroxidase (POD) and catalase (CAT)) as well as GST. Before 14 d, excess ROS and
      MDA caused damage to the DNA of earthworms, leading to gradual increase of Olive
      tail moment (OTM) in the comet assay. With the exposure time extended to 28 d,
      owing to the combined effects of elimination of free radicals by antioxidant
      enzymes and detoxification enzymes as well as self-repairing function of cells,
      ROS and MDA levels declined slightly and OTM gradually decreased. In summary,
      this study indicated that there was a toxicological effect on earthworms when
      fertilizers made from pulping waste liquor were applied to soil, which needs more
      attention.

PMID- 30273847
TI  - Endocrine disruption, oxidative stress and lipometabolic disturbance of Bufo
      gargarizans embryos exposed to hexavalent chromium.
AB  - The aim of the current study was to determine the potential developmental and
      metabolic abnormalities caused by Cr (VI) exposure on Bufo gargarizans (B.
      gargarizans) embryos. B. gargarizans embryos were treated with different
      concentrations of Cr (VI) (13, 52, 104, 208, and 416 MUg Cr6+ L-1) for 6 days.
      Morphological abnormalities, total length, weight and developmental stage were
      monitored. Malformations of embryos were also examined using scanning electron
      microscopy (SEM). In addition, the transcript levels of several genes associated
      with lipid metabolism, oxidative stress, and thyroid hormones signaling pathways
      were also determined. Our results showed a time-dependent inhibitory effect of Cr
      (VI) on the growth and development of B. gargarizans embryos. On day 4, total
      length, weight, and developmental stage were significantly lower at 416 MUg Cr6+
      L-1 relative to control embryos. On day 6, significant reductions in total
      length, weight, and developmental stage were observed at 104, 208, and 416 MUg
      Cr6+ L-1. Malformed embryos were found in all Cr (VI) treatments, which were
      characterized by axial flexures, yolk sac edema and rupture, surface tissue
      hyperplasia, stunted growth, wavy fin and fin flexure. RT-qPCR results showed
      that exposure to Cr (VI) down-regulated TRbeta and Dio2 mRNA expression and up
      regulated Dio3 mRNA level at 416 MUg Cr6+ L-1. The transcript levels of SOD and
      GPx were upregulated at 52, 208, and 416 MUg Cr6+ L-1, while the transcript level
      of HSP90 was downregulated at 52, 208, and 416 MUg Cr6+ L-1. Also, mRNA
      expression of lipid synthesis-related genes (FAE and ACC) were significantly
      downregulated in embryos treated with 208 and 416 MUg Cr6+ L-1, but mRNA
      expression of fatty acid beta-oxidation-related genes (ACOX, CPT, and SCP) was
      significantly upregulated at 416 MUg Cr6+ L-1. Therefore, our results suggested
      that Cr (VI) could disrupt thyroid endocrine pathways and lipid synthesis,
      leading to the inhibition of growth and development in B. gargarizans embryos.
      Furthermore, the decreased ability of scavenging ROS induced by Cr (VI) might be
      responsible for the teratogenic effects of Cr (VI).

PMID- 30273848
TI  - Quantitative screening level assessment of human risk from PCBs released in
      glacial meltwater: Silvretta Glacier, Swiss Alps.
AB  - Persistent organic pollutants (POPs) are entrained within glaciers globally,
      reemerging in many alpine ecosystems. Despite available data on POP flux from
      glaciers, a study of human health risk caused by POPs released in glacial
      meltwater has never been attempted. Glaciers in the European Alps house the
      largest known quantity of POPs in the Northern Hemisphere, presenting an
      opportunity for identification of potential risk in an endmember scenario case
      study. With methodology developed by the US Environmental Protection Agency
      (EPA), we provide a regional screening level human risk analysis of one class of
      POPs, polychlorinated-biphenyls (PCB) that have been measured in melt waters from
      the Silvretta Glacier in the Swiss Alps. Our model suggests the potential for
      both cancer and non-cancer impacts in residents with lifetime exposure to current
      levels of PCB in glacial meltwater and average consumption of local fish. For
      residents with an abbreviated 30-year exposure timeframe, the risk for cancer and
      non-cancer impacts is low. Populations that consume higher quantities of local
      fish are predicted to be at a greater risk, with risk to lifetime consumers
      higher by an order of magnitude. Based on the results of our screening study, we
      suggest that local government move to the next step within the risk assessment
      framework: local monitoring and management. Within the Alps, other glacial
      watersheds of a similar size and latitude may see comparable risk and our model
      framework can be adapted for further implementation therein.

PMID- 30273849
TI  - Bacterial community shaped by heavy metals and contributing to health risks in
      cornfields.
AB  - Scientists are increasingly aware that heavy metal contamination in soils,
      especially in farmland ecosystems, can negatively affect human health and alter
      the bacterial community that plays a critical role in plant growth and heavy
      metal accumulation. The goal of the present paper was to uncover how various
      heavy metals and non-metallic elements affect human health and bacterial
      diversity in cornfields and to explore the contribution of soil bacteria to heavy
      metal accumulation in crops. Soil samples were collected from five counties in
      Shandong Province, China, where abnormally high levels of heavy metals and
      metalloids were caused by mining and heavy industry. We calculated a hazard
      quotient (HQ) to evaluate the health risk these heavy metals cause and analyzed
      the soil bacterial community using 16S rRNA gene sequencing. The HQ results
      showed that As posed the greatest threat to human health followed by Pb although
      concentrations of all metals did not reach the health risk threshold. Meanwhile,
      principal component analysis (PCA) and redundancy analysis (RDA) revealed soil
      bacterial richness was significantly influenced by As, Ni, and Cr as well as pH
      and phosphorus, but not by the species diversity of aboveground weeds. The most
      abundant bacteria in our study region were heavy metal tolerant groups,
      specifically Actinobacteria and Proteobacteria. Moreover, correlation analysis
      suggested that Actinobacteria might reduce the phytoaccumulation of Cr, Cu, Zn,
      and Hg in corn, while Proteobacteria might weaken phytoaccumulation of Pb, Ni,
      As, and Cd. Our results verified that heavy metals play an important role in
      shaping the soil bacterial community. Using native bacteria in farmland provides
      a potential biological strategy for reducing the health risk posed by heavy
      metals related to food consumption.

PMID- 30273850
TI  - Measurement and prediction of bioconcentration factors of organophosphate flame
      retardants in common carp (Cyprinus carpio).
AB  - The increase in the production and usage plus the toxicity nature of
      organophosphate flame retardants (OPFRs) has become a concern. However, limited
      information is available about the bioaccumulation potential of OPFRs in fish. In
      this study, we determined the 96 h LC50 s, and evaluated the bioaccumulation
      potential of six most frequently reported OPFRs in gill, kidney, liver, and
      muscle tissues of common carp (Cyprinus carpio) for 48 d, and a quantitative
      structure-activity relationship (QSAR) model was developed to predict
      bioconcentration factors (BCFs) for the remaining 16 OPFRs. The BCFs and half
      lives (t1/2) in the tissues ranged from 6.54 (Tris (2-chloroisopropyl) phosphate,
      (TCPP)) to 528.15 (Tris (2-ethylhexyl) phosphate (TEHP)), and 2.25-5.78 days,
      respectively. The tissue-specific concentration and BCFs values followed the
      order of liver > kidney >= intestine >> muscle. The proposed QSAR model with a
      high cross-validated value (Q2(cum)) of 0.930 and a correlation coefficient of
      0.94 was obtained and was able to predict log BCF from parameters related to
      molar volume and isotropic average static field polarizability. The results show
      that the model has a high level of accuracy, making the proposed approach a
      suitable method for predicting the log BCF.

PMID- 30273851
TI  - Porous MnFe2O4@SiO2 magnetic glycopolymer: A multivalent nanostructure for
      efficient removal of bacteria from aqueous solution.
AB  - The focuses of this research is to prepare an efficient magnetic glycopolymer for
      bacteria removal from aqueous solution. To perform this idea; porous MnFe2O4@SiO2
      was functionalized with glucose and or maltose as an anchors to adhere onto
      bacteria cell surface. Aminopropyltriethoxysilane was employed to link the
      saccharides on magnetic nanoparticle surface. The hybrid materials were
      characterized with XRD, VSM, FT-IR, FESEM, TEM, zeta potential measurement and
      elemental mapping. Microscopic image showed that MnFe2O4 is in cluster form
      composed from tiny nanoparticles. After saccharide functionalization hybrid
      composite generate hyper-crosslinked porous structure as a result of polysilicate
      formation due to hydrolysis of silica source. Escherichia coli and bacillus
      subtilis were selected as sample pathogens to evaluate the bacteria capturing
      ability of the magnetic glycopolymer. At the optimum conditions (pH = 6, time of
      20 min, dosage of 15 mg) removal efficiency was more than 99% using both
      saccharide.

PMID- 30273852
TI  - Removal of hexavalent chromium ions by core-shell sand/Mg-layer double hydroxides
      (LDHs) in constructed rapid infiltration system.
AB  - This study aimed to determine the efficiencies and mechanisms of hexavalent
      chromium (Cr(VI)) removal with modified sand coated by Mg-LDHs in constructed
      rapid infiltration system (CRIS). Mg-LDHs (MgAl-LDHs, MgFe-LDHs) were prepared by
      co-precipitation method and in situ coated onto the surface of original sand.
      Scanning Electron Microscope (SEM) and X-Ray Fluorescence Spectrometer (XRFS)
      were used to analyze physicochemical properties of sand/Mg-LDHs composites.
      Results obtained confirmed the successful LDHs-coating modification. During the
      purification experiments, the average removal rates of Cr(VI) were 47.62% for
      sand/MgAl-LDHs, 34.15% for sand/MgFe-LDHs and 11.61% for original sand,
      respectively. The sand/Mg-LDHs had a higher Langmuir adsorption capacity and
      desorption capability for Cr(VI) compared to original sand. The adsorption
      kinetic data of different adsorbents were better described by pseudo-second-order
      model. Intra-particle diffusion model was also used to elucidate the adsorption
      mechanism. Moreover, extracellular polymeric substances, biomass and enzymatic
      activity of microbes on the modified and original sand were testified and
      analyzed to study microbial effect on Cr(VI) removal in test columns. Through a
      rough economic estimation, the reagent cost of sand/MgAl-LDHs synthesis was only
      RMB Y 0.24/Kg. It could be concluded that MgAl-LDHs modified sand is an efficient
      and economical substrate of CRIS for Cr(VI) removal.

PMID- 30273854
TI  - Transcriptomic response of Arabidopsis thaliana roots to naproxen and
      praziquantel.
AB  - Exposition to pharmaceutical compounds released to the environment is considered
      as a potential risk for various organisms. We exposed Arabidopsis thaliana plants
      to naproxen (NAP) and praziquantel (PZQ) in 5 uM concentration for 2 days and
      recorded transcriptomic response in their roots with the aim to estimate
      ecotoxicity and to identify gene candidates potentially involved in metabolism of
      both compounds. Nonsteroidal anti-inflammatory drug NAP up-regulated 105 and down
      regulated 29 genes (p-value <= 0.1, fold change >= 2), while anthelmintic PZQ up
      regulated 389 and down-regulated 353 genes with more rigorous p-value <= 0.001
      (fold change >= 2). High number of up-regulated genes coding for heat shock
      proteins and other genes involved in response to biotic and abiotic stresses as
      well as down-regulation of genes involved in processes such as cell
      proliferation, transcription and water transport indicates serious negative
      effect of PZQ. NAP up-regulated mostly genes involved in various biological
      processes and signal transduction and down-regulated mainly genes involved in
      signal transduction and electron transport or energy pathways. Further, two
      cytochrome P450s (demethylation) and one methyltransferase (methylation of
      carboxyl group) were identified as candidates for phase I and several glutathione
      and glycosyltransferases (conjugation) for phase II of NAP metabolism.
      Cytochrome P450s, glutathione and glycosyltransferases seem to play role also in
      metabolism of PZQ. Up-regulation of several ABC and MATE transporters by NAP and
      PZQ indicated their role in transport of both compounds.

PMID- 30273853
TI  - Current approaches for safer design of engineered nanomaterials.
AB  - The surge of applications for engineered nanomaterials (ENMs) across multiple
      industries raises safety concerns regarding human health and environmental
      impacts. ENMs can be hazardous through various mechanisms, including, particle
      dissolution and shedding of toxic metal ions, surface reactivity and perturbation
      of cellular membranes, lysosomal membrane damage, activation of inflammation
      pathways (e.g., NLRP3 inflammasome), etc. The aim of this review is therefore to
      discuss practical approaches for the safer design of ENMs through modification of
      their physicochemical properties that can lead to acute and/or chronic toxicity.
      This is premised on our understanding of how different ENMs induce toxicity
      within various biological systems. We will summarize studies that have
      investigated nanomaterial toxicity both in vitro and in vivo to understand the
      underlying mechanisms by which nanoparticles can cause inflammation, fibrosis,
      and cell death. With this knowledge, researchers have identified several design
      strategies to counter these mechanisms of toxicity. In particular, we will
      discuss how metal doping, surface coating and covalent functionalization, and
      adjustment of surface oxidation state and aspect ratio of ENMs could reduce their
      potential adverse effects. While these strategies might be effective under
      certain experimental and exposure scenarios, more research is required to fully
      apply this knowledge in real life applications of nanomaterials.

PMID- 30273855
TI  - Effect of external resistance on the sensitivity of microbial fuel cell biosensor
      for detection of different types of pollutants.
AB  - The relatively poor sensitivity is the main bottleneck restricting the
      application of microbial fuel cell biosensor (MFC-biosensor) for toxicity
      monitoring. Previous studies have shown that external resistance (Rext) had an
      obvious effect on sensor sensitivity. However, these studies reported different
      results and the reason of this discrepancy was not clear. The objective of this
      research was to observe the effect of Rext on sensor sensitivity when detecting
      different types of pollutants and reveal its microbiological mechanism. Results
      demonstrated that the optimal Rext of MFC-biosensor varied with the type of
      pollutants. The optimal values for detecting avermectins, tetracyclines and heavy
      metals were 100 Omega, 330 Omega and 680 Omega, respectively. This discrepancy
      was mainly due to the visible differences in anodic microbial communities at
      different Rext settings. Both Azospirillum and Acinetobacter were susceptible to
      Cd and Pb, occuping 19.20% of the anodic microbial population in 680 Omega MFC
      biosensor. Pseudomonas accounted for 10.73% in 330 Omega MFC-biosensor and
      possessed the sensitivity to tetracyclines. As for 100 Omega MFC-biosensor, the
      avermectin-intolerant Ocillibacter made up 2.55% of the anodic microbial
      community. This study indicated that the Rext of MFC-biosensor should be
      optimized according to the potential pollutants.

PMID- 30273856
TI  - Anxiety attacks with or without life-threatening situations, major depressive
      disorder, and suicide attempt: a nationwide community sample of Korean adults.
AB  - Regardless of categorical diagnosis, many psychiatric patients suffer from sudden
      attack of fear or intense anxiety. In this study, we defined anxiety attacks to
      refer to these phenomena and investigated their association with depression and
      suicide attempts. A total of 12,532 adults randomly selected population through
      the one-person-per-household method completed a face-to-face interview using the
      Korean version of Composite International Diagnostic Interview (K-CIDI). A total
      of 5.88% reported to have experienced anxiety attacks. Among them, 46.5% reported
      to have experienced anxiety attacks without life-threatening situations. 'Anxiety
      attacks' group reported more suicidal ideation, plan, and attempts, which were
      even higher frequencies in 'anxiety attacks without life-threatening situations'
      group than 'anxiety attacks only with life-threatening situations' group and
      showed stronger association with lifetime suicide attempts when it had comorbid
      major depressive disorder (MDD) (AOR = 9.69, 95%CI 5.90-15.90), compared with
      'never' group. There was no association between each symptom of patients with
      anxiety attacks and their lifetime suicide attempt. In conclusion, the finding
      suggests that there are as many individuals who experience anxiety attacks
      without life-threatening situations as those with life-threatening situations.
      And anxiety attacks appear to be relevant to an increased risk of suicide
      attempt, especially without life-threatening situations and with comorbid MDD.

PMID- 30273857
TI  - Prevalence of depression among type 2 diabetes mellitus patients in India: A meta
      analysis.
AB  - Depression as a co-morbid condition in type 2 diabetes mellitus (T2DM) patients
      is associated with significant morbidity, mortality, and rising health economic
      burden. Indian healthcare system is heavily burdened with T2DM, and it is
      important to understand the prevalence of depression associated with T2DM. This
      meta-analysis conducted as per the registered protocol (PROSPERO registration:
      CRD42016051552), searched for published studies in the databases including
      MEDLINE and Embase till 31st August 2018. The modified Newcastle-Ottawa Scale was
      used to assess the methodological quality. The pooled prevalence of depression
      among T2DM patients was estimated as primary outcomes, while prevalence based on
      demographic sub-group was estimated as the secondary outcome. In total, 43
      studies including 10,270 patients fulfilled the eligibility criteria and were
      included in the analysis. The pooled prevalence of depression in T2DM patients
      was found to be 38% (95% CI: 31%-45%). Presence of depression in people with type
      2 diabetes was more often associated with the presence of complications with an
      odds ratio of 2.33, 95% CI: 1.62-3.36, p < 0.00001. Overall, the study found a
      high prevalence of depression among T2DM patients in India. Diabetes management
      programs in India may consider early screening of depression in T2DM patients.

PMID- 30273858
TI  - Arsenic surface complexation behavior in aqueous systems onto Al substituted Ni,
      Co, Mn, and Cu based ferrite nano adsorbents.
AB  - The present study is about surface complexation behavior of arsenic species
      adsorbed onto ternary metal oxide adsorbents (Ni-Al-Fe, Co-Al-Fe, Mn-Al-Fe, and
      Cu-Al-Fe). The analysis is carried out by X-ray absorption spectroscopy (XAS)
      tool. XANES (MU(E) vs. E) spectra close to the absorption edge (i.e., As K-edge)
      of all samples are observed along with the As(III) and As(V) standards. The first
      derivative of XANES for Ni-As(V), and Cu-As(V) samples agree with that of As(V)
      standards, respectively. Whereas, As(III) adsorbed adsorbent systems (i.e., Ni,
      Co, Mn, and Cu) are observed with mixed oxidation state of arsenic. A total of 65
      85 % is observed with initial oxidation state (As(III) or As(V)), and remaining
      15-35 % is observed with modified oxidation state (As(V) or As(III)) that
      explains the occurrence of possible charge transfer. EXAFS analysis shows the As
      O bond distances in the range of 1.7-1.8 A. The corresponding As-M bond distances
      are around 2.7, 3.2, and 3.6 A which confirms the formation various edge sharing
      (2E), and corner sharing (2C, 1V) surface complexes. Surface coverage is
      understood as an important parameter as bidentate attachments (2E, 2C) are
      evident in As(III), and As(V), but monodentate attachments (1V) are only observed
      in As(V).

PMID- 30273859
TI  - Successful Secondary Engraftment of Pancreatic Ductal Adenocarcinoma and
      Cholangiocarcinoma Patient-Derived Xenografts After Previous Failed Primary
      Engraftment.
AB  - BACKGROUND: Patient-derived xenografts (PDX) provide histologically accurate
      cancer models that recapitulate patient malignant phenotype and allow for highly
      correlative oncologic in-vivo downstream translational studies. Primary PDX
      engraftment failure has significant negative consequences on programmatic
      efficiency and resource utilization and is due to either no tumor growth or
      development of lymphoproliferative tumors. We aimed to determine if secondary
      engraftment of previously cryopreserved patient tumor tissues would allow salvage
      of PDX models that failed previous primary engraftment and increase overall
      engraftment efficiency. METHODS: Patient hepatobiliary and pancreatic cancers
      that failed primary engraftment were identified. Previously cryopreserved primary
      patient cancerous tissues were implanted into immunodeficient mice (NOD/SCID).
      Mice were monitored, growth metrics calculated, and secondary engraftment
      outcomes were recorded. Established PDX were verified and compared to original
      patient tissue through multiple generations by a GI pathologist. RESULTS: We
      identified 55 patient tumors that previously failed primary engraftment: no tumor
      growth (n = 46, 84%) or lymphoproliferative tumor (LT) (n = 9, 16%). After
      secondary implantation using cryopreserved patient tissues, 29 new histologically
      validated PDX models were generated with an overall secondary engraftment rate of
      53% for all tumor types with greatest yield in pancreatic and biliary tract
      cancers. Of the secondary engraftment failures (n = 26), 21 (38%) were due to no
      growth and 5 (9%) developed LT. CONCLUSION: Secondary PDX engraftment using
      cryopreserved primary cancerous is feasible after previous failed engraftment
      attempts and can result in a 50% increase in overall engraftment efficiency with
      decreases in LT formation. This technique allows for salvage of critical patient
      PDX models that would otherwise not exist. SYNOPSIS: Patient-derived xenografts
      have many important translational applications however can be limited by
      engraftment failure. We demonstrate optimized methodology utilizing
      cryopreservation of primary tumor tissue that allows for subsequent successful
      secondary engraftment and creation of PDX models that failed previous primary
      engraftment and allowed salvage of patient PDX models that would otherwise not
      exist.

PMID- 30273861
TI  - Uptake and translocation of 14C-Carbamazepine in soil-plant systems.
AB  - Carbamazepine (CBZ) is an antiepileptic drug that is frequently detected in
      wastewater treatment plants, soil and plants after irrigation with treated
      wastewater or application of biosolids. However, little information is available
      on the fate and uptake of CBZ in edible vegetables. In this study,
      radioautographic visualization of the 14C distribution revealed that 14C-CBZ can
      be taken up by all three ready-to-eat vegetables. Furthermore, a mass-balance
      study was conducted to evaluate the dynamic processes of the uptake and
      translocation of CBZ by 14C labeling. 14C-CBZ was gradually taken up with the
      growth of vegetables, with maximum uptake ratios of 2.19 +/- 0.15, 2.86 +/- 0.24
      and 0.25 +/- 0.05% of applied 14C in celery, carrot and pak choi, respectively.
      The bioconcentration factors (BCFs) based on 14C measurements ranged from 7.6 to
      26.1 for celery, 3.6-12.9 for carrot, and 4.4-44 for pak choi. 14C-CBZ was easily
      translocated from the roots to the leaves and/or stems. The amendment of
      biosolids had a significant inhibitory effect on the uptake and translocation of
      14C-CBZ from soil.

PMID- 30273860
TI  - Markers of Mitochondrial Metabolism in Tumor Hypoxia, Systemic Inflammation, and
      Adverse Outcome of Rectal Cancer.
AB  - Tumor hypoxia contributes to therapy resistance and metastatic progression of
      locally advanced rectal cancer (LARC). We postulated that the tumor mitochondrial
      metabolism, manifested by reactive oxygen species (ROS) and mitochondrial DNA
      (mtDNA) damage, reflects how hypoxic conditions connect to cancer-induced
      systemic inflammation and poor outcome. Levels of ROS and mtDNA damage were
      analyzed in three colorectal cancer (CRC) cell lines cultured for 24 hours under
      normoxia (21% O2) or hypoxia (0.2% O2) and serum sampled at the time of diagnosis
      from 35 LARC patients participating in a prospective therapy study. Compared with
      normoxia, ROS were significantly repressed and mtDNA damage was significantly
      enhanced in the hypoxic CRC cell lines; hence, a low ratio of ROS to mtDNA damage
      was an indicator of hypoxic conditions. In the LARC patients, low serum ROS were
      associated with elevated levels of circulating carcinoembryonic antigen and tumor
      choline concentration, both indicative of unfavorable biology, as well as adverse
      progression-free and overall survival. A low ratio of ROS to mtDNA damage in
      serum was associated with poor local tumor response to the neoadjuvant treatment
      and, of note, elevated systemic inflammation factors (C-reactive protein, the
      interleukin-1 receptor antagonist, and factors involved in tumor necrosis factor
      signaling), indicating that deficient treatment response locally and detrimental
      inflammation systemically link to a hypoxic mitochondrial metabolism. In
      conclusion, serum ROS and damaged mtDNA may be markers of the mitochondrial
      metabolism driven by the state of oxygenation of the primary tumor and possibly
      implicated in systemic inflammation and adverse outcome of LARC.

PMID- 30273862
TI  - Determination of the vertical profile of aerosol chemical species in the
      microscale urban environment.
AB  - This study developed a lightweight air composition measuring equipment (ACME)
      mounted in unmanned aerial vehicles (UAVs) to measure the vertical distribution
      characteristics of PM2.5 chemical species in the micro-scale urban environment
      for the first time. 212 samples collected from 0 to 350 m above ground level were
      analyzed for water-soluble ions. The concentrations of most ions on the above
      ground level were higher than that on the ground surface during the sampling
      period. The measurements of the total ion concentrations were approximately 54 to
      26% of the PM2.5 mass concentrations on the ground surface. The concentrations of
      NH4+ and NO3- decreased with increases in the height from the ground, which may
      be related to the influence of the vehicle emissions and human activities. NO2-
      and SO42- both had a peak concentration on the higher vertical altitude at night
      in the sea-land wind system. In the southern wind system, the emissions of sea
      salts, dust, and stationary pollution, might be transported by the regional
      prevailing airflow from the southern coastal area, were the major pollutant
      sources above the boundary layer. The vertical distribution of ionic
      concentrations and wind field provided information concerning changes in
      pollutant transport and source regions that affect the local air quality. The
      ACME mounted in UAVs is the feasible and convenient method to fast understand the
      vertical distributions of aerosol chemical species. It provides important
      information about the accumulation and diffusion effects by the boundary layer
      variation to aerosol characteristics, which is difficulty observed from the
      conventional ground-based measurements. In future, this technology is the useful
      application for investigating the pollutant species emitted from the smokestack
      and the sudden pollution accident.

PMID- 30273863
TI  - Synergistic effects of phosphorus and humic acid on the transport of anatase
      titanium dioxide nanoparticles in water-saturated porous media.
AB  - The (un)intentional release of titanium dioxide nanoparticles (TiO2 NPs) poses
      potential risks to the environment and human health. Phosphorus (P) and humic
      acid (HA) usually coexist in the natural environments. This study aims at
      investigating the transport and retention behaviors of TiO2 NPs in the single and
      binary systems of P and HA in water-saturated porous media. The experimental
      results showed that HA alone favored the transport of TiO2 NPs in sand columns to
      a greater extent than that of P alone at pH 6.0. Interestingly, the co-presence
      of P and HA acting in a synergistic fashion enhanced the transport of TiO2 NPs in
      sand-packed columns more significantly compared to that in the single-presence of
      P or HA. Particularly, P plays a dominant role in the synergistic effect. This is
      largely due to the competitive effect between P and HA for the same adsorption
      sites on the sand surfaces favorable for TiO2 NPs retention. A two-site kinetic
      attachment model that considers Langmuirian blocking of particles at one site
      provided a good approximation of TiO2 NPs transport. Modeled first-order
      attachment coefficient (k2) and the maximum solid-phase retention capacity on
      site 2 (Smax2) for P or HA alone were larger than those in the co-presence of P
      and HA, suggesting a less retention degree of TiO2 NPs in the binary system of P
      and HA. Our findings indicate that the mobility of TiO2 NPs is expected to be
      appreciable in soil and water environments, where P and HA are rich and always co
      present at low pH conditions.

PMID- 30273864
TI  - Chemical and biological transfer: Which one is responsible for the maternal
      transfer toxicity of tris(1,3-dichloro-2-propyl) phosphate in zebrafish?
AB  - Maternal transfer toxicity of chemicals has mainly focused in fish on the
      chemical transfer from maternal generation to offspring, and limited information
      is available for the evaluation of effects of chemicals from a biological
      transfer perspective. In this study, first-generation (F0) zebrafish larvae (D.
      rerio) were exposed to 0, 50, 500 or 5000 ng/L TDCIPP from 14 days post
      fertilization (dpf) to 120 dpf. F0-generation zebrafish were paired, and F1
      generation embryos were collected and continuously exposed to the same
      concentrations of TDCIPP until 150 dpf. F1-generation females were then paired
      with unexposed adult males, and maternal transfer effects on survival rate and
      body length were evaluated. Results demonstrated that maternal exposure to TDCIPP
      for two generations significantly decreased body length of F2-generation larvae,
      suggesting the occurrence of maternal transfer toxicity. The transfer of TDCIPP
      from maternal generation to offspring was evident, but microinjection of equal
      amounts of TDCIPP did not affect survival and body length of zebrafish larvae.
      Furthermore, maternal exposure to TDCIPP changed the concentrations of partial
      mRNAs and proteins in their eggs, and those changes were linked to maternal
      transfer toxicity (e.g., growth inhibition). These results suggested that in
      zebrafish changes in biological transfer may explain, at least in part, the
      observed maternal transfer toxicity of TDCIPP.

PMID- 30273865
TI  - Long-term impact of cement plant emissions on the elemental composition of both
      soils and pine stands and on the formation of Scots pine seeds.
AB  - We investigated the long-term impact of the largest Russian cement plant on
      mesopodzol sandy soils and Scots pine stands. We determined the distributions of
      the total and available pools of Ca, Mg, K, Na, Mn, Fe, Zn, Ni, Cu, Pb and Cd in
      the soil profile to a depth of 60 cm (illuvial horizon) as well as the
      accumulation patterns of these elements in the vegetative and generative organs
      of Scots pine trees. High Ca accumulation in the impact zone soils was a result
      of CaO emissions by a cement plant. Also, CaO became the main cause of soil
      profile alkalization due to neutralization of soil acids and formation of calcium
      hydroxide or carbonates. Alkalization immobilized substantial amounts of Fe, Mn,
      Zn and Ni in the soil, reducing their availability. The most prominent effect of
      long-term cement production was a prominent Mn deficiency in vegetative and
      generative Scots pine organs due to the exhaustion of the available Mn pool in
      the illuvial horizon. The miniaturization of cones, a decrease in seed yield and
      a reduction in seed germinability were observed in the emission impact zones.
      Pretreatment of Mn-deficient seeds with manganese eliminated Mn deficiency but
      did not increase seed germination.

PMID- 30273866
TI  - The interaction between particulate organic matter and copper, zinc in paddy
      soil.
AB  - Particulate organic matter (POM) acts as a metals sink in soil, but only a few
      studies focused on the interaction of POM and heavy metals in paddy soil. The aim
      of this study is to investigate the interaction between POM and Copper (Cu)/Zinc
      (Zn). Two levels of Cu (100, 400 mg kg-1) and Zn (250, 500 mg kg-1) were used in
      a soil culture experiment. Our results showed that POM was porous structure and
      varied in size. Hydroxyl and carboxyl involved in POM adsorption of Cu and Zn.
      Rhizosphere effects roughen the surface of POM and enhanced the capacity of POM
      on heavy metals absorption. Cu-humic (26.2-33.9%) and Cu-citrate (38.5-42.4%)
      were dominated in POM, and Cu-goethite (41.7-57.7%), Cu-sulphide (6.6-27.6%) was
      dominated in soil. Rhizosphere effects decreased the proportion of organic-bond
      Cu along with the increasing the proportion of Cu-sulphide in POM. Addition of Cu
      and Zn inhibited the degradation of POM but rhizosphere effects promoted. Carbon
      content was increased in POM by heavy metal and rhizosphere effects. Our findings
      indicated that POM tended to retain the heavy metals in soil and heavy metals
      inhibited the degradation of POM, however, rhizosphere effects decreased the
      stability of POM-metals interactions.

PMID- 30273867
TI  - Greenspace seems protective of both high and low blood pressure among residents
      of an Alpine valley.
AB  - BACKGROUND: There is some data suggesting that residential greenspace may protect
      against high blood pressure in urbanized areas, but there is no evidence of
      effects on hypotension, in less urbanized areas, and in idiosyncratic geographic
      contexts such as mountain valleys. OBJECTIVES: The current study aimed to
      investigate the associations between residential greenspace and blood pressure in
      an alpine valley in Austria. METHODS: We conducted a cross-sectional survey of a
      representative sample of 555 adults living in the Lower Inn Valley, Austria.
      Several definitions of blood pressure were employed: continuously-measured
      systolic (SBP) and diastolic blood pressure (DBP), doctor-diagnosed hyper- and
      hypotension, and high- and low blood pressure medication use. Greenspace metrics
      considered were: Normalized Difference Vegetation Index (NDVI), Soil Adjusted
      Vegetation Index (SAVI), and tree cover as measures of surrounding greenness in
      circular buffers of 100 m, 300 m, 500 m, and 1000 m around the home; distance to
      different types of structured green space; and having a domestic garden and a
      balcony. Relationships were examined across different definitions of blood
      pressure and greenspace and evaluated for potential effect modification by
      demographic factors, presence of a domestic garden/balcony, adiposity, and
      traffic sensitivity. RESULTS: Higher overall greenness was associated with 30-40%
      lower odds of hyper/hypotension and 2-3 mm Hg lower SBP. Similar pattern was
      revealed for tree cover, however, associations with hypertension were less
      consistent across buffers, and SBP and DBP were lower only in association with
      greenness in the 100-m buffer. Having a domestic garden also seemed protective of
      high DBP. Residing near to forests, agricultural land, or urban green spaces was
      not related to blood pressure. Higher NDVI500-m was stronger associated with
      lower SBP in those having a domestic garden, while the effect on DBP was stronger
      in overweight/obese participants. CONCLUSION: These findings support the idea
      that greenspace should be considered as protective of both high and low blood
      pressure, however, underlying mechanisms remain insufficiently understood.

PMID- 30273868
TI  - The impact of social capital, land use, air pollution and noise on individual
      morbidity in Dutch neighbourhoods.
AB  - BACKGROUND: Both social and physical neighbourhood factors may affect residents'
      health, but few studies have considered the combination of several exposures in
      relation to individual health status. AIM: To assess a range of different
      potentially relevant physical and social environmental characteristics in a
      sample of small neighbourhoods in the Netherlands, to study their mutual
      correlations and to explore associations with morbidity of residents using
      routinely collected general practitioners' (GPs') data. METHODS: For 135
      neighbourhoods in 43 Dutch municipalities, we could assess area-level social
      cohesion and collective efficacy using external questionnaire data, urbanisation,
      amount of greenspace and water areas, land use diversity, air pollution
      (particulate matter (PM) with a diameter <10 MUm (PM10), PM <2.5 MUm (PM2.5) and
      nitrogen dioxide (NO2), and noise (from road traffic and from railways). Health
      data of the year 2013 from GPs were available for 4450 residents living in these
      135 neighbourhoods, that were representative for the entire country. Morbidity of
      10 relevant physical or mental health groupings was considered. Individual-level
      socio-economic information was obtained from Statistics Netherlands. Associations
      between neighbourhood exposures and individual morbidity were quantified using
      multilevel mixed effects logistic regression analyses, adjusted for sex, age
      (continuous), household income and socio-economic status (individual level) and
      municipality and neighbourhood (group level). RESULTS: Most physical exposures
      were strongly correlated with degree of urbanisation. Social cohesion and
      collective efficacy tended to be higher in less urbanised municipalities. Degree
      of urbanisation was associated with higher morbidity of all disease groupings. A
      higher social cohesion at the municipal level coincided with a lower prevalence
      of depression, migraine/severe headache and Medically Unexplained Physical
      Symptoms (MUPS). An increase in both natural and agricultural greenspace in the
      neighbourhood was weakly associated with less morbidity for all conditions. A
      high land use diversity was consistently associated with lower morbidities, in
      particular among non-occupationally active individuals. CONCLUSION: A high
      diversity in land use of neighbourhoods may be beneficial for physical and mental
      health of the inhabitants. If confirmed, this may be incorporated into urban
      planning, in particular regarding the diversity of greenspace.

PMID- 30273869
TI  - A meta-analysis of blood lead levels in India and the attributable burden of
      disease.
AB  - Multiple studies in India have found elevated blood lead levels (BLLs) in target
      populations. However the data have not yet been evaluated to understand
      population-wide exposure levels. We used arithmetic mean blood lead data
      published from 2010 to 2018 on Indian populations to calculate the average BLLs
      for multiple subgroups. We then calculated the attributable disease burden in IQ
      decrement and Disability Adjusted Life Years (DALYs). Our Pubmed search yielded
      1066 articles. Of these, 31 studies representing the BLLs of 5472 people in 9
      states met our study criteria. Evaluating these, we found a mean BLL of 6.86
      MUg/dL (95% CI: 4.38-9.35) in children and 7.52 MUg/dL (95% CI: 5.28-9.76) in non
      occupationally exposed adults. We calculated that these exposures resulted in 4.9
      million DALYs (95% CI: 3.9-5.6) in the states we evaluated. Population-wide BLLs
      in India remain elevated despite regulatory action to eliminate leaded petrol,
      the most significant historical source. The estimated attributable disease burden
      is larger than previously calculated, particularly with regard to associated
      intellectual disability outcomes in children. Larger population-wide BLL studies
      are required to inform future calculations. Policy responses need to be developed
      to mitigate the worst exposures.

PMID- 30273870
TI  - Functionalized MoS2-nanosheets for targeted drug delivery and chemo-photothermal
      therapy.
AB  - Molybdenum disulfide (MoS2) has been extensively explored for biomedical
      applications due to its excellent photothermal conversion ability. In this paper,
      we report a nanoplatform based on folic acid (FA) targeted dual-stimuli
      responsive MoS2 nanosheets and explore this for the treatment of FA-receptor
      positive human breast cancer. The nanocomposites generated had a uniform diameter
      (ca. 133 nm), and could be loaded with the anti-cancer drug doxorubicin (DOX) to
      a high capacity (151.4 mg/g). The release of DOX was greatly accelerated at pH
      5.0 as compared to pH 7.4. In addition, it was found that drug release is
      enhanced under near infrared laser (NIR) irradiation, showing that the composites
      can be used as dual responsive systems, with DOX release controllable through pH
      or NIR irradiation. MTT assays and confocal experiments showed that the MoS2
      based nanoplatform could selectively target and kill FA-positive MDA-MB-231 cells
      (a human breast cancer cell line). The platform also allowed the combination of
      chemotherapy and photothermal therapy, which led to synergistic effects superior
      to either monotherapy. The functionalized MoS2 nanoplatform developed in this
      work hence could be a potent system for targeted drug delivery and synergistic
      chemo-photothermal cancer therapy.

PMID- 30273871
TI  - Cytocompatibility assessment of Ti-Nb-Zr-Si thin film metallic glasses with
      enhanced osteoblast differentiation for biomedical applications.
AB  - Biologically safe Ti-based quaternary Ti-Nb-Zr-Si thin film metallic glass (TFMG)
      was fabricated by sputtering on Titanium alloy (Ti6Al4V or Ti alloy) substrates.
      A preliminary assessment regarding glass forming ability, thermal stability and
      corrosion behavior was performed. The amorphous nature of the film is evidenced
      from the X-ray Diffraction (XRD) and Transmission Electron Microscope (TEM) and
      Selected Area Electron Diffraction (SAED) patterns. Ion scattering spectroscopy
      (ISS) and X-ray Photoelectron Spectroscopy (XPS) were used to analyse the
      chemical composition of surface which indicated oxygen on the top surface of the
      film and confirms the presence of Ti, Nb, Si, Zr without any other impurities.
      The surface morphology of the film showed a smooth surface as observed from
      scanning electron microscope (SEM) and atomic force microscope (AFM) analysis. It
      is found that the TFMG can sustain in the body-fluid, exhibiting superior
      corrosion resistance and electrochemical stability than the bare titanium. The
      cytotoxicity studies with L929 fibroblast cells showed that coatings were graded
      as zero and non-cytotoxic in nature. No hemolysis was observed on the coated
      surface indicating a better hemocompatibility. Assay using SaOS-2 bone cells
      showed good growth on the coated surfaces. The calcium assay showed that the SaOS
      2 cells grown and differentiated on the control (Tissue Culture Polystyrene) TCPS
      surface had the highest mineral level. Higher alkaline phosphatase activity is
      obtained in SaOS-2 osteoblast cell cultures on TFMG than the control.

PMID- 30273872
TI  - Provitamin supramolecular polymer micelle with pH responsiveness to control
      release, bioavailability enhancement and potentiation of cytotoxic efficacy.
AB  - Encapsulation techniques to generate core/shell systems provide a method that
      improves physicochemical properties, which are very important in biological
      applications. beta-carotene is a common carotenoid that has shown preventive
      effects in skin diseases and vitamin A deficiency but this compound has limited
      water solubility and bioavailability, which hinder its broad application. The use
      of polyrotaxane compounds formed from cyclodextrins has allowed supramolecular
      polymer micelles (SMPMs) to be synthesized to encapsulate beta-carotene. The
      polymeric compound Pluronic F127(r) was also used to create core/shell
      nanoparticles (NPs) that contain beta-carotene. Bioactive compound encapsulation
      was fully confirmed by nuclear magnetic resonance spectroscopy and by scanning
      and transmission electron microscopy. The method based on cyclodextrin and
      lecithin allow to release slowly when the systems were exposed to an aqueous
      medium by pH control, with an increase of 16 times of bioavailability comparing
      with free carotenoid. This allowed to potentiate the cytotoxic activity on a
      melanoma cell line by enhancing the water solubility to more than 28 mg/L, and
      present promising applications of SMPMs to provitamins.

PMID- 30273873
TI  - Modulation of membrane properties by silver nanoparticles probed by curcumin
      embedded in 1,2-Dimyristoyl-sn-glycero-3-phosphocholine liposomes.
AB  - Development of nanomaterials has drawn interest on silver nanoparticles (AgNPs),
      which are being incorporated in several biomedical and environmental
      applications, especially anti-bacterial properties of AgNPs has intense
      excitement for their commercial use. However, the impact of AgNPs on cell
      membranes, such as phospholipid membrane properties, is not clearly understood
      yet. By applying curcumin as a probe molecule, this work was done for the first
      time to investigate the effect of AgNPs on membrane properties, such as
      permeability and phase transition temperature using 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC) liposomes as a model for phospholipid membranes. We
      concluded that AgNPs at low concentration decrease the partition of curcumin into
      DMPC liposomes by ~4-fold. In the presence of AgNPs, curcumin was found to be
      located close to the stern layer of DMPC liposomes by using a hydrophobic
      quencher, cetylpyridinium bromide (CPB). In addition, AgNPs broadened the phase
      transition temperature of DMPC liposomes, which ranged from 20  degrees C to 35 
      degrees C.

PMID- 30273874
TI  - Optimising treatment of hyperlipidaemia: Quantitative evaluation of UK, USA and
      European guidelines taking account of both LDL cholesterol levels and
      cardiovascular disease risk.
AB  - BACKGROUND AND AIMS: Guidelines for cholesterol-lowering medication either
      advocate fixed dose statin treatment without low density lipoprotein (LDL)
      cholesterol targets or treatment aimed at LDL cholesterol goals. The decrease in
      LDL cholesterol concentration determines the reduction in atherosclerotic
      cardiovascular disease (CVD) risk. METHODS: As indices of the effectiveness of
      reductions in LDL cholesterol concentration achieved by the various guidelines,
      the number of CVD events prevented in 100 people during 10 years of treatment
      (N100) and the number of people, who must be treated for 10 years to prevent one
      CVD event (NNT), were calculated taking into account both CVD risk and
      pretreatment LDL cholesterol concentration. That our method of calculating NNT
      and N100, could be extended to statin regimens of different intensity or of
      statin combined with adjunctive cholesterol-lowering medication was demonstrated
      by meta-analysis. RESULTS: Reductions in LDL-cholesterol concentration are
      determined by the choice and dose of medication and by the pre-treatment LDL
      cholesterol concentration. At similar CVD risk, whatever cholesterol-lowering
      strategy is adopted, people with higher pre-treatment LDL cholesterol benefit
      more than those with lower levels. Fixed dose statin regimens are less effective
      than target LDL cholesterol levels of 1.8 or 1.4 mmol/l when pre-treatment LDL
      cholesterol levels exceed 4 mmol/l. However, fixed dose statin is more effective
      in people with lower initial LDL cholesterol. The predicted NNT and N100 were
      closely related to the observed reduction in CVD risk in our meta-analysis.
      CONCLUSIONS: In hypercholesterolaemia, aiming for LDL cholesterol targets with
      statin dose titration (and when necessary adjunctive medication) is essential to
      optimise benefit.

PMID- 30273875
TI  - Outlook on optical identification of micro- and nanoplastics in aquatic
      environments.
AB  - Plastic pollution in natural water bodies is an emerging problem that requires
      quick actions. Recently, the role of micro- and nanoplastics in pollution and
      health issues has been realized and taken seriously. In this paper, we have
      studied optical properties, such as NIR spectra and refractive index, of some
      common plastic materials and present a method and data to screen especially
      problematic transparent plastics with rough surface in aquatic environments. We
      also give an outlook of possible optical measurement methods that could be used
      for detection of micro- and nanoplastics.

PMID- 30273876
TI  - Chronic fluoride exposure induces neuronal apoptosis and impairs neurogenesis and
      synaptic plasticity: Role of GSK-3beta/beta-catenin pathway.
AB  - Fluoride is becoming an ineluctable environmental pollutant and its longterm
      exposure would cause fluorosis and irreversible brain damage, but the molecular
      mechanisms remain far from fully understood. In the present study, we firstly
      evaluated the glycogen synthase kinase 3beta (GSK-3beta)/beta-catenin pathway in
      the hippocampus of rats exposed to fluoride, given the well-established role of
      GSK-3beta/beta-catenin pathway in neuronal death and survival. Our data showed
      that sustained exposure to 50 mg/L and 100 mg/L NaF in drinking water dose
      dependently induced neuronal loss and apoptosis in rat hippocampus. Neurogenesis
      was also weakened by fluoride administration in the hippocampal dentate gyrus
      region. Additionally, the synaptic markers, synaptophysin (SYP) and post-synaptic
      density 95 (PSD95) protein levels, were decreased by 100 mg/L NaF treatment,
      whereas 50 mg/L NaF only reduced SYP expression, indicating a compromised
      synaptic function. We further demonstrated that NaF, especially the higher dose,
      induced GSK-3beta activity, with decreased inactive phosphorylated GSK-3beta
      levels and increased GSK-3beta, the active form of the kinase. Correspondingly,
      downstream beta-catenin signaling was undermined by NaF treatment as evidenced by
      the fact that both two doses of NaF decreased nucleus beta-catenin status and the
      higher dose of NaF also reduced cytoplasmic beta-catenin protein expression.
      Taken together, the present study firstly showed the aberrant changes of GSK
      3beta/beta-catenin signaling in the fluoride-exposed brain, highlighting the
      involvement of GSK-3beta/beta-catenin signaling in the fluoride-induced
      neurotoxicity.

PMID- 30273877
TI  - Nutrient limitation determines the suitability of a municipal organic waste for
      phytomanaging metal(loid) enriched mine tailings with a pine-grass co-culture.
AB  - The suitable phytomanaging of mine tailings not only requires an improvement of
      soil fertility but also the assessment of the biotic interactions between the
      selected plant species. This study aimed to evaluate the effect of an organic
      amendment on the response of two plant species of contrasting habit, a tree,
      Pinus halepensis and a grass, Piptatherum miliaceum growing on a metal(loid)
      contaminated substrate collected from mine tailings. Pots containing single plant
      individuals or their combination, with and without organic amendment (at 10%
      rate), were established and grown in a greenhouse for 13 months. Plant biomass,
      foliar ionome, leaf delta15N and metal(loid) concentrations were measured at the
      end of the experiment. The amendment alleviated P deficiency in the substrate and
      strongly stimulated biomass production by both plant species (10-fold for pine;
      90-fold for the grass), leading to more balanced N/P ratios in leaves (especially
      for the grass). Co-culture with the grass negatively affected pine growth,
      decreasing total biomass and leaf delta15N values and inducing severe N
      deficiency (leaf N/P ratio<10). In contrast, co-culture with pine improved the
      nutrient status and growth of the grass, but only under non-amended conditions.
      Needle metal(loid) concentrations in P. halepensis were affected by both
      amendment addition and co-culture with the grass. High biomass growth with low
      metal(loid) concentrations in P. miliaceum leaves for the amended treatment makes
      this grass species suitable for the phytomanagement of metal(loid) polluted
      tailings, since it achieves high biomass production together with low
      concentrations of metal(loid)s in edible/senescent parts.

PMID- 30273878
TI  - A screening test based on hematological and histological biomarkers to evaluate
      the environmental impacts in tambaqui (Colossoma macropomum) from a protected
      area in Maranhao, Brazilian Amazon.
AB  - Nowadays biomonitoring programs can benefit with mathematical models able to
      correlate biomarkers to monitor water pollution. The aim of this study was to
      develop a screening test based on hematological parameters and histological
      lesions in tambaqui (Colossoma macropomum), to allow the assessment of
      environmental impacts on fish inhabiting a protected area in Maranhao inside of
      Brazilian Amazon. Samples collected during three years (2012, 2013 and 2014) were
      grouped by season (dry and rainy) Water samples were also collected for physical
      chemistry analysis. Blood samples were stained with Acridine Orange to detect
      micronuclei and erythrocyte abnormalities. Gill tissues were stained with
      hematoxylin and counterstained with alcoholic eosin, and histopathological
      lesions were scored on a scale of 1-3, being 1 = minimal pathological importance,
      2 = moderate pathological importance and 3 = marked pathological importance. A
      screening test for evaluating environmental impact was developed by fitting the
      measured data (necrosis, erythrocyte abnormalities, number of micronuclei) from
      tambaqui. A three-dimensional surface was fit to the empirical data. Our proposed
      model predicted the probability of necrosis (observed in euthanized animals)
      based on the numbers of micronuclei and abnormal erythrocytes (observed in blood
      samples from live animals) (correlation coefficient R = 0.89). The methodology
      could be applied for predicting contamination histories (chronic pollution that
      induces branchial lesions) in rivers using the micronucleus and erythrocyte
      abnormalities of the fishes (with a simple blood sample).

PMID- 30273879
TI  - The design of a sunlight-focusing and solar tracking system: A potential
      application for the degradation of pharmaceuticals in water.
AB  - Photolysis is considered one of the most important mechanisms for the degradation
      of pharmaceuticals. Photodecomposition processes to remove pharmaceuticals in
      water treatment presently use artificial UV light incorporated in advanced
      oxidation processes. However, UV lighting devices consume a substantial amount of
      energy and have high operational costs. To develop low energy treatment systems
      and make good use of abundant sunlight, a natural energy resource as a green
      technology is needed. As such, a system that combines sunlight focusing, solar
      tracking and continuous reaction was designed and constructed in the present
      study, and its application potential as a pharmaceutical water treatment option
      was tested. Two representative photolabile pharmaceuticals, ciprofloxacin and
      sulfamethoxazole, were chosen as the target pollutants. The results indicate that
      the sunlight-focusing system consisting of a UV-enhancing-coated parabolic
      receiver can concentrate solar energy effectively and hence result in a more than
      40% improvement in the direct photolysis efficiency of easily photoconvertible
      ciprofloxacin. The sunlight-focusing coupled with a solar tracker (SFST) system
      can improve the sunlight-focusing efficiency by more than 2-fold, thus leading to
      the maximization of the efficient use of solar energy. Sulfamethoxazole, which is
      difficult to photoconvert, was successfully degraded by more than 60% compared to
      direct photolysis through the designed SFST system in the presence of persulfate.
      The treatment system exhibited good and consistent performance during clear and
      cloudy days of summer. It is proven that the UV-enhanced coated SFST system with
      the addition of persulfate indeed has development potential for application in
      the degradation of pharmaceuticals in water.

PMID- 30273880
TI  - Graphitic carbon nitride (g-C3N4)-based photocatalysts for water disinfection and
      microbial control: A review.
AB  - Microbial contamination in drinking water is of great concern around the world
      because of high pathogenic risks to humans. Semiconductor photocatalysis has
      aroused an increasing interest as a promising environmental remediation
      technology for water disinfection and microbial control. Among various
      photocatalysts, graphitic carbon nitride (g-C3N4), as a fascinating two
      dimensional conjugated polymer consisting of low-cost, earth-abundant elements,
      has drawn broad attention as a robust, metal-free, and visible-light-active
      material in the fields of both environmental remediation and solar energy
      conversion. Photocatalytic applications of g-C3N4-based nanomaterials for water
      splitting, hydrogen production, carbon dioxide reduction, and pollutant
      degradation have been extensively investigated and systematically reviewed. In
      contrast, their antimicrobial properties have been explored more recently due to
      the complex structure and unique metabolism of living microorganisms compared
      with chemicals. The corresponding rapidly increasing research efforts in the last
      five years have inspired us to conduct the review. This review is the first to
      comprehensively summarize the progress in design and antimicrobial performance of
      g-C3N4-based photocatalysts for water disinfection and microbial control,
      involving not only bacteria but also viruses and microalgae. Moreover, the
      underlying inactivation mechanisms of photocatalysts for microorganisms are
      evaluated to provide further understanding of g-C3N4-based advanced disinfection
      processes. In addition, some exciting future opportunities and challenges at the
      forefront of this research platform are pointed out. It is expected that this
      review can pave a new avenue for the development of a facile, cost-effective,
      environmental-friendly, and sustainable disinfection alternative.

PMID- 30273882
TI  - Abnormal cerebellum-DMN regions connectivity in unmedicated bipolar II disorder.
AB  - OBJECTIVE: Bipolar disorder (BD) is a common psychiatric disease. Previous
      studies have found abnormalities in structural and functional brain connectivity
      in BD patients. However, few studies have focused on the functional connectivity
      (FC) of the cerebellum and its sub-regions in patients with BD. The present study
      aimed to examine the FC of cerebellum-default mode network (DMN) regions in
      patients with BD II. METHOD: Ninety patients with unmedicated BD II depression
      and 100 healthy controls (HCs) underwent resting-state functional magnetic
      resonance imaging. We selected three pairs of subregions of the cerebellum that
      are DMN-related (the bilateral Crus I, Crus II, and lobule IX) as seed regions
      and calculated the whole brain FC for each subregion. RESULTS: Compared with the
      HCs, the patients with BD II depression showed increased connectivity between the
      right Crus I and bilateral precuneus and decreased connectivity between the left
      Crus II and bilateral medial prefrontal cortex (mPFC) and between the left Crus
      II and right medial frontal gyrus (MFG). There was no significant difference in
      the whole FC of the left Crus I and bilateral lobule IX between the BD II
      depression group and the HCs group. LIMITATIONS: This study was cross-sectional
      and did not examine data from euthymic BD patients. CONCLUSIONS: The findings
      showed impaired FC of cerebellum-DMN regions in BD; partial FC between the Crus I
      and precuneus and the Crus II and prefrontal cortex suggests the importance of
      abnormal cerebellum-DMN regions FC in the pathophysiology of BD.

PMID- 30273881
TI  - Insomnia predicts increased perceived burdensomeness and decreased desire for
      emotional support following an in-laboratory social exclusion paradigm.
AB  - BACKGROUND: Research suggests that insomnia is associated with elevated
      perceptions of loneliness and social disconnection; however, few quasi
      experimental studies have tested the relationship between these constructs. This
      study examined whether insomnia symptom severity predicts changes in perceptions
      of interpersonal connectedness and desire for emotional support following in
      laboratory participation in a social exclusion paradigm. METHODS: Young adults (N
      = 70) completed self-report measures assessing constructs of interest before and
      after engaging in a social exclusion paradigm (Cyberball). Linear regression
      analyses were used to evaluate whether baseline insomnia symptom severity
      predicted perceived burdensomeness, desire for emotional support, and thwarted
      belongingness after playing Cyberball; analyses controlled for baseline perceived
      burdensomeness, desire for emotional support, and thwarted belongingness,
      respectively, as well as baseline social anxiety and depression symptoms.
      RESULTS: Greater insomnia symptom severity significantly predicted greater
      feelings of perceived burdensomeness following Cyberball participation, beyond
      baseline perceived burdensomeness, social anxiety symptoms, and depression
      symptoms (beta= .24, p = .001). More severe insomnia symptoms also significantly
      predicted lower desire for emotional support after playing Cyberball, beyond
      baseline desire for emotional support and social anxiety symptoms (beta= -.14, p
      = .03) but not beyond baseline depression symptoms (beta= -.16, p = .07).
      Insomnia symptoms were not significantly associated with thwarted belongingness
      after Cyberball (beta= -.05-.08, p = .27-.57). LIMITATIONS: Replication in larger
      samples and using other sleep disturbance indices is needed. CONCLUSIONS:
      Findings suggest that individuals with more severe insomnia symptoms in the past
      two weeks experience greater perceptions of being a burden on others and less
      desire for emotional support in response to social exclusion.

PMID- 30273883
TI  - Handgrip strength and depression among 34,129 adults aged 50 years and older in
      six low- and middle-income countries.
AB  - INTRODUCTION: Handgrip strength is a simple and inexpensive marker of health and
      mortality risk. It presents an ideal risk-stratifying method for use in low and
      middle-income countries (LMICs). There are, however, no population-based studies
      investigating the associations between handgrip strength and depression in LMICs.
      We aimed to assess these associations among community-dwelling middle-aged and
      older adults using nationally representative data from six LMICs. METHOD: Cross
      sectional data on individuals aged >= 50 years from the World Health
      Organization's Study on Global Ageing and Adult Health were analyzed. Depression
      was based on the Composite International Diagnostic Interview. Weak handgrip
      strength was defined as < 30 kg for men and < 20 kg for women using the average
      value of two handgrip measurements of the dominant hand. Multivariable logistic
      regression analysis was conducted. RESULTS: The sample included 34,129
      individuals (62.4 +/- 16.0 years; 52.1% female). The prevalence of weak handgrip
      strength and depression were 47.4% and 6.2%, respectively. Individuals with weak
      handgrip strength had a higher prevalence of depression than those without this
      condition (8.8% vs. 3.8%; p < 0.001). Across all countries, after adjustment for
      potential confounders, weak handgrip strength was associated with a 1.45 (95%CI =
      1.12-1.88) times higher odds for depression, although some between-country
      differences were noted. DISCUSSION: Weaker handgrip strength is associated with
      higher odds for depression in LMICs. Future research should seek to establish the
      predictive value of this inexpensive measure for clinical use. Furthermore,
      interventional studies should examine if muscular strength can be a target of
      resistance-training interventions to address depressive symptoms in low-resourced
      settings.

PMID- 30273884
TI  - GxE effects of FKBP5 and traumatic life events on PTSD: A meta-analysis.
AB  - BACKGROUND: Twin studies have demonstrated that both genetic and environmental
      factors influence risk for posttraumatic stress disorder (PTSD), and there is
      some evidence supporting the interplay of genes and environment (GxE). Many GxE
      studies within the PTSD literature have focused on genes implicated in the stress
      response system, such as FK506 binding protein 51 (FKBP5). Given inconsistencies
      across GxE literature as a whole, a meta-analysis to synthesize results is
      warranted. METHODS: Studies were identified through PubMed and PsycINFO. A meta
      analysis was conducted using a random effects model in the MAc package in R.
      Heterogeneity of the effect size distribution was examined with Cochran's Q
      statistic. A Simes procedure was used to test the gene-level GxE effect for FKBP5
      interacting with trauma. RESULTS: A significant gene-level GxE gene effect was
      demonstrated for FKBP5 when pooled across all four examined variants (rs1360780,
      rs3800373, rs9296158, rs9470080) when interacting with trauma exposure on PTSD.
      Significant large GxE effect sizes were also found for each independent variant.
      There was no evidence for heterogeneity of variance. LIMITATIONS: Limitations
      include reduced power for detecting variability across moderators, potential bias
      due to failure of meta-analyzed studies to account for two-way covariate x gene
      and covariate x environment influences, and a high false discovery rate that is
      characteristic of GxE analyses. CONCLUSIONS: This is the first study to quantify
      an overall gene-level effect of FKBP5 in a GxE analysis of PTSD, evidence which
      may be used to address current issues in the FKBP5 GxE literature (e.g.,
      disparate variants, low sample sizes and power), as well as inform follow-up
      functional research.

PMID- 30273885
TI  - How many bereaved people hallucinate about their loved one? A systematic review
      and meta-analysis of bereavement hallucinations.
AB  - BACKGROUND: Bereavement hallucinations (BHs) entail a perception of a deceased in
      any sense modality or as a quasi-sensory sense of presence. BHs are an associated
      feature of the proposed Persistent Complex Bereavement Disorder (PCBD) in DSM-5.
      The goals of this review are to estimate the prevalence of BHs, identify possible
      moderators, and review the methodological status of this research field. METHODS:
      A systematic literature search was conducted through the databases PubMed,
      PsycINFO, and CINAHL. Studies systematically assessing the prevalence of BHs of a
      relative or friend were included. RESULTS: Twenty-one eligible studies were
      identified and 8 meta-analyses of BHs in different sense modalities were
      conducted. The prevalence of having one or more BHs was estimated to be 56.6%
      (95% CI 49.9-63.2), and the estimated prevalence of BHs in specific sense
      modalities ranged within 7.0-39.7%. Meta-regression analyses revealed
      associations to age and conjugal bereavement, but results are tentative and
      dependent on the type of BH in question. LIMITATIONS: The included studies were
      methodologically heterogeneous. Limitations included the lack of a valid measure
      of BHs and low sample generalizability. CONCLUSION: This first systematic review
      and meta-analysis of BHs suggests that more than half of the bereaved people
      experience some kind of BH. However, there are considerable methodological
      limitations in the research of BHs, which is of pertinent interest as BHs have
      been linked to the development of a future diagnosis of clinically impairing
      grief. A valid measure of BHs needs to be developed and used in high-quality
      epidemiological research using population-based designs.

PMID- 30273886
TI  - The association of vision loss and dimensions of depression over 12 years in
      older adults: Findings from the Three City study.
AB  - BACKGROUND: The established relationship between vision impairment and depression
      is limited by the examination of depression only as a unidimensional construct.
      The present study explores the vision-depression relationship using a dimensional
      approach. METHODS: 9036 participants aged 65 years and above enrolled in the
      Three-City study were included. Relationships between baseline near Vision
      Impairment (VI) or self-reported distance Visual Function (VF) loss with
      trajectory of four dimensions of depression - depressed affect, positive affect,
      somatic symptoms and interpersonal problems - over 12 years were examined using
      mixed-effects models. Depression dimensions were determined using the four-factor
      structure of the Centre for Epidemiology Studies-Depression Scale (CESD).
      RESULTS: In the fully adjustment models, mild near VI predicted poorer depressed
      affect (b = 0.04, p = .002) and positive affect (b = -0.06, p < 0.001) over time,
      with evidence of longer term adjustment. Distance VF loss was associated with
      poorer depressed affect (b = 0.27, p <= .001), positive affect (b = -0.15, p =
      .002), and somatic symptoms (b = 0.18, p <= .001) at baseline, although only the
      association with depressed affect was significant longitudinally (b = 0.01, p =
      .001). Neither near VI nor distance VF loss was associated with interpersonal
      problems. LIMITATIONS: This paper uses a well-supported model of depression
      dimensions, however, there remains no definite depression dimension model.
      Distance VF loss was self-reported, which can be influenced by depression
      symptoms. CONCLUSIONS: Vision impairment in older adults is primarily associated
      with affective dimensions of depression. A reduction in social connectedness and
      ability to engage in pleasurable activities may underlie the depression-vision
      relationship. Older adults with vision impairment may benefit from targeted
      treatment of affective symptoms, and pleasant event scheduling.

PMID- 30273887
TI  - Associations between broader autism phenotype (BAP) and maternal attachment are
      moderated by maternal postpartum depression when infants are one month old: A
      prospective study of the Japan environment & children's study.
AB  - BACKGROUND: Broader autism phenotype (BAP) refers to the expression of behavioral
      and cognitive dispositions similar to autism spectrum disorder. The present study
      investigated whether mothers' BAP was prospectively associated with maternal
      attachment, and if postpartum depression modified this association. METHODS: The
      Japan Environment and Children's Study (JECS) is a national and government-funded
      birth cohort study that began in January 2011. Among the 103,099 mothers
      enrolled, 87,369 mothers without a history of depression were included in the
      analysis. Self-administered questionnaires were used. These included: the
      Japanese version of the Autism Spectrum Quotient, the Mother to Infant Bonding
      Scale, and the Edinburgh Postnatal Depression Scale. Logistic regression analyses
      were performed. RESULTS: The BAP during the second or third trimester of
      pregnancy was linearly associated with an increased risk of postpartum depression
      and insecure maternal attachment when infants were one month old (p for trend <
      0.001), after adjusting for confounding variables. When stratified by postpartum
      depression, among the BAP subscales, deficiencies in social skills and
      communication were associated with an increased risk of insecure maternal
      attachment in mothers without postpartum depression. The relationships between
      the BAP subscales and maternal attachment were attenuated among mothers with
      postpartum depression. LIMITATIONS: Only five items of the Mother to Infant
      Bonding Scale were used in the present study, and thus the results should be
      interpreted with caution. CONCLUSIONS: Mothers' BAP was predictive of insecure
      maternal attachment toward their infant. Postpartum depression partially
      moderated the associations between mothers' BAP and insecure maternal attachment.

PMID- 30273889
TI  - Applications of peptide hormone ligands for the treatment of dumping and short
      bowel syndrome.
AB  - Dumping syndrome is a common and debilitating complication of upper
      gastrointestinal surgery. Accelerated gastric emptying and dysregulated secretion
      of gastrointestinal (GI) hormones are involved in its pathophysiology.
      Pasireotide, a novel somatostatin analogue, improved dumping in a phase-2 study.
      Preliminary data suggest that the glucagon-like peptide-1 (GLP-1) analogue
      liraglutide can also improve dumping. Short bowel syndrome is the most common
      cause of intestinal failure and involves not only a loss of mucosal absorptive
      area but also hypersecretion and accelerated transit. GLP-2 is the best studied
      hormone involved in intestinal adaptation. An increasing body of evidence
      demonstrates that the GLP-2 analogue teduglutide reduces parenteral support
      needs. New GLP-2 analogues and analogues of other GI hormones such as liraglutide
      are being investigated as promising treatments in short bowel syndrome.

PMID- 30273890
TI  - Developmental trajectories of externalizing behavior from ages 4 to 12: Prenatal
      cocaine exposure and adolescent correlates.
AB  - BACKGROUND: Although prenatal cocaine exposure (PCE) has been linked with greater
      externalizing behavior, no studies have investigated heterogeneity of
      developmental trajectories in children with PCE to date. The present study aimed
      to: (1) identify developmental trajectories of externalizing problems in
      childhood by using a person-oriented analytic approach; (2) examine whether
      trajectories differ by PCE and other environmental and biological correlates; and
      (3) investigate how trajectories were associated with adolescent substance use
      and sexual behavior. METHODS: Adolescents (N = 386; 197 PCE, 187 non-cocaine
      exposed (NCE)), primarily African-American and of low socioeconomic status, were
      prospectively enrolled in a longitudinal study at birth. Externalizing problems
      were assessed with the Child Behavior Checklist (CBCL) at ages 4, 6, 9, 10, 11,
      and 12. Substance (tobacco, alcohol, marijuana) use, via self-report and biologic
      assays, and early (before age 15) sexual intercourse were assessed at age 15.
      RESULTS: Latent class growth modeling indicated four distinctive developmental
      trajectories of externalizing behavior from ages 4 to 12: low-decreasing group
      (32%); moderate-decreasing group (32%); accelerated risk group (14%); and
      elevated-chronic group (22%). PCE and maternal psychological distress
      interactively differentiated developmental trajectories of externalizing
      behavior, which were related to subsequent adolescent substance use and early
      sexual behavior differently across gender. CONCLUSIONS: The two high-risk
      trajectories (accelerated risk and elevated-chronic groups), comprising 36% of
      the sample, identified in the present study may reflect multi-causality of early
      substance use and perhaps greater risk for transition to substance use disorders
      later in development.

PMID- 30273891
TI  - Differential relationships between cannabis consumption and sleep health as a
      function of HIV status.
AB  - BACKGROUND: There is evidence that regular cannabis use has negative effects on
      sleep health. Relative to HIV- populations, HIV + individuals consistently report
      greater sleep impairments. The number of HIV + individuals reporting frequent
      cannabis use, often to treat sleep issues, has significantly increased recently.
      It is unknown, however, if HIV status moderates the association between cannabis
      use and sleep health. The current study, therefore, examines these associations
      in a sample of HIV + and HIV- adults. METHODS: HIV + and HIV- (N = 107)
      individuals completed one laboratory visit. Participants completed a 30-day drug
      use history questionnaire quantifying consumption of cannabis, cigarettes, and
      alcohol, and a sleep health questionnaire. To verify substance use and HIV
      status, participants completed a urine toxicology screening and serology testing.
      RESULTS: HIV + individuals demonstrated lower sleep health than HIV- individuals.
      Linear regressions indicated that HIV status moderated the association between
      total 30-day cannabis consumption and sleep health; cannabis consumption was
      negatively associated with sleep health in HIV-, but not HIV + individuals. This
      interactive effect was significant after examining cigarette/alcohol use,
      depression symptoms, and demographic variables as covariates. CONCLUSIONS: These
      results corroborate studies demonstrating an inverse relationship between sleep
      health and cannabis consumption. This study also suggests that factors other than
      cannabis may be associated with lower sleep health in HIV + individuals. Emerging
      studies suggest that inflammation may mediate effects of cannabis on HIV
      infection. Future studies examining this mechanism are warranted to understand
      cannabis further and sleep in HIV + individuals.

PMID- 30273893
TI  - Elevated C-reactive protein as a predictor of a random one-year clinical course
      in the first ten years of schizophrenia.
AB  - We investigate whether C-reactive protein (CRP) levels could predict the clinical
      course of patients with schizophrenia in a prospective study of 50 stable
      outpatients during a random 1-year period within the first 10 years of illness.
      Positive, negative, depressive, and cognitive symptoms were evaluated. Patients
      with low-grade inflammation (CRP = 3-10 mg/L; 28%) at baseline showed significant
      worsening of PANSS-positive and general psychopathology at 1-year follow-up
      compared with those with CRP <= 3 mg/L. Elevated CRP may be a biomarker of poor 1
      year clinical course in patients with schizophrenia.

PMID- 30273892
TI  - History of childhood emotional abuse predicts lower resting-state high-frequency
      heart rate variability in depressed women.
AB  - Childhood emotional abuse impairs emotion regulation and increases risk for major
      depressive disorder in adulthood. Mounting evidence suggests that decreased
      resting-state high-frequency heart rate variability, an index of parasympathetic
      function, represents a transdiagnostic biomarker of emotion dysregulation. We
      propose that adults with histories of major depressive disorder and childhood
      emotional abuse represent a subpopulation at particularly high risk to exhibit
      deficits in parasympathetic control. The current report compared resting-state
      high-frequency heart rate variability across three groups: (1) depressed women
      who endorsed childhood emotional abuse (N = 11); (2) depressed women without
      childhood emotional abuse (N = 19), and (3) never-depressed women without
      childhood emotional abuse (N = 22). Participants completed childhood trauma self
      reports and assessment of resting-state high-frequency heart rate variability.
      ANCOVAs comparing the three groups after controlling for health-related,
      psychiatric, and respiratory factors were significant. Depressed women with
      childhood emotional abuse exhibited lower high-frequency heart rate variability
      than both groups without childhood emotional abuse (d's ranging from 0.81-0.92).
      Surprisingly, psychiatric factors were non-significant predictors, indicating
      that childhood emotional abuse may have a unique impact on autonomic functioning.
      Future research on larger samples is needed to disentangle the relative and
      synergistic burdens of depression and childhood trauma on physiologic indicators
      of emotion dysregulation.

PMID- 30273894
TI  - Childhood emotional abuse and neglect in obese patients with and without binge
      eating disorder: Personality and psychopathology correlates in adulthood.
AB  - The link between childhood traumatic experiences such as sexual and physical
      abuse and EDs in adulthood has been widely demonstrated. To date, however, little
      research focused on the association between emotional abuse and neglect in
      childhood and Binge Eating Disorder (BED) and obesity in adulthood. We enrolled
      127 patients [84 with BED and 43 obese] and 45 healthy controls (HCs). All
      participants were administered the same battery of psychometric tests. Between
      group differences were explored and the relationship between emotional abuse and
      neglect in childhood and personality and psychopathology in adulthood was tested.
      Obese patients showed higher scores in emotional abuse and neglect and sexual
      abuse when compared to HCs. Within obese participants, those with BED reported
      higher emotional abuse and emotional neglect than obese without BED and HCs; the
      BED group differed in physical and sexual abuse from obese participants. The
      association between traumatic experiences in childhood and obesity in adulthood
      has been confirmed independently of the type of trauma. Therapists should take
      into account the traumatic etiology of BED, in particular psychological abuse,
      even in those patients who do not recall physical or sexual abuses. Specific
      techniques to approach traumatic experiences could be applied to BED or non-BED
      patients.

PMID- 30273888
TI  - PanCareLIFE: The scientific basis for a European project to improve long-term
      care regarding fertility, ototoxicity and health-related quality of life after
      cancer occurring among children and adolescents.
AB  - AIMS: Survival after cancer diagnosed during childhood or adolescence continues
      to improve with new treatments and supportive therapies. Optimal long-term care
      requires that risks to vulnerable organs are clearly defined and translated into
      guidelines that are implemented into practice. PanCareLIFE is a pan-European
      consortium that addresses survivorship issues comprising fertility, hearing
      impairment and quality of life. This article describes the scientific basis of
      PanCareLIFE's studies. METHODS: PanCareLIFE involves 17 partner institutions from
      eight European countries, with additional 11 data providers from five other
      countries. Study designs and methods include molecular genetic, cohort and case
      control studies, a longitudinal study and an intervention study. Ethics and data
      protection issues have been taken into account from the beginning. RESULTS:
      PanCareLIFE will investigate the way that treatment impairs female fertility, by
      evaluating anti-Mullerian hormone levels and the underlying genetic
      susceptibility to loss of fertility. For our fertility studies, more than 6000
      survivors have completed questionnaires, more than 1500 provided serum samples
      and more than 400 case-control triads have been identified. Fertility
      preservation guidelines for boys and girls will be developed. More than 2000
      survivors have contributed audiograms for the ototoxicity study. Almost 1000
      samples were sent for genetic analysis related to ototoxicity and gonadal
      reserve. The SF-36 questionnaire will measure quality of life in more than 10,000
      survivors. CONCLUSIONS: The large number of subjects enrolled in PanCareLIFE and
      the detailed information accumulated will allow in-depth evaluation of important
      outcomes. Fertility preservation guidelines will help patients and their families
      make informed decisions and contribute to their long-term well-being.

PMID- 30273895
TI  - Associations between TV viewing, sitting time, physical activity and insomnia
      among 100,839 Brazilian adolescents.
AB  - Our aim was to examine the relationship between insomnia and levels of physical
      activity (PA) and time spent sitting and TV viewing among Brazilian adolescents.
      Data from the Brazilian Scholar Health Survey, a nationally representative survey
      of 9th grade adolescents [mean: 14.28 years (range: 11-18 years)] conducted in
      2015 (n = 100,839) were used. Self-reported insomnia, TV viewing, sitting time
      and total PA (adapted International PA Questionnaire) were collected.
      Chronological age, race, type of city (capital or interior) country region,
      goodies ingestion and ultra-processed foods ingestion were covariates. Logistic
      regression analyses were conducted to assess the associations. A higher sitting
      time and TV viewing (>=8 h/day) was associated with a higher risk of insomnia
      among boys [sitting time: OR = 2.39 (95%CI = 1.88-3.04); TV:OR = 2.49(95%CI =
      1.92-3.22) and girls [sitting time: OR = 2.17(95%CI = 1.84-2.57; TV:OR =
      1.72(95%CI = 1.44-2.04)]. More than 4 h of sitting time per day was associated
      with higher risk of insomnia in adolescents who comply [boys: OR = 1.43(95%CI =
      1.19-1.73); girls: OR = 1.66(95%CI = 1.41-1.94)] and who do not comply with the
      300 min/week of physical activity recommendation [boys = OR = 1.35(95%CI = 1.13
      1.60); girls: OR = 1.38(95%CI = 1.20-1.57)]. Our data suggest that higher levels
      of TV viewing or sitting are associated with sleep difficulties in this large
      cohort of adolescents, irrespective of their physical activity behavior.

PMID- 30273896
TI  - Comparing cognitive clusters across first- and multiple-episode of psychosis.
AB  - Cognitive impairments in psychotic disorders (PD) present heterogeneously across
      patients. Between 2 and 5 clusters have been identified in previous studies with
      first-episode (FEP) and multiple-episodes of psychosis (MEP) patients suggesting
      different profiles of impairment. Past findings suggest there are differences
      between FEP and MEP patients regarding severity and number of affected cognitive
      domains. Heterogeneity of cognitive deficits in PD has perhaps hindered our
      understanding of their course. The present study compared non-affective FEP and
      MEP patients to assess whether illness chronicity could influence cognitive
      impairment profiles. We analyzed cognitive data, collected with the Cogstate
      Schizophrenia Battery, of FEP and MEP patients using cluster analysis. We
      compared clustering methods to obtain a more robust solution. For FEP patients,
      data were collected at their entry to a specialized clinic; the MEP group
      consisted of in- and outpatients. Results suggested cognitive heterogeneity was
      similar in FEP and MEP samples, although in different proportions. Three clusters
      were identified as the most stable solution and comprised groups of patients with
      either 1- no cognitive impairment (over-representation of FEP), 2- generalized
      deficits (over-representation of MEP), or 3- intermediate impairments. These
      findings encourage early interventions adapted to the profile of impairment.

PMID- 30273897
TI  - Biomarkers of adverse childhood experiences: A scoping review.
AB  - Adverse Childhood Experiences (ACEs) are stressful and/or traumatic experiences
      that occur during childhood. Research has demonstrated a link between ACEs and
      risk of physical and mental health disorders, where early life adversity may
      become "biologically embedded" and have wide-ranging effects on various
      physiological systems. The aim of this study was to identify the extent and
      breadth of recent research activity relating to biological measures of ACEs in
      adulthood. We undertook a scoping review including published research articles.
      Medline and PsycINFO were searched for articles from 2007 to July 2017. Articles
      were eligible if they included adult participants, were written in English, and
      reported on a biomarker of childhood adversity in adulthood. Forty articles met
      our inclusion criteria. Studies investigated a range of ACEs that were often
      measured retrospectively. The studies identified biomarkers related to
      inflammation (e.g., CRP), cardio/metabolic systems (e.g., BMI), genetics (e.g.,
      telomere length), and endocrine systems (e.g., cortisol), as well as composites
      of multiple physiological systems. However, not every study identified found
      significant associations. Health behaviours, emotional distress, social
      relationships, and socioeconomic factors may help explain some of these
      associations. Further research is needed to better understand biomarkers of ACEs
      in adulthood and their relationship to health conditions.

PMID- 30273898
TI  - Diagnostic differences in verbal learning strategies and verbal memory in
      patients with mood disorders and psychotic disorders.
AB  - A better understanding of verbal learning strategies can offer insight to the
      difference in verbal memory performance and learning between patients with
      schizophrenia and schizoaffective disorders, non-psychotic major depression, and
      psychotic major depression. To date, a comparison of the use of verbal learning
      strategies and verbal memory performance amongst these specific diagnostic groups
      has not been investigated. This study examined differences in verbal learning and
      memory between psychotic major depression (n = 31), nonpsychotic major depression
      (n = 30), and schizophrenia spectrum disorders (n = 17) disorders. Verbal
      learning and memory were assessed through the use of the California Verbal
      Learning Test-II (CVLT-II). Correlations and multiple regression analyses were
      conducted to analyze differences in verbal learning and memory amongst these
      groups. There were no significant differences in the use of Semantic Clustering.
      Diagnostic differences were observed in the use of Serial and Subjective
      Clustering. The psychotic major depression group utilized Serial Clustering
      strategy significantly less than the nonpsychotic major depression group.
      Learning strategies significantly predicted learning and recall. These findings
      lend support to the hypothesis that learning strategies predict verbal memory
      performance across diagnostic groups. The present study contains useful
      information on diagnostic differences in verbal learning and memory, and a
      framework by which treatment could be tailored to enhance learning specific to
      these diagnostic groups.

PMID- 30273899
TI  - Anxious and alert? Hypervigilance in social anxiety disorder.
AB  - The vast majority of research on attentional biases to threat focusses on
      selective attention, even though several cognitive-behavioral models furthermore
      assume hypervigilance to be important in this regard. Thus, the current study
      examined hypervigilance in trait and state social anxiety. We analyzed visual
      scanpath lengths and fixation counts of participants with Social Anxiety Disorder
      (SAD) (n = 61) and healthy controls (n = 60) in a combined visual search and eye
      tracking paradigm, including photographs of facial expressions. Half of all
      participants were randomly assigned to a state anxiety induction. Interaction
      effects revealed opposed attentional patterns of participants with SAD as
      compared to healthy controls considering overall visual scanpath lengths
      (F(1,117) = 5.32, p = 0.023, eta2partial = 0.043) and fixation counts (F(1,117) =
      5.10, p = 0.026, eta2partial = 0.042). Accordingly, participants with SAD showed
      signs of hypervigilance in the anxiety induction condition. In contrast, there
      was no main effect of diagnostic group, indicating that individuals with SAD
      shift their attentional focus to broad scanning behavior only under conditions of
      threat. Our results add to the small number of existing studies on hypervigilance
      in SAD and suggest the topic to be promising for future research.

PMID- 30273900
TI  - Association between neurological soft signs and antioxidant enzyme activity in
      schizophrenic patients.
AB  - To determine the relationship between alterations in the activity of the enzymes
      participating in antioxidative defense system and neurological soft signs (NSS)
      in schizophrenic patients with the first episode psychosis (SFE, n = 19),
      patients in relapse (SR, n = 46), and healthy controls (HC, n = 20). NSS
      intensity and enzymatic plasma activities of superoxide dismutase (SOD), catalase
      (CAT), and glutathione peroxidase (GPX) were compared between SFE, SR and HC
      subjects and a follow-up correlation analyses between the enzyme activities and
      NSS intensity was performed. NSS intensity was increased four times in
      schizophrenic patients compared with healthy controls. Activities of SOD and CAT
      were 40% decreased in SFE and these reductions were ameliorated by antipsychotic
      treatment. GPX activity was 20% decreased in both patient groups compared with
      controls. A negative correlation between NSS intensity and GPX activity was
      specifically found in the SFE patients. The data in this report argue that a
      reduction of GPX activity might be one of the causes for the emergence of NSS at
      the onset of schizophrenia, and provide the evidence that antipsychotic therapy
      can attenuate activity reductions of SOD and CAT, but not the activity reduction
      of GPX and the intensity of NSS.

PMID- 30273901
TI  - A randomized controlled trial on a smartphone self-help application (Be Good to
      Yourself) to reduce depressive symptoms.
AB  - Depressive symptoms are common, yet only a subgroup of individuals receive
      adequate treatment. To reduce the treatment gap, several online self-help
      programs have been developed, yielding small to moderate effects. We developed a
      smartphone self-help application addressing depressive symptoms. We sought to
      evaluate its feasibility and efficacy in participants reporting a subjective need
      for help (a diagnosis of depression was not mandatory). We conducted a randomized
      controlled trial (N = 90). The primary outcome was a reduction of depressive
      symptoms measured with the Patient Health Questionnaire-9 (PHQ-9). Secondary
      outcomes included improved self-esteem (Rosenberg Self-Esteem Scale) and quality
      of life (WHOQOL-BREF). The intervention group obtained access to the application
      for four weeks, the wait-list group received access after the post assessment. No
      group differences emerged in either outcome in intention-to-treat analyses. Per
      protocol analyses with frequent users (i.e., several times a week or more)
      yielded a small effect size (eta2p = 0.049) at trend level on the reduction of
      depressive symptoms in favor of the treatment group. However, 39% of the
      participants did not use the application frequently. Mobile self-help
      applications represent a promising addition to existing treatments, but it is
      important to increase patients' motivation to use them.

PMID- 30273902
TI  - Study on the optical properties of the magnetic circuit corner shape of the
      magnetic lens.
AB  - In this paper, we aim to improve the optical properties of magnetic lenses in
      transmission electron microscope(TEM). First, the mathematical model of the
      magnetic field is established, and the formula of the reluctance of the magnetic
      lens at the corner of the magnetic circuit is deduced. The calculation results of
      the reluctance are obtained by the numerical analysis method. Then, we find that
      the corner reluctance affects the density distribution of the magnetic flux lines
      at the corner. Therefore, the structural shape of the corner of the magnetic lens
      is optimized. The magnetic flux density on optical axis and the corresponding
      electron optical parameters are obtained by calculations and simulations. The
      optical properties of the magnetic lens are improved after the optimization.

PMID- 30273903
TI  - Thirty-day outcomes in patients with acute pulmonary embolism who discontinued
      anticoagulant therapy before 90 days.
AB  - BACKGROUND: The contemporary natural history of patients with acute pulmonary
      embolism (PE) not receiving (or early discontinuing) anticoagulant therapy has
      not been consistently evaluated. OBJECTIVE: To assess the rate of the composite
      outcome of PE-related death, sudden death, or recurrent thromboembolism (VTE)
      within 30 days in all PE patients in whom anticoagulation was not administered or
      discontinued prematurely (<90 days of anticoagulation). METHODS: We used the
      RIETE database to assess the incidence rates (per 100 person-days) of the
      composite outcome within the subsequent 30 days. The risk of these events was
      compared to PE patients who were anticoagulated for >=90 days. RESULTS: Of 34,447
      PE recruited from 2001 to 2017, 47 (0.14%) did not receive anticoagulants and
      1348 (3.91%) discontinued it before 90 days. Fatal PE developed in 25 (53%) of
      those without any anticoagulation and in 45 (3.33%) with premature
      discontinuations. Sudden death or non-fatal recurrent VTE occurred in 6 (0.45%)
      and 24 (1.48%) patients, respectively. The incidence of the primary outcome
      declined logarithmically from 6.36 per 100 patient-days in untreated patients to
      0.32-0.13 in those treated for 8-90 days. During the first week of follow-up, the
      incidence rate was 13.9 and 0.60-0.31 per 100 patient-days, respectively. The
      adjusted odds of the primary outcome was 27 fold higher in untreated than in
      treated patients, and progressively decreased to 2.5-7 fold higher in patients
      treated for at least 7 days. CONCLUSION: The incidence of the composite outcome
      was highest during the first week, and inversely and logarithmically correlated
      with the duration of anticoagulant therapy.

PMID- 30273904
TI  - Accurate 13-C and 15-N molecular crystal chemical shielding tensors from fragment
      based electronic structure theory.
AB  - Standard nuclear magnetic resonance (NMR) spectroscopy experiments measure
      isotropic chemical shifts, but measuring the chemical shielding anisotropy (CSA)
      tensor can provide additional insights into solid state chemical structures.
      Interpreting the principal components of these tensors is facilitated by first
      principles chemical shielding tensor predictions. Here, the ability to predict
      molecular crystal CSA tensor components for 13C and 15N nuclei with fragment
      based electronic structure techniques is explored. Similar to what has been found
      previously for isotropic chemical shifts, the benchmarking demonstrates that
      fragment-based techniques can accurately reproduce CSA tensor components. The use
      of hybrid density functionals like PBE0 or B3LYP provide higher accuracy than
      generalized gradient approximation functionals like PBE. Unlike for planewave
      density functional techniques, hybrid density functionals can be employed
      routinely with modest computational cost in fragment approaches. Finally, good
      consistency between the regression parameters used to map either isotropic
      shieldings or CSA tensor components is demonstrated, providing further evidence
      for the quality of the models and highlighting that models trained for isotropic
      shifts can also be applied to CSA tensor components.

PMID- 30273905
TI  - Alterations of MEK1/2-ERK1/2, IFNgamma and Smad2/3 associated Signalling pathways
      during cryopreservation of ASCs affect their differentiation towards VSMC-like
      cells.
AB  - Vascular smooth muscle cells (VSMCs) play essential roles in regulating blood
      vessel form and function and they are required for vascular tissue regeneration.
      Multipotent adipose derived stromal cells (ASCs) can be differentiated into VSMC
      like cells, which can be used as a potential VSMC source for the development of
      vascular tissue. However, the effects of cryopreservation on the differentiation
      of ASCs towards VSMCs are poorly studied to date. This study compared fresh ASCs
      (FA) vs. cryopreserved ASCs (CA) with respect to their differentiation potential
      towards VSMC-like cells. The expression of contractile VSMC markers (such as
      smoothelin) and cell contractility were investigated. It was found that VSMC-like
      cells derived from CA expressed smoothelin gene and protein at lower levels and
      showed compromised contractility in response to vasoconstrictors, when compared
      with those derived from FA. Moreover, it was demonstrated that this negative
      effect of cryopreservation could be mediated by MEK1/2-ERK1/2, IFNgamma and
      Smad2/3 associated Signalling pathways. Treatment of CA with MEK1/2-ERK1/2
      activator or IFNgamma neutralizing antibodies enhanced Smad2/3 phosphorylation
      and showed a rescue of the negative effect of cryopreservation on the
      differentiation of ASCs towards VSMC-like cells. These findings are important for
      defining approaches that may use cryopreserved ASCs for vascular tissue
      regeneration.

PMID- 30273906
TI  - Locking plate osteosynthesis for a femoral fracture and subsequent nonunion in a
      patient with osteopetrosis.
AB  - INTRODUCTION: Osteopetrosis is a skeletal disorder characterized by increased
      osteodensity and a remodeling defect. The fragility of dense sclerotic bones may
      lead to an increased incidence of fractures. Although internal fixation can be
      performed, technical challenges may be experienced because of the increased bone
      density. Complications such as delayed union, nonunion, or implant failure may
      occur postoperatively. PRESENTATION OF CASE: We describe a patient with autosomal
      dominant osteopetrosis type 2 who suffered a shaft fracture below a plate of his
      right femur. We performed osteosynthesis with a single locking plate. Union was
      delayed, and plate breakage occurred along with nonunion of the fracture. The
      nonunion was addressed using double locking plates, which secured fixation and
      allowed complete fracture healing. DISCUSSION: There were three reasons of
      nonunion in our case. First, we left gaps between the fragments. Second, we used
      mainly cerclage wires, rather than screws, for plate fixation, which led to
      inadequate stability. Third, the patient was large (height 167 cm, weight 93.1
      kg), so the single plate provided insufficient fixing force. We then used double
      locking plates and attained stronger internal fixation with complete fracture
      healing. CONCLUSION: Double plating with locking plates may be an effective
      treatment option for femoral fractures in patients with osteopetrosis.

PMID- 30273907
TI  - A rare case of gradual enlargement of a multifocal myelolipoma of the posterior
      mediastinum for 12 years after surgical resection of an adrenal myelolipoma.
AB  - INTRODUCTION: A myelolipoma is a rare benign tumor that is composed of adipose
      tissue and hematopoietic elements. Myelolipomas most commonly occur in the
      unilateral adrenal gland. Posterior mediastinal myelolipomas are extremely rare.
      We herein present a rare case of a multifocal myelolipoma of the mediastinum that
      gradually enlarged over a 12-year period after surgical resection of an adrenal
      myelolipoma. This is the first report of multifocal myelolipomas of the posterior
      mediastinum and adrenal gland. PRESENTATION OF CASE: A posterior mediastinal
      tumor was incidentally found by chest X-ray and computed tomography (CT)
      examination of a 74-year-old woman. The patient had a medical history of
      resection of a myelolipoma of the left adrenal gland 12 years earlier. We
      performed tumor extirpation under video-assisted thoracic surgery (VATS). The
      size of the tumor was 4.5 cm, and the postoperative diagnosis was a myelolipoma.
      DISCUSSION: Posterior mediastinal myelolipomas are extremely rare, and only 39
      cases of mediastinal myelolipoma have been reported to date. No reports have
      described a multifocal myelipoma of mediastinal myelolipoma. To our knowledge,
      this is the first report of multifocal myelipomas of the adrenal gland and
      posterior mediastinum. CONCLUSION: A differential diagnosis of myelolipoma of the
      posterior mediastinum is important in patients with a history of myelolipoma of
      the adrenal gland.

PMID- 30273908
TI  - Hepatic myomatous angiomyolipoma diagnosedpreoperatively from specific imaging
      features: A case report.
AB  - INTRODUCTION: Hepatic angiomyolipoma is a rare tumour and is difficult to obtain
      the accurate diagnosis preoperatively because the imaging features are similar to
      hepatocellular carcinoma. PRESENTATION OF CASE: We present a case study of an 80
      year old woman with a liver tumour measuring 6.2 cm * 6.0 cm. We were able to
      diagnose the tumour preoperatively as a rare hepatic myomatous angiomyolipoma
      based on the presence of early venous return evident on angiography and small low
      intensity areas corresponding to fat within the tumour revealed by out-of-phase
      EOB-MRI. The tumour was removed by minimally invasive surgery and our
      preoperative diagnosis was confirmed by positive immunoreactivity for both
      angiomyolipoma-specific human melanoma black 45 and smooth muscle cell positivity
      for melanin. DISCUSSION: We consider that the information obtained in this case
      will be useful for preoperative diagnosis of other hepatic angiomyolipomas, thus
      facilitating more appropriate and less invasive surgery and improving the overall
      outcome. CONCLUSION: Hepatic myomatous angiomyolipoma is a rare tumour. We
      illustrated the two specific imaging features to diagnose it preoperatively.

PMID- 30273909
TI  - Case: Authentic multimodal therapy and liver resection for an initially
      unresectable intrahepatic cholangiocarcinoma.
AB  - INTRODUCTION: Although curative resection is an outstanding prognostic factor of
      intrahepatic cholangiocarcinoma (ICC), certain segments remain unresectable. The
      standard therapy for initially unresectable ICC is uncertain. In this case
      report, we reported the feasibility of multimodal chemotherapy and curative
      resection. CASE: A 59-year-old Asian woman with back pain was referred to the
      hospital by her family physician regarding liver mass visible on ultrasonography.
      At admission, the carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9
      (CA19-9) levels were high, and images showed characteristic signs of ICC with
      intrahepatic metastases and invasions to on the right Glisson's sheath.
      Multimodal therapy was applied to the ICC, which could not be resected at first.
      The therapy comprised hepatic arterial chemoembolization with drug-eluting beads
      (DEB-TACE), angiographic subsegmentectomy (AS), and systemic chemotherapy.
      Downstaging of the ICC, which results in curative resection, was planned due to
      non-normalization of the tumor markers, and pathological analysis revealed
      complete remission. At 34 months after the surgery, the patient was alive without
      relapse. DISCUSSION: Recently, chemotherapy and/or an interventional approach
      were reported to be feasible, although unresectable advanced ICC has a poor
      prognosis. Some studies have reported that multimodal chemotherapy and R0
      resection of initially unresectable ICC can prolong survival time. However, some
      reports have shown high morbidity and mortality associated with initially
      unresectable ICC treated with multimodal chemotherapy and R0 resection. Our study
      resulted in complete remission without complications. CONCLUSION: Multimodal
      chemotherapy and hepatic curative resection on locally advanced ICC are feasible
      treatment approaches for initially unresectable ICC.

PMID- 30273910
TI  - Right-to-left ventricular end diastolic diameter ratio in severe sepsis and
      septic shock.
AB  - PURPOSE: The ratio of right ventricular end-diastolic diameter (EDD) to left
      ventricular EDD (RV/LV) is a measure predictive of right ventricular failure. We
      hypothesized that an increase in RV/LV would be associated with poor prognosis in
      severe sepsis and septic shock. MATERIALS AND METHODS: This is a retrospective
      chart review of patients with severe sepsis and septic shock admitted to a
      medical intensive care unit (ICU) at a single tertiary care hospital. Patients
      were identified by ICD-9 codes: 995.92 for severe sepsis and 785.52 for septic
      shock; and had to have an echocardiogram within 48 h of ICU admission. Increased
      RV/LV was defined as RV/LV >= 0.9. Left and right-sided chamber dimensions were
      measured according to American Society of Echocardiography guidelines. RESULTS:
      We included 146 consecutive ICU patients admitted with septic shock (72) or
      severe sepsis (74). There was no significant difference in ICU mortality in
      patients with RV/LV >= 0.9 versus RV/LV < 0.9 (p = .49). CONCLUSIONS: An
      increased RV/LV does not predict mortality in severe sepsis or septic shock.

PMID- 30273911
TI  - Bioinspired Anti-digestive Hydrogels Selected by a Simulated Gut Microfluidic
      Chip for Closing Gastrointestinal Fistula.
AB  - The anti-digestive features given to hydrogels can prolong their action time in
      gut environment; however, these types of hydrogels have rarely been reported.
      Inspired by indigestibility of dietary fibers, we introduced an injectable
      covalent hydrogel through photopolymerization of glycidyl methacrylate-modified
      xanthan. This newly synthesized hydrogel exhibited a specific concentration
      dependent porosity, swelling ratio, and stiffness. The intestinal epithelial
      cells-6 could grow on the surface of the stiffer hydrogel, and achieved their gut
      barrier functions. A simulated gut microfluidic chip was manufactured to
      demonstrate the hydrogel's good performance of anti-digestion compared with the
      current product, fibrin sealant. Furthermore, calcium ions could induce the
      swelling-shrinking behavior of the hydrogel, which assisted in removing the
      hydrogels at the proper time so as to avoid the mismatch of hydrogel degradation
      and tissue regeneration. Therefore, this hydrogel is expected to be an
      outstanding gut repair material, especially for closing gastrointestinal fistula.

PMID- 30273912
TI  - KInhibition: A Kinase Inhibitor Selection Portal.
AB  - Protein kinases constitute a large class of signaling molecules frequently
      targeted in research and clinical uses. However, kinase inhibitors are
      notoriously non-specific, making it difficult to select an appropriate inhibitor
      for a given kinase. Available data from large-scale kinase inhibitor screens are
      often difficult to query. Here, we present KInhibition
      (https://kinhibition.fredhutch.org), an online portal that allows users to search
      publicly available datasets to find selective inhibitors for a chosen kinase or
      group of kinases. Compounds are sorted by a KInhibition Selectivity Score,
      calculated based on compounds' activity against the selected kinase(s) versus
      activity against all other kinases for which that compound has been profiled. The
      current version allows users to query four datasets, with a framework that can
      easily accommodate additional datasets. KInhibition represents a powerful
      platform through which researchers from broad areas of biology, chemistry, and
      pharmacology can easily interrogate large datasets to help guide their selection
      of kinase inhibitors.

PMID- 30273913
TI  - A review on the abuse of three NPS (synthetic cannabinoids, kratom, poppers)
      among youths in Asia.
AB  - Abuse of new psychoactive substances (NPSs) among youths is increasing at an
      unprecedented rate all over the world. In Asia, abuse of synthetic cannabinoids
      (SCs), kratom, and poppers has been reported, but up to date information related
      to abuse of these three NPSs is lacking. This literature review focuses on the
      recent abuse of these three NPS among Asian youth. Many studies have been
      conducted to investigate the abuse statuses of SCs in Asian youth in Turkey,
      Japan, and Korea, and many cases of kratom abuse have been reported in Malaysia
      and Thailand. In addition, concerns have been expressed about the use of kratom
      in combination with other substances by teenagers. Popper abuse has been reported
      among many young people in Asia, including Korea and China, and many studies on
      popper abuse have focused on men who have sex with men in China and Malaysia.
      Since NPS abuse can have severe adverse effects and create social problems, there
      is a continuing need to investigate NPS abuse status continuously among young
      people.

PMID- 30273914
TI  - Estimation of stature from dimensions of the fourth lumbar vertebra in
      contemporary middle-aged Finns.
AB  - BACKGROUND: Accurate stature estimation plays an essential role in the
      identification of unknown deceased individuals. For cases in which conventional
      methods of stature estimation are not applicable, we studied the stature
      estimation potential of the fourth lumbar vertebra (L4) among a large living
      sample of representative contemporary Finns. We also generated stature estimation
      equations for the middle-aged Finnish population. MATERIAL AND METHODS: Our study
      population comprised the Northern Finland Birth Cohort 1966 for which lumbar
      magnetic resonance imaging (MRI) scans and objective measurements of stature were
      available from midlife (n=1358). After screening the MRI scans for vertebral
      pathologies, we measured the maximum and minimum widths, depths and heights of
      the L4 body with high precision and reliability. We then calculated their sums
      and means together with approximations of vertebral cross-sectional area and
      volume. By constructing simple and multiple linear regression models around the
      L4 parameters, we generated equations for stature prediction, and investigated
      their accuracy on the basis of the adjusted R squared (R2) and standard error of
      the estimate (SEE) values of the models. RESULTS: The multiple linear regression
      models of the mean width, depth and height of L4 yielded the highest prediction
      accuracies with the lowest prediction errors (for the entire sample, R2=0.621 and
      SEE=5.635cm; for men, R2=0.306 and SEE=5.125cm; for women, R2=0.367 and
      SEE=4.640cm). CONCLUSION: When conventional methods for estimating stature are
      not applicable, the lumbar vertebrae may be utilized for this purpose. Relatively
      accurate stature estimates can be given on the basis of only L4 dimensions.

PMID- 30273915
TI  - A new ligand of CD105 screened out by phage display technology provides a
      reliable identification of recurrent or metastasizing pleomorphic adenoma from
      pleomorphic adenoma.
AB  - OBJECTIVES: To assess CD105 expression in pleomorphic adenoma (PA), recurrent
      pleomorphic adenoma (RPA) and metastasizing pleomorphic adenoma (MPA), to
      identify new epitopes and screen a ligand with high affinity to CD105 by phage
      display technology, to evaluate the reliability of the new ligand for identifying
      RPA/MPA from PA. METHODS: Phage display technology was used to screen ligands
      with high affinity to recombinant human CD105. The ligand with strongest affinity
      to CD105 was synthesized by FMOC Chemistry according to the sequencing results.
      The archived formalin fixed paraffin-embedded (FFPE) tissues of 35 PA cases, 12
      RPA cases and 2 MPA cases were sliced and immunofluorescent stained. CD105
      expression were detected by Confocal laser scanning microscopy (CLSM). The
      relative fluorescence intensity was calculated with the image processing software
      Image J. Statistical analyses were performed by the software Graph Pad Prism
      (Version 7.0a). Using PROC logistic, receiver operating characteristic (ROC)
      curves, area under ROC curves (AUCs) were generated to assess the sensitivity and
      specificity of the new ligand for identifying RPA/MPA from PA cases. RESULTS: A
      ligand with specialty and high affinity to CD105 i.e. ligand nABPK296 were
      developed. FITC-labeled ligand nABPK296 confirmed the difference of CD105
      expression in RPA/MPA and PA. The AUC of nABPK296 was 0.9418. CONCLUSIONS: CD105
      is a promising biomarker for identification of RPA/MPA from PA cases. Ligand
      nABPK296 provides a promising approach to CD105 detection. This study also
      validated the reliability of phage display technology in finding new episodes and
      ligands with high affinity for antigens.

PMID- 30273916
TI  - Changes in the function and phenotype of resident peritoneal macrophages after
      housing in an enriched environment.
AB  - Exposure to an enriched environment (EE) affects not only brain functions but
      also immune responses upon viral or bacterial infections. In this study, we
      examined changes in the phagocytic response and chemokine production of resident
      peritoneal macrophages after mice had been housed under EE conditions for 6 or 8
      weeks, and then explored the possibility that EE could cause a change in the
      macrophage phenotype by means of flow cytometry as well as quantitative RT-PCR.
      The percentages of EE macrophages phagocytosing S. aureus and apoptotic
      neutrophils were significantly larger than those of standard environment (SE)
      macrophages. After coculturing with S. aureus, EE macrophages tended to produce
      greater amounts of chemokines such as MIP-2, KC and MCP-1 than SE ones, although
      the increases for MIP-2 and KC were not statistically significant. As compared
      with SE macrophages, EE macrophages included more CD40-positive cells (M1
      marker), and expressed more mRNAs of IL-6 (M1 marker) and IRF4 (M2 marker), and
      less mRNA of CD38 (M1 marker), suggesting either the possibility that EE
      macrophages are a mixed population of M1 and M2 macrophages or the possibility
      that they are a unique population with a mixed M1 and M2 macrophage phenotype.

PMID- 30273917
TI  - Leonurine inhibits IL-1beta induced inflammation in murine chondrocytes and
      ameliorates murine osteoarthritis.
AB  - Osteoarthritis (OA) is a chronic degenerative joint disease characterized by
      cartilage degradation, subchondral bone sclerosis and synovitis. Leonurine, an
      active component extracted from the leaves of Herba leonuri, has been reported to
      possess various potent biological effects such as anti-oxidant, anti-apoptosis,
      and anti-inflammatory. However, the therapeutic benefits of leonurine on OA have
      not been reported. This study aimed to evaluate the therapeutic effect of
      leonurine on chondrocytes and in murine OA models. Murine chondrocytes were pre
      treated with leonurine (5, 10, and 20 MUM) for 2 h and then stimulated with IL
      1beta for 24 h. Production of NO, PGE2, IL-6, TNF-alpha, MMP-3, MMP-13, and
      ADAMTS-5 was assessed with the Griess reagent and ELISAs. The mRNA expression of
      COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5, aggrecan, and collagen-II was tested with
      real-time polymerase chain reaction. The protein expression of iNOS, COX-2 and NF
      kappaB-related signaling molecules was measured with western blotting. In this
      study, leonurine visibly inhibited the IL-1beta-induced production of NO, PGE2,
      IL-6 and TNF-alpha; and decreased the expression of iNOS, COX-2, MMP-3, MMP-13
      and ADAMTS-5 in chondrocytes. Furthermore, leonurine significantly suppressed IL
      1beta-stimulated NF-kappaB activation. In addition, treatment with leonurine not
      only prevented cartilage destruction and subchondral bone thickening, but also
      alleviated synovitis in a murine OA model. Taken together, these results suggest
      that leonurine may be a potential therapeutic agent in OA treatment.

PMID- 30273918
TI  - Centralization and directional preference: An updated systematic review with
      synthesis of previous evidence.
AB  - BACKGROUND: Centralization and directional preference are common management and
      prognostic factors in spinal symptoms. OBJECTIVE: To update the previous
      systematic review. DESIGN: Systematic review to synthesis multiple aspects of
      centralization and directional preference. METHOD: Contemporary search was made
      of multiple databases using relevant search terms. Abstracts and titles were
      filtered by two authors; relevant articles were independently reviewed by two
      authors for content, data extraction, and quality. RESULTS: Forty-three
      additional relevant articles were found. The quality of the studies, using PEDro
      for randomized controlled trials, was moderate or high in six out of ten RCTs;
      moderate or high in six out of 12 cohort studies. Prevalence of centralization
      was 40%, the same as the previous review. Directional preference without
      Centralization was 26%; thus Centralization and directional preference combined
      was 66%, which was very similar to the previous review. Neither clinical response
      was recorded in about a third of patients. Centralization and directional
      preference were confirmed as key positive prognostic factors, certainly in
      patients with low back pain, but limited evidence for patients with neck pain.
      There was no evidence that these might be important treatment effect modifiers.
      One study evaluated reliability, and found generally poor levels, despite
      training. CONCLUSIONS: Centralization and directional preference are worthwhile
      indicators of prognosis, and should be routinely examined for even in patients
      with chronic low back pain. But they do not occur in all patients with spinal
      problems, and there was no evidence that they were treatment effect modifiers.

PMID- 30273919
TI  - Muscle fiber conduction velocity of the vastus medilais and lateralis muscle
      after eccentric exercise induced-muscle damage.
AB  - Change in muscle fiber conduction velocity (MFCV) has been reported after
      eccentric exercise induces muscle fiber damage, most likely due to a change in
      membrane permeability of the injured fiber. The extent of damage to the muscle
      fiber depends on the morphological and architectural characteristics of the
      muscle fibers. Morphological and architectural characteristics of the VMO muscle
      fibers are different from VL muscle. Thus, it is expected that eccentric exercise
      of quadriceps muscle results in a non-uniform fiber damage within the VMO and VL
      muscle and, as a consequence, non-uniform changes in membrane excitability and
      conduction velocity. The aim of the study was to investigate MFCV of the VMO and
      VL muscles before and 24 h after eccentric exercise. Multichannel surface EMG
      signals were concurrently recorded from the right VMO and VL muscles of 15
      healthy men during sustained isometric contractions at 50% of the maximal force.
      Maximal voluntary force significantly reduced after eccentric exercise with
      respect to the pre-exercise condition (P < 0.0001). MFCV decreased over time
      during the sustained contractions at faster rates when assessed 24 h after
      exercise (VMO = -26.1; VL = -20.1) with respect to the pre-exercise condition
      (VMO = -9.1; VL = -13.7, P < 0.0001). Moreover, VMO showed a greater rate of
      reduction in MFCV over sustained contraction (26.1 +/- 10.7%) in comparison with
      VL muscle (20.1 +/- 8.5%, P < 0.025) 24 h after eccentric exercise. The result
      indicates that eccentric exercise contributes to a larger reduction in MFCV
      within the VMO muscle as compared to the VL muscle. This may abolish the ability
      of VMO to counteract the lateral pull of the VL muscle during knee extension,
      thereby leaving the knee complex more vulnerable to injury.

PMID- 30273920
TI  - Application of MR-derived cross-sectional guideline of cervical spine muscles to
      validate neck surface electromyography placement.
AB  - The importance of surface-EMG placement for development and interpretation of EMG
      assisted biomechanical models is well established. Since MR has become a reliable
      noninvasive cervical spine musculoskeletal diagnostic tool, this investigation
      attempted to illustrate the anatomical relationships of individual cervical spine
      muscles with their paired surface-EMG electrodes. The secondary purpose of this
      investigation was to provide an MR cross-sectional pictorial and descriptive
      guideline of the cervical spine musculature. MR scans were performed on a healthy
      adult male subject from skull to manubrium of the sternum. Prior to scanning, MR
      safe markers were placed over neck muscles following surface EMG placement
      recommendations. Twenty-three neck muscles were traced manually in each of 267
      scan slices. 3-D models of the neck musculoskeletal structure were constructed to
      aid with understanding the complex anatomy of the region as well as to identify
      correct EMG electrode locations and to identify muscles' curved lines-of-action.
      3D models of the MR-safe markers were constructed relative to the target muscles.
      Based on the findings of this study, muscle palpation and bony landmarks can be
      used to effectively identify appropriate surface EMG electrode locations to
      record upper trapezius, middle trapezius, semispinalis capitis, splenius capitis,
      levator scapulae, scalenus, sternocleidomastoid and hyoid muscles activities.

PMID- 30273921
TI  - Under-dosing of drug due to inaccurate syringe markings: Vigilance and Quality
      control-the need of the hour.

PMID- 30273923
TI  - Left cerebral hemisphere hydrophilic polymer embolism associated with
      endovascular WEB treatment of a ruptured aneurysm of the anterior cerebral
      artery.
AB  - Hydrophilic polymer embolism (HPE) is a rare, likely under-recognized iatrogenic
      complication, caused by fragmentation of surface materials used on endovascular
      medical devices. The organs most often involved in HPE are the brain and lungs,
      resulting in both local and systemic reactions. We present the case of a cerebral
      HPE associated with WEB treatment of a ruptured aneurysm of the anterior cerebral
      artery, and involving diffusely the left cerebral hemisphere. The patient
      developed pneumonia and status epilepticus, and died 24 days after the
      endovascular procedure, most likely as a result of the sequelae of the aneurysm
      rupture. The precise role of HPE in the sequence of events leading to death can
      remain, as in this case, a matter for speculation. However, the potential role of
      HPE in the events leading to death following diagnostic and therapeutic
      procedures should be appropriately assessed, especially when recovery does not
      progress as expected.

PMID- 30273922
TI  - Quadriceps-strengthening exercise and quadriceps and knee biomechanics during
      walking in knee osteoarthritis: A two-centre randomized controlled trial.
AB  - OBJECTIVE: To assess the effect of quadriceps strengthening on quadriceps muscle
      force, power, and work and tibio-femoral compressive loads during walking in
      adults with knee osteoarthritis. METHODS: Study design: Two-center, randomized,
      controlled trial. INTERVENTION: Patients with knee osteoarthritis were randomly
      allocated to quadriceps strengthening program (3 times weekly) or no attention
      control group. MAIN OUTCOME MEASURES: Primary outcome was change from baseline in
      peak quadriceps force during walking at 12 weeks. Secondary outcomes included
      quadriceps power and work, knee compression forces during walking estimated with
      musculoskeletal modeling, muscle strength and pain and function. Outcomes were
      measured at baseline and 12 weeks. RESULTS: 30 patients were randomized to
      receive either training (n = 15) or no attention (n = 15). At follow-up, there
      were no statistical differences between groups for maximum quadriceps force,
      quadriceps positive power, negative work, and positive work, and knee compressive
      force. Maximum negative quadriceps power in early stance was statistically
      significantly increased 36% in the training group compared to the control group
      which was most likely partially a response to faster walking velocity at follow
      up. Muscle strength and patient reported pain and function were improved in the
      training group compared to the control group. CONCLUSIONS: Quadriceps strength
      training leads to increased muscle strength and improved symptomatic and
      functional outcomes but does not change quadriceps or knee joint biomechanics
      during walking. The biomechanical mechanism of improved health with strength
      training in knee osteoarthritis patients remains unknown. ClinicalTrials.gov
      Identifier: NCT01538407.

PMID- 30273925
TI  - Editorial overview: Cell signalling and gene regulation: Something new, something
      old, something borrowed, something blue.

PMID- 30273924
TI  - Recency of migration, region of origin and women's experience of maternity care
      in England: Evidence from a large cross-sectional survey.
AB  - BACKGROUND: In the UK, changes to legislation in 2003 regarding the free movement
      of people in the European Union resulted in an increase in immigration from
      countries that joined the EU since 2004, the Accession countries. OBJECTIVE: To
      describe and compare the maternity experiences of recent migrant mothers to those
      who had been resident in the UK for longer, and to UK-born women, while taking
      into account their region of origin. DESIGN: Cross-sectional national survey.
      SETTING: England, 2009. PARTICIPANTS: Random sample of postpartum women.
      MEASUREMENTS: Questionnaires asked about demographic characteristics, care during
      pregnancy, labour, birth and postnatally, about country of origin and, if not
      born in the UK, when they came to the UK. Country of origin was grouped into UK,
      Accession countries, and rest of the world. Recency of migration was grouped into
      recent arrivals (0-3 years), and earlier arrivals (4 or more years since
      arrival). Descriptive statistics and binary logistic regression were used to
      explore women's experiences of care. Stratified analyses were used to account for
      the strong correlation between recency of migration and region of origin.
      FINDINGS: Overall, 5332 women responded to the survey (a usable response rate of
      54%). Seventy-nine percent of women were UK-born. Of the 21% born outside the UK,
      a third were born in Accession countries. All migrants reported a poorer
      experience of care than UK-born women. In particular, recent migrants from the
      Accession countries were significantly less likely to feel that they were spoken
      to so they could understand and treated with kindness and respect. CONCLUSIONS:
      Given the rising population of non-UK-born women of childbearing age resident in
      the UK and the relatively high proportion from Accession countries, it is
      important that staff are able to communicate effectively, through interpreters if
      necessary. IMPLICATIONS FOR PRACTICE: The differences in clinical practice
      between women's home countries and the UK should be discussed so that women's
      expectations of care are informed about the options available to them.

PMID- 30273926
TI  - Convergent regulation of PIFs and the E3 ligase COP1/SPA1 mediates thermosensory
      hypocotyl elongation by plant phytochromes.
AB  - The ability of plants to sense and integrate daily and seasonal changes in light
      and temperature and to adjust their growth and development accordingly, is
      critical to withstand severe weather oscillations in a year. While molecular
      mechanisms controlling light responses are relatively well established, those
      involved in the perception and response to temperature are just beginning to be
      understood. Phytochromes emerged as major temperature sensors; due to warmer
      temperatures accelerate the dark reversal reaction to the Pr inactive state.
      Downstream of phytochromes, the bHLH Phytochrome Interacting Factors, and in
      particular PIF4, act as central signaling hubs to growth coordination in response
      to light and temperature cues, and to the gibberellin and brassinosteroid
      pathways. Here we discuss recent findings showing that phytochromes control PIFs
      activity not only by signaling their destruction in the light, but by modulating
      transcriptional repression of these factors by the circadian clock. Together with
      this repression, phytochromes inactivate the COP1/SPA ubiquitin ligase, which
      negatively regulates light signaling through degradation of a large set of
      nuclear photomorphogenesis-promoting factors that suppress PIFs activity.

PMID- 30273927
TI  - Oxygen Regulation in Development: Lessons from Embryogenesis towards Tissue
      Engineering.
AB  - Oxygen is a vital source of energy necessary to sustain and complete embryonic
      development. Not only is oxygen the driving force for many cellular functions and
      metabolism, but it is also involved in regulating stem cell fate, morphogenesis,
      and organogenesis. Low oxygen levels are the naturally preferred microenvironment
      for most processes during early development and mainly drive proliferation. Later
      on, more oxygen and also nutrients are needed for organogenesis and
      morphogenesis. Therefore, it is critical to maintain oxygen levels within a
      narrow range as required during development. Modulating oxygen tensions is
      performed via oxygen homeostasis mainly through the function of hypoxia-inducible
      factors. Through the function of these factors, oxygen levels are sensed and
      regulated in different tissues, starting from their embryonic state to adult
      development. To be able to mimic this process in a tissue engineering setting, it
      is important to understand the role and levels of oxygen in each developmental
      stage, from embryonic stem cell differentiation to organogenesis and
      morphogenesis. Taking lessons from native tissue microenvironments, researchers
      have explored approaches to control oxygen tensions such as hemoglobin-based,
      perfluorocarbon-based, and oxygen-generating biomaterials, within synthetic
      tissue engineering scaffolds and organoids, with the aim of overcoming
      insufficient or nonuniform oxygen levels and nutrient supply.

PMID- 30273928
TI  - KU70 Inhibition Impairs Both Non-Homologous End Joining and Homologous
      Recombination DNA Damage Repair Through SHP-1 Induced Dephosphorylation of SIRT1
      in Adult T-Cell Leukemia-Lymphoma Cells.
AB  - BACKGROUND/AIMS: Adult T-cell leukemia-lymphoma (ATL) is an aggressive disease
      which is highly resistant to chemotherapy. Studies show that enhanced ability of
      DNA damage repair (DDR) in cancer cells plays a key role in chemotherapy
      resistance. Here, we suggest that defect in DDR related genes might be a
      promising target to destroy the genome stability of tumor cells. METHODS: Since
      KU70 is highly expressed in Jurkat cells, one of the most representative cell
      lines of ATL, we knocked down KU70 by shRNA and analyzed the impact of KU70
      deficiency in Jurkat cells as well as in NOD-SCID animal models by western blot,
      immunofluorescence, flow cytometry and measuring DNA repair efficiency. RESULTS:
      It is observed that silencing of KU70 resulted in accumulated DNA damage and
      impaired DDR in Jurkat cells, resulting in more apoptosis, decreased cell
      proliferation and cell cycle arrest. DNA damage leads to DNA double-strand breaks
      (DSBs), which are processed by either non-homologous end joining(NHEJ) or
      homologous recombination(HR). In our study, both NHEJ and HR are impaired because
      of KU70 defect, accompanied with increased protein level of SHP-1, a
      dephosphorylation enzyme. In turn, SHP-1 led to dephosphorylation of SIRT1, which
      further impaired HR repair efficiency. Moreover, KU70 deficiency prolonged
      survival of Jurkat-xenografted mice. CONCLUSION: These findings suggest that
      targeting KU70 is a promising target for ATL and might overcome the existing
      difficulties in chemotherapy.

PMID- 30273929
TI  - Unbalanced 14;X Translocation and Pattern of X Inactivation in a Female Patient
      with Multiple Congenital Anomalies.
AB  - We report on a female patient who was first evaluated at the age of 6 years with
      developmental delay, dysmorphic facial features, seizures, and autistic behavior.
      A brain CT showed complete agenesis of the corpus callosum, and EEG recorded
      bilateral epileptogenic foci. Karyotype analysis revealed 45,X,psu
      dic(14;X)(p11;p22). FISH using 14q and Xp subtelomeric probes, combined with a
      SHOX gene-specific probe, and centromere X and XIST gene analysis revealed ish
      psu dic(14;X)(D14S1420+; DXYS129-, SHOX-, DXZ1+, XIST+). Array CGH detected a 2
      Mb loss at Xp22.33 and a 4.6-Mb gain at Xp22.2p22.12. The deletion contains 34
      genes, of which CSF2RA and SHOX are OMIM morbid genes. The duplication also
      contains some OMIM morbid genes, of which CDKL5, NH5, RPS6KA3, and AP1S2 are the
      most important. The late replicating chromatin technique was used to detect the
      pattern of X inactivation in the normal X and in the translocated chromosome. The
      translocated X was found to be inactive in 70% of the studied blood lymphocytes
      with patchy extension of inactivation to chromosome 14. In conclusion, the
      phenotype of the patient may be partially affected by the haploinsufficiency of
      the genes that are known to escape X inactivation and that lie within the deleted
      region and by other deleted or duplicated genes on the abnormal X chromosome due
      to an alternative pattern of X inactivation. The phenotype of the patient was
      significantly aggravated and complicated by the functional monosomy of some genes
      on chromosome 14 due to partial spreading of inactivation and silencing of those
      genes. This case report indicates the importance of structural and functional
      studies and emphasizes the clinical importance of the follow-up of abnormal
      microarrays.

PMID- 30273930
TI  - Reply to the Letter by Singer, Mitter, and Porsch Related to Our Paper "Benefits
      of Individualized Feedback in Internet-Based Interventions for Depression: A
      Randomized Controlled Trial".

PMID- 30273931
TI  - Inflammation in Diabetic Kidney Disease.
AB  - BACKGROUND: Diabetes is a growing public health problem. Diabetic kidney disease
      (DKD) is the most prevalent chronic renal disease and the major cause of end
      stage renal failure worldwide, predominantly due to the increase of Type 2
      diabetes associated with obesity. The intimate mechanisms leading to the
      development and progression of renal injury in DKD are not well understood, but
      current knowledge indicates that its pathogenesis is multifactorial, where the
      immune response and inflammation appear to be relevant factors. SUMMARY: This
      review summarizes the role of relevant inflammatory molecules and pathways that
      participate in the development of DKD. Likewise, we focused on the new
      therapeutic approaches based on anti-inflammatory effects of different drugs. Key
      Messages: This new pathogenic perspective of DKD as an inflammatory condition
      leads to novel horizons, such as the potential role of inflammatory signaling
      pathways and their downstream products as emerging biomarkers and promising
      therapeutic targets.

PMID- 30273932
TI  - Relationship of Autophagy and Apoptosis with Total Occlusion of Coronary
      Arteries.
AB  - BACKGROUND The primary aim of this study was to evaluate the level of autophagy
      and apoptosis enzymes in patients with coronary artery disease (CAD).
      Furthermore, we investigated the role of autophagy and apoptosis in the
      progression of coronary collateral and coronary total occlusion (TO). MATERIAL
      AND METHODS We enrolled 115 patients in this prospective, observational,
      controlled study, who were categorized into 3 groups as follows: group 1,
      patients with chronic TO (n=49); group 2, patients with acute TO such as
      myocardial infarction (n=36); and group 3, healthy control patients (n=30). We
      used the enzyme-linked immunosorbent assay (ELISA) kit for autophagy-related
      protein 5 (ATG5) and apoptosis (M30) in the plasma for these 3 groups. RESULTS
      Autophagy levels significantly varied among the groups (13.7+/-5.3 ng/mL, 11.7+/
      3.4 ng/mL, and 7.5+/-3, respectively; P<0.001). In addition, apoptosis levels
      significantly varied among the groups (78.6+/-33.4 ng/mL, 64.9+/-30.6 ng/mL, and
      47.6+/-18.2, respectively; P<0.001). The subgroup analysis revealed significant
      positive correlations between the autophagy level and the Rentrop score in
      contrast to apoptosis in group 1 (r=0.463; P<0.001). CONCLUSIONS This study
      determined that autophagy and apoptosis levels were higher in patients with CAD
      than in healthy controls. In contrast to the serum apoptosis level, serum
      autophagy levels demonstrated a significant positive correlation with the Rentrop
      score. Hence, an elevated autophagy level might be a potential activator and
      marker of the process by which the body protects itself in CAD.

PMID- 30273934
TI  - Noninvasive Liver Fibrosis Tests in Patients with Nonalcoholic Fatty Liver
      Disease: An External Validation Cohort.
AB  - The main aim of this study was the comparative evaluation of nonalcoholic fatty
      liver disease (NAFLD) fibrosis score (NFS), fibrosis 4 index (FIB-4), AST-to
      Platelet Ratio Index (APRI), and enhanced liver fibrosis (ELF) test in
      distinguishing none/early (F0/F1) from significant/advanced (F2/F3) fibrosis in
      NAFLD patients, thereby providing an external validation cohort. Thirty-one
      patients with biopsy-proven NAFLD and 10 matched controls without NAFLD were
      prospectively enrolled. Serum hyaluronic acid (HA), aminoterminal propeptide of
      type III procollagen (PIIINP), tissue inhibitor of metallo-proteinases (TIMP)-1,
      and biochemical tests were measured. NFS, FIB-4, APRI, and ELF were calculated.
      ELF, FIB-4, and APRI, but not NFS, were higher in F2/F3 than F0/F1 group.
      Specifically, ELF [area under the ROC curve (AUROC): 0.86+/-0.10; p=0.004) and
      APRI (AUROC: 0.86+/-0.07; p=0.005], but not NFS (AUROC: 0.68+/-0.12; p=0.16), and
      FIB-4 (AUROC: 0.71+/-0.11; p=0.10), could similarly discriminate F0/F1 from F2/F3
      stage. The sensitivity, specificity, positive predicted value (PPV), and negative
      predicted value (NPV) were: a) for cut-off of APRI=0.5, 85.7%, 70.8%, 46.2%, and
      94.4%, respectively, and b) for cut-off of ELF=9.0, 85.7%, 83.3%, 60.0%, and
      95.2%, respectively. When ln(PIIINP) or TIMP-1 were combined with APRI, the
      combined AUROCs could distinguish F2/F3 from F0/F1, but without significantly
      higher accuracy compared with APRI alone. APRI could also distinguish patients
      with simple steatosis from nonalcoholic steatohepatitis, and those with from
      those without lobular inflammation and ballooning, findings warranting further
      research. In conclusions: The application of ELF test and APRI can distinguish
      F0/F1 from F2/F3 fibrosis stages in NAFLD patients.

PMID- 30273935
TI  - The 3PAs: An Update on the Association of Pheochromocytomas, Paragangliomas, and
      Pituitary Tumors.
AB  - Pituitary adenomas (PA) and pheochromocytomas/paragangliomas (PHEO/PGL) are rare
      tumors. Although they may co-exist by coincidence, there is mounting evidence
      that genes predisposing in PHEO/PGL development, may play a role in pituitary
      tumorigenesis. In 2012, we described a GH-secreting PA caused by an SDHD mutation
      in a patient with familial PGLs and found loss of heterozygosity at the SDHD
      locus in the pituitary tumor, along with increased hypoxia-inducible factor
      1alpha (HIF-1alpha) levels. Additional patients with PAs and SDHx defects have
      since been reported. Overall, prevalence of SDHx mutations in PA is very rare
      (0.3-1.8% in unselected cases) but we and others have identified several cases of
      PAs with PHEOs/PGLs, like our original report, a condition which we termed the 3
      P association (3PAs). Interestingly, when 3PAs is found in the sporadic setting,
      no SDHx defects were identified, whereas in familial PGLs, SDHx mutations were
      identified in 62.5-75% of the reported cases. Hence, pituitary surveillance is
      recommended among patients with SDHx defects. It is possible that the SDHx
      germline mutation-negative 3PAs cases may be due to another gene, epigenetic
      changes, mutations in modifier genes, mosaicism, somatic mutations, pituitary
      hyperplasia due to ectopic hypothalamic hormone secretion or a coincidence. PA in
      3PAs are mainly macroadenomas, more aggressive, more resistant to somatostatin
      analogues, and often require surgery. Using the Sdhb +/- mouse model, we showed
      that hyperplasia may be the first abnormality in tumorigenesis as initial
      response to pseudohypoxia. We also propose surveillance and follow-up approach of
      patients presenting with this association.

PMID- 30273933
TI  - The heart in systemic lupus erythematosus - A comprehensive approach by
      cardiovascular magnetic resonance tomography.
AB  - BACKGROUND: In systemic lupus erythematosus (SLE), cardiac manifestations, e.g.
      coronary artery disease (CAD) and myocarditis are leading causes of morbidity and
      mortality. The prevalence of subclinical heart disease in SLE is unknown. We
      studied whether a comprehensive cardiovascular magnetic resonance (CMR) protocol
      may be useful for early diagnosis of heart disease in SLE patients without known
      CAD. METHODS: In this prospective, observational, cross-sectional study CMR
      including cine, late gadolinium enhancement (LGE) and stress perfusion sequences,
      ECG, and blood sampling were performed in 30 consecutive SLE patients without
      known CAD. All patients fulfilled at least 4/11 American College of Rheumatology
      (ACR) Criteria for the classification of SLE. RESULTS: 30 patients (83% female)
      were enrolled, mean age was 45+/-14 years and mean SLE disease duration was 10+/
      8 years. 80% had low to moderate disease activity. All had a low SLE damage
      index. CMR was abnormal in 13/30 (43%), showing LGE in 9/13, stress perfusion
      deficits in 5/13 and pericardial effusion (PE) in 7/13. Patients with non
      ischemic LGE had more often microalbuminuria while patients with stress perfusion
      deficits a history of hypertension, renal disorder as ACR criterion,
      repolarisation abnormalities on ECG and larger LV enddiastolic volume index.
      There was no correlation between clinical symptoms and CMR results. CONCLUSION:
      Our study shows that cardiac involvement as observed by CMR is frequent in SLE
      and not necessarily associated with typical symptoms. CMR may thus help to detect
      subclinical cardiac involvement, which could lead to earlier treatment.
      Additionally we identify possible risk factors associated with cardiac
      involvement.

PMID- 30273937
TI  - [Utilization of Gynaecological Cancer Screening by Women 20 to 35 Years of Age
      Receiving Unemployment Benefits Under Social Security Code II].
AB  - The aim of the study was to analyze associations between utilization of
      gynaecological cancer screening (GCS) and the number of months during which state
      unemployment benefits (Social Security Code II) were drawn by women aged 20 to 35
      years. The sample included 223 women with complete interview data (participation
      rate: 69%). The findings show that more women drawing unemployment benefits for a
      short-term (<12 months) utilized GCS compared to those receiving long-term
      benefits (>36 months).

PMID- 30273936
TI  - [Influence of Parental Body Measurements on Birth Weight of Eutrophic Term
      Newborns with Special Consideration of Paternal Body Measurements].
AB  - A significant influence of maternal body height and weight on neonatal birth
      outcome has been confirmed before, whereas the influence of paternal traits is
      rather unknown. In order to analyze the correlation between parental body
      measurements and the birth weight of newborns, data of 1312 eutrophic term
      newborns and their parents were collected based on a multicenter study in 10
      participating German maternity clinics. The collected data included the birth
      weight of the infants and the body height and weight of their parents. The
      results show a significant correlation between infant birth weight and maternal
      body height. Even with a constant body height and body weight of fathers in a
      range between 176-184 cm and 76-84 kg, taller mothers gave birth to children with
      a higher birth weight than shorter mothers. Furthermore, higher maternal body
      weight is also correlated with increased birth weights, although this correlation
      is attenuated in higher maternal weight groups. Data regarding body weight and
      body height of fathers showed similar results with regard to birth weight of the
      newborns. At a constant maternal body height (164-172 cm) and weight (56-64 kg),
      the body weight of newborns significantly correlates with the body height of
      fathers but not with their body weight. The multivariable regression analysis
      resulted in the following ranking of influence factors on the birth weight of
      newborns: 1) body height of mother, 2) body weight of mother, 3) body height of
      father. The results gave support to the assumption of a certain genetic influence
      of parental body stature on their neonates but argue for an even stronger impact
      of maternal environmental conditions on the developmental status of neonates.

PMID- 30273938
TI  - [Obstacles in Secondary Analysis of Routine Data From Primary Care].
AB  - BACKGROUND: Routinely recorded data from everyday ambulatory medical care are
      urgently needed for health services and systems research, but this faces major
      limitations in Germany. In 2018, European General Data Protection Regulation
      (GDPR) and new German Federal Data Protection Act (FDPA) become effective. Via
      simulated real-life scenarios it may be possible to find out if access to and
      utilization of routine data for research becomes easier or faces additional
      obstacles. METHODS: General practitioners, information scientists, data trustees
      and privacy protection experts create concepts, processes and standards for
      lawful handling of routinely recorded data for secondary research and study their
      feasibility in 2 scenarios (anonymous and pseudonymous data utilization). From
      the point of view of technical assessment and privacy protection, technical and
      organizational obstacles are presented as well as the legal framework. RESULTS:
      Outdated software interface, insufficient maintenance by software vendors,
      burdens associated with organization and cost as well as poor IT standards place
      obstacles to systematic and longitudinal use of healthcare routine data. Future
      pan-European law for privacy protection will allow research utilization of
      ambulatory data in principle. However, there are persisting conflicts between
      individual (fundamental right of privacy protection) and public interests
      (research for quality and efficiency of public spending; European market's free
      exchange of goods and services). This becomes evident especially when using
      routine data via pseudonymization. DISCUSSION: Neither insurmountable hurdles by
      privacy protecting law nor a threat from Big Data are currently the major
      obstacles to secondary utilization of routine data but real-life problems at the
      technology and operational level. GDPR and FDPA that have become into effect in
      May 2018 have improved European legal unity and transparency of patients'
      interests. Tension between privacy protection of data on an identified or
      identifiable person and scientific utilization and exchange of such data in
      public interest necessitates additional legal clarification. One possible
      solution, an advanced and ready-to-use software interface, awaits implementation.

PMID- 30273939
TI  - [Future of Regional Health Care in Germany: Where Do Young Dentists Want to
      Work?]
AB  - STUDY AIM: In the context of a shortfall in medical care, the question arises
      whether a similar trend in dental care may be anticipated. This study analyses
      preferred working regions and future town-country distribution of young dentists
      in Germany. METHODS: This online-survey was conducted in spring 2017. It is the
      second wave of the longitudinal nationwide study "Y-dent: Professional identity
      of future and young dentists". Study end points were (1) favoured permanent
      working region of young dentists, (2) favoured future working city size, and (3)
      correlation between the region of origin and the favoured working region.
      RESULTS: 625 (51.2% of contacted) young dentists participated in this study.
      Dental chambers and associations of health insurance dentists in southern and
      western Germany were the most favoured future working regions. Regions in eastern
      Germany as well as smaller regions were chosen less often (<10%). For
      approximately half of the participants, medium-sized cities were an option, and
      some young dentists were ready to work in smaller cities. Depending on the
      federal state, 57-95% of young dentists entertained the idea of working in their
      region of origin. CONCLUSION: Based on young dentists' statements on their
      favoured future working region, it can be concluded that there is no risk of a
      shortfall in dental care comparable to the shortfall in medical care. A
      proportion of young dentists is willing to work in thinly populated or rural
      areas.

PMID- 30273940
TI  - Community-based Mental Healthcare: A Case Study in a Cross-border Region of
      Germany and the Netherlands.
AB  - BACKGROUND: Community-based mental healthcare (CBMH) aims at supplying
      psychiatric patients with rehabilitative care outside the hospital. The aim of
      this study was to compare the organization of CBMH in a cross-border region of
      Germany and the Netherlands. METHOD: Semi-structured interviews gave insight into
      characteristics of CBMH approaches applied in the German region of Aachen (IHP)
      and the Dutch Province of Limburg (FACT). We applied a Delphi technique to select
      a performance indicator (PI) set for CBMH, which served as a conceptual model to
      allow comparison. RESULTS: Both approaches are flexible, patient-centred and
      include the evaluation of quality. Both provide financial and administrative
      support for the access. CONCLUSION: CBMH approaches appear to be equally valid
      from several perspectives even if they revealed, at the same time, important
      differences related to scope, integration with non-CBMH care resources and
      geographic coverage. Secondarily, the study provides a contribution to the
      development of a PI set to compare and evaluate CBMH approaches.

PMID- 30273941
TI  - [Preventive Home Visits for Elderly People: A Systematic Appraisal of Current
      Application in Germany].
AB  - OBJECTIVE: Preventive home visits (PHV) are a measure for promoting the health of
      elderly people. A study of these measures used over the past 40 years in many
      countries across the globe revealed a very diverse picture regarding targeted
      groups, applied structures and intervention contents. So far, there has been no
      clear evidence of their effectiveness on outcomes such as mortality, need for
      care, hospital or nursing home admissions. However, a steady increase in PHV
      programmes in Germany warrants an examination of the current national practice.
      MATERIAL/METHODS: PHV programmes in Germany were identified in the course of
      Internet-based research (January 2018) and systematically compared by means of
      nine criteria that were defined beforehand. RESULTS: 38 PHV programmes were
      included: 26 currently implemented, and 12 that have been terminated. These
      showed a considerable variety in terms of their programme components. Medicine
      oriented and social environment-oriented programmes (n=8 vs. n=24) could be
      differentiated. Relevant differentiation criteria were sponsorship, profession of
      home visitors and intervention contents. Thus, the practice in Germany is
      characterised as follows: municipal sponsorship, social workers conducting home
      visits, and guidance by consulting services disregarding integrated case
      management. Programmes of this type mainly emerged only in the current decade.
      CONCLUSIONS: PHV for elderly people evolved from initially medicine-oriented into
      rather social environment-oriented programmes of municipal public service. They
      target elderly people with unclear need for support who, at the same time, are
      confronted with barriers to accessing suitable services. The anticipated main
      effect of PHV relates to the safeguarding of social participation. However,
      evidence for their effectiveness, still pending, should be made available before
      a broad or even legally anchored application is envisaged.

PMID- 30273942
TI  - [National Action Plan Health Literacy: Need, Objective and Content].
AB  - In recent years, studies on health literacy of the population have been conducted
      in many countries. Most of them show that health literacy levels are worse than
      expected and that large parts of the population have low health literacy levels.
      National strategies and action plans to promote health literacy have been
      developed in many countries to address these results. Following these examples, a
      National Action Plan on Health Literacy was also developed for Germany. A panel
      of 15 experts was involved in the 2-year development process. Based on an
      analysis of available literature on health literacy and existing action plans,
      the concept, objectives and priorities of the action plan were defined, and
      recommendations were developed. The National Action Plan on Health Literacy
      formulates recommendations in the fields of living environments, the healthcare
      system, chronic illness, and research.

PMID- 30273943
TI  - Simultaneous F18-FDG-PET/MR Optimized Treatment Planning in a Young Patient with
      Sacro-Coccygeal Chordoma.

PMID- 30273945
TI  - [Current challenges in the treatment of paediatric burn patients: a retrospective
      experience at a Viennese burn unit].
AB  - BACKGROUND: Burn trauma in paediatric patients continues to be highly relevant
      socio-economically since the number of inpatients treated per year has not
      declined over the past few decades. The treatment of paediatric burn victims
      places high demands on medical staff and the use of wound dressings and surgical
      techniques. This study aimed to give a current overview of the inpatient
      management and treatment methods for paediatric burn patients at a specialised
      burn centre in Vienna. PATIENTS/MATERIAL AND METHODS: All children and
      adolescents who were treated at the children's ward of the Division of Plastic
      and Reconstructive Surgery at the Medical University of Vienna between 2012 and
      2016 due to a recent burn trauma were retrospectively analysed. RESULTS:
      115patients were treated due to a recent burn trauma. Median age was 2 years (0
      18). Scalds accounted for 74 % of traumas. Median affected body surface area was
      5 % (1-40 %). Conservative treatment of superficial partial-thickness wounds (62
      %) was performed with MepilexAg in 98 % of cases and required a median healing
      time of 11 days (4-34). 38 % (n = 44) of patients had deep partial-thickness or
      full-thickness burns . The use of Suprathel after tangential excision of the burn
      eschar in more superficial deep partial-thickness burns led to satisfying healing
      times. CONCLUSION: The use of modern dressings in the conservative treatment of
      superficial partial-thickness burns allows for atraumatic dressing changes and
      fast recoveries. The use of Suprathel in more superficial deep partial-thickness
      burns is a reliable and safe alternative to autologous skin grafting. Scar
      prophylaxis and regular follow-up examinations are crucial to prevent secondary
      morbidity due to scar contractures. It is important to raise awareness among
      parents in order to decrease the number of paediatric burn patients in the
      future.

PMID- 30273944
TI  - [Plastic-reconstructive treatment options for burns caused by concrete exposure].
AB  - BACKGROUND: In industry as well as in the private sector, cement is often used as
      building material. Although severe skin injuries are known to be caused due to
      improper handling of cement, the incidence and severity of these cutaneous
      injuries are often underestimated. Heavy cement burns are rare but in our centers
      the authors treat affected patients on a regular basis. The aim of this study is
      to analyze the given patient data in order to give treatment suggestions.
      PATIENTS AND METHODS: During 2013 to 2017, a total of 7 patients (median age: 39
      years), which had suffered chemical burns after concrete, cement or screed
      exposure, were treated in two German plastic-surgical clinics. The authors
      performed a retrospective data analysis by using the hospital information systems
      (HIS). RESULTS: All patients were treated with surgical interventions. Median
      inpatient treatment period was 9.8 days (n = 6). The average time for surgery was
      1:04 hours (n = 5). During surgical treatment an average of 1.4 operations were
      performed (n = 7). In all cases a sustained wound healing could be achieved.
      CONCLUSIONS: If a patient suffers from a concrete burn, a fast and competent
      initial treatment is imperative in order to prevent worse. The presented patient
      cases prove the value of these rare but devastating medical conditions.
      Therefore, it is essential to implement the given treatment recommendations for a
      sustainable patient care.

PMID- 30273946
TI  - Antidiabetic Potentials of Citrus aurantifolia Leaf Essential Oil.
AB  - Citrus aurantifolia leaf essential oil was extracted via hydrodistillation,
      chemical composition of the oil was analyzed using gas chromatography-mass
      spectrometry and its antidiabetic potentials was assessed in alloxan-induced
      hyperglycaemic rats using metformin as the reference drug for comparison.
      Chemical analysis showed that D-limonene (57.84%) was the major constituent of
      the oil. Other notable compounds identified were neral (7.81%), linalool (4.75%),
      sulcatone (3.48%) and isogeraniol (3.48%). Intraperitoneal administration of C.
      aurantifolia oil (100 mg/Kg b.wt.) to hyperglycaemic rats for 14 days caused
      significant reduction in fasting blood and hepatic glucose, whereas hepatic
      concentration of glycogen was significantly increased. Also, improvement in
      dyslipidaemia was observed in C. aurantifolia essential oil-treated
      hyperglycaemic rats; serum concentration of total cholesterol, triacylglycerol
      and low density lipoprotein-cholesterol were significantly reduced and high
      density lipoprotein-cholesterol was increased, resulting in decreased
      predisposition of rats to cardiac risks. Antihyperglycaemic potential of
      administration of the oil was lower but compared favourably with the oral
      antihyperglycaemic agent used as reference antidiabetic drug. Overall, data from
      this study showed that essential oil from the leaf of C. aurantifolia grown in
      North-Central Nigeria is a D-limonene chemotype. The oil showed considerable
      glucose lowering effect as well as the potential to ameliorate hyperglycaemia
      induced dyslipidaemic complications in alloxanized rats.

PMID- 30273947
TI  - [Stroke Patients After Inpatient Neurological Rehabilitation - A Prospective
      Study to Determine Predictors of Survival at Home up to Five Years After
      Discharge].
AB  - PURPOSE: To identify factors influencing the long-term survival at home in stroke
      patients after neurological inpatient rehabilitation. METHODS: The study was
      conducted as a prospective cohort study in 204 stroke patients who were treated
      in the course of one year in the Herzogenaurach Rehabilitation Hospital
      (rehabilitation phases C and B). The social data and clinical data were collected
      during inpatient rehabilitation. The outcome variable was assessed up to 5 years
      after discharge. Differences between groups were analysed with t-tests or chi
      square tests. Binary logistic regression analyses were carried out for
      multivariate predictor analyses. RESULTS: The regression analysis resulted in a
      prediction model consisting of 5 variables for living at home 2.5 years after
      discharge (vs. institutionalization or death): a greater increase in health
      related quality of life during inpatient rehabilitation, better health-relate
      quality of life at discharge, a greater increase in functional independence
      during inpatient rehabilitation, a higher body-mass index and fewer comorbidity
      conditions associated with a mortality risk. 5 years after discharge the
      prediction model consists of 3 variables: lower age, fewer comorbidity conditions
      associated with a mortality risk and lower risk for falls at discharge from
      neurological rehabilitation. CONCLUSION: Up to 2.5 years after discharge the
      extent of functional improvement and the improvement of health related quality of
      life, which are both correlated with therapeutic effects, are predictors for
      survival and living at home. On the other hand, 5 years after discharge
      biological factors as age and comorbidities are prognostically dominating.

PMID- 30273948
TI  - [Quality of German-Language Guidelines for Post-Stroke Rehabilitation of Aphasia
      and Dysarthria - Results of a Systematic Review and of an International
      Comparison].
AB  - AIM: Evaluation of German-language guidelines for aphasia and dysarthria
      rehabilitation, and comparison with international guidelines. METHODS: The
      quality of the 6 included guidelines, as found through a comprehensive literature
      search, was sytematically evaluated using AGREE II. Quality ratings were compared
      to the results of a systematic review of 19 English-language guidelines. RESULTS:
      The quality of German-language guidelines was heterogeneous. In 2 out of 6
      evaluation domains and in the overall assessment, no German-language guideline
      reached the cut-off of 66,67% for good guideline quality. Apart from the domain
      Editorial Independence, results remained behind those of the international
      reference guidelines. CONCLUSION: In some cases, quality can be improved by
      simple means. It is more resource-intensive, but crucial to document search
      strategies and how evidence was used in guideline development. A harmonization of
      the German-language guidelines seems desirable.

PMID- 30273949
TI  - [Usability of Input Devices and Aids in the Field of Augmentative and Alternative
      Communication - An Experimental Study with People with and without Disabilities].
AB  - This study explored the usability of 15 different assistive input devices for
      persons with severe motor disabilities. Fifteen people without disabilities were
      asked to speak a predefined test-sentence and then to write it using 15 different
      input aids. Ten persons with severe motor and communication disabilities wrote
      the same sentence using their own communication aid. The usability was evaluated
      in 3 dimensions: efficiency (speed as information transfer rate in bit per
      second), effectiveness (proportion of correct input over all input including
      errors and error correction), and user's satisfaction with an adapted version of
      the Quest II questionnaire. Participants without disabilities needed 40 to 140
      times more time to write the sentence using the aid compared to speech,
      participants with disability between 13 to 500 times. The effectiveness was
      between 80  and 100% for the participants without disabilities and between 73 and
      100% for the participants with disabilities. Satisfaction was between 3.4 and 5.0
      (max.) for the participants without disability and between 2.8 and 5.0 for the
      participants with disabilities. Overall the input by standard devices such as
      keyboard and mouse had better usability than the more complex devices like eye
      gazing technology. Comparable types of control (head control, eye control) also
      had similar usability. The usability dimensions of efficiency, effectiveness and
      satisfaction with input aids as examined in this study could be evaluated in the
      process of recommending communication and writing aids. The focus should however
      not only be on the input aids as such, but also include all optimization options
      such as word prediction and auto text.

PMID- 30273950
TI  - Stellera chamaejasme and Its Main Compound Luteolin 7-O-Glucoside Alleviates Skin
      Lesions in Oxazolone- and 2,4-Dinitrochlorobenzene-Stimulated Murine Models of
      Atopic Dermatitis.
AB  - Stellera chamaejasme, also known as "Langdu", has been traditionally used for the
      management of skin-related diseases such as psoriasis and skin ulcers. The aim of
      this study was to determine whether S. chamaejasme and its major component,
      luteolin 7-O-glucoside, have a preventive effect on the development of atopic
      dermatitis in oxazolone-treated BALB/c mice and 2,4-dinitrochlorobenzene-treated
      hairless mice. The epicutaneous applications of oxazolone and 2,4
      dinitrochlorobenzene evoke an experimental murine atopic dermatitis-like reaction
      in BALB/c mouse ears and SKH-1 hairless mice. Atopic skin symptoms, including
      erythema (redness), pruritus (itching), exudation (weeping), excoriation
      (peeling), and lichenification (skin thickening), responded to treatment with S.
      chamaejasme aerial parts EtOH extract for 2 or 3 weeks. Histopathological
      examination revealed S. chamaejasme aerial parts EtOH extract significantly
      reduced inflammatory cell infiltration when applied to atopic dermatitis mice. In
      addition, luteolin 7-O-glucoside, the major active compound of the S. chamaejasme
      aerial parts EtOH extract, decreased serum IgE and IL-4 levels and transepidermal
      water loss and increased skin hydration, therefore exhibiting strong anti-atopic
      dermatitis activity in 2,4-dinitrochlorobenzene-induced atopic dermatitis mice.
      In this study, we confirmed antipruritic and antidermatitic effects of S.
      chamaejasme extract and its main component luteolin 7-O-glucoside in atopic
      dermatitis murine models. The study shows S. chamaejasme aerial parts EtOH
      extract and luteolin 7-O-glucoside are most likely to be potential drug
      candidates for atopic dermatitis treatment.

PMID- 30273951
TI  - Platelet Function Testing after Transcatheter Aortic Valve Implantation.

PMID- 30273952
TI  - Searching for High-Risk Venous Thromboembolism Patients Using Risk Scores: Adding
      to the Heap or Closing a Gap?

PMID- 30273953
TI  - Heparanase and Thrombin: Common Signalling Pathways in Melanoma Cells?

PMID- 30273954
TI  - Long-Term Outcome after Joint Bleeds in Von Willebrand Disease Compared to
      Haemophilia A: A Post Hoc Analysis.
AB  - Long-term outcome after joint bleeds in von Willebrand disease (VWD) (von
      Willebrand factor activity <= 30 IU/dL) could differ from moderate or severe
      haemophilia A (HA) (factor VIII [FVIII] 1-5 IU/dL or FVIII < 1 IU/dL). We
      performed a post hoc analysis on Haemophilia Joint Health Score (HJHS, 0-124), X
      ray Pettersson scores (PS, 0-13/joint) and the Haemophilia Activities List (HAL,
      0-100), using multivariable regression to adjust for age (rate ratio [RR] or odds
      ratio [OR] [95% confidence interval]). We included 48 VWD (median age, 47 years,
      type 3 VWD, n = 19), 39 moderate HA (median, 39 years) and 59 severe HA patients
      (median, 25 years) with documented joint bleeds. VWD patients suffered repeated
      bleeding (lifetime > 5/joint) less often than moderate and severe HA patients
      (52% vs. 77% vs. 98%). HJHS and PS in VWD were similar to moderate HA (median
      HJHS 5 vs. 6, RR 0.9 [0.5-1.4] and PS > 3 of >= 1 joint OR 0.3 [0.1-1.4]), but
      better than in severe HA patients (median HJHS 5 vs. 9, RR 1.8 [1.1-2.9]; PS > 3
      in any joint OR 0.1 [0.0-0.3]). Self-reported limitations in activities were
      comparable across VWD, moderate HA (HAL score < 95: 67% vs. 49%; OR 1.4 [0.5
      3.6]) and young adults with severe HA (67% vs. 48%; OR 1.7 [0.7-4.4]). Despite
      fewer joint bleeds, joint outcome after joint bleeds was similar in VWD and
      moderate HA patients. Type 3 VWD patients had worst joint outcome, comparable to
      younger intensively treated severe HA patients. Limitations in activities
      occurred as often in VWD as in both moderate and severe HA.

PMID- 30273955
TI  - Evaluation of human observer performance on lesion detectability in single-slice
      and multislice dedicated breast cone beam CT images with breast anatomical
      background.
AB  - PURPOSE: We evaluate the lesion detectability using human and model observer
      studies in single-slice and multislice cone beam computed tomography (CBCT)
      images with a breast anatomical background. The purposes of this work are (a) to
      compare human observer detectability between single-slice and multislice images
      for different signal sizes and noise structures, (b) to investigate the effect of
      different multislice viewing modes (i.e., sequential and simultaneous) on the
      detectability by a human observer, and (c) to predict the detectability by a
      human observer in single-slice and multislice images using single-slice
      channelized Hotelling observer (ssCHO) and multislice CHO (msCHO), respectively.
      METHODS: Breast anatomical background is modeled using a power law spectrum of
      mammograms and the lesion is modeled with a spherical signal. We conduct signal
      known-exactly and background-known-statistically detection tasks on transverse
      and longitudinal images reconstructed using the Feldkamp-Davis-Kress algorithm
      with Hanning and Ram-Lak weighted ramp filters. The human observer study is
      conducted on three different viewing modes: single-slice, and sequential and
      simultaneous multislice. To predict the detectability by a human observer, we use
      ssCHO and msCHO with anthropomorphic channels (i.e., dense difference-of-Gaussian
      (D-DOG) and Gabor channels) and internal noise. RESULTS: The detectability by a
      human observer increases for multislice images compared to single-slice images.
      For multislice images, the sequential viewing mode yields higher detectability
      than the simultaneous viewing mode. However, the relative rank of detectability
      by a human observer for different signal sizes, image planes, and reconstruction
      filters is not much different between the viewing modes. Detectability by CHO
      with internal noise shows good correlation with that of the human observer for
      all viewing modes. CONCLUSIONS: Detectability by a human observer in CBCT images
      with breast anatomical background is affected by the image viewing mode, and the
      effect of the viewing mode depends on the signal size and noise structure. D-DOG
      and Gabor CHO with internal noise predict the detectability by a human observer
      well for both the single-slice and multislice image viewing modes.

PMID- 30273956
TI  - Interwealth Contact and Young Children's Concern for Equity.
AB  - This study examined young children's contact with individuals of high-wealth and
      low-wealth backgrounds and their behavior toward peers of these backgrounds in a
      resource distribution task. The sample included 72 ethnically diverse higher
      income children (Mage  = 6.68 years, SD = 0.98 years). Contact with individuals
      of low-wealth backgrounds (interwealth contact) affected children's behavior
      indirectly, through social-cognitive reasoning processes. The more interwealth
      contact children reported, the more likely they were to reason about access to
      resources rather than their own wealth preferences in this context. This
      reasoning, in turn, was associated with more resources allocated to a low-wealth
      peer relative to a high-wealth peer. Thus, interwealth contact early in
      development was associated with more equitable peer interactions.

PMID- 30273957
TI  - High-precision noise power spectrum measurements in digital radiography imaging.
AB  - PURPOSE: Accurately and precisely estimating the noise power spectrum (NPS) is
      important for characterizing the performance of a radiography detector and
      helpful for improving the performance when developing radiography detectors. In
      order to produce an accurate estimate, the frequency resolution should be
      sufficiently high, and for a precise estimate, the sample size for the sample
      mean should also be large enough. However, there is a trade-off between the
      frequency resolution and the sample size if the available samples are limited. To
      improve the precision of the estimate, a radial averaging technique is employed
      in the IEC standard without sacrificing the frequency resolution or the estimate
      accuracy. In the radial averaging technique, directional NPS curves of a range
      are averaged from the two-dimensional NPS, and thus, directional error and poor
      precision problems occur, especially at low frequencies. This problem also leads
      to uncertainties in calculating the detective quantum efficiency (DQE).
      Therefore, the purpose of this study is to develop algorithms that can improve
      the precisions in estimating NPS to replace the radial averaging technique or to
      add additional precision. METHODS: The horizontal or vertical NPS curve can be
      estimated using the sample mean of the summation of directional cross
      periodograms with various distances from the two-dimensional NPS. In practical x
      ray imaging, the amplitude response of the cross periodograms decreases rapidly
      as the distance increases. Hence, a partial summation of the cross periodograms
      can provide an accurate estimate of the NPS. This partial summation can increase
      the sample size and thus improve the estimate precision for the entire frequency
      range without causing directional errors. This paper proposes two estimate
      algorithms under the notion of the partial use of cross periodograms. RESULTS: In
      order to evaluate the precisions from the proposed algorithms, a relative
      precision, which is defined as the standard deviation of the estimate divided by
      its average, was employed. The relative precisions were calculated using 100 x
      ray images acquired from a general radiography detector. For the detector, we
      were able to achieve a better precision compared to using the radial averaging
      technique. For an image of 900 * 900 pixels and the region of interest size 256
      in a direction with a half overlap, the conventional approach of the IEC standard
      yielded an average relative precision of 6.96% with the worst precision of 36.1%
      at the zero frequency. However, the proposed algorithms could yield an average
      relative precision of 4.14% with the zero-frequency precision of 5.79%.
      CONCLUSIONS: Without using the radial averaging technique, the proposed
      algorithms in this paper could improve the estimate precisions for the entire
      frequency range under the notion of a partial summation of the cross
      periodograms. Especially for low frequencies including the zero frequency, the
      proposed algorithms could achieve a high-precision to estimate the NPS.

PMID- 30273958
TI  - Self-rated health, symptoms and health behaviour of upper secondary vocational
      students by field of study.
AB  - This article examines the self-rated health, symptoms and health behaviour of
      upper secondary vocational students in Finland. The data consist of the responses
      of first- and second-year vocational students (n = 34 554) to the 2013 School
      Health Promotion Survey. The data were analysed statistically and processed
      separately for girls and boys. Associations between self-rated health, symptoms
      and health behaviour and fields of study were examined by cross-tabulation.
      Statistical significance was measured using the chi-squared test. Self-rated
      health, symptoms and health behaviour were found to have a statistically
      significant association with field of study (p < 0.001). Vocational students in
      different fields had different experiences of health, different symptoms and
      different health behaviours. The results complement existing evidence about
      disparities in well-being among young people in the context of education.

PMID- 30273959
TI  - Hemodynamic Evaluation of Avalon Elite Bi-Caval Dual Lumen Cannulas and Femoral
      Arterial Cannulas.
AB  - Translational research is a useful tool to provide scientific evidence for
      cannula selection during extracorporeal life support (ECLS). The objective of
      this study was to evaluate four Avalon Elite bi-caval dual lumen cannulas and
      nine femoral arterial cannulas in terms of flow range, circuit pressure, pressure
      drop, and hemodynamic energy transmission in a simulated adult ECLS model. A veno
      venous ECLS circuit was used to evaluate four Avalon Elite bi-caval dual lumen
      cannulas (20, 23, 27, and 31 Fr), and a veno-arterial ECLS circuit was used to
      evaluate nine femoral arterial cannulas (15, 17, 19, 21, and 23 Fr). The two
      circuits included a Rotaflow centrifugal pump, a Quadrox-D adult oxygenator, and
      3/8 in ID tubing for arterial and venous lines. The circuits were primed with
      lactated Ringer's solution and packed human red blood cells (hematocrit 40%).
      Trials were conducted at rotational speeds from 1000 to 5000 RPM (250 rpm
      increments) for each Avalon cannula, and at different flow rates (0.5-7 L/min)
      for each femoral arterial cannula. Real-time pressure and flow data were recorded
      for analysis. Small caliber cannulas created higher circuit pressures, higher
      pressure drops and higher M-numbers compared with large ones. The inflow side of
      Avalon dual lumen cannula had a significantly higher pressure drop than the
      outflow side (inflow vs. outflow: 20 Fr-100.2 vs. 49.2 mm Hg at 1.1 L/min, 23 Fr
      93.7 vs. 41.4 mm Hg at 1.6 L/min, 27 Fr-102.3 vs. 42.8 mm Hg at 2.6 L/min, 31 Fr
      98.1 vs. 44.7 mm Hg at 3.8 L/min). There was more hemodynamic energy lost in the
      veno-arterial ECLS circuit using small cannulas compared to larger ones (17 Fr
      vs. 19 Fr vs. 21 Fr at 4 L/min-Medtronic: 71.0 vs. 64.8 vs. 60.9%; Maquet: 71.4
      vs. 65.6 vs. 62.0%). Medtronic femoral arterial cannulas had lower pressure drops
      (Medtronic vs. Maquet at 4 L/min: 17 Fr-121.7 vs. 125.0 mm Hg, 19 Fr-71.2 vs.
      73.7 mm Hg, 21 Fr-42.9 vs. 47.4 mm Hg) and hemodynamic energy losses (Medtronic
      vs. Maquet at 4 L/min: 17 Fr-43.6 vs. 44.4%, 19 Fr-31.0 vs. 31.4%, 21 Fr-20.8 vs.
      22.4%) at high flow rates when compared with the Maquet cannulae. The results for
      this study provided valuable hemodynamic characteristics of all evaluated adult
      cannulas with human blood in order to guide ECLS cannula selection in clinical
      practice. Use of larger cannulas are suggested for VV- and VA-ECLS.

PMID- 30273960
TI  - Novel mutation in Teneurin 3 found to co-segregate in all affecteds in a multi
      generation family with developmental dysplasia of the hip.
AB  - DDH is a debilitating condition characterized by incomplete formation of the
      acetabulum leading to dislocation of the hip, suboptimal joint function and
      accelerated wear of the articular cartilage resulting in early onset crippling
      arthritis of the hip in 20-40 year olds. Current diagnostic tests in newborns
      using physical manipulation of the femur or ultrasound either under or over
      diagnose this condition. Developing an accurate, cost effective diagnostic test
      is a goal of this study. To better understand the biologic pathways involved in
      acetabular development, DNA from severely affected individuals in a four
      generation family that showed inter-generational transmission of the disorder was
      isolated and whole exome sequenced. A novel A to C transversion at position
      183721398 on human chromosome four was found to co-segregate with the affected
      phenotype in this family. This mutation encodes a glutamine to proline change at
      position 2665 in the Teneurin 3 (TENM3) gene and was judged damaging by four
      prediction programs. Eight week old knock-in mutant mice show delayed development
      of the left acetabulum and the left glenoid fossa as shown by the presence of
      more Alcian blue staining on the socket rims of both the hip and the shoulder. We
      hypothesize that mutated TENM3 will slow chondrogenesis. MMP13 has been shown to
      impair extracellular matrix remodeling and suppress differentiation. Bone marrow
      cells from the knock-in mouse were found to overexpress MMP13 with or without
      BMP2 stimulation. This variant may elucidate pathways responsible for normal hip
      development and become part of an accurate test for DDH. (c) 2018 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

PMID- 30273961
TI  - Improvement in colistin-induced reproductive damage, apoptosis, and autophagy in
      testes via reducing oxidative stress by chrysin.
AB  - This study aimed to investigate the effect of chrysin on colistin-induced
      reproductive toxicity. Twenty-eight adult male Sprague-Dawley rats were divided
      into four groups of seven rats each. Group I received physiological saline for 7
      days. Group II received 50 mg/kg/day chrysin for 7 days. Group III received a
      total dose of 73 mg/kg colistin for 7 days. Group IV received 50 mg/kg/day
      chrysin by an oral gavage after the colistin treatment. Colistin causes an
      increase in oxidative stress (OS) in the testis. Chrysin treatment significantly
      decreased the OS in the chrysin + colistin group compared with the colistin
      group. The highest caspase-3 and LC3B expression levels were found in the
      colistin group and these levels were statistically lower in the chrysin +
      colistin group. Colistin treatment caused a decrease in sperm motility and an
      increase in sperm abnormality. Chrysin treatment mitigated these side effects
      significantly. In conclusion, chrysin treatment can be beneficial against
      colistin-induced reproductive toxicity.

PMID- 30273962
TI  - p-Hydroxybenzyl alcohol inhibits four obesity-related enzymes in vitro.
AB  - Recently, antiobesity studies using the method of inhibiting enzymatic activity
      of obesity-related enzymes as targets have received considerable attention. The
      aims of the current study were to investigate whether p-hydroxybenzyl alcohol
      (HBA), identified from Cudrania tricuspidata fruits with antiobesity effects,
      inhibits the activity of digestive and obesity-related enzymes and acts as an
      inhibitor against four target enzymes in kinetic studies. In vitro enzyme assays
      showed HBA at the highest concentration significantly reduced the enzymatic
      activity of four targets: pancreatic lipase (IC50  = 2.34-3.70 MUM), alpha
      glycosidase (IC50  = 9.08 MUM), phosphodiesterase IV (IC50  = 4.99 MUM), and
      citrate synthase (IC50  = 2.07 MUM) enzymes. Based on the results of kinetic
      assays, the types of inhibition were investigated. Our findings indicate that HBA
      could have antiobesity efficacy, and it deserves further study.

PMID- 30273963
TI  - A circular echo planar sequence for fast volumetric fMRI.
AB  - PURPOSE: To demonstrate a circular EPI (CEPI) sequence as well as a generalized
      EPI reconstruction for fast fMRI with parallel imaging acceleration. METHODS: The
      CEPI acquisition was constructed using variable readout lengths and maximum ramp
      sampling as well as blipped-CAIPI z-gradient encoding for simultaneous multislice
      (SMS) and 3D volumetric imaging. A signal equation model with constant and linear
      phase terms was used to iteratively reconstruct images with low ghosting.
      Simulation, phantom, and human imaging experiments including audio/visual fMRI
      were performed at 3T using a 52-channel coil. RESULTS: Application of CEPI
      gradients with duration of 27 ms covering a 22-cm FOV at a 64 * 64 pixel
      resolution in SMS and 3D acquisitions resulted in images with comparable quality
      to those of standard Cartesian EPI. With parallel imaging techniques robust
      detection of BOLD fMRI activation with temporal sampling down to 275 ms was
      possible. The high temporal resolution enabled higher activation statistics at a
      penalty in increased noise and residual aliasing. The un-accelerated 3D
      acquisition showed large temporal instability compared with a standard 2D
      acquisition. CONCLUSION: Nonuniform sampling and generalized image
      reconstructions can be applied to EPI acquisitions including those with blipped
      CAIPI z gradients. The same gradients can be used for either SMS or 3D
      acquisitions providing identical coverage.

PMID- 30273964
TI  - Oligomeric proanthocyanidins mitigate cholesterol and cholic acid diet-induced
      hepatic dysfunction in male Sprague Dawley rats.
AB  - Dysregulated synthesis of hepatic cholesterol is a critical determinant of
      atherosclerosis. The combination of cholesterol and cholic acid (CC) diet
      supplementation to animal models is associated with hepatic dysfunction-mediated
      atherosclerosis. The current study was designed to investigate the hepatic
      cholesterol-lowering effects of oligomeric proanthocyanidins (OPC) in CC diet fed
      rats. CC diet-induced group exhibited significant increase in the hepatic lipid
      profile, activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      (HMGR), PON-1, LCAT, LPL, and LPO levels, and messenger RNA expression of HMGR,
      low-density lipoprotein receptor (LDLr), and HNF-4alpha. Administration of OPC
      (100 mg/kg/bwt) resulted in the significant reduction of lipid profile and HMGR
      levels, with concomitant increase in the levels of cholesterol-regulating enzymes
      and upregulated expression of LDLr and HNF-4alpha, which was similar to
      atorvastatin. Molecular docking studies also revealed that proanthocyanidins had
      a strong binding affinity to HMGR, similar to atorvastatin. Our findings suggest
      that OPC regulate the impaired cholesterol metabolism-associated atherosclerosis
      through hepatic cholesterol-lowering effect.

PMID- 30273965
TI  - A predictive algorithm for spot position corrections after fast energy switching
      in proton pencil beam scanning.
AB  - PURPOSE: Fast energy switching is of fundamental importance to implement motion
      mitigation techniques in pencil beam scanning proton therapy, allowing efficient
      irradiation and high patient throughput. However, depending on magnet design,
      when switching between different energy layers, eddy currents arise in the
      bending magnets' yoke, damping the speed of the magnetic field change and
      lengthening the settling time of the magnetic field. In a proton therapy gantry,
      this can cause a temporary displacement of the beam trajectory and consequently
      an incorrect beam position in the bending direction, resulting in an unacceptable
      loss of position precision at isocenter. The precision can be recovered by either
      increasing the beam off time after an energy change (waiting until the magnetic
      field is fully settled) or by actively correcting for the misplacement. We
      studied the transient magnetic field effects at PSI Gantry 2 in order to develop
      a correction strategy for this beam position misplacement. METHODS: We used
      position and proton range sensitive detectors (segmented strip chamber and
      multilayer ionization chambers respectively) to measure the difference between
      expected and actual proton beam position and range as a function of time. The
      detectors are automatically triggered, read out, and analyzed by the treatment
      control system. We studied the effects due to the magnets on the gantry and those
      upstream of the gantry separately, in order to identify which elements contribute
      the most to the beam position instability. We then designed a spot position
      algorithm to be applied with the gantry scanning magnets, to correct for the
      displacement observed as a function of time and achieve the PSI Gantry 2 clinical
      target of 1 mm precision at isocenter at all times, even after an energy change.
      RESULTS: When switching energy layers in a field, we observed an exponentially
      decaying spot position displacement at isocenter. The effect increases with
      increasing energy difference between energy layers (DeltaE). The initial
      residuals between expected and measured position are higher than 1 mm for most of
      the clinical cases at Gantry 2 and fall below 1 mm within about 1 s or more
      (depending on DeltaE). We found no time dependence for the proton range, thus
      confirming that the displacement is purely due to a beam trajectory displacement
      resulting from the longer settling time of the magnetic field. A double
      exponential model, with two time constants and amplitudes depending on DeltaE,
      fits the data and provides an easy model for the correction function. We
      implemented this correction as a spot position correction, applied by the
      scanning magnets during field application. After correction, the residuals were
      below 0.5 mm right after the energy change. CONCLUSIONS: We developed a spot
      position correction for PSI Gantry 2 which reduces the beam off time needed in
      current state-of-the-art gantries to settle the magnetic fields in the bending
      magnets. Thanks to this correction, the spot position is stable within 100 ms of
      an energy change at Gantry 2. This is low enough to make possible efficient use
      of motion mitigation techniques.

PMID- 30273967
TI  - A cost-effectiveness threshold based on the marginal returns of cardiovascular
      hospital spending.
AB  - Traditionally, threshold levels of cost-effectiveness have been derived from
      willingness-to-pay studies, indicating the consumption value of health (v
      thresholds). However, it has been argued that v-thresholds need to be
      supplemented by so-called k-thresholds, which are based on the marginal returns
      to health care. The objective of this research is to estimate a k-threshold based
      on the marginal returns to cardiovascular disease (CVD) hospital care in the
      Netherlands. To estimate a k-threshold for hospital care on CVD, we proceed in
      two steps: First, we estimate the impact of hospital spending on mortality using
      a Bayesian regression modelling framework, using data on CVD mortality and CVD
      hospital spending by age and gender for the period 1994-2010. Second, we use life
      tables in combination with quality of life data to convert these estimates into a
      k-threshold expressed in euros per quality-adjusted life year gained. Our base
      case estimate resulted in an estimate of 41,000 per quality-adjusted life year
      gained. In our sensitivity analyses, we illustrated how the incorporation of
      prior evidence into the estimation pushes estimates downwards. We conclude that
      our base case estimate of the k-threshold may serve as a benchmark value for
      decision making in the Netherlands as well as for future research regarding k
      thresholds.

PMID- 30273966
TI  - Oncogenic HBXIP enhances ZEB1 through Sp1 to accelerate breast cancer growth.
AB  - BACKGROUND: There is abundant evidence to indicate that HBXIP functions as an
      oncoprotein and transcription co-activator during the development and promotion
      of cancers. In multiple cancers, ZEB1 serves as a transcription activator to
      regulate gene expression. We explored the roles of ZEB1 in HBXIP-induced breast
      cancer growth. METHODS: HBXIP regulation of ZEB1 was evaluated by reverse
      transcription PCR and immunoblotting. The stimulation of ZEB1 promoter by HBXIP
      and/or Sp1 was tested using luciferase reporter gene analysis. The alteration of
      cell proliferation mediated by HBXIP-induced ZEB1 was tested using methyl
      thiazolyl-tetrazolium and 5-Ethynyl-2'-deoxyuridine (EdU) incorporation analysis.
      ZEB1 and HBXIP expression in human breast cancer tissues was analyzed using
      quantitative real-time PCR. The relationship between HBXIP and ZEB1 was confirmed
      by Pearson's correlation coefficient. RESULTS: We observed dose-dependent
      upregulation of ZEB1 by HBXIP in breast cancer cells. HBXIP can activate the ZEB1
      promoter by interacting with transcription factor Sp1. Cell viability and EdU
      incorporation analysis showed that HBXIP could drive cell proliferation by
      enhancing ZEB1 in breast cancer. Using quantitative real-time PCR, ZEB1
      overexpression and a positive relationship between ZEB1 and HBXIP were observed
      in clinical breast cancer samples. CONCLUSION: Oncogenic HBXIP controls the
      transcription regulation of ZEB1 by co-activating Sp1, thereby accelerating
      breast cancer growth.

PMID- 30273968
TI  - Translation of morphological and functional musculoskeletal imaging.
AB  - In an effort to develop quantitative biomarkers for degenerative joint disease
      and fill the void that exists for diagnosing, monitoring, and assessing the
      extent of whole joint degeneration, the past decade has been marked by a greatly
      increased role of noninvasive imaging. This coupled with recent advances in image
      processing and deep learning opens new possibilities for promising quantitative
      techniques. The clinical translation of quantitative imaging was previously
      hampered by tedious non-scalable and subjective image analysis. Osteoarthritis
      (OA) diagnosis using X-rays can be automated by the use of deep learning models
      and pilot studies showed feasibility of using similar techniques to reliably
      segment multiple musculoskeletal tissues and detect and stage the severity of
      morphological abnormalities in magnetic resonance imaging (MRI). Automation and
      more advanced feature extraction techniques have applications on larger more
      heterogeneous samples. Analyses based on voxel based relaxometry have shown local
      patterns in relaxation time elevations and local correlations with outcome
      variables. Bone cartilage interactions are also enhanced by the analysis of three
      dimensional bone morphology and the potential for the assessment of metabolic
      activity with simultaneous Positron Emission Tomography (PET)/MR systems. Novel
      techniques in image processing and deep learning are augmenting imaging to be a
      source of quantitative and reliable data and new multidimensional analytics allow
      us to exploit the interactions of data from various sources. In this review, we
      aim to summarize recent advances in quantitative imaging, the application of
      image processing and deep learning techniques to study knee and hip OA. (c)2018
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
      XX:XX-XX, 2018.

PMID- 30273969
TI  - Becoming more or less mature? The decline of self-control in middle childhood.
AB  - OBJECTIVE: This study examined the developmental change in self-control and its
      association with daily stressful events during middle childhood, as well as the
      factors that contribute to individual differences in the trajectory of self
      control. METHOD: A community sample of 302 Singaporean children (42% female, 69%
      Chinese) and their parents were recruited when the children were age 7. Follow-up
      assessments were made when the children were ages 8, 9, and 11. Developmental
      changes were examined using latent growth and autoregressive cross-lagged models.
      RESULTS: Self-control showed a normative decline over time, and this trajectory
      was associated with an increase in daily stressful events. There was partial
      evidence for a reciprocal relationship between self-control and daily stressful
      events over time. Moreover, the child temperament dimension of effortful control
      (assessed at age 7) mitigated the decline in self-control, whereas low
      socioeconomic status predicted lower initial levels of self-control. CONCLUSIONS:
      This study advances current understanding on the developmental change in self
      control during middle childhood, as well as the factors that shape the direction
      and magnitude of this change.

PMID- 30273970
TI  - Age at referral for diagnosis and rehabilitation services for cerebral palsy: a
      scoping review.
AB  - AIM: This study sought to: (1) determine what is known about age at referral for
      diagnosis and rehabilitation services for children suspected of having cerebral
      palsy (CP); and (2) identify factors associated with earlier referral. METHOD: A
      scoping review was conducted to summarize existing literature. We systematically
      searched Allied and Complementary Medicine, CINAHL, Cochrane Library, Embase, and
      PsycINFO for evidence published between 1979 and 2017 on age at referral for
      diagnosis or age at referral to rehabilitation services for children suspected of
      having CP. Quantitative and thematic analyses of the literature were performed.
      RESULTS: Our search yielded 777 articles, of which 15 met the inclusion criteria.
      Only one study focused on age at referral for diagnosis of CP (mean 16.6mo+/
      19.2mo), with two on age at referral to rehabilitation services (means 13.9mo+/
      15.8mo and 12.4mo). Potential predictors of earlier referral identified include
      referral source, type of CP, and a complicated birth history. INTERPRETATION:
      Evidence is sparse; however, available studies suggest high variation in the age
      at which children are being referred for diagnosis, typically ranging from 10
      months to 21 months. Evidence indicates that subgroups of children with CP might
      be experiencing prolonged delays. Findings highlight the need to better
      understand what contributes to delays in referral for diagnosis and
      rehabilitation. WHAT THIS PAPER ADDS: Evidence on age at referral for diagnosis
      of cerebral palsy is sparse. Potential predictors of delayed referral represent
      targets to minimize delays in diagnosis. A subset of children may be experiencing
      unnecessary delays in referral.

PMID- 30273971
TI  - Agmatine protects against sodium valproate-induced hepatic injury in mice via
      modulation of nuclear factor-kappaB/inducible nitric oxide synthetase pathway.
AB  - Valproate is a widely used drug against epilepsy and several other neurological
      disorders although it has deleterious hepatotoxic side effects. The current study
      was designed to test if agmatine as nitric oxide modulator has protective effects
      against valproate-induced hepatic injury. Male Swiss albino mice were treated
      with sodium valproate (SVP) with or without agmatine for 7 days. Serum and liver
      samples were collected for analysis. Results have revealed that agmatine exerted
      hepatoprotective effects against SVP-associated hepatic injury. Agmatine
      ameliorated SVP-induced elevated serum biochemical markers of hepatic damage such
      as serum transaminases, alkaline phosphatase, gamma-glutamyl transferase, and
      lactate dehydrogenase. Histopathological examination of the liver showed
      improvement of hepatic lesions in case of agmatine treatment. Furthermore,
      agmatine attenuated oxidative stress and enhanced antioxidants in liver tissue.
      Agmatine inhibited the activation of nuclear factor-kappaB and ameliorated the
      immunoexpression of inducible nitric oxide synthetase. This was accompanied by
      decrease in the level of inflammatory markers as nitrite/nitrate, tumor necrosis
      factor-alpha, and interleukin-6. These data provide new evidence of the
      hepatoprotective activity of agmatine against SVP-induced hepatotoxic effects.

PMID- 30273972
TI  - Antibacterial activities of plasma from the common (Chelydra serpentina) and
      alligator snapping turtle (Macrochelys temminckii).
AB  - Innate immunity provides a fast-acting and nonspecific defense against microbial
      infection, and appears to have particular importance in the immune response of
      ectothermic vertebrates. Chelonians are a globally distributed and diverse group,
      yet little is known about their basic immune function. The chelonian family
      Chelydridae is made up of two genera (Chelydra and Macrochelys), represented in
      our study by the widespread common snapping turtle ( Chelydra serpentina; CST)
      and the southeast USA endemic alligator snapping turtle ( Macrochelys temminckii;
      AST). Our goal was to quantify the innate immune response of the family
      Chelydridae, using the antibacterial activity of plasma as a measure of immune
      function. Our results show that the plasma of both species has strong
      antibacterial properties, but CST plasma kills a higher percentage of bacteria
      than AST plasma. In addition, while both species showed the highest antibacterial
      activity at 25 to 30 degrees C, CST plasma retained its antibacterial properties
      at lower and higher temperatures than AST plasma. Our results indicate that, like
      many ectotherms, Chelydridae have a relatively strong innate immune response. The
      stronger, more robust immune response of CSTs compared with ASTs is likely
      correlated to the differences in geographic ranges but may also have implications
      for each species' tolerance to anthropogenic habitat degradation and global
      climate change.

PMID- 30273973
TI  - Follicular development of canine ovaries stimulated by a combination treatment of
      eCG and hCG.
AB  - Ovarian follicular dynamics is not well known in dogs. Imaging of ovaries is
      technically difficult; however, ovaries clamped at a subcutaneous site can more
      easily be monitored using ultrasound imaging. This study investigated the
      follicular development of canine ovaries stimulated by hormone treatment using
      ultrasound imaging of the ovaries clamped at a subcutaneous site. Oestrus was
      induced using subcutaneous administration of 500 IU equine chorionic gonadotropin
      (eCG) and 1000 IU human chorionic gonadotropin (hCG) (eCG/hCG). Five bitches were
      given 1000 IU hCG 11 days after eCG/hCG administration. Examinations with ovarian
      ultrasonography using a 7.5-MHz sector transducer, vaginal cytology, and assays
      of serum oestrogen and progesterone were performed daily until 20 days after
      eCG/hCG administration. Serosanguineous vaginal discharges and vaginal cytology
      of two of the bitches were observed. New follicular growth (>1.0 mm in diameter)
      was observed in all bitches from 2 to 8 days after eCG/hCG administration. The
      mean diameter of follicles and maximum numbers of follicles per ovary ranged from
      2.8 to 5.5 mm and 4 to 16, respectively. The elevation in oestrogen
      concentrations after eCG/hCG administration was observed in all bitches, and
      elevation in progesterone concentration (>2 ng mL-1 ) was observed in three
      bitches. However, no follicles ovulated until 9 days after hCG administration. In
      conclusion, although the number of examined bitches were limited, follicular
      growth in ovaries clamped at a subcutaneous site can be monitored using
      ultrasound imaging. Ovarian ultrasonography showed that eCG/hCG administration
      induced new follicular growth and hCG administration induced increases in
      oestrogen concentrations but not ovulation by hCG administration.

PMID- 30273974
TI  - Sleep Problems in Adults With Autism Spectrum Disorder and Intellectual
      Disability.
AB  - : Sleep problems (SP) are recognized as a common comorbid condition in autism
      spectrum disorder (ASD) and can influence core autism symptoms and mental and
      physical health. SPs can be lifelong and have been reported that adults on the
      autistic spectrum with and without intellectual disability (ID) present SPs
      (longer sleep latency, frequent night awakenings, and circadian rhythm sleep-wake
      disorders). A prospective, objective sleep study was conducted in 41 adults with
      ASD (33 +/- 6 years old) and ID and 51 typically developing adults (33 +/- 5
      years old) using ambulatory circadian monitoring (ACM) recording wrist
      temperature, motor activity, body position, sleep, and light intensity. The
      findings indicated that individuals with ASD presented sleep difficulties
      including low sleep efficiency, prolonged sleep latency and increased number and
      length of night awakenings, together with daily sedentary behavior, and increased
      nocturnal activity. Furthermore, indications of an advanced sleep-wake phase
      disorder were found in these autistic adults. Examining sleep and markers of the
      circadian system showed significant differences between adults with ASD and ID
      and an age-matched, healthy adult population. The sleep disturbances described
      for this sample of adults with ASD and ID are similar to those of already
      described for adults with ASD without ID; their relationship with intellectual
      ability should be further studied. Improving knowledge of sleep patterns in ASD
      adults with ID might help to designed targeted interventions to improve their
      functioning and reduce family stress. Autism Res 2018. (c) 2018 International
      Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: SPs are very
      frequent in autism from childhood to adulthood. We recorded sleep with a watch
      like device in adults with autism and ID and compared sleep patterns with
      nonautistic volunteers. Results showed poorer sleep conditions in adults with
      autism (increased sleep latency and number/length of night awakenings) that
      resulted in decreased sleep efficiency. Increasing knowledge of the SPs in adults
      on the autism spectrum will allow to improve their and their families' quality of
      life.

PMID- 30273975
TI  - Experimental study of needle recording electrodes placed on the thyroid cartilage
      for neuromonitoring during thyroid surgery.
AB  - BACKGROUND: Needle electrodes placed on the thyroid cartilage (TC) are an
      alternative to endotracheal tube (ET) electrodes for assessing recurrent
      laryngeal nerve (RLN) function during thyroid surgery. Needle electrodes placed
      on the TC were evaluated in an experimental porcine model. METHODS: Continuous
      intraoperative neuromonitoring was used to record the electromyogram. Each TC
      side was delineated into nine areas to determine the optimal placement of the
      electrode, and needle electrode area, depth and orientation for optimal
      electromyographic (EMG) amplitudes were evaluated. RLN root locations were
      stimulated at four locations: vagus nerve distal to the neuromonitoring
      electrode, and most proximal, middle and laryngeal entry points of the nerve. A
      nerve retraction injury model was adapted to compare RLN monitoring by TC versus
      ET electrodes. RESULTS: An optimal site for placement of needle electrodes was
      identified, and electromyograms obtained from the various needle insertion depths
      and orientations were similar. Latencies recorded from the TC and ET electrodes
      were similar. The amplitude profile of TC electrodes responded earlier to RLN
      injury than that of ET electrodes. Amplitude and drop to loss of signal were also
      registered earlier. CONCLUSION: EMG amplitudes obtained using TC electrodes were
      higher, and identified RLN injury earlier than ET electrodes. Surgical relevance
      Needle electrodes placed on the thyroid cartilage (TC) are an alternative to
      endotracheal tube (ET) electrodes for assessing the function of the recurrent
      laryngeal nerve (RLN) in thyroid surgery. This study used an experimental porcine
      model to evaluate the use of needle electrodes inserted in the TC, compared with
      ET electrodes, for producing an electromyographic (EMG) profile of the RLN. Nine
      areas of the TC, with various needle insertion depths and orientations, were
      compared. Perichondral insertion into the avascular area of the TC was found to
      be safe. The EMG amplitude and latency features recorded via the TC and ET
      electrodes were compared, using both intermittent and continuous monitoring.
      Changes in EMG amplitudes in response to nerve traction injury were registered
      earlier with TC electrodes than with ET electrodes, and the amplitudes were
      higher and more stable. Latencies obtained via the TC and ET electrodes were
      similar. These results indicate that the development of a non-invasive monitoring
      electrode with improved function, easy placement and low cost is possible.

PMID- 30273976
TI  - Physician characteristics, industry transfers, and pharmaceutical prescribing:
      Empirical evidence from medicare and the physician payment sunshine act.
AB  - OBJECTIVE: To evaluate physician characteristics associated with pharmaceutical
      industry transfers and prescribing behavior after public reporting under the
      Sunshine Act. DATA SOURCES: 2014-2016 secondary data on industry transfers to
      physicians from the Open Payments Dataset supplemented with Medicare Part D
      prescription data, Medicare service data, and practice attributes from the
      Physician Compare Database. STUDY DESIGN: Using regression analysis with
      county/physician fixed effects, this study examines characteristics associated
      with the probability/magnitude of transfers and the association between transfers
      and prescriptions. DATA COLLECTION: Using an iterative matching approach, this
      study identifies physicians who delivered outpatient Medicare services in 2014 (n
      = 409 041) and tracks their annual transfers between 2014 and 2016 (N = 1 227
      123) across six transfer categories. In addition, it examines their Medicare Part
      D prescription behavior between 2014 and 2015 (N = 741 659). PRINCIPAL FINDINGS:
      Industry transfers dramatically declined in 2015 and 2016. Transfers are
      significantly associated with increased prescription costs, branded prescribing,
      and prescribing for High-Risk Medications (HRMs). CONCLUSIONS: Industry transfers
      have declined after public reporting. Transfers are associated with higher
      prescription costs and incidence of HRMs. Future research is needed to determine
      the causal impact on quality and cost-effectiveness of prescribed medications.

PMID- 30273977
TI  - Preclinical induced membrane model to evaluate synthetic implants for healing
      critical bone defects without autograft.
AB  - Critical bone defects pose a formidable orthopaedic problem in patients with bone
      loss. We developed a preclinical model based on the induced membrane technique
      using a synthetic graft to replace autograft for healing critical bone defects.
      Additionally, we used a novel osteoconductive scaffold coupled with a synthetic
      membrane to evaluate the potential for single-stage bone regeneration. Three
      experimental conditions were investigated in critical femoral defects in rats.
      Group A underwent a two-stage procedure with insertion of a
      polymethylmethacrylate (PMMA) spacer followed by replacement with a 3D printed
      polycaprolactone(PCL)/beta-tricalcium phosphate (beta-TCP) osteoconductive
      scaffold after 4 weeks. Group B received a single-stage PCL/beta-TCP scaffold
      wrapped in a PCL-based microporous polymer film creating a synthetic membrane.
      Group C received a single-stage bare PCL/beta-TCP scaffold. All groups were
      examined by serial radiographs for callus formation. After 12 weeks, the femurs
      were explanted and analyzed with micro-CT and histology. Mean callus scores
      tended to be higher in Group A. Group A showed statistically significant greater
      bone formation on micro-CT compared with other groups, although bone volume
      fraction was similar between groups. Histology results suggested extensive bone
      ingrowth and new bone formation within the macroporous scaffolds in all groups
      and cell infiltration into the microporous synthetic membrane. This study
      supports the use of a critical size femoral defect in rats as a suitable model
      for investigating modifications to the induced membrane technique without
      autograft harvest. Future investigations should focus on bioactive synthetic
      membranes coupled with growth factors for single-stage bone healing. (c) 2018
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

PMID- 30273978
TI  - Weighty Conversations: Caregivers', Children's, and Clinicians' Perspectives and
      Experiences of Discussing Weight-Related Topics in Healthcare Consultations.
AB  - Children with autism spectrum disorder (ASD) are at a higher risk of having
      obesity than their typically developing peers. Although it has been recommended
      that health care providers (HCPs) speak to caregivers and children about the risk
      of higher weights, no research has examined how HCPs communicate weight-related
      information. Furthermore, there is a dearth of evidence regarding how to approach
      and deliver optimal weight-related discussions among children with ASD and their
      caregivers. Given these knowledge gaps, 21 in-depth interviews were conducted
      with children with ASD, their caregivers, and HCPs. Using a qualitative analytic
      approach, data from interviews were analyzed thematically. Results suggest that
      HCPs at times projected weight stigma during clinical encounters, which did not
      motivate children and caregivers to work toward work loss or wellness. HCPs also
      described reticence in engaging families in weight-related conversations due to
      limited training, and lack of clinical tools to guide these conversations. All
      stakeholders identified a need to work together to establish a therapeutic
      partnership to discuss weight-related issues without blame or shame. The
      combination of strength-based communication approaches, establishing a strong
      therapeutic partnership, and development of clinical tools facilitating weight
      related discussions for HCPs outlined in this article are potential vehicles to
      foster successful weight-related discussions while promoting lifelong wellness.
      Autism Research 2018, 11: 1500-1510. (c) 2018 International Society for Autism
      Research, Wiley Periodicals, Inc. LAY SUMMARY: Children with autism spectrum
      disorder (ASD) are at a higher risk of having obesity. Yet, it is unknown how
      healthcare providers (HCPs) should deliver weight-related information. Findings
      suggest children and caregivers experienced weight stigma and were uncomfortable
      discussing weight-related issues. HCPs identified that they did not have
      sufficient training, and did not feel confident identifying/addressing weight
      issues. Tools are needed to facilitate weight-related discussions among children,
      caregivers and HCPs.

PMID- 30273980
TI  - Children and Adults Selectively Attribute Shared Cultural Knowledge to Speakers
      of the Same Language.
AB  - Children's and adults' attributions of shared knowledge of and shared preference
      for songs were investigated across two prominent social categories: language and
      gender. Both attributions indicate similarity among individuals but shared
      cultural knowledge can be more informative about common social history than
      shared preference, as it is mainly transferred through social interactions within
      cultures, while preferences can have various sources. Both 5- to 6-year-old
      children (N = 60) and adults (N = 160) generalized knowledge of songs across
      individuals who speak the same-language rather than same-gender individuals. In
      contrast, preference for songs was not systematically generalized across either
      category. Thus, individuals selectively infer shared cultural knowledge among
      same-language speakers, suggesting an early emerging link between shared
      knowledge and cultural boundaries.

PMID- 30273979
TI  - Characterisation of impaired wound healing in a preclinical model of induced
      diabetes using wide-field imaging and conventional immunohistochemistry assays.
AB  - Major complications of diabetes lead to inflammation and oxidative stress,
      delayed wound healing, and persistent ulcers. The high morbidity, mortality rate,
      and associated costs of management suggest a need for non-invasive methods that
      will enable the early detection of at-risk tissue. We have compared the wound
      healing process that occurs in streptozotocin (STZ)-treated diabetic rats with
      non-diabetic controls using contrast changes in colour photography (ie, Weber
      Contrast) and the non-invasive optical method Spatial Frequency Domain Imaging
      (SFDI). This technology can be used to quantify the structural and metabolic
      properties of in-vivo tissue by measuring oxyhaemoglobin concentration (HbO2 ),
      deoxyhaemoglobin concentration (Hb), and oxygen saturation (StO2 ) within the
      visible boundaries of each wound. We also evaluated the changes in inducible
      nitric oxide synthase (iNOS) in the dermis using immunohistochemistry. Contrast
      changes in colour photographs showed that diabetic rats healed at a slower rate
      in comparison with non-diabetic control, with the most significant change
      occurring at 7 days after the punch biopsy. We observed lower HbO2 , StO2 , and
      elevated Hb concentrations in the diabetic wounds. The iNOS level was higher in
      the dermis of the diabetic rats compared with the non-diabetic rats. Our results
      showed that, in diabetes, there is higher level of iNOS that can lead to an
      observed reduction in HbO2 levels. iNOS is linked to increased inflammation,
      leading to prolonged wound healing. Our results suggest that SFDI has potential
      as a non-invasive assessment of markers of wound-healing impairment.

PMID- 30273981
TI  - Associations Between Perceived Material Deprivation, Parents' Discipline
      Practices, and Children's Behavior Problems: An International Perspective.
AB  - This study investigated the association between perceived material deprivation,
      children's behavior problems, and parents' disciplinary practices. The sample
      included 1,418 8- to 12-year-old children and their parents in China, Colombia,
      Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States.
      Multilevel mixed- and fixed-effects regression models found that, even when
      income remained stable, perceived material deprivation was associated with
      children's externalizing behavior problems and parents' psychological aggression.
      Parents' disciplinary practices mediated a small share of the association between
      perceived material deprivation and children's behavior problems. There were no
      differences in these associations between mothers and fathers or between high-
      and low- and middle-income countries. These results suggest that material
      deprivation likely influences children's outcomes at any income level.

PMID- 30273982
TI  - High mobility group box-1 induces pro-inflammatory signaling in human nucleus
      pulposus cells via toll-like receptor 4-dependent pathway.
AB  - Intervertebral disc (IVD) degeneration (DD) is associated with low back pain, the
      leading cause of disability worldwide. Damage-associated molecular patterns
      (DAMPs) that contribute to inflammation and trigger DD have not been well
      characterized. Extracellular high mobility group box-1 (HMGB1) protein has been
      implicated as a potent DAMP and pro-inflammatory stimulus in the immune system.
      In this study, we show that HMGB1 and IL-6 levels increase in patients with
      advanced DD in comparison to early DD. This study further tested the hypothesis
      that HMGB1 promotes inflammatory signaling driving DD in human nucleus pulposus
      (NP) cells and tissue. Immunofluorescence and western blot analysis confirmed the
      expression of HMGB1 and its extracellular release by NP cells under cell stress.
      Gene expression and protein quantification indicate that HMGB1 stimulates the
      expression IL-6 and MMP-1 in a dose-dependent manner. The contributions of toll
      like receptor (TLR) -2, -4 and receptor for advanced glycation end products
      (RAGE) as receptors mediating HMGB1 signaling was examined using small molecule
      inhibitors. Inhibition of TLR-4 signaling, with TAK-242, completely abrogated
      HMGB1 induced IL-6 and MMP-1 expression, whereas inhibition of TLR-2, with O
      vanillin, or RAGE, with FPS-ZM1, had mild inhibitory effects. HMGB1 stimulation
      activated NF-KB signaling while TAK-242 co-treatment abrogated it. Lastly,
      effects of HMGB1 on matrix deposition was evaluated in a 3D culture system of
      human NP cells. These results implicate HMGB1 as a potent DAMP that promotes
      inflammation in NP cells and degradation of NP tissues. TLR4-HMGB1 axis is a
      potential major pathway to alleviate disc inflammation and mitigate DD. (c) 2018
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

PMID- 30273983
TI  - LRH1 as a promising prognostic biomarker and predictor of metastasis in patients
      with non-small cell lung cancer.
AB  - BACKGROUND: LRH1, which promotes the malignant transformation of carcinoma, has
      recently been documented in several types of malignancies. However, LRH1 has not
      been assessed as a potential clinical biomarker in any cancer. METHODS: LRH1
      expression was tested in fresh-frozen tissue samples with quantitative real-time
      PCR and Western blot analysis. Surgically resected tumor tissues were collected
      from 156 non-small cell lung cancer (NSCLC) patients: 75 with adenocarcinoma and
      81 with squamous cell carcinoma. Subsequently, the immunohistochemical expression
      of LRH1 was examined, and its clinical significance was evaluated. RESULTS: LRH1
      overexpression was observed in NSCLC carcinoma tissues compared to adjacent
      normal lung tissues. LRH1 expression was correlated with poorer differentiation
      (P = 0.023), pathological tumor classification (P < 0.001), advanced pathological
      tumor node metastasis stage (P = 0.017), adenocarcinoma subtype (P = 0.031), and
      positive lymph node metastasis (P < 0.001). Multivariate analysis demonstrated
      that LRH1 expression status was an independent prognostic factor for overall
      (hazard ratio 1.372, 95% confidence interval 1.225-1.617; P = 0.003) and disease
      free survival (hazard ratio 1.497, 95% confidence interval 1.059-2.115; P =
      0.011) in patients who suffered from resectable NSCLC. CONCLUSION: The results of
      our study indicate that LRH1 predicts NSCLC progression, metastasis, and a dismal
      prognosis, emphasizing its promising role as a novel target in NSCLC therapies.

PMID- 30273984
TI  - Pressure injury prevention and management practices among nurses: A realist case
      study.
AB  - The prevention and management of a pressure injury is a nurse-sensitive quality
      indicator in hospitals. Prevention and management of pressure injury practices
      have been found to be suboptimal despite the availability of interventions.
      Currently, there is a poor understanding of the mechanisms behind these
      interventions. The aim of the study was to explain a realistic portrayal of
      nurses' current practices to prevent and manage pressure injuries in one public
      hospital in Singapore. A realistic case study design was adopted. Twenty-four
      nurses were recruited. Audio-recorded interviews were transcribed verbatim to
      facilitate thematic analysis. Prevention and management was generally facilitated
      through the timely escalation of care, effective communication, support from the
      wound nurses, and bridging of the knowledge-practice gap. However, factors such
      as nurses' intrinsic characteristics and organisational support may affect the
      outcomes of these facilitators. Overall, nurses strive to achieve patient safety,
      where pressure injuries are prevented to the best of their abilities. This study
      provides causal links between contextual factors, mechanisms of the prevention
      and management, and the outcomes achieved. Further refinement and testing of the
      specific mechanisms are needed and will contribute to a better understanding of
      how nurses prevent and manage pressure injuries.

PMID- 30273986
TI  - Symptomatic venous thromboembolism after non-operatively treated foot or ankle
      injury.
AB  - The purpose was to assess the incidence and risk factors associated with
      symptomatic venous thromboembolism in patients undergoing below knee
      immobilization for non-operative foot or ankle injury. We included all foot and
      ankle patients between January 2005 and May 2016 who underwent non-operative
      management using below knee immobilization with cast, splint, brace, and/or boot.
      The primary outcome was the development of a venous thromboembolism within 90
      days of immobilization initiation. Of 6,088 patients, twenty-three (0.38%)
      developed a venous thromboembolism. Risk factors for venous thromboembolism were
      age>50 years, unremovable immobilization, Achilles tendon rupture, Modified
      Charlson Comorbidity Index>2, patients on chemoprophylaxis, varicose veins,
      history of venous thromboembolism, known hypercoagulability disorder, and
      rheumatoid arthritis. Routine thromboprophylaxis after below-knee immobilization
      for non-operative foot or ankle injury may be beneficial in these specific
      subpopulations. These data can facilitate more substantive shared decision-making
      between providers and patients with respect to use of thromboprophylaxis. (c)
      2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop
      Res.

PMID- 30273987
TI  - Usefulness of bone microarchitectural and geometric DXA-derived parameters in
      haemophilic patients.
AB  - INTRODUCTION: Haemophilia is a recessive X-linked inherited bleeding disorder,
      whose typical symptom is spontaneous intra-articular haemorrhage leading to joint
      damage, which can be quantified by the Haemophilia Joint Health Score (HJHS).
      Arthropathy and other characteristics of haemophilic patients may reduce bone
      mineral density (BMD), increasing the risk for fragility fractures, which also
      may occur due to bone quality impairment. AIM: To evaluate bone quantity by BMD
      and bone quality by Trabecular Bone Score (TBS), bone strain (BS) and hip
      structural analysis (HSA) in a haemophilic population, and to relate these
      parameters to general and specific risk factors for osteoporosis and to HJHS.
      METHODS: Seventy haemophilic patients >=18 years were enrolled. Densitometric
      derived lumbar spine and femoral BMD with TBS, BS and HSA were performed. Data
      regarding risk factors for osteoporosis, presence of arthroprosthesis or
      arthrodesis were collected, and HJHS was calculated. A Z-score <=-2.0 defined a
      low bone mass. RESULTS: Overall, a reduced bone mass was present in 52 patients
      at the femur and in 38 at the lumbar spine. Lumbar spine BMD, TBS and BS did not
      correlate with HJHS. HSA bone geometric parameters correlated negatively with
      HJHS. BMD and HSA correlated with some risk factors for osteoporosis, namely HIV
      and its therapy, hepatitis C and smoking. CONCLUSIONS: Haemophilic patients
      showed a reduced BMD at lumbar spine and/or femur. Femoral bone density and
      geometry correlated with HJHS. The microarchitecture of the trabecular vertebral
      bone seemed to be not influenced by the haemophilic joint damage.

PMID- 30273988
TI  - The mediating role of coping between self-reported health complaints and
      functional limitations, self-assessed work ability and work status of long-term
      sick-listed cancer survivors.
AB  - Our purpose was to investigate the possible mediating role of active coping and
      passive coping between self-reported health complaints and functional
      limitations, as assessed by an insurance physician (IP), self-assessed work
      ability and work status in cancer survivors on long-term sick leave. Validated
      questionnaires were used for self-reported health complaints, work ability and
      work status. The functional limitations of the respondents were transformed into
      scales for mental and physical limitations and limitations in working hours.
      Using LISREL, we constructed a model with coping in a mediating role. Active
      coping mediated between fewer self-reported physical limitations, more depressive
      symptoms, better cognitive functioning and more fatigue on the one hand, and more
      physical limitations and limitations in working hours on the other hand. Passive
      coping played no mediating role and was associated with more self-reported
      depressive symptoms only. More functional limitations were associated with lower
      self-assessed work ability of cancer survivors, and with not being at work,
      whereas higher self-assessed work ability was associated with being at work.
      Regarding the role of active and passive coping strategies in cancer survivors on
      long-term sick leave, more longitudinal research is needed to confirm causality.

PMID- 30273985
TI  - Effect of electroconvulsive therapy on brain-derived neurotrophic factor levels
      in patients with major depressive disorder.
AB  - OBJECTIVES: Brain-derived neurotrophic factor (BDNF) has been associated with
      depression and its treatment response. The aim of the present study was to
      explore the effect of electroconvulsive therapy (ECT) on serum and plasma BDNF
      levels and change of Montgomery-Asberg Depression Rating Scale (MADRS) and their
      associations in patients with major depressive disorder (MDD). METHODS: The study
      included thirty patients suffering from MDD. Their serum and plasma BDNF levels
      were examined before ECT (baseline) and after the first, fifth, and last ECT
      session. The severity of the depression and the response to ECT were measured
      with MADRS. RESULTS: Electroconvulsive therapy caused no significant changes in
      serum BDNF levels. Plasma BDNF levels decreased during the fifth ECT session
      between the baseline and the 2-hr samples (p = 0.019). No associations were found
      between serum or plasma BDNF levels and remission. The correlations between
      plasma and serum BDNF levels in each measurement varied between 0.187 and 0.636.
      CONCLUSIONS: Neither serum nor plasma BDNF levels were systematically associated
      with the clinical remission. However, the plasma BDNF levels somewhat varied
      during the ECT series. Therefore, the predictive value of BDNF for effects of ECT
      appears to be at least modest.

PMID- 30273989
TI  - Iodospirocyclization of Tryptamine-Derived Isocyanides: Formal Total Synthesis of
      Aspidofractinine.
AB  - The N-iodosuccinimide-mediated spirocyclization of tryptamine-derived isocyanides
      to generate spiroindolenines is reported. The products contain both an imine and
      an imidoyl iodide as flexible handles for follow-up chemistry. Nucleophilic
      addition typically occurs chemoselectively on the imine moiety with complete
      diastereoselectivity, providing opportunities for the construction of complex
      molecular frameworks. The synthetic potential of the method was showcased in the
      formal total synthesis of (+/-)-aspidofractinine.

PMID- 30273990
TI  - Changes in and modifiable patient- and family caregiver-related factors
      associated with cancer patients' high self-perceived burden to others at the end
      of life: A longitudinal study.
AB  - This prospective, longitudinal study explored changes in and modifiable factors
      associated with high self-perceived burden to others (SPB) among a convenience
      sample of 276 dyads of terminally ill Taiwanese cancer patients and their family
      caregivers over patients' last year of life. High SPB was evaluated by scores
      >=20 on the Self-Perceived Burden Scale. Modifiable factors of high SPB included
      factors related to both patients (i.e., symptom distress, functional dependence
      and coping capacity) and caregivers (i.e., caregiving burden, depressive symptoms
      and quality of life [QOL]). Modifiable factors of high SPB were identified by
      multivariate logistic regression modelling with the generalised estimating
      equation while controlling for demographic factors. We found that patients tended
      to experience high SPB if they had more symptom distress. In contrast, the
      likelihood of high SPB was significantly lower if patients had greater coping
      capacity and their caregivers reported better QOL. High SPB was not associated
      with patients' functional dependence, caregivers' caregiving burden and
      depressive-symptom level while providing end-of-life (EOL) care, and time
      proximity to death. Healthcare professionals may alleviate terminally ill cancer
      patients' high SPB at EOL through palliative care that adequately manages
      patients' physical symptom distress, enhances patients' coping capacity and
      improves family caregivers' QOL.

PMID- 30273991
TI  - The fate of microplastics during uptake and depuration phases in a blue mussel
      exposure system.
AB  - We present a blue mussel exposure system where the fate of microplastics
      (polystyrene beads) is tracked during exposure and depuration phases. This
      enabled the establishment of a complete mass balance. Quantification of beads in
      mussels was done with a novel enzymatic digestion protocol. We found a similar
      relative distribution of beads for 2 environmentally realistic concentrations (5
      and 100 beads L-1 ) and no substantial egestion of particles within 2 h of
      depuration. Environ Toxicol Chem 2018;9999:1-7. (c) 2018 SETAC.

PMID- 30273992
TI  - Comparative tissue distribution and depuration characteristics of copper
      nanoparticles and soluble copper in rainbow trout (Oncorhynchus mykiss).
AB  - The continuously growing number of products containing nanoparticles (NPs) makes
      their presence in the environment inevitable, and given the well-known toxicity
      of dissolved metals, concerns regarding the toxicity of metal-based NPs have been
      raised. Whether metal-based NPs present similar or different toxicological
      effects compared with metal salts is an emerging field. In the present study,
      rainbow trout were intraperitoneally injected with CuSO4 or copper NPs (CuNPs) to
      investigate tissue distribution and depuration characteristics. Fish injected
      with Cu showed an initial accumulation of Cu in the liver, kidney, gills,
      intestine, and carcass. The Cu concentration in the liver of CuNP-injected fish
      increased over time. It appears as though CuNPs accumulated in the liver at a
      greater rate than they were excreted. In livers of fish injected with CuSO4 , the
      Cu concentration appeared to increase and reach an equilibrium, suggesting that
      copper was accumulated and excreted at the same rate. The possibility that CuNPs
      can accumulate at a higher rate than it is excreted in the liver warrants further
      investigation. The present study demonstrates the possibility of dietary uptake
      of CuNPs because elevated Cu concentrations were observed in carcass, gills,
      kidney, and intestine of fish gavaged with CuNPs. In conclusion, the results
      suggest that dietary CuNPs are taken up by the gut and preferentially accumulate
      in the liver. Environ Toxicol Chem 2018;9999:1-10. (c) 2018 SETAC.

PMID- 30273993
TI  - Radiostereometric analysis of the initial stability of internally fixed femoral
      neck fractures under differential loading.
AB  - We examined the feasibility of radiostereometric analysis (RSA) in the assessment
      of the initial stability of internally fixed femoral neck fractures. The study
      included 16 patients (mean age 73 years). During surgery, multiple RSA-beads were
      inserted on both sides of the fracture. Radiographs for RSA were taken in the
      supine position within the first 3 days and 6, 12, 24, and 52 weeks after
      surgery. To detect any inducible motion at the fracture-site, radiographs for RSA
      were taken with the patient resting or applying a load through the fracture.
      Fracture loading was achieved by the patient pressing the ipsilateral foot as
      much as tolerated on a force plate while providing a counterforce through both
      hands. Micromotion exceeding the precision values of RSA (>=0.3 mm for the
      translation vector and/or >=1.2 degrees for the rotation vector) was considered
      significant. Permanent three-dimensional fracture-site displacement was also
      recorded. Voluntary loading induced fracture-site micromotion, which exhibited a
      dichotomous distribution. In patients with uncomplicated fracture union,
      inducible micromotion was detectable only at baseline-if at all. Conversely,
      fractures that developed a nonunion were characterized by the continuation of
      inducible micromotion beyond baseline. Permanent fracture-site displacement was,
      on average, nearly an order of magnitude greater than the inducible micromotion.
      Fracture unions were characterized by the cessation of permanent fracture-site
      displacement by 12 weeks. Nonunions presented as outliers in permanent fracture
      site displacement. Large-scale studies are warranted to evaluate whether the
      detection of inducible micromotion beyond baseline could serve as an indicator of
      insufficient fixation stability. (c) 2018 The Authors. Journal of Orthopaedic
      Research(r) Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic
      Research Society.

PMID- 30273994
TI  - Group B streptococcus colonisation and associated risk factors among pregnant
      women: A hospital-based study and implications for primary care.
AB  - BACKGROUND: Group B streptococcus (GBS), which asymptomatically colonises the
      vaginal and rectal areas of women, is a leading cause of neonatal mortality and
      morbidity. This study aimed to determine the prevalence and factors associated
      with GBS colonisation among pregnant women in Shenzhen, China. METHODS: A
      hospital-based cross-sectional survey was conducted, using a multistage sampling
      method. Pregnant women at >=28 weeks' gestation completed a questionnaire and
      vaginal swabs were obtained for GBS analysis. Data were analysed by chi-squared
      tests and logistic regression models. RESULTS: The colonisation rate of GBS among
      pregnant women was 4.9%. The influencing factors associated with GBS colonisation
      included body mass index before pregnancy (odds ratio [OR] = 3.79, 95% CI 1.28
      11.26), gestational age (OR = 5.81, 95% CI 1.20-28.15), induced abortion (OR =
      0.63, 95% CI 0.40-0.98) and lotion use before pregnancy (OR = 1.59, 95% CI 1.04
      2.44). CONCLUSIONS: Our findings suggest that obesity, gestational age, induced
      abortion and lotion use were significantly associated with GBS colonisation.
      Further longitudinal research is needed to establish the causal relationship and
      its biological mechanisms.

PMID- 30273995
TI  - Failure loads of all-ceramic cantilever fixed dental prostheses on post-restored
      abutment teeth: influence of the post presence and post position.
AB  - The influence of a fiber post-restored abutment tooth on the load capability of a
      three-unit zirconia framework cantilever fixed dental prosthesis (cFDP) was
      evaluated after simulated clinical function. Human lower sound premolars (n = 64)
      were distributed, in equal numbers, to four experimental groups: two vital
      abutment teeth (group I; control); mesial abutment tooth post-restored (group
      II); distal abutment tooth post-restored (group III); and mesial and distal
      abutment teeth post-restored (group IV). All specimens received an adhesively
      luted three-unit cFDP of veneered zirconia. Simulated clinical function was
      performed by two subsequent sequences of thermal-cycling (2 * 3,000 cycles) and
      mechanical loading (1.2 * 106 load cycles from 0 to 50 N) (TCML). Four specimens
      failed during TCML (one in each of groups I and IV and two in group II). The
      maximum load capability ranged from 365 to 538 N and was not significantly
      different between groups. Specimens with post-restored abutments failed mainly
      because of abutment tooth fracture of the distal abutment. The presence or
      position of post-restored abutment teeth has no significant impact on load
      capability of all-ceramic three-unit cFDPs. The risk of tooth fracture of the
      distal abutment teeth of a cFDP was significantly increased when one abutment
      tooth, irrespective of its position, was post-and-core restored.

PMID- 30273996
TI  - Monte Carlo and 60 Co-based kilovoltage x-ray dosimetry methods.
AB  - PURPOSE: This work seeks to investigate new methods to determine the absorbed
      dose to water from kilovoltage x rays. Current methods are based on measurements
      in air and rely on correction factors in order to account for differences between
      the photon spectrum in air and at depth in phantom, between the photon spectra of
      the calibration beam and the beam of interest, or in the radiation absorption
      properties of air and water. This work aims to determine the absorbed dose to
      water in the NIST-matched x-ray beams at the University of Wisconsin Accredited
      Dosimetry Calibration Laboratory (UWADCL). This will facilitate the use of
      detectors in terms of dose to water, which will allow for a simpler determination
      of dose to water in clinical kilovoltage x-ray beams. MATERIALS AND METHODS: A
      model of the moderately filtered x-ray beams at the UWADCL was created using the
      BEAMnrc user code of the EGSnrc Monte Carlo code system. This model was validated
      against measurements and the dose to water per unit air kerma was calculated in a
      custom built water tank. Using this value and the highly precise measurement of
      the air kerma made by the UWADCL, the dose to water was determined in the water
      tank for the x-ray beams of interest. The dose to water was also determined using
      the formalism defined in the report of AAPM Task Group 61 and using a method that
      makes use of a  RESULTS: The BEAMnrc models used in this work produced
      simulations of transverse and depth dose profiles that agreed with measurements
      with a 2%/2 mm criteria gamma test. The dose to water as determined from the
      different methods used here agreed within 3.5% at the surface of the water tank
      and agreed within 1.8% at a depth of 2 cm in phantom. The dose-to-water values
      all agreed within the associated uncertainties of the methods used in this work.
      Both the Monte Carlo-based method and the  CONCLUSION: Two new dose determination
      methods were used to determine the dose to water in the NIST-matched x-ray beams
      at the UWADCL and they showed good agreement with previously established
      techniques. Due to the improved Monte Carlo calculation techniques used in this
      work, both of the methods have lower uncertainties compared to TG-61. The methods
      presented in this work compare favorably with calorimetry-based standards
      established at other institutions.

PMID- 30273997
TI  - Circulating markers of collagen types I, III, and IV in patients with dilated
      cardiomyopathy: relationships with myocardial collagen expression.
AB  - AIMS: Collagen-derived peptides such as collagen I C-terminal telopeptide (CITP)
      and procollagen III N-terminal propeptide (PIIINP) have been conventionally used
      as markers of cardiac fibrosis. Collagen IV 7S domain (P4NP 7S) has been recently
      reported to be correlated with haemodynamics in patients with acute heart
      failure. We investigated whether these markers reflect cardiac remodelling and
      myocardial collagen expression. METHODS AND RESULTS: In 80 patients with dilated
      cardiomyopathy, relationships of CITP, PIIINP, and P4NP 7S to clinical and
      echocardiographic variables were analysed. CITP and PIIINP were inversely
      correlated with estimated glomerular filtration rate (r = -0.41, P < 0.001 and r
      = -0.32, P = 0.004, respectively); P4NP 7S was positively correlated with B-type
      natriuretic peptide (r = 0.32, P = 0.003) and gamma-glutamyltransferase (r =
      0.38, P < 0.001). These correlations were significant even after adjustment by
      potential confounders, whereas all three collagen markers were not independently
      correlated with ejection fraction nor with left ventricular (LV) diastolic
      diameter. In 33 patients undergoing endomyocardial biopsy, myocardial collagen I
      and III mRNA expressions were correlated with LV end-diastolic volume index (r =
      0.42, P = 0.02 and r = 0.54, P = 0.002, respectively), whereas myocardial
      collagen IV mRNA expression was not correlated with LV end-diastolic volume index
      nor with ejection fraction. Each collagen-derived peptide was not significantly
      correlated with the myocardial expression of their corresponding collagen mRNA.
      CONCLUSIONS: Our study shows that CITP, PIIINP, and P4NP 7S do not reflect
      myocardial collagen mRNA expression but presumably reflect extra-cardiac organ
      injury in heart failure.

PMID- 30273998
TI  - Preimplantation factor modulates acute inflammatory responses of equine
      endometrium.
AB  - Persistent mating-induced endometritis (PMIE) is a significant cause of mare
      infertility hence its treatment would advance the management of susceptible
      mares. Preimplantation factor (PIF) is secreted by viable embryos, including
      human, mouse and cattle, and is essential for maternal immune-tolerance without
      immune-suppression by modulating inflammation. This preliminary study aimed to
      test whether PIF exerts inflammatory-modulating properties upon equine
      endometrium challenged with Escherichia coli-derived lipopolysaccharide (LPS)
      using endometrial explant culture. Follicular (n = 3), luteal (n = 4), anoestrous
      (n = 4) and transitional (n = 4) stage endometrial explants were established and
      cultured in triplicate in either serum-free medium alone (control) or medium
      with; 50 or 100 nmol/L synthetic PIF (sPIF); 3 MUg/mL LPS; LPS and 50 or 100
      nmol/L sPIF; or scrambled PIF (PIFscr; same amino acid composition arranged in a
      different order). Media samples were collected at 24 and 72 h, representing acute
      and chronic inflammatory response. Radioimmunoassay determined Prostaglandin
      F2alpha (PGF2alpha ) as an inflammatory marker. The only significant observation
      was the abrogation of PGF2alpha response to LPS challenge by 100 nmol/L PIF for
      follicular stage tissue, 24 h after treatment. Further studies are therefore,
      warranted to realise PIF potential in managing PMIE.

PMID- 30273999
TI  - Detection of Methylated SEPT9 in Korean Colorectal Cancer Patients: Comparison
      with Previous Studies.
AB  - BACKGROUND: This study aimed to investigate the detection of methylated Septin 9
      (mSEPT9) in Korean patients with colorectal cancer (CRC) and compare the results
      with those of previous studies. METHODS: A total of 127 plasma samples (111
      patients with untreated CRC, 5 patients with adenomas, and 11 CRC patients
      treated with concurrent chemoradiotherapy before surgery) were collected. mSEPT9
      was measured qualitatively with the Abbott RealTime ms9 Colorectal Cancer Assay.
      RESULTS: mSEPT9 was detected in 44 of 111 (39.6%) cases of untreated CRC but was
      not detected in the adenoma cases. The difference in the sensitivity of mSEPT9
      among patients with adenomas and those with each stage of untreated CRC was
      statistically significant (Dukes' staging, p = 0.002 and TNM staging, p = 0.008).
      The sensitivity of mSEPT9 for each of the stages (I - IV) of untreated CRC
      patients were 20.7%, 54.1%, 36.6%, and 75.0%, respectively. The positive mSEPT9
      results in untreated CRC patients reverted to negative in 19 of 21 patients
      (90.5%) after treatment. CONCLUSIONS: Compared to previous studies, the overall
      sensitivity of mSEPT9 was lower, but similar patterns were found in the
      sensitivities for each stage. Additionally, mSEPT9 appeared to have potential as
      a monitoring tool for CRC.

PMID- 30274000
TI  - A Simple and Accurate Measurement Procedure for Serum Chloride by Ion
      Chromatography and Bias Evaluation of Six Ion Selective Electrode Measurements in
      China.
AB  - BACKGROUND: Chloride is the main anion in human body. A simple and accurate
      method for serum chloride measurement was developed using ion chromatography (IC)
      in China. METHODS: In the measurement, serum samples were diluted 500 times with
      water, filtered and injected into ion chromatography column. A mixed eluent (2
      mmol/L CO32- + 12 mmol/L OH-) was used and peak area signal was collected. Five
      calibrators made from Standard Reference Material (SRM) 919b were used in the
      bracketing method. The IC method was applied as the comparative method and six
      ion selective electrode (ISE) measurement systems were evaluated using 60
      individual patient serums. RESULTS: The IC method was proven to be accurate. The
      precision was 0.18% - 0.30%, the recovery was 99.66% - 100.60%, the bias was
      0.19% to -0.06%, and the related expanded uncertainty was 0.775% (k = 2). The
      precisions of the ISE systems were smaller than the 0.9% tolerable CV except for
      the Beckman DXC (0.91% - 1.16%). In comparison, the results of linear regression
      analysis showed that the correlation coefficients were 0.9876 to 0.9979. For all
      systems, the range of mean biases was -5.96 - 1.48 mmol/L (-5.57% - 1.36%); the
      expected biases at the medical decision levels were -4.97% - 0.84% at 90 mmol/L
      and -6.02% - 1.76% at 120 mmol/L. All biases of the Beckman AU met the
      requirement of within +/- 1.5%. CONCLUSIONS: The IC measurement method is proven
      to be of high precision and trueness, and the quality of routine ISE measurement
      of serum chloride still needs significant improvement. The establishment of the
      IC method can improve the measurement quality and promote its standardization
      process in China.

PMID- 30274001
TI  - Serum Soluble ST2 as a Novel Inflammatory Marker in Acute Ischemic Stroke.
AB  - BACKGROUND: Soluble ST2 (sST2) receptor is secreted and detectable in human
      serum, which acts as a decoy receptor for interleukin (IL)-33 to prevent IL-33
      mediated Th2 immune responses. Recently, elevated serum sST2 has been found to be
      a novel biomarker in cardiovascular diseases such as heart failure and
      atherosclerosis. Here, we studied the role of sST2 in acute ischemic stroke (AIS)
      and its relationship with several inflammatory markers. METHODS: The study
      included 112 patients with first-ever acute ischemic stroke, who were admitted
      within 48 hours after stroke onset. The serum levels of sST2 and IL-33 were
      measured with ELISA and the severity of AIS patients was evaluated based on the
      National Institutes of Health Stroke Scale (NIHSS) score. The cerebral infarct
      volume was calculated according to the Pullicino formula based on the cranial CT
      scan or MRI. High-sensitivity C-reactive protein (hs-CRP) and serum amyloid A
      protein (SAA) were measured using the latex-enhanced immunoturbidimetric assay.
      RESULTS: The serum sST2 level was significantly increased in patients with AIS
      compared to the control patients without AIS. In addition, the concentration of
      serum sST2 increased with the infarct volume and the severity of AIS evaluated
      based on the NIHSS score. Furthermore, the sST2 level correlated positively with
      the inflammatory marker hs-CRP. CONCLUSIONS: Our study suggests that sST2 may be
      used as a novel diagnostic and predicting inflammatory marker in AIS.

PMID- 30274002
TI  - Expression of Long Non-Coding RNA PRAL as a Potential Biomarker for Diagnosis in
      Non-Small-Cell Lung Cancer Patients is Associated with the Inhibition of Cell
      Proliferation and Metastasis.
AB  - BACKGROUND: Accumulating evidence reveals that long non-coding RNAs (lncRNAs)
      play a crucial role in pathogenesis of non-small-cell lung cancer (NSCLC),
      providing a new concept to exploit novel biomarkers for diagnosis, prognosis or
      therapeutic target of NSCLC. The intention of this study was to examine the
      viability of lncRNA PRAL as a biomarker for NSCLC and explore its biological
      function in NSCLC cell lines. METHODS: PRAL transcription levels were evaluated
      using Q-PCR. Receiver operating characteristic (ROC) curve analyses were used to
      evaluate the diagnostic value for NSCLC patients. Kaplan-Meier analysis and log
      rank test were performed to assess the correlation between PRAL expression and
      the clinical outcomes on overall survival (OS) and progression-free survival
      (PFS). RESULTS: PRAL expression levels were prominently decreased in a majority
      of the NSCLC tumor tissues compared with corresponding adjacent normal tissues (p
      < 0.0001) and healthy tissues (p < 0.0001). Receiver operating characteristic
      (ROC) curve analyses indicated strong separation between the NSCLC tissues and
      the control group, with an AUC of 0.8546 (95% CI: 0.7993 to 0.9098; p < 0.0001)
      for PRAL. Using the Chi-square test showed an obvious negative correlation
      between down-regulated PRAL levels and advanced TNM stage (chi2 = 8.826, p =
      0.003). High PRAL levels had a longer median OS and median PFS (median OS, 42
      months vs. 33.5 months, p = 0.0122; median PFS, 30 months vs. 24.5 months, p =
      0.0317). Univariate and multivariate analysis of clinical pathological factors
      were also performed. In addition, over-expression of PRAL blocked
      proliferation,migration, and invasion in NSCLC cell lines. CONCLUSIONS: Taking
      these results together, PRAL expression level could be a potential biomarker for
      diagnosis in NSCLC patients.

PMID- 30274003
TI  - Clinical Value of Human Papillomavirus E6/E7 mRNA Detection in Screening for
      Cervical Cancer in Women Positive for Human Papillomavirus DNA or.
AB  - BACKGROUND: The detection of human papillomavirus (HPV) E6/E7 mRNA indicates a
      risk of further deterioration in cervical lesions. We explored the clinical value
      of HPV E6/E7 mRNA detection in cervical cancer screening in women positive for
      HPV or with abnormal thin-prep cytology test (TCT) results in the Xinjiang region
      of China. METHODS: A total of 6,800 women were screened in our hospital for
      cervical cancer by both TCT and HPV DNA testing from August 2013 to June 2015. Of
      these, 197 had abnormal cytological or HPV test results and subsequently
      underwent HPV E6/E7 mRNA detection and histopathological examination, while 101
      underwent an HPV DNA typing test. Using pathological results as the gold
      standard, we compared the accuracies of HPV E6/E7 mRNA detection or HPV DNA type
      testing alone, in parallel, and in series for diagnosing high-grade cervical
      lesions. RESULTS: Pathological examination revealed 80 cases of chronic
      cervicitis, 16 cases of cervical intraepithelial neoplasia (CIN)-I, 50 cases of
      CIN-II-III, and 51 cases of cervical cancer. The area under the receiver
      operating characteristic (ROC) curve (AUC) for diagnosing high-grade cervical
      lesions by HPV E6/E7 mRNA detection was 74.95% (sensitivity, 85.15%; specificity,
      66.67%; Youden index, 0.139; positive predictive value, 72.9%; negative
      predictive value, 81.0%; positive likelihood ratio, 2.555; negative likelihood
      ratio, 0.222; and post-test probability, 72.9%). CONCLUSIONS: HPV E6/E7 mRNA
      detection is superior to HPV DNA type testing for diagnosing high-grade cervical
      lesions.

PMID- 30274004
TI  - Thrombin Generation Testing in Patients with Myelofibrosis.
AB  - BACKGROUND: Primary myelofibrosis (PMF) is a chronic clonal myeloid disorder.
      Together with essential thrombocythemia (ET) and polycythemia vera (PV), it
      belongs to a group of Philadelphia chromosome-negative myeloproliferative
      neoplasms. Thrombotic events are serious complications negatively influencing the
      quality and length of these patients' lives. The confirmed risk factors for
      venous thromboembolism are age over 60 years, a positive history of
      thromboembolism, presence of common cardiovascular risks, JAK2 V617F mutation
      and, according to some authors, leukocytosis. Various opinions on the role of
      thrombocythemia have been published. The present study was undertaken to evaluate
      the benefit of thrombin generation test and its potential use in predicting the
      risk of thrombosis in MF patients. METHODS: The analysis included plasma samples
      obtained from 36 patients diagnosed with MF in our center from 2004 to 2016 (JAK2
      V617-positive 53%; CALR-positive 31%; MPL-positive 14%; triple negative 2%) and a
      control group comprising 20 healthy volunteer blood donors. Thrombin generation
      was measured in platelet-rich plasma using the TECHNOTHROMBIN(r) TGA kit
      (Technoclone, Austria) and the fully automated system Ceveron(r) Alpha
      (Technoclone). The results were correlated with clinical and laboratory
      parameters of the patients. RESULTS: There were differences in thrombin
      generation as expressed by endogenous thrombin potential (ETP) between patients
      and healthy controls, with ETP being lower in the patient group (p = 0.0003).
      Analysis confirmed a significant correlation between thrombin generation and
      platelet counts, with higher thrombin generation in patients with thrombocythemia
      > 400 x 109/L (p = 0.04). ETP values were consistently higher in earlier disease
      stages and lower in CALR-mutated myelofibrosis. CONCLUSIONS: In MF patients,
      thrombin generation is mainly influenced by platelet counts and, to a lesser
      extent, by mutation status, activity, and progression of the disease. Thrombin
      generation test results have confirmed that thrombocythemia is a potential risk
      factor for thrombotic complications.

PMID- 30274005
TI  - The Association between Infertility and Helicobacter pylori Infection: a Meta
      Analysis of Case-control Studies.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is increasingly associated with extra
      digestive diseases. Infertility is a common condition, with an incidence of 10 to
      15% of couples. Studies examining the association of H. pylori infection and
      infertility have reported conflicting results. This meta-analysis aimed to
      investigate the association between H. pylori infection and infertility. METHODS:
      Studies of H. pylori infection and infertility were identified in PubMed, EMBASE,
      the Cochrane Library, and China National Knowledge Infrastructure. We performed a
      meta-analysis of all case-control studies. RESULTS: Seven studies that analyzed
      the relationship between H. pylori infection and infertility, with a combined
      study population of 1,902 patients, were included in the meta-analysis (n = 626
      for patients; n = 1,276 for controls). In the infertility group, 344 (54.9%)
      patients were H. pylori-positive, and 495 (38.8%) were H. pylori-positive in the
      control group. Our result suggested that H. pylori infection was associated
      significantly with infertility (OR = 1.45, 95% CI: 1.197 - 2.160; I2 = 36.5%, Z =
      3.15, p = 0.002). Begg's and Egger's funnel plot showed no publication bias (p =
      0.807). CONCLUSIONS: Our meta-analysis identified a possible association between
      H. pylori infection and infertility.

PMID- 30274006
TI  - Neutrophil-to-Lymphocyte Ratio as a Potential Early Marker of Antibiotic
      Resistance in Patients with Infected Cirrhotic Ascites.
AB  - BACKGROUND: To evaluate the role of neutrophil-to-lymphocyte ratio (NLR) in
      identification and management of infected ascites among patients with cirrhosis.
      METHODS: A total of 439 patients (mean (SD) age: 64.5 (+/- 12.7) years, 63.3%
      were males) hospitalized with cirrhotic ascites were included in this
      retrospective study. Data on patient demographics, etiology of cirrhosis, type of
      ascites (sterile ascites, infected ascites), culture findings treatment response
      (antibiotic resistance vs. sensitivity) and baseline (Day 0), Day 1 and Day 2
      levels for serum C-reactive protein (CRP; mg/L), and NLR were recorded. Receiver
      operating characteristics (ROC) curve was plotted to determine performance of %
      change from baseline NLR on Day 1 in identifying treatment response. RESULTS: In
      patients with infected ascites, antibiotic resistant patients had significantly
      higher Day 1 (6.9 (1.9 - 74.9) vs. 4.9 (1.1 - 51.1), p = 0.001) and Day 2 (8.0
      (2.6 - 75.9) vs. 4.0 (1.1 - 40.3), p = 0.000) levels for NLR as compared with
      antibiotic sensitive patients, while the two groups had similar baseline (Day 0)
      NLR values (5.8 (1.1 - 62.3) vs. 5.7 (1.1 - 72.3), p = 0.969). ROC analysis
      revealed less than 0.93% decrease from baseline NLR on Day 1 (AUC (95% CI): 0.852
      (0.799 - 0.895), p < 0.001) to be a potential marker of antibiotic resistance
      with a sensitivity of 87.72% and specificity of 88.50%. CONCLUSIONS: Our findings
      indicate percent change from baseline NLR on Day 1 to be a potential early marker
      of antibiotic resistance in patients with infected cirrhotic ascites. Our
      findings emphasize the role of determining NLR levels in earlier recognition of
      treatment failure and thus prompt modification of antibiotic treatment in
      cirrhotic patients with infected ascites.

PMID- 30274007
TI  - Effects of Freeze-Thaw Times on Screening Coagulation Tests and Factors VIII and
      IX Activities in Citrate-Anticoagulated Plasma at -20 degrees C and -80 degrees
      C.
AB  - BACKGROUND: Accurate determination of screening coagulation tests and factors
      VIII and IX activities (FVIII:C and FIX:C) in fresh plasma is very important for
      diagnosing abnormalities in the intrinsic or extrinsic coagulation pathways and
      factor deficiencies. If thawed samples cannot be detected for all required items
      at the same time, or need to be re-tested or re-stored, the thawed samples need
      to be re-frozen. We planned to perform in-house validation studies on freeze
      thawed samples for screening coagulation tests, FVIII:C and FIX:C. METHODS: Mean
      percent changes, numbers of samples with > 10% changes, and difference plots were
      evaluated to determine clinically relevant differences between results for fresh
      and freeze-thawed samples. The statistical significance of differences between
      repeated-measure multiple groups and baseline values were evaluated by repeated
      measures analysis of variance. RESULTS: The acceptable freeze-thaw cycles for
      activated partial thromboplastin time, fibrinogen, prothrombin time/international
      normalized ratio, thrombin time, and FIX:C were three times at -20 degrees C/-80
      degrees C, while the acceptable freeze-thaw cycles for FVIII:C were three times
      at -80 degrees C and once at -20 degrees C. CONCLUSIONS: The freeze-thaw results
      on stabilities were affected by time and temperature, with lower temperature and
      fewer times associated with more stable activity.

PMID- 30274008
TI  - Comparison of Three Routine Methods for the Measurement of Serum Bilirubin in a
      China Laboratory.
AB  - BACKGROUND: The reliability of bilirubin measurements is not satisfactory due to
      the marked variability of methodologies since discovery. METHODS: Imprecision of
      the three analytical systems (diazo method, vanadate oxidase method, and dry
      chemistry method) were calculated in accordance with CLSI guidelines EP15-A2.
      According to Clinical and Laboratory Standards Institute (CLSI) guideline (EP9
      A2), 40 analytes were detected to evaluate method performance and comparability
      among three routine measurements for serum bilirubin in a China laboratory.
      RESULTS: The within-run precisions and the intermediate imprecision of the three
      methods all met the CLIA'88 requirement of bilirubin measurement. All three
      evaluated methods were closely correlated with correlation coefficients ranging
      from 0.995 to 0.999. The 95% predicted bias confidence intervals between diazo
      method and vanadate oxidase method for total bilirubin were acceptable. However,
      for direct bilirubin, the 95% predicted bias confidence intervals was only
      acceptable at the medium medical decision point. The 95% predicted bias
      confidence intervals between diazo method and dry medical method for total
      bilirubin was all acceptable. CONCLUSIONS: All three evaluated routine methods
      for serum bilirubin in our lab were closely correlated. For measurements of total
      and direct bilirubin, both dry medical method and vanadate oxidase method had
      significant differences compared with the diazo method. Further studies are
      required to reduce the biases among these methods.

PMID- 30274009
TI  - The Association Between Serum Uric Acid Level and Prognosis in Critically Ill
      Patients, Uric Acid as a Prognosis Predictor.
AB  - BACKGROUND: Uric acid is synthesized from xanthine via xanthine oxidase as an end
      product of purine metabolism. Uric acid is a major non-enzymatic antioxidant in
      the blood, and it exerts a protective action on vitamin C. There are a limited
      number of ICU studies related to uric acid, which is a valuable prognostic
      biomarker. This study aimed to evaluate the utility of uric acid as a biomarker
      in predicting the outcomes of critically ill patients. METHODS: This prospective,
      multi-centered cohort study included 128 patients from two different intensive
      care units who met the study inclusion criteria between May 2017 and October
      2017. Study inclusion criteria were first admission to the ICU, age > 18 years,
      and ICU stay > 24 hours. In each patient, baseline serum uric acid levels were
      measured after acute interventions, prior to the initiation of the treatment
      process. RESULTS: When comparing the last uric acid levels of patients, the
      median last uric acid levels in the non-survival and survival groups were
      significantly different (p = 0.001). A last uric acid level > 4.5 mg/dL was
      associated with a 2.638 times higher risk (relative risk) for mortality.
      According to ROC analysis, a cutoff value of 1.5 for the ratio between the last
      two uric acid levels had a sensitivity of 0.21 and a specificity of 0.96 for
      predicting mortality. A 1.5-fold increase in the uric acid level yielded a
      positive predictive value of 92.6% and a negative predictive value of 65.2% for
      predicting mortality. The median uric level in the patient subset with ARDS, was
      significantly higher than those without ARDS (p = 0.001). CONCLUSIONS: Results of
      this study indicate that a time-dependent increase in uric acid levels can be
      used as an important biomarker for predicting mortality in critically ill
      patients; further, uric acid levels should possibly be included in the current
      mortality risk scoring systems. In addition, elevation of uric acid, a simple,
      inexpensive, and readily available biomarker, may provide guidance in the
      diagnostic stage and in predicting clinical outcomes of patients with sepsis or
      ARDS.

PMID- 30274010
TI  - Transient EDTA-Dependent Pseudothrombocytopenia Phenomenon in a Patient with
      Antiphospholipid Syndrome.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disorder associated with
      arterial/venous thrombosis and pregnancy loss; thrombocytopenia is another common
      manifestation of APS. In the present study, we discovered a transient
      ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (EDTA-PTCP)
      phenomenon in APS, which has not yet been reported in the literature.

PMID- 30274011
TI  - Laboratory Impact of Rapid Molecular Tests used for the Detection of Respiratory
      Pathogens.
AB  - BACKGROUND: With outbreaks of new respiratory viruses such as the severe acute
      respiratory syndrome coronavirus and swine-origin influenza A/H1N1, the nucleic
      acid-based amplification test was introduced to identify causative agents.
      Multiplex PCR, which can simultaneously detect various respiratory pathogens, is
      currently used worldwide. Recently, a new type of multiplexed molecular test
      using a fully automated workflow system was developed, which was also adapted to
      our laboratory. In this study, we assessed improvements in laboratory practice
      brought about by the implementation of the rapid test for the detection of
      respiratory viruses. METHODS: We investigated the number of routine and rapid
      tests conducted as well as the change in monthly test frequency of the routine
      test. We also analyzed the waiting time, turnaround time, and lead time for the
      routine and rapid tests. The Anyplex II RV16 detection kit (Seegene, Seoul,
      Korea) and Filmarray Respiratory Panel (BioFire Diagnostics, Inc., Salt Lake
      City, UT, USA) were used for the routine and rapid tests, respectively. RESULTS:
      Compared to the routine test, the rapid test significantly (p < 0.01) decreased
      the mean waiting time (1 hour 46 minutes), turnaround time (1 hour 45 minutes),
      and lead time (3 hours 32 minutes). After the implementation of the rapid test,
      the number of routine tests conducted was reduced over the 5-month period, from
      13 times a month to 3 times a month. CONCLUSIONS: The implementation of the rapid
      test for the detection of respiratory viruses improved the diagnostic efficiency
      of the laboratory and greatly reduced lead time.

PMID- 30274012
TI  - Relationship Between SLC22A1 and SLC22A4 Gene Polymorphisms and Risk of Type 2
      Diabetes in Chinese Han Population.
AB  - BACKGROUND: This study was to investigate the relationship between SLC22A1 and
      SLC22A4 gene polymorphisms and genetic susceptibility to type 2 diabetes in
      Chinese Han population. METHODS: The research group comprised 110 Chinese Han
      patients with type 2 diabetes, and the control group included 110 healthy
      volunteers. The polymorphisms of SLC22A1 gene rs628031 and rs2282143 loci and
      SLC22A4 gene rs2073838 and rs272893 loci were detected in the two groups.
      RESULTS: Statistically significant differences were identified in the genotype
      distributions of SLC22A1 gene rs628031 and rs2282143 loci between the two groups
      (p < 0.05). The A allele frequency of SLC22A1 gene rs628031 locus and the T
      allele frequency of rs2282143 locus were higher in the research group than in the
      control group (p < 0.05). The genotype distributions of rs272893 locus showed a
      significant difference between the two groups (p < 0.05), but not SLC22A4 gene
      rs2073838 locus (p > 0.05). CONCLUSIONS: The polymorphisms of SLC22A1 gene
      rs628031 and rs2282143 loci and SLC22A4 gene rs272893 locus of patients with type
      2 diabetes indicated a significant difference between the two groups, suggesting
      that these genetic locus mutations increase the risk of type 2 diabetes in
      Chinese Han patients.

PMID- 30274013
TI  - First-Trimester Biochemical Screening For Low Birth Weight: Clinical
      Effectiveness of Low Pregnancy-Associated Plasma Protein-A and High Thyroid
      Stimulating Hormone.
AB  - BACKGROUND: Low birth weight (LBW) can be an important adverse neonatal outcome
      in terms of morbidity and mortality. The aim of this study is to investigate the
      screening effectiveness of first-trimester low pregnancy-associated plasma
      protein A (PAPP-A) and high serum thyroid-stimulating hormone (TSH) and the
      combination of both markers for predicting LBW. METHODS: We performed a
      retrospective cohort study of women undergoing first-trimester assessment in our
      center. We considered low PAPP-A as < 5th percentile for gestational age. High
      serum TSH was defined as > 2.5 mU/L, according to the American Thyroid
      Association (ATA) recommendation. Receiver-operating characteristic (ROC) curves
      were plotted to evaluate screening performance. Multivariate logistic regression
      was accomplished to calculate adjusted risks to identify the association between
      both parameters with LBW. RESULTS: Overall, 4,396 women met the inclusion
      criteria. Of these, 277 (6.3%) delivered a LBW baby. The use of either low PAPP-A
      or high TSH yielded the highest sensitivity (21.1%) with a specificity of 85.7%.
      Combining both markers showed an increased association (adjusted OR 9.07 [95% CI
      3.34 - 24.6]) at the expense of a significant reduction in sensitivity (7.8%).
      CONCLUSIONS: First-trimester low PAPP-A is associated with LBW at delivery.
      Neither of these biomarkers or their combination are acceptable predictors to be
      clinically useful tools for LBW.

PMID- 30274014
TI  - Alteration of Serum 25(OH) Vitamin D, Vitamin D Binding Protein, and C-reactive
      Protein Levels in Acute Leukemia Patients.
AB  - BACKGROUND: Acute leukemia is a common hematologic malignancy with poorly
      differentiated leukocytes. Alteration of circulating vitamin D (VD) and its
      carrier vitamin D binding protein (VDBP) have been reported in certain types of
      cancers and may play a role in the course of the disease. Understanding of the
      status of serum VD and VDBP, as well as the acute phase protein C-reactive
      protein (CRP) levels in pre- and post-treatment of acute leukemia patients, may
      be helpful in the management of acute leukemia. METHODS: Enzyme linked
      immunosorbent assay (ELISA), chemiluminescence immunoassay, and immunofluorescent
      assay were used to analyze the 25(OH) vitamin D (25(OH)D), VDBP, and CRP in the
      serum of a cohort of leukemia patients. RESULTS: Serum 25(OH)D levels in patients
      (pre- and post-treatment) were significantly lower than in control subjects.
      There was no significant difference in 25(OH)D levels between pre- and post
      treatment. Serum VDBP level was raised in both pre- and post-treatment of acute
      leukemia patients, with that of pre-treatment being higher. The average serum
      VDBP was reduced in post-treatment; however, no significant difference was found.
      Elevated serum CRP levels in both pre- and post-treatment patient groups have
      been observed but were reduced significantly after treatment. Results also
      revealed that serum VDBP levels in acute myeloid leukemia patients were
      significantly higher than in acute lymphoid leukemia patients, while 25(OH)D
      levels in acute myeloid leukemia were significantly lower than in acute lymphoid
      leukemia. No significant difference between the serum CRP levels of acute myeloid
      leukemia and acute lymphoid leukemia was observed. CONCLUSIONS: Serum 25(OH)D,
      VDBP, and CRP may be used together and could be potential indicators of the
      disease course of acute leukemia and assist in its management which merits
      further investigation.

PMID- 30274015
TI  - NOB1 Gene as a Potential Biomarker in Clinical Outcomes and Prognosis of Patients
      with Gastric Cancer.
AB  - BACKGROUND: To investigate relationship of the Nin one binding protein (NOB1)
      gene with the prognosis of gastric cancer (GC). METHODS: The GC tumor tissues and
      paired adjacent normal gastric tissues were collected from 65 patients who
      underwent primary gastric resection surgery in our hospital from January 2009 to
      July 2011. Data including age, gender, family cancer history, tumor diameter,
      pathological type, differentiation, clinical stage by tumor node metastasis (TNM)
      staging, lymphatic metastasis, and distant metastasis were collected. Expression
      of NOB1 and VEGF was determined using real time PCR. The relationship of NOB1
      with clinical outcomes and prognosis of GC patients was analyzed by statistical
      methods. RESULTS: Both mRNA expression of NOB1 and VEGF was significantly higher
      in tumor tissues than that of the normal tissues, p < 0.05, and mRNA expression
      of NOB1 was positively correlated with mRNA expression of VEGF by Pearson's
      correlation analysis. Significant difference was observed in TNM stage, tumor
      differentiation, and metastasis between the low and high NOB1 expression groups,
      p < 0.05, while no significant difference was observed in age, gender, family
      cancer history, tumor location, and diameter. Univariate analysis showed that TNM
      stage, tumor differentiation, lymphatic metastasis, distant metastasis and
      expression of NOB1 and VEGF were all significantly different in survival and dead
      patients. Logistic analysis showed that NOB1 was an independent risk factor for 5
      year mortality of GC patients, as well as lymphatic metastasis and distant
      metastasis. CONCLUSIONS: NOB1 was correlated with clinical outcomes and prognosis
      of GC patients and was an independent risk factor for 5-year mortality of GC
      patients. This study might provide more clinical evidences for NOB1 in GC and
      give a new target for diagnosis and treatment for GC patients.

PMID- 30274016
TI  - Performance of LC/MS/MS in Analyzing Multiple Amino Acids and Acylcarnitines in
      Dried Blood Spot of Very Low Birth Weight, Low Birth Weight, and Normal Weight
      Neonates.
AB  - BACKGROUND: Amino acid (AA) and acylcarnitine (AC) are important biomarkers of
      protein and fatty acid metabolism. Examining their levels in newborns may reveal
      multiple inherited metabolic diseases. However, they have rarely been assessed in
      very low birth weight (VLBW) neonates, low birth weight (LBW) neonates and rarely
      been compared with normal weight (NW) neonates. The aim of the study was to
      identify the AA and AC profiles in dried blood spot (DBS) specimens of LBW and
      VLBW neonates, then compare with NW neonates, and make a contribution to the
      determination of cutoff values of VLBW and LBW neonates. METHODS: Liquid
      Chromatography tandem mass spectrometry (LC/MS/MS) is an excellent tool for
      quantitatively detecting AA and AC profiles. This article verified the precision,
      accuracy, and linearity of the LC/MS/MS method in AA and AC detection, then
      analyzed AA and AC profiles in DBS of VLBW, LBW and NW neonates, and compared the
      difference of AA and AC in the three groups. RESULTS: The results showed that the
      LC/MS/MS method had wide linear range, satisfied precision and reproducibility in
      detecting AA and AC in DBS specimens; most AA and AC concentrations significantly
      correlated with birth weight in DBS samples (p < 0.05). CONCLUSIONS: The results
      suggested that VLBW and LBW neonates have different metabolic or nutritional
      status with NW neonates and different AA and AC cutoffs should be defined for
      them to reduce the risk of false-positive cases.

PMID- 30274017
TI  - The Diagnostic Performance of Urine Flow Cytometer UF1000i for Urinary Tract
      Infections.
AB  - BACKGROUND: Urinary tract infections (UTIs) are one of the most common infectious
      diseases in clinic. Urine flow cytometry is receiving more and more attention due
      to its rapid forecast of UTIs. METHODS: The Urine Flow Cytometer UF1000i has a
      series of software programs to quantify bacteria (BACT) and white blood cells
      (WBC), and describe the scatter diagram of bacteria. The UTIs were predicted
      based on the cutoff values with the Receiver Operating Characteristic (ROC)
      curves of BACT and WBC counts. To evaluate the diagnostic performance of UF1000i
      for UTIs, the sensitivity and specificity of 889 urine samples were determined in
      comparison to the results of urine culture. Meanwhile the bacterial morphology
      indication of the UF1000i was evaluated in order to help doctors choose
      antibiotics. The angle of the scatter cloud with the x-axis was used to classify
      the infected bacteria as bacilli (< 30 degrees ) or cocci (>= 30 degrees ).
      RESULTS: The best cutoff value of BACT counts for predicting UTIs was 119 per uL,
      and the sensitivity and specificity were 95.5% and 88.7%, respectively. While the
      best cutoff value of WBC counts was 81.5 per uL, and the sensitivity and
      specificity were 77.6% and 76.7%, respectively. In addition, the best cutoff
      values for females were 583 BACT per uL and 137.5 WBC per uL. They were much
      higher than for males (118 BACT per uL and 91 WBC per uL). The coincidence of the
      bacterial morphology information between the UF1000i software indication and the
      bacterial actual morphology identified by urine culture was 83% (bacilli) and 68%
      (cocci), respectively. CONCLUSIONS: Data demonstrated that the performance of
      BACT counts for UTIs is superior to WBC counts. In addition, the bacterial
      morphology could preliminarily be predicated by the scatter diagram. Since the
      urine flow cytometer UF1000i can provide the data of both BACT counts and the
      scatter diagram, the urine flow cytometry was regarded as a suitable method for
      screening UTIs. Moreover, it would be better to take gender into consideration
      when setting the best cutoff value for diagnosis of UTIs in clinic.

PMID- 30274019
TI  - Serum Human Epididymis Secretory Protein 4 (HE4) is a Potential Prognostic
      Biomarker in Non-Small Cell Lung Cancer.
AB  - BACKGROUND: Human epididymis secretory protein 4 (HE4) is a secreted glycosylated
      protein belonging to the WFDC family, which is an ideal biomarker in ovarian
      cancer. However, the role of HE4 in lung cancer is still unclear. The study aimed
      to evaluate serum levels of HE4 as a prognostic biomarker in patients with non
      small cell lung cancer (NSCLC). METHODS: The subjects consisted of 217 NSCLC
      patients, which were compared to a control group of 80 patients with benign lung
      disease and 110 healthy controls. Serum levels of HE4 were measured with
      electrochemiluminescence assays in a Roche E601 Immunoassay Analyzer. RESULTS:
      Serum levels of HE4 in NSCLC patients were significantly higher than in benign
      lung disease and healthy controls (p < 0.001). Using the cutoff value of 78.84
      pmol/L, HE4 levels differentiated NSCLC from healthy controls with a sensitivity
      of 84.2% and a specificity of 78.3%. In the NSCLC subgroups, HE4 was a better
      discriminator of lung adenocarcinoma (cutoff value, 72.70 pmol/L, area under
      curve, 0.909; 95% confidence interval, 0.871 - 0.947). Higher serum HE4 levels
      were significantly correlated with histological type, high TNM stage, and
      positive lymph node metastasis (p = 0.019, 0.018, 0.002, respectively). Kaplan
      Meier analysis demonstrated that high HE4 levels predicted poor survival (log
      rank test: p = 0.007), especially in the adenocarcinoma group (logrank test: p =
      0.001). In the Cox model, serum HE4 level was an independent prognostic factor
      for NSCLC. CONCLUSIONS: Higher serum levels of HE4 predict poor prognosis in
      NSCLC patients, especially in patients with adenocarcinoma.

PMID- 30274018
TI  - Decreased Serum Lipid Levels and Ratios Correlate with Low Prevalence of Coronary
      Heart Disease in Patients with Parkinson's Disease.
AB  - BACKGROUND: Patients with Parkinson's disease (PD) are at a lower risk of
      suffering cardiovascular events, but the underlying factors for this decreased
      risk remain unclear. Serum triglycerides (TG) and total cholesterol (TC), and
      their expression relative to high-density lipoprotein cholesterol (TG/HDL-C and
      TC/HDL-C), are independent predictors of cardiovascular events. This study aimed
      to determine if PD patients have decreased lipid levels and lipid ratios, which
      may underlie the decreased risk of coronary heart disease (CHD). METHODS: This
      retrospective study included 92 PD patients (PD group), 450 control subjects with
      no CHD (OD group), and 450 CHD patients (CHD group). We analyzed serum lipid
      levels and lipid ratios in each group. RESULTS: There were significant
      differences in TC (F = 10.459, p < 0.0001), TG (F = 46.856, p < 0.0001), low
      density lipoprotein cholesterol (LDL-C) (F = 6.910, p = 0.001), high density
      lipoprotein cholesterol HDL-C (F = 30.694, p < 0.0001), TC/HDL-C (F = 32.675, p <
      0.0001), and TG/HDL-C (F = 45.554, p < 0.0001) between all three groups; TC/LDL-C
      (F = 2.518, p = 0.081) was not significantly different between groups. Compared
      to the CHD group, PD patients had lower TC (p < 0.0001), TG (p < 0.0001), LDL-C
      (p = 0.001), TG/HDL-C (p < 0.0001), and TC/HDL-C (p < 0.0001); TC/LDL-C (p =
      0.563) and HDL-C (p = 0.196) were not significantly different. TC and LDL-C
      levels were positively correlated within individual groups (all p < 0.0001). In
      addition, TG and HDL-C were negatively correlated in the OD and CHD groups (p <
      0.0001); no significant negative association was observed in the PD group (p =
      0.077). TG/HDL and LDL-C levels were inversely correlated in the CHD group (p <
      0.0001) and weakly positively correlated in the PD (p = 0.159) and OD (p = 0.199)
      groups. CONCLUSIONS: TC/HDL and TG/HDL ratios were significantly lower in PD
      patients compared to CHD patients, suggesting there is a strong correlation
      between lipid ratios and incidence of CHD in PD patients.

PMID- 30274020
TI  - Prognostic Implication of MIF Gene Expression in Childhood Acute Lymphoblastic
      Leukemia.
AB  - BACKGROUND: Cytogenetic and molecular genetic markers have been used recently to
      stratify risk and predict prognosis of different types of cancers. Macrophage
      migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays an
      important role in the pathogenesis of many diseases, such as autoimmune diseases
      and cancers. We studied MIF gene expression behavior to investigate its
      prognostic impact in childish patients with acute lymphoblastic leukemia (ALL).
      METHODS: MIF expression was analyzed using quantitative real-time (QRT) PCR.
      Patients are classified into two groups, high and low MIF expressers, according
      to median MIF gene expression. RESULTS: We did not find any significant
      difference between both groups as regards the clinical and hematological picture.
      However, high MIF expressers had significantly lower incidence of CR (25.8% vs.
      72.4%, p = 0.001), higher incidence of refractory (51.6% vs. 24.1, p = 0.029),
      relapse rates (19.4% vs. 10.3%, p = 0.32), and higher mortality rate (54.8% vs.
      20.7, p = 0.007) than lower MIF expressers. In addition, high MIF expressers show
      significantly shorter DFS (12.48 vs. 25.11 months, cumulative survival 38.7% vs.
      72.2%, p < 0.01) and inferior overall survival (20.61 vs. 29.74 months,
      cumulative survival 45.2% vs. 79.3%, p < 0.001) than low MIF expressers.
      Multivariate cox-regression analysis adjustment confirmed that high MIF
      expression was the only independent prognostic factor in ALL patients for OS and
      DFS in our study (p = 0.004, p = 0.01 respectively). CONCLUSIONS: We found that
      MIF expression is an important prognostic factor in ALL patients with normal
      karyotype, and its incorporation into novel risk-adapted therapeutic strategies
      will improve the current cure rates for this group of patients.

PMID- 30274022
TI  - Boronate Affinity Chromatography Accurately Measures HbA1c also in Patients with
      End-Stage Renal Disease - Performance Evaluation of the A1c HPLC Analyzer.
AB  - BACKGROUND: Boronate affinity chromatography is widely used, and the method has
      lately been improved and designed for HbA1c measurements. We report performance
      evaluation of the affinity chromatography HbA1c HPLC analyzer. METHODS: Within-
      and between-run imprecision was assessed based on the results of a series of
      measurements in three different EDTA blood samples and in control materials.
      HbA1c levels were measured and compared in 349 EDTA blood samples and 50 samples
      from patients with end-stage renal disease (ESRD) using the Premier Hb9210
      analyzer (affinity chromatography) and the D-10 Hemoglobin Testing System (ion
      exchange chromatography). RESULTS: The within- and between-run imprecision CVs
      ranged from 0.72% to 2.01%. Median HbA1c level measured by the Premier Hb9210 was
      significantly lower (6.4% [46 mmol/mol] vs. 6.6% [49 mmol/mol], p < 0.001). The
      Passing-Bablok agreement test yielded a slope of 1.0 (95% CI: 1.0 to 1.0) and
      intercept of -0.1 (95% CI: -0.1 to -0.1). Correlation coefficient and the mean
      difference amounted to 0.992 and -0.13% (95% CI: -0.11 to -0.15), respectively.
      Similar results were obtained for HbA1c levels < 7% [< 53 mmol/mol] and >= 7% [>=
      53 mmol/mol]. In ESRD patients, median HbA1c level measured by the Premier Hb9210
      was also significantly lower (6.0% [42 mmol/mol] vs. 6.5 [48 mmol/mol], p <
      0.001) with the mean difference equal to -0.52% (95% CI: -0.59 to -0.46).
      CONCLUSIONS: Although the Premier Hb9210 gave lower HbA1c levels, good results
      agreement with the D-10 Hemoglobin Testing System was found. Analytical
      performance found for HbA1c measurements in ESRD patients was similar. The
      Premier Hb9210 analyzer is suitable for routine HbA1c testing in clinical
      practice.

PMID- 30274021
TI  - Effect of Maternal and Neonatal Factors on Neonatal Thyroid Screening Results.
AB  - BACKGROUND: Thyroid-stimulating hormone (TSH) levels are an important parameter
      in screening for congenital hypothyroidism (CH). This study aimed to analyze the
      effects of birth weight, gestational age, and delivery mode on the incidence of
      neonatal CH. METHODS: A retrospective cohort study of neonates born in 2015 at a
      maternity hospital in Xiamen, China and their mothers was conducted. Differences
      in TSH levels, CH positivity at baseline, and the incidence of CH according to
      gestational age, birth weight, and delivery mode were assessed using matched
      neonatal and maternal data. RESULTS: Of the 15,615 enrolled neonates, 150 had
      positive CH screening results at baseline and nine had confirmed CH. Premature
      and low-birth-weight neonates had a significantly higher incidence of CH and
      lower TSH levels when compared to full-term neonates and normal-to-high birth
      weight neonates, respectively. Neonates delivered vaginally had significantly
      lower TSH levels and a reduced incidence of baseline CH positivity; cesarean
      section delivery (odds ratio [OR] = 2.06, p = 0.006) and a maternal TSH level
      >2.5 mIU/L (OR = 2.37, p = 0.002) were risk factors for CH positivity at
      baseline. CONCLUSIONS: In this study, the incidence of CH in neonates was
      associated with gestational age and birth weight. Neonatal baseline CH positivity
      was positively associated with cesarean delivery and an early-pregnancy maternal
      TSH level >2.5 mIU/L.

PMID- 30274024
TI  - Genome-Wide Analysis of mRNA Expression Profiling Identified Lung Cancer-Related
      Gene in Xuanwei, China.
AB  - BACKGROUND: The morbidity and mortality of lung cancer in Xuanwei (LCXW) is among
      the highest in China for both males and females and increases constantly. The
      underlying molecular changes associated with LCXW are still unclear. The purpose
      of this study was to screen out potential cancer-related genes which may become
      promising biomarkers of LCXW. METHODS: Differentially expressed genes (DEGs) were
      detected by the expression microarrays in 29 paired LCXW tissues (tumor tissue
      and matched adjacent non-cancerous lung tissues). Integrated with bioinformatic
      analyses, a literature review was applied for screening out important cancer
      related genes. An additional 44 paired LCXW samples were collected to verify the
      transcription and expression levels of the candidate gene by qRT-PCR and Western
      blotting. The relationship between the candidate genes and clinical pathological
      features were evaluated using Fisher's test. RESULTS: mRNA expression microarrays
      revealed that the LCXW patients harbored 2,424 differentially expressed genes
      (fold change >= 2.0). Of these genes, 1,636 were up-regulated while the other 788
      genes were down-regulated. Forty previously reported DNA repair genes associated
      with PAHs exposure were identified by microarrays. Bioinformatic analyses
      indicated down-regulated ANXA3 in LCXW patients which was closely related to
      pathological stage and involved in the regulation of a variety of biological
      responses. Review of the literature on ANXA3 found its down-regulation was a
      distinct expression pattern compared with lung cancer occurring in other
      geographic areas. qRT-PCR and Western blotting confirmed the down-regulation of
      ANXA3 was associated with LCXW. The correlation analysis of clinical features
      showed down-regulated ANXA3 was correlated to the progression of pathological
      stage. CONCLUSIONS: The LCXW patients harbored more DEGs, and these DEGs were
      involved in a wide range of pathways and biological function damage. We
      preliminarily suggested ANXA3 may be a potential LCXW related gene. ANXA3 may
      serve as a promising biomarker for diagnosis of LCXW.

PMID- 30274023
TI  - Results of Laboratory Tests not Accessed in Brazilian Private Laboratories.
AB  - BACKGROUND: Laboratory medicine is an important part of the healthcare system and
      directly contributes to preventive actions, diagnostics, treatment, and
      management of diseases. The level and quality of the utilization of laboratory
      resources have been frequently questioned. A dissemination of conflicting data
      regarding the quantity of laboratory tests not accessed by the requesting doctors
      or by the patients themselves is observed, although very often the sources and
      methodologies used to raise those numbers are not properly clarified. The
      objective of this study was to obtain data about access to results of tests taken
      in Brazilian private clinical analysis laboratories which use the laboratory
      information system developed by SHIFT Consultoria e Sistemas. METHODS:
      Information was extracted from 81 laboratories, which were responsible for the
      performance of 93,240,651 tests, collected from 7,067,087 patients. RESULTS: The
      total number of tests not accessed, considering all the regions, was 5,071,454,
      corresponding to a proportion of 5.4%. In the face of the potential risks of
      adverse events or impacts in the management of diagnostics and treatments,
      including economic impacts due to prolonged hospitalization time, the proportion
      of 17.9% which was found corresponding to tests "not accessed" showing "abnormal"
      results, is worrisome, mainly if we observe that of those, 2.5% were related to
      "abnormal" test results processed by laboratories which work in hospital care.
      CONCLUSIONS: SBPC/ML, in face of the relevance of the theme, will keep
      stimulating the monitoring and utilization of adequate laboratory resources, in
      order to allow sustainable healthcare systems.

PMID- 30274025
TI  - Expression of Plasma miRNA-221 in Colorectal Carcinoma Patients and its
      Diagnostic Significance in Comparison with p53 Expression.
AB  - BACKGROUND: Colorectal carcinoma development progresses through a sequence of
      normal mucosa-polyp-carcinoma. Early detection of premalignancy is crucial for
      improved outcomes. We evaluated the diagnostic performance of plasma miRNA-221
      and its feasibility in discriminating premalignant from malignant neoplasms and
      correlating it with immunohistochemical p53 expression. METHODS: A total of 109
      plasma samples were collected (76 carcinoma, 14 premalignant, and 19 controls).
      MiRNA221 was quantified by qPCR for calculation of ?Ct using RNU6B as endogenous
      control. p53 immunohistochemical staining was performed on corresponding tissue.
      RESULTS: Plasma miRNA-221 and p53 in tissues were significantly overexpressed in
      the malignant group when compared with the premalignant and control groups.
      Plasma miRNA-221 was increased in late-stage tumors with nodal or distant
      metastasis. ROC curve construction for distinguishing between malignant and
      premalignant tumors revealed a cutoff value of 2.97 with 74% sensitivity, 79%
      specificity, 73.7% positive predictive value and 78.6% negative predictive value
      (AUC = 0.824; p = 0.001). Plasma miRNA-221 significantly correlated with p53 in
      cancer samples (r = 0.507). CONCLUSIONS: MiRNA-221 could have a diagnostic role
      in differentiating malignant from premalignant neoplasms and could also serve as
      a predictive marker indicating tumor progression.

PMID- 30274026
TI  - Chimerism Monitoring by Short Tandem Repeat (STR) Markers in Allogeneic Stem Cell
      Transplantation.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell (allo-HSC) transplantation is used
      in the treatment of malignant hematological diseases. An important tool in
      monitoring post-transplantation evolution is represented by the percentage of
      donor's blood cells found in recipient's blood, known as chimersim. This is
      useful in predicting the graft rejection and the risk of disease relapse. In this
      study, we present the importance of multiplex STR markers in chimerism monitoring
      of a 8 year old girl diagnosed with acute lymphoblastic leukemia (ALL). METHODS:
      In the pre-transplant stage, saliva on buccal swabs and blood samples in EDTA
      were collected from the donor and recipient and used as reference samples. The
      DNA extraction from saliva and blood samples was done using the Pure Link Genomic
      DNA kit (Invitrogen, USA). For the DNA quantification, the Quantifiler Human DNA
      kit (Applied Biosystems, USA) was used on an ABI 7500 Real-time PCR system
      (Applied Biosystems, USA). Amplification of the STR markers was performed using
      the AmpFLSTR NGM SElect kit (Applied Biosystems, USA) on a ProFlex PCR System.
      The PCR products were separated and detected on an ABI 3500 Genetic Analyzer
      (Applied Biosytems, USA). RESULTS: One month post-transplantation of HSC, a mixed
      chimerism (MC) containing 38% of donor's cells was obtained from a bone marrow
      aspiration sample. On the 45th day, a new transplantation was performed. On the
      15th day after 2nd transplantation, a MC with 91% donor's cells was obtained. On
      the 21st day after the 2nd transplantation, a complete chimerism (CC) with 100%
      donor's cells was obtained. CONCLUSIONS: Chimerism monitoring is useful in
      identifying those patients in risk for relapse or graft rejection.

PMID- 30274027
TI  - Clinical Laboratory - Protagonist in Patient Safety.

PMID- 30274028
TI  - Relationship Among Antibiotic Resistance, Biofilm Formation and lasB Gene in
      Pseudomonas Aeruginosa Isolated from Burn Patients.
AB  - BACKGROUND: Pseudomonas aeruginosa is a major cause of hospital-acquired
      infection due to its high antibiotic resistance and biofilm formation ability. P.
      aeruginosa produces elastase lasB during biofilm formation, which can influence
      properties of biofilm. This study was carried out to evaluate the antibiotic
      resistance and distribution of the lasB gene among biofilm-producing P.
      aeruginosa strains isolated from burn patients. METHODS: A total of 128 clinical
      samples were collected from burn patients. The P. aeruginosa isolates were
      identified using standard bacteriological procedures. Antibiotic susceptibility
      test was performed by the disk diffusion method. Biofilm formation was measured
      by microtiter plate assay. The presence of lasB gene was detected by PCR.
      RESULTS: A total of 75 samples were positive for P. aeruginosa. A high rate of
      resistance was seen against ceftriaxone, cefotaxime, and piperacillin/tazobactam.
      Biofilm formation was seen in 57.3% of the isolates and the prevalence of the
      lasB gene was 85.3%. Biofilm formation in isolates without lasB was lower and
      these isolates were more sensitive to imipenem and piperacillin/tazobactam.
      CONCLUSIONS: In the present study, we did not find a statistically significant
      relationship among elastase gene (lasB) presence, antibiotic resistance, and
      biofilm formation in P. aeruginosa strains isolated from burn patients.

PMID- 30274029
TI  - A Single Step Mutation at D3S1358 Locus in a DNA Paternity Testing with 2 Alleged
      Fathers.
AB  - BACKGROUND: Genetic information is used very frequently in human identification
      in civil or judicial cases. Establishing the kinship relationship between a child
      and his biological father involves many ethical facts. We describe a DNA
      paternity case with two alleged fathers and an inconsistency between alleged
      father-2 and the child at D3S1358 locus. METHODS: As biological samples we used
      saliva collected from inside the cheek of each person using buccal swabs (Copan,
      Italy). We collected the biological samples from each of person after each person
      gave the consent. In order to find the concentration of salivary DNA, the DNA
      samples were quantified by 7500 ABI Real-time PCR using the Quantifiler Human DNA
      kit (Applied Biosystems, USA). The next step was the amplification of the
      Salivary DNA samples by polymerase chain reaction (PCR). It was performed on a
      ProFlex PCR System (Applied Biosystems, USA) using the multiplex STR markers from
      the AmpFlSTR(r) Identifiler Plus Amplification Kit (Applied Biosystems, USA).
      After amplification, the PCR products were run on capillary electrophoresis on an
      ABI 3500 Genetic Analyzer (Applied Biosystems, USA). RESULTS: AF-1 was excluded
      as biological father. The DNA profiles of AF-2 and the child had one mismatch at
      D3S1358 locus. Further, we amplified the Y-STR markers to confirm the mutation,
      obtaining a perfect match between the 2 persons. CONCLUSIONS: In paternity
      testing, where one or two inconsistencies are present between the child and the
      alleged father on autosomal STR markers, the use of haploid markers X-STR or Y
      STRs is needed for the confirmation or exclusion of paternity.

PMID- 30274030
TI  - Novel polysaccharide hybrid scaffold loaded with hydroxyapatite: Fabrication,
      bioactivity, and in vivo study.
AB  - The main goal of this study was to produce a novel porous scaffold for rapid in
      vivo bone healing behavior. Lyophilization technique was used to produce this
      highly porous hybrid scaffold from Na-alginate (S) and hydroxyethylcellulose
      (HEC) impregnated with different concentration of hydroxyapatite (HA). After
      cross-linking the scaffolds, their incubation was carried out in simulated body
      fluid (SBF) for 4 weeks at 37  degrees C to investigate their bioactivity. A
      number of techniques were employed (e.g., XRD, FTIR, SEM, EDX, and texture
      analyzer) to characterize the designed scaffolds. It was observed that the
      mechanical properties of the scaffolds increase deformation energy (182 +/- 16
      J/m3) and rigidity gradient (19.44 +/- 0.85 Pa) after loading with HA.
      Furthermore, the scaffolds were implanted in femur critical size defects (2 mm)
      of adult male Wistar rats for 6 weeks. In vitro and in vivo analyses demonstrated
      impressive bioactivity and biocompatibility for the prepared scaffolds,
      especially those containing HA. Based on the obtained results we conclude that
      the designed scaffolds are promising solutions for bone regeneration
      applications.

PMID- 30274031
TI  - Photostable, hydrophilic, and near infrared quaterrylene-based dyes for
      photoacoustic imaging.
AB  - Novel near-infrared contrast agents based on the quaterrylene structure were
      strategically developed and tested for high photo-stability. Both a dendrimeric
      quaterrylene molecule, QR-G2-COOH, and a small molecule cationic quaterrylene
      dye, QR-4PyC4, remain optically stable and continue to generate a competitive
      photoacoustic response when irradiated by short near-infrared laser pulses for a
      relatively long time in an in-vitro cell study, unlike indocyanine green that
      rapidly decreases photoacoustic signal amplitude. The small molecule dye, QR
      4PyC4 exhibits not only significantly higher cellular uptake rate than QR-G2-COOH
      and indocyanine green, but also low toxicity at a concentration of up to 10 MUM.
      The dendrimeric dye, QR-G2-COOH that has surface functional groups available for
      conjugation with targeting and therapeutic agents shows the highest photoacoustic
      amplitude with high optical stability. Therefore, QR-4PyC4 can be a promising
      universal, sensitive and reliable photoacoustic contrast agent and QR-G2-COOH has
      great potential as a nano-platform with stable photoacoustic imaging capability.

PMID- 30274033
TI  - The controllable lanthanum ion release from Ca-P coating fabricated by laser
      cladding and its effect on osteoclast precursors.
AB  - Several studies have suggested that rare earth oxides can improve properties of
      bioceramic coating, and bone resorption of osteoclast can be inhibited by rare
      earth ion releasing certain concentration. However, the effects of lanthanum ion
      (La3+) released from Ca-P coating on osteoclast precursors is not clear. In this
      work, La2O3-doped gradient bioceramic coatings were fabricated on Ti alloy (Ti
      6Al-4V) by laser cladding with mixed powders of CaHPO4.2H2O, CaCO3 and La2O3. And
      the bioactivity, mechanical properties and the La3+ release from coating were
      investigated in vitro. Human osteosarcoma cells (MG63) were used as a cell model
      to evaluate the biocompatibility of coatings. Mouse macrophage RAW264.7 cells
      were cultured on coatings to study the effect of La3+ release from Ca-P coating
      on osteoclast precursors. The XRD results reveal that the amount of HA + TCP
      reaches maximum (2theta = 32-33 degrees ) when the content of La2O3 is 0.6 wt%,
      and the proliferation of MG63 cells is up to highest value, which indicates that
      compared with other groups, the bioceramic coating with 0.6 wt% La2O3 is of best
      biocompatibility. Furthermore, the differentiation of RAW264.7 cells into
      osteoclast could be inhibited by controllable releasing La3+ from Ca-P coating
      when soaked in SBF, which demonstrates that controllable La3+ release from Ca-P
      coating is an effective method to prevent osteoclast formation. And a prospective
      therapy is provided to cure the disease of wear debris in replacement of
      artificial joint.

PMID- 30274032
TI  - Durability of self-healing dental composites: A comparison of performance under
      monotonic and cyclic loading.
AB  - : Durability is an important quality of dental restorative materials, and the
      ability to autonomously heal damage incurred during their oral function is highly
      desirable. OBJECTIVE: The objective was to evaluate the improvement in durability
      of self-healing dental composites (SHDCs) in terms of their resistance to
      fracture and capacity for healing of damage under monotonic and cyclic loading.
      METHODS: SHDCs were prepared by incorporating dental resin composites with
      microcapsules containing healing liquid. Control specimens with the same mass
      fraction (5% and 25%) of microcapsules filled with water were also evaluated. Two
      sets of SHDCs were distinguished by the silane coupling agents that
      functionalized and bonded the microcapsules to resin network. One set used a
      methacrylate silane (MA-silane) that connected resin network through covalent
      bonds, and the other used a H-bonding forming hydroxyl silane (OH-silane). The
      fatigue crack growth resistance was assessed in terms of the threshold stress
      intensity range and the conventional Paris Law parameters. Cyclic loading was
      conducted at 5 Hz with maximum cyclic load ranged between approximately 1 N and 5
      N. The efficiency of the autonomous healing was determined per the recovering of
      the fracture toughness and the extension of fatigue life. RESULTS: The SHDCs with
      5 wt% of healing microcapsules exhibited a larger fracture toughness than those
      with 25 wt% microcapsules. MA-silane SHDCs had approximately five times more
      responsive microcapsules triggered by fracturing of the composites. Consequently,
      the MA-silane SHDCs with 5 wt% of microcapsules achieved the best performance in
      terms of fracture toughness and healing efficiency. In regards to the fatigue
      crack growth behavior, there was a significant increase in the resistance to
      fatigue crack growth and 580 +/- 15% improvement in the fatigue life.
      SIGNIFICANCE: Strong silanization is vital in SHDCs to simultaneously achieve
      clinically applicable mechanical performance and substantial healing capability.
      Moreover, the evaluation of self-healing under cyclic loading is a promising tool
      in quantifying the degree of fracture-induced healing.

PMID- 30274034
TI  - Assessment of novel core-shell Fe3O4@poly l-DOPA nanoparticles for targeted
      Taxol(r) delivery to breast tumor in a mouse model.
AB  - Drug delivery systems using nanoparticles can deliver to tumor cells without
      affecting normal cells. In this study, a novel well dispersed magnetic nano drug
      was synthesized. Thus, a selective drug delivery system was designed for
      potential cancer treatment. A new nanocomposite, poly 3,4-dihydroxy-l
      phenylalanine/Fe3O4 (l-DOPA/Fe3O4), was synthesized and used for targeted
      Taxol(r) delivery to breast tumor in inbreed Balb/c mice model with or without
      magnetic field. Fe and Taxol(r) concentrations were measured by flame atomic
      absorption spectrometry and high-performance liquid chromatography, respectively.
      Antitumor effectiveness was investigated in terms of tumor growth features. In
      the presence of magnetic field, Taxol(r) was significantly deposited in tumor
      tissue in Taxol-nanocomposite-treated group. In addition, the Taxol(r)
      nanocomposite-treated group with magnetic field showed higher antitumor efficacy
      than the commercial Taxol and Taxol-nanocomposite without magnetic field. The
      magnetic nanocomposite is promising for targeted Taxol(r) delivery to breast
      tumor in a mouse model yielding high performance.

PMID- 30274035
TI  - "Green-reduced" graphene oxide induces in vitro an enhanced biomimetic
      mineralization of polycaprolactone electrospun meshes.
AB  - A novel green method for graphene oxide (GO) reduction via ascorbic acid has been
      adopted to realize bio-friendly reduced graphene oxide (RGO)/polycaprolactone
      (PCL) nanofibrous meshes, as substrates for bone tissue engineering applications.
      PCL fibrous mats enriched with either RGO or GO (0.25 wt%) were fabricated to
      recapitulate the fibrillar structure of the bone extracellular matrix (ECM) and
      the effects of RGO incorporation on the structural proprieties, biomechanics and
      bioactivity of the nano-composites meshes were evaluated. RGO/PCL fibrous meshes
      displayed superior mechanical properties (i.e. Young's Modulus and ultimate
      tensile strength) besides supporting noticeably improved cell adhesion, spreading
      and proliferation of fibroblasts and osteoblast-like cell lines. Furthermore, RGO
      based electrospun substrates enhanced in vitro calcium deposition in the ECM
      produced by osteoblast-like cells, which was paralleled, in human mesenchymal
      stem cells grown onto the same substrates, by an increased expression of the
      osteogenic markers mandatory for mineralization. In this respect, the capability
      of graphene-based materials to adsorb osteogenic factors cooperates synergically
      with the rougher surface of RGO/PCL-based materials, evidenced by AFM analysis,
      to ignite mineralization of the neodeposited matrix and to promote the osteogenic
      commitment of the cultured cell in the surrounding microenvironment.

PMID- 30274036
TI  - Red, green, and blue fluorescent folate-receptor-targeting carbon dots for
      cervical cancer cellular and tissue imaging.
AB  - Folate receptor targeted photo-luminescent quantum carbon dots (Fr-CDs) were
      successfully prepared from folic acid and phenylenediamine isomers through
      hydrothermal approaches. Fr-CDs were spherical particles smaller than 10 nm, and
      emit stable green, blue and red luminescence under ultraviolet region excitation
      (lambdaex = 365 nm) with maximum emissive lengths at 530, 429, and 612 nm. And
      the corresponding photoluminescence quantum yield as 15.4%, 12.6% and 16.2%
      respectively. Up-converted photoluminescent properties in near infrared 800 nm
      spectral region located in green, blue and yellow region. In-vitro studies showed
      Fr-CDs had almost none cytotoxicity (cell viability over 80%) and high affinitive
      to the Hela celline highly-expressed-folate-receptor membranes, and lighted on
      cytoplasm as the fluorescent marker. It displayed long luminescent-stability with
      PL intensity above 90% in ultraviolet illuminant exposure over 24 h. In in-vivo
      studies, Fr-CDs were internalized and accumulated in targeted cancer tissues of
      cervical carcinoma and the emitting fluorescence maintains over 30 min.

PMID- 30274037
TI  - Promotion of chondrogenic differentiation of mesenchymal stem cells by copper:
      Implications for new cartilage repair biomaterials.
AB  - Copper (Cu) has drawn considerable attention in the design of biomaterials due to
      its multifunction, such as antibacterial property, osteogenic and angiogenic
      ability. However, the effect of Cu on chondrogenic differentiation of mesenchymal
      stem cells (MSCs) and its potential for cartilage repair biomaterials has been
      rarely studied. Here, we report that Cu can significantly enhance chondrogensis
      of MSCs. Specifically, in vitro studies showed that Cu could promote MSCs
      cytoskeleton change, extracellular glycosaminoglycan (GAG) deposition and the
      chrodrogenic genes (Sox9, Aggrecan, and Col-2) up-regulation. Furthermore, we
      prepared a Cu-containing alginate (Alg) porous scaffold to assess the
      chondroinductivity of Cu in vivo. In eight weeks, we found that Alg/Cu scaffolds
      could induce better formation of new cartilage tissue compared to the pure Alg
      scaffolds fabricated by the same procedure but without adding Cu. These
      encouraging results indicate that Cu can bring considerable benefits to the
      development and application of cartilage repair biomaterials.

PMID- 30274038
TI  - Dynamic imine bond cross-linked self-healing thermosensitive hydrogels for
      sustained anticancer therapy via intratumoral injection.
AB  - In this study, we developed a self-healing thermosensitive gel, via dialdehyde
      functionalized polyethylene glycol (DF-PEG) and beta-glycerophosphate (GP) cross
      linked chitosan (CS) hydrogels, which enable autonomous self-healing upon damage
      and sustained release of doxorubicin hydrochloride (DOX) for antitumor therapy
      via intratumoral injection. The cross-linked gels could exhibit sol-gel
      transition at 37  degrees C within 5 min and satisfactory in vitro and in vivo
      healing ability by observing the rejoining and fusion process of scratched gels.
      Moreover, the in vitro release of DOX loaded cross-linked gels in PBS (pH 6.5 and
      7.4) was found to be extended to 13 d. After intratumoral injection in Heps tumor
      bearing mice, the drug loaded self-healing thermosensitive gels showed a superior
      tumor inhibition rate (66.12%) than CS thermosensitive hydrogels (53.23%), while
      the histology studies gave the relieved cardiotoxicity and good biocompatibility
      of the cross-linked gels. Overall, these cross-linked gels could become a
      potential local drug delivery system to achieve efficient sustained release,
      relieved side effects and enhanced therapy efficiency through localized
      administration.

PMID- 30274039
TI  - Surface modification of stainless steel for biomedical applications: Revisiting a
      century-old material.
AB  - : Stainless steel (SS) has been widely used as a material for fabricating
      cardiovascular stents/valves, orthopedic prosthesis, and other devices and
      implants used in biomedicine due to its malleability and resistance to corrosion
      and fatigue. Despite its good mechanical properties, SS (as other metals) lacks
      biofunctionality. To be successfully used as a biomaterial, SS must be made
      resistant to the biological environment by increasing its anti-fouling
      properties, preventing biofilm formation (passive surface modification), and
      imparting functionality for eluting a specific drug or capturing selected cells
      (active surface modification); these features depend on the final application.
      Various physico-chemical techniques, including plasma vapor deposition,
      electrochemical treatment, and attachment of different linkers that add
      functional groups, are used to obtain SS with increased corrosion resistance,
      improved osseointegration capabilities, added hemocompatibility, and enhanced
      antibacterial properties. Existing literature on this topic is extensive and has
      not been covered in an integrated way in previous reviews. This review aims to
      fill this gap, by surveying the literature on SS surface modification methods, as
      well as modification routes tailored for specific biomedical applications.
      STATEMENT OF SIGNIFICANCE: Stainless steel (SS) is widely used in many biomedical
      applications including bone implants and cardiovascular stents due to its good
      mechanical properties, biocompatibility and low price. Surface modification
      allows improving its characteristics without compromising its important bulk
      properties. SS with improved blood compatibility (blood contacting implants),
      enhanced ability to resist bacterial infection (long-term devices), better
      integration with a tissue (bone implants) are examples of successful SS surface
      modifications. Existing literature on this topic is extensive and has not been
      covered in an integrated way in previous reviews. This review paper aims to fill
      this gap, by surveying the literature on SS surface modification methods, as well
      as to provide guidance for selecting appropriate modification routes tailored for
      specific biomedical applications.

PMID- 30274040
TI  - Exploring inhalable polymeric dry powders for anti-tuberculosis drug delivery.
AB  - The growing interest on polymeric delivery systems for pulmonary administration
      of drugs anticipates a more direct and efficient treatment of diseases such as
      tuberculosis (TB) that uses the pulmonary route as the natural route of
      infection. Polymeric microparticles or nano-in-microparticles offer target
      delivery of drugs to the lungs and the potential to control and sustain drug
      release within TB infected macrophages improving the efficiency of the anti-TB
      treatment and reducing side effects. In a dry powder form these inhalable
      delivery systems have increased stability and prolonged storage time without
      requiring refrigeration, besides being cost-effective and patient convenient.
      Thus, this review aims to compile the recent innovations of inhalable polymeric
      dry powder systems for the delivery of anti-TB drugs exploring the methods of
      production, aerodynamic characterization and the efficacy of targeted drug
      delivery systems using in vitro and in vivo models of the disease. Advanced
      knowledge and promising outcomes of these systems are anticipated to simplify and
      revolutionize the pulmonary drug delivery and to contribute towards more
      effective anti-TB treatments.

PMID- 30274041
TI  - Recent exploration of bio-mimetic nanomaterial for potential biomedical
      applications.
AB  - Bio-inspired materials with the multiscale skeleton show intrinsic
      multifunctional integration. This special biological characteristic is designed
      and developed to encourage scientists and engineers to multiobjective artificial
      physicals with multiscale frameworks. This review focuses on some recent
      development in the areas of classical biomaterials including lotus leaves,
      butterfly wings, red rose petals, spider silks and the associated multiscale
      frameworks acquiring function coalescence. We have also addressed some queries
      and standpoints for bio-inspired form of drug delivery using pathogens, which
      sheds light on delivery of proteins, small interfering RNA and other therapeutic
      agents.

PMID- 30274042
TI  - Tissue mimicking materials in image-guided needle-based interventions: A review.
AB  - Image-guided interventions are widely employed in clinical medicine, which brings
      significant revolution in healthcare in recent years. However, it is impossible
      for medical trainees to experience the image-guided interventions physically in
      patients due to the lack of certificated skills. Therefore, training phantoms,
      which are normally tissue mimicking materials, are widely used in medical
      research, training, and quality assurance. This review focuses on the tissue
      mimicking materials used in image-guided needle-based interventions. In this
      case, we need to investigate the microstructure characteristics and mechanical
      properties (for needle intervention), optical properties and acoustical
      properties (for imaging) of these training phantoms to compare with the related
      properties of human real tissues. The widely used base materials, additives and
      the corresponding concentrations of the training phantoms are summarized from the
      literatures in recent ten years. The microstructure characteristics, mechanical
      behavior, optical properties and acoustical properties of the tissue mimicking
      materials are investigated, accompanied with the common experimental methods,
      apparatus and theoretical algorithm. The influence of the concentrations of the
      base materials and additives on these characteristics are compared and
      classified. In this review, we assess a comprehensive overview of the existing
      techniques with the main accomplishments, and limitations as well as
      recommendations for tissue mimicking materials used in image-guided needle-based
      interventions.

PMID- 30274043
TI  - In vitro evaluation of a biomaterial-based anticancer drug delivery system as an
      alternative to conventional post-surgery bone cancer treatment.
AB  - Patients diagnosed with osteosarcoma are currently treated with intravenous
      injections of anticancer agents after tumor resection. However, due to remaining
      neoplastic cells at the site of tumor removal, cancer recurrence often occurs.
      Successful bone regeneration combined with the control of residual cancer cells
      presents a challenge for tissue engineering. Cyclodextrins loaded with
      chemotherapeutic drugs reversibly release the drugs over time. Hydroxyapatite
      bone biomaterials coated with doxorubicin-loaded cyclodextrin should release the
      drug with time after implantation directly at the original tumor site and may be
      a way to eliminate residual neoplastic cells. In the present study, we have
      carried out in vitro studies to evaluate such a drug-delivery system and have
      shown that doxorubicin released from cyclodextrin-coated hydroxyapatite retained
      biological activity and exhibited longer and higher cytotoxic effects on both
      cancer (osteosarcoma cells) and healthy cells (primary osteoblasts and
      endothelial cells) compared to biomaterials without cyclodextrin loaded with
      doxorubicin. Furthermore, doxorubicin released from biomaterials with
      cyclodextrin moderately induced the expression of tumor suppressor protein p53
      whereas p21 expression was similar to control cells. In addition, hypoxic
      conditions, which occur after implantation until blood-flow to the area is
      regenerated, protected endothelial cells and primary osteoblasts from doxorubicin
      induced cytotoxicity. This chemo-protective effect was far less prominent for the
      osteosarcoma cells. These findings indicate that a hydroxyapatite-cyclodextrin
      doxorubicin chemotherapeutic strategy may enhance the drug-targeting effect on
      tumor cells while protecting the more sensitive healthy cells for a period of
      time after implantation. A successful integration of such a drug delivery system
      might allow healthy cells to initially survive during the doxorubicin exposure
      period, while eliminating residual neoplastic cells.

PMID- 30274044
TI  - Hierarchical structures on nickel-titanium fabricated by ultrasonic nanocrystal
      surface modification.
AB  - Hierarchical structures on metallic implants can enhance the interaction between
      cells and implants and thus increase their biocompatibility. However, it is
      difficult to directly fabricate hierarchical structures on metallic implants. In
      this study, we used a simple one-step method, ultrasonic nanocrystal surface
      modification (UNSM), to fabricate hierarchical surface structures on a nickel
      titanium (NiTi) alloy. During UNSM, a tungsten carbide ball hits metal surfaces
      at ultrasonic frequency. The overlapping of the ultrasonic strikes generates
      hierarchical structures with microscale grooves and embedded nanoscale wrinkles.
      Cell culture experiments showed that cells adhere better and grow more
      prolifically on the UNSM-treated samples. Compared with the untreated samples,
      the UNSM-treated samples have higher corrosion resistance. In addition, the
      surface hardness increased from 243 Hv to 296 Hv and the scratch hardness
      increased by 22%. Overall, the improved biocompatibility, higher corrosion
      resistance, and enhanced mechanical properties demonstrate that UNSM is a simple
      and effective method to process metallic implant materials.

PMID- 30274045
TI  - Molecular encapsulator-appended poly(vinyl alcohol) shroud on ferrite
      nanoparticles. Augmented cancer-drug loading and anticancer property.
AB  - Magnetic nanoparticles (MNPs) have the potency to deliver cancer drugs assisted
      by the application of a magnetic field. In this paper, we present the design of
      magnesium ferrite nanoparticles of size suitable for drug delivery. A coating
      polymer, poly(vinyl alcohol), tethered with a tapered cone-shaped cyclic
      oligosachcharide, beta-cyclodextrin (beta-CD) is synthesized and used to wrap and
      disperse the MNPs. The magnetic properties are explored using vibrating sample
      magnetometry and Mossbauer spectroscopy. The ?130 nm MNPs, shrouded with the PVA
      CD conjugate allows a high amount of the cancer drug, camptothecin, to be loaded
      on the nanocarrier. Cytotoxicity studies reveal that the loaded drug retains its
      potency against HEK 293 cells and the cells are sensitive to the treatment by the
      drug-loaded nanocarrier.

PMID- 30274046
TI  - Lecithin suspensions for electrophoretic deposition on stainless steel coatings.
AB  - Lecithin is a mixture of phospholipids (PLs) that are found in living organisms.
      It gained the interest as a bio- and hemocompatible modifying agent for
      biomaterials. In this paper, we focused on the elaboration of a simple and well
      described technology of metals coating with low-cost substance that could be
      useful in biomaterials industry. We studied the utility of lecithin suspension
      for stainless steel coating by electrophoretic deposition method. Our goal was to
      find a relationship between the conditions of lecithin suspension preparation,
      obtained suspension properties (vesicles size and structure, zeta potential,
      electrophoretic mobility) and lecithin coating features (topography, roughness).
      We found that final pH value, zeta potential and electrophoretic mobility of
      lecithin suspensions were not altered by initial solution pH value. However, the
      presence of hydrated Na+ ions forced forming of large multi-layered vesicles. We
      obtained uniform lecithin coatings with the use of electrophoretic deposition,
      which has a great potential to be used in a large scale.

PMID- 30274047
TI  - Electrochemical immunosensor based on magnetite nanoparticles incorporated
      electrospun polyacrylonitrile nanofibers for Vitamin-D3 detection.
AB  - In the present study, magnetite nanoparticles (Fe3O4 NPs) incorporated
      polyacrylonitrile nanofibers (PANnFs) having diameter of 350-500 nm, were
      electrospun and directly collected onto indium tin oxide (ITO) coated glass
      substrate. X-ray diffraction pattern of Fe3O4-PANnFs confirmed the existence of
      Fe3O4 NPs within the PANnFs. Nafion was used to make Fe3O4-PANnFs more adhesive
      to the ITO surface. Partial hydrolyzation of Fe3O4-PANnFs/ITO electrode was done
      using NaOH solution for the partial conversion of nitrile group (C=N) into
      carboxyl and amine groups that was confirmed by Fourier transform infrared
      spectroscopy study. The hydrolyzed Fe3O4-PANnFs/ITO electrode was used as an
      immobilization matrix for monoclonal antibody specific to Vitamin-D3 (Anti-VD)
      via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-Hydroxysuccinimide
      chemistry. Bovine serum albumin (BSA) was used as a blocking agent to block the
      non-specific sites onto Anti-VD/Fe3O4-PANnFs/ITO electrode surface. Fabricated
      BSA/Anti-VD/Fe3O4-PANnFs/ITO immunoelectrode showed improved biosensing
      parameters for Vitamin-D3 detection such as sensitivity of 0.90 MUA ng-1 mL cm-2,
      limit of detection of 0.12 ng mL-1and detection range of 10-100 ng mL-1. The
      association and dissociation constants were obtained as 74.62 ng mL-1, 4.6 ng mL
      1, respectively.

PMID- 30274048
TI  - Synergistic effect of co-immobilized FGF-2 and vitronectin-derived peptide on
      feeder-free expansion of induced pluripotent stem cells.
AB  - Expansion of human induced pluripotent stem cells (h-iPSCs) on mouse derived
      feeder layers or murine cells secretions such as Matrigel hamper their clinical
      applications. Alternative methods have introduced novel substrates as stem cell
      niches or/and optimized combinations of humanized soluble factors as fully
      defined mediums. Accordingly vitronectin as a main part of ECM have been
      commercialized significantly as a stem cell niche-forming substrate. In this
      work, we used a functional peptide derived from vitronectin (VTN) and co
      immobilized it with FGF-2 (as an indisputable ingredient of defined culture
      mediums) on chitosan film surface. After chemical and physical characterization
      of the pristine chitosan surface as well as ones modified by VTN or/and FGF-2, h
      iPS cells were cultured on them at the xeno/feeder-free conditions. Our results
      demonstrated that co-immobilization of these two biomolecules has a synergistic
      effect on adhesion and clonal growth of h-iPS cells with maintained expression of
      pluripotency markers in a FGF-2 density-dependent manner. This is the first
      report of co-immobilization of an ECM derived molecule and a growth factor for
      stem cell culture.

PMID- 30274049
TI  - Collagen-silica nanocomposites as dermal dressings preventing infection in vivo.
AB  - The controlled delivery of multiple drugs from biomaterials is a timely
      challenge. In particular the nanocomposite approach offers a unique opportunity
      to combine the scaffold-forming ability and biocompatibility of hydrogels with
      the versatile and tunable drug release properties of micro- or nano-carriers.
      Here, we show that collagen-silica nanocomposites allowing for the prolonged
      release of two topical antibiotics are promising medicated dressings to prevent
      infection in wounds. For this purpose, core-shell silica particles loaded with
      gentamicin sulfate and sodium rifamycin were combined with concentrated collagen
      type I hydrogels. A dense fibrillar network of collagen exhibiting its typical
      periodic banding pattern and a homogenous particle distribution were observed by
      scanning electron microscopy. Antibiotics release from nanocomposites allowed a
      sustained antibacterial effect against Staphylococcus aureus over 10 days in
      vitro. The acute dermal irritation test performed on albino rabbit skin showed no
      sign of severe inflammation. The antibacterial efficiency of nanocomposites was
      evaluated in vivo in a model of cutaneous infection, showing a 2 log steps
      decrease in bacterial population when loaded systems were used. In parallel, the
      histological examination indicated the absence of M1 inflammatory macrophages in
      the wound bed after treatment. Taken together, these results illustrate the
      potentialities of the nanocomposite approach to develop collagen-based
      biomaterials with controlled dual drug delivery to prevent infection and promote
      cutaneous wound repair.

PMID- 30274050
TI  - Chitosan/alginate nanoparticles as a promising approach for oral delivery of
      curcumin diglutaric acid for cancer treatment.
AB  - Curcumin diglutaric acid (CG) is a prodrug of curcumin that shows better
      solubility and antinociceptive activity compared to curcumin. To improve its
      properties further, CG was encapsulated into polysaccharide-based nanoparticles
      in this study. A chitosan/alginate nanoparticulate system was chosen for
      encapsulation of CG due to its biocompatibility, biodegradability, non-toxicity,
      mucoadhisiveness and good film formation. CG-loaded chitosan/alginate
      nanoparticles were prepared by o/w emulsification and ionotropic gelification,
      with the conditions optimized using response surface methodology. A
      chitosan/alginate mass ratio of 0.04:1, CG concentration of 3 mg/mL and
      Pluronic(r)F127 concentration of 0.50% (w/v) were determined to be optimal for
      the nanoparticle preparation. FTIR and XRD confirmed encapsulation of CG into the
      chitosan/alginate nanoparticles. The CG-loaded chitosan/alginate nanoparticles
      showed better stability under UV radiation and in a simulated gastrointestinal
      environment, compared to a CG dispersion in water. The nanoparticles showed slow
      cumulative release of CG in simulated gastrointestinal fluids without enzymes and
      in body fluid. A Weibull model of the best fit for all conditions suggested that
      the release pattern of CG from CG-loaded chitosan/alginate nanoparticles was
      mainly controlled by Fickian diffusion and erosion of polymer materials. Finally,
      CG-loaded chitosan/alginate nanoparticles showed higher in vitro cellular uptake
      in human epithelial colorectal adenocarcinoma (Caco-2 cells) and better
      anticancer activity against Caco-2, human hepatocellular carcinoma (HepG2) and
      human breast cancer (MDA-MB-231) cells. Therefore, the CG-loaded
      chitosan/alginate nanoparticles are a promising approach for oral administration
      of CG for cancer treatment.

PMID- 30274051
TI  - Bioinspired gold nanoparticles decorated reduced graphene oxide nanocomposite
      using Syzygium cumini seed extract: Evaluation of its biological applications.
AB  - The development of novel functionalized reduced graphene oxide nanocomposite
      materials keeping in mind environmental and health perspectives via green
      approaches is currently gaining enormous research interest in the field of
      nanoscience and nanotechnology. Herein, we report a bio-inspired green synthesis
      approach for gold nanoparticles decorated reduced graphene oxide nanocomposite in
      which Syzygium cumini seed extract (SCSE) is applied as natural reducing and
      stabilizing agent for the simultaneous reduction of chloroauric acid and graphene
      oxide (GO). The obtained nanocomposite was thoroughly investigated using UV
      visible and FT-IR spectroscopy, XRD, SEM-EDX, TEM-SAED, Raman spectroscopy and
      XPS analysis. These characterization techniques clearly confirmed the successful
      synthesis of gold nanoparticles decorated reduced graphene oxide nanocomposite.
      In addition, this study evaluated the systematic and detailed analysis of AuNPs
      rGO-NC and its efficacy towards cellular and antibacterial toxicological
      behavior. A detailed in-vitro cytotoxicity study was performed by analysing the
      percentage inhibition of cell viability, generation of reactive oxygen species
      (ROS) in cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay on human colorectal (HCT116) and lung (A549) cancer cell
      lines. Further, antibacterial toxicological evaluation was performed by analysing
      diameter of inhibition Zone (DIZ), activity index (AI), minimum bactericidal
      concentration (MBC), minimum inhibitory concentration (MIC), growth kinetics
      (GrK) and death kinetics (DeK) against Gram-negative bacterial strain Escherichia
      coli and Gram-positive bacterial strains Staphylococcus aureus and Bacillus
      subtilis. The cytotoxicity and antibacterial toxicological assays revealed that
      the synthesized nanocomposite showed significant anti-cancer activity towards
      A549 cell line and Gram-negative bacterial strain Escherichia coli compared to
      the rest.

PMID- 30274052
TI  - Multifunctional graphene-based magnetic nanocarriers for combined hyperthermia
      and dual stimuli-responsive drug delivery.
AB  - The synthesis of hydrophilic graphene-based yolk-shell magnetic nanoparticles
      functionalized with copolymer pluronic F-127 (GYSMNP@PF127) is herein reported to
      achieve an efficient multifunctional biomedical system for mild hyperthermia and
      stimuli-responsive drug delivery. In vitro tests revealed the extraordinary
      ability of GYSMNP@PF127 to act as smart stimuli-responsive multifunctional
      nanomedicine platform for cancer therapy, exhibiting (i) an outstanding loading
      capacity of 91% (w/w, representing 910 MUg mg-1) of the chemotherapeutic drug
      doxorubicin, (ii) a high heating efficiency under an alternating (AC) magnetic
      field (intrinsic power loss ranging from 2.1-2.7 nHm2 kg-1), and (iii) a dual pH
      and thermal stimuli-responsive drug controlled release (46% at acidic tumour pH
      vs 7% at physiological pH) under AC magnetic field, in just 30 min. Additionally,
      GYSMNP@PF127 presents optimal hydrodynamic diameter (DH = 180 nm) with negative
      surface charge, high haemocompatibility for blood stream applications and tumour
      cellular uptake of drug nanocarriers. Due to its physicochemical, magnetic and
      biocompatibility properties, the developed graphene-based magnetic nanocarrier
      shows high promise as dual exogenous (AC field)/endogenous (pH) stimuli
      responsive actuators for targeted thermo-chemotherapy, combining magnetic
      hyperthermia and controlled drug release triggered by the abnormal tumour
      environment. The presented strategy and findings can represent a new way to
      design and develop highly stable added-value graphene-based nanostructures for
      the combined treatment of cancer.

PMID- 30274053
TI  - Individual and simultaneous electrochemical determination of metanil yellow and
      curcumin on carbon quantum dots based glassy carbon electrode.
AB  - Adulteration of medicinally valuable curcumin (CU) with harmful chemicals as
      metanil yellow (MY) in recent years have demanded for quick detection techniques
      of the adulterants. The voltammetric behavior of CU and MY on bare glassy carbon
      electrode (BGCE) and carbon quantum dots modified glassy carbon electrode
      (CQDs/GCE) was studied by both cyclic voltammetry (CV) and differential pulse
      voltammetry (DPV) in phosphate buffer solution of pH 5.4. The MY responded to the
      CQDs/GCE with two anodic peaks at -0.004 V and 0.136 V and two cathodic peaks at 
      0.112 and -0.048 V. Under similar conditions CU exhibited two anodic peaks at
      0.28 V and 0.55 V and one cathodic peak at 0.25 V. The overlapped voltammogram
      obtained for CU and MY on BGCE was well separated on the CQDs/GCE. The
      interference studies revealed that the compounds, demethoxycurcumin and
      bisdemethoxycurcumin, which are commonly associated with CU, did not interfere
      with the detection of MY. Real sample was analyzed with fabricated electrode and
      the recovery values >98% were obtained.

PMID- 30274054
TI  - Bioadhesive immobilize agarase on magnetic ferriferous by polydopamine.
AB  - The combined action of dopamine-iron coordination reaction and dopamine self
      polymerization was employed to immobilize agarase on the surface of Magnetic
      ferriferous oxide (MFO). The solid-liquid separation was easily realized in
      magnetic field due to the magnetic carrier. The immobilization process was taken
      by dopamine self-polymerization in room temperature, aqueous solution and neutral
      pH without organic solvent. Magnetic ferriferous oxide was prepared through
      coprecipitation. Then, MFO and dopamine were reacted under mild conditions to
      prepare the magnetic ferriferous oxide-polydopamine (MFO-PDA) complex. The MFO
      PDA complex was used in enzyme immobilization. It showed that the average enzyme
      activity yield was 63.9% in Immobilized enzyme, and the relative enzyme activity
      of the immobilized enzyme was still above 50% even after five times of reuse in
      addition, the MFO-PDA complex had good immobilization capacity toward agarase,
      and the immobilized enzyme has good reusability.

PMID- 30274055
TI  - Autofluorescence-aided assessment of integration and MU-structuring in
      chitosan/gelatin bilayer membranes with rapidly mineralized interface in
      relevance to guided tissue regeneration.
AB  - Beyond providing barrier function, the advanced materials in guided tissue
      regeneration (GTR) concept are further prompt to foster regeneration of distinct
      interfacing tissues. Herein we develop chitosan (CHT)/gelatin (GEL) bilayer
      membranes via successive solvent- and freeze-casting procedures and genipin (GEN)
      cross-linking chemistry. By utilizing the autofluorescence signal from GEN cross
      linking products (i.e. the secondary CHT (GEL) amines and GEN esters), the
      Confocal Fluorescent Microscopy (CFM) identifies the chemical inter-linking as
      well as physical integration between interface layers. The presence of non- and
      highly MU-porous and pore-interconnecting regions is demonstrated within cross
      sections of membranes with (by weight) prevalent GEL contribution in contrast to
      the sheet-like organization in membrane with equal presence of components. The
      constant processing conditions on variable compositions did not significantly
      affect the pore size distributions (in 1-230 MUm range), while pore wall
      thickness increase up to 220 MUm with GEL increase, which also improves the yield
      stress at compression (from 10 kPa to 19 kPa) and elastic modulus (from 26 kPa to
      34 kPa). The rapid mineralization procedure resulted in deposition of non-regular
      to spherical minerals, containing nonstoichiometric carbonated apatite with Ca/P
      ration in 1.7-2 range, which demonstrates formation of osseointegrative
      interface. The fast and high (up to 580%), composition-dependent swelling, as
      well as 67% to 100% weight loss in 4 weeks in vitro degradation experiment point
      on membranes' relevance in GTR.

PMID- 30274056
TI  - Evaluation of antibacterial and cytotoxic properties of green synthesized
      Cu2O/Graphene nanosheets.
AB  - Graphene nanocomposites have received attention for the therapy and detection of
      diseases. In this study, we developed a simple and green chemistry approach for
      synthesizing Cu2O/graphene nanocomposites (Cu2O/G) using date palm fruit syrup as
      a reducing agent. The graphene oxide surface anchored with Cu(OH)2 and reduced it
      to fabricate Cu2O-anchored graphene nanosheets using date palm fruit syrup.
      Physicochemical characteristics of the synthesized nanocomposites were analyzed.
      Scanning electron microscopy images revealed 50-70 nm Cu2O nanostructures
      anchored on the surface of crumpled graphene sheets. The Cu2O/G nanocomposites
      inhibited the gram-negative and gram-positive bacterial growth at 300 MUg. When
      compared with Cu2O nanoparticles and graphene oxide nanosheets (GO), Cu2O/G
      nanocomposite exhibited outstanding bactericidal activity. The cytotoxic
      properties of the prepared nanocomposites were studied in human mesenchymal stem
      cells (hMSCs). The Cu2O/G nanocomposites did not reduced cell viability by up to
      200 MUg/mL and slightly induced cell death at high concentrations. However, Cu2O
      nanoparticles and GO have significantly reduced the cell viability in hMSCs. The
      microscopic images of cellular and nuclear morphology suggested that the Cu2O/G
      composites did not cause major changes to hMSCs. The Cu2O nanoparticles and GO
      remarkably triggers the cellular damages, nuclear condensation and DNA
      fragmentation in hMSCs. Our study results revealed that Cu2O/G has excellent
      antibacterial activity with good biocompatibility. Thus, Cu2O/G could be used as
      a promising antibacterial agent in various purposes.

PMID- 30274057
TI  - Synthesis, characterization & cytocompatibility of poly (diol-co-tricarballylate)
      based thermally crosslinked elastomers for drug delivery & tissue engineering
      applications.
AB  - The aim of this study was to investigate the synthesis and in vitro
      characterization of thermoset biodegradable poly (diol-co-tricarballylate) (PDT)
      elastomeric polymers for the purpose of their use in implantable drug delivery
      and tissue engineering applications. The synthesis was based on thermal
      crosslinking technique via a polycondensation reaction of tricarballylic acid
      with aliphatic diols of varying chain lengths (C6-C12). PDT prepolymers were
      synthesized at 140  degrees C for 20 min. After purification, the prepolymers
      were molded and kept at 120  degrees C for 18 h under vacuum to complete the
      crosslinking process. PDT prepolymers were characterized by DSC, FT-IR, 1H NMR
      and GPC. The PDT elastomers were also subjected to thermal and structural
      analysis, as well as sol content, mechanical testing, in vitro degradation and
      cytocompatibility studies. The mechanical properties and sol content were found
      to be dependent on synthesis conditions and can be controlled by manipulating the
      crosslinking density and number of methylene groups in the chain of precursor
      aliphatic diol. The family of thermally crosslinked PDT biodegradable polyesters
      were successfully prepared and characterized; besides they have promising use in
      drug delivery and other biomedical tissue engineering applications.

PMID- 30274058
TI  - Manipulation of osteoclastogenesis: Bioactive multiphasic silica/collagen
      composites and their effects of surface and degradation products.
AB  - The intent of the present study was to demonstrate that multiphasic
      silica/collagen xerogels are able to manipulate cellular processes. These
      xerogels were prepared by a sol-gel approach allowing the incorporation of
      mineral phases. The resulting nanocomposites are designed as biomaterial for bone
      regeneration. Human osteoclasts derived from peripheral blood mononuclear cells
      were cultured both indirectly and directly, either in presence of different
      xerogel types or on their surface, to investigate the factor with the main
      influence on osteoclastogenesis. To this end, the incorporation of a third phase
      to silica/collagen xerogels was used to affect osteoclastogenesis. In cell
      culture, ambient ion conditions controlled by both the degradation products of
      the xerogel and the bioactivity-dependent ion release and reprecipitation were
      shown to have the main effect on osteoclast specific enzyme tartrate-resistant
      acid phosphatase (TRAP) 5b. Late stage of osteoclastogenesis characterized by
      resorption was strongly dependent on the xerogels composition. Surface chemistry
      of the xerogels was displayed to play an important role in osteoclast resorption.
      Biphasic silica/collagen xerogels and triphasic xerogels with calcium carbonate
      offered widespread resorbed areas, whereas hydroxyapatite containing xerogels
      showed distinctly reduced resorption. The incorporation of strontium carbonate
      and phosphate, respectively, as third phase changed TRAP 5b activity dose
      dependently and inhibited resorption within 21 days. Quantitative evaluation on
      osteoclast differentiation was carried out using biochemical methods (TRAP 5b,
      cathepsin K) and was supported by confocal laser scanning microscopy and scanning
      electron microscopy (SEM). Qualitative estimation of resorption was carried out
      by SEM.

PMID- 30274059
TI  - Insights on the intracellular trafficking of PDMAEMA gene therapy vectors.
AB  - It is known that an efficient gene therapy vector must overcome several steps to
      be able to express the gene of interest: (I) enter the cell by crossing the cell
      membrane; (II) escape the endo-lysosomal degradation pathway; (III) release the
      genetic material; (IV) traffic through the cytoplasm and enter the nucleus; and
      last (V), enable gene expression to synthetize the protein of interest. In recent
      years, we and others have demonstrated the potential of poly(2-(N,N'
      dimethylamino)ethylmethacrylate) (PDMAEMA) as a gene therapy vehicle. Further
      optimization of gene transfer efficiency requires the understanding of the
      intracellular pathway of PDMAEMA. Therefore the goal of this study was to
      determine the cellular entry and intracellular trafficking mechanisms of our
      PDMAEMA vectors and determine the gene transfer bottleneck. For this, we have
      produced rhodamine-labeled PDMAEMA polyplexes that were used to transfect retinal
      cells and the cellular localization determined by co-localization with cellular
      markers. Our vectors quickly and efficiently cross the cell membrane, and escape
      the endo-lysosomal system by 24 h. We have observed the PDMAEMA vectors to
      concentrate around the nucleus, and the DNA load to be released in the first 24 h
      after transfection. These results allow us to conclude that although the endo
      lysosomal system is an important obstacle, PDMAEMA gene vectors can overcome it.
      The nuclear membrane, however, constitutes the bottleneck to PDMAEMA gene
      transfer ability.

PMID- 30274060
TI  - Praziquantel systems with improved dissolution rate obtained by high pressure
      homogenization.
AB  - Praziquantel (PZQ), an antihelmintic agent commonly administered to humans and
      cattle, has low aqueous solubility, which compromises its bioavailability and
      efficacy. The purpose of this study was to develop a new formulation, in order to
      improve PZQ dissolution rate. PZQ dispersions have been developed by high
      pressure homogenization (HPH) using different stabilizers, selected upon PZQ
      saturation solubility. After the screening, two promising formulations were
      developed, combining poloxamer 188 with polyvinylpyrrolidone or maltodextrin.
      Characterization studies including particle size distribution, crystallinity,
      morphology, drug content, and in vitro dissolution profiles, were performed over
      selected formulations. The scanning electronic micrographs revealed that the
      morphology of suspended particles corresponded to elongated shapes, with an
      average particle size close to the micron range. X-ray powder diffractometry and
      differential scanning calorimetry results confirmed the drug crystallinity,
      before and after the HPH process. Besides, differential scanning calorimetry
      revealed the absence of interactions between PZQ and excipients. The dissolution
      rate of PZQ dispersions was significantly enhanced compared with raw PZQ, either
      in phosphate buffer or hydrochloric acid, mainly due to particle size reduction,
      thus improved saturation solubility.

PMID- 30274061
TI  - Incorporation of zinc oxide nanoparticles improved the mechanical, water vapor
      barrier, UV-light barrier, and antibacterial properties of PLA-based
      nanocomposite films.
AB  - Zinc oxide nanoparticles (ZnO NPs) were synthesized using zinc chloride and NaOH
      and they were incorporated to prepare PLA/ZnO NPs composite films. The SEM images
      showed that the ZnO NPs were cubical in shape with size ranged from 50 to 100 nm,
      and the PLA/ZnO NPs composite films were smooth and compact. The composite films
      exhibited strong UV-light barrier property with a slight decrease in the
      transparency. The thickness, tensile strength, and water vapor barrier property
      of the films increased significantly after incorporation of ZnO NPs. The TS of
      PLA films increased by 37.5%, but the WVP decreased by 30.5% from 3.11 * 10-11 to
      2.16 * 10-11 g m/m2.Pa.s when 0.5 wt% of ZnO NPs was incorporated. The composite
      films exhibited potent antibacterial activity against food-borne pathogenic
      bacteria, Escherichia coli and Listeria monocytogenes. The developed films were
      applied to the packaging of a minced fish paste and showed strong antibacterial
      function. The prepared composite films could be used as antibacterial and UV
      light barrier films for food packaging and biomedical applications.

PMID- 30274062
TI  - A method for visualization and isolation of elastic fibres in annulus fibrosus of
      the disc.
AB  - A simple and cost effective protocol for visualization and isolation of the
      elastic fibres network in the annulus fibrosus (AF) of the disc is explained, to
      provide other researchers a method that can be applied in disc ultra-structural
      analysis, biomechanical assessment of elastic fibre and tissue engineered
      scaffold fabrication. This protocol is developed based on simultaneous sonication
      and alkali digestion of tissue that eliminates all matrix constituents except for
      elastic fibres, which is applicable for different species including human. Thin
      samples harvested from ovine, bovine, porcine and human, which are commonly used
      in disc research, were exposed to 0.5 M sodium hydroxide solution along with
      sonication (25 kHz) in distilled water for defined periods of time at room
      temperature. Post heat treatment removed collagen fibres via the gelatinization
      process, for visualization of elastic fibres.

PMID- 30274063
TI  - The physical features -size and granularity- of solid materials are strongly
      affected by trituration in lactose, before turning them into homeopathic
      solutions.
AB  - Trituration is a mechanical process (a form of comminution) for reducing the
      particle size of a substance. In this manuscript, six different Raw Solid
      Materials (RSM) which are used in Homeopathy after successive grindings are
      studied before they are turned into homeopathic solutions. The impact of
      trituration, with the presence of alpha-lactose monohydrate (milk sugar) seems to
      be quite great and interesting because of the variety of grain size which largely
      differentiate the properties of the materials. The grain sizes obtained
      triturations by hand according to C. Herring's suggestion leads, finally,
      measurement scale dimensions. The obtained results can be useful information for
      all the pharmacy industries, as well as for preparing any kind of powder.

PMID- 30274064
TI  - Fabrication, antibacterial activity and cytocompatibility of quaternary ammonium
      chitooligosaccharide functionalized polyurethane membrane via polydopamine
      adhesive layer.
AB  - In this study, to enhance the antibacterial activity and cytocompatibility of the
      electrospinning polyurethane (PU) fibrous membrane, quaternary ammonium
      chitooligosaccharide (G-COS) was immobilized on the fibrous membrane surface via
      an intermediate layer of polydopamine (PDOPA) to obtain the G-COS functionalized
      PU (G-C-D-PU), as a control, chitooligosaccharide (COS) functionalized PU fibrous
      membrane (C-D-PU) was prepared, too. Surface composition, morphology,
      hydrophilicity and surface energy of the original and modified PU fibrous
      membranes were characterized, which revealed that the surface roughness and
      hydrophilicity of the PU fibrous membrane were obviously increased by modified
      with COS and G-COS, respectively. Antibacterial experiment against E. coli and S.
      aureus indicated that antibacterial activity of the G-C-D-PU fibrous membrane was
      markedly superior to that of pure PU and C-D-PU fibrous membranes. In vitro cells
      culture experiments revealed that the adhesion and proliferation of NIH-3T3 cells
      on the PU fibrous membrane were improved by successively immobilized with PDOPA
      and COS as well as G-COS with the concentration of 2 g/L and 6 g/L. Moreover, the
      G-C-D-PU fibrous membranes with relative high G-COS content were more beneficial
      to the enhancement of antibacterial activity, but on the contrary, those with
      relative low G-COS content were more in favor of cell attachment and
      proliferation.

PMID- 30274065
TI  - Enhanced biocompatibility of PAMAM dendrimers benefiting from tuning their
      surface charges.
AB  - The surface charge of dendrimers is one of the key factors that determine their
      use in nanomedicine. Generation 5 poly(amido amine) dendrimers (G5 PAMAM)
      encapsulating with fluorescein sodium were employed to study the method to tune
      surface charge. Firstly, the surface primary amines were reacted with maleic
      anhydride to introduce double bonds. Then, l-cysteine and cysteamine were
      conjugated to these double bonds via thiol-ene additions in water, respectively.
      The surface charges of modified G5 PAMAMs were successfully controlled by tuning
      the molar ratio of L-cysteine to cysteamine. The surface charges of the resulting
      modified G5 PAMAMs varied from -16.0 mV to -3.7 mV at physiological pH. In
      addition, they showed good compatibility with proteins and cells compared with G5
      PAMAM. Modified G5 PAMAMs and fibrinogen could coexist in solution without
      generating noticeable aggregation, while G5 PAMAM induces significant
      aggregation, indicating these modifications can effectively reduce the
      interaction force between G5 PAMAM and proteins. Furthermore, modified G5 PAMAMs
      exhibited negligible hemolysis, while G5 PAMAM caused severe hemolysis. The
      cytotoxicity assay demonstrated that modified G5 PAMAMs exhibited very low
      cytotoxicity to both HUVEC cells and KB cells (>90% cell viability) at high
      concentrations up to 2 mg/mL. The cellular uptake of them was much less efficient
      compared with that of G5 PAMAM. Moreover, the intravenous injected modified G5
      PAMAMs were excreted by kidney with a relatively little accumulation in liver,
      confirming their good biocompatibility in vivo. It is expected that the modified
      G5 PAMAMs could be an excellent candidate for contrast agent carriers in the
      future.

PMID- 30274066
TI  - Studies on effect of CuO addition on mechanical properties and in vitro
      cytocompatibility in 1393 bioactive glass scaffold.
AB  - Copper doped bioactive glasses have been reported as the potential biomaterial
      for diseased or damaged bone repair and act as stimulants to new bones formation.
      In the present manuscript, we have synthesized 1393 derived glass based scaffold
      with the general formula of (54.6 - X)SiO2.6Na2O.7.9 K2O.7.7 MgO.22 CaO.1.74
      P2O5.XCuO (all are in mole%; where X = 0,1,2,3) through traditional melt-quench
      route and the samples were designated as 1393, 1393-1Cu, 1393-2Cu and 1393-3Cu
      respectively. Polymer foam with interconnected pores has been used on later stage
      to prepare porous (porosity > 50%) bioactive scaffolds. The addition of CuO in
      glass scaffolds was to ensure its cytocompatibility, ability to enhance cell
      proliferation and improvements in mechanical properties. Increasing trend of CuO
      in the 1393 glass scaffold has resulted in increasing compressive and flexural
      strength and elastic modulus of the scaffolds. In-vitro cellular growth
      inhibition and cell viability assay of CuO incorporated 1393 glass scaffolds
      demonstrated that it did not inhibit proliferation and viability of human
      squamous carcinoma cell (SCC-25) at low materials concentration. The materials
      caused moderate level of apoptosis at higher concentrations and were also
      tolerated by human RBC as studied by hemolytic assay. The results indicated that
      CuO incorporated 1393 scaffolds could be a potential biomaterial for neobone
      tissue engineering application.

PMID- 30274067
TI  - Fabrication and characterization of PCL/zein/gum arabic electrospun nanocomposite
      scaffold for skin tissue engineering.
AB  - The main role of tissue engineering is to produce the artificial tissue for
      replacing the biological functions in tissue regeneration and wounds healing. The
      purpose of this research was to produce porous nanofiber scaffold by
      electrospinning to compensate deep skin damages. In order to simulate a scaffold
      similar to the natural extracellular matrix of the skin, a mixture of corn
      protein (Zein), polycaprolactone (PCL) and gum arabic (GA) was used with
      different concentrations and ratios. Zein and GA polymers were used as a protein
      and polysaccharide component of the scaffold and PCL polymer for elasticity,
      strength and time setting of scaffold degradability. For investigating morphology
      and scaffold compounds, scanning electron microscopy (SEM) and Fourier transform
      infrared techniques were used. Furthermore, mechanical properties, porosity,
      water absorption and degradability in phosphate buffered saline (PBS) were
      investigated. Antibacterial properties, cell adhesion and proliferation were also
      evaluated. SEM results showed that fabricated PCL/Zein/GA scaffolds had a porous
      structure with bimodal diameters distribution. PCL/Zein/GA scaffolds showed high
      hydrophilic properties, favorable porosity (about 80%) and tensile strength of
      1.36-3 MPa with an elongation of 19.13-44.06% desirable for skin tissue
      engineering. SEM images of degraded specimens show that the scaffold retains its
      fibrous structure during its destruction. The results of bacterial culture
      indicated that the scaffold containing GA had antibacterial properties. Moreover,
      in vitro assays revealed favorable L929 cells proliferation compared to tissue
      culture polystyrene (control). Hence, the PCL/Zein/GA scaffold shows a good
      potential for application in skin tissue engineering.

PMID- 30274068
TI  - Inner layer-embedded contact lenses for ion-triggered controlled drug delivery.
AB  - Drug leakage during manufacturing and storage process is the main obstacle
      hindering the application of contact lenses as the carrier for extended ocular
      drug delivery. In this study, we have designed a novel inner layer-embedded
      contact lens capable of ion-triggered drug release for extended ocular drug
      delivery. Using betaxolol hydrochloride as a drug model, drug-ion exchange resin
      complex dispersed polymer film was used as an inner layer, and silicone hydrogel
      was used as an outer layer to fabricate inner layer-embedded contact lens.
      Influence of composition of the inner film and crosslinking degree of the outer
      hydrogel on drug release profile was studied and optimized for weekly use. The
      ion-triggered drug eluting property enables the inner layer-embedded contact lens
      being stable when stored in distilled water at 5  degrees C for at least 30 days
      with ignorable drug loss and negligible changes in drug release kinetics. In vivo
      pharmacokinetic study in rabbits showed sustained drug release for over 168 h in
      tear fluid, indicating significant improvement in drug corneal residence time. A
      level A IVIVC was established between in vitro drug release and in vivo drug
      concentration in tear fluid. In conclusion, this inner layer embedded contact
      lens design could be used as a platform for extended ocular drug delivery with
      translational potential for both anterior and posterior ocular disease therapy.

PMID- 30274069
TI  - Development of biodegradable electrospun gelatin/aloe-vera/poly(epsilon
      caprolactone) hybrid nanofibrous scaffold for application as skin substitutes.
AB  - Nowadays, aloe-vera (AV) is exploited extensively in nanofibrous structures for
      skin substitutes. However, the lack of electrospinnability and appropriate
      mechanical characteristics are the key limitations for this natural extract to be
      used in the form of nanofibrous mats. In this study, two commercially available
      biopolymers, gelatin (Gel) and poly(epsilon-caprolactone) (PCL), were chosen to
      improve these issues and double-nozzle electrospinning technique was used to
      fabricate hybrid scaffold from Gel/AV blend and PCL solutions. Response surface
      methodology was utilized to investigate the effect of electrospinning parameters
      (Gelatin concentration, Aloe-vera concentration and Gel/AV feed-rate) on the
      mechanical properties, morphology and hydrophilicity of nanofibers and the
      optimized scaffold was chosen for further studies. In order to verify the
      application of this scaffold in bioapplications, the chemical, thermal and
      biological features of scaffold were analyzed using FTIR, DSC, biodegradability,
      bactericidal, biocompatibility and drug-delivery. The results revealed that the
      presence of aloe-vera improved the antibacterial activity (>99% and 85.63%
      against Gram-positive and Gram-negative bacteria, respectively), and led to
      adequate in-vitro biodegradation. Furthermore, it was found that incorporation of
      aloe-vera increased the cell viability without any toxicity.

PMID- 30274070
TI  - Long-term real-time tracking live stem cells/cancer cells in vitro/in vivo
      through highly biocompatible photoluminescent poly(citrate-siloxane)
      nanoparticles.
AB  - Long-term live cell tracking is desirable and necessary to understand the
      dynamics and complexity of biological interactions in stem cells and cancer
      cells. Conventional live cells fluorescence trackers are generally non-degradable
      and are showing increased toxicity concerns during the long-term application.
      Previously we developed biodegradable fluorescent poly(citrate)-based hybrid
      elastomers for bone regeneration applications. Here, we fabricated the
      photoluminescent poly(citrate-siloxane) nanoparticles (PCSNPs) through an
      oil/water emulsion method and demonstrated their long-term live stem cells/cancer
      cells imaging applications. PCSNPs showed a uniform size distribution (mean
      diameter 120 nm) and highly stable dispersability (above 30 days) in various
      physiological medium, as well as excellent fluorescent properties and
      photostability. PCSNPs possess excellent cellular biocompatibility, which could
      be efficiently internalized by cells and selectively image the cell lysosome with
      a high photostability. Compared with commercial Cell TrackerTM Green and Cell
      TrackerTM Red, the adipose-derived mesenchymal stem cells or human hepatoma cells
      were stably labeled by PCSNPs for over 14 days as they grew and developed (7
      passages). Additionally, PCSNPs efficiently tracked cells up to 7 days in vivo
      through a non-invasively way compared with 1 day of commercial tracker. This
      study demonstrates an important strategy to design biodegradable multifunctional
      delivery platforms for biomedical applications such as long-term bioimaging.

PMID- 30274071
TI  - Controlled release of monoclonal antibodies from poly-l-lysine-coated alginate
      spheres within a scaffolded implant mitigates autoimmune responses to
      transplanted islets and limits systemic antibody toxicity.
AB  - Immunomodulatory monoclonal antibodies (IM-mAbs) are a cornerstone of modern
      immunotherapy; however, when administered systemically (i.e., via injection),
      these agents can generate a variety of negative side effects. For many diseases,
      systemic delivery of IM-mAbs is the most effective mode of treatment, but in
      instances where the cellular target occupies a limited, well-defined space (e.g.,
      solid tumors or cellularized implants) local, controlled release of IM-mAbs might
      be desirable. Antibodies are highly sensitive to a variety of environmental
      conditions, which limit the kinds of polymers suitable for antibody retention and
      controlled release. The present study evaluates the release of antibodies from
      biocompatible, 2-mm diameter alginate spheres coated with poly-l-lysine and a
      thin outer layer of alginate (APA spheres). In vitro, rates of antibody release
      (including IM-mAbs) could be incrementally decreased and made linear by
      incrementally increasing the quantity of poly-l-lysine deposited on the alginate,
      with linear release lasting in one scenario for at least 46 days. To evaluate the
      bioactivity in vivo of IM-mAbs, APA spheres loaded with either anti-CD3epsilon or
      anti-CD95 mAb were incorporated into scaffolded islet implant (SI) test-beds and
      the SIs implanted into a mouse model of autoimmune (type 1) diabetes. Release of
      mAbs within the implanted SIs resulted in reduced autoimmune responses to both
      transplanted and native islets. Notably, mice implanted with APA spheres loaded
      with quantities of anti-CD95 mAb that would be lethal if given systemically
      showed immunomodulation with no toxic side effects. Collectively, our results
      indicate that APA spheres are a relatively simple means to evaluate the effects
      of local, controlled release of IM-mAbs in a way that preserves mAb function and
      limits systemic toxicity.

PMID- 30274072
TI  - Precise design and synthesis of an AIE fluorophore with near-infrared emission
      for cellular bioimaging.
AB  - Organic fluorophores emerge as important stains for bioimaging and biosensing,
      especially for fluorophores with aggregation-induced emission characters.
      However, the development of organic fluorophores with efficient AIE properties
      expand to far-red and/or near-infrared is still a great challenge. Herein, we
      precisely design and synthesize a novel D-pi-A type of near-infrared AIE
      fluorophore (TPE-PTZ-R) by introducing phenothiazine (PTZ) to modify the typical
      AIE unit (tetraphenylethylene, TPE). TPE-PTZ-R displays good optical properties
      including a large Stokes shift and typical AIE properties. We next fabricate the
      uniform and stable AIE nanoparticles by loading Pluronic F127 and apply it in
      cellular bioimaging with high uptake efficiency, low cytotoxicity and good
      photostability.

PMID- 30274073
TI  - Mesoporous silicas templated by heterocyclic amino acid derivatives: Biomimetic
      synthesis and drug release application.
AB  - The present paper reported a biomimetic synthesis of mesoporous silicas (BMSs) at
      room temperature by using synthesized polymers (C16-l-His, C16-l-Pro and C16-l
      Trp) which derived from amino acid with ring structures as template under basic
      condition via co-structural-directing-agent method. The formation mechanism of
      BMSs and effect of initial synthesis conditions (such as surfactant structure, pH
      and co-solvents) on morphology and structure of BMSs were systematically studied.
      Synthesized BMSs were characterized by transmission electron microscope (TEM), X
      ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and
      nitrogen adsorption/desorption isotherms. The results showed that the surfactant
      structure was the dominant factor to direct the final mesostructure of BMSs,
      since the structure of surfactant affected the structure and size of clusters.
      Meanwhile the generation of BMSs required very rigorous alkaline condition which
      controlled the ionization degree of the surfactant and thus contributing to
      adequate stacking energy. Higher pH resulted in construction of channels with
      higher curvature. The presence of ethanol was found to facilitate the formation
      of BMSs with larger particle size. In application, aspirin can be loaded into
      BMSs with high efficiency, and the drug crystalline state of aspirin transformed
      from crystalline state to amorphous state during this process, which undoubtedly
      lead to the improvement of drug dissolution from 72.8% to 100% within 90 min. It
      is convincible that the biomimetic method presented here provided novel insight
      on precisely control of mesoporous silica and undoubtedly promoted the
      application of mesoporous silica materials.

PMID- 30274074
TI  - Electrospun mucosal wound dressings containing styptics for bleeding control.
AB  - Two major aspects need to be focused to accelerate wound healing of mucosal
      damages especially in the field of otorhinolaryngology. (i) The problem of
      application due to the small access during surgery, (ii) the fixation of the
      wound dressing to reveal a stable healing process. In the present work the high
      request to a mucosal wound dressing which additionally support hemostasis was
      addressed. We developed an electrospun fabric made of poly(l-lactide-co-d/l
      lactide) (PLA) which can be loaded with the hemostatic agents adrenaline and
      tranexamic acid to cover mucosal lesions analogues to common skin patches. These
      loaded electrospun fabrics were demonstrated to be biocompatible, thin and
      flexible, and thus could be adapted individually to the mucosal defect with
      respect to localization and size of the lesion. The treatment of mucosal defects
      with these loaded PLA wound dressings induced a faster and time controlled
      hemostatic reaction, which significantly improved the healing process.

PMID- 30274075
TI  - Synthesis of fluorescent silicon quantum dots for ultra-rapid and selective
      sensing of Cr(VI) ion and biomonitoring of cancer cells.
AB  - A facile one-step synthetic approach was developed for fabrication of fluorescent
      silicon quantum dots (Si QDs) and used as a probe for fluorescence detection of
      hexavalent chromium (Cr (VI)) in environmental water samples. The as-prepared Si
      QDs exhibit a strong fluorescence emission peak at 520 nm with a quantum yield of
      14.2%. The fluorescent Si QDs were rapidly produced by using ascorbic acid as a
      reductant at 55  degrees C. The emission peak of Si QDs at 420 nm was effectively
      quenched upon the addition of Cr(VI). The Si QDs acted as the best fluorescent
      probe for the detection of Cr(VI) at PBS pH 7.4. The developed probe possessed a
      good linear correlation (R2 = 0.992) between Cr(VI) concentration (1.25-40 MUM)
      and the (F0-F)/F0 values with a detection limit of 0.65 MUM. Furthermore, the Si
      QDs served as a bio-probe for fluorescence imaging of A549 lung cancer cells and
      cell viability results confirmed the good biocompatible nature of Si QDs. The as
      fabricated Si QDs show several advantages such as rapidity, selectivity and
      biocompatibility for sensing of Cr(VI) and imaging of A549 cells, which opens a
      facile analytical platform for environmental and bioimaging applications.

PMID- 30274076
TI  - Molecular analysis of biocompatibility of anodized titanium with deposited silver
      nanodendrites.
AB  - Titanium (>99.6% purity) and its anodically oxidized modifications, with and
      without deposited silver nanodendrites regarding its biocompatibility were
      evaluated. In human gingival fibroblasts and osteoblast cell lines grown on
      tested samples, the level of expression of genes encoding alphaV (ITGAV) and
      beta1 (ITGB1) integrin subunits also genes encoding focal adhesion (FAK) and
      extracellular-signal regulated (ERK) kinases was assessed. For this purpose, the
      qualitative and quantitative PCR technique was used. The expression of studied
      genes was dependent on the origin of cell lines and the type of evaluated
      material. The high expression of PBGD and ITGAV genes in fibroblasts grown on the
      surface of anodically modified titanium with deposited silver nanodendrites
      indicates potentially high biocompatibility of these samples for soft tissue
      cells. The high expression of the ITGB1 and ERK1 genes and the enhanced
      expression of the FAK gene in osteoblasts cells grown on the tested material was
      also observed. Summarizing, the nanocrystalline Ti modified with silver deposits
      showed higher biocompatibility in comparison with the conventional pure Ti
      samples.

PMID- 30274077
TI  - Self-assembling peptide and nHA/CTS composite scaffolds promote bone regeneration
      through increasing seed cell adhesion.
AB  - Porous scaffolds fabricated with nano-hydroxyapatite (nHA) and chitosan (CTS),
      are widely used in bone tissue engineering (BTE). However, cell adhesion is
      relatively poor in nHA/CTS scaffolds, which also do not provide an ideal three
      dimensional environment for seed cells. These deficiencies limit the
      applicability of these BTE scaffolds to repair bone defects. To address these
      challenges, we designed a composite scaffold that combines nHA/CTS with self
      assembling peptide (SAP), a material which is similar to the extracellular
      matrix. We found that SAP/nHA/CTS scaffolds both increased the adhesion of bone
      mesenchymal stem cells (BMSCs) and enhanced the mechanical properties of the
      scaffold. This composite scaffold was then used to repair a femoral condylar bone
      defect in a mouse model. Healing and mineralization was demonstrated after 12
      weeks using H&E staining, microcomputerized tomography, and bone mineral density
      tests. To our knowledge, this is the first report that SAP/nHA/CTS scaffolds can
      increase cell adhesion and promote the reconstruction of femoral condylar bone
      defects. Moreover, this study indicates that BTE using a SAP/nHA/CTS scaffold may
      be a novel prospective strategy for healing extensive bone defects.

PMID- 30274078
TI  - Accelerated wound healing and its promoting effects of biomimetic collagen
      matrices with siderophore loaded gelatin microspheres in tissue engineering.
AB  - The prolonged inflammation and elevation of Matrix Metalloproteniases (MMPs) at
      the wound site causes significant degradation of Extracellular matrix (ECM) which
      cause delays the process of wound healing. Hence the development of therapeutic
      dressing matrices to control and to positively regulate MMPs balance was
      considered important in achieving faster healing. The design of biomaterial
      matrices of collagen scaffold has the challenge to mimic the function of ECM and
      emulate to the attraction of fibroblast migration at wound site. Herein, we
      report the fabricated Collagen (COL) matrices impregnated with Siderophore loaded
      Gelatin Microspheres (SGM) as a delivery system to control both infection and
      protease levels in the wound site for accelerated healing. The fabricated
      collagen scaffold impregnated with siderophore loaded gelatin microspheres (COL
      SGM) was characterized physiochemically using Fourier transform infrared
      spectroscopy (FTIR), Scanning electron microscopy (SEM) and swelling behaviour.
      The COL-SGM scaffold possesses good swelling ability and also exhibited better
      morphology for the cell adhesion and proliferation. The in vitro biocompatibility
      and in vitro fluorescence activity of the developed scaffold revealed to possess
      good cell proliferation and migration against NIH 3T3 fibroblast and Human
      keratinocytes (HaCaT) cell lines. Furthermore, the in vivo evaluation offered the
      advantage of neutralizing the excessive proteases and delivered the siderophore
      in controlled fashion depending on the level of wound exudates with modulated
      MMPs. Moreover, the COL-SGM scaffold exhibited with increase in the collagen
      synthesis and faster reepitheliazation of wounds. Thus the developed COL-SGM
      scaffold achieved improvements in biocompatibility and act as a potent MMP
      inhibitor to improve wound healing efficiency in tissue engineering application.

PMID- 30274079
TI  - Effect of silver nanoparticles in the induction of apoptosis on human
      hepatocellular carcinoma (HepG2) cell line.
AB  - Silver nanoparticles (Ag NPs) serve numerous chief functions in cosmetics,
      engineering, textile, food technology and medicine. These nanoparticles are also
      utilized in the pharmaceutical industry particularly in the production of novel
      antimicrobial agents. However, despite the various studies of Ag NPs induced
      toxicity, there is a lack of information concerning cellular toxicity mechanisms
      of these nanoparticles on human cells. In the current project, we investigate the
      anti-cancer effects of Ag NPs in HepG2 (liver hepatocellular adenocarcinoma)
      cells. The mean particle size and morphology for the prepared nanoparticles were
      determined by dynamic light scattering (DLS) and transmission electron microscopy
      (TEM), respectively. Cell viability, reactive oxygen species (ROS) formation,
      cytochrome c amount and expression level of BAX/CASP 3/CASP 8/CASP 9 were assayed
      in HepG2 cells after incubation with Ag NPs. The prepared nanoparticles showed
      the mean particle size of 30.71 nm with polydispersity index (PDI) of 0.21. Our
      results revealed decreased cell viability in a concentration-dependent manner and
      the IC50 of 75 MUg/mL for Ag NPs. Ag NPs cytotoxicity was associated with
      induction of ROS and cell apoptosis in HepG2 cell line. According to our
      findings, Ag NPs could be considered as potential chemotherapeutic agents in the
      treatment of liver hepatocellular carcinoma.

PMID- 30274080
TI  - Protective nature of low molecular weight chitosan in a chitosan-Amphotericin B
      nanocomplex - A physicochemical study.
AB  - Chitosan, a biopolymer of immense potential, has been well-explored over the past
      decade in the biomedical field. Despite its numerous biological properties like
      anti-microbial, anti-inflammatory, anti-diabetic etc., limited studies have been
      conducted on its ability to protect therapeutic molecules in nano-formulations.
      Amphotericin B (AMP) is one such therapeutic molecule which requires protection
      as it possesses inherent limitations of poor water-solubility, susceptibility to
      oxidation- and/or light-induced degradation etc. Although AMP formulations have
      been quite successful in treating chronic fungal infections, their high cost,
      prolonged nature of therapy and instability over longer durations has
      necessitated the development of alternative carriers. In the present study, a
      stable nanoparticulate formulation was successfully prepared using low molecular
      weight chitosan and the anti-fungal agent AMP and this was found to offer
      protection to the labile AMP. The developed nanocomplexes could prevent
      degradation of AMP up to six months, in solution form, unlike the native drug
      which degraded in <24 h. Antifungal studies of the developed nanocomplexes
      revealed a surface charge-dependent antifungal activity. Furthermore, the
      nanocomplexes did not affect the viability of mammalian cells and showed
      excellent intracellular uptake and retention, and hence suggested potential of
      the nanocomplexes in alleviating systemic fungal infections.

PMID- 30274081
TI  - Study of chemical, physico-mechanical and biological properties of 4,4'
      methylenebis(cyclohexyl isocyanate)-based polyurethane films.
AB  - : Polyurethane films were obtained in the solvent-free cycloaliphatic
      polyaddition process of 4,4'-methylenebis(cyclohexyl isocyanate), poly(epsilon
      caprolactone) diol or poly(oxytetramethylene) glycol and 1,4-butanediol. Chemical
      structures of the polymers were confirmed by FTIR, NMR and GPC methods. Their
      surface, thermal and mechanical properties have been evaluated. Results of
      biological studies with polyurethane films as potential biomaterials for medical
      applications revealed their mild cytotoxicity against normal human fibroblasts
      (BJ) and immortalized keratinocytes (HaCaT). STATEMENT OF SIGNIFICANCE: The
      research is relevant for the potential uses of polyurethane films made from
      commercial raw materials as general medical supplies.

PMID- 30274082
TI  - Copper-polyaniline nanocomposite: Role of physicochemical properties on the
      antimicrobial activity and genotoxicity evaluation.
AB  - Copper nanoparticles (Cu NPs) have proven to own excellent antimicrobial
      efficacy, but the problems of easy oxidation and aggregation limit their
      practical application. Here, nanocomposite based on polyaniline (PANI) and Cu NPs
      solved this problem and brought additional physicochemical properties that are
      markedly advantageous for antimicrobial applications. Current work exploits this
      potential, to examine its time- and concentration-dependent antimicrobial
      activity, employing E. coli, S. aureus, and C. albicans as a model microbial
      species. Regarding the presence of polaronic charge carriers in the fibrous
      polyaniline network, effects of Cu NPs' size and their partially oxidized
      surfaces (the data were confirmed by HRTEM, FESEM, XRD, Raman and XPS analysis),
      as well as rapid copper ions release, Cu-PANI nanocomposite showed efficient
      bactericidal and fungicidal activities at the concentrations <=1 ppm, within the
      incubation time of 2 h. Beside the quantitative analysis, the high levels of
      cellular disruption for all tested microbes were evidenced by atomic force
      microscopy. Moreover, the minimum inhibitory and bactericidal concentrations of
      the Cu-PANI nanocomposite were lower than those reported for other
      nanocomposites. Using such low concentrations is recognized as a good way to
      avoid its toxicity toward the environment. For this purpose, Cu-PANI
      nanocomposite is tested for its genotoxicity and influence on the oxidative
      status of the human cells in vitro.

PMID- 30274083
TI  - Effect of annealing temperature on mechanical and antibacterial properties of Cu
      bearing titanium alloy and its preliminary study of antibacterial mechanism.
AB  - Cu-bearing titanium alloys are designed and studied as a novel medical metal
      material with antibacterial function. However, the addition of Cu would affect
      the mechanical properties of titanium alloy more or less, especially the
      ductility, despite its excellent antibacterial property. Thus, the aim of this
      study was to optimize the heat treatment for Cu-bearing titanium alloys in order
      to achieve a balance of satisfactory mechanical, antibacterial and other
      properties. In this study, Ti6Al4V-5 wt% Cu alloy was fabricated, and then
      different annealing treatments with various heating temperatures (700-910 
      degrees C) were employed on the alloy. The effects of heating temperature on
      microstructure evolution, mechanical properties, corrosion resistance and
      antibacterial performance of Ti6Al4V-5Cu alloy were systematically studied. It
      was found that annealing at 740  degrees C for Ti6Al4V-5Cu alloy showed the best
      comprehensive properties of high strength, excellent ductility, corrosion
      resistance and antibacterial performance. The Ti2Cu phases played an important
      role in the mechanical property and antibacterial performance for Ti6Al4V-5Cu
      alloy, and bacteria preferred to adhere on the alpha phase region, rather than
      the beta or globule Ti2Cu region.

PMID- 30274085
TI  - Towards rational design of porous nanostructured biopolymeric microparticles for
      biomacromolecules separation: A case study of intraparticle diffusion
      facilitation and BSA adsorption on agarose microspheres.
AB  - Synthesis and employing advanced materials for emerging applications is of great
      challenge for the scientific community. Recombinant proteins production and
      purification is one of the fastest growing fields in the global economy. In this
      regard, it is essential to fabricate biocompatible low-cost materials with high
      specificity to enhance purification efficiency. This requires the regulation of
      mass transfer based on the protein molecular size and interactions with the
      matrix interface; thus, needs synthesizing novel materials with tuned porosity.
      In this study, we proposed rational alteration in porous structure of
      biopolymeric microspheres using appropriate-sized porogen to facilitate
      intraparticle molecular diffusion. The tailored porous nanostructures, which were
      generated by phase separation in the polymer blend of agarose and polyethylene
      glycol, were analyzed with optical and scanning electron microscopy, Fourier
      transform infrared spectroscopy, water diffusion, and albumin adsorption. The
      well-tuned beads possessed highly porous structures with dominant mesopores owing
      to PEG phase migration out of the network. The high speed homogenizer caused an
      uncommon dense morphology with interwoven two-type porosity. Optimally tuned
      mesoporous beads with considerably high specific surface area exhibited
      dramatically fast and enhanced intraparticle diffusion of both water and protein
      molecules. Thus, the introduced porosity modification is a promising design for
      enhancing mass transfer in the bio-separation process. Finally, useful insights
      for developing future smart hydrogel microparticles with tuned porous network for
      biomolecules purification are provided by the conducted experiments.

PMID- 30274084
TI  - Effect of S60 fullerenes on the intensity of colon damage and hematological signs
      of ulcerative colitis in rats.
AB  - The application of pristine S60 fullerene aqueous colloid solution (C60FAS; 0.5
      mg/kg body weight) for rats experienced acute colitis, either intraperitoneally
      or intrarectally (1) restores the colonic mucosa healing and epithelial barrier
      integrity, evidenced by autopsies and histological findings and the normalization
      of phenolsufonphthalein dye daily excretion; (2) attenuates the consequences of
      hemorrhages, such as signs of anemia and increased platelet count; (3) improves
      the liver redox status suppressing the lipid peroxidation (malonic dialdehyde and
      protein carbonyl group levels tended down) and stimulating the antioxidant
      defense system (glutathione peroxidase activity grew up). In addition, C60FAS
      intrarectally increases the monocyte count and decreases content of neutrophil
      granulocytes, i.e. diminishes the rate of the inflammatory process and activates
      the processes of colon tissues restoring with monocytes involvement. Therefore,
      intrarectal administration of C60FAS may serve as an efficient tool of ulcerative
      colitis therapy.

PMID- 30274086
TI  - Release mechanisms of urinary tract antibiotics when mixed with bioabsorbable
      polyesters.
AB  - In depth knowledge of the thermal properties of drugs is particularly important
      when they are designed for incorporation into a thermoplastic polymer matrix. In
      this paper a representative set of Urinary Tract Infection (UTI) antibiotics were
      studied using thermogravimetric analysis (TGA) and differential scanning
      calorimetry (DSC), and then blended via solvent-casting method with poly(D,L
      lactide-co-epsilon-caprolactone). Of these, amoxicillin, cefdinir, levofloxacin
      and norfloxacin showed a co-continuous morphology with the polyester, whereas
      blends with ciprofloxacin, nitrofurantoin and tobramycin resulted in two
      immiscible phases. E. coli susceptibility results showed that the activity of
      these antibiotics was not affected by the interactions with the polymer matrix.
      The presence of the drug did not change the hydrolytic degradation kinetics of
      this fully amorphous polyester (KMw of ~0.050 days-1). However, the release
      profiles from the long-term studies (105 days) with a 10 or 30% of antibiotic
      loaded films were quite different. While water was able to penetrate the polymer
      matrix and elute the entire levofloxacin content in the first 8 h, the burst
      release of cefdinir reached a value under 75%. A more interesting profile was
      obtained with nitrofurantoin, suggesting that a lengthy treatment is achievable.
      <30% of the drug was burst released, ~55% eluted by diffusion up to day 42 and
      the rest driven by the weight loss of the bioabsorbable polyester.

PMID- 30274087
TI  - Evaluation of the corrosion inhibiting efficacy of a newly synthesized nitrone
      against St37 steel corrosion in acidic medium: Experimental and theoretical
      approaches.
AB  - A novel amphiphilic nitrone, N-phenyl-1-(4-((11-(pyridin-1-ium-1yl) undecanoyl)
      oxy)phenyl)methanimine oxide bromide (NP-1-4-11-PUOPMOB) has been synthesized
      from a fatty acid derivative as a starting material. Structural characterization
      of the new compound has been realized by spectroscopic techniques (FTIR, 1H NMR,
      and 13C NMR). The corrosion inhibition effect of the compound for St37 steel
      corrosion in 1 M HCl medium has been investigated using experimental (weight
      loss, electrochemical impedance spectroscopy, potentiodynamic polarization,
      dynamic electrochemical impedance spectroscopy) and theoretical approaches
      complemented by surface morphological examination using energy dispersive X-ray
      spectroscopy, scanning electron microscope, and atomic force spectroscopy.
      Results from both chemical and electrochemical techniques reveal that the
      presence of the nitrone in the acid solution impedes St37 steel corrosion. The
      inhibition efficiency obtained at 125 ppm and 150 ppm concentrations for all
      methods is found to be over 90%. NP-1-4-11-PUOPMOB behaves as a mixed type
      corrosion inhibitor according to the potentiodynamic polarization studies. The
      adsorption of NP-1-4-11-PUOPMOB molecules onto the metal surface follows Langmuir
      adsorption isotherm and the calculated Kads (equilibrium constant of the
      adsorption process) value reflects strong interaction. There is evidence of NP-1
      4-11-PUOPMOB adsorption on the metal surface from SEM, EDAX, and AFM studies.
      Experimental and theoretical results are in good agreement.

PMID- 30274088
TI  - Y-shaped copolymers of poly(ethylene glycol)-poly(epsilon-caprolactone) with
      ketal bond as the branchpoint for drug delivery.
AB  - In this study, a Y-shaped amphiphilic block copolymer consisting of hydrophilic
      poly(ethylene glycol) (mPEG) and two poly(epsilon-caprolactone) (PCL) as the
      hydrophobic arms with a ketal linker was synthesized (mPEG-Ketal-(PCL)2). The
      structure of the copolymer with different compositions was characterized by 1H
      NMR, gel permeation chromatography (GPC) and differential scanning calorimetry
      (DSC). The amphiphilic property endows the copolymer with the ability to be self
      assembled into micelles for encapsulating anticancer drug doxorubicin (DOX), and
      the effect of copolymer with different PCL length on drug loading properties were
      tested. The morphology, size, pH responsiveness, drug release profile and in
      vitro anticancer activity of the DOX loaded micelles were also studied. In vitro
      drug release studies showed that over 50% of the DOX was released at pH 5.0 in 24
      h because of hydrolysis of ketal linker in the copolymers. The confocal laser
      microscopy and flow cytometry experiments showed that the DOX-loaded micelles
      could be effectively internalized by Hela cells, the ketal bond in the backbone
      was broken in acid endo/lysosomal compartments and triggered the fast release of
      DOX. The in vitro antitumor efficacy of the DOX loaded mPEG-Ketal-(PCL)2 micelles
      was better than that of non-pH sensitive ones. In vivo studies showed that the
      mPEG-Ketal-(PCL)2 micelles enhanced the DOX blood circulation time and had good
      tumor-targeting efficiency.

PMID- 30274089
TI  - Corrosion and biological performance of biodegradable magnesium alloys mediated
      by low copper addition and processing.
AB  - Mg-Cu alloys were designed by introducing the well-known antibacterial property
      of copper into magnesium alloy to solve the infection problem especially under
      the neutralised environment in vitro. In this paper, the Mg-Cu alloys with
      further processing by solution and extrusion were studied to optimise the
      corrosion-related performance for their future application. It was shown that the
      differences in the property profile of Mg-Cu alloys are dependent on different
      compositions as well as on different microstructures that are obtained by the
      different processing routes. Galvanic corrosion can be significantly relieved by
      solution treatment and extrusion due to decrease and well distribution of
      cathodic Mg2Cu phases. Negligible cytotoxicity were observed with rBMSCs
      incubation. Antibacterial assays proved that the alloys reduced the viability of
      Staphylococcus aureus by high alkalinity and copper ions releasing, especially in
      comparison with pure magnesium. Finally, the as-solutionized Mg-0.1Cu alloy
      showed the optimal corrosion properties and promising antibacterial activity,
      which warranted its potentials as antibacterial biodegradable implant materials.

PMID- 30274090
TI  - Effect of UV radiation and chitosan coating on the adsorption-photocatalytic
      activity of TiO2 particles.
AB  - The effect of chitosan, pH and UV-VIS radiation on the adsorption-photocatalytic
      properties of TiO2 dispersion was investigated on the basis of electrophoretic
      mobility, as well as spectrophotometric and dynamic light scattering
      measurements. For the degradation efficiency tests two different dyes: the
      cationic - methylene blue and the anionic - sunset yellow were used. The
      stability and photodegradation experiments were performed by varying the
      parameters: wavelength of light (range 450-750 nm), type and radiation time (UV
      and VIS; 0-5 h), pH (3 and 6) and pigment concentration (0.6 * 10-5-3.6 * 10-5
      mol/dm3). In the chitosan-modified dispersions polysaccharide exhibits synergism
      of adsorption-photocatalytic properties of TiO2. Chitosan increases the
      biodegradability of the chitosan/TiO2 composite and additionally, it can be
      potentially used as a promising anti-microbial material.

PMID- 30274091
TI  - Towards wound dressings with improved properties: Effects of
      poly(dimethylsiloxane) on chitosan-alginate films loaded with thymol and beta
      carotene.
AB  - This study aimed to evaluate the effect of poly(dimethylsiloxane) on the
      mechanical properties of chitosan-alginate (CA) polyelectrolyte complexes (PECs)
      with potential application as wound dressing biomaterials. For that purpose,
      different amounts of poly(dimethylsiloxane) were incorporated during the
      formulation of the PECs. Results showed that the highest tensile strength was
      observed when using 0.1 g of poly(dimethylsiloxane) per gram of PEC (CAS10). This
      formulation was also non-hemolytic, capable of inducing thrombus formation to
      potentially reduce bleeding, and additionally presented high stability when
      exposed to physiological fluids and/or conditions simulating patient bathing. To
      improve its wound healing capacity, this formulation was loaded with thymol and
      beta-carotene (anesthetic, anti-inflammatory and antioxidant compounds) by the
      supercritical carbon dioxide impregnation/deposition (SSI/D) method at 250 bar
      and 45  degrees C for 14 h and at two depressurization rates (5 and 10 bar/min).
      The PECs were also loaded by conventional impregnation in solution for comparison
      purposes. Higher bioactive loadings, of 1.8 +/- 0.2 and 1.3 +/- 0.03 MUg per
      milligram of PEC for thymol and beta-carotene, respectively, were observed when
      using SSI/D and a higher depressurization rate (10 bar/min). These values do not
      correspond to the maximum loaded amount of each bioactive, which were strongly
      retained in the PEC structure due to favorable bioactive-polymer interactions,
      originating matrices that should present a more sustained release during in vivo
      applications.

PMID- 30274092
TI  - Composite material based on hydroxyapatite and multi-walled carbon nanotubes
      filled by iron: Preparation, properties and drug release ability.
AB  - The novel bioactive composite material based on hydroxyapatite and multi-walled
      carbon nanotubes filled by iron was synthesized by the "wet chemistry" method and
      characterized in detail by various experimental techniques including the X-ray
      diffraction, Fourier transform infrared and energy-dispersive X-ray fluorescence
      spectroscopy, thermogravimetric and differential thermal analysis. The swelling
      behaviour was quantified by measuring the changes in sample weight as a function
      of sample immersion time in a phosphate buffered saline (PBS). Bioactivity test
      was carried out by soaking the samples in PBS. The material composition influence
      on the model drug release was studied using the high-performance liquid
      chromatography method. Finally, the mechanical properties (maximal relative
      deformation, strength and Young's modulus) of the samples under loading were
      investigated too. The findings clear demonstrate the possibility of application
      of the created composite material in bioengineering of bone tissue to fill bone
      defects of various geometries with the function of prolonged release of the drug.
      It is assumed that this composite material can be used in 3D modeling of areas of
      bone tissue that have to bear a mechanical load.

PMID- 30274093
TI  - Vascular extracellular matrix and fibroblasts-coculture directed differentiation
      of human mesenchymal stem cells toward smooth muscle-like cells for vascular
      tissue engineering.
AB  - Construction of an artificial vascular graft is widely considered a promising
      strategy in vascular tissue engineering. However, limited sources of functional
      vascular smooth muscle cells (VSMCs) remain a major obstacle in vascular tissue
      engineering. In this study, we innovatively developed an approach to obtain
      functional VSMCs by onsite differentiating human bone marrow-derived mesenchymal
      stem cells (MSCs) directed by decellularized extracellular matrix (ECM) and
      fibroblasts. The resulting cells and ECM-cells constructs were characterized by
      real time RT-PCR, immunofluorescence staining, cell contractile functions, and
      migration capacity. Our results showed both ECM and fibroblasts induced MSCs
      differentiation toward VSMC-like cells with increased transcription of marker
      genes, upregulated expression of contractile apparatus proteins, and enhanced
      functional activity of VSMC phenotype. Interestingly, our findings revealed that
      native ECM and fibroblasts-coculture had a higher potential to promote MSCs
      differentiation into VSMCs than growth factors cocktail (GFC) supplemented
      culture, thereby providing a potential source of VSMCs for blood vessel
      constitution.

PMID- 30274094
TI  - Evaluation and efficacy of metal oxides in terms of antibacterial activity and
      toxic chemical degradation.
AB  - Inorganic metal oxides Ag2O, CuO and ZnO were examined using SEM, XRD, TGA and
      ICP spectroscopy to analyze their structures and physical properties in terms of
      resistance to germs and toxic chemicals. Zone of inhibition testing and the plate
      counting method were used in this study to examine the antibacterial activities
      of the metal oxides against Gram-negative Escherichia coli (E. coli) and
      Pseudomonas aeruginosa (P. aeruginosa), and Gram-positive Staphylococcus aureus
      (S. aureus) and Bacillus subtilis (B. subtilis). Furthermore, 2-chloro-ethyl
      ethyl sulfide (2-CEES) was used to study the degradation efficacy of the metal
      oxides by the NMR method. The objective of the study was to develop and evaluate
      metal oxides that are able to protect against chemical and biological warfare
      agents. Excellent antibacterial and catalytic toxic chemical degradation
      properties were obtained.

PMID- 30274095
TI  - Catalytic reduction of p-nitrophenol and methylene blue by microbiologically
      synthesized silver nanoparticles.
AB  - Catalytic Reduction of p-nitrophenol and Methylene blue by Microbiologically
      Synthesized Silver Nanoparticles was studied in the present investigation.
      Catalytic reduction of 4-Nitophenol/p-nitrophenol (PNP) and methylene blue (MB)
      was assessed using both intra and extracellular silver nanoparticles (AgNP) with
      and without immobilization. Both intracellular and extracellular AgNP were
      synthesized from actinomycetes. Antimicrobial activity of AgNP was also assessed
      and it was found that, intracellular AgNP have significant antibacterial activity
      against E. coli, S. typhi and B. subtilis. Synthesized biogenic silver
      nanoparticles were characterized by UV-visible spectrophotometry, FTIR, XRD, and
      TEM-EDS. It was found that, extracellular AgNP are efficient as compared to
      intracellular AgNP in terms of PNP reduction.

PMID- 30274096
TI  - The effect of human-like collagen calcium complex on osteoporosis mice.
AB  - The objective of this study was to assess the effect of a modified human-like
      collagen calcium complex on osteoporosis mice. BHK (Baby Hamster Kidney) cells
      were used to compare the cytotoxicity of different calcium reagents with the MTT
      test. Six-week-old male mice (n = 80) were randomly divided into eight groups: a
      blank group (blank), control group (control), human-like collagen calcium group
      (HLC-Ca), thiolated human-like collagen calcium group (SH-HLC-Ca), phosphorylated
      human-like collagen calcium group (Pi-HLC-Ca), gluconate group (Glc-Ca), calcium
      carbonate group (CaCO3) and D-cal group (B). A systematic analysis of the results
      available in vivo after 3 months of treatment was presented. The effects of
      several Ca supplements on osteoporosis mice were investigated by detecting serum
      calcium, alkaline phosphate activity (ALP), bone hydroxyproline (BHP) and bone
      mineral density (BMD). The results proved that the BMD and BHP of osteoporosis
      mice were significantly increased in the Pi-HLC-Ca group, while serum calcium and
      ALP were decreased. Therefore, Pi-HLC-Ca is likely a good calcium supplement for
      clinical applications. In this review, the advantage of Pi-HLC-Ca in preventing
      and delaying osteoporosis is highlighted. In addition to the current progress,
      further investigations are necessary to reveal the relative influences of
      collagen and calcium proportions on the long-term clinical effects of
      osteoporosis.

PMID- 30274097
TI  - Novel methods for the mechanical characterization of patches used in carotid
      artery repair.
AB  - Carotid endarterectomy (CEA) is one of the approaches available for the treatment
      of carotid artery disease, with carotid patch angioplasty the pertinent technique
      mostly preferred by vascular surgeons. This technique entails an arteriotomy
      succeeded by closure with a textile, polymer or biological tissue patch. In this
      work, we propose microbuckling and microindentation as novel methodologies for
      acquiring the mechanical properties of patches used in carotid artery repair.
      Regarding microbuckling, the patch is loaded by a sensitive dynamometer at one
      end and its motion is recorded, at three different levels of axial deformation:
      delta/l = 0.1, 0.3 and 0.5 (in the post-buckling regime). The corresponding
      experimental loads are recorded, as well. Following pertinent closed-from
      equations, various material metrics are obtained, such as the Young's modulus of
      elasticity and the so-called frictional couple of the material. Regarding
      microindentation, the material's hardness number is measured with the aid of a
      durometer. Similar to microbuckling, indentation analytical expressions allow for
      the determination of key material properties, such as the modulus of elasticity,
      indentation forces and depths. Where possible, we perform microtension to verify
      acquired results. Results demonstrate that measured properties may vary
      substantially for materials which are of the same type, due to variations of the
      material microstructure, as observed with optical and scanning electron
      microscopes (SEM). Several commercial patches were tested in this work. To
      shortly present the main results, the microbuckling technique furnished (for the
      Young's modulus) 40.17 MPa for the B/Braun Aesculap cardiovascular patch and
      71.49 MPa for the Vasutek Terumo, while the microindentation technique, for
      bovine patches, provided 6.356 MPa for the Xeno Sure and 4.701 MPa for the Vascu
      Guard. A test type recommendation is provided, relating the type of the patch
      material to the method more plausible in each case, in order to achieve better
      measurement accuracy. Results of this study can contribute in establishing
      guidelines and criteria determining material selection in CEA.

PMID- 30274098
TI  - Acute toxicity and biodistribution of different sized copper nano-particles in
      rats after oral administration.
AB  - In order to compare the detailed toxicity of nano-copper and CuCl2.2H2O (Cu ions)
      in vivo, the oral toxicity of four differently sized Cu particles (30 nm, 50 nm,
      80 nm and 1 MUm) on rats was investigated compared with CuCl2.2H2O in acute
      exposure scenarios. We compared the acute LD50 values and evaluated the kinetics
      of Cu following a single equivalent dose (200 mg/kg) of five Cu materials.
      Continuous gavage of nano-copper for 7 days, the mortality rates, relative organ
      weights, and hematological, biochemical, and histopathologic characteristics of
      rats were examined. The results showed that the LD50 values of Cu ions, 30 nm, 50
      nm, 80 nm, and 1 MUm copper particles were 359.6, 1022, 1750, 2075, and >5000
      mg/kg, respectively. Physiological and biochemical indexes indicated that 80 nm
      nano-copper (Cu NPs) produced the highest degrees of toxicity in short term. The
      liver and kidneys were the major organs most affected by Cu NPs, and also the
      target organs for Cu accumulation. The toxic effects of Cu ions are similar to
      those of nano-copper, but they were not the same. Therefore, the toxic effect of
      nano-copper is likely to be the result of the dual action of nano-copper
      particles and copper ions. Collectively, the acute toxic effects produced by Cu
      NPs were highly correlated with particle size. Moreover, the toxic effects
      produced by repeated dosing differed from those produced by a single dose, and
      this may be due to organ targeting effects that are dependent on the size of the
      nano-particles.

PMID- 30274099
TI  - Phytosynthesis of gold nanoparticles: Characterization, biocompatibility, and
      evaluation of its osteoinductive potential for application in implant dentistry.
AB  - Gold nanoparticles have been extensively used in diagnostics, biomedical imaging,
      and drug delivery owing to simple method of synthesis and versatile surface
      functionalization. Present investigation aims to evaluate the osteoinductive
      property of Salacia chinensis (SC) mediated gold nanoparticles (GNPs) for its
      application in implant dentistry. The formation of GNPs was assessed initially
      using the visual method and characterized analytically by using UV-visible
      spectroscopy, Zetasizer, X-RD, ICP-AES, AFM, and TEM. Green synthesized GNPs
      exhibited a remarkable stability in various blood components (0.2 M histidine,
      0.2 M cysteine 2% bovine serum albumin, and 2% human serum albumin) and were
      found to be nontoxic when evaluated for their cytocompatibility and blood
      compatibility using periodontal fibroblasts and erythrocytes respectively.
      Exposure of GNPs to MG-63 cell lines displayed increased percent cell viability
      (138 +/- 27.4) compared to the control group (96 +/- 3.7) which confirms its
      osteoinductive potential. Herein, it can be concluded that the stable,
      biocompatible and eco-friendly GNPs can be used as an effective bone inductive
      agent during dental implant therapy.

PMID- 30274100
TI  - Influence of the incorporation of the antimicrobial agent polyhexamethylene
      biguanide on the properties of dense and porous chitosan-alginate membranes.
AB  - This work is a continuation of a previous study which described the development
      of dense and porous chitosan-alginate polyelectrolyte complexes through the
      addition of different amounts of Pluronic F68 to the polymeric mixture. The
      present study consisted in the incorporation of an antimicrobial agent,
      polyhexamethylene biguanide (PHMB), to the previously developed system. PHMB was
      incorporated at 1 and 10% (w/w) with high incorporation efficiencies, varying
      from 72 to 86%. Release profiles in phosphate buffered saline were evaluated
      using the Korsmeyer-Peppas equation, which suggested a quasi-Fickian diffusion
      mechanism for all obtained formulations. The maximum release percentage was
      approximately 15% as a result from the high affinity between PHMB and the
      polysaccharides. The obtained polyelectrolyte complexes were able to prevent the
      growth of both Staphylococcus aureus and Pseudomonas aeruginosa on their
      surfaces, being considered potentially effective wound dressings.

PMID- 30274101
TI  - One-pot ultrafast preparation of silica quantum dots and their utilization for
      fabrication of luminescent mesoporous silica nanoparticles.
AB  - Silica quantum dots (SiQDs) and their luminescent composites have displayed great
      potential for biomedical applications owing to their chemical inert and low cost.
      In this work, we report a facile, cost-effective and ultrafast strategy to
      prepare a stable luminescent SiQDs using N-[3
      (trimethoxysilyl)propyl]ethylenediamine (EDAS) and salicylaldehyde as precursors
      for the first time. These luminescent SiQDs were further utilized for fabrication
      of luminescent mesoporous silica nanoparticles (MSNs) through direct
      encapsulation of SiQDs by MSNs. The novel synthetic and modified SiQDs uses
      commercial raw materials and the entire reaction can be completed within 30 s.
      The successful preparation of SiQDs and SiQDs@MSNs were characterized by various
      characterization equipments. The cell viability as well as cell uptake behavior
      of SiQDs@MSNs were also examined to evaluate their potential for biomedical
      applications. We demonstrated that these SiQDs@MSNs are low toxicity and of great
      potential for biological imaging. Based on the above results, we believe that
      these SiQDs@MSNs should be novel and promising candidates for biomedical
      applications owing to their intense fluorescence, biocompatibility and high
      specific surface areas.

PMID- 30274102
TI  - Nanotopographical cues of electrospun PLLA efficiently modulate non-coding RNA
      network to osteogenic differentiation of mesenchymal stem cells during BMP
      signaling pathway.
AB  - Application of stem cells in combination with nanofibrous substrates is an
      interesting biomimetic approach for enhanced regeneration of damaged tissues such
      as bone and cartilage. The investigation of the complex interplay between
      nanotopographical cues of niche and noncoding RNAs in stem cells fate is an
      effective tool to find a new strategy for enhancing the induction of
      osteogenesis. In this study, we investigated the effects of aligned and random
      orientations of nanofibers as a natural ECM-mimicking environment on the network
      of noncoding RNA in mesenchymal stem cells. Aligned and randomly oriented Ploy (L
      lactide) PLLA scaffolds were fabricated via electrospinning. Human Adipose Tissue
      Derived Mesenchymal Stem Cells (hASCs) were isolated from adipose tissue and were
      cultured on surfaces of these scaffolds. Their capacity to support hMSCs
      proliferation was also investigated by MTT assay and the expression of c-Myc
      gene. Then, after 7, 14 and 21 days, the osteogenic commitment of hMSCs and the
      miRNA regulatory network in BMP signaling pathway were evaluated by measuring
      alkaline phosphatase (ALP) activity, extracellular calcium deposition, and bone
      related gene activation by Real-Time PCR. Furthermore, osteogenic differentiation
      was evaluated with regard to their noncoding RNA network. Our results for the
      first time showed an interaction between nanotopographical cues and miRNA
      activity in hMSCs. We found that the nanotopographical cues could be used to
      influence the osteogenic differentiation process of hMSCs through the modulation
      of lncRNAs and miR-125b as negative regulators of osteogenesis as well as the H19
      modulator BMP signaling pathway that acts as a miRNA sponge. Moreover, we also
      demonstrated for the first time that MEG3 as a long noncoding RNA is controlled
      by miR-125b and microRNA-triggered lncRNA decay mechanism. This strategy seems to
      be an important tool for controlling stem cell fate in engineered tissues and
      provide new insights into most biocompatible scaffolds for bone-graft
      substitutes.

PMID- 30274104
TI  - Antimicrobial and toxicological behavior of montmorillonite immobilized metal
      nanoparticles.
AB  - With increasing demand for novel and potent antimicrobial agents to combat cross
      infections and infectious diseases, silver and copper based nanoparticles (NPs)
      deposited over supports such as montmorillonite (MMT) are playing a crucial role
      in shaping the current research scenario. Although materials based on Ag NP and
      Cu NP on MMT have been reported, its toxicological properties on human cell lines
      have not been accounted for. This paper reports a comparative study on synthesis,
      antibacterial, antifungal and toxicological behavior of Ag and Cu NPs deposited
      over MMT nanosheets synthesized by employment of different reduction media. The
      effect of synthesized NP-MMT hybrids on human erythrocytes and fibroblast cells
      has been evaluated. The NP formation was facilitated using borohydride and ethyl
      alcohol (wet chemical route) and photo-reduction and thermal treatment (physical
      reduction route). The NP-MMT hybrids showed NP formation over supporting silicate
      layers with particle size ~10-50 nm confirmed by TEM micrographs and loading of
      ~6-22 wt% of metallic element by EDX analysis. The MMT layers were peeled apart
      to accommodate NPs inside its galleries, confirmed by increased d-value in powder
      WAXD. The NP-hybrids showed excellent inhibition zone against bacteria E.coli and
      S. aureus and fungi A. niger. RBC hemolysis and cytocompatibility assay were
      performed in vitro to advocate its safety to live human cells. These hybrid
      materials are potential candidates for new generation advanced antimicrobial
      materials with less toxicity and highly potent behavior.

PMID- 30274103
TI  - Formulation, characterization, and in vitro/in vivo studies of capsaicin-loaded
      albumin nanoparticles.
AB  - Capsaicin (CAP) is a secondary metabolite with high therapeutic potential. It
      displays several bioactive properties including hypolipidemic, antioxidant, anti
      inflammatory and analgesic effects. However, CAP presents toxicity to healthy
      cells and poor pharmacokinetic profile, which is characterized by toxic
      metabolites and short half-life. In this study, CAP-loaded albumin nanoparticles
      were obtained by the desolvation-coacervation method. The preparation process was
      optimized by the application of a factorial design. Nanoparticles presented
      diameter of about 200 nm, quasi-spherical morphology, encapsulation efficiency of
      98.3 +/- 7.4%, and negative zeta potential. The in vitro release assay
      demonstrated a biphasic profile, characterized by a fast release over 12 h
      followed by a prolonged release rate. Nanoencapsulated CAP showed significant
      antioxidant activity in an in vitro assay which was concentration - and time
      dependent. In addition, the in vivo study demonstrated for the first time that
      both free and nanoencapsulated drug reduced TNF-alpha concentrations in the
      absence of inflammatory stimuli model. These novel findings indicate that albumin
      nanoparticles are potential CAP carriers and that this new drug formulation may
      be useful in several conditions, including cancer, inflammation, and neuropathic
      pain.

PMID- 30274105
TI  - Self-assembly synthesis of vapreotide-gold hybrid nanoflower for photothermal
      antitumor activity.
AB  - Based on the self-assembly properties of vapreotide acetate (Vap), one kind of
      novel vapreotide acetate-gold nanoflowers (Vap-AuNFs) was fabricated for the
      first time by biomimetic mineralization method using Vap as a template. The Vap
      AuNFs possessed anisotropic structure with a large absorption cross-section,
      which were face-centered cubic crystalline, exhibiting a remarkable monodisperse,
      narrow size (154 nm) distribution and good stability in aqueous solution. The
      apparent anisotropy of the gold nanostructure with high molar extinction
      coefficient can cause significantly higher plasmon absorption of Vap-AuNFs in the
      near infrared (NIR) region compared with Au nanoparticles (AuNPs), so the
      nanocomplex can induce remarkably enhanced photothermal conversion efficiency
      under NIR light irradiation. Breathtakingly, Vap-AuNFs exhibited superior
      biocompatibilities compared to AuNPs, as well as enhanced Hela cells lethality
      under NIR irradiation. This novel method was simple, low cost and green for the
      design and preparation of anisotropic gold nanoflowers with outstanding NIR laser
      induced local hyperthermia, highlighting their potential applications in
      biomedical fields.

PMID- 30274106
TI  - Controlled degradability of PCL-ZnO nanofibrous scaffolds for bone tissue
      engineering and their antibacterial activity.
AB  - Up to date, tissue regeneration of large bone defects is a clinical challenge
      under exhaustive study. Nowadays, the most common clinical solutions concerning
      bone regeneration involve systems based on human or bovine tissues, which suffer
      from drawbacks like antigenicity, complex processing, low osteoinductivity, rapid
      resorption and minimal acceleration of tissue regeneration. This work thus
      addresses the development of nanofibrous synthetic scaffolds of polycaprolactone
      (PCL) - a long-term degradation polyester - compounded with hydroxyapatite (HA)
      and variable concentrations of ZnO as alternative solutions for accelerated bone
      tissue regeneration in applications requiring mid- and long-term resorption. In
      vitro cell response of human fetal osteoblasts as well as antibacterial activity
      against Staphylococcus aureus of PCL:HA:ZnO and PCL:ZnO scaffolds were here
      evaluated. Furthermore, the effect of ZnO nanostructures at different
      concentrations on in vitro degradation of PCL electrospun scaffolds was analyzed.
      The results proved that higher concentrations ZnO may induce early
      mineralization, as indicated by high alkaline phosphatase activity levels, cell
      proliferation assays and positive Alizarin-Red-S-stained calcium deposits.
      Moreover, all PCL:ZnO scaffolds particularly showed antibacterial activity
      against S. aureus which may be attributed to release of Zn2+ ions. Additionally,
      results here obtained showed a variable PCL degradation rate as a function of ZnO
      concentration. Therefore, this work suggests that our PCL:ZnO scaffolds may be
      promising and competitive short-, mid- and long-term resorption systems against
      current clinical solutions for bone tissue regeneration.

PMID- 30274107
TI  - Chiral ZnO nanoparticles for detection of dopamine.
AB  - Dopamine (DA) is an important catecholamine neurotransmitter in the mammalian
      central nervous system, and is involved in many behavioral responses and brain
      functions, and thus the detection of DA is much important. Chiral nanoparticles
      (NPs) have aroused much attention and showed many potential applications. In this
      work, Chiral ZnO NPs was prepared, and the nanoparticles can disperse well
      without aggregation. The Circular dichroism (CD) test showed strong chiroptical
      signals, demonstrating it is an effect method to prepare Chiral ZnO with cysteine
      as ligand. The photoluminescent properties of Chiral ZnO was investigated and
      showed quenching effect to dopamine, which make it possible to be used as probes
      to detect dopamine in biological samples with high selectivity and sensitivity.

PMID- 30274108
TI  - Phytosynthesis of gold and silver nanoparticles enhance in vitro antioxidant and
      mitostimulatory activity of Aconitum toxicum Reichenb. rhizomes alcoholic
      extracts.
AB  - Extracts obtained from different plant species proved to be a valuable tool in
      various biomedical applications. In the same time, the phytosynthesis of noble
      metal nanoparticles represents an already well-established route for obtaining
      nanoparticles with biological activity. The present paper studies the antioxidant
      activity and the cytogenetic effects of the alcoholic extracts from rhizomes of
      Aconitum toxicum Rchb., before and after the phytosynthesis of gold and silver
      nanoparticles, on the meristematic root cells of Allium cepa L., and on the
      general mitotic index and the progression rate through the mitotic phases,
      respectively, as well as on the genetic material organized in chromosomes. The
      extracts were characterized in terms of total polyphenolics content (1.49% and,
      respectively, 2.29%) and aconitine content (by HPLC - 4.891 mg/L and,
      respectively, 18.211 mg/L), while the phytosynthesis of metallic nanoparticles
      was monitored by UV-Vis spectrometry, X-ray diffraction, X-ray fluorescence and
      electron microscopy. Both the extracts and the obtained nanoparticles were
      evaluated for antioxidant potential (the antioxidant activity ranging between 78%
      and 84.32%) and cytogenetic effects. The obtained results prove the
      phytosynthesis of AgNPs and AuNPs with dimensions ranging from 9 nm to 15 nm for
      AuNPs, respectively from 53 nm to 67 nm for AgNPs. The extracts obtained from
      rhizomes of A. toxicum Rchb. induced mitotic stress, as well as a series of
      nuclear and mitotic aberrations. The biosynthesis of AgNPs and AuNPs intensified
      the antioxidant and mitostimulatory activity of the extracts.

PMID- 30274109
TI  - Hydroxide assisted synthesis of monodisperse and biocompatible gold nanoparticles
      with dextran.
AB  - A simple and rapid approach to synthesize monodisperse and biocompatible gold
      nanoparticles (AuNPs) employing dextran as a reducing and stabilizing agents at
      different reaction conditions was described. The obtained dextran-gold
      nanoparticles (Dex-AuNPs) were characterized by transmission electron microscopy
      (TEM), UV-Vis spectroscopy, Nuclear magnetic resonance (NMR) spectroscopy,
      Fourier transformer infrared (FTIR) spectroscopy and X-ray diffraction (XRD)
      analysis. The TEM examinations showed the resultant particles were 4-50 nm in
      size, monodispersity and uniform particle size distribution. Moreover, the size
      of the nanoparticles can be controlled by varying the concentration of the
      reactants. UV-Vis spectra showed that the characteristic localized surface
      plasmon resonance (LSPR) band of AuNPs was at about 525 nm. NMR spectroscopy and
      FTIR spectroscopic analysis suggested the detailed structural information of
      dextran before and after synthesis of AuNPs. XRD and selected area electron
      diffraction (SAED) pattern analysis demonstrated that the colloidal nanoparticles
      had a well crystallized structure. The experimental analyses revealed that NaOH
      played an important role in the synthesis of Dex-AuNPs. And the possible
      formation mechanism of the fabrication of these Dex-AuNPs was also proposed. MTT
      assay was utilized to evaluate the cytotoxicity of the synthesized Dex-AuNPs on
      HeLa cells and SiHa cells. These results suggested that the prepared Dex-AuNPs
      complexes had excellent biocompatibility and acted as a candidate for further
      biomedical application.

PMID- 30274110
TI  - Ultrasound assisted reverse micelle efficient synthesis of new Ta-MOF@ Fe3O4
      core/shell nanostructures as a novel candidate for lipase immobilization.
AB  - In the present study, Ta-MOF@Fe3O4 core/shell nanostructures were synthesized in
      optimal conditions using the rapid, efficient, and novel ultrasound assisted
      reverse micelle method. FTIR, TGA/DTG, XRD, TEM, EDS and N2 adsorption/desorption
      isotherms were conducted in order to obtain samples with desirable properties.
      Results showed that the synthesized products had the thermal stability of 200 
      degrees C, particle-size distribution of 38 nm and surface area of 740 m2/g.
      Also, the VSM test showed that these compounds have desirable magnetic properties
      which provide the opportunity for recovery. Based on these obtained properties,
      final products were used as a novel candidate for enzyme immobilization. Results
      of SEM images revealed that the Bacillus licheniformis Km12 lipase is efficiently
      loaded on the Ta-MOF@Fe3O4 core/shell substrate. The stability test indicated the
      high stability of the enzyme loaded into these nanostructures. The synthesis
      method and the results obtained from enzyme immobilization developed in this
      study can be a new strategy for various applications of these novel compounds in
      diverse biological fields.

PMID- 30274111
TI  - Self-assembly of sugar based glyco-lipids: Gelation studies of partially
      protected d-glucose derivatives.
AB  - A series of sugar-based glycolipid derivatives were prepared by N-glycosylamines,
      and their organogelation property has been analyzed. We have observed the
      efficient gelation for some of the anilines substituted glycolipids derivatives
      in different aromatic and aliphatic solvents. It was found that the gelation
      occurred predominantly in aliphatic solvents with CGC of 0.8% (w/v) attributed to
      the presence of long alkyl chain in the glycolipids. The structural and
      morphological properties of the xerogels were investigated by NMR, powder XRD,
      and FE-SEM respectively. Furthermore, the thermal stability was analyzed by DSC.

PMID- 30274112
TI  - A novel cysteine-linked antibacterial surface coating significantly inhibits
      bacterial colonization of nasal silicone prongs in a phase one pre-clinical
      trial.
AB  - Ventilator associated pneumonia and sepsis are frequent complications in neonatal
      care. Bacterial colonization of medical devices and interfaces used for
      respiratory support may contribute by functioning as a bacterial reservoir
      seeding bacteria into airways. We have developed an antibacterial surface coating
      based on a cysteine ligand covalently coupled via a spacer to a carboxylic
      backbone layer on an acrylic acid grafted silicone surface. This coating was
      applied on a commercially available nasal prong and the antibacterial effect was
      evaluated both in vitro and in vivo in a first-in-human phase 1 trial. The coated
      nasal prongs had strong antibacterial activity against both Gram-negative and
      Gram-positive bacteria in vitro. In a randomized pre-clinical trial study of 24 +
      24 healthy adult volunteers who carried coated or non-coated nasal prongs for 18
      h, a 10log difference in mean bacterial colonization of 5.82 (p < 0.0001) was
      observed. These results show that this coating technique can prevent colonization
      by the normal skin and mucosal flora, and thus represent a promising novel
      technology for reduction of medical device-associated hospital acquired
      infections.

PMID- 30274113
TI  - VEGF delivery by smart polymeric PNIPAM nanoparticles affects both osteogenic and
      angiogenic capacities of human bone marrow stem cells.
AB  - OBJECTIVE: Bone tissue engineering (BTE) faces a major challenge with cell
      viability after implantation of a construct due to lack of functional vasculature
      within the implant. Human bone marrow derived mesenchymal stem cells (hBMSCs)
      have the potential to undergo transdifferentiation towards an endothelial cell
      phenotype, which may be appropriate for BTE in conjunction with the appropriate
      scaffolds and microenvironment. HYPOTHESIS AND METHODS: We hypothesized that slow
      delivery of vascular endothelial growth factor (VEGF) by using nanoparticles in
      combination with osteogenic stimuli might enhance both osteogenic and angiogenic
      differentiation of angiogenic primed hBMSCs cultured in an osteogenic
      microenvironment. Therefore, we developed a new strategy to enhance
      vascularization in BTE in vitro by synthesis of smart temperature sensitive
      poly(N-isopropylacrylamide) (PNIPAM) nanoparticles. We used PNIPAM nanoparticles
      loaded with collagen to investigate their ability to deliver VEGF for both
      angiogenic and osteogenic differentiation. RESULTS: We used the free radical
      polymerization technique to synthesize PNIPAM nanoparticles, which had particle
      sizes of approximately 100 nm at 37  degrees C and LCST of 30-32  degrees C. The
      cumulative VEGF release after 72 h for VEGF loaded PNIPAM (VEGF-PNIPAM)
      nanoparticles was 70%; for VEGF-PNIPAM loaded collagen hydrogels, it was 23%,
      which indicated slower release of VEGF in the VEGF-PNIPAM loaded collagen system.
      Immunocytochemistry (ICC) and inverted microscope visualization confirmed
      endothelial differentiation and capillary-like tube formation in the osteogenic
      culture medium after 14 days. Quantitative real-time polymerase chain reaction
      (QRT-PCR) also confirmed expressions of collagen type I (Col I), runt-related
      transcription factor 2 (RUNX2), and osteocalcin (OCN) osteogenic markers along
      with expressions of platelet-endothelial cell adhesion molecule-1 (CD31), von
      Willebrand factor (vWF), and kinase insert domain receptor (KDR) angiogenic
      markers. Our data clearly showed that VEGF released from PNIPAM nanoparticles and
      VEGF-PNIPAM loaded collagen hydrogel could significantly contribute to the
      quality of engineered bone tissue.

PMID- 30274114
TI  - Evaluation of biocompatible monomers as substitutes for TEGDMA in resin-based
      dental composites.
AB  - This works reports the synthesis and characterization of diallyl(5
      (hydroxymethyl)-1,3-phenylene) dicarbonate (HMFBA) and 5-(hydroxymethyl)-1,3
      phenylene bis(2-methylacrylate) (HMFBM) monomers and its evaluation as Bis-GMA
      eluents in the formulation of composite resins for dental use. The experimental
      materials formulated with HMFBA and HMFBM monomers presented flexural strength
      values similar to those of the control group formulated with Bis-GMA/TEGDMA.
      Regarding volumetric contraction percentage, the values obtained of experimental
      materials with HMFBA was 1.88% and for HMFBM was 4.15%, both lower than control
      resin (4.68%). In the case of double bond conversion, the resin formulated with
      HMFBA monomer exhibited a greater degree of conversion (87%). Besides, the DMA
      analyses proved that the values for Tg guarantee a good mechanical performance at
      body temperature. The new resins formulated with HMFBA and HMFBM monomers exhibit
      a cellular viability close to 100%, which indicates the absence of cytotoxicity
      towards fibroblastic cells.

PMID- 30274115
TI  - Anti-bacterial materials based on hyaluronic acid: Selection of research
      methodology and analysis of their anti-bacterial properties.
AB  - In the frame of the presented research, highly-porous structures made of
      hyaluronic acid modified with bioactive compounds were prepared. The method of
      microbiological testing of hygroscopic materials has been elaborated by
      verification of the JIS L 1902:2002 and ASTM E2149-13a test methods. The research
      has shown that the method developed in accordance with ASTM E2149-13a is suitable
      for testing the activity of hyaluronic acid samples against bacteria. E. coli and
      S. aureus. In the case of E. coli it is preferred to use as a medium the
      phosphoric buffer and for S. aureus NaCl solution from NB. By analysing the
      results of the antibacterial properties, it is important to note that the
      introduction of a small amount of zinc and zinc oxide in the matrix from the
      hyaluronic acid (in the amount of 3% by weight of the polymer) makes it possible
      to obtain a material with a strong activity against the bacterial strains. It
      enables to use this type of material as a treatment for hard-to-treat, infected
      wounds. On the other hand, using a relatively small dose of the cephalosporin
      antibiotic did not result in high levels of activity against the bacteria Gram
      "+" and Gram "-".

PMID- 30274116
TI  - Synthesis, characterization and synergistic activity of cerium-selenium
      nanobiocomposite of fungal l-asparaginase against lung cancer.
AB  - Cerium selenium nanobiocomposites are novel lung cancer drug as they possess
      combined anti-cancer property of nanocomposite with l-asparaginase working in
      synergetic manner. Cerium selenium nanobiocomposites were synthesized using
      simple co-precipitation method. The size of the nanocomposite was found to be in
      the range 60-90 nm. Maximum absorption was observed using UV spectrum in the
      range of 350-490 nm. The nanobiocomposites was characterized using H-NMR and FTIR
      analysis it was found that secondary alkyl, allylic carbon, monosubstituted
      alkenes and sp2 hybridized CH bonds of alkenes were involved in binding of cerium
      and selenium nanoparticles with l-asparaginase for the formation of cerium
      selenium nanobiocomposite. The spherical shape of the cerium selenium
      nanobiocomposites were confirmed using SEM. Anticancer activity was checked by
      performing MTT assay resulting in 70.84% and 48.78% toxicity for maximum
      concentration of 1000 (MUg/ml) and IC50 concentration of 125 (MUg/ml)
      respectively on A549 lung cancer cell line using fluorescent microscopic
      analysis.

PMID- 30274117
TI  - Biomechanical performance of hybrid electrospun structures for skin regeneration.

PMID- 30274118
TI  - Surgical repair of abdominal wall defect with biomimetic nano/microfibrous hybrid
      scaffold.
AB  - It is universal to repair abdominal wall defects with prosthetic materials in
      abdominal surgery worldwide, which are associated with high complications and
      organ damage. At present, the composite nanofibers composed of natural and
      synthetic polymers as the new type of nano structure scaffold have attracted
      considerable attention in the field of tissue engineering. In this study we
      examined the feasibility of using electrospun silk fibroin (SF)/poly (3
      hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) hybrid scaffolds for repairing of
      abdominal wall defects. Both in vivo and in vitro characterization were evaluated
      to access efficacy of the nanofiber for tissue regeneration. Our results showed
      that the electrospun SF/PHBV nanofiber scaffolds could stimulate the expression
      of TGF-beta1 and Collagen I in fibroblasts in vitro and then promote granulation
      and connective tissue depositions, but not result in a strong foreign body
      reaction in vivo. Moreover, we conjectured the potential molecular biological
      mechanism of SF/PHBV hybrid scaffolds in the process of tissue regeneration.
      Thus, the SF/PHBV hybrid nanofiber scaffolds have high efficiency and
      biocompatibility to repair abdominal wall defects.

PMID- 30274119
TI  - One-step fabrication and characterization of Fe3O4/HBPE-DDSA/INH nanoparticles
      with controlled drug release for treatment of tuberculosis.
AB  - In this study, Fe3O4/hyperbranched polyester-(2-dodecen-1-yl)succinic anhydride2
      Dodecen-1-/isoniazid magnetic nanoparticles (Fe3O4/HBPE-DDSA/INH MNPs) with
      controlled drug release characteristics were synthesized successfully by a simple
      one-step method. Orthogonal experiments were performed to optimize the loading
      capacity and encapsulation efficiency of the MNPs. The structure of the
      Fe3O4/HBPE-DDSA/INH MNPs was characterized by 1H nuclear magnetic resonance
      spectroscopy, matrix-assisted laser desorption/ionization mass spectrometry,
      Fourier transform infrared spectroscopy, X-ray diffraction analysis, transmission
      electron microscopy, and superconducting quantum interference device
      measurements, while their properties were characterized based on swelling
      behavior observations, in-vitro release experiments, and cytotoxicity analysis.
      The results indicated that the fabricated Fe3O4/HBPE-DDSA/INH MNPs had a high
      drug-loading capacity and encapsulation efficiency. Further, the drug-release
      rate of the MNPs was higher in an acidic buffer, indicating that the MNPs were pH
      responsive. Swelling studies revealed that the MNPs exhibited diffusion
      controlled drug release, while in-vitro release studies revealed that the drug
      release properties could be controlled readily, owing to the high encapsulation
      efficiency of the MNPs and the uniform dispersion of the drug in them. These
      results collectively suggest that this multifunctional nontoxic drug delivery
      system, which exhibits good magnetic properties and pH-triggered drug-release
      characteristics, should be suitable for the treatment of tuberculosis.

PMID- 30274120
TI  - Effects of gallic acid biofabricated rGO nanosheets combined with radiofrequency
      radiation for the treatment of renal cell carcinoma.
AB  - The combination of biologically active compounds and nanomaterials in biomedicine
      field is growing rapidly and provided excellent forecasts for the progress of
      facile non-invasive approaches for the diagnosis of cancer therapy. In this
      present study, we demonstrated that as-prepared gallic acid (GA) coated reduced
      graphene oxide (rGO) combined with radiofrequency (RF) ablation has facilitated
      for the treatment of human renal epithelial cancer (A-489) cells without
      disturbing the renal proximal epithelial (HK-2) cells. The successful
      biofabrication of GA onto the rGO nanostructure has been elaborated with the
      support of peak intensities of diffracted X-ray patterns and Raman spectral
      visualizations. The micrograph imageries are displayed that the warped and ribbed
      structure containing wrinkled paper-like arrangement with multilayer structure of
      rGO with assistance of GA molecules. The synthesized GA-rGO nanomaterials
      exhibited a very good apoptosis and toxic effect on A-489 renal cancer cells,
      which was found to exhibit enhanced tumor cytotoxicity in RF combination
      treatment compared to RF treated alone. Moreover, the results are highly cheering
      to go for functionalized nanomaterial and RF radiation, combined drug delivery
      system to overcome the limitation to treat kidney cancers.

PMID- 30274121
TI  - Effects of graphene on the structure, properties, electro-response behaviors of
      GO/PAA composite hydrogels and influence of electro-mechanical coupling on BMSC
      differentiation.
AB  - Electro-responsive Graphene oxide-poly(acrylic acid) (GO-PAA) nanocomposite
      hydrogels with different concentrations of GO were successfully fabricated via in
      situ polymerization. The covalently crosslinked PAA network is intertwined with
      GO sheets by the bridging of hydrogen-bond interactions thus resulting in an
      integrated and stable hydrogel network. The swelling, mechanical and conductivity
      properties of the hydrogel are impacted as a result. The influences of different
      factors on the electro-response behavior of the hydrogels were deeply explored.
      Because of electrostatic double layer of the GO, the response properties of
      hydrogels in different voltage, pH, and ionic strength improved significantly.
      Meanwhile, with the addition of GO, the response performance of hydrogel in
      biological applications was greatly expanded. Furthermore, GO-PAA hydrogel shows
      a good compatibility with bone marrow-derived mesenchymal stem cells (BMSCs). The
      electro-mechanical coupling of the hydrogel can change the morphology of the
      adhesive cells, and regulate the cytoskeleton of the cell under the condition of
      electrical stimulation, which can further promote the differentiation of neural
      stem cells. This electro-responsive hydrogel could be widely used in many fields
      of biomedical application such as artificial muscle and tissue engineering
      scaffold.

PMID- 30274122
TI  - Novel core-shell dextran hybrid nanosystem for anti-viral drug delivery.
AB  - Zidovudine (AZT) is an antiviral drug extensively used for combating the global
      pandemic- HIV/AIDS. However, its uses are overshadowed by its short half -life,
      poor aqueous solubility and inability to cross physiological barriers. This study
      highlights a nanosystem consisting of dextran and stearic acid for AZT delivery.
      This hybrid nanoparticle was prepared by double emulsion solvent evaporation
      method. The morphological analysis of the prepared nanoparticles was carried out
      by transmission electron microscopy (TEM) and structural analysis through FTIR
      spectroscopy. Haemolysis, blood cell aggregation and cytotoxicity evaluations
      were also performed. These biological evaluations indicated that the
      nanoparticles were compatible and fluorescence microscopy studies demonstrated
      increased cellular internalization of drug loaded hybrid nanoparticles when
      compared with free drug molecules. The experimental outcomes indicate that the
      prepared nanoparticles are highly biocompatible haemocompatible and effective in
      getting internalized into cells of neural origin. These results highlight the
      feasibility and efficacy of the hybrid nanoparticles for effective delivery of
      zidovudine.

PMID- 30274123
TI  - "The return of ceramic implants": Rose stem inspired dual layered modification of
      ceramic scaffolds with improved mechanical and anti-infective properties.
AB  - Nowadays, traditional ceramics for bone implants have considerably replaced by
      metal based biomedical materials, attributing to the friability of ceramics.
      However, ceramic implants possess excellent biocompatibility and longtime
      abrasion resistance. They should be more desirable for long-term uses of implants
      in case their fragility had been overcome. In the present work, inspired from
      natural rose, a dual-layer-modified ceramic scaffold was constructed by coating a
      superplastic layer of isocyanate (ISO) resin and a nano Zinc Oxide (nano-ZnO)
      layer on the ceramic scaffold. The ISO resin modification layer with 1 mm
      thickness, improved the mechanical properties of ceramic implants 2-3 times, and
      protect the ceramic implants from broken even drop from 1 m high. Moreover, such
      dual layered modification exhibited broad spectrum antibacterial behavior. In
      vivo biocompatible studies demonstrated that there was no obvious noticeable
      tissue damage in all major organs of mice after the implant surgeries.

PMID- 30274124
TI  - Tuneable hydrogels of Caf1 protein fibers.
AB  - Capsular antigen fraction 1 (Caf1) is a robust polymeric protein forming a
      protective layer around the bacterium Yersinia pestis. Occurring as ~1 MUm
      polymeric fibers, it shares its immunoglobulin-like fold with the majority of
      mammalian extracellular proteins such as fibronectin and this structural
      similarity suggests that this unusual polymer could form useful mimics of the
      extracellular matrix. Driven by the pressing need for reliable animal-free 3D
      cell culture environments, we showed previously that recombinant Caf1 produced in
      Escherichia coli can be engineered to include bioactive peptides, which influence
      cell behavior. Here, we demonstrate that through chemical crosslinking with a
      small palette of PEG-based crosslinkers, Caf1-based hydrogels can be prepared
      displaying a wide range of mechanical and morphological properties that were
      studied by rheology, compressive testing, SDS-PAGE and scanning electron
      microscopy. By varying the Caf1 protein concentration, viscoelasticity and
      stiffness (~11-2300 Pa) are reproducibly tunable to match natural and commercial
      3D gels. Hydrogel porosity and swelling ratios were found to be defined by
      crosslinker architecture and concentration. Finally the hydrogels, which are 95
      99% water, were shown to retain the high stability of the native Caf1 protein in
      a range of aqueous conditions, including extended immersion in cell culture
      media. The unusual Caf1 polymer thus offers the possibility of presenting
      bioactive protein subunits in a precisely tuneable hydrogel for use in cell
      culture and drug delivery applications.

PMID- 30274125
TI  - A novel gold-based stimuli-responsive theranostic nanomedicine for chemo
      photothermal therapy of solid tumors.
AB  - The chemo-photothermal therapy performance of a novel theranostic nanoparticles
      that fabricated through the conjugation of HS-poly(epsilon-caprolactone)-block
      poly(N-isopropylacrylamide)-block-poly(acrylic acid) (HS-PCL-b-PNIPAAm-b-PAA) and
      gold nanoparticles (GNPs) was extensively investigated. The GNPs@polymer
      conjugate theranostic NPs was loaded with doxorubicin hydrochloride (DOX) as an
      anticancer drug through electrostatic interactions to afford GNPs@polymer-DOX
      theranostic nanomedicine. Temperature and pH-triggered in vitro drug release
      behavior of the developed theranostic nanomedicine were also examined. The
      biocompatibility of the synthesized GNPs@polymer theranostic NPs was confirmed
      through the assessing survival rate of breast cancer cell line (MCF7) using MTT
      assay. In vitro cytotoxic effects of the GNPs@polymer-DOX theranostic
      nanomedicine was also evaluated against MCF7 cells in both with or without laser
      irradiation (532 nm, 145 mJ per pulse, 5 min) conditions, and the results
      obtained were compared with free DOX as the reference. As the results, the
      developed GNPs@polymer-DOX can be considered as theranostic nanomedicine for
      chemo-photothermal therapy of solid tumors.

PMID- 30274126
TI  - 3D culture of neural stem cells within conductive PEDOT layer-assembled
      chitosan/gelatin scaffolds for neural tissue engineering.
AB  - Neural stem cells (NSCs), as a self-renewing and multipotent cell population,
      have been widely studied for never regeneration. Engineering scaffold is one of
      the important factors to regulate NSCs proliferation and differentiation towards
      the formation of the desired cells and tissues. Because neural cells are electro
      active ones, a conductive scaffold is required to provide three-dimensional cell
      growth microenvironments and appropriate synergistic cell guidance cues. In this
      study, a poly (3,4-ethylenedioxythiophene)/chitosan/gelatin (PEDOT/Cs/Gel)
      scaffold was prepared via in situ interfacial polymerization, with a
      nanostructured layer of PEDOT assembling on the channel surface of porous Cs/Gel
      scaffold. This electrically conductive, three-dimensional, porous and
      biodegradable PEDOT/Cs/Gel scaffold was used as a novel scaffold for NSCs three
      dimension (3D) culture in vitro. It was found that the layer of PEDOT on the
      channel surface of Cs/Gel scaffolds could greatly promote NSCs adhesion and
      proliferation. Additionally, under the differentiation condition, the protein and
      gene analysis suggested that PEDOT/Cs/Gel scaffolds could significantly enhance
      the NSCs differentiation towards neurons and astrocytes with the up-regulation of
      beta tubulin-III and GFAP expression. In conclusion, these results demonstrated
      that the PEDOT/Cs/Gel scaffolds as an electrically conductive scaffold could not
      only promote NSCs adhesion and proliferation but also enhance NSCs
      differentiation into neurons and astrocytes with higher protein and gene
      expression. PEDOT-assembled Cs/Gel scaffold will be a promising conductive
      substrate for NSCs research and neural tissue engineering.

PMID- 30274127
TI  - A water-soluble silver(I) formulation as an effective disinfectant of contact
      lenses cases.
AB  - The antibacterial effect of the already known water-soluble compound {[Ag6(MU3
      Hmna)4(MU3-mna)2]2-.[(Et3NH)+]2.(DMSO)2.(H2O)} (AGMNA) (H2mna = 2-mercapto
      nicotinic acid) was evaluated by the mean of the Minimum Inhibitory Concentration
      (MIC), the Minimum Bactericidal Concentration (MBC) and the Inhibitory Zone (IZ),
      against the bacterial strains Pseudomonas aeruginosa (PAO1) and Staphylococcus
      aureus (St. aureus) which settle in the cornea, in bacterial keratitis. The MICs'
      of AGMNA against PAO1 and St. aureus were 25.7 +/- 2.4 MUM and 42.0 +/- 0.3 MUM
      respectively. Tauhe Biofilm Elimination Concentration (BetaEpsilonC) was used to
      evaluate the influence of AGMNA on the formation of biofilm of PAO1. AGMNA
      exhibits stronger antimicrobial activity than that of H2mna or AgNO3. The
      toxicity of AGMNA was examined against normal human corneal epithelial cells
      (HCET cells) and by micronucleus (MN) assay in HCET cells. Thus, the IC50 value
      of AGMNA, towards HCET cells is higher than 120 MUMU, while its effect on MN
      frequency, of HCET cells, is meaningless, when they are treated with it at 120
      MUMU, suggesting no in vitro genotoxicity. The Mitotic Index (MI), Chromosomal
      Aberrations (CA) and Nuclear Abnormalities (NA) analyses of Allium cepa reveal
      insignificant variations between treated and untreated ones indicating no in vivo
      genotoxicity.

PMID- 30274128
TI  - Corrosion behaviour and cell interaction of Ti-6Al-4V alloy prepared by two
      techniques of 3D printing.
AB  - 3D printing seems to be the technology of the future for the preparation of
      metallic implants. For such applications, corrosion behaviour is pivotal.
      However, little is published on this topic and with inconsistent results.
      Therefore, we carried out a complex study in which we compared two techniques of
      the 3D printing technology - selective laser melting and electron beam melting.
      The corrosion behaviour was studied in physiological solution by standard
      electrochemical techniques and susceptibility to localised corrosion was
      estimated too. All samples showed typical passive behaviour. Localised corrosion
      was shown to be possible on the original as-printed surfaces. Corrosion
      experiments were repeated tree times. To reveal possible negative effects of 3D
      printing on cytocompatibility, direct in vitro tests were performed with U-2 OS
      cells. The cells showed good viability and proliferation, but their growth was
      impeded by surface unevenness. Our results suggest that both techniques are
      suitable for implants production. Statistical evaluation was performed by ANOVA
      followed by Tukey's test.

PMID- 30274129
TI  - Triclosan loaded polyurethane micelles with pH and lipase sensitive properties
      for antibacterial applications and treatment of biofilms.
AB  - Three different kinds of polyurethane (PU) micelles, i.e. PEG-c-PU, PEG-g-PU and
      PEG-b-PU, with hydrophobic PCL core and hydrophilic PEG corona were prepared by
      self-assembly method. DLS studies illustrated that PEG-g-PU micelles showed pH
      dependent surface charge switching properties while no obvious surface charge
      switching activities were found for PEG-b-PU and PEG-c-PU micelles. Triclosan was
      loaded into PCL core by dialysis method with pretty high encapsulate content and
      efficiency and the payloads were released at an accelerate rate in the presence
      of lipase. MIC and MBC studies demonstrated an enhanced antibacterial activity of
      encapsulated Triclosan against planktonic bacteria than free Triclosan. CLSM
      images of S. aureus biofilms treated with Nile red loaded PU micelles illustrated
      the penetration and accumulation of PEG-g-PU micelles inside the bacterial
      biofilms at an acidic environment. In addition, Triclosan loaded into PEG-g-PU
      micelles showed more potent antibiofilm activities than that loaded into PEG-c
      PEG and PEG-b-PU micelles. Therefore, the PEG-g-PU micelles can be potentially
      used as hydrophobic antibiotic carriers to treat bacterial infections and
      biofilms.

PMID- 30274130
TI  - Antibacterial dental adhesive resins containing nitrogen-doped titanium dioxide
      nanoparticles.
AB  - : The development of dental adhesive resins with long-lasting antibacterial
      properties is a possible solution to overcome the problem of secondary caries in
      modern adhesive dentistry. OBJECTIVES: (i) Synthesis and characterization of
      nitrogen-doped titanium dioxide nanoparticles (N_TiO2), (ii) topographical,
      compositional and wettability characterization of thin-films (unaltered and
      experimental) and, (iii) antibacterial efficacy of N_TiO2-containing dental
      adhesives against Streptococcus mutans biofilms. MATERIALS AND METHODS:
      Nanoparticles were synthesized and characterized using different techniques.
      Specimens (diameter = 12 mm, thickness ? 15 MUm) of OptiBond Solo Plus (Kerr
      Corp., USA) and experimental adhesives [50, 67 and 80% (v/v)] were fabricated,
      photopolymerized (1000 mW/cm2, 1 min) and UV-sterilized (254 nm, 800,000 MUJ/cm2)
      for microscopy, spectroscopy, wettability and antibacterial testing. Wettability
      was assessed with a contact angle goniometer by dispensing water droplets (2 MUL)
      onto four random locations of each specimen (16 drops/group). Drop profiles were
      recorded (1 min, 25 frames/s, 37  degrees C) and contact angles were calculated
      at time = 0 s (thetaINITIAL) and time = 59 s (thetaFINAL). Antibacterial testing
      was performed by growing S. mutans (UA159-ldh, JM10) biofilms for either 3 or 24
      h (anaerobic conditions, 37  degrees C) with or without continuous light
      irradiation (410 +/- 10 nm, 3 h = 38.75 J/cm2, 24 h = 310.07 J/cm2) against the
      surfaces of sterile specimens. RESULTS: N_TiO2 was successfully prepared using
      solvothermal methods. Doped-nanoparticles displayed higher light absorption
      levels when compared to undoped titania. Experimental adhesives demonstrated
      superior antibacterial efficacy in dark conditions. CONCLUSIONS: The findings
      presented herein suggest that N_TiO2 is a feasible antibacterial agent against
      cariogenic biofilms.

PMID- 30274131
TI  - Effect of heat-transfer capability on micropore structure of freeze-drying
      alginate scaffold.
AB  - Biodegradable porous scaffold is widely used in the field of tissue engineering.
      Scaffolds were required to have proper microstructure with suitable size,
      gradient, shape and porosity to mimic the specific three-dimensional structure of
      extracellular matrix. Taken the simple technique of freeze-drying, the nucleation
      and growth of ice crystals were affected by thermal behavior of solution during
      freezing process, which could be controlled to tailor and predict the pore
      structure in scaffold. This paper aimed to reveal the effect of containers' heat
      transfer capability on the thermal behaviors of solution, and then its influence
      to pore structure in scaffold. Four containers with different heat transfer
      capacity were adopted for cooling model to achieve different thermal
      characterizations within solution during cooling process. The vertical cross
      section of scaffold was observed by scanning electron microscopy. The porosity
      and tensile properties of scaffold were measured to depict scaffold
      characteristics. Scaffolds fabricated by containers with lambda/d = 20,000, 3000
      and 450 W/m2. degrees C showed cellular pores with gradient. With the decrease of
      lambda/d, pores in scaffold were enlarged, and the wall between neighboring pores
      also became thicker. Pillared pores were produced only in container with lambda/d
      = 50 W/m2. degrees C, oriented along the vertical direction without gradient.
      This process demonstrated that by altering the container of cooling model,
      scaffold microstructure could be tailored.

PMID- 30274132
TI  - Multifunctional polymer coatings for titanium implants.
AB  - The aim of this work was to modify the surface of the titanium implants by
      application of multifunctional polymer coatings based on polyurethane and its
      composites with graphene and beta-TCP. Graphene was used as an antibacterial
      agent, TCP as a bioactive component, and polymer coating as a corrosion
      protection of metal. As a result, materials with different surface
      characteristic, from hydrophilic to hydrophobic, varying in bioactivity and
      biocompatibility, were obtained. Wettability of the materials was tested by the
      sessile drop method; surface roughness was assessed on the basis of Ra parameter,
      measured by contact profilometry. The surface characteristic was complemented by
      microhardness testing. Also, in vitro immersion tests in fluids and cell tests
      were performed. Obtained results suggest that it is possible to fabricate, on the
      surface of titanium implants, multifunctional composite coatings based on
      polyurethane, with optimal composition for bone surgery and dentistry
      applications. The study further showed that the chemical structure (composition)
      of the polymer and the graphene content are crucial in terms of biocompatibility
      of the final material, while addition of tricalcium phosphate affects its
      bioactivity.

PMID- 30274133
TI  - High toxicity of Bi(OH)3 and alpha-Bi2O3 nanoparticles towards malignant 9L and
      MCF-7 cells.
AB  - Here we report the extreme toxicity in vitro of Bi(OH)3 and alpha-Bi2O3
      nanoparticles (NPs), obtained through a facile synthesis with an average single
      particle size of 6-10 nm, tested on malignant gliosarcoma 9L and MCF-7 human
      breast cancer cells. For both nanomaterials, clonogenic assays reveal a mortality
      of over 90% in 9L and MCF-7 cells for a concentration of 50 MUg/mL after
      incubation for 24 h. Moreover, the NPs show a significant mortality of up to 60%
      in the malignant cells at the very low concentration of 6.25 MUg/mL. In contrast,
      at the same concentration, the nanomaterials exhibit no noticeable mortality
      towards normal Madin-Darby canine kidney cells. The internalisation of the NPs
      was demonstrated using flow cytometry and confocal microscopy was used to
      investigate when the loss of cell viability starts. The NPs show a faster cell
      death in 9L cells compared with MCF-7 cells, demonstrated via the identification
      of apoptosis through increased sub G1 levels after 24 h of NP incubation.
      Cleavage is identified as the main apoptotic nuclear morphology in 9L, which
      suggests the presence of reactive oxygen species.

PMID- 30274134
TI  - Facile incorporation of REDV into porous silk fibroin scaffolds for enhancing
      vascularization of thick tissues.
AB  - Rapid neovascularization within scaffolds is critical for the regeneration of
      thick complex tissues. The surface immobilization of peptides and other active
      molecules have been explored to improve the vascularization capacity of implants.
      However, the rapid degradation of these molecules, the reaction conditions and
      cross-linking usually result in decreased vascularization capability. Here, we
      introduced a temperate, all-aqueous process to achieve bulk porous silk fibroin
      (SF) scaffolds. A temperature controlled process was used to induce the water
      stable structure by SF self-assembly. Arg-Glu-Asp-Val (REDV) peptides were added
      into SF solution and fixed within SF scaffolds during the self-assembly process.
      The results showed that the functionalized scaffolds markedly promoted the
      adhesion of endothelial cells in vitro. Moreover, the in vivo studies indicated
      enhanced cell infiltration in the bulk functionalized SF scaffolds and impressive
      vascularization at 4 weeks post-implantation. The functionalized scaffolds
      demonstrated excellent vascularization capability, providing an exciting
      biomaterial option for thick tissue regeneration.

PMID- 30274135
TI  - Aminopeptidase N (CD13) targeted MR and NIRF dual-modal imaging of ovarian tumor
      xenograft.
AB  - The development of tumor-specific imaging nanoprobes with the potential to
      improve the accuracy of cancer diagnosis has become an area of intense research.
      Aminopeptidase N (CD13) predominantly expresses on the surface of ovarian tumor
      cells and can be specifically recognized by Asn-Gly-Arg (NGR) peptide. The
      applicability of CD13 as a target for specific ovarian tumor imaging, however,
      remains unexploited so far. In this study, Cy5.5-labeled, NGR-conjugated iron
      oxide nanoparticles (Cy5.5-NGR-Fe3O4 NPs) were prepared as an ovarian tumor
      specific bimodal imaging nanoprobe. It is demonstrated that the conjugation of
      NGR targeting moiety leads to a higher cellular uptake toward ES-2 cells, the
      human ovarian carcinoma cells that highly express CD13. Moreover, magnetic
      resonance imaging of ovarian tumor xenograft reveals that the Fe3O4-Cy5.5-NGR NPs
      results in a significant T2* signal reduction in the tumor. Meanwhile, near
      infrared fluorescence imaging indicates a higher accumulation of Fe3O4-Cy5.5-NGR
      NPs in the tumor xenograft. Therefore, CD13 could be applied as a novel and
      efficient target for constructing ovarian tumor specific nanoprobes with improved
      accuracy for ovarian tumor diagnosis.

PMID- 30274137
TI  - In-vitro and in-vivo, cytotoxicity evaluation of cast functionally graded
      biomaterials for dental implantology.
AB  - An innovative technique of casting the titanium implant alloys and its calcium
      phosphate coating using centrifugal casting method was proposed in the current
      study. This one-step, self-coating technique results in formation of functionally
      graded biomaterials (FGBMs) of calcium phosphate/Titanium alloys. Two groups of
      samples (Group 1 and Group 2) were prepared utilizing self-coated titanium
      niobium (Ti-6Al-7Nb) and titanium- vanadium (Ti-6Al-4V) alloys respectively. The
      cast samples were then prepared for in-vitro cytocompatibility evaluation, in
      vivo systemic toxicity and osseointegration evaluation. Cytocompatibility was
      examined in-vitro on human bone osteosarcoma cells (Saos-2). In-vivo surgical
      implantation of the samples in the mandible of the experimental dogs was
      correspondingly implemented. Tests for systemic toxicity, X-ray images, Dual
      Energy X-ray Absorptiometry (DEXA) and histopathological analysis were obtained
      for each dog's mandible sample. In-vitro cytocompatibility studies revealed high
      cytocompatibility of Group 2 in comparison to Group 1. In-vivo results proved
      safety of Group 2 as regards to systemic toxicity. On the other hand, results of
      the X-ray images, DEXA and histopathological analysis revealed comparable
      osseointegration potential of both groups. These results suggest the use of
      Group2-FGBMs in dental implant manufacturing and prove that FGBMs prepared by
      centrifugal casting as self-coated implants have good biocompatibility and
      osseointegration capability.

PMID- 30274136
TI  - Development of three-dimensional printing polymer-ceramic scaffolds with enhanced
      compressive properties and tuneable resorption.
AB  - In this study, bone tissue engineered scaffolds fabricated via powder-based 3D
      printing from hydroxyapatite (HA) and calcium sulphate (CaSO4) powders were
      investigated. The combination of using a fast resorbing CaSO4 based powder and
      the relatively slower HA powder represents a promising prospect for tuning the
      bioresorption of 3D printed (3DP) scaffolds. These properties could then be
      tailored to coincide with tissue growth rate for different surgical procedures.
      The manufactured scaffolds were infiltrated with poly(epsilon-caprolactone)
      (PCL). The PCL infiltrated the inter-particle spacing within the 3DP structures
      due to the nature of a loosely-packed powder bed and also covered the surface of
      ceramic-based scaffolds. Consequently, the average compressive strength,
      compressive modulus and toughness increased by 314%, 465% and 867%, respectively.
      The resorption behaviour of the 3DP scaffolds was characterised in vitro using a
      high-throughput system that mimicked the physiological environment and dynamic
      flow conditions relevant to the human body. A rapid release of CaSO4 between Day
      0 and 28 was commensurate with a reduction in scaffold mass and compressive
      properties, as well as an increase in medium absorption. In spite of this, HA
      particles, connected by PCL fibrils, remained within the microstructure after 56
      days resorption under dynamic conditions. Consequently, a high level of
      structural integrity was maintained within the 3DP scaffold. This study presented
      a porous PCL-HA-CaSO4 3DP structure with the potential to encourage new tissue
      growth during the initial stages of implantation and also offering sufficient
      structural and mechanical support during the bone healing phase.

PMID- 30274138
TI  - Photoactivated water-disinfecting, and biological properties of Ag NPs@Sm-doped
      ZnO nanorods/cuttlefish bone composite: In-vitro bactericidal, cercaricidal and
      schistosomicidal studies.
AB  - Herein, eco-friendly composite was synthesized by embedding silver (Ag)
      nanospheres onto aragonitic cuttlefish bone (CB)-stabilized samarium doped zinc
      oxide (Sm-doped ZnO) nanorods. The operating interaction profile and the
      photoactive behavior of this nanocomposite were assessed via XRD, FTIR, Raman,
      TEM, FE-SEM, DLS, DRS and PL techniques. Locality of Sm-doped ZnO and its
      attaching modes to the cuttlefish bone lamella were highly dominated by embedding
      Ag NPs that encouraged Zn2+ Lewis acid sites to electrostatically interact with
      aragonite carbonates in the channeled porous CB system. Such interacting approach
      enhanced photoactivity of Sm-doped ZnO by lowering its energy band gap (from 3.26
      eV for Sm-doped ZnO/CB to 2.12 eV for Ag@Sm-doped ZnO/CB). Besides, plasmon
      induced silver electrons provided Sm-doped ZnO by extra photosensitivity. Ag@Sm
      doped ZnO/CB nanocomposite exhibited pronounced photo-activated disinfection
      efficiencies for Staphylococcus aureus (80%), Pseudomonas aeruginosa (60%), and
      Schistosoma mansoni cercariae (100%) linked with progressive demolition in
      cercarial body. Such nanocomposite also possessed exterminating action against
      Schistosoma mansoni adult worms serving near 100% worm-mortality accompanied by
      significant disintegration of worm body. These findings were successfully drawn
      Ag@Sm-doped ZnO/CB as an efficient weapon in the biocides arsenal being even
      capable of destructing pathogenic bacteria and parasites in dark- and photo-
      conditions.

PMID- 30274139
TI  - Investigation on Task Shifting of HIV/AIDS Follow-Up Management Workers in New
      Launched Areas, China.
AB  - Background: This study aimed to understand attitudes of HIV/AIDS follow-up
      workers regarding task shifting, reveal the current conditions of this
      implementation, as well as to find out any challenges of early-stage
      implementation. Methods: Taking Jiangxi Province as an example, a cross-sectional
      survey with 102 health professionals in CDCs (Centers for Disease Control and
      Prevention) and 92 health care providers in primary health institutions was
      conducted from November 2016 to January 2017. This survey includes the
      demographic backgrounds of participants, their attitudes towards task shifting,
      and the main difficulties faced in their work, etc. Results: 60.8% of
      professionals and 77.2% of providers hold positive attitudes towards task
      shifting. Both health professionals and providers express their concerns about
      unclear and undefined funds distribution and lack of confidentiality of PLWHA
      (people living with HIV) in local primary health institutions. Conclusions: The
      majority of health workers hold positive attitudes towards task shifting. It also
      highlights some negative reactions in implementation, and reveals the main
      difficulties that constitute barriers to follow-up. Findings from this study may
      provide evidence for enhancing future implementation of task shifting.

PMID- 30274140
TI  - Subchronic Toxicity Studies of Cortex Dictamni Extracts in Mice and Its Potential
      Hepatotoxicity Mechanisms in Vitro.
AB  - Cortex Dictamni is a commonly-used traditional Chinese herbal medicine for the
      treatment of skin inflammation, tinea, and eczema. Recently, some studies
      reported that Cortex Dictamni might induce liver injury, suggesting more
      attention to its safety. The current study was designed to investigate subchronic
      toxicity of Cortex Dictamni aqueous extract (CDAE) and ethanol extract (CDEE) in
      mice and the potential hepatotoxicity mechanisms in vitro. Firstly, CDAE or CDEE
      groups were administrated with varying dosages (2.3, 4.6, or 9.2 g/kg/day, p.o.)
      in mice for 28 days in subchronic toxicity studies. General clinical signs and
      biochemical parameters were examined, and morphological analyses were conducted.
      Secondly, we identified the different constituents of CDAE and CDEE using HPLC
      MS/MS and chose major components for further study. In order to determine the
      toxic components, we investigated the cytotoxicity of extracts and chosen
      components using CCK-8 assay in HepG2 cells. Furthermore, we explored the
      possible hepatotoxicity mechanisms of Cortex Dictamni using a high content
      analysis (HCA). The results showed that no significant differences of general
      clinical signs were observed in mice. Aspartate alanine aminotransferase (ALT)
      and aminotransferase (AST) were significantly increased in the high-dose CDAE and
      CDEE groups compared to the control group. Meanwhile, the absolute and relative
      liver weights and liver/brain ratio were significantly elevated, and histological
      examination of liver demonstrated cellular enlargement or nuclear shrinkage. In
      UPLC analysis, we compared the chemical constituents between CDAE and CDEE, and
      chose dictamnine, obakunone, and fraxinellone for hepatotoxicity evaluation in
      the in vitro studies. In the CCK-8 assay, CDAE, CDEE, dictamnine, obakunone, and
      fraxinellone decreased the cell viability in a dose-dependent manner after
      treatment for 48 h. Furthermore, the cell number decreased, while the nuclear
      intensity, cell membrane permeability, and concentration of reactive oxygen
      species were shown to increase, meanwhile, mitochondrial membrane potential was
      also changed in HepG2 cells following 48 h of compounds treatment using HCA. Our
      studies suggested that CDAE and CDEE have potential hepatotoxicity, and that the
      alcohol extraction process could increase toxicity. Dictamnine, obakunone, and
      fraxinellone may be the possible toxic components in Cortex Dictamni with
      dictamnine as the most potentially hepatotoxic component, whose potential
      hepatotoxicity mechanism may be associated with cell apoptosis. Moreover, this
      study could provide valuable data for clinical drug safety research of Cortex
      Dictamni and a good example for safety study of other Chinese herbal medicines.

PMID- 30274141
TI  - Health and Well-Being of Cisgender, Transgender and Non-Binary Young People.
AB  - Young transgender and non-binary individuals (TNBI) are exposed to situations of
      discrimination and have a greater risk of violence. The purpose of this study is
      to analyze which protective, violence and health and well-being factors have more
      influence on TNBI compared to cisgender people. The sample comprised 856 youth
      between 14 and 25 years old. A survey including questions about sociodemographic
      information and protective, violence and health and well-being factors was
      designed ad hoc for this study. The results show the non-binary group received
      the least support from family and friends, higher risk of suffering
      cyberbullying, and many feel isolated and unhappy. TNBI have suffered more verbal
      attacks both inside and outside their school and physical attacks at school than
      cisgender young. These results are important because they may contribute to the
      promotion of public policies and clinical interventions that favor the
      integration of TNBI in our society.

PMID- 30274142
TI  - Ostreid Herpesvirus-1 Infects Specific Hemocytes in Ark Clam, Scapharca
      broughtonii.
AB  - High levels of ostreid herpesvirus 1 (OsHV-1) were detected in hemocytes of OsHV
      1 infected mollusks. Mollusk hemocytes are comprised of different cell types with
      morphological and functional heterogeneity. Granular cells are considered the
      main immunocompetent hemocytes. This study aimed to ascertain if OsHV-1 infects
      specific types of hemocytes in ark clams. Types of hemocytes were first
      characterized through microexamination and flow cytometry. In addition to a large
      group of red cells, there were three types of recognizable granular cells in ark
      clams. Type II granular cells were mostly found with OsHV-1 infection by
      transmission electron microscope (TEM) examination, and represented the hemocyte
      type that was susceptible to OsHV-1 infection. The subcellular location of OsHV-1
      particles in apoptotic type II granular cells was further analyzed. Some OsHV-1
      particles were free inside the apoptotic cells, which may contribute to OsHV-1
      transmission among cells in the host, some particles were also found enclosed
      inside apoptotic bodies. Apoptosis is an important part of the host defense
      system, but might also be hijacked by OsHV-1 as a strategy to escape host immune
      attack. Following this investigation, a primary culture of type II granular cells
      with OsHV-1 infection would facilitate the research on the interaction between
      OsHV-1 and mollusk hosts.

PMID- 30274143
TI  - Physical Principles of a Piezo Accelerometer Sensitive to a Nearly Constant
      Signal.
AB  - The paper considers the construction of a piezoelectric accelerometer capable of
      measuring constant linear acceleration. A number of designs are proposed that
      make it possible to achieve high sensitivity with small dimensions and a wide
      frequency band (from 10-5 Hz). The finite element model of the proposed design
      was investigated, and its output characteristic and scale factor (36 mV/g) were
      obtained.

PMID- 30274145
TI  - Tungsten-Embedded Graphene: Theoretical Study on a Potential High-Activity
      Catalyst toward CO Oxidation.
AB  - The oxidation mechanism of CO on W-embedded graphene was investigated by M06-2X
      density functional theory. Two models of tungsten atom embedded in single and
      double vacancy (W-SV and W-DV) graphene sheets were considered. It was found that
      over W-SV-graphene and W-DV-graphene, the oxidation of CO prefers to Langmuir
      Hinshelwood (LH) and Eley-Rideal (ER) mechanism, respectively. The two surfaces
      exhibit different catalytic activity during different reaction stages. The
      present results imply that W-embedded graphene is a promising catalyst for CO
      oxidation, which provides a useful reference for the design of a high-efficiency
      catalyst in detecting and removing of toxic gases.

PMID- 30274144
TI  - The Development of a Database for Herbal and Dietary Supplement Induced Liver
      Toxicity.
AB  - The growing use of herbal dietary supplements (HDS) in the United States provides
      compelling evidence for risk of herbal-induced liver injury (HILI). Information
      on HDS products was retrieved from MedlinePlus of the U.S. National Library of
      Medicine and the herbal monograph of the European Medicines Agency. The
      hepatotoxic potential of HDS was ascertained by considering published case
      reports. Other relevant data were collected from governmental documents, public
      databases, web sources, and the literature. We collected information for 296
      unique HDS products. Evidence of hepatotoxicity was reported for 67, that is 1 in
      5, of these HDS products. The database revealed an apparent gender preponderance
      with women representing 61% of HILI cases. Culprit hepatotoxic HDS were mostly
      used for weight control, followed by pain and inflammation, mental stress, and
      mood disorders. Commonly discussed mechanistic events associated with HILI are
      reactive metabolites and oxidative stress, mitochondrial injury, as well as
      inhibition of transporters. HDS-drug interactions, causing both synergistic and
      antagonizing effects of drugs, were also reported for certain HDS. The database
      contains information for nearly 300 commonly used HDS products to provide a
      single-entry point for better comprehension of their impact on public health.

PMID- 30274146
TI  - Insights into the Structural Requirements of 2(S)-Amino-6-Boronohexanoic Acid
      Derivatives as Arginase I Inhibitors: 3D-QSAR, Docking, and Interaction
      Fingerprint Studies.
AB  - Human arginase I (hARGI) is an important enzyme involved in the urea cycle; its
      overexpression has been associated to cardiovascular and cerebrovascular
      diseases. In the last years, several congeneric sets of hARGI inhibitors have
      been reported with possible beneficial roles for the cardiovascular system. At
      the same time, crystallographic data have been reported including hARGI-inhibitor
      complexes, which can be considered for the design of novel inhibitors. In this
      work, the structure-activity relationship (SAR) of Calpha substituted 2(S)-amino
      6-boronohexanoic acid (ABH) derivatives as hARGI inhibitors was studied by using
      a three-dimensional quantitative structure-activity relationships (3D-QSAR)
      method. The predictivity of the obtained 3D-QSAR model was demonstrated by using
      internal and external validation experiments. The best model revealed that the
      differential hARGI inhibitory activities of the ABH derivatives can be described
      by using steric and electrostatic fields; the local effects of these fields in
      the activity are presented. In addition, binding modes of the above-mentioned
      compounds inside the hARGI binding site were obtained by using molecular docking.
      It was found that ABH derivatives adopted the same orientation reported for ABH
      within the hARGI active site, with the substituents at Calpha exposed to the
      solvent with interactions with residues at the entrance of the binding site. The
      hARGI residues involved in chemical interactions with inhibitors were identified
      by using an interaction fingerprints (IFPs) analysis.

PMID- 30274147
TI  - Inhibitory Antibodies against Activin A and TGF-beta Reduce Self-Supported, but
      Not Soluble Factors-Induced Growth of Human Pulmonary Arterial Vascular Smooth
      Muscle Cells in Pulmonary Arterial Hypertension.
AB  - Increased growth and proliferation of distal pulmonary artery vascular smooth
      muscle cells (PAVSMC) is an important pathological component of pulmonary
      arterial hypertension (PAH). Transforming Growth Factor-beta (TGF-beta)
      superfamily plays a critical role in PAH, but relative impacts of self-secreted
      Activin A, Gremlin1, and TGF-beta on PAH PAVSMC growth and proliferation are not
      studied. Here we report that hyper-proliferative human PAH PAVSMC have elevated
      secretion of TGF-beta1 and, to a lesser extent, Activin A, but not Gremlin 1, and
      significantly reduced Ser465/467-Smad2 and Ser423/425-Smad3 phosphorylation
      compared to controls. Media, conditioned by PAH PAVSMC, markedly increased
      Ser465/467-Smad2, Ser423/425-Smad3, and Ser463/465-Smad1/5 phosphorylation, up
      regulated Akt, ERK1/2, and p38 MAPK, and induced significant proliferation of non
      diseased PAVSMC. Inhibitory anti-Activin A antibody reduced PAH PAVSMC growth
      without affecting canonical (Smads) or non-canonical (Akt, ERK1/2, p38 MAPK)
      effectors. Inhibitory anti-TGF-beta antibody significantly reduced P-Smad3, P
      ERK1/2 and proliferation of PAH PAVSMC, while anti-Gremlin 1 had no anti
      proliferative effect. PDGF-BB diminished inhibitory effects of anti-Activin A and
      anti-TGF-beta antibodies. None of the antibodies affected growth and
      proliferation of non-diseased PAVSMC induced by PAH PAVSMC-secreted factors.
      Together, these data demonstrate that human PAH PAVSMC have secretory,
      proliferative phenotype that could be targeted by anti-Activin A and anti-TGF
      beta antibodies; potential cross-talk with PDGF-BB should be considered while
      developing therapeutic interventions.

PMID- 30274148
TI  - The Role of Methionine Sulfoxide Reductases in Oxidative Stress Tolerance and
      Virulence of Staphylococcus aureus and Other Bacteria.
AB  - Methionine sulfoxide reductases (MSRA1 and MSRB) are proteins overproduced in
      Staphylococcus aureus during exposure with cell wall-active antibiotics. Later
      studies identified the presence of two additional MSRA proteins (MSRA2 and MSRA3)
      in S. aureus. These MSR proteins have been characterized in many other bacteria
      as well. This review provides the current knowledge about the conditions and
      regulatory network that mimic the expression of these MSR encoding genes and
      their role in defense from oxidative stress and virulence.

PMID- 30274149
TI  - Role of Hydrogen Sulfide in NRF2- and Sirtuin-Dependent Maintenance of Cellular
      Redox Balance.
AB  - Hydrogen sulfide (H2S) has arisen as a critical gasotransmitter signaling
      molecule modulating cellular biological events related to health and diseases in
      heart, brain, liver, vascular systems and immune response. Three enzymes mediate
      the endogenous production of H2S: cystathione beta-synthase (CBS), cystathione
      gamma-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST). CBS and CSE
      localizations are organ-specific. 3-MST is a mitochondrial and cytosolic enzyme.
      The generation of H2S is firmly regulated by these enzymes under normal
      physiological conditions. Recent studies have highlighted the role of H2S in
      cellular redox homeostasis, as it displays significant antioxidant properties.
      H2S exerts antioxidant effects through several mechanisms, such as quenching
      reactive oxygen species (ROS) and reactive nitrogen species (RNS), by modulating
      cellular levels of glutathione (GSH) and thioredoxin (Trx-1) or increasing
      expression of antioxidant enzymes (AOE), by activating the transcription factor
      nuclear factor (erythroid-derived 2)-like 2 (NRF2). H2S also influences the
      activity of the histone deacetylase protein family of sirtuins, which plays an
      important role in inhibiting oxidative stress in cardiomyocytes and during the
      aging process by modulating AOE gene expression. This review focuses on the role
      of H2S in NRF2 and sirtuin signaling pathways as they are related to cellular
      redox homeostasis.

PMID- 30274150
TI  - The Effects of an Urban Forest Health Intervention Program on Physical Activity,
      Substance Abuse, Psychosomatic Symptoms, and Life Satisfaction among Adolescents.
AB  - Background: At-risk adolescents have been defined as youth who are or might be in
      physical, mental, or emotional danger. An Urban Forest Health Intervention
      Program (UFHIP) was formed at a center for at-risk adolescents in Israel, in
      order to promote physical activity and reduce risky behavior. Objective: To
      evaluate the intervention's effect on physical activity, smoking, alcohol
      consumption, psychosomatic symptoms, and life satisfaction. Methods: From 2015 to
      2016, at-risk youth were nonrandomly selected to participate in the UFHIP.
      Questionnaires were administered to both intervention and control groups before
      and after the intervention. Univariate and multivariable analyses evaluated the
      intervention's effect. Results: The study participants (n = 53) showed 0.81 more
      sessions per week of 60 min of physical activity than did the control group (n =
      23; p = 0.003). Among the intervention group, smoking frequency reduced from a
      mean of 2.60 (SD = 1.30) to 1.72 (SD = 1.08), whereas that in the control group
      increased from 3.17 (1.03) to 3.39 (1.03). In both groups, there was a reduction
      in alcohol consumption, with a greater change among intervention participants: 
      1.08 (SD = 1.30), compared with -0.09 (SD = 1.79) in the control group.
      Conclusions: Findings indicate that the environmental intervention was
      efficacious in increasing physical activity and reducing risky behaviors among
      youth. The effectiveness of this intervention among larger samples is warranted
      in future prospective studies.

PMID- 30274151
TI  - Effect of Colloidal Silica on the Hydration Behavior of Calcium Aluminate Cement.
AB  - The effect of colloidal silica (CS) on the hydrate phases and microstructure
      evolution of calcium aluminate cement (CAC) was investigated. Samples hydrated
      with CS were obtained and characterized by X-ray diffraction (XRD), Field
      Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared
      spectroscopy (FT-IR), hydration heat measurement and Nuclear Magnetic Resonance
      (NMR). The results revealed that SiO2 nanoparticles may affect the hydrates
      crystallization process. There was a compact structure in the CAC paste with CS,
      while petal-shaped hydrates with a porous structure were formed in the pure CAC
      paste. The maximum value of electrical conductivity for CAC paste with CS
      suggested that the early stage of hydration for CAC was accelerated. However, the
      hydration heat curves revealed that the late stage of the CAC hydration process
      was inhibited, and the hydration degree was reduced, this result was in
      accordance with Thermogravimetry-Differential scanning calorimetry(TG-DSC)
      curves. The fitting results of hydration heat curves further showed that the
      hydration degree at NG (nucleation and crystal growth) process stage was
      promoted, while it was limited at the phase boundaries stage, and the diffusion
      stage in the hydration reaction was brought forward due to the addition of CS.
      According to these results and analyses, the differences in the hydration process
      for CAC with and without CS can be attributed to the distribution and nucleation
      effect of SiO2 nanoparticles.

PMID- 30274154
TI  - Microstructure, Mechanical Properties and Tribological Properties of
      NiAlComposites Reinforced by CrMnFeCoNiHigh-Entropy Alloy.
AB  - NiAl-based composites reinforced by CrMnFeCoNi high-entropy alloy (HEA) particles
      were fabricated by mechanical alloying (MA) and spark plasma sintering (SPS). The
      microstructure, mechanical, and tribological properties of the NiAl-HEA
      composites were investigated. Microstructural analyses show that after SPS, the
      HEA phase homogenously distributed in the NiAl matrix. Non-uniform diffusion of
      various elements occurred during the high temperature sintering process.
      Transmission electron microscope (TEM) observation of the composites revealed
      that many nano particle of Al2O3 generated at the grain boundary. The yield
      strength significantly increased after adding HEA particles. The compressive
      strength of the composites increased with the contents of HEA increasing, which
      should be attributed to the second phase hardening effect of HEA particles and
      fine grain strengthening effect. The composite of 10 wt.% HEA exhibited
      significant room temperature compressive properties, with the ultimate
      compressive strength of 2692 MPa and the compressive strain of 34.2%,
      respectively. The results of the wear tests show that the addition of HEA will
      reduce the wear resistance of composites to some extent and slightly increase the
      coefficients of friction (COFs) of the composites.

PMID- 30274152
TI  - Rare Stochastic Expression of O6-Methylguanine- DNA Methyltransferase (MGMT) in
      MGMT-Negative Melanoma Cells Determines Immediate Emergence of Drug-Resistant
      Populations upon Treatment with Temozolomide In Vitro and In Vivo.
AB  - The chemotherapeutic agent temozolomide (TMZ) kills tumor cells preferentially
      via alkylation of the O6-position of guanine. However, cells that express the DNA
      repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), or harbor deficient
      DNA mismatch repair (MMR) function, are profoundly resistant to this drug. TMZ is
      in clinical use for melanoma, but objective response rates are low, even when TMZ
      is combined with O6-benzylguanine (O6BG), a potent MGMT inhibitor. We used in
      vitro and in vivo models of melanoma to characterize the early events leading to
      cellular TMZ resistance. Melanoma cell lines were exposed to a single treatment
      with TMZ, at physiologically relevant concentrations, in the absence or presence
      of O6BG. Surviving clones and mass cultures were analyzed by Western blot, colony
      formation assays, and DNA methylation studies. Mice with melanoma xenografts
      received TMZ treatment, and tumor tissue was analyzed by immunohistochemistry. We
      found that MGMT-negative melanoma cell cultures, before any drug treatment,
      already harbored a small fraction of MGMT-positive cells, which survived TMZ
      treatment and promptly became the dominant cell type within the surviving
      population. The MGMT-negative status in individual cells was not stable, as
      clonal selection of MGMT-negative cells again resulted in a mixed population
      harboring MGMT-positive, TMZ-resistant cells. Blocking the survival advantage of
      MGMT via the addition of O6BG still resulted in surviving clones, although at
      much lower frequency and independent of MGMT, and the resistance mechanism of
      these clones was based on a common lack of expression of MSH6, a key MMR enzyme.
      TMZ treatment of mice implanted with MGMT-negative melanoma cells resulted in
      effective tumor growth delay, but eventually tumor growth resumed, with tumor
      tissue having become MGMT positive. Altogether, these data reveal stochastic
      expression of MGMT as a pre-existing, key determinant of TMZ resistance in
      melanoma cell lines. Although MGMT activity can effectively be eliminated by
      pharmacologic intervention with O6BG, additional layers of TMZ resistance,
      although considerably rarer, are present as well and minimize the cytotoxic
      impact of TMZ/O6BG combination treatment. Our results provide rational
      explanations regarding clinical observations, where the TMZ/O6BG regimen has
      yielded mostly disappointing outcomes in melanoma patients.

PMID- 30274153
TI  - DKB114, A Mixture of Chrysanthemum Indicum Linne Flower and Cinnamomum Cassia
      (L.) J. Presl Bark Extracts, Improves Hyperuricemia through Inhibition of
      Xanthine Oxidase Activity and Increasing Urine Excretion.
AB  - Chrysanthemum indicum Linne flower (CF) and Cinnamomum cassia (L.) J. Presl bark
      (CB) extracts have been used as the main ingredients in several prescriptions to
      treat the hyperuricemia and gout in traditional medicine. In the present study,
      we investigated the antihyperuricemic effects of DKB114, a CF, and CB mixture,
      and the underlying mechanisms in vitro and in vivo. DKB114 markedly reduced serum
      uric acid levels in normal rats and rats with PO-induced hyperuricemia, while
      increasing renal uric acid excretion. Furthermore, it inhibited the activity of
      xanthine oxidase (XOD) in vitro and in the liver in addition to reducing hepatic
      uric acid production. DKB114 decreased cellular uric acid uptake in oocytes and
      HEK293 cells expressing human urate transporter (hURAT)1 and decreased the
      protein expression levels of urate transporters, URAT1, and glucose transporter,
      GLUT9, associated with the reabsorption of uric acid in the kidney. DKB114 exerts
      antihyperuricemic effects and uricosuric effects, which are accompanied,
      partially, by a reduction in the production of uric acid and promotion of uric
      acid excretion via the inhibition of XOD activity and reabsorption of uric acid.
      Therefore, it may have potential as a treatment for hyperuricemia and gout.

PMID- 30274155
TI  - Molecular Application of Aptamers in the Diagnosis and Treatment of Cancer and
      Communicable Diseases.
AB  - Cancer and infectious diseases such as Ebola, HIV, tuberculosis, Zika, hepatitis,
      measles and human schistosomiasis are serious global health hazards. The
      increasing annual morbidities and mortalities of these diseases have been blamed
      on drug resistance and the inefficacy of available diagnostic tools, particularly
      those which are immunologically-based. Antibody-based tools rely solely on
      antibody production for diagnosis and for this reason they are the major cause of
      diagnostic delays. Unfortunately, the control of these diseases depends on early
      detection and administration of effective treatment therefore any diagnostic
      delay is a huge challenge to curbing these diseases. Hence, there is a need for
      alternative diagnostic tools, discovery and development of novel therapeutic
      agents. Studies have demonstrated that aptamers could potentially offer one of
      the best solutions to these problems. Aptamers are short sequences of either DNA
      or RNA molecules, which are identified in vitro through a SELEX process. They are
      sensitive and bind specifically to target molecules. Their promising features
      suggest they may serve as better diagnostic agents and can be used as drug
      carriers for therapeutic purposes. In this article, we review the applications of
      aptamers in the theranostics of cancer and some infectious diseases.

PMID- 30274156
TI  - Novel Biocomposite Engineering and Bio-Applications.

PMID- 30274157
TI  - Implementing Morpholino-Based Nucleic Acid Sensing on a Portable Surface Plasmon
      Resonance Instrument for Future Application in Environmental Monitoring.
AB  - A portable surface plasmon resonance (SPR) instrument was tested for the first
      time for the detection of oligonucleotide sequences derived from the 16S rRNA
      gene of Oleispira antarctica RB-8, a bioindicator species of marine oil
      contamination, using morpholino-functionalized sensor surfaces. We evaluated the
      stability and specificity of morpholino coated sensor surfaces and tested two
      signal amplification regimes: (1) sequential injection of sample followed by
      magnetic bead amplifier and (2) a single injection of magnetic bead captured
      oligo. We found that the sensor surfaces could be regenerated for at least 85
      consecutive sample injections without significant loss of signal intensity.
      Regarding specificity, the assay clearly differentiated analytes with only one or
      two mismatches. Signal intensities of mismatch oligos were lower than the exact
      match target at identical concentrations down to 200 nM, in standard phosphate
      buffered saline with 0.1 % Tween-20 added. Signal amplification was achieved with
      both strategies; however, significantly higher response was observed with the
      sequential approach (up to 16-fold), where first the binding of biotin-probe
      labeled target oligo took place on the sensor surface, followed by the binding of
      the streptavidin magnetic beads onto the immobilized targets. Our experiments so
      far indicate that a simple coating procedure in combination with a relatively
      cost-efficient magnetic-bead-based signal amplification will provide robust SPR
      based nucleic acid sensing down to 0.5 nM of a 45-nucleotide long oligo target
      (7.2 ng/mL).

PMID- 30274158
TI  - Characterization of Distributed Microfabricated Strain Gauges on Stretchable
      Sensor Networks for Structural Applications.
AB  - Smart structures mimic biological systems by using thousands of sensors serving
      as a nervous system analog. One approach to give structures this sensing ability
      is to develop a multifunctional sensor network. Previous work has demonstrated
      stretchable sensor networks consisting of temperature sensors and impact
      detectors for monitoring external environments and interacting with other
      objects. The objective of this work is to develop distributed, robust and
      reliable strain gauges for obtaining the strain distribution of a designated
      region on the target structure. Here, we report a stretchable network that has 27
      rosette strain gauges, 6 resistive temperature devices and 8 piezoelectric
      transducers symmetrically distributed over an area of 150 * 150 mm to map and
      quantify multiple physical stimuli with a spatial resolution of 2.5 * 2.5 mm. We
      performed computational modeling of the network stretching process to improve
      measurement accuracy and conducted experimental characterizations of the
      microfabricated strain gauges to verify their gauge factor and temperature
      coefficient. Collectively, the results represent a robust and reliable sensing
      system that is able to generate a distributed strain profile of a common
      structure. The reported strain gauge network may find a wide range of
      applications in morphing wings, smart buildings, autonomous cars and intelligent
      robots.

PMID- 30274159
TI  - Antimicrobial Resistance in Class 1 Integron-Positive Shiga Toxin-Producing
      Escherichia coli Isolated from Cattle, Pigs, Food and Farm Environment.
AB  - The aim of this study was to investigate the presence of class 1 integrons in a
      collection of Shiga toxin-producing Escherichia coli (STEC) from different
      origins and to characterize pheno- and genotypically the antimicrobial resistance
      associated to them. A collection of 649 isolates were screened for the class 1
      integrase gene (intI1) by Polymerase chain reaction The variable region of class
      1 integrons was amplified and sequenced. Positive strains were evaluated for the
      presence of antimicrobial resistance genes with microarray and for antimicrobial
      susceptibility by the disk diffusion method. Seven out of 649 STEC strains some
      to serogroups, O26, O103 and O130 isolated from cattle, chicken burger, farm
      environment and pigs were identified as positive for intl1. Different
      arrangements of gene cassettes were detected in the variable region of class 1
      integron: dfrA16, aadA23 and dfrA1-aadA1. In almost all strains, phenotypic
      resistance to streptomycin, tetracycline, trimethoprim/sulfamethoxazole, and
      sulfisoxazole was observed. Microarray analyses showed that most of the isolates
      carried four or more antimicrobial resistance markers and STEC strains were
      categorized as Multridrug-resistant. Although antimicrobials are not usually used
      in the treatment of STEC infections, the presence of Multridrug-resistant in
      isolates collected from farm and food represents a risk for animal and human
      health.

PMID- 30274160
TI  - Physiological Effects of Touching the Wood of Hinoki Cypress (Chamaecyparis
      obtusa) with the Soles of the Feet.
AB  - We clarified the physiological effects of tactile stimulation of the soles of the
      feet with the wood of the Hinoki cypress (Chamaecyparis obtusa) based on
      measurements of prefrontal cortex and autonomic nervous activities. Nineteen
      female university-attending students (age: 21.2 +/- 0.3 years) were included. Oxy
      hemoglobin (oxy-Hb) concentrations in the prefrontal cortex were determined by
      using near-infrared time-resolved spectroscopy. The high frequency (HF)
      indicating parasympathetic nervous activity and the ratio of low frequency
      (LF)/HF indicating sympathetic nervous activity were measured using heart rate
      variability. To evaluate the psychological effects caused by contact with the
      materials, the modified semantic differential method was used. The soles of the
      participants' feet were touched to a 600 * 600-mm plate made of Hinoki, which was
      finished in non-coating and brushing for 90 s. A marble plate served as the
      control. Next, subjective evaluation tests were administered to the participants.
      Compared with touching marble, touching Hinoki significantly (1) decreased the
      oxy-Hb concentrations in the left and right prefrontal cortices, which indicates
      decreased prefrontal cortex activity, (2) increased ln(HF), which indicates
      increased parasympathetic nervous activity, (3) decreased ln(LF/HF) ratio, which
      indicates decreased sympathetic nervous activity. Additionally, (4) according to
      subjective evaluations, the participants perceived themselves as being more
      "comfortable," "relaxed," "natural," "warm," "uneven," "dry," and "soft" after
      touching Hinoki. Thus, our cumulative findings indicate that touching Hinoki with
      the soles of the feet induces physiological relaxation.

PMID- 30274161
TI  - An Adaptive Zero Velocity Detection Algorithm Based on Multi-Sensor Fusion for a
      Pedestrian Navigation System.
AB  - The zero velocity update (ZUPT) algorithm is an effective way to suppress the
      error growth for a foot-mounted pedestrian navigation system. To make ZUPT work
      properly, it is necessary to detect zero velocity intervals correctly. Existing
      zero velocity detection methods cannot provide good performance at high gait
      speeds or stair climbing. An adaptive zero velocity detection approach based on
      multi-sensor fusion is proposed in this paper. The measurements of an
      accelerometer, gyroscope and pressure sensor were employed to construct a zero
      velocity detector. Then, the adaptive threshold was proposed to improve the
      accuracy of the detector under various motion modes. In addition, to eliminate
      the height drift, a stairs recognition method was developed to distinguish
      staircase movement from level walking. Detection performance was examined with
      experimental data collected at varying motion modes in real scenarios. The
      experimental results indicate that the proposed method can correctly detect zero
      velocity intervals under various motion modes.

PMID- 30274162
TI  - Aqueous Synthesis, Degradation, and Encapsulation of Copper Nanowires for
      Transparent Electrodes.
AB  - Copper nanowires (CuNWs) have increasingly become subjected to academic and
      industrial research, which is attributed to their good performance as a
      transparent electrode (TE) material that competes with the one of indium tin
      oxide (ITO). Recently, an environmentally friendly and aqueous synthesis of CuNWs
      was demonstrated, without the use of hydrazine that is known for its unfavorable
      properties. In this work, we extend the current knowledge for the aqueous
      synthesis of CuNWs by studying their up-scaling potential. This potential is an
      important aspect for the commercialization and further development of CuNW-based
      devices. Due to the scalability and homogeneity of the deposition process, spray
      coating was selected to produce films with a low sheet resistance of 7.6
      Omega/sq. and an optical transmittance of 77%, at a wavelength of 550 nm.
      Further, we present a comprehensive investigation of the degradation of CuNWs
      when subjected to different environmental stresses such as the exposure to
      ambient air, elevated temperatures, high electrical currents, moisture or
      ultraviolet (UV) light. For the oxidation process, a model is derived to describe
      the dependence of the breakdown time with the temperature and the initial
      resistance. Finally, polymer coatings made of polydimethylsiloxane (PDMS) and
      polymethylmethacrylate (PMMA), as well as oxide coatings composed of electron
      beam evaporated silicon dioxide (SiO2) and aluminum oxide (Al2O3) are tested to
      hinder the oxidation of the CuNW films under current flow.

PMID- 30274165
TI  - Polarimetric-Phase-Enhanced Intensity Interrogation Scheme for Surface Wave
      Optical Sensors with Low Optical Loss.
AB  - A polarimetric-phase-enhanced intensity interrogation scheme leveraging the
      polarization-dependent sharp phase change induced by the surface wave excitation
      at a low-optical-loss sensor's surface is proposed and experimentally
      demonstrated. Based on a simple setup with no moving parts during interrogation,
      a polarimetric-phase-enhanced intensity can be obtained by subtracting the
      reflected intensities of two beam polarization states. Our results show a ~4-fold
      sensitivity increase compared to traditional intensity detection schemes for
      similar sensors. As novel surface wave optical sensors are designed and
      engineered with optimized phase responses, this scheme offers a low-complexity
      solution for such devices instead of traditional phase interrogation schemes.

PMID- 30274164
TI  - Acute Kidney Injury Definition and Diagnosis: A Narrative Review.
AB  - Acute kidney injury (AKI) is a complex syndrome characterized by a decrease in
      renal function and associated with numerous etiologies and pathophysiological
      mechanisms. It is a common diagnosis in hospitalized patients, with increasing
      incidence in recent decades, and associated with poorer short- and long-term
      outcomes and increased health care costs. Considering its impact on patient
      prognosis, research has focused on methods to assess patients at risk of
      developing AKI and diagnose subclinical AKI, as well as prevention and treatment
      strategies, for which an understanding of the epidemiology of AKI is crucial. In
      this review, we discuss the evolving definition and classification of AKI, and
      novel diagnostic methods.

PMID- 30274166
TI  - Enhancing Multiple Jets in Electrospinning: The Role of Auxiliary Electrode.
AB  - An auxiliary electrode introduced in traditional spinneret electrospinning is an
      effective and powerful technique to improve the production rate of nanofibers. In
      this work, the effects of the arrangement of auxiliary electrode, applied
      voltage, injection speed, and the distance between the electrode tip and the
      spinneret tip (ESD) on the jet number and the morphology of polyvinyl alcohol
      (PVA) nanofibers were investigated systematically. The results showed that the
      number of jets firstly increased and then decreased with the increase of applied
      voltage and ESD, respectively, while increasing with the injection speed in both
      the auxiliary electrode in the vertical position and parallel position. The
      average nanofiber diameter decreased with increasing of applied voltage and
      injection speed, but decreasing in ESD in these two positions. The numerical
      simulation results revealed that the auxiliary electrode primarily influenced the
      electric field intensity in the spinning area. This work provides a deep
      understanding of multiple jets in electrospinning.

PMID- 30274163
TI  - Adverse Childhood Experiences in Children with Intellectual Disabilities: An
      Exploratory Case-File Study in Dutch Residential Care.
AB  - Adverse Childhood Experiences (ACEs) are negative childhood events occurring in a
      child's family or social environment, that may cause harm or distress. Children
      with intellectual disabilities (ID) and their families are underrepresented in
      international ACEs research, while current insights can also contribute to the
      improvement of their health and well-being. Deficiencies in intellectual and
      adaptive functioning and living circumstances can increase their vulnerability to
      adversities. In the present exploratory study 69 case-files of children referred
      to a Dutch national center for residential youth care for children with ID were
      analyzed to assess the prevalence and associations of ACEs. It was found that
      almost half (49.3%) of the children experienced 2 ACEs from the original ACEs
      framework or more (M (mean) = 2.1; SD (standard deviation) = 1.8) and that the
      number of ACEs in children was related to the presence of ACEs in parents. Both
      child and parental ACEs were also related to attachment- and trauma- and stressor
      related disorders. Finally, living circumstances and multiple ACEs from the
      expanded ACEs framework, especially related to parental characteristics, were
      found to be related to ACEs in children with ID. This implicates the importance
      of a transgenerational approach when further investigating the impact of ACEs on
      mental and physical health in children with ID (intellectual disabilities).

PMID- 30274167
TI  - Regulation of Macrophage Activation and Polarization by HCC-Derived Exosomal
      lncRNA TUC339.
AB  - Exosomes released by cells can serve as vehicles for delivery of biological
      materials and signals. Long non-coding RNAs (lncRNAs) are non-coding RNAs longer
      than 200 nt, which roles are increasingly appreciated in various biological
      content. Tumor-derived exosomal lncRNAs have been implicated as signaling
      mediators to orchestrate cell function among neighbor tumor cells. However, the
      role of tumor-derived lncRNAs in cross-talk with environmental macrophages has
      yet to be explored. In this paper, we demonstrated that hepatocellular carcinoma
      (HCC) cells-derived exosomes contain elevated levels of lncRNA TUC339 and that
      HCC-derived exosomes could be taken up by THP-1 cells. In seeking to dissect the
      biological function of tumor secreting TUC339 in macrophages, we applied loss-of
      function and gain-of-function strategies. We observed increased pro-inflammatory
      cytokine production, increased co-stimulatory molecule expression, and enhanced
      phagocytosis upon suppression of TUC339 by siRNA in THP-1 cells, and the opposite
      effect upon over-expression of this lncRNA, which indicates that TUC339 was
      involved in the regulation of macrophage activation. Moreover, we detected an
      elevated level of TUC339 in M(IL-4) macrophages as compared to M(IFN-gamma + LPS)
      macrophages and a down-regulation of TUC339 expression during M(IL-4)-to-M(IFN
      gamma + LPS) repolarization and vice versa. Furthermore, suppression of TUC339 in
      macrophages diminished the expression of M(IL-4) markers upon IL-4 treatment
      while overexpression of TUC339 in macrophages enhanced M(IL-4) markers upon IFN
      gamma + LPS treatment, which suggests a critical function of TUC339 in the
      regulation of macrophage M1/M2 polarization. Lastly, using microarray analysis,
      we identified cytokine-cytokine receptor interaction, CXCR chemokine receptor
      binding, Toll-like receptor signaling, FcgammaR-mediated phagocytosis, regulation
      of the actin cytoskeleton, and cell proliferation are related with TUC339
      function in macrophages. Our results provide evidence for a novel regulatory
      function of tumor-derived exosomal lncRNA TUC339 in environmental macrophages and
      shed light on the complicated interactions between tumor and immune cells through
      exosomal lncRNAs.

PMID- 30274168
TI  - Ectopic Overexpression of Porcine Myh1 Increased in Slow Muscle Fibers and
      Enhanced Endurance Exercise in Transgenic Mice.
AB  - Myosin heavy chain (MyHC) isoforms consist of Myh7, Myh2, Myh1, and Myh4, which
      are expressed in skeletal muscle tissues during postnatal development. These
      genes influence the contraction-relaxation activity in skeletal muscles and are
      involved in determining muscle composition such as the proportion of fast-to-slow
      and/or slow-to-fast fiber types. Among them, Myh1 is associated with skeletal
      muscle contraction and is involved in both slow-to-fast and fast-to-slow
      transition. However, the muscle transition mechanism is not well understood. For
      this study, we first produced porcine Myh1 transgenic (TG) mice to study whether
      the ectopic expressed porcine Myh1 gene had any effects on muscle composition,
      especially on slow-type muscle components. Our results showed that the factors
      associated with slow muscles, such as Myh7, Myoglobin, Troponin (slow-type
      units), and cytochrome C, were highly expressed in the quadriceps muscles of Myh1
      transgenic mice. Furthermore, the ectopic porcine MYH1 protein was located only
      in the slow-type muscle fibers of the quadriceps muscles in Myh1 transgenic mice.
      In physical endurance tests, Myh1 transgenic mice ran longer and further on a
      treadmill than wild-type (WT) mice. These data fully supported our hypothesis
      that Myh1 is associated with slow muscle composition, with overexpression of Myh1
      in muscle tissues possibly being a new key in modulating muscle fiber types. Our
      study provides a better understanding of muscle composition metabolism, physical
      mobility, and genetic factors in muscle fatigue.

PMID- 30274169
TI  - Reactivation of Latent Epstein-Barr Virus: A Comparison after Exposure to Gamma,
      Proton, Carbon, and Iron Radiation.
AB  - Among the many stressors astronauts are exposed to during spaceflight, cosmic
      radiation may lead to various serious health effects. Specifically, space
      radiation may contribute to decreased immunity, which has been documented in
      astronauts during short- and long-duration missions, as evidenced by several
      changes in cellular immunity and plasma cytokine levels. Reactivation of latent
      herpes viruses, either directly from radiation of latently infected cells and/or
      from perturbation of the immune system, may result in disease in astronauts.
      Epstein-Barr virus (EBV) is one of the eight human herpes viruses known to infect
      more than 90% of human adults and persists for the life of the host without
      normally causing adverse effects. Reactivation of several latent viruses in
      astronauts is well documented, although the mechanism of reactivation is not well
      understood. We studied the effect of four different types of radiation, (1) 137Cs
      gamma rays, (2) 150-MeV protons, (3) 600 MeV/n carbon ions, and (4) 600 MeV/n
      iron ions on the activation of lytic gene transcription and of reactivation of
      EBV in a latently infected cell line (Akata) at doses of 0.1, 0.5, 1.0, and 2.0
      Gy. The data showed that for all doses used in this study, lytic gene
      transcription was induced and median viral loads were significantly higher for
      all types of radiation than in corresponding control samples, with the increases
      detected as early as four days post-exposure and generally tapering off at later
      time points. The viability and size of EBV-infected Akata cells were highly
      variable and exhibited approximately the same trend in time for all radiation
      types at 0.1, 0.5, 1.0, and 2.0 Gy. This work shows that reactivation of viruses
      can occur due to the effect of different types of radiation on latently infected
      cells in the absence of changes or cytokines produced in the immune system. In
      general, gamma rays are more effective than protons, carbon ions, and iron ions
      in inducing latent virus reactivation, though these high-energy particles did
      induce more sustained and later reactivation of EBV lytic gene transcription.
      These findings also challenge the common relative biological effectiveness
      concept that is often used in radiobiology for other end points.

PMID- 30274170
TI  - Mechanical Property Tests and Strength Formulas of Basalt Fiber Reinforced
      Recycled Aggregate Concrete.
AB  - In order to investigate the influence of basalt fibers (BFs) on the mechanical
      performance of recycled aggregate concrete (RAC), some groups of RAC specimens
      were first tested involving different types of fibers such as carbon fibers,
      steel fibers, polypropylene fibers and hybrid fibers. The main four indices for
      the investigation consisted of cube compressive strengths, axial compressive
      strengths, splitting tensile strengths and Young's modulus. The effects of fiber
      volume fractions on the RAC slumps were also discussed. Meanwhile, the mechanical
      properties and failure modes of the BF-reinforced RAC were compared with those of
      other fiber-reinforced RAC and common concrete (CC). Subsequently the optimal
      volume fractions of BFs were explored for different mechanical properties within
      the volume fraction range of 0-0.2%. The back propagation neural networks were
      further applied to predict and validate the optimal BF fractions. Lastly, the
      general strength formulas, as well as the elastic modulus formula, for BF
      reinforced RAC were deducted based on the specimen test results. It is found that
      the addition of fibers may improve the failure modes of RAC and different fibers
      present positive or negative effects on the mechanical properties. The optimal
      volume fractions of BF with respect to the four mechanical indices are 0.1%,
      0.15%, 0.1% and 0.2% respectively. The proposed strength and elastic modulus
      formulas of BF-reinforced RAC provide satisfactory predictions with the test
      results and thus can be used as a reference in practice.

PMID- 30274171
TI  - The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve
      Fibers in the Wall of Porcine Uterus.
AB  - Bisphenol A (BPA), a substance commonly used in the manufacture of plastics,
      shows multidirectional negative effects on humans and animals. Due to
      similarities to estrogens, BPA initially leads to disorders in the reproductive
      system. On the other hand, it is known that neuregulin 1 (NRG-1) is an active
      substance which enhances the survivability of cells, inhibits apoptosis, and
      protects tissues against damaging factors. Because the influence of BPA on the
      nervous system has also been described, the aim of the present study was to
      investigate for the first time the influence of various doses of BPA on
      neuregulin 1-like immunoreactive (NRG-1-LI) nerves located in the porcine uterus
      using the routine single- and double-immunofluorescence technique. The obtained
      results have shown that BPA increases the number and affects the neurochemical
      characterization of NRG-1-LI in the uterus, and changes are visible even under
      the impact of small doses of this toxin. The character of observed changes
      depended on the dose of BPA and the part of the uterus studied. These
      observations suggest that NRG-1 in nerves supplying the uterus may play roles in
      adaptive and protective mechanisms under the impact of BPA.

PMID- 30274173
TI  - Comment on Ultrasound Guidance for Botulinum Neurotoxin Chemodenervation
      Procedures. Toxins 2017, 10, 18-Quintessential Use of Ultrasound Guidance for
      Botulinum Toxin Injections-Muscle Innervation Zone Targeting Revisited.
AB  - Recently, the importance of targeting structures during botulinum neurotoxin
      applications has been discussed in a variety of disorders, including spasticity
      and dystonia. In this respect, the advantages of ultrasound imaging to
      traditional techniques have been emphasized. We would like underscore the
      importance of ultrasound guidance, with targeting innervation zone(s) of the over
      active muscles to achieve effective clinical outcomes. Additionally, we also
      clarify the difference between the terms-innervation zone (motor end plate) and
      motor point-which have been used by the authors as if they were the same.
      Further, we disagree with the authors about the intramuscular botulinum
      neurotoxin application techniques i.e., in-plane vs. out-of-plane whereby the
      former is, for sure, superior.

PMID- 30274172
TI  - Alterations in Gastric Mucosal Expression of Calcitonin Gene-Related Peptides,
      Vanilloid Receptors, and Heme Oxygenase-1 Mediate Gastroprotective Action of
      Carbon Monoxide against Ethanol-Induced Gastric Mucosal Lesions.
AB  - Carbon monoxide (CO) has been reported to contribute to the maintenance of
      gastric mucosal integrity, gastroprotection, and ulcer healing. However,
      involvement of transient receptor potential vanilloid receptor type 1 (TRPV1)
      located on afferent sensory fibers endings and sensory neuropeptide calcitonin
      gene-related peptide (CGRP) in CO-mediated gastroprotection against ethanol
      induced gastric damage has not been explored. Male Wistar rats with and without
      denervation of afferent sensory neurons induced by capsaicin (total dose 125
      mg/kg within 3 days) were pretreated with vehicle, CO donor
      tricarbonyldichlororuthenium (II) dimer (CORM-2, 5 mg/kg i.g.), administered
      alone or with CGRP-alpha (10 MUg/kg i.p.) or TRPV1 antagonist capsazepine (5
      mg/kg i.g.), followed 30 min later by intragastric (i.g.) administration of 75%
      ethanol. The area of gastric damage and gastric blood flow (GBF) were assessed
      planimetrically and by laser flowmetry, respectively. Microscopic evaluation of
      ethanol-induced gastric lesions was performed after haematoxylin/eosin (H&E) or
      alcian blue/periodic acid-Schiff/alcian blue (AB/PAS) staining. Gastric mucosal
      mRNA fold change for heme oxygenase (HMOX)-1, HMOX-2, CGRP-alpha, CGRP-beta,
      inducible nitric oxide synthase (iNOS), endothelial (e)NOS, neuronal (n)NOS,
      cyclooxygenase (COX)-1, COX-2, and protein expression for HMOX-1 and TRPV1 was
      determined by real-time PCR or Western blot, respectively. Pretreatment with CORM
      2 combined or not with CGRP reduced ethanol-induced gastric lesions and elevated
      GBF. Capsaicin-denervation or co-treatment with capsazepine or CGRP and CORM-2 in
      capsaicin-denervated animals failed to affect these beneficial effects of CO
      donor. In rats with intact sensory nerves, CORM-2 increased gastric mRNA level
      for HMOX-1 and CGRP-alpha. In capsaicin-denervated rats, CORM-2 increased eNOS
      mRNA fold change and TRPV1 protein expression while capsaicin denervation itself
      decreased HMOX-1 protein expression and eNOS mRNA level. We conclude that CO
      prevents gastric mucosa from ethanol-induced lesions due to activation of
      TRPV1/CGRP-alpha system and accompanying increase in gastric microcirculation but
      independently on afferent sensory nerve activity despite the stimulation of TRPV1
      protein and CGRP-alpha mRNA expression.

PMID- 30274174
TI  - Influence of Beam Offset on Dissimilar Laser Welding of Molybdenum to Titanium.
AB  - Dissimilar joining of molybdenum (Mo) to titanium (Ti) is of great significance
      to the design and fabrication of high-temperature facilities. However, few
      reports were found about fusion joining of these two metals. The objective of
      this paper is to assess the feasibility of laser beam welding (LBW) of 2 mm-thick
      molybdenum and titanium. The effects of laser beam offset on the laser dissimilar
      joint of pure molybdenum to pure titanium were analyzed in terms of
      microstructure, chemical composition, microhardness, and tensile behavior. The
      results showed that the weld appearance improved with the increase of the offset.
      The fusion zone was strengthened because of the solid solution of these two
      elements. The mechanical properties of samples increased firstly and then
      decreased with the increasing of offset. When the laser beam irradiated on the
      titanium plate and the center of the laser spot was 0.5 mm away from the Mo/Ti
      interface, the joint performed the highest tensile strength, which was about 70%
      that of titanium base metal. LBW was demonstrated to be a promising method to
      join dissimilar Mo/Ti joint.

PMID- 30274175
TI  - Hazardous Drinking among Students over a Decade of University Policy Change:
      Controlled Before-and-After Evaluation.
AB  - Background: Responding to high levels of alcohol-related harm among students, a
      New Zealand university deployed a security and liaison service, strengthened the
      Student Code of Conduct, increased its input on the operation of alcohol outlets
      near campus, and banned alcohol advertising on campus. We estimated the change in
      the prevalence of alcohol consumption patterns among students at the university
      compared with other universities. Methods: We conducted a controlled before-and
      after study with surveys in residential colleges at the target university in 2004
      and 2014, and in random samples of students at the target university and three
      control universities in 2005 and 2013. The primary outcome was the prevalence of
      recent intoxication, while we analysed drinking per se and drinking in selected
      locations to investigate mechanisms of change. Results: The 7-day prevalence of
      intoxication decreased from 45% in 2004 to 33% in 2014 (absolute difference: 12%;
      95% CI: 7% to 17%) among students living in residential colleges, and from 40% in
      2005 to 26% in 2013 (absolute difference: 14%; 95% CI: 8% to 20%) in the wider
      student body of the intervention university. The intervention effect estimate,
      representing the change at the intervention university adjusted for change at
      other universities (aOR = 1.30; 95% CI: 0.89 to 1.90), was consistent with a
      benefit of intervention but was not statistically significant (p = 0.17).
      Conclusion: In this period of alcohol policy reform, drinking to intoxication
      decreased substantially in the targeted student population. Policy reforms and
      coincidental environmental changes may each have contributed to these reductions.

PMID- 30274176
TI  - Fenofibrate Interferes with the Diapedesis of Lung Adenocarcinoma Cells through
      the Interference with Cx43/EGF-Dependent Intercellular Signaling.
AB  - Extravasation of circulating cancer cells is regulated by the
      intercellular/intracellular signaling pathways that locally impair the
      endothelial barrier function. Co-cultures of human umbilical vein endothelial
      cells (HUVECs) with lung adenocarcinoma A549 cells enabled us to identify these
      pathways and to quantify the effect of fenofibrate (FF) on their activity. A549
      cells induced the disruption and local activation of endothelial continuum. These
      events were accompanied by epidermal growth factor (EGF) up-regulation in
      endothelial cells. Impaired A549 diapedesis and HUVEC activation were seen upon
      the chemical inhibition of connexin(Cx)43 functions, EGF/ERK1/2-dependent
      signaling, and RhoA/Rac1 activity. A total of 25 MUM FF exerted corresponding
      effects on Cx43-mediated gap junctional coupling, EGF production, and ERK1/2
      activation in HUVEC/A549 co-cultures. It also directly augmented endothelial
      barrier function via the interference with focal adhesion kinase (FAK)/RhoA/Rac1
      regulated endothelial cell adhesion/contractility/motility and prompted the
      selective transmigration of epithelioid A549 cells. N-acetyl-L-cysteine abrogated
      FF effects on HUVEC activation, suggesting the involvement of PPARalpha
      independent mechanism(s) in its action. Our data identify a novel
      Cx43/EGF/ERK1/2/FAK/RhoA/Rac1-dependent signaling axis, which determines the
      efficiency of lung cancer cell diapedesis. FF interferes with its activity and
      reduces the susceptibility of endothelial cells to A549 stimuli. These findings
      provide the rationale for the implementation of FF in the therapy of malignant
      lung cancers.

PMID- 30274178
TI  - Can Aluminum Tolerant Wheat Cultivar Perform Better under Phosphate Deficient
      Conditions?
AB  - Low availability of inorganic phosphate (Pi), together with aluminum (Al), is a
      major constraint for plant growth and development in acidic soils. To investigate
      whether or not Al-resistant cultivars can perform better under Pi deficiency, we
      chose two wheat cultivars with different Al-responses-Atlas 66, being Al
      tolerant, and Scout 66, which is Al-sensitive-and analyzed their responses to Pi
      deficiency. Results showed that, unexpectedly, the Al-sensitive cultivar Scout 66
      contained comparatively higher amount of soluble phosphate (Pi) and total
      phosphorus (P) both in the roots and in the shoots than Atlas 66 under P
      deficiency. In addition, Scout 66 exhibited higher root biomass, root volume, and
      root tip numbers, compared with Atlas 66. The expression of Pi-responsive marker
      genes, TaIPS1, TaSPX3, and TaSQD2 was strongly induced in both cultivars, but the
      extents of induction were higher in Scout 66 than in Atlas 66 under long-term Pi
      starvation. Taken together, our results suggest that the Al-sensitive cultivar
      Scout 66 performed much better under sole Pi starvation, which sets the following
      experimental stage to uncover the underlying mechanisms of why Scout 66 can
      display better under Pi deficiency. Our study also raises an open question
      whether Al-resistant plants are more sensitive to Pi deficiency.

PMID- 30274177
TI  - Multifunctional Cargo-Free Nanomedicine for Cancer Therapy.
AB  - Nanocarriers encapsulating multiple chemotherapeutics are a promising strategy to
      achieve combinational chemotherapy for cancer therapy; however, they generally
      use exotic new carriers without therapeutic effect, which usually suffer from
      carrier-related toxicity issues, as well as having to pass extensive clinical
      trials to be drug excipients before any clinical applications. Cargo-free
      nanomedicines, which are fabricated by drugs themselves without new excipients
      and possess nanoscale characteristics to realize favorable pharmacokinetics and
      intracellular delivery, have been rapidly developed and drawn much attention to
      cancer treatment. Herein, we discuss recent advances of cargo-free nanomedicines
      for cancer treatment. After a brief introduction to the major types of carrier
      free nanomedicine, some representative applications of these cargo-free
      nanomedicines are discussed, including combination therapy, immunotherapy, as
      well as self-monitoring of drug release. More importantly, this review draws a
      brief conclusion and discusses the future challenges of cargo-free nanomedicines
      from our perspective.

PMID- 30274179
TI  - Lysine Acetylation Regulates Alanyl-tRNA Synthetase Activity in Escherichia coli.
AB  - Protein lysine acetylation is a widely conserved posttranslational modification
      in all three domains of life. Lysine acetylation frequently occurs in aminoacyl
      tRNA synthetases (aaRSs) from many organisms. In this study, we determined the
      impact of the naturally occurring acetylation at lysine-73 (K73) in Escherichia
      coli class II alanyl-tRNA synthetase (AlaRS) on its alanylation activity. We
      prepared an AlaRS K73Ac variant in which Nepsilon-acetyl-l-lysine was
      incorporated at position 73 using an expanded genetic code system in E. coli. The
      AlaRS K73Ac variant showed low activity compared to the AlaRS wild type (WT).
      Nicotinamide treatment or CobB-deletion in an E. coli led to elevated acetylation
      levels of AlaRS K73Ac and strongly reduced alanylation activities. We assumed
      that alanylation by AlaRS is affected by K73 acetylation, and the modification is
      sensitive to CobB deacetylase in vivo. We also showed that E. coli expresses two
      CobB isoforms (CobB-L and CobB-S) in vivo. CobB-S displayed the deacetylase
      activity of the AlaRS K73Ac variant in vitro. Our results imply a potential
      regulatory role for lysine acetylation in controlling the activity of aaRSs and
      protein synthesis.

PMID- 30274180
TI  - Recent Advances in Shiga Toxin-Producing Escherichia coli Research in Latin
      America.
AB  - Pathogenic Escherichia coli are known to be a common cause of diarrheal disease
      and a frequently occurring bacterial infection in children and adults in Latin
      America. Despite the effort to combat diarrheal infections, the south of the
      American continent remains a hot spot for infections and sequelae associated with
      the acquisition of one category of pathogenic E. coli, the Shiga toxin-producing
      E. coli (STEC). This review will focus on an overview of the prevalence of
      different STEC serotypes in human, animals and food products, focusing on recent
      reports from Latin America outlining the recent research progress achieved in
      this region to combat disease and endemicity in affected countries and to improve
      understanding on emerging serotypes and their virulence factors. Furthermore,
      this review will highlight the progress done in vaccine development and treatment
      and will also discuss the effort of the Latin American investigators to respond
      to the thread of STEC infections by establishing a multidisciplinary network of
      experts that are addressing STEC-associated animal, human and environmental
      health issues, while trying to reduce human disease. Regardless of the
      significant scientific contributions to understand and combat STEC infections
      worldwide, many significant challenges still exist and this review has focus in
      the Latin American efforts as an example of what can be accomplished when
      multiple groups have a common goal.

PMID- 30274181
TI  - An Optimized Relay Selection Technique to Improve the Communication Reliability
      in Wireless Sensor Networks.
AB  - Wireless Sensor Networks (WSN) are enabler technologies for the implementation of
      the Internet of Things (IoT) concept. WSNs provide an adequate infrastructure for
      the last-link communication with smart objects. Nevertheless, the wireless
      communication medium being inherently unreliable, there is the need to increase
      its communication reliability. Techniques based on the use of cooperative
      communication concepts are one of the ways to achieve this target. Within
      cooperative communication techniques, nodes selected as relays transmit not only
      their own data, but also cooperate by retransmitting data from other nodes. A
      fundamental step to improve the communication reliability of WSNs is related to
      the use of efficient relay selection techniques. This paper proposes a relay
      selection technique based on multiple criteria to select the smallest number of
      relay nodes and, at the same time, to ensure an adequate operation of the
      network. Additionally, two relay updating schemes are also investigated, defining
      periodic and adaptive updating policies. The simulation results show that both
      proposed schemes, named Periodic Relay Selection and Adaptive Relay Selection,
      significantly improve the communication reliability of the network, when compared
      to other state-of-the-art relay selection schemes.

PMID- 30274182
TI  - Research on a Mixed Gas Recognition and Concentration Detection Algorithm Based
      on a Metal Oxide Semiconductor Olfactory System Sensor Array.
AB  - As a typical machine olfactory system index, the accuracy of hybrid gas
      identification and concentration detection is low. This paper proposes a novel
      hybrid gas identification and concentration detection method. In this method,
      Kernel Principal Component Analysis (KPCA) is employed to extract the nonlinear
      mixed gas characteristics of different components, and then K-nearest neighbour
      algorithm (KNN) classification modelling is utilized to realize the recognition
      of the target gas. In addition, this method adopts a multivariable relevance
      vector machine (MVRVM) to regress the multi-input nonlinear signal to realize the
      detection of the concentration of the hybrid gas. The proposed method is
      validated by using CO and CH4 as the experimental system samples. The
      experimental results illustrate that the accuracy of the proposed method reaches
      98.33%, which is 5.83% and 14.16% higher than that of principal component
      analysis (PCA) and independent component analysis (ICA), respectively. For the
      hybrid gas concentration detection method, the CO and CH4 concentration detection
      average relative errors are reduced to 5.58% and 5.38%, respectively.

PMID- 30274185
TI  - Serum VEGF Level Is Different in Adolescents Smoking Waterpipe versus Cigarettes:
      The Irbid TRY.
AB  - Waterpipe (Wp) use is associated with most devastating diseases and particularly
      popular among adolescents. Vascular endothelium growth factor (VEGF) is essential
      for generating new vessels. The effect of smoking tobacco on VEGF is
      controversial and unknown among adolescents. Therefore, the current study
      compared serum VEGF in adolescents smoking cigarettes (Cg) only (9.3%), Wp only
      (19.6%), and dual (Wp and Cg) (36.4%) versus nonsmokers (34.6%) in adolescents. A
      self-reported questionnaire and enzyme-linked immunosorbent assay (ELISA) were
      used to obtain smoking status and serum VEGF, respectively, in 475 (age: 14.6 +/-
      1.0 years) boys (n = 263) and girls (n = 212) from Irbid, Jordan. The analysis
      showed that smoking status (R2 = 0.021; p = 0.001) and gender (R2 = 0.035; p =
      0.000) can predict VEGF. Furthermore, 2-way-ANCOVA revealed that VEGF was lower
      in the dual cohort versus the Cg (33.4%; p = 0.04) and nonsmoker (29.6%; p =
      0.003) cohorts; VEGF in smokers, was lower (33.6%; p = 0.04) in the Wp versus
      nonsmokers in the boys but not the girls. These results are unique and suggest
      that smoking lowers VEGF, which might adversely affect vascular growth and
      function. This is alarming given that adolescents are still in the development
      stage and smoking, particularly Wp, is popular among them. Therefore,
      interventions targeting smoking among schoolchildren are urgently needed to avoid
      the negative effects of smoking, especially on vascular health.

PMID- 30274184
TI  - Influence of Luting Materials on the Retention of Cemented Implant-Supported
      Crowns: An In Vitro Study.
AB  - The retention force of cemented crowns on implant abutments with various luting
      materials was evaluated. Cobalt-chromium crowns were cemented onto tapered
      titanium abutments (Camlog) with eugenol-free temporary cement (RelyX TempBond
      NE), composite-based temporary cement (Bifix Temp), zinc phosphate cement
      (Harvard Cement), glass-ionomer cements (Meron, Fuji I), and resin-modified glass
      ionomer cements (Fuji II, Fuji Plus, Ketac Cem Plus). Specimen aging via
      hydrostress was performed in artificial saliva at 37  degrees C for 14 days (S1),
      followed by hydrothermal stress with thermocycling (S2). The crowns were removed,
      and the force was recorded (T1). Subsequently, the crowns were recemented, aged,
      and removed, and the force was recorded (T2, T3). The retention forces
      differences were statistically significant according to the storage conditions at
      T1 (p = 0.002) and T3 (p = 0.0002). After aging (S1), Ketac Cem Plus had the
      highest retention force median value difference (T3 versus T1) (-773 N), whereas
      RelyX TempBond NE had the lowest (-146 N). After aging (S2), Meron had the
      highest retention force median value difference (-783 N), whereas RelyX TempBond
      NE had the lowest (-168 N). Recementation decreased the retention force of the
      implant-supported cobalt-chromium crowns cemented and recemented with the same
      luting materials. Luting materials (at T1) and aging conditions significantly
      impacted the retention force.

PMID- 30274183
TI  - Sensitization of Cancer Cells to Radiation and Topoisomerase I Inhibitor
      Camptothecin Using Inhibitors of PARP and Other Signaling Molecules.
AB  - Radiation and certain anticancer drugs damage DNA, resulting in apoptosis
      induction in cancer cells. Currently, the major limitations on the efficacy of
      such therapies are development of resistance and adverse side effects.
      Sensitization is an important strategy for increasing therapeutic efficacy while
      minimizing adverse effects. In this manuscript, we review possible sensitization
      strategies for radiation and anticancer drugs that cause DNA damage, focusing
      especially on modulation of damage repair pathways and the associated reactions.

PMID- 30274186
TI  - Bitumen Foaming Optimisation Process on the Basis of Rheological Properties.
AB  - This article discusses the results of bitumen foam properties optimisation with
      respect to three factors: air pressure, bitumen temperature and amount of water.
      The test materials were unmodified bitumen 50/70 and bitumen 50/70 modified with
      2.5% synthetic wax. The experiment was designed according to the 3(3-1)
      fractional factorial design. The distribution of parameters of bitumen foam were
      measured with the authors' original apparatus using a laser beam. This
      measurement method increased the accuracy of maximum expansion ratio (ER) and
      half-life (HL) estimation. Based on HL and ER results, it was found that the
      foaming process increased bitumen stiffness due to the dynamic ageing of the
      bitumen. The experimental design allows more effective control over the
      properties of foamed bitumen with respect to its intended use. The presence of
      synthetic wax extended the half-life of the bitumen foam.

PMID- 30274187
TI  - GesID: 3D Gesture Authentication Based on Depth Camera and One-Class
      Classification.
AB  - Biometric authentication is popular in authentication systems, and gesture as a
      carrier of behavior characteristics has the advantages of being difficult to
      imitate and containing abundant information. This research aims to use three
      dimensional (3D) depth information of gesture movement to perform authentication
      with less user effort. We propose an approach based on depth cameras, which
      satisfies three requirements: Can authenticate from a single, customized gesture;
      achieves high accuracy without an excessive number of gestures for training; and
      continues learning the gesture during use of the system. To satisfy these
      requirements respectively: We use a sparse autoencoder to memorize the single
      gesture; we employ data augmentation technology to solve the problem of
      insufficient data; and we use incremental learning technology for allowing the
      system to memorize the gesture incrementally over time. An experiment has been
      performed on different gestures in different user situations that demonstrates
      the accuracy of one-class classification (OCC), and proves the effectiveness and
      reliability of the approach. Gesture authentication based on 3D depth cameras
      could be achieved with reduced user effort.

PMID- 30274188
TI  - Efficient Computation of Free Energy Surfaces of Diels-Alder Reactions in
      Explicit Solvent at Ab Initio QM/MM Level.
AB  - For Diels-Alder (DA) reactions in solution, an accurate and converged free energy
      (FE) surface at ab initio (ai) quantum mechanical/molecular mechanical (QM/MM)
      level is imperative for the understanding of reaction mechanism. However, this
      computation is still far too expensive. In a previous work, we proposed a new
      method termed MBAR+wTP, with which the computation of the ai FE profile can be
      accelerated by several orders of magnitude via a three-step procedure: (I) an
      umbrella sampling (US) using a semi-empirical (SE) QM/MM Hamiltonian is
      performed; (II) the FE profile is generated using the Multistate Bennett
      Acceptance Ratio (MBAR) analysis; and (III) a weighted Thermodynamic Perturbation
      (wTP) from the SE Hamiltonian to the ai Hamiltonian is performed to obtain the ai
      QM/MM FE profile using weight factors from the MBAR analysis. In this work, this
      method is extended to the calculations of two-dimensional FE surfaces of two
      Diels-Alder reactions of cyclopentadiene with either acrylonitrile or 1-4
      naphthoquinone at ai QM/MM level. The accurate activation free energies at the ai
      QM/MM level, which are much closer to the experimental measurements than those
      calculated by other methods, indicate that this MBAR+wTP method can be applied in
      the studies of complex reactions in condensed phase with much-enhanced
      efficiency.

PMID- 30274189
TI  - Genetic Variation and Alleviation of Salinity Stress in Barley (Hordeum vulgare
      L.).
AB  - Barley (Hordeum vulgare L.) represents one of the most important cereals
      cultivated worldwide. Investigating genetic variability and structure of barley
      is important for enhancing the crop productivity. This study aimed to investigate
      the diversity and structure of 40 barley genotypes originated from three European
      countries (France, the Netherlands, Poland) using amplified fragment length
      polymorphisms (AFLPs). It also aimed to study 5-aminolevulinic acid (ALA) effect
      on salinity tolerance of six barley genotypes. The expected heterozygosity (He)
      diverged from 0.126 to 0.501, with a mean of 0.348. Polymorphic information
      content (PIC) diverged from 0.103 to 0.482 across barley genotypes, with a mean
      of 0.316, indicating that barley genotypes are rich in a considerable level of
      genetic diversity. The 40 barley genotypes were further studied based on their
      geographical origin (Western Europe and Eastern Europe). The Eastern European
      region (Poland) has a higher barley variability than the Western European region
      (France and the Netherlands). Nei's distance-based cluster tree divided the 40
      barley accessions into two major clusters; one cluster comprised all the
      varieties originated from the Eastern European region, while the other major
      cluster included all accessions originated from the Western European region.
      Structure analysis results were in a complete concordance with our cluster
      analysis results. Slaski 2, Damseaux and Urbanowicki genotypes have the highest
      diversity level, whereas Carmen, Bigo and Cambrinus genotypes have the lowest
      level. The response of these six varieties to NaCl stress was also investigated.
      Salt stress (100 mM NaCl) slightly decreased levels of chlorophyll, carotenoid
      and osmolytes (proteins, soluble sugars, phenolics and flavonoids) in the leaves
      of Slaski 2, Damseaux and Urbanowicki genotypes at non-significant level, as
      compared to control samples. However, pigment contents and osmolytes in leaves of
      Carmen, Bigo and Cambrinus genotypes were significantly decreased by salt stress.
      Antioxidant enzyme activities were significantly increased in Slaski 2 genotype,
      but non-significantly increased in Carmen by salt stress. Priming Slaski 2 and
      Carmen cultivars with ALA under salt stress significantly induced pigment
      contents, antioxidants enzymes activity and stress-responsive genes expression,
      relative to NaCl-stressed plants. In conclusion, this study suggested a
      correlation between variability percentage and degree of salinity resistance. ALA
      improved salt tolerance in barley.

PMID- 30274190
TI  - Crystal Plasticity Modeling of Anisotropic Hardening and Texture Due to
      Dislocation Transmutation in Twinning.
AB  - In crystalline materials, dislocations are three-dimensional lattice distortions
      that systematically distort twin interfaces that they encounter. This results in
      dislocation dissociation events and changes in the atomic structure of the
      interface. The manner in which the interface distorts drive the product of the
      dissociation event, and consequently, the incident dislocation core and the
      magnitude and relative direction of the Burgers vector govern these slip-twin
      interaction phenomena. Recent characterization studies using transmission
      electron microscopy as well as advanced molecular dynamic simulations have shown
      that slip dislocations, whether striking or struck by a {10 1 - 2} twin boundary,
      dissociate into a combination of twinning disconnections, interfacial
      disclinations (facets), jogs, and other types of dislocations engulfed inside the
      twin domains, called transmuted dislocations. While twinning disconnections were
      found to promote twin propagation, the dislocations incorporated inside the twin
      are of considerable importance to hardening and damage initiation as they more
      significantly obstruct slip dislocations accommodating plasticity of the twins.
      In this work, the dislocation transmutation event and its effect on hardening is
      captured using a dislocation density based hardening model contained in a visco
      plastic self-consistent mean-field model. This is done by allowing the twins to
      increase their dislocation densities, not only by virtue of slip inside the twin,
      but also through dislocations that transmute from the parents as the twin volume
      fraction increases. A correspondence matrix rule is used to determine the type of
      converted dislocations while tracking and parameterizing their evolution. This
      hypothesis provides a modeling framework for capturing slip-twin interactions.
      The model is used to simulate the mechanical response of pure Mg and provides a
      more physically based approach for modeling stress-strain behavior.

PMID- 30274191
TI  - Damage Detection of Concrete-Filled Square Steel Tube (CFSST) Column Joints under
      Cyclic Loading Using Piezoceramic Transducers.
AB  - Concrete-filled square steel tube column (CFSSTC) joints are the most important
      parts of concrete-filled steel tube frame structures. It is of great significance
      to study the damage of CFSSTC joints under the seismic loads. In this paper,
      embedded piezoceramic transducers are used to monitor the damage of core concrete
      of CFSSTC joints under cyclic loading and surface-bonded piezoceramic disks are
      used to monitor the debonding damage of the steel tube and core concrete of two
      specimens. The damages of the joints under different loading levels and different
      loading cycles are evaluated by the received signal of the piezoceramic
      transducers. The experimental results show that the amplitude of the signal
      attenuates obviously with the appearance of damage in the joints, and the degree
      of attenuation increases with the development of the damage. The monitoring
      results from piezoceramic transducers are basically consistent with the
      hysteresis loops and skeleton curves of the CFSSTC joints during the cyclic
      loading. The effectiveness of the piezoceramic transducers are verified by the
      experimental results in structural health monitoring of the CFSSTC joint under
      cyclic loading.

PMID- 30274192
TI  - Galgeun-tang Attenuates Cigarette Smoke and Lipopolysaccharide Induced Pulmonary
      Inflammation via IkappaBalpha/NF-kappaB Signaling.
AB  - Galgeun-tang water extract (GGWE) is used to treat various diseases such as the
      common cold, eczema and asthma in China and Korea. In this study, we investigated
      the anti-inflammatory effect of GGWE using a cigarette smoke (CS)- and
      lipopolysaccharide (LPS)-induced induced pulmonary inflammation mouse model. The
      mice were exposed to CS for a total of seven days (eight cigarettes per day for 1
      h) and LPS was administered intranasally to mice on day 4. GGWE was administered
      by oral gavage at doses of 50 mg/kg or 100 mg/kg 1 h before exposure to CS. GGWE
      decreased inflammatory cell counts, and expression of inflammatory cytokines such
      as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) in
      bronchoalveolar lavage fluid (BALF) from mice exposed to CS and LPS. GGWE reduced
      the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2
      (COX-2), as well as the phosphorylation of inhibitor of kappa-B subunit alpha
      (IkappaBalpha) and nuclear factor kappa-B (NF-kappaB) in CS- and LPS-exposed
      mice. Histological examinations revealed that GGWE suppressed inflammatory cell
      infiltration into lung tissue compared to untreated CS- and LPS-exposed mice. In
      conclusion, GGWE effectively suppressed CS- and LPS-induced pulmonary
      inflammation. Our results indicate that GGWE may be used as a protective drug to
      control pulmonary inflammation diseases such as chronic obstructive pulmonary
      disease.

PMID- 30274194
TI  - Enhancing the Isolation and Performance of Control Planes for Fog Computing.
AB  - Fog computing, which places computing resources close to IoT devices, can offer
      low latency data processing for IoT applications. With software-defined
      networking (SDN), fog computing can enable network control logics to become
      programmable and run on a decoupled control plane, rather than on a physical
      switch. Therefore, network switches are controlled via the control plane.
      However, existing control planes have limitations in providing isolation and high
      performance, which are crucial to support multi-tenancy and scalability in fog
      computing. In this paper, we present optimization techniques for Linux to provide
      isolation and high performance for the control plane of SDN. The new techniques
      are (1) separate execution environment (SE2), which separates the execution
      environments between multiple control planes, and (2) separate packet processing
      (SP2), which reduces the complexity of the existing network stack in Linux. We
      evaluate the proposed techniques on commodity hardware and show that the maximum
      performance of a control plane increases by four times compared to the native
      Linux while providing strong isolation.

PMID- 30274193
TI  - Diet-Modulated Lipoprotein Metabolism and Vascular Inflammation Evaluated by 18F
      fluorodeoxyglucose Positron Emission Tomography.
AB  - Vascular inflammation plays a central role in atherosclerosis, from initiation
      and progression to acute thrombotic complications. Modified low-density
      lipoproteins (LDLs) and apoB-containing particles stimulate plaque inflammation
      by interacting with macrophages. Loss of function of high-density lipoprotein
      (HDL) for preventing LDL particles from oxidative modification in dyslipidemic
      states may amplify modified LDL actions, accelerating plaque inflammation. Diets
      are one of the most important factors that can affect these processes of
      lipoprotein oxidation and vascular inflammation. Recently, 18F-fluorodeoxyglucose
      (FDG) positron emission tomography (PET) has emerged as a reliable noninvasive
      imaging modality for identifying and quantifying vascular inflammation within
      atherosclerotic lesions based on the high glycolytic activity of macrophages
      infiltrating active atherosclerotic plaques. Vascular inflammation evaluated by
      FDG PET has been positively related to metabolic syndrome components and
      traditional risk factors of cardiovascular disease, including high-sensitivity C
      reactive protein, body mass index, and insulin resistance. A positive association
      of vascular inflammation with endothelial dysfunction, resistin levels,
      pericardial adipose tissue, and visceral fat area has also been reported. In
      contrast, HDL cholesterol and adiponectin have been inversely related to vascular
      inflammation detected by FDG PET. Because of its reproducibility, serial FDG PET
      shows potential for tracking the effects of dietary interventions and other
      systemic and local antiatherosclerotic therapies for plaque inflammation.

PMID- 30274195
TI  - Biocompatible Fe-Based Micropore Metal-Organic Frameworks as Sustained-Release
      Anticancer Drug Carriers.
AB  - Sustained-release preparation is a hot spot in antitumor drug research, where the
      first task is to select suitable drug carriers. Research has revealed that
      carboxylic acid iron metal-organic frameworks (MOFs), constructed from iron (Fe)
      ions and terephthalic acid, are nontoxic and biocompatible. Due to the breathing
      effect, the skeleton of this mesoporous material is flexible and can reversibly
      adapt its pore size through drug adsorption. Therefore, we chose one kind of Fe
      MOF, MIL-53(Fe), as a carrier for the anticancer drug oridonin (Ori). In this
      work, we report the design and synthesis of MIL-53(Fe) and explore its ability as
      a transport vehicle to deliver Ori. MIL-53(Fe) is characterized by scanning
      electron microscopy and X-ray powder diffraction. A loading capacity of 56.25 wt
      % was measured by high performance liquid chromatography. This carrier was safe
      and nontoxic (cell viability > 95.27%), depending on the results of 3-(4,5
      dimethylthiazol-2-yl)--2,5-diphenyltetrazolium bromide assays, lactate
      dehydrogenase assays, and Annexin V-fluoresce isothiocyanate/propidium iodide
      double-staining assays. After loading the drug, the structure of the MIL-53(Fe)
      was not destroyed, and Ori was amorphous in MIL-53(Fe). Based on an analysis of
      the Ori release profile, results suggest that it lasts for more than seven days
      in vitro. The cumulative release rate of Ori at the seventh day was about 82.23%
      and 91.75% in phosphate buffer saline solution at 37  degrees C under pH 7.2 and
      pH 5.5, respectively. HepG2 cells were chosen to study the cytotoxicity of
      Ori@MIL-53(Fe), and the results show that the anticancer ratio of Ori@MIL-53(Fe)
      system reaches 90.62%. Thus, MIL-53 can be used as a carrier for anticancer drugs
      and Ori@MIL-53(Fe) is a promising sustained-release drug delivery system for the
      cancer therapy.

PMID- 30274196
TI  - Negative Air Ions and Their Effects on Human Health and Air Quality Improvement.
AB  - Negative air ions (NAIs) have been discovered for more than 100 years and are
      widely used for air cleaning. Here, we have carried out a comprehensive reviewing
      on the effects of NAIs on humans/animals, and microorganisms, and plant
      development. The presence of NAIs is credited for increasing psychological
      health, productivity, and overall well-being but without consistent or reliable
      evidence in therapeutic effects and with controversy in anti-microorganisms.
      Reports also showed that NAIs could help people in relieving symptoms of
      allergies to dust, mold spores, and other allergens. Particulate matter (PM) is a
      major air pollutant that affects human health. Experimental data showed that NAIs
      could be used to high-efficiently remove PM. Finally, we have reviewed the plant
      based NAI release system under the pulsed electric field (PEF) stimulation. This
      is a new NAI generation system which releases a huge amount of NAIs under the PEF
      treatment. The system may be used to freshen indoor air and reduce PM
      concentration in addition to enriching oxygen content and indoor decoration at
      home, school, hospital, airport, and other indoor areas.

PMID- 30274197
TI  - Inhibitory Effects of Intranasal Administration of Insulin on Fat Oxidation
      during Exercise Are Diminished in Young Overweight Individuals.
AB  - It remains unknown whether the high insulin (INS) levels in the brain affect fat
      oxidation during exercise. We examined the effects of the intranasal
      administration of INS, which increases the INS concentration in the cerebrospinal
      fluid when peripheral effects are lacking, on the maximum fat oxidation rate
      (maxFOR) and its intensity (FATmax) during exercise in 15 young normal-weight (N
      group) and eight young overweight (O group) individuals. On two separate days,
      either INS or placebo (PL) was randomly administered intranasally before a graded
      exercise test. Indirect calorimetry was used to assess maxFOR and FATmax during
      exercise. Blood INS and glucose levels did not change after INS administration.
      In the N group, maxFOR and FATmax were significantly smaller in the INS trial
      than in the PL trial. MaxFOR was significantly smaller in the O group than in the
      N group and was not influenced by INS administration. Exercise-induced elevation
      in blood epinephrine levels tended to be reduced by INS administration only in
      the N group. Intranasal INS administration reduces fat oxidation during exercise
      without any peripheral effects, possibly by suppressing sympathetic nerve
      activity. This inhibitory effect is diminished in overweight subjects, suggesting
      that cerebral insulin effects are attenuated in this population.

PMID- 30274200
TI  - Impact of Consumption of Bananas on Attraction of Anopheles stephensi to Humans.
AB  - Humans vary in attractiveness to mosquitoes, a phenomenon that is largely
      attributed to differences in physical cues such as heat and volatile odors
      emanating from breath and skin. Diet can change human odors but whether specific
      dietary components alter host attractiveness is largely unexplored. We identified
      bananas as a target for study following a survey of the internet for advice on
      avoiding mosquito bites. Human attractiveness to Anopheles stephensi Liston was
      measured using a glass vial bioassay where mosquito contacts were measured before
      and 1-3 h after ingestion of bananas or grapes. Consumption of grapes had no
      effect on the number of contacts but banana ingestion resulted in a significant
      increase in the overall number of contacts in spite of individual variation that
      included some subjects who showed no effect or decreases in contacts. Further
      tests with a single volunteer showed that the effect was repeatable and
      consistent across 15 trials. The magnitude of the increase was not affected by
      the number of bananas eaten. Increased contact counts after banana ingestion were
      also observed when A. gambiae Giles was tested. These results support the
      hypothesis that diet plays an important role in mediating host attractiveness to
      anopheline mosquitoes.

PMID- 30274198
TI  - Quantitative Proteomics Analysis of Lettuce (Lactuca sativa L.) Reveals Molecular
      Basis-Associated Auxin and Photosynthesis with Bolting Induced by High
      Temperature.
AB  - Bolting is a key process in the growth and development of lettuce (Lactuca sativa
      L.). A high temperature can induce early bolting, which decreases both the
      quality and production of lettuce. However, knowledge of underlying lettuce
      bolting is still lacking. To better understand the molecular basis of bolting, a
      comparative proteomics analysis was conducted on lettuce stems, during the
      bolting period induced by a high temperature (33  degrees C) and a control
      temperature (20  degrees C) using iTRAQ-based proteomics, phenotypic measures,
      and biological verifications using qRT-PCR and Western blot. The high temperature
      induced lettuce bolting, while the control temperature did not. Of the 5454
      identified proteins, 619 proteins presented differential abundance induced by
      high-temperature relative to the control group, of which 345 had an increased
      abundance and 274 had a decreased abundance. Proteins with an abundance level
      change were mainly enriched in pathways associated with photosynthesis and
      tryptophan metabolism involved in auxin (IAA) biosynthesis. Moreover, among the
      proteins with differential abundance, proteins associated with photosynthesis and
      tryptophan metabolism were increased. These findings indicate that a high
      temperature enhances the function of photosynthesis and IAA biosynthesis to
      promote the process of bolting, which is in line with the physiology and
      transcription level of IAA metabolism. Our data provide a first comprehensive
      dataset for gaining novel understanding of the molecular basis underlying lettuce
      bolting induced by high temperature. It is potentially important for further
      functional analysis and genetic manipulation for molecular breeding to breed new
      cultivars of lettuce to restrain early bolting, which is vital for improving
      vegetable quality.

PMID- 30274201
TI  - Antimicrobial Coatings from Hybrid Nanoparticles of Biocompatible and
      Antimicrobial Polymers.
AB  - Hybrid nanoparticles of poly(methylmethacrylate) synthesized in the presence of
      poly (diallyldimethyl ammonium) chloride by emulsion polymerization exhibited
      good colloidal stability, physical properties, and antimicrobial activity but
      their synthesis yielded poor conversion. Here we create antimicrobial coatings
      from casting and drying of the nanoparticles dispersions onto model surfaces such
      as those of silicon wafers, glass coverslips, or polystyrene sheets and optimize
      conversion using additional stabilizers such as cetyltrimethyl ammonium bromide,
      dioctadecyldimethyl ammonium bromide, or soybean lecithin during nanoparticles
      synthesis. Methodology included dynamic light scattering, determination of
      wettability, ellipsometry of spin-coated films, scanning electron microscopy, and
      determination of colony forming unities (log CFU/mL) of bacteria after 1 h
      interaction with the coatings. The additional lipids and surfactants indeed
      improved nanoparticle synthesis, substantially increasing the conversion rates by
      stabilizing the monomer droplets in dispersion during the polymerization. The
      coatings obtained by spin-coating or casting of the nanoparticles dispersions
      onto silicon wafers were hydrophilic with contact angles increasing with the
      amount of the cationic polymer in the nanoparticles. Against Escherichia coli and
      Staphylococcus aureus, bacteria cell counts were reduced by approximately 7 logs
      upon interaction with the coatings, revealing their potential for several
      biotechnological and biomedical applications.

PMID- 30274199
TI  - Ocular Manifestations of Emerging Flaviviruses and the Blood-Retinal Barrier.
AB  - Despite flaviviruses remaining the leading cause of systemic human infections
      worldwide, ocular manifestations of these mosquito-transmitted viruses are
      considered relatively uncommon in part due to under-reporting. However, recent
      outbreaks of Zika virus (ZIKV) implicated in causing multiple ocular
      abnormalities, such as conjunctivitis, retinal hemorrhages, chorioretinal
      atrophy, posterior uveitis, optic neuritis, and maculopathies, has rejuvenated a
      significant interest in understanding the pathogenesis of flaviviruses, including
      ZIKV, in the eye. In this review, first, we summarize the current knowledge of
      the major flaviviruses (Dengue, West Nile, Yellow Fever, and Japanese
      Encephalitis) reported to cause ocular manifestations in humans with emphasis on
      recent ZIKV outbreaks. Second, being an immune privilege organ, the eye is
      protected from systemic infections by the presence of blood-retinal barriers
      (BRB). Hence, we discuss how flaviviruses modulate retinal innate response and
      breach the protective BRB to cause ocular or retinal pathology. Finally, we
      describe recently identified infection signatures of ZIKV and discuss whether
      these system biology-predicted genes or signaling pathways (e.g., cellular
      metabolism) could contribute to the pathogenesis of ocular manifestations and
      assist in the development of ocular antiviral therapies against ZIKV and other
      flaviviruses.

PMID- 30274204
TI  - Similarity of Data from Bee Bread with the Same Taxa Collected in India and
      Romania.
AB  - Bee Bread samples from Romania and India were analysed by microscopy and High
      Performance Liquid Chromatography with Diode Array Detection (HPLC/DAD) and
      compared with pollen from the correspondent taxa. The quantification of sugars,
      fructose/glucose ratio, total phenolics and flavonoids was also carried out. From
      the results was possible to identify Brassica and Eucalyptus samples that present
      similar HPLC/DAD profiles with the respective ultraviolet (UV) identification of
      the main compounds as Kaempferol-3-O-glycosides and Hydrocinnamic acid
      derivatives. The Fructose/Glucose (F/G) ratio and the total amounts of phenolics
      and flavonoids was in line with the prevalence of the specie identified. These
      coincident fingerprints gave the identification of the samples, as was previously
      proposed for bee pollens. This paper relates for the first time the achievement
      on the taxon carried out previously only for bee pollens. It was reported for the
      first time that this phenolic profile remains unchanged in the case of floral
      pollen (hand collected), bee pollen and bee bread. Despite the biochemical
      transformation that occurs during the fermentation of bee bread, it seems that
      these phenolic compounds are not affected and remain unchanged. Also, variables
      such as soil and climate do not seem to influence these compounds for the kind of
      samples under study.

PMID- 30274203
TI  - Role of Mitochondria in Regulating Lutein and Chlorophyll Biosynthesis in
      Chlorella pyrenoidosa under Heterotrophic Conditions.
AB  - The green alga Chlorella pyrenoidosa can accumulate lutein and chlorophyll under
      heterotrophic conditions. We propose that the mitochondrial respiratory electron
      transport chain (mRET) may be involved in this process. To verify this
      hypothesis, algal cells were treated with different mRET inhibitors. The
      biosynthesis of lutein and chlorophyll was found to be significantly stimulated
      by salicylhydroxamic acid (SHAM), whereas their contents substantially decreased
      after treatment with antimycin A and sodium azide (NaN3). Proteomic studies
      revealed profound protein alterations related to the redox and energy states, and
      a network was proposed: The up-regulation of peroxiredoxin reduces oxidized
      glutathione (GSSG) to reduced glutathione (GSH); phosphoenolpyruvate
      carboxykinase (PEPCK) catalyzes the conversion of oxaloacetic acid to
      phosphoenolpyruvate, and after entering the methylerythritol phosphate (MEP)
      pathway, 4-hydroxy-3-methylbut-2-en-1yl diphosphate synthase reduces 2-C-methyl-d
      erythritol-2,4-cyclodiphosphate (ME-Cpp) to 1-hydroxy-2-methyl-2-(E)-butenyl 4
      diphosphate (HMBPP), which is closely related to the synthesis of lutein; and
      coproporphyrinogen III oxidase and ChlI play important roles in the chlorophyll
      biosynthetic pathway. These results supported that for the heterotrophic C.
      pyrenoidosa, the signaling, oriented from mRET, may regulate the nuclear genes
      encoding the enzymes involved in photosynthetic pigment biosynthesis.

PMID- 30274205
TI  - Are Early Warning Scores Useful Predictors for Mortality and Morbidity in
      Hospitalised Acutely Unwell Older Patients? A Systematic Review.
AB  - BACKGROUND: Early warning scores (EWSs) are used to identify deteriorating
      patients for appropriate interventions. We performed a systematic review to
      examine the usefulness of EWSs in predicting inpatient mortality and morbidity
      (transfer to higher-level care and length of hospital stay) in older people
      admitted to acute medical units with sepsis, acute cardiovascular events, or
      pneumonia. METHODS: A systematic review of published and unpublished databases
      was conducted. Cochrane's tool for assessing Risk of Bias in Non-Randomised
      Studies-of Interventions (ROBINS-I) was used to appraise the evidence. A
      narrative synthesis was performed due to substantial heterogeneity. RESULTS: Five
      studies (n = 12,057) were eligible from 1033 citations. There was an overall
      "moderate" risk of bias for all studies. The predictive ability of EWSs regarding
      mortality was reported in one study (n = 274), suggesting EWSs were better at
      predicting survival, (negative predictive value >90% for all scores). Three
      studies (n = 1819) demonstrated a significant association between increasing
      modified EWSs (MEWSs) and increased risk of mortality. Hazards ratios for a
      composite death/intensive care (ICU) admission with MEWSs >=5 were significant in
      one study (p = 0.003). Two studies (n = 1421) demonstrated that a MEWS >=6 was
      associated with 21 times higher probability of mortality (95% Confidence Interval
      (CI): 2.71-170.57) compared with a MEWS <=1. A MEWS of >=5 was associated with 22
      times higher probability of mortality (95% CI: 10.45-49.16). CONCLUSION:
      Increasing EWSs are strongly associated with mortality and ICU admission in older
      acutely unwell patients. Future research should be targeted at better
      understanding the usefulness of high and increasing EWSs for specific acute
      illnesses in older adults.

PMID- 30274206
TI  - An Artificial Bee Colony-Based Green Routing Mechanism in WBANs for Sensor-Based
      E-Healthcare Systems.
AB  - At present, sensor-based E-Healthcare systems are attracting more and more
      attention from academia and industry. E-Healthcare systems are usually a Wireless
      Body Area Network (WBANs), which can monitor or diagnose human health by placing
      miniaturized, low-power sensor nodes in or on patient's bodies to measure various
      physiological parameters. However, in this process, WBAN nodes usually use
      batteries, and especially for implantable flexible nodes, it is difficult to
      accomplish the battery replacement, so the energy that the node can carry is very
      limited, making the efficient use of energy the most important problem to
      consider when designing WBAN routing algorithms. By considering factors such as
      residual energy of node, the importance level of nodes, path cost and path energy
      difference ratios, this paper gives a definition of Optimal Path of Energy
      Consumption (OPEC) in WBANs, and designs the Optimal Energy Consumption routing
      based on Artificial Bee Colony (ABC) for WBANs (OEABC). A performance simulation
      is carried out to verify the effectiveness of the OEABC. Simulation results
      demonstrate that compared with the genetic algorithm and ant colony algorithm,
      the proposed OEABC has a better energy efficiency and faster convergence rate.

PMID- 30274202
TI  - Molecular Mechanisms of Hepatocarcinogenesis Following Sustained Virological
      Response in Patients with Chronic Hepatitis C Virus Infection.
AB  - Despite the success of direct-acting antiviral (DAA) agents in treating chronic
      hepatitis C virus (HCV) infection, the number of cases of HCV-related
      hepatocellular carcinoma (HCC) is expected to increase over the next five years.
      HCC develops over the span of decades and is closely associated with fibrosis
      stage. HCV both directly and indirectly establishes a pro-inflammatory
      environment favorable for viral replication. Repeated cycles of cell death and
      regeneration lead to genomic instability and loss of cell cycle control. DAA
      therapy offers >90% sustained virological response (SVR) rates with fewer side
      effects and restrictions than interferon. While elimination of HCV helps to
      restore liver function and reverse mild fibrosis, post-SVR patients remain at
      elevated risk of HCC. A series of studies reporting higher than expected rates of
      HCC development among DAA-treated patients ignited debate over whether use of
      DAAs elevates HCC risk compared to interferon. However, recent prospective and
      retrospective studies based on larger patient cohorts have found no significant
      difference in risk between DAA and interferon therapy once other factors are
      taken into account. Although many mechanisms and pathways involved in
      hepatocarcinogenesis have been elucidated, our understanding of drivers specific
      to post-SVR hepatocarcinogenesis is still limited, and lack of suitable in vivo
      and in vitro experimental systems has hampered efforts to examine etiology
      specific mechanisms that might serve to answer this question more thoroughly.
      Further research is needed to identify risk factors and biomarkers for post-SVR
      HCC and to develop targeted therapies based on more complete understanding of the
      molecules and pathways implicated in hepatocarcinogenesis.

PMID- 30274208
TI  - How and When Are Job Crafters Engaged at Work?
AB  - The importance of work engagement and the lack of engaged employees have led
      researchers to focus on how to enhance employees' levels of engagement in the
      workplace. Although job crafting as a principal driver of work engagement has
      recently received much attention from academics, little is known about the
      processes and conditions in which employees who craft their tasks become engaged.
      In order to address these research gaps, we hypothesize that psychological
      capital (PsyCap) is likely to mediate the association between job crafting and
      work engagement, and that coworker support, rather than supervisor support, is
      likely to moderate the relationship between job crafting and PsyCap. Further, we
      integrated these hypotheses and tested the moderated mediation effect. Using
      survey data from 175 flight attendants in South Korea, we found the results to be
      in line with our expectations. The findings of this empirical research contribute
      to the understanding of how and when job crafters become engaged at work.

PMID- 30274210
TI  - A Magnetoencephalographic/Encephalographic (MEG/EEG) Brain-Computer Interface
      Driver for Interactive iOS Mobile Videogame Applications Utilizing the Hadoop
      Ecosystem, MongoDB, and Cassandra NoSQL Databases.
AB  - In Phase I, we collected data on five subjects yielding over 90% positive
      performance in Magnetoencephalographic (MEG) mid-and post-movement activity. In
      addition, a driver was developed that substituted the actions of the Brain
      Computer Interface (BCI) as mouse button presses for real-time use in visual
      simulations. The process was interfaced to a flight visualization demonstration
      utilizing left or right brainwave thought movement, the user experiences, the
      aircraft turning in the chosen direction, or on iOS Mobile Warfighter Videogame
      application. The BCI's data analytics of a subject's MEG brain waves and flight
      visualization performance videogame analytics were stored and analyzed using the
      Hadoop Ecosystem as a quick retrieval data warehouse. In Phase II portion of the
      project involves the Emotiv Encephalographic (EEG) Wireless Brain-Computer
      interfaces (BCIs) allow for people to establish a novel communication channel
      between the human brain and a machine, in this case, an iOS Mobile
      Application(s). The EEG BCI utilizes advanced and novel machine learning
      algorithms, as well as the Spark Directed Acyclic Graph (DAG), Cassandra NoSQL
      database environment, and also the competitor NoSQL MongoDB database for housing
      BCI analytics of subject's response and users' intent illustrated for both
      MEG/EEG brainwave signal acquisition. The wireless EEG signals that were acquired
      from the OpenVibe and the Emotiv EPOC headset can be connected via Bluetooth to
      an iPhone utilizing a thin Client architecture. The use of NoSQL databases were
      chosen because of its schema-less architecture and Map Reduce computational
      paradigm algorithm for housing a user's brain signals from each referencing
      sensor. Thus, in the near future, if multiple users are playing on an online
      network connection and an MEG/EEG sensor fails, or if the connection is lost from
      the smartphone and the webserver due to low battery power or failed data
      transmission, it will not nullify the NoSQL document-oriented (MongoDB) or column
      oriented Cassandra databases. Additionally, NoSQL databases have fast querying
      and indexing methodologies, which are perfect for online game analytics and
      technology. In Phase II, we collected data on five MEG subjects, yielding over
      90% positive performance on iOS Mobile Applications with Objective-C and C++,
      however on EEG signals utilized on three subjects with the Emotiv wireless
      headsets and (n < 10) subjects from the OpenVibe EEG database the Variational
      Bayesian Factor Analysis Algorithm (VBFA) yielded below 60% performance and we
      are currently pursuing extending the VBFA algorithm to work in the time-frequency
      domain referred to as VBFA-TF to enhance EEG performance in the near future. The
      novel usage of NoSQL databases, Cassandra and MongoDB, were the primary main
      enhancements of the BCI Phase II MEG/EEG brain signal data acquisition, queries,
      and rapid analytics, with MapReduce and Spark DAG demonstrating future
      implications for next generation biometric MEG/EEG NoSQL databases.

PMID- 30274209
TI  - Examination of the Effect of Suitable Size of Shoes under the Second Metatarsal
      Head and Width of Shoes under the Fifth Metatarsal Head for the Prevention of
      Callus Formation in Healthy Young Women.
AB  - Excessive pressure and shear stress while walking cause a risk of callus
      formation, which eventually causes foot ulcers in patients with diabetes
      mellitus. Callus under the second metatarsal head (MTH) has been associated with
      increased shear stress/pressure ratios (SPR). Callus under the fifth MTH has been
      associated with increased peak shear stress (PSS). The purpose of this study is
      to examine whether the effect of the suitable size and width of shoes prevents
      diabetic foot ulcers under the second and fifth MTH. We measured the pressure and
      shear stress by testing three kinds of sizes and two types of width of shoes.
      Significant difference was not observed in the SPR under the second MTH among
      different sizes of shoes. However, the pressure and shear stress were
      significantly lower when putting on shoes of fit size compared with larger sizes.
      The PSS under the fifth MTH was significantly smaller when putting on shoes of
      fit width compared with those of narrow width. Wearing shoes of fit size and
      width has the potential to prevent callus formation by reducing the pressure and
      shear stress constituting SPR under the second MTH and PSS under the fifth MTH.

PMID- 30274211
TI  - Integration of GPS, Monocular Vision, and High Definition (HD) Map for Accurate
      Vehicle Localization.
AB  - Self-localization is a crucial task for intelligent vehicles. Existing
      localization methods usually require high-cost IMU (Inertial Measurement Unit) or
      expensive LiDAR sensors (e.g., Velodyne HDL-64E). In this paper, we propose a low
      cost yet accurate localization solution by using a custom-level GPS receiver and
      a low-cost camera with the support of HD map. Unlike existing HD map-based
      methods, which usually requires unique landmarks within the sensed range, the
      proposed method utilizes common lane lines for vehicle localization by using
      Kalman filter to fuse the GPS, monocular vision, and HD map for more accurate
      vehicle localization. In the Kalman filter framework, the observations consist of
      two parts. One is the raw GPS coordinate. The other is the lateral distance
      between the vehicle and the lane, which is computed from the monocular camera.
      The HD map plays the role of providing reference position information and
      correlating the local lateral distance from the vision and the GPS coordinates so
      as to formulate a linear Kalman filter. In the prediction step, we propose using
      a data-driven motion model rather than a Kinematic model, which is more adaptive
      and flexible. The proposed method has been tested with both simulation data and
      real data collected in the field. The results demonstrate that the localization
      errors from the proposed method are less than half or even one-third of the
      original GPS positioning errors by using low cost sensors with HD map support.
      Experimental results also demonstrate that the integration of the proposed method
      into existing ones can greatly enhance the localization results.

PMID- 30274207
TI  - The Main Determinants of Diabetes Mellitus Vascular Complications: Endothelial
      Dysfunction and Platelet Hyperaggregation.
AB  - Diabetes mellitus is a common disease that affects 3-5% of the general population
      in Italy. In some countries of northern Europe or in North America, it can even
      affect 6-8% of the population. Of great concern is that the number of cases of
      diabetes is constantly increasing, probably due to the increase in obesity and
      the sedentary nature of the population. According to the World Health
      Organization, in the year 2030 there will be 360 million people with diabetes,
      compared to 170 million in 2000. This has important repercussions on the lives of
      patients and their families, and on health systems that offer assistance to
      patients. In this review, we try to describe in an organized way the
      pathophysiological continuity between diabetes mellitus, endothelial dysfunction,
      and platelet hyperaggregation, highlighting the main molecular mechanisms
      involved and the interconnections.

PMID- 30274212
TI  - Collective Efficacy: Development and Validation of a Measurement Scale for Use in
      Public Health and Development Programmes.
AB  - Impact evaluations of water, sanitation, and hygiene interventions have
      demonstrated lower than expected health gains, in some cases due to low uptake
      and sustained adoption of interventions at a community level. These findings
      represent common challenges for public health and development programmes relying
      on collective action. One possible explanation may be low collective efficacy
      (CE)-perceptions regarding a group's ability to execute actions related to a
      common goal. The purpose of this study was to develop and validate a metric to
      assess factors related to CE. We conducted this research within a cluster
      randomised sanitation and hygiene trial in Amhara, Ethiopia. Exploratory and
      confirmatory factor analyses were carried out to examine underlying structures of
      CE for men and women in rural Ethiopia. We produced three CE scales: one each for
      men and women that allow for examinations of gender-specific mechanisms through
      which CE operates, and one 26-item CE scale that can be used across genders. All
      scales demonstrated high construct validity. CE factor scores were significantly
      higher for men than women, even among household-level male-female dyads. These CE
      scales will allow implementers to better design and target community-level
      interventions, and examine the role of CE in the effectiveness of community-based
      programming.

PMID- 30274213
TI  - The Effects of Autophagy and PI3K/AKT/m-TOR Signaling Pathway on the Cell-Cycle
      Arrest of Rats Primary Sertoli Cells Induced by Zearalenone.
AB  - A high concentration of Zearalenone (ZEA) will perturb the differentiation of
      germ cells, and induce a death of germ cells, but the toxic mechanism and
      molecular mechanism remain unclear. The Sertoli cells (SCs) play an irreplaceable
      role in spermatogenesis. In order to explore the potential mechanism of ZEA male
      reproductive toxicity, we studied the effects of ZEA on cell proliferation, cell
      cycle distribution, cell-cycle-related proteins and autophagy-related pathway the
      PI3K/Akt/mTOR signaling in primary cultured rats SCs, and the effects of
      autophagy and PI3K/AKT/m TOR signaling pathway on the SCs cell-cycle arrest
      induced by ZEA treated with the autophagy promoter RAPA, autophagy inhibitor CQ,
      and the PI3K inhibitor LY294002, respectively. The data revealed that ZEA could
      inhibit the proliferation of SCs by arresting the cell cycle in the G2/M phase
      and trigger the autophagy via inhibiting the PI3K/Akt/m TOR signaling pathway.
      Promoting or inhibiting the level of autophagy could either augment or reverse
      the arrest of cell cycle. And it was regulated by PI3K/Akt/m TOR signaling
      pathway. Taken together, this study provides evidence that autophagy and
      PI3K/Akt/m TOR signaling pathway are involved in regulating rats primary SCs cell
      cycle arrest due to ZEA in vitro. To some extent, ZEA-induced autophagy plays a
      protective role in this process.

PMID- 30274216
TI  - Real-Time Monitoring of Tetraselmis suecica in A Saline Environment as Means of
      Early Water Pollution Detection.
AB  - Biological water pollution, including organic pollutants and their possible
      transportation, via biofouling and ballast water, has the potential to cause
      severe economic and health impacts on society and environment. Current water
      pollution monitoring methods are limited by transportation of samples to the
      laboratory for analysis, which could take weeks. There is an urgent need for a
      water quality monitoring technique that generates real-time data. The study aims
      to assess the feasibility of three sensing techniques to detect and monitor the
      concentrations of the model species Tetraselmis suecica in real-time using eleven
      samples for each method. Results showed UV-Vis spectrophotometer detected
      increasing concentration of Tetraselmis suecica with R2 = 0.9627 and R2 = 0.9672,
      at 450 nm and 650 nm wavelengths, respectively. Secondly, low-frequency
      capacitance measurements showed a linear relationship with increasing
      concentration of Tetraselmis suecica at 150 Hz (R2 = 0.8463) and 180 Hz (R2 =
      0.8391). Finally, a planar electromagnetic wave sensor measuring the reflected
      power S11 amplitude detected increasing cell density at 4 GHz (R2 = 0.8019).

PMID- 30274214
TI  - Interactions between Triterpenes and a P-I Type Snake Venom Metalloproteinase:
      Molecular Simulations and Experiments.
AB  - Small molecule inhibitors of snake venom metalloproteinases (SVMPs) could provide
      a means to rapidly halt the progression of local tissue damage following viperid
      snake envenomations. In this study, we examine the ability of candidate compounds
      based on a pentacyclic triterpene skeleton to inhibit SVMPs. We leverage
      molecular dynamics simulations to estimate the free energies of the candidate
      compounds for binding to BaP1, a P-I type SVMP, and compare these results with
      experimental assays of proteolytic activity inhibition in a homologous enzyme
      (Batx-I). Both simulation and experiment suggest that betulinic acid is the most
      active candidate, with the simulations predicting a standard binding free energy
      of Delta G ? = - 11.0 +/- 1.4 kcal/mol. The simulations also reveal the atomic
      interactions that underlie binding between the triterpenic acids and BaP1, most
      notably the electrostatic interaction between carboxylate groups of the compounds
      and the zinc cofactor of BaP1. Together, our simulations and experiments suggest
      that occlusion of the S1 ' subsite is essential for inhibition of proteolytic
      activity. While all active compounds make hydrophobic contacts in the S1 ' site,
      beta -boswellic acid, with its distinct carboxylate position, does not occlude
      the S1 ' site in simulation and exhibits negligible activity in experiment.

PMID- 30274215
TI  - The Association between Nonalcoholic Fatty Liver Disease and CT-Measured Skeletal
      Muscle Mass.
AB  - A relationship between nonalcoholic fatty liver disease (NAFLD) and sarcopenia
      has been suggested. The aim of this study was to evaluate the association between
      NAFLD and skeletal muscle mass measured by computed tomography (CT). The clinical
      records of individuals visiting our center for a routine health check-up who
      underwent abdominal ultrasonography and abdominal CT scanning were
      retrospectively reviewed. Sarcopenia was diagnosed according to body mass index
      (BMI)-adjusted skeletal muscle mass, which was measured by CT (CT-measured
      skeletal muscle index (SMICT)). Of the 1828 subjects (1121 males; mean age 54.9
      +/- 9.5 years), 487 (26.6%) were obese (BMI >= 25 kg/m2), and 454 (24.8%) had low
      muscle mass. Sarcopenic subjects had a significantly higher prevalence of NAFLD
      than nonsarcopenic subjects, regardless of obesity (35.9% vs. 26.8%, p = 0.004 in
      the nonobese group; 76.6% vs. 63.0%, p = 0.003 in the obese group). Sarcopenia
      was significantly associated with the risk of NAFLD (adjusted odds ratio (OR)
      (95% confidence interval (CI)), 1.51 (1.15-1.99)), and the risk of NAFLD
      increased with increasing severity of sarcopenia (adjusted OR (95% CI), 1.45
      (1.09-1.92) vs. 2.51 (1.16-5.56), mild vs. severe sarcopenia, respectively). When
      the risk of NAFLD was analyzed according to the SMICT quartiles, the adjusted OR
      and 95% CI for the lowest muscle mass quartile compared to the highest were 1.78
      (1.17-2.72) in males and 2.39 (1.13-5.37) in females. Low skeletal muscle mass,
      which was precisely measured by CT, is independently associated with NAFLD,
      suggesting that sarcopenia is a risk factor for NAFLD.

PMID- 30274217
TI  - Void Hole Avoidance for Reliable Data Delivery in IoT Enabled Underwater Wireless
      Sensor Networks.
AB  - Due to the limited availability of battery power of the acoustic node, an
      efficient utilization is desired. Additionally, the aquatic environment is harsh;
      therefore, the battery cannot be replaced, which leaves the network prone to
      sudden failures. Thus, an efficient node battery dissipation is required to
      prolong the network lifespan and optimize the available resources. In this paper,
      we propose four schemes: Adaptive transmission range in WDFAD-Depth-Based Routing
      (DBR) (A-DBR), Cluster-based WDFAD-DBR (C-DBR), Backward transmission-based WDFAD
      DBR (B-DBR) and Collision Avoidance-based WDFAD-DBR (CA-DBR) for Internet of
      Things-enabled Underwater Wireless Sensor Networks (IoT, UWSNs). A-DBR adaptively
      adjusts its transmission range to avoid the void node for forwarding data packets
      at the sink, while C-DBR minimizes end-to-end delay along with energy consumption
      by making small clusters of nodes gather data. In continuous transmission range
      adjustment, energy consumption increases exponentially; thus, in B-DBR, a fall
      back recovery mechanism is used to find an alternative route to deliver the data
      packet at the destination node with minimal energy dissipation; whereas, CA-DBR
      uses a fall back mechanism along with the selection of the potential node that
      has the minimum number of neighbors to minimize collision on the acoustic
      channel. Simulation results show that our schemes outperform the baseline
      solution in terms of average packet delivery ratio, energy tax, end-to-end delay
      and accumulated propagation distance.

PMID- 30274218
TI  - Highly-Ordered PdIn Intermetallic Nanostructures Obtained from Heterobimetallic
      Acetate Complex: Formation and Catalytic Properties in Diphenylacetylene
      Hydrogenation.
AB  - Formation of PdIn intermetallic nanoparticles supported on alpha-Al2O3 was
      investigated by X-ray powder diffraction (XRD), transmission electron microscopy
      (TEM), and hydrogen temperature-programmed desorption (H2-TPD) methods. The
      metals were loaded as heterobimetallic Pd(MU-O2CMe)4In(O2CMe) complex to ensure
      intimate contact between Pd and In. Reduction in H2 at 200  degrees C resulted in
      Pd-rich PdIn alloy as evidenced by XRD and the disappearance of Pd hydride. A
      minor amount of Pd1In1 intermetallic phase appeared after reduction at 200 
      degrees C and its formation was accomplished at 400  degrees C. Neither
      monometallic Pd or in nor other intermetallic structures were found after
      reduction at 400-600  degrees C. Catalytic performance of Pd1In1/alpha-Al2O3 was
      studied in the selective liquid-phase diphenylacetylene (DPA) hydrogenation. It
      was found that the reaction rate of undesired alkene hydrogenation is strongly
      reduced on Pd1In1 nanoparticles enabling effective kinetic control of the
      hydrogenation, and the catalyst demonstrated excellent selectivity to alkene.

PMID- 30274219
TI  - Dinophysis acuta in Scottish Coastal Waters and Its Influence on Diarrhetic
      Shellfish Toxin Profiles.
AB  - Diarrhetic shellfish toxins produced by the dinoflagellate genus Dinophysis are a
      major problem for the shellfish industry worldwide. Separate species of the genus
      have been associated with the production of different analogues of the okadaic
      acid group of toxins. To evaluate the spatial and temporal variability of
      Dinophysis species and toxins in the important shellfish-harvesting region of the
      Scottish west coast, we analysed data collected from 1996 to 2017 in two
      contrasting locations: Loch Ewe and the Clyde Sea. Seasonal studies were also
      undertaken, in Loch Ewe in both 2001 and 2002, and in the Clyde in 2015.
      Dinophysis acuminata was present throughout the growing season during every year
      of the study, with blooms typically occurring between May and September at both
      locations. The appearance of D. acuta was interannually sporadic and, when
      present, was most abundant in the late summer and autumn. The Clyde field study
      in 2015 indicated the importance of a temperature front in the formation of a D.
      acuta bloom. A shift in toxin profiles of common mussels (Mytilus edulis) tested
      during regulatory monitoring was evident, with a proportional decrease in okadaic
      acid (OA) and dinophysistoxin-1 (DTX1) and an increase in dinophysistoxin-2
      (DTX2) occurring when D. acuta became dominant. Routine enumeration of Dinophysis
      to species level could provide early warning of potential contamination of
      shellfish with DTX2 and thus determine the choice of the most suitable kit for
      effective end-product testing.

PMID- 30274220
TI  - Expression Analysis of the Prolific Candidate Genes, BMPR1B, BMP15, and GDF9 in
      Small Tail Han Ewes with Three Fecundity (FecB Gene) Genotypes.
AB  - The expression characteristics of the prolific candidate genes, BMPR1B, BMP15,
      and GDF9, in the major visceral organs and hypothalamic-pituitary-gonadal (HPG)
      axis tissues of three FecB genotypes (FecB BB, FecB B+, and FecB ++) were
      explored in STH ewes using RT-PCR and qPCR. The results were as follows, BMPR1B
      was expressed in all FecB BB genotype (Han BB) tissues, and GDF9 was expressed in
      all selected tissues, but BMP15 was specifically expressed in the ovaries.
      Further study of ovarian expression indicated that there was no difference in
      BMPR1B expression between genotypes, but the FecB B+ genotype (Han B+) had
      greater expression of GDF9 and BMP15 than Han BB and FecB ++ genotype (Han ++) (p
      < 0.05, p < 0.01). BMP15 expression was lower in the ovaries of Han BB than in
      Han ++ sheep, but the reverse was shown for GDF9. The gene expression in non
      ovarian tissues was also different between genotypes. Therefore, we consider that
      the three genes have an important function in ovine follicular development and
      maturation. This is the first systematic analysis of the tissue expression
      pattern of BMPR1B, BMP15, and GDF9 genes in STH sheep of the three FecB
      genotypes. These results contribute to the understanding of the molecular
      regulatory mechanism for ovine reproduction.

PMID- 30274221
TI  - Accelerometric Trunk Sensors to Detect Changes of Body Positions in Immobile
      Patients.
AB  - Mobilization, verticalization and position change are mandatory for severely
      affected neurological patients in early neurorehabilitation in order to improve
      neurological status and prevent complications. However, with the exception of
      hospitals and rehabilitation facilities, this activity is not usually monitored
      and so far the automated monitoring of position changes in immobile patients has
      not been investigated. Therefore, we investigated whether accelerometers on the
      upper trunk could reliably detect body position changes in immobile patients.
      Thirty immobile patients in early neurorehabilitation (Barthel Index <= 30) were
      enrolled. Two tri-axial accelerometers were placed on the upper trunk and on the
      thigh. Information on the position and position changes of the subject were
      derived from accelerometer data and compared to standard written documentation in
      the hospital over 24 h. Frequency and duration of different body positions
      (supine, sidelying, sitting) were measured. Data are presented as mean +/- SEM.
      Groups were compared using one-way ANOVA or Kruskal-Wallis-test. Differences were
      considered significant if p < 0.05. Trunk sensors detected 100% and thigh sensors
      66% of position changes (p = 0.0004) compared to standard care documentation.
      Furthermore, trunk recording also detected additional spontaneous body position
      changes that were not documented in standard care (81.8 +/- 4.4% of all position
      changes were documented in standard care documentation) (p < 0.0001). We found
      that accelerometric trunk sensors are suitable for recording position changes and
      mobilization of severely affected patients. Our findings suggest that using
      accelerometers for care documentation is useful for monitoring position changes
      and mobilization frequencies in and outside of hospital for severely affected
      neurological patients. Accelerometric sensors may be valuable in monitoring
      continuation of care plans after intensive neurorehabilitation.

PMID- 30274222
TI  - Configuration Optimization Design of Ti6Al4V Lattice Structure Formed by SLM.
AB  - Previous studies have revealed the influence of various lattice structures on the
      material density and mechanical properties. However, the majority of the
      topologies that are considered as study objects directly refer to metal/non
      crystal lattice cell configurations. Therefore, this paper proposes a
      configuration generation approach for generating a lattice structure, which can
      obtain a lattice configuration that enjoys the advantages of both ultra-low
      weight and favorable mechanical properties. Based on this approach, a new type of
      face-centered cubic lattice (all face-centered cubic, AFCC) structure with
      comprehensively optimal properties in terms of mass and mechanical properties is
      obtained. The experimental samples are formed with Ti6Al4V by the selective laser
      melting (SLM) method. Quasi-static uniaxial compression performance experiments
      and finite element analysis (FEA) are conducted on an AFCC structure and the
      control group body-centered cubic (BCC) structure. The results demonstrates that
      our optimized AFCC lattice structure is superior to the BCC structure, with
      elastic modulus and yield limit increases of 143% and 120%, respectively. For the
      same degree of deformation, the energy absorbed increases approximately 2.4
      times. The AFCC demonstrates significant advantages in terms of its mechanical
      properties and anti-explosion impact resistance while maintaining favorable ultra
      low weight, which validates the hypothesis that the proposed configuration
      generation approach can provide guidance for the design and further research on
      ultra-light lattice structures in related fields.

PMID- 30274223
TI  - Estrogen Modulates Glycerol Permeability in Sertoli Cells through Downregulation
      of Aquaporin-9.
AB  - High 17beta-Estradiol (E2) levels are known to cause alterations of
      spermatogenesis and environments throughout the male reproductive tract. Sertoli
      cells (SCs) ensure an adequate environment inside the seminiferous tubule.
      Glycerol stands as essential for the maintenance of blood-testis barrier created
      by SCs, however, the role of E2 in this process is not known. Herein, we
      hypothesized that the effect of E2 on glycerol permeability in mouse SCs (mSCs)
      could be mediated by aquaglyceroporins. The expression of aquaglyceroporins was
      assessed by RT-PCR and qRT-PCR. Glycerol permeability was evaluated by stopped
      flow light scattering. We were able to identify the expression of AQP3 and AQP9
      in mSCs where AQP9 is more abundant than AQP3. Our results show that high E2
      levels decrease AQP9 mRNA abundance with no influence on AQP3 in mSCs.
      Interestingly, high E2 levels decreased mSCs' permeability to glycerol, while
      downregulating AQP9 expression, thus suggesting a novel mechanism by which E2
      modulates fluid secretion in the testis. In conclusion, E2 is an important
      regulator of mSCs physiology and secretion through changes in AQP9 expression and
      function. Thus, alterations in glycerol permeability induced by E2 may be the
      cause for male infertility in cases associated with the presence of high E2
      levels.

PMID- 30274225
TI  - Glassy Carbon: A Promising Material for Micro- and Nanomanufacturing.
AB  - When certain polymers are heat-treated beyond their degradation temperature in
      the absence of oxygen, they pass through a semi-solid phase, followed by the loss
      of heteroatoms and the formation of a solid carbon material composed of a three
      dimensional graphenic network, known as glassy (or glass-like) carbon. The
      thermochemical decomposition of polymers, or generally of any organic material,
      is defined as pyrolysis. Glassy carbon is used in various large-scale industrial
      applications and has proven its versatility in miniaturized devices. In this
      article, micro and nano-scale glassy carbon devices manufactured by (i) pyrolysis
      of specialized pre-patterned polymers and (ii) direct machining or etching of
      glassy carbon, with their respective applications, are reviewed. The prospects of
      the use of glassy carbon in the next-generation devices based on the material's
      history and development, distinct features compared to other elemental carbon
      forms, and some large-scale processes that paved the way to the state-of-the-art,
      are evaluated. Selected support techniques such as the methods used for surface
      modification, and major characterization tools are briefly discussed. Barring
      historical aspects, this review mainly covers the advances in glassy carbon
      device research from the last five years (2013-2018). The goal is to provide a
      common platform to carbon material scientists, micro/nanomanufacturing experts,
      and microsystem engineers to stimulate glassy carbon device research.

PMID- 30274224
TI  - Dibasic Derivatives of Phenylcarbamic Acid against Mycobacterial Strains: Old
      Drugs and New Tricks?
AB  - In order to provide a more detailed view on the structure-antimycobacterial
      activity relationship (SAR) of phenylcarbamic acid derivatives containing two
      centers of protonation, 1-[2-[({[2-/3-(alkoxy)phenyl]amino}carbonyl)oxy]-3
      (dipropylammonio)propyl]pyrrolidinium oxalates (1a-d)/dichlorides (1e-h) as well
      as 1-[2-[({[2-/3-(alkoxy)phenyl]amino}carbonyl)oxy]-3-(di
      propylammonio)propyl]azepanium oxalates (1i-l)/dichlorides (1m-p; alkoxy = butoxy
      to heptyloxy) were physicochemically characterized by estimation of their surface
      tension (gamma; Traube's stalagmometric method), electronic features (log
      epsilon; UV/Vis spectrophotometry) and lipophilic properties (log kw; isocratic
      RP-HPLC) as well. The experimental log kw dataset was studied together with
      computational logarithms of partition coefficients (log P) generated by various
      methods based mainly on atomic or combined atomic and fragmental principles.
      Similarities and differences between the experimental and in silico lipophilicity
      descriptors were analyzed by unscaled principal component analysis (PCA). The in
      vitro activity of compounds 1a-p was inspected against Mycobacterium tuberculosis
      CNCTC My 331/88 (identical with H37Rv and ATCC 2794, respectively), M.
      tuberculosis H37Ra ATCC 25177, M. kansasii CNCTC My 235/80 (identical with ATCC
      12478), the M. kansasii 6509/96 clinical isolate, M. kansasii DSM 44162, M. avium
      CNCTC My 330/80 (identical with ATCC 25291), M. smegmatis ATCC 700084 and M.
      marinum CAMP 5644, respectively. In vitro susceptibility of the mycobacteria to
      reference drugs isoniazid, ethambutol, ofloxacin or ciprofloxacin was tested as
      well. A very unique aspect of the research was that many compounds from the set
      1a-p were highly efficient almost against all tested mycobacteria. The most
      promising derivatives showed MIC values varied from 1.9 MUM to 8 MUM, which were
      lower compared to those of used standards, especially if concerning ability to
      fight M. tuberculosis H37Ra ATCC 25177, M. kansasii DSM 44162 or M. avium CNCTC
      My 330/80. Current in vitro biological assays and systematic SAR studies based on
      PCA approach as well as fitting procedures, which were supported by relevant
      statistical descriptors, proved that the compounds 1a-p represented a very
      promising molecular framework for development of 'non-traditional' but effective
      antimycobacterial agents.

PMID- 30274226
TI  - User-Centred Healing-Oriented Conditions in the Design of Hospital Environments.
AB  - Design approaches towards energy efficient hospitals often result in a
      deteriorated indoor environmental quality, adverse health and comfort outcomes,
      and is a public health concern. This research presents an advanced approach to
      the design of a hospital environment based on a stimulative paradigm of healing
      to achieve not only healthy but also comforting conditions. A hospital room for
      severely burn patient was considered as one of the most demanding spaces. The
      healing environment was designed as a multi-levelled, dynamic process including
      the characteristics of users, building and systems. The developed integral user
      centred cyber-physical system (UCCPS) was tested in a test room and compared to
      the conventional system. The thermodynamic responses of burn patients, health
      care worker and visitor were simulated by using modified human body exergy
      models. In a healing environment, UCCPS enables optimal thermal balance,
      individually regulated according to the user specifics. For burn patient it
      creates optimal healing-oriented conditions with the lowest possible human body
      exergy consumption (hbExC), lower metabolic thermal exergy, lower sweat
      exhalation, evaporation, lower radiation and convection. For healthcare workers
      and visitors, thermally comfortable conditions are attained with minimal hbExC
      and neutral thermal load on their bodies. The information on this is an aid in
      integral hospital design, especially for future extensive renovations and
      environmental health actions.

PMID- 30274227
TI  - Quantitative Determination of Cd in Soil Using Laser-Induced Breakdown
      Spectroscopy in Air and Ar Conditions.
AB  - Rapid detection of Cd content in soil is beneficial to the prevention of soil
      heavy metal pollution. In this study, we aimed at exploring the rapid
      quantitative detection ability of laser- induced breakdown spectroscopy (LIBS)
      under the conditions of air and Ar for Cd in soil, and finding a fast and
      accurate method for quantitative detection of heavy metal elements in soil.
      Spectral intensity of Cd and system performance under air and Ar conditions were
      analyzed and compared. The univariate model and multivariate models of partial
      least-squares regression (PLSR) and least-squares support vector machine (LS-SVM)
      of Cd under the air and Ar conditions were built, and the LS-SVM model under the
      Ar condition obtained the best performance. In addition, the principle of
      influence of Ar on LIBS detection was investigated by analyzing the three
      dimensional profile of the ablation crater. The overall results indicated that
      LIBS combined with LS-SVM under the Ar condition could be a useful tool for the
      accurate quantitative detection of Cd in soil and could provide reference for
      environmental monitoring.

PMID- 30274228
TI  - A New Method for Predicting Erosion Damage of Suddenly Contracted Pipe Impacted
      by Particle Cluster via CFD-DEM.
AB  - A numerical study on the erosion of particle clusters in an abrupt pipe was
      conducted by means of the combined computational fluid dynamics (CFD) and
      discrete element methods (DEM). Furthermore, a particle-wall extrusion model and
      a criterion for judging particle collision interference were developed to
      classify and calculate the erosion rate caused by different interparticle
      collision mechanisms in a cluster. Meanwhile, a full-scale pipe flow experiment
      was conducted to confirm the effect of a particle cluster on the erosion rate and
      to verify the calculated results. The reducing wall was made of super 13Cr
      stainless steel materials and the round ceramsite as an impact particle was 0.65
      mm in diameter and 1850 kg/m3 in density. The results included an erosion depth,
      particle-wall contact parameters, and a velocity decay rate of colliding
      particles along the radial direction at the target surface. Subsequently, the
      effect of interparticle collision mechanisms on particle cluster erosion was
      discussed. The calculated results demonstrate that collision interference between
      particles during one cluster impact was more likely to appear on the surface with
      large particle impact angles. This collision process between the rebounded
      particles and the following particles not only consumed the kinetic energy but
      also changed the impact angle of the following particles.

PMID- 30274230
TI  - Observations of Turbulence in Free Atmosphere by Balloon-Borne Sensors.
AB  - In recent years, Thorpe analysis has been used to retrieve the characteristics of
      turbulence in free atmosphere from balloon-borne sensor data. However, previous
      studies have mainly focused on the mid-high latitude region, and this method is
      still rarely applied at heights above 30 km, especially above 35 km. Therefore,
      seven sets of upper air (>35 km) sounding data from the Changsha Sounding Station
      (28 degrees 12' N, 113 degrees 05' E), China are analyzed with Thorpe analysis in
      this article. It is noted that, in the troposphere, Thorpe analysis can better
      retrieve the turbulence distribution and the corresponding turbulence parameters.
      Also, because of the thicker troposphere at low latitudes, the values of the
      Thorpe scale L T and turbulent energy dissipation rate epsilon remain greater in
      a larger height range. In the stratosphere below the height of 35 km, the
      obtained epsilon is higher, and Thorpe analysis can only be used to analyze the
      characteristics of large-scale turbulence. In the stratosphere at a height of 35
      40 km, because of the interference of sensor noise, Thorpe analysis can only help
      to retrieve the rough distribution position of large-scale turbulence, while it
      can hardly help with the calculation of the turbulence parameters.

PMID- 30274231
TI  - Reply to Comment on Ultrasound Guidance for Botulinum Neurotoxin Chemodenervation
      Procedures. Toxins 2018, 10, 18-Quintessential Use of Ultrasound Guidance for
      Botulinum Toxin Injections.
AB  - We thank the authors for their detailed letter and salient comments related to
      our article on Ultrasound Guidance for botulinum toxin (BoNT) injections.[...].

PMID- 30274232
TI  - Biocompatible Coatings from Smart Biopolymer Nanoparticles for Enzymatically
      Induced Drug Release.
AB  - Nanoparticles can be used as a smart drug delivery system, when they release the
      drug only upon degradation by specific enzymes. A method to create such
      responsive materials is the formation of hydrogel nanoparticles, which have
      enzymatically degradable crosslinkers. Such hydrogel nanoparticles were prepared
      by ionotropic gelation sodium alginate with lysine-rich peptide sequences-either
      alpha-poly-L-lysine (PLL) or the aggrecanase-labile sequence KKKK-GRD
      ARGSV?NITEGE-DRG-KKKK. The nanoparticle suspensions obtained were analyzed by
      means of dynamic light scattering and nanoparticle tracking analysis. Degradation
      experiments carried out with the nanoparticles in suspension revealed enzyme
      induced lability. Drugs present in the polymer solution during the ionotropic
      gelation can be encapsulated in the nanoparticles. Drug loading was investigated
      for interferon-beta (IFN-beta) as a model, using a bioluminescence assay with
      MX2Luc2 cells. The encapsulation efficiency for IFN-beta was found to be
      approximately 25%. The nanoparticles suspension can be used to spray-coat
      titanium alloys (Ti-6Al-4V) as a common implant material. The coatings were
      proven by ellipsometry, reflection-absorption infrared spectroscopy, and X-ray
      photoelectron spectroscopy. An enzyme-responsive decrease in layer thickness is
      observed due to the degradation of the coatings. The Alg/peptide coatings were
      cytocompatible for human gingival fibroblasts (HGFIB), which was investigated by
      CellTiterBlue and lactate dehydrogenase (LDH) assay. However, HGFIBs showed poor
      adhesion and proliferation on the Alg/peptide coatings, but these could be
      improved by modification of the alginate with a RGD-peptide sequence. The smart
      drug release system presented can be further tailored to have the right release
      kinetics and cell adhesion properties.

PMID- 30274229
TI  - Redox Signaling of NADPH Oxidases Regulates Oxidative Stress Responses, Immunity
      and Aging.
AB  - An accumulating body of evidence suggests that transient or physiological
      reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidases act as a redox signal to re-establish homeostasis. The
      capacity to re-establish homeostasis progressively declines during aging but is
      maintained in long-lived animals to promote healthy aging. In the model organism
      Caenorhabditis elegans, ROS generated by dual oxidases (Duox) are important for
      extracellular matrix integrity, pathogen defense, oxidative stress resistance,
      and longevity. The Duox enzymatic activity is tightly regulated and under
      cellular control. Developmental molting cycles, pathogen infections, toxins,
      mitochondrial-derived ROS, drugs, and small GTPases (e.g., RHO-1) can activate
      Duox (BLI-3) to generate ROS, whereas NADPH oxidase inhibitors and negative
      regulators, such as MEMO-1, can inhibit Duox from generating ROS. Three
      mechanisms-of-action have been discovered for the Duox/BLI-3-generated ROS: (1)
      enzymatic activity to catalyze crosslinking of free tyrosine ethyl ester in
      collagen bundles to stabilize extracellular matrices, (2) high ROS bursts/levels
      to kill pathogens, and (3) redox signaling activating downstream kinase cascades
      to transcription factors orchestrating oxidative stress and immunity responses to
      re-establish homeostasis. Although Duox function at the cell surface is well
      established, recent genetic and biochemical data also suggests a novel role for
      Duoxs at the endoplasmic reticulum membrane to control redox signaling. Evidence
      underlying these mechanisms initiated by ROS from NADPH oxidases, and their
      relevance for human aging, are discussed in this review. Appropriately
      controlling NADPH oxidase activity for local and physiological redox signaling to
      maintain cellular homeostasis might be a therapeutic strategy to promote healthy
      aging.

PMID- 30274233
TI  - A Cross-Sectional Study of Experiences and Attitudes towards Clinical Audit of
      Farm Animal Veterinary Surgeons in the United Kingdom.
AB  - Clinical audit is a quality improvement tool used to assess and improve the
      clinical services provided to patients. This is the first study to investigate
      the extent to which clinical audit is understood and utilised in farm animal
      veterinary practice. A cross-sectional study to collect experiences and attitudes
      of farm animal veterinary surgeons in the UK towards clinical audit was conducted
      using an online nationwide survey. The survey revealed that whilst just under
      three-quarters (n = 237/325; 73%) of responding veterinary surgeons had heard of
      clinical audit, nearly 50% (n = 148/301) had never been involved in a clinical
      audit of any species. The participants' knowledge of what a clinical audit was
      varied substantially, with many respondents reporting not receiving training on
      clinical audit at the undergraduate or postgraduate level. Respondents that had
      participated in a clinical audit suggested that protected time away from clinical
      work was required for the process to be completed successfully. This novel study
      suggests that clinical audit is undertaken to some extent in farm animal practice
      and that practitioner perception is that it can bring benefits, but was felt that
      more resources and support were needed for it to be implemented successfully on a
      wider scale.

PMID- 30274235
TI  - Chemoresistance in H-Ferritin Silenced Cells: The Role of NF-kappaB.
AB  - Nuclear Factor-kappaB (NF-kappaB) is frequently activated in tumor cells
      contributing to aggressive tumor growth and resistance to chemotherapy. Here we
      demonstrate that Ferritin Heavy Chain (FHC) protein expression inversely
      correlates with NF-kappaB activation in cancer cell lines. In fact, FHC silencing
      in K562 and SKOV3 cancer cell lines induced p65 nuclear accumulation, whereas FHC
      overexpression correlated with p65 nuclear depletion in the same cell lines. In
      FHC-silenced cells, the p65 nuclear accumulation was reverted by treatment with
      the reactive oxygen species (ROS) scavenger, indicating that NF-kappaB activation
      was an indirect effect of FHC on redox metabolism. Finally, FHC knock-down in
      K562 and SKOV3 cancer cell lines resulted in an improved cell viability following
      doxorubicin or cisplatin treatment, being counteracted by the transient
      expression of inhibitory of NF-kappaB, IkappaBalpha. Our results provide an
      additional layer of information on the complex interplay of FHC with cellular
      metabolism, and highlight a novel scenario of NF-kappaB-mediated chemoresistance
      triggered by the downregulation of FHC with potential therapeutic implications.

PMID- 30274234
TI  - Whole-Genome Sequencing of 84 Japanese Eels Reveals Evidence against Panmixia and
      Support for Sympatric Speciation.
AB  - The Japanese eel (Anguilla japonica), European eel (Anguilla anguilla), and
      American eel (Anguilla rostrata) are migratory, catadromous, temperate zone fish
      sharing several common life cycle features. The population genetics of panmixia
      in these eel species has already been investigated. Our extensive population
      genetics analysis was based on 1400 Gb of whole-genome sequence (WGS) data from
      84 eels. It demonstrated that a Japanese eel group from the Kuma River differed
      from other populations of the same species. Even after removing the potential
      adapted/selected single nucleotide polymorphism (SNP) data, and with very small
      differences (fixation index [Fst] = 0.01), we obtained results consistently
      indicating that panmixia does not occur in Japanese eels. The life cycle of the
      Japanese eel is well-established and the Kuma River is in the center of its
      habitat. Nevertheless, simple reproductive isolation is not the probable cause of
      non-panmixia in this species. We propose that the combination of spawning area
      subdivision, philopatry, and habitat preference/avoidance accounts for the non
      panmixia in the Japanese eel population. We named this hypothesis the
      "reproductive isolation like subset mapping" (RISM) model. This finding may be
      indicative of the initial stages of sympatric speciation in these eels.

PMID- 30274237
TI  - A Label-Free Fluorescent DNA Calculator Based on Gold Nanoparticles for Sensitive
      Detection of ATP.
AB  - Herein we described a deoxyribonucleic acid (DNA) calculator for sensitive
      detection of the determination of adenosine triphosphate (ATP) using gold
      nanoparticles (GNP) and PicoGreen fluorescence dye as signal transducer, and ATP
      and single-stranded DNA (DNA-M') as activators. The calculator-related
      performances including linearity, reaction time, logic gate, and selectivity were
      investigated, respectively. The results revealed that this oligonucleotide sensor
      was highly sensitive and selective. The detection range was 50-500 nmol/L (R2 =
      0.99391) and the detection limit was 46.5 nmol/L. The AND DNA calculator was
      successfully used for the ATP detection in human urine. Compared with other
      methods, this DNA calculator has the characteristics of being label-free, non
      enzymic, simple, and highly sensitive.

PMID- 30274238
TI  - Validity of Capsule Endoscopy in Monitoring Therapeutic Interventions in Patients
      with Crohn's Disease.
AB  - Mucosal healing in Crohn's disease (CD) can be evaluated by capsule endoscopy
      (CE). However, only a few studies have utilized CE to demonstrate the therapeutic
      effect of medical treatment. We sought to evaluate the validity of using CE to
      monitor the effect of medical treatment in patients with CD. One hundred (n =
      100) patients with CD were enrolled. All patients had a gastrointestinal (GI)
      tract patency check prior to CE. Patients with baseline CE Lewis score (LS) <=
      135 were included in the non-active CD group and ended the study. In those with
      LS > 135 (active CD group), additional treatment was administered, regardless of
      symptoms, as per the treating clinician's advice. Patients of the active CD group
      underwent follow-up CE assessment 6 months later. Out of 92 patients with
      confirmed GI patency who underwent CE, 40 (43.4%) had CE findings of active
      inflammation. Of 29 patients with LS > 135 who received additional medications
      and underwent follow-up CE, improvement of the LS was noted in 23 (79.3%)
      patients. Eleven patients were asymptomatic but received additional medications;
      8 (72.7%) had improvement of the LS. This study demonstrated that additional
      treatment even for patients with CD in clinical remission and active small-bowel
      inflammation on CE can reduce mucosal damage.

PMID- 30274239
TI  - Sintering Behavior and Mechanical Properties of Mullite Fibers/Hydroxyapatite
      Ceramic.
AB  - The effect of fiber content and sintering temperature on sintering behavior and
      mechanical properties of mullite fibers/hydroxyapatite composites was studied.
      The composites were fabricated by hydrothermal synthesis and pressureless
      sintering. The amount of fibers was varied from 5 wt % to 15 wt % through
      hydrothermal synthesis, mullite fibers and hydroxyapatite composite powders were
      subsequently sintered at temperatures of 1150, 1250, and 1350  degrees C. The
      composites presented a more perturbed structure by increasing fiber content.
      Moreover, the composites experienced pore coalescence and exhibited a dense
      microstructure at elevated temperature. X-ray diffraction indicated that the
      composites underwent various chemical reactions and generated silicate glasses.
      The generation of silicate glasses increased the driving force of particle
      rearrangement and decreased the number of pores, which promoted densification of
      the composites. Densification typically leads to increased hardness and bending
      strength. The study proposes a densification mechanism and opens new insights
      into the sintering properties of these materials.

PMID- 30274236
TI  - The Interplay among PINK1/PARKIN/Dj-1 Network during Mitochondrial Quality
      Control in Cancer Biology: Protein Interaction Analysis.
AB  - PARKIN (E3 ubiquitin ligase PARK2), PINK1 (PTEN induced kinase 1) and DJ-1
      (PARK7) are proteins involved in autosomal recessive parkinsonism, and
      carcinogenic processes. In damaged mitochondria, PINK1's importing into the inner
      mitochondrial membrane is prevented, PARKIN presents a partial mitochondrial
      localization at the outer mitochondrial membrane and DJ-1 relocates to
      mitochondria when oxidative stress increases. Depletion of these proteins result
      in abnormal mitochondrial morphology. PINK1, PARKIN, and DJ-1 participate in
      mitochondrial remodeling and actively regulate mitochondrial quality control. In
      this review, we highlight that PARKIN, PINK1, and DJ-1 should be regarded as
      having an important role in Cancer Biology. The STRING database and Gene Ontology
      (GO) enrichment analysis were performed to consolidate knowledge of well-known
      protein interactions for PINK1, PARKIN, and DJ-1 and envisage new ones. The
      enrichment analysis of KEGG pathways showed that the PINK1/PARKIN/DJ-1 network
      resulted in Parkinson disease as the main feature, while the protein DJ-1 showed
      enrichment in prostate cancer and p53 signaling pathway. Some predicted
      transcription factors regulating PINK1, PARK2 (PARKIN) and PARK7 (DJ-1) gene
      expression are related to cell cycle control. We can therefore suggest that the
      interplay among PINK1/PARKIN/DJ-1 network during mitochondrial quality control in
      cancer biology may occur at the transcriptional level. Further analysis, like a
      systems biology approach, will be helpful in the understanding of PINK1/PARKIN/DJ
      1 network.

PMID- 30274240
TI  - Evidence of Mercury Methylation and Demethylation by the Estuarine Microbial
      Communities Obtained in Stable Hg Isotope Studies.
AB  - Microbial activity is a critical factor controlling methylmercury formation in
      aquatic environments. Microbial communities were isolated from sediments of two
      highly mercury-polluted areas of the Tagus Estuary (Barreiro and Cala do Norte)
      and differentiated according to their dependence on oxygen into three groups:
      aerobic, anaerobic, and sulphate-reducing microbial communities. Their potential
      to methylate mercury and demethylate methylmercury was evaluated through
      incubation with isotope-enriched Hg species (199HgCl and CH3201HgCl). The results
      showed that the isolated microbial communities are actively involved in
      methylation and demethylation processes. The production of CH3199Hg was
      positively correlated with sulphate-reducing microbial communities, methylating
      up to 0.07% of the added 199Hg within 48 h of incubation. A high rate of CH3201Hg
      degradation was observed and >20% of CH3201Hg was transformed. Mercury removal of
      inorganic forms was also observed. The results prove the simultaneous occurrence
      of microbial methylation and demethylation processes and indicate that
      microorganisms are mainly responsible for methylmercury formation and
      accumulation in the polluted Tagus Estuary.

PMID- 30274241
TI  - Effects of Jaw Periosteal Cells on Dendritic Cell Maturation.
AB  - Clinical application of tissue engineering products requires the exclusion of
      immune responses after implantation. We used jaw periosteal cells (JPCs) as a
      suitable stem cell source and analyzed herein the effects of JPCs on dendritic
      cell maturation after co-culturing of both cell types. Peripheral blood
      mononuclear cells (PBMCs) were differentiated to dendritic cells (DCs) by the
      addition of differentiation cocktails for 7 days in co-culture with
      undifferentiated and osteogenically induced JPCs. The effects of JPCs on DC
      maturation were analyzed at the beginning (day 7), in the middle (day 14), and at
      the end (day 21) of the osteogenesis process. We detected significantly lower DC
      numbers after co-culturing with JPCs that have previously been left untreated or
      osteogenically differentiated for 7, 14, and 21 days. Using gene expression
      analyses, significantly lower IL-12p35 and -p40 and pro-inflammatory cytokine
      (IFN-gamma and TNF-alpha) levels were detected, whereas IL-8 mRNA levels were
      significantly higher in DCs. Furthermore, osteogenic media conditions enhanced
      significantly IL-10 gene expression. We concluded that undifferentiated and
      osteogenically differentiated JPCs had an overall inhibiting influence on
      dendritic cell maturation. Further studies should clarify the underlaying
      mechanism in depth.

PMID- 30274242
TI  - Role of KCa3.1 Channels in Modulating Ca2+ Oscillations during Glioblastoma Cell
      Migration and Invasion.
AB  - Cell migration and invasion in glioblastoma (GBM), the most lethal form of
      primary brain tumors, are critically dependent on Ca2+ signaling. Increases of
      [Ca2+]i in GBM cells often result from Ca2+ release from the endoplasmic
      reticulum (ER), promoted by a variety of agents present in the tumor
      microenvironment and able to activate the phospholipase C/inositol 1,4,5
      trisphosphate PLC/IP3 pathway. The Ca2+ signaling is further strengthened by the
      Ca2+ influx from the extracellular space through Ca2+ release-activated Ca2+
      (CRAC) currents sustained by Orai/STIM channels, meant to replenish the partially
      depleted ER. Notably, the elevated cytosolic [Ca2+]i activates the intermediate
      conductance Ca2+-activated K (KCa3.1) channels highly expressed in the plasma
      membrane of GBM cells, and the resulting K+ efflux hyperpolarizes the cell
      membrane. This translates to an enhancement of Ca2+ entry through Orai/STIM
      channels as a result of the increased electromotive (driving) force on Ca2+
      influx, ending with the establishment of a recurrent cycle reinforcing the Ca2+
      signal. Ca2+ signaling in migrating GBM cells often emerges in the form of
      intracellular Ca2+ oscillations, instrumental to promote key processes in the
      migratory cycle. This has suggested that KCa3.1 channels may promote GBM cell
      migration by inducing or modulating the shape of Ca2+ oscillations. In
      accordance, we recently built a theoretical model of Ca2+ oscillations
      incorporating the KCa3.1 channel-dependent dynamics of the membrane potential,
      and found that the KCa3.1 channel activity could significantly affect the IP3
      driven Ca2+ oscillations. Here we review our new theoretical model of Ca2+
      oscillations in GBM, upgraded in the light of better knowledge of the KCa3.1
      channel kinetics and Ca2+ sensitivity, the dynamics of the Orai/STIM channel
      modulation, the migration and invasion mechanisms of GBM cells, and their
      regulation by Ca2+ signals.

PMID- 30274243
TI  - Ab Initio Molecular Dynamics Simulation Study on the Stereo Reactions between
      Atomic Oxygen Anion and Methane.
AB  - Ion-molecule reaction between atomic oxygen anion (O-) and methane (CH4) has been
      systematically investigated employing the on-the-fly ab initio molecular dynamics
      simulations. Besides the major H-abstraction process as the exothermic reaction
      studied widely, an endothermic pathway to produce OCH3- and H is also observed in
      this study. Three typical O- attack modes with reference to the pyramid structure
      of CH4 fixed in space have been considered. It was found that the internal
      motions of the radical products are significantly dependent on the O- attack
      modes. As for the reaction between O- and the thermally vibrating CH4, the major
      pathway to produce OH- and CH3 is preferred by the direct H-abstraction and the
      minor pathway to produce H and OCH3- is the roaming reaction via the transient
      negative ion [HO-CH3]-.

PMID- 30274244
TI  - Inflammation in Coronary Artery Ectasia Compared to Atherosclerosis.
AB  - We have read with great enthusiasm the article recently published by Boles et al.
      [...].

PMID- 30274247
TI  - Gender Identity Development among Teenagers Living in the Subarctic Region of
      Russia.
AB  - Gender identity is an important element of an individual's identity and is one of
      the regulators of human behavior while acquiring social roles. The aim of this
      empirical research is to study gender identity development among teenagers living
      in the subarctic territories of Russia. The results show the correlation between
      types of gender identity among male and female teenagers, the dynamic in the
      correlation between gender identity types during adolescence and the
      characteristics of each type of gender identity in adolescence from the point of
      view of psychological properties.

PMID- 30274246
TI  - Considerations of AOX Functionality Revealed by Critical Motifs and Unique
      Domains.
AB  - An understanding of the genes and mechanisms regulating environmental stress in
      crops is critical for boosting agricultural yield and safeguarding food security.
      Under adverse conditions, response pathways are activated for tolerance or
      resistance. In multiple species, the alternative oxidase (AOX) genes encode
      proteins which help in this process. Recently, this gene family has been
      extensively investigated in the vital crop plants, wheat, barley and rice.
      Cumulatively, these three species and/or their wild ancestors contain the genes
      for AOX1a, AOX1c, AOX1e, and AOX1d, and common patterns in the protein isoforms
      have been documented. Here, we add more information on these trends by
      emphasizing motifs that could affect expression, and by utilizing the most recent
      discoveries from the AOX isoform in Trypanosoma brucei to highlight clade
      dependent biases. The new perspectives may have implications on how the AOX gene
      family has evolved and functions in monocots. The common or divergent amino acid
      substitutions between these grasses and the parasite are noted, and the potential
      effects of these changes are discussed. There is the hope that the insights
      gained will inform the way future AOX research is performed in monocots, in order
      to optimize crop production for food, feed, and fuel.

PMID- 30274245
TI  - Regulation and Metabolic Significance of De Novo Lipogenesis in Adipose Tissues.
AB  - De novo lipogenesis (DNL) is a complex and highly regulated process in which
      carbohydrates from circulation are converted into fatty acids that are then used
      for synthesizing either triglycerides or other lipid molecules. Dysregulation of
      DNL contributes to human diseases such as obesity, type 2 diabetes, and
      cardiovascular diseases. Thus, the lipogenic pathway may provide a new
      therapeutic opportunity for combating various pathological conditions that are
      associated with dysregulated lipid metabolism. Hepatic DNL has been well
      documented, but lipogenesis in adipocytes and its contribution to energy
      homeostasis and insulin sensitivity are less studied. Recent reports have gained
      significant insights into the signaling pathways that regulate lipogenic
      transcription factors and the role of DNL in adipose tissues. In this review, we
      will update the current knowledge of DNL in white and brown adipose tissues with
      the focus on transcriptional, post-translational, and central regulation of DNL.
      We will also summarize the recent findings of adipocyte DNL as a source of some
      signaling molecules that critically regulate energy metabolism.

PMID- 30274248
TI  - Oncobox Bioinformatical Platform for Selecting Potentially Effective Combinations
      of Target Cancer Drugs Using High-Throughput Gene Expression Data.
AB  - Sequential courses of anticancer target therapy lead to selection of drug
      resistant cells, which results in continuous decrease of clinical response. Here
      we present a new approach for predicting effective combinations of target drugs,
      which act in a synergistic manner. Synergistic combinations of drugs may prevent
      or postpone acquired resistance, thus increasing treatment efficiency. We
      cultured human ovarian carcinoma SKOV-3 and neuroblastoma NGP-127 cancer cell
      lines in the presence of Tyrosine Kinase Inhibitors (Pazopanib, Sorafenib, and
      Sunitinib) and Rapalogues (Temsirolimus and Everolimus) for four months and
      obtained cell lines demonstrating increased drug resistance. We investigated gene
      expression profiles of intact and resistant cells by microarrays and analyzed
      alterations in 378 cancer-related signaling pathways using the bioinformatical
      platform Oncobox. This revealed numerous pathways linked with development of drug
      resistant phenotypes. Our approach is based on targeting proteins involved in as
      many as possible signaling pathways upregulated in resistant cells. We tested 13
      combinations of drugs and/or selective inhibitors predicted by Oncobox and 10
      random combinations. Synergy scores for Oncobox predictions were significantly
      higher than for randomly selected drug combinations. Thus, the proposed approach
      significantly outperforms random selection of drugs and can be adopted to enhance
      discovery of new synergistic combinations of anticancer target drugs.

PMID- 30274250
TI  - The Benefit of Anti-Inflammatory and Renal-Protective Dietary Ingredients on the
      Biological Processes of Aging in the Kidney.
AB  - One of the significant organ systems which decline in aging is the kidney. While
      the causes of age-associated decline in renal function are likely multifactorial,
      oxidative stress and inflammation are hypothesized to play important roles in the
      structural and functional changes of the kidney. During aging there is a general
      decline in the glomerular filtration rate (GFR), a primary measurement used to
      assess kidney function. Inflammation and oxidative stress have been hypothesized
      to have a significant detrimental effect on renal function in aging and this may
      be attenuated by renal protective dietary ingredients. These dietary ingredients
      may affect renal function directly or through a microbiome-mediated secondary
      product. Likewise, structural changes including renal tubular atrophy,
      interstitial fibrosis, and glomerulosclerosis have all been described in aging.
      Such detrimental changes may benefit from dietary ingredients that may delay or
      attenuate the occurrence of such changes. This review will describe the
      physiology and pathophysiology of aging in renal function with an emphasis on
      dogs and cats that develop a decline in kidney function naturally. In addition,
      the varying biomarkers of health and renal dysfunction will be discussed.
      Finally, we will evaluate the aid in the management of this normal decline
      through dietary intervention in animal models.

PMID- 30274249
TI  - eB4CAST: An Evidence-Based Tool to Promote Dissemination and Implementation in
      Community-Based, Public Health Research.
AB  - eB4CAST, evidence-Based forecast C-capture, A-assemble, S-sustain, T-timelessness
      (eB4CAST), framework was developed from existing dissemination and implementation
      (D & I) constructs as a dissemination tool to promote community-based program
      usability and future application in targeted populations. eB4CAST captures and
      transforms research findings into a dissemination report that shows program need
      and impact to endorse program continuation and expansion. This is achieved
      through direct and indirect data collection of community factors and program
      impact that can showcase the need for program sustainability and potential for
      future dissemination sites. Testimonials, individual feedback, and program
      process and outcomes contribute to the direct data while data collected from
      census, county, and state databases and reports allow for indirect information to
      be captured and analyzed. Capturing data in the two levels allow eB4CAST to
      forecast program need and highlight program impact through a footprint. eB4CAST
      framework for dissemination tool creation is organized into four sections:
      Capture, Assemble, Sustainability, and Timelessness. Capture encompasses the
      collection of indirect and direct data related to intervention goals. Assemble is
      the compilation of the data into a visually appealing and easily understood
      media. Sustainability encourages the use of dissemination tools to provide
      forecast of program need and footprint of program impact back to community
      participants, program leaders, and key stakeholders to endorse program
      sustainability. Lastly, timelessness encourages cyclic movement through these
      constructs to continue program monitoring and data sharing to ensure timeless
      program evaluation and conformation to change in needs. The eB4CAST framework
      provides a systematic method to capture justification of program need and impact
      of community-based research that can be modified to fit diverse public health
      interventions providing a necessary D & I tool.

PMID- 30274252
TI  - Relationship of Absolute and Relative Lower-Body Strength to Predictors of
      Athletic Performance in Collegiate Women Soccer Players.
AB  - The purpose of this study was to investigate the relationships between absolute
      and relative lower-body strength on predictors of athletic performance among
      Division II collegiate women's soccer players. Archived pre-season testing data
      for seventeen (n = 17) female National Collegiate Athletics Association (NCAA)
      Division II soccer players were analyzed, including: vertical jump, 3RM back
      squat, 505-agility, modified T-test, 10 m and 30 m sprint, and 20 m multistage
      fitness test (20 m MSFT). Relative strength was calculated based on the estimated
      1RM back squat divided by the athlete's body mass. Significant correlations were
      discovered between absolute lower-body strength and 505-agility (Right: r = 
      0.51, p < 0.05; Left: r = -0.59, p < 0.05), modified T-test (r = -0.55, p <
      0.05), 10 m and 30 m (r = -0.59, p < 0.05; r = -0.54, p < 0.05), and sprint
      performance. Relative lower-body strength showed significant correlations with
      vertical jump (r = 0.54, p < 0.05), 505-agility (Right: r = -0.58, p < 0.05;
      Left: r = -0.67, p < 0.01), modified T-test (r = -0.75, p < 0.01), 10 m and 30 m
      (r = -0.59 p < 0.05; r = -0.67, p < 0.01), and the 20 m MSFT (r = 0.58, p <
      0.05). These results indicate that strength and conditioning coaches should
      emphasize the development of absolute and relative lower-body strength with their
      players to improve power, agility, and speed performance.

PMID- 30274253
TI  - Serum 25-Hydroxyvitamin D and Diet Mediates Vaso-Occlusive Related
      Hospitalizations in Sickle-Cell Disease Patients.
AB  - Sickle cell disease (SCD) is a genetic disorder resulting from the presence of
      mutated hemoglobin S (HbS). Homozygous carriers will present with early
      manifestations of painful vaso-occlusive crises. SCD patients have been reported
      to be severely deficient in vitamin D (<20 ng/mL). Four years (2010-2014) of
      individual de-identified Sickle Cell Clinic of Southern Louisiana (SCCSL-SCD)
      patient records were analyzed for vitamin D status and the level of crisis
      related ER/hospital utilization. To determine the dietary, and behavioral
      mediators of SCD-crisis in our study population, a cohort of 102 SCCSL-SCD
      patients were administered a survey that evaluated sun exposure, dietary
      behaviors, and pain frequency and severity. Patients with circulating levels of
      25(OH)D3 less than 14.1 ng/mL reported having more crisis-related hospital visits
      per year (10) than patients with 25(OH)D3 serum levels >34 ng/mL. The result of
      the dietary survey detailed a relationship between patients who reported to have
      "Almost Never" consumed fish or milk in their diets and more frequent hospital
      stays and ER visits than those who reported consuming these products on a daily
      basis. Those who consumed these foods in their diet several times a month also
      had fewer ER visits when compared to the "Almost Never" category.

PMID- 30274254
TI  - Quantification and Confirmation of Fifteen Carbamate Pesticide Residues by
      Multiple Reaction Monitoring and Enhanced Product Ion Scan Modes via LC-MS/MS
      QTRAP System.
AB  - In this research, fifteen carbamate pesticide residues were systematically
      analyzed by ultra-high performance liquid chromatography-quadrupole-linear ion
      trap mass spectrometry on a QTRAP 5500 system in both multiple reaction
      monitoring (MRM) and enhanced product ion (EPI) scan modes. The carbamate
      pesticide residues were extracted from a variety of samples by QuEChERS method
      and separated by a popular reverse phase column (Waters BEH C18). Except for the
      current conformation criteria including selected ion pairs, retention time and
      relative intensities from MRM scan mode, the presence of carbamate pesticide
      residues in diverse samples, especially some doubtful cases, could also be
      confirmed by the matching of carbamate pesticide spectra via EPI scan mode.
      Moreover, the fragmentation routes of fifteen carbamates were firstly explained
      based on the mass spectra obtained by a QTRAP system; the characteristic fragment
      ion from a neutral loss of CH3NCO (-57 Da) could be observed. The limits of
      detection and quantification for fifteen carbamates were 0.2-2.0 MUg kg-1 and 0.5
      5.0 MUg kg-1, respectively. For the intra- (n = 3) and inter-day (n = 15)
      precisions, the recoveries of fifteen carbamates from spiked samples ranged from
      88.1% to 118.4%, and the coefficients of variation (CVs) were all below 10%. The
      method was applied to pesticide residues detection in fruit, vegetable and green
      tea samples taken from local markets, in which carbamates were extensively
      detected but all below the standard of maximum residue limit.

PMID- 30274251
TI  - Role of Mitogen Activated Protein Kinase Signaling in Parkinson's Disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder caused by insufficient
      dopamine production due to the loss of 50% to 70% of dopaminergic neurons. A
      shortage of dopamine, which is predominantly produced by the dopaminergic neurons
      within the substantia nigra, causes clinical symptoms such as reduction of muscle
      mass, impaired body balance, akinesia, bradykinesia, tremors, postural
      instability, etc. Lastly, this can lead to a total loss of physical movement and
      death. Since no cure for PD has been developed up to now, researchers using cell
      cultures and animal models focus their work on searching for potential
      therapeutic targets in order to develop effective treatments. In recent years,
      genetic studies have prominently advocated for the role of improper protein
      phosphorylation caused by a dysfunction in kinases and/or phosphatases as an
      important player in progression and pathogenesis of PD. Thus, in this review, we
      focus on the role of selected MAP kinases such as JNKs, ERK1/2, and p38 MAP
      kinases in PD pathology.

PMID- 30274256
TI  - Emerging Functions for Cell Wall Polysaccharides Accumulated during Eudicot Seed
      Development.
AB  - The formation of seeds is a reproductive strategy in higher plants that enables
      the dispersal of offspring through time and space. Eudicot seeds comprise three
      main components, the embryo, the endosperm and the seed coat, where the
      coordinated development of each is important for the correct formation of the
      mature seed. In addition, the seed coat protects the quiescent progeny and can
      provide transport mechanisms. A key underlying process in the production of seed
      tissues is the formation of an extracellular matrix termed the cell wall, which
      is well known for its essential function in cytokinesis, directional growth and
      morphogenesis. The cell wall is composed of a macromolecular network of polymers
      where the major component is polysaccharides. The attributes of polysaccharides
      differ with their composition and charge, which enables dynamic remodeling of the
      mechanical and physical properties of the matrix by adjusting their production,
      modification or turnover. Accordingly, the importance of specific polysaccharides
      or modifications is increasingly being associated with specialized functions
      within seed tissues, often through the spatio-temporal accumulation or remodeling
      of particular polymers. Here, we review the evolution and accumulation of
      polysaccharides during eudicot seed development, what is known of their impact on
      wall architecture and the diverse roles associated with these in different seed
      tissues.

PMID- 30274255
TI  - Antioxidant Activity and Phytochemical Characterization of Senecio clivicolus
      Wedd.
AB  - Antioxidant phytochemicals play a key role in oxidative stress control and in the
      prevention of related disorders, such as premature aging, degenerative diseases,
      diabetes, and cancer. The aim of this study was to investigate the potential
      antioxidant activity and the phytochemical profile of Senecio clivicolus Wedd., a
      perennial shrub, belonging to the Asteraceae family. Despite the wide interest of
      this family, this specie has not been investigated yet. S. clivicolus aerial
      parts were extracted with 96% ethanol. Then, the ethanol extract was fractionated
      by liquid/liquid extraction using an increasing solvents polarity. Total
      polyphenol and terpenoid contents were measured. Moreover, the antioxidant
      activity was evaluated by six different complementary in vitro assays. The
      Relative Antioxidant Capacity Index (RACI) was used to compare data obtained by
      different tests. The sample showing the highest RACI was subjected to
      characterization and quantitation of its phenolic composition using LC-MS/MS
      analysis. The ethyl acetate fraction, investigated by LC-MS/MS analysis, showed
      30 compounds, most of them are chlorogenic acid and flavonoid derivatives. To the
      best of our knowledge, this is the first report about the evaluation of
      antioxidant activity and phytochemical profile of S. clivicolus, underlying the
      importance of this species as a source of health-promoting phytochemicals.

PMID- 30274258
TI  - Fyn Regulates Binding Partners of Cyclic-AMP Dependent Protein Kinase A.
AB  - The cAMP-dependent protein kinase A (PKA) is a serine/threonine kinase involved
      in many fundamental cellular processes, including migration and proliferation.
      Recently, we found that the Src family kinase Fyn phosphorylates the catalytic
      subunit of PKA (PKA-C) at Y69, thereby increasing PKA kinase activity. We also
      showed that Fyn induced the phosphorylation of cellular proteins within the PKA
      preferred target motif. This led to the hypothesis that Fyn could affect proteins
      in complex with PKA. To test this, we employed a quantitative mass spectrometry
      approach to identify Fyn-dependent binding partners in complex with PKA-C. We
      found Fyn enhanced the binding of PKA-C to several cytoskeletal regulators that
      localize to the centrosome and Golgi apparatus. Three of these Fyn-induced PKA
      interactors, AKAP9, PDE4DIP, and CDK5RAP2, were validated biochemically and were
      shown to exist in complex with Fyn and PKA in a glioblastoma cell line.
      Intriguingly, the complexes formed between PKA-C and these known AKAPs were
      dependent upon Fyn catalytic activity and expression levels. In addition, we
      identified Fyn-regulated phosphorylation sites on proteins in complex with PKA-C.
      We also identified and biochemically validated a novel PKA-C interactor, LARP4,
      which complexed with PKA in the absence of Fyn. These results demonstrate the
      ability of Fyn to influence the docking of PKA to specific cellular scaffolds and
      suggest that Fyn may affect the downstream substrates targeted by PKA.

PMID- 30274257
TI  - Photodynamic Inactivation of Herpes Simplex Viruses.
AB  - Herpes simplex virus (HSV) infections can be treated with direct acting
      antivirals like acyclovir and foscarnet, but long-term use can lead to drug
      resistance, which motivates research into broadly-acting antivirals that can
      provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI)
      employs a photosensitizer, light, and oxygen to create a local burst of reactive
      oxygen species that inactivate microorganisms. The botanical plant extract
      OrthoquinTM is a powerful photosensitizer with antimicrobial properties. Here we
      report that Orthoquin also has antiviral properties. Photoactivated Orthoquin
      inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2
      (HSV-2) infection of target cells in a dose-dependent manner across a broad range
      of sub-cytotoxic concentrations. HSV inactivation required direct contact between
      Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect.
      Orthoquin did not cause appreciable damage to viral capsids or premature release
      of viral genomes, as measured by qPCR for the HSV-1 genome. By contrast,
      immunoblotting for HSV-1 antigens in purified virion preparations suggested that
      higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that
      altered protein mobility or antigen detection. Orthoquin PDI also inhibited the
      non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin
      mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light
      independent. Together, these findings suggest that the broad antiviral effects of
      Orthoquin-mediated PDI may stem from damage to viral attachment proteins.

PMID- 30274260
TI  - School Demands and Coping Resources-Associations with Multiple Measures of Stress
      in Mid-Adolescent Girls and Boys.
AB  - Stress, and stress-related health complaints, are common among young people,
      especially girls. Since studies have shown that school demands are an important
      driver of stress in adolescents, identifying if school-based resources can
      protect against stress is highly relevant. The aim of this study was to analyse
      task-related demands and task-related coping resources as aspects of the school
      work environment of potential relevance for stress in mid-adolescent girls and
      boys. The data came from "The School Stress and Support study" (TriSSS) conducted
      among students in grades 8 and 9 (aged 14-16 years). Self-reports of demands,
      coping resources, stress, as well as recurrent pain, were collected through
      questionnaires (n = 411). A subsample of students (n = 191-198) also provided
      salivary samples, which were analysed for the stress marker cortisol. Linear
      (OLS) and binary logistic regression analyses showed that higher demands were
      associated with more perceived stress, a higher likelihood of recurrent pain, and
      a lower cortisol awakening response. Greater coping resources were associated
      with less perceived stress and a lower likelihood of recurrent pain, but there
      was no association with cortisol. The strength of the associations differed by
      gender. The findings suggest that schools can promote student wellbeing by
      providing clear and timely information and teacher support to the students,
      especially for boys. Identifying specific features of the schoolwork that give
      rise to stress and to modify these accordingly is also of importance, especially
      for girls.

PMID- 30274261
TI  - Microwave-Assisted Extraction of Phenolic Compounds from Melastoma sanguineum
      Fruit: Optimization and Identification.
AB  - A microwave-assisted extraction (MAE) technology optimized by response surface
      methodology (RSM) was established to extract phenolic compounds from the fruit of
      Melastoma sanguineum. The effects of solvent composition, ratio of solvent to
      material, temperature, time and microwave power on phenol yield were evaluated in
      single-factor tests. The three parameters exerting main impacts on phenol yield
      were further optimized by RSM. Under optimal extraction conditions (31.33%
      ethanol, solvent/material ratio of 32.21 mL/g, 52.24  degrees C, 45 min and 500
      W), the total phenolic content was 39.02 +/- 0.73 mg gallic acid equivalent
      (GAE)/g dry weight (DW). This MAE method performed better in comparison with two
      conventional methods, those being maceration (25.79 +/- 1.03 mg GAE/g DW) and
      Soxhlet extraction (18.40 +/- 1.34 mg GAE/g DW), using lower process temperature,
      shorter irradiation time, and lower organic solvent consumption. In addition,
      five flavonoids (epicatechin gallate, epicatechin, rutin, pigallocatechin and
      quercetin) and two phenolic acids (protocatechuic acid and chlorogenic acid) in
      the extract were identified and quantified using UPLC-MS/MS.

PMID- 30274259
TI  - TIPE Family of Proteins and Its Implications in Different Chronic Diseases.
AB  - The tumor necrosis factor-alpha-induced protein 8-like (TIPE/TNFAIP8) family is a
      recently identified family of proteins that is strongly associated with the
      regulation of immunity and tumorigenesis. This family is comprised of four
      members, namely, tumor necrosis factor-alpha-induced protein 8 (TIPE/TNFAIP8),
      tumor necrosis factor-alpha-induced protein 8-like 1 (TIPE1/TNFAIP8L1), tumor
      necrosis factor-alpha-induced protein 8-like 2 (TIPE2/TNFAIP8L2), and tumor
      necrosis factor-alpha-induced protein 8-like 3 (TIPE3/TNFAIP8L3). Although the
      proteins of this family were initially described as regulators of tumorigenesis,
      inflammation, and cell death, they are also found to be involved in the
      regulation of autophagy and the transfer of lipid secondary messengers, besides
      contributing to immune function and homeostasis. Interestingly, despite the
      existence of a significant sequence homology among the four members of this
      family, they are involved in different biological activities and also exhibit
      remarkable variability of expression. Furthermore, this family of proteins is
      highly deregulated in different human cancers and various chronic diseases. This
      review summarizes the vivid role of the TIPE family of proteins and its
      association with various signaling cascades in diverse chronic diseases.

PMID- 30274262
TI  - METCAM/MUC18 Decreases the Malignant Propensity of Human Ovarian Carcinoma Cells.
AB  - METCAM/MUC18 is an integral membrane cell adhesion molecule (CAM) in the Ig-like
      gene super-family. It can carry out common functions of CAMs which is to perform
      intercellular interactions and interaction of cell with extracellular matrix in
      tumor microenvironment, to interact with various signaling pathways and to
      regulate general behaviors of cells. We and other two groups previously suggested
      that METCAM/MUC18 probably be utilized as a biomarker for predicting the
      malignant tendency of clinical ovarian carcinomas, since METAM/MUC18 expression
      appears to associate with the carcinoma at advanced stages. It has been further
      postulated to promote the malignant tendency of the carcinoma. However, our
      recent research results appear to support the conclusion that the above positive
      correlation is fortuitous; actually METCAM/MUC18 acts as a tumor and metastasis
      suppressor for the ovarian carcinoma cells. We also suggest possible mechanisms
      in the METCAM/MUC18-mediated early tumor development and metastasis of ovarian
      carcinoma. Moreover, we propose to employ recombinant METCAM/MUC18 proteins and
      other derived products as therapeutic agents to treat the ovarian cancer patients
      by decreasing the malignant potential of ovarian carcinoma.

PMID- 30274263
TI  - A Novel Naphthyridine Derivative, 3u, Induces Necroptosis at Low Concentrations
      and Apoptosis at High Concentrations in Human Melanoma A375 Cells.
AB  - Naphthyridine derivatives are a widely-used class of heterocycles due to their
      pharmacological activities. A novel compound (10-Methoxy-1,2,3,4
      tetrahydrobenzo(g)(1,3) diazepino(1,2-a)-(1,8)naphthyridin-6-yl)(phenyl)
      methanone (named 3u), showed good anticancer activity in the human malignant
      melanoma cell line A375 via Thiazolyl Blue Tetrazolium Bromide (MTT) assay. After
      Western blotting confirmed, we found that 3u induces necroptosis at low
      concentrations and apoptosis at high concentrations via the upregulation of death
      receptors and scaffold protein in A375 cells. Furthermore, by combining 3u with
      the caspase inhibitor zVAD-fmk or Receptor Interacting Serine/Threonine Kinase 1
      (RIP1) kinase inhibitor Necrostatin-1 (Nec-1), we found that the activity of
      caspase-8 was the crucial factor that determined whether either apoptosis or
      necroptosis occurred. The results indicate that 3u should be considered as a
      potential chemical substance for melanoma treatment.

PMID- 30274265
TI  - Effects of 3-Week Work-Matched High-Intensity Intermittent Cycling Training with
      Different Cadences on VO2max in University Athletes.
AB  - The aim of this study is to clarify the effects of 3-week work-matched high
      intensity intermittent cycling training (HIICT) with different cadences on the
      VO2max of university athletes. Eighteen university athletes performed HIICT with
      either 60 rpm (n = 9) or 120 rpm (n = 9). The HIICT consisted of eight sets of 20
      s exercise with a 10 s passive rest between each set. The initial training
      intensity was set at 135% of VO2max and was decreased by 5% every two sets.
      Athletes in both groups performed nine sessions of HIICT during a 3-week period.
      The total workload and achievement rate of the workload calculated before
      experiments in each group were used for analysis. VO2max was measured pre- and
      post-training. After 3 weeks of training, no significant differences in the total
      workload and the achievement rate of the workload were found between the two
      groups. VO2max similarly increased in both groups from pre- to post-training (p =
      0.016), with no significant differences between the groups (p = 0.680). These
      results suggest that cadence during HIICT is not a training variable affecting
      the effect of VO2max.

PMID- 30274266
TI  - A Joint Low-Power Cell Search and Frequency Tracking Scheme in NB-IoT Systems for
      Green Internet of Things.
AB  - As a dedicated communication protocol for Internet-of-Things, narrowband internet
      of things (NB-IoT) needs to establish the communication link rapidly and reduce
      retransmissions as much as possible to achieve low power consumption and stable
      performance. To achieve these targets, the low-power scheme of the initial cell
      search and frequency tracking is investigated in this paper. The cell search
      process can be subdivided into narrowband primary synchronization signal (NPSS)
      detection and narrowband secondary synchronization signal (NSSS) detection. We
      present an NPSS detection method whose timing metric is composed of symbol-wise
      autocorrelation and a dedicated normalization factor. After the detection of
      NPSS, the symbol timing and fractional frequency offset estimation is implemented
      in a resource-efficient way. NSSS detection is conducted in the frequency domain
      with a calculation-reduced algorithm based on the features of NSSS sequences. To
      compensate the accumulated frequency offset during uplink transmission, a pilot
      aided rapid frequency tracking algorithm is proposed. The simulation results of
      the proposed cell search scheme are outstanding in both normal coverage and
      extended coverage NB-IoT scenarios, and the accumulated frequency offset can be
      estimated with high efficiency.

PMID- 30274267
TI  - Analysis of DME/DME Navigation Performance and Ground Network Using Stretched
      Front-Leg Pulse-Based DME.
AB  - Global navigation satellite systems (GNSS) have become a primary navigation means
      for aircraft. However, the signal power of GNSS is very weak, and its service can
      be disrupted at any time when there is interference or jamming. For this reason,
      the Federal Aviation Administration (FAA) in the United States has recently
      chosen a distance measuring equipment (DME)-based aircraft navigation technique,
      called DME/DME, as an alternative aircraft navigation means for use by around
      2030. The reason that the FAA plans to use DME/DME in such a short duration, by
      around 2030, is presumed to be because the ranging accuracy of DMEs is between 70
      to 300 m, which is about 7 to 30 times worse than that of GNSS. Thus, a
      significant loss of positioning performance is unavoidable with current DMEs. To
      make DME/DME a more competent alternative positioning source, this paper proposes
      an advanced DME that could provide a ranging accuracy of around 30 m by employing
      a recently developed Stretched-Front-Leg (SFOL) pulse. The paper introduces
      optimal ground station augmentation algorithms that help to efficiently transform
      the current DME ground network to enable a DME/DME positioning accuracy of up to
      0.3 nm or 92.6 m with a minimal number of new ground DME sites. The positioning
      performance and augmented ground network using the proposed SFOL pulse-based DME
      are evaluated in two regions which have distinct terrain conditions.

PMID- 30274264
TI  - HCMV Infection and Apoptosis: How Do Monocytes Survive HCMV Infection?
AB  - Human cytomegalovirus (HCMV) infection of peripheral blood monocytes plays a key
      role in the hematogenous dissemination of the virus to multiple organ systems
      following primary infection or reactivation of latent virus in the bone marrow.
      Monocytes have a short life span of 1-3 days in circulation; thus, HCMV must
      alter their survival and differentiation to utilize these cells and their
      differentiated counterparts-macrophages-for dissemination and long term viral
      persistence. Because monocytes are not initially permissive for viral gene
      expression and replication, HCMV must control host-derived factors early during
      infection to prevent apoptosis or programmed cell death prior to viral induced
      differentiation into naturally long-lived macrophages. This review provides a
      short overview of HCMV infection of monocytes and describes how HCMV has evolved
      to utilize host cell anti-apoptotic pathways to allow infected monocytes to
      bridge the 48-72 h viability gate so that differentiation into a long term stable
      mature cell can occur. Because viral gene expression is delayed in monocytes
      following initial infection and only occurs (begins around two to three weeks
      post infection in our model) following what appears to be complete
      differentiation into mature macrophages or dendritic cells, or both; virally
      encoded anti-apoptotic gene products cannot initially control long term infected
      cell survival. Anti-apoptotic viral genes are discussed in the second section of
      this review and we argue they would play an important role in long term
      macrophage or dendritic cell survival following infection-induced
      differentiation.

PMID- 30274269
TI  - Association between eNOS Gene Polymorphism (T786C and VNTR) and Sickle Cell
      Disease Patients in Ghana.
AB  - Endothelial nitric oxide synthase (eNOS) variants have been found to be
      associated with several vascular disorders as well as the pathogenesis of sickle
      cell disease (SCD) complications such as vaso-occlusive crises (VOC). Studies on
      eNOS gene variants among SCD patients are rare in Ghana and several other African
      countries. The current study aimed to determine a possible association between
      variants of the eNOS gene (variable number of tandem repeats in intron 4 and
      T786C) in SCD complications among Ghanaian patients. This was a cross-sectional
      study involving 89 HbSS patients with complications and 46 HbSS patients without
      complications. Genomic DNA was extracted from leukocytes in the buffy coat and
      separated from collected whole blood samples of the study participants. PCR
      amplification, followed by restriction fragment length polymorphism (RFLP) was
      used to genotype T786C (rs2070744) variants. Variable number of tandem repeats
      (VNTR) in intron 4 was genotyped by PCR and direct electrophoresis. There was a
      significant difference in the genotype frequency of the T786C variant between
      HbSS patients with complications and those without complications (p = 0.0165).
      However, there was no significant difference in the VNTR intron 4 variant of the
      eNOS gene between patients with complications and those without complications (p
      > 0.05). The study shows an association between the eNOS gene variant (T786C) and
      complications in SCD.

PMID- 30274268
TI  - Assessment of the Public Health Threats Posed by Vector-Borne Disease in the
      United Kingdom (UK).
AB  - In recent years, the known distribution of vector-borne diseases in Europe has
      changed, with much new information also available now on the status of vectors in
      the United Kingdom (UK). For example, in 2016, the UK reported their first
      detection of the non-native mosquito Aedes albopictus, which is a known vector
      for dengue and chikungunya virus. In 2010, Culex modestus, a principal mosquito
      vector for West Nile virus was detected in large numbers in the Thames estuary.
      For tick-borne diseases, data on the changing distribution of the Lyme
      borreliosis tick vector, Ixodes ricinus, has recently been published, at a time
      when there has been an increase in the numbers of reported human cases of Lyme
      disease. This paper brings together the latest surveillance data and pertinent
      research on vector-borne disease in the UK, and its relevance to public health.
      It highlights the need for continued vector surveillance systems to monitor our
      native mosquito and tick fauna, as well as the need to expand surveillance for
      invasive species. It illustrates the importance of maintaining surveillance
      capacity that is sufficient to ensure accurate and timely disease risk assessment
      to help mitigate the UK's changing emerging infectious disease risks, especially
      in a time of climatic and environmental change and increasing global
      connectivity.

PMID- 30274271
TI  - Impact of Age-Adjusted Charlson Comorbidity on Hospital Survival and Short-Term
      Outcome of Patients with Extracorporeal Cardiopulmonary Resuscitation.
AB  - Extracorporeal cardiopulmonary resuscitation (ECPR) has gradually come to be
      regarded as an effective therapy, but the hospital mortality rate after ECPR is
      still high and unpredictable. The present study tested whether age-adjusted
      Charlson comorbidity index (ACCI) can be used as an objective selection criterion
      to ensure the most efficient utilization of medical resources. Adult patients
      (age >= 18 years) receiving ECPR at our institution between 2006 and 2015 were
      included. Data regarding ECPR events and ACCI characteristics were collected
      immediately after the extracorporeal membrane oxygenation (ECMO) setup. Adverse
      events during hospitalization were also prospectively collected. The primary
      endpoint was survival to hospital discharge. The second endpoint was the short
      term (2-year) follow-up outcome. A total of 461 patients included in the study
      were grouped into low ACCI (ACCI 0-3) (240, 52.1%) and high ACCI (ACCI 4-13)
      (221, 47.9%) groups. The median ACCI was 2 (interquartile range (IQR): 1-3) and 5
      (IQR: 4-7) for the low and high ACCI groups, respectively. Cardiopulmonary
      resuscitation (CPR)-to-ECMO duration was comparable between the groups (42.1 +/-
      25.6 and 41.3 +/- 20.7 min in the low and high ACCI groups, respectively; p =
      0.754). Regarding the hospital survival rate, 256 patients (55.5%) died on ECMO
      support. A total of 205 patients (44.5%) were successfully weaned off ECMO, but
      only 138 patients (29.9%) survived to hospital discharge (32.1% and 27.6% in low
      and high ACCI group, p = 0.291). Multivariate logistic regression analysis
      revealed CPR duration before ECMO run (CPR-to-ECMO duration) and a CPR cause of
      septic shock to be significant risk factors for hospital survival after ECPR (p =
      0.043 and 0.014, respectively), whereas age and ACCI were not (p = 0.334 and
      0.164, respectively). The 2-year survival rate after hospital discharge for the
      138 hospital survivors was 96% and 74% in the low and high ACCI groups,
      respectively (p = 0.002). High ACCI before ECPR does not predict a poor outcome
      of hospital survival. Therefore, ECPR should not be rejected solely due to high
      ACCI. However, high ACCI in hospital survivors is associated with a higher 2-year
      mortality rate than low ACCI, and patients with high ACCI should be closely
      followed up.

PMID- 30274270
TI  - Neighborhood Violence Impacts Disease Control and Surveillance: Case Study of
      Cali, Colombia from 2014 to 2016.
AB  - Arboviruses are responsible for a large burden of disease globally and are thus
      subject to intense epidemiological scrutiny. However, a variable notably absent
      from most epidemiological analyses has been the impact of violence on arboviral
      transmission and surveillance. Violence impedes surveillance and delivery of
      health and preventative services and affects an individual's health-related
      behaviors when survival takes priority. Moreover, low and middle-income countries
      bear a disproportionately high burden of violence and related health outcomes,
      including vector borne diseases. To better understand the epidemiology of
      arboviral outbreaks in Cali, Colombia, we georeferenced chikungunya (CHIKV),
      dengue (DENV), and Zika (ZIKV) viral cases from The National System of
      Surveillance in Public Health between October 2014 and April 2016. We extracted
      homicide data from the municipal monthly reports and kernel density of homicide
      distribution from IdeasPaz. Crucially, an overall higher risk of homicide is
      associated with increased risk of reported DENV, lower rates of acute testing,
      and higher rates of lab versus clinical discordance. In the context of high
      violence as a potential barrier to access to preventive health services, a
      community approach to improve health and peace should be considered.

PMID- 30274272
TI  - Impact of Different Estimation Methods on Obesity-Attributable Mortality Levels
      and Trends: The Case of The Netherlands.
AB  - The available methodologies to estimate the obesity-attributable mortality
      fraction (OAMF) affect the levels found and hamper the construction of time
      series. Our aim was to assess the impact of using different techniques to
      estimate the levels and the trends in obesity-attributable mortality for The
      Netherlands between 1981 to 2013. Using Body Mass Index (BMI), all-cause and
      cause-specific mortality data, and worldwide and European relative risks (RRs),
      we estimated OAMFs using three all-cause approaches (partially adjusted, weighted
      sum, and the two combined) and one cause-of-death approach (Comparative Risk
      Assessment; CRA). We adjusted the CRA approach to purely capture obesity (BMI >=
      30 kg/m2). The different approaches led to a range of estimates. The weighted sum
      method using worldwide RRs generated the lowest (0.9%) while the adjusted CRA
      approach using 2013 RRs generated the highest estimate (1.5%). Using European
      specific RRs instead of worldwide RRs resulted in higher estimates. Most of the
      approaches revealed an increasing OAMF over the period 1981 to 2013 especially
      from 1993 onwards except for the adjusted CRA approach among women. Estimates of
      OAMF levels and trends differed depending on the method applied. Given the
      limited available data, we recommend using the weighted-sum method to compare
      obesity-attributable mortality across European countries over time.

PMID- 30274273
TI  - Activation of a Raw Clay by Mechanochemical Process-Effects of Various Parameters
      on the Process Efficiency and Cementitious Properties.
AB  - The efficiency of the mechanochemical activation (MCA) is influenced by various
      process parameters as well as by the properties of the treated material. The main
      objective of this research was to optimize the MCA process, gaining enhancement
      of the chemical reactivity of a Swedish raw clay, which is going to be used as an
      alkali-activated cementitious binder. The effects of the amount of water, the
      filling ratio, the rotation speed, and the grinding duration on the amorphization
      degree were evaluated by X-Ray Diffraction (XRD) and Scanning Electron Microscopy
      (SEM). Generally, wet and dry processes showed an extensive amorphization of both
      kaolinite and muscovite minerals present in the studied clay. On the contrary,
      quartz was amorphized mainly by the wet grinding process. The efficiency of both
      dry and wet grinding processes was enhanced by the increased number of grinding
      media versus the amount of the activated material. However, longer processing
      times caused significant agglomeration while a higher rotational speed enhanced
      the amorphization. Preliminary tests have shown that alkali activation of the
      processed clays produced hardened samples. Furthermore, the increased
      amorphization corresponded to the increased compressive strength values.

PMID- 30274275
TI  - A Rationale for Mesoscopic Domain Formation in Biomembranes.
AB  - Cell plasma membranes display a dramatically rich structural complexity
      characterized by functional sub-wavelength domains with specific lipid and
      protein composition. Under favorable experimental conditions, patterned
      morphologies can also be observed in vitro on model systems such as supported
      membranes or lipid vesicles. Lipid mixtures separating in liquid-ordered and
      liquid-disordered phases below a demixing temperature play a pivotal role in this
      context. Protein-protein and protein-lipid interactions also contribute to
      membrane shaping by promoting small domains or clusters. Such phase separations
      displaying characteristic length-scales falling in-between the nanoscopic,
      molecular scale on the one hand and the macroscopic scale on the other hand, are
      named mesophases in soft condensed matter physics. In this review, we propose a
      classification of the diverse mechanisms leading to mesophase separation in
      biomembranes. We distinguish between mechanisms relying upon equilibrium
      thermodynamics and those involving out-of-equilibrium mechanisms, notably active
      membrane recycling. In equilibrium, we especially focus on the many mechanisms
      that dwell on an up-down symmetry breaking between the upper and lower bilayer
      leaflets. Symmetry breaking is an ubiquitous mechanism in condensed matter
      physics at the heart of several important phenomena. In the present case, it can
      be either spontaneous (domain buckling) or explicit, i.e., due to an external
      cause (global or local vesicle bending properties). Whenever possible,
      theoretical predictions and simulation results are confronted to experiments on
      model systems or living cells, which enables us to identify the most realistic
      mechanisms from a biological perspective.

PMID- 30274274
TI  - Antibiotics from Deep-Sea Microorganisms: Current Discoveries and Perspectives.
AB  - The increasing emergence of new forms of multidrug resistance among human
      pathogenic bacteria, coupled with the consequent increase of infectious diseases,
      urgently requires the discovery and development of novel antimicrobial drugs with
      new modes of action. Most of the antibiotics currently available on the market
      were obtained from terrestrial organisms or derived semisynthetically from
      fermentation products. The isolation of microorganisms from previously unexplored
      habitats may lead to the discovery of lead structures with antibiotic activity.
      The deep-sea environment is a unique habitat, and deep-sea microorganisms,
      because of their adaptation to this extreme environment, have the potential to
      produce novel secondary metabolites with potent biological activities. This
      review covers novel antibiotics isolated from deep-sea microorganisms. The
      chemical classes of the compounds, their bioactivities, and the sources of
      organisms are outlined. Furthermore, the authors report recent advances in
      techniques and strategies for the exploitation of deep-sea microorganisms.

PMID- 30274276
TI  - A Passive Tracking System Based on Geometric Constraints in Adaptive Wireless
      Sensor Networks.
AB  - Target tracking technologies in wireless sensor network (WSNs) environments fall
      into two categories: active and passive schemes. Unlike with the active
      positioning schemes, in which the targets are required to hold cooperative
      devices, the research on passive tracking, i.e., tracking device-free targets,
      has recently showed promise. In the WSN, device-free targets can be tracked by
      sensing radio frequency tomography (RFT) on the line-of-sight links (LOSLs). In
      this paper, we propose a passive tracking scheme exploiting both adaptive
      networking LOSL webs and geometric constraint methodology for tracking single
      targets, as well as multiple targets. Regarding fundamental knowledge, we firstly
      explore the spatial diversity technique for RFT detection in realistic
      situations. Then, we analyze the power consumption of the WSN and propose an
      adaptive networking scheme for the purpose of energy conservation. Instead of
      maintaining a fixed LOSL density, the proposed scheme can adaptively adjust the
      networking level to save energy while guaranteeing tracking accuracy. The
      effectiveness of the proposed scheme is evaluated with computer simulations.
      According to the results, it is observed that the proposed scheme can
      sufficiently reduce power consumption, while providing qualified tracking
      performance.

PMID- 30274278
TI  - A New Bias Error Prediction Model for High-Precision Transfer Alignment.
AB  - The purpose of this work was to study bias error in acceleration-based transfer
      alignment, which is probably caused by cross-correlation between the dynamic
      lever-arm and the linear motion of a ship. A new prediction model for the cross
      correlation-caused error is proposed in this paper. We adopt the Bernoulli-Euler
      Beam as a simplified ship hull-girder model to verify the existence of the cross
      correlation. Then, the mathematical mechanism and the prediction model of the
      bias error are deduced via the ordinary least squares theory. Three factors
      influence the bias error in the prediction model: the amplitude of the dynamic
      lever arm acceleration, the amplitude of the ship motion acceleration, and the
      cross-correlation between them. Simulation experiments are then conducted to test
      the influence of the factors. The results show that the mechanism analysis is
      reasonable, and the bias error prediction model is in agreement with the
      experimental results. Thus, the proposed prediction model has the potential to
      deduce the bias error in high-accuracy transfer alignment.

PMID- 30274277
TI  - Topical Delivery of Senicapoc Nanoliposomal Formulation for Ocular Surface
      Treatments.
AB  - Topical ophthalmologic treatments have been facing great challenges with main
      limitations of low drug bioavailability, due to highly integrative defense
      mechanisms of the eye. This study rationally devised strategies to increase drug
      bioavailability by increasing ocular surface residence time of drug-loaded
      nanoliposomes dispersed within thermo-sensitive hydrogels (Pluronic F-127).
      Alternatively, we utilized sub-conjunctival injections as a depot technique to
      localize nanoliposomes. Senicapoc was encapsulated and sustainably released from
      free nanoliposomes and hydrogels formulations in vitro. Residence time increased
      up to 12-fold (60 min) with 24% hydrogel formulations, as compared to 5 min for
      free liposomes, which was observed in the eyes of Sprague-Dawley rats using
      fluorescence measurements. Pharmacokinetic results obtained from flushed tears,
      also showed that the hydrogels had greater drug retention capabilities to that of
      topical viscous solutions for up to 60 min. Senicapoc also remained quantifiable
      within sub-conjunctival tissues for up to 24 h post-injection.

PMID- 30274279
TI  - Inhibition of TRPV1 Channel Activity in Human CD4+ T Cells by Nanodiamond and
      Nanoplatinum Liquid, DPV576.
AB  - Background: Transient receptor potential vanilloid (TRPV) channels act as sensors
      of pain, temperature, and other external stimuli. We have recently shown that
      DPV576, an aqueous mixture of nanodiamond (ND) and nanoplatinum (NP), can
      modulate the activity of TRPV on human primary keratinocytes, suggesting their
      potential as a possible pain modulator. Here, we sought to examine the effect of
      DPV576 in modulating the functions of human CD4+ T lymphocytes and whether the
      modulation is mediated via TRPV channels. Materials and methods: Human primary
      CD4+ T cells were activated with anti CD3/CD28 with and without DPV576 at 1:10
      and 1:100 dilutions for 24 h in vitro. TRPV receptor expression (TRPV1 and TRPV4)
      on CD4+ T cells were examined by flow cytometry. The capacity of DPV576 to
      modulate the activity of TRPV1 agonist capsaicin in CD4+ T cells was also
      determined. Activation of CD4+ T cells was determined by production of cytokines
      TNF-alpha, IFN-gamma, and IL-10 using specific ELISA kits. Results: DPV576
      treatment of CD4+ T cells that were activated with anti CD3/CD28 resulted in
      decreased expression of the TRPV1 channel, but had no effect on TRPV4. This was
      accompanied by decreased secretion of IFN-gamma and reduced expression of TRPV1
      in capsaicin activated CD4+ T cells. In addition, DPV576 inhibited the capsaicin,
      induced the production of IFN-gamma, and enhanced the secretion of IL-10.
      Conclusion: We conclude that short term exposure to DPV576 inhibits the activity
      of TRPV1 channels in CD4+ T lymphocytes, which may suggest its possible
      beneficial use for pain management.

PMID- 30274281
TI  - Incorporation of PVDF Nanofibre Multilayers into Functional Structure for
      Filtration Applications.
AB  - Membranes are considered as a promising technology for separation and filtration
      processes. Here, novel polyvinylidene fluoride (PVDF) nanofibrous multilayer
      membranes were fabricated by wire-based industrial electrospinning equipment
      following by a lamination process. The lamination process was optimised under
      various applied temperature, force of lamination, and lamination time. Air
      permeability and burst-pressure tests were run to determine the optimum membranes
      for filtration application. The structures of the prepared membranes were
      characterised by scanning electron microscopy and pore-size analysis. The
      hydrophilic properties of the membranes were evaluated using water contact angle
      measurement, and the mechanical strength of the membranes was analysed. Air and
      water filtration tests were run to find the possible application of prepared
      membranes. The air filtration results showed that membranes had high filtration
      efficiencies: Over 99.00% for PM2.5, and PM0.1. The water filtration results
      indicated that permeability of the membranes changed from 288 to 3275 L/m2hbar.
      The successful preparation of such an interesting material may provide a new
      approach for the design and development of electrospun filter membranes.

PMID- 30274280
TI  - Bipolar Tumor-Associated Macrophages in Ovarian Cancer as Targets for Therapy.
AB  - Ovarian cancer, a rare but fatal disease, has been a challenging area in the
      field of gynecological cancer. Ovarian cancer is characterized by peritoneal
      metastasis, which is facilitated by a cross-talk between tumor cells and other
      cells in the tumor microenvironment (TME). In epithelial ovarian cancer, tumor
      associated macrophages (TAMs) constitute over 50% of cells in the peritoneal TME
      and malignant ascites, and are potential targets for therapy. Here, we review the
      bipolar nature of TAMs and the evolving strategies to target TAMs in ovarian
      cancer.

PMID- 30274283
TI  - Overview of Phase-Change Electrical Probe Memory.
AB  - Phase-change electrical probe memory has recently attained considerable attention
      owing to its profound potential for next-generation mass and archival storage
      devices. To encourage more talented researchers to enter this field and thereby
      advance this technology, this paper first introduces approaches to induce the
      phase transformation of chalcogenide alloy by probe tip, considered as the root
      of phase-change electrical probe memory. Subsequently the design rule of an
      optimized architecture of phase-change electrical probe memory is proposed based
      on a previously developed electrothermal and phase kinetic model, followed by a
      summary of the state-of-the-art phase-change electrical probe memory and an
      outlook for its future prospects.

PMID- 30274282
TI  - The Effects of Carbon Content on the Anisotropic Deformation Mechanism of Boron
      Carbide.
AB  - The effects of carbon content on the mechanical properties and deformation
      mechanisms of boron carbides were investigated by first-principles calculations,
      based on the density functional theory. The B12-CBC (13.33 at % C) and B10 C 2 P 
      CC (28.75 at % C) were studied and then compared with the deformation of regular
      B11CP-CBC (20.0 at % C). The results show the B10 C 2 P -CC, which has the lowest
      carbon content, has the highest strength and hardness as well as the lowest
      toughness. With the increase of carbon content, the rhombohedral symmetry will be
      broken and the three-atoms chains will be replaced by diatomic carbon chains.
      These changes may have an influence on their anisotropic deformation mechanisms.
      For the B12-CBC, the destruction of icosahedra without bending three-atom chains
      causes structural failure for compression along the c axis; while for compression
      along the a axis, new B-B bonds are formed, causing an unrecoverable deformation;
      then it is gradually destroyed until full destruction. For the B10 C 2 P -CC, the
      anisotropic deformation mechanism is not obvious. For both loading directions,
      the breakage of B-CP bonds causes the stress to drop, suggesting that the
      structure is beginning to be destroyed. Finally, the icosahedra are fully
      destroyed, resulting in structural failure.

PMID- 30274284
TI  - Calibrating the Severity of Forest Defoliation by Pine Processionary Moth with
      Landsat and UAV Imagery.
AB  - The pine processionary moth (Thaumetopoea pityocampa Dennis and Schiff.), one of
      the major defoliating insects in Mediterranean forests, has become an increasing
      threat to the forest health of the region over the past two decades. After a
      recent outbreak of T. pityocampa in Catalonia, Spain, we attempted to estimate
      the damage severity by capturing the maximum defoliation period over winter
      between pre-outbreak and post-outbreak images. The difference in vegetation index
      (dVI) derived from Landsat 8 was used as the change detection indicator and was
      further calibrated with Unmanned Aerial Vehicle (UAV) imagery. Regression models
      between predicted dVIs and observed defoliation degrees by UAV were compared
      among five selected dVIs for the coefficient of determination. Our results found
      the highest R-squared value (0.815) using Moisture Stress Index (MSI), with an
      overall accuracy of 72%, as a promising approach for estimating the severity of
      defoliation in affected areas where ground-truth data is limited. We concluded
      with the high potential of using UAVs as an alternative method to obtain ground
      truth data for cost-effectively monitoring forest health. In future studies,
      combining UAV images with satellite data may be considered to validate model
      predictions of the forest condition for developing ecosystem service tools.

PMID- 30274285
TI  - Visualization of Tau-Tubulin Interaction in a Living Cell Using Bifluorescence
      Complementation Technique.
AB  - Tau is a neuron-specific microtubule-binding protein that stabilizes
      microtubules. It is generally thought that highly phosphorylated tau dissociates
      from microtubules and becomes insoluble aggregates, leading to neuronal
      degeneration. Due to the implication of tau aggregation in neurodegenerative
      disorders, including Alzheimer's disease, great efforts have been made to
      identify the tau aggregation process. However, tau interaction with tubulin
      during the aggregation process remains largely unknown. To scrutinize the tau
      tubulin interaction, we generated a cell model that enables visualization of the
      tau-tubulin interaction in a living cell using the Bifluorescence Complementation
      (BiFC) Technique. Upon diverse chemical stimulation that induced tau pathology,
      tau-tubulin BiFC cells showed significantly increased levels of BiFC
      fluorescence, indicating that tau aggregates together with tubulin. Our results
      suggest that tubulin should be considered as a key component in the tau
      aggregation process.

PMID- 30274286
TI  - An Underwater Time Reversal Communication Method Using Symbol-Based Doppler
      Compensation with a Single Sound Pressure Sensor.
AB  - Due to the significant multipath and Doppler effects in the underwater acoustic
      (UWA) channel, the quality of the received signal is degraded, which seriously
      affects the performance of UWA communication. The paper proposes a time reversal
      UWA communication method combined with a symbol-based Doppler compensation (SBDC)
      technique to solve those problems. A single element time reversal mirror (TRM) is
      used to realize channel equalization and mitigate the inter-symbol interference
      (ISI) resulting from multipath propagation. The SBDC technique is subsequently
      used to compensate Doppler effects in the received signal, thereby reducing the
      bit error rate (BER) and improving the communication performance. In order to
      verify the performance of the proposed communication method, some simulations
      with real sounding channels were performed. Moreover, a field UWA communication
      experiment was conducted in the Songhua River (Harbin, China). The UWA
      communication experiment achieves nearly error-free performance with a
      communication rate of 100 bit/s in the bandwidth of 2 kHz. The results of the
      experiment demonstrate the feasibility and robustness of the proposed UWA
      communication method.

PMID- 30274287
TI  - Neuromodulation for Pelvic and Urogenital Pain.
AB  - Chronic pain affecting the pelvic and urogenital area is a major clinical problem
      with heterogeneous etiology, affecting both male and female patients and severely
      compromising quality of life. In cases where pharmacotherapy is ineffective,
      neuromodulation is proving to be a potential avenue to enhance analgesic
      outcomes. However, clinicians who frequently see patients with pelvic pain are
      not traditionally trained in a range of neuromodulation techniques. The aim of
      this overview is to describe major types of pelvic and urogenital pain syndromes
      and the neuromodulation approaches that have been trialed, including peripheral
      nerve stimulation, dorsal root ganglion stimulation, spinal cord stimulation, and
      brain stimulation techniques. Our conclusion is that neuromodulation,
      particularly of the peripheral nerves, may provide benefits for patients with
      pelvic pain. However, larger prospective randomized studies with carefully
      selected patient groups are required to establish efficacy and determine which
      patients are likely to achieve the best outcomes.

PMID- 30274288
TI  - Pharmacokinetic and Metabolism Studies of 12-Riboside-Pseudoginsengenin DQ by
      UPLC-MS/MS and UPLC-QTOF-MSE.
AB  - Pharmacokinetic and metabolism studies of 12-riboside-pseudoginsengenin DQ
      (RPDQ), a novel ginsenoside with an anti-cancer effect, were carried out, aiming
      at discussing the characteristics of the ginsenoside with glycosylation site at C
      12. In the pharmacokinetic analysis, we developed and validated a method by UPLC
      MS to quantify RPDQ in rat plasma. In the range of 5-1000 ng/mL, the assay was
      linear (R2 > 0.9966), with the LLOQ (lower limit of quantification) being 5
      ng/mL. The LOD (limit of detection) was 1.5 ng/mL. The deviations of intra-day
      and inter-day, expressed as relative standard deviation (RSD), were <= 3.51% and
      <= 5.41% respectively. The accuracy, expressed as relative error (RE), was in the
      range -8.82~3.47% and -5.61~2.87%, respectively. The recoveries were in the range
      85.66~92.90%. The method was then applied to a pharmacokinetic study in rats
      intragastrically administrated with 6, 12, and 24 mg/kg RPDQ. The results showed
      that RPDQ exhibited slow oral absorption (Tmax = 7.0 h, 7.5 h, and 7.0 h,
      respectively), low elimination (t1/2 = 12.59 h, 12.83 h, and 13.74 h,
      respectively) and poor absolute bioavailability (5.55, 5.15, and 6.08%,
      respectively). Moreover, the investigation of metabolites were carried out by
      UPLC-QTOF-MS. Thirteen metabolites of RPDQ were characterized from plasma, bile,
      urine, and feces of rats. Some metabolic pathways, including oxidation,
      acetylation, hydration, reduction, hydroxylation, glycine conjugation, sulfation,
      phosphorylation, glucuronidation, glutathione conjugation, and deglycosylation,
      were profiled. In general, both the rapid quantitative method and a good
      understanding of the characteristics of RPDQ in vivo were provided in this study.

PMID- 30274289
TI  - Solid-Phase Extraction of Polar Benzotriazoles as Environmental Pollutants: A
      Review.
AB  - Polar benzotriazoles are corrosion inhibitors with widespread use; they are
      environmentally characterized as emerging pollutants in the water system, where
      they are present in low concentrations. Various extraction methods have been used
      for their separation from various matrices, ranging from classical liquid-liquid
      extractions to various microextraction techniques, but the most frequently
      applied extraction technique remains the solid-phase extraction (SPE), which is
      the focus of this review. We present an overview of the methods, developed in the
      last decade, applied for the determination of benzotriazoles in aqueous and solid
      environmental samples. Several other matrices, such as human urine and plant
      material, are also considered in the text. The methods are reviewed according to
      the determined compounds, sample matrices, cartridges and eluents used,
      extraction recoveries and the achieved limits of quantification. A critical
      evaluation of the advantages and drawbacks of the published methods is given.

PMID- 30274290
TI  - Representation of the QM Subsystem for Long-Range Electrostatic Interaction in
      Non-Periodic Ab Initio QM/MM Calculations.
AB  - In QM/MM calculations, it is essential to handle electrostatic interactions
      between the QM and MM subsystems accurately and efficiently. To achieve maximal
      efficiency, it is convenient to adopt a hybrid scheme, where the QM electron
      density is used explicitly in the evaluation of short-range QM/MM electrostatic
      interactions, while a multipolar representation for the QM electron density is
      employed to account for the long-range QM/MM electrostatic interactions. In order
      to avoid energy discontinuity at the cutoffs, which separate the short- and long
      range QM/MM electrostatic interactions, a switching function should be utilized
      to ensure a smooth potential energy surface. In this study, we benchmarked the
      accuracy of such hybrid embedding schemes for QM/MM electrostatic interactions
      using different multipolar representations, switching functions and cutoff
      distances. For test systems (neutral and anionic oxyluciferin in MM (aqueous and
      enzyme) environments), the best accuracy was acquired with a combination of QM
      electrostatic potential (ESP) charges and dipoles and two switching functions
      (long-range electrostatic corrections (LREC) and Switch) in the treatment of long
      range QM/MM electrostatics. It allowed us to apply a 10A distance cutoff and
      still obtain QM/MM electrostatics/polarization energies within 0.1 kcal/mol and
      time-dependent density functional theory (TDDFT)/MM vertical excitation energies
      within 10-3 eV from theoretical reference values.

PMID- 30274291
TI  - Chemical Composition of Myrtle (Myrtus communis L.) Berries Essential Oils as
      Observed in a Collection of Genotypes.
AB  - Myrtle (Myrtus communis L.) is a shrub spontaneously growing in the Mediterranean
      area. The leaf and fruit content of essential oils and phenolic compounds justify
      the wide use of the plant as medicinal and aromatic. Because of overexploitation
      of wild plants, a domestication process is in progress in different regions and
      the influence of the genotype variability on the chemical composition of fruit
      essential oils may be useful to breeding programs. Consequently, the analysis
      performed on a selected group of candidate clones growing in the same field
      collection in Sardinia is the object of this report. Forty-seven selections
      provided fully ripe fruits for essential oil extraction by hydrodistillation and
      Gas Chromatography-Mass Spectrometry (GC-MS) analysis. Only five candidate clones
      showed white fruits. The highest yield of essential oil was observed in the LAC31
      genotype with 0.55 g.kg-1, while the samples BOS1, MON5, RUM4, RUM10, V4 and V8
      showed values above 0.20 g.kg-1 and most of the genotypes under 0.10 g.kg-1.
      Geranyl acetate was the compound with the highest relative abundance. The second
      compound for relative abundance was the 1,8-cineole. Other compounds with high
      relative abundance were alpha-terpinyl acetate, methyleugenol, linalool, alpha
      terpineol, beta-caryophyllene, alpha-humulene, Trans-caryophyllene oxide, and
      humulene epoxide II.

PMID- 30274292
TI  - Investigation of the Effects of Purpose in Life, Grit, Gratitude, and School
      Belonging on Mental Distress among Chinese Emerging Adults.
AB  - Given the high prevalence of mental distress indicators, such as depression,
      among emerging adults, it is imperative to identify not only factors that place
      them at risk for mental distress, but also those that protect against it. This
      study tested the direct and indirect effects (via purpose in life) of gratitude,
      two aspects of grit (i.e., consistency of interest and perseverance of effort),
      and school belonging on three indicators of mental distress (i.e., depression,
      anxiety, and stress). A total of 468 Chinese university students (58.3% female),
      aged 18 to 27, in Macao, China responded to an anonymous questionnaire between
      April to May, 2016. As expected, all psychosocial factors were negatively
      associated with all three indicators of mental distress (r = -0.15 to -0.42, p <
      0.05), with the exception of perseverance of effort, which had a significant,
      negative association with depression only. The results of path analysis showed
      that purpose in life significantly mediated the effect of school belonging and
      perseverance of effort on depression, whereas school belonging, gratitude, and
      consistency of interest all had direct effects on all three indicators of mental
      distress (p < 0.05). Our results also suggested that the two components of grit
      may have differential effects on mental distress among Chinese emerging adults.
      School-based programs should consider positive psychology interventions in
      Chinese populations.

PMID- 30274293
TI  - A Metabolomic-Based Evaluation of the Role of Commensal Microbiota throughout the
      Gastrointestinal Tract in Mice.
AB  - Commensal microbiota colonize the surface of our bodies. The inside of the
      gastrointestinal tract is one such surface that provides a habitat for them. The
      gastrointestinal tract is a long organ system comprising of various parts, and
      each part possesses various functions. It has been reported that the composition
      of intestinal luminal metabolites between the small and large intestine are
      different; however, comprehensive metabolomic and commensal microbiota profiles
      specific to each part of the gastrointestinal lumen remain obscure. In this
      study, by using capillary electrophoresis time-of-flight mass spectrometry (CE
      TOFMS)-based metabolome and 16S rRNA gene-based microbiome analyses of specific
      pathogen-free (SPF) and germ-free (GF) murine gastrointestinal luminal profiles,
      we observed the different roles of commensal microbiota in each part of the
      gastrointestinal tract involved in carbohydrate metabolism and nutrient
      production. We found that the concentrations of most amino acids in the SPF small
      intestine were higher than those in the GF small intestine. Furthermore, sugar
      alcohols such as mannitol and sorbitol accumulated only in the GF large
      intestine, but not in the SPF large intestine. On the other hand, pentoses, such
      as arabinose and xylose, gradually accumulated from the cecum to the colon only
      in SPF mice, but were undetected in GF mice. Correlation network analysis between
      the gastrointestinal microbes and metabolites showed that niacin metabolism might
      be correlated to Methylobacteriaceae. Collectively, commensal microbiota
      partially affects the gastrointestinal luminal metabolite composition based on
      their metabolic dynamics, in cooperation with host digestion and absorption.

PMID- 30274295
TI  - Paths for Improving Bevacizumab Available in 2018: The ADZT Regimen for Better
      Glioblastoma Treatment.
AB  - During glioblastoma treatment, the pharmaceutical monoclonal antibody to vascular
      endothelial growth factor A, bevacizumab, has improved the quality of life and
      delayed progression for several months, but has not (or only marginally)
      prolonged overall survival. In 2017, several dramatic research papers appeared
      that are crucial to our understanding of glioblastoma vis-a-vis the mode of
      action of bevacizumab. As a consequence of these papers, a new, potentially more
      effective treatment protocol can be built around bevacizumab. This is the ADZT
      regimen, where four old drugs are added to bevacizumab. These four drugs are
      apremilast, marketed to treat psoriasis, dapsone, marketed to treat Hansen's
      disease, zonisamide, marketed to treat seizures, and telmisartan, marketed to
      treat hypertension. The ancillary attributes of each of these drugs have been
      shown to augment bevacizumab. This paper details the research data supporting
      this contention. Phase three testing of AZDT addition to bevacizumab is required
      to establish safety and effectiveness before general use.

PMID- 30274294
TI  - Overexpression of PeHKT1;1 Improves Salt Tolerance in Populus.
AB  - Soil salinization is an increasingly serious threat that limits plant growth and
      development. Class I transporters of the high-affinity K+ transporter (HKT)
      family have been demonstrated to be involved in salt tolerance by contributing to
      Na+ exclusion from roots and shoots. Here, we isolated the PeHKT1;1 gene from
      hybrid poplar based on the sequences of the Populus trichocarpa genome. The full
      length PeHKT1;1 gene was 2173 bp, including a 1608 bp open reading frame (ORF)
      encoding 535 amino acids and containing eight distinct transmembrane domains.
      Multiple sequence alignment and phylogenetic analysis suggested that the PeHKT1;1
      protein had a typical S-G-G-G signature for the P-loop domains and belonged to
      class I of HKT transporters. PeHKT1;1 transcripts were mainly detected in stem
      and root, and were remarkably induced by salt stress treatment. In further
      characterization of its functions, overexpression of PeHKT1;1 in Populus
      davidiana * Populus bolleana resulted in a better relative growth rate in
      phenotypic analysis, including root and plant height, and exhibited higher
      catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) activities than
      non-transgenic poplar under salt stress conditions. These observations indicated
      that PeHKT1;1 may enhance salt tolerance by improving the efficiency of
      antioxidant systems. Together, these data suggest that PeHKT1;1 plays an
      important role in response to salt stress in Populus.

PMID- 30274297
TI  - Impact of CMOS Pixel and Electronic Circuitry in the Performance of a Hartmann
      Shack Wavefront Sensor.
AB  - This work presents a numerical simulation of a Hartmann-Shack wavefront sensor
      (WFS) that assesses the impact of integrated electronic circuitry on the sensor
      performance, by evaluating a full detection chain encompassing wavefront
      sampling, photodetection, electronic circuitry and wavefront reconstruction. This
      platform links dedicated C algorithms for WFS to a SPICE circuit simulator for
      integrated electronics. The complete codes can be easily replaced in order to
      represent different detection or reconstruction methods, while the circuit
      simulator employs reliable models of either off-the-shelf circuit components or
      custom integrated circuit modules. The most relevant role of this platform is to
      enable the evaluation of the applicability and constraints of the focal plane of
      a given wavefront sensor prior to the actual fabrication of the detector chip. In
      this paper, we will present the simulation results for a Hartmann-Shack wavefront
      sensor with an orthogonal array of quad-cells (QC) integrated along with active
      pixel (active-pixel sensor (APS)) circuitry and analog-to-digital converters
      (ADC) on a "complementary metal oxide semiconductor" (CMOS) process and deploying
      a modal wavefront reconstructor. This extended simulation capability for
      wavefront sensors enables the test and verification of different photosensitive
      and circuitry topologies for position-sensitive detectors combined with the
      simulation of sampling microlenses and reconstruction algorithms, with the goal
      of enhancing the accuracy in the prediction of the wavefront-sensor performance
      before a detector CMOS chip is actually fabricated.

PMID- 30274296
TI  - A Multifunctional Molecular Probe for Detecting Hg2+ and Ag+ Based on Ion
      Mediated Base Mismatch.
AB  - In this paper, a multifunctional biosensing platform for sensitively detecting
      Hg2+ and Ag+, based on ion-mediated base mismatch, fluorescent labeling, and
      strand displacement, is introduced. The sensor can also be used as an OR logic
      gate, the multifunctional design of sensors is realized. Firstly, orthogonal
      experiments with three factors and three levels were carried out on the designed
      sensor, and preliminary optimization of conditions was performed for subsequent
      experiments. Next, the designed sensor was tested the specificity and target
      selectivity under the optimized conditions, and the application to actual
      environmental samples further verified the feasibility. Generally, this is a
      convenient, fast, stable, and low-cost method that provides a variety of ideas
      and an experimental basis for subsequent research.

PMID- 30274299
TI  - Hierarchical Structure and Catalytic Activity of Flower-Like CeO2 Spheres
      Prepared Via a Hydrothermal Method.
AB  - Hierarchical CeO2 particles were synthesized by a hydrothermal method based on
      the reaction between CeCl3.7H2O and PVP at 270  degrees C. The flower-like CeO2
      with an average diameter of about 1 MUm is composed of compact nanosheets with
      thicknesses of about 15 nm and have a surface area of 36.8 m2/g, a large pore
      volume of 0.109 cm3/g, and a narrow pore size distribution (14.9 nm in diameter).
      The possible formation mechanism of the hierarchical CeO2 nanoparticles has been
      illustrated. The 3D hierarchical structured CeO2 exhibited a higher catalytic
      activity toward CO oxidation compared with commercial CeO2.

PMID- 30274298
TI  - Association of Renal Function and Direct-Acting Antiviral Agents for HCV: A
      Network Meta-Analysis.
AB  - The effectiveness and safety of direct-acting antiviral agents (DAAs) in
      hepatitis C virus (HCV) patients with renal insufficiency remain controversial.
      Therefore, this network meta-analysis aims to assess effectiveness and safety of
      DAAs in populations with different renal function. The pooled data were obtained
      from Cochrane Library, EMBASE, PubMed, and Web of Science. Thirteen studies
      recruited 6884 patients with hepatitis C infection and reported their outcomes in
      relation to different levels of renal function after treatment with DAAs. The
      results showed no difference in the virologic responses among patients with
      different renal function. Regarding safety, whereas in patients without chronic
      kidney disease (CKD) or with early CKD DAAs were associated with a risk ratio
      (RR) of 0.14 (95% confidence interval (CI), 0.04 to 0.43) for renal disorder,
      increased risk of renal function deterioration was found in advanced-CKD
      patients, though this effect may be related to the natural course of advanced
      CKD. Similarly, patients without CKD or with early CKD showed a lower risk of
      anemia (RR, 0.34; 95% CI, 0.20 to 0.57) and discontinuation (RR, 0.41; 95% CI,
      0.39 to 0.56) than patients with advanced CKD. The efficacy of DAAs for HCV
      treatment was comparable in patients with advanced CKD and in those with early
      CKD or without CKD. However, the safety of DAAs should be verified in future
      studies.

PMID- 30274300
TI  - A Label-Free Fluorescent AND Logic Gate Aptasensor for Sensitive ATP Detection.
AB  - In this study, a label-free fluorescent, enzyme-free, simple, highly sensitive
      AND logic gate aptasensor was developed for the detection of adenosine
      triphosphate (ATP). Double-stranded deoxyribonucleic acid (DNA) with cohesive
      ends was attached to graphene oxide (GO) to form an aptasensor probe. ATP and
      single-stranded DNA were used as input signals. Fluorescence intensity of
      PicoGreen dye was used as an output signal. The biosensor-related performances,
      including the logic gate construction, reaction time, linearity, sensitivity, and
      specificity, were investigated and the results showed that an AND logic gate was
      successfully constructed. The ATP detection range was found to be 20 to 400 nM
      (R2 = 0.9943) with limit of detection (LOD) of 142.6 pM, and the sensitivity
      range was 1.846 * 106 to 2.988 * 106 M-1. This method for the detection of ATP
      has the characteristics of being simple, low cost, and highly sensitive.

PMID- 30274302
TI  - Pattern of Paracetamol Poisoning: Influence on Outcome and Complications.
AB  - Acute paracetamol poisoning due to a single overdose may be effectively treated
      by the early administration of N-acetylcysteine (NAC) as an antidote. The
      prognosis may be different in the case of intoxication due to multiple ingestions
      or when the antidote is started with delay. The aim of this work was to
      investigate the outcome of paracetamol poisoning according to the pattern of
      ingestion and determine the factors associated with the outcome. We performed a
      retrospective analysis over the period 2007-2017 of the patients who were
      referred to a tertiary hospital for paracetamol-related hepatotoxicity. Inclusion
      criteria were: accidental or voluntary ingestion of paracetamol, delay for NAC
      therapy of 12 h or more, liver enzymes (ALT) >1000 IU/L on admission. Ninety
      patients were considered. Poisoned patients following multiple ingestion were
      significantly older (45 +/- 12 vs. 33 +/- 14) (p = 0.001), with a higher
      incidence of liver steatosis (p = 0.016) or chronic ethanol abuse (p = 0.04). In
      comparison with the subgroup of favorable outcome, the patients with poor outcome
      were older, had higher values for ALT, bilirubin, lactate, and lower values for
      factor V and arterial pH. In multivariate analysis, the arterial lactate value
      was associated with a bad prognosis (p < 0.02) (adjusted odds ratio 1.74 and CI
      95:1.09-2.77). The risk of poor outcome was greater in the subgroup with
      staggered overdose (p = 0.02), which had a higher mortality rate (p = 0.01). This
      retrospective analysis illustrates the different population patterns of patients
      who were admitted for a single ingestion of a paracetamol overdose versus
      multiple ingestions. This last subgroup was mainly represented by older patients
      with additional risk factors for hepatotoxicity; arterial lactate was a good
      predictor of severity.

PMID- 30274301
TI  - Efficacy Evaluation of Combination Treatment Using Gemcitabine and
      Radioimmunotherapy with 90Y-Labeled Fully Human Anti-CD147 Monoclonal Antibody
      059-053 in a BxPC-3 Xenograft Mouse Model of Refractory Pancreatic Cancer.
AB  - The poor prognosis of pancreatic cancer requires the development of more
      effective therapy. CD147 expresses in pancreatic cancer with high incidence and
      has a crucial role in invasion and metastasis. We developed a fully human
      monoclonal antibody (059-053) with high affinity for CD147. Here we evaluated the
      efficacy of combined treatment using radioimmunotherapy (RIT) with 90Y-labeled
      059-053 and gemcitabine in a BxPC-3 xenograft mouse model. Expression of CD147
      and matrix metalloproteinase-2 (MMP2) in BxPC-3 tumors was evaluated. In vitro
      and in vivo properties of 059-053 were evaluated using 111In-labeled 059-053 and
      a pancreatic cancer model BxPC-3. Tumor volume and body weight were periodically
      measured in mice receiving gemcitabine, RIT, and both RIT and gemcitabine (one
      cycle and two cycles). High expression of CD147 and MMP2 was observed in BxPC-3
      tumors and suppressed by 059-053 injection. Radiolabeled 059-053 bound
      specifically to BxPC-3 cells and accumulated highly in BxPC-3 tumors but low in
      major organs. Combined treatment using RIT with gemcitabine (one cycle)
      significantly suppressed tumor growth and prolonged survival with tolerable
      toxicity. The two-cycle regimen had the highest anti-tumor effect, but was not
      tolerable. Combined treatment with 90Y-labeled 059-053 and gemcitabine is a
      promising therapeutic option for pancreatic cancer.

PMID- 30274303
TI  - The Use of Video Instructions in Patient Education Promoting Correct Technique
      for Dry Powder Inhalers: An Investigation on Inhaler-Naive Individuals.
AB  - Introduction: The correct use of a prescribed inhaler device is crucial for
      achieving successful disease management in asthma. This study investigates non
      verbal, demonstrational videos as a method of teaching inhaler naive individuals
      how to use a dry powder inhaler (DPI). Methods: Video instructions for four DPIs
      were examined using a mixed methodology; 31 inhaler-naive individuals
      participated in the study. Participants were each shown a demonstrational video
      of one the four inhalers, after each video the participant demonstrated how they
      would use the inhaler. After demonstrating the use, participants crossed over to
      the next inhaler. The demonstrations were videotaped. A common questionnaire was
      filled at the beginning of the study and four inhaler-specific questionnaires
      which were filled out by the participant after each inhaler demonstration.
      Results: The frequency of participant error varied between inhalers. When asked
      about how they perceived the video instructions, participants often stated they
      would have liked to receive feedback on their performance. The importance of
      feedback was further highlighted by the fact that participants tended to
      overestimate their own inhaler technique. Conclusion: Non-verbal videos may be
      more efficient for some DPIs than for others as a method for providing inhaler
      instructions. Lack of feedback on the participants' inhaler performance emerged
      as a clear shortcoming of this educational method. Some steps in the inhalation
      process may be harder for individuals to remember and therefore require extra
      emphasis in order to achieve correct inhaler technique.

PMID- 30274304
TI  - MiR-205 Mediated Cu-Induced Lipid Accumulation in Yellow Catfish Pelteobagrus
      fulvidraco.
AB  - The present working hypothesis is that the Cu-induced changes in lipid metabolism
      may be mediated by miRNAs. Here, we describe the miRNA profile of the liver
      tissues of yellow catfish exposed to waterborne Cu, based on larger-scale
      sequencing of small RNA libraries. We identified a total of 172 distinct miRNAs.
      Among these miRNAs, compared to the control, mRNA expression levels of 16 miRNAs
      (miR-203a, 205, 1788-3p, 375, 31, 196a, 203b-3p, 2187-5p, 196d, 459-3p, 153a and
      miR-725, and two novel-miRNAs: chr4-1432, chr-7684) were down-regulated, and mRNA
      levels of miR-212 and chr20-5274 were up-regulated in Cu-exposed group. The
      functions of their target genes mainly involved ether lipid metabolism,
      glycerophospholipid metabolism, linoleic acid metabolism and alpha-linolenic acid
      metabolism. Cu exposure inhibited the expression of miR-205, whose predicted
      target genes were enriched in the pathway of lipid metabolism, including fas,
      lxralpha, ddit3, lamp2, casp3a and baxa. These potential target genes were
      further verified by Dual-luciferase reporter gene assay. Using primary
      hepatocytes of yellow catfish, Cu incubation down-regulated miR-205 expression,
      and increased TG contents and FAS activity. LXR antagonist effectively ameliorate
      the Cu-induced change of TG content and FAS activity. These data suggest that
      down-regulation of the miRNA-205 may be an important step in Cu-induced changes
      in lipid metabolism in yellow catfish.

PMID- 30274305
TI  - Botulinum Toxin in Restless Legs Syndrome-A Randomized Double-Blind Placebo
      Controlled Crossover Study.
AB  - BACKGROUND: Restless Legs Syndrome (RLS) is a common movement disorder with an
      estimated prevalence of up to 12%. Previous small studies with onabotulinumtoxin
      A (OnaA) for RLS have shown inconsistent results. METHODS: Twenty-four patients
      with an International RLS score (IRLS) of >11 (moderate-severe) were enrolled in
      this blinded, placebo-controlled crossover study. Twenty-one patients completed
      the evaluations at 4, 6, and 8 weeks after each injection. One-hundred units of
      Incobotulinumtoxin A (IncoA) or normal saline were injected into tibialis
      anterior, gastrocnemius, and biceps femoris muscles each side. RESULTS:
      Improvement from a severe (IRLS >21) to a mild/moderate (IRLS <=20) score was
      significant at four weeks (p = 0.0036) and six weeks (p = 0.0325) following IncoA
      administration compared to placebo. Additionally, there was significant
      improvement in pain score at six weeks as measured by Visual Analogue Scale (p =
      0.04) and the Johns Hopkins Quality of Life Questionnaire (p = 0.01) in the IncoA
      group. Definite or marked improvement on Patient Global Impression of Change was
      seen in 7 out of 21 patients in the IncoA group vs. 1 out of 21 patients in the
      placebo group at 4 weeks (p = 0.012). CONCLUSION: IncoA injection lead to a
      reduction in severity of RLS symptoms, pain score, and quality of life, without
      any adverse effects.

PMID- 30274307
TI  - HCl Gas Sensor Coating Based on Poly(N-isopropylacrylamide) Nanoparticles
      Prepared from Water-Methanol Binary Solvent.
AB  - Poly(N-isopropylacrylamide) (PNIPAM) nanoparticles formed in water-methanol
      binary solvent were successfully deposited on a resonator surface at room
      temperature by exploiting the cononsolvency effect on the phase transition of
      PNIPAM aqueous solutions. Scanning electron microscopic observation revealed that
      the nanoparticles were secondary and made up of agglomerated primary spherical
      particles of about 10-nm diameter, buried in the film. The magnitude of the
      sensor response toward HCl gas was larger than that of the nanoparticle sensor
      prepared from pure water solvent, and the sensitivity to 1 ppm of HCl of sensor
      coated nanoparticles based on the present method was 3.3 Hz/ppm. The recovery of
      the sensors was less than 90% at first cycle measurement, but had improved to
      almost 100% at the third cycle.

PMID- 30274306
TI  - Photo-Magnetic Irradiation-Mediated Multimodal Therapy of Neuroblastoma Cells
      Using a Cluster of Multifunctional Nanostructures.
AB  - The use of high intensity chemo-radiotherapies has demonstrated only modest
      improvement in the treatment of high-risk neuroblastomas. Moreover, undesirable
      drug specific and radiation therapy-incurred side effects enhance the risk of
      developing into a second cancer at a later stage. In this study, a safer and
      alternative multimodal therapeutic strategy involving simultaneous optical and
      oscillating (AC) magnetic field stimulation of a multifunctional nanocarrier
      system has successfully been implemented to guide neuroblastoma cell destruction.
      This novel technique permitted the use of low-intensity photo-magnetic
      irradiation and reduced the required nanoparticle dose level. The combination of
      released cisplatin from the nanodrug reservoirs and photo-magnetic coupled
      hyperthermia mediated cytotoxicity led to the complete ablation of the B35
      neuroblastoma cells in culture. Our study suggests that smart nanostructure-based
      photo-magnetic hybrid irradiation is a viable approach to remotely guide
      neuroblastoma cell destruction, which may be adopted in clinical management post
      modification to treat aggressive cancers.

PMID- 30274309
TI  - An Optimized Two-Step Magnetic Correction Strategy by Means of a Lagrange
      Multiplier Estimator with an Ellipsoid Constraint.
AB  - The geomagnetic field is as fundamental a constituent of passive navigation as
      Earth's gravity. In cases where no other external attitude reference is
      available, for the direct heading angle estimation by a typical magnetic compass,
      a two-step optimized correction algorithm is proposed to correct the model
      coefficients caused by hard and soft iron nearby. Specifically, in Step 1, a
      Levenberg-Marquardt (L-M) fitting estimator with an ellipsoid constraint is
      applied to solve the hard magnetic coefficients. In Step 2, a Lagrange multiplier
      estimator is used to deal with the soft magnetic iron circumstance. The essential
      attribute of "the two-step" lies in its eliminating the coupling effects of hard
      and soft magnetic fields, and their mutual interferences on the pure geomagnetic
      field. Under the conditions of non-deterministic magnetic interference sources
      with noise, the numerical simulation by referring to International Geomagnetic
      Reference Field (IGRF), and the laboratory tests based upon the turntable
      experiments with Honeywell HMR3000 compass (Honeywell, Morristown, NJ, USA)
      conducted, the experimental results indicate that, in the presence of the
      variation of multi-magnetic interferences, the RMSE (Root Mean Square Error)
      value of the estimated total magnetic flux density by the proposed two-step
      estimator falls to 0.125 MUT from its initial 2.503 MUT, and the mean values of
      the heading angle error estimates are less than 1 degrees . The proposed solution
      therefore, exhibits ideal convergent properties, fairly meeting the accuracy
      requirements of non-tactical level navigation applications.

PMID- 30274308
TI  - Humanin Attenuates NMDA-Induced Excitotoxicity by Inhibiting ROS-dependent
      JNK/p38 MAPK Pathway.
AB  - Humanin (HN) is a novel 24-amino acid peptide that protects neurons against N
      methyl-d-aspartate (NMDA)-induced toxicity. However, the contribution of the
      different mitogen-activated protein kinases (MAPKs) signals to HN neuroprotection
      against NMDA neurotoxicity remains unclear. The present study was therefore aimed
      to investigate neuroprotective mechanisms of HN. We analyzed intracellular Ca2+
      levels, reactive oxygen species (ROS) production, and the MAPKs signal
      transduction cascade using an in vitro NMDA-mediated excitotoxicity of cortical
      neurons model. Results showed that: (1) HN attenuated NMDA-induced neuronal
      insults by increasing cell viability, decreasing lactate dehydrogenase (LDH)
      release, and increasing cell survival; (2) HN reversed NMDA-induced increase in
      intracellular calcium; (3) pretreatment by HN or 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular calcium chelator,
      decreased ROS generation after NMDA exposure; (4) administration of HN or N
      Acetyl-l-cysteine (NAC), a ROS scavenger, inhibited NMDA-induced JNK and p38 MAPK
      activation. These results indicated that HN reduced intracellular elevation of
      Ca2+ levels, which, in turn, inhibited ROS generation and subsequent JNK and p38
      MAPK activation that are involved in promoting cell survival in NMDA-induced
      excitotoxicity. Therefore, the present study suggests that inhibition of ROS
      dependent JNK/p38 MAPK signaling pathway serves an effective strategy for HN
      neuroprotection against certain neurological diseases.

PMID- 30274311
TI  - Addition of Care for Transgender-Related Patient Care into Doctorate of Pharmacy
      Curriculum: Implementation and Preliminary Evaluation.
AB  - The number of transgender and gender-diverse patients seeking medical care in the
      United States is increasing. For many of these patients, pharmacotherapy is a
      part of their gender-affirming transition. Effective instructional methods and
      resources for teaching pharmacy students about this patient population's social
      considerations and medical treatments is lacking. Three hours of educational
      material on caring for transgender patients was added to a third-year course in a
      four-year Doctorate of Pharmacy program in the United States. The content
      included cultural, empathy, and medical considerations. Students in the course
      were given a survey to assess their perception of each instructional method's
      effectiveness and self-assess their confidence in providing competent gender
      affirming care to transgender people before and after the learning session. The
      survey response rate was 36% (54/152). Students' self-assessed confidence to
      provide competent care to people who are transgender increased significantly.
      Before the learning session, the median confidence level was 4/10 (Interquartile
      range (IQR) 3-6), after the class session, the median confidence increased to
      7/10 (IQR 6-8, p < 0.01). Students rated the pre-class video, jeopardy game, and
      patient panel as most helpful to improving their skills. The addition of
      transgender-related patient care material into the Doctorate of Pharmacy
      curriculum significantly increased the students' confidence to provide competent
      care to people who are transgender.

PMID- 30274310
TI  - Current High-Throughput Approaches of Screening Modulatory Effects of Xenobiotics
      on Cytochrome P450 (CYP) Enzymes.
AB  - Cytochrome P450 (CYP) is a critical drug-metabolizing enzyme superfamily.
      Modulation of CYP enzyme activities has the potential to cause drug-drug/herb
      interactions. Drug-drug/herb interactions can lead to serious adverse drug
      reactions (ADRs) or drug failures. Therefore, there is a need to examine the
      modulatory effects of new drug entities or herbal preparations on a wide range of
      CYP isoforms. The classic method of quantifying CYP enzyme activities is based on
      high-performance liquid chromatography (HPLC), which is time- and reagent
      consuming. In the past two decades, high-throughput screening methods including
      fluorescence-based, luminescence-based, and mass-spectrometry-based assays have
      been developed and widely applied to estimate CYP enzyme activities. In general,
      these methods are faster and use lower volume of reagents than HPLC. However,
      each high-throughput method has its own limitations. Investigators may make a
      selection of these methods based on the available equipment in the laboratory,
      budget, and enzyme sources supplied. Furthermore, the current high-throughput
      systems should look into developing a reliable automation mechanism to accomplish
      ultra-high-throughput screening in the near future.

PMID- 30274312
TI  - Identifying Antibacterial Compounds in Black Walnuts (Juglans nigra) Using a
      Metabolomics Approach.
AB  - Black walnut (Juglans nigra L.) is one of the most economically valuable hardwood
      species and a high value tree for edible nut production in the United States.
      Although consumption of black walnut has been linked to multiple health-promoting
      effects (e.g., antioxidant, antimicrobial, anti-inflammatory), the bioactive
      compounds have not been systematically characterized. In addition, the
      associations between different black walnut cultivars and their health-promoting
      compounds have not been well established. In this study, the kernels of twenty
      two black walnut cultivars selected for nut production by the University of
      Missouri Center for Agroforestry (Columbia, MO, USA) were evaluated for their
      antibacterial activities using agar-well diffusion assay. Among the selected
      cultivars, four black walnut cultivars (i.e., Mystry, Surprise, D.34, and A.36)
      exhibited antibacterial activity against a Gram-positive bacterium
      (Staphylococcus aureus), whereas other cultivars showed no effect on the
      inhibition of this bacterium. The antibacterial compounds showing the strongest
      activity were isolated with bioassay-guided purification and identified using a
      metabolomics approach. Six antibacterial bioactive compounds responsible for
      antimicrobial activity were successfully identified. Glansreginin A, azelaic
      acid, quercetin, and eriodictyol-7-O-glucoside are novel antibacterial compounds
      identified in the kernels of black walnuts. The metabolomics approach provides a
      simple and cost-effective tool for bioactive compound identification.

PMID- 30274313
TI  - Molecular Scoring of Hepatocellular Carcinoma for Predicting Metastatic
      Recurrence and Requirements of Systemic Chemotherapy.
AB  - Hepatocellular carcinoma (HCC) causes one of the most frequent cancer-related
      deaths; an HCC subset shows rapid progression that affects survival. We clarify
      molecular features of aggressive HCC, and establish a molecular scoring system
      that predicts metastasis after curative treatment. In total, 125 HCCs were
      examined for TP53, CTNNB1, and TERT promoter mutation, methylation of 8 tumor
      suppressor genes, and 3 repetitive DNA sequences to estimate promoter
      hypermethylation and global hypomethylation. A fractional allelic loss (FAL) was
      calculated to represent chromosomal instability through microsatellite analysis.
      Molecular subclasses were determined using corresponding and hierarchical
      clustering analyses. Next, twenty-five HCC patients who underwent liver
      transplantation were analyzed for associations between molecular characteristics
      and metastatic recurrence; survival analyses were validated using a publicly
      available dataset of 376 HCC cases from the Cancer Genome Atlas (TCGA). An HCC
      subtype characterized by TP53 mutation, high FAL, and global hypomethylation was
      associated with aggressive tumor characteristics, like vascular invasion; CTNNB1
      mutation was a feature of the less-progressive phenotype. A number of molecular
      risk factors, including TP53 mutation, high FAL, significant global
      hypomethylation, and absence of CTNNB1 mutation, were noted to predict shorter
      recurrence-free survival in patients who underwent liver transplantation (p =
      0.0090 by log-rank test). These findings were validated in a cohort of resected
      HCC cases from TCGA (p = 0.0076). We concluded that molecular risks determined by
      common genetic and epigenetic alterations could predict metastatic recurrence
      after curative treatments, and could be a marker for considering systemic therapy
      for HCC patients.

PMID- 30274315
TI  - The Effect of Neonicotinoid Insecticide and Fungicide on Sugar Responsiveness and
      Orientation Behavior of Honey Bee (Apis mellifera) in Semi-Field Conditions.
AB  - Neonicotinoid insecticides are in widespread use around the world, cause
      pollinator decline. We used semi-field conditions to determine the effect of
      sublethal insecticide, thiamethoxam, exposure on orientation behavior and sugar
      responsiveness. Bees could not reject the non-treated flower or the insecticide
      or insecticide/fungicide treated flower. After bees consumed the insecticide or
      insecticide/fungicide treated nectar, they could not discriminate between a
      flower odor or blank control in a Y-maze when making a first choice. We also
      found that treated bees wander back and forth in both arms to make a final
      decision about food location, and used longer duration in the Y maze than the
      control group. Sugar responsiveness was also reduced after bees were fed with
      insecticide or insecticide/fungicide treated food, one week was needed for them
      to display the same level of responsiveness as the control group. The
      thiamethoxam or thiamethoxam/carbendazol treated crop field does not act as an
      olfactory repellent to the bee, but it does affect its post-consumption behavior.

PMID- 30274314
TI  - Anthocyanins Extracted from Oryza sativa L. Prevent Fluorouracil-Induced Nuclear
      Factor-kappaB Activation in Oral Mucositis: In Vitro and In Vivo Studies.
AB  - This study aims to investigate the immunomodulatory effect of anthocyanins (ANTs)
      from Oryza sativa L. extracts on 5-fluorouracil (5-FU)-induced oral mucositis,
      using a rat model and oral keratinocytes. ANTs were detected by high-performance
      liquid chromatography (HPLC)-electrospray ionization mass spectrometry. Animals
      were randomly given varying doses of ANT-rich extract treatment (500 mg/kg and
      1000 mg/kg) in the absence or presence of 5-FU-induced mucositis. Buccal mucosae
      were photographed and scored for macroscopic analysis and incisional biopsies of
      cheek pouches were collected for microscopic examination of oral mucositis. 5-FU
      caused marked hemorrhage, extensive ulcerations and abscesses compared to non
      treated animals with slight erythema. Histologically, a loss of collagen bundles
      and inflammatory cell infiltrates was observed. After 29 days of ANT treatment,
      lesions resolved, and abundant collagen fibers were evident in the lamina
      propria. Buccal mucosa of 5-FU-injected rats showed increased Nuclear factor
      kappa B (NF-kappaB) p50 and p65 in oral keratinocytes. The administration of ANT
      reduced NF-kappaB-positive cells in 5-FU rats (p < 0.001) compared to the non
      treatment group. In oral keratinocytes, ANT treatment significantly restored 5-FU
      induced growth inhibition and impaired the nuclear accumulation of NF-kappaB p50
      and p65. Our study demonstrated that ANT from Oryza sativa L. exhibited effective
      anti-inflammatory properties against 5-FU-induced oral mucositis by inhibiting NF
      kappaB activation.

PMID- 30274316
TI  - Phosphoric Acid Doped Polybenzimidazole (PBI)/Zeolitic Imidazolate Framework
      Composite Membranes with Significantly Enhanced Proton Conductivity under Low
      Humidity Conditions.
AB  - The preparation and characterization of composite polybenzimidazole (PBI)
      membranes containing zeolitic imidazolate framework 8 (ZIF-8) and zeolitic
      imidazolate framework 67 (ZIF-67) is reported. The phosphoric acid doped
      composite membranes display proton conductivity values that increase with
      increasing temperatures, maintaining their conductivity under anhydrous
      conditions. The addition of ZIF to the polymeric matrix enhances proton transport
      relative to the values observed for PBI and ZIFs alone. For example, the proton
      conductivity of PBI@ZIF-8 reaches 3.1 * 10-3 S.cm-1 at 200  degrees C and higher
      values were obtained for PBI@ZIF-67 membranes, with proton conductivities of up
      to 4.1 * 10-2 S.cm-1. Interestingly, a composite membrane containing a 5 wt.%
      binary mixture of ZIF-8 and ZIF-67 yielded a proton conductivity of 9.2 * 10-2
      S.cm-1, showing a synergistic effect on the proton conductivity.

PMID- 30274317
TI  - PEGylation of Superparamagnetic Iron Oxide Nanoparticles with Self-Organizing
      Polyacrylate-PEG Brushes for Contrast Enhancement in MRI Diagnosis.
AB  - For biomedical applications, superparamagnetic nanoparticles (MNPs) have to be
      coated with a stealth layer that provides colloidal stability in biological
      media, long enough persistence and circulation times for reaching the expected
      medical aims, and anchor sites for further attachment of bioactive agents. One of
      such stealth molecules designed and synthesized by us, poly(polyethylene glycol
      methacrylate-co-acrylic acid) referred to as P(PEGMA-AA), was demonstrated to
      make MNPs reasonably resistant to cell internalization, and be an excellent
      candidate for magnetic hyperthermia treatments in addition to possessing the
      necessary colloidal stability under physiological conditions (Illes et al. J.
      Magn. Magn. Mater. 2018, 451, 710-720). In the present work, we elaborated on the
      molecular background of the formation of the P(PEGMA-AA)-coated MNPs, and of
      their remarkable colloidal stability and salt tolerance by using potentiometric
      acid-base titration, adsorption isotherm determination, infrared spectroscopy (FT
      IR ATR), dynamic light scattering, and electrokinetic potential determination
      methods. The P(PEGMA-AA)@MNPs have excellent blood compatibility as demonstrated
      in blood sedimentation, smears, and white blood cell viability experiments. In
      addition, blood serum proteins formed a protein corona, protecting the particles
      against aggregation (found in dynamic light scattering and electrokinetic
      potential measurements). Our novel particles also proved to be promising
      candidates for MRI diagnosis, exhibiting one of the highest values of r2
      relaxivity (451 mM-1s-1) found in literature.

PMID- 30274318
TI  - Birefringent Bragg Grating in C-Shaped Optical Fiber as a Temperature-Insensitive
      Refractometer.
AB  - We demonstrate a simple-to-fabricate refractometer based on the inscription of
      fiber Bragg gratings in a special C-shaped optical fiber. The C-shaped fiber was
      drawn into shape using a quarter cladding removed preform of a commercial
      standard single-mode fiber by simple machining. The sensor did not suffer from
      cross-sensitivity of the refractive index with ambient temperature fluctuations,
      commonly occurring with many optical fiber refractometers. A refractive index
      sensitivity of 1300 pm per refractive index unit (RIU) was achieved without
      employing any additional sensitization techniques such as tapering or etching.

PMID- 30274320
TI  - Study on the Classification, Causality, Preventability and Severity of Adverse
      Drug Reaction Using Spontaneous Reporting System in Hospitalized Patients.
AB  - Hospital-based adverse drug reaction (ADR) monitoring and reporting programs
      intend to identify and quantify the risks associated with the use of medicines.
      To examine the causality, preventability and severity of ADR in a hospital
      setting; a prospective cohort study on spontaneous ADR reporting was conducted
      from December 2015 to May 2016. Incidence of ADRs, causality, type, severity and
      preventability were assessed using necessary assessment scales. The study
      included 3157 hospitalized individuals, in whom 51 ADRs were detected among 49
      patients. The overall incidence of suspected ADRs was found to be 1.6%. According
      to the causality assessment, most of the ADRs reported were probable (n = 26,
      51.0%), and type A (augmented/pharmacological) reactions (n = 39, 76%) were the
      most common type of ADR found. The majority of ADRs were moderate to severe (n =
      35, 68.6%), of which 37.3% were found to be potentially preventable.
      Predictability was observed in 28 (54.9%) reported ADRs. The prescribed medicines
      most frequently associated with ADRs were antibiotics, antiepileptics and
      antihypertensives. This feasibility study was able to highlight the clinical
      pharmacist's role in ADR monitoring service and create awareness about the way it
      could be done to promote safer medication use. Similar ADR reporting programs are
      necessary to educate and to improve awareness among healthcare professionals in
      some countries.

PMID- 30274319
TI  - Capillary Blood GSH Level Monitoring, Using an Electrochemical Method Adapted for
      Micro Volumes.
AB  - Glutathione (gamma-glutamyl-cysteinyl-glycine; also known as GSH) is an
      endogenous antioxidant that plays a crucial role in cell defense mechanisms
      against oxidative stress. It is thus not surprising that this molecule can serve
      as a biomarker for oxidative stress monitoring. As capillary blood is a highly
      accessible target for biomarking, it is a valuable bodily fluid for diagnosing
      human GSH levels. This study focused on the optimization of GSH measurements from
      micro volumes of capillary blood prior to using electrochemical detection. The
      optimization of experimental parameters, including the sample volume and its
      stability, was performed and evaluated. Moreover, we tested the optimized method
      as part of a short-term study. The study consisted of examining 10 subjects
      within 96 h of their consumption of high amounts of antioxidants, attained from a
      daily dose of 2 g/150 mL of green tea. The subjects' capillary blood (5 MUL) was
      taken at 0 h, 48 h, and 96 h for subsequent analysis. The short-term
      supplementation of diet with green tea showed an increase of GSH pool by
      approximately 38% (between 0 and 48 h) within all subjects.

PMID- 30274321
TI  - Correction: de Gonzalo, G. Lipase Catalysed Kinetic Resolution of Racemic 1,2
      Diols Containing a Chiral Quaternary Center. Molecules 2018, 23, 1585.

PMID- 30274322
TI  - Depression Negatively Impacts Survival of Patients with Metastatic Prostate
      Cancer.
AB  - The prevalence of depression in patients with cancer is high, especially for
      patients with advanced cancer. In this study, we evaluated the prevalence of
      depression in prostate cancer patients in Taiwan and the association between
      depression and mortality in prostate cancer. This study included 1101 newly
      diagnosed patients with prostate cancer. We tracked the medical information of
      these patients from diagnosis until the end of 2012. Patients were divided into
      two groups according to presence or absence of depression diagnosis, and were
      further divided into three stages by initial treatments: localized or locally
      advanced, metastatic, and castration-resistant prostate cancer. Of 1101
      participants, 267 (24.3%) had depression. By the end of the follow-up period (M =
      8.30 +/- 3.12 years), 77 (28.8%) patients in the depression group and 194 (23.3%)
      in the non-depressed group died. Depression was associated with higher mortality
      risk, (aHR 1.37; 95% CI [ 1.04-1.80]; p value 0.01). Patients in the metastatic
      prostate cancer group with depression had a significantly higher mortality risk
      compared to the non-depressed group, (aHR, 1.49; 95% CI [1.05-2.11]; p value
      0.02). The impact of depression on mortality risk was not significant in either
      the localized or locally advanced or the castration-resistant prostate cancer
      groups. Our study showed that depression is related to an increased mortality
      risk for patients with prostate cancer, especially for metastatic prostate
      cancer. These results indicate that urologists should pay attention to the mood
      and psychiatric disorders of patients with prostate cancer.

PMID- 30274324
TI  - Biosynthesis of Grandione: An Example of Tandem Hetero Diels-Alder/Retro-Claisen
      Rearrangement Reaction?
AB  - Mechanistic theoretical studies about the feasibility of the traditional proposed
      mechanism of formation for icetexane diterpene dimer grandione were assessed
      using density functional method at the M06-2X/6-31G(d,p) level of theory. Bulk
      water solvent effects were taken into account implicitly using the polarizable
      continuum model (SCI-PCM). The results were compared with the selectivity found
      in the biomimetic synthesis performed by experimental research groups. The
      relative free energy calculation shows that the one-step H-DA formation mechanism
      nominated in the literature is not a viable mechanism. We found that an
      alternative competing Tandem pathway is consistent with the experimental trends.
      Thus, our results suggested that the compound grandione is formed via a H
      DA/retro-Claisen rearrangement and not by the traditional H-DA mechanism proposed
      early in the experimental studies. The H-DA initial step produce a biecyclic
      adduct followed by a domino retro-Claisen rearrangement that releases the energy
      strain of the bicyclic intermediary. Steric issues and hyperconjugation
      interactions are the mainly factors driving the reaction nature and the
      selectivity in the formation reaction. Finally, the enzymatic assistance for
      dimer formation was analyzed in terms of the calculated transition state energy
      barrier.

PMID- 30274323
TI  - Progress in Optimization of Agrobacterium-Mediated Transformation in Sorghum
      (Sorghum bicolor).
AB  - This review archives the achievements made in the last two decades and presents a
      brief outline of some significant factors influencing the Agrobacterium-mediated
      transformation of Sorghum bicolor. Recently, progress in successful
      transformation has been made for this particular monocot crop through direct DNA
      delivery method and indirect method via Agrobacterium. However, lower
      transformation rate still proved to be a bottleneck in genetic modification of
      sorghum. An efficient Agrobacterium transformation system could be attained by
      optimizing the preliminary assays, comprising of explant source, growth media,
      antibiotics, Agrobacterium strains and agro-infection response of callus. The
      selection of competent strains for genetic transformation is also one of the key
      factors of consideration. Successful transformation is highly dependent on genome
      configuration of selected cultivar, where non-tannin genotype proved the best
      suited. Immature embryos from the field source have higher inherent adaptation
      chances than that of the greenhouse source. A higher concentration of
      Agrobacterium may damage the explant source. Utilization of anti-necrotic
      treatments and optimized tissue culture timeframe are the adequate strategies to
      lower down the effect of phenolic compounds. Appropriate selection of culture
      media vessels at different stages of tissue culture may also assist in a
      constructive manner. In conclusion, some aspects such as culture environment with
      medium composition, explant sources, and genotypes play an indispensable role in
      successful Agrobacterium-mediated sorghum transformation system.

PMID- 30274326
TI  - When to Initiate Weight Loss Medications in the NAFLD Population.
AB  - Nonalcoholic fatty liver disease (NAFLD) is characterized by histological
      evidence of hepatic steatosis, lobular inflammation, ballooning degeneration and
      hepatic fibrosis in the absence of significant alcohol use and other known causes
      of chronic liver diseases. NAFLD is subdivided into nonalcoholic fatty liver
      (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is generally benign but can
      progress to NASH, which carries a higher risk of adverse outcomes including
      cirrhosis, end-stage liver disease, hepatocellular carcinoma and death if liver
      transplantation is not pursued in a timely fashion. Currently, lifestyle
      modifications including healthy diet and increased physical activity/exercise
      culminating in weight loss of 5% to >10% is the cornerstone of treatment
      intervention for patients with NAFLD. Patients with NAFLD who fail to obtain this
      goal despite the help of dietitians and regimented exercise programs are left in
      a purgatory state and remain at risk of developing NASH-related advance fibrosis.
      For such patients with NAFLD who are overweight and obese, healthcare providers
      should consider a trial of FDA-approved anti-obesity medications as adjunct
      therapy to provide further preventative and therapeutic options as an effort to
      reduce the risk of NAFLD-related disease progression.

PMID- 30274325
TI  - Dietary Fats and Chronic Noncommunicable Diseases.
AB  - The role of dietary fat has been long studied as a modifiable variable in the
      prevention and treatment of noncommunicable cardiometabolic disease. Once heavily
      promoted to the public, the low-fat diet has been demonstrated to be non
      effective in preventing cardiometabolic disease, and an increasing body of
      literature has focused on the effects of a relatively higher-fat diet. More
      recent evidence suggests that a diet high in healthy fat, rich in unsaturated
      fatty acids, such as the Mediterranean dietary pattern, may, in fact, prevent the
      development of metabolic diseases such as type 2 diabetes mellitus, but also
      reduce cardiovascular events. This review will specifically focus on clinical
      trials which collected data on dietary fatty acid intake, and the association of
      these fatty acids over time with measured cardiometabolic health outcomes,
      specifically focusing on morbidity and mortality outcomes. We will also describe
      mechanistic studies investigating the role of dietary fatty acids on
      cardiovascular risk factors to describe the potential mechanisms of action
      through which unsaturated fatty acids may exert their beneficial effects. The
      state of current knowledge on the associations between dietary fatty acids and
      cardiometabolic morbidity and mortality outcomes will be summarized and
      directions for future work will be discussed.

PMID- 30274328
TI  - Does Early Recruitment Predict Greater Physical Performance in Academy Soccer
      Players?
AB  - The purpose of this longitudinal study was to investigate whether recruitment
      status influences neuromuscular and endurance performances in academy soccer
      players over a 2-year training period (from Under-16 to Under-18). Thirty-seven
      male soccer players from an elite academy were selected and divided in two
      cohorts according to their recruitment status: Early Recruitment group (ER; n =
      16), training and competing for the academy since Under-14 and Under-15 age
      groups, and; Late Recruitment group (LR; n = 21) included in the academy training
      process at Under-16. Squat (SJ) and countermovement jump with (CMJwA) and without
      arms swing (CMJ), 10-m sprint time, and Vam-Eval test (MAV) were performed in
      three successive occasions always pre-season (Under-16, Under-17 and Under-18 age
      groups, T1, T2, and T3 respectively). A two-way (recruitment status * time)
      analysis of variance with repeated measurements was performed as well as the
      magnitude of difference using both effect size and magnitude-based inferences.
      There was no difference between ER and LR for MAV, 10 m-sprint, and SJ from T1 to
      T3. However, LR players presented non-significant small and possibly greater
      improvement in CMJ (ES = 0.4) and CMJwA (ES = 0.4) than ER players at T2. These
      data indicate that early recruitment is not likely to result in greater physical
      performance improvement at the age of 18.

PMID- 30274327
TI  - The Acute Effects of Caffeinated Black Coffee on Cognition and Mood in Healthy
      Young and Older Adults.
AB  - Cognitive and mood benefits of coffee are often attributed to caffeine. However,
      emerging evidence indicates behavioural effects of non-caffeine components within
      coffee, suggesting the potential for direct or synergistic effects of these
      compounds when consumed with caffeine in regular brewed coffee. The current
      randomised, placebo-controlled, double-blind, counterbalanced-crossover study
      compared the effects of regular coffee, decaffeinated coffee, and placebo on
      measures of cognition and mood. Age and sex effects were explored by comparing
      responses of older (61-80 years, N = 30) and young (20-34 years, N = 29) males
      and females. Computerised measures of episodic memory, working memory, attention,
      and subjective state were completed at baseline and 30 min post-drink. Regular
      coffee produced the expected effects of decreased reaction time and increased
      alertness when compared to placebo. When compared to decaffeinated coffee,
      increased digit vigilance accuracy and decreased tiredness and headache ratings
      were observed. Decaffeinated coffee also increased alertness when compared to
      placebo. Higher jittery ratings following regular coffee in young females and
      older males represented the only interaction of sex and age with treatment. These
      findings suggest behavioural activity of coffee beyond its caffeine content,
      raising issues with the use of decaffeinated coffee as a placebo and highlighting
      the need for further research into its psychoactive effects.

PMID- 30274329
TI  - Prevalence and Clinical Significance of Symptoms at Ultra High Risk for Psychosis
      in Children and Adolescents with Obsessive-Compulsive Disorder: Is There an
      Association with Global, Role, and Social Functioning?
AB  - In literature nothing is known about the clinical significance of Ultra High Risk
      (UHR) symptoms in children and adolescents with diagnosis of obsessive-compulsive
      disorder (OCD). In this study, we examined the prevalence of UHR symptoms and
      their relationship with severity of obsessive-compulsive symptomatology, global,
      social, and role functioning, and level of associated depressive symptoms in a
      clinical sample (n = 51) of children and adolescents aged between 8 and 17 years
      with a diagnosis of OCD. The prevalence of UHR symptoms in this sample was 43.1%.
      We divided the whole sample into two groups: children and adolescents with OCD
      and UHR symptoms (n = 22) and children and adolescents with OCD without UHR
      symptoms (n = 29). Our findings suggest that the group with OCD and UHR symptoms
      shows worse global, social, and role functioning than the group with OCD without
      UHR symptoms. No differences were found on the severity of obsessive-compulsive
      symptomatology, the number of psychiatric diagnoses associated, and the level of
      depressive symptoms. The presence of UHR symptoms in children and adolescents
      with OCD could cause significant functional impairment and should be considered
      in order to plan specific and targeted therapeutic interventions.

PMID- 30274330
TI  - Photothermal Off-Resonance Tapping for Rapid and Gentle Atomic Force Imaging of
      Live Cells.
AB  - Imaging living cells by atomic force microscopy (AFM) promises not only high
      resolution topographical data, but additionally, mechanical contrast, both of
      which are not obtainable with other microscopy techniques. Such imaging is
      however challenging, as cells need to be measured with low interaction forces to
      prevent either deformation or detachment from the surface. Off-resonance modes
      which periodically probe the surface have been shown to be advantageous, as they
      provide excellent force control combined with large amplitudes, which help reduce
      lateral force interactions. However, the low actuation frequency in traditional
      off-resonance techniques limits the imaging speed significantly. Using
      photothermal actuation, we probe the surface by directly actuating the
      cantilever. Due to the much smaller mass that needs to be actuated, the
      achievable measurement frequency is increased by two orders of magnitude.
      Additionally, photothermal off-resonance tapping (PORT) retains the precise force
      control of conventional off-resonance modes and is therefore well suited to
      gentle imaging. Here, we show how photothermal off-resonance tapping can be used
      to study live cells by AFM. As an example of imaging mammalian cells, the initial
      attachment, as well as long-term detachment, of human thrombocytes is presented.
      The membrane disrupting effect of the antimicrobial peptide CM-15 is shown on the
      cell wall of Escherichia coli. Finally, the dissolution of the cell wall of
      Bacillus subtilis by lysozyme is shown. Taken together, these evolutionarily
      disparate forms of life exemplify the usefulness of PORT for live cell imaging in
      a multitude of biological disciplines.

PMID- 30274331
TI  - Radon in Schools: A Brief Review of State Laws and Regulations in the United
      States.
AB  - Exposure to Radon, a colorless, naturally occurring radioactive gas, is one of
      leading causes of lung cancer, and may pose a significant long-term risk for
      school age children. We examined the regulations and statutes in each US state
      related to radon in schools to delineate key features of policies and
      discrepancies among states that may have public health implications. Search terms
      such as "radon", "school", "mitigation", "certification", "licensing", and "radon
      resistant new construction" were used to scan current statutes from each state
      legislature's website and regulations from official state government websites for
      relevant regulatory and statutory requirements concerning radon in schools. State
      regulations related to the testing, mitigation, and public dissemination of radon
      levels in schools are inconsistent and the lack of nationwide indoor radon policy
      for schools may result in unacceptably high radon exposure levels in some US
      schools. We highlight the features and discrepancies of state laws and
      regulations concerning radon in schools, and offer several constructive means to
      reduce risks associated with radon exposure in school children.

PMID- 30274332
TI  - Main Allelochemicals from the Rhizosphere Soil of Saussurea lappa (Decne.) Sch.
      Bip. and Their Effects on Plants' Antioxidase Systems.
AB  - Allelochemicals are the media of allelopathy and form the chemical bases of plant
      environment interactions. To determine true allelochemicals and their autotoxic
      effects, seven compounds were isolated and identified from in-situ sampled
      rhizosphere soil of cultivated Saussurea lappa. Of these; costunolide (2),
      dehydrocostus lactone (3) and scopoletin (4) showed significant inhibition on
      seedling growth in a concentration-dependent manner. Detection and observation
      demonstrated that the antioxidase system was found to be affected by these
      chemicals, resulting in the accumulation of ROS and membrane damage. To
      investigate their release ways, the compounds were traced back and volumes
      quantified in rhizosphere soil and plant tissues. This work made clear the
      chemical bases and their physiological effects on the plants. These chemicals
      were found to be the secondary metabolites of the plants and included in the
      rhizosphere soil. The findings identified a potential pathway of plant-plant
      interactions, which provided theoretical basis to overcoming replanting problems.
      This research was also useful for exploring ecological effects of allelochemicals
      in green agriculture.

PMID- 30274334
TI  - Metabolomic Investigations on Nesterenkonia flava Revealed Significant
      Differences between Marine and Terrestrial Actinomycetes.
AB  - Marine microorganisms are an important source of natural products with potent
      bioactivities. Unlike the land, the ocean, especially the deep-sea, is
      characterized by high pressure, high salinity, low nutrition, and no light among
      others. Therefore, the biodiversity of marine microorganisms is supposed to be
      very different from that of the terrestrial ones. Yet, many marine microorganisms
      can find their counterparts in terrestrial environments. To evaluate their
      differences, a comparative metabolomics investigation was performed on four
      strains of Nesterenkonia flava isolated from terrestrial and marine environments.
      As a result, marine strains were clearly distinguished from terrestrial ones on
      the principal components analysis (PCA) score plot. Furthermore, by partial least
      squares discrimination analysis (PLS-DA) and univariate analysis, the
      characteristic metabolites were figured out and found to be involved in osmotic
      regulation, redox balancing, and energy metabolism. Our results demonstrated that
      marine actinomycetes could produce novel secondary metabolites different from
      their terrestrial relatives because they have special metabolic patterns closely
      related to the unique features of their living environment.

PMID- 30274335
TI  - An Experiment on the Psychological and Physiological Effects of Skin
      Moisturization on Lower Legs-In Expectation of Application to Nursing Practice at
      Hospitals.
AB  - This study hypothesized that moisturizing treatment of the skin has a positive
      effect on psychological and physiological aspects. In this experiment, the effect
      of touch with moisturizer for two minutes on the lower legs was measured in terms
      of brain activity, heart rate, and center of gravity unrest (X axis) in 10
      healthy male and female experiment participants. The Right Laterality Ratio Score
      decreased after treatment, suggesting a relaxation effect of the treatment.
      Although it was not statistically significant, a decrease was observed. Heart
      rate decreased after the treatment at a level of statistical significance (p <
      0.01), suggesting a relaxation effect of the treatment. Center of gravity unrest
      (X axis) increased after the treatment with statistical significance (p < 0.05).
      Therefore, skin moisturizing treatment was found to be effective both
      psychologically and physiologically in this experiment. The finding is expected
      to be applied to the field of nursing to support elderly people to enhance their
      mental well-being and balancing ability.

PMID- 30274333
TI  - Visualization of HIV-1 RNA Transcription from Integrated HIV-1 DNA in Reactivated
      Latently Infected Cells.
AB  - We have recently developed the first microscopy-based strategy that enables
      simultaneous multiplex detection of viral RNA (vRNA), viral DNA (vDNA), and viral
      protein. Here, we used this approach to study the kinetics of latency
      reactivation in cells infected with the human immunodeficiency virus (HIV). We
      showed the transcription of nascent vRNA from individual latently integrated and
      reactivated vDNA sites appearing earlier than viral protein. We further
      demonstrated that this method can be used to quantitatively assess the efficacy
      of a variety of latency reactivating agents. Finally, this microscopy-based
      strategy was augmented with a flow-cytometry-based approach, enabling the
      detection of transcriptional reactivation of large numbers of latently infected
      cells. Hence, these approaches are shown to be suitable for qualitative and
      quantitative studies of HIV-1 latency and reactivation.

PMID- 30274336
TI  - Effects of Conservative Tillage and Nitrogen Management on Weed Seed Bank after a
      Seven-Year Durum Wheat-Faba Bean Rotation.
AB  - Conservative agriculture includes a range of management strategies with low
      energy inputs such as no-tillage, minimum tillage, and low application of
      fertilizers. Weed flora in arable fields is strictly affected by agronomic
      practices such as tillage and fertilization management. This study was conducted
      seven years after the beginning of a long-term-durum wheat-faba bean-rotation. It
      analyzes the combined effects on the soil seed bank of three different tillage
      systems (conservative, reduced, and conventional tillage) and two levels of
      nitrogen fertilization. The effects were investigated both using stepwise
      discriminant analysis and analysis of variance in order to find statistical
      differences among main factors and their interactions. The seed bank of Conyza
      canadensis, Papaver rhoeas, Solanum nigrum, Fallopia convolvulus, and Fumaria
      officinalis was higher in conservative or reduced tillage plots. The magnitude of
      the response to nitrogen supply varied among weed species. Conyza canadensis
      seemed to be favored by low nitrogen supply, whereas Sinapis arvensis by higher
      doses of nitrogen. Anagallis arvensis showed the lowest seed bank in
      conventionally tilled plots, without distinction of nitrogen supply. The results
      suggest that different tillage systems and, to a lesser extent, different
      nitrogen supply, produce changes in the seed bank size and composition, along the
      soil profile.

PMID- 30274337
TI  - Gene Delivery into the Inner Ear and Its Clinical Implications for Hearing and
      Balance.
AB  - The inner ear contains many types of cell, including sensory hair cells and
      neurons. If these cells are damaged, they do not regenerate. Inner ear disorders
      have various etiologies. Some are related to aging or are idiopathic, as in
      sudden deafness. Others occur due to acoustic trauma, exposure to ototoxic drugs,
      viral infections, immune responses, or endolymphatic hydrops (Meniere's disease).
      For these disorders, inner ear regeneration therapy is expected to be a feasible
      alternative to cochlear implants for hearing recovery. Recently, the mechanisms
      underlying inner ear regeneration have been gradually clarified. Inner ear cell
      progenitors or stem cells have been identified. Factors necessary for
      regeneration have also been elucidated from the mechanism of hair cell
      generation. Inducing differentiation of endogenous stem cells or inner ear stem
      cell transplantation is expected. In this paper, we discuss recent approaches to
      hair cell proliferation and differentiation for inner ear regeneration. We
      discuss the future road map for clinical application. The therapies mentioned
      above require topical administration of transgenes or drug onto progenitors of
      sensory cells. Developing efficient and safe modes of administration is
      clinically important. In this regard, we also discuss our development of an inner
      ear endoscope to facilitate topical administration.

PMID- 30274338
TI  - Domain Adaptation and Adaptive Information Fusion for Object Detection on Foggy
      Days.
AB  - Foggy days pose many difficulties for outdoor camera surveillance systems. On
      foggy days, the optical attenuation and scattering effects of the medium
      significantly distort and degenerate the scene radiation, making it noisy and
      indistinguishable. Aiming to solve this problem, in this paper we propose a novel
      object detection method that has the ability to exploit the information in the
      color and depth domains. To prevent the error propagation problem, we clean the
      depth information before the training process and remove false samples from the
      database. A domain adaptation strategy is employed to adaptively fuse the
      decisions obtained in the color and depth domains. In the experiments, we
      evaluate the contribution of the depth information for object detection on foggy
      days. Moreover, the advantages of the multiple-domain adaptation strategy are
      experimentally demonstrated via comparison with other methods.

PMID- 30274339
TI  - A Unique Naphthone Derivative and a Rare 4,5-seco-Lanostane Triterpenoid from
      Poria cocos.
AB  - A previously undescribed naphthalenone derivative, sohiracillinone (1), and a
      novel 4,5-seco-lanostane triterpenoid, 11beta-ethoxydaedaleanic acid A (2) were
      isolated with two new lanostane triterpenoids, ceanphytamic acids A (3) and B
      (4), from the EtOH extract of Poria cocos along with 17 known compounds 5-21. The
      absolute configuration of sohiracillinone (1) was unambiguously identified by NMR
      and electronic circular dichroism (ECD) data. The structures of other new
      compounds were elucidated on the basis of NMR and mass spectroscopy (MS), and the
      cytotoxic activities of all the isolated components were evaluated.

PMID- 30274340
TI  - A Validation Study of Freezing of Gait (FoG) Detection and Machine-Learning-Based
      FoG Prediction Using Estimated Gait Characteristics with a Wearable
      Accelerometer.
AB  - One of the most common symptoms observed among most of the Parkinson's disease
      patients that affects movement pattern and is also related to the risk of fall,
      is usually termed as "freezing of gait (FoG)". To allow systematic assessment of
      FoG, objective quantification of gait parameters and automatic detection of FoG
      are needed. This will help in personalizing the treatment. In this paper, the
      objectives of the study are (1) quantification of gait parameters in an objective
      manner by using the data collected from wearable accelerometers; (2) comparison
      of five estimated gait parameters from the proposed algorithm with their
      counterparts obtained from the 3D motion capture system in terms of mean error
      rate and Pearson's correlation coefficient (PCC); (3) automatic discrimination of
      FoG patients from no FoG patients using machine learning techniques. It was found
      that the five gait parameters have a high level of agreement with PCC ranging
      from 0.961 to 0.984. The mean error rate between the estimated gait parameters
      from accelerometer-based approach and 3D motion capture system was found to be
      less than 10%. The performances of the classifiers are compared on the basis of
      accuracy. The best result was accomplished with the SVM classifier with an
      accuracy of approximately 88%. The proposed approach shows enough evidence that
      makes it applicable in a real-life scenario where the wearable accelerometer
      based system would be recommended to assess and monitor the FoG.

PMID- 30274341
TI  - Hits-to-Lead Optimization of the Natural Compound 2,4,6-Trihydroxy-3-geranyl
      acetophenone (tHGA) as a Potent LOX Inhibitor: Synthesis, Structure-Activity
      Relationship (SAR) Study, and Computational Assignment.
AB  - A new series of 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA) analogues were
      synthesized and evaluated for their lipoxygenase (LOX) inhibitory activity.
      Prenylated analogues 4a-g (half maximal inhibitory concentration (IC50) values
      ranging from 35 MU M to 95 MU M) did not exhibit better inhibitory activity than
      tHGA (3a) (IC50 value: 23.6 MU M) due to the reduction in hydrophobic interaction
      when the alkyl chain length was reduced. One geranylated analogue, 3d, with an
      IC50 value of 15.3 MU M, exhibited better LOX inhibitory activity when compared
      to tHGA (3a), which was in agreement with our previous findings. Kinetics study
      showed that the most active analogue (3e) and tHGA (3a) acted as competitive
      inhibitors. The combination of in silico approaches of molecular docking and
      molecular dynamic simulation revealed that the lipophilic nature of these
      analogues further enhanced the LOX inhibitory activity. Based on absorption,
      distribution, metabolism, excretion, and toxicity (ADMET) and toxicity prediction
      by komputer assisted technology (TOPKAT) analyses, all geranylated analogues (3a
      g) showed no hepatotoxicity effect and were biodegradable, which indicated that
      they could be potentially safe drugs for treating inflammation.

PMID- 30274342
TI  - Expression of a Grape VqSTS36-Increased Resistance to Powdery Mildew and Osmotic
      Stress in Arabidopsis but Enhanced Susceptibility to Botrytis cinerea in
      Arabidopsis and Tomato.
AB  - Stilbene synthase genes make a contribution to improving the tolerances of biotic
      and abiotic stress in plants. However, the mechanisms mediated by these STS genes
      remain unclear. To provide insight into the role of STS genes defense against
      biotic and abiotic stress, we overexpressed VqSTS36 in Arabidopsis thaliana and
      tomato (Micro-Tom) via Agrobacterium-mediated transformation. VqSTS36-transformed
      Arabidopsis lines displayed an increased resistance to powdery mildew, but both
      VqSTS36-transformed Arabidopsis and tomato lines showed the increased
      susceptibility to Botrytis cinerea. Besides, transgenic Arabidopsis lines were
      found to confer tolerance to salt and drought stress in seed and seedlings. When
      transgenic plants were treated with a different stress, qPCR assays of defense
      related genes in transgenic Arabidopsis and tomato suggested that VqSTS36 played
      a specific role in different phytohormone-related pathways, including salicylic
      acid, jasmonic acid, and abscisic acid signaling pathways. All of these results
      provided a better understanding of the mechanism behind the role of VqSTS36 in
      biotic and abiotic stress.

PMID- 30274343
TI  - New Layered Polythiophene-Silica Composite Through the Self-Assembly and
      Polymerization of Thiophene-Based Silylated Molecular Precursors.
AB  - A new layered hybrid polythiophene-silica material was obtained directly by
      hydrolysis and polycondensation (sol-gel) of a silylated-thiophene bifunctional
      precursor, and its subsequent oxidative polymerization by FeCl3. This precursor
      was judiciously designed to guarantee its self-assembly and the formation of a
      lamellar polymer-silica structure, exploiting the cooperative effect between the
      hydrogen bonding interactions, originating from the ureido groups and the pi
      stacking interactions between the thiophene units. The lamellar structure of the
      polythiophene-silica composite was confirmed by X-ray powder diffraction (XRD)
      and transmission electron microscopy (TEM) analyses. The solid-state nuclear
      magnetic resonance (NMR), UV-Vis, and photoluminescence spectra unambiguously
      indicate the incorporation of polythiophene into the silica matrix. Our work
      demonstrates that using a polymerizable silylated-thiophene precursor is an
      efficient approach towards the formation of nanostructured conjugated polymer
      based hybrid materials.

PMID- 30274345
TI  - Formation of alpha- and beta-Cembratriene-Diols in Tobacco (Nicotiana tabacum L.)
      Is Regulated by Jasmonate-Signaling Components via Manipulating Multiple
      Cembranoid Synthetic Genes.
AB  - Cembranoids are a group of natural diterpenoid compounds with pharmaceutical
      potentials, and the cembratriene-diols produced by Nicotiana (tobacco) species
      display activities in anti-nicotine addiction and neuron protection. Although the
      enzymes catalyzing cembratriene-diols' formation in tobacco have been
      investigated, the regulatory mechanism underlying this physiological process
      remains unknown. This study has investigated the roles of phytohormone jasmonic
      acid (JA) in regulating cembratriene-diol formation in N. tabacum cv. TN90 and
      found that JA and COI1, the receptor protein of the bioactive derivative of JA
      (i.e., JA-Ile), display critical roles in regulating cembratriene-diols'
      formation and the expression of cembranoid synthetic genes CBTS, P450 and NtLTP1.
      Further studies showed that over-expressing either the gene encoding bHLH
      transcription factor MYC2a or that encoding MYB transcription factor MYB305 could
      upregulate the cembranoid synthetic genes and enhance the cembranoid production
      in plants with dysfunction of COI1. Further studies suggest that COI1 and its
      downstream regulators MYC2a and MYB305 also modulate the trichome secretion,
      which is correlated with cembranoid formation. Taken together, this study has
      demonstrated a critical role of JA-signaling components in governing the
      cembratriene-diol formation and the transcription of cembratriene-diol synthetic
      genes in tobacco. Findings in this study are of great importance to reveal the
      molecular regulatory mechanism underlying cembranoid synthesis.

PMID- 30274344
TI  - A Comparison of a Pulse-Based Diet and the Therapeutic Lifestyle Changes Diet in
      Combination with Exercise and Health Counselling on the Cardio-Metabolic Risk
      Profile in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial.
AB  - : We compared the effects of a low-glycemic index pulse-based diet, containing
      lentils, beans, split peas, and chickpeas, to the Therapeutic Lifestyle Changes
      (TLC) diet on cardio-metabolic measures in women with polycystic ovary syndrome
      (PCOS). Ninety-five women (18-35 years) enrolled in a 16-week intervention; 30
      women in the pulse-based and 31 in the TLC groups completed the study. Women
      participated in aerobic exercise training (minimum 5 days/week for 45 min/day)
      and were counselled (monthly) about PCOS and lifestyle modification. Women
      underwent longitudinal follow-up post-intervention. The pulse-based group had a
      greater reduction in total area under the curve for insulin response to a 75-g
      oral glucose tolerance test (mean change +/- SD: -121.0 +/- 229.9 vs. -27.4 +/-
      110.2 uIU/mL * min; p = 0.05); diastolic blood pressure (-3.6 +/- 6.7 vs. -0.2 +/
      6.7 mmHg, p = 0.05); triglyceride (-0.2 +/- 0.6 vs. 0.0 +/- 0.5 mmol/L, p =
      0.04); low-density lipoprotein cholesterol (-0.2 +/- 0.4 vs. -0.1 +/- 0.4 mmol/L,
      p = 0.05); total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C; -0.4
      +/- 0.4 vs. 0.1 +/- 0.4, p < 0.001); and a greater increase in HDL-C (0.1 +/- 0.2
      vs. -0.1 +/- 0.2 mmol/L, p < 0.01) than the TLC group. Decreased TC/HDL-C (p =
      0.02) at six-month and increased HDL-C and decreased TC/HDL-C (p <= 0.02) at 12
      month post-intervention were maintained in the pulse-based group. A pulse-based
      diet may be more effective than the TLC diet at improving cardio-metabolic
      disease risk factors in women with PCOS. TRIAL REGISTRATION: CinicalTrials.gov
      identifier, NCT01288638.

PMID- 30274347
TI  - Wasabia koreana Nakai: A Preliminary Study on Nutrients and Chemical Compounds
      That May Impact Sensory Properties.
AB  - In this study, the nutritional, functional, and chemical measurements of sensory
      attributes of different parts of wasabi, namely, leaf, petiole, and rhizome, were
      investigated. Proximate composition analysis showed the presence of high amounts
      of carbohydrates in the rhizome and amino acid composition analysis confirmed
      high proportions of glutamic acid and aspartic acid in all three parts. While
      proximate composition showed low lipid content in wasabi, omega-3 fatty acids
      accounted for a high proportion (>44%) of the total lipids. Wasabi leaves had
      high vitamin C and total phenolic contents, and thus demonstrated antioxidant
      capacity. Allyl isothiocyanate, which gives wasabi its characteristic pungent
      taste, was identified by gas chromatography/mass spectrometry and an electronic
      nose. On an electronic tongue, wasabi leaves showed compounds associated with
      sourness and saltiness while the petiole had high content of compounds associated
      with sweetness and bitterness. This study provides basic data for the utilization
      of wasabi parts as food materials based on their nutritional, functional, and
      chemical measure of sensory attributes.

PMID- 30274346
TI  - LP1 from Lentinula edodes C91-3 Induces Autophagy, Apoptosis and Reduces
      Metastasis in Human Gastric Cancer Cell Line SGC-7901.
AB  - Present study aimed to elucidate the anticancer effect and the possible molecular
      mechanism underlying the action of Latcripin 1 (LP1), from the mushroom Lentinula
      edodes strain C91-3 against gastric cancer cell lines SGC-7901 and BGC-823. Cell
      viability was measured by Cell Counting Kit-8 (CCK-8); morphological changes were
      observed by phase contrast microscope; autophagy was determined by transmission
      electron microscope and fluorescence microscope. Apoptosis and cell cycle were
      assessed by flow cytometer; wound-healing, transwell migration and invasion
      assays were performed to investigate the effect of LP1 on gastric cancer cell's
      migration and invasion. Herein, we found that LP1 resulted in the induction of
      autophagy by the formation of autophagosomes and conversion of light chain 3
      (LC3I into LC3II. LP1 up-regulated the expression level of autophagy-related gene
      (Atg7, Atg5, Atg12, Atg14) and Beclin1; increased and decreased the expression
      level of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins respectively,
      along with the activation of Caspase-3. At lower-doses, LP1 have shown to arrest
      cells in the S phase of the cell cycle and decreased the expression level of
      matrix metalloproteinase MMP-2 and MMP-9. In addition, it has also been shown to
      regulate the phosphorylation of one of the most hampered gastric cancer pathway,
      that is, protein kinase B/mammalian target of rapamycin (Akt/mTOR) channel and
      resulted in cell death. These findings suggested LP1 as a potential natural anti
      cancer agent, for exploring the gastric cancer therapies and as a contender for
      further in vitro and in vivo investigations.

PMID- 30274348
TI  - A Quantum-Based Microwave Magnetic Field Sensor.
AB  - In this paper, a quantum-based method for measuring the microwave magnetic field
      in free space is presented by exploring atomic Rabi resonance in the clock
      transition of 133Cs. A compact cesium glass cell serving as the microwave
      magnetic field sensing head was used to measure the spatial distribution of
      microwave radiation from an open-ended waveguide antenna. The measured microwave
      magnetic field was not restricted by other microwave devices. The longitudinal
      distribution of the magnetic field was measured. The experimental results
      measured by the sensor were in agreement with the simulation. In addition, a
      slightly electromagnetic perturbation caused by the glass cell was investigated
      through simulation calculations.

PMID- 30274349
TI  - Seafarers' Quality of Life: Organizational Culture, Self-Efficacy, and Perceived
      Fatigue.
AB  - Using the Culture-Work-Health model, this study investigates the factors
      influencing the quality of life of seafarers. This study conducted a survey of
      320 seafarers who have lived and worked on a ship for more than six months. This
      self-administered questionnaire included questions on organizational culture and
      support, self-efficacy, perceived fatigue, as well as the quality of work life.
      Organizational culture and self-efficacy were identified as factors affecting the
      quality of work life, while organizational support was found to have an indirect
      effect through self-efficacy and perceived fatigue. The final model accounts for
      63.1% of the variance in seafarers' quality of life. As such, this study shows
      that self-efficacy is important for the quality of life of seafarers, having both
      direct and indirect effects. Moreover, organizational support may prove to be the
      primary intervention point for relieving perceived fatigue and enhancing self
      efficacy, thus improving the quality of work life.

PMID- 30274351
TI  - Respiratory Syncytial Virus Matrix (M) Protein Interacts with Actin In Vitro and
      in Cell Culture.
AB  - The virus-host protein interactions that underlie respiratory syncytial virus
      (RSV) assembly are still not completely defined, despite almost 60 years of
      research. RSV buds from the apical surface of infected cells, once virion
      components have been transported to the budding sites. Association of RSV matrix
      (M) protein with the actin cytoskeleton may play a role in facilitating this
      transport. We have investigated the interaction of M with actin in vitro and cell
      culture. Purified wildtype RSV M protein was found to bind directly to
      polymerized actin in vitro. Vero cells were transfected to express full-length M
      (1-256) as a green fluorescent protein-(GFP) tagged protein, followed by
      treatment with the microfilament destabilizer, cytochalasin D. Destabilization of
      the microfilament network resulted in mislocalization of full-length M, from
      mostly cytoplasmic to diffused across both cytoplasm and nucleus, suggesting that
      M interacts with microfilaments in this system. Importantly, treatment of RSV
      infected cells with cytochalasin D results in lower infectious virus titers, as
      well as mislocalization of M to the nucleus. Finally, using deletion mutants of M
      in a transfected cell system, we show that both the N- and C-terminus of the
      protein are required for the interaction. Together, our data suggest a possible
      role for M-actin interaction in transporting virion components in the infected
      cell.

PMID- 30274352
TI  - A Prediction-Based Spatial-Spectral Adaptive Hyperspectral Compressive Sensing
      Algorithm.
AB  - In order to improve the performance of storage and transmission of massive
      hyperspectral data, a prediction-based spatial-spectral adaptive hyperspectral
      compressive sensing (PSSAHCS) algorithm is proposed. Firstly, the spatial block
      size of hyperspectral images is adaptively obtained according to the spatial self
      correlation coefficient. Secondly, a k-means clustering algorithm is used to
      group the hyperspectral images. Thirdly, we use a local means and local standard
      deviations (LMLSD) algorithm to find the optimal image in the group as the key
      band, and the non-key bands in the group can be smoothed by linear prediction.
      Fourthly, the random Gaussian measurement matrix is used as the sampling matrix,
      and the discrete cosine transform (DCT) matrix serves as the sparse basis.
      Finally, the stagewise orthogonal matching pursuit (StOMP) is used to reconstruct
      the hyperspectral images. The experimental results show that the proposed PSSAHCS
      algorithm can achieve better evaluation results-the subjective evaluation, the
      peak signal-to-noise ratio, and the spatial autocorrelation coefficient in the
      spatial domain, and spectral curve comparison and correlation between spectra
      reconstructed performance in the spectral domain-than those of single spectral
      compression sensing (SSCS), block hyperspectral compressive sensing (BHCS), and
      adaptive grouping distributed compressive sensing (AGDCS). PSSAHCS can not only
      compress and reconstruct hyperspectral images effectively, but also has strong
      denoise performance.

PMID- 30274350
TI  - Field Propagation Experiments of Male African Savanna Elephant Rumbles: A Focus
      on the Transmission of Formant Frequencies.
AB  - African savanna elephants live in dynamic fission-fusion societies and exhibit a
      sophisticated vocal communication system. Their most frequent call-type is the
      'rumble', with a fundamental frequency (which refers to the lowest vocal fold
      vibration rate when producing a vocalization) near or in the infrasonic range.
      Rumbles are used in a wide variety of behavioral contexts, for short- and long
      distance communication, and convey contextual and physical information. For
      example, maturity (age and size) is encoded in male rumbles by formant
      frequencies (the resonance frequencies of the vocal tract), having the most
      informative power. As sound propagates, however, its spectral and temporal
      structures degrade progressively. Our study used manipulated and resynthesized
      male social rumbles to simulate large and small individuals (based on different
      formant values) to quantify whether this phenotypic information efficiently
      transmits over long distances. To examine transmission efficiency and the
      potential influences of ecological factors, we broadcasted and re-recorded
      rumbles at distances of up to 1.5 km in two different habitats at the Addo
      Elephant National Park, South Africa. Our results show that rumbles were affected
      by spectral-temporal degradation over distance. Interestingly and unlike previous
      findings, the transmission of formants was better than that of the fundamental
      frequency. Our findings demonstrate the importance of formant frequencies for the
      efficiency of rumble propagation and the transmission of information content in a
      savanna elephant's natural habitat.

PMID- 30274353
TI  - Screening of Ulva rigida, Gracilaria sp., Fucus vesiculosus and Saccharina
      latissima as Functional Ingredients.
AB  - The intent of the present work was to evaluate the potential of four macroalgae
      prevalent in Europe, namely Ulva rigida, Gracilaria sp., Fucus vesiculosus and
      Saccharina latissima, for application in functional foods, either in the direct
      form or as extracts. Accordingly, nutritional composition, the content of
      phytochemical antioxidants, and the inhibitory ability of key enzymes with
      impacts on obesity and diabetes (alpha-glucosidase and pancreatic lipase) or on
      arterial pressure (angiotensin-I converting enzyme), were evaluated. Overall,
      protein, lipid, ash and fiber contents of the macroalgae ranged from 9-24% dw,
      0.5-3.0% dw, 20-32% dw, and 37-45% dw, respectively, making them good candidates
      for nutritional supplementation of several foods, particularly due to their
      mineral and fiber contents. In addition, brown macroalgae, in particular F.
      vesiculosus, stood out for its superior phenolic content, which was reflected by
      its high antioxidant ability and inhibition towards alpha-glucosidase activity
      (0.032 mg/mL of hydroacetonic extract inhibited 50% of the enzyme activity).

PMID- 30274354
TI  - Anemia and Iron Deficiency in Cancer Patients: Role of Iron Replacement Therapy.
AB  - Anemia in cancer patients is quite common, with remarkable negative impacts on
      quality of life and overall prognosis. The pathogenesis is complex and typically
      multifactorial, with iron deficiency (ID) often being a major and potentially
      treatable contributor. In turn, ID in cancer patients can be due to multiple
      concurring mechanisms, including bleeding (e.g., in gastrointestinal cancers or
      after surgery), malnutrition, medications, and hepcidin-driven iron sequestration
      into macrophages with subsequent iron-restricted erythropoiesis. Indeed, either
      absolute or functional iron deficiency (AID or FID) can occur. While for absolute
      ID there is a general consensus regarding the laboratory definition (that is
      ferritin levels <100 ng/mL +/- transferrin saturation (TSAT) <20%), a shared
      definition of functional ID is still lacking. Current therapeutic options in
      cancer anemia include iron replacement, erythropoietic stimulating agents (ESAs),
      and blood transfusions. The latter should be kept to a minimum, because of
      concerns regarding risks, costs, and limited resources. Iron therapy has proved
      to be a valid approach to enhance efficacy of ESAs and to reduce transfusion
      need. Available guidelines focus mainly on patients with chemotherapy-associated
      anemia, and generally suggest intravenous (IV) iron when AID or FID is present.
      However, in the case of FID, the upper limit of ferritin in association with TSAT
      <20% at which iron should be prescribed is a matter of controversy, ranging up to
      800 ng/mL. An increasingly recognized indication to IV iron in cancer patients is
      represented by preoperative anemia in elective oncologic surgery. In this
      setting, the primary goal of treatment is to decrease the need of blood
      transfusions in the perioperative period, rather than improving anemia-related
      symptoms as in chemotherapy-associated anemia. Protocols are mainly based on
      experiences of Patient Blood Management (PBM) in non-oncologic surgery, but no
      specific guidelines are available for oncologic surgery. Here we discuss some
      possible approaches to the management of ID in cancer patients in different
      clinical settings, based on current guidelines and recommendations, emphasizing
      the need for further research in the field.

PMID- 30274355
TI  - Prevention of Progression in Myopia: A Systematic Review.
AB  - The prevalence of myopia has increased worldwide in recent decades and now is
      endemic over the entire industrial world. This increase is mainly caused by
      changes in lifestyle and behavior. In particular, the amount of outdoor
      activities and near work would display an important role in the pathogenesis of
      the disease. Several strategies have been reported as effective. Spectacles and
      contact lenses have shown only slight results in the prevention of myopia and
      similarly ortokerathology should not be considered as a first-line strategy,
      given the high risk of infectious keratitis and the relatively low compliance for
      the patients. Thus, to date, atropine ophthalmic drops seem to be the most
      effective treatment for slowing the progression of myopia, although the exact
      mechanism of the effect of treatment is still uncertain. In particular, low-dose
      atropine (0.01%) was proven to be an effective and safe treatment in the long
      term due to the lowest rebound effect with negligible side effects.

PMID- 30274356
TI  - In Situ Investigation of Grain Evolution of 300M Steel in Isothermal Holding
      Process.
AB  - The relationships between initial microstructures, process parameters, and grain
      evolutions in isothermal holdings have drawn wide attention in recent years, but
      the grain growth behaviors of 300M steel were not well understood, resulting in a
      failure in precise microstructure controlling in heat treatment. In this work, in
      situ observations were carried out to characterize the grain evolutions of 300M
      steel with varying holding time, holding temperatures, and initial
      microstructures. The intriguing finding was that the grain refinement by
      austenization of 300M steel was followed by a dramatic grain growth in the
      initial stage of holding (<=~600 s), and with increasing time (~600-7200 s), the
      average grain size appeared to have a limit value at specific temperatures. The
      austenization process accelerated the grain growth by generating large quantity
      of grain boundaries at the initial stage of holdings, and the growth rate
      gradually slowed down after holding for ~600 s because the driven force was
      weakened due to the reduction of grain boundary energy. The initial structure and
      the initial grain size of 300M steel had no obvious influences on the grain size
      evolutions. The mechanisms of grain growth were analyzed based on in situ
      observations and transmission electron microscope (TEM) characterizations. A
      grain evolution model considering the grain boundary migration of 300M steel was
      established for the isothermal holding process. Good agreement was obtained
      between the in situ observation results and the model calculation results. This
      investigation aimed to understand fundamentally the grain evolutions of 300M
      steel in the isothermal holding process.

PMID- 30274357
TI  - Immunogenicity and Protective Activity of a Chimeric Protein Based on the Domain
      III of the Tick-Borne Encephalitis Virus E Protein and the OmpF Porin of Yersinia
      pseudotuberculosis Incorporated into the TI-Complex.
AB  - Tick-borne encephalitis (TBE) is a widespread, dangerous infection.
      Unfortunately, all attempts to create safe anti-TBE subunit vaccines are still
      unsuccessful due to their low immunogenicity. The goal of the present work was to
      investigate the immunogenicity of a recombinant chimeric protein created by the
      fusion of the EIII protein, comprising domain III and a stem region of the tick
      borne encephalitis virus (TBEV) E protein, and the OmpF porin of Yersinia
      pseudotuberculosis (OmpF-EIII). Adjuvanted antigen delivery systems, the tubular
      immunostimulating complexes (TI-complexes) based on the
      monogalactosyldiacylglycerol from different marine macrophytes, were used to
      enhance the immunogenicity of OmpF-EIII. Also, the chimeric protein incorporated
      into the most effective TI-complex was used to study its protective activity. The
      content of anti-OmpF-EIII antibodies was estimated in mice blood serum by enzyme
      linked immunosorbent assay (ELISA). To study protective activity, previously
      immunized mice were infected with TBEV strain Dal'negorsk (GenBank ID: FJ402886).
      The animal survival was monitored daily for 21 days. OmpF-EIII incorporated into
      the TI-complexes induced about a 30-60- and 5-10-fold increase in the production
      of anti-OmpF-EIII and anti-EIII antibodies, respectively, in comparison with the
      effect of an individual OmpF-EIII. The most effective vaccine construction
      provided 60% protection. Despite the dramatic effect on the specific antibody
      titer, the studied TI-complex did not provide a statistically significant
      increase in the protection of OmpF-EIII protein. However, our results provide the
      basis of the future search for approaches to design and optimize the anti-TBEV
      vaccine based on the OmpF-EIII protein.

PMID- 30274358
TI  - Optimization of Ultrasound-Assisted Extraction of Flavonoids from Olive (Olea
      europaea) Leaves, and Evaluation of Their Antioxidant and Anticancer Activities.
AB  - Olea europaea leaves are the major byproduct of olive farming. In this study,
      ultrasound-assisted extraction of flavonoids from olive leaves was optimized
      using response surface methodology, and the flavonoid compounds and their
      antioxidant and anticancer activities were investigated by high performance
      liquid chromatography. The results showed that the optimized conditions for
      achieving the maximum yield of flavonoids (74.95 mg RE/g dm) were 50  degrees C
      temperature, 270 W power, 50 min time, and 41 mL/g liquid-solid ratio. There was
      a significant difference in the total flavonoid content between the aged and
      young leaves harvested in April and July, and six main components were
      quantified. Among them, luteolin-4'-O-glucoside was the most predominant
      flavonoid compound, followed by apigenin-7-O-glucoside and rutin. Olive leaves
      also contained small amounts of luteolin, apigenin, and quercetin. Additionally,
      excellent antioxidant activity was exhibited when tested with the DPPH assay;
      superoxide radical-scavenging ability and reducing power was also tested. The
      anticancer activity of the flavonoids was assessed using HeLa cervical cancer
      cells, and it was observed that increasing concentrations of olive leaf
      flavonoids resulted in decreased cancer cell viability. These results suggest
      that the flavonoids from olive leaves could be used as a potential source of
      natural antioxidants for the pharmaceutical and food industries.

PMID- 30274359
TI  - Supplementation of Short-Chain Fatty Acid, Sodium Propionate, in Patients on
      Maintenance Hemodialysis: Beneficial Effects on Inflammatory Parameters and Gut
      Derived Uremic Toxins, A Pilot Study (PLAN Study)
AB  - BACKGROUND: In end-stage renal disease (ESRD), gut-derived uremic toxins play a
      crucial role in the systemic inflammation and oxidative stress promoting the
      excess morbidity and mortality. The biochemical derangement is in part a
      consequence of an insufficient generation of short-chain fatty acids (SCFA) due
      to the dysbiosis of the gut and an insufficient consumption of the fermentable
      complex carbohydrates. AIM OF THE STUDY: The primary end-point was to evaluate
      the potential efficacy of SCFA (specifically, sodium propionate (SP)) for
      patients on maintenance hemodialysis (MHD) on systemic inflammation. Secondary
      end-points included potential attenuation of oxidative stress markers, insulin
      resistance and production of gut-derived uremic toxins indoxyl sulfate and p
      cresol sulfate, as well as health status after SP supplementation. STUDY DESIGN:
      We performed a single-center non-randomized pilot study in 20 MHD patients. They
      received the food additive SP with a daily intake of 2 * 500 mg in the form of
      capsules for 12 weeks. Pre-dialysis blood samples were taken at the beginning,
      after six weeks and at the end of the administration period, as well as four
      weeks after withdrawal of the treatment. RESULTS: The subjects revealed a
      significant decline of inflammatory parameters C-reactive protein (-46%),
      interleukin IL-2 (-27%) and IL-17 (-15%). The inflammatory parameters IL-6 and
      IFN-gamma showed a mild non-significant reduction and the anti-inflammatory
      cytokine IL-10 increased significantly (+71%). While the concentration of
      bacterial endotoxins and TNF-alpha remained unchanged, the gut-derived uremic
      toxins, indoxyl sulfate (-30%) and p-cresyl sulfate (-50%), revealed a
      significant decline. The SP supplementation reduced the parameters of oxidative
      stress malondialdehyde (-32%) and glutathione peroxidase activity (-28%). The
      serum insulin levels dropped by 30% and the HOMA-index by 32%. The reduction of
      inflammatory parameters was associated with a lowering of ferritin and a
      significant increase in transferrin saturation (TSAT). Four weeks after the end
      of the treatment phase, all improved parameters deteriorated again. Evaluation of
      the psycho-physical performance with the short form 36 (SF-36) questionnaire
      showed an enhancement in the self-reported physical functioning, general health,
      vitality and mental health. The SP supplementation was well tolerated and without
      important side effects. No patient had left the study due to intolerance to the
      medication. The SP supplementation in MHD patients reduced pro-inflammatory
      parameters and oxidative stress and improved insulin resistance and iron
      metabolism. Furthermore, SP effectively lowered the important gut-derived uremic
      toxins indoxyl and p-cresol sulfate. These improvements were associated with a
      better quality of life. Further controlled studies are required in a larger
      cohort to evaluate the clinical outcome.

PMID- 30274360
TI  - Analysis of "2.28" KEEPER Chemical Industries Hazardous Chemical Explosion
      Accident Based on FTA and HFACS.
AB  - On 28 February 2012, a guanidine nitrate explosion occurred at HEBEI KEEPER
      Chemical Industries Co., Ltd., China, resulting in 25 deaths, with 4 missing
      individuals and 46 injured. In order to explore the causal relationship hidden
      behind this accident, fault tree analysis (FTA) and the Human Factors Analysis
      and Classification System (HFACS) were used to systematically analyze the
      incident. Firstly, FTA was used to analyze the causes of the accident in depth,
      until all the basic causal events causing the guanidine nitrate explosion were
      identified, and a fault tree diagram of the guanidine nitrate explosion was
      drawn. Secondly, for the unsafe acts in the basic causal events, the HFACS model
      was used to analyze the three levels of factors that lead to unsafe acts,
      including the preconditions for unsafe acts, unsafe supervision, and
      organizational influences. Finally, based on the analysis results of FTA and
      HFACS, a complete logic diagram of the causes of the accident was obtained. The
      FTA and HFACS accident analysis methods allowed for the identification of human
      factors and the accident evolution process in the explosion accident and provide
      a reference for accident investigation.

PMID- 30274361
TI  - Identification of a cis-Acting Element Derived from Tomato Leaf Curl Yunnan Virus
      that Mediates the Replication of a Deficient Yeast Plasmid in Saccharomyces
      cerevisiae.
AB  - Geminiviruses are a group of small single-stranded DNA viruses that replicate in
      the host cell nucleus. It has been reported that the viral replication initiator
      protein (Rep) and the conserved common region (CR) are required for rolling
      circle replication (RCR)-dependent geminivirus replication, but the detailed
      mechanisms of geminivirus replication are still obscure owing to a lack of a
      eukaryotic model system. In this study, we constructed a bacterial-yeast shuttle
      plasmid with the autonomous replication sequence (ARS) deleted, which failed to
      replicate in Saccharomyces cerevisiae cells and could not survive in selective
      media either. Tandemly repeated copies of 10 geminivirus genomic DNAs were
      inserted into this deficient plasmid to test whether they were able to replace
      the ARS to execute genomic DNA replication in yeast cells. We found that yeast
      cells consisting of the recombinant plasmid with 1.9 tandemly repeated copies of
      tomato leaf curl Yunnan virus isolate Y194 (TLCYnV-Y194, hereafter referred to as
      Y194) can replicate well and survive in selective plates. Furthermore, we showed
      that the recombinant plasmid harboring the Y194 genome with the mutation of the
      viral Rep or CR was still able to replicate in yeast cells, indicating the
      existence of a non-canonic RCR model. By a series of mutations, we mapped a short
      fragment of 174 nucleotides (nts) between the V1 and C3 open reading frames
      (ORFs), including an ARS-like element that can substitute the function of the ARS
      responsible for stable replication of extrachromosomal DNAs in yeast. The results
      of this study established a geminivirus replication system in yeast cells and
      revealed that Y194 consisting of an ARS-like element was able to support the
      replication a bacterial-yeast shuttle plasmid in yeast cells.

PMID- 30274362
TI  - Integrating Early Growth Information to Monitor Winter Wheat Powdery Mildew Using
      Multi-Temporal Landsat-8 Imagery.
AB  - Powdery mildew is one of the dominant diseases in winter wheat. The accurate
      monitoring of powdery mildew is important for crop management and production.
      Satellite-based remote sensing monitoring has been proven as an efficient tool
      for regional disease detection and monitoring. However, the information provided
      by single-date satellite scene is hard to achieve acceptable accuracy for powdery
      mildew disease, and incorporation of early period contextual information of
      winter wheat can improve this situation. In this study, a multi-temporal
      satellite data based powdery mildew detecting approach had been developed for
      regional disease mapping. Firstly, the Lansat-8 scenes that covered six winter
      wheat growth periods (expressed in chronological order as periods 1 to 6) were
      collected to calculate typical vegetation indices (VIs), which include disease
      water stress index (DSWI), optimized soil adjusted vegetation index (OSAVI),
      shortwave infrared water stress index (SIWSI), and triangular vegetation index
      (TVI). A multi-temporal VIs-based k-nearest neighbors (KNN) approach was then
      developed to produce the regional disease distribution. Meanwhile, a backward
      stepwise elimination method was used to confirm the optimal multi-temporal
      combination for KNN monitoring model. A classification and regression tree (CART)
      and back propagation neural networks (BPNN) approaches were used for comparison
      and validation of initial results. VIs of all periods except 1 and 3 provided the
      best multi-temporal data set for winter wheat powdery mildew monitoring. Compared
      with the traditional single-date (period 6) image, the multi-temporal images
      based KNN approach provided more disease information during the disease
      development, and had an accuracy of 84.6%. Meanwhile, the accuracy of the
      proposed approach had 11.5% and 3.8% higher than the multi-temporal images-based
      CART and BPNN models', respectively. These results suggest that the use of
      satellite images for early critical disease infection periods is essential for
      improving the accuracy of monitoring models. Additionally, satellite imagery also
      assists in monitoring powdery mildew in late wheat growth periods.

PMID- 30274363
TI  - Dominant Role of Young's Modulus for Electric Power Generation in PVDF-BaTiO3
      Composite-Based Piezoelectric Nanogenerator.
AB  - The electric power output of a piezoelectric nanogenerator (PENG) depends on the
      various physical parameters of the constituent materials, including the
      piezoelectric coefficient, Young's modulus, and dielectric constant. Herein, we
      report the mechanical and electrical properties of a poly(vinylidene fluoride)
      BaTiO3 (PVDF-BTO) composite-based PENG. Variation of the BTO nanoparticle (NP)
      content enabled the systematic tuning of the physical parameters that are related
      to power generation in the composite. The Young's modulus of the PVDF-BTO
      composite initially increased, and then eventually decreased, with the increasing
      BTO content, which was probably due to the clustering effect of the high modulus
      BTO NPs. The dielectric constant of the composite continuously increased as the
      BaTiO3 content increased. The piezoelectric outputs were greatly enhanced at 10
      wt% of BTO, where the Young's modulus was the highest. These results indicate
      that the Young's modulus plays an important role in the piezoelectric power
      generation of the composite-based PENGs.

PMID- 30274364
TI  - Potential Role of Microfibrillar-Associated Protein 4, Fibrotic Indices and
      Oxidative Stress in Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related
      mortality worldwide. In an attempt to understand some potential mechanisms of
      persistence and oncogenicity of Hepatitis C virus (HCV)-related HCC,
      microfibrillar-associated protein 4 (MFAP4), fibrotic indices and oxidative
      status biomarkers were assessed in the sera of 50 patients with HCV-associated
      HCC, 25 patients with HCV-related liver cirrhosis and 15 healthy individuals.
      Serum oxidized Coenzyme Q10 (CoQ10) and malondialdehyde showed significant
      elevation in HCC patients compared to the control group (p < 0.001), as well as
      cirrhotic patients (p < 0.05 and p < 0.001, respectively), while serum
      glutathione content and superoxide dismutase activity were significantly
      decreased in HCC patients compared to the control group (p < 0.001). Serum MFAP4,
      aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based
      on the 4 factors (FIB-4) and Forns index showed significant increase in HCC
      patients compared to the control group (p < 0.001), while only APRI and FIB-4
      were significantly different between HCC and cirrhotic patients (p < 0.05), with
      a sensitivity of 86% and 92%, respectively, at cut off >=0.7 for APRI and >=1.57
      for FIB-4. Therefore, increasing oxidative stress and fibrosis might mediate HCV
      induced cirrhosis and HCC. APRI and FIB-4 may be used as a simple non-expensive
      formula for the screening of HCC rather than MFAP4.

PMID- 30274366
TI  - Directed Evolution of a Homodimeric Laccase from Cerrena unicolor BBP6 by Random
      Mutagenesis and In Vivo Assembly.
AB  - Laccases have great potential for industrial applications due to their green
      catalytic properties and broad substrate specificities, and various studies have
      attempted to improve the catalytic performance of these enzymes. Here, to the
      best of our knowledge, we firstly report the directed evolution of a homodimeric
      laccase from Cerrena unicolor BBP6 fused with alpha-factor prepro-leader that was
      engineered through random mutagenesis followed by in vivo assembly in
      Saccharomyces cerevisiae. Three evolved fusion variants selected from ~3500
      clones presented 31- to 37-fold increases in total laccase activity, with better
      thermostability and broader pH profiles. The evolved alpha-factor prepro-leader
      enhanced laccase expression levels by up to 2.4-fold. Protein model analysis of
      these variants reveals that the beneficial mutations have influences on protein
      pKa shift, subunit interaction, substrate entrance, and C-terminal function.

PMID- 30274365
TI  - Short Telomere Length as a Biomarker Risk of Lung Cancer Development Induced by
      High Radon Levels: A Pilot Study.
AB  - Long-term exposure to radon has been determined to be the second leading cause of
      lung cancer after tobacco smoking. However, an in-depth study of this topic has
      not been explicitly carried out in Chiang Mai (Thailand). This paper presents the
      results of an indoor radon level measurement campaign in dwellings of Chiang Mai
      using total of 110 detectors (CR-39) during one year. The results show that the
      average radon levels varied from 35 to 219 Bq/m3, with an overall average of 57
      Bq/m3. The finding also shows that the average value is higher than the global
      average value of 39 Bq/m3. In addition, to examine the cause of lung cancer
      development among people with risk of chronic exposure to radon during their
      lifetime, 35 non-smoker lung cancer patients and 33 healthy nonsmokers were
      analyzed for telomere length. As expected, telomere length was significantly
      shorter in lung cancer patients than in healthy nonsmokers. Among healthy
      nonsmokers, the telomere length was significantly shorter in a high radon group
      than in an unaffected low radon group. To the best of our knowledge, our research
      provides the first attempt in describing the shortened telomeres in areas with
      high levels of environmental radon that might be related to lung cancer
      development.

PMID- 30274367
TI  - Quasicontinuum Simulation of the Effect of Lotus-Type Nanocavity on the Onset
      Plasticity of Single Crystal Al during Nanoindentation.
AB  - Stress concentration around nanosized defects such as cavities always leads to
      plastic deformation and failure of solids. We investigate the effects of depth,
      size, and shape of a lotus-type nanocavity on onset plasticity of single crystal
      Al during nanoindentation on a (001) surface using a quasicontinuum method. The
      results show that the presence of a nanocavity can greatly affect the contact
      stiffness (Sc) and yield stress (sigmay) of the matrix during nanoindentation.
      For a circular cavity, the Sc and sigmay gradually increase with the cavity
      depth. A critical depth can be identified, over which the Sc and sigmay are
      insensitive to the cavity depth and it is firstly observed that the nucleated
      dislocations extend into the matrix and form a y-shaped structure. Moreover, the
      critical depth varies approximately linearly with the indenter size, regarding
      the same cavity. The Sc almost linearly decreases with the cavity diameter, while
      the sigmay is slightly affected. For an ellipsoidal cavity, the Sc and sigmay
      increase with the aspect ratio (AR), while they are less affected when the AR is
      over 1. Our results shed light in the mechanical behavior of metals with cavities
      and could also be helpful in designing porous materials and structures.

PMID- 30274369
TI  - A Framework for Development of Useful Metabolomic Biomarkers and Their Effective
      Knowledge Translation.
AB  - Despite the significant advantages of metabolomic biomarkers, no diagnostic tests
      based on metabolomics have been introduced to clinical use. There are many
      reasons for this, centered around substantial obstacles in developing clinically
      useful metabolomic biomarkers. Most significant is the need for interdisciplinary
      teams with expertise in metabolomics, analysis of complex clinical and
      metabolomic data, and clinical care. Importantly, the clinical need must precede
      biomarker discovery, and the experimental design for discovery and validation
      must reflect the purpose of the biomarker. Standard operating procedures for
      procuring and handling samples must be developed from the beginning, to ensure
      experimental integrity. Assay design is another challenge, as there is not much
      precedent informing this. Another obstacle is that it is not yet clear how to
      protect any intellectual property related to metabolomic biomarkers. Viewing a
      metabolomic biomarker as a natural phenomenon would inhibit patent protection and
      potentially stifle commercial interest. However, demonstrating that a metabolomic
      biomarker is actually a derivative of a natural phenomenon that requires
      innovation would enhance investment in this field. Finally, effective knowledge
      translation strategies must be implemented, which will require engagement with
      end users (clinicians and lab physicians), patient advocate groups, policy
      makers, and payer organizations. Addressing each of these issues comprises the
      framework for introducing a metabolomic biomarker to practice.

PMID- 30274368
TI  - Children's Blood Lead Concentrations from 1988 to 2015 in Mexico City: The
      Contribution of Lead in Air and Traditional Lead-Glazed Ceramics.
AB  - Despite the removal of lead from gasoline in 1997, elevated blood lead levels
      (BLLs) > 5 ug/dL are still detectable in children living in Mexico City. The use
      of lead-glazed ceramics may explain these persistent exposure levels. Mexico
      lacks a national surveillance program for BLL, but temporal trends can be derived
      from epidemiological studies. With this approach, we leveraged a series of birth
      cohorts to report BLL trends from 1987 to 2002 and expanded our analysis to 2015.
      Data were from 1-5-year-old children from five Mexico City cohorts followed
      between 1988 and 2015. BLLs are reported on 1963 children, who contributed 4975
      BLLs. We estimated the trend of mean BLL, which decreased from 15.7 ug/dL in
      1988, to 7.8 ug/dL in 1998 (a year after the total ban of lead in gasoline), to
      1.96 ug/dL in 2015. The proportion of BLL >= 5 ug/dL decreased from 92% (1988
      1998) to 8% (2008-2015). The use of lead-glazed ceramics was associated with an
      11% increase in BLLs throughout the study period. Replacing lead-based glazes in
      traditional ceramics may be the key to further reducing exposure, but this
      presents challenges, as it involves a cultural tradition deeply rooted in Mexico.
      In addition, the creation of a rigorous, standardized, and on-going surveillance
      program of BLL is necessary for identifying vulnerable populations.

PMID- 30274370
TI  - SWIPT-Aware Fog Information Processing: Local Computing vs. Fog Offloading.
AB  - This paper studies a simultaneous wireless information and power transfer (SWIPT)
      aware fog computing by using a simple model, where a sensor harvests energy and
      receives information from a hybrid access point (HAP) through power splitting
      (PS) receiver architecture. Two information processing modes, local computing and
      fog offloading modes are investigated. For such a system, two optimization
      problems are formulated to minimize the sensor's required power for the two modes
      under the information rate and energy harvesting constraints by jointly
      optimizing the time assignment and the transmit power, as well as the PS ratio.
      The closed-form and semi-closed-form solutions to the proposed optimization
      problems are derived based on convex optimization theory. Simulation results show
      that neither mode is always superior to the other one. It also shows that when
      the number of logic operations per bit associated with local computing is less
      than a certain value, the local computing mode is a better choice; otherwise, the
      fog offloading mode should be selected. In addition, the mode selection
      associated with the positions of the user for fixed HAP and fog server (FS) is
      also discussed.

PMID- 30274372
TI  - UPLC-MS/MS Method for the Determination of 14 Compounds in Rat Plasma and Its
      Application in a Pharmacokinetic Study of Orally Administered Xiaoyao Powder.
AB  - Xiaoyao Powder (XYP), a common Chinese medicine, comprises eight traditional
      Chinese herbs and has been widely used clinically to treat liver damage and
      mental disorders. An ultra-performance liquid chromatography-tandem mass
      spectrometry method was developed to investigate the pharmacokinetics of 14
      compounds (albiflorin, paeoniflorin, ferulic acid, senkyunolide I, quercetin,
      isoliquiritigenin, atractylenolide III, ligustilide, atractylenolide II,
      liquiritin, liquiritigenin, saikosaponin c, glycyrrhizic acid, and saikosaponin
      a) in XYP. Naringenin was used as the internal standard. The compounds were
      separated using an ACQUITY UPLCTM BEH C18 column (1.7 MUm, 50 * 2.1 mm) with a
      mobile phase consisting of acetonitrile and 0.1% formic acid in water at a flow
      rate of 0.3 mL/min. Detection was performed on a triple-quadrupole tandem mass
      spectrometer using multiple reaction monitoring and an electrospray ionization
      source in both positive and negative ionization modes. All calibration curves
      exhibited good linearity (r2 > 0.9974) over the measured ranges. The intra- and
      inter-day precisions were within 12%, and the accuracy ranged from 89.93% to
      106.64%. Extraction recovery and matrix effect results were satisfactory. The
      method was successfully applied in a pharmacokinetic study of the 14 compounds in
      rat plasma after the oral administration of XYP.

PMID- 30274371
TI  - OPNa Overexpression Is Associated with Matrix Calcification in Thyroid Cancer
      Cell Lines.
AB  - Osteopontin (OPN) spliced variants (OPN-SV: OPNa, OPNb, and OPNc) are aberrantly
      expressed in tumors and frequently associated with cancer progression. This holds
      true for papillary thyroid carcinoma (PTC), which is the most common type of
      thyroid cancer (TC). PTC often presents with desmoplasia and dystrophic
      calcification, including psammoma bodies (PB). This work aimed to investigate
      total OPN (tOPN) and OPN-SV expression and their association with the presence of
      PB in the PTC classical variants (cPTC), as well as the involvement of OPN-SV in
      matrix calcification of TC cell lines. We found that cPTC samples presenting PB
      showed higher OPN expression levels. In TC cell lines, OPNa overexpression
      promotes higher matrix calcification and collagen synthesis when compared to that
      of clones overexpressing OPNb or OPNc. In response to OPN knockdown,
      calcification was inhibited, paralleled with the downregulation of calcification
      markers. In conclusion, our data evidenced that OPN expression is associated with
      the presence of PB in cPTC samples. Among the OPN-SV, OPNa is the main
      contributor to matrix calcification in tested TC cells, providing clues to a
      better understanding on the biology and ethiopathogenesis of the calcification
      process in TC cells.

PMID- 30274373
TI  - On the Performance of Cognitive Satellite-Terrestrial Relay Networks with Channel
      Estimation Error and Hardware Impairments.
AB  - This paper investigates the joint impact of channel estimation errors (CEEs) and
      hardware impairments (HIs) on the performance of a cognitive satellite
      terrestrial relay network (CSTRN), where the terrestrial and satellite links are
      considered following Rayleigh fading and shadowed Rician (SR) fading
      distributions, respectively. Besides, the terrestrial relay is working in half
      duplex decode-and-forward (DF) mode. By employing a general and practical model
      to account for both the CEEs and HIs at each link, the end-to-end signal-to-noise
      plus-distortion-and-error ratio (SNDER) is first obtained for the CSTRN. Then,
      closed-form expressions for the outage probability (OP) and throughput of the
      CSTRN are obtained, which allows us to demonstrate the aggregate impact of CEEs
      and HIs. In order to gain insightful findings, we further elaborate on the
      asymptotic OP and throughput at the high signal-to-noise-ratio (SNR) condition
      and quantitatively determine the fundamental performance ceiling. Finally, Monte
      Carlo (MC) computer simulations are provided to verify the correctness of the
      analytical results. Besides, with representative numerical analysis's help,
      interesting findings are presented.

PMID- 30274376
TI  - Can Photoplethysmography Replace Arterial Blood Pressure in the Assessment of
      Blood Pressure?
AB  - Arterial Blood Pressure (ABP) and photoplethysmography (PPG) are both useful
      techniques to monitor cardiovascular status. Though ABP monitoring is more widely
      employed, this procedure of signal acquisition whether done invasively or non
      invasively may cause inconvenience and discomfort to the patients. PPG, however,
      is simple, noninvasive, and can be used for continuous measurement. This paper
      focuses on analyzing the similarities in time and frequency domains between ABP
      and PPG signals for normotensive, prehypertensive and hypertensive subjects and
      the feasibility of the classification of subjects considering the results of the
      analysis performed. From a database with 120 records of ABP and PPG, each 120 s
      in length, the records where separated into epochs taking into account 10
      heartbeats, and the following statistical measures were performed: Correlation
      (r), Coherence (COH), Partial Coherence (pCOH), Partial Directed Coherence (PDC),
      Directed Transfer Function (DTF), Full Frequency Directed Transfer Function
      (ffDTF) and Direct Directed Transfer Function (dDTF). The correlation coefficient
      was r > 0.9 on average for all groups, indicating a strong morphology similarity.
      For COH and pCOH, coherence (linear correlation in frequency domain) was found
      with significance (p < 0.01) in differentiating between normotensive and
      hypertensive subjects using PPG signals. For the dataset at hand, only two
      synchrony measures are able to convincingly distinguish hypertensive subjects
      from normotensive control subjects, i.e., ffDTF and dDTF. From PDC, DTF, ffDTF,
      and dDTF, a consistent, a strong significant causality from ABP->PPG was found.
      When all synchrony measures were combined, an 87.5 % accuracy was achieved to
      detect hypertension using a Neural Network classifier, suggesting that PPG holds
      most informative features that exist in ABP.

PMID- 30274374
TI  - Implication and Regulation of AMPK during Physiological and Pathological Myeloid
      Differentiation.
AB  - AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine kinase
      consisting of the arrangement of various alpha? beta, and gamma?isoforms that are
      expressed differently depending on the tissue or the cell lineage. AMPK is one of
      the major sensors of energy status in mammalian cells and as such plays essential
      roles in the regulation of cellular homeostasis, metabolism, cell growth,
      differentiation, apoptosis, and autophagy. AMPK is activated by two upstream
      kinases, the tumor suppressor liver kinase B1 (LKB1) and the calcium/calmodulin
      dependent protein kinase kinase 2 (CAMKK2) through phosphorylation of the kinase
      on Thr172, leading to its activation. In addition, AMPK inhibits the mTOR pathway
      through phosphorylation and activation of tuberous sclerosis protein 2 (TSC2) and
      causes direct activation of unc-51-like autophagy activating kinase 1 (ULK1) via
      phosphorylation of Ser555, thus promoting initiation of autophagy. Although it is
      well established that AMPK can control the differentiation of different cell
      lineages, including hematopoietic stem cells (HSCs), progenitors, and mature
      hematopoietic cells, the role of AMPK regarding myeloid cell differentiation is
      less documented. The differentiation of monocytes into macrophages triggered by
      colony stimulating factor 1 (CSF-1), a process during which both caspase
      activation (independently of apoptosis induction) and AMPK-dependent stimulation
      of autophagy are necessary, is one noticeable example of the involvement of AMPK
      in the physiological differentiation of myeloid cells. The present review focuses
      on the role of AMPK in the regulation of the physiological and pathological
      differentiation of myeloid cells. The mechanisms of autophagy induction by AMPK
      will also be addressed, as autophagy has been shown to be important for
      differentiation of hematopoietic cells. In addition, myeloid malignancies
      (myeloid leukemia or dysplasia) are characterized by profound defects in the
      establishment of proper differentiation programs. Reinduction of a normal
      differentiation process in myeloid malignancies has thus emerged as a valuable
      and promising therapeutic strategy. As AMPK seems to exert a key role in the
      differentiation of myeloid cells, notably through induction of autophagy, we will
      also discuss the potential to target this pathway as a pro-differentiating and
      anti-leukemic strategy in myeloid malignancies.

PMID- 30274377
TI  - Typical Gaseous Semi-Volatile Metals Adsorption by Meta-Kaolinite: A DFT Study.
AB  - Kaolinite can be used as in-furnace adsorbent to capture gaseous semi-volatile
      metals during combustion, incineration, or gasification processes for the
      purposes of toxic metals emission control, ash deposition/slagging/corrosion
      inhibition, ultrafine particulate matter emission control, and so on. In this
      work, the adsorptions of typical heavy metals (Pb and Cd) and typical alkali
      metals (Na and K) by meta-kaolinite were investigated by the DFT calculation. The
      adsorption energies followed the sequence of NaOH-Si surface > KOH-Si surface >
      PbO-Al surface ~ CdO-Al surface ~ NaOH-Al surface > KOH-Al surface > NaCl-Al
      surface ~ Na-Si surface > Na-Al surface > KCl-Al surface > Pb-Al surface > PbCl2
      Al surface > CdCl2-Al surface ~ K-Si surface ~ PbCl-Al surface > K-Al surface >
      CdCl-Al surface > NaCl-Si surface > KCl-Si surface > Cd-Al surface. Si surface
      was found available to the adsorptions of Na, K, and their compounds, although it
      was invalid to the adsorptions of Pb, Cd, and their compounds. The interactions
      between adsorbates and surfaces were revealed. Furthermore, the discussion of
      combining with the experimental data was applied to the subject validity of
      calculation results and the effect of chlorine on adsorption and the effect of
      reducing atmosphere on adsorption.

PMID- 30274375
TI  - Alcohol and the Developing Brain: Why Neurons Die and How Survivors Change.
AB  - The consequences of alcohol drinking during pregnancy are dramatic and usually
      referred to as fetal alcohol spectrum disorders (FASD). This condition is one of
      the main causes of intellectual disability in Western countries. The immature
      fetal brain exposed to ethanol undergoes massive neuron death. However, the same
      mechanisms leading to cell death can also be responsible for changes of
      developmental plasticity. As a consequence of such a maladaptive plasticity, the
      functional damage to central nervous system structures is amplified and leads to
      permanent sequelae. Here we review the literature dealing with experimental FASD,
      focusing on the alterations of the cerebral cortex. We propose that the
      reciprocal interaction between cell death and maladaptive plasticity represents
      the main pathogenetic mechanism of the alcohol-induced damage to the developing
      brain.

PMID- 30274378
TI  - Inhibition of Experimental Choroidal Neovascularization by a Novel Peptide
      Derived from Calreticulin Anti-Angiogenic Domain.
AB  - Choroidal neovascularization (CNV) is a key pathological feature of several
      leading causes of vision loss including neovascular age-related macular
      degeneration. Here, we show that a calreticulin anti-angiogenic domain (CAD)-like
      peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube
      formation, migration of endothelial cells, and vascular sprouting from rat aortic
      ring explants. In a rat model of laser-induced CNV, we demonstrate that
      intravitreal injection of CAD27 significantly attenuated the formation of CNV
      lesions as measured via fundus fluorescein angiography and choroid flat-mounts
      (19.5% and 22.4% reductions at 10 MUg and 20 MUg of CAD27 injected,
      respectively). Similarly, the reduction of CNV lesions was observed in rats that
      had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5%
      reductions at 10 MUg/mL and 20 MUg/mL of CAD27 instilled, respectively). Retinal
      function was unaffected, as measured using electroretinography in both groups
      receiving interareal injection or topical applications of CAD27 for at least
      fourteen days. These findings show that CAD27 can be used as a potential
      therapeutic alternative for targeting CNV in diseases such as neovascular age
      related macular degeneration.

PMID- 30274379
TI  - Effect of Hybrid Carbon Fillers on the Electrical and Morphological Properties of
      Polystyrene Nanocomposites in Microinjection Molding.
AB  - The effect of hybrid carbon fillers of multi-walled carbon nanotubes (CNT) and
      carbon black (CB) on the electrical and morphological properties of polystyrene
      (PS) nanocomposites were systematically investigated in microinjection molding
      (MUIM). The polymer nanocomposites with three different filler concentrations
      (i.e., 3, 5 and 10 wt %) at various weight ratios of CNT/CB (100/0, 30/70, 50/50,
      70/30, 0/100) were prepared by melt blending, then followed by MUIM under a
      defined set of processing conditions. A rectangular mold insert which has three
      consecutive zones with decreasing thickness along the flow direction was adopted
      to study abrupt changes in mold geometry on the properties of resultant
      microparts. The distribution of carbon fillers within microparts was observed by
      scanning electron microscopy, which was correlated with electrical conductivity
      measurements. Results indicated that there is a flow-induced orientation of
      incorporated carbon fillers and this orientation increased with increasing
      shearing effect along the flow direction. High structure CB is found to be more
      effective than CNT in terms of enhancing the electrical conductivity, which was
      attributed to the good dispersion of CB in PS and their ability to form
      conductive networks via self-assembly. Morphology observations indicated that
      there is a shear-induced depletion of CB particles in the shear layer, which is
      due to the marked difference of shear rates between the shear and core layers of
      the molded microparts. Moreover, an annealing treatment is beneficial to enhance
      the electrical conductivity of CNT-containing microparts.

PMID- 30274380
TI  - Design, Synthesis, and Cytotoxic Analysis of Novel Hederagenin-Pyrazine
      Derivatives Based on Partial Least Squares Discriminant Analysis.
AB  - Hederagenin (He) is a novel triterpene template for the development of new
      antitumor compounds. In this study, 26 new He-pyrazine derivatives were
      synthetized in an attempt to develop potent antitumor agents; they were screened
      for in vitro cytotoxicity against tumor and non-tumor cell lines. The majority of
      these derivatives showed much stronger cytotoxic activity than He. Remarkably,
      the most potent was compound 9 (half maximal inhibitory concentration (IC50) was
      3.45 +/- 0.59 MUM), which exhibited similar antitumor activities against A549
      (human non-small-cell lung cancer) as the positive drug cisplatin (DDP; IC50 was
      3.85 +/- 0.63 MUM), while it showed lower cytotoxicity on H9c2 (murine heart
      myoblast; IC50 was 16.69 +/- 0.12 MUM) cell lines. Compound 9 could induce the
      early apoptosis and evoke cell-cycle arrest at the synthesis (S) phase of A549
      cells. Impressively, we innovatively introduced the method of cluster analysis
      modeled as partial least squares discriminant analysis (PLS-DA) into the
      structure-activity relationship (SAR) evaluation, and SAR confirmed that pyrazine
      had a profound effect on the antitumor activity of He. The present studies
      highlight the importance of pyrazine derivatives of He in the discovery and
      development of novel antitumor agents.

PMID- 30274381
TI  - Prostaglandin E1-Mediated Collateral Recruitment Is Delayed in a Neonatal Rat
      Stroke Model.
AB  - While arterial reflow after a stroke represents an important challenge for better
      outcomes, it is also very important that sudden recanalization does not produce
      local oxidative and nitrogen species, deleterious for the brain and more
      particularly the immature brain. Our objective was to determine whether a supply
      in prostaglandin (Pg) E1 (Alprostadil), via its action on arterial pressure,
      might progressively improve cerebral reperfusion in a neonatal stroke model.
      Arterial blood flow was measured using ultrasonography. Rate-limiting and Pg
      terminal synthesizing enzymes were evaluated using reverse-transcriptase
      polymerase chain reaction. Our data suggests that a supply in PgE1 might delay
      and improve the ipsilateral reperfusion by decreasing thromboxane A synthase-1
      gene, the density of reactive astrocytes and lesion volume.

PMID- 30274382
TI  - Robust Beamforming Design for Secure V2X Downlink System with Wireless
      Information and Power Transfer under a Nonlinear Energy Harvesting Model.
AB  - Vehicle to everything (V2X) has been deemed a promising technology due to its
      potential to achieve traffic safety and efficiency. This paper considers a V2X
      downlink system with a simultaneous wireless information and power transfer
      (SWIPT) system where the base station not only conveys data and energy to two
      types of wireless vehicular receivers, such as one hybrid power-splitting
      vehicular receiver, and multiple energy vehicular receivers, but also prevents
      information from being intercepted by the potential eavesdroppers (idle energy
      vehicular receivers). Both the base station and the energy vehicular receivers
      are equipped with multiple antennas, whereas the information vehicular receiver
      is equipped with a single antenna. In particular, the imperfect channel state
      information (CSI) and the practical nonlinear energy harvesting (EH) model are
      taken into account. The non-convex optimization problem is formulated to maximize
      the minimum harvested energy power among the energy vehicular receivers
      satisfying the lowest harvested energy power threshold at the information
      vehicular receiver and secure vehicular communication requirements. In light of
      the intractability of the optimization problem, the semidefinite relaxation (SDR)
      technique and variable substitutions are applied, and the optimal solution is
      proven to be tight. A number of results demonstrate that the proposed robust
      secure beamforming scheme has better performance than other schemes.

PMID- 30274383
TI  - Adaptive Ship Detection for Single-Look Complex SAR Images Based on SVWIE
      Noncircularity Decomposition.
AB  - In this paper, we present an adaptive ship detection method for single-look
      complex synthetic aperture radar (SAR) images. First, noncircularity is analyzed
      and adopted in ship detection task; besides, similarity variance weighted
      information entropy (SVWIE) is proposed for clutter reduction and target
      enhancement. According to the analysis of scattering of SVWIE and noncircularity,
      SVWIE-noncircularity (SN) decomposition is developed. Based on the decomposition,
      two components, the high-noncircularity SVWIE amplitude (h) and the low
      noncircularity SVWIE amplitude (l), are obtained. We demonstrate that ships and
      clutter in SAR images are different for h detector and h detector can be
      effectively used for ship detection. Finally, to extract ships from the
      background, the generalized Gamma distribution (G Gamma D) is used to fit h
      statistics of clutter and the constant false alarm rate (CFAR) is utilized to
      choose an adaptive threshold. The performance of the proposed method is
      demonstrated on HH polarization of Alos-2 images. Experimental results show that
      the proposed method can accurately detect ships in complex background, i.e.,
      ships are close to small islands or with strong noise.

PMID- 30274385
TI  - Sorbitol as a Chain Extender of Polyurethane Prepolymers to Prepare Self-Healable
      and Robust Polyhydroxyurethane Elastomers.
AB  - A self-healable polyhydroxyurethane (S-PU) was synthesized from sorbitol, a
      biomass of polyhydric alcohol, by a simple process that is suitable for practical
      applications. In the synthesis, only two primary hydroxyl groups of sorbitol were
      considered for the chain extension of the polyurethane (PU) prepolymers to
      introduce free hydroxyl groups in PU. As a control, conventional PU was
      synthesized by hexane diol mediated chain extension. Relative to the control, S
      PU showed excellent intrinsic self-healing property via exchange reaction, which
      was facilitated by the nucleophilic addition of the secondary hydroxyl groups
      without any catalytic assistance and improved tensile strength due to the
      enhanced hydrogen bonding. We also investigated the effect of the exchange
      reaction on the topological, mechanical, and rheological properties of S-PU. The
      suggested synthetic framework for S-PU is a promising alternative to the
      conventional poly hydroxyurethane, in which cyclic carbonates are frequently
      reacted with amines. As such, it is a facile and environmentally friendly
      material for use in coatings, adhesives, and elastomers.

PMID- 30274384
TI  - Effects of Restoration Time on Microbial Diversity in Rhizosphere and Non
      Rhizosphere Soil of Bothriochloa ischaemum.
AB  - There is well-documented evidence that shows phytoremediation and restoration
      methods affect physical and chemical properties, enzyme activities, and microbial
      communities of soil. In this study, we investigated the response of soil
      microbial communities to restoration time. We found that arsenic content
      decreased gradually as restoration progressed. Total carbon (C) in shoots and
      total nitrogen (N) in roots of B. ischaemum both exhibited increasing trends with
      an increase in restoration time. The transfer factor of chromium was negatively
      correlated to C in shoots and positively correlated to sulfur in roots.
      Additionally, the transfer factor of lead had a remarkably positive correlation
      to the C/N ratio of roots. For soil enzymes, total N in soil was positively
      correlated to catalase and urease but negatively correlated to sucrose. Moreover,
      bulk soil bacterial composition was positively correlated to catalase, sucrase
      and phosphatase while fungal diversity was positively correlated to sucrose. This
      study found that restoration time plays the most significant role in bacterial
      and fungal composition and bacterial diversity, but it has no effect on fungal
      diversity in rhizosphere and non-rhizosphere soil. In addition, the driving
      factors of microbial composition and diversity varied in rhizosphere and non
      rhizosphere soil among the different restoration time treatments.

PMID- 30274386
TI  - sEMG-Based Drawing Trace Reconstruction: A Novel Hybrid Algorithm Fusing Gene
      Expression Programming into Kalman Filter.
AB  - How to reconstruct drawing and handwriting traces from surface electromyography
      (sEMG) signals accurately has attracted a number of researchers recently. An
      effective algorithm is crucial to reliable reconstruction. Previously, nonlinear
      regression methods have been utilized successfully to some extent. In the quest
      to improve the accuracy of transient myoelectric signal decoding, a novel hybrid
      algorithm KF-GEP fusing Gene Expression Programming (GEP) into Kalman Filter (KF)
      framework is proposed for sEMG-based drawing trace reconstruction. In this work,
      the KF-GEP was applied to reconstruct fourteen drawn shapes and ten numeric
      characters from sEMG signals across five participants. Then the reconstruction
      performance of KF-GEP, KF and GEP were compared. The experimental results show
      that the KF-GEP algorithm performs best because it combines the advantages of KF
      and GEP. The findings add to the literature on the muscle-computer interface and
      can be introduced to many practical fields.

PMID- 30274387
TI  - Optical Micro/Nanofiber-Based Localized Surface Plasmon Resonance Biosensors:
      Fiber Diameter Dependence.
AB  - Integration of functional nanomaterials with optical micro/nanofibers (OMNFs) can
      bring about novel optical properties and provide a versatile platform for various
      sensing applications. OMNFs as the key element, however, have seldom been
      investigated. Here, we focus on the optimization of fiber diameter by taking
      micro/nanofiber-based localized surface plasmon resonance sensors as a model. We
      systematically study the dependence of fiber diameter on the sensing performance
      of such sensors. Both theoretical and experimental results show that, by reducing
      fiber diameter, the refractive index sensitivity can be significantly increased.
      Then, we demonstrate the biosensing capability of the optimized sensor for
      streptavidin detection and achieve a detection limit of 1 pg/mL. Furthermore, the
      proposed theoretical model is applicable to other nanomaterials and OMNF-based
      sensing schemes for performance optimization.

PMID- 30274388
TI  - Taurine and Methylprednisolone Administration at Close Proximity to the Onset of
      Muscle Degeneration Is Ineffective at Attenuating Force Loss in the Hind-Limb of
      28 Days Mdx Mice.
AB  - An increasing number of studies have shown supplementation with the amino acid
      taurine to have promise in ameliorating dystrophic symptoms in the mdx mouse
      model of Duchenne Muscular Dystrophy (DMD). Here we build on this limited body of
      work by investigating the efficacy of supplementing mdx mice with taurine
      postnatally at a time suggestive of when dystrophic symptoms would begin to
      manifest in humans, and when treatments would likely begin. Mdx mice were given
      either taurine (mdx tau), the steroid alpha methylprednisolone (PDN), or tau +
      PDN (mdx tau + PDN). Taurine (2.5% wt/vol) enriched drinking water was given from
      14 days and PDN (1 mg/kg daily) from 18 days. Wild-type (WT, C57BL10/ScSn) mice
      were used as a control to mdx mice to represent healthy tissue. In the mdx mouse,
      peak damage occurs at 28 days, and in situ assessment of contractile
      characteristics showed that taurine, PDN, and the combined taurine + PDN
      treatment was ineffective at attenuating the force loss experienced by mdx mice.
      Given the benefits of taurine as well as methylprednisolone reported previously,
      when supplemented at close proximity to the onset of severity muscle degeneration
      these benefits are no longer apparent.

PMID- 30274389
TI  - Structural and Magnetic Properties of Ni0.8Fe0.2/Ti Nanoscale Multilayers.
AB  - The influence of the thickness of the Ni0.8Fe0.2 (Permalloy, Py) layers on the
      structural and magnetic properties of magnetron sputtered Py/Ti multilayers was
      studied. The thickness of the Py layers was varied in the interval of 8 to 30 A.
      X-ray reflectivity scans evidence the existence of a well-defined layered
      structure in all the samples considered, but also the presence of a complex
      intermixed interface. The shape of both the temperature dependence of
      magnetization and the hysteresis loops of the multilayered structures depends
      strongly on Py thickness. Magnetic and reflectivity measurements were
      comparatively analyzed in order to better understand the structure of the
      samples, and specifically, their interfaces. In particular, the presence of small
      superparamagnetic Py at the interfaces of the samples, especially evident in the
      samples with the thinnest Py layers, seems confirmed by the magnetic
      measurements, agreeing well with the reflectivity results.

PMID- 30274390
TI  - Lewis Acidity and Basicity of Mixed Chlorometallate Ionic Liquids: Investigations
      from Surface Analysis and Fukui Function.
AB  - Mixed chlorometallate ionic liquids (ILs) have been regarded as potential
      solvents, catalysts, and reagents for many organic processes. The acidity and
      basicity of these ILs were correlated with theoretically estimated parameters
      such as electrostatic surface potential maxima and minima, average local surface
      ionization energy, and Fukui and dual descriptor functions. The introduction of
      metal chloride into the anions would influence the acidity/basicity of ILs by
      withdrawing the electron density from the cationic counterpart. For the [C4mim]
      based ILs with the mixed-metal anions, the acidity tends to attenuate while the
      basicity becomes stronger, as compared to the corresponding chloroaluminate ILs.
      However, the acidity of [(C2H5)3NH]-based ILs with the mixed-metal anions are
      greater than that of the net chloroaluminate ILs. The Fukui function values
      showed that most of the mixed chlorometallate ILs belong to bifunctional
      distribution. The mixed chlorometallate ILs both have electrophilic and
      nucleophilic sites, which would be beneficial for their applications.

PMID- 30274391
TI  - Educational Attainment Better Protects African American Women than African
      American Men Against Depressive Symptoms and Psychological Distress.
AB  - BACKGROUND: Recent research has shown smaller health effects of socioeconomic
      status (SES) indicators such as education attainment for African Americans as
      compared to whites. However, less is known about diminished returns based on
      gender within African Americans. AIM: To test whether among African American men
      are at a relative disadvantage compared to women in terms of having improved
      mental health as a result of their education attainment. This study thus explored
      gender differences in the association between education attainment and mental
      health, using a representative sample of American adults. METHODS: The National
      Survey of American Life (NSAL; 2003) recruited 3570 African American adults (2299
      females and 1271 males). The dependent variables were depressive symptoms and
      psychological distress. The independent variable was education attainment. Race
      was the focal moderator. Age, employment status, and marital status were
      covariates. Linear regressions were used for data analysis. RESULTS: In the
      pooled sample that included both male and female African American adults, high
      education attainment was associated with lower depressive symptoms and
      psychological distress, net of covariates. Significant interactions were found
      between gender and education attainment with effects on depressive symptoms and
      psychological distress, suggesting stronger protective effects of high education
      attainment against depressive symptoms and psychological distress for female as
      compared to male African Americans. CONCLUSION: A smaller gain in mental health
      with respect to educational attainment for male African American males as
      compared to African American females is in line with studies showing high risk of
      depression in African American men of high-socioeconomic status. High-SES African
      American men need screening for depression and psychological distress.

PMID- 30274392
TI  - Modification Effects of B2O3 on The Structure and Catalytic Activity of WO3-UiO
      66 Catalyst.
AB  - Tungsten oxide (WO3) and boron oxide (B2O3) were irreversibly encapsulated into
      the nanocages of the Zr-based metal organic framework UiO-66, affording a hybrid
      material B2O3-WO3/UiO-66 by a simple microwave-assisted deposition method. The
      novel B2O3-WO3/UiO-66 material was systematically characterized by X-ray
      diffraction, Fourier transform infrared spectroscopy, N2 adsorption, ultraviolet
      visible diffuse reflectance spectroscopy, scanning electron microscopy,
      transmission electron microscopy, X-ray phosphorescence, and Fourier transform
      infrared (FTIR)-CO adsorption methods. It was found that WO3 and B2O3 were highly
      dispersed in the nanocages of UiO-66, and the morphology and crystal structure of
      UiO-66 were well preserved. The B2O3 species are wrapped by WO3 species, thus
      increasing the polymeric degree of the WO3 species, which are mainly located in
      low-condensed oligomeric environments. Moreover, when compared with WO3/UiO-66,
      the B2O3-WO3/UiO-66 material has a little weaker acidity, which decreased by 10%
      upon the B2O3 introduction. The as-obtained novel material exhibits higher
      catalytic performance in the cyclopentene selective oxidation to glutaraldehyde
      than WO3/UiO-66. The high catalytic performance was attributed to a proper amount
      of B2O3 and WO3 with an appropriate acidity, their high dispersion, and the
      synergistic effects between them. In addition, these oxide species hardly leached
      in the reaction solution, endowing the catalyst with a good stability. The
      catalyst could be used for six reaction cycles without an obvious loss of
      catalytic activity.

PMID- 30274395
TI  - Point Score Systems and Cooperative Incentives: The 3-1-0 Curse.
AB  - The purpose of this study is to analyze the consequences that point score systems
      in association football may have on potential collusion between teams. The study
      applies game theory and empirical analysis to derive and test hypotheses. The
      main findings of the article include Nash equilibria indicating a higher
      collusion potential associated with the 3-1-0 point score system than with the 2
      1-0 system. Of particular interest is the finding that the competitive balance of
      the league affects collusion, and that (theoretically) high competitive balance
      in fact makes collusion more probable. Empirically, we are not able to prove that
      real-world participants do collude, but we provide circumstantial evidence that
      is consistent with collusion. The empirical analysis is based on a sample of 25
      European top leagues with 823 played matches in the 2017 and 2016/17 seasons.
      These data are used to estimate uncertainty of outcome and draw ratio. We apply a
      standard t-test to test our main hypothesis. The main conclusion of the paper may
      hence be summed up as advice to reinstall the 2-1-0 point score system in
      association football.

PMID- 30274393
TI  - Teacher Discrimination Reduces School Performance of African American Youth: Role
      of Gender.
AB  - : Background: Gender may alter African Americans' vulnerability to
      discrimination. The type of outcomes that follow exposure to discrimination may
      also be gender-specific. Although teacher discrimination is known to deteriorate
      school performance, it is yet unknown whether male and female African American
      youth differ in the effect of teacher discrimination on school performance.
      Objective: This cross-sectional study explored the moderating role of gender on
      the effect of teacher discrimination on school performance in a national sample
      of African American youth. Methods: The National Survey of American Life
      Adolescent Supplement (NSAL-A) enrolled a nationally representative sample (n =
      810) of 13-17-year-old African American youth. Demographic factors, socioeconomic
      status, teacher discrimination, and school performance (grade point average, GPA)
      were measured. Linear multivariable regression models were applied for data
      analysis. RESULTS: Males and females reported similar levels of perceived teacher
      discrimination. In the pooled sample, higher teacher discrimination was
      associated with lower school performance among African American youth (b = -0.35;
      95% confidence interval (CI) = -0.49 to -0.22). Gender interacted with perceived
      teacher discrimination (b = 12; 95% CI = 0.24-2.02), suggesting a significant
      difference between males and females in the magnitude of the association between
      perceived teacher discrimination and GPA. In stratified models, perceived teacher
      discrimination was associated with worse school performance of females (b = -12;
      95% CI = -0.03 to -2.78) but not males (b = 0.01; 95% CI = -0.07 to 0.08).
      CONCLUSION: In line with previous studies, gender was found to alter the
      vulnerability of African American youth to perceived discrimination. African
      American boys and girls may differ in their sensitivity to the effects of teacher
      discrimination on school performance.

PMID- 30274394
TI  - Human Mesenchymal Stem Cell Secretome from Bone Marrow or Adipose-Derived Tissue
      Sources for Treatment of Hypoxia-Induced Pulmonary Epithelial Injury.
AB  - : : Alveolar epithelial dysfunction induced by hypoxic stress plays a significant
      role in the pathological process of lung ischemia-reperfusion injury (IRI).
      Mesenchymal stem cell (MSC) therapies have demonstrated efficacy in exerting
      protective immunomodulatory effects, thereby reducing airway inflammation in
      several pulmonary diseases. AIM: This study assesses the protective effects of
      MSC secretome from different cell sources, human bone marrow (BMSC) and adipose
      tissue (ADSC), in attenuating hypoxia-induced cellular stress and inflammation in
      pulmonary epithelial cells. METHODS: Pulmonary epithelial cells, primary rat
      alveolar epithelial cells (AEC) and A549 cell line were pre-treated with BMSC, or
      ADSC conditioned medium (CM) and subjected to hypoxia for 24 h. RESULTS: Both MSC
      CM improved cell viability, reduced secretion of pro-inflammatory mediators and
      enhanced IL-10 anti-inflammatory cytokine production in hypoxic injured primary
      rat AECs. ADSC-CM reduced hypoxic cellular injury by mechanisms which include:
      inhibition of p38 MAPK phosphorylation and nuclear translocation of subunits in
      primary AECs. Both MSC-CM enhanced translocation of Bcl-2 to the nucleus,
      expression of cytoprotective glucose-regulated proteins (GRP) and restored matrix
      metalloproteinases (MMP) function, thereby promoting repair and cellular
      homeostasis, whereas inhibition of GRP chaperones was detrimental to cell
      survival. CONCLUSIONS: Elucidation of the protective mechanisms exerted by the
      MSC secretome is an essential step for maximizing the therapeutic effects, in
      addition to developing therapeutic targets-specific strategies for various
      pulmonary syndromes.

PMID- 30274396
TI  - An Improved Strapdown Inertial Navigation System Initial Alignment Algorithm for
      Unmanned Vehicles.
AB  - Along with the development of computer technology and informatization, the
      unmanned vehicle has become an important equipment in military, civil and some
      other fields. The navigation system is the basis and core of realizing the
      autonomous control and completing the task for unmanned vehicles, and the
      Strapdown Inertial Navigation System (SINS) is the preferred due to its autonomy
      and independence. The initial alignment technique is the premise and the
      foundation of the SINS, whose performance is susceptible to system nonlinearity
      and uncertainty. To improving system performance for SINS, an improved initial
      alignment algorithm is proposed in this manuscript. In the procedure of this
      presented initial alignment algorithm, the original signal of inertial sensors is
      denoised by utilizing the improved signal denoising method based on the Empirical
      Mode Decomposition (EMD) and the Extreme Learning Machine (ELM) firstly to
      suppress the high-frequency noise on coarse alignment. Afterwards, the accuracy
      and reliability of initial alignment is further enhanced by utilizing an improved
      Robust Huber Cubarure Kalman Filer (RHCKF) method to minimize the influence of
      system nonlinearity and uncertainty on the fine alignment. In addition, real
      tests are used to verify the availability and superiority of this proposed
      initial alignment algorithm.

PMID- 30274397
TI  - Altered Proteins in the Hippocampus of Patients with Mesial Temporal Lobe
      Epilepsy.
AB  - Mesial temporal lobe epilepsy (MTLE) is usually associated with drug-resistant
      seizures and cognitive deficits. Efforts have been made to improve the
      understanding of the pathophysiology of MTLE for new therapies. In this study, we
      used proteomics to determine the differential expression of proteins in the
      hippocampus of patients with MTLE compared to control samples. By using the two
      dimensional electrophoresis method (2-DE), the proteins were separated into spots
      and analyzed by LC-MS/MS. Spots that had different densitometric values for
      patients and controls were selected for the study. The following proteins were
      found to be up-regulated in patients: isoform 1 of serum albumin (ALB), proton
      ATPase catalytic subunit A (ATP6V1A), heat shock protein 70 (HSP70),
      dihydropyrimidinase-related protein 2 (DPYSL2), isoform 1 of myelin basic protein
      (MBP), and dihydrolipoamide S-acethyltransferase (DLAT). The protein isoform 3 of
      the spectrin alpha chain (SPTAN1) was down-regulated while glutathione S
      transferase P (GSTP1) and protein DJ-1 (PARK7) were found only in the hippocampus
      of patients with MTLE. Interactome analysis of the nine proteins of interest
      revealed interactions with 20 other proteins, most of them involved with
      metabolic processes (37%), presenting catalytic activity (37%) and working as
      hydrolyses (25%), among others. Our results provide evidence supporting a direct
      link between synaptic plasticity, metabolic disturbance, oxidative stress with
      mitochondrial damage, the disruption of the blood-brain barrier and changes in
      CNS structural proteins with cell death and epileptogenesis in MTLE. Besides
      this, the presence of markers of cell survival indicated a compensatory
      mechanism. The over-expression of GSTP1 in MTLE could be related to drug
      resistance.

PMID- 30274398
TI  - Traceability of "Tuscan PGI" Extra Virgin Olive Oils by 1H NMR Metabolic Profiles
      Collection and Analysis.
AB  - According to Coldiretti, Italy still continues to hold the European Quality
      record in extra virgin olive oils with origin designation and protected
      geographical indication (PDO and PGI). To date, 46 Italian brands are recognized
      by the European Union: 42 PDO and 4 PGI (Tuscan PGI, Calabria PGI; Tuscia PGI and
      PGI Sicily). Specific regulations, introduced for these quality marks, include
      the designation of both the geographical areas and the plant varieties
      contributing to the composition of the olive oil. However, the PDO and PGI
      assessment procedures are currently based essentially on farmer declarations.
      Tuscan PGI extra virgin olive oil is one of the best known Italian trademarks
      around the world. Tuscan PGI varietal platform is rather wide including 31
      specific olive cultivars which should account for at least 95% of the product. On
      the other hand, while the characteristics of other popular Italian extra virgin
      olive oils (EVOOs) cultivars from specific geographical areas have been
      extensively studied (such as those of Coratina based blends from Apulia), little
      is still known about Tuscan PGI EVOO constituents. In this work, we performed,
      for the first time, a large-scale analysis of Tuscan PGI monocultivar olive oils
      by 1H NMR spectroscopy and multivariate statistical analyses (MVA). After genetic
      characterization of 217 leaf samples from 24 selected geographical areas,
      distributed all over the Tuscany, a number of 202 micro-milled oil samples
      including 10 PGI cultivars, was studied. The results of the present work
      confirmed the need of monocultivar genetically certified EVOO samples for the
      construction of 1H-NMR-metabolic profiles databases suitable for cultivar and/or
      geographical origin assessment. Such specific PGI EVOOs databases could be
      profitably used to justify the high added value of the product and the
      sustainability of the related supply chain.

PMID- 30274399
TI  - Neuronal Activity-Dependent Activation of Astroglial Calcineurin in Mouse Primary
      Hippocampal Cultures.
AB  - Astrocytes respond to neuronal activity by generating calcium signals which are
      implicated in the regulation of astroglial housekeeping functions and/or in
      modulation of synaptic transmission. We hypothesized that activity-induced
      calcium signals in astrocytes may activate calcineurin (CaN), a
      calcium/calmodulin-regulated protein phosphatase, implicated in neuropathology,
      but whose role in astroglial physiology remains unclear. We used a lentiviral
      vector expressing NFAT-EYFP (NY) fluorescent calcineurin sensor and a chemical
      protocol of LTP induction (cLTP) to show that, in mixed neuron-astrocytic
      hippocampal cultures, cLTP induced robust NY translocation into astrocyte nuclei
      and, hence, CaN activation. NY translocation was abolished by the CaN inhibitor
      FK506, and was not observed in pure astroglial cultures. Using Fura-2 single cell
      calcium imaging, we found sustained Ca2+ elevations in juxtaneuronal, but not
      distal, astrocytes. Pharmacological analysis revealed that both the Ca2+ signals
      and the nuclear NY translocation in astrocytes required NMDA and mGluR5 receptors
      and depended on extracellular Ca2+ entry via a store-operated mechanism. Our
      results provide a proof of principle that calcineurin in astrocytes may be
      activated in response to neuronal activity, thereby delineating a framework for
      investigating the role of astroglial CaN in the physiology of central nervous
      system.

PMID- 30274400
TI  - The Re-Emergence and Emergence of Vector-Borne Rickettsioses in Taiwan.
AB  - Rickettsial diseases, particularly vector-borne rickettsioses (VBR), have a long
      history in Taiwan, with studies on scrub typhus and murine typhus dating back
      over a century. The climatic and geographic diversity of Taiwan's main island and
      its offshore islands provide many ecological niches for the diversification and
      maintenance of rickettsiae alike. In recent decades, scrub typhus has re-emerged
      as the most prevalent type of rickettsiosis in Taiwan, particularly in eastern
      Taiwan and its offshore islands. While murine typhus has also re-emerged on
      Taiwan's western coast, it remains neglected. Perhaps more alarming than the re
      emergence of these rickettsioses is the emergence of newly described VBR. The
      first case of human infection with Rickettsia felis was confirmed in 2005, and
      undetermined spotted fever group rickettsioses have recently been detected.
      Taiwan is at a unique advantage in terms of detecting and characterizing VBR, as
      it has universal health coverage and a national communicable disease surveillance
      system; however, these systems have not been fully utilized for this purpose.
      Here, we review the existing knowledge on the eco-epidemiology of VBR in Taiwan
      and recommend future courses of action.

PMID- 30274403
TI  - Mosquitoes and the Lymphatic Filarial Parasites: Research Trends and Budding
      Roadmaps to Future Disease Eradication.
AB  - The mosquito-borne lymphatic filariasis (LF) is a parasitic, neglected tropical
      disease that imposes an unbearable human scourge. Despite the unprecedented
      efforts in mass drug administration (MDA) and morbidity management, achieving the
      global LF elimination slated for the year 2020 has been thwarted by limited MDA
      coverage and ineffectiveness in the chemotherapeutic intervention. Moreover,
      successful and sustainable elimination of mosquito-vectored diseases is often
      encumbered by reintroduction and resurgence emanating from human residual or new
      infections being widely disseminated by the vectors even when chemotherapy proves
      effective, but especially in the absence of effective vaccines. This created
      impetus for strengthening the current defective mosquito control approach, and
      profound research in vector-pathogen systems and vector biology has been pushing
      the boundaries of ideas towards developing refined vector-harnessed control
      strategies. Eventual implementation of these emerging concepts will offer a
      synergistic approach that will not only accelerate LF elimination, but also
      augurs well for its future eradication. This brief review focuses on advances in
      mosquito-filaria research and considers the emerging prospects for future
      eradication of LF.

PMID- 30274401
TI  - Suspected and Confirmed Vector-Borne Rickettsioses of North America Associated
      with Human Diseases.
AB  - The identification of pathogenic rickettsial agents has expanded over the last
      two decades. In North America, the majority of human cases are caused by tick
      borne rickettsioses but rickettsiae transmitted by lice, fleas, mites and other
      arthropods are also responsible for clinical disease. Symptoms are generally
      nonspecific or mimic other infectious diseases; therefore, diagnosis and
      treatment may be delayed. While infection with most rickettsioses is relatively
      mild, delayed diagnosis and treatment may lead to increased morbidity and
      mortality. This review will discuss the ecology, epidemiology and public health
      importance of suspected and confirmed vector-transmitted Rickettsia species of
      North America associated with human diseases.

PMID- 30274402
TI  - Tick-, Flea-, and Louse-Borne Diseases of Public Health and Veterinary
      Significance in Nigeria.
AB  - Mosquito-borne diseases are common high-impact diseases in tropical and
      subtropical areas. However, other non-mosquito vector-borne pathogens (VBPs) may
      share their geographic distribution, seasonality, and clinical manifestations,
      thereby contributing their share to the morbidity and mortality caused by febrile
      illnesses in these regions. The purpose of this work was to collect and review
      existing information and identify knowledge gaps about tick, flea-, and louse
      borne diseases of veterinary and public health significance in Nigeria. Full
      length articles about VBPs were reviewed and relevant information about the
      vectors, their hosts, geographic distribution, seasonality, and association(s)
      with human or veterinary diseases was extracted. Specific laboratory tools used
      for detection and identification of VBPs in Nigeria were also identified. A total
      of 62 original publications were examined. Substantial information about the
      prevalence and impacts of ticks and fleas on pet and service dogs (18 articles),
      and livestock animals (23 articles) were available; however, information about
      their association with and potential for causing human illnesses was largely
      absent despite the zoonotic nature of many of these peri-domestic veterinary
      diseases. Recent publications that employed molecular methods of detection
      demonstrated the occurrence of several classic (Ehrlichia canis, Rickettsia
      africae, Bartonella sp.) and emerging human pathogens (R. aeschlimannii,
      Neoehrlichia mikurensis) in ticks and fleas. However, information about other
      pathogens often found in association with ticks (R. conorii) and fleas (R. typhi,
      R. felis) across the African continent was lacking. Records of louse-borne
      epidemic typhus in Nigeria date to 1947; however, its current status is not
      known. This review provides an essential baseline summary of the current
      knowledge in Nigeria of non-mosquito VBPs, and should stimulate improvements in
      the surveillance of the veterinary and human diseases they cause in Nigeria. Due
      to increasing recognition of these diseases in other African countries,
      veterinary and public health professionals in Nigeria should expand the list of
      possible diseases considered in patients presenting with fever of unknown
      etiology.

PMID- 30274404
TI  - Application of Artificial Neural Networks for Dengue Fever Outbreak Predictions
      in the Northwest Coast of Yucatan, Mexico and San Juan, Puerto Rico.
AB  - Modelling dengue fever in endemic areas is important to mitigate and improve
      vector-borne disease control to reduce outbreaks. This study applied artificial
      neural networks (ANNs) to predict dengue fever outbreak occurrences in San Juan,
      Puerto Rico (USA), and in several coastal municipalities of the state of Yucatan,
      Mexico, based on specific thresholds. The models were trained with 19 years of
      dengue fever data for Puerto Rico and six years for Mexico. Environmental and
      demographic data included in the predictive models were sea surface temperature
      (SST), precipitation, air temperature (i.e., minimum, maximum, and average),
      humidity, previous dengue cases, and population size. Two models were applied for
      each study area. One predicted dengue incidence rates based on population at risk
      (i.e., numbers of people younger than 24 years), and the other on the size of the
      vulnerable population (i.e., number of people younger than five years and older
      than 65 years). The predictive power was above 70% for all four model runs. The
      ANNs were able to successfully model dengue fever outbreak occurrences in both
      study areas. The variables with the most influence on predicting dengue fever
      outbreak occurrences for San Juan, Puerto Rico, included population size,
      previous dengue cases, maximum air temperature, and date. In Yucatan, Mexico, the
      most important variables were population size, previous dengue cases, minimum air
      temperature, and date. These models have predictive skills and should help dengue
      fever mitigation and management to aid specific population segments in the
      Caribbean region and around the Gulf of Mexico.

PMID- 30274405
TI  - Clinical Features and Laboratory Findings of Travelers Returning to South
      Australia with Dengue Virus Infection.
AB  - Reported cases of dengue are rising in South Australia (SA) in travellers
      returning from dengue-endemic regions. We have undertaken a retrospective
      analysis to identify the clinical and laboratory characteristics of patients
      returning to SA with suspected dengue virus (DENV) infection. From 488 requests,
      49 (10%) were defined by serology as acute dengue, with the majority of patients
      (75%) testing as non-structural protein 1 (NS1) and/or IgM positive. Dengue was
      most commonly acquired in Indonesia (42.9%) with clinical features of fever
      (95%), headache (41%) and myalgia/arthralgia (56%). The presence of rash (36%)
      and laboratory findings of neutropenia, leukopenia, thrombocytopenia, but not
      elevated C-reactive protein, were distinct from findings in DENV-seronegative
      patients. Available dengue seropositive samples were analysed by RT-PCR, with
      14/32 (43.8%) positive by a serotype non-specific DENV assay, but 28/32 positive
      (87.5%) when also assessed by serotype-specific RT-PCR. Serotype analysis
      revealed the predominance of DENV-1 and DENV-2 and the presence of DENV-3, but
      not DENV-4 or Zika virus (ZIKV). Thus, dengue in returned travellers in SA
      presents in a manner consistent with World Health Organization (WHO) definitions,
      with symptoms, travel history and laboratory results useful in prioritising the
      likelihood of dengue. This definition will assist the future management in DENV
      non-endemic regions, such as SA.

PMID- 30274408
TI  - The Rise of Imported Dengue Infections in Victoria, Australia, 2010-2016.
AB  - Dengue notifications have increased dramatically over the past seven years in
      Victoria, Australia-a trend which has been seen nationally and reflects increased
      cases internationally. We reviewed the epidemiology of dengue among Victorian
      travellers, changes in diagnostic methods and describe the burden placed on local
      health systems resulting from this disease of public health importance. Cases of
      dengue notified to the Department of Health and Human Services in Victoria,
      Australia, between 1 January 2010 and 31 December 2016 were included in this
      review. Demographic, clinical, diagnostic methods, and risk factor data were
      examined using descriptive epidemiological analyses. Cases of dengue increased on
      average by 22% per year, with a total of 2187 cases (5.5 cases/100,000
      population) notified over the 7-year reporting period. The most frequently
      reported country of acquisition was Indonesia (45%) followed by Thailand (14%).
      The use of multiple diagnostic methods, including the non-structural protein 1
      antigen (NS1Ag) detection test, increased over time. The median time between
      onset of illness and diagnosis diminished from 9 days (IQR: 2-15) in 2010 to 4
      days (IQR: 2-7) in 2016. Proportionally more cases were discharged directly from
      emergency departments in recent years (10% in 2010 to 28% in 2016, p < 0.001).The
      increasing incidence of dengue in Australia is reflective of its growing
      prominence as a travel medicine problem in western countries. For travellers with
      non-severe dengue, the improved timeliness of dengue diagnostics allows for
      consideration of best practice ambulatory management approaches as used in
      endemic areas.

PMID- 30274409
TI  - Scrub Typhus: No Longer Restricted to the Tsutsugamushi Triangle.
AB  - Scrub typhus is the most important rickettsial disease in the world. Its previous
      endemic region was considered to be in Asia, Australia and islands in the Indian
      and Pacific Oceans; this area was referred to as the Tsutsugamushi Triangle.
      Accumulation of serological, molecular, genetic, and culture data have shown that
      not only is scrub typhus not limited to the Tsutsugamushi Triangle, but can be
      caused by orientiae other than Orientia tsutsugamushi. This review describes
      evidence currently available that will be instrumental to researchers, healthcare
      providers and medical leaders in developing new research projects, performing
      diagnosis, and preventing scrub typhus in locations not previously thought to be
      endemic.

PMID- 30274411
TI  - Global Burden and Challenges of Melioidosis.
AB  - Melioidosis, an infectious disease caused by the environmental bacterium
      Burkholderia pseudomallei, has remained in the shadows for far too long[...].

PMID- 30274407
TI  - A Review of Scrub Typhus (Orientia tsutsugamushi and Related Organisms): Then,
      Now, and Tomorrow.
AB  - Scrub typhus and the rickettsial diseases represent some of the oldest recognized
      vector-transmitted diseases, fraught with a rich historical aspect, particularly
      as applied to military/wartime situations. The vectors of Orientia tsutsugamushi
      were once thought to be confined to an area designated as the Tsutsugamushi
      Triangle. However, recent reports of scrub typhus caused by Orientia species
      other than O. tsutsugamushi well beyond the limits of the Tsutsugamushi Triangle
      have triggered concerns about the worldwide presence of scrub typhus. It is not
      known whether the vectors of O. tsutsugamushi will be the same for the new
      Orientia species, and this should be a consideration during outbreak/surveillance
      investigations. Additionally, concerns surrounding the antibiotic resistance of
      O. tsutsugamushi have led to considerations for the amendment of treatment
      protocols, and the need for enhanced public health awareness in both the civilian
      and medical professional communities. In this review, we discuss the history,
      outbreaks, antibiotic resistance, and burgeoning genomic advances associated with
      one of the world's oldest recognized vector-borne pathogens, O. tsutsugamushi.

PMID- 30274410
TI  - Rickettsial Infections and Q Fever Amongst Febrile Patients in Bhutan.
AB  - There is limited evidence of rickettsial diseases in Bhutan. We explored the
      contribution of rickettsioses as a cause of undifferentiated febrile illness in
      patients presenting to 14 Bhutanese hospitals from October 2014 to June 2015.
      Obvious causes of fever were excluded clinically. Clinico-demographic information
      and acute blood samples were collected. Samples were tested by immunofluorescence
      assay (IFA) and qPCR against scrub typhus group (STG), spotted fever group (SFG)
      and typhus group (TG) rickettsiae, and Q fever (QF). Of the 1044 patients, 539
      (51.6%) were female and the mean age was 31.5 years. At least 159 (15.2%) of the
      patients had evidence of a concurrent rickettsial infection. Of these, 70 (6.7%),
      46 (4.4%), 4 (0.4%), and 29 (2.8%) were diagnosed as acute infections with STG,
      SFG, TG, and QF respectively. Ten (1.0%) patients were seropositive for both SFG
      and TG. Seven of the 70 STG patients were positive by qPCR. Eschar (p < 0.001),
      myalgia (p = 0.003), and lymphadenopathy (p = 0.049) were significantly
      associated with STG, but no specific symptoms were associated with the other
      infections. Disease incidences were not different between age groups, genders,
      occupations, and districts, except for students with significantly lower odds of
      infection with STG (OR = 0.43; 95% CI = 0.20, 0.93; p = 0.031). Rickettsioses
      were responsible for at least 15% of undifferentiated febrile illnesses in
      Bhutan, scrub typhus being the commonest. Health authorities should ensure that
      health services are equipped to manage these infections.

PMID- 30274412
TI  - Development and Clinical Validation of a Multiplex Real-Time Quantitative PCR
      Assay for Human Infection by Anaplasma phagocytophilum and Ehrlichia chaffeensis.
AB  - BACKGROUND: Human granulocytic anaplasmosis (HGA), caused by Anaplasma
      phagocytophilum, and human monocytic ehrlichiosis (HME), caused by Ehrlichia
      chaffeensis, often present as undifferentiated fever but are not treated by
      typical empiric regimens for acute febrile illness. Their role as agents of
      vector-borne febrile disease in tropical regions is more poorly studied than for
      other rickettsial infections. Limitations in diagnosis have impaired
      epidemiologic and clinical research and needless morbidity and mortality occur
      due to untreated illness. METHODS: We designed and clinically validated a
      multiplex real-time quantitative PCR assay for Anaplasma phagocytophilum and
      Ehrlichia chaffeensis using samples confirmed by multiple gold-standard methods.
      RESULTS: Clinical sensitivity and specificity for A. phagocytophilum were 100%
      (39/39) and 100% (143/143), respectively, and for E. chaffeensis 95% (20/21) and
      99% (159/161), respectively. CONCLUSIONS: These assays could support early
      diagnosis and treatment as well as the high-throughput testing required for large
      epidemiologic studies.

PMID- 30274413
TI  - Cross-Cultural, Aboriginal Language, Discovery Education for Health Literacy and
      Informed Consent in a Remote Aboriginal Community in the Northern Territory,
      Australia.
AB  - BACKGROUND: Education for health literacy of Australian Aboriginal people living
      remotely is challenging as their languages and worldviews are quite different
      from English language and Western worldviews. Becoming health literate depends on
      receiving comprehensible information in a culturally acceptable manner. METHODS:
      The study objective was to facilitate oral health literacy through community
      education about scabies and strongyloidiasis, including their transmission and
      control, preceding an ivermectin mass drug administration (MDA) for these
      diseases. A discovery education approach where health concepts are connected to
      cultural knowledge in the local language was used. Aboriginal and non-Aboriginal
      educators worked collaboratively to produce an in-depth flip-chart of the
      relevant stories in the local language and to share them with clan elders and 27%
      of the population. RESULTS: The community health education was well received.
      Feedback indicated that the stories were being discussed in the community and
      that the mode of transmission of strongyloidiasis was understood. Two-thirds of
      the population participated in the MDA. This study documents the principles and
      practice of a method of making important Western health knowledge comprehensible
      to Aboriginal people. This method would be applicable wherever language and
      culture of the people differ from language and culture of health professionals.

PMID- 30274414
TI  - Community Awareness on Rabies Prevention and Control in Bicol, Philippines: Pre-
      and Post-Project Implementation.
AB  - Rabies is endemic in the Philippines. To support the rabies campaign in the Bicol
      region at the southeastern part of Luzon, the BAI-OIE Stop Transboundary Animal
      Diseases and Zoonoses (STANDZ) Rabies project was implemented in the pilot
      provinces of Camarines Norte, Camarines Sur, Albay, and Masbate. A community
      awareness survey was conducted with the residents of these provinces to determine
      their knowledge, attitude, and practices (KAP) on rabies during the start and end
      of the project. Qualitative, descriptive research was done with a structured KAP
      questionnaire. Pet owners in the pilot provinces were chosen as respondents.
      Results showed that respondents know that they can acquire rabies in animals
      through the bite of a rabid dog (pre-project implementation (PRI): 19.6%, post
      project implementation (POI): 38.0%). Vaccination was the top rabies preventive
      measure (PRI: 61.8%, POI: 92.8%). Biting incidents were noted in some
      respondents, and observing the dog and killing it immediately were some of the
      actions taken by bite victims. If a supposed rabid dog was seen, respondents
      would either: immediately kill the dog (PRI: 20.3%, POI: 13.7%), report it to
      authorities (PRI: 26.3%, POI: 63.1%), and capture and observe the dog concerned
      (PRI: 13.5%, POI: 6.0%). Pet owners increased their KAP about rabies prevention
      and control as compared to the pre-implementation study. However, certain gaps in
      their KAP need to be given attention; thus continuous education of pet owners
      must be done.

PMID- 30274415
TI  - The 'Influenza' Vaccine Used during the Samoan Pandemic of 1918.
AB  - In 1918, a crude influenza vaccine made from chemically inactivated, mixed
      cultures of respiratory bacteria was widely used prior to the understanding that
      influenza was caused by a virus. Such vaccines contained no viral material and
      probably consisted largely of bacterial endotoxin. The Australian military used
      such a vaccine on Samoa in December 1918 and thought it was valuable. Post hoc
      analyses suggest that the mixed respiratory bacteria vaccine may have actually
      been of some benefit, but the mechanism of such protection is unknown. Although
      such a crude vaccine would not be considered in a modern setting, the rapid use
      of problematic vaccines still remains a risk when new influenza types suddenly
      appear, as in 1976 and 2009.

PMID- 30274416
TI  - Use of Intermittent Preventive Treatment among Pregnant Women in Sub-Saharan
      Africa: Evidence from Malaria Indicator Surveys.
AB  - Uptake of intermittent preventive therapy in pregnancy (IPTp) with sulfadoxine
      pyrimethamine (IPTp-SP) is a clinically-proven method to prevent the adverse
      outcomes of malaria in pregnancy (MiP) for the mother, her foetus, and the
      neonates. The majority of countries in sub-Saharan Africa have introduced IPTp
      policies for pregnant women during the past decade. Nonetheless, progress towards
      improving IPTp coverage remains dismal, with widespread regional and
      socioeconomic disparities in the utilisation of this highly cost-effective
      service. In the present study, our main objective was to measure the prevalence
      of IPTp uptake in selected malaria-endemic countries in sub-Saharan Africa, and
      to investigate the patterns of IPTp uptake among different educational and wealth
      categories adjusted for relevant sociodemographic factors. For this study, cross
      sectional data on 18,603 women aged between 15 and 49 years were collected from
      the Malaria Indicator Surveys (MIS) conducted in Burkina Faso, Ghana, Mali,
      Malawi, Kenya, Nigeria, Sierra Leone, and Uganda. The outcome variable was taking
      three doses of IPTp-SP in the last pregnancy, defined as adequate by the WHO.
      According to the analysis, the overall prevalence of taking three doses of IPTp
      SP in the latest pregnancy was 29.5% (95% CI = 28.2-30.5), with the prevalence
      being highest for Ghana (60%, 95% CI = 57.1-62.8), followed by Kenya (37%, 95% CI
      = 35.3-39.2) and Sierra Leone (31%, 95% CI = 29.2-33.4). Women from non-poor
      households (richer-20.7%, middle-21.2%, richest-18.1%) had a slightly higher
      proportion of taking three doses of IPTp-SP compared with those from poorest
      (19.0%) and poorer (21.1%) households. Regression analysis revealed an inverse
      association between uptake of IPTp-SP and educational level. With regard to
      wealth status, compared with women living in the richest households, those in the
      poorest, poorer, middle, and richer households had significantly higher odds of
      not taking at least three doses of IPTp-SP during their last pregnancy. The
      present study concludes that the prevalence of IPTp-SP is still alarmingly low
      and is significantly associated with individual education and household wealth
      gradient. Apart from the key finding of socioeconomic disparities within
      countries, were the between-country variations that should be regarded as a
      marker of inadequate policy and healthcare system performance in the respective
      countries. More in-depth and longitudinal studies are required to understand the
      barriers to, and preferences of, using IPTp-SP among women from different
      socioeconomic backgrounds.

PMID- 30274417
TI  - Hemophagocytic Lymphohistiocytosis Associated with Scrub Typhus: Systematic
      Review and Comparison between Pediatric and Adult Cases.
AB  - BACKGROUND: Scrub typhus is a mite-borne bacterial infection caused by Orientia
      tsutsugamushi. Hemophagocytic lymphohistiocytosis (HLH) is a potential severe
      complication. Most reported cases of HLH associated with scrub typhus were single
      cases or case series with a small sample sizes. Thus, no clear consensus exists
      on clinical manifestations and differences between pediatric and adult cases of
      this condition. METHODS: a systematic search of English and Japanese articles
      from PubMed, PubMed Central, and Directory of Open Access Journals databases was
      performed from 3 December 2016 to 28 December 2017. The primary outcome was
      mortality in patients with HLH associated with scrub typhus; secondary outcomes
      were differences in clinical symptoms, laboratory findings, and treatment between
      pediatric and adult patients with HLH associated with scrub typhus. RESULTS:
      thirty cases of HLH associated with scrub typhus were identified (age range: 2
      months to 75 years; median age: 21.5 years, male:female ratio, 1:1). Eschar was
      frequently observed in the pediatric group (p = 0.017), whereas acute kidney
      injury was more prevalent in the adult group (p = 0.010). Two patients died of
      intracranial hemorrhage complicated with multiple organ failure; overall
      mortality rate was 6.7%. CONCLUSIONS: HLH associated with scrub typhus could be
      cured with remarkable improvement using single antibiotic therapy in
      approximately half the cases, with the mortality rate being relatively lower than
      that of HLH associated with other secondary causes.

PMID- 30274418
TI  - Melioidosis in Brunei Darussalam.
AB  - Melioidosis continues to be a major health care problem in Brunei Darussalam. The
      age of patients, gender distribution, risk factors, and clinical presentations
      are similar to those reported from other countries in the region. The incidence
      of melioidosis was high during the wet months and in the Temburong district,
      which has the highest annual rainfall. In spite of adequate facilities for
      diagnosis and treatment, the mortality remains high (27%). Women and those
      presenting with septic shock had higher mortality. There is a case for making
      melioidosis a notifiable disease in Brunei Darussalam. Coordinated efforts
      between policy-makers and various stakeholders are required to effectively combat
      the disease.

PMID- 30274420
TI  - Melioidosis in Sri Lanka.
AB  - Until recently, Sri Lanka was not considered a country with endemic melioidosis.
      However, an increasing number of cases is being reported. National surveillance
      for melioidosis was instituted after 2008. A total of 250 culture-positive cases
      was recorded between 2006 and May 2017. Males predominated (71.6%). The age range
      was wide (2-92 years) reflecting a ubiquity of exposure. The majority (201/250,
      80%) lived in rural areas. All provinces were affected. Case load increased
      during the two monsoonal periods (67%). There was representation of every
      population group including farmers (n = 44), housewives (n = 24), school children
      (n = 10), professionals (n = 5), businesspersons (n = 6), white-collar workers (n
      = 10) and blue-collar workers (n = 8). Diabetes was the predominant risk factor
      (n = 163, 65.2%). Clinical presentations included community-acquired sepsis and
      pneumonia, superficial and deep abscesses, and septic arthritis. Mortality was
      20.4% (51/250). A majority (n = 212) of isolates belonged to the YLF (Yersinia
      like fimbrial) clade but 38 were BTFC (B. thailandensis-like flagellum and
      chemotaxis). A total of 108 isolates was genotyped and 46 sequence types (STs)
      were identified, 40 being novel. It is clear that melioidosis is endemic in Sri
      Lanka with a wide geographic and demographic distribution. There is an urgent
      need to extend surveillance of melioidosis to under-resourced parts of the
      country and to populations at high risk.

PMID- 30274419
TI  - Melioidosis in the Lao People's Democratic Republic.
AB  - Melioidosis is clearly highly endemic in Laos, although the disease has only been
      diagnosed regularly in humans (1359 cases) since 1999, and only a single animal
      case has been microbiologically confirmed. Burkholderia pseudomallei is
      extensively and abundantly present in soil and surface water in central and
      southern Laos, but the true distribution of the disease across the country
      remains to be determined. Surveillance is almost non-existent and diagnostic
      microbiology services are not yet well established, whilst awareness of
      melioidosis is low amongst policy-makers, healthcare providers, and the public.
      It is hoped that this situation will improve over the next decade as the country
      rapidly develops, especially as this is likely to be accompanied by a further
      increase in the prevalence of diabetes, meaning that more people in this
      predominantly agricultural population will be at risk of contracting melioidosis.

PMID- 30274421
TI  - A Report from the Cambodia Training Event for Awareness of Melioidosis (C-TEAM),
      October 2017.
AB  - Melioidosis is an endemic infection in Cambodia, a lower middle income SE Asian
      country. Despite more laboratories isolating and identifying Burkholderia
      pseudomallei in recent years, the infection remains under-recognised and under
      diagnosed, particularly in the adult population. Lack of knowledge about the
      disease and lack of utilization of microbiology laboratories contributes to this,
      along with laboratory capacity issues. Treatment costs often hamper optimal
      management. In response to these issues, a national one-health training event was
      held in October 2017 to raise awareness of the disease amongst clinical,
      laboratory, and public health professionals. The meeting format, findings, and
      outcomes are described here.

PMID- 30274422
TI  - Melioidosis in Malaysia: Incidence, Clinical Challenges, and Advances in
      Understanding Pathogenesis.
AB  - Malaysia is an endemic hot spot for melioidosis; however, a comprehensive picture
      of the burden of disease, clinical presentations, and challenges faced in
      diagnosis and treatment of melioidosis is not available. This review provides a
      nonexhaustive overview of epidemiological data, clinical studies, risk factors,
      and mortality rates from available literature and case reports. Clinical patterns
      of melioidosis are generally consistent with those from South and Southeast Asia
      in terms of common primary presentations with diabetes as a major risk factor.
      Early diagnosis and appropriate management of Malaysian patients is a key
      limiting factor, which needs to be addressed to reduce serious complications and
      high mortality and recurrence rates. Promoting awareness among the local
      healthcare personnel is crucial to improving diagnostics and early treatment, as
      well as educating the Malaysian public on disease symptoms and risk factors. A
      further matter of urgency is the need to make this a notifiable disease and the
      establishment of a national melioidosis registry. We also highlight local studies
      on the causative agent, Burkholderia pseudomallei, with regards to bacteriology
      and identification of virulence factors as well as findings from host-pathogen
      interaction studies. Collectively, these studies have uncovered new correlations
      and insights for further understanding of the disease.

PMID- 30274423
TI  - Transmission Modes of Melioidosis in Taiwan.
AB  - In Taiwan, melioidosis is an emerging disease that suddenly increased in the Er
      Ren River Basin, beginning in 2005 and in the Zoynan region during 2008-2012,
      following a typhoon. Additionally, the disease sporadically increased in a
      geography-dependent manner in 2016. Subcutaneous inoculation, ingestion, and the
      inhalation of soil or water contaminated with Burkholderia pseudomallei are
      recognized as the transmission modes of melioidosis. The appearance of
      environmental B. pseudomallei positivity in northern, central and southern Taiwan
      is associated with disease prevalence (cases/population: 0.03/100,000 in the
      northern region, 0.29/100,000 in the central region and 1.98/100,000 in the
      southern region). However, melioidosis-clustered areas are confined to 5 to 7.5
      km2 hot spots containing high-density populations, but B. pseudomallei
      contaminated environments are located >5 km northwestern of the periphery of
      these hot spots. The observation that the concentration of B. pseudomallei
      specific DNA in aerosols was positively correlated with the incidence of
      melioidosis and the appearance of a northwesterly wind in a hot spot indicated
      that airborne transmission had occurred in Taiwan. Moreover, the isolation rate
      in the superficial layers of a contaminated crop field in the northwest was
      correlated with PCR positivity in aerosols collected from the southeast over a
      two-year period. The genotype ST58 was identified by multilocus sequence typing
      in human and aerosol isolates. The genotype ST1001 has increased in prevalence
      but has been sporadically distributed elsewhere since 2016. These data indicate
      the transmission modes and environmental foci that support the dissemination of
      melioidosis are changing in Taiwan.

PMID- 30274425
TI  - Melioidosis in Myanmar.
AB  - Sporadic cases of melioidosis have been diagnosed in Myanmar since the disease
      was first described in Yangon in 1911. Published and unpublished cases are
      summarized here, along with results from environmental and serosurveys. A total
      of 298 cases have been reported from seven states or regions between 1911 and
      2018, with the majority of these occurring before 1949. Findings from soil
      surveys confirm the presence of Burkholderia pseudomallei in the environment in
      all three regions examined. The true epidemiology of the disease in Myanmar is
      unknown. Important factors contributing to the current gaps in knowledge are lack
      of awareness among clinicians and insufficient laboratory diagnostic capacity in
      many parts of the country. This is likely to have led to substantial under
      reporting.

PMID- 30274426
TI  - Spotted Fever Rickettsiosis in a Wildlife Researcher in Sabah, Malaysia: A Case
      Study.
AB  - We present evidence for a case of spotted fever rickettsiosis with severe
      complications in a young adult male. Although spotted fever group rickettsiae
      (SFGR) have been reported as the most prevalent cause of rickettsiosis in rural
      areas of Sabah, Malaysia since the 1980s, this is the first detailed case report
      of suspected SFGR in the state. Current data on the prevalence, type, and
      thorough clinical reports on complications of SFGR and other rickettsioses in
      Sabah is lacking and required to raise the awareness of such diseases. There is a
      need to emphasize the screening of rickettsioses to medical personnel and to
      encourage the use of appropriate antibiotics as early treatment for nonspecific
      febrile illnesses in this region. Suspected rickettsioses need to be considered
      as one of the differential diagnoses for patients presenting with acute febrile
      illness for laboratory investigations, and early treatment instituted.

PMID- 30274424
TI  - Melioidosis: An Australian Perspective.
AB  - Burkholderia pseudomallei is endemic in northern Australia, with cases of
      melioidosis most commonly occurring during the wet season in individuals with
      diabetes, hazardous alcohol use, and chronic kidney disease. Pneumonia is the
      most common presentation and the majority of patients are bacteraemic-however,
      infection may involve almost any organ, with the skin and soft tissues,
      genitourinary system, visceral organs, and bone and joints affected most
      commonly. Central nervous system involvement is rarer, but has a high
      attributable mortality. Increased awareness of the disease amongst healthcare
      providers, ready access to appropriate antibiotic therapy and high-quality
      intensive care services has resulted in a sharp decline in the case fatality rate
      over the last 20 years. Further improvement in clinical outcomes will require a
      greater understanding of the disease's pathophysiology, its optimal management,
      and more effective strategies for its prevention.

PMID- 30274427
TI  - Melioidosis in the Western Indian Ocean and the Importance of Improving
      Diagnosis, Surveillance, and Molecular Typing.
AB  - Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an infectious
      disease of humans or animals, and the specific environmental conditions that are
      present in western Indian Ocean islands are particularly suitable for the
      establishment/survival of B. pseudomallei. Indeed, an increasing number of new
      cases have been reported in this region (Madagascar, Mauritius, Reunion (France),
      and Seychelles, except Comoros and Mayotte (France)), and are described in this
      review. Our review clearly points out that further studies are needed in order to
      investigate the real incidence and burden of melioidosis in the western Indian
      Ocean and especially Madagascar, since it is likely to be higher than currently
      reported. Thus, research and surveillance priorities were recommended (i) to
      improve awareness of melioidosis in the population and among clinicians; (ii) to
      improve diagnostics, in order to provide rapid and effective treatment; (iii) to
      implement a surveillance and reporting system in the western Indian Ocean; and
      (iv) to investigate the presence of B. pseudomallei in environmental samples,
      since we have demonstrated its presence in soil samples originating from the yard
      of a Madagascan case.

PMID- 30274430
TI  - A Tool for Assessment of Animal Health Laboratory Safety and Biosecurity: The
      Safety Module of the Food and Agriculture Organization's Laboratory Mapping Tool.
AB  - The Laboratory Management Tool (LMT) is a standardized spreadsheet-based
      assessment tool developed to help support national, regional, and global efforts
      to maintain an effective network of animal health and veterinary public health
      laboratories. The safety and biosecurity module of the LMT (LMT-S) includes 98
      measures covering administrative, operational, engineering, and personal
      protective equipment practices used to provide laboratory safety and biosecurity.
      Performance aspects of laboratory infrastructure and technical compliance
      considered fundamental for ensuring that a laboratory is able to appropriately
      function in a safe and biosecure manner are systematically queried and scored for
      compliance on a four-point scale providing for a semi-quantitative assessment.
      Data collected is used to generate graphs and tables mapping levels of compliance
      with international standards and good practices, as well as for documenting
      progress over time. The LMT-S was employed by trained auditors in 34 laboratories
      located in 19 countries between 2015 and 2017. The tool is intended to help
      standardize animal health laboratory assessments, document compliance with
      recognized laboratory safety and biosecurity measures, serve as a self-help and
      training tool, and assist global laboratory development efforts by providing an
      accurate measurement of laboratory safety and biosecurity at local, national, and
      regional levels.

PMID- 30274428
TI  - Melioidosis in Singapore: Clinical, Veterinary, and Environmental Perspectives.
AB  - Melioidosis is a notifiable infectious disease registered with the Ministry of
      Health (MOH) and Agri-Food & Veterinary Authority (AVA), Singapore. From a
      clinical perspective, increased awareness of the disease has led to early
      detection and treatment initiation, thus resulting in decreasing mortality rates
      in recent years. However, the disease still poses a threat to local pet, zoo and
      farm animals, where early diagnosis is a challenge. The lack of routine
      environmental surveillance studies also makes prevention of the disease in
      animals difficult. To date, there have been no reports that provide a complete
      picture of how the disease impacts the local human and animal populations in
      Singapore. Information on the distribution of Burkholderia pseudomallei in the
      environment is also lacking. The aim of this review is to provide a comprehensive
      overview of both published and unpublished clinical, veterinary and environmental
      studies on melioidosis in Singapore to achieve better awareness and management of
      the disease.

PMID- 30274429
TI  - Emergence of Melioidosis in Indonesia and Today's Challenges.
AB  - A recent modeling study estimated that there could be as many as 20,000 human
      melioidosis cases per year in Indonesia, with around 10,000 potential deaths
      annually. Nonetheless, the true burden of melioidosis in Indonesia is still
      unknown. The Indonesia Melioidosis Network was formed during the first
      melioidosis workshop in 2017. Here, we reviewed 101 melioidosis cases (99 human
      and two animal cases) previously reported and described an additional 45 human
      melioidosis cases. All 146 culture-confirmed cases were found in Sumatra (n =
      15), Java (n = 104), Kalimantan (n = 15), Sulawesi (n = 11) and Nusa Tenggara (n
      = 1). Misidentification of Burkholderia pseudomallei was not uncommon, and most
      cases were only recently identified. We also evaluated clinical manifestations
      and outcome of recent culture-confirmed cases between 2012 and 2017 (n = 42).
      Overall, 15 (36%) cases were children (age <15 years) and 27 (64%) were adults
      (age >=15 years). The overall mortality was 43% (18/42). We conducted a survey
      and found that 57% (327/548) of healthcare workers had never heard of
      melioidosis. In conclusion, melioidosis is endemic throughout Indonesia and
      associated with high mortality. We propose that top priorities are increasing
      awareness of melioidosis amongst all healthcare workers, increasing the use of
      bacterial culture, and ensuring accurate identification of B. pseudomalleiand
      diagnosis of melioidosis.

PMID- 30274431
TI  - Melioidosis in Papua New Guinea and Oceania.
AB  - Melioidosis has only been sporadically reported throughout Melanesia and the
      Pacific region since the first report from Guam in 1946; therefore, its
      contribution to the disease burden in this region is largely unknown. However,
      the outcome of a small number of active surveillance programs, serological
      surveys, and presumptive imported cases identified elsewhere provide an insight
      into its epidemiology and potential significance throughout the region. Both
      clinical cases and environmental reservoirs have been described from the rural
      district of Balimo in the Western Province of Papua New Guinea and from the
      Northern Province of New Caledonia. In both these locations the incidence of
      disease is similar to that described in tropical Australia and Burkholderia
      pseudomallei isolates are also phylogenetically linked to Australian isolates.
      Serological evidence and presumptive imported cases identified elsewhere suggest
      that melioidosis exists in other countries throughout the Pacific. However, the
      lack of laboratory facilities and clinical awareness, and the burden of other
      infections of public health importance such as tuberculosis, contribute to the
      under-recognition of melioidosis in this region.

PMID- 30274432
TI  - Salmonella enterica Serovar Typhi: An Unusual Cause of Infective Endocarditis.
AB  - While typhoid fever is a common infection, Salmonella enterica serovar Typhi is a
      rare cause of endocarditis. We describe the case of a 20-year-old male who was
      treated for a primary episode of microbiologically-confirmed typhoid fever. He
      presented six weeks post-discharge with fever and lethargy. S. Typhi was again
      identified in blood cultures, and echocardiography identified a mitral valve
      lesion. Our case suggests that a relapse of typhoid should prompt further
      investigation for a deep-seated infection, including consideration of
      echocardiographic evaluation to rule out infective endocarditis.

PMID- 30274433
TI  - A Review of Laboratory-Acquired Infections in the Asia-Pacific: Understanding
      Risk and the Need for Improved Biosafety for Veterinary and Zoonotic Diseases.
AB  - A rapid review was performed to determine (1) the number and causes of reported
      laboratory-acquired infections (LAI) in the Asia-Pacific region; (2) their
      significance and threat to the community; (3) the primary risk factors associated
      with LAIs; (4) the consequences in the event of a LAI or pathogen escape; and (5)
      to make general recommendations regarding biosafety practices for diagnosis and
      research in the Asia-Pacific region. A search for LAI and zoonoses in the Asia
      Pacific region using online search engines revealed a relatively low number of
      reports. Only 27 LAI reports were published between 1982 and 2016. The most
      common pathogens associated with LAIs were dengue virus, Arthroderma spp.,
      Brucella spp., Mycobacterium spp., Rickettsia spp., and Shigella spp. Seventy
      eight percent (21 out of 27 LAI reports) occurred in high-income countries (i.e.,
      Australia, Japan, South Korea, Singapore, and Taiwan) where laboratories were
      likely to comply with international biosafety standards. Two upper-middle income
      countries (China (2), and Malaysia (2)) and one lower-middle income country
      (India (2)) reported LAI incidents. The majority of the reports (fifty-two
      percent (14/27)) of LAIs occurred in research laboratories. Five LAI reports were
      from clinical or diagnostic laboratories that are considered at the frontier for
      zoonotic disease detection. Governments and laboratories in the Asia-Pacific
      region should be encouraged to report LAI cases as it provides a useful tool to
      monitor unintended release of zoonotic pathogens and to further improve
      laboratory biosafety. Non-reporting of LAI events could pose a risk of disease
      transmission from infected laboratory staff to communities and the environment.
      The international community has an important and continuing role to play in
      supporting laboratories in the Asia-Pacific region to ensure that they maintain
      the safe working environment for the staff and their families, and the wider
      community.

PMID- 30274434
TI  - Involvement of Hookworm Co-Infection in the Pathogenesis and Progression of
      Podoconiosis: Possible Immunological Mechanism.
AB  - Podoconiosis is an endemic, non-infectious, geochemical and non-filarial
      inflammatory cause of tropical elephantiasis. The immunology of podoconiosis is
      not yet expressly understood. In spite of this, co-infection and co-morbidity
      with the infectious, soil-transmitted hookworm disease that causes iron
      deficiency anemia has been found to be predominant among affected individuals
      living in co-endemic settings, thus creating a more complex immunological
      interplay that still has not been investigated. Although deworming and iron-rich
      nutrient supplementation have been suggested in podoconiosis patients living
      under resource-poor conditions, and it is thought that hookworm infection may
      help to suppress inflammatory responses, the undisputed link that exists between
      a non-infectious and an infectious disease may create a scenario whereby during a
      co-infection, treatment of one exacerbates the other disease condition or is
      dampened by the debilitation caused by the other. In this paper, we elaborate on
      the immunopathogenesis of podoconiosis and examine the possible immunological
      dynamics of hookworm co-infection in the immunopathology of podoconiosis, with a
      view toward improved management of the disease that will facilitate its feasible
      elimination.

PMID- 30274435
TI  - Melioidosis in Vietnam: Recently Improved Recognition but still an Uncertain
      Disease Burden after Almost a Century of Reporting.
AB  - The first cases of human melioidosis were described in Vietnam in the 1920s,
      almost a century ago. It was in Vietnam in the thirties that the saprophytic
      nature of B. pseudomallei was first recognized. Although a significant number of
      French and U.S. soldiers acquired the disease during the Vietnam wars, indigenous
      cases in the Vietnamese population were only sporadically reported over many
      decades. After reunification in 1975, only two retrospective studies reported
      relatively small numbers of indigenous cases from single tertiary care hospitals
      located in the biggest cities in the South and the North, respectively. Studies
      from provincial hospitals throughout the country were missing until the Research
      Network on Melioidosis and Burkholderia pseudomallei (RENOMAB) project started in
      2014. From then on seminars, workshops, and national scientific conferences on
      melioidosis have been conducted to raise awareness among physicians and clinical
      laboratory staff. This led to the recognition of a significant number of cases in
      at least 36 hospitals in 26 provinces and cities throughout Vietnam. Although a
      widespread distribution of melioidosis has now been documented, there are still
      challenges to understand the true epidemiology of the disease. Establishment of
      national guidelines for diagnosis, management, and reporting of the disease
      together with more investigations on animal melioidosis, genomic diversity of B.
      pseudomallei and its environmental distribution are required.

PMID- 30274436
TI  - Melioidosis in Bangladesh: A Clinical and Epidemiological Analysis of Culture
      Confirmed Cases.
AB  - Melioidosis is known to occur in Bangladesh, but there are few reports about the
      condition in the published international literature. We set out to review all
      known cases of melioidosis in the country to date, using both retrospective and
      prospective data. A web-based literature search was conducted to identify all
      published case reports, original articles and conference abstracts. Cases were
      also included from a prospective study conducted in 2017. Fifty-one cases were
      identified between 1961 and 2017. Cases have been reported from sixteen out of
      the 64 districts of Bangladesh. The median age of the patients at presentation
      was 45 years (IQR 37-52), with a significant male (77%) predominance. Many
      patients (14/39; 36%) were farmers and 83% had diabetes mellitus. A skin/soft
      tissue abscess was the most common primary clinical presentation (13/49; 27%),
      followed by septic arthritis (10/49; 20%), pneumonia, and a deep-seated
      abscess/organ abscess (7/49; 14%). The major challenges to the diagnosis and
      treatment of melioidosis in Bangladesh are the lack of resources and the lack of
      awareness of melioidosis. Capacity development programs are urgently required to
      define the burden of disease and to tackle the mortality rates.

PMID- 30274437
TI  - Improving Water, Sanitation and Hygiene Practices, and Housing Quality to Prevent
      Diarrhea among Under-Five Children in Nigeria.
AB  - Sub-Saharan Africa as a region accounts for the bulk of the global under-five
      mortality rate, to which diarrhea is major contributor. Millions of children die
      from diarrheal diseases each year and those who survive often do so facing
      suboptimal growth. Preventing the common pathways of transmission for diarrhea
      causing pathogens, including improved water, sanitation, and hygiene (WASH) are
      regarded as the most cost-effective measures for tackling this life-threatening
      disease. This study aimed to quantitatively assess the quality of living
      arrangement and access to WASH, and their impact on diarrheal outcomes among
      under-five children in Nigeria. Methods: Data were collected from the 2013
      Nigeria Demographic and Health survey (NDHS). Study participants included 28,596
      mother-child pairs. Household construction material for wall, floor, and ceiling,
      access to electricity, and improved water and toilet, were included as the main
      explanatory variables. Data were analyzed using descriptive and multivariable
      regression methods. Results: The prevalence of diarrhea was 11.3% (95% CI = 10.2
      12.6), with the rate being markedly higher in rural (67.3%) as compared to urban
      areas (32.7%). In the regression analysis, lacking access to improved toilet and
      water facilities were associated with 14% and 16% higher odds, respectively, of
      suffering from diarrhea as compared to those who had improved access. Conclusion:
      There is evidence of a weak, but statistically significant, relationship between
      the quality of living environment, including water and sanitation facilities, and
      diarrhea among under-five children in Nigeria. The study concludes that investing
      in living conditions and WASH may have potential benefits for child mortality
      prevention programs in the country.

PMID- 30274438
TI  - Recent Advances in Next Generation Snakebite Antivenoms.
AB  - With the inclusion of snakebite envenoming on the World Health Organization's
      list of Neglected Tropical Diseases, an incentive has been established to promote
      research and development effort in novel snakebite antivenom therapies. Various
      technological approaches are being pursued by different research groups,
      including the use of small molecule inhibitors against enzymatic toxins as well
      as peptide- and oligonucleotide-based aptamers and antibody-based biotherapeutics
      against both enzymatic and non-enzymatic toxins. In this article, the most recent
      advances in these fields are presented, and the advantages, disadvantages, and
      feasibility of using different toxin-neutralizing molecules are reviewed.
      Particular focus within small molecules is directed towards the inhibitors
      varespladib, batimastat, and marimastat, while in the field of antibody-based
      therapies, novel recombinant polyclonal plantivenom technology is discussed.

PMID- 30274440
TI  - Towards TB Elimination in Aotearoa/New Zealand: Key Informant Insights on the
      Determinants of TB among African Migrants.
AB  - Migrants living in low incidence countries, including New Zealand (NZ), are
      disproportionately affected by tuberculosis (TB). This foreign-born group poses
      important challenges to achieving the national TB elimination targets. Thus, the
      aim of this study was to contribute to the understandingof factors that influence
      the incidence of TB among African migrants living in NZ. We employed a semi
      structured interview approach to explore the perceptions of NZ-based African
      community leaders, health professionals and a non-governmental TB support
      organisation about the wider determinants of TB. The findings, though not
      completely generalizable, suggest that many NZ-based Africans endure a difficult
      process of integration, perceive themselves as least susceptible to TB and have
      low awareness about available health services. Furthermore, the cost of general
      practitioner (GP) services, mistrust of health professionals, TB stigma and the
      NZ immigration policy were indicated as important barriers to TB services.
      Strategies to address TB among migrants must therefore be more holistic and not
      be centred on a fragmented approach that overemphasises the biomedical
      approaches, as the incidence of TB is more likely the outcome of a complex
      interplay of several underlying factors.

PMID- 30274439
TI  - A Comparative Assessment of Epidemiologically Different Cutaneous Leishmaniasis
      Outbreaks in Madrid, Spain and Tolima, Colombia: An Estimation of the
      Reproduction Number via a Mathematical Model.
AB  - Leishmaniasis is a neglected tropical disease caused by the Leishmania parasite
      and transmitted by the Phlebotominae subfamily of sandflies, which infects humans
      and other mammals. Clinical manifestations of the disease include cutaneous
      leishmaniasis (CL), mucocutaneous leishmaniasis (MCL) and visceral leishmaniasis
      (VL) with a majority (more than three-quarters) of worldwide cases being CL.
      There are a number of risk factors for CL, such as the presence of multiple
      reservoirs, the movement of individuals, inequality, and social determinants of
      health. However, studies related to the role of these factors in the dynamics of
      CL have been limited. In this work, we (i) develop and analyze a vector-borne
      epidemic model to study the dynamics of CL in two ecologically distinct CL
      affected regions-Madrid, Spain and Tolima, Colombia; (ii) derived three different
      methods for the estimation of model parameters by reducing the dimension of the
      systems; (iii) estimated reproduction numbers for the 2010 outbreak in Madrid and
      the 2016 outbreak in Tolima; and (iv) compared the transmission potential of the
      two economically-different regions and provided different epidemiological metrics
      that can be derived (and used for evaluating an outbreak), once R0 is known and
      additional data are available. On average, Spain has reported only a few hundred
      CL cases annually, but in the course of the outbreak during 2009-2012, a much
      higher number of cases than expected were reported and that too in the single
      city of Madrid. Cases in humans were accompanied by sharp increase in infections
      among domestic dogs, the natural reservoir of CL. On the other hand, CL has
      reemerged in Colombia primarily during the last decade, because of the frequent
      movement of military personnel to domestic regions from forested areas, where
      they have increased exposure to vectors. In 2016, Tolima saw an unexpectedly high
      number of cases leading to two successive outbreaks. On comparing, we estimated
      reproduction number of the Madrid outbreak to be 3.1 (with range of 2.8-3.9),
      which was much higher than reproduction number estimates of the Tolima first
      outbreak 1.2 (with range of 1.1-1.3), and the estimate for the second outbreak in
      Tolima of 1.019 (with range of 1.018-1.021). This suggests that the epidemic
      outbreak in Madrid was much more severe than the Tolima outbreak, even though
      Madrid was economically better-off compared to Tolima. It indicates a potential
      relationship between urban development and increasing health disparities.

PMID- 30274441
TI  - First Aid and Pre-Hospital Management of Venomous Snakebites.
AB  - BACKGROUND: Antivenom is the definitive treatment for venomous snakebites, but is
      expensive and not available in many rural and poorly developed regions. Timely
      transportation to facilities that stock and administer antivenom may not be
      available in rural areas with poorly developed emergency medical services. These
      factors have led to consideration of measures to delay onset of toxicity or
      alternatives to antivenom therapy. METHODS: PubMed searches were conducted for
      articles on snakebite treatment, or that contained first aid, emergency medical
      services, tourniquets, pressure immobilization bandages, suction devices, and
      lymphatic flow inhibitors. RESULTS: The reviewed articles describe how venoms
      spread after a venomous snakebite on an extremity, list the proposed first aid
      measures for delaying the spread of venoms, and evaluate the scientific studies
      that support or refute methods of snakebite first aid. The recommendations for
      field treatment of venomous snakebites will be discussed. CONCLUSIONS: The
      evidence suggests that pressure immobilization bandages and related strategies
      are the best interventions to delay onset of systemic toxicity from venomous
      snakebites but may increase local toxicity for venoms that destroy tissue at the
      site of the bite, so their use should be individualized to the circumstances and
      nature of the venom.

PMID- 30274442
TI  - Strongyloides stercoralis Hyperinfection in an HIV-Infected Patient Successfully
      Treated with Subcutaneous Ivermectin.
AB  - A 39-year-old Ethiopian HIV-positive man with peripheral T-cell lymphoma
      developed Strongyloides stercoralis hyperinfection. The patient was initially
      treated with oral ivermectin for three weeks without response, most likely due to
      malabsorption because of concomitant paralytic ileus. Given the persistence of
      larvae in the body fluids, the worsening respiratory status and clinical
      malabsorption, veterinary parenteral formulation of ivermectin was administered.
      The very high plasma concentration of ivermectin achieved in the patient after
      parenteral administration led to a rapid improvement in his clinical condition
      and rapid disappearance of the parasite from biological samples, without any
      adverse reaction.

PMID- 30274444
TI  - A Community-Directed Integrated Strongyloides Control Program in Queensland,
      Australia.
AB  - This paper describes two phases of a community-directed intervention to address
      strongyloidiasis in the remote Aboriginal community of Woorabinda in central
      Queensland, Australia. The first phase provides the narrative of a community
      driven 'treat-and-test' mass drug administration (MDA) intervention that was co
      designed by the Community Health Service and the community. The second phase is a
      description of the re-engagement of the community in order to disseminate the key
      factors for success in the previous MDA for Strongyloides stercoralis, as this
      information was not shared or captured in the first phase. During the first phase
      in 2004, there was a high prevalence of strongyloidiasis (12% faecal examination,
      30% serology; n = 944 community members tested) that resulted in increased
      morbidity and at least one death in the community. Between 2004-2005, the
      community worked in partnership with the Community Health Service to implement a
      S. stercoralis control program, where all of the residents were treated with oral
      ivermectin, and repeat doses were given for those with positive S. stercoralis
      serology. The community also developed their own health promotion campaign using
      locally-made resources targeting relevant environmental health problems and
      concerns. Ninety-two percent of the community residents participated in the
      program, and the prevalence of strongyloidiasis at the time of the 'treat-and
      test' intervention was 16.6% [95% confidence interval 14.2-19.3]. The cure rate
      after two doses of ivermectin was 79.8%, based on pre-serology and post-serology
      tests. The purpose of this paper is to highlight the importance of local
      Aboriginal leadership and governance and a high level of community involvement in
      this successful mass drug administration program to address S. stercoralis. The
      commitment required of these leaders was demanding, and involved intense work
      over a period of several months. Apart from controlling strongyloidiasis, the
      community also takes pride in having developed and implemented this program. This
      appears to be the first community-directed S. stercoralis control program in
      Australia, and is an important part of the national story of controlling
      infectious diseases in Indigenous communities.

PMID- 30274443
TI  - Echinococcus Granulosus Infection in Two Free-Ranging Lumholtz's Tree-Kangaroo
      (Dendrolagus lumholtzi) from the Atherton Tablelands, Queensland.
AB  - Infection with the larval stage of the cestode, Echinococcus granulosus sensu
      lato (s.l.), causes hydatid disease (hydatidosis) in a range of hosts, including
      macropods and other marsupials, cattle, and humans. Wild macropods are an
      important sylvatic reservoir for the life cycle of E. granulosus (s.l.) in
      Australia, and so provide a conduit for transmission of hydatid disease to
      domestic animals and humans. Two Lumholtz's tree-kangaroos (Dendrolagus
      lumholtzi) from the Atherton Tablelands of Far North Queensland were recently
      found to have hydatid cysts in both liver and lung tissues. Tree-kangaroos may
      travel across the ground between patches of forest but are primarily arboreal
      leaf-eating macropods. The finding of hydatid cysts in an arboreal folivore may
      indicate that the area has a high level of contamination with eggs of E.
      granulosus (s.l.). This finding may be of significance to human health as well as
      indicating the need for further investigation into the prevalence of hydatid
      disease in domestic stock, wildlife and humans living in this rapidly urbanizing
      region.

PMID- 30274445
TI  - Murray Valley Encephalitis Virus: An Ongoing Cause of Encephalitis in Australia's
      North.
AB  - Murray Valley encephalitis virus (MVEV) is a mosquito-borne virus endemic to
      Australia and New Guinea. Encephalitis due to MVEV is potentially devastating,
      and no therapeutic interventions of proven value exist. Prevention relies largely
      on personal protective measures against mosquito bites. We present a case of MVEV
      encephalitis with a favourable outcome following intensive care management and
      prolonged rehabilitation, and the epidemiological features of a further 21 cases
      notified to the health department of Australia's Northern Territory. As cases
      occur in travellers, and epidemics occur sporadically in south-eastern Australia,
      clinicians across Australia and further abroad should be familiar with the
      disease and its diagnosis and management.

PMID- 30274446
TI  - The Health Effects of Strongyloidiasis on Pregnant Women and Children: A
      Systematic Literature Review.
AB  - Strongyloidiasis is a helminth infection that remains under-researched despite
      its ability to cause significant illness. Women and children may be at particular
      risk of health consequences from this parasite. This systematic literature review
      aims to examine research on the long-term health effects that strongyloidiasis
      has in pregnant women and children. We conducted a structured search using
      multiple databases to collect all primary studies discussing health effects of
      strongyloidiasis in the aforementioned groups. The review included 20 results: 16
      primary studies and four case reports. The methodological quality of studies was
      substandard, and there was substantial heterogeneity to the statistical analysis
      and outcomes assessed in the literature. Statistically significant associations
      were found between strongyloidiasis and low birth weight, as well as wasting. No
      links were found between strongyloidiasis and anaemia. Due to testing methods
      used in the studies, the prevalence of Strongyloides stercoralis in these studies
      was probably under-estimated. Current research is suggestive that
      strongyloidiasis has long-term adverse health effects on the offspring of
      infected mothers and in chronically-infected children. Data analysis was hindered
      by both methodological and statistical flaws, and as such, reliable conclusions
      regarding the health impacts could not be formed.

PMID- 30274448
TI  - Immunisation Rates of Medical Students at a Tropical Queensland University.
AB  - Although medical students are at risk of contracting and transmitting
      communicable diseases, previous studies have demonstrated sub-optimal medical
      student immunity. The objective of this research was to determine the documented
      immunity of medical students at James Cook University to important vaccine
      preventable diseases. An anonymous online survey was administered thrice in 2014,
      using questions with categories of immunity to determine documented evidence of
      immunity, as well as closed-ended questions about attitudes towards the
      importance of vaccination. Of the 1158 medical students targeted via survey, 289
      responses were included in the study (response rate 25%), of which 19 (6.6%) had
      documented evidence of immunity to all of the vaccine-preventable diseases
      surveyed. Proof of immunity was 38.4% for seasonal influenza, 47.1% for
      pertussis, 52.2% for measles, 38.8% for varicella, 43.7% for hepatitis A, and
      95.1% for hepatitis B (the only mandatory vaccination for this population). The
      vast majority of students agreed on the importance of vaccination for personal
      protection (98.3%) and patient protection (95.9%). In conclusion, medical
      students have sub-optimal evidence of immunity to important vaccine-preventable
      diseases. Student attitudes regarding the importance of occupational vaccination
      are inconsistent with their level of immunity. The findings of this study were
      used to prompt health service and educational providers to consider their duty of
      care to manage the serious risks posed by occupational communicable diseases.

PMID- 30274447
TI  - Melioidosis in South Asia (India, Nepal, Pakistan, Bhutan and Afghanistan).
AB  - Despite the fact that South Asia is predicted to have the highest number of cases
      worldwide, melioidosis is a little-known entity in South Asian countries. It has
      never been heard of by the majority of doctors and has as yet failed to gain the
      attention of national Ministries of Health and country offices of the World
      Health Organization (WHO). Although a few centers are diagnosing increasing
      numbers of cases, and the mortality documented from these institutions is
      relatively high (nearly 20%), the true burden of the disease remains unknown. In
      India, most cases have been reported from southwestern coastal Karnataka and
      northeastern Tamil Nadu, although this probably simply reflects the presence of
      centers of excellence and researchers with an interest in the disease. As
      elsewhere, the majority of cases have type 2 diabetes mellitus and occupational
      exposure to the environment. Most present with community-acquired pneumonia
      and/or bacteremia, especially during heavy rainfall. The high seropositivity rate
      (29%) in Karnataka and isolation of B. pseudomallei from the environment in Tamil
      Nadu and Kerala confirm India as melioidosis-endemic, although the full extent of
      the distribution of the organism across the country is unknown. There are limited
      molecular epidemiological data, but, thus far, the majority of Indian isolates
      have appeared distinct from those from South East Asia and Australia. Among other
      South Asian countries, Sri Lanka and Bangladesh are known to be melioidosis
      endemic, but there are no cases that have conclusively proved to have been
      acquired in Nepal, Bhutan, Afghanistan or Pakistan. There are no surveillance
      systems in place for melioidosis in South Asian countries. However, over the past
      two years, researchers at the Center for Emerging and Tropical Diseases of
      Kasturba Medical College, University of Manipal, have established the Indian
      Melioidosis Research Forum (IMRF), held the first South Asian Melioidosis
      Congress, and have been working to connect researchers, microbiologists and
      physicians in India and elsewhere in South Asia to raise awareness through
      training initiatives, the media, workshops, and conferences, with the hope that
      more patients with melioidosis will be diagnosed and treated appropriately.
      However, much more work needs to be done before we will know the true burden and
      distribution of melioidosis across South Asia.

PMID- 30274449
TI  - The Unique Life Cycle of Strongyloides stercoralis and Implications for Public
      Health Action.
AB  - Strongyloides stercoralis has one of the most complex life cycles of the human
      infecting nematodes. A common misconception in medical and public health
      professions is that S. stercoralis in its biology is akin to other intestinal
      nematodes, such as the hookworms. Despite original evidence provided by medical
      and veterinary research about this unique helminth, many assumptions have entered
      the scientific literature. This helminth is set apart from others that commonly
      affect humans by (a) the internal autoinfective cycle with autoinfective larvae
      randomly migrating through tissue, parthenogenesis, and the potential for
      lifelong infection in the host, the profound pathology occurring in
      hyperinfection and systemic manifestations of strongyloidiasis, and (b) a limited
      external cycle with a single generation of free-living adults. This paper aims to
      review and discuss original research on the unique life cycle of S. stercoralis
      that distinguishes it from other helminths and highlight areas where increased
      understanding of the parasite's biology might lead to improved public health
      prevention and control strategies.

PMID- 30274450
TI  - Diagnostic Performance of Kato Katz Technique and Point-of-Care Circulating
      Cathodic Antigen Rapid Test in Diagnosing Schistosoma mansoni Infection in HIV-1
      Co-Infected Adults on the Shoreline of Lake Victoria, Tanzania.
AB  - BACKGROUND: The diagnostic performance of the Kato Katz (KK) technique and the
      point-of-care circulating cathodic antigen (POC-CCA) test in detecting S. mansoni
      infection in the presence of the human immunodeficiency virus-1 (HIV-1) infection
      has remained inconclusive. The present cross-sectional survey compared the
      diagnostic performance of the KK technique and the POC-CCA test in diagnosing S.
      mansoni infection in an adult population co-infected with HIV-1 in northwestern
      Tanzania. METHODS: Single urine and stool samples from 979 adults were screened
      for S. mansoni infection using both the KK technique and POC-CCA tests. To
      compare the performance of the two diagnostic tests a combined artificial gold
      standard was created, based on either an egg-positive KK technique or a POC-CCA
      positive test. RESULTS: Based on the KK technique, the prevalence of S. mansoni
      was 47.3% (463/979, 95% CI: 44.2-50.4), as compared to 60.5% by the POC-CCA test
      (592/979; 95% CI: 57.4-63.5). The overall sensitivity and specificity of the POC
      CCA test were 92.5% (95% CI: 89.4-94.9) and 73.3% (95% CI: 69.6-76.8),
      respectively. In the HIV-1 seropositive group, the sensitivity and specificity of
      the POC-CCA test were 78.1% (95% CI: 60.0-90.7) and 45.9% (95% CI: 35.8-56.3).
      Using a combined gold standard, the sensitivity of the POC-CCA test increased to
      >90% in both subgroups whereas that of the KK technique in the HIV-1 seropositive
      group was low (49.5%; 95% CI: 39.6-59.5). CONCLUSION: In the presence of HIV-1 co
      infection, the KK technique attained a very low sensitivity. The POC-CCA test
      offers the best option for the rapid screening of S. mansoni infection in
      communities with a high prevalence of HIV-1 infection.

PMID- 30274451
TI  - The Convergence of High-Consequence Livestock and Human Pathogen Research and
      Development: A Paradox of Zoonotic Disease.
AB  - The World Health Organization (WHO) estimates that zoonotic diseases transmitted
      from animals to humans account for 75 percent of new and emerging infectious
      diseases. Globally, high-consequence pathogens that impact livestock and have the
      potential for human transmission create research paradoxes and operational
      challenges for the high-containment laboratories that conduct work with them.
      These specialized facilities are required for conducting all phases of research
      on high-consequence pathogens (basic, applied, and translational) with an
      emphasis on both the generation of fundamental knowledge and product development.
      To achieve this research mission, a highly-trained workforce is required and
      flexible operational methods are needed. In addition, working with certain
      pathogens requires compliance with regulations such as the Centers for Disease
      Control (CDC) and the U.S. Department of Agriculture (USDA) Select Agent
      regulations, which adds to the operational burden. The vast experience from the
      existing studies at Plum Island Animal Disease Center, other U.S. laboratories,
      and those in Europe and Australia with biosafety level 4 (BSL-4) facilities
      designed for large animals, clearly demonstrates the valuable contribution this
      capability brings to the efforts to detect, prepare, prevent and respond to
      livestock and potential zoonotic threats. To raise awareness of these challenges,
      which include biosafety and biosecurity issues, we held a workshop at the 2018
      American Society for Microbiology (ASM) Biothreats conference to further discuss
      the topic with invited experts and audience participants. The workshop covered
      the subjects of research funding and metrics, economic sustainment of drug and
      vaccine development pipelines, workforce turnover, and the challenges of
      maintaining operational readiness of high containment laboratories.

PMID- 30274452
TI  - Potential Animal Reservoir of Mycobacterium ulcerans: A Systematic Review.
AB  - Mycobacterium ulcerans is the causative agent of Buruli ulcer, also known in
      Australia as Daintree ulcer or Bairnsdale ulcer. This destructive skin disease is
      characterized by extensive and painless necrosis of the skin and soft tissue with
      the formation of large ulcers, commonly on the leg or arm. To date, 33 countries
      with tropical, subtropical and temperate climates in Africa, the Americas, Asia
      and the Western Pacific have reported cases of Buruli ulcer. The disease is
      rarely fatal, although it may lead to permanent disability and/or disfigurement
      if not treated appropriately or in time. It is the third most common
      mycobacterial infection in the world after tuberculosis and leprosy. The precise
      mode of transmission of M. ulcerans is yet to be elucidated. Nevertheless, it is
      possible that the mode of transmission varies with different geographical areas
      and epidemiological settings. The knowledge about the possible routes of
      transmission and potential animal reservoirs of M. ulcerans is poorly understood
      and still remains patchy. Infectious diseases arise from the interaction of
      agent, host and environment. The majority of emerging or remerging infectious
      disease in human populations is spread by animals: either wildlife, livestock or
      pets. Animals may act as hosts or reservoirs and subsequently spread the organism
      to the environment or directly to the human population. The reservoirs may or may
      not be the direct source of infection for the hosts; however, they play a major
      role in maintenance of the organism in the environment, and in the mode of
      transmission. This remains valid for M. ulcerans. Possums have been suggested as
      one of the reservoir of M. ulcerans in south-eastern Australia, where possums
      ingest M. ulcerans from the environment, amplify them and shed the organism
      through their faeces. We conducted a systematic review with selected key words on
      PubMed and INFORMIT databases to aggregate available published data on animal
      reservoirs of M. ulcerans around the world. After certain inclusion and exclusion
      criteria were implemented, a total of 17 studies was included in the review. A
      variety of animals around the world e.g., rodents, shrews, possums (ringtail and
      brushtail), horses, dogs, alpacas, koalas and Indian flap-shelled turtles have
      been recorded as being infected with M. ulcerans. The majority of studies
      included in this review identified animal reservoirs as predisposing to the
      emergence and reemergence of M. ulcerans infection. Taken together, from the
      selected studies in this systematic review, it is clear that exotic wildlife and
      native mammals play a significant role as reservoirs for M. ulcerans.

PMID- 30274453
TI  - Mapping Disease Transmission Risk of Nipah Virus in South and Southeast Asia.
AB  - Since 1998, Nipah virus (NiV) (genus: Henipavirus; family: Paramyxoviridae), an
      often-fatal and highly virulent zoonotic pathogen, has caused sporadic outbreak
      events. Fruit bats from the genus Pteropus are the wildlife reservoirs and have a
      broad distribution throughout South and Southeast Asia, and East Africa.
      Understanding the disease biogeography of NiV is critical to comprehending the
      potential geographic distribution of this dangerous zoonosis. This study
      implemented the R packages ENMeval and BIOMOD2 as a means of modeling regional
      disease transmission risk and additionally measured niche similarity between the
      reservoir Pteropus and the ecological characteristics of outbreak localities with
      the Schoener's D index and I statistic. Results indicate a relatively high degree
      of niche overlap between models in geographic and environmental space (D
      statistic, 0.64; and I statistic, 0.89), and a potential geographic distribution
      encompassing 19% (2,963,178 km2) of South and Southeast Asia. This study should
      contribute to current and future efforts to understand the critical ecological
      contributors and geography of NiV. Furthermore, this study can be used as a
      geospatial guide to identify areas of high disease transmission risk and to
      inform national public health surveillance programs.

PMID- 30274454
TI  - The History of Bancroftian Lymphatic Filariasis in Australasia and Oceania: Is
      There a Threat of Re-Occurrence in Mainland Australia?
AB  - Lymphatic filariasis (LF) infects an estimated 120 million people worldwide, with
      a further 856 million considered at risk of infection and requiring preventative
      chemotherapy. The majority of LF infections are caused by Wuchereria bancrofti,
      named in honour of the Australian physician Joseph Bancroft, with the remainder
      due to Brugia malayi and B. timori. Infection with LF through the bite of an
      infected mosquito, can lead to the development of the condition known as
      elephantiasis, where swelling due to oedema leads to loss of function in the
      affected area and thickening of the skin, 'like an elephant'. LF has previously
      been endemic in Australia, although currently, no autochthonous cases occur
      there. Human immigration to Australia from LF-endemic countries, including those
      close to Australia, and the presence of susceptible mosquitoes that can act as
      suitable vectors, heighten the possibility of the reintroduction of LF into this
      country. In this review, we examine the history of LF in Australia and Oceania
      and weigh up the potential risk of its re-occurrence on mainland Australia.

PMID- 30274455
TI  - Scabies in Resource-Poor Communities in Nasarawa State, Nigeria: Epidemiology,
      Clinical Features and Factors Associated with Infestation.
AB  - Epidemiology and clinical features of scabies remain largely unknown in Nigeria's
      rural communities. To fill this gap, we performed a cross-sectional study in
      three rural communities in north central Nigeria. A total of 500 individuals were
      included and examined for scabies infestation; a questionnaire was applied to
      collect socio-demographic and behavioral data. Scabies was diagnosed in 325
      (65.0%) participants. Excoriations (68.6%), vesicles (61.8%), and papules (58.8%)
      were common skin lesions. Itching was the most common symptom (77.5%); 64%
      complained of sleep disturbances. Lymphadenopathy was identified in 48.3%.
      Lesions were most commonly encountered on the abdomen (35.5%), inguinal area
      (19.1%), and interdigital spaces (14.2%). Poverty-related variables, such as
      illiteracy (OR: 7.15; 95% CI: 3.71-13.95), low household income (7.25; 1.19
      88.59), absence of a solid floor inside house (12.17; 2.83-52.34), and
      overcrowding (1.98; 1.08-2.81) were significantly associated with infestation.
      Individual behavior, such as sharing of beds/pillows (2.11; 1.42-3.14) and
      sharing of clothes (2.51; 1.57-3.99), was also highly significantly associated
      with scabies. Regular bathing habits (0.37; 0.24-0.56) and regular use of bathing
      soap (0.36; 0.21-0.53) were protective factors. Scabies is extremely common in
      the communities under study and is associated with considerable morbidity. The
      disease is intrinsically linked with extreme poverty.

PMID- 30274456
TI  - Melioidosis in South America.
AB  - Melioidosis is an emerging disease in the Americas. This paper reviews confirmed
      cases, the presence of Burkholderia pseudomallei and the organization of national
      surveillance policies for melioidosis in South America. Confirmed cases in humans
      have been reported from Ecuador, Venezuela, Colombia, Brazil, and Peru. The
      bacterium has been isolated from the environment in Brazil and Peru. The state of
      Ceara, northeastern region of Brazil, is the only place where specific public
      strategies and policies for melioidosis have been developed. We also discuss the
      urgent need for health authorities in South America to pay greater attention to
      this disease, which has the potential to have a high impact on public health, and
      the importance of developing coordinated strategies amongst countries in this
      region.

PMID- 30274457
TI  - Argument for Inclusion of Strongyloidiasis in the Australian National Notifiable
      Disease List.
AB  - Strongyloidiasis is an infection caused by the helminth, Strongyloides
      stercoralis. Up to 370 million people are infected with the parasite globally,
      and it has remained endemic in the Indigenous Australian population for many
      decades. Strongyloidiasis has been also reported in other Australian populations.
      Ignorance of this disease has caused unnecessary costs to the government health
      system, and been detrimental to the Australian people's health. This manuscript
      addresses the 12 criteria required for a disease to be included in the Australian
      National Notifiable Disease List (NNDL) under the National Health Security Act
      2007 (Commonwealth). There are six main arguments that provide compelling
      justification for strongyloidiasis to be made nationally notifiable and added to
      the Australian NNDL. These are: The disease is important to Indigenous health,
      and closing the health inequity gap between Indigenous and non-Indigenous
      Australians is a priority; a public health response is required to detect cases
      of strongyloidiasis and to establish the true incidence and prevalence of the
      disease; there is no alternative national surveillance system to gather data on
      the disease; there are preventive measures with high efficacy and low side
      effects; data collection is feasible as cases are definable by microscopy, PCR,
      or serological diagnostics; and achievement of the Sustainable Development Goal
      (SDG) # 6 on clean water and sanitation.

PMID- 30274460
TI  - Paediatric Strongyloidiasis in Central Australia.
AB  - Few published studies are available describing the prevalence of paediatric
      strongyloidiasis in endemic areas within Australia. This literature review and
      exploratory clinical audit presents the first seroprevalence data for paediatric
      patients in Central Australia. A total of 16.1% (30/186) of paediatric inpatients
      tested for Strongyloides stercoralis in 2016 were seropositive (95% CI: 11.5% to
      22.1%). Eosinophilia of unknown aetiology was the most common indication for
      testing (91.9%). Seropositive patients were significantly more likely to reside
      in communities outside of Alice Springs (p = 0.02). Seropositive patients were
      noted to have higher mean eosinophil counts with a mean difference of 0.86 *
      108/L (95% CI: 0.56 to 1.16, p < 0.0001), although the limited utility of
      eosinophilia as a surrogate marker of strongyloidiasis has been described
      previously. All seropositive patients were Indigenous. There was no significant
      difference in ages between groups. There was a male predominance in the
      seropositive group, although this was not significant (p = 0.12). Twelve patients
      had known human T-lymphotropic virus 1 (HTLV-1) status and all were seronegative.
      Further research describing the epidemiology of strongyloidiasis in Central
      Australia is required.

PMID- 30274459
TI  - Outer Membrane Protein A Conservation among Orientia tsutsugamushi Isolates
      Suggests Its Potential as a Protective Antigen and Diagnostic Target.
AB  - Scrub typhus threatens one billion people in the Asia-Pacific area and cases have
      emerged outside this region. It is caused by infection with any of the multitude
      of strains of the bacterium Orientia tsutsugamushi. A vaccine that affords
      heterologous protection and a commercially-available molecular diagnostic assay
      are lacking. Herein, we determined that the nucleotide and translated amino acid
      sequences of outer membrane protein A (OmpA) are highly conserved among 51 O.
      tsutsugamushi isolates. Molecular modeling revealed the predicted tertiary
      structure of O. tsutsugamushi OmpA to be very similar to that of the
      phylogenetically-related pathogen, Anaplasma phagocytophilum, including the
      location of a helix that contains residues functionally essential for A.
      phagocytophilum infection. PCR primers were developed that amplified ompA DNA
      from all O. tsutsugamushi strains, but not from negative control bacteria. Using
      these primers in quantitative PCR enabled sensitive detection and quantitation of
      O. tsutsugamushi ompA DNA from organs and blood of mice that had been
      experimentally infected with the Karp or Gilliam strains. The high degree of OmpA
      conservation among O. tsutsugamushi strains evidences its potential to serve as a
      molecular diagnostic target and justifies its consideration as a candidate for
      developing a broadly-protective scrub typhus vaccine.

PMID- 30274458
TI  - Melioidosis in Africa: Time to Uncover the True Disease Load.
AB  - Melioidosis is an often fatal infectious disease with a protean clinical
      spectrum, caused by the environmental bacterial pathogen Burkholderia
      pseudomallei. Although the disease has been reported from some African countries
      in the past, the present epidemiology of melioidosis in Africa is almost entirely
      unknown. Therefore, the common view that melioidosis is rare in Africa is not
      evidence-based. A recent study concludes that large parts of Africa are
      environmentally suitable for B. pseudomallei. Twenty-four African countries and
      three countries in the Middle East were predicted to be endemic, but no cases of
      melioidosis have been reported yet. In this study, we summarize the present
      fragmentary knowledge on human and animal melioidosis and environmental B.
      pseudomallei in Africa and the Middle East. We propose that systematic
      serological studies in man and animals together with environmental investigations
      on potential B. pseudomallei habitats are needed to identify risk areas for
      melioidosis. This information can subsequently be used to target raising clinical
      awareness and the implementation of simple laboratory algorithms for the
      isolation of B. pseudomallei from clinical specimens. B. pseudomallei was most
      likely transferred from Asia to the Americas via Africa, which is shown by
      phylogenetic analyses. More data on the virulence and genomic characteristics of
      African B. pseudomallei isolates will contribute to a better understanding of the
      global evolution of the pathogen and will also help to assess potential
      differences in disease prevalence and outcome.

PMID- 30274462
TI  - Translational Venomics: Third-Generation Antivenomics of Anti-Siamese Russell's
      Viper, Daboia siamensis, Antivenom Manufactured in Taiwan CDC's Vaccine Center.
AB  - The venom proteome of Siamese Russell's viper from Taiwan, alongside
      complementary in vivo lethality neutralization assay and in vitro third
      generation antivenomics assessment of the preclinical efficacy of the homologous
      antivenom manufactured in Taiwan CDC's Vaccine Center, are here reported.
      Taiwanese Russell's viper venom proteome comprised 25 distinct gene products,
      with the heterodimeric PLA2 viperotoxin-F representing the most abundant toxin
      (47.5% of total venom proteome). Coagulation FV-activating serine proteinase (RVV
      V, 14%), the PIV-SVMP activator of FX (RVV-FX, 8.5%), and less abundant toxins
      from nine protein families, make up its venom proteome. Venom composition
      pathology correlations of D. siamensis envenomings in Taiwan are discussed. The
      lethal effect of Taiwanese D. siamensis venom was 0.47 mg/g mouse. Antivenomics
      guided assessment of the toxin recognition landscape of the Taiwanese Russell's
      viper antivenom, in conjunction with complementary in vivo neutralization
      analysis, informed the antivenom's maximal toxin immunorecognition ability (14 mg
      total venom proteins/vial), neutralization capacity (6.5 mg venom/vial), and
      relative content of lethality neutralizing antibodies (46.5% of the toxin-binding
      F(ab')2 antibodies). The antivenomics analysis also revealed suboptimal aspects
      of the CDC-Taiwan antivenom. Strategies to improve them are suggested.

PMID- 30274461
TI  - An Overview of Brucellosis in Cattle and Humans, and its Serological and
      Molecular Diagnosis in Control Strategies.
AB  - Brucellosis is one of the most common contagious and communicable zoonotic
      diseases with high rates of morbidity and lifetime sterility. There has been a
      momentous increase over the recent years in intra/interspecific infection rates,
      due to poor management and limited resources, especially in developing countries.
      Abortion in the last trimester is a predominant sign, followed by reduced milk
      yield and high temperature in cattle, while in humans it is characterized by
      undulant fever, general malaise, and arthritis. While the clinical picture of
      brucellosis in humans and cattle is not clear and often misleading with the
      classical serological diagnosis, efforts have been made to overcome the
      limitations of current serological assays through the development of PCR-based
      diagnosis. Due to its complex nature, brucellosis remains a serious threat to
      public health and livestock in developing countries. In this review, we
      summarized the recent literature, significant advancements, and challenges in the
      treatment and vaccination against brucellosis, with a special focus on developing
      countries.

PMID- 30274463
TI  - The Importance of Water Typologies in Lay Entomologies of Aedes aegypti Habitat,
      Breeding and Dengue Risk: A Study from Northern Australia.
AB  - Dengue fever is making a significant comeback globally and its control still
      depends largely on residents' actions. Community awareness and education are
      central to its management; however, programmes have had limited impact, because
      they are often based on short-term research and limited awareness of the socio
      ecological contexts wherein local knowledge of dengue and its vectors (lay
      entomology) is produced and enacted in and through place. Long-term studies of
      lay knowledge of dengue vectors are very rare, even though they are essential to
      the development of effective, targeted community education campaigns and
      mobilisation. In this paper, we examine the popular belief that dengue vector,
      Aedes aegypti, is ubiquitous in the north Australian landscape and demonstrate
      how local typologies of water are central to the reasoning underwriting this
      assumption. We show how these logics are fortified by people's lived experiences
      of mosquitoes and the watery abodes they are thought to reside in, as well as
      through key messages from health education. We posit that long term, context
      sensitive research approaches are better able to identify, understand and later
      address and challenge assumptions and may be more effective at informing,
      empowering and mobilizing the public to combat dengue fever.

PMID- 30274464
TI  - Schistosome Vaccines for Domestic Animals.
AB  - Schistosomiasis is recognized as a tropical disease of considerable public health
      importance, but domestic livestock infections due to Schistosoma japonicum, S.
      bovis, S. mattheei and S. curassoni are often overlooked causes of significant
      animal morbidity and mortality in Asia and Africa. In addition, whereas
      schistosomiasis japonica is recognized as an important zoonosis in China and the
      Philippines, reports of viable schistosome hybrids between animal livestock
      species and S. haematobium point to an underappreciated zoonotic component of
      transmission in Africa as well. Anti-schistosome vaccines for animal use have
      long been advocated as part of the solution to schistosomiasis control,
      benefitting humans and animals and improving the local economy, features aligning
      with the One Health concept synergizing human and animal health. We review the
      history of animal vaccines for schistosomiasis from the early days of irradiated
      larvae and then consider the recombinant DNA technology revolution and its impact
      in developing schistosome vaccines that followed. We evaluate the major
      candidates tested in livestock, including the glutathione S-transferases,
      paramyosin and triose-phosphate isomerase, and summarize some of the future
      challenges that need to be overcome to design and deliver effective anti
      schistosome vaccines that will complement current control options to achieve and
      sustain future elimination goals.

PMID- 30274466
TI  - Neglected and Emerging Tropical Diseases in South and Southeast Asia and Northern
      Australia.

PMID- 30274465
TI  - A Rapid Appraisal of Factors Influencing Praziquantel Treatment Compliance in Two
      Communities Endemic for Schistosomiasis in Cote d'Ivoire.
AB  - Over the past decade, a significant reduction in the prevalence of
      schistosomiasis has been achieved, partially explained by the large-scale
      administration of praziquantel. Yet, the burden of schistosomiasis remains
      considerable, and factors influencing intervention coverage are important. This
      study aimed to deepen the understanding of low treatment coverage rates observed
      in two schistosomiasis-endemic villages in Cote d'Ivoire. The research was
      conducted in August 2015, in Moronou and Bigouin, two villages of Cote d'Ivoire
      that are endemic for Schistosoma haematobium and S. mansoni, respectively. After
      completion of a clinical trial, standard praziquantel treatment (single 40 mg/kg
      oral dose) was offered to all village inhabitants by community health workers
      using a house-to-house approach. Factors influencing treatment coverage were
      determined by a questionnaire survey, randomly selecting 405 individuals. The
      overall treatment coverage rate was only 47.6% (2730/5733) with considerable
      intervillage heterogeneity (27.7% in Bigouin (302/1091) versus 52.3% in Moronou
      (2428/4642)). Among the 200 individuals interviewed in Moronou, 50.0% were
      administered praziquantel, while only 19.5% of the 205 individuals interviewed in
      Bigouin received praziquantel. The main reasons for low treatment coverage were
      work-related (agricultural activities), the bitter taste of praziquantel and
      previous experiences with adverse events. The most suitable period for treatment
      campaigns was reported to be the dry season. More than three-quarter of the
      interviewees who had taken praziquantel (overall, 116/140; Moronou, 84/100;
      Bigouin, 32/40) declared that they would not participate in future treatments (p
      < 0.001). In order to enhance praziquantel treatment coverage, careful
      consideration should be given to attitudes and practices, such as prior or
      perceived adverse events and taste of praziquantel, and appropriate timing,
      harmonized with agricultural activities. Without such understanding, breaking the
      transmission of schistosomiasis remains a distant goal.

PMID- 30274467
TI  - From Incriminating Stegomyia fasciata to Releasing Wolbachia pipientis:
      Australian Research on the Dengue Virus Vector, Aedes aegypti, and Development of
      Novel Strategies for Its Surveillance and Control.
AB  - Globally, the dengue viruses (DENVs) infect approximately 300 million people
      annually. Australia has a history of epidemic dengue, with outbreaks in the early
      decades of the twentieth century responsible for tens of thousands of cases.
      Seminal experiments conducted by Australian scientists during these outbreaks
      were the first to incriminate Aedes aegypti as a major vector of dengue viruses.
      One hundred years later, Australian scientists are playing a lead role in the
      development of surveillance and suppression strategies that target this mosquito
      species. Surveillance of Ae. aegypti populations and their associated dengue risk
      was greatly improved by understanding the contribution of key premises, key
      containers, and cryptic larval habitats to mosquito productivity, and, more
      recently, the development of novel adult traps. In terms of mosquito control,
      targeted indoor residual pyrethroid spraying and community-based biological
      control utilizing predatory copepods can significantly reduce Ae. aegypti
      populations. The release of Ae. aegypti transinfected with the virus-blocking
      bacterium, Wolbachia, provides a promising strategy for limiting DENV
      transmission. These diverse strategies developed by Australian scientists have
      the potential to alleviate the burden of dengue in the future, whether it is at
      the local level or as part of a country-wide program.

PMID- 30274468
TI  - Coverage, Timelines, and Determinants of Incomplete Immunization in Bangladesh.
AB  - : Immunization has become one of the major contributors to public health globally
      as it prevents communicable disease, particularly in children. The objective of
      this study was to estimate the extent of timely immunization coverage and to
      investigate the determinants of incomplete and untimely vaccination. METHODS: The
      study used data from the latest Bangladesh Demographic Health Survey (BDHS) 2014.
      A total sample of 1631 children aged 12-23 months who had an Expanded Program on
      Immunization (EPI) card and immunization history were analyzed. Multivariable
      logistic regression models were used to determine the significant influencing
      factors on untimely vaccination (BCG, pentavalent vaccine/OPV, and measles) and
      incomplete vaccination. The results were presented in terms of adjusted odds
      ratio (AOR) with a 95% confidence interval and a significance level p < 0.05.
      RESULTS: The proportions of children who received timely vaccinations were 24%
      for BCG, 46% for pentavalent 3, and 53% for measles, whereas 76%, 51%, and 36%
      children failed to receive the BCG, pentavalent 3, and measles vaccines,
      respectively, in a timely manner. The proportion of early vaccination was 3% for
      pentavalent 3 and 12% for measles. Several significant influencing factors
      including age, maternal education and working status, awareness of community
      clinics, socioeconomic status, and geographic variation significantly contributed
      to untimely and incomplete vaccination of children in Bangladesh. CONCLUSIONS:
      The study identified some key determinants of untimely and incomplete childhood
      vaccinations in the context of Bangladesh. The findings will contribute to the
      improvement of age-specific vaccination and support policy makers in taking the
      necessary control strategies with respect to delayed and early vaccination in
      Bangladesh.

PMID- 30274470
TI  - Serological Cross-Reactivity among Orientia tsutsugamushi Serotypes but Not with
      Rickettsia japonica in Japan.
AB  - The rickettsial diseases Japanese spotted fever (JSF) and scrub typhus (ST) are
      caused by Rickettsia japonica and Orientia tsutsugamushi, respectively. The
      diseases share clinical symptoms, such as fever, rash, and eschar. However, there
      are no systematical investigations of the serological cross-reactivity between R.
      japonica and O. tsutsugamushi. Also, the serological cross-reactivity among O.
      tsutsugamushi serotypes is still unclear. We analyzed 1406 cases tested by
      indirect immunoperoxidase assay using seven rickettsial antigens-one R. japonica
      and six O. tsutsugamushi serotypes-between 2003 and 2016 at two reference centers
      in Japan. Of these, 167 JSF and 190 ST cases were serologically diagnosed. None
      of the ST cases had a significant increase in IgM titers against R. japonica. Six
      JSF cases showed IgG titers of >=40 against O. tsutsugamushi, but no IgG titer
      showed a significant elevation in the convalescent phase sample. We observed a
      substantial degree of cross-reactivity between O. tsutsugamushi serotypes. Cross
      reactivity was significant among Karp, Hirano/Kuroki, and Kato types and between
      Gilliam and Irie/Kawasaki types in IgM, while the Shimokoshi type was less cross
      reactive than the others. In conclusion, there is no serological cross-reaction
      between R. japonica and O. tsutsugamushi. The cross-reactivity among
      O.tsutsugamushi varies depending on serotypes.

PMID- 30274469
TI  - A 12-Year Retrospective Study of Invasive Amoebiasis in Western Sydney: Evidence
      of Local Acquisition.
AB  - In Australia, amoebiasis is thought to occur in travellers, immigrants from
      endemic areas, and among men who have sex with men. Prevalence of amoebiasis in
      communities with immigrants from Entamoeba histolytica-endemic countries is
      unknown. The present study is a retrospective case series analysis of patients
      with laboratory-confirmed amoebiasis from Western Sydney Local Health District,
      Australia, between years 2005 and 2016. Forty-nine patients with amoebiasis were
      identified, resulting in an estimated annual incidence of up to 1.1 cases per
      100,000 adults. Many were born in Australia (15/47) and India (12/47). Three
      patients (3/37) had no history of overseas travel, two others had not travelled
      to an endemic country, and an additional two had a very remote history of
      overseas travel; one died of fulminant amoebic colitis. Three patients (3/16)
      were employed in the food industry and one had a history of colonic irrigation in
      an Australian 'wellness clinic'. Patients had invasive amoebiasis with either
      liver abscess (41/48) or colitis (7/48), diagnosed most commonly by serology.
      Invasive procedures were common, including aspiration of liver abscess (28/41),
      colonoscopy (11/49), and partial hepatectomy (1/49). Although rare, local
      acquisition of amoebiasis occurs in Western Sydney and contributes to significant
      morbidity and hospital admissions.

PMID- 30274471
TI  - On the Home Front: Specialised Reference Testing for Dengue in the Australasian
      Region.
AB  - Reference laboratories are vital for disease control and interpreting the
      complexities and impact of emerging pathogens. The role of these centralized
      facilities extends beyond routine screening capabilities to provide rapid,
      specific, and accurate diagnoses, advanced data analysis, consultation services,
      and sophisticated disease surveillance and monitoring. Within the Australasian
      region, the Public Health Virology Laboratory (PHV), Forensic and Scientific
      Services, Department of Health, Queensland Government, Australia, and the
      Institute of Environmental Science and Research Limited (ESR), New Zealand (NZ)
      perform specialised reference testing and surveillance for dengue viruses (DENVs)
      and other emerging arthropod-borne viruses (arboviruses), including chikungunya
      virus (CHIKV) and Zika virus (ZIKV). With a focus on DENV, we review the
      reference testing performed by PHV (2005 to 2017) and ESR (2008 to 2017). We also
      describe how the evolution and expansion of reference-based methodologies and the
      adoption of new technologies have provided the critical elements of preparedness
      and early detection that complement frontline public health control efforts and
      limit the spread of arboviruses within Australasia.

PMID- 30274473
TI  - Day Biting Habits of Mosquitoes Associated with Mangrove Forests in Kedah,
      Malaysia.
AB  - Due to conservation and rehabilitation efforts, mangrove forests represent some
      of the largest environmental niches in Malaysia. However, there is little
      information on the potential risks posed by mosquitoes that are directly and
      indirectly associated with mangrove forests. To study the potential health risk
      to humans active within and in close vicinity of mangrove forests, this research
      focused on the day biting habits of mosquitoes in mangrove forests of Kedah,
      Malaysia. The bare leg catch (BLC) method was used to collect adult mosquitoes
      during a 12-h period from 7:30 a.m. to 7:30 p.m. in both disturbed and less
      disturbed areas of mangroves. In total, 795 adult mosquitoes from 5 genera and 8
      species were collected, and over 65% of the total mosquitoes were collected from
      the less disturbed area. The predominant species from the less disturbed area was
      Verrallina butleri; in the disturbed area the dominant species was Culex sitiens.
      The peak biting hour differed for each species, with Aedes albopictus and Cx.
      sitiens recorded as having a bimodal biting activity peak during dawn and dusk.
      For Ve. butleri an erratic pattern of biting activity was recorded in the less
      disturbed area but it peaked during the early daytime for both collection points.
      Overall, the distinct pattern of day biting habits of mosquitoes within mangroves
      peaked during dawn and dusk for the less disturbed area but was irregular for the
      disturbed area throughout the day. The presence of vectors of pathogens such as
      Ae. albopictus for both areas raises the need for authorities to consider
      management of mosquitoes in mangrove forests.

PMID- 30274472
TI  - Exotic Parasite Threats to Australia's Biosecurity-Trade, Health, and
      Conservation.
AB  - Parasites have threatened Australia's biosecurity since the early days of
      European settlement. Tick fever in cattle and liver fluke, along with their
      invertebrate hosts, and hydatid disease head the list of parasites that are still
      impacting livestock industries. In addition, there are many parasites that have
      been introduced that are of significance to public health as well as the
      conservation of native wildlife. As a consequence of these early arrivals,
      Australia has become much more aware of its vulnerability should parasites such
      as Trichinella and Trypanosoma evansi become established in Australia. However,
      recent discoveries concerning Leishmania and other trypanosomes have demonstrated
      that Australia must not become complacent and reliant on dogma when considering
      the potential emergence of new threats to its biosecurity. In this short review,
      the major parasite threats to Australia's biosecurity are summarised, some
      misconceptions are emphasised, and attention is given to the importance of
      challenging dogma in the face of a dearth of information about Australian native
      fauna.

PMID- 30274475
TI  - Epidemiology and Spatiotemporal Patterns of Leprosy Detection in the State of
      Bahia, Brazilian Northeast Region, 2001-2014.
AB  - The detection of leprosy cases is distributed unequally in Brazil, with high-risk
      clusters mainly in the North and Northeast regions. Knowledge on epidemiology and
      spatiotemporal patterns of leprosy occurrence and late diagnosis in these areas
      is critical to improve control measures. We performed a study including all
      leprosy cases notified in the 417 municipalities of Bahia state, from 2001 to
      2014. New case detection (overall and pediatric <15 years) and grade 2 disability
      (G2D) rates were calculated and stratified according to socio-demographic
      variables. Spatial analyses were performed to detect high-risk areas for
      occurrence and late diagnosis. A total of 40,060 new leprosy cases was reported
      in the period (mean = 2861 cases/year), 3296 (8.2%) in <15-year-olds, and 1921
      (4.8%) with G2D. The new case detection rate was 20.41 cases/100,000 inhabitants
      (95% CI: 19.68-21.17). A higher risk was identified in older age groups (RR =
      8.45, 95% CI: 7.08-10.09) and in residents living in the state capital (RR =
      5.30, 95% CI: 4.13-6.79), in medium-sized cities (RR = 2.80; 95% CI: 2.50-3.13),
      and in the west (RR = 6.56, 95% CI: 5.13-8.39) and far south regions of the state
      (RR = 6.56, 95% CI: 5.13-8.39). A higher risk of G2D was associated with male
      gender (RR = 2.43, 95% CI: 2.20-2.67), older age (RR = 44.08, 95% CI: 33.21
      58.51), Afro-Brazilian ethnicity (RR = 1.59; 95% CI: 1.37-1.85), living in medium
      sized cities (RR = 2.60; 95% CI: 2.27-2.96) and residency in the north (RR =
      5.02; 95% CI: 3.74-6.73) and far south (RR = 7.46; 95% CI: 5.58-9.98) regions.
      Heterogeneous space-time patterns of leprosy distribution were identified,
      indicating high endemicity, recent transmission, and late diagnosis. This
      heterogeneous distribution of the disease was observed throughout the study
      period. Leprosy remains a relevant public health problem in Bahia state. The
      disease has a focal distribution. We reinforce the importance of integrating
      surveillance, prevention and control actions in regions of higher risk of leprosy
      detection and late diagnosis, and in the most vulnerable populations.

PMID- 30274474
TI  - Differential Susceptibility of Male Versus Female Laboratory Mice to Anaplasma
      phagocytophilum Infection.
AB  - Human granulocytic anaplasmosis (HGA) is a debilitating, non-specific febrile
      illness caused by the granulocytotropic obligate intracellular bacterium called
      Anaplasma phagocytophilum. Surveillance studies indicate a higher prevalence of
      HGA in male versus female patients. Whether this discrepancy correlates with
      differential susceptibility of males and females to A. phagocytophilum infection
      is unknown. Laboratory mice have long been used to study granulocytic
      anaplasmosis. Yet, sex as a biological variable (SABV) in this model has not been
      evaluated. In this paper, groups of male and female C57Bl/6 mice that had been
      infected with A. phagocytophilum were assessed for the bacterial DNA load in the
      peripheral blood, the percentage of neutrophils harboring bacterial inclusions
      called morulae, and splenomegaly. Infected male mice exhibited as much as a 1.85
      fold increase in the number of infected neutrophils, which is up to a 1.88-fold
      increase in the A. phagocytophilum DNA load, and a significant increase in spleen
      size when compared to infected female mice. The propensity of male mice to
      develop a higher level of A. phagocytophilum infection is relevant for studies
      utilizing the mouse model. This stresses the importance of including SABV and
      aligns with the observed higher incidence of infection in male versus female
      patients.

PMID- 30274476
TI  - New Immuno-Epidemiological Biomarker of Human Exposure to Aedes Vector Bites:
      From Concept to Applications.
AB  - Arthropod-borne viruses (arboviruses) such as dengue virus (DENV), chikungunya
      virus (CHIKV), Zika virus (ZIKV), and yellow fever virus (YFV) are the most
      important 'emerging pathogens' because of their geographic spread and their
      increasing impact on vulnerable human populations. To fight against these
      arboviruses, vector control strategies (VCS) remain one of the most valuable
      means. However, their implementation and monitoring are labour intensive and
      difficult to sustain on large scales, especially when transmission and Aedes
      mosquito densities are low. To increase the efficacy of VCS, current
      entomological methods should be improved by new complementary tools which measure
      the risk of arthropod-borne diseases' transmission. The study of human-Aedes
      immunological relationships can provide new promising serological tools, namely
      antibody-based biomarkers, allowing to accurately estimate the human-Aedes
      contact and consequently, the risk of transmission of arboviruses and the
      effectiveness of VCS. This review focuses on studies highlighting the concept,
      techniques, and methods used to develop and validate specific candidate
      biomarkers of human exposure to Aedes bites. Potential applications of such
      antibody-based biomarkers of exposure to Aedes vector bites in the field of
      operational research are also discussed.

PMID- 30274478
TI  - Cushing Syndrome due to Inappropriate Corticosteroid Topical Treatment of
      Undiagnosed Scabies.
AB  - The uncontrolled sale of topical corticosteroids has become an important risk
      factor for the development of iatrogenic Cushing syndrome in children, especially
      in countries where medications are sold over the counter. This is exacerbated by
      the lack of information for both the patients and pharmacists. This report
      documents a series of eight cases of iatrogenic Cushing syndrome secondary to an
      inappropriate use of topical steroids, due to a misdiagnosis of scabies.

PMID- 30274479
TI  - Risk Mapping of Visceral Leishmaniasis: A Spatial Regression Model for Attica
      Region, Greece.
AB  - Visceral Leishmaniasis (VL) is endemic to the Attica region of Greece. The
      geographical distribution of VL cases was analyzed employing methods of spatial
      analysis in a GIS environment. A geographic database was constructed including
      data for the disease cases and environmental factors, such as land cover types,
      stray dog population, and socioeconomic factors. Classic and spatial regression
      models are presented that suggest the factors contributing most to the incidence
      of leishmaniasis are green urban areas and the population of stray dogs in the
      municipalities of Attica region. The results of the spatial regression model were
      more accurate, thus were used to produce a disease risk map. This map indicates
      the high-risk municipalities in which surveillance for the control of
      leishmaniasis is necessary.

PMID- 30274477
TI  - DNA Diagnostics for Schistosomiasis Control.
AB  - Despite extensive efforts over the last few decades, the global disease burden of
      schistosomiasis still remains unacceptably high. This could partly be attributed
      to the lack of accurate diagnostic tools for detecting human and animal
      schistosome infections in endemic areas. In low transmission and low prevalence
      areas where schistosomiasis elimination is targeted, case detection requires a
      test that is highly sensitive. Diagnostic tests with low sensitivity will miss
      individuals with low infection intensity and these will continue to contribute to
      transmission, thereby interfering with the efficacy of the control measures
      operating. Of the many diagnostic approaches undertaken to date, the detection of
      schistosome DNA using DNA amplification techniques including polymerase chain
      reaction (PCR) provide valuable adjuncts to more conventional microscopic and
      serological methods, due their accuracy, high sensitivity, and the capacity to
      detect early pre-patent infections. Furthermore, DNA-based methods represent
      important screening tools, particularly in those endemic areas with ongoing
      control where infection prevalence and intensity have been reduced to very low
      levels. Here we review the role of DNA diagnostics in the path towards the
      control and elimination of schistosomiasis.

PMID- 30274480
TI  - Long-Range Diagnosis of and Support for Skin Conditions in Field Settings.
AB  - Skin diseases are a significant cause of morbidity and mortality worldwide;
      however, access to dermatology services are critically limited, particularly in
      low- to middle-income countries (LMIC), where there is an overall shortage of
      physicians. Implementation of long-range technological support tools has been
      growing in an effort to provide quality dermatology care to even the most remote
      settings globally. eHealth strategies can provide realistic healthcare solutions
      if implemented in a feasible and sensitive way, customizing tools to address the
      unique needs and resource limitations of the local setting. This article
      summarizes the various types of telemedicine and mobile health (mHealth) tools
      and their practical applications and benefits for patient care. The challenges
      and barriers of teledermatology are discussed, as well as steps to consider when
      implementing a new teledermatology initiative. eHealth arguably offers one of the
      most flexible and realistic tools for providing critically needed access to
      dermatology skills in underserved LMICs.

PMID- 30274481
TI  - When Should the Emphasis on Schistosomiasis Control Move to Elimination?
AB  - The stated goal of the World Health Organization's program on schistosomiasis is
      paraphrased as follows: to control morbidity and eliminate transmission where
      feasible. Switching from a goal of controlling morbidity to interrupting
      transmission may well be currently feasible in some countries in the Caribbean,
      some areas in South America, northern Africa, and selected endemic areas in sub
      Saharan Africa where there have been improvements in sanitation and access to
      clean water. However, in most of sub-Saharan Africa, where programmatic
      interventions still consist solely of annual mass drug administration, such a
      switch in strategies remains premature. There is a continued need for operational
      research on how best to reduce transmission to a point where interruption of
      transmission may be achievable. The level of infection at which it is feasible to
      transition from control to elimination must also be defined. In parallel, there
      is also a need to develop and evaluate approaches for achieving and validating
      elimination. There are currently neither evidence-based methods nor tools for
      breaking transmission or verifying that it has been accomplished. The basis for
      these statements stems from numerous studies that will be reviewed and summarized
      in this article; many, but not all of which were undertaken as part of SCORE, the
      Schistosomiasis Consortium for Operational Research and Evaluation.

PMID- 30274482
TI  - Treading the Path towards Genetic Control of Snail Resistance to Schistosome
      Infection.
AB  - Schistosomiasis remains the most important tropical snail-borne trematodiasis
      that threatens many millions of human lives. In achieving schistosomiasis
      elimination targets, sustainable control of the snail vectors represents a
      logical approach. Nonetheless, the ineffectiveness of the present snail control
      interventions emphasizes the need to develop new complementary strategies to
      ensure more effective control outcomes. Accordingly, the use of genetic
      techniques aimed at driving resistance traits into natural vector populations has
      been put forward as a promising tool for integrated snail control. Leveraging the
      Biomphalaria-Schistosoma model system, studies unraveling the complexities of the
      vector biology and those exploring the molecular basis of snail resistance to
      schistosome infection have been expanding in various breadths, generating many
      significant discoveries, and raising the hope for future breakthroughs. This
      review provides a compendium of relevant findings, and without neglecting the
      current existing gaps and potential future challenges, discusses how a transgenic
      snail approach may be adapted and harnessed to control human schistosomiasis.

PMID- 30274483
TI  - Community Involvement in the Care of Persons Affected by Podoconiosis-A Lesson
      for Other Skin NTDs.
AB  - Podoconiosis is a neglected tropical disease (NTD) characterized by lower-leg
      swelling (lymphedema), which is caused by long-term exposure to irritant red-clay
      soils found within tropical volcanic high-altitude environments with heavy
      rainfall. The condition places a substantial burden on affected people, their
      families and communities, including disability, economic consequences, social
      exclusion, and stigma; mental disorders and distress are also common. This paper
      focuses on community-based care of podoconiosis, and, in particular, the role
      that community involvement can have in the reduction of stigma against people
      affected by podoconiosis. We first draw on research conducted in Ethiopia for
      this, which has included community-based provision of care and treatment,
      education, and awareness-raising, and socioeconomic rehabilitation to reduce
      stigma. Since people affected by podoconiosis and other skin NTDs often suffer
      the double burden of mental-health illness, which is similarly stigmatized, we
      then point to examples from the mental-health field in low-resource community
      settings to suggest avenues for stigma reduction and increased patient engagement
      that may be relevant across a range of skin NTDs, though further research is
      needed on this.

PMID- 30274484
TI  - A Teledermatology Pilot Programme for the Management of Skin Diseases in Primary
      Health Care Centres: Experiences from a Resource-Limited Country (Mali, West
      Africa).
AB  - In sub-Saharan Africa, in particular in rural areas, patients have limited access
      to doctors with specialist skills in skin diseases. To address this issue, a
      teledermatology pilot programme focused on primary health centres was set up in
      Mali. This study was aimed at investigating the feasibility of this programme and
      its impact on the management of skin diseases. The programme was based on the
      store-and-forward model. Health care providers from 10 primary centres were
      trained to manage common skin diseases, to capture images of skin lesions, and to
      use an e-platform to post all cases beyond their expertise for dermatologists in
      order to obtain diagnosis and treatment recommendations. After training, the
      cases of 180 patients were posted by trained health workers on the platform.
      Ninety-six per cent of these patients were properly managed via the responses
      given by dermatologists. The mean time to receive the expert's response was 32 h
      (range: 13 min to 20 days). Analysis of all diseases diagnosed via the platform
      revealed a wide range of skin disorders. Our initiative hugely improved the
      management of all skin diseases in the targeted health centres. In developing
      countries, Internet accessibility and connection quality represent the main
      challenges when conducting teledermatology programmes.

PMID- 30274486
TI  - First Case Report of a Near Lethal Envenomation by a Salomonelaps par (Solomons
      Coral Snake) in the Solomon Islands.
AB  - Venomous snake bites in the Solomon Islands can be very dangerous due to lack of
      access to health care. There are no documented case reports of envenomation by
      snake bites in the Solomon Islands. This case report highlights the management of
      a patient with potentially lethal neurotoxicity secondary to a Solomonelaps par
      (Solomons coral snake) in a low resource setting. This case identifies the
      potential benefit of further research to determine the incidence of lethal
      envenomation as well as analysing the venom to determine if any commercially
      available antivenom would be useful in the treatment of envenomation by
      Salomonelaps par and other venomous snakes. There should be consideration given
      to providing education on first aid for people living in remote areas as well as
      education for health workers.

PMID- 30274485
TI  - Rabies in the Caribbean: A Situational Analysis and Historic Review.
AB  - Rabies virus is the only Lyssavirus species found in the Americas. In discussions
      about rabies, Latin America and the Caribbean are often grouped together. Our
      study aimed to independently analyse the rabies situation in the Caribbean and
      examine changes in rabies spatiotemporal epidemiology. A questionnaire was
      administered to the 33 member countries and territories of the Caribbean Animal
      Health Network (CaribVET) to collect current data, which was collated with a
      literature review. Rabies was endemic in ten Caribbean localities, with the dog,
      mongoose, and vampire bat identified as enzootic reservoirs. The majority of
      animal cases occurred in Puerto Rico, the Dominican Republic, and Haiti, while
      human cases only consistently occurred in the latter two areas. Rabies
      vaccination was conducted for high-risk animal populations with variable
      coverage, and rabies diagnostic capacities varied widely throughout the region.
      Illegal importation and natural migration of animals may facilitate the
      introduction of rabies virus variants into virus-naive areas. Passive
      surveillance, together with enhanced methods and serological screening
      techniques, can therefore be of value. The insularity of the Caribbean makes it
      ideal for conducting pilot studies on reservoir host population management. Best
      practice guidelines developed for these reservoir hosts can be individually
      modified to the epidemiological status and available resources within each
      locality.

PMID- 30274487
TI  - Melioidosis in Hong Kong.
AB  - Melioidosis, although endemic in many parts of Southeast Asia, has not been
      systematically studied in Hong Kong, which is a predominantly urban area located
      in the subtropics. This review describes the early outbreaks of melioidosis in
      captive animals in Hong Kong in the 1970s, as well as the early reports of human
      clinical cases in the 1980s. A review of all hospitalized human cases of culture
      confirmed melioidosis in the last twenty years showed an increasing trend in the
      incidence of the disease, with significant mortality observed. The lack of
      awareness of this disease among local physicians, the delay in laboratory
      diagnosis and the lack of epidemiological surveillance are among the greatest
      challenges of managing melioidosis in the territory.

PMID- 30274488
TI  - Advances in the Treatment of Yaws.
AB  - Yaws is one of the three endemic treponematoses and is recognised by the World
      Health Organization as a neglected tropical disease. Yaws is currently reported
      in 15 countries in the Pacific, South-East Asia, West and Central Africa,
      predominantly affects children, and results in destructive lesions of the skin
      and soft tissues. For most of the twentieth century penicillin-based treatment
      was the standard of care and resistance to penicillin has still not been
      described. Recently, oral azithromycin has been shown to be an effective
      treatment for yaws, facilitating renewed yaws eradication efforts. Resistance to
      azithromycin is an emerging threat and close surveillance will be required as
      yaws eradication efforts are scaled up globally.

PMID- 30274489
TI  - 'Know Your Epidemic': Are Prisons a Potential Barrier to TB Elimination in an
      Australian Context?
AB  - Globally, rates of tuberculosis (TB) cases in prisons are substantially higher
      than in the general population. The goal of this study was to review TB
      notifications in Victorian correctional facilities, and consider whether
      additional interventions towards TB elimination may be useful in this setting.
      All patients who were notified with or treated for TB in the Australian state of
      Victoria from 1 January 2003 to 1 December 2017 were included in this study.
      Descriptive analysis was performed. Demographic and treatment outcome data for
      individuals with and without a history of incarceration were reviewed and
      compared. Of the 5645 TB cases notified during the study period, 26 (0.5%) had a
      history of being incarcerated in correctional facilities while receiving
      treatment for TB. There were 73,238 inmates in Victorian correctional facilities
      over the same study period, meaning that approximately 0.04% of inmates were
      diagnosed or treated with TB disease in correctional facilities. Incarcerated
      individuals were more likely to have positive sputum smears and cavitation
      compared with nonincarcerated people with TB. There was no significant difference
      in treatment outcomes between the general TB population and those who had a
      history of incarceration during their treatment. There is a low apparent rate of
      TB in Victorian prisoners, and prisons do not contribute significantly to TB
      incidence in Victoria. Overall, TB outcomes do not differ between prisoners and
      nonprisoners. Ongoing efforts to sustain these lower rates and comparable
      outcomes in this vulnerable cohort are important for continued progress towards
      TB elimination.

PMID- 30274492
TI  - Acute Poisonings at a Regional Referral Hospital in Western Kenya.
AB  - The emergency department (ED) of the Jaramogi Oginga Odinga Teaching and Referral
      Hospital (JOOTRH) handles many cases of poisoning. However, there is scant
      information on the factors, agents, and outcomes of poisoning at the hospital.
      The aim of this work was to determine the factors, agents, and outcomes of
      poisoning at JOOTRH. Records of patients who presented to JOOTRH with symptoms of
      poisoning between January 2011 and December 2016 were retrieved. Data on age,
      gender, offending agents, time, and season of exposure were collected.
      Information on the route of exposure, motive, and clinical symptoms of poisoning
      was also included. Other information included the laboratory evaluation, first
      aid measures, period of hospitalization, and outcome of poisoning. Mean, standard
      deviation, frequencies and bar graphs were used to describe the demographic
      factors of the study population. Multivariate logistic regression was used to
      determine the strength of association between risk factors and outcome of
      poisoning among patients. The level of significance for inferential analysis was
      set at 5%. There were 385 cases of poisoning: 57.9% (223/385) were male, 31.9%
      (123/385) were 13-24 years of age, and 83.9% (323/385) of exposures were in
      Kisumu County. The peak time of exposure was 6:00-00:00, and 23.6% (91/385)
      presented 1-4 h after exposure. About 62.9% (242/385) of the cases were due to
      accidental poisoning. Snakebites and organophosphates (OPPs) contributed to 33.0%
      (127/385) and 22.1% (85/385) of all cases, respectively. About 62.1% (239/385) of
      exposures were oral, and 63.9% (246/385) of all cases occurred in the rainy
      season. Additionally, 49.2% (60/122) of intentional poisoning was due to family
      disputes, and 16.1% (10/62) of pre-hospital first aid involved the use of
      tourniquets and herbal medicine. About 28.6% (110/385) of the victims were
      subjected to laboratory evaluation and 83.9% (323/385) were hospitalized for
      between 1-5 days. Other results indicated that 80.0% (308/385) responded well to
      therapy, while 7.3% (28/385) died, 68% (19/28) of whom were male. Furthermore,
      39.3% (11/28) of the deaths were related to OPPs. Our findings suggest that the
      earlier the victims of poisoning get to the hospital, the more likely they are to
      survive after treatment is initiated. Similarly, victims of poisoning due to
      parental negligence are more likely to survive after treatment compared to other
      causes of poisoning, including family disputes, love affairs, snakebites, and
      psychiatric disorders. The management of JOOTRH should consider allocating
      resources to support the development of poison management and control.

PMID- 30274490
TI  - Onchodermatitis: Where Are We Now?
AB  - Onchocerciasis causes debilitating pruritus and rashes as well as visual
      impairment and blindness. Prior to control measures, eye disease was particularly
      prominent in savanna areas of sub-Saharan Africa whilst skin disease was more
      common across rainforest regions of tropical Africa. Mass drug distribution with
      ivermectin is changing the global scene of onchocerciasis. There has been
      successful progressive elimination in Central and Southern American countries and
      the World Health Organization has set a target for elimination in Africa of 2025.
      This literature review was conducted to examine progress regarding onchocercal
      skin disease. PubMed searches were performed using keywords 'onchocerciasis',
      'onchodermatitis' and 'onchocercal skin disease' over the past eight years.
      Articles in English, or with an English abstract, were assessed for relevance,
      including any pertinent references within the articles. Recent progress in
      awareness of, understanding and treatment of onchocercal skin disease is reviewed
      with particular emphasis on publications within the past five years. The global
      burden of onchodermatitis is progressively reducing and is no longer seen in
      children in many formerly endemic foci.

PMID- 30274491
TI  - Diagnostic Accuracy of the InBios Scrub Typhus DetectTM ELISA for the Detection
      of IgM Antibodies in Chittagong, Bangladesh.
AB  - Here we estimated the accuracy of the InBios Scrub Typhus DetectTM immunoglobulin
      M (IgM) ELISA to determine the optimal optical density (OD) cut-off values for
      the diagnosis of scrub typhus. Patients with undifferentiated febrile illness
      from Chittagong, Bangladesh, provided samples for reference testing using (i)
      qPCR using the Orientia spp. 47-kDa htra gene, (ii) IFA >=1:3200 on admission,
      (iii) immunofluorescence assay (IFA) >=1:3200 on admission or 4-fold rise to
      >=3200, and (iv) combination of PCR and IFA positivity. For sero-epidemiological
      purposes (ELISA vs. IFA >=1:3200 on admission or 4-fold rise to >=3200), the OD
      cut-off for admission samples was >=1.25, resulting in a sensitivity (Sn) of 91.5
      (95% confidence interval (95% CI: 96.8-82.5) and a specificity (Sp) of 92.4 (95%
      CI: 95.0-89.0), while for convalescent samples the OD cut-off was >=1.50 with Sn
      of 66.0 (95% CI: 78.5-51.7) and Sp of 96.0 (95% CI: 98.3-92.3). Comparisons
      against comparator reference tests (ELISA vs. all tests including PCR) indicated
      the most appropriate cut-off OD to be within the range of 0.75-1.25. For
      admission samples, the best Sn/Sp compromise was at 1.25 OD (Sn 91.5%, Sp 92.4%)
      and for convalescent samples at 0.75 OD (Sn 69.8%, Sp 89.5%). A relatively high
      (stringent) diagnostic cut-off value provides increased diagnostic accuracy with
      high sensitivity and specificity in the majority of cases, while lowering the cut
      off runs the risk of false positivity. This study underlines the need for
      regional assessment of new diagnostic tests according to the level of endemicity
      of the disease given the high levels of residual or cross-reacting antibodies in
      the general population.

PMID- 30274493
TI  - Mycetoma: The Spectrum of Clinical Presentation.
AB  - Mycetoma is a chronic infection, newly designated by the World Health
      Organization (WHO) as a neglected tropical disease, which is endemic in tropical
      and subtropical regions. It follows implantation of infectious organisms, either
      fungi (eumycetomas) or filamentous bacteria (actinomycetomas) into subcutaneous
      tissue, from where infection spreads to involve skin, bone and subcutaneous
      sites, leading to both health related and socioeconomic problems. In common with
      other NTDs, mycetoma is most often seen in rural areas amongst the poorest of
      people who have less access to health care. The organisms form small
      microcolonies that are discharged onto the skin surface via sinus tracts, or that
      can burrow into other adjacent tissues including bone. This paper describes the
      clinical features of mycetoma, as early recognition is a key to early diagnosis
      and the institution of appropriate treatment including surgery. Because these
      lesions are mostly painless and the majority of infected individuals present late
      and with advanced disease, simplifying early recognition is an important public
      health goal.

PMID- 30274495
TI  - Melioidosis in the Philippines.
AB  - The first documented case of melioidosis in the Philippines occurred in 1948.
      Since then, there have been sporadic reports in the literature about travelers
      diagnosed with melioidosis after returning from the Philippines. Indigenous
      cases, however, have been documented rarely, and under-reporting is highly
      likely. This review collated all Philippine cases of melioidosis published
      internationally and locally, as well as unpublished case series and reports from
      different tertiary hospitals in the Philippines. In total, 25 papers and 41 cases
      were identified. Among these, 23 were indigenous cases (of which 20 have not been
      previously reported in the literature). The most common co-morbidity present was
      diabetes mellitus, and the most common presentations were pulmonary and soft
      tissue infections. Most of the cases received ceftazidime during the intensive
      phase, while trimethoprim-sulfamethoxazole was given during the eradication
      phase. The known mortality rate was 14.6%, while 4.9% of all cases were reported
      to have had recurrence. The true burden of melioidosis in the country is not well
      defined. A lack of awareness among clinicians, a dearth of adequate laboratories,
      and the absence of a surveillance system for the disease are major challenges in
      determining the magnitude of the problem.

PMID- 30274496
TI  - Young Adults in Endemic Areas: An Untreated Group in Need of School-Based
      Preventive Chemotherapy for Schistosomiasis Control and Elimination.
AB  - Parasitologic surveys of young adults in college and university settings are not
      commonly done, even in areas known to be endemic for schistosomiasis and soil
      transmitted helminths. We have done a survey of 291 students and staff at the
      Kisumu National Polytechnic in Kisumu, Kenya, using the stool microscopy Kato
      Katz (KK) method and the urine point-of-care circulating cathodic antigen (POC
      CCA) test. Based on three stools/two KK slides each, in the 208 participants for
      whom three consecutive stools were obtained, Schistosoma mansoni prevalence was
      17.8%. When all 291 individuals were analyzed based on the first stool, as done
      by the national neglected tropical disease (NTD) program, and one urine POC-CCA
      assay (n = 276), the prevalence was 13.7% by KK and 23.2% by POC-CCA. Based on
      three stools, 2.5% of 208 participants had heavy S. mansoni infections (>=400
      eggs/gram feces), with heavy S. mansoni infections making up 13.5% of the S.
      mansoni cases. The prevalence of the soil-transmitted helminths (STH: Ascaris
      lumbricoides, Trichuris trichiura and hookworm) by three stools was 1.4%, 3.1%,
      and 4.1%, respectively, and by the first stool was 1.4%, 2.4% and 1.4%,
      respectively. This prevalence and intensity of infection with S. mansoni in a
      college setting warrants mass drug administration with praziquantel. This
      population of young adults is 'in school' and is both approachable and worthy of
      inclusion in national schistosomiasis control and elimination programs.

PMID- 30274494
TI  - Control Strategies for Scabies.
AB  - Scabies is a neglected tropical disease of the skin, causing severe itching and
      stigmatizing skin lesions. Further, scabies leads to impetigo, severe bacterial
      infections, and post-infectious complications. Around 200 million people are
      affected, particularly among disadvantaged populations living in crowded
      conditions in tropical areas. After almost 50 years, research into scabies
      control has shown great promise, particularly in highly-endemic island settings,
      but these findings have not been widely adopted. Newer approaches, utilizing
      ivermectin-based mass drug administration, appear feasible and highly effective.
      Inclusion of scabies in the WHO portfolio of neglected tropical diseases in 2017
      may facilitate renewed opportunities and momentum toward global control. However,
      further operational research is needed to develop evidence-based strategies for
      control in a range of settings, and monitor their impact. Several enabling
      factors are required for successful implementation, including availability of
      affordable drug supply. Integration with existing health programs may provide a
      cost-effective approach to control.

PMID- 30274497
TI  - The Skin-A Common Pathway for Integrating Diagnosis and Management of NTDs.
AB  - Many of the neglected tropical diseases (NTDs) have major skin manifestations.
      These skin-related NTDs or 'skin NTDs' cause significant morbidity and economic
      hardship in some of the poorest communities worldwide. We draw attention to the
      collective burden of skin disease and suggest that the skin be used as a platform
      for the integration of control activities for NTDs. The opportunities for
      integration are numerous, ranging from diagnosis and disease mapping to mass drug
      administration and morbidity management. The dermatology community has an
      important role to play, and will be expected to support research and control
      activities globally.

PMID- 30274498
TI  - The Development of a Mobile Application to Support Peripheral Health Workers to
      Diagnose and Treat People with Skin Diseases in Resource-Poor Settings.
AB  - The high prevalence of skin diseases in resource-poor settings, where health
      workers with sufficient knowledge of skin diseases are scarce, calls for
      innovative measures. Timely diagnosis and treatment of skin diseases, especially
      neglected tropical diseases (NTDs) that manifest with skin lesions, such as
      leprosy, is crucial to prevent disabilities as well as psychological and
      socioeconomic problems. Innovative technological methods like telemedicine and
      mobile health (mHealth) can help to bridge the gap between the burden of skin
      diseases and the lack of capable staff in resource-poor settings by bringing
      essential health services from central level closer to peripheral levels.
      Netherlands Leprosy Relief (NLR) has developed a mobile phone application called
      the 'SkinApp', which aims to support peripheral health workers to recognize the
      early signs and symptoms of skin diseases, including skin NTDs, and to start
      treatment promptly or refer for more advanced diagnostic testing or disease
      management when needed. Further research is needed to determine how greatly
      mHealth in general and the SkinApp in particular can contribute to improved
      health outcomes, efficiency, and cost-effectiveness.

PMID- 30274499
TI  - Hospitalizations and Deaths Associated with Diarrhea and Respiratory Diseases
      among Children Aged 0-5 Years in a Referral Hospital of Mauritania.
AB  - Diarrhea and respiratory diseases are the leading causes of morbidity and
      mortality among <5-year-olds worldwide, but systematic data are not available
      from Mauritania. We conducted a hospital-based retrospective study. Data on
      admissions to Mauritania's National Referral Hospital (the main pediatric
      referral center in the country), due to diarrhea and respiratory diseases, during
      2011-2014, were analyzed. A total of 3695 children <5 years were hospitalized
      during this period; 665 (18.0%) due to respiratory diseases, and 829 (22.4%) due
      to diarrhea. Case fatality rates in the respiratory diseases and diarrhea groups
      were 18.0% (120/665) and 14.1% (117/829), respectively. The highest frequency of
      deaths due to diarrhea occurred in the age group 2-5 years (16/76; 21.0%), and
      due to respiratory diseases in the age group 6-12 months (32/141; 22.6%). We
      conclude that case fatality rates caused by respiratory diseases and diarrhea are
      extremely high in children hospitalized at the National Referral Hospital. These
      data call for intensified efforts to reduce deaths among hospitalized Mauritanian
      children, and also for integrated control measures to prevent and reduce the
      burden of both diseases. Additional studies are needed to show the effectiveness
      of the introduction of vaccination programs for pneumococcal diseases and
      rotavirus infection in the child population, which were launched in November 2013
      and December 2014, respectively.

PMID- 30274500
TI  - Revered but Poorly Understood: A Case Report of Dendroaspis polylepis (Black
      Mamba) Envenomation in Watamu, Malindi Kenya, and a Review of the Literature.
AB  - The black mamba (Dendroaspis polylepis) ranks consistently as one of the most
      revered snakes in sub-Saharan Africa. It has potent neurotoxic venom, and
      envenomation results in rapid onset and severe clinical manifestations. This
      report describes the clinical course and reversal of effects of black mamba
      envenomation in a 13-year-old boy in the Jimba area of Malindi. The victim
      presented to Watamu Hospital, a low resource health facility with labored
      breathing, frothing at the mouth, severe ptosis and pupils non-responsive to
      light. His blood pressure was unrecordable, heart rate was 100 beats per minute
      but thready, his temperature was 35.5  degrees C, and oxygen saturation was 83%.
      Management involved suction to clear salivary secretions, several hours of
      mechanical ventilation via ambu-bagging, oxygen saturation monitoring, and the
      use of South African Vaccine Producers (SAVP) polyvalent antivenom. Subcutaneous
      adrenaline was used to stave off anaphylaxis. The victim went into cardiac arrest
      on two occasions and chest compressions lasting 3-5 min was used to complement
      artificial ventilation. Hemodynamic instability was corrected using IV infusion
      of ringers lactate and normal saline (three liters over 24 h). Adequate
      mechanical ventilation and the use of specific antivenom remain key in the
      management of black mamba envenomation.

PMID- 30274501
TI  - Low Microfilaremia Levels in Three Districts in Coastal Ghana with at Least 16
      Years of Mass Drug Administration and Persistent Transmission of Lymphatic
      Filariasis.
AB  - Ghana has been implementing mass drug administration (MDA) of ivermectin and
      albendazole for the elimination of lymphatic filariasis (LF) since the year 2000,
      as part of the Global Programme to Eliminate Lymphatic Filariasis (GPELF). It was
      estimated that 5-6 years of treatment would be sufficient to eliminate the
      disease. Tremendous progress has been made over the years, and treatment has
      stopped in many disease endemic districts. However, despite the successful
      implementation of MDA, there are districts with persistent transmission. In this
      study we assessed the epidemiology of LF in three adjoining districts that have
      received at least 16 years of MDA. The assessments were undertaken one year after
      the last MDA. 1234 adults and 182 children below the age of 10 years were
      assessed. The overall prevalence of circulating filarial antigen in the study
      participants was 8.3% (95% CI: 6.9-9.9), with an estimated microfilaria
      prevalence of 1.2%. The microfilarial intensity in positive individuals ranged
      from 1 to 57 microfilariae/mL of blood. Higher antigen prevalence was detected in
      males (13.0%; 95% CI: 10.3-16.2) compared to females (5.5%; 95% CI: 4.1-7.2). The
      presence of infection was also highest in individuals involved in outdoor
      commercial activities, with the risks of infection being four- to five-fold
      higher among farmers, fishermen, drivers and artisans, compared to all other
      occupations. Using bednets or participating in MDA did not significantly
      influence the risk of infection. No children below the age of 10 years were found
      with infection. Detection of Wb123 antibodies for current infections indicated a
      prevalence of 14.4% (95% CI: 8.1-23.0) in antigen-positive individuals above 10
      years of age. No antibodies were detected in children 10 years or below.
      Assessment of infection within the An. gambiae vectors of LF indicated an
      infection rate of 0.9% (95% CI: 0.3-2.1) and infectivity rate of 0.5% (95% CI:
      0.1-1.6). These results indicate low-level transmission within the districts, and
      suggest that it will require targeted interventions in order to eliminate the
      infection.

PMID- 30274502
TI  - Control of Communicable Diseases in Human and in Animal Populations: 70th
      Anniversary of the Year of the Birth of Professor Rick Speare (2 August 1947-5
      June 2016).

PMID- 30274503
TI  - Further observations on the fine structure of the infracerebral gland in Nereis
      (Annelida; Polychaeta) - C2 and C3 cells; centripetal and centrifugal fibers.
AB  - The infracerebral gland of Nereis is made up of three types of cells. C1 cells
      are hypertrophied pericapsular elements, whereas C2 and C3 cells have the
      morphological and cytological features of neurosecretory neurons. C2 and C3 cells
      give rise to centripetal "proximal processes" which extend into the brain through
      the midventral pocket formed by delamination of the brain capsule. Their "distal
      processes" terminate within the gland or its immediate vicinity. "Centrifugal
      fibers" arise from nerve cells located within the brain and appear to synapse
      upon the proximal processes of C2 cells in the region of the midventral pocket
      and in the ventral region of the brain. The cytology of C2 and C3 cells suggests
      that they are the source of distinct peptide hormones.

PMID- 30274504
TI  - Change of voltage-gated potassium channel 1.7 expressions in monocrotaline
      induced pulmonary arterial hypertension rat model.
AB  - PURPOSE: Abnormal potassium channels expression affects vessel function,
      including vascular tone and proliferation rate. Diverse potassium channels,
      including voltage-gated potassium (Kv) channels, are involved in pathological
      changes of pulmonary arterial hypertension (PAH). Since the role of the Kv1.7
      channel in PAH has not been previously studied, we investigated whether Kv1.7
      channel expression changes in the lung tissue of a monocrotaline (MCT)-induced
      PAH rat model and whether this change is influenced by the endothelin (ET)-1 and
      reactive oxygen species (ROS) pathways. METHODS: Rats were separated into 2
      groups: the control (C) group and the MCT (M) group (60 mg/kg MCT). A hemodynamic
      study was performed by catheterization into the external jugular vein to estimate
      the right ventricular pressure (RVP), and pathological changes in the lung tissue
      were investigated. Changes in protein and mRNA levels were confirmed by western
      blot and polymerase chain reaction analysis, respectively. RESULTS: MCT caused
      increased RVP, medial wall thickening of the pulmonary arterioles, and increased
      expression level of ET-1, ET receptor A, and NADPH oxidase (NOX) 4 proteins.
      Decreased Kv1.7 channel expression was detected in the lung tissue. Inward
      rectifier channel 6.1 expression in the lung tissue also increased. We confirmed
      that ET-1 increased NOX4 level and decreased glutathione peroxidase-1 level in
      pulmonary artery smooth muscle cells (PASMCs). ET-1 increased ROS level in
      PASMCs. CONCLUSION: Decreased Kv1.7 channel expression might be caused by the ET
      1 and ROS pathways and contributes to MCT-induced PAH.

PMID- 30274505
TI  - Oral findings and its association with prenatal and perinatal factors in
      newborns.
AB  - PURPOSE: This study aimed to determine the frequency of abnormalities in the
      newborn oral cavity and to evaluate the association with prenatal and perinatal
      factors. METHODS: This cross-sectional study evaluated 2,216 newborns. Oral
      findings were assessed in the first 24 hours of life using visual examination.
      Sex, weight, length, gestational age, and medical disorders at birth were
      recorded. Maternal demographic and medical information was also obtained.
      RESULTS: The most common oral findings were Bohn's nodules, Epstein's pearls, and
      dental lamina cysts. Other intraoral findings included odontogenic cysts,
      ankyloglossia, and natal teeth, among others. In logistic regression analyses,
      folic acid consumption during pregnancy was significantly associated with Bohn's
      nodules (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.23-2.55;
      P=0.002), Epstein's pearls (OR, 1.63; 95% CI, 1.14-2.33; P=0.007), and dental
      lamina cysts (OR, 1.45; 95% CI, 1.02-2.05; P=0.038). Moreover, preterm births
      were negatively associated with prevalence of Bohn's nodules (OR, 0.63; 95% CI,
      0.50-0.80; P<=0.0001). Comparison between newborns with and without oral
      inclusion cysts showed that maternal folic acid and iron intake were
      significantly different (P<0.05). CONCLUSION: Maternal folic acid and iron intake
      were associated with the prevalence of oral inclusion cysts.

PMID- 30274506
TI  - Usefulness of the procalcitonin test in young febrile infants between 1 and 3
      months of age.
AB  - PURPOSE: To study the usefulness of the procalcitonin (PCT) test in young febrile
      infants between 1 and 3 months of age. METHODS: We evaluated the medical records
      of 336 febrile infants between 1 and 3 months of age who visited the Emergency
      Department or outpatient department of Samsung Changwon Hospital from May 2015 to
      February 2017, and analyzed the clinical characteristics between infants in the
      serious bacterial infection (SBI) group and non-SBI group. RESULTS: Among the 336
      infants, 38 (11.3%) had definitive SBI (bacteremia, n=3; meningitis, n=1; urinary
      tract infection, n=34). The mean PCT (6.4+/-11.9 ng/mL) and C-reactive protein
      (CRP) level (3.8+/-2.6 mg/dL), and the absolute neutrophil count (ANC) (6,984+/
      4,675) for patients in the SBI group were significantly higher than those for
      patients in the non-SBI group (PCT, 0.3+/-1.2 ng/mL; CRP, 1.3+/-1.6 mg/dL; ANC,
      4,888+/-3,661). PCT had lower sensitivity (43.6%), but higher specificity (92.6%)
      and accuracy (86.9%) than CRP (92.3%, 25.3%, and 33.0%) for identifying SBI. The
      area under the receiver operating characteristic curves (AUCs) for definitive SBI
      were PCT 77.0%, CRP 80.8%, WBC 56.8%, ANC 67.8%, and PLT 48.1%. The AUCs for
      definitive SBI were PCT+CRP 85.4%, PCT+WBC 77.2%, PCT+ANC 81.3%, CRP+WBC 80.1%,
      and CRP+ANC 81.6%. CONCLUSION: Our results suggest that the PCT test or a
      combination of PCT and CRP tests is a more accurate and specific biomarker to
      detect and rule out SBIs.

PMID- 30274508
TI  - Assessing nociception: steps towards intraoperative "full monitoring".

PMID- 30274507
TI  - The changes of prevalence and etiology of pediatric pneumonia from National
      Emergency Department Information System in Korea, between 2007 and 2014.
AB  - PURPOSE: Understanding changes in pathogen and pneumonia prevalence among
      pediatric pneumonia patients is important for the prevention of infectious
      diseases. METHODS: We retrospectively analyzed data of children younger than 18
      years diagnosed with pneumonia at 117 Emergency Departments in Korea between 2007
      and 2014. RESULTS: Over the study period, 329,380 pediatric cases of pneumonia
      were identified. The most frequent age group was 1-3 years old (48.6%) and the
      next was less than 12 months of age (17.4%). Based on International
      Classification of Diseases, 10th revision diagnostic codes, confirmed cases of
      viral pneumonia comprised 8.4% of all cases, pneumonia due to Mycoplasma
      pneumoniae comprised 3.8% and confirmed cases of bacterial pneumonia 1.3%. The
      prevalence of confirmed bacterial pneumonia decreased from 3.07% in 2007 and
      4.01% in 2008 to 0.65% in 2014. The yearly rate of pneumococcal pneumonia also
      decreased from 0.47% in 2007 to 0.08% in 2014. A periodic prevalence of M.
      pneumoniae pneumonia (MP) was identified. CONCLUSION: The increased number of
      patients with pneumonia, bacterial pneumonia, pleural effusion, and empyema in
      2011 and 2013-2014 resulted from an MP epidemic. We provide evidence that the
      frequency of confirmed cases of bacterial pneumonia and pneumococcal pneumonia
      has declined from 2007 to 2014, which can simultaneously reflect the
      effectiveness of the pneumococcal conjugate vaccine.

PMID- 30274509
TI  - Systematic Analysis of Bottlenecks in a Multibranched and Multilevel Regulated
      Pathway: The Molecular Fundamentals of l-Methionine Biosynthesis in Escherichia
      coli.
AB  - To produce chemicals and fuels from renewable resources, various strategies and
      genetic tools have been developed to redesign pathways and optimize the metabolic
      flux in microorganisms. However, in most successful cases, the target chemicals
      are synthesized through a linear pathway, and regular methodologies for the
      identification of bottlenecks and metabolic flux optimization in multibranched
      and multilevel regulated pathways, such as the l-methionine biosynthetic pathway,
      have rarely been reported. In the present study, a systematic analysis strategy
      was employed to gradually reveal and remove the potential bottlenecks limiting
      the l-methionine biosynthesis in E. coli. 80 genes in central metabolism and
      selected amino acids biosynthetic pathways were first repressed or upregulated to
      probe their effects on l-methionine accumulation. The l-methionine biosynthetic
      pathway was then modularized and iteratively genetic modifications were performed
      to uncover the multiple layers of limitations and stepwise improve the l
      methionine titer. The metabolomics data further revealed a more evenly
      distributed metabolic flux in l-methionine biosynthesis pathway of the optimal
      strain and provided valuable suggestions for further optimization. The optimal
      strain produced 16.86 g/L of l-methionine in 48 h by fed-batch fermentation. This
      work is the first to our knowledge to systematically elucidate the molecular
      fundamentals of multilevel regulation of l-methionine biosynthesis. It also
      demonstrated that the systematic analysis strategy can boost our ability to
      identify the potential bottlenecks and optimize the metabolic flux in
      multibranched and multilevel regulated pathways for the production of
      corresponding chemicals.

PMID- 30274510
TI  - Electrochemical-Signal-Amplification Strategy for an Electrochemiluminescence
      Immunoassay with g-C3N4 as Tags.
AB  - Signal amplification for electrochemiluminescence (ECL) has conventionally been
      achieved by employing effective matrixes that can accelerate the electrochemical
      redox processes or carry more electrochemiluminophores. Herein, a convenient
      signal-amplification strategy was proposed for an ECL immunoassay with
      carboxylated g-C3N4 nanosheets (NSs) as tags and carcinoembryonic antigen (CEA)
      as the model target via electrochemically pretreating the substrate: a glassy
      carbon electrode (GCE) modified with a polymerized 2-aminoterephthalic acid (ATA)
      film (GCE/ATA). Bioconjugates of g-C3N4 NSs and the signal CEA antibody (Ab2)
      (i.e., g-C3N4 NS-Ab2) were immobilized on GCE/ATA via a sandwich immunoreaction
      to form GCE/ATA-Ab1-Ag-Ab2-NSs. Electrochemical-impedance spectroscopy and
      potential-resolved ECL characterization proved that GCE/ATA plays an important
      role in the electron-transfer resistance ( Ret) of the GCE/ATA-Ab1-Ag-Ab2-NSs for
      ECL and that successively scanning GCE/ATA-Ab1-Ag-Ab2-NSs from 0 to -1.6 V in
      K2S2O8- and H2O2-containing medium could reduce the Ret and bring out 3.3-times
      enhanced ECL at the 10th scan cycle compared with that of the 1st scan cycle,
      which was about 10.2 times the ECL of the GCE/ATA-Ab1-Ag-Ab2-NSs in medium
      containing merely K2S2O8. Inspired by this, direct and successive scanning of
      GCE/ATA in K2S2O8- and H2O2-containing medium was employed during fabrication,
      which dramatically reduced the Ret of GCE/ATA-Ab1-Ag-Ab2-NSs and brought out
      obviously enhanced ECL responses for selectively determining CEA from 0.1 pg/mL
      to 1 ng/mL, with a detection limit of 3 fg/mL.

PMID- 30274511
TI  - Ionic Ga-Complexes of Alkylidene- and Arylmethylidenemalonates and Their
      Reactions with Acetylenes: An In-Depth Look into the Mechanism of the Occurring
      Gallium Chemistry.
AB  - A new synthetic concept was suggested in the chemistry of substituted
      methylidenemalonates that enables their utilization as 1,2-zwitterionic synthons.
      This strategy is to generate liquid ionic Ga complexes from methylidenemalonates
      and GaHal3 with a strict 3/4 composition and then use them in further synthesis.
      A number of complexes with different metal halides have been synthesized and
      studied in detail. The unique properties of gallium among all metals have been
      demonstrated and explained. On the basis of the discovered new class of gallium
      complexes of methylidenemalonates, a number of novel reactions with acetylenes
      have been elaborated, which are unknown in the conventional chemistry of
      methylidenemalonates. The main demonstrated process is a three-component addition
      to a triple bond involving halide anions, leading to the formation of
      polyfunctional vinyl halides with high E-selectivity. The mechanism has been
      studied experimentally in fine detail. Application of specially optimized 71Ga
      NMR spectroscopy makes it possible to take an in-depth look into the gallium
      chemistry in a new light. In particular, the key participation of GaHal4- anions
      in the occurring transformations has been established.

PMID- 30274512
TI  - Online Gas-Free Electrodialytic KOH Eluent Generator for Ion Chromatography.
AB  - An online gas-free KOH electrodialytic eluent generator (EDG) with two-membrane
      configuration is described for ion chromatography (IC). A central eluent channel
      is separated from two outer regenerant channels bearing KOH solution (or one is
      water) by stacked cation-exchange membranes (sCEMs) and a bipolar membrane (BPM)
      plus stacked CEMs (BPM-sCEMs), in which the anion-exchange membrane (AEM) of BPM
      is facing the central channel (the anode direction). Independent fluid input or
      output ports address all channels. One platinum screen electrode is put in each
      outer channel, and the sCEM side is anode with respect to the cathode of the BPM
      sCEM side. Under the electric field, enhanced water splitting at the intermediate
      layer of BPM will occur, offering hydroxide and hydronium; hydroxide
      electromigrates through AEM into the central channel, while the potassium of KOH
      feed solution at the anode migrates into the central channel to combine with
      hydroxide to form a solution of KOH. Because the central eluent channel is
      spatially isolated from both electrodes, the generated KOH solution is gas-free
      and no gas-removal device is required. More important, the AEM side of BPM is
      contactless with the alkaline solution, nearly avoiding possible AEM degradation
      when immersed into concentrated alkaline solution. This ensures long-term running
      stability of the EDG and high purity of the produced KOH solution (as indicated
      by the typical suppressed background conductance of 0.28 MUS/cm). The EDG has a
      pressure tolerance (at least 21 MPa), and the produced KOH concentration is up to
      101 MUeq/min with near-unity faradaic efficiency. When operated in both isocratic
      and gradient modes, the EDG demonstrates excellent reproducibility, as indicated
      by the retention time of RSD <= 0.08% and the peak area of RSD <= 0.6%. To the
      best of our knowledge, this is the first description of gas-free EDG matched
      conventional IC system.

PMID- 30274513
TI  - Photogeneration of Quinone Methides as Latent Electrophiles for Lysine Targeting.
AB  - Latent electrophiles are nowadays very attractive chemical entities for drug
      discovery, as they are unreactive unless activated upon binding with the specific
      target. In this work, the utility of 4-trifluoromethyl phenols as precursors of
      latent electrophiles, quinone methides (QM), for lysine-targeting is
      demonstrated. These Michael acceptors were photogenerated for specific covalent
      modification of lysine residues using human serum albumin (HSA) as a model
      target. The reactive QM-type intermediates I or II, generated upon irradiation of
      4-trifluoromethyl-1-naphthol (1)@HSA or 4-(4-trifluorometylphenyl)phenol (2)@HSA
      complexes, exhibited chemoselective reactivity toward lysine residues leading to
      amide adducts, which was confirmed by proteomic analysis. For ligand 1, the
      covalent modification of residues Lys106 and Lys414 (located in subdomains IA and
      IIIA, respectively) was observed, whereas for ligand 2, the modification of
      Lys195 (in subdomain IIA) took place. Docking and molecular dynamics simulation
      studies provided an insight into the molecular basis of the selectivity of 1 and
      2 for these HSA subdomains and the covalent modification mechanism. These studies
      open the opportunity of performing protein silencing by generating reactive
      ligands under very mild conditions (irradiation) for specific covalent
      modification of hidden lysine residues.

PMID- 30274514
TI  - Next Generation Histology-Directed Imaging Mass Spectrometry Driven by
      Autofluorescence Microscopy.
AB  - Histology-directed imaging mass spectrometry (IMS) is a spatially targeted IMS
      acquisition method informed by expert annotation that provides rapid molecular
      characterization of select tissue structures. The expert annotations are usually
      determined on digital whole slide images of histological stains where the
      staining preparation is incompatible with optimal IMS preparation, necessitating
      serial sections: one for annotation, one for IMS. Registration is then used to
      align staining annotations onto the IMS tissue section. Herein, we report a next
      generation histology-directed platform implementing IMS-compatible
      autofluorescence (AF) microscopy taken prior to any staining or IMS. The platform
      enables two histology-directed workflows, one that improves the registration
      process between two separate tissue sections using automated, computational
      monomodal AF-to-AF microscopy image registration, and a registration-free
      approach that utilizes AF directly to identify ROIs and acquire IMS on the same
      section. The registration approach is fully automated and delivers state of the
      art accuracy in histology-directed workflows for transfer of annotations (~3-10
      MUm based on 4 organs from 2 species) while the direct AF approach is
      registration-free, allowing targeting of the finest structures visible by AF
      microscopy. We demonstrate the platform in biologically relevant case studies of
      liver stage malaria and human kidney disease with spatially targeted acquisition
      of sparsely distributed (composing less than one tenth of 1% of the tissue
      section area) malaria infected mouse hepatocytes and glomeruli in the human
      kidney case study.

PMID- 30274515
TI  - Synthesis and Characterization of PDMS-PMOXA-Based Polymersomes Sensitive to MMP
      9 for Application in Breast Cancer.
AB  - Cytotoxic compounds used to treat cancer are often associated with adverse
      events. The development of formulations activated by tumor-specific triggers
      would allow a reduction of systemic exposure while maintaining therapeutic
      concentrations in the tumor. One enzyme with proteolytic activity reported to be
      involved in tumor progression and assumed to be enhanced in the tumor environment
      is the matrix metalloproteinase 9 (MMP-9). In our study, we aimed to develop
      surface-modified PDMS-PMOXA polymersomes able to release their cytotoxic payload
      upon digestion by MMP-9. To test the applicability of such a system in breast
      cancer, this tumor entity was assessed for MMP-9 expression, supporting breast
      cancer as a potential target. The surface-modified polymersomes were synthesized
      and formulated resulting in paclitaxel-loaded particles of about 320 +/- 153.15
      nm in size with a surface potential of 0.04 +/- 0.007 mV. After the expression
      and activity of MMP-9 in MCF7 cells were verified, this cell line was used for
      further analysis. Treatment of MCF7 cells with the polymersomes significantly
      reduced cell viability, this effect was abolished after addition of MMP
      inhibitors, suggesting proteolytic activation. In zebrafish embryos, the
      polymersomes were observed in the circulation with some enrichment in liver and
      agglomerates in the caudal veins. Importantly, in zebrafish embryos xenografted
      with mKate2-expressing MCF7 cells, the amount of tumor cells, quantified by
      detecting the copies of the heterologously expressed fluorescent protein,
      significantly decreased after treatment with PDMS-PMOXA-SRL-paclitaxel
      polymersomes. Taken together, our data suggest that polymersomes modified with an
      MMP-9 labile peptide and loaded with paclitaxel can be formulated, and that these
      particles exert pharmacological activity upon enzymatic digestion.

PMID- 30274516
TI  - Stochastic Transition State Theory.
AB  - Kramers's original paper on the diffusion model of chemical reactions was based
      on the consideration that only the barrier region determines the outcome of
      transmission over a barrier. Subsequently it became understood that Kramers's
      approach was identical to variational transition state theory (VTST) and as such
      used only thermodynamic information. Here, using Kramers's philosophy in
      conjunction with perturbation theory and the realization that the dynamics which
      is rate-determining usually occurs in the vicinity of the transition state leads
      to a novel stochastic rate theory in which the momentum change induced by the
      medium is the stochastic variable. A first successful application of the theory
      is to the old and challenging problem of motion over a cusped barrier. This has
      implications for the study of transition path time distributions as well as the
      theory of tunneling via nonadiabatic coupling.

PMID- 30274517
TI  - An NIR-Guided Aggregative and Self-Immolative Nanosystem for Efficient Cancer
      Targeting and Combination Anticancer Therapy.
AB  - Nanosized drug delivery systems based on polymeric structures have been proven to
      be promising approaches for cancer treatments. However, few have been effective
      at selectively targeting cancer cells and releasing drug at desired tumor sites.
      Here, we report a "smart" polymeric nanoplatform, which could actively accumulate
      at tumor sites and dissociate to release encapsulated cargos upon the irradiation
      of a near-infrared (NIR) laser. This nanoplatform composed of a novel amphiphilic
      block copolymer poly(propylene sulfide)-poly( N-isopropylacrylamide- co- N, N
      dimethylacrylamide) (PPS-P(NIPAM- co-DMAA)) formed spherical structures in
      aqueous solution and responded to both oxidants and elevated temperature. Upon
      laser irradiation at 808 nm, the NIR light was efficiently converted to local
      heat by the doxorubicin (DOX) and indocyanine green (ICG) co-loaded micelles for
      enhanced cell uptake and therapeutic efficacy. It showed that the micelles
      effectively accumulated at the tumor sites guided by the application of an NIR
      laser in in vivo studies, exhibiting a 6-time greater and much faster targeting
      effect compared to the nonirradiation group. The effective tumor growth
      inhibition by the drug-loaded micelles upon laser irradiation demonstrated
      significant tumor inhibition without regrowth in 16 days. This micellar
      nanoplatform for precise NIR-guided cancer targeting and combination therapy
      provides a novel and robust strategy for cancer therapy.

PMID- 30274518
TI  - Self-Assembly of Nanocubic Molecular Capsules via Solvent-Guided Formation of
      Rectangular Blocks.
AB  - We investigate the mechanism underlying the self-assembly of gear-shaped
      amphiphilic molecules into a highly ordered nanocubic capsule ("nanocube") in
      aqueous methanol. Simulation results show that the solvent molecules play a
      significant role in the assembly process by directing the primitive intermediates
      to orthogonal/rectangular shapes, thus creating appropriate building blocks for
      cubic assembly while avoiding off-pathway stacked aggregates. Free-energy
      analyses reveal that the interplay of the direct intermonomer interaction and the
      solvent-mediated repulsion between large aromatic cores (via preferential
      solvation of methanol on hydrophobic surfaces) leads to the strong trend for
      perpendicular binding of monomers and hence the solvent-guided formation of
      rectangular blocks. Furthermore, we report the self-assembly simulation of the
      nanocube using replica exchange with solute tempering and demonstrate that the
      simulation can predict a highly ordered nanocapsule structure, assembly
      intermediates, and encapsulated molecules, which helps promote computer-aided
      design of functional molecular self-assemblies in explicit solvent.

PMID- 30274519
TI  - Interfacial Properties of Polyelectrolyte-Surfactant Aggregates at Air/Water
      Interfaces.
AB  - The transport, equilibrium properties, and mechanics of stable, rodlike
      surfactant-polyelectrolyte aggregates, poly(cetyltrimethylammonium vinyl
      benzoate) or pCTVB, are characterized at air/water interfaces for bulk
      concentrations near and below the critical aggregation concentration. The
      surfactant drives the transport to air/water interfaces, while the
      polyelectrolyte provides elasticity to the coated interfaces and appears to
      remain adsorbed after the bulk solution is exchanged with water. The processing
      of interfaces is shown to allow the interfacial tension of the interface to be
      changed significantly while maintaining a high dilatational elasticity. The
      results of this work provide a tool to control interfacial properties through
      design of polyelectrolyte-surfactant complexes.

PMID- 30274520
TI  - Distribution Profiles of Melamine and Its Derivatives in Indoor Dust from 12
      Countries and the Implications for Human Exposure.
AB  - Melamine and its derivatives (i.e., ammeline, ammelide, and cyanuric acid) are
      extensively used in household products, such as furniture, dinnerware, and food
      utensils. Nevertheless, limited information is available on human exposures,
      other than dietary sources, to melamine and its derivatives. In this study, the
      occurrence of melamine and its derivatives was determined, for the first time, in
      341 samples of indoor dust, collected from 12 countries. All of the dust samples
      contained target analytes, with global median concentrations of 1800, 1100, 48,
      and 45 ng/g for melamine, cyanuric acid, ammelide, and ammeline, respectively.
      The total concentrations of melamine and its derivatives varied among countries
      in the following decreasing order: United States (median: 17 000 ng/g) > Japan
      (8400) > China (8000) > South Korea (7300) > Saudi Arabia (4400) > Romania (4300)
      > Greece (3400) > Kuwait (2400) > Vietnam (2300) > Colombia (1300) > Pakistan
      (820) > India (430). Correlation analysis indicated the existence of multiple and
      varied sources for melamine and cyanuric acid. Estimated daily intakes of
      melamine via indoor dust ingestion were at least 2 orders of magnitude below the
      current tolerable daily intake.

PMID- 30274521
TI  - Methionine Promotes Milk Protein and Fat Synthesis and Cell Proliferation via the
      SNAT2-PI3K Signaling Pathway in Bovine Mammary Epithelial Cells.
AB  - Methionine (Met) plays a critical regulatory role in milk production, however,
      the molecular mechanism of action of Met is largely unknown. This study therefore
      aimed to investigate the influence of Met on milk synthesis in and proliferation
      of bovine mammary epithelial cells (BMECs) and explore the underlying mechanism.
      BMECs cultured in fetal bovine serum (FBS) free Dulbecco's modified eagle's
      medium (DMEM)/F-12 medium were treated with Met (0, 0.3, 0.6, 0.9, and 1.2 mM).
      Results showed that Met (0.6 mM) significantly increased milk protein and fat
      synthesis and cell proliferation. Met stimulation also increased mTOR
      phosphorylation and protein expression of SREBP-1c and Cyclin D1. Gene function
      study approaches further revealed that SNAT2 is a key regulator of these
      signaling pathways. PI3K inhibition experiments demonstrated that SNAT2
      stimulates these pathways through regulating PI3K activity, and SNAT2 inhibition
      experiments further revealed that SNAT2 is required for Met to activate PI3K.
      Furthermore, immunofluorescence observation detected that Met stimulates SNAT2
      cytoplasmic expression. Collectively, these findings demonstrate that Met
      positively regulates milk protein and fat synthesis and cell proliferation via
      the SNAT2-PI3K signaling pathway in BMECs.

PMID- 30274522
TI  - Beneficial effects of Saccharomyces cerevisiae RC016 in weaned piglets: in vivo
      and ex vivo analysis.
AB  - Probiotics represents an alternative to replace antibiotics as growth promoters
      in animal feed and are able to control enteric bacterial diseases and to improve
      gut immunity. Saccharomyces cerevisiae RC016 showed previously
      inhibition/coagregation of pathogens) and mycotoxins adsorbent ability (aflatoxin
      B1, ochratoxin A and zearalenone). The aim of this work was to evaluate
      beneficial properties of S. cerevisiae RC016 in a non-inflammatory in vivo model
      in weaned piglets and in an intestinal inflammation ex vivo model induced by the
      mycotoxin deoxynivalenol (DON). Secretory immunoglobulin A (s-IgA) levels,
      intestinal cytokines, goblet cells and production parameters were evaluated in a
      pig model. For the in vivo assays, twelve pigs were weaned at 21 days and
      assigned to two groups: Control (n=6) and Yeast (n=6). Animals received yeast
      strain for three weeks. After 22 days the small intestine was recovered for
      determination of goblet cells and s-IgA. For the ex vivo assay, jejunal explants
      were obtained from 5 weeks old crossbred piglets and treated as follow: (1)
      control; (2) treated for 3 h with 10 MUM DON used as an inflammatory stressor;
      (3) incubated with 107 cfu/ml yeast strain; (4) pre-incubated 1 h with 107 cfu/ml
      yeast strain and then treated for 3 h with 10 MUM DON. CCL20, interleukin (IL)
      1beta, IL-8 and IL-22 gene expression was determined by qPCR. Oral administration
      of S. cerevisiae RC016 increased s-IgA, the number of goblet cells in small
      intestine and all the growth parameters measured. In the ex vivo model, the
      cytokine profile studied showed a potential anti-inflammatory effect of the
      administration of the yeast. In conclusion, S. cerevisiae RC016 is a promising
      candidate for feed additives formulation to improve animal growth and gut immune
      system. This yeast strain could be able to improve the gut health through
      counteracting the weaning-associated intestinal inflammation in piglets.

PMID- 30274523
TI  - "Hotel Refuses Negro Nurse": Gloria Clarke Baylis and the Queen Elizabeth Hotel.
AB  - On 2 September 1964, one day after the Act Respecting Discrimination in
      Employment was introduced in Quebec, Gloria Clarke Baylis, a British-trained
      Caribbean migrant nurse, inquired about a permanent part-time nursing position at
      the Queen Elizabeth Hotel (QEH). In response, she was told that the position had
      already been filled. Less than a year later, Gloria appeared as the key witness
      in Her Majesty the Queen, Complainant v. Hilton of Canada Ltd., Accused, to
      determine whether the QEH violated the new legislation. Drawing on excerpts from
      the court transcript, this article expands and complicates intersectionality as a
      theoretical framework to include other markers of difference. Critical to this
      discussion are two interrelated concerns: first, the connection between Gloria's
      experience at the QEH and Black women's historical relationship to nursing;
      second, how her subjectivity and identity influenced her decision to pursue the
      lawsuit.

PMID- 30274524
TI  - Disappearing Acts: Anguish, Isolation, and the Re-imagining of the Mentally Ill
      in Global Psychopharmaceutical Advertising (1953-2005).
AB  - The visualization of mental illness has attracted substantial attention from
      scholars in recent decades. Due to the invisible nature of mental disorders, this
      work has stressed the importance of representations in shaping perceptions of
      mental illness. In the second half of the 20th century, advertisements for
      psychopharmaceutical medications became important avenues through which mental
      illness was made visible. This article analyzes how drug advertisements portrayed
      mentally ill individuals in medical journal advertisements from 14 countries
      between 1953 and 2005. We argue that a shift in representations occurred in the
      1980s: whereas earlier campaigns were dominated by images of the mentally ill
      suffering in isolation, the post-1980s period was marked by a trend toward
      "positive" imagery, social inclusion, and ordinariness. This shift re-imagines
      the role of psychopharmaceuticals and who might be understood as mentally ill,
      reflecting changes in global marketing and the arrival of the "happiness turn"
      within the pharmaceutical industry.

PMID- 30274525
TI  - Savoir rire entre les lignes : materialisme medical et " hieropsychologie " dans
      la Revue de l'hypnotisme (1887-1910).
AB  - Laughter played a crucial strategic role in the fight against clericalism and
      religion in France during the second half of the 19th century and the first half
      of the 20th century. The cultural output from this polemical use of laughter is
      contrasted with a "scholarly literature," which fought against religion in a
      radically different manner that featured reason facing obscurantism and
      prejudice. Drawing on a study of the contributions dealing with "the psychology
      of religion" or "hieropsychology" published in the Revue de l'hypnotisme, I will
      try to show that there also exists a "scholarly ridicule," the forms, codes, and
      uses of which are characteristic of the anticlerical laughter associated with
      "medical materialism."

PMID- 30274526
TI  - From Improving Egos to Perfecting Smiles: Orthodontics and Psychology, 1945-2000.
AB  - From World War II to the end of 20th century, the types of patients undergoing
      orthodontic treatment and their reasons for doing so changed significantly. In
      the 1950s and 1960s, Canadian parents were told that orthodontics would "cure"
      inferiority complexes and protect children with crooked teeth, especially girls,
      from a life of delinquency and missed opportunities. By the last two decades of
      the 20th century, the consumer health movement and rising incomes empowered
      patients to decide which treatments were right for them, and an increasing number
      of adult patients sought orthodontic treatment to improve their appearance.
      Orthodontists never abandoned their claim that orthodontic treatment could
      improve psychological health, as while health psychologists and other researchers
      increasingly called this into question. But orthodontists did begin to place
      greater emphasis on aesthetics as a reason for treatment, and orthodontics became
      part of a much larger explosion in "cosmetic dentistry" procedures that came to
      include tooth whitening and veneers.

PMID- 30274527
TI  - Mrs. Robinson's Revenge: Pete Seeger, Earl Robinson, and the Medicare Protest
      Song.
AB  - In 1962, Pete Seeger recorded "The Ballad of Doctor Dearjohn" about Canadian
      Medicare and the Saskatchewan doctors' strike of the same year. How had this New
      Yorker, recently relieved of a jail sentence, learned of Medicare in the distant
      prairie province? And why was his song never released? This paper traces the
      ballad's fortunes through the papers of composer Earl Robinson (University of
      Washington) and the archives of the American Medical Association. It is situated
      in the historiography of folk revival and the expatriate adventures of artistic
      Americans persecuted in the McCarthy era.

PMID- 30274528
TI  - Despite Being "Known, Highly Promiscuous and Active": Presumed Heterosexuality in
      the USPHS's STD Inoculation Study, 1946-48.
AB  - The Sexually Transmitted Disease Inoculation Study of the United States Public
      Health Service (USPHS) was a short-term deliberate exposure experiment into the
      prevention of venereal diseases. Between 1946 and 1948, over 1,300 Guatemalan
      prisoners, psychiatric patients, soldiers, and sex workers were exposed to
      syphilis, gonorrhoea, and chancroid. USPHS researchers initially proposed hiring
      sex workers to "naturally" transmit venereal diseases to male subjects who would
      then be given various prophylaxes. The researchers were interested in studying
      the effectiveness of new preventative measures. In other words, the USPHS study
      was designed to transmit venereal diseases heterosexually from an "infected"
      female body to the men who, it was assumed, were sexually isolated subjects.
      However, the researchers did record instances of male-to-male disease
      transmission among their subject populations, instances that challenged the
      presumption of heterosexuality on which the study was based.

PMID- 30274529
TI  - Biotransformation and biosynthesis of natural products.

PMID- 30274531
TI  - The relationship between Home-time, quality of life and costs after ischemic
      stroke: the impact of the need for mobility aids, home and car modifications on
      Home-time.
AB  - PURPOSE: Home-time (the number of days spent at home during the first 3 months
      after stroke) shows a strong association with the modified Rankin scale (mRS). We
      studied whether Home-time was also a determinant of quality-of-life and medical
      care costs after ischemic stroke, and assessed factors delaying discharge home.
      MATERIALS AND METHODS: Five hundred and sixty nine patients participated in a
      retrospective study when returning for an in-person visit after an ischemic
      stroke. Home-time, mRS, EQ-5D-3L, inpatient and outpatient resource utilization,
      use of mobility aids, changes to home and car, comorbidities were recorded.
      RESULTS: Each additional Home-time day was significantly associated with an
      increase in utility of 0.0056 (p < 0.0001) and an in- and outpatient cost saving
      of $99 (p = 0.0158). Requiring extra material support significantly decreased
      Home-time by 76 days (including: requiring home changes: -68 days, car
      alterations: -49 days, needing a wheelchair: -80 days or walker: -71 days,
      needing bed or bath rails: -79 days). This univariable effect was confirmed in
      multivariable analysis when comparing with patients having the same disability
      level without requiring material support. CONCLUSIONS: Home-time is a stroke
      outcome associated with disease severity, healthcare costs and patient wellbeing.
      Streamlining the discharge process for those requiring extra material support may
      lead to cost savings and higher quality-of-life. Implications for rehabilitation
      Delays in discharge from the acute hospital or rehabilitation facility are
      incurred when patients need extra material support in order to return home. Staff
      from the discharging facility should assist families by giving timely information
      on the availability and the cost of wheel chairs and walkers; and explaining and
      planning the need of a stair lift, bed and bath rails as well as car
      modifications. Planning the discharge process with the families will lead to a
      more rapid return home and will result in reduced overall health care costs and
      higher quality of life for the patients.

PMID- 30274530
TI  - Hyperbaric oxygen therapy ameliorates osteonecrosis in patients by modulating
      inflammation and oxidative stress.
AB  - Early stages of avascular necrosis of the femoral head (AVNFH) can be
      conservatively treated with hyperbaric oxygen therapy (HBOT). This study
      investigated how HBOT modulates inflammatory markers and reactive oxygen species
      (ROS) in patients with AVNFH. Twenty-three male patients were treated with two
      cycles of HBOT, 30 sessions each with a 30 days break between cycles. Each
      session consisted of 90 minutes of 100% inspired oxygen at 2.5 absolute
      atmospheres of pressure. Plasma levels of tumor necrosis factor alfa (TNF-alpha),
      interleukin 6 (IL-6), interleukin 1 beta (IL-1beta) and ROS production were
      measured before treatment (T0), after 15 and 30 HBOT sessions (T1 and T2), after
      the 30-day break (T3), and after 60 sessions (T4). Results showed a significant
      reduction in TNF-alpha and IL-6 plasma levels over time. This decrease in
      inflammatory markers mirrored observed reductions in bone marrow edema and
      reductions in patient self-reported pain.

PMID- 30274532
TI  - Contribution assessment of multiparameter optimization descriptors in CNS
      penetration.
AB  - Assessment of the influence of six physicochemical properties used in the
      multiparameter optimization (MPO) approach for chemical penetration of the blood
      brain barrier was carried out by means of application of logistic regression and
      multiple linear regression, using a data set of 578 diverse chemicals. It was
      found that use of an aggregation MPO-score descriptor did not give satisfactory
      results with central nervous system (CNS)/non-CNS classification. Thus an
      application of the MPO approach for CNS penetration is ambiguous. An alternative
      to the MPO approach in this work contains detailed (quantitative) structure
      activity relationship analysis using a number of methods (linear discriminant
      analysis, random forest, support vector machine, Gaussian process). Three
      properties (molecular weight, number of H-bond donors and octanol-water partition
      coefficient) yielded optimal categorical models with modest statistical
      parameters (accuracy 0.730-0.765 for CNS/non-CNS classification). The poor
      statistics of regression models for the common data set suggested the presence of
      subsets with different mechanisms of penetrations. Based on graphic comparison of
      experimental and calculated Cu,b values, subset clusters have satisfactory
      statistics. The regression models obtained allowed the estimation of descriptor
      contributions in log Cu,b. This means that medicinal chemists now have a simple
      additive scheme for at least preliminary quantitative assessment of this
      important pharmacokinetic parameter.

PMID- 30274533
TI  - SAR and QSAR models of cyclooxygenase-1 (COX-1) inhibitors.
AB  - Cyclooxygenase-1 (COX-1) is one isoform of COX, and it is a main target of
      nonsteroidal anti-inflammatory drugs (NSAIDs). It is important to develop
      efficient and selective COX-1 inhibitors. In this work, 12 classification models
      for 1530 cyclooxygenase-1 (COX-1) inhibitors were built by support vector machine
      (SVM), decision tree (DT) and random forest (RF) methods. The best classification
      model (model 1A) was built by SVM with MACCS fingerprints. The classification
      accuracies for the training and test sets were 99.67% and 97.39%, respectively.
      The Matthews correlation coefficient (MCC) of the test set was 0.94. We also
      divided the 1530 COX-1 inhibitors into nine subsets according to their different
      scaffolds using Kohonen's self-organizing map (SOM). In addition, six
      quantitative structure-activity relationship (QSAR) models for 181 COX-1
      inhibitors whose IC50 were measured by enzyme immunoassay were built by multiple
      linear regression (MLR) and SVM. The best QSAR model (model 5A) was built by SVM
      with CORINA Symphony descriptors. The correlation coefficients of the training
      and test sets are 0.93 and 0.84, respectively. The models built in this study can
      be obtained from the authors.

PMID- 30274534
TI  - An Evaluation of SPARC Protein as a Serum Biomarker of Chronic Rhinosinusitis.
AB  - Objective Precision medicine initiatives for chronic rhinosinusitis (CRS)
      management suggest tailoring treatment to the patient's individual disease
      profile; however, serum biomarkers for evaluation of disease activity or
      predicting response to therapy are lacking in CRS. Epithelial-to-mesenchymal
      transition (EMT) has been described as a component of barrier dysfunction in CRS.
      SPARC (secreted protein acidic and rich in cysteine) is a marker of EMT that has
      previously been identified in sinus epithelium by gene expression profiling. We
      wished to determine if SPARC could represent a serum biomarker for CRS by
      verifying (1) if SPARC could be detected in serum, (2) whether levels were
      sensitive to disease burden reduction following surgery, and (3) if it could
      predict response to therapy. Study Design Prospective. Setting Tertiary care
      center. Subjects Patients with CRS undergoing endoscopic sinus surgery (ESS).
      Methods Twenty-six patients undergoing ESS for CRS were prospectively recruited.
      Serum was collected at the time of surgery and 4 months following ESS and SPARC
      level measured using enzyme-linked immunosorbent assay. Postoperative outcome was
      characterized as "remission" or "unfavorable" based on symptomatology and
      endoscopy. Results SPARC could be detected and measured in serum in all subjects.
      Following ESS, SPARC levels decreased by 33% ( P = .005) but did not predict
      evolution at 4 months postsurgery ( P = .94). Conclusion SPARC may be an
      interesting serum biomarker of disease activity in CRS, as it can be reliably
      measured and decreases following successful reduction of disease burden after
      surgery. However, it does not predict post-ESS evolution, suggesting that the
      link between EMT and outcome is not linear.

PMID- 30274536
TI  - Cutting-edge evidence of adjuvant treatments for gastric cancer.
AB  - INTRODUCTION: In recent decades, adjuvant therapy has secured a firm position in
      the treatment of gastric cancer by improving patient prognosis. Currently,
      standard therapy varies between East Asia, Europe and North America due to
      heterogeneities of the tumor, race, medical environment and/or surgical
      procedure. Although adjuvant strategies, proved effective in each region and
      implemented to clinical practice, certain patient populations with advanced
      gastric cancer show recurrence and a fatal prognosis. The development of a
      universal adjuvant therapy with a high efficacy and acceptable adverse events or
      with less toxicity and non-inferiority seems to have become urgent and
      imperative. Areas covered: In this review, we aimed to summarize the current
      knowledge regarding adjuvant therapies for gastric cancer, including
      chemotherapy, chemoradiotherapy and molecular targeted therapy, based on clinical
      trials and to introduce the pivotal ongoing phase III trials. Expert commentary:
      The efficacy of adjuvant therapy to prevent recurrence remains insufficient
      although several trials have shown a significant benefit in patients with
      localized advanced gastric cancer. The development of more effective and
      universal multimodal adjuvant therapy is required.

PMID- 30274535
TI  - Carbonic anhydrase inhibition with a series of novel benzenesulfonamide-triazole
      conjugates.
AB  - We report the synthesis and characterisation of a novel series of triazole
      benzenesulfonamide derivatives, which incorporate the general pharmacophore
      associated with carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The synthesised
      compounds were tested in vitro against four human carbonic anhydrase (hCA, EC
      4.2.1.1) isozymes, hCA I, hCA II, hCA IV and hCA IX. The obtained results showed
      that the tumour-associated hCA IX was the most sensitive to inhibition with the
      synthesised derivatives, with the triazolo-pyridine benzenesulfonamides 14, 16
      and 17 being the most effective inhibitors. Some selected compounds were chosen
      for a single dose anti-proliferative activity testing against a panel of 57 human
      tumour cell lines and show some anti-proliferative activity ex vivo.

PMID- 30274537
TI  - Validation of a videogrammetry technique for analysing American football helmet
      kinematics.
AB  - Professional American football games are recorded in digital video with multiple
      cameras, often at high resolution and high frame rates. The purpose of this study
      was to evaluate the accuracy of a videogrammetry technique to calculate
      translational and rotational helmet velocity before, during and after a helmet
      impact. In total, 10 football impacts were staged in a National Football League
      (NFL) stadium by propelling helmeted 50th percentile male crash test dummies into
      each other or the ground at speeds and orientations representative of concussive
      impacts for NFL players. The tests were recorded by experienced sports film crews
      to obtain video coverage and quality typically available for NFL games. A
      videogrammetry procedure was used to track the position and rotation of the
      helmet throughout the relevant time interval of the head impact. Compared with
      rigidly mounted retroreflective marker three dimensional (3-D) motion tracking
      that was concurrently collected in the experiments, videogrammetry accurately
      calculated changes in translational and rotational velocity of the helmet using
      high frame rate (two cameras at 240 Hz) video (7% and 15% error, respectively).
      Low frame rate (2 cameras at 60 Hz) video was adequate for calculating pre-impact
      translational velocity but not for calculating the translational or rotational
      velocity change of the helmet during impact.

PMID- 30274539
TI  - Improvements in landing biomechanics following anterior cruciate ligament
      reconstruction in adolescent athletes.
AB  - Motion analysis offers objective insight into biomechanics, rehabilitation
      progress and return to sport readiness. This study examined changes in three
      dimensional movement patterns during drop jump landing between early and late
      stages of rehabilitation in adolescent athletes following anterior cruciate
      ligament reconstruction (ACLR). Twenty-four athletes (58% female; mean age 15.4
      years, SD 1.2) with unilateral ACLR underwent motion analysis testing 3-6 months
      and again 6-10 months post-operatively. Kinematics and kinetics were compared
      between visits and between limbs using repeated measures ANOVA. The operative
      side exhibited lower vertical ground reaction force, less energy absorption and
      lower sagittal external moments at the knee and ankle, and lower peak
      dorsiflexion angles compared with the non-operative side regardless of visit.
      Between visits, hip and knee flexion increased bilaterally, as well as hip
      flexion moments and energy absorption. During early rehabilitation following
      ACLR, adolescent athletes reduced flexion and loading of the knee and ankle on
      their operative limb. Motion and loading increased over time, particularly at the
      hip, but remained reduced at the knee and ankle 6-10 months post-operatively.

PMID- 30274538
TI  - Benzofuran-appended 4-aminoquinazoline hybrids as epidermal growth factor
      receptor tyrosine kinase inhibitors: synthesis, biological evaluation and
      molecular docking studies.
AB  - A series of 2-arylbenzo[b]furan-appended 4-aminoquinazoline hybrids were prepared
      and evaluated for cytotoxicity in vitro against the human lung cancer (A549),
      colorectal adenocarcinoma (Caco-2), hepatocellular carcinoma (C3A) and cervical
      cancer (HeLa) cell lines. Compounds 10d and 10j exhibited significant
      cytotoxicity against the C3A and Caco-2 cell lines and induced apoptosis in these
      cell lines. Likewise, compounds 10d and 10e exhibited significant inhibitory
      activity towards epidermal growth factor receptor-tyrosine kinase phosphorylation
      (IC50 values of 29.3 nM and 31.1 nM, respectively) against Gefitinib (IC50 = 33.1
      nM). Molecular docking of compounds 10 into EGFR-TK active site suggests that
      they bind to the region of EGFR like Gefitinib does. [Formula: see text].

PMID- 30274540
TI  - Effect of Postoperative Xylitol Nasal Irrigation on Patients with Sinonasal
      Diseases.
AB  - Objective To examine the effect of xylitol nasal irrigation in a large sample
      size of patients who had undergone nasal surgery. Study Design Double-blinded
      randomized controlled crossover study. Setting Tertiary referral center. Methods
      The study included 100 patients with sinonasal disease who underwent endoscopic
      sinus surgery (ESS), septoplasty, or both concurrently. To identify patients with
      allergic sensitization, serum-specific immunoglobulin E levels were measured.
      Nasal symptoms were evaluated with the NOSE (Nasal Obstruction Symptoms
      Evaluation) and SNOT-20 (Sino-Nasal Outcome Test-20) and via visual analog scale
      (VAS) scores. Results In the ESS group (n = 34), the general nasal symptom score
      evaluated by the SNOT-20 showed significantly greater improvement in the xylitol
      group versus the saline group ( P = .022). VAS symptom scores for sneezing ( P =
      .003), headache ( P = .02), and facial pain ( P = .037) were also more improved
      in the xylitol group. In the septoplasty group (n = 39), the VAS score for nasal
      stuffiness showed a significantly greater improvement in the xylitol group when
      compared with the saline irrigation group ( P = .001). Among the patients with
      allergic sensitization (n = 31), rhinorrhea symptoms improved significantly more
      in the xylitol group than in the saline group ( P = .024). The preference survey
      showed that more than half of the patients in each surgical group preferred
      xylitol irrigation. Conclusion We found that xylitol nasal irrigation was useful
      in postoperative ESS and septoplasty care. For patients with allergic
      sensitization, rhinorrhea showed greater improvement in the xylitol group than in
      the saline group.

PMID- 30274541
TI  - Treatment of Tonsillar Carcinoma following Nononcologic Tonsillectomy: Efficacy
      of Transoral Robotic Revision Tonsillectomy.
AB  - Objective To evaluate whether transoral robotic surgery (TORS) is a suitable
      treatment approach for patients diagnosed with tonsillar carcinoma after a
      standard palatine tonsillectomy. Study Design Retrospective cohort study. Setting
      Tertiary care medical center. Subjects and Methods Patients who underwent TORS at
      the University of Washington from 2010 to 2017 (n = 150) were identified. All
      patients who were diagnosed with tonsillar carcinoma following a nononcologic
      tonsillectomy and subsequently underwent TORS radical tonsillectomy were included
      (n = 14). Tumor stage-matched subjects (n = 44) were included who did not undergo
      standard tonsillectomy prior to TORS. Our primary outcome was final margin
      status. Secondary outcomes were presence of residual tumor, receipt and dose of
      postoperative adjuvant therapy, disease-free survival (DFS), and disease-specific
      survival. Patients with <6 months of follow-up following definitive treatment
      were excluded from survival analyses. Results Final margin status was clear in
      all subjects. Residual tumor was not identified in 13 of 14 (92.9%) prior
      tonsillectomy subjects following TORS radical tonsillectomy. Seven of 14 (50%)
      prior-tonsillectomy subjects and 12 of 44 (27.3%) TORS-matched subjects did not
      require adjuvant therapy due to favorable pathology. Among subjects who received
      post-TORS radiation therapy (RT) at our institution, RT dose reduction was
      achieved in 3 of 4 (75%) prior-tonsillectomy subjects and 21 of 24 (87.5%) TORS
      matched subjects. Ten of 14 (71.4%) prior-tonsillectomy subjects and 31 of 44
      (70.5%) TORS-matched subjects avoided post-TORS chemotherapy. DFS was not
      significantly different ( P = .87) between prior-tonsillectomy and TORS-matched
      groups, and no subjects died of related disease. Conclusions Patients diagnosed
      with tonsillar carcinoma following a prior nononcologic standard palatine
      tonsillectomy are suitable candidates for revision surgery with TORS radical
      tonsillectomy.

PMID- 30274542
TI  - Measurement of bend sprinting kinematics with three-dimensional motion capture: a
      test-retest reliability study.
AB  - Sprint velocity decreases on the bend when compared with the straight, therefore
      understanding technique during bend sprinting could have important implications
      for aiding race performance. Few bend sprinting studies have used optoelectronic
      cameras to investigate kinematic variables. Limited published evidence regarding
      the reliability of marker sets in conditions representative of elite bend
      sprinting makes model selection difficult. Therefore, a test-retest protocol was
      conducted to establish the reliability and minimum detectable difference of a
      lower limb and trunk marker set during bend sprinting (radius: 36.5 m). Six
      participants completed five, 60 m trials at maximum effort, with data collected
      at 38-45 m. This was repeated 2-7 days later. Spatio-temporal (e.g., contact
      time) and kinematic variables (e.g., peak joint angles) were evaluated. Intra
      class correlation coefficients (ICC) were used to determine the between- and
      within-day reliability. Between-day reliability (ICC 3, k) was fair to excellent
      for all variables. Compared to between-day, within-day reliability demonstrated
      stronger agreement for the majority of variables. Thus, same-day data collection
      is preferable. It has been established that the marker set is reliable for future
      use. In addition, the minimal detectable difference was calculated which serves
      as useful reference for future research in bend sprinting.

PMID- 30274543
TI  - Reaction time and muscle activation patterns in elite and novice athletes
      performing a taekwondo kick.
AB  - Fractionated reaction time can be used to determine distinct epochs known as pre
      motor, response and movement times (MTs) of a reaction time task. The purpose of
      this study was to compare elite and novice athletes performing a taekwondo kick
      in terms of the fractionated reaction time and electromyography (EMG) activation
      patterns of the muscles of the striking lower limb and the lower back. We
      hypothesised that the pre-motor time, response time (RT) and MT would be the
      shorter for elite athletes compared to novices. We collected data on 13 elite and
      10 novice athletes when performing a roundhouse kick. The experiment included EMG
      electrodes placed on five low back and lower extremity muscles and an
      electrogoniometer placed on the kicking knee. We found that pre-motor time was
      shorter and the RT was longer for elite athletes than novice athletes. Moreover,
      the integrated EMG of the main knee extensor does not differ between groups
      though other leg and trunk muscles do. The results allow coaches and teachers to
      understand this particular taekwondo kicking movement which could ultimately
      improve the technique in order to establish training and teaching goals.

PMID- 30274544
TI  - Human Papillomavirus-Associated Oropharyngeal Cancer: Patterns of Nodal Disease.
AB  - Objective To characterize patterns of neck lymph node (LN) metastases in human
      papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma,
      represented by p16 positivity (p16+OPSCC). Study Design Case series with chart
      review. Setting Tertiary care center. Subjects and Methods Neck dissection (ND)
      specimens of nonirradiated p16+OPSCC patients were analyzed for frequencies of
      clinically evident and occult LNs by neck level. Local, regional, and distant
      recurrences were reviewed. Results Seventy p16+OPSCC patients underwent primary
      site transoral robotic surgery and 82 NDs of varying levels. Metastatic
      pathologic LNs were found at the following frequencies: 0% (0/28) in level I,
      75.6% (62/82) in level II with 57.4% (35/61) in level IIA and 13.1% (8/61) in
      level IIB, 22.0% (18/82) in level III, 7.0% (5/71) in level IV, and 6.3% (1/16)
      in level V. The level V LN was clinically evident preoperatively. Five of 21
      (23.8%) elective NDs contained occult LNs, all of which were in level II and
      without extranodal extension. Twenty-seven (38.6%) patients underwent adjuvant
      radiation; 19 (27.1%) patients underwent adjuvant chemoradiation. With a mean
      follow-up of 29 months, 3 patients had developed recurrences, with all but 1
      patient still alive. All patients who recurred had refused at least a component
      of indicated adjuvant treatment. Conclusions For p16+OPSCC, therapeutic NDs
      should encompass any levels bearing suspicious LNs and levels IIA-B, III, and IV,
      while elective NDs should be performed and encompass at least levels IIA-B and
      III. These selective ND plans, followed by indicated adjuvant treatment, are
      associated with a low nodal recurrence rate.

PMID- 30274545
TI  - Effect of downhill running grade on lower extremity loading in female distance
      runners.
AB  - Hill running is often used as a foundational training mechanism to build strength
      and speed. Distance runners in particular are at an increased likelihood of
      encountering steep hills during training runs. There is limited research
      regarding downhill running, and there is no research available on the
      biomechanics of females specifically during downhill running. The purpose of this
      study was to quantify the differences in loading when running downhill at
      different grades compared to a level surface in female distance runners to
      determine the potential risk for injury. Fifteen female distance runners (age:
      23.5 +/- 4.9 y), who ran 56.3 +/- 20.9 km a week participated in this study.
      Participants ran on a force-instrumented treadmill at 4.0 m/s for 2 min at 0%, 
      5%, -10%, -15%, and -20% grades, with 5 min of rest between conditions. Study
      findings showed increased impact forces (p < 0.001), and increased loading rates
      (p < 0.001) with increasing downhill grades compared to level. These results
      indicate a significantly greater risk of overuse injury to the lower extremity
      with steeper downhill grades. Individuals need to be aware of these risks to plan
      and implement training programmes that will increase performance while minimising
      injury risk.

PMID- 30274546
TI  - Evaluation of Acellular Bilayer Silk Fibroin Grafts for Onlay Tracheoplasty in a
      Rat Defect Model.
AB  - Objective To assess the efficacy of acellular bilayer silk fibroin (BLSF) grafts
      to repair full-thickness tracheal defects and to compare the performance with
      conventional porcine small intestinal submucosa (SIS) implants. Study Design A
      prospective controlled animal trial in a rat model of onlay tracheoplasty.
      Setting Pediatric medical center. Subjects and Methods Tracheal reconstruction of
      adult Sprague-Dawley rats was performed with BLSF (n = 38) or SIS (n = 32)
      matrices for up to 3 months of implantation. Functional evaluations of repaired
      conduits as well as histologic, immunohistochemical, and histomorphometric
      analyses of neotissues were assessed. Results Prior to scheduled euthanasia,
      survival rates of rats receiving BLSF or SIS grafts were >=94%, with no clinical
      signs of airway obstruction observed over the course of the study. Micro-computed
      tomography analysis revealed that the mean percentage of stenosis was <20% in
      both implant groups. BLSF and SIS grafts supported formation of pseudostratified
      ciliated columnar epithelium by 1 week postoperatively; however, each matrix
      failed to promote de novo chondrogenesis by 3 months following repair.
      Conclusions BLSF scaffolds can be used for reconstruction of rat tracheal patch
      defects with functional outcomes comparable to those of SIS matrices.

PMID- 30274547
TI  - From fundamentals to applications of bioelectrocatalysis: bioelectrocatalytic
      reactions of FAD-dependent glucose dehydrogenase and bilirubin oxidase.
AB  - In this review, I present the main highlights of my works in the development of
      bioelectrocatalysis, which can be used in widespread applications, particularly
      for the design of biosensor and biofuel cells. In particular, I focus on research
      progress made in two key bioelectrocatalytic reactions: glucose oxidation by
      flavin adenine dinucleotide-dependent glucose dehydrogenase and oxygen reduction
      by bilirubin oxidase. I demonstrate the fundamental principles of
      bioelectrocatalysis and the requirements for enhancing the catalytic performance,
      including the choice of a mediator of redox reactions, immobilization, and
      electrode materials. These methods can allow for achieving control of the
      bioelectrocatalytic reaction, thereby overcoming obstacles toward their
      industrial applications.

PMID- 30274548
TI  - Peripheral Vestibular System Histopathologic Changes following Head Injury
      without Temporal Bone Fracture.
AB  - Objective Vestibular symptoms such as dizziness and vertigo are common after head
      injury and may be due to trauma to the peripheral vestibular system. The
      pathophysiology of peripheral vestibular symptoms following head injury without
      temporal bone (TB) fracture, however, is not well understood. Herein, we
      investigate the histopathology of the peripheral vestibular system of patients
      who sustained head injury without a TB fracture. Study Design Otopathology study.
      Setting Otopathology laboratory. Subjects and Methods TB of subjects with a
      history of head injury without TB fractures were included and evaluated by light
      microscopy. Specimens were assessed for qualitative and quantitative
      characteristics, such as number of Scarpa's ganglion cells in the superior and
      inferior vestibular nerves, vestibular hair cell and/or dendrite degeneration in
      vestibular end organs, presence of vestibular hydrops, and obstruction of the
      endolymphatic duct. Results Five cases (n = 5 TBs) had evidence of vestibular
      pathology. There was a decrease of 48.6% (range, 40%-59%) in the mean count of
      Scarpa's ganglion cells as compared with that of normative historical age-matched
      controls. Moderate to severe degeneration of the vestibular membranous labyrinth
      was identified in the posterior, superior, and lateral canals in several cases
      (50%, n = 4 TBs). The maculae utriculi and sacculi showed mild to severe
      degeneration in 2 cases. Additional findings include vestibular hydrops (25%, n =
      2 TBs) and blockage of the endolymphatic duct (n = 1 TB). Conclusions
      Otopathologic analysis of patients with a history of head injury without TB
      fracture demonstrated peripheral vestibular otopathology. Future studies are
      necessary to determine if otopathology findings are directly attributable to head
      injury.

PMID- 30274549
TI  - Effect of exercise order with barbell and machine modalities on upper body volume
      load and myoelectric activity.
AB  - The purpose of this study was to investigate the influence of exercise order on
      volume load (VL) and myoelectric activation (EMG) during the bench press (BP),
      military press (MP) and close-grip bench press (CGBP) exercises executed with a
      barbell and Smith machine. Twelve men experienced in resistance training
      performed four different exercise sessions in randomised order. Each session
      consisted of four sets of a given exercise order: O1 = CGBP + MP + BP with
      barbell; O2 = inverse O1 with barbell, O3 = same O1 with Smith Machine; O4 = same
      O2 with Smith machine. EMG was assessed for the Clavicular head pectoralis major
      (PMC), anterior deltoid (AD), triceps brachii long head (TBLH) and biceps brachii
      (BB). Results showed that VL in BP was affected by exercise order, independent of
      the mode (p < 0.05). However, the CGBP showed higher VL in O1. Moreover, when the
      BP was positioned last in the sequence (O1 and O3), myoelectric activity was
      higher for PMC, AD and TBLH (p < 0.05). Findings were similar in the CGBP (PMC
      and TBLH), but for the AD (Smith machine > barbell, p < 0.05). Therefore, it
      appears that the order and modes of exercises influence both volume load and
      myoelectric activation patterns during multiple set of resistance training.

PMID- 30274550
TI  - Event-specific impact test protocol for ice hockey goaltender masks.
AB  - Goaltenders in the sport of ice hockey are at high risk for concussions from
      falls to the ice, player collisions and puck impacts. However, current methods
      used to certify helmets only consider head accelerations for drop tests which may
      not describe all common injury mechanisms relating to concussion. The purpose of
      this study was to describe the characteristics of 3 events associated with
      concussions for ice hockey goaltenders. A helmeted medium National Operating
      Committee on Standards for Athletic Equipment (NOCSAE) headform was impacted
      under conditions representing 3 injury events. Three impact locations' velocities
      were selected for each event based on video analysis of real-world concussive
      events. Peak resultant linear acceleration, rotational acceleration and
      rotational velocity of the headform were measured. The University College Dublin
      Brain Trauma Model (UCDBTM) was used to calculate maximum principal strain (MPS)
      and von Mises stress in the cerebrum. Each impact event produced a unique dynamic
      response and brain stress and strain values. This demonstrates that a single
      impact event (i.e. falls) cannot adequately describe all impact events. As a
      result, impact protocols which assess multiple impact events such as the protocol
      described in this study should be used to evaluate ice hockey goaltender masks.

PMID- 30274551
TI  - Engineering of Corynebacterium glutamicum as a prototrophic pyruvate-producing
      strain: Characterization of a ramA-deficient mutant and its application for
      metabolic engineering.
AB  - To construct a prototrophic Corynebacterium glutamicum strain that efficiently
      produces pyruvate from glucose, the effects of inactivating RamA, a global
      regulator responsible for activating the oxidative tricarboxylic acid (TCA)
      cycle, on glucose metabolism were investigated. DeltaramA showed an increased
      specific glucose consumption rate, decreased growth, comparable pyruvate
      production, higher formation of lactate and acetate, and lower accumulation of
      succinate and 2-oxoglutarate compared to the wild type. A significant decrease in
      pyruvate dehydrogenase complex activity was observed for DeltaramA, indicating
      reduced carbon flow to the TCA cycle in DeltaramA. To create an efficient
      pyruvate producer, the ramA gene was deleted in a strain lacking the genes
      involved in all known lactate- and acetate-producing pathways. The resulting
      mutant produced 161 mM pyruvate from 222 mM glucose, which was significantly
      higher than that of the parent (89.3 mM; 1.80-fold).

PMID- 30274552
TI  - Knee joint coordination during single-leg landing in different directions.
AB  - Knee joint coordination during jump landing in different directions is an
      important consideration for injury prevention. The aim of the current study was
      to investigate knee and hip kinematics on the non-dominant and dominant limbs
      during landing. A total of 19 female volleyball athletes performed single-leg
      jump-landing tests in four directions; forward (0 degrees ), diagonal (30 degrees
      and 60 degrees ) and lateral (90 degrees ) directions. Kinematic and ground
      reaction force data were collected using a 10-camera Vicon system and an AMTI
      force plate. Knee and hip joint angles, and knee angular velocities were
      calculated using a lower extremity model in Visual3D. A two factor repeated
      measures ANOVA was performed to explore limb dominance and jump direction.
      Significant differences were seen between the jump directions for; angular
      velocity at initial contact (p < 0.001), angular velocity at peak vertical ground
      reaction force (p < 0.001), and knee flexion excursion (p = 0.016). Knee
      coordination was observed to be poorer in the early phase of velocity-angle plot
      during landing in lateral direction compared to forward and diagonal directions.
      The non-dominant limb seemed to have better coordination than the dominant limb
      during multi-direction jump landing. Therefore, dominant limbs appear to be at a
      higher injury risk than non-dominant limbs.

PMID- 30274553
TI  - Strong development of research based on national quality registries in Sweden.
AB  - The aim of the present paper is to describe how the use of national quality
      registries (NQRs) for research has evolved over the past decade in Sweden. All
      Swedish NQRs have reported their scientific activity (publications per year in
      peer-reviewed scientific journals) to the Swedish Association of Local
      Authorities and Regions since 2009, and the present report is based on available
      data from 2009-2016. The yearly number of publications of the 69 registries
      active in 2009 has increased from 121 to 496 in 2016. Seventeen of these
      registries published more than 10 papers in 2016; however, 12 NQRs did not
      publish any papers in 2016. An additional 77 papers were published in 2016 by the
      34 NQRs started after 2009. In summary, there has been a strong development of
      quality registry-based research in Sweden over the last decade. However, there is
      still room for further increase of the use of research based on NQRs in Sweden.

PMID- 30274554
TI  - Depressive Disorder in Thyroid Cancer Patients after Thyroidectomy: A
      Longitudinal Follow-up Study Using a National Cohort.
AB  - Objective The present study compared the frequency of depressive disorder in
      patients with thyroid cancer who had undergone thyroidectomy with the frequency
      in control individuals. Study Design Retrospective population-based cohort study.
      Setting This study used data from the Korean Health Insurance Review and
      Assessment Service-National Sample Cohort. Subject and Methods A total of 3609
      participants with thyroid cancer who had undergone thyroidectomy between 2003 and
      2011 were enrolled in this study and matched 1:4 with 14,436 control participants
      by age, sex, income, and region of residence. The cumulative incidence of
      postoperative depressive disorder was evaluated over a period of 10 years after
      the thyroidectomies and compared with the incidence in controls. Depressive
      disorder was diagnosed by a psychiatrist. Results The incidence of depressive
      disorder was significantly higher in the thyroid cancer with thyroidectomy group
      than in the controls up to postoperative year 1. A subgroup analysis showed the
      same higher incidence of depressive disorder in the thyroid cancer group than
      controls for up to 1 year after operations in young adult (<=44 years old),
      female, urban, and low-income groups. However, the incidence was elevated only in
      the year of the thyroidectomies themselves in middle-aged and older, rural, and
      high-income groups. Conclusion Patients with thyroid cancer who undergo
      thyroidectomy have depressive disorder more frequently than normal controls.
      However, the frequency of depressive disorder after thyroidectomy recovers in a
      shorter period in middle-aged or older, high-income, and rural-dwelling patients,
      compared to younger, low-income, and urban-dwelling patients.

PMID- 30274555
TI  - Inventory of chytrid diversity in two temporary forest ponds using a multiphasic
      approach.
AB  - Food webs in temporary forest ponds are driven by decomposition of terrestrial
      inputs. Chytrid fungi are important components of the fungal community, degrading
      leaf litter in streams reliant on terrestrial inputs and in lake ecosystems where
      they may stabilize the food web. However, little is known about chytrid fungi in
      temporary forest ponds. We inventoried the chytrid diversity present in two
      temporary forest ponds via light microscopy of baited samples and ion
      semiconductor (Ion Torrent) sequencing of environmental DNA. We quantified trends
      of chytrid alpha and beta diversity as a function of spatial and temporal
      factors. A total of 59 chytrid taxa were detected throughout the study. Beta
      diversity exhibited variation across the sampled months for both the entire
      fungal community as well as for chytrids alone. Shifts in community composition
      were also apparent, although diversity metrics and composition patterns did not
      meet adjusted P values. The results of this study highlight the diversity of
      chytrid fungi in temporary forest ponds and the need for further studies on the
      spatial and temporal dynamics of chytrid species.

PMID- 30274556
TI  - Intellectual disability in Irish prisoners: systematic review of prevalence.
AB  - Purpose While individuals with an intellectual disability form a significant
      minority in the worldwide prison population, their healthcare needs require
      specialist attention. In Ireland, services for prisoners with intellectual
      disabilities need development. However, there is little substantive data
      estimating the prevalence of intellectual disabilities within the Irish prison
      system. The paper aims to discuss these issues. Design/methodology/approach The
      authors systematically review published data relating to the prevalence of
      intellectual disabilities in prisons in the Republic of Ireland. The authors
      searched four databases, governmental websites and corresponded with experts.
      Findings Little published data were elicited from searches except for one
      nationwide cross-sectional survey which reflected a higher prevalence than
      reported in international studies. Studies from forensic mental health
      populations are narrated to contextualise findings. Originality/value This study
      found that there is little data to accurately estimate the prevalence of
      intellectual disabilities in the Irish prison system and the limited data
      available suggests that this is likely to be higher than international estimates.
      The authors highlight the need for further research to accurately estimate
      prevalence in this jurisdiction, alongside the need to develop screening and care
      pathways for prisoners with an intellectual disability.

PMID- 30274557
TI  - Development of healthcare facility standards for Thai female inmates.
AB  - Purpose The purpose of this paper is to develop and evaluate the Standards of
      Healthcare Facility for Thai Female Inmates (SHF-TFI) through healthcare service
      improvement. Design/methodology/approach This research and quality improvement
      project was comprised of three phases. Surveying healthcare facilities and in
      depth interviews with female inmates as well as prison nurses were employed in
      Phase I. Expert reviews and public hearing meetings were used for developing the
      SHF-TFI in Phase II. Satisfaction questionnaires, focus group interviews of the
      female inmates, and in-depth interviews with nurses and prison wardens were
      utilized to evaluate feasibility and effectiveness of SHF-TFI implementation in
      Phase III. Findings The SHF-TFI was elaborated in order to be more specific to
      the context of the correctional institutes and correspond with healthcare as to
      the needs of female inmates. It was divided into three main aspects:
      administrative standards, health service standards and outcome standards. After
      implementation, nurses reflected on the feasibility and benefits of the SHF-TFI
      on the organizations, inmates and nurses. The female inmates perceived remarkable
      improvement in the healthcare services including physical activity promotion and
      screening programs for non-communicable diseases, the physical environment and
      sufficiency of medical equipment. Moreover, the pregnant inmates and incarcerated
      mothers with children shared their views on better antenatal and child
      developmental care, as well as availability of baby supplies. Originality/value
      The findings support the feasibility and effectiveness of the SHF-TFI for quality
      care improvement and applicability of the Bangkok Rules in women's correctional
      institutes.

PMID- 30274558
TI  - Drug injection within prison in Kyrgyzstan: elevated HIV risk and implications
      for scaling up opioid agonist treatments.
AB  - Purpose Within-prison drug injection (WPDI) is a particularly high HIV risk
      behavior, yet has not been examined in Central Asia. A unique opportunity in
      Kyrgyzstan where both methadone maintenance treatment (MMT) and needle-syringe
      programs (NSP) exist allowed further inquiry into this high risk environment. The
      paper aims to discuss these issues. Design/methodology/approach A randomly
      selected, nationally representative sample of prisoners within six months of
      release in Kyrgyzstan completed biobehavioral surveys. Inquiry about drug
      injection focused on three time periods (lifetime, 30 days before incarceration
      and during incarceration). The authors performed bivariate and multivariable
      generalized linear modeling with quasi-binomial distribution and logit link to
      determine the independent correlates of current WPDI. Findings Of 368 prisoners
      (13 percent women), 109 (35 percent) had ever injected drugs, with most (86
      percent) reporting WPDI. Among those reporting WPDI, 34.8 percent had initiated
      drug injection within prison. Despite nearly all (95 percent) drug injectors
      having initiated MMT previously, current MMT use was low with coverage only
      reaching 11 percent of drug injectors. Two factors were independently correlated
      with WPDI: drug injection in the 30 days before the current incarceration
      (AOR=12.6; 95%CI=3.3-48.9) and having hepatitis C infection (AOR: 10.1; 95%CI=2.5
      41.0). Originality/value This study is the only examination of WPDI from a
      nationally representative survey of prisoners where both MMT and NSP are
      available in prisons and in a region where HIV incidence and mortality are
      increasing. WPDI levels were extraordinarily high in the presence of low uptake
      of prison-based MMT. Interventions that effectively scale-up MMT are urgently
      required as well as an investigation of the environmental factors that contribute
      to the interplay between MMT and WPDI.

PMID- 30274559
TI  - The profile of prisoners with tuberculosis in Japan.
AB  - Purpose Although globally, prisoners are considered one of the vulnerable groups
      to tuberculosis (TB), little is known about the situation of TB in prison setting
      in Japan. The purpose of this paper is to examine the characteristics of TB among
      prisoners in Japan. Design/methodology/approach Records of TB patients from one
      medical prison were analyzed in terms of general demographic characteristics,
      clinical manifestations, risk factors and delay in diagnosis and in initiating
      treatment, and compared with data from the national TB surveillance and other
      published data on health of inmates, where appropriate. Continuous variables were
      compared using student independent samples t-test. Proportions were compared
      using chi2 or Fisher exact test as appropriate. Kaplan-Meier survival analysis
      was conducted to determine the time from entry to prison institution to diagnosis
      of TB. Findings A total of 49 patients were analyzed. The mean age was 49.5 (+/
      14.3) and 69.4 percent were males. Being unemployed and homeless prior to
      incarceration, and several co-morbidities were potential risk factors for TB (
      p<0.01). Analysis of diagnosis and treatment delay showed that 16.1 percent of
      smear positive patients took more than a week to be placed on treatment after
      being diagnosed of TB. Approximately 50 percent of the patients were diagnosed
      within four months of entering the prison institution. Practical implications
      Several potential risk factors identified suggest the need to strengthen
      screening for specific sub-groups within the prison population, such as those
      with poor socio-economic status and co-morbidities, as well as to consider the
      possible role of systematic screening for latent TB infection. Originality/value
      This study presents some important data to help understand the profile of TB
      patients in prisons in Japan, as well as showing that a detailed epidemiological
      analysis of existing records can provide useful insight.

PMID- 30274560
TI  - Prisoner health status at three rural Haitian prisons.
AB  - Purpose Little is known about the health status of prisoners in low-income
      countries. In Haiti, prisons typically lack adequate medical care, clean water
      and food, though some prisoners receive additional food from visitors. The
      purpose of this paper is to characterize the physical and mental health of
      Haitian prisoners in three select prisons and examine the effects of having
      visitors and length of detention on health status. The authors hypothesized that
      prisoners with more visitors and shorter detention times would have better
      overall health status. Design/methodology/approach The authors conducted a cross
      sectional study of 290 male inmates in three regional prisons in Haiti. Data were
      collected on prisoners' sociodemographic characteristics, number of visitors,
      length of detention, body mass index (BMI), self-reported physical and mental
      health status, and food insecurity. Findings Overall, prisoners at all three
      prisons had poor health outcomes. Prisoners with more visitors were significantly
      less likely to be underweight and more likely to have a higher BMI, better self
      reported physical function and lower levels of food insecurity. The length of
      incarceration was negatively associated with physical function and self-rated
      health, but positively associated with BMI. These results suggest that prisoners
      who do not receive supplemental food from visitors are at increased risk for food
      insecurity and poor nutritional and physical health status. Originality/value
      These findings demonstrate the importance of supplemental food from visitors in
      stabilizing prisoner health in Haiti and emphasize the need for the provision of
      adequate nutrition to all prisoners. This study also suggests that policies that
      reduce incarceration times could improve health status among prisoners.

PMID- 30274561
TI  - Socio-demographic characteristics as correlates of psychological distress.
AB  - Purpose The purpose of this paper is to assess the level of psychological
      distress of offenders newly brought into prison custody in a Nigerian prison and
      investigate the relationship with socio-demographic and penal characteristics.
      Design/methodology/approach A cross-sectional study involving 236 new prison
      entrants who were assessed for psychological distress using the 12-item General
      Health Questionnaire (GHQ-12) and the Hospital Anxiety and Depression Scale
      (HADS). Findings A total of 267 prison inmates were newly brought to prison
      custody over a three-month period. Out of this, 236 (88.4 per cent) of them
      participated in the study. Majority of the inmates were males 225 (95.3 per
      cent), awaiting-trial inmates 208 (88.1 per cent), single 144 (61 per cent),
      Christian 224 (94.9 per cent), first time offenders 218 (92.4 per cent) and
      charged with violent offences 136 (57.6 per cent). Majority of the inmates scored
      above cut-off points on the GHQ-12 and the HADS. In total, 157 (66.5 per cent) on
      HADS anxiety subscale, 201 (85.2 per cent) on HADS depression subscale and 199
      (84.3 per cent) on GHQ-12. Significant relationship was observed between GHQ-12
      "caseness", prison category and type of offence. Prison situation and type of
      offence were significantly associated with HADS depression subscale, whereas age
      was associated with HADS anxiety subscale. Research limitations/implications Some
      limitations were encountered in the course of the study. First, the study relied
      on self-report questionnaires for collection of data. Second, information given
      by the respondents could neither be corroborated by family members, who were not
      present during the interview, nor by the officers and men of the Nigeria Prisons
      Service, who knew little or nothing about the respondents. Participants in this
      study had spent maximum of three days in prison during the interview, thus
      certain levels of distress within three days after incarceration may not entail
      "caseness" in the sense of the presence of a psychiatric disorder. Therefore
      assessment over a longer period is needed. Practical implications Screening
      prison inmates on reception into prison custody provides a vista of opportunity
      to identify mental health problems and socio-demographic and forensic correlates
      of psychological distress among new entrants into prison custody. This will
      facilitate early identification and management of prison inmates with health
      needs. Health screening on reception will also help in identifying the various
      penal or forensic characteristics of prison inmates, which will be put into
      consideration during selection of appropriate rehabilitation and reformation
      activities that best fit a particular prison inmate. Early screening of prison
      inmates upon reception in the prison will also help in identifying prison inmates
      who have high risk of suicide and self-harm, thus preventing cases of death that
      may arise as a result of these mental health problems. Findings from this study
      will also enrich the body of knowledge on mental health problems of prison
      inmates entering the prison; this will also help the criminal justice system in
      decision making, especially with emphasis on psychological evaluation of prison
      inmates before dispensing judgment. On the part of the prison authority, the
      prison inmates identified to have psychological distress and some forensic
      characteristics can be properly classified, and kept in cells that will not
      aggravate their distress. Finally, this is the first study of prison inmates on
      reception into Enugu Maximum Security Prison, Enugu State Nigeria. The
      implication of this is that findings from this research will form a baseline on
      which further research on prison inmates upon reception in the prison can be
      conducted. Originality/value This study demonstrated that prison inmates are
      faced with high level of psychological distress during their early days in
      prison, and that some socio-demographic and forensic variables had significant
      association with psychological distress as itemised in Tables III and IV .
      Therefore, screening new inmates on prison reception will help in early
      identification and treatment of vulnerable groups. This will also help in proper
      classification and allocation into appropriate cells of prison inmates by the
      prison authority.

PMID- 30274562
TI  - Modeling the role of fomites in a norovirus outbreak.
AB  - Norovirus accounts for a large portion of the gastroenteritis disease burden, and
      outbreaks have occurred in a wide variety of environments. Understanding the role
      of fomites in norovirus transmission will inform behavioral interventions, such
      as hand washing and surface disinfection. The purpose of this study was to
      estimate the contribution of fomite-mediated exposures to infection and illness
      risks in outbreaks. A simulation model in discrete time that accounted for hand
      to-porous surfaces, hand-to-nonporous surfaces, hand-to-mouth, -eyes, -nose, and
      hand washing events was used to predict 17 hr of simulated human behavior.
      Norovirus concentrations originated from monitoring contamination levels on
      surfaces during an outbreak on houseboats. To predict infection risk, two dose
      response models (fractional Poisson and 2F1 hypergeometric) were used to capture
      a range of infection risks. A triangular distribution describing the conditional
      probability of illness given an infection was multiplied by modeled infection
      risks to estimate illness risks. Infection risks ranged from 70.22% to 72.20% and
      illness risks ranged from 21.29% to 70.36%. A sensitivity analysis revealed that
      the number of hand-to-mouth contacts and the number of hand washing events had
      strong relationships with model-predicted doses. Predicted infection risks ranged
      from 21.29% to 70.36%, overlapping with leisure setting and environmental attack
      rates reported in the literature. In the outbreak associated with the viral
      concentrations used in this study, attack rates ranged from 50% to 86%. This
      model suggests that fomites may have accounted for 25% to 82% of illnesses in
      this outbreak. Fomite-mediated exposures may contribute to a large portion of
      total attack rates in outbreaks involving multiple transmission modes. The
      findings of this study reinforce the importance of frequent fomite cleaning and
      hand washing, especially when ill persons are present.

PMID- 30274563
TI  - Development and psychometric testing of an instrument to measure women's
      perceptions of unplanned pregnancy.
AB  - A woman's decision to continue or terminate an unplanned pregnancy is affected by
      a broad range of contextual and cognitive factors. The identification of women's
      perceptions of unplanned pregnancy is crucial for health care providers to be
      able to offer supportive care and counselling. The aim of this study was to
      develop an instrument to accurately measure women's perceptions of unplanned
      pregnancy: the Women's Perceptions of Unplanned Pregnancy Questionnaire. The
      instrument was developed using a methodological framework guided by Waltz et al.
      (2010). A conceptual model of the designed instrument emerged from the
      qualitative study using a content analysis approach conducted in Tabriz, Iran.
      Participants were recruited using convenience sampling method between June 2016
      and July 2017. Participants were a sample of married Iranian women between the
      ages of 15 and 49 who had experienced an unplanned pregnancy, either unwanted or
      mistimed, within the last 3 months. Women with an established diagnosis of a
      psychological disorder were excluded from the study. The psychometric properties
      of the instrument were assessed using face, content, concurrent and construct
      validations. To evaluate face validity, qualitative and quantitative (item impact
      score) methods were used. The content validity was assessed by fifteen panel
      experts. In addition, concurrent validity of the designed instrument was tested
      using the Persian version of the Cambridge Worry Scale and the Spielberger State
      Trait Anxiety Inventory. The construct validity was calculated by using the
      exploratory factor analysis method. Data were collected from questionnaires
      completed by 310 eligible women. Analysis of the data using exploratory factor
      analysis yielded 31 items in a unique six-factor structure. The instrument was
      found to have high internal consistency (Cronbach's alpha=0.88) and adequate
      reliability (Intraclass Correlation Coefficient=0.89). A clearer understanding of
      women's perceptions of unplanned pregnancy may enhance reproductive services and
      interventions.

PMID- 30274564
TI  - Impact of prenatal and postnatal maternal environment on nephron endowment, renal
      function and blood pressure in the Lewis polycystic kidney rat.
AB  - Maternal insufficiency during fetal development can have long-lasting effects on
      the offspring, most notably on nephron endowment. In polycystic kidney disease
      (PKD), variability in severity of disease is observed and maternal environment
      may be a modifying factor. In this study, we first established that in a rodent
      model of PKD, the Lewis polycystic kidney (LPK) rat's nephron numbers are 25%
      lower compared with wildtype animals. We then investigated the effects of
      prenatal and postnatal maternal environment on phenotype and nephron number. LPK
      pups born from and raised by homozygous LPK dams (control) were compared with LPK
      pups cross-fostered onto heterozygous LPK dams to improve postnatal environment;
      with LPK pups born from and raised by heterozygous LPK dams to improve both
      prenatal and postnatal environment and with LPK pups born from and raised by
      Wistar Kyoto-LPK heterozygous dams to improve both prenatal and postnatal
      environment on a different genetic background. Improvement in both prenatal and
      postnatal environment improved postnatal growth, renal function and reduced blood
      pressure, most notably in animals with different genetic background. Animals with
      improved postnatal environment only showed improved growth and blood pressure,
      but to a lesser extent. All intervention groups showed increased nephron number
      compared with control LPK. In summary, prenatal and postnatal environment had
      significant effect in delaying progression and reducing severity of PKD,
      including nephron endowment.

PMID- 30274565
TI  - Relative validity of brief-type self-administered diet history questionnaire
      among very old Japanese aged 80 years or older.
AB  - OBJECTIVE: Dietary questionnaires for assessing dietary intakes among populations
      of individuals aged 80 years or older (the very old) are very limited. We
      examined the relative validity of forty-three nutrients and twenty-seven food
      groups estimated by a brief-type self-administered diet history questionnaire
      (BDHQ) targeting very old Japanese, using semi-weighed dietary records (DR) as a
      reference. DESIGN: Between June and August 2012 and between June 2015 and
      February 2016, a three-day non-consecutive DR (at two-week intervals) and a BDHQ
      were completed. SETTING: Tokyo, the capital prefecture of Japan. SUBJECTS: Eighty
      very old Japanese (thirty-six men and forty-four women) aged 82-94 years.
      RESULTS: The median intakes of 40-70 % of the crude and energy-adjusted nutrients
      estimated by the BDHQ were significantly different from those estimated by the
      DR. The median Spearman's correlation coefficient of nutrient intakes between the
      BDHQ and the DR was 0.39-0.46. About half (48-56 %) of the food groups were
      significantly different in terms of the median intakes estimated by the BDHQ and
      the DR in crude and energy-adjusted values. The median Spearman's correlation
      coefficient between the BDHQ and the DR was 0.45-0.48. CONCLUSIONS: Acceptable
      Spearman's correlations (>=0.3) were obtained for many dietary intakes among the
      very old Japanese population. The BDHQ is a good candidate for epidemiological
      studies among very old Japanese, although, for some nutrients and food groups,
      the difficulty of estimating accurate median intakes is one of the limitations
      for the tool. Further efforts to enhance the validity of the BDHQ for very old
      populations are needed.

PMID- 30274566
TI  - Mental illness in primary care: a narrative review of patient, GP and population
      factors that affect prescribing rates.
AB  - BACKGROUND: Mental illness poses a large and growing disease burden worldwide.
      Its management is increasingly provided by primary care. The prescribing of
      psychotropic drugs in general practice has risen in recent decades, and variation
      in prescribing rates has been identified by a number of studies. It is unclear
      which factors lead to this variation.AimTo describe the variables that cause
      variation in prescribing rates for psychotropic drugs between general practices.
      METHODS: A narrative review was conducted in January 2018 by searching electronic
      databases using the PRISMA statement. Studies investigating causal factors for
      variation in psychotropic prescribing between at least two general practice sites
      were eligible for inclusion. RESULTS: Ten studies met the inclusion criteria.
      Prescribing rates varied considerably between practices. Positive associations
      were found for many variables, including social deprivation, ethnicity, patient
      age and gender, urban location, co-morbidities, chronic diseases and GP
      demographics. However studies show conflicting findings, and no single regression
      model explained more than 57% of the variation in prescribing
      rates.DiscussionThere is no consensus on the factors that most predict
      prescribing rates. Most research was conducted in countries with central
      electronic databases, such as the United Kingdom; it is unclear whether these
      findings apply in other healthcare systems. More research is needed to determine
      the variables that explain prescribing rates for psychotropic medications.

PMID- 30274567
TI  - Evaluation of the TRANSIA(r)PLATE Staphylococcal Enterotoxins Kit for the
      Detection of Staphylococcal Enterotoxins in Selected Foods.
AB  - The TRANSIA(r) PLATE Staphylococcal Enterotoxins enzyme immunoassay (EIA) was
      validated according to AOAC INTERNATIONAL guidelines for validating qualitative
      binary chemistry and microbiological methods. Five food matrixes were analyzed to
      determine the probability of detection (POD) for staphylococcal enterotoxins
      (SE), including SEA, SEB, SEC1, SEC2, SEC3, SED, and SEE, by the TRANSIA PLATE
      Staphylococcal Enterotoxins EIA. The food matrixes tested were food types
      implicated in staphylococcal enterotoxin outbreaks and included raw milk cheese,
      liquid infant formula, eclairs, ready-to-eat ham, and canned mushrooms. Cheese
      and infant formula were tested with and without dialysis/concentration. The
      infant formula was also tested by an independent laboratory. Each food matrix was
      inoculated with specific toxins at low levels to yield fractional recoveries
      (0.015-0.20 ng/g of food) for POD analysis. One hundred percent recovery was
      achieved at concentrations ranging from <0.10 ng/g to 0.25 ng/g of toxin in the
      various food matrixes. At the same time, 50 Staphylococcus aureus strains known
      to produce toxins and 30 non-toxin producing bacteria (including 22
      Staphylococcus strains) were grown and tested. All the SE toxin-producing strains
      yielded positive results and all of the exclusivity strains were negative.
      Robustness studies showed that changes in sample volume, sample pH, and EIA assay
      temperature had no significant effect on performance. Stability studies showed
      that kits stored for 12+ months performed as well as newly made kits. This assay
      has been approved as a Performance Tested MethodSM.

PMID- 30274568
TI  - Baseline characteristics of gay and bisexual men in a HIV pre-exposure
      prophylaxis demonstration project with equity quotas in Auckland, New Zealand.
AB  - Background: In New Zealand, pre-exposure prophylaxis (PrEP) should target gay and
      bisexual men (GBM), and equity is an important principle. Baseline
      characteristics of GBM offered PrEP in a demonstration project with an enrolment
      quota of 50% non-Europeans are described. Methods: An open-label, single-arm
      treatment evaluation study design ('NZPrEP') was used. The settings were four
      publicly funded sexual health clinics in Auckland in 2017. The study population
      was 150 GBM recruited from clinics, community sources and social media.
      Participants self-completed an online questionnaire about PrEP awareness,
      attitudes and sexual risk behaviour in the last 3 months. Baseline
      characteristics are described and examined to determine whether these were
      associated with PrEP initiation status (self-referral vs doctor/nurse
      recommendation). Results: In total, 150 GBM of whom half (52%) were non-European,
      including 21.3% Maori, 19.3% Asian and 8.7% Pacific, were enrolled into the
      study. Two-thirds (65.3%) self-referred for PrEP and one-third (34.7%) were
      recommended PrEP by the doctor/nurse. Participants reported a high number of male
      condomless receptive anal intercourse partners (MenAICLR) (median 3, range 0-50),
      with 10% reporting 10 or more MenAICLR and 45.3% reporting group sex. In the
      previous year, 65.3% had a sexually transmissible infection (STI); 18% had rectal
      chlamydia or gonorrhoea at enrolment. Almost half (47.7%) had recently used drugs
      with sex, including 8.1% who used methamphetamine. Participants recommended PrEP
      had lower education, lived less centrally and had a higher STI prevalence than
      PrEP self-referrers, but their risk behaviour was similar. Conclusions: Early
      PrEP adopters in New Zealand have high HIV risk. Demonstration projects should
      consider equity mechanisms so that minorities can participate meaningfully.

PMID- 30274569
TI  - ?

PMID- 30274570
TI  - [Intra-operative continuous non-invasive blood pressure monitoring].
AB  - Intra-operative hypotension is associated with increased risk of 30-day mortality
      and organ ischaemia. Thus, a reliable monitoring of blood pressure is desirable.
      New clinical studies indicate, that monitoring of middle arterial pressure with
      continuous non-invasive monitoring during stable haemodynamic conditioning
      provides accurate changes in blood pressure. The potential of continuous non
      invasive monitoring is promising, but not fully developed.

PMID- 30274571
TI  - [Use of compression stockings during flights].
AB  - Flights longer than four hours pose a risk of venous thromboembolism in the
      general population, and the risk increases when additional risk factors are
      present. Compression stockings have proven beneficial on deep as well as
      superficial vein thrombosis and oedema during long-haul flights, without causing
      side effects or discomfort. However, no data exist for flights shorter than four
      hours. Passengers can use compression stockings as general prophylaxis, and this
      should be recommended based on an assessment of endogenous risk factors and the
      duration of the travel.

PMID- 30274573
TI  - [Mediastinal cystic component as cause of deviating growth in a ten-month-old
      boy].
AB  - We present a case report of a ten-month-old boy, who was referred due to
      deviating growth and recurrent respiratory tract infections. Computed tomography
      of the thorax showed two large, cystic components in the mediastinum. He
      underwent surgical removal of the cysts. Pathological examination confirmed the
      diagnosis lymphatic malformation. This case illustrates that intrathoracic tumors
      such as lymphatic malformations, although rare, should be considered in children
      with deviating growth curves and respiratory problems. Rather than continuous
      symptomatic treatment children with symptoms early in life should be prompted in
      further investigations.

PMID- 30274572
TI  - [Diagnosis and treatment of paranoid and schizophrenia-like psychosis in elderly
      patients].
AB  - Research supports theories on valid differences between early-onset schizophrenia
      (EOS), which persists through life, versus late-onset schizophrenia. We
      differentiate between schizophrenia, late-onset schizophrenia (LOS), very late
      onset schizophrenia-like psychosis (VLOSLP) and paranoid psychosis in the
      elderly. While LOS may resemble EOS, VLOSLP may resemble neurodegenerative
      disorders such as Parkinson's disease and Alzheimer's disease. In this review, a
      treatment guideline is proposed.

PMID- 30274574
TI  - [Treatment limitations or discontinuation in patients with benign pulmonary
      diseases].
AB  - The decision to limit or discontinue treatment is a difficult issue, which all
      physicians will face. Timely communication with information on treatment
      possibilities and limitations, respectful listening to patients' and informal
      caregivers' wishes and early palliation is recommended in a stable phase. In some
      situations, it is better to stop life-prolonging treatment and optimise quality
      of life in patients with benign pulmonary diseases. Decision on treatment
      limitations or discontinuation is best taken at a conference and should be based
      on the patient's wishes, the disease stage and progression and potential
      reversible components.

PMID- 30274575
TI  - [Allergic reactions to local anaesthetics].
AB  - Local anaesthetics (LA) are frequently used, but allergy to LA is very rare. It
      can only be verified in about 1% of the patients referred with suspected allergy.
      Reactions may be due to vasovagal or toxic reactions, allergies to additives or
      other products used during administration. Suspicion of allergy should be
      investigated to rule out or confirm allergy. In case of allergy to LA, search of
      a safe alternative ensures the patients future ability to receive LA treatment.
      The investigation method depends on, whether a type I- or type IV reaction is
      suspected.

PMID- 30274576
TI  - ?

PMID- 30274577
TI  - ?

PMID- 30274578
TI  - [Congenital uterine anomalies and their association with fertility and pregnancy
      outcomes].
AB  - Congenital uterine anomalies (CUAs) are present in up to 10% of all women. Data
      suggest that women with CUAs are at higher risk of recurrent spontaneous
      abortions and adverse pregnancy outcomes. It is still debated whether these women
      have impaired fertility. The complication rate is likely to be overrepresented
      and assumedly many women with CUAs have normal reproduction and uneventful
      pregnancies. In women with CUAs and infertility or numerous spontaneous abortions
      surgical treatment should be considered.

PMID- 30274579
TI  - [Human consciousness in health and disease].
AB  - Functional neuroimaging, electroencephalography and clinical examination are
      essential to understand the many facets of disorders of consciousness. Yet, it is
      still not widely known that patients exist who are clearly conscious but unable
      to show it owing to complete loss of motor output, a condition which has been
      termed cognitive motor dissociation. In this review, the mechanisms of normal and
      impaired consciousness are discussed, and current theories of consciousness, as
      well as specific clinical signs, which are essential to discern the state of
      consciousness in a given patient, are highlighted.

PMID- 30274580
TI  - [Benign scrotal diseases].
AB  - Scrotal diseases can be categorised in different ways: Are the patients young or
      old, or is the condition acute or chronic? Few organs are as easily accessible as
      scrotum. Nevertheless, it can be difficult to make a correct diagnosis especially
      in chronic patients. This review divides scrotal diseases in two groups: acute
      and non-acute diseases. Relevant diseases are described with symptoms, clinical
      findings and treatment.

PMID- 30274581
TI  - [Education of healthcare personal may reduce consequences of low health
      literacy].
AB  - Low health literacy is a growing concern affecting up to 20% of the Danish
      population. Low health literacy is defined by difficulties related to
      understanding health information and ability to engage with healthcare providers.
      Research has explored a variety of interventions to address the issue of low
      literacy. This study describes that educational curricula including lessons and
      practicing in didactics and health literacy may improve doctors' knowledge and
      approach towards this group of patients and indicates that healthcare providers
      generally can benefit from education in health literacy.

PMID- 30274582
TI  - [Newborn with aplasia cutis caused by epidermolysis bullosa].
AB  - Epidermiolysis bullosa (EB) is a rare group of genetic disorders, which are
      characterised by bullae and erosions on skin and mucosa. This case report
      describes a patient, who was born at full term without any complications. Both
      crurae were affected by aplasia cutis. Upon birth, the newborn was wrapped in a
      soft blanket, and prophylactic antibiotic treatment was started along with
      analgesics. Large bullae were punctured with a sterile needle, and erosions were
      treated with non-adherent wound dressings and special bandages. Gloves and shoes
      were custom-made. Autosomal recessive dystrophic EB was genetically confirmed,
      and the child was followed regularly by an EB-team.

PMID- 30274583
TI  - [Examination for osteoporosis in patients with chronic obstructive pulmonary
      disease].
AB  - Patients with chronic obstructive pulmonary disease (COPD) are at risk of
      developing osteoporosis, as the COPD in itself as well as continued smoking and
      treatment with systemic corticosteroid all increase the risk of developing
      osteoporosis. Other risk factors for osteoporosis are low vitamin D levels,
      malnutrition and physical inactivity. All patients who have risk factors in the
      form of severe COPD, and all patients with COPD in active treatment with systemic
      corticosteroid and/or other risk factors should be examined with a DEXA-scan.
      Treatment of osteoporosis in patients with COPD does not differ from general
      recommendations.

PMID- 30274584
TI  - ?

PMID- 30274585
TI  - [Treatment of heart failure in patients with reduced left- ventricular ejection
      fraction].
AB  - Treatment of heart failure with reduced ejection fraction has undergone an
      enormous development over the latest three decades resulting in lower mortality.
      Standard treatment now includes use of angiotensin-converting-enzyme (ACE)
      inhibitors, beta blockers and mineralocorticoid receptor antagonists. Diuretics
      are still the cornerstone in the symptomatic treatment of fluid retention.
      Combined angiotensin II receptor blockade and neprilysin inhibition is a new
      treatment option instead of ACE-inhibition for selected patients. Cardiac
      resynchronisation therapy and prophylactic implantable cardiac defibrillators
      further reduce mortality.

PMID- 30274586
TI  - [Heart failure often accompanies diabetes mellitus].
AB  - There are 320,000 diabetes patients in Denmark. Heart failure (HF) is a major
      cardiovascular complication to diabetes mellitus with increasing prevalence. HF
      occurs 2-4 times more frequently in diabetes patients, but patients may go
      undiagnosed for years. Diabetes patients typically suffer from diastolic
      dysfunction caused by myocardial hyper-trophy and "stiffness" of the left
      ventricle. This frequent finding has prompted the term "diabetic cardiomyopathy".
      Echocardiography is a key examination in diagnosing HF and may be warranted to a
      greater degree in diabetes patients at particular risk.

PMID- 30274587
TI  - [Rehabilitation and palliative care in cardiovascular diseases in Denmark].
AB  - An increasing number of Danes are living, and dying, with cardiovascular disease.
      There is good evidence for the impact of cardiac rehabilitation on coronary heart
      disease, heart failure and symptomatic peripheral arterial disease. However, more
      high-quality research is needed into a wider range of cardiac diseases including
      rehabilitation following cardiac arrest, and palliative care for patients with
      advanced heart disease. In this review it is discussed how to improve the quality
      of care and identify the direction of future research and development.

PMID- 30274588
TI  - [Cholesterol-lowering treatment with PCSK9-inhibitors].
AB  - Monoclonal antibodies inhibiting proprotein convertase subtilisin-kexin type 9
      constitute a new class of lipid-lowering drugs. Currently, evolocumab and
      alirocumab are marketed. A recent cardiovascular outcome study with evolocumab
      has shown a cardiovascular (CV) event reduction of 15% in high-risk individuals
      at very low levels of low-density lipoproteins. The adverse event profile up to
      two years is mild. Treatment is very costly, and data on CV endpoints are still
      limited. Treatment is restricted to patients at very high risk of getting CV
      diseases and on a maximal tolerated statin and ezetimibe treatment in addition to
      dietary intervention.

PMID- 30274589
TI  - [Recurrence of venous thromboembolism].
AB  - Recurrence of venous thromboembolism (VTE) is seen in approximately one third of
      the patients after discontinuation of therapy with anticoagulants. The duration
      of treatment seems to be of minor importance, as several studies have shown the
      same recurrence rate over years after treatment for three months and up to 24
      months. In patients with reversible risk factors, three months of treatment seems
      to be sufficient. Treatment duration should be determined by physicians with
      special expertise in risk factors for VTE recurrence and bleeding complications.

PMID- 30274590
TI  - [Transcatheter aortic valve implantation in Denmark].
AB  - During the latest decade, transcatheter aortic valve implantation (TAVI) has
      evolved from being indicated only in patients with severe aortic stenosis and
      prohibitive or high surgical risk, to be an alternative to surgical aortic valve
      replacement in patients with intermediate surgical risk. Improvements of the peri
      procedural management have resulted in marked reduction of complications and an
      increasing number of patients treated with TAVI every year in Denmark. By a
      minimalist approach, TAVI can be performed in local anesthaesia, with same day
      mobilisation and discharge within few days, without affecting the safety.

PMID- 30274591
TI  - [Patent foramen ovale closure in patients with apoplexia].
AB  - Epidemiological studies have shown a larger prevalence of patent foramen ovale
      (PFO) in patients with cryptogenic ischaemic stroke (CIS) than in patients
      without CIS. In 2017, three randomised clinical trials showed a beneficial effect
      of PFO closure in patients with CIS. Among patients with CIS and PFO, those who
      underwent PFO closure, had a lower risk of stroke recurrence than those treated
      with antithrombotic therapy alone. In this review, we analyse the existing
      evidence and set up suggestions for future recommendations for PFO closure in
      patients with CIS.

PMID- 30274592
TI  - [Precision cardiology].
AB  - Cardiology relies on a huge amount of data derived from clinical observations,
      case-specific considerations and randomised controlled trials. At best, medical
      intervention relieves symptoms and reduces disease consequences or complications.
      Rarely, it redirects the cause. However, an accelerated array of opportunities
      within a digital and molecular discourse may mark a medical era which
      acknowledges individual variation rather than accepts a pragmatic pooling of
      similarities. This review aims at providing a brief overview of academic
      achievements, clinical considerations and translational perspectives related to
      precision cardiology.

PMID- 30274594
TI  - Maintaining the legacy.

PMID- 30274596
TI  - Commentaries and Response to: Robinson, Bevelander, Field, and Jones (2018)
      "Methodological and reporting quality in laboratory studies of human eating
      behavior".

PMID- 30274595
TI  - Leaving the light on illuminating the NMA path to health equity - Past, present
      and future.

PMID- 30274593
TI  - Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing
      cells.
AB  - Transcription of protein coding genes is accompanied by recruitment of COMPASS to
      promoter-proximal chromatin, which methylates histone H3 lysine 4 (H3K4) to form
      H3K4me1, H3K4me2 and H3K4me3. Here, we determine the importance of COMPASS in
      maintaining gene expression across lifespan in budding yeast. We find that
      COMPASS mutations reduce replicative lifespan and cause expression defects in
      almost 500 genes. Although H3K4 methylation is reported to act primarily in gene
      repression, particularly in yeast, repressive functions are progressively lost
      with age while hundreds of genes become dependent on H3K4me3 for full expression.
      Basal and inducible expression of these genes is also impaired in young cells
      lacking COMPASS components Swd1 or Spp1. Gene induction during ageing is
      associated with increasing promoter H3K4me3, but H3K4me3 also accumulates in non
      promoter regions and the ribosomal DNA. Our results provide clear evidence that
      H3K4me3 is required to maintain normal expression of many genes across organismal
      lifespan.

PMID- 30274597
TI  - Thy Mind, Thy Brain and Time.

PMID- 30274598
TI  - Millisecond Spike Timing Codes for Motor Control.
AB  - Millisecond variations in spiking patterns can radically alter motor behavior,
      suggesting that traditional rate-based theories of motor control require
      revision. The importance of spike timing in sensorimotor control arises from
      dynamic interactions between the nervous system, muscles, and the body. New
      mechanisms, model systems, and theories are revealing how these interactions
      shape behavior.

PMID- 30274599
TI  - Evolution of Locomotor Rhythms.
AB  - Nervous systems control locomotion using rhythmically active networks that
      orchestrate motor neuron firing patterns. Whether animals use common or distinct
      genetic programs to encode motor rhythmicity remains unclear. Cross-species
      comparisons have revealed remarkably conserved neural patterning systems but have
      also unveiled divergent circuit architectures that can generate similar locomotor
      behaviors.

PMID- 30274600
TI  - Language and the Construction of Time through Space.
AB  - Speakers of different languages think about time differently in accordance with
      the spatial metaphors common in their languages. Furthermore, learning new
      spatial metaphors in language instills new non-linguistic representations of
      time, suggesting that language can play a causal role in constructing mental
      timelines.

PMID- 30274601
TI  - Memory, Novelty and Prior Knowledge.
AB  - Over the 40 years that TINS has been in existence, there has been substantial
      progress in understanding the types, organisation, and neural mechanisms of
      memory. The selectivity of memory maintenance and retention remains a puzzle, and
      we here summarise two contributions of our own research to this enigma: the
      striking impact of the novelty and surprise often of other events happening
      around the time that a new memory is encoded and how activated prior knowledge
      guides the updating process that characterises aspects of memory consolidation.

PMID- 30274602
TI  - Hormonal Cycles, Brain Network Connectivity, and Windows of Vulnerability to
      Affective Disorder.
AB  - The rate of affective disorder is substantially higher in women than in men, and
      considerable evidence points to the actions of ovarian hormones in mediating this
      disparity. In this Opinion, we discuss the hypothesis that cyclic changes in
      ovarian hormone levels produce cyclic alterations in connectivity between the
      intrinsic networks of the brain. These alterations produce specific temporal
      windows within the menstrual cycle when internetwork connectivity is increased,
      associated with increased stress reactivity and better memory for unpleasant,
      arousing events, leading to increased negative mood and susceptibility to
      affective disorder. Our windows of vulnerability model offers insights for both
      treatment of affective disorder and research on sex differences in the brain.

PMID- 30274603
TI  - Circadian Clocks and Sleep: Impact of Rhythmic Metabolism and Waste Clearance on
      the Brain.
AB  - The rotation of the Earth around its axis causes periodic exposure of half of its
      surface to sunlight. This daily recurring event has been internalized in most
      organisms in the form of cellular circadian clock mechanisms. These cellular
      clocks are synchronized with each other in various ways to establish circadian
      networks that build the circadian program in tissues and organs, coordinating
      physiology and behavior in the entire organism. In the mammalian brain, the
      suprachiasmatic nucleus (SCN) receives light information via the retina and
      synchronizes its own neuronal clocks to the light signal. Subsequently, the SCN
      transmits this information to the network of clocks in tissues and organs,
      thereby synchronizing body physiology and behavior. Disruption of cellular clocks
      and/or destruction of the synchronization between the clocks, as experienced for
      instance in jet lag and shift-work conditions, affects normal brain function and
      can lead to metabolic problems, sleep disturbance, and accelerated neurological
      decline. In this review, we highlight ways through which the circadian system can
      coordinate normal brain function, with a focus on metabolism and metabolic
      astrocyte-neuron communications. Recent developments, for example, on how waste
      clearance in the brain could be modulated by the circadian clock, will also be
      discussed. This synthesis provides insights into the impact of metabolism not
      only on the circadian clock, but also on sleep and how this connection may
      exacerbate neurological diseases.

PMID- 30274606
TI  - When Sound Stops: Offset Responses in the Auditory System.
AB  - The auditory modality is fundamentally a temporal sense that requires analysis of
      changes in sound signals on timescales ranging from microseconds to minutes. To
      generate a faithful representation of changes in sound intensity and frequency
      over time, sound offsets (disappearances) as well as sound onsets (appearances)
      must be encoded by the auditory system. We review here the computational
      significance, perceptual roles, anatomical locations, and cellular and network
      origins of sound-offset responses in the mammalian auditory brain. We show that
      sound-offset responses arise from mechanisms and pathways distinct from those
      producing sound-onset responses, and are likely to be essential for auditory
      processing of temporally discontinuous sounds such as speech.

PMID- 30274604
TI  - Inhibitory Interneurons Regulate Temporal Precision and Correlations in Cortical
      Circuits.
AB  - GABAergic interneurons, which are highly diverse, have long been thought to
      contribute to the timing of neural activity as well as to the generation and
      shaping of brain rhythms. GABAergic activity is crucial not only for entrainment
      of oscillatory activity across a neural population, but also for precise
      regulation of the timing of action potentials and the suppression of slow
      timescale correlations. The diversity of inhibition provides the potential for
      flexible regulation of patterned activity, but also poses a challenge to
      identifying the elements of excitatory-inhibitory interactions underlying network
      engagement. This review highlights the key roles of inhibitory interneurons in
      spike correlations and brain rhythms, describes several scales on which GABAergic
      inhibition regulates timing in neural networks, and identifies potential
      consequences of inhibitory dysfunction.

PMID- 30274608
TI  - The Combinatorial Creature: Cortical Phenotypes within and across Lifetimes.
AB  - The neocortex is one of the most distinctive structures of the mammalian brain,
      yet also one of the most varied in terms of both size and organization. Multiple
      processes have contributed to this variability, including evolutionary mechanisms
      (i.e., alterations in gene sequence) that alter the size, organization, and
      connections of neocortex, and activity dependent mechanisms that can also modify
      these same features. Thus, changes to the neocortex can occur over different time
      scales, including within a single generation. This combination of genetic and
      activity dependent mechanisms that create a given cortical phenotype allows the
      mammalian neocortex to rapidly and flexibly adjust to different body and
      environmental contexts, and in humans permits culture to impact brain
      construction.

PMID- 30274607
TI  - Roles of Brain Criticality and Multiscale Oscillations in Temporal Predictions
      for Sensorimotor Processing.
AB  - Sensorimotor predictions are essential for adaptive behavior. In natural
      environments, events that demand sensorimotor predictions unfold across many
      timescales, and corresponding temporal predictions (either explicit or implicit)
      should therefore emerge in brain dynamics. Neuronal oscillations are scale
      specific processes found in several frequency bands. They underlie periodicity in
      sensorimotor processing and can represent temporal predictions via their phase
      dynamics. These processes build upon endogenous neural rhythmicity and adapt in
      response to exogenous timing demands. While much of the research on periodicity
      in neural processing has focused on subsecond oscillations, these fast-scale
      rhythms are in fact paralleled by critical-like, scale-free dynamics and
      fluctuations of brain activity at various timescales, ranging from seconds to
      hundreds of seconds. In this review, we put forth a framework positing that
      critical brain dynamics are essential for the role of neuronal oscillations in
      timing and that cross-frequency coupling flexibly organizes neuronal processing
      across multiple frequencies.

PMID- 30274609
TI  - When to Choose Surgery in the Era of Transcatheter Aortic Valve Replacement.
AB  - Treatment of severe symptomatic aortic stenosis has undergone significant changes
      with the advent of transcatheter aortic valve replacement (TAVR). Initially
      reserved for inoperable patients, these devices have improved; outcomes now rival
      or outperform surgical treatment. TAVR is recommended for high-risk and certain
      intermediate-risk patients. As transcatheter aortic valve replacement becomes an
      option for younger, healthier patients, long-term planning and thoughtful
      considerations of potential subsequent interventions are paramount. A robust
      understanding of risks, benefits and expected outcomes with TAVR is critical to
      provide patients with the best treatment option.

PMID- 30274610
TI  - Minimalist Transcatheter Aortic Valve Replacement: The Right Pathway Forward?
AB  - Minimalist transcatheter aortic valve replacement (TAVR) can be implemented with
      no apparent compromise in patient outcomes. Although this approach is applicable
      for many patients undergoing TAVR, patient selection by the heart team is
      critical; one must be cognizant of factors whereby a minimalist approach is
      unsuitable. In the current era of TAVR, a minimalist approach should encompass
      the entire process of care and not just the procedure. Streamlining and
      homogenizing preprocedural workup has potential benefits for patients and health
      services. Minimalist TAVR is likely the right pathway forward for most patients,
      but the focus should be patient centered with no compromise to safety.

PMID- 30274605
TI  - Short-Term Synaptic Plasticity as a Mechanism for Sensory Timing.
AB  - The ability to detect time intervals and temporal patterns is critical to some of
      the most fundamental computations the brain performs, including the ability to
      communicate and appraise a dynamically changing environment. Many of these
      computations take place on the scale of tens to hundreds of milliseconds.
      Electrophysiological evidence shows that some neurons respond selectively to
      duration, interval, rate, or order. Because the time constants of many time
      varying neural and synaptic properties, including short-term synaptic plasticity
      (STP), are also in the range of tens to hundreds of milliseconds, they are strong
      candidates to underlie the formation of temporally selective neurons.
      Neurophysiological studies indicate that STP is indeed one of the mechanisms that
      contributes to temporal selectivity, and computational models demonstrate that
      neurons embedded in local microcircuits exhibit temporal selectivity if their
      synapses undergo STP. Converging evidence suggests that some forms of temporal
      selectivity emerge from the dynamic changes in the balance of excitation and
      inhibition imposed by STP.

PMID- 30274611
TI  - Paravalvular Regurgitation After Transcatheter Aortic Valve Replacement: Is the
      Problem Solved?
AB  - Paravalvular regurgitation is a frequent complication after transcatheter aortic
      valve replacement and its association with worse outcomes depends on the degree
      of its severity. Despite substantial improvement in transcatheter heart valve
      design, sizing and implantation technique, moderate or severe paravalvular
      regurgitation still occurs in 2% to 7% of patients and is associated with a more
      than 2-fold increase in mortality. This review provides a state-of-the-art
      approach to (i) paravalvular regurgitation prevention by optimizing patient
      selection, valve sizing, and positioning and (ii) the detection, quantitation and
      management of paravalvular regurgitation during and after valve implantation.

PMID- 30274612
TI  - Revisiting Atrial Fibrillation in the Transcatheter Aortic Valve Replacement Era.
AB  - Atrial fibrillation (AF) is a known complication of many cardiac procedures,
      including those undergoing surgical aortic valve replacement (SAVR). In the
      transcatheter aortic valve replacement (TAVR) era, AF has been noted not only to
      be present in these patients but also associated with morbidity and mortality. In
      this article, we first outline the significance of AF in general and then more
      specifically in patients undergoing cardiac surgery. We then compare and contrast
      specific clinical issues related to AF in patients with aortic stenosis
      undergoing aortic valve replacement, traditionally with SAVR, but now
      increasingly more common with TAVR.

PMID- 30274614
TI  - Transcatheter Aortic Valve Replacement for Bicuspid Aortic Valve: Challenges and
      Pitfalls.
AB  - Because of the unfavorable anatomic features of bicuspid aortic stenosis (AS),
      the outcomes of transcatheter aortic valve replacement (TAVR) in bicuspid AS were
      suboptimal, particularly when using the first-generation transcatheter valves.
      However, the newer-generation transcatheter valves significantly improved the
      outcomes of TAVR in bicuspid AS. Nonetheless, long-term durability of
      transcatheter valves and concomitant aortopathy should be taken into account.
      Considering the expanding indication of TAVR to lower the surgical risk and a
      younger population, these issues should be evaluated in future studies.

PMID- 30274613
TI  - Coronary Artery Disease and Transcatheter Aortic Valve Replacement: When to
      Intervene.
AB  - "In patients with coronary artery disease undergoing transcatheter aortic valve
      replacement (TAVR), the decision of whether to revascularize, which lesions to
      revascularize, and the optimal timing of revascularization remains controversial.
      The sequence of revascularization should be made on a case-by-case basis. Pre
      TAVR revascularization (staged or simultaneous with TAVR) is preferred due to
      unobstructed access to coronary ostia and is important to consider especially in
      cases in which long self-expanding valves are used. In patients who are
      hemodynamically compromised, the valve should be addressed first, as the most
      important cause of mortality is heart/multiorgan failure."

PMID- 30274616
TI  - Endovascular Treatment Options for the Aortic Arch.
AB  - Endovascular aortic repair to treat aortic arch abnormality has rapidly expanded
      in the last 2 decades, and surgeons now have options to treat patients who are
      poor candidates for open surgery. The devices and techniques should be tailored
      to the extension of the aortic abnormality and anatomy of the individual. Recent
      studies demonstrate promising results with branched endografts, but one of the
      major drawbacks of the devices is that considerable time is required to prepare
      the custom-made graft, which may not be available for emergent or urgent cases.
      Introduction of commercially available devices is forthcoming.

PMID- 30274615
TI  - Innovations in Transcatheter Valve Technology: What the Next Five Years Hold.
AB  - Transcatheter aortic valve replacement is indicated for the treatment of
      symptomatic severe aortic stenosis in patients at intermediate or greater risk
      for surgery. Future indications may include low-risk patients, asymptomatic
      patients, bicuspid valves, moderate aortic stenosis, and pure native aortic valve
      regurgitation. Key hurdles to overcome include pacemaker risk, vascular injury,
      paravalvular regurgitation, coronary artery reaccess, durability, and embolic
      risk. New valve designs include synthetic polymeric valves that may allow for
      greater durability, in addition to advances in terms of precise positioning and
      repositioning to reduce the complication rate.

PMID- 30274617
TI  - Evolution of Transcatheter Valve Therapy for Aortic Stenosis.

PMID- 30274618
TI  - Type 2 diabetes and coronary artery disease: Preserved ejection fraction and
      sudden cardiac death.
AB  - BACKGROUND: Previous studies have shown that type 2 diabetes (DM2) is associated
      with sudden cardiac death (SCD) risk in post-myocardial infarction patients. The
      treatment of coronary artery disease (CAD) as well as DM2 has changed over time.
      OBJECTIVE: The purpose of this study was to compare the incidence of SCD in DM2
      and nondiabetic patients with CAD and preserved ejection fraction (EF) in a
      prospective observational study (ARTEMIS study). METHODS: In 834 DM2 patients and
      1112 nondiabetic patients with CAD enrolled, the EF measured >=3 months after
      qualifying was 63% +/- 10% in DM2 patients and 65% +/- 8% in nondiabetic patients
      (P < .01). The primary end point was SCD or resuscitation from sudden cardiac
      arrest (SCA). All-cause mortality, cardiac mortality, non-SCD, hospitalization
      for heart failure, and acute coronary syndrome were secondary end points.
      RESULTS: During a mean follow-up of 6.3 +/- 1.6 years, SCDs/SCAs occurred in 50
      patients. The prevalence of SCD/SCA was higher in DM2 patients (4.1%) than in
      nondiabetic patients (1.4%) (adjusted hazard ratio 2.6; 95% confidence interval
      1.3-5.3; P < .01). However, the non-SCD component of cardiac mortality was not
      significantly different between DM2 and nondiabetic patients. In addition, heart
      failure hospitalizations were more common in DM2 patients (8.4%) than in
      nondiabetic patients (2.9%) (P < .001). The annual cardiac mortality in
      nondiabetic patients with CAD was 0.50%, which was lower than the 0.59% reported
      in the general Finnish population. CONCLUSION: DM2 is an independent risk factor
      for SCD/SCA in CAD patients with preserved EF. Cardiac mortality in nondiabetic
      CAD patients is slightly lower than that in the general population in the present
      treatment era.

PMID- 30274619
TI  - A wobbling tachycardia: What is the mechanism?

PMID- 30274620
TI  - A 73-year-old woman with high-degree AV block.

PMID- 30274621
TI  - Renal Involvement in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
AB  - Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is the most
      common cause of rapidly progressive glomerulonephritis. ANCAs play an important
      role in the pathogenesis and diagnosis of AAV. The classic renal lesion in AAV is
      a pauci-immune necrotizing and crescentic glomerulonephritis. Treatment is
      divided into 2 phases: (1) induction of remission to eliminate disease activity
      and (2) maintenance of remission to prevent disease relapse. AAV patients with
      end-stage renal disease require modification of immunosuppressive strategies and
      consideration for kidney transplantation. An improved understanding of disease
      pathogenesis has led to new treatment strategies being tested in clinical trials.

PMID- 30274622
TI  - Therapy for Proliferative Lupus Nephritis.
AB  - Proliferative lupus nephritis requires prompt diagnosis and treatment with
      immunosuppressive therapy. Cyclophosphamide is the longest studied agent, but
      mycophenolate mofetil has recently emerged as an efficacious induction and
      maintenance treatment that does not impart the risk of infertility. However,
      overall remission rates remain suboptimal and there is a need for improved
      therapeutic options. To this end, ongoing clinical studies are focusing on agents
      that target key molecules and pathways implicated in the pathogenesis of lupus
      nephritis based on previous animal and human studies. This article reviews key
      findings of trials supporting established induction and maintenance treatment
      regimens along with novel therapeutic investigations.

PMID- 30274623
TI  - Nonproliferative Forms of Lupus Nephritis: An Overview.
AB  - Most of the attention paid to lupus nephritis, in the medical literature and in
      clinical trials, has primarily focused on proliferative forms of lupus nephritis
      (class III and IV lesions), but with lower thresholds to biopsy and rebiopsy
      patients with lupus, clinicians are encountering more cases with purely mesangial
      disease (class I and II) or membranous nephropathy patterns (class V). These
      lesions often will be associated with milder disease courses but still require
      dedicated follow-up by a nephrologist and focused therapeutic strategies that, at
      times, will include immunosuppression.

PMID- 30274625
TI  - Secondary, AA, Amyloidosis.
AB  - Secondary, AA, amyloidosis is a rare systemic complication that can develop in
      any long-term inflammatory disorder, and is characterized by the extracellular
      deposition of fibrils derived from serum amyloid A (SAA) protein. SAA is an acute
      phase reactant synthetized largely by hepatocytes under the transcriptional
      regulation of proinflammatory cytokines. The kidney is the major involved organ
      with proteinuria as first clinical manifestation; renal biopsy is the commonest
      diagnostic investigation. Targeted anti-inflammatory treatment promotes
      normalization of circulating SAA levels preventing amyloid deposition and renal
      damage. Novel therapies aimed at promoting clearance of existing amyloid deposits
      soon may be an effective treatment approach.

PMID- 30274624
TI  - Renal Manifestations of Rheumatoid Arthritis.
AB  - Renal manifestations in rheumatoid arthritis (RA) have evolved as RA management
      has improved. In the past, older disease-modifying antirheumatic drugs,
      uncontrolled systemic inflammation, and chronic nonsteroidal antiinflammatory
      drug (NSAID) use contributed to kidney disease. Over time, the use of
      methotrexate and biologic medications, decrease in NSAID use, and a treat-to
      target strategy have contributed to a decrease in renal manifestations. Chronic
      kidney disease in RA now is more likely to be caused by cardiovascular risk
      factors than uncontrolled RA disease severity. In patients with renal
      dysfunction, NSAIDs, methotrexate, and tofacitinib may need to be adjusted or
      avoided to prevent adverse events.

PMID- 30274626
TI  - Nephrotoxicity of Select Rheumatologic Drugs.
AB  - Several drugs commonly used in the management of rheumatic diseases may lead to
      nephrotoxicity, electrolyte disturbances, and hypertension. Here the authors
      focus on nonsteroidal antiinflammatory drugs, uric-acid-lowering therapy, and
      commonly used immunosuppressant therapies. The authors include a drug dosing
      table for patients with kidney disease.

PMID- 30274627
TI  - Acute and Chronic Tubulointerstitial Nephritis of Rheumatic Causes.
AB  - Tubulointerstitial nephritis (TIN) is the second most common cause of acute
      intrinsic kidney injury after acute tubular necrosis. Although drug-induced forms
      of TIN represent the vast majority, rheumatic disease is another common cause and
      often underdiagnosed. Early diagnosis of acute interstitial nephritis and prompt
      withdrawal of the culprit medication or a correct treatment can avoid chronic
      damage and progressive chronic kidney disease. This review highlights the recent
      updates, clinical features, and treatment in TIN in autoimmune rheumatic disease.

PMID- 30274628
TI  - Thrombotic Microangiopathies with Rheumatologic Involvement.
AB  - Thrombotic microangiopathies are heterogeneous disorders characterized by
      microangiopathic hemolytic anemia with thrombocytopenia and renal injury. There
      are a variety of causes, including metabolic disorders, infections, medications,
      complement disorders, pregnancy, malignancy, and autoimmune disorders. This
      review focuses on renal thrombotic microangiopathy in the setting of
      rheumatologic diseases. Systemic lupus erythematosus is the most common
      autoimmune disease associated with thrombotic microangiopathy. Other etiologies
      include scleroderma renal crisis and antiphospholipid antibody syndrome, which
      can be primary or secondary to autoimmune diseases including systemic lupus
      erythematosus. There have also been case reports of thrombotic microangiopathy in
      the setting of rheumatoid arthritis and dermatomyositis.

PMID- 30274629
TI  - Anti-Glomerular Basement Membrane Disease.
AB  - Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune small
      vessel vasculitis characterized by autoreactivity to antigens in type IV collagen
      chains expressed in glomerular and alveolar basement membrane. The detection of
      circulating anti-GBM antibodies, which are shown to be directly pathogenic, is
      central to disease diagnosis. Clinically, anti-GBM disease usually presents with
      rapidly progressive glomerulonephritis with or without alveolar hemorrhage. Rapid
      diagnosis and early treatment are required to prevent mortality and to preserve
      renal function. Relapse in anti-GBM disease is uncommon. Variant and atypical
      forms of anti-GBM disease are increasingly recognised.

PMID- 30274630
TI  - Autoimmune Kidney Diseases Associated with Chronic Viral Infections.
AB  - Autoimmune kidney diseases triggered by viruses are an important cause of kidney
      disease in patients affected by chronic viral infection. Hepatitis B virus (HBV)
      infection is associated with membranous nephropathy and polyarteritis nodosa.
      Hepatitis C virus (HCV) infection is a major cause of cryoglobulinemic
      glomerulonephritis. Patients with human immunodeficiency virus (HIV) may develop
      HIV-associated nephropathy, a form of collapsing focal segmental
      glomerulosclerosis, or various forms of immune-complex-mediated kidney diseases.
      This article summarizes what is known about the pathogenesis, diagnosis, and
      management of immune-mediated kidney diseases in adults with chronic HBV, HCV,
      and HIV infections.

PMID- 30274632
TI  - Renal Involvement in Rheumatic Diseases.

PMID- 30274631
TI  - Renal Manifestations of Inflammatory Bowel Disease.
AB  - Renal and urinary involvement has been reported to occur in 4% to 23% of
      inflammatory bowel disease (IBD) patients. Parenchymal renal disease is rare and
      most commonly affects glomerular and tubulointerstitial compartments. The most
      common findings on renal biopsy of IBD patients are IgA nephropathy and
      tubulointerstitial nephritis. Overall morbidity of IBD-related renal
      manifestations is significant, and there is often only a short window of injury
      reversibility. This, along with subtle clinical presentation, requires a high
      index of suspicion and routine monitoring of renal function. There are no
      established guidelines for the optimal screening and monitoring of renal function
      in IBD patients.

PMID- 30274633
TI  - A Three-Headed Approach to Kidney Involvement in Rheumatic Diseases.

PMID- 30274634
TI  - Reconfiguring Cardiac Rehabilitation to Achieve Panvascular Prevention: New Care
      Models for a New World.
AB  - Atherosclerotic cardiovascular disease (ASCVD) and its associated economic burden
      are increasing globally. Although cardiac rehabilitation is a vital component of
      secondary prevention with proven benefits, it is underutilized due to numerous
      barriers, especially in resource-limited settings. New care models for delivery
      of comprehensive prevention programs such as community-based, home-based, and
      "hybrid" models implementing m-health, e-health, and telemedicine need to be
      adopted. Such new care models should be offered to all patients with established
      ASCVD (coronary, cerebral, and peripheral) and additionally to those at high risk
      of developing ASCVD with multiple risk factors for panvascular prevention.

PMID- 30274635
TI  - Smoking Cessation and Cardiac Rehabilitation: A Priority!
AB  - Cardiac rehabilitation programmes afford the opportunity to enhance
      cardiovascular health and reduce the risk of subsequent cardiac events. They
      permit the management of cardiac risk factors while addressing significant
      psychosocial and vocational issues. Tobacco addiction is the most important of
      the modifiable cardiac risk factors, and smoking cessation is the most important
      secondary prevention strategy. Cessation is more likely when cessation
      pharmacotherapy is accompanied by supportive advice and strategic assistance. A
      systematic approach to the delivery of cessation services, such as the Ottawa
      Model of Smoking Cessation, greatly enhances the likelihood of success. Cardiac
      rehabilitation programmes are ideal venues for the delivery of such programmes.

PMID- 30274636
TI  - Cardiac Rehabilitation Availability and Delivery in Canada: How Does It Compare
      With Other High-Income Countries?
AB  - BACKGROUND: Canada has insufficient cardiac rehabilitation (CR) capacity, yet
      unmet need is unknown. Moreover, Canada has CR guidelines, but whether delivery
      conforms has not been characterized by province/territory. This study aimed to
      establish (1) CR volumes, capacity, and density, as well as (2) the nature of
      programs, and (3) compare these (a) by province/territory and (b) with other high
      income countries (HICs). METHODS: In this cross-sectional study, an online survey
      was administered to CR programs globally. National cardiac associations were
      engaged to facilitate program identification where available, or local champions.
      Density was computed using Canada's Chronic Disease Surveillance System ischemic
      heart disease incidence estimates. Twenty-eight HICs with CR were selected for
      comparison (N = 619 programs), and multilevel analyses performed. RESULTS: CR was
      available in 10 of 13 (76.9%) provinces (no programs in Canada's North), with 74
      of 182 programs initiating a survey (40.7% response). Program volumes (median =
      250) were greatest in Ontario, but ultimately there was only 1 CR spot per 4.55
      patients with ischemic heart disease nationally (similar in other HICs), and
      186,187 more spots are needed annually. Most programs were funded by
      government/hospital sources (n = 48, 66.7%), but in 23 (31.5%), patients paid
      some or all of program costs out-of-pocket. Guideline-indicated conditions were
      accepted in more than 90% of programs. Programs had a multidisciplinary team of
      6.2 +/- 2.1 staff, offering 7.7 +/- 1.5/10 core components (varied by province, P
      = 0.001; return-to-work offered less frequently than other HICs; P = 0.03), over
      42.0 +/- 26.0 hours (provincial and other HIC differences, P < 0.001).
      CONCLUSIONS: Canadian CR capacity must be augmented, but where available,
      services are consistent with other HICs.

PMID- 30274637
TI  - Cardiac Rehabilitation for Adults With Congenital Heart Disease: Physical and
      Psychosocial Considerations.
AB  - Owing to significant medical advances, it is now estimated that more than 90% of
      persons born with congenital heart disease (CHD) will reach adulthood. Medically
      appropriate physical activity represents an opportunity to improve physical
      functioning as well as quality of life and psychosocial outcomes. By reviewing
      published CHD research and clinical recommendations, herein we first summarize
      how adults with CHD are known to be less physically active and have reduced
      exercise capacity compared with healthy peers. Cardiopulmonary exercise testing
      is important for routine clinical management and before the onset of an exercise
      program. Physiological anomalies are common in adults with CHD, although very few
      necessitate activity restrictions, and positive results from exercise training
      have been demonstrated. In recent decades, the focus has thus shifted from
      restriction of exercise to promotion of exercise. Adults with CHD also face
      unique psychosocial challenges associated with living with a chronic cardiac
      condition, many of which may influence exercise behaviours. However, much less is
      known about participation of adults with CHD in cardiac rehabilitation (CR)
      programs, which differ from exercise training in their comprehensive,
      interdisciplinary approach to management of chronic disease and that might be
      uniquely poised to meet the physical and psychosocial needs of adults with CHD.
      Initial CR outcomes have been positive and with no reported adverse events. This
      review summarizes the unique physical and psychosocial considerations that may
      guide the provision of CR to adults with CHD.

PMID- 30274638
TI  - The Delivery of Cardiac Rehabilitation Using Communications Technologies: The
      "Virtual" Cardiac Rehabilitation Program.
AB  - Cardiac rehabilitation (CR) programs are a proven therapy for patients with
      cardiovascular disease, reducing future cardiac events and premature mortality.
      However, as little as 10% of eligible patients attend these programs, with a key
      reason being geographical inaccessibility. In Canada, more than 90% of Canadians
      have Internet access, and there are approximately 31 million cell phone
      subscribers, with these numbers expected to continue to increase. The
      proliferation of these affordable communications technologies has opened up
      opportunities for patient communication while bridging geographic distance. This
      has led to the development of "virtual" CR that can be remotely conducted,
      reaching patients in their homes and communities. These programs have used a
      range of technologies such as telephone, Internet, text messaging, and
      smartphones. Early research has focused on acceptance of use and feasibility in
      pilot studies, indicating patient willingness for use. More recently, a number of
      small, randomized trials have been conducted indicating potential positive effect
      on various clinical outcomes. This narrative review highlights the evidence to
      date on the use of virtual CR, using a variety of affordable communications
      technologies from early feasibility studies to modest randomized controlled
      trials. Finally, lessons from previous studies are discussed to help inform the
      development and testing of future virtual CR. This will be important if virtual
      CR is to become part of standard health care.

PMID- 30274639
TI  - The Effects of Cardiac Rehabilitation in Patients With Atrial Fibrillation: A
      Systematic Review.
AB  - BACKGROUND: Atrial fibrillation (AF), the most common sustained cardiac
      arrhythmia, is associated with substantial morbidity and mortality. Clinical
      guidelines for managing patients with AF do not include a referral to cardiac
      rehabilitation (CR) at present, although it is routine for most other
      cardiovascular conditions. The number of studies evaluating the impact of CR on
      the health of patients with AF is growing, but there has been no consolidation of
      the findings. The objective of this systematic review was to evaluate the impact
      of CR programs on physical and mental health outcomes in patients with all forms
      of AF. METHODS: Six electronic databases were searched to identify all studies
      that reported on the impact of CR in patients with AF. Searching identified 5771
      potential articles, of which 12 were included. The physical health outcomes
      evaluated included cardiometabolic health indicators, aerobic and functional
      capacity, severity of symptoms, recurrence of AF, hospitalizations, and
      mortality. The mental health outcomes assessed included quality of life, anxiety,
      depression, and quality of sleep. RESULTS: The limited evidence supports the use
      of CR to improve cardiometabolic health indicators and aerobic and functional
      capacity in patients with AF. The current evidence suggests that prominent
      improvements in aerobic fitness are associated with lower risk of hospitalization
      and mortality. The conflicting mental health findings may be due to the varying
      severity of AF and or modes of exercise interventions. CONCLUSIONS: Gaps in the
      research identified the need for greater rigor in the reporting of intervention
      details, outcomes, and statistical methodology; sex- and gender-based analyses;
      and effectiveness trials. This review serves as a call to action for more work
      globally on this important area.

PMID- 30274640
TI  - Investigating the effect of treatment at high-volume hospitals on overall
      survival following cytoreductive nephrectomy.
AB  - PURPOSE: Data revealed the benefit of high-volume care in many complex disease
      processes. Among patients undergoing nephrectomy, those receiving cytoreductive
      nephrectomy (CN) for metastatic renal cell cancer (mRCC) constitute a unique
      subset. They often have a greater medical and surgical complexity. Against this
      backdrop, we sought to investigate the effect of hospital volume on overall
      survival among patients undergoing CN for mRCC. MATERIAL AND METHODS: We
      identified 11,089 patients who received CN for mRCC in the National Cancer
      Database from 1998 to 2012. We ranked hospitals based on annual CN volume.
      Patients who received surgery in hospitals in the top vs. bottom deciles were
      compared. Inverse Probability of Treatment Weighting (IPTW)-adjusted Kaplan-Meier
      and Cox regression analyses were used to compare the primary endpoint of overall
      survival between balanced cohorts of patients. Secondary endpoints were 30-day
      mortality, 30-day readmissions, and receipt of subsequent systemic therapy.
      RESULTS: Median follow-up was 60.39 months (interquartile range [IQR] 35.09
      95.95). Median overall survival was 17.61 months (IQR 7.16-44.58). Following
      propensity score weighting, surgery at a high-volume hospital was associated with
      a decreased risk of mortality (IPTW-adjusted Cox proportional Hazard Ratio =
      0.91; 95% confidence interval: 0.86-0.96). On our IPTW-adjusted Kaplan-Meier
      analysis, the median survival was 19.94 months (IQR 7.98-50.27) at high-volume
      hospitals vs. 15.97 months (IQR 6.6-41.56) at low-volume hospitals. With regard
      to secondary endpoints, the data did not reveal a significant advantage for
      treatment at a high-volume hospital. CONCLUSION: We found a significant
      association between receipt of CN at high-volume hospitals and prolonged overall
      survival, demonstrated by a nearly 4 month survival benefit.

PMID- 30274641
TI  - Prognostic factors of oncologic outcomes in metastatic chemotherapy-naive
      castration-resistant prostate cancer treated with enzalutamide in actual clinical
      practice in East Asia.
AB  - OBJECTIVES: We aimed to evaluate the prognostic factors for chemotherapy-naive
      castration-resistant prostate cancer (CRPC) treated with enzalutamide in actual
      clinical practice using easily accessible clinical variables. METHODS AND
      MATERIALS: We retrospectively reviewed the following data from 113 patients with
      chemotherapy-naive CRPC treated with enzalutamide: serum levels of prostate
      specific antigen (PSA), testosterone, hemoglobin, total protein, albumin, and
      alkaline phosphatase (ALP); platelet, neutrophil, and lymphocyte counts;
      neutrophil-to-lymphocyte ratios (NLRs); and liver profiles. PSA progression-free
      survival (PFS), radiological PFS, and overall survival were estimated by Cox
      regression analysis. RESULTS: Compared with baseline levels, laboratory values at
      2 months showed significantly lower PSA (160.2 +/- 351.5 ng/ml vs. 47.4 +/- 117.1
      ng/ml) and ALP levels (201.86 +/- 223.77 IU/l vs. 148.25 +/- 146.81 IU/l) and a
      significantly higher percentage of lymphocytes (28.1% +/- 10.6% vs. 31.2% +/-
      9.7%); those at 1 month showed a significantly lower percentage of neutrophils
      (61.0% +/- 11.0% vs. 57.1% +/- 12.5%). In the multivariate analysis, poor
      prognostic factors for PSA PFS were Gleason score >= 9 (hazard ratio [HR] 2.022;
      P = 0.0250); visceral metastasis (HR 3.143; P = 0.0002); high NLR (HR 1.205; P =
      0.0126); and high ALP (HR 1.002; P = 0.0015). For radiological PFS, high NLR (HR
      1.249; P = 0.0002) and high ALP (HR 1.002; P = 0.0001) were associated with poor
      outcomes. The predictors of poor overall survival were visceral metastasis (HR
      3.155; P < 0.0001); high NLR (HR 1.341; P < 0.0001); and high ALP (HR 1.001; P =
      0.0017). CONCLUSION: Enzalutamide is less effective in patients with metastatic
      chemotherapy-naive CRPC with Gleason scores >= 9, visceral metastasis, high NLR,
      and high ALP.

PMID- 30274642
TI  - Think, Ask, Act: The Intersectionality of Mental and Reproductive Health for
      Judicially Involved Girls.
AB  - Danielle Smith, a 16-year-old African-American girl newly detained at juvenile
      hall, presents for psychiatric evaluation. She describes a history of sexual
      abuse by her foster father and 2 years of commercial sexual exploitation after
      running away at 14 years of age. Scarcely more than 100 pounds, she endorses drug
      use, primarily marijuana, and notes prior use of cocaine and methamphetamine,
      provided by her trafficker (described as her "boyfriend"). She has a timid smile
      and uses music and journaling as her refuge. Danielle is unclear about past
      psychiatric diagnoses but does recall receiving medication from a psychiatrist
      while in foster care and expresses interest in resuming treatment. Girls in the
      juvenile justice system are a vulnerable population with overlapping substance
      use, reproductive, and mental health care needs. The conceptual framework of
      "intersectionality" is useful to better understand the multiplicity of
      biopsychosocial needs of girls involved in the justice system. Intersectionality
      is defined as "a theoretical framework for understanding how multiple social
      identities (ie, race, gender, and sexual orientation) intersect at the micro
      level of individual experience to reflect systems of oppression (ie, racism,
      sexism, classism) at the macro level."1 In this article, we propose the pragmatic
      application of the concept of intersectionality to better conceptualize the high
      unmet health needs of these youth. We conclude by providing recommendations for
      meeting their needs using the proposed "think, ask, act" approach.

PMID- 30274643
TI  - What's in a Name? Moving to Neuroscience-Based Nomenclature in Pediatric
      Psychopharmacology.
AB  - Our traditional names for psychotropic medication classes lead to unnecessary
      confusion. As clinicians, we have grown comfortable with idiosyncratic names of
      psychotropic medications and have forgotten how unclear and misleading they can
      be. For example, evidence shows that serotonin reuptake inhibitors help in
      pediatric anxiety disorders, but a parent with an anxious child might ask, "If
      you diagnosed my son with separation anxiety, why are you giving him an
      antidepressant?" Another parent might object to the use of a "stimulant"
      medication, "My daughter never slows down, the last thing she needs is a
      stimulant!" Similarly, an "antipsychotic" can be prescribed on-label to youth
      with mania, bipolar depression, tics, or irritability in autism but families and
      patients might be confused by or object to the implied label of being
      "psychotic." Furthermore, patients or family members may not feel comfortable
      asking clarifying questions and simply do not return for follow up-concluding
      that the provider does not understand their child.

PMID- 30274644
TI  - Meeting the Workforce Shortage: Toward 4-Year Board Certification in Child and
      Adolescent Psychiatry.
AB  - Child Psychiatry has long been recognized as the medical specialty with the
      greatest workforce shortage.1 This shortage is of increasing concern because of
      the high burden of child and adolescent mental illness that is exemplified by the
      increasing rates of suicide in youth.

PMID- 30274645
TI  - A Risk Calculator for Bipolar Disorder in Youth: Improving the Odds for
      Personalized Prevention and Early Intervention?
AB  - There have been many longitudinal studies examining biological and environmental
      risk factors for developing bipolar disorder in youth. Specifically, well
      established risk factors for bipolar disorder in children and adolescents include
      having a family history of bipolar disorder, depression, disruptive behavior
      disorders, psychosis, antidepressant-induced manic symptoms, anxiety, and
      subsyndromal symptoms of mania and depression.1 In an effort to identify
      individuals at highest risk for developing bipolar disorder, several
      investigators have attempted to characterize a bipolar prodrome. A recent meta
      analysis of early manifestations of bipolar disorder in youth found that the most
      common prodromal symptoms were increased energy, diminished ability to think,
      indecision, pressured speech, talkativeness, elated mood, academic or work
      difficulties, insomnia, depressed mood, and increased goal-directed activities.2
      The authors concluded that despite many of the participants having symptoms prior
      to their illness onset, there was significant heterogeneity in symptom
      presentation, making it difficult to define a consistent bipolar prodrome.
      Although it is important to explore risk factors and rates of early symptoms of
      incipient bipolar disorder, to date, most studies have examined risk within an
      entire group rather than quantified an individual's risk of having bipolar
      disorder, which is essential to advance personalized monitoring and treatment
      strategies.

PMID- 30274646
TI  - Brain Markers of Familial Risk for Depression: Steps Toward Clinical Relevance?
AB  - An important goal in the field of psychiatry is to identify individuals at risk
      for major psychopathology, prior to actual onset of disorder. Discovery of risk
      markers that predict onset of disorder, if they are sensitive and specific, could
      help in the process of early diagnosis, and ultimately lead to improved early
      intervention and prevention. This is especially a key aspiration for disorders
      that take a tremendous toll on health and functioning in both adolescence and
      adulthood, including depression, bipolar disorder, and schizophrenia.

PMID- 30274647
TI  - Youth Suicide: The First Suicide Attempt.
AB  - A mainstay in the identification and management of youth at risk for suicide is
      the use of suicide risk factors, such as past suicide attempt(s), past or current
      suicidal ideation, mood disorders, substance use disorders, psychosis, male
      gender, and lack of family support.1 A history of at least 1 medically serious
      suicide attempt2 or violent self-harm3 is a particularly important risk factor.
      This phenomenon has been studied mostly with clinical samples, such as cohorts of
      patients initially admitted to a hospital for an attempt, having used a
      particular self-harm method, or seen in an emergency department.4 Olfson et al.3
      used Medicaid claims data and tracked patients for 1 year after an episode of
      self-harm. However, these studies could not contextualize completed suicides that
      were not preceded by an attempt or other self-harm. McKean et al.,5 in this issue
      of JAACAP, used a community sample to identify a cohort followed from the first
      suicide attempt that came to medical attention to the index attempt (IA),
      including an IA resulting in death. This approach facilitated an analysis that
      included individuals who lived after or died from the IA, receipt of care,
      subsequent suicide completion, method of IA and completed suicides, and
      individuals' demographic and clinical characteristics.

PMID- 30274648
TI  - Prevalence and Characteristics of Self-Harm in Adolescents: Meta-Analyses of
      Community-Based Studies 1990-2015.
AB  - OBJECTIVE: To provide meta-analytic estimates of self-harm from all community
      based studies of adolescents from 1990 through 2015, estimates of suicidal risk,
      and characteristics including age profile, frequency, types, seeking help, and
      reasons. METHOD: Databases, bibliographies, and the internet were searched for
      cross-sectional and cohort studies of 12- to 18-year-olds. Meta-analytic
      estimates of the prevalence and characteristics of self-harm, risk of suicidal
      behaviors, and rates comparing different methods were calculated. RESULTS: One
      hundred seventy-two datasets reporting self-harm in 597,548 participants from 41
      countries were included. Overall lifetime prevalence was 16.9% (95% CI 15.1
      18.9), with rates increasing to 2015. Girls were more likely to self-harm (risk
      ratio 1.72, 95% CI 1.57-1.88). The mean age of starting self-harm was 13 years,
      with 47% reporting only 1 or 2 episodes and cutting being the most common type
      (45%). The most frequent reason was relief from thoughts or feelings. Slightly
      more than half sought help, but for most this was from a friend. Suicidal
      ideation (risk ratio 4.97) and attempts (risk ratio 9.14) were significantly
      higher in adolescents who self-harmed, but this was higher with more frequent
      self-harm. Methodologic factors also were associated with higher rates of self
      harm. CONCLUSION: Interventions that can lower suicidal risk should be made
      available to adolescents who self-harm frequently as soon as possible.
      Preventative interventions that help adolescents deal with negative feelings
      should be instituted at the onset of puberty. Because friends are frequently
      asked for support, interventions also should be developed for peer groups.

PMID- 30274649
TI  - Modifying the Impact of Eveningness Chronotype ("Night-Owls") in Youth: A
      Randomized Controlled Trial.
AB  - OBJECTIVE: To determine whether an intervention to reduce eveningness chronotype
      improves sleep, circadian, and health (emotional, cognitive, behavioral, social,
      physical) outcomes. METHOD: Youth aged 10 to 18 years with an evening chronotype
      and who were "at risk" in 1 of 5 health domains were randomized to: (a)
      Transdiagnostic Sleep and Circadian Intervention for Youth (TranS-C; n = 89) or
      (b) Psychoeducation (PE; n = 87) at a university-based clinic. Treatments were 6
      individual, weekly 50-minute sessions during the school year. TranS-C addresses
      sleep and circadian problems experienced by youth by integrating evidence-based
      treatments derived from basic research. PE provides education on the
      interrelationship between sleep, stress, diet, and health. RESULTS: Relative to
      PE, TranS-C was not associated with greater pre-post change for total sleep time
      (TST) or bed time (BT) on weeknights but was associated with greater reduction in
      evening circadian preference (pre-post increase of 3.89 points, 95% CI = 2.94
      4.85, for TranS-C, and 2.01 points, 95% CI = 1.05-2.97 for PE, p = 0.006),
      earlier endogenous circadian phase, less weeknight-weekend discrepancy in TST and
      wakeup time, less daytime sleepiness, and better self-reported sleep via youth
      and parent report. In terms of functioning in the five health domains, relative
      to PE, TranS-C was not associated with greater pre-post change on the primary
      outcome. However, there were significant interactions favoring TranS-C on the
      Parent-Reported Composite Risk Scores for cognitive health. CONCLUSION: For at
      risk youth, the evidence supports the use of TranS-C over PE for improving sleep
      and circadian functioning, and improving health on selected outcomes. CLINICAL
      TRIAL REGISTRATION INFORMATION: Triple Vulnerability? Circadian Tendency, Sleep
      Deprivation and Adolescence. https://clinicaltrials.gov; NCT01828320.

PMID- 30274650
TI  - A Risk Calculator to Predict the Individual Risk of Conversion From Subthreshold
      Bipolar Symptoms to Bipolar Disorder I or II in Youth.
AB  - OBJECTIVE: Youth with subthreshold mania are at increased risk of conversion to
      bipolar disorder (BP) I/II. Predictors for conversion have been published for the
      group as a whole. However, risk factors are heterogeneous, indicating the need
      for personalized risk assessment. METHOD: One hundred forty youth with BP not
      otherwise specified (BP-NOS; 6-17 years old) followed through the Course and
      Outcome of Bipolar Youth (COBY) study with at least 1 follow-up assessment before
      conversion to BP-I/II were included. Youths were assessed on average every 7
      months (median 11.5 years) using standard instruments. Risk predictors reported
      in the literature were used to build a 5-year risk calculator. Discrimination was
      measured using the time-dependent area under the curve after 1,000 bootstrap
      resamples. Calibration was evaluated by comparing observed with predicted
      probability of conversion. External validation was performed using an independent
      sample of 58 youths with BP-NOS recruited from the Pittsburgh Bipolar Offspring
      Study. RESULTS: Seventy-five (53.6%) COBY youths with BP-NOS converted to BP
      I/II, of which 57 (76.0%) converted within 5 years. Earlier-onset BP-NOS,
      familial hypomania/mania, and high mania, anxiety, and mood lability symptoms
      were important predictors of conversion. The calculator showed excellent
      consistency between the predicted and observed risks of conversion, good
      discrimination between converters and non-converters (area under the curve 0.71,
      CI 0.67-0.74), and a proportionally increasing rate of converters at each
      successive risk class. Discrimination in the external validation sample was good
      (area under the curve 0.75). CONCLUSION: If replicated, the risk calculator would
      provide a useful tool to predict personalized risk of conversion from
      subsyndromal mania to BP-I/II and inform individualized interventions and
      research.

PMID- 30274652
TI  - Limbic Intrinsic Connectivity in Depressed and High-Risk Youth.
AB  - OBJECTIVE: Depression runs in families and has been associated with dysfunctional
      limbic connectivity. Whether aberrant limbic connectivity is a risk factor for or
      a consequence of depression is unclear. To examine this question, we compared
      resting state functional connectivity (RSFC) in youth with depressive disorders
      (DEP), healthy offspring of parents with depression (DEP-risk), and healthy
      comparison (HC) youth. METHOD: Magnetic resonance imaging at rest was acquired
      from 119 youth, aged 8 to 17 years (DEP, n = 41, DEP-risk, n = 39, and HC, n =
      39) and analyzed using seed-based RSFC in bilateral amygdala and nucleus
      accumbens (NAcc), covarying for age, IQ, and sex. RESULTS: We found distinct risk
      and disorder-specific patterns of RSFC across groups. DEP-risk and DEP youth
      shared reduced negative amygdala-right frontal cortex RSFC and reduced positive
      amygdala-lingual gyrus RSFC compared to HC youth (p < .001). DEP-risk youth had
      weaker negative amygdala-precuneus RSFC compared to DEP and HC youth (p < .001),
      suggesting a resilience marker for depression. In contrast, DEP youth had
      increased positive NAcc-left frontal cortex RSFC and reduced positive NAcc-insula
      RSFC compared to DEP-risk and HC youth (p < .001), suggestive of disorder
      specific features of depression. Greater depression severity was correlated with
      disorder-specific amygdala and NAcc RSFC (p < .05). CONCLUSION: RSFC in the
      amygdala and NAcc may represent selective disorder- and risk-specific markers in
      youth with, and at familial risk for, depression. Longitudinal studies are needed
      to determine whether these patterns predict long-term clinical outcomes.

PMID- 30274653
TI  - Rethinking Lethality in Youth Suicide Attempts: First Suicide Attempt Outcomes in
      Youth Ages 10 to 24.
AB  - OBJECTIVE: Although suicide is the second most frequent cause of death in
      American youth, suicide research has heretofore been confined to convenience
      samples that represent neither psychiatric nor general populations and that fail
      to include individuals dying at their first attempts. These limitations were
      addressed by assembling a youth cohort followed from the first medically recorded
      attempt (index attempt [IA]). It was hypothesized this approach would more
      accurately represent the prevalence of completed suicide after an attempt and
      underscore lethality based on method. METHOD: This study draws from a previously
      reported retrospective-prospective all-age cohort identified through the
      Rochester Epidemiology Project. The original 1,490-subject sample included 813
      Olmsted County youth 10 to 24 years old (n = 258 male, n = 555 female; 54.6% of
      total cohort) with IAs from January 1, 1986 through December 31, 2007 and
      followed until December 31, 2010. RESULTS: Twenty-nine of 813 subjects (3.6%)
      killed themselves during the study period, with 28 of 29 dying before their 25th
      birthday and 20 of 28 (71.4%) dying at their first attempt. Despite composing
      only 31.7% of the cohort (258 of 813), male subjects composed most suicides: 23
      of 29 (79.3% of suicides; 8.9% of male subjects) versus 6 of 29 female subjects
      (20.7% of suicides; 1.1% of female subjects). Eighty-five percent of all IA
      deaths involved firearms. More than a third of youth-41.2%-lacked a psychiatric
      history prior to IA. CONCLUSION: These data show that more than half the IAs
      occurred in youth, with approximately three-fourths of completed youth suicides
      occurring at the IAs. In parsing cause of IA death in the all-age cohort, the
      contribution of firearms figured even more prominently in the subsample of youth
      (85.0%) than in those at least 25 years old (64.3%). The high IA lethality
      suggests that prevention efforts commencing after the IA are too late for most
      victims.

PMID- 30274651
TI  - Atypical Functional Connectivity of Amygdala Related to Reduced Symptom Severity
      in Children With Autism.
AB  - OBJECTIVE: Converging evidence indicates that brain abnormalities in autism
      spectrum disorders (ASDs) involve atypical network connectivity. Given the
      central role of social deficits in the ASD phenotype, this investigation examined
      functional connectivity of the amygdala-a brain structure critically involved in
      processing of social information-in children and adolescents with ASDs, as well
      as age-dependent changes and links with clinical symptoms. METHOD: Resting-state
      functional magnetic resonance imaging (rs-fMRI) data from 55 participants with
      ASDs and 50 typically developing (TD) controls, aged 7 to 17 years, were
      included. Groups were matched for age, gender, IQ, and head motion. Functional
      connectivity MRI (fcMRI) analysis was applied to examine intrinsic functional
      connectivity (iFC) of the amygdala, including cross-sectional tests of age
      related changes. RESULTS: Direct between-group comparisons revealed reduced
      functional connectivity between bilateral amygdalae and left inferior occipital
      cortex, accompanied by greater connectivity between right amygdala and right
      sensorimotor cortex in the ASD group. This atypical pattern of amygdala
      connectivity was associated with decreased symptom severity and better overall
      functioning, as specifically seen in an ASD subgroup with the most atypical
      amygdala iFC but the least impaired social functioning. Age-related strengthening
      of amygdala-prefrontal connectivity, as observed in the TD group, was not
      detected in children with ASDs. CONCLUSION: Findings support aberrant network
      sculpting in ASDs, specifically atypical integration between amygdala and primary
      sensorimotor circuits. Paradoxical links between atypical iFC and behavioral
      measures suggest that abnormal amygdala functional connections may be
      compensatory in some individuals with ASDs.

PMID- 30274654
TI  - Mobility for All?
AB  - Substantial numbers of children and adolescents are treated with second
      generation antipsychotic medications (SGAs), and the cardiometabolic adverse
      effects of this medication class have raised concerns.1 In the October 2017 issue
      of the Journal, Handen et al.2 published a 16-week open-label extension study of
      youth 6 to 17 years of age with autism spectrum disorder treated with liquid
      metformin after a 16-week double-blinded, placebo-controlled clinical efficacy
      trial. The acute-phase and open-label extension trials demonstrated that liquid
      metformin was well tolerated, and significant improvements in body mass index z
      scores were observed in the metformin-metformin and placebo-metformin groups.2
      Handen et al.2 concluded that metformin can be effective for decreasing weight
      gain associated with SGA use and maintaining prior improvement in children and
      adolescents with autism spectrum disorder.

PMID- 30274655
TI  - Dr. Handen et al. Reply.
AB  - We thank Dr. Higdon et al. for their interest in our article on metformin and
      children with autism spectrum disorders (ASD) and for providing information about
      the MOBILITY study (a Patient-Centered Outcomes Research Institute (PCORI)-funded
      pragmatic clinical trial to examine the relative effectiveness of metformin plus
      healthy lifestyle instruction versus healthy lifestyle instruction alone).1 In
      our October 2017 article,2 we reported the results of a 16-week open-label
      extension study of a group of 61 children and adolescents with ASD prescribed
      second-generation antipsychotic medications (SGAs) who previously participated in
      a randomized controlled trial (RCT) of metformin for management of weight gain.
      Although Higdon et al. indicated that our study results were encouraging, they
      believed that the conclusion of the accompanying JAACAP editorial3 stating
      metformin be considered as an adjunct treatment for any child who is overweight
      and prescribed SGAs was premature. Instead, they recommended that the results of
      their current pragmatic trial for children with bipolar disorder (which includes
      some children with ASD and intellectual disability) would better provide
      information on relevant moderators and mediators of metformin's effects. Such
      information would be of use to clinicians in determining whether to prescribe
      metformin to their patients or to focus on lifestyle changes (or a combination of
      the 2).

PMID- 30274656
TI  - Drs. Walkup and Cottingham Reply.
AB  - Thank you to the authors for taking the time to read our editorial "Antipsychotic
      Induced Weight Gain and Metformin"1 in JAACAP and send in a letter to the editor
      with comments.

PMID- 30274657
TI  - Antenatal Depression, Epigenetic Gestational Age, Childhood Psychiatric Symptoms,
      and the Need to Consider the Possible Effects of Unaccounted Confounders.
AB  - Suarez et al.1 examined associations among antenatal depression, epigenetic
      gestational age (EGA) as a novel biomarker, and early childhood psychiatric
      problems. They found that greater severity of antenatal depression predicted
      lower EGA and that lower EGA predicted total and internalizing problems at 3.7
      years of age. Although they included many covariates in their analysis, we
      believe that the value of the study could have been enhanced by the inclusion of
      potentially important but unaddressed confounders.

PMID- 30274658
TI  - Dr. Lahti-Pulkkinen et al. Reply.
AB  - In their Letter to the Editor, "Antenatal Depression, Epigenetic Gestational Age,
      Childhood Psychiatric Symptoms, and the Need to Consider the Possible Effects of
      Unaccounted Confounders," Ghosh et al.1 suggested that unaccounted confounders
      might explain the associations of child epigenetic gestational age at birth with
      maternal antenatal depression and child psychiatric problems reported in the
      article by Suarez et al., "The Epigenetic Clock at Birth: Associations With
      Maternal Antenatal Depression and Child Psychiatric Problems."2 Although the
      covariates mentioned in the letter, namely maternal substance use during
      pregnancy and socioeconomic circumstances, are indeed important factors possibly
      affecting both maternal and child psychopathology risk, we did not adjust for
      them in our analyses, as they were not associated with child epigenetic
      gestational age in our study sample.

PMID- 30274659
TI  - Blown Away.
AB  - This month's Book Forum caught me by surprise. Although I enjoyed reading Carrie
      Cariello's What Color Is Monday and learned so much about legal and financial
      issues families have to consider in Caring for Autism, I never expected my
      response to our featured film, Keep the Change.

PMID- 30274660
TI  - Union of the medial clavicular epiphysis in a South African Black skeletal
      sample.
AB  - Current research points to an increase in the interest in and focus on the age at
      which the medial end of the clavicle begins and completes union in various
      populations worldwide. As it currently stands, no information exists for the
      South African population detailing the age at which this skeletal developmental
      marker commences or completes union. The aim of this study was to establish the
      age at which partial and complete unions occur and to find if there is any
      correlation between the age and the assigned stage score in a South African Black
      skeletal sample. Paired clavicles of 211 males and females (M = 101, F = 110)
      with ages ranging between 12 and 45 years from the Raymond A. Dart Collection of
      Human Skeletons were included. A strong correlation between age and the assigned
      stage score was observed for both males and females (rs = 0.73). No statistically
      significant differences between the stage of union at the left and right
      clavicles were observed (p = 0.9). In this sample, partial union was commonly
      observed in individuals in their third decade of life; while complete union
      occurred more often in individuals older than 30 years of age. Assessing and
      recording the degree of union at the medial end of the clavicle can be a helpful
      additional age-at-death indicator to use when establishing an age-at-death range.
      However, overlap and variability between the ages of individuals categorized as
      either displaying signs of partial or complete union were evident.

PMID- 30274661
TI  - A novel method for the prediction of focal wavefront origins in cardiac
      arrhythmias.
AB  - BACKGROUND: Current techniques for mapping and ablating cardiac arrhythmias are
      valuable, but have limitations. We devised a novel method of predicting the
      origin of a focal arrhythmia wavefront that utilizes conduction velocity (CV),
      the difference in electrogram timing during arrhythmia (t), and the distance
      between two points (z) to generate prediction curves which can be applied to an
      electroanatomic map. The intersection of two such curves predicts the origin of
      the wavefront. OBJECTIVE: To describe the rationale behind a novel method of
      arrhythmia mapping and assess its feasibility in a retrospective study of focal
      arrhythmias. METHODS: We retrospectively studied 12 patients with arrhythmias
      with focal chamber activation that were successfully mapped and treated with
      ablation. CV during arrhythmia was measured using electroanatomic mapping
      software. Values for z and t were calculated for two pairs of points. Two
      prediction curves were generated and superimposed onto the electroanatomic maps.
      The distance between the intersection of the two curves and the wavefront origin
      was recorded. The shortest distance between individual curves and the wavefront
      origin was also measured. RESULTS: Twenty-four curves were successfully generated
      in 12 patients. The distance from the intersection of two curves and the
      wavefront origin was 9.2 +/- 7.7 mm. The shortest distance between individual
      prediction curves and the wavefront origin was 5.2 +/- 5.2 mm. CONCLUSIONS:
      Wavefront origins may be predicted by a novel method utilizing a limited number
      of measurements. Further study of this method requires its integration with an
      electroanatomical mapping system.

PMID- 30274662
TI  - Robust Hinfinity control for networked control systems with randomly occurring
      uncertainties: Observer-based case.
AB  - This paper investigates the problem of observer-based robust Hinfinity output
      feedback control for networked control systems (NCSs) with randomly occurring
      uncertainties, dynamic quantization, and packet loss. It is assumed that the
      system measurement output will be quantized by a dynamic quantizer and the random
      packet loss is represented by Bernoulli random binary distribution. In the
      presence of randomly occurring uncertainties, dynamic quantization, and packet
      loss, the attention of this research is focused on the design of observer-based
      robust Hinfinity output feedback controller such that the resulting system is
      stochastically stable with the prescribed Hinfinity noise attenuation level. The
      sufficient condition for the existence of such output feedback controller is
      expressed in the form of linear matrix inequality (LMI). Simulation results of
      two illustrative examples are proposed to demonstrate the effectiveness of the
      developed design method.

PMID- 30274663
TI  - Analytical criterion on stabilization of fractional-order plants with interval
      uncertainties using fractional-order PDMU controllers with a filter.
AB  - This paper proposes a stabilization criterion for a fractional-order plant
      involving interval uncertainties in the coefficients using fractional-order PDMU
      controller with a filter. The vertex functions of the value set corresponding to
      the characteristic function of the closed loop system are determined by the law
      of Minkowski sum. The finite test frequency interval is offered to simplify the
      calculation of the test for the stabilization. The analytical method to test the
      position relationship between the origin and the value set is investigated within
      the finite test frequency interval. Then, the stabilization criterion with an
      analytical method is provided based on the zero exclusion principle. Finally,
      three examples are given to verify the effectiveness of this criterion.

PMID- 30274665
TI  - The Relationship Between Personality Characteristics, Tenure, and Intent to Leave
      Among Emergency Nurses.
AB  - INTRODUCTION: Emergency nursing turnover rates are high in the United States.
      Little is known about the role of personality characteristics in the turnover
      decisions of emergency nurses. Intent to leave is often measured to determine the
      likelihood of turnover versus retention of employees. The aim of this study is to
      examine the relationship among personality characteristics, employment tenure,
      and intent to leave among emergency nurses. METHODS: Using a descriptive,
      correlational design, data were collected using the HEXACO-PI-R personality
      inventory and demographic data. Participants included 406 current and former
      emergency nurses with employment tenure ranging from < 1 year to > 10 years.
      RESULTS: Analysis indicated a significant relationship between years of tenure
      and the traits of Honesty/Humility (P = 0.003), Emotionality (P = 0.001),
      Agreeableness (P = 0.02), and Openness (P = 0.05). When factoring in intent to
      leave, nurses with tenure longer than 10 years have significantly higher levels
      of Honesty/Humility (P = 0.001) and a significantly lower level of Emotionality
      (P = 0.011) than nurses with tenure of less than 2 years and intent to leave
      within 1 year. Finally, all 406 emergency nurses in this dataset had similarity
      among the 6 measured personality dimensions. DISCUSSION: This study found
      similarities in personality characteristics for all 406 study participants, with
      significant differences related to career tenure for some dimensions. This type
      of knowledge might provide administrators with details of important
      characteristics to foster which may have a positive impact on retention.

PMID- 30274666
TI  - Management of Opioid Overdose Victims Outside the Emergency Department: A Case
      Discussion.

PMID- 30274667
TI  - Hide and seek: Directing top-down attention is not sufficient for accelerating
      conscious access.
AB  - At any moment in time, we have a single conscious visual experience representing
      a minute part of our visual world. As such, the visual input stimulating our
      retinae is in continuous competition for reaching conscious access. Many complex
      cognitive operations can only be applied to consciously accessible visual
      information, thereby raising the question whether humans have the ability to
      select which parts of their visual input reaches consciousness. Top-down
      attention allows humans to flexibly assign more processing resources to certain
      parts of our visual input, making it a likely mechanism to volitionally bias
      conscious access. Here, we investigated whether directing top-down attention to a
      particular location or feature accelerates conscious access of an initially
      suppressed visual stimulus at the attended location, or of the attended feature.
      We instructed participants to attend a spatial location (Experiment 1) or color
      (Experiment 2) for a speeded discrimination task, using a highly predictive cue.
      The predictive cues were highly effective in prompting sustained attention
      towards the cued location or color, as evidenced by faster discrimination of cued
      relative to uncued targets. We simultaneously measured detection times to
      interocularly suppressed probes that were either of the cued (i.e., attended)
      color/location or not, and were visually distinct from the targets used for the
      discrimination task. Despite our successful manipulation of top-down attention,
      suppressed probes were not released from suppression faster when they were
      presented at the attended location, or in the attended color. In contrast, when
      observers were cued to attend a color for locating targets of an ill-defined
      shape (inciting a broader attentional template), we did observe faster conscious
      access of probes in the attended color (Experiment 3). We discuss our findings in
      light of the specificity of attentional templates, and the inherent limitations
      that this poses for top-down attentional biases on conscious access.

PMID- 30274668
TI  - The measurement of episodic foresight: A systematic review of assessment
      instruments.
AB  - Prospection, or thinking about the future, is currently a topic of significant
      interdisciplinary research interest. Episodic foresight is considered a complex
      form of prospection that enables people to generate mental models of future
      scenarios with which to guide actions. In this article, we systematically review
      the available episodic foresight measurement instruments. PubMed and PsycInfo
      were searched through July, 2017 and manual searches of published reviews and
      snowball searches of included studies were also performed. The initial search
      yielded 970 records after the removal of duplicates, of which 363 underwent full
      text screening. Studies that did not measure the imagination of future scenarios
      in adult humans, or that were not reported in English, were excluded. The review
      consists of 303 articles classified into two broad categories, content measures
      and generation measures, that were further subdivided into one or more of six
      subcategories: (i) phenomenology (60%); (ii) examination (49%); (iii) fluency
      (12%); (iii) reaction time (12%); sentence completion (5%); and thought sampling
      (2%). We catalogue the available instruments in these sections, and provide a
      summary overview of each category. Following phenomenological measures, the
      adapted Autobiographical Interview and measures of specificity were the most
      frequently used instruments. We conclude that none of the available instruments
      have been appropriately validated for use, and therefore suggest caution with the
      use of any of the included measures. The development of behavioural measures
      designed to capture degrees of episodic foresight ability in functionally
      relevant contexts among humans would provide a major advance over the currently
      available instruments.

PMID- 30274669
TI  - The medication debate: time to change the record.

PMID- 30274670
TI  - Traumatic brain injury and dementia.

PMID- 30274671
TI  - Traumatic brain injury and dementia.

PMID- 30274672
TI  - Traumatic brain injury and dementia - Authors' reply.

PMID- 30274673
TI  - Age and major depressive disorder: what factors should be investigated? -
      Authors' reply.

PMID- 30274674
TI  - Age and major depressive disorder: what factors should be investigated?

PMID- 30274675
TI  - Mauritius needs to address mental illness, starting in schools.

PMID- 30274676
TI  - The growing problem of mephedrone use in Warsaw, Poland, 2010-18.

PMID- 30274678
TI  - Casinos in Japan.

PMID- 30274679
TI  - Between republicans and freemasons: A lost zoological collection found in a very
      particular school.
AB  - A lost zoological collection was found in an old school in Lisbon, Portugal.
      Taxidermied animals, fauna preserved in glass jars, skeletons, and fossilized
      shells were all part of this collection. The research showed that those animals
      were used by libertarian teachers in science classes in a school created by
      republicans and freemasons in the transition from the 19th to the 20th century.

PMID- 30274681
TI  - Renal transplant recipients receiving loop diuretic therapy have increased
      urinary tract infection rate and altered medullary macrophage polarization marker
      expression.
AB  - Loop diuretics deplete the renal cortico-medullary salt gradient that has
      recently been established as a major modulator of immune responses. Renal
      transplant recipients suffer from a markedly increased rate of urinary tract
      infections (UTIs). Whether diuretic therapy affects renal macrophage polarization
      in the human kidney graft and the incidence of UTI have not been reported. In a
      cohort of 112 adult renal allograft recipients, loop diuretic therapy
      significantly correlated with the rate of UTI during five years after
      transplantation in uni- and multivariable regression analysis. The M1 macrophage
      marker human leukocyte antigen-DR (HLA-DR) and the M2 macrophage marker CD206 co
      localized with the pan-macrophage marker CD68 in the kidney graft. Both were more
      common in renal medulla than cortex. With increasing loop diuretic dose, the
      renal medullary M1/M2 macrophage marker ratio decreased in early surveillance
      biopsies of this cohort. In vitro, the sodium chloride concentration dose
      dependently increased monocyte chemotactic cytokine CCL2 production in human
      myeloid and renal tubular epithelial cells. More CCL2 was detected in the renal
      medulla than cortex of the kidney grafts. However, in patients receiving loop
      diuretic therapy, the renal cortico-medullary CCL2 gradient was diminished and
      CCL2 serum levels decreased significantly. Thus, diuretic therapy associated with
      increased bacteriuria and leukocyturia after kidney transplantation and a
      decreased M1/M2 macrophage marker ratio in the renal medulla. Hence, adjustment
      of diuretic therapy should be investigated further as a possible approach in
      patients with frequent UTIs.

PMID- 30274680
TI  - [Opioid switch and change of route of administration in cancer patients treated
      by morphine].
AB  - This paper reviewed the 2002 guidelines established by the National Federation of
      Cancer Centres. A group of experts nominated by the 3 French Societies involved
      in the treatment of cancer pain (AFSOS, SFAP, SFETD), established new guidelines
      ratios for morphine switching and/or changing of route of administration, in
      patients for whom either pain was not adequatly managed or adverse effects were
      unbearable. After a rapid reminder of the pharmacokinetics and metabolism
      properties of morphine, experts explained why the theory of opioid rotation
      (oxycodone, hydromorphone, fentanyl, methadone, tapentadol) using fixed
      equianalgesic ratios is not any more appropriate for a secure clinical practice.
      In the light of recent publications enhancing our knowledge on the efficacy of
      new drug switching ratios and for changing the route of administration of
      morphine, the group of experts recommended to use reconsidered switching ratios
      favoring security upon efficacy, to minimize overdosing and adverse effects.
      Consequently, after the new conversion ratio (using slow release opioids) was
      applied, a second titration should be done by means of normal release rescue
      formulations for breakthrough pain episodes. A smartphone App. OpioConvert(r)
      will be available for rapid and secure dose conversions.

PMID- 30274683
TI  - Development of a Tissue-Mimicking Phantom of the Brain for Ultrasonic Studies.
AB  - Constructing tissue-mimicking phantoms of the brain for ultrasonic studies is
      complicated by the low backscatter coefficient of brain tissue, causing
      difficulties in simultaneously matching the backscatter and attenuation
      properties. In this work, we report on the development of a polyvinyl alcohol
      based tissue-mimicking phantom with properties approaching those of human brain
      tissue. Polyvinyl alcohol was selected as the base material for the phantom as
      its properties can be varied by freeze-thaw cycling, variations in concentration
      and the addition of scattering inclusions, allowing some independent control of
      backscatter and attenuation. The ultrasonic properties (including speed of sound,
      attenuation and backscatter) were optimized using these methods with talc powder
      as an additive. It was determined that the ultrasonic properties of the phantom
      produced in this study are best matched to brain tissue in the frequency range 1
      3 MHz, indicating its utility for laboratory ultrasonic studies in this frequency
      range.

PMID- 30274682
TI  - Effect of Molecular Weight on Sonoporation-Mediated Uptake in Human Cells.
AB  - Ultrasound-induced microbubble destruction can enhance drug delivery to cells.
      The molecular weight of therapeutic compounds varies significantly (from <1 kDa
      for small molecule drugs, to 7-15 kDa for siRNAs/miRNAs, to >1000 kDa for DNA
      plasmids). Therefore, the objective of this study was to determine the
      relationship between uptake efficiency and molecular weight using equal molar
      concentrations. Uptake efficiency of fluorescent compounds with different
      molecular weights (0.3, 10 and 2000 kDa) was explored in vitro using human
      cardiac mesenchymal cells and breast cancer cells exposed to microbubbles and 2.5
      MHz ultrasound pulses. Uptake by viable cells was quantified using flow
      cytometry. After correction for the fluorescence yield of each compound, there
      was a significant size-dependent difference in fluorescence intensity, indicating
      an inverse relationship between size and uptake efficiency. These results suggest
      that diffusion of therapeutic compounds across permeabilized cell membranes may
      be an important mechanism for ultrasound-mediated drug delivery.

PMID- 30274684
TI  - Neuroradiological findings in patients with "non-lesional" focal epilepsy
      revealed by research protocol.
AB  - AIM: To evaluate whether a dedicated epilepsy research protocol with expert image
      re-evaluation can increase identification of patients with lesions and to attempt
      to ascertain the potential reasons why lesions were not identified previously on
      earlier clinical magnetic resonance imaging (MRI). MATERIALS AND METHODS: Forty
      three patients (26 female) with focal refractory epilepsy who had failed at least
      two trials of anti-epileptic drug treatments were studied. Patients were
      recruited prospectively into the study if previous clinical MRI was deemed to be
      "non-lesional" by the clinicians involved in the initial assessment. Three
      dimensional (3D) T1-weighted (T1W), T2-weighted (T2W), T2 fluid-attenuated
      inversion recovery (T2-FLAIR) sequences, and two-dimensional (2D) coronal T1-/T2W
      FLAIR were assessed by a neuroradiologist, including the previous clinical MRI of
      individual patients. RESULTS: Twenty-nine or 43 (67%) patients remained MRI
      negative after scanning with the epilepsy-dedicated protocol and image
      reappraisal by expert consultant neuroradiologists; however, 14/43 (33%) patients
      were found to have potentially epileptogenic brain lesions. The lesion that most
      frequently escaped the attention of clinicians was hippocampal sclerosis (nine
      cases, of which two had an additional focal cortical dysplasia, FCD), followed by
      single FCDs (two cases), and others including gliosis, encephalocoele, and
      amygdala enlargement (one case each). Eleven of the 14 (79%) previously "non
      lesional" patients had electroencephalogram (EEG) imaging-concordant localisation
      features, rendering them potential candidates for resective surgery. CONCLUSIONS:
      The primary factors explaining the newly identified lesions were the choice of
      MRI sequences, imaging parameters, data quality, lesion not reported (human
      factor), and loss of information through incomplete documentation. It is
      important for all clinicians to proceed meticulously in the detailed assessment
      of epilepsy-dedicated in-vivo MRI and discuss difficult patient cases in
      multidisciplinary team meetings.

PMID- 30274685
TI  - MiR-137 suppresses migration and invasion by targeting EZH2-STAT3 signaling in
      human hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and
      aggressive human malignancies and many cell-intrinsic identities and extrinsic
      epigenetic factors influence the metastatic potential of HCC cells. MicroRNA-137
      is often found to be acting as tumor suppressors, however, how miR-137 involved
      in the metastasis progression in human HCC remains unclear. METHOD: QPCR was
      performed to detect the miR-137 mRNA levels in HCC cell linesand normal liver
      cell line HL7702.Then transwell assay and wound-healing assay were determined to
      investigate the motility of HCC cells introduced into lentivirus to ectopically
      upregulate endogenous miR-137 and EAH2 expressions. Targeting of enhancer of
      zeste homolog 2 (EZH2) gene by miR-137 in HCC was assessed by dual-luciferase
      activity assay and qPCR. Western blot was applied to explore the mechanism. In
      vivo, lung metastasis were evaluated using a mice tail vein injection model.
      RESULTS: In this study, we found that miR-137 is decreased in HCC cell lines and
      had an inhibitory effect on HCC migration and invasion in vitro. EZH2 was a
      direct downstream target gene of miR-137 in HCC and miR-137 suppressed invasion
      and migration by targeting EZH2-STAT3 signaling in HCC cells. Furthermore, EZH2
      overexpression reversed the miR-137 mimics-induced inhibitory effects on
      migration and invasion of HCC cells. In addition, miR-137 inhibited lung
      metastasis of HCC in vivo by targeting EZH2-STAT3 signaling. CONCLUSION: MiR-137
      suppressed migration and invasion by targeting EZH2-STAT3 signaling pathway in
      HCC cells in vitro and in vivo, suggesting miR-137-EZH2-STAT3 may be a potential
      therapeutic target for treatment of human hepatocellular carcinoma.

PMID- 30274686
TI  - Hypoxia inducible factor 1alpha in hepatocellular carcinoma with cirrhosis:
      Association with prognosis.
AB  - BACKGROUND: Hypoxia inducible factor 1alpha (HIF-1alpha) is a protein related
      with carcinogenesis and metastasis in many tumors. However, little is known about
      the prognostic value of HIF-1alpha in hepatocellular carcinoma (HCC) patients
      with cirrhosis. METHODS: Clinical-pathological information and follow-up data
      were collected from HCC (n = 419) and chronic hepatitis (n = 49) patients. HIF
      1alpha expression was scored based on the percentage of immunohistochemical
      staining. Correlations between HIF-1alpha expression and clinical features were
      evaluated by Chi-square test. And survival analysis was performed by multivariate
      Cox regression analysis. RESULTS: In cirrhosis patients, the frequency of HIF
      1alpha positive expression in HCC was higher than in chronic hepatitis (P =
      0.002). HIF-1alpha positive expression was significantly associated with vascular
      invasion (P = 0.002), TNM stage (P = 0.005), HBV infection (P = 0.005), tumor
      size (P = 0.025) and portal vein tumor thrombus (P = 0.001) in HCC with liver
      cirrhosis. While, in cirrhosis-free patients, HIF-1alpha positive expression had
      a significant correlation with vascular invasion (P = 0.039) and AFP value (P =
      0.001) in. HIF-1alpha "positive" had decreased overall survival compared to HIF
      1alpha "negative" patients and this was an independent adverse prognostic factor
      (multivariable analysis P = 0.001) for HCC patients with cirrhosis, but not for
      cirrhosis-free patients. CONCLUSIONS: Our results suggested that HIF-1alpha
      served as a poor prognostic factor for HCC patients with cirrhosis.

PMID- 30274687
TI  - Obesity and bowel cancer: from molecular mechanisms to interventions.
AB  - The purpose of this review article is to examine the evidence of the mechanisms
      linking obesity with bowel cancer risk and to comment on the development of
      interventions that may lower risk of this common age-related disease. The choice
      of topics for inclusion reflects my personal research on the etiology and
      prevention of bowel cancer over the past 3 decades. I have cited literature which
      addresses each of these topics, but because of the breadth of the review article,
      I have not attempted to do this systematically. The accumulation of genomic
      damage which leads to colorectal (bowel) cancer (CRC) is influenced by the
      balance between damage acquisition through environmental exposures and endogenous
      factors/processes and the effectiveness of genomic repair mechanisms. There is
      now convincing evidence that obesity is associated with increased bowel cancer
      risk, and this increased risk is apparent even among those with Lynch syndrome
      who are genetically predisposed to the disease. It seems likely that genomic
      damage resulting from obesity-related inflammation is a key driver of colorectal
      tumorigenesis, but mechanisms may also include altered insulin/insulin-like
      growth factor 1 signaling which may give tumor cells a competitive advantage. The
      importance of inflammation as a mediator of the effects of obesity is supported
      by the fall in CRC risk which follows sustained exposure to nonsteroidal anti
      inflammatory drug such as aspirin and the abrogation of the excess CRC risk in
      obese patients with Lynch syndrome who were randomized to aspirin. Because the
      available evidence about the effects of weight loss in the obese on CRC risk is
      limited, this should be a high priority for future research. In the meantime, to
      lower the global CRC burden, it would be prudent to institute effective public
      measures to reduce the development of obesity and to enable those who are obese
      to lose weight.

PMID- 30274688
TI  - Productive activities and cognitive decline among older adults in China: Evidence
      from the China Health and Retirement Longitudinal Study.
AB  - This study examines the relationship between productive activities and cognitive
      decline among older adults aged 50 years and over in China and whether this
      relationship varies by gender and urban/rural residence using a sample of 13,596
      respondents from three waves of the China Health and Retirement Longitudinal
      Study. Results from Generalized Estimation Equations show that caring for
      grandchildren, caring for a spouse, informal helping and formal volunteering are
      associated with reduced risk of cognitive decline over a two-year period. In
      addition, the types of productive activities that are most beneficial for
      cognition vary by gender and urban/rural residence. Caring for grandchildren and
      volunteering are most beneficial for urban women, informal helping is most
      beneficial for urban men, and paid employment is most beneficial for rural men.

PMID- 30274689
TI  - Periprosthetic bone quality affects the fixation of anatomic glenoids in total
      shoulder arthroplasty: in vitro study.
AB  - BACKGROUND: Glenoid loosening, a common complication of shoulder arthroplasty,
      could relate to implant design and bone quality. However, the role of bone
      density has not been tested experimentally yet. In this study, tests on cadaveric
      specimens of varying bone density were performed to evaluate the effects of bone
      quality on loosening of typical anatomic glenoid implants. METHODS: Cadaveric
      scapulae scanned with a quantitative computed tomography scanner to determine
      bone mineral density (BMD) were implanted with either pegged or keeled cemented
      glenoid components and tested under constant glenohumeral load while a humeral
      head component was moved cyclically in the inferior and superior directions.
      Implant superior and inferior edge lifting, defined as displacement from the
      underlying bone, was measured with linear variable differential transducers until
      we reached 23,000 test cycles, and statistical testing was performed for
      differences in edge lifting due to implant design and related to periprosthetic
      BMD. RESULTS: Edge lifting was statistically significant at all time points, but
      on average, implant design had no effect. Lifting was highest in specimens in
      which BMD below the lifting edge was lower, with trends of increased displacement
      with decreased BMD. CONCLUSIONS: Implant lifting was greater in glenoids of lower
      bone density for both implant designs. This finding suggests that fixation
      failure will most likely occur in bone of lower density and that the fixation
      design itself may play a secondary role.

PMID- 30274690
TI  - Structure assisted impurity profiling for rapid method development in liquid
      chromatography.
AB  - The use of trial-and-error principles is a frequently used technique in method
      development. This may lead to the fact that analytical methods are used routinely
      without developers and users having gained extensive and well-founded knowledge
      about the robustness of their analytical methods and the influence of critical
      key parameters. This very often leads to unnecessary problems for analysts. A
      simple way in reverse phase chromatography to simulate the effects of pH value
      changes on the separation and retention of substances is the pH-dependent
      calculation of the logD value. With this tool, model substances were used to show
      how the time requirement for method screening can be considerably reduced in
      silico and, in addition, extended knowledge about the separation mechanics can be
      generated. Based on this knowledge, a new method for the purity analysis of
      carbamazepine was developed within a very short period of time, which improves
      the performance of the official Ph.Eur. monograph by far. Furthermore, the
      extremely high robustness of the new method was demonstrated. Using the logD
      based approach, Quality-by-Design is applied in method development and kept pace
      with the increasing requirements of regulatory authorities in the pharmaceutical
      industry.

PMID- 30274691
TI  - Development of a quantitative method for four photocyanine isomers using
      differential ion mobility and tandem mass spectrometry and its application in a
      preliminary pharmacokinetics investigation.
AB  - Photodynamic therapy (PDT) has been accepted as an alternative treatment for
      cancer, and its target specificity can be achieved by controlling the location at
      which light activates the photosensitizer. Photocyanine, a novel anticancer
      phthalocyanine-based photosensitizer, is a mixture of 4 cis-isomers of a series
      of synthetic products, and accordingly, it is essential to verify whether there
      are differences in pharmacokinetics among the four isomers for clinical
      application, which requires reliable analytical methods to measure the plasma
      concentrations of the four isomers. An efficient LC-MS/MS method coupled with
      differential mobility spectrometry (DMS) for the simultaneous quantification of
      the four photocyanine isomers in human plasma was developed and validated herein.
      This method had a limit of quantification of 10 ng mL-1 for each isomer and
      showed stable and reproducible inter- and intra-day results. Use of this method
      in preliminary pharmacokinetic studies in patients with esophageal cancer showed
      that the exposure and distribution of the four isomers were different, which had
      not been found in previous studies. The present research revealed that DMS was an
      effective tool for isomeric quantitation and that LC-DMS-MS/MS presented robust
      and reliable in biomatrix analysis. The method significantly improved peak
      separation and sensitivity compared with that of other LC-MS-based methods.

PMID- 30274692
TI  - Monolithic column with polymeric deep eutectic solvent as stationary phase for
      capillary electrochromatography.
AB  - A novel monolithic column based on the copolymerization of ethylene
      dimethacrylate and a deep eutectic solvent (DES), which composed of chlorocholine
      chloride and itaconic acid, was developed for capillary electrochromatography
      (CEC). The structure and morphology of the obtained monolithic column was
      characterized by Fourier transform infrared spectra and scanning electron
      microscopy, which showed a porous monolithic structure with good permeability.
      The influence of pH value and acetonitrile content on electroosmotic flow (EOF)
      of DES-based monolithic column was investigated. The DES-based monolithic column
      was used as the separation column of CEC and exhibited excellent performance for
      the separation of neutral compounds, phenols, toluidines, nucleosides, nucleotide
      bases and alkaloids. The retention mechanism might be attributed to synergistic
      effect of hydrophobic interaction, hydrogen bond interaction and electronic
      interaction. The DES-based monolithic column showed good repeatability with
      relative standard deviations of migration time less than 0.80%, 2.15%, 4.26% and
      3.08% for intra-day, inter-day, column-to-column and batch-to-batch,
      respectively. Thus, organic polymer monolithic columns with DESs as functional
      monomers are a promising option in chromatographic separation.

PMID- 30274693
TI  - Analysis of degradation products of nerve agents via post-pentafluorobenzylation
      liquid chromatography-tandem mass spectrometry.
AB  - In the work reported here, a screening procedure was developed for the detection
      and identification of RMPAs (nerve agent degradation products) after
      pentafluorobenzylation using liquid chromatography-tandem mass spectrometry (LC
      MS/MS). With this method, all RMPAs, including highly hydrophilic types such as
      methylphosphonic acid (MPA) and ethyl methylphosphonic acid (EMPA), were
      sufficiently retained in commonly used reversed-phase columns (retention times:
      15.7 and 11.0 min.), and the presence of RMPAs was determined more efficiently
      than with the conventional direct LC-MS/MS method. The detection limits of RMPAs
      using this approach (<33 ng) were mostly superior to those observed with direct
      LC-MS/MS (<74 ng) and gas chromatography-mass spectrometry (GC-MS) after
      pentafluorobenzylation (<1.1 MUg). The applicability of newly developed method
      toward real samples was evaluated via recovery tests involving urine/serum and
      wipe tests on various surfaces.

PMID- 30274695
TI  - [Oncoplastic breast surgery].
AB  - Oncoplastic surgery is to treat breast tumors with the help of plastic surgery.
      Efficiency of breast-conserving treatments (BCT) compared to mastectomies is
      equivalent. BCT is better accepted but can cause breast deformity, thus further
      operations. Oncoplastic surgery aims at conserving an acceptable shape to the
      breast. It ranges from simple remodeling to more complex techniques modifying the
      width of the breast. According to the quadrant to treat (inner upper, outer
      upper, inner lower, outer lower, union of quadrants, tumors of the nipple-areola
      complex, tumors of the inframammary fold), according to the proximity of the
      tumor to the nipple, and to the size of the breast and tumor, various techniques
      are displayed. Few touch ups are necessary. Symmetry is managed during the
      initial operation or after.

PMID- 30274694
TI  - Radiosynthesis and evaluation of a fluorine-18 labeled radioligand targeting
      vesicular acetylcholine transporter.
AB  - Vesicular acetylcholine transporter (VAChT) is a reliable biomarker for assessing
      the loss of cholinergic neurons in the brain that is associated with cognitive
      impairment of patients. 5-Hydrotetralin compound (+/-)-5-OH-VAT is potent (Ki =
      4.64 +/- 0.32 nM) and selective for VAChT (>1800-fold and 398-fold for sigma1 and
      sigma2 receptor, respectively) with favorable hydrophilicity (LogD = 1.78), while
      (-)-5-OH-VAT originally serves as the radiolabeling precursor of (-)-[18F]VAT, a
      promising VAChT radiotracer with a logD value of 2.56. To evaluate (-)-5-OH
      [18F]VAT as a radiotracer for VAChT, we performed in vitro binding assay to
      determine the potency of the minus enantiomer (-)-5-OH-VAT and plus enantiomer
      (+)-5-OH-VAT, indicating that (-)-5-OH-VAT is a more potent VAChT enantiomer.
      Radiosynthesis of (-)-5-OH-[18F]VAT was explored using three strategies. (-)-5-OH
      [18F]VAT was achieved with a good yield (24 +/- 6%) and high molar activity (~37
      GBq/umol, at the end of synthesis) using a microwave assisted two-step one-pot
      procedure that started with di-MOM protected nitro-containing precursor (-)-6.
      MicroPET studies in the brain of nonhuman primate (NHP) suggest that (-)-5-OH
      [18F]VAT readily penetrated the blood brain barrier and specifically accumulated
      in the VAChT-enriched striatum with improved washout kinetics from striatum
      compared to [18F]VAT. Nevertheless, the lower target to non-target ratio may
      limit its use for in vivo measurement of the VAChT level in the brain.

PMID- 30274696
TI  - One-Stage Repair of Adult Aortic Coarctation and Concomitant Cardiac Diseases:
      Ascending to Abdominal Aorta Extra-Anatomical Bypass Combined with Cardiac
      Surgery.
AB  - BACKGROUND: To evaluate one-stage repair with ascending to abdominal aorta extra
      anatomical bypass combined with cardiac surgery for adult aortic coarctation
      (COA) concomitant with cardiac diseases. METHODS: Between February 2009 and
      September 2016, 24 consecutive patients (79.17% male, mean age 36.04+/
      13.67years) with COA and concomitant cardiac diseases underwent one-stage repair
      (ascending to abdominal aorta extra-anatomical bypass combined with cardiac
      surgery). Two patients who underwent off-pump coronary artery surgery combined
      with ascending to abdominal aorta bypass did not require cardiopulmonary bypass.
      Twenty-two patients underwent one-stage repair under cardiopulmonary bypass.
      RESULTS: No in-hospital mortality was observed. There was a significant reduction
      in baseline systolic blood pressure from 159.80+/-23.58 to 127.0+/-6.86mmHg. Mean
      upper-lower limb blood gradient pressure decreased significantly from 37.80+/
      8.73 to 11.47+/-2.12mmHg after surgery. Two patients required prolonged
      mechanical ventilation for respiratory dysfunction. One patient needed temporary
      continuous renal replacement therapy. No re-exploration for bleeding and
      gastrointestinal complications was needed. There was no postoperative paraplegia
      or permanent neurological abnormalities. Grafts were patent for all patients and
      no graft-related complications were observed in the hospital. Median follow-up
      was 41.50 months [interquartile range (IQR) 16.75-64.50 months] and 6-year
      survival was 76.39%. Median number of antihypertensive drugs was 0 (IQR 0-1),
      which was a significant reduction compared with preoperative drugs (2, IQR 1-3).
      CONCLUSIONS: Ascending to abdominal extra-anatomical aorta bypass combined with
      cardiac surgery is a safe and effective one-stage repair technique for patients
      with COA concomitant with cardiac diseases.

PMID- 30274697
TI  - Gene Function Discovery for Kinetoplastid Pathogens.
AB  - We propose to integrate the existing and new experimental data with computational
      tools to model interaction networks for the most prominent kinetoplastid
      pathogens. These interaction networks will vastly expand the functional
      annotation of the kinetoplastid genomes, which in turn are critical for
      identifying new routes of disease intervention.

PMID- 30274698
TI  - Bladder Tumors with Mixed Histology: What Is the Basis for the Heterogeneity?

PMID- 30274700
TI  - Lessons Learned from the Global Epidemiology of Kidney Cancer: A Refresher in
      Epidemiology 101.

PMID- 30274699
TI  - Radiofrequency-induced Thermo-chemotherapy Effect Versus a Second Course of
      Bacillus Calmette-Guerin or Institutional Standard in Patients with Recurrence of
      Non-muscle-invasive Bladder Cancer Following Induction or Maintenance Bacillus
      Calmette-Guerin Therapy (HYMN): A Phase III, Open-label, Randomised Controlled
      Trial.
AB  - BACKGROUND: There is no effective intravesical second-line therapy for non-muscle
      invasive bladder cancer (NMIBC) when bacillus Calmette-Guerin (BCG) fails.
      OBJECTIVE: To compare disease-free survival time (DFS) between radiofrequency
      induced thermo-chemotherapy effect (RITE) and institutional standard second-line
      therapy (control) in NMIBC patients with recurrence following
      induction/maintenance BCG. DESIGN, SETTINGS, AND PARTICIPANTS: Open-label, phase
      III randomised controlled trial accrued across 14 centres between May 2010 and
      July 2013 (HYMN [ClinicalTrials.gov: NCT01094964]). INTERVENTION: Patients were
      randomly assigned (1:1) to RITE (60min, 40mg mitomycin-C, 42+/-2 degrees C) or
      control following stratification for carcinoma in situ (CIS) status
      (present/absent), therapy history (failure of previous induction/maintenance
      BCG), and treatment centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Primary outcome measures were DFS and complete response (CR) at 3 mo for the CIS
      at randomisation subgroup. Analysis was based on intention-to-treat. RESULTS AND
      LIMITATIONS: A total of 104 patients were randomised (48 RITE: 56 control).
      Median follow-up for the 31 patients without a DFS event was 36 mo. There was no
      significant difference in DFS between treatment arms (hazard ratio [HR] 1.33, 95%
      confidence interval [CI] 0.84-2.10, p=0.23) or in 3-mo CR rate in CIS patients
      (n=71; RITE: 30% vs control: 47%, p=0.15). There was no significant difference in
      DFS between treatment arms in non-CIS patients (n=33; RITE: 53% vs control: 24%
      at 24 mo, HR 0.50, 95% CI 0.22-1.17, p=0.11). DFS was significantly lower in RITE
      than in control in CIS with/without papillary patients (n=71; HR 2.06, 95% CI
      1.17-3.62, p=0.01; treatment-subgroup interaction p=0.007). Disease progression
      was observed in four patients in each treatment arm. Adverse events and health
      related quality of life between treatment arms were comparable. CONCLUSIONS: DFS
      was similar between RITE and control. RITE may be a second-line therapy for non
      CIS recurrence following BCG failure; however, confirmatory trials are needed.
      RITE patients with CIS with/without papillary had lower DFS than control. HYMN
      highlights the importance of the control arm when evaluating novel therapies.
      PATIENT SUMMARY: This study did not show a difference in bladder cancer outcomes
      between microwave-heated chemotherapy and standard of care treatment. Papillary
      bladder lesions may benefit from microwave-heated chemotherapy treatment;
      however, more research is needed. Both treatments are similarly well tolerated.

PMID- 30274701
TI  - The Cancer Immunogram as a Framework for Personalized Immunotherapy in Urothelial
      Cancer.
AB  - CONTEXT: The abysmal outlook of urothelial cancer (UC) has changed with the
      introduction of immunotherapy. Still, many patients do not respond and
      distinctive biomarkers are currently lacking. The rise of this novel
      armamentarium of immunotherapy treatments, in combination with the complex
      biology of an immunological tumor response, warrants the development of a
      comprehensive framework that can provide an overview of important immunological
      processes at play in individual patients. OBJECTIVE: To develop a comprehensive
      framework based on tumor- and host-specific parameters to understand
      immunotherapy response in UC. This framework can inform rational, biology-driven
      clinical trials and ultimately guide us toward individualized patient treatment.
      EVIDENCE ACQUISITION: A literature review was conducted on UC immunotherapy,
      clinical trial data, and biomarkers of response to checkpoint inhibition.
      EVIDENCE SYNTHESIS: Here, we propose a UC immunogram, based on currently
      available clinical and translational data. The UC immunogram describes several
      tumor- and host-specific parameters that are required for successful
      immunotherapy treatment. These seven parameters are tumor foreignness, immune
      cell infiltration, absence of inhibitory checkpoints, general performance and
      immune status, absence of soluble inhibitors, absence of inhibitory tumor
      metabolism, and tumor sensitivity to immune effectors. CONCLUSIONS: Longitudinal
      integration of individual patient parameters may ultimately lead to personalized
      and dynamic immunotherapy, to adjust to the Darwinian forces that drive tumor
      evolution. Incorporating multiparameter biomarkers into quantitative predictive
      models will be a key challenge to integrate the immunogram into daily clinical
      practice. PATIENT SUMMARY: Here, we propose the urothelial cancer immunogram, a
      novel way of describing important immunological characteristics of urothelial
      cancer patients and their tumors. Seven characteristics determine the chance of
      having an immunological tumor response. Using this immunogram, we aim to better
      understand why some patients respond to immunotherapy and some do not, to
      ultimately improve anticancer therapy.

PMID- 30274702
TI  - Primary Whole-gland Cryoablation for Prostate Cancer: Biochemical Failure and
      Clinical Recurrence at 5.6 Years of Follow-up.
AB  - : We retrospectively evaluated complications and functional and oncologic
      outcomes of 94 consecutive men who underwent primary whole-gland cryoablation for
      localized prostate cancer (PCa) from 2002 to 2012. Kaplan-Meier and multivariable
      Cox regression analyses were performed using a landmark starting at 6 mo of
      follow-up. In total, 75% patients had D'Amico intermediate- (48%) or high- (27%)
      risk PCa. Median follow-up was 5.6 yr. Median time to prostate-specific antigen
      (PSA) nadir was 3.3 mo, and 70 patients reached PSA <0.2ng/ml postcryoablation.
      The 90-d high-grade (Clavien Grade IIIa) complication rate was 3%, with no rectal
      fistulas reported. Continence and potency rates were 96% and 11%, respectively.
      The 5-yr biochemical failure-free survival (PSA nadir+2ng/ml) was 81% overall and
      89% for low-, 78% for intermediate-, and 80% for high-risk PCa (p=0.46). The
      median follow-up was 5.6 and 5.1 yr for patients without biochemical failure and
      with biochemical failure, respectively. The 5-yr clinical recurrence-free
      survival was 83% overall and 94% for low-, 84% for intermediate-, and 69% for
      high-risk PCa (p=0.046). Failure to reach PSA nadir <0.2ng/ml within 6 mo
      postcryoablation was an independent predictor for biochemical failure (p=0.006)
      and clinical recurrence (p=0.03). The 5-yr metastases-free survival was 95%. Main
      limitation is retrospective evaluation. Primary whole-gland cryoablation for PCa
      provides acceptable medium-term oncologic outcomes and could be an alternative
      for radiation therapy or radical prostatectomy. PATIENT SUMMARY: Cryoablation is
      a safe, minimally-invasive procedure that uses cold temperatures delivered via
      probes through the skin to kill prostate cancer (PCa) cells. Whole-gland
      cryoablation may offer an alternative treatment option to surgery and
      radiotherapy. We found that patients had good cancer outcomes 5 yr after whole
      gland cryoablation, and those with a prostate-specific antigen value >=0.2ng/ml
      within 6 mo after treatment were more likely to have PCa recurrence.

PMID- 30274703
TI  - Towards Next-generation Urine-based Prostate Cancer Risk Stratification.

PMID- 30274704
TI  - Results and functional outcomes of en-bloc resection and vascular reconstruction
      in extremity musculoskeletal tumors.
AB  - OBJECTIVES: This paper aims to evaluate the extremity function and vascular
      outcome after limb-sparing surgery for extremity musculoskeletal tumors invading
      vascular structure required reconstruction. METHODS: Of the 507 patients with
      musculoskeletal tumors, who underwent surgery between 2004 and 2007, 17 (3,3%)
      patients with major vessel involvement were included in the study. The mean age
      was 37.8 +/- 14.5, with a female/male ratio of 8/9. Thirteen (76.4%) patients had
      Stage IIb disease, and 2 (11,7%) patients had Stage III disease. In 2 (11,7%)
      patients have locally aggressive tumor that had Stage 3. Fifteen (88.2%) of the
      cases involved lower extremity, whilst 2 (11.8%) of them involved upper
      extremity. An arterial reconstruction was carried out in all patients. Wide tumor
      resection and endoprosthetic reconstruction were performed in 6 (35.2%) patients.
      Other 11 (65.8%) patients were treated with wide resection and soft tissue
      reconstruction. Postoperative data included; perioperative morbidities such as
      bleeding, infection, graft thrombosis, rupture, metastatic local recurrence and
      mortality. Ankle brachial index (ABI) and color-flow-duplex-scan (CFDS) were done
      at the final follow-up of the study, in order to prove the efficacy of
      reconstruction. Functional outcome was evaluated with International Society of
      Limb Salvage (ISOLS) criteria. RESULTS: The mean follow-up was of 39 months
      (range 3-120). Perioperative complications were arterial graft thrombosis
      occurred in 3 (17.6%) patients treated acutely with thrombectomy, uncontrolled
      deep wound infection occurred in 2 patients whom extremities were amputated. The
      most frequent complication after surgery was limb edema according to possibly
      venous and lymphatic obstruction, staged as C1, C2 and C3 disease was established
      in 6 patients (two patients in each group), and 1 patient was classified as C6
      disease. Three (17.6%) patients had local recurrence (1/3 patient died and 2/3
      (11.7%) patients underwent transfemoral amputation). At the last follow-up, 9
      (52.9%) patients were alive without evidence of disease, 8 (47.1%) patients were
      died due to primary disease. There were 8 (47.1%) patients alive with an intact
      limb. Although functional outcome scores were satisfactory, emotional acceptance
      scores were low. The limb salvage probability was 74.0%. CONCLUSION: Limb-sparing
      oncological surgery in musculoskeletal tumors with vascular invasion provides a
      satisfactory limb function, which may lead to an improved life quality. Arterial
      reconstruction has a high rate of patency in the long term. The surgeon should be
      aware of early perioperative complication related to vascular reconstruction and
      infection that effect on the rate of extremity survival. LEVEL OF EVIDENCE: Level
      IV, Therapeutic study.

PMID- 30274706
TI  - Children's fairness in two Chinese schools: A combined ethnographic and
      experimental study.
AB  - Recent research has shown that children's sense of fairness is shaped in part by
      cultural practices, values, and norms. However, the specific social factors that
      motivate children's fairness decisions remain poorly understood. The current
      study combined an ethnographic approach with experimental tests of fairness (the
      Inequity Game) in two Chinese schools with qualitatively different practices and
      norms. In the "University school," children received explicit moral instruction
      on fairness reinforced by adults when supervising children's activities. By
      contrast, in the "Community school," children received less formal moral
      education and little adult supervision during play time, but norms of cooperation
      and fairness emerged through informal interactions with peers and other members
      of the community. Contrary to our predictions, children in both schools (N = 66)
      rejected both disadvantageous and advantageous allocations of resources in the
      test trials. However, in the very first practice trials, children from the
      Community school tended to reject all inequalities, whereas children from the
      University school tended to accept inequalities. We draw on the ethnographies of
      the schools to interpret these results, concluding that, despite the similarities
      in the experimental results, different motivations and social factors likely
      underlie the rejection of inequality in the two schools.

PMID- 30274705
TI  - DynBench3D, a Web-Resource to Dynamically Generate Benchmark Sets of Large
      Heteromeric Protein Complexes.
AB  - Multi-protein machines are responsible for most cellular tasks, and many efforts
      have been invested in the systematic identification and characterization of
      thousands of these macromolecular assemblies. However, unfortunately, the (quasi)
      atomic details necessary to understand their function are available only for a
      tiny fraction of the known complexes. The computational biology community is
      developing strategies to integrate structural data of different nature, from
      electron microscopy to X-ray crystallography, to model large molecular machines,
      as it has been done for individual proteins and interactions with remarkable
      success. However, unlike for binary interactions, there is no reliable gold
      standard set of three-dimensional (3D) complexes to benchmark the performance of
      these methodologies and detect their limitations. Here, we present a strategy to
      dynamically generate non-redundant sets of 3D heteromeric complexes with three or
      more components. By changing the values of sequence identity and component
      overlap between assemblies required to define complex redundancy, we can create
      sets of representative complexes with known 3D structure (i.e., target
      complexes). Using an identity threshold of 20% and imposing a fraction of
      component overlap of <0.5, we identify 495 unique target complexes, which
      represent a real non-redundant set of heteromeric assemblies with known 3D
      structure. Moreover, for each target complex, we also identify a set of
      assemblies, of varying degrees of identity and component overlap, that can be
      readily used as input in a complex modeling exercise (i.e., template
      subcomplexes). We hope that resources like this will significantly help the
      development and progress assessment of novel methodologies, as docking benchmarks
      and blind prediction contests did. The interactive resource is accessible at
      https://DynBench3D.irbbarcelona.org.

PMID- 30274707
TI  - Pediatric sternal fractures from a Level 1 trauma center.
AB  - BACKGROUND/PURPOSE: Sternal fractures are rare in children. The purpose of this
      series is to document traumatic findings in pediatric patients with sternal
      fractures at a Level 1 trauma center. STUDY DESIGN: We reviewed the charts of
      patients with radiologically confirmed sternal fractures from a trauma database
      at a pediatric Level 1 trauma center between January 1, 2000 and December 31,
      2015. We report mechanisms of injury, associated injuries, complications, and
      outcomes associated with sternal fractures. RESULTS: Over the 16-year period,
      19/25,781 (0.07%) admitted patients had radiologically confirmed sternal
      fractures. 15/19 (78.9%) patients were male. The median age was 14 years, with
      interquartile range 10-16 years. 7/19, (36.8%) were sustained owing to motor
      vehicle accidents. Associated injuries included substernal hematoma (n = 6),
      pulmonary contusion (n = 4), vertebral injury (n = 2), rib fracture (n = 4),
      intraabdominal injury (n = 3), pneumothorax (n = 3), long bone injury (n = 3)
      traumatic brain injury (n = 2), hemothorax (n = 2), pneumomediastinum (n = 2) and
      cardiac contusion (n = 1). CONCLUSIONS: In this series, pediatric sternal
      fractures were caused by high velocity mechanisms and had significant
      comorbidity. While patients with isolated sternal fractures may be candidates for
      emergency department discharge, a thorough evaluation should be performed in
      children with sternal fractures to identify concurrent injuries. LEVEL OF
      EVIDENCE: Level IV.

PMID- 30274708
TI  - Clinical features, treatment, and outcomes of bilateral Wilms' tumor: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Wilms' tumor(WT) is the most common malignant renal tumor of
      childhood. Despite the good prognosis of WT, bilateral Wilms' tumor (BWT) still
      has a poor outcome. We systematically reviewed the literature on BWT, aiming to
      define its clinical features, treatment, and outcomes. METHODS: PubMed, OVID
      EMbase, Web of Science, and Cochrane Library were systematically searched for
      studies published from 1980 to 2017. Case series and comparative studies reported
      clinical data of BWT patients were included. RESULTS: A total of 32 studies
      comprising 1457 patients were retained for primary outcome. Hemihypertrophy,
      cryptorchidism, and Beckwith-Wiedemann syndrome(BWS) are the most common
      congenital anomalies and syndrome. 86% of patients had favorable histology (FH).
      Patients with local stage I or II accounted for 64%, and 12.6% had metastasis at
      diagnosis. Bilateral nephron-sparing surgery (NSS) was achieved in 33.8%.
      Recurrence and renal failure occurred in 20% and 8%. The overall survival (OS)
      was 73%. In comparative studies, OS of patients undergoing bilateral NSS was
      similar to that of other operation types. CONCLUSION: Prognosis of BWT has been
      improved but is significantly poorer than WT. Bilateral NSS was recommended by
      most centers to preserve more renal volume. However, finding a balance between
      retaining renal function and avoiding recurrence remains a question. TYPE OF
      STUDY: Systematic review. LEVEL OF EVIDENCE: Level IV.

PMID- 30274709
TI  - Transumbilical repair of umbilical hernia in children: The covert scar approach.
AB  - BACKGROUND: Umbilical hernia repairs are one of the most commonly performed
      operations in children. The traditional repair involves an infraumbilical
      incision, which produces a visible scar. We report a novel technique of umbilical
      hernia repair through a transumbilical incision, which eliminates the scar by
      hiding it within the umbilicus. METHODS: We performed a retrospective chart
      review of 134 patients who had undergone a transumbilical hernia repair at a
      single institution between 2008 and 2016. Satisfaction with cosmesis and the
      presence of complications were assessed through parental interviews during follow
      up visit or by telephone survey. These data were compared to a large volume
      retrospective analysis of the standard infraumbilical approach. RESULTS: 121 of
      the 134 patients were evaluated in the clinic or by telephone interview. The
      overall complication rate was 7.44%. Parents of 118 patients reported
      satisfaction with the cosmetic result (97.52%). In comparison to the largest
      study of pediatric infraumbilical repair, there was an improvement in subjective
      cosmesis without a significant increase in complications. CONCLUSION:
      Transumbilical hernia repair is a safe and cosmetically appealing technique for
      umbilical hernia repair in children. LEVEL OF EVIDENCE: Treatment study, level
      III.

PMID- 30274710
TI  - Vocal cord dysfunction following esophageal atresia and tracheoesophageal fistula
      (EA/TEF) repair.
AB  - BACKGROUND: The purpose of this study was to determine risk factors and long-term
      outcomes in patients with esophageal atresia +/-tracheoesophageal fistula
      (EA/TEF) with vocal cord dysfunction (VCD) owing to recurrent laryngeal nerve
      (RLN) injury. METHOD: A retrospective chart review was performed for EA/TEF
      patients repaired at our institution from 1999 to 2014 (REB #1000032265).
      RESULTS: Of 197 patients, 22 (11.2%) were diagnosed with VCD by indirect
      laryngoscopy following EA/TEF repair. Aspiration was documented on video swallow
      study for 21 patients, and as a result, 13 required thickened feeds and 8
      required gastrostomy tube feeds. Of the 16 H-type TEF patients, 8 (50%) had VCD.
      Following discharge, 20 (90.9%) patients with VCD eventually tolerated full feeds
      orally without aspiration but only 8 (36.4%) had documented recovery of vocal
      cord movement at long-term follow up (mean 452 days). Overall, patients with VCD
      were more likely to have feeding modifications, increased exposure to
      radiological studies, and increased frequency of Otolaryngology follow-up
      compared to EA/TEF patients without VCD. CONCLUSION: EA/TEF patients are at risk
      for VCD. Clinical improvement did not always correlate with recovery of VC
      motion. Strategies to minimize RLN damage will improve outcomes and quality of
      life for EA/TEF patients. LEVEL OF EVIDENCE: Level III.

PMID- 30274711
TI  - Intravenous dexmedetomidine use in obstetric anaesthesia: a weapon in our
      armoury?

PMID- 30274712
TI  - Umbilical artery flow monitoring with transesophageal echocardiography during
      maternal cardiac surgery.

PMID- 30274713
TI  - Sphingosine phosphate lyase insufficiency syndrome (SPLIS): A novel inborn error
      of sphingolipid metabolism.
AB  - Sphingosine-1-phosphate lyase (SPL) is an intracellular enzyme that controls the
      final step in the sphingolipid degradative pathway, the only biochemical pathway
      for removal of sphingolipids. Specifically, SPL catalyzes the cleavage of
      sphingosine 1-phosphate (S1P) at the C2-3 carbon bond, resulting in its
      irreversible degradation to phosphoethanolamine (PE) and hexadecenal. The
      substrate of the reaction, S1P, is a bioactive sphingolipid metabolite that
      signals through a family of five G protein-coupled S1P receptors (S1PRs) to
      mediate biological activities including cell migration, cell
      survival/death/proliferation and cell extrusion, thereby contributing to
      development, physiological functions and - when improperly regulated - the
      pathophysiology of disease. In 2017, several groups including ours reported a
      novel childhood syndrome that featured a wide range of presentations including
      fetal hydrops, steroid-resistant nephrotic syndrome (SRNS), primary adrenal
      insufficiency (PAI), rapid or insidious neurological deterioration,
      immunodeficiency, acanthosis and endocrine abnormalities. In all cases, the
      disease was attributed to recessive mutations in the human SPL gene, SGPL1. We
      now refer to this condition as SPL Insufficiency Syndrome, or SPLIS. Some
      features of this new sphingolipidosis were predicted by the reported phenotypes
      of Sgpl1 homozygous null mice that serve as vertebrate SPLIS disease models.
      However, other SPLIS features reveal previously unrecognized roles for SPL in
      human physiology. In this review, we briefly summarize the biochemistry,
      functions and regulation of SPL, the main clinical and biochemical features of
      SPLIS and what is known about the pathophysiology of this condition from murine
      and cell models. Lastly, we consider potential therapeutic strategies for the
      treatment of SPLIS patients.

PMID- 30274714
TI  - Endocannabinoid and nitric oxide systems of the hypothalamic paraventricular
      nucleus mediate effects of NPY on energy expenditure.
AB  - OBJECTIVE: Neuropeptide Y (NPY) is one of the most potent orexigenic peptides.
      The hypothalamic paraventricular nucleus (PVN) is a major locus where NPY exerts
      its effects on energy homeostasis. We investigated how NPY exerts its effect
      within the PVN. METHODS: Patch clamp electrophysiology and Ca2+ imaging were used
      to understand the involvement of Ca2+ signaling and retrograde transmitter
      systems in the mediation of NPY induced effects in the PVN. Immuno-electron
      microscopy were performed to elucidate the subcellular localization of the
      elements of nitric oxide (NO) system in the parvocellular PVN. In vivo metabolic
      profiling was performed to understand the role of the endocannabinoid and NO
      systems of the PVN in the mediation of NPY induced changes of energy homeostasis.
      RESULTS: We demonstrated that NPY inhibits synaptic inputs of parvocellular
      neurons in the PVN by activating endocannabinoid and NO retrograde transmitter
      systems via mobilization of Ca2+ from the endoplasmic reticulum, suggesting that
      NPY gates the synaptic inputs of parvocellular neurons in the PVN to prevent the
      influence of non-feeding-related inputs. While intraPVN administered NPY
      regulates food intake and locomotor activity via NO signaling, the
      endocannabinoid system of the PVN selectively mediates NPY-induced decrease in
      energy expenditure. CONCLUSION: Thus, within the PVN, NPY stimulates the release
      of endocannabinoids and NO via Ca2+-influx from the endoplasmic reticulum. Both
      transmitter systems appear to have unique roles in the mediation of the NPY
      induced regulation of energy homeostasis, suggesting that NPY regulates food
      intake, energy expenditure, and locomotor activity through different neuronal
      networks of this nucleus.

PMID- 30274715
TI  - Coral reef degradation affects the potential for reef recovery after disturbance.
AB  - The loss of coral cover is often accompanied by an increase of benthic algae, a
      decline in biodiversity and habitat complexity. However, it remains unclear how
      surrounding communities influence the trajectories of re-colonization between
      pulse disturbance events. Over a 12-month field experiment in the central Red
      Sea, we examined how healthy (hard-coral dominated) and degraded (algae
      dominated) reef areas influence recruitment and succession patterns of benthic
      reef foundation communities on bare substrates. Crustose coralline algae and
      other calcifiers were important colonizers in the healthy reef area, promoting
      the accumulation of inorganic carbon. Contrary, substrates in the degraded area
      were predominantly colonized by turf algae, lowering the accumulation of
      inorganic carbon by 178%. While coral larvae settlement similarly occurred in
      both habitats, degraded areas showed 50% fewer recruits. Our findings suggest
      that in degraded reefs the replenishment of adult coral populations is reduced
      due to recruitment inhibition through limited habitat complexity and grazing
      pressure, thereby restraining reef recovery.

PMID- 30274716
TI  - Environmental conditions affect activity and associated microorganisms of marine
      sponges.
AB  - Changes in environmental conditions can influence sponges and their holobionts.
      The present study investigated the effect of upwelling and anthropogenic
      pollution on the bioactivity of marine sponges, microbial communities and
      functional genes, and composition of their chemical compounds. The species
      Dysidea etheria, Darwinella sp., Hymeniacidon heliophila and Tedania ignis were
      collected from areas with distinct influence of upwelling and low anthropogenic
      impact and from areas without influence of upwelling but affected by sewage and
      the port. In most cases, the same sponge species collected from areas with
      distinct environmental conditions had a different chemical composition,
      antifouling activity, composition and diversity of associated microorganisms.
      Antimicrobial, quorum sensing inhibitory and anti-larval activities of sponge
      extracts were more pronounced in the area without upwelling showing higher level
      of anthropogenic pollution. This study suggests that upwelling and anthropogenic
      pollution affect the chemical activity and holobiome composition of sponges.

PMID- 30274717
TI  - Quantitative analysis of fish and invertebrate assemblage dynamics in association
      with a North Sea oil and gas installation complex.
AB  - Decommissioning of offshore infrastructure has become a major issue facing the
      global offshore energy industry. In the North Sea alone, the decommissioning
      liability is estimated at L40 billion by 2040. Current international policy
      requires removal of offshore infrastructure when their production life ends;
      however, this policy is being questioned as emerging data reveal the importance
      of these structures to fish and invertebrate populations. Indeed, some
      governments are developing 'rigs-to-reef' (RTR) policies in situations where
      offshore infrastructure is demonstrated to have important environmental benefits.
      Using Remotely Operated Vehicles (ROVs), this study quantified and analysed fish
      and invertebrate assemblage dynamics associated with an oil and gas (O&G) complex
      in the Dogger Bank Special Area of Conservation (SAC), in the North Sea, Germany.
      We found clear depth zonation of organisms: infralittoral communities (0-15 m),
      circalittoral assemblages (15-45 m) and epi-benthic communities (45-50 m), which
      implies that 'topping' or 'toppling' decommissioning strategies could eliminate
      communities that are unique to the upper zones. Sessile invertebrate assemblages
      were significantly different between structures, which appeared to be driven by
      both biotic and abiotic mechanisms. The O&G complex accommodated diverse and
      abundant motile invertebrate and fish assemblages within which the whelk
      Buccinium undatum, cod fish Gadus morhua and lumpsucker fish Cyclopterus lumpus
      used the infrastructure for different stages of reproduction. This observation of
      breeding implies that the structures may be producing more fish and
      invertebrates, as opposed to simply acting as sites of attraction (sensu the
      'attraction vs production' debate). At present, there are no records of C. lumpus
      spawning at such depth and distance from the coast, and this is the first
      published evidence of this species using an offshore structure as a spawning
      site. Overall, this study provides important new insight into the role of
      offshore O&G structures as habitat for fish and invertebrates in the North Sea,
      thereby helping to inform decommissioning decisions.

PMID- 30274718
TI  - Current practices and knowledge supporting oil spill risk assessment in the
      Arctic.
AB  - Oil spill response (OSR) in the Arctic marine environment conducted as part of
      operational planning and preparedness supporting exploration and development is
      most successful when knowledge of the ecosystem is readily available and
      applicable in an oil spill risk assessment framework. OSR strategies supporting
      decision-making during the critical period after a spill event should be explicit
      about the environmental resources potentially at risk and the efficacy of OSR
      countermeasures that best protect sensitive and valued resources. At present,
      there are 6 prominent methods for spill impact mitigation assessment (SIMA) in
      the Arctic aimed at supporting OSR and operational planning and preparedness;
      each method examines spill scenarios and identifies response strategies best
      suited to overcome the unique challenges posed by polar ecosystems and to
      minimize potential long-term environmental consequences. The different methods
      are grounded in classical environmental risk assessment and the net environmental
      benefit analysis (NEBA) approach that emerged in the 1990s after the Exxon Valdez
      oil spill. The different approaches share 5 primary assessment elements (oil
      physical and chemical properties, fate and transport, exposure, effects and
      consequence analysis). This paper highlights how the different Arctic methods
      reflect this common risk assessment framework and share a common need for oil
      spill science relevant to Arctic ecosystems. An online literature navigation
      portal, developed as part of the 5-year Arctic Oil Spill Response Technologies
      Joint Industry Programme, complements the different approaches currently used in
      the Arctic by capturing the rapidly expanding body of scientific knowledge useful
      to evaluating exposure, vulnerability and recovery of the Arctic ecosystem after
      an oil spill.

PMID- 30274719
TI  - A new approach to testing potential leaching toxicity of fouling release coatings
      (FRCs).
AB  - Fouling release coatings (FRCs) are today the main environment-friendly
      alternative to traditional self-polishing coatings, that continuously release
      biocides and/or heavy metals into water. FRCs are available on the market as
      environmentally friendly AF paints and most of them do not contain bioactive
      agents, however no complete and reliable assessment of their environmental impact
      has yet been carried out. Only few literature data proving their AF efficacy
      combined with a demonstrated lack of toxicological effects are available.
      Ecotoxicological bioassays are commonly used to predict the potential
      environmental impact of traditional AF paints. Standardized methodologies to
      obtain leaching products from biocide-based paints are available, while few
      studies propose experimental methods to assess the potential effects of biocide
      free FRCs leachates on non-target organisms. The aim of this work is to propose
      an experimental protocol to obtain leaching products from biocide-free FRCs in
      order to evaluate the potential release of substances having toxic effects, by
      means of an ecotoxicological bioassay. Two ecotoxicological end-points with
      different sensitivity levels were considered (multi-end-point approach). Five
      silicone-based commercial coatings were used: their leaching products were
      collected after different immersion times following the developed experimental
      method and then two ecotoxicological end-points were evaluated on II stage
      nauplii of the crustacean Amphibalanus amphitrite as model organism. Moreover,
      chemical analyses were performed on leachates collected after each immersion
      time, focusing on the presence of metals in leaching products. From the results
      obtained from the bioassay, even if not indicative of the real environmental
      impact of FRCs, a release of toxic substances was observed from tested coatings
      during early immersion stages, likely to affect the exposed model organism. The
      potential leaching toxicity of the five tested products was compared. No clear
      correspondence could be identified between the concentrations of metals detected
      in leachates and the obtained ecotoxicological data, thus suggesting that other
      active components might be released by FRCs responsible for the toxic effects
      pointed out on A. amphitrite larvae.

PMID- 30274720
TI  - Ecotoxicological effects of polystyrene microbeads in a battery of marine
      organisms belonging to different trophic levels.
AB  - The aim of this study was to detect ecotoxicological effects of 0.1 MUm
      polystyrene microbeads in marine organisms belonging to different trophic levels.
      MP build up, lethal and sub-lethal responses were investigated in the bacterium
      Vibrio anguillarum (culturability), in the green microalga Dunaliella tertiolecta
      (growth inhibition), in the rotifer Brachionus plicatilis (mortality and swimming
      speed alteration) and in the sea urchin Paracentrotus lividus (immobility and
      swimming speed alteration) exposed to a wide range of microplastic (MP)
      concentrations (from 0.001 to 10 mg L-1). Survival was not affected in all
      organisms up to 10 mg L-1, while algal growth inhibition, rotifer and sea urchin
      larvae swimming behaviour alterations were observed after exposure to MPs.
      Ingestion was only observed in rotifers and it was directly correlated with sub
      lethal effects. These results account for the ecotoxicological risk associated to
      the polystyrene microbeads, which are able to affect different endpoints in
      primary producers and consumers (rotifers and sea urchins) since no effects were
      observed in decomposers. This study points out the importance of using a battery
      of marine organisms belonging to different trophic levels by studying acute
      toxicity of MPs at low and high contamination levels, and investigating sub
      lethal responses. Further investigations aimed at studying the transfer of these
      materials through the web are particularly recommended.

PMID- 30274722
TI  - The Australian National Hand Hygiene Initiative: framework for future research.

PMID- 30274721
TI  - Quality of life changes after stereotactic ablative radiotherapy for liver
      metastases: A prospective cohort analysis.
AB  - PURPOSE: To report the changes in quality of life (QoL) after stereotactic
      ablative radiotherapy (SABR) in patients with liver metastases (LM). MATERIALS
      AND METHODS: A prospective cohort study was undertaken to measure the acute
      changes in QoL after SABR. Patients with 1-3 treated LM were eligible. Doses of
      30-60 Gy in 3-5 fractions were delivered. Prospective QoL was measured using the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaires, Core 15 for Palliative Care (EORTC QLQ-C15-PAL) and liver
      metastases (LM21), at baseline, 1st week and last day of treatment, then 1, 6 and
      12 weeks after SABR. The functional living index-emesis (FLIE) was collected at
      baseline, 1st week, last day and 1 week after treatment. Univariable and
      multivariable linear mixed modeling were performed as appropriate to assess
      changes in QoL over time. RESULTS: Sixty patients were included. The most common
      primary cancer was colorectal (42%). The global health score measured by QLQ-C15
      PAL was significantly worse at treatment completion (p = 0.001), 1 week (p =
      0.003) and 6 weeks (p = 0.002) after SABR but recovered by 12 weeks (p = 0.124).
      Nausea and constipation were worse at treatment completion (p < 0.05) but
      recovered 1 week after while fatigue recovered 6 weeks post-SABR. The majority of
      patients reported stable QoL at 12 weeks for all domains in the C15-PAL and LM21
      questionnaires. CONCLUSION: SABR offers a non-invasive mean of ablating LM with
      minimal impact on acute QoL.

PMID- 30274723
TI  - Effects of the Australian National Hand Hygiene Initiative after 8 years on
      infection control practices, health-care worker education, and clinical outcomes:
      a longitudinal study.
AB  - BACKGROUND: The National Hand Hygiene Initiative (NHHI) is a standardised culture
      change programme based on the WHO My 5 Moments for Hand Hygiene approach to
      improve hand hygiene compliance among Australian health-care workers and reduce
      the risk of health-care-associated infections. We analysed its effectiveness.
      METHODS: In this longitudinal study, we assessed outcomes of the NHHI for the 8
      years after implementation (between Jan 1, 2009, and June 30, 2017), including
      hospital participation, hand hygiene compliance (measured as the proportion of
      observed Moments) three times per year, educational engagement, cost, and
      association with the incidence of health-care-associated Staphylococcus aureus
      bacteraemia (HA-SAB). FINDINGS: Between 2009 and 2017, increases were observed in
      national health-care facility participation (105 hospitals [103 public and two
      private] in 2009 vs 937 hospitals [598 public and 339 private] in 2017) and
      overall hand hygiene compliance (36 213 [63.6%] of 56 978 Moments [95% CI 63.2
      63.9] in 2009 vs 494 673 [84.3%] of 586 559 Moments [84.2-84.4] in 2017;
      p<0.0001). Compliance also increased for each Moment type and for each health
      care worker occupational group, including for medical staff (4377 [50.5%] of 8669
      Moments [95% CI 49.4-51.5] in 2009 vs 53 620 [71.7%] of 74 788 Moments [71.4
      72.0]; p<0.0001). 1 989 713 NHHI online learning credential programmes were
      completed. The 2016 NHHI budget was equivalent to AUD$0.06 per inpatient
      admission nationally. Among Australia's major public hospitals (n=132), improved
      hand hygiene compliance was associated with declines in the incidence of HA-SAB
      (incidence rate ratio 0.85; 95% CI 0.79-0.93; p<=0.0001): for every 10% increase
      in hand hygiene compliance, the incidence of HA-SAB decreased by 15%.
      INTERPRETATION: The NHHI has been associated with significant sustained
      improvement in hand hygiene compliance and a decline in the incidence of HA-SAB.
      Key features include sustained central coordination of a standardised approach
      and incorporation into hospital accreditation standards. The NHHI could be
      emulated in other national culture-change programmes. FUNDING: Australian
      Commission on Safety and Quality in Health Care.

PMID- 30274724
TI  - Where evidence, ethics, and professionalism converge.

PMID- 30274725
TI  - A novel preoperative model to predict 90-day surgical mortality in patients
      considered for renal cell carcinoma surgery.
AB  - INTRODUCTION: Surgical benefits for renal cell carcinoma must be weighed against
      competing causes of mortality, especially in the elderly patient population. We
      used a large cancer registry to evaluate the impact of patient and cancer
      specific factors on 90-day mortality (90DM). A nomogram to predict the odds of
      short-term mortality was created. MATERIALS AND METHODS: The National Cancer
      Database was queried to identify all patients with clinically localized,
      nonmetastatic disease treated with partial or radical nephrectomy. Using a random
      sample of 60%, multiple logistic regression with 90DM outcomes were performed to
      identify preoperative variables associated with mortality. Variables included
      age, sex, race, co-morbidity score, tumor size, and presence of a thrombus. A
      nomogram was created and tested on the remaining 40% of patients to predict 90DM.
      RESULTS: 183,407 patients met inclusion criteria. Overall 90DM for the cohort was
      1.9%. All preoperative variables significantly influenced the risk of 90DM.
      Patient age was by far the strongest predictor. Nomogram scores ranged from 0 to
      12. Compared to patients with 0 to 1 points, those with 2 to 3 (odds ratio [OR]
      2.89, 2.42-3.46; P < 0.001), 4 to 5 (OR 6.25, 5.26-7.43; P < 0.001), and >6 (OR
      12.86, 10.83-15.27; P < 0.001) were at incrementally significantly higher odds of
      90DM. Being >80 years of age alone placed patients into the highest risk of
      surgical mortality. CONCLUSIONS: Management of localized kidney cancer must
      consider competing causes of mortality, especially in elderly patients with
      multiple co-morbidities. We present a preoperative tool to calculate risk of
      surgical short-term mortality to aid surgeon-patient counseling.

PMID- 30274726
TI  - Moving On!: A Transition Program for Promoting Healthy Eating and an Active
      Lifestyle Among Student-Athletes After College.

PMID- 30274727
TI  - Process Evaluation of a Policy, Systems, and Environmental Change Intervention in
      an Urban School District.
AB  - OBJECTIVE: To conduct a comprehensive process evaluation of a policy, systems,
      and environmental (PSE) change intervention. DESIGN: Quasi-experimental, mixed
      methods. SETTING: Low-income urban school district. PARTICIPANTS: Fifth-grade
      students in 4 schools assigned to 2 intervention and 2 comparison schools
      (intervention, n = 142; comparison, n = 170). INTERVENTION: Both groups received
      a nutrition curriculum delivered by classroom teachers. Intervention schools also
      received 10 PSE lessons taught by paraprofessional educators. MAIN OUTCOME
      MEASURES: Quantitative data were obtained from fidelity and observation
      checklists, grading rubrics and self-reported student surveys. Focus group and
      interviews provided qualitative data. Quantitative measures included assessments
      of PSE and fruit and vegetable knowledge, as well as assessment of times fruits
      and vegetables (FV) were consumed yesterday. ANALYSES: Qualitative data were
      analyzed using inductive content analysis. Quantitative data were analyzed using
      repeated measures analysis of variance and analysis of co-variance. RESULTS:
      Fidelity, dose, reach, and acceptance of PSE intervention were high; students
      felt more empowered, although PSE lessons were considered lengthy and
      complicated. Intervention PSE and FV knowledge scores were significantly higher
      than comparison scores (F37.56, P < .001; and F3.94, P < .05, respectively).
      However, issues in communication were identified between school staff and
      researchers. CONCLUSIONS AND IMPLICATIONS: Policy, systems, and environmental
      classroom interventions commented on the differences between quantitative and
      qualitative assessments, and this suggests the need for more sensitive
      quantitative assessments. Future research should look at long-term outcomes as
      this study only looked at short-term outcomes.

PMID- 30274728
TI  - Pyomyositis Diagnosed by Point-of-Care Ultrasound in the Emergency Department.
AB  - BACKGROUND: Currently, the role of ultrasound in diagnosing superficial abscesses
      is well validated, however, its role for deep space infections and intramuscular
      pathology is limited. Distinguishing between simple cellulitis and abscess is
      critical for emergency physicians (EP), as the treatment is very different.
      Management of cellulitis relies on antibiotic therapy, whereas abscess treatment
      requires incision and drainage. It is important that EPs can accurately
      distinguish between the two entities. CASE REPORT: We report a case of a 41-year
      old man with a history of high blood pressure and poorly controlled diabetes who
      presented with right lateral thigh redness, warmth, and tenderness. A point-of
      care ultrasound (POCUS) of the patient's right lateral thigh with a high
      frequency linear (8 MHz) ultrasound probe showed a 2.93 * 3.38 * 6.0-cm complex
      fluid collection deep to the fascial plane, approximately 3.0 cm from the skin
      surface, that contained mixed echogenicities with posterior acoustic enhancement
      consistent with an intramuscular abscess of the vastus lateralis. The patient was
      diagnosed with pyomyositis of his vastus lateralis. He was started on vancomycin
      and admitted to the surgical service for antibiotic treatment and surgical
      drainage. WHY SHOULD EMERGENCY PHYSICIANS BE AWARE OF THIS?: This case
      demonstrates that the use of POCUS by EPs can facilitate the rapid recognition
      and treatment of a disease that is challenging to diagnose on physical
      examination and can be potentially life-threatening if missed. EPs can consider
      performing a POCUS when evaluating skin infections to ensure rapid diagnosis and
      appropriate medical care for a potentially severe condition.

PMID- 30274729
TI  - A Uniquely Abnormal Stool Specimen: A Case Report.
AB  - BACKGROUND: Autoamputation of the appendix is a condition associated with the
      Ladd's procedure, a pediatric surgical technique for correction of intestinal
      malrotation. A 4-year-old male patient with a history of a Ladd's procedure
      performed as a newborn was brought in by his mother for "passing intestine" just
      prior to arrival. She reported that for several weeks her son had intermittent,
      crampy abdominal pain that resolved after the unusual-appearing bowel movement.
      After reviewing an image of the bowel movement, and in consultation with
      pediatric surgery, it was concluded that the patient had passed a devascularized
      appendix in his stool immediately prior to arrival. CASE REPORT: A 4-year-old boy
      with a past medical history of heterotaxy syndrome (inversion of the thoraco
      abdominal organs), a double outlet right ventricle, and Ladd's procedure
      presented to the Emergency Department (ED) after "passing intestine" in his
      stool. Close examination of the photo demonstrated a tubular structure with
      taenia, consistent with an appendix. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE
      OF THIS?: Autoamputation of the appendix is an uncommon presentation in the ED.
      Passing a devascularized appendix is a benign condition and can present with
      weeks of intermittent abdominal pain that resolves with passage of appendix in
      the stool. Remnants of the appendix can remain within the intestinal lumen years
      after the Ladd's procedure. Emergency physicians with a general awareness of this
      rare phenomenon can confidently make the diagnosis and reassure worried parents.

PMID- 30274730
TI  - Febrile Infant with Skin Rash.

PMID- 30274731
TI  - The World Bank Group: Innovative financing for health and opportunities for
      global surgery.
AB  - The World Bank Group is the largest global development organization working to
      end poverty and promote shared prosperity. Its 5 institutions play an essential
      role in the advancement of global health through innovative health financing,
      data collection and management, policy reform, and advocacy. Previously, the
      World Bank Group has supported global surgery through data collection and
      advocacy. As it grows, it must continue to focus on the importance of surgical
      care in promoting health and avoiding poverty in low- and middle-income
      countries. The house of surgery and its community should play an active role in
      advocating for the many ways in which the World Bank Group could facilitate the
      strengthening of surgical systems to improve access to surgical care worldwide.

PMID- 30274732
TI  - High-dose radioactive iodine therapy is associated with decreased risk of
      recurrence in high-risk papillary thyroid cancer.
AB  - OBJECTIVES: We aimed to determine the effect of adjuvant radioactive iodine dose
      on recurrence rate in high-risk papillary thyroid cancer. METHODS: More than
      1,500 patients treated for papillary thyroid cancer at high-volume centers in
      France and the United States from 2004-2014 were reviewed. Patients considered at
      high risk for recurrence per the 2015 American Thyroid Association guidelines
      were analyzed and grouped by initial radioactive iodine dose: intermediate
      (median 100 mCi) or high dose (median 150 mCi). Propensity score matching was
      performed to control for baseline characteristics. RESULTS: In a propensity
      matched cohort of 66 patient pairs, there were equivalent rates of gross
      extrathyroidal extension (71% vs 71%, P = 1.00), positive margins (55% vs 55%, P
      = 1.00), lymph node metastases >= 3 cm (9% vs 9%, P = 1.00), extranodal extension
      (32% vs 33%, P = .85), and distant metastases (2% vs 5%, P = .31). Over a median
      follow-up of 4.5 years (interquartile ratio 2.0-7.5 years), the intermediate-dose
      radioactive iodine group had a significantly higher rate of recurrence than
      patients in the high-dose radioactive iodine group: 24 out of 66 (36%) vs 13 out
      of 66 (20%), P = .03. CONCLUSION: High-dose radioactive iodine is associated with
      lower recurrence rate compared with intermediate-dose radioactive iodine for
      patients with American Thyroid Association high-risk papillary thyroid cancer.

PMID- 30274733
TI  - Heterogeneous and low-intensity parathyroid autofluorescence: Patterns suggesting
      hyperfunction at parathyroid exploration.
AB  - BACKGROUND: Although parathyroid glands have been found to exhibit
      autofluorescence with near-infrared fluorescence imaging, it is unknown if
      autofluorescence characteristics vary between hyperfunctioning and
      normofunctioning glands. The hypothesis was that pattern of autofluorescence
      exhibited by hyperfunctioning versus normofunctioning parathyroid glands would be
      different. METHODS: This is an Institutional Review Board-approved, prospective
      clinical study. Patients underwent bilateral neck exploration for primary
      hyperparathyroidism, during which autofluorescence from each gland was assessed
      with near-infrared fluorescence imaging. Pattern and intensity of
      autofluorescence between hyperfunctioning and normofunctioning parathyroid glands
      were compared. RESULTS: Overall, 199 parathyroid glands were identified in 50
      patients (single gland disease, n = 31; multigland disease, n = 19).
      Autofluorescence was detected from 96% (n = 192) of parathyroid glands, all of
      which exhibited a higher intensity autofluorescence than the background tissues.
      Parathyroid gland location was revealed by near-infrared fluorescence imaging
      before dissection in 26% (n = 52). A total of 77 glands that were large or firm
      were excised and 122 were preserved because of normal appearance.
      Hyperfunctioning parathyroid glands had a lower mean normalized autofluorescence
      intensity than normofunctioning parathyroid glands (1.8, and 2.6, respectively, P
      < .001). Moreover, hyperfunctioning parathyroid glands more often exhibited a
      heterogeneous pattern of autofluorescence (75% and 5%, respectively, P < .001).
      On multivariate analysis, only parathyroid gland hyperfunction correlated with
      normalized autofluorescence intensity. On receiver operative characteristic
      curve, optimal cutoff of normalized autofluorescence intensity to differentiate
      hyperfunctioning from normofunctioning parathyroid glands was 2.0. CONCLUSION:
      Our results indicate that hyperfunctioning and normofunctioning parathyroid
      glands exhibit different patterns of autofluorescence in hyperparathyroidism.
      Given these findings, autofluorescence pattern could be implemented as another
      adjunctive parameter for gland assessment during parathyroid exploration.

PMID- 30274734
TI  - Delayed bone healing by collagen membrane in early phase of 4 weeks.
AB  - OBJECTIVE: Barrier membranes are important in maintaining space in guided bone
      regeneration process by preventing downgrowth of epithelial or connective tissue.
      In this study, the effects of resorbable membranes during the early stages of
      bone regeneration in rats with impaired bone healing capacity were investigated.
      STUDY DESIGN: Twenty-eight rats were selected for this study. Half of the animals
      were selected for radiation therapy before surgical procedure (G3, G4). Animals
      were assigned into 4 groups (G1-G4). A circular defect was created in the central
      parietal bone. It was covered with resorbable membrane in G2 and G4. After 4
      weeks, the animals were sacrificed. RESULTS: At week 4, the new bone formation
      was observed around the margin of old bone in G1, G2 and G4 groups. Osteoclast
      was most abundant in the G1 group (18.3 +/- 7.7) and least abundant in the G4
      group (7.9 +/- 4.7). The mean of osteocalcin levels in blood was the highest in
      the G2 group and lowest in the G3 group. Only G4 group showed significant
      difference in Runx2 levels between before-treatment and after- treatment.
      CONCLUSIONS: Bone healing is adversely affected after radiation therapy. In
      addition, resorbable membranes can delay healing in the early stages of bone
      regeneration.

PMID- 30274735
TI  - How to Manage Heart Failure: New Guidelines 2018.

PMID- 30274736
TI  - Directed Evolution of Adeno-Associated Virus Vectors in Human Cardiomyocytes for
      Cardiac Gene Therapy.

PMID- 30274737
TI  - Personalized stent design for congenital heart defects using pulsatile blood flow
      simulations.
AB  - Stent size selection and placement are among the most challenging tasks in the
      treatment of pulmonary artery stenosis in congenital heart defects (CHD). Patient
      specific 3D model from CT or MR improves the understanding of the patient's
      anatomy and information about the hemodynamics aid in patient risk assessment and
      treatment planning. This work presents a new approach for personalized stent
      design in pulmonary artery interventions combining personalized patient geometry
      and hemodynamic simulations. First, the stent position is initialized using a
      geometric approach. Second, the stent and artery expansion, including the
      foreshortening behavior of the stent is simulated. Two stent designs are
      considered, a regular stent and a Y-stent for bifurcations. Computational fluid
      dynamics (CFD) simulations of the blood flow in the initial and expanded artery
      models are performed using patient-specific boundary conditions in form of a
      pulsatile inflow waveform, 3-element Windkessel outflow conditions, and
      deformable vessel walls. The simulations have been applied to 16 patient cases
      with a large variability of anatomies. Finally, the simulations have been
      clinically validated using retrospective imaging from angiography and pressure
      measurements. The simulated pressure, volume flow and flow velocity values were
      on the same order of magnitude as the reference values obtained from clinical
      measurements, and the simulated stent placement showed a positive impact on the
      hemodynamic values. Simulation of geometric changes combined with CFD simulations
      offers the possibility to optimize stent type, size, and position by evaluating
      different configurations before the intervention, and eventually allow to test
      customized stent geometries and new deployment techniques in CHD.

PMID- 30274738
TI  - Burden of cytomegalovirus disease in allogeneic hematopoietic cell transplant
      recipients: a national, matched cohort study in an inpatient setting.
AB  - PURPOSE OF THE STUDY: No studies have compared the risk of mortality or graft
      versus-host disease, in an inpatient setting in France, in allogeneic
      hematopoietic cell transplant recipients who develop cytomegalovirus disease with
      those who do not. This study assessed the impact of cytomegalovirus disease on
      clinical outcomes and healthcare resource utilization in allogeneic hematopoietic
      cell transplant recipients using the French Programme de Medicalisation des
      Systemes d'Information database. PATIENTS AND METHODS: Recipients who had
      undergone allogeneic hematopoietic cell transplant in French hospitals between
      2008 and 2011 were included in this retrospective, matched cohort study. Those
      with cytomegalovirus disease were each matched with two allogeneic hematopoietic
      cell transplant recipients without cytomegalovirus disease according to
      demographic and clinical characteristics. Probabilities of in-hospital mortality,
      graft rejection and/or graft-versus-host disease, and healthcare resource
      utilization were compared up to 12 months after cytomegalovirus disease
      diagnosis. RESULTS: Overall, 4884 transplant recipients were enrolled, of which
      194 had cytomegalovirus disease. Of these, 165 recipients with cytomegalovirus
      disease were matched to 330 without cytomegalovirus disease (1:2 ratio). The
      development of cytomegalovirus disease was associated with a significantly higher
      risk of in-hospital mortality (relative risk = 1.7, p = 0.0005) and higher
      cumulative number of inpatient days (p < 0.0001), but was not associated with a
      significantly higher risk of graft rejection and/or graft-versus-host disease or
      healthcare costs. CONCLUSIONS: Due to the increased risk of in-hospital mortality
      and higher cumulative number of inpatient days in allogeneic hematopoietic cell
      transplant recipients with cytomegalovirus disease versus those without, new
      strategies to prevent and manage cytomegalovirus disease are warranted.

PMID- 30274739
TI  - Content and accuracy of nutrition-related posts in bariatric surgery Facebook
      support groups.
AB  - BACKGROUND: Support after bariatric surgery is critical. Access to bariatric
      support groups is sometimes challenging, leading people to seek support on social
      media platforms like Facebook. Given the ubiquity of recommendations solicited
      and provided on Facebook regarding nutrition and bariatric surgery, understanding
      the content and accuracy of these posts is important. OBJECTIVES: The primary aim
      of the present study was to describe the content of nutrition-related information
      sought on bariatric Facebook support groups/pages. A secondary aim was to
      evaluate the accuracy of this content. SETTING: Integrated multispecialty health
      system. METHODS: An iterative content analysis process was conducted and resulted
      in identification of 8 primary coding themes. Additionally, 3 registered
      dieticians with extensive experience in bariatric surgery and obesity treatment
      examined posts that provided nutritional recommendations to determine accuracy.
      RESULTS: Members most commonly sought advice regarding products and practices to
      assist in achieving nutritional guidelines (35%). Over half of the posts
      contained inaccurate content or information that was too ambiguous to determine
      accuracy; 7% of posts were found to be inaccurate or inconsistent with American
      Society for Metabolic and Bariatric Surgery nutrition guidelines and expert
      registered dietician opinions, 22% of posts were found to contain both accurate
      and inaccurate information, and 24% of posts were considered too ambiguous and
      required more context to determine the accuracy. CONCLUSIONS: Results highlight
      the need for bariatric programs to provide greater nutrition education support to
      patients postoperatively and to provide caution about the inconsistent nature of
      some nutrition-related content found on Facebook bariatric support groups.

PMID- 30274740
TI  - Postoperative outcomes based on patient participation in a presurgery education
      and weight management program.
AB  - BACKGROUND: The benefits of presurgery weight management programs (WMPs) for
      bariatric patients are mixed; some show a positive impact on percent excess
      weight loss (%EWL) at 12 months postsurgery, while others show no effect.
      OBJECTIVES: The purpose of this study was to compare pre- and postoperative 6-
      and 12-month outcomes between patients who attended a 12-week presurgery WMP and
      patients who did not participate. SETTING: Ohio State Wexner Medical Center,
      University Hospital, United States. METHODS: A retrospective medical record
      analysis was conducted to compare preoperative and 6- and 12-month postoperative
      outcomes for patients who attend the presurgery WMP (n = 56) and patients who did
      not (n = 441) within a 2-year time period (N = 497). Descriptive statistics and
      independent t tests were conducted to determine mean differences between groups,
      while controlling for surgery type, for weight status outcomes (%EWL, change in
      body mass index) preoperatively and 6 and 12 months postsurgery, and length of
      stay and readmission rate. RESULTS: Patients who attended the preoperative WMP
      had significantly higher %EWL at 12 months postsurgery compared with patients who
      did not attend the WMP. Additional findings indicated a positive, but
      nonsignificant effect, from the WMP on presurgery body mass index, and
      postsurgery %EWL at 6 months and body mass index change at 6 and 12 months
      postsurgery. CONCLUSIONS: Patients attending the WMP had better 12-month %EWL and
      outcomes compared with those who did not attend the WMP, though this was not true
      for 6-month outcomes and differed based on surgery type.

PMID- 30274741
TI  - Cocaine and amphetamine regulated transcript and brain-derived neurotrophic
      factor in morbid obesity. One-year follow-up after gastric bypass.
AB  - BACKGROUND: The identification of biomarkers associated with obesity and response
      to treatment could represent an important advance to design more effective and
      personalized therapeutic strategies. The complexity of morbid obesity could be
      explained as the combination of genetic, biochemical, cultural, and behavioral
      factors, among others. The study of biomarkers should be considered a determinant
      factor taken into account in this equation. OBJECTIVES: The aim of this study was
      to define better biomarker profiles potentially associated to the short-term
      outcome of bariatric surgery by paying attention to cocaine and amphetamine
      regulated transcript and brain-derived neurotrophic factor, 2 neuropeptides
      related to eating behavior. SETTING: University General Hospital of Ciudad Real,
      Spain. METHODS: Twenty-seven morbidly obese patients and 30 healthy weight
      individuals matched by age and sex were selected for the study. RESULTS: Patients
      underwent bariatric surgery by Roux-en-Y gastric bypass and responded adequately
      in terms of weight loss and normalization of many biochemical parameters 1 year
      postsurgery. A multivariate analysis showed that the hormonal/neuropeptidic
      profile explained 82% of the variability of the weight loss response. The
      evolution of cocaine and amphetamine regulated transcript paralleled that of
      insulin and leptin, serum levels of this peptide were initially elevated in
      patients (4.24 +/- .47 ng/mL) with respect to controls (2.94 +/- .2 ng/mL), but
      this difference disappeared 1 year after Roux-en-Y gastric bypass (3.14 +/- .26
      ng/mL). Brain-derived neurotrophic factor levels were also decreased by Roux-en-Y
      gastric bypass (11.93 +/- .96 ng/mL postsurgery versus 15.3 +/- 1.02 ng/mL
      presurgery), even when this peptide was not elevated in patients before surgery
      (14.23 +/- .86 ng/mL in controls). CONCLUSIONS: The results suggest that cocaine
      and amphetamine regulated transcript and brain-derived neurotrophic factor could
      be envisaged as new candidate biomarkers of short-term outcome after surgery.

PMID- 30274742
TI  - Proteomic profile of sex-sorted bull sperm evaluated by SWATH-MS analysis.
AB  - The identification of distinct proteins present on the membrane of spermatozoa
      with X and Y chromosomes allows the development of immuno-sexing techniques. The
      aim of this study, therefore, was to use mass spectrometry to analyze the protein
      profile of sperm previously categorized using flow cytometry into X or Y-bearing
      semen pools. Sex-sorted sperm samples (n = 6 X and n = 6 Y) were used. Proteins
      were extracted and analyzed by mass spectrometry using data independent
      acquisition (DIA). The data were searched against taxonomy Bos taurus in the
      Swiss Prot database. In total, 459 protein groups were identified. Of these,
      eight proteins were in differential abundances between the X- and Y-bearing sperm
      population. Among the major proteinsdetected, EF-hand domain-containing protein
      1, a protein involved in embryonic development, is more abundant in Y-bearing
      spermatozoa. In addition, proteins FUN14, domain-containing protein 2, NADH
      dehydrogenase [ubiquinone] iron-sulfur protein 7 mitochondrial, cytochrome C
      oxidase subunit 2, acetyl -CoA carboxylase type beta were more abundant in X
      bearing sperm. In conclusion, there were differences in abundance of proteins
      between X- and Y-bearing bull spermatozoa. This fact, may contribute to future
      studies related to sperm physiology and possibility development of immuno-sexing
      techniques.

PMID- 30274743
TI  - Theoretical studies of the pyranose ring under mechanical stress.
AB  - In this work we use our Enforced Geometry Optimization (EGO) method to
      investigate conformational transitions in the pyranose ring under mechanical
      stress caused by external forces. We examine possible transitions and/or
      inversions induced by external forces in the pyranose ring in the chair
      conformation with two axial glycosidic bonds. The results obtained provide new
      insight into the mechanism of the conformational transitions which strongly
      depends on substituents present in a pyranose ring. We also conclude that
      interpretation of AFM force-extension curves is not necessarily straightforward;
      not every plateau there corresponds to a conformational transition and not every
      transition can be clearly seen as a plateau.

PMID- 30274744
TI  - Determining the likelihood that fatigue was present in a road accident: A
      theoretical review and suggested accident taxonomy.
AB  - Estimates in developed countries of the extent to which fatigue contributes to
      road accidents range from as low as 5% to as high as 50% of all accidents.
      Compared with other causes of road accidents (e.g., speeding, drink-driving), the
      variability in these estimates is exceptionally high and may be indicative of the
      difficulty in determining the likelihood of fatigue as a cause of road accidents.
      This review compares differences in the way road accidents are classified as
      fatigue-related (or not) by expert panels and road safety regulators,
      highlighting conflicting conceptual approaches, lack of consistency, and the poor
      psychometric qualities of classification rules used across jurisdictions. In
      order to facilitate future research, the review then proposes a new theoretical
      approach and a potentially more logical accident 'taxonomy'. A putative accident
      'taxonomy' is proposed using two dimensions: (1) estimating the likelihood that a
      driver was fatigued at the time of the accident, and (2) estimating the degree to
      which accident phenomenology is consistent with fatigue-related error. This
      'taxonomy' could assist accident investigators and road safety regulators to more
      reliably quantify the contribution of fatigue to road accidents, and may also
      assist researchers and regulators in the post-hoc interrogation of existing
      accident databases to better determine the relative incidence of fatigue-related
      road accidents.

PMID- 30274745
TI  - Response to letter to editor "Optical coherence tomography (OCT) findings in
      obstructive sleep apnea" by Piotr Kanclerz.

PMID- 30274746
TI  - Optical coherence tomography (OCT) findings in obstructive sleep apnea.

PMID- 30274747
TI  - [Participatory tools and methods for community action. SESPAS Report 2018].
AB  - Participation is a process that requires the involvement of the policy makers,
      managers, technicians and staff of the institutions, and of citizens, as well as
      intersectoral and interdisciplinary action. To generate transformative changes,
      an infrastructure that encourages participation and planned action is required,
      and that recognises all the actors in the process. It takes time and commitment
      to ensure continuity through the joint production of actions, hence the
      importance of consolidating participatory projects that continue beyond political
      changes making public services sustainable. Training, the appropriate use of
      participation tools and a horizontal policy of delegated power are essential to
      ensure participation. Surveys, sociograms, flowcharts, health assets mapping,
      participatory budgets and participatory evaluation matrices are some of the tools
      that can be chosen, depending on the type of subjects addressed, the time and
      resources available, the characteristics of the participating population and
      territory, as well as determining the use that will be made of the information
      generated for the next phase. Participation tools are useful for citizens and
      professionals to analyze, understand, debate and decide collectively how to
      improve living conditions and environments. Over the past decade, social networks
      in the virtual environment have generated new trends in mass participation, which
      are self-managed by citizens.

PMID- 30274748
TI  - Finding the right balance.

PMID- 30274749
TI  - Microvascular obstruction in non-STEMI related areas: An uninvited guest in
      STEMI?

PMID- 30274750
TI  - Incremental diagnostic and prognostic value of the QRS-T angle, a 12-lead ECG
      marker quantifying heterogeneity of depolarization and repolarization, in
      patients with suspected non-ST-elevation myocardial infarction.
AB  - BACKGROUND: The value of the 12-lead ECG in the diagnosis of non-ST-elevation
      myocardial infarction (NSTEMI) is limited due to insufficient sensitivity and
      specificity of standard ECG criteria. The QRS-T angle reflects depolarization
      repolarization heterogeneity and might assist in detecting patients with a NSTEMI
      (diagnosis) as well as predicting patients with an increased mortality risk
      (prognosis). METHODS: We prospectively enrolled 2705 consecutive patients with
      symptoms suggestive of NSTEMI. The QRS-T angle was automatically derived from the
      standard 10 s 12-lead ECG recorded at presentation to the ED. Patients were
      followed up for all-cause mortality for 2 years. RESULTS: NSTEMI was the final
      diagnosis in 15% (n = 412) of patients. QRS-T angles were significantly greater
      in patients with NSTEMI compared to those without (p < 0.001). The use of the QRS
      T angle in addition to standard ECG criteria indicative of ischemia improved the
      diagnostic accuracy for NSTEMI as quantified by the area under the ROC curve from
      0.68 to 0.72 (p < 0.001). An algorithm for the combined use of standard ECG
      criteria and the QRS-T angle improved the sensitivity of the ECG for NSTEMI from
      45% to 78% and the specificity from 86% to 91% (p < 0.001 for both comparisons).
      The 2-year survival rates were 98%, 97% and 87% according to QRS-T angle tertiles
      (p < 0.001). CONCLUSION: In patients with suspected NSTEMI, the QRS-T angle
      derived from the standard 12-lead ECG provides incremental diagnostic accuracy on
      top of standard ECG criteria indicative of ischemia, and independently predicts
      all-cause mortality during 2 years of follow-up.

PMID- 30274751
TI  - Can computer assisted analysis of a standard 12-lead ECG be used for early
      diagnosis and monitoring of disease progression in pulmonary hypertension?

PMID- 30274752
TI  - Dynamic severe mitral regurgitation on hospital arrival as prognostic predictor
      in patients hospitalized for acute decompensated heart failure.
AB  - BACKGROUND: Severe mitral regurgitation (MR) on hospital arrival at the onset of
      acute decompensated heart failure (ADHF) can improve after ADHF treatment because
      MR is dynamic in nature. This study investigated the clinical significance of the
      dynamic severe MR on hospital arrival in ADHF patients. METHODS: Transthoracic
      echocardiography was performed on 784 patients hospitalized for ADHF both on
      arrival and after ADHF treatment, of whom 563 with at least mild MR after ADHF
      treatment were enrolled and divided into 3 groups based on the MR severity:
      severe at both times (persistent MR, n = 106); severe on arrival and improved to
      mild/moderate after ADHF treatment (dynamic MR, n = 149); and mild/moderate at
      both times (non-significant MR, n = 308). The primary outcome measure was defined
      as a composite of cardiac death, rehospitalization for heart failure, and mitral
      valve intervention within 1-year. RESULTS: The incidence of the primary outcome
      measure in the dynamic MR group (44.8%) was significantly higher than that in the
      non-significant MR group (22.1%, adjusted hazard ratio [HR]: 0.50, 95% confidence
      interval [CI]: 0.34-0.73, P < 0.001), and similar to that in the persistent MR
      group (44.4%, adjusted HR: 1.08, 95% CI: 0.69-1.67, P = 0.75). The risk of
      dynamic MR was consistent in the subgroups of patients with reduced (<45%) and
      preserved left ventricular ejection fraction (Pinteraction = 0.56). CONCLUSIONS:
      In patients hospitalized for ADHF, dynamic severe MR on hospital arrival was
      associated with poorer outcomes than non-significant MR and had similar risk to
      persistent severe MR. Acute dynamic MR is a potential therapeutic target in ADHF
      patients.

PMID- 30274753
TI  - Impact of vascular access on the development of contrast induced nephropathy in
      patients undergoing coronary angiography and/or percutaneous coronary
      intervention.
AB  - BACKGROUND: Contrast induced nephropathy (CIN) is a common complication of
      procedures that foresee the use of contrast media. Several risk factors have been
      identified as independent predictors of CIN, but, to date, no definitive data are
      available about the association between the angiographic approach and its
      development. METHODS AND RESULTS: Our population included 4199 patients
      undergoing coronary angiography and/or PCI. CIN was defined as an absolute >=0.5
      mg/dl or a relative >=25% increase in creatinine level at 24-48 h after the
      procedure without another clear cause for the acute kidney injury. The total
      incidence of CIN was 12.4%. We divided our population into two groups, according
      to the angiographic approach: transradial (TR) n = 1915 or transfemoral (TF) n =
      2284. Patients treated with TR approach were more often males, with history of
      hypertension, and PCI, but less often diabetic, with previous myocardial
      infarction, coronary artery by-pass graft surgery and cerebrovascular accident.
      They had a higher ejection fraction, higher prevalence of PCI, elective
      indication but interestingly a lower amount of contrast volume. Patients treated
      with TR approach had higher platelets, Total, LDL and HDL cholesterol, but lower
      triglycerides, glycaemia and basal creatinine. No significant difference was
      observed between the two groups regarding the development of CIN (TR 13.2% vs TF
      11.7%, p = 0.16). The absence of association between angiographic approach and
      the incidence of CIN was also confirmed at multivariate analysis after correction
      for baseline confounders (Adjusted OR [95% CI] = 1.2 [0.97-1.50], p = 0.09) and
      at subgroup analysis according to main risk factors for CIN. Similar results were
      obtained dividing our population according to propensity score tertiles: 1st
      Tertile CIN (TF 8.8% vs TR 8.9%), p = 0.95; OR (99% CI) = 1.01 (0.96-1.48), p =
      0.95, 2nd Tertile CIN (TF 10.8% vs TR 12.4%), p = 0.35; OR (99% CI) = 1.17 (0.84
      1.62), p = 0.35, and 3rd Tertile CIN (TF 15.6% vs TR 17.2%), p = 0.41; OR (99%
      CI) = 1.12 (0.85-1.48), p = 0.41. CONCLUSION: This is the first large study
      showing the absence of relationship between the angiographic access and the
      incidence of CIN.

PMID- 30274754
TI  - Frailty predicts mortality and complications in chronologically young patients
      with traumatic orthopaedic injuries.
AB  - BACKGROUND: As morbidity and mortality from traumatic orthopaedic injuries
      continues to rise, increased research is being conducted on how to best predict
      complications in at risk patients. Recently, frailty indices have been validated
      in a variety of surgical subspecialties as predictors of morbidity and mortality.
      However, the vast majority of research has been conducted on geriatric patient
      populations, with little evidence on patients who are chronologically young. The
      purpose of this study was to evaluate the role of a modified frailty index (mFI)
      in predicting mortality and complications after pelvis, acetabulum, and lower
      extremity trauma in patients of all ages. METHODS: The American College of
      Surgeons National Surgical Quality Improvement Program (NSQIP) database was
      queried from 2005 to 2014 for all patients who underwent surgery for pelvis,
      acetabulum, and lower extremity trauma. The sample size was divided into
      geriatric (age >= 60) and young (age < 60) cohorts. The mFI score was calculated
      for each patient. Bivariate analysis was performed using logistic regression and
      a chi-square test to determine the relationship between mFI and both primary and
      secondary outcomes while adjusting for age. Univariate analysis and multivariate
      analyses were performed. All analyses were done using SAS 9.4 (Cary, NC) and a p
      < 0.05 was considered significant. RESULTS: 56,241 patients were identified to
      have undergone surgery for pelvis, acetabulum, or lower extremity trauma. 28% of
      patients were identified under the age of 60. In the young cohort, mFI was a
      strong predictor of thirty-day mortality (OR 11.02, 95% CI 6.26-19.39, p <
      0.001). With regards to Clavien-Dindo grade IV complications, MFI is also a
      strong predictor in the young cohort (OR 28.82, 95% CI 16.05-51.77, p < 0.001).
      CONCLUSION AND RELEVANCE: The mFI score was a significant predictor of morbidity
      and mortality in chronologically young orthopaedic trauma patients. The use of
      the mFI score can provide an individualized risk assessment to interdisciplinary
      teams for perioperative counseling and to improve outcomes.

PMID- 30274756
TI  - Fascia-iliaca compartment block vs intra-articular hip injection for preoperative
      pain management in intracapsular hip fractures: A blind, randomized, controlled
      trial.
AB  - BACKGROUND: The aim of this study was to compare the fascia-iliaca compartment
      block and the intra-articular hip injection in terms of pain management and the
      need for additional systemic analgesia in the preoperative phase of intracapsular
      hip fractures. METHODS: Patients >65 years old with an intracapsular hip fracture
      were randomized in this prospective, blind, controlled, parallel trial in a Level
      I trauma center. Patients were randomly assigned to receive either the fascia
      iliaca compartment block (cohort FICB) or the intra-articular hip injection
      (cohort IAHI) upon admission to the emergency department. The primary outcome was
      pain relief at 20 min, 12 h, 24 h and 48 h after the regional anesthesia, both at
      rest and during internal rotation of the fractured limb. The Numeric Rating Scale
      was used. Residual pain was managed with the same protocol in all patients.
      Additional analgesic drug administration during the 48 h from admission was
      recorded. RESULTS: A total of 120 patients with comparable baseline
      characteristics were analyzed in this study: the FICB group consisted of 70
      subjects, while the IAHI group consisted of 50 subjects. Pain was significantly
      lower in the IAHI group during movement of the fractured limb at 20 min (p <
      0.05), 12 h (p < 0.05), 24 h (p < 0.05) and 48 h (p < 0.05). In the FICB cohort
      72.9% of patients needed to take oxycodone, in contrast to 28.6% of the IAHI
      cohort (p < 0.05). In the FICB cohort 14.09 +/- 11.57 mg of oxycodone was
      administered, while in the IAHI cohort 4.38 +/- 7.63 mg (p < 0.05). No adverse
      events related to either technique were recorded. CONCLUSIONS: Intra-articular
      hip injection provides better pre-operatory pain management in elder patients
      with intracapsular hip fractures compared to the fascia-iliaca compartment block.
      It also reduced the need for supplementary systemic analgesia. LEVEL OF EVIDENCE:
      Therapeutic Level I.

PMID- 30274757
TI  - External benchmarking of trauma services in New South Wales: Risk-adjusted
      mortality after moderate to severe injury from 2012 to 2016.
AB  - BACKGROUND: Trauma centres and systems have been associated with improved
      morbidity and mortality after injury. However, variability in outcomes across
      centres within a given system have been demonstrated. Performance improvement
      initiatives, that utilize external benchmarking as the backbone, have
      demonstrated system-wide improvements in outcomes. This data driven approach has
      been lacking in Australia to date. Recent improvement in local data quality may
      provide the opportunity to engage in data driven performance improvement. Our
      objective was to generate risk-adjusted outcomes for the purpose of external
      benchmarking of trauma services in New South Wales (NSW) based on existing data
      standards. METHODS: Retrospective cohort study of the NSW Trauma Registry. We
      included adults (>16 years), with an Injury Severity Score >12, that received
      definitive care at either Major Trauma Services (MTS) or Regional Trauma Services
      (RTS) between 2012-2016. Hierarchical logistic regression models were then used
      to generate risk-adjusted outcomes. Our outcome measure was in-hospital death.
      Demographics, vital signs, transfer status, survival risk ratios, and injury
      characteristics were included as fixed-effects. Median odds ratios (MOR) and
      centre-specific odds ratios with 95% confidence intervals were generated. Centre
      level variables were explored as sources of variability in outcomes. RESULTS:
      14,452 patients received definitive care at one of seven MTS (n = 12,547) or ten
      RTS (n = 1905). Unadjusted mortality was lower at MTS (9.4%) compared to RTS
      (11.2%). After adjusting for case-mix, the MOR was 1.33, suggesting that the odds
      of death was 1.33-fold greater if a patient was admitted to a randomly selected
      centre with worse as opposed to better risk-adjusted mortality. Definitive care
      at an MTS was associated with a 41% lower likelihood of death compared to
      definitive care at an RTS (OR 0.59 95%CI 0.35-0.97). Similar findings were
      present in the elderly and isolated severe brain injury subgroups. CONCLUSIONS:
      The NSW trauma system exhibited variability in risk-adjusted outcomes that did
      not appear to be explained by case-mix. A better understanding of the drivers of
      the described variation in outcomes is crucial to design targeted locally
      relevant quality improvement interventions.

PMID- 30274755
TI  - Open abdomen and entero-atmospheric fistulae: An interim analysis from the
      International Register of Open Abdomen (IROA).
AB  - INTRODUCTION: No definitive data describing associations between cases of Open
      Abdomen (OA) and Entero-atmospheric fistulae (EAF) exist. The World Society of
      Emergency Surgery (WSES) and the Panamerican Trauma Society (PTS) thus analyzed
      the International Register of Open Abdomen (IROA) to assess this question.
      MATERIAL AND METHODS: A prospective analysis of adult patients enrolled in the
      IROA. RESULTS: Among 649 adult patients with OA 58 (8.9%) developed EAF.
      Indications for OA were peritonitis (51.2%) and traumatic-injury (16.8%). The
      most frequently utilized temporary abdominal closure techniques were Commercial
      NPWT (46.8%) and Bogota-bag (21.9%). Mean OA days were 7.9 +/- 18.22. Overall
      mortality rate was 29.7%, with EAF having no impact on mortality. Multivariate
      analysis associated cancer (p = 0.018), days of OA (p = 0.003) and time to
      provision-of-nutrition (p = 0.016) with EAF occurrence. CONCLUSION: Entero
      atmospheric fistulas are influenced by the duration of open abdomen treatment and
      by the nutritional status of the patient. Peritonitis, intestinal anastomosis,
      negative pressure and oral or enteral nutrition were not risk factors for EAF
      during OA treatment.

PMID- 30274758
TI  - Can they stop the bleed? Evaluation of tourniquet application by individuals with
      varying levels of prior self-reported training.
AB  - BACKGROUND: Application of extremity tourniquets is a central tenet of multiple
      national initiatives to empower laypersons to provide hemorrhage control (HC).
      However, the efficacy of the general population who self-report prior first-aid
      (FA) or HC training on individual's ability to control bleeding with a tourniquet
      remains unknown. Therefore, the objective of this study was to assess the
      effectiveness of laypeople with self-reported prior FA or HC training to control
      bleeding with a tourniquet. STUDY DESIGN: Employees of a stadium were assessed
      via simulation in their ability to apply a Combat Application Tourniquet. As a
      subgroup analysis of a larger study, participants who self-reported: 1) No prior
      training, 2) FA training only or 2) FA + HC training were compared. Logistic
      regression adjusting for age, gender, education, willingness-to-assist, and
      comfort level in HC was performed. RESULTS: 317 participants were included.
      Compared to participants with no prior training (14.4%,n = 16/111), those with FA
      training only (25.2%,n = 35/139) had a 2.12-higher odds (95%CI:1.07-4.18) of
      correct tourniquet application while those with FA + HC (35.8%,n = 24/67) had a
      3.50-higher odds (95%CI:1.59-7.72) of correct application. Participants with
      prior FA + HC were more willing-to-assist and comfortable performing HC than
      those without prior training (p < 0.05). However, reporting being very willing-to
      assist [OR0.83,95%CI:0.43-1.60] or very comfortable [OR1.11,95%CI:0.55-2.25] was
      not associated with correct tourniquet application. CONCLUSION: Self-reported
      prior FA + HC training, while associated with increased likelihood to correctly
      apply a tourniquet, results in only 1/3 of individuals correctly performing the
      skill. As work continues in empowering and training laypeople to act as immediate
      responders, these findings highlight the importance of effective layperson
      education techniques.

PMID- 30274759
TI  - Hip fractures in the oldest old. Comparative study of centenarians and
      nonagenarians and mortality risk factors.
AB  - INTRODUCTION: Centenarians and nonagenarians constitute a rapidly growing age
      group in Western countries and they are expected to be admitted to hospital with
      hip fractures. The aim of this study was to compare outcomes of centenarian and
      nonagenarian patients following a hip fracture and to identify risk factors
      related to in-hospital and post-discharge mortality in both groups. PATIENTS AND
      METHODS: A prospective evaluation of centenarian patients and nonagenarian
      controls admitted to a tertiary university hospital in Barcelona with hip
      fractures over a period of 5 years and 9 months. Baseline characteristics and
      outcomes in both patient groups were compared. Variables associated with in
      hospital, 30-day, 3-month and 1-year mortality were also analyzed. RESULTS:
      Thirty-three centenarians and 82 nonagenarians were included. The most relevant
      statistically significant differences found were: Barthel index at admission
      (61.90 vs. 75.22), number of drugs before admission (4.21vs 5.55), in-hospital
      complication rates (97 vs. 78%), readmissions at 3 months and 1 year (0 vs 11.7%
      and 3.4 vs. 19.5% respectively) and mortality at 3 months and 1 year (41.4 vs.
      20.8% and 62.1 vs. 29.9%, respectively). Mean number of complications, rapid
      atrial fibrillation, mean age, and urinary tract infection were risk factors
      associated with mortality. CONCLUSIONS: Centenarian patients had similar in
      hospital outcomes to nonagenarians, but experienced more complications and twice
      the 3-month and 1-year mortality rate. The mean number of complications was the
      risk factor most consistently related to in-hospital and post-discharge
      mortality. These findings emphasize the need to improve care in very old patients
      to prevent complications.

PMID- 30274760
TI  - Peri-mortem caesarean section after traumatic arrest: Crisis resource management.
AB  - Peri-mortem caesarean section (PMCS) is a very rare procedure performed to
      improve the chances of survival for both mother and fetus following
      cardiorespiratory arrest. Non-obstetricians including Emergency Physicians (EPs)
      are often called upon to perform this procedure under challenging and suboptimal
      circumstances. We reported a case of PMCS performed timely after traumatic
      cardiorespiratory arrest that resulted in fetal survival. A 25-year-old
      primigravida female and six-month pregnant presented to the Emergency Department
      (ED) of an adult tertiary hospital. She experienced traumatic cardiorespiratory
      arrest for nearly 27 min following a high-speed motor vehicle crash. Upon ED
      arrival, she was in pulseless electrical activity. She was immediately intubated
      with continuation of cardiopulmonary resuscitation. She received bilateral tube
      thoracostomies as well as intravenous (IV) transfusion of blood products,
      adrenaline and tranexamic acid. Her fundal height was two centimeters above the
      umbilicus on palpation. The EP performed a PMCS via a midline laparotomy 3-4 min
      upon ED arrival. The baby was bradycardic and cyanosed with no spontaneous
      respiration at birth and was resuscitated by a second EP. She was intubated and
      the EP gained IV access using a cannula introduced into the umbilical vein.
      Neonatal hypothermia was avoided using cling wrap. The baby was transported to a
      nearby neonatal intensive unit. She survived and is currently one year old. The
      mother, however, did not respond to our resuscitation and succumbed to her
      multiple injuries. We reviewed the limited literature regarding this potentially
      life-saving emergency procedure and highlighted the challenges facing our
      resuscitation team.

PMID- 30274761
TI  - Double sequential defibrillation and the tyranny of the case study.

PMID- 30274762
TI  - Pediatric hypertonic saline use in emergency departments.

PMID- 30274763
TI  - Protamine sulfate for the reversal of enoxaparin associated hemorrhage beyond 12
      h.
AB  - Clinical practice guidelines recommend protamine sulfate for reversal of
      enoxaparin associated bleeds dependent on the time from last administration and
      dose of enoxaparin. We present a case of a hemodynamically unstable patient with
      an enoxaparin induced abdominal wall hematoma/hemorrhage and the previous
      enoxaparin administration 21.5 h prior to presentation with a therapeutic anti-Xa
      assay (0.8 IU/mL) upon assessment in the emergency department. Along with
      resuscitative efforts, an interdisciplinary team collaborated to administer
      protamine sulfate 50 mg intravenous once (0.5 mg per 1 mg of enoxaparin) to
      reverse the therapeutic anticoagulation. Our case demonstrates the importance of
      monitoring renal function and the potential for accumulation of enoxaparin in
      patients with renal dysfunction leading to prolonged therapeutic anti-Xa assays.
      With the availability of anti-Xa assays, future reversal recommendations of
      enoxaparin associated bleeds using protamine sulfate should include the initial
      anti-Xa assay as a guide for the dosing regimen.

PMID- 30274764
TI  - Retrospective chart reviews: Assessing delays in IRB approval.

PMID- 30274765
TI  - Multimodal imaging and treatment of Purtscher-like retinopathy.
AB  - A 52-year-old patient with multiple cardiovascular risk factors referred for
      unilateral, acute, and painless visual loss. In the fundoscopic image there was
      significant papillary inflammation with tortuosity at this level and
      haemorrhages. Ophthalmological examination showed papillary inflammation, macular
      oedema, and involvement in retinal inner layers. The control fluorescein
      angiography and optical coherence tomography angiography showed areas of central
      and peripheral ischaemia. Given the clinical findings and background of the
      patient, the diagnosis of Purtscher-like retinopathy was reached and treatment
      with intravitreal dexamethasone was decided. Purtscher-like retinopathy is a rare
      entity that occurs in patients with multiple systemic pathologies, but without a
      traumatic background, which differentiates it from Purstcher's retinopathy. The
      diagnosis and early intervention are important in the prognosis. There are no
      therapeutic protocols, but good results have been obtained with intravitreal
      therapy with dexamethasone.

PMID- 30274766
TI  - Outcomes for Patients with Non-metastatic Triple-negative Breast Cancer in New
      Zealand.
AB  - AIMS: Triple-negative breast cancer (TNBC) has inferior outcomes to other
      subtypes of breast cancer. We studied the demographics and baseline breast cancer
      characteristics of patients in New Zealand with TNBC and assessed survival
      outcomes and prognostic/predictive factors. MATERIALS AND METHODS: We searched
      the New Zealand breast cancer registry database and identified patients with TNBC
      without distant metastatic disease. We retrieved demographic, tumour
      characteristic and treatment information. Locoregional recurrence-free survival,
      breast cancer-specific survival (BSS), metastasis-free survival (MRFS) and
      overall survival were determined. Predefined univariate and multivariate analyses
      were carried out investigating the association of survival outcomes with
      treatment and tumour characteristics. RESULTS: In total, 1390 patients were
      identified, with a median follow-up of 3.5 years. The median age was 55 years.
      Thirty-eight per cent were node positive and 79% were grade III. Mastectomy was
      carried out in 53%, adjuvant radiation delivered in 66% and chemotherapy in 69%.
      The significant predictive factors for overall survival, BSS and MRFS were
      radiotherapy, chemotherapy and neoadjuvant chemotherapy. The significant
      prognostic indicators were lymphovascular invasion, nodal status and tumour size.
      On Kaplan-Meier analysis, the 5 year overall survival was 72%. The median time to
      death for those who died was 3.55 years with 92% of deaths within 5 years.
      Seventy-four per cent of patients had distant metastasis as a first recurrence
      and isolated local recurrences occurred in only 4.5%. Metastatic disease occurred
      in lung (55.9%) and was in multiple sites in 51%. CONCLUSION: We report a large
      population-based series of TBNC without distant metastatic disease at diagnosis
      highlighting the unique behavioural characteristics of TNBC. Traditional
      therapies are positively associated with survival outcomes, and yet, particularly
      in the setting of recurrent disease, prognosis remains poor. Increased research
      into more effective systemic agents and the most effective timing of delivery of
      these may result in improved outcomes.

PMID- 30274767
TI  - Evaluation of Response to Stereotactic Radiosurgery in Brain Metastases Using
      Multiparametric Magnetic Resonance Imaging and a Review of the Literature.
AB  - AIMS: Following stereotactic radiosurgery (SRS), brain metastases initially
      increase in size in up to a third of cases, suggesting treatment failure. Current
      imaging using structural magnetic resonance imaging (MRI) cannot differentiate
      between tumour recurrence and SRS-induced changes, creating difficulties with
      patient management. Combining multiparametric MRI techniques, which assess tissue
      physiological and metabolic information, has shown promise in answering this
      clinical question. MATERIALS AND METHODS: Multiparametric MRI techniques,
      including spectroscopy, diffusion and perfusion imaging, were used for the
      differentiation of radiation-related changes and tumour recurrence after SRS for
      intracranial metastases in six cases. All patients presented with enlargement of
      the treated lesion, an increase in perilesional brain oedema and aggravation or
      appearance of neurological signs and symptoms from 7 to 29 weeks after primary
      treatment. RESULTS: Multiparametric imaging helped to differentiate features of
      tumour progression (n = 4) from radiation-related changes (n = 2). A low apparent
      diffusion coefficient (ADC) <1000 * 10-6 mm2/s, high relative cerebral blood
      volume (rCBV) ratio > 2.1, high choline:creatine (Cho:Cr) ratio > 1.8 suggested
      tumour recurrence. A high ADC > 1000 * 10-6 mm2/s, low rCBV ratio < 2.1, Cho:Cr
      ratio < 1.8 suggested SRS-induced radiation changes. Multiparametric MRI
      diagnosis was confirmed by histology or radiological and clinical follow-up.
      CONCLUSION: Multiparametric MRI was helpful in the early identification of
      radiation-related changes and tumour recurrence and may be useful for monitoring
      treatment changes in intracranial neoplasms after SRS treatment.

PMID- 30274768
TI  - Extended Cardiac Monitoring in Patients With Severe Sleep Apnea and No History of
      Atrial Fibrillation (The Reveal XT-SA Study).
AB  - Atrial fibrillation (AF) is a risk factor for ischemic stroke and reported to be
      associated with severe obstructive sleep apnea (OSA). The aim of this study was
      to determine the occurrence of newly detected AF in patients with severe OSA and
      no previous history of AF. Prospective observational study included patients with
      severe OSA (Apnea-Hypopnea Index [AHI] >= 30) and no history of AF. Primary
      outcome was detection of AF lasting >=10 seconds. Patients were subjected to 2 24
      hour Holter monitors, and if no AF was detected, implanted with a Medtronic
      Reveal XT implantable loop recorder. Follow-up was done every 6 months for a
      total of 3years. Implantable loop recorder was explanted if the primary outcome
      was detected (AF) or the battery was exhausted. Of the 31 patients enrolled, 6
      withdrew participation in the study before implantation. Mean age was 57 +/-
      10years, mean body mass index was 35 +/- 6; 52% male patients. Hypertension 56%
      and coronary artery disease 24%. Mean AHI was 55 +/- 18. AF was detected in 5
      patients (20%). AF mean duration was 4.8hours (range 20 seconds to 15.3 hours).
      Mean time to diagnosis was 11 +/- 7 months. Male gender was predictive for AF
      detection (p = 0.04). Continuous positive airway pressure therapy was used by 96%
      of patients with 68% total adherence. Mean follow-up was 27 months. In
      conclusion, extended cardiac monitoring of patients with severe OSA may
      facilitate the identification of newly detected AF.

PMID- 30274769
TI  - Regulated acetylation and deacetylation of H4 K16 is essential for efficient NER
      in Saccharomyces cerevisiae.
AB  - Acetylation status of H4 K16, a residue in the histone H4 N-terminal tail plays a
      unique role in regulating chromatin structure and function. Here we show that,
      during UV-induced nucleotide excision repair H4 K16 gets hyperacetylated
      following an initial phase of hypoacetylation. Disrupting H4 K16 acetylation
      deacetylation by mutating H4 K16 to R (deacetylated state) or Q (acetylated
      state) leads to compromised chromatin functions. In the silenced mating locus and
      telomere region H4 K16 mutants show higher recruitment of Sir proteins and
      spreading beyond the designated boundaries. More significantly, chromatin of both
      the H4 K16 mutants has reduced accessibility in the silenced regions and genome
      wide. On UV irradiation, the mutants showed higher UV sensitivity, reduced NER
      rate and altered H3 N-terminal tail acetylation, compared to wild type. NER
      efficiency is affected by reduced or delayed recruitment of early NER proteins
      and chromatin remodeller Swi/Snf along with lack of nucleosome rearrangement
      during repair. Additionally UV-induced expression of RAD and SNF5 genes was
      reduced in the mutants. Hindered chromatin accessibility in the H4 K16 mutants is
      thus non-conducive for gene expression as well as recruitment of NER and
      chromatin remodeller proteins. Subsequently, inadequate nucleosomal rearrangement
      during early phases of repair impeded accessibility of the NER complex to DNA
      lesions, in the H4 K16 mutants. Effectively, NER efficiency was found to be
      compromised in the mutants. Interestingly, in the transcriptionally active
      chromatin region, both the H4 K16 mutants showed reduced NER rate during early
      repair time points. However, with progression of repair H4 K16R repaired faster
      than K16Q mutants and rate of CPD removal became differential between the two
      mutants during later NER phases. To summarize, our results establish the
      essentiality of regulated acetylation and deacetylation of H4 K16 residue in
      maintaining chromatin accessibility and efficiency of functions like NER and gene
      expression.

PMID- 30274770
TI  - 18F-Choline-PET in parathyroid carcinoma.

PMID- 30274771
TI  - Blood pressure control and impact on cardiovascular events in patients with type
      2 diabetes mellitus: A critical analysis of the literature.
AB  - High blood pressure in individuals with type2 diabetes mellitus increases the
      risk of cardiovascular events. The international management guidelines recommend
      starting pharmacological treatment with blood pressure values >140/90mmHg.
      However, there is no optimal cut-off point from which cardiovascular events can
      be reduced without causing adverse events. A blood pressure range of >130/80 to
      <140/90mmHg seems to be adequate. These values can be achieved through non
      pharmacological (diet, exercise) and pharmacological interventions (using drugs
      that have been shown to reduce cardiovascular events). The choice of one or
      several drugs must be individualised, according to factors including, ethnicity,
      age, and associated comorbidities, among others.

PMID- 30274774
TI  - The galectin LEC-5 is a novel binding partner for RAB-11.
AB  - RAB-11/Rab11 is an endosomal GTPase with conserved roles in directional
      trafficking and apical domain formation in polarized epithelial cells. From a
      yeast two-hybrid screen using full-length C. elegans RAB-11 as bait, we
      identified LEC-5 as a novel binding protein for RAB-11. LEC-5 is an ortholog of
      mammalian Galectin-9 which associates with glycosphingolipids and is implicated
      in apical cargo sorting. We further confirmed the interaction between RAB-11 and
      LEC-5 via GST-pull down, co-immunoprecipitation and bimolecular fluorescence
      complementation. In addition, we showed that LEC-5 binds to RAB-11 with its C
      terminus. Our results indicate a novel role of RAB-11 in apical sorting via LEC
      5. Such a role would extend RAB-11's function as a master regulator of apical
      trafficking and suggest it could translate apical sorting signals into apical
      vesicle directionality.

PMID- 30274773
TI  - beta1,6 GlcNAc branches-modified protein tyrosine phosphatase Mu attenuates its
      tyrosine phosphatase activity and promotes glioma cell migration through PLCgamma
      PKC pathways.
AB  - The metastatic potential of malignant tumor has been shown to be correlated with
      the increased expression of tri- and tetra-antennary beta1,6-N-acetylglucosamine
      (beta1,6-GlcNAc) N-glycans. In this study, We found that GnT-V expression was
      negatively correlated with receptor protein tyrosine phosphatase type MU(RPTPMU)
      in human glioma tissues. To study whether RPTPMU is a novel substance of GnT-V
      which further affect RPTPMU's downstream dephosphorylation function, we preform
      lentiviral infection with GnT-V gene to construct stably transfected GnT-V glial
      cell lines. We found RPTPMU undergone severer cleavage in GnT-V transfected
      glioma cells compare to Mock cells. RPTPMU intracellular domain fragments
      increased while beta1,6-GlcNAc-branched N-glycans increased, in consistent with
      the decrease of RPTPMU's catalytic activity. The results showed that abnormal
      glycosylation could decrease the phosphorylation activity of PTP MU, and affect
      PLCgamma-PKC pathways. Both protease inhibitor Furin and N-glycan biosynthesis
      inhibitor swainsonine could decrease cell mobility in GnT-V-U87 transfectants and
      other glioma cell lines. All results above suggest increased post-translational
      modification of RPTPMU N-glycans by GnT-V attenuates its tyrosine phosphatase
      activity and promotes glioma cell migration through PLCgamma-PKC pathways, and
      that the beta1,6-GlcNAc-branched N-glycans of RPTPMU play a crucial role in
      glioma invasivity.

PMID- 30274775
TI  - Long non-coding RNA OGFRP1 regulates LYPD3 expression by sponging miR-124-3p and
      promotes non-small cell lung cancer progression.
AB  - Long noncoding RNA (OGFRP1) has been reported to be involved in the progression
      of non-small cell lung cancer (NSCLC). However, the expression pattern, functions
      and molecular mechanisms of OGFRP1 in NSCLC remains unclear. In the present
      study, we found that OGFRP1 expression was significantly up-regulated in both
      NSCLC tissues and cell lines, and the upregulation of OGFRP1 expression is a
      powerful predictor of advanced clinical stage, lymph nodes metastasis and poor
      prognosis for NSCLC patients. Loss-of-function assay indicated that knockdown of
      OGFRP1 inhibited proliferation, migration and invasion, and induced apoptosis in
      vitro. Mechanistically, OGFRP1 could directly bind to miR-124-3p and effectively
      act as a competing endogenous RNA (ceRNA) for miR-124-3p to promote the
      expression of the target gene LYPD3. Taken together, OGFRP1 contributed to
      progression of NSCLC at least partly through upregulating LYPD3 expression by
      sponging miR-124-3p, indicating that OGFRP1 may be a novel prognostic biomarker
      and therapeutic target in NSCLC.

PMID- 30274776
TI  - Protective effect of electro-acupuncture at maternal different points on
      perinatal nicotine exposure-induced pulmonary dysplasia in offspring based on HPA
      axis and signal transduction pathway.
AB  - Perinatal nicotine exposure can not only lead to lung dysplasia in offspring, but
      also cause epigenetic changes and induce transgenerational asthma. Previous
      studies have shown that electro-acupuncture (EA) applied to "Zusanli" (ST 36) can
      improve the lung morphology and correct abnormal expression of lung development
      related protein in perinatal nicotine exposure offspring. However, it is still
      unclear whether ST 36 has a specific therapeutic effect and how maternal
      acupuncture can protect the offspring from pulmonary dysplasia. In this study, we
      compared the different effect of ST 36 and "Fenglong" (ST 40), which belong to
      the same meridian, in terms of lung pulmonary function and morphology, PPARgamma,
      beta-catenin, GR levels in the lung tissues and CORT in the serum of perinatal
      nicotine exposure offspring, and explored the mechanism of acupuncture based on
      the maternal hypothalamus-pituitary-adrenal (HPA) axis. It is shown that EA
      applied to ST 36 could restore the normal function of maternal HPA axis and
      alleviate maternal glucocorticoid overexposure in offspring, thereby it can up
      regulate the PTHrP/PPARgamma and down-regulate the Wnt/beta-catenin signaling
      pathways, and protects perinatal nicotine exposure-induced pulmonary dysplasia in
      offspring. Its effect is better than that of ST 40. These results are of great
      significance in preventing perinatal nicotine exposure-induced pulmonary
      dysplasia in offspring.

PMID- 30274777
TI  - MiR-374b-5p-FOXP1 feedback loop regulates cell migration, epithelial-mesenchymal
      transition and chemosensitivity in ovarian cancer.
AB  - MicroRNAs (miRNAs) are important regulators in tumorigenesis and progression of
      multiple human cancers, including ovarian cancer (OC). As a member of miRNAs
      family, miR-374b-5p has been reported to be a tumor suppressive gene in human
      cancers. In this study, the lower expression of miR-374b-5p was identified in OC
      tissues and cell liens using quantitative real time PCR (qRT-PCR). Forkhead box
      protein P1 (FOXP1) can act as an oncogene in human cancers. Mechanism experiments
      revealed that FOXP1 is a target of miR-374b-5p. Functionally, miR-374b-5p
      suppressed cell proliferation, migration and epithelial-mesenchymal transition
      (EMT) in ovarian cancer. Moreover, the sensitivity of OC cells to cisplatin was
      markedly enhanced by miR-374b-5p. However, FOXP1 reversed However, FOXP1 reversed
      miR-374b-5p-mediated biological functions. Previous reports demonstrated the
      inhibitory effect of FOXP1 on transcription FOXP1. Thus, we further examined the
      effect of FOXP1 on the transcription activity of miR-374b-5p in OC cells. The
      results showed that FOXP1 decreased miR-374b-5p expression by inhibiting the
      transcription activity of miR-374b-5p. Rescue assays revealed the regulatory
      effect of miR-374b-5p-FOXP1 feedback loop on ovarian cancer progression. In
      conclusion, miR-374b-5p-FOXP1 feedback loop regulates tumor progression and
      chemosensitivity in ovarian cancer.

PMID- 30274778
TI  - Low dose Emodin induces tumor senescence for boosting breast cancer chemotherapy
      via silencing NRARP.
AB  - PURPOSE: The resistance to 5-FU often limits its clinical effectiveness on breast
      cancer treatment. Combination therapy thus is employed to overcome this treatment
      resistance. We here report a potent antitumor effect of Emodin at low dose on
      chemotherapy sensitivity of MCF-7 breast cancer cells. METHODS: Cell viability,
      apoptosis, glutathiones (GSH) concentration and Reactive oxygen species (ROS)
      activity following Emodin and 5-FU treatment was assessed. Cellular senescence
      following combined treatment and silence of NRARP was examined by senescence
      associated beta-galactosidase analysis. Western blot analysis was used to
      determine changes in the expression of p21, p16, p27, E2F1 and NRARP. RESULTS:
      Low dose Emodin potentiates 5-FU-induced apoptosis of breast cancer cells, in
      association with inhibition of NRARP, resulting in cellular senescence. RNA
      interference of NRARP induced cellular senescence in MCF-7 breast cancer cells.
      Furthermore, the cellular senescence induced by Emodin and 5-FU treatment could
      be reverted by pcDNA-NRARP. CONCLUSION: These findings provide preclinical
      evidence for repurposing use of Emodin in combination with chemotherapeutic
      agents to treat breast cancer as an alternative salvage regimen.

PMID- 30274779
TI  - Induced protein degradation of anaplastic lymphoma kinase (ALK) by proteolysis
      targeting chimera (PROTAC).
AB  - Recently, proteolysis targeting chimera (PROTAC) technology is highlighted in
      drug discovery area as a new therapeutic approach. PROTAC as a heterobifunctional
      molecule is comprised of two ligands, which recruit target protein and E3 ligase,
      respectively. To degrade the anaplastic lymphoma kinase (ALK) fusion protein,
      such as NPM-ALK or EML4-ALK, we generated several ALK-PROTAC molecules consisted
      of ceritinib, one of the ALK inhibitors, and ligand of von Hippel-Lindau (VHL) E3
      ligase. Among these molecules, TD-004 effectively induced ALK degradation and
      inhibited the growth of ALK fusion positive cell lines, SU-DHL-1 and H3122. We
      also confirmed that TD-004 significantly reduced the tumor growth in H3122
      xenograft model.

PMID- 30274780
TI  - SDF-1/CXCR4 axis promotes the growth and sphere formation of hypoxic breast
      cancer SP cells by c-Jun/ABCG2 pathway.
AB  - ATP-binding cassette sub-family G member 2 (ABCG2) confers to the major
      phenotypes of side population (SP) cells, the cancer stem-like cells. In this
      study, the SP cells displayed a distinctly higher ABCG2 expression level, sphere
      formation efficiency (SFE) and growth rate even under hypoxia condition. CXCR4
      overexpression by pcDNA-CXCR4 transfection robustly increased ABCG2 expression,
      and promoted SFE and growth of hypoxic SP cells, while CXCR4 inhibitor AMD3100
      could suppress the promotion. Additionally, we found that CXCR4 promoted the
      expression of c-Jun, a major gene in the oncogenic JNK/c-Jun pathway. Our data on
      electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation
      (ChIP) assays both showed that c-Jun directly bound with the ABCG2 promoter
      sequence. Moreover, overexpression of JNK/c-Jun promoted ABCG2 expression, SFE,
      and growth of hypoxic SP cells and the promotion could be rescued by c-Jun
      inhibitor SP600125. In conclusion, CXCR4 increases the growth and SFE of breast
      cancer SP cells under hypoxia through c-Jun-mediated transcriptional activation
      of ABCG2.

PMID- 30274781
TI  - DNA polymerase beta deficiency in the p53 null cerebellum leads to
      medulloblastoma formation.
AB  - Defects in DNA damage response or repair mechanisms during neurogenesis result in
      genomic instability, which is causative for several neural defects. These include
      brain tumors, particularly medulloblastoma, which occurs in the cerebellum with a
      high incidence in children. We generated an animal model with defective base
      excision repair during brain development through selective inactivation of DNA
      polymerase beta (Polb) in neuroprogenitor cells. All of Polb conditional knockout
      mice developed medulloblastoma in a p53 null background, similar to the Xrcc1 and
      p53 double deficient animal model. XRCC1 is a scaffolding protein which is
      involved in DNA damage repair and binds to POLB. In both animal models, the
      histopathological characteristics of the medulloblastoma were similar to those of
      human classic medulloblastoma. Brain tumor development was slower in the Polb and
      p53 double null animals than in the Xrcc1 and p53 double knockout animals.
      Molecular marker analysis suggested that Polb- and Xrcc1-deficient
      medulloblastomas belonged to the SHHalpha subtype, underscoring the important
      role of genomic stability in preventing this devastating pediatric cerebellar
      tumor.

PMID- 30274782
TI  - Evaluation of collagen mixture on promoting skin wound healing in zebrafish
      caused by acetic acid administration.
AB  - The aim of this study is to use zebrafish embryos as a quick platform for wound
      healing studies. At beginning, we optimized a protocol to induce skin lesion by
      acetic acid injection. The acetic acid injection induced regional inflammation
      wound hyperpigmentation by recruiting pigment cells to the wound area. Later, we
      applied established platform to evaluate the effect of tilapia's collagen peptide
      mixtures, including demonstration on promoting skin wound healing and eliminating
      inflammatory response. Results showed that after treating TY001, one of the above
      fish collagen peptide mixtures, not only repair and proliferation were induced,
      but also death and apoptosis cells were cleared within cutaneous lesion.
      Moreover, inflammatory response was suppressed along with collagen mixture
      treatment. Finally, the TY001-associated signaling was validated by real time
      PCR, and numbers of gene associated with tissue repair and vessel proliferation
      were induced. To sum up, our findings provided a permissive model that may apply
      to generate a platform for further screening on repair and restoration
      technology. In addition, the tilapia fish collagen peptide mixture we applied on
      our model has great potential on developing clinical application on wound
      healing.

PMID- 30274783
TI  - Internal Limiting Membrane Peeling in Macula-off Retinal Detachment Complicated
      by Grade B Proliferative Vitreoretinopathy.

PMID- 30274784
TI  - Reply.

PMID- 30274785
TI  - lncRNA GCAWKR Promotes Gastric Cancer Development by Scaffolding the Chromatin
      Modification Factors WDR5 and KAT2A.
AB  - Long noncoding RNAs (lncRNAs) have been demonstrated to play a role in
      carcinogenesis, but their mechanisms of function remain elusive. We explored the
      mechanisms of the oncogenic role of GCAWKR in gastric cancer (GC) using human
      tissues and cell lines. The in situ hybridization analysis was utilized to
      determine GCAWKR levels in samples from 42 GC patients and real-time qPCR in
      tissues from 123 patients. The GCAWKR levels were modulated in GC cell lines, and
      relevant biological and molecular analyses were performed. Levels of the GCAWKR
      were upregulated in GC tissues compared with normal tissues and associated with
      tumor size, lymph node metastasis, TNM stage, and patient outcomes. GCAWKR
      affected cell proliferation and cell invasion in multiple GC models.
      Mechanistically, GCAWKR bound WDR5 and KAT2A and acted as a molecular scaffold of
      WDR5/KAT2A complexes, modulating the affinity for WDR5/KAT2A complexes in the
      target gene's promoter region. Thus, our data defined a mechanism of lncRNA
      mediated carcinogenesis in GC, suggesting new therapeutic targets in GC.

PMID- 30274787
TI  - MicroRNA-532-5p Regulates Pericyte Function by Targeting the Transcription
      Regulator BACH1 and Angiopoietin-1.
AB  - MicroRNAs regulate endothelial function and angiogenesis, but their implication
      in pericyte biology remains undetermined. A PCR array, covering a panel of 379
      human microRNAs, showed microRNA-532-5p to be one of the most differentially
      modulated by hypoxia, which was confirmed by qPCR in both skeletal muscle and
      adventitial pericytes. Furthermore, microRNA-532-5p was upregulated in murine
      muscular pericytes early after experimentally induced ischemia, decreasing below
      baseline after reperfusion. Transfection of human pericytes with anti-microRNA,
      microRNA-mimic, or controls indicates microRNA-532-5p modulates pro-angiogenic
      activity via transcriptional regulation of angiopoietin-1. Tie-2 blockade
      abrogated the ability of microRNA-532-5p-overexpressing pericytes to promote
      endothelial network formation in vitro. However, angiopoietin-1 is not a direct
      target of microRNA-532-5p. In silico analysis of microRNA-532-5p inhibitory
      targets associated with angiopoietin-1 transcription indicated three potential
      candidates, BACH1, HIF1AN, and EGLN1. Binding of microRNA-532-5p to the BACH1 3'
      UTR was confirmed by luciferase assay. MicroRNA-532-5p silencing increased BACH1,
      while a microRNA-532-5p mimic decreased expression. Silencing of BACH1 modulated
      angiopoietin-1 gene and protein expression. ChIP confirmed BACH1 transcriptional
      regulation of angiopoietin-1 promoter. Finally, microRNA-532-5p overexpression
      increased pericyte coverage in an in vivo Matrigel assay, suggesting its role in
      vascular maturation. This study provides a new mechanistic understanding of the
      transcriptional program orchestrating angiopoietin-1/Tie-2 signaling in human
      pericytes.

PMID- 30274786
TI  - RNAi-Mediated beta-Catenin Inhibition Promotes T Cell Infiltration and Antitumor
      Activity in Combination with Immune Checkpoint Blockade.
AB  - Wnt/beta-catenin signaling mediates cancer immune evasion and resistance to
      immune checkpoint therapy, in part by blocking cytokines that trigger immune cell
      recruitment. Inhibition of beta-catenin may be an effective strategy for
      increasing the low response rate to these effective medicines in numerous cancer
      populations. DCR-BCAT is a nanoparticle drug product containing a chemically
      optimized RNAi trigger targeting CTNNB1, the gene that encodes beta-catenin. In
      syngeneic mouse tumor models, beta-catenin inhibition with DCR-BCAT significantly
      increased T cell infiltration and potentiated the sensitivity of the tumors to
      checkpoint inhibition. The combination of DCR-BCAT and immunotherapy yielded
      significantly greater tumor growth inhibition (TGI) compared to monotherapy in
      B16F10 melanoma, 4T1 mammary carcinoma, Neuro2A neuroblastoma, and Renca renal
      adenocarcinoma. Response to the RNAi-containing combination therapy was not
      dependent on Wnt activation status of the tumor. Importantly, this drug
      combination was associated with elevated levels of biomarkers of T cell-mediated
      cytotoxicity. Finally, when CTLA-4 and PD-1 antibodies were combined with DCR
      BCAT in MMTV-Wnt1 transgenic mice, a genetic model of spontaneous Wnt-driven
      tumors, complete regressions were achieved in the majority of treated subjects.
      These data support RNAi-mediated beta-catenin inhibition as an effective strategy
      to increase response rates to cancer immunotherapy.

PMID- 30274790
TI  - Recombinant BCG Overexpressing phoP-phoR Confers Enhanced Protection against
      Tuberculosis.
AB  - The live tuberculosis vaccine Mycobacterium bovis BCG (Bacille Calmette-Guerin)
      comprises a number of genetically distinct substrains. In BCG-Prague, phoP of the
      PhoP-PhoR two-component system is a pseudogene due to a single insertion
      mutation. We hypothesized that this mutation partially accounts for the low
      immunogenicity of BCG-Prague observed in the 1970s. In this study, we showed that
      complementation with the M. bovis allele of phoP restored BCG-Prague's
      immunogenicity. Furthermore, we showed that overexpression of the M. bovis allele
      of phoP-phoR in BCG-Japan, a strain already containing a copy of phoP-phoR,
      further enhanced immunogenicity and protective efficacy. Vaccination of C57BL/6
      mice with the recombinant strain rBCG-Japan/PhoPR induced higher levels of
      interferon-gamma (IFN-gamma) production by CD4+ T cells than that with the
      parental BCG. Guinea pigs vaccinated with rBCG-Japan/PhoPR were better protected
      against challenge with Mycobacterium tuberculosis than those immunized with the
      parental BCG, showing significantly longer survival time, reduced bacterial
      burdens, and less severe pathology. Taken together, our study has identified a
      genetic modification that could be generally applied to generate new recombinant
      BCG vaccines.

PMID- 30274789
TI  - Engineering the Direct Repeat Sequence of crRNA for Optimization of FnCpf1
      Mediated Genome Editing in Human Cells.
AB  - FnCpf1-mediated genome-editing technologies have enabled a broad range of
      research and medical applications. Recently, we reported that FnCpf1 possesses
      activity in human cells and recognizes a more compatible PAM (protospacer
      adjacent motif, 5'-KYTV-3'), compared with the other two commonly used Cpf1
      enzymes (AsCpf1 and LbCpf1), which requires a 5'-TTTN-3' PAM. However, due to the
      efficiency and fidelity, FnCpf1-based clinical and basic applications remain a
      challenge. The direct repeat (DR) sequence is one of the key elements for FnCpf1
      mediated genome editing. In principle, its engineering should influence the
      corresponding genome-editing activity and fidelity. Here we showed that the DR
      mutants [G(-9)A and U(-7)A] could modulate FnCpf1 performance in human cells,
      enabling enhancement of both genome-editing efficiency and fidelity. These newly
      identified features will facilitate the design and optimization of CRISPR-Cpf1
      based genome-editing strategies.

PMID- 30274788
TI  - Therapeutic Genome Editing for Myotonic Dystrophy Type 1 Using CRISPR/Cas9.
AB  - Myotonic dystrophy type 1 (DM1) is caused by a CTG nucleotide repeat expansion
      within the 3' UTR of the Dystrophia Myotonica protein kinase gene. In this study,
      we explored therapeutic genome editing using CRISPR/Cas9 via targeted deletion of
      expanded CTG repeats and targeted insertion of polyadenylation signals in the 3'
      UTR upstream of the CTG repeats to eliminate toxic RNA CUG repeats. We found
      paired SpCas9 or SaCas9 guide RNA induced deletion of expanded CTG repeats.
      However, this approach incurred frequent inversion in both the mutant and normal
      alleles. In contrast, the insertion of polyadenylation signals in the 3' UTR
      upstream of the CTG repeats eliminated toxic RNA CUG repeats, which led to
      phenotype reversal in differentiated neural stem cells, forebrain neurons,
      cardiomyocytes, and skeletal muscle myofibers. We concluded that targeted
      insertion of polyadenylation signals in the 3' UTR is a viable approach to
      develop therapeutic genome editing for DM1.

PMID- 30274791
TI  - Quantification of circulating miR-125b-5p predicts survival in chronic hepatitis
      B patients with acute-on-chronic liver failure.
AB  - AIMS: To analyze the role of serum miR-125b-5p in reflecting liver damage and
      predicting outcomes in chronic hepatitis B (CHB) patients with acute-on-chronic
      liver failure (ACLF). METHODS: CHB patients with normal hepatic function (n =
      100), moderate-to-severe liver damage (n = 90), and ACLF (n = 136) were included.
      Among hepatitis B virus (HBV)-ACLF patients, 86 and 50 were in the training and
      validation cohorts, respectively. Serum miR-125b-5p level was measured by
      quantitative real-time PCR. RESULTS: Serum miR-125b-5p level increased with
      disease progression, and serum miR-125b-5p level was lower in surviving than in
      dead HBV-ACLF patients. Among HBV-ACLF patients, miR-125b-5p positively
      correlated with total bilirubin (TBil; r = 0.214, p < 0.05) and model for end
      stage liver disease (MELD) score (r = 0.382, p < 0.001) and negatively correlated
      with prothrombin activity(PTA; r = -0.215, p < 0.05). MiR-122 showed a
      contrasting performance compared with miR-125b-5p. Cox regression analysis showed
      that miR-125b-5p, miR-122, and PTA were independent survival predictors for HBV
      ACLF, and low miR-125b-5p and high miR-122 levels may predict a longer survival
      in HBV-ACLF. MiR-125b-5p (AUC = 0.814) had a higher performance for survival
      prediction in HBV-ACLF compared with miR-122 (AUC = 0.804), PTA (AUC = 0.762),
      MELD score (AUC = 0.799), and TBil (AUC = 0.670) alone; predictive effectiveness
      of miR-125b-5p was increased by combination with miR-122 (AUC = 0.898). MiR-125b
      5p was an effective predictor of HBV-ACLF outcomes in the validation cohort.
      CONCLUSIONS: MiR-125b-5p increase is associated with severity of liver damage;
      high serum miR-125b-5p may serve as a predictor for poor outcomes in HBV-ACLF
      cases.

PMID- 30274792
TI  - Should we set-up routine screening for primary sclerosing cholangitis in all IBD
      patients?

PMID- 30274793
TI  - SAPHO syndrome in pediatric patients with inflammatory bowel disease treated with
      infliximab.

PMID- 30274794
TI  - The relationship between oily fish intake and arterial stiffness in older adults
      living in rural coastal Ecuador.

PMID- 30274795
TI  - Assessment of lesion-specific ischemia using fractional flow reserve (FFR)
      profiles derived from coronary computed tomography angiography (FFRCT) and
      invasive pressure measurements (FFRINV): Importance of the site of measurement
      and implications for patient referral for invasive coronary angiography and
      percutaneous coronary intervention.
AB  - BACKGROUND: Fractional flow reserve (FFR)-derived from computed tomography
      angiography (CTA; FFRCT) and invasive FFR (FFRINV) are used to assess the need
      for invasive coronary angiography (ICA) and percutaneous coronary intervention
      (PCI). The optimal location for measuring FFR and the impact of measurement
      location have not been well defined. METHODS: 930 patients (age 60.7 + 10 years,
      59% male) were included in this study. Normal and diseased coronary arteries were
      classified into stenosis grades 0-4 in the left anterior descending artery (LAD,
      n = 518), left circumflex (LCX, n = 112) and right coronary artery (RCA, n =
      585). FFRCT (n = 1215 arteries) and FFRINV (n = 26 LAD) profiles were developed
      by plotting FFR values (y-axis) versus site of measurement (x-axis: ostium,
      proximal, mid, distal segments). The best location to measure FFR was defined
      relative to the distal end of the stenosis. FFR <=0.8 was considered positive for
      ischemia. RESULTS: In normal and stenotic coronary arteries there are significant
      declines in FFRCT and FFRINV from the ostium to the distal vessel (p < 0.001),
      due to lesion-specific ischemia and to effects unrelated to the lesion. A
      reliable location (distal to the stenosis) is 10.5 mm [IQR 7.3-14.8 mm] for FFRCT
      and within 20-30 mm for FFRINV. Rates of positive FFR (from the distal vessel)
      reclassified to negative FFR (distal to the stenosis) are 61% (FFRCT) and 33%
      (FFRINV). CONCLUSION: FFRCT and FFRINV values are influenced by stenosis severity
      and the site of measurement. FFR measurements from the distal vessel may over
      estimate lesion-specific ischemia and result in unnecessary referrals for ICA and
      PCI.

PMID- 30274796
TI  - Alterations in enteric calcitonin gene-related peptide in patients with colonic
      diverticular disease: CGRP in diverticular disease.
AB  - Diverticular disease (DD) is one of the most prevalent diseases of the large
      bowel. Lately, imbalance of neuro-muscular transmission has been recognized as a
      major etiological factor for DD. Neuronal calcitonin gene-related peptide (CGRP)
      is a potent gastrointestinal smooth muscle relaxant shown to have a widespread
      effect within the alimentary tract. Nevertheless, CGRPergic innervation of the
      enteric ganglia has never been considered in the context of motility impairment
      observed in DD patients. Changes in CGRP and calcitonin receptor-like receptor
      (CRLR) abundance within enteric ganglia were investigated in sigmoid samples from
      symptomatic and asymptomatic DD patients using quantitative fluorescence
      microscopy. CGRP effect on gastrointestinal smooth muscle was investigated using
      organ bath technique. We found CGRP levels within the enteric ganglia to be
      declined by up to 52% in symptomatic DD patients. Conversely, CRLR within the
      enteric ganglia was upregulated by 41% in symptomatic DD. Longitudinal smooth
      muscle displayed an elevated (+10.5%) relaxant effect to the exogenous
      application of CGRP in colonic strips from symptomatic DD patients. Samples from
      asymptomatic DD patients consistently showed intermediate values across different
      experiments. In conclusion, the present study demonstrates that CGRPergic
      signaling is subject to alteration in DD. Our results suggest that a
      hypersensitization mechanism to gradually decreasing levels of CGRP-IR nerve
      fibers takes place during DD progression. Alterations to CGRPergic signaling in
      DD disease may have implications for physiological abnormalities associated with
      colonic DD.

PMID- 30274797
TI  - Screening of microorganisms producing a novel protein-asparaginase and
      characterization of the enzyme derived from Luteimicrobium album.
AB  - A screening system using enrichment culture has been established with the aim of
      obtaining a novel enzyme for protein modification that has not been previously
      reported. This enzyme catalyzes deamidation of the side-chain amide group of
      asparagine in proteins. Enrichment culture of 390 soil samples was carried out
      with Z-Asn-Gly as the sole source of nitrogen, and the reaction product, Z-Asp
      Gly, was detected in the culture supernatant of 102 strains. Strains with
      particularly high activity were Leifsonia sp., Luteimicrobium sp., Microbacterium
      sp., and Agromyces sp., all belonging to the class Actinobacteria. Of these, a
      protein-asparaginase (PA) was obtained from the culture supernatant of
      Luteimicrobium album 333B-h1, and its reactivity with different substrates and
      its basic enzymatic characteristics were investigated. Addition of the enzyme
      solution resulted in specific deamidation of only the asparagine residue in
      insulin chain B. The enzyme showed no reactivity with free asparagine or
      asparagine in low molecular weight peptides. It was demonstrated that the enzyme
      reacts with various protein substrates. In particular, proteins that have open
      structures, such as casein or gelatin, were good substrates. The activity and
      stability of PA at different temperatures and pH values were investigated. It was
      found that a temperature of 37 degrees C and a roughly neutral pH are optimal
      conditions for the enzyme.

PMID- 30274798
TI  - Targeted proteome analysis of microalgae under high-light conditions by optimized
      protein extraction of photosynthetic organisms.
AB  - Cell disruption and protein solubilization protocols for the relative
      quantification of individual subunits in photosystems were developed for
      photosynthetic organisms including cyanobacterium Synechocystis sp. PCC 6803,
      green-algae Chlamydomonas reinhardtii, and seed plant Arabidopsis thaliana. The
      optimal methods for the disruption of Chlamydomonas, Synechocystis, and
      Arabidopsis cells were sonication, microbeads (Phi approximately 0.1 mm), and
      large beads (Phi = 5.0 mm), respectively. Extraction of the total proteins
      exceeded 90% using each optimal cell disruption method. Solubilization efficiency
      of membrane proteins was improved by the phase transfer surfactant (PTS) method.
      Ninety seven and 114 proteins from Chlamydomonas and Synechocystis, respectively,
      including membrane proteins such as photosystem proteins, ATP synthase, and NADH
      dehydrogenase, were successfully analyzed by nano-liquid chromatography tandem
      mass spectrometry. These results also indicated the improved efficiency of
      solubilization and trypsin digestion using PTS buffer. The results of the
      relative quantitative evaluation of photosystem subunits in Chlamydomonas and
      Synechocystis grown under high-light conditions were consistent with those of
      previous studies. Thus, the optimal cell disruption and PTS methods allow for
      comprehensive relative quantitative proteome analysis of photosynthetic
      organisms. Additionally, NdhD1 and NdhF1, which are NDH-1 subunit homologs, were
      increased under high-light conditions, suggesting that the NDH-1L complex,
      including NdhD1 and NdhF1, is increased under high-light conditions. The relative
      quantitative proteome analysis of individual subunits indicates the diverse
      functions of NDH-1 protein.

PMID- 30274799
TI  - Cultural Humility for Consultation-Liaison Psychiatrists.
AB  - BACKGROUND: Case presentation and analysis is a useful way to revisit key
      clinical themes, broad concepts, and teach others, especially when it comes to
      cross-cultural clinical issues. Patients from different cultural backgrounds tend
      to have different explanatory models of illnesses and related help seeking
      behaviors. Ineffective communication between clinicians and patients from
      nonmajority cultural groups may lead to less satisfaction with care and
      disparities in access to health care and in treatment outcomes. CONCLUSIONS: To
      address health disparities, psychiatrists need to be able to understand the
      illness beliefs of all patients, particularly those from diverse cultural
      backgrounds. Using cultural humility to work with patients from all cultures by
      understanding the patients' values and preferences is a key attitude for
      successful cross-cultural clinical encounters.

PMID- 30274800
TI  - Patient Safety and Quality Improvement: Driving to New Frontiers.

PMID- 30274801
TI  - Evidence-based medicine in trauma/acute care surgery- what does that look like?

PMID- 30274802
TI  - Is oncoplastic breast surgery truly associated with a lower rate of surgical site
      complications compared to standard breast conserving surgery?

PMID- 30274803
TI  - "Are we there yet?"- factors affecting postoperative follow-up after general
      surgery procedures.
AB  - BACKGROUND: Surgical follow-up allows patients to discuss pathology and
      preventative maintenance. Multiple factors impact patients' compliance with
      surgical follow-up. We hypothesized that increased travel time would be
      associated with lack of post-discharge surgical follow-up. METHODS: Retrospective
      analysis identified patients undergoing laparoscopic appendectomy or laparoscopic
      cholecystectomy. Descriptive statistics and logistic regression assessed the
      relationship between patient characteristics and post-discharge follow-up.
      RESULTS: We identified 1830 patients from 2015-2016. 31% did not complete follow
      up, were more likely to have had an appendectomy, be un- or underinsured, not
      married, and live outside North Carolina. Median round-trip travel time was not
      significantly different. After adjustment for patient factors, each additional 10
      min of travel time increased the odds of not following up by 6% (p < 0.01).
      CONCLUSIONS: Travel time was the only modifiable factor associated with post
      discharge follow-up. Novel methods of completing follow-up that minimize travel
      time, such as virtual visits, may increase compliance with recommended follow-up.

PMID- 30274804
TI  - Does a fracture liaison service program minimize recurrent fragility fractures in
      the elderly with osteoporotic vertebral compression fractures?
AB  - BACKGROUND: There is a sizable proportion of elderly, both men and women, with
      fragility fractures, approximately 2 million fractures per year in the United
      States. METHODS: A retrospective chart review of 365 patient presented between
      January 2012 and December 2017 with vertebral compression fractures. Pre-post
      study design to determine refracture between Group A (before Fracture Liaison
      Service (FLS)) and Group B, after. Calcium, Vitamin D, DEXA scans, FRAX scores,
      and refracture rates were measured. RESULTS: Mean age for group A and B were 79.0
      and 74.9 years, respectively, and predominantly females. Serum calcium was higher
      in group B (9.51 mg/d/L versus 9.40 mg/dL) but not significant (p = 0.19).
      Fracture score among the groups was similar (20% versus 22%; p = 0.44). The total
      refracture rate for both vertebral and other fracture was significantly less in
      the post FLS patients, 36.5% versus 56% p-value = 0.01. CONCLUSION: FLS program
      benefited patients with fragility fractures by decreasing the incidence of all
      refracture rates.

PMID- 30274805
TI  - Transcranial direct current stimulation reduces secondary white-matter
      degradation after stroke.

PMID- 30274806
TI  - Native vitamin D in pre-dialysis chronic kidney disease.
AB  - Chronic kidney disease patients have a high prevalence of vitamin D
      insufficiency/deficiency. Vitamin D deficiency has been associated with a variety
      of bone, metabolic and cardiovascular disorders. However, the role of native
      vitamin D supplementation (ergocalciferol, cholecalciferol or calcifediol)
      remains unclear in chronic kidney disease (CKD), particularly in the pre-dialytic
      phase. Several international guidelines have been developed on CKD-Mineral and
      Bone Disorder, but the optimal strategy for native vitamin D supplementation and
      its clinical benefit remains a subject of debate in the scientific community.
      This paper aims to review the available literature, including randomized clinical
      trials that evaluated the effects of native vitamin D supplementation on pre
      dialysis CKD on biochemical and clinically relevant outcomes.

PMID- 30274807
TI  - The effects of pressure intervention on wound healing and scar formation in a
      Bama minipig model.
AB  - Pressure therapy has been widely used in clinical practice for the prevention or
      treatment of hypertrophic scars resulted from aberrations in wound healing.
      However, the precise molecular mechanisms of this process are only partially
      understood. In the present study, we established a Bama minipig model to observe
      the effect of pressure intervention on wound healing and scar formation.
      Transcriptome sequencing was performed to analyze the gene expression profiles in
      the injured and pressure-treated tissues. Furthermore, expression of the critical
      factors associated with IGF-1/IGF-1R pathways including PI3K/AKT and MEK/ERK and
      collagens were further analyzed by quantitative polymerase chain reaction (q-PCR)
      and Western blot. We observed that the mRNA expression of IGF-1 and IGF-1R were
      down-regulated in the pressure treated groups. Following pressure intervention,
      the trend in expression of PI3K/AKT decreased, whereas that of MEK/ERK expression
      increased, when quantified by q-PCR. Moreover, the level of PI3K protein
      expression decreased significantly after pressure treatment for one month but
      there was no significant difference in AKT protein expression. Interestingly, the
      trend in MEK/ERK protein expression was opposite to that indicated by q-PCR
      analysis. Furthermore, collagen I and III mRNA clearly declined after one month
      pressure treatment. Taken together, these results indicated that pressure
      intervention alleviated scar formation may via inhibiting the IGF-1/IGF-1R
      signaling pathway and collagen expression in the Bama minipig model.

PMID- 30274809
TI  - The effect of oral N-acetylcystein on prevention of extensive tissue destruction
      in electrical burn injury.
AB  - BACKGROUND: Electric burn patients usually suffer permanent injury and sequelae.
      Salvage of the zone of stasis is an important topic in the treatment of burn
      patients. N-Acetylcysteine (NAC), as an antioxidant, has effect on the saving
      zone of stasis and extensive rhabdomyolisis. The aim of this study was therefore
      to evaluate the effect of oral NAC on tissue destruction indicators in an
      electric burn rat model. MATERIAL AND METHODS: An experimental study was
      conducted with thirty six male Wistar albino rats divided into 2 groups. Group A
      (n=18) and group B (n=18) were electrical burn injury groups without and with NAC
      therapy, respectively. The extent of burn wounds were evaluated by planimetry
      using a digital wound measuring device. Blood samples were obtained to analyze
      creatine kinase (CK) levels as a marker of extensive rhabdomiolysis on the first
      hour after electric injury (baseline) and on the 7th day to see the antioxidant
      effect of NAC. RESULTS: A significant decrease in tissue destruction was seen by
      the necrotic area on day 7 in the NAC therapy group compared to the control group
      (mean 2.26+/-1.05cm2 versus mean 7.12+/-3.30cm2 respectively; p=0.001), which was
      confirmed by the level of serum CK (day 7: group A, mean 140+/-51U/L versus Group
      B, mean 102+/-6U/L; p=0.007). CONCLUSION: A decrease in electric burn necrotic
      area and tissue damage in the group using NAC treatment was demonstrated. NAC
      might have a beneficial effect in the treatment of electrical burns. Further
      experimental and clinical studies with NAC treatment are necessary to confirm
      these results.

PMID- 30274808
TI  - The time-course of the inflammatory response to major burn injury and its
      relation to organ failure and outcome.
AB  - Burn injury causes major inflammatory activation and cytokine release, however,
      the temporal resolution of the acute and sub-acute inflammatory response has not
      yet been fully delineated. To this end, we have quantified 20 inflammatory
      mediators in plasma from 44 adult patients 0-21 days after burn injury and
      related the time course of these mediators to % total body surface area (TBSA)
      burned, clinical parameters, organ failure and outcome. Of the cytokines analyzed
      in these patients, interleukin 6 (IL-6), IL-8, IL-10 and monocyte chemoattractant
      protein 1 (MCP-1) correlated to the size of the injury at 24-48h after burn
      injury. In our study, the concentration of IL-10 had prognostic value in patients
      with burn injury both measured at admission and at 24-48h after injury. However,
      simple demographic data such as age, % burned TBSA, inhalation injury and their
      combination, the Baux score and modified Baux score, outperform most of the
      cytokines, with the exception of IL-8 and MCP-1 levels on admission, in
      predicting death.

PMID- 30274810
TI  - Early clinical complete blood count changes in severe burn injuries.
AB  - INTRODUCTION: Following a severe burn injury, significant hematologic changes
      occur that are reflected in complete blood count (CBC) measurements. Our aim for
      this study was to examine trend in the components of the CBC in severely burned
      patients over the first week after injury and compare differences in CBC
      components between survivors and non-survivors. METHODS: A 5-year retrospective
      review was performed of adult (>=18years) burn patients with a TBSA>=15%. Age,
      TBSA, gender, mortality, length of hospital stay, ventilator days, and CBC were
      collected. RESULTS: Over the first week after injury, HBG and HCT decreased. This
      decrease was due to loss of red blood cells. WBC counts was initially elevated
      but decreased over the first 4days. PLT also decreased over the first 4days. Non
      survivors had lower HBG, HCT, RCC, and PLT over the first week compared to
      survivors. Non-survivors had higher WBC compared to survivors. RDW was elevated
      during the first week in non-survivors. MPV was elevated at the end of the first
      week in non-survivors and MPV on day 7 was independently associated with
      mortality (O.R. 2.01 (1.1-3.7)). Compared to survivors non-survivors received
      more transfusions of blood products during the first week after injury.
      CONCLUSION: Burn-injury specific trends in CBC measurements can be used as
      references to determine expected clinical course of burn patients. Non-survivors
      have early hematologic differences compared to survivors.

PMID- 30274811
TI  - Development and validity of the Burns-Child Adult Medical Procedure Interaction
      Scale (B-CAMPIS) for young children.
AB  - BACKGROUND: Young children are at increased risk of burn injury and of procedural
      distress during the subsequent wound care. There are currently few observational
      measures validated for use with young children during medical procedures. The aim
      of this research was to adapt the Child-Adult Medical Procedure Interaction Scale
      Revised (CAMPIS-R) to assess parent-young child interactions during burn wound
      care by including nonverbal behavioral coding. METHOD: Eighty-seven families of
      children (1-6years old) were recruited at their first burn dressing change.
      Potential behaviors were identified through a literature review, consulting
      health professionals, and direct observation of parents and children during burn
      wound care. Nonverbal behaviors were coded live, and verbal behaviors were audio
      recorded for later assessment. RESULTS: Inter-coder reliability was good to
      excellent for the Burns-CAMPIS (B-CAMPIS). The additional behaviors were
      correlated with the hypothesized coping, distress, coping-promoting and distress
      promoting categories of the CAMPIS-R. Some behaviors differed in frequency across
      child age groups, with older children demonstrating more verbal behaviors.
      Convergent validity was demonstrated through correlations with previously
      validated observational parent-child behavior measures, and parent- and nurse-
      reported measures of child pain and anxiety. Univariate regression analyses
      demonstrated the child categories of the B-CAMPIS accounted for equal or more of
      the variance of parent- and nurse- reported child pain and anxiety, compared to
      the CAMPIS-R. CONCLUSIONS: The B-CAMPIS is a reliable and valid measure, for
      assessing coping and distress relationships in young children and their families.
      Pending further validation, the B-CAMPIS assists researchers and clinicians to
      recognize and target important behaviors to improve young child coping during
      pediatric burn wound care.

PMID- 30274813
TI  - Planned enteral nutrition over-prescription to cover caloric and protein
      requirements in severely-ill burn patients.

PMID- 30274812
TI  - The trend of burn mortality in Iran - A study of fire, heat and hot substance
      related fatal injuries from 1990 to 2015.
AB  - INTRODUCTION: Burn injuries are a major cause of preventable mortality worldwide.
      To implement preventive strategies, a detailed understanding of the rate and
      trend of fatal burn injuries is needed. The aim of this study was to determine
      the rate and trend of burn mortality at national and province level in Iran from
      1990 to 2015. MATERIALS AND METHODS: The data were retrieved from various
      sources: the Death Registration System, cemetery databases, the Demographic and
      Health Survey and three national population and housing censuses. ICD-10 codes
      were converted to Global Burden of Disease (GBD) codes for comparability. After
      addressing the incompleteness of death data, statistical methods such as spatio
      temporal modelling and Gaussian Process Regression (GPR) were applied to estimate
      the levels and trend of death and cause specific mortality. RESULTS: The number
      of deaths due to burning across Iran was 80,625, with a male to female ratio of
      0.88, 0.94 and 1.14 in 1990, 1995 and 2015, respectively. The annual percentage
      change of age-standardized death rate from 1990 to 2015 was -5.42% and -4.22% in
      women and men, respectively. The burn-related age-standardized mortality rate
      decreased considerably from 5.97 in 1990 to 1.74 per 100,000 in 2015. The
      mortality rate due to burns was highest among those aged more than 85 years,
      especially in Ilam province. CONCLUSION: This study showed a decline in burn
      mortality in Iran from 1990 to 2015. Continued efforts to reduce the burden of
      burns are needed to accelerate this progress and prevent injuries.

PMID- 30274814
TI  - Epidemiology of work-related burn injuries presenting to burn centres in
      Australia and New Zealand.
AB  - BACKGROUND: Burn injuries to workers can have a devastating impact, however
      knowledge of the epidemiology of work-related burn injuries in Australia and New
      Zealand is limited. PURPOSE: To describe epidemiological characteristics of work
      related burn injuries in Australia and New Zealand, and to compare these with non
      work-related burns. METHODS: Adult burn injury data, 2009-2016, were extracted
      from the Burns Registry of Australia and New Zealand. Descriptive statistics were
      used to describe demographic, injury, management and outcome characteristics.
      Differences between work-related and non-work-related injuries were assessed
      using Chi-square and Wilcoxon rank-sum tests. RESULTS: Of 10,574 adult patients
      treated in burn centres in Australia and New Zealand, 2009-2016, 17% had work
      related burns. Most work-related cases were male (85%), less than 35 years old
      (53%), and had sustained flame (33%), scald (30%) or chemicals (17%) burns.
      Proportions of chemical, scald and electrical burns were greater for work-related
      than for non-work-related burns, with this being most marked for chemical and
      electrical burns (17% vs. 3% and 7% vs. 1%, respectively). CONCLUSIONS: Almost
      one in five cases of working-aged people admitted to Australian and New Zealand
      burns centres was work-related. Through identification of vulnerable groups, this
      study informs policy and strategies to minimise occupational burn risk.

PMID- 30274815
TI  - Locked-in syndrome following meningitis with brainstem abscess.

PMID- 30274816
TI  - Foreword. History of the frontal lobe.

PMID- 30274817
TI  - An unexpected diagnosis: leukaemic presentation of blastic plasmacytoid dendritic
      cell neoplasm with massive splenomegaly.

PMID- 30274818
TI  - Immunizations 2018: don't ask...just tell.

PMID- 30274820
TI  - Non-invasive and accurate diagnostic system for biliary atresia.

PMID- 30274819
TI  - Functional validation of the albinism-associated tyrosinase T373K SNP by
      CRISPR/Cas9-mediated homology-directed repair (HDR) in rabbits.
AB  - BACKGROUND: Oculocutaneous albinism (OCA) is a group of autosomal recessive
      disorders characterized by reduced melanin that are caused by mutations in the
      gene encoding tyrosinase (TYR), which is the rate-limiting enzyme in the
      production of the pigment melanin. Many studies or meta-analyses have suggested
      an association between the TYR T373K SNP and OCA1, but there is limited
      biochemical and genetic evidence to support this association. METHODS: We
      overexpressed TYR-WT and TYR-T373K mutants on HK293T cells and tested the changes
      of melanin production and tyrosinase activity. Then we generated TYR-K373T knock
      in (KI) rabbits by microinjection of ssDNA and synthesized RNAs targeting C1118A
      using CRISPR/Cas9-HDR to observe the formation of melanin. FINDINGS: We
      demonstrated that the T373K mutation in TYR can reduce tyrosinase activity,
      leading to an absence of melanin synthesis at the cell-level. The gene-edited TYR
      K373T rabbits exhibited rescued melanin production in hair follicles and irises,
      as inferred from the evident decrease in pigmentation in TYR-T373K rabbits, thus
      providing functional validation of the albinism-associated T373K SNP at the
      animal level. INTERPRETATION: Our study provides the first animal-level
      functional validation of the albinism-associated TYR K373T SNP in rabbits, and
      these results will facilitate gene therapy of OCA1 in pre-clinical settings in
      the future. FUND: The National Key Research and Development Program of China Stem
      Cell and Translational Research, the Strategic Priority Research Program of the
      Chinese Academy of Sciences, the Guangdong Province Science and Technology Plan
      Project, and the Program for JLU Science and Technology Innovative Research Team.

PMID- 30274821
TI  - Synergistic effect of Nutlin-3 combined with MG-132 on schwannoma cells through
      restoration of merlin and p53 tumour suppressors.
AB  - BACKGROUND: The great majority of sporadic vestibular schwannomas (VSs) are due
      to the mutations of the NF2 gene encoding merlin. Sporadic VSs exhibit variable
      growth patterns and only a small fraction of the tumours are fast-growing;
      however, the underlying mechanisms remain undefined. METHODS: DNA sequencing and
      dosage analysis were used to identify the NF2 mutation status in sporadic
      schwannomas. The expression and sub-cellular localization of merlin and p53-MDM2
      were assessed by immunoblotting, qRT-PCR and immunofluorescence. In vitro and in
      vivo studies were performed to reveal the effects of Nutlin-3 (a MDM2 inhibitor)
      and/or MG-132(a proteasome inhibitor) on schwannomas. The proliferation of
      schwannoma cells was assessed by CCK-8 assay, EdU staining and Flow cytometry
      analysis. FINDINGS: Double genetic hits of NF2 tended to occur in fast-growing
      tumours, characterized by the absence of merlin. The deregulation of p53-MDM2 was
      demonstrated to mediate merlin-deficient tumour growth, characterized by a
      nuclear accumulation of stabilized MDM2, contributing to a nuclear export of p53
      for degradation. Nutlin-3 blocked the proliferation of schwannoma cells via a
      cooperative recovery of merlin and p53, accompanied by the shuttling of both
      proteins from the cytoplasm to the nucleus. We further demonstrated a difference
      in the sensitivity to Nutlin-3 between schwannoma cells with and without merlin
      expression. Nutlin-3 combined with MG-132 narrowed this between-group difference
      and triggered stronger inhibitory effects on the growth of schwannomas through
      coordinated reactivation of p53. INTERPRETATION: These findings present treatment
      strategies directed on the pathogenesis of sporadic schwannomas. FUND: National
      Natural Science Foundation of China.

PMID- 30274822
TI  - Exhaustive non-synonymous variants functionality prediction enables high
      resolution characterization of the neurofibromin architecture.
AB  - BACKGROUND: Neurofibromatosis type I (NF1) is caused by heterozygous loss-of
      function variants in the NF1 gene encoding neurofibromin which serves as a tumor
      suppressor that inhibits RAS signaling and regulates cell proliferation and
      differentiation. While, the only well-established functional domain in the NF1
      protein is the GAP-related domain (GRD), most of the identified non-truncating
      disease-causing variants are located outside of this domain, supporting the
      existence of other important disease-associated domains. Identifying these
      domains may reveal novel functions of NF1. METHODS: By implementing inferential
      statistics combined with machine-learning methods, we developed a novel NF1
      specific functional prediction model that focuses on nonsynonymous single
      nucleotide variants (SNVs). The model enables annotating all possible NF1
      nonsynonymous variants, thus mapping the range of pathogenic non-truncating
      variants at the codon level across the NF1 gene. FINDINGS: The generated model
      demonstrates high absolute prediction value for missense and splice-site
      variations (area under the ROC curve of 0.96) outperforming 14 other established
      models. By reviewing the entire dataset of nonsynonymous variants, two novel
      domains (Armadillo type fold 1 and 2) were identified as being associated with
      pathogenicity (OR 1.86; CI 1.04 to 3.34 and OR 2.08; CI 1.08 to 4.04,
      respectively; P < .05). Specific exons and codons associated with increased
      pathogenicity were also detected along the gene inside and outside the GRD
      domain. INTERPRETATION: The developed model, enabled better prediction of
      pathogenicity for variants in NF1 gene, as well as elucidation of novel NF1
      associated domains in addition to the GRD. FUND: This work was partially
      supported by the Kahn foundation. DGE is supported by the all Manchester NIHR
      Biomedical Research Centre (IS-brC-1215-20007).

PMID- 30274823
TI  - Epidemiological and clinical characteristics of Dientamoeba fragilis infection.
AB  - INTRODUCTION: The characteristics of D. fragilis infection are described, with
      special focus on the clinical and epidemiological aspects. MATERIALS AND METHODS:
      A retrospective and descriptive study was performed, including all the patients
      with Dientamoeba fragilis infection who attended a specialized unit between
      January 2012 and December 2017. PCR was used to diagnose D. fragilis. Patients
      were treated with metronidazole or paromomycin and reviewed at four and eight
      weeks post-treatment. Cure was defined as the negativization of all
      parasitological tests, in absence of symptoms. RESULTS: 163 patients were
      diagnosed. The most frequent symptoms were abdominal pain (36.2%), chronic
      diarrhoea (12.3%), anal itching (10.4%), abdominal discomfort (9.2%), skin
      disease (8%), acute diarrhoea (4.3%) and vomiting (4.3%). Fifty patients were
      asymptomatic. Forty-two patients had eosinophilia in blood. Thirty-eight cases
      (23.3%) had a coinfection by Enterobius vermicularis. One hundred and seven
      patients received treatment, sixty-one of them with metronidazole and the rest
      with paromomycin. Ninety-nine patients (91%) were cured. The rate of cure was
      100% in the paromomycin group versus 86.8% in the metronidazole group (p=0.005;
      OR: 1.173 [1.057-1.302]). The absence of cure was associated with E. vermicularis
      coinfection (p=0.014; OR: 6.167 [1.432-26.563] and with longer duration of the
      symptoms (175 [+/-159SD]) versus 84 [+/-88SD] days, p=0.014) but multivariable
      analysis did not confirm these associations. CONCLUSION: Dientamoeba fragilis is
      an important and underestimated cause of gastrointestinal disease in both the
      autochthonous and immigrant or traveller population. More studies are needed to
      clarify its optimal treatment and the role played by E. vermicularis in its
      transmission and maintenance.

PMID- 30274824
TI  - Endogenous IL-10 maintains immune tolerance but IL-10 gene transfer exacerbates
      autoimmune cholangitis.
AB  - The immunomodulatory effect of IL-10 as an immunosuppressive and anti
      inflammatory cytokine is well known. Taking advantage of our established mouse
      model of autoimmune cholangitis using 2-octynoic acid conjugated ovalbumin (2-OA
      OVA) induction, we compared liver pathology, immune cell populations and
      antimitochondrial antibodies between IL-10 knockout and wild type mice immunized
      with 2-OA-OVA. At 10 weeks post immunization, portal inflammation and fibrosis
      were more severe in 2-OA-OVA immunized IL-10 knockout mice than in wild type
      mice. This was accompanied by significant higher levels of collagen I and III
      expression, T, NK and NKT subsets in liver and IgG anti-mitochondrial
      autoantibodies (AMAs) compared to 2-OA-OVA immunized wild type mice, suggesting
      that endogenous IL-10 is necessary for the maintenance of immune tolerance in
      primary biliary cholangitis (PBC). Further, we investigated whether
      administration of exogenous IL-10 could prevent PBC by administration of IL-10
      expressing recombinant adeno-associated virus (AAV-IL-10) either 3 days before or
      3 weeks after the establishment of liver pathology. Interestingly, administration
      of AAV-IL-10 resulted in increased liver inflammation and fibrosis, accompanied
      by increases in IFN-gamma in liver CD4+ T cell, granzyme B, FasL, and CD107a in
      liver CD8+ T and NKT cells, and granzyme B and FasL in liver NK cells of AAV-IL
      10 administered mice compared with control mice. Furthermore, administration of
      AAV-IL-10 significantly increased levels of proinflammatory cytokines and
      chemokines (IFN-gamma, TNF-alpha, CXCL9 and CXCL10) and collagen I and III
      production in naive mice, together with increase in immune cell infiltration and
      collagen deposition in the liver, suggesting a role of IL-10 in fibrosis. In
      conclusion, our data demonstrate that endogenous IL-10 is critical in the
      maintenance of immune tolerance but exogenous administration of IL-10 exacerbates
      liver inflammation and fibrosis. Furthermore, the distinctive presence of
      inflammatory immune cell populations and collagen expression in AAV-IL-10 treated
      naive mice cautions against the clinical use of exogenous IL-10 in patients with
      autoimmune cholangitis.

PMID- 30274825
TI  - Gastrointestinal bleeding following transduodenal endoscopic ultrasound-guided
      gallbladder drainage.

PMID- 30274827
TI  - ABCG2 rs2231142 (Q141K) and oxypurinol concentrations in people with gout
      receiving allopurinol.

PMID- 30274826
TI  - Malignant and pre-malignant colorectal lesions in forty-year olds: Is earlier
      inception of screening warranted?

PMID- 30274828
TI  - The dentin permeability of anti-inflammatory and antibacterial drugs: In vitro
      study.
AB  - BACKGROUND/PURPOSE: Stimuli from the oral cavity may penetrate through exposed
      dentinal tubules and evoke inflammatory pulp response. Anti-bacterial and anti
      inflammatory drugs applied to exposed dentin may infiltrate through the dentinal
      tubules and cause pulp recovery. This study investigated the dentin permeability
      of anti-bacterial and anti-inflammation drugs via an in-vitro transwell dentin
      disc tube model. METHODS: Twenty-seven dentin discs prepared from extracted human
      molars were collected. Nine kinds of drugs were investigated with three dentin
      discs in each group. These nine drugs included two anti-bacterial drugs
      (ampicillin sodium and clindamycin phosphate), two corticosteroids (betamethasone
      sodium phosphate and hydrocortisone sodium succinate), three non-steroidal anti
      inflammatory drugs (NSAIDs, piroxicam, lysine acetylsalicylate, and diclofenac
      sodium), and two natural extracts with anti-inflammatory effect (Ginsenoside Rg1
      and Hinokitol). The drugs were introduced to the transwell dentin disc tube model
      and the 4-hour cumulative release of the drug was detected and recorded by UV
      visible spectroscopy. RESULTS: We found that ampicilin sodium had better dentin
      permeability than clindamycin phosphate. Betamethasone sodium phosphate revealed
      better dentin permeability than hydrocortisone sodium succinate. Lysine
      acetylsalicylate showed the best dentin permeability among the three NSAIDs.
      Ginsenoside Rg1 had the best dentin permeability among the nine drugs tested.
      However, Hinokitiol could not penetrate the dentin disc after 4 h. CONCLUSION:
      Regarding the dentin permeability, Ginsenoside Rg1 is the best among the seven
      anti-inflammatory drugs tested and ampicilin sodium is the better one between the
      two anti-bacterial drugs tested. Therefore, these two drugs may have high
      potential for treating exposed dentinal tubule diseases.

PMID- 30274829
TI  - A Hidden Markov Model for Detecting Confinement in Single-Particle Tracking
      Trajectories.
AB  - State-of-the-art single-particle tracking (SPT) techniques can generate long
      trajectories with high temporal and spatial resolution. This offers the
      possibility of mechanistically interpreting particle movements and behavior in
      membranes. To this end, a number of statistical techniques have been developed
      that partition SPT trajectories into states with distinct diffusion signatures,
      allowing a statistical analysis of diffusion state dynamics and switching
      behavior. Here, we develop a confinement model, within a hidden Markov framework,
      that switches between phases of free diffusion and confinement in a harmonic
      potential well. By using a Markov chain Monte Carlo algorithm to fit this model,
      automated partitioning of individual SPT trajectories into these two phases is
      achieved, which allows us to analyze confinement events. We demonstrate the
      utility of this algorithm on a previously published interferometric scattering
      microscopy data set, in which gold-nanoparticle-tagged ganglioside GM1 lipids
      were tracked in model membranes. We performed a comprehensive analysis of
      confinement events, demonstrating that there is heterogeneity in the lifetime,
      shape, and size of events, with confinement size and shape being highly conserved
      within trajectories. Our observations suggest that heterogeneity in confinement
      events is caused by both individual nanoparticle characteristics and the binding
      site environment. The individual nanoparticle heterogeneity ultimately limits the
      ability of interferometric scattering microscopy to resolve molecule dynamics to
      the order of the tag size; homogeneous tags could potentially allow the
      resolution to be taken below this limit by deconvolution methods. In a wider
      context, the presented harmonic potential well confinement model has the
      potential to detect and characterize a wide variety of biological phenomena, such
      as hop diffusion, receptor clustering, and lipid rafts.

PMID- 30274830
TI  - Sphingomyelin Stereoisomers Reveal That Homophilic Interactions Cause Nanodomain
      Formation.
AB  - Sphingomyelin is an abundant lipid in some cellular membrane domains, such as
      lipid rafts. Hydrogen bonding and hydrophobic interactions of the lipid with
      surrounding components such as neighboring sphingomyelin and cholesterol (Cho)
      are widely considered to stabilize the raft-like liquid-ordered (Lo) domains in
      membrane bilayers. However, details of their interactions responsible for the
      formation of Lo domains remain largely unknown. In this study, the enantiomer of
      stearoyl sphingomyelin (ent-SSM) was prepared, and its physicochemical properties
      were compared with the natural SSM and the diastereomer of SSM to examine
      possible stereoselective lipid-lipid interactions. Interestingly, differential
      scanning calorimetry experiments demonstrated that palmitoyl sphingomyelin, with
      natural stereochemistry, exhibited higher miscibility with SSM bilayers than with
      ent-SSM bilayers, indicating that the homophilic sphingomyelin interactions
      occurred in a stereoselective manner. Solid-state 2H NMR revealed that Cho
      elicited its ordering effect very similarly on SSM and ent-SSM (and even on the
      diastereomer of SSM), suggesting that SSM-Cho interactions are not significantly
      affected by stereospecific hydrogen bonding. SSM and ent-SSM formed gel-like
      domains with very similar lateral packing in SSM/Cho/palmitoyloleoyl
      phosphatidylcholine membranes, as shown by fluorescence lifetime experiments.
      This observation can be explained by a homophilic hydrogen-bond network, which
      was largely responsible for the formation of gel-like nanodomains of SSMs (or ent
      SSM). Our previous study revealed that Cho-poor gel-like domains contributed
      significantly to the formation of an Lo phase in sphingomyelin/Cho membranes. The
      results of the study presented here further show that SSM-SSM interactions occur
      near the headgroup region, whereas hydrophobic SSM-Cho interactions appeared
      important in the bilayer interior for Lo domain formation. The homophilic
      interactions of sphingomyelins could be mainly responsible for the formation of
      the domains of nanometer size, which may correspond to the small
      sphingomyelin/Cho-based rafts that temporally occur in biological membranes.

PMID- 30274831
TI  - Diffusion of Exit Sites on the Endoplasmic Reticulum: A Random Walk on a
      Shivering Backbone.
AB  - Major parts of the endoplasmic reticulum (ER) in eukaryotic cells are organized
      as a dynamic network of membrane tubules connected by three-way junctions. On
      this network, self-assembled membrane domains, called ER exit sites (ERES),
      provide platforms at which nascent cargo proteins are packaged into vesicular
      carriers for subsequent transport along the secretory pathway. Although ERES
      appear stationary and spatially confined on long timescales, we show here via
      single-particle tracking that they exhibit a microtubule-dependent and
      heterogeneous anomalous diffusion behavior on short and intermediate timescales.
      By quantifying key parameters of their random walk, we show that the subdiffusive
      motion of ERES is distinct from that of ER junctions, i.e., ERES are not tied to
      junctions but rather are mobile on ER tubules. We complement and corroborate our
      experimental findings with model simulations that also indicate that ERES are not
      actively moved by microtubules. Altogether, our study shows that ERES perform a
      random walk on the shivering ER backbone, indirectly powered by microtubular
      activity. Similar phenomena can be expected for other domains on subcellular
      structures, setting a caveat for the interpretation of domain-tracking data.

PMID- 30274772
TI  - Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of
      undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS
      trial.
AB  - BACKGROUND: Patent foramen ovale (PFO) is a contributor to embolic stroke of
      undetermined source (ESUS). Subgroup analyses from previous studies suggest that
      anticoagulation could reduce recurrent stroke compared with antiplatelet therapy.
      We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa
      inhibitor, would reduce the risk of recurrent ischaemic stroke compared with
      aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. METHODS:
      NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres
      in 31 countries that assessed the efficacy and safety of rivaroxaban versus
      aspirin for secondary stroke prevention in patients with ESUS. For this
      prespecified subgroup analysis, cohorts with and without PFO were defined on the
      basis of transthoracic echocardiography (TTE) and transoesophageal
      echocardiography (TOE). The primary efficacy outcome was time to recurrent
      ischaemic stroke between treatment groups. The primary safety outcome was major
      bleeding, according to the criteria of the International Society of Thrombosis
      and Haemostasis. The primary analyses were based on the intention-to-treat
      population. Additionally, we did a systematic review and random-effects meta
      analysis of studies in which patients with cryptogenic stroke and PFO were
      randomly assigned to receive anticoagulant or antiplatelet therapy. FINDINGS:
      Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and
      assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were
      followed up for a mean of 11 months because of early trial termination. PFO was
      reported as present in 534 (7.4%) patients on the basis of either TTE or TOE.
      Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke
      rate of 4.8 events per 100 person-years compared with 2.6 events per 100 person
      years in those treated with rivaroxaban. Among patients with known PFO, there was
      insufficient evidence to support a difference in risk of recurrent ischaemic
      stroke between rivaroxaban and aspirin (hazard ratio [HR] 0.54; 95% CI 0.22
      1.36), and the risk was similar for those without known PFO (1.06; 0.84-1.33;
      pinteraction=0.18). The risks of major bleeding with rivaroxaban versus aspirin
      were similar in patients with PFO detected (HR 2.05; 95% CI 0.51-8.18) and in
      those without PFO detected (HR 2.82; 95% CI 1.69-4.70; pinteraction=0.68). The
      random-effects meta-analysis combined data from NAVIGATE ESUS with data from two
      previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0.48 (95%
      CI 0.24-0.96; p=0.04) for ischaemic stroke in favour of anticoagulation, without
      evidence of heterogeneity. INTERPRETATION: Among patients with ESUS who have PFO,
      anticoagulation might reduce the risk of recurrent stroke by about half, although
      substantial imprecision remains. Dedicated trials of anticoagulation versus
      antiplatelet therapy or PFO closure, or both, are warranted. FUNDING: Bayer and
      Janssen.

PMID- 30274833
TI  - Local Tension on Talin in Focal Adhesions Correlates with F-Actin Alignment at
      the Nanometer Scale.
AB  - Cellular force transmission and mechanotransduction are critical in
      embryogenesis, normal physiology, and many diseases. Talin plays a key role in
      these processes by linking integrins to force-generating actomyosin. Using the
      previously characterized FRET-based talin tension sensor, we observed variations
      of tension both between and within individual focal adhesions in the same cell.
      Assembling and sliding adhesions showed gradients with higher talin tension
      toward the cell center, whereas mature, stable adhesions had uniform talin
      tension. Total talin accumulation was maximal in high-tension regions; by
      contrast, vinculin intensity was flat or maximal at the adhesion center, and
      actin intensity was maximal toward the cell center. To investigate mechanism, we
      combined talin tension imaging with cellular cryotomography to visualize the
      correlated actin organization at nanometer resolution. Regions of high talin
      tension had highly aligned linear actin filaments, whereas regions of low tension
      had less-well-aligned F-actin. These results reveal an orchestrated
      spatiotemporal relationship between talin tension, actin/vinculin localization,
      local actin organization, and focal adhesion dynamics.

PMID- 30274832
TI  - Bioenergetic Feedback between Heart Cell Contractile Machinery and Mitochondrial
      3D Deformations.
AB  - In the heart, mitochondria are arranged in pairs sandwiched between the
      contractile machinery, which is the major ATP consumer. Thus, in response to the
      contraction-relaxation cycle of the cell, the mitochondrial membrane should
      deform accordingly. Membrane deformations in isolated ATP synthesis or in
      isolated mitochondria affect ATP production. However, it is unknown whether
      physiological deformation of the mitochondrial membrane in response to the
      contraction-relaxation cycle can act as a bioenergetic signaling mechanism
      between ATP demand to supply. We used both experimental and computational tools
      to reveal whether bioenergetic feedback exists between heart cell contractile
      machinery and mitochondrial three-dimensional (3D) deformations. We measured the
      mitochondrial 3D deformation in contracting rabbit cardiac myocytes and used
      published data on rat cardiac myocytes. These measurements were an input to a
      novel biophysics model that includes a description of ionic molecules on the
      mitochondrial membrane, Ca2+ cycling, and mitochondrial membrane stress. As is
      the case for rat cardiomyocytes, in rabbit cardiomyocytes, the mitochondrial
      length contracted and expanded with a similar dynamic as the sarcomere length. In
      contrast, the mitochondrial width expanded and then contracted with a similar
      dynamic as the mitochondrial length. Differences in the extent of deformation and
      fractional deformation between the width- and thick-axes were quantified and
      interpreted as the degree anisotropy between those respective axes. Finally, the
      model predicts that significant bioenergetic feedback between heart cell
      contractile machinery and mitochondrial 3D deformations does exist in unloaded
      rabbit and rat cells. However, this feedback is not a dominant mechanism in ATP
      supply to demand matching.

PMID- 30274835
TI  - HCV core antigen: toward elimination of nucleic acid testing?

PMID- 30274836
TI  - Correction to Lancet Gastroenterol Hepatol 2018; published online Sept 24.
      http://dx.doi.org/10.1016/S2468-1253(18)30269-3.

PMID- 30274837
TI  - Extraordinary Altruism and Transcending the Self.
AB  - Longstanding psychological theories posit a link between empathy and altruism. A
      new study of anonymous kidney donors finds these 'extraordinary altruists' show
      an increased overlap in neural responses to pain for self and others. These
      findings, alongside other recent studies of altruism, shed new light on the
      nature of selflessness.

PMID- 30274838
TI  - Expression of IL-3 receptors and impact of IL-3 on human T and B cells.
AB  - A large number of animal models revealed that IL-3 plays an important role for
      the development of T and B cell-mediated autoimmune diseases. However, little is
      known about the expression and regulation of IL-3 receptors in human T and B
      cells and how IL-3 modulates the activation and survival of these cells. We show
      that the IL-3 receptor CD123 is substantially upregulated on proliferating CD4+
      and CD8+ T as well as B cells. Upregulation of CD123 differs between various
      activators and can be further modulated by cytokines. Exposure of human T and B
      cells to IL-3 enhances proliferation and survival. IL-3 also induces a shift
      towards secretion of proinflammatory cytokines in T and B cells and reduces the
      expression of IL-10 in B cells. Thus IL-3 may have proinflammatory and
      immunostimulatory properties also in human autoimmune diseases.

PMID- 30274834
TI  - HCV core antigen as an alternative to HCV RNA testing in the era of direct-acting
      antivirals: retrospective screening and diagnostic cohort studies.
AB  - BACKGROUND: Direct-acting antivirals for chronic hepatitis C (HCV) infection have
      reduced the need for on-treatment HCV RNA monitoring. We assessed the accuracy
      and cost implications of using HCV core antigen testing to replace HCV RNA
      testing for confirmation of diagnosis, on-treatment monitoring, and determination
      of sustained virological response (SVR). METHODS: In a retrospective screening
      cohort study, de-identified residual serum from unselected samples were obtained
      from commercial laboratories in Ontario, Canada. Samples from each 5-year age-sex
      band from birth years 1945-74 collected from Aug 1, 2014, to Feb 28, 2015, were
      included. All samples that tested positive for HCV antibodies, and 10% of samples
      that tested negative for HCV antibodies, were tested for HCV core antigen and HCV
      RNA. A retrospective clinical cohort study was also done using blood samples from
      patients with confirmed HCV infection collected at four tertiary academic
      centres: one in Canada, two in Germany, and one in the USA. For assessment of
      SVR, we included samples from patients who started direct-acting antiviral-based
      treatment (excluding telaprevir and boceprevir) with or without peginterferon,
      ribavirin, or both, from Jan 1, 2014, to March 31, 2015. To ensure inclusion of
      adequate numbers for analysis, patients who relapsed after any treatment regimen
      were included. Serum samples included in the study were from baseline, week 4 on
      treatment (only for patients treated with direct-acting antivirals), end of
      treatment, and week 12 or 24 of follow-up. The sensitivity and specificity of
      core antigen testing as a diagnostic tool was assessed in the screening cohort,
      using HCV RNA as a reference. The sensitivity and specificity of core antigen
      testing as well as its concordance with HCV RNA testing in the clinical cohort
      was assessed at baseline, week 4 on-treatment, and at weeks 12 or 24 after the
      end of treatment in patients undergoing therapy with direct-acting antivirals.
      The cost-effectiveness of core antigen testing with and without confirmatory HCV
      RNA testing for negative samples was also assessed. FINDINGS: From 10 006 samples
      in the screening cohort, 75 of 80 viraemic (HCV RNA-positive) samples tested
      positive for HCV core antigen (sensitivity 94%, 95% CI 86-98), and none of the
      993 HCV RNA-negative samples tested positive for HCV core antigen (specificity
      100%, 95% CI 94-100). The five viraemic samples that tested negative for HCV core
      antigen had low corresponding HCV RNA concentrations. In the clinical cohort, two
      (1%) of 202 baseline samples tested negative for HCV core antigen; one had a low
      HCV RNA concentration (468 IU/mL), the other had a high HCV RNA concentration (>2
      000 000 IU/mL). By week 4 of treatment, HCV core antigen concentrations decreased
      in all patients but were not predictive of SVR. Although there was good
      concordance between HCV RNA and HCV core antigen results at 12 weeks after the
      end of treatment (r=0.97; p<0.0001), three of the 148 patients who achieved SVR
      at 12 weeks tested HCV core antigen positive. 12 weeks after the end of
      treatment, HCV core antigen was undetectable in one (1%) of 71 samples from
      patients who were identified as having relapsed according to HCV RNA detection.
      On-treatment and end-of-treatment testing of core antigen or HCV RNA provided
      little clinical value. The use of HCV core antigen testing as a confirmatory
      diagnostic strategy was cost saving relative to HCV RNA testing, with a reduction
      of CAD$0.29-3.70 per patient screened depending on whether HCV RNA testing was
      used to confirm HCV core antigen-negative results. INTERPRETATION: These data
      support the use of HCV core antigen testing to document HCV viraemia in a cost
      saving diagnostic algorithm. In a treatment setting, HCV core antigen testing can
      be used instead of HCV RNA testing for diagnosis and documentation of treatment
      adherence, but it might not be adequate to determine SVR. This approach might
      improve access to care, particularly in low-income and middle-income countries.
      FUNDING: Abbott Diagnostics and Toronto Centre for Liver Disease.

PMID- 30274839
TI  - Glycan recognition at the saliva - oral microbiome interface.
AB  - The mouth is a first critical interface where most potentially harmful substances
      or pathogens contact the host environment. Adaptive and innate immune defense
      mechanisms are established there to inactivate or eliminate pathogenic microbes
      that traverse the oral environment on the way to their target organs and tissues.
      Protein and glycoprotein components of saliva play a particularly important role
      in modulating the oral microbiota and helping with the clearance of pathogens. It
      has long been acknowledged that glycobiological and glycoimmunological aspects
      play a pivotal role in oral host-microbe, microbe-host, and microbe-microbe
      interactions in the mouth. In this review, we aim to delineate how glycan
      mediated host defense mechanisms in the oral cavity support human health. We will
      describe the role of glycans attached to large molecular size salivary
      glycoproteins which act as a first line of primordial host defense in the human
      mouth. We will further discuss how glycan recognition contributes to both
      colonization and clearance of oral microbes.

PMID- 30274841
TI  - Paravalvular leaks in valve replacement: Do we need to blow the whistle?

PMID- 30274840
TI  - Cytocompatibility and mechanical properties of surgical sealants for
      cardiovascular applications.
AB  - OBJECTIVES: The present study compared physical, mechanical, and biologic
      characteristics of 4 clinically available surgical sealants for cardiovascular
      repair. METHODS: BioGlue (Cryolife Inc, Kennesaw, Ga), PreveLeak (Mallinckrodt
      Pharmaceuticals, St Louis, Mo), Tridyne VS (BD, Franklin Lakes, NJ), and Coseal
      (Baxter Healthcare Corporation, Westlake Village, Calif) were compared for the
      following properties: hydrated swelling, cytocompatibility, burst strength,
      biaxial stretching (elasticity), and in vitro degradation. RESULTS: Sealants
      showed a wide range of swelling upon hydration. By gravimetric and volumetric
      measurement, swelling was greatest for Coseal followed by Tridyne VS, BioGlue,
      and PreveLeak. Tridyne VS was the most cytocompatible based on Alamar Blue assay
      results, supporting 85% cell survival compared with 36% to 39% survival with the
      other sealants. All sealants withstood pressure above mean arterial pressure (70
      110 mm Hg) and physiologic systolic blood pressure (90-140 mm Hg) in an ex vivo
      arterial flow burst model; lowest peak pressure at failure was PreveLeak at 235
      +/- 48 mm Hg, and highest peak pressure at failure was BioGlue at 596 +/- 72 mm
      Hg. Biaxial tensile testing showed no differences in elasticity between ex vivo
      porcine aorta and carotid arteries and Tridyne VS or Coseal, and BioGlue and
      PreveLeak were significantly stiffer. In vitro degradation time for Coseal was 6
      days and 21 days for Tridyne VS. No degradation was observed in BioGlue or
      PreveLeak for 30 days. CONCLUSIONS: Although all sealants withstood
      supraphysiologic arterial pressure, there were differences in characteristics
      that may be important in clinical outcome. Coseal degradation time was short
      compared with other sealants, whereas BioGlue and PreveLeak showed a significant
      compliance mismatch with native porcine carotid artery. Tridyne VS was
      significantly more cytocompatible than the other 3 sealants.

PMID- 30274842
TI  - Atypical endophthalmitis after intraocular collamer lens implantation.
AB  - Unilateral endophthalmitis occurred after bilateral immediately sequential
      intraocular collamer lens (Visian Implantable Collamer Lens) implantation for the
      correction of myopic astigmatism in a 49-year-old woman. The surgeries and
      initial recovery were unremarkable. However, after 3 days, the patient noticed
      increasing blurring of vision in the left eye and presented to our clinic. The
      anterior segment of this eye was quiet, while the vitreous cavity was densely
      infiltrated. Immediate explantation of the corrective lens and vitrectomy
      combined with intravitreal antibiotic injection were performed. Staphylococcus
      epidermidis was detected in the vitreous tap and treated with intravenous
      antibiotics, antibiotic eyedrops, and parabulbar injections of dexamethasone. The
      corrected distance visual acuity recovered to 20/20 over a 6-month period.
      However, a cataract developed thereafter.

PMID- 30274843
TI  - Analysis of corneal higher-order aberrations in cataract patients with high
      myopia.
AB  - PURPOSE: To evaluate the differences in corneal higher-order aberrations (HOAs)
      between cataract patients with high axial myopia and normal cataract patients,
      and to identify the associated factors. SETTING: Department of Ophthalmology and
      Vision Science of the Eye and ENT Hospital of Fudan University, Shanghai, China.
      DESIGN: Retrospective case series. METHODS: Corneal aberrations and axial lengths
      (ALs) were measured using a rotating Scheimpflug camera (Pentacam) and partial
      coherence interferometry (IOLMaster) in the high myopia group and the control
      group. RESULTS: The study comprised 287 patients (520 eyes). There were 194 eyes
      in the high myopia group and 326 eyes in the control group. The 5 anterior
      corneal aberrations-vertical coma, vertical trefoil, horizontal coma, oblique
      trefoil, and primary spherical aberration-in the high myopia group were 0.07 MUm
      +/- 0.38 (SD), -0.11 +/- 0.23 MUm, 0.07 +/- 0.28 MUm, -0.02 +/- 0.18 MUm, and
      0.39 +/- 0.19 MUm, respectively. No negative primary spherical aberrations of the
      total or anterior corneal surface were found in the high myopia group.
      Differences between the 2 groups were found in terms of central corneal
      thickness, astigmatism, primary spherical aberration, vertical coma, and oblique
      trefoil; however, these differences were not consistent between different age
      subgroups. Higher-order aberrations were correlated with age. Posterior corneal
      vertical coma was correlated with AL (Pearson correlation = -0.188, P = .047).
      CONCLUSIONS: Negative primary spherical aberrations of the anterior or total
      corneal surface were not found in the high myopia group. Age showed a strong
      relationship with HOAs. For cataract patients with high myopia, aspheric
      intraocular lens implantation is recommended.

PMID- 30274844
TI  - Third- and fourth-generation formulas for intraocular lens power calculation
      before and after phakic intraocular lens insertion in high myopia.
AB  - PURPOSE: To determine the effect of Visian Implantable Collamer Lens phakic
      intraocular lens (pIOL) insertion on biometric parameters and IOL power
      calculation. SETTING: Beirut Eye and ENT Specialist Hospital, Beirut, Lebanon.
      DESIGN: Prospective case series. METHODS: The IOLMaster 500 biometer was used to
      measure axial length (AL), keratometry (K), and anterior chamber depth (ACD)
      values before and 2 months after pIOL implantation. The IOL power was calculated
      using third-generation formulas (SRK/T, Holladay 1, Hoffer Q) and fourth
      generation formulas (Haigis, Barrett Universal II). RESULTS: The study comprised
      24 eyes (12 patients). The preoperative and postoperative AL were comparable
      (27.35 mm +/- 1.51 [SD] versus 27.36 +/- 1.6 mm; P = .91), as were the K values.
      There was a significant difference between the preoperative and postoperative ACD
      (3.67 +/- 0.46 mm versus 3.4 +/- 0.56 mm; P = .008). The mean IOL power
      calculation did not change significantly using the Haigis (10.04 +/- 3.42
      diopters [D] versus 10.1 +/- 3.59 D; P = .69), SRK/T (9.85 +/- 3.41 D versus 9.94
      +/- 3.58 D; P = .44), Holladay 1 (9.70 +/- 3.47 D versus 9.80 +/- 3.64 D; P =
      .45), Hoffer Q (9.70 +/- 3.40 D versus 9.85 +/- 3.59 D; P = .37), or Barrett
      Universal II (9.29 +/- 3.52 D versus 9.35 +/- 3.71 D; P = .63) formula.
      CONCLUSIONS: Phakic IOL insertion did not affect IOL power calculation. If
      preoperative data are not available, postoperative values can be used in IOL
      calculation formulas.

PMID- 30274845
TI  - Expression levels of aldose reductase enzyme, vascular endothelial growth factor,
      and intercellular adhesion molecule-1 in the anterior lens capsule of diabetic
      cataract patients.
AB  - PURPOSE: To compare the levels of aldose reductase (ALR) enzyme, intercellular
      adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF) in
      the anterior lens capsule of diabetic versus nondiabetic patients. SETTING:
      Alexandria Main University Hospital, Alexandria, Egypt. DESIGN: Prospective case
      control study. METHODS: The study enrolled patients undergoing cataract
      extraction and divided them into 3 groups: eyes that had proliferative diabetic
      retinopathy (PDR), eyes that had nonproliferative diabetic retinopathy (NPDR),
      and nondiabetic eyes. The anterior lens capsules were obtained by performing
      femtosecond laser-assisted capsulorhexis. Concentrations of ALR, ICAM-1, and VEGF
      in the lens capsule specimens were measured using human enzyme-linked
      immunosorbent assay. RESULTS: This study comprised 200 patients (200 eyes); 51
      eyes had PDR, 49 eyes had NPDR, and 100 eyes were nondiabetic. The mean ALR, ICAM
      1, and VEGF levels in the anterior capsule of diabetic group were 2.84 nanogram
      (ng)/mL +/- 0.51 (SD), 87.73 +/- 22.84 picogram (pg)/mL, and 75.53 +/- 14.95
      pg/mL, respectively; whereas, in the nondiabetic group, they were 1.44 +/- 0.17
      ng/mL, 35.45 +/- 2.8 pg/mL, and 33.55 +/- 5.47 pg/mL, respectively. In comparing
      the concentrations of these mediators, both the PDR and NPDR groups had
      significantly higher levels compared with the nondiabetic eyes (P < .001). In
      addition, eyes with PDR had significantly higher levels of these mediators than
      eyes with NPDR (P < .001). CONCLUSION: The concentrations of ALR, ICAM-1, and
      VEGF in the anterior lens capsule of diabetic patients are significantly higher
      than those of nondiabetics. A significantly higher level of 3 mediators in eyes
      with PDR compared with those with NPDR might allow the use of them as a biomarker
      for severity of diabetic retinopathy.

PMID- 30274846
TI  - Flanged intrascleral intraocular lens fixation with a single needle.

PMID- 30274847
TI  - Modified axial length adjustment formulas in long eyes.

PMID- 30274848
TI  - Efficiency of video-presented information about excimer laser treatment on
      ametropic patients' knowledge and satisfaction with the informed consent process.
AB  - PURPOSE: To evaluate whether the presentation of a video within the informed
      consent consultation affects patient knowledge about refractive excimer laser
      treatment, satisfaction with the informed consent process, anxiety in respect to
      the planned surgery, and the consultation duration. SETTING: Tertiary referral
      center, Lucerne, Switzerland. DESIGN: Single-center, randomized controlled trial.
      METHODS: Consenting eligible patients were randomly assigned to receive either a
      conventional face-to-face consultation (conventional group) or a conventional
      consultation with additional video-assisted information (interventional group).
      Knowledge and satisfaction with the informed consent process and anxiety
      regarding surgery were assessed. Differences between groups were tested with
      Wilcoxon-Mann-Whitney, Chi-square, and Student t tests. RESULTS: The study
      comprised 113 patients (58 in the conventional group and 55 in the interventional
      group). There was no difference in terms of knowledge with 22/25 points
      (interquartile range [IQR], 3) in the conventional group versus 22/25 points
      (IQR, 2) in the interventional group (P = .957), satisfaction with the informed
      consent ("very satisfied": 47/58 versus 45/55; P = .915) and anxiety toward
      surgery with a median 8 (IQR, 4) versus median 9 (IQR, 3; P = .159). In the
      interventional group, however, the total consultation time was significantly
      lower than in the conventional group (-4.96 minutes; 95% CI, -9.50 to -0.43; P =
      .032). CONCLUSION: Compared with a conventional consultation, video-assistance
      slightly reduced the total consultation time while maintaining patient knowledge,
      satisfaction with the informed consent process, and anxiety regarding the surgery
      on equal levels. Video-assistance could increase efficiency of clinical
      management on a double-digit percentage at an equal running cost compared with a
      conventional consultation.

PMID- 30274849
TI  - Cataract surgery in a case of Rosai-Dorfman disease with proptosis.

PMID- 30274850
TI  - Platelet-rich plasma: myth or reality?
AB  - Platelet-rich plasma (PRP) is a preparation for therapeutic purposes that is
      increasingly accepted for various musculoskeletal disorders, due to its
      theoretical potential to repair tissues with poor healing capacity. Several
      randomised clinical trials have investigated the capacity of PRP to repair
      tendons, ligaments, muscles and cartilage, and to date there is level 1a evidence
      to support its use for lateral epicondylitis, osteoarthritis of the knee, plantar
      fasciitis and rotator cuff tendinopathy; and level 1b for patellar tendinopathy
      and osteoarthritis of the hip. Retrospective cohort studies and case series
      describe promising results with PRP for treating other musculoskeletal disorders.
      Since its side effects are fewer than those of the control groups, the treatment
      is considered practically harmless and is being increasingly used. Further
      randomised clinical trials are necessary to establish future indications, and to
      confirm effectiveness and safety.

PMID- 30274851
TI  - Self Limiting Sternal Tumors of Childhood: Two Case Reports.
AB  - Sternal tumours are rare in children. The differential diagnoses include a wide
      spectrum of benign (from bone cyst to osteoblastoma, osteochondroma and fibrous
      displasia) and malignant tumours (Ewing's sarcoma, chondrosarcoma
      rhabdomyosarcoma), inflammatory lesions and infectious processes. The SELSTOC
      (Self Limiting Sternal Tumours of Childhood) are entities of non-specific origin,
      they are self-limiting and characterised by a rapidly growing tumour that
      disappears spontaneously with no history of trauma or active infection. The onset
      of a rapidly growing mass with no preceding trauma is worrying to parents who
      then consult the health professionals. Soft tissue ultrasound enables us to
      characterise these lesions and define their nature in relation to the adjacent
      tissues. Chest x-ray and MRI can also help to characterise these lesions. In this
      paper we present two case reports of children referred to our department for
      characterisation of sternal tumours.

PMID- 30274852
TI  - Compulsory community treatment and ethnicity: Findings from a culturally and
      linguistically diverse area of Queensland.
AB  - OBJECTIVE: To compare the use of community treatment orders (CTOs) and forensic
      orders (FOs) in a culturally and linguistically diverse (CALD) population to that
      in a non-CALD population. METHODS: We analysed the relationship between coming
      from a CALD background and the use of CTOs and FOs on discharge from hospital
      using merged data from the Metro South Addiction and Mental Health Service's
      Transitions of Care (ToC) and Consumer Integrated Mental Health Application
      (CIMHA) databases. RESULTS: Nine hundred and seventy-six individual records were
      included in the data set, of whom eighty-six were from a CALD background (8.8%).
      Three hundred and eleven patients were on compulsory community treatment. Use of
      compulsory community treatment (CTOs and FOs) was similar for those born in
      Australasia, British Isles, North America and Europe but significantly higher for
      those born elsewhere even after adjusting for socio-demographic and clinical
      variables (Adj OR 2.19, 95% CI 1.36-3.52). The use of an interpreter
      significantly increased the likelihood of compulsory community treatment (Adj OR
      2.76, 95% CI 1.20-6.35). Restricting the analyses to CTOs only did not alter
      these results. CONCLUSIONS: Metro South residents from a CALD background outside
      of Europe were over-represented on compulsory community treatment orders. This
      could reflect the difficulties in accessing voluntary services, communication
      barriers, stigma associated with mental illness, discrimination, or issues
      related to accurately diagnosing mental illness cross-culturally. Clinicians need
      to be aware of the complexity of working with people from diverse cultures and
      apply these orders judiciously.

PMID- 30274853
TI  - Phage assembly and the special role of the portal protein.
AB  - Virus infections are ultimately dependent on a successful viral genome delivery
      to the host cell. The bacteriophage family Caudovirales evolved specialized
      machinery that fulfills this function: the portal proteins complex. The complexes
      are arranged as dodecameric rings and are a structural part of capsids
      incorporated at a five-fold vertex. They are involved in crucial aspects of viral
      replication, such as virion assembly, DNA packaging and DNA delivery. This review
      focuses on the organization and the mechanism through which these portal
      complexes achieve viral genome delivery and their similarities to other viral
      portal complexes.

PMID- 30274854
TI  - Distributed point source modeling of the scattering of elastic waves by a
      circular cavity in an anisotropic half-space.
AB  - The Distributed Point Source Method (DPSM) is a modeling technique based on
      superposition of fundamental solutions corresponding to individual pair of source
      and target points. A collection of source points distributed over the boundaries
      and interfaces are responsible for transmission, reflection, and refraction of
      acoustic waves in the solution domain. The strength of the source points may not
      be known a priory. By imposing the prescribed conditions on the boundaries and
      interfaces, a system of equations with the source strengths as the unknowns is
      obtained. After finding the source strengths as the solution to this system of
      equation, the amount of the solution at any target point in the domain is
      obtained by superimposing the effect of all source points on that target point.
      DPSM is an efficient modeling technique for ultrasonic problems since it does not
      require discretization of the whole solution domain but only the boundaries and
      interfaces. The fundamental solution, or the Green's function, between a pair of
      source and target points serves as the building block for DPSM. For an ideal
      fluid or a homogeneous isotropic solid the elastodynamic Green's function is
      available as closed form algebraic expressions. But for an anisotropic solids,
      the set of governing equations are considerably more complex and the
      elastodynamic Green's function needs to be evaluated numerically. In this study,
      an anisotropic half-space containing a flaw in the form of a circular hole is
      considered. The solid half-space is in contact with fluid and a transducer is
      located in fluid facing the solid half-space. Some efforts have been made to
      alleviate the computational intensity of the numerical evaluation of anisotropic
      Green's function for this problem. Firstly, a technique called "windowing" is
      used to exploit the repetitive pattern of relative positions of the source and
      target points in order to considerably reduce the number of Green's function
      evaluations. Secondly, the resolution of the integration for evaluation of the
      anisotropic Green's function is changed based on the distance between the source
      and target points, and a calibration technique based on an equivalent isotropic
      stiffness tensor is suggested. This calibrated multi-resolution integration
      technique is combined with the windowing technique, and the developed DPSM model
      is applied to a numerical example containing a transversely isotropic half-space,
      to show the applicability and effectiveness of DPSM modeling for this class of
      problems. Important applications like non-destructive evaluation of composite
      materials may benefit from such modeling capability.

PMID- 30274855
TI  - Endovascular Treatment of Occlusive Cystic Adventitial Disease.

PMID- 30274856
TI  - Albumin-Bilirubin Score: An Accurate Predictor of Hepatic Decompensation in High
      Risk Patients Undergoing Transarterial Chemoembolization for Hepatocellular
      Carcinoma.
AB  - PURPOSE: To evaluate validity of albumin-bilirubin (ALBI) grade as a predictor of
      acute-on-chronic liver failure (ACLF) after transarterial chemoembolization for
      hepatocellular carcinoma (HCC) in patients with baseline moderate to severe liver
      dysfunction. MATERIALS AND METHODS: In this retrospective study, serum albumin
      and bilirubin levels measured before chemoembolization were used to calculate
      ALBI score in 123 patients treated with 187 high-risk chemoembolizations.
      Procedures were considered high risk if Child-Turcotte-Pugh score before
      chemoembolization was >= 8. ACLF was objectively measured using chronic liver
      failure-sequential organ failure assessment score at 30 and 90 d. The 30-day
      mortality and morbidity from new or worsening ascites and/or hepatic
      encephalopathy (HE) were assessed. Univariate and multivariate analyses were used
      to identify clinical and procedural predictors of ACLF in this high-risk
      population. RESULTS: ACLF occurred after 15 (8%) high-risk chemoembolizations
      within 30 days and an additional 9 (5%) procedures between 30 and 90 days.
      Overall 30-day mortality was 2.7%. New or worsened ascites and/or HE occurred
      after 52 (28%) procedures within 30 days. Significant prognosticators of ACLF at
      90 days revealed by univariate analysis were bilirubin (P = .004), albumin (P =
      .007), and ALBI score (P = .002), with ALBI score remaining statistically
      significant on multivariate regression analysis (OR = 3.99; 95% CI, 1.70-9.40; P
      = .002). CONCLUSIONS: Chemoembolization for HCC can be performed safely in
      patients with moderate to severe liver dysfunction. ALBI score before
      chemoembolization provides objective prognostication for ACLF after
      chemoembolization in this cohort and may be used for risk stratification.

PMID- 30274858
TI  - Viewing the Future of IR through Molecular Histology: An Overview of Imaging Mass
      Spectrometry.

PMID- 30274857
TI  - Adult and Pediatric Antibiotic Prophylaxis during Vascular and IR Procedures: A
      Society of Interventional Radiology Practice Parameter Update Endorsed by the
      Cardiovascular and Interventional Radiological Society of Europe and the Canadian
      Association for Interventional Radiology.

PMID- 30274859
TI  - Generalized Lymphatic Anomaly Associated with Multiple Paraspinal Arteriovenous
      Malformations and Renal Artery Aneurysms.

PMID- 30274860
TI  - The Rise and Decline of Diagnostic Angiography for Renovascular Hypertension: A
      Memoir.

PMID- 30274861
TI  - MR Imaging-Guided Cryoneurolysis of the Sural Nerve.

PMID- 30274862
TI  - Prepare the smoking cessation in severe mental illness: Early diagnosis and
      prevention opportunities.

PMID- 30274863
TI  - Modeling solute reactivity in a phreatic solution conduit penetrating a karst
      aquifer.
AB  - A two-dimensional model for solute migration, transformation, and deposition in a
      phreatic solution conduit penetrating a karst aquifer is presented in which the
      solute is anthropogenic to the natural system. Transformation of a reacting
      solute in a solution conduit has generally been accepted as likely occurring but
      actual physical measurements and mathematical analyses of the suspected process
      have been generally minimally investigated, primarily because of the logistical
      difficulties and complexities associated with solute transport through solution
      conduits. The model demonstrates how a reacting solute might decay or be
      transformed to a product solute some of which then migrates via radial dispersion
      to the conduit wall where it may become adsorbed. Model effects vary for laminar
      flow and turbulent flow in the axial direction. Dispersion in the radial
      direction also exhibits marked differences for both laminar flow and turbulent
      flow. Reaction zones may enhance subsequent reactions due to some overlap
      resulting from the longitudinal dispersion caused by flow in the axial direction.
      Simulations showed that varying the reaction rate coefficient strongly affects
      solute reactions, but that varying deposition coefficients had only minimal
      impacts. The model was applied to a well-known tracer test that used the tracer
      dye, Rhodamine WT, which readily converts to deaminoalkylated Rhodamine WT after
      release, to illustrate how the model may be used to suggest one possible cause,
      in addition to other possible causes, for less than 100 tracer-mass recovery. In
      terms of pollutants in a karst aquifer the model also suggests one possible
      mechanism for pollutant transformation in a solution conduit.

PMID- 30274864
TI  - ?

PMID- 30274866
TI  - Editorial.

PMID- 30274865
TI  - ?

PMID- 30274867
TI  - Potent effect of KISS1-54 DNA vaccine compared with KISS1-10 DNA vaccine in
      inhibiting the fertility of female rats.
AB  - BACKGROUND: Most studies on immunocastration currently focused on male animals.
      However, immunization of male animals does not completely inhibit sexual behavior
      and fertility. This study aimed to compare the immunocastration effect of KISS1
      DNA vaccines encoding different lengths of kisspeptins in female rats for
      effective castration effects on both male and female rats. METHODS: Fifteen
      female rats were randomly divided into three groups. The rats in T1 group or T2
      group was orally given respectively KISS1-54 or KISS1-10 DNA vaccines with fused
      tPA signal peptide, and the control group (Group C) was orally administered with
      empty vector vaccine, at a dose of 5 * 109 CFU/rat at weeks 0, 3 and 6 of the
      study. Blood samples were collected by retroorbital bleeding before primary
      immunization and at weeks 3 and 9 after primary immunization. RESULTS: Both KISS1
      54 and KISS1-10 DNA vaccines induced the body's humoral immune response, and the
      anti-kisspeptin antibody titres in the T1 group were significantly higher than
      that in T2 and C groups (p < 0.05). The rats in T1 group has lower serum
      kisspeptin and estradiol levels than those in T2 and C groups and smaller litter
      size of rats than those in the control group after mating (p < 0.05). No
      significant difference was observed between T2 and C groups. The levels of KISS1
      and GPR54 mRNA in the hypothalamus and ovaries of the T1 group were significantly
      lower than that in control group. However, the levels of KISS1 mRNA in the T2
      group were significantly lower than that in the control group only in ovaries (p
      < 0.05). CONCLUSION: The oral KISS1-54 DNA vaccine with fused tPA signal peptide
      was more effective than that KISS1-10 DNA vaccine in suppressing fertility of
      female rats.

PMID- 30274869
TI  - Shared reality: Construct and mechanisms.
AB  - To provide background for the Special Issue on shared reality, we outline the
      construct of shared reality and underlying mechanisms. Shared reality is the
      experience of having in common with others inner states about the world. Inner
      states include the perceived relevance of something, as well as feelings,
      beliefs, or evaluations of something. The experience of having such inner states
      in common with others fosters the perceived truth of those inner states. Humans
      are profoundly motivated to create shared realities with others, and in so doing
      they fulfill their needs to have valid beliefs about the world and to connect
      with others.

PMID- 30274870
TI  - Editorial: Shared reality.

PMID- 30274868
TI  - Impact of early life exposure to ionizing radiation on influenza vaccine response
      in an elderly Japanese cohort.
AB  - The objective of this study was to evaluate effects of whole body radiation
      exposure early in life on influenza vaccination immune responses much later in
      life. A total of 292 volunteers recruited from the cohort members of ongoing
      Adult Health Study (AHS) of Japanese atomic bomb (A-bomb) survivors completed
      this observational study spanning two influenza seasons (2011-2012 and 2012
      2013). Peripheral blood samples were collected prior to and three weeks after
      vaccination. Serum hemagglutination inhibition (HAI) antibody titers were
      measured as well as concentrations of 25 cytokines and chemokines in culture
      supernatant from peripheral blood mononuclear cells, with and without in vitro
      stimulation with influenza vaccine. We found that influenza vaccination modestly
      enhanced serum HAI titers in this unique cohort of elderly subjects, with
      seroprotection ranging from 18 to 48% for specific antigen/season combinations.
      Twelve percent of subjects were seroprotected against all three vaccine antigens
      post-vaccination. Males were generally more likely to be seroprotected for one or
      more antigens post-vaccination, with no differences in vaccine responses based on
      age at vaccination or radiation exposure in early life. These results show that
      early life exposure to ionizing radiation does not prevent responses of elderly A
      bomb survivors to seasonal influenza vaccine.

PMID- 30274871
TI  - Introduction.

PMID- 30274872
TI  - A Pathway to Publishing an Oncology Nursing Book.
AB  - OBJECTIVES: To describe the process of book publishing, including authoring and
      revising book chapters, and provide resources on book publishing opportunities
      for oncology nurses. DATA SOURCES: Journal articles, book publishers' information
      for authors, online publishing resources, discussions with textbook editors,
      personal experience. CONCLUSION: Few published resources exist to guide nurses as
      they author and/or revise books and book chapters. In addition, book publishing
      presents unique considerations, such as authorship of subsequent editions, and
      new opportunities, such as self-publishing and electronic textbook formats.
      IMPLICATIONS FOR NURSING PRACTICE: Textbooks are enduring repositories of
      comprehensive information used by both students and clinicians. Oncology nurses
      have expert research and clinical expertise that can contribute to this body of
      published nursing knowledge and ultimately improve the care of people with
      cancer.

PMID- 30274874
TI  - Retrospective dosimetric analysis of brain lesions planned in Pinnacle 9.8 via a
      HDMLC linac.
AB  - The University of Toledo Medical Center's Eleanor N. Dana Cancer Center located
      in northwest Ohio currently utilizes the Edge Radiosurgery System (Varian Medical
      Systems Inc., Palo Alto, CA) to deliver stereotactic radiosurgery for the
      treatment of brain lesions. The purpose of this study is to determine the quality
      of conformal arc radiotherapy in treating patients with brain lesions at The
      University of Toledo Medical Center and to provide more data for conformity and
      gradient indices (due to a lack of current data) to hopefully improve national
      standards by allowing centers to compare among each other. Treatment plans were
      assessed using the Pinnacle3 v9.8 Radiation Therapy Planning System (Philips
      Healthcare, Amsterdam, Netherlands). For patients (n = 41) presenting with small
      brain lesions (n = 82) and treated with conformal arc radiotherapy via the Edge
      Radiosurgery System, the RTOG conformity index, Paddick conformity index,
      conformity gradient index, gradient index, and dose gradient index were
      determined for each plan. This study additionally provides data to suggest the
      more accurate method of volume derivation provided by the Pinnacle3 v9.8
      software. Using this method, average values for each of the following indices
      were calculated: RTOG conformity index = 1.36 +/- 0.29; Paddick conformity index
      = 0.72 +/- 0.12; conformity gradient index = 214.67 +/- 12.35; gradient index =
      3.64 +/- 1.09; dose gradient index = -0.11 +/- 0.16. Thus, The University of
      Toledo Medical Center provides favorable conformity of dose to intracranial
      target lesions.

PMID- 30274873
TI  - A Population-Based Study of Intracerebral Hemorrhage Survivors' Outcomes.
AB  - BACKGROUND: We evaluated 3-month neurologic, functional, cognitive, and quality
      of life (QOL) outcomes in intracerebral hemorrhage (ICH) overall, and by sex and
      ethnicity in a population-based study. METHODS: Spontaneous ICH patients were
      identified from the Brain Attack Surveillance in Corpus Christi project (November
      2008 to December 2013). Outcomes included neurologic (National Institutes of
      Health Stroke Scale: range 0-42), functional (activities of daily
      living/instrumental activities of daily living score: range 1-4, higher worse),
      cognitive (Modified Mini-Mental State Examination [3MSE]: range 0-100), and QOL
      (short-form stroke-specific QOL scale: range 0-5, higher better). Ethnic and sex
      differences were assessed with Tobit regression adjusted for age, sex, or
      ethnicity, and presenting Glasgow coma scale. RESULTS: A total of 245 patients
      completed baseline interviews, with 103 (42%) dying prior to follow-up, leaving
      142 eligible for outcome assessment. Three-month follow-up was completed in 100
      (neurologic), 107 (functional), 79 (cognitive), and 83 (QOL) participants. Median
      age was 66 years (interquartile range 58.0-77.0). Cognitive outcomes were worse
      in Mexican Americans (MA) compared to non-Hispanic whites (NHW) after
      multivariable adjustment (MA scoring 13.3 3MSE points lower than NHW [95%
      confidence interval: 5.8, 20.7; P = .0005]). There was no difference by sex or
      ethnicity in neurological, functional, or QOL outcomes, and no sex differences in
      cognitive outcomes. CONCLUSIONS: In this population-based study, worse cognitive
      outcomes were found in MAs compared with NHW. There were no differences between
      neurologic, functional, and QOL outcomes in ICH survivors based on sex or
      ethnicity.

PMID- 30274875
TI  - [...Robotic-assisted latissimus dorsi muscle harvest for immediate breast
      reconstruction].

PMID- 30274876
TI  - Low back pain intensity among childbearing women and associated predictors. A
      cohort study.
AB  - BACKGROUND: Low back pain is a common condition among childbearing women, causing
      physical disability and an increased risk of sick leave and obstetric
      complications. AIMS: To assess the prevalence and intensity of low back pain
      during pregnancy, to describe the physical disability and sick leave in relation
      to the severity of low back pain and to identify predictors of moderate to severe
      low back pain in socio-demographic, health and obstetric characteristics among
      childbearing women. METHODS: A cohort study was undertaken (n=566) during August
      2015 to March 2016. Questionnaires were used to obtain information about low back
      pain intensity, physical disability due to low back pain and sick leave at 20 and
      32weeks of gestation. Of the 654 eligible women, 87% completed the first
      questionnaire. FINDINGS: Three out of four reported any low back pain at 20weeks
      of gestation, and nine out of ten women at 32weeks. Of these women, one in three
      reported moderate to severe pain at 20weeks, increasing to half of the women at
      32weeks. Both sick leave and physical disability increased with increasing low
      back pain scores. Pre-pregnancy low back pain, multiparity and lower level of
      education were all identified as predictors of moderate to severe low back pain.
      CONCLUSIONS: Women with pre-pregnancy low back pain, multiparity and lower level
      of education, represent the group of women with the highest risk of moderate to
      severe low back pain during pregnancy and should be payed special attention.

PMID- 30274877
TI  - Previous breastfeeding experience and its influence on breastfeeding outcomes in
      subsequent births: A systematic review.
AB  - PROBLEM: Despite widely recognized benefits of breastfeeding, the worldwide rate
      of six months exclusive breastfeeding has not up to the WHO recommendation.
      Multiparas are considered more likely to initiate breastfeeding and breastfeed
      much longer. This, however, is not always the case if they have unsuccessful
      previous breastfeeding experience. Therefore, whether and how previous
      breastfeeding experience affect subsequent breastfeeding outcomes need to be
      explored sufficiently. OBJECTIVE: The objective of this review is to summarize
      the evidence of association between previous breastfeeding experience and
      subsequent breastfeeding outcomes. METHODS: A systematic search of Embase, Web of
      Science, PubMed, Cochrane Library and CINAHL databases from inception to March,
      2018 is conducted for cohort studies regarding "previous breastfeeding
      experience" as an influencing factor to subsequent breastfeeding initiation and
      duration. A narrative synthesis is used in this review according to PRISMA and
      study quality is assessed using the Newcastle-Ottawa Scale. FINDINGS: Fifteen
      articles were eligible for this review. Previous breastfeeding experience was
      consistently correlated with subsequent breastfeeding initiation and duration.
      However, previous short breastfeeding duration and unsatisfactory experience
      negatively affected subsequent breastfeeding. CONCLUSIONS: Robust evidence for
      the effect of previous breastfeeding experience on subsequent breastfeeding is
      present. Midwives and breastfeeding/lactation consultants need to provide
      customized interventions for mothers according to detailed previous breastfeeding
      experience in order to improve breastfeeding initiation and breastfeeding
      duration.

PMID- 30274878
TI  - The relationship between maternal weight gain in pregnancy and newborn weight.
AB  - AIM: This study investigated the impacts of different pre-pregnancy body mass
      indexes and gestational weight gain on the risk of delivering a high birth weight
      infant in China. METHODS: A retrospective cohort study was conducted from 2013 to
      2014 in the Maternal and Child Health Care Hospital of Jinan City, Shandong
      Province and 2415 women who had a singleton birth were included in the study. A
      logistic regression model and restricted cubic spline regression were used to
      analyse the association. FINDINGS: The risk of delivering a high birth weight
      infant increases when the mother's pre-pregnancy body mass index exceeds 24kg/m2.
      Compared with women whose pre-pregnancy body mass index was 21kg/m2, the adjusted
      risk of delivering a high birth weight infant doubled when the mother's pre
      pregnancy body mass index was 29kg/m2, and nearly tripled when the mother's pre
      pregnancy body mass index was 31kg/m2. Compared with women who had a gestational
      weight gain of 12.0kg, women having a gestational weight gain of 20.0kg, 22.0kg,
      and 26.0kg had a 1.7-, 2.2-, and 3.5-fold increased risk of delivering a high
      birth weight infant. When the mother experiences a gestational weight gain
      greater than 27kg, the risk of delivering a high birth weight infant is at least
      4-fold greater than that for a mother who has a gestational weight gain of
      12.0kg. CONCLUSIONS: Proposed strategies to raise public awareness of the risks
      to infants posed by high maternal pre-pregnancy body mass index and gestational
      weight gain are required. All clinical recommendations and measures are for all
      pregnant women, not just overweight and obese pregnant women.

PMID- 30274879
TI  - The association between social support and postpartum depression in women: A
      cross sectional study.
AB  - BACKGROUND: Prevalence of postpartum depression is estimated to be about 10-15%
      worldwide. Many risk factors are supposed to play a role leading a new mother to
      maternal postpartum depression which can considerably affect the baby, mother,
      family and also the society. OBJECTIVE: To investigate the prevalence of maternal
      postpartum depression and its association with social support. METHODS: Using a
      cross-sectional study, 200 new mothers who attended three teaching hospitals in
      Tehran, Iran were selected with a convenience sampling. Postpartum depression was
      assessed using the Iranian version of Edinburgh Postpartum Depression Scale and
      women's levels of social support were measured using the Iranian version of
      Social Support Questionnaire. RESULTS: Prevalence of postpartum depression was
      43.5% in new mothers. The mean (+/-Standard Deviation) score of social support
      network was 2.09+/-0.99; which is lower in depressed mothers in comparison to non
      depressed mothers (1.78+/-0.87 vs. 2.33+/-1.00 respectively, P<0.001). A reverse
      significant association was found between social support and postpartum
      depression after adjusting for confounding variables such as past history of
      depression, illness of baby and medication consumption during pregnancy (Odds
      Ratio=0.47, 95% Confidence Interval=0.33-0.67). CONCLUSION: The bigger the social
      network of a mother, the less postpartum depression occurs. It is suggested to
      educate the family about the very important role of social support and improve it
      in every aspect of health care in order to prevent postpartum depression.

PMID- 30274880
TI  - Adaptation of Proximal Femur to Mechanical Loading in Young Adults: Standard Vs
      Localized Regions Evaluated by DXA.
AB  - Regions of the proximal femur with less adaptive protection by mechanical loading
      may be at increased risk of structural failure. Since the size and location of
      these regions diverge from those defined by the dual-energy X-ray absorptiometry
      manufacturers the purpose of this study was to compare areal bone mineral density
      (aBMD) of different regions of the proximal femur considering impact loads from
      physical activity (PA). The participants were 134 young adults divided into 2
      groups according to the impact of PA performed in the last 12 mo: high-impact PA
      and low-impact PA. The aBMD of the proximal femur was assessed by dual-energy X
      ray absorptiometry at the standard femoral neck, intertrochanter, and trochanter,
      and at specific locations of the superolateral femoral neck and intertrochanteric
      region. The bone-specific physical activity questionnaire was used to estimate
      the impact load of PA. Comparisons between groups were adjusted for body height
      and body lean mass. Interaction analysis between sex and PA groups were conducted
      with analysis of variance. Comparisons of aBMD between bone regions were analyzed
      separately for men and women with repeated measures analysis of variance. In the
      high-impact PA group, men benefit more than women at all bone regions, except the
      aBMD at intertrochanteric region. Analyses of repeated measures did not reveal
      any significant interaction effect between bone regions (standard vs specific)
      and PA groups (low vs high-impact). In conclusion, aBMD differences due to
      mechanical loading were more pronounced in men than in women; the magnitude of
      the aBMD differences as a result of different levels of PA was similar between
      standard and localized regions.

PMID- 30274881
TI  - Is recurrent pyogenic cholangitis an independent poor prognostic indicator for
      resectable intrahepatic cholangiocarcinoma?

PMID- 30274882
TI  - Surgical resection of lymph node positive intrahepatic cholangiocarcinoma may not
      improve survival.
AB  - BACKGROUND: Nodal positivity is a predictor of poor survival following resection
      for intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate
      the impact of surgical resection on survival in patients with lymph node (LN)
      positive ICC. METHODS: An augmented version of the Surveillance, Epidemiology,
      and End Results program database was utilized to identify patients with LN
      positive ICC without distant metastases from 2000 to 2014. Patients were
      stratified by treatment: chemotherapy alone or surgical resection with/without
      chemotherapy. Survival was evaluated using Kaplan-Meier and Cox proportional
      hazard models. RESULTS: 169 patients who underwent treatment for LN-positive ICC
      were identified. 88% underwent surgical resection and 12% underwent chemotherapy
      alone. The median survival for patients who underwent surgical resection was not
      different from patients treated with chemotherapy alone (19 months 95% Confidence
      Interval (CI) 17-33 versus 20 months CI 10-27, p = 0.323). A cox-proportional
      hazard ratio model demonstrated that black race was associated with worse
      survival (p < 0.05), while surgical resection was not independently associated
      with survival. CONCLUSION: Surgical resection for patients with LN-positive ICC
      may not improve survival compared to chemotherapy alone. Pathologic LN evaluation
      should be performed prior to surgical resection, to improve patient selection and
      ensure receipt of optimal therapy.

PMID- 30274883
TI  - Management of pregnancy-associated pancreatic cystic tumors: Review of the
      literature and results of a Pancreas Club Inc. Survey.
AB  - BACKGROUND/OBJECTIVES: Management of patients with pregnancy-associated cyst
      pancreatic cystic tumors (PA-PCT) is complicated by lack of large series.
      METHODS: A systematic literature review was conducted to extrapolate data on
      management of PA-PCT, and make a questionnaire on pending issues to be
      administered to the members of the Pancreas Club Inc. RESULTS: The literature
      review demonstrated a total of 35 PA-PCT in 34 women, described exclusively in
      the form of case reports, and permitted the identification of eleven key
      questions to be addressed in the survey. The combined analysis of literature
      review and survery responses provided several information. First, PA-PCT are
      predominantly located in the body-tail of the pancreas, cause non-specific
      symptoms, are of large size (mean size: 11.2 +/- 4.5 cm), and are nearly always
      malignant or premalignant, making timing of surgery, and not indication for
      surgery, the main issue in the management of these tumors. Second, there is a
      risk of PA-PCT rupture during pregnancy. Ruptured PA-PCT had a mean size 13.5 +/-
      4.9 cm, but no prognostic factor could be identified. Survey opinions suggested
      that this occurrence is quite rare, even for large tumors. Third, most
      pregnancies were conducted to term (mean gestational age: 40.5 +/- 0.7 weeks),
      with a vaginal delivery. Fourth, all procedures were carried out through an open
      approach and the spleen was rarely preserved. Survey indicated instead that
      laparoscopy could play a role, and that the spleen should be preserved when
      feasible. CONCLUSIONS: PA-PCT require individualized treatment. The definition of
      a management algorithm requires the implementation of an International Registry.

PMID- 30274884
TI  - Pharmacist perceptions of the New Mexico pharmacist-performed tuberculosis
      testing program.
AB  - OBJECTIVE: This study evaluated pharmacists' perceptions of the New Mexico
      pharmacist-performed tuberculosis skin testing (PPTST) program. METHODS: This
      cross-sectional study was conducted using a telephone survey. New Mexico
      pharmacists who completed the tuberculin skin test (TST) training from March 2011
      to June 2016 were eligible for inclusion. Data collected included demographics,
      years since licensure, pharmacy setting and location, reasons for obtaining
      certification, training time, training quality, self-perceived competency after
      training, whether the participant was performing TSTs, number of tests performed,
      time required to administer or interpret the test, and reasons for not testing.
      RESULTS: We attempted to contact all 209 pharmacists who completed the TST
      training during the evaluation period. Ninety-four of the 99 pharmacists
      contacted consented to participate (overall study response rate of 45%). The
      chain community pharmacy was the most common practice setting of respondents.
      After training completion, greater than 95% agreed or strongly agreed they felt
      confident in administering the TST. The percent of respondents working in New
      Mexico who were actively testing was 50.6%, with 42% of those pharmacists
      providing TSTs in small cities. Eleven pharmacists reported that they were
      performing TSTs in locations where testing would not otherwise have been
      available. An initial TST visit was approximately 6-15 minutes, and follow-up
      visits were typically 5 minutes or less. The most common reason reported for not
      testing was lack of employer support (61%). The strongest association with
      testing was training requirement by employer (odds ratio [OR], 20.4; 95% CI 4.2
      99.2), followed by strong confidence in their ability to perform the TST (OR,
      14.2; 95% CI 2.8-71.2). CONCLUSION: PPTST is positively perceived by New Mexico
      pharmacists and provides testing in non-urban areas where access may be low.
      Survey respondents were confident in their ability to perform the TST and report
      that testing typically takes less than 15 minutes. The main hindrance to
      implementing PPTST was lack of employer support.

PMID- 30274885
TI  - Surgical site infection surveillance for elective primary total hip and knee
      arthroplasty in Winnipeg, Manitoba, Canada.
AB  - BACKGROUND: Surgical site infections (SSIs) increase morbidity and mortality
      after primary hip and knee arthroplasty. We evaluated a surveillance program that
      tracked risk factors associated with infection after primary hip and knee
      arthroplasty in the Winnipeg Regional Health Authority. METHODS: Surveillance
      data from April 2010 to March 2015 were reviewed for all 12,636 primary hip or
      knee arthroplasties, including 1-year follow-up. Procedures were evaluated in
      earlier (April 2010 to December 2012) and later periods (January 2013 to March
      2015). Risk factors for postoperative infection were evaluated. RESULTS: There
      were 154 SSIs in 12,636 operations (1.22%) (earlier, 98 infections in 6,613
      operations [1.48%]; later, 56 infections in 6,023 operations [0.93%]). The
      frequency of primary hip arthroplasty deep infection decreased from earlier to
      later periods; the frequency of primary knee arthroplasty infection was similar
      between the time periods. Independent risk factors associated with increased SSI
      risk included higher body mass index. SSI frequency was inversely associated with
      maintaining immediate postoperative temperature between 36 degrees C and 38
      degrees C and surgery in the later period. CONCLUSIONS: Surveillance was
      effective in decreasing the frequency of deep infection after primary total hip
      arthroplasties but not after knee arthroplasties. Surveillance of orthopedic
      surgery with feedback of SSI rates to the front-line staff may result in
      improvement in surgical outcomes.

PMID- 30274886
TI  - The study of changes in raw meat salting using acoustically activated brine.
AB  - The article for the first time studies the kinetics of the activated brines
      diffusion inside meat based on the research of microstructure and nuclear
      magnetic resonance relaxation. The effect of ultrasound on the increase of
      hydration properties of pork proteins was found positive. The results of the
      experiments prove that spray penetration into not only interfibrillar spaces like
      during jetting but also inside muscle fibers leads to essential changes in meat
      structure, redistribution of brine components and acceleration of biochemical
      processes.

PMID- 30274887
TI  - Synergistic effect of sono-photocatalytic process for the degradation of organic
      pollutants using CuO-TiO2/rGO.
AB  - Combinations of different Advanced Oxidation Processes (AOPs) are being exploited
      for waste water treatment. The usage of ultrasound in photocatalysis finds much
      attention as the combined process offers some advantages over individual
      processes. Herein, we report the ultrasound assisted photocatalytic degradation
      of an organic pollutant (methyl orange as a model dye) in the presence of CuO
      TiO2/rGO photocatalyst which was prepared by a simple wet impregnation method. A
      synergistic effect (3.7-fold) was observed by combining the sonolysis and
      photocatalysis processes. Influence of Cu loading and graphene oxide (GO) dosage
      over the photocatalytic performance of TiO2 was examined in detail. The catalyst
      dosage and initial concentration of MO were optimized based on a series of
      experimental studies. Besides, neutral pH was found to show an optimum efficiency
      for this sono-photocatalytic process.

PMID- 30274888
TI  - Sonochemically recovered silver oxide nanoparticles from the wastewater of photo
      film processing units as an electrode material for supercapacitor and sensing of
      2, 4, 6-trichlorophenol in agricultural soil samples.
AB  - The present work describes the sensing application and supercapacitive behavior
      of silver oxide nanoparticles recovered from wastewater of photo film processing
      units via one-pot green sonochemical recovery process. The recovered silver oxide
      nanoparticles (Ag2O NPs) were characterized by spectral techniques such as FT-IR,
      Raman, UV-Vis and analytical tools such as XRD, FE-SEM, TEM, EDX, XPS and BET. In
      view of Ag2O NPs as electrode material with wide technological applications, the
      recovered Ag2O NPs were examined for their sensing and supercapacitive behavior.
      The developed sensor was explored to detect 2, 4, 6-trichlorophenol, and as
      expected it shows moral parameters which are required of an effective sensor.
      Therefore, it was exploited for the quantification of 2, 4, 6-trichlorophenol in
      soil samples from the agricultural area. Cyclic voltammetric (CV), Galvanostatic
      Charge-Discharge (GCD) and Electrochemical Impedance Spectroscopic (EIS) studies
      on the recovered Ag2O NPs coated Ni foam electrode depicted the pronounced
      capacitive behavior. The GCD studies revealed an enhanced electrochemical
      performance, particularly with the large specific capacitance of 530 F/g at a
      current density of 1 A/g. The cyclic stability of the electrode material was
      identified with 88% retention in specific capacitance even after 5000 GCD cycles.
      These results strongly proved that the recovered Ag2O NPs are potential
      candidates for sensing and supercapacitor applications.

PMID- 30274890
TI  - Cavitation at filler metal/substrate interface during ultrasonic-assisted
      soldering. Part II: Cavitation erosion effect.
AB  - Using pure Sn as filler metal, this study investigated cavitation erosion effects
      during ultrasonic-assisted soldering. The physical process and mechanism of
      cavitation erosion were revealed. Superior erosion effects were observed under
      long ultrasonic times, small channel widths, and high ultrasonic powers.
      Different vibration intensities were obtained inside filler pool. Region I, which
      was located far from the sonotrode, exhibited a stronger vibration intensity and
      better erosion effect than those of the other regions. The erosion incubation
      stage was shorted than 0.5 s at the channel width of 0.2 mm. Complete oxide layer
      removal was obtained at an ultrasonic time of 2 s under this condition. The
      violent cavitation stage was shorter than the erosion incubation stage, and the
      removal of the oxide layer mainly depended on the stable cavitation stage.

PMID- 30274889
TI  - Combined effect of ultrasound treatment and exogenous phytohormones on the
      accumulation of bioactive compounds in broccoli florets.
AB  - Postharvest treatments such as wounding, ultrasound (US) and the exogenous
      application of ethylene (ET) and methyl jasmonate (MJ) have been studied as an
      effective tool to improve the content of secondary metabolites in fresh produce.
      The present study evaluated the immediate and late response (storage for 72 h at
      15  degrees C) to US treatment (20 min, frequency 24 kHz, amplitude 100 MUm)
      alone and combined with exogenous MJ (250 ppm) and/or ET (1000 ppm) on
      glucosinolates, isothiocyanates, phenolic compounds and ascorbic acid content in
      broccoli florets. US treatment increased the extractability of glucosinolates
      [glucoraphanin (795%), 4-hydroxy glucobrassicin (153%), glucobrassicin (78.6%)]
      and phenolics [1-sinapoyl-2-feruloylgentiobiose (57.23%)] as compared with the
      control (CT). The combined application of MJ and US in broccoli florets, induced
      a synergistic effect on the accumulation of 4-hydroxy glucobrassicin (187.1%),
      glucoerucin (111.92%), gluconasturtiin (755.9%), neoglucobrassicin (232.8%), 3-O
      caffeoylquinic acid (73.4%), 1-sinapoyl-2-ferulolylgentiobiose (56.0%), and 1,2,2
      trisinapoylgentiobiose (136.7%) at 72 h of storage. Interestingly, when the three
      stressors were applied together the synergistic effect of US + MJ observed on the
      accumulation of glucosinolates and phenolics was repressed. In general, the
      ascorbic acid content was not affected by US treatment and decreased in most
      samples during storage. However, when MJ + ET were applied, the content of total
      ascorbic acid was significantly reduced in CT + MJ + ET and US + MJ + ET samples
      after 72 h of storage by 53.4% and 86.6%, respectively, as compared with CT 0 h
      samples. Based on the results herein obtained, the application of US can be an
      effective tool to enhance the extractability of certain glucocosinolate and
      phenolic compounds in broccoli. Moreover, due to the synergistic effect observed
      on the accumulation of bioactive compounds, the combined application of US and MJ
      could be a practical approach to yield higher levels of glucosinolates and
      phenolic compounds in broccoli during storage.

PMID- 30274891
TI  - Investigations on sonofragmentation of hydroxyapatite crystals as a function of
      strontium incorporation.
AB  - Hydroxyapatite (Ca10(PO4)6(OH)2, HA) is chemically similar to the mineral
      component of bones and hard tissues in mammals. Various cations can substitute
      calcium in the crystal structure of hydroxyapatite. Among them strontium triggers
      interest, because strontium incorporated hydroxyapatite increases the number of
      bone forming sites in addition to having good biocompatibility. In the present
      investigation strontium substituted hydroxyapatite (SHA) in the compositions
      range 0, 10, 20, 50 and 100 mol% have been synthesized by precipitation method
      and subjected to ultrasonic treatment for different time intervals to gain
      insight on the role of ultrasound in modifying the morphology of SHA. This study
      reveals that the aspect ratio of SHA varied with the duration of ultrasonication.
      SHA samples subjected to 5 min ultrasound experienced an increase in aspect
      ratio. Further increase of ultrasonication time tends to decrease the aspect
      ratio invariably for all SHA samples indicating particle fragmentation. The
      extent of sonofragmentation as a function of percentage incorporation of
      strontium in HA lattice has been studied as a part of the present investigation.
      This study indicated that strain in the HA lattice has correlation with strontium
      incorporation, leading to varied extent of sonofragmentation. Also, the
      investigation suggested that 100% substitution of calcium sites by strontium
      leads to a relatively lesser strain and hence poor fragmentation. To the best of
      our knowledge the report on sonofragmentation of HA crystallites as a function of
      strontium incorporation is first of its kind in the literature.

PMID- 30274892
TI  - Ultrasonic assisted synthesis of magnetic Ni-Ag bimetallic nanoparticles
      supported on reduced graphene oxide for sonochemical simultaneous removal of
      sunset yellow and tartrazine dyes by response surface optimization: Application
      of derivative spectrophotometry.
AB  - The magnetic Ni-Ag bimetallic nanoparticles supported on reduced graphene oxide
      (Ni-Ag NPs/rGO) was synthesized and characterized by transmission electron
      microscopy (TEM), energy dispersive X-ray analysis (EDX), field emission scanning
      electron microscopy (FE-SEM) and vibrating sample magnetometer (VSM).
      Subsequently, this magnetic hybrid material as a novel adsorbent was applied for
      the sonochemical simultaneous removal of sunset yellow and tartrazine dyes in
      combination with first-order derivative spectrophotometric method to resolve the
      overlap between the spectra of these dyes. With magnetic properties, the
      adsorbent could easily be collected from aqueous solution using an external
      magnetic field. The parameters including initial concentration of each dye,
      adsorbent dosage and sonication time were studied by Box-Behnken design (BBD) and
      response surface methodology (RSM), while pH was studied by one-at-a-time
      approach. According to Box-Behnken design based on desirability function (DF),
      the best experimental conditions was set as initial sunset yellow concentration
      10 mgL-1, initial tartrazine concentration 8.5 mgL-1, adsorbent dosage 0.045 g
      and sonication time of 15 min. The equilibrium data was fitted to different
      isotherm models and the results revealed the suitability of the Langmuir model.
      The maximum sorption capacity calculated from the Langmuir model was 28.57 and
      26.31 mg g-1 for sunset yellow and tartrazine, respectively. Kinetic data
      revealed that the adsorption process followed a pseudo-second-order model. The
      reusability of the magnetite nanoparticles revealed about 8% decrease in the
      removal efficiency within four consecutive runs.

PMID- 30274893
TI  - Risk factors for and molecular characteristics of methicillin-resistant
      Staphylococcus aureus nasal colonization among healthy children in southern
      Taiwan, 2005-2010.
AB  - BACKGROUND/PURPOSE: Nasal colonization of Staphylococcus aureus is a well-defined
      risk factor for subsequent infection. This study investigated the prevalence of
      methicillin-resistant S. aureus (MRSA) in southern Taiwan and aimed to identify
      the host factors for S. aureus colonization and the virulence factor of Panton
      Valentine Leukocidin (PVL) genes. METHODS: In a hospital-based study in Kaohsiung
      from Oct. 2005 to Dec. 2010, we performed nasal swab in the healthy children aged
      2-60 months. We examined the relationship between the demographic characteristics
      and S. aureus nasal colonization. MRSA isolates were further analyzed for
      antimicrobial susceptibility and molecular characteristics. RESULTS: Among 3020
      healthy children, 840 (27.8%) children had S. aureus nasal colonization. Of 840
      isolates, 246 (29.3%) isolates were MRSA. MRSA colonization was significantly
      associated with age 2-6 months, day care attendance, and influenza vaccination.
      Breastfeeding was a protective factor against MRSA colonization. Most MRSA
      isolates were susceptible to trimethoprim-sulfamethoxazole and doxycycline.
      Ninety-four percent of MRSA isolates carried either type IV staphylococcal
      cassette chromosome mec (SCCmec) or SCCmec VT and 87% belonged to the local
      community strains, namely clonal complex 59/SCCmec IV or VT. MRSA isolates with
      PVL-negative was associated with children with passive smoking. CONCLUSIONS:
      Between 2005 and 2010, 27.8% and 8.14% of healthy children in southern Taiwan had
      nasal carriage of S. aureus and MRSA, respectively. Most MRSA isolates were local
      community strains. Several demographic factors associated with nasal MRSA
      colonization were identified.

PMID- 30274894
TI  - Comparisons of clinical features and outcomes between Elizabethkingia
      meningoseptica and other glucose non-fermenting Gram-negative bacilli bacteremia
      in adult ICU patients.
AB  - BACKGROUND: Clinical information of Elizabethkingia meningoseptica (EM)
      bacteremia in intensive care unit (ICU) patients is limited and the impact on
      outcomes uncertain. The aim of this study was to investigate the clinical
      features and impact of EM bacteremia compared to other glucose non-fermenting
      Gram-negative bacilli (GNF-GNB) bacteremia in ICU patients. METHODS: This
      retrospective cohort study enrolled 70 patients who developed GNF-GNB bacteremia
      after ICU admission, including 19 cases of EM bacteremia (19/70, 27.1%). The main
      outcome measure was in-hospital mortality. RESULTS: The patients with EM
      bacteremia had a lower rate of appropriate antibiotic therapy (15.8% vs. 62.7%, p
      < 0.001) and a longer time to appropriate antibiotic therapy (76.8 +/- 46.4 vs.
      35.1 +/- 38.7 h, p < 0.001), but with a less severity in acute physiology and
      chronic health evaluation (APACHE) II score and shock status (p < 0.05) at the
      onset of bacteremia, compared to those with non-EM bacteremia. The in-hospital
      mortality between those with EM bacteremia and non-EM bacteremia was similar
      (63.2% vs. 51.0%, p = 0.363). However, primary bacteremia was more frequently
      noted in EM compared with non-EM group (57.9% vs. 25.5%, p = 0.011), and odds
      ratio 4.294 (95% confidence interval 1.292-14.277, p = 0.017) in multivariate
      regression analysis. CONCLUSION: Among the patients with GNF-GNB bacteremia, the
      numbers of the cases with primary bacteremia and inappropriate therapy were
      significantly more in EM group than those in non-EM group.

PMID- 30274895
TI  - Current Status of Antithrombotic Therapy in Patients With Breast Cancer and
      Atrial Fibrillation.

PMID- 30274896
TI  - Circulation of single serotype of Dengue Virus (DENV-3) in New Delhi, India
      during 2016: A change in the epidemiological trend.
AB  - BACKGROUND: Dengue is a rapidly emerging arthropod borne viral infection
      affecting tropical and sub-tropical regions of the world. Dengue is an acute
      febrile illness but sometimes causes more fatal complications like dengue
      haemorrhagic fever (DHF) and dengue shock syndrome (DSS). Delhi, the capital of
      India has become hyper endemic for dengue virus because all the four serotypes
      are circulating here. METHODS: The present study describes the identification of
      dengue virus from clinical samples collected from the suspected dengue patients
      from New Delhi, India during 2016. The CprM region of Dengue virus genome was
      analyzed for phylogenetic, selection pressure and Shannon entropy analyses.
      RESULTS: The present study reports circulation of a single serotype (DENV-3) in
      New Delhi, during 2016. The phylogenetic analysis revealed that Indian
      subcontinent (genotype III) of DENV-3 was circulating in Delhi during this
      period. Neutral selection pressure in the analyzed region revealed relatively
      conserved nature of this part of the Dengue virus genome. Amino acid at 31 was
      positively selected and had high entropy value suggesting probability of
      variation at this position. CONCLUSIONS: The changing trend in circulation of
      dengue virus serotypes necessitates the continuous epidemiological surveillance
      for the dengue outbreaks in this region.

PMID- 30274897
TI  - Criteria for spiritual support in critical care.

PMID- 30274898
TI  - High-protein diets for weight management: Interactions with the intestinal
      microbiota and consequences for gut health. A position paper by the my new gut
      study group.
AB  - BACKGROUND & AIMS: This review examines to what extent high-protein diets (HPD),
      which may favor body weight loss and improve metabolic outcomes in overweight and
      obese individuals, may also impact the gut environment, shaping the microbiota
      and the host-microbe (co)metabolic pathways and products, possibly affecting
      large intestine mucosa homeostasis. METHODS: PubMed-referenced publications were
      analyzed with an emphasis on dietary intervention studies involving human
      volunteers in order to clarify the beneficial vs. deleterious effects of HPD in
      terms of both metabolic and gut-related health parameters; taking into account
      the interactions with the gut microbiota. RESULTS: HPD generally decrease body
      weight and improve blood metabolic parameters, but also modify the fecal and
      urinary contents in various bacterial metabolites and co-metabolites. The effects
      of HPD on the intestinal microbiota composition appear rather heterogeneous
      depending on the type of dietary intervention. Recently, HPD consumption was
      shown to modify the expression of genes playing key roles in homeostatic
      processes in the rectal mucosa, without evidence of intestinal inflammation.
      Importantly, the effects of HPD on the gut were dependent on the protein source
      (i.e. from plant or animal sources), a result which should be considered for
      further investigations. CONCLUSION: Although HPD appear to be efficient for
      weight loss, the effects of HPD on microbiota-derived metabolites and gene
      expression in the gut raise new questions on the impact of HPD on the large
      intestine mucosa homeostasis leading the authors to recommend some caution
      regarding the utilization of HPD, notably in a recurrent and/or long-term ways.

PMID- 30274899
TI  - Proposed standard model and consistent terminology for monitoring and outcome
      evaluation in different dietetic care settings: Results from the EU-sponsored
      IMPECD project.
AB  - BACKGROUND & AIMS: Dietetic interventions contribute to certain health objectives
      and other outcomes, but are mostly part of a multimodal and multidisciplinary
      approach what makes evaluating the actual effects of dietitians' involvement
      rather complex. Although monitoring and outcome evaluation (M&OE) can provide
      routine data to prove the effectiveness of dietetic interventions, this has not
      been established yet in different dietetic settings. METHODS: A comprehensive
      framework for M&OE in dietetics was developed by dietetic experts from five
      European higher education institutes for dietetics in the course of the EU
      sponsored project "Improvement of Education and Competences in Dietetics
      (IMPECD)". RESULTS: Firstly, clear definitions on M&OE are proposed to facilitate
      the use of consistent terminology, with a specific emphasis on the term "impact"
      covering macro-level outcomes such as cost-effectiveness. Secondly, the Dietetic
      Care Process (DCP) was merged into a logic model to demonstrate the position of
      M&OE in relation to intervention planning and implementation, in both group and
      individual settings. Thirdly, selecting the appropriate indicators is
      indispensable to monitor and evaluate outcomes, and requires a high level of
      dietitians' critical reasoning. A categorized overview of indicators is provided
      to support this process. Lastly, the consortium developed a checklist to give
      dietitians a handle on what elements could be included in their M&OE plan and
      trigger them to perform M&OE in practice. CONCLUSIONS: Innovative M&OE models may
      help dietitians to demonstrate their effectiveness in improving clinical outcomes
      and justify their role in health care.

PMID- 30274900
TI  - Association between fibre intake and indoxyl sulphate/P-cresyl sulphate in
      patients with chronic kidney disease: Meta-analysis and systematic review of
      experimental studies.
AB  - BACKGROUND AND OBJECTIVE: Indoxyl sulphate (IS) and p-cresyl sulphate (PCS),
      which are difficult to excrete adequately out of the body, are closely related to
      the progression of chronic kidney disease (CKD) and various deuteropathy. Better
      than peritoneal dialysis (PD) and haemodialysis (HD), dietary fibre has been
      considered to reduce IS and PCS levels. In view of the absence of formal
      recommendations on fibre intake in CKD nutritional guidelines, we conducted this
      meta-analysis to assess the effects of dietary fibre on IS and PCS for CKD
      patients. METHODS: The effects were pooled and expressed in terms of weighted
      mean difference (WMD) with 95% confidence interval (95% CI). Q test and I2
      statistics were used to assess the heterogeneity. RESULTS: A total of 12 relevant
      estimates from 7 reports, including 203 CKD patients, showed that dietary fibre
      significantly reduced their PCS level (WMD = -16.160, 95% CI: -23.824, -8.495).
      CONCLUSIONS: The meta-analysis produced a strong corroboration that dietary fibre
      intake does have a good therapeutic effect on patients with CKD. The conclusions
      need to be validated by randomised controlled experiments (RCT) with better
      design, larger samples, longer course of treatment and higher quality.

PMID- 30274901
TI  - Patient experiences of initial trauma care.
AB  - BACKGROUND: Correct initial treatment of trauma patients reduces mortality and
      morbidity. However, the initial examination may be perceived as traumatic because
      of the stressful situation, the unfamiliar setting and the shock of being
      seriously injured. To date, little is known about patient's experiences of
      initial trauma management. The aim of this study was to explore trauma patients'
      experiences of being exposed to initial full trauma team assessment at a Level 1
      trauma centre. METHODS: Interviews with 16 patients who had been exposed to
      initial trauma care were conducted at a Level 1 trauma centre, at a Swedish
      University Hospital. The interviews were transcribed verbatim and analysed with
      qualitative content analysis. RESULTS: Patients' experiences of initial trauma
      care can be summarized as: feeling safe in a frightening situation. The trauma
      team members were mostly perceived as professional, well-organised, and
      efficient. Yet, the patients described an emotional response to the trauma,
      physical discomfort during the examination, and feeling prioritised or being
      ignored in the encounter with the trauma team members. CONCLUSION: The initial
      trauma care may be improved if the trauma team members keep the patient's
      physical and emotional wellbeing in focus and maintain an informative dialogue
      with the patient during the whole process.

PMID- 30274902
TI  - Management of immune thrombocytopenia in elderly patients.
AB  - Despite the improvement in understanding its pathogenesis and the introduction of
      novel treatment options, the management of primary immune thrombocytopenia (ITP)
      still remains challenging. Considering its increased incidence with aging and
      prolonged life-expectancy, ITP is often diagnosed in elderly patients, a subset
      that deserves some special precautions. Ensure the diagnosis is a crucial step,
      and carefully attention must be given in excluding other causes of
      thrombocytopenia, especially among older people that frequently suffer from many
      comorbidities. When it comes to treatment decision, it is worth keeping into
      account that the elderly have an increased risk of bleeding, thrombosis and
      infections, that they often require many concomitant therapies, including
      antiplatelet or anticoagulant agents, and that treatment-related toxicities are
      often increased and sometimes more dangerous that the disease itself. There are
      not dedicated guidelines, and only few specific studies. Steroids with or without
      IVIG remain the first-line treatment. Splenectomy is less effective than in
      youngers and burdened by an increased thrombotic and infectious risk. Rituximab
      is a good option in non-immunocompromised patients, but long-term remissions are
      few. Eltrombopag and romiplostim have a good safety and efficacy profile, and
      have become a prominent drug in this subset, even if they are associated with a
      possible increased risk of thrombosis, and long-term toxicity is unknown. Other
      drugs, such as dapsone and danazol, have a well-known efficacy and safety
      profile, and still represent a valid option among elderly patients.

PMID- 30274903
TI  - Starting anticoagulation with vitamin k antagonists alone or with concomitant low
      molecular weight heparin for non-valvular atrial fibrillation.

PMID- 30274904
TI  - Health economic aspects of late preterm and early term birth.
AB  - Despite an increasing body of knowledge on the adverse clinical sequelae
      associated with late preterm birth and early term birth, little is known about
      their economic consequences or the cost-effectiveness of interventions aimed at
      their prevention or alleviation of their effects. This review assesses the health
      economic evidence surrounding late preterm and early term birth. Evidence is
      gathered on hospital resource use associated with late preterm and early term
      birth, economic costs associated with late preterm and early term birth, and
      economic evaluations of prevention and treatment strategies. The article
      highlights the limited perspective and time horizon of most studies of economic
      costs in this area; the limited evidence surrounding health economic aspects of
      early term birth; the gaps in current knowledge; and it discusses directions for
      future research in this area, including the need for validated tools for
      measuring preference-based health-related quality-of-life outcomes in infants
      that will aid cost-effectiveness-based decision-making.

PMID- 30274905
TI  - High fatigue frequency in narcolepsy type 1 and type 2 in a Brazilian Sleep
      Center.

PMID- 30274906
TI  - Ideal Cardiovascular Health and Incident Cardiovascular Disease Among Adults: A
      Systematic Review and Meta-analysis.
AB  - OBJECTIVE: To investigate the association between ideal cardiovascular health
      (CVH) metrics and incident cardiovascular disease (CVD) by conducting a
      systematic review and meta-analysis of prospective cohort studies. METHODS: The
      MEDLINE, EMBASE, and CINAHL databases were searched from January 1, 2010, through
      July 31, 2017, for studies that met the following criteria: (1) prospective
      studies conducted in adults, (2) with outcome data on CVD incidence and (3) a
      measure of ideal CVH metrics. RESULTS: Twelve studies (210,443 adults) were
      included in this analysis. Compared with adults who met 0 to 2 of the ideal CVH
      metrics (high-risk individuals), a significantly lower hazard for CVD incidence
      was observed in those who had 3 to 4 points for the ideal CVH metrics (hazard
      ratio [HR]=0.53; 95% CI, 0.47-0.59) and 5 to 7 points (HR=0.28; 95% CI, 0.23
      0.33). Weaker associations were observed in studies with older individuals,
      suggesting that there is a positive relationship between age and HR. CONCLUSION:
      Although meeting 5 to 7 metrics is associated with the lowest hazard for CVD
      incidence, meeting 3 to 4 metrics still offers an important protective effect for
      CVD. Therefore, a realistic goal in the general population in the short term
      could be to promote at least an intermediate ideal CVH profile (3 to 4 metrics).

PMID- 30274907
TI  - Effect of Cognitive Status on the Receipt of Procedures Requiring Anesthesia and
      Critical Care Admissions in Older Adults.
AB  - OBJECTIVE: To investigate whether older adults with mild cognitive impairment
      (MCI) or dementia have higher rates of procedures requiring general anesthesia or
      intensive care unit (ICU) admissions compared with cognitively normal (CN)
      patients. PATIENTS AND METHODS: A population-based cohort, 70 to 89 years old at
      enrollment, underwent clinical and longitudinal neurocognitive testing to
      identify those with MCI and dementia. We analyzed the effects of cognitive status
      (CN, MCI, or dementia) at entry into the study from October 1, 2004, through
      December 31, 2014, on the risk of receiving procedures requiring surgical
      anesthesia and ICU admission. RESULTS: Of 2436 participants, 1977 (81%) were CN,
      387 (16%) had MCI, and 72 (3%) had dementia. Cognitively impaired individuals
      were sicker. Compared with CN individuals, the likelihood of receiving a
      procedure requiring anesthesia was similar in participants with MCI (adjusted
      hazard ratio [aHR]=0.98; P=.78). Participants with dementia were less likely to
      receive these procedures (aHR=0.50; P=.02). Compared with CN participants, the
      likelihood of ICU admission for any indication was increased for those with MCI
      (aHR=1.24; P=.03) and dementia (aHR=1.59; P=.04). Admissions to the ICU after
      procedures were not different in patients with either MCI or dementia (aHR=0.96;
      P=.83 and aHR=1.01; P=.98, respectively). CONCLUSION: Patients with MCI or
      dementia are not more likely to undergo surgery, and neither are they more likely
      to require ICU admission after procedures. An increased rate of nonsurgical ICU
      admissions requires vigilance to prevent deterioration of nonsurgical diseases
      that may lead to ICU admissions.

PMID- 30274908
TI  - Concordance and Discordance of Sexual Identity, Sexual Experience, and Current
      Sexual Behavior in 45-Year-Old Men: Results From the German Male Sex-Study.
AB  - INTRODUCTION: Discordance of various aspects of sexual orientation has been
      mostly studied in young adults or in small samples of heterosexual men. Studies
      focusing on concordance and discordance of aspects of sexual orientation in
      representative samples of middle-aged men including homosexual men are scarce.
      AIM: To investigate concordant and discordant sexual behavior in 45-year-old
      German men with a special focus on homosexual identified men. METHODS: Data for
      this cross-sectional study were collected within the German Male Sex-Study.
      Participants were 45-year-old Caucasian males from the general population. Men
      self-reported on sexual identity, sexual experience, and current sexual behavior.
      Associations between sexual identity, experience, and behavior were analyzed
      using the chi-square test. MAIN OUTCOME MEASURE: Associations of sexual identity
      with sexual experience and behavior in a community-based sample of men, and
      discordance of sexual identity and behavior especially in the subgroup of
      homosexual men. RESULTS: 12,354 men were included in the study. 95.1% (n =
      11.749) self-identified as heterosexual, 3.8% (n = 471) as homosexual, and 1.1%
      (n = 134) as bisexual. Sexual identity was significantly associated with sexual
      experience and behavior. 85.5% of all men had recently been sexually active, but
      prevalence of sexual practices varied. In hetero- and bisexuals, vaginal
      intercourse was the most common sexual practice, whereas oral sex was the most
      common in homosexuals. A discordance of sexual identity was especially found in
      homosexual men: 5.5% of homosexuals only had sexual experiences with women, and
      10.3% of homosexuals recently had vaginal intercourse. In this latter subgroup,
      only one-quarter ever had sexual experience with a man, and three-quarters had
      only engaged in sexual activity with a woman. CONCLUSION: Sexual identity is
      associated with differences in sexual experience and behavior in German middle
      aged men. A considerable proportion of homosexual identified men live a
      heterosexual life. Goethe VE, Angerer H, Dinkel A, et al. Concordance and
      Discordance of Sexual Identity, Sexual Experience, and Current Sexual Behavior in
      45-Year-Old-Men: Results From the German Male Sex-Study. Sex Med 201;6:282-290.

PMID- 30274909
TI  - Verteporfin as a Medical Treatment in Peyronie's Disease.
AB  - INTRODUCTION: In Europe and the United States, verteporfin (Visudyne; VP) is
      registered and used in treating macular degeneration. Research showed that VP
      decreased expression of fibrotic genes in fibroblasts collected from nodules of
      patients suffering from Dupuytren's disease, plausibly by de-activating
      transcription in the Yes Activated Protein (YAP) pathway. AIM: To analyze the
      effect of VP on myofibroblasts cultured from Peyronie's disease (PD) plaques.
      METHODS: At surgery for PD we took biopsies from the plaques of 5 patients. By
      immunostaining, the presence of the pathologic myofibroblasts was determined.
      After culturing cells, VP was dispensed in starvation medium for 24 and 48 hours
      and messenger(m)RNA levels of COL1A1, ACTA2, COL5A1, EDA-FN, LOXL2, CCN2,
      SERPINH1, PLOD2, and YAP were quantified and compared with controls with real
      time polymerase chain reaction. MAIN OUTCOME MEASURE: mRNA-levels of COL1A1,
      ACTA2, COL5A1, EDA-FN, LOXL2, CCN2, SERPINH1, PLOD2, and YAP. RESULTS: The
      pathologic phenotype of cells isolated from PD plaques was confirmed with
      baseline immunofluorescent stainings that showed considerable levels of alpha
      smooth muscle actin, being a marker for the presence of myofibroblasts. The mRNA
      ratios of all the genes related to fibrosis (COL1A1, etc.) except YAP decreased
      significantly after treatment with VP within 24 and 48 hours. These results
      suggest inhibition of fibrosis in the YAP cascade, downstream of YAP. CONCLUSION:
      In our opinion, urologists must move the focus to disease before deformity, and
      the search for new oral or intralesional agents, well-tolerated and effective in
      both the acute and chronic phase of PD must continue. VP blocked the expression
      of genes related to fibrosis in the YAP cascade in myofibroblasts derived from PD
      plaque. Mohede DCJ, de Jong IJ, Bank RA, et al. Verteporfin as a medical
      treatment in Peyronie's disease. Sex Med 2018;6:302-308.

PMID- 30274910
TI  - Simvastatin ameliorates total liver ischemia/reperfusion injury via KLF2-mediated
      mechanism in rats.
AB  - OBJECTIVE: The total hepatic ischemia/reperfusion injury (IRI) involves the fact
      that both liver and gut are subjected to warm ischemia, which is a complex
      unavoidable process encountered during liver transplantation and a serious threat
      to graft outcome. The ways to improve hepatic IRI are currently limited. The aim
      of the present study was to explore the protective effect of simvastatin on total
      hepatic IRI and examine the underlying mechanisms. METHODS: Male Sprague Dawley
      rats were subjected to total (100%) hepatic warm ischemia to induce hepatic IRI.
      Thirty-six male rats (250-300 g) were randomly divided into three groups: sham,
      IRI control and simvastatin (1 mg/kg) pretreatment 0.5 h before surgery. Serum
      samples and liver tissues were collected after reperfusion at 6 and 24 h for
      further studies. RESULTS: Simvastatin pretreatment significantly decreased the
      values of the transaminases alanine aminotransferase and aspartate
      aminotransferase and improved histological alterations according to improved
      Suzuki's Score (P < 0.05). Moreover, simvastatin upregulated the expression of
      Kruppel-like factor 2 (KLF2), phosphorylated endothelial nitric oxide synthase
      and thrombomodulin (P < 0.05). Furthermore, simvastatin pretreatment affected
      superoxide dismutase and malondialdehyde activities (P < 0.05) to reduce
      oxidative stress, and inhibited levels of high-mobility group box-1, CD68, toll
      like receptor 4, tumor necrosis factor alpha, interleukin-1beta and interleukin-6
      (P < 0.05) to suppress inflammatory response. CONCLUSION: Simvastatin
      pretreatment ameliorates total hepatic IRI via a KLF2-mediated protective
      mechanism. Simvastatin may be used as a potential prophylactic treatment strategy
      for clinical trials against hepatic IRI.

PMID- 30274912
TI  - Effect of Fat Grafting on Postoperative Intraabdominal Adhesions on a Rat Model.
AB  - BACKGROUND: We aimed to evaluate the effect of fat grafting on postoperative
      intraabdominal adhesions by promoting mesothelial healing on a rat model.
      METHODS: Thirty Wistar albino rats were grouped as control and fat grafted group.
      They all underwent laparotomy, anterior cecal wall abrasion and peritoneal
      injury. On postoperative day 14, all surviving rats were sacrificed and
      adhesions, fibrosis and inflammation were graded using quantitative scoring
      systems. RESULTS: Fat grafting significantly reduced adhesion formation compared
      to the control group (p <0.002), less fibrosis (p <0.025) and less inflammation
      (p <0.024). CONCLUSIONS: Autologous intraperitoneal fat grafting promotes
      mesothelial healing in serosal and peritoneal injury rat model. The present study
      underlines the benefits of the pluripotent stem cell reservoir fat tissue and
      points to a new area of use. Results are promising for reducing adhesions,
      adhesion related morbidities and cost burden via a simple, cheap and applicable
      method; autologous fat grafting.

PMID- 30274911
TI  - Association of glycated hemoglobin with the risk of advanced fibrosis in non
      alcoholic fatty liver disease patients without diabetes.
AB  - BACKGROUND: Association of diabetes with non-alcoholic steatohepatitis has been
      well documented. However, it remains unclear whether there is an association
      between levels of glycated hemoglobin (HbA1c) with severity of non-alcoholic
      fatty liver disease (NAFLD). This study was aimed to explore the relationship
      between levels of HbA1c and the risk of advanced fibrosis in patients with NAFLD.
      METHODS: A cross-sectional study was performed on 4826 apparently healthy
      Chinese, who underwent a health check between January 2015 and December 2016.
      NAFLD was defined as hepatic steatosis on ultrasonography in the absence of
      excessive alcohol use or other identifiable causes. The risk of advanced fibrosis
      was assessed by NAFLD fibrosis Score. RESULTS: Among 4826 individuals studied,
      1630 were diagnosed with NAFLD. In a multivariable-adjusted model, high HbA1c
      levels were associated independently with increased prevalence of NAFLD. The
      adjusted odds ratio [95% confidence interval (95% CI)] for NAFLD, when compared
      with the highest HbA1c quartile and the lowest HbA1c quartile, was 2.72 (2.07
      3.58; P for trend < 0.001). A strong association was also observed between HbA1c
      level and the risk of fibrosis in patients with NAFLD in multivariable analyses,
      with the extreme-quartile odds ratio of 2.69 (95% CI: 1.60-4.53; P for trend <
      0.001). This association remained significant even in subjects without diabetes.
      CONCLUSIONS: We concluded that high HbA1c level was associated strongly and
      independently with increased risk of advanced fibrosis in NAFLD patients without
      diabetes.

PMID- 30274913
TI  - Association Between miR-149 Gene rs2292832 Polymorphism and Risk of Gastric
      Cancer.
AB  - BACKGROUND AND AIMS: Accumulating evidence suggested that microRNA (miRNA) genes
      take part in different processes associated with gastric cancer (GC). The single
      nucleotide polymorphisms (SNPs) located on miRNA sequences may affect the
      interaction with their target mRNAs and consequently the genetic susceptibility
      to GC. MATERIALS/METHODS: A hospital-based case-control study with 320 cases and
      354 controls was conducted to investigate the association between miR-149 gene
      rs2292832 polymorphism and GC susceptibility in a Chinese Han population.
      RESULTS: TT genotype or T allele carriers of miR-149 gene rs2292832 polymorphism
      increased the risk of GC. Furthermore, a meta-analysis together with this study
      between this SNP and GC risk was performed. In the allele association study, meta
      analysis between this polymorphism and GC risk showed that T or C allele was not
      associated with the risk of GC, but TC genotype carriers of miR-149 gene
      rs2292832 polymorphism were associated with decreased risk of GC (TC vs. CC,
      heterozygote model: OR and 95% CI, 0.80 [0.67,0.96]). Stratification analysis of
      ethnicity in this meta-analysis indicated that rs2292832 polymorphism decreased
      the risk of GC among Caucasians (TT  + TC vs. CC, dominant model: OR and 95% CI,
      0.69 (0.50,0.97); TC vs. CC, heterozygote model: OR and 95% CI, 0.68
      [0.47,0.97]), while this SNP increased the risk of GC among Asians (TT vs. TC  +
      CC, recessive model: OR and 95% CI, 1.24 [1.04,1.48]; T vs. C, allele model: OR
      and 95% CI, 1.13 [1.00,1.28]). CONCLUSION: This case-control study and meta
      analysis confirm that miR-149 gene rs2292832 polymorphism is associated with
      increased risk of GC among Asians.

PMID- 30274914
TI  - Selenium and selenoproteins in (redox) signaling, diseases, and animal models -
      200 year anniversary issue.

PMID- 30274915
TI  - [New guidelines on dyslipidemia management: Comparison of French (HAS) and
      European (ESC/EAS) guidelines].
AB  - Total cardiovascular risk estimation using a system such as SCORE is recommended
      for adults>40years of age without evidence of cardiovascular disease, diabetes,
      chronic kidney disease, severe hypertension or familial hypercholesterolemia.
      Before treatment, a full lipid profile is recommended, fasting in French
      guidelines, fasting or non-fasting in European guidelines. LDL-C has to be used
      as the primary target for treatment. For patients with elevated triglycerides,
      non-HDL-C level is also recommended as the secondary goal for treatment. In
      patients at very high and high cardiovascular risk, LDL-C goals are respectively
      below<0.70g/L and<1.0g/L. For subjects at very high and high cardiovascular risk,
      French guidelines do not mention that a>=50% reduction in LDL-C should be
      achieved. Statins are the treatment of choice to reach LDL-C goals. If the goal
      is not reached on maximally tolerated dose of statin, combination with another
      LDL lowering drug, mainly ezetimibe, is recommended. Fibrates are mainly proposed
      for patients with severe hypertriglyceridemia (TG>5g/L after lifestyle changes).

PMID- 30274916
TI  - [Challenges in the management of amiodarone-induced thyrotoxicosis].
AB  - Amiodarone, a benzofuranic iodine-rich pan antiarrhythmic drug, is frequently
      associated with thyroid dysfunction. This side effect is heterogeneous and
      unpredicted, motivating regular evaluation of thyroid function tests. In contrary
      to hypothyroidism, amiodarone-induced thyrotoxicosis (AIT) is a challenging
      situation owing to the risk of deterioration of the general and cardiac status of
      such debilitating patients. Classically, AIT is either an iodine-induced
      thyrotoxicosis in patients with an abnormal thyroid (type I), or due to a
      subacute thyroiditis on a "healthy" thyroid (type II). Even if many studies tried
      to better identify the types of AIT, the diagnostic dilemma of type of AIT could
      be present, and many patients are treated by an association of antithyroid drugs
      (useful for type I AIT) with corticoids (useful for type II AIT). Being the main
      etiological factor in AIT, amiodarone is supposed to be stopped, but it could
      remain the only anti-arrhythmic option that is needed to be either continued or
      reintroduced to improve the cardiovascular survival. Recently, many studies
      demonstrated that amiodarone could be continued or reintroduced in patients with
      history of type II AIT. Nevertheless, in the other patients, amiodarone
      maintenance complicates the therapeutic response to the antithyroid drugs and
      increases the risk of AIT recurrence. Thus, amiodarone therapy is preferred to be
      interrupted. In such patients, thyroid ablation is recommended once AIT is under
      control.

PMID- 30274917
TI  - Identification of 34 novel mutations in propionic acidemia: Functional
      characterization of missense variants and phenotype associations.
AB  - Propionic acidemia (PA) is caused by mutations in the PCCA and PCCB genes,
      encoding alpha and beta subunits, respectively, of the mitochondrial enzyme
      propionyl-CoA carboxylase (PCC). Up to date, >200 pathogenic mutations have been
      identified, mostly missense defects. Genetic analysis in PA patients referred to
      the laboratory for the past 15 years identified 20 novel variants in the PCCA
      gene and 14 in the PCCB gene. 21 missense variants were predicted as probably
      disease-causing by different bioinformatics algorithms. Structural analysis in
      the available 3D model of the PCC enzyme indicated potential instability for most
      of them. Functional analysis in a eukaryotic system confirmed the pathogenic
      effect for the missense variants and for one amino acid deletion, as they all
      exhibited reduced or null PCC activity and protein levels compared to wild-type
      constructs. PCCB variants p.E168del, p.Q58P and p.I460T resulted in medium-high
      protein levels and no activity. Variants p.R230C and p.C712S in PCCA, and
      p.G188A, p.R272W and p.H534R in PCCB retained both partial PCC activity and
      medium-high protein levels. Available patients-derived fibroblasts carriers of
      some of these mutations were grown at 28  degrees C or 37  degrees C and a slight
      increase in PCC activity or protein could be detected in some cases at the
      folding-permissive conditions. Examination of available clinical data showed
      correlation of the results of the functional analysis with disease severity for
      most mutations, with some notable exceptions, confirming the notion that the
      final phenotypic outcome in PA is not easily predicted.

PMID- 30274918
TI  - New Diabetes Canada Clinical Practice Guidelines for Diabetes and Pregnancy -
      What's Changed?

PMID- 30274919
TI  - A case of Erdheim-Chester disease with spinal cord compression and sphenoid sinus
      involvement.
AB  - Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis. It
      is an inflammatory disorder associated with BRAF V600E mutation in 50% of cases.
      This multisystem disease is rarely associated with spinal involvement.
      Neurological involvement is an independent predictive factor of poor prognosis.
      The diagnosis is histopathological based on CD68-positive and CD1A-negative
      histiocytes. Treatment with interferon-alpha is an independent predictor of
      survival in Erdheim-Chester disease and vemurafenib has also been shown to be
      effective for BRAF V600E mutation. We report a clinical case of a 51-year-old
      patient with multiple and rare locations of Erdheim-Chester disease, particularly
      at the sphenoid sinus.

PMID- 30274920
TI  - Composite Health Outcomes in Pediatric and Young Adult Kidney Transplant
      Recipients.
AB  - OBJECTIVE: To assess composite health outcomes in pediatric and young adult
      kidney transplant recipients following kidney transplantation. STUDY DESIGN: We
      conducted a cross-sectional study of all recipients at our center who had a 1-, 3
      , 5-, and/or 10-year transplant anniversary visit between October 2008 and
      February 2015. The kidney transplant recipients were assessed at each time point
      according to an outcome measure consisting of 15 pass/fail criteria in 5 domains:
      allograft health, rejection and immunology, infection, cardiovascular health, and
      growth. RESULTS: We analyzed 148 patients at 231 transplantation anniversary
      visit time points; 52 of 82 (63%) patients assessed at 1 year had an ideal
      outcome, meeting at least 13 of the 15 criteria. This decreased to 37% at year 3,
      40% at year 5, and 26% at year 10 (P < .01). The most common failures across all
      time points occurred in the domains of growth (43%-52% passing) and
      cardiovascular health (33%-51% passing). Allograft health declined significantly,
      decreasing from 74% at year 1 to 33% at year 10 (P < .01). The percentage of
      patients with graft failure increased from 2.4% at 1 year to 39.5% at 10 years (P
      < .01), and patient deaths increased from 0 to 11% (P < .01) in the same time
      frame. CONCLUSIONS: Ideal outcomes for pediatric kidney transplant recipients
      decrease over time with growth, cardiovascular health, and allograft health as
      the primary failure modes. Understanding the composite health of young recipients
      will allow primary care providers and nephrologists alike to evaluate the overall
      health of kidney transplant recipients and focus clinical care on the most common
      sequelae.

PMID- 30274921
TI  - Persistent Facial Swelling in an 8-Year-Old.

PMID- 30274922
TI  - Longitudinal Associations between Neurodevelopment and Psychosocial Health Status
      in Patients with Repaired D-Transposition of the Great Arteries.
AB  - OBJECTIVE: To examine associations between measurements of neurodevelopment and
      psychosocial health status at age 8 and 16 years in patients with repaired dextro
      transposition of the great arteries. STUDY DESIGN: In the 16-year follow-up of
      the Boston Circulatory Arrest Study, 137 parents completed the Child Health
      Questionnaire-Parent Form-50, of whom 135 had completed the Child Health
      Questionnaire-Parent Form-50 when their child was age 8 years. Psychosocial and
      physical summary scores were used to assess change in health status from age 8 to
      16 years. A comprehensive battery of neurodevelopmental testing was performed at
      ages 8 and 16 years to examine associations with adolescent health status.
      RESULTS: Lower psychosocial summary scores of 16 year old subjects with dextro
      transposition of the great arteries were highly associated with numerous
      concurrent domains of neurodevelopmental function, most notably with higher
      (worse) scores on the Conners' Attention Deficit Hyperactivity
      Disorder/Diagnostic and Statistical Manual-4th Edition Scales (parent: r = -0.62,
      P <.001; adolescent: r = -0.43, P < .001) and the Behavior Rating Inventory of
      Executive Function Global Executive Composite (parent: r = -0.66, P <.001;
      adolescent: r = -0.39, P <.001). Psychosocial and physical summary scores tracked
      from ages 8 to 16 years (r = 0.44 and 0.47, respectively, P <.001 for each).
      Higher (worse) scores of multiple attention measures at age 8 years predicted
      worse psychosocial summary scores at age 16 years. CONCLUSIONS: Attention
      deficits at age 8 years were highly predictive of worse psychosocial health
      status in adolescence. Further studies are needed to assess whether treatment of
      childhood attention deficit hyperactivity disorder could improve adolescent well
      being.

PMID- 30274923
TI  - Opioid Prescribing Practices for Pediatric Headache.
AB  - OBJECTIVES: To characterize the frequency of opioid prescribing for pediatric
      headache in both ambulatory and emergency department (ED) settings, including
      prescribing rates by provider type. STUDY DESIGN: A retrospective cohort study of
      Washington State Medicaid beneficiaries, aged 7-17 years, with an ambulatory care
      or ED visit for headache between January 1, 2012, and September 30, 2015. The
      primary outcome was any opioid prescribed within 1 day of the visit. RESULTS: A
      total of 51 720 visits were included, 83% outpatient and 17% ED. There was a
      predominance of female (63.2%) and adolescent (59.4%) patients, and 30.5% of
      encounters involved a pediatrician. An opioid was prescribed in 3.9% of ED and
      1.0% of ambulatory care visits (P < .001). Pediatricians were less likely to
      prescribe opioids in both ED (-2.70 percentage point; 95% CI, -3.53 to -1.88) and
      ambulatory settings (-0.31 percentage point; 95% CI, -0.54 to -0.08; P < .001).
      CONCLUSIONS: Opioid prescribing rates for pediatric headache were low, but
      significant variation was observed by setting and provider specialty. We
      identified opioid prescribing by nonpediatricians as a potential target for
      quality improvement efforts.

PMID- 30274924
TI  - Intravenous Immunoglobulin Versus Anti-D Immunoglobulin: When Better Treatment
      May Not Be the Best Treatment.

PMID- 30274925
TI  - All Aboard Meal Train: Can Child-Friendly Menu Labeling Promote Healthier Choices
      in Hospitals?
AB  - OBJECTIVE: To evaluate patient meal orders and consumption with a revised menu
      design that includes child-friendly labeling. STUDY DESIGN: A randomized
      controlled trial among hospitalized children was performed over a 1-month period
      comparing the control menu layout and the intervention menu. The intervention
      menu contained the same choices but was labeled to encourage healthy eating.
      Children on a specialized diet, receiving parenteral nutrition, or age <2 years
      were excluded. RESULTS: A total of 163 patients (81 males) were included, with a
      mean age of 9.9 +/- 5.1 year, and a mean weight z-score of -0.08 +/- 1.3.
      Children receiving the intervention ordered more "green-light" healthy choices
      and fewer "red-light" items, with 0.65 lower odds of selecting a red-light item
      (95% CI, 0.55-0.76) and 1.75 higher odds of selecting a green-light item (95% CI,
      1.49-2.04), both at the first meal, but with effects waning over time. There were
      trends toward increased intake of fruits and vegetables and decreased intake of
      "foods to limit", but no impact on the consumption of sugar-sweetened beverages.
      Both intervention and control group consumed their meals in equal proportions.
      CONCLUSIONS: The combination of menu labeling techniques targeted to children in
      the inpatient hospital setting was an effective short-term tool for increasing
      the intake of healthier foods, although the effect of labeling waned over time.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT02692001.

PMID- 30274926
TI  - Racial and Ethnic Disparities in the Use of Mother's Milk Feeding for Very Low
      Birth Weight Infants in Massachusetts.
AB  - OBJECTIVE: To examine the extent to which maternal race/ethnicity is associated
      with mother's milk use among hospitalized very low birth weight (VLBW) infants
      and maternal receipt of hospital breastfeeding support practices (human milk
      prenatal education, first milk expression <6 hours after delivery, lactation
      consultation <24 hours, any skin-to-skin care <1 month). STUDY DESIGN: We studied
      1318 mother-VLBW infant pairs in 9 Massachusetts level 3 neonatal intensive care
      units (NICUs) between January 2015 and November 2017. We estimated associations
      of maternal race/ethnicity with any and exclusive mother's milk on day 7, on day
      28, and at discharge/transfer and hospital practices. We estimated HRs comparing
      the probability of continued milk use over the hospitalization by race/ethnicity
      and tested mediation by hospital practices, adjusting for birth weight and
      gestational age and including hospital and plurality as random effects. RESULTS:
      Mothers were 48% non-Hispanic white, 21% non-Hispanic black, and 20% Hispanic.
      Initiation of mother's milk was similar across groups, but infants of Hispanic
      mothers (hazard ratio [HR], 2.71; 95% CI, 2.05-3.59) and non-Hispanic black
      mothers (HR, 1.55; 95% CI, 1.17-2.07) stopped receiving milk earlier in the
      hospitalization compared with infants of non-Hispanic white mothers. Hispanic
      mothers had lower odds of providing skin-to-skin care at <1 month (OR, 0.61; 95%
      CI, 0.43-0.87) compared with non-Hispanic whites. CONCLUSIONS: Hispanic and non
      Hispanic black mothers were less likely than non-Hispanic white mothers to
      continue providing milk for their VLBW infants throughout the NICU stay.

PMID- 30274927
TI  - Mycoplasma pneumoniae-Induced Red Fingers.

PMID- 30274928
TI  - Daily Intake of Soft Drinks and Moderate-to-Severe Acne Vulgaris in Chinese
      Adolescents.
AB  - OBJECTIVES: To investigate the association of soft drink consumption and the
      intake of sugar from soft drinks with the prevalence of acne in adolescents.
      STUDY DESIGN: This was a university-based epidemiologic investigation that
      included 8226 students who underwent health examinations and a questionnaire
      survey inquiring about the intake of soft drinks. Skin diseases were diagnosed by
      certificated dermatologists during the health examination. Two-level logistic and
      generalized additive models were used to estimate the associations, and aORs were
      presented as the effect size. RESULTS: A total of 8197 student survey responses
      were analyzed. Frequent intake (>=7 times per week) of carbonated sodas (aOR
      1.61, 95% CI 0.96-2.72), sweetened tea drinks (aOR 2.52, 95% CI 1.43-4.43), and
      fruit-flavored drinks (aOR 1.90, 95% CI 1.18-3.07) was associated with moderate
      to-severe acne after adjustments for confounders. The occasional intake of fruit
      flavored drinks (1-2 times per week) had a weak protective effect on acne (aOR
      0.86, 95% CI 0.74-0.99). The intake of sugar from any soft drinks showed a
      nonlinear association with acne (P < .01), and sugar intake >=100 g/d was
      significantly associated with moderate-to-severe acne (aOR 3.12, 95% CI 1.80
      5.41). CONCLUSIONS: Daily soft drink consumption significantly increases the risk
      of moderate-to-severe acne in adolescents, especially when the sugar intake from
      any type of soft drink exceeds 100 g per day.

PMID- 30274929
TI  - Pleural effusions of urinary etiologies.

PMID- 30274930
TI  - Abdominal etiologies of pleural effusion.

PMID- 30274931
TI  - Obstetric and gynecologic causes of pleural effusions.
AB  - Obstetric and gynecologic pleural effusions may occur in the setting of different
      diseases and conditions, early and appropriate recognition of the different
      etiologies of these effusions will aid in appropriate treatment management. In
      this paper we will give an overview of the different pleural effusion etiologies
      that may be encountered including catamenial hemothorax, ovarian hyperstimulation
      syndrome, the different Meigs' syndromes and benign peripartum pleural effusion.

PMID- 30274932
TI  - The immune cell infiltrate in the microenvironment of vulvar Paget disease.
AB  - BACKGROUND: Non-invasive vulvar Paget disease (VPD) is a rare skin disorder
      mainly affecting elderly women. Recently, the immune modulator imiquimod was
      reported as an effective treatment option. Knowledge about the immune
      microenvironment of VPD is lacking. METHODS: This study investigates the basic
      characteristics of the immune infiltrate in VPD (n = 10); moreover the influence
      of imiquimod was studied (n = 6). Immunohistochemistry for CD4, CD8, CD14, CD20,
      CD56 and FoxP3 was performed. The infiltrates of VPD were compared to vulvar high
      grade squamous cell intraepithelial lesions (HSIL) (n = 43), a HPV induced vulvar
      premalignancy with known response to imiquimod cream, and healthy controls (n =
      30). Immune cell counts in samples taken before and after treatment were
      compared. RESULTS: The microenvironment in VPD differs from the healthy vulvar
      skin and vulvar HSIL. VPD is characterized by a decrease in immune cells in the
      epithelium and an abundant number of immune cells in the stroma, consisting
      predominantly of T cells. The intraepithelial CD8+/Foxp3+ ratio and number of
      CD56+ increased after imiquimod therapy, whereas the numbers of CD14+ cells
      decreased which may point to a treatment-induced type 1 immune response.
      CONCLUSIONS: The epithelium in VPD contains less immune cells, but a dense
      stromal immune infiltrate. Changes in immune cell counts after immune modulation
      in relation to clinical responses should be further investigated.

PMID- 30274933
TI  - CDKN2A germline mutations are not associated with poor survival in an Italian
      cohort of melanoma patients.
AB  - BACKGROUND: Cyclin dependent kinase inhibitor 2A gene (CDKN2A) germline mutations
      have recently been associated with poor survival in patients with melanoma.
      Despite the high mutation rate in our cohort (up to 10% in patients with
      apparently sporadic melanoma), information on the impact of CDKN2A on survival in
      this cohort is lacking. OBJECTIVE: To investigate whether poor survival
      associated with CDKN2A germline mutations was confirmed in a high mutation
      prevalence cohort of Italian patients with melanoma undergoing a mutation-based
      follow-up. METHODS: A total of 1239 patients with cutaneous melanoma were tested
      for CDKN2A mutational status and then assigned to a follow-up scheme according
      not only to family history but also to CDKN2A mutational status, as follow-up
      intervals were more frequent for CDKN2A germline mutation-positive (MUT+)
      patients. From this cohort, we selected 106 MUT+ patients (with familial melanoma
      or apparently sporadic melanoma) and 199 CDKN2A germline mutation-negative (MUT-)
      patients with sporadic melanoma who were matched by age and sex and had a similar
      tumor stage distribution. RESULTS: We found no difference in overall survival
      (hazard ratio, 0.85; 95% confidence interval, 0.48-1.52; P = .592,) or melanoma
      specific survival (hazard ratio, 0.86; 95% confidence interval, 0.38-1.95; P =
      .718,) between MUT+ and MUT- patients. MUT+ patients were more likely to develop
      multiple melanomas and to undergo surgical excision of dysplastic nevi than were
      MUT- patients. LIMITATIONS: Retrospective study. CONCLUSION: CDKN2A mutations
      were not associated with survival in our cohort.

PMID- 30274934
TI  - The POWER-tool: Recommendations for involving patient representatives in choosing
      relevant outcome measures during rare disease clinical trial design.
AB  - In clinical trials, it is relevant to ask patients and/or their caregivers which
      aspects concerning their disease they consider important to measure when a new
      intervention is being investigated. Those aspects, useful as outcome measures in
      a trial, are of pivotal importance for the result of the trial and the subsequent
      decision-making. In rare diseases the choice of outcome measures may be even more
      important, due to the small numbers and heterogeneity of the patients that are
      included. We have developed a tool to involve patients in the determination of
      outcome measures and the choice of measurement instruments. This tool was
      developed together with a patient think tank, consisting of a group of rare
      disease patient representatives, and by interviewing end users. We have road
      tested our tool in an ongoing trial, and evaluated it during a focus group
      meeting. The tool consists of three steps: 1) Preparation, 2) Consultation of
      patients, 3) Follow-up during which the consultation results are implemented in
      the trial design. The tool provides guidelines for researchers to include the
      patient's opinion in the choice of outcome measures in the trial design stage. We
      describe the development of the POWER-tool (Patient participation in Outcome
      measure WEighing for Rare diseases), and first experiences of the tool in an
      ongoing trial.

PMID- 30274935
TI  - Voluntary associations and co-production of health promoting activities for older
      adults: Experiences and policy lessons from Denmark.
AB  - Demographic transitions in Europe accentuate the need to develop innovative
      solutions for healthy ageing. One increasingly popular policy approach is co
      production between local governments and voluntary community associations (VCOs)
      to promote activities for health and wellbeing among older adults. While co
      production has been studied from the perspective of local governments there is
      limited knowledge regarding how voluntary associations perceive their conditions.
      This study aims to fill this gap using survey data from voluntary associations in
      Denmark. The investigation is based on an electronic survey (n = 263) of VCOs
      engaged in activities relevant for healthy ageing in three Danish municipalities.
      The survey addressed 13 issues and potential problems within four categories -
      ''members and volunteers', 'economics, 'media and the public' and ''politics and
      the local government'. The paper presents a relatively positive picture of the
      potentials in municipal-VCO collaboration. However, we also find that a sizeable
      number of VCOs point to problems and obstacles particular in regards to
      recruitment of members and economics. While the municipalities in our study have
      all developed strategies to support VCOs and to promote coproduction it seems
      that there are deficits in the implementation of the strategies. This leads us to
      conclude that municipalities must pay close attention to the issues and
      conditions for VCOs in order to succeed with their policy initiatives in this
      area.

PMID- 30274936
TI  - Assessing quality of primary diabetes care in South Korea and Taiwan using
      avoidable hospitalizations.
AB  - Quality of primary diabetes care is a key health policy concern in many OECD
      countries with an aging population. This cross-national, population-based study
      examined the extent and attributes of diabetes-related avoidable hospitalizations
      (DRAHs) in South Korea and Taiwan, both of which have social health insurance
      based health systems with limited gate-keeping for hospitalizations. We analyzed
      comparable, nationally representative health insurance beneficiary datasets for
      the two countries (2002-2013), linked with community health resource data. The
      age- and sex-standardized DRAH rates were calculated, and multivariate, multi
      level longitudinal modeling approaches were adopted. The DRAH rate decreased in
      Taiwan consistently during 2002-2013 and in Korea after 2011 only. Under the
      universal health coverage, people enjoyed high accessibility to care. A higher
      number of physician visits reduced DRAHs in Korea but not in Taiwan. Socio
      economic disparities in DRAHs still existed in both countries, especially in
      Taiwan. We found a different trajectory in two similar health systems for the
      selected health system performance indicator for primary diabetes care. This can
      be partly explained by different policy approaches to diabetes management in the
      two countries over the years. Necessary are policy efforts to improve the quality
      and equality of primary diabetes care and better control of hospital admissions
      in these two health systems that provide generous access to care at a low cost in
      East Asia.

PMID- 30274937
TI  - Working capital management policy in health care: The effect of leverage.
AB  - Hospitals, which are mainly capital intensive, require large amounts of financial
      resources to render high-quality services. Accordingly, health care managers and
      policy makers should take into account the level of debt in managing working
      capital. This study, therefore, aims to explore whether the financial leverage
      moderates the relationship between the working capital and profitability for the
      publicly-listed European Hospitals. The data set including 52 hospitals with 468
      observations was solicited from the ORBIS. A regression analysis was carried out.
      The results reveal that increasing the length of the cash conversion cycle for
      hospitals with high financial leverage decreases profitability. On the contrary,
      increasing the length of the cash conversion cycle for the ones having low
      leverage boosts profitability. The findings of this study suggest that since
      leverage influences the relationship between the cash conversion cycle and
      profitability, the degree of financial leverage is an important indicator to be
      considered by health care managers and policy makers in managing working capital.
      In addition, by clarifying the effect of leverage, this study helps policy makers
      understand and estimate the possible impact of working capital changes on
      profitability. This study also helps managers and decision makers not only apply
      a tight working capital policy but also decide whether to increase or decrease
      the length of cash conversion cycle to improve hospital profitability.

PMID- 30274938
TI  - Hemodynamic and clinical performance of Solo stentless bioprosthetic aortic
      valves.
AB  - OBJECTIVE: To report the hemodynamic profile and short- and medium-term outcomes
      of Freedom Solo and Solo Smart stentless aortic valves implanted at our center.
      METHODS: Between 2009 and 2015, all patients undergoing aortic valve replacement
      using Solo stentless valves at our center were enrolled. Clinical and
      echocardiographic follow-up was carried out six months postoperatively. Survival
      and major events, including structural valve deterioration and non-structural
      valve dysfunction, endocarditis, reoperation and stroke, were assessed through
      medical records or telephone interview with the referring cardiologist up to
      November 2015 (mean and maximum follow-up 39+/-22 and 78 months, respectively).
      RESULTS: Patients' (n=345) mean age was 72+/-8 years, 52% were female and median
      euroSCORE II was 2.7 (1.5-4.7). There was no intraoperative mortality and in
      hospital mortality was 2.6%. Postoperatively, mean transvalvular gradient was
      11.9+/-4.5 mmHg and effective orifice area was 1.9+/-0.5 cm2. Patient-prosthesis
      mismatch occurred in 14% but was severe in only one patient. Cumulative survival
      at six years was 72%. Six patients were reoperated: three due to endocarditis,
      two for structural prosthesis deterioration and one because of periprosthetic
      fistula. Five patients suffered stroke, three had medically-treated endocarditis
      and one had structural valve deterioration but was not considered suitable for
      reoperation. None of the remainder had structural valve deterioration or non
      structural valve dysfunction. CONCLUSIONS: Solo stentless aortic valves are safe
      to implant, with promising clinical outcomes in short- and medium-term
      assessment. Moreover, they show an excellent hemodynamic performance: low
      transvalvular gradients, large effective orifice areas and low incidence of
      patient-prosthesis mismatch.

PMID- 30274940
TI  - Design and synthesis of thiazolylhydrazone derivatives as inhibitors of
      chitinolytic N-acetyl-beta-d-hexosaminidase.
AB  - N-acetyl-beta-d-hexosaminidase (Hex) is potential target for pesticide design.
      Here, a series of thiazolylhydrazone derivatives were designed, synthesized and
      evaluated as competitive inhibitors of OfHex1, a Hex from the agricultural pest
      Ostrinia furnacalis. The derivative 3k, with a (benzyloxy)methyl group at the N3
      atom, demonstrated greater potency with a Ki of 10.2 uM. Molecular docking
      analysis indicated that the (benzyloxy)methyl group of 3k was bound to a
      previously unexplored pocket formed by Loop478-496. Then further optimization
      around naphthalene ring led to find the more potency substituent phenyl. The
      derivative 7, with phenoxyethyl group at R1 and a phenyl group at R2,
      demonstrated an augmented potency with a Ki of 2.1 uM. Molecular docking analysis
      indicated that 7 was bound to the active pocket of OfHex1 more favorably than 3k.
      This work suggests a novel scaffold for developing specific Hex inhibitors.

PMID- 30274939
TI  - Identification of DK419, a potent inhibitor of Wnt/beta-catenin signaling and
      colorectal cancer growth.
AB  - The Wnt signaling pathway is critical for normal tissue development and is an
      underlying mechanism of disease when dysregulated. Previously, we reported that
      the drug Niclosamide inhibits Wnt/beta-catenin signaling by decreasing the
      cytosolic levels of Dishevelled and beta-catenin, and inhibits the growth of
      colon cancers both in vitro and in vivo. Since the discovery of Niclosamide's
      anthelmintic activity, a growing body of literature indicates that Niclosamide is
      a multifunctional drug. In an effort to identify derivatives of Niclosamide with
      improved pharmacokinetic properties that maintain the multifunctional drug
      activity of Niclosamide for clinical evaluation, we designed DK419, a derivative
      containing a 1H-benzo[d]imidazole-4-carboxamide substructure, using the structure
      activity relationships (SAR) of the Niclosamide salicylanilide chemotype. Similar
      to Niclosamide, we found DK419 inhibited Wnt/beta-catenin signaling, altered
      cellular oxygen consumption rate and induced production of pAMPK. Moreover, we
      found DK419 inhibited the growth of CRC tumor cells in vitro, had good plasma
      exposure when dosed orally, and inhibited the growth of patient derived CRC240
      tumor explants in mice dosed orally. DK419, a derivative of Niclosamide with
      multifunctional activity and improved pharmacokinetic properties, is a promising
      agent to treat colorectal cancer, Wnt-related diseases and other diseases in
      which Niclosamide has demonstrated functional activity.

PMID- 30274941
TI  - A novel 2,4-diaminopyrimidine derivative as selective inhibitor of protein kinase
      C theta prevents allograft rejection in a rat heart transplant model.
AB  - Protein kinase C theta (PKCtheta) plays a critical role in T cell signaling and
      is an attractive target for the treatment of T cell-mediated diseases such as
      transplant rejection and autoimmune disease. To identify PKCtheta inhibitors, we
      focused on the 2,6-diamino-3-carbamoyl-5-cyanopyrazine derivative 2, which
      exhibited moderate PKCtheta inhibitory activity. Optimization of 2 identified the
      2,4-diamino-5-cyanopyrimidine derivative 16c, which exhibited potent PKCtheta
      inhibitory activity and showed good selectivity against other PKC isozymes.
      Compound 16c prolonged graft survival in an in vivo rat heterotopic cardiac
      transplant model.

PMID- 30274943
TI  - Marijuana Use During Pregnancy.

PMID- 30274942
TI  - Impact of weekend treatment on short-term and long-term survival after urgent
      repair of ruptured aortic aneurysms in Germany.
AB  - OBJECTIVE: There is some evidence that weekend admission to the hospital is
      associated with worse outcomes compared with weekday admission. However, only a
      few studies have focused on weekend vs weekday surgery outcomes. This study aimed
      to determine whether there is a weekend effect on outcomes in the treatment of
      ruptured aortic aneurysms in Germany. METHODS: Health insurance claims of
      Germany's third largest insurance provider, DAK-Gesundheit, were used to
      investigate short-term and long-term mortality after weekend vs weekday treatment
      of ruptured aortic aneurysm. Patients undergoing endovascular repair (ER) or open
      surgical repair (OSR) between January 2008 and December 2016 were included in the
      study. Both propensity score matching and regression methods were used to adjust
      for confounding. RESULTS: There were 1477 patients in the cohort, of whom 517
      (35.0%) underwent ER and 960 (65.0%) OSR. Overall, 995 (67.4%) patients underwent
      an operation on weekdays (Monday to Thursday), and 482 (32.6%) patients underwent
      an operation on a weekend (Friday to Sunday). In multivariable models, patients
      who underwent an operation on a weekend were at higher risk of in-hospital death
      after OSR (49.2% vs 38.0%; odds ratio [OR], 1.61; P = .001), and there was a
      trend toward higher in-hospital mortality after ER (29.5% vs 21.2%; OR, 1.55; P =
      .056). The ER of thoracic or thoracoabdominal aortic ruptures was associated with
      significantly higher in-hospital mortality compared with ER of abdominal aortic
      aneurysm (OR, 1.69; P = .026). CONCLUSIONS: Weekend repairs of ruptured aortic
      aneurysms are associated with worse in-hospital survival compared with weekday
      surgery. ER of thoracic or thoracoabdominal aortic ruptures is associated with
      worse in-hospital survival compared with ER of ruptured abdominal aortic
      ruptures. This might be an international phenomenon requiring joint learning and
      action in times of centralization of aortic procedures.

PMID- 30274944
TI  - Women's Cardiovascular Health.

PMID- 30274945
TI  - Psychiatric comorbidity in multiple sclerosis.
AB  - AIM: To study the prevalence of psychiatric comorbidities in patients of multiple
      sclerosis and their association to the degree of disability. METHOD: Psychiatric
      symptoms were assessed in 90 patients of multiple sclerosis using GHQ-12, MMSE,
      HADS, Beck Depression Inventory and AUDIT. Neurological disability was assessed
      using Expanded Disability Status Scale. Correlations were determined between EDSS
      scores and psychiatric scale scores. RESULT: 61% of patients had significant
      psychological distress. Depression was most common (38.8%) which was followed by
      anxiety symptoms (27.8%). Cognitive functioning was relatively intact in patients
      with mild to moderate neurological disability. Alcohol abuse was mostly
      restricted to male gender. CONCLUSION: Psychiatric illness is highly prevalent in
      patients of multiple sclerosis leading to poor quality of life and significant
      distress. Psychiatric disability was higher in patients who had greater
      deterioration in neurological function. All cases of MS should be assessed for
      psychiatric morbidities as can be alleviated by appropriate intervention.

PMID- 30274946
TI  - Emergency Medical Services Use Among Patients Receiving Involuntary Psychiatric
      Holds and the Safety of an Out-of-Hospital Screening Protocol to "Medically
      Clear" Psychiatric Emergencies in the Field, 2011 to 2016.
AB  - STUDY OBJECTIVE: Patients with acute psychiatric emergencies who receive an
      involuntary hold often spend hours in the emergency department (ED) because of a
      deficit in inpatient psychiatric beds. One solution to address the lack of prompt
      psychiatric evaluation in the ED has been to establish regional stand-alone
      psychiatric emergency services. However, patients receiving involuntary holds
      still need to be screened and evaluated to ensure that their behavior is not
      caused by an underlying and life-threatening nonpsychiatric illness. Although
      traditional regional emergency medical services (EMS) systems depend on the
      medical ED for this function, a field-screening protocol can allow EMS to
      directly transport a substantial portion of patients to a stand-alone psychiatric
      emergency service. The purpose of this investigation is to describe overall EMS
      use for patients receiving involuntary holds, compare patients receiving
      involuntary holds with all EMS patients, and evaluate the safety of field medical
      clearance of an established field-screening protocol in Alameda County, CA.
      METHODS: We obtained data for all EMS encounters between November 1, 2011, and
      November 1, 2016, using Alameda County's standardized data set. After unique
      patient identification, we describe the data at the patient level and at the
      encounter level. At the patient level, we compare "involuntary hold patients"
      (>=1 involuntary hold during the study period) with those who were "never held."
      Additionally, we assess the safety of out-of-hospital medical clearance by
      calculating the rate of failed diversion, defined as retransport of a patient to
      a medical ED within 12 hours of transport to the psychiatric emergency services
      by EMS. RESULTS: Of the 541,731 total EMS encounters in Alameda County during the
      study period, 10% (N=53,887) were identified as involuntary hold encounters. Of
      these involuntary hold patient encounters, 41% (N=22,074) resulted in direct
      transport of the patient to the stand-alone psychiatric emergency service for
      evaluation; 0.3% (N=60) failed diversion and required retransport within 12
      hours. At the patient level, Alameda County EMS encountered 257,625 unique
      patients, and 10% (N=26,283) had at least one encounter for an involuntary hold
      during the study period. These "involuntary hold patients" were substantially
      younger, more likely to be men, and less likely to be insured. Additionally, they
      had higher overall EMS use: "involuntary hold patients" accounted for 24% of all
      encounters (N=128,003); 53,887 of these encounters were for involuntary holds,
      whereas an additional 74,116 were for other reasons. Similarly, 4% of
      "involuntary hold patients" had 20 or more encounters, whereas only 0.4% of
      "never held" patients were in this category. Last, the 7% of "involuntary hold
      patients" (N=1,907) who received greater than or equal to 5 involuntary holds
      during the study period accounted for 39% of all involuntary holds and 9% of all
      EMS encounters. CONCLUSION: Ten percent of all EMS encounters were for
      involuntary psychiatric holds. With an EMS-directed screening protocol, 41% of
      all such patient encounters resulted in direct transport of the patient to the
      psychiatric emergency service, bypassing medical clearance in the ED. Overall,
      only 0.3% of these patients required retransport to a medical ED within 12 hours
      of arrival to psychiatric emergency services. We found that 24% of all EMS
      encounters in Alameda County were attributable to "involuntary hold patients,"
      reinforcing the importance of the effects of mental illness on EMS use.

PMID- 30274947
TI  - Cumulative Long-Term Incidence of Postoperative Periprosthetic Femoral Fractures
      Using an Uncemented Tapered Titanium Hip Stem: 26- to 32-Year Results.
AB  - BACKGROUND: Although falling is becoming a major problem in the elderly, little
      is known about the long-term incidence of postoperative periprosthetic femoral
      fractures (PFF) after total hip arthroplasty (THA) using uncemented stems with a
      minimum follow-up of 26 years postoperatively. METHODS: In a consecutive series,
      the cumulative incidence of PFF after uncemented THA using a straight,
      collarless, tapered titanium stem was retrospectively reviewed in 354 hips (326
      patients). After a mean follow-up of 28 (26-32) years postoperatively, 179 hips
      had died and 5 hips had been lost to follow-up. Kaplan-Meier survival analysis
      was used to estimate cumulative percentage probability of PFF. RESULTS: At final
      follow-up, a total of 27 fractures in 27 patients had occurred. In 15 hips, the
      stem had to be revised, and in 10 the fracture was treated by open reduction and
      internal fixation. Two patients declined further surgery. The cumulative
      percentage probability of PFF was 1.6% (95% confidence interval, 0.7 to 3.8) at
      10 years and 13.2% (95% confidence interval, 8.5 to 20.2) at 29 years after
      primary THA. There was no association between the occurrence of fracture and
      gender, age at primary THA, cup revision, or canal fill index. CONCLUSION: Our
      findings indicate that PFF is the major mode of failure in the long term after
      uncemented THA using a tapered titanium stem. More research is needed to evaluate
      the reasons and risk factors for PFF after THA, thus providing better prophylaxis
      for those at risk and to compare the long-term incidence using different fixation
      methods and implants. LEVEL OF EVIDENCE: IV.

PMID- 30274948
TI  - Medical student education in transfusion medicine: Proposal from the "European
      and Mediterranean initiative in transfusion medicine".
AB  - A large body of observations indicate that there is an inconsistent knowledge of
      Transfusion Medicine among health care professionals as well as inconsistent
      knowledge in all aspects of the transfusion process, from blood donation to
      transfusion on the ward. It is obvious to consider that appropriate education in
      Transfusion Medicine should be achieved in the education of specialists who will
      prescribe transfusion on a regular basis (hematologists, critical care
      specialists, anaethesiologists and others.) However,we also believe that
      education in Transfusion Medicine should also be delivered to almost all other
      medical specialists who may prescribe blood components. The variability in
      education of undergraduates in medical schools is universal most likely due to an
      absence of a predefined common platform. This paper, therefore, focuses on
      education at the undergraduate level and advocates coverage of the essential
      physiology and pathophysiology of blood as applied to blood transfusion as well
      as the medical and societal aspects of issues related to blood donation. It
      proposes incremental levels of training in Transfusion Medicine, with what is
      being therefore referred to as 'A', 'B', 'C' etc. curricula in ascending order of
      complexity; for example, 'A' and 'B' levels would involve medical, midwifery and
      nursing students, covering a broad base of the subject: they will be detailed in
      the present essay; ongoing further curricula will focus on physicians and other
      professionals working within the area or with responsibility for different
      aspects of the transfusion chain. It is intended that these courses include
      aspects of donor care, patient care and the appropriate use, safety and
      effectiveness of blood products. Next, it is advocated that curricula are
      addressed not only for high-income countries but also for middle- and low-income
      ones.

PMID- 30274949
TI  - The utility of therapeutic plasma exchange for amphotericin B overdose.
AB  - Medication error is a preventable cause of morbidity and death in the inpatient
      population. We describe a patient with an antifungal overdose treated with
      therapeutic plasma exchange (TPE). The patient was diagnosed with cryptococcal
      meningitis and received an acute overdose of amphotericin B deoxycholate instead
      of the prescribed liposomal amphotericin B. Consequently, the patient developed
      clinical symptoms including tremors, hypertension, visual hallucinations,
      vertigo, fever, and acute renal failure. A series of four TPEs was emergently
      initiated, resulting in complete resolution of most symptoms.

PMID- 30274950
TI  - Extreme lateral and interlaminar approach for intra-canal and foraminal double
      disc herniation at lumbosacral level.
AB  - INTRODUCTION AND OBJECTIVES: There are several approaches for double disc
      herniation consisting of an intracanal and foraminal lesion. Of several
      approaches, we introduced extreme lateral and interlaminar approach (ELIA). And
      we aimed to compare the approach with the conventional combined interlaminar and
      paraisthmic approach (CIPA). PATIENTS AND METHODS: The authors reviewed the
      medical charts of patients who underwent a procedure for a double disc herniation
      at the lumbosacral level between March 2012 and February 2016 and patients who
      underwent CIPA or ELIA were selected. For preoperative testing, simple X-ray,
      computed tomography (CT), and magnetic resonance imaging (MRI) scans were
      performed. For postoperative outcomes, the Korean version of the Oswestry
      Disability Index (K-ODI) and Numeric Rating Scale (NRS) at one, two, and three
      months post-operation were checked. RESULTS: Eleven patients were given ELIA and
      twenty-four patients were involved in CIPA. The mean pre K-ODI was 34.1 (+/-13.9)
      and 32.4 (+/-4.0) at each group. 1st, 2nd and 3rd month post-operative K-ODI was
      8.2 (+/-4.1), 6.4 (+/-2.1) and 5.3 (+/-2.4) in ELIA and 8.1 (+/-3.2), 7.1 (+/
      3.5) and 8.4 (+/-6.4) in CIPA. Post-operative 3rd month K-ODI showed significant
      difference between two groups (p: 0.005). The mean pre NRS was 8 (+/-0.9) and 8.6
      (+/-1.0). 1st, 2nd and 3rd month post-operative NRS was 2.4 (+/-1.5), 2.2 (+/
      1.5) and 2.0 (+/-0.9) in ELIA and 3.3 (+/-1.4), 3.3 (+/-1.6) and 3.7 (+/-1.9).
      Post-operative 3rd month NRS showed significant difference between two groups as
      well (p: 0.001). There were four (19.0%) recurrence cases in CIPA patients group,
      otherwise there was no recurrence case in ELIA group. CONCLUSIONS: In the
      treatment of L5-S1 double disc herniation, the ELIA surgical approach showed
      better outcomes than the CIPA surgical approach did with respect to pain and K
      ODI during a mid-term follow-up examination conducted three months post
      operation.

PMID- 30274951
TI  - Nested PCR for the detection of Aspergillus species in maxillary sinus samples of
      patients with chronic sinusitis.
AB  - BACKGROUND: Fungal rhinosinusitis has become an increasingly recognized disease,
      being Aspergillus species responsible for most of the cases. Its diagnosis is
      quite difficult because of the non-specific symptoms and low sensitivity of the
      current diagnostic methods. AIMS: An Aspergillus-specific nested polymerase chain
      reaction (PCR) assay using biopsy specimens taken from the maxillary sinuses was
      performed in order to assess its usefulness. Conventional diagnostic methods
      (histology and culture) were also carried out. METHODS: A case-control study was
      performed in the Institute of Stomatology, Jagiellonian University in Krakow,
      between 2011 and 2014. The case group consisted of 21 patients with suspected
      rhinosinusal mycetoma while the control group included 46 patients with no
      suspicion of fungal rhinosinusitis. The two-step PCR assay amplified an
      Aspergillus specific portion of the 18S rRNA gene. Interval estimation of
      sensitivity, specificity, positive (PPV) and negative (NPV) predictive values
      were calculated to assess the diagnostic test performance. The agreement between
      the PCR and the other tests was evaluated using the Kappa coefficient (k).
      RESULTS: Ninety percent of the samples obtained from patients diagnosed with
      mycetoma yielded positive PCR results. The PCR showed almost perfect concordance
      with histology (k=0.88). Sensitivity, specificity, PPV and NPV estimates were
      90%; 95% CI: (55.5-99.7%), 98.3%; 95% CI: (90.9-100%), 90%; 95% CI: (55.5-99.7%)
      and 98.3%; 95% CI: (90.9-100%), respectively. One clinical sample showed growth
      of Aspergillus fumigatus and positive PCR despite the negative histological
      examination. CONCLUSIONS: Nested PCR assay is a promising diagnostic tool to
      evaluate the presence of Aspergillus in the tissue of maxillary sinus from
      patients with suspicion of sinus aspergillosis.

PMID- 30274952
TI  - First isolation and molecular characterization of Cryptococcus neoformans var.
      grubii in excreta of birds in the urban perimeter of the Municipality of Popayan,
      Colombia.
AB  - BACKGROUND: Cryptococcosis is a systemic opportunistic mycosis, caused by
      Cryptococcus neoformans and Cryptococcus gattii, which affects mainly the central
      nervous system of immunocompromised patients; no reports have been made on the
      isolation of the fungus from the environment of Popayan, Colombia. AIMS: The main
      objective of this investigation was to determinate the incidence of C. neoformans
      in the urban perimeter in the City of Popayan, Colombia. METHODS: A total of 303
      samples from droppings of Columba livia and Bubulcus ibis were collected between
      September 2012 and June 2013. The samples were processed by conventional
      techniques; identification of colonies was performed by biochemical tests, and
      molecular patterns were determined by PCR fingerprinting with the primer (GTG)5
      and restriction fragment length polymorphism (RFLP) of the gene URA5. RESULTS: A
      total of 118 (38.94%) samples were positive for Cryptococcus in excreta of C.
      livia, and 361 strains belonging to Cryptococcus neoformans var. grubii were
      isolated. From the latter, 99.2% corresponded to the molecular pattern VNI and
      0.8% to VNII, with an increased occurrence (24.4%) at a temperature of 22.5
      degrees C and a humidity of 60.8%. The excreta of B. ibis did not show the
      presence of the fungus. CONCLUSIONS: C. livia excreta is a key environmental
      niche for C. neoformans var. grubii, type VNI, supporting growth and
      reproduction, and serving as a major source of infection for susceptible
      populations in Popayan. This represents the first report on the isolation of the
      agent of cryptococcosis from the environment in this region, with a significant
      prevalence in bird excreta.

PMID- 30274953
TI  - [Isolation of Hanseniaspora opuntiae from blood cultures of an immunosuppressed
      patient: An infrequent and difficult to assess finding].

PMID- 30274954
TI  - [First report of a case of fungal keratitis due to Curvularia hominis in Spain].
AB  - BACKGROUND: Dematiaceous fungal genus Curvularia is a causal agent of keratitis,
      onychomycosis, and skin infections. In 2014, using DNA sequencing techniques,
      five new species, including Curvularia hominis, were described. In this article,
      a report is presented on the first clinical case of C.hominis infection in Spain.
      It concerns a corneal ulcer caused by this recently described species. CASE
      REPORT: A 46 year-old male patient with a corneal ulcer in his left eye went to
      the Emergency Department. Specimens were obtained from the lesion, and the
      patient was admitted due to the risk of corneal perforation. The fungal culture
      of the specimens revealed a filamentous fungus that was identified by microscopic
      examination as Curvulariaspp. Using mass spectrometry (MALDI-TOF) the isolate was
      identified as Curvularia lunata. To confirm the identification, the isolate was
      sent to the National Centre of Microbiology in Spain, where ITS region sequencing
      was performed, and it was finally identified as C.hominis. The patient received
      voriconazole and progressed favourably. To repair the corneal damage, the patient
      received an amniotic membrane transplantation. CONCLUSIONS: C.hominis should be
      considered a causal agent of keratitis and sequencing techniques are now
      necessary for species-level identification of Curvularia isolates. This is the
      first case report in Spain caused by this species.

PMID- 30274955
TI  - [Clinical features and outcome in patients with mucormycosis in a tertiary
      hospital (2012-2016)].
AB  - BACKGROUND: The most common presentation of mucormycosis in the past was the
      nasosinusal involvement in patients with diabetic ketoacidosis. However, in the
      last few years, new groups of patients with risk of mucormycosis have emerged.
      AIMS AND METHODS: Retrospective analysis of the characteristics, treatment and
      evolution of patients with mucormycosis in a tertiary hospital in the years 2012
      2016. RESULTS: Of the 12 patients included in the study, 7 had a haematological
      disease as a predisposing factor, most of them (6 patients) related to
      transplantation of haematopoietic progenitors. Only one patient had diabetic
      ketoacidosis. Seven out of the twelve patients were receiving an antifungal
      treatment at the onset of symptoms, and 9 patients had received them three months
      before. The clinical presentation was rhinosinusal (16.6%), localised lung
      disease (33.3%), and musculoskeletal (25%) and disseminated disease (25%).
      Surgical debridement was performed on 8 patients. Combination therapy with
      amphotericin B and posaconazole was received by 6 patients (16% mortality), and 4
      patients were treated with amphotericin B alone (50% mortality), with an overall
      mortality of 41%. The mortality of patients with pulmonary involvement was 71%,
      increasing to 100% in the case of disseminated disease. None of the patients with
      only musculoskeletal involvement died. CONCLUSIONS: Mucormycosis has a high
      mortality rate, especially the pulmonary forms. Musculoskeletal involvement had a
      better prognosis. The main group at risk was that of patients with haematopoietic
      stem cell transplantation. Combination therapy had better results than
      monotherapy, although more experience is needed to define the most appropriate
      treatment.

PMID- 30274956
TI  - Machine learning for real-time prediction of complications in critical care: a
      retrospective study.
AB  - BACKGROUND: The large amount of clinical signals in intensive care units can
      easily overwhelm health-care personnel and can lead to treatment delays,
      suboptimal care, or clinical errors. The aim of this study was to apply deep
      machine learning methods to predict severe complications during critical care in
      real time after cardiothoracic surgery. METHODS: We used deep learning methods
      (recurrent neural networks) to predict several severe complications (mortality,
      renal failure with a need for renal replacement therapy, and postoperative
      bleeding leading to operative revision) in post cardiosurgical care in real time.
      Adult patients who underwent major open heart surgery from Jan 1, 2000, to Dec
      31, 2016, in a German tertiary care centre for cardiovascular diseases formed the
      main derivation dataset. We measured the accuracy and timeliness of the deep
      learning model's forecasts and compared predictive quality to that of established
      standard-of-care clinical reference tools (clinical rule for postoperative
      bleeding, Simplified Acute Physiology Score II for mortality, and the Kidney
      Disease: Improving Global Outcomes staging criteria for acute renal failure)
      using positive predictive value (PPV), negative predictive value, sensitivity,
      specificity, area under the curve (AUC), and the F1 measure (which computes a
      harmonic mean of sensitivity and PPV). Results were externally retrospectively
      validated with 5898 cases from the published MIMIC-III dataset. FINDINGS: Of 47
      559 intensive care admissions (corresponding to 42 007 patients), we included 11
      492 (corresponding to 9269 patients). The deep learning models yielded accurate
      predictions with the following PPV and sensitivity scores: PPV 0.90 and
      sensitivity 0.85 for mortality, 0.87 and 0.94 for renal failure, and 0.84 and
      0.74 for bleeding. The predictions significantly outperformed the standard
      clinical reference tools, improving the absolute complication prediction AUC by
      0.29 (95% CI 0.23-0.35) for bleeding, by 0.24 (0.19-0.29) for mortality, and by
      0.24 (0.13-0.35) for renal failure (p<0.0001 for all three analyses). The deep
      learning methods showed accurate predictions immediately after patient admission
      to the intensive care unit. We also observed an increase in performance in our
      validation cohort when the machine learning approach was tested against clinical
      reference tools, with absolute improvements in AUC of 0.09 (95% CI 0.03-0.15;
      p=0.0026) for bleeding, of 0.18 (0.07-0.29; p=0.0013) for mortality, and of 0.25
      (0.18-0.32; p<0.0001) for renal failure. INTERPRETATION: The observed
      improvements in prediction for all three investigated clinical outcomes have the
      potential to improve critical care. These findings are noteworthy in that they
      use routinely collected clinical data exclusively, without the need for any
      manual processing. The deep machine learning method showed AUC scores that
      significantly surpass those of clinical reference tools, especially soon after
      admission. Taken together, these properties are encouraging for prospective
      deployment in critical care settings to direct the staff's attention towards
      patients who are most at risk. FUNDING: No specific funding.

PMID- 30274957
TI  - The Importance of Male Ejaculation for Female Sexual Satisfaction and Function.
AB  - INTRODUCTION: Although links between ejaculatory control or intravaginal
      ejaculatory latency time and female sexual functioning have frequently been
      reported in the past, no study has investigated the importance of other male
      ejaculatory characteristics, such as ejaculation volume and intensity, for
      women's sexuality. AIM: To assess the importance of subjectively perceived
      ejaculation intensity and ejaculation volume for female sexual function and
      satisfaction. METHODS: This was a cross-sectional online survey including 240
      sexually active, heterosexual women (median age 27.4 years), using study-specific
      questions and validated questionnaires. MAIN OUTCOME MEASURE: Results are
      presented as means, percentages, and age-controlled partial correlation
      coefficients of the main study variables. RESULTS: 50.43% of women considered it
      very important that the partner ejaculates during intercourse. 18.3% of women
      preferred that the partner ejaculates before they reach orgasm, whereas for 53.5%
      this did not matter. 22.6% of women stated that they experienced a more intense
      orgasm when their partner ejaculated during vaginal intercourse. 17.4% reported
      that they definitely experienced a more intensive orgasm depending on the
      intensity of their partner's ejaculation, whereas for 17.8% this did not matter
      at all. 20.9% of women did not feel that their orgasm was more intense depending
      on the subjectively felt ejaculate quantity, whereas the majority (37.9%) stated
      that it did not matter. 13.1% of women regarded the quantity of expelled
      ejaculate as an expression of their own sexual attractiveness. Women stating that
      they experienced more intense orgasms when the partner ejaculated, when the
      partner experienced a more intense ejaculation, and when he expelled a greater
      ejaculate quantity also reported better lifelong orgasmic function (r = 0.24, r =
      0.15, r = .26, respectively) and more lifelong sexual satisfaction (r = .29, r =
      .15, r = 26, respectively). CLINICAL IMPLICATIONS: The perception of ejaculatory
      characteristics can be related to the female partner's sexual satisfaction and
      overall sexual functioning. STRENGTH & LIMITATIONS: This is the very first study
      to explore the importance of male ejaculation volume and intensity for women's
      sexual functioning. Data are of self-report nature and ejaculation
      characteristics were not objectively measured but by women's self-report.
      CONCLUSION: Although male ejaculation and its different aspects seem to play an
      important role for women, the study demonstrates a considerable variability of
      women's attitudes toward ejaculatory characteristics. Further research is
      required to examine the sources of this variability. Burri A, Buchmeier J, Porst
      H. The importance of male ejaculation for female sexual satisfaction and
      function. J Sex Med 2018;15:1600-1608.

PMID- 30274958
TI  - Complaint-Directed Mini-Interventions for Depressive Symptoms: A Health Economic
      Evaluation of Unguided Web-Based Self-Help Interventions Based on a Randomized
      Controlled Trial.
AB  - BACKGROUND: Depression prevention and early intervention have become a top
      priority in the Netherlands, but with considerable room for improvement. To
      address this, Web-based complaint-directed mini-interventions (CDMIs) were
      developed. These brief and low-threshold interventions focus on psychological
      stress, sleep problems, and worry, because these complaints are highly prevalent,
      are demonstrably associated with depression, and have substantial economic
      impact. OBJECTIVE: The objective of this economic evaluation was to examine the
      added value of Web-based, unguided, self-help CDMIs compared with a wait-listed
      control group with unrestricted access to usual care from both a societal and a
      health care perspective. METHODS: This health economic evaluation was embedded in
      a randomized controlled trial. The study entailed 2 arms, in which 3 Web-based
      CDMIs were compared with a no-intervention waiting-list control group (which
      received the intervention after 3 months). We conducted measurements at baseline,
      and at 3 and 6 months. The primary outcome was the rate of responders to
      treatment on depressive symptoms as measured by the Inventory of Depressive
      Symptomatology Self-Report (IDS-SR). We estimated change in quality of life by
      calculating effect sizes (Cohen d) for individual pre- and posttreatment IDS-SR
      scores using a conversion factor to map a change in standardized effect size onto
      a corresponding change in utility. We calculated incremental cost-effectiveness
      ratios using bootstraps (5000 times) of seemingly unrelated regression equations
      and constructed cost-effectiveness acceptability curves for the costs per quality
      adjusted life-year (QALY) gained. RESULTS: Of 329 study participants, we randomly
      assigned 165 to the CDMI group. At 3 months, the rate of responders to treatment
      was 13.9% (23/165) in the CDMI group and 7.3% (12/164) in the control group. At 3
      months, participants in the CDMI group gained 0.15 QALYs compared with baseline,
      whereas participants in the control group gained 0.03 QALYs. Average total costs
      per patient at 3 months were ?2094 for the CDMI group and ?2230 for the control
      group (excluding baseline costs). Bootstrapped seemingly unrelated regression
      equations models resulted in a dominant incremental cost-effectiveness ratio (ie,
      lower costs and a higher rate of responders to treatment) for the CDMI group
      compared with the control group at 3 months, with the same result for the costs
      per QALY gained. Various sensitivity analyses attested to the robustness of the
      findings of the main analysis. CONCLUSIONS: Brief and low-threshold Web-based,
      unguided, self-help CDMIs have the potential to be a cost-effective addition to
      usual care for adults with mild to moderate depressive symptoms. The CDMIs
      improved health status, while reducing participant health care costs, and hence
      dominated the care-as-usual control condition. As intervention costs were
      relatively low, and the internet is readily available in the Western world, we
      believe CDMIs can be easily implemented on a large scale. TRIAL REGISTRATION:
      Netherlands Trial Register NTR4612;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4612 (Archived by
      WebCite at http://www.webcitation.org/6n4PVYddM).

PMID- 30274959
TI  - Physician and Pharmacist Medication Decision-Making in the Time of Electronic
      Health Records: Mixed-Methods Study.
AB  - BACKGROUND: Primary care needs to be patient-centered, integrated, and
      interprofessional to help patients with complex needs manage the burden of
      medication-related problems. Considering the growing problem of polypharmacy,
      increasing attention has been paid to how and when medication-related decisions
      should be coordinated across multidisciplinary care teams. Improved knowledge on
      how integrated electronic health records (EHRs) can support interprofessional
      shared decision-making for medication therapy management is necessary to continue
      improving patient care. OBJECTIVE: The objective of our study was to examine how
      physicians and pharmacists understand and communicate patient-focused medication
      information with each other and how this knowledge can influence the design of
      EHRs. METHODS: This study is part of a broader cross-Canada study between
      patients and health care providers around how medication-related decisions are
      made and communicated. We visited community pharmacies, team-based primary care
      clinics, and independent-practice family physician clinics throughout Ontario,
      Nova Scotia, Alberta, and Quebec. Research assistants conducted semistructured
      interviews with physicians and pharmacists. A modified version of the
      Multidisciplinary Framework Method was used to analyze the data. RESULTS: We
      collected data from 19 pharmacies and 9 medical clinics and identified 6 main
      themes from 34 health care professionals. First, Interprofessional Shared
      Decision-Making was not occurring and clinicians made decisions based on their
      understanding of the patient. Physicians and pharmacists reported indirect
      Communication, incomplete Information specifically missing insight into
      indication and adherence, and misaligned Processes of Care that were further
      compounded by EHRs that are not designed to facilitate collaboration. Scope of
      Practice examined professional and workplace boundaries for pharmacists and
      physicians that were internally and externally imposed. Physicians decided on the
      degree of the Physician-Pharmacist Relationship, often predicated by colocation.
      CONCLUSIONS: We observed limited communication and collaboration between primary
      care providers and pharmacists when managing medications. Pharmacists were
      missing key information around reason for use, and physicians required accurate
      information around adherence. EHRs are a potential tool to help clinicians
      communicate information to resolve this issue. EHRs need to be designed to
      facilitate interprofessional medication management so that pharmacists and
      physicians can move beyond task-based work toward a collaborative approach.

PMID- 30274960
TI  - Health Information Discrepancies Between Internet Media and Scientific Papers
      Reporting on Omega-3 Supplement Research: Comparative Analysis.
AB  - BACKGROUND: Dietary supplements are the most used complementary and alternative
      health modality in the United States, and omega-3 supplements continue to be the
      most popularly used nonvitamin or nonmineral supplements by adults. Users of
      dietary supplements report that they obtain health guidance from internet media
      resources, but there is question as to whether or not these resources provide the
      necessary evidence to guide health decisions. Current evidence suggests that
      there is a mistranslation occurring somewhere between researchers and the media.
      OBJECTIVE: The aim of this study was to conduct a comparative cross-sectional
      analysis to identify areas of discordance created when science is translated from
      the laboratory to Web-based news media. METHODS: A Google news search provided
      our convenience sample of 40 omega-3 supplement-based media reports stratified by
      the years 2009 to 2012. Media reports (n=17) were compared with the corresponding
      scientific papers for content. Report and scientific paper content were extracted
      using commonly accepted reporting guideline domains, and domains were then
      compared for detecting underlying omissions or mistranslations in reporting. Mean
      scores for all of the scientific papers and media reports were assessed for each
      domain. RESULTS: Scientific papers (n=14) generally maintained a mean close to
      complete for each reporting domain. The only domain where there was not a
      significant difference between media and scientific reporting match was within
      the objectives domain (chi21= 0.8, P=.36). Media reports (n=17) more frequently
      reported potential caveats and warnings for consumers with a mean domain for
      caveat reporting of 0.88, with possible scores falling between 0 and 1.
      CONCLUSIONS: There are inherent differences in the intended audience, structure,
      and goals in scientific and media communications. These differences should be
      explored further, and consumers should be made aware of them. Additional
      considerations for balanced reporting and reader accessibility are also necessary
      to take into account and are explored further in this analysis.

PMID- 30274961
TI  - How Users Experience and Use an eHealth Intervention Based on Self-Regulation:
      Mixed-Methods Study.
AB  - BACKGROUND: eHealth interventions show stronger effects when informed by solid
      behavioral change theories; for example, self-regulation models supporting people
      in translating vague intentions to specific actions have shown to be effective in
      altering health behaviors. Although these theories inform developers about which
      behavioral change techniques should be included, they provide limited information
      about how these techniques can be engagingly implemented in Web-based
      interventions. Considering the high levels of attrition in eHealth, investigating
      users' experience about the implementation of behavior change techniques might be
      a fruitful avenue. OBJECTIVE: The objective of our study was to investigate how
      users experience the implementation of self-regulation techniques in a Web-based
      intervention targeting physical activity and sedentary behavior in the general
      population. METHODS: In this study, 20 adults from the general population used
      the intervention for 5 weeks. Users' website data were explored, and
      semistructured interviews with each of the users were performed. A directed
      content analysis was performed using NVivo Software. RESULTS: The techniques
      "providing feedback on performance," "action planning," and "prompting review of
      behavioral goals" were appreciated by users. However, the implementation of
      "barrier identification/problem solving" appeared to frustrate users; this was
      also reflected by the users' website data-many coping plans were of poor quality.
      Most users were well aware of the benefits of adopting a more active way of
      living and stated not to have learned novel information. However, they
      appreciated the provided information because it reminded them about the
      importance of having an active lifestyle. Furthermore, prompting users to self
      monitor their behavioral change was not sufficiently stimulating to make users
      actually monitor their behavior. CONCLUSIONS: Iteratively involving potential end
      users offers guidance to optimally adapt the implementation of various behavior
      change techniques to the target population. We recommend creating short
      interventions with a straightforward layout that support users in creating and
      evaluating specific plans for action.

PMID- 30274962
TI  - The Untapped Potential of the Gaming Community: Narrative Review.
AB  - BACKGROUND: Video gamers are a population at heightened risk of developing
      obesity due to the sedentary nature of gaming, increased energy intake, and the
      disruption caused to their sleep. This increases their risk of developing a
      number of noncommunicable diseases. To date, research seeking to improve health
      behaviors has focused on developing novel video games to promote behavior change.
      Although positive results have emerged from this research, large-scale success
      has been limited due to the lack of transferability to mainstream games and the
      focus on children and adolescents. The gaming community has a number of unique
      aspects, which have received comparatively less attention than the development of
      new video games. OBJECTIVE: The purpose of this paper is to highlight under
      researched areas that have the potential to encourage positive health behavior
      among this community. METHODS: A narrative review of the lay and academic
      literature was conducted to provide context and support to our claims that
      further research could be beneficial in this area. RESULTS: Research has found
      that advertising can have implicit effects on an individual's memories, which
      could influence later decisions. However, the effect of the exponential growth of
      in-game advertisements and the brand sponsorship of gaming events and
      professional gamers have not been explored in the gaming community. The
      possibility of using advertising techniques to encourage positive health
      behaviors within games or at these events has also not been explored. Research
      suggests that virtual communities can be effective at disseminating health
      information, but the efficacy of this needs to be explored using known community
      influencers within the gaming community. CONCLUSIONS: This paper has highlighted
      a number of potential avenues for the development of interventions within the
      gaming community. Further research must be conducted alongside game developers to
      ensure that any in-game developed interventions do not deter gameplay and gamers
      to ensure that potential approaches are acceptable.

PMID- 30274963
TI  - Web-Based Mindfulness Interventions for Mental Health Treatment: Systematic
      Review and Meta-Analysis.
AB  - BACKGROUND: Web-based mindfulness interventions are increasingly delivered
      through the internet to treat mental health conditions. OBJECTIVE: The objective
      of this study was to determine the effectiveness of web-based mindfulness
      interventions in clinical mental health populations. Secondary aims were to
      explore the impact of study variables on the effectiveness of web-based
      mindfulness interventions. METHODS: We performed a systematic review and meta
      analysis of studies investigating the effects of web-based mindfulness
      interventions on clinical populations. RESULTS: The search strategy yielded 12
      eligible studies. Web-based mindfulness interventions were effective in reducing
      depression in the total clinical sample (n=656 g=-0.609, P=.004) and in the
      anxiety disorder subgroup (n=313, g=-0.651, P<.001), but not in the depression
      disorder subgroup (n=251, P=.18). Similarly, web-based mindfulness interventions
      significantly reduced anxiety in the total clinical sample (n=756, g=-0.433,
      P=.004) and the anxiety disorder subgroup (n=413, g=-0.719, P<.001), but not in
      the depression disorder group (n=251, g=-0.213, P=.28). Finally, web-based
      mindfulness interventions improved quality of life and functioning in the total
      sample (n=591, g=0.362, P=.02) in the anxiety disorder subgroup (n=370, g=0.550,
      P=.02) and mindfulness skills in the total clinical sample (n=251, g=0.724,
      P<.001). CONCLUSIONS: Results support the effectiveness of web-based mindfulness
      interventions in reducing depression and anxiety and in enhancing quality of life
      and mindfulness skills, particularly in those with clinical anxiety. Results
      should be interpreted with caution given the high heterogeneity of web-based
      mindfulness interventions and the low number of studies included.

PMID- 30274964
TI  - Monitoring Twitter Conversations for Targeted Recruitment in Cancer Trials in Los
      Angeles County: Protocol for a Mixed-Methods Pilot Study.
AB  - BACKGROUND: Insufficient recruitment of participants remains a critical roadblock
      to successful clinical research, particularly clinical trials. Social media
      provide new ways for connecting potential participants with research
      opportunities. Researchers suggest that the social network Twitter may serve as a
      rich avenue for exploring how patients communicate about their health issues and
      increasing enrollment in cancer clinical trials. However, there is a lack of
      evidence that Twitter offers practical utility and impact. OBJECTIVE: This pilot
      study aimed to examine the feasibility and impact of using Twitter monitoring
      data (ie, user activity and their conversations about cancer-related conditions
      and concerns expressed by Twitter users in Los Angeles County) as a tool for
      enhancing clinical trial recruitment at a comprehensive cancer center. METHODS:
      We will conduct a mixed-methods interrupted time series study design with a
      before-and-after social media recruitment intervention. On the basis of a
      preliminary analysis of eligible trials, we plan to onboard at least 84 clinical
      trials across 6 disease categories: breast cancer, colon cancer, kidney cancer,
      lymphoma, non-small cell lung cancer, and prostate cancer that are open to
      accrual at the University of Southern California (USC) Norris Comprehensive
      Cancer Center. We will monitor messages about these 6 cancer conditions posted by
      Twitter users in Los Angeles County. Recruitment for the trials will occur
      through the Twitter account (@USCTrials). Primary study outcomes-feasibility and
      acceptance of the social media intervention among targeted Twitter users and the
      study teams of the onboarded trials-will be assessed using qualitative interviews
      and the 4-point Likert scale and by calculating the proportion of targeted
      Twitter users who engaged with outreach messages. Second, impact of the social
      media intervention will be measured by calculating the proportion of enrollees in
      trials. The enrollment rate will be compared between the active intervention
      period and the prior 10 months as historical control for each disease trial
      group. This study has been funded by the National Center for Advancing
      Translational Science through a Clinical and Translational Science Award. Study
      approval was obtained from the clinical investigations committee at USC Norris
      and the institutional review board at USC. RESULTS: Recruitment on Twitter
      started in February 2018. Data collection will be completed in November 2018.
      CONCLUSIONS: This pilot project will provide preliminary data and practical
      insight into the application of publicly available Twitter data to identify and
      recruit clinical trial participants across 6 cancer disease types. We will shed
      light on the acceptance of the social media intervention among Twitter users and
      study team members of the onboarded trials. If successful, the findings will
      inform a multisite randomized controlled trial to determine the efficacy of the
      social media intervention across different locations and populations. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT03408561;
      https://clinicaltrials.gov/ct2/show/NCT03408561 (Archived by WebCite at
      http://www.webcitation.org/72LihauzW). REGISTERED REPORT IDENTIFIER: RR1
      10.2196/9762.

PMID- 30274965
TI  - Early Detection of Cardiovascular Changes After Radiotherapy for Breast Cancer:
      Protocol for a European Multicenter Prospective Cohort Study (MEDIRAD EARLY HEART
      Study).
AB  - BACKGROUND: Breast cancer is the most common cancer among women, and radiotherapy
      plays a major role in its treatment. However, breast cancer radiotherapy can lead
      to incidental irradiation of the heart, resulting in an increased risk for a
      variety of heart diseases arising many years after radiotherapy. Therefore,
      identifying breast cancer patients at the highest risk for radiation-induced
      cardiac complications is crucial for developing strategies for primary and
      secondary prevention, which may contribute to healthy aging. There is still a
      need for precise knowledge on the relationship between radiation dose to specific
      cardiac structures and early subclinical cardiac changes and their occurrence
      over time that could finally lead to cardiac complications. OBJECTIVE: The
      MEDIRAD EARLY HEART study aims to identify and validate new cardiac imaging and
      circulating biomarkers of radiation-induced cardiovascular changes arising within
      first 2 years of breast cancer radiotherapy and to develop risk models
      integrating these biomarkers combined with precise dose metrics of cardiac
      structures based on three-dimensional dosimetry. METHODS: The EARLY HEART study
      is a multicenter, prospective cohort study in which 250 women treated for breast
      cancer and followed for 2 years after radiotherapy will be included. Women
      treated with radiotherapy without chemotherapy for a unilateral breast cancer and
      aged 40-75 years meet the inclusion criteria. Baseline and follow-up data include
      cardiac measurements based on two-dimensional speckle-tracking echocardiography,
      computed tomography coronary angiography, cardiac magnetic resonance imaging, and
      a wide panel of circulating biomarkers of cardiac injury. The absorbed dose will
      be evaluated globally for the heart and different substructures. Furthermore, the
      dose-response relationship will allow modeling the radiation-induced occurrence
      and evolution of subclinical cardiac lesions and biomarkers to develop prediction
      models. RESULTS: This study details the protocol of the MEDIRAD EARLY HEART study
      and presents the main limits and advantages of this international project. The
      inclusion of patients began in 2017. Preliminary results are expected to be
      published in 2019, and complete analysis should be published in 2021.
      CONCLUSIONS: The MEDIRAD EARLY HEART study will allow identifying the main
      cardiac imaging and blood-based determinants of radiation-induced cardiac
      injuries to better propose primary and secondary preventive measures in order to
      contribute to enhanced patient care and quality of life. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT03297346; https://clinicaltrials.gov/ct2/show/NCT03297346
      (Archived by WebCite at http://www.webcitation.org/72KS7MIUU). REGISTERED REPORT
      IDENTIFIER: RR1-10.2196/9906.

PMID- 30274966
TI  - A Smartphone App to Foster Power in the Everyday Management of Living With
      Schizophrenia: Qualitative Analysis of Young Adults' Perspectives.
AB  - BACKGROUND: Literature indicates that using smartphone technology is a feasible
      way of empowering young adults recently diagnosed with schizophrenia to manage
      everyday living with their illness. The perspective of young adults on this
      matter, however, is unexplored. OBJECTIVE: This study aimed at exploring how
      young adults recently diagnosed with schizophrenia used and perceived a
      smartphone app (MindFrame) as a tool to foster power in the everyday management
      of living with their illness. METHODS: Using participatory design thinking and
      methods, MindFrame was iteratively developed. MindFrame consists of a smartphone
      app that allows young adults to access resources to aid their self-management.
      The app is affiliated with a website to support collaboration with their health
      care providers (HCPs). From January to December 2016, community-dwelling young
      adults with a recent diagnosis of schizophrenia were invited to use MindFrame as
      part of their care. They customized the resources while assessing their health on
      a daily basis. Then, they were invited to evaluate the use and provide their
      perspective on the app. The evaluation was qualitative, and data were generated
      from in-depth interviews. Data were analyzed using a hermeneutical approach.
      RESULTS: A total of 98 individuals were eligible for the study (mean age 24.8,
      range 18-36). Of these, 27 used MindFrame and 13 participated in the evaluation.
      The analysis showed that to the young adults, MindFrame served to foster power in
      their everyday management of living with schizophrenia. When MindFrame was used
      with the HCPs consistently for more than a month, it could provide them with the
      power to keep up their medication, to keep a step ahead of their illness, and to
      get appropriate help based on their needs. This empowered them to stay on track
      with their illness, thus in control of it. It was also reported that MindFrame
      could fuel the fear of restraint and illness exacerbation, thereby disempowering
      some from feeling certain and secure. CONCLUSIONS: The findings demonstrate that
      young adults diagnosed with schizophrenia are amenable to use a smartphone app to
      monitor their health, manage their medication, and stay alert of the early signs
      of illness exacerbation. This may empower them to stay on track with their
      illness, thus in control of it. This indicates the potential of smartphone-based
      care being capable of aiding this specific population to more confidently manage
      their new life situation. The potentially disempowering aspect of MindFrame
      accentuates a need for further research to understand the best uptake and the
      limitations of smartphone-based schizophrenia care of young adults.

PMID- 30274968
TI  - Twitter-Based Influenza Detection After Flu Peak via Tweets With Indirect
      Information: Text Mining Study.
AB  - BACKGROUND: The recent rise in popularity and scale of social networking services
      (SNSs) has resulted in an increasing need for SNS-based information extraction
      systems. A popular application of SNS data is health surveillance for predicting
      an outbreak of epidemics by detecting diseases from text messages posted on SNS
      platforms. Such applications share the following logic: they incorporate SNS
      users as social sensors. These social sensor-based approaches also share a common
      problem: SNS-based surveillance are much more reliable if sufficient numbers of
      users are active, and small or inactive populations produce inconsistent results.
      OBJECTIVE: This study proposes a novel approach to estimate the trend of patient
      numbers using indirect information covering both urban areas and rural areas
      within the posts. METHODS: We presented a TRAP model by embedding both direct
      information and indirect information. A collection of tweets spanning 3 years (7
      million influenza-related tweets in Japanese) was used to evaluate the model.
      Both direct information and indirect information that mention other places were
      used. As indirect information is less reliable (too noisy or too old) than direct
      information, the indirect information data were not used directly and were
      considered as inhibiting direct information. For example, when indirect
      information appeared often, it was considered as signifying that everyone already
      had a known disease, leading to a small amount of direct information. RESULTS:
      The estimation performance of our approach was evaluated using the correlation
      coefficient between the number of influenza cases as the gold standard values and
      the estimated values by the proposed models. The results revealed that the
      baseline model (BASELINE+NLP) shows .36 and that the proposed model (TRAP+NLP)
      improved the accuracy (.70, +.34 points). CONCLUSIONS: The proposed approach by
      which the indirect information inhibits direct information exhibited improved
      estimation performance not only in rural cities but also in urban cities, which
      demonstrated the effectiveness of the proposed method consisting of a TRAP model
      and natural language processing (NLP) classification.

PMID- 30274967
TI  - Emergency Physician Use of the Alberta Netcare Portal, a Province-Wide
      Interoperable Electronic Health Record: Multi-Method Observational Study.
AB  - BACKGROUND: The adoption and use of an electronic health record (EHR) can
      facilitate real-time access to key health information and support improved
      outcomes. Many Canadian provinces use interoperable EHRs (iEHRs) to facilitate
      health information exchange, but the clinical use and utility of iEHRs has not
      been well described. OBJECTIVE: The aim of this study was to describe the use of
      a provincial iEHR known as the Alberta Netcare Portal (ANP) in 4 urban Alberta
      emergency departments. The secondary objectives were to characterize the time
      spent using the respective electronic tools and identify the aspects that were
      perceived as most useful by emergency department physicians. METHODS: In this
      study, we have included 4 emergency departments, 2 using paper-based ordering
      (University of Alberta Hospital [UAH] and Grey Nuns Community Hospital [GNCH])
      and 2 using a commercial vendor clinical information system (Peter Lougheed
      Centre [PLC] and Foothills Medical Centre [FMC]). Structured clinical
      observations of ANP use and system audit logs analysis were compared at the 4
      sites from October 2014 to March 2016. RESULTS: Observers followed 142 physicians
      for a total of 566 hours over 376 occasions. The median percentage of observed
      time spent using ANP was 8.5% at UAH (interquartile range, IQR, 3.7%-13.3%), 4.4%
      at GNCH (IQR 2.4%-4.4%), 4.6% at FMC (IQR 2.4%-7.6%), and 5.1% at PLC (IQR 3.0%
      7.7%). By combining administrative and access audit data, the median number of
      ANP screens (ie, results and reports displayed on a screen) accessed per patient
      visit were 20 at UAH (IQR 6-67), 9 at GNCH (IQR 4-29), 7 at FMC (IQR 2-18), and 5
      at PLC (IQR 2-14). When compared with the structured clinical observations, the
      statistical analysis of screen access data showed that ANP was used more at UAH
      than the other sites. CONCLUSIONS: This study shows that the iEHR is well
      utilized at the 4 sites studied, and the usage patterns implied clinical value.
      Use of the ANP was highest in a paper-based academic center and lower in the
      centers using a commercial emergency department clinical information system. More
      study about the clinical impacts of using iEHRs in the Canadian context including
      longer term impacts on quality of practice and safety are required.

PMID- 30274969
TI  - Social Media Users' Perception of Telemedicine and mHealth in China: Exploratory
      Study.
AB  - BACKGROUND: The use of telemedicine and mHealth has increased rapidly in the
      People's Republic of China. While telemedicine and mHealth have great potential,
      wide adoption of this technology depends on how patients, health care providers,
      and other stakeholders in the Chinese health sector perceive and accept the
      technology. OBJECTIVE: To explore this issue, we aimed to examine a social media
      platform with a dedicated focus on health information technology and informatics
      in China. Our goal is to utilize the findings to support further research.
      METHODS: In this exploratory study, we selected a social media platform-HC3i.cn
      to examine the perception of telemedicine and mHealth in China. We performed
      keyword analysis and analyzed the prevalence and term frequency-inverse document
      frequency of keywords in the selected social media platform; furthermore, we
      performed qualitative analysis. RESULTS: We organized the most prominent 16
      keywords from 571 threads into 8 themes: (1) Question versus Answer; (2) Hospital
      versus Clinic; (3) Market versus Company; (4) Doctor versus Nurse; (5) Family
      versus Patient; (6) iPad versus Tablet; (7) System versus App; and (8) Security
      versus Caregiving. Social media participants perceived not only significant
      opportunities associated with telemedicine and mHealth but also barriers to
      overcome to realize these opportunities. CONCLUSIONS: We identified interesting
      issues in this paper by studying a social media platform in China. Among other
      things, participants in the selected platform raised concerns about quality and
      costs associated with the provision of telemedicine and mHealth, despite the new
      technology's great potential to address different issues in the Chinese health
      sector. The methods applied in this paper have some limitations, and the findings
      may not be generalizable. We have discussed directions for further research.

PMID- 30274970
TI  - Is palliative care cost-effective in low-income and middle-income countries? A
      mixed-methods systematic review.
AB  - INTRODUCTION: Of the 40 million people globally in need of palliative care (PC),
      just 14% receive it, predominantly in high-income countries. Within fragile
      health systems that lack PC, incurable illness is often marked by pain and
      suffering, as well as burdensome costs. In high-income settings, PC decreases
      healthcare utilisation, thus enhancing value. Similar cost-effectiveness models
      are lacking in low-income and middle-income countries and with them, the impetus
      and funding to expand PC delivery. METHODS: We conducted a systematic search of
      seven databases to gather evidence of the cost-effectiveness of PC in low-income
      and middle-income countries. We extracted and synthesised palliative outcomes and
      economic data from original research studies occurring in low-income and middle
      income countries. This review adheres to Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses guidelines and includes a quality appraisal. RESULTS:
      Our search identified 10 eligible papers that included palliative and economic
      outcomes in low-income and middle-income countries. Four provided true cost
      effectiveness analyses in comparing the costs of PC versus alternative care, with
      PC offering cost savings, favourable palliative outcomes and positive patient
      reported and family-reported outcomes. CONCLUSIONS: Despite the small number of
      included studies, wide variety of study types and lack of high-quality studies,
      several patterns emerged: (1) low-cost PC delivery in low-income and middle
      income countries is possible, (2) patient-reported outcomes are favourable and
      (3) PC is less costly than the alternative. This review highlights the
      extraordinary need for robust cost-effectiveness analysis of PC in low-income and
      middle-income countries in order to develop health economic models for the
      delivery of PC, direct resource allocation and guide healthcare policy for PC
      delivery in low-income and middle-income countries.

PMID- 30274971
TI  - Intravenous methadone in a patient with advanced cancer.
AB  - A patient receiving maintenance treatment with methadone (MTM) was treated with
      parenteral methadone for intense pain crises in cancer of the tongue with severe
      mucositis and dysphagia. Authors like Manfredi et al describe good results in the
      use of methadone as an analgesic in patients with MTM. The difficulties which
      arise with parenteral use derive from the drug itself and from those to whom the
      treatment is administered: serious side effects like malignant arrhythmias and
      respiratory depression and the complex nature of these patients, addicted to
      opiates with a terminal illness and pain which is difficult to treat. It should
      be administered by experts in palliative care in a healthcare unit where it can
      be successfully monitored.

PMID- 30274974
TI  - US had record flu deaths last year, says CDC.

PMID- 30274975
TI  - Who will the Defence and National Rehabilitation Centre rehabilitate?

PMID- 30274973
TI  - High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early
      Onset Pancreatic Cancer.
AB  - Introduction: We aimed to determine the prevalence and landscape of germline
      mutations among patients with young-onset pancreatic ductal adenocarcinoma (PDAC)
      as well as their influence in prognosis.Methods: Patients from two cohorts were
      studied, the high-risk cohort (HRC), which included 584 PDAC patients who
      received genetic counseling at The University of Texas MD Anderson Cancer Center,
      and a general cohort (GC) with 233 metastatic PDAC patients. We defined germline
      DNA sequencing on 13 known pancreatic cancer susceptibility genes. The prevalence
      and landscape of mutations were determined, and clinical characteristics
      including survival were analyzed.Results: A total of 409 patients underwent
      genetic testing (277 from HRC and 132 from GC). As expected, the HRC had higher
      prevalence of germline mutations compared with the GC: 17.3% versus 6.81%. The
      most common mutations in both cohorts were in BRCA1/2 and mismatch-repair (MMR)
      genes. Patients younger than 60 years old had significantly higher prevalence of
      germline mutations in both the HRC [odds ratios (OR), 1.93 +/- 1.03-3.70, P =
      0.039] and GC (4.78 +/- 1.10-32.95, P = 0.036). Furthermore, PDAC patients with
      germline mutations in the GC had better overall survival than patients without
      mutations (HR, 0.44; 95% CI of HR, 0.25-0.76, P = 0.030).Discussion: Germline
      mutations are highly prevalent in patients with PDAC of early onset and can be
      predictive of better outcomes. Considering emerging screening strategies for
      relatives carrying susceptibility genes as well as impact on therapy choices,
      genetic counseling and testing should be encouraged in PDAC patients,
      particularly those of young onset. Cancer Prev Res; 11(11); 679-86. (c)2018 AACR.

PMID- 30274976
TI  - Denaturation-Enhanced Droplet Digital PCR for Liquid Biopsies.
AB  - BACKGROUND: Although interest in droplet-digital PCR technology (ddPCR) for cell
      free circulating DNA (cfDNA) analysis is burgeoning, the technology is
      compromised by subsampling errors and the few clinical targets that can be
      analyzed from limited input DNA. The paucity of starting material acts as a
      "glass ceiling" in liquid biopsies because, irrespective how analytically
      sensitive ddPCR techniques are, detection limits cannot be improved past DNA
      input limitations. METHODS: We applied denaturation-enhanced ddPCR (dddPCR) using
      fragmented genomic DNA (gDNA) with defined mutations. We then tested dddPCR on
      cfDNA from volunteers and patients with cancer for commonly-used mutations. gDNA
      and cfDNA were tested with and without end repair before denaturation and digital
      PCR. RESULTS: By applying complete denaturation of double-stranded DNA before
      ddPCR droplet formation the number of positive droplets increased. dddPCR using
      gDNA resulted in a 1.9-2.0-fold increase in data-positive droplets, whereas
      dddPCR applied on highly-fragmented cfDNA resulted in a 1.6-1.7-fold increase.
      End repair of cfDNA before denaturation enabled cfDNA to display a 1.9-2.0-fold
      increase in data-positive signals, similar to gDNA. Doubling of data-positive
      droplets doubled the number of potential ddPCR assays that could be conducted
      from a given DNA input and improved ddPCR precision for cfDNA mutation detection.
      CONCLUSIONS: dddPCR is a simple and useful modification in ddPCR that enables
      extraction of more information from low-input clinical samples with minor change
      in protocols. It should be applicable to all ddPCR platforms for mutation
      detection and, potentially, for gene copy-number analysis in cancer and prenatal
      screening.

PMID- 30274972
TI  - TET2 Deficiency Causes Germinal Center Hyperplasia, Impairs Plasma Cell
      Differentiation, and Promotes B-cell Lymphomagenesis.
AB  - : TET2 somatic mutations occur in ~10% of diffuse large B-cell lymphomas (DLBCL)
      but are of unknown significance. Herein, we show that TET2 is required for the
      humoral immune response and is a DLBCL tumor suppressor. TET2 loss of function
      disrupts transit of B cells through germinal centers (GC), causing GC
      hyperplasia, impaired class switch recombination, blockade of plasma cell
      differentiation, and a preneoplastic phenotype. TET2 loss was linked to focal
      loss of enhancer hydroxymethylation and transcriptional repression of genes that
      mediate GC exit, such as PRDM1. Notably, these enhancers and genes are also
      repressed in CREBBP-mutant DLBCLs. Accordingly, TET2 mutation in patients yields
      a CREBBP-mutant gene-expression signature, CREBBP and TET2 mutations are
      generally mutually exclusive, and hydroxymethylation loss caused by TET2
      deficiency impairs enhancer H3K27 acetylation. Hence, TET2 plays a critical role
      in the GC reaction, and its loss of function results in lymphomagenesis through
      failure to activate genes linked to GC exit signals. SIGNIFICANCE: We show that
      TET2 is required for exit of the GC, B-cell differentiation, and is a tumor
      suppressor for mature B cells. Loss of TET2 phenocopies CREBBP somatic mutation.
      These results advocate for sequencing TET2 in patients with lymphoma and for the
      testing of epigenetic therapies to treat these tumors.See related commentary by
      Shingleton and Dave, p. 1515.This article is highlighted in the In This Issue
      feature, p. 1494.

PMID- 30274978
TI  - Direct to Consumer Fitness DNA Testing.

PMID- 30274979
TI  - Doctors' wellbeing: learning from the past can help improve the future.

PMID- 30274977
TI  - Redesigning Prostate Cancer Screening Strategies to Reduce Overdiagnosis.

PMID- 30274980
TI  - Copenhagen Prospective Personalized Oncology (CoPPO) - Clinical utility of using
      molecular profiling to select patients to phase 1 trials.
AB  - PURPOSE: We evaluated the clinical benefit of tumor molecular profiling (MP) to
      select treatment in the phase 1 setting. EXPERIMENTAL DESIGN: Patients with
      advanced solid cancers and exhausted treatment options referred to a phase 1 unit
      were included in a prospective single-centre single-arm open-label study
      (NCT02290522). Tumor biopsies were obtained for comprehensive genomic analysis
      including whole exome sequencing (WES) and RNA sequencing. When possible,
      patients were treated with regimen matched to the genomic profile. Primary
      endpoint was progression free survival. RESULTS: From May 2013 to January 2017 a
      total of 591 patients were enrolled with 500 patients undergoing biopsy. Genomic
      profiles were obtained in 460 patients and a potential actionable target was
      identified in 352 (70%) of 500 biopsied patients. One hundred and one patients
      (20%) received matched treatment based on either gene mutations or RNA expression
      levels of targets available in early clinical trials or off-label treatment.
      Objective response according to RECIST1.1 was observed in 15/101 patients (0% CR,
      15% PR) with a median PFS of 12 weeks (95% CI 9.9-14.4). CONCLUSIONS: Our study
      supports the feasibility of genomic profiling to select patients in the phase 1
      setting and suggests that genomic matching can be beneficial for a minor subset
      of patients with no other treatment options. Randomized studies may validate this
      assumption.

PMID- 30274981
TI  - The Role of Angiogenesis in Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) accounts for about 90% of all primary liver
      cancers and is the second leading cause of cancer-related deaths worldwide. The
      hypervascular nature of most HCC tumors underlines the importance of angiogenesis
      in the pathobiology of these tumors. Several angiogenic pathways have been
      identified as being dysregulated in HCC, suggesting they may be involved in the
      development and pathogenesis of HCC. These data provide practical targets for
      systemic treatments such as those targeting the vascular endothelial growth
      factor receptor and its ligand. However, the clinical relevance of other more
      recently identified angiogenic pathways in HCC pathogenesis or treatment remains
      unclear. Research into molecular profiles and validation of prognostic or
      predictive biomarkers will be required to identify the patient subsets most
      likely to experience meaningful benefit from this important class of agents. Clin
      Cancer Res; 1-9. (c)2018 AACR.

PMID- 30274983
TI  - Extended Adjuvant Therapy with Neratinib Plus Fulvestrant Blocks ER/HER2
      Crosstalk and Maintains Complete Responses of ER+/HER2+ Breast Cancers:
      Implications to the ExteNET Trial.
AB  - Purpose: The phase III ExteNET trial showed improved invasive disease-free
      survival in patients with HER2+ breast cancer treated with neratinib versus
      placebo after trastuzumab-based adjuvant therapy. The benefit from neratinib
      appeared to be greater in patients with ER+/HER2+ tumors. We thus sought to
      discover mechanisms that may explain the benefit from extended adjuvant therapy
      with neratinib.Experimental Design: Mice with established ER+/HER2+ MDA-MB-361
      tumors were treated with paclitaxel plus trastuzumab +/- pertuzumab for 4 weeks,
      and then randomized to fulvestrant +/- neratinib treatment. The benefit from
      neratinib was evaluated by performing gene expression analysis for 196 ER
      targets, ER transcriptional reporter assays, and cell-cycle analyses.Results:
      Mice receiving "extended adjuvant" therapy with fulvestrant/neratinib maintained
      a complete response, whereas those treated with fulvestrant relapsed rapidly. In
      three ER+/HER2+ cell lines (MDA-MB-361, BT-474, UACC-893) but not in ER+/HER2-
      MCF7 cells, treatment with neratinib induced ER reporter transcriptional
      activity, whereas treatment with fulvestrant resulted in increased HER2 and EGFR
      phosphorylation, suggesting compensatory reciprocal crosstalk between the ER and
      ERBB RTK pathways. ER transcriptional reporter assays, gene expression, and
      immunoblot analyses showed that treatment with neratinib/fulvestrant, but not
      fulvestrant, potently inhibited growth and downregulated ER reporter activity, P
      AKT, P-ERK, and cyclin D1 levels. Finally, similar to neratinib, genetic and
      pharmacologic inactivation of cyclin D1 enhanced fulvestrant action against
      ER+/HER2+ breast cancer cells.Conclusions: These data suggest that ER blockade
      leads to reactivation of ERBB RTKs and thus extended ERBB blockade is necessary
      to achieve durable clinical outcomes in patients with ER+/HER2+ breast cancer.
      Clin Cancer Res; 1-13. (c)2018 AACR.

PMID- 30274982
TI  - Proteogenomic Characterization of Patient-Derived Xenografts Highlights the Role
      of REST in Neuroendocrine Differentiation of Castration-Resistant Prostate
      Cancer.
AB  - Background: An increasing number of castration-resistant prostate cancer (CRPC)
      tumors exhibit neuroendocrine (NE) features. NE prostate cancer (NEPC) has poor
      prognosis, and its development is poorly understood.Experimental Design: We
      applied mass spectrometry-based proteomics to a unique set of 17 prostate cancer
      patient-derived xenografts (PDX) to characterize the effects of castration in
      vivo, and the proteome differences between NEPC and prostate adenocarcinomas.
      Genome-wide profiling of REST-occupied regions in prostate cancer cells was
      correlated to the expression changes in vivo to investigate the role of the
      transcriptional repressor REST in castration-induced NEPC
      differentiation.Results: An average of 4,881 proteins were identified and
      quantified from each PDX. Proteins related to neurogenesis, cell-cycle
      regulation, and DNA repair were found upregulated and elevated in NEPC, while the
      reduced levels of proteins involved in mitochondrial functions suggested a
      prevalent glycolytic metabolism of NEPC tumors. Integration of the REST chromatin
      bound regions with expression changes indicated a direct role of REST in
      regulating neuronal gene expression in prostate cancer cells. Mechanistically,
      depletion of REST led to cell-cycle arrest in G1, which could be rescued by p53
      knockdown. Finally, the expression of the REST-regulated gene secretagogin (SCGN)
      correlated with an increased risk of suffering disease relapse after radical
      prostatectomy.Conclusions: This study presents the first deep characterization of
      the proteome of NEPC and suggests that concomitant inhibition of REST and the p53
      pathway would promote NEPC. We also identify SCGN as a novel prognostic marker in
      prostate cancer. Clin Cancer Res; 1-14. (c)2018 AACR.

PMID- 30274984
TI  - Targeting Resistance against the MDM2 Inhibitor RG7388 in Glioblastoma Cells by
      the MEK Inhibitor Trametinib.
AB  - Purpose: Resistance is an obstacle of glioma therapy. Despite targeted
      interventions, tumors harbor primary resistance or become resistant over short
      course of treatment. This study examined the mouse double minute 2 (MDM2)
      inhibitor RG7388 together with radiotherapy and analyzed strategies to overcome
      acquired MDM2 inhibitor resistance in glioblastoma.Experimental Design: Effects
      of RG7388 and radiotherapy were analyzed in p53 wild-type glioblastoma cell lines
      and glioma-initiating cells. RG7388 resistant cells were generated by increasing
      RG7388 doses over 3 months. Regulated pathways were investigated by microarray,
      qRT-PCR, and immunoblot analysis and specifically inhibited to evaluate rational
      salvage therapies at RG7388 resistance. Effects of RG7388 and trametinib
      treatment were challenged in an orthotopical mouse model with RG7388 resistant
      U87MG glioblastoma cells.Results: MDM2 inhibition required functional p53 and
      showed synergistic activity with radiotherapy in first-line treatment. Long-term
      exposure to RG7388 induced resistance by activation of the extracellular signal
      regulated kinases 1/2 (ERK1/2)-insulin growth factor binding protein 1 (IGFBP1)
      signaling cascade, which was specifically overcome by ERK1/2 pathway inhibition
      with trametinib and knockdown of IGFBP1. Combining trametinib with continued
      RG7388 treatment enhanced antitumor effects at RG7388 resistance in vitro and in
      vivo Conclusions: These data provide a rationale for combining RG7388 and
      radiotherapy as first-line therapy with a specific relevance for tumors
      insensitive to alkylating standard chemotherapy and for the addition of
      trametinib to continued RG7388 treatment as salvage therapy after acquired
      resistance against RG7388 for clinical practice. Clin Cancer Res; 1-13. (c)2018
      AACR.

PMID- 30274985
TI  - Robust Activity of Avapritinib, Potent and Highly Selective Inhibitor of Mutated
      KIT, in Patient-derived Xenograft Models of Gastrointestinal Stromal Tumors.
AB  - Purpose: Gastrointestinal stromal tumors (GIST) are commonly treated with
      tyrosine kinase inhibitors (TKI). The majority of patients with advanced GIST
      ultimately become resistant to TKI due to acquisition of secondary KIT mutations,
      whereas primary resistance is mainly caused by PDGFRA p.D842V mutation. We tested
      the activity of avapritinib, a potent and highly selective inhibitor of mutated
      KIT and PDGFRA, in three patient-derived xenograft (PDX) GIST models carrying
      different KIT mutations, with differential sensitivity to standard
      TKI.Experimental Design: NMRI nu/nu mice (n = 93) were transplanted with human
      GIST xenografts with KIT exon 11+17 (UZLX-GIST9 KIT 11+17 ), exon 11 (UZLX-GIST3
      KIT 11 ), or exon 9 (UZLX-GIST2B KIT9 ) mutations, respectively. We compared
      avapritinib (10 and 30 mg/kg/once daily) versus vehicle, imatinib (50 mg/kg/bid)
      or regorafenib (30 mg/kg/once daily; UZLX-GIST9 KIT11+17 ); avapritinib (10, 30,
      100 mg/kg/once daily) versus vehicle or imatinib [UZLX-GIST3 KIT11 ]; and
      avapritinib (10, 30, 60 mg/kg/once daily) versus vehicle, imatinib (50, 100
      mg/kg/twice daily), or sunitinib (40 mg/kg/once daily; UZLX-GIST2B KIT9
      ).Results: In all models, avapritinib resulted in reduction of tumor volume,
      significant inhibition of proliferation, and reduced KIT signaling. In two
      models, avapritinib led to remarkable histologic responses, increase in
      apoptosis, and inhibition of MAPK-phosphorylation. Avapritinib showed superior
      (UZLX-GIST9 KIT 11+17 and -GIST2B KIT 9 ) or equal (UZLX-GIST3 KIT 11 ) antitumor
      activity to the standard dose of imatinib. In UZLX-GIST9 KIT 11+17 , the
      antitumor effects of avapritinib were significantly better than with imatinib or
      regorafenib.Conclusions: Avapritinib has significant antitumor activity in GIST
      PDX models characterized by different KIT mutations and sensitivity to
      established TKI. These data provide strong support for the ongoing clinical
      trials with avapritinib in patients with GIST (NCT02508532, NCT03465722). Clin
      Cancer Res; 1-10. (c)2018 AACR.

PMID- 30274987
TI  - Static stability predicts the continuum of interleg coordination patterns in
      Drosophila.
AB  - During walking, insects must coordinate the movements of their six legs for
      efficient locomotion. This interleg coordination is speed dependent: fast walking
      in insects is associated with tripod coordination patterns, whereas slow walking
      is associated with more variable, tetrapod-like patterns. To date, however, there
      has been no comprehensive explanation as to why these speed-dependent shifts in
      interleg coordination should occur in insects. Tripod coordination would be
      sufficient at low walking speeds. The fact that insects use a different interleg
      coordination pattern at lower speeds suggests that it is more optimal or
      advantageous at these speeds. Furthermore, previous studies focused on discrete
      tripod and tetrapod coordination patterns. Experimental data, however, suggest
      that changes observed in interleg coordination are part of a speed-dependent
      spectrum. Here, we explore these issues in relation to static stability as an
      important aspect for interleg coordination in Drosophila We created a model that
      uses basic experimentally measured parameters in fruit flies to find the interleg
      phase relationships that maximize stability for a given walking speed. The model
      predicted a continuum of interleg coordination patterns spanning the complete
      range of walking speeds as well as an anteriorly directed swing phase
      progression. Furthermore, for low walking speeds, the model predicted tetrapod
      like patterns to be most stable, whereas at high walking speeds, tripod
      coordination emerged as most optimal. Finally, we validated the basic assumption
      of a continuum of interleg coordination patterns in a large set of experimental
      data from walking fruit flies and compared these data with the model-based
      predictions.

PMID- 30274986
TI  - Outcomes of idiopathic chronic large pericardial effusion.
AB  - OBJECTIVE: Aim of this paper is to evaluate the outcomes of 'idiopathic' chronic
      large pericardial effusions without initial evidence of pericarditis. METHODS:
      All consecutive cases of idiopathic chronic large pericardial effusions evaluated
      from 2000 to 2015 in three Italian tertiary referral centres for pericardial
      diseases were enrolled in a prospective cohort study. The term 'idiopathic' was
      applied to cases that performed a complete diagnostic evaluation to exclude a
      specific aetiology. A clinical and echocardiographic follow-up was performed
      every 3-6 months. RESULTS: 100 patients were included (mean age 61.3+/-14.6
      years, 54 females, 44 patients were asymptomatic according to clinical
      evaluation) with a mean follow-up of 50 months. The baseline median size of the
      effusion (evaluated as the largest end-diastolic echo-free space) was 25 mm (IQR
      8) and decreased to a mean value of 7 mm (IQR 19; p<0.0001) with complete
      regression in 39 patients at the end of follow-up. There were no new aetiological
      diagnoses. Adverse events were respectively: cardiac tamponade in 8 patients
      (8.0%), pericardiocentesis in 30 patients (30.0%), pericardial window in 12 cases
      (12.0%) and pericardiectomy in 3 patients (3.0%). Recurrence-free survival and
      complications-free survival was better in patients treated without interventions
      (log rank p=0.0038). CONCLUSIONS: The evolution of 'idiopathic' chronic large
      pericardial effusions is usually benign with reduction of the size of the
      effusion in the majority of cases, and regression in about 40% of cases. The risk
      of cardiac tamponade is 2.2%/year and recurrence/complications survival was
      better in patients treated conservatively without interventions.

PMID- 30274989
TI  - Replicability of Introgression Under Linked, Polygenic Selection.
AB  - We study how a block of genome with a large number of weakly selected loci
      introgresses under directional selection into a genetically homogeneous
      population. We derive exact expressions for the expected rate of growth of any
      fragment of the introduced block during the initial phase of introgression, and
      show that the growth rate of a single-locus variant is largely insensitive to its
      own additive effect, but depends instead on the combined effect of all loci
      within a characteristic linkage scale. The expected growth rate of a fragment is
      highly correlated with its long-term introgression probability in populations of
      moderate size, and can hence identify variants that are likely to introgress
      across replicate populations. We clarify how the introgression probability of an
      individual variant is determined by the interplay between hitchhiking with
      relatively large fragments during the early phase of introgression and selection
      on fine-scale variation within these, which at longer times results in
      differential introgression probabilities for beneficial and deleterious loci
      within successful fragments. By simulating individuals, we also investigate how
      introgression probabilities at individual loci depend on the variance of fitness
      effects, the net fitness of the introduced block, and the size of the recipient
      population, and how this shapes the net advance under selection. Our work
      suggests that even highly replicable substitutions may be associated with a range
      of selective effects, which makes it challenging to fine map the causal loci that
      underlie polygenic adaptation.

PMID- 30274988
TI  - BMP Signaling Determines Body Size via Transcriptional Regulation of Collagen
      Genes in Caenorhabditis elegans.
AB  - Body size is a tightly regulated phenotype in metazoans that depends on both
      intrinsic and extrinsic factors. While signaling pathways are known to control
      organ and body size, the downstream effectors that mediate their effects remain
      poorly understood. In the nematode Caenorhabditis elegans, a Bone Morphogenetic
      Protein (BMP)-related signaling pathway is the major regulator of growth and body
      size. We investigated the transcriptional network through which the BMP pathway
      regulates body size and identified cuticle collagen genes as major effectors of
      growth control. We demonstrate that cuticle collagens can act as positive
      regulators (col-41), negative regulators (col-141), or dose-sensitive regulators
      (rol-6) of body size. Moreover, we find a requirement of BMP signaling for stage
      specific expression of cuticle collagen genes. We show that the Smad signal
      transducers directly bind conserved Smad-binding elements in regulatory regions
      of col-141 and col-142, but not of col-41 Hence, cuticle collagen genes may be
      directly and indirectly regulated via the BMP pathway. Our work thus connects a
      conserved signaling pathway with its critical downstream effectors, advancing
      insight into how body size is specified. Since collagen mutations and
      misregulation are implicated in numerous human genetic disorders and injury
      sequelae, understanding how collagen gene expression is regulated has broad
      implications.

PMID- 30274990
TI  - Kidneys on Chips: Emerging Technology for Preclinical Drug Development.

PMID- 30274991
TI  - A perioperative approach to the opioid crisis.

PMID- 30274992
TI  - Influence of socioeconomic events on cause-specific mortality in urban Shanghai,
      China, from 1974 to 2015: a population-based longitudinal study.
AB  - BACKGROUND: Understanding how socioeconomic events influence cause-specific
      mortality is essential for optimizing disease-control strategies. We
      characterized long-term trends in cause-specific mortality in a stable population
      from a very large urban centre. METHODS: We derived population data from 1974 to
      2015 on vital status, demographics and causes of death from the death
      registration system in Yangpu District, Shanghai, China. We examined temporal
      trends in mortality and assessed the effects of age, period and birth cohort.
      RESULTS: Over 41 879 864 person-years of follow-up, we analyzed 290 332 deaths:
      3.80% from communicable conditions (group 1), 86.50% from noncommunicable
      diseases (group 2), and 5.56% from injuries (group 3). Age-standardized mortality
      decreased after 1988 for group 1 (average annual percentage change [AAPC] -6.7,
      95% confidence interval [CI] -9.3 to -4.1), after 1995 for group 2 (AAPC -2.9,
      95% CI -3.5 to -2.3), and after 1994 for group 3 (AAPC -5.4, 95% CI -6.3 to 
      4.5), after improvements in public health and clinical service infrastructure and
      the removal of polluting industries during the 1980s. We observed increased
      mortality from group 2 and group 3 causes in those born between 1955 and 1965, a
      period that included the Great Chinese Famine. Cause-specific mortality risks
      increased in those born after 1949 for cancer and diabetes only. INTERPRETATION:
      Birth cohorts exposed to extreme starvation in early life had increased premature
      cause-specific mortality in later life. Decreased cause-specific mortality
      followed improvements in public health, medical infrastructure and pollution
      control, but not for cancer or diabetes, likely because of exposure to new risk
      factors.

PMID- 30274993
TI  - Improving the quality of health care in Canada.

PMID- 30274994
TI  - Progressive renal failure complicated by transient and recurrent ureteral
      obstruction.

PMID- 30274995
TI  - Chronic pulmonary aspergillosis after pulmonary tuberculosis.

PMID- 30274996
TI  - To what end, evolutionary medicine?

PMID- 30274998
TI  - How many doctors do we actually need?

PMID- 30274997
TI  - Focus on saving money lets patients and surgeons down.

PMID- 30274999
TI  - Medical students protest steadily rising tuition fees.

PMID- 30275000
TI  - Closing male-female gaps in clinical care requires addressing entrenched ideas on
      gender risks.

PMID- 30275001
TI  - Combination of exome sequencing and immune testing confirms Aicardi-Goutieres
      syndrome type 5 in a challenging pediatric neurology case.
AB  - Exome sequencing is increasingly being used to help diagnose pediatric neurology
      cases when clinical presentations are not specific. However, interpretation of
      equivocal results that include variants of uncertain significance remains a
      challenge. In those cases, follow-up testing and clinical correlation can help
      clarify the clinical relevance of the molecular findings. In this report, we
      describe the diagnostic odyssey of a 4-year-old girl who presented with global
      developmental delay and seizures, with leukodystrophy seen on MRI. Clinical
      evaluation, MRI, and comprehensive metabolic testing were performed, followed by
      whole-exome sequencing (WES), parental testing, follow-up testing, and
      retrospective detailed clinical evaluation. WES identified two candidate
      causative pathogenic variants in SAMHD1, a gene associated with the recessive
      condition Aicardi-Goutieres syndrome (AGS) type 5 (OMIM 612952): a previously
      reported pathogenic variant NM_015474 c.602T>A (p.I201N), maternally inherited,
      and a rare missense variant of uncertain significance, c.1293A>T(p.L431F).
      Analysis of type I interferon-related biomarkers demonstrated that the patient
      has an interferon signature characteristic of AGS. Retrospective detailed
      clinical evaluation showed that the girl has a phenotype consistent with AGS5, a
      rare neurological condition. These results further define the phenotypic spectrum
      associated with specific SAMHD1 variants, including heterozygous variants in AGS
      carriers, and support the idea that autoinflammatory dysregulation is part of the
      disease pathophysiology. More broadly, this work highlights the issues and
      methodology involved in ascribing clinical relevance to interpretation of
      variants detected by WES.

PMID- 30275002
TI  - Multimodal molecular analysis of an atypical small cell carcinoma of the ovary,
      hypercalcemic type.
AB  - A 12-yr-old normocalcemic female treated for a ruptured ovarian juvenile
      granulosa cell tumor at an outside hospital presented for exploratory laparotomy
      and gross surgical debulking of pelvic recurrence. Morphologically, the tumor was
      composed of sheets and nests of small blue cells forming cysts of various sizes
      and focal mucinous differentiation. Epithelial membrane antigen (EMA), patchy
      inhibin, and strong and diffuse p53 immunoreactivity were also observed. A
      revised diagnosis of mixed sex cord stromal tumor with heterologous elements was
      favored because of the inhibin immunoreactivity. Targeted next-generation
      sequencing of the tumor revealed a SMARCA4 c.1141C>T, p.Arg381Ter
      (NM_001128849.1) nonsense mutation and an in-frame 18-bp TP53 deletion
      (c.594_611del18, p.Gly199_Glu204del, NM_001126112.2). Cytogenetic analysis
      revealed a normal 46,XX karyotype, and OncoScan single-nucleotide polymorphism
      array analysis demonstrated copy-neutral loss of heterozygosity (CN-LOH) of
      19p13.3-19p13.2 and mosaic CN-LOH of 17p13.3-p11.2 encompassing the SMARCA4 and
      TP53 loci, respectively. Subsequent germline SMARCA4 sequencing confirmed a
      heterozygous SMARCA4 p.Arg381Ter mutation. In lieu of the molecular findings, the
      diagnosis was amended to small cell carcinoma of the ovary, hypercalcemic type
      (SCCOHT). The patient was treated aggressively with paclitaxel, carboplatin, and
      bevacizumab. She received an autologous stem cell transplant but died 5 mo after
      SCCOHT diagnosis secondary to complications of the transplant. This case expands
      the morphologic, immunophenotypic, and genomic spectrum of SCCOHT and highlights
      how multimodal molecular analysis can assist with the diagnosis and clinical
      management of SCCOHT patients.

PMID- 30275003
TI  - Whole-exome sequencing enables correct diagnosis and surgical management of rare
      inherited childhood anemia.
AB  - Correct diagnosis of inherited bone marrow failure syndromes is a challenge
      because of the significant overlap in clinical presentation of these disorders.
      Establishing right genetic diagnosis is crucial for patients' optimal clinical
      management and family counseling. A nondysmorphic infant reported here developed
      severe transfusion-dependent anemia and met clinical criteria for diagnosis of
      Diamond-Blackfan anemia (DBA). However, whole-exome sequencing demonstrated that
      the child was a compound heterozygote for a paternally inherited pathogenic
      truncating variant (SPTA1 c.4975 C>T) and a novel maternally inherited missense
      variant of uncertain significance (SPTA1 c.5029 G>A) within the spectrin gene,
      consistent with hereditary hemolytic anemia due to disruption of red blood cell
      (RBC) cytoskeleton. Ektacytometry demonstrated abnormal membrane flexibility of
      the child's RBCs. Scanning electron microscopy revealed morphological aberrations
      of the patient's RBCs. Both parents were found to have mild hereditary
      elliptocytosis. Importantly, patients with severe RBC membrane defects may be
      successfully managed with splenectomy to minimize peripheral destruction of
      misshapen RBCs, whereas patients with DBA require lifelong transfusions, steroid
      therapy, or hematopoietic stem cell transplantation. As suggested by the WES
      findings, splenectomy rendered our patient transfusion-independent, improving the
      family's quality of life and preventing transfusion-related iron overload. This
      case illustrates the utility of whole-exome sequencing in clinical care of
      children with genetic disorders of unclear presentation.

PMID- 30275004
TI  - Biallelic variants in VARS in a family with two siblings with intellectual
      disability and microcephaly: case report and review of the literature.
AB  - Two male siblings ages 15 and 10 yr old had similar features of intellectual
      disability, developmental delay, severe speech impairment, microcephaly,
      prematurity, and transient elevation of liver enzymes in infancy. Exome
      sequencing revealed one novel (c.65C>A; p.Ala22Asp) and one ultra-rare
      (c.3214T>C; p.Phe1072Leu) predicted damaging missense variant in trans in the
      gene encoding cytoplasmic valyl-tRNA synthetase (VARS). Biallelic variants in
      VARS have previously been associated with a neurodevelopmental disorder
      characterized by microcephaly, seizures, and cortical atrophy (NDMSCA; MIM
      #617802). Although our patients have no history of seizures or cortical atrophy,
      we suggest that the biallelic variants in VARS p.Ala22Asp and p.Phe1072Leu in
      this family are likely pathogenic and associated with NDMSCA, expanding the
      clinical phenotype of the condition.

PMID- 30275005
TI  - Rapid communication of efforts to resolve differences or update variant
      interpretations in ClinVar through case-level data sharing.

PMID- 30275006
TI  - Risk of psychiatric disorders in overactive bladder syndrome: a nationwide cohort
      study in Taiwan.
AB  - Population-based cohort study investigating the risk of depression and other
      psychiatric disorders for patients with overactive bladder (OAB) syndrome is
      unavailable. This study investigated the subsequent risk of psychiatric disorders
      among patients with OAB in an Asian population. Using data from the National
      Health Insurance Research Database of Taiwan, we established a cohort with 811
      patients in an exposed group with OAB between January 1, 2000 and December 31,
      2000, and a non-exposed group, without OAB, of 2433 patients without OAB matched
      by age and year of diagnosis. The occurrence of psychiatric disorders and Cox
      regression model measured adjusted HRs (aHR) were monitored until the end of
      2013. The overall incidence of psychiatric disorders was 41.7% higher in the
      exposed group with OAB than in the non-exposed group without OAB (14.2% vs 10.1%,
      p<0.001), with an aHR of 1.34 (95% CI 1.12 to 1.80, p<0.001) for the OAB cohort.
      OAB was associated with the increased risk of dementia, anxiety, depressive,
      sleep, and psychotic disorders, with aHRs as 1.53 (p=0.040), 1.61 (p<0.001), 2.10
      (p<0.001), 1.43 (p<0.001), and 2.49 (p=0.002), respectively. The risk of
      psychiatric disorders, including depression and anxiety, is significantly higher
      in patients with OAB than in those without OAB. Evaluation of psychiatric status
      in patients with OAB is strongly recommended.

PMID- 30275007
TI  - KDM6B overexpression activates innate immune signaling and impairs hematopoiesis
      in mice.
AB  - KDM6B is an epigenetic regulator that mediates transcriptional activation during
      differentiation, including in bone marrow (BM) hematopoietic stem and progenitor
      cells (HSPCs). Overexpression of KDM6B has been reported in BM HSPCs of patients
      with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML).
      Whether the overexpression of KDM6B contributes to the pathogenesis of these
      diseases remains to be elucidated. To study this, we generated a Vav-KDM6B mouse
      model, which overexpresses KDM6B in the hematopoietic compartment. KDM6B
      overexpression alone led to mild hematopoietic phenotype, and chronic innate
      immune stimulation of Vav-KDM6B mice with the Toll-like receptor (TLR) ligand
      lipopolysaccharide (LPS) resulted in significant hematopoietic defects. These
      defects recapitulated features of MDS and CMML, including leukopenia, dysplasia,
      and compromised repopulating function of BM HSPCs. Transcriptome studies
      indicated that KDM6B overexpression alone could lead to activation of disease
      relevant genes such as S100a9 in BM HSPCs, and when combined with innate immune
      stimulation, KDM6B overexpression resulted in more profound overexpression of
      innate immune and disease-relevant genes, indicating that KDM6B was involved in
      the activation of innate immune signaling in BM HSPCs. Finally, pharmacologic
      inhibition of KDM6B with the small molecule inhibitor GSK-J4 ameliorated the
      ineffective hematopoiesis observed in Vav-KDM6B mice. This effect was also
      observed when GSK-J4 was applied to the primary BM HSPCs of patients with MDS by
      improving their repopulating function. These results indicate that overexpression
      of KDM6B mediates activation of innate immune signals and has a role in MDS and
      CMML pathogenesis, and that KDM6B targeting has therapeutic potential in these
      myeloid disorders.

PMID- 30275008
TI  - Tracking Anti-Staphylococcus aureus Antibodies Produced In Vivo and Ex Vivo
      during Foot Salvage Therapy for Diabetic Foot Infections Reveals Prognostic
      Insights and Evidence of Diversified Humoral Immunity.
AB  - Management of foot salvage therapy (FST) for diabetic foot infections (DFI) is
      challenging due to the absence of reliable diagnostics to identify the etiologic
      agent and prognostics to justify aggressive treatments. As Staphylococcus aureus
      is the most common pathogen associated with DFI, we aimed to develop a multiplex
      immunoassay of IgG in serum and medium enriched for newly synthesized anti-S.
      aureus antibodies (MENSA) generated from cultured peripheral blood mononuclear
      cells of DFI patients undergoing FST. Wound samples were collected from 26 DFI
      patients to identify the infecting bacterial species via 16S rRNA sequencing.
      Blood was obtained over 12 weeks of FST to assess anti-S. aureus IgG levels in
      sera and MENSA. The results showed that 17 out of 26 infections were
      polymicrobial and 12 were positive for S. aureus While antibody titers in serum
      and MENSA displayed similar diagnostic potentials to detect S. aureus infection,
      MENSA showed a 2-fold-greater signal-to-background ratio. Multivariate analyses
      revealed increases in predictive power of diagnosing S. aureus infections (area
      under the receiver operating characteristic curve [AUC] > 0.85) only when
      combining titers against different classes of antigens, suggesting cross
      functional antigenic diversity. Anti-S. aureus IgG levels in MENSA decreased with
      successful FST and rose with reinfection. In contrast, IgG levels in serum
      remained unchanged throughout the 12-week FST. Collectively, these results
      demonstrate the applicability of serum and MENSA for diagnosis of S. aureus DFI
      with increased power by combining functionally distinct titers. We also found
      that tracking MENSA has prognostic potential to guide clinical decisions during
      FST.

PMID- 30275009
TI  - Cross Talk between MarR-Like Transcription Factors Coordinates the Regulation of
      Motility in Uropathogenic Escherichia coli.
AB  - The MarR-like protein PapX represses the transcription of the flagellar master
      regulator genes flhDC in uropathogenic Escherichia coli (UPEC), the primary cause
      of uncomplicated urinary tract infections (UTIs). PapX is encoded by the pap
      operon, which also encodes the adherence factors termed P fimbriae. Both
      adherence and motility are critical for productive colonization of the urinary
      tract. However, the mechanisms involved in coordinating the transition between
      adherence and motility are not well characterized. UPEC strain CFT073 carries
      both papX and a homolog, focX, located in the foc operon encoding F1C fimbriae.
      In this study, we characterized the dose effects of "X" genes on flagellar gene
      expression and cross talk between focX and papX We found that both FocX and PapX
      repress flhD transcription. However, we determined that the DeltapapX mutant was
      hypermotile, while the loss of focX did not affect motility. We further
      investigated this phenotype and found that FocX functions as a repressor of papX
      Additionally, we identified a proximal independent promoter upstream of both focX
      and papX and assessed the expression of focX and papX during culture in human
      urine and on LB agar plates compared to LB medium. Finally, we characterized the
      contributions of PapX and FocX to fitness in the ascending murine model of UTI
      and observed a subtle, but not statistically significant, fitness defect in
      colonization of the kidneys. Altogether, these results expand our understanding
      of the impact of carrying multiple X genes on the coordinated regulation of
      motility and adherence in UPEC.

PMID- 30275011
TI  - Polymorphisms in receptors involved in opsonic and non-opsonic phagocytosis and
      the risk of infection in oncohematological patients.
AB  - High-risk hematologic malignancies are a privileged setting for infection by
      opportunistic microbes, invasive mycoses being one of the most serious
      complications. Recently, the genetic background has emerged as an unanticipated
      risk factor. For this reason, polymorphisms for genes encoding archetypal
      receptors involved in the opsonic and non-opsonic clearance of microbes,
      pentraxin-3, and Dectin-1, respectively, were studied and correlated with the
      risk of infection. Fungal, bacterial, and viral infections were registered in a
      group of 198 patients with high-risk hematologic malignancies. Polymorphisms for
      pentraxin-3 gene (PTX3) showed a significant association with the risk of fungal
      infection by Candida spp and, especially, by Aspergillus spp. This link remained
      even in patients undergoing antifungal prophylaxis, thus demonstrating the
      clinical relevance of PTX3 in the defense against fungi. CLEC7A polymorphisms did
      not show any definite correlation with the risk of invasive mycosis nor did they
      influence the expression of Dectin-1 isoforms generated by alternative splicing.
      PTX3 mRNA expression was significantly lower in samples from healthy volunteers
      who showed the polymorphisms, although not differences were observed in the
      extent of the induction elicited by bacterial lipopolysaccharide and heat-killed
      C. albicans, thus suggesting that the expression of PTX3 at the start of
      infection may influence the clinical outcome. PTX3 mRNA expression can be a good
      biomarker to establish proper antifungal prophylaxis in immunodepressed patients.

PMID- 30275010
TI  - Deletion of Interleukin-4 Receptor Alpha-Responsive Keratinocytes in BALB/c Mice
      Does Not Alter Susceptibility to Cutaneous Leishmaniasis.
AB  - The skin microenvironment at the site of infection plays a role in the early
      events that determine protective T helper 1/type 1 immune responses during
      cutaneous leishmaniasis (CL) infection. During CL in nonhealing BALB/c mice,
      early interleukin-4 (IL-4) can instruct dendritic cells for protective Th1
      immunity. Additionally, keratinocytes, which are the principal cell type in the
      skin epidermis, have been shown to secrete IL-4 early after Leishmania major
      infection. Here, we investigated whether IL-4/IL-13 signaling via the common IL-4
      receptor alpha chain (IL-4Ralpha) on keratinocytes contributes to susceptibility
      during experimental CL. To address this, keratinocyte-specific IL-4Ralpha
      deficient (KRT14cre IL-4Ralpha-/lox) mice on a BALB/c genetic background were
      generated by gene targeting and site-specific recombination (Cre/loxP) under the
      control of the keratinocyte-specific krt14 locus. Following high-dose infection
      with L. major IL-81 and LV39 promastigotes subcutaneously in the footpad, footpad
      swelling, parasite burden, IFN-gamma/IL-4/IL-13 cytokine production, and type 1
      and type 2 antibody responses were similar between KRT14cre IL-4Ralpha-/lox and
      littermate control IL-4Ralpha-/lox BALB/c mice. An intradermal infection with low
      dose L. major IL-81 and LV39 promastigotes in the ear showed results in infected
      KRT14cre IL-4Ralpha-/lox BALB/c mice similar to those of littermate control IL
      4Ralpha-/lox BALB/c mice, with the exception of a significant decrease observed
      in parasite burden only at the site of LV39 infection in the ear. Collectively,
      our results show that autocrine and paracrine signaling of IL-4/IL-13 through the
      IL-4Ralpha chain on keratinocytes does not influence the establishment of a
      nonhealing Th2 immune response in BALB/c mice during L. major infection.

PMID- 30275012
TI  - The S-layer protein of a Clostridium difficile SLCT-11 strain displays a complex
      glycan required for normal cell growth and morphology.
AB  - Clostridium difficile is a bacterial pathogen that causes major health challenges
      worldwide. It has a well-characterized surface (S)-layer, a para-crystalline
      proteinaceous layer surrounding the cell wall. In many bacterial and archaeal
      species, the S-layer is glycosylated, but no such modifications have been
      demonstrated in C. difficile. Here, we show that a C. difficile strain of S-layer
      cassette type 11, Ox247, has a complex glycan attached via an O-linkage to Thr-38
      of the S-layer low-molecular-weight subunit. Using MS and NMR, we fully
      characterized this glycan. We present evidence that it is composed of three
      domains: (i) a core peptide-linked tetrasaccharide with the sequence -4-alpha-Rha
      3-alpha-Rha-3-alpha-Rha-3-beta-Gal-peptide; (ii) a repeating pentasaccharide with
      the sequence -4-beta-Rha-4-alpha-Glc-3-beta-Rha-4-(alpha-Rib-3-)beta-Rha-; and
      (iii) a nonreducing end-terminal 2,3 cyclophosphoryl-rhamnose attached to a
      ribose-branched sub-terminal rhamnose residue. The Ox247 genome contains a 24-kb
      locus containing genes for synthesis and protein attachment of this glycan.
      Mutations in genes within this locus altered or completely abrogated formation of
      this glycan, and their phenotypes suggested that this S-layer modification may
      affect sporulation, cell length, and biofilm formation of C. difficile In
      summary, our findings indicate that the S-layer protein of SLCT-11 strains
      displays a complex glycan and suggest that this glycan is required for C.
      difficile sporulation and control of cell shape, a discovery with implications
      for the development of antimicrobials targeting the S-layer.

PMID- 30275013
TI  - Synergistic effects of functionally distinct substitutions in beta-lactamase
      variants shed light on the evolution of bacterial drug resistance.
AB  - The CTX-M beta-lactamases have emerged as the most widespread extended-spectrum
      beta-lactamases (ESBLs) in Gram-negative bacteria. These enzymes rapidly
      hydrolyze cefotaxime, but not the related cephalosporin, ceftazidime. ESBL
      variants have evolved, however, that provide enhanced ceftazidime resistance. We
      show here that a natural variant at a nonactive site, i.e. second-shell residue
      N106S, enhances enzyme stability but reduces catalytic efficiency for cefotaxime
      and ceftazidime and decreases resistance levels. However, when the N106S variant
      was combined with an active-site variant, D240G, that enhances enzyme catalytic
      efficiency, but decreases stability, the resultant double mutant exhibited higher
      resistance levels than predicted on the basis of the phenotypes of each variant.
      We found that this epistasis is due to compensatory effects, whereby increased
      stability provided by N106S overrides its cost of decreased catalytic activity. X
      ray structures of the variant enzymes in complex with cefotaxime revealed
      conformational changes in the active-site loop spanning residues 103-106 that
      were caused by the N106S substitution and relieve steric strain to stabilize the
      enzyme, but also alter contacts with cefotaxime and thereby reduce catalytic
      activity. We noted that the 103-106 loop conformation in the N106S-containing
      variants is different from that of WT CTX-M but nearly identical to that of the
      non-ESBL, TEM-1 beta-lactamase, having a serine at the 106 position. Therefore,
      residue 106 may serve as a "switch" that toggles the conformations of the 103-106
      loop. When it is serine, the loop is in the non-ESBL, TEM-like conformation, and
      when it is asparagine, the loop is in a CTX-M-like, cefotaximase-favorable
      conformation.

PMID- 30275016
TI  - Structural attributes of mammalian prion infectivity: Insights from studies with
      synthetic prions.
AB  - Prion diseases are neurodegenerative disorders that affect many mammalian
      species. Mammalian prion proteins (PrPs) can misfold into many different
      aggregates. However, only a small subpopulation of these structures is
      infectious. One of the major unresolved questions in prion research is
      identifying which specific structural features of these misfolded protein
      aggregates are important for prion infectivity in vivo Previously, two types of
      proteinase K-resistant, self-propagating aggregates were generated from the
      recombinant mouse prion protein in the presence of identical cofactors. Although
      these two aggregates appear biochemically very similar, they have dramatically
      different biological properties, with one of them being highly infectious and the
      other one lacking any infectivity. Here, we used several MS-based structural
      methods, including hydrogen-deuterium exchange and hydroxyl radical footprinting,
      to gain insight into the nature of structural differences between these two PrP
      aggregate types. Our experiments revealed a number of specific differences in the
      structure of infectious and noninfectious aggregates, both at the level of the
      polypeptide backbone and quaternary packing arrangement. In particular, we
      observed that a high degree of order and stability of beta-sheet structure within
      the entire region between residues ~89 and 227 is a primary attribute of
      infectious PrP aggregates examined in this study. By contrast, noninfectious PrP
      aggregates are characterized by markedly less ordered structure up to residue
      ~167. The structural constraints reported here should facilitate development of
      experimentally based high-resolution structural models of infectiosus mammalian
      prions.

PMID- 30275015
TI  - Codon usage regulates human KRAS expression at both transcriptional and
      translational levels.
AB  - KRAS and HRAS are highly homologous oncogenic Ras GTPase family members that are
      mutated in a wide spectrum of human cancers. Despite having high amino acid
      identity, KRAS and HRAS have very different codon usage biases: the HRAS gene
      contains many common codons, and KRAS is enriched for rare codons. Rare codons in
      KRAS suppress its protein expression, which has been shown to affect both normal
      and cancer biology in mammals. Here, using HRAS or KRAS expression in different
      human cell lines and in vitro transcription and translation assays, we show that
      KRAS rare codons inhibit both translation efficiency and transcription and that
      the contribution of these two processes varies among different cell lines. We
      observed that codon usage regulates mRNA translation efficiency such that WT KRAS
      mRNA is poorly translated. On the other hand, common codons increased
      transcriptional rates by promoting activating histone modifications and
      recruitment of transcriptional coactivators. Finally, we found that codon usage
      also influences KRAS protein conformation, likely because of its effect on co
      translational protein folding. Together, our results reveal that codon usage has
      multidimensional effects on protein expression, ranging from effects on
      transcription to protein folding in human cells.

PMID- 30275014
TI  - The N-peptide-binding mode is critical to Munc18-1 function in synaptic
      exocytosis.
AB  - Sec1/Munc18 (SM) proteins promote intracellular vesicle fusion by binding to N
      ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). A key
      SNARE-binding mode of SM proteins involves the N-terminal peptide (N-peptide)
      motif of syntaxin, a SNARE subunit localized to the target membrane. In in vitro
      membrane fusion assays, inhibition of N-peptide motif binding previously has been
      shown to abrogate the stimulatory function of Munc18-1, a SM protein involved in
      synaptic exocytosis in neurons. The physiological role of the N-peptide-binding
      mode, however, remains unclear. In this work, we addressed this key question
      using a "clogged" Munc18-1 protein, in which an ectopic copy of the syntaxin N
      peptide motif was directly fused to Munc18-1. We found that the ectopic N-peptide
      motif blocks the N-peptide-binding pocket of Munc18-1, preventing the latter from
      binding to the native N-peptide motif on syntaxin-1. In a reconstituted system,
      we observed that clogged Munc18-1 is defective in promoting SNARE zippering. When
      introduced into induced neuronal cells (iN cells) derived from human pluripotent
      stem cells, clogged Munc18-1 failed to mediate synaptic exocytosis. As a result,
      both spontaneous and evoked synaptic transmission was abolished. These genetic
      findings provide direct evidence for the crucial role of the N-peptide-binding
      mode of Munc18-1 in synaptic exocytosis. We suggest that clogged SM proteins will
      also be instrumental in defining the physiological roles of the N-peptide-binding
      mode in other vesicle-fusion pathways.

PMID- 30275017
TI  - Ligand binding and heterodimerization with retinoid X receptor alpha (RXRalpha)
      induce farnesoid X receptor (FXR) conformational changes affecting coactivator
      binding.
AB  - Nuclear receptor farnesoid X receptor (FXR) functions as the major bile acid
      sensor coordinating cholesterol metabolism, lipid homeostasis, and absorption of
      dietary fats and vitamins. Because of its central role in metabolism, FXR
      represents an important drug target to manage metabolic and other diseases, such
      as primary biliary cirrhosis and nonalcoholic steatohepatitis. FXR and nuclear
      receptor retinoid X receptor alpha (RXRalpha) form a heterodimer that controls
      the expression of numerous downstream genes. To date, the structural basis and
      functional consequences of the FXR/RXR heterodimer interaction have remained
      unclear. Herein, we present the crystal structures of the heterodimeric complex
      formed between the ligand-binding domains of human FXR and RXRalpha. We show that
      both FXR and RXR bind to the transcriptional coregulator steroid receptor
      coactivator 1 with higher affinity when they are part of the heterodimer complex
      than when they are in their respective monomeric states. Furthermore, structural
      comparisons of the FXR/RXRalpha heterodimers and the FXR monomers bound with
      different ligands indicated that both heterodimerization and ligand binding
      induce conformational changes in the C terminus of helix 11 in FXR that affect
      the stability of the coactivator binding surface and the coactivator binding in
      FXR. In summary, our findings shed light on the allosteric signal transduction in
      the FXR/RXR heterodimer, which may be utilized for future drug development
      targeting FXR.

PMID- 30275020
TI  - Innervation of the Tumor Microenvironment-Letter.

PMID- 30275018
TI  - AKT and AMP-activated protein kinase regulate TBC1D1 through phosphorylation and
      its interaction with the cytosolic tail of insulin-regulated aminopeptidase IRAP.
AB  - In skeletal muscle, the Rab GTPase-activating (GAP) protein TBC1D1 is
      phosphorylated by AKT and AMP-activated protein kinase (AMPK) in response to
      insulin and muscle contraction. Genetic ablation of Tbc1d1 or mutation of
      distinct phosphorylation sites impairs intracellular GLUT4 retention and GLUT4
      traffic, presumably through alterations of the activation state of downstream Rab
      GTPases. Previous studies have focused on characterizing the C-terminal GAP
      domain of TBC1D1 that lacks the known phosphorylation sites, as well as putative
      regulatory domains. As a result, it has been unclear how phosphorylation of
      TBC1D1 would regulate its activity. In the present study, we have expressed,
      purified, and characterized recombinant full-length TBC1D1 in Sf9 insect cells
      via the baculovirus system. Full-length TBC1D1 showed RabGAP activity toward
      GLUT4-associated Rab8a, Rab10, and Rab14, indicating similar substrate
      specificity as the truncated GAP domain. However, the catalytic activity of the
      full-length TBC1D1 was markedly higher than that of the GAP domain. Although in
      vitro phosphorylation of TBC1D1 by AKT or AMPK increased 14-3-3 binding, it did
      not alter the intrinsic RabGAP activity. However, we found that TBC1D1 interacts
      through its N-terminal PTB domains with the cytoplasmic domain of the insulin
      regulated aminopeptidase, a resident protein of GLUT4 storage vesicles, and this
      binding is disrupted by phosphorylation of TBC1D1 by AKT or AMPK. In summary, our
      findings suggest that other regions outside the GAP domain may contribute to the
      catalytic activity of TBC1D1. Moreover, our data indicate that recruitment of
      TBC1D1 to GLUT4-containing vesicles and not its GAP activity is regulated by
      insulin and contraction-mediated phosphorylation.

PMID- 30275021
TI  - DRESS syndrome due to vemurafenib treatment: switching BRAF inhibitor to solve a
      big problem.
AB  - We present a case report of an early-onset drug reaction with eosinophilia and
      systemic symptoms (DRESS syndrome) induced by vemurafenib (BRAF inhibitor) in a
      middle-age man affected by a metastatic, BRAF mutant melanoma who was started on
      first-line metastatic treatment with vemurafenib and cobimetinib.After initiating
      the treatment, the patient presented an extensive cutaneous rash with
      eosinophilia and renal impairment. Due the constellation of signs and symptoms, a
      diagnosis of DRESS syndrome was made which strongly contraindicated the
      reintroduction of vemurafenib due to its hypersensibility reaction. Thus,
      vemurafenib was stopped immediately, and we started corticoid treatment with
      clinical improvement.Due to the contraindication to start vemurafenib again,
      after multidisciplinary view of the case and having balanced the risks and
      benefits, we successfully performed a switch to another BRAF inhibitor in a
      progressively ascending pattern, without any skin toxicity and with a good
      response of the metastatic melanoma.

PMID- 30275022
TI  - Hypoxic hepatitis and furosemide.
AB  - Hypoxic hepatitis is a rather common complication of heart, circulatory or
      respiratory failure. We present the case of a patient with hypoxic hepatitis in
      the setting of heart failure and dehydration from furosemide as a reminder of an
      important clinical lesson. The pathogenesis of hypoxia (especially in the case of
      heart failure) is explained by a two-hit mechanism in which the liver at risk of
      hypoxic injury by passive hepatic congestion (right heart failure) is
      subsequently exposed to systemic hypoperfusion, which leads to a marked and
      transient elevation of aminotransferases. In the case presented, the use of
      furosemide (at least partially) promoted the second hit because it helped to
      generate hypotension and splanchnic hypovolaemia and favoured hepatic hypoxia.

PMID- 30275023
TI  - Use of long saphenous vein graft in acute on chronic mesenteric ischaemia.
AB  - Acute mesenteric ischaemia is a relatively rare surgical emergency, but despite
      advances in diagnostic tests, the mortality of this condition remains stubbornly
      high (50%-80%). This is principally because of the non-specific nature of the
      presenting symptoms and subsequent delay in diagnosis. We report an unusual case
      of acute mesenteric ischaemia treated by emergency laparotomy, small bowel
      resection and revascularisation using reversed long saphenous vein graft.

PMID- 30275024
TI  - A delayed diagnosis: recurrent fever and beta thalassaemia.
AB  - Familial Mediterranean fever and beta-thalassaemia are two genetic disorders,
      with a largely common geographical distribution. However, they have not much else
      in common, as the first is an autoinflammatory disorder, while the other is a
      haemoglobinopathy. We describe a patient with known beta-thalassaemia intermedia
      who presented with recurrent fevers and he was diagnosed with familial
      Mediterranean fever 2 years later. We discuss whether there is an association
      between the two disorders and the cognitive biases that lead to the delay in the
      diagnosis of familial Mediterranean fever.

PMID- 30275019
TI  - Reinstating plasticity and memory in a tauopathy mouse model with an
      acetyltransferase activator.
AB  - Chromatin acetylation, a critical regulator of synaptic plasticity and memory
      processes, is thought to be altered in neurodegenerative diseases. Here, we
      demonstrate that spatial memory and plasticity (LTD, dendritic spine formation)
      deficits can be restored in a mouse model of tauopathy following treatment with
      CSP-TTK21, a small-molecule activator of CBP/p300 histone acetyltransferases
      (HAT). At the transcriptional level, CSP-TTK21 re-established half of the
      hippocampal transcriptome in learning mice, likely through increased expression
      of neuronal activity genes and memory enhancers. At the epigenomic level, the
      hippocampus of tauopathic mice showed a significant decrease in H2B but not H3K27
      acetylation levels, both marks co-localizing at TSS and CBP enhancers.
      Importantly, CSP-TTK21 treatment increased H2B acetylation levels at decreased
      peaks, CBP enhancers, and TSS, including genes associated with plasticity and
      neuronal functions, overall providing a 95% rescue of the H2B acetylome in
      tauopathic mice. This study is the first to provide in vivo proof-of-concept
      evidence that CBP/p300 HAT activation efficiently reverses epigenetic,
      transcriptional, synaptic plasticity, and behavioral deficits associated with
      Alzheimer's disease lesions in mice.

PMID- 30275025
TI  - Giant left breast hamartoma in a 45-year-old woman.
AB  - This is a case of a woman in her fifth decade of life who presented with a lump
      in her left breast. The patient underwent extensive breast investigations which
      did not confirm one particular diagnosis. The lesion was excised, and
      histological findings confirmed the diagnosis of a giant breast hamartoma. This
      case is interesting due to the largeness. As well as this, giant breast
      hamartomas are uncommon, and this case highlights the difficulty in their
      diagnosis and frequent misdiagnoses, potentially contributing to their reported
      low incidence rates. Diagnosis is difficult due to the complex appearance of the
      mass on imaging, raising the possibility of malignancy. Core biopsy is
      unremarkable, with the final diagnosis only possible on histological examination
      of the resected mass.

PMID- 30275026
TI  - Primary undifferentiated pleomorphic cardiac sarcoma with MDM2 amplification
      presenting as acute left-sided heart failure.
AB  - Primary cardiac tumours are a rare clinical entity that can present with myriad
      of non-specific cardiopulmonary symptoms. We describe a case of a 61-year-old
      previously healthy woman who presented with progressive dyspnoea and lower
      extremity swelling, suggestive of acute left-sided heart failure. Transthoracic
      echocardiogram revealed a large, 3.7*3.2 cm intracardiac mass resulting in severe
      mitral valvular dysfunction. The patient underwent surgical resection of the
      mass, however, negative margins were not obtained, and the tumour quickly
      returned. Histological and molecular analysis was consistent with the diagnosis
      of undifferentiated pleomorphic sarcoma with murine double minute 2 (MDM2)
      amplification. Given the overall grim prognosis, the patient chose to pursue
      comfort-based care. She died at home 9 months after the initial diagnosis. Here,
      we provide an updated review of the literature for the classification of
      undifferentiated pleomorphic cardiac sarcoma and potential treatment modalities.

PMID- 30275027
TI  - Primary amenorrhoea and clitoromegaly in a nulliparous woman: successful medical
      and surgical management.
AB  - Clitoromegaly is an important sign of virilisation and poses difficulty in sex
      determination, when present since birth. The diagnosis and treatment in an adult
      is a major challenge to the treating gynaecologist. The primary reason for its
      development is androgen excess due to congenital adrenal hyperplasia, polycystic
      ovarian syndrome, ovarian virilising tumours, neurofibromas, adrenal neoplasm and
      prolonged intake of anabolic steroids. A case of young nulliparous married woman
      who presented with primary amenorrhoea and clitoromegaly and was managed
      successfully has been reported.

PMID- 30275028
TI  - Imaging features of toxic megacolon.

PMID- 30275029
TI  - Red colour venous flow in the suprasternal view: a red flag sign.

PMID- 30275030
TI  - Modified laparoscopic Janeway gastrostomy: a novel adjunct for the management of
      choledocholithiasis in Roux-en-Y patients.
AB  - A 76-year-old woman with surgical history of Roux-en-Y gastric bypass presented
      with recurrent choledocholithiasis. Double balloon enteroscopy was unsuccessful
      in cannulating the biliary tree, thus, requiring surgically assisted endoscopic
      retrograde cholangiopancreaticogram (ERCP) access. Due to her stable clinical
      status, the non-urgent indication and multiple anticipated ERCPs for definitive
      biliary clearance, a more durable port of access to the ampulla was desired. A
      modified laparoscopic Janeway gastrostomy of the gastric remnant was performed
      and served as access for multiple subsequent endoscopic procedures with
      successful clearance of the biliary tree.

PMID- 30275031
TI  - Overall Approach to Trauma in the Emergency Department.

PMID- 30275032
TI  - Human and Animal Bites.
AB  - In the United States, nearly 56% of households owned a pet in 2011 according to
      the 2012 U.S. Pet Ownership & Demographics Sourcebook by the American Veterinary
      Medical Association. The survey also reports that approximately 70 million dogs
      and 74 million cats lived in households in the United States during the same
      year. (1)Human and animal bites are a frequent cause of primary care and
      emergency department visits for children. It is estimated that 250,000 human
      bites, 400,000 cat bites, and 4.5 million dog bites occur in the United States
      each year in both adults and children. (2) In the United States, approximately
      10% of all human bites will become infected in a child with a bite wound. The
      infection rate of dog bites in children is 20%. Cat bite infection rates in
      children vary but can be up to 50%. Each type of bite wound has a predisposition
      for sex and/or age. Infected bite wounds manifest with swelling, erythema, and
      tenderness with or without drainage of the affected site and can lead to serious
      complications. Most animal bite wounds are polymicrobial in nature. Pasteurella
      species (spp.) is the most common organism isolated from both cat and dog bites.
      The microbiology of human bites consists of both aerobic and anaerobic
      bacteria.Basic medical management of bite wounds includes thorough cleansing and
      debridement. Irrigation, closure, and need to obtain culture depend on the type
      of bite wound, the appearance of the wound, the and timing of medical evaluation
      after the initial injury. Amoxicillin-clavulanate is the antibiotic of choice for
      prophylaxis and empirical therapy for children who are not allergic to
      penicillin. With most animal bites being preventable injuries, healthcare
      providers caring for children have an important role discussing pet safety with
      the child and the family.

PMID- 30275033
TI  - Collagen Vascular Diseases: SLE, Dermatomyositis, Scleroderma, and MCTD.

PMID- 30275034
TI  - Case 1: 14-month-old Boy with Refusal to Bear Weight.

PMID- 30275035
TI  - Case 2: Headaches with Recurrent Rash and Mucosal Ulcerations.

PMID- 30275036
TI  - Case 3: A 10-year-old Boy with Saber Shins.

PMID- 30275037
TI  - Case 4: Unexplained Fever in a 5-month-old Boy.

PMID- 30275038
TI  - Effects of Homelessness on Children.

PMID- 30275039
TI  - CME Quiz Correction.

PMID- 30275040
TI  - Visual Diagnosis: An Uncommon Presentation of a Common Rash.

PMID- 30275041
TI  - Reduced Activity of Geranylgeranyl Diphosphate Synthase Mutant Is Involved in
      Bisphosphonate-Induced Atypical Fractures.
AB  - Bisphosphonates are widely used for treating osteoporosis, a common disorder in
      which bone strength is reduced, increasing the risk for fractures. Rarely,
      bisphosphonates can paradoxically lead to atypical fractures occurring
      spontaneously or with trivial trauma. Recently, a novel missense mutation (D188Y)
      in the GGPS1 gene, encoding for geranylgeranyl diphosphate synthase (GGPPS), was
      associated with bisphosphonate-induced atypical fractures. However, the molecular
      basis for GGPPS involvement in this devastating condition remains elusive. Here,
      we show that while maintaining an overall unperturbed global enzyme structure,
      the D188Y mutation leads to ~4-fold catalytic activity decrease. Furthermore,
      GGPPS-D188Y is unable to support cross-species complementation, highlighting the
      functional significance of the reduced catalytic activity observed in vitro. We
      next determined the crystal structure of apo-GGPPS-D188Y, revealing that while
      Y188 does not alter the protein fold, its bulky side chain sterically interferes
      with substrate binding. In agreement, we show that GGPPS-D188Y exhibits ~3-fold
      reduction in the binding affinity of zoledronate, a commonly used bisphosphonate.
      However, inhibition of the mutated enzyme by zoledronate, in pharmacologically
      relevant concentrations, is maintained. Finally, we determined the crystal
      structure of zoledronate-bound GGPPS-D188Y, revealing large ligand-induced
      binding pocket rearrangements, revising the previous model for GGPPS
      bisphosphonate interactions. In conclusion, we propose that among heterozygotes
      residual GGPPS activity is sufficient to support physiologic cellular function,
      concealing any pathologic phenotype. However, under bisphosphonate treatment,
      GGPPS activity is reduced below a crucial threshold for osteoclast function,
      leading to impaired bone remodeling and increased susceptibility to atypical
      fractures.

PMID- 30275042
TI  - International Union of Basic and Clinical Pharmacology. CVI: GABAA Receptor
      Subtype- and Function-selective Ligands: Key Issues in Translation to Humans.
AB  - GABAA receptors are the major inhibitory transmitter receptors in the brain. They
      are ligand-gated chloride channels and the site of action of benzodiazepines,
      barbiturates, neuroactive steroids, anesthetics, and convulsants. GABAA receptors
      are composed of five subunits that can belong to different subunit classes. The
      existence of 19 homologous subunits and their distinct regional, cellular, and
      subcellular distribution gives rise to a large number of GABAA receptor subtypes
      with distinct pharmacology, which modulate different functions of the brain. A
      variety of compounds have been identified that were claimed to modulate
      selectively individual GABAA receptor subtypes. However, many of these compounds
      have only incompletely been investigated or, in addition to a preferential
      modulation of a receptor subtype, also modulate other subtypes at similar
      concentrations. Although their differential efficacy at distinct receptor
      subtypes reduced side effects in behavioral experiments in rodents, the exact
      receptor subtypes mediating their behavioral effects cannot be unequivocally
      delineated. In addition, the discrepant in vivo effects of some of these
      compounds in rodents and man raised doubts on the applicability of the concept of
      receptor subtype selectivity as a guide for the development of clinically useful
      drugs. Here, we provide an up-to-date review on the currently available GABAA
      receptor subtype-selective ligands. We present data on their actual activity at
      GABAA receptor subtypes, discuss the translational aspect of subtype-selective
      drugs, and make proposals for the future development of ligands with better
      anxioselectivity in humans. Finally, we discuss possible ways to strengthen the
      conclusions of behavioral studies with the currently available drugs.

PMID- 30275045
TI  - Corrigendum: p53 is essential for DNA methylation homeostasis in naive embryonic
      stem cells, and its loss promotes clonal heterogeneity.

PMID- 30275046
TI  - Cutting Edge: Local Proliferation of Uterine Tissue-Resident NK Cells during
      Decidualization in Mice.
AB  - NK cells accumulate in adult murine and human uteri during decidualization
      induced physiologically, pathologically, or experimentally. Adoptive transfer
      studies indicate that uterine NK (uNK) cells arise from circulating progenitors.
      However, virgin uteri contain few circulating NK1.1+CD49a- conventional NK cells,
      whereas NK1.1+CD49a+ tissue-resident NK (trNK) cells are abundant. In this study,
      we employed a novel, immune-competent NK cell-specific reporter mouse to track
      accumulation of uNK cells during unmanipulated pregnancies. We identified
      conventional NK and trNK cells accumulating in both decidua basalis and
      myometrium. Only trNK cells showed evidence of proliferation. In parabiosis
      studies using experimentally induced deciduomata, the accumulated uNK cells were
      proliferating trNK cells; migrating NK cells made no contribution. Together,
      these data suggest proliferating trNK cells are the source of uNK cells during
      endometrial decidualization.

PMID- 30275044
TI  - Pathways to balance mitochondrial translation and protein import.
AB  - Mitochondria contain their own genome that encodes for a small number of
      proteins, while the vast majority of mitochondrial proteins is produced on
      cytosolic ribosomes. The formation of respiratory chain complexes depends on the
      coordinated biogenesis of mitochondrially encoded and nuclear-encoded subunits.
      In this review, we describe pathways that adjust mitochondrial protein synthesis
      and import of nuclear-encoded subunits to the assembly of respiratory chain
      complexes. Furthermore, we outline how defects in protein import into
      mitochondria affect nuclear gene expression to maintain protein homeostasis under
      physiological and stress conditions.

PMID- 30275047
TI  - Lysyl-Transfer RNA Synthetase Induces the Maturation of Dendritic Cells through
      MAPK and NF-kappaB Pathways, Strongly Contributing to Enhanced Th1 Cell
      Responses.
AB  - In addition to essential roles in protein synthesis, lysyl-tRNA synthetase (KRS)
      is secreted to trigger a proinflammatory function that induces macrophage
      activation and TNF-alpha secretion. KRS has been associated with autoimmune
      diseases such as polymyositis and dermatomyositis. In this study, we investigated
      the immunomodulatory effects of KRS on bone marrow-derived dendritic cells (DCs)
      of C57BL/6 mice and subsequent polarization of Th cells and analyzed the
      underlying mechanisms. KRS-treated DCs increased the expression of cell surface
      molecules and proinflammatory cytokines associated with DC maturation and
      activation. Especially, KRS treatment significantly increased production of IL
      12, a Th1-polarizing cytokine, in DCs. KRS triggered the nuclear translocation of
      the NF-kappaB p65 subunit along with the degradation of IkappaB proteins and the
      phosphorylation of MAPKs in DCs. Additionally, JNK, p38, and ERK inhibitors
      markedly recovered the degradation of IkappaB proteins, suggesting the
      involvement of MAPKs as the upstream regulators of NF-kappaB in the KRS-induced
      DC maturation and activation. Importantly, KRS-treated DCs strongly increased the
      differentiation of Th1 cells when cocultured with CD4+ T cells. The addition of
      anti-IL-12-neutralizing Ab abolished the secretion of IFN-gamma in the coculture,
      indicating that KRS induces Th1 cell response via DC-derived IL-12. Moreover, KRS
      enhanced the OVA-specific Th1 cell polarization in vivo following the adoptive
      transfer of OVA-pulsed DCs. Taken together, these results indicated that KRS
      effectively induced the maturation and activation of DCs through MAPKs/NF-kappaB
      signaling pathways and favored DC-mediated Th1 cell response.

PMID- 30275048
TI  - EF Hand Domain Family Member D2 Is Required for T Cell Cytotoxicity.
AB  - Programmed cell death 1 (PD-1) is a major coinhibitory receptor and a member of
      the immunological synapse (IS). To uncover proteins that regulate PD-1
      recruitment to the IS, we searched for cytoskeleton-related proteins that also
      interact with PD-1 using affinity purification mass spectrometry. Among these
      proteins, EF hand domain family member D2 (EFHD2), a calcium binding adaptor
      protein, was functionally and mechanistically analyzed for its contribution to PD
      1 signaling. EFHD2 was required for PD-1 to inhibit cytokine secretion,
      proliferation, and adhesion of human T cells. Interestingly, EFHD2 was also
      required for human T cell-mediated cytotoxicity and for mounting an antitumor
      immune response in a syngeneic murine tumor model. Mechanistically, EFHD2
      contributed to IS stability, lytic vesicles trafficking, and granzyme B
      secretion. Altogether, EFHD2 is an important regulator of T cell cytotoxicity and
      further studies should evaluate its role in T cell-mediated inflammation.

PMID- 30275051
TI  - Sexual Inequality in the Cancer Cell.
AB  - Investigating sex differences in cancer will improve therapy for both sexes and
      discover sex-specific protective mechanisms. Two recent analyses by Lopes-Ramos
      and colleagues and Li and colleagues point to specific gene regulatory networks
      and genomic alterations associated with sex differences in tumor incidence and
      progression. Integrating this information with emerging concepts about sex biases
      in the genome may help focus attention on factors that shift the odds for tumor
      growth. Cancer Res; 78(19); 5504-5. (c)2018 AACR See related articles by Li et
      al., p. 5527, and Lopes-Ramos et al., p. 5538.

PMID- 30275043
TI  - Roles of the immune system in cancer: from tumor initiation to metastatic
      progression.
AB  - The presence of inflammatory immune cells in human tumors raises a fundamental
      question in oncology: How do cancer cells avoid the destruction by immune attack?
      In principle, tumor development can be controlled by cytotoxic innate and
      adaptive immune cells; however, as the tumor develops from neoplastic tissue to
      clinically detectable tumors, cancer cells evolve different mechanisms that mimic
      peripheral immune tolerance in order to avoid tumoricidal attack. Here, we
      provide an update of recent accomplishments, unifying concepts, and future
      challenges to study tumor-associated immune cells, with an emphasis on metastatic
      carcinomas.

PMID- 30275052
TI  - Sex Differences in Cancer Driver Genes and Biomarkers.
AB  - Cancer differs significantly between men and women; even after adjusting for
      known epidemiologic risk factors, the sexes differ in incidence, outcome, and
      response to therapy. These differences occur in many but not all tumor types, and
      their origins remain largely unknown. Here, we compare somatic mutation profiles
      between tumors arising in men and in women. We discovered large differences in
      mutation density and sex biases in the frequency of mutation of specific genes;
      these differences may be associated with sex biases in DNA mismatch repair genes
      or microsatellite instability. Sex-biased genes include well-known drivers of
      cancer such as beta-catenin and BAP1 Sex influenced biomarkers of patient
      outcome, where different genes were associated with tumor aggression in each sex.
      These data call for increased study and consideration of the molecular role of
      sex in cancer etiology, progression, treatment, and personalized
      therapy.Significance: This study provides a comprehensive catalog of sex
      differences in somatic alterations, including in cancer driver genes, which
      influence prognostic biomarkers that predict patient outcome after definitive
      local therapy. Cancer Res; 78(19); 5527-37. (c)2018 AACR.

PMID- 30275049
TI  - Proinflammatory Effects of Respiratory Syncytial Virus-Induced Epithelial HMGB1
      on Human Innate Immune Cell Activation.
AB  - High mobility group box 1 (HMGB1) is a multifunctional nuclear protein that
      translocates to the cytoplasm and is subsequently released to the extracellular
      space during infection and injury. Once released, it acts as a damage-associated
      molecular pattern and regulates immune and inflammatory responses. Respiratory
      syncytial virus (RSV) is a major cause of acute lower respiratory tract
      infections in infants and elderly, for which no effective treatment or vaccine is
      currently available. This study investigated the effects of HMGB1 on cytokine
      secretion, as well as the involvement of NF-kappaB and TLR4 pathways in RSV
      induced HMGB1 release in human airway epithelial cells (AECs) and its
      proinflammatory effects on several human primary immune cells. Purified HMGB1 was
      incubated with AECs (A549 and small alveolar epithelial cells) and various immune
      cells and measured the release of proinflammatory mediators and the activation of
      NF-kappaB and P38 MAPK. HMGB1 treatment significantly increased the
      phosphorylation of NF-kappaB and P38 MAPK but did not induce the release of
      cytokines/chemokines from AECs. However, addition of HMGB1 to immune cells did
      significantly induce the release of cytokines/chemokines and activated the NF
      kappaB and P38 MAPK pathways. We found that activation of NF-kappaB accounted for
      RSV-induced HMGB1 secretion in AECs in a TLR4-dependent manner. These results
      indicated that HMGB1 secreted from AECs can facilitate the secretion of
      proinflammatory mediators from immune cells in a paracrine mechanism, thus
      promoting the inflammatory response that contributes to RSV pathogenesis.
      Therefore, blocking the proinflammatory function of HMGB1 may be an effective
      approach for developing novel therapeutics.

PMID- 30275054
TI  - Correction: Targeting Vascular Endothelial-Cadherin in Tumor-Associated Blood
      Vessels Promotes T-cell-Mediated Immunotherapy.

PMID- 30275055
TI  - Retraction: Dicer Elicits Paclitaxel Chemosensitization and Suppresses Cancer
      Stemness in Breast Cancer by Repressing AXL.

PMID- 30275056
TI  - Micro imaging displays the sucrose landscape within and along its allocation
      pathways.
AB  - Sucrose is the major transport sugar in plants, and plays a primary role as an
      energy source and signal in adaptive and stress responses. An ability to quantify
      sucrose over time and space would serve to progress our understanding of these
      important processes. Current technologies used for sucrose mapping are unable to
      quantitatively visualize its distribution within tissues. Here, we present an
      infrared-based, microspectroscopic method that allows for the quantitative
      visualization of sucrose at a microscopic level of resolution (~12 um). This
      method can successfully model the sugar concentration in individual vascular
      bundles and within a complex organ such as the stem, leaf, or seed. The
      sensitivity of the assay ranges from 20 to 1000 mM. We applied this method to the
      cereal crop barley (Hordeum vulgare) and the model plant Arabidopsis thaliana to
      highlight the potential of the procedure for resolving the spatial distribution
      of metabolites. We also discuss the relevance of the method for studies on carbon
      allocation and storage in the context of crop improvement.

PMID- 30275053
TI  - Gene Regulatory Network Analysis Identifies Sex-Linked Differences in Colon
      Cancer Drug Metabolism.
AB  - Understanding sex differences in colon cancer is essential to advance disease
      prevention, diagnosis, and treatment. Males have a higher risk of developing
      colon cancer and a lower survival rate than women. However, the molecular
      features that drive these sex differences are poorly understood. In this study,
      we use both transcript-based and gene regulatory network methods to analyze RNA
      seq data from The Cancer Genome Atlas for 445 patients with colon cancer. We
      compared gene expression between tumors in men and women and observed significant
      sex differences in sex chromosome genes only. We then inferred patient-specific
      gene regulatory networks and found significant regulatory differences between
      males and females, with drug and xenobiotics metabolism via cytochrome P450
      pathways more strongly targeted in females. This finding was validated in a
      dataset of 1,193 patients from five independent studies. While targeting, the
      drug metabolism pathway did not change overall survival for males treated with
      adjuvant chemotherapy, females with greater targeting showed an increase in 10
      year overall survival probability, 89% [95% confidence interval (CI), 78-100]
      survival compared with 61% (95% CI, 45-82) for women with lower targeting,
      respectively (P = 0.034). Our network analysis uncovers patterns of
      transcriptional regulation that differentiate male and female colon cancer and
      identifies differences in regulatory processes involving the drug metabolism
      pathway associated with survival in women who receive adjuvant chemotherapy. This
      approach can be used to investigate the molecular features that drive sex
      differences in other cancers and complex diseases.Significance: A network-based
      approach reveals that sex-specific patterns of gene targeting by transcriptional
      regulators are associated with survival outcome in colon cancer. This approach
      can be used to understand how sex influences progression and response to
      therapies in other cancers. Cancer Res; 78(19); 5538-47. (c)2018 AACR.

PMID- 30275059
TI  - Have You Found Your Voice?

PMID- 30275060
TI  - In-Hospital Initiation of Guideline-Directed Heart Failure Pharmacotherapy to
      Improve Long-Term Patient Adherence and Outcomes.
AB  - Heart failure is a burdensome cardiovascular condition associated with high rates
      of morbidity and mortality. The 3-month period after hospitalization is a
      vulnerable phase in which patients are at high risk for mortality and
      rehospitalization. To reduce risk during this period, patients with heart failure
      and reduced ejection fraction should receive guideline-directed pharmacological
      therapies-the right drugs at the right doses-before hospital discharge. Optimal
      pharmacotherapies for these patients include agents that suppress the renin
      angiotensin-aldosterone system, suppress the sympathetic nervous system, enhance
      vasodilation, slow heart rate when needed, and reduce excess volume. Because
      optimal prescription and adherence are both necessary to ensure the best clinical
      outcomes, nurses need to participate in interventions that optimize prescription
      and drug use over time. Collaboration with pharmacists and advanced practice
      acute care nurses may help ensure that medication selection and dosing are
      consistent with national guidelines. Use of a predischarge order set and
      electronic medical records checklist can enhance collaborative care.

PMID- 30275057
TI  - Time-Course Transcriptome Analysis of Arabidopsis Siliques Discloses Genes
      Essential for Fruit Development and Maturation.
AB  - Fruits protect the developing seeds of angiosperms and actively contribute to
      seed dispersion. Furthermore, fruit and seed development are highly synchronized
      and require exchange of information between the mother plant and the developing
      generations. To explore the mechanisms controlling fruit formation and
      maturation, we performed a transcriptomic analysis on the valve tissue of the
      Arabidopsis (Arabidopsis thaliana) silique using RNA sequencing. In doing so, we
      have generated a data set of differentially regulated genes that will help to
      elucidate the molecular mechanisms that underpin the initial phase of fruit
      growth and, subsequently, trigger fruit maturation. The robustness of our data
      set has been tested by functional genomic studies. Using a reverse genetics
      approach, we selected 10 differentially expressed genes and explored the
      consequences of their disruption for both silique growth and senescence. We found
      that genes contained in our data set play essential roles in different stages of
      silique development and maturation, indicating that our transcriptome-based gene
      list is a powerful tool for the elucidation of the molecular mechanisms
      controlling fruit formation in Arabidopsis.

PMID- 30275061
TI  - The Intranasal Route as an Alternative Method of Medication Administration.
AB  - Intranasal drug administration is a less invasive method of drug delivery that is
      easily accessible for adult and pediatric patients. Medications administered by
      the intranasal route have efficacy comparable to intravenous administration and
      typically have superior efficacy to subcutaneous or intramuscular routes. The
      intranasal route is beneficial in emergent situations when the intravenous route
      is not available. The intranasal route is safe and effective in various
      indications, and therapeutic systemic concentrations of medication can be
      attained via this route. As the evidence for and comfort with intranasal
      administration continue to grow, guidance on correct technique, medications, and
      dosing is vital for appropriate use. This article reviews the process and
      practices of appropriate intranasal medication administration.

PMID- 30275058
TI  - Root Gravitropism Is Regulated by a Crosstalk between para-Aminobenzoic Acid,
      Ethylene, and Auxin.
AB  - Plants respond to gravitational force through directional growth along the
      gravity vector. Although auxin is the central component of the root
      graviresponse, it works in concert with other plant hormones. Here, we show that
      the folate precursor para-aminobenzoic acid (PABA) is a key modulator of the
      auxin-ethylene interplay during root gravitropism in Arabidopsis (Arabidopsis
      thaliana). In gravistimulated roots, PABA promotes an asymmetric auxin response,
      which causes the asymmetric growth responsible for root curvature. This activity
      requires the auxin response transcription factors AUXIN RESPONSE FACTOR7 (ARF7)
      and ARF19 as well as ethylene biosynthesis and signaling, indicating that PABA
      activity requires both auxin and ethylene pathways. Similar to ethylene,
      exogenous PABA reverses the agravitropic root growth of the auxin transport
      mutant pin-formed2 (pin2) and the auxin biosynthetic double mutant with loss of
      function of weak ethylene insensitive (wei) genes, wei8wei2, but not the
      pin2wei8wei2 triple mutant. This finding suggests that PABA regulates the
      ethylene-dependent reciprocal compensation between auxin transport and
      biosynthesis. Furthermore, manipulation of endogenous free PABA levels by
      modulating the expression of the gene encoding its glucosylation enzyme, UDP
      GLYCOSYL TRANSFERASE75B1, impacts the root graviresponse, suggesting that
      endogenous free PABA levels may play a crucial role in modulating the auxin
      ethylene cross talk necessary for root gravitropism.

PMID- 30275062
TI  - Implementation of a Clinical Pathway to Reduce Rates of Postextubation Stridor.
AB  - BACKGROUND: Unsuccessful extubation is associated with increased intensive care
      unit and hospital length of stays, hospital costs, morbidity, and mortality. The
      most common cause of reintubation is laryngeal edema, often evidenced by
      postextubation stridor. OBJECTIVE: To reduce the rates of postextubation stridor
      and reintubation in the neurocritical care unit at a large urban academic medical
      center. METHODS: A clinical pathway was created to aid in detecting patients
      expected to experience postextubation stridor and to guide prophylactic
      treatment. During the 12-week implementation phase, the pathway was completed on
      all intubated patients daily. RESULTS: The 12-week trial included a total of 606
      days of mechanical ventilation. Checklists were completed for 531 days, a
      compliance rate of 88% for use of the clinical pathway. Of the 56 patients who
      were extubated during the trial, 54 had a checklist completed, for 96% compliance
      on the day of extubation. Outcomes after all nonpalliative extubations (n = 43)
      during the 12 weeks before and after implementation of the pathway (n = 56
      periods) were evaluated by using chi 2 tests. Implementation of the pathway was
      associated with a significant reduction in rates of postextubation stridor (chi 2
      = 6.2; P = .01), reintubation (chi 2 = 5.5; P = .02), and reintubation due to
      postextubation stridor (chi 2 = 8.3; P = .004). CONCLUSION: The clinical pathway
      implemented in the neurocritical care unit was safe and effective in reducing
      rates of reintubation and reintubation due to postextubation stridor.

PMID- 30275063
TI  - Caring for Pediatric Heart Failure Patients With Long-Term Mechanical Circulatory
      Support.
AB  - Pediatric cardiac failure is a significant problem that may be caused by
      cardiomyopathy, myocarditis, or congenital defects that cannot be surgically
      repaired. Long-term mechanical circulatory support (LTMCS) devices provide
      hemodynamic support for patients in heart failure as a bridge to heart transplant
      and, sometimes, cardiac recovery or destination therapy. Critical care nurses
      must have a comprehensive understanding of LTMCS device function and keen
      assessment skills to detect signs of impaired perfusion and device failure.
      Nurses should anticipate postoperative interventions, prevent adverse events, and
      be prepared to respond during emergencies. Patient care should be family centered
      and nurses must strive to maximize patients' quality of life throughout device
      implantation. This article provides a basic guide to caring for pediatric
      patients receiving LTMCS, including specific information regarding 4 devices that
      are often used for pediatric heart failure: Berlin Heart EXCOR, SynCardia Total
      Artificial Heart, HeartWare HVAD, and HeartMate II.

PMID- 30275064
TI  - Automated Audiovisual Feedback in Cardiopulmonary Resuscitation Training:
      Improving Skills in Pediatric Intensive Care Nurses.
AB  - BACKGROUND: High-quality cardiopulmonary resuscitation is associated with
      improved survival and neurological outcomes after cardiac arrest. Unfortunately,
      health care professionals frequently do not perform resuscitation within
      guidelines after life-support training. OBJECTIVES: To determine if brief
      intermittent training in cardiopulmonary resuscitation could improve nurses'
      skills to perform high-quality resuscitation 70% or more of the time during 2
      minutes of cardiopulmonary resuscitation after 3 training sessions. METHODS: In a
      prospective single-center quality improvement program, pediatric critical care
      nurses had monthly training in cardiopulmonary resuscitation. A portable
      manikin/defibrillator with a chest compression sensor was used to provide
      corrective audiovisual feedback to optimize resuscitation skills. Resuscitation
      was practiced on an adult manikin. Target goals were compression depth 2 in or
      greater at a compression rate of 100/min to 120/minute. Percentage of time in the
      target range and mean compression depth and rate were recorded. Data were
      collected every other month. The percentage of time both compression rate and
      depth were in the target range was compared among nurses with different total
      numbers of training sessions. RESULTS: Of the 62 nurses who participated in the
      training, 48 had data collected. The median percentage of time in the target
      range improved from 29% with no training to 46% after 1 session, 54% after 2
      sessions, 68% after 3 sessions, and 74% after 4 sessions (P = .001). Compression
      depth increased with the number of training sessions (P = .002). CONCLUSIONS:
      This training program in cardiopulmonary resuscitation yielded significant skill
      improvement and retention.

PMID- 30275065
TI  - Value the Journey.

PMID- 30275066
TI  - Mechanical Ventilator Modes.

PMID- 30275068
TI  - Accurate Dysrhythmia Monitoring in Adults.

PMID- 30275067
TI  - Transitions in Care From Acute Care Telemetry Unit to Home: An Evidence-Based
      Quality Improvement Project.

PMID- 30275069
TI  - Hyperlactatemia and Patient Outcomes After Pediatric Cardiac Surgery.
AB  - Elevated serum lactate level, or hyperlactatemia, is often associated with
      alterations in tissue perfusion, increased risk for complications in the
      postoperative period, and patient mortality. Measuring lactate levels is a
      relatively simple and noninvasive method of obtaining useful data about an
      impending clinical deterioration in a seemingly hemodynamically stable patient.
      This article evaluates the current practice of measuring lactate levels in
      pediatric patients after cardiac surgery and the association between these levels
      and patient outcomes. The article addresses periods of increased risk for
      decreased perfusion, the critical postoperative period, use of lactate
      measurements in conjunction with a risk scoring system for pre-and postoperative
      congenital heart disease patients, and the implications of elevated lactate
      levels in nursing practice.

PMID- 30275070
TI  - Congenital Cardiac Defects That Are Borderline Candidates for Biventricular
      Repair.
AB  - This article discusses congenital heart defects that are marginal candidates for
      biventricular repair and highlights the anatomic considerations upon which the
      surgical decision is based. Specifically, the article reviews the importance of
      capacitance and compliance of the ventricles and their associated
      atrioventricular valves. For each of the defects discussed, the imaging
      modalities used to diagnose a marginal ventricle are reviewed and the surgical
      decision-making process is outlined. The article also reviews immediate
      postoperative treatment of these patients and when to consider biventricular
      repair of a marginal lesion to be a failure.

PMID- 30275071
TI  - Erratum: Electrophoretic Mobility Shift Assays for RNA-Protein Complexes.

PMID- 30275072
TI  - DAPI Staining of Whole-Mount Mouse Embryos or Fetal Organs.
AB  - Mouse embryos and fetal organs have no pigmentation except for the retinal
      pigmented epithelium of the eye at subsequent stages of development. This makes
      it difficult to visualize and photodocument embryonic structures using
      conventional light microscopy. A simple method is provided here that uses
      fluorescent nuclear stains. At the relatively low magnifications of dissecting
      microscopes, the nuclei of embryonic tissues essentially become "pixels" of
      fluorescence that "paint" the embryo, providing images similar to those obtained
      by low-magnification scanning electron microcopy (SEM). This method can be
      applied to standardly fixed whole embryos at least up to embryonic Day 14.5
      (E14.5), and to embryos that have been processed for whole-embryo in situ
      hybridization and immunostaining. Dissected tissues and organs (e.g., palate,
      heart, lungs, gastrointestinal tract) may also be stained and visualized with
      this technique.

PMID- 30275073
TI  - Immunofluorescent Staining of Whole-Mount Mouse Embryos.
AB  - Mouse embryos and fetal organs have no pigmentation except for the retinal
      pigmented epithelium of the eye at subsequent stages of development. This makes
      it difficult to visualize and photodocument embryonic structures using
      conventional light microscopy. This protocol is used to localize specific
      proteins in whole embryos or fetal organs using immunofluorescence. Various
      imaging modalities can then be used to visualize these expression patterns, for
      example, confocal microscopy or optical projection tomography.

PMID- 30275074
TI  - Optimizing Primer and Probe Concentrations for Use in Real-Time Polymerase Chain
      Reaction (PCR) Assays.
AB  - Once primers and probes have been designed and obtained, it is necessary to
      optimize their concentration for each real-time polymerase chain reaction (PCR)
      assay. A set of PCRs is assembled in which the concentrations of forward and
      reverse primers are varied independently. Following amplification of the template
      DNA, amplification plots are compared. A standard curve is generated to determine
      the efficiency, sensitivity, and reproducibility of the assay. If SYBR Green I is
      used as the probe, then the melting curves are also analyzed.

PMID- 30275075
TI  - Constructing a Standard Curve for Real-Time Polymerase Chain Reaction (PCR)
      Experiments.
AB  - It is essential to prepare a standard curve for every real-time polymerase chain
      reaction (PCR) experiment. This protocol is used to construct a standard curve in
      which the template concentration is unknown. Such a standard curve is suitable
      for optimization experiments and for performing relative quantification by the
      standard curve method. To construct a standard curve for absolute quantification,
      the same principles apply as those presented here, but the concentration of the
      standards must be determined by an independent method.

PMID- 30275076
TI  - Quantification of DNA by Real-Time Polymerase Chain Reaction (PCR).
AB  - There are few differences between the experimental steps necessary for amplifying
      template DNA in a real-time thermocycler and a standard polymerase chain reaction
      (PCR). In real-time PCR, it is necessary, however, to optimize the concentration
      of primers and probe and to perform a standard curve. It is also important to
      consider the data analysis method that will be used.

PMID- 30275077
TI  - Quantification of RNA by Real-Time Reverse Transcription-Polymerase Chain
      Reaction (RT-PCR).
AB  - This protocol describes a real-time reverse transcription-polymerase chain
      reaction (RT-PCR) assay using a two-enzyme, two-tube approach, carried out using
      either SYBR Green I or TaqMan chemistries. The protocol uses a PCR volume of 20
      uL (although most manufacturers recommend 50-uL reactions). However, if the PCR
      target is not very abundant (i.e., present at one to 10 copies per sample), a
      larger volume may yield better reproducibility between samples. Discussion on
      preparing high-quality RNA, choosing a priming method, selecting an enzyme, and
      selecting an endogenous reference gene is also included.

PMID- 30275078
TI  - Resolving Proteins for Immunoblotting by Gel Electrophoresis.
AB  - This protocol describes Tris/glycine SDS-polyacrylamide gel electrophoresis, also
      known as SDS discontinuous gel electrophoresis or the Laemmli electrophoresis
      system. The gel-casting unit is assembled and tested to make sure that there are
      no leaks. Ammonium persulfate and tetramethylethylenediamine are added to the
      separating monomer solution, and the bottom (separating) gel is poured and
      allowed to polymerize. The top (stacking) gel is poured, and the comb is inserted
      to make the wells. The stacking gel is allowed to polymerize and the comb is then
      removed. The gel cassette is connected to the buffer chambers and the samples are
      loaded into the wells. When the electric current is applied, the proteins migrate
      through the gel with a rate that is roughly proportional to the length of their
      polypeptide chains. The electrophoresis is stopped when the loading dye reaches
      the bottom of the separating gel. The gel cassette is disassembled, and the
      proteins are ready for transfer from the gel onto the membrane.

PMID- 30275079
TI  - Immunoblotting: Transfer of Proteins from Gels to Membranes.
AB  - Electrophoretic transfer of proteins from gels to membranes can be achieved
      either by complete immersion of a gel-membrane sandwich in a buffer (wet
      transfer) or by placing the gel-membrane sandwich between absorbent paper soaked
      in transfer buffer (semidry transfer). For the wet transfer, the sandwich is
      placed in a buffer tank with platinum wire electrodes. For the semidry transfer,
      the gel-membrane sandwich is placed between carbon plate or stainless steel
      electrodes. Both methods are described here and generally work well, although
      semidry transfer is quicker and often more complete.

PMID- 30275080
TI  - Making Weak Antigens Strong: Cross-Linking Peptides to KLH with Maleimide.
AB  - Haptens, which are small antigens such as peptides and drug compounds, are very
      weakly or nonimmunogenic by themselves and require the assistance of carrier
      proteins: complex molecules capable of eliciting a strong immune response in the
      host on injection. The haptens serve as epitopes for binding to the antibodies on
      the B-cell surface, and the carriers provide the MHC class II-T-cell receptor
      binding sites. Keyhole limpet hemocyanin (KLH) is one of the most widely used of
      such carrier proteins. KLH-hapten conjugates are commonly used in antibody
      generation in a variety of hosts such as mice, rats, and rabbits. Because KLH is
      harvested from mollusks, it is physiologically distant from mammalian species and
      less likely to produce antibodies that cross-react mammalian antigens. Maleimide
      activation of carrier proteins makes it possible to conjugate sulfhydryl
      containing haptens, and hence this chemistry is widely used for conjugating KLH
      with haptens.

PMID- 30275081
TI  - Analysis and Normalization of Real-Time Polymerase Chain Reaction (PCR)
      Experimental Data.
AB  - In real-time polymerase chain reaction (PCR), also called quantitative real-time
      PCR [or simply quantitative PCR (qPCR)] or kinetic PCR, the amplification of DNA
      is monitored by the detection and quantitation of a fluorescent reporter signal,
      which increases in direct proportion to the amount of PCR product in the
      reaction. The fluorescent reporter is excited by light from the real-time PCR
      machine, a fluorescence-detecting thermocycler. By recording the amount of
      fluorescence emission at each cycle, the PCR can be monitored during the
      exponential phase when the first significant increase in the amount of PCR
      product correlates with the initial amount of target template. The ability to
      quantify the amplified DNA during the exponential phase of the PCR, when none of
      the components of the reaction is limiting, has resulted in dramatically improved
      precision in the quantitation of target sequences. In addition, because of the
      high sensitivity of fluorometric detection, real-time PCR is capable of measuring
      the initial concentration of target DNA over a vast dynamic range (up to eight or
      nine orders of magnitude) and with a high degree of sensitivity (as little as one
      copy of template DNA). Although it is a powerful technique, researchers often
      face challenges in reliability and reproducibility because of the lack of assay
      standardization. Therefore, it is critical to optimize the reagents and reaction
      conditions, include proper internal and external controls, and perform rigorous
      data analysis in order to generate accurate and reproducible results in real-time
      PCR experiments.

PMID- 30275082
TI  - High Rate of Ceftobiprole Resistance among Clinical Methicillin-Resistant
      Staphylococcus aureus Isolates from a Hospital in Central Italy.
AB  - Ceftobiprole is a fifth-generation cephalosporin with activity against
      methicillin-resistant Staphylococcus aureus (MRSA). One-year surveillance at the
      Regional Hospital of Ancona (Italy) disclosed a 12% ceftobiprole resistance rate
      (12/102 isolates; MIC, >=4 mg/liter). Epidemiological characterization
      demonstrated that the resistant isolates all belonged to different clones.
      Penicillin-binding protein (PBP) analysis showed substitutions in all PBPs and a
      novel insertion in PBP2a. The mecB and mecC genes were not detected. Ceftobiprole
      susceptibility screening is essential to avoid therapeutic failure and the spread
      of ceftobiprole-resistant strains.

PMID- 30275083
TI  - Efficacious Analogs of the Lantibiotic Mutacin 1140 against a Systemic
      Methicillin-Resistant Staphylococcus aureus Infection.
AB  - Mutacin 1140, a member of the epidermin family of type AI lantibiotics, has a
      broad spectrum of activity against Gram-positive bacteria. It blocks cell wall
      synthesis by binding to lipid II. Although it has rapid bactericidal effects and
      potent activity against Gram-positive pathogens, its rapid clearance and short
      half-life in vivo limit its development in the clinic. In this study, we
      evaluated the effect of charged and dehydrated residues on the pharmacokinetics
      of mutacin 1140. The dehydrated residues were determined to contribute to the
      stability of mutacin 1140, while alanine substitutions for the lysine or arginine
      residues improved the pharmacological properties of the antibiotic. Analogs K2A
      and R13A had significantly lower clearances, leading to higher plasma
      concentrations over time. They also had improved bioactivities against several
      pathogenic bacteria. In a murine systemic methicillin-resistant Staphylococcus
      aureus (MRSA) infection model, a 10-mg/kg single intravenous bolus injection of
      the K2A and R13A analogs (1:1 ratio) protected 100% of the infected mice, while a
      2.5-mg/kg dose resulted in 50% survival. The 10-mg/kg treatment group had a
      significant reduction in bacteria load in the livers and kidneys compared to that
      in the vehicle control group. The study provides lead compounds for the future
      development of antibiotics used to treat systemic Gram-positive infections.

PMID- 30275084
TI  - Selective Inhibition of Neisseria gonorrhoeae by a Dithiazoline in Mixed
      Infections with Lactobacillus gasseri.
AB  - The Gram-negative human pathogen Neisseria gonorrhoeae has progressively
      developed resistance to antibiotic monotherapies, and recent failures of dual
      drug therapy have heightened concerns that strains resistant to all available
      antibiotics will begin circulating globally. Targeting bacterial cell wall
      assembly has historically been effective at treating infections with N.
      gonorrhoeae, but as the effectiveness of beta-lactams (including cephalosporins)
      is challenged by increasing resistance, research has expanded into compounds that
      target the numerous other enzymes with roles in peptidoglycan metabolism. One
      example is the dithiazoline compound JNJ-853346 (DTZ), which inhibits the
      activity of an Escherichia coli serine protease l,d-carboxypeptidase (LdcA).
      Recently, the characterization of an LdcA homolog in N. gonorrhoeae revealed
      localization and activity differences from the characterized E. coli LdcA,
      prompting us to explore the effectiveness of DTZ against N. gonorrhoeae We found
      that DTZ is effective at inhibiting N. gonorrhoeae in all growth phases, unlike
      the specific stationary-phase inhibition seen in E. coli Surprisingly, DTZ does
      not inhibit gonococcal LdcA enzyme activity, and DTZ sensitivity is not
      significantly decreased in ldcA mutants. While effective against numerous N.
      gonorrhoeae strains, including recent multidrug-resistant isolates, DTZ is much
      less effective at inhibiting growth of the commensal species Lactobacillus
      gasseri DTZ treatment during coinfections of epithelial cells resulted in
      significant lowering of gonococcal burden and interleukin-8 secretion without
      significantly impacting recovery of viable L. gasseri This selective toxicity
      presents a possible pathway for the use of DTZ as an effective antigonococcal
      agent at concentrations that do not impact vaginal commensals.

PMID- 30275085
TI  - Nitazoxanide Is a Therapeutic Option for Adenovirus-Related Enteritis in
      Immunocompromised Adults.

PMID- 30275086
TI  - Emergence of Klebsiella pneumoniae Harboring the aac(6')-Ian Amikacin Resistance
      Gene.

PMID- 30275087
TI  - Pentoxifylline Alone or in Combination with Gentamicin or Vancomycin Inhibits
      Live Microbe-Induced Proinflammatory Cytokine Production in Human Cord Blood and
      Cord Blood Monocytes In Vitro.
AB  - Neonatal sepsis and its accompanying inflammatory response contribute to
      substantial morbidity and mortality. Pentoxifylline (PTX), a phosphodiesterase
      inhibitor which suppresses transcription and production of proinflammatory
      cytokines, is a candidate adjunctive therapy for newborn sepsis. We hypothesized
      that PTX decreases live microbe-induced inflammatory cytokine production in
      newborn blood. Cord blood was stimulated with live microorganisms commonly
      encountered in newborn sepsis (Escherichia coli, Staphylococcus aureus,
      Staphylococcus epidermidis, or Candida albicans) and simultaneously treated with
      antimicrobial agents (gentamicin, vancomycin, or amphotericin B) and/or
      clinically relevant concentrations of PTX. Microbial colony counts were
      enumerated by plating, supernatant cytokines were measured by multiplex assay,
      intracellular cytokines and signaling molecules were measured by flow cytometry,
      and mRNA levels were measured by quantitative reverse transcription-PCR. PTX
      inhibited concentration-dependent E. coli-, S. aureus-, S. epidermidis-, and C.
      albicans-induced tumor necrosis factor (TNF) and E. coli-induced interleukin
      1beta (IL-1beta) production in whole blood, with greater suppression of
      proinflammatory cytokines in combination with antimicrobial agents. Likewise, PTX
      suppressed E. coli-induced monocytic TNF and IL-1beta, whereby combined PTX and
      gentamicin led to significantly greater reduction of TNF and IL-1beta. The anti
      inflammatory effect of PTX on microbe-induced proinflammatory cytokine production
      was accompanied by inhibition of TNF mRNA expression and was achieved without
      suppressing the production of the anti-inflammatory IL-10. Of note, microbial
      colony counts in newborn blood were not increased by PTX. Our findings
      demonstrated that PTX inhibited microbe-induced proinflammatory cytokine
      production, especially when combined with antimicrobial agents, without enhancing
      microbial proliferation in human cord blood in vitro, thus supporting its utility
      as candidate adjunctive agent for newborn sepsis.

PMID- 30275088
TI  - Trichlorination of a Teicoplanin-Type Glycopeptide Antibiotic by the Halogenase
      StaI Evades Resistance.
AB  - Glycopeptide antibiotics (GPAs) include clinically important drugs used for the
      treatment of infections caused by Gram-positive pathogens. These antibiotics are
      specialized metabolites produced by several genera of actinomycete bacteria.
      While many GPAs are highly chemically modified, A47934 is a relatively unadorned
      GPA lacking sugar or acyl modifications, common to other members of the class,
      but which is chlorinated at three distinct sites. The biosynthesis of A47934 is
      encoded by a 68-kb gene cluster in Streptomyces toyocaensis NRRL 15009. The
      cluster includes all necessary genes for the synthesis of A47934, including two
      predicted halogenase genes, staI and staK In this study, we report that only one
      of the halogenase genes, staI, is necessary and essential for A47934
      biosynthesis. Chlorination of the A47934 scaffold is important for antibiotic
      activity, as assessed by binding affinity for the target N-acyl-d-Ala-d-Ala.
      Surprisingly, chlorination is also vital to avoid activation of enterococcal and
      Streptomyces VanB-type GPA resistance through induction of resistance genes.
      Phenotypic assays showed stronger induction of GPA resistance by the
      dechlorinated compared to the chlorinated GPA. Correspondingly, the relative
      expression of the enterococcal vanA resistance gene was shown to be increased by
      the dechlorinated compared to the chlorinated compound. These results provide
      insight into the biosynthesis of GPAs and the biological function of GPA
      chlorination for this medically important class of antibiotic.

PMID- 30275089
TI  - Emergence and Within-Host Genetic Evolution of Methicillin-Resistant
      Staphylococcus aureus Resistant to Linezolid in a Cystic Fibrosis Patient.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) infection has increased in
      recent years among cystic fibrosis (CF) patients. Linezolid (LZD) is one of the
      antistaphylococcal antibiotics widely used in this context. Although LZD
      resistance is rare, it has been described as often associated with long-term
      treatments. Thirteen MRSA strains isolated over 5 years from one CF patient were
      studied for LZD resistance emergence and subjected to whole-genome sequencing
      (WGS). Resistance emerged after three 15-day LZD therapeutic regimens over 4
      months. It was associated with the mutation of G to T at position 2576 (G2576T)
      in all 5 rrl copies, along with a very high MIC (>256 mg/liter) and a strong
      increase in the generation time. Resistant strains isolated during the ensuing
      LZD therapeutic regimens and until 13 months after LZD stopped harbored only 3 or
      4 mutated rrl copies, associated with lower MICs (8 to 32 mg/liter) and low to
      moderate generation time increases. Despite these differences, whole-genome
      sequencing allowed us to determine that all isolates, including the susceptible
      one isolated before LZD treatment, belonged to the same lineage. In conclusion,
      LZD resistance can emerge rapidly in CF patients and persist without linezolid
      selective pressure in colonizing MRSA strains belonging to the same lineage.

PMID- 30275090
TI  - Correlation of In Vitro Susceptibility Based on MICs and Squalene Epoxidase
      Mutations with Clinical Response to Terbinafine in Patients with Tinea
      Corporis/Cruris.
AB  - Recalcitrant dermatophytoses are on the rise in India. High MICs of terbinafine
      (TRB) and squalene epoxidase (SQLE) gene mutations conferring resistance in
      Trichophyton spp. have been recently documented. However, studies correlating
      laboratory data with clinical response to TRB in tinea corporis/cruris are
      lacking. For this study, we investigated the clinicomycological profile of 85
      tinea corporis/cruris patients and performed antifungal susceptibility testing by
      CLSI microbroth dilution and SQLE mutation analysis of the isolates obtained and
      correlated these with the responses to TRB. Patients confirmed by potassium
      hydroxide (KOH) mounting of skin scrapings were started on TRB at 250 mg once a
      day (OD). If >50% clinical clearance was achieved by 3 weeks, the same dose was
      continued (group 1). If response was <50%, the dose was increased to 250 mg twice
      a day (BD) (group 2). If the response still remained below 50% after 3 weeks of
      BD, the patients were treated with itraconazole (ITR; group 3). Overall, skin
      scrapings from 64 (75.3%) patients yielded growth on culture. Strikingly, all
      isolates were confirmed to be Trichophyton interdigitale isolates by internal
      transcribed spacer (ITS) sequencing. Thirty-nine (61%) of the isolates had TRB
      MICs of >=1 ug/ml. Complete follow-up data were available for 30 culture-positive
      patients. A highly significant difference in modal MICs to TRB among the three
      treatment response groups was noted (P = 0.009). Interestingly, 8 of the 9
      patients in group 3 harbored isolates exhibiting elevated TRB MICs (8 to 32
      ug/ml) and SQLE mutations. The odds of achieving cure with TRB MIC < 1 ug/ml
      strains were 2.5 times the odds of achieving cure with the strain exhibiting MIC
      >=1 ug/ml.

PMID- 30275091
TI  - Pharmacokinetics of Intravenous Isavuconazole in Solid-Organ Transplant
      Recipients.
AB  - Isavuconazole may be useful in treating and preventing fungal infections in solid
      organ transplant (SOT) recipients due to its safety profile and activity against
      Aspergillus and some Mucorales Isavuconazole has favorable pharmacokinetics based
      on clinical trials in various patient populations, but data are limited in SOT
      recipients. We evaluated the steady-state pharmacokinetics of isavuconazole in 26
      SOT recipients receiving the drug intravenously for prophylaxis. There was
      moderate interpatient variability in isavuconazole pharmacokinetic parameters
      (coefficients of variation of 51% for the area under the plasma concentration
      versus-time curve [AUC] and 59% for the trough plasma concentration [C trough]).
      AUC and steady-state C trough were significantly lower in women, patients with a
      body mass index of >=18.5 kg/m2, and those receiving hemodialysis. Trough plasma
      concentrations were highly correlated with AUCs (R 2 = 0.94) and can serve as a
      suitable measure of isavuconazole exposure in patients. In conclusion, moderate
      interpatient variability in isavuconazole exposure, the identification of factors
      associated with lower exposure, the recognition that C trough is a surrogate
      marker for AUC, and the availability of a simple analytical method suggest that
      therapeutic drug monitoring (TDM) may be useful for guiding treatment in at least
      some SOT recipients. Future studies are needed to correlate isavuconazole
      exposure with patients' clinical outcomes and to determine the clinical role of
      TDM.

PMID- 30275092
TI  - A Phase 1 Study To Assess the Pharmacokinetics of Intravenous Plazomicin in Adult
      Subjects with Varying Degrees of Renal Function.
AB  - Plazomicin is an FDA-approved aminoglycoside for the treatment of complicated
      urinary tract infections. In this open-label study, 24 adults with normal renal
      function or mild, moderate, or severe renal impairment (n = 6 per group) received
      a single 7.5-mg/kg of body weight dose of plazomicin as a 30-min intravenous
      infusion. Total clearance declined with renal impairment, resulting in 1.98-fold
      and 4.42-fold higher plazomicin exposures, as measured by the area under the
      concentration-time curve from 0 h to infinity, in subjects with moderate and
      severe impairment, respectively, than in subjects with normal renal function.
      (This study has been registered at ClinicalTrials.gov under identifier
      NCT01462136.).

PMID- 30275093
TI  - Antimicrobial Susceptibility of 260 Clostridium botulinum Type A, B, Ba, and Bf
      Strains and a Neurotoxigenic Clostridium baratii Type F Strain Isolated from
      California Infant Botulism Patients.
AB  - Infant botulism is an infectious intestinal toxemia that results from
      colonization of the infant large bowel by Clostridium botulinum (or rarely, by
      neurotoxigenic Clostridium baratii or Clostridium butyricum), with subsequent
      intraintestinal production and absorption of botulinum neurotoxin that then
      produces flaccid paralysis. The disease is often initially misdiagnosed as
      suspected sepsis or meningitis, diagnoses that require prompt empirical
      antimicrobial therapy. Antibiotics may also be needed to treat infectious
      complications of infant botulism, such as pneumonia or urinary tract infection.
      Clinical evidence suggests (see case report below) that broad-spectrum
      antibiotics that are eliminated by biliary excretion may cause progression of the
      patient's paralysis by lysing C. botulinum vegetative cells in the large bowel
      lumen, thereby increasing the amount of botulinum neurotoxin available for
      absorption. The purpose of this antimicrobial susceptibility study was to
      identify an antimicrobial agent with little or no activity against C. botulinum
      that could be used to treat infant botulism patients initially diagnosed with
      suspected sepsis or meningitis, or who acquired secondary infections, without
      lysing C. botulinum Testing of 12 antimicrobial agents indicated that almost all
      California infant botulism patient isolates are susceptible to most clinically
      utilized antibiotics and are also susceptible to newer antibiotics not previously
      tested against large numbers of C. botulinum patient isolates. No antibiotic with
      little or no activity against C. botulinum was identified. These findings
      reinforce the importance of promptly treating infant botulism patients with human
      botulism immune globulin (BIG-IV [BabyBIG]).

PMID- 30275094
TI  - Tenofovir Exposure during Pregnancy and Postpartum in Women Receiving Tenofovir
      Disoproxil Fumarate for the Prevention of Mother-to-Child Transmission of
      Hepatitis B Virus.
AB  - We assessed tenofovir exposure during pregnancy and postpartum in hepatitis B
      virus (HBV)-infected HIV-uninfected women receiving tenofovir disoproxil fumarate
      (TDF) to prevent mother-to-child transmission of HBV. Data from 154 women who
      received TDF within a randomized controlled trial were included. Individual
      plasma tenofovir exposures (area under the concentration-time curve from 0 to 24
      h [AUC0-24]) were estimated using a population pharmacokinetic approach. The
      estimated geometric mean tenofovir AUC0-24 was 20% (95% confidence interval [95%
      CI], 19 to 21%) lower during pregnancy than during postpartum; this modest
      reduction in the absence of HBV transmission suggests that no dose adjustment is
      needed.

PMID- 30275096
TI  - Barriers to the release of human tissue for clinical trials research in the UK: a
      national survey of cellular pathology laboratories on behalf of the National
      Cancer Research Institute's Cellular Molecular Pathology (CM-Path) initiative.
AB  - AIM: To survey UK cellular pathology departments regarding their attitudes and
      practices relating to release of human tissue from their diagnostic archives for
      use in clinical trial research. METHODS: A 30-item questionnaire was circulated
      to the National Cancer Research Institute's Cellular Molecular Pathology
      initiative and Confederation of Cancer Biobanks mailing lists. Responses were
      collected over a 10-month period from November 2016 to August 2017. RESULTS: 38
      departments responded to the survey, the majority of which regularly receive
      requests for tissue for research purposes. Most requests come from academia and
      financial support to facilitate tissue release comes from a variety of sources. A
      range of practices were reported in relation to selection of the most appropriate
      sample to release, consent checking, costing and governance frameworks.
      CONCLUSIONS: This survey demonstrates wide variation in practice across the UK
      and identifies barriers to release of human tissue for clinical trial research.
      Until we can overcome these obstacles, patient samples will remain inaccessible
      to research. Therefore, this study highlights the urgent need for clear and
      coordinated national guidance on this issue.

PMID- 30275097
TI  - CD138/syndecan-1 in pancreatic solid and pseudopapillary neoplasms.

PMID- 30275095
TI  - Dried Blood Spot Technique-Based Liquid Chromatography-Tandem Mass Spectrometry
      Method as a Simple Alternative for Benznidazole Pharmacokinetic Assessment.
AB  - Chagas disease (CD) is recognized as one of the major neglected global tropical
      diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults,
      young infants, and newborns with CD. However, the pharmacokinetics (PK) of BNZ
      have been poorly evaluated in all age groups, with consequent gaps in knowledge
      about PK-pharmacodynamic relationships in CD. The purpose of this study was to
      develop and validate a bioanalytical method to quantify BNZ levels in small
      volume whole-blood samples collected as dried blood spots (DBS). The analysis was
      performed using high-performance liquid chromatography-positive electrospray
      tandem mass spectrometry. PK evaluation in healthy male volunteers was conducted
      to verify the correlation between DBS and plasma BNZ concentrations. The
      calibration curve was linear from 50 to 20,000 ng . ml-1 Intra- and interday
      precision and bias values were less than 14.87% (n = 9) and 9.81% (n = 27),
      respectively. The recovery rates ranged from 94 to 100% with no matrix effect.
      There was no hematocrit level effect in a range of 20 to 70%. The PK results
      obtained from DBS and plasma were comparable (r 2 = 0.8295) and equivalent to
      previously published information on BNZ. BNZ in DBS was stable at room
      temperature for more than one year. This article describes the first
      microsampling method for measuring BNZ levels in DBS that has the potential to
      facilitate broad implementation of PK in clinical trials involving adult and
      pediatric patients in remote areas and helps to address existing knowledge gaps
      in the treatment of CD.

PMID- 30275098
TI  - Setting up a service for a faecal immunochemical test for haemoglobin (FIT): a
      review of considerations, challenges and constraints.
AB  - Quantitative faecal immunochemical tests for haemoglobin (FIT) have now been
      advocated by the National Institute for Care and Health Excellence (NICE: DG30)
      to assist in the triage of patients presenting with symptoms that suggest a low
      risk of colorectal (bowel) cancer. The evidence is that FIT provides a good rule
      out test for significant bowel disease. However, a small number of cases will be
      missed, and robust safety-netting procedures are required to follow up some FIT
      negative patients. A range of diagnostic pathways are possible, and there is no
      best approach at present. Introduction of FIT requires careful consideration of
      the logistics of supply of devices and information to requesting sites and of
      transport to the laboratory. A number of FIT analytical systems are available.
      Three are documented as appropriate for use in assessment of patients with
      symptoms. However, preanalytical, analytical and postanalytical challenges
      remain. The methods have different specimen collection devices. The methods use
      polyclonal antibodies and there is no primary reference material or method to
      which FIT methods are standardised. Third-party internal quality control is
      lacking, and external quality assessment schemes have many difficulties in
      providing appropriate materials. Reporting of results should be done using ug
      Hb/g faeces units and with knowledge of the limit of detection and limit of
      quantitation of the analytical system used. FIT can be used successfully in an
      agreed diagnostic pathway, along with other clinical and laboratory information:
      this requires a multidisciplinary approach, providing opportunities for
      professionals in laboratory medicine involvement.

PMID- 30275100
TI  - Update on eighth edition American Joint Committee on Cancer classification for
      cutaneous melanoma and overview of potential pitfalls in histological examination
      of staging parameters.
AB  - Cutaneous melanoma causes most of the skin cancer deaths in the USA. Melanoma is
      the fifth most common cancer among men and the sixth most common cancer among
      women. The incidence of melanoma has risen sharply over the past three decades.
      In this review, which is informed by our extensive experience at a large cancer
      centre, we outline the key differences between the tumour, node and metastases
      staging criteria for cutaneous melanoma in the seventh and eighth editions of the
      AJCC Cancer Staging Manual We also offer advice on how to assess the
      histophenotypic parameters that are relevant for staging, with a special focus on
      avoiding potential pitfalls, and how to report all the prognostically and
      therapeutically relevant histophenotypic parameters. Correct assessment and
      reporting of these clinically relevant histophenotypic parameters is of outmost
      importance for practising pathologists because these parameters help treating
      clinicians select the most appropriate personalised treatment for patients in
      this era of promising targeted and immunotherapies.

PMID- 30275099
TI  - A real-world, comparative study of FDA-approved diagnostic assays PD-L1 IHC 28-8
      and 22C3 in lung cancer and other malignancies.
AB  - AIMS: At the time of analysis, two widely used, drug-specific, tumour-cell
      programmed death ligand 1 (PD-L1) assays were approved by the US Food and Drug
      Administration for anti-PD-1 therapies: the Dako PD-L1 immunohistochemistry (IHC)
      28-8 pharmDx assay and the Dako PD-L1 IHC 22C3 pharmDx assay. Given that the
      majority of current PD-L1 testing in US clinical practice is performed at
      commercial reference laboratories, we aimed to evaluate the concordance of the 28
      8 and 22C3 assays in a real-world setting. METHODS: Matched PD-L1 IHC 28-8 and
      22C3 results from routine assessment were obtained from 1930 patients, including
      412 confirmed to have lung cancer, submitted from hospitals in over 38 US
      states/territories. Biopsies were stained, reviewed and scored by
      trained/certified pathologists at a single cancer reference laboratory between
      2015 and 2017. Rate of concordance between assay findings was assessed by Bland
      Altman analysis; overall per cent agreement (OPA), positive per cent agreement
      and negative per cent agreement; and Cohen's kappa. RESULTS: PD-L1 IHC 28-8 and
      22C3 displayed strong correlation across all samples and in samples with a
      confirmed lung cancer diagnosis irrespective of biopsy site. The OPA was 97%-98%
      for all samples, depending on the expression level defining PD-L1 positivity. In
      the Bland-Altman analysis, the mean difference in percentage of tumour cells
      positively stained for PD-L1 between the paired assay findings was -0.80% for all
      samples and -0.93% in samples with a confirmed lung cancer diagnosis.
      CONCLUSIONS: These data, in conjunction with recent findings, support the
      analytical concordance of the PD-L1 IHC 28-8 and 22C3 assays for assessing per
      cent tumour-cell membrane PD-L1 expression.

PMID- 30275101
TI  - Molecules in cancer immunotherapy: benefits and side effects.
AB  - This mini review describes some of the key interactions between cancer cells and
      the immune system. This includes the concept of tumour cell immunosurveillance,
      mechanisms of immune evasion by tumour cells and some of the novel immunology
      based anticancer therapies that have recently been introduced. The latter are
      also set into the context of the enlarging spectrum of immunohistochemistry-based
      and molecular testing that can now be performed on formalin-fixed and paraffin
      embedded tissues for predicting response to both well-established and newly
      developed agents. The emerging field of cancer immunotherapy requires and
      encourages close working between cellular and molecular pathology and clinical
      cancer treatment, while providing new hope for patients with cancers that may not
      have responded to conventional oncological treatments.

PMID- 30275102
TI  - Apoptotic colopathy: a pragmatic approach to diagnosis.
AB  - 'Apoptotic colopathy' is an umbrella term signifying a pattern of injury where
      the gastrointestinal biopsy shows a colitic picture with apoptosis as the
      predominant histological feature. Although the entities within apoptotic
      colopathy share a common histological feature- 'apoptosis', there is a list of
      varied clinical differential diagnoses that produce this similar histological
      pattern of injury. These include graft-versus-host disease, drug-induced injury
      due to multiple drugs (in particular, mycophenolate mofetil, check point
      inhibitor therapy and some others), infections (particularly cytomegalovirus,
      adenovirus and some others), immune disorders and other miscellaneous causes.
      However, the management of these varied differentials is strikingly different,
      thus necessitating an algorithmic approach for accurate diagnosis and optimal
      patient management. A definitive diagnosis requires interpretation of varied
      histological findings in the appropriate clinical context including clinical
      history, drug history and laboratory findings. This review will focus on the
      histopathological findings of varied entities that can manifest as 'apoptotic
      colopathy' on assessment of colonic biopsies.

PMID- 30275103
TI  - Evidence-based medicine: clinicians are taught to say it but not taught to think
      it.

PMID- 30275104
TI  - Pathogenic and non-pathogenic Escherichia coli colonization and host inflammatory
      response in a defined microbiota mouse model.
AB  - Most Escherichia coli strains in the human intestine are harmless. However,
      enterohemorrhagic E coli (EHEC) is a foodborne pathogen that causes intestinal
      disease in humans. Conventionally reared (CONV) mice are inconsistent models for
      human infections with EHEC because they are often resistant to E coli
      colonization, in part due to their gastrointestinal (GI) microbiota. Although
      antibiotic manipulation of the mouse microbiota has been a common means to
      overcome colonization resistance, these models have limitations. Currently, there
      are no licensed treatments for clinical EHEC infections and, thus, new tools to
      study EHEC colonization need to be developed. Here, we used a defined microbiota
      mouse model, consisting of the altered Schaedler flora (ASF), to characterize
      intestinal colonization and compare host responses following colonization with
      EHEC strain 278F2 or non-pathogenic E coli strain MG1655. Significantly higher
      (P<0.05) levels of both strains were found in feces and cecal and colonic
      contents of C3H/HeN ASF compared to C3H/HeN CONV mice. GI inflammation was
      significantly elevated (P<0.05) in the cecum of EHEC 278F2-colonized compared to
      E. coli MG1655-colonized C3H/HeN ASF mice. In addition, EHEC 278F2 differentially
      modulated inflammatory-associated genes in colonic tissue of C3H/HeN ASF mice
      compared to E. coli MG1655-colonized mice. This approach allowed for prolonged
      colonization of the murine GI tract by pathogenic and non-pathogenic E coli
      strains, and for evaluation of host inflammatory processes. Overall, this system
      can be used as a powerful tool for future studies to assess therapeutics, microbe
      microbe interactions, and strategies for preventing EHEC infections.

PMID- 30275105
TI  - Structural insight into microtubule stabilization and kinesin inhibition by Tau
      family MAPs.
AB  - The Tau family microtubule-associated proteins (MAPs) promote microtubule
      stabilization and regulate microtubule-based motility. They share the C-terminal
      microtubule-binding domain, which includes three to five tubulin-binding repeats.
      Different numbers of repeats formed by alternative splicing have distinct effects
      on the activities of these proteins, and the distribution of these variants
      regulates fundamental physiological phenomena in cells. In this study, using cryo
      EM, we visualized the MAP4 microtubule complex with the molecular motor kinesin
      1. MAP4 bound to the C-terminal domains of tubulins along the protofilaments
      stabilizes the longitudinal contacts of the microtubule. The strongest bond of
      MAP4 was found around the intertubulin-dimer interface such that MAP4 coexists on
      the microtubule with kinesin-1 bound to the intratubulin-dimer interface as well.
      MAP4, consisting of five repeats, further folds and accumulates above the
      intertubulin-dimer interface, interfering with kinesin-1 movement. Therefore,
      these cryo-EM studies reveal new insight into the structural basis of microtubule
      stabilization and inhibition of kinesin motility by the Tau family MAPs.

PMID- 30275106
TI  - Legionella remodels the plasma membrane-derived vacuole by utilizing exocyst
      components as tethers.
AB  - During the initial stage of infection, Legionella pneumophila secretes effectors
      that promote the fusion of endoplasmic reticulum (ER)-derived vesicles with the
      Legionella-containing vacuole (LCV). This fusion leads to a remodeling of the
      plasma membrane (PM)-derived LCV into a specialized ER-like compartment that
      supports bacterial replication. Although the effector DrrA has been shown to
      activate the small GTPase Rab1, it remains unclear how DrrA promotes the
      tethering of host vesicles with the LCV. Here, we show that Sec5, Sec15, and
      perhaps Sec6, which are subunits of the exocyst that functions in the tethering
      of exocytic vesicles with the PM, are required for DrrA-mediated, ER-derived
      vesicle recruitment to the PM-derived LCV. These exocyst components were found to
      interact specifically with a complex containing DrrA, and the loss of Sec5 or
      Sec15 significantly suppressed the recruitment of ER-derived vesicles to the LCV
      and inhibited intracellular replication of Legionella Importantly, Sec15 is
      recruited to the LCV, and Rab1 activation is necessary for this recruitment.

PMID- 30275107
TI  - Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo.
AB  - Pulsed actomyosin contractility underlies diverse modes of tissue morphogenesis,
      but the underlying mechanisms remain poorly understood. Here, we combined
      quantitative imaging with genetic perturbations to identify a core mechanism for
      pulsed contractility in early Caenorhabditis elegans embryos. We show that pulsed
      accumulation of actomyosin is governed by local control of assembly and
      disassembly downstream of RhoA. Pulsed activation and inactivation of RhoA
      precede, respectively, the accumulation and disappearance of actomyosin and
      persist in the absence of Myosin II. We find that fast (likely indirect)
      autoactivation of RhoA drives pulse initiation, while delayed, F-actin-dependent
      accumulation of the RhoA GTPase-activating proteins RGA-3/4 provides negative
      feedback to terminate each pulse. A mathematical model, constrained by our data,
      suggests that this combination of feedbacks is tuned to generate locally
      excitable RhoA dynamics. We propose that excitable RhoA dynamics are a common
      driver for pulsed contractility that can be tuned or coupled differently to
      actomyosin dynamics to produce a diversity of morphogenetic outcomes.

PMID- 30275109
TI  - Bifunctional PD-1 * alphaCD3 * alphaCD33 fusion protein reverses adaptive immune
      escape in acute myeloid leukemia.
AB  - The CD33-targeting bispecific T-cell engager (BiTE) AMG 330 proved to be highly
      efficient in mediating cytolysis of acute myeloid leukemia (AML) cells in vitro
      and in mouse models. Yet, T-cell activation is correlated with upregulation of
      programmed cell death-ligand 1 (PD-L1) and other inhibitory checkpoints on AML
      cells that confer adaptive immune resistance. PD-1 and PD-L1 blocking agents may
      counteract T-cell dysfunction, however, at the expense of broadly distributed
      immune-related adverse events (irAEs). We developed a bifunctional checkpoint
      inhibitory T cell-engaging (CiTE) antibody that combines T-cell redirection to
      CD33 on AML cells with locally restricted immune checkpoint blockade. This is
      accomplished by fusing the extracellular domain of PD-1 (PD-1ex), which naturally
      holds a low affinity to PD-L1, to an alphaCD3.alphaCD33 BiTE-like scaffold. By a
      synergistic effect of checkpoint blockade and avidity-dependent binding, the PD
      1ex attachment increases T-cell activation (3.3-fold elevation of interferon
      gamma) and leads to efficient and highly selective cytotoxicity against CD33+PD
      L1+ cell lines (50% effective concentration = 2.3-26.9 pM) as well as patient
      derived AML cells (n = 8). In a murine xenograft model, the CiTE induces complete
      AML eradication without initial signs of irAEs as measured by body weight loss.
      We conclude that our molecule preferentially targets AML cells, whereas high
      affinity blockers, such as clinically approved anticancer agents, also address PD
      L1+ non-AML cells. By combining the high efficacy of T-cell engagers with immune
      checkpoint blockade in a single molecule, we expect to minimize irAEs associated
      with the systemic application of immune checkpoint inhibitors and suggest high
      therapeutic potential, particularly for patients with relapsed/ refractory AML.

PMID- 30275111
TI  - NHS agrees to pay millions to woman left paralysed by TB meningitis.

PMID- 30275108
TI  - Bidirectional intraflagellar transport is restricted to two sets of microtubule
      doublets in the trypanosome flagellum.
AB  - Intraflagellar transport (IFT) is the rapid bidirectional movement of large
      protein complexes driven by kinesin and dynein motors along microtubule doublets
      of cilia and flagella. In this study, we used a combination of high-resolution
      electron and light microscopy to investigate how and where these IFT trains move
      within the flagellum of the protist Trypanosoma brucei Focused ion beam scanning
      electron microscopy (FIB-SEM) analysis of trypanosomes showed that trains are
      found almost exclusively along two sets of doublets (3-4 and 7-8) and distribute
      in two categories according to their length. High-resolution live imaging of
      cells expressing mNeonGreen::IFT81 or GFP::IFT52 revealed for the first time IFT
      trafficking on two parallel lines within the flagellum. Anterograde and
      retrograde IFT occurs on each of these lines. At the distal end, a large
      individual anterograde IFT train is converted in several smaller retrograde
      trains in the space of 3-4 s while remaining on the same side of the axoneme.

PMID- 30275112
TI  - The biobank consent debate: Why 'meta-consent' is not the solution?
AB  - Over the past couple of decades, there has been an ongoing, often fierce, debate
      about the ethics of biobank participation. One central element of that debate has
      concerned the nature of informed consent, must specific reconsent be gained for
      each new use, or user, or is broad consent ethically adequate? Recently, Thomas
      Ploug and Soren Holm have developed an alternative to both specific and broad
      consent: what they call a meta-consent framework. On a meta-consent framework,
      participants can choose the type of consent framework they require, for different
      kinds of use, different types of user and so on. Meta-consent involves a
      distinctive kind of design of the consent process. Here it is argued, first, that
      although a meta-consent framework does not wrong participants, Ploug and Holm
      understate the likely costs and burdens of such a framework, so there are good
      practical reasons not to offer it. Second, although Ploug and Holm allude to some
      ethical considerations that might seem to ground an ethical argument for
      providing meta-consent, they do not offer any sound argument, and it does not
      wrong participants in any way to fail to offer them the opportunity to design
      their own consent process.

PMID- 30275110
TI  - A synthesis approach of mouse studies to identify genes and proteins in arterial
      thrombosis and bleeding.
AB  - Antithrombotic therapies reduce cardiovascular diseases by preventing arterial
      thrombosis and thromboembolism, but at expense of increased bleeding risks.
      Arterial thrombosis studies using genetically modified mice have been invaluable
      for identification of new molecular targets. Because of low sample sizes and
      heterogeneity in approaches or methodologies, a formal meta-analysis to compare
      studies of mice with single gene defects encountered major limitations. To
      overcome these, we developed a novel synthesis approach to quantitatively scale
      1514 published studies of arterial thrombus formation (in vivo and in vitro),
      thromboembolism and tail bleeding of genetically modified mice. Using a newly
      defined consistency parameter (CP), indicating the strength of published data,
      comparisons were made of 431 mouse genes, of which 17 consistently contributed to
      thrombus formation without affecting hemostasis. Ranking analysis indicated high
      correlations between collagen-dependent thrombosis models in vivo (FeCl3 injury
      or ligation/compression) and in vitro. Integration of scores and CP values
      resulted in a network of protein interactions in thrombosis and hemostasis
      (PITH), which was combined with databases of genetically linked human bleeding
      and thrombotic disorders. The network contained 2,946 nodes linked to modifying
      genes of thrombus formation, mostly with expression in megakaryocytes. Reactome
      pathway analysis and network characteristics revealed multiple novel genes with
      potential contribution to thrombosis/hemostasis. Studies with additional knockout
      mice revealed that 4/8 (Apoe, Fpr2, Ifnar1, Vps13a) new genes were modifying in
      thrombus formation. The PITH network further: (i) revealed a high similarity of
      murine and human hemostatic and thrombotic processes, and (ii) identified
      multiple new candidate proteins regulating these processes.

PMID- 30275113
TI  - Candida auris outbreak was linked to reusable axillary temperature probes, study
      finds.

PMID- 30275115
TI  - Dietary Heterocyclic Amine Intake and Colorectal Adenoma Risk: A Systematic
      Review and Meta-Analysis.
AB  - BACKGROUND: Heterocyclic amines (HCAs) are potent carcinogenic substances formed
      in meat. Due to their mutagenic activity, they may increase the risk of
      colorectal adenomas (CRA), which are precursors of colorectal cancer (CRC), one
      of the most prevalent cancers worldwide. The aim of this meta-analysis was to
      synthesize the knowledge about the intake of HCAs and its associations with CRA.
      METHODS: We conducted a systematic search in PubMed and EMBASE. We used odds
      ratio (OR) (or relative risks, RR) from every reported intake and compared the
      highest versus lowest level of dietary HCAs. In addition, we assessed a dose
      response relationship. RESULTS: Twelve studies on HCA intake and risk of CRA were
      included in our analysis. We observed a significant association when comparing
      top versus bottom intake category of 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP) (OR= 1.20, 95% CI=1.12 to 1.29), 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx) (OR=1.20; 95% CI=1.08 to 1.34), 2-
      amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) (OR=1.16; 95% CI=1.05 to
      1.27), benzo(a)pyrene (BaP) (OR=1.15; 95% CI=1.04 to 1.27) and mutagenicity index
      (OR=1.22;95% CI=1.06 to 1.41). Furthermore, we observed a significant dose
      response effect for PhIP, MeIQx and mutagenicity index. CONCLUSION: This meta
      analysis suggests that there is a positive association of HCAs, BaP, mutagenicity
      index with risk of CRA. Additionally, our dose-response analyses showed an
      increased risk for CRA in the case of PhIP, MeIQx and mutagenicity index. IMPACT:
      This study provides evidence for a positive association between the dietary
      intake of meat mutagens and CRA risk.

PMID- 30275114
TI  - The influence of pre-diagnosis alcohol consumption and the polymorphisms of
      ethanol metabolizing genes on the survival of head and neck cancer patients.
AB  - BACKGROUND: Although alcohol drinking is an established risk factor of head and
      neck cancer (HNC), less is known about its role in the prognosis of HNC. The
      current study investigated the association between pre-treatment alcohol
      consumption and the overall survival (OS) of HNC patients. METHODS: Cox
      proportional hazards models were performed to evaluate the association between
      pre-diagnosis alcohol drinking and the OS of HNC patients. In addition, the
      influence of the polymorphisms of two ethanol metabolizing genes, ADH1B and
      ALDH2, on this relationship was also evaluated. RESULTS: The results showed a
      significant positive dose-response relationship between pre-diagnosis alcohol use
      and worse OS of HNC patients. This association was more significant for
      oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer than for oral
      cancer. The association between alcohol use and the poorer OS of HNC patients was
      mainly through its association with a higher stage of HNC at diagnosis. The worst
      OS associated with alcohol use was observed among HNC patients with the fast
      ADH1B and the slow/non-functional ALDH2 genotype combination. CONCLUSIONS: Our
      analysis showed a significant positive dose-response relationship between pre
      diagnosis alcohol use and a worse OS of HNC. This association was mainly due to
      the higher stage of HNC among alcohol drinkers. In addition, the polymorphisms of
      the ethanol metabolizing gene, ADH1B and ALDH2, modified the relationship between
      pre-diagnosis alcohol use and the OS of HNC patients. IMPACT: Pre-diagnosis
      alcohol use may be a prognostic indicator of HNC.

PMID- 30275116
TI  - Multilevel regression for small-area estimation of mammography use in the United
      States, 2014.
AB  - BACKGROUND: The US Preventive Services Task Force recommends biennial screening
      mammography for average-risk women aged 50 to 74 years. County-level information
      on population measures of mammography use can inform targeted intervention to
      reduce geographic disparities in mammography use. County-level estimates for
      mammography use nationwide are rarely presented. METHODS: We used data from the
      2014 Behavioral Risk Factor Surveillance System (BRFSS) (n=130,289 women), linked
      it to the American Community Survey poverty data, and fitted multilevel logistic
      regression models with two outcomes: mammography within the past 2 years (up-to
      date); and most recent mammography 5 or more years ago or never (rarely/never).
      We post-stratified the data with US Census population counts to run Monte Carlo
      simulations. We generated county-level estimates nationally and by urban-rural
      county classifications. County-level prevalence estimates were aggregated into
      state and national estimates. We validated internal consistency between our model
      based state-specific estimates and urban-rural estimates with BRFSS direct
      estimates using Spearman correlation coefficients and mean absolute differences.
      RESULTS: Correlation coefficients were 0.94 or larger. Mean absolute differences
      for the 2 outcomes ranged from 0.79 to 1.03. Although 78.45% (95% CI: 77.95%
      ?78.92%) of women nationally were up-to-date with mammography, more than half of
      the states had counties with >15% of women rarely/never using a mammogram, many
      in rural areas. CONCLUSIONS: We provided estimates for all U.S. counties and
      identified marked variations in mammography use. Many states and counties were
      far from the 2020 target (81.1%). IMPACT: Our results suggest a need for planning
      and resource allocation on a local level to increase mammography uptake.

PMID- 30275117
TI  - Erratum: Lipid-transfer proteins rectify inter-organelle flux and accurately
      deliver lipids at membrane contact sites.

PMID- 30275118
TI  - Erratum: Flipping the cyclooxygenase (Ptgs) genes reveals isoform-specific
      compensatory functions.

PMID- 30275119
TI  - Regional Differences in Human Intestinal Drug Metabolism.
AB  - The intestines are key for the absorption of nutrients and water as well as drug
      metabolism, and it is well known that there are clear differences in the
      expression profile of drug metabolism enzymes along the intestinal tract. Yet
      only a few studies have thoroughly investigated regional differences in human
      intestinal drug metabolism. In this study, we evaluated phase I and phase II
      metabolism in matched human ileum and colon precision-cut intestinal slices
      (PCIS). To this end, human PCIS were incubated for 3 hours with testosterone and
      7-hydroxycoumarin (7-HC) to examine phase I and phase II metabolism,
      respectively. Metabolite formation was assessed by high-performance liquid
      chromatography analysis. Our results demonstrated that androstenedione, 6beta
      hydroxytestosterone, 2beta-hydroxytestosterone, and 7-HC sulfate were
      predominantly formed in the ileum, while 15alpha-hydroxytestosterone and 7-HC
      glucuronide were mainly produced in the colon. Moreover, we also observed sex
      differences in phase II metabolite formation, which appeared to be higher in men
      compared with women. Taken together, we demonstrated that phase I metabolism
      predominantly occurs in ileum PCIS, while phase II metabolism mostly takes place
      in colon PCIS. Moreover, we revealed that human PCIS can be used to study both
      regional and sex differences in intestinal metabolism.

PMID- 30275121
TI  - What's happening in Innovations in Care Delivery.

PMID- 30275120
TI  - What's happening in Neurology (r).

PMID- 30275122
TI  - Destructive craniovertebral junction tuberculosis and antituberculosis treatment.

PMID- 30275123
TI  - Opinion and Special Articles: Challenges and opportunities in defining career
      identity in academic neurology.

PMID- 30275124
TI  - Editors' note: Peak perihemorrhagic edema correlates with functional outcome in
      intracerebral hemorrhage.

PMID- 30275125
TI  - Reader response: Peak perihemorrhagic edema correlates with functional outcome in
      intracerebral hemorrhage.

PMID- 30275126
TI  - Author response: Peak perihemorrhagic edema correlates with functional outcome in
      intracerebral hemorrhage.

PMID- 30275128
TI  - Author response: Peak perihemorrhagic edema correlates with functional outcome in
      intracerebral hemorrhage.

PMID- 30275127
TI  - Reader response: Peak perihemorrhagic edema correlates with functional outcome in
      intracerebral hemorrhage.

PMID- 30275129
TI  - Clinical Reasoning: Rapidly progressive dementia in a patient with HIV after an
      exotic journey.

PMID- 30275130
TI  - Pearls & Oy-sters: Pembrolizumab-induced myasthenia gravis.

PMID- 30275131
TI  - Teaching NeuroImages: Distinctive imaging in a paucisymptomatic child with
      leukodystrophy.

PMID- 30275133
TI  - Simply Stated: Harassment and Gender Bias Are Unacceptable.

PMID- 30275132
TI  - Aspergillus and progression of lung disease in children with cystic fibrosis.
AB  - BACKGROUND: The impact of Aspergillus on lung disease in young children with
      cystic fibrosis is uncertain. AIMS: To determine if positive respiratory cultures
      of Aspergillus species are associated with: (1) increased structural lung injury
      at age 5 years; (2) accelerated lung function decline between ages 5 years and 14
      years and (3) to identify explanatory variables. METHODS: A cross-sectional
      analysis of association between Aspergillus positive bronchoalveolar lavage (BAL)
      cultures and chest high-resolution CT (HRCT) scan findings at age 5 years in
      subjects from the Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL)
      study was performed. A non-linear mixed-effects disease progression model was
      developed using FEV1% predicted measurements at age 5 years from the ACFBAL study
      and at ages 6-14 years for these subjects from the Australian Cystic Fibrosis
      Data Registry. RESULTS: Positive Aspergillus BAL cultures at age 5 years were
      significantly associated with increased HRCT scores for air trapping (OR 5.53,
      95% CI 2.35 to 10.82). However, positive Aspergillus cultures were not associated
      with either FEV1% predicted at age 5 years or FEV1% predicted by age following
      adjustment for body mass index z-score and hospitalisation secondary to pulmonary
      exacerbations. Lung function demonstrated a non-linear decline in this
      population. CONCLUSION: In children with cystic fibrosis, positive Aspergillus
      BAL cultures at age 5 years were associated contemporaneously with air trapping
      but not bronchiectasis. However, no association was observed between positive
      Aspergillus BAL cultures on FEV1% predicted at age 5 years or with lung function
      decline between ages 5 years and 14 years.

PMID- 30275134
TI  - Maximum Recommended Doses of Dental Local Anesthetics.

PMID- 30275135
TI  - Advancing Dental Education in the 21st Century: Developing the Phase 2 Strategic
      Analysis and Recommendations.

PMID- 30275136
TI  - An International Survey of Female Dental Students' Perceptions About Gender Bias
      and Sexual Misconduct at Four Dental Schools.
AB  - As women enter the dental profession in increasing numbers in North America and
      around the world, the questions of how they perceive their environment and what
      kind of barriers they face are important subjects to be addressed. The aim of
      this study was to assess and compare women dental students' perceptions of bias
      in their environment and experiences of sexual misconduct at one dental school in
      each of four countries. In spring 2017, 1,293 female students at four dental
      schools in the U.S., Bulgaria, Brazil, and India were invited to participate in a
      24-item survey developed by researchers from the four countries; 990 students
      responded (response rate 76.6%). The overall majority of the respondents reported
      thinking the admissions process at their school was fair (79.7%); but a fifth of
      U.S. and Brazilian students perceived their school was not fully embracing of
      females, with most Bulgarian students agreeing (87.2%) and all Indian students
      disagreeing. Most respondents overall perceived that male faculty members did not
      favor male students (79.5%) and did not think there was discrimination against
      female students by faculty (87.1%), but half of the U.S. respondents reported
      feeling discriminated against by both male faculty and male students. When the
      responses "I've been verbally harassed" and "I've been somewhat verbally
      harassed" were combined, 10.1% of the U.S. respondents reported verbal
      harassment, compared to 20% of Brazilian, 15% of Bulgarian, and 2% of Indian
      respondents. When the responses "I've been sexually assaulted" and "I've been
      somewhat sexually assaulted" were combined, 6% of U.S. respondents reported being
      sexually assaulted, compared to 6.2% of Brazilian, 2.5% of Bulgarian, and none of
      the Indian respondents. Almost half (46.9%) of these students overall perceived
      their school was not or only somewhat vigilant about issues of sexual misconduct,
      and only 54% said they would feel comfortable or very comfortable reporting
      misconduct. These results suggest that academic dental institutions in all four
      countries need improvements to make their environments more equitable and free of
      bias and sexual misconduct.

PMID- 30275137
TI  - Oral Health and Dental Students' Perceptions of Their Clinical Learning
      Environment: A Focus Group Study.
AB  - Creating an optimal clinical learning environment poses a challenge to health
      professions educators. To evaluate and improve the clinical learning environment,
      it is necessary to understand students' experiences of their environment and the
      factors they perceive as having an impact on their learning. The aim of this
      explorative qualitative study was to examine University of Otago Faculty of
      Dentistry students' perceptions of their clinical learning environment to gain
      insights into how learning outcomes could be enhanced. In 2015, all approximately
      600 students at all levels of the Bachelor of Oral Health and Bachelor of Dental
      Surgery degrees at the University of Otago, Dunedin, New Zealand, were invited to
      participate in focus groups. Focus groups facilitated by the faculty education
      research fellow and another researcher employed for the project were conducted
      during the second half of the academic year. Transcribed data were analyzed using
      a general inductive approach. Twenty-one students from all levels of the two
      programs attended one of six confidential focus groups. Three broad themes were
      evident in the results from all groups: feedback processes, assessments and
      grading, and tutor interactions. In the focus groups, students expressed
      dissatisfaction regarding current feedback practices, types of feedback to
      benefit learning, consistency in the grading system, and impact of different
      educators' teaching styles on learning. These results indicated a need for
      further research and curricular efforts to promote good student-teacher
      relationships in the clinical learning environment, which are paramount for
      creating an optimal teaching and learning environment and enhancing student
      outcomes.

PMID- 30275138
TI  - Comparison of Dental Students' Self-Evaluation and Faculty Evaluation of
      Communication Skills During a Standardized Patient Exercise.
AB  - The aims of this retrospective study, conducted in 2017, were to explore dental
      students' perceptions of their first standardized patient encounters and to
      assess the relationship between students' self-evaluation and faculty members'
      evaluation of students' communication skills in those encounters. Data from a
      simulation training laboratory at one U.S. dental school were obtained for all 46
      second-year students, who had a standardized patient communication learning
      session. The students had completed self-evaluations before and after a
      debriefing with a clinical psychology and/or social work faculty member and three
      or four student peers. The faculty members had also completed evaluations of the
      students' communications skills. The results showed that the students found the
      standardized patient encounter helpful. The students rated "making an
      introduction" most positively. Students had a weighted Kappa agreement of 0.22
      (p=0.024) with the faculty evaluations on their post-debriefing evaluation of
      overall communication skills, which was within the 0.21-0.40 range of fair
      agreement. This study found that, during their first standardized patient
      simulation exercise, the second-year students rated their overall communication
      skills in fair agreement with the faculty member after debriefing.

PMID- 30275139
TI  - Can Noncognitive Components of Admissions Data Predict Dental Student Performance
      and Postdoctoral Program Placement?
AB  - The aim of this retrospective cohort study was to evaluate whether the
      noncognitive factors of the dental student application, including undergraduate
      major and interview score, predicted success in the predoctoral program and
      placement in postdoctoral programs. The study population consisted of 169
      students in the Harvard School of Dental Medicine DMD graduating Classes of 2012
      through 2016. Noncognitive factors in the dental application, including letters
      of recommendation, extracurricular activities, undergraduate major, and dental
      school admission interview performance, were collected for the study population.
      Groups were analyzed for differences among undergraduate majors and any
      association between postgraduate placement and dental school performance. Dental
      school performance measures were grades obtained in the third and fourth years in
      a combination of preclinical and clinical course assessments. The results showed
      that neither interview score nor undergraduate major was significantly associated
      with dental school performance or postdoctoral program placement. There was a non
      significant association between interview score and performance in the course
      Treatment of Active Disease. These results suggest that noncognitive factors of
      the dental school application offered low yield to predicting predoctoral student
      performance and residency placements, with interview performance possibly
      outweighing undergraduate major in selection of successful predoctoral
      candidates.

PMID- 30275140
TI  - Preclinical Local Anesthesia Education in Dental Schools: A Systematic Review.
AB  - The aim of this systematic review was to evaluate the published literature on
      current educational techniques used to teach local anesthesia administration in
      U.S. dental schools to determine the methods by which potential complications may
      be minimized and efficacy maximized. A PubMed search was performed in June 2017
      on the following terms: (local anesthesia, education, dental) AND (Humans[Mesh]).
      Out of 136 articles identified, 13 met the study criteria and were included for
      review. Of those, the nine with outcome measures were included in the qualitative
      synthesis. With a quality assessment tool designed for this study, the quality of
      each included article was assessed independently by three of the authors. Three
      main pedagogies were identified: didactic instruction based on textbooks and
      lectures, student-to-student injections, and use of anatomic models. However, the
      effects of these pedagogies on local anesthesia administration efficacy, patient
      satisfaction, and student confidence in administering local anesthesia were
      largely not assessed in these studies. Quality assessment of the reviewed
      articles yielded a mean score of 62% (range 44-83%) for the observational studies
      and a mean score of 56% (range 47-63%) for the interventional studies. Due to the
      heterogeneity of the studies assessed, no meta-analysis could be performed. While
      the experimental and observational studies reviewed provided some insight into
      the efficacy of current educational techniques, they had numerous methodological
      inconsistencies. The inconsistency of the available evidence made it difficult to
      make fully informed curriculum recommendations based on the existing literature.

PMID- 30275141
TI  - Mind the Gap: A Systematic Review of Implementation of Screening for
      Psychological Comorbidity in Dental and Dental Hygiene Education.
AB  - The biopsychosocial model is advocated as part of a more comprehensive approach
      in both medicine and dentistry. However, dentists have not traditionally been
      taught psychosocial screening as part of their predoctoral education. The aim of
      this systematic review was to provide an overview of published studies on the
      implementation of screening for psychological comorbidity in dental and dental
      hygiene education. The term "psychological comorbidity" refers to the degree of
      coexisting anxiety, depression, or other mental health problems in a patient
      presenting with a physical condition. The review followed a protocol registered
      in PROSPERO (CRD42016054083) and was carried out in accordance with the PRISMA
      guidelines. The methodological quality of the included studies was assessed using
      a ten-item tool developed for medical education. The electronic search in PubMed,
      Scopus, and PsycINFO from the inception of each database until December 31, 2016,
      together with a hand search, identified 1,777 articles. After abstracts were
      screened, 52 articles were reviewed in full text applying inclusion and exclusion
      criteria; four articles remained for the qualitative synthesis. Generally, the
      reported data on specific methods or instruments used for psychological screening
      were limited. Only one of the included articles utilized a validated screening
      tool. The results of this systematic review show that published data on the
      implementation of psychological patient assessment in dental and dental hygiene
      education are limited. To address this gap, the authors recommend short screening
      tools such as the Graded Chronic Pain Scale and the Patient Health Questionnaire
      for Depression and Anxiety. Educating dental and dental hygiene students about
      easy-to-use, reliable, and validated screening tools for assessing psychological
      comorbidity warrants more research attention and greater implementation in
      educational curricula.

PMID- 30275142
TI  - Dental Students' Performance in Detecting In Vitro Occlusal Carious Lesions Using
      ICDAS with E-Learning and Digital Learning Strategies.
AB  - The aim of this study was to assess the performance of dental students for
      detecting in vitro occlusal carious lesions using the International Caries
      Detection and Assessment System (ICDAS) with different learning strategies. A
      convenience sample of all 64 fourth-year dental students at a dental school in
      Brazil who had no previous experience with ICDAS was selected for the study in
      2015. First, students performed the in vitro examination of the occlusal surfaces
      of 80 teeth according to ICDAS. Two weeks later, students were randomly allocated
      to three groups: G1 (n=21), ICDAS e-learning; G2 (n=22), ICDAS e-learning +
      digital learning tool (DLT); G3 (n=21), no training (control group). All students
      reexamined the 80 teeth according to ICDAS two weeks later. Sensitivity,
      specificity, and area under the ROC curve (AUC) were calculated according to
      three thresholds. Of the 64 students, 59 completed all study phases, for a 92.2%
      participation rate. The intra-group comparison found significantly higher
      sensitivity and specificity values for G1 and G2 students. G3 students showed an
      increased sensitivity at the D2 threshold. G2 was the only training strategy that
      resulted in significant improvement for the AUC. In the comparison of groups at
      the same threshold, G1 showed higher specificity at D3 threshold (0.78) than G2
      (0.72) and G3 (0.73). Regarding sensitivity, G1 showed a lower value at D2 (0.91)
      threshold than G2 (0.94) and G3 (0.94). In this study, both training strategies
      (ICDAS e-learning and ICDAS e-learning + DLT) improved the performance of dental
      students for the in vitro detection of occlusal carious lesions, mainly when the
      association of methods was used.

PMID- 30275143
TI  - Evaluation of an Interprofessional Oral Health Assessment Activity in Advanced
      Practice Nursing Education.
AB  - The curriculum for nurse practitioner (NP) students often overlooks the
      assessment of the oral cavity. In recognition of this, the HEENT (head, eyes,
      ears, nose, and throat) assessment was expanded to HEENOT (head, ears, eyes,
      nose, oral, and throat) through integration of an interprofessional educational
      (IPE) activity developed for University of Colorado NP and dental students. The
      aim of this study was to assess NP students' perceptions of an IPE activity in
      which dental faculty and students taught NP students how to conduct an oral exam,
      recognize oral health pathology, and apply fluoride varnish. Afterwards, the NP
      students completed an evaluation survey focusing on their thoughts, comfort
      level, organization, and understanding of the activity. This IPE activity was
      repeated over four semesters from 2014 to 2017, and significant differences among
      the semesters were compared. All NP students in the four semesters participated
      in the activity and the survey: semester one N=25, semester two N=31, semester
      three N=43, and semester four N=25. In all semesters, NP students reported
      feeling more confident conducting oral health exams after completion of the IPE
      activity. Semester four students agreed more with the idea of interprofessional
      collaboration (OR: 0.103) and receiving educational information not learned
      elsewhere in the curriculum (OR: 0.134) compared to semester one students. Higher
      odds for the session being well organized and conducted in a suitable time were
      found for semester four compared to semester two (OR: 0.217). These comparisons
      reflect improvement in teaching methodologies over the four semesters and an
      overall increased confidence for NP students in performing an oral health
      assessment.

PMID- 30275144
TI  - Using Interprofessional Education to Promote Oral Health Literacy in a Faculty
      Student Collaborative Practice.
AB  - The aim of this study was to assess the oral health literacy knowledge gained by
      patients who are refugees, community members, and medical and nursing students
      after participating in an interprofessional education collaborative of students
      and faculty from the University of Texas Health San Antonio Schools of Dentistry,
      Medicine, and Nursing. In this faculty-student collaborative practice, all
      patients were triaged (including oral hygiene status and alcohol/tobacco use),
      and tailored treatment options were offered following assessment of their dental,
      medical, and social histories. The study was designed as a pre-post assessment of
      an educational intervention on oral health literacy. In the pretest, all groups
      were invited to respond to questionnaires assessing their knowledge of oral
      health. After participants engaged in oral hygiene instruction demonstrations and
      received information about an oral health literacy campaign, a posttest was
      conducted to assess knowledge gained. A total of 151 patients who were refugees,
      38 medical students, 34 nursing students, and 17 community/parish members
      voluntarily participated in this initiative. Each group had a significant
      increase in mean oral health literacy score from pre- to posttest: patients
      33.5%, community/parish members 22.3%, nursing students 20.8%, and medical
      students 13% (all p<0.0001). These results showed that the oral health literacy
      initiative helped increase all participants' oral health literacy and knowledge
      of preventive care.

PMID- 30275145
TI  - Design and Validation of a Basic Dental Psychomotor Skills Test for Novice Dental
      Students.
AB  - The aim of this study was to design and validate the Dental Psychomotor Skills
      (DePS) test as an instrument to assess dental students' psychomotor skills and to
      help educators adapt their academic practices to students' needs. The DePS test
      was created considering three of the main skills needed for dental study and
      practice. The dimensions measured in the test were Indirect Vision (IV) with 24
      items, Instructions Follow-Up (FI) with 17 items, and Accuracy (A) with six
      items; each item was assessed at two stations. Scores were obtained with detailed
      rubrics, assessed by the same evaluator at each station. A total of 237 first
      year dental students, in four cohorts from 2012 to 2015, and 16 dental faculty
      instructors were evaluated. The construct validity of the instrument was
      supported by the rigorous build of ten stages, and the discriminative validity
      was supported by the comparison of the student and faculty results. The overall
      mean scores were 245.5+/-2.09 in the student group and 280.6+/-4.217 in the
      faculty group (difference: 35.15+/-7.00; p<0.001). Internal consistency was
      assessed by analyzing responses for each dimension using Cronbach's alpha, a
      statistical measure of reliability. Overall, Cronbach's alpha was 0.909 for
      dental students and 0.773 for faculty instructors. These results suggest that the
      DePS test is a valid test that could be used as a reliable basic skill tool at
      the beginning of the dental program to assess the abilities of novice dental
      students, to recognize student qualities, and to identify individuals requiring
      additional training.

PMID- 30275147
TI  - Peer Education: Reviews of the Literature (PERLs).

PMID- 30275148
TI  - Snapshot of Dental Education.

PMID- 30275146
TI  - Assessment of Psychometric Properties of an Oral Health Care Measure of Cultural
      Competence Among Dental Students Using Rasch Partial Credit Model.
AB  - Reliability, validity, and feasibility of the only validated oral health care
      measure of cultural competence, the Knowledge, Efficacy, and Practices Instrument
      (KEPI), have been confirmed. However, the instrument's psychometric properties
      including item and person reliability, category response functioning, and scale
      targeting, as well as differential scale functioning for subgroups, have not yet
      been examined. The aim of this study was to test the psychometric properties of
      KEPI among dental students using Rasch Partial Credit Model to determine if this
      model provided broader valid information that cannot be demonstrated according to
      Classical Test Theory. A total 1,290 dental students in the first or final
      semester at four U.S. dental schools were invited to participate in the study in
      2016. Of those, 1,231 individuals completed the survey, for a 95.4% response
      rate. The participants were 613 males and 618 females and 889 non
      underrepresented minority (URM) and 342 URM students. The Rasch Partial Credit
      Model assessed the psychometric properties of KEPI's 20 items/three subscales.
      Differential scale functioning was found in the Culture-Centered Practice and
      Efficacy of Assessment subscales. Four items were endorsed differentially by
      gender; four items were endorsed differentially by URM/non-URM students. This
      study examined the psychometric properties of the KEPI using Rasch analysis to
      assess differential item functioning by dental student gender and race. The
      results provided valid evidence for the high internal reliability, measurement
      properties, and unidimensionality for the KEPI domains, ideal targeting, and well
      response category functioning, showing that the KEPI is a reliable instrument for
      measuring the subscales Knowledge of Diversity, Culture-Centered Practice skills,
      and Efficacy of Assessment for health care providers.

PMID- 30275149
TI  - Advancing Dental Education in the 21st Century: Phase 2 Report on Strategic
      Analysis and Recommendations.
AB  - In Phase 1 of the "Advancing Dental Education in the 21st Century" project,
      research was conducted and published on a number of serious challenges facing
      dental and allied dental education, both presently and projected to 2040. Those
      findings informed the strategic analysis and recommendations developed in Phase 2
      of the project. This report provides an overview of the Phase 2 conclusions and
      presents recommendations to address the challenges identified. The
      recommendations propose ways to educate a workforce prepared to meet the oral
      health needs of the population; develop a sustainable economic model that allows
      schools to meet their education, research, and service missions; make dental and
      allied dental education and practice an integral part of the larger health
      education and delivery systems; and keep dentistry advancing as a "learned"
      profession. This report begins with an Executive Summary and then presents the
      strategic analysis of challenges facing dental schools and allied dental programs
      and provides a brief explanation of the rationale for each recommendation. Two
      appendices are included with the report: the first summarizes discussions held at
      the national conference to consider the recommendations; and the second provides
      additional documentation of calculations used to estimate the number of new
      dental graduates needed in 2040.

PMID- 30275150
TI  - The Endogenous Lusitropic and Chronotropic Agent, B-Type Natriuretic Peptide,
      Limits Cardiac Troponin Release in Cancer Patients with an Early Impairment of
      Myocardial Relaxation Induced by Anthracyclines.
AB  - We have reported that cancer patients treated with anthracycline-based or
      nonanthracycline chemotherapy developed an early impairment of myocardial
      relaxation at echocardiography or persistent elevations of the cardiac hormone B
      type natriuretic peptide (BNP). Post-hoc pharmacologic analyses showed that BNP
      elevations were induced by impaired relaxation and caused positive lusitropic
      effects that maintained normal relaxation. High BNP levels and impaired
      relaxation were therefore characterized as mutually exclusive manifestations of
      diastolic dysfunction, but high BNP levels resulted in positive chronotropism and
      inappropriate tachycardia. Some patients developed increased circulating levels
      of cardiac troponin I isoform (cTnI), a marker of cardiomyocyte necrosis. Here we
      have characterized whether cTnI elevations correlated with diastolic dysfunction
      that manifested as impaired relaxation or a high level of BNP. The effects of
      high BNP levels on cTnI elevations were also characterized. We show that impaired
      relaxation or high BNP levels were significantly more frequent in patients with
      cTnI elevations. High BNP levels diminished the plasma peak and area under the
      curve of cTnI, but this result was accompanied by inappropriate tachycardia. cTnI
      elevations occurred only in patients treated with anthracyclines; moreover, the
      association of impaired relaxation or high BNP levels with cTnI elevations was
      significantly more frequent in doxorubicin-treated patients compared with
      patients treated with its analog, epirubicin. These findings describe cause-and
      effect relations between impaired relaxation and cardiomyocyte necrosis,
      illuminate the role of anthracycline analogs, denote that the beneficial effects
      of BNP in relieving impaired relaxation and cardiomyocyte necrosis are
      counterbalanced by inappropriate tachycardia. Patients showing troponin
      elevations and impaired relaxation or high BNP levels should be treated with
      lusitropic drugs that lack a positive chronotropism.

PMID- 30275152
TI  - Targeting Canine KIT Promoter by Candidate DNA G-Quadruplex Ligands.
AB  - G-quadruplexes (G4) are nucleic acid secondary structures frequently assumed by G
      rich sequences located mostly at telomeres and proto-oncogenes promoters.
      Recently, we identified, in canine KIT (v-kit Hardy-Zuckerman 4 feline sarcoma
      viral oncogene homolog) promoter, two G-rich sequences able to fold into G4:
      d_kit1 and d_kit2_A16. In this study, an anthraquinone (AQ1) and an anthracene
      derivative (AN6), known to stabilize the G4 structures of the corresponding human
      h_kit1 and h_kit2, were tested on the canine G4 and in two canine mast cell tumor
      (MCT) cell lines (C2 and NI-1) to verify their capability to down-regulate KIT
      expression. The cytotoxicity of AQ1 and AN6 was determined using the Alamar Blue
      test; also the constitutive expression of KIT and other proto-oncogenes
      containing G4 structures in their promoter (BCL2, VEGFalpha, VEGFR2, KRAS, and
      TERT) was assessed by quantitative real-time polymerase chain reaction (qRT-PCR).
      Then the time- and dose-dependent effects of both ligands on target gene
      expression were assessed by qRT-PCR. All target genes were constitutively
      expressed up to 96 hours of culture. Both ligands decreased KIT mRNA levels and c
      kit protein amount, and AN6 was comparatively fairly more effective. DNA
      interaction studies and a dual-luciferase gene reporter assay performed on a
      noncancerous canine cell line (Madin-Darby Canine Kidney cells) proved that this
      down-regulation was the result of the interaction of AN6 with KIT proximal
      promoter. Interestingly, our results only partially overlap with those previously
      obtained in human cell lines, where AQ1 was found as the most effective compound.
      These preliminary data might suggest AN6 as a promising candidate for the
      selective targeting of canine KIT-dependent tumors.

PMID- 30275154
TI  - Erratum for Salvetti et al., "Comparative Genomics of the Genus Lactobacillus
      Reveals Robust Phylogroups That Provide the Basis for Reclassification".

PMID- 30275151
TI  - Brain-Permeant and -Impermeant Inhibitors of Fatty Acid Amide Hydrolase Synergize
      with the Opioid Analgesic Morphine to Suppress Chemotherapy-Induced Neuropathic
      Nociception Without Enhancing Effects of Morphine on Gastrointestinal Transit.
AB  - Opioid-based therapies remain a mainstay for chronic pain management, but
      unwanted side effects limit therapeutic use. We compared efficacies of brain
      permeant and -impermeant inhibitors of fatty acid amide hydrolase (FAAH) in
      suppressing neuropathic pain induced by the chemotherapeutic agent paclitaxel.
      Paclitaxel produced mechanical and cold allodynia without altering nestlet
      shredding or marble burying behaviors. We compared FAAH inhibitors that differ in
      their ability to penetrate the central nervous system for antiallodynic efficacy,
      pharmacological specificity, and synergism with the opioid analgesic morphine.
      (3'-(aminocarbonyl)[1,1'-biphenyl]- 3-yl)-cyclohexylcarbamate (URB597), a brain
      permeant FAAH inhibitor, attenuated paclitaxel-induced allodynia via cannabinoid
      receptor 1 (CB1) and cannabinoid receptor 2 (CB2) mechanisms. URB937, a brain
      impermeant FAAH inhibitor, suppressed paclitaxel-induced allodynia through a CB1
      mechanism only. 5-[4-(4-cyano-1-butyn-1-yl)phenyl]-1-(2,4-dichlorophenyl)-N-(1,1
      dioxido-4-thiomorpholinyl)-4-methyl-1H-pyrazole-3-carboxamide (AM6545), a
      peripherally restricted CB1 antagonist, fully reversed the antiallodynic efficacy
      of N-cyclohexyl-carbamic acid, 3'-(aminocarbonyl)-6-hydroxy[1,1'- biphenyl]-3-yl
      ester (URB937) but only partially reversed that of URB597. Thus, URB937
      suppressed paclitaxel-induced allodynia through a mechanism that was dependent
      upon peripheral CB1 receptor activation only. Antiallodynic effects of both FAAH
      inhibitors were reversed by N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4
      dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251). Antiallodynic effects
      of URB597, but not URB937, were reversed by 6-iodo-2-methyl-1-[2-(4
      morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone (AM630).
      Isobolographic analysis revealed synergistic interactions between morphine and
      either URB597 or URB937 in reducing paclitaxel-induced allodynia. A leftward
      shift in the dose-response curve of morphine antinociception was observed when
      morphine was coadministered with either URB597 or URB937, consistent with
      morphine sparing. However, neither URB937 nor URB597 enhanced morphine-induced
      deficits in colonic transit. Thus, our findings suggest that FAAH inhibition may
      represent a therapeutic avenue to reduce the overall amount of opioid needed for
      treating neuropathic pain with potential to reduce unwanted side effects that
      accompany opioid administration.

PMID- 30275155
TI  - Biogeodynamics: bridging the gap between surface and deep Earth processes.
AB  - Life is sustained by a critical and not insubstantial set of elements, nearly all
      of which are contained within large rock reservoirs and cycled between Earth's
      surface and the mantle via subduction zone plate tectonics. Over geologic time
      scales, plate tectonics plays a critical role in recycling subducted bioactive
      elements lost to the mantle back to the ocean-biosphere system, via outgassing
      and volcanism. Biology additionally relies on tectonic processes to supply rock
      bound 'nutrients' to marine and terrestrial ecosystems via uplift and erosion.
      Thus, the development of modern-style plate tectonics and the generation of
      stable continents were key events in the evolution of the biosphere on Earth, and
      similar tectonic processes could be crucial for the development of habitability
      on exoplanets. Despite this vital 'biogeodynamic' connection, directly testing
      hypotheses about feedbacks between the deep Earth and the biosphere remains
      challenging. Here, I discuss potential avenues to bridge the biosphere-geosphere
      gap, focusing specifically on the global cycling and bioavailability of major
      nutrients (nitrogen and phosphorus) over geologic time scales.This article is
      part of a discussion meeting issue 'Earth dynamics and the development of plate
      tectonics'.

PMID- 30275156
TI  - Rates of generation and destruction of the continental crust: implications for
      continental growth.
AB  - Less than 25% of the volume of the juvenile continental crust preserved today is
      older than 3 Ga, there are no known rocks older than approximately 4 Ga, and yet
      a number of recent models of continental growth suggest that at least 60-80% of
      the present volume of the continental crust had been generated by 3 Ga. Such
      models require that large volumes of pre-3 Ga crust were destroyed and replaced
      by younger crust since the late Archaean. To address this issue, we evaluate the
      influence on the rock record of changing the rates of generation and destruction
      of the continental crust at different times in Earth's history. We adopted a box
      model approach in a numerical model constrained by the estimated volumes of
      continental crust at 3 Ga and the present day, and by the distribution of crust
      formation ages in the present-day crust. The data generated by the model suggest
      that new continental crust was generated continuously, but with a marked decrease
      in the net growth rate at approximately 3 Ga resulting in a temporary reduction
      in the volume of continental crust at that time. Destruction rates increased
      dramatically around 3 billion years ago, which may be linked to the widespread
      development of subduction zones. The volume of continental crust may have
      exceeded its present value by the mid/late Proterozoic. In this model, about 2.6
      2.3 times of the present volume of continental crust has been generated since
      Earth's formation, and approximately 1.6-1.3 times of this volume has been
      destroyed and recycled back into the mantle.This article is part of a discussion
      meeting issue 'Earth dynamics and the development of plate tectonics'.

PMID- 30275157
TI  - Geological archive of the onset of plate tectonics.
AB  - Plate tectonics, involving a globally linked system of lateral motion of rigid
      surface plates, is a characteristic feature of our planet, but estimates of how
      long it has been the modus operandi of lithospheric formation and interactions
      range from the Hadean to the Neoproterozoic. In this paper, we review
      sedimentary, igneous and metamorphic proxies along with palaeomagnetic data to
      infer both the development of rigid lithospheric plates and their independent
      relative motion, and conclude that significant changes in Earth behaviour
      occurred in the mid- to late Archaean, between 3.2 Ga and 2.5 Ga. These data
      include: sedimentary rock associations inferred to have accumulated in passive
      continental margin settings, marking the onset of sea-floor spreading; the oldest
      foreland basin deposits associated with lithospheric convergence; a change from
      thin, new continental crust of mafic composition to thicker crust of intermediate
      composition, increased crustal reworking and the emplacement of potassic and
      peraluminous granites, indicating stabilization of the lithosphere; replacement
      of dome and keel structures in granite-greenstone terranes, which relate to
      vertical tectonics, by linear thrust imbricated belts; the commencement of
      temporally paired systems of intermediate and high dT/dP gradients, with the
      former interpreted to represent subduction to collisional settings and the latter
      representing possible hinterland back-arc settings or ocean plateau environments.
      Palaeomagnetic data from the Kaapvaal and Pilbara cratons for the interval 2780
      2710 Ma and from the Superior, Kaapvaal and Kola-Karelia cratons for 2700-2440 Ma
      suggest significant relative movements. We consider these changes in the
      behaviour and character of the lithosphere to be consistent with a gestational
      transition from a non-plate tectonic mode, arguably with localized subduction, to
      the onset of sustained plate tectonics.This article is part of a discussion
      meeting issue 'Earth dynamics and the development of plate tectonics'.

PMID- 30275158
TI  - The evolution of plate tectonics.
AB  - To understand how plate tectonics became Earth's dominant mode of convection, we
      need to address three related problems. (i) What was Earth's tectonic regime
      before the present episode of plate tectonics began? (ii) Given the preceding
      tectonic regime, how did plate tectonics become established? (iii) When did the
      present episode of plate tectonics begin? The tripartite nature of the problem
      complicates solving it, but, when we have all three answers, the requisite
      consilience will provide greater confidence than if we only focus on the long
      standing question of when did plate tectonics begin? Earth probably experienced
      episodes of magma ocean, heat-pipe, and increasingly sluggish single lid
      magmatotectonism. In this effort we should consider all possible scenarios and
      lines of evidence. As we address these questions, we should acknowledge there
      were probably multiple episodes of plate tectonic and non-plate tectonic
      convective styles on Earth. Non-plate tectonic styles were probably dominated by
      'single lid tectonics' and this evolved as Earth cooled and its lithosphere
      thickened. Evidence from the rock record indicates that the modern episode of
      plate tectonics began in Neoproterozoic time. A Neoproterozoic transition from
      single lid to plate tectonics also explains kimberlite ages, the Neoproterozoic
      climate crisis and the Neoproterozoic acceleration of evolution.This article is
      part of a discussion meeting issue 'Earth dynamics and the development of plate
      tectonics'.

PMID- 30275159
TI  - Crustal evolution and mantle dynamics through Earth history.
AB  - Resolving the modes of mantle convection through Earth history, i.e. when plate
      tectonics started and what kind of mantle dynamics reigned before, is essential
      to the understanding of the evolution of the whole Earth system, because plate
      tectonics influences almost all aspects of modern geological processes. This is a
      challenging problem because plate tectonics continuously rejuvenates Earth's
      surface on a time scale of about 100 Myr, destroying evidence for its past
      operation. It thus becomes essential to exploit indirect evidence preserved in
      the buoyant continental crust, part of which has survived over billions of years.
      This contribution starts with an in-depth review of existing models for
      continental growth. Growth models proposed so far can be categorized into three
      types: crust-based, mantle-based and other less direct inferences, and the first
      two types are particularly important as their difference reflects the extent of
      crustal recycling, which can be related to subduction. Then, a theoretical basis
      for a change in the mode of mantle convection in the Precambrian is reviewed,
      along with a critical appraisal of some popular notions for early Earth dynamics.
      By combining available geological and geochemical observations with geodynamical
      considerations, a tentative hypothesis is presented for the evolution of mantle
      dynamics and its relation to surface environment; the early onset of plate
      tectonics and gradual mantle hydration are responsible not only for the formation
      of continental crust but also for its preservation as well as its emergence above
      sea level. Our current understanding of various material properties and
      elementary processes is still too premature to build a testable, quantitative
      model for this hypothesis, but such modelling efforts could potentially transform
      the nature of the data-starved early Earth research by quantifying the extent of
      preservation bias.This article is part of a discussion meeting issue 'Earth
      dynamics and the development of plate tectonics'.

PMID- 30275160
TI  - The dependence of planetary tectonics on mantle thermal state: applications to
      early Earth evolution.
AB  - For plate tectonics to operate on a planet, mantle convective forces must be
      capable of forming weak, localized shear zones in the lithosphere that act as
      plate boundaries. Otherwise, a planet's mantle will convect in a stagnant lid
      regime, where subduction and plate motions are absent. Thus, when and how plate
      tectonics initiated on the Earth is intrinsically tied to the ability of mantle
      convection to form plate boundaries; however, the physics behind this process are
      still uncertain. Most mantle convection models have employed a simple
      pseudoplastic model of the lithosphere, where the lithosphere 'fails' and
      develops a mobile lid when stresses in the lithosphere reach the prescribed yield
      stress. With pseudoplasticity high mantle temperatures and high rates of internal
      heating, conditions relevant for the early Earth, impede plate boundary formation
      by decreasing lithospheric stresses, and hence favour a stagnant lid for the
      early Earth. However, when a model for shear zone formation based on grain size
      reduction is used, early Earth thermal conditions do not favour a stagnant lid.
      While lithosphere stress drops with increasing mantle temperature or heat
      production rate, the deformational work, which drives grain size reduction,
      increases. Thus, the ability of convection to form weak plate boundaries is not
      impeded by early Earth thermal conditions. However, mantle thermal state does
      change the style of subduction and lithosphere mobility; high mantle temperatures
      lead to a more sluggish, drip-like style of subduction. This 'sluggish lid'
      convection may be able to explain many of the key observations of early Earth
      crust formation processes preserved in the geologic record. Moreover, this work
      highlights the importance of understanding the microphysics of plate boundary
      formation for assessing early Earth tectonics, as different plate boundary
      formation mechanisms are influenced by mantle thermal state in fundamentally
      different ways.This article is part of a discussion meeting issue 'Earth dynamics
      and the development of plate tectonics'.

PMID- 30275161
TI  - Global tectonic evolution of Venus, from exogenic to endogenic over time, and
      implications for early Earth processes.
AB  - Venus provides a rich arena in which to stretch one's tectonic imagination with
      respect to non-plate tectonic processes of heat transfer on an Earth-like planet.
      Venus is similar to Earth in density, size, inferred composition and heat budget.
      However, Venus' lack of plate tectonics and terrestrial surficial processes
      results in the preservation of a unique surface geologic record of non-plate
      tectonomagmatic processes. In this paper, I explore three global tectonic domains
      that represent changes in global conditions and tectonic regimes through time,
      divided respectively into temporal eras. Impactors played a prominent role in the
      ancient era, characterized by thin global lithosphere. The Artemis superstructure
      era highlights sublithospheric flow processes related to a uniquely large super
      plume. The fracture zone complex era, marked by broad zones of tectonomagmatic
      activity, witnessed coupled spreading and underthrusting, since arrested. These
      three tectonic regimes provide possible analogue models for terrestrial Archaean
      craton formation, continent formation without plate tectonics, and mechanisms
      underlying the emergence of plate tectonics. A bolide impact model for craton
      formation addresses the apparent paradox of both undepleted mantle and growth of
      Archaean crust, and recycling of significant Archaean crust to the mantle.This
      article is part of a discussion meeting issue 'Earth dynamics and the development
      of plate tectonics'.

PMID- 30275162
TI  - The inception of plate tectonics: a record of failure.
AB  - The development of plate tectonics from a pre-plate tectonics regime requires
      both the initiation of subduction and the development of nascent subduction zones
      into long-lived contiguous features. Subduction itself has been shown to be
      sensitive to system parameters such as thermal state and the specific rheology.
      While generally it has been shown that cold-interior high-Rayleigh-number
      convection (such as on the Earth today) favours plates and subduction, due to the
      ability of the interior stresses to couple with the lid, a given system may or
      may not have plate tectonics depending on its initial conditions. This has led to
      the idea that there is a strong history dependence to tectonic evolution-and the
      details of tectonic transitions, including whether they even occur, may depend on
      the early history of a planet. However, intrinsic convective stresses are not the
      only dynamic drivers of early planetary evolution. Early planetary geological
      evolution is dominated by volcanic processes and impacting. These have rarely
      been considered in thermal evolution models. Recent models exploring the details
      of plate tectonic initiation have explored the effect of strong thermal plumes or
      large impacts on surface tectonism, and found that these 'primary drivers' can
      initiate subduction, and, in some cases, over-ride the initial state of the
      planet. The corollary of this, of course, is that, in the absence of such ongoing
      drivers, existing or incipient subduction systems under early Earth conditions
      might fail. The only detailed planetary record we have of this development comes
      from Earth, and is restricted by the limited geological record of its earliest
      history. Many recent estimates have suggested an origin of plate tectonics at
      approximately 3.0 Ga, inferring a monotonically increasing transition from pre
      plates, through subduction initiation, to continuous subduction and a modern
      plate tectonic regime around that time. However, both numerical modelling and the
      geological record itself suggest a strong nonlinearity in the dynamics of the
      transition, and it has been noted that the early history of Archaean greenstone
      belts and trondhjemite-tonalite-granodiorite record many instances of failed
      subduction. Here, we explore the history of subduction failure on the early
      Earth, and couple these with insights from numerical models of the geodynamic
      regime at the time.This article is part of a discussion meeting issue 'Earth
      dynamics and the development of plate tectonics'.

PMID- 30275163
TI  - The diversity of tectonic modes and thoughts about transitions between them.
AB  - Plate tectonics is a particular mode of tectonic activity that characterizes the
      present-day Earth. It is directly linked to not only tectonic deformation but
      also magmatic/volcanic activity and all aspects of the rock cycle. Other
      terrestrial planets in our Solar System do not operate in a plate tectonic mode
      but do have volcanic constructs and signs of tectonic deformation. This indicates
      the existence of tectonic modes different from plate tectonics. This article
      discusses the defining features of plate tectonics and reviews the range of
      tectonic modes that have been proposed for terrestrial planets to date. A
      categorization of tectonic modes relates to the issue of when plate tectonics
      initiated on Earth as it provides insights into possible pre-plate tectonic
      behaviour. The final focus of this contribution relates to transitions between
      tectonic modes. Different transition scenarios are discussed. One follows classic
      ideas of regime transitions in which boundaries between tectonic modes are
      determined by the physical and chemical properties of a planet. The other
      considers the potential that variations in temporal evolution can introduce
      contingencies that have a significant effect on tectonic transitions. The latter
      scenario allows for the existence of multiple stable tectonic modes under the
      same physical/chemical conditions. The different transition potentials imply
      different interpretations regarding the type of variable that the tectonic mode
      of a planet represents. Under the classic regime transition view, the tectonic
      mode of a planet is a state variable (akin to temperature). Under the multiple
      stable modes view, the tectonic mode of a planet is a process variable. That is,
      something that flows through the system (akin to heat). The different
      implications that follow are discussed as they relate to the questions of when
      did plate tectonics initiate on Earth and why does Earth have plate
      tectonics.This article is part of a discussion meeting issue 'Earth dynamics and
      the development of plate tectonics'.

PMID- 30275164
TI  - Laboratory investigation of mechanisms for phase mixing in olivine +
      ferropericlase aggregates.
AB  - To investigate the role of grain boundary pinning and the mechanisms by which
      phase mixing occurs during deformation of polymineralic rocks, we conducted high
      strain torsion experiments on samples consisting of olivine plus 30 vol%
      ferropericlase. Experiments were performed in a gas-medium deformation apparatus
      at 1524 K and 300 MPa. Samples were deformed to outer radius shear strains of up
      to gamma(R) = 14.1. The value of the stress exponent and the small grain sizes of
      our samples indicate that our two-phase material deformed by dislocation
      accommodated grain boundary sliding. In samples deformed to 1 < gamma < 7,
      elongated clusters of ferropericlase grains form thin layers in the olivine
      matrix, and small grains of ferropericlase appear at olivine grain boundaries and
      three- and four-grain junctions. By gamma ~ 14, a well-distributed mixture of
      small ferropericlase grains among the olivine grains developed. Microstructures
      exhibit similarities to both mechanical and chemical models proposed to describe
      the processes leading to phase mixing. Our results provide evidence for grain
      size reduction during phase mixing that results in a grain size significantly
      smaller than the value predicted by the single-phase recrystallization piezometer
      for olivine. Thus, phase mixing provides a mechanism for the persistent weakening
      of rocks that is important for developing and maintaining shear zones necessary
      for plate tectonics.This article is part of a discussion meeting issue 'Earth
      dynamics and the development of plate tectonics'.

PMID- 30275165
TI  - When crust comes of age: on the chemical evolution of Archaean, felsic
      continental crust by crustal drip tectonics.
AB  - The secular evolution of the Earth's crust is marked by a profound change in
      average crustal chemistry between 3.2 and 2.5 Ga. A key marker for this change is
      the transition from Archaean sodic granitoid intrusions of the tonalite
      trondhjemite-granodiorite (TTG) series to potassic (K) granitic suites, akin (but
      not identical) to I-type granites that today are associated with subduction
      zones. It remains poorly constrained as to how and why this change was initiated
      and if it holds clues about the geodynamic transition from a pre-plate tectonic
      mode, often referred to as stagnant lid, to mobile plate tectonics. Here, we
      combine a series of proposed mechanisms for Archaean crustal geodynamics in a
      single model to explain the observed change in granitoid chemistry. Numeric
      modelling indicates that upper mantle convection drives crustal flow and
      subsidence, leading to profound diversity in lithospheric thickness with thin
      versus thick proto-plates. When convecting asthenospheric mantle interacts with
      lower lithosphere, scattered crustal drips are created. Under increasing P-T
      conditions, partial melting of hydrated meta-basalt within these drips produces
      felsic melts that intrude the overlying crust to form TTG. Dome structures, in
      which these melts can be preserved, are a positive diapiric expression of these
      negative drips. Transitional TTG with elevated K mark a second evolutionary
      stage, and are blends of subsided and remelted older TTG forming K-rich melts and
      new TTG melts. Ascending TTG-derived melts from asymmetric drips interact with
      the asthenospheric mantle to form hot, high-Mg sanukitoid. These melts are small
      in volume, predominantly underplated, and their heat triggered melting of lower
      crustal successions to form higher-K granites. Importantly, this evolution
      operates as a disseminated process in space and time over hundreds of millions of
      years (greater than 200 Ma) in all cratons. This focused ageing of the crust
      implies that compiled geochemical data can only broadly reflect geodynamic
      changes on a global or even craton-wide scale. The observed change in crustal
      chemistry does mark the lead up to but not the initiation of modern-style
      subduction.This article is part of a discussion meeting issue 'Earth dynamics and
      the development of plate tectonics'.

PMID- 30275166
TI  - Magma oceans as a critical stage in the tectonic development of rocky planets.
AB  - Magma oceans are a common result of the high degree of heating that occurs during
      planet formation. It is thought that almost all of the large rocky bodies in the
      Solar System went through at least one magma ocean phase. In this paper, we
      review some of the ways in which magma ocean models for the Earth, Moon and Mars
      match present-day observations of mantle reservoirs, internal structure and
      primordial crusts, and then we present new calculations for the oxidation state
      of the mantle produced during the magma ocean phase. The crystallization of magma
      oceans probably leads to a massive mantle overturn that may set up a stably
      stratified mantle. This may lead to significant delays or total prevention of
      plate tectonics on some planets. We review recent models that may help alleviate
      the mantle stability issue and lead to earlier onset of plate tectonics.This
      article is part of a discussion meeting issue 'Earth dynamics and the development
      of plate tectonics'.

PMID- 30275167
TI  - Early earth geodynamics: cross examining the geological testimony.
AB  - Many studies link the presence of continents on Earth to the operation of plate
      tectonics. Radiogenic isotope data have, however, long consigned the bulk of
      crust generation and preservation to the murky realm of the Precambrian Earth,
      where the prevailing geodynamic systems are highly uncertain due to the sparse
      and complex nature of the geological record of these early eons. The purpose of
      this paper is to examine the nature of this geological record, considering the
      biases and artefacts that may undermine its fidelity, and to assess what are the
      most robust lines of evidence from which meaningful geodynamic inferences can be
      drawn. This is pursued with reference to Hadean detrital zircons, Archean gneiss
      complexes and Archean granite-greenstone terranes, and by considering isotopic
      proxies of crust-mantle interaction. The evidence reinforces long held views that
      the formation of some of the oldest continental nuclei involved a distinctive
      mode of planetary geodynamics that rests uneasily within definitions of modern
      style plate tectonics. A detailed interrogation of the oldest rocks, integrating
      multi-scale information from the best preserved whole-rock and mineral archives,
      and emphasizing careful selection at the sampling and analytical stages, will
      lead to the most robust input data for petrological and thermodynamic models of
      early Earth processes.This article is part of a discussion meeting issue 'Earth
      dynamics and the development of plate tectonics'.

PMID- 30275168
TI  - Earth dynamics and the development of plate tectonics.

PMID- 30275169
TI  - Association between tobacco prices and smoking onset: evidence from the TCP India
      Survey.
AB  - BACKGROUND: Tobacco use is prevalent among youth and adults in India. However,
      direct evidence on how increasing taxes or prices affect tobacco use onset is
      scarce. OBJECTIVE: To analyse the associations between cigarette and bidi prices
      and smoking onset in India, and how these associations differ by socioeconomic
      status. METHODOLOGY: The Wave 1 of the Tobacco Control Policy Evaluation India
      Survey by the International Tobacco Control Project contains information on the
      age at smoking onset for cigarettes and bidis. Using this information, data were
      expanded to a yearly pseudo-panel dataset that tracked respondents at risk of
      smoking onset from 1998 to 2011. The associations between bidi prices and bidi
      smoking onset, between cigarette prices and cigarette smoking onset, and between
      bidi and cigarette prices and any smoking onset were examined using a discrete
      time hazard model with a logit link function. Stratified analyses were conducted
      to examine the difference in these associations by rural versus urban division.
      RESULTS: We found that higher bidi prices were significantly associated with a
      lowered hazard of bidi smoking onset (OR 0.42, 95% CI 0.35 to 0.51). Higher
      cigarette prices were significantly (OR 0.87, 95% CI 0.83 to 0.92) associated
      with a lowered hazard of cigarette smoking onset among urban residents, but this
      association was non-significant when SEs were clustered at the state level. In
      addition, the association between increasing bidis prices and lowered hazards of
      bidi smoking onset was greater for urban residents than for rural ones (p<0.01).
      CONCLUSIONS: Under the new regime of a central goods and service system,
      policymakers may need to raise the prices of tobacco products sufficiently to
      curb smoking onset.

PMID- 30275170
TI  - Modelling the impact of a new tobacco product: review of Philip Morris
      International's Population Health Impact Model as applied to the IQOS heated
      tobacco product.
AB  - OBJECTIVES: We review the Population Health Impact Model (PHIM) developed by
      Philip Morris International and used in its application to the US Food and Drug
      Administration (FDA) to market its heated tobacco product (HTP), IQOS, as a
      modified-risk tobacco product (MRTP). We assess the model against FDA guidelines
      for MRTP applications and consider more general criteria for evaluating reduced
      risk tobacco products. METHODS: In assessing the PHIM against FDA guidelines, we
      consider two key components of the model: the assumptions implicit in the model
      (outcomes included, relative harm of the new product vs cigarettes, tobacco
      related diseases considered, whether dual or polyuse of the new product is
      modelled, and what other tobacco products are included) and data used to estimate
      and validate model parameters (transition rates between non-smoking, cigarette
      only smoking, dual use of cigarettes and MRTP, and MRTP-only use; and starting
      tobacco use prevalence). RESULTS: The PHIM is a dynamic state transition model
      which models the impact of cigarette and MRTP use on mortality from four tobacco
      attributable diseases. The PHIM excludes morbidity, underestimates mortality,
      excludes tobacco products other than cigarettes, does not include FDA-recommended
      impacts on non-users and underestimates the impact on other population groups.
      CONCLUSION: The PHIM underestimates the health impact of HTP products and cannot
      be used to justify an MRTP claim. An assessment of the impact of a potential MRTP
      on population health should include a comprehensive measure of health impacts,
      consideration of all groups impacted, and documented and justifiable assumptions
      regarding model parameters.

PMID- 30275171
TI  - The Role of Standing Variation in the Evolution of Weedines Traits in South Asian
      Weedy Rice (Oryza spp.).
AB  - Weedy rice (Oryza spp.) is a problematic weed of cultivated rice (O. sativa)
      around the world. Recent studies have established multiple independent
      evolutionary origins of weedy rice, raising questions about the traits and genes
      that are essential for the evolution of this weed. Among world regions, South
      Asia stands out due to the heterogeneity of its weedy rice populations, which can
      be traced to at least three origins: two through de-domestication from distinct
      cultivated rice varieties, and one from local wild rice (O. rufipogon/O. nivara).
      Here we examine five traits considered typical of or advantageous to weedy rice
      in weedy, cultivated and wild rice samples from South Asia. We establish that
      convergence among all three weed groups occurs for easy seed shattering, red
      pericarp color, and compact plant architecture, suggesting that these traits are
      essential for weed success in the South Asian agricultural environment. A high
      degree of convergence for black hull color is also seen among weeds with wild
      ancestors and weeds evolved from the aus cultivated rice group. We also examine
      polymorphism in five known domestication candidate genes, and find that Rc and
      Bh4 are associated with weed seed pericarp color and hull color, respectively,
      and weedy alleles segregate in the ancestral populations, as do alleles for the
      seed dormancy-linked gene Sdr4 The presence of a domestication related allele at
      the seed shattering locus, sh4, in weedy rice populations with cultivated
      ancestry supports a de-domestication origin for these weedy groups, and raises
      questions about the reacquisition of the shattering trait in these weedy
      populations. Our characterization of weedy rice phenotypes in South Asia and
      their associated candidate genes contribute to the emerging understanding of the
      mechanisms by which weedy rice evolves worldwide, suggesting that standing
      ancestral variation is often the source of weedy traits in independently evolved
      groups, and highlighting the reservoir of genetic variation that is present in
      cultivated varieties as well as in wild rice, and its potential for phenotypic
      evolution.

PMID- 30275173
TI  - Efficacy of a Covalent ERK1/2 Inhibitor, CC-90003, in KRAS Mutant Cancer Models
      Reveals Novel Mechanisms of Response and Resistance.
AB  - : As a critical signaling node, extracellular signal-regulated kinases (ERK1/2)
      are attractive drug targets, particularly in tumors driven by activation of the
      Mitogen Activated Protein Kinase (MAPK) pathway. Utility of targeting the MAPK
      pathway has been demonstrated by clinical responses to inhibitors of MEK1/2 or
      RAF kinases in some mutant-BRAF activated malignancies. Unlike tumors with
      mutations in BRAF, those with mutations in KRAS (>30% of all cancers and >90% of
      certain cancer types) are generally not responsive to inhibitors of MEK1/2 or
      RAF. Here, a covalent ERK1/2 inhibitor, CC-90003 was characterized and shown to
      be active in preclinical models of KRAS mutant tumors. A unique occupancy assay
      was used to understand the mechanism of resistance in a KRAS mutant patient
      derived xenograft model (PDX) of colorectal cancer (CRC). Finally, combination of
      CC-90003 with Docetaxel achieved full tumor regression and prevented tumor
      regrowth after cessation of treatment in a PDX model of lung cancer. This effect
      corresponded to changes in a stemness gene network, revealing a potential effect
      on tumor stem cell reprograming. IMPLICATIONS: Here, a covalent ERK1/2 inhibitor
      (CC-90003) is demonstrated to have preclinical efficacy in models of KRAS mutant
      tumors, which present a therapeutic challenge for currently available therapies.

PMID- 30275175
TI  - Surgical Endoscopic Vacuum-assisted Closure Therapy (EVAC) in Treating
      Anastomotic Leakages After Major Resective Surgery of Esophageal and Gastric
      Cancer.
AB  - BACKGROUND/AIM: Endoscopic vacuum-assisted closure therapy (EVAC) is a promising
      new technique for repairing upper gastrointestinal defects of different
      etiologies. As of 2018, however, no standardized recommendation exists. This
      article reviewed EVAC in treating anastomotic leakage following major resective
      surgery of esophageal (EC) and gastric cancer (GC). MATERIALS AND METHODS: Only
      English-language literature was investigated. Only studies or data on EC and GC
      were included. Seven popular search engines (PubMed, Web of Science,
      ScienceDirect, Scopus, Google Scholar, ResearchGate, PubFacts) were utilized.
      RESULTS: A total of 29 studies (17 retrospective, six prospective and six case
      reports) with a total of 209 patients. Range of anastomotic leakage closure was
      66.7-100%. Anastomotic stricture was the most frequent long-term related
      complication (18 cases). CONCLUSION: EVAC appears to be an extremely useful
      treatment for postsurgical anastomotic leakage in patients with EC/GC. Almost all
      kinds of anastomotic leakage (silent to symptomatic, small to large) seem to be
      amenable to this technique.

PMID- 30275172
TI  - Characterization of Genetic and Epigenetic Variation in Sperm and Red Blood Cells
      from Adult Hatchery and Natural-Origin Steelhead, Oncorhynchus mykiss.
AB  - While the goal of most conservation hatchery programs is to produce fish that are
      genetically and phenotypically indistinguishable from the wild stocks they aim to
      restore, there is considerable evidence that salmon and steelhead reared in
      hatcheries differ from wild fish in phenotypic traits related to fitness. Some
      evidence suggests that these phenotypic differences have a genetic basis (e.g.,
      domestication selection) but another likely mechanism that remains largely
      unexplored is that differences between hatchery and wild populations arise as a
      result of environmentally-induced heritable epigenetic change. As a first step
      toward understanding the potential contribution of these two possible mechanisms,
      we describe genetic and epigenetic variation in hatchery and natural-origin adult
      steelhead, Oncorhynchus mykiss, from the Methow River, WA. Our main objectives
      were to determine if hatchery and natural-origin fish could be distinguished
      genetically and whether differences in epigenetic programming (DNA methylation)
      in somatic and germ cells could be detected between the two groups. Genetic
      analysis of 72 fish using 936 SNPs generated by Restriction Site Associated DNA
      Sequencing (RAD-Seq) did not reveal differentiation between hatchery and natural
      origin fish at a population level. We performed Reduced Representation Bisulfite
      Sequencing (RRBS) on a subset of 10 hatchery and 10 natural-origin fish and
      report the first genome-wide characterization of somatic (red blood cells (RBCs))
      and germ line (sperm) derived DNA methylomes in a salmonid, from which we
      identified considerable tissue-specific methylation. We identified 85
      differentially methylated regions (DMRs) in RBCs and 108 DMRs in sperm of
      steelhead reared for their first year in a hatchery environment compared to those
      reared in the wild. This work provides support that epigenetic mechanisms may
      serve as a link between hatchery rearing and adult phenotype in steelhead;
      furthermore, DMRs identified in germ cells (sperm) highlight the potential for
      these changes to be passed on to future generations.

PMID- 30275174
TI  - Immune Therapeutics in the Treatment of Advanced Gastric and Esophageal Cancer.
AB  - Systemic chemotherapy is the mainstay of therapy in patients with advanced
      gastric and esophageal cancer, but has multiple drawbacks including lack of
      durable efficacy and dose limited toxicities. Recent clinical trials data on the
      efficacy of immune therapy in this patient group have shed light on its potential
      as an alternative treatment option. Checkpoint inhibitors, specifically the anti
      PD-1/PD-L1 inhibitors, seem to be beneficial for a subgroup of patients with
      advanced gastric or esophageal cancer who have progressed on multiple systemic
      chemotherapies. As clinical trials results mature, it will become apparent
      whether checkpoint inhibitors are effective in other treatment settings such as
      in first-line therapy or adjuvant therapy. Although the toxicity of checkpoint
      inhibitors is generally unpredictable, they tend to be more manageable and better
      tolerated than the toxicities of systemic chemotherapy. Furthermore, recent
      research in molecular subtyping of esophageal and gastric cancer are paving way
      for better treatment response prediction and patient selection for checkpoint
      inhibitor therapies. Compared to checkpoint inhibitors, other types of immune
      therapies such as cancer vaccines, and adoptive cell therapies have yet to be
      proven effective in esophageal and gastric cancer and are further away from
      clinical use. Immune therapy seems poised to take a firm position as part of the
      therapeutic armamentarium for advanced gastric and esophageal cancer and future
      clinical trials will show the extent of its application in different treatment
      settings in this patient population.

PMID- 30275176
TI  - Spinal Ewing Sarcoma Debuting with Cord Compression: Have We Discovered the
      Thread of Ariadne?
AB  - Ewing's sarcoma (ES) of the spine with cord or radicular compression as an
      initial sign is infrequent. It is unclear, in alleviating a neurological deficit,
      whether decompressive laminectomy is preferred over chemotherapy. Herein, a
      literature review of the treatment approaches to the primary or metastatic ES of
      the spine has been performed. Collected data included clinical features of the
      patients, treatment, and outcome. There are reported 69 cases with initial
      presentation of cord or radicular compression of spinal cord, arising from
      primary or metastatic ES, treated either with initial chemotherapy and/or
      radiotherapy (RT) (33.33%, n=23), or decompressive surgery (66.66%, n=46). The
      median age at diagnosis was 17.95 years old (range=0.06-60), and 38 patients
      (55.07%) were male. Eighteen (78.26%) were initially treated with chemotherapy
      combined with RT, whereas 3 (13.04%) were managed with RT alone. One patient
      (4.35%) received only corticosteroids, while there are not available data for the
      treatment of another one (4.35%). The remaining 46 patients (66.66%) were
      initially treated with decompressive surgery. Among them, 40 (57.97%) received
      postoperative chemotherapy, RT or combined modality therapy, whereas 6 patients
      (8.69%) were not treated adjuvantly. Sixteen out of 23 patients (69.6%) treated
      with systemic therapy, and 37 from 46 (80.43%) of those managed with
      decompressive laminectomy were still alive at a mean follow-up period of 2.11
      years (range=0.16-6) and 3.45 years (range=0.16-26.08), respectively. To
      summarize, spinal resection and reconstruction followed by adjuvant treatment
      reduce the risk of local recurrence, and improve long-term survival. However, ES
      of the spine is not a distinct clinical entity and can be either managed with
      chemotherapy and/or RT, similarly to other localization.

PMID- 30275177
TI  - Effect of Perioperative Lidocaine and Cisplatin on Metastasis in a Murine Model
      of Breast Cancer Surgery.
AB  - BACKGROUND/AIM: Mortality from breast cancer is usually attributable to
      metastasis. In vitro data suggest that amide local anaesthetics, e.g. lidocaine,
      inhibit metastasis by multiple mechanisms and recent in vivo data support this.
      Experimental data also suggest that opioids may inhibit cisplatin chemotherapy.
      Whether lidocaine would influence cisplatin chemotherapy has not been evaluated.
      MATERIALS AND METHODS: 4T1 cells were injected into the mammary gland of
      immunocompetent female BALB/c mice, with resection of the tumour under
      sevoflurane anaesthesia one week later. Mice (n=45) were randomized into one of
      three groups: The cisplatin group received 3 mg.kg-1 cisplatin; cisplatin and
      lidocaine group received 3 mg.kg-1 cisplatin and lidocaine bolus of 1.5 mg.kg-1
      followed by an infusion of 2 mg.kg-1.h-1 The control group received sevoflurane
      only. All agents were given perioperatively. After 14 postoperative days, post
      mortem lung, serum and liver samples were collected. Primary outcome measure was
      lung metastasis colony count. RESULTS: During sevoflurane anaesthesia, the
      addition of lidocaine to cisplatin significantly decreased metastatic lung colony
      count [(mean+/-SD) (157+/-87)] compared to control [846+/-581, (p=0.001)], and
      cisplatin alone [580+/-383, (p=0.018)]. However, liver metastasis colony count
      was not reduced with the combination of cisplatin and lidocaine (9.3+/-13.9) when
      compared to control (74.7+/-257.3), p=0.78 or to cisplatin alone (110+/-388.8),
      p=0.569. Serum VEGF and interleukin-6 concentrations were not significantly
      different. CONCLUSION: In a 4T1 murine model of breast cancer surgery, under
      sevoflurane anaesthesia, lidocaine enhanced the metastasis-inhibiting action of
      cisplatin. Clinical evaluation of the hypothesis that co-administration of
      systemic lidocaine during cisplatin chemotherapy seems warranted.

PMID- 30275178
TI  - Thiasyrbactins Induce Cell Death via Proteasome Inhibition in Multiple Myeloma
      Cells.
AB  - BACKGROUND/AIM: Proteasome inhibition is a validated therapeutic strategy for the
      treatment of refractory and relapsed multiple myeloma (MM) and mantle cell
      lymphoma. We previously showed that thiasyrbactins (NAM compounds) are inhibitors
      with an affinity for the trypsin-like (T-L, beta2) site of the constitutive
      proteasome, and more profoundly for the T-L site of the immunoproteasome.
      MATERIALS AND METHODS: In this study, the biological activity of three NAM
      compounds was evaluated using four MM cell lines (ARD, U266, MM1R, and MM1S). We
      assessed the effect of (NAM-93, NAM-95, and NAM-105 on cell viability, as well as
      cell-based proteasomal activities, and determined the EC50 and Ki50 values,
      respectively. RESULTS: MM cells were most sensitive to NAM-93 with EC50 values
      <0.75 MUM after 48 h of treatment. NAM-105 had a similar profile in most of the
      MM cells with EC50 values ranging between 0.42 and 3.02 MUM. The level of
      inhibition of the proteasome T-L sub-catalytic activity in actively-growing MM
      cells was similar for NAM-93 and NAM-105. However, in each cell line, NAM-93 was
      more effective than NAM-105 at inhibiting overall trypsin-like sub-catalytic
      activity while NAM-105 was typically more effective at inhibiting overall
      chymotrypsin-like (CT-L, beta5) sub-catalytic activity. CONCLUSION: These results
      show for the first time the proteasome-targeted biological activity of
      thiasyrbactins in MM tumor cells.

PMID- 30275179
TI  - Panobinostat and Nelfinavir Inhibit Renal Cancer Growth by Inducing Endoplasmic
      Reticulum Stress.
AB  - BACKGROUND/AIM: There is no curative treatment for patients with advanced renal
      cancer. We believed that the combination of the histone deacetylase inhibitor
      panobinostat and the human immunodeficiency virus protease inhibitor nelfinavir
      would kill renal cancer cells by inducing endoplasmic reticulum (ER) stress.
      MATERIALS AND METHODS: Using renal cancer cells (769-P, 786-O, Caki-2), the
      ability of this combination to induce ER stress and its mechanism of action were
      investigated. RESULTS: The combination of drugs induced apoptosis and inhibited
      cancer growth effectively both in vitro and in vivo. Mechanistically, the
      combination induced ER stress and histone acetylation cooperatively. ER stress
      induction was shown to play a pivotal role in the anticancer effect of the
      combination because the protein synthesis inhibitor cycloheximide significantly
      attenuated combination-induced apoptosis. Nelfinavir was also found to increase
      the expression of the mammalian target of rapamycin (mTOR) inhibitor AMP
      activated protein kinase (AMPK) and inhibited the panobinostat-activated mTOR
      pathway. CONCLUSION: Panobinostat and nelfinavir inhibit renal cancer growth by
      inducing ER stress.

PMID- 30275180
TI  - Hotspot Mutations Detectable by Next-generation Sequencing in Exhaled Breath
      Condensates from Patients with Lung Cancer.
AB  - BACKGROUND: Genetic alterations occurring in lung cancer are the basis for
      defining molecular subtypes and essential for targeted therapies. Exhaled breath
      condensate (EBC) is a form of non-invasive sample that, amongst components,
      contains DNA from pulmonary tissue. Next-generation sequencing (NGS) was herein
      used to analyze mutations in EBC from patients with lung cancer. MATERIALS AND
      METHODS: EBC was collected from 26 patients with cancer and 20 healthy controls.
      Amplicon-based sequencing using Ion Ampliseq Colon and Lung Cancer gene panel v2
      was applied. RESULTS: The sequencing was successful in 17 patients and 20
      controls. EBC from patients revealed 39 hotspot mutations occurring in:
      adenomatous polyposis coli (APC), v-raf murine sarcoma viral oncogene homolog B
      (BRAF), discoidin domain receptor tyrosine kinase 2 (DDR2), epidermal growth
      factor receptor (EGFR), erb-b2 receptor tyrosine kinase 4 (ERBB4), F-box and WD
      repeat domain containing 7 (FBXW7), fibroblast growth factor receptor 1 (FGFR1),
      FGFR3 (fibroblast growth factor receptor 3), Kirsten rat sarcoma viral oncogene
      homolog (KRAS), mitogen-activated protein kinase kinase 1 (MAP2K1), met proto
      oncogene (MET), neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS),
      phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA),
      phosphatase and tensin homolog (PTEN), ret proto-oncogene (RET), SMAD family
      member 4 (SMAD4), serine/threonine kinase 11 (STK11), and tumor protein p53
      (TP53) genes. EBC from controls revealed 35 hotspot mutations. The average mutant
      allele fraction was higher in patients than controls. CONCLUSION: NGS can
      identify mutations in EBCs from patients with lung cancer. This could provide a
      promising non-invasive method for the assessment of gene mutations in lung
      cancer.

PMID- 30275181
TI  - Color-coded Imaging of the Circulating Tumor Cell Microenvironment.
AB  - BACKGROUND/AIM: Circulating tumor cells (CTCs) may initiate metastasis. Some
      studies show that the number of CTCs and existence of CTC clusters can be
      prognostic. In the present study, our color-coded imaging nude mouse model of
      metastatic lymphoma was utilized to investigate the microenvironment of CTC
      clusters using fluorescent-protein imaging. MATERIALS AND METHODS: EL-4 mouse
      lymphoma cells expressing red fluorescent protein (RFP) were injected into the
      spleen of transgenic C57B/6-green fluorescent protein (GFP) mice. Three weeks
      later, the number of CTCs and CTC clusters both in heart blood and portal blood
      were quantified and characterized using confocal microscopy for color-coded
      imaging. RESULTS: There was no significant difference in the number of CTCs
      between heart and portal blood. CTC clusters comprised 8.8% of CTCs, determined
      by color-coded imaging. Heterotypic CTC clusters containing other types of cells
      were distinguishable from homotypic CTCs. Heterotypic CTC clusters comprising
      cancer cells and fibroblasts were more rare than homotypic ones. Heterotypic CTC
      clusters with fibroblasts were observed only in portal blood, not in heart blood.
      CONCLUSION: CTCs can have variable properties depending on the blood source. CTCs
      can form clusters, which may contain fibroblast that may play a role in promoting
      CTC metastasis. Our results demonstrate the concept of the CTC microenvironment
      (CME), which may play a critical role in CTC behavior, including of metastasis.

PMID- 30275183
TI  - Theranostics with Hybrid Liposomes in an Orthotopic Graft Model Mice of Breast
      Cancer.
AB  - BACKGROUND/AIM: This study aimed to elucidate the therapeutic effects of hybrid
      liposomes (HL) composed of L-alpha-dimyristylphosphatidylcholine (DMPC) and
      polyoxyethylene [25] dodecyl ether (C12(EO)25) and the ability of HL-containing
      fluorescent probe to detect cancer in orthotopic graft model mice of breast
      cancer (MDA-MB-453). MATERIALS AND METHODS: HL composed of 90 mol% DMPC and 10
      mol% C12(EO)25 were prepared by the sonication method. Anti-tumor activities of
      HL were investigated in vivo using orthotopic graft-bearing mice of MDA-MB-453
      cells. RESULTS: With regard to the therapeutic effects of HL for breast cancer,
      HL inhibited the growth of MDA-MB-453 cells and induced apoptosis. Intravenous
      administration of HL resulted in a remarkable reduction of relative tumor weight
      in orthotopic graft model mice of breast cancer. The TUNEL assay revealed that
      this effect was due to induction of apoptosis. With regard to detection
      (diagnosis) of breast cancer, enhanced accumulation of HL carrying a fluorescence
      probe (Indocyanine green; ICG) was observed for MDA-MB-453 cells, although no
      accumulation of HL/ICG was obtained for normal breast cells. Enhanced
      accumulation of HL/ICG into the tumor of orthotopic graft model mice of breast
      cancer was observed. CONCLUSION: HL and HL/ICG could be theranostic targets since
      they showed therapeutic effects and ability to detect (diagnose) cancer in an
      orthotopic graft model mouse of breast cancer (MDA-MB-453).

PMID- 30275182
TI  - Oral Recombinant Methioninase Combined with Caffeine and Doxorubicin Induced
      Regression of a Doxorubicin-resistant Synovial Sarcoma in a PDOX Mouse Model.
AB  - BACKGROUND/AIM: Synovial sarcoma (SS) is a recalcitrant neoplasm with low
      chemosensitivity. We recently reported that recombinant methioninase (rMETase)
      inhibited SS growth in a patient-derived orthotopic xenograft (PDOX) mouse model
      and was more effective when administered in combination with the first-line drug
      doxorubicin (DOX). Caffeine enhances the efficacy of anticancer drugs by
      overcoming drug-induced cell-cycle arrest and increasing subsequent apoptosis.
      Here, we determined the efficacy of oral recombinant methioninase (o-rMETase) in
      combined with caffeine on an SS-PDOX model. MATERIALS AND METHODS: Mice bearing
      SS-PDOX tumors were randomized into four treatment groups of six: Untreated
      control; o-rMETase alone; o-rMETase with caffeine; DOX plus o-rMETase with
      caffeine. Tumor size and body weight were measured during the treatment and
      plasma L-methionine (MET) levels were measured at the end of treatment. RESULTS:
      All treatments significantly inhibited SS-PDOX tumor growth. Combining caffeine
      with o-rMETase was more effective than o-rMETase alone. DOX combined with o
      rMETase and caffeine led to regression of SS-PDOX. Plasma MET levels were reduced
      with o-rMETase treatment. CONCLUSION: These results suggest that combining o
      rMETase and caffeine along with first-line chemotherapy can be highly effective
      for SS and has clinical potential for this recalcitrant disease.

PMID- 30275184
TI  - Cold Physical Plasma Selectively Elicits Apoptosis in Murine Pancreatic Cancer
      Cells In Vitro and In Ovo.
AB  - BACKGROUND/AIM: Poor prognosis of pancreatic cancer has remained almost unchanged
      in recent years. Cold physical plasma was suggested as an innovative anticancer
      strategy, but its selective killing activity of malignant over non-malignant
      cells has only partially been explored. The present study aimed at exploring the
      effect of cold physical plasma on cellular viability. MATERIALS AND METHODS:
      Induction of cell death and apoptosis by cold physical plasma was investigated in
      murine PDA6606 pancreatic cancer cells and primary murine fibroblasts in vitro
      (2D and 3D cultures) and in ovo. RESULTS: Plasma increased apoptosis in PDA6606
      to a significantly higher extent compared to fibroblasts. Antioxidants abrogated
      these effects, suggesting a prime role of reactive oxygen species in plasma
      induced apoptosis. Plasma increased apoptosis of 3D PDA6606 multicellular spheres
      grown in vitro and in ovo, to significantly higher rates compared to that of
      fibroblasts, with minimum in ovo inflammation or necrosis observed by hematoxylin
      and eosin staining (H&E). CONCLUSION: These data support the future intra
      operative application of cold physical plasma for the treatment of microscopic
      residual tumor tissue after surgical resection.

PMID- 30275185
TI  - Absence of HER2 Expression of Circulating Tumor Cells in Patients with Non
      Metastatic Esophageal Cancer.
AB  - BACKGROUND/AIM: The clinical significance of circulating tumor cells (CTC) in non
      metastatic esophageal cancer (EC) remains controversial and the cellular and
      molecular characteristics of CTCs are poorly understood. Especially the frequency
      and oncological impact of HER2 expression in CTCs in patients with EC have not
      been evaluated until now. MATERIALS AND METHODS: In this single-center,
      prospective study, peripheral blood samples were obtained preoperatively from 45
      patients who were diagnosed with resectable EC. CTC detection and HER2 expression
      were performed using the CellSearch System. Data were correlated with
      clinicopathological parameters and patient outcomes. RESULTS: The study included
      13 patients with squamous cell carcinomas (SCC) and 32 patients with
      adenocarcinomas (AC). HER2 gene amplification in the primary tumor was detected
      in 9.1% of patients. One or more CTCs were detected in 15.6% (SCC 1/13; AC 6/32)
      of the patients. None of the detected CTCs showed HER2 expression. Patients with
      CTCs showed significantly shorter relapse-free (p<0.001) and overall survival
      (p=0.015) than CTC-negative patients. CONCLUSION: This is the first study
      analyzing HER2 expression and the clinical significance of CTCs in patients with
      non-metastatic EC using an automated immunomagnetic detection system. HER2
      expression in CTCs is very rare in patients with non-metastatic EC and seems to
      have a low clinical and oncological impact.

PMID- 30275187
TI  - Relationship Between the Structure of Methoxylated and Hydroxylated Flavones and
      Their Antiproliferative Activity in HL60 Cells.
AB  - As part of our continuing investigation on flavonoid derivatives as potential
      anticancer substances, a series of methoxylated and hydroxylated flavones was
      synthesized, and their cytotoxic and anti-proliferative activity was evaluated in
      leukemic HL60 cells. Their structure-activity relationship was also investigated.
      The correlation between the methoxylation/hydroxylation pattern and
      antiproliferative activity revealed the importance of the 5,4'- and 3',4'
      dihydroxyl moieties in flavone nucleus.

PMID- 30275186
TI  - The Contribution of MMP-7 Promoter Polymorphisms to Taiwan Lung Cancer
      Susceptibility.
AB  - BACKGROUND/AIM: Matrix metalloproteinase-7 (MMP-7) plays an important role in
      metastasis behavior of cancer cells, and overexpression of MMP-7 has been
      associated with poor prognosis in non-small cell lung cancer. However, the
      contribution of various genotypes of MMP-7 has not yet been investigated in lung
      cancer in Taiwan. Therefore, this study aimed to investigate the association of
      MMP-7 genotypes with lung cancer risk among the Taiwanese. MATERIALS AND METHODS:
      In this hospital-based case-control study, genotypes and distributions at two
      promoter sites of MMP-7, A-181G and C-153T, were determined, and their
      association with lung cancer risk in Taiwan was evaluated among 358 lung cancer
      patients and 716 age- and gender-matched healthy control individuals. In
      addition, the interaction of MMP-7 genotypes and smoking status were also
      examined. RESULTS: The percentages of variant AG and GG at MMP-7 A-181G in the
      lung cancer group were similar to the control group (12.8% and 2.3% vs. 11.3% and
      1.5%, respectively; ptrend=0.5294). The allelic frequency distribution analysis
      showed that the variant G allele at MMP-7 A-181G conferred non-significant
      elevated lung cancer risk compared to the wild-type A allele [odds ratio
      (OR)=1.18, 95% confidence interval (CI)=0.85-1.66, p=0.2289]. As for the
      genotypes of MMP-7 C-153T, all the studied Taiwanese population was of CC
      genotype. Furthermore, there was no obvious joint effect of MMP-7 A-181G genotype
      and smoking status on the lung cancer risk. No statistically significant
      correlation was observed between MMP-7 A-181G genotype distributions and gender.
      CONCLUSION: There was no evidence that the genotypes of MMP-7 A-181G may act as a
      biomarker in determining personal susceptibility to lung cancer in Taiwan.

PMID- 30275188
TI  - P-gp Inhibition by the Anti-psychotic Drug Pimozide Increases Apoptosis, as well
      as Expression of pRb and pH2AX in Highly Drug-resistant KBV20C Cells.
AB  - BACKGROUND/AIM: The present study was designed to identify drugs that could
      sensitize P-glycoprotein (P-gp)-overexpressing resistant KBV20C cancer cells to
      treatment with Halaven (HAL) or vincristine (VIC). MATERIALS AND METHODS: Using
      relatively low doses or IC50 concentrations of drugs to sensitize anti-mitotic
      drug-resistant KBV20C cells, pimozide (PIM) sensitized HAL-resistant KBV20C
      cancer cells, with higher P-gp inhibitory activity than another anti-psychotic
      drug, fluphenazine (FLU). RESULTS: The first-generation P-gp inhibitor verapamil
      required a dose that was similar to that of PIM for P-gp inhibition, suggesting
      that PIM has a similar specificity for binding P-gp to prevent efflux of anti
      mitotic drugs. Furthermore, co-treatment with PIM and another anti-mitotic drug,
      VIC, also increased sensitization of KBV20C cells, suggesting that PIM can be
      combined with other anti-mitotic drugs to sensitize resistant cancer cells. PIM
      caused a reduction in cell viability and an increase in the number of cells
      arresting at the G2 phase of the cell cycle. PIM induced both early and late
      apoptosis in KBV20C cells in response to HAL treatment. Furthermore, the DNA
      damage marker pH2AX, the cell-cycle protein pRb, and the pro-apoptotic protein C
      PARP levels increased after HAL-PIM co-treatment, indicative of a mechanism
      involving G2 phase arrest and an increase in the number of cells undergoing
      apoptosis. CONCLUSION: PIM may be a promising therapeutic agent for the treatment
      of cancers that are resistant to anti-mitotic drugs.

PMID- 30275189
TI  - miR-3148 Is a Novel Onco-microRNA that Potentiates Tumor Growth In Vivo.
AB  - BACKGROUND/AIM: Alterations of microRNA expression in three-dimensional spheroids
      were examined to identify novel microRNAs that might be associated with
      tumorigenesis. MATERIALS AND METHODS: Using microRNA microarray analysis, we
      screened for microRNAs that were dramatically up-regulated inside three
      dimensional spheroids in genetically-modified HCT116 human colon cancer cells
      expressing Copepoda Green Fluorescent Protein under hypoxia. RESULTS: miR-3148
      was identified as a possible candidate onco-microRNA. A growth advantage of
      HCT116 cells stably expressing miR-3148 (HCT116-miR3148) was observed compared to
      parental cells in vivo, but not in vitro. Additionally, no change in growth under
      hypoxic or starvation conditions was seen in these cells cultured two
      dimensionally; however, HCT116-miR3148 cells maintained as three-dimensional
      spheroids were highly resistant to hypoxic conditions. HCT116-miR3148 cells were
      more sensitive to mitogen-activated protein kinase (MAPK) kinase inhibitors and
      extracellular signal-regulated kinase (ERK) inhibitors. CONCLUSION: MiR-3148 may
      be a novel onco-microRNA that protects cancer cells from serious stress
      conditions through the MAPK/ERK pathway, especially in vivo.

PMID- 30275190
TI  - IL-8-251T>A (rs4073) Polymorphism Is Associated with Prognosis in Gastric Cancer
      Patients.
AB  - BACKGROUND/AIM: Inflammation is a key process in gastric carcinogenesis.
      Cytokines are mediators of inflammation and are involved in metastasis and
      tumorigenicity. We previously assessed the role of cytokine gene polymorphisms in
      gastric cancer risk in Chile. In the present study, we aimed to analyze whether
      these polymorphisms are associated with overall survival (OS) in gastric cancer
      (GC) patients. PATIENTS AND METHODS: A total of 153 individuals with GC diagnosis
      were followed-up for at least 2 years. Hazard ratios (HR) were estimated from Cox
      regression models using SNPs as predictor variables. The following SNPs were
      genotyped for study using a TaqMan assay: rs16944 (IL1B -511C>T); rs4073 (IL8 
      251 T>A); rs2275913 (IL-17 -197G>A); rs1800872 (IL10 -592 C>A); rs1800896 (IL10 
      1082A>G); rs28372698 (IL32). RESULTS: Interleukin-8 rs4073 (IL-8 -251T>A) showed
      association with OS under the dominant model (TA + AA) only when adjusted by
      clinicopathological variables (HR=1.64, 95%CI=1.05-2.55, p=0.030, q-value=0.18),
      but not with the univariate model (HR=1.51, 95%CI=0.98-2.31, p=0.062, q
      value=0.37). No significant differences were observed after adjusting for
      population stratification (PC1 and PC2 from Principal Component Analysis using
      genotypes from Infinium Global Screening Array). After stratification by
      clinicopathological variables, the association with shorter overall survival was
      higher among patients with diffuse-type tumors (HR=2.24, 95%CI=1.16-4.45) and
      patients with tumor size >5 cm (HR=1.79, 95%CI=1.08-2.97). CONCLUSION: These
      results suggest a role of IL-8 rs4073 in cancer prognosis. Its use as a
      prognostic marker of GC survival warrants further investigation.

PMID- 30275191
TI  - Evaluation of Therapeutic Potential of Phenoxodiol, a Novel Isoflavone Analog, in
      Renal Cancer Cells.
AB  - BACKGROUND/AIM: In the present study, the antineoplastic activity and mechanism
      of action of phenoxodiol, a novel isoflavone analog, was investigated in renal
      cancer cells. MATERIALS AND METHODS: A panel of renal cancer cells (769-P, 786-O,
      Caki-2) was treated with phenoxodiol in vitro, and the efficacy of treatment was
      evaluated. RESULTS: MTS assay results showed that phenoxodiol decreased renal
      cancer viability in a dose-dependent manner. In addition, it inhibited colony
      formation significantly and perturbed the cell cycle. Treatment with phenoxodiol
      increased the number of annexin-V-positive cells as well as the expression of
      cleaved poly ADP ribose polymerase, demonstrating that phenoxodiol induced
      apoptosis in renal cancer cells. Phenoxodiol also inhibited Akt pathway via
      dephosphorylation of Akt. CONCLUSION: Phenoxodiol inhibited Akt pathway and
      induced apoptosis of renal cancer cells. The present study provides a theoretical
      basis for future development of a novel therapy effective against renal cancer.

PMID- 30275192
TI  - Differential Effects of In Vitro Treatment with Cinobufotalin on Three Types of
      Ovarian Cancer Cells.
AB  - BACKGROUND/AIM: Cinobufotalin (CINO), a cardiotonic steroid, has been used as an
      anticancer agent. This study assessed the cell-specific effect of CINO on SK-OV
      3, CRL-1978 and CRL-11731 ovarian cancer cells which differ in terms of their
      respective karyotypes. MATERIALS AND METHODS: Cell cultures were treated with
      CINO (0.1, 1, 5 and 10 MUM) for 24, 48, and 72 h. Cell proliferation, migration,
      and invasion were measured using CellTiter, Cytoselect, and FluoroBlock assays,
      respectively. Expression of proliferating cell nuclear antigen (PCNA) was
      evaluated by western blot analysis. Cell viability was determined by fluorescence
      activated cell sorting. Immunofluorescence was performed using Annexin-V staining
      and fluorescein isothiocyanate (FITC). Mitochondrial membrane potential (MMP) was
      measured using MitoTrackerTM Red. RESULTS: CINO at 0.5 MUM inhibited SK-OV-3, CRL
      1978, and CRL-11731 proliferation, migration, and invasion. Each cell type
      differed in response to CINO doses for PCNA, Annexin-V expression and MMP.
      CONCLUSION: The antineoplastic property of CINO is consistent, but its mode of
      action varies among cell lines.

PMID- 30275193
TI  - Identification of Two Types of Stem Cells in Methylene Blue-stained Sections of
      Untreated and Diethylstilbestrol-treated Human Prostate Cancer and Their
      Characterization by Immunogold Localization of CD133.
AB  - BACKGROUND: The basal compartment of the prostatic acinus harbors stem and basal
      cells, whereas the luminal compartment contains cuboidal and columnar cells.
      Mutation in the genes of stem cells is required for benign (normal) prostate to
      develop into prostatic adenocarcinoma. Stem/basal cells survive androgen
      deprivation therapy in humans and castrated mice to repopulate glandular cells by
      proliferation when stimulated by androgen. We hypothesized that using different
      embedding and staining methods, it would be possible to identify two types of
      stem cells in human prostate by localization of CD133. MATERIALS AND METHODS:
      Prostate biopsy or prostatectomy pieces from 13 untreated and eight
      diethylstilbestrol-treated men with prostate cancer were sectioned, stained by
      methylene blue and CD133 was localized by immunogold technique. RESULTS:
      Methylene blue stained basic proteins in dark basal cells, but not in light
      cells. Light basal cells expressed androgen receptors and dark cells estrogen
      receptors. Light and dark cells expressed CD133, indicating them to be stem
      cells. Light stem cells produced the lineage of columnar/cuboidal cells. Estrogen
      dependent dark cells produced a lineage of columnar/cuboidal cells, that also
      expressed estrogen receptors. CONCLUSION: Our analysis indicates that stem/basal
      cells are privileged cells in the basal compartment. Stem cells are not under the
      regulation of steroid hormones, whereas their lineage of cuboidal/columnar cells
      are. The lineage of androgen-dependent cells are columnar/cuboidal cells and the
      lineage of estrogen-dependent cells are also columnar/cuboidal cells. Epon
      embedding and methylene blue staining showed two types of CD133-positive stem
      cells in prostate. Paraffin sections did not show two types of stem cells in
      prostate and bone marrow leukemia cells. Our study indicates the continuity of
      embryonic stem cells into adult prostate as organ-specific stem cells. To our
      knowledge, this is the first study to identify two types of stem cells in human
      prostate.

PMID- 30275194
TI  - Differential Mobility of Breast Cancer Cells and Normal Breast Epithelial Cells
      Under DC Electrophoresis and Electroosmosis.
AB  - BACKGROUND/AIM: Breast cancer has shown improved prognosis over the years, yet
      due to different types of breast cancer and different phenotypes of breast cancer
      cells, it is essential to have an accurate diagnostic procedure. MATERIALS AND
      METHODS: A unique methodology employing direct current (DC) electrophoresis and
      electroosmosis in fabricated microfluidic devices was used. This phenomenon was
      used to discern breast cancer cells from normal breast epithelial cells based on
      their electrophoretic mobility and electroosmosis. RESULTS: Breast cancer cells
      (MDA-MB-231) rapidly covered the wound in scratch assay compared to mammary
      epithelial cells (MCF-10A). However, under DC electrophoresis and electroosmosis
      MCF-10A cells were observed to move at higher velocities compared to MDA-MB-231
      cells under similar voltages. CONCLUSION: Our study provides an economical and
      efficient method of studying electrophoretic and electrokinetic phenomenon of
      different cell types that can be used to the advantage of detecting and
      monitoring cancer progression.

PMID- 30275195
TI  - Increased Soluble PD-L1 Levels in the Plasma of Patients with Epithelial Ovarian
      Cancer Correlate with Plasma Levels of miR34a and miR200.
AB  - BACKGROUND: Recently, programmed cell death protein 1 (PD1) blocking and anti
      programmed death-ligand 1 (PD-L1) agents were approved for the treatment of
      various human malignancies. MATERIALS AND METHODS: Our study examined the
      expression of PD-L1 in neoplastic tissue (17 patients) and the plasma soluble
      (s)PD-L1 of 32 patients with ovarian carcinoma, in parallel with the levels of
      specific microRNAs (miRs), using immunohistochemistry, enzyme-linked
      immunosorbent assay (ELISA) and real-time quantitative reverse transcription
      polymerase chain reaction (qRT-PCR), respectively. RESULTS: PD-L1 levels were
      significantly higher in the plasma of patients with ovarian cancer compared to
      healthy women (p=0.01). High miR200 levels were related to high sPD-L1 levels
      (p=0.03), whilst high miR34a levels were associated with low sPD-L1 levels
      (p=0.02). Immunohistochemical expression of PD-L1 by cancer cells was not related
      to plasma miR levels, nor to the level of sPD-L1. CONCLUSION: As well as cancer
      cell expression of PD-L1, a high sPD-L1 level characterizes a subset of patients
      with ovarian cancer. The value of this latter feature as a biomarker for the
      administration of anti-PD-L1/PD1 therapy needs further evaluation. Micro-RNAs,
      such as miR34a and miR200, may have a role in the efficacy of immunotherapy.

PMID- 30275196
TI  - Up-regulation of Bone Morphogenetic Protein 7 by 2-Hydroxycinnamaldehyde
      Attenuates HNSCC Cell Invasion.
AB  - BACKGROUND/AIM: Few studies have examined the effect of 2'-hydroxycinnamaldehyde
      (HCA) on head and neck squamous cell carcinoma (HNSCC) cell invasion. This study
      examined the role of BMP7 on the anti-migration and anti-invasion activity of HCA
      using HNSCC cells. MATERIALS AND METHODS: Matrigel invasion and wound healing
      assays were conducted to investigate cell migration or invasion. BMP7
      overexpression vector or siRNA mixture was used for transient regulation of gene
      expression. RESULTS: HCA attenuated HNSCC cell migration and spheroids Matrigel
      invasion without cytotoxicity. mRNA and protein expression of BMP7 increased with
      HCA treatment. Exogenous BMP7 overexpression without HCA treatment attenuated
      Matrigel invasion of cells. Furthermore, suppression of BMP7 by siRNA alleviated
      the inhibitory effect of HCA on the invasion of Matrigel by the cell, indicating
      that BMP7 is responsible for the anti-migration effect of HCA in HNSCC cells.
      CONCLUSION: HCA treatment led to a remarkable up-regulation of BMP7, which
      resulted in the attenuation of HNSCC cell invasion.

PMID- 30275197
TI  - Proteomic Identification of FLT3 and PCBP3 as Potential Prognostic Biomarkers for
      Pancreatic Cancer.
AB  - BACKGROUND/AIM: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest
      types of cancer, particularly due to its aggressive course and challenging
      diagnostics in early-stage disease. The aim of this study was to discover new
      potential prognostic and diagnostic pancreatic cancer biomarkers. MATERIALS AND
      METHODS: The proteomes of 37 samples from pancreatic cancer, inflammatory or
      healthy pancreatic tissue derived through in-depth differential proteomic
      analysis were compared. RESULTS: A set of candidate proteins as pancreatic cancer
      specific diagnostic or prognostic biomarkers were identified. Survival data of
      patients after two-year follow-up indicated FLT3 and PCBP3 proteins as potential
      biomarkers for favourable pancreatic cancer prognosis. The levels of PCBP3
      correlated with tumour stage and FLT3 levels, were evaluated as independent
      prognostic marker. CONCLUSION: FLT3 and PCBP3 represent potential biomarkers for
      improved individualized pancreatic cancer prognosis. Moreover, FLT3 may play a
      role in future treatment selection.

PMID- 30275198
TI  - X-ray as Irradiation Alternative for K562 Feeder Cell Inactivation in Human
      Natural Killer Cell Expansion.
AB  - BACKGROUND/AIM: gamma-Irradiation has been proven to be the most effective method
      to inactivate K562 cells, but gamma-irradiators are not available in some
      institutes. This study was designed to compare the effects of X-ray and gamma
      irradiation on K562 cells in natural killer (NK) cell expansion. MATERIALS AND
      METHODS: To expand NK cells, isolated peripheral blood mononuclear cells (PBMCs)
      were co-cultured with gamma-irradiated or X-ray-treated K562 cells plus IL-2 and
      IL-15. Characteristics of expanded NK cells were identified by flow cytometry.
      RESULTS: NK cell expansion rate tended be to lower in the X-ray-treated group
      (68.9+/-32.6) than the gamma-irradiated group (78+/-28.7), but the difference was
      not significant (p=0.39). Furthermore, NK cell functions or receptor expression
      were similar in the two groups. CONCLUSION: Our results suggest that X-ray
      treatment can be used as an alternative to gamma-irradiation for K562 cells
      inactivation in human NK cell expansion.

PMID- 30275200
TI  - High Efficacy of Intravenous Gimatecan on Human Tumor Xenografts.
AB  - BACKGROUND/AIM: The lipophilic, orally bioavailable camptothecin analogue
      gimatecan is characterized by improved efficacy over conventional camptothecins
      on human tumor xenografts. Gimatecan produced excellent outcomes orally with
      prolonged, low-dose, daily treatments. The aim of this study was to assess the
      antitumor efficacy of i.v. administered gimatecan. MATERIALS AND METHODS: The
      antitumor activity of gimatecan delivered i.v. q4dx4 was evaluated in nude mice
      bearing human tumors and compared to clinically available anticancer drugs.
      RESULTS: Intravenous administration of gimatecan showed superior efficacy with
      remarkable achievements at well tolerated doses. Moreover, prolonged treatments
      with i.v. administered gimatecan showed efficacy in models of cancer refractory
      to current therapeutic approaches, like an orthotopic brain tumor. CONCLUSION:
      Although the oral route is practical for gimatecan administration, the results
      support the interest in developing a suitable i.v. formulation in an attempt to
      further exploit the therapeutic potential of the compound.

PMID- 30275199
TI  - Autophagic Gene Polymorphisms in Liquid Biopsies and Outcome of Patients with
      Metastatic Clear Cell Renal Cell Carcinoma.
AB  - BACKGROUND/AIM: Autophagy has been shown to be involved in cancer development and
      response to cancer therapy. In this study, genotypes of autophagic genes were
      analyzed to assess their correlation with the risk of clear cell renal cell
      carcinoma (ccRCC) and the outcome of patients treated with pazopanib for
      metastatic ccRCC. MATERIALS AND METHODS: Single nucleotide polymorphisms
      (SNPs)were selected in the following genes: ATG4A (rs7880351), ATG4B (rs6709768),
      ATG4C (rs2886770, rs6670694, rs6683832), ATG5 (rs9373839, rs3804333, rs490010),
      ATG16L1 (rs6752107), ATG16L2 (rs10751215) and IRGM (rs10059011). The Kaplan-Meier
      method and log-rank test were used to evaluate differences between groups.
      RESULTS: Forty patients with metastatic ccRCC treated with pazopanib were
      included in the analysis. ATG16L2rs10751215 was significantly less frequent in
      patients with ccRCC compared to the general population, suggesting its potential
      protective role, while ATG4Ars7880351, ATG4C rs6670694 and rs6683832 and ATG5
      rs490010 were correlated with the progression-free survival (PFS) of patients
      treated with pazopanib. CONCLUSION: Our results suggest, for the first time, that
      autophagic gene SNPs are associated with ccRCC risk and patient outcome.

PMID- 30275201
TI  - Kisspeptin Inhibits Colorectal Cancer Cell Invasiveness by Activating PKR and
      PP2A.
AB  - BACKGROUND/AIM: The aim of the present study was to investigate the mechanism
      through which kisspeptin inhibits colorectal cancer metastasis. MATERIALS AND
      METHODS: Colorectal cancer cells were treated with kisspeptin and then subjected
      to assays for cell viability, migration, invasion and anchorage-independent
      growth. Kisspeptin receptor (KISS1R) requirement was examined by siRNA-based gene
      silencing followed by western blot and invasion assays. Kisspeptin regulation of
      PKR and PP2A was examined by treating cells with inhibitors for PKR or PP2A.
      RESULTS: Kisspeptin inhibited colorectal cancer cell invasiveness without
      affecting cell proliferation. Kisspeptin required activation of KISS1R and
      resulted in activation of PKR and PP2A. PKR inhibitor blocked kisspeptin-induced
      PP2A phosphorylation, while PP2A inhibitor failed to block kisspeptin-induced PKR
      phosphorylation. CONCLUSION: Kisspeptin-mediated activation of PKR-PP2A inhibited
      colorectal cancer cell invasiveness.

PMID- 30275202
TI  - 4-Methylumbelliferone Decreases the Hyaluronan-rich Extracellular Matrix and
      Increases the Effectiveness of 5-Fluorouracil.
AB  - BACKGROUND/AIM: Pancreatic cancer responds poorly to most chemotherapeutic
      agents. Several studies have reported that hyaluronan (HA)-rich extracellular
      matrix (ECM) is a biological barrier against chemotherapeutic agents. 4
      methylumbelliforone (MU) led to inhibition of HA synthesis and its preservation
      in ECM, which may enhance 5-fluorouracil (5-FU) cytotoxicity. Thus, new therapy
      with MU and 5-FU may be developed for pancreatic cancer. MATERIALS AND METHODS: A
      5-fluorouracil (5-FU) concentration and 4-methylumbelliferone (MU) dosage was
      analyzed by high-performance liquid chromatography (HPLC). Change in antitumor
      efficacy of 5-FU in combination with MU was also examined in vivo and in vitro.
      RESULTS: Combined 5-FU and MU treatment inhibited cell proliferation better than
      5-FU alone; 0.01 mM 5-FU alone decreased cell proliferation by 37.7 %, while 0.01
      mM 5-FU with 0.5 mM MU decreased cell proliferation by 57.4%. MU enhanced the
      intracellular concentration of 5-FU by 47.3% compared to control. Mice tumors
      treated with 5-FU and MU decreased in size and animal survival was prolonged.
      Moreover, MU decreased cohesiveness of the intercellular space. CONCLUSION:
      Combination therapy of 5-FU with MU was effective. A novel therapy can be
      designed for pancreatic cancer by using ECM modulation.

PMID- 30275203
TI  - Comparative p16IKN4A Expression in Laryngeal Carcinoma and Cervical Cancer
      Precursors: A Real-time Grid-based Immunocytochemistry Analysis.
AB  - BACKGROUND/AIM: p16 (gene locus: 9p21) tumor suppressor gene is considered an
      important biomarker for the progression and prognosis in a variety of
      malignancies and pre-cancerous lesions, including high-risk (HR-) human papilloma
      virus (HPV)-mediated squamous intraepithelial lesions (SILs), based on
      cytological and the corresponding cervical intraepithelial neoplasia (CIN)
      histopathological categorization. p16 acts as a cyclin-dependent kinase-4
      inhibitor negatively regulating the cell cycle. In persistent HPV infection, E7
      oncogenic protein binds retinoblastoma protein leading to its proteolytic
      transformation, also triggering E2F dissociation, which increases DNA
      transcription and progression to S phase. This mechanism promotes aberrant p16
      over-expression. Our aim was to comparatively analyze p16 protein expression
      patterns in laryngeal squamous cell carcinomas (LSCC) and also in SILs. MATERIALS
      AND METHODS: Fifty (n=50) primary LSCCs tissues all non-HPV-dependent, and a set
      of 50 liquid-based SILs, were analyzed by immunohistochemistry and
      immunocytochemistry, respectively. Concerning the screening process in
      cytological slides, a novel real-time reference and calibration grid platform was
      implemented and employed. RESULTS: Decreased protein expression was observed in
      34/50 (68%) tissues regarding LSCCs. Overall p16 expression was associated to
      smoking status of the patients (p=0.001), and also with the p-stage of the
      examined malignancies (p=0.033). A strong statistical significance was assessed
      correlating LSIL/HSIL cases with a progressive p16 over expression (p=0.001),
      also reflecting a higher CIN diagnosis (p=0.001). CONCLUSION: p16 down-regulation
      is a frequent genetic event in LSCCs, which is associated with advanced disease.
      In contrast to this, p16 over-expression triggered by a specific molecular
      mechanism shows a strong relationship with a progressively aggressive phenotype
      due to upgraded SIL/CIN cervical categorization. The first described application
      of the grid platform demonstrated a considerable improvement in the
      immunocytochemistry slide screening process enhancing the diagnostic reliability.

PMID- 30275204
TI  - Hard Palate Melanoma: A Population-based Analysis of Epidemiology and Survival
      Outcomes.
AB  - BACKGROUND/AIM: Hard palate melanoma is an extremely rare and aggressive tumor
      arising from the mucosal epithelium of the oral cavity. The aim of this study was
      to analyze epidemiology, loco-regional treatment patterns and survival outcomes
      of this disease. MATERIALS AND METHODS: The National Cancer Institute's
      Surveillance Epidemiology and End Results (SEER) database was searched for all
      cases of hard palate melanoma diagnosed between 1973 and 2012. The Kaplan-Meier
      method was used to calculate overall survival rate, log-rank test to compare
      survivals of different subgroups, and Cox hazard regression analysis to determine
      independent predictors of overall survival. RESULTS: Overall, 83 patients were
      identified, 49 female and 34 males. The distribution among ages was: 13.3% <50
      years, 38.6% between 50 and 69 years, 48.2% >=70. Surgery alone was applied in
      48.2% of patients, radiation therapy alone in 6%, and combination of surgery and
      radiation therapy in 33.7%. Overall 5-year survival was 26.3%. Survival with
      adjuvant radiation therapy was not longer than with surgery alone. CONCLUSION:
      Hard palate melanoma is a rare malignancy mostly affecting the elderly, with low
      overall survival. The main treatment is surgical resection, while adjuvant
      radiotherapy does not improve survival. The establishment of an international
      registry is warranted to better define treatment options.

PMID- 30275205
TI  - De Novo Myelodysplastic Syndrome and Subsequent Diagnosis of Primary Solid
      Tumors: Evidence from the National Cancer Institute 2001-2011.
AB  - BACKGROUND: To our knowledge there are no population-level studies on the
      association between non-treatment-related myelodysplastic syndrome (MDS) and
      subsequent primary solid tumors. MATERIALS AND METHODS: Adult patients diagnosed
      with non-treatment-related MDS were selected from the SEER 18 database and the
      risk of subsequent primary solid tumor was calculated. RESULTS: A total of 40,780
      patients with a diagnosis of MDS were reported in the SEER 18 registry during
      2001 to 2011. In these patients, 2,111 subsequent primary solid tumors were
      diagnosed with an observed/expected (O/E) ratio of 1.16 and an absolute excess
      risk of 26.86 per 10,000. Diagnosis of subsequent solid tumor was most likely
      immediately after diagnosis of MDS or within 1 year of diagnosis. CONCLUSION: The
      risk of diagnosis of primary solid tumor malignancy in adult patients with de
      novo MDS is significantly higher compared to the general population. It is
      unclear whether this is due to detection bias or underlying pathophysiology.

PMID- 30275206
TI  - Suboptimal Outcomes in Cutaneous Squamous Cell Cancer of the Head and Neck with
      Nodal Metastases.
AB  - BACKGROUND/AIM: There are limited data regarding survival, failure patterns, and
      factors associated with disease recurrence in patients with cutaneous squamous
      cell cancer of the head and neck (cSCC-HN) with nodal metastases. PATIENTS AND
      METHODS: A retrospective analysis of patients with cSCC-HN metastatic to cervical
      and/or parotid lymph nodes treated with surgery and post-operative radiation
      therapy was performed. RESULTS: This study included 76 patients (57
      immunocompetent and 18 immunosuppressed) with a median follow-up of 18 months.
      Overall survival, disease-free survival (DFS), and disease recurrence (DR) at 2
      years was 60%, 49%, and 40%, respectively. Immunosuppressed patients had
      significantly lower 2-year DFS (28% vs. 55%; p=0.003) and higher DR (61% vs. 34%;
      p=0.04) compared to immunocompetent patients. Analysis of immunocompetent
      patients demonstrated extracapsular extension (ECE) as the only factor associated
      with DR (p<0.0001). CONCLUSION: Patients with nodal metastases from cSCC-HN have
      suboptimal outcomes. ECE and immunosuppression were significantly associated with
      DR.

PMID- 30275207
TI  - Report of Objective Clinical Responses of Cancer Patients to Pharmaceutical-grade
      Synthetic Cannabidiol.
AB  - BACKGROUND/AIM: Cannabinoids are widely used in the management of pain, nausea
      and cachexia in cancer patients. However, there has been no objective clinical
      evidence of any anticancer activity yet. The aim of this study was to assess the
      effects of pharmaceutical-grade synthetic cannabidiol on a range of cancer
      patients. PATIENTS AND METHODS: We analysed the data routinely collected, as part
      of our treatment program, in 119 cancer patients over a four-year period.
      RESULTS: Clinical responses were seen in 92% of the 119 cases with solid tumours
      including a reduction in circulating tumour cells in many cases and in other
      cases, a reduction in tumour size, as shown by repeat scans. No side-effects of
      any kind were observed when using pharmaceutical grade synthetic cannabidiol.
      CONCLUSION: Pharmaceutical-grade synthetic cannabidiol is a candidate for
      treating breast cancer and glioma patients.

PMID- 30275208
TI  - Roux-en-Y Plus Distal Jejunal Pouch After Total Gastrectomy: A Prospective Study.
AB  - BACKGROUND/AIM: We previously described the safety of distal jejunal pouch with
      Roux-en-Y reconstruction after total gastrectomy. The present prospective study
      evaluated its clinical benefit. PATIENTS AND METHODS: Forty-five patients with
      gastric cancer were preoperatively assigned to groups who underwent Roux-en-Y
      reconstruction with jejunal pouch (PRY) (n=23) or without pouch (RY) (n=22). Age,
      sex, grade of lymph node dissection, splenectomy and mode of laparotomy were
      analyzed, and body mass index (BMI), volume of food intake at one sitting and
      blood chemistry (total protein, hemoglobin, iron and cholesterol) were
      periodically assessed in both groups. RESULTS: Post-surgical mortality and severe
      morbidity did not occur. Three and four patients in the PRY and RY groups,
      respectively, died of gastric cancer recurrence during the study. BMI at six
      months after surgery was significantly higher in the PRY than in the RY group
      (p<0.05). The percentage of food intake at one year after the procedure was
      significantly higher in the PRY than in the RY group (p<0.05). CONCLUSION: The
      distal jejunal pouch ameliorated postoperative weight loss and increased food
      intake. A distal jejunal pouch with PRY reconstruction may confer significant
      clinical advantages after total gastrectomy. The long-term clinical benefit of
      this procedure should be evaluated.

PMID- 30275209
TI  - Cholangiocarcinoma: CT-guided High-Dose Rate Brachytherapy (CT-HDRBT) for Limited
      (<4 cm) and Large (>4 cm) Tumors.
AB  - BACKGROUND/AIM: Thermal-ablative therapies are limited to tumors of 3-4 cm
      diameter. The purpose of this study was to evaluate the local tumor control (LTC)
      of CT-guided High-Dose-Rate-Brachytherapy (CT-HDRBT) for ablation of
      cholangiocarcinomas (CCA) >=4 cm compared to smaller tumors. PATIENTS AND
      METHODS: Sixty-one patients (tumors: 142, interventions: 91) were treated from
      March 2008 to January 2017. LTC, progression-free survival (PFS) and overall
      survival (OS) after first CT-HDRBT were identified for two subgroups (A:<4 cm,
      B:>=4 cm) and the influence of coverage and target-dose were evaluated. Log-Rank-
      and Mann-Whitney-U-Tests were performed for statistical analyses with p-values
      <0.05 considered as significant. RESULTS: Better coverage was achieved for
      smaller tumors (A: 99.22-0.25%, B: 95.10-1.40%, p<0.001). LTC was better in
      subgroup A (A: 8, B: 6 months, p=0.006). Larger tumors (4-7 cm) with incomplete
      coverage showed the poorest LTC (p=0.032). There were no statistical
      significances in PFS (A: 5, B: 3 months, p=0.597) and OS (A:15.5; B:10.0 months,
      p=0.107). CONCLUSION: CT-HDRBT is sufficient in CCA >=4 cm, if full coverage with
      therapeutic doses can be achieved.

PMID- 30275210
TI  - Impact of Body Mass Index (BMI) on Chemotherapy-associated Toxicity in Ovarian
      Cancer Patients. A Pooled Analysis of the North-Eastern German Society of
      Gynecological Oncology (NOGGO) Databank on 1,213 Patients.
AB  - BACKGROUND/AIM: Chemotherapy-associated toxicity is one of the limiting factors
      regarding treatment efficacy, patient outcome and quality of life in this
      collective. Underweight or obese patients represent a major group in which the
      therapy seems to be more challenging. The aim of this analysis was to evaluate
      the impact of BMI on the toxicity in patients undergoing chemotherapy. PATIENTS
      AND METHODS: The data of three prospective phase II/III studies ('Tower',
      'Topotecan phase III' and 'Hector') of the North-Eastern German Society of
      Gynecological Oncology including 1,213 patients with recurrent ovarian cancer
      were retrospectively analyzed. The study was performed using logistic regression
      and Cox regression analysis. RESULTS: The median age at diagnosis was 59 years.
      Sixty-seven (5.5%) patients had BMI <20 and 272 (22.4%) patients had BMI >30.
      Preterm termination of the chemotherapy was associated with lower BMI (p=0.017).
      Moreover, non-hematological toxicity grade III/IV was mainly observed in
      underweighted women as well (p<0.001). Patients with higher BMI more often
      presented with grade III/IV anemia (p=0.019) and as a consequence required blood
      transfusions more frequently (p=0.005). The overweight group was also associated
      with a higher number of co-medications. However, no difference in survival
      regarding BMI was observed in our study. CONCLUSION: Fewer chemotherapy cycles
      and preterm discontinuation were more frequent in patients with lower BMI.
      Hematological toxicity and higher medication intake appeared more often in
      patients with higher BMI.

PMID- 30275211
TI  - Baseline Sarcopenia and Skeletal Muscle Loss During Chemotherapy Affect Survival
      Outcomes in Metastatic Gastric Cancer.
AB  - AIM: To determine the association between sarcopenia and prognosis in patients
      with metastatic gastric cancer (mGC) receiving chemotherapy. PATIENTS AND
      METHODS: Our study retrospectively evaluated 231 consecutive Japanese patients
      with mGC who commenced first-line chemotherapy at our Institution between January
      2013 and December 2015. Muscle loss during chemotherapy was defined as a >=10%
      reduction in the skeletal muscle index and was evaluated for its association with
      time to treatment failure (TTF) and overall survival (OS). RESULTS: Of 118
      patients, 89% had baseline sarcopenia and 31% developed muscle loss. Muscle loss
      was significantly associated with shorter TTF and OS and was an independent
      prognostic factor for both these parameters; poor performance status and poorer
      differentiation on histology were also significant predictors of shorter OS.
      However, muscle loss was not significantly associated with increased grade 3 or
      higher toxicities. CONCLUSION: Muscle loss during chemotherapy negatively
      affected survival among patients with mGC.

PMID- 30275212
TI  - Current and Future Use of Radiological Images in the Management of Gynecological
      Malignancies - A Survey of Practice in the UK.
AB  - BACKGROUND/AIM: Radiology provides increasingly accurate and complex information.
      Understanding the clinicians' interpretation of scans could improve surgical
      planning, decision-making; informed training and development of augmented
      imaging. This was a survey exploring the interpretation of imaging by clinicians
      and its use in operative preparation and prediction. MATERIALS AND METHODS: The
      survey was open for two-months and circulated online to British Gynaecological
      Cancer society members. RESULTS: Seventy-three (19%) members completed the
      survey. Respondents had a confidence level of 51% in their ability to interpret
      computed tomography (CT) and/or magnetic resonance imaging (MRI) images
      independently. Preoperative imaging was commonly used to plan operations, predict
      complications and complete resection. Images were reviewed for primary
      (96.3%)/interval (92.6%) ovarian debulking, but less so for vulvectomy (45%).
      Scan (79.6%) and multidisciplinary team meeting (MDT) (66.6%) reports were used
      more often than scan images (50%) for operative planning. Amount and pattern of
      disease on scan were the most important factors predicting operating time.
      CONCLUSION: Imaging influences the surgeon's planning, however respondents lack
      confidence. Training of clinicians in radiological interpretation needs to
      improve. Augmented image interfaces could facilitate this.

PMID- 30275214
TI  - Relationship Between CA 19.9 and the Lewis Phenotype: Options to Improve
      Diagnostic Efficiency.
AB  - BACKGROUND/AIM: Approximately 10% of patients are unable to synthesize CA 19.9
      (Lewis-negative), and these results are erroneously considered false-negatives.
      The aim of this study was to confirm that CA 19.9 cannot be detected by
      immunoassays in Lewis-negative patients. MATERIALS AND METHODS: CA 19.9 levels
      were measured by immunological assays and Lewis phenotype was determined by the
      haemagglutination reaction. RESULTS: Patients with Lewis phenotype (a+b-) or (a
      b+) had significantly higher CA 19.9 levels than Lewis-negative patients with
      active cancer (p<0.001), no-evidence of disease (NED) patients (p<0.001) or
      patients with benign disease (p<0.001). Ninenty-four percent of patients (33/35)
      with undetectable CA 19.9 had a Lewis-negative phenotype. Additionally, 94.7%
      (34/36) of patients with Lewis-negative phenotypes had undetectable CA 19.9 serum
      levels. CONCLUSION: Patients with undetectable CA 19.9 serum levels tend to be
      Lewis-negative, and CA 19.9 is not useful in diagnosis or follow-up.

PMID- 30275213
TI  - Different Timing to Use Bevacizumab in Patients with Recurrent Glioblastoma:
      Early Versus Delayed Administration.
AB  - BACKGROUND/AIM: In patients with recurrent glioblastoma, the best timing to
      administer bevacizumab is not well addressed yet. In this study, we reported the
      results of a monocentric experience comparing the early use of bevacizumab
      (following the first GBM recurrence) with the delayed administration (following
      the second or even further GBM recurrences). MATERIALS AND METHODS: This analysis
      included 129 glioblastoma patients with a median follow-up of 22.4 months
      (range=5.26-192 months). RESULTS: The median time lapse from diagnosis of
      glioblastoma to disease recurrence was 11.6 months; 13.1 for patients treated
      with deferred administration of bevacizumab and 9.9 for patients with early
      administration (p=0.047). Bevacizumab progression-free survival with early and
      delayed use was 3.45 and 2.92 months, respectively (p=0.504). Survival time from
      the start of bevacizumab was 6.18 months in patients with early administration,
      and 6.47 in the delayed administration one (p=0.318). CONCLUSION: Delayed
      administration of bevacizumab can be considered in selected patients with less
      aggressive recurrent glioblastoma.

PMID- 30275215
TI  - Prognostic Significance and Clinicopathological Features of Synchronous
      Colorectal Cancer.
AB  - AIM: This study aimed to clarify the difference in the clinicopathological and
      prognostic features between synchronous colorectal cancer (CRC) and solitary CRC.
      MATERIALS AND METHODS: A retrospective analysis was conducted in patients with
      synchronous and solitary CRC. RESULTS: A total of 92 (7.1%) out of 1,295
      consecutive patients had synchronous CRC. Mucinous adenocarcinoma was more
      frequent in patients with synchronous CRC than in those with solitary CRC (13.0%
      vs. 3.7%; p<0.001). The 5-year relapse-free survival (RFS) rate was poorer in
      patients with synchronous CRC than in those with solitary CRC (65.3% vs. 75.1%;
      p=0.035), which was contrived by the multivariate analysis (hazard
      ratio=1.52(HR); p=0.039). CONCLUSION: Patients with synchronous CRC had a poorer
      RFS than those with solitary CRC; thus, patients with synchronous CRC might
      require more intensive care than those with solitary CRC in follow-up.

PMID- 30275216
TI  - PD-L2 Expression as a Potential Predictive Biomarker for the Response to Anti-PD
      1 Drugs in Patients with Non-small Cell Lung Cancer.
AB  - BACKGROUND/AIM: To investigate the role of programmed cell death-ligand 2 (PD-L2)
      expression as a predictive biomarker for response to anti-programmed cell death-1
      (PD-1) drugs in patients with non-small cell lung cancer (NSCLC). PATIENTS AND
      METHODS: Ten patients who had undergone curative lung resection and received the
      anti-PD-1 drugs for the recurrence were enrolled. The cut-off value for PD-L2
      (antibody clone 176611) expression on tumor cells was set at 50%. Tumor response
      was evaluated according to immune-related response criteria. RESULTS: Seven
      patients (70.0%) were positive for PD-L2. The response rates were 28.6% (2/7) and
      33.3% (1/3) in patients with PD-L2-positive and PD-L2-negative NSCLC,
      respectively. Disease control was obtained in 2 patients despite the programmed
      cell death-ligand 1 (PD-L1)-negativity (antibody clone 22C3: 0%, antibody clone
      SP142: 0%), and these tumors expressed PD-L2 (>=1%). CONCLUSION: PD-L2 expression
      may be a target of immunotherapy in patients with PD-L1-negative NSCLC.

PMID- 30275217
TI  - Prognostic Impact of PD-L2 Expression and Association with PD-L1 in Patients with
      Small-cell Lung Cancer.
AB  - BACKGROUND/AIM: Although some previous studies suggested that programmed cell
      death-ligand 1 (PD-L1) expression was significantly associated with a favorable
      postoperative prognosis in patients with small-cell lung cancer (SCLC), the
      prognostic significance of PD-L2 expression remains unknown. The aim of the
      current study was to investigate the prognostic significance of PD-L2 expression
      in patients with SCLC. PATIENTS AND METHODS: Thirty-eight patients who underwent
      resection of SCLC were analyzed. A monoclonal anti-human PD-L1 antibody (clone
      SP142) and a monoclonal anti-human PD-L2 antibody (clone 176611) were used as the
      primary antibodies. Cut-off value for PD-L1 and PD-L2 expression was set to 1%.
      RESULTS: Among 38 patients, 15 (39.5%) were positive for PD-L2 expression. No
      significant associations between PD-L2-positivity and clinicopathological
      factors, including PD-L1 positivity or prognosis were identified. No significant
      differences in disease-free survival and overall survival were observed between
      PD-L2-positive patients and PD-L2-negative patients (p=0.367 and p=0.726,
      respectively). CONCLUSION: PD-L2 expression is not related to clinicopathological
      factors or postoperative prognosis in patients with SCLC, though this should be
      further investigated in studies involving larger populations.

PMID- 30275218
TI  - SUVmax-based Parameters of FDG-PET/CT Reliably Predict Pathologic Complete
      Response After Preoperative Hyperthermo-chemoradiotherapy in Rectal Cancer.
AB  - BACKGROUND/AIM: To determine the most reliable predictor for pathologic complete
      response (pCR) in patients who underwent preoperative chemoradiotherapy and
      regional hyperthermia (HCRT) for rectal cancer. PATIENTS AND METHODS: Thirty-six
      patients were enrolled. The local control status of the patients was assessed
      using 18F-fluorodeoxyglucose positron emission tomography/computed tomography
      (FDG-PET/CT), magnetic resonance imaging (MRI), and colonoscopy before and after
      HCRT. The relationships between various parameters of these clinical examinations
      and pCR were analyzed. RESULTS: Ten (28%) patients achieved pCR. The accuracies
      of predicting pCR using FDG-PET/CT, MRI, and colonoscopy were 78%, 61%, and 75%,
      respectively. FDG-PET/CT was the only independent predictive modality for pCR
      (p=0.021). The maximum standardized uptake value (SUVmax) and SUVmax normalized
      to liver uptake (SLR) after HCRT showed the highest sensitivity (90%) and the
      decreasing rate of SUVmax and SLR demonstrated the highest specificity (89%) for
      pCR. CONCLUSION: SUVmax-based parameters of FDG-PET/CT after HCRT were the most
      reliable predictors for pCR.

PMID- 30275219
TI  - Long-term Survival and Propensity Score Matched Outcomes of Bilateral vs.
      Unilateral Diaphragm Interventions in Cytoreductive Surgery plus Intra-peritoneal
      Chemotherapy.
AB  - BACKGROUND/AIM: To assess the impact of short- and long-term outcomes of
      bilateral vs. unilateral diaphragm interventions in cyto-reductive surgery (CRS)
      and intra-peritoneal chemotherapy (IPC). PATIENTS AND METHODS: A total of 652
      CRS/IPC procedures, between 1996 and 2018, required diaphragm interventions.
      Among these, 388 underwent bilateral intervention. Preoperative heterogeneity was
      assessed in 6 parameters and addressed with propensity score matching. The
      association of each respective analysis was assessed with 11 outcomes. Overall
      survival was assessed based on histology. RESULTS: CRS/IPC requiring bilateral
      diaphragmatic interventions illustrated significantly increased operative hours
      (9.6 vs. 8.6 hours, p<0.001). Postoperatively, there was significantly increased
      red blood cell (RBC) transfusion (6.37 units vs. 4.47 units, p=0.007) and grade
      III and IV complications (57.3% vs. 40.6%, p=0.004). No difference was noted in
      ICU stay, total length of stay, hospital death and return to OT. In terms of
      respiratory complications, an increased incidence of pneumothorax (16.5% vs.
      6.2%, p<0.001) was noted whilst pleural effusions and pneumonia occurrences were
      non-significant. Overall survival, revealed bilateral interventions in low-grade
      appendiceal mucinous neoplasm conferred an increased relative risk (p=0.037,
      RR=2.230, 95%CI=1.052-4.730). They did not have an effect on OS in colorectal
      cancer and mesothelioma. CONCLUSION: Despite the increase in short-term
      morbidity, bilateral diaphragm interventions resulted in similar long-term
      survival to unilateral interventions.

PMID- 30275220
TI  - Detection of KK-LC-1 Protein, a Cancer/Testis Antigen, in Patients with Breast
      Cancer.
AB  - BACKGROUND: Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis
      antigen and predominant target for cancer immunotherapy. Its detection is only
      established based on gene expression. In this study, we established a monoclonal
      antibody against KK-LC-1 to detect its protein expression in formalin-fixed
      samples. MATERIALS AND METHODS: The monoclonal antibody against KK-LC-1 was
      evaluated and the detection of KK-LC-1 between gene expression and protein
      expression was compared in patients with breast cancer. The monoclonal antibody
      clone 34B3, which we established, stained testicular germ cells positively.
      RESULTS: The rates of detection of KK-LC-1 gene and protein expression were 11.8%
      and 52.9%, respectively. Protein expression was detected in all triple-negative
      breast cancer cases studied (n=8). Furthermore, KK-LC-1 was detected in all
      tumours without oestrogen receptor expression. CONCLUSION: This study indicated
      that KK-LC-1 expression was detected in breast cancer, especially in oestrogen
      receptor-negative subtypes.

PMID- 30275221
TI  - Serum DHEA-S Is a Predictive Parameter of Abiraterone Acetate in Patients with
      Castration-resistant Prostate Cancer.
AB  - BACKGROUND/AIM: There is no definitive biomarker that predicts the effectiveness
      of abiraterone acetate. The objective of this study was to investigate whether
      dehydroepiandrosterone sulfate (DHEA-S) predicts the effectiveness of abiraterone
      acetate. MATERIALS AND METHODS: This study included a total of 28 consecutive
      patients. The optimal cutoff value of DHEA-S for predicting the PSA response was
      calculated by receiver operating characteristic (ROC) analysis. The Cox
      proportional hazards model was performed to determine the predictive factors for
      the susceptibility to abiraterone acetate. RESULTS: Serum DHEA-S at baseline
      intercorrelated with the PSA response (correlation coefficient: -0.516). The
      optimal cutoff value of serum DHEA-S at baseline was 47.4 ug/dl in predicting
      >50% PSA decline. Serum PSA and serum DHEA-S at baseline were identified as
      significant factors for predicting PSA progression-free survival (p=0.010 and
      p=0.003, respectively). CONCLUSION: Serum DHEA-S at baseline may be a biomarker
      for predicting the prognosis of CRPC patients treated with abiraterone acetate.

PMID- 30275222
TI  - Preexisting Interstitial Lung Disease and Lung Injury Associated with Irinotecan
      in Patients with Neoplasms.
AB  - BACKGROUND/AIM: The aim of this study was to reveal risk factors for lung injury
      following irinotecan administration for the treatment of neoplasms. PATIENTS AND
      METHODS: This study included 204 patients who received irinotecan from October
      2005 to November 2014 and had evaluable chest CT images before initiation of
      irinotecan. RESULTS: Six (2.9%) patients developed lung injury and, of these, 2
      had preexisting interstitial lung disease (pre-ILD). The frequency of lung injury
      in patients with pre-ILD was 11% (2 of 19) while that in patients without pre-ILD
      was 2.2%. Risk factor analysis for the lung injury showed pre-ILD was the most
      predictable factor [odds ratio (OR) 5.00, p=0.07]. Combination with other agents,
      origin of neoplasms (lung or not), initial dose or minimum interval were not
      observed to be related to risk. CONCLUSION: The risk of lung injury with
      irinotecan was high when pre-ILD was present and the risk was comparable with
      previously reported other agents.

PMID- 30275223
TI  - Cisplatin Substitution with Carboplatin During Radical Chemoradiotherapy for
      Oesophagogastric Carcinoma: Outcomes from a Tertiary Centre.
AB  - BACKGROUND/AIM: Cisplatin-based radical chemoradiotherapy (CRT) is utilised in
      oesophagogastric (OG) cancer but the toxicity profile of cisplatin limits its
      use. This study aimed to evaluate the clinical characteristics and outcomes of
      patients treated with either cisplatin or carboplatin based CRT at our
      institution. MATERIALS AND METHODS: This is a retrospective analysis of patients
      with localised OG cancer undergoing CRT with cisplatin/fluoropyrimidine (CX/F) or
      carboplatin/fluoropyrimidine (CarboX/F) between January 2001 and December 2014.
      RESULTS: A total of 91 eligible patients were included. Median age was 65 years
      (IQR=57-75) for CX/F and 77 years (IQR=69-80) for CarboX/F. Adenocarcinoma
      histology and Charlson comorbidity index were higher in the CarboX/F group.
      Endoscopic complete response (CR) was achieved in 64% of CX/F group and 48% of
      CarboX/F group (p=0.19). The median PFS for CX/F was 31.0 months (95%CI=18.2-NE)
      vs. 18.7 months for CarboX/F (95%CI=13.5-30.4; HR=1.49, p=0.21). CONCLUSION:
      Despite significant differences in baseline clinical characteristics, patients
      treated with carboplatin CRT demonstrated no significant difference in PFS or
      endoscopic CR rate, compared to those treated with cisplatin.

PMID- 30275224
TI  - Radiation Dose Escalation in Accelerated Hyperfractionated Radiotherapy for Stage
      III Non-small-cell Lung Cancer.
AB  - AIM: To identify clinical benefits of dose escalation in accelerated
      hyperfractionated radiotherapy (AH-RT) for stage III non-small-cell lung cancer
      (NSCLC) using propensity score-matched (PSM) analysis. MATERIALS AND METHODS: Our
      study retrospectively examined 294 patients undergoing definitive radiotherapy
      [131 patients, conventional once-daily radiotherapy (OD-RT); and 163, AH-RT] who
      were followed-up for a median of 40.4 months. The impact of overall survival
      (OS), progression-free survival (PFS), and locoregional control (LRC) was
      investigated. RESULTS: Pre-PSM, the median OS, PFS, and LRC durations were 23.1
      vs. 39.9 (p=0.03), 8.9 vs. 13.5 (p<0.01), and 12.9 vs. 50.3 (p<0.01) months in
      the OD-RT and AH-RT groups, respectively. After-PSM (two matched groups of 144
      patients), AH-RT was associated with better LRC [adjusted hazard ratio
      (aHR)=0.59, 95% confidence interval (CI)=0.33-0.99, p=0.04] and marginally better
      PFS (aHR=0.65, 95% CI=0.41-1.03; p=0.06), but not OS (aHR=0.75, 95% CI=0.46-1.24;
      p=0.26). CONCLUSION: After PSM analysis, dose escalation using AH-RT improved LRC
      and PFS in patients with locally advanced NSCLC. AH-RT can be a promising option
      for patients with advanced NSCLC.

PMID- 30275225
TI  - Long-term Follow-up Results of CT-guided Daily Adaptive Radiation Therapy for
      Localized Prostate Cancer.
AB  - BACKGROUND/AIM: To examine whether CT-guided daily adaptive radiation therapy
      (ART) can be safely administered against localized prostate cancer. PATIENTS AND
      METHODS: Twenty-six patients with localized prostate adenocarcinoma were
      irradiated through opposed AP/PA fields up to 46 Gy, then CT-guided daily ART was
      performed through opposed lateral fields until 76 Gy at 2 Gy/fraction. RESULTS:
      Biochemical relapse-free survival was 89% at 3 years and 85% at 5 years and 76%
      at 7 years after ART, respectively. The 3-, 5- and 7-year local relapse-free
      survival rates were 100%, 100% and 95%, respectively. The 5-year incidence rates
      of grade 1 and 2 late gastrointestinal adverse events were 15.4% (n=4) and 3.8%
      (n=1), respectively, and those of grade 1 and 2 late genitourinary adverse events
      were 3.8% (n=1) and 0% (n=0), respectively. CONCLUSION: CT-guided daily ART was
      well tolerated and suggested a good long-term tumor control with minimal adverse
      events.

PMID- 30275226
TI  - Bevacizumab-based Chemotherapy for Poorly-differentiated Neuroendocrine Tumors.
AB  - AIM: To assess and report the efficacy of and tolerance to bevacizumab-based
      chemotherapy in treatment outcome of metastatic poorly differentiated
      neuroendocrine tumors. PATIENTS AND METHODS: From 2007 to 2018, 11 consecutive
      patients with metastatic poorly differentiated neuroendocrine treated in first-
      or second-line with bevacizumab-based chemotherapies were included in this
      monocentric retrospective cohort. Tumor response was evaluated by computed
      tomographic scans. RESULTS: Administered treatment included 5-fluorouracil and
      irinotecan (FOLFIRI) bevacizumab, 5-fluorouracil and oxaliplatin (FOLFOX)
      bevacizumab and 5-fluorouracil, oxaliplatin and irinotecan (FOLFIRINOX)
      bevacizumab for four, two and five patients, respectively. Three were treated in
      first-line and eight in second-line after cisplatin-etoposide regimen. Using
      Response Evaluation Criteria in Solid Tumors, partial response was observed for
      seven patients, and stable disease for one patient, giving a response rate of
      63.6% (95% confidence interval=35.2-92.1%) and disease control rate of 72.7% (95%
      confidence interval=46.6-99.0%). All patients had died by the time of analysis,
      median progression-free survival was 14 months, and median overall survival was
      15.3 months. Observed toxicity with such protocols was classical with 10 grade 3
      4 toxic events, including three of hematological toxicity, three of infection,
      and three of digestive toxicity. CONCLUSION: Bevacizumab-based chemotherapy gave
      surprising efficacy and safety in first-or second-line treatment for metastatic
      poorly differentiated neuroendocrine tumor in this retrospective cohort.
      Prospective randomized trials of such therapy are warranted.

PMID- 30275227
TI  - Intraperitoneal Administration of Paclitaxel Followed by Paclitaxel, Cisplatin,
      and S-1 Chemotherapy for Cytology-positive Gastric Cancer: A Feasibility Study.
AB  - BACKGROUND/AIM: A preliminary study evaluating the feasibility of single
      intraperitoneal (IP) administration of paclitaxel followed by paclitaxel and
      cisplatin with S-1 (PCS) systemic chemotherapy for cytology-positive (CY1)
      gastric cancer. PATIENTS AND METHODS: Staging laparoscopy was performed to
      confirm CY1 and P0 status. Initially, patients received IP paclitaxel. Beginning
      7 days later PCS was given every 3 weeks followed by second-look laparoscopy.
      RESULTS: Nine patients were enrolled. The toxic effects of IP and systemic
      chemotherapy were acceptable. After chemotherapy, 8 patients converted from CY1P0
      to CY0P0 and 1 patient from CY1P0 to CY1P1. Gastrectomy was performed on 8
      patients except for the CY1P1 patient. Four patients were alive without
      recurrence. The 2-year overall and progression-free survival rates were 76% and
      65%, respectively. CONCLUSION: Combination chemotherapy with IP paclitaxel and
      sequential PCS is safe and may be effective for CY1 gastric cancer.

PMID- 30275228
TI  - Intraperitoneal and Systemic Chemotherapy for Patients with Gastric Cancer with
      Peritoneal Metastasis: A Phase II Trial.
AB  - AIM: To conduct a phase II study of single intraperitoneal (i.p.) administration
      of paclitaxel followed by paclitaxel, cisplatin, and S-1 (PCS) chemotherapy for
      patients with gastric cancer with peritoneal metastasis (PM). PATIENTS AND
      METHODS: Staging laparotomy was performed to confirm PM. Initially, patients
      received i.p. paclitaxel. Beginning 7 days later, PCS was given every 3 weeks
      followed by second-look laparoscopy. Primary and secondary endpoints were the
      overall survival (OS) rate, and response rate and patient safety, respectively.
      RESULTS: Seventeen patients were enrolled. The overall response rate was 70.5%
      (12/17). Grade 3/4 toxic effects included neutropenia and leukopenia. After
      chemotherapy, PM disappearance was confirmed in 11 patients. Gastrectomy was
      eventually performed in 11 patients. The 1-year OS rate was 82.4% and the median
      survival time was 23.9 months considering the overall cohort. CONCLUSION:
      Combination chemotherapy with i.p. paclitaxel and PCS is well tolerated and
      effective in patients with gastric cancer with PM.

PMID- 30275230
TI  - Investigation of Survivin Gene Polymorphism and Serum Survivin Levels in Patients
      with Brain Tumors.
AB  - BACKGROUND/AIM: The single nucleotide polymorphism -31C/G identified in the
      survivin gene promoter seems to be associated with over-expression of survivin,
      an anti-apoptotic protein. In gliomas, increased survivin expression correlated
      with decreased survival. The aim of the study was to investigate whether survivin
      gene polymorphism associates with benign and malignant brain tumors and whether
      it affects survivin serum levels. PATIENTS AND METHODS: Survivin polymorphism 
      31C>G was genotyped in 82 patients with brain tumors and 65 healthy controls by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and
      survivin levels were evaluated by enzyme-linked immuno sorbent assay (ELISA) in
      patients and controls. RESULTS: Serum survivin levels in patients with malignant
      tumors were higher than patients with benign tumors (p<0.001). Survivin levels in
      patients with malignant glial tumors and the frequency of the GG genotype were
      higher than in patients with benign tumors (p=0.04) and controls (p=0.05). The
      prevelance of the survivin gene promoter polymorphism -31C>G did not differ
      between patients and controls. CONCLUSION: Survivin promoter -31C>G gene
      polymorphism seems to be associated with serum survivin levels in brain tumors of
      different grades and histologies.

PMID- 30275229
TI  - EGFR, SMAD7, and TGFBR2 Polymorphisms Are Associated with Colorectal Cancer in
      Patients with Lynch Syndrome.
AB  - BACKGROUND/AIM: Epidermal growth factor receptor (EGFR), mothers against
      decapentaplegic homolog 7 (SMAD7) and transforming growth factor betta (TGFB) are
      crucial for colorectal cancer (CRC) tumorigenesis. This study investigated
      whether polymorphisms in EGFR, SMAD7, and TGFB are associated with CRC risk in
      patients with Lynch syndrome. MATERIALS AND METHODS: Genotyping was performed
      using Sequenom iPLEX MassArray. Association between genetic polymorphisms and CRC
      was assessed using a weighted Cox proportional hazard model. RESULTS: Patients
      carrying the AA genotype of EGFR rs2227983 had a significantly higher CRC risk
      than those carrying the G allele (HR=2.55, 95% CI=1.25-5.17). The dominant model
      of SMAD7 rs12953717 (CT + TT genotypes) significantly increased CRC risk
      (HR=2.17, 95% CI=1.12-4.16) when compared to the wild-type CC genotype.
      Similarly, the GG genotype of TGFBR2 rs6785358 significantly increased the risk
      of CRC (HR=21.1, 95% CI=5.06-88.1) compared to the AA genotype. CONCLUSION: EGFR,
      SMAD7, and TGFBR2 are associated with CRC risk in patients with Lynch syndrome.

PMID- 30275231
TI  - Foamy Histiocyte-like Esophageal Adenocarcinoma: Unusual Morphology and
      Diagnostic Pitfalls.
AB  - In the United States and other western countries, the vast majority of primary
      esophageal malignancies are adenocarcinomas arising in the lower esophagus within
      a background of Barrett's esophagus. The microscopic feature of esophageal
      adenocarcinoma varies, with the tubular or papillary adenocarcinoma of intestinal
      pattern being the most common, and other less common morphological patterns
      include adenosquamous, signet ring cell, mucinous, mucoepidermoid, and adenoid
      cystic carcinoma. This is a case report of esophageal adenocarcinoma with foamy
      histiocyte-like feature in a 71-year-old male with a history of smoking and
      Barrett's esophagus who presented with dysphagia and weight loss. The tumor cells
      showed an abundant foamy cytoplasm, low N/C ratio and irregular nuclear contour.
      They were arranged in single, trabecular and glandular patterns and deeply
      invaded adventitia. Lymphovascular invasion and perineural invasion were present.
      The foamy histiocyte like-tumor cells were negative for CD68, but strongly and
      diffusely positive for CK7. E-Cadherin was maintained in the tumor cells, and p53
      immunostaining revealed a wild-type staining pattern. To the best of our
      knowledge, this is the first documented case of primary esophageal adenocarcinoma
      with foamy-histiocyte-like phenotype. The clinical course, diagnosis and
      prognosis of this entity are discussed.

PMID- 30275232
TI  - Prominent Nucleoli and Non-glandular Feature Are Independent Predictors of PD-L1
      Expression in Lung Adenocarcinoma.
AB  - BACKGROUND/AIM: In patients with non-small cell lung cancer, relationships
      between PD-L1 (programmed death-ligand 1) expression and clinicopathological
      characteristics have been examined. However, the association between cytological
      features and PD-L1 expression remains unknown. Thus, the aim of this study was to
      investigate whether nuclear features might be correlated with PD-L1 expression in
      patients with advanced and inoperable lung adenocarcinoma using small biopsy
      specimens. MATERIALS AND METHODS: Archived slides from 90 patients with lung
      adenocarcinoma who underwent small biopsy between October 2014 and May 2017 at
      the Incheon St. Mary's Hospital, were reviewed. PD-L1 expression was detected by
      immunohistochemistry using PD-L1 22C3 IHC assay. Associations of PD-L1 expression
      with pathological and molecular features (EGFR mutation, ALK and ROS-1
      rearrangement) were statistically analyzed. RESULTS: PD-L1 expression in tumor
      cells was positive in 33 of 90 cases (36.7%). Higher PD-L1 expression (>=50%) was
      more frequent in cases with marked nuclear pleomorphism (p<0.001), coarse
      chromatin pattern (p=0.006), predominant nucleoli (>=3 MUm) (p<0.001), large
      nuclear diameter (>5* small lymphocyte) (p=0.006), non-glandular feature
      (p<0.001), and atypical mitosis (p=0.034). There were no significant correlations
      between PD-L1 positivity and molecular features. In multivariable logistic
      regression analysis, PD-L1 positivity was independently associated with prominent
      nucleoli (p=0.005) and non-glandular feature (p=0.007). CONCLUSION: Prominent
      nucleoli and non-glandular feature are independent predictors of PD-L1 expression
      in lung adenocarcinoma.

PMID- 30275233
TI  - Impact of CMV and EBV on Immune Recovery After Allogeneic Hematopoietic Cell
      Transplantation in Children.
AB  - BACKGROUND/AIM: Immune recovery is a key factor in the management of patients
      after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study
      analyzed the factors contributing to immune reconstitution after allo-HSCT.
      PATIENTS AND METHODS: Overall, 65 children with malignant or non-malignant
      diseases were included in multivariate analyses. RESULTS: The following factors
      contributed to a faster immune recovery: peripheral blood as a stem cell source
      and reactivation of CMV infection for CD3+ and CD4+ lymphocyte subpopulations;
      reactivation of CMV infection for CD8+ subset; donor EBV-IgG+ and no EBV
      reactivation for CD19 lymphocytes; recipient age below 10 years and peripheral
      blood as a stem cell source for NK cells. For CD2 and CD4/CD8 ratio no factor was
      significant in multivariate analysis. CONCLUSION: Patients receiving a graft from
      an EBV-IgG-positive donor and not having early EBV post-transplant viremia show
      faster recovery of the B-cells, while patients with early CMV-DNA-emia have a
      better re-establishment of T-cell subsets.

PMID- 30275234
TI  - A Phase I/II Study of NAC with Docetaxel, Cisplatin, and S-1 for Stage III
      Gastric Cancer.
AB  - BACKGROUND/AIM: The aim of this phase I/II study was to determine the safety, and
      efficacy of combination of neoadjuvant chemotherapy (NAC) with biweekly
      docetaxel, cisplatin, and S-1 (DCS) in stage III gastric cancer patients.
      PATIENTS AND METHODS: In the phase I study, S1 was administered at doses of 80
      mg/day to 120 mg/day depending on the body surface area and docetaxel was
      administered at 20 mg/m2, whereas cisplatin was initially administered at 25
      mg/m2 and was escalated by 5 mg/m2 up to 50 mg/m2 In the phase II study, safety
      and therapeutic efficacy of DCS were evaluated using the recommended dose of
      cisplatin. RESULTS: In phase I, 21 patients were enrolled. In level II,
      perforation of gastric cancer occurred in one case although no dose limiting
      toxicities (DLTs) were noted in level III-VI. Recommended dose for cisplatin was
      50 mg/m2/day. In phase II, among 47 patients, 14 experienced grade 3/4 adverse
      events. Clinically, response rate was 66.7% and disease control rate was 97.9%.
      The curative (R0) resection rate was 95.7%. Pathological response rate was 53.3%.
      Three-year overall survival and relapse-free survival rates were 78.5% and 65.3%,
      respectively. CONCLUSION: Biweekly DCS as NAC was efficient, safe, and
      acceptable; however, long-term survival should be evaluated to confirm the
      efficacy of biweekly DCS for stage III gastric cancer patients.

PMID- 30275236
TI  - Retraction.

PMID- 30275235
TI  - Profile and Outcome of Supraclavicular Metastases in Patients with Metastatic
      Breast Cancer: Discordance of Receptor Status Between Primary and Metastatic
      Site.
AB  - BACKGROUND: Breast cancer is a heterogenous and complex disease. A rare site of
      metastatic breast cancer disease is the neck. Data about supraclavicular
      metastases in patients with metastatic breast cancer are still lacking. Hence,
      our study aimed to analyze histological subtypes of supraclavicular metastases
      compared to the primary site. MATERIALS AND METHODS: This was a retrospective
      hospital-based cohort study of patients with breast cancer who developed
      supraclavicular metastases. Diagnosis of supraclavicular metastases was confirmed
      by biopsy or diagnostic lymph node extirpation. Histological subtypes were
      analyzed and Kaplan-Meier estimates were calculated for overall survival.
      RESULTS: A total of 20 patients were included in the analysis. The majority of
      the patients (12/20) had hormone receptor (HR)-positive/human epidermal growth
      factor receptor 2 (HER2)-negative supraclavicular metastases, disease in 3/20
      patients was HR-positive/HER2-positive, HR-negative/HER2-positive in 1/20
      patients and basal-like in 4/20 patients. Total discordance rates for estrogen
      receptor, progesterone receptor and HER2 between primary and metastatic tumors
      were 20.0%, 36.8% and 29.4%, respectively. The 5-year overall survival was 80%,
      whereas the 5-year survival after the onset of neck metastasis was 45%.
      CONCLUSION: As a rare site of metastatic breast cancer, supraclavicular
      metastases are associated with a worse median overall survival from their onset.
      The high rate of discordance of histological subtype stresses the necessity for
      biopsies in patients with supraclavicular metastasis.

PMID- 30275237
TI  - A Tool to Identify Adolescents at Risk of Cigarette Smoking Initiation.
AB  - : : media-1vid110.1542/5828318368001PEDS-VA_2017-3701Video Abstract OBJECTIVES:
      To describe the development of a prognostic tool to identify adolescents at risk
      for transitioning from never to ever smoking in the next year. METHODS: Data were
      drawn from the Nicotine Dependence in Teens study, a longitudinal investigation
      of adolescents (1999 to present). A total of 1294 students initially age 12 to 13
      years were recruited from seventh-grade classes in 10 high schools in Montreal.
      Self-report questionnaire data were collected every 3 months during the 10-month
      school year over 5 years (1999-2005) until participants completed high school (n
      = 20 cycles). Prognostic variables for inclusion in the multivariable analyses
      were selected from 58 candidate predictors describing sociodemographic
      characteristics, smoking habits of family and friends, lifestyle factors,
      personality traits, and mental health. Cigarette smoking initiation was defined
      as taking even 1 puff on a cigarette for the first time, as measured in a 3-month
      recall of cigarette use completed in each cycle. RESULTS: The cumulative
      incidence of cigarette smoking initiation was 16.3%. Data were partitioned into a
      training set for model-building and a testing set to evaluate the performance of
      the model. The final model included 12 variables (age, 4 worry or stress-related
      items, 1 depression-related item, 2 self-esteem items, and 4 alcohol- or tobacco
      related variables). The model yielded a c-statistic of 0.77 and had good
      calibration. CONCLUSIONS: This short prognostic tool, which can be incorporated
      into busy clinical practice, was used to accurately identify adolescents at risk
      for cigarette smoking initiation.

PMID- 30275238
TI  - Screening Tools for Who Will Start Smoking and the Future of Clinical Prediction.

PMID- 30275239
TI  - Correction: Quantitative proteomics of strong and weak biofilm formers of
      Enterococcus faecalis reveals novel regulators of biofilm formation.

PMID- 30275240
TI  - Revisiting the role of metabolism during development.
AB  - An emerging view emphasizes that metabolism is highly regulated in both time and
      space. In addition, it is increasingly being recognized that metabolic pathways
      are tightly connected to specific biological processes such as cell signaling,
      proliferation and differentiation. As we obtain a better view of this
      spatiotemporal regulation of metabolism, and of the molecular mechanisms that
      connect metabolism and signaling, we can now move from largely correlative to
      more functional studies. It is, therefore, a particularly promising time to
      revisit how metabolism can affect multiple aspects of animal development. In this
      Review, we discuss how metabolism is mechanistically linked to cellular and
      developmental programs through both its bioenergetic and metabolic signaling
      functions. We highlight how metabolism is regulated across various spatial and
      temporal scales, and discuss how this regulation can influence cellular processes
      such as cell signaling, gene expression, and epigenetic and post-translational
      modifications during embryonic development.

PMID- 30275241
TI  - RON Receptor Tyrosine Kinase as a Therapeutic Target for Eradication of Triple
      Negative Breast Cancer: Efficacy of Anti-RON ADC Zt/g4-MMAE.
AB  - Triple-negative breast cancer (TNBC) is a highly diverse group of malignant
      neoplasia with poor outcome. Currently, the lack of effective therapy has
      fostered a major effort to discover new targets to treat this malignant cancer.
      Here we identified the RON receptor tyrosine kinase as a therapeutic target for
      potential TNBC treatment. We analyzed RON expression in 168 primary TNBC samples
      via tissue microarray using anti-RON IHC staining and demonstrated that RON was
      widely expressed in 76.8% TNBC samples with overexpression in 76 cases (45.2%).
      These results provide the molecular basis to target RON for TNBC therapy. To this
      end, anti-RON monoclonal antibody Zt/g4-drug monomethyl auristatin E conjugate
      (Zt/g4-MMAE) was developed with a drug to antibody ratio of 3.29 and tested in a
      panel of TNBC cell lines with different phenotypes. In vitro, Zt/g4-MMAE rapidly
      induced RON internalization, resulted in cell-cycle arrest followed by massive
      cell death. The calculated IC50 values ranged from 0.06 to 3.46 MUg/mL dependent
      on individual TNBC cell lines tested. Zt/g4-MMAE also effectively killed TNBC
      stem-like cells with RON+/CD44+/CD24- phenotypes and RON-negative TNBC cells
      through the bystander effect. In vivo, Zt/g4-MMAE at 10 mg/kg in a Q12 * 2
      regimen completely eradicated TNBC xenografts without the regrowth of xenograft
      tumors. In conclusion, increased RON expression is a pathogenic feature in
      primary TNBC samples. Zt/g4-MMAE is highly effective in eradicating TNBC
      xenografts in preclinical models. These findings lay the foundation for using
      anti-RON Zt/g4-MMAE in clinical trials as a novel strategy for TNBC treatment.

PMID- 30275244
TI  - An Introduction to the Duchenne Muscular Dystrophy Care Considerations.

PMID- 30275242
TI  - Tumor Sidedness and Enriched Gene Groups for Efficacy of First-line Cetuximab
      Treatment in Metastatic Colorectal Cancer.
AB  - Molecular differences in tumor locations may contribute to the sidedness-specific
      response to cetuximab in metastatic colorectal cancer (mCRC). We investigated
      genes associated with the response to cetuximab treatment depending on tumor
      sidedness. Our study included 77 patients with mCRC (13/63, right/left) with KRAS
      exon 2 wild-type tumors from phase II trials of first-line therapy with
      cetuximab. Expression levels of 2,551 genes were measured in tissue samples by
      HTG EdgeSeq Oncology Biomarker Panel. Univariate Cox regression analysis using
      log2 values of counts per million (CPM) was conducted in each sidedness to assess
      associations with clinical outcomes, and to define the optimal cut-off point for
      clinically significant genes. In addition, a gene set enrichment analysis (GSEA)
      was performed to identify significant gene pathways in each sidedness. Sixty-nine
      patients were assessable for gene expression data. Overexpression of BECN1
      [log2(CPM) >= 6.8] was associated with favorable survival, regardless of tumor
      sidedness. High expression of NOTCH1 [log2(CPM) >= 7.5] predicted significantly
      longer progression-free survival (PFS; median 14.7 vs. 11.1 months, HR 0.43, P =
      0.01) and overall survival (OS; median 42.8 vs. 26.5 months, HR 0.35, P = 0.01)
      in left side but not in right side. The GSEA showed that regulation of DNA
      replication gene set correlated with favorable survival in the left, whereas the
      subcellular component and leukocyte migration gene sets were associated with good
      survival in the right. In conclusion, genes contributing to the efficacy of
      cetuximab treatment may differ according to the sidedness in mCRC. NOTCH1 may
      potentially discriminate favorable responders to cetuximab in patients with left
      sided tumors.

PMID- 30275245
TI  - Neurology Care, Diagnostics, and Emerging Therapies of the Patient With Duchenne
      Muscular Dystrophy.
AB  - Duchenne muscular dystrophy is the most common form of childhood muscular
      dystrophy. A mutation in the DMD gene disrupts dystrophin (protein) production,
      causing damage to muscle integrity, weakness, loss of ambulation, and
      cardiopulmonary compromise by the second decade of life. Life expectancy has
      improved from mid-teenage years to mid-20s with the use of glucocorticoids and
      beyond the third decade with ventilator support and multidisciplinary care.
      However, Duchenne muscular dystrophy is associated with comorbidities and is a
      fatal disease. Glucocorticoids prolong ambulation, but their side effects are
      significant. Emerging investigational therapies have surfaced over the past
      decade and have rapidly been tested in clinical trials. Gene-specific strategies
      include nonsense readthrough, exon skipping, gene editing, utrophin modulation,
      and gene replacement. Other mechanisms include muscle regeneration, antioxidants,
      and antifibrosis and anti-inflammatory pathways. With potential therapies
      emerging, early diagnosis is needed to initiate treatment early enough to
      minimize morbidity and mortality. Newborn screening can be used to significantly
      improve early diagnosis, especially for gene-specific therapeutics.

PMID- 30275246
TI  - Rehabilitation Management of the Patient With Duchenne Muscular Dystrophy.
AB  - Steadily improving management of Duchenne muscular dystrophy (DMD) continues to
      lead to improved physical and functional status, allowing increasingly successful
      transitions to independence and self-actualization in adulthood. Rehabilitation
      principles remain key to overall management for individuals with DMD with
      increasing options for ever more successful management, reflecting a changing
      natural history based on the use of glucocorticoids, more consistent
      comprehensive care, and the emergence of disease-modifying treatments. Advances
      and expansion in assessment, cardiorespiratory management, preventive management
      of contracture and deformity, assistive technology, "smart" technology, and
      robotics with increased emphasis on function, participation, self-advocacy, and
      independence in decision-making should allow individuals with DMD to experience
      childhood and transition to adulthood with support that allows for increasing
      success in the achievement of individual goals and fulfillment across the life
      span.

PMID- 30275247
TI  - Bone Health and Osteoporosis Management of the Patient With Duchenne Muscular
      Dystrophy.
AB  - Duchenne muscular dystrophy is associated with an increased risk of bone
      fragility due to the adverse effects of prolonged glucocorticoid therapy and
      progressive muscle weakness on bone strength. Osteoporosis manifests clinically
      as low-trauma long-bone and vertebral fractures (VFs), with VFs frequent,
      particularly in those treated with glucocorticoid therapy. It is increasingly
      recognized that bone pain, medical complications of osteoporosis (such as fat
      embolism syndrome), and the potential for permanent, fracture-induced loss of
      ambulation can be mitigated with timely bone health surveillance and management.
      This includes periodic spine radiographs for VF detection because VFs can be
      asymptomatic in their early phases and thereby go undetected in the absence of
      monitoring. With this article, we provide a comprehensive review of the following
      4 phases of bone health management: (1) bone health monitoring, which is used to
      identify early signs of compromised bone health; (2) osteoporosis stabilization,
      which is aimed to mitigate back pain and interrupt the fracture-refracture cycle
      through bone-targeted therapy; (3) bone health maintenance, which has the goal to
      preserve the clinical gains realized during the stabilization phase through
      ongoing bone-targeted therapy; and (4) osteoporosis therapy discontinuation,
      which places those who are eligible for discontinuation of osteoporosis treatment
      back on a health monitoring program. In the course of reviewing these 4 phases of
      management, we will discuss the criteria for diagnosing osteoporosis, along with
      detailed recommendations for osteoporosis intervention including specific drugs,
      dose, length of therapy, contraindications, and monitoring of treatment efficacy
      and safety.

PMID- 30275248
TI  - Obesity and Endocrine Management of the Patient With Duchenne Muscular Dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is associated with an increased risk of
      endocrine complications due to the effects of prolonged glucocorticoid therapy as
      well as progressive muscle weakness. Categories of complications include obesity
      and its comorbidities, short stature, pubertal delay, and adrenal insufficiency.
      Obesity prevention is important for long-term management of patients with DMD.
      Preventing glucocorticoid-induced weight gain fosters patient mobility, ease of
      transfer, and reduces sleep-disordered breathing. Metabolic complications from
      obesity (glucose intolerance, dyslipidemia) also can be avoided. Short stature
      and pubertal delay may negatively affect self-esteem and peer relationships, and
      careful monitoring of growth and pubertal development can allow anticipatory
      counseling. Adrenal insufficiency, a potentially life-threatening complication
      associated with prolonged glucocorticoid use, must be recognized so as to allow
      prompt treatment. In this article, we provide a summary of current guidance to
      ensure comprehensive endocrine management is followed in patients with DMD.

PMID- 30275249
TI  - Nutritional and Gastrointestinal Management of the Patient With Duchenne Muscular
      Dystrophy.
AB  - Advances in treatment and multidisciplinary management have resulted in improved
      survival of individuals with Duchenne muscular dystrophy (DMD). Updated DMD
      treatment recommendations as found in the 2018 DMD Care Considerations are aimed
      to assist multidisciplinary care teams in providing standardized care to their
      patients, including attention to nutritional and gastrointestinal health.
      Challenges remain for care teams in accurately estimating height and nutritional
      status for individuals with DMD. It can be difficult for patients to maintain a
      healthy weight. Risk factors for obesity include glucocorticoid therapy and loss
      of ambulation. In contrast, in the later stages of the disease, swallowing
      dysfunction can lead to poor nutrition and consideration for gastrostomy tube
      placement. Constipation is highly prevalent, underrecognized, and undertreated in
      DMD. With this article, we address the assessment and management of
      gastrointestinal and nutritional issues, as well as clinical controversies.

PMID- 30275250
TI  - Respiratory Management of the Patient With Duchenne Muscular Dystrophy.
AB  - In 2010, Care Considerations for Duchenne Muscular Dystrophy, sponsored by the
      Centers for Disease Control and Prevention, was published in Lancet Neurology,
      and in 2018, these guidelines were updated. Since the publication of the first
      set of guidelines, survival of individuals with Duchenne muscular dystrophy has
      increased. With contemporary medical management, survival often extends into the
      fourth decade of life and beyond. Effective transition of respiratory care from
      pediatric to adult medicine is vital to optimize patient safety, prognosis, and
      quality of life. With genetic and other emerging drug therapies in development,
      standardization of care is necessary to accurately assess treatment effects in
      clinical trials. This revision of respiratory recommendations preserves a
      fundamental strength of the original guidelines: namely, reliance on a limited
      number of respiratory tests to guide patient assessment and management. A
      progressive therapeutic strategy is presented that includes lung volume
      recruitment, assisted coughing, and assisted ventilation (initially nocturnally,
      with the subsequent addition of daytime ventilation for progressive respiratory
      failure). This revision also stresses the need for serial monitoring of
      respiratory muscle strength to characterize an individual's respiratory phenotype
      of severity as well as provide baseline assessments for clinical trials. Clinical
      controversies and emerging areas are included.

PMID- 30275251
TI  - Cardiac Management of the Patient With Duchenne Muscular Dystrophy.
AB  - Duchenne muscular dystrophy (DMD) results in a progressive cardiomyopathy that
      produces significant morbidity and mortality. To improve the quality of life in
      patients with DMD, cardiac care is focused on surveillance and management, with
      the goal of slowing the onset and progression of heart failure complications. The
      current article is intended to be an expanded review on the cardiac management
      data used to inform the 2018 DMD Care Considerations recommendations as well as
      be a discussion on clinical controversies and future management directions. The
      new cardiac guidance includes changes regarding noninvasive imaging surveillance
      of cardiac function and pharmacologic therapy. Many emerging therapies lack
      sufficient evidence-based data to be recommended in the 2018 DMD Care
      Considerations. These are discussed in the present article as clinical
      controversies and future directions. Important emerging therapies include new
      heart failure medications, mechanical circulatory support with ventricular assist
      devices, heart transplantation, and internal cardiac defibrillators. Future
      research studies should be focused on the risks and benefits of these advanced
      therapies in patients with DMD. We conclude this review with a brief discussion
      on the relationship between the heart and the recently developed medications that
      are used to directly target the absence of dystrophin in DMD.

PMID- 30275252
TI  - Orthopedic and Surgical Management of the Patient With Duchenne Muscular
      Dystrophy.
AB  - Orthopedic care is an important aspect of the overall management of patients with
      Duchenne muscular dystrophy (DMD). In addition to progressive muscle weakness and
      loss of function, patients may develop joint contractures, scoliosis, and
      osteoporosis, causing fractures; all of these necessitate intervention by a
      multidisciplinary team including an orthopedic surgeon as well as rehabilitation
      specialists such as physio- and occupational therapists. The causes of these
      musculoskeletal complications are multifactorial and are related to primary
      effects on the muscles from the disease itself, secondary effects from weak
      muscles, and the related side effects of treatments, such as glucocorticoid use
      that affect bone strength. The musculoskeletal manifestations of DMD change over
      time as the disease progresses, and therefore, musculoskeletal management needs
      change throughout the life span of an individual with DMD. In this review, we
      target pediatricians, neurologists, orthopedic surgeons, rehabilitation
      physicians, anesthesiologists, and other individuals involved in the management
      of patients with DMD by providing specific recommendations to guide clinical
      practice related to orthopedic issues and surgical management in this setting.

PMID- 30275253
TI  - Primary Care and Emergency Department Management of the Patient With Duchenne
      Muscular Dystrophy.
AB  - Primary care providers (PCPs) are usually the first point of contact with the
      health care system for patients with Duchenne muscular dystrophy (DMD), and
      patients often present to emergency departments in which providers have little
      experience in dealing with this condition. With this article, we give primary
      care and emergency medicine providers a background in the common issues that
      affect people with DMD. By acquiring some specialized knowledge about the
      multisystem medical complications of DMD and by applying general principles of
      primary care, such as timely immunization, anticipatory safety counseling,
      behavioral screening, and routine nutritional and developmental assessments, the
      PCP can be a valued and effective medical provider to patients with DMD. The PCP
      can provide access to and effective coordination among the patient's specialty
      caregivers. Moreover, the PCP can become a trusted advisor to the patient and his
      family about important medical decisions, as well as issues in the psychosocial,
      behavioral, and educational domains. This article also contains a "pocket guide"
      used to assess and manage common urgent medical problems that cause patients with
      DMD to seek care in the emergency department. With the background information
      discussed in this article, both PCPs and emergency medicine physicians can
      skillfully care for patients with DMD in their respective settings, optimizing
      patient outcomes.

PMID- 30275254
TI  - Psychosocial Management of the Patient With Duchenne Muscular Dystrophy.
AB  - In this article, we outline a comprehensive plan for the psychosocial management
      of patients with Duchenne muscular dystrophy (DMD) across the life span. In 2010,
      the Centers for Disease Control and Prevention sponsored the development of
      multidisciplinary management guidance for DMD, and in 2018, that guidance was
      updated. In the intervening years, a new emphasis was placed on studying and
      addressing the psychosocial issues that affect patients with DMD, driven in part
      by improved patient survival. Once viewed as ancillary to managing the
      significant medical needs of patients with DMD, it is now standard practice to
      integrate psychosocial management into the multidisciplinary management of the
      disease. It is also increasingly recognized that neurodevelopmental disorders in
      DMD occur at a higher rate than what was previously understood and that these
      disorders warrant early and intensive intervention. In this article, we expand on
      the content found in the 2018 DMD Care Considerations.

PMID- 30275255
TI  - A Transition Toolkit for Duchenne Muscular Dystrophy.
AB  - The care of individuals with Duchenne muscular dystrophy (DMD) now extends into
      adulthood. Childhood to adulthood transition planning is an important aspect of
      care, affecting health outcomes as well as other important aspects of adult life.
      In this article, we address transition planning as it relates to DMD health care,
      education, steps toward vocations, personal care, accessing the home and
      community, and the importance of relationships with others. Because of the
      complex, disabling, and progressive nature of DMD, coordinated, well-timed
      planning is critical to ensure that all components of transition are
      accomplished. In this article, we introduce the DMD Transition Toolkit. The
      toolkit is designed to help assess readiness for transition, track progress
      toward transition goals, and provide a template for documenting key elements of
      medical care, medical equipment, and services. The transition readiness
      assessment for young adults with DMD is used to gauge readiness for adult health
      care and living practices. Consistent with the 2018 DMD Care Considerations, the
      transition checklist for young adults with DMD is a comprehensive list to be
      considered, discussed, and planned for during transition. The medical summary for
      young adults with DMD can be used by a provider or individuals with DMD to
      communicate details of their health plan, provider contacts, and medical
      equipment needs. It can be used in transition handoffs, when adding new
      providers, or when informing new nursing agencies or personal care attendants. It
      could also be useful in urgent care settings by providing baseline information
      about the individual with DMD.

PMID- 30275256
TI  - Evaluating Implementation of the Updated Care Considerations for Duchenne
      Muscular Dystrophy.
AB  - Care Considerations for Duchenne Muscular Dystrophy were published in 2010.
      However, little is known about the extent to which these considerations were
      implemented after publication. With this article, we provide direction on
      evaluating the uptake of the 2018 Duchenne Muscular Dystrophy Care
      Considerations. We identify key elements of care and present suggestions for
      their use in evaluation and research.

PMID- 30275257
TI  - Hydroxychloroquine Levels throughout Pregnancies Complicated by Rheumatic
      Disease: Implications for Maternal and Neonatal Outcomes.
AB  - OBJECTIVE: Pregnancies in women with active rheumatic disease often result in
      poor neonatal outcomes. Hydroxychloroquine (HCQ) reduces disease activity and
      flares; however, pregnancy causes significant physiologic changes that may alter
      HCQ levels and lead to therapeutic failure. Therefore, our objective was to
      evaluate HCQ concentrations during pregnancy and relate levels to outcomes.
      METHODS: We performed an observational study of pregnant patients with rheumatic
      disease who were taking HCQ from a single center during 2013-2016. Serum samples
      were analyzed using high-performance liquid chromatography/mass spectrometry.
      Primary HCQ exposure was categorized as nontherapeutic (<= 100 ng/ml) or
      therapeutic (> 100 ng/ml). Categorical outcomes were analyzed using Fisher's
      exact test and continuous outcomes using linear regression models, Wilcoxon
      signed-rank test, Kruskal-Wallis test, t test, and ANOVA. RESULTS: We analyzed
      145 samples from 50 patients with rheumatic disease, 56% of whom had systemic
      lupus erythematosus (SLE). HCQ concentration varied widely among individuals at
      each trimester. Mean physician's global assessment scores in patients with SLE
      were significantly higher in those with average drug levels <= 100 ng/ml compared
      to > 100 ng/ml (0.93 vs 0.32, p = 0.01). Of patients with SLE, 83% with average
      drug levels <= 100 ng/ml delivered prematurely (n = 6), compared to only 21% with
      average levels > 100 ng/ml (n = 19; p = 0.01). HCQ levels were not associated
      with prematurity or disease activity in non-SLE patients. CONCLUSION: With both
      high and low HCQ levels associated with preterm birth and disease activity in
      SLE, further study is necessary to understand HCQ disposition throughout
      pregnancy and to clarify the relationship between drug levels and outcomes.

PMID- 30275258
TI  - Performance of the Expanded Cardiovascular Risk Prediction Score for Rheumatoid
      Arthritis Is Not Superior to the ACC/AHA Risk Calculator.
AB  - OBJECTIVE: Cardiovascular (CV) risk estimation calculators for the general
      population do not perform well in patients with rheumatoid arthritis (RA). An RA
      specific risk calculator has been developed, but did not perform better than a
      risk calculator for the general population when validated in a heterogeneous
      multinational cohort. METHODS: In a cohort of patients with new-onset RA from
      northern Sweden (n = 665), the risk of CV disease was estimated by the Expanded
      Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA) and the
      American College of Cardiology/American Heart Association algorithm (ACC/AHA).
      The ACC/AHA estimation was analyzed, both as crude data and when adjusted
      according to the recommendations by the European League Against Rheumatism
      (ACC/AHA * 1.5). ERS-RA was calculated using 2 variants: 1 from patient and
      physician reports of hypertension (HTN) and hyperlipidemia [ERS-RA (reported)]
      and 1 from assessments of blood pressure (BP) and blood lipids [ERS-RA
      (measured)]. The estimations were compared with observed CV events. RESULTS: All
      variants of risk calculators underestimated the CV risk. Discrimination was good
      for all risk calculators studied. Performance of all risk calculators was poorer
      in patients with a high grade of inflammation, whereas ACC/AHA * 1.5 performed
      best in the high-inflammatory patients. In those patients with an estimated risk
      of 5-15%, no risk calculator performed well. CONCLUSION: ERS-RA underestimated
      the risk of a CV event in our cohort of patients, especially when risk
      estimations were based on patient or physician reports of HTN and hyperlipidemia
      instead of assessment of BP and blood lipids. The performance of ERS-RA was no
      better than that of ACC/AHA * 1.5, and neither performed well in high
      inflammatory patients.

PMID- 30275259
TI  - Toward New Classification Criteria for Juvenile Idiopathic Arthritis: First
      Steps, Pediatric Rheumatology International Trials Organization International
      Consensus.
AB  - OBJECTIVE: To revise the current juvenile idiopathic arthritis (JIA)
      International League of Associations for Rheumatology (ILAR) classification
      criteria with an evidence-based approach, using clinical and routine laboratory
      measures available worldwide, to identify homogeneous clinical groups and to
      distinguish those forms of chronic arthritis typically seen only in children from
      the childhood counterpart of adult diseases. METHODS: The overall project
      consists of 4 steps. This work represents Step 1, a Delphi Web-based consensus
      and Step 2, an international nominal group technique (NGT) consensus conference
      for the new provisional Pediatric Rheumatology International Trials Organization
      JIA classification criteria. A future large data collection of at least 1000 new
      onset JIA patients (Step 3) followed by analysis and NGT consensus (Step 4) will
      provide data for the evidence-based validation of the JIA classification
      criteria. RESULTS: In Step 1, three Delphi rounds of interactions were
      implemented to revise the 7 ILAR JIA categories. In Step 2, forty-seven questions
      with electronic voting were implemented to derive the new proposed criteria. Four
      disorders were proposed: (a) systemic JIA; (b) rheumatoid factor-positive JIA;
      (c) enthesitis/spondylitis-related JIA; and (d) early-onset antinuclear antibody
      positive JIA. The other forms were gathered under the term "others." These will
      be analyzed during the prospective data collection using a list of descriptors to
      see whether the clustering of some of them could identify homogeneous entities.
      CONCLUSION: An international consensus was reached to identify different proposed
      homogeneous chronic disorders that fall under the historical term JIA. These
      preliminary criteria will be formally validated with a dedicated project.

PMID- 30275261
TI  - Relationship Between Insulin Sensitivity and beta-Cell Secretion in Nondiabetic
      Subjects with Rheumatoid Arthritis.
AB  - OBJECTIVE: In nondiabetic healthy individuals, insulin secretion and sensitivity
      are linked by a negative feedback loop characterized by a hyperbolic function. We
      aimed to study the association of traditional insulin resistance (IR) factors
      with insulin secretion and sensitivity, and to determine whether the hyperbolic
      equilibrium of this relation is preserved in patients with rheumatoid arthritis
      (RA). METHODS: This was a cross-sectional study encompassing 361 nondiabetic
      individuals: 151 with RA and 210 controls. Insulin, C-peptide, and IR indices by
      homeostatic model (HOMA2) were assessed. A multivariable analysis was performed
      to evaluate the differences in the correlation of traditional IR-related factors
      with glucose homeostasis molecules, as well as IR indices between patients and
      controls. Nonlinear regression analysis was used to assess the hyperbolic
      relation of insulin sensitivity and secretion. RESULTS: HOMA2-IR indices were
      higher in patients with RA than controls. Hepatic insulin extraction, as assessed
      by the insulin:C-peptide molar ratio, was lower in patients with RA after
      multivariable analysis (0.08 +/- 0.02 vs 0.14 +/- 0.07, p < 0.001). Traditional
      IR-related factors showed significantly lower adjusted correlation coefficients
      with IR indices in patients with RA. The association between insulin sensitivity
      and secretion showed a different hyperbolic relation in patients with RA: the
      variability explained by the curve was lower in RA (nonlinear r2 = 0.845 vs r2 =
      0.928, p = 0.001) and beta coefficients (-0.74, 95% CI -0.77 to -0.70 vs -1.09,
      95% CI -1.17 to -1.02, ng/ml, p < 0.001) were different in RA. CONCLUSION: The
      traditional factors associated with IR in healthy individuals are less related to
      IR in patients with RA. Insulin sensitivity and secretion yield a different
      hyperbolic equilibrium in RA.

PMID- 30275262
TI  - Biologic and Glucocorticoid Use after Methotrexate Initiation in Patients with
      Rheumatoid Arthritis.
AB  - OBJECTIVE: Biologic therapies can improve disease control for patients with
      rheumatoid arthritis (RA) but may be both overused and underused. We aimed to
      identify predictors of greater use of biologic therapies and to identify factors
      associated with persistent glucocorticoid use. METHODS: Using national US
      Veteran's Affairs databases 2005-2016, we identified patients with RA receiving a
      first-ever prescription of methotrexate (MTX), requiring >= 6 months of baseline
      data. We evaluated predictors of biologic therapy initiation within 2 years of
      starting MTX and factors associated with baseline and persistent glucocorticoid
      use at 6-12 months using multivariable models. RESULTS: Among 17,415 patients
      starting MTX, 3263 patients received biologic therapy within 2 years (20.6% 2-yr
      incidence). In adjusted analyses, biologic use was substantially lower in older
      patients [e.g., aHR 0.20 (95% CI 0.16, 0.26) for patients >= 80 vs < 50] and
      patients with more comorbidities [aHR 0.79 (95% CI 0.72, 0.87) for Charlson score
      >= 3 vs < 3]. Patients with heart failure [aHR 0.68 (95% CI 0.54, 0.84)], cancer
      [aHR 0.78 (95% CI 0.66, 0.92)], or who were nonwhite [aHR 0.79 (95% CI 0.72,
      0.87)] were also less likely to receive a biologic. In contrast, baseline and
      persistent glucocorticoid use was similar across age groups and more common in
      patients with greater comorbidity. CONCLUSION: Biologic therapy is initiated less
      frequently in patients with RA who are older, have more comorbidities, and who
      are nonwhite. While biologics may be avoided in older and sicker patients because
      of safety concerns, glucocorticoid use is similar regardless of age and is more
      frequent in patients with comorbidities, with implications for patient outcomes.

PMID- 30275260
TI  - Risk Factors for Mortality and Cardiopulmonary Hospitalization in Systemic
      Sclerosis Patients At Risk for Pulmonary Hypertension, in the PHAROS Registry.
AB  - OBJECTIVE: We sought to identify predictors of mortality and cardiopulmonary
      hospitalizations in patients at risk for pulmonary hypertension (PH) and enrolled
      in PHAROS, a prospective cohort study to investigate the natural history of PH in
      systemic sclerosis (SSc). METHODS: The at-risk population for PH was defined by
      the following entry criteria: echocardiogram systolic pulmonary arterial pressure
      > 40 mmHg, or DLCO < 55% predicted or ratio of % forced vital capacity/%DLCO >
      1.6, measured by pulmonary function testing. Baseline clinical measures were
      evaluated as predictors of hospitalization and death between 2005 and 2014. Cox
      proportional hazards models were censored at date of PH onset or latest study
      visit and adjusted for age, sex, race, and disease duration. RESULTS: Of the 236
      at-risk subjects who were followed for a median of 4 years (range 0.4-8.5 yrs),
      35 developed PH after entering PHAROS (reclassified as PH group). In the at-risk
      group, higher mortality was strongly associated with male sex, low %DLCO,
      exercise oxygen desaturation, anemia, abnormal dyspnea scores, and baseline
      pericardial effusion. Risks for cardiopulmonary hospitalization were associated
      with increased dyspnea and pericardial effusions, although PH patients with DLCO
      < 50% had the highest risk of cardiopulmonary hospitalizations. CONCLUSION: Risk
      factors for poor outcome in patients with SSc who are at risk for PH were similar
      to others with SSc-PH and SSc-pulmonary arterial hypertension, including male
      sex, DLCO < 50%, exercise oxygen desaturation, and pericardial effusions. This
      group should undergo right heart catheterization and receive appropriate
      intervention if PH is confirmed.

PMID- 30275263
TI  - Quadriceps Weakness and the Risk of Knee Cartilage Loss Seen on Magnetic
      Resonance Imaging in a Population-based Cohort with Knee Pain.
AB  - OBJECTIVE: To determine whether baseline quadriceps weakness predicts cartilage
      loss assessed on magnetic resonance imaging (MRI). METHODS: Subjects aged 40-79
      with knee pain (n = 163) were recruited from a random population sample and
      examined for quadriceps weakness with manual isometric strength testing, using a
      3-point scoring system (0 = poor resistance, 1 = moderate resistance, 2 = full
      resistance), which was dichotomized as normal (grade 2) versus weak (grade 0/1).
      MRI of the more symptomatic knee was obtained at baseline and at mean of 3.3
      years. Cartilage was graded 0-4 on MRI. Exponential regression analysis was used
      to evaluate whether quadriceps weakness was associated with whole knee cartilage
      loss, and in secondary analyses with compartment-specific cartilage loss,
      adjusted for age, sex, body mass index, Western Ontario and McMaster Universities
      Osteoarthritis Arthritis Index pain score, and baseline MRI cartilage score.
      RESULTS: Of 163 subjects, 54% were female, with a mean age of 57.7 years.
      Quadriceps weakness was seen in 11.9% of the subjects. Weakness was a predictor
      of whole knee cartilage loss (HR 3.48, 95% CI 1.30-9.35). Quadriceps weakness was
      associated with cartilage loss in the medial tibiofemoral (TF) compartment (HR
      4.60, 95% CI 1.25-17.02), while no significant association was found with lateral
      TF (HR 1.53, 95% CI 0.24-9.78) or patellofemoral compartment (HR 2.76, 95% CI
      0.46-16.44). CONCLUSION: In this symptomatic, population-based cohort, quadriceps
      weakness predicted whole knee and medial TF cartilage loss after 3 years. To our
      knowledge, this is the first study to show that a simple clinical examination of
      quadriceps strength can predict the risk of knee cartilage loss.

PMID- 30275264
TI  - Longterm Data on Sirolimus Treatment in Patients with Lupus Nephritis.
AB  - OBJECTIVE: To expand the limited longterm data on sirolimus treatment in patients
      with lupus nephritis (LN). Our pilot short-term data suggested efficacy of
      sirolimus treatment in these patients. METHODS: We retrospectively reviewed 16
      class III/IV/V patients with LN who have received prednisolone (PSL) and
      sirolimus either as initial or maintenance treatment. RESULTS: Sixteen patients
      received sirolimus treatment (9 because of intolerance to standard
      immunosuppressants and 7 because of a history of malignancy) for 45.3 +/- 36.5
      months. In 5 patients, sirolimus and PSL were given as induction for active
      nephritis, and they showed improvements in proteinuria (2.8 +/- 1.9 g/day at
      baseline, 0.1 +/- 0.1 g/day after 36 mos, p = 0.011), anti-dsDNA (107.7 +/- 91.9
      IU/ml and 37.0 +/- 55.4 IU/ml, respectively, p = 0.178), and C3 (54.8 +/- 26.1
      mg/dl and 86.3 +/- 18.6 mg/dl, respectively, p = 0.081). Eleven patients received
      sirolimus and low-dose PSL as longterm maintenance, and they showed continued
      improvement in C3 (90.4 +/- 18.1 mg/dl and 117.7 +/- 25.1 mg/dl at commencement
      and after 36 mos, respectively, p = 0.025), stable renal function (estimated
      glomerular filtration rate 58.6 +/- 25.8 ml/min and 63.0 +/- 29.6 ml/min,
      respectively, p = 0.239), and proteinuria (0.8 +/- 0.7 g/day and 0.7 +/- 0.7
      g/day respectively, p = 0.252). Renal flare occurred in 1 patient, and another
      patient who had stage 4 chronic kidney disease when sirolimus was started
      developed endstage renal failure after 27 months. Sirolimus was discontinued in 5
      patients, in 4 cases related to drug side effects. Deterioration of dyslipidemia
      occurred in 4 patients, but was adequately controlled with statin therapy.
      CONCLUSION: The preliminary evidence suggests that sirolimus may serve as an
      alternative treatment for patients with LN who do not tolerate standard treatment
      or who had a history of malignancy, and it has an acceptable longterm safety
      profile.

PMID- 30275265
TI  - Performance of Forced Vital Capacity and Lung Diffusion Cutpoints for Associated
      Radiographic Interstitial Lung Disease in Systemic Sclerosis.
AB  - OBJECTIVE: Forced vital capacity (FVC) and DLCO are used for screening of
      systemic sclerosis-associated interstitial lung disease (SSc-ILD). The study
      purpose was to determine the sensitivity, specificity, and negative predictive
      value (NPV) (proportion of true negative screening tests) of FVC and DLCO
      thresholds for SSc-ILD on chest high-resolution computed tomography (HRCT) scans.
      METHODS: Patients fulfilling American College of Rheumatology 2013 SSc criteria
      with a chest HRCT scan and pulmonary function tests (PFT) were studied. A
      thoracic radiologist quantified radiographic ILD. Optimal FVC and DLCO %
      predicted thresholds for ILD were identified using receiver-operating
      characteristic curves. The FVC and DLCO combinations with greatest sensitivity
      and specificity were also determined. Subanalysis was performed in patients with
      positive Scl-70 autoantibodies. RESULTS: The study included 265 patients. Of 188
      (71%) with radiographic ILD, 59 (31%) had "normal" FVC (>= 80% predicted), and 65
      out of 151 (43%) had "normal" DLCO (>= 60% predicted). FVC < 80% (sensitivity
      0.69, specificity 0.73), and DLCO < 62% (sensitivity 0.60, specificity 0.70) were
      optimal thresholds for radiographic SSc-ILD. All FVC and DLCO threshold
      combinations evaluated had NPV < 0.70. The NPV for radiographic ILD for FVC < 80%
      was lower in patients with positive Scl-70 autoantibody (NPV = 0.05) compared to
      negative Scl-70 autoantibody (NPV = 0.57). CONCLUSION: Radiographic ILD is
      prevalent in SSc despite "normal" PFT. No % predicted FVC or DLCO threshold
      combinations yielded high NPV for SSc-ILD screening. "Normal" FVC and DLCO in
      patients with SSc, especially those with positive Scl-70 autoantibodies, should
      not obviate consideration of HRCT for ILD evaluation.

PMID- 30275267
TI  - Alpha-ketoglutarate: a "magic" metabolite in early germ cell development.

PMID- 30275268
TI  - Epigenetically jump starting de novo shoot regeneration.

PMID- 30275266
TI  - Esrrb extinction triggers dismantling of naive pluripotency and marks commitment
      to differentiation.
AB  - Self-renewal of embryonic stem cells (ESCs) cultured in LIF/fetal calf serum
      (FCS) is incomplete with some cells initiating differentiation. While this is
      reflected in heterogeneous expression of naive pluripotency transcription factors
      (TFs), the link between TF heterogeneity and differentiation is not fully
      understood. Here, we purify ESCs with distinct TF expression levels from LIF/FCS
      cultures to uncover early events during commitment from naive pluripotency. ESCs
      carrying fluorescent Nanog and Esrrb reporters show Esrrb downregulation only in
      Nanoglow cells. Independent Esrrb reporter lines demonstrate that Esrrbnegative
      ESCs cannot effectively self-renew. Upon Esrrb loss, pre-implantation
      pluripotency gene expression collapses. ChIP-Seq identifies different regulatory
      element classes that bind both OCT4 and NANOG in Esrrbpositive cells. Class I
      elements lose NANOG and OCT4 binding in Esrrbnegative ESCs and associate with
      genes expressed preferentially in naive ESCs. In contrast, Class II elements
      retain OCT4 but not NANOG binding in ESRRB-negative cells and associate with more
      broadly expressed genes. Therefore, mechanistic differences in TF function act
      cumulatively to restrict potency during exit from naive pluripotency.

PMID- 30275271
TI  - Retraction: Apoptosis-Inducing Effect of Erlotinib Is Potentiated by 3,3'
      Diindolylmethane In Vitro and In Vivo Using an Orthotopic Model of Pancreatic
      Cancer.

PMID- 30275269
TI  - Nonsense-mediated mRNA decay involves two distinct Upf1-bound complexes.
AB  - Nonsense-mediated mRNA decay (NMD) is a translation-dependent RNA degradation
      pathway involved in many cellular pathways and crucial for telomere maintenance
      and embryo development. Core NMD factors Upf1, Upf2 and Upf3 are conserved from
      yeast to mammals, but a universal NMD model is lacking. We used affinity
      purification coupled with mass spectrometry and an improved data analysis
      protocol to characterize the composition and dynamics of yeast NMD complexes in
      yeast (112 experiments). Unexpectedly, we identified two distinct complexes
      associated with Upf1: Upf1-23 (Upf1, Upf2, Upf3) and Upf1-decapping Upf1
      decapping contained the mRNA decapping enzyme, together with Nmd4 and Ebs1, two
      proteins that globally affected NMD and were critical for RNA degradation
      mediated by the Upf1 C-terminal helicase region. The fact that Nmd4 association
      with RNA was partially dependent on Upf1-23 components and the similarity between
      Nmd4/Ebs1 and mammalian Smg5-7 proteins suggest that NMD operates through
      conserved, successive Upf1-23 and Upf1-decapping complexes. This model can be
      extended to accommodate steps that are missing in yeast, to serve for further
      mechanistic studies of NMD in eukaryotes.

PMID- 30275273
TI  - Retraction: Downregulation of Notch-1 Contributes to Cell Growth Inhibition and
      Apoptosis in Pancreatic Cancer Cells.

PMID- 30275272
TI  - Retraction: Therapeutic Intervention of Experimental Breast Cancer Bone
      Metastasis by Indole-3-carbinol in SCID-human Mouse Model.

PMID- 30275275
TI  - Technique Development for Probing RNA Structure In Vivo and Genome-Wide.
AB  - SUMMARYHow organisms perceive and respond to their surroundings is one of the
      great questions in biology. It is clear that RNA plays key roles in sensing.
      Cellular and environmental cues that RNA responds to include temperature, ions,
      metabolites, and biopolymers. Recent advances in next-generation sequencing and
      in vivo chemical probing have provided unprecedented insights into RNA folding in
      vivo and genome-wide. Patterns of chemical reactivity have implicated control of
      gene expression by RNA and aided prediction of RNA structure. Central to these
      advances has been development of molecular biological and chemical techniques.
      Key advances are improvements in the quality, cost, and throughput of library
      preparation; availability of a wider array of chemicals for probing RNA structure
      in vivo; and robustness and user friendliness of data analysis. Insights from
      probing transcriptomes and future directions are provided.

PMID- 30275274
TI  - Clinical Significance of Pancreatic Atrophy Induced by Immune-Checkpoint
      Inhibitors: A Case-Control Study.
AB  - Immune-checkpoint inhibitor (ICI)-related diarrhea is attributed to inflammatory
      colitis, with no other drug-related differential diagnosis. Here, we investigated
      the occurrence of pancreatic atrophy (PA) in ICI-treated cancer patients and its
      correlation to exocrine pancreatic insufficiency (EPI). Metastatic melanoma, non
      small cell lung carcinoma, and head and neck squamous cell carcinoma patients (n
      = 403) treated with anti-PD-1 (n = 356) or anti-CTLA-4 (n = 47) were divided into
      a case group (radiologic evidence of PA); control group matched by age, gender,
      and previous lines of treatment; and colitis group (ICI-induced colitis).
      Quantitative pancreatic volumetry was used for calculation of the decrease in
      pancreatic volume over time (atrophy rate). Thirty-one patients (7.7%) developed
      PA compared with 41 matched controls (P = 0.006). Four patients developed EPI,
      all from the anti-PD-1-treated group, which resolved with oral enzyme
      supplementation. The atrophy rate did not correlate with EPI (P = 0.87). EPI
      related diarrhea presented at a median of 9 months, whereas the diarrhea of anti
      PD-1-induced colitis patients (n = 22) was presented at a median of 2 months (P =
      0.029). ICI-induced PA is irreversible and can result in EPI. EPI should be
      suspected in cases of late-onset steroid-resistant diarrhea with features of
      steatorrhea and treated with oral enzyme supplements.

PMID- 30275276
TI  - The Story of RNA Folding, as Told in Epochs.
AB  - SUMMARYThe past decades have witnessed tremendous developments in our
      understanding of RNA biology. At the core of these advances have been studies
      aimed at discerning RNA structure and at understanding the forces that influence
      the RNA folding process. It is easy to take the present state of understanding
      for granted, but there is much to be learned by considering the path to our
      current understanding, which has been tortuous, with the birth and death of
      models, the adaptation of experimental tools originally developed for
      characterization of protein structure and catalysis, and the development of novel
      tools for probing RNA. In this review we tour the stages of RNA folding studies,
      considering them as "epochs" that can be generalized across scientific
      disciplines. These epochs span from the discovery of catalytic RNA, through
      biophysical insights into the putative primordial RNA World, to characterization
      of structured RNAs, the building and testing of models, and, finally, to the
      development of models with the potential to yield generalizable predictive and
      quantitative models for RNA conformational, thermodynamic, and kinetic behavior.
      We hope that this accounting will aid others as they navigate the many
      fascinating questions about RNA and its roles in biology, in the past, present,
      and future.

PMID- 30275277
TI  - At the Crossroads of Science and Society: Careers in Science Policy.
AB  - Science policy offers a challenging and rewarding career path for scientists
      interested in the social, ethical, and legal implications of their field. This
      topic encompasses a broad spectrum of activities all in support of advancing the
      scientific enterprise. Science policy spans various sectors, and policy careers
      are found in many different organizations, including the federal government,
      scientific societies, and professional organizations. Although their specific
      duties may vary greatly, science policy professionals generally apply their
      scientific training to ensure that the scientific enterprise advances in a
      responsible and ethical manner and to solve challenges with broad scientific and
      societal implications.

PMID- 30275278
TI  - The Manganese-Dependent Pyruvate Kinase PykM Is Required for Wild-Type Glucose
      Utilization by Brucella abortus 2308 and Its Virulence in C57BL/6 Mice.
AB  - Pyruvate kinase plays a central role in glucose catabolism in bacteria, and
      efficient utilization of this hexose has been linked to the virulence of Brucella
      strains in mice. The brucellae produce a single pyruvate kinase which is an
      ortholog of the Bradyrhizobium manganese (Mn)-dependent pyruvate kinase PykM. A
      biochemical analysis of the Brucella pyruvate kinase and phenotypic analysis of a
      Brucella abortus mutant defective in high-affinity Mn import indicate that this
      enzyme is an authentic PykM ortholog which functions as a Mn-dependent enzyme in
      vivo The loss of PykM has a negative impact on the capacity of the parental 2308
      strain to utilize glucose, fructose, and galactose but not on its ability to
      utilize ribose, xylose, arabinose, or erythritol, and a pykM mutant displays
      significant attenuation in C57BL/6 mice. Although the enzyme pyruvate phosphate
      dikinase (PpdK) can substitute for the loss of pyruvate kinase in some bacteria
      and is also an important virulence determinant in Brucella, a phenotypic analysis
      of B. abortus 2308 and isogenic pykM, ppdK, and pykM ppdK mutants indicates that
      PykM and PpdK make distinctly different contributions to carbon metabolism and
      virulence in these bacteria.IMPORTANCE Mn plays a critical role in the physiology
      and virulence of Brucella strains, and the results presented here suggest that
      one of the important roles that the high-affinity Mn importer MntH plays in the
      pathogenesis of these strains is supporting the function of the Mn-dependent
      kinase PykM. A better understanding of how the brucellae adapt their physiology
      and metabolism to sustain their intracellular persistence in host macrophages
      will provide knowledge that can be used to design improved strategies for
      preventing and treating brucellosis, a disease that has a significant impact on
      both the veterinary and public health communities worldwide.

PMID- 30275279
TI  - Co-assembly of SecYEG and SecA fully restores the properties of the native
      translocon.
AB  - In all cells a highly conserved channel transports proteins across membranes. In
      E.coli, that channel is SecYEG. Many investigations of this protein complex have
      used purified SecYEG reconstituted into proteoliposomes. How faithfully do
      activities of reconstituted systems reflect the properties of SecYEG in the
      native membrane environment? We investigated by comparing three in vitro systems:
      the native membrane environment of inner membrane vesicles and two methods of
      reconstitution. One method was the widely used reconstitution of SecYEG alone
      into lipid bilayers. The other was our method of co-assembly of SecYEG with SecA,
      the ATPase of the translocase. For nine different precursor species we assessed
      parameters that characterize translocation: maximal amplitude of competent
      precursor translocated, coupling of energy to transfer, and apparent rate
      constant. In addition we investigated translocation in the presence and absence
      of chaperone SecB. For all nine precursors, SecYEG co-assembled with SecA was as
      active as SecYEG in native membrane for each of the parameters studied. Effects
      of SecB on transport of precursors faithfully mimicked observations made in vivo
      From investigation of the nine different precursors, we conclude that the
      apparent rate constant, which reflects the step that limits the rate of
      translocation, is dependent on interactions with the translocon of portions of
      the precursors other than the leader. In addition, in some cases the rate
      limiting step is altered by the presence of SecB. Candidates for the rate
      limiting step that are consistent with our data are discussed.

PMID- 30275280
TI  - Methylation-Induced Hypermutation in Natural Populations of Bacteria.
AB  - Methylation of DNA at the C-5 position of cytosine occurs in diverse organisms.
      This modification can increase the rate of C->T transitions at the methylated
      position. In Escherichia coli and related enteric bacteria, the inner C residues
      of the sequence CCWGG (W is A or T) are methylated by the Dcm enzyme. These sites
      are hot spots of mutation during rapid growth in the laboratory but not in
      nondividing cells, in which repair by the Vsr protein is effective. It has been
      suggested that hypermutation at these sites is a laboratory artifact and does not
      occur in nature. Many other methyltransferases, with a variety of specificities,
      can be found in bacteria, usually associated with restriction enzymes and
      confined to a subset of the population. Their methylation targets are also
      possible sites of hypermutation. Here, I show using whole-genome sequence data
      for thousands of isolates that there is indeed considerable hypermutation at Dcm
      sites in natural populations: their transition rate is approximately eight times
      the average. I also demonstrate hypermutability of targets of restriction
      associated methyltransferases in several distantly related bacteria: methylation
      increases the transition rate by a factor ranging from 12 to 58. In addition, I
      demonstrate how patterns of hypermutability inferred from massive sequence data
      can be used to determine previously unknown methylation patterns and
      methyltransferase specificities.IMPORTANCE A common type of DNA modification,
      addition of a methyl group to cytosine (C) at carbon atom C-5, can greatly
      increase the rate of mutation of the C to a T. In mammals, methylation of CG
      sequences increases the rate of CG->TG mutations. It is unknown whether cytosine
      C-5 methylation increases the mutation rate in bacteria under natural conditions.
      I show that sites methylated by the Dcm enzyme exhibit an 8-fold increase in
      mutation rate in natural bacterial populations. I also show that modifications at
      other sites in various bacteria also increase the mutation rate, in some cases by
      a factor of forty or more. Finally, I demonstrate how this phenomenon can be used
      to infer sequence specificities of methylation enzymes.

PMID- 30275281
TI  - Simultaneous zygotic inactivation of multiple genes in mouse through CRISPR/Cas9
      mediated base editing.
AB  - In vivo genetic mutation has become a powerful tool for dissecting gene function;
      however, multi-gene interaction and the compensatory mechanisms involved can make
      findings from single mutations, at best difficult to interpret, and, at worst,
      misleading. Hence, it is necessary to establish an efficient way to disrupt
      multiple genes simultaneously. CRISPR/Cas9-mediated base editing disrupts gene
      function by converting a protein-coding sequence into a stop codon; this is
      referred to as CRISPR-stop. Its application in generating zygotic mutations has
      not been well explored yet. Here, we first performed a proof-of-principle test by
      disrupting Atoh1, a gene crucial for auditory hair cell generation. Next, we
      individually mutated vGlut3 (Slc17a8), otoferlin (Otof) and prestin (Slc26a5),
      three genes needed for normal hearing function. Finally, we successfully
      disrupted vGlut3, Otof and prestin simultaneously. Our results show that CRISPR
      stop can efficiently generate single or triple homozygous F0 mouse mutants,
      bypassing laborious mouse breeding. We believe that CRISPR-stop is a powerful
      method that will pave the way for high-throughput screening of mouse
      developmental and functional genes, matching the efficiency of methods available
      for model organisms such as Drosophila.

PMID- 30275282
TI  - Use of a Metabolic Syndrome Severity Z Score to Track Risk During Treatment of
      Prediabetes: An Analysis of the Diabetes Prevention Program.
AB  - OBJECTIVE: We assessed whether changes in metabolic syndrome (MetS) severity
      during the treatment of prediabetes are associated with reduced risk of type 2
      diabetes mellitus (T2DM) and cardiovascular disease (CVD). RESEARCH DESIGN AND
      METHODS: We analyzed data from the Diabetes Prevention Program (DPP) for 2,476
      adults in 1996-1999 with prediabetes randomized to receive treatment with
      lifestyle modification, metformin, or placebo for 2-3 years and followed through
      2014 for T2DM and CVD outcomes. We calculated effect sizes from baseline in a
      MetS severity z score (MetS-Z) and the individual MetS components, and assessed
      relationships between 1-year effect size and incident T2DM and CVD using hazard
      ratios (HRs) and mediation analysis. RESULTS: Baseline MetS-Z and its components
      were associated with risk of incident T2DM and CVD. During year 1 of
      intervention, MetS-Z and its components decreased most with lifestyle
      modification, followed by treatment with metformin and placebo. Risk of T2DM
      within 1-5 years was most strongly associated with 1-year changes in MetS-Z and
      waist circumference (both HRs for a 1 SD increase = 1.80), whereas the risk of
      CVD was associated with a 1-year change in MetS-Z, glucose, and systolic blood
      pressure. In mediation analyses, the effect of lifestyle modification on T2DM
      risk was mediated by 1-year changes in MetS-Z, waist circumference, glucose, and
      triglycerides, whereas the effect of metformin was mediated by MetS-Z and
      glucose. CONCLUSIONS: Changes in these risk indicators of MetS severity during
      intervention in the DPP reflect altered disease risk and may help in tracking
      earlier responses to treatment and in motivating patients.

PMID- 30275284
TI  - An Automated Grading System for Detection of Vision-Threatening Referable
      Diabetic Retinopathy on the Basis of Color Fundus Photographs.
AB  - OBJECTIVE: The goal of this study was to describe the development and validation
      of an artificial intelligence-based, deep learning algorithm (DLA) for the
      detection of referable diabetic retinopathy (DR). RESEARCH DESIGN AND METHODS: A
      DLA using a convolutional neural network was developed for automated detection of
      vision-threatening referable DR (preproliferative DR or worse, diabetic macular
      edema, or both). The DLA was tested by using a set of 106,244 nonstereoscopic
      retinal images. A panel of ophthalmologists graded DR severity in retinal
      photographs included in the development and internal validation data sets (n =
      71,043); a reference standard grading was assigned once three graders achieved
      consistent grading outcomes. For external validation, we tested our DLA using
      35,201 images of 14,520 eyes (904 eyes with any DR; 401 eyes with vision
      threatening referable DR) from population-based cohorts of Malays, Caucasian
      Australians, and Indigenous Australians. RESULTS: Among the 71,043 retinal images
      in the training and validation data sets, 12,329 showed vision-threatening
      referable DR. In the internal validation data set, the area under the curve
      (AUC), sensitivity, and specificity of the DLA for vision-threatening referable
      DR were 0.989, 97.0%, and 91.4%, respectively. Testing against the independent,
      multiethnic data set achieved an AUC, sensitivity, and specificity of 0.955,
      92.5%, and 98.5%, respectively. Among false-positive cases, 85.6% were due to a
      misclassification of mild or moderate DR. Undetected intraretinal microvascular
      abnormalities accounted for 77.3% of all false-negative cases. CONCLUSIONS: This
      artificial intelligence-based DLA can be used with high accuracy in the detection
      of vision-threatening referable DR in retinal images. This technology offers
      potential to increase the efficiency and accessibility of DR screening programs.

PMID- 30275283
TI  - Atherosclerosis and Microvascular Complications: Results From the Canadian Study
      of Longevity in Type 1 Diabetes.
AB  - OBJECTIVE: Type 1 diabetes carries a significant risk for cardiovascular
      mortality, but it is unclear how atherosclerosis associates with microvascular
      complications. We aimed to determine the relationships between atherosclerotic
      burden and neuropathy, retinopathy, and diabetic kidney disease (DKD) in adults
      with a >=50-year history of type 1 diabetes. RESEARCH DESIGN AND METHODS: Adults
      with type 1 diabetes (n = 69) underwent coronary artery calcification (CAC)
      volume scoring by wide-volume computerized tomography. Microvascular
      complications were graded as follows: neuropathy by clinical assessment,
      electrophysiology, vibration and cooling detection thresholds, heart rate
      variability, and corneal confocal microscopy; retinopathy by ultra-wide-field
      retinal imaging; and DKD by renal hemodynamic function measured by inulin and
      para-aminohippurate clearance at baseline and after intravenous infusion of
      angiotensin II. The cohort was dichotomized to high (>=300 Agatston units [AU])
      or low (<300 AU) CAC and was stratified by diabetes status. A comparator group
      without diabetes (n = 73) matched for age and sex also underwent all study
      procedures except for retinal imaging. RESULTS: CAC scores were higher in
      participants with type 1 diabetes (median Agatston score 1,000 [interquartile
      range = 222, 2,373] AU vs. 1 [0.75] AU in comparators, P < 0.001). In
      participants with type 1 diabetes, high CAC scores associated with markers of
      neuropathy and retinopathy, but not with DKD, or renal hemodynamic function at
      baseline or in response to angiotensin II. CONCLUSIONS: The presence of high CAC
      in adults with longstanding type 1 diabetes was associated with large nerve fiber
      neuropathy and retinopathy but not with renal hemodynamic function, suggesting
      that neuropathy, retinopathy, and macrovascular calcification share common risk
      factors.

PMID- 30275286
TI  - The SNMMI and EANM Procedural Guidelines for Diuresis Renography in Infants and
      Children.

PMID- 30275288
TI  - SNMMI Recognizes Outstanding Contributions at 2018 Annual Meeting.

PMID- 30275289
TI  - FDA Approves AZEDRA Specified Use in Pheochromocytomas/Paragangliomas.

PMID- 30275290
TI  - SNMMI Leadership Update: SNMMI Mid-Winter Meeting in Palm Springs: Focus on
      Cardiovascular Imaging.

PMID- 30275285
TI  - Transcription Factor 7-Like 2 (TCF7L2) Gene Polymorphism and Progression From
      Single to Multiple Autoantibody Positivity in Individuals at Risk for Type 1
      Diabetes.
AB  - OBJECTIVE: The type 2 diabetes-associated alleles at the TCF7L2 locus mark a type
      1 diabetes phenotype characterized by single islet autoantibody positivity as
      well as lower glucose and higher C-peptide measures. Here, we studied whether the
      TCF7L2 locus influences progression of islet autoimmunity, from single to
      multiple (>=2) autoantibody positivity, in relatives of patients with type 1
      diabetes. RESEARCH DESIGN AND METHODS: We evaluated 244 participants in the Type
      1 Diabetes TrialNet Pathway to Prevention study with confirmed single
      autoantibody positivity at screening and Immunochip single nucleotide
      polymorphism data (47.5% male; median age 12.8 years, range 1.2-45.9; 90.2%
      white). We analyzed risk allele frequency at TCF7L2 rs4506565 (in linkage
      disequilibrium with rs7903146). Altogether, 62.6% participants carried >=1 risk
      allele. Univariate and multivariable Cox proportional hazards models and Kaplan
      Meier statistical methods were used. RESULTS: During follow-up (median 5.2 years,
      range 0.2-12.6), 62% of the single autoantibody-positive participants developed
      multiple autoantibody positivity. In the overall cohort, the TCF7L2 locus did not
      significantly predict progression to multiple autoantibody positivity. However,
      among single GAD65 autoantibody-positive participants (n = 158), those who
      carried >=1 risk allele had a lower rate of progression to multiple autoantibody
      positivity (hazard ratio [HR] 0.65, P = 0.033) than those who did not, after
      adjustment for HLA risk haplotypes and age. Among subjects who were either IA-2
      or insulin autoantibody positive only, carrying >=1 TCF7L2 risk allele was not a
      significant factor overall, but in overweight or obese participants, it increased
      the risk of progression to multiple autoantibody positivity (HR 3.02, P = 0.016)
      even with adjustment for age. CONCLUSIONS: The type 2 diabetes-associated TCF7L2
      locus influences progression of islet autoimmunity, with differential effects by
      autoantibody specificity and interaction by obesity/overweight.

PMID- 30275291
TI  - 2018 SNMMI Highlights Lecture: General Nuclear Medicine.

PMID- 30275292
TI  - Correction for Mittal et al., Codon usage influences fitness through RNA
      toxicity.

PMID- 30275293
TI  - Functional muscle recovery with nanoparticle-directed M2 macrophage polarization
      in mice.
AB  - Persistence of inflammation, and associated limits in tissue regeneration, are
      believed to be due in part to the imbalance of M1 over M2 macrophages. Here, we
      hypothesized that providing a sustained source of an antiinflammatory polarizing
      cytokine would shift the balance of macrophages at a site of tissue damage to
      improve functional regeneration. Specifically, IL-4-conjugated gold nanoparticles
      (PA4) were injected into injured murine skeletal muscle, resulting in improved
      histology and an ~40% increase in muscle force compared with mice treated with
      vehicle only. Macrophages were the predominant infiltrating immune cell, and
      treatment with PA4 resulted in an approximately twofold increase in the
      percentage of macrophages expressing the M2a phenotype and an approximately
      twofold decrease in M1 macrophages, compared with mice treated with vehicle only.
      Intramuscular injection of soluble IL-4 did not shift macrophage polarization or
      result in functional muscle improvements. Depletion of monocytes/macrophages
      eliminated the therapeutic effects of PA4, suggesting that improvement in muscle
      function was the result of M2-shifted macrophage polarization. The ability of PA4
      to direct macrophage polarization in vivo may be beneficial in the treatment of
      many injuries and inflammatory diseases.

PMID- 30275295
TI  - Racial disparities in pollution exposure and employment at US industrial
      facilities.
AB  - Proximity to industrial facilities can have positive employment effects as well
      as negative pollution exposure impacts on surrounding communities. Although
      racial disparities in exposure to industrial air pollution in the United States
      are well documented, there has been little empirical investigation of whether
      these disparities are mirrored by employment benefits. We use facility-level data
      from the US Environmental Protection Agency (EPA) Toxics Release Inventory (TRI)
      and the US Equal Employment Opportunity Commission EEO-1 database to assess the
      extent to which the racial and ethnic distribution of industrial employment
      corresponds to the distribution of exposure to air toxics emitted by the same
      facilities. The share of pollution risk accruing to minority groups generally
      exceeds their share of employment and exceeds their share of higher paying jobs
      by a wide margin. We find no evidence that facilities that create higher
      pollution risk for surrounding communities provide more jobs in aggregate.

PMID- 30275294
TI  - Diplogastrellus nematodes are sexually transmitted mutualists that alter the
      bacterial and fungal communities of their beetle host.
AB  - A recent accumulation of studies has demonstrated that nongenetic, maternally
      transmitted factors are often critical to the health and development of offspring
      and can therefore play a role in ecological and evolutionary processes. In
      particular, microorganisms such as bacteria have been championed as heritable,
      symbiotic partners capable of conferring fitness benefits to their hosts. At the
      same time, parents may also pass various nonmicrobial organisms to their
      offspring, yet the roles of such organisms in shaping the developmental
      environment of their hosts remain largely unexplored. Here, we show that the
      nematode Diplogastrellus monhysteroides is transgenerationally inherited and
      sexually transmitted by the dung beetle Onthophagus taurus By manipulating
      artificial chambers in which beetle offspring develop, we demonstrate that the
      presence of D. monhysteroides nematodes enhances the growth of beetle offspring,
      empirically challenging the paradigm that nematodes are merely commensal or even
      detrimental to their insect hosts. Finally, our research presents a compelling
      mechanism whereby the nematodes influence the health of beetle larvae: D.
      monhysteroides nematodes engineer the bacterial and fungal communities that also
      inhabit the beetle developmental chambers, including specific taxa known to be
      involved in biomass degradation, possibly allowing larval beetles better access
      to their otherwise recalcitrant, plant-based diet. Thus, our findings illustrate
      that nongenetic inheritance can include intermediately sized organisms that live
      and proliferate in close association with, and in certain cases enhance, the
      development of their hosts' offspring.

PMID- 30275296
TI  - CXCR6+ST2+ memory T helper 2 cells induced the expression of major basic protein
      in eosinophils to reduce the fecundity of helminth.
AB  - Memory T helper (mTh) cells play important roles in the reinfection of pathogens
      and drive the pathogenesis of diseases. While recent studies have characterized
      the pathogenic mTh2 cell subpopulations driving allergic inflammation, those that
      induce immune responses against helminth infection remain unknown. We found that
      IL-5-producing CXCR6+ST2+CD44+ mTh2 cells play a crucial role in the IL-33
      dependent inhibition of the fecundity of helminth, whereas other ST2- mTh2 cells
      do not. Although both cell types induced the infiltration of granulocytes,
      especially eosinophils, into the lungs in response to helminth infection, the
      ST2+ mTh2 cell-induced eosinophils expressed higher levels of major basic protein
      (MBP), which is important for reducing the fecundity of Nippostrongylus
      brasiliensis (Nb), than ST2- mTh2 cell-induced ones. Notably, we also found that
      ST2+ Treg cells but not ST2- Treg cells suppressed CXCR6+ST2+ mTh2 cell-mediated
      immune responses. Taken together, these findings show that we identified a
      mechanism against helminth elicited by a subpopulation of IL-5-producing mTh2
      cells through the accumulation of eosinophils strongly expressing MBP in the
      lungs.

PMID- 30275297
TI  - Copper inhibits peptidoglycan LD-transpeptidases suppressing beta-lactam
      resistance due to bypass of penicillin-binding proteins.
AB  - The peptidoglycan (PG) layer stabilizes the bacterial cell envelope to maintain
      the integrity and shape of the cell. Penicillin-binding proteins (PBPs)
      synthesize essential 4-3 cross-links in PG and are inhibited by beta-lactam
      antibiotics. Some clinical isolates and laboratory strains of Enterococcus
      faecium and Escherichia coli achieve high-level beta-lactam resistance by
      utilizing beta-lactam-insensitive LD-transpeptidases (LDTs) to produce
      exclusively 3-3 cross-links in PG, bypassing the PBPs. In E. coli, other LDTs
      covalently attach the lipoprotein Lpp to PG to stabilize the envelope and
      maintain the permeability barrier function of the outermembrane. Here we show
      that subminimal inhibitory concentration of copper chloride sensitizes E. coli
      cells to sodium dodecyl sulfate and impair survival upon LPS transport stress,
      indicating reduced cell envelope robustness. Cells grown in the presence of
      copper chloride lacked 3-3 cross-links in PG and displayed reduced covalent
      attachment of Braun's lipoprotein and reduced incorporation of a fluorescent d
      amino acid, suggesting inhibition of LDTs. Copper dramatically decreased the
      minimal inhibitory concentration of ampicillin in E. coli and E. faecium strains
      with a resistance mechanism relying on LDTs and inhibited purified LDTs at
      submillimolar concentrations. Hence, our work reveals how copper affects
      bacterial cell envelope stability and counteracts LDT-mediated beta-lactam
      resistance.

PMID- 30275299
TI  - Tradeoffs in environmental and equity gains from job accessibility.
AB  - Increasing job accessibility is considered key to urban sustainability progress,
      both from an environmental and from a social perspective. However, sustainability
      outcomes depend on the processes contributing to accessibility trends, not just
      the trends themselves. Here, we ask whether sustainability benefits have followed
      from accessibility trends in the United States. We measure changes in
      accessibility from 2002 to 2014 across 909 US urban areas and decompose these
      changes to understand underlying infrastructure and land use processes. Our
      results show that job accessibility has increased across 74% of urban areas for
      the average resident, using both cars and transit. However, most of these
      accessibility gains were not achieved in ways that are inherently beneficial to
      environmental or social sustainability. In some urban areas, accessibility
      increases were conducive to reducing emissions, while in others, accessibility
      increases were conducive to reducing social inequities. However, accessibility
      increases almost never created a simultaneous social and environmental "win-win,"
      as is often assumed. Our findings highlight how the spatial patterns of
      urbanization create tradeoffs between different facets of sustainability.
      Identifying where social objectives take precedence over environmental objectives
      (or vice versa) could help determine how accessibility increases can be
      accomplished to contribute to a more sustainable urban future.

PMID- 30275298
TI  - Two are better than one: Infant language learning from video improves in the
      presence of peers.
AB  - Studies show that young children learn new phonemes and words from humans
      significantly better than from machines. However, it is not clear why learning
      from video is ineffective or what might be done to improve learning from a
      screen. The present study, conducted with 9-month-old infants, utilized a
      manipulation-touch screen video-which allowed infants to control presentations of
      foreign-language video clips. We tested the hypothesis that infant learning from
      a screen would be enhanced in the presence of a peer, as opposed to learning
      alone. Brain measures of phonetic learning and detailed analyses of interaction
      during learning confirm the hypothesis that social partners enhance learning,
      even from screens.

PMID- 30275300
TI  - HSP90 is a chaperone for DLK and is required for axon injury signaling.
AB  - Peripheral nerve injury induces a robust proregenerative program that drives axon
      regeneration. While many regeneration-associated genes are known, the mechanisms
      by which injury activates them are less well-understood. To identify such
      mechanisms, we performed a loss-of-function pharmacological screen in cultured
      adult mouse sensory neurons for proteins required to activate this program. Well
      characterized inhibitors were present as injury signaling was induced but were
      removed before axon outgrowth to identify molecules that block induction of the
      program. Of 480 compounds, 35 prevented injury-induced neurite regrowth. The top
      hits were inhibitors to heat shock protein 90 (HSP90), a chaperone with no known
      role in axon injury. HSP90 inhibition blocks injury-induced activation of the
      proregenerative transcription factor cJun and several regeneration-associated
      genes. These phenotypes mimic loss of the proregenerative kinase, dual leucine
      zipper kinase (DLK), a critical neuronal stress sensor that drives axon
      degeneration, axon regeneration, and cell death. HSP90 is an atypical chaperone
      that promotes the stability of signaling molecules. HSP90 and DLK show two
      hallmarks of HSP90-client relationships: (i) HSP90 binds DLK, and (ii) HSP90
      inhibition leads to rapid degradation of existing DLK protein. Moreover, HSP90 is
      required for DLK stability in vivo, where HSP90 inhibitor reduces DLK protein in
      the sciatic nerve. This phenomenon is evolutionarily conserved in Drosophila
      Genetic knockdown of Drosophila HSP90, Hsp83, decreases levels of Drosophila DLK,
      Wallenda, and blocks Wallenda-dependent synaptic terminal overgrowth and injury
      signaling. Our findings support the hypothesis that HSP90 chaperones DLK and is
      required for DLK functions, including proregenerative axon injury signaling.

PMID- 30275301
TI  - Measures of single- versus multiple-round translation argue against a mechanism
      to ensure coupling of transcription and translation.
AB  - In prokaryotes, the synthesis of RNA and protein occurs simultaneously in the
      cytoplasm. A number of studies indicate that translation can strongly impact
      transcription, a phenomenon often attributed to physical coupling between RNA
      polymerase (RNAP) and the lead ribosome on the nascent mRNA. Whether there
      generally exists a mechanism to ensure or promote RNAP-ribosome coupling remains
      unclear. Here, we used an efficient hammerhead ribozyme and developed a reporter
      system to measure single- versus multiple-round translation in Escherichia coli
      Six pairs of cotranscribed and differentially translated genes were analyzed. For
      five of them, the stoichiometry of the two protein products came no closer to
      unity (1:1) when the rounds of translation were severely reduced in wild-type
      cells. Introduction of mutation rpoB(I572N), which slows RNAP elongation, could
      promote coupling, as indicated by stoichiometric SspA and SspB products in the
      single-round assay. These data are consistent with models of stochastic coupling
      in which the probability of coupling depends on the relative rates of
      transcription and translation and suggest that RNAP often transcribes without a
      linked ribosome.

PMID- 30275302
TI  - Space radiation triggers persistent stress response, increases senescent
      signaling, and decreases cell migration in mouse intestine.
AB  - Proliferative gastrointestinal (GI) tissue is radiation-sensitive, and heavy-ion
      space radiation with its high-linear energy transfer (high-LET) and higher
      damaging potential than low-LET gamma-rays is predicted to compromise astronauts'
      GI function. However, much uncertainty remains in our understanding of how heavy
      ions affect coordinated epithelial cell migration and extrusion, which are
      essential for GI homeostasis. Here we show using mouse small intestine as a model
      and BrdU pulse labeling that cell migration along the crypt-villus axis is
      persistently decreased after a low dose of heavy-ion 56Fe radiation relative to
      control and gamma-rays. Wnt/beta-catenin and its downstream EphrinB/EphB
      signaling are key to intestinal epithelial cell (IEC) proliferation and
      positioning during migration, and both are up-regulated after 56Fe radiation.
      Conversely, factors involved in cell polarity and adhesion and cell-extracellular
      matrix interactions were persistently down-regulated after 56Fe irradiation
      potentially altering cytoskeletal remodeling and cell extrusion. 56Fe radiation
      triggered a time-dependent increase in gammaH2AX foci and senescent cells but
      without a noticeable increase in apoptosis. Some senescent cells acquired the
      senescence-associated secretory phenotype, and this was accompanied by increased
      IEC proliferation, implying a role for progrowth inflammatory factors.
      Collectively, this study demonstrates a unique phenomenon of heavy-ion radiation
      induced persistently delayed IEC migration involving chronic sublethal genotoxic
      and oncogenic stress-induced altered cytoskeletal dynamics, which were seen even
      a year later. When considered along with changes in barrier function and nutrient
      absorption factors as well as increased intestinal tumorigenesis, our in vivo
      data raise a serious concern for long-duration deep-space manned missions.

PMID- 30275303
TI  - Effect of sequential video shot comprehensibility on attentional synchrony: A
      comparison of children and adults.
AB  - To comprehend edited video, viewers must infer the meaning conveyed by successive
      video shots (i.e., continuous video segments separated by edit points, such as
      camera cuts). The central question here was whether comprehension-related top
      down cognitive processes drive eye movements during sequential processing of
      video montage. Eye movements were recorded as 4 year olds and adults (n = 62)
      watched a video with the same constituent shots in either normal or random
      sequence. The key analyses compared eye movements to constituent shots when
      presented in normal order with those to the same shots presented in random order.
      The dependent variable was attentional synchrony or the extent to which viewers
      looked at the same location at the same time, indicating commonality of
      processing the video. This was calculated as the bivariate contour ellipse area
      within which points of gaze fell during each video frame. Results indicated that
      children were more scattered in their gaze locations than adults. Viewers became
      more similar to each other as normal vignettes unfolded over time; this was
      especially true in adults and possibly reflects a growing and shared
      understanding of the content. Conversely, adult attentional synchrony was reduced
      when watching random shot sequences. Thus, attentional synchrony during normal
      video viewing is driven not only by salient visual features, such as movement and
      areas of high contrast, but also, by the unfolding sequential comprehension of
      video montage, especially in adults. Differences between children and adults
      indicate that this top-down control of eye movements while watching video changes
      systematically over development.

PMID- 30275305
TI  - Correction to Supporting Information for Reid-Bayliss and Loeb, Accurate RNA
      consensus sequencing for high-fidelity detection of transcriptional mutagenesis
      induced epimutations.

PMID- 30275304
TI  - Maize yields over Europe may increase in spite of climate change, with an
      appropriate use of the genetic variability of flowering time.
AB  - Projections based on invariant genotypes and agronomic practices indicate that
      climate change will largely decrease crop yields. The comparatively few studies
      considering farmers' adaptation result in a diversity of impacts depending on
      their assumptions. We combined experiments and process-based modeling for
      analyzing the consequences of climate change on European maize yields if farmers
      made the best use of the current genetic variability of cycle duration, based on
      practices they currently use. We first showed that the genetic variability of
      maize flowering time is sufficient for identifying a cycle duration that
      maximizes yield in a range of European climatic conditions. This was observed in
      six field experiments with a panel of 121 accessions and extended to 59 European
      sites over 36 years with a crop model. The assumption that farmers use optimal
      cycle duration and sowing date was supported by comparison with historical data.
      Simulations were then carried out for 2050 with 3 million combinations of crop
      cycle durations, climate scenarios, management practices, and modeling
      hypotheses. Simulated grain production over Europe in 2050 was stable (-1 to +1%)
      compared with the 1975-2010 baseline period under the hypotheses of unchanged
      cycle duration, whereas it was increased (+4-7%) when crop cycle duration and
      sowing dates were optimized in each local environment. The combined effects of
      climate change and farmer adaptation reduced the yield gradient between south and
      north of Europe and increased European maize production if farmers continued to
      make the best use of the genetic variability of crop cycle duration.

PMID- 30275306
TI  - Metaanalysis of the relationship between violent video game play and physical
      aggression over time.
AB  - To clarify and quantify the influence of video game violence (VGV) on aggressive
      behavior, we conducted a metaanalysis of all prospective studies to date that
      assessed the relation between exposure to VGV and subsequent overt physical
      aggression. The search strategy identified 24 studies with over 17,000
      participants and time lags ranging from 3 months to 4 years. The samples
      comprised various nationalities and ethnicities with mean ages from 9 to 19
      years. For each study we obtained the standardized regression coefficient for the
      prospective effect of VGV on subsequent aggression, controlling for baseline
      aggression. VGV was related to aggression using both fixed [beta = 0.113, 95% CI
      = (0.098, 0.128)] and random effects models [beta = 0.106 (0.078, 0.134)]. When
      all available covariates were included, the size of the effect remained
      significant for both models [beta = 0.080 (0.065, 0.094) and beta = 0.078 (0.053,
      0.102), respectively]. No evidence of publication bias was found. Ethnicity was a
      statistically significant moderator for the fixed-effects models (P <= 0.011) but
      not for the random-effects models. Stratified analyses indicated the effect was
      largest among Whites, intermediate among Asians, and nonsignificant among
      Hispanics. Discussion focuses on the implications of such findings for current
      debates regarding the effects of violent video games on physical aggression.

PMID- 30275307
TI  - Mutations in the DNA demethylase OsROS1 result in a thickened aleurone and
      improved nutritional value in rice grains.
AB  - The rice endosperm, consisting of an outer single-cell layer aleurone and an
      inner starchy endosperm, is an important staple food for humans. While starchy
      endosperm stores mainly starch, the aleurone is rich in an array of proteins,
      vitamins, and minerals. To improve the nutritional value of rice, we screened for
      mutants with thickened aleurones using a half-seed assay and identified thick
      aleurone 2-1 (ta2-1), in which the aleurone has 4.8 +/- 2.2 cell layers on
      average. Except for starch, the contents of all measured nutritional factors,
      including lipids, proteins, vitamins, minerals, and dietary fibers, were
      increased in ta2-1 grains. Map-based cloning showed that TA2 encodes the DNA
      demethylase OsROS1. A point mutation in the 14th intron of OsROS1 led to
      alternative splicing that generated an extra transcript, mOsROS1, with a 21-nt
      insertion from the intron. Genetic analyses showed that the ta2-1 phenotype is
      inherited with an unusual gametophytic maternal effect, which is caused not by
      imprinted gene expression but rather by the presence of the mOsROS1 transcript.
      Five additional ta2 alleles with the increased aleurone cell layer and different
      inheritance patterns were identified by TILLING. Genome-wide bisulfite sequencing
      revealed general increases in CG and CHG methylations in ta2-1 endosperms, along
      with hypermethylation and reduced expression in two putative aleurone
      differentiation-related transcription factors. This study thus suggests that
      OsROS1-mediated DNA demethylation restricts the number of aleurone cell layers in
      rice and provides a way to improve the nutrition of rice.

PMID- 30275308
TI  - Bypassing a 8,5'-cyclo-2'-deoxyadenosine lesion by human DNA polymerase eta at
      atomic resolution.
AB  - Oxidatively induced DNA lesions 8,5'-cyclopurine-2'-deoxynucleosides (cdPus) are
      prevalent and cytotoxic by impeding DNA replication and transcription. Both the
      5'R- and 5'S-diastereomers of cdPu can be removed by nucleotide excision repair;
      however, the 5'S-cdPu is more resistant to repair than the 5'R counterpart. Here,
      we report the crystal structures of human polymerase (Pol) eta bypassing 5'S-8,5'
      cyclo-2'-deoxyadenosine (cdA) in insertion and the following two extension steps.
      The cdA-containing DNA structures vary in response to the protein environment.
      Supported by the "molecular splint" of Pol eta, the structure of 5'S-cdA at 1.75
      A resolution reveals that the backbone is pinched toward the minor groove and the
      adenine base is tilted. In the templating position, the cdA takes up the extra
      space usually reserved for the thymine dimer, and dTTP is efficiently
      incorporated by Pol eta in the presence of Mn2+ Rigid distortions of the DNA
      duplex by cdA, however, prevent normal base pairing and hinder immediate primer
      extension by Pol eta. Our results provide structural insights into the strong
      replication blockage effect and the mutagenic property of the cdPu lesions in
      cells.

PMID- 30275310
TI  - Bayesian approach to SETI.
AB  - The search for technosignatures from hypothetical galactic civilizations is going
      through a new phase of intense activity. For the first time, a significant
      fraction of the vast search space is expected to be sampled in the foreseeable
      future, potentially bringing informative data about the abundance of detectable
      extraterrestrial civilizations or the lack thereof. Starting from the current
      state of ignorance about the galactic population of nonnatural electromagnetic
      signals, we formulate a Bayesian statistical model to infer the mean number of
      radio signals crossing Earth, assuming either nondetection or the detection of
      signals in future surveys of the Galaxy. Under fairly noninformative priors, we
      find that not detecting signals within about 1 kly from Earth, while suggesting
      the lack of galactic emitters or at best the scarcity thereof, is nonetheless
      still consistent with a probability exceeding 10% that typically over [Formula:
      see text] signals could be crossing Earth, with radiated power analogous to that
      of the Arecibo radar, but coming from farther in the Milky Way. The existence in
      the Galaxy of potentially detectable Arecibo-like emitters can be reasonably
      ruled out only if all-sky surveys detect no such signals up to a radius of about
      40 kly, an endeavor requiring detector sensitivities thousands times higher than
      those of current telescopes. Conversely, finding even one Arecibo-like signal
      within [Formula: see text] light years, a possibility within reach of current
      detectors, implies almost certainly that typically more than [Formula: see text]
      signals of comparable radiated power cross the Earth, yet to be discovered.

PMID- 30275309
TI  - Lesion network localization of free will.
AB  - Our perception of free will is composed of a desire to act (volition) and a sense
      of responsibility for our actions (agency). Brain damage can disrupt these
      processes, but which regions are most important for free will perception remains
      unclear. Here, we study focal brain lesions that disrupt volition, causing
      akinetic mutism (n = 28), or disrupt agency, causing alien limb syndrome (n =
      50), to better localize these processes in the human brain. Lesion locations
      causing either syndrome were highly heterogeneous, occurring in a variety of
      different brain locations. We next used a recently validated technique termed
      lesion network mapping to determine whether these heterogeneous lesion locations
      localized to specific brain networks. Lesion locations causing akinetic mutism
      all fell within one network, defined by connectivity to the anterior cingulate
      cortex. Lesion locations causing alien limb fell within a separate network,
      defined by connectivity to the precuneus. Both findings were specific for these
      syndromes compared with brain lesions causing similar physical impairments but
      without disordered free will. Finally, our lesion-based localization matched
      network localization for brain stimulation locations that disrupt free will and
      neuroimaging abnormalities in patients with psychiatric disorders of free will
      without overt brain lesions. Collectively, our results demonstrate that lesions
      in different locations causing disordered volition and agency localize to unique
      brain networks, lending insight into the neuroanatomical substrate of free will
      perception.

PMID- 30275311
TI  - Early adolescent Rai1 reactivation reverses transcriptional and social
      interaction deficits in a mouse model of Smith-Magenis syndrome.
AB  - Haploinsufficiency of Retinoic Acid Induced 1 (RAI1) causes Smith-Magenis
      syndrome (SMS), a syndromic autism spectrum disorder associated with craniofacial
      abnormalities, intellectual disability, and behavioral problems. There is
      currently no cure for SMS. Here, we generated a genetic mouse model to determine
      the reversibility of SMS-like neurobehavioral phenotypes in Rai1 heterozygous
      mice. We show that normalizing the Rai1 level 3-4 wk after birth corrected the
      expression of genes related to neural developmental pathways and fully reversed a
      social interaction deficit caused by Rai1 haploinsufficiency. In contrast, Rai1
      reactivation 7-8 wk after birth was not beneficial. We also demonstrated that the
      correct Rai1 dose is required in both excitatory and inhibitory neurons for
      proper social interactions. Finally, we found that Rai1 heterozygous mice
      exhibited a reduction of dendritic spines in the medial prefrontal cortex (mPFC)
      and that optogenetic activation of mPFC neurons in adults improved the social
      interaction deficit of Rai1 heterozygous mice. Together, these results suggest
      the existence of a postnatal temporal window during which restoring Rai1 can
      improve the transcriptional and social behavioral deficits in a mouse model of
      SMS. It is possible that circuit-level interventions would be beneficial beyond
      this critical window.

PMID- 30275312
TI  - Minds and brains of media multitaskers: Current findings and future directions.
AB  - Media and technology are ubiquitous elements of our daily lives, and their use
      can offer many benefits and rewards. At the same time, decisions about how
      individuals structure their use of media can be informed by consideration of
      whether, and if so how, the mind and brain are shaped by different use patterns.
      Here we review the growing body of research that investigates the cognitive and
      neural profiles of individuals who differ in the extent to which they
      simultaneously engage with multiple media streams, or "media multitasking." While
      the literature is still sparse, and is marked by both convergent and divergent
      findings, the balance of evidence suggests that heavier media multitaskers
      exhibit poorer performance in a number of cognitive domains, relative to lighter
      media multitaskers (although many studies find no performance differences between
      groups). When evidence points to a relationship between media multitasking level
      and cognition, it is often on tasks that require or are influenced by
      fluctuations in sustained goal-directed attention. Given the real-world
      significance of such findings, further research is needed to uncover the
      mechanistic underpinnings of observed differences, to determine the direction of
      causality, to understand whether remediation efforts are needed and effective,
      and to determine how measurement heterogeneity relates to variable outcomes. Such
      efforts will ultimately inform decisions about how to minimize the potential
      costs and maximize the many benefits of our ever-evolving media landscape.

PMID- 30275313
TI  - Changes in resource partitioning between and within organs support growth
      adjustment to neighbor proximity in Brassicaceae seedlings.
AB  - In shade-intolerant plants, the perception of proximate neighbors rapidly induces
      architectural changes resulting in elongated stems and reduced leaf size. Sensing
      and signaling steps triggering this modified growth program have been identified.
      However, the underlying changes in resource allocation that fuel stem growth
      remain poorly understood. Through 14CO2 pulse labeling of Brassica rapa
      seedlings, we show that perception of the neighbor detection signal, low ratio of
      red to far-red light (R:FR), leads to increased carbon allocation from the major
      site of photosynthesis (cotyledons) to the elongating hypocotyl. While carbon
      fixation and metabolite levels remain similar in low R:FR, partitioning to all
      downstream carbon pools within the hypocotyl is increased. Genetic analyses using
      Arabidopsis thaliana mutants indicate that low-R:FR-induced hypocotyl elongation
      requires sucrose transport from the cotyledons and is regulated by a PIF7
      dependent metabolic response. Moreover, our data suggest that starch metabolism
      in the hypocotyl has a growth-regulatory function. The results reveal a key
      mechanism by which metabolic adjustments can support rapid growth adaptation to a
      changing environment.

PMID- 30275314
TI  - Natural forcing of the North Atlantic nitrogen cycle in the Anthropocene.
AB  - Human alteration of the global nitrogen cycle intensified over the 1900s. Model
      simulations suggest that large swaths of the open ocean, including the North
      Atlantic and the western Pacific, have already been affected by anthropogenic
      nitrogen through atmospheric transport and deposition. Here we report an ~130
      year-long record of the 15N/14N of skeleton-bound organic matter in a coral from
      the outer reef of Bermuda, which provides a test of the hypothesis that
      anthropogenic atmospheric nitrogen has significantly augmented the nitrogen
      supply to the open North Atlantic surface ocean. The Bermuda 15N/14N record does
      not show a long-term decline in the Anthropocene of the amplitude predicted by
      model simulations or observed in a western Pacific coral 15N/14N record. Rather,
      the decadal variations in the Bermuda 15N/14N record appear to be driven by the
      North Atlantic Oscillation, most likely through changes in the formation rate of
      Subtropical Mode Water. Given that anthropogenic nitrogen emissions have been
      decreasing in North America since the 1990s, this study suggests that in the
      coming decades, the open North Atlantic will remain minimally affected by
      anthropogenic nitrogen deposition.

PMID- 30275315
TI  - How to play 20 questions with nature and lose: Reflections on 100 years of brain
      training research.
AB  - Despite dozens of empirical studies and a growing body of meta-analytic work,
      there is little consensus regarding the efficacy of cognitive training. In this
      review, we examine why this substantial corpus has failed to answer the often
      asked question, "Does cognitive training work?" We first define cognitive
      training and discuss the general principles underlying training interventions.
      Next, we review historical interventions and discuss how findings from this early
      work remain highly relevant for current cognitive-training research. We highlight
      a variety of issues preventing real progress in understanding the underlying
      mechanisms of training, including the lack of a coherent theoretical framework to
      guide training research and methodological issues across studies and meta
      analyses. Finally, suggestions for correcting these issues are offered in the
      hope that we might make greater progress in the next 100 y of cognitive-training
      research.

PMID- 30275316
TI  - Entropically driven aggregation of bacteria by host polymers promotes antibiotic
      tolerance in Pseudomonas aeruginosa.
AB  - Bacteria causing chronic infections are generally observed living in cell
      aggregates suspended in polymer-rich host secretions, and bacterial phenotypes
      induced by aggregated growth may be key factors in chronic infection
      pathogenesis. Bacterial aggregation is commonly thought of as a consequence of
      biofilm formation; however the mechanisms producing aggregation in vivo remain
      unclear. Here we show that polymers that are abundant at chronic infection sites
      cause bacteria to aggregate by the depletion aggregation mechanism, which does
      not require biofilm formation functions. Depletion aggregation is mediated by
      entropic forces between uncharged or like-charged polymers and particles (e.g.,
      bacteria). Our experiments also indicate that depletion aggregation of bacteria
      induces marked antibiotic tolerance that was dependent on the SOS response, a
      stress response activated by genotoxic stress. These findings raise the
      possibility that targeting conditions that promote depletion aggregation or
      mechanisms of depletion-mediated tolerance could lead to new therapeutic
      approaches to combat chronic bacterial infections.

PMID- 30275317
TI  - Role of PDGF receptor-alpha during human cytomegalovirus entry into fibroblasts.
AB  - Human CMV (HCMV) exhibits a broad cell tropism that depends on two virion
      glycoprotein complexes: a trimeric complex (gH/gL/gO) that facilitates viral
      infection primarily in fibroblasts and a pentameric complex (gH/gL/pUL128-pUL130
      pUL131A) that mediates infection in epithelial and endothelial cells. We
      performed genome-wide CRISPR screens in which the PDGF receptor-alpha
      (PDGFRalpha) was identified as the most significant cellular gene product
      essential for infection by HCMV virions containing only trimeric complex (trimer
      only virus). Trimer-only virus did not enter PDGFRalpha knockout fibroblasts. By
      using knockout fibroblasts, the extracellular domain of PDGFRalpha required for
      virus entry was mapped, and the intracellular tyrosine kinase domain was shown to
      be nonessential. In addition, direct cell-to-cell spread of virus from knockout
      cells transfected with trimer-only viral DNA was blocked, despite the production
      of infectious virus in the transfected cells. In contrast to trimer-only virus,
      wild-type HCMV virions containing both trimeric and pentameric complexes entered
      PDGFRalpha knockout cells, reinforcing the view that fibroblasts contain a
      second, independent receptor for the pentameric complex. Importantly, however,
      wild-type virus entered the knockout fibroblasts at reduced efficiency compared
      with parental fibroblasts, arguing that the cellular receptor for the virion
      pentameric complex is limiting or that virions are produced containing different
      relative amounts of the two glycoprotein complexes. Finally, ectopic expression
      of PDGFRalpha in ARPE-19 epithelial cells and THP-1 monocytic cells, which have
      little to no endogenous PDGFRalpha expression, markedly enhanced their
      susceptibility to trimer-only virions. In sum, our data clarify several key
      determinants of HCMV tropism.

PMID- 30275318
TI  - Screen media use and ADHD-related behaviors: Four decades of research.
AB  - The diagnosis of attention-deficit/hyperactivity disorder (ADHD) among children
      and adolescents has increased considerably over the past decades. Scholars and
      health professionals alike have expressed concern about the role of screen media
      in the rise in ADHD diagnosis. However, the extent to which screen media use and
      ADHD are linked remains a point of debate. To understand the current state of the
      field and, ultimately, move the field forward, we provide a systematic review of
      the literature on the relationship between children and adolescents' screen media
      use and ADHD-related behaviors (i.e., attention problems, hyperactivity, and
      impulsivity). Using the Differential Susceptibility to Media effects Model as a
      theoretical lens, we systematically organize the existing literature, identify
      potential shortcomings in this literature, and provide directions for future
      research. The available evidence suggests a statistically small relationship
      between media and ADHD-related behaviors. Evidence also suggests that individual
      child differences, such as gender and trait aggression, may moderate this
      relationship. There is a clear need for future research that investigates
      causality, underlying mechanisms, and differential susceptibility to the effects
      of screen media use on ADHD-related behaviors. It is only through a richer
      empirical body that we will be able to fully understand the media-ADHD
      relationship.

PMID- 30275320
TI  - Unique size-dependent nanocatalysis revealed at the single atomically precise
      gold cluster level.
AB  - Atomically precise metal clusters have attracted increasing interest owing to
      their unique size-dependent properties; however, little has been known about the
      effect of size on the catalytic properties of metal clusters at the single
      cluster level. Here, by real-time monitoring with single-molecule fluorescence
      microscopy the size-dependent catalytic process of individual Au clusters at
      single-turnover resolution, we study the size-dependent catalytic behaviors of
      gold (Au) clusters at the single-cluster level, and then observe the strong size
      effect on the catalytic properties of individual Au clusters, in both catalytic
      product formation and dissociation processes. Surprisingly, indicated by both
      experiments and density functional theory (DFT) calculations, due to such a
      unique size effect, besides observing the different product dissociation
      behaviors on different-sized Au clusters, we also observe that small Au clusters
      [i.e., Au15(MPA)13; here, MPA denotes 3-mercaptopropionic acid] catalyze the
      product formation through a competitive Langmuir-Hinshelwood mechanism, while
      those relatively larger Au clusters [e.g., Au18(MPA)14 and Au25(MPA)18] or
      nanoparticles catalyze the same process through a noncompetitive Langmuir
      Hinshelwood mechanism. Such a size effect on the nanocatalysis could be
      attributed intrinsically to the size-dependent electronic structure of Au
      clusters. Further analysis of dynamic activity fluctuation of Au clusters reveals
      more different catalytic properties between Au clusters and traditional Au
      nanoparticles due to their different size-dependent structures.

PMID- 30275321
TI  - From savannas to blue-phase LCD screens: Prospects and perils for child
      development in the Post-Modern Digital Information Age.

PMID- 30275319
TI  - How early media exposure may affect cognitive function: A review of results from
      observations in humans and experiments in mice.
AB  - Attention deficit hyperactivity disorder (ADHD) is now among the most commonly
      diagnosed chronic psychological dysfunctions of childhood. By varying estimates,
      it has increased by 30% in the past 20 years. Environmental factors that might
      explain this increase have been explored. One such factor may be audiovisual
      media exposure during early childhood. Observational studies in humans have
      linked exposure to fast-paced television in the first 3 years of life with
      subsequent attentional deficits in later childhood. Although longitudinal and
      well controlled, the observational nature of these studies precludes definitive
      conclusions regarding a causal relationship. As experimental studies in humans
      are neither ethical nor practical, mouse models of excessive sensory stimulation
      (ESS) during childhood, akin to the enrichment studies that have previously shown
      benefits of stimulation in rodents, have been developed. Experimental studies
      using this model have corroborated that ESS leads to cognitive and behavioral
      deficits, some of which may be potentially detrimental. Given the ubiquity of
      media during childhood, these findings in humansand rodents perhaps have
      important implications for public health.

PMID- 30275322
TI  - FtsZ filaments have the opposite kinetic polarity of microtubules.
AB  - FtsZ is the ancestral homolog of tubulin and assembles into the Z ring that
      organizes the division machinery to drive cell division in most bacteria. In
      contrast to tubulin that assembles into 13 stranded microtubules that undergo
      dynamic instability, FtsZ assembles into single-stranded filaments that treadmill
      to distribute the peptidoglycan synthetic machinery at the septum. Here, using
      longitudinal interface mutants of FtsZ, we demonstrate that the kinetic polarity
      of FtsZ filaments is opposite to that of microtubules. A conformational switch
      accompanying the assembly of FtsZ generates the kinetic polarity of FtsZ
      filaments, which explains the toxicity of interface mutants that function as a
      capper and reveals the mechanism of cooperative assembly. This approach can also
      be employed to determine the kinetic polarity of other filament-forming proteins.

PMID- 30275323
TI  - Drought losses in China might double between the 1.5  degrees C and 2.0  degrees
      C warming.
AB  - We project drought losses in China under global temperature increase of 1.5 
      degrees C and 2.0  degrees C, based on the Standardized Precipitation
      Evapotranspiration Index (SPEI) and the Palmer Drought Severity Index (PDSI), a
      cluster analysis method, and "intensity-loss rate" function. In contrast to
      earlier studies, to project the drought losses, we predict the regional gross
      domestic product under shared socioeconomic pathways instead of using a static
      socioeconomic scenario. We identify increasing precipitation and
      evapotranspiration pattern for the 1.5  degrees C and 2.0  degrees C global
      warming above the preindustrial at 2020-2039 and 2040-2059, respectively. With
      increasing drought intensity and areal coverage across China, drought losses will
      soar. The estimated loss in a sustainable development pathway at the 1.5  degrees
      C warming level increases 10-fold in comparison with the reference period 1986
      2005 and nearly threefold relative to the interval 2006-2015. However, limiting
      the temperature increase to 1.5  degrees C can reduce the annual drought losses
      in China by several tens of billions of US dollars, compared with the 2.0 
      degrees C warming.

PMID- 30275324
TI  - Natural molecules induce and synergize to boost expression of the human
      antimicrobial peptide beta-defensin-3.
AB  - Antimicrobial peptides (AMPs) are mucosal defense effectors of the human innate
      immune response. In the intestine, AMPs are produced and secreted by epithelial
      cells to protect the host against pathogens and to support homeostasis with
      commensals. The inducible nature of AMPs suggests that potent inducers could be
      used to increase their endogenous expression for the prevention or treatment of
      diseases. Here we aimed at identifying molecules from the natural pharmacopoeia
      that induce expression of human beta-defensin-3 (HBD3), one of the most efficient
      AMPs, without modifying the production of proinflammatory cytokines. By
      screening, we identified three molecules isolated from medicinal plants,
      andrographolide, oridonin, and isoliquiritigenin, which induced HBD3 production
      in human colonic epithelial cells. This effect was observed without activation of
      the NF-kappaB pathway or the expression of associated proinflammatory cytokines.
      We identified the EGF receptor as the target of these compounds and characterized
      the downstream-activated MAPK pathways. At the chromatin level, molecules
      increased phosphorylation of histone H3 on serine S10 and recruitment of the c
      Fos, c-Jun, and Elk1 or c-Myc transcription factors at the HBD3 promoter.
      Interestingly, stimulating cells with a combination of andrographolide and
      isoliquiritigenin synergistically enhanced HBD3 induction 10-fold more than
      observed with each molecule alone. Finally, we investigated the molecular basis
      governing the synergistic effect, confirmed our findings in human colonic primary
      cells, and demonstrated that synergism increased cellular antimicrobial activity.
      This work shows the capability of small molecules to achieve induction of
      epithelial antimicrobial defenses while simultaneously avoiding the deleterious
      risks of an inflammatory response.

PMID- 30275325
TI  - Mercury isotope signatures record photic zone euxinia in the Mesoproterozoic
      ocean.
AB  - Photic zone euxinia (PZE) is a condition where anoxic, H2S-rich waters occur in
      the photic zone (PZ). PZE has been invoked as an impediment to the evolution of
      complex life on early Earth and as a kill mechanism for Phanerozoic mass
      extinctions. Here, we investigate the potential application of mercury (Hg)
      stable isotopes in marine sedimentary rocks as a proxy for PZE by measuring Hg
      isotope compositions in late Mesoproterozoic (~1.1 Ga) shales that have
      independent evidence of PZE during discrete intervals. Strikingly, a
      significantly negative shift of Hg mass-independent isotope fractionation (MIF)
      was observed during euxinic intervals, suggesting changes in Hg sources or
      transformations in oceans coincident with the development of PZE. We propose that
      the negative shift of Hg MIF was most likely caused by (i) photoreduction of
      Hg(II) complexed by reduced sulfur ligands in a sulfide-rich PZ, and (ii)
      enhanced sequestration of atmospheric Hg(0) to the sediments by thiols and
      sulfide that were enriched in the surface ocean as a result of PZE. This study
      thus demonstrates that Hg isotope compositions in ancient marine sedimentary
      rocks can be a promising proxy for PZE and therefore may provide valuable
      insights into changes in ocean chemistry and its impact on the evolution of life.

PMID- 30275326
TI  - Cytoprotective metal-organic frameworks for anaerobic bacteria.
AB  - We report a strategy to uniformly wrap Morella thermoacetica bacteria with a
      metal-organic framework (MOF) monolayer of nanometer thickness for cytoprotection
      in artificial photosynthesis. The catalytic activity of the MOF enclosure toward
      decomposition of reactive oxygen species (ROS) reduces the death of strictly
      anaerobic bacteria by fivefold in the presence of 21% O2, and enables the
      cytoprotected bacteria to continuously produce acetate from CO2 fixation under
      oxidative stress. The high definition of the MOF-bacteria interface involving
      direct bonding between phosphate units on the cell surface and zirconium clusters
      on MOF monolayer, provides for enhancement of life throughout reproduction. The
      dynamic nature of the MOF wrapping allows for cell elongation and separation,
      including spontaneous covering of the newly grown cell surface. The open-metal
      sites on the zirconium clusters lead to 600 times more efficient ROS
      decomposition compared with zirconia nanoparticles.

PMID- 30275327
TI  - HEIP1 regulates crossover formation during meiosis in rice.
AB  - During meiosis, the number of double-strand breaks (DSBs) far exceeds the final
      number of crossovers (COs). Therefore, to identify proteins involved in
      determining which of these DSBs repaired into COs is critical in understanding
      the mechanism of CO control. Across species, HEI10-related proteins play
      important roles in CO formation. Here, through screening for HEI10-interacting
      proteins via a yeast two-hybrid system, we identify a CO protein HEI10
      Interaction Protein 1 (HEIP1) in rice. HEIP1 colocalizes with HEI10 in a dynamic
      fashion along the meiotic chromosomes and specially localizes onto crossover
      sites from late pachytene to diplotene. Between these two proteins, HEI10 is
      required for the loading of HEIP1, but not vice versa. Moreover, mutations of the
      HEIP1 gene cause the severe reduction of chiasma frequency, whereas early
      homologous recombination processes are not disturbed and synapsis proceeds
      normally. HEIP1 interacts directly with ZIP4 and MSH5. In addition, the loading
      of HEIP1 depends on ZIP4, but not on MER3, MSH4, or MSH5. Together, our results
      suggest that HEIP1 may be a member of the ZMM group and acts as a key element
      regulating CO formation.

PMID- 30275328
TI  - Viable cyanobacteria in the deep continental subsurface.
AB  - Cyanobacteria are ecologically versatile microorganisms inhabiting most
      environments, ranging from marine systems to arid deserts. Although they possess
      several pathways for light-independent energy generation, until now their
      ecological range appeared to be restricted to environments with at least
      occasional exposure to sunlight. Here we present molecular, microscopic, and
      metagenomic evidence that cyanobacteria predominate in deep subsurface rock
      samples from the Iberian Pyrite Belt Mars analog (southwestern Spain).
      Metagenomics showed the potential for a hydrogen-based lithoautotrophic
      cyanobacterial metabolism. Collectively, our results suggest that they may play
      an important role as primary producers within the deep-Earth biosphere. Our
      description of this previously unknown ecological niche for cyanobacteria paves
      the way for models on their origin and evolution, as well as on their potential
      presence in current or primitive biospheres in other planetary bodies, and on the
      extant, primitive, and putative extraterrestrial biospheres.

PMID- 30275329
TI  - Proinsulin C-peptide is an autoantigen in people with type 1 diabetes.
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta
      cells, found within the islets of Langerhans in the pancreas, are destroyed by
      islet-infiltrating T cells. Identifying the antigenic targets of beta-cell
      reactive T cells is critical to gain insight into the pathogenesis of T1D and
      develop antigen-specific immunotherapies. Several lines of evidence indicate that
      insulin is an important target of T cells in T1D. Because many human islet
      infiltrating CD4+ T cells recognize C-peptide-derived epitopes, we hypothesized
      that full-length C-peptide (PI33-63), the peptide excised from proinsulin as it
      is converted to insulin, is a target of CD4+ T cells in people with T1D. CD4+ T
      cell responses to full-length C-peptide were detected in the blood of: 14 of 23
      (>60%) people with recent-onset T1D, 2 of 15 (>13%) people with long-standing
      T1D, and 1 of 13 (<8%) HLA-matched people without T1D. C-peptide-specific CD4+ T
      cell clones, isolated from six people with T1D, recognized epitopes from the
      entire 31 amino acids of C-peptide. Eighty-six percent (19 of 22) of the C
      peptide-specific clones were restricted by HLA-DQ8, HLA-DQ2, HLA-DQ8trans, or HLA
      DQ2trans, HLA alleles strongly associated with risk of T1D. We also found that
      full-length C-peptide was a much more potent agonist of some CD4+ T cell clones
      than an 18mer peptide encompassing the cognate epitope. Collectively, our
      findings indicate that proinsulin C-peptide is a key target of autoreactive CD4+
      T cells in T1D. Hence, full-length C-peptide is a promising candidate for antigen
      specific immunotherapy in T1D.

PMID- 30275330
TI  - Allosteric potentiation of a ligand-gated ion channel is mediated by access to a
      deep membrane-facing cavity.
AB  - Theories of general anesthesia have shifted in focus from bulk lipid effects to
      specific interactions with membrane proteins. Target receptors include several
      subtypes of pentameric ligand-gated ion channels; however, structures of
      physiologically relevant proteins in this family have yet to define anesthetic
      binding at high resolution. Recent cocrystal structures of the bacterial protein
      GLIC provide snapshots of state-dependent binding sites for the common surgical
      agent propofol (PFL), offering a detailed model system for anesthetic modulation.
      Here, we combine molecular dynamics and oocyte electrophysiology to reveal
      differential motion and modulation upon modification of a transmembrane binding
      site within each GLIC subunit. WT channels exhibited net inhibition by PFL, and a
      contraction of the cavity away from the pore-lining M2 helix in the absence of
      drug. Conversely, in GLIC variants exhibiting net PFL potentiation, the cavity
      was persistently expanded and proximal to M2. Mutations designed to favor this
      deepened site enabled sensitivity even to subclinical concentrations of PFL, and
      a uniquely prolonged mode of potentiation evident up to ~30 min after washout.
      Dependence of these prolonged effects on exposure time implicated the membrane as
      a reservoir for a lipid-accessible binding site. However, at the highest measured
      concentrations, potentiation appeared to be masked by an acute inhibitory effect,
      consistent with the presence of a discrete, water-accessible site of inhibition.
      These results support a multisite model of transmembrane allosteric modulation,
      including a possible link between lipid- and receptor-based theories that could
      inform the development of new anesthetics.

PMID- 30275331
TI  - Adult spinal motoneurons change their neurotransmitter phenotype to control
      locomotion.
AB  - A particularly essential determinant of a neuron's functionality is its
      neurotransmitter phenotype. While the prevailing view is that neurotransmitter
      phenotypes are fixed and determined early during development, a growing body of
      evidence suggests that neurons retain the ability to switch between different
      neurotransmitters. However, such changes are considered unlikely in motoneurons
      due to their crucial functional role in animals' behavior. Here we describe the
      expression and dynamics of glutamatergic neurotransmission in the adult zebrafish
      spinal motoneuron circuit assembly. We demonstrate that part of the fast
      motoneurons retain the ability to switch their neurotransmitter phenotype under
      physiological (exercise/training) and pathophysiological (spinal cord injury)
      conditions to corelease glutamate in the neuromuscular junctions to enhance
      animals' motor output. Our findings suggest that motoneuron neurotransmitter
      switching is an important plasticity-bestowing mechanism in the reconfiguration
      of spinal circuits that control movements.

PMID- 30275332
TI  - Membrane tethering by the autophagy ATG2A-WIPI4 complex.

PMID- 30275333
TI  - Parcellating the structure and function of the reading circuit.

PMID- 30275334
TI  - Rapid diversification of Pseudomonas aeruginosa in cystic fibrosis lung-like
      conditions.
AB  - Chronic infection of the cystic fibrosis (CF) airway by the opportunistic
      pathogen Pseudomonas aeruginosa is the leading cause of morbidity and mortality
      for adult CF patients. Prolonged infections are accompanied by adaptation of P.
      aeruginosa to the unique conditions of the CF lung environment, as well as marked
      diversification of the pathogen into phenotypically and genetically distinct
      strains that can coexist for years within a patient. Little is known, however,
      about the causes of this diversification and its impact on patient health. Here,
      we show experimentally that, consistent with ecological theory of
      diversification, the nutritional conditions of the CF airway can cause rapid and
      extensive diversification of P. aeruginosa Mucin, the substance responsible for
      the increased viscosity associated with the thick mucus layer in the CF airway,
      had little impact on within-population diversification but did promote divergence
      among populations. Furthermore, in vitro evolution recapitulated traits thought
      to be hallmarks of chronic infection, including reduced motility and increased
      biofilm formation, and the range of phenotypes observed in a collection of
      clinical isolates. Our results suggest that nutritional complexity and reduced
      dispersal can drive evolutionary diversification of P. aeruginosa independent of
      other features of the CF lung such as an active immune system or the presence of
      competing microbial species. We suggest that diversification, by generating
      extensive phenotypic and genetic variation on which selection can act, may be a
      key first step in the development of chronic infections.

PMID- 30275335
TI  - Coordination of cell migration mediated by site-dependent cell-cell contact.
AB  - Contact inhibition of locomotion (CIL), the repulsive response of cells upon cell
      cell contact, has been the predominant paradigm for contact-mediated responses.
      However, it is difficult for CIL alone to account for the complex behavior of
      cells within a multicellular environment, where cells often migrate in cohorts
      such as sheets, clusters, and streams. Although cell-cell adhesion and mechanical
      interactions play a role, how individual cells coordinate their migration within
      a multicellular environment remains unclear. Using micropatterned substrates to
      guide cell migration and manipulate cell-cell contact, we show that contacts
      between different regions of cells elicit different responses. Repulsive
      responses were limited to interaction with the head of a migrating cell, while
      contact with the tail of a neighboring cell promoted migration toward the tail.
      The latter behavior, termed contact following of locomotion (CFL), required the
      Wnt signaling pathway. Inhibition of the Wnt pathway disrupted not only CFL but
      also collective migration of epithelial cells, without affecting the migration of
      individual cells. In contrast, inhibition of myosin II with blebbistatin
      disrupted the migration of both individual epithelial cells and collectives. We
      propose that CFL, in conjunction with CIL, plays a major role in guiding and
      coordinating cell migration within a multicellular environment.

PMID- 30275339
TI  - What Is Most Important in Rheumatoid Arthritis Treatment - Where You Are, Who You
      Are, or Where You Are Going?

PMID- 30275337
TI  - Serotonin signaling regulates insulin-like peptides for growth, reproduction, and
      metabolism in the disease vector Aedes aegypti.
AB  - Disease-transmitting female mosquitoes require a vertebrate blood meal to produce
      their eggs. An obligatory hematophagous lifestyle, rapid reproduction, and
      existence of a large number of transmittable diseases make mosquitoes the world's
      deadliest animals. Attaining optimal body size and nutritional status is critical
      for mosquitoes to become reproductively competent and effective disease vectors.
      We report that blood feeding boosts serotonin concentration and elevates the
      serotonin receptor Aa5HT2B (Aedes aegypti 5-hydroxytryptamine receptor, type 2B)
      transcript level in the fat-body, an insect analog of the vertebrate liver and
      adipose tissue. Aa5HT2B gene disruption using the CRISPR-Cas9 gene-editing
      approach led to a decreased body size, postponed development, shortened lifespan,
      retarded ovarian growth, and dramatically diminished lipid accumulation.
      Expression of the insulin-like peptide (ILP) genes ilp2 and ilp6 was down
      regulated while that of ilp5 and ilp4 was up-regulated in response to Aa5HT2B
      disruption. CRISPR-Cas9 disruption of ilp2 or ilp6 resulted in adverse phenotypes
      similar to those of Aa5HT2B disruption, while ilp5 CRISPR-Cas9 disruption had
      exactly the opposite effect on growth and metabolism, with significantly
      increased body size and elevated lipid stores. Simultaneous CRISPR-Cas9
      disruption of Aa5HT2B and ilp5 rescued these phenotypic manifestations. Aa5HT2B
      RNAi silencing rendered ilp6 insensitive to serotonin treatment in the cultured
      fat-body, suggesting a regulatory link between Aa5HT2B and ILP6. Moreover, CRISPR
      Cas9 ilp6 disruption affects expression of ilp-2, -5, and -4, pointing out on a
      possible role of ILP6 as a mediator of the Aa5HT2B action.

PMID- 30275338
TI  - Active apolar doping determines routes to colloidal clusters and gels.
AB  - Collections of interacting active particles, self-propelling or not, have shown
      remarkable phenomena including the emergence of dynamic patterns across different
      length scales, from animal groups to vibrated grains, microtubules, bacteria, and
      chemical- or field-driven colloids. Burgeoning experimental and simulation
      activities are now exploring the possibility of realizing solid and stable
      structures from passive elements that are assembled by a few active dopants. Here
      we show that such an elusive task may be accomplished by using a small amount of
      apolar dopants, namely synthetic active but not self-propelling units. We use
      blue light to rapidly assemble 2D colloidal clusters and gels via nonequilibrium
      diffusiophoresis, where microscopic hematite dockers form long-living
      interstitial bonds that strongly glue passive silica microspheres. By varying the
      relative fraction of doping, we uncover a rich phase diagram including ordered
      and disordered clusters, space-filling gels, and bicontinuous structures formed
      by filamentary dockers percolating through a solid network of silica spheres. We
      characterize the slow relaxation and dynamic arrest of the different phases via
      correlation and scattering functions. Our findings provide a pathway toward the
      rapid engineering of mesoscopic gels and clusters via active colloidal doping.

PMID- 30275340
TI  - Crowned Dens Syndrome: Calcium Pyrophosphate Deposition Disease Masquerading as
      Osteomyelitis.

PMID- 30275336
TI  - High-throughput in vivo screen of functional mRNA delivery identifies
      nanoparticles for endothelial cell gene editing.
AB  - Dysfunctional endothelium causes more disease than any other cell type.
      Systemically administered RNA delivery to nonliver tissues remains challenging,
      in large part because there is no high-throughput method to identify
      nanoparticles that deliver functional mRNA to cells in vivo. Here we report a
      system capable of simultaneously quantifying how >100 lipid nanoparticles (LNPs)
      deliver mRNA that is translated into functional protein. Using this system (named
      FIND), we measured how >250 LNPs delivered mRNA to multiple cell types in vivo
      and identified 7C2 and 7C3, two LNPs that efficiently deliver siRNA, single-guide
      RNA (sgRNA), and mRNA to endothelial cells. The 7C3 delivered Cas9 mRNA and sgRNA
      to splenic endothelial cells as efficiently as hepatocytes, distinguishing it
      from LNPs that deliver Cas9 mRNA and sgRNA to hepatocytes more than other cell
      types. These data demonstrate that FIND can identify nanoparticles with novel
      tropisms in vivo.

PMID- 30275341
TI  - Retro-odontoid Pseudotumor Associated with Sjogren Syndrome and Systemic Lupus
      Erythematosus Serology.

PMID- 30275342
TI  - Chikungunya in Brazil: Rheumatologists on the Front Line.

PMID- 30275343
TI  - New Player in Endosomal Trafficking: Differential Roles of Smad Anchor for
      Receptor Activation (SARA) Protein.
AB  - The development and maintenance of multicellular organisms require specialized
      coordination between external cellular signals and the proteins receiving stimuli
      and regulating responses. A critical role in the proper functioning of these
      processes is played by endosomal trafficking, which enables the transport of
      proteins to targeted sites as well as their return to the plasma membrane through
      its essential components, the endosomes. During this trafficking, signaling
      pathways controlling functions related to the endosomal system are activated both
      directly and indirectly. Although there are a considerable number of molecules
      participating in these processes, some are more known than others for their
      specific functions. Toward the end of the 1990s, Smad anchor for receptor
      activation (SARA) protein was described to be controlling and to facilitate the
      localization of Smads to transforming growth factor beta (TGF-beta) receptors
      during TGF-beta signaling activation, and, strikingly, SARA was also identified
      to be one of the proteins that bind to early endosomes (EEs) participating in
      membrane trafficking in several cell models. The purpose of this review is to
      analyze the state of the art of the contribution of SARA in different cell types
      and cellular contexts, focusing on the biological role of SARA in two main
      processes, trafficking and cellular signaling, both of which are necessary for
      intercellular coordination, communication, and development.

PMID- 30275344
TI  - Mediator Is Essential for Small Nuclear and Nucleolar RNA Transcription in Yeast.
AB  - Eukaryotic RNA polymerase II (RNAPII) transcribes mRNA genes and non-protein
      coding RNA (ncRNA) genes, including those encoding small nuclear and nucleolar
      RNAs (sn/snoRNAs). In metazoans, RNAPII transcription of sn/snoRNAs is
      facilitated by a number of specialized complexes, but no such complexes have been
      discovered in yeast. It has been proposed that yeast sn/snoRNA and mRNA
      expression relies on a set of common factors, but the extent to which regulators
      of mRNA genes function at yeast sn/snoRNA genes is unclear. Here, we investigated
      a potential role for the Mediator complex, essential for mRNA gene transcription,
      in sn/snoRNA gene transcription. We found that Mediator maps to sn/snoRNA gene
      regulatory regions and that rapid depletion of the essential structural subunit
      Med14 strongly reduces RNAPII and TFIIB occupancy as well as nascent
      transcription of sn/snoRNA genes. Deletion of Med3 and Med15, subunits of the
      activator-interacting Mediator tail module, does not affect Mediator recruitment
      to or RNAPII and TFIIB occupancy of sn/snoRNA genes. Our analyses suggest that
      Mediator promotes PIC formation and transcription at sn/snoRNA genes, expanding
      the role of this critical regulator beyond its known functions in mRNA gene
      transcription and demonstrating further mechanistic similarity between the
      transcription of mRNA and sn/snoRNA genes.

PMID- 30275346
TI  - Haemogregarine (Apicomplexa: Adeleorina) infection in Vanderhaege's toad-headed
      turtle, Mesoclemmys vanderhaegei (Chelidae), from a Brazilian Neotropical savanna
      region.
AB  - Knowledge of blood parasites in Brazilian chelonians is limited, since they have
      been recorded in only six species. Mesoclemmys vanderhaegei (Bour) is a
      freshwater turtle with a wide geographic distribution in Brazil, but there is
      little information about its natural history. This paper reports on a study of
      the prevalence and infection intensity of a haemogregarine in two subpopulations
      of M. vanderhaegei. The study was conducted in two areas of Cerrado in the Upper
      Paraguay River basin in the state of Mato Grosso, Brazil, between November 2010
      and August 2013. Ninety-five (53%) of the 179 turtles captured were positive for
      haemogregarine parasites. The parasitic forms observed were two morphotypes of
      intraerythrocytic gametocytes. The prevalence differed between size classes,
      increasing significantly according to the animals' body size. There was no
      significant difference between prevalence and sex, or between sampling periods.
      The mean parasite intensity was 9 parasites/2,000 erythrocytes (0.45%) and the
      parasite population presented an aggregated distribution, with an aggregation
      index of 19 and discrepancy of 0.772. This is the first record of a hemoparasite
      in the freshwater turtle M. vanderhaegei.

PMID- 30275345
TI  - Hsp70 Interacts with Mitogen-Activated Protein Kinase (MAPK)-Activated Protein
      Kinase 2 To Regulate p38MAPK Stability and Myoblast Differentiation during
      Skeletal Muscle Regeneration.
AB  - The regenerative process of injured muscle is dependent on the fusion and
      differentiation of myoblasts derived from muscle stem cells. Hsp70 is important
      for maintaining skeletal muscle homeostasis and regeneration, but the precise
      cellular mechanism remains elusive. In this study, we found that Hsp70 was
      upregulated during myoblast differentiation. Depletion or inhibition of
      Hsp70/Hsc70 impaired myoblast differentiation. Importantly, overexpression of p38
      mitogen-activated protein kinase alpha (p38MAPKalpha) but not AKT1 rescued the
      impairment of myogenic differentiation in Hsp70- or Hsc70-depleted myoblasts.
      Moreover, Hsp70 interacted with MK2, a substrate of p38MAPK, to regulate the
      stability of p38MAPK. Knockdown of Hsp70 also led to downregulation of both MK2
      and p38MAPK in intact muscles and during cardiotoxin-induced muscle regeneration.
      Hsp70 bound MK2 to regulate MK2-p38MAPK interaction in myoblasts. We subsequently
      identified the essential regions required for Hsp70-MK2 interaction. Functional
      analyses showed that MK2 is essential for both myoblast differentiation and
      skeletal muscle regeneration. Taken together, our findings reveal a novel role of
      Hsp70 in regulating myoblast differentiation by interacting with MK2 to stabilize
      p38MAPK.

PMID- 30275347
TI  - Enhanced Upconversion and Downshifting emissions from Tb3+, Yb3+ co-doped CaZrO3
      phosphor in presence of Li+ ions.
AB  - This paper reports the enhanced green photoluminescence from Tb3+, Yb3+ co-doped
      CaZrO3 phosphor in the presence of Li+ ion synthesized through solid state
      reaction technique. The structural studies show an increase in the particle size
      and a shrink in crystal lattice due to Li+ co-doping in the phosphor. The
      phosphor sample emits intense green upconversion emission (UC) due to Tb3+ ions
      on excitation with 980 nm radiation which is further enhanced ~ 28 times on Li+
      co-doping. The lifetime of 5D4 level of Tb3+ ion decreases in the presence of Li+
      ions due to increase in asymmetry in crystal field. The downshifting (DS)
      emission intensity monitored on 378 and 487nm excitations is also enhanced in the
      presence of Li+ ions. Thus, the Tb3+, Yb3+, Li+ co-doped CaZrO3 phosphor can be a
      suitable candidate for UC solid state lighting.

PMID- 30275348
TI  - Anodic Stimulation Misunderstood: Preferential Activation of Fiber Orientations
      with Anodic Waveforms in Deep Brain Stimulation.
AB  - OBJECTIVE:  During deep brain stimulation (DBS), it is well understood that
      extracellular cathodic stimulation can cause activation of passing axons.
      Activation can be predicted from the second derivative of the electric potential
      along an axon, which depends on axonal orientation with respect to the
      stimulation source. We hypothesize that fiber orientation influences activation
      thresholds and that fiber orientations can be selectively targeted with DBS
      waveforms.&#13; &#13; Approach: We used bioelectric field and multicompartment
      NEURON models to explore preferential activation based on fiber orientation
      during monopolar or bipolar stimulation. Preferential fiber orientation was
      extracted from the principal eigenvectors and eigenvalues of the Hessian matrix
      of the electric potential. We tested cathodic, anodic, and charge-balanced pulses
      to target neurons based on fiber orientation in general and clinical
      scenarios.&#13; &#13; Main Results: Axons passing the DBS lead have positive
      second derivatives around a cathode, whereas orthogonal axons have positive
      second derivatives around an anode, as indicated by the Hessian. Multicompartment
      NEURON models confirm that passing fibers are activated by cathodic stimulation,
      and orthogonal fibers are activated by anodic stimulation. Additionally,
      orthogonal axons have lower thresholds compared to passing axons. In a clinical
      scenario, fiber pathways associated with therapeutic benefit can be targeted with
      anodic stimulation at 50% lower stimulation amplitudes.&#13; &#13; Significance:
      Fiber orientations can be selectively targeted with simple changes to the
      stimulus waveform. Anodic stimulation preferentially activates orthogonal fibers,
      approaching or leaving the electrode, at lower thresholds for similar therapeutic
      benefit in DBS with decreased power consumption.

PMID- 30275349
TI  - Combination Therapy for Reconstructive Periodontal Treatment in the Lower
      Anterior Area: Clinical Evaluation of a Case Series.
AB  - Clinically, periodontal regeneration may be achieved by the application of
      barrier membranes, grafts, wound-healing modifiers, and their combinations.
      Combination therapy refers to the simultaneous application of various periodontal
      reconstructive treatment alternatives to obtain additive effects. This approach
      may lead to assemblage of different regenerative principles, such as conductivity
      and inductivity, space provision and wound stability, matrix development and cell
      differentiation. The application of autogenous connective tissue grafts during
      periodontal regenerative treatment with enamel matrix proteins derivative (EMD)
      has been previously reported. The present case series present a modified approach
      for treatment of severe periodontally involved lower incisors presenting with
      thin gingival biotype, gingival recession, minimal attached and keratinized
      gingiva width and muscle and/or frenum pull. In all cases a combination therapy
      consisting of a single buccal access flap, root conditioning, EMD application on
      the denuded root surfaces and a free connective tissue graft was performed.
      Clinical and radiographic outcomes were consistently satisfactory, leading to
      probing depth reduction, clinical attachment gain, minimal gingival recession,
      increased attached and keratinizing gingival width, elimination of frenum and/or
      muscle pull together with radiographic bone fill of the defects. It may be
      concluded that the present combination therapy for reconstructive periodontal
      treatment in the lower anterior area is a valuable alternative for indicated
      cases.

PMID- 30275351
TI  - High Temperature Deformation Behavior of In-Situ Synthesized Titanium-Based
      Composite Reinforced with Ultra-Fine TiB Whiskers.
AB  - A TiB/Ti-6Al-4V composite reinforced with ultra-fine TiB whiskers (UF-TiB) was
      prepared by the powder metallurgy method. High temperature compression tests were
      carried out to study the hot deformation behavior of the UF-TiB/Ti-6Al-4V
      composite. The compressive deformation was performed in the temperature range of
      900-1200  degrees C and the strain rate range of 0.001-10 s-1. The results showed
      that stable flow occurred at the condition of 900-1200  degrees C/0.001-0.01 s-1.
      The optimum working condition was 900  degrees C/0.001 s-1, with the deformation
      mechanism of dynamic recrystallization (DRX). Instable flow occurred when the
      strain rate was higher than 0.01 s-1, where the failure modes included adiabatic
      shear deformation, whisker breakage and whisker/matrix debonding. The
      deformability of the UF-TiB/Ti-6Al-4V composite was much better than the
      traditional casted and the pressed + sintered TiB/Ti-6Al-4V composites, which are
      typically reinforced with coarse-grained TiB whiskers. The high deformability was
      primarily attributed to the ultra-fine reinforcements, which could coordinate the
      deformation more effectively. In addition, a fine matrix microstructure also had
      a positive effect on deformability because the fine matrix microstructure could
      improve the grain boundary sliding.

PMID- 30275352
TI  - Fabrication of Micro-Parts with High-Aspect Ratio Micro-Hole Array by Micro
      Powder Injection Molding.
AB  - The present study investigated high-aspect ratio micro-hole array parts which
      were made by ZrO2 micro-powder with different particle sizes and micro-powder
      injection molding technology. It analysed the influence of particle sizes on
      feedstock, debinding and sintering of ceramic nozzles with multi-micro-holes. The
      forming quality of ceramic nozzles with multi-micro-holes was discussed in this
      paper. The results show that the two mixed ZrO2 feedstocks have fine uniformity.
      The average deviation of the feedstock made with 200 nm powder was -2%, and the
      average deviation of the feedstock made with 100 nm powder was -7.1%. The sample
      showed certain sintering characteristics which provided better strength (11.10
      MPa) to parts after debinding. The linear shrinkage and the density of the two
      powder samples at different sintering temperatures increased as the sintering
      temperature increased. If the temperature continued to increase, the linear
      shrinkage and the density decreased. The highest hardness and flexural strength
      values of the ZrO2 sample with 200 nm powder used were: 1265.5 HV and 453.4 MPa,
      and the crystalline particle size was 0.36 MUm. The highest hardness and flexural
      strength values of the ZrO2 sample with 100 nm powder used were: 1425.8 HV and
      503.6 MPa, and the crystalline particle size was 0.18 MUm. The ceramic nozzles
      with multi-micro holes shrunk to nearly the same axial, radial and
      circumferential directions during sintering. After sintering, the roundness of
      ceramic micro-hole met the user requirements, and the circular hole had a high
      parallelism in the axial direction. The micropore diameter was 450 +/- 5 MUm, and
      it was possible to control the dimensional accuracy within 1.5% after sintering.
      The study presented a superior application prospect for high-aspect ratio micro
      hole array parts in aerospace, electronics and biomedicine.

PMID- 30275350
TI  - The Consumption of Beef Burgers Prepared with Wine Grape Pomace Flour Improves
      Fasting Glucose, Plasma Antioxidant Levels, and Oxidative Damage Markers in
      Humans: A Controlled Trial.
AB  - Wine grape pomace flour (WGPF) is a fruit byproduct that is high in fiber and
      antioxidants. We tested whether WGPF consumption could affect blood biochemical
      parameters, including oxidative stress biomarkers. In a three-month intervention
      study, 27 male volunteers, each with some components of metabolic syndrome,
      consumed a beef burger supplemented with 7% WGPF containing 3.5% of fiber and 1.2
      mg gallic equivalents (GE)/g of polyphenols (WGPF-burger), daily, during the
      first month. The volunteers consumed no burgers in the second month, and one
      control-burger daily in the third month. At baseline and after these periods, we
      evaluated the metabolic syndrome components, plasma antioxidant status (i.e., 2,2
      diphenyl-1-picrylhydrazyl radical scavenging capacity (DPPH), vitamin E, vitamin
      C), and oxidative damage markers (i.e., advanced oxidation protein products
      (AOPPs), oxidized low-density lipoproteins (oxLDLs), malondialdehyde (MDA)). The
      WGPF-burger intake significantly reduced glycemia and homeostatic model
      assessment-based measurement of insulin resistance. Vitamin C increased and
      decreased during the consumption of the WGPF-burger and control-burger,
      respectively. The WGPF-burger intake significantly decreased AOPP and oxLDL
      levels. Vitamin E and MDA levels showed no significant changes. In conclusion,
      the consumption of beef burgers prepared with WGPF improved fasting glucose and
      insulin resistance, plasma antioxidant levels, and oxidative damage markers.
      Therefore, this functional ingredient has potential as a dietary supplement to
      manage chronic disease risk in humans.

PMID- 30275353
TI  - Chrysoxanthones A-C, Three New Xanthone-Chromanone Heterdimers from Sponge
      Associated Penicillium chrysogenum HLS111 Treated with Histone Deacetylase
      Inhibitor.
AB  - By treating with histone-deacetylase inhibitor valproate sodium, three new
      heterdimeric tetrahydroxanthone-chromanone lactones chrysoxanthones A-C (1-3),
      along with 17 known compounds were isolated from a sponge-associated Penicillium
      chrysogenum HLS111. The planar structures of chrysoxanthones A-C were elucidated
      by means of spectroscopic analyses, including MS, 1D, and 2D NMR. Their absolute
      configurations were established by electronic circular dichroism (ECD)
      calculations. Chrysoxanthones A-C exhibited moderate antibacterial activities
      against Bacillus subtilis with minimum inhibitory concentration (MIC) values of 5
      10 MUg/mL.

PMID- 30275355
TI  - A Novel Cold-Adapted Leucine Dehydrogenase from Antarctic Sea-Ice Bacterium
      Pseudoalteromonas sp. ANT178.
AB  - l-tert-leucine and its derivatives are useful as pharmaceutical active
      ingredients, in which leucine dehydrogenase (LeuDH) is the key enzyme in their
      enzymatic conversions. In the present study, a novel cold-adapted LeuDH, psleudh,
      was cloned from psychrotrophic bacteria Pseudoalteromonas sp. ANT178, which was
      isolated from Antarctic sea-ice. Bioinformatics analysis of the gene psleudh
      showed that the gene was 1209 bp in length and coded for a 42.6 kDa protein
      containing 402 amino acids. PsLeuDH had conserved Phe binding site and NAD+
      binding site, and belonged to a member of the Glu/Leu/Phe/Val dehydrogenase
      family. Homology modeling analysis results suggested that PsLeuDH exhibited more
      glycine residues, reduced proline residues, and arginine residues, which might be
      responsible for its catalytic efficiency at low temperature. The recombinant
      PsLeuDH (rPsLeuDH) was purified a major band with the high specific activity of
      275.13 U/mg using a Ni-NTA affinity chromatography. The optimum temperature and
      pH for rPsLeuDH activity were 30  degrees C and pH 9.0, respectively.
      Importantly, rPsLeuDH retained at least 40% of its maximum activity even at 0 
      degrees C. Moreover, the activity of rPsLeuDH was the highest in the presence of
      2.0 M NaCl. Substrate specificity and kinetic studies of rPsLeuDH demonstrated
      that l-leucine was the most suitable substrate, and the catalytic activity at low
      temperatures was ensured by maintaining a high kcat value. The results of the
      current study would provide insight into Antarctic sea-ice bacterium LeuDH, and
      the unique properties of rPsLeuDH make it a promising candidate as a biocatalyst
      in medical and pharmaceutical industries.

PMID- 30275354
TI  - Novel Gel Formulations as Topical Carriers for the Essential Oil of Bidens
      tripartita for the Treatment of Candidiasis.
AB  - The genus Bidens L. (Asteraceae) refers to several species of plants used in
      traditional phytotherapeutic preparations. B. tripartita, also known as bur
      marigold, is the most familiar plant and has been known as a remedy for chronic
      dysentery. The hydrodistilled essential oil of the aerial parts of the Polish B.
      tripartita was analyzed using gas chromatography (GC) and gas chromatography-mass
      spectrometry (GC-MS) techniques. To exclude any potential toxic effects of the
      oil on human dermal fibroblasts, the MTT test (methyl thiazolyl tetrazolium) and
      COMET assay (single-cell gel electrophoresis) were performed. Novel gel
      formulations as topical carriers for essential oil obtained from B. tripartita
      were developed and characterized. The bioadhesive properties of the designed
      preparations in the ex vivo model using the skin of hairless mice were also
      evaluated. The therapeutic efficacy of the topical formulations is influenced by
      active phytoconstituents and vehicle characteristics. The antifungal properties
      of the essential oil of B. tripartita were also tested against Candida species,
      and this oil appears to be a promising topical anticandidal agent.

PMID- 30275357
TI  - Molecular Lesions of Insulator CTCF and Its Paralogue CTCFL (BORIS) in Cancer: An
      Analysis from Published Genomic Studies.
AB  - CTCF (CCCTC-binding factor) is a transcription regulator with hundreds of binding
      sites in the human genome. It has a main function as an insulator protein,
      defining together with cohesins the boundaries of areas of the genome called
      topologically associating domains (TADs). TADs contain regulatory elements such
      as enhancers which function as regulators of the transcription of genes inside
      the boundaries of the TAD while they are restricted from regulating genes outside
      these boundaries. This paper will examine the most common genetic lesions of CTCF
      as well as its related protein CTCFL (CTCF-like also called BORIS) in cancer
      using publicly available data from published genomic studies. Cancer types where
      abnormalities in the two genes are more common will be examined for possible
      associations with underlying repair defects or other prevalent genetic lesions.
      The putative functional effects in CTCF and CTCFL lesions will also be explored.

PMID- 30275356
TI  - Effect of Branched-Chain Amino Acid Supplementation on Recovery Following Acute
      Eccentric Exercise.
AB  - This study investigated the effect of branched-chain amino acid (BCAA)
      supplementation on recovery from eccentric exercise. Twenty males ingested either
      a BCAA supplement or placebo (PLCB) prior to and following eccentric exercise.
      Creatine kinase (CK), vertical jump (VJ), maximal voluntary isometric contraction
      (MVIC), jump squat (JS) and perceived soreness were assessed. No significant (p >
      0.05) group by time interaction effects were observed for CK, soreness, MVIC, VJ,
      or JS. CK concentrations were elevated above baseline (p < 0.001) in both groups
      at 4, 24, 48 and 72 hr, while CK was lower (p = 0.02) in the BCAA group at 48 hr
      compared to PLCB. Soreness increased significantly from baseline (p < 0.01) in
      both groups at all time-points; however, BCAA supplemented individuals reported
      less soreness (p < 0.01) at the 48 and 72 hr time-points. MVIC force output
      returned to baseline levels (p > 0.05) at 24, 48 and 72 hr for BCAA individuals.
      No significant difference between groups (p > 0.05) was detected for VJ or JS.
      BCAA supplementation may mitigate muscle soreness following muscle-damaging
      exercise. However, when consumed with a diet consisting of ~1.2 g/kg/day protein,
      the attenuation of muscular performance decrements or corresponding plasma CK
      levels are likely negligible.

PMID- 30275358
TI  - Detailed Modeling of the Direct Reduction of Iron Ore in a Shaft Furnace.
AB  - This paper addresses the modeling of the iron ore direct reduction process, a
      process likely to reduce CO2 emissions from the steel industry. The shaft furnace
      is divided into three sections (reduction, transition, and cooling), and the
      model is two-dimensional (cylindrical geometry for the upper sections and conical
      geometry for the lower one), to correctly describe the lateral gas feed and
      cooling gas outlet. This model relies on a detailed description of the main
      physical-chemical and thermal phenomena, using a multi-scale approach. The moving
      bed is assumed to be comprised of pellets of grains and crystallites. We also
      take into account eight heterogeneous and two homogeneous chemical reactions. The
      local mass, energy, and momentum balances are numerically solved, using the
      finite volume method. This model was successfully validated by simulating the
      shaft furnaces of two direct reduction plants of different capacities. The
      calculated results reveal the detailed interior behavior of the shaft furnace
      operation. Eight different zones can be distinguished, according to their
      predominant thermal and reaction characteristics. An important finding is the
      presence of a central zone of lesser temperature and conversion.

PMID- 30275360
TI  - A Customer Feedback Platform for Vehicle Manufacturing Compliant with Industry
      4.0 Vision.
AB  - In the last decade, the growth of the automotive market with the aid of
      technologies has been notable for the economic, automotive and technological
      sectors. Alongside this growing recognition, the so called Internet of
      Intelligent Vehicles (IoIV) emerges as an evolution of the Internet of Things
      (IoT) applied to the automotive sector. Closely related to IoIV, emerges the
      concept of Industrial Internet of Things (IIoT), which is the current revolution
      seen in industrial automation. IIoT, in its turn, relates to the concept of
      Industry 4.0, that is used to represent the current Industrial Revolution. This
      revolution, however, involves different areas: from manufacturing to healthcare.
      The Industry 4.0 can create value during the entire product lifecycle, promoting
      customer feedback, that is, having information about the product history
      throughout it is life. In this way, the automatic communication between vehicle
      and factory was facilitated, allowing the accomplishment of different analysis
      regarding vehicles, such as the identification of a behavioral pattern through
      historical driver usage, fuel consumption, maintenance indicators, so on. Thus,
      allowing the prevention of critical issues and undesired behaviors, since the
      automakers lose contact with the vehicle after the purchase. Therefore, this
      paper aims to propose a customer feedback platform for vehicle manufacturing in
      Industry 4.0 context, capable of collecting and analyzing, through an OBD-II (On
      Board Diagnostics) scanner, the sensors available by vehicles, with the purpose
      of assisting in the management, prevention, and mitigation of different vehicular
      problems. An intercontinental evaluation conducted between Brazil and Italy
      locations shown the feasibility of platform and the potential to use in order to
      improve the vehicle manufacturing process.

PMID- 30275359
TI  - The Role of Physical Stimuli on Calcium Channels in Chondrogenic Differentiation
      of Mesenchymal Stem Cells.
AB  - Human mesenchymal stem cells (hMSC) are becoming increasingly popular in tissue
      engineering. They are the most frequently used stem cell source for clinical
      applications due to their high potential to differentiate into several lineages.
      Cartilage is known for its low capacity for self-maintenance and currently there
      are no efficient methods to improve cartilage repair. Chondrogenic
      differentiation of hMSC isolated from different tissues is widely employed due to
      a high clinical demand for the improvement of cartilage regeneration. Calcium
      channels that are regulated by physical stimuli seem to play a pivotal role in
      chondrogenic differentiation of MSCs. These channels increase intracellular
      calcium concentration, which leads to the initiation of the relevant cellular
      processes that are required for differentiation. This review will focus on the
      impact of different physical stimuli, including electrical,
      electromagnetic/magnetic and mechanical on various calcium channels and calcium
      signaling mechanisms during chondrogenic differentiation of hMSC.

PMID- 30275361
TI  - Local Deformation and Texture of Cold-Rolled AA6061 Aluminum Alloy.
AB  - Using cold rolling, we plastically deform AA6061 sheets at room temperature and
      investigate the variations of the microstructures, textures and local deformation
      of the cold-rolled AA6061 sheets as functions of thickness reduction (Deltat/t0,
      t0 and t are the thicknesses of the AA6061 sheet before and after the cold
      rolling, respectively). The volume fraction of total deformation texture is
      relatively independent of the thickness reduction for Deltat/t0 <= 30%, and
      becomes an approximately linearly increasing function of the thickness reduction
      for Deltat/t0 > 30%. Increasing the thickness reduction causes the increase of
      the Vickers hardness of the cross-section of the cold-rolled sheets, which
      exhibits a similar increase trend to the volume fraction of total deformation
      texture for Deltat/t0 > 30%. A simple relation between the Vickers hardness and
      the thickness reduction is established and is used to curve-fit the experimental
      results.

PMID- 30275362
TI  - Molecular Mechanisms of the Methionine Sulfoxide Reductase System from Neisseria
      meningitidis.
AB  - Neisseria meningitidis, an obligate pathogenic bacterium in humans, has acquired
      different defense mechanisms to detect and fight the oxidative stress generated
      by the host's defense during infection. A notable example of such a mechanism is
      the PilB reducing system, which repairs oxidatively-damaged methionine residues.
      This review will focus on the catalytic mechanism of the two methionine sulfoxide
      reductase (MSR) domains of PilB, which represent model enzymes for catalysis of
      the reduction of a sulfoxide function by thiols through sulfenic acid chemistry.
      The mechanism of recycling of these MSR domains by various "Trx-like" disulfide
      oxidoreductases will also be discussed.

PMID- 30275363
TI  - Ferroportin-Hepcidin Axis in Prepubertal Obese Children with Sufficient Daily
      Iron Intake.
AB  - Iron metabolism may be disrupted in obesity, therefore, the present study
      assessed the iron status, especially ferroportin and hepcidin concentrations, as
      well as associations between the ferroportin-hepcidin axis and other iron markers
      in prepubertal obese children. The following were determined: serum ferroportin,
      hepcidin, ferritin, soluble transferrin receptor (sTfR), iron concentrations and
      values of hematological parameters as well as the daily dietary intake in 40
      obese and 40 normal-weight children. The ferroportin/hepcidin and
      ferritin/hepcidin ratios were almost two-fold lower in obese children (p = 0.001;
      p = 0.026, respectively). Similar iron concentrations (13.2 vs. 15.2 umol/L, p =
      0.324), the sTfR/ferritin index (0.033 vs. 0.041, p = 0.384) and values of
      hematological parameters were found in obese and control groups, respectively.
      Iron daily intake in the obese children examined was consistent with
      recommendations. In this group, the ferroportin/hepcidin ratio positively
      correlated with energy intake (p = 0.012), dietary iron (p = 0.003) and vitamin
      B12 (p = 0.024). In the multivariate regression model an association between the
      ferroportin/hepcidin ratio and the sTfR/ferritin index in obese children (beta =
      0.399, p = 0.017) was found. These associations did not exist in the controls.
      The results obtained suggest that in obese children with sufficient iron intake,
      the altered ferroportin-hepcidin axis may occur without signs of iron deficiency
      or iron deficiency anemia. The role of other micronutrients, besides dietary
      iron, may also be considered in the iron status of these children.

PMID- 30275364
TI  - Peniginsengins B-E, New Farnesylcyclohexenones from the Deep Sea-Derived Fungus
      Penicillium sp. YPGA11.
AB  - Chemical examination of the EtOAc extract of the deep sea-derived fungus
      Penicillium sp. YPGA11 resulted in the isolation of four new
      farnesylcyclohexenones, peniginsengins B-E (1-4), and a known analog
      peniginsengin A (5). The structures of compounds 1-4 were determined on the basis
      of comprehensive analyses of the nuclear magnetic resonance (NMR) and mass
      spectroscopy (MS) data, and the absolute configurations of 1, 2, and 4 were
      determined by comparisons of experimental electronic circular dichroism (ECD)
      with calculated ECD spectra. Compounds 1-5, characterized by a highly oxygenated
      1-methylcyclohexene unit and a (4E,8E)-4,8-dimethyldeca-4,8-dienoic acid side
      chain, are rarely found in nature. Compounds 2-4 exhibited antibacterial activity
      against Staphylococcus aureus.

PMID- 30275365
TI  - Safety Lapses Prior to Initiation of Hemodialysis for Acute Kidney Injury in
      Hospitalized Patients: A Patient Safety Initiative.
AB  - Background: Safety lapses in hospitalized patients with acute kidney injury (AKI)
      may lead to hemodialysis (HD) being required before renal recovery might have
      otherwise occurred. We sought to identify safety lapses that, if prevented, could
      reduce the need for unnecessary HD after AKI; Methods: We conducted a
      retrospective observational study that included consecutive patients treated with
      HD for AKI at a large, tertiary academic center between 1 September 2015 and 31
      August 2016. Exposures of interest were pre-specified iatrogenic processes that
      could contribute to the need for HD after AKI, such as nephrotoxic medication or
      potassium supplement administration. Other outcomes included time from AKI
      diagnosis to initial management steps, including Nephrology referral; Results:
      After screening 344 charts, 80 patients were included for full chart review, and
      264 were excluded because they required HD within 72 h of admission, were deemed
      to have progression to end-stage kidney disease (ESKD), or required other renal
      replacement therapy (RRT) modalities in critical care settings such as continuous
      renal replacement therapy (CRRT) or sustained low efficiency dialysis (SLED).
      Multiple safety lapses were identified. Sixteen patients (20%) received an
      angiotensin converting enzyme inhibitor or angiotensin receptor blocker after AKI
      onset. Of 35 patients with an eventual diagnosis of pre-renal AKI due to
      hypovolemia, only 29 (83%) received a fluid bolus within 24 h. For 28 patients
      with hyperkalemia as an indication for starting HD, six (21%) had received a
      medication associated with hyperkalemia and 13 (46%) did not have a low potassium
      diet ordered. Nephrology consultation occurred after a median (IQR) time after
      AKI onset of 3.0 (1.0-5.7) days; Conclusions: Although the majority of patients
      had multiple indications for the initiation of HD for AKI, we identified many
      safety lapses related to the diagnosis and management of patients with AKI. We
      cannot conclude that HD initiation was avoidable, but, improving safety lapses
      may delay the need for HD initiation, thereby allowing more time for renal
      recovery. Thus, development of automated processes not only to identify AKI at an
      early stage but also to guide appropriate AKI management may improve renal
      recovery rates.

PMID- 30275366
TI  - Accurate Weed Mapping and Prescription Map Generation Based on Fully
      Convolutional Networks Using UAV Imagery.
AB  - Chemical control is necessary in order to control weed infestation and to ensure
      a rice yield. However, excessive use of herbicides has caused serious agronomic
      and environmental problems. Site specific weed management (SSWM) recommends an
      appropriate dose of herbicides according to the weed coverage, which may reduce
      the use of herbicides while enhancing their chemical effects. In the context of
      SSWM, the weed cover map and prescription map must be generated in order to carry
      out the accurate spraying. In this paper, high resolution unmanned aerial vehicle
      (UAV) imagery were captured over a rice field. Different workflows were evaluated
      to generate the weed cover map for the whole field. Fully convolutional networks
      (FCN) was applied for a pixel-level classification. Theoretical analysis and
      practical evaluation were carried out to seek for an architecture improvement and
      performance boost. A chessboard segmentation process was used to build the grid
      framework of the prescription map. The experimental results showed that the
      overall accuracy and mean intersection over union (mean IU) for weed mapping
      using FCN-4s were 0.9196 and 0.8473, and the total time (including the data
      collection and data processing) required to generate the weed cover map for the
      entire field (50 * 60 m) was less than half an hour. Different weed thresholds
      (0.00-0.25, with an interval of 0.05) were used for the prescription map
      generation. High accuracies (above 0.94) were observed for all of the threshold
      values, and the relevant herbicide saving ranged from 58.3% to 70.8%. All of the
      experimental results demonstrated that the method used in this work has the
      potential to produce an accurate weed cover map and prescription map in SSWM
      applications.

PMID- 30275367
TI  - Highly Integrated All-Fiber FP/FBG Sensor for Accurate Measurement of Strain
      under High Temperature.
AB  - Accurate measurement of strain is one of the most important issues for high
      temperature environments. We present a highly integrated all-fiber sensor to
      achieve precise measurements of strain/high-pressure, which consists of a fiber
      Bragg grating (FBG) inscribed by an 800 nm femtosecond laser cascaded with a
      micro extrinsic Fabry-Perot (FP) cavity fabricated by the 157 nm laser
      micromachining technique. FBG is sensitive to temperature, but insensitive to
      strain/pressure, whereas the FP is sensitive to strain/pressure, but has a small
      dependence on temperature. Therefore, such a cascaded sensor could be used for
      dual-parameter measurement and can work well at high temperatures. Experimental
      results indicate that this device exhibits a good strain characteristic at high
      temperatures and excellent high-pressure performance at room temperature. Due to
      its highly sensitive wavelength response, the proposed sensor will have
      remarkable potential applications in dual parameter sensing in harsh
      environments.

PMID- 30275369
TI  - Low-Cost Graphite on Paper Pressure Sensor for a Robot Gripper with a Trivial
      Fabrication Process.
AB  - A flexible pressure sensor with a rudimentary, ultra-low cost, and solvent-free
      fabrication process is presented in this paper. The sensor has a graphite-on
      paper stacked paper structure, which deforms and restores its shape when pressure
      is applied and released, showing an exceptionally fast response and relaxation
      time of ~0.4 ms with a sensitivity of -5%/Pa. Repeatability of the sensor over
      1000 cycles indicates an excellent long-term stability. The sensor demonstrated
      fast and reliable human touch interface, and successfully integrated into a robot
      gripper to detect grasping forces, showing high promise for use in robotics,
      human interface, and touch devices.

PMID- 30275368
TI  - Reduced Carotenoid and Retinoid Concentrations and Altered Lycopene Isomer Ratio
      in Plasma of Atopic Dermatitis Patients.
AB  - Carotenoids and retinoids are known to alter the allergic response with important
      physiological roles in the skin and the immune system. In the human organism
      various carotenoids are present, some of which are retinoid precursors. The
      bioactive derivatives of these retinoids are the retinoic acids, which can
      potently activate nuclear hormone receptors such as the retinoic acid receptor
      and the retinoid X receptor. In this study, we aimed to assess how plasma
      carotenoid and retinoid concentrations along with the ratio of their isomers are
      altered in atopic dermatitis (AD) patients (n = 20) compared to healthy
      volunteers (HV, n = 20). The study indicated that plasma levels of the
      carotenoids lutein (HV 198 +/- 14 ng/mL, AD 158 +/- 12 ng/mL, p = 0.02; all
      values in mean +/- SEM), zeaxanthin (HV 349 +/- 30 ng/mL, AD 236 +/- 18 ng/mL, p
      <= 0.01), as well as the retinoids retinol (HV 216 +/- 20 ng/mL, AD 167 +/- 17
      ng/mL, p = 0.04) and all-trans-retinoic acid (HV 1.1 +/- 0.1 ng/mL, AD 0.7 +/-
      0.1 ng/mL, p = 0.04) were significantly lower in the AD-patients, while lycopene
      isomers, alpha-carotene, and beta-carotene levels were comparable to that
      determined in the healthy volunteers. In addition, the ratios of 13-cis- vs. all
      trans-lycopene (HV 0.31 +/- 0.01, AD 0.45 +/- 0.07, p = 0.03) as well as 13-cis-
      vs. all-trans-retinoic acid (HV 1.4 +/- 0.2, AD 2.6 +/- 0.6, p = 0.03) were
      increased in the plasma of AD-patients indicating an AD-specific 13-cis
      isomerisation. A positive correlation with SCORAD was calculated with 13-cis- vs.
      all-trans-lycopene ratio (r = 0.40, p = 0.01), while a negative correlation was
      observed with zeaxanthin plasma levels (r = -0.42, p = 0.01). Based on our
      results, we conclude that in the plasma of AD-patients various carotenoids and
      retinoids are present at lower concentrations, while the ratio of selected
      lycopene isomers also differed in the AD-patient group. An increase in plasma
      isomers of both lycopene and retinoic acid may cause an altered activation of
      nuclear hormone receptor signaling pathways and thus may be partly responsible
      for the AD-phenotype.

PMID- 30275371
TI  - Correlations of Self-Reported Androgen Deficiency in Ageing Males (ADAM) with
      Stress and Sleep among Young Adult Males.
AB  - Androgen deficiency in males has traditionally been predominantly limited to
      older men aged 50+ years. However, little is known of the correlation between
      hormonal disruption, stress, and sleep in college-aged males. This cross
      sectional study investigates lifestyle behavior patterns in young men and a
      screening for potential androgen deficiency. A survey of 409 male students, as
      part of a larger USDA-funded GetFruved study, was analyzed for this subproject.
      Survey instruments used include the Androgen Deficiency in the Aging Male
      Questionnaire (ADAM) to assess for inadequate ADAM scores, the Perceived Stress
      Scale to measure stress levels and the Pittsburgh Sleep Quality Index to evaluate
      sleep quality. In total, 144 male participants (35%) met criteria for potential
      androgen deficiency defined by the ADAM questionnaire. Correlation was found
      between having a positive ADAM score and both increased stress levels (p < 0.001)
      and poor sleep quality (p < 0.001), with stress displaying the strongest effect
      (p < 0.001 vs p = 0.124). An increased prevalence of having a positive ADAM score
      versus established norms for this age group was also noted. These findings
      highlight the need for investigation of endocrine disruptions in young men.

PMID- 30275370
TI  - Impact of Sarcopenia as a Prognostic Biomarker of Bladder Cancer.
AB  - Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, indicates
      patient frailty and impaired physical function. Sarcopenia can be caused by
      multiple factors, including advanced age, lack of exercise, poor nutritional
      status, inflammatory diseases, endocrine diseases, and malignancies. In patients
      with cancer cachexia, anorexia, poor nutrition and systemic inflammation make the
      metabolic state more catabolic, resulting in sarcopenia. Thus, sarcopenia is
      considered as one of manifestations of cancer cachexia. Recently, growing
      evidence has indicated the importance of sarcopenia in the management of patients
      with various cancers. Sarcopenia is associated with not only higher rates of
      treatment-related complications but also worse prognosis in cancer-bearing
      patients. In this article, we summarized metabolic backgrounds of cancer cachexia
      and sarcopenia and definitions of sarcopenia based on computed tomography (CT)
      images. We conducted a systematic literature review regarding the significance of
      sarcopenia as a prognostic biomarker of bladder cancer. We also reviewed recent
      studies focusing on the prognostic role of changes in skeletal muscle mass during
      the course of treatment in bladder cancer patients. Lastly, we discussed the
      impact of nutritional support, medication, and exercise on sarcopenia in cancer
      bearing patients.

PMID- 30275372
TI  - Metal-Organic Framework Thin Film-Based Dye Sensitized Solar Cells with Enhanced
      Photocurrent.
AB  - Metal-organic framework thin film-based dye sensitized solar cell is fabricated
      with highly oriented, crystalline, and porous Zn-perylene metal-organic framework
      (MOF) thin film (SURMOF) which is integrated with Bodipy embedded in poly(methyl
      methacrylate). It has been demonstrated that the photocurrent can be enhanced by
      a factor of 5 relative to Zn-perylene MOF thin film due to triplet-triplet
      annihilation up-conversion between the Bodipy/PMMA sensitizer and the Zn-perylene
      MOF thin film acceptor using Co(bpy)32+/3+ as redox mediator.

PMID- 30275373
TI  - Enhancing the Number of Modes in Metasurfaced Reverberation Chambers for Field
      Uniformity Improvement.
AB  - The use of metasurfaces to increase the number of modes, lower the operating
      frequency, and improve the field uniformity in reverberation chambers (RCs) is
      investigated in this paper. The method used to improve the field uniformity and
      decrease the resonance frequencies is based on increasing the number of modes by
      using the concept of subwavelength cavities. The resonance frequencies of a RC
      with metasurface wall are derived and expressed analytically in terms of
      macroscopic characteristics. Simulation of the reflection phase of the unit cell
      is then given as a guideline to choose the required microscopic parameters of the
      designed metasurface. The mode density in such subwavelength RCs is then obtained
      using a numerical eigenmode solver. Compared to traditional RCs, a much higher
      modal density is obtained at low frequencies. The standard deviation of the field
      uniformity in the test volume of the RC corresponding to different types of
      metasurface walls is finally compared. It is shown that by increasing the number
      of modes in the RC at the lower band, the operating frequency decreases and the
      field uniformity of the RC is improved.

PMID- 30275374
TI  - Privacy and Well-Being in Aged Care Facilities with a Crowded Living Environment:
      Case Study of Hong Kong Care and Attention Homes.
AB  - This study aims to understand the relationship between bedroom privacy and well
      being of the elderly in aged care facilities with a compact living situation. A
      majority of studies on this topic were carried out in a low-density population
      context. The crowded living situation might compromise the well-being of
      residents. This study proposed five architectural parameters to measure bedroom
      privacy in aged care facilities: total open surface per unit, openness/solid
      ratio per bed, height of partition wall, number of people per unit, and personal
      control over bedroom privacy. SF-12 v.2 Health Survey was used to collect
      information on physical and mental health status. The study surveyed nine Care &
      Attention homes and their 213 residents in Hong Kong. The total open surface per
      unit and the openness/solid ratio per bed were positively associated with the
      physical health of residents. The height of partition walls was associated
      negatively with their physical and mental health conditions, and the number of
      people per unit was negatively associated with their physical health. More than
      half of respondents preferred a single unit with high partition walls; however,
      40% of respondents preferred low partition walls. The provision of privacy for
      the elderly should be balanced with their needs for social interactions; total
      open surface per unit, openness/solid ratio per bed and height of partition wall
      should be taken into consideration. The study provides evidence and design
      guidelines for improving privacy in aged care facilities with a compact living
      environment.

PMID- 30275375
TI  - Mechanical Metamaterials Foams with Tunable Negative Poisson's Ratio for Enhanced
      Energy Absorption and Damage Resistance.
AB  - Systematic and deep understanding of mechanical properties of the negative
      Poisson's ratio convex-concave foams plays a very important role for their
      practical engineering applications. However, in the open literature, only a
      negative Poisson's ratio effect of the metamaterials convex-concave foams is
      simply mentioned. In this paper, through the experimental and finite element
      methods, effects of geometrical morphology on elastic moduli, energy absorption,
      and damage properties of the convex-concave foams are systematically studied.
      Results show that negative Poisson's ratio, energy absorption, and damage
      properties of the convex-concave foams could be tuned simultaneously through
      adjusting the chord height to span ratio of the sine-shaped cell edges. By the
      rational design of the negative Poisson's ratio, when compared to the
      conventional open-cell foams of equal mass, convex-concave foams could have the
      combined advantages of relative high stiffness and strength, enhanced energy
      absorption and damage resistance. The research of this paper provides theoretical
      foundations for optimization design of the mechanical properties of the convex
      concave foams and thus could facilitate their practical applications in the
      engineering fields.

PMID- 30275376
TI  - Highly Efficient Targeted Gene Editing in Upland Cotton Using the CRISPR/Cas9
      System.
AB  - The clustered regularly interspaced short palindromic repeats/CRISPR-associated
      protein 9 (CRISPR/Cas9) gene editing system has been shown to be able to induce
      highly efficient mutagenesis in the targeted DNA of many plants, including
      cotton, and has become an important tool for investigation of gene function and
      crop improvement. Here, we developed a simple and easy to operate CRISPR/Cas9
      system and demonstrated its high editing efficiency in cotton by targeting-ALARP,
      a gene encoding alanine-rich protein that is preferentially expressed in cotton
      fibers. Based on sequence analysis of the target site in the 10 transgenic
      cottons containing CRISPR/Cas9, we found that the mutation frequencies of GhALARP
      A and GhALARP-D target sites were 71.4-100% and 92.9-100%, respectively. The most
      common editing event was deletion, but deletion together with large insertion was
      also observed. Mosaic mutation editing events were detected in most transgenic
      plants. No off-target mutation event was detected in any the 15 predicted sites
      analyzed. This study provided mutants for further study of the function of
      GhALARP in cotton fiber development. Our results further demonstrated the
      feasibility of use of CRISPR/Cas9 as a targeted mutagenesis tool in cotton, and
      provided an efficient tool for targeted mutagenesis and functional genomics in
      cotton.

PMID- 30275377
TI  - Decreased Capacity for Sperm Production Induced by Perinatal Bisphenol A Exposure
      Is Associated with an Increased Inflammatory Response in the Offspring of C57BL/6
      Male Mice.
AB  - Many previous studies have indicated the adverse effects of bisphenol A (BPA) on
      sperm production and quality; however, the mechanisms underlying BPA male
      reproductive toxicity have yet to be elucidated. The main purpose of this study
      was to investigate the effect of perinatal exposure to BPA on the spermatogenic
      capacity of male offspring, and to explore the possible influence of inflammatory
      responses in BPA reproductive toxicity. Twenty-one pregnant C57BL/6mice were
      randomly divided into three groups: a control group, a group receiving 0.2 MUg/mL
      (LBPA), and a group receiving 2 MUg/mL of BPA (HBPA), all via drinking water from
      gestational day 6 to the end of lactation. After weaning, one male mouse was
      randomly selected from each group (n = 7/group); these three mice were fed a
      normal diet and drinking water for 1 month. Levels of serum testosterone (T) and
      tumor necrosis factor (TNF)-alpha were then measured in all mice. Sperm count and
      the proportion of sperm malformation were also determined. The levels of Toll
      like receptor 4 (TLR4), nuclear factor (NF)-kappaB, and aryl hydrocarbon receptor
      (AhR) protein expression in the testis tissue were determined. Analysis showed
      that the proportion of sperm malformation increased in the LBPA and HBPA groups
      (p < 0.05). Sperm count significantly decreased only in the HBPA group (p <
      0.05), while the levels of serum TNF-alpha increased in the LBPA and HBPA groups
      (p < 0.05). Levels of serum T decreased significantly in the HBPA group, compared
      with controls (p < 0.05). Levels of TLR4 and NF-kappaB protein expression in the
      testis were significantly higher in the LBPA and HBPA groups (p < 0.05 or p <
      0.01), while AhR protein expression was higher and seminiferous tubules in the
      testis showed more damage in the HBPA group compared to controls (p < 0.05 and p
      < 0.01, respectively). Our results showed that perinatal exposure to low or high
      doses of BPA decreased the capacity for spermatogenesis in male offspring, which
      may be associated with an inflammatory response activated by the TLR4/ NF-kappaB
      and AhR signaling pathways in the testis.

PMID- 30275378
TI  - Extensive Contamination of Water with Saxitoxin Near the Dam of the Irkutsk
      Hydropower Station Reservoir (East Siberia, Russia).
AB  - An area of discolored water 50 m wide and 30 m long was found in September 2017
      close to the dam of the Irkutsk hydroelectric power station. Water from this spot
      was sampled for investigation in the present study. Microscopic analysis revealed
      that the suspended matter in the sample was composed of clumps of filaments,
      vegetative cells, akinetes and heterocysts that formed short filaments and
      solitary cells. This matter was found to consist of partially degraded cells of
      the cyanobacterium Dolichospermum lemmermannii. Nucleotide sequencing of DNA
      isolated from the biomass revealed the presence of the sxtA gene which is
      involved in the synthesis of saxitoxin. Water from the polluted area contained
      600 +/- 100 MUg L-1 saxitoxin as measured by HPLC-MS with pre-column modification
      of the toxin with 2,4-dinitrophenylhydrazine. Immunoassay analysis (ELISA) showed
      a concentration of saxitoxins in the water of 2900 +/- 900 MUg L-1. Hydrochemical
      and microbiological analyses suggested the contaminated area appeared as a result
      of a D. lemmermannii bloom, followed by its decay and release of saxitoxin and
      nutrients. The present paper describes the results of a case study. Better
      understanding of the phenomenon will depend on the possibility to perform
      implementation of a large-scale monitoring program.

PMID- 30275379
TI  - The Impact of Health Insurance Policy on the Health of the Senior Floating
      Population-Evidence from China.
AB  - The impact of health insurance on residents' health is one of the focal points of
      academic research. Due to the fact that China's medical insurance system is
      composed of a variety of programs and that the pooling districts are at the lower
      administrative level, enrollment in different medical insurance programs or at
      different places may have certain influences on the health of residents. This has
      mostly been neglected by previous studies. This paper uses data from the 2015
      China Migrants Dynamic Survey (CMDS), focusing on the senior floating population
      and taking the difference in government subsidy proportions as an instrumental
      variable in order to identify the effects of health insurance programs and
      regional differences on the health of the senior floating population. Three
      effects were observed: First, participation in the health insurance system
      significantly improves floating seniors' self-rated health. Second, the health
      status of floating seniors affects their choice of health insurance program: Less
      healthy persons tend to choose high-paying, wide-coverage basic medical insurance
      available for urban employees. Using an instrumental variable to control for the
      problem of endogeneity, it is discovered that compared with the basic medical
      insurance system for urban residents, the system for urban employees
      significantly enhances the health of the senior floating population. Third,
      "adverse selection" could be observed in the choice between enrolling in health
      insurance at the place of settlement or another place. Senior migrants with worse
      self-rated health tend to choose place of settlement in order to enjoy higher
      compensation and less complex reimbursement procedures. With an instrumental
      variable to control for the problem of endogeneity, it was found that compared
      with joining the medical insurance system at other places, joining at a place of
      settlement could improve the health of the floating senior population.

PMID- 30275381
TI  - A Study on the Effect of Ultrasonic Treatment on the Microstructure of Sn-30 wt.%
      Bi Alloy.
AB  - The effect of ultrasonic treatment on the microstructure of Sn-30 wt.% Bi alloy
      was studied at different temperatures. Results showed that the ultrasonic
      treatment could effectively refine the microstructure of Sn-30 wt.% Bi alloy at a
      temperature range between the liquidus and solidus. Application of the ultrasound
      could fragment the primary Sn dendrites during solidification due to a mixed
      effect of ultrasonic cavitation and acoustic streaming. The divorced eutectic
      formed when the ultrasonic treatment was applied for the whole duration of the
      solidification. The eutectic phase grew and surrounded the primary Sn dendrite,
      and pure Bi phase grew in between the Sn dendritic fragments. The mechanism of
      the fragmentation of dendrites and the divorced eutectic structure by ultrasonic
      treatment was discussed.

PMID- 30275380
TI  - Impact of Coffee, Wine, and Chocolate Consumption on Cognitive Outcome and MRI
      Parameters in Old Age.
AB  - Coffee, wine and chocolate are three frequently consumed substances with a
      significant impact on cognition. In order to define the structural and cerebral
      blood flow correlates of self-reported consumption of coffee, wine and chocolate
      in old age, we assessed cognition and brain MRI measures in 145 community-based
      elderly individuals with preserved cognition (69 to 86 years). Based on two
      neuropsychological assessments during a 3-year follow-up, individuals were
      classified into stable-stable (52 sCON), intermediate (61 iCON) and deteriorating
      deteriorating (32 dCON). MR imaging included voxel-based morphometry (VBM), tract
      based spatial statistics (TBSS) and arterial spin labelling (ASL). Concerning
      behavior, moderate consumption of caffeine was related to better cognitive
      outcome. In contrast, increased consumption of wine was related to an unfavorable
      cognitive evolution. Concerning MRI, we observed a negative correlation of wine
      and VBM in bilateral deep white matter (WM) regions across all individuals,
      indicating less WM lesions. Only in sCON individuals, we observed a similar yet
      weaker association with caffeine. Moreover, again only in sCON individuals, we
      observed a significant positive correlation between ASL and wine in overlapping
      left parietal WM indicating better baseline brain perfusion. In conclusion, the
      present observations demonstrate an inverse association of wine and coffee
      consumption with cognitive performances. Moreover, low consumption of wine but
      also moderate to heavy coffee drinking was associated with better WM preservation
      and cerebral blood-flow notably in cognitively stable elders.

PMID- 30275382
TI  - High-Performance Thin Film Transistor with an Neodymium-Doped Indium Zinc
      Oxide/Al2O3 Nanolaminate Structure Processed at Room Temperature.
AB  - In this work, a high-performance thin film transistor with an neodymium-doped
      indium zinc oxide (Nd:IZO) semiconductor via a room temperature approach and
      adopting the Nd:IZO/Al2O3 nanolaminate structure was investigated. The effects of
      the ultrathin Al2O3 layer and the thickness of Nd:IZO layer in the nanolaminate
      structure on the improvement of electrical performance and stability of thin film
      transistors (TFTs) were systematically studied. Besides the carrier movement
      confined along the near-channel region, driven by the Al2O3 layer under an
      electrical field, the high performance of the TFT is also attributed to the high
      quality of the 8-nm-thick Nd:IZO layer and the corresponding optimal Nd:IZO/Al2O3
      interface, which reduce the scattering effect and charge trapping with strong M-O
      bonds in bulk and the back-channel surface of Nd:IZO, according to the X-ray
      reflectivity (XRR), X-ray photoelectron spectroscopy (XPS), and micro-wave photo
      conductivity decay (MU-PCD) results. As a result, the Nd:IZO/Al2O3 TFT exhibits
      an outstanding performance, with a high MUsat of 32.7 cm2.V-1.s-1, an Ion/Ioff of
      1.9 * 108, and a low subthreshold swing (SS) value of 0.33 V.dec-1, which shows
      great potential for the room temperature fabrication of TFTs in high-resolution
      or high-frame-rate displays by a scalable, simple, and feasible approach.

PMID- 30275384
TI  - Short-Term Effects of Ambient Air Pollution on Hospitalization for Respiratory
      Disease in Taiyuan, China: A Time-Series Analysis.
AB  - In this study, we estimated the short-term effects of ambient air pollution on
      respiratory disease hospitalization in Taiyuan, China. Daily data of respiratory
      disease hospitalization, daily concentration of ambient air pollutants and
      meteorological factors from 1 October 2014 to 30 September 2017 in Taiyuan were
      included in our study. We conducted a time-series study design and applied a
      generalized additive model to evaluate the association between every 10-MUg/m3
      increment of air pollutants and percent increase of respiratory disease
      hospitalization. A total of 127,565 respiratory disease hospitalization cases
      were included in this study during the present period. In single-pollutant
      models, the effect values in multi-day lags were greater than those in single-day
      lags. PM2.5 at lag02 days, SO2 at lag03 days, PM10 and NO2 at lag05 days were
      observed to be strongly and significantly associated with respiratory disease
      hospitalization. No significant association was found between O3 and respiratory
      disease hospitalization. SO2 and NO2 were still significantly associated with
      hospitalization after adjusting for PM2.5 or PM10 into two-pollutant models.
      Females and younger population for respiratory disease were more vulnerable to
      air pollution than males and older groups. Therefore, some effective measures
      should be taken to strengthen the management of the ambient air pollutants,
      especially SO2 and NO2, and to enhance the protection of the high-risk population
      from air pollutants, thereby reducing the burden of respiratory disease caused by
      ambient air pollution.

PMID- 30275385
TI  - Ghrelin in Serum and Urine of Post-Partum Women with Gestational Diabetes
      Mellitus.
AB  - Women with a previous history of gestational diabetes mellitus (GDM) have a
      significantly increased risk of developing type 2 diabetes, obesity, and
      cardiovascular diseases in the future. The aim of the study was to evaluate
      ghrelin concentrations in serum and urine in the GDM group in the early post
      partum period, with reference to laboratory results, body composition, and
      hydration status. The study subjects were divided into two groups, that is, 28
      healthy controls and 26 patients with diagnosed GDM. The maternal body
      composition and hydration status were evaluated by the bioelectrical impedance
      analysis (BIA) method. The concentrations of ghrelin in the maternal serum and
      urine were determined via enzyme-linked immunosorbent assay (ELISA). The
      laboratory and BIA results of the mothers with GDM were different from those
      without GDM. Urine ghrelin positively correlated with serum ghrelin and high
      density lipoprotein cholesterol (HDL) levels in healthy mothers. There were
      direct correlations between urine ghrelin and HDL as well as triglycerides levels
      in the GDM group. Neither the lean tissue index nor body cell mass index were
      related to the serum ghrelin concentrations in this group. Only the urine ghrelin
      of healthy mothers correlated with the fat tissue index. Our results draw
      attention to urine as an easily available and appropriable biological material
      for further studies.

PMID- 30275383
TI  - Branched-Chain Amino Acid Database Integrated in MEDIPAD Software as a Tool for
      Nutritional Investigation of Mediterranean Populations.
AB  - Branched-chained amino acids (BCAA) are essential dietary components for humans
      and can act as potential biomarkers for diabetes development. To efficiently
      estimate dietary intake, we developed a BCAA database for 1331 food items found
      in the French Centre d'Information sur la Qualite des Aliments (CIQUAL) food
      table by compiling BCAA content from international tables, published
      measurements, or by food similarity as well as by calculating 267 items from
      Greek, Turkish, Romanian, and Moroccan mixed dishes. The database embedded in
      MEDIPAD software capable of registering 24 h of dietary recalls (24HDR) with
      clinical and genetic data was evaluated based on archived 24HDR of the Saint
      Pierre Institute (France) from 2957 subjects, which indicated a BCAA content up
      to 4.2 g/100 g of food and differences among normal weight and obese subjects
      across BCAA quartiles. We also evaluated the database of 119 interviews of
      Romanians, Turkish and Albanians in Greece (27-65 years) during the MEDIGENE
      program, which indicated mean BCAA intake of 13.84 and 12.91 g/day in males and
      females, respectively, comparable to other studies. The MEDIPAD is user-friendly,
      multilingual, and secure software and with the BCAA database is suitable for
      conducting nutritional assessment in the Mediterranean area with particular
      facilities for food administration.

PMID- 30275386
TI  - Erythrocyte Saturated Fatty Acids and Incident Type 2 Diabetes in Chinese Men and
      Women: A Prospective Cohort Study.
AB  - The association between circulating saturated fatty acids (SFAs) and incident
      type 2 diabetes (T2D) is reported in Western populations with inconsistent
      results, while evidence from Asian populations is scarce. We aimed to examine the
      associations between erythrocyte SFAs and incident T2D in a Chinese population.
      Between 2008 and 2013, a total of 2683 participants, aged 40-75 years, free of
      diabetes were included in the present analyses. Incident T2D cases were
      ascertained during follow-up visits. Gas chromatography was used to measure
      erythrocyte fatty acids at baseline. The Cox proportional hazards model was used
      to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). During
      13,508 person years of follow-up, 216 T2D cases were identified. Compared with
      the first quartile, multivariable-adjusted HRs (95% CIs) of the fourth quartile
      were 1.20 (0.82-1.76; p = 0.242) for myristic acid (14-carbon tail, zero double
      bonds; 14:0), 0.69 (0.48-0.99; p = 0.080) for palmitic acid (16:0), 1.49 (1.02
      2.19; p = 0.047) for stearic acid (18:0), 1.46 (1.00-2.12; p = 0.035) for
      arachidic acid (20:0), 1.48 (0.99-2.22; p = 0.061) for behenic acid (22:0), and
      1.08 (0.74-1.56; p = 0.913) for lignoceric acid (24:0). Our findings indicate
      that individual erythrocyte SFAs are associated with T2D in different directions,
      with 18:0 and 20:0 SFAs positively associated with the risk, whereas no
      convincing inverse association for 16:0 SFAs.

PMID- 30275387
TI  - The Dislike of Hot Thermal Conditions and Its Relationship with Sun (Ultraviolet
      Radiation) Exposure in the Southeastern United States.
AB  - We investigated the relationship between peoples' preferences for being outside
      during certain months of the year, based upon their dislike of hot or warm
      temperatures, and of taking precautions against ultraviolet radiation (UVR)
      exposure. A sample of university undergraduates (N = 1400) living in the Northern
      Hemisphere completed an online survey in the late summer of 2017 that inventoried
      their dislike of heat and hot conditions, their sun tanning preferences and
      habits, and their preferences for being outside during different months of the
      year, along with whether they would protect themselves from the UVR exposure
      during those months. Dislike of hot conditions was negatively correlated with
      respondent preferences for sun tanning and with the number of months during the
      year that people enjoyed being active outside. A greater proportion of people who
      disliked hot conditions experienced risks of UVR overexposure during the spring
      and fall. In contrast, people who expressed more liking of heat frequently
      enjoyed being outside during the warmer months (April to October), and a
      significantly greater proportion of them experienced risks for sun overexposure
      in these months. Such individual differences in heat-related attitudes may
      explain a proportion the variability in individual risk behaviors for skin cancer
      that is not currently accounted for by approaches using objective variables such
      as temperature, thermal comfort indices, or the UV index.

PMID- 30275388
TI  - AbeTx1 Is a Novel Sea Anemone Toxin with a Dual Mechanism of Action on Shaker
      Type K+ Channels Activation.
AB  - Voltage-gated potassium (KV) channels regulate diverse physiological processes
      and are an important target for developing novel therapeutic approaches. Sea
      anemone (Cnidaria, Anthozoa) venoms comprise a highly complex mixture of peptide
      toxins with diverse and selective pharmacology on KV channels. From the
      nematocysts of the sea anemone Actinia bermudensis, a peptide that we named
      AbeTx1 was purified and functionally characterized on 12 different subtypes of KV
      channels (KV1.1-KV1.6; KV2.1; KV3.1; KV4.2; KV4.3; KV11.1; and, Shaker IR), and
      three voltage-gated sodium channel isoforms (NaV1.2, NaV1.4, and BgNaV). AbeTx1
      was selective for Shaker-related K+ channels and is capable of inhibiting K+
      currents, not only by blocking the K+ current of KV1.2 subtype, but by altering
      the energetics of activation of KV1.1 and KV1.6. Moreover, experiments using six
      synthetic alanine point-mutated analogs further showed that a ring of basic amino
      acids acts as a multipoint interaction for the binding of the toxin to the
      channel. The AbeTx1 primary sequence is composed of 17 amino acids with a high
      proportion of lysines and arginines, including two disulfide bridges (Cys1-Cys4
      and Cys2-Cys3), and it is devoid of aromatic or aliphatic amino acids. Secondary
      structure analysis reveals that AbeTx1 has a highly flexible, random-coil-like
      conformation, but with a tendency of structuring in the beta sheet. Its overall
      structure is similar to open-ended cyclic peptides found on the scorpion kappa
      KTx toxins family, cone snail venoms, and antimicrobial peptides.

PMID- 30275389
TI  - Removal of Cr (VI) from Simulated and Leachate Wastewaters by Bentonite-Supported
      Zero-Valent Iron Nanoparticles.
AB  - Zero-valent iron (Fe0) nanoparticles (NPs) have shown excellent ability to remove
      contaminants hexavalent chromium (Cr(VI)) from aquatic systems. Use of support
      materials can help to prevent oxidation and aggregation of Fe0NPs, and thus
      enhance their remediation efficiency. However, most previous studies were
      conducted using artificially synthetic wastewater, and little is known on the
      remediation effects of supported Fe0NPs on actual wastewaters containing Cr(VI).
      Here, bentonite-supported Fe0NPs (BFe0NPs) with 1-5% of bentonite were prepared
      and characterized using scanning electron microscopy (SEM) and X-ray diffraction
      (XRD) techniques. Batch experiments were performed to study Cr(VI) removal by the
      selected BFe0NPs from a simulated wastewater and a leachate wastewater
      originating from a Cr slag heap-polluted soil. The results show that Fe0NPs were
      uniformly dispersed on the bentonite, leading to a decreased aggregation of NPs,
      and the optimal mass ratio of bentonite was 4%. Batch experiment results show
      that lower pH values favored Cr(VI) removal by BFe0NPs. The removal percentage of
      Cr(VI) was higher than 90% for both wastewaters when the pH value was 2.0, but
      decreased significantly as pH value increased. Cr(VI) removal reaction was quite
      fast within the initial 10 min, and at least 85% of Cr(VI) was removed for both
      wastewaters. Cr(VI) removal percentage increased with increasing BFe0NPs dosages
      ranging from 30 to 60, but remained almost unchanged when the Fe/Cr mass ratio
      increased to above 60. The reaction of BFe0NPs to remove Cr(VI) followed the
      pseudo second-order reaction model. In most cases, the removal rates of Cr(VI)
      were higher in simulated wastewater than in leachate wastewater, but all
      approached 100% at the optimal conditions. Our present results show that BFe0NPs
      with 4% bentonite are efficient for treatment of Cr(VI)-containing wastewaters.

PMID- 30275390
TI  - Development of an Oral Compound Pickering Emulsion Composed of Nanocrystals of
      Poorly Soluble Ingredient and Volatile Oils from Traditional Chinese Medicine.
AB  - In this study, an oral drug nanocrystals self-stabilized Pickering emulsion
      (NSSPE), which used nanocrystals of a poorly soluble ingredient from Puerariae
      Radix called puerarin as solid particle stabilizers and Ligusticum chuanxiong
      essential oil since the main oil phase had been developed to improve the oral
      bioavailability of puerarin. The appearance of emulsions, size and zeta potential
      of droplets, and content of puerarin in emulsified layer during a storage of six
      months at 4, 25, and 40  degrees C were investigated. The centrifugation
      stability at 4000* g was also studied. The micro-structure of emulsion droplets
      was characterized by a scanning electron micrograph (SEM), confocal laser
      scanning microscopy (CLSM), a fluorescence microscope (FM), and differential
      scanning calorimetry (DSC). The in vivo oral bioavailability of puerarin NSSPE
      was investigated in rats. Results showed that appearances of puerarin NSSPE kept
      stable after centrifugation at 4000* g for 15 min or storage for six months at 4,
      25, and 40  degrees C. SEM, CLSM, FM, and DSC showed that the puerarin NSSPE had
      a stable core-shell structure of emulsion droplets formed by the adsorption of
      puerarin nanocrystals on the surface of oil droplets of mixed oil of Ligusticum
      chuanxiong essential oil and Labrafil M 1944 CS (9:1, v/v). The relative
      bioavailability of puerarin NSSPE to puerarin coarse powder suspension,
      nanocrystal suspension, and surfactant emulsion were 262.43%, 155.92%, and
      223.65%, respectively. All these results indicated that puerarin nanocrystals
      could stabilize Pickering emulsion of Ligusticum chuanxiong essential oil without
      any other stabilizers and Pickering emulsion could improve the oral
      bioavailability of puerarin, which suggests that the drug nanocrystal self
      stabilized Pickering emulsion as a promising oral drug delivery system for
      Traditional Chinese Medicine containing poorly soluble ingredients and volatile
      oils.

PMID- 30275391
TI  - Aurantoside C Targets and Induces Apoptosis in Triple Negative Breast Cancer
      Cells.
AB  - Triple negative breast cancer (TNBC) is a subtype of breast cancers that
      currently lacks effective targeted therapy. In this study, we found that
      aurantoside C (C828), isolated from the marine sponge Manihinea lynbeazleyae
      collected from Western Australia, exhibited higher cytotoxic activities in TNBC
      cells compared with non-TNBC (luminal and normal-like) cells. The cytotoxic
      effect of C828 was associated to the accumulation of cell at S-phase, resulting
      in the decline of cyclin D1, cyclin E1, CDK4, and CDK6, and an increase in p21.
      We also found that C828 inhibited the phosphorylation of Akt/mTOR and NF-kB
      pathways and increased the phosphorylation of p38 MAPK and SAPK/JNK pathways,
      leading to apoptosis in TNBC cells. These effects of C828 were not observed in
      non-TNBC cells at the concentrations that were cytotoxic to TNBC cells. When
      compared to the cytotoxic effect with the chemotherapeutic drugs doxorubicin and
      cisplatin, C828 was found to be 20 times and 35 times more potent than
      doxorubicin and cisplatin, respectively. These results indicate that C828 could
      be a promising lead for developing new anticancer agents that target TNBC cells.

PMID- 30275393
TI  - Reinforcement of Stearic Acid Treated Egg Shell Particles in Epoxy Thermosets:
      Structural, Thermal, and Mechanical Characterization.
AB  - This work reports the modification of egg shell (ES) particles by using stearic
      acid (SA) and their reinforcement in the epoxy matrix. The ES treatment via SA
      was optimized, the optimum conditions for concentration, temperature, and time
      were found to be 2.5%, 85  degrees C, and 50 min, respectively. The untreated ES
      (UES) and treated ES (TES) particles were characterized by Fourier transform
      infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray
      diffraction (XRD), scanning electron microscope (SEM), particle size
      distribution, and contact angle. FTIR confirmed the chemical modification of SA
      on ES surface and DSC reflects an endothermic peak at 240  degrees C. XRD reveal
      a decrease in crystal size and crystallinity, while contact angle increases to
      169 degrees  from 42 degrees . The SEM observations clearly reflect a distinct
      decrease and separation of small domains of ES particles thus improving an
      increased surface area. Afterwards, the UES and TES particles were reinforced in
      epoxy at 15 and 20 weight (wt.) % loading. The tensile tests confirmed a 22%
      increase in elongation as compared to pure epoxy due to the hydrogen bonding
      between TES particles and matrix. The lowest brittleness was recorded for
      TES/epoxy composites on 20 wt % loading. The TGA confirmed the improved thermal
      stabilities at 20 wt % loading of TES particles in matrix, the improvements in
      T5%, T10%, and T20% values were recorded as 33, 26, and 21  degrees C higher than
      the corresponding values for neat matrix. The TES/epoxy composites on 20 wt %
      showed 41% increase in storage modulus as compared to the pristine epoxy, and
      cross-link density reaches to 2.71 * 10-3 from 1.29 * 10-3 mol/cm3 for neat
      matrix. The decline in tan delta height and improvement in Tg were also observed.
      The best adhesion effectiveness was recorded for TES/epoxy composites. This
      simple and economical modification technique can enhance the application of ES
      particles in various polymeric coating and composites applications.

PMID- 30275394
TI  - Interlaminar Shear Properties of Z-Pinned Carbon Fiber Reinforced Aluminum Matrix
      Composites by Short-Beam Shear Test.
AB  - This paper presents the effect of through-thickness reinforcement by steel z-pins
      on the interlaminar shear properties and strengthening mechanisms of carbon fiber
      reinforced aluminum matrix composites (Cf/Al) with a short beam shear test
      method. Microstructural analysis reveals that z-pins cause minor microstructural
      damage including to fiber waviness and aluminum-rich regions, and interface
      reaction causes a strong interface between the stainless steel pin and the
      aluminum matrix. Z-pinned Cf/Al composites show reduced apparent interlaminar
      shear strength due to a change in the failure mode compared to unpinned
      specimens. The changed failure mode could result from decreased flexural strength
      due to microstructural damage as well as increased actual interlaminar shear
      strength. Fracture work is improved significantly with a z-pin diameter. The
      strong interface allows the deformation resistance of the steel pin to contribute
      to the crack bridging forces, which greatly enhances the interlaminar shear
      properties.

PMID- 30275395
TI  - Chemical Composition, Antioxidant Activity and alpha-Glucosidase Inhibitory
      Activity of Chaenomeles Speciosa from Four Production Areas in China.
AB  - Chaenomeles speciosa (Sweet) Nakai is a medicinal plant. Until date, there are no
      studies focusing on comparing the chemical profiles, antioxidant activity and
      alpha-glucosidase inhibitory activity of the dried fruits of C. speciosa from
      different production regions. In the study, we investigated the chemical
      components of dried fruits of C. speciosa from Yunnan, Chongqing, Zhejiang and
      Anhui provinces in China in relation to the antioxidant activity and alpha
      glucosidase inhibitory activity. C. speciosa from Yunnan had higher total
      flavonoid (47.92 +/- 3.79 mg/g), total polyphenol (29.15 +/- 0.29 mg/g) and
      polysaccharide (27.60 +/- 1.56 mg/g) contents than plants from other production
      areas. Samples from Yunnan, Zhejiang and Anhui (all > 3200 mg/kg) had higher free
      amino acid contents than those from Chongqing (2286.66 mg/kg). Oleanolic acid and
      ursolic acid levels were highest in samples from Zhejiang (555.98 +/- 20.88
      MUg/g) and Anhui (321.06 +/- 14.64 MUg/g), respectively. C. speciosa from
      Chongqing had low total flavonoid, total polyphenol, polysaccharide, free amino
      acid, oleanolic acid and ursolic acid contents but high levels of palmitic acid
      (12.04 +/- 0.02 mg/g) and stearic acid (2.23 +/- 0.08 mg/g). Among four
      production areas, Yunnan represented the highest antioxidant activity and alpha
      glucosidase inhibitory activity. In addition, correlation analysis revealed that
      total flavonoid, total polyphenol, polysaccharide and ursolic acid were the major
      components responsible for the antioxidant activity of C. speciosa, while total
      flavonoid and polysaccharide were the main contributors for alpha-glucosidase
      inhibitory activity of the plant. These results would be helpful for evaluating
      the quality of C. speciosa in the different production areas.

PMID- 30275396
TI  - Influence of Dielectric Barrier Discharge Treatment on Surface Structure of
      Polyoxymethylene Fiber and Interfacial Interaction with Cement.
AB  - Polyoxymethylene (POM) fiber was treated with atmospheric dielectric barrier
      discharge (DBD) plasma to enhance the surface activity of the fiber and
      interfacial interaction with cement. The physical and chemical properties of
      samples with different DBD plasma treatment durations were tested and analyzed.
      Scanning electron microscopy (SEM) and atomic force microscopy (AFM) revealed
      that the surface roughness of the sample increased significantly as a result of
      the DBD plasma treatment. Fourier transform infrared spectrophotometer (FTIR) and
      X-ray photoelectron spectroscopy (XPS) analysis showed that a large number of 
      COH and -COOH groups were formed on the surface of the sample after DBD plasma
      treatment. The hydrophilicity of the POM fiber was greatly improved with the
      increase in the treatment duration. When the treatment duration was longer than
      120 s, the fiber surface contact angle decreased from 90 degrees  to 43 degrees .
      The DBD plasma treatment resulted in a decrease in the tensile strength of the
      POM fiber, but the increase in the amount of -COH and -COOH on the surface of the
      POM fiber and the increase in the roughness resulted in an increase in the fiber
      pull-out bonding strength in cement from 2.15 N to 4.68 N.

PMID- 30275392
TI  - Acute Kidney Injury in Pregnancy: The Need for Higher Awareness. A Pragmatic
      Review Focused on What Could Be Improved in the Prevention and Care of Pregnancy
      Related AKI, in the Year Dedicated to Women and Kidney Diseases.
AB  - Pregnancy-related acute kidney injury (pAKI), preeclampsia (PE), and the
      hypertensive disorders of pregnancy are closely related conditions, which are, in
      turn, frequently linked to pre-existing and often non-diagnosed chronic kidney
      disease (CKD). The current literature and research mainly underline the effects
      of pregnancy complications on the offspring; this review strongly emphasizes the
      maternal health as well. These conditions not only negatively affect pregnancy
      outcomes, but have a relevant effect on the future health of affected mothers and
      their children. Therefore, dedicated diagnostic and follow-up programs are
      needed, for optimizing materno-foetal health and reducing the impact of pregnancy
      related problems in the mothers and in the new generations. This narrative
      review, performed on the occasion of the 2018 World Kidney Day dedicated to
      women's health, focuses on three aspects of the problem. Firstly, the risk of AKI
      in the hypertensive disorders of pregnancy (the risk is the highest in developing
      countries; however PE is the main cause of pregnancy related AKI worldwide).
      Secondly, the effect of AKI and the hypertensive disorders of pregnancy on the
      development of CKD in the mother and offspring: long-term risks are increased;
      the entity and the trajectories are still unknown. Thirdly, the role of CKD in
      the pathogenesis of AKI and the hypertensive disorders of pregnancy: CKD is a
      major risk factor and the most important element in the differential diagnosis;
      pregnancy is a precious occasion for early diagnosis of CKD. Higher awareness on
      the importance of AKI in pregnancy is needed to improve short and long term
      outcomes in mothers and children.

PMID- 30275397
TI  - The Behavior of the Maize B Chromosome and Centromere.
AB  - The maize B chromosome is a non-essential chromosome with an accumulation
      mechanism. The dispensable nature of the B chromosome facilitates many types of
      genetic studies in maize. Maize lines with B chromosomes have been widely used in
      studies of centromere functions. Here, we discuss the maize B chromosome
      alongside the latest progress of B centromere activities, including centromere
      misdivision, inactivation, reactivation, and de novo centromere formation. The
      meiotic features of the B centromere, related to mini-chromosomes and the control
      of the size of the maize centromere, are also discussed.

PMID- 30275398
TI  - A Combined Dietary and Cognitive Intervention in 3-5-Year-Old Children in
      Indonesia: A Randomized Controlled Trial.
AB  - Early childhood nutritional interventions typically combine nutritional and
      psychosocial stimulation. Such combined interventions result in long-lasting
      improvements of cognitive abilities in children who are malnourished. Here, we
      investigated potential cognitive abilities in normally developing children in
      Indonesia who were, however, at risk for suboptimal cognitive development due to
      little psychosocial stimulation in their home environment. In a randomized
      controlled intervention, children of the experimental group received nutritional
      supplementation combined with cognitive stimulation. Pre- and post-intervention
      measurements included cognitive development and functioning, behavior, and mother
      child interaction. The experimental and control group received nutritional
      supplementation in the form of a fortified or unfortified milk powder,
      respectively. Additionally, the children and parents of the experimental group
      jointly engaged in daily learning activities at home and performed iPad-based
      tasks designed to foster cognitive abilities. The experimental group compared to
      the control group displayed a significantly higher increase in intelligence
      quotient as well as a significantly larger reduction in attentional problems
      after the intervention. These results indicate that low-level cognitive
      stimulation in combination with nutritional supplementation during early
      childhood can be an effective intervention that improves global cognitive
      functioning in healthy developing children. ClinicalTrials.gov Identifier:
      NCT02359669.

PMID- 30275400
TI  - Testing of Automated Photochemical Reflectance Index Sensors as Proxy
      Measurements of Light Use Efficiency in an Aspen Forest.
AB  - Commercially available autonomous photochemical reflectance index (PRI) sensors
      are a new development in the remote sensing field that offer novel opportunities
      for a deeper exploration of vegetation physiology dynamics. In this study, we
      evaluated the reliability of autonomous PRI sensors (SRS-PRI) developed by METER
      Group Inc. as proxies of light use efficiency (LUE) in an aspen (Populus
      tremuloides) forest stand. Before comparisons between PRI and LUE measurements
      were made, the optical SRS-PRI sensor pairs required calibrations to resolve
      diurnal and seasonal patterns properly. An offline diurnal calibration procedure
      was shown to account for variable sky conditions and diurnal illumination changes
      affecting sensor response. Eddy covariance measurements provided seasonal gross
      primary productivity (GPP) measures as well as apparent canopy quantum yield
      dynamics (alpha). LUE was derived from the ratio of GPP to absorbed
      photosynthetically active radiation (APAR). Corrected PRI values were derived
      after diurnal and midday cross-calibration of the sensor's 532 nm and 570 nm fore
      optics, and closely related to both LUE (R2 = 0.62, p < 0.05) and alpha (R2 =
      0.72, p < 0.05). A LUE model derived from corrected PRI values showed good
      correlation to measured GPP (R2 = 0.77, p < 0.05), with an accuracy comparable to
      results obtained from an alpha driven LUE model (R2 = 0.79, p < 0.05). The
      automated PRI sensors proved to be suitable proxies of light use efficiency. The
      onset of continuous PRI sensors signifies new opportunities for explicitly
      examining the cause of changing PRI, LUE, and productivity over time and space.
      As such, this technology represents great value for the flux, remote sensing and
      modeling community.

PMID- 30275401
TI  - aP2-Cre Mediated Ablation of GHS-R Attenuates Adiposity and Improves Insulin
      Sensitivity during Aging.
AB  - Ghrelin via its receptor, the growth hormone secretagogue receptor (GHS-R),
      increases food intake and adiposity. The tissue-specific functions of GHS-R in
      peripheral tissues are mostly unknown. We previously reported that while GHS-R
      expression is very low in white and brown fat of young mice, expression increases
      during aging. To investigate whether GHS-R has cell-autonomous effects in adipose
      tissues, we generated aP2-Cre-mediated GHS-R knockdown mice (aP2-Cre/Ghsrf/f). We
      studied young (5-6 months) and old (15-17 months) aP2-Cre/Ghsrf/f mice and their
      age-matched controls. Interestingly, young aP2-Cre/Ghsrf/f mice had normal body
      weight but reduced fat; old mice showed pronounced reductions of both body weight
      and body fat. Calorimetry analysis revealed that aP2-Cre/Ghsrf/f mice had normal
      food intake and locomotor activity at both young and old age; but intriguingly,
      while energy expenditure was normal at young age, it was significantly increased
      at old age. Both young and old aP2-Cre/Ghsrf/f mice exhibited improved insulin
      sensitivity and glucose tolerance. Importantly, old aP2-Cre/Ghsrf/f mice
      maintained higher core body temperature at 4  degrees C, and showed higher
      expression of the thermogenic uncoupling protein 1 (UCP1) gene. The ex vivo
      studies further demonstrated that GHS-R deficient white adipocytes from old mice
      exhibit increased glucose uptake and lipolysis, promoting lipid mobilization.
      Despite the fact that the in vivo phenotypes of aP2-Cre/Ghsrf/f mice may not be
      exclusively determined by GHS-R knockdown in adipose tissues, our data support
      that GHS-R has cell-autonomous effects in adipocytes. The anabolic effect of GHS
      R in adipocytes is more pronounced in aging, which likely contributes to age
      associated obesity and insulin resistance.

PMID- 30275403
TI  - Influence of Roughness on Shear Bonding Performance of CFRP-Concrete Interface.
AB  - The potential of Fiber Reinforced Polymer (FRP) in the reinforcement of concrete
      structures has been shown in many studies and practical applications. However,
      few works have focused systematically on the development of quantitative criteria
      to measure surface roughness and relate this parameter to the bonding mechanical
      property. Moreover, some researchers have declared that, if the concrete
      interface is rougher, the bond performance between FRP and concrete will be
      increase, However, there is no answer to how rough the surface is. There are
      limited application standards for engineers to conduct in FRP reinforcement
      projects. This work evaluated several concrete specimens with three different
      strengths and six types of interface roughness. A single shear test was conducted
      to study the influence of surface roughness on the interfacial bonding
      performance of a carbon fiber-reinforced composite (CFRP)-concrete beam. The
      results show that, among the six interfaces, a concrete interface with the
      roughness of 0.44 has the best interfacial bonding performance. An interfacial
      appearance with the cement mortar almost cleaned away, and almost one fifth of
      the single coarse aggregate bared will get the best bond performance. Roughness
      parameters significantly influenced the effective bond length. The effective bond
      length of the six interfaces experienced an overall decreasing trend as the
      roughness increased. The bond-slip curves of concrete interfaces with roughness
      of 0.25-0.44 did not significantly change the rigidity within the brittle region.
      The rougher the interface was, the shorter the brittle region was. After entering
      a plasticity stage, the bond-slip curves for the six types of interfaces all
      declined with different slopes, and the max slip values were 0.04-0.35 mm when
      debonding failure occurred.

PMID- 30275399
TI  - Exploration of Survival Traits, Probiotic Determinants, Host Interactions, and
      Functional Evolution of Bifidobacterial Genomes Using Comparative Genomics.
AB  - Members of the genus Bifidobacterium are found in a wide-range of habitats and
      are used as important probiotics. Thus, exploration of their functional traits at
      the genus level is of utmost significance. Besides, this genus has been
      demonstrated to exhibit an open pan-genome based on the limited number of genomes
      used in earlier studies. However, the number of genomes is a crucial factor for
      pan-genome calculations. We have analyzed the pan-genome of a comparatively
      larger dataset of 215 members of the genus Bifidobacterium belonging to different
      habitats, which revealed an open nature. The pan-genome for the 56 probiotic and
      human-gut strains of this genus, was also found to be open. The accessory- and
      unique-components of this pan-genome were found to be under the operation of
      Darwinian selection pressure. Further, their genome-size variation was predicted
      to be attributed to the abundance of certain functions carried by genomic
      islands, which are facilitated by insertion elements and prophages. In silico
      functional and host-microbe interaction analyses of their core-genome revealed
      significant genomic factors for niche-specific adaptations and probiotic traits.
      The core survival traits include stress tolerance, biofilm formation, nutrient
      transport, and Sec-secretion system, whereas the core probiotic traits are
      imparted by the factors involved in carbohydrate- and protein-metabolism and host
      immunomodulations.

PMID- 30275402
TI  - Inflammation and the Gut-Liver Axis in the Pathophysiology of Cholangiopathies.
AB  - Cholangiocytes, the epithelial cells lining the bile ducts, represent the unique
      target of a group of progressive diseases known as cholangiopathies whose
      pathogenesis remain largely unknown. In normal conditions, cholangiocytes are
      quiescent and participate to the final bile volume and composition. Following
      exogenous or endogenous stimuli, cholangiocytes undergo extensive modifications
      of their phenotype. Reactive cholangiocytes actively proliferate and release a
      set of proinflammatory molecules, which act in autocrine/paracrine manner
      mediating the cross-talk with other liver cell types and innate and adaptive
      immune cells. Cholangiocytes themselves activate innate immune responses against
      gut-derived microorganisms or bacterial products that reach the liver via
      enterohepatic circulation. Gut microbiota has been implicated in the development
      and progression of the two most common cholangiopathies, i.e., primary sclerosing
      cholangitis (PSC) and primary biliary cholangitis (PBC), which have distinctive
      microbiota composition compared to healthy individuals. The impairment of
      intestinal barrier functions or gut dysbiosis expose cholangiocytes to an
      increasing amount of microorganisms and may exacerbate inflammatory responses
      thus leading to fibrotic remodeling of the organ. The present review focuses on
      the complex interactions between the activation of innate immune responses in
      reactive cholangiocytes, dysbiosis, and gut permeability to bacterial products in
      the pathogenesis of PSC and PBC.

PMID- 30275405
TI  - High Throughput Manufacturing of Bacteriophages Using Continuous Stirred Tank
      Bioreactors Connected in Series to Ensure Optimum Host Bacteria Physiology for
      Phage Production.
AB  - Future industrial demand for large quantities of bacteriophages e.g., for phage
      therapy, necessitates the development of scalable Good Manufacturing Practice
      compliant (cGMP) production platforms. The continuous production of high titres
      of E coli T3 phages (1011 PFU mL-1) was achieved using two continuous stirred
      tank bioreactors connected in series, and a third bioreactor was used as a final
      holding tank operated in semi-batch mode to finish the infection process. The
      first bioreactor allowed the steady-state propagation of host bacteria using a
      fully synthetic medium with glucose as the limiting substrate. Host bacterial
      growth was decoupled from the phage production reactor downstream of it to
      suppress the production of phage-resistant mutants, thereby allowing stable
      operation over a period of several days. The novelty of this process is that the
      manipulation of the host reactor dilution rates (range 0.1-0.6 hr-1) allows
      control over the physiological state of the bacterial population. This results in
      bacteria with considerably higher intracellular phage production capability
      whilst operating at high dilution rates yielding significantly higher overall
      phage process productivity. Using a pilot-scale chemostat system allowed
      optimisation of the upstream phage amplification conditions conducive for high
      intracellular phage production in the host bacteria. The effect of the host
      reactor dilution rates on the phage burst size, lag time, and adsorption rate
      were evaluated. The host bacterium physiology was found to influence phage burst
      size, thereby affecting the productivity of the overall process. Mathematical
      modelling of the dynamics of the process allowed parameter sensitivity evaluation
      and provided valuable insights into the factors affecting the phage production
      process. The approach presented here may be used at an industrial scale to
      significantly improve process control, increase productivity via process
      intensification, and reduce process manufacturing costs through process footprint
      reduction.

PMID- 30275404
TI  - Biological and Chemical Diversity of Ascidian-Associated Microorganisms.
AB  - Ascidians are a class of sessile filter-feeding invertebrates, that provide
      unique and fertile niches harboring various microorganisms, such as bacteria,
      actinobacteria, cyanobacteria and fungi. Over 1000 natural products, including
      alkaloids, cyclic peptides, and polyketides, have been isolated from them, which
      display diverse properties, such as antibacterial, antifungal, antitumor, and
      anti-inflammatory activities. Strikingly, direct evidence has confirmed that ~8%
      of natural products from ascidians are actually produced by symbiotic
      microorganisms. In this review, we present 150 natural products from
      microorganisms associated with ascidians that have been reported up to 2017.

PMID- 30275407
TI  - Micro-Doppler Feature Extraction of Inverse Synthetic Aperture Imaging Laser
      Radar Using Singular-Spectrum Analysis.
AB  - Different from microwave radar, laser radar could be more sensitive to the micro
      Doppler (m-D) effect due to its wave length. This limits the application of
      conventional methods, such as time-frequency based approach, since the processing
      needs a receiver with much higher sampling frequency than microwave radar. In
      this paper, a micro-Doppler feature extraction algorithm is proposed for the
      inverse synthetic aperture imaging laser radar (ISAIL). Singular-spectrum
      analysis (SSA) is employed for separation and reconstruction of the micro-Doppler
      and rigid body signal. Clear ISAIL image is obtained by minimum entropy criteria
      after echo signal decomposition. After theoretical derivation, the computation
      efficiency and ability of the proposed method is proved by the results of
      simulation and real data of An-26.

PMID- 30275406
TI  - Meroterpenoids and Isocoumarinoids from a Myrothecium Fungus Associated with
      Apocynum Venetum.
AB  - Four new meroterpenoids 1-4 and four new isocoumarinoids 5-8, along with five
      known isocoumarinoids (9-13), were isolated from the fungus Myrothecium sp.
      OUCMDZ-2784 associated with the salt-resistant medicinal plant, Apocynum venetum
      (Apocynaceae). Their structures were elucidated by means of spectroscopic
      analysis, X-ray crystallography, ECD spectra and quantum chemical calculations.
      Compounds 1-5, 7, 9 and 10 showed weak alpha-glucosidase inhibition with the IC50
      values of 0.50, 0.66, 0.058, 0.20, 0.32, 0.036, 0.026 and 0.37 mM, respectively.

PMID- 30275409
TI  - The Implementation Process for Pharmacogenomic Testing for Cancer-Targeted
      Therapies.
AB  - Recent advances in genomic medicine have led to the availability of genomic tests
      that have the potential to improve population health, yet the process for
      obtaining these tests and getting them reimbursed by insurers has not been
      described. The objective of this study was to describe the process of ordering
      pharmacogenomic tests by interviewing providers, patients, and laboratories about
      cancer-related pharmacogenomic tests. We interviewed patients who were
      prescribed, providers who prescribed medications that should be guided by
      pharmacogenomic testing, and individuals from diagnostic laboratories. A total of
      10 providers, 16 patients, and eight diagnostic laboratories described logistical
      and insurance issues relating to ordering and receiving pharmacogenomic tests and
      medications. We found that the process of ordering pharmacogenomic tests is time
      consuming, expensive, and complex. Ordering pharmacogenomic tests is quite
      different across institutions. Even in the same institution, multiple providers
      can order the test. Once the provider places the order for the pharmacogenomic
      test, the laboratory receives the request and usually begins testing without
      knowing how the test will be paid for. Next, the laboratory completes the
      pharmacogenomic testing and the results of the tests are reported to providers,
      patients, or placed directly in the medical record. In conclusion, processes
      related to ordering and obtaining insurance coverage for pharmacogenomic tests
      varies greatly across institutions and is time-consuming.

PMID- 30275411
TI  - 40 Years of Percutaneous Coronary Intervention: History and Future Directions.
AB  - The field of interventional cardiology has evolved significantly since the first
      percutaneous transluminal coronary angioplasty was performed 40 years ago. This
      evolution began with a balloon catheter mounted on a fixed wire and has
      progressed into bare-metal stents (BMS), first-generation drug-eluting stents
      (DES), second- and third-generation biodegradable polymer-based DES, and
      culminates with the advent of bioabsorbable stents, which are currently under
      development. Each step in technological advancement has improved outcomes, while
      new persisting challenges arise, caused by the stent scaffolds, the polymers
      employed, and the non-selective cytostatic and cytotoxic drugs eluted from the
      stents. Despite the promising technological advances made in stent technology,
      managing the balance between reductions in target lesion revascularization, stent
      thrombosis, and bleeding remain highly complex issues. This review summarizes the
      evolution of percutaneous coronary intervention with a focus on vascular
      dysfunction triggered by the non-selective drugs eluted from various stents. It
      also provides an overview of the mechanism of action of the drugs currently used
      in DES. We also discuss the efforts made in developing novel cell-selective drugs
      capable of inhibiting vascular smooth muscle cell (VSMC) proliferation,
      migration, and infiltration of inflammatory cells while allowing for complete
      reendothelialization. Lastly, in the era of precision medicine, considerations of
      patients' genetic variance associated with myocardial infarction and in-stent
      restenosis are discussed. The combination of personalized medicine and improved
      stent platform with cell-selective drugs has the potential to solve the remaining
      challenges and improve the care of coronary artery disease patients.

PMID- 30275410
TI  - Association of Uremic Toxins and Inflammatory Markers with Physical Performance
      in Dialysis Patients.
AB  - Association of higher serum levels of uremic toxins and inflammatory markers with
      poorer physical performance is understudied. We measured the six-minute walk test
      (6MWT), 10 repetition sit-to-stand test (STS-10), handgrip strength (HGS), and
      Human Activity Profile (HAP) questionnaire score in 90 prevalent hemodialysis
      patents, with low comorbidity to reduce the potential confounding of concomitant
      disease. Midweek pre-dialysis serum levels of asymmetric dimethyl-arginine
      (ADMA), beta2-microglobulin (B2M), high-sensitivity C-reactive protein (hs-CRP),
      indoxyl sulfate (IS), insulin-like growth factor 1 (IGF-1), interleukin 6 (IL-6),
      myostatin, and urea were analyzed as predictor parameters of physical performance
      measures in adjusted models. Serum levels of most measured toxins were not
      significantly related to performance, except for ADMA, which was significantly
      related to poorer performance in the STS-10 test (B = 0.11 +/- 0.03 s, p < 0.01).
      Higher hs-CRP was associated with poorer results in the 6MWT (B = -2.6 +/- 0.97
      m, p < 0.01) and a lower HAP score (B = -0.36 +/- 0.14, p = 0.01). There were no
      other significant associations found. We conclude that inflammation may be a more
      important pathway to physical impediment than uremic toxemia. This suggests that
      there is a large physical rehabilitation potential in non-inflamed uremic
      patients.

PMID- 30275408
TI  - Roles of Mitogen-Activated Protein Kinases in Osteoclast Biology.
AB  - Bone undergoes continuous remodeling, which is homeostatically regulated by
      concerted communication between bone-forming osteoblasts and bone-degrading
      osteoclasts. Multinucleated giant osteoclasts are the only specialized cells that
      degrade or resorb the organic and inorganic bone components. They secrete
      proteases (e.g., cathepsin K) that degrade the organic collagenous matrix and
      establish localized acidosis at the bone-resorbing site through proton-pumping to
      facilitate the dissolution of inorganic mineral. Osteoporosis, the most common
      bone disease, is caused by excessive bone resorption, highlighting the crucial
      role of osteoclasts in intact bone remodeling. Signaling mediated by mitogen
      activated protein kinases (MAPKs), including extracellular signal-regulated
      kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, has been recognized to be
      critical for normal osteoclast differentiation and activation. Various exogenous
      (e.g., toll-like receptor agonists) and endogenous (e.g., growth factors and
      inflammatory cytokines) stimuli contribute to determining whether MAPKs
      positively or negatively regulate osteoclast adhesion, migration, fusion and
      survival, and osteoclastic bone resorption. In this review, we delineate the
      unique roles of MAPKs in osteoclast metabolism and provide an overview of the
      upstream regulators that activate or inhibit MAPKs and their downstream targets.
      Furthermore, we discuss the current knowledge about the differential kinetics of
      ERK, JNK, and p38, and the crosstalk between MAPKs in osteoclast metabolism.

PMID- 30275412
TI  - Healthcare Utilization in a Large Cohort of Asylum Seekers Entering Western
      Europe in 2015.
AB  - During the current period of immigration to Western Europe, national healthcare
      systems are confronted with high numbers of asylum seekers with largely unknown
      health status. To improve care taking strategies, we assessed healthcare
      utilization in a large, representative cohort of newly arriving migrants
      consisting of n = 1533 residents of a reception center in Northern Germany in
      2015. Most asylum seekers were young, male adults, and the majority came from the
      Eastern Mediterranean region. Overall, we observed a frequency of 0.03 visits to
      the onsite primary healthcare ward per asylum seeker and day of camp residence
      (IQR 0.0-0.07, median duration of residence 38.0 days, IQR 30.0-54.25). Female
      asylum seekers showed higher healthcare utilization rates than their male
      counterparts, and healthcare utilization was particularly low in asylum seekers
      in their second decade of life. Furthermore, a significant correlation between
      time after camp entrance and healthcare utilization behavior occurred: During the
      first week of camp residence, 37.1 visits/100 asylum seekers were observed,
      opposed to only 9.5 visits/100 asylum seekers during the sixth week of camp
      residence. This first data on healthcare utilization in a large, representative
      asylum seeker cohort entering Western Europe during the current crisis shows that
      primary care is most needed in the first period directly after arrival. Our
      dataset may help to raise awareness for refugee and migrant healthcare needs and
      to adapt care taking strategies accordingly.

PMID- 30275413
TI  - Kinetics of the Solution-Mediated Polymorphic Transformation of the Novel l
      Carnitine Orotate Polymorph, Form-II.
AB  - Research studies related to the polymorphs of l-Carnitine orotate (CO), a
      medication used for the treatment and prevention of liver diseases, are
      insignificant or almost nonexistent. Accordingly, in the present study, l
      Carnitine orotate (CO) was prepared for investigating CO polymorphs. Here, a
      reactive crystallization was induced by reacting 1g of l-Carn (1 equivalent) and
      0.97 g of OA (1 equivalent) in methanol (MeOH); as a result, CO form-I and CO
      form-II polymorphs were obtained after 1 h and 16 h of stirring, respectively.
      The characterization of CO polymorphs was carried out utilizing Powder X-ray
      diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric
      Analysis (TGA) and solid-state Nuclear Magnetic Resonance Spectroscopy (solid
      state CP/MAS 13C-NMR). The solution-mediated polymorphic transformation (SMPT) of
      CO polymorphs was investigated in MeOH at controlled temperature and fixed
      rotational speed. The results revealed that CO form-I is a metastable polymorph
      while CO form-II is a stable polymorph. From the same results, it was confirmed
      that CO form-I was converted to CO form-II during the polymorphic phase
      transformation process. Moreover, it was assessed that the increase in
      temperature and supersaturation level significantly promotes the rate of
      nucleation, as well as the rate of mass transfer of CO form-II. In addition,
      nucleation and mass transfer equations were employed for the quantitative
      determination of SMPT experimental results. Lastly, it was suggested that CO form
      II was more thermodynamically stable than CO form-I and that both polymorphs
      belong to the monotropic system.

PMID- 30275415
TI  - Effects of Amorphous Calcium Phosphate Administration on Dental Sensitivity
      during In-Office and At-Home Interventions.
AB  - BACKGROUND: Tooth bleaching is the most frequently employed whitening procedure
      in clinics. The major side effect of tooth bleaching is dental sensitivity during
      and after the treatment. Here, we evaluated whether the administration of
      amorphous calcium phosphate (ACP), during in-office and at-home procedures may
      impact on dental sensitivity. METHODS: Eighty patients, responding to the study
      requirements were enrolled according to the following criteria. Group 1 (n = 40),
      received in-office, 10% ACP prior to 30% professional hydrogen peroxide
      application. The whitening procedure continued at home using 10% carbamide
      peroxide with 15% ACP for 15 days. Group 2 (n = 40) received only 30% hydrogen
      peroxide application and continued the whitening procedures at home, using 10%
      carbamide hydroxide, without ACP- Casein phosphopeptides (CPP), for 15 days.
      Dental sensitivity was recorded with a visual analogue scale (VAS) at baseline,
      immediately after, and at 15 days after treatment in the two groups. RESULTS: We
      observed that patients receiving ACP in the bleaching mixture experienced
      decreased dental sensitivity (* p <= 0.05), as detected by VAS scale analysis
      immediately following the procedures. Patients receiving ACP-CPP during at-home
      procedures showed a statistically significant (*** p <= 0.0001) reduction of
      dental sensitivity. CONCLUSIONS: We demonstrated that ACP-CPP administration,
      while exerting the same whitening effects as in control subjects receiving
      potassium fluoride (PF), had an impact on the reduction of dental sensitivity,
      improving patient compliance.

PMID- 30275414
TI  - Converting Galactose into the Rare Sugar Talose with Cellobiose 2-Epimerase as
      Biocatalyst.
AB  - Cellobiose 2-epimerase from Rhodothermus marinus (RmCE) reversibly converts a
      glucose residue to a mannose residue at the reducing end of beta-1,4-linked
      oligosaccharides. In this study, the monosaccharide specificity of RmCE has been
      mapped and the synthesis of d-talose from d-galactose was discovered, a reaction
      not yet known to occur in nature. Moreover, the conversion is industrially
      relevant, as talose and its derivatives have been reported to possess important
      antimicrobial and anti-inflammatory properties. As the enzyme also catalyzes the
      keto-aldo isomerization of galactose to tagatose as a minor side reaction, the
      purity of talose was found to decrease over time. After process optimization, 23
      g/L of talose could be obtained with a product purity of 86% and a yield of 8.5%
      (starting from 4 g (24 mmol) of galactose). However, higher purities and
      concentrations can be reached by decreasing and increasing the reaction time,
      respectively. In addition, two engineering attempts have also been performed.
      First, a mutant library of RmCE was created to try and increase the activity on
      monosaccharide substrates. Next, two residues from RmCE were introduced in the
      cellobiose 2-epimerase from Caldicellulosiruptor saccharolyticus (CsCE)
      (S99M/Q371F), increasing the kcat twofold.

PMID- 30275416
TI  - Knowledge, Attitudes, and Practices of Mothers of Preschool Children About Oral
      Health in Qatar: A Cross-Sectional Survey.
AB  - Health-related behaviors are influenced by knowledge and awareness, with oral
      health being no exception. It is well-known that oral diseases are influenced by
      social determinants. There is an association between the oral health knowledge of
      mothers and the status of their children's oral health. In Qatar, the knowledge
      and practices of oral health in preschool children have not been previously
      reported. The aim of this study was to assess the knowledge, attitude, and
      related practices of mothers of preschool children about oral health in Qatar. A
      total of 400 questionnaires were distributed by the principals of kindergarten to
      mothers of children attending 16 government kindergartens in Qatar. The
      questionnaire included 38 close-ended questions grouped into nine categories,
      addressing different aspects of knowledge and practices related to early
      childhood oral health. The questionnaire was constructed in English, before being
      translated into Arabic, which is the local language in Qatar. The questionnaire
      instrument was pre-tested on mothers with demographic characteristics matching
      the main population. These participants were not included in the main study. The
      questionnaire study was associated with a clinical epidemiological study to
      assess dental caries and enamel defects of the sampled children. The dmft caries
      index (decayed, missing and filled teeth) was used for that purpose according to
      the World Health Organization criteria. For the questionnaire administered to
      mothers with clinical survey variables, a binary logistic regression analysis was
      performed to determine the associations between the measures of oral health
      status (dmft, Dental index) and mothers' oral health knowledge and practices. A
      total of 48% mothers thought that children should have their teeth brushed from
      the age of three years and 42% chose younger than two years as a starting age for
      brushing. More than half (54%) of the mothers thought that children should not
      have their teeth flossed. In general, no significant statistical association was
      found between dmft and any other variables, except for whether or not the child
      had visited the dentist. Logistic regression analyses were performed to determine
      the association between the measures of oral health status (dmft, DI) and
      mothers' oral health knowledge and practices. After controlling for the other
      independent variables included in this model, the test of the model was not
      statistically significant, which indicated that none of the variables represent a
      significant risk for occurrence of caries. The only exception was whether or not
      the child had visited the dentist (odds ratio = 2.51, 95% confidence interval
      1.091-5.774). Despite the existence of good knowledge of oral health care, there
      were deficiencies in the oral health care provided to children. This may reflect
      that seeking dental care is either not very important or it is challenging to
      obtain access to a child-friendly dentist in the public health system in Qatar.
      The results of this study suggest that there is a need for an oral health
      promotion program to fill the gaps in knowledge for mothers regarding oral health
      care for young children.

PMID- 30275417
TI  - Characterization of the Piezoresistive Effects of Silicon Nanowires.
AB  - Silicon nanowires (SiNWs) have received attention in recent years due to their
      anomalous piezoresistive (PZR) effects. Although the PZR effects of SiNWs have
      been extensively researched, they are still not fully understood. Herein, we
      develop a new model of the PZR effects of SiNWs to characterize the PZR effects.
      First, the resistance of SiNW is modeled based on the surface charge density. The
      characteristics of SiNW, such as surface charge and effective conducting area,
      can be estimated by using this resistance model. Then, PZR effects are modeled
      based on stress concentration and piezopinch effects. Stress concentration as a
      function of the physical geometry of SiNWs can amplify PZR effects by an order of
      magnitude. The piezopinch effects can also result in increased PZR effects that
      are at least two times greater than that of bulk silicon. Experimental results
      show that the proposed model can predict the PZR effects of SiNWs accurately.

PMID- 30275418
TI  - The Association between Vitamin D Deficiency and Sleep Disorders: A Systematic
      Review and Meta-Analysis.
AB  - Epidemiology studies have investigated the association between vitamin D and the
      risk of sleep disorders, but the results remain controversial. Therefore, we
      conducted this meta-analysis with the goal of clarifying the association between
      vitamin D and sleep disorders risk. All relevant studies were searched using
      PubMed, EMBASE, and Web of Science from inception to January 2018. Pooled odds
      ratios (ORs) and 95% confidence interval (CIs) were calculated using a fixed
      effect model A total of nine studies (6 cross-sectional, 2 case-control, and 1
      cohort studies) involving 9397 participants were included. By comparing the
      lowest verse highest levels of serum vitamin D, we found that participants with
      vitamin D deficiency (VDD) had a significantly increased risk of sleep disorders
      (OR: 1.50, 95% CI: 1.31, 1.72). Subgroup analysis showed that VDD also was
      associated with poor sleep quality (OR: 1.59, 95% CI: 1.23, 2.05), short sleep
      duration (OR: 1.74, 95% CI: 1.30, 2.32), and sleepiness (OR: 1.36, 95% CI: 1.12,
      1.65). Subgroup analyses further indicated that serum 25(OH)D <20 ng/mL could
      significantly increase the risk of unhealthy sleep. This meta-analysis suggest
      that vitamin D deficiency is associated with a higher risk of sleep disorders.
      More high-quality cohort studies and randomized controlled trials (RCTs) are
      needed to verify this association.

PMID- 30275419
TI  - What is the Validity of Questionnaires Assessing Fruit and Vegetable Consumption
      in Children when Compared with Blood Biomarkers? A Meta-Analysis.
AB  - Fruit and vegetable consumption has been associated with improved health outcomes
      in children. As an extensive number of questionnaires are currently used to
      assess fruit and vegetable consumption, we performed a systematic review of the
      criterion validity of questionnaires used to estimate fruit and vegetable
      consumption in children, considering blood biomarkers as the reference method.
      Five electronic databases (MEDLINE, CINAHL, Scopus, PsycINFO, Web of Science)
      were searched from database inception to 23 July 2018. The search strategy used
      the following sets of descriptors: children; fruits and vegetables; dietary
      questionnaires; blood biomarkers; and validation coefficient. The search terms
      were adapted for use with other databases in combination with database-specific
      filters. Potentially eligible articles were selected independently by two
      reviewers, separately, following the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) guidelines. Two articles meeting the inclusion
      criteria were included. The main reason for study exclusion was the sample age
      range, which included adolescents. The pooled correlation coefficient was 0.32
      (95% confidence interval: 0.24-0.40).This review provided insights into
      assessment methods of fruit and vegetable consumption in children. Although
      further studies are required, questionnaires for assessing fruit and vegetable
      consumption have fair criterion validity in children.

PMID- 30275420
TI  - Purification and Identification of Angiotensin I-Converting Enzyme Inhibitory
      Peptides and the Antihypertensive Effect of Chlorella sorokiniana Protein
      Hydrolysates.
AB  - Hot water was used to obtain Chlorella sorokiniana hot water extract (HWE).
      Subsequently, this byproduct was freeze-dried, hydrolysed at 50  degrees C using
      Protease N to obtain C. sorokiniana protein hydrolysates (PN-1), and then
      digested with a gastrointestinal enzyme (PN-1G). The inhibitory effects of the
      HWE and hydrolysates against angiotensin I-converting enzyme (ACE) were
      investigated. The soluble protein and peptide contents were 379.9 and 179.7 mg/g,
      respectively, for HWE and 574.8 and 332.8 mg/g, respectively, for PN-1. The IC50
      values of the HWE, PN-1, and PN-1G on ACE were 1.070, 0.035, and 0.044 mg/mL,
      respectively. PN-1G was separated into seven fractions through size exclusion
      chromatography. The sixth fraction of the hydrolysate had a molecular weight
      between 270 and 340 Da, and the lowest IC50 value on ACE was 0.015 mg/mL. The
      amino acid sequences of the ACE-inhibitory peptides were Trp-Val, Val-Trp, Ile
      Trp, and Leu-Trp, of which the IC50 values were 307.61, 0.58, 0.50, and 1.11 uMU,
      respectively. Systolic blood pressure and diastolic blood pressure were reduced
      20 and 21 mm Hg, respectively, in spontaneously hypertensive rats after 6 h of
      oral administration with a dose of 171.4 mg PN-1 powder/kg body weight.

PMID- 30275421
TI  - How Eliminating Malaria May Also Prevent Iron Deficiency in African Children.
AB  - Malaria and iron deficiency are common among children living in sub-Saharan
      Africa. Several studies have linked a child's iron status to their future risk of
      malaria infection; however, few have examined whether malaria might be a cause of
      iron deficiency. Approximately a quarter of African children at any one time are
      infected by malaria and malaria increases hepcidin and tumor necrosis factor
      alpha concentrations leading to poor iron absorption and recycling. In support of
      a hypothetical link between malaria and iron deficiency, studies indicate that
      the prevalence of iron deficiency in children increases over a malaria season and
      decreases when malaria transmission is interrupted. The link between malaria and
      iron deficiency can be tested through the use of observational studies,
      randomized controlled trials and genetic epidemiology studies, each of which has
      its own strengths and limitations. Confirming the existence of a causal link
      between malaria infection and iron deficiency would readjust priorities for
      programs to prevent and treat iron deficiency and would demonstrate a further
      benefit of malaria control.

PMID- 30275423
TI  - Effects of Inoculation on the Pearlitic Gray Cast Iron with High Thermal
      Conductivity and Tensile Strength.
AB  - With the aim of improving the thermal conductivity and tensile strength of
      pearlitic gray cast iron, the influence of inoculation on structure and
      properties was experimentally investigated. Three group of irons with similar
      compositions were inoculated by Zr-FeSi, Sr-FeSi, and SiC inoculants,
      respectively. The metallographic analysis was used to measure the maximum
      graphite length, primary dendrites amount and eutectic colonies counts. For a
      certain carbon equivalent, it was confirmed that the thermal conductivity of
      pearlitic gray cast iron has a direct correlation with the maximum graphite
      length while the tensile strength was influenced mainly by the primary dendrites
      amount. The optimal structure and highest thermal conductivity and tensile
      strength were obtained by Sr-FeSi inoculant. MnS particles act a pivotal part in
      modifying the structure of gray cast iron. It was found that providing nucleation
      sites both for graphite and primary austenite is important to promote the thermal
      conductivity and strength. However, excessive nuclei (MnS particles) results in
      shorter graphite flakes and thus the depressive growth of primary dendrites.

PMID- 30275422
TI  - Hepatoprotective Effect of Loquat Leaf Flavonoids in PM2.5-Induced Non-Alcoholic
      Fatty Liver Disease via Regulation of IRs-1/Akt and CYP2E1/JNK Pathways.
AB  - Ambient air particulate matter (PM) represents a class of heterogeneous
      substances present in polluted air, which contains many harmful components.
      Exposure to ambient particulate matter in fine rages (PM2.5) is associated with
      non-alcoholic fatty liver disease (NAFLD). Loquat Leaf possesses pharmacological
      actions on NAFLD. As the main biological active ingredients, the potential
      therapeutic role of total flavonoids (TF) isolated from Loquat Leaf in PM2.5
      induced NAFLD model remains unclear. The present study was designed to explore
      the hepatoprotective effect of TF in PM2.5-induced NAFLD mice with its related
      mechanisms of action. Mice were exposed to PM2.5 to induce NAFLD, and body
      weight, the ratio of liver to body weight, and blood lipids increased
      significantly compared with the control group. It was found that TF significantly
      reduced the above parameters in PM2.5-induced NAFLD mice. TF treatment alleviated
      oxidative stress by preventing the accumulation of oxidative product
      malondialdehyde (MDA) and by strengthening the anti-oxidative capacity of
      superoxide dismutase (SOD). TF was also found to reduce the alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) activity in the PM2.5
      group. In addition, TF repaired the PM2.5-induced decline of insulin receptor
      substrate-1 (IRs-1) and protein kinase B (Akt) phosphorylation. Meanwhile, the
      data showed TF suppressed the expression of cytochrome P450 2E1(CYP2E1) and the
      phosphorylation of c-jun N-terminal kinase (JNK) in PM2.5-induced NAFLD. Taken
      together, these findings show that TF alleviate PM2.5-induced NAFLD via
      regulation of IRs-1/Akt and CYP2E1/JNK pathways, which may have potential for
      further development as novel therapeutic agents for NAFLD.

PMID- 30275424
TI  - Developing Lignosulfonate-Based Activated Carbon Fibers.
AB  - In this study, electrospinning technology, physical activation, and carbonization
      processing were applied to produce lignosulfonate-based activated carbon fibers.
      The porous structure of the produced lignosulfonate-based activated carbon fibers
      primarily contained mesopores and a relatively small amount of micropores.
      Moreover, insufficient carbonization caused fiber damage during CO2 activation.
      The weight loss rate and specific surface area increased with increase in
      carbonization time, and products with carbonization temperatures of 700  degrees
      C were of higher quality than those with other temperatures. Moreover, the two
      step carbonization process provided fibers with improved quality because of a low
      weight loss rate, improved processing, and high surface area. Lignosulfonate
      based activated carbon fibers can be used as a highly efficient adsorption and
      filtration material, and further development of its applications would be
      valuable.

PMID- 30275425
TI  - Stable Logic Operation of Fiber-Based Single-Walled Carbon Nanotube Transistor
      Circuits Toward Thread-Like CMOS Circuitry.
AB  - A fiber-based single-walled carbon nanotube (SWCNT) thin-film-transistor (TFT)
      has been proposed. We designed complementary SWCNT TFT circuit based on SPICE
      simulations, with device parameters extracted from the fabricated fiber-based
      SWCNT TFTs, such as threshold voltage, contact resistance, and off-/gate-leakage
      current. We fabricated the SWCNTs CMOS inverter circuits using the selective
      passivation and n-doping processes on a fiber substrate. By comparing the
      simulation and experimental results, we could enhance the circuit's performance
      by tuning the threshold voltage between p-type and n-type TFTs, reducing the
      source/drain contact resistance and off current level, and maintaining a low
      output capacitance of the TFTs. Importantly, it was found that the voltage gain,
      output swing range, and frequency response of the fiber-based inverter circuits
      can be dramatically improved.

PMID- 30275426
TI  - Fabricating a Novel Intragranular Microstructure for Al2O3/GdAlO3 Ceramic
      Composites.
AB  - In order to make the embryonic form of intragranular structure, the Al2O3/GdAlO3
      system was selected due to its excellent mechanical properties. Gd2O3 and
      Al(NO3)3.9H2O were used as the starting materials. A co-precipitation method was
      used for the preparation of fine ceramics and applied to synthesize the nano
      powder of GdAlO3 firstly. Then, the nano-powder of GdAlO3 was mixed with the
      precipitates by the second co-precipitation method. After drying and calcination,
      the compound powder with eutectic composition (77 mol % Al3+-23 mol % Gd3+) was
      fast sintered by using the spark plasma sintering technique. The results revealed
      that the phases of the sintered samples were Al2O3 and GdAlO3. The phases showed
      a homogeneous and interlaced distribution. All the matrix grains were submicron.
      The sizes of the intragranular structures were between 50 nm and 150 nm.
      Therefore, the intragranular structure displayed a novel mixture of nanometer
      submicron and submicron-submicron types. The different intragranular structures
      all changed the fracture modes of Al2O3 grains from intergranular fracture to
      transgranular fracture.

PMID- 30275427
TI  - Encapsulation of Rat Bone Marrow Derived Mesenchymal Stem Cells in Alginate
      Dialdehyde/Gelatin Microbeads with and without Nanoscaled Bioactive Glass for In
      Vivo Bone Tissue Engineering.
AB  - Alginate dialdehyde (ADA), gelatin, and nano-scaled bioactive glass (nBG)
      particles are being currently investigated for their potential use as three
      dimensional scaffolding materials for bone tissue engineering. ADA and gelatin
      provide a three-dimensional scaffold with properties supporting cell adhesion and
      proliferation. Combined with nanocristalline BG, this composition closely mimics
      the mineral phase of bone. In the present study, rat bone marrow derived
      mesenchymal stem cells (MSCs), commonly used as an osteogenic cell source, were
      evaluated after encapsulation into ADA-gelatin hydrogel with and without nBG.
      High cell survival was found in vitro for up to 28 days with or without addition
      of nBG assessed by calcein staining, proving the cell-friendly encapsulation
      process. After subcutaneous implantation into rats, survival was assessed by
      DAPI/TUNEL fluorescence staining. Hematoxylin-eosin staining and
      immunohistochemical staining for the macrophage marker ED1 (CD68) and the
      endothelial cell marker lectin were used to evaluate immune reaction and
      vascularization. After in vivo implantation, high cell survival was found after 1
      week, with a notable decrease after 4 weeks. Immune reaction was very mild,
      proving the biocompatibility of the material. Angiogenesis in implanted
      constructs was significantly improved by cell encapsulation, compared to cell
      free beads, as the implanted MSCs were able to attract endothelial cells.
      Constructs with nBG showed higher numbers of vital MSCs and lectin positive
      endothelial cells, thus showing a higher degree of angiogenesis, although this
      difference was not significant. These results support the use of ADA/gelatin/nBG
      as a scaffold and of MSCs as a source of osteogenic cells for bone tissue
      engineering. Future studies should however improve long term cell survival and
      focus on differentiation potential of encapsulated cells in vivo.

PMID- 30275428
TI  - Effect of Arthrospira (Spirulina) maxima Supplementation and a Systematic
      Physical Exercise Program on the Body Composition and Cardiorespiratory Fitness
      of Overweight or Obese Subjects: A Double-Blind, Randomized, and Crossover
      Controlled Trial.
AB  - : Excess weight and obesity are major risk factors for many chronic diseases, and
      weight-loss interventions often include systematic exercise and nutritional
      supplements. The purpose of this study was to determine the
      independent/synergistic effects of Arthrospira (Spirulina) maxima supplementation
      (six weeks, 4.5 g.day-1) and a systematic physical exercise program (six weeks,
      twice weekly) on the body composition and cardiorespiratory fitness of overweight
      and obese subjects. To achieve this, 27 overweight and 25 obese sedentary male
      subjects were assigned to four interventions through a randomized double-blind,
      crossover controlled trial: A physical exercise program, with (SE) or without
      (Ex) Spirulina maxima; or no-exercise program, with (Sm) and without (C)
      Spirulina maxima. The body composition and cardiorespiratory fitness parameters
      were taken during a maximum intensity test. As compared to the C group, the body
      fat percentage of the SE, Sm and Ex groups was reduced (p < 0.05), while their
      maximal oxygen uptake improved (r = -0.40), and obese subjects benefited more
      significantly. Weight loss, the time to reach fatigue and the onset of blood
      lactate accumulation were improved in both of the Spirulina maxima supplemented
      groups, regardless of the subjects' body weight. Spirulina maxima supplementation
      synergistically improves the effects of systematic exercise on body composition
      and cardiorespiratory fitness parameters in overweight, but mostly in individuals
      with obesity. TRIAL REGISTRATION: Clinical Trials, NCT02837666. Registered 19
      July 2016.

PMID- 30275429
TI  - Preliminary Study to Determinate the Effect of the Rearing Managements Applied
      during Heifers' Whole Life on Carcass and Flank Steak Quality.
AB  - The aim of this study was to investigate the impact of rearing managements
      applied during a heifers' whole life on the carcass and flank steak (rectus
      abdominis) meat traits. For this study, rearing managements applied on 96 heifers
      were identified by conducting surveys in farms. A heifers' whole life was divided
      into three key periods: Pre-weaning, growth, and fattening. The combination of
      the rearing factors applied during the heifers' whole life allowed us to
      characterize several rearing managements. Among them, four have been studied in
      depth. The main results displayed that the carcass traits were more sensitive to
      the rearing managements than the flank steak traits. The different managements
      considered had an impact on the weight, the dressing percentage and the
      conformation score of the carcass. Whereas, they had no impact on the sensory
      descriptors, the sheer force and the color of the flank steak. This study showed
      that the variations observed for carcass and meat traits could not be explained
      by the variation of only one rearing factor but could be explained by many
      rearing factors characterizing the rearing management applied. Finally, this
      study demonstrated that it was possible to improve carcass traits without
      deteriorating meat traits.

PMID- 30275430
TI  - Enhancing Bioactive Antioxidants' Extraction from "Horchata de Chufa" By
      Products.
AB  - During the production of a traditional drink produced from the tubers of Cyperus
      esculentus L. also known as "horchata de chufa," a high quantity of by-products
      are generated. These by-products are rich with valuable biological compounds,
      hence, there is a need to report their extraction conditions for further use in
      food production as raw materials. Therefore, the objective of this study was to
      evaluate and improve the conventional extraction process, applied for recovery of
      phenolic compounds, total flavonoids, and total antioxidant capacity from the by
      products. Independent variables for extraction were: (i) Solvent type (mixtures
      of ethanol-water (v/v) at 0%, 25% and 50%); (ii) temperature (40, 50 and 60 
      degrees C), and (iii) extraction time (1, 2 and 3 h). The obtained results showed
      that solvent type, temperature, and time significantly influenced (p < 0.05) all
      investigated parameters. The highest content of total polyphenols (16.02 mg
      GAE/100 g of dry matter; d.m.), and total flavonoids (30.09 mg CE/100 g d.m.) was
      achieved by ethanol at 25% (v/v), after 3 h of extraction with temperatures of 60
      degrees C and 50  degrees C, respectively. The highest value of antioxidant
      capacity (1759.81 uM Trolox equivalents/g d.m.) was observed with 50% aqueous
      ethanol (v/v), at 60  degrees C, and 3 h of extraction. From the obtained
      results, it can be concluded that the by-products of "Horchata de Chufa" are an
      important source of antioxidant bioactive compounds.

PMID- 30275432
TI  - Polymerase Chain Reaction (PCR) as a Potential Point of Care Laboratory Test for
      Leprosy Diagnosis-A Systematic Review.
AB  - Leprosy is an infectious disease caused by Mycobacterium leprae and mainly
      affects skin, peripheral nerves, and eyes. Suitable tools for providing
      bacteriological evidence of leprosy are needed for early case detection and
      appropriate therapeutic management. Ideally these tools are applicable at all
      health care levels for the effective control of leprosy. This paper presents a
      systematic review analysis in order to investigate the performance of polymerase
      chain reaction (PCR) vis-a-vis slit skin smears (SSS) in various clinical
      settings and its potential usefulness as a routine lab test for leprosy
      diagnosis. Records of published journal articles were identified through PubMed
      database search. Twenty-seven articles were included for the analysis. The
      evidence from this review analysis suggests that PCR on skin biopsy is the ideal
      diagnostic test. Nevertheless, PCR on SSS samples also seems to be useful with
      its practical value for application, even at primary care levels. The review
      findings also indicated the necessity for improving the sensitivity of PCR and
      further research on specificity in ruling out other clinical conditions that may
      mimic leprosy. The M. leprae-specific repetitive element (RLEP) was the most
      frequently-used marker although its variable performance across the clinical
      sites and samples are a matter of concern. Undertaking further research studies
      with large sample numbers and uniform protocols studied simultaneously across
      multiple clinical sites is recommended to address these issues.

PMID- 30275431
TI  - Microplastics in Sediment and Surface Water of West Dongting Lake and South
      Dongting Lake: Abundance, Source and Composition.
AB  - Microplastic pollution was investigated in sediment and surface water in West
      Dongting Lake and South Dongting Lake for the first time. The abundance of
      microplastics ranged from 616.67 to 2216.67 items/m3 and 716.67 to 2316.67
      items/m3 in the lakeshore surface water of West Dongting Lake and South Dongting
      Lake, respectively. The highest levels of microplastic pollution were found in
      the lakes' outlets. In the lake center sites of the West Dongting Lake and South
      Dongting Lake, the abundance of microplastics ranged from 433.33 to 1500 items/m3
      and 366.67 to 1566.67 items/m3, respectively. Meanwhile, the study found that in
      lakeshore sediment of West Dongting Lake and South Dongting Lake, microplastic
      concentrations ranged from 320 to 480 items/m3 and 200-1150 items/m3. Polystyrene
      (PS) and polyethylene terephthalate (PET) were most common in the surface water
      and sediment samples, respectively. In addition, we suggest that the effects of
      polymer types in microplastics should be taken into account when considering
      abundance. This study can provide valuable points of reference to better
      understanding microplastic pollution in inland freshwater areas.

PMID- 30275433
TI  - Reputation-Aware Recruitment and Credible Reporting for Platform Utility in
      Mobile Crowd Sensing with Smart Devices in IoT.
AB  - The Internet of things (IoT) comprises a huge collection of electronic devices
      connected to the Internet to ensure the dependable exchange of sensing
      information. It involves mobile workers (MWs) who perform various activities to
      support enormous online services and applications. In mobile crowd sensing (MCS),
      a massive amount of sensing data is also generated by smart devices. Broadly, in
      the IoT, verifying the credibility and truthfulness of MWs' sensing reports is
      needed for MWs to expect attractive rewards. MWs are recruited by paying monetary
      incentives that must be awarded according to the quality and quantity of the
      task. The main problem is that MWs may perform false reporting by sharing low
      quality reported data to reduce the effort required. In the literature, false
      reporting is improved by hiring enough MWs for a task to evaluate the
      trustworthiness and acceptability of information by aggregating the submitted
      reports. However, it may not be possible due to budget constraints, or when
      malicious reporters are not identified and penalized properly. Recruitment is
      still not a refined process, which contributes to low sensing quality. This paper
      presents Reputation, Quality-aware Recruitment Platform (RQRP) to recruit MWs
      based on reputation for quality reporting with the intention of platform profit
      maximization in the IoT scenario. RQRP comprises two main phases: filtration in
      the selection of MWs and verifying the credibility of reported tasks. The former
      is focused on the selection of suitable MWs based on different criteria (e.g.,
      reputation, bid, expected quality, and expected platform utility), while the
      latter is more concerned with the verification of sensing quality, evaluation of
      reputation score, and incentives. We developed a testbed to evaluate and analyze
      the datasets, and a simulation was performed for data collection scenario from
      smart sensing devices. Results proved the superiority of RQRP against its
      counterparts in terms of truthfulness, quality, and platform profit maximization.
      To the best of our knowledge, we are the first to study the impact of truthful
      reporting on platform utility.

PMID- 30275435
TI  - Allogeneic CAR-T Cells: More than Ease of Access?
AB  - Patient derived anti-CD19 chimeric antigen receptor-T (CAR-T) cells are a
      powerful tool in achieving a complete remission in a range of B-cell
      malignancies, most notably B-acute lymphoblastic leukaemia (B-ALL) and diffuse
      large B-cell lymphoma (DLBCL). However, there are limitations, including
      inability to manufacture CAR-T cells from the patient's own T cells, disease
      progression and death prior to return of engineered cells. T cell dysfunction is
      known to occur in cancer patients, and several groups have recently described
      differences in CAR-T cells generated from chronic lymphocytic leukaemia (CLL)
      patients compared with those from a healthy donor. This is thought to contribute
      to the low response rate in this disease group. Healthy donor, gene-edited CAR-T
      cells which do not require human leucocyte antigen (HLA) matching have the
      potential to provide an 'off the shelf' product, overcoming the manufacturing
      difficulties of producing CAR-T cells for each individual patient. They may also
      provide a more functional, potent product for malignancies such as CLL, where T
      cell dysfunction is common and frequently cannot be fully reversed during the
      manufacturing process. Here we review the potential benefits and obstacles for
      healthy donor, allogeneic CAR-T cells.

PMID- 30275436
TI  - Validation of an Improved Statistical Theory for Sea Surface Whitecap Coverage
      Using Satellite Remote Sensing Data.
AB  - The whitecap coverage at the sea surface is affected by the ratio of kinetic
      energy to potential energy, theta, the wave spectrum width parameter, rho, and
      other factors. This paper validates an improved statistical theory for surface
      whitecap coverage. Based on the theoretical analysis, we find that the whitecap
      coverage is more sensitive to rho than to theta, and the improved statistical
      theory for surface whitecap coverage is suitable in regions of rough winds and
      waves. The satellite-derived whitecap coverage data in the westerly wind zone is
      used to validate the improved theory. The comparison between the results from
      theory and observations displays a better performance from the improved theory
      relative to the other methods tested.

PMID- 30275434
TI  - Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or
      New Therapeutic Target.
AB  - Trimethylamine N-oxide (TMAO) is a molecule generated from choline, betaine, and
      carnitine via gut microbial metabolism. The plasma level of TMAO is determined by
      several factors including diet, gut microbial flora, drug administration and
      liver flavin monooxygenase activity. In humans, recent clinical studies evidence
      a positive correlation between elevated plasma levels of TMAO and an increased
      risk for major adverse cardiovascular events. A direct correlation between
      increased TMAO levels and neurological disorders has been also hypothesized.
      Several therapeutic strategies are being explored to reduce TMAO levels,
      including use of oral broad spectrum antibiotics, promoting the growth of
      bacteria that use TMAO as substrate and the development of target-specific
      molecules. Despite the accumulating evidence, it is questioned whether TMAO is
      the mediator of a bystander in the disease process. Thus, it is important to
      undertake studies to establish the role of TMAO in human health and disease. In
      this article, we reviewed dietary sources and metabolic pathways of TMAO, as well
      as screened the studies suggesting possible involvement of TMAO in the etiology
      of cardiovascular and neurological disorders, underlying the importance of TMAO
      mediating inflammatory processes. Finally, the potential utility of TMAO as
      therapeutic target is also analyzed.

PMID- 30275437
TI  - A Swarming Approach to Optimize the One-Hop Delay in Smart Driving Inter-Platoon
      Communications.
AB  - Multi-platooning is an important management strategy for autonomous driving
      technology. The backbone vehicles in a multi-platoon adopt the IEEE 802.11
      distributed coordination function (DCF) mechanism to transmit vehicles'
      kinematics information through inter-platoon communications, and then forward the
      information to the member vehicles through intra-platoon communications. In this
      case, each vehicle in a multi-platoon can acquire the kinematics information of
      other vehicles. The parameters of DCF, the hidden terminal problem and the number
      of neighbors may incur a long and unbalanced one-hop delay of inter-platoon
      communications, which would further prolong end-to-end delay of inter-platoon
      communications. In this case, some vehicles within a multi-platoon cannot acquire
      the emergency changes of other vehicles' kinematics within a limited time
      duration and take prompt action accordingly to keep a multi-platoon formation.
      Unlike other related works, this paper proposes a swarming approach to optimize
      the one-hop delay of inter-platoon communications in a multi-platoon scenario.
      Specifically, the minimum contention window size of each backbone vehicle is
      adjusted to enable the one-hop delay of each backbone vehicle to get close to the
      minimum average one-hop delay. The simulation results indicate that, the one-hop
      delay of the proposed approach is reduced by 12% as compared to the DCF mechanism
      with the IEEE standard contention window size. Moreover, the end-to-end delay,
      one-hop throughput, end-to-end throughput and transmission probability have been
      significantly improved.

PMID- 30275438
TI  - Fence Angioplasty Prevents Narrowing of Venous Anastomosis in Solitary Pancreas
      Transplant.
AB  - BACKGROUND Graft thrombosis is the leading cause of early graft failure in
      pancreas transplants. Direct anastomosis grafting of the portal vein to the iliac
      vein or vena cava generally appears narrowed on postoperative computed tomography
      (CT) scans. However, modification of surgical techniques may prevent venous
      narrowing, which also prevents thrombosis-related graft failure. MATERIAL AND
      METHODS We performed 31 solitary pancreas transplants since 2015. Retrospective
      analysis of these patients was performed. RESULTS Fence angioplasty was applied
      in the final 12 cases, and no technical failures or early graft losses occurred
      in these cases. Three graft losses, including 2 immunologic losses and 1 patient
      death with functioning graft, occurred after at least postoperative 4 months. The
      venous anastomoses were evaluated via intraoperative Doppler ultrasound and
      postoperative CT scans. Intraoperative Doppler ultrasound revealed improved
      spectral waves of venous anastomoses in the fence group (monophasic spectral
      wave, 42.9% vs. 0%, p=0.017). The fence-graft applied group had no cases of
      narrowing, whereas the non-fence group had high narrowing rates on CT scans
      (84.2% vs. 0%, p<0.001). Furthermore, with less use of postoperative heparin,
      postoperative bleeding rates were lower in the fence group (36% vs. 0%, p=0.026).
      CONCLUSIONS Fence angioplasty is a definitive method for avoiding venous
      anastomotic stenosis and preventing graft failure due to thrombosis.

PMID- 30275439
TI  - Three-Dimensional Volume Imaging to Increase the Accuracy of Surgical Management
      in a Case of Recurrent Chordoma of the Clivus.
AB  - BACKGROUND The clivus is a depression in the anterior occipital bone of the skull
      base, posterior to the dorsum sellae, at the junction with the sphenoid bone.
      Chordoma is a rare tumor arising from embryonic remnants of the notochord and can
      be locally aggressive with a tendency to recur. The optimal management of this
      rare tumor remains controversial. A report of a case of recurrent chordoma of the
      clivus is presented to illustrate the value of volumetric three-dimensional (3-D)
      reconstruction with computed tomography (CT) and magnetic resonance imaging (MRI)
      to determine optimal surgical management. CASE REPORT A 53-year-old man presented
      with pain in the right orbital cavity, right proptosis, swelling of the right
      cheek, and bilateral loss of vision. He also had adrenal insufficiency. CT and
      contrast-enhanced (gadolinium) T1-weighted MRI with multiplanar acquisition were
      performed with volumetric 3-D reconstruction of the tumor, to increase the
      chances of treatment success. Surgical resection was performed to remove the
      tumor and reduce the risk of recurrence. Histology of the tumor was consistent
      with chordoma, supported by positive immunohistochemical staining for S-100 and
      epithelial membrane antigen (EMA). CONCLUSIONS This report highlighted the value
      of 3-D volume imaging in the diagnosis and treatment planning in a rare case of
      recurrent chordoma of the clivus. Analysis of tumor volume may be an indicator of
      the efficacy of surgery, complementing the Response Evaluation Criteria In Solid
      Tumors (RECIST) system and as a valuable tool to predict treatment outcome.

PMID- 30275440
TI  - DNA Repair Gene (XPD, XRCC4, and XRCC1) Polymorphisms in Patients with
      Endometrial Hyperplasia: A Pilot Study.
AB  - BACKGROUND In this study, we aimed to evaluate the association between
      endometrial hyperplasia and DNA repair gene (XPD, XRCC4, and XRCC1)
      polymorphisms. MATERIAL AND METHODS There were 114 cases enrolled in the study in
      4 groups: simple endometrial hyperplasia (SH) (Group 1), complex endometrial
      hyperplasia without atypia (CH) (Group 2), complex atypical endometrial
      hyperplasia (CAH) (Group 3), and normal endometrium (NE) (Group 4). Of these
      cases, 37 cases had SH, 36 cases had CH, 16 cases had CAH, and 25 cases had NE.
      To evaluate an association between atypia and DNA repair genes, we consider a
      group that included both SH and CH, the endometrial hyperplasia without atypia
      cases (Group 5). Genomic DNA was isolated from paraffin-embedded endometrial
      tissue collected from the Pathology Department of Gaziantep University Medical
      School. Polymerase chain reaction (PCR) and/or restriction fragment length
      polymorphism (RFLP) method was used for evaluating of XPD (-751), XRCC4 (-1394
      and a variable number of tandem repeats in intron 3), and XRCC1 (-399) genes.
      RESULTS We observed a notable distinction in patients having endometrial
      hyperplasia without atypia (the SH+CH group) and the CAH group in terms of XPD (
      751) gene polymorphisms. A notable contrast was observed in patients with
      endometrial hyperplasia without atypia (the SH+CH group) and the NE group in
      terms of XRCC4 (VNTR intron 3) polymorphisms (P=0.026, P=0.018, respectively).
      CONCLUSIONS It was evident the DNA repair gene XPD and XRCC4 polymorphisms had a
      role in the pathophysiology of endometrial hyperplasia.

PMID- 30275441
TI  - Metformin Increases Cardiac Rupture After Myocardial Infarction via the AMPK
      MTOR/PGC-1alpha Signaling Pathway in Rats with Acute Myocardial Infarction.
AB  - BACKGROUND Cardiac rupture often occurs after acute myocardial infarction due to
      complex and unclear pathogenesis. This study investigated whether metformin
      increases the incidence of cardiac rupture after myocardial infarction through
      the AMPK-MTOR/PGC-1alpha signaling pathway. MATERIAL AND METHODS An acute
      myocardial infarction (MI) mouse model was established. A series of experiments
      involving RT-qPCR, Western blot, TUNEL staining, and Masson staining were
      performed in this study. RESULTS Myocardial infarction occurred, resulting in the
      cardiac rupture, and the expression level of PGC-1alpha increased in the cardiac
      myocardium. Meanwhile, the proportion of myocardial NT-PGC-1alpha/PGC-1alpha
      decreased. The expression level of myocardial PGC-1alpha in MI mice with cardiac
      rupture after MI was significantly higher than that in the mice without cardiac
      rupture, and the ratio of myocardial NT-PGC-1alpha/PGC-1alpha was low. In
      addition, increasing the dose of metformin significantly increased the incidence
      of cardiac rupture after myocardial infarction in MI mice. High-dose metformin
      caused cardiac rupture in MI mice. Moreover, high-dose metformin (Met 2.0 nM)
      reduces the proportion of NT-PGC-1alpha/PGC-1alpha in primary cardiomyocytes of
      SD mice (SD-NRVCs [Neonatal rat ventricular cardiomyocytes]), and its effect was
      inhibited by Compound C (AMPK inhibitor). Further, after 3 days of treatment with
      high-dose metformin in MI mice, myocardial fibrin synthesis decreased and
      fibrosis was significantly inhibited. Meanwhile, cardiomyocyte apoptosis
      increased significantly. With the increase in metformin concentration, the
      expression level of myocardial LC3b gradually increased in MI mice, suggesting
      that metformin enhances the autophagy of cardiomyocytes. CONCLUSIONS These
      results suggest that metformin increases cardiac rupture after myocardial
      infarction through the AMPK-MTOR/PGC-1alpha signaling pathway.

PMID- 30275442
TI  - Femtosecond photoexcitation dynamics inside a quantum solvent.
AB  - The observation of chemical reactions on the time scale of the motion of
      electrons and nuclei has been made possible by lasers with ever shortened pulse
      lengths. Superfluid helium represents a special solvent that permits the
      synthesis of novel classes of molecules that have eluded dynamical studies so
      far. However, photoexcitation inside this quantum solvent triggers a pronounced
      response of the solvation shell, which is not well understood. Here, we present a
      mechanistic description of the solvent response to photoexcitation of indium (In)
      dopant atoms inside helium nanodroplets (HeN), obtained from femtosecond pump
      probe spectroscopy and time-dependent density functional theory simulations. For
      the In-HeN system, part of the excited state electronic energy leads to expansion
      of the solvation shell within 600 fs, initiating a collective shell oscillation
      with a period of about 30 ps. These coupled electronic and nuclear dynamics will
      be superimposed on intrinsic photoinduced processes of molecular systems inside
      helium droplets.

PMID- 30275443
TI  - Carrier density and disorder tuned superconductor-metal transition in a two
      dimensional electron system.
AB  - Quantum ground states that arise at atomically controlled oxide interfaces
      provide an opportunity to address key questions in condensed matter physics,
      including the nature of two-dimensional metallic behaviour often observed
      adjacent to superconductivity. At the superconducting LaAlO3/SrTiO3 interface, a
      metallic ground state emerges upon the collapse of superconductivity with field
      effect gating and is accompanied with a pseudogap. Here we utilize independent
      control of carrier density and disorder of the interfacial superconductor using
      dual electrostatic gates, which enables the comprehensive examination of the
      electronic phase diagram approaching zero temperature. We find that the pseudogap
      corresponds to precursor pairing, and the onset of long-range phase coherence
      forms a two-dimensional superconducting dome as a function of the dual-gate
      voltages. The gate-tuned superconductor-metal transitions are driven by
      macroscopic phase fluctuations of Josephson coupled superconducting puddles.

PMID- 30275444
TI  - Silencing of TGFbeta signalling in microglia results in impaired homeostasis.
AB  - TGFbeta1 has been implicated in regulating functional aspects of several distinct
      immune cell populations including central nervous system (CNS) resident
      microglia. Activation and priming of microglia have been demonstrated to
      contribute to the progression of neurodegenerative diseases and, thus, underlie
      stringent control by endogenous regulatory factors including TGFbeta1. Here, we
      demonstrate that deletion of Tgfbr2 in adult postnatal microglia does neither
      result in impairment of the microglia-specific gene expression signatures, nor is
      microglial survival and maintenance affected. Tgfbr2-deficient microglia were
      characterised by distinct morphological changes and transcriptome analysis using
      RNAseq revealed that loss of TGFbeta signalling results in upregulation of
      microglia activation and priming markers. Moreover, protein arrays demonstrated
      increased secretion of CXCL10 and CCL2 accompanied by activation of immune cell
      signalling as evidenced by increased phosphorylation of TAK1. Together, these
      data underline the importance of microglial TGFbeta signalling to regulate
      microglia adaptive changes.

PMID- 30275446
TI  - Strong coupling and induced transparency at room temperature with single quantum
      dots and gap plasmons.
AB  - Coherent coupling between plasmons and transition dipole moments in emitters can
      lead to two distinct spectral effects: vacuum Rabi splitting at strong coupling
      strengths, and induced transparency (also known as Fano interference) at
      intermediate coupling strengths. Achieving either strong or intermediate coupling
      between a single emitter and a localized plasmon resonance has the potential to
      enable single-photon nonlinearities and other extreme light-matter interactions,
      at room temperature and on the nanometer scale. Both effects produce two peaks in
      the spectrum of scattering from the plasmon resonance, and can thus be confused
      if scattering measurements alone are performed. Here we report measurements of
      scattering and photoluminescence from individual coupled plasmon-emitter systems
      that consist of a single colloidal quantum dot in the gap between a gold
      nanoparticle and a silver film. The measurements unambiguously demonstrate weak
      coupling (the Purcell effect), intermediate coupling (Fano interference), and
      strong coupling (Rabi splitting) at room temperature.

PMID- 30275445
TI  - Analysis of chromatin accessibility uncovers TEAD1 as a regulator of migration in
      human glioblastoma.
AB  - The intrinsic drivers of migration in glioblastoma (GBM) are poorly understood.
      To better capture the native molecular imprint of GBM and its developmental
      context, here we isolate human stem cell populations from GBM (GSC) and germinal
      matrix tissues and map their chromatin accessibility via ATAC-seq. We uncover two
      distinct regulatory GSC signatures, a developmentally shared/proliferative and a
      tumor-specific/migratory one in which TEAD1/4 motifs are uniquely
      overrepresented. Using ChIP-PCR, we validate TEAD1 trans occupancy at
      accessibility sites within AQP4, EGFR, and CDH4. To further characterize TEAD's
      functional role in GBM, we knockout TEAD1 or TEAD4 in patient-derived GBM lines
      using CRISPR-Cas9. TEAD1 ablation robustly diminishes migration, both in vitro
      and in vivo, and alters migratory and EMT transcriptome signatures with
      consistent downregulation of its target AQP4. TEAD1 overexpression restores AQP4
      expression, and both TEAD1 and AQP4 overexpression rescue migratory deficits in
      TEAD1-knockout cells, implicating a direct regulatory role for TEAD1-AQP4 in GBM
      migration.

PMID- 30275447
TI  - Efficient photocatalytic hydrogen evolution with ligand engineered all-inorganic
      InP and InP/ZnS colloidal quantum dots.
AB  - Photocatalytic hydrogen evolution is a promising technique for the direct
      conversion of solar energy into chemical fuels. Colloidal quantum dots with
      tunable band gap and versatile surface properties remain among the most prominent
      targets in photocatalysis despite their frequent toxicity, which is detrimental
      for environmentally friendly technological implementations. In the present work,
      all-inorganic sulfide-capped InP and InP/ZnS quantum dots are introduced as
      competitive and far less toxic alternatives for photocatalytic hydrogen evolution
      in aqueous solution, reaching turnover numbers up to 128,000 based on quantum
      dots with a maximum internal quantum yield of 31%. In addition to the favorable
      band gap of InP quantum dots, in-depth studies show that the high efficiency also
      arises from successful ligand engineering with sulfide ions. Due to their small
      size and outstanding hole capture properties, sulfide ions effectively extract
      holes from quantum dots for exciton separation and decrease the physical and
      electrical barriers for charge transfer.

PMID- 30275449
TI  - Engineering functional BMP-2 expressing teratoma-derived fibroblasts for
      enhancing osteogenesis.
AB  - Bone morphogenetic protein 2 (BMP-2) is considered an effective growth factor for
      bone formation, and is used for making osteo-inductive scaffolds, but the related
      clinical investigations have shown low success rates. In this study, we
      genetically manipulated teratoma-derived fibroblast (TDF) cells by simultaneous
      introduction of BMP-2 and herpes simplex virus-thymidine kinase (HSV-tk) encoding
      genes. Self-production of BMP-2 in TDF cells strongly enhanced the alkaline
      phosphatase (ALP) activity, calcium content, and elevated the mRNA expression of
      osteogenic marker genes during in vitro osteogenesis. The bone formation volume
      was also remarkably enhanced in calvarial and femoral critical-size defect
      models. Ganciclovir (GCV) treatment induced apoptosis in TDF cells co-expressing
      HSV-tk and BMP-2, implying that HSV-tk suicide gene can modulate the side-effects
      of stem cell therapy, e.g., development of uncontrollable teratoma and tumor
      formation. Altogether, our findings revealed a safe and highly efficient
      technique with potential therapeutic applications for bone regeneration.

PMID- 30275448
TI  - Outward open conformation of a Major Facilitator Superfamily multidrug/H+
      antiporter provides insights into switching mechanism.
AB  - Multidrug resistance (MDR) poses a major challenge to medicine. A principle cause
      of MDR is through active efflux by MDR transporters situated in the bacterial
      membrane. Here we present the crystal structure of the major facilitator
      superfamily (MFS) drug/H+ antiporter MdfA from Escherichia coli in an outward
      open conformation. Comparison with the inward facing (drug binding) state shows
      that, in addition to the expected change in relative orientations of the N- and C
      terminal lobes of the antiporter, the conformation of TM5 is kinked and twisted.
      In vitro reconstitution experiments demonstrate the importance of selected
      residues for transport and molecular dynamics simulations are used to gain
      insights into antiporter switching. With the availability of structures of
      alternative conformational states, we anticipate that MdfA will serve as a model
      system for understanding drug efflux in MFS MDR antiporters.

PMID- 30275450
TI  - Author Correction: Tropical protected areas reduced deforestation carbon
      emissions by one third from 2000-2012.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30275451
TI  - Nitrogen Dynamics in Soil Fertilized with Slow Release Brown Coal-Urea
      Fertilizers.
AB  - Reducing the release rate of urea can increase its use efficiency and minimize
      negative effects on the environment. A novel fertilizer material that was formed
      by blending brown coal (BC) with urea, delayed fertilizer N release in controlled
      climatic conditions in a glasshouse, through strong retention facilitated by the
      extensive surface area, porous structure and chemical functional groups in the
      BC. However, the role of BC as a carrier of synthetic urea and the effect of
      their interaction with various soil types on the dynamics and mineralization of N
      remains largely unclear. Therefore, a soil column incubation study was conducted
      to assess the release, transformation and transportation of N from several
      different brown coal-urea (BCU) granules, compared to commercial urea. Blending
      and subsequent granulation of urea with BC substantially increased fertilizer N
      retention in soil by decreasing gaseous emissions and leaching of N compared to
      urea alone, irrespective of soil type. The BCU granule containing the highest
      proportion of BC had lower leaching and gaseous emissions and maintained
      considerably higher mineral and mineralizable N in topsoil. Possible modes of
      action of the BCU granules have been proposed, emphasizing the role of BC in
      enhancing N retention over a longer period of time. The results support the
      notion that BCU granules can be used as a slow release and enhanced efficiency
      fertilizer for increasing availability and use efficiency of N by crops.

PMID- 30275452
TI  - Transcriptome Analysis of Intrusively Growing Flax Fibers Isolated by Laser
      Microdissection.
AB  - The intrusive growth, a type of plant cell elongation occurring in the depths of
      plant tissues, is characterized by the invasion of a growing cell between its
      neighbours due to a higher rate of elongation. In order to reveal the largely
      unknown molecular mechanisms of intrusive growth, we isolated primary flax phloem
      fibers specifically at the stage of intrusive growth by laser microdissection.
      The comparison of the RNA-Seq data from several flax stem parts enabled the
      characterization of those processes occurring specifically during the fiber
      intrusive elongation. The revealed molecular players are summarized as those
      involved in the supply of assimilates and support of turgor pressure, cell wall
      enlargement and modification, regulation by transcription factors and hormones,
      and responses to abiotic stress factors. The data obtained in this study provide
      a solid basis for developing approaches to manipulate fiber intrusive elongation,
      which is of importance both for plant biology and the yield of fiber crops.

PMID- 30275453
TI  - Partial depletion of CD206-positive M2-like macrophages induces proliferation of
      beige progenitors and enhances browning after cold stimulation.
AB  - Beige adipocytes are an inducible form of thermogenic adipocytes that become
      interspersed within white adipose tissue (WAT) depots in response to cold
      exposure. Previous studies have shown that type 2 cytokines and M2 macrophages
      induce cold-induced browning in inguinal WAT (ingWAT) by producing
      catecholamines. Exactly how the conditional and partial depletion of CD206+ M2
      like macrophages regulates the cold-induced browning of ingWAT, however, remains
      unknown. We examined the role of CD206+ M2-like macrophages in the cold-induced
      browning of WAT using genetically engineered CD206DTR mice, in which CD206+ M2
      like macrophages were conditionally depleted. The partial depletion of CD206+ M2
      like enhanced UCP1 expression in ingWAT, as shown by immunostaining, and also
      upregulated the expression of Ucp1 and other browning-related marker genes in
      ingWAT after cold exposure. A flow cytometry analysis showed that the partial
      depletion of CD206+ M2-like macrophages caused an increase in the number of beige
      progenitors in ingWAT in response to cold. Thus, we concluded that CD206+ M2-like
      macrophages inhibit the proliferation of beige progenitors and that the partial
      depletion of CD206+ M2-like macrophages releases this inhibition, thereby
      enhancing browning and insulin sensitivity.

PMID- 30275454
TI  - Damage-induced reactive oxygen species enable zebrafish tail regeneration by
      repositioning of Hedgehog expressing cells.
AB  - Many aquatic vertebrates have a remarkable ability to regenerate limbs and tails
      after amputation. Previous studies indicate that reactive oxygen species (ROS)
      signalling initiates regeneration, but the mechanism by which this takes place is
      poorly understood. Developmental signalling pathways have been shown to have
      proregenerative roles in many systems. However, whether these are playing roles
      that are specific to regeneration, or are simply recapitulating their
      developmental functions is unclear. Here, we analyse zebrafish larval tail
      regeneration and find evidence that ROS released upon wounding cause
      repositioning of notochord cells to the damage site. These cells secrete Hedgehog
      ligands that are required for regeneration. Hedgehog signalling is not required
      for normal tail development suggesting that it has a regeneration-specific role.
      Our results provide a model for how ROS initiate tail regeneration, and indicate
      that developmental signalling pathways can play regenerative functions that are
      not directly related to their developmental roles.

PMID- 30275455
TI  - Small-molecule AgrA inhibitors F12 and F19 act as antivirulence agents against
      Gram-positive pathogens.
AB  - Small-molecule antivirulence agents represent a promising alternative or adjuvant
      to antibiotics. These compounds disarm pathogens of disease-causing toxins
      without killing them, thereby diminishing survival pressure to develop
      resistance. Here we show that the small-molecule antivirulence agents F12 and F19
      block staphylococcal transcription factor AgrA from binding to its promoter.
      Consequently, toxin expression is inhibited, thus preventing host cell damage by
      Gram-positive pathogens. Broad spectrum efficacy against Gram-positive pathogens
      is due to the existence of AgrA homologs in many Gram-positive bacteria. F12 is
      more efficacious in vitro and F19 works better in vivo. In a murine MRSA
      bacteremia/sepsis model, F19 treatment alone resulted in 100% survival while
      untreated animals had 70% mortality. Furthermore, F19 enhances antibiotic
      efficacy in vivo. Notably, in a murine MRSA wound infection model, combination of
      F19 with antibiotics resulted in bacterial load reduction. Thus, F19 could be
      used alone or in combination with antibiotics to prevent and treat infections of
      Gram-positive pathogens.

PMID- 30275456
TI  - Author Correction: A Multiwell-Based Detection Platform with Integrated PDMS
      Concentrators for Rapid Multiplexed Enzymatic Assays.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30275457
TI  - Multibandgap quantum dot ensembles for solar-matched infrared energy harvesting.
AB  - As crystalline silicon solar cells approach in efficiency their theoretical
      limit, strategies are being developed to achieve efficient infrared energy
      harvesting to augment silicon using solar photons from beyond its 1100 nm
      absorption edge. Herein we report a strategy that uses multi-bandgap lead sulfide
      colloidal quantum dot (CQD) ensembles to maximize short-circuit current and open
      circuit voltage simultaneously. We engineer the density of states to achieve
      simultaneously a large quasi-Fermi level splitting and a tailored optical
      response that matches the infrared solar spectrum. We shape the density of states
      by selectively introducing larger-bandgap CQDs within a smaller-bandgap CQD
      population, achieving a 40 meV increase in open-circuit voltage. The near-unity
      internal quantum efficiency in the optimized multi-bandgap CQD ensemble yielded a
      maximized photocurrent of 3.7 +/- 0.2 mA cm-2. This provides a record for silicon
      filtered power conversion efficiency equal to one power point, a 25% (relative)
      improvement compared to the best previously-reported results.

PMID- 30275461
TI  - Childhood weight gain and oral microbiota.

PMID- 30275458
TI  - Menstrual cycle rhythmicity: metabolic patterns in healthy women.
AB  - The menstrual cycle is an essential life rhythm governed by interacting levels of
      progesterone, estradiol, follicular stimulating, and luteinizing hormones. To
      study metabolic changes, biofluids were collected at four timepoints in the
      menstrual cycle from 34 healthy, premenopausal women. Serum hormones, urinary
      luteinizing hormone and self-reported menstrual cycle timing were used for a 5
      phase cycle classification. Plasma and urine were analyzed using LC-MS and GC-MS
      for metabolomics and lipidomics; serum for clinical chemistries; and plasma for B
      vitamins using HPLC-FLD. Of 397 metabolites and micronutrients tested, 208 were
      significantly (p < 0.05) changed and 71 reached the FDR 0.20 threshold showing
      rhythmicity in neurotransmitter precursors, glutathione metabolism, the urea
      cycle, 4-pyridoxic acid, and 25-OH vitamin D. In total, 39 amino acids and
      derivatives and 18 lipid species decreased (FDR < 0.20) in the luteal phase,
      possibly indicative of an anabolic state during the progesterone peak and
      recovery during menstruation and the follicular phase. The reduced metabolite
      levels observed may represent a time of vulnerability to hormone related health
      issues such as PMS and PMDD, in the setting of a healthy, rhythmic state. These
      results provide a foundation for further research on cyclic differences in
      nutrient-related metabolites and may form the basis of novel nutrition strategies
      for women.

PMID- 30275462
TI  - Metabolic adaptations to high-fat diet.

PMID- 30275460
TI  - The role of hypoxia-inducible factors in metabolic diseases.
AB  - Hypoxia-inducible factors (HIFs), a family of transcription factors activated by
      hypoxia, consist of three alpha-subunits (HIF1alpha, HIF2alpha and HIF3alpha) and
      one beta-subunit (HIF1beta), which serves as a heterodimerization partner of the
      HIFalpha subunits. HIFalpha subunits are stabilized from constitutive degradation
      by hypoxia largely through lowering the activity of the oxygen-dependent prolyl
      hydroxylases that hydroxylate HIFalpha, leading to their proteolysis. HIF1alpha
      and HIF2alpha are expressed in different tissues and regulate target genes
      involved in angiogenesis, cell proliferation and inflammation, and their
      expression is associated with different disease states. HIFs have been widely
      studied because of their involvement in cancer, and HIF2alpha-specific inhibitors
      are being investigated in clinical trials for the treatment of kidney cancer.
      Although cancer has been the major focus of research on HIF, evidence has emerged
      that this pathway has a major role in the control of metabolism and influences
      metabolic diseases such as obesity, type 2 diabetes mellitus and non-alcoholic
      fatty liver disease. Notably increased HIF1alpha and HIF2alpha signalling in
      adipose tissue and small intestine, respectively, promotes metabolic diseases in
      diet-induced disease models. Inhibition of HIF1alpha and HIF2alpha decreases the
      adverse diet-induced metabolic phenotypes, suggesting that they could be drug
      targets for the treatment of metabolic diseases.

PMID- 30275459
TI  - FIBP knockdown attenuates growth and enhances chemotherapy in colorectal cancer
      via regulating GSK3beta-related pathways.
AB  - Colorectal cancer stem cells (CSCs), characterized by self-renewal ability and
      high expression of proliferative genes, contribute to the chemoresistance of
      colorectal cancer (CRC). We aimed to identify the molecular mechanisms underlying
      CRC chemoresistance through comprehensive bioinformatics screenings and
      experimental confirmation of gene functions. We found that high expression of
      FGF1 intracellular binding protein (FIBP) was correlated with chemoresistance and
      poor prognosis in CRC patients. Therefore, the chemoresistant CRC cell line
      HCT116-CSC with high expression of the stem cell markers CD44 and CD133 was
      established for further phenotypic tests. FIBP knockdown inhibited proliferation,
      enhanced chemotherapy effects, and attenuated the stemness markers of CRC cells
      in vivo and in vitro. Through RNA-seq and gene set enrichment analysis, we
      identified cyclin D1 as a key downstream target in FIBP-regulated cell cycle
      progression and proliferation. Moreover, FIBP bound to GSK3beta, inhibited its
      phosphorylation at Tyr216, and activated beta-catenin/TCF/cyclin D1 signaling in
      HCT116-CSCs. Additional GSK3beta knockdown reversed the FIBP silencing-induced
      inhibition of proliferation and decreased stemness marker expression in HCT116
      CSCs. Furthermore, DNA methylation profiling suggested that FIBP regulated the
      stemness of CRC cells via methylation activity that was dependent on GSK3beta but
      independent of beta-catenin signaling. Our data illuminate the potential of FIBP
      as a novel therapeutic target for treating chemoresistant CRC through inhibition
      of GSK3beta-related signaling.

PMID- 30275463
TI  - Islet encapsulation therapy - racing towards the finish line?

PMID- 30275464
TI  - It's about time.

PMID- 30275465
TI  - Rapid sex-specific evolution of age at maturity is shaped by genetic architecture
      in Atlantic salmon.
AB  - Understanding the mechanisms by which populations adapt to their environments is
      a fundamental aim in biology. However, it remains challenging to identify the
      genetic basis of traits, provide evidence of genetic changes and quantify
      phenotypic responses. Age at maturity in Atlantic salmon represents an ideal
      trait to study contemporary adaptive evolution as it has been associated with a
      single locus in the vgll3 region and has also strongly changed in recent decades.
      Here, we provide an empirical example of contemporary adaptive evolution of a
      large-effect locus driving contrasting sex-specific evolutionary responses at the
      phenotypic level. We identified an 18% decrease in the vgll3 allele associated
      with late maturity in a large and diverse salmon population over 36 years,
      induced by sex-specific selection during sea migration. Those genetic changes
      resulted in a significant evolutionary response only in males, due to sex
      specific dominance patterns and vgll3 allelic effects. The vgll3 allelic and
      dominance effects differed greatly in a second population and were likely to
      generate different selection and evolutionary patterns. Our study highlights the
      importance of knowledge of genetic architecture to better understand fitness
      trait evolution and phenotypic diversity. It also emphasizes the potential role
      of adaptive evolution in the trend towards earlier maturation observed in
      numerous Atlantic salmon populations worldwide.

PMID- 30275466
TI  - Personality shapes pair bonding in a wild bird social system.
AB  - Mated pair bonds are integral to many animal societies, yet how individual
      variation in behaviour influences their formation remains largely unknown. In a
      population of wild great tits (Parus major), we show that personality shapes pair
      bonding: proactive males formed stronger pre-breeding pair bonds by meeting their
      future partners sooner and increasing their relationship strength at a faster
      rate. As a result, proactive males sampled fewer potential mates. Thus,
      personality may have important implications for social relationship dynamics and
      emergent social structure.

PMID- 30275467
TI  - Mechanotransduction is required for establishing and maintaining mature inner
      hair cells and regulating efferent innervation.
AB  - In the adult auditory organ, mechanoelectrical transducer (MET) channels are
      essential for transducing acoustic stimuli into electrical signals. In the
      absence of incoming sound, a fraction of the MET channels on top of the sensory
      hair cells are open, resulting in a sustained depolarizing current. By
      genetically manipulating the in vivo expression of molecular components of the
      MET apparatus, we show that during pre-hearing stages the MET current is
      essential for establishing the electrophysiological properties of mature inner
      hair cells (IHCs). If the MET current is abolished in adult IHCs, they revert
      into cells showing electrical and morphological features characteristic of pre
      hearing IHCs, including the re-establishment of cholinergic efferent innervation.
      The MET current is thus critical for the maintenance of the functional properties
      of adult IHCs, implying a degree of plasticity in the mature auditory system in
      response to the absence of normal transduction of acoustic signals.

PMID- 30275469
TI  - Lysosomal storage diseases.
AB  - Lysosomal storage diseases (LSDs) are a group of over 70 diseases that are
      characterized by lysosomal dysfunction, most of which are inherited as autosomal
      recessive traits. These disorders are individually rare but collectively affect 1
      in 5,000 live births. LSDs typically present in infancy and childhood, although
      adult-onset forms also occur. Most LSDs have a progressive neurodegenerative
      clinical course, although symptoms in other organ systems are frequent. LSD
      associated genes encode different lysosomal proteins, including lysosomal enzymes
      and lysosomal membrane proteins. The lysosome is the key cellular hub for
      macromolecule catabolism, recycling and signalling, and defects that impair any
      of these functions cause the accumulation of undigested or partially digested
      macromolecules in lysosomes (that is, 'storage') or impair the transport of
      molecules, which can result in cellular damage. Consequently, the cellular
      pathogenesis of these diseases is complex and is currently incompletely
      understood. Several LSDs can be treated with approved, disease-specific therapies
      that are mostly based on enzyme replacement. However, small-molecule therapies,
      including substrate reduction and chaperone therapies, have also been developed
      and are approved for some LSDs, whereas gene therapy and genome editing are at
      advanced preclinical stages and, for a few disorders, have already progressed to
      the clinic.

PMID- 30275470
TI  - Interface dominated cooperative nanoprecipitation in interstitial alloys.
AB  - Steels belong to one of the best established materials, however, the mechanisms
      of various phase transformations down to the nano length scale are still not
      fully clear. In this work, high-resolution transmission electron microscopy is
      combined with atomistic simulations to study the nanoscale carbide precipitation
      in a Fe-Cr-C alloy. We identify a cooperative growth mechanism that connects host
      lattice reconstruction and interstitial segregation at the growing interface
      front, which leads to a preferential growth of cementite (Fe3C) nanoprecipitates
      along a particular direction. This insight significantly improves our
      understanding of the mechanisms of nanoscale precipitation in interstitial
      alloys, and paves the way for engineering nanostructures to enhance the
      mechanical performance of alloys.

PMID- 30275468
TI  - Cell-specific proteome analyses of human bone marrow reveal molecular features of
      age-dependent functional decline.
AB  - Diminishing potential to replace damaged tissues is a hallmark for ageing of
      somatic stem cells, but the mechanisms remain elusive. Here, we present proteome
      wide atlases of age-associated alterations in human haematopoietic stem and
      progenitor cells (HPCs) and five other cell populations that constitute the bone
      marrow niche. For each, the abundance of a large fraction of the ~12,000 proteins
      identified is assessed in 59 human subjects from different ages. As the HPCs
      become older, pathways in central carbon metabolism exhibit features reminiscent
      of the Warburg effect, where glycolytic intermediates are rerouted towards
      anabolism. Simultaneously, altered abundance of early regulators of HPC
      differentiation reveals a reduced functionality and a bias towards myeloid
      differentiation. Ageing causes alterations in the bone marrow niche too, and
      diminishes the functionality of the pathways involved in HPC homing. The data
      represent a valuable resource for further analyses, and for validation of
      knowledge gained from animal models.

PMID- 30275472
TI  - Reviewer recognition.
AB  - We would like to thank all those listed below for taking the time to review for
      Spinal Cord in 2017-your generosity is much appreciated and we hope your
      association with the journal continues in the future.

PMID- 30275471
TI  - Chromosome 4q25 Variant rs6817105 Bring Sinus Node Dysfunction and Left Atrial
      Enlargement.
AB  - Genome-wide association studies have reported a strong association of the single
      nucleotide polymorphism (SNP) rs6817105 (T > C) on chromosome 4q25 with atrial
      fibrillation (AF), but phenotype alterations conferred by this SNP have not been
      described. We genotyped SNP rs6817105 and examined the relationships among
      rs6817105 genotype, clinical characteristics, echocardiographic parameters, and
      electrophysiological parameters in 574 AF patients and 1,554 non-AF controls.
      Further, multiple microRNAs (miRNAs) are reported to be involved in atrial
      remodeling and AF pathogenesis, so we investigated relationships between
      rs6817105 genotype and serum concentrations of 2555 miRNAs. The rs6817105 minor
      allele frequency was significantly higher in AF patients than non-AF controls
      (66% vs. 47%, odds ratio 2.12, p = 4.9 * 10-26). Corrected sinus node recovery
      time (CSRT) was longer and left atrial volume index (LAVI) was larger in AF
      patients with the rs6817105 minor allele than patient non-carriers (CSRT: CC 557
      +/- 315 ms, CT 486 +/- 273 ms, TT 447 +/- 234 ms, p = 0.001; LAVI: CC 43.6 +/-
      12.1, CT 42.4 +/- 13.6, TT 39.8 +/- 11.6, p = 0.030). There were no significant
      differences between rs6817105 genotype and the serum concentrations of miRNAs.
      These findings strongly implicate rs6817105 minor allele in sinus node
      dysfunction and left atrial enlargement.

PMID- 30275473
TI  - Pastoralism may have delayed the end of the green Sahara.
AB  - The climate deterioration after the most recent African humid period (AHP) is a
      notable past example of desertification. Evidence points to a human population
      expansion in northern Africa prior to this, associated with the introduction of
      pastoralism. Here we consider the role, if any, of this population on the
      subsequent ecological collapse. Using a climate-vegetation model, we estimate the
      natural length of the most recent AHP. The model indicates that the system was
      most susceptible to collapse between 7 and 6 ka; at least 500 years before the
      observed collapse. This suggests that the inclusion of increasing elements of
      pastoralism was an effective adaptation to the regional environmental changes.
      Pastoralism also appears to have slowed the deterioration caused by orbitally
      driven climate change. This supports the view that modern pastoralism is not only
      sustainable, but beneficial for the management of the world's dryland
      environments.

PMID- 30275475
TI  - Lysosomal storage disorders.

PMID- 30275474
TI  - Ebola viral dynamics in nonhuman primates provides insights into virus immuno
      pathogenesis and antiviral strategies.
AB  - Despite several clinical trials implemented, no antiviral drug could demonstrate
      efficacy against Ebola virus. In non-human primates, early initiation of
      polymerase inhibitors favipiravir and remdesivir improves survival, but whether
      they could be effective in patients is unknown. Here we analyze the impact of
      antiviral therapy by using a mathematical model that integrates virological and
      immunological data of 44 cynomolgus macaques, left untreated or treated with
      favipiravir. We estimate that favipiravir has a ~50% efficacy in blocking viral
      production, which results in reducing virus growth and cytokine storm while
      IFNalpha reduces cell susceptibility to infection. Simulating the effect of
      delayed initiations of treatment, our model predicts survival rates of 60% for
      favipiravir and 100% for remdesivir when treatment is initiated within 3 and 4
      days post infection, respectively. These results improve the understanding of
      Ebola immuno-pathogenesis and can help optimize antiviral evaluation in future
      outbreaks.

PMID- 30275477
TI  - Author Correction: Meikin is a conserved regulator of meiosis-I-specific
      kinetochore function.
AB  - An Amendment to this Article has been published and is linked from the HTML
      version of this paper.

PMID- 30275476
TI  - Nearly all the sky is covered by Lyman-alpha emission around high-redshift
      galaxies.
AB  - Galaxies are surrounded by large reservoirs of gas, mostly hydrogen, that are fed
      by inflows from the intergalactic medium and by outflows from galactic winds.
      Absorption-line measurements along the lines of sight to bright and rare
      background quasars indicate that this circumgalactic medium extends far beyond
      the starlight seen in galaxies, but very little is known about its spatial
      distribution. The Lyman-alpha transition of atomic hydrogen at a wavelength of
      121.6 nanometres is an important tracer of warm (about 104 kelvin) gas in and
      around galaxies, especially at cosmological redshifts greater than about 1.6 at
      which the spectral line becomes observable from the ground. Tracing cosmic
      hydrogen through its Lyman-alpha emission has been a long-standing goal of
      observational astrophysics1-3, but the extremely low surface brightness of the
      spatially extended emission is a formidable obstacle. A new window into
      circumgalactic environments was recently opened by the discovery of ubiquitous
      extended Lyman-alpha emission from hydrogen around high-redshift galaxies4,5.
      Such measurements were previously limited to especially favourable systems6-8 or
      to the use of massive statistical averaging9,10 because of the faintness of this
      emission. Here we report observations of low-surface-brightness Lyman-alpha
      emission surrounding faint galaxies at redshifts between 3 and 6. We find that
      the projected sky coverage approaches 100 per cent. The corresponding rate of
      incidence (the mean number of Lyman-alpha emitters penetrated by any arbitrary
      line of sight) is well above unity and similar to the incidence rate of high
      column-density absorbers frequently detected in the spectra of distant quasars11
      14. This similarity suggests that most circumgalactic atomic hydrogen at these
      redshifts has now been detected in emission.

PMID- 30275478
TI  - Author Correction: Condensin association with histone H2A shapes mitotic
      chromosomes.
AB  - An Amendment to this Article has been published and is linked from the HTML
      version of this paper.

PMID- 30275479
TI  - Author Correction: Heterochromatin links to centromeric protection by recruiting
      shugoshin.
AB  - An Amendment to this Letter has been published and is linked from the HTML
      version of this paper.

PMID- 30275480
TI  - Author Correction: Global land change from 1982 to 2016.
AB  - In this Letter, errors in Supplementary Table 1 have been corrected.

PMID- 30275482
TI  - Abstracts from the 50th European Society of Human Genetics Conference: Program.

PMID- 30275483
TI  - Abstracts from the 50th European Society of Human Genetics Conference: Oral
      Presentations.

PMID- 30275481
TI  - Pilot study of expanded carrier screening for 11 recessive diseases in China:
      results from 10,476 ethnically diverse couples.
AB  - Expanded carrier screening (ECS) has been demonstrated to increase the detection
      rate of carriers compared with traditional tests. The aim of this study was to
      assess the potential value of ECS for clinical application in Southern China, a
      region with high prevalence of thalassemia and with diverse ethnic groups, and to
      provide a reference for future implementations in areas with similar population
      characteristics. A total of 10,476 prenatal/preconception couples from 34 self
      reported ethnic groups were simultaneously tested and analyzed anonymously for 11
      Mendelian disorders using targeted next-generation sequencing. Overall, 27.49% of
      individuals without self-reported family history of disorders were found to be
      carriers of at least 1 of the 11 conditions, and the carrier frequency varied
      greatly between ethnic groups, ranging from 4.15% to 81.35%. Furthermore, 255
      couples (2.43%) were identified as carrier couples at an elevated risk having an
      affected baby, sixty-five of which would not have been identified through the
      existing screening strategy, which only detects thalassemia. The modeled risk of
      fetuses being affected by any of the selected disorders was 531 per 100,000 (95%
      CI, 497-567 per 100,000). Our data demonstrate the feasibility of ECS, and
      provide evidence that ECS is a promising alternative to traditional one-condition
      screening strategies. The lessons learned from this experience should be
      applicable for other countries or regions with diverse ethnic groups.

PMID- 30275484
TI  - Abstracts from the 50th European Society of Human Genetics Conference: Electronic
      Posters.

PMID- 30275485
TI  - Abstracts from the 50th European Society of Human Genetics Conference: Posters.

PMID- 30275486
TI  - European guidelines for constitutional cytogenomic analysis.
AB  - With advancing technology and the consequent shift towards an increasing
      application of molecular genetic techniques (e.g., microarrays, next-generation
      sequencing) with the potential for higher resolution in specific contexts, as
      well as the application of combined testing strategies for the diagnosis of
      chromosomal disorders, it is crucial that cytogenetic/cytogenomic services keep
      up to date with technology and have documents that provide guidance in this
      constantly evolving scenario. These new guidelines therefore aim to provide an
      updated, practical and easily available document that will enable genetic
      laboratories to operate within acceptable standards and to maintain a quality
      service.

PMID- 30275487
TI  - Distribution and phylogenetics of whiteflies and their endosymbiont relationships
      after the Mediterranean species invasion in Brazil.
AB  - The Bemisia tabaci is a polyphagous insect and a successful vector of plant
      viruses. B. tabaci is a species complex and in Brazil native species from the New
      World (NW) group, as well as the invasive species, Middle East-Asia Minor 1
      (MEAM1) and Mediterranean (MED) were reported. For better understanding the
      distribution of the different species four years after the Mediterranean species
      invasion in Brazil, whiteflies were collected from 237 locations throughout the
      country between the years of 2013 and 2017, species were identified and the
      facultative endosymbionts detected. The survey revealed that MEAM1 was the
      prevalent species found on major crops across Brazil. It is the only species
      present in North, Northwestern and Central Brazil and was associated with virus
      infected plants. MED was found in five States from Southeast to South regions,
      infesting mainly ornamental plants and was not associated with virus-infected
      plants. The prevalent endosymbionts identified in MEAM1 were Hamiltonella and
      Rickettsia; and the mtCOI analysis revealed low genetic diversity for MEAM1. In
      contrast, several different endosymbionts were identified in MED including
      Hamiltonella, Rickettsia, Wolbachia and Arsenophonus; and two distinct genetic
      groups were found based on the mtCOI analysis. Monitoring the distribution of the
      whiteflies species in Brazil is essential for proper management of this pest.

PMID- 30275488
TI  - Experimental evidence for the enhanced and reduced stopping regimes for protons
      propagating through hot plasmas.
AB  - Our understanding of the dynamics of ion collisional energy loss in a plasma is
      still not complete, in part due to the difficulty and lack of high-quality
      experimental measurements. These measurements are crucial to benchmark existing
      models. Here, we show that such a measurement is possible using high-flux proton
      beams accelerated by high intensity short pulse lasers, where there is a high
      number of particles in a picosecond pulse, which is ideal for measurements in
      quickly expanding plasmas. By reducing the energy bandwidth of the protons using
      a passive selector, we have made proton stopping measurements in partially
      ionized Argon and fully ionized Hydrogen plasmas with electron temperatures of
      hundreds of eV and densities in the range 1020-1021 cm-3. In the first case, we
      have observed, consistently with previous reports, enhanced stopping of protons
      when compared to stopping power in non-ionized gas. In the second case, we have
      observed for the first time the regime of reduced stopping, which is
      theoretically predicted in such hot and fully ionized plasma. The versatility of
      these tunable short-pulse laser based ion sources, where the ion type and energy
      can be changed at will, could open up the possibility for a variety of ion
      stopping power measurements in plasmas so long as they are well characterized in
      terms of temperature and density. In turn, these measurements will allow tests of
      the validity of existing theoretical models.

PMID- 30275489
TI  - Metabolic profiling of metformin treatment for low-level Pb-induced
      nephrotoxicity in rat urine.
AB  - Chronic kidney disease is a worldwide problem, and Pb contamination is a
      potential risk factor. Since current biomarkers are not sensitive for the
      diagnosis of Pb-induced nephrotoxicity, novel biomarkers are needed. Metformin
      has both hypoglycaemic effects and reno-protection ability. However, its
      mechanism of action is unknown. We aimed to discover the early biomarkers for the
      diagnosis of low-level Pb-induced nephrotoxicity and understand the mechanism of
      reno-protection of metformin. Male Wistar rats were randomly divided into
      control, Pb, Pb + ML, Pb + MH and MH groups. Pb (250 ppm) was given daily via
      drinking water. Metformin (50 or 100 mg/kg/d) was orally administered. Urine was
      analysed by nuclear magnetic resonance (NMR)-based metabolomics coupled with
      multivariate statistical analysis, and potential biomarkers were subsequently
      quantified. The results showed that Pb-induced nephrotoxicity was closely
      correlated with the elevation of 5-aminolevulinic acid, D-lactate and
      guanidinoacetic acid in urine. After co-treatment with metformin, 5
      aminolevulinic acid and D-lactate were decreased. This is the first demonstration
      that urinary 5-aminolevulinic acid, D-lactate and guanidinoacetic acid could be
      early biomarkers of low-level Pb-induced nephrotoxicity in rats. The reno
      protection of metformin might be attributable to the reduction of D-lactate
      excretion.

PMID- 30275491
TI  - Publisher Correction: A novel two-score system for interferon status segregates
      autoimmune diseases and correlates with clinical features.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30275492
TI  - Extensive Vibrational Characterisation and Long-Term Monitoring of Honeybee Dorso
      Ventral Abdominal Vibration signals.
AB  - A very common honeybee signal is the dorso-ventral abdominal vibration (DVAV)
      signal, widely accepted as a modulatory signal meaning: "prepare for greater
      activity". In this study, using ultra-sensitive accelerometer technology embedded
      in the honeycomb, we visually confirm the one-to-one relationship between a DVAV
      signal being produced and the resulting accelerometer waveform, allowing the
      measurement of DVAV signals without relying on any visual inspection. We then
      demonstrate a novel method for the continuous in-situ non-invasive automated
      monitoring of this honeybee signal, not previously known to induce any vibration
      into the honeycomb, and most often inaudible to human hearing. We monitored a
      total of three hives in the UK and France, showing that the signal is very
      common, highly repeatable and occurs more frequently at night, exhibiting a
      distinct decrease in instances and increase in amplitude towards mid-afternoon.
      We also show an unprecedented increase in the cumulative amplitude of DVAV
      signals occurring in the hours preceding and following a primary swarm. We
      conclude that DVAV signals may have additional functions beyond solely being a
      foraging activation signal, and that the amplitude of the signal might be
      indicative of the switching of its purpose.

PMID- 30275494
TI  - Intracellular gold nanoclusters boost energy conversion.

PMID- 30275493
TI  - Discrete Hall resistivity contribution from Neel skyrmions in multilayer
      nanodiscs.
AB  - Magnetic skyrmions are knot-like quasiparticles. They are candidates for non
      volatile data storage in which information is moved between fixed read and write
      terminals. The read-out operation of skyrmion-based spintronic devices will rely
      on the electrical detection of a single magnetic skyrmion within a nanostructure.
      Here we present Pt/Co/Ir nanodiscs that support skyrmions at room temperature. We
      measured the Hall resistivity and simultaneously imaged the spin texture using
      magnetic scanning transmission X-ray microscopy. The Hall resistivity is
      correlated to both the presence and size of the skyrmion. The size-dependent part
      matches the expected anomalous Hall signal when averaging the magnetization over
      the entire disc. We observed a resistivity contribution that only depends on the
      number and sign of skyrmion-like objects present in the disc. Each skyrmion gives
      rise to 22 +/- 2 nOmega cm irrespective of its size. This contribution needs to
      be considered in all-electrical detection schemes applied to skyrmion-based
      devices. Not only the area of Neel skyrmions but also their number and sign
      contribute to their Hall resistivity.

PMID- 30275495
TI  - Bacteria photosensitized by intracellular gold nanoclusters for solar fuel
      production.
AB  - The demand for renewable and sustainable fuel has prompted the rapid development
      of advanced nanotechnologies to effectively harness solar power. The construction
      of photosynthetic biohybrid systems (PBSs) aims to link preassembled biosynthetic
      pathways with inorganic light absorbers. This strategy inherits both the high
      light-harvesting efficiency of solid-state semiconductors and the superior
      catalytic performance of whole-cell microorganisms. Here, we introduce an
      intracellular, biocompatible light absorber, in the form of gold nanoclusters
      (AuNCs), to circumvent the sluggish kinetics of electron transfer for existing
      PBSs. Translocation of these AuNCs into non-photosynthetic bacteria enables
      photosynthesis of acetic acid from CO2. The AuNCs also serve as inhibitors of
      reactive oxygen species (ROS) to maintain high bacterium viability. With the dual
      advantages of light absorption and biocompatibility, this new generation of PBS
      can efficiently harvest sunlight and transfer photogenerated electrons to
      cellular metabolism, realizing CO2 fixation continuously over several days.

PMID- 30275490
TI  - Genome-wide discovery of somatic regulatory variants in diffuse large B-cell
      lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from
      mature B-cells. Prognosis is strongly associated with molecular subgroup,
      although the driver mutations that distinguish the two main subgroups remain
      poorly defined. Through an integrative analysis of whole genomes, exomes, and
      transcriptomes, we have uncovered genes and non-coding loci that are commonly
      mutated in DLBCL. Our analysis has identified novel cis-regulatory sites, and
      implicates recurrent mutations in the 3' UTR of NFKBIZ as a novel mechanism of
      oncogene deregulation and NF-kappaB pathway activation in the activated B-cell
      (ABC) subgroup. Small amplifications associated with over-expression of FCGR2B
      (the Fcgamma receptor protein IIB), primarily in the germinal centre B-cell (GCB)
      subgroup, correlate with poor patient outcomes suggestive of a novel oncogene.
      These results expand the list of subgroup driver mutations that may facilitate
      implementation of improved diagnostic assays and could offer new avenues for the
      development of targeted therapeutics.

PMID- 30275496
TI  - The prevalence of olfactory- versus visual-signal encounter by searching
      bumblebees.
AB  - While the phrase 'foraging bumblebee' brings to mind a bumbling bee flying flower
      to flower in a sunny meadow, foraging is a complicated series of behaviors such
      as: locating a floral patch; selecting a flower-type; learning handling skills
      for pollen and nectar extraction; determining when to move-on from a patch;
      learning within-patch paths (traplining); and learning efficient hive-to-patch
      routes (spatial navigation). Thus the term 'forager' encompasses multiple
      distinct behaviors that rely on different sensory modalities. Despite a robust
      literature on bumblebee foraging behavior, few studies are directly relevant to
      sensory-guided search; i.e. how workers locate novel patches. The first step in
      answering this question is to determine what sensory information is available to
      searching bumblebees. This manuscript presents a computational model that
      elucidates the relative frequency of visual and olfactory cues that are available
      to workers searching for floral resources under a range of ecologically relevant
      scenarios. Model results indicate that odor is the most common sensory cue
      encountered during search flights. When the likelihood of odor-plume contact is
      higher, odor-encounter is ubiquitous. While integrative (visual + olfactory) cues
      are common when foragers are searching for larger flowers (e.g. Echinacea), they
      become rare when foragers are searching for small flowers (e.g. Penstemon).
      Visual cues are only encountered in isolation when foragers are seeking large
      flowers with a low odor-plume contact probability. These results indicate that
      despite the multisensory nature of floral signals, different modalities may be
      encountered in isolation during search-behavior, as opposed to the reliably
      multimodal signals encountered during patch-exploitation or nectar/ pollen
      acquisition.

PMID- 30275498
TI  - Digital coding of mechanical stress in a dynamic covalent shape memory polymer
      network.
AB  - Controlling stresses in materials presents many unusual opportunities for their
      engineering applications. The potential for current approaches is severely
      limited by the intrinsic tie between the stress and the geometric shape. Here, we
      report a material concept that allows stress management in a highly efficient
      digital manner while decoupling the stress and the geometric shape. This is
      realized in a dynamic covalent shape memory polymer network, for which the
      elastic shape memory sets the baseline stress level and maintains the geometric
      shape while the plasticity enabled by the dynamic bond exchange allows stress
      tuning. With a digital gray scale photothermal mechanism, any arbitrarily defined
      stress distribution can be created in a free-standing polymer film. The naturally
      invisible stresses can be further visualized as mechanical colors under polarized
      light, revealing its potential for encoding hidden information. Our approach
      expands the technological potential in many areas for which stresses are
      relevant.

PMID- 30275497
TI  - Regulatory control of DNA end resection by Sae2 phosphorylation.
AB  - DNA end resection plays a critical function in DNA double-strand break repair
      pathway choice. Resected DNA ends are refractory to end-joining mechanisms and
      are instead channeled to homology-directed repair. Using biochemical, genetic,
      and imaging methods, we show that phosphorylation of Saccharomyces cerevisiae
      Sae2 controls its capacity to promote the Mre11-Rad50-Xrs2 (MRX) nuclease to
      initiate resection of blocked DNA ends by at least two distinct mechanisms.
      First, DNA damage and cell cycle-dependent phosphorylation leads to Sae2
      tetramerization. Second, and independently, phosphorylation of the conserved C
      terminal domain of Sae2 is a prerequisite for its physical interaction with
      Rad50, which is also crucial to promote the MRX endonuclease. The lack of this
      interaction explains the phenotype of rad50S mutants defective in the processing
      of Spo11-bound DNA ends during meiotic recombination. Our results define how
      phosphorylation controls the initiation of DNA end resection and therefore the
      choice between the key DNA double-strand break repair mechanisms.

PMID- 30275499
TI  - Cognitive dysfunction in atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common arrhythmia in adults, and its
      incidence and prevalence increase with age. The risk of cognitive impairment and
      dementia also increases with age, and both AF and cognitive impairment or
      dementia share important risk factors. In meta-analyses of published studies, AF
      is associated with a 2.4-fold and 1.4-fold increase in the risk of dementia in
      patients with or without a history of stroke, respectively. This association is
      independent of shared risk factors such as hypertension and diabetes mellitus.
      Neuroimaging has illustrated several potential mechanisms of cognitive decline in
      patients with AF. AF is associated with increased prevalence of silent cerebral
      infarcts, and more recent data also suggest an increased prevalence of cerebral
      microbleeds with AF. AF is also associated with a pro-inflammatory state, and the
      relationship between AF-induced systemic inflammation and dementia remains to be
      investigated. Preliminary reports indicate that anticoagulation medication
      including warfarin can reduce the risk of cognitive impairment in patients with
      AF. Catheter ablation, increasingly used to maintain sinus rhythm in patients
      with AF, is associated with the formation of new silent cerebral lesions. The
      majority of these lesions are not detectable after 1 year, and insufficient data
      are available to evaluate their effect on cognition. Large prospective studies
      are urgently needed to confirm the association between AF and dementia, to
      elucidate the associated mechanisms, and to investigate the effect of
      anticoagulation and rhythm control on cognition.

PMID- 30275501
TI  - Tunable phonon blockade in weakly nonlinear coupled mechanical resonators via
      Coulomb interaction.
AB  - Realizing quantum mechanical behavior in micro- and nanomechanical resonators has
      attracted continuous research effort. One of the ways for observing quantum
      nature of mechanical objects is via the mechanism of phonon blockade. Here, we
      show that phonon blockade could be achieved in a system of two weakly nonlinear
      mechanical resonators coupled by a Coulomb interaction. The optimal blockade
      arises as a result of the destructive quantum interference between paths leading
      to two-phonon excitation. It is observed that, in comparison to a single drive
      applied on one mechanical resonator, driving both the resonators can be
      beneficial in many aspects; such as, in terms of the temperature sensitivity of
      phonon blockade and also with regard to the tunability, by controlling the
      amplitude and the phase of the second drive externally. We also show that via a
      radiation pressure induced coupling in an optomechanical cavity, phonon
      correlations can be measured indirectly in terms of photon correlations of the
      cavity mode.

PMID- 30275500
TI  - Elucidating a role for the cytoplasmic domain in the Mycobacterium tuberculosis
      mechanosensitive channel of large conductance.
AB  - Microbial survival in dynamic environments requires the ability to successfully
      respond to abrupt changes in osmolarity. The mechanosensitive channel of large
      conductance (MscL) is a ubiquitous channel that facilitates the survival of
      bacteria and archaea under severe osmotic downshock conditions by relieving
      excess turgor pressure in response to increased membrane tension. A prominent
      structural feature of MscL, the cytoplasmic C-terminal domain, has been suggested
      to influence channel assembly and function. In this report, we describe the X-ray
      crystal structure and electrophysiological properties of a C-terminal domain
      truncation of the Mycobacterium tuberculosis MscL (MtMscLDeltaC). A crystal
      structure of MtMscLDeltaC solubilized in the detergent n-dodecyl-beta-D
      maltopyranoside reveals the pentameric, closed state-like architecture for the
      membrane spanning region observed in the previously solved full-length MtMscL.
      Electrophysiological characterization demonstrates that MtMscLDeltaC retains
      mechanosensitivity, but with conductance and tension sensitivity more closely
      resembling full length EcMscL than MtMscL. This study establishes that the C
      terminal domain of MtMscL is not required for oligomerization of the full-length
      channel, but rather influences the tension sensitivity and conductance properties
      of the channel. The collective picture that emerges from these data is that each
      MscL channel structure has characteristic features, highlighting the importance
      of studying multiple homologs.

PMID- 30275502
TI  - A quantitative study on growth variability and production of ochratoxin A and its
      derivatives by A. carbonarius and A. niger in grape-based medium.
AB  - Aspergillus carbonarius and Aspergillus niger are the main responsible fungi for
      the accumulation of ochratoxin A (OTA) in wine grapes. Some strains are able to
      convert the parent mycotoxin into other compounds by means of hydrolysis and/or
      conjugation reactions through their defense mechanisms and enzymatic activity,
      leading to the formation of a modified mycotoxin. Thus, the variability of growth
      and metabolite production are inherent to the strain, occurring distinctively
      even when submitted to similar conditions. In this sense, this contribution aimed
      at determining the variability in multiplication and production of OTA by strains
      of A. carbonarius and A. niger isolated from grapes, as well as investigating the
      formation of modified mycotoxins. Strains were incubated in grape-based medium,
      and the diameter of the colonies measured daily. The determination of OTA was
      performed by high-performance liquid chromatography and the identification of
      modified mycotoxins was carried out using high-resolution mass spectrometry.
      Variabilities in terms of growth and OTA production were assessed across five
      different strains. Peak production of OTA was detected on day 15, and a decline
      on day 21 was observed, indicating that the observed reduction may be associated
      with the degradation or modification of the OTA over time by the fungus.
      Ethylamide ochratoxin A, a modified mycotoxin identified in this study, provides
      evidence that there may be underreporting of total mycotoxin levels in food,
      increasing uncertainty concerning health risks to the population.

PMID- 30275503
TI  - Hypertrophic cardiomyopathy disease results from disparate impairments of cardiac
      myosin function and auto-inhibition.
AB  - Hypertrophic cardiomyopathies (HCM) result from distinct single-point mutations
      in sarcomeric proteins that lead to muscle hypercontractility. While different
      models account for a pathological increase in the power output, clear
      understanding of the molecular basis of dysfunction in HCM is the mandatory next
      step to improve current treatments. Here, we present an optimized quasi-atomic
      model of the sequestered state of cardiac myosin coupled to X-ray crystallography
      and in silico analysis of the mechanical compliance of the lever arm, allowing
      the systematic study of a large set of HCM mutations and the definition of
      different mutation classes based on their effects on lever arm compliance,
      sequestered state stability, and motor functions. The present work reconciles
      previous models and explains how distinct HCM mutations can have disparate
      effects on the motor mechano-chemical parameters and yet lead to the same
      disease. The framework presented here can guide future investigations aiming at
      finding HCM treatments.

PMID- 30275504
TI  - Relationship between mean platelet volume and metabolic syndrome in Chinese
      patients.
AB  - Mean platelet volume (MPV) is a determinant of activation and variability of
      platelets (PLT). The focus of this study was to to investigate MPV values in
      patients with and without metabolic syndrome (MS). It also evaluates the
      association between them. There are close connections among MPV, MS, and
      cardiometabolic risk. We compiled age, body mass index, blood cell counts, MPV,
      and other data of 59976 self-reported healthy volunteers (28428 male, 31548
      female), 24.65% of who have MS. The mean age of the group was 48.21 years old.
      The data was grouped by sex and values of data between men and women groups were
      analyzed by independent sample's t-test. The relationship between sex and MS was
      evaluated by chi-square tests. Crude odd ratios of MS between MPV quartiles and
      95% confidence intervals were analyzed by binary logistic regression in this
      study. We found women had higher levels of MPV (10.09 vs. 9.98, P < 0.01) and PLT
      (228.68 vs. 212.11, P < 0.01) than men. In females, the prevalence of MS was
      higher in low MPV group than in high MPV groups. The odds of having MS were
      significantly lower in higher MPV quartiles compared with MPV Quartile 1 in women
      (Adjusted OR < 1, P < 0.01). This study indicated that MS was inversely
      associated with MPV in females only.

PMID- 30275506
TI  - Superoxide dismutase activity enabled by a redox-active ligand rather than metal.
AB  - Reactive oxygen species are integral to many physiological processes. Although
      their roles are still being elucidated, they seem to be linked to a variety of
      disorders and may represent promising drug targets. Mimics of superoxide
      dismutases, which catalyse the decomposition of O2*- to H2O2 and O2, have
      traditionally used redox-active metals, which are toxic outside of a tightly
      coordinating ligand. Purely organic antioxidants have also been investigated but
      generally require stoichiometric, rather than catalytic, doses. Here, we show
      that a complex of the redox-inactive metal zinc(II) with a hexadentate ligand
      containing a redox-active quinol can catalytically degrade superoxide, as
      demonstrated by both reactivity assays and stopped-flow kinetics studies of
      direct reactions with O2*- and the zinc(II) complex. The observed superoxide
      dismutase catalysis has an important advantage over previously reported work in
      that it is hastened, rather than impeded, by the presence of phosphate, the
      concentration of which is high under physiological conditions.

PMID- 30275507
TI  - Sulfone-containing covalent organic frameworks for photocatalytic hydrogen
      evolution from water.
AB  - Nature uses organic molecules for light harvesting and photosynthesis, but most
      man-made water splitting catalysts are inorganic semiconductors. Organic
      photocatalysts, while attractive because of their synthetic tunability, tend to
      have low quantum efficiencies for water splitting. Here we present a crystalline
      covalent organic framework (COF) based on a benzo-bis(benzothiophene sulfone)
      moiety that shows a much higher activity for photochemical hydrogen evolution
      than its amorphous or semicrystalline counterparts. The COF is stable under long
      term visible irradiation and shows steady photochemical hydrogen evolution with a
      sacrificial electron donor for at least 50 hours. We attribute the high quantum
      efficiency of fused-sulfone-COF to its crystallinity, its strong visible light
      absorption, and its wettable, hydrophilic 3.2 nm mesopores. These pores allow the
      framework to be dye-sensitized, leading to a further 61% enhancement in the
      hydrogen evolution rate up to 16.3 mmol g-1 h-1. The COF also retained its
      photocatalytic activity when cast as a thin film onto a support.

PMID- 30275505
TI  - High Expression of EpCAM and Sox2 is a Positive Prognosticator of Clinical
      Outcome for Head and Neck Carcinoma.
AB  - Locally advanced head and neck squamous cell carcinomas (HNSCC) have limited
      prognosis due to frequent treatment failure. Currently, TNM-classification and
      human papillomavirus (HPV) infection are the sole clinical prognosticators of
      outcome. Tumor heterogeneity and stemness based on epithelial-mesenchymal
      transition reportedly associate with therapy resistance. The capacity of
      epithelial marker EpCAM (EpEX), stemness regulator Sox2 and mesenchymal marker
      vimentin to predict clinical outcome of HSNCC patients was assessed upon
      immunohistochemistry staining in two cohorts of HNSCC patients treated with
      surgery and adjuvant radio (chemo) therapy (n = 94) and primary radio (chemo)
      therapy (n = 94), respectively. Prognostic values with respect to overall,
      disease-free and disease-specific survival were assessed in uni- and multivariate
      cox proportional hazard models to generate integrated risk scores. EpEX, Sox2 and
      vimentin displayed substantial inter- and intratumoral heterogeneity. EpEXhigh
      and Sox2high predicted improved clinical outcome in the discovery cohort and in
      the HPV-negative sub-cohort. EpEXhigh and Sox2high were confirmed as
      prognosticators of clinical outcome in the validation cohort treated with
      definitive radio(chemo)therapy. Importantly, EpEXhigh identified patients with
      improved survival within the HPV-negative subgroup of the validation cohort.
      Hence, Sox2high and particularly EpEXhigh have potential as tools to predict
      clinical performance of HNSCC patients, foremost HPV-negative cases, in the frame
      of molecular-guided treatment decision-making.

PMID- 30275508
TI  - Genetic structure and polymorphisms of Gelao ethnicity residing in southwest
      china revealed by X-chromosomal genetic markers.
AB  - X-chromosome short tandem repeat markers (X-STRs), due to their special
      inheritance models, physical location on a single chromosome and the absence of
      recombination in male meiosis, play an important role in forensic and population
      genetics. While a series of genetic analyses focusing on the genetic diversity
      and forensic characteristics of X-STRs are well studied for
      ethnically/linguistically diverse and demographically large Chinese populations,
      genetic evidence from Gelao ethnicity is still sparse. Here, we genotyped the
      first batch of 19 X-STRs in 513 Chinese Gelao individuals (265 females and 248
      males), and reported genetic polymorphisms, forensic characteristics based on the
      single locus and seven linkage groups. DXS10135 with the highest PIC (0.9106) and
      LG1 (DXS10148-DXS10135-DXS8378) with the largest HD (0.9970) are polymorphic and
      informative. The CPDs in Gelao males and females are respectively larger than
      0.999999999997095 and 0.99999999999999999999918, and the combined MECs are larger
      than 0.999999975715109. Subsequently, we investigated the population
      relationships among 14 Chinese populations based on 19 X-STRs and among 23
      populations based on 11 overlapped X-STRs. Our results revealed genetic
      differentiations among Tibeto-Burman, Altaic and other Chinese homogenous
      populations, and demonstrated that Guizhou Gelao has the genetically closer
      relationships with Han Chinese and geographically close Guizhou Miao.

PMID- 30275509
TI  - Calcium increases titin N2A binding to F-actin and regulated thin filaments.
AB  - Mutations in titin are responsible for many cardiac and muscle diseases, yet the
      underlying mechanisms remain largely unexplained. Numerous studies have
      established roles for titin in muscle function, and Ca2+-dependent interactions
      between titin and actin have been suggested to play a role in muscle contraction.
      The present study used co-sedimentation assays, dynamic force spectroscopy (DFS),
      and in vitro motility (IVM) assays to determine whether the N2A region of titin,
      overlooked in previous studies, interacts with actin in the presence of Ca2+. Co
      sedimentation demonstrated that N2A - F-actin binding increases with increasing
      protein and Ca2+ concentration, DFS demonstrated increased rupture forces and
      decreased koff in the presence of Ca2+, and IVM demonstrated a Ca2+-dependent
      reduction in motility of F-actin and reconstituted thin filaments in the presence
      of N2A. These results indicate that Ca2+ increases the strength and stability of
      N2A - actin interactions, supporting the hypothesis that titin plays a regulatory
      role in muscle contraction. The results further support a model in which N2A -
      actin binding in active muscle increases titin stiffness, and that impairment of
      this mechanism contributes to the phenotype in muscular dystrophy with myositis.
      Future studies are required to determine whether titin - actin binding occurs in
      skeletal muscle sarcomeres in vivo.

PMID- 30275512
TI  - Anaerobic nitrate reduction divergently governs population expansion of the
      enteropathogen Vibrio cholerae.
AB  - To survive and proliferate in the absence of oxygen, many enteric pathogens can
      undergo anaerobic respiration within the host by using nitrate (NO3-) as an
      electron acceptor1,2. In these bacteria, NO3- is typically reduced by a nitrate
      reductase to nitrite (NO2-), a toxic intermediate that is further reduced by a
      nitrite reductase3. However, Vibrio cholerae, the intestinal pathogen that causes
      cholera, lacks a nitrite reductase, leading to NO2- accumulation during nitrate
      reduction4. Thus, V. cholerae is thought to be unable to undergo NO3--dependent
      anaerobic respiration4. Here, we show that during hypoxic growth, NO3- reduction
      in V. cholerae divergently affects bacterial fitness in a manner dependent on
      environmental pH. Remarkably, in alkaline conditions, V. cholerae can reduce NO3-
      to support population growth. Conversely, in acidic conditions, accumulation of
      NO2- from NO3- reduction simultaneously limits population expansion and preserves
      cell viability by lowering fermentative acid production. Interestingly, other
      bacterial species such as Salmonella typhimurium, enterohaemorrhagic Escherichia
      coli (EHEC) and Citrobacter rodentium also reproduced this pH-dependent response,
      suggesting that this mechanism might be conserved within enteric pathogens. Our
      findings explain how a bacterial pathogen can use a single redox reaction to
      divergently regulate population expansion depending on the fluctuating
      environmental pH.

PMID- 30275510
TI  - Correction: Expanding the clinical phenotype of individuals with a 3-bp in-frame
      deletion of the NF1 gene (c.2970_2972del): an update of genotype-phenotype
      correlation.
AB  - A correction has been published to this Article. The PDF and HTML have been
      updated accordingly.

PMID- 30275513
TI  - In vivo TssA proximity labelling during type VI secretion biogenesis reveals TagA
      as a protein that stops and holds the sheath.
AB  - The type VI secretion system (T6SS) is a multiprotein weapon used by bacteria to
      destroy competitor cells. The T6SS contractile sheath wraps an effector-loaded
      syringe that is injected into the target cell. This tail structure assembles onto
      the baseplate that is docked to the membrane complex. In enteroaggregative
      Escherichia coli, TssA plays a central role at each stage of the T6SS assembly
      pathway by stabilizing the baseplate and coordinating the polymerization of the
      tail. Here we adapted an assay based on APEX2-dependent biotinylation to identify
      the proximity partners of TssA in vivo. By using stage-blocking mutations, we
      define the temporal contacts of TssA during T6SS biogenesis. This proteomic
      mapping approach also revealed an additional partner of TssA, TagA. We show that
      TagA is a cytosolic protein tightly associated with the membrane. Analyses of
      sheath dynamics further demonstrate that TagA captures the distal end of the
      sheath to stop its polymerization and to maintain it under the extended
      conformation.

PMID- 30275511
TI  - Structural basis for usher activation and intramolecular subunit transfer in P
      pilus biogenesis in Escherichia coli.
AB  - Chaperone-usher pathway pili are extracellular proteinaceous fibres ubiquitously
      found on Gram-negative bacteria, and mediate host-pathogen interactions and
      biofilm formation critical in pathogenesis in numerous human diseases1. During
      pilus assembly, an outer membrane macromolecular machine called the usher
      catalyses pilus biogenesis from the individual subunits that are delivered as
      chaperone-subunit complexes in the periplasm. The usher orchestrates pilus
      assembly using all five functional domains: a 24-stranded transmembrane beta
      barrel translocation domain, a beta-sandwich plug domain, an amino-terminal
      periplasmic domain and two carboxy-terminal periplasmic domains (CTD1 and CTD2)2
      6. Despite extensive structural and functional characterization, the mechanism by
      which the usher is activated to initiate pilus biogenesis is unknown. Here, we
      present the crystal structure of the full-length PapC usher from Escherichia coli
      in complex with its cognate PapDG chaperone-subunit complex in a pre-activation
      state, elucidating molecular details of how the usher is specifically engaged by
      allosteric interactions with its substrate preceding activation and how the usher
      facilitates the transfer of subunits from the amino-terminal periplasmic domain
      to the CTDs during pilus assembly. This work elucidates the intricate workings of
      a molecular machine that catalyses chaperone-usher pathway pilus assembly and
      opens the door for the development of potent inhibitors to block pilus
      biogenesis.

PMID- 30275514
TI  - Accelerating anticancer drug development - opportunities and trade-offs.
AB  - The traditional approach to drug development in oncology, with discrete phases of
      clinical testing, is becoming untenable owing to expansion of the precision
      medicine paradigm, whereby patients are stratified into multiple subgroups
      according to the underlying cancer biology. Seamless approaches to drug
      development in oncology hold great promise of accelerating the accessibility of
      novel therapeutic agents to the public but are also accompanied by important
      trade-offs, including the limited availability of information on the clinical
      benefit and safety of novel agents at the time of market entry. In this
      Perspectives article, we describe several opportunities, in the form of novel
      trial designs or modelling strategies, to improve the efficiency of drug
      development in oncology, as well as new mechanisms to obtain information about
      anticancer therapies throughout their life cycle, such as innovative functional
      imaging techniques or the use of real-world clinical data.

PMID- 30275515
TI  - Therapeutic strategies to target RAS-mutant cancers.
AB  - RAS genes are the most commonly mutated oncogenes in cancer, but effective
      therapeutic strategies to target RAS-mutant cancers have proved elusive. A key
      aspect of this challenge is the fact that direct inhibition of RAS proteins has
      proved difficult, leading researchers to test numerous alternative strategies
      aimed at exploiting RAS-related vulnerabilities or targeting RAS effectors. In
      the past few years, we have witnessed renewed efforts to target RAS directly,
      with several promising strategies being tested in clinical trials at different
      stages of completion. Important advances have also been made in approaches
      designed to indirectly target RAS by improving inhibition of RAS effectors,
      exploiting synthetic lethal interactions or metabolic dependencies, using
      therapeutic combination strategies or harnessing the immune system. In this
      Review, we describe historical and ongoing efforts to target RAS-mutant cancers
      and outline the current therapeutic landscape in the collective quest to overcome
      the effects of this crucial oncogene.

PMID- 30275517
TI  - NMD-degradome sequencing reveals ribosome-bound intermediates with 3'-end non
      templated nucleotides.
AB  - Nonsense-mediated messenger RNA decay (NMD) controls mRNA quality and degrades
      physiologic mRNAs to fine-tune gene expression in changing developmental or
      environmental milieus. NMD requires that its targets are removed from the
      translating pool of mRNAs. Since the decay steps of mammalian NMD remain unknown,
      we developed assays to isolate and sequence direct NMD decay intermediates
      transcriptome-wide based on their co-immunoprecipitation with phosphorylated
      UPF1, which is the active form of this essential NMD factor. We show that, unlike
      steady-state UPF1, phosphorylated UPF1 binds predominantly deadenylated mRNA
      decay intermediates and activates NMD cooperatively from 5'- and 3'-ends. We
      leverage method modifications to characterize the 3'-ends of NMD decay
      intermediates, show that they are ribosome-bound, and reveal that some are
      subject to the addition of non-templated nucleotide. Uridines are added by TUT4
      and TUT7 terminal uridylyl transferases and removed by the Perlman syndrome
      associated exonuclease DIS3L2. The addition of other non-templated nucleotides
      appears to inhibit decay.

PMID- 30275516
TI  - DNA G-quadruplex structures mold the DNA methylome.
AB  - Control of DNA methylation level is critical for gene regulation, and the factors
      that govern hypomethylation at CpG islands (CGIs) are still being uncovered.
      Here, we provide evidence that G-quadruplex (G4) DNA secondary structures are
      genomic features that influence methylation at CGIs. We show that the presence of
      G4 structure is tightly associated with CGI hypomethylation in the human genome.
      Surprisingly, we find that these G4 sites are enriched for DNA methyltransferase
      1 (DNMT1) occupancy, which is consistent with our biophysical observations that
      DNMT1 exhibits higher binding affinity for G4s as compared to duplex, hemi
      methylated, or single-stranded DNA. The biochemical assays also show that the G4
      structure itself, rather than sequence, inhibits DNMT1 enzymatic activity. Based
      on these data, we propose that G4 formation sequesters DNMT1 thereby protecting
      certain CGIs from methylation and inhibiting local methylation.

PMID- 30275520
TI  - Making matters worse.

PMID- 30275518
TI  - Leukocyte telomere length and risk of gastric cardia adenocarcinoma.
AB  - As a chromosome stabilizer, telomeres play an essential part in maintaining the
      stability and integrity of human genome. Shortened telomeres have been associated
      with the development of cancers but it is still largely unclear whether leukocyte
      telomere length contributes to predisposition of gastric cardia adenocarcinoma
      (GCA). We conducted a case-control study consisting of 524 GCA cases and 510
      controls to assess the association between telomere length in peripheral blood
      leukocytes and GCA risk in a Chinese Han population. The GCA patients had
      significantly overall shorter relative leukocyte telomere length (RTL) (median +/
      SD: 1.10 +/- 0.54) when compared with the controls (1.24 +/- 0.58). Individuals
      with the shortest quartile of RTL performed a doubled GCA risk (OR = 2.18; 95% CI
      = 1.47-3.22, P = 9.90 * 10-5) when compared with those with the highest quartile.
      We also found that telomere shortening and smoking have a significantly
      synergistic effect in intensifying risk of GCA (OR = 7.03, 95% CI = 4.55-10.86, P
      = 1.43 * 10-18). These findings indicate that short RTL contributes to increased
      susceptibility of gastric cardia adenocarcinoma and might be a promising marker
      to identify high-risk individuals combined with lifestyle risk factors.

PMID- 30275519
TI  - Competition and dual users in complex contagion processes.
AB  - We study the competition of two spreading entities, for example innovations, in
      complex contagion processes in complex networks. We develop an analytical
      framework and examine the role of dual users, i.e. agents using both
      technologies. Searching for the spreading transition of the new innovation and
      the extinction transition of a preexisting one, we identify different phases
      depending on network mean degree, prevalence of preexisting technology, and
      thresholds of the contagion process. Competition with the preexisting technology
      effectively suppresses the spread of the new innovation, but it also allows for
      phases of coexistence. The existence of dual users largely modifies the transient
      dynamics creating new phases that promote the spread of a new innovation and
      extinction of a preexisting one. It enables the global spread of the new
      innovation even if the old one has the first-mover advantage.

PMID- 30275521
TI  - The majority is uncultured.

PMID- 30275522
TI  - Engineered mRNA-expressed antibodies prevent respiratory syncytial virus
      infection.
AB  - The lung is a critical prophylaxis target for clinically important infectious
      agents, including human respiratory syncytial virus (RSV) and influenza. Here, we
      develop a modular, synthetic mRNA-based approach to express neutralizing
      antibodies directly in the lung via aerosol, to prevent RSV infections. First, we
      express palivizumab, which reduces RSV F copies by 90.8%. Second, we express
      engineered, membrane-anchored palivizumab, which prevents detectable infection in
      transfected cells, reducing in vitro titer and in vivo RSV F copies by 99.7% and
      89.6%, respectively. Finally, we express an anchored or secreted high-affinity,
      anti-RSV F, camelid antibody (RSV aVHH and sVHH). We demonstrate that RSV aVHH,
      but not RSV sVHH, significantly inhibits RSV 7 days post transfection, and we
      show that RSV aVHH is present in the lung for at least 28 days. Overall, our data
      suggests that expressing membrane-anchored broadly neutralizing antibodies in the
      lungs could potentially be a promising pulmonary prophylaxis approach.

PMID- 30275524
TI  - Changes in body composition and metabolic disease risk.
AB  - As individuals gain weight, they increase the amount of fat that they accrue on
      their body. This causes adipocytes to enlarge and increases not only subcutaneous
      fat but also deposits fat in other vulnerable areas of the body. This ectopic fat
      is deposited in the intra-abdominal visceral fat depot, in muscle, in the liver
      and in the beta cells. Fat in these locations initiates a dysfunctional state in
      these insulin-sensitive tissues leading to insulin resistance, the appearance of
      the Metabolic Syndrome, and an increased risk of developing both type 2 diabetes
      and cardiovascular disease. A loss of weight and with it a loss of fat decreases
      this risk.

PMID- 30275523
TI  - Expanded A-DROP Score: A New Scoring System for the Prediction of Mortality in
      Hospitalized Patients with Community-acquired Pneumonia.
AB  - There are several established prognostic scoring systems for community-acquired
      pneumonia (CAP). The Pneumonia Severity Index (PSI) is a prediction rule
      consisting of 20 variables to identify low-risk patients with CAP. Although PSI
      had high discrimination ability, it is complex to calculate and difficult to use
      in busy hospital settings. The CURB-65 score is much simpler to use than is PSI,
      but it has lower sensitivity for predicting mortality compared with PSI. The A
      DROP score is a modified version of the CURB-65 score and provides similar
      predictive power to that of CURB-65. This study was performed to determine
      whether a simpler score (CURB-65, A-DROP), expanded with a small number of
      additional variables, can predict mortality more accurately than PSI. We
      conducted a retrospective observational study of 1,031 patients with CAP who were
      hospitalized at a tertiary teaching hospital. We used age, sex, comorbidities,
      vital signs, and laboratory findings as prognostic variables. We compared the
      PSI, CURB-65, and A-DROP scores using receiver operating characteristic curve
      analysis. The areas under the curves (AUCs) of PSI, CURB-65, and A-DROP were
      0.735, 0.701, and 0.730, respectively.Multivariable analysis identified
      malignancy [odds ratio (OR): 2.17, 95% confidence interval (CI): 1.13-4.17],
      respiration rate >= 24/min [OR: 2.18, 95% CI: 1.24-3.82], heart rate >= 100/min
      [OR: 2.92, 95% CI: 1.68-5.08], albumin <= 3.09 g/dL [OR: 3.85, 95% CI: 2.09
      7.07], lactate > 1.7 mmol/L [OR: 2.59, 95% CI: 1.53-4.38], and N-terminal
      prohormone brain natriuretic peptide > 500 pg/mL [OR: 2.23, 95% CI: 1.26-3.95] as
      prognostic factors. Using the prognostic variables identified in the
      multivariable analysis, we assembled a new scoring system, the expanded A-DROP
      score. The AUC of this score for the prediction of 28-day mortality was 0.834
      (95% CI: 0.794-0.874). Bootstrap validation yielded an estimated AUC of 0.833,
      indicating negligible overfitting of the model.The expanded A-DROP score is a
      relatively simple and effective scoring system, and its predictive value was
      superior to those of other scoring systems.

PMID- 30275525
TI  - The NF1 hotspot in acute myeloid leukemia: what's in a name?

PMID- 30275526
TI  - Cytogenetics and gene mutations influence survival in older patients with acute
      myeloid leukemia treated with azacitidine or conventional care.
AB  - Older patients with newly diagnosed acute myeloid leukemia (AML) in the phase 3
      AZA-AML-001 study were evaluated at entry for cytogenetic abnormalities, and a
      subgroup of patients was assessed for gene mutations. Patients received
      azacitidine 75 mg/m2/day x7 days (n = 240) or conventional care regimens (CCR; n
      = 245): intensive chemotherapy, low-dose cytarabine, or best supportive care
      only. Overall survival (OS) was assessed for patients with common (occurring in
      >=10% of patients) cytogenetic abnormalities and karyotypes, and for patients
      with recurring gene mutations. There was a significant OS improvement with
      azacitidine vs CCR for patients with European LeukemiaNet-defined Adverse
      karyotype (HR 0.71 [95%CI 0.51-0.99]; P = 0.046). Azacitidine-treated patients
      with -5/5q-, -7/7q-, or 17p abnormalities, or with monosomal or complex
      karyotypes, had a 31-46% reduced risk of death vs CCR. The most frequent gene
      mutations were DNMT3A (27%), TET2 (25%), IDH2 (23% [R140, 15%; R172, 8%]), and
      TP53 (21%). Compared with wild-type, OS was significantly reduced among CCR
      treated patients with TP53 or NRAS mutations and azacitidine-treated patients
      with FLT3 or TET2 mutations. Azacitidine may be a preferred treatment for older
      patients with AML with Adverse-risk cytogenetics, particularly those with
      chromosome 5, 7, and/or 17 abnormalities and complex or monosomal karyotypes. The
      influence of gene mutations in azacitidine-treated patients warrants further
      study.

PMID- 30275527
TI  - Mlh1 deficiency increases the risk of hematopoietic malignancy after simulated
      space radiation exposure.
AB  - Cancer-causing genome instability is a major concern during space travel due to
      exposure of astronauts to potent sources of high-linear energy transfer (LET)
      ionizing radiation. Hematopoietic stem cells (HSCs) are particularly susceptible
      to genotoxic stress, and accumulation of damage can lead to HSC dysfunction and
      oncogenesis. Our group recently demonstrated that aging human HSCs accumulate
      microsatellite instability coincident with loss of MLH1, a DNA Mismatch Repair
      (MMR) protein, which could reasonably predispose to radiation-induced HSC
      malignancies. Therefore, in an effort to reduce risk uncertainty for cancer
      development during deep space travel, we employed an Mlh1+/- mouse model to study
      the effects high-LET 56Fe ion space-like radiation. Irradiated Mlh1+/- mice
      showed a significantly higher incidence of lymphomagenesis with 56Fe ions
      compared to gamma-rays and unirradiated mice, and malignancy correlated with
      increased MSI in the tumors. In addition, whole-exome sequencing analysis
      revealed high SNVs and INDELs in lymphomas being driven by loss of Mlh1 and
      frequently mutated genes had a strong correlation with human leukemias.
      Therefore, the data suggest that age-related MMR deficiencies could lead to HSC
      malignancies after space radiation, and that countermeasure strategies will be
      required to adequately protect the astronaut population on the journey to Mars.

PMID- 30275529
TI  - CRISPR-Cas9-mediated base-editing screening in mice identifies DND1 amino acids
      that are critical for primordial germ cell development.
AB  - CRISPR-mediated base editing can introduce single-nucleotide changes in the DNA
      of living cells. One intriguing application of base editing is to screen pivotal
      amino acids for protein function in vivo; however, it has not been achieved.
      Here, we report an enhanced third-generation base-editing system with extra
      nuclear localization sequences that can efficiently introduce a homozygous base
      mutation in embryonic stem cells. Meanwhile, we establish a strategy to generate
      base-mutant mice by injection of haploid embryonic stem cells carrying a
      constitutively expressed enhanced third-generation base-editing system (4B2N1)
      and single guide RNA into oocytes. Moreover, transfection of 4B2N1 cells with a
      single guide RNA library targeting the Dnd1 gene allows one-step generation of
      mutant mice with a base mutation. This enables the identification of four
      missense mutations that completely deplete primordial germ cells through
      disruption of DND1 protein stability and protein-protein interaction. Thus, our
      strategy provides an effective tool for in vivo screening of amino acids that are
      crucial for protein function.

PMID- 30275528
TI  - Sequential high-dose cytarabine and mitoxantrone (S-HAM) versus standard double
      induction in acute myeloid leukemia-a phase 3 study.
AB  - Dose-dense induction with the S-HAM regimen was compared to standard double
      induction therapy in adult patients with newly diagnosed acute myeloid leukemia.
      Patients were centrally randomized (1:1) between S-HAM (2nd chemotherapy cycle
      starting on day 8 = "dose-dense") and double induction with TAD-HAM or HAM(-HAM)
      (2nd cycle starting on day 21 = "standard"). 387 evaluable patients were randomly
      assigned to S-HAM (N = 203) and to standard double induction (N = 184). The
      primary endpoint overall response rate (ORR) consisting of complete remission
      (CR) and incomplete remission (CRi) was not significantly different (P = 0.202)
      between S-HAM (77%) and double induction (72%). The median overall survival was
      35 months after S-HAM and 25 months after double induction (P = 0.323). Duration
      of critical leukopenia was significantly reduced after S-HAM (median 29 days)
      versus double induction (median 44 days)-P < 0.001. This translated into a
      significantly shortened duration of hospitalization after S-HAM (median 37 days)
      as compared to standard induction (median 49 days)-P < 0.001. In conclusion, dose
      dense induction therapy with the S-HAM regimen shows favorable trends but no
      significant differences in ORR and OS compared to standard double induction. S
      HAM significantly shortens critical leukopenia and the duration of
      hospitalization by 2 weeks.

PMID- 30275532
TI  - Damping of selectively bonded 3D woven lattice materials.
AB  - The objective of this paper is to unveil a novel damping mechanism exhibited by
      3D woven lattice materials (3DW), with emphasis on response to high-frequency
      excitations. Conventional bulk damping materials, such as rubber, exhibit
      relatively low stiffness, while stiff metals and ceramics typically have
      negligible damping. Here we demonstrate that high damping and structural
      stiffness can be simultaneously achieved in 3D woven lattice materials by brazing
      only select lattice joints, resulting in a load-bearing lattice frame intertwined
      with free, 'floating' lattice members to generate damping. The produced material
      samples are comparable to polymers in terms of damping coefficient, but are
      porous and have much higher maximum use temperature. We shed light on a novel
      damping mechanism enabled by an interplay between the forcing frequency imposed
      onto a load-bearing lattice frame and the motion of the embedded, free-moving
      lattice members. This novel class of damping metamaterials has potential use in a
      broad range of weight sensitive applications that require vibration attenuation
      at high frequencies.

PMID- 30275533
TI  - Inflammatory bowel disease: DCs sense LTB4 to drive TH1 and TH17 differentiation.

PMID- 30275531
TI  - Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million
      Veteran Program.
AB  - The Million Veteran Program (MVP) was established in 2011 as a national research
      initiative to determine how genetic variation influences the health of US
      military veterans. Here we genotyped 312,571 MVP participants using a custom
      biobank array and linked the genetic data to laboratory and clinical phenotypes
      extracted from electronic health records covering a median of 10.0 years of
      follow-up. Among 297,626 veterans with at least one blood lipid measurement,
      including 57,332 black and 24,743 Hispanic participants, we tested up to around
      32 million variants for association with lipid levels and identified 118 novel
      genome-wide significant loci after meta-analysis with data from the Global Lipids
      Genetics Consortium (total n > 600,000). Through a focus on mutations predicted
      to result in a loss of gene function and a phenome-wide association study, we
      propose novel indications for pharmaceutical inhibitors targeting PCSK9
      (abdominal aortic aneurysm), ANGPTL4 (type 2 diabetes) and PDE3B (triglycerides
      and coronary disease).

PMID- 30275534
TI  - Shining light on the significance of NK cell CD56 brightness.

PMID- 30275530
TI  - Sixteen diverse laboratory mouse reference genomes define strain-specific
      haplotypes and novel functional loci.
AB  - We report full-length draft de novo genome assemblies for 16 widely used inbred
      mouse strains and find extensive strain-specific haplotype variation. We identify
      and characterize 2,567 regions on the current mouse reference genome exhibiting
      the greatest sequence diversity. These regions are enriched for genes involved in
      pathogen defence and immunity and exhibit enrichment of transposable elements and
      signatures of recent retrotransposition events. Combinations of alleles and genes
      unique to an individual strain are commonly observed at these loci, reflecting
      distinct strain phenotypes. We used these genomes to improve the mouse reference
      genome, resulting in the completion of 10 new gene structures. Also, 62 new
      coding loci were added to the reference genome annotation. These genomes
      identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874
      amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions,
      suggesting a possible role for this gene in the regulation of brain development.

PMID- 30275536
TI  - IL-33 drives the antitumor effects of dendritic cells via the induction of Tc9
      cells.
AB  - Dendritic cell (DC) tumor vaccines exert their antitumor effects through the
      induction of effector T cells. We recently identified Tc9 cells as a new potent
      antitumor effector T cell subset. However, approaches to direct DCs to preferably
      prime antitumor Tc9 cells should be further exploited. Here, we demonstrate that
      the addition of interleukin (IL)-33 potently promotes the induction of Tc9 cells
      by DCs in vitro and in vivo. IL-33 treatment also drives the cytotoxic activities
      of DC-induced Tc9 cells. Notably, IL-33 treatment enhances cell survival and
      proliferation of DC-primed CD8+ T cells. More importantly, the addition of IL-33
      during in vitro priming of tumor-specific Tc9 cells by DCs increases the
      antitumor capability of Tc9 cells. Mechanistic studies demonstrated that IL-33
      treatment inhibits exhaustive CD8+ T cell differentiation by inhibiting PD-1 and
      2B4 expression and increasing IL-2 and CD127 (IL-7 receptor-alpha, IL-7Ralpha)
      expression in CD8+ T cells. Finally, the addition of IL-33 further promotes the
      therapeutic efficacy of DC-based tumor vaccines in the OT-I mouse model. Our
      study demonstrates the important role of IL-33 in DC-induced Tc9 cell
      differentiation and antitumor immunity and may have important clinical
      implications.

PMID- 30275535
TI  - E3 ligase FBXW7 aggravates TMPD-induced systemic lupus erythematosus by promoting
      cell apoptosis.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, and the
      pathogenesis of SLE has not been fully elucidated. The E3 ubiquitin ligase FBXW7
      has been well characterized in cancer as a tumor suppressor that can promote the
      ubiquitination and subsequent degradation of various oncoproteins; however, the
      potential role of FBXW7 in autoimmune diseases is unclear. In the present study,
      we identified that FBXW7 is a crucial exacerbating factor for SLE development and
      progression in a mouse model induced by 2, 6, 10, 14-tetramethylpentadecane
      (TMPD). Myeloid cell-specific FBXW7-deficient (Lysm+FBXW7f/f) C57BL/6 mice showed
      decreased immune complex accumulation, glomerulonephritis, glomerular mesangial
      cell proliferation, and base-membrane thickness in the kidney. Lysm+FBXW7f/f mice
      produced fewer anti-Sm/RNP and anti-ANA autoantibodies and showed a decreased MHC
      II expression in B cells. In Lysm+FBXW7f/f mice, we observed that cell apoptosis
      was reduced and that fewer CD11b+Ly6Chi inflammatory monocytes were recruited to
      the peritoneal cavity. Consistently, diffuse pulmonary hemorrhage (DPH) was also
      decreased in Lysm+FBXW7f/f mice. Mechanistically, we clarified that FBXW7
      promoted TMPD-induced cell apoptosis by catalyzing MCL1 degradation through K48
      linked ubiquitination. Our work revealed that FBXW7 expression in myeloid cells
      played a crucial role in TMPD-induced SLE progression in mice, which may provide
      novel ideas and theoretical support for understanding the pathogenesis of SLE.

PMID- 30275538
TI  - Targeting PVR (CD155) and its receptors in anti-tumor therapy.
AB  - Poliovirus receptor (PVR, CD155) has recently been gaining scientific interest as
      a therapeutic target in the field of tumor immunology due to its prominent
      endogenous and immune functions. In contrast to healthy tissues, PVR is expressed
      at high levels in several human malignancies and seems to have protumorigenic and
      therapeutically attractive properties that are currently being investigated in
      the field of recombinant oncolytic virotherapy. More intriguingly, PVR
      participates in a considerable number of immunoregulatory functions through its
      interactions with activating and inhibitory immune cell receptors. These
      functions are often modified in the tumor microenvironment, contributing to tumor
      immunosuppression. Indeed, increasing evidence supports the rationale for
      developing strategies targeting these interactions, either in terms of checkpoint
      therapy (i.e., targeting inhibitory receptors) or in adoptive cell therapy, which
      targets PVR as a tumor marker.

PMID- 30275537
TI  - NKR-P1B expression in gut-associated innate lymphoid cells is required for the
      control of gastrointestinal tract infections.
AB  - Helper-type innate lymphoid cells (ILC) play an important role in intestinal
      homeostasis. Members of the NKR-P1 gene family are expressed in various innate
      immune cells, including natural killer (NK) cells, and their cognate Clr ligand
      family members are expressed in various specialized tissues, including the
      intestinal epithelium, where they may play an important role in mucosal
      associated innate immune responses. In this study, we show that the inhibitory
      NKR-P1B receptor, but not the Ly49 receptor, is expressed in gut-resident NK
      cells, ILC, and a subset of gammadeltaT cells in a tissue-specific manner. ILC3
      cells constitute the predominant cell subset expressing NKR-P1B in the gut lamina
      propria. The known NKR-P1B ligand Clr-b is broadly expressed in gut-associated
      cells of hematopoietic origin. The genetic deletion of NKR-P1B results in a
      higher frequency and number of ILC3 and gammadeltaT cells in the gut lamina
      propria. However, the function of gut-resident ILC3, NK, and gammadeltaT cells in
      NKR-P1B-deficient mice is impaired during gastrointestinal tract infection by
      Citrobacter rodentium or Salmonella typhimurium, resulting in increased systemic
      bacterial dissemination in NKR-P1B-deficient mice. Our findings highlight the
      role of the NKR-P1B:Clr-b recognition system in the modulation of intestinal
      innate immune cell functions.

PMID- 30275539
TI  - Methyltransferase Dot1l preferentially promotes innate IL-6 and IFN-beta
      production by mediating H3K79me2/3 methylation in macrophages.
AB  - Epigenetic modification, including histone modification, precisely controls
      target gene expression. The posttranscriptional regulation of the innate
      signaling-triggered production of inflammatory cytokines and type I interferons
      has been fully elucidated, whereas the roles of histone modification alteration
      and epigenetic modifiers in regulating inflammatory responses need to be further
      explored. Di/tri-methylation modifications of histone 3 lysine 79 (H3K79me2/3)
      have been shown to be associated with gene transcriptional activation. Disruptor
      of telomeric silencing-1-like (Dot1l) is the only known exclusive H3K79
      methyltransferase and regulates the proliferation and differentiation of tumor
      cells. However, the roles of Dot1l and Dot1l-mediated H3K79 methylation in innate
      immunity and inflammatory responses remain unclear. Here, we found that
      H3K79me2/3 modification levels at the Il6 and Ifnb1 promoters, as well as
      H3K79me2 modification at the Tnfalpha promoter, were increased in macrophages
      activated by Toll-like receptor (TLR) ligands or virus infection. The innate
      signals upregulated Dot1l expression in macrophages and THP1 cells. Dot1l
      silencing or a Dot1l inhibitor preferentially suppressed the production of IL-6
      and interferon (IFN)-beta but not of TNF-alpha in macrophages and THP1 cells
      triggered by TLR ligands or virus infection. Dot1l was recruited to the proximal
      promoter of the Il6 and Ifnb1 but not Tnfalpha gene and then mediated H3K79me2/3
      modification at the Il6 and Ifnb1 promoters, consequently facilitating the
      transcription and expression of Il6 and Ifnb1. Thus, Dot1l-mediated selective
      H3K79me2/3 modifications at the Il6 and Ifnb1 promoters are required for the full
      activation of innate immune responses. This finding adds new insights into the
      epigenetic regulation of inflammatory responses and pathogenesis of autoimmune
      diseases.

PMID- 30275540
TI  - Coupled microbial bloom and oxygenation decline recorded by magnetofossils during
      the Palaeocene-Eocene Thermal Maximum.
AB  - Understanding marine environmental change and associated biological turnover
      across the Palaeocene-Eocene Thermal Maximum (PETM; ~56 Ma)-the most pronounced
      Cenozoic short-term global warming event-is important because of the potential
      role of the ocean in atmospheric CO2 drawdown, yet proxies for tracing marine
      productivity and oxygenation across the PETM are limited and results remain
      controversial. Here we show that a high-resolution record of South Atlantic Ocean
      bottom water oxygenation can be extracted from exceptionally preserved
      magnetofossils-the bioinorganic magnetite nanocrystals produced by magnetotactic
      bacteria (MTB) using a new multiscale environmental magnetic approach. Our
      results suggest that a transient MTB bloom occurred due to increased nutrient
      supply. Bottom water oxygenation decreased gradually from the onset to the peak
      PETM. These observations provide a record of microbial response to the PETM and
      establish the value of magnetofossils as palaeoenvironmental indicators.

PMID- 30275541
TI  - LISA improves statistical analysis for fMRI.
AB  - One of the principal goals in functional magnetic resonance imaging (fMRI) is the
      detection of local activation in the human brain. However, lack of statistical
      power and inflated false positive rates have recently been identified as major
      problems in this regard. Here, we propose a non-parametric and threshold-free
      framework called LISA to address this demand. It uses a non-linear filter for
      incorporating spatial context without sacrificing spatial precision. Multiple
      comparison correction is achieved by controlling the false discovery rate in the
      filtered maps. Compared to widely used other methods, it shows a boost in
      statistical power and allows to find small activation areas that have previously
      evaded detection. The spatial sensitivity of LISA makes it especially suitable
      for the analysis of high-resolution fMRI data acquired at ultrahigh field (>=7
      Tesla).

PMID- 30275542
TI  - Higher ambient synaptic glutamate at inhibitory versus excitatory neurons
      differentially impacts NMDA receptor activity.
AB  - Selective disruption of synaptic drive to inhibitory neurons could contribute to
      the pathophysiology of various brain disorders. We have previously identified a
      GluN2A-selective positive allosteric modulator, GNE-8324, that selectively
      enhances N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic responses in
      inhibitory but not excitatory neurons. Here, we demonstrate that differences in
      NMDAR subunit composition do not underlie this selective potentiation. Rather, a
      higher ambient glutamate level in the synaptic cleft of excitatory synapses on
      inhibitory neurons is a key factor. We show that increasing expression of
      glutamate transporter 1 (GLT-1) eliminates GNE-8324 potentiation in inhibitory
      neurons, while decreasing GLT-1 activity enables potentiation in excitatory
      neurons. Our results reveal an unsuspected difference between excitatory synapses
      onto different neuronal types, and a more prominent activation of synaptic NMDARs
      by ambient glutamate in inhibitory than excitatory neurons. This difference has
      implications for tonic NMDAR activity/signaling and the selective modulation of
      inhibitory neuron activity to treat brain disorders.

PMID- 30275543
TI  - A flow platform for degradation-free CuAAC bioconjugation.
AB  - The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a cornerstone
      method for the ligation of biomolecules. However, undesired Cu-mediated oxidation
      and Cu-contamination in bioconjugates limits biomedical utility. Here, we report
      a generic CuAAC flow platform for the rapid, robust, and broad-spectrum formation
      of discrete triazole bioconjugates. This process leverages an engineering problem
      to chemical advantage: solvent-mediated Cu pipe erosion generates ppm levels of
      Cu in situ under laminar flow conditions. This is sufficient to catalyze the
      CuAAC reaction of small molecule alkynes and azides, fluorophores, marketed drug
      molecules, peptides, DNA, and therapeutic oligonucleotides. This flow approach,
      not replicated in batch, operates at ambient temperature and pressure, requires
      short residence times, avoids oxidation of sensitive functional groups, and
      produces products with very low ppm Cu contamination.

PMID- 30275544
TI  - Transmission infrared spectroscopy for rapid quantification of fat, protein, and
      lactose concentrations in human milk.
AB  - OBJECTIVE: To develop partial least squares regression (PLSR) calibration models
      in combination with transmission infrared (TIR) spectroscopy for rapid and
      optimal quantification of human milk macronutrient concentrations. STUDY DESIGN:
      Human milk samples (n = 306) were characterized simultaneously by reference
      chemical analytical methods and TIR spectroscopy. Reference macronutrient
      concentrations were linked to pre-processed spectra and divided into two
      (training and test) sets. PLSR was used to develop trial calibration models using
      training set, and the test set was used to assess the accuracy of the trial
      analytical methods. RESULTS: For the methods selected as optimal, the concordance
      correlation coefficients between reference and TIR-based methods were 0.93 for
      fat, 0.96 for protein, and 0.52 for lactose. The Bland-Altman plots showed no
      evidence of systematic bias between TIR and reference methods. CONCLUSIONS: TIR
      spectroscopy provides the basis for accurate and rapid quantification of human
      milk fat and protein concentrations but is less accurate for measuring lactose
      concentration.

PMID- 30275545
TI  - Outcomes of early inhaled nitric oxide use in premature African American
      neonates.
AB  - OBJECTIVE: Meta-analysis of individual-patient clinical trial data suggests that
      inhaled nitric oxide (iNO) improves respiratory outcomes in premature African
      American neonates. We hypothesized that early iNO therapy would be associated
      with lower mortality and less chronic lung disease (CLD) in extremely premature
      African American neonates. STUDY DESIGN: We conducted a retrospective cohort
      study of propensity score- and race-matched neonates 22-29 weeks gestation who
      were mechanically ventilated for treatment of respiratory distress and associated
      pulmonary hypertension (RDS + PPHN). We evaluated the association of iNO within 7
      days of life with in-hospital mortality and CLD, using Cox proportional hazards
      regression and logistic regression, respectively. RESULT: Among 178 matched pairs
      of African American patients, iNO was not associated with lower mortality (HR =
      0.94, 95% CI 0.69-1.30) or less CLD (OR = 0.94, 95% CI 0.47-1.87). CONCLUSIONS:
      Early, off-label iNO use is not associated with improved outcomes in premature
      African American neonates with RDS + PPHN.

PMID- 30275546
TI  - Comprehensive analysis of the tumor immune micro-environment in non-small cell
      lung cancer for efficacy of checkpoint inhibitor.
AB  - Characterizing the molecular immune subtype and micro-environment of lung cancer
      is necessary to understand immunogenic interactions between infiltrating immune
      and stromal cells, and how tumor cells overcome immune checkpoint blockades. This
      study seeks to identify computational methodologies for subtyping gene expression
      based tumor-immune micro-environment interactions, which differentiate non-small
      cell lung cancer (NSCLC) into immune-defective and immune-competent subtypes.
      Here, 101 lung squamous cell carcinomas (LUSCs) and 87 lung adenocarcinomas
      (LUADs) tumor samples have been analyzed. Several micro-environmental factors
      differentially induce LUAD or LUSC immune subtypes, as well as immune checkpoint
      expression. In particular, tumor-associated macrophages (TAMs) are key immune
      cells play a vital role in inflammation and cancer micro-environments of LUSCs;
      whereas, regulatory B cells are immunosuppressive and tumorigenic in LUADs.
      Additionally, cytolytic activity upon CD8+ T cell activation is decreased by the
      abundance of B cells and macrophages in immune-competent subtypes. Therefore,
      identifying immune subtypes in lung cancer and their impact on tumor micro
      environment will lead to clinical tools for assessing LUADs and LUSCs in
      patients, as well as maximize the efficacy of immune checkpoint inhibitors.

PMID- 30275548
TI  - Neighbourhood deaths cause a switch in cancer subtype.

PMID- 30275547
TI  - The de novo design of a biocompatible and functional integral membrane protein
      using minimal sequence complexity.
AB  - The de novo design of integral membrane proteins remains a major challenge in
      protein chemistry. Here, we describe the bottom-up design of a genetically
      encoded synthetic membrane protein comprising only four amino acids (L, S, G and
      W) in the transmembrane domains. This artificial sequence, which we call REAMP
      for recombinantly expressed artificial membrane protein, is a single chain of 133
      residues arranged into four antiparallel membrane-spanning alpha-helices. REAMP
      was overexpressed in Escherichia coli and localized to the cytoplasmic membrane
      with the intended transmembrane topology. Recombinant REAMP could be extracted
      from the cell membrane in detergent micelles and was robust and stable in vitro,
      containing helical secondary structure consistent with the original design.
      Engineered mono- and bis-histidine residues in the membrane domain of REAMP were
      able to coordinate heme in vitro, in a manner reminiscent of natural b-type
      cytochromes. This binding shifted the electrochemical potential of the cofactor,
      producing a synthetic hemoprotein capable of nascent redox catalysis. These
      results show that a highly reduced set of amino acids is sufficient to mimic some
      key properties of natural proteins, and that cellular biosynthesis is a viable
      route for the production of minimal de novo membrane sequences.

PMID- 30275549
TI  - The electrifying energy of gut microbes.

PMID- 30275550
TI  - Put to sleep by immune cells.

PMID- 30275552
TI  - The hidden talent of a dangerous Icelandic volcano.

PMID- 30275551
TI  - Blood flow forces liver growth.

PMID- 30275553
TI  - Gene-snipping tool swats mosquitoes.

PMID- 30275554
TI  - Infants attuned to others' fear become altruistic toddlers.

PMID- 30275555
TI  - An aggressive cancer's road to conquest.

PMID- 30275556
TI  - Jupiter takes an annual pummelling from the Solar System.

PMID- 30275558
TI  - Record-breaking battery saves sunshine for a rainy day.

PMID- 30275559
TI  - On the record.

PMID- 30275560
TI  - Farmers transformed how we investigate climate.

PMID- 30275561
TI  - Guidance cues: linking drug use in adolescence with psychiatric disorders.

PMID- 30275562
TI  - XIAP facilitates breast and colon carcinoma growth via promotion of p62 depletion
      through ubiquitination-dependent proteasomal degradation.
AB  - X-linked inhibitor of apoptosis protein (XIAP) possesses a critical role in
      promotion of cell survival and maintenance of cellular homeostasis. In cancer,
      elevated XIAP expression has been associated with malignancy, poor prognosis, and
      treatment resistance. However, the underlying mechanisms of these effects remain
      unclear. XIAP has previously been proposed to promote tumor growth through
      suppression of autophagy. In this study, we examined the expression of XIAP and
      p62, two critical mediators of autophagy, in breast and colon cancer. We observed
      a negative correlation between XIAP and p62 expression in normal and cancer
      tissues of breast and colon, and that the ratio of XIAP and p62 expression
      determines the cancer phenotype. In vitro, we observed that XIAP interacted with
      p62 and also that XIAP depletion resulted in increased expression of p62. XIAP
      functioned as an ubiquitination E3 ligase towards p62 and suppressed p62
      expression through ubiquitin-proteasomal degradation. Furthermore, XIAP enhanced
      cancer cell proliferation, viability, and colony formation in vitro via
      suppression of p62. In addition, we demonstrated that XIAP-enhanced tumor growth
      is dependent on depletion of p62 in vivo. Herein, we have therefore delineated a
      novel mechanism by which XIAP contributes to development and progression of
      breast and colon carcinoma.

PMID- 30275563
TI  - Julia Randall Weertman (1926-2018).

PMID- 30275564
TI  - Topological quantum properties of chiral crystals.
AB  - Chiral crystals are materials with a lattice structure that has a well-defined
      handedness due to the lack of inversion, mirror or other roto-inversion
      symmetries. Although it has been shown that the presence of crystalline
      symmetries can protect topological band crossings, the topological electronic
      properties of chiral crystals remain largely uncharacterized. Here we show that
      Kramers-Weyl fermions are a universal topological electronic property of all non
      magnetic chiral crystals with spin-orbit coupling and are guaranteed by
      structural chirality, lattice translation and time-reversal symmetry. Unlike
      conventional Weyl fermions, they appear at time-reversal-invariant momenta. We
      identify representative chiral materials in 33 of the 65 chiral space groups in
      which Kramers-Weyl fermions are relevant to the low-energy physics. We determine
      that all point-like nodal degeneracies in non-magnetic chiral crystals with
      relevant spin-orbit coupling carry non-trivial Chern numbers. Kramers-Weyl
      materials can exhibit a monopole-like electron spin texture and topologically non
      trivial bulk Fermi surfaces over an unusually large energy window.

PMID- 30275565
TI  - Oxidation states and ionicity.
AB  - The concepts of oxidation state and atomic charge are entangled in modern
      materials science. We distinguish between these quantities and consider their
      fundamental limitations and utility for understanding material properties. We
      discuss the nature of bonding between atoms and the techniques that have been
      developed for partitioning electron density. While formal oxidation states help
      us count electrons (in ions, bonds, lone pairs), variously defined atomic charges
      are usefully employed in the description of physical processes including
      dielectric response and electronic spectroscopies. Such partial charges are
      introduced as quantitative measures in simple mechanistic models of a more
      complex reality, and therefore may not be comparable or transferable. In
      contrast, oxidation states are defined to be universal, with deviations
      constituting exciting challenges as evidenced in mixed-valence compounds,
      electrides and highly correlated systems. This Perspective covers how these
      concepts have evolved in recent years, our current understanding and their
      significance.

PMID- 30275567
TI  - The influence of ethnicity and geography on human gut microbiome composition.

PMID- 30275566
TI  - Renal compartment-specific genetic variation analyses identify new pathways in
      chronic kidney disease.
AB  - Chronic kidney disease (CKD), a condition in which the kidneys are unable to
      clear waste products, affects 700 million people globally. Genome-wide
      association studies (GWASs) have identified sequence variants for CKD; however,
      the biological basis of these GWAS results remains poorly understood. To address
      this issue, we created an expression quantitative trait loci (eQTL) atlas for the
      glomerular and tubular compartments of the human kidney. Through integrating the
      CKD GWAS with eQTL, single-cell RNA sequencing and regulatory region maps, we
      identified novel genes for CKD. Putative causal genes were enriched for proximal
      tubule expression and endolysosomal function, where DAB2, an adaptor protein in
      the TGF-beta pathway, formed a central node. Functional experiments confirmed
      that reducing Dab2 expression in renal tubules protected mice from CKD. In
      conclusion, compartment-specific eQTL analysis is an important avenue for the
      identification of novel genes and cellular pathways involved in CKD development
      and thus potential new opportunities for its treatment.

PMID- 30275568
TI  - Induction of resistance to chimeric antigen receptor T cell therapy by
      transduction of a single leukemic B cell.
AB  - We report a patient relapsing 9 months after CD19-targeted CAR T cell (CTL019)
      infusion with CD19- leukemia that aberrantly expressed the anti-CD19 CAR. The CAR
      gene was unintentionally introduced into a single leukemic B cell during T cell
      manufacturing, and its product bound in cis to the CD19 epitope on the surface of
      leukemic cells, masking it from recognition by and conferring resistance to
      CTL019.

PMID- 30275569
TI  - Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic
      leukemia.
AB  - We identified genetic mutations in CD19 and loss of heterozygosity at the time of
      CD19- relapse to chimeric antigen receptor (CAR) therapy. The mutations are
      present in the vast majority of resistant tumor cells and are predicted to lead
      to a truncated protein with a nonfunctional or absent transmembrane domain and
      consequently to a loss of surface antigen. This irreversible loss of CD19
      advocates for an alternative targeting or combination CAR approach.

PMID- 30275571
TI  - A detector for the sources.

PMID- 30275570
TI  - Dynamics of genetically engineered hematopoietic stem and progenitor cells after
      autologous transplantation in humans.
AB  - Hematopoietic stem and progenitor cells (HSPC) are endowed with the role of
      generating and maintaining lifelong the extremely diverse pool of blood cells1.
      Clinically, transplantation of human HSPC from an allogeneic healthy donor or
      infusion of autologous gene-corrected HSPC can effectively replenish defective
      blood cell production caused by congenital or acquired disorders2-9. However, due
      to methodological and ethical constraints that have limited the study of human
      HSPC primarily to in vitro assays10 or xenotransplantation models11,12, the in
      vivo activity of HSPC has to date remained relatively unexplored in humans13-16.
      Here we report a comprehensive study of the frequencies, dynamics and output of
      seven HSPC subtypes in humans that was performed by tracking 148,093 individual
      clones in six patients treated with lentiviral gene therapy using autologous HSPC
      transplantation and followed for up to 5 years. We discovered that primitive
      multipotent progenitor and hematopoietic stem cell (HSC) populations have
      distinct roles during the initial reconstitution after transplant, compared with
      subsequent steady-state phases. Furthermore, we showed that a fraction of in
      vitro-activated HSC are resilient and undergo a defined delayed activation period
      upon transplant. Finally, our data support the concept that early lymphoid-biased
      progenitors might be capable of long-term survival, such that they can be
      maintained independently of their continuous production from HSC. Overall, this
      study provides comprehensive data on HSPC dynamics after autologous
      transplantation and gene therapy in humans.

PMID- 30275572
TI  - Single-particle analysis for fluorescence nanoscopy.

PMID- 30275575
TI  - Raising the game in image classification.

PMID- 30275573
TI  - Qiita: rapid, web-enabled microbiome meta-analysis.
AB  - Multi-omic insights into microbiome function and composition typically advance
      one study at a time. However, in order for relationships across studies to be
      fully understood, data must be aggregated into meta-analyses. This makes it
      possible to generate new hypotheses by finding features that are reproducible
      across biospecimens and data layers. Qiita dramatically accelerates such
      integration tasks in a web-based microbiome-comparison platform, which we
      demonstrate with Human Microbiome Project and Integrative Human Microbiome
      Project (iHMP) data.

PMID- 30275574
TI  - Multicolor single-particle reconstruction of protein complexes.
AB  - Single-particle reconstruction (SPR) from electron microscopy (EM) images is
      widely used in structural biology, but it lacks direct information on protein
      identity. To address this limitation, we developed a computational and analytical
      framework that reconstructs and coaligns multiple proteins from 2D super
      resolution fluorescence images. To demonstrate our method, we generated
      multicolor 3D reconstructions of several proteins within the human centriole,
      which revealed their relative locations, dimensions and orientations.

PMID- 30275576
TI  - Better base editors.

PMID- 30275577
TI  - Modeling temperature during optogenetic illumination.

PMID- 30275578
TI  - Lighting up proteins.

PMID- 30275579
TI  - Evolving proteins with improved solubility.

PMID- 30275580
TI  - Proximity labeling with TurboID.

PMID- 30275581
TI  - Gentler super-resolution microscopy.

PMID- 30275582
TI  - Engineering wild bacteria.

PMID- 30275583
TI  - Large-sized bilayer nanodiscs.

PMID- 30275585
TI  - Phototoxicity revisited.

PMID- 30275584
TI  - Base editing a CRISPR way.

PMID- 30275586
TI  - Deep learning reaches the motor system.

PMID- 30275588
TI  - Coloring electron microscopy connectomes.

PMID- 30275587
TI  - All-optical synaptic electrophysiology probes mechanism of ketamine-induced
      disinhibition.
AB  - Optical assays of synaptic strength could facilitate studies of neuronal
      transmission and its dysregulation in disease. Here we introduce a genetic
      toolbox for all-optical interrogation of synaptic electrophysiology
      (synOptopatch) via mutually exclusive expression of a channelrhodopsin actuator
      and an archaerhodopsin-derived voltage indicator. Optically induced activity in
      the channelrhodopsin-expressing neurons generated excitatory and inhibitory
      postsynaptic potentials that we optically resolved in reporter-expressing
      neurons. We further developed a yellow spine-targeted Ca2+ indicator to localize
      optogenetically triggered synaptic inputs. We demonstrated synOptopatch
      recordings in cultured rodent neurons and in acute rodent brain slice. In
      synOptopatch measurements of primary rodent cultures, acute ketamine
      administration suppressed disynaptic inhibitory feedbacks, mimicking the effect
      of this drug on network function in both rodents and humans. We localized this
      action of ketamine to excitatory synapses onto interneurons. These results
      establish an in vitro all-optical model of disynaptic disinhibition, a synaptic
      defect hypothesized in schizophrenia-associated psychosis.

PMID- 30275589
TI  - A model for tumor-immune interaction.

PMID- 30275591
TI  - A tissue-to-organelle view of cellular proteins.

PMID- 30275590
TI  - Bridget Carragher.

PMID- 30275592
TI  - Assessing photodamage in live-cell STED microscopy.

PMID- 30275594
TI  - Mutation frequency is not increased in CRISPR-Cas9-edited mice.

PMID- 30275593
TI  - Fast and accurate data collection for macromolecular crystallography using the
      JUNGFRAU detector.
AB  - The accuracy of X-ray diffraction data is directly related to how the X-ray
      detector records photons. Here we describe the application of a direct-detection
      charge-integrating pixel-array detector (JUNGFRAU) in macromolecular
      crystallography (MX). JUNGFRAU features a uniform response on the subpixel level,
      linear behavior toward high photon rates, and low-noise performance across the
      whole dynamic range. We demonstrate that these features allow accurate MX data to
      be recorded at unprecedented speed. We also demonstrate improvements over
      previous-generation detectors in terms of data quality, using native single
      wavelength anomalous diffraction (SAD) phasing, for thaumatin, lysozyme, and
      aminopeptidase N. Our results suggest that the JUNGFRAU detector will
      substantially improve the performance of synchrotron MX beamlines and equip them
      for future synchrotron light sources.

PMID- 30275595
TI  - Does the number of chromosomes matter?

PMID- 30275596
TI  - CT-guided biopsy of the mediastinal masses. Can anatomical relationships predict
      complications?
AB  - AIM: To retrospectively evaluate the technical features, feasibility, efficacy,
      accuracy and appropriate complications of CT-guided biopsies of mediastinal
      masses and correlate them with anatomical relationships in the mediastinum.
      METHODS: Over the course of ten years, 81 percutaneous biopsy procedures in 78
      patients for tumors sizes 27 - 189 mm in diameter (median length 57.5 mm) were
      performed using only local anesthesia. These interventions were done under the
      guidance of computed tomography. The patients were men in 30 cases and women in
      48 cases, aged 19 to 90 years. RESULTS: In 78 cases (96.3%) results were either
      true positive or true negative; in only 3 cases (3.7%, 3 biopsies of 2 tumors in
      2 patients) were histological findings false negative. In 2.3% of the patients,
      complications were revealed in the anterior part of the mediastinum, 43.7%
      occurred in the middle region, and 14.3% in the posterior region of the
      mediastinum. Statistical data analysis verified there was a 3.74 times chance of
      an increase in complications in the middle mediastinal section in correlation
      with other anatomical localizations. In only one case was therapeutic
      intervention for complication necessary. For all other cases, a conservative
      approach was suitable. CONCLUSION: Percutaneous CT guided biopsies of the
      mediastinal tumors has a high accuracy rate in establishing the correct
      diagnosis. Masses in the middle mediastinum are associated with statistically
      higher incidences of postprocedural complications, which are not serious.

PMID- 30275597
TI  - Genetic architecture of recent-onset dilated cardiomyopathy in Moravian region
      assessed by whole-exome sequencing and its clinical correlates.
AB  - AIMS: Recent-onset dilated cardiomyopathy (RODCM) is a disease of heterogeneous
      aetiology and clinical outcome. In this pilot study, we aimed to assess its
      genetic architecture and correlate genotype with left ventricular reverse
      remodelling (LVRR). PATIENTS AND METHODS: In this multi-centre prospective
      observational study, we enrolled 83 Moravian patients with RODCM and a history of
      symptoms of less than 6 months, for whole-exome sequencing (WES). All patients
      underwent 12-month clinical and echocardiographic follow-up. LVRR was defined as
      an absolute increase in left ventricular ejection fraction > 10% accompanied by a
      relative decrease of left ventricular end-diastolic diameter > 10% at 12 months.
      RESULTS: WES identified at least one disease-related variant in 45 patients
      (54%). LVRR occurred in 28 patients (34%), most often in carriers of isolated
      titin truncated variants, followed by individuals with a negative, or
      inconclusive WES and carriers of other disease-related variants (56% vs. 42% vs.
      19%, P=0.041). CONCLUSION: A substantial proportion of RODCM cases have a
      monogenic or oligogenic genetic background. Carriers of non-titin disease-related
      variants are less likely to reach LVRR at 12- months than other individuals.
      Genetic testing could contribute to better prognosis prediction and
      individualized treatment of RODCM.

PMID- 30275599
TI  - On Being a Catholic Palliative Medicine Physician.

PMID- 30275598
TI  - Near-Infrared Fluorescent Probe for Sensitive Detection of Pb(II) Ions in Living
      Cells.
AB  - A new near-infrared fluorescent probe (NIR-PbP) for sensitive detection of Pb(II)
      ions in solution and living cells has been rationally designed and synthesized.
      The NIR-PbP is inherently non-fluorescent and gains fluorescence in the presence
      Pb(II) ions. The ion detection is based on Pb(II)-induced unmasking the
      fluorophore through the opening of the spyrocycle, with more than 500-fold
      fluorescence for sub-micromolar Pb(II) concentration. The NIR-PbP has high
      sensitivity, good photo-stability, low detection limit, and reversible response
      to Pb(II) ions.

PMID- 30275600
TI  - Practicing Medicine in Light of the Gospel.

PMID- 30275601
TI  - Benediction of Vanderbilt Christian Medical Student Graduates.

PMID- 30275602
TI  - "Mirror of Patients": A Reflection on the Honor of Serving as a Male Obstetrician
      gynecologist.
AB  - Physicians' work challenges them to learn and grow from their experiences with
      patients. Male obstetrician-gynecologists are uniquely blessed and challenged by
      their experiences in women's health care. The following is a reflection by one
      male obstetrician-gynecologist who considers the role of Saint Joseph in the holy
      family in contemplating his own role in providing women's health care. Summary:
      One hundred twenty-five men who underwent therapy trying to change sexual
      orientation from homosexual to heterosexual were asked about negative and
      positive experiences. About two-thirds recorded changes of varying extent. There
      was also much decrease in suicidality, depression, and substance abuse, and
      increases in social functioning and self-esteem. Almost all harmful effects were
      none to slight and comparable to therapies for other unwelcome conditions.

PMID- 30275604
TI  - An Operating Room Experience Necessitating Prayer: Through a Medical Student's
      Eyes.

PMID- 30275603
TI  - The Embrace of the Proabortion Turnaway Study: Wishful Thinking? or Willful
      Deceptions?
AB  - The abortion advocacy group Advancing New Standards in Reproductive Health
      (ANSIRH) has published over twenty papers based on a case series of women taking
      part in their Turnaway Study. Following the lead of ANSIRH news releases, major
      media outlets have described these results as proof that (a) most women who have
      abortions are glad they did, (b) there is no evidence of negative mental health
      effects following abortion, and (c) the only women really suffering are those who
      are being denied late-term abortions due to legal restrictions based on
      gestational age. Buried in ANSIRH's papers are the facts that over 68 percent of
      the women they sought to interview refused, their own evidence confirms that the
      remnant who did participate were atypical, there are no known benefits from
      abortion, their methods are misleadingly described, and their results are
      selectively reported. Summary: Widely publicized claims regarding the benefits of
      abortion for women have been discredited. The Turnaway Study, conducted by
      abortion advocates at thirty abortion clinics, reportedly proves that 95 percent
      of women have no regrets about their abortions and that abortion causes no mental
      health problems. But a new expose reveals that the authors have misled the
      public, using an unrepresentative, highly biased sample and misleading questions.
      In fact, over two-thirds of the women approached at the abortion clinics refused
      to be interviewed, and half of those who agreed dropped out. Refusers and
      dropouts are known to have more postabortion problems.

PMID- 30275605
TI  - Engage or Run: Reflections on My Intern Year.

PMID- 30275606
TI  - A Voice from the Past: Fifty Years Ago in The Linacre Quarterly.

PMID- 30275607
TI  - The Physician and the Sexual Revolution.

PMID- 30275609
TI  - Treatment of an Ectopic Pregnancy: An Ethical Reanalysis.
AB  - There is considerable lack of clarity on the medical facts surrounding management
      of ectopic pregnancy. In particular, it is not widely appreciated that by the
      time an ectopic pregnancy is diagnosed, in most cases, there is no viable fetus
      (i.e., the fetus has already died). Moreover, there is very little ethical
      guidance from the medical profession regarding the emotionally difficult decision
      to terminate a wanted pregnancy when the life of the mother is at risk. The best
      articulated positions on this topic come from religious groups, based on the
      principle of double effect. Yet the application of this reasoning to termination
      of an ectopic pregnancy is inconsistent with the medical facts in many cases. To
      resolve these inconsistencies, while still providing a robust ethical context for
      resolving such difficult situations, we propose clear guidelines for determining
      when a viable fetus is present in ectopic pregnancy and clarify the moral object
      in ectopic pregnancy management. Summary: This paper explores the ethical
      framework for clinical decision making in the case of ectopic pregnancies.
      Focusing on the disordered union of mother and unborn child clarifies the object
      and purpose of the actions used to separate the mother and fetus in order to save
      the life of both, or at least one. Since over 90% of tubal ectopic pregnancies
      present as embryos who have already died, these cases present no ethical dilemma.
      This paper proposes a modification of currently used criteria for determining the
      viability of ectopic pregnancies and calls for further research.

PMID- 30275608
TI  - Reducing the Risk of Gynecologic Cancer in Hereditary Breast Ovarian Cancer
      Syndrome Mutation Carriers: Moral Dilemmas and the Principle of Double Effect.
AB  - Hereditary breast ovarian cancer (HBOC) syndrome is an autosomal dominant disease
      linked to mutations in the BRCA1 and BRCA2 genes in 90 percent of affected
      families. Female mutation carriers are highly susceptible to aggressive, often
      disseminated, usually fatal pelvic-abdominal carcinomatosis. This cancer risk can
      be markedly reduced by surgical removal of the internal gynecologic organs before
      the end of the fourth decade of life and by using estrogen-progestin formulations
      marketed for many years as combined oral contraceptives (COCs). Both risk
      reducing methods are associated with unfavorable effects. Relying on the
      principle of double effect, this essay argues for the ethical justification of
      prophylactic surgery and the use of COC to reduce the risk of gynecologic cancer
      in HBOC syndrome mutation carriers. Summary: Hereditary breast ovarian cancer
      syndrome is an autosomal dominant disease linked to mutations in the BRCA1 and
      BRCA2 genes in most affected families. Female mutation carriers are highly
      susceptible to aggressive, often disseminated, usually fatal pelvic-abdominal
      carcinomatosis. This cancer risk can be markedly reduced by surgical removal of
      the internal gynecologic organs before the end of the fourth decade of life and
      by using estrogen-progestin formulations marketed for many years as combined oral
      contraceptives. Both risk-reducing methods are associated with unfavorable
      effects. Relying on the principle of double effect, this essay argues for the
      ethical justification for those unfavorable effects.

PMID- 30275610
TI  - The Ethics of Interstitial and Cesarean Scar Ectopic Pregnancies: Four Case
      Studies and a Review of the Literature.
AB  - Catholic bioethicists have extensively addressed extrauterine tubal pregnancies,
      which represent the great majority of ectopic pregnancies. However, additional
      management options have been developed for the other 7-10 percent of ectopic
      pregnancies. Using two cases of interstitial pregnancy and two cases of cesarean
      scar pregnancy (CSP) seen at a Catholic tertiary care center, this article
      discusses options including expectant management, systemic methotrexate,
      intragestational methotrexate, intragestational potassium chloride, uterine
      artery embolization, dilation and curettage (D&C), vasopressin use, cornuostomy,
      cornual wedge resection, CSP evacuation, CSP scar excision, CSP salvage, and
      hysterectomy. Cornual wedge resection, vasopressin use, and CSP scar excision are
      morally acceptable; less clearly licit are aspiration of gestational sac
      contents, cornuostomy, gestational excision for CSPs, and methotrexate. Certainly
      illicit are any techniques leading to direct abortion such as D&Cs on live
      embryos or fetuses, double-balloon catheter placement, and use of potassium
      chloride. Summary: An ectopic pregnancy is any pregnancy outside the uterus.
      These are dangerous because the pregnancy can burst out of its abnormal location
      and cause life-threatening internal bleeding. Most are in the part of the
      fallopian tube outside the uterus, but there are other types, including
      interstitial pregnancies (located in the part of the tube tunneling through the
      uterine wall) and cesarean scar pregnancies (buried in the uterine scar where the
      cut for a C-section was made). This article lists the ways that physicians
      prevent women from dying from interstitial and cesarean scar pregnancies and
      proposes which treatments are morally acceptable.

PMID- 30275611
TI  - Current Medical Research: Summer/Fall 2017.
AB  - This issue of Current Medical Research (CMR) includes studies that provide
      evidence that use of natural family planning (NFP) can be helpful for subfertile
      couples wishing to achieve a pregnancy, the effectiveness of a method of NFP
      during breastfeeding, and the effects of using NFP on marital relationships. This
      review also includes evidence on predicting the sex of a baby by timing
      intercourse, evidence that brain injuries can be reflected in changes in the
      menstrual cycle, and that women prefer methods of family planning that have no
      side effects. The issue ends with an in-depth review of new technologies that aid
      in the use of NFP. Topics covered include subfertile couples, breastfeeding,
      marriage, predicting the sex of a baby, brain injuries, and new technologies.

PMID- 30275612
TI  - dM-Dim for Carboxylic Acid Protection.
AB  - The 1,3-dithian-2-yl-methyl (Dim) and its analogous groups including dimethyl-Dim
      (dM-Dim) can provide a new dimension of orthogonality for carboxylic acid
      protection. They can be deprotected under nearly neutral oxidative conditions. In
      this paper, the protection of carboxylic acid with dM-Dim, deprotection of dM-Dim
      ester with sodium periodate, stability of dM-Dim protected carboxylic acid under
      acidic and basic conditions, and selective deprotection of dM-Dim protected
      carboxylic acids in the presence of tertiary butyl and methyl esters are
      presented.

PMID- 30275613
TI  - Specific Learning Disabilities: Issues that Remain Unanswered.

PMID- 30275614
TI  - Perception of Families of Children with Specific Learning Disorder: An
      Exploratory Study.
AB  - Background: Parents have a tremendous influence on their children's academic and
      social success. Unfortunately, a majority of them do not have a concrete idea on
      how to assist their children, impacting negatively on both the parents and the
      child. Currently, there is sparse research on parents' experiences in dealing
      with children with specific learning disorders (SLD). The current study was
      planned to explore the perception of families of children with SLD. Materials and
      Methods: Five focus group discussions (FGDs) including 30 parents of children
      with SLD aged between 8 and 14 years were carried out. Each group composed of
      five - seven participants. A format to guide FGDs was made to bring uniformity
      across groups. The transcripts were analyzed using the content analysis method to
      extract key conceptual themes. Results: The parents showed lack of conceptual
      knowledge with regard to the SLD symptomatology as well as proper guidelines to
      deal with their child's problem. They displayed negative attitudes and reactions
      toward their child's diagnosis of SLD, such as rejection, denial, over
      protection, and loss of hope. Their caregiving was also perceived to place
      physical, personal, social, financial, and emotional burden by the majority of
      parents. Conclusion: The study highlights the experiences of parents dealing with
      SLD in terms of their inadequate knowledge, adaptational difficulties, and
      burden. The findings also reiterate the need to focus on family perspective and
      experiences when working with a learning-disabled child. Various supportive
      strategies are required to empower families, which would help alleviate their
      burden. Moreover, parents' training to strengthen child's learning skills is also
      warranted.

PMID- 30275615
TI  - Children's Reactions to Flood Disaster in Kashmir.
AB  - Background: The flood disaster of 9th-10th September 2014 wreaked havoc in the
      Jammu and Kashmir region of India. Incessant rains and deluge claimed 283 lives
      and damaged 2.53 lakh houses. This article presents the findings of the
      psychosocial care team from the National Institute of Mental Health and Neuro
      Sciences, Bengaluru, India, during the early phase of disaster. Materials and
      Methods: The team assessed posttraumatic stress symptoms of 64 child survivors
      from six villages of two districts struck by floods using Children's Revised
      Impact of Event Scale (CRIES)-8 and qualitative narrations. Results: Children
      showed high levels of intrusion and avoidance in the aftermath of floods. Both
      boys and girls showed moderate to severe level of psychological impact on the
      domains of CRIES-8. The narrations by the children centred on the theme of
      "water" and "enjoyment in seeing lots of water;" followed by "fearing of the
      parent's life," later on "fear of their own life," and subsequently to avoidance
      to go near the river and nightmares like "floating in the water." Conclusion:
      Disasters immensely impact children because of their particular stage of
      psychological and social development. This highlights the need for psychosocial
      interventions to minimize the impact of disasters on children at the earliest
      using simple psychosocial care techniques by employing available community-based
      manpower.

PMID- 30275616
TI  - Adaptation of Subtests of Kaufman Assessment Battery for Children, Second Edition
      for Gujarati Pre-school Children.
AB  - Context: Cognition testing is frequently used in children to assess their
      intelligence for various needs. Abundant tests to assess cognition are available
      in the western world. The paucity of such tests for use in Gujarati population
      necessitates their adaptation for Gujarati culture. Aims: To adapt three subtests
      (Number Recall, Word Order, and Triangles) of Kaufman Assessment Battery for
      Children, Second Edition for Gujarati-speaking preschool age children using
      priori (judgemental) procedures of test adaptation process. Settings and Design:
      This was a prospective study of test adaptation process carried out in three
      kindergarten schools of Gujarat. Subjects and Methods: Three subtests were
      translated and adapted into Gujarati. A pilot study evaluating the applicability
      and appropriateness of the adapted version of the three tests was done, and the
      results of these raw scores were compared with English tests' scores. Of 68
      children (age 3-6 years) who completed the pilot study, 15 boys and 15 girls 4-6
      years of age were randomly selected to perform English tests for agreement
      between English and the adapted versions. Statistical Analysis Used: Agreement
      between the adapted and English versions of the tests was measured. Results:
      During adaptation, modifications were required only in the items of the Word
      order subtest. All children were able to understand and perform the test.
      Triangles did not require adaptation or modifications in test items. The
      agreement between raw scores of the two versions was good for both "Number
      Recall" (mean difference = 0.8, 95% confidence limits: -2.6, 4.1) and "Word
      Order" (mean difference = 0.6, 95% confidence limits: -3.2, 4.4). Conclusion:
      Adaptation of three subtests of KABC-II using a priori, that is, judgemental,
      procedure was suitable for Gujarati-speaking preschool children.

PMID- 30275617
TI  - Leisure Time Physical Activity and Risk of Developing Depression among the Youth
      of Kangra District, Himachal Pradesh, India.
AB  - Background: Physical inactivity during adolescence and youth has been considered
      as potential risk factor for future mental health problems. The present study was
      conducted with the aim to examine whether an association exists between leisure
      time physical activity (PA) and depression among the youth of Kangra district,
      studying in professional or degree colleges. Methodology: A cross-sectional study
      was conducted among the students of Medical College (MC), Central University (CU)
      and Industrial Training Institute (ITI) of Kangra district. 370 adolescents and
      youth of age <25 years, who consented to participate, were recruited. The sample
      size was divided into three parts among all the three institutes. Only one
      question regarding leisure time PA (LTPA) was asked, as to how many hours spent
      in the last week; and Center for Epidemiologic Studies Depression Scale for
      Children (CES-DC) was used. Results: There were 124 participants from ITI, 126
      from CU and 120 from MC. The mean score of CES-DC was highest among CU students
      22.7 (+/-11.0) and lowest among MC students; 13.6 (+/-9.2). Low LTPA (<4 h) was
      significantly associated with higher depressive symptoms among all students (odds
      ratio [95% confidence interval]; 3.34 [1.41-7.92]). Conclusion: LTPA was
      associated with lower rates of depression.

PMID- 30275618
TI  - What Adolescent Girls Know about Mental Health: Findings from a Mental Health
      Literacy Survey from an Urban Slum Setting in India.
AB  - Background: Youth in vulnerable situations are known to have high rates of mental
      disorders but low help-seeking. Help-seeking is known to be influenced by mental
      health literacy (MHL), a key concept that is important for the recognition of
      mental disorders and planning intervention. Aims: To explore MHL and help-seeking
      patterns in a group of young women in an urban slum setting in India. Materials
      and Methods: A total of 337 young women between 16 and 19 years of age belonging
      to urban slum settings formed the study sample. Two vignettes on depression and
      self-harm were used to assess: (a) recognition of the disorder, (b) help-seeking,
      and (c) knowledge of treatments available. Results: Only 8% of women were able to
      label the condition as depression in the first vignette. Though suicidality was
      identified correctly by the majority of participants 73 (63%), they did not think
      it needed urgent intervention. Only a few considered mental health professionals
      as possible sources of help (19.3% for depression and 2.4% for self-harm).
      Majority of the young women felt friends and parents were sources of help, and
      that stigma and lack of awareness were the reasons for not considering
      professional help. Conclusion: MHL regarding depression and suicidality is low
      among young women from low-income areas. It is a critical and urgent need to
      encourage early and appropriate help-seeking for mental health problems in this
      vulnerable population.

PMID- 30275619
TI  - Prevalence and Pattern of Phantom Ringing and Phantom Vibration among Medical
      Interns and their Relationship with Smartphone Use and Perceived Stress.
AB  - Background: Phantom sensations like phantom vibration (PV) and phantom ringing
      (PR)- the sensations of vibration and ringing of the phone when they are not,
      respectively-are among the latest in the category of "techno-pathology" to
      receive global attention. This study was conducted with the aim to estimate the
      prevalence of such sensations among medical interns and their association with
      perceived stress levels and smartphone usage pattern. Materials and Methods:
      Ninety-three medical interns using smartphone were recruited for the study. Data
      were collected anonymously using semi-structured questionnaire, perceived stress
      scale (PSS), and smartphone addiction scale-short version (SAS-SV). Data were
      analyzed using descriptive statistics, Chi-square test, independent t-test,
      ANOVA, and Pearson's correlation coefficient. Results: Fifty-nine percent
      students had a high level of stress, whereas 40% had problematic smartphone use.
      Sixty percent students experienced PV, whereas 42% experienced PR and both were
      significantly associated with higher frequency of phone use and the use of
      vibration mode. Mean SAS-SV score was significantly lower in students who did not
      perceive PR/PV, whereas mean PSS score was significantly lower in students who
      did not perceive PV. Conclusion: This study confirms findings from other national
      and international researches about the experience of cell phone phantom
      sensations and their relationship with the pattern of phone use and stress level.
      It also brings to light high levels of stress and problematic smartphone use
      among medical students during the internship.

PMID- 30275620
TI  - Addiction-like Behavior Associated with Mobile Phone Usage among Medical Students
      in Delhi.
AB  - Background: Mobile phone addiction is a type of technological addiction or
      nonsubstance addiction. The present study was conducted with the objectives of
      developing and validating a mobile phone addiction scale in medical students and
      to assess the burden and factors associated with mobile phone addiction-like
      behavior. Materials and Methods: A cross-sectional study was conducted among
      undergraduate medical students aged >=18 years studying in a medical college in
      New Delhi, India from December 2016 to May 2017. A pretested self-administered
      questionnaire was used for data collection. Mobile phone addiction was assessed
      using a self-designed 20-item Mobile Phone Addiction Scale (MPAS). Data were
      analyzed using IBM SPSS Version 17. Results: The study comprised of 233 (60.1%)
      male and 155 (39.9%) female medical students with a mean age of 20.48 years. MPAS
      had a high level of internal consistency (Cronbach's alpha 0.90). Bartlett's test
      of sphericity was statistically significant (P < 0.0001), indicating that the
      MPAS data were likely factorizable. A principal component analysis found strong
      loadings on items relating to four components: harmful use, intense desire,
      impaired control, and tolerance. A subsequent two-stage cluster analysis of all
      the 20-items of the MPAS classified 155 (39.9%) students with mobile phone
      addiction-like behavior that was lower in adolescent compared to older students,
      but there was no significant difference across gender. Conclusion: Mobile phone
      use with increasing adoption of smartphones promotes an addiction-like behavior
      that is evolving as a public health problem in a large proportion of Indian
      youth.

PMID- 30275621
TI  - Usage of Online Social Networking Sites among School Students of Siliguri, West
      Bengal, India.
AB  - Background and Objective: Social networking sites (SNSs) are online platforms
      that provide individuals with an opportunity to manage their personal
      relationship and remain updated with the world. The primary objective of the
      present research was to find the pattern of school students' SNS usage and its
      influence on their academic performance. Materials and Methods: The setting was
      an English medium school situated in the metropolitan city of Siliguri in West
      Bengal. A pretested and predesigned questionnaire was self-administered
      anonymously by 388 randomly selected students. The data were analyzed using
      appropriate statistics. Results: Three hundred thirty-eight (87.1%) students used
      SNS and spent an increased amount of time on these networks. Addiction was seen
      in 70.7% and was more common in the age group of 17 years and above. Conclusion:
      There is a need to educate students about the ways of using SNS and the perils
      associated with it, to help them understand that though very much in trend, they
      should be used cautiously.

PMID- 30275622
TI  - Internet Use Patterns, Internet Addiction, and Psychological Distress Among
      Engineering University Students: A Study from India.
AB  - Background: Internet addiction (IA) among university engineering students and its
      association with psychological distress can impact their educational progress,
      academic competence, and long-term career goals. Thus, there is a need to
      investigate the IA among engineering students. Objectives: This study was a first
      such attempt to explore internet use behaviors, IA, among a large group of
      engineering students from India, and its association with psychological distress
      primarily depressive symptoms. Methods: One thousand eighty six engineering
      students aged 18-21 years pursuing bachelors in engineering from the south Indian
      city of Mangalore participated in the study. The socio-educational and internet
      use behaviors data sheet was used to gather demographic information and patterns
      of internet use, Internet Addiction Test (IAT) was utilized to assess IA, and
      Self-Report Questionnaire (SRQ-20) assessed psychological distress primarily
      depressive symptoms. Results: Among the total N = 1086, 27.1% of engineering
      students met criterion for mild addictive internet use, 9.7% for moderate
      addictive internet use, and 0.4% for severe addiction to internet. IA was higher
      among engineering students who were male, staying in rented accommodations,
      accessed internet several times a day, spent more than 3 h per day on internet,
      and had psychological distress. Gender, duration of use, time spent per day,
      frequency of internet use, and psychological distress (depressive symptoms)
      predicted IA. Conclusions: A substantial proportion of engineering students have
      IA which can be detrimental for their educational progress in university studies
      and long-term career goals. Early identification and management of IA and
      psychological distress among engineering students is crucial.

PMID- 30275624
TI  - Lives without Roots: Institutionalized Homeless Women with Chronic Mental
      Illness.
AB  - The spiral phenomenon of homelessness and mental ill-health are major growing
      epidemic in both developed and developing countries. Viewing from a socio
      economic-political dimension, homelessness and mental ill-health cause
      detrimental effects on the individuals' lives as well as the nation-building
      process. The condition of women seems to be complex, as the gender perspectives
      are often described in terms of patriarchy and powerlessness. The bi
      directionality of mental illness and homelessness creates a vicious cycle, and
      many women seem to end up in shelter care homes. The scenario of homeless women
      with chronic mental illness reflects the lack of community-based rehabilitation
      efforts and gender-sensitive policy level initiatives.

PMID- 30275623
TI  - A Study of Magnitude and Psychological Correlates of Smartphone Use in Medical
      Students: A Pilot Study with A Novel Telemetric Approach.
AB  - Context: Smartphone use is being investigated as a potential behavioral
      addiction. Most of the studies opt for a subjective questionnaire-based method.
      This study evaluates the psychological correlates of excessive smartphone use. It
      uses a telemetric approach to quantitatively and objectively measure
      participants' smartphone use. Methodology: One hundred forty consenting
      undergraduate and postgraduate students using an Android smartphone at a tertiary
      care teaching hospital were recruited by serial sampling. They were pre-tested
      with the Smartphone Addiction Scale-Short Version, Big five inventory, Levenson's
      Locus of Control Scale, Ego Resiliency Scale, Perceived Stress Scale, and
      Materialism Values Scale. Participants' smartphones were installed with tracker
      apps, which kept track of total smartphone usage and time spent on individual
      apps, number of lock-unlock cycles, and total screen time. Data from tracker apps
      were recorded after 7 days. Results: About 36 % of participants fulfilled
      smartphone addiction criteria. Smartphone Addiction Scale score significantly
      predicted time spent on a smartphone in the 7-day period (beta = 0.234, t =
      2.086, P = 0.039). Predictors for time spent on social networking sites were ego
      resiliency (beta = 0.256, t = 2.278, P = 0.008), conscientiousness (beta = 
      0.220, t = -2.307, P = 0.023), neuroticism (beta = -0.196, t = -2.037, P =
      0.044), and openness (beta = -0.225, t = -2.349, P = 0.020). Time spent gaming
      was predicted by success domain of materialism (beta =0.265, t = 2.723, P =
      0.007) and shopping by ego resiliency and happiness domain of materialism.
      Conclusions: Telemetric approach is a sound, objective method for evaluating
      smartphone use. Psychological factors predict overall smartphone usage as well as
      usage of individual apps. Smartphone Addiction Scale scores correlate with and
      predict overall smartphone usage.

PMID- 30275625
TI  - Low-frequency Repetitive Transcranial Magnetic Stimulation for Treatment of
      Tourette Syndrome: A Naturalistic Study with 3 Months of Follow-up.
AB  - The objective of this study is to report the effects of low-frequency repetitive
      transcranial magnetic stimulation (rTMS) in three patients with medication
      refractory Tourette syndrome (TS) and over 3-month follow-up. A review of
      literature on the use of rTMS for the treatment of TS is also presented. Three
      patients with severe, medication-refractory TS and comorbid obsessive-compulsive
      disorder (OCD) in two of them, received an open-label trial of rTMS at 1 Hz
      frequency for 4-week duration. The first two cases of TS-OCD showed, on average,
      around 57% improvement in Yale Global Tic Severity Scale (YGTSS) scores (65% and
      50%) and 45% improvement in Yale-Brown Obsessive-compulsive Scale (Y-BOCS)
      scores; however, the third case of pure-TS showed marginal improvement of 10%
      only. The improvement in TS-OCD patients with rTMS treatment was maintained at
      the end of 3-month follow-up, with an average reduction of about 49% (58% and
      40%) and 36% observed in YGTSS and Y-BOCS scores, respectively. The present study
      supports the use of low-frequency rTMS to improve tics and OCD symptoms in
      patients with severe, medication-refractory TS-OCD. Further, the beneficial
      effects of rTMS treatment were maintained substantially over 3-month follow-up
      period.

PMID- 30275627
TI  - The Lie Effect: A Factor Responsible for Perceived Therapeutic Response.

PMID- 30275626
TI  - Clinical Utility of Add-On Transcranial Direct Current Stimulation for Binge
      Eating Disorder with Obesity in Schizophrenia.
AB  - Over the recent years, there has been an increasing application of noninvasive
      brain stimulation techniques such as transcranial direct-current stimulation
      (tDCS) to modify eating behaviors in healthy population and persons with eating
      disorders. tDCS is a noninvasive, neuromodulatory intervention which is well
      tolerated and safe. In this case report, we describe the successful application
      of add-on tDCS in a patient with schizophrenia to reduce the craving for food
      that in turn, helped in reversing the weight gain.

PMID- 30275628
TI  - Neuropsychiatric Symptoms as Early Manifestation of Progressive Supranuclear
      Palsy.

PMID- 30275629
TI  - Marchiafava-Bignami Disease Presenting as Acute Psychosis.

PMID- 30275630
TI  - Lacosamide Precipitated Neutropenia in a Patient with Bipolar Disorder and
      Comorbid Epilepsy.

PMID- 30275631
TI  - Internal, External, and Ecological Validity in Research Design, Conduct, and
      Evaluation.
AB  - Reliability and validity describe desirable psychometric characteristics of
      research instruments. The concept of validity is also applied to research studies
      and their findings. Internal validity examines whether the study design, conduct,
      and analysis answer the research questions without bias. External validity
      examines whether the study findings can be generalized to other contexts.
      Ecological validity examines, specifically, whether the study findings can be
      generalized to real-life settings; thus ecological validity is a subtype of
      external validity. These concepts are explained using examples so that readers
      may understand why the consideration of internal, external, and ecological
      validity is important for designing and conducting studies, and for understanding
      the merits of published research.

PMID- 30275632
TI  - Potential of Aqueous Two-Phase Systems for the Separation of Levodopa from
      Similar Biomolecules.
AB  - Background: Levodopa is a precursor of several neurotransmitters, such as
      dopamine, and is used in the treatment of the Parkinson's disease. In this work,
      an alternative strategy was studied to separate levodopa from similar
      biomolecules using aqueous two-phase systems (ATPS). Results: Ternary ATPS
      composed of polyethylene glycol (PEG) 400 or ionic liquids (ILs), citrate buffer
      (K3C6H5O7/C6H8O7) at pH 7.0 and water, and quaternary ATPS composed of PEG 400,
      K3C6H5O7/C6H8O7 at pH 7.0, water and the same ILs at 5 wt%, were studied. The
      respective liquid-liquid phase diagrams were determined at 298 K to appraise the
      mixture compositions required to form two-phase systems, followed by studies of
      the partition of levodopa and structurally similar biomolecules (dopamine, L
      phenylalanine, and L-tyrosine). Their partition coefficients and extraction
      efficiencies have been determined, and the selectivity of the ATPS to separate
      levodopa from the remaining biomolecules evaluated. Conclusion: The results
      obtained indicated that PEG-based ATPS were the most effective to separate
      levodopa from L-phenylalanine while the separation from the other biomolecules
      was better using IL-based ATPS, in particular those based on [P4444]Cl and
      [N4444]Cl, with extraction efficiencies of levodopa to the salt-rich phase
      ranging between 62.7 and 74.0%, and of the remaining biomolecules to polymer/IL
      rich phase up to 91.5%.

PMID- 30275633
TI  - Fostering Clinical-Research Partnerships to Advance Physiotherapy Practice: The
      Role of an Innovative Neuro-Rehabilitation Clinic.

PMID- 30275634
TI  - Incorporating a Cognitive Strategy Approach into an Outpatient Stroke
      Physiotherapy Programme: Case Report.
AB  - Purpose: Cognitive Orientation to daily Occupational Performance (CO-OP) has
      demonstrated an effect on skill performance, compared with the usual outpatient
      rehabilitation, in people living with stroke when implemented by occupational
      therapists. This study explored refining CO-OP for delivery by both occupational
      therapists and physiotherapists. Client Description: Two cases were recruited and
      treated using the CO-OP approach, which augments task-specific training with
      cognitive strategies and guided discovery. Intervention: Case 1 was a 79-year-old
      woman, 31 days after parietal stroke, and Case 2 was a 45-year-old man, 62 days
      after bilateral brain stem stroke. Case 1 withdrew from the study for medical
      reasons. Outcome measures applied were the Canadian Occupational Performance
      Measure, the Stroke Impact Scale (SIS), the Self-Efficacy Gauge, the Berg Balance
      Scale, the Box and Block Test, and the 2-minute walk test. Measures and Outcomes:
      After 10 sessions, Case 2 made gains in most measures, including a 22-point gain
      in the SIS mobility domain. Implications: The therapists reported that the
      combined delivery required additional communication with the patients but was
      feasible. Case 2 reported physical and mobility gains larger than the mean
      changes seen in past CO-OP research. Although these results cannot be
      generalized, findings suggest that the inter-professional application of CO-OP
      warrants further investigation.

PMID- 30275635
TI  - Impact of Course Configuration on 6-Minute Walk Test Performance of People with
      Lower Extremity Amputations.
AB  - Purpose: The configuration of the 6-minute walk test (6MWT) may influence the
      distance walked and comparability of results among subjects and across
      programmes. The purpose of this study was to evaluate the relative and absolute
      test-retest reliability of two 6MWT configurations and to evaluate the agreement
      between these two configurations in users of lower extremity prosthetics.
      Methods: A cross-sectional design was used to analyze data from 25 subjects
      completing in-patient prosthetic rehabilitation (mean age 63.12 [SD 13.77] y; 72%
      male). Two configurations of the 6MWT were examined, and relative and absolute
      test-retest reliabilities were calculated. Bland-Altman plots were constructed to
      evaluate agreement between configurations. Results: The relative test-retest
      reliability was excellent for both Configuration 1 and Configuration 2: ICC 0.97,
      95% CI: 0.93, 0.98, and ICC 0.97, 95% CI: 0.94, 0.99, respectively. Comparable
      values for absolute test-retest reliability were also found. The Bland-Altman
      plot demonstrated a difference of +/-63.92 meters between configurations.
      Conclusions: The two 6MWT configurations had excellent relative and absolute test
      retest reliability, but the results from each configuration do not agree
      sufficiently to make them interchangeable or directly comparable. This highlights
      the importance of explicitly indicating the test configuration for the 6MWT when
      reporting results.

PMID- 30275636
TI  - A Pre-Operative Exercise Intervention Can Be Safely Delivered to People with
      Femoroacetabular Impingement and Improve Clinical and Biomechanical Outcomes.
AB  - Purpose: This study aimed to investigate the effects of a pre-hip arthroscopy
      exercise intervention on hip strength, pain, and function in individuals with
      femoroacetabular impingement (FAI). Methods: A total of 20 individuals with FAI
      completed a 10-week, partially supervised exercise programme; this included three
      phases of increasing resistance and functionality, consisting of four to six
      exercises per phase. Hip strength in all six directions; hip pain; function, as
      measured by the Hip disability and Osteoarthritis Outcome Score (HOOS); and
      objective physical function, as measured by the Timed Stair Climb test, were
      determined before and after the intervention. Results: Maximum isometric hip
      strength significantly increased in abduction (p=0.008), adduction (p=0.021), and
      internal rotation (p=0.006) at follow-up. Increases in flexion, extension, and
      external rotation strength did not reach statistical significance. Self-reported
      HOOS pain (p<0.01) and activities of daily living sub-scale scores (p<0.01)
      significantly improved at follow-up. Timed Stair Climb times (p<0.001) also
      significantly decreased at follow-up. Conclusion: A 10-week exercise programme
      can be safely completed by adults with FAI before surgery, and statistically
      significant changes in strength, function, and self-reported clinical outcomes
      can be achieved.

PMID- 30275637
TI  - Gluteus Medius and Minimus Muscle Structure, Strength, and Function in Healthy
      Adults: Brief Report.
AB  - Purpose: This article describes gluteus medius and minimus muscle thickness and
      hip abductor strength and function in healthy adults and explores the
      relationships between muscle thickness and function. Methods: Gluteus medius and
      minimus muscle thickness (B-mode ultrasound), isometric hip abductor strength
      (Biodex dynamometer), and lower extremity function (timed Trendelenburg test,
      Five-Times-Sit-to-Stand Test [FTSST], and lateral step-down test) were measured
      in healthy adults using a cross-sectional study design. Results: A total of 22
      subjects were included: 10 men and 12 women, mean age 25.2 (SD 3.1) years, mean
      BMI 22.9 (SD 3.5) kilograms per metre squared. Muscle thickness of the gluteals
      was a mean 3.88 (SD 0.13) centimetres, and mean hip abductor peak torque was 111
      (SD 43) newton-metres. FTSST mean time was 5.3 (SD 0.2) seconds, and median
      scores were 2.0 points for lateral step-down and 90 seconds for timed
      Trendelenburg. No significant relationships were found between gluteal muscle
      thickness and functional tests (rs=-0.28 to 0.37, ps=0.09-0.80) or strength (r=
      0.24, p=0.28). Conclusion: Although hip abductors are key pelvic stabilizers for
      functional movements, gluteal muscle thickness was not associated with strength
      or function. This may be a result of agonist muscle activity, leading to an
      inability to isolate the gluteals, and to the ceiling effects of the functional
      tests.

PMID- 30275638
TI  - Balance Assessment Practices of Saskatchewan Physiotherapists: A Brief Report of
      Survey Findings.
AB  - Purpose: This study was conducted to determine the balance assessment practices
      of physiotherapists in Saskatchewan. Methods: Practising physiotherapists who
      assess and treat adults with balance and mobility impairments were eligible to
      participate in this cross-sectional, online survey. The questions investigated
      the use of balance assessment measures, the balance components assessed, and
      practice area. Results: Of the 72 respondents, most reported regularly assessing
      five or more of the nine balance components listed. Movement observation was the
      most commonly reported measure used, followed by the Berg Balance Scale, single
      leg stance test, and tandem standing/walking. Conclusions: Most physiotherapists
      in Saskatchewan use a variety of tools to assess balance. Gaps in practices
      related to fall prevention were noted in the mismatch between the tools used and
      the components reportedly assessed.

PMID- 30275639
TI  - To Be or Not to Be a Cardiorespiratory Physiotherapist: Factors That Influence
      Career Choice in a Sample of Canadian Physiotherapists.
AB  - Purpose: This study explored the factors that influence choosing or not choosing
      a career in cardiorespiratory physiotherapy (CRP) from the perspective of a group
      of currently practising, experienced physiotherapists in Canada. Methods: A
      modified Dillman approach was used to distribute a cross-sectional, self
      administered, online questionnaire to all eligible members of the
      cardiorespiratory and orthopaedic divisions of the Canadian Physiotherapy
      Association. A total of 438 participants-21 CRP and 417 non-CRP therapists
      completed the survey. The survey response rate was 9.4%. Results: A narrow scope
      of practice (61.9%) and a lack of interest in CRP subject matter (50.1%) were the
      most influential factors deterring the respondents from making CRP their career
      choice. Interest in CRP (81.0%), mentorship (76.2%), access to physical resources
      (76.2%), and inter-professional practice (71.4%) were the most influential
      factors in pursuing a career in CRP. Conclusion: Increasing the awareness of the
      scope of practice for CRP, exposure to positive mentors, and rich practice
      settings are key factors in promoting physiotherapists' specialisation in CRP.

PMID- 30275640
TI  - Exploring Record Keeping, Clinical Reasoning, and Practice Context: Peer
      Assessment Findings from the Perspective of Situational Competence.
AB  - Purpose: The College of Physiotherapists of Ontario developed its peer practice
      assessment (PA) process on the basis of the statutory requirements for quality
      assurance. We previously reported outcomes from physiotherapists who had two PAs.
      The aims of the current research were to identify areas of sub-optimal
      performance on the assessments and explore any associations with the
      physiotherapists' practice context. Methods: We examined scores from the PAs of
      all physiotherapists who had two unrelated PAs between 2004 and 2012 (n=117), and
      we examined assessment reports for those who had specific patterns of sub-optimal
      outcomes (n=22). We conducted qualitative content analysis on the assessment
      reports to identify areas deemed to need improvement and the contexts in which
      the physiotherapists practised. Comparisons of proportions were carried out using
      Fisher's exact test. Results: The most common area of sub-optimal scores was
      record keeping, followed by clinical reasoning as assessed by means of chart
      stimulated recall. Record-keeping deficits were related to either clinical care
      or administrative requirements (e.g., documenting patient consent in the manner
      required by law). At the second PA, record-keeping deficits were predominantly
      administrative. Physiotherapists with sub-optimal outcomes disproportionately
      worked in private practice contexts (p=0.026). Conclusions: Ontario
      physiotherapists generally maintain high-quality practice. Regulatory bodies may
      consider developing support strategies for meeting professional standards that
      take practice context into account.

PMID- 30275643
TI  - What Does Cochrane Say About ... Vestibular Rehabilitation?

PMID- 30275641
TI  - Return to Meaningful Activities After a Multi-Modal Rehabilitation Programme
      among Individuals Who Experience Persistent Dizziness and Debility Longer Than 9
      Months after Sustaining a Concussion: A Case Series.
AB  - Purpose: The authors explored changes in outcome measures and return to
      meaningful life activities in six individuals who participated in a home-based
      multi-modal rehabilitation programme to address persistent dizziness and debility
      that had continued for more than 9 months since a documented concussion. Methods:
      In a case series using a repeated-measures design, changes from pre- to post
      treatment assessments were assessed after a 6-month intervention. The outcome
      measures used were the Rivermead Post-Concussion Symptoms Questionnaire's
      subsidiary scales (RPQ-3, RPQ-13), Dizziness Handicap Inventory (DHI), Activities
      specific Balance Confidence Scale, Functional Gait Assessment, return to work or
      study, and return to activity. Results: Six months after the multi-modal
      rehabilitation programme, statistically significant differences were found on the
      RPQ-3 (p=0.026), RPQ-13 (p=0.037), and DHI (p=0.033). In addition, four
      participants had returned to their previous work, and all six participants had
      been able to return to physical activity. Conclusion: A supervised home
      programme, provided in the context of a multi-modal rehabilitation programme, has
      the potential to improve outcomes even when rehabilitative services are delayed
      and persistent concussion-related symptoms continue for a significant amount of
      time after the onset of a concussion.

PMID- 30275642
TI  - Physical Activity and Sedentary Behaviour of Master of Physical Therapy Students:
      An Exploratory Study of Facilitators and Barriers.
AB  - Purpose: A full 85% of Canadians fail to meet physical activity (PA) guidelines,
      and 69% report being sedentary. Physical therapists are uniquely positioned to
      promote an active lifestyle; thus, we explored the PA and sedentary behaviour
      (SB) of Master of Physical Therapy (MPT) students as well as the associated
      facilitators and barriers. Methods: We used a mixed-methods approach,
      accelerometry and photovoice (a focus group discussion in which participants
      discussed self-selected photographs). Accelerometer data were used to quantify PA
      (light, moderate, and vigorous) and SB. Thematic analysis of the focus group
      discussion was informed by the socio-ecological model. Results: A total of 26% of
      participants met national PA guidelines, and mean daily sedentary time for
      participants was 670.7 (SD 34.4) minutes. Photovoice analysis revealed four main
      themes related to the facilitators of and barriers to PA and SB: (1) priorities
      and life balance, (2) commitment and accountability, (3) environment, and (4) MPT
      programming. Conclusions: A full 74% of participants did not meet the recommended
      PA guidelines; this is concerning given their immanent roles as health care
      professionals. Physical therapists are well prepared to prescribe PA to clients.
      Not only do MPT students need competencies in prescribing PA and exercise, but
      they may also need to be supported in meeting PA guidelines themselves and
      limiting SB throughout their studies.

PMID- 30275644
TI  - Standing at a Critical Nexus in the Evolution of Physiotherapy.

PMID- 30275645
TI  - Self-Management Strategies for Malignant Lymphedema: A Case Report with 1-Year
      and 4-Year Follow-Up Data.
AB  - Purpose: Malignant lymphedema is an accumulation of interstitial fluid caused by
      tumour infiltration or compression of lymphatic vessels. Our objective is to
      describe self-management strategies for malignant lymphedema using a case report.
      Client Description: A 50-year-old woman with advanced breast cancer was referred
      to our centre with a 3-month history of unexplained left-arm edema, subsequently
      diagnosed as malignant lymphedema caused by tumour compression of the axillary
      lymph nodes. Intervention: She undertook a physiotherapist-guided, modified
      lymphedema treatment programme, with self-management interventions including self
      bandaging and exercise. Limb volumes and leisure exercise levels were measured
      over a 1-year period. Data were collected from her follow-up visit 4 years post
      diagnosis of lymphedema. Measures and Outcome: Within the first month, the
      patient's excess limb volume reduced from 26.8% to 5.9% and, 1 year later,
      remained stable at 3%. Over time, her exercise levels increased (1-year follow
      up: 33.5 MET-hours per week). At 4 years, her excess limb volume was 9.7%, and
      exercise levels were at 36 MET-hours per week. Implications: A woman with
      moderate malignant arm lymphedema caused by advanced breast cancer successfully
      adhered to a guided self-management programme and benefited from reduced swelling
      and improved self-reported physical function in the long term. This case provides
      oncology health professionals with knowledge about self-management options for
      malignant lymphedema.

PMID- 30275646
TI  - Neuropathic Pain after Shoulder Arthroplasty: Prevalence, Impact on Physical and
      Mental Function, and Demographic Determinants.
AB  - Purpose: The objectives of this survey study were to provide an estimate of the
      prevalence of neuropathic pain (NP) and to explore the cross-sectional and
      longitudinal group differences postoperatively. Method: A cohort of consecutive
      patients who had undergone total shoulder arthroplasty (TSA), reverse shoulder
      arthroplasty (RSA), or humeral head replacement (HHR) were surveyed within an
      average of 3.8 years after surgery. Questionnaires completed at the time of the
      survey were the Self-Administered Leeds Assessment of Neuropathic Symptoms and
      Signs (S-LANSS) pain scale, the visual analogue scale (VAS) for pain, the Western
      Ontario Osteoarthritis of the Shoulder (WOOS) index, the Patient Health
      Questionnaire-9 (PHQ-9), and a satisfaction questionnaire. Results: Of the 141
      candidates who were invited to participate in the study, 115 patients
      participated (85 TSA, 21 HHR, and 9 RSA), for an 82% response rate. Five patients
      (4%) met the criteria for NP, of whom one had a loosening of the prosthesis and
      required further surgery. Having NP was associated with greater pain (VAS;
      p=0.001), greater depression (PHQ-9; p=0.001), more disability (WOOS; p=0.030),
      and less satisfaction with the surgery (p=0.014). There was no relationship
      between the presence of NP and patients' age, sex, preoperative pain, range of
      motion results, or WOOS scores (p>0.05). Conclusions: Persistent pain of
      neuropathic origin is not common after shoulder arthroplasty, but it is a
      significant contributor to poor mental and physical well-being and thus warrants
      further research.

PMID- 30275647
TI  - Gait Training after Stroke on a Self-Paced Treadmill with and without Virtual
      Environment Scenarios: A Proof-of-Principle Study.
AB  - Purpose: The purpose of this proof-of-principle study was to show that virtual
      reality (VR) technology could be coupled with a self-paced treadmill to further
      improve walking competency in individuals with chronic stroke. Method: A 62-year
      old man with a chronic right hemispheric stroke participated in a treadmill
      walking programme involving first a control (CTL) protocol, then VR training. In
      CTL training, he walked without time constraints while viewing still pictures and
      reacting to treadmill movements similar to those that he would have experienced
      later in VR training. In VR training, he experienced treadmill movements
      programmed to simulate changes encountered in five virtual environments rear
      projected onto a large screen. Training difficulty in nine sessions over 3 weeks
      was increased by varying the time constraints, terrain surface changes, and
      obstacles to avoid. Effects on walking competency were assessed using clinical
      measures (5 m walk test, 6 min walk test, Berg Balance Scale, Activities-specific
      Balance Confidence scale) and questionnaires (Assessment of Life Habits Scale and
      personal appraisal). Results: CTL and VR training resulted in a similar
      progression through the training sessions of total time walked on the treadmill.
      The VR training led to an additional increase in speed as measured by walking 5
      metres as fast as possible and distance walked in 6 minutes, as well as improved
      balance self-efficacy and anticipatory locomotor adjustments. As reported by the
      participant, these improved outcomes transferred to real-life situations.
      Conclusions: Despite the limited potential for functional recovery from chronic
      stroke, an individual can achieve improvements in mobility and self-efficacy
      after participating in VR-coupled treadmill training, compared with treadmill
      training with the same intensity and surface perturbations but without VR
      immersion. A larger scale, randomized controlled trial is warranted to determine
      the efficacy of VR-coupled treadmill training for mobility intervention post
      stroke.

PMID- 30275648
TI  - Gross Motor Outcomes of Children Born Prematurely in Northern Ontario and
      Followed by a Neonatal Follow-Up Programme.
AB  - Purpose: The developing brain of a premature infant is vulnerable to injury. As a
      result, the long-term consequences of a premature birth include motor deficits,
      cognitive and behavioural problems. It is crucial to identify motor dysfunction
      during the preschool period because it interferes with a child's ability to
      explore the world. The goals of this study were to (1) provide preliminary data
      on the gross motor outcomes of children born prematurely and (2) determine the
      proportion and characteristics of the children who had maintained delays over the
      course of follow-up. Method: A retrospective chart review was conducted on all
      infants monitored by a neonatal follow-up programme. Each child was assessed by a
      single physiotherapist from birth until age 2 years. Of the 107 cases identified,
      97 individuals were retained for analysis; they had a mean gestational age of
      31.1 (SD 2.9) weeks and a mean birth weight of 1.66 (SD 0.53) kilograms. Results:
      The majority of children assessed were found to have gross motor outcomes in the
      average range. Children with scores below the average range were most often born
      very preterm (VPT) or moderately preterm (MPT), with very low or low birth
      weight, respectively. A total of 17 participants were referred to physiotherapy
      to address the gross motor delays identified in the follow-up programme; 14 of
      these 17 had previously been identified as delayed and were being monitored. Late
      preterm (LPT) children (n=6) were most often referred, followed by those born
      extremely preterm (EPT) and VPT (n=4). In total, 56 children were identified as
      delayed at one assessment point but were found to be within normal limits by the
      end of the follow-up period. Conclusion: It is important to periodically monitor
      premature children. A longitudinal, population-based study is also needed to
      provide more data on the predictors and long-term motor outcomes of MPT and LPT
      children.

PMID- 30275649
TI  - Let's Talk about the Talk: Exploring the Experience of Discussing Student
      Performance at the Mid- and Final Points of the Clinical Internship.
AB  - Purpose: The purpose of this study was to explore the experiences of
      physiotherapy students and clinical instructors (CIs) when discussing student
      clinical performance at the mid- and final points of clinical internships. The
      objectives were to identify why performance assessment discussions are valuable,
      explore the role of each participant throughout the discussion, identify the
      challenges associated with these discussions, and explore the effect of the
      standardized assessment tool on the discussion. Methods: This study used a
      qualitative descriptive design, consisting of student and CI focus groups in the
      Greater Toronto Area from January to June 2016. Results: All participants (N=29)
      recognized the importance of having face-to-face performance assessment
      discussions in a quiet and private space. Students and CIs agreed that the
      Canadian Physiotherapy Assessment of Clinical Performance helped to structure and
      focus the discussions. Valuable discussions occurred when students were open
      minded and self-reflected on their performance and when CIs were honest and used
      their expertise to guide learning. Other key features included mutual
      preparedness, two-way feedback that was constructive and tangible, and a goal
      setting process. Students described the emotional component of these discussions
      as being challenging, and CIs found it difficult when a student took a more
      passive role in the discussion. Conclusions: Our findings indicate that valuable
      discussions can provide meaningful feedback, strengthen the student-CI
      relationship, and engage the learner in an ongoing and cumulative learning
      process that contributes to professional development.

PMID- 30275650
TI  - Physiotherapists' and Physiotherapy Students' Perspectives on the Use of Mobile
      or Wearable Technology in Their Practice.
AB  - Purpose: Although extensive research has been carried out on the determinants of
      mobile or wearable health care technology (mHealth), as well as on its acceptance
      by patients and other health care providers, very little research has been done
      on physiotherapists' perspectives on the use of mHealth in their current or
      future practice. The aims of this study were to (1) explore the attitudes of
      physiotherapists toward mHealth using a modified technology acceptance model
      questionnaire, (2) understand the applications and delivery paradigms that are
      most desirable, and (3) assess the content validity of the questionnaire. Method:
      The questionnaire was administered online. Participants (n=76) were recruited
      using snowball and convenience sampling. Data were analyzed using factor analysis
      and partial least-squares path modelling. Results: Results indicate that
      perceived usefulness and perceived ease of use were related to early adoptive
      behaviour among participants. We found no evidence that age, gender, experience,
      or practice setting influenced early adoptive behaviour. Participants
      demonstrated favourable attitudes toward mHealth tools in clinical practice.
      Conclusions: This article provides initial insights into factors that are likely
      to be significant determinants of adoption of mHealth among physiotherapists.
      Further work, including qualitative research, will help to identify personal and
      institutional factors that will improve the acceptance of mHealth.

PMID- 30275651
TI  - Simulation Experiences in Canadian Physiotherapy Programmes: A Description of
      Current Practices.
AB  - Purpose: Although health care professional education programmes around the world
      are increasingly using sophisticated simulation technology, the scope of
      simulation use in Canadian physiotherapy programmes is currently undefined. The
      current study explores the definitions of simulation, its current use, and the
      perceived benefits and barriers in Canadian entry-to-practice physiotherapy
      programmes. Method: Using a qualitative, descriptive study approach, we contacted
      Canadian physiotherapy programmes to identify faculty members with simulation
      experience. Using a semi-structured interview format, we asked participants to
      discuss their perspectives of simulation in their physiotherapy programmes.
      Interviews were audio recorded, transcribed, and analyzed for themes. Results: Of
      13 eligible Canadian physiotherapy programmes, participants from 8 were
      interviewed. The interviews revealed three major themes: (1) variability in the
      definition of fidelity in simulation, (2) variability in simulation use, and (3)
      the benefits of and barriers to the use of simulation. Conclusions: Variability
      in the definition of fidelity in simulation among Canadian physiotherapy
      programmes is consistent with the current literature, highlighting a spectrum of
      complexity from low fidelity to high fidelity. Physiotherapy programmes are using
      a variety of simulations, with the aim of creating a bridge from theoretical
      knowledge to clinical practice. This study describes the starting point for
      characterizing simulation implementation in Canadian physiotherapy programmes and
      reflects the diversity that exists across the country.

PMID- 30275652
TI  - Variation in the Geographic Distribution of Physiotherapy Student Clinical
      Placements in Rural Saskatchewan.
AB  - Purpose: Rural and remote Saskatchewan has a shortage of physiotherapists.
      Positive student experiences in rural and remote communities may influence
      whether graduates choose to work in these settings. The intention of the first
      full-time, 4-week clinical placement (CP) in the Master of Physical Therapy
      programme at the University of Saskatchewan is to provide clinical experiences in
      rural settings outside Saskatoon and Regina. This study examines the geographic
      distribution of and yearly variation in these CPs to determine whether this
      stated intent is being realized. Method: We analyzed the locations of
      physiotherapy student CPs from 2008 to 2016 using geospatial mapping. Results:
      Spatial patterning using mapping identified variability in the number of rural
      placements in geographical regions in Saskatchewan over a 9-year period. An
      average of 75% of CP experiences occurred in rural locations outside the two
      major cities in Saskatchewan between 2008 and 2016 (ranging from 58% in 2015 to
      84% in 2009). Conclusions: The goal of providing all University of Saskatchewan
      physiotherapy students with a rural experience for their first CP is not being
      met. Securing more CPs in rural settings may have a positive impact on
      recruitment of physiotherapists to these communities.

PMID- 30275653
TI  - Facilitators of and Barriers to Providing Access to Community-Based Exercise
      Programmes for Adults with Post-Stroke Aphasia from the Perspective of Programme
      Representatives.
AB  - Purpose: Individuals with post-stroke aphasia (PSA) engage in inadequate levels
      of physical activity (PA), hindering physical and psychosocial recovery. The
      purpose of this study was to identify the extent to which community-based
      exercise programmes (CBEPs) in the Greater Toronto Area (GTA) are accessible to
      adults living with PSA and the characteristics of such programmes from the
      perspective of CBEP representatives. Methods: A cross-sectional, Web-based survey
      was administered to representatives of CBEPs open to adults post-stroke in the
      GTA to identify the CBEPs' relevant characteristics and perceived facilitators of
      and barriers to accessibility. Results: A total of 17 eligible CBEP
      representatives completed the survey, for a response rate of 32%. The most
      commonly used exercise instructors were personal trainers (8; 47%). Of the 17
      eligible CBEP representatives, 10 (59%) identified a lack of qualified personnel
      as the main barrier to providing access to adults with PSA. Verbal strategies
      were among the most commonly used methods of communication with adults with PSA
      (16; 94%), and written material was the least used (5; 29%). Conclusion:
      Understanding the common facilitators of and barriers to providing adults with
      PSA access to CBEPs will assist programme developers to improve the accessibility
      of CBEPs and facilitate PA in this population.

PMID- 30275655
TI  - What Does Cochrane Say about ... Non-Pharmacological Treatment of Neuropathic
      Pain?

PMID- 30275654
TI  - "A Learned Soul to Guide Me": The Voices of Those Living with Kidney Disease
      Inform Physical Activity Programming.
AB  - Purpose: The purpose of this study was to (a) confirm the barriers to and
      facilitators of physical activity (PA) among persons living with chronic kidney
      disease (CKD) in Ontario and (b) inform the design of a Kidney Foundation of
      Canada Active Living for Life programme for persons living with CKD. Method:
      Adults living with CKD in Ontario were invited to participate in a cross
      sectional survey investigating opinions about and needs for PA programming. The
      32-item survey contained four sections: programme delivery preferences, current
      PA behaviour, determinants of PA, and demographics. Data were summarized using
      descriptive statistics and thematic coding. Results: A total of 63 respondents
      participated. They had a mean age of 56 (SD 16) years, were 50% female, and were
      54% Caucasian; 66% had some post-secondary education. The most commonly reported
      total weekly PA was 90 minutes (range 0-1,050 minutes). Most respondents (84%)
      did not regularly perform strength training, and 73% reported having an interest
      in participating in a PA programme. Conclusion: Individuals living with CKD
      require resources to support and maintain a physically active lifestyle. We
      identified a diversity of needs, and they require a flexible and individualized
      inter-professional strategy that is responsive to the episodic changes in health
      status common in this population.

PMID- 30275656
TI  - A quasi-score statistic for homogeneity testing against covariate-varying
      heterogeneity.
AB  - In statistical modeling, it is often of interest to evaluate non-negative
      quantities that capture heterogeneity in the population such as variances, mixing
      proportions and dispersion parameters. In instances of covariate-dependent
      heterogeneity, the implied homogeneity hypotheses are nonstandard and existing
      inferential techniques are not applicable. In this paper, we develop a quasi
      score test statistic to evaluate homogeneity against heterogeneity that varies
      with a covariate profile through a regression model. We establish the limiting
      null distribution of the proposed test as a functional of mixtures of chi-square
      processes. The methodology does not require the full distribution of the data to
      be entirely specified. Instead, a general estimating function for a finite
      dimensional component of the model that is of interest is assumed but other
      characteristics of the population are left completely unspecified. We apply the
      methodology to evaluate the excess zero proportion in zero-inflated models for
      count data. Our numerical simulations show that the proposed test can greatly
      improve efficiency over tests of homogeneity that neglect covariate information
      under the alternative hypothesis. An empirical application to dental caries
      indices demonstrates the importance and practical utility of the methodology in
      detecting excess zeros in the data.

PMID- 30275657
TI  - Retinopathy of prematurity: it is time to take swift action.

PMID- 30275658
TI  - Development of retinopathy of prematurity.

PMID- 30275659
TI  - Classification of retinopathy of prematurity: from then till now.

PMID- 30275660
TI  - Screening for ROP.

PMID- 30275661
TI  - Treatment of retinopathy of prematurity (ROP).

PMID- 30275662
TI  - Role of neonatal team including nurses in prevention of ROP.

PMID- 30275663
TI  - The role of community health workers in prevention of blindness due to ROP.

PMID- 30275664
TI  - Innovations in technology and service delivery to improve Retinopathy of
      Prematurity care.

PMID- 30275665
TI  - Evolution of ROP screening at Aravind Eye Hospital, Coimbatore - Lessons learnt
      and the way ahead.

PMID- 30275666
TI  - Retinopathy of prematurity in Bangladesh: an overview.

PMID- 30275667
TI  - The restless retina in aggressive posterior retinopathy of prematurity:
      prevention is better than cure.

PMID- 30275668
TI  - Counselling and co-opting parents to get best outcomes.

PMID- 30275669
TI  - The role of advocacy and communication in reducing ROP in India.

PMID- 30275670
TI  - Gut Microbiota, the Ketogenic Diet and Epilepsy.
AB  - Investigators from the Department of Pediatric Neurology at the Children's
      Hospital of Fudan University assessed the gut microbiome in pediatric patients
      with intractable non-lesional epilepsy who were treated with the ketogenic diet
      (KD) comparing differences between responders and non-responders over a period of
      6 months.

PMID- 30275671
TI  - Positive Parenting Moderates the Association between Temperament and Self
      Regulation in Low-Income Toddlers.
AB  - Self-regulation develops rapidly during the toddler years and underlies many
      important developmental outcomes, including social-emotional competence and
      academic achievement. It is important to understand factors that contribute to
      early self-regulation skills among children at risk for adjustment difficulties
      in these domains, such as children growing up in poverty. The current study
      examined mother-reported child temperament (negative affect, effortful control)
      and observed maternal parenting (during a mother-child free play) as contributing
      factors to toddlers' observed self-regulation during delay of gratification tasks
      at 27 months (snack delay) and 33 months (gift delay). Participants were 198
      toddlers (M age = 27 months; 53% boys; 48% non-Hispanic white) and their mothers
      from low-income families. Mothers' negative parenting characterized by negative
      affect, hostility, and negative control was associated with poorer self
      regulation contemporaneously. Toddlers' lower negative affect and higher
      effortful control predicted better self-regulation at 33 months, but positive
      parenting characterized by positive affect and sensitivity moderated these
      associations at both time points. Specifically, we found a buffering effect of
      high positive parenting among toddlers with a temperamental risk and a
      deleterious effect of low positive parenting despite toddlers' temperamental
      strength. Results highlight the importance of positive parenting for fostering
      the development of self-regulation among toddlers growing up with poverty-related
      and child-level risks.

PMID- 30275672
TI  - Readmission After Elective Ileostomy in Colorectal Surgery Is Predictable.
AB  - Background and Objectives: Patients who undergo colorectal surgery have high
      postoperative morbidity, with ileostomates being the most disadvantaged. Recent
      studies assessing readmission risk factors do not provide a specific prediction
      model and, if so, do not focus on patients who have had colorectal surgery; thus,
      the results of these studies have limited applicability to our specialized
      practice. We wanted to develop a prediction model for readmission within 30 days
      of discharge after ileostomy creation. Methods: Patients who underwent elective
      ileostomy creation from 2013 to 2016 at the University of Florida were included
      in this retrospective study. Factors significantly associated with readmission
      within 30 days after discharge were identified by comparing a cohort that was
      readmitted within 30 days with one that was not. A practical, predictive model
      that stratified a patient's risk of readmission after the index procedure was
      developed. Results: A total of 86 iliostomates were included; of those, 22 (26%)
      were readmitted within 30 days. Factors significantly associated with readmission
      included preoperative steroid use, history of diabetes, history of depression,
      lack of a hospital social worker or postoperative ostomy education, and the
      presence of complications after the index procedure. A model predicting
      readmission within 30 days of discharge that comprised the first 4 factors was
      developed, with a sensitivity of 73% and a specificity of 77%. Conclusion:
      Prediction of readmission in patients who undergo ileostomy creation is possible,
      suggesting interventions addressing predictive factors that may help decrease the
      readmission rate. Prospective validation of the model in a larger cohort is
      needed.

PMID- 30275673
TI  - Trends of Opportunistic Salpingectomy.
AB  - Background and Objectives: This study analyzed the trends of opportunistic
      salpingectomy (OS) accompanied by hysterectomy in a 9-year follow-up period at a
      single institute. Methods: This retrospective cohort study included 1184 women at
      Hualien Tzu Chi Hospital from 2007 to 2015 who underwent hysterectomy performed
      with or without OS. Parameters including patient age, operating time, surgical
      approach, length of hospital stay, and perioperative complications were
      evaluated. Results: There was an increase in the number of hysterectomies with OS
      (from 8% to 80%; P < .001) over the study period. Minimal additional operating
      time was necessary for hysterectomy with OS (3.7 and 3.6 minutes in open and
      laparoscopic surgery, respectively). No significant differences were observed in
      the risks of hospital readmission or blood transfusions between women who
      underwent hysterectomy with OS performed with the open approach and those who
      underwent the procedure using the laparoscopic approach. From 2007 to 2015, the
      proportion of open hysterectomies decreased from 56% to 6%. Conclusion: The
      results of this 9-year follow-up study revealed that, as a cancer prevention
      method, OS seems to be feasible and safe, requires minimal extra time, and does
      not increase the morbidity or long-term sequelae.

PMID- 30275674
TI  - Standardised Sleeve Gastrectomy Without Reinforcement.
AB  - Background and Objectives: Laparoscopic sleeve gastrectomy (LSG) has some unique
      complications, the most concerning of which is sleeve leak. Staple line
      reinforcement (SLR) has been suggested as a means of decreasing the risk of
      sleeve leak, but it increases the cost. However, there is little in the
      literature regarding the effect of standardized operative technique in reducing
      the complications and improving the outcomes in LSG. We sought to demonstrate
      that standardization of the operative procedure and perioperative care is the key
      to an excellent 30-day outcome and that SLR is not necessary to ensure a
      negligible staple line leak and bleeding rate. Methods: A prospectively
      maintained database was analyzed to identify 303 consecutive patients undergoing
      LSG between July 2010 and November 2017. Data on patient demographics, length of
      hospital stay, conversion to open surgery, perioperative complications, and
      mortality were analyzed. Standardized operative technique and postoperative
      protocol were followed in all cases. SLR was not used in any case. Results: Among
      303 cases, there were 15 complications (5%), 5 (1.7%) of which were severe
      (Clavien-Dindo grade >=3a). There were no conversions to open procedure, no
      staple line leaks, and no inpatient deaths in the cohort. No patient was
      readmitted with an early stricture. Conclusions: The use of a standardized
      operative and postoperative protocol led to an excellent early outcome in our LSG
      cases. Standardization may act to obviate the need for routine SLR techniques
      which are associated with a significant financial cost to both patient and
      hospital.

PMID- 30275675
TI  - Robotic Neck Surgery in the Pediatric Population.
AB  - Introduction: Thyroid, parathyroid, and thymus surgeries are traditionally
      performed via a cervical approach. However, robot-assisted procedures can provide
      a safe alternative for neck surgeries. We report our experiences with robotic
      transaxillary and retroauricular approaches in pediatric patients. Case
      Presentation: We conducted a retrospective review of pediatric patients who
      underwent robot-assisted neck surgery by a single surgeon between April 2010 and
      May 2017. Patient demographics and surgical outcomes including operative time,
      incidence of complications, and length of hospital stay were evaluated.
      Management and Outcomes: Nine surgeries in 7 female patients were reviewed (mean
      age, 16.0 +/- 1.58 years; mean body mass index, 22.5 +/- 0.75). Two thyroid
      lobectomies, 2 complete thyroidectomies, 1 subtotal thyroidectomy, 1 thyroid
      lobectomy with thymectomy, 2 subtotal parathyroidectomies with thymectomy, and 1
      dermoid cyst excision were performed. Two surgeries with the retroauricular
      approach had a mean surgical time of 142.0 +/- 6.13 minutes. Seven surgeries with
      the transaxillary approach had a mean surgical time of 146.1 +/- 21.01 minutes.
      There were no reported conversions, permanent vocal cord paralysis, permanent
      hypoparathyroidism, hematoma, or seroma. There was 1 case (11%) of temporary
      shoulder hypoesthesia and 2 cases of temporary vocal cord paresis (22%).
      Discussion: This series on robot-assisted neck surgeries in children describes
      procedures performed with robotic transaxillary and retroauricular approaches. In
      the hands of a high-volume surgeon the techniques are feasible and safe options
      for operations in the neck in a select group of pediatric patients.

PMID- 30275676
TI  - Transoral Endoscopic Thyroidectomy: A Systematic Review of the Practice So Far.
AB  - Background and Objectives: Thyroid disease largely affects young females, but the
      incidence is also increasing among males. In an effort to avoid the scarring of
      the neck that is synonymous with conventional thyroidectomy, endoscopic
      techniques have been developed over the years. The transoral endoscopic approach
      is the latest of these innovations that promises a scarless surgical outcome.
      This review evaluates whether this technique is safe and feasible in live
      patients and outlines the outcomes in published literature so far. Database:
      PubMed, Medline, BioMed Central, Cochrane Library, OVID and Web of Science were
      systematically searched by using a Medical Subject Heading (MeSH)-optimized
      search strategy. The selection of papers followed the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses (PRISMA) guidelines after setting strict
      inclusion and exclusion criteria. Sixteen studies were included in the final
      analysis. Discussion: This systematic review presents cases of 785 patients.
      Surgeons in 15 of the studies used a completely vestibular approach, whereas
      those in the remaining 2 used the floor of the mouth for primary access.
      Conversion to open surgery took place in 1.3%. In total, 4.3% of patients
      experienced transient laryngeal nerve palsy, whereas 0.1% had permanent recurrent
      incidences of the condition. Transient hypocalcemia occurred in 7.4% of cases,
      with no recorded permanent cases. Carbon dioxide embolism occurred in 0.6% of
      cases, and another 0.6% had a deep-seated neck infection. The complication rates
      within the review were deemed acceptable and the overall technique feasible. A
      prospective randomized controlled trial was proposed to compare this technique
      with conventional thyroidectomy.

PMID- 30275677
TI  - Comparison of variations in cornea after one-handed and two-handed coaxial
      phacoemulsification.
AB  - Purpose: To compare corneal variations in patients undergoing one-handed and two
      handed coaxial phacoemulsification. Setting: Eye Institute, Affiliated Hospital
      of Nantong University, Nantong, China. Design: Prospective consecutive
      nonrandomized comparative cohort study. Methods: Patients with cataracts were
      subject to one-handed (one-handed group) or two-handed coaxial
      phacoemulsification (two-handed group). Intraoperative phaco parameters and
      postoperative outcomes, such as visual acuity, surgically induced astigmatism
      (SIA), corneal volume, central corneal thickness, and corneal endothelial cell
      counts/size were compared. Results: No significant differences in the
      intraoperative phaco parameters were noted between the 2 groups. At postoperative
      week 1, visual outcomes were significantly improved in the one-handed compared
      with the two-handed group (all P<0.05). Corneal volume, central corneal
      thickness, and average cell size were significantly decreased in the one-handed
      group compared with two-handed group (all P<0.05), but the aforementioned
      differences were ameliorated at 1 month and 3 months postoperatively. Endothelial
      cell loss was significantly decreased in the one-handed group compared with the
      two-handed group at any follow-up point (all P<0.05). No significant differences
      in SIA on the anterior surface were noted between the 2 groups. SIA on the
      posterior surface was significantly decreased in the one-handed group compared
      with the two-handed group at 1 week postoperatively (P=0.043) but not at 1 month
      and 3 months postoperatively. Conclusion: One-handed phacoemulsification has the
      advantages of less trauma to the cornea and better early visual outcomes compared
      with the two-handed technique.

PMID- 30275678
TI  - 8K ultra-high-definition microscopic camera for ophthalmic surgery.
AB  - Background: We have developed a new compact lightweight 8K ultra-high-definition
      (UHD; 7,680*4,320 pixels) camera and started medical application with an
      ophthalmic surgical microscope which is interchangeable with the conventional
      high-definition (1,920*1,080 pixels)/4K UHD (3,840*2,160 pixels) microscopic
      camera. Methods: We did a feasibility study to apply our 8K UHD microscope in
      cataract surgery, glaucoma surgery and vitreous surgery using pig cadaver eyes.
      The 8K UHD microscope comprises a surgical microscope, a camera adaptor with
      relay lenses, an 8K UHD camera and an 8K UHD LCD to share the 8K UHD images with
      all surgical staff in real time. Results: In ophthalmic surgeries, higher
      resolution images than conventional microscopic cameras were obtained with 8K UHD
      LCD equivalent to the observation through the microscopic eye pieces. Conclusion:
      Based on the results of this feasibility study, clinical trials on human
      ophthalmic surgery using the new 8K UHD microscopic camera should be conducted in
      the near future.

PMID- 30275679
TI  - The safety and efficacy of phaco-sleeve irrigation-assisted hydrodissection
      during femtosecond laser-assisted cataract surgery.
AB  - Femtosecond laser-assisted cataract surgery (FLACS) changes the intraoperative
      environment due to the generation of intracapsular gas that induces a high
      intracapsular volume. Manual hydrodissection (mH) may induce high intracapsular
      pressure (ICP) and additional intracapsular volume, thereby leading to capsular
      block syndrome (CBS). Since the phaco-sleeve irrigation-assisted hydrodissection
      (iH) technique is used to initially groove and split the lens and remove the
      intracapsular gas, this can reduce the intracapsular volume while bypassing the
      intracapsular lens prior to the hydrodissection. As iH uses the phaco tip to
      intentionally vacuum the intraocular fluid for use in inducing the irrigation jet
      from the sleeve side holes, the ICP cannot surpass the set irrigation pressure,
      thereby avoiding CBS. Using this technique, we performed FLACS without CBS in 310
      cataract eyes. Our findings suggest that the iH technique may be beneficial for
      patients by preventing CBS during FLACS.

PMID- 30275680
TI  - Ocular hypotensive effects of prostaglandin analogs in Japanese patients with
      normal-tension glaucoma: a literature review.
AB  - Purpose: This paper aimed to evaluate the intraocular pressure (IOP)-lowering
      effects of prostaglandin analogs (PGAs) in Japanese patients with normal-tension
      glaucoma (NTG) by reviewing the current literature. Methods: In February 2018,
      database searches were performed in PubMed, Embase, ProQuest, and the Japanese
      databases JAPICDOC and JMEDPlus. Studies were sorted into two categories:
      Category 1 consisted of studies of patients with NTG who reported reduced IOP
      values and Category 2 consisted of studies of patients with NTG who had IOP
      values at predosing and a final evaluation point. Search terms included
      ([unoprostone or latanoprost or travoprost or bimatoprost or tafluprost] and
      [glaucoma] and [Japan or Japanese]). The weighted ocular hypotensive efficacy was
      calculated. A scatter plot analysis was performed and a regression equation was
      calculated for each medication. The fitting of each regression equation was
      evaluated by the least squares method. Results: Eleven articles were eligible for
      Category 1 and 25 articles for Category 2. In the rank order of IOP-lowering
      efficacy of PGAs, bimatoprost was the strongest and latanoprost the weakest.
      Travoprost and tafluprost had almost the same level of ocular hypotensive effect,
      and both were stronger than latanoprost. The scatter plot analysis showed that
      all PGAs reduced IOP by 15%-20%. At higher IOP (17-18 mmHg), the ocular
      hypotensive effect was almost the same with latanoprost, travoprost, and
      tafluprost. In contrast, at lower IOP (12-15 mmHg), the IOP reduction with
      latanoprost was weaker than with travoprost or tafluprost. Conclusion: This
      literature review of the ocular hypotensive effects of PGAs in Japanese patients
      with NTG highlighted that PGAs had different ocular hypotensive effects.
      Ophthalmologists should understand the IOP-lowering profiles of various PGAs and
      apply them to patients with NTG on a case-by-case basis. Trial registration: UMIN
      Clinical Trials Registry UMIN000032344.

PMID- 30275681
TI  - Oral kallidinogenase improved visual acuity and maintained chorioretinal blood
      flow levels after treatment for diabetic macular edema.
AB  - Purpose: This study was designed to investigate the therapeutic effects of oral
      kallidinogenase medication as an adjuvant therapy in treating patients with
      diabetic macular edema (DME). Study design: This was a prospective, open-labeled,
      randomized study. Methods: All patients were given posterior sub-Tenon
      triamcinolone acetonide (STTA) injection and focal laser treatment session for
      DME. The patients were subdivided into two groups: 1) those treated with oral
      kallidinogenase for at least 6 months after local treatment (treated group) and
      2) those treated without oral kallidinogenase (untreated group). In this study,
      best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal
      choroidal thickness (SCT), and chorioretinal blood flow level were measured in 17
      patients (19 eyes). Chorioretinal blood flow levels at the disc and macula were
      measured by laser speckle flowgraphy and evaluated using the mean blur rate
      (MBR). These data were measured at baseline and at 1, 3, and 6 months after
      treatment initiation. Results: BCVA at 6 months after treatment significantly
      improved in treated group (P<0.05). But the mean CRT after treatment
      significantly decreased in both groups. There was no significant difference in
      the mean SCT at baseline between the two groups. The mean SCT after treatment in
      treated group was significantly thinner than that before treatment (P<0.05).
      Compared to baseline (100%), MBR at the disc and the macula at 6 months after
      treatment significantly decreased to 84.8% and 86.2%, respectively, in untreated
      group (P<0.05), though it remained unchanged at 98.7% and 99.7% in treated group.
      Conclusion: Oral kallidinogenase medication is useful as an adjuvant therapy to
      enhance the therapeutic effect of STTA in DME patients.

PMID- 30275682
TI  - The ophthalmic fallout in Utah after the Great American Solar Eclipse of 2017.
AB  - Background: Solar retinopathy is a rare ophthalmic disorder resulting from
      sustained viewing of the sun without protective eyewear. Incidence of solar
      retinopathy typically increases following a solar eclipse due to attempted
      visualization of the sun without appropriate eye protection. This paper serves as
      a case series of all available reported cases of solar retinopathy present in
      Utah resulting from the August 21st, 2017 solar eclipse. Methods: Twenty-seven
      patients had presented with concern for vision changes after the solar eclipse
      and six patients had exam findings consistent with solar retinopathy. Of these
      six cases, charts were available for three. Results: The common finding in all
      cases was a central scotoma with a correlating change to the inner segment/outer
      segment junction on optical coherence tomography. Demographically, all three
      patients were young males. Conclusion: This data provides insights on populations
      in Utah at risk for ophthalmic damage and can aid in targeting education programs
      in the future.

PMID- 30275683
TI  - Effects of hydroxyethyl starch 130/0.4 on the kidney tissue of rats with ureteral
      obstruction.
AB  - Objective: This study was conducted since the effects of colloid solutions on the
      renal system remain controversial and need to be adequately studied in animals.
      We aimed to evaluate the effects of hydroxyethyl starch (Voluven) on the kidney
      tissue of rats with late renal failure due to ureteral obstruction. Materials and
      methods: Rats were divided into four groups: Group C, control; Group HES,
      hydroxyethyl starch solution (HES) 130/0.4 (Voluven(r)); Group UUO, unilateral
      ureteral obstruction (UUO); and Group UUO-HES, UUO-HES 130/0.4 (Voluven(r)). In
      the groups with ureteral obstruction, the distal part of the right ureter was
      accessed and sutured through a lower abdominal incision under ketamine
      anesthesia. Any signs of late-stage renal failure were evaluated after three
      weeks. Rats in the HES group and the renal failure-HES group were administered
      with HES 130/0.4 as a single intravenous dose of 20 mL/kg. After a follow-up of
      24 hours, intra-abdominal blood sample was collected, and the rats were
      sacrificed. Biochemical and histopathological parameters were then evaluated.
      Results: Ureteral obstruction significantly increased urea and creatinine levels.
      In addition, when the UUO-HES and HES groups were compared, the administration of
      HES increased urea and creatinine levels in the UUO-HES group. Nitric oxide
      enzyme activity and malondialdehyde levels have significantly increased in the
      UUO groups. In addition, HES significantly increased nitric oxide activity and
      malondialdehyde levels in the UUO-HES group, in comparison with the HES group.
      The activity of caspases 3 and 8 was significantly increased in the UUO groups.
      In addition, HES significantly increased the activity of caspases 3 and 8 in the
      UUO-HES group, in comparison with the HES group. Light microscopy revealed
      significant changes in the UUO groups, especially in the obstructed kidneys.
      Conclusion: If indicated, HES should be used with caution in cases of UUO, but
      not in the cases of bilateral ureteral obstruction. Other aspects of these
      findings, including the clinical significance and practical applications, merit
      further experimental and clinical investigation.

PMID- 30275684
TI  - Glucosamine-paracetamol spray-dried solid dispersions with maximized intrinsic
      dissolution rate, bioavailability and decreased levels of in vivo toxic
      metabolites.
AB  - Purpose: This study is aimed at preparing and testing physicochemical,
      pharmacokinetic and levels of toxic metabolites of paracetamol and glucosamine
      solid dispersions intended for multiple deliveries via the parenteral or per oral
      route. Methods: Solid dispersions were prepared using the spray drying technique
      at different molar ratios of paracetamol and glucosamine. Characterization of the
      solid dispersions was carried out using differential scanning calorimetry (DSC),
      Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning
      electron microscopy (SEM), equilibrium solubility and intrinsic dissolution rate.
      In vivo pharmacokinetics and toxic metabolites of the prepared dispersions were
      evaluated and compared to those of pure drugs and physical mixtures. Results:
      Instant water solubility and more than 7-fold increase in dissolution rate led to
      significantly high plasma drug concentration (>6.5-fold) compared to paracetamol
      alone. More than 2-fold increase in area under the curve from 0 to 24 h from the
      dispersions was noticed on the third day of oral dosing to animals. Lower number
      and concentration followed by the complete disappearance of toxic pathway
      metabolites were observed on second and third days of dosing with solid
      dispersions and physical mixtures, respectively. Conclusions: The spray-dried
      dispersions support safer and more effective delivery of multiple doses of
      paracetamol, leading to an acceleration of its analgesic actions. Synergism
      between the analgesic actions of paracetamol and joint protective actions of
      glucosamine in this combination is expected to facilitate effective treatment of
      persistent pain-related illnesses such as osteoarthritis.

PMID- 30275685
TI  - Comparison of the efficacy and survival analysis of neoadjuvant chemotherapy for
      Her-2-positive breast cancer.
AB  - Purpose: The objective of this research was to compare the short- and long-term
      efficacy of the following four neoadjuvant chemotherapy (NAC) regimens:
      docetaxel/carboplatin/trastuzumab (TCH), docetaxel/epirubicin/cyclophosphamide
      (TEC), Xeloda/epirubicin/cyclophosphamide followed by Xeloda/docetaxel (XEC-XT),
      and 5-fluorouracil/epirubicin/cyclophosphamide followed by docetaxel (FEC-T) in
      human epidermal growth factor receptor-2-positive (Her-2-positive) breast cancer.
      Patients and methods: According to treatment preferences, 139 patients with Her-2
      positive breast cancer were divided into the following four groups: 39 patients
      in the TCH group, 35 patients in the TEC group, 33 patients in the XEC-XT group,
      and 32 patients in the FEC-T group. The primary end points were disease-free
      survival (DFS) and 5-year overall survival (5-year OS). The secondary end points
      were the efficacy and toxicity of NAC. Results: The TCH, TEC, XEC-XT, and FEC-T
      groups demonstrated overall response rates of 87.1%, 74.3%, 75.8%, and 62.5%
      (P=0.031), respectively, and pathological complete response rates of 25.6%,
      18.2%, 20.0%, and 18.2% (P=0.041), respectively. The DFS rates for the TCH, TEC,
      XEC-XT, and FEC-T groups were 84.6%, 62.9%, 65.7%, and 46.9% (P=0.01),
      respectively. The 5-year OS rates for the TCH, TEC, XEC-XT, and FEC-T groups were
      87.2%, 69.7%, 71.4%, and 59.4% (P=0.069), respectively. The mean survival time
      was 59.3 months (TCH group), 53.5 months (TEC group), 55.3 months (XEC-XT group),
      and 52.4 months (FEC-T group). The difference in survival among the four groups
      was statistically significant (P=0.04). Conclusion: In four NAC regimens for the
      treatment of Her-2-positive breast cancer, the TCH group exhibited better DFS and
      5-year OS. The TCH regimen significantly enhanced the pathological complete
      remission rate of NAC with similar side effects compared to the TEC, XEC-XT, and
      FEC-T regimens. In terms of long-term efficacy, the XEC-XT treatment was superior
      to the FEC-T and TEC treatment, and there was no significant difference between
      the FEC-T and TEC groups.

PMID- 30275686
TI  - A targeted therapy for melanoma by graphene oxide composite with microRNA
      carrier.
AB  - Background: Nowadays, the combination of microRNA (miR) is attracting increased
      attention in clinical cancer trials. However, the clinical use of miR is highly
      limited because of certain properties such as instability, low-specificity
      distribution, and metabolic toxicity. Methods: In order to improve the anti-tumor
      efficacy and reduce the side effects of miR in treating melanoma, a combination
      of graphene oxide (GO), chitosan (CS), and a cellular penetrating peptide, MPG,
      was prepared with solid dispersion method in this research. The research has
      analyzed the specific components of nano drug-loading complexes GO-CS and GO-CS
      MPG through characterization research and confirmed the bio-safety of the carrier
      material GO-CS-MPG. Results: The GO-CS-MPG-miR33a/miR199a nano drug-loading
      complex was successfully constructed and its medical effectiveness was verified.
      Through the subcutaneous tumor implantation experiment, an evident effect of the
      drug-loading complex in inhibiting melanoma cells was proven. Conclusion: Results
      suggest that GO-CS-MPG may have potential applications in melanoma therapy.

PMID- 30275687
TI  - A multicomponent frailty intervention for socioeconomically vulnerable older
      adults: a designed-delay study.
AB  - Purpose: The primary aim of this study was to evaluate the effectiveness of a 6
      month multicomponent intervention on physical function in socioeconomically
      vulnerable older adults in rural communities. As secondary aims, we evaluated the
      effectiveness of the intervention on frailty and other geriatric syndromes,
      sustained benefit at 12 months, and baseline characteristics associated with poor
      response. Patients and methods: This designed-delay study was conducted in 187
      adults (mean age: 77 years; 75% women) who were living alone or on a low income
      in three rural regions of Korea. A 24-week multicomponent program that consisted
      of group exercise, nutritional supplementation, depression management,
      deprescribing medications, and home hazard reduction was implemented with a
      planned 6-month interval from August 2015 through January 2017. The primary
      outcome was physical function, measured using the Short Physical Performance
      Battery (SPPB) score (range: 0-12; minimum clinically important difference >=1)
      at 6 months. Secondary outcomes included frailty phenotype, sarcopenia, Mini
      Nutritional Assessment-Short Form score (range: 0-14), Center for Epidemiologic
      Studies-Depression Scale score (range: 0-60), and falls. Results: At 6 months,
      the SPPB score increased by 3.18 points (95% CI: 2.89, 3.48) from baseline. The
      program improved frailty (odds ratio: 0.06; 95% CI: 0.02, 0.16), sarcopenia (odds
      ratio: 0.32; 95% CI: 0.15, 0.68), Mini Nutritional Assessment-Short Form score by
      1.67 points (95% CI: 1.28, 2.06), and Center for Epidemiologic Studies-Depression
      Scale score by -3.83 points (95% CI: -5.26, -2.39), except for fall (rate ratio:
      0.99; 95% CI: 0.69, 1.43). These beneficial effects were sustained at 12 months.
      Body mass index >=27 kg/m2 and instrumental activities of daily living disability
      at baseline were associated with poor improvement in the SPPB score. Conclusion:
      This 24-week multicomponent program had sustained beneficial effects up to 1 year
      on physical function, frailty, sarcopenia, depressive symptoms, and nutritional
      status in socioeconomically vulnerable older adults in rural communities.
      (ClinicalTrials.gov, NCT 02554994).

PMID- 30275688
TI  - The appeal of the Functional Fitness MOT to older adults and health professionals
      in an outpatient setting: a mixed-method feasibility study.
AB  - Purpose: To understand the views and perceptions regarding the Functional Fitness
      MOT (FFMOT), a battery of functional tests followed by a brief motivational
      interview, of both the older people undergoing it and the health professionals
      delivering it. Patients and methods: Physically inactive older adults (n=29)
      underwent the FFMOT and subsequently attended focus groups to share their
      perceptions of it and to discuss the barriers, motivators, health behavior
      change, and scope to improve physical activity (PA) levels. PA levels were
      recorded at baseline and again at 12 weeks together with a post-intervention
      questionnaire concerning behavior change. Participating physiotherapists and
      technical instructors were interviewed. Results: Most participants felt they had
      learned about their abilities and comparisons with their peers, had a change in
      perception about the importance of good balance and strength, and felt the FFMOT
      helped raise their awareness of local and self-directed physical activity
      opportunities. Most felt their awareness of the need for PA had not changed, but
      25% of participants started a new organized PA opportunity. The health
      professionals perceived the FFMOT as being easy to administer, educating, and
      motivating for participants to increase their PA. Space, time, finances, and
      insecurity about having the necessary skills to conduct the FFMOTs were seen as
      barriers in implementing the FFMOT in daily practice. Conclusion: Over half of
      those offered the FFMOT accepted it, suggesting it is appealing. However, most
      participants felt they were already active enough and that their awareness of the
      need for PA had not changed. There were positive perceptions of the FFMOT from
      both professionals and older people, but both felt the FFMOT could be held in a
      community venue. The overall findings suggest that the FFMOT is feasible in the
      clinical setting, but its effectiveness has yet to be determined.

PMID- 30275689
TI  - Proton pump inhibitors use is associated with a lower risk of acute exacerbation
      and mortality in patients with coexistent COPD and GERD.
AB  - Objective: The effect of antacid therapy for patients with COPD and
      gastroesophageal reflux disease (GERD) remains unclear. Patients and methods:
      This nationwide population-based study was conducted using data from Taiwan's
      National Health Insurance Research Database, and enrolled COPD patients with or
      without GERD. Patients with COPD who were not prescribed COPD medications were
      excluded. Patients with GERD who underwent upper gastrointestinal endoscopy or 24
      hour pH monitoring and received at least 1 antacid were enrolled as symptomatic
      GERD group. The primary endpoint was acute exacerbation and mortality. Results:
      This study included 3,485 patients with COPD and symptomatic GERD, and 13,938
      patients with COPD alone and covered 12,806.57 and 56,809.78 person-years,
      respectively, from 2000 to 2011. After multivariate adjustment, symptomatic GERD
      was associated with acute exacerbation (adjusted hazard ratio [HR]: 1.35, 95% CI:
      1.23-1.48, p<0.0001) and mortality (HR: 1.42, 95% CI: 1.25-1.61, p<0.0001). In
      the COPD with symptomatic GERD group, use of proton pump inhibitors was
      associated with a lower risk of acute exacerbation and mortality (acute
      exacerbation, HR 0.31, 95% CI: 0.20-0.50, p<0.0001; mortality, HR 0.36, 95% CI:
      0.20-0.65, p=0.0007), whereas no significant benefit was observed for histamine2
      receptor antagonists. Conclusion: Use of proton pump inhibitors was associated
      with a lower risk of acute exacerbation and mortality in the patients with COPD
      and symptomatic GERD.

PMID- 30275690
TI  - Effect of background long-acting beta2-agonist therapy on the efficacy and safety
      of a novel, nebulized glycopyrrolate in subjects with moderate-to-very-severe
      COPD.
AB  - Background: Phase III studies demonstrated efficacy and safety of nebulized
      glycopyrrolate inhalation solution (GLY) in subjects with COPD. Secondary
      analyses were performed to examine the effect of background long-acting beta2
      agonist (LABA) use on the efficacy and safety of nebulized GLY. Methods: In two
      12-week placebo-controlled studies (GOLDEN 3 and GOLDEN 4) and one 48-week, open
      label active-controlled study (GOLDEN 5), a total of 2,379 subjects were
      stratified by background LABA use (LABA-yes: n=861; LABA-no: n=1,518) and
      randomized to placebo vs GLY 25 or 50 ug twice daily, or GLY 50 ug twice daily vs
      tiotropium (TIO) 18 ug once daily. Lung function, patient-reported outcomes,
      exacerbations, and safety were assessed. Results: Compared with placebo, pooled
      data from the 12-week studies showed significant improvements from baseline with
      GLY 25 and 50 ug across LABA subgroups in trough FEV1 (LABA-yes: 0.101 and 0.110
      L; LABA-no: 0.092 and 0.101 L, respectively; P<0.001) and St George's Respiratory
      Questionnaire total score (SGRQ; LABA-yes: -2.957 and -3.888; LABA-no: -3.301 and
      -2.073, respectively; P<0.05). Incidence of treatment-emergent adverse events
      (TEAEs) was similar in LABA subgroups, and lower in GLY 25 ug vs placebo. In the
      48-week active-controlled study, GLY and TIO both showed improvement from
      baseline across LABA subgroups in FEV1 (LABA-yes: 0.106 and 0.092 L; LABA-no:
      0.096 and 0.096 L, respectively) and in SGRQ total score (LABA-yes: -5.190 and 
      3.094; LABA-no: -4.368 and -4.821, respectively). Incidence of TEAEs was similar
      between GLY and TIO, and across LABA subgroups. Exacerbation rates were similar
      across treatments and LABA subgroups, and cardiovascular events of special
      interest were more frequent in the LABA-no subgroup. Nebulized GLY, combined with
      LABA, did not generate any additional safety signals. Conclusion: Nebulized GLY
      demonstrated efficacy and was well tolerated up to 48 weeks in subjects with COPD
      with/without background LABA.

PMID- 30275691
TI  - The role of plasma N-terminal brain natriuretic pro-peptide in diagnosing elderly
      patients with acute exacerbation of COPD concurrent with left heart failure.
AB  - Introduction: Acute exacerbation of COPD (AECOPD) and left heart failure (LHF)
      commonly exist together in clinical practice. However, the identification of
      AECOPD concurrent with LHF is currently challenging. Our study aimed to
      investigate the role of plasma N-terminal brain natriuretic pro-peptide (NT
      proBNP) in diagnosing elderly patients with AECOPD associated with LHF. Methods
      and results: LHF was diagnosed in patients with AECOPD according to
      echocardiographic criteria, and the levels of NT-proBNP in plasma were measured
      by quantitative electrochemiluminescence assay. Among the 655 patients with
      AECOPD, 158 (24.1%) had comorbid LHF, whether systolic (n=108, 68.4%) or
      diastolic (n=50, 31.6%). The plasma concentrations of NT-proBNP in elderly
      patients with AECOPD associated with LHF were markedly elevated, compared with
      those with only AECOPD (4,542.5 and 763.0 ng/L, respectively, P<0.01). The
      receiver operating characteristic curve indicated a diagnostic cutoff value of
      1,677.5 ng/L of NT-proBNP in plasma for ascertaining the presence of LHF in
      AECOPD, with a sensitivity of 87.9%, a specificity of 88.5%, and an accuracy of
      88.4%. Conclusion: The plasma level of NT-proBNP may be a useful indicator in
      diagnosing AECOPD associated with LHF.

PMID- 30275692
TI  - Altered spontaneous brain activity patterns in strabismus with amblyopia patients
      using amplitude of low-frequency fluctuation: a resting-state fMRI study.
AB  - Objective: Previous studies have demonstrated that strabismus or amblyopia can
      result in markedly brain function and anatomical alterations. However, the
      differences in spontaneous brain activities of strabismus with amblyopia (SA)
      patients still remain unclear. This current study intended to use the amplitude
      of low-frequency fluctuation (ALFF) technique to investigate the intrinsic brain
      activity changes in SA subjects. Patients and methods: A total of 16 patients
      with SA (6 males and 10 females) and 16 healthy controls (HCs; 6 males and 10
      females) similarly matched in age, gender, and education status were recruited
      and examined with the resting-state functional MRI. The spontaneous brain
      activity changes were investigated using the ALFF technique. The receiver
      operating characteristic curve was performed to classify the mean ALFF signal
      values of the SA patients from HCs. The correlations between the ALFF values of
      distinct brain regions and the clinical manifestations in SA patients were
      evaluated in terms of the Pearson's correlation analysis. Results: Compared with
      HCs, SA patients had significantly decreased ALFF in the left cerebellum
      posterior lobe, left middle frontal gyrus, and bilateral thalamus. In contrast,
      SA patients showed increased ALFF values in the right superior frontal gyrus,
      right precuneus, left cuneus, and bilateral precentral gyrus. Nonetheless, there
      was no linear correlation between the mean ALFF values in brain regions and
      clinical features. Conclusion: Diverse brain regions including vision-related and
      motion-related areas exhibited aberrant intrinsic brain activity patterns, which
      imply the neuropathologic mechanisms of oculomotor disorder and vision deficit in
      the SA patients.

PMID- 30275693
TI  - Gender differences in the relationships among neurosteroid serum levels,
      cognitive function, and quality of life.
AB  - Background: Dehydroepiandrosterone (DHEA), its sulfate ester (DHEA-S), and
      pregnenolone are neurosteroids that can be synthesized in the brain. Previous
      studies have hypothesized that these neurosteroids have antiaging, mood
      enhancing, and cognitive-preserving effects; however, these effects may be gender
      specific. Therefore, the purpose of this study was to investigate the gender
      differences in the relationships among neurosteroids (DHEA, DHEA-S, and
      pregnenolone), cognitive function, and quality of life in healthy individuals.
      Method: In this cross-sectional study, we enrolled 47 men (mean age: 32.8 years)
      and 75 women (mean age: 35.4 years) who had no major physical or psychiatric
      illnesses and measured their serum DHEA, DHEA-S, and pregnenolone. Furthermore,
      we evaluated the subjects' cognitive function and quality of life using the Brief
      Assessment of Cognition in Schizophrenia and the World Health Organization
      Quality of Life Scale, respectively. Results: The serum levels of DHEA and DHEA-S
      demonstrated significant gender differences, even after controlling for age
      effect. In the male subjects, the DHEA serum levels were positively correlated
      with three domains of the World Health Organization Quality of Life Scale,
      including physical health, social relations, and environmental dimensions.
      Meanwhile, the DHEA-S levels positively correlated with the performance of
      working memory, and pregnenolone levels had a positive correlation with working
      memory, verbal fluency, and Brief Assessment of Cognition in Schizophrenia
      composite score. However, in the female subjects, we observed a correlation only
      between the serum levels of DHEA-S and working memory. Conclusion: The findings
      of our study indicate that neurosteroids play a vital role in cognitive function
      and quality of life among men but less so among women. Nevertheless, the
      underlying mechanisms of the gender-specific effect of neurosteroids require
      further investigation.

PMID- 30275694
TI  - The microglial activation profile and associated factors after experimental
      spinal cord injury in rats.
AB  - Background: Spinal cord injury (SCI) has imposed a great impact on the quality of
      life of patients due to its relatively young age of onset. The pathophysiology of
      SCI has been proven to be complicated. Microglia plays an important role in
      neuroinflammation and second injuries after SCI. Different environment and other
      factors may determine the microglial activation profile and what role they play.
      However, neither accurate time-course profiles of microglial activation nor
      influence factors have been demonstrated in varied SCI models. Methods: A rat
      compressive SCI model was used. Microglial activation profile and contents of
      inflammatory factors including IL-1beta, IL-6 and TNF-alpha were detected.
      Myelination status as well as levels of iron and glutamate concentration,
      adenosine triphosphate (ATP) and potassium are also assessed. Results: Our
      results showed that the activated microglia participating in immune-mediated
      responses peaked at day 7 post SCI and gradually decreased during the following 3
      weeks. Contrarily, myelination and oligodendroglia showed an opposite trend,
      indicating that microglia may be a key factor partly through inflammatory
      reaction. Iron and glutamate concentration were found to be the highest at day 7
      after SCI while both ATP and potassium reached a low valley at the same time.
      Conclusion: These findings showed a microglial activation profile and the
      alterations of associated factors after experiment SCI model. Moreover, our data
      suggest that high iron and glutamate concentration may be released by damaged
      oligodendroglia and contribute to the activation of microglial after SCI.

PMID- 30275695
TI  - Speech and language profiles in 4- to 6-year-old children with early diagnosis of
      autism spectrum disorder without intellectual disability.
AB  - Purpose: This study aimed to present speech and language data from a community
      representative group of 4- to 6-year-old children with early-diagnosed autism
      spectrum disorder (ASD) without intellectual disability (ID). Methods: The study
      group comprised 83 children 4-6 years of age with ASD without ID. They had been
      diagnosed with ASD before age 4.5 years and had received intervention at a
      specialized habilitation center. At 2-year follow-up, their language abilities
      were evaluated comprehensively by two speech-language pathologists using a
      battery of assessments. Receptive and expressive language and phonology were
      examined. The phonology evaluation included measures of phonological speech
      production and of phonological processing. Results: Results revealed that almost
      60% had moderate-severe language problems. Nearly half exhibited combined
      expressive and receptive language problems, of which a majority also had
      phonology problems. Phonological speech problems were found in 21% of the total
      group. Conclusion: The findings underscore the importance of considering
      speech/language disorders in children with ASD without ID, since they usually
      attend mainstream classes but need specific educational adaptations.

PMID- 30275696
TI  - CBT-I and HT-I group therapy for adults with insomnia in comparison to those with
      insomnia and comorbid depression - a pilot study.
AB  - Purpose: The aim of this study was to examine the effectiveness of a combined
      cognitive-behavioral therapy for insomnia (CBT-I) and hypnotherapy for insomnia
      (HT-I) program for insomnia patients with or without additional depression
      regarding depressive symptoms and various sleep parameters. Patients and methods:
      A sample of 63 patients suffering from insomnia received a six-session sleep
      intervention, which combined cognitive-behavioral and hypnotherapeutical
      elements. Due to violating exclusion criteria, data of 37 patients were analyzed.
      Ten patients had insomnia comorbid with depression, whereas 27 patients had
      insomnia only. Sleep diaries were implemented to measure various sleep
      parameters, whereas depressive symptomatology was assessed with the anxiety and
      depression scale and Symptom-Checklist-90-R at baseline, before and after the
      intervention, as well as at 3-months follow-up. Results: Depressive symptoms
      decreased from pre to post measurement and follow-up for patients with insomnia
      comorbid with depression, whereas scores of patients with only insomnia remained
      relatively on a low level. Both groups showed a significant increase of sleep
      efficiency and a significant decrease of the duration of wake after sleep onset.
      However, only patients with insomnia and depression revealed a significant
      reduction of sleep-onset latency and a higher level of regeneration.
      Nondepressive insomniacs, on the other hand, showed a significant increase of
      performance from post measurement to follow-up. For both groups, no change over
      time was found for number of wake after sleep onset, total sleep time, mood in
      the morning and evening. Conclusion: Combining CBT-I and HT-I is effective in
      reducing depressive symptoms and improving sleep. Therefore, nonresponders to
      other forms of therapy, eg, pharmacological, interpersonal, or cognitive
      behavioral therapy, might benefit from the combined CBT-I/HT-I intervention.

PMID- 30275697
TI  - Automatic epilepsy detection using fractal dimensions segmentation and GP-SVM
      classification.
AB  - Objective: The most important part of signal processing for classification is
      feature extraction as a mapping from original input electroencephalographic (EEG)
      data space to new features space with the biggest class separability value.
      Features are not only the most important, but also the most difficult task from
      the classification process as they define input data and classification quality.
      An ideal set of features would make the classification problem trivial. This
      article presents novel methods of feature extraction processing and automatic
      epilepsy seizure classification combining machine learning methods with genetic
      evolution algorithms. Methods: Classification is performed on EEG data that
      represent electric brain activity. At first, the signal is preprocessed with
      digital filtration and adaptive segmentation using fractal dimensions as the only
      segmentation measure. In the next step, a novel method using genetic programming
      (GP) combined with support vector machine (SVM) confusion matrix as fitness
      function weight is used to extract feature vectors compressed into lower
      dimension space and classify the final result into ictal or interictal epochs.
      Results: The final application of GP-SVM method improves the discriminatory
      performance of a classifier by reducing feature dimensionality at the same time.
      Members of the GP tree structure represent the features themselves and their
      number is automatically decided by the compression function introduced in this
      paper. This novel method improves the overall performance of the SVM
      classification by dramatically reducing the size of input feature vector.
      Conclusion: According to results, the accuracy of this algorithm is very high and
      comparable, or even superior to other automatic detection algorithms. In
      combination with the great efficiency, this algorithm can be used in real-time
      epilepsy detection applications. From the results of the algorithm's
      classification, we can observe high sensitivity, specificity results, except for
      the Generalized Tonic Clonic Seizure (GTCS). As the next step, the optimization
      of the compression stage and final SVM evaluation stage is in place. More data
      need to be obtained on GTCS to improve the overall classification score for GTCS.

PMID- 30275699
TI  - The evolving role of social media in health-care delivery: measuring the
      perception of health-care professionals in Eastern Saudi Arabia.
AB  - Purpose: The objective of this study is to evaluate the perception of health-care
      professionals in Saudi Arabia toward the usages of social media in health-care
      delivery. Methods: In this cross-sectional study, an online-based questionnaire
      was distributed among the health-care professionals residing in the eastern
      region of Saudi Arabia. Their perception toward the uses of social media in
      health-care service delivery was evaluated by analyzing their attitude toward its
      benefits and risks involved. Results: The sample size was 120 participants, and
      80% of them agreed with the benefits of using social networks in health-care
      services and considered that the use of these technologies in the provision of
      health services improves their professional knowledge and is a suitable tool for
      patient education and public health awareness. However, some respondents (20%)
      believed that there are several risks associated with the use of social media,
      such as ethical or legal challenges, the risk to the patient's health status, or
      the breaching of the privacy and confidentiality of the patient. Conclusion: The
      results of this research indicate that social media can be a useful tool by which
      physicians may promote their services and publish general health information.
      However, there are potential problems in the use of social networks that can have
      negative consequences for patients and HCPs. This implies that precautions must
      be taken to avoid ruptures of patient privacy and other risks that can result in
      legal action against health professionals damaging their image and professional
      status. The study also found that the participants are willing to use social
      media for professional purposes.

PMID- 30275698
TI  - Antihypertensive effect of the mineralocorticoid receptor antagonist eplerenone:
      a pooled analysis of patient-level data from comparative trials using regulatory
      approved doses.
AB  - Purpose: Several options are available for the treatment of hypertension;
      however, many treated patients are still not below blood pressure (BP) target.
      Eplerenone, a selective mineralocorticoid receptor antagonist, is an approved
      treatment option for the management of patients with hypertension in a number of
      countries. This patient-level pooled analysis was conducted to document the
      efficacy and safety/tolerability of eplerenone at the dosages approved for use in
      hypertension in comparison to placebo or other approved antihypertensive agents.
      Methods: Seventeen Phase III studies conducted in patients with mild-to-moderate
      hypertension in the Eplerenone Hypertension Clinical Program were reviewed;
      eleven met the selection criteria. The primary endpoint was change from baseline
      in seated diastolic BP and seated systolic BP measured at the end of the study.
      Results: A total of 2,698 patients were included in this per-protocol analysis.
      In patients treated for at least 6 weeks with a stable dose of eplerenone, doses
      of 50 mg daily and 100 mg daily were associated with greater reductions of seated
      systolic BP and seated diastolic BP compared with placebo (P<0.001) and active
      controlled studies (P< 0.033). In the analysis of covariance model testing of the
      contribution of four factors (age, body mass index [BMI], history of
      cardiovascular disease, and diabetes) on the BP lowering effects of eplerenone,
      only BMI and age were associated with small though statistically significant
      changes in BP (<0.2 mmHg). Eplerenone was well tolerated; headache was the most
      common adverse event for patients in any group. Severe hyperkalemia (serum
      potassium level >6.0 mmol/L) occurred in up to 0.4% in the eplerenone groups,
      0.4% in the placebo group, and 0.1% in the active-control group. Conclusion: This
      patient-level pooled analysis provides robust evidence that eplerenone, at 50 mg
      or 100 mg daily, was effective in lowering BP in patients with mild-to-moderate
      hypertension and was well tolerated.

PMID- 30275701
TI  - Feasibility of radical hysterectomy in women with FIGO stage IIB cervical cancer:
      an observation study of 10-year experience in a tertiary center.
AB  - Purpose: Although definitive chemoradiotherapy is considered as a standard of
      care for FIGO stage IIB cervical cancer in many countries, the role of surgery
      remains controversial. We aimed to evaluate the feasibility and outcomes of
      patients with FIGO stage IIB cervical cancer who received radical surgery in
      China. Patients and methods: A total of 74 women with FIGO stage IIB cervical
      cancer were treated with radical hysterectomy, with or without adjuvant
      radio/chemoradiotherapy, at the Obstetrics and Gynecology Hospital of Fudan
      University between 2004 and 2015. Medical charts and clinical data were
      retrospectively reviewed. The Kaplan-Meier method and Cox regression models were
      used for survival analyses. In addition, prognostic nomograms predicting overall
      survival (OS) and progression-free survival (PFS) were constructed. Results:
      Pathological parametrial involvement (PMI) was only identified in 28.3% (21/74)
      of all patients and 47.3% (9/19) of patients without neoadjuvant treatment. Major
      surgical complications, including bladder fistula, intestinal obstruction and
      ureteral injury, were found in 6.8% (5/74) of patients. Although the use of
      imaging technologies including magnetic resonance imaging (MRI)/positron emission
      tomography-computed tomography (PET-CT) has increased after 2010 compared to that
      prior to 2010, the accuracy of MRI/PET-CT in detecting pathological PMI was lower
      than that of physical examination under anesthesia (P<0.05). Neoadjuvant
      treatment was the only risk factor affecting the accuracy of pre- and
      postoperative accordance of PMI (OR: 3.283 [95% CI: 1.363-7.908], P=0.008). The 2
      and 5-year OS rates were 84.1% and 68.9%, respectively, while the 2- and 5-year
      cumulative recurrence rates were 26.9% and 39.9%, respectively. Cox regression
      analyses indicated that pre- and postoperative accordance of PMI, common iliac
      lymph node metastasis and major surgical complications were significant
      prognostic factors for both OS and PFS. Conclusion: Radical hysterectomy might be
      a feasible alternative for FIGO stage IIB cervical cancer. As pre- and
      postoperative accordance of PMI is relatively low, strategies to appropriately
      select patients who will benefit from surgery via pretreatment evaluation need to
      be further investigated.

PMID- 30275700
TI  - Analysis, Nutrition, and Health Benefits of Tryptophan.
AB  - Tryptophan is an essential plant-derived amino acid that is needed for the in
      vivo biosynthesis of proteins. After consumption, it is metabolically transformed
      to bioactive metabolites, including serotonin, melatonin, kynurenine, and the
      vitamin niacin (nicotinamide). This brief integrated overview surveys and
      interprets our current knowledge of the reported multiple analytical methods for
      free and protein-bound tryptophan in pure proteins, protein-containing foods, and
      in human fluids and tissues, the nutritional significance of l-tryptophan and its
      isomer d-tryptophan in fortified infant foods and corn tortillas as well the
      possible function of tryptophan in the diagnosis and mitigation of multiple human
      diseases. Analytical methods include the use of acid ninhydrin, near-infrared
      reflectance spectroscopy, colorimetry, basic hydrolysis; acid hydrolysis of S
      pyridylethylated proteins, and high-performance liquid and gas chromatography
      mass spectrometry. Also covered are the nutritional values of tryptophan
      fortified infant formulas and corn-based tortillas, safety of tryptophan for
      human consumption and the analysis of maize (corn), rice, and soybean plants that
      have been successfully genetically engineered to produce increasing tryptophan.
      Dietary tryptophan and its metabolites seem to have the potential to contribute
      to the therapy of autism, cardiovascular disease, cognitive function, chronic
      kidney disease, depression, inflammatory bowel disease, multiple sclerosis,
      sleep, social function, and microbial infections. Tryptophan can also facilitate
      the diagnosis of certain conditions such as human cataracts, colon neoplasms,
      renal cell carcinoma, and the prognosis of diabetic nephropathy. The described
      findings are not only of fundamental scientific interest but also have practical
      implications for agriculture, food processing, food safety, nutrition, and animal
      and human health. The collated information and suggested research need will
      hopefully facilitate and guide further studies needed to optimize the use of free
      and protein-bound tryptophan and metabolites to help improve animal and human
      nutrition and health.

PMID- 30275702
TI  - Osteopontin promotes cancer cell drug resistance, invasion, and lactate
      production and is associated with poor outcome of patients with advanced non
      small-cell lung cancer.
AB  - Background: Osteopontin (OPN), a member of the small integrin binding ligand N
      linked glycoprotein family, has been analyzed in numerous types of human
      malignancy. Purpose: The present study detected the expression levels of OPN and
      evaluated its role in tumor progression in patients with non-small cell lung
      cancer (NSCLC). Patients and methods: OPN expression levels were detected using
      immunohistochemistry in 101 NSCLC tumors. The mRNA and protein levels have
      significant difference between advanced NSCLC and stage I/II NSCLC. The drug
      resistance, invasive ability and lactate production of NSCLC cancer cell lines
      (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
      Results: Immunostaining indicated that OPN was primarily expressed in the
      cytoplasm of NSCLC cells. Moreover, OPN correlates with NSCLC clinical traits.
      The results demonstrated that OPN expression levels significantly correlated with
      cancer differentiation, distant metastasis and the efficacy of platinum-based
      treatment. Notably, the results identified OPN expression levels as a potential
      factor for predicting the response of cells to first-line platinum-based
      chemotherapy using multivariate analysis, as well as predicting cancer
      differentiation and distant metastasis. Additionally, the abrogation of OPN
      levels reduced lactate production in NSCLC cells and occurred along side with the
      downregulation of lactate dehydrogenase A (LDHA). Conclusion: The results of the
      current study suggest that OPN may be able to predict poor prognosis and
      cisplatin resistance in patients.

PMID- 30275703
TI  - PD1/PDL1 inhibitors for the treatment of advanced urothelial bladder cancer.
AB  - Introduction: Until recently, systemic chemotherapy was the only option for
      treating bladder cancer and outcomes remained dismal. After a long gap of no
      progress for 40 years, immuno-therapy with checkpoint inhibitors (PDL1 and PD1)
      has revolutionized the treatment paradigm of bladder cancer, with five approved
      agents to treat platinum-refractory bladder cancer since the first approval of
      atezolizumab in May 2016. Methods: This review summarizes the most recent data on
      approved checkpoint inhibitors currently used in management of advanced bladder
      cancer. Early- and late-phase trials of the five checkpoint inhibitors
      (pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab) in advanced
      bladder cancer are reviewed in detail. This review also describes the potential
      application of PD1/PDL1 inhibitors in adjuvant and neoadjuvant settings and non
      muscle-invasive bladder cancer, as well as with radiation in muscle-invasive
      bladder cancer treatment. The role of PDL1 and tumor-mutation burden and clinical
      considerations in choosing a particular immunotherapy are also discussed.
      Results: The approved checkpoint inhibitors (PD1 and PDL1 inhibitors) have
      similar efficacy and safety profiles in metastatic platinum-refractory bladder
      cancer, but they vary in dose and frequency and cost burden. However, only
      pembrolizumab has shown superiority over standard chemotherapy in a randomized
      Phase III setting so far. In addition, in the first-line setting for cisplatin
      ineligible patients, both pembrolizumab and atezolizumab are US Food and Drug
      Administration-approved and well tolerated. There is a lack of consensus on the
      utility of testing for PDL1 as a predictive biomarker, as patients with no PDL1
      expression also derive some clinical benefit. Tumor-mutation burden is another
      predictive biomarker, but needs further validation. Conclusion: Immunotherapy has
      offered a glimmer of hope to patients with bladder cancer. The current landscape
      is rapidly evolving, with novel immunotherapy-combination trials to improve
      outcomes further and evaluate predictive biomarkers to help identify patients
      most likely to benefit from such therapies.

PMID- 30275704
TI  - Prognostic value of miR-17-5 p in gastrointestinal cancers: a systematic review
      and meta-analysis.
AB  - Background: There are accumulating studies investigating the aberrant expression
      of microRNAs in tumor patients. As an important member of miR-17/92 cluster, miR
      17-5 p has been identified as a potential prognostic factor for survival in tumor
      patients. We conducted this meta-analysis aimed to assess the effect of miR-17-5
      p as a prognostic biomarker for gastrointestinal tumor patients. Materials and
      methods: Eligible studies were enrolled by searching the online databases of
      PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and
      WanFang Data until September 2017. We calculated pooled hazard ratios (HRs) and
      95% CI of miR-17-5 p for overall survival and disease-free survival. Results: In
      the categorical variable analysis, we identified 11 studies with 1,279 patients.
      The pooled analyses suggested that overexpression of miR-17-5 p may predict poor
      overall survival (HR = 1.86, 95% CI: 1.55-2.25, P<0.001) and disease-free
      survival (HR = 1.43, 95% CI: 1.01-2.03, P=0.046) in patients with
      gastrointestinal tumors. Subgroup analysis showed the pooled HR of overall
      survival was more significant in tissue specimen, Asian patients, and digestive
      tract tumors. But there was no correlation between the outcomes and European
      patients. Conclusions: This meta-analysis suggested that miR-17-5 p has
      predictive effects on overall survival and disease-free survival of patients with
      gastrointestinal tumors.

PMID- 30275705
TI  - Application of weighted gene co-expression network analysis to identify key
      modules and hub genes in oral squamous cell carcinoma tumorigenesis.
AB  - Purpose: Oral squamous cell carcinoma (OSCC) is one of the most common malignant
      diseases worldwide, yet its molecular mechanisms are largely unknown. We aimed to
      construct gene co-expression networks to identify key modules and hub genes
      involved in the pathogenesis of OSCC. Patients and methods: We used dataset
      GSE30784 to construct co-expression networks by weighted gene co-expression
      network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and
      Genomes (KEGG) enrichment analyses were performed by Database for Annotation,
      Visualization and Integrated Discovery (DAVID). Hub genes were screened and
      validated by other datasets. Results: Turquoise and brown modules were found to
      be the most significantly related to tumorigenesis. Functional enrichment
      analysis showed that the turquoise module was associated with cell-cell adhesion,
      extracellular matrix and collagen catabolic process. A total of 10 hub genes
      (MMP1, TNFRSF12A, PLAU, FSCN1, PDPN, KRT78, EVPL, GGT6, SMIM5 and CYSRT1) were
      identified and validated at transcriptional and translational levels. Their
      genetic alteration and survival analysis were also revealed. Conclusion: We
      identified two modules and 10 hub genes, which were associated with the
      tumorigenesis of OSCC. The two modules provided references that will advance the
      understanding of mechanisms of tumorigenesis in OSCC. Moreover, the hub genes may
      serve as biomarkers and therapeutic targets for precise diagnosis and treatment
      of OSCC in the future.

PMID- 30275706
TI  - The predictive ability of plasma ESR1 mutations for the efficacy of endocrine
      therapy in hormone-receptor-positive advanced breast cancer.
AB  - Purpose: The predictive ability of plasma ESR1 mutations for outcomes among
      patients with advanced breast cancer undergoing endocrine therapy (ET) remains
      disputable. We performed a comprehensive meta-analysis of published studies to
      clarify the impact of plasma ESR1 mutations on clinical outcomes for patients
      after subsequent ET. Materials and methods: An electronic search was performed to
      identify eligible studies. Studies analyzing progression-free survival (PFS)
      and/or overall survival (OS) according to plasma ESR1 mutation status after
      subsequent ET were included. HRs were calculated using a fixed- or random-effects
      model according to heterogeneity. Pooled HRs and 95% CIs were used to estimate
      the effects. Results: Six studies including 705 patients with advanced breast
      cancer met the inclusion criteria. The impact of plasma ESR1 mutations on PFS and
      OS after subsequent ET was reported in six studies (seven groups) and two
      studies, respectively. Meta-analysis results showed that the pooled HR for ESR1
      mutations was 1.70 (95% CI, 1.05-2.74; P=0.03) for OS, which was statistically
      significant for predicting poor survival, and 1.56 (95% CI, 1.13-2.14; P=0.006)
      for PFS; however, Begg's and Egger's test results identified the presence of
      bias. The trim-and-fill method was used, and after incorporation of the imputed
      studies, the HR was 1.16 (95% CI, 0.88-1.53, P=0.30) for PFS, which indicates
      that plasma ESR1 mutation had no effect on PFS after subsequent ET. Subgroup
      analysis suggested that plasma ESR1 mutations were correlated with shorter PFS
      (HR, 1.98; 95% CI, 1.12-3.51; P=0.02) in patients subsequently treated with
      aromatase inhibitors (AIs), whereas no association with PFS was observed for
      patients subsequently treated with non-AI ET (HR, 1.08; 95% CI, 0.85-1.38;
      P=0.54) or fulvestrant (HR, 1.03; 95% CI, 0.79-1.34; P=0.83). Conclusion: The
      current meta-analysis demonstrates that plasma ESR1 mutation status is not a
      predictor of ET efficacy for all drugs without distinction in patients with
      hormone-receptor-positive advanced breast cancer. ESR1 mutation predicted a poor
      response to AIs, whereas it was not predictive of non-AI ET efficacy, especially
      for fulvestrant.

PMID- 30275707
TI  - Oldhamianoside inhibits the growth of ovarian cancer both in vitro and in vivo
      via adjusting inflammation and angiogenesis signals.
AB  - Objective: The aim of this study was to determine the effects and possible
      mechanisms of oldhamianoside on the growth of human ovarian cancer both in vitro
      and in vivo. Materials and methods: CCK-8 assay was applied to estimate the
      effect of oldhamianoside on cell proliferation inhibition in vitro. Nude mice
      bearing human ovarian SKOV3 xenograft tumors were treated with oldhamianoside to
      investigate the effects of compound administration on tumor growth in vivo. To
      further investigate the mechanisms of inhibition effects of oldhamianoside on
      ovarian cancer growth in vivo, the levels of TNF-alpha, IL-6, and MCP-1 in plasma
      from the mice were measured by ELISA. Western blot was used to detect the
      expression of angiogenesis- and/or apoptosis-related proteins. Results: We found
      that oldhamianoside treatment inhibited SKOV3 proliferation and growth both in
      vitro and in vivo. Meanwhile, the levels of TNF-alpha, IL-6, and MCP-1 in plasma
      were markedly suppressed in oldhamianoside-treated mice. Additionally,
      oldhamianoside treatment inhibited the expression of VEGF and VEGFR2 and
      decreased the expression of caspase-3 and Bax/Bcl-2 ratio. Conclusion: Our data
      indicate that oldhamianoside has an obvious inhibition effect on SKOV3
      proliferation, and the mechanisms might be related to inhibition of cell growth,
      apoptosis induction, and adjusting the inflammatory response and angiogenesis
      signal.

PMID- 30275708
TI  - Phenformin and metformin inhibit growth and migration of LN229 glioma cells in
      vitro and in vivo.
AB  - Background: Malignant glioma is refractory to conventional treatment,
      highlighting a need to develop novel efficacious therapies. Biguanides, a class
      of oral antidiabetic drug, have been thought to inhibit proliferation and
      metastasis in a variety of cancers. Purpose: The objective of this study was to
      investigate the affections of biguanides, phenformin (Phen) and metformin (Met),
      on growth and migration of glioma cells LN229 in vitro and in vivo. Methods:
      Glioma cells LN229 were treated with Phen or Met, then cell proliferation and
      death were evaluated by MTT assay and PI stain, and cell cycle were evaluated
      using flow cytometric analysis, meantime wound healing assay and transwell
      migration assay were performed to detect cell migration ability. In addition,
      LN229 were injected in thigh of nude mice, and the mice were treated with Phen or
      Met to detect the effect of Phen and Met in vivo. Results: Phen and Met could
      significantly inhibit cell growth through inhibiting cell proliferation,
      promoting cell death and disturbing cell cycle, and these drugs also could
      inhibit cell colony formation in glioma cells LN229 in vitro. Meanwhile, both
      Phen and Met could significantly inhibit cell migration of LN229 in vitro,
      through effecting the expression of E-cadherin and Vimentin. In addition, both
      Phen and Met inhibited the growth and migration of LN229 in a tumor xenograft
      model. Furthermore, Phen and Met were associated with the increased level of ROS
      of cell mitochondrial, and ROS inhibitor NAC could significantly rescue the cell
      death induced by Phen and Met. Conclusion: Phen and Met displayed powerful
      antitumor effects of LN229, and our findings powerfully suggest the possibility
      of Phen and Met being used as an adjuvant agent in the treatment of glioma
      patients.

PMID- 30275709
TI  - Upregulation of the alternative splicing factor NOVA2 in colorectal cancer
      vasculature.
AB  - Background: Tumor-specific isoforms generated by alternative splicing (AS) are
      demonstrated to contribute to tumor progression and can represent potential
      biomarkers. NOVA2 is an AS factor that in physiological conditions regulates
      endothelial cells' (ECs) polarity and vessel lumen maturation, likely by
      mediating AS of apical-basal polarity regulators. However, NOVA2 expression in
      tumor ECs and its regulation have never been investigated. Methods: To elucidate
      this, 40 colorectal cancer patients were enrolled and NOVA2 expression was
      investigated by immunohistochemistry in samples bearing both the normal mucosa
      and the tumor tissue. Results: NOVA2 was found expressed in ECs of tumor
      vasculature and, importantly, it was upregulated in tumor ECs with respect to
      normal mucosa ECs in all cases (P<0.001). The same samples analyzed by
      immunohistochemistry for the expression HIF1alpha, a marker of hypoxia, showed a
      positive and significant association with NOVA2 levels (P=0.045). Of note, NOVA2
      was upregulated by hypoxia also in an in vitro ECs model. Conclusion: Our results
      provide, for the first time, evidence of NOVA2 expression and upregulation in
      tumor ECs and highlight hypoxia as a potential regulatory factor. These findings
      open a completely new perspective to study tumor vasculature and to uncover NOVA2
      as a potential source of biomarkers and therapeutic targets based on AS isoforms.

PMID- 30275710
TI  - Comparison of short-term outcomes between minimally invasive McKeown and Ivor
      Lewis esophagectomy for esophageal or junctional cancer: a systematic review and
      meta-analysis.
AB  - Purpose: Minimally invasive esophagectomy is increasingly performed for
      esophageal or gastroesophageal junctional cancer, with advantages of improved
      perioperative outcomes in comparison with open esophagectomy. McKeown and Ivor
      Lewis are widely used procedures of minimally invasive esophagectomy, and there
      have been controversies on which one is preferred for patients with resectable
      esophageal or junctional cancer. Patients and methods: This review was registered
      at the International Prospective Register of Systematic Reviews (number
      CRD42017075989). Studies in PubMed, Embase, Web of Science, the Cochrane Library,
      and ClinicalTrials.gov were thoroughly investigated. Eligible studies included
      prospective and retrospective studies evaluating short-term outcomes of minimally
      invasive McKeown esophagectomy (MIME) vs minimally invasive Ivor Lewis
      esophagectomy (MILE) in patients with resectable esophageal or junctional tumors.
      Main parameters included anastomotic leak and 30-day/in-hospital mortality.
      Overall incidence rates (ORs)/weighted mean difference (WMD) with 95% confidence
      intervals (CIs) were calculated by employing random-effects models. Results:
      Fourteen studies containing 3,468 cases were included in this meta-analysis. Age,
      male sex, and American Joint Committee on Cancer (AJCC) stage between the 2
      groups were not statistically different. MIME led to more blood loss, longer
      operating time, and longer hospital stay than MILE. MIME was associated with
      higher incidence of pulmonary complications (OR =1.96, 95% CI =1.28-3.00) as well
      as total anastomotic leak (OR =2.55, 95% CI =1.40-4.63), stricture (OR =2.07, 95%
      CI =1.05-4.07), and vocal cord injury/palsy (OR =5.62, 95% CI =3.46-9.14). In
      addition, the differences of R0 resection rate, number of lymph modes retrieved,
      blood transfusion rate, length of intensive care unit stay, incidence of cardiac
      arrhythmia, and Chyle leak between MIME and MILE were not statistically
      significant. Notably, incidence of severe anastomotic leak (OR =1.28, 95% CI
      =0.73-2.24) and 30-day/in-hospital mortality (OR =1.76, 95% CI =0.92-3.36) as
      well as 90-day mortality (OR =2.22, 95% CI =0.71-6.98) between the 2 procedures
      were also not significantly different. Conclusion: This study suggests that MIME
      and MILE are comparable with respect to clinical safety. MILE may be a better
      option when oncologically and clinically suitable. MIME is still a safe
      alternative procedure when clinically indicated. However, this evidence is at
      risk for bias; randomized controlled trials are needed to validate or correct our
      results.

PMID- 30275712
TI  - SNHG8 is identified as a key regulator in non-small-cell lung cancer progression
      sponging to miR-542-3p by targeting CCND1/CDK6.
AB  - Background: Recently, various dynamically expressed lncRNAs are known to play
      critical roles in cancer progression. Small nucleolar RNA host genes (SNHG), a
      stable cytoplasmic lncRNA, which have been widely reported to act as an oncogene
      in non-small cell lung cancer (NSCLC). As an important member of SNHG, SNHG8 have
      been suggested to over-expressed in several cancer disease, while the biological
      function in NSCLC remains unclear. Purpose: Here we investigated the biological
      function and underlying mechanism of SNHG8 in human NSCLC. Patients and methods:
      The relationship between SNHG8 expression and clinicopathologic characteristic in
      NSCLC patients were observed from January 2014 to December 2014 in 120 NSCLC
      patients. The expression of SNHG8 were analyzed by qRT-PCR assay in cancer
      tissues and cells. Cell proliferation ability were detected in NSCLC cells by CCK
      8 assay. Flow cytometric analysis were performed to detected the cell apoptosis
      and cell cycle. Luciferase assay and Western blot assay were performed on NSCLC
      cells to detected the underlying mechanism of SNHG8 in NSCLC. Moreover, Tumor
      xenografts in nude mice were performed to detected the in vivo function of SNHG8.
      Results: SNHG8 was over-expressed in NSCLC tissues and cells. Patients with high
      SNHG8 expression have poorer overall survival (OS) and progression-free survival
      (PFS) than the patients with low SNHG8 expression. SNHG8 knockdown inhibited
      NSCLC cell proliferation in vitro and in vivo, arrested cell cycle in the G0/G1
      phase via targeting miR-542-3p/CCND1/ CDK6, and induced cell apoptosis via
      activation of Caspase-3. Conclusion: SNHG8 negatively regulated miR-542-3p in
      NSCLC progression by regulating downstream effectors including CCND1 and CDK6.
      SNHG8 showed great potential for the application in the treatment of NSCLC.

PMID- 30275711
TI  - LINK-A promotes cell proliferation through the regulation of aerobic glycolysis
      in non-small-cell lung cancer.
AB  - Purpose: Non-small-cell lung cancer (NSCLC) is the one of the most common
      malignancies worldwide, and occurs at a higher frequency in male individuals.
      Little is known about the role of the long intergenic noncoding RNA for kinase
      activation (LINK-A) in NSCLC, so in the present study we assessed its potential
      role on cell proliferation in NSCLC. Methods: Expression levels of LINK-A in
      NSCLC tissues and cell lines were detected by quantitative reverse-transcription
      polymerase chain reaction. LINK-A was knocked down and overexpressed separately
      in A549 cells and NCI-H1299 cells. The effect of LINK-A expression on cell
      proliferation was determined by MTT assay. The correlation between LINK-A and
      hexokinase II (HKII) expression was investigated by Western blot and HKII
      Activity Assay. Glucose consumption and lactate production assay were used to
      investigate the aerobic glycolysis in NSCLC cells. The effect of LINK-A in vivo
      was determined by xenograft assay. Results: LINK-A expression levels were
      increased in NSCLC tissues compared with normal tissues. Moreover, LINK-A
      expression was positively correlated with NSCLC clinicopathological
      characteristics and survival rate, while knockdown of LINK-A reduced NSCLC cell
      proliferation. LINK-A expression was also positively correlated with HKII, and
      NSCLC cells with low LINK-A expression were found to have significantly reduced
      HKII protein expression, accompanied by a reduction in enzyme activity levels.
      Both in vitro and in vivo experiments showed that LINK-A expression affected
      glucose consumption and lactate production through regulation of HKII expression.
      Conclusion: These data suggest that the functions of LINK-A in NSCLC might play a
      key role in tumor progression and that LINK-A could be a promising predictive
      biomarker and potential therapeutic target for NSCLC.

PMID- 30275713
TI  - Efficacy and safety of trastuzumab as maintenance or palliative therapy in
      advanced HER2-positive gastric cancer.
AB  - Background: Human epidermal growth factor receptor 2 (HER2)-positive gastric
      cancer (GC) is a unique subtype of this disease. Few studies focus on the
      feasibility of trastuzumab as maintenance or palliative therapy for patients with
      HER2-positive advanced GC. Patients and methods: We retrospectively analyzed the
      data of 11 patients, evaluated the efficacy and safety of trastuzumab, and
      attempted to investigate the prognostic factors for trastuzumab treatment. Among
      the 11 patients, one achieved partial response (PR), six achieved stable disease
      (SD), and four were evaluated as progressive disease (PD). Results: The overall
      response rate (ORR) was 9.10%, and the disease control rate (DCR) was 63.64%. The
      median overall survival (OS) was 6.10 months, and the median progression-free
      survival (PFS) was 6.10 months. A significant association was found between
      trastuzumab treatment cycles and efficacy (P=0.027), cycles and PFS (P=0.001),
      and cycles and OS (P=0.005). Among the five patients who accepted more than five
      cycles of trastuzumab, the median OS and median PFS achieved 23.83 months and
      14.67 months, respectively. Moreover, we have found the correlation between tumor
      marker changes and efficacy (P=0.002) and HER2 status and PFS (P=0.027). No
      association was found between HER2 status and OS (P=0.597). Conclusion: The most
      common adverse events were left ventricular ejection fraction (LVEF) reduction,
      fatigue, and anorexia. LVEF reduction was found in seven of 11 patients, but the
      absolute decline in the LVEF was within 10% from the baseline. The results of
      this study suggest that trastuzumab is a feasible option as maintenance or
      palliative therapy for patients with HER2-positive metastatic GC.

PMID- 30275714
TI  - Lentivirus-mediated shRNA targeting MUTYH inhibits malignant phenotypes of
      bladder cancer SW780 cells.
AB  - Objectives: MUTYH is a protein-coding gene that takes part in base excision
      repair. Many previous studies have reported that MUTYH is directly related to
      hereditary adenomatous polyposis and colorectal cancer and is also associated
      with other cancers. However, the relationship between MUTYH and bladder cancer
      (BC) is unknown. Materials and methods: The expression of MUTYH and clinical
      characteristics of BC were collected from databases including The Cancer Genome
      Atlas and Cancer Cell Line Encyclopedia. RNA sequencing and quantitative real
      time PCR were used to detect MUTYH expression in SW780 BC cells. The level of
      MUTYH was stably downregulated by lentivirus-mediated vector in SW780 cells. Cell
      proliferation was evaluated using Cell Counting Kit-8 assay and 5-ethynyl-20
      deoxyuridine assay, migration was detected using scratch assay and Transwell
      assay, and apoptosis was determined using ELISA. Results: MUTYH was upregulated
      in BC tissues and SW780 cells and its expression level was positively associated
      with the stage and grade of carcinomas. MUTYH was successfully downregulated in
      SW780 cells by transducing with a lentivirus-mediated shRNA targeting MUTYH.
      MUTYH knockdown inhibited the proliferation and migration and induced apoptosis
      in SW780 cells. Conclusion: Our data suggest that MUTYH is a new participant in
      bladder urothelial carcinoma. MUTYH may play a role as a biomarker and
      therapeutic target in BC.

PMID- 30275716
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/1179554918782477.].

PMID- 30275718
TI  - Doubling the known endemic species diversity of New Caledonian armored scale
      insects (Hemiptera, Diaspididae).
AB  - Fourteen species of armored scale insects are known only from New Caledonia.
      Here, the adult female of fourteen more are described: Agrophaspisansevatae sp.
      n., Aonidiamontikoghis sp. n. , Aonidiapauca sp. n., Fernaldannawhita sp. n.,
      Furcaspiscostulariae sp. n., Greeniellacasuarinae sp. n., Greenielladacrydiae sp.
      n., Lepidosaphesmonticola sp. n., Leptaspispege gen. et sp. n.,
      Leucaspismontikoghis sp. n., Melanaspisnothofagi sp. n., Neomorganianothofagi sp.
      n., Pseudaonidiadugdali sp. n., and Pseudaonidiayateensis sp. n. We note that the
      diversity of New Caledonian armored scale insects appears to have resulted more
      from trans-oceanic dispersal than in situ speciation.

PMID- 30275717
TI  - New record of Epistylishentscheli (Ciliophora, Peritrichia) as an epibiont of
      Procambarus (Austrocambarus) sp. (Crustacea, Decapoda) in Chiapas, Mexico.
AB  - Epibiosis is very common between crustaceans and ciliates where the calcified
      surface of the crustacean body provides a suitable substrate for ciliate
      colonization. The aim of this contribution is to provide data about a new record
      between the epistylid ciliate Epistylishentscheli Kahl, 1935, and the crayfish
      Procambarus (Austrocambarus) sp. The distribution of the epistylid on the
      basibiont body and its cellular/colonial characteristics were analyzed.
      Procambarus (Austrocambarus) sp. harbored colonies of E.hentscheli only on the
      pereiopods. This is the first record of this peritrich ciliate as an epibiont on
      Crustacea, having been previously found on algae and fish.

PMID- 30275715
TI  - Dual inhibitor of PI3K and mTOR (NVP-BEZ235) augments the efficacy of
      fluorouracil on gastric cancer chemotherapy.
AB  - Purpose: NVP-BEZ235 is a recently developed dual inhibitor of PI3K and mTOR and
      shows good inhibitory effects on several types of tumors. However, the efficacy
      of NVP-BEZ235 on gastric cancer therapy remains unclear. This study aimed to
      investigate the potential of NVP-BEZ235 as a new agent to enhance chemotherapy
      for gastric cancer. Methods: Human gastric cancer MKN-45 cells or nude mice
      xenografted with MKN-45 cells were treated by NVP-BEZ235 and fluorouracil (5-FU)
      alone or in combination. The proliferation, invasion, apoptosis, and
      chemoresistance of gastric cancer cells were examined in vivo and in vitro.
      Results: In vitro, combined treatment with NVP-BEZ235 and 5-FU showed synergistic
      inhibitory effects on proliferation, migration, and invasion and synergistic
      stimulating effects on apoptosis of MKN-45 cells. In vivo, NVP-BEZ235 and 5-FU
      synergistically inhibited the growth and induced apoptosis of MKN-45 xenografts.
      Mechanistically, NVP-BEZ235 inhibited PI3K/Akt/mTOR signaling; decreased the
      levels of Bcl-2, MMP9, and VEGF; but increased the levels of Bax and cleaved
      caspase-3 in MKN-45 xenografts. Conclusion: NVP-BEZ235 enhances the antitumor
      efficacy of 5-FU. Therefore, NVP-BEZ235 is a promising agent to enhance
      chemotherapy for gastric cancer.

PMID- 30275719
TI  - The quest for the identity of Orthoceratiumlacustre (Scopoli, 1763) reveals
      centuries of misidentifications (Diptera, Dolichopodidae).
AB  - Recently, a species of Orthoceratium was collected in Greece that differs
      morphologically from the European species commonly presumed to be
      Orthoceratiumlacustre (Scopoli, 1763). Verification of the identity of the Greek
      species through comparison with 460 specimens of Orthoceratium from 17 West
      Palaearctic and one Afrotropical country, and examination of existing type
      material, revealed that the species recognized as O.lacustre in northwestern
      Europe for over 250 years is actually O.sabulosum (Becker, 1907), the other known
      species in the genus, which was originally described from Tunisia. Although the
      types of O.lacustre have been lost, a comparison of the distribution ranges of
      both species in Europe provided evidence that the species collected in Greece is
      conspecific with O.lacustre. Both species have distinct distributions in the West
      Palaearctic, with O.lacustre largely restricted to the northern border of the
      Mediterranean basin, and O.sabulosum more widespread, occurring in northwestern
      Europe, the western, southern, and eastern Mediterranean, the Middle East, and
      the Afrotropical Region (Tanzania). Both species are redescribed and fully
      illustrated, a neotype is designated for O.lacustre and a lectotype for
      O.sabulosum, and a key to males and females is provided. The misidentifications
      that lasted for over two centuries are explained by the omission by previous
      authors to study the type specimens, and inaccuracies in species descriptions and
      keys.

PMID- 30275720
TI  - Description of a Cretaceous amber fossil putatively of the tribe Coprophilini
      (Coleoptera, Staphylinidae, Oxytelinae).
AB  - An unusual and well-preserved fossil staphylinid is described and figured from a
      single specimen in Upper Cretaceous Burmese amber. Gollandiaplanata gen. et sp.
      n. is tentatively placed in the extant oxyteline tribe Coprophilini, although it
      lacks a few characteristic features of present-day members of the group, likely
      indicating it to be either a stem group of the tribe or prove to be distinct
      pending future discoveries. The discovery of this genus suggests that early
      oxytelines were more morphologically diverse during the Cretaceous and their
      evolutionary history was more complicated than previously documented. Tribal
      placement as regards fossil oxyteline taxa is discussed.

PMID- 30275721
TI  - The genus Mercuria Boeters, 1971 in Morocco: first molecular phylogeny of the
      genus and description of two new species (Caenogastropoda, Truncatelloidea,
      Hydrobiidae).
AB  - The western Palearctic freshwater snail genus Mercuria (Caenogastropoda:
      Hydrobiidae) comprises 26 species primarily distributed in lowland localities of
      Western Europe and North Africa. Although this genus in North Africa has received
      considerable attention in terms of species discoveries through morphological
      descriptions, its distribution and phylogenetic patterns remain unknown. Based on
      morphological and mitochondrial DNA (mtCOI) evidence, this study examines the
      three Mercuria species (M.bakeri, M.tingitana, and M.targouasensis) from Morocco
      identified so far. Besides expanding on information regarding the anatomy of
      these species, two new species (M.midarensis sp. n. and M.tensiftensis sp. n.)
      are described for this region and phylogenetic relationships inferred between
      these species and the European M.emiliana and M.similis. All Moroccan and
      European species were recovered as independent entities according to these
      phylogenetic inferences (uncorrected p-distances 2.8-8.5%) and DNA barcode data.
      Moroccan Mercuria species clustered with M.emiliana from Spain, although basal
      relationships within this clade were not well supported. Given that factors such
      as the season when specimens are collected, habitat type, and parasites could be
      responsible for the remarkable intraspecific variation observed in shell and
      penis morphology, it is proposed that the most efficient approach to delimit and
      identify Mercuria species is to combine morphological descriptions with genetic
      data.

PMID- 30275722
TI  - Four new species of Lesticus (Carabidae, Pterostichinae) from China and
      supplementary comments on the genus.
AB  - The genus Lesticus in China was studied, with descriptions of four new species:
      L.auripennis sp. n. (Guangdong: Nanling, 24.93 degrees N, 112.09 degrees E);
      L.bii sp. n. (Xizang: Medog, 29.32 degrees N, 95.34 degrees E); L.xiaodongi sp.
      n. (Yunnan: Yingjiang, 24.71 degrees N, 97.58 degrees E); and L.violaceous sp. n.
      (Yunnan: Yingjiang, 24.71 degrees N, 97.58 degrees E). One new synonym is
      proposed: L.dubius Dubault, Lassalle & Roux, is a junior synonym of L.solidus
      Roux & Shi. An improved key and a catalogue accommodating all known Chinese
      Lesticus species are provided. Species relationships and the evolution of
      endophallic and other characters are preliminarily discussed.

PMID- 30275723
TI  - New chrysilline and aelurilline jumping spiders from Pakistan (Araneae,
      Salticidae).
AB  - Epocillapakhtunkhwa Ali & Maddison, sp. n. and Stenaelurillusmardanicus Ali &
      Maddison, sp. n. are described from Khyber Pakhtunkhwa Province, Pakistan. Noted
      for the first time is the presence in Epocilla of a small bump just anterior to
      the fovea of the carapace, of unknown functional significance, otherwise known in
      the unrelated Opisthoncus L. Koch, 1880 and Cocalus Pocock, 1897. In addition,
      the female of Menemerusnigli Wesolowska & Freudenschuss, 2012 is described for
      the first time.

PMID- 30275724
TI  - Two new species of Hydromedusae from Queensland, Australia (Hydrozoa,
      Leptothecata).
AB  - Two new species of small hydromedusae were found during routine monitoring in
      coastal waters of eastern Australia and are here described. The first,
      Melicertissaantrichardsoni Uribe-Palomino & Gershwin, sp. n., from Moreton Bay,
      Queensland, is placed in its genus because of its possession of both cordyli and
      eight-fold symmetry. It differs from its congeners in two conspicuous features:
      firstly, having small, oval split gonads located adjacent to the base of the
      stomach, and secondly, in its extremely small size at maturity (2 mm bell
      diameter, compared to the next smallest species at 7 mm). Moreover, it possesses
      a unique combination of other characters. This species appears to be endemic to
      Moreton Bay. The second new species, Paraloveniayongalensis Gershwin & Uribe
      Palomino, sp. n., from the Great Barrier Reef, Queensland, is placed in its genus
      because of its two opposite normal tentacles and two opposite marginal clusters
      of cirri. It differs from its congeners primarily in a more rounded body than the
      others; the shape, length, and position of its short spindle-shaped, distal
      gonads; possession of subumbrellar nematocyst clusters; and possession of
      statocysts. These discoveries bring the total number of Melicertissa species to
      eight and the total number of Paralovenia species to three. The discovery of
      these two micromedusae underscores the need for further examination of the often
      ignored minute and/or gelatinous fauna.

PMID- 30275725
TI  - On the molecular and morphological evolution of continental and insular
      Cryptorchestia species, with an additional description of C.garbinii
      (Talitridae).
AB  - Semi-terrestrial talitrid amphipods of the genus Cryptorchestia (sensu Lowry and
      Fanini 2013) associated with freshwater-soaked leaf litter were known to occur in
      inland lakes of Turkey and at the shores of the Black Sea. Before 2013 they had
      been reported as Orchestiacavimana and later as Cryptorchestiacavimana. In our
      phylogenetic tree, inferred from a mitochondrial and nuclear gene dataset
      (cytochrome oxidase I (COI), and histone H3 (H3), respectively), we show that
      these Turkish populations belong to Cryptochestiagarbinii, a common and
      widespread continental species, which is closely related to C.cavimana (endemic
      to Cyprus) and C.ruffoi (endemic to Rhodes). For the Turkish and European
      populations of C.garbinii, we found low levels of both genetic differentiation
      and morphological variation, and an age-related size variability (increasing at
      each moult) of the small lobe in the male gnathopod I merus, the main
      taxonomically diagnostic character for Cryptorchestia. A mainland (C.garbinii)
      versus insular isolation and in situ speciation (C.cavimana, and C.ruffoi) in the
      two east Mediterranean islands of Cyprus and Rhodes is discussed in relation to
      terrestrial Cryptorchestia species endemic to North East Atlantic volcanic
      islands (Azores, Canary Islands, and Madeira). The incorporation of five
      Mediterranean and Atlantic Orchestia species in the Bayesian analysis of the two
      genes (COI, and H3) indicated that both genera Orchestia and Cryptorchestia are
      not monophyletic.

PMID- 30275726
TI  - Biology of Eumacronychia Townsend, with a redescription of E.persolla Reinhard,
      1965 (Diptera, Sarcophagidae).
AB  - The biology of Eumacronychia Townsend is reviewed and Eumacronychiapersolla
      Reinhard, 1965 is redescribed. The male and female habitus as well as the male
      terminalia are documented with focus-stacked photographs, and features separating
      this species from all other species of Eumacronychia are discussed.

PMID- 30275727
TI  - Revision of the Polynemadikobraz species-group with description of a remarkable
      new species from South Africa (Hymenoptera, Chalcidoidea, Mymaridae).
AB  - A new Afrotropical species of Polynema Haliday, 1833 (Hymenoptera: Mymaridae),
      Polynema (Polynema) sagittaria van Noort & Triapitsyn, sp. n., is described and
      illustrated based on specimens collected in the Cape Floral region in south
      western South Africa. This species is morphologically closely related to the
      recently described Polynema (Polynema) dikobraz Triapitsyn, 2017 from Madagascar,
      both species possessing enlarged spine-like microtrichia on the fore wing disc
      that are unique among all the known world fairyflies. This new species belongs to
      the informal dikobraz species-group of the nominate subgenus of Polynema, which
      previously was only known from Madagascar. In addition, P.sagittaria has the
      ovipositor extending ventrally under the mesosoma to well in front of the head,
      in a bow-like curve, and housed in a narrow, anterior elongation of the metasoma,
      the basal sac. Occurrence and possible significance of such a bizarre ovipositor
      in other Mymaridae is discussed. All images and online keys are available on
      www.waspweb.org.

PMID- 30275728
TI  - Youtuus, a new bamboo-feeding genus of the tribe Augilini with two new species
      from China (Hemiptera, Fulgoromorpha, Caliscelidae).
AB  - A new bamboo-feeding planthopper genus Youtuus Chen & Gong, gen. n. with two new
      species Y.erythrus Gong, Yang & Chen, sp. n. and Y.strigatus Gong, Yang & Chen,
      sp. n. (Hemiptera: Fulgoromorpha: Caliscelidae: Ommatidiotinae: Augilini), are
      described and illustrated from China. Keys to the genera of Augilini and the
      species of Youtuus Chen & Gong, gen. n. are given.

PMID- 30275729
TI  - New jumping spiders from the alpine meadows of the Valley of Flowers, western
      Himalayas, India (Araneae, Salticidae).
AB  - Two new jumping spider species: Nandiciusvallisflorum sp. n., (?) and
      Pelleneshimalaya sp. n. (?, ?), are diagnosed, described and illustrated in
      detail. The specimens were collected from the Valley of Flowers, western
      Himalayas, Uttarakhand State of India.

PMID- 30275730
TI  - Morphological and molecular (28S rRNA) data of monogeneans (Platyhelminthes)
      infecting the gill lamellae of marine fishes in the Campeche Bank, southwest Gulf
      of Mexico.
AB  - During the examination of 913 fish specimens belonging to four families in the
      Campeche Bank (Gulf of Mexico), 23 gill ectoparasitic monogenean species were
      found, which belong to three families: Dactylogyridae, Microcotylidae and
      Diclidophoridae. The species Euryhaliotremaamydrum, E.carbuncularium, E.dunlapae,
      E.fajeravilae, E.fastigatum, E.longibaculum, E.paracanthi, E.tubocirrus,
      Haliotrematoidescornigerum, H.gracilihamus, H.heteracantha, H.longihamus,
      H.magnigastrohamus, H.striatohamus, Hamatopedunculariabagre,
      Neotetraonchusbravohollisae, and N.felis (all Dactylogyridae) were found on the
      hosts Lutjanussynagris, L.griseus, Ariopsisfelis, Bagremarinus,
      Archosargusrhomboidalis, and Haemulonplumieri. Additionally,
      Microcotylearchosargi, Microcotyle sp., and Microcotyloidesincisa (all
      Microcotylidae) were found on L.griseus and A.rhomboidalis; finally, Choricotyle
      sp. 1, Choricotyle sp. 2, and Choricotyle sp. 3 (all Diclidophoridae) were found
      on H.plumieri. The prevalence, abundance, mean intensity of infection, and
      supplementary taxonomic revisions for all monogeneans found are provided. Partial
      sequences of the 28S rRNA gene were also obtained for monogeneans of ariid,
      sparid, and haemulid host fishes to explore their systematic position within the
      Monogenea. New locality and host records for some previously described species of
      Euryhaliotrema, Hamatopeduncularia, Microcotyle, and Choricotyle from lutjanid,
      ariid, sparid, and haemulid hosts were reported. The present study adds evidence
      supporting the interoceanic occurrence of the same monogenean species (on
      lutjanids) on the west-east Atlantic and Pacific Oceans (= amphiamerican
      species). As previously suggested, there are at least, two possibilities to
      explain that parasite distribution: differentiation of morphological features in
      these monogeneans have resulted in only slight to insignificant morphological
      changes developing over the extended period of 3.2 mya (when the Isthmus of
      Panama was closing) and/or speciation is only evident at molecular level.

PMID- 30275731
TI  - A new black nightshade (Morelloid clade, Solanum, Solanaceae) from the caatinga
      biome of north-eastern Brazil with a key to Brazilian morelloids.
AB  - Solanumcaatingae sp. nov. is described from the arid caatinga biome of north
      eastern Brazil. It is known from only a few specimens, but these were found
      amongst the many sheets of the widespread circumtropical weed S.americanum Mill.;
      it is possible that more will be found once its distinct nature has been
      recognised. It differs from S.americanum and all other herbaceous black
      nightshades known in Brazil, in its combination of glandular pubescence and shiny
      black fruit with small spreading sepals. The description of S.caatingae brings
      the number of morelloid solanums in Brazil to seven and a key is provided for
      their identification.

PMID- 30275732
TI  - Evidence from checklists for a Holarctic (circumboreal) kingdom of diatoms.
AB  - Published checklists of freshwater diatoms that represent the American Northwest,
      Laurentian Great Lakes, Germany and the South Polar Region were compared
      systematically and the numbers of taxa shared by two or more of these regions
      were noted. There is a higher level of floristic correspondence between the
      American Northwest and Germany (71%) and between the American Northwest and the
      Laurentian Great Lakes (64%) than between the American Northwest and the South
      Polar Region (45%). These findings support a Holarctic Kingdom of diatoms that is
      parallel to the Holarctic Kingdom of flowering plants. Mountains and coastal
      areas and/or inland waters of high salinity may explain why the American
      Northwest and Germany have more taxa in common than the American Northwest and
      the Laurentian Great Lakes. Common riverine diatom taxa in the American Northwest
      are similar to those reported from nationwide monitoring stations. The number of
      truly cosmopolitan species - those found on all continents - is probably less
      than 300. The terms "cosmopolitan", "endemic" and "native" are often misused when
      applied to diatoms and the first two terms always need to be qualified.

PMID- 30275733
TI  - Total evidence phylogeny of Pontederiaceae (Commelinales) sheds light on the
      necessity of its recircumscription and synopsis of Pontederia L.
AB  - A total evidence phylogeny for Pontederiaceae is herein presented based on new
      morphological and previously published molecular data. Our results led us to re
      circumscribe Pontederia to include Monochoria, Pontederia s.s. and the
      polyphyletic Eichhornia. We provide the needed ten new combinations and 16
      typifications, arrange a total of 25 accepted species (six representing re
      established names) in 5 new subgenera. Furthermore, we provide an identification
      key for the two genera accepted by us in Pontederiaceae, an identification key to
      the subgenera, identification keys to the species of each subgenus and
      commentaries on Pontederia s.l., as well as for each subgenus and each species.

PMID- 30275734
TI  - Nomenclatural review of Acalypha (Euphorbiaceae) of the Western Indian Ocean
      Region (Madagascar, the Comoros Archipelago, the Mascarene Islands and the
      Seychelles Archipelago).
AB  - This work presents a critical nomenclatural review of the Acalypha species of the
      Western Indian Ocean Region (Madagascar, the Comoros Archipelago, the Mascarene
      Islands and the Seychelles Archipelago). This is the first treatment of Acalypha
      of Madagascar since Leandri's monograph in 1942. A total of 151 scientific names
      related to Acalypha from this region are treated. We recognise 35 species (28
      native and seven introduced), treat 93 names as synonyms (28 of them for the
      first time) and identify three as doubtful or excluded names. We designate
      lectotypes for 41 names, make two new combinations and propose one new name.

PMID- 30275735
TI  - Taxonomic status of Populuswulianensis and P.ningshanica (Salicaceae).
AB  - Species delimitation in the genus Populus is particularly challenging due to high
      levels of intraspecific polymorphism as well as frequent interspecific
      hybridisation and introgression. In this study, we aimed to examine the taxonomic
      status of Populusningshanica and P.wulianensis using an integrative taxonomy that
      considers multiple operational criteria. We carried out morphometric analyses of
      leaf traits and genetic examinations (including sequence variations at five
      barcoding DNAs and polymorphisms at 14 nuclear microsatellite SSR primers) at the
      population level between them and two closely related species P.adenopoda and
      P.davidiana. Results suggest that P.wulianensis belongs to the polymorphic
      species, P.adenopoda and should be considered as a synonym of the latter.
      P.ningshanica may have arisen as a result on the hybridisation between
      P.adenopoda and P.davidiana and therefore should be treated as P.*ningshanica.
      This study highlights the importance of the integrated evidence in taxonomic
      decisions of the disputed species.

PMID- 30275736
TI  - Togo National Herbarium database.
AB  - This article describes the herbarium database of the University of Lome. The
      database provides a good representation of the current knowledge of the flora of
      Togo. The herbarium of University of Lome, known also as Herbarium togoense is
      the national herbarium and is registered in Index Herbariorum with the
      abbreviation TOGO. It contains 15,000 specimens of vascular plants coming mostly
      from all Togo's ecofloristic regions. Less than one percent of the specimens are
      from neighbouring countries such as Ghana, Benin and Burkina Faso. Collecting
      site details are specified in more that 97% of the sheet labels, but only about
      50% contain geographic coordinates. Besides being a research resource, the
      herbarium constitutes an educational collection. The dataset described in this
      paper is registered with GBIF and accessible at
      https://www.gbif.org/dataset/b05dd467-aaf8-4c67-843c-27f049057b78. It was
      developed with the RIHA software (Reseau Informatique des Herbiers d'Afrique).
      The RIHA system (Chevillotte and Florence 2006, Radji et al. 2009) allows the
      capture of label data and associated information such as synonyms, vernacular
      names, taxonomic hierarchy and references.

PMID- 30275737
TI  - Phrynahamzaoglui Koc & Budak (Caryophyllaceae), a new species from Central
      Anatolia, Turkey.
AB  - A new species Phrynahamzaoglui was discovered in Hekimhan (Turkey, Malatya
      province) where it grows on hillsides. The P.hamzaoglui and P.ortegioides were
      compared with each other in terms of their general morphology and seed
      micromorphology. Description, distribution, illustration and conservation status
      of the new species are given. Seed lateral and surface, cells, anticlinal cell
      walls, periclinal cell walls structures were examined by scanning electron
      microscopy. The images were captured with the 500*, 100*, and 40* objective lens
      for the details.

PMID- 30275738
TI  - A series of unfortunate events: the forgotten botanist and the misattribution of
      a type collection.
AB  - In 1777, Spain sent The Royal Expedition to Peru and Chile, commonly referred to
      as the "Ruiz and Pavon Expedition", to document the flora of this richly diverse
      part of its colonies. The Expedition was active in the New World for 38 years and
      was led by Hipolito Ruiz and Jose Pavon, who collected in Peru and Chile for the
      first 11 years before returning to Spain to work on publication of the Flora
      Peruviana, et Chilensis. Work on the ground for the reminder of the project in
      Peru and later Ecuador, was continued by Juan Tafalla and Juan Manzanilla. With
      few exceptions, all collections from the Expedition including types, have
      conventionally been attributed to Ruiz and Pavon despite the fact that Tafalla
      and Manzanilla were responsible for a large part of the collections. The purpose
      of this note is to bring to light the important but often overlooked figure of
      Juan Tafalla, to highlight his accomplishments as a collector and to increase
      precision in botanical nomenclature by giving him due credit by correctly
      attributing collections.

PMID- 30275739
TI  - Validation of two Amanita species from eastern North America: A.rhacopus sp. nov.
      and A.variicolor sp. nov.
AB  - Members of the mushroom genus Amanita usually can easily be identified to the
      genus in the field, however, species circumscription and identification are often
      problematic. Several names have been misapplied and cryptic species exist. Here,
      we formally describe and validate two new species of Amanitasect.Vaginatae from
      eastern North America that were recognised under the umbrella European names
      A.ceciliae by past authors: Amanitarhacopus sp. nov. and Amanitavariicolor sp.
      nov.

PMID- 30275740
TI  - Additions to tribe Chromosereae (Basidiomycota, Hygrophoraceae) from China,
      including Sinohygrocybe gen. nov. and a first report of Gloioxanthomycesnitidus.
AB  - Sinohygrocybe gen. nov., typified by S.tomentosipes sp. nov., is described upon
      morphological and molecular evidence. The new genus is characterised by its
      sinuate to subdecurrent or short deccurent, usually furcate and interveined and
      relatively distant lamellae, dry and whitish tomentose stipe, thin-walled
      ellipsoid to oviod, non-constricted basidiospores and particularly elongated
      basidia and a ratio of basidiospore to basidium length of >5 to 8; it is close to
      genera Chromosera and Gloioxanthomyces of the tribe Chromosereae, but
      morphologically differs from Chromosera in less umbilicate basidiomata, tomentose
      stipe and usually longer basidia and differs from Gloioxanthomyces in more robust
      basidioma and less glutinous pileus and/or stipe surface. Phylogenetic analyses,
      with ITS-LSU-RPB2 data, also indicate that Sinohygrocybe forms a very distinct
      and independent clade at the generic level. In addition, a Chinese new record
      G.nitidus is described here.

PMID- 30275741
TI  - A discussion on the genus Fomitiporella (Hymenochaetaceae, Hymenochaetales) and
      first record of F.americana from southern South America.
AB  - Fomitiporella has traditionally been delimited based on the gross morphology of
      the basidiomes, hyphal structure and basdiospores. Recently, phylogenetic studies
      supported the incorporation of an extensive number of species within the genus.
      Although most of its species are nested in the 'Phellinotus clade'
      (Hymenochaetaceae, Basidiomycota), genera such as Arambarria, Inocutis and
      Phellinotus were not included in previous analysis. To further our understanding
      of the genus, new sequences from 28S and ITS nuc rDNA genes were jointly analysed
      with a large selection of taxa in the 'Phellinotus clade', also with re
      examination of morphological and ecological data. Results showed several lineages
      in what has hitherto been considered to represent Fomitiporella, indicating that
      the genus is paraphyletic as presently circumscribed. There is a well-supported
      Fomitiporella core group that includes the type species and nine other
      monophyletic lineages with high support, of which those representing Arambarria,
      Inocutis and Phellinotus are distinct from the Fomitiporella core group by macro
      and micromorphological traits and/or biogeographic distribution.
      Fomitiporellaamericana, a species described from SE USA, was found in the
      Patagonian forests of southern Argentina and Chile; it is the taxon responsible
      for the white heart-rot found on standing Austrocedruschilensis and one of the
      taxa decaying wooden tiles of historic churches in Chiloe Is., Chile.

PMID- 30275742
TI  - Morphological and phylogenetic characterisation of novel Cytospora species
      associated with mangroves.
AB  - Mangroves are relatively unexplored habitats and have been shown to harbour a
      number of novel species of fungi. In this study, samples of microfungi were
      collected from symptomatic branches, stem and leaves of the mangrove species
      Xylocarpusgranatum, X.moluccensis and Lumnitzeraracemosa and examined
      morphologically. The phylogeny recovered supports our morphological data to
      introduce three new species, Cytosporalumnitzericola, C.thailandica and
      C.xylocarpi. In addition, a combined multi-gene DNA sequence dataset (ITS, LSU,
      ACT and RPB2) was analysed to investigate phylogenetic relationships of isolates
      and help in a more reliable species identification.

PMID- 30275743
TI  - Multilocus phylogeny reveals taxonomic misidentification of the
      Schizoporaparadoxa (KUC8140) representative genome.
AB  - Schizoporaparadoxa, current name Xylodonparadoxus, is a white-rot fungus with
      certain useful biotechnological properties. The representative genome of
      Schizoporaparadoxa strain KUC8140 was published in 2015 as part of the 1000
      Fungal Genomes Project. Multilocus phylogenetic analyses, based on three nuclear
      regions (ITS, LSU and rpb2), confirmed a misidentification of S.paradoxa strain
      KUC8140 which should be identified as Xylodonovisporus. This wrong identification
      explains the unexpected geographical distribution of S.paradoxa, since this
      species has a European distribution, whereas the strain KUC8140 was recorded from
      Korea, Eastern Asia.

PMID- 30275745
TI  - Evaluation of a Program of Clean Intermittent Catheterization for Underactive
      Bladder After Radical Hysterectomy.
AB  - Background: Dysfunction of the lower urinary tract is the most common
      complication of radical hysterectomy (RH). However, there are no established
      treatment protocols for postoperative underactive bladder (PUB). We developed our
      own new program for the treatment of underactive bladder (UB) after RH and
      evaluated it retrospectively. Methods: In this program, there are five steps for
      patients to follow according to their urinary condition. The first step is the
      administration of urapidil 30 mg, voiding six times at a predetermined time each
      day, and clean intermittent catheterization (CIC) after each voiding. As the
      patient's condition improves, the number of CICs is reduced, and the medication
      is stopped. The last step includes voiding six times at a predetermined time each
      day. When the volume of residual urine (RU) is less than 100 mL, patients move on
      to the next step. When the volume of RU exceeds 100 mL, patients return to the
      previous step. Results: Of the 75 patients who visited our department, 41 were
      eligible for this program. Twenty-two patients visited our department because of
      urinary retention (UR), and 19 patients were admitted because of increased RU.
      The mean RU volume was 276.3 mL (range, 150-550 mL). After completing the
      program, 39 (95.1%) patients no longer required CIC. The mean time to withdrawal
      of CIC was 25.1 weeks (range, 1-72 weeks). Thirty-six patients no longer required
      medical treatment, including urapidil, for PUB. Of the 5 patients who had
      persistent PUB after treatment, 2 patients continued CIC and urapidil, and three
      patients continued urapidil alone. Conclusion: The present results demonstrate
      that the program of CIC in combination with urapidil is effective for the
      management of PUB after RH.

PMID- 30275744
TI  - Role of Neuroimaging on Differentiation of Parkinson's Disease and Its Related
      Diseases.
AB  - An accurate diagnosis of Parkinson's disease (PD) is a prerequisite for
      therapeutic management. In spite of recent advances in the diagnosis of
      parkinsonian disorders, PD is misdiagnosed in between 6 and 25% of patients, even
      in specialized movement disorder centers. Although the gold standard for the
      diagnosis of PD is a neuropathological assessment, neuroimaging has been playing
      an important role in the differential diagnosis of PD and is used for clinical
      diagnostic criteria. In clinical practice, differential diagnoses of PD include
      atypical parkinsonian syndromes such as dementia with Lewy bodies, multiple
      system atrophy, progressive supranuclear palsy, corticobasal degeneration, caused
      by a striatal dopamine deficiency following nigrostrial degeneration. PD may also
      be mimicked by syndromes not associated with a striatal dopamine deficiency such
      as essential tremor, drug-induced parkinsonism, and vascular parkinsonism.
      Moreover, difficulties are associated with the clinical differentiation of
      patients with parkinsonism from those with Alzheimer's disease. In this review,
      we summarize the typical imaging findings of PD and its related diseases
      described above using morphological imaging modalities (conventional MR imaging
      and neuromelanin MR imaging) and functional imaging modalities (99mTc-ethyl
      cysteinate dimer perfusion single photon emission computed tomography, 123I
      metaiodobenzylguanidine myocardial scintigraphy, and 123I-FP-CIT dopamine
      transporter single photon emission computed tomography) that are clinically
      available in most hospitals. We also attempt to provide a diagnostic approach for
      the differential diagnosis of PD and its related diseases in clinical practice.

PMID- 30275746
TI  - The Acquisition of a New Self-image in Patients with Type 1 Diabetes: A
      Qualitative Study.
AB  - Background: In this study, we aim to highlight the transformation of self-image
      in patients with type 1 diabetes after diagnosis. Our objective in examining the
      self-image of these patients is to provide practical insights for nursing, as
      well as a basic reference for understanding patients. Methods: The participants
      were 15 patients (2 men and 13 women) over 20 years of age who visited an
      outpatient setting to treat type 1 diabetes and had no serious complications, and
      who agreed to participate in the study. Semi-structured interviews were conducted
      1-2 times, with a duration of 60-75 minutes per person, from February 2016 to
      March 2017. We drew on Krippendorff's (1999) content analysis to carry out our
      analysis. Results: We identified a total of 107 codes. The self-image of patients
      with type 1 diabetes was categorized into 8 subcategories and 4 categories. The 4
      categories were 'the wavering of a self-image that is distinct from the past,'
      'loss of former self-image,' 'discovery of a new self-image,' and 'developing a
      new self-image.' Ultimately, we were able to extract a fifth core category,
      'acquisition of a new self-image.' Conclusion: The self-image of patients with
      type 1 diabetes transformed from a negative to a positive one; ultimately,
      patients acquired a new self-image that was congruent with their ideal self
      image. Our results showed that the new self-image that patients acquired through
      various experiences influenced motivation for treatment and continuation of self
      care. When caring for patients with type 1 diabetes, it is crucial for healthcare
      professionals be aware of the meaning that patients derive from their disease and
      related difficulties, as well as to provide care while considering patients' self
      image.

PMID- 30275747
TI  - Qualitative Analysis of the Psychosocial Adaptation Process in Children with
      Chronic Kidney Disease: Toward Effective Support During Transition from Childhood
      to Adulthood.
AB  - Background: Pediatric chronic renal disease only shows abnormal values in a
      urinalysis in the initial stage, and subjective signs and symptoms are rare. If
      adolescents with chronic renal disease face a disease crisis combined with the
      usual developmental crisis, this may cause psychosocial maladaptation. We
      analyzed psychosocial adaptation in Japanese children with chronic renal disease
      in order to identify factors influencing healthy adaptation. Methods: Ten
      children and adult patients with chronic kidney disease attending Tottori
      University Hospital, Japan in 2016 participated in a semi-structured interview (a
      modified version of the grounded theory approach) comprising questions about
      episodes since disease onset and thoughts/feelings at onset. Results: Twenty-four
      concepts extracted from the data were sorted into 5 categories. These concepts
      and categories were expanded on an orthogonal axis with time and self-esteem in
      order to establish an adaptation model for children with chronic kidney disease.
      Category names are as follows. (Cat. 1: Emotional impact on being informed of
      disease, Cat. 2: Social challenges of treatment and resulting identity diffusion,
      Cat. 3: Emotional conflict on school return, Cat. 4: Resilience and related
      factors, Cat. 5: Re-establishment of identity). Conclusion: Since pediatric
      chronic renal disease has few manifestations, it is difficult for patients to
      accept. Children facing a chronic disease crisis plus adolescent developmental
      crisis may show identity diffusion. In order for children to re-establish their
      identity and adapt to society, factors supporting resilience are important. Key
      factors include school life, interactions with friends, counseling by adult
      mentors and family acceptance. Healthcare professionals need to provide age
      appropriate information on renal disease and support patients.

PMID- 30275748
TI  - Therapeutic Value of Lymph Node Dissection Along the Superior Mesenteric Vein and
      the Posterior Surface of the Pancreatic Head in Gastric Cancer Located in the
      Lower Third of the Stomach.
AB  - Background: Therapeutic value of lymph node dissection along the superior
      mesenteric vein (14v) and the posterior surface of the pancreatic head (13)
      remains unclear in gastric cancer patients. Methods: We reviewed 355 patients
      with advanced gastric cancer in the lower third of the stomach who had undergone
      gastrectomy at our hospital. Results: The frequency of lymph node (LN) metastasis
      was 10.2% and 7.4% in stations 13 and 14v, respectively. The frequency of station
      13 metastasis was 26.8% for T3/T4 tumors with group 2 LNs metastasis and 1.4% for
      all other tumors. The frequency of station 14v metastasis was 22.2% for T3/T4
      tumors with group 2 LNs metastasis and 1.8% for all other tumors. The therapeutic
      values for dissecting LN stations 13 and 14v were 1.9 and 0.9, respectively,
      similar to the therapeutic value for group 2 LN dissection. Conclusion: Because
      metastasis to stations 13 and 14v occurs frequently in patients with T3/T4
      gastric cancer located in the lower third of the stomach who also have metastasis
      to group 2 LNs, stations 13 and 14v should be dissected in these patients.

PMID- 30275750
TI  - Less Invasive Surgery for Remnant Stomach Cancer After Esophago-proximal
      Gastrectomy with ICG-guided Blood Flow Evaluation: A Case Report.
AB  - The standard procedure for remnant gastric cancer after esophago-proximal
      gastrectomy is total resection of the remnant stomach considering blood supply.
      However, sometimes surgery may be too invasive due to severe adhesion in the
      thoracic and mediastinal cavity. The blood supply to the remnant stomach depends
      on the right gastroepiploic artery and the right gastric artery. Therefore,
      preservation of the proximal region of the remnant stomach is thought to be
      anatomically impossible. We report a case of remnant gastric cancer that
      developed more than 12 years after lower thoracic esophagectomy plus proximal
      gastrectomy for Siewert Type I squamous cell carcinoma. We used intra-operative
      indocyanine green (ICG) venous-injection to evaluate blood flow and distal
      gastrectomy of the remnant stomach was performed by preserving the proximal
      stomach in the thoracic cavity through an abdominal approach. There were no
      complications of the remnant stomach or the anastomosis to the jejunum after
      surgery. In this case, we focused on the blood supply by collateral circulation
      through the anastomotic line from the remnant esophagus. After confirming blood
      supply with intra-operative evaluation using ICG fluorescence, less-invasive
      distal gastrectomy was successfully performed. As the intra-operative ICG-based
      evaluation for blood supply is a simple and safe method, it might be useful for
      determining the resection margin of various organs and be effective for the
      introduction of less invasive surgery. Here, we report a case and a review of the
      literature.

PMID- 30275749
TI  - Portal Vein Stenting for Portal Vein Stenosis After Pancreatoduodenectomy: A Case
      Report.
AB  - Portal vein stenosis, which results in serious clinical conditions such as
      gastrointestinal variceal bleeding and liver failure, is caused by hepatobiliary
      pancreatic cancer or major postoperative complications after hepatobiliary
      pancreatic surgery. In recent years, portal vein stenting under interventional
      radiology has been applied as a more useful treatment method for portal vein
      stenosis than invasive surgery. We herein report the successful use of a vascular
      stent for portal vein stenosis after pancreatoduodenectomy. A 66-year-old man
      with distal cholangiocarcinoma underwent subtotal stomach-preserving
      pancreatoduodenectomy with resection of the portal vein because of direct
      invasion to the main portal vein at our hospital. The portal vein was
      reconstructed without a venous graft. He developed jejunal bleeding near the
      pancreatojejunostomy on postoperative day (POD) 2. Although embolization of the
      responsible vessel achieved hemostasis, an intraoperatively inserted drainage
      tube was needed for a long period of time postoperatively because the embolized
      afferent jejunum was perforated. He was discharged on POD 39 after removal of the
      drainage tube. On POD 282, he was readmitted with melena and severe fatigue.
      Computed tomography revealed an obstruction of the reconstructed portal vein and
      varices at the hepaticojejunostomy site. We diagnosed variceal bleeding and
      performed percutaneous transhepatic stenting in the obstructed portal vein. The
      patient was discharged in good clinical condition on day 15 after stenting. In
      conclusion, portal vein stenting is a useful and less invasive therapy for portal
      vein stenosis.

PMID- 30275752
TI  - High Levels of Serum Adipocyte Fatty Acid-binding Protein Predict Cardiovascular
      Events in Coronary Artery Disease Patients.
AB  - Background: Adipocyte fatty acid-binding protein (A-FABP) is a cardiometabolic
      predictor of cardiovascular (CV) disease in humans. We evaluated the association
      between serum A-FABP levels and future CV events in patients with coronary artery
      disease (CAD). Methods: A total of 106 CAD patients were enrolled in this study
      between January and December 2012 and were followed-up until June 30, 2017. The
      primary endpoint was the incidence of major adverse CV events. Results: During a
      median follow-up period of 53 months, 44 CV events occurred. Patients with CV
      events presented higher systolic blood pressure (p = 0.020), total serum
      cholesterol (p = 0.047), and serum A-FABP levels (p < 0.001) compared with
      patients without CV events. Kaplan-Meier analysis showed that the cumulative
      incidence of CV events in the high A-FABP group (median A-FABP concentration of
      >17.63 ng/mL) was higher than that in the low A-FABP group (log-rank p < 0.001).
      Multivariate Cox analysis showed that triglycerides (hazard ratio (HR): 1.008,
      95% confidence interval (CI): 1.001-1.016, p = 0.026) and serum A-FABP levels
      (HR: 1.027, 95% CI: 1.009-1.047, p = 0.004) were independently associated with CV
      events. Conclusion: Serum A-FABP level is a biomarker for future CV events in
      patients with CAD. Further prospective studies are needed to confirm the
      mechanisms underlying this association.

PMID- 30275751
TI  - A New Isolation Method of Human Lacrimal Canaliculus Epithelial Stem Cells by
      Maintaining Close Association with Their Niche Cells.
AB  - Purpose: To investigate whether lacrimal canaliculus epithelial stem cells
      (LCESC) could be isolated and expanded in vitro. Methods: The lacrimal
      canaliculus epithelium of 6 patients with limbal stem cell deficiency (LSCD)
      caused by alkali burn or Stevens Johnson Syndrome were examined by lacrimal
      endoscope. Cadaveric eyelids were fixed and prepared for cross section and
      stained with HE and antibodies against PCK, Vim, p63alpha, SCF and c-Kit.
      Canaliculus tissue was separated under an operating microscope using a lacrimal
      probe as an indicator and digested with collagenase A. The clusters of epithelial
      cells with closely associated stroma were further digested with Trypsin/EDTA to
      obtain single cells for culture on Matrigel-coated plastic plates in MESCM media.
      The expression of SCF, c-Kit and p63alpha was determined by immunostaining. The
      colony-forming efficiency on 3T3 feeder layers was also measured by calculating
      the percentage of the clone number divided by the total number cells seeded.
      Results: The epithelial layers of five out of six inferior lacrimal canaliculi
      and all the six superior lacrimal canaliculi were visually normal in appearance.
      Five to fifteen layers of the epithelium in the human lacrimal canaliculi were
      present with a small, tightly compacted basal layer of cells expressing PCK,
      p63alpha, SCF and c-Kit. LCESC were isolated by collagenase A and obtained clonal
      growth in MESCM. The colony-forming efficiency of LCESC holoclones on a 3T3
      feeder layer was 3.2%, compared to 1.9% for those of limbal stem cells (LSC).
      Conclusions: Herein, we first report that LCESCs can be isolated and have stem
      cell characteristics, similar to those of LSCs. Such a discovery raises a
      promising substrate resource of stem cells for LSC reconstruction in LSCD
      patients.

PMID- 30275753
TI  - Randomized, controlled clinical pilot study of venous leg ulcers treated with
      using two types of shockwave therapy.
AB  - Background. Venous leg ulcers are difficult to heal wounds. The basis of their
      physiotherapeutic treatment is compression therapy. However, for many years, the
      search for additional or other methods to supplement the treatment of venous
      ulcers, which would shorten the duration of treatment, is underway. One of such
      methods is the shockwave therapy. Methods. The purpose of our study was to
      compare radial shockwave therapy (R-ESWT) with focused shockwave therapy (F-ESWT)
      in venous leg ulcers treatment. Patients were randomly assigned to tree groups.
      In the first group the radial shockwave therapy (0.17mJ/mm2, 100 impulses/cm2, 5
      Hz), in the second group the focused shockwave therapy (0.173mJ/mm2, 100
      impulses/cm2, 5 Hz) was used and in third group standard care was used. Patients
      in shockwave therapy groups were given 6 treatments at five-day intervals. Total
      area, circumference, Gilman index, maximum length and maximum width of ulcers
      were measured. The patients from the third group wet gauze dressing with saline
      and gently compressing elastic bandages were used (standard wound care SWC).
      Results. Analysis of the results shows that a complete cure of ulcers was
      achieved in 35% of patients who were treated with radial shockwave, 26% of
      patients with focused shockwave used. There is statistically significant
      difference between the standard care and radial shockwave therapy as well as
      between the standard care and focused shockwave therapy. There is no
      statistically significant difference between the use of radial and focused
      shockwave in the treatment of venous leg ulcers (p> 0.05). Conclusion. There is
      no statistically significant difference between the use of radial and focused
      shockwave in the treatment of venous leg ulcers. Treatment of venous leg ulcers
      with shockwaves is more effective than the standard wound care.

PMID- 30275754
TI  - Cannabinoids: from pot to lab.
AB  - Cannabis is becoming increasingly present in our society. In recent years, the
      line between the natural (cannabis) and the synthetic (synthetic cannabinoids),
      the recreational (cannabis) and the medical (pharmaceutical cannabinoids and
      medical cannabis) has been crossed. In this paper we review some of the novel
      aspects of cannabis and cannabinoids in relation to their legal situation,
      changes in their composition and forms of cannabis use, the concept of medical
      cannabis, and synthetic cannabinoids as new psychoactive substances (NPS). We
      have also analyzed serious adverse reactions and intoxications associated with
      the use of synthetic cannabinoids, as well as the latest developments in the
      research of pharmaceutical cannabinoids.

PMID- 30275755
TI  - Eicosapentaenoic acid reduces indoleamine 2,3-dioxygenase 1 expression in tumor
      cells.
AB  - Marine plants and animals have omega-3 fatty acids including eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA). EPA is required for biological
      processes, but humans are unable to synthesize them and must be obtained from
      dietary sources. EPA has been used as an antitumor agent but the molecular
      mechanisms for the regulation of tumor microenvironment immunity by EPA are still
      unknown. The indoleamine 2,3-dioxygenase 1 (IDO) catalyzes conversion of
      tryptophan to kynurenine to induce immune evasion in tumor microenvironment. In
      this study, EPA inhibited the expression of IDO via downregulation of protein
      kinase B (Akt)/mammalian targets of rapamycin (mTOR) signaling pathway in tumor
      cells. Meanwhile, a significant decrease in kynurenine levels and increase in T
      cell survival were observed after tumor cells treated with EPA. The results
      demonstrated that EPA can activate host antitumor immunity by inhibiting tumor
      IDO expression. Therefore, our finding suggests that EPA can be enormous
      potential for cancer immunotherapy.

PMID- 30275756
TI  - The Role of YB1 in Renal Cell Carcinoma Cell Adhesion.
AB  - Background: Y-box binding protein 1 (YB1) is a multifunctional protein involved
      in many processes related to cancer progression and metastasis. Methods: In this
      study, we constructed YB1 knockdown stable renal cell carcinoma (RCC) cell line
      786-0. The gene expression profile of 786-0 was performed by DNA microarray
      analysis to identify genes that were regulated by YB1. Real-time PCR and western
      blotting were used to test the genes and proteins expression. Transforming growth
      factor-beta (TGF-beta) activity was detected by dual-luciferase reporter assay.
      Cell adhesion assay was used to determine RCC cell adhesion ability. Results:
      Pathway analysis revealed that YB1 knockdown influenced cell adhesion molecules
      (CAMs). We further verified four genes (CLDN4, NRXN3, ITGB8, and VCAN) related to
      CAMs by real-time PCR, and confirmed that YB1 regulated the expression of ITGB8
      in RCC. Functional assays demonstrated that knockdown of YB1 significantly
      inhibited the cell adhesion of 786-0 cells in vitro. In addition, YB1 affected
      TGF-beta activation. Conclusion: Our study demonstrated that YB1 modulated the
      adhesion ability of renal cell carcinoma cells by regulating ITGB8 and TGF-beta.

PMID- 30275757
TI  - Significant association of long non-coding RNAs HOTAIR genetic polymorphisms with
      cancer recurrence and patient survival in patients with uterine cervical cancer.
AB  - Up to date, no study explores the relationship of single nucleotide polymorphisms
      (SNPs) of long non-coding RNAs HOTAIR (lncRNAs HOTAIR) with cancer recurrence and
      patient survival in uterine cervical cancer for Taiwanese women. We therefore
      designed this study to investigate the clinical roles of lncRNAs HOTAIR SNPs in
      cervical cancer. One hundred and sixteen patients with cervical invasive cancer
      and 96 patients with preinvasive lesions as well as 318 control women were
      consecutively recruited. LncRNAs HOTAIR SNPs rs920778, rs12427129, rs4759314 and
      rs1899663 were analyzed and their genotypic frequencies were examined by real
      time polymerase chain reaction. The results indicated that there were no
      genotypic differences between patients with cervical neoplasia and normal
      controls as well as among patients with invasive and invasive cancer, and normal
      controls. However, genotype GG in lncRNAs HOTAIR SNP rs920778 was demonstrated to
      be a predictor for poorer cancer recurrence probability [p=0.001, hazard ratio
      (HR): 7.25, 95% CI: 2.19-23.96]. Furthermore, cervical cancer patients with
      genotype GG in lncRNAs HOTAIR rs920778 had worse overall survival (p =0.002, HR:
      7.22, 95% CI: 2.09-24.92). No significant associations exhibited between lncRNAs
      HOTAIR SNP rs920778 and clinicopathological parameters. In conclusion, this
      studied lncRNAs HOTAIR SNPs are not associated with cervical carcinongensis.
      However, lncRNAs HOTAIR SNP rs920778 may be regarded as an independent predictor
      of cancer recurrence probability and overall survival in cervical cancer
      patients.

PMID- 30275758
TI  - Estrogen Receptor 1 (ESR1) Enhances Slc2a4/GLUT4 Expression by a SP1 Cooperative
      Mechanism.
AB  - Background: Estrogens are involved in glycemic regulation, playing an important
      role in the development and/or progression of insulin resistance. For that,
      estrogens regulate the expression of the glucose transporter protein GLUT4
      (codified by the solute carrier family 2 member 4 gene, Slc2a4), thus modulating
      adipose and muscle glucose disposal. This regulation is a balance between ESR1
      mediated enhancer effect and ESR2-mediated repressor effect on Slc2a4 gene.
      However, molecular mechanisms involved in these effects are poorly understood.
      Since the specificity protein 1 (SP1) participates in several ESR-mediated
      genomic regulations, the aim of the present study is to investigate the
      participation of SP1 in the ESR1/2-mediated regulation of Slc2a4 gene. Methods:
      Differentiated 3T3-L1 adipocytes were 24-hour challenged with 10 nM estradiol
      (E2) and 10 nM ESR1 agonist (PPT) or 100 nM ESR2 agonist (DPN), added or not with
      E2. Slc2a4 and Sp1 mRNAs (RT-qPCR), total GLUT4 and nuclear ESR1, ESR2 and SP1
      proteins (Western blotting), SP1 binding activity into Slc2a4 promoter (EMSA),
      and nuclear complexation of SP1/ESR1 (immunoprecipitation) were analyzed.
      Results: E2 and PPT increased (25-50%) whereas DPN reduced (20-45%) Slc2a4 and
      GLUT4 expression. Nuclear content of ESR1 and ESR2 remained unchanged. Nuclear
      content of SP1 increased (50 to 90%) by PPT and DPN added or not with E2; the
      highest effect observed with PPT alone. PPT also increased the nuclear content of
      SP1/ESR1 complex and the SP1 binding into the Slc2a4 promoter. Conclusions: ESR1
      activation in adipocytes increased the nuclear content of SP1 protein, the
      SP1/ESR1 interaction and SP1 binding into the Slc2a4 gene promoter, culminating
      with increased Slc2a4/GLUT4 expression. No involvement of SP1 seems to occur in
      ESR2-mediated repressor effect on Slc2a4. We expect that this ESR1/SP1
      cooperative effect can contribute to the development of new approaches for
      prevention or treatment of insulin resistance and diabetes mellitus.

PMID- 30275759
TI  - Mitochondrial NADH Dehydrogenase Subunit 3 (MTND3) Polymorphisms are Associated
      with Gastric Cancer Susceptibility.
AB  - Accumulating evidence indicates that mitochondrial DNA alterations contribute to
      cancer development and progression. In this study, we evaluated the relationship
      between polymorphisms of mitochondrial NADH dehydrogenase subunit 3 (MTND3) and
      the risk of gastric cancer (GC). Five single nucleotide polymorphisms (SNPs;
      rs28358278, rs2853826, rs201397417, rs41467651, and rs28358275) were identified
      and genotyped in 377 patients with GC patients and 363 controls by direct
      sequencing. The rs41467651 T allele was significantly associated with GC risk
      [adjusted odds ratio (OR) = 2.11, 95% confidence interval (CI) = 1.25-3.55, P =
      0.005). In stratified analysis, rs28358278, rs2853826, and rs41467651 were
      associated with subgroups of GC, with the rs28358278 G, rs2853826 T, and
      rs41467651 T alleles associated with an increased GC risk in females (adjusted OR
      = 1.70, 95% CI = 1.08-2.69, P = 0.023; adjusted OR = 1.78, 95% CI = 1.11-2.85, P
      = 0.016; adjusted OR = 2.07, 95% CI = 1.04-4.12, P = 0.038, respectively). The
      rs441467651 T allele was also related with GC risk in diffuse-type subjects
      compared to that of controls (adjusted OR = 2.61, 95% CI = 1.43-4.89, P = 0.002).
      In addition, The rs441467651 T allele was significantly related with increased GC
      risk regardless of lymph node metastasis (LNM), T classification, and tumor stage
      compared to that of controls (adjusted OR = 2.00, 95% CI = 1.12-3.55, P = 0.019
      in LNM-negative subjects; adjusted OR = 2.10, 95% CI = 1.05-4.22, P = 0.0379 in
      LNM-positive subjects; adjusted OR = 1.82, 95% CI = 1.02-3.24, P = 0.042 in T1/T2
      subjects; adjusted OR = 2.60, 95% CI = 1.29-5.24, P = 0.007 in T3/T4 subjects;
      adjusted OR = 1.91, 95% CI = 1.09-3.34, P = 0.025 in tumor stage I (A+B)/II
      (A+B+C) subjects; adjusted OR = 2.36, 95% CI = 1.12-5.13, P = 0.025 in tumor
      stage III (A+B+C) subjects) compared to that of controls. Our findings suggest
      that the rs28358278, rs2853826, and rs41467651 polymorphisms of MTND3 increase
      the susceptibility to GC development.

PMID- 30275760
TI  - Impact of ADAM10 gene polymorphisms on hepatocellular carcinoma development and
      clinical characteristics.
AB  - A disintegrin and metalloprotease (ADAM) family proteins are type-I transmembrane
      glycoproteins with multiple functions in cell adhesion, migration, proteolysis
      and signaling. ADAM10 is a member of the ADAM family reportedly involved in
      cancer progression and has been shown to be overexpressed in hepatocellular
      carcinoma (HCC) tissues and significantly associated with tumor progression and
      shortened survival. This study investigated ADAM10's single nucleotide
      polymorphisms (SNPs) and their association to HCC development and regulation.
      Real-time polymerase chain reaction was used to analyze five SNPs of ADAM10 in
      333 patients with HCC and 1196 controls without cancer. The results indicated
      that of the 333 patients with HCC, those who carried ADAM10 rs514049 (AC + CC)
      variants had a higher risk of developing lymph node metastasis (odds ratio [OR] =
      5.087, p = 0.027), and those who carried ADAM10 rs653765 (GA + AA) variants had a
      higher risk of developing distant metastasis (OR = 3.346, p = 0.020) and higher
      levels of alpha-fetoprotein. In conclusion, our study demonstrated that the SNPs
      of ADAM10 are involved in HCC progression. ADAM10 SNPs may be used as therapeutic
      targets to evaluate poor prognoses for HCC.

PMID- 30275761
TI  - Thrombopoietin could protect cerebral tissue against ischemia-reperfusion injury
      by suppressing NF-kappaB and MMP-9 expression in rats.
AB  - Objective: To determine the neuroprotective effects and underpinning mechanisms
      of thrombopoietin (TPO), Matrix Metalloproteinase-9(MMP-9) and Nuclear Factor
      kappaB (NF-kappaB) after focal cerebral ischemia-reperfusion in rats. Methods:
      Male rats underwent 2 hours of right middle cerebral artery occlusion (MCAO)
      followed by 22 hours of reperfusion. PBS or TPO (0.1ug/kg) was administered from
      caudal vein before reperfusion. Neurologic deficits, brain edema, Evans blue (EB)
      extravasation, NF-kappaB and MMP-9 expression were subsequently examined.
      Results: Ischemia-reperfusion injury produced a large area of edema. TPO
      significantly reduced edema and alleviated neurologic deficits after ischemia
      reperfusion. Ischemia-induced increases of NF-kappaB, MMP-9 and Evans blue
      extravasation were reduced by TPO intervention. Conclusion: TPO improved
      neurological function and ameliorated brain edema after stroke, partly by
      reducing the ischemia-induced increase of NF-kappaB and MMP-9.

PMID- 30275762
TI  - GABAergic Alterations in the Rat Testis after Methamphetamine Exposure.
AB  - Gamma-aminobutyric acid (GABA), GABA-A receptors and GABA transporter 1 (GAT1)
      were reported to be involved in the proliferation of Leydig cells, testosterone
      production and spermatogenesis. Since methamphetamine (METH) has been reported to
      have adverse effects on testis and its functions, the aim of this study was
      therefore to determine the changes of GABAergic activity in testis after METH
      exposure. Male Sprague-Dawley rats were divided into control, acute binge (AB
      METH), escalating dose (ED METH) and escalating dose-binge (ED-binge METH)
      groups. After sacrifice, rat testes were removed and used to estimate GABA
      concentration and the expression of GABA-A receptor, GAD1, GAD2 and GAT1 genes by
      using HPLC and RT-PCR, respectively. The GABA concentration was significantly
      increased in all METH-administrated groups. In addition, significant increases of
      GABA-A alpha1 receptor and GAD1 genes expression were found in the ED-binge METH
      group. Gene expressions of GAT1 were numerically decreased in all METH
      administrated rats and reached significant in the ED METH group. These results
      indicated a compensatory upregulation of GABA production and its functions in
      testis after METH exposure. Thus, these changes might represent a homeostatic
      response of GABAergic to the adverse effects of METH.

PMID- 30275763
TI  - Erratum: Association of Genes Variants in RANKL/RANK/OPG Signaling Pathway with
      the Development of Osteonecrosis of the Femoral Head in Chinese Population:
      Erratum.
AB  - [This corrects the article DOI: 10.7150/ijms.19124.].

PMID- 30275764
TI  - AGK2, A SIRT2 Inhibitor, Inhibits Hepatitis B Virus Replication In Vitro And In
      Vivo.
AB  - Sirtuin 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD +)-dependent class
      III histone deacetylase. We have reported that HBx (hepatitis B virus X protein)
      elevated SIRT2 promotes HBV replication and hepatocarcinogenesis. However, the
      potential anti-HBV effect of AGK2, a selective inhibitor of SIRT2, has not been
      reported. Here, the role of AGK2 on HBV replication was examined in the HepAD38
      and HepG2-NTCP cell lines. The HBV genome was stably integrated in HepAD38 cell
      line which expresses HBV under the control of tetracycline. The HepG2-NTCP cells
      expressing the sodium taurocholate cotransporting polypeptide (NTCP) receptor are
      susceptible to HBV infection. We found that AGK2 exhibited a robust anti-HBV
      activity with minimal hepatotoxicity. AGK2 inhibited the expression of HBV total
      and 3.5kb RNAs, DNA replicative intermediates and HBV core protein (HBc).
      Moreover, AGK2 treatment suppressed the secretion of the hepatitis B e antigen
      (HBeAg) and hepatitis B surface antigen (HBsAg). Importantly, AGK2 treatment
      inhibited serum HBV DNA, HBeAg and HBsAg levels as well as hepatic HBV DNA, RNA
      and HBc in the HBV transgenic mice. The results indicated that AGK2, as a SIRT2
      inhibitor, might be a new therapeutic option for controlling HBV infection.

PMID- 30275765
TI  - Acid-electrolyzed functional water induces extracellular matrix metalloproteinase
      inducer, a possible novel alarmin, secretion from oral squamous cell carcinoma
      cell lines.
AB  - Extracellular matrix metalloproteinase inducer (EMMPRIN) secretion was induced in
      the oral squamous cell carcinoma cell line HSC3 cell by acid-electrolyzed
      functional water (FW) stimulation. Augmented EMMPRIN secretion was not under
      transcriptional control; rather, it was derived from the intracellular storages.
      EMMPRIN secretion was also induced under oxidative stress and accompanied by the
      release of lactate dehydrogenase (LDH). The molecules released from cells
      undergoing necrosis are called as alarmins, and the secretion of IL-1alpha, a
      typical alarmin, was induced by FW stimulation and oxidative stress.
      Intracellular localization was examined by cell fractionation. A significant
      amount of EMMPRIN was localized in the triton X-100 and DNase sensitive
      fractions; the levels were drastically reduced following FW treatment. The
      function of the released EMMPRIN was examined using the monocytic cell line THP1.
      Culture supernatant derived from FW-treated HSC3 cells induced the expression of
      matrix metalloproteinases (MMPs) 1, 2, 8, 9, 13, and 14, platelet-derived growth
      factor, and interleukin-8. In contrast, vascular endothelial growth factor
      expression was reduced. Induction of these factors was abolished following
      eliminating of EMMPRIN by immunoprecipitation. These results indicate that
      EMMPRIN might be considered as a type of alarmin that transduces danger signals
      to the surrounding cells.

PMID- 30275766
TI  - The Relationship between Follicle-stimulating Hormone and Bone Health:
      Alternative Explanation for Bone Loss beyond Oestrogen?
AB  - Bone loss in women commences before the onset of menopause and oestrogen
      deficiency. The increase of follicle-stimulating hormone (FSH) precedes oestrogen
      decline and may be a cause for bone loss before menopause. This review summarizes
      the current evidence on the relationship between FSH and bone derived from
      cellular, animal and human studies. Cellular studies found that FSH receptor
      (FSHR) was present on osteoclasts, osteoclast precursors and mesenchymal stem
      cells but not osteoblasts. FSH promoted osteoclast differentiation, activity and
      survival but exerted negligible effects on osteoblasts. Transgenic FSHR or FSH
      knockout rodents showed heterogenous skeletal phenotypes. Supplementation of FSH
      enhanced bone deterioration and blocking of FSH action protected bone of rodents.
      Human epidemiological studies revealed a negative relationship between FSH and
      bone health in perimenopausal women and elderly men but the association was
      attenuated in postmenopausal women. In conclusion, FSH may have a direct action
      on bone health independent of oestrogen by enhancing bone resorption. Its effects
      may be attenuated in the presence of overt sex hormone deficiency. More
      longitudinal studies pertaining to the effects of FSH on bone health, especially
      on fracture risk, should be conducted to validate this speculation.

PMID- 30275767
TI  - B355252, A Novel Small Molecule, Confers Neuroprotection Against Cobalt Chloride
      Toxicity In Mouse Hippocampal Cells Through Altering Mitochondrial Dynamics And
      Limiting Autophagy Induction.
AB  - Cerebral hypoxia as often occurs in cases of stroke, hemorrhage, or other
      traumatic brain injuries, is one of the leading causes of death worldwide and a
      main driver of disabilities in the elderly. Using a chemical mimetic of hypoxia,
      cobalt chloride (CoCl2), we tested the ability of a novel small molecule, 4
      chloro-N-(naphthalen-1-ylmethyl)-5-(3-(piperazin-1-yl)phenoxy)thiophene-2
      sulfonamide (B355252), to alleviate CoCl2-induced damage in mouse hippocampal
      HT22 cells. A dose-dependent decrease in cell viability was observed during CoCl2
      treatment along with increases in mitochondrial membrane potential and generation
      of reactive oxygen species (ROS). B355252 conferred protection against these
      changes. We further found that mitochondrial dynamics, the balance between
      mitochondrial fusion and fission, were perturbed by CoCl2 treatment.
      Mitochondrial fusion, which was assessed by measuring the expression of proteins
      optic atrophy protein 1 (OPA1) and mitofusin 2 (Mfn2), declined due to CoCl2
      exposure, but B355252 addition was able to elevate Mfn2 expression while OPA1
      expression was unchanged. Mitochondrial fission, measured by phosphorylated
      dynamin-related protein 1 (p-DRP1) and fission protein 1 (FIS1) expression, also
      decreased following CoCl2 exposure, and was stabilized by B355252 addition.
      Finally, autophagy was assessed by measuring the conversion of cytosolic
      microtubule-associated protein 1A/1B-light chain three-I (LC3-I) to autophagosome
      bound microtubule-associated protein 1A/1B-light chain three-II (LC3-II) and was
      found to be increased by CoCl2. B355252 addition significantly reduced autophagy
      induction. Taken together, our results indicate B355252 has therapeutic potential
      to reduce the damaging effects caused by CoCl2 and should be further evaluated
      for applications in cerebral ischemia therapy.

PMID- 30275768
TI  - The Emperor's New Clothes: a Critical Appraisal of Evidence-based Medicine.
AB  - Evidence-Based Medicine (EBM) is the way we are expected to deliver our
      healthcare in the 21st century. It has been described as the integration of
      information from best available evidence with the doctor's experience and the
      patient's point of view. Unfortunately, the original meaning of EBM has been lost
      and the worldwide medical community has shifted the paradigm to Guidelines-Based
      Medicine, that has displaced the figures of the doctor and the patient from the
      decision-making process and relegated them to mere executor and final target of
      decisions taken by someone else. Problems related to the reliability of evidence
      and to the way guidelines are constructed, implemented and followed are discussed
      in detail. It is mandatory that the whole medical community takes responsibility
      and tries to reverse this apparently inexorable process so to re-establish a
      proper evidence-based care, where patients and their healing relation with
      practitioners are at the centre and where doctors are able to critically evaluate
      the available evidence and use it in light of their personal experience and
      knowledge.

PMID- 30275769
TI  - Characterization and potential roles of bone marrow-derived stromal cells in
      cancer development and metastasis.
AB  - Background: The tumor microenvironment and its stromal cells play an important
      role in cancer development and metastasis. Bone marrow-derived cells (BMDCs), a
      rich source of hematopoietic and mesenchymal stem cells, putatively contribute to
      this tumoral stroma. However their characteristics and roles within the tumor
      microenvironment are unclear. In the present study, BMDCs in the tumor
      microenvironment were traced using the green fluorescent protein (GFP) bone
      marrow transplantation model. Methods: C57BL/6 mice were irradiated and rescued
      by bone marrow transplantation from GFP-transgenic mice. Lewis lung cancer cells
      were inoculated into the mice to generate subcutaneous allograft tumors or lung
      metastases. Confocal microscopy, immunohistochemistry for GFP, alpha-SMA, CD11b,
      CD31, CD34 and CD105, and double-fluorescent immunohistochemistry for GFP-CD11b,
      GFP-CD105 and GFP-CD31 were performed. Results: Round and dendritic-shaped GFP
      positive mononuclear cells constituted a significant stromal subpopulation in
      primary tumor peripheral area (PA) and metastatic tumor area (MA)
      microenvironment, thus implicating an invasive and metastatic role for these
      cells. CD11b co-expression in GFP-positive cells suggests that round/dendritic
      cell subpopulations are possibly BM-derived macrophages. Identification of GFP
      positive mononuclear infiltrates co-expressing CD31 suggests that these cells
      might be BM-derived angioblasts, whereas their non-reactivity for CD34, CD105 and
      alpha-SMA implies an altered vascular phenotype distinct from endothelial cells.
      Significant upregulation of GFP-positive, CD31-positive and GFP/CD31 double
      positive cell densities positively correlated with PA and MA (P<0.05).
      Conclusion: Taken together, in vivo evidence of traceable GFP-positive BMDCs in
      primary and metastatic tumor microenvironment suggests that recruited BMDCs might
      partake in cancer invasion and metastasis, possess multilineage potency and
      promote angiogenesis.

PMID- 30275771
TI  - The experimental study of shunt-decompression arterialized vein flap.
AB  - Background: Arterialized vein flap is a kind of unphysiological flap.
      Unphysiological reconstruction of blood circulation leads to higher load than
      that supported by physiological flap and is the culprit of flap swelling, blood
      stasis, skin blistering, and necrosis after flap grafting. To resolve the
      multiple disadvantages of traditional flap grafting, by introducing the
      principles of fluid mechanics, shunt-decompression surgery is prepared to decline
      the circulation preload and improve the prognosis of arterialized vein flap
      grafting. Methods: By introducing the principles of fluid mechanics, we
      established the model of shunt-decompression arterialized vein flap, which
      satisfied the common properties of general fluid that the interface pressure
      between object and fluid is reduced when the velocity of fluid is increased and
      vice versa-the effect of Bernoulli. Under this rule, we anastomose the
      arterialized vein to the branch of main artery of recipient region or make end-to
      side anastomosis, which can maintain the blood flow of main artery, decrease the
      perfusion of flap, and preserve the decompressive effect of main artery to
      branches. From March, 2016 to September, 2016, we performed animal experiments on
      ten male bama mini pigs with average weight of 28 +/- 2.35 kg. Superior
      epigastric artery of pig was used for feeding artery to arterialize the
      superficial epigastric veins. The total area of flap is 8 cm * 6 cm. End-to-side
      anastomosis and end-to-end anastomosis were established in experimental group and
      control group, respectively. Doppler speckle perfusion imaging apparatus was used
      to monitor the alterations of flap perfusion, blood flow of flap, tissue swelling
      and survival of flaps. Results: The average flap perfusion (PU) at 1 week after
      surgery is 83.62 +/- 3.14 in experimental group and 98.14 +/- 6.54 in control
      group, respectively (P < 0.05), indicating the significant reduction of flap
      blood perfusion in experimental group as compared with control group. As to the
      survival of flaps, 7 flaps completely survived, 3 showed partial necrosis, and no
      one was found as complete necrosis in experimental group, while only 3 flaps
      survived, and 4 flaps and 3 flaps showed partial necrosis and complete necrosis
      in control group, respectively (P < 0.05). Conclusion: Based on the physiological
      features of arterialized vein flap and its problems in clinical application, we
      improved the anastomosis strategy of flap grafting and obtained excellent
      experimental outcomes, which provides an insight for the clinical application of
      arterialized vein flaps.

PMID- 30275770
TI  - Role of TCF/LEF Transcription Factors in Bone Development and Osteogenesis.
AB  - Bone formation occurs by two distinct mechanisms, namely, periosteal ossification
      and endochondral ossification. In both mechanisms, osteoblasts play an important
      role in the secretion and mineralization of bone-specific extracellular matrix.
      Differentiation and maturation of osteoblasts is a prerequisite to bone formation
      and is regulated by many factors. Recent experiments have shown that
      transcription factors play an important role in regulating osteoblast
      differentiation, proliferation, and function. Osteogenesis related transcription
      factors are the central targets and key mediators of the function of growth
      factors, such as cytokines. Transcription factors play a key role in the
      transformation of mesenchymal progenitor cells into functional osteoblasts. These
      transcription factors are closely linked with each other and in conjunction with
      bone-related signaling pathways form a complex network that regulates osteoblast
      differentiation and bone formation. In this paper, we discuss the structure of T
      cell factor/lymphoid enhancer factor (TCF/LEF) and its role in embryonic skeletal
      development and the crosstalk with related signaling pathways and factors.

PMID- 30275772
TI  - Marsdenia tenacissima extract induces apoptosis and suppresses autophagy through
      ERK activation in lung cancer cells.
AB  - Background: Marsdenia tenacissima is an herb medicine which has been utilized to
      treat malignant diseases for decades. The M. tenacissima extract (MTE) shows
      significant anti-proliferation activity against non-small cell lung cancer
      (NSCLC) cells, but the underlying mechanisms remain unclear. In this study, we
      explored the potential anti-proliferation mechanisms of MTE in NSCLC cells in
      relation to apoptosis as well as autophagy, which are two critical forms to
      control cancer cell survival and death. Methods: The proliferation of H1975 and
      A549 cells was evaluated by MTT assay. Cell apoptosis was assessed by Annexin V
      and PI staining, Caspase 3 expression and activity. Autophagy flux proteins were
      detected by Western blot with or without autophagy inducer and inhibitor.
      Endogenous LC3-II puncta and LysoTracker staining were monitored by confocal
      microscopy. The formation of autophagic vacuoles was measured by acridine orange
      staining. ERK is a crucial molecule to interplay with cell autophagy and
      apoptosis. The role of ERK on cell apoptosis and autophagy influenced by MTE was
      determined in the presence of MEK/ERK inhibitor U0126. Results: The significant
      growth inhibition and apoptosis induction were observed in MTE treated NSCLC
      cells. MTE induced cell apoptosis coexisted with elevated Caspase 3 activity. MTE
      also impaired autophagic flux by upregulated LC3-II and p62 expression. Autophagy
      inducer EBSS could not abolish the impaired autophagic flux by MTE, while it was
      augmented in the presence of autophagy inhibitor Baf A1. The autophagosome
      lysosome fusion was blocked by MTE via affecting lysosome function as evidenced
      by decreased expression of LAMP1 and Cathepsin B. The molecule ERK became
      hyperactivated after MTE treatment, but the MEK/ERK inhibitor U0126 abrogated
      autophagy inhibition and apoptosis induction caused by MTE, suggested that ERK
      signaling pathways partially contributed to cell death caused by MTE. Conclusion:
      Our results demonstrate that MTE caused apoptosis induction as well as autophagy
      inhibition in NSCLC cells. The activated ERK is partially associated with NSCLC
      apoptotic and autophagic cell death in response to MTE treatment. The present
      findings reveal new mechanisms for the anti-tumor activity of MTE against NSCLC.

PMID- 30275775
TI  - A Tribute to John L. Ochsner, Sr., MD.

PMID- 30275773
TI  - Circulating activated protein C levels are not increased in septic patients
      treated with recombinant human soluble thrombomodulin.
AB  - Background: Recombinant human soluble thrombomodulin (rTM) has been used for the
      treatment of disseminated intravascular coagulation in Japan, and an
      international phase III clinical trial for rTM is currently in progress. rTM
      mainly exerts its anticoagulant effects through an activated protein C (APC)
      dependent mechanism, but the circulating APC levels after rTM treatment have not
      been clarified. This prospective observational study investigated plasma APC
      levels after rTM treatment. Methods: Plasma levels of soluble thrombomodulin,
      thrombin-antithrombin complex (TAT), protein C, and APC were measured in eight
      septic patients treated with rTM. APC generation in vitro was assessed in the
      presence or absence of rTM. Results: rTM significantly increased thrombin
      mediated APC generation in vitro. In septic patients, soluble thrombomodulin
      levels were significantly increased during a 30-60-min period of rTM treatment
      and TAT levels were decreased. However, APC activity was not increased during the
      treatment period. Conclusions: Plasma APC activity is not increased in septic
      patients treated with rTM. It is possible that APC acts locally and does not
      circulate systemically.

PMID- 30275774
TI  - A New ELISA to Overcome the Pitfalls in Quantification of Recombinant Human
      Monoclonal Anti-HBs, GC1102, by Commercial Immunoassays.
AB  - Several methods for the quantification of human anti-HBs, an antibody to
      hepatitis B surface antigen (HBsAg), have been developed based on enzyme
      reaction, chemiluminescence, fluorescence, and radioactivity for application to
      human serum or plasma. Commercial anti-HBs immunoassay kits use a sandwich method
      in which a bridge is formed by the anti-HBs between a HBsAg immobilized solid
      matrix and the labeled HBsAg. However, this direct sandwich enzyme-linked
      immunosorbent assay (ELISA) is insufficient to accurately evaluate the activity
      of the human monoclonal anti-HBs, GC1102. As an alternative, we developed an
      indirect anti-HBs ELISA (anti-HBs qELISA_v.1) that improved detection of anti
      HBs. In this current study, we further optimized this indirect method to minimize
      nonspecific binding of human serum, by employing incubation buffers containing
      animal serum, Tween 20, skim milk, and a low pH washing buffer. This new and
      improved method, termed anti-HBs qELISA_v.2, showed accurate quantification of
      plasma-derived hepatitis B immune globulin (HBIG) and was comparable to results
      obtained with commercial ELISA (r = 0.93) and RIA (r = 0.85) kits. Further, the
      GC1102 in human serum could be precisely measured using the anti-HBs qELISA_v.2
      without limitations of nonspecific binding.

PMID- 30275776
TI  - Utilization of LCP-Tacrolimus (Envarsus XR) in Simultaneous Pancreas and Kidney
      Transplant Recipients.

PMID- 30275778
TI  - Spiritual Awareness in the Healthcare Workplace.

PMID- 30275777
TI  - Antithrombotic Therapy After Percutaneous Left Atrial Appendage Occlusion Using
      the WATCHMAN Device.

PMID- 30275779
TI  - Ethical Implications of Clinical Genomic Information, Records Research, and
      Informed Consent.

PMID- 30275780
TI  - Compassion: Lessons from the Humanities.

PMID- 30275781
TI  - Feasibility of REBOA-Resuscitative Endovascular Balloon Occlusion of the Aorta-in
      Trauma-Related Noncompressible Torso Hemorrhage at Two Metropolitan Trauma
      Centers.

PMID- 30275782
TI  - Predicting American Board of Emergency Medicine Qualifying Examination Passage
      Using United States Medical Licensing Examination Step Scores.
AB  - Background: The objective of the current study was to determine whether emergency
      medicine residents' United States Medical Licensing Examination (USMLE) scores
      are significantly associated with first-attempt passage of the American Board of
      Emergency Medicine (ABEM) qualifying (written) examination. We hypothesized that
      USMLE Step 2 Clinical Knowledge (CK) scores would be useful in predicting
      students who passed the ABEM qualifying examination on their first attempt.
      Methods: For this retrospective cohort study, we examined the data of residents
      who successfully completed training at two emergency medicine residency programs
      between the years 2002-2013. Because scores on the USMLE Step examinations varied
      greatly across years, we obtained means and standard deviations from the National
      Board of Medical Examiners. We subtracted the mean score for the year each
      resident took the examination from the resident's examination score, creating
      centered Step 1 and centered Step 2 CK scores. Results: A multivariate logistic
      regression analysis indicated that centered Step 2 CK scores could be used to
      predict the odds of passing the ABEM qualifying examination (odds ratio = 1.05
      [95% confidence interval 1.02 to 1.08, P < 0.001]). Using a Step 2 CK score
      cutoff of 7 points lower than the mean yielded 64% sensitivity and 81%
      specificity for predicting passage of the ABEM written examination on the first
      attempt. Conclusion: Program directors and selection committees may wish to
      consider whether applicants' Step 2 CK scores are near the national average when
      making ranking decisions, as this variable is highly predictive of passing the
      ABEM qualifying examination on the initial attempt.

PMID- 30275783
TI  - Treatment of Occipital Neuralgia by Thermal Radiofrequency Ablation.
AB  - Background: Occipital neuralgia is an uncommon disorder characterized by severe
      pain involving the posterior scalp in the distribution of the greater and lesser
      occipital nerves. In cases refractory to pharmacotherapy, invasive treatment
      options may be warranted. The aim of the present study was to examine the effects
      of thermal radiofrequency ablation (TRF) on occipital neuralgia. We hypothesized
      that this procedure would result in long-term pain relief. Methods: All patients
      who underwent TRF of the greater and lesser occipital nerves between January 1,
      2013 and March 23, 2016 were identified. Medical records were reviewed for
      preprocedure pain score, 1-month postprocedure pain score, patient-defined
      percent pain relief according to the visual analog scale (on which zero equals no
      pain and 10 represents the worst pain imaginable), and length of pain relief. The
      primary outcomes were the differences between preprocedure and 1-month
      postprocedure pain scores (mean change from baseline), percent pain relief, and
      patient-reported length of relief. Results: A total of 50 patients were
      identified; 4 patients were excluded because of insufficient data as a result of
      loss to follow-up. A significant difference was found between preprocedure and
      postprocedure patient-reported pain scores (6.7 vs 2.7, respectively; P < 0.001),
      equating to a mean reduction in pain scores 1-month postprocedure of 4.0 +/- 3.3.
      The mean patient-defined percent pain relief was 76.3% +/- 25.0%. The mean
      patient-reported length of relief was 6.5 +/- 5.1 months. Conclusion: This study
      suggests that TRF may reduce pain scores for approximately 6 months.

PMID- 30275784
TI  - Rhabdomyolysis: Patterns, Circumstances, and Outcomes of Patients Presenting to
      the Emergency Department.
AB  - Background: Exertional rhabdomyolysis is a condition resulting from skeletal
      muscle damage and release of intracellular toxins into the systemic circulation
      as a consequence of extreme physical effort. With increasing numbers of people
      partaking in high-intensity workouts, we hypothesized that the rate of
      presentation of exertional rhabdomyolysis was also increasing. Methods: All
      presentations to the Princess Alexandra Hospital emergency department in
      Brisbane, Australia between March 2005 and December 2016 were identified from the
      electronic medical record. Records of patients with a serum creatine kinase value
      >1,000 U/L or a urinary myoglobin >5 mg/L were extracted for determination of
      whether the rhabdomyolysis was attributable to physical exertion. Results: From a
      total of 1,957 rhabdomyolysis cases, 89 patients (70.8% male) were identified as
      having exertional rhabdomyolysis. The frequency of presentation increased from
      0.28/10,000 presentations in 2005 to 3.5/10,000 in 2015. Gym-induced exertional
      rhabdomyolysis was the primary subcategory (53.9%) for these cases, and manual
      labor was the second most common subcategory (15.7%). Conclusion: This study
      provides evidence for increasing instances of exertional rhabdomyolysis in the
      Brisbane, Australia metropolitan area and adds to the current knowledge about
      those who develop exertional rhabdomyolysis. Future studies are warranted to
      investigate if similar trends are being seen in other regions and to identify the
      circumstances leading to the presentation. Such knowledge would be valuable for
      devising strategies to prevent and mitigate injury.

PMID- 30275785
TI  - Successful Treatment of Cesarean Scar Pregnancy With Suction Curettage: Our
      Experiences in Early Pregnancy.
AB  - Background: Cesarean scar pregnancy is an ectopic pregnancy embedded in the
      myometrium of a cesarean scar. Several types of conservative treatment have been
      used to treat cesarean scar pregnancy, but no management protocol has been
      established for this rare, life-threatening condition. The purpose of this study
      was to evaluate the feasibility of suction curettage as a first-line treatment in
      early cesarean scar pregnancy. Methods: During a 4-year period, 19 cases of
      cesarean scar pregnancy were diagnosed at Suleymaniye Maternity Hospital in
      Istanbul, Turkey. Suction curettage and Foley balloon tamponade were performed as
      a first-line treatment in 13 patients. Medical records and treatment results of
      the patients were evaluated. Results: The mean maternal age was 32.5 years
      (range, 24-39 years). The mean gestational sac diameter was 13.65 mm (range, 7.6
      27 mm), and mean endometrial thickness was 10.7 mm (range, 6.7-14.6 mm). A
      measurable fetal pole for crown-rump length was available for 6 (46.1%) patients.
      None of the fetuses had cardiac activity. Suction curettage under ultrasound
      guidance and Foley balloon tamponade were successful as the primary treatment in
      13 of 13 patients. No major complications occurred during or after the procedure.
      Conclusion: Our data suggest that surgical evacuation under ultrasound guidance
      with Foley balloon tamponade is a safe and successful treatment modality in
      carefully selected patients with early cesarean scar pregnancy.

PMID- 30275786
TI  - Effect of Obesity on Component Alignment in Total Knee Arthroplasty.
AB  - Background: Obesity is routinely cited as a negative predictive factor for
      outcomes after total knee arthroplasty (TKA), but the direct mechanism
      responsible for this relationship has not been described. One possible
      explanation is a propensity for component malalignment in obese patients that is
      attributable to difficulty with surgical exposure. Methods: This study evaluated
      the effect of obesity on TKA component alignment in 251 primary TKAs during a 12
      month period at a single center in 2009. Postoperative component alignment was
      retrospectively measured and compared between patients defined as obese (body
      mass index [BMI] >=30 kg/m2) and patients defined as nonobese (BMI <30 kg/m2).
      Alignment was determined by measuring the coronal tibiofemoral angle, coronal
      femoral component angle, coronal tibial component angle, sagittal femoral
      component angle, and sagittal tibial component angle in all of the study
      patients. Results: Statistical analysis failed to demonstrate a statistically
      significant relationship between obesity and component alignment in any of the
      measured parameters. Conclusion: The results of this study support that obesity
      does not negatively affect TKA component alignment; another factor must be
      associated with the worse outcomes in obese patients undergoing TKA.

PMID- 30275787
TI  - Hyponatremia in Association With Second-Generation Antipsychotics: A Systematic
      Review of Case Reports.
AB  - Background: Hyponatremia is generally defined as a serum sodium level <135 mmol/L
      and is considered severe if serum sodium is <125 mmol/L. Hyponatremia is a
      potentially life-threatening medical comorbidity for patients with schizophrenia.
      The incidence of hyponatremia in patients with schizophrenia who are taking
      second-generation antipsychotics (SGAs) has not been well established. Methods:
      We conducted a systematic review of case reports of hyponatremia associated with
      the use of SGAs in patients with schizophrenia. We searched MEDLINE (from 1946
      through September 2016) using the medical subject headings antipsychotic agents,
      hyponatremia, and water intoxication to identify reported diagnoses of
      hyponatremia following treatment with SGAs in patients with schizophrenia.
      Results: We abstracted 12 potentially relevant case reports from 157 records.
      Nine case reports met the selection criteria. Three cases involved the use of
      aripiprazole (Abilify), 3 involved the use of risperidone (Risperdal), and the
      other 3 cases involved ziprasidone, olanzapine, and clozapine. Approximately
      equal numbers of males and females were represented, and 2 of the 9 patients were
      aged >=60 years. The average patient age was 47 years, and the average time to
      the hyponatremia event was 17 days. The average serum sodium was 138 mmol/L at
      baseline, 112 mmol/L at treatment nadir, and 138 mmol/L after treatment
      discontinuation. Conclusion: Hyponatremia can result from the use of SGAs in
      patients with schizophrenia and can be avoided with proper management of
      treatment. Physicians, psychiatrists, and other healthcare workers should be
      aware of the potential for severe hyponatremia with the use of commonly
      prescribed SGAs. SGA-induced hyponatremia is generally reversible after
      discontinuing treatment.

PMID- 30275788
TI  - Advances in Neuro-Oncology Imaging Techniques.
AB  - Background: Central nervous system (CNS) tumors are a rare but devastating
      malignancy, often robbing patients of the basic quality of life. Despite advances
      in our understanding of the CNS tumor disease processes, the prognosis for
      patients with CNS tumors remains poor. Better characterization and diagnostic and
      monitoring approaches are necessary to assist in diagnosis and treatment of CNS
      tumors. One important tool in the neuro-oncology armamentarium is the use of
      advanced imaging techniques. Methods: We searched PubMed using the keywords neuro
      oncology imaging, pseudoprogression, molecular imaging, and biomarkers. We
      limited our search to full-text English articles and identified other relevant
      articles from the reference lists of previously identified articles. Results:
      Advances in imaging techniques have allowed investigators to explore various
      imaging modalities, from tumor characterization to differentiating
      pseudoprogression from tumor progression. Better imaging can result in better
      diagnostic approaches, greater and safer resection techniques, and improved
      monitoring of tumor progression. Conclusion: This review highlights advances in
      neuro-oncology imaging techniques and their clinical utility in the treatment and
      management of primary brain tumors.

PMID- 30275789
TI  - Dislocation of the Hip: A Review of Types, Causes, and Treatment.
AB  - Background: Dislocation of the hip is a well-described event that occurs in
      conjunction with high-energy trauma or postoperatively after total hip
      replacement. Methods: In this review, the types, causes, and treatment modalities
      of hip dislocation are discussed and illustrated, with particular emphasis on the
      assessment, treatment, and complications of dislocations following total hip
      replacement. Results: Hip dislocations are commonly classified according to the
      direction of dislocation of the femoral head, either anterior or posterior, and
      are treated with specific techniques for reduction. Generally, closed reduction
      is the initial treatment method, usually occurring in the emergency room. Bigelow
      first described closed treatment of a dislocated hip in 1870, and since then many
      reduction techniques have been proposed. Each method has unique advantages and
      disadvantages. Anterior hip dislocation is commonly reduced by inline traction
      and external rotation, with an assistant pushing on the femoral head or pulling
      the femur laterally to assist reduction. Posterior hip dislocations are the most
      common type and are reduced by placing longitudinal traction with internal
      rotation on the hip. Conclusion: Patients with hip dislocations must receive
      careful diagnostic workup, and the treating physician must be well versed in the
      different ways to treat the injury and possible complications. Timely evaluation
      and treatment, including recognizing the potential complications, are necessary
      to offer the best outcome for the patient.

PMID- 30275790
TI  - Role of Complementary and Alternative Medicine in Otolaryngologic Perioperative
      Care.
AB  - Background: During the perioperative period for otolaryngologic surgical cases,
      complications and delays can occur as the result of anxiety, pain, nausea, and
      vomiting. Conventional methods used to treat these symptoms include medications
      that can be expensive and invasive or that can cause adverse effects. Because of
      the concerns about opioid use in the United States, providers might want to
      consider using complementary and alternative medicine (CAM) as adjunctive or
      primary treatment plans. Methods: To assess the current knowledge about the
      clinical effectiveness of CAM for patients undergoing otolaryngologic procedures,
      we searched the literature using MEDLINE, PubMed, and Google Scholar. We excluded
      studies published prior to 1990 and articles about surgeries that were unrelated
      to otolaryngology. Results: An analysis of the selected studies revealed that CAM
      therapies-acupuncture, aromatherapy, hypnosis, and music therapy-have been shown
      to be effective at reducing preoperative anxiety, postoperative pain, and
      postoperative nausea and vomiting. No adverse side effects were associated with
      CAM use in these studies. Conclusion: The use of CAM in patients undergoing
      otolaryngologic surgeries may relieve common perioperative symptoms. While
      further study is warranted, otolaryngology providers might consider implementing
      CAM with patients electing surgery.

PMID- 30275791
TI  - Non-Human Leukocyte Antigen Antibody-Mediated Lung Transplant Rejection: The
      Other Anti-A.
AB  - Background: Acute rejection of lung allografts is an important contributor to
      morbidity and mortality in the transplant patient population, resulting in the
      dysfunction and destruction of the graft by the host's immune system via cellular
      or antibody-mediated mechanisms. Acute cellular rejection (ACR) is more common
      and better characterized than antibody-mediated rejection, which to date lacks
      any widely agreed upon, standardized set of diagnostic criteria. We present a
      case of AMR attributable to a rare phenomenon, non-human leukocyte antigen (HLA)
      antibodies. Case Report: A 50-year-old male underwent an uneventful single lung
      transplant for pulmonary sarcoidosis. Donor and recipient blood type was A
      positive. No pretransplant donor-specific antibodies were identified. Flow
      cytometric crossmatch was negative. The postoperative course was significant for
      a single-unit transfusion of packed red blood cells on postoperative day (POD) 1
      and persistent asymptomatic Serratia marcescens in bronchial washes despite
      ongoing levofloxacin treatment. A surveillance biopsy (POD 34) showed no evidence
      of rejection. One week later (on POD 41), the patient presented with fever,
      shortness of breath, and imaging abnormalities of the grafted lung. Inpatient
      antibiotic escalation to cefepime, ertapenem, and meropenem resolved the positive
      cultures and fever, but the patient's respiratory function continued to decline,
      requiring intubation and extracorporeal membrane oxygenation. High-dose steroids
      and therapeutic plasma exchanges were initiated for suspected acute rejection.
      During the workup, a newly developed anti-A1 red blood cell antibody was
      identified. Despite supportive efforts, the patient died on POD 55, 14 days after
      symptomatic presentation. Conclusion: This case highlights the clinical
      significance of AMR in lung allografts, as well as the need to investigate both
      HLA and non-HLA antibody sources in pulmonary transplant rejection refractory to
      treatment.

PMID- 30275792
TI  - Repetitive Transcranial Magnetic Stimulation for Treatment of Depression in a
      Patient With Severe Traumatic Brain Injury.
AB  - Background: Traumatic brain injury (TBI) commonly presents with a constellation
      of findings, including physical, cognitive, and psychological disturbances.
      Traditionally, few options have been available for long-term management of mood
      symptoms for post-TBI patients who are refractory to medications. Repetitive
      transcranial magnetic stimulation (rTMS) is a promising alternative treatment.
      Case Report: A 37-year-old male with history of anxiety and bipolar depression
      incurred a TBI after a 60-foot fall. After his physical recovery, the patient had
      refractory depression. Eight months after the TBI event, he underwent a 6-week
      course of rTMS treatment and had a 70.8% improvement in mood symptoms by the end
      of the therapy as indicated by the Patient Health Questionnaire-9, transitioning
      from severe to mild depression according to the scoring system. Clinical
      correlation during the months following conclusion of rTMS therapy showed no
      signs of remission or adverse side effects. The patient remains stable and lives
      independently 1 year after treatment with mood-stabilizing medications.
      Conclusion: This case provides evidence for successful treatment of refractory
      depressive symptoms after severe TBI with the addition of rTMS to psychotherapy
      and mood-stabilizing medications, supporting the safety and tolerability of this
      novel therapeutic approach. Further studies are needed to validate the
      contribution of rTMS for management of mood symptoms in patients with TBI.

PMID- 30275793
TI  - Iatrogenic Spinal Epidural Hematoma in the Acute Postoperative Period.
AB  - Background: Spinal epidural hematomas (SEHs) are a rare but serious complication
      associated with spinal surgery, with an incidence estimated to be as high as 3%.
      Patients present with back pain and neurologic symptoms, with a typical onset
      time of several hours to days following surgery. Case Report: A 60-year-old
      female who underwent cervical spine surgery had negative intraoperative
      neuromonitoring and no apparent neurologic deficits of the upper extremities
      immediately postsurgery. On arrival in the postanesthesia care unit, the patient
      reported a loss of sensation in her lower extremities, prompting the
      anesthesiology resident to perform a focused neurologic examination. The patient
      demonstrated 0/5 motor strength in the lower extremities and total loss of
      sensation to touch and temperature up to the level of T10 bilaterally. She was
      returned to the operating room, and surgical exploration revealed a cervical SEH.
      Decompression yielded abrupt return of motor evoked potentials and improvement in
      somatosensory evoked potentials. Conclusion: As the primary clinician in the
      perioperative period, the anesthesiologist is ideally positioned to be the first
      to detect any deterioration in a patient's condition. Anesthesiologists should be
      cognizant of the potential for acute presentation of SEH so that it can be
      considered in the differential diagnosis.

PMID- 30275794
TI  - Beyond Beck's Triad: A Rare Cause of Cardiac Tamponade and Hemoptysis.
AB  - Background: Primary cardiac angiosarcoma (CAS) is a rare tumor with a dismal
      prognosis. Many patients present with noncardiac symptoms related to metastatic
      disease that could delay the diagnosis and deteriorate the outcome. Case Report:
      A 36-year-old male presented with hemoptysis. Initial imaging and biopsies were
      inconclusive, but a repeat transthoracic echocardiogram to evaluate the patient's
      pericardial effusion showed a mass inferior to the right atrium and invading the
      wall. Biopsy results from 3 different sites confirmed the diagnosis of CAS.
      However, the patient's course was complicated with respiratory failure that
      ultimately led to his death. Autopsy demonstrated CAS involving the full
      thickness of the right atrium and pericardial tissue, with a diffuse metastatic
      process involving the lung, brain, and stomach. Conclusion: The case highlights
      the importance of having an increased level of suspicion for cardiac malignancy
      among young patients presenting with noncardiac symptoms.

PMID- 30275795
TI  - Metastatic Renal Cell Carcinoma Presenting as a Bleeding Gastric Polyp.
AB  - Background: Renal cell carcinoma (RCC) is responsible for nearly 13,000 deaths in
      the United States every year, predominantly because of metastasis to other bodily
      organs. However, metastasis of RCC to the stomach occurs rarely; it presents as
      solitary or multiple polyps or as ulcers concerning for primary gastric
      carcinoma. Bleeding from metastasis to the stomach is a rare and underrecognized
      cause of gastrointestinal bleeding. We describe a case of gastrointestinal
      bleeding in an elderly female who was found to have a gastric polyp of RCC
      origin. Case Report: An 83-year-old female presented to our hospital for
      evaluation of an acute right basal ganglia hemorrhage after falling at her
      nursing home. Her hospital course was notable for melenic stool and anemia. Upper
      endoscopy revealed a single 40-mm pedunculated polyp and active bleeding on the
      lesser curvature of the stomach. Polypectomy and clipping were performed.
      Pathology was consistent with metastatic clear cell RCC. The patient's family
      declined a referral to oncology for evaluation of the newly diagnosed malignancy
      and opted for hospice care. Conclusion: This case illustrates the potential for
      metastatic RCC to involve the stomach and cause gastrointestinal bleeding and
      anemia. The case also illustrates the role of upper gastrointestinal endoscopy in
      diagnosing and treating metastatic causes of gastrointestinal bleeding.

PMID- 30275796
TI  - Trauma-Induced Conduction Disturbances.
AB  - Background: Electrical disturbances following blunt cardiac injuries are rare but
      can be caused by electrical or structural damage to the heart. We present the
      case of a patient who had conduction abnormalities following blunt traumatic
      injury that were incidentally detected on telemetry. Case Report: A 64-year-old
      female with no history of cardiac disease was brought to the emergency department
      after a motor vehicle collision that resulted in chest wall bruising. The patient
      was found to have L-spine fractures and was admitted for observation. During her
      hospitalization, the patient had multiple episodes of heart block. A temporary
      pacemaker was inserted because of the recurrent episodes, and a dual-chamber
      permanent pacemaker was placed on day 4 of her hospitalization. Conclusion: Heart
      block as a consequence of blunt cardiac injury is rare; however, it needs to be
      recognized as early as possible. Permanent pacemaker placement is usually
      indicated for patients with prolonged or recurrent episodes.

PMID- 30275797
TI  - Patellofemoral Arthroplasty.
AB  - Background: Patellofemoral arthritis is a common cause of anterior knee pain and
      limits flexion-related activities of daily living and exercise. While frequently
      present in bicompartmental and tricompartmental osteoarthritis, patellofemoral
      arthritis can occur in isolation. Patellofemoral arthroplasty as a treatment
      option is gaining in popularity, especially with new implant designs. We report a
      case in which new inlay implants were used to resurface the patellofemoral joint
      in a patient with contralateral compromise secondary to a previous below-knee
      amputation. Case Report: A 37-year-old female with a contralateral right below
      knee amputation and progressive left patellofemoral arthritis had failed multiple
      conservative treatment modalities. She underwent isolated patellofemoral
      arthroplasty using an inlay-designed implant. The patient was followed for 2
      years postoperatively. She noticed an immediate increase in her knee range of
      motion and her pain scores improved. Two years postoperatively, she demonstrated
      drastic improvement in all outcome measures: International Knee Documentation
      Committee score (16.1 to 88.5), Lysholm Knee Scoring Scale (22 to 100), Knee
      Injury and Osteoarthritis Outcome Score (KOOS) Symptoms (7.14 to 96.43), KOOS
      Pain (2.78 to 100), KOOS Activities of Daily Living (0 to 100), KOOS Sports (0 to
      100), and KOOS Quality of Life (12.5 to 93.75). Conclusion: Inlay patellofemoral
      arthroplasty is a valid treatment option for isolated patellofemoral arthritis.
      Successful results can be achieved with this procedure after failure of
      conservative measures in patients with limited or no evidence of tibiofemoral
      arthritis.

PMID- 30275798
TI  - Left Ventricular Aneurysm Presenting as Bidirectional Ventricular Tachycardia.
AB  - Background: Bidirectional ventricular tachycardia is a rare form of ventricular
      arrhythmia, characterized by a changing of the mean QRS axis of 180 degrees.
      Digitalis toxicity is the most common cause of bidirectional ventricular
      tachycardia; other causes include myocarditis, aconite toxicity, metastatic
      cardiac tumor, myocardial infarction, and cardiac channelopathies. Case Report: A
      73-year-old male with hypertension and a pacemaker implanted for sick sinus
      syndrome presented with a complaint of substernal chest pressure for several
      days. He also stated he had had an episode of near syncope. The patient's
      physical examination was unremarkable; however, electrocardiogram demonstrated
      sustained bidirectional ventricular tachycardia. Echocardiogram showed severe
      anterior wall hypokinesis and an estimated ejection fraction of 35%, as well as
      an apical ventricular aneurysm. Electrophysiology study showed that the apical
      ventricular aneurysm was the site of the bidirectional arrhythmia. The patient
      was successfully treated with ventricular tachycardia ablation. Conclusion: This
      case is a unique example of a patient with bidirectional ventricular tachycardia
      originating from an apical left ventricular aneurysm that was treated
      successfully by ablation.

PMID- 30275799
TI  - Antibacterial and Antibiotic-Potentiating Activities of Thirteen Cameroonian
      Edible Plants against Gram-Negative Resistant Phenotypes.
AB  - This work was designed to investigate the antibacterial activities of methanol
      extracts from thirteen Cameroonian edible plants and their antibiotic
      potentiating effects against Gram-negative multidrug-resistant (MDR) phenotypes.
      The broth microdilution method was used to evaluate the minimal inhibitory
      concentration (MIC) and minimal bactericidal concentration (MBC) of the extracts,
      as well as their antibiotic-potentiating activities. The phytochemical screening
      of the extracts was carried out according to the standard methods. The results of
      phytochemical tests revealed the presence of sterols, polyphenols, and tannins in
      most of the tested extracts, with the other classes of secondary metabolites
      being selectively distributed. Tested extracts showed variable antibacterial
      activities with MIC values ranging from 64 to 1024 MUg/mL. However, some extracts
      were significantly active against certain bacterial strains: seeds extract of
      Theobroma cacao (64 MUg/mL) against Escherichia coli AG100Atet and Klebsiella
      pneumoniae K24, and the bark extract of Uapaca guineensis against E. coli ATCC
      8739. The leaves extract of T. cacao displayed the best MBC values (256 MUg/mL)
      against E. aerogenes EA27. Some tested extracts included extracts from the leaves
      of T. cacao and P. vulgaris, and the seeds of D. edulis and barks A. indica has
      selectively improved (2- to 64-fold) the antibacterial activities of some of the
      tested antibiotics, chloramphenicol (CHL), tetracycline (TET), kanamycin (KAN),
      streptomycin (STR), and erythromycin (ERY), against more than 70% of tested MDR
      bacteria. The findings of this work showed that tested plant extracts and
      particularly those from T. cacao and Phaseolus vulgaris can be used alone or in
      combination with conventional antibiotics in the treatment of infections
      involving multiresistant bacteria.

PMID- 30275800
TI  - Parameters Influencing PET Imaging Features: A Phantom Study with Irregular and
      Heterogeneous Synthetic Lesions.
AB  - Aim: To evaluate reproducibility and stability of radiomic features as effects of
      the use of different volume segmentation methods and reconstruction settings. The
      potential of radiomics in really capturing the presence of heterogeneous tumor
      uptake and irregular shape was also investigated. Materials and Methods: An
      anthropomorphic phantom miming real clinical situations including synthetic
      lesions with irregular shape and nonuniform radiotracer uptake was used. 18F-FDG
      PET/CT measurements of the phantom were performed including 38 lesions of
      different shape, size, lesion-to-background ratio, and radiotracer uptake
      distribution. Different reconstruction parameters and segmentation methods were
      considered. COVs were calculated to quantify feature variations over the
      different reconstruction settings. Friedman test was applied to the values of the
      radiomic features obtained for the considered segmentation approaches. Two sets
      of test-retest measurement were acquired and the pairwise intraclass correlation
      coefficient was calculated. Fifty-eight morphological and statistical features
      were extracted from the segmented lesion volumes. A Mann-Whitney test was used to
      evaluate significant differences among each feature when calculated from
      heterogeneous versus homogeneous uptake. The significance of each radiomic
      feature in terms of capturing heterogeneity was evaluated also by testing
      correlation with gold standard indexes of heterogeneity and sphericity. Results:
      The choice of the segmentation method has a strong impact on the stability of
      radiomic features (less than 20% can be considered stable features).
      Reconstruction affects the estimate of radiomic features (only 26% are stable).
      Thirty-one radiomic features (53%) resulted to be reproducible, 11 of them are
      able to discriminate heterogeneity. Among these, we found a subset of 3 radiomic
      features strongly correlated with GS heterogeneity index that can be suggested as
      good features for retrospective evaluations.

PMID- 30275802
TI  - Fluorescent polyacrylate derivate from 4-biphenylmethanol with UV-green emission.
AB  - In this paper we report the synthesis of a new polyacrylate named poly(1,1'
      BP4MA) which is a derivate from 4-biphenylmethanol monomer. Poly(1,1'-BP4MA) was
      obtained by solution and bulk polymerization techniques to yield polymers with
      high molecular weight and high solubility. The study of the optical properties
      showed that poly(1,1'-BP4MA) is a fluorescent material with emission in the UV
      green region and it has similar quantum yield to tryptophan.

PMID- 30275801
TI  - Detecting GPC3-Expressing Hepatocellular Carcinoma with L5 Peptide-Guided
      Pretargeting Approach: In Vitro and In Vivo MR Imaging Experiments.
AB  - Objective: To investigate the potential of L5 peptide-guided pretargeting
      approach to identify GPC3-expressing hepatocellular carcinoma (HCC) using
      ultrasmall superparamagnetic iron oxide (USPIO) as the MR probe. Methods:
      Immunofluorescence with carboxyfluorescein- (FAM-) labeled L5 peptide was
      performed in HepG2 cells. Polyethylene glycol-modified USPIO (PEG-USPIO) and its
      conjugation with streptavidin (SA-PEG-USPIO) were synthesized, and their
      hydrodynamic diameters, zeta potential, T2 relaxivity, and cytotoxicity were
      measured. In vitro and in vivo two-step pretargeting MR imaging was performed on
      HepG2 cells and tumor-bearing mice after the administration of biotinylated L5
      peptide (first step), followed by SA-PEG-USPIO (second step). Prussian blue
      staining was performed to assess iron deposition in tumors. Results: The high
      specificity of L5 peptide for GPC3 was demonstrated. Generation of SA-PEG-USPIO
      nanoparticles with good biocompatibility (an average hydrodynamic diameter of
      35.97 nm and a zeta potential of -7.91 mV), superparamagnetism (R 2 = 0.1039 *
      103 mM-1s-1), and low toxicity was achieved. The pretargeting group showed more
      enhancement than the nonpretargeting group both in vitro (60% vs 20%, P < 0.05)
      and in vivo (32% vs 6%, P < 0.001). Substantial iron deposition was only observed
      in HepG2 cells and tumors in the pretargeting group. Conclusion: L5 peptide
      guided, two-step pretargeting approach with USPIO as the MR imaging probe is a
      lucrative strategy to specifically identify GPC3-expressing HCC.

PMID- 30275803
TI  - Miscibility of poly(acrylic acid)/poly(methyl vinyl ketone) blend and in vitro
      application as drug carrier system.
AB  - A series of poly(acrylic acid)/poly(methyl vinyl ketone) (PAA/PMVK) blends with
      different compositions were prepared by the solvent casting method. The
      miscibility of this pair of polymers was investigated by differential scanning
      calorimetry(DSC), Fourier transform infra-red (FTIR) and X-Ray diffraction (XRD)
      techniques. An in-vitro cytotoxicity test of the drug-carrier system via MTT (3
      (4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay revealed no
      significant cytotoxic effects at concentrations up to 100 ug. ml-1. The STX/PAA
      50 drug carrier systems were also prepared by solvent casting of solutions
      containing the sulfamethoxazole (STX) used as drug model and PAA/PMVK blend in
      N.N-dimethylformamide then crosslinked with acidified ethylene glycol. The
      release dynamic of STX from the prepared hydrogels was investigated in which the
      diffusion through the polymer matrix, the enhancement of the water solubility of
      STX, the influence of the initial drug concentration, the pH of the medium, and
      the effect of the degree of swelling of the polymer matrix on the release dynamic
      was evaluated. According to the total gastrointestinal transit time estimated by
      Belzer, the estimate distribution of STX released in the different organs
      indicated that the performance is obtained with the drug - carrier-system
      containing equal ratios of polymer and 10 wt% of STX (STX-10/PAA-50).

PMID- 30275804
TI  - Clinicopathological Characteristics of Urinary Bladder Tumors in Korean Patients
      20 Years or Younger.
AB  - Background: To investigate the clinicopathological characteristics of urinary
      bladder tumors, a rare malignancy, in patients 20 years or younger. Methods:
      Using a retrospective chart review among patients who received bladder surgery at
      2 institutions between July 1996 and January 2013, we analyzed the
      clinicopathological characteristics of urinary bladder tumors in 21 pediatric
      patients (male:female = 4.25:1.00; mean age, 12.1 years). Results: Pathology
      revealed 9 urothelial tumors, 6 rhabdomyosarcomas, 1 low-grade leiomyosarcoma, 1
      large cell neuroendocrine carcinoma, 1 inflammatory myofibroblastic tumor, and 3
      cases of chronic inflammation without tumors (including 1 xanthogranulomatous
      inflammation). Urothelial tumors (mean patient age, 16.0 years) were benign or
      low-grade; and only transurethral resection of the bladder tumor was necessary
      for treatment. Patients with rhabdomyosarcomas (mean age, 5 years) underwent
      radiotherapy (if unresectable) or transurethral resection of the bladder tumor
      (if resectable), after chemotherapy. Of these patients, 2 underwent radical
      cystectomy, with the remaining patients not receiving a cystectomy. With the
      exception of one patient, all patients are currently alive and recurrence-free.
      Conclusion: Urothelial tumors were the most commonly found pediatric bladder
      tumor, with embryonal rhabdomyosarcoma being the second most common. Urothelial
      tumors are common in relatively older age. Since urothelial tumors in children
      typically have a good prognosis and rarely recur, transurethral resection of the
      bladder tumor is the treatment of choice. Rhabdomyosarcomas are common in younger
      patients. Since rhabdomyosarcoma is generally chemosensitive, chemotherapy and
      radiotherapy are the treatment of choice for bladder preservation in these
      patients.

PMID- 30275805
TI  - Validity, Reliability and Responsiveness of the Korean Version of Quick
      Disabilities of the Arm, Shoulder, and Hand Questionnaire in Patients with Carpal
      Tunnel Syndrome.
AB  - Background: The Quick Disabilities of the Arm, Shoulder, and Hand questionnaire
      (QuickDASH) is one of the most widely used questionnaires for assessing
      functional ability of the patients with upper extremity diseases. Carpal tunnel
      syndrome (CTS) is the most common neuropathic disease in the upper extremities.
      The aim of this study was to verify the validity, reliability, and responsiveness
      of Korean version of QuickDASH questionnaire (K-QuickDASH) in the patients with
      CTS. Methods: In total, 83 subjects who underwent open carpal tunnel release
      (CTR) operation were selected. They fulfilled Korean version of Disabilities of
      the Arm, Shoulder and Hand questionnaire (K-DASH) and K-QuickDASH at two
      different time points: before and six months after the surgery. Both criterion
      related and construct validities were evaluated using Pearson's correlation
      coefficient and factor analysis. Internal consistency was estimated using
      Cronbach's alpha, and test-retest reliability was assessed to verify the
      reliability of K-QuickDASH using intraclass correlation coefficient (ICC). The
      standardized response mean and the effect size were analyzed to confirm the
      responsiveness of the K-QuickDASH in CTS patients. Results: Significant positive
      correlation was found between K-QuickDASH and K-DASH. All the questionnaire items
      were categorized into three factors. Acceptable internal consistency was
      confirmed in three categories of K-QuickDASH. A high test-retest reliability and
      responsiveness of K-QuickDASH were detected. Conclusion: K-QuickDASH in Korean
      patients with CTS was confirmed to have high degree of validity and reliability,
      and responsiveness after CTR. Therefore, the K-QuickDASH would be a good
      evaluation tool for evaluating clinical symptoms and determination of treatment
      outcomes in the patients with CTS.

PMID- 30275807
TI  - Burden of Disease Due to Secondhand Smoke among Korean Adults at Sub-National
      Level.
AB  - Background: Exposure to secondhand smoke (SHS) is one of the biggest health
      hazards. Quantifying the related burden of disease (BOD) is a powerful tool for
      making evidence-based policies. This study calculated the BOD due to SHS at sub
      national level using the most recent statistics of Korea. Methods: SHS related
      diseases were selected by the systematic review of previous studies. Population
      attributable fraction (PAF) was calculated by using the standard formula using
      prevalence of exposure derived from Community Health Survey (CHS) 2013. SHS
      burden was calculated by multiplying nonsmoker's disability adjusted life years
      (DALYs) with PAF of SHS. Results: SHS burden at sub-national level ranged between
      460 DALYs in Cheonan to 5 DALYs in Pyeongtaek, Songtan region. Median of DALY was
      highest in districts of metropolitan cities and lowest in small towns and rural
      areas. Twelve out of fifteen regions with highest DALY per 1,000 were small towns
      and rural areas. Gender and age standardized DALY was highest in Seogwipo (west)
      in Jeju-do (1.66/1,000) and lowest in Dong-gu, Ulsan (0.17/1,000). Conclusion:
      There were substantial variations between regions according to BOD. Regional
      governments should implement policies according to specific situation in each
      region and regular monitoring should be done by calculating BOD. Big cities need
      to focus more on control of active and SHS prevalence. Resources in small towns
      and rural areas need to be allocated more towards implementation of screening
      programs, early diagnosis and treatment of diseases especially in the elderly
      population.

PMID- 30275806
TI  - The Infinity War: How to Cope with Carbapenem-resistant Enterobacteriaceae.
AB  - Carbapenem-resistant Enterobacteriaceae (CRE) are now spread worldwide. In Korea,
      the number of CRE isolation is rapidly increasing, and impending endemicity is a
      concern. To cope well with CRE, thorough infection control, such as active
      surveillance, early detection, strict contact precaution, cleaning the
      environment, and antibiotic stewardship is very important. Therapeutic options
      include polymyxin, tigecycline, fosfomycin or the combination of them with
      carbapenem, which is currently the mainstay of treatment. In addition, various
      combination regimens with new carbapenemase inhibitors such as avibactam,
      vaborbactam, or relebactam, and other classes of antimicrobials such as
      plazomicin and siderophore cephalosporin are in the process of evaluation.

PMID- 30275808
TI  - Outcomes after Arterial or Venous Reconstructions in Limb Salvage Surgery for
      Extremity Soft Tissue Sarcoma.
AB  - Background: Limb salvage surgery with vascular reconstruction is currently
      considered as the standard treatment for extremity soft tissue sarcoma (STS),
      showing equivalent oncologic outcome compared with amputation. In this
      retrospective study, the surgical and functional outcomes after arterial or
      venous reconstruction in limb salvage surgery for STS were analyzed. Methods:
      Consecutive patients who underwent vascular resection and reconstruction as part
      of limb salvage surgery for extremity STS from July 2009 to June 2015 were
      included in this study. Incidence of surgical complication, graft patency, and
      patients' functional outcome were reviewed. Results: During the study period, 14
      arteries and 13 veins were reconstructed in 17 patients (artery only in 4, vein
      only in 3, artery and vein in 10). Autologous great saphenous vein (GSV) was the
      most commonly used vascular conduit in both arterial and venous reconstruction
      (78.6% and 77.0%). The patency of synthetic graft was significantly lower than
      that of the autologous vein conduit (log rank test, P = 0.001). Among 15 patients
      with tumors in lower extremity, 13 were ambulatory after limb salvage surgery.
      During median follow up of 23.3 months (interquartile range 39.9 months), 2
      patients (11.7%) needed amputation of the initially salvaged limb due to local
      recurrence. Conclusion: Limb salvage surgery of soft tissue tumor combined with
      vascular reconstruction showed favorable functional outcome with good local
      control. Autologous vein conduit is preferred over synthetic graft both in
      arterial and venous reconstruction.

PMID- 30275809
TI  - Development of 17 polymorphic microsatellite loci from Jeju striped field mouse,
      Apodemus agrarius chejuensis (Rodentia: Muridae), by 454 pyrosequencing.
AB  - Background: The striped field mouse, Apodemus agrarius, is the most common mammal
      in Korea. Although microsatellite loci for the species have been identified from
      populations in southwestern China, amplification of those markers for Korean
      populations have been unsuccessful. The complicated taxonomy of Korean striped
      field mouse including populations on Jeju Island (A. a chejuensis) necessitates
      identification of additional molecular markers. Findings: We applied 454
      pyrosequencing systems to develop a suite of microsatellite markers. Muscle
      tissue was harvested and sequenced from 30 Jeju striped field mouse specimens
      which yielded 12,165 reads with a mean length per read of 287 bp. From these
      reads, we identified 17 microsatellite loci for A. a. chejuensis and tested these
      new markers against samples of both A. a chejuensis and A. a coreae, the mainland
      taxon. All 17 loci were amplified successfully for both taxa. Of the total 17
      loci, one locus failed to amplify for a population on Heuksan Island. The cross
      species transferability was also tested with the allied taxon, A. peninsulae and
      confirmed successful for 12 loci. Conclusions: These newly developed markers will
      benefit studies of genetic structure, evolution, and resolving taxonomic problems
      of striped field mice and allied taxa in Korea.

PMID- 30275810
TI  - Clinical and Immunological Aspects in Hashimoto's Thyroiditis.
AB  - We propose to establish the relationship between the clinical, functional and
      immunological parameters in a cohort of women with Hashimoto's thyroiditis. The
      study included 68 patients between 19 and 70 who were hospitalized for two years
      in the Endocrinology Clinic of the Hospital in Timisoara. The thyroidal
      dimensions and the aspects of the thyroidal stroma were shown by echography
      examinations. The functional parameters like the serum TSH and free T4
      concentrations were determined by chemiluminescent methods. The immunological
      investigations (antithyroglobulin and antiperoxidase antibodies) were performed
      by the ELISA method. Comparisons were performed by the t test and the Pearson
      correlation analysis. The correlation between the aspects of thyroidal stroma and
      thyroid function revealed hypothyroidism in most cases with moderate (++) or
      severe (+++) echogenity. Another researched aspect was that of correlation of the
      serum levels of TSH with the thyroidal dimension. The following correlations were
      obtained: r= - 0.14 in patients with clinical hypothyroidism and r= - 0.3055 in
      those with subclinical hypothyroidism. The Pearson coefficients for the level of
      TSH in um and those of the antiperoxidase antibodies, according to clinical and
      functional categories, revealed the following results: r= - 0.1580 in patients
      with clinical hypothyroidism and r= - 0.1961 in those with subclinical
      hypothyroidism. Patients with clinical hypothroidism have significant higher
      serum level of TSH as compared with those of the patients with subclinical
      hypothyroidism (p=0.0001). We established a relation between the severe
      hypoechogenity and hypothyroidism status in patients with positive serum
      antibodies (r= 0.5695).

PMID- 30275811
TI  - The Importance of Preanalytical Factors in Immunodiagnostic Testing.

PMID- 30275812
TI  - Cardiovascular Diseases and Homocysteine, a Short Summary of a Long story.

PMID- 30275813
TI  - D-Dimers Test Performed on "Routine" Analysers, a Useful Assay for Rapid
      Investigation in Symptomatic Outpatients with Suspected Pulmonary Embolism.

PMID- 30275814
TI  - Low Prevalence of Hepatitis C Virus Genotype -1b in Chronic Liver Disease
      Patients in India.
AB  - Background: The Hepatitis C Virus (HCV) genome shows significant heterogeneity
      due to a high rate of mutatio; this has a potential bearing on the outcome of
      interferon therapy. Genotype-1b is known to be less responsive to interferon. We
      studied the spectrum of HCV genotypes in chronic liver disease (CLD) patients in
      India. Material and Methods: HCV RNA was extracted from the serum of 44 randomly
      selected cases of HCV-related CLD, proven by liver biopsy, (mean age of patients
      40+/-15 yr., cirrhotic: 32%) and RT PCR was carried out. The amplicon of 240 bp
      (second nested PCR) was hybridized to the probes (type specific) coated on to a
      nitrocellulose membrane. Following this, streptavidin, labeled with alkaline
      phosphatase, was added to bind with biotinylated hybrid, which with chromogen
      type-specific band formation resulted. Patients were classified on the occurrence
      of one (Group I), two (Group II) or multiple genotypes (Group III). Results:
      Genotypes 1 and 3 were the commonest genotypes, followed by type 2 and the rare
      genotype 4b in a lone patient. Genotype 1 was seen in 39% (1a 23%, and 1b 16%)
      while genotype 3 in 45% (3a 23% and 3b 7%) patients. Eighty percent (35 of 44)
      patients had the single genotype (Group I, mean age 46 +/- 8 yr.), 14% had two
      genotypes (Group II, mean age 36 +/- 16 yr.) and the remaining (Group III, mean
      age 22 +/- 9 yr.) had multiple genotypes. Serum ALT levels in these three groups
      of patients were 117 +/- 92, 85 +/- 45 and 49 +/- 7 IU/L respectively.
      Conclusions: Genotypes 1 and 3 are common in India, with subtype 1b not so
      common,A unique genotype 4 b was detected in one patient,Indian patients have the
      possibility of good antiviral response to interferon therapy in chronic HCV
      infection.

PMID- 30275815
TI  - What Evidence is There for Biochemical Testing?

PMID- 30275817
TI  - Corrigendum: The Role of Personality Traits in Young Adult Fruit and Vegetable
      Consumption.
AB  - [This corrects the article DOI: 10.3389/fpsyg.2017.00119.].

PMID- 30275818
TI  - Corrigendum: Natural Killer Cell Activity and Interleukin-12 in Metabolically
      Healthy versus Metabolically Unhealthy Overweight Individuals.
AB  - [This corrects the article DOI: 10.3389/fimmu.2017.01700.].

PMID- 30275816
TI  - GC-B Deficient Mice With Axon Bifurcation Loss Exhibit Compromised Auditory
      Processing.
AB  - Sensory axon T-like branching (bifurcation) in neurons from dorsal root ganglia
      and cranial sensory ganglia depends on the molecular signaling cascade involving
      the secreted factor C-type natriuretic peptide, the natriuretic peptide receptor
      guanylyl cyclase B (GC-B; also known as Npr2) and cGMP-dependent protein kinase I
      (cGKI, also known as PKGI). The bifurcation of cranial nerves is suggested to be
      important for information processing by second-order neurons in the hindbrain or
      spinal cord. Indeed, mice with a spontaneous GC-B loss of function mutation
      (Npr2cn/cn ) display an impaired bifurcation of auditory nerve (AN) fibers.
      However, these mice did not show any obvious sign of impaired basal hearing.
      Here, we demonstrate that mice with a targeted inactivation of the GC-B gene
      (Npr2 lacZ/lacZ , GC-B KO mice) show an elevation of audiometric thresholds. In
      the inner ear, the cochlear hair cells in GC-B KO mice were nevertheless similar
      to those from wild type mice, justified by the typical expression of functionally
      relevant marker proteins. However, efferent cholinergic feedback to inner and
      outer hair cells was reduced in GC-B KO mice, linked to very likely reduced rapid
      efferent feedback. Sound-evoked AN responses of GC-B KO mice were elevated, a
      feature that is known to occur when the efferent axo-dendritic feedback on AN is
      compromised. Furthermore, late sound-evoked brainstem responses were
      significantly delayed in GC-B KO mice. This delay in sound response was
      accompanied by a weaker sensitivity of the auditory steady state response to
      amplitude-modulated sound stimuli. Finally, the acoustic startle response (ASR) -
      one of the fastest auditory responses - and the prepulse inhibition of the ASR
      indicated significant changes in temporal precision of auditory processing. These
      findings suggest that GC-B-controlled axon bifurcation of spiral ganglion neurons
      is important for proper activation of second-order neurons in the hindbrain and
      is a prerequisite for proper temporal auditory processing likely by establishing
      accurate efferent top-down control circuits. These data hypothesize that the
      bifurcation pattern of cranial nerves is important to shape spatial and temporal
      information processing for sensory feedback control.

PMID- 30275819
TI  - Neolignans isolated from twigs of Nectandra leucantha Ness & Mart (Lauraceae)
      displayed in vitro antileishmanial activity.
AB  - Background: The therapeutic arsenal for the treatment of Leishmaniasis is limited
      and includes toxic compounds (antimonials, amphotericin B, pentamidine and
      miltefosine). Given these aspects, the search for new compounds based on
      floristic biodiversity is crucial. In the present work, we report the isolation,
      characterization and antileishmanial activity of six related neolignans (1-6) of
      bioactive extract from Nectandra leucantha (Lauraceae) twigs. Methods: Dried and
      powdered twigs of N. leucantha were exhaustively extracted using n-hexane. The
      crude extract was dereplicated by HPLC/HRESIMS and subjected to column
      chromatography to yield pure compounds 1-6. Their chemical structures were
      identified via NMR and comparison of obtained data with those previously
      published in the literature. Biological assays of compounds 1-6 and their
      respective monomers (eugenol and methyleugenol) were performed using promastigote
      and amastigote forms of Leishmania (L.) infantum. Results: Dereplication
      procedures followed by chemical characterization of isolated compounds by NMR
      enabled the identification of related neolignans 1-6. Neolignans 2, 4 and 6
      showed potential against amastigote forms of L. (L.) infantum (EC50 values of
      57.9, 67.7 and 13.7 MUM, respectively), while compounds 1 and 3 were inactive. As
      neolignans 2-4 are chemically related, it may be suggested that the presence of
      the methoxyl group at C4 constitutes an important structural aspect to increase
      antileishmanial potential against amastigote forms. Compound 6, which consists of
      a methylated derivative of compound 5 (inactive) showed antileishmanial activity
      similar to that of the standard drug miltefosine (EC50 = 16.9 MUM) but with
      reduced toxicity (SI = 14.6 and 7.2, respectively). Finally, two related
      monomers, eugenol and methyleugenol, were also tested and did not display
      activity, suggesting that the formation of dimeric compounds by oxidative
      coupling is crucial for antiparasitic activity of dimeric compounds 2, 4 and 6.
      Conclusion: This study highlights compound 6 against L. (L.) infantum amastigotes
      as a scaffold for future design of new compounds for drug treatment of visceral
      leishmaniasis.

PMID- 30275820
TI  - An Automated Approach for Epilepsy Detection Based on Tunable Q-Wavelet and
      Firefly Feature Selection Algorithm.
AB  - Detection of epileptic seizures using an electroencephalogram (EEG) signals is a
      challenging task that requires a high level of skilled neurophysiologists.
      Therefore, computer-aided detection provides an asset to the neurophysiologist in
      interpreting the EEG. This paper introduces a novel approach to recognize and
      classify the epileptic seizure and seizure-free EEG signals automatically by an
      intelligent computer-aided method. Moreover, the prediction of the preictal phase
      of the epilepsy is proposed to assist the neurophysiologist in the clinic. The
      proposed method presents two perspectives for the EEG signal processing to detect
      and classify the seizures and seizure-free signals. The first perspectives
      consider the EEG signal as a nonlinear time series. A tunable Q-wavelet is
      applied to decompose the signal into smaller segments called subbands. Then a
      chaotic, statistical, and power spectrum features sets are extracted from each
      subband. The second perspectives process the EEG signal as an image; hence the
      gray-level co-occurrence matrix is determined from the image to obtain the
      textures of contrast, correlation, energy, and homogeneity. Due to a large number
      of features obtained, a feature selection algorithm based on firefly optimization
      was applied. The firefly optimization reduces the original set of features and
      generates a reduced compact set. A random forest classifier is trained for the
      classification and prediction of the seizures and seizure-free signals.
      Afterward, a dataset from the University of Bonn, Germany, is used for
      benchmarking and evaluation. The proposed approach provided a significant result
      compared with other recent work regarding accuracy, recall, specificity, F
      measure, and Matthew's correlation coefficient.

PMID- 30275821
TI  - Corrigendum to "A Composite Model of Wound Segmentation Based on Traditional
      Methods and Deep Neural Networks".
AB  - [This corrects the article DOI: 10.1155/2018/4149103.].

PMID- 30275822
TI  - Repulsive Environment Attenuation during Adult Mouse Optic Nerve Regeneration.
AB  - The regenerative capacity of CNS tracts has ever been a great hurdle to
      regenerative medicine. Although recent studies have described strategies to
      stimulate retinal ganglion cells (RGCs) to regenerate axons through the optic
      nerve, it still remains to be elucidated how these therapies modulate the
      inhibitory environment of CNS. Thus, the present work investigated the
      environmental content of the repulsive axon guidance cues, such as Sema3D and its
      receptors, myelin debris, and astrogliosis, within the regenerating optic nerve
      of mice submitted to intraocular inflammation + cAMP combined to conditional
      deletion of PTEN in RGC after optic nerve crush. We show here that treatment was
      able to promote axonal regeneration through the optic nerve and reach visual
      targets at twelve weeks after injury. The Regenerating group presented reduced
      MBP levels, increased microglia/macrophage number, and reduced astrocyte
      reactivity and CSPG content following optic nerve injury. In addition, Sema3D
      content and its receptors are reduced in the Regenerating group. Together, our
      results provide, for the first time, evidence that several regenerative repulsive
      signals are reduced in regenerating optic nerve fibers following a combined
      therapy. Therefore, the treatment used made the CNS microenvironment more
      permissive to regeneration.

PMID- 30275823
TI  - Anatomical and Functional MRI Changes after One Year of Auditory Rehabilitation
      with Hearing Aids.
AB  - Hearing aids (HAs) are an effective strategy for auditory rehabilitation in
      patients with peripheral hearing deficits. Yet, the neurophysiological mechanisms
      behind HA use are still unclear. Thus far, most studies have focused on changes
      in the auditory system, although it is expected that hearing deficits affect a
      number of cognitive systems, notably speech. In the present study, we used
      audiometric evaluations in 14 patients with bilateral hearing loss before and
      after one year of continuous HA use and functional magnetic resonance imaging
      (fMRI) and cortical thickness analysis in 12 and 10 of them compared with a
      normal hearing control group. Prior to HA fitting, fMRI activity was found
      reduced in the auditory and language systems and increased in visual and frontal
      areas, expanding to multimodal integration cortices, such as the superior
      temporal gyrus, intraparietal sulcus, and insula. One year after rehabilitation
      with HA, significant audiometric improvement was observed, especially in free
      field Speech Reception Threshold (SRT) test and functional gain, a measure of HA
      efficiency. HA use increased fMRI activity in the auditory and language cortices
      and multimodal integration areas. Individual fMRI signal changes from all these
      areas were positively correlated with individual SRT changes. Before
      rehabilitation, cortical thickness was increased in parts of the prefrontal
      cortex, precuneus, fusiform gyrus, and middle temporal gyrus. It was reduced in
      the insula, supramarginal gyrus, medial temporal gyrus, occipital cortex,
      posterior cingulate cortex, and claustrum. After HA use, increased cortical
      thickness was observed in multimodal integration regions, particularly the very
      caudal end of the superior temporal sulcus, the angular gyrus, and the inferior
      parietal gyrus/superior temporal gyrus/insula. Our data provide the first
      evidence that one year of HA use is related to functional and anatomical brain
      changes, notably in auditory and language systems, extending to multimodal
      cortices.

PMID- 30275824
TI  - Risk Factors Associated with the Occurrence of Autoimmune Diseases in Adult
      Coeliac Patients.
AB  - Objectives: Autoimmune diseases (AD) may be associated with coeliac disease (CD),
      but specific risk factors have been poorly investigated. The aim of this study
      was to assess the spectrum of AD and its specific risk factors associated in a
      series of adult coeliac patients. Materials and Methods: We performed a single
      center case-control study including adult newly diagnosed CD patients. To
      evaluate the risk factors of the association between AD and CD, 341 coeliac
      patients included were categorized on the basis of AD presence: 91 cases with at
      least one AD and 250 controls without AD were compared for clinical, serological,
      and histological features. Eighty-seven cases were age-gender-matched with 87
      controls. Results: Among 341 CD patients, 26.6% of CD patients had at least one
      AD. Endocrine and dermatological diseases were the most prevalent AD encountered:
      autoimmune thyroiditis was present in 48.4% of cases, psoriasis in 17.6%, and
      type I diabetes and dermatitis herpetiformis in 11%, respectively. At logistic
      regression, factors associated with AD were a positive 1st-degree family history
      of AD (OR 3.7, 95% CI 1.93-7), a body mass index >= 25 kg/m2 at CD diagnosis (OR
      2.95%, CI 1.1-3.8), and long standing presentation signs/symptoms before CD
      diagnosis (>10 years) (OR 2.1, 95% CI 1.1-3.7). Analysis on age-gender-matched
      patients confirmed these results. Conclusions: CD patients with family history of
      AD, overweight at CD diagnosis, and a delay of CD diagnosis had an increased risk
      of having another AD. The benefit of CD screening in these specific subsets of
      patients with AD awaits further investigation.

PMID- 30275825
TI  - The Application of a Macroinvertebrate Indicator in Afrotropical Regions for
      Pesticide Pollution.
AB  - Many biotic integrity indices are not able to isolate community effects due to
      pesticide exposure as the communities also respond to other anthropogenic and
      natural stressors. A macroinvertebrate trait bioindicator system that is
      pesticide specific was therefore developed to overcome these challenges. This
      system, called SPEAR (SPEcies At Risk), was applied in South Africa as an
      indicator to link known pesticide catchment usage to changes in the
      macroinvertebrate community, especially when analytical methods are inconclusive.
      In addition, the SPEARsalinity index within the SPEAR suite of tools was also
      evaluated for its effectiveness in South Africa. The results indicated that all
      of the sites have either been exposed to the same pesticide pressure or not been
      exposed to pesticides as the SPEAR results were similar when compared to the
      pesticide intensity. The interaction with other factors like nutrients or
      salinity was likely a factor that confounded the SPEARpesticides indicator.

PMID- 30275826
TI  - Corrigendum to "Beta-Arrestin 1 Mediates Liver Thyrotropin Regulation of
      Cholesterol Conversion Metabolism via the Akt-Dependent Pathway".
AB  - [This corrects the article DOI: 10.1155/2018/4371396.].

PMID- 30275827
TI  - Corrigendum to "Myoinositol: The Bridge (PONTI) to Reach a Healthy Pregnancy".
AB  - [This corrects the article DOI: 10.1155/2017/5846286.].

PMID- 30275828
TI  - Waist Circumference Coupled with Either HDL-C or TG Can Be Used as a Diagnostic
      Marker for Metabolic Syndrome in Chinese Women with Polycystic Ovary Syndrome.
AB  - Although quite a few polycystic ovary syndrome (PCOS) patients suffering from
      metabolic syndrome (MS) have been reported in previous studies, no reliable and
      early diagnostic biomarkers for MS in PCOS patients have yet been identified. To
      identify early and reliable diagnostic biomarkers for MS in Chinese women with
      PCOS, a total of 401 patients (200 PCOS patients and 201 controls) were enrolled
      in our present study. All of the subjects were examined for anthropometric
      (weight, waist circumference, blood pressure, etc.) and biochemical (fasting
      glucose, serum lipid indices, total testosterone, etc.) parameters. Our results
      showed that the prevalence of MS in the PCOS patients (20.50%) was 6.8-fold
      higher (P < 0.05) than that in the controls (2.99%). Nearly 71.0% of the PCOS
      patients had at least one component of MS, of which dyslipidemia was the most
      prevalent. Furthermore, within the PCOS group, the prevalence of MS increased
      with increasing age and body mass index (BMI). Logistic analysis indicated that
      BMI, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C),
      hypertension, and fasting glucose were significantly associated with the presence
      of MS in PCOS patients. Analysis of the ability of the potential diagnostic
      biomarkers to indicate MS in PCOS patients showed that the PPV, NPV, specificity,
      sensitivity, and Youden's index for waist circumference (WC) coupled with HDL-C
      were 59.68%, 97.10%, 84.28%, 90.24%, and 74.52, respectively, and those for WC
      coupled with TG were 93.33%, 92.35%, 98.74%, 68.29%, and 67.03%, respectively.
      ROC curve analysis showed that the areas under the ROC curves (AUCs) for WC
      coupled with HDL-C and for WC coupled with TG were 0.882 and 0.901, respectively.
      Our present study demonstrates that WC coupled with either HDL-C or TG can be
      used as a relatively early and reliable diagnostic biomarker for MS in Chinese
      PCOS patients.

PMID- 30275829
TI  - Corrigendum to "Different Effects of Myoinositol plus Folic Acid versus Combined
      Oral Treatment on Androgen Levels in PCOS Women".
AB  - [This corrects the article DOI: 10.1155/2016/3206872.].

PMID- 30275830
TI  - Free Testosterone Reflects Metabolic as well as Ovarian Disturbances in
      Subfertile Oligomenorrheic Women.
AB  - Background: Diagnosing polycystic ovary syndrome (PCOS) is based on ovulatory
      dysfunction, ovarian ultrasound data, and androgen excess. Total testosterone is
      frequently used to identify androgen excess, but testosterone is mainly bound to
      sex hormone-binding globulin (SHBG) and albumin. Only 1-2% of nonprotein-bound
      testosterone (so-called free testosterone) is biologically active and responsible
      for androgen action. Moreover, automated immunoassays which are frequently used
      for female testosterone measurements are inaccurate. Objective: To assess the
      clinical usefulness of liquid chromatography-tandem mass spectrometry measured
      testosterone and calculated free testosterone in subfertile women attending a
      fertility clinic with oligomenorrhea and suspected PCOS. Methods: Hormonal and
      metabolic parameters were evaluated, and ovarian ultrasound was performed. Total
      testosterone was measured by liquid chromatography-tandem mass spectrometry. Free
      testosterone was calculated from total testosterone and SHBG. Results: Sixty-six
      women were included in the study. Total testosterone was associated with ovarian
      volume and antral follicle count but not with metabolic parameters. However, SHBG
      and calculated free testosterone were associated with both ovarian ultrasound and
      metabolic parameters, such as BMI and insulin resistance. Conclusions: Assessing
      SHBG and free testosterone is important in evaluating androgen excess in
      subfertile women with ovulatory dysfunction and suspected PCOS, as it reflects
      both ovarian and metabolic disturbances.

PMID- 30275831
TI  - Association between the Anatomy of the Mandibular Canal and Facial Types: A Cone
      Beam Computed Tomography Analysis.
AB  - We evaluated the anatomical variations of the mandibular canal associated with
      various facial types, age, sex, and side of the face studied. We analyzed 348
      hemimandibles in subjects without a history of trauma, lesions in the lower arch,
      or orthognathic or repair surgery in the posterior mandible. Facial type was
      determined using the VERT index. The canal path was classified as Type 1 (a
      large, single structure passing very close to the root tips); Type 2 (a canal
      passing closest to the mandibular base); and Type 3 (a canal present in the
      posterior mandibular region, with a lower canal running through the mandibular
      branch, reaching the anterior region). Bifid canals (type 3) were classified into
      four categories according to the course and number of mandibular canals. The
      brachyfacial and mesofacial types presented a Type 1 canal in 95.5% (n=166) of
      subjects, in dolichofacial types, 68.2% (n=45) presented a Type 2 canal, while in
      the mesofacial type, a lower prevalence of the bifid mandibular canal was
      observed (13.0%, n=23) than in the other facial types. The bifid canal showed
      significant association with facial type only (p < 0.05), but no significant
      association was observed with the anterior loop type (p > 0.05). Facial type is
      significantly associated with the path and morphological variations of the
      mandibular canal, independently of the side of the face studied, age, and sex.

PMID- 30275832
TI  - Shaping Ability of Superelastic and Controlled Memory Nickel-Titanium File
      Systems: An In Vitro Study.
AB  - Improvements in the thermomechanical processing procedures of NiTi wires have led
      to the development of new NiTi instruments that compose mainly of martensite
      crystals, making the wire stable at clinical condition. This study aimed at
      comparing the shaping ability of two rotary nickel-titanium systems manufactured
      from different NiTi wires. Twenty simulated root canals each with a curvature of
      35 degrees  in resin blocks were divided into two groups of 10 canals each.
      Canals in the first group were prepared with superelastic F360 instruments (Gebr.
      Brasseler, Germany) while canals in the second group were prepared using
      controlled memory HyFlex(r)CMTM instruments (Coltene Whaledent, Switzerland).
      Images were taken before canal preparation and after the use of each instrument.
      The assessment of the canal shapes was accomplished with a computer image
      analysis program. Data were statistically analyzed using SPSS program. Within the
      limitation of this in vitro study, HyFlex(r)CMTM instruments remained better
      centered in the apical third of the canals. In most canal segments, no
      significant differences were observed between either system in the amount of
      material removed. Both systems were comparable to each other in regards to their
      ability to enlarge root canal in the same way without procedural errors.

PMID- 30275833
TI  - Selective Preconcentration of Gold from Ore Samples.
AB  - A simple and selective method has been developed for preconcentration of gold in
      ore samples. The method is based on use of N, N-diethyl-N'-benzoylthiourea (DEBT)
      as selective chelating agent and Amberlite XAD-16 as solid sorbent. Sorption
      behavior of gold with DEBT impregnated resin under optimized conditions has been
      studied in batch process. The gold ion capacity of the impregnated resin is
      calculated as 33.48 mg g-1 resin (0.17 mmol g-1 resin). The selective
      preconcentration of metal was examined using gold chelates prepared in column
      process under optimized conditions: pH, flow rate, volume of sample solution,
      nature of eluent, flow rate, and volume of eluent. Under optimum conditions, gold
      ions at the concentration of 0.015 MUg mL-1 with a preconcentration factor of 6.7
      have been determined by flame atomic absorption spectrometry (FAAS). The accuracy
      of the proposed method was validated by the analysis of a Cu-ore (semi-certified)
      supplied by CMC (Cyprus Mining Company, North Cyprus) and a certified reference
      material, Gold Ore (MA-1b Canmet-MMSL). Satisfactory results were obtained with a
      RSD of 7.6%. The highly selective proposed method does not require any
      interference elimination process.

PMID- 30275834
TI  - Toughening of Poly(L-lactide) with Blends of Poly(epsilon-caprolactone-co-L
      lactide) in the Presence of Chain Extender.
AB  - A poly(epsilon-caprolactone-co-L-lactide) copolyester was synthesized and
      employed to toughen poly(L-lactide) (PLLA) by reactive melt blending in the
      presence of an epoxy-based chain extender. The effects of chain extension
      reaction and copolyester content on properties of PLLA-based blends were studied.
      The chain extension reaction reduced crystallinity and melt flow index of
      PLLA/copolyester blends. Meanwhile the copolyester blending improved the
      crystallinities of the chain-extended PLLA up to 20 wt% copolyester. The phase
      compatibility between PLLA matrix and dispersed copolyester phases was enhanced
      by the chain extension reaction. The impact strength of chain-extended PLLA
      increased with the contents of copolyester and chain extender.

PMID- 30275835
TI  - Nasal Carriage of Methicillin-Resistant Staphylococcus aureus among Health Care
      Workers in Tertiary and Regional Hospitals in Dar es Salam, Tanzania.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) among health care workers
      (HCWs) increases the risk of spreading the organism in hospital settings. A cross
      sectional study was conducted between June and October 2016 among HCWs in
      tertiary and regional hospitals in Dar es Salaam, Tanzania, to determine the MRSA
      nasal carriage rate. Nasal swabs were collected from HCWs and cultured on
      mannitol salt agar. S. aureus was identified based on colonial morphology, Gram
      staining, catalase, coagulase, and DNase test results. MRSA was detected using
      the cefoxitin disk. Among 379 HCWs enrolled, 157/379 (41.4%) were colonized with
      S. aureus, of whom 59 (37.6%) were MRSA carriers giving an overall prevalence of
      59/379 (15.6%). MRSA carriage was high among HCWs in Temeke (56.9%) and Amana
      (37.5%) regional hospitals. A high proportion of MRSA carriage was detected among
      nurses (35, 45.5%). MRSA isolates showed high resistance toward kanamycin
      (83.7%), gentamicin (83.1%), ciprofloxacin (71.2%), and trimethoprim
      sulphamethoxazole (46.8%) compared to methicillin-sensitive S. aureus isolates (p
      <= 0.001). In conclusion, we found a high nasal carriage of MRSA and resistance
      to commonly prescribed antimicrobial agents among HCWs. Implementation of
      infection control measures including contact precautions, urgent reporting of
      MRSA laboratory results, and routine MRSA screening of HCWs is highly needed to
      reduce MRSA spreading.

PMID- 30275836
TI  - Haploidentical Stem Cell Transplantation: A Gateway to Infrequent Availability of
      HLA-Matched Related Donors.
AB  - Haploidentical stem cell transplantation provides a plausible alternative for the
      patients when a fully matched donor is unavailable. Historically, the decision of
      considering haploidentical transplant has remained elusive; however, with the
      recent advances, the consideration of haploidentical grafts as a treatment option
      has become more apparent for both allografting for diseases and engraftment
      failure. We are reporting here an anecdotal case of a successful haploidentical
      engraftment in a patient with the prior graft failure of an HLA-matched related
      donor. Since the patient was severely alloimmunized, desensitization protocol was
      utilized before the haploidentical transplant, and the patient after 8 months of
      her second allogeneic transplantation is doing great with successful engraftment,
      no relapse, and no graft-versus-host disease (GVHD). Numerous reports pertinent
      to haploidentical graft have shown favorable outcomes in the graft placement, a
      decline in the rate of GVHD, and an improvement in the morbidity and mortality in
      affected individuals. Based on the current reports, haploidentical
      transplantation might be more feasible and has meaningful implications in the
      situations where matched donors are infrequent.

PMID- 30275837
TI  - Focal Adhesion Kinase and ROCK Signaling Are Switch-Like Regulators of Human
      Adipose Stem Cell Differentiation towards Osteogenic and Adipogenic Lineages.
AB  - Adipose tissue is an attractive stem cell source for soft and bone tissue
      engineering applications and stem cell therapies. The adipose-derived
      stromal/stem cells (ASCs) have a multilineage differentiation capacity that is
      regulated through extracellular signals. The cellular events related to cell
      adhesion and cytoskeleton have been suggested as central regulators of
      differentiation fate decision. However, the detailed knowledge of these molecular
      mechanisms in human ASCs remains limited. This study examined the significance of
      focal adhesion kinase (FAK), Rho-Rho-associated protein kinase (Rho-ROCK), and
      their downstream target extracellular signal-regulated kinase 1/2 (ERK1/2) on
      hASCs differentiation towards osteoblasts and adipocytes. Analyses of osteogenic
      markers RUNX2A, alkaline phosphatase, and matrix mineralization revealed an
      essential role of active FAK, ROCK, and ERK1/2 signaling for the osteogenesis of
      hASCs. Inhibition of these kinases with specific small molecule inhibitors
      diminished osteogenesis, while inhibition of FAK and ROCK activity led to
      elevation of adipogenic marker genes AP2 and LEP and lipid accumulation
      implicating adipogenesis. This denotes to a switch-like function of FAK and ROCK
      signaling in the osteogenic and adipogenic fates of hASCs. On the contrary,
      inhibition of ERK1/2 kinase activity deceased adipogenic differentiation,
      indicating that activation of ERK signaling is required for both adipogenic and
      osteogenic potential. Our findings highlight the reciprocal role of cell adhesion
      mechanisms and actin dynamics in regulation of hASC lineage commitment. This
      study enhances the knowledge of molecular mechanisms dictating hASC
      differentiation and thus opens possibilities for more efficient control of hASC
      differentiation.

PMID- 30275838
TI  - Genome-Wide DNA Methylation Analysis during Osteogenic Differentiation of Human
      Bone Marrow Mesenchymal Stem Cells.
AB  - Bone marrow mesenchymal stem cells (BMSCs) nowadays are regarded as promising
      candidates in cell-based therapy for the regeneration of damaged bone tissues
      that are either incurable or intractable due to the insufficiency of current
      therapies. Recent studies suggest that BMSCs differentiate into osteoblasts, and
      that this differentiation is regulated by some specific patterns of epigenetic
      modifications, such as DNA methylation. However, the potential role of DNA
      methylation modification in BMSC osteogenic differentiation is unclear. In this
      study, we performed a genome-wide study of DNA methylation between the noninduced
      and induced osteogenic differentiation of BMSCs at day 7. We found that the
      majority of cytosines in a CpG context were methylated in induced BMSCs. Our
      results also revealed that, along with the induced osteogenic differentiation in
      BMSCs, the average genomic methylation levels and CpG methylation in
      transcriptional factor regions (TFs) were increased, the CpG methylation level of
      various genomic elements was mainly in the medium-high methylation section, and
      CpG methylation levels in the repeat element had highly methylated levels. The GO
      analysis of differentially methylated region- (DMR-) associated genes (DMGs)
      showed that GO terms, including cytoskeletal protein binding (included in
      Molecular Function GO terms), skeletal development (included in Biological
      Process GO terms), mesenchymal cell differentiation (included in Biological
      Process GO terms), and stem cell differentiation (included in Biological
      Process), were enriched in the hypermethylated DMGs. Then, the KEGG analysis
      results showed that the WNT pathway, inositol phosphate metabolism pathway, and
      cocaine addiction pathway were more correlative with the DMRs during the induced
      osteogenic differentiation in BMSCs. In conclusion, this study revealed the
      difference of methylated levels during the noninduced and induced osteogenic
      differentiation of BMSCs and provided useful information for future works to
      characterize the important function of epigenetic mechanisms on BMSCs'
      differentiation.

PMID- 30275841
TI  - Assessment of Diarrhea and Its Associated Factors in Under-Five Children among
      Open Defecation and Open Defecation-Free Rural Settings of Dangla District,
      Northwest Ethiopia.
AB  - Background: Open defecation (OD) is a widespread problem in the developing world.
      This practice facilitates the transmission of diarrheal diseases. In Ethiopia,
      still the national open defecation rate in 2014 was 34.1% (37.9% in rural and
      8.7% in urban). Objective: To assess diarrheal morbidity in under-five children
      and its associated factors in Dangla district, Northwest Ethiopia, 2016. Methods:
      A community-based comparative cross-sectional study design with a multistage
      random sampling technique was applied. The total sample size was 550 (275 ODF and
      275 OD). Descriptive and inferential statistics were done. Results: A total of
      525 participants were interviewed making the response rate 95.45%. The prevalence
      of diarrhea was 9.9% in ODF and 36.1% in OD kebeles. In ODF kebeles, child
      immunization (AOR = 0.037; 95% CI: 0.006-0.243), latrine presence (AOR = 0.036;
      0.006-0.233), water shortage (AOR = 8.756; 95% CI: 1.130-67.831), and solid waste
      disposal (AOR = 0.143; 95% CI: 0.020-0.998) have statistically significant
      association with diarrhea occurrence. While in OD kebeles child immunization (AOR
      = 0.032; 95 CI: 0.008-0.123), water access of 7.5-15 liters/day (AOR = 0.029; 95%
      CI: 0.006-0.152), water shortage (AOR = 18.478; 95% CI: 4.692-72.760), and proper
      solid waste disposal (AOR = 0.023; 95% CI: 0.005-0.117) have significant
      association with diarrhea occurrence. Conclusions: The overall prevalence of
      under-five diarrhea was low in ODF kebeles as compared with OD kebeles. The study
      showed that child immunization, latrine presence, water shortage in household,
      and solid waste disposal practices had statistically significant association with
      diarrhea occurrence in ODF kebeles, while water access at the individual level,
      water shortage in household, child immunization, and solid waste disposal have
      statistically significant association with diarrhea occurrence in OD kebeles.
      Integrated efforts are needed from the Ministry of Health together with line
      ministries and developmental partners in improving latrine utilization at
      household level, water shortage in households, and solid waste disposal
      practices.

PMID- 30275840
TI  - Prevalence of Human Bocavirus in Africa and Other Developing Countries between
      2005 and 2016: A Potential Emerging Viral Pathogen for Diarrhea.
AB  - Background: Human Bocavirus (HBoV) is an emerging virus discovered in 2005 from
      individuals suffering gastroenteritis and respiratory tract infections. Numerous
      studies related to the epidemiology and pathogenesis of HBoV have been conducted
      worldwide. This review reports on HBoV studies in individuals with acute
      gastroenteritis, with and without respiratory tract infections in Africa between
      2005 and 2016. Material and Method: The search engines of PubMed, Google Scholar,
      and Embase database for published articles of HBoV were used to obtain data
      between 2005 and 2016. The search words included were as follows: studies
      performed in Africa or/other developing countries or/worldwide; studies for the
      detection of HBoV in patients with/without diarrhea and respiratory tract
      infection; studies using standardized laboratory techniques for detection.
      Results: The search yielded a total of 756 publications with 70 studies meeting
      the inclusion criteria. Studies included children and individuals of all age
      groups. HBoV prevalence in Africa was 13% in individuals suffering
      gastroenteritis with/without respiratory tract infection. Conclusion: Reports
      suggest that HBoV infections are increasingly being recognized worldwide.
      Therefore, surveillance of individuals suffering from infections in Africa is
      required to monitor the prevalence of HBoV and help understand the role of HBoV
      in individuals suffering from gastroenteritis with/without respiratory tract
      infection.

PMID- 30275842
TI  - Are Shiftwork and Indoor Work Related to D3 Vitamin Deficiency? A Systematic
      Review of Current Evidences.
AB  - Background: Reported cases of vitamin D3 deficiency have been increasing in
      incidence worldwide. Although there is a lack of consensus relating to optimal
      levels of vitamin D, generally serum 25-(OH)D concentrations lower than 50 nmol/L
      (20 ng/mL) are at least considered to be detrimental to bone health. Aim: Aim of
      this systematic review is to investigate if occupations, and specifically
      shiftworking and indoor working, may be considered as possible contributors to
      the increased incidence of vitamin D3 deficiency in industrialized nations.
      Materials and Methods: Systematic review was performed according to the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement using
      PubMed, Scopus, and ISI Web of Knowledge databases. Results: Overall 90 papers
      were found, 23 articles through PubMed, 30 through Scopus, and 37 through ISI Web
      of Knowledge. Successively, 46 duplicates and 34 articles that did not respect
      the inclusion criteria were excluded. Finally 10 articles were selected: 9 cross
      sectional studies and 1 systematic review. Results of the studies included
      revealed that certain occupations are either suffering from, or have a
      predilection to suffer from, a deficiency of this vitamin. Shiftworkers and
      indoor workers are consistently reported as being the occupational group most
      likely to suffer from a deficiency of vitamin D3. It would appear prudent to
      investigate the potential of providing nutritional education to workers in
      addition to including preventative measures in the workplace.

PMID- 30275839
TI  - Bioprocessing of Mesenchymal Stem Cells and Their Derivatives: Toward Cell-Free
      Therapeutics.
AB  - Mesenchymal stem cells (MSCs) have attracted tremendous research interest due to
      their ability to repair tissues and reduce inflammation when implanted into a
      damaged or diseased site. These therapeutic effects have been largely attributed
      to the collection of biomolecules they secrete (i.e., their secretome). Recent
      studies have provided evidence that similar effects may be produced by utilizing
      only the secretome fraction containing extracellular vesicles (EVs). EVs are cell
      derived, membrane-bound vesicles that contain various biomolecules. Due to their
      small size and relative mobility, they provide a stable mechanism to deliver
      biomolecules (i.e., biological signals) throughout an organism. The use of the
      MSC secretome, or its components, has advantages over the implantation of the
      MSCs themselves: (i) signals can be bioengineered and scaled to specific dosages,
      and (ii) the nonliving nature of the secretome enables it to be efficiently
      stored and transported. However, since the composition and therapeutic benefit of
      the secretome can be influenced by cell source, culture conditions, isolation
      methods, and storage conditions, there is a need for standardization of
      bioprocessing parameters. This review focuses on key parameters within the MSC
      culture environment that affect the nature and functionality of the secretome.
      This information is pertinent to the development of bioprocesses aimed at scaling
      up the production of secretome-derived products for their use as therapeutics.

PMID- 30275843
TI  - Asthma.
AB  - Asthma is the most common respiratory disorder in Canada. Despite significant
      improvement in the diagnosis and management of this disorder, the majority of
      Canadians with asthma remain poorly controlled. In most patients, however,
      control can be achieved through the use of avoidance measures and appropriate
      pharmacological interventions. Inhaled corticosteroids (ICS) represent the
      standard of care for the majority of patients. Combination ICS/long-acting beta2
      agonist inhalers are preferred for most adults who fail to achieve control with
      ICS therapy. Biologic therapies targeting immunoglobulin E or interleukin-5 are
      recent additions to the asthma treatment armamentarium and may be useful in
      select cases of difficult to control asthma. Allergen-specific immunotherapy
      represents a potentially disease-modifying therapy for many patients with asthma,
      but should only be prescribed by physicians with appropriate training in allergy.
      In addition to avoidance measures and pharmacotherapy, essential components of
      asthma management include: regular monitoring of asthma control using objective
      testing measures such as spirometry, whenever feasible; creation of written
      asthma action plans; assessing barriers to treatment and adherence to therapy;
      and reviewing inhaler device technique. This article provides a review of current
      literature and guidelines for the appropriate diagnosis and management of asthma
      in adults and children.

PMID- 30275844
TI  - Atopic dermatitis.
AB  - Atopic dermatitis (AD) is a common, chronic skin disorder that can significantly
      impact the quality of life of affected individuals as well as their families.
      Although the pathogenesis of the disorder is not completely understood, it
      appears to result from the complex interplay between defects in skin barrier
      function, environmental and infectious agents, and immune dysregulation. There
      are no diagnostic tests for AD; therefore, the diagnosis is based on specific
      clinical criteria that take into account the patient's history and clinical
      manifestations. Successful management of the disorder requires a multifaceted
      approach that involves education, optimal skin care practices, anti-inflammatory
      treatment with topical corticosteroids and/or topical calcineurin inhibitors, the
      management of pruritus, and the treatment of skin infections. Systemic
      immunosuppressive agents may also be used, but are generally reserved for severe
      flare-ups or more difficult-to-control disease. Topical corticosteroids are the
      first-line pharmacologic treatments for AD, and evidence suggests that these
      agents may also be beneficial for the prophylaxis of disease flare-ups. Although
      the prognosis for patients with AD is generally favourable, those patients with
      severe, widespread disease and concomitant atopic conditions, such as asthma and
      allergic rhinitis, are likely to experience poorer outcomes.

PMID- 30275845
TI  - Allergen-specific immunotherapy.
AB  - Allergen-specific immunotherapy is a potentially disease-modifying therapy that
      is effective for the treatment of allergic rhinitis/conjunctivitis, allergic
      asthma and stinging insect hypersensitivity. However, despite its proven efficacy
      in these conditions, it is frequently underutilized in Canada. The decision to
      proceed with allergen-specific immunotherapy should be made on a case-by-case
      basis, taking into account individual patient factors, such as the degree to
      which symptoms can be reduced by avoidance measures and pharmacological therapy,
      the amount and type of medication required to control symptoms, the adverse
      effects of pharmacological treatment, and patient preferences. Since this form of
      therapy carries a risk of anaphylactic reactions, it should only be prescribed by
      physicians who are adequately trained in the treatment of allergic conditions.
      Furthermore, for subcutaneous therapy, injections must be given under medical
      supervision in clinics that are equipped to manage anaphylaxis. In this article,
      the authors review the indications and contraindications, patient selection
      criteria, and details regarding the administration, safety and efficacy of
      allergen-specific immunotherapy.

PMID- 30275846
TI  - Non-IgE-mediated food hypersensitivity.
AB  - Non-immunoglobulin E (IgE)-mediated food hypersensitivity includes a spectrum of
      disorders that predominantly affect the gastrointestinal tract. This review will
      focus on the following more common non-IgE-mediated food hypersensitivity
      syndromes: food protein-induced enterocolitis syndrome (FPIES), allergic
      proctocolitis (AP), food protein-induced enteropathy (FPE) and celiac disease.
      FPIES, AP and FPE typically present in infancy and are most commonly triggered by
      cow's milk protein or soy. The usual presenting features are profuse emesis and
      dehydration in FPIES; blood-streaked and mucousy stools in AP; and protracted
      diarrhea with malabsorption in FPE. Since there are no confirmatory noninvasive
      diagnostic tests for most of these disorders, the diagnosis is based on a
      convincing history and resolution of symptoms with food avoidance. The mainstay
      of management for FPIES, AP and FPE is avoidance of the suspected inciting food,
      with periodic oral food challenges to assess for resolution, which generally
      occurs in the first few years of life. Celiac disease is an immune-mediated
      injury caused by the ingestion of gluten that leads to villous atrophy in the
      small intestine in genetically susceptible individuals. Serologic tests and small
      intestinal biopsy are required to confirm the diagnosis of celiac disease, and
      management requires life-long adherence to a strict gluten-free diet.

PMID- 30275847
TI  - Early introduction of foods to prevent food allergy.
AB  - Food allergy is a growing public health problem, and in many affected
      individuals, the food allergy begins early in life and persists as a lifelong
      condition (e.g., peanut allergy). Although early clinical practice guidelines
      recommended delaying the introduction of peanut and other allergenic foods in
      children, this may have in fact contributed to the dramatic increase in the
      prevalence of food allergy in recent decades. In January 2017, new guidelines on
      peanut allergy prevention were released which represented a significant paradigm
      shift in early food introduction. Development of these guidelines was prompted by
      findings from the Learning Early About Peanut Allergy study-the first randomized
      trial to investigate early allergen introduction as a strategy to prevent peanut
      allergy. This article will review and compare the new guidelines with previous
      guidelines on food introduction, and will also review recent evidence that has
      led to the paradigm shift in early food introduction.

PMID- 30275848
TI  - Eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EoE) is an atopic condition of the esophagus that has
      become increasingly recognized over the last 15 years. Diagnosis of the disorder
      is dependent on the patient's clinical manifestations, and must be confirmed by
      histologic findings on esophageal mucosal biopsies. Patients with EoE should be
      referred to an allergist for optimal management, which may include dietary
      modifications and pharmacologic agents such as corticosteroids, and for the
      diagnosis and management of comorbid atopic conditions. Mechanical dilation of
      the esophagus may also be necessary. The epidemiology, pathophysiology,
      diagnosis, treatment, and prognosis of EoE are discussed in this review.

PMID- 30275849
TI  - Drug allergy.
AB  - Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity
      reactions with varying mechanisms and clinical presentations. This type of
      adverse drug reaction not only affects patient quality of life, but may also lead
      to delayed treatment, unnecessary investigations, and even mortality. Given the
      myriad of symptoms associated with the condition, diagnosis is often challenging.
      Therefore, referral to an allergist experienced in the identification, diagnosis
      and management of drug allergy is recommended if a drug-induced allergic reaction
      is suspected. Diagnosis relies on a careful history and physical examination and,
      in some instances, skin testing and graded challenges. Induction of drug
      tolerance procedures may also be required. The most effective strategy for the
      management of drug allergy is avoidance or discontinuation of the offending drug.
      When available, alternative medications with unrelated chemical structures should
      be substituted. Cross-reactivity among drugs should be taken into consideration
      when choosing alternative agents. Additional therapy for drug hypersensitivity
      reactions is largely supportive and may include topical corticosteroids, oral
      antihistamines and, in severe cases, systemic corticosteroids. In the event of
      anaphylaxis, the treatment of choice is injectable epinephrine. If a particular
      drug to which the patient is allergic is indicated and there is no suitable
      alternative, induction of drug tolerance procedures may be considered to induce
      temporary tolerance to the drug. This article provides a background on drug
      allergy and strategies for the diagnosis and management of some of the most
      common drug-induced allergic reactions, such as penicillin, sulfonamides,
      cephalosporins, radiocontrast media, local anesthetics, general anesthetics,
      acetylsalicylic acid and non-steroidal anti-inflammatory drugs, and therapeutic
      monoclonal antibodies.

PMID- 30275850
TI  - Primary immunodeficiency.
AB  - Primary immunodeficiency disorder (PID) refers to a large heterogeneous group of
      disorders that result from defects in immune system development and/or function.
      PIDs are broadly classified as disorders of adaptive immunity (i.e., T cell, B
      cell or combined immunodeficiencies) or of innate immunity (e.g., phagocyte and
      complement disorders). Although the clinical manifestations of PIDs are highly
      variable, many disorders involve an increased susceptibility to infection. Early
      consultation with a clinical immunologist is essential, as timely diagnosis and
      treatment are imperative for preventing significant disease-associated morbidity.
      PIDs should be suspected in patients with: recurrent sinus or ear infections or
      pneumonias within a 1 year period; failure to thrive; poor response to prolonged
      use of antibiotics; persistent thrush or skin abscesses; or a family history of
      PID. Patients with multiple autoimmune diseases should also be evaluated.
      Diagnostic testing often involves lymphocyte proliferation assays, flow
      cytometry, measurement of serum immunoglobulin (Ig) levels, assessment of serum
      specific antibody titers in response to vaccine antigens, neutrophil function
      assays, stimulation assays for cytokine responses, and complement studies. The
      treatment of PIDs is complex and generally requires both supportive and
      definitive strategies. Ig replacement therapy is the mainstay of therapy for B
      cell disorders, and is also an important supportive treatment for many patients
      with combined immunodeficiency disorders. The disorders affecting the activity of
      the T-cell arm of the adaptive system, such as severe combined immunodeficiency,
      require immune reconstitution as soon as possible. The treatment of innate
      immunodeficiency disorders varies depending on the type of defect, but may
      involve antifungal and antibiotic prophylaxis, cytokine replacement, vaccinations
      and bone marrow transplantation. This article provides an overview of the major
      categories of PIDs and strategies for the appropriate diagnosis and management of
      these rare disorders.

PMID- 30275852
TI  - Patterns of Practice in Radiotherapy for Breast Cancer in Korea.
AB  - Adjuvant radiotherapy (RT) is a well-established treatment for breast cancer.
      However, there is a large degree of variation and controversy in practice
      patterns. A nationwide survey on the patterns of practice in breast RT was
      designed by the Division for Breast Cancer of the Korean Radiation Oncology
      Group. All board-certified members of the Korean Society for Radiation Oncology
      were sent a questionnaire comprising 39 questions on six domains:
      hypofractionated whole breast RT, accelerated partial breast RT, postmastectomy
      RT (PMRT), regional nodal RT, RT for ductal carcinoma in situ, and RT toxicity.
      Sixty-four radiation oncologists from 54 of 86 (62.8%) hospitals responded.
      Twenty-three respondents (35.9%) used hypofractionated whole breast RT, and the
      most common schedule was 43.2 Gy in 16 fractions. Only three (4.7%) used
      accelerated partial breast RT. Five (7.8%) used hypofractionated PMRT, and 40
      (62.5%) had never used boost RT after chest wall irradiation. Indications for
      regional nodal RT varied; >=pN2 (n=7) versus >=pN1 (n=17) versus >=pN1 with
      pathologic risk factors (n=40). Selection criteria for internal mammary lymph
      node (IMN) irradiation also varied; only four (6.3%) always treated IMN when
      regional nodal RT was administered and 30 (46.9%) treated IMN only if IMN
      involvement was identified through imaging. Thirty-one (48.4%) considered
      omission of whole breast RT after breast-conserving surgery for ductal carcinoma
      in situ based on clinical and pathologic risk factors. Fifty-two (81.3%) used
      heart-sparing techniques. Overall, there were wide variations in the patterns of
      practice in breast RT in Korea. Standard guidelines are needed, especially for
      regional nodal RT and omission of RT for ductal carcinoma in situ.

PMID- 30275853
TI  - Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer
      by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis
      Inhibitor 1 In Vivo.
AB  - Purpose: Multidrug resistance (MDR) remains a major obstacle in the treatment of
      triple-negative breast cancer (TNBC) with conventional chemotherapeutic agents. A
      previous study demonstrated that hsa-miRNA-143-3p plays a vital role in drug
      resistance of TNBC. Downregulation of hsa-miRNA-143-3p upregulated the expression
      of its target protein cytokine-induced apoptosis inhibitor 1 (CIAPIN1) in order
      to activate MDR, while upregulation of hsa-miRNA-143-3p effectively enhances the
      sensitivity of drug-resistant TNBC cells to chemotherapeutics. The present study
      aimed to further verify these findings in vivo. Methods: We established a
      hypodermic tumor nude mice model using paclitaxel-resistant TNBC cells. We
      expressed ectopic hsa-miRNA-143-3p under the control of a breast cancer-specific
      human mammaglobin promoter that guided the efficient expression of exogenous hsa
      miRNA-143-3p only in breast cancer cells. Thereafter, we overexpressed hsa-miRNA
      143-3p in xenografts using a recombinant virus system and quantified the
      expression of hsa-miRNA-143-3p, CIAPIN1 protein, and proteins encoded by related
      functional genes by western blot. Results: We successfully completed the
      prospective exploration of the intravenous virus injection pattern from extensive
      expression to targeted expression. The overexpression of hsa-miRNA-143-3p
      significantly alleviated chemoresistance of TNBC by inhibiting viability. In
      addition, we observed that the expression of CIAPIN1 as a hsa-miRNA-143-3p target
      protein was remarkably decreased. Conclusion: We partly illustrated the mechanism
      underlying the hsa-miRNA-143-3p/CIAPIN1 drug resistance pathway. HsamiRNA-143-3p
      as a tumor suppressive microRNA may be a novel target to effectively reverse MDR
      of TNBC in vivo.

PMID- 30275851
TI  - The Epigenetics of Triple-Negative and Basal-Like Breast Cancer: Current
      Knowledge.
AB  - Breast cancer has the highest incidence among all malignancies diagnosed in
      women. Therapies have significantly improved over the years due to extensive
      molecular and clinical research; in a large number of cases, targeted therapies
      have provided better prognosis. However, one specific subtype remains elusive to
      targeted therapies-the triple-negative breast cancer. This immunohistochemically
      defined subtype is resistant to both endocrine and targeted therapies, leading to
      its poor prognosis. A field that is of great promise in current cancer research
      is epigenetics. By studying the epigenetic mechanisms underlying tumorigenesis
      DNA methylation, histone modifications, and noncoding RNAs-advances in cancer
      treatment, diagnosis, and prevention are possible. This review aims to synthesize
      the epigenetic discoveries that have been made related to the triple-negative
      breast cancer.

PMID- 30275854
TI  - Hypoxia-Inducible Factor 1alpha Regulates the Transforming Growth Factor
      beta1/SMAD Family Member 3 Pathway to Promote Breast Cancer Progression.
AB  - Purpose: The transforming growth factor beta1 (TGF-beta1)/SMAD family member 3
      (SMAD3) pathway, and hypoxia-inducible factor 1alpha (HIF-1alpha) are two key
      players in various types of malignancies including breast cancer. The TGF
      beta1/SMAD3 pathway can interact with HIF-1alpha in some diseases; however, their
      interaction in breast cancer is still unknown. Therefore, our study aimed to
      investigate the interactions between the TGF-beta1/SMAD3 pathway and HIF-1alpha
      in breast cancer. Methods: Expression of HIF-1alpha in serum of breast cancer
      patients and healthy controls was detected by quantitative reverse transcription
      polymerase chain reaction, and the diagnostic value of HIF-1alpha for breast
      cancer was evaluated by receiver operating characteristic curve analysis. Breast
      cancer cell lines overexpressing SMAD3 and HIF-1alpha were established. Cell
      apoptosis and proliferation following different treatments were detected by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and cell counting kit
      8, respectively. Expression of related proteins was detected by western blot.
      Results: Serum levels of HIF-1alpha were higher in breast cancer patients than in
      normal controls. Both SMAD3 and HIF-1alpha overexpression inhibited cell
      apoptosis and promoted cell proliferation. Treatment with inhibitors of HIF
      1alpha and SMAD3 promoted apoptosis in breast cancer cells and inhibited their
      proliferation. Overexpression of HIF-1alpha promoted the expression of TGF-beta1
      and SMAD3, while SMAD3 overexpression did not significantly affect expression of
      HIF-1alpha or TGF-beta1. Conclusion: HIF-1alpha serves as an upstream regulator
      of the TGF-beta1/SMAD3 pathway and promotes the growth of breast cancer.

PMID- 30275855
TI  - Deficiency of Follistatin-Like Protein 1 Accelerates the Growth of Breast Cancer
      Cells at Lung Metastatic Sites.
AB  - Purpose: Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein that has
      been shown to play a role in various types of cancer. However, the clinical
      significance and function of FSTL1 in breast cancer have not been reported. We
      investigated the role of FSTL1 in breast cancer in this study. Methods: Enzyme
      linked immunosorbent assays, western blot analysis, and reverse transcription
      polymerase chain reaction were used to monitor the expression of FSTL1 in breast
      cancer tissue and in serum samples from breast cancer patients. We employed a 4T1
      breast cancer model and Fstl1 +/- mice for in vivo studies. Hematoxylin and eosin
      staining, western blot analysis, and RNA sequencing were used to analyze the
      effect of FSTL1 on primary tumor growth and lung metastasis. Results: We
      demonstrated that the expression of FSTL1 is reduced in both the breast cancer
      tissue and the serum of breast cancer patients. We showed that reduced levels of
      FSTL1 in serum correlate with elevated expression of Ki-67 and epidermal growth
      factor receptor (EGFR) in cancer tissues. Moreover, lowered expression of FSTL1
      was associated with decreased survival in breast cancer patients. Experiments on
      the Fstl1 +/- mouse model established that FSTL1 deficiency had no effect on
      primary tumor growth, but increased the lung metastases of breast cancer cells,
      resulting in reduced survival of tumor-bearing mice. RNA sequencing found
      significantly reduced expression of Egln3 and increased expression of EGFR in
      Fstl1 +/- mice. Thus, our results suggest that FSTL1 may affect the expression of
      EGFR through Egln3, inhibiting the proliferation of breast cancer cells at lung
      metastatic sites. Conclusion: In conclusion, we suggest a suppressor role of
      FSTL1 in breast cancer lung metastasis. Furthermore, FSTL1 may represent a
      potential prognostic biomarker and a candidate therapeutic target in breast
      cancer patients.

PMID- 30275856
TI  - Long Noncoding RNA Signature and Disease Outcome in Estrogen Receptor-Positive
      Breast Cancer Patients Treated with Tamoxifen.
AB  - Purpose: Recent data have shown that the expression levels of long noncoding RNAs
      (lncRNAs) are associated with tamoxifen sensitivity in estrogen receptor (ER)
      positive breast cancer. Herein, we constructed an lncRNA-based model to predict
      disease outcomes of ER-positive breast cancer patients treated with tamoxifen.
      Methods: LncRNA expression information was acquired from Gene Expression Omnibus
      by re-mapping pre-existing microarrays of patients with ER-positive breast cancer
      treated with tamoxifen. The distant metastasis-free survival (DMFS) predictive
      signature was subsequently built based on a Cox proportional hazard regression
      model in discover cohort patients, which was further evaluated in another
      independent validation dataset. Results: Six lncRNAs were found to be associated
      with DMFS in the discover cohort, which were used to construct a tamoxifen
      efficacy-related lncRNA signature (TLS). There were 133 and 362 patients with TLS
      high- and low-risk signatures in the discover cohort. Both univariate and
      multivariate analysis demonstrated that TLS was associated with DMFS. TLS high
      risk patients had worse outcomes than low-risk patients, with a hazard ratio of
      4.04 (95% confidence interval, 2.83-5.77; p<0.001). Both subgroup analysis and
      receiver operating characteristic analysis indicated that TLS performed better in
      lymph node-negative, luminal B, 21-gene recurrence score high-risk, and 70-gene
      prognosis signature high-risk patients. Moreover, in a comparison of the 21-gene
      recurrence score and 70-gene prognosis signature, TLS showed a similar area under
      receiver operating characteristic curve in all patients. Gene Set Enrichment
      Analysis indicated that TLS high-risk patients showed different gene expression
      patterns related to the cell cycle and nucleotide metabolism from those of low
      risk patients. Conclusion: This six-lncRNA signature was associated with disease
      outcome in ER-positive breast cancer patients treated with tamoxifen, which is
      comparable to previous messenger RNA signatures and requires further clinical
      evaluation.

PMID- 30275857
TI  - High RNA-binding Motif Protein 3 Expression Is Associated with Improved Clinical
      Outcomes in Invasive Breast Cancer.
AB  - Purpose: Expression of RNA-binding motif protein 3 (RBM3) is induced by hypoxia
      and hypothermia. Recently, high expression of RBM3 was reported to be associated
      with a good prognosis in colon cancer, prostate cancer, ovarian cancer, and
      malignant melanoma. Studies on RBM3 in invasive breast carcinoma (IBC), however,
      are limited. Methods: RBM3 expression was examined using a tissue microarray from
      361 patients with IBC. Immunohistochemistry was performed for estrogen receptor
      (ER), progesterone receptor (PR), human epidermal growth factor receptor 2
      (HER2), and Ki-67 to compare the expression of these markers. For scoring of RBM3
      expression, NF (nuclear staining fraction)*NI (nuclear staining intensity) was
      used. The RBM3 expression score was considered indicative of either low (<=4) or
      high (>4) expression. Western blot analysis was performed on breast cancer cell
      lines to evaluate RBM3 expression. Results: Of the total 361 samples, 240 (66.5%)
      exhibited high RBM3 expression. High RBM3 expression was significantly associated
      with positivity for ER (p<0.001), PR (p<0.001), T stage (p<0.001), histologic
      grade (p<0.001), and % Ki-67 staining (p=0.004). Multivariate analysis revealed
      that high RBM3 expression was closely associated with prolonged disease-free
      survival (DFS) (p<0.001) and overall survival (OS) (p<0.001). Western blot
      analysis revealed reduced RBM3 expression in HCC1954 (HER2-enriched) and BT-20
      (basal-like) cells with an aggressive phenotype. Conclusion: High nuclear RBM3
      expression is strongly associated with a prolonged DFS and OS. Furthermore, RBM3
      expression is closely associated with good prognostic markers such as ER and PR
      in IBC. High nuclear RBM3 expression is, therefore, a critical biomarker of
      favorable clinical outcomes in IBC.

PMID- 30275858
TI  - Expression of DNA Damage Response Proteins and Associations with
      Clinicopathologic Characteristics in Chinese Familial Breast Cancer Patients with
      BRCA1/2 Mutations.
AB  - Purpose: The characteristic expression of DNA damage response proteins in
      familial breast cancers with BRCA1, BRCA2, or non-BRCA1/2 mutations has not been
      analyzed in Chinese patients. Our study aimed to assess the differential
      expression of microcephalin 1 (BRIT1), ATM serine/threonine kinase (ATM),
      checkpoint kinase 2 (CHEK2), BRCA1, RAD51 recombinase (RAD51), and poly (ADP
      ribose) polymerase 1 (PARP-1) and establish the profile of Chinese familial
      breast cancers with different mutation status. Methods: We constructed five
      tissue microarrays from 183 familial breast cancer patients (31 with BRCA1
      mutations; 14 with BRCA2 mutations, and 138 with non-BRCA1/2 mutations). The DNA
      response and repair markers used for immunohistochemistry analysis included
      BRIT1, ATM, CHEK2, BRCA1, RAD51, and PARP-1. The expressions of these proteins
      were analyzed in BRCA1/2 mutated tumors. The association between pathologic
      characteristics with BRCA1/2 mutation status was also analyzed. Results: In
      familial breast cancer patients, BRCA1 mutated tumors were more frequent with
      high nuclear grade, estrogen receptor/progesterone receptor/human epidermal
      growth factor receptor 2 negative, low Ki-67, and positive CK5/6. BRCA1 mutated
      tumors had lower CHEK2 and higher cytoplasmic BRIT1 expression than BRCA2 and non
      BRCA1/2 mutation tumors. BRCA2-associated tumors showed higher CHEK2 and
      cytoplasmic RAD51 expression than those in other groups. Nuclear PARP-1
      expression in BRCA1/2-associated tumors was significantly higher than in non
      BRCA1/2 mutation tumors. Moreover, we found quite a few of negative PARP-1
      expression cases in BRCA1/2 mutated groups. Conclusion: The clinicopathologic
      findings of BRCA1-associated Chinese familial breast cancers were similar to the
      results of other studies. Chinese familial breast cancer patients with BRCA1/2
      mutations might have distinctive expression of different DNA damage response
      proteins. The reduced expression of PARP-1 in Chinese BRCA1/2 mutated breast
      cancer patients could influence the therapeutic outcome of PARP-1 inhibitors.

PMID- 30275859
TI  - Comparative Study between Sentinel Lymph Node Biopsy and Axillary Dissection in
      Patients with One or Two Lymph Node Metastases.
AB  - Purpose: Sentinel lymph node biopsy (SLNB) is a standard axillary surgery in
      early breast cancer. If the SLNB result is positive, subsequent axillary lymph
      node dissection (ALND) is a routine procedure. In 2011, the American College of
      Surgeons Oncology Group Z0011 trial revealed that ALND may not be necessary in
      early breast cancer with one or two positive sentinel lymph nodes. The purpose of
      this study was to compare outcomes among Korean patients with one or two positive
      axillary lymph nodes in the final pathology who did and did not undergo ALND.
      Methods: A total of 131,717 patients from the Korea Breast Cancer Society
      registry database received breast cancer surgery from January 1995 to December
      2014. Inclusion criteria were T stage 1 or 2, one or two positive lymph nodes,
      and having received breast-conserving surgery (BCS), whole breast radiation
      therapy, and no neoadjuvant therapy. We analyzed the differences in disease
      specific survival (DSS) and overall survival (OS) between patients who received
      SLNB only and those who underwent SLNB+ALND. Results: A total 4,442 patients met
      the inclusion criteria, with 1,268 (28.6%) in the SLNB group and 3,174 (71.4%) in
      the SLNB+ALND group. There were no differences in DSS and OS between the two
      groups (p=0.378 and p=0.925, respectively). The number of patients who underwent
      SLNB alone for one or two positive lymph nodes increased continuously from 2004
      to 2014. Conclusion: Korean patients with early breast cancer and 1 or 2 positive
      axillary lymph nodes who received BCS plus SLNB showed no significant difference
      in DSS and OS regardless of whether they received ALND. The findings of this
      retrospective study demonstrate that omitting ALND can be considered when
      treating selected patients with early breast cancer who have one or two positive
      lymph nodes.

PMID- 30275860
TI  - Evaluating the Prediction of Breast Cancer Survival Using Lymph Node Ratio.
AB  - Purpose: Previous oncological studies showed that lymph node ratio (LNR) (ratio
      of number of lymph nodes that tested positive for metastasis to the total number
      of lymph nodes examined) is a negative indicator of cancer survival. The American
      Joint Committee on Cancer (AJCC) staging system incorporates tumor size, lymph
      node involvement, and metastasis in a comprehensive model of cancer progression,
      but LNR alone has been shown to outperform the AJCC system in prognostic and
      survival predictions for various types of cancer. The effectiveness of LNR has
      not been evaluated in breast cancer staging. Evaluating LNR for predicting cancer
      staging in breast cancer has the potential to improve treatment recommendations.
      Methods: The Surveillance, Epidemiology, and End Results dataset was used to
      identify 10,655 breast cancer patients who underwent nodal evaluation from 2010
      to 2013, and their LNRs were calculated. Descriptive statistics of lymph node
      evaluation in the patients are provided. Logistic regression with LNR as the
      continuous independent variable was conducted to determine whether LNR could
      predict cancer progression, coded as regional or distant. Analysis was conducted
      using SPSS version 24. Results: Patient's mean age was 59.43+/-18.62. Logistic
      regression analysis revealed that for every 1.3% increase in LNR, the odds of
      falling into the distant stage of the TNM staging system increased by 13.7% (odds
      ratio, 14.73; 95% confidence interval, 12.00-18.08). Conclusion: LNR, while
      correlated with breast cancer staging, serves as a better predictor of survival.
      Precision staging can influence treatment modality, and improved treatments can
      significantly improve quality of life. Additional research and diagnostic
      examinations using LNR as a potential tool for accurate staging in breast cancer
      patients are warranted.

PMID- 30275861
TI  - Comparison of Oncoplastic Breast-Conserving Surgery and Breast-Conserving Surgery
      Alone: A Meta-Analysis.
AB  - Purpose: The use of oncoplastic reconstruction for breast-conserving surgery
      (BCS) extends benefits beyond merely minimizing poor cosmetic results. However,
      the feasibility and oncological safety of oncoplastic surgery (OPS) are
      controversial. Methods: This meta-analysis aimed to compare the short-term and
      long-term oncological outcomes of BCS alone and BCS plus OPS. Relevant studies
      published before July 2017 in the Embase, the Cochrane Library, PubMed, and Web
      of Science databases were screened and collected. The meta-analysis was performed
      using STATA software (Stata Corp.). Results: A total of 3,789 patients from 11
      studies were included, with 2,691 patients in the BCS-alone group and 1,098
      patients in the BCS plus OPS group. The demographics were similar between both
      groups, and no significant difference was observed in pathological T and N stages
      between the two groups. Re-excision was less common (relative risk [RR], 0.66;
      p=0.009) and the positive-margin rate was lower, but not significantly (RR, 0.83;
      p=0.191), in the BCS plus OPS group than in the BCS-alone group. The local and
      distal recurrence rates were similar in both groups. Both disease-free survival
      (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.96-1.49; p=0.112) and
      overall survival (HR, 1.14; 95% CI, 0.76-1.69; p=0.527) did not differ between
      the two groups. Conclusion: A combination of BCS and OPS is preferred over BCS
      alone for decreasing re-excisions and provides similar long-term survival as BCS
      alone in patients with breast cancer.

PMID- 30275863
TI  - Gasless Robot-Assisted Nipple-Sparing Mastectomy: A Case Report.
AB  - Robotic surgical systems enhance surgical accuracy and efficiency by applying
      advanced technologies such as artificial arm joints to provide higher degrees of
      freedom of movement and high-quality three-dimensional images. However, the
      application of robotic surgical systems to breast surgery has not been widely
      attempted. The robotic system would improve cosmesis by enabling surgery using a
      single small incision. We report the first case of a gasless robot-assisted
      nipple-sparing mastectomy and immediate reconstruction in a patient with early
      breast cancer.

PMID- 30275862
TI  - The Novel Pathogenic Mutation c.849dupT in BRCA2 Contributes to the Nonsense
      Mediated mRNA Decay of BRCA2 in Familial Breast Cancer.
AB  - In this study, we used next-generation sequencing methods to screen 300
      individuals for BRCA1 and BRCA2. A novel mutation (c.849dupT) in BRCA2 was
      identified in a female patient and her unaffected brothers. This mutation leads
      to the truncation of BRCA2 functional domains. Moreover, BRCA2 mRNA expression
      levels in mutation carriers are significantly reduced compared to noncarriers.
      Immunofluorescence and western blot assays showed that this mutation resulted in
      reduced BRCA2 protein expression. Thus, we identified a novel mutation that
      damaged the function and expression of BRCA2 in a family with breast cancer
      history. The pedigree analysis suggested that this mutation is strongly
      associated with familial breast cancer. Genetic counsellors suggest that mutation
      carriers in this family undergo routine screening for breast cancer, as well as
      other malignancies, such as prostate and ovarian cancer. The effects of this
      BRCA2 mutation on drug resistance should be taken into consideration during
      treatment.

PMID- 30275864
TI  - Extraocular Muscles Involvement as the Initial Presentation in Metastatic Breast
      Cancer.
AB  - Orbital metastasis is a rare event, and metastatic disease affecting the
      extraocular muscles is an even less frequent complication of solid tumors.
      Herein, we report an unusual case of ptosis as the initial presentation of an
      invasive breast cancer. A 68-year-old woman presented with III and VI partial
      nerve paresis, secondary to a compressive retrobulbar mass. Magnetic resonance
      imaging revealed an infiltrative lesion involving the extraocular muscles. Tissue
      biopsy yielded a result compatible with metastasis to the orbit, with
      immunohistochemistry analysis suggesting breast as the primary organ. Mammography
      identified an area of architectural distortion; stereotactic wire-guided biopsy
      confirmed the result of the previous orbital biopsy. A positron emission
      tomography scan demonstrated disseminated disease. Palliative chemotherapy with
      bone-modulating agents and subsequent hormonal therapy was proposed.
      Unfortunately, the patient did not respond to therapy and died 38 months after
      diagnosis.

PMID- 30275865
TI  - Moxibustion-Simulating Bipolar Radiofrequency Suppresses Weight Gain and Induces
      Adipose Tissue Browning via Activation of UCP1 and FGF21 in a Mouse Model of Diet
      Induced Obesity.
AB  - Background: Obesity is a pathological condition associated with various diseases
      including diabetes, stroke, arthritis, infertility, and heart disease.
      Moxibustion is widely used to prevent and manage obesity in traditional Asian
      medicine. We tested our hypothesis that moxibustion-simulating bipolar
      radiofrequency (M-RF) can suppress total body and white adipose tissue (WAT)
      weight gain via induction of WAT browning in a mouse model of diet-induced
      obesity (DIO). Methods: We designed an M-RF device that could accurately adjust
      the depth and temperature at which heat stimulation was administered into the
      abdomen of DIO mice. High-fat-fed male C57BL/6 mice were treated with the M-RF
      device every two or three days for three weeks. We then harvested WAT and serum
      from the mice and measured total body and WAT weight, size of adipocytes,
      mitochondrial contents, features of the dead adipocyte environment, and levels of
      uncoupling protein 1 (UCP1) and fibroblast growth factor 21 (FGF21). Results:
      Heat stimulation by M-RF in DIO mice resulted in precise temperature adjustment
      in the mice abdomen, with variance less than 1 degrees C. Additionally, M-RF
      stimulation inhibited body and WAT weight gain, resulting in increased formation
      of beige adipocytes, increased mitochondrial content, and decreased formation of
      dead adipocytes in WAT. Moreover, treatment of M-RF induced expression of UCP1
      and FGF21 in serum and/or epididymal WATs in DIO mice. Conclusion: Heat
      stimulation by M-RF treatment induced upregulation of UCP1 and FGF21 expression
      in serum and/or WATs, which was correlated with reduced total body and WAT weight
      gain in DIO mice.

PMID- 30275866
TI  - Guzhi Zengsheng Zhitongwan, a Traditional Chinese Medicinal Formulation,
      Stimulates Chondrocyte Proliferation through Control of Multiple Genes Involved
      in Chondrocyte Proliferation and Differentiation.
AB  - Chinese materia medica (CMM) are essential components of traditional Chinese
      medicine, and Chinese medicinal formulas consisting of 2 or more types of CMM are
      widely used. These formulations have played a pivotal role in health protection
      and disease control for thousands of years. Guzhi Zengsheng Zhitongwan (GZZSZTW),
      which represents one of the Chinese medicinal formulations, has been used for
      several decades to treat joint diseases. However, the exact molecular mechanism
      underlying its efficacy in treating osteoarthritis remains to be elucidated. In
      the present study, we investigated the effects of GZZSZTW on primary
      chondrocytes. We demonstrated that GZZSZTW significantly promoted chondrocyte
      viability, maintained chondrocytes in a continuous proliferative state, and
      prevented their further differentiation. These effects were achieved by the
      synergistic interactions of various herbs and their active components in GZZSZTW
      through an increase in the expression levels of functional genes participating in
      chondrocyte commitment and proliferation and a decrease in the expression levels
      of genes involved in chondrocyte differentiation. GZZSZTW treatment also
      decreased the expression levels of genes that inhibited chondrocyte
      proliferation. Thus, this study has greatly deepened the current knowledge about
      the molecular effects of GZZSZTW on chondrocytes. It has also shed new light on
      possible strategies to further prevent and treat cartilage-related diseases by
      using traditional Chinese medicinal formulations.

PMID- 30275867
TI  - Development, Characterization, and Evaluation of Novel Broad-Spectrum
      Antimicrobial Topical Formulations from Cymbopogon martini (Roxb.) W. Watson
      Essential Oil.
AB  - Background: Skin infections were the most frequently encountered of all
      infections and the 4th leading cause of nonfatal disease burden. Topical drugs
      have been used for the management of skin infections. The growing concern of drug
      resistance to the topical agents has warned the need for continuous development
      of novel drug. Essential oils are the best candidate for new drug with different
      mode of action and target as they are rich in chemical constituents. Objective:
      To evaluate and develop safe and effective topical antimicrobial formulations
      from essential oil of Cymbopogon martini. Method. Essential oil was extracted
      using hydrodistillation aerial part C. martini and topical formulations were
      prepared in five different semisolid bases. In vitro antimicrobial investigations
      were performed on essential oil and topical formulations. Skin sensitizations of
      the formulations were evaluated using guinea pig maximization. Results: The
      essential oil of C. martini has shown broad-spectrum antimicrobial potency
      against all tested organisms with MIC value ranging from 0.65 to 10 MUg/ml.
      Absolute inhibitions of growth of fungi were observed against Trichophyton
      mentagrophytes and Trichophyton rubrum at concentrations above 1% of oil and
      against Microsporum canis and Trichophyton verrucosum at a concentration of 4%
      oil. Among topical formulations, the highest antimicrobial activity was recorded
      in hydrophilic ointment followed by macrogol blend ointment. The antimicrobial
      activity of oil was higher in fungal pathogen compared to bacteria. Gram positive
      bacteria were more sensitive than gram negative bacteria. Hydrophilic and
      macrogol blend ointment containing 5% oil did not produce any skin sensitization
      on guinea pigs. Conclusion: In conclusion, topical formulations of C. martini
      essential oil can be alternative topical agents with safe broad-spectrum activity
      for the treatment of skin disorder. Further studies should focus on shelf life
      study and clinical study of the product.

PMID- 30275868
TI  - Convergent evolution of the ladder-like ventral nerve cord in Annelida.
AB  - Background: A median, segmented, annelid nerve cord has repeatedly been compared
      to the arthropod and vertebrate nerve cords and became the most used textbook
      representation of the annelid nervous system. Recent phylogenomic analyses,
      however, challenge the hypothesis that a subepidermal rope-ladder-like ventral
      nerve cord (VNC) composed of a paired serial chain of ganglia and somata-free
      connectives represents either a plesiomorphic or a typical condition in annelids.
      Results: Using a comparative approach by combining phylogenomic analyses with
      morphological methods (immunohistochemistry and CLSM, histology and TEM), we
      compiled a comprehensive dataset to reconstruct the evolution of the annelid VNC.
      Our phylogenomic analyses generally support previous topologies. However, the so
      far hard-to-place Apistobranchidae and Psammodrilidae are now incorporated among
      the basally branching annelids with high support. Based on this topology we
      reconstruct an intraepidermal VNC as the ancestral state in Annelida. Thus, a
      subepidermal ladder-like nerve cord clearly represents a derived condition.
      Conclusions: Based on the presented data, a ladder-like appearance of the ventral
      nerve cord evolved repeatedly, and independently of the transition from an
      intraepidermal to a subepidermal cord during annelid evolution. Our
      investigations thereby propose an alternative set of neuroanatomical
      characteristics for the last common ancestor of Annelida or perhaps even
      Spiralia.

PMID- 30275869
TI  - The modular organization of roe deer (Capreolus capreolus) body during ontogeny:
      the effects of sex and habitat.
AB  - Background: As a small artiodactyl, the roe deer (Capreolus capreolus L.) is
      characterized by biological plasticity and great adaptability demonstrated by
      their survival under a wide variety of environmental conditions. In order to
      depict patterns of phenotypic variation of roe deer body this study aims to
      quantify variation during ontogenetic development and determine how sex-specific
      reproductive investment and non-uniform habitat differences relate to phenotypic
      variation and do these differential investments mold the patterns of phenotypic
      variation through modular organisation. Results: Patterns of phenotypic
      correlation among body traits change during the ontogeny of roe deer, with
      differential influence of sex and habitat type. Modularity was found to be a
      feature of closed habitats with trunk+forelimbs+hindlimbs as the best supported
      integration/modularity hypothesis for both sexes. The indices of integration and
      evolvability vary with habitat type, age and sex where increased integration is
      followed by decreased evolvability. Conclusion: This is the first study that
      quantifies patterns of correlation in the roe deer body and finds pronounced
      changes in correlation structure during ontogeny affected by sex and habitat
      type. The correlation structure of the roe deer body is developmentally written
      over the course of ontogeny but we do not exclude the influence of function on
      ontogenetic changes. Modularity arises with the onset of reproduction (subadults
      not being modular) and is differentially expressed in males and females from
      different habitats. Both adult males and females show modularity in primordial,
      closed habitats. Overall, all these findings are important as they provide
      support to the idea that modularity can evolve at the population level and change
      fast within a species.

PMID- 30275870
TI  - Dietary n-3 long-chain polyunsaturated fatty acids upregulate energy dissipating
      metabolic pathways conveying anti-obesogenic effects in mice.
AB  - Background: We previously reported on the anti-obesogenic and anti-inflammatory
      effects associated with n-3 long-chain polyunsaturated fatty acids (LCPUFA) in
      our diet-induced obesity (DIO) mouse model. Two isocaloric high-fat diets (HFDs;
      48 kJ% fat), HFD (HF) and n-3 LCPUFA-enriched HFD (HF/n-3), and a control diet
      (C; 13 kJ% fat) were used. The underlying mechanisms however have largely
      remained unclear. Here, we assessed whether the reduced fat mass reflected n-3
      LCPUFA-induced expression changes in lipid metabolism of the intestine, liver,
      and interscapular brown adipose tissue (iBAT), as well as increased iBAT
      thermogenic capacity. Methods: For HF/n-3, saturated and monounsaturated fatty
      acids were partially substituted by n-3 LCPUFA eicosapentaenoic acid and
      docosahexaenoic acid to achieve a balanced n-6/n-3 PUFA ratio (0.84) compared to
      the unbalanced ratios of HF (13.5) and C (9.85). Intestine, liver and iBAT from
      male C57BL/6 J mice, fed defined soybean/palm oil-based diets for 12 weeks, were
      further analysed. Gene and protein expression analyses, immunohistochemistry and
      correlation analyses for metabolic interactions were performed. Results: Compared
      to HF and C, our analyses suggest significantly diminished de novo lipogenesis
      (DNL) and/or increased hepatic and intestinal fatty acid oxidation (omega
      oxidation and peroxisomal beta-oxidation) in HF/n-3 mice. For iBAT, the
      thermogenic potential was enhanced upon HF/n-3 consistent with upregulated
      expression for uncoupling protein-1 and genes involved in mitochondrial
      biogenesis. In addition, a higher capacity for the supply and oxidation of fatty
      acids was observed and expression and correlation analyses indicated a
      coordinated regulation of energy metabolism and futile cycling of triacylglycerol
      (TAG). Moreover, HF/n-3 significantly increased the number of anti-inflammatory
      macrophages and eosinophils and significantly enhanced the levels of activated
      AMP-activated protein kinase alpha (AMPKalpha), peroxisome proliferator-activated
      receptor alpha (PPARalpha) and fibroblast growth factor 21 (FGF21). Conclusions:
      Our data suggest that by targeting transcriptional regulatory pathways,
      AMPKalpha, and FGF21 as potential mediators, HF/n-3 activated less efficient
      pathways for energy production, such as peroxisomal beta-oxidation, increased ATP
      consumption upon the induction of futile cycling of TAG, and additionally
      increased the thermogenic and oxidative potential of iBAT. Therefore, we consider
      n-3 LCPUFA as the potent inducer for upregulating energy dissipating metabolic
      pathways conveying anti-obesogenic effects in mice.

PMID- 30275871
TI  - Alpha-lipoic acid preserves skeletal muscle mass in type 2 diabetic OLETF rats.
AB  - Background: Increased oxidative stress and impaired antioxidant defense are
      important mechanisms in the pathogenesis of diabetic myopathy. Alpha-lipoic acid
      (ALA) has been indicated as a weight-loss treatment in rodents and humans, but
      studies are limited. In the present study, we aimed to determine the influence of
      ALA, a potent biological antioxidant, on metabolic and growth processes in
      diabetic rat skeletal muscle. Methods: Male 25-week-old type 2 diabetic rats
      (OLETF) were randomly divided into two groups, a control group (OLETF-C) and an
      ALA-treated group (OLETF-ALA) supplemented with 100 mg/kg ALA for 8 weeks. Age
      matched, healthy, nondiabetic LETO (LETO-C) rats were used as controls. Results:
      At 32 weeks of age, body weight was decreased by 6.8%, and the areas under the
      curve of IP-GTT, fasting glucose, and insulin were less in OLETF-ALA rats
      compared with OLETF-C rats. ALA significantly preserved muscle mass and enhanced
      muscle fiber cross-sectional area and fiber frequency percentage in the skeletal
      muscle of OLETF rats. Although the activation of myoD, myogenin, and myostatin in
      gastrocnemius muscle was significantly inhibited in OLETF-ALA rats relative to
      OLETF-C rats, there were no differences in the expression levels of muscle
      atrogin-1 and MuRF1 between the two groups. ALA treatment significantly increased
      the levels of phosphorylated 5'-AMPK, SIRT1, and PGC-1alpha, as well as the
      levels of phosphorylated AKT, mTOR, and p70S6 kinase in OLETF-ALA rats compared
      with OLETF-C rats. In contrast, the levels of phosphorylated p38 MAPK, IRS-1, and
      FOXO1 were decreased in OLETF-ALA rats compared with OLETF-C rats. Conclusions:
      ALA treatment preserved mass in the gastrocnemius muscles of OLETF rats. ALA
      significantly upregulated the AMPK/SIRT1/PGC-1alpha and AKT/mTOR/p70S6K signaling
      pathways in OLETF rat skeletal muscle. Therefore, ALA may be a potential
      therapeutic intervention for skeletal muscle loss in animal models of insulin
      resistance.

PMID- 30275872
TI  - Indoor concentrations of VOCs in beauty salons; association with cosmetic
      practices and health risk assessment.
AB  - Background: The use of cosmetic products in beauty salons emits numerous kinds of
      toxic air pollutants. The objectives of this study were to measure the
      concentrations of benzene, toluene, ethylbenzene, xylene, formaldehyde, and
      acetaldehyde in 20 large beauty salons in Tehran and relate the observed
      concentrations to environmental and occupational characteristics of the salons.
      Methods: Samples were collected from inside and outside air of 20 selected salons
      located in different areas of the city. Several additional parameters were
      recorded during the sampling process including surface area, number of active
      employees, type of ventilation, type of ongoing treatments, temperature,
      humidity. Deterministic and stochastic health risk assessment of the compounds
      were performed. Results: Indoor concentrations of each pollutant were
      significantly higher than its outdoor concentrations. Health risk assessment
      showed that benzene, formaldehyde and acetaldehyde represent a possible cancer
      risk in the beauty salons. In addition, toluene, ethylbenzene, and xylene had
      negligible non-carcinogenic risks. Ventilation with air purifier, and fan with
      open window were more effective than using just a fan. Concentrations of benzene
      and toluene were affected by the number of hair dying treatments. The
      concentration of xylene was affected by the number of hair styling. The
      concentration of formaldehyde was affected by the number of hair styling and
      number of nail treatments. Conclusion: With improved ventilation and requirements
      for reformulated cosmetic, concentrations of toxic air pollutants in beauty
      salons could be reduced.

PMID- 30275873
TI  - Uncovering the barriers to exclusive breastfeeding for mothers living in Dhaka's
      slums: a mixed method study.
AB  - Background: Despite the substantial impact on child and maternal health,
      breastfeeding practices for infants remain at the suboptimum level in Bangladesh.
      Yet the understanding of why these practices are suboptimal, especially
      surrounding urban slum dwelling mothers, is unclear. The purpose of this study
      was to assess early infant feeding practices, examine associations with maternal
      factors, and uncover the facilitators and barriers to early feeding practices in
      selected slums of Dhaka, Bangladesh. Methods: A mixed method study was conducted
      from June to September 2016 using both quantitative and qualitative methods among
      mothers with children under the age of 6 months. The survey included 342 mother
      infant pairs and 18 in-depth interviews were conducted. Univariate and multiple
      logistic regression was used to determine status of early infant feeding
      practices and factors associated with exclusive breastfeeding (EBF) within the
      previous 24 h. Transcripts were coded to uncover the facilitators and barriers
      surrounding early infant feeding practices. Results: Sixty four percent (220/342)
      of mothers initiated breastfeeding within 1 h, 96.5% (330/342) reported feeding
      colostrum, and 36.3% (124/342) infants were EBF in the last 24 h. After adjusting
      for child gender, maternal age, education, diet and household income; infant's
      age (adjusted odds ratio (AOR) for 61-120 days 6.42; 95% CI 3.42, 12.1; AOR for
      121-180 days 45.6; 95% CI 18.33, 113.45), prelacteal feeding (AOR 2.53; 95% CI
      1.14, 4.58), lack of planning for EBF during pregnancy (AOR 4.06; 95% CI 1.09,
      15.12) and infants delivered by cesarean section (AOR 2.76; 95% CI 1.34, 5.67)
      were negatively associated with EBF. During the 18 interviews, eight mothers
      reported a cesarean delivery and none of these mothers initiated breastfeeding
      within 1 h or exclusively breastfed. Moreover, all eight mothers gave their
      infants prelacteal feeds. Conclusions: The status of early infant feeding
      practices in Dhaka's slums was poor. The negative impact of cesarean section on
      all early infant feeding practices was evident in both quantitative and
      qualitative analysis.

PMID- 30275874
TI  - Illness-Death Model in Chronic Disease Epidemiology: Characteristics of a
      Related, Differential Equation and an Inverse Problem.
AB  - Chronic diseases impose a huge burden for mankind. Recently, a mathematical
      relation between the incidence and prevalence of a chronic disease in terms of a
      differential equation has been described. In this article, we study the
      characteristics of this differential equation. Furthermore, we prove the ill
      posedness of a related inverse problem arising in chronic disease epidemiology.
      An example application for the inverse problem about type 1 diabetes in German
      women aged up to 35 years is given.

PMID- 30275875
TI  - Correction to: Problem Management Plus (PM+) in the management of common mental
      disorders in a specialized mental healthcare facility in Pakistan; study protocol
      for a randomized controlled trial.
AB  - [This corrects the article DOI: 10.1186/s13033-017-0147-1.].

PMID- 30275876
TI  - Application of Bayesian networks to GAW20 genetic and blood lipid data.
AB  - Background: Bayesian networks have been proposed as a way to identify possible
      causal relationships between measured variables based on their conditional
      dependencies and independencies. We explored the use of Bayesian network analyses
      applied to the GAW20 data to identify possible causal relationships between
      differential methylation of cytosine-phosphate-guanine dinucleotides (CpGs),
      single-nucleotide polymorphisms (SNPs), and blood lipid trait (triglycerides
      [TGs]). Methods: After initial exploratory linear regression analyses, 2 Bayesian
      networks analyses were performed. First, we used the real data and modeled the
      effects of 4 CpGs previously found to be associated with TGs in the Genetics of
      Lipid Lowering Drugs and Diet Network Study (GOLDN). Second, we used the
      simulated data and modeled the effect of a fictional lipid modifying drug with 5
      known causal SNPs and 5 corresponding CpGs. Results: In the real data we show
      that relationships are present between the CpGs, TGs, and other variables-age,
      sex, and center. In the simulated data, we show, using linear regression, that no
      CpGs and only 1 SNP were associated with a change in TG levels, and, using
      Bayesian network analysis, that relationships are present between the change in
      TG levels and most SNPs, but not with CpGs. Conclusions: Even when the causal
      relationships between variables are known, as with the simulated data, if the
      relationships are not strong then it is challenging to reproduce them in a
      Bayesian network.

PMID- 30275877
TI  - Investigating potential causal relationships between SNPs, DNA methylation and
      HDL.
AB  - Using data on 680 patients from the GAW20 real data set, we conducted Mendelian
      randomization (MR) studies to explore the causal relationships between
      methylation levels at selected probes (cytosine-phosphate-guanine sites [CpGs])
      and high-density lipoprotein (HDL) changes (DeltaHDL) using single-nucleotide
      polymorphisms (SNPs) as instrumental variables. Several methods were used to
      estimate the causal effects at CpGs of interest on DeltaHDL, including a newly
      developed method that we call constrained instrumental variables (CIV). CIV
      performs automatic SNP selection while providing estimates of causal effects
      adjusted for possible pleiotropy, when the potentially-pleiotropic phenotypes are
      measured. For CpGs in or near the 10 genes identified as associated with DeltaHDL
      using a family-based VC-score test, we compared CIV to Egger regression and the
      two-stage least squares (TSLS) method. All 3 approaches selected at least 1CpG in
      2 genes-RNMT;C18orf19 and C6orf141-as showing a causal relationship with
      DeltaHDL.

PMID- 30275878
TI  - Direct and indirect genetic effects on triglycerides through omics and correlated
      phenotypes.
AB  - Even though there has been great success in identifying lipid-associated single
      nucleotide polymorphisms (SNPs), the mechanisms through which the SNPs act on
      each trait are poorly understood. The emergence of large, complex biological data
      sets in well-characterized cohort studies offers an opportunity to investigate
      the genetic effects on trait variability as a way of informing the causal genes
      and biochemical pathways that are involved in lipoprotein metabolism. However,
      methods for simultaneously analyzing multiple omics, environmental exposures, and
      longitudinally measured, correlated phenotypes are lacking. The purpose of our
      study was to demonstrate the utility of the structural equation modeling (SEM)
      approach to inform our understanding of the pathways by which genetic variants
      lead to disease risk. With the SEM method, we examine multiple pathways directly
      and indirectly through previously identified triglyceride (TG)-associated SNPs,
      methylation, and high-density lipoprotein (HDL), including sex, age, and smoking
      behavior, while adding in biologically plausible direct and indirect pathways. We
      observed significant SNP effects (P < 0.05 and directionally consistent) on TGs
      at visit 4 (TG4) for five loci, including rs645040 (DOCK7), rs964184
      (ZPR1/ZNF259), rs4765127 (ZNF664), rs1121980 (FTO), and rs10401969 (SUGP1).
      Across these loci, we identify three with strong evidence of an indirect genetic
      effect on TG4 through HDL, one with evidence of pleiotropic effect on HDL and
      TG4, and one variant that acts on TG4 indirectly through a nearby methylation
      site. Such information can be used to prioritize candidate genes in regions of
      interest, inform mechanisms of action of methylation effects, and highlight
      possible genes with pleiotropic effects.

PMID- 30275879
TI  - Disentangling associations between DNA methylation and blood lipids: a Mendelian
      randomization approach.
AB  - Background: DNA methylation is an epigenetic mechanism that has been proposed as
      a possible link between genetic and environmental determinants of disease. Prior
      studies reported robust associations between the methylation of specific cytosine
      phosphate-guanine (CpG) sites and plasma lipids, namely triglycerides (TGs) and
      high-density lipoprotein cholesterol (HDL-C). However, the causality of the
      observed association remains elusive, hampered by weak instrumental variables for
      methylation status. Aim: We present a novel application of the elastic net
      approach to implement a bidirectional Mendelian randomization approach to
      inferring causal relationships between candidate CpGs and plasma lipids in GAW20
      data. Methods: We used DNA methylation, TGs, and HDL-C measured during the visit
      2. Based on prior findings, we selected 5 methylation markers (cg00574958,
      cg07504977, cg06690548, cg19693031, and cg03717755) related to TGs, 2 markers
      (cg09572125 and cg02650017) related to HDL-C, and 2 markers (cg06500161 and
      cg11024682) related to both traits. We implemented an elastic net approach to
      improve the selection of the genetic instrument for the methylation markers,
      followed by bidirectional Mendelian randomization 2-stage least-squares
      regression. Results: We observed causal effects of blood fasting TGs on the
      methylation levels of cg00574958 (CPT1A) and cg06690548 (SLC7A11). For
      cg00574958, our findings were also consistent with the reverse direction of
      association, that is, from CPT1A methylation to TGs. Conclusions: Current
      evidence does not rule out either direction of association between the
      methylation of the cg00574958 CPT1A locus and plasma TGs, highlighting the
      complexity of lipid homeostasis. We also demonstrated a novel approach to improve
      instrument selection in DNA methylation studies.

PMID- 30275880
TI  - Simulation of a medication and methylation effects on triglycerides in the
      Genetic Analysis Workshop 20.
AB  - The GAW20 simulation data set is based upon the companion Genetics of Lipid
      Lowering Drugs and Diet Network (GOLDN) study fenofibrate clinical trial data set
      that forms the real data example for GAW20. The simulated data problem consists
      of 200 simulated replications of what might happen if we were to repeat the GOLDN
      clinical trial 200 independent times, for these exact same subjects, but using a
      new fictitious drug (called "genomethate") that has a pharmaco-epigenetic effect
      on triglyceride response. For each replication, the pre-genomethate values at
      visits 1 and 2 are constant (ie, pedigree structures, age, sex, all phenotypes,
      covariates, genome-wide association study (GWAS) genotypes, and visit 2
      methylation values), the same as the real GOLDN data across all 200 replications.
      Only the post-genomethate treatment data (ie, methylation and triglyceride levels
      for visits 3 and 4) change across the 200 replications. We postulate a growth
      curve pharmaco-epigenetic response model, in which each patient's response to
      genomethate treatment is individualized, and is dependent upon their genotype as
      well as the methylation state for key genes.

PMID- 30275881
TI  - Network analysis of drug effect on triglyceride-associated DNA methylation.
AB  - Background: DNA methylation, an epigenetic modification, can be affected by
      environmental factors and thus regulate gene expression levels that can lead to
      alterations of certain phenotypes. Network analysis has been used successfully to
      discover gene sets that are expressed differently across multiple disease states
      and suggest possible pathways of disease progression. We applied this framework
      to compare DNA methylation levels before and after lipid-lowering medication and
      to identify modules that differ topologically between the two time points,
      revealing the association between lipid medication and these triglyceride-related
      methylation sites. Methods: We performed quality control using beta-mixture
      quantile normalization on 463,995 cytosine-phosphate-guanine (CpG) sites and
      deleted problematic sites, resulting in 423,004 probes. We identified 14,850
      probes that were nominally associated with triglycerides prior to treatment and
      performed weighted gene correlation network analysis (WGCNA) to construct pre-
      and posttreatment methylation networks of these probes. We then applied both
      WGCNA module preservation and generalized Hamming distance (GHD) to identify
      modules with topological differences between the pre- and posttreatment. For
      modules with structural changes between 2 time points, we performed pathway
      enrichment analysis to gain further insight into the biological function of the
      genes from these modules. Results: Six triglyceride-associated modules were
      identified using pretreatment methylation probes. The same 3 modules were not
      preserved in posttreatment data using both the module-preservation and the GHD
      methods. Top-enriched pathways for the 3 differentially methylated modules are
      sphingolipid signaling pathway, proteoglycans in cancer, and metabolic pathways
      (p values < 0.005). One module in particular included an enrichment of lipid
      related pathways among the top results. Conclusions: The same 3 modules, which
      were differentially methylated between pre- and posttreatment, were identified
      using both WGCNA module-preservation and GHD methods. Pathway analysis revealed
      that triglyceride-associated modules contain groups of genes that are involved in
      lipid signaling and metabolism. These 3 modules may provide insight into the
      effect of fenofibrate on changes in triglyceride levels and these methylation
      sites.

PMID- 30275882
TI  - Integrative methylation score to identify epigenetic modifications associated
      with lipid changes resulting from fenofibrate treatment in families.
AB  - Epigenome-wide association studies (EWAS) have traditionally focused on the
      association test of single epigenetic markers with complex traits. However, it is
      possible that multiple cytosine-phosphate-guanine (CpG) sites at the same locus
      could jointly exert their effects on human traits. Therefore, a region-based test
      that combines multiple markers could be more powerful. We used 2 different region
      based tests to investigate the association between changes in DNA methylation and
      drug response, including the median methylation level test (MMLT) and sequence
      kernel association test (SKAT). No genes were found to be significantly
      associated with the drug response (for triglycerides, the false discovery rate
      ranged from 0.855 to 0.999; for high-density lipoprotein cholesterol, and the
      false discovery rate ranged from 0.584 to 0.915). Further evidence is needed to
      explore potential application of gene-level methylation association analysis.

PMID- 30275883
TI  - A Bayesian mixed modeling approach for estimating heritability.
AB  - Background: A Bayesian mixed model approach using integrated nested Laplace
      approximations (INLA) allows us to construct flexible models that can account for
      pedigree structure. Using these models, we estimate genome-wide patterns of DNA
      methylation heritability (h 2 ), which are currently not well understood, as well
      as h 2 of blood lipid measurements. Methods: We included individuals from the
      Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study with Infinium 450
      K cytosine-phosphate-guanine (CpG) methylation and blood lipid data pre- and
      posttreatment with fenofibrate in families with up to three-generation pedigrees.
      For genome-wide patterns, we constructed 1 model per CpG with methylation as the
      response variable, with a random effect to model kinship, and age and gender as
      fixed effects. Results: In total, 425,791 CpG sites pre-, but only 199,027 CpG
      sites posttreatment were found to have nonzero heritability. Across these CpG
      sites, the distributions of h 2 estimates are similar in pre- and posttreatment
      (pre: median = 0.31, interquartile range [IQR] = 0.16; post: median = 0.34, IQR =
      0.20). Blood lipid h 2 estimates were similar pre- and posttreatment with
      overlapping 95% credibility intervals. Heritability was nonzero for treatment
      effect, that is, the difference between pre- and posttreatment blood lipids.
      Estimates for triglycerides h 2 are 0.48 (pre), 0.42 (post), and 0.21
      (difference); likewise for high-density lipoprotein cholesterol h 2 the estimates
      are 0.61, 0.68, and 0.10. Conclusions: We show that with INLA, a fully Bayesian
      approach to estimate DNA methylation h 2 is possible on a genome-wide scale. This
      provides uncertainty assessment of the estimates, and allows us to perform model
      selection via deviance information criterion (DIC) to identify CpGs with strong
      evidence for nonzero heritability.

PMID- 30275884
TI  - Evidence of batch effects masking treatment effect in GAW20 methylation data.
AB  - Using the real data set from GAW20, we examined changes in the distribution of
      DNA methylation before and after treatment. Paired analysis of differences in
      both mean and variance had grossly inflated type 1 error, suggesting either a
      very large number of changes across the entire epigenome or major non-biological
      issues, such as batch effects. Separate analysis of Infinium I and II probes
      indicated differences in the paired t-test statistics between these two types of
      probes. Examination of combined principal components showed that the first and
      fourth principal components discriminate between the before and after treatment
      measurements, further evidencing the presence of batch effects that make any
      conclusions about treatment effect suspect.

PMID- 30275885
TI  - Genome-wide analysis in multiple-case families: assessing the relationship
      between triglyceride and methylation.
AB  - The main goal of this paper is to estimate the effect of triglyceride levels on
      methylation of cytosine-phosphate-guanine (CpG) sites in multiple-case families.
      These families are selected because they have 2 or more cases of metabolic
      syndrome (primary phenotype). The methylations at the CpG sites are the secondary
      phenotypes. Ascertainment corrections are needed when there is an association
      between the primary and secondary phenotype. We will apply the newly developed
      secondary phenotype analysis for multiple-case family studies to identify CpG
      sites where methylations are influenced by triglyceride levels. Our second goal
      is to compare the performance of the naive approach, which ignores the sampling
      of the families, SOLAR (Sequential Oligogenic Linkage Analysis Routines), which
      adjusts for ascertainment via probands, and the secondary phenotype approach. The
      analysis of possible CpG sites associated with triglyceride levels shows results
      consistent with the literature when using the secondary phenotype approach.
      Overall, the secondary phenotype approach performed well, but the comparison of
      the different approaches does not show significant differences between them.
      However, for genome-wide applications, we recommend using the secondary phenotype
      approach when there is an association between primary and secondary phenotypes,
      and to use the naive approach otherwise.

PMID- 30275887
TI  - Detection and analysis of CpG sites with multimodal DNA methylation level
      distributions and their relationships with SNPs.
AB  - DNA methylation levels at cytosine-phosphate-guanine (CpG) sites with multimodal
      distributions among different samples have been reported recently. One possible
      explanation for such variability is that genetic variants might affect epigenetic
      variation. One obvious case is that mutations such as single-nucleotide
      polymorphisms (SNPs) interrupt CpG sites, resulting in different DNA methylation
      levels for different genotypes. However, the relationship between genetic
      variations and epigenetic differences has not been studied thoroughly, partially
      because of the lack of powerful and robust methods to survey genome-wide CpG
      sites with multimodal methylation level distributions (mmCpGs). In this article,
      we develop a Gaussian mixture-model clustering (GMMC)-based approach to
      systematically detect all mmCpGs across the genome based on the GAW20 data set.
      In total, 3785 and 3847 mmCpGs have been identified in pre- and posttreatment
      data sets, respectively. Result analysis shows that approximately 68 to 70% of
      mmCpGs detected from unrelated individuals either have direct overlaps with SNPs
      or have associations with nearby SNPs, suggesting a strong correlation between
      SNPs and mmCpGs. Comparison with an existing approach illustrates that our GMMC
      based method is more consistent when the number of samples decreases. In
      conclusion, mmCpGs may reveal important connections between genetics and
      epigenetics and they should be carefully identified and evaluated.

PMID- 30275886
TI  - Data for GAW20: genome-wide DNA sequence variation and epigenome-wide DNA
      methylation before and after fenofibrate treatment in a family study of metabolic
      phenotypes.
AB  - GAW20 provided participants with an opportunity to comprehensively examine
      genetic and epigenetic variation among related individuals in the context of drug
      treatment response. GAW20 used data from 188 families (N = 1105) participating in
      the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study
      (clinicaltrials.gov identifier NCT00083369), which included CD4+ T-cell DNA
      methylation at 463,995 cytosine-phosphate-guanine (CpG) sites measured before and
      after a 3-week treatment with fenofibrate, single-nucleotide variation at 906,600
      loci, metabolic syndrome components ascertained before and after the drug
      intervention, and relevant covariates. All GOLDN participants were of European
      descent, with an average age of 48 years. In addition, approximately half were
      women and approximately 40% met the diagnostic criteria for metabolic syndrome.
      Unique advantages of the GAW20data set included longitudinal (3 weeks apart)
      measurements of DNA methylation, the opportunity to explore the contributions of
      both genotype and DNA methylation to the interindividual variability in drug
      treatment response, and the familial relationships between study participants.
      The principal disadvantage of GAW20/GOLDN data was the spurious correlation
      between batch effects and fenofibrate effects on methylation, which arose because
      the pre- and posttreatment methylation data were generated and normalized
      separately, and any attempts to remove time-dependent technical artifacts would
      also remove biologically meaningful changes brought on by fenofibrate. Despite
      this limitation, the GAW20 data set offered informative, multilayered omics data
      collected in a large population-based study of common disease traits, which
      resulted in creative approaches to integration and analysis of inherited human
      variation.

PMID- 30275888
TI  - Using penalized regression to predict phenotype from SNP data.
AB  - Background: In a typical genome-enabled prediction problem there are many more
      predictor variables than response variables. This prohibits the application of
      multiple linear regression, because the unique ordinary least squares estimators
      of the regression coefficients are not defined. To overcome this problem,
      penalized regression methods have been proposed, aiming at shrinking the
      coefficients toward zero. Methods: We explore prediction of phenotype from single
      nucleotide polymorphism (SNP) data in the GAW20 data set using a penalized
      regression approach (LASSO [least absolute shrinkage and selection operator]
      regression). We use 10-fold cross-validation to assess predictive performance and
      10-fold nested cross-validation to specify a penalty parameter. Results: By
      analyzing approximately 600,000 SNPs we find that, when the sample size comprises
      a few hundred individuals, SNP effects are heavily penalized, resulting in a poor
      predictive performance. Increasing the sample size to a few thousand individuals
      results in a much smaller penalization of the true effects, thus greatly
      improving the prediction. Conclusions: LASSO regression results in a heavy
      shrinkage of the regression coefficients, and also requires large sample sizes
      (several thousand individuals) to achieve good prediction.

PMID- 30275889
TI  - Transmission-based association mapping of triglyceride levels in a longitudinal
      framework using quasi-likelihood.
AB  - Complex genetic traits are often characterized by multiple quantitative
      phenotypes. Because values of such phenotypes vary over time, it is thought that
      analyses of longitudinal data on the phenotypes may lead to increased power in
      detecting genetic association. In this paper, we extend a transmission-based
      association test applying quasi-likelihood that has been developed by us to the
      longitudinal framework and to carry out a genome-wide association analysis of
      triglyceride levels based on the data provided in GAW20. We consider different
      phenotype definitions based on administration of fenofibrate and obtain
      significant association findings within genes involved in heart diseases.

PMID- 30275890
TI  - Analysis of genotype by methylation interactions through sparsity-inducing
      regularized regression.
AB  - In this paper, we consider the use of the least absolute shrinkage and selection
      operator (LASSO)-type regression techniques to detect important genetic or
      epigenetic loci in genome-wide association studies (GWAS) and epigenome-wide
      association studies (EWAS). We demonstrate how these techniques can be adapted to
      provide quantifiable uncertainty using stability selection, including explicit
      control of the family-wise error rate. We also consider variants of the LASSO,
      such as the group LASSO, to study genetic and epigenetic interactions. We use
      these techniques to reproduce some existing results on the Genetics of Lipid
      Lowering Drugs and Diet Network (GOLDN) data set, which collects from 991
      individuals blood triglyceride and differential methylation at 464,000 cytosine
      phosphate-guanine (CpG) sites and 761,000 single-nucleotide polymorphisms (SNPs),
      and to identify new research directions. Epigenome-wide and genome-wide models
      based on the LASSO are considered, as well as an interaction model limited to
      chromosome 11. The analyses replicate findings concerning 2 CpGs in carnitine
      palmitoyltransferase 1A (CPT1A). Some suggestions are made regarding potentially
      interesting directions for the analysis of genetic and epigenetic interactions.

PMID- 30275891
TI  - Family-based genome-wide association of inflammation biomarkers and fenofibrate
      treatment response in the GOLDN study.
AB  - In this paper we analyzed whole-genome genetic information provided by GAW20 from
      the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study for family
      data. Lipid levels such as triglycerides (TGs) and high-density lipoprotein (HDL)
      are measured at different time points before and after administration of an anti
      inflammatory drug fenofibrate. Apart from that, the data contain some covariates
      and whole-genome genotype information. We propose 2 novel approaches based on
      Henderson's iterative mixed model to identify associated loci corresponding to
      (a) inflammatory biomarkers like TGs and HDLs together over time, and (b) the
      response to fenofibrate treatment. We developed a mixed-model approach using both
      TG and HDL phenotypes at all 4 time points for a genetic association study
      whereas we used TGs only to study genetic association with response to the drug.
      We expect that use of complete family data in a longitudinal framework under a
      single model involving the appropriate correlation structures would be able to
      exploit the maximum possible information contained in the sample. Our analysis of
      whole-genome single nucleotide polymorphisms (SNPs) and genomic regions
      corresponding to drug treatment finds no significant locus after multiple
      correction. Arguably, the moderately small sample size of the data set, as
      compared to the sample size usually used in genome-wide association studies
      (GWAS), could be a reason for such a result. Nevertheless, we report the top 20
      SNPs associated with the phenotypes, and the top 20 SNPs and genomic regions
      associated with a response to fenofibrate treatment. Application of our methods
      to larger GWAS and further functional validation of the reported top SNPs and
      genomic regions might provide important biological insight into the genetic
      constitution of the trait.

PMID- 30275892
TI  - Identifying fenofibrate responsive CpG sites.
AB  - As part of GAW20, we analyzed the familiality and variability of methylation to
      identify cytosine-phosphate-guanine (CpG) sites responsive to treatment with
      fenofibrate. Methylation was measured at approximately 450,000 sites in pedigree
      members, prior to and after 3 weeks of treatment. Initially, we aimed to identify
      responsive sites by analyzing the pre- and posttreatment methylation changes
      within individuals, but these data exhibited a confounding treatment/batch
      effect. We applied an alternative indirect approach by searching for CpG sites
      whose methylation levels exhibit a genetic response to the drug. We reasoned that
      these sites would exhibit highly familial and variable methylation levels
      posttreatment, but not pretreatment. Using a 0.1% threshold, posttreatment
      sibling correlation (scor) and standard deviation (SD) distributions share 16
      outliers, while the corresponding pretreatment distributions share none.
      Comparing the pre- and posttreatment CpG outliers, 36 (8%) of SD distributions,
      and 449/450 (nearly 100%) of scor distributions differ. Combined, these results
      identify methylation sites within the KIAA1804 and ANAPC2 genes. Each gene also
      has a highly significant methylation quantitative trait locus (meQTL) (KIAA1804:
      p < 1e-200; ANAPC2: p < 3e-248), indicating that methylation levels at these CpG
      sites are driven by meQTL and fenofibrate.

PMID- 30275893
TI  - An efficient analytic approach in genome-wide identification of methylation
      quantitative trait loci response to fenofibrate treatment.
AB  - Background: The study of DNA methylation quantitative trait loci (meQTLs) helps
      dissect regulatory mechanisms underlying genetic associations of human diseases.
      In this study, we conducted the first genome-wide examination of genetic drivers
      of methylation variation in response to a triglyceride-lowering treatment with
      fenofibrate (response-meQTL) by using an efficient analytic approach. Methods:
      Subjects (n = 429) from the GAW20 real data set with genotype and both pre-
      (visit 2) and post- (visit 4) fenofibrate treatment methylation measurements were
      included. Following the quality control steps of removing certain cytosine
      phosphate-guanine (CpG) probes, the post-/premethylation changes (post/pre) were
      log transformed and the association was performed on 208,449 CpG sites. An
      additive linear mixed-effects model was used to test the association between each
      CpG probe and single nucleotide polymorphisms (SNPs) around +/-1 Mb region, with
      age, sex, smoke, batch effect, and principal components included as covariates.
      Bonferroni correction was applied to define the significance threshold (p < 5.6 *
      10- 10, given a total of 89,217,303 tests). Finally, we integrated our response
      meQTL (re-meQTL) findings with the published genome-wide association study (GWAS)
      catalog of human diseases/traits. Results: We identified 1087 SNPs as cis re
      meQTLs associated with 610 CpG probes/sites located in 351 unique gene loci.
      Among these 1087 cis re-meQTL SNPs, 229 were unique and 6 were co-localized at 8
      unique disease/trait loci reported in the GWAS catalog (enrichment p = 1.51 * 10-
      23). Specifically, a lipid SNP, rs10903129, located in intron regions of gene
      TMEM57, was a re-meQTL (p = 3.12 * 10- 36) associated with the CpG probe
      cg09222892, which is in the upstream region of the gene RHCE, indicating a new
      target gene for rs10903129. In addition, we found that SNP rs12710728 has a
      suggestive association with cg17097782 (p = 1.77 * 10- 4), and that this SNP is
      in high linkage disequilibrium (LD) (R2 > 0.8) with rs7443270, which was
      previously reported to be associated with fenofibrate response (p = 5.00 * 10-
      6). Conclusions: By using a novel analytic approach, we efficiently identified
      thousands of cis re-meQTLs that provide a unique resource for further
      characterizing functional roles and gene targets of the SNPs that are most
      responsive to fenofibrate treatment. Our efficient analytic approach can be
      extended to large response quantitative trait locus studies with large sample
      sizes and multiple time points data.

PMID- 30275894
TI  - Analysis of genetic and nongenetic factors influencing triglycerides-lowering
      drug effects based on paired observations.
AB  - Obesity is a risk factor for heart disease, stroke, diabetes, high blood
      pressure, and other chronic diseases. Some drugs, including fenofibrate, are used
      to treat obesity or excessive weight by lowering the level of specific
      triglycerides. However, different groups have different drug sensitivities and,
      consequently, there are differences in drug effects. In this study, we assessed
      both genetic and nongenetic factors that influence drug responses and stratified
      patients into groups based on differential drug effect and sensitivity. Our
      methodology of investigating genetic factors and nongenetic factors is applicable
      to studying differential effects of other drugs, such as statins, and provides an
      approach to the development of personalized medicine.

PMID- 30275895
TI  - Relating drug response to epigenetic and genetic markers using a region-based
      kernel score test.
AB  - In GAW20, we investigated the association of specific genetic regions of interest
      (ROIs) with log-transformed triglyceride (TG) levels following lipid-lowering
      medication using epigenetic and genetic markers. The goal was to incorporate
      kernels for cytosine-phosphate-guanine (CpG) markers and compare the kernels to a
      purely parametric model. Post-treatment TG levels were investigated for post
      methylation data at CpG sites and region-specific SNPs and adjusted for pre
      treatment TG levels and age, in independent individuals only (real data: n = 150;
      simulated data, replicate 84: n = 111). In both data sets, our single-CpG-marker
      results using kernels and linear regression were in good agreement. In the real
      data, we investigated the introns of the CPT1A gene previously reported as
      associated with TG levels as separate ROIs, and were able to find hints of an
      association of cg17058475 and cg00574958 with post-treatment TG levels. In the
      simulated data, we investigated a total of 10 regions, in which the 5 causal and
      5 non-causal markers lie, respectively, with increased methylation variances,
      yielding plausible results for the 3 window sizes. Overall, this indicates that
      kernels for CpG markers are feasible. An interaction regression model for the
      causal SNP with the nearest CpG marker identified an effect for the SNPs with the
      three greatest heritabilities simulated. The simulation model assumed full SNP
      effect only for unmethylated regions decreasing to zero in the case of full
      methylation. Thus, in the context of a clear candidate setting, interaction
      between epigenetic and genetic data may enhance information, albeit nominally,
      even with small sample sizes. Relieving the burden of multiple testing,
      developing kernels further to analyze data from multiple omics jointly is well
      warranted.

PMID- 30275896
TI  - Evaluating the performance of gene-based tests of genetic association when
      testing for association between methylation and change in triglyceride levels at
      GAW20.
AB  - Although methylation data continues to rise in popularity, much is still unknown
      about how to best analyze methylation data in genome-wide analysis contexts.
      Given continuing interest in gene-based tests for next-generation sequencing
      data, we evaluated the performance of novel gene-based test statistics on
      simulated data from GAW20. Our analysis suggests that most of the gene-based
      tests are detecting real signals and maintaining the Type I error rate. The
      minimum p value and threshold-based tests performed well compared to single
      marker tests in many cases, especially when the number of variants was relatively
      large with few true causal variants in the set.

PMID- 30275897
TI  - Reliability of genomic predictions of complex human phenotypes.
AB  - Genome-wide association studies have helped us identify a wealth of genetic
      variants associated with complex human phenotypes. Because most variants explain
      a small portion of the total phenotypic variation, however, marker-based studies
      remain limited in their ability to predict such phenotypes. Here, we show how
      modern statistical genetic techniques borrowed from animal breeding can be
      employed to increase the accuracy of genomic prediction of complex phenotypes and
      the power of genetic mapping studies. Specifically, using the triglyceride data
      of the GAW20 data set, we apply genomic-best linear unbiased prediction (G-BLUP)
      methods to obtain empirical genetic values (EGVs) for each triglyceride phenotype
      and each individual. We then study 2 different factors that influence the
      prediction accuracy of G-BLUP for the analysis of human data: (a) the choice of
      kinship matrix, and (b) the overall level of relatedness. The resulting genetic
      values represent the total genetic component for the phenotype of interest and
      can be used to represent a trait without its environmental component. Finally,
      using empirical data, we demonstrate how this method can be used to increase the
      power of genetic mapping studies. In sum, our results show that dense genome-wide
      data can be used in a wider scope than previously anticipated.

PMID- 30275898
TI  - Genome-wide linkage scan for loci influencing plasma triglyceride levels.
AB  - We conducted a genome-wide linkage scan to detect loci that influence the levels
      of fasting triglycerides in plasma. Fasting triglyceride levels were available at
      4 time points (visits), 2 pre- and 2 post-fenofibrate intervention. Multipoint
      identity-by-descent (MIBD) matrices were derived from genotypes using IBDLD.
      Variance-component linkage analyses were then conducted using SOLAR (Sequential
      Oligogenic Linkage Analysis Routines). We found evidence of linkage (logarithm of
      odds [LOD] >=3) at 5 chromosomal regions with triglyceride levels in plasma. The
      highest LOD scores were observed for linkage to the estimated genetic value
      (additive genetic component) of the log-normalized triglyceride levels in plasma.
      Our results suggest that a chromosome 10 locus at 37 cM (LODpre = 3.01, LODpost =
      3.72) influences fasting triglyceride levels in plasma regardless of the
      fenofibrate intervention, and that loci in chromosomes 1 at 170 cM and 4 at 24 cM
      ceases to affect the triglyceride levels when fenofibrate is present, while the
      regions in chromosomes 6 at 136 to 162 cM and 11 at 39 to 40 cM appear to
      influence triglyceride levels in response to fenofibrate.

PMID- 30275899
TI  - Evaluation of a phenotype imputation approach using GAW20 simulated data.
AB  - Statistical power, which is the probability of correctly rejecting a false null
      hypothesis, is a limitation of genome-wide association studies (GWAS). Sample
      size is a major component of statistical power that can be easily affected by
      missingness in phenotypic data and restrain the ability to detect associated
      single-nucleotide polymorphisms (SNPs) with small effect sizes. Although some
      phenotypes are hard to collect because of cost and loss to follow-up, correlated
      phenotypes that are easily collected can be leveraged for association analysis.
      In this paper, we evaluate a phenotype imputation method that incorporates family
      structure and correlation between multiple phenotypes using GAW20 simulated data.
      The distribution of missing values is derived using information contained in the
      missing sample's relatives and additional correlated phenotypes. We show that
      this imputation method can improve power in the association analysis compared
      with excluding observations with missing data, while achieving the correct Type I
      error rate. We also examine factors that may affect the imputation accuracy.

PMID- 30275900
TI  - Epigenome wide association study of SNP-CpG interactions on changes in
      triglyceride levels after pharmaceutical intervention: a GAW20 analysis.
AB  - In the search for an understanding of how genetic variation contributes to the
      heritability of common human disease, the potential role of epigenetic factors,
      such as methylation, is being explored with increasing frequency. Although
      standard analyses test for associations between methylation levels at individual
      cytosine-phosphate-guanine (CpG) sites and phenotypes of interest, some
      investigators have begun testing for methylation and how methylation may modulate
      the effects of genetic polymorphisms on phenotypes. In our analysis, we used both
      a genome-wide and candidate gene approach to investigate potential single
      nucleotide polymorphism (SNP)-CpG interactions on changes in triglyceride levels.
      Although we were able to identify numerous loci of interest when using an
      exploratory significance threshold, we did not identify any significant
      interactions using a strict genome-wide significance threshold. We were also able
      to identify numerous loci using the candidate gene approach, in which we focused
      on 18 genes with prior evidence of association of triglyceride levels. In
      particular, we identified GALNT2 loci as containing potential CpG sites that
      moderate the impact of genetic polymorphisms on triglyceride levels. Further work
      is needed to provide clear guidance on analytic strategies for testing SNP-CpG
      interactions, although leveraging prior biological understanding may be needed to
      improve statistical power in data sets with smaller sample sizes.

PMID- 30275901
TI  - Identification of epistatic interactions between the human RNA demethylases FTO
      and ALKBH5 with gene set enrichment analysis informed by differential
      methylation.
AB  - The Genetic Analysis Workshop (GAW) presents an opportunity to collaboratively
      evaluate methodology relevant to current issues in genetic epidemiology. The
      GAW20 data combine real clinical trial data with fictitious epigenetic drug
      response endpoints. Considering the evidence suggesting that networks of
      interactions between many genes underlie complex phenotypes, we utilize
      differential methylation status to identify a relevant gene set for enrichment
      analysis and use this to infer potential biological function underlying drug
      response. We highlight the pertinence of considering the potential for widespread
      epistatic interactions in the absence of main effects, and present evidence of
      epistasis between single-nucleotide polymorphisms (SNPs) on the two RNA
      demethylases FTO and ALKBH5.

PMID- 30275902
TI  - An adaptive gene-based test for methylation data.
AB  - DNA methylation plays an important role in normal human development and disease.
      In epigenome-wide association studies (EWAS), a univariate test for association
      between a phenotype and each cytosine-phosphate-guanine (CpG) site has been
      widely used. Given the number of CpG sites tested in EWAS, a stringent
      significance cutoff is required to adjust for multiple testing; in addition,
      multiple nearby CpG sites may be associated with the phenotype, which is ignored
      by a univariate test. These two factors may contribute to the power loss of a
      univariate test. As an alternative, we propose applying an adaptive gene-based
      test that is powerful in genome-wide association studies (GWAS), called aSPUw, to
      EWAS for simultaneous testing on multiple CpG sites within or near a gene. We
      show its application to the GAW20 methylation data set.

PMID- 30275903
TI  - Muscle Coordination Control for an Asymmetrically Antagonistic-Driven
      Musculoskeletal Robot Using Attractor Selection.
AB  - Recently, numerous musculoskeletal robots have been developed to realize the
      flexibility and dexterity analogous to human beings and animals. However, because
      the arrangement of many actuators is complex, the design of the control system
      for the robot is difficult and challenging. We believe that control methods
      inspired by living things are important in the development of the control systems
      for musculoskeletal robots. In this study, we propose a muscle coordination
      control method using attractor selection, a biologically inspired search method,
      for an antagonistic-driven musculoskeletal robot in which various muscles
      (monoarticular muscles and a polyarticular muscle) are arranged asymmetrically.
      First, muscle coordination control models for the musculoskeletal robot are built
      using virtual antagonistic muscle structures with a virtually symmetric muscle
      arrangement. Next, the attractor selection is applied to the control model and
      subsequently applied to the previous control model without muscle coordination to
      compare the control model's performance. Finally, position control experiments
      are conducted, and the effectiveness of the proposed muscle coordination control
      and the virtual antagonistic muscle structure is evaluated.

PMID- 30275904
TI  - Restriction-deficient mutants and marker-less genomic modification for metabolic
      engineering of the solvent producer Clostridium saccharobutylicum.
AB  - Background: Clostridium saccharobutylicum NCP 262 is a solventogenic bacterium
      that has been used for the industrial production of acetone, butanol, and
      ethanol. The lack of a genetic manipulation system for C. saccharobutylicum
      currently limits (i) the use of metabolic pathway engineering to improve the
      yield, titer, and productivity of n-butanol production by this microorganism, and
      (ii) functional genomics studies to better understand its physiology. Results: In
      this study, a marker-less deletion system was developed for C. saccharobutylicum
      using the codBA operon genes from Clostridium ljungdahlii as a counterselection
      marker. The codB gene encodes a cytosine permease, while codA encodes a cytosine
      deaminase that converts 5-fluorocytosine to 5-fluorouracil, which is toxic to the
      cell. To introduce a marker-less genomic modification, we constructed a suicide
      vector containing: the catP gene for thiamphenicol resistance; the codBA operon
      genes for counterselection; fused DNA segments both upstream and downstream of
      the chromosomal deletion target. This vector was introduced into C.
      saccharobutylicum by tri-parental conjugation. Single crossover integrants are
      selected on plates supplemented with thiamphenicol and colistin, and,
      subsequently, double-crossover mutants whose targeted chromosomal sequence has
      been deleted were identified by counterselection on plates containing 5
      fluorocytosine. Using this marker-less deletion system, we constructed the
      restriction-deficient mutant C. saccharobutylicum DeltahsdR1DeltahsdR2DeltahsdR3,
      which we named C. saccharobutylicum Ch2. This triple mutant exhibits high
      transformation efficiency with unmethylated DNA. To demonstrate its applicability
      to metabolic engineering, the method was first used to delete the xylB gene to
      study its role in xylose and arabinose metabolism. Furthermore, we also deleted
      the ptb and buk genes to create a butyrate metabolism-negative mutant of C.
      saccharobutylicum that produces n-butanol at high yield. Conclusions: The plasmid
      vectors and the method introduced here, together with the restriction-deficient
      strains described in this work, for the first time, allow for efficient marker
      less genomic modification of C. saccharobutylicum and, therefore, represent
      valuable tools for the genetic and metabolic engineering of this industrially
      important solvent-producing organism.

PMID- 30275905
TI  - Structural changes in lignocellulosic biomass during activation with ionic
      liquids comprising 3-methylimidazolium cations and carboxylate anions.
AB  - Background: Lignocellulosic biomass requires either pretreatment and/or
      fractionation to recover its individual components for further use as
      intermediate building blocks for producing fuels, chemicals, and products.
      Numerous ionic liquids (ILs) have been investigated for biomass pretreatment or
      fractionation due to their ability to activate lignocellulosic biomass, thereby
      reducing biomass recalcitrance with minimal impact on its structural components.
      In this work, we studied and compared 1-allyl-3-methylimidazolium formate
      ([AMIM][HCOO]) to the commonly used 1-ethyl-3-methylimidazolium acetate
      ([EMIM][CH3COO]) for its potential to activate hybrid poplar biomass and enable
      high cellulose and hemicellulose enzymatic conversion. Although [EMIM][CH3COO]
      has been widely used for activation, [AMIM][HCOO] was recently identified to
      achieve higher biomass solubility, with an increase of 40% over [EMIM][CH3COO].
      Results: Since IL activation is essentially an early stage of IL dissolution, we
      assessed the recalcitrance of [EMIM][CH3COO] and [AMIM][HCOO]-activated biomass
      through a suite of analytical tools. More specifically, Fourier transform
      infrared spectroscopy and X-ray diffraction showed that activation using
      [AMIM][HCOO] does not deacetylate hybrid poplar as readily as [EMIM][CH3COO] and
      preserves the crystallinity of the cellulose fraction, respectively. This was
      supported by scanning electron microscopy and enzymatic saccharification
      experiments in which [EMIM][CH3COO]-activated biomass yielded almost twice the
      cellulose and hemicellulose conversion as compared to [AMIM][HCOO]-activated
      biomass. Conclusion: We conclude that the IL [AMIM][HCOO] is better suited for
      biomass dissolution and direct product formation, whereas [EMIM][CH3COO] remains
      the better IL for biomass activation and fractionation.

PMID- 30275906
TI  - Rapid characterization of the activities of lignin-modifying enzymes based on
      nanostructure-initiator mass spectrometry (NIMS).
AB  - Background: Producing valuable fuels and chemicals from lignin is a key factor
      for making lignocellulosic biomass economically feasible; however, significant
      roadblocks exist due to our lack of detailed understanding of how lignin is
      enzymatically depolymerized and of the range of possible lignin fragments that
      can be produced. Development of suitable enzymatic assays for characterization of
      putative lignin active enzymes is an important step towards improving our
      understanding of the catalytic activities of relevant enzymes. Previously, we
      have successfully built an assay platform based on glycan substrates containing a
      charged perfluorinated tag and nanostructure-initiator mass spectrometry to study
      carbohydrate active enzymes, especially various glycosyl hydrolyses. Here, we
      extend this approach to develop a reliable and rapid assay to study lignin
      modifying enzymes. Results: Two beta-aryl ether bond containing model lignin
      dimer substrates, designed to be suitable for studying the activities of lignin
      modifying enzymes (LMEs) by nanostructure-initiator mass spectrometry (NIMS),
      were successful synthesized. Small-angle neutron scattering experiments showed
      that these substrates form micelles in solution. Two LMEs, laccase from the
      polypore mushroom Trametes versicolor, and manganese peroxidase (MnP) from white
      rot fungus Nematoloma frowardii, were tested for catalytic activity against the
      two model substrates. We show that the reaction of laccase and MnP with phenolic
      substrate yields products that arise from the cleavage of the carbon-carbon
      single bond between the alpha-carbon and the adjacent aryl carbon, consistent
      with the mechanism for producing phenoxy radical as reaction intermediates.
      Reactions of the nonphenolic substrate with laccase, on the other hand, adopt a
      different pathway by producing an alpha-oxidation product; as well as the
      cleavage of the beta-aryl ether bond. No cleavage of the carbon-carbon bond
      between the alpha-carbon and the aryl carbon was observed. To facilitate
      understanding of reaction kinetics, the reaction time course for laccase activity
      on the phenolic substrate (I) was generated by the simultaneous measurement of
      all products at different time points of the reaction. Withdrawal of only a small
      sample aliquot (0.2 MUL at each time point) ensured minimum perturbation of the
      reaction. The time course can help us to understand the enzyme kinetics.
      Conclusions: A new assay procedure has been developed for studying lignin
      modifying enzymes by nanostructure-initiator mass spectrometry. Enzyme assays of
      a laccase and a MnP on phenolic and nonphenolic beta-aryl ether substrates
      revealed different primary reaction pathways due to the availability of the
      phenoxy radical intermediates. Our assay provides a wealth of information on bond
      cleavage events not available using conventional colorimetric assays and can
      easily be carried out in microliter volumes and the quantitative analysis of
      product formation and kinetics is rapidly achieved by NIMS. This is the first
      time that NIMS technology was applied to study the activities of lignin-modifying
      enzymes. Unlike other previous works, our use of amphiphilic guaiacylglycerol
      beta-O-4 substrate (I) enables the formation of micelles. This approach helps
      avoid the re-polymerization of the resulting monomeric product. As a result, our
      assay can clearly demonstrate the degradation pathways of phenolic
      guaiacylglycerol beta-O-4 type of molecules with laccase and MnP.

PMID- 30275907
TI  - Enhancement of photosynthetic isobutanol production in engineered cells of
      Synechocystis PCC 6803.
AB  - Background: Cyanobacteria, oxygenic photoautotrophic prokaryotes, can be
      engineered to produce various valuable chemicals from solar energy and CO2 in
      direct processes. The concept of photosynthetic production of isobutanol, a
      promising chemical and drop-in biofuel, has so far been demonstrated for
      Synechocystis PCC 6803 and Synechococcus elongatus PCC 7942. In Synechocystis PCC
      6803, a heterologous expression of alpha-ketoisovalerate decarboxylase (Kivd)
      from Lactococcus lactis resulted in an isobutanol and 3-methyl-1-butanol
      producing strain. Kivd was identified as a bottleneck in the metabolic pathway
      and its activity was further improved by reducing the size of its substrate
      binding pocket with a single replacement of serine-286 to threonine (KivdS286T).
      However, isobutanol production still remained low. Results: In the present study,
      we report on how cultivation conditions significantly affect the isobutanol
      production in Synechocystis PCC 6803. A HCl-titrated culture grown under medium
      light (50 MUmol photons m-2 s-1) showed the highest isobutanol production with an
      in-flask titer of 194 mg l-1 after 10 days and 435 mg l-1 at day 40. This
      corresponds to a cumulative isobutanol production of 911 mg l-1, with a maximal
      production rate of 43.6 mg l-1 day-1 observed between days 4 and 6. Additional
      metabolic bottlenecks in the isobutanol biosynthesis pathway were further
      addressed. The expression level of KivdS286T was significantly affected when co
      expressed with another gene downstream in a single operon and in a convergent
      oriented operon. Moreover, the expression of the ADH encoded by codon-optimized
      slr1192 and co-expression of IlvC and IlvD were identified as potential
      approaches to further enhance isobutanol production in Synechocystis PCC 6803.
      Conclusion: The present study demonstrates the importance of a suitable
      cultivation condition to enhance isobutanol production in Synechocystis PCC 6803.
      Chemostat should be used to further increase both the total titer as well as the
      rate of production. Furthermore, identified bottleneck, Kivd, should be expressed
      at the highest level to further enhance isobutanol production.

PMID- 30275909
TI  - Complete genome sequence of Kocuria rhizophila BT304, isolated from the small
      intestine of castrated beef cattle.
AB  - Background: Members of the species Kocuria rhizophila, belonging to the family
      Micrococcaceae in the phylum Actinobacteria, have been isolated from a wide
      variety of natural sources, such as soil, freshwater, fish gut, and clinical
      specimens. K. rhizophila is important from an industrial viewpoint, because the
      bacterium grows rapidly with high cell density and exhibits robustness at various
      growth conditions. However, the bacterium is an opportunistic pathogen involved
      in human infections. Here, we sequenced and analyzed the genome of the K.
      rhizophila strain BT304, isolated from the small intestine of adult castrated
      beef cattle. Results: The genome of K. rhizophila BT304 consisted of a single
      circular chromosome of 2,763,150 bp with a GC content of 71.2%. The genome
      contained 2359 coding sequences, 51 tRNA genes, and 9 rRNA genes. Sequence
      annotations with the RAST server revealed many genes related to amino acid,
      carbohydrate, and protein metabolism. Moreover, the genome contained genes
      related to branched chain amino acid biosynthesis and degradation. Analysis of
      the OrthoANI values revealed that the genome has high similarity (> 97.8%) with
      other K. rhizophila strains, such as DC2201, FDAARGOS 302, and G2. Comparative
      genomic analysis further revealed that the antibiotic properties of K. rhizophila
      vary among the strains. Conclusion: The relatively small number of virulence
      related genes and the great potential in production of host available nutrients
      suggest potential application of the BT304 strain as a probiotic in breeding beef
      cattle.

PMID- 30275908
TI  - The prevalence of Campylobacter spp. in vegetables, fruits, and fresh produce: a
      systematic review and meta-analysis.
AB  - There are a number of reports indicating correlation between outbreaks of
      campylobacteriosis and the consumption of raw vegetables. This study is a meta
      analysis on the prevalence of Campylobacter in fresh vegetables and fruits
      without any location limitation, which was performed through a documented review
      of the available resources. Relevant literature was reviewed by trained
      reviewers, who examined the results for the inclusion of articles in the meta
      analysis. The prevalence of Campylobacter in raw vegetables, the sample source,
      the Campylobacter species, and the method of detection were extracted. The
      prevalence of Campylobacter in vegetables, fruits, and fresh produce were
      estimated to be 0.53%. Analysis of the various sample groups initially showed
      that the bean and sprouts group was the vegetable with the highest prevalence of
      Campylobacter (11.08%). The rate of contamination was higher when both the
      molecular and conventional methods were employed. The highest prevalence of
      Campylobacter was found in Asia (33.4%). Despite the low prevalence, consumption
      of raw vegetables is inherently risky because no treatment is used to inactivate
      the pathogens. Therefore, proper sanitation methods are recommended to treat the
      raw products.

PMID- 30275910
TI  - Effects of moderate intensity endurance training vs. high intensity interval
      training on weight gain, cardiorespiratory capacity, and metabolic profile in
      postnatal overfed rats.
AB  - Background: Obesity is associated with several comorbidities, such as
      cardiovascular disease and type 2 diabetes mellitus, and may have its origin in
      early life stages, such as in the lactation period, through metabolic
      programming. Physical activity aids in decreasing the chances of developing
      cardiovascular and metabolic diseases, even with small weight losses and, in
      children, can play an essential role in preventing weight gain and other health
      problems. The present study aimed to evaluate the effects of moderate intensity
      endurance training and high intensity interval training (HIIT) protocols on
      obesity-related parameters and cardiorespiratory capacity in overfed Wistar rats
      throughout the breastfeeding period. Methods: Two days after birth, forty male
      and female Wistar rats were clustered into two groups: Control Litter Group (CL;
      ten animals/litter) and Reduced Litter Group (RL; four animals/litter). At
      weaning, RL animals were distributed randomly into three experimental groups:
      sedentary, moderate intensity endurance training and HIIT, while CL animals were
      clustered into a sedentary group. Results: RL male and female body weight, before
      weaning, was significantly higher when compared with CL animals. This difference
      was maintained between CLSed and RLSed groups after weaning during all assessed
      periods. Adiposity was significantly higher in RLSed males when compared to CLSed
      males, and alterations in glycaemic metabolism were also observed. Endurance and
      HIIT protocols were efficient in improving maximal cardiorespiratory capacity, as
      well as concerning the glycemic metabolism and central fat accumulation of males
      and females submitted to childhood overfeeding by the litter reduction method.
      Conclusions: Both moderate endurance training and HIIT protocols included in
      early life were efficient in reverting or preventing certain metabolic
      alterations as a consequence of overfeeding during breastfeeding in male and
      female Wistar rats.

PMID- 30275911
TI  - Pancreatic fat deposition is increased and related to beta-cell function in women
      with familial partial lipodystrophy.
AB  - Background: To study pancreatic fat deposition and beta-cell function in familial
      partial lipodystrophy (FPLD) patients. Methods: In a cross-sectional study,
      eleven patients with FPLD, and eight healthy volunteers were matched for age and
      body mass index and studied at a referral center. Body composition was assessed
      using dual-energy X-ray absorptiometry and the Dixon method of magnetic resonance
      imaging was used to quantify pancreatic and liver fat. Fasting plasma glucose,
      insulin, leptin, lipids and homeostasis model assessment of insulin resistance
      values were measured, and an oral glucose tolerance test was performed. The
      insulinogenic index, Matsuda insulin sensitivity index and beta-cell disposition
      index were calculated. Results: The FPLD group presented a higher waist-to-hip
      ratio and fat mass ratio and lower total, truncal and lower-limb fat masses.
      Pancreatic and liver fat contents (log transformed) were significantly higher in
      the FPLD group (5.26 +/- 1.5 vs. 4.08 +/- 0.64, p = 0.034 and 0.77 +/- 0.50 vs.
      0.41 +/- 0.18, p = 0.056, respectively). Pancreatic fat was inversely related to
      the DI (r = - 0.53, p = 0.027) and HDL-cholesterol (r = - 0.63, p = 0.003) and
      directly related to WHR (r = 0.60; p = 0.009), HbA1c (r = 0.58; p = 0.01) and
      serum triglyceride (r = 0.48, p = 0.034). Higher triglyceride and lower HDL
      cholesterol levels were observed in the FPLD group. Conclusions: This study
      demonstrated for the first time that pancreatic fat deposition is increased in
      FPLD. Moreover, an inverse relationship was demonstrated between pancreatic fat
      and beta-cell function. The findings of this study may be consistent with the
      expandability hypothesis and the twin cycle hypothesis.

PMID- 30275912
TI  - Multiplexed microRNA Expression Profiling by Combined Asymmetric PCR and Label
      Free Detection using Silicon Photonic Sensor Arrays.
AB  - Analysis methods based upon the quantitative, real-time polymerase chain reaction
      are extremely powerful; however, they face intrinsic limitations in terms of
      target multiplexing. In contrast, silicon photonic microring resonators represent
      a modularly multiplexable sensor array technology that is well-suited to the
      analysis of targeted biomarker panels. In this manuscript we employ an asymmetric
      polymerase chain reaction approach to selectively amplify copies of cDNAs
      generated from targeted miRNAs before multiplexed, label-free quantitation
      through hybridization to microring resonator arrays pre-functionalized with
      capture sequences. This method, which shows applicability to low input amounts
      and a large dynamic range, was demonstrated for the simultaneous detection of
      eight microRNA targets from twenty primary brain tumor samples with expression
      profiles in good agreement with literature precedent.

PMID- 30275913
TI  - Bladder Cancer-Specific Nuclear Matrix Proteins-4 May Be a Potential Biomarker
      for Non-Muscle-Invasive Bladder Cancer Detection.
AB  - Aims: Bladder cancer-specific nuclear matrix protein-4 (BLCA-4) is a protein
      expressed mainly in bladder cancer tissues. Therefore, the aim of this study was
      to investigate its assisting diagnostic potential in non-muscle-invasive bladder
      cancer (NMIBC). Methods: Twenty patients with NMIBC, 20 with benign prostatic
      hyperplasia (BPH), and 20 normal controls were included in this study. Blood and
      urine samples were collected from all patients. Moreover, cancer foci and
      adjacent tissue samples were collected from NMIBC patients, and normal bladder
      tissue samples were collected from patients with BPH. A competitive enzyme-linked
      immunosorbent assay was used to determine the BLCA-4 level in serum and urine,
      and immunohistochemistry was used to examine BLCA-4 expression in bladder cancer,
      adjacent, and normal tissues. Results: Median urinary BLCA-4 levels in the NMIBC,
      BPH, and normal control groups were 0.759 ng/mL, 0.309 ng/mL, and 0.171 ng/mL,
      respectively. Urinary BLCA-4 level was significantly higher in the NMIBC group
      than in the other 2 groups (P < 0.01); meanwhile, the BPH group was higher than
      the normal control group (P < 0.05). Median serum BLCA-4 levels in the NMIBC,
      BPH, and normal control groups were 5.680 ng/mL, 5.928 ng/mL, and 5.473 ng/mL,
      respectively, showing no significant difference among groups (P > 0.05).
      Conclusion: As a new marker of bladder cancer, urinary BLCA-4 level detection
      might apply for clinical diagnosis or postoperative monitoring for NMIBC.

PMID- 30275914
TI  - Bimorph piezoelectric vibration energy harvester with flexible 3D meshed-core
      structure for low frequency vibration.
AB  - This paper proposes a bimorph piezoelectric vibration energy harvester (PVEH)
      with a flexible 3D meshed-core elastic layer for improving the output power while
      lowering the resonance frequency. Owing to the high void ratio of the 3D meshed
      core structure, the bending stiffness of the cantilever can be lowered. Thus, the
      deflection of the harvester and the strain in the piezoelectric layer increase.
      According to vibration tests, the resonance frequency is 15.8% lower and the
      output power is 68% higher than in the conventional solid-core PVEH. Compared to
      the solid-core PVEH, the proposed meshed-core PVEH (10 mm * 20 mm * 280 MUm) has
      1.3 times larger tip deflection and the maximum output power is 24.6 MUW under
      resonance condition at 18.7 Hz and 0.2G acceleration. Hence it can be used as a
      power supply for low-power-consumption sensor nodes in wireless sensor networks.

PMID- 30275915
TI  - Insights into photovoltaic properties of ternary organic solar cells from phase
      diagrams.
AB  - The efficiency of ternary organic solar cells relies on the spontaneous
      establishment of a nanostructured network of donor and acceptor phases during
      film formation. A fundamental understanding of phase composition and arrangement
      and correlations to photovoltaic device parameters is of utmost relevance for
      both science and technology. We demonstrate a general approach to understanding
      solar cell behavior from simple thermodynamic principles. For two ternary blend
      systems we construct and model phase diagrams. Details of EQE and solar cell
      parameters can be understood from the phase behavior. Our blend system is
      composed of PC70BM, PBDTTT-C and a near-infrared absorbing cyanine dye. Cyanine
      dyes are accompanied by counterions, which, in a first approximation, do not
      change the photophysical properties of the dye, but strongly influence the
      morphology of the ternary blend. We argue that counterion dissociation is
      responsible for different mixing behavior. For the dye with a hexafluorophosphate
      counterion a hierarchical morphology develops, the dye phase separates on a large
      scale from PC70BM and cannot contribute to photocurrent. Differently, a cyanine
      dye with a TRISPHAT counterion shows partial miscibility with PC70BM. A large two
      phase region dictated by the PC70BM: PBDTTT-C mixture is present and the dye
      greatly contributes to the short-circuit current.

PMID- 30275916
TI  - Serum Tumor Necrosis Factor-alpha and Interferon-gamma Levels in Pediatric
      Mycoplasma pneumoniae Pneumonia: A Systematic Review and Meta-Analysis.
AB  - Background: Mycoplasma pneumoniae pneumonia (MPP) is one of the most common forms
      of community-acquired pneumonia in children. The objective of this study was to
      explore potential changes in levels of serum tumor necrosis factor-alpha (TNF
      alpha) and interferon-gamma (IFN-gamma) associated with pediatric MPP. Methods:
      This protocol has been registered (PROSPERO 2017: CRD42017077979). A literature
      search was performed in October 2017 using PubMed, Embase, the Cochrane Library,
      and other Chinese medical databases to identify studies. The meta-analysis was
      performed using Review Manager 5.3 software. Random-effect models were used to
      estimate mean differences (MDs) and 95% confidence intervals (CIs) of cytokine
      levels. Results: Twelve studies were included in the meta-analysis, encompassing
      2,422 children with MPP and 454 healthy control children. Serum TNF-alpha levels
      were significantly higher in children with MPP compared with healthy children (MD
      = 22.5, 95% CI = 13.78-31.22, P < 0.00001), and there was significant
      heterogeneity across studies (I 2 = 100%, P < 0.00001). Subgroup analyses showed
      no evidence for a difference in serum TNF-alpha levels between children with
      refractory and nonrefractory MPP. Serum IFN-gamma levels did not significantly
      differ in children with MPP compared with healthy children (MD = 4.83, 95% CI = 
      3.27-12.93, P=0.24). Conclusions: Our meta-analysis showed that serum TNF-alpha
      and IFN-gamma levels were significantly elevated and unchanged, respectively, in
      pediatric MPP. Because infection by different pathogens has variable effects on
      serum TNF-alpha and IFN-gamma levels, the finding could be helpful in developing
      novel diagnostic methods.

PMID- 30275917
TI  - Helicobacter pylori Infection and Gastric Dysbiosis: Can Probiotics
      Administration Be Useful to Treat This Condition?
AB  - Helicobacter pylori (Hp) is responsible for one of the most common infections in
      the world. The prevalence exceeds 50% of the population in developing countries,
      and approximately one-third of the adults are colonized in North Europe and North
      America. It is considered a major pathogenic agent of chronic gastritis, peptic
      ulcer, atrophic gastritis, gastric cancer, and mucosa-associated lymphoid tissue
      lymphoma (MALT). Hp colonization modifies the composition of gastric microbiota
      that could drive the development of gastric disorders. Currently, an emerging
      problem in Hp treatment is represented by the increasing rate of antimicrobial
      therapy resistance. In this context, the search for adjuvant agents can be very
      useful to overcome this issue and probiotics administration can represent a valid
      option. The aim of this review is to describe the gastric microbiota changes
      during Hp colonization, the mechanisms of action, and a possible role of
      probiotics in the treatment of this infection.

PMID- 30275918
TI  - Pain Reconceptualisation after Pain Neurophysiology Education in Adults with
      Chronic Low Back Pain: A Qualitative Study.
AB  - Pain neurophysiology education (PNE) is an educational intervention for patients
      with chronic pain. PNE purports to assist patients to reconceptualise their pain
      away from the biomedical model towards a more biopsychosocial understanding by
      explaining pain biology. This study aimed to explore the extent, and nature, of
      patients' reconceptualisation of their chronic low back pain (CLBP) following
      PNE. Eleven adults with CLBP underwent semistructured interviews before and three
      weeks after receiving PNE. Interviews were transcribed verbatim and thematically
      analysed in a framework approach using four a priori themes identified from our
      previous research: (1) degrees of reconceptualisation, (2) personal relevance,
      (3) importance of prior beliefs, and (4) perceived benefit of PNE. We observed
      varying degrees of reconceptualisation from zero to almost complete, with most
      participants showing partial reconceptualisation. Personal relevance of the
      information to participants and their prior beliefs were associated with the
      degree of benefit they perceived from PNE. Where benefits were found, they
      manifested as improved understanding, coping, and function. Findings map closely
      to our previous studies in more disparate chronic pain groups. The phenomenon of
      reconceptualisation is applicable to CLBP and the sufficiency of the themes from
      our previous studies increases confidence in the certainty of the findings.

PMID- 30275920
TI  - Emergent embolization of a ruptured splenic artery aneurysm complicating Menkes
      disease.
AB  - We report a 7-year-old boy with Menkes disease complicated by rupture of a large
      splenic artery aneurysm. The aneurysm was successfully embolized with microcoils
      and n-butyl cyanoacrylate. Further angiographic evaluation revealed marked
      tortuosity of mesenteric and lower extremity vasculature, including the femoral
      arteries bilaterally, without aneurysm formation. The patient has since been
      evaluated annually with computed tomography angiography and there have been no
      additional vascular complications of his disease during 3-year follow up.

PMID- 30275919
TI  - Jaw Exercise Therapy and Psychoeducation to Reduce Oral Parafunctional Activities
      for the Management of Persistent Dentoalveolar Pain.
AB  - Objective: To retrospectively analyze the effects of our original combination
      therapy treatment on patients with nonodontogenic persistent dentoalveolar pain.
      Methods: Twenty-one patients suffering from persistent dentoalveolar pain
      (nineteen females and two males; mean age +/- standard deviation: 55.7 +/- 19.6
      years) participated in this study. They were treated with a therapy combination
      of jaw exercise and psychoeducation to reduce oral parafunctional activities
      every month. The intensity of pain in these subjects was evaluated using a
      numerical rating scale (NRS) before and after treatment. Results: The NRSs at the
      baseline ranged from 5 to 10 (median, 8), from 0 to 10 (median, 2) at one month
      after treatment, from 0 to 10 (median, 1) at three months after treatment, and
      from 0 to 10 (median, 0) at the end of treatment. Pain intensity after treatment
      improved significantly. Conclusion: There was a significant reduction in pain
      after our combination of therapies as nonpharmacological treatments, and
      therefore this treatment could be useful in the management of NPDP patients.

PMID- 30275921
TI  - Epipericardial fat necrosis: Uncommon cause of acute pleuritic chest pain.
AB  - Epipericardial fat necrosis (EPFN) is a rare cause for acute chest. We describe
      the case of a previously healthy 25-year-old man who presented with sudden onset
      of left-sided chest pain. Laboratory values showed only mildly elevated d-dimer
      and electrocardiogram was normal. However, subsequent CT angiogram of the chest
      revealed fat necrosis in the epipericardial fat, characteristic for EPFN, for
      which the patient was treated with nonsteroidal anti-inflammatory drug. This case
      highlights the importance of radiologists to consider the prospect of EPFN in the
      differential diagnosis of acute chest pain as correct diagnosis allows for
      conservative management and avoidance of more aggressive techniques in
      symptomatic patients.

PMID- 30275922
TI  - Primary lymphoma of the distal radius of a child: imaging features.
AB  - Primary lymphoma of bone (PLB) is a rare entity, defined as a lymphoma confined
      to the bone without evidence of systemic involvement. The disease commonly
      affects middle-aged to elderly population and it accounts for less than 1% of all
      malignant lymphomas. We present a case of a 10-year-old child affected by PLB of
      the forearm and the frontal bone. Characteristic imaging features of PLB and the
      main differential diagnosis were discussed.

PMID- 30275923
TI  - Endovascular retrieval of contraceptive implant embolized to pulmonary artery.
AB  - Embolization of subdermally implanted contraceptive devices is a rare but
      potentially serious event. Timely removal of the embolized foreign body should be
      considered to prevent possible hemodynamic, respiratory, or hormonal
      complications. We present a case of a 22-year-old woman with a contraceptive
      implant embolized to her right lower lobar pulmonary artery, which was
      successfully managed by endovascular retrieval.

PMID- 30275924
TI  - Brief Report: Competency-Based Supervision in Motivational Interviewing for
      Advanced Psychology Trainees: Targeting an A Priori Benchmark.
AB  - Motivational interviewing (MI) is an evidence based intervention with
      considerable support for promoting behavior change across a broad range of health
      and mental health issues. Despite its effectiveness, challenges associated with
      learning the approach may limit its full implementation in many clinical
      settings. The aim of the present study was to evaluate a supervised MI training
      practicum implemented within a doctoral internship/postdoctoral fellowship
      training Program. The goal of the practicum was to enable each trainee to achieve
      expert competence in MI. Participants were 29 psychology doctoral interns and 1
      postdoctoral fellow who participated in the training as part of their internship
      or fellowship program. Training included an initial workshop followed by a
      supervised practicum during which progress towards an a priori established expert
      competence benchmark was tracked through the use of an established coding system.
      Results indicated that trainees were satisfied with the supervision received.
      Three trainees did not achieve the a priori benchmark due to schedule conflicts.
      The 27 trainees who achieved the benchmark required between 4 and 20 supervision
      sessions to do so (mean = 9.22, SD = 3.77). With the exception of reflective
      listening skill, prior training, baseline skill, and self-reported motivation
      were not associated with number of supervision sessions required to achieve the
      benchmark. Implications for training and dissemination of MI in clinical settings
      are discussed.

PMID- 30275926
TI  - Corrigendum: Elderly woman with soft tissue ossification.
AB  - [This corrects the article DOI: 10.11604/pamj.2017.28.307.14507.].

PMID- 30275925
TI  - The Provision of Urban Ecosystem Services Throughout the Private-Social-Public
      Domain: A Conceptual Framework.
AB  - As cities are largely private systems, recent investigations have assessed the
      provision of ecosystem services from the private realm. However, these
      assessments are largely based on the concept of ownership and fail to capture the
      complexity of service provision mediated by interactions between people and
      ecological structures. In fact, people interact with ecological structures in
      their role of land tenants and stewards, further modulating the provision of
      ecosystem services. We devise a theoretical framework based on the concepts of
      ownership, tenancy, and stewardship, in which people, as mediators of ecosystem
      services, regulate the provision of services throughout the private-social-public
      domain. We survey relevant literature describing these dimensions and propose a
      comprehensive framework focused on the private-social-public domain. Our
      framework can advance ecosystem service research and enhance the provision of
      ecosystems services. The inclusion of people's individual, social and public
      roles in the mediation of ecosystem services could improve how benefits are
      planned for, prioritized, and optimized across cities.

PMID- 30275927
TI  - How well are aid agencies evaluating programs? An assessment of the quality of
      global health evaluations.
AB  - Evaluations are key to learning and accountability. We assessed the
      methodological quality of 37 randomly selected programme evaluations from 5 major
      global health funders. Two researchers rated each evaluation for relevance,
      validity, and reliability and met to resolve discrepancies. Most evaluations
      asked questions relevant to the health programme, but less than 40 per cent of
      impact evaluations and less than 10 per cent of performance evaluations used
      relevant data, followed accepted social science methods for sampling, or had high
      analytical validity and reliability. There is a need to improve the
      methodological quality of programme evaluations.

PMID- 30275928
TI  - First cytogenetic analysis of lesser gymnures (Mammalia, Galericidae, Hylomys)
      from Vietnam.
AB  - Gymnures are an ancient group of small insectivorous mammals and are
      characterized by a controversial taxonomic status and the lack of a description
      of karyotypes for certain species. In this study, conventional cytogenetic
      techniques (Giemsa, CBG- and GTG-banding, Ag-NOR), CMA3-DAPI staining, and
      fluorescent in situ hybridization (FISH) with telomeric DNA probes were used to
      examine for the first time the karyotypes of lesser gymnures of group
      Hylomyssuillus Muller, 1840 from northern and southern Vietnam. All studied
      specimens had karyotypes with 2n=48, NFa=64. C-positive heterochromatic blocks
      existed in centromeric regions of 7 bi-armed autosomes and the submetacentric X
      chromosome. The Y chromosome is a C-positive and dot-like. The nucleolus
      organizer regions resided terminally on the short arms of 2 small bi-armed pairs.
      Positive signals at the telomeres of all chromosomes were revealed by FISH. CMA3
      positive blocks were localized on the telomeric and pericentric regions of most
      bi-armed and acrocentric chromosomes. Despite the large genetic distances between
      Hylomys Muller, 1840, lesser gymnures from H.suillus-group from northern and
      southern Vietnam have similar karyotypic characteristics.

PMID- 30275929
TI  - Cytogenetic studies in three octopods, Octopusminor, Amphioctopusfangsiao, and
      Cistopuschinensis from the coast of China.
AB  - To provide markers to identify chromosomes in the genome of octopods, chromosomes
      of three octopus species were subjected to NOR/C-banding. In addition, we
      examined their genome size (C value) to submit it to the Animal Genome Size
      Database. Silver staining revealed that the number of Ag-nucleoli was 2
      (Octopusminor (Sasaki, 1920)), 2 (Amphioctopusfangsiao (d'Orbigny, 1839)) and 1
      (Cistopuschinensis Zheng et al., 2012), respectively, and the number of Ag
      nucleoli visible was the same as that of Ag-NORs on metaphase plates in the same
      species. In all analyzed metaphases, Ag-NORs were mainly located terminally on
      the long arms of chromosomes 3 (3rd) of O.minor and on the short arms of
      chromosomes 4 (4th) of A.fangsiao, whereas only one of the chromosomes 23 (23rd)
      was found Ag-NORs of C.chinensis. C-bands were localized predominantly in the
      centromeric regions of chromosomes in the three species, while other conspicuous
      stable C-bands were observed in terminal regions, including the Ag-NORs. That
      means these three chromosome pairs (3rd, 4th and 23rd) could be considered
      species-specific cytogenetic markers. The mean C values of O.minor, A.fangsiao
      and C.chinensis were 7.81+/-0.39 pg (0.070 pg per unit length), 8.31+/-0.18 pg
      (0.068 pg per unit length) and 5.29+/-0.10 pg (0.038 pg per unit length),
      respectively, and results showed that C values of the three species were not
      proportional to the relative length of the chromosomes. These cytogenetic
      characteristics will provide more theoretical foundation for further researches
      on chromosome evolution in octopods.

PMID- 30275930
TI  - New chromosome counts and genome size estimates for 28 species of Taraxacum sect.
      Taraxacum.
AB  - The species-rich and widespread genus Taraxacum F. H. Wiggers, 1780 (Asteraceae
      subfamily Cichorioideae) is one of the most taxonomically complex plant genera in
      the world, mainly due to its combination of different sexual and asexual
      reproduction strategies. Polyploidy is usually confined to apomictic
      microspecies, varying from 3x to 6x (rarely 10x). In this study, we focused on
      Taraxacum sect. Taraxacum (= T.sect.Ruderalia; T.officinale group), i.e., the
      largest group within the genus. We counted chromosome numbers and measured the
      DNA content for species sampled in Central Europe, mainly in Czechia. The
      chromosome number of the 28 species (T.aberrans Hagendijk, Soest & Zevenbergen,
      1974, T.atroviride Stepanek & Travnicek, 2008, T.atrox Kirschner & Stepanek,
      1997, T.baeckiiforme Sahlin, 1971, T.chrysophaenum Railonsala, 1957, T.coartatum
      G.E. Haglund, 1942, T.corynodes G.E. Haglund, 1943, T.crassum H. Ollgaard &
      Travnicek, 2003, T.deltoidifrons H. Ollgaard, 2003, T.diastematicum Marklund,
      1940, T.gesticulans H. Ollgaard, 1978, T.glossodon Sonck & H. Ollgaard, 1999,
      T.guttigestans H. Ollgaard in Kirschner & Stepanek, 1992, T.huelphersianum G.E.
      Haglund, 1935, T.ingens Palmgren, 1910, T.jugiferum H. Ollgaard, 2003,
      T.laticordatum Marklund, 1938, T.lojoense H. Lindberg, 1944 (= T.debrayi
      Hagendijk, Soest & Zevenbergen, 1972, T.lippertianum Sahlin, 1979), T.lucidifrons
      Travnicek, ineditus, T.obtusifrons Marklund, 1938, T.ochrochlorum G.E. Haglund,
      1942, T.ohlsenii G.E. Haglund, 1936, T.perdubium Travnicek, ineditus,
      T.praestabile Railonsala, 1962, T.sepulcrilobum Travnicek, ineditus, T.sertatum
      Kirschner, H. Ollgaard & Stepanek, 1997, T.subhuelphersianum M.P. Christiansen,
      1971, T.valens Marklund, 1938) is 2n = 3x = 24. The DNA content ranged from 2C =
      2.60 pg (T.atrox) to 2C = 2.86 pg (T.perdubium), with an average value of 2C =
      2.72 pg. Chromosome numbers are reported for the first time for 26 species (all
      but T.diastematicum and T.obtusifrons), and genome size estimates for 26 species
      are now published for the first time.

PMID- 30275931
TI  - Nanoscale inhibition of polymorphic and ambidextrous IAPP amyloid aggregation
      with small molecules.
AB  - Understanding how small molecules interface amyloid fibrils on the nanoscale is
      of importance for developing therapeutic treatment against amyloid-based
      diseases. Here we show, for the first time, that human islet amyloid polypeptide
      (IAPP) in the fibrillar form is polymorphic and ambidextrous possessing multiple
      periodicities. Upon interfacing with small molecule epigallocatechin gallate
      (EGCG), IAPP aggregation was rendered off pathway assuming the form of soft and
      disordered clusters, while mature IAPP fibrils displayed kinks and branching but
      conserved the twisted fibril morphology. These nanoscale phenomena resulted from
      competitive interactions between EGCG and the IAPP amyloidogenic region, as well
      as end capping of the fibrils by the small molecule. This information is crucial
      to delineating IAPP toxicity implicated in type 2 diabetes and developing new
      inhibitors against amyloidogenesis.

PMID- 30275932
TI  - Perceived control and avoidance in posttraumatic stress.
AB  - Despite much evidence concerning the importance of control over stressors in
      animal models of adaptation to stress, there is a dearth of experimental evidence
      for the role of controllability in posttraumatic stress disorder (PTSD). This
      study investigated whether perceived control over aversive stimuli influenced
      subsequent avoidance in a female community sample with and without PTSD
      symptomatology. Female participants (N = 145) with high or low PTSD symptoms were
      randomized to receive instructions indicating either controllable or
      uncontrollable offset of aversive, positive, and neutral images; despite this
      perception, the actual duration of presentations was standardized in both
      conditions. Participants subsequently completed an emotional avoidance task.
      There was a significant group * condition interaction effect, such that those
      with PTSD symptoms who were told they lacked control displayed greater avoidance
      of the subsequent stressor relative to those told they had control. This pattern
      was not observed in those without PTSD symptoms. This finding suggests that
      ongoing experiences of uncontrollability may heighten psychological
      vulnerabilities implicated in PTSD.

PMID- 30275933
TI  - Memory for neutral, emotional and trauma-related information in sexual abuse
      survivors.
AB  - Previous studies have shown that trauma-exposed individuals, including survivors
      of sexual abuse, show inferior performance in episodic memory tasks compared to
      non-exposed controls. This, however, has mainly been tested using neutral
      content. Our goal in this study was to determine whether this relative impairment
      in episodic memory extends to generally emotional and trauma-related content.
      Twenty-seven sexual abuse survivors and 27 control women participated in the
      study. They listened to stories with three content types (neutral, generally
      emotional and trauma-related) and performed a free-recall task immediately and 30
      minutes later. Sexual abuse survivors showed poorer recall of neutral material
      compared to control participants. Lower recall was also observed for generally
      emotional content. However, importantly, there was no difference between groups
      in the recall of trauma-related content. The main novel contribution of this
      study is the demonstration that verbal episodic memory is not impaired for non
      autobiographical trauma-related content in sexual abuse survivors. We discuss how
      this could be explained by personal relevance and attentional capture.

PMID- 30275934
TI  - A programme for the prevention of post-traumatic stress disorder in midwifery
      (POPPY): indications of effectiveness from a feasibility study.
AB  - Background: Midwives can experience events they perceive as traumatic when
      providingcare. As a result, some will develop post-traumatic stress disorder
      (PTSD), with adverse implications for their mental health, the quality of care
      provided for women and the employing organizations. POPPY (Programme for the
      prevention of PTSD in midwifery) is a package of educational and supportive
      resources comprising an educational workshop, information leaflet, peer support
      and access to trauma-focused clinical psychology intervention. A feasibility
      study of POPPY implementation was completed. Objective: This study aimed to
      identify potential impacts of POPPY on midwives' understandingof trauma, their
      psychological well-being and job satisfaction. Method: POPPY was implemented in
      one hospital site. Before taking part in the POPPY workshop (T1) midwives (N =
      153) completed self-report questionnaires, which measured exposure to work
      related trauma, knowledge and confidence of managing trauma responses,
      professional impacts, symptoms of PTSD, burnout and job satisfaction. Measures
      were repeated (T2) approximately 6 months after training (n = 91, 62%). Results:
      Midwives' confidence in recognizing (p = .001) and managing early traumaresponses
      in themselves and their colleagues significantly improved (both p < .001). There
      was a trend towards reduced levels of PTSD symptomatology, and fewer midwives
      reported sub clinical levels of PTSD (from 10% at T1 to 7% at T2). The proportion
      of midwives reporting high and moderate levels of depersonalization towards care
      was reduced (33% to 20%) and midwives reported significantly higher levels of job
      satisfaction at T2 (p < .001). Reductions in self-reported stress-related
      absenteeism (12% to 5%), long-term changes to clinical allocation (10% to 5%) and
      considerations about leaving midwifery (34% to 27%) were identified. Conclusions:
      In conclusion, POPPY  shows very positive potential to improve midwives' mental
      health and the sensitivity of care they provide, and reduce service disruption
      and costs for trusts. Large-scale longitudinal evaluation is required.

PMID- 30275936
TI  - Machine Learning Methods for Histopathological Image Analysis.
AB  - Abundant accumulation of digital histopathological images has led to the
      increased demand for their analysis, such as computer-aided diagnosis using
      machine learning techniques. However, digital pathological images and related
      tasks have some issues to be considered. In this mini-review, we introduce the
      application of digital pathological image analysis using machine learning
      algorithms, address some problems specific to such analysis, and propose possible
      solutions.

PMID- 30275935
TI  - FoldX as Protein Engineering Tool: Better Than Random Based Approaches?
AB  - Improving protein stability is an important goal for basic research as well as
      for clinical and industrial applications but no commonly accepted and widely used
      strategy for efficient engineering is known. Beside random approaches like error
      prone PCR or physical techniques to stabilize proteins, e.g. by immobilization,
      in silico approaches are gaining more attention to apply target-oriented
      mutagenesis. In this review different algorithms for the prediction of beneficial
      mutation sites to enhance protein stability are summarized and the advantages and
      disadvantages of FoldX are highlighted. The question whether the prediction of
      mutation sites by the algorithm FoldX is more accurate than random based
      approaches is addressed.

PMID- 30275937
TI  - A Review of Matched-pairs Feature Selection Methods for Gene Expression Data
      Analysis.
AB  - With the rapid accumulation of gene expression data from various technologies,
      e.g., microarray, RNA-sequencing (RNA-seq), and single-cell RNA-seq, it is
      necessary to carry out dimensional reduction and feature (signature genes)
      selection in support of making sense out of such high dimensional data. These
      computational methods significantly facilitate further data analysis and
      interpretation, such as gene function enrichment analysis, cancer biomarker
      detection, and drug targeting identification in precision medicine. Although
      numerous methods have been developed for feature selection in bioinformatics, it
      is still a challenge to choose the appropriate methods for a specific problem and
      seek for the most reasonable ranking features. Meanwhile, the paired gene
      expression data under matched case-control design (MCCD) is becoming increasingly
      popular, which has often been used in multi-omics integration studies and may
      increase feature selection efficiency by offsetting similar distributions of
      confounding features. The appropriate feature selection methods specifically
      designed for the paired data, which is named as matched-pairs feature selection
      (MPFS), however, have not been maturely developed in parallel. In this review, we
      compare the performance of 10 feature-selection methods (eight MPFS methods and
      two traditional unpaired methods) on two real datasets by applied three
      classification methods, and analyze the algorithm complexity of these methods
      through the running of their programs. This review aims to induce and
      comprehensively present the MPFS in such a way that readers can easily understand
      its characteristics and get a clue in selecting the appropriate methods for their
      analyses.

PMID- 30275938
TI  - Engineering mesenchymal stem cells to improve their exosome efficacy and yield
      for cell-free therapy.
AB  - Through traditional medicine, there were diseases and disorders that previously
      remained untreated or were simply thought to be incurable. Since the discovery of
      mesenchymal stem cells (MSCs), there has been a flurry of research to develop MSC
      based therapy for diseases and disorders. It is now well-known that MSCs do not
      typically engraft after transplantation and exhibit their therapeutic effect via
      a paracrine mechanism. In addition to secretory proteins, MSCs also produce
      extracellular vesicles (EVs), membrane-bound nanovesicles containing proteins,
      DNA and RNA. The secreted vesicles then interact with target cells and deliver
      their contents, imparting their ultimate therapeutic effect. Unlike the widely
      studied cancer cells, the yield of MSC-exosomes is a limiting factor for large
      scale production for cell-free therapies. Here we summarise potential approaches
      to increase the yield of such vesicles while maintaining or enhancing their
      efficacy by engineering the extracellular environment and intracellular
      components of MSCs.

PMID- 30275940
TI  - Breaking bad news protocol for cancer disclosure: an Iranian version.
AB  - In Iran, as in many Asian and Middle Eastern countries, a significant proportion
      of cancer patients are never informed of their illness. One solution that has
      been proposed to tackle this challenge is to develop a localized protocol on
      cancer diagnosis disclosure based on the culture and values of community members,
      and train healthcare team members to deliver the bad news using this protocol.
      This article introduces a localized protocol for disclosure of bad news to cancer
      patients in Iran. This protocol consists of six steps, including assessment,
      planning, preparation, disclosure, support and conclusion. In the drafting of
      this protocol an attempt was made to meticulously consider the cultural features
      of the Iranian society. Although breaking bad news will never be easy, having an
      appropriate plan of action based on individual's attitudes, considerably helps
      health-care professionals, and provides more satisfaction in patients.

PMID- 30275939
TI  - Health related quality of life in patients having schizophrenia negative symptoms
      - a systematic review.
AB  - Background: Schizophrenia negative symptoms (SNS) contribute substantially to
      poor functional outcomes, loss in productivity and poor quality of life. It is
      unclear which instruments may be used for assessing quality of life in patients
      with SNS. Objective: The objective of this review was to identify instruments
      assessing health-related quality of life (HRQoL) validated in patients with SNS
      and to assess their level of validation. Data sources: We conducted a systematic
      literature review in Medline and the ISPOR database in March 2016 to identify
      studies on the quality of life in patients with SNS published by March 2016. Data
      extraction: Psychometric properties and validation steps. Data synthesis: After
      applying inclusion/exclusion criteria, 49 studies were selected for the analysis
      of HRQoL instruments; however, none of these instruments only addressed patients
      with SNS. Of these, 19 HRQoL instruments used in patients with schizophrenia or
      including patients with SNS among others, in the context of instrument
      validation, were identified (4 generic, 10 non-specific mental health, 5
      schizophrenia-specific). Conclusion: No HRQoL instrument has been validated in
      patients with SNS only; for the remaining instruments identified, it remains
      unclear whether they were intended to capture HRQoL in patients with SNS.

PMID- 30275941
TI  - Bilateral glomus tympanicum tumors: Human temporalbone study.
AB  - To describe human temporal bones with bilateral glomus tympanicum tumors. Patient
      is 83-year-old black female who no pulsatile tinnitus. The histopathologic
      characteristics of human temporal bones after death were setting Department of
      Otolaryngology of University of Minnesota in USA. Histopathologic observation of
      temporal bones showed bilateral small glomus tympanicum tumors limited to the
      promontory. Although there was bilateral tinnitus, there was no pulsatile
      tinnitus, no conductive hearing loss and both of the tympanic membranes were
      intact. Histopathologic observation of temporal bones after death showed
      bilateral glomus tympanicum tumors. To our knowledge, this is the first reported
      case of bilateral glomus tympanicum tumors.

PMID- 30275942
TI  - SYNE1-related autosomal recessive cerebellar ataxia, congenital cerebellar
      hypoplasia, and cognitive impairment.
AB  - The spectrin repeat-containing nuclear envelope protein 1 (SYNE1) gene encodes a
      family of spectrin structural proteins that are associated with anchoring the
      plasma membrane to the actin cytoskeleton. SYNE1-related disease is most commonly
      reported in autosomal recessive spinocerebellar ataxia 8, which demonstrates
      variable age of onset with a median of 30 years of age. However pathogenic
      mutations in SYNE1 are also causative of arthrogryposis multiplex congenital, a
      severe congenital neuromuscular condition. Here in we report monozygous twins
      with childhood onset ataxia, cerebellar hypoplasia, dysarthria, and cognitive
      impairment sharing two novel heterozygous mutations in the SYNE1 gene. Our family
      may expand the clinical phenotype associated with SYNE1-related disease and
      offers possible genotype-phenotype correlations of a rare continuum of clinical
      disease phenotypes from neonatal to adult onset.

PMID- 30275943
TI  - The Role of the Pupil, Corneal Reflex, and Iris in Determining the Perceived
      Direction of Gaze.
AB  - In specially constructed movies depicting moving eyes, the pupils, irises, and
      corneal reflexes moved independently and sometimes in opposite directions. We
      found that the moving pupils or the corneal reflex, not the moving irises,
      determined the perceived direction of gaze (online Movie 1). When the pupils and
      irises moved in opposite directions, the one with the higher Michelson contrast
      determined the perceived direction of gaze (online Movie 2).

PMID- 30275945
TI  - Incidence and outcomes of multidrug-resistant gram-negative bacteria infections
      in intensive care unit from Nepal- a prospective cohort study.
AB  - Background: Infections caused by multi-drug resistant gram-negative bacterial
      infections are the principle threats to the critically ill patients of intensive
      care units. Increasing reports of these infections from the Nepalese intensive
      care unit underline the clinical importance of these pathogens. However, the
      impact of these infections on the patient's clinical outcome has not yet been
      clearly evaluated. The objective of our study was to determine the incidence and
      associated clinical outcome of multi-drug resistant gram-negative bacterial
      infections in intensive care unit from a tertiary care center of Nepal. Methods:
      A prospective cohort study was conducted among adult patients admitted in
      intensive care unit of B. P Koirala Institute of Health Sciences from July to
      December 2017. Patients infected with multi-drug resistant gram-negative
      bacteria, non-multi-drug resistant gram-negative bacteria and those without
      infection were included. Identification of gram-negative bacteria and their
      antibiotic susceptibility pattern was performed with standard microbiological
      methods. Demographic, clinical profiles and outcomes (in-hospital-mortality,
      intensive care unit and hospital length of stay) were documented. Results: The
      incidence rate of multi-drug resistant gram-negative bacteria infections was 47
      per 100 admitted patients (64/137) with 128 episodes. Acinetobacter species (41%,
      52/128) was the commonest followed by Klebsiella pneumoniae (28%, 36/128) and
      Pseudomonas spp (21%, 27/128). Patients with multi-drug resistant gram-negative
      bacteria in comparison to non-multi-drug resistant gram-negative bacteria had
      high healthcare-associated infections (95%, 61/64 versus 20%, 2/10; p = < 0.001).
      In-hospital-mortality was 38% (24/64), 20% (2/10) and 10% (4/41) in multi-drug
      resistant, non-multi-drug resistant and uninfected group respectively (p =
      0.007). After adjustment for independent risk factors, compared to uninfected
      patients, the odds ratio (CI) for in-hospital-mortality in multi-drug resistant
      and non-multi-drug resistant group was (4.7[1.4-15.5], p = 0.01) and 2.60 [0.38
      17.8], p = 0.32) respectively. Multi-drug resistant patients also had longer
      intensive care unit and hospital stay, however, it was statistically
      insignificant. Conclusion: The incidence of multi-drug resistant gram-negative
      bacterial infections was remarkably high in our intensive care unit and showed a
      significant association with healthcare-associated infections and in-hospital
      mortality.

PMID- 30275944
TI  - Deep analysis of immune response and metabolic signature in children with food
      protein induced enterocolitis to cow's milk.
AB  - Background: Food Protein-Induced Enterocolitis Syndrome (FPIES) is considered to
      be a non-IgE mediated food allergy. However, its pathogenesis remains poorly
      understood and biomarkers are lacking. We aimed to perform in-depth
      characterization of humoral and cellular immune responses in children with cow's
      milk (CM)-FPIES and investigated whether there is a FPIES metabolomic signature.
      Methods: Children with CM-FPIES and control subjects with an IgE-mediated CM
      allergy (IgE-CMA), both avoiding CM, were recruited on the day of an oral food
      challenge. Blood samples were collected before the challenge. Total and specific
      levels of IgE, IgG1-4, IgA, IgM and IgD to various whey and casein allergens and
      to their gastroduodenal digestion products were measured in plasma, using plasma
      from CM-tolerant peanut allergic patients (IgE-PA, not avoiding CM) as additional
      controls. Cytokine secretion and cellular proliferation were analyzed after
      stimulation of PBMC with different CM allergens. Metabolomic profiles were
      obtained for plasma samples using liquid chromatography coupled to high
      resolution mass spectrometry. Results: Nine children with CM-FPIES and 12 control
      subjects (6 IgE-CMA and 6 IgE-PA) were included. In children with CM-FPIES, total
      Ig concentrations were lower than in control subjects, specific Ig against CM
      components were weak to undetectable, and no specific IgE against CM digestion
      products were detected. Moreover, in CM-FPIES patients, we did not find any Th
      cell proliferation or associated cytokine secretion after allergen reactivation,
      whereas such responses were clearly found in children with IgE-CMA. Plasma
      metabolic profiles were different between CM allergic patients, with
      significantly lower concentrations of various fatty acids and higher
      concentrations of primary metabolites such as amino acids in CM-FPIES compared to
      IgE-CMA patients. Conclusions: In CM-FPIES, both humoral and cellular specific
      immune responses are weak or absent, and this is not related to CM avoidance. A
      metabolomic signature was identified in patients with CM-FPIES that may be useful
      for the diagnosis and management of this disease.

PMID- 30275946
TI  - Wireless whispering-gallery-mode sensor for thermal sensing and aerial mapping.
AB  - The Internet of Things (IoT)1,2 employs a large number of spatially distributed
      wireless sensors to monitor physical environments, e.g., temperature, humidity,
      and air pressure, and has many applications, including environmental monitoring3,
      health care monitoring4, smart cities5, and precision agriculture. A wireless
      sensor can collect, analyze, and transmit measurements of its environment1,2.
      Currently, wireless sensors used in the IoT are predominately based on electronic
      devices that may suffer from electromagnetic interference in many circumstances.
      Being immune to the electromagnetic interference, optical sensors provide a
      significant advantage in harsh environments6. Furthermore, by introducing optical
      resonance to enhance light-matter interactions, optical sensors based on
      resonators exhibit small footprints, extreme sensitivity, and versatile
      functionalities7,8, which can significantly enhance the capability and
      flexibility of wireless sensors. Here we provide the first demonstration of a
      wireless photonic sensor node based on a whispering-gallery-mode (WGM) optical
      resonator, in which light propagates along the circular rim of such a structure
      like a sphere, a disk, or a toroid by continuous total internal reflection. The
      sensor node is controlled via a customized iOS app. Its performance was studied
      in two practical scenarios: (1) real-time measurement of the air temperature over
      12 h and (2) aerial mapping of the temperature distribution using a sensor node
      mounted on an unmanned drone. Our work demonstrates the capability of WGM optical
      sensors in practical applications and may pave the way for the large-scale
      deployment of WGM sensors in the IoT.

PMID- 30275947
TI  - Optical conductivity-based ultrasensitive mid-infrared biosensing on a hybrid
      metasurface.
AB  - Optical devices are highly attractive for biosensing as they can not only enable
      quantitative measurements of analytes but also provide information on molecular
      structures. Unfortunately, typical refractive index-based optical sensors do not
      have sufficient sensitivity to probe the binding of low-molecular-weight
      analytes. Non-optical devices such as field-effect transistors can be more
      sensitive but do not offer some of the significant features of optical devices,
      particularly molecular fingerprinting. We present optical conductivity-based mid
      infrared (mid-IR) biosensors that allow for sensitive and quantitative
      measurements of low-molecular-weight analytes as well as the enhancement of
      spectral fingerprints. The sensors employ a hybrid metasurface consisting of
      monolayer graphene and metallic nano-antennas and combine individual advantages
      of plasmonic, electronic and spectroscopic approaches. First, the hybrid
      metasurface sensors can optically detect target molecule-induced carrier doping
      to graphene, allowing highly sensitive detection of low-molecular-weight analytes
      despite their small sizes. Second, the resonance shifts caused by changes in
      graphene optical conductivity is a well-defined function of graphene carrier
      density, thereby allowing for quantification of the binding of molecules. Third,
      the sensor performance is highly stable and consistent thanks to its
      insensitivity to graphene carrier mobility degradation. Finally, the sensors can
      also act as substrates for surface-enhanced infrared spectroscopy. We
      demonstrated the measurement of monolayers of sub-nanometer-sized molecules or
      particles and affinity binding-based quantitative detection of glucose down to
      200 pM (36 pg/mL). We also demonstrated enhanced fingerprinting of minute
      quantities of glucose and polymer molecules.

PMID- 30275948
TI  - Nutrition and listeriosis during pregnancy: a systematic review.
AB  - Listeriosis is a rare but severe foodborne illness which is more common in
      populations such as pregnant women, and can result in serious complications
      including miscarriage, prematurity, maternal and neonatal sepsis, and death in
      the newborn. Population recommendations exist for specific foods and food
      preparation practices to reduce listeriosis risk during pregnancy. The aim of the
      present systematic review was to assess the association between listeriosis and
      these practices during pregnancy to confirm appropriateness of these
      recommendations. We searched MEDLINE, Embase, CINAHL Plus, Web of Science Core
      Collection, included articles' references, and contacted clinical experts. All
      databases were searched until July 2017. Case-control and cohort studies were
      included which assessed pregnant women or their newborn offspring with known
      listeriosis status and a nutritional exposure consistent with international
      population recommendations for minimising listeriosis. Outcomes included
      listeriosis with or without pregnancy outcomes. Risk of bias was assessed through
      the Newcastle-Ottawa Scale. Results were described narratively due to clinical
      heterogeneity in differences in nutritional exposures. Eleven articles comprising
      case-control or cross-sectional studies met the inclusion criteria. Cases of
      maternal, fetal or neonate listeriosis were more likely to have consumed high
      risk dairy products, meat products or some fruits during pregnancy in comparison
      with women without listeriosis. Cases of listeriosis were more likely to have
      consumed foods that are highlighted in population guidelines to avoid to minimise
      listeriosis in comparison with those without listeriosis during pregnancy.
      Further research is warranted assessing means of improving the reach, uptake and
      generalisability of population guidelines for reducing listeriosis during
      pregnancy.

PMID- 30275949
TI  - Laparoscopic Roux-en-Y gastric bypass is as safe as laparoscopic sleeve
      gastrectomy. Results of a comparative cohort study.
AB  - Background: A meta-analysis and six randomized controlled trials show higher 30
      day complication rates with laparoscopic Roux-en-Y gastric bypass (LRYGB) than
      with laparoscopic sleeve gastrectomy (LSG). Aim: To identify any difference in 30
      day outcomes of patients treated with LRYGB or LSG when a standardized technique
      and identical post-operative protocol was followed with all procedures being
      conducted either by or under the supervision of a single consultant surgeon who
      had significant experience in bariatric surgery prior to commencing independent
      practice. Methods: A prospectively collected database of all patients under
      primary LRYGB or LSG, between March 2010 and February 2017, was analyzed. Data on
      demographics, length-of-stay (LOS), conversion to open, 30-day complications and
      mortality were reviewed. Results: Over a seven-year period, 485 patients (LRYGB
      279 and LSG-206) were included. There were no significant demographic differences
      and no difference in the pre-operative risk scoring [American Society of
      Anesthesiologists (ASA) and obesity surgery mortality risk score (OSMRS)] between
      the groups. There was no significant difference between the groups in terms of
      LOS (p = 0.275), complications (p = 0.920), re-admissions (p = 0.593) or re
      operations (p = 0.366) within 30-days. There were no conversions to open or in
      patient mortality in either group. Conclusions: Unlike previous studies, we found
      no difference in early complication rates between LRYGB and LSG in a comparable
      cohort when performed by a surgeon with sufficient experience in bariatric
      surgery.

PMID- 30275950
TI  - Protein interaction and functional data indicate MTHFD2 involvement in RNA
      processing and translation.
AB  - Background: The folate-coupled metabolic enzyme MTHFD2 is overexpressed in many
      tumor types and required for cancer cell proliferation, and is therefore of
      interest as a potential cancer therapeutic target. However, recent evidence
      suggests that MTHFD2 has a non-enzymatic function which may underlie the
      dependence of cancer cells on this protein. Understanding this non-enzymatic
      function is important for optimal targeting of MTHFD2 in cancer. Methods: To
      identify potential non-enzymatic functions of MTHFD2, we defined its interacting
      proteins using co-immunoprecipitation and mass spectrometry and integrated this
      information with large-scale co-expression analysis, protein dynamics, and gene
      expression response to MTHFD2 knockdown. Results: We found that MTHFD2 physically
      interacts with a set of nuclear proteins involved in RNA metabolism and
      translation, including components of the small ribosomal subunit and multiple
      members of the RNA-processing hnRNP family. Interacting proteins were also in
      general co-expressed with MTHFD2 in experiments that stimulate or repress
      proliferation, suggesting a close functional relationship. Also, unlike other
      folate one-carbon enzymes, the MTHFD2 protein has a short half-life and responds
      rapidly to serum. Finally, shRNA against MTHFD2 depletes several of its
      interactors and yields an overall transcriptional response similar to targeted
      inhibition of certain ribosomal subunits. Conclusions: Taken together, our
      findings suggest a novel function of MTHFD2 in RNA metabolism and translation.

PMID- 30275951
TI  - Predictors of mortality among under-five children with severe acute malnutrition,
      Northwest Ethiopia: an institution based retrospective cohort study.
AB  - Background: Globally, approximately 19 million children under 5 years are
      suffering from Severe Acute Malnutrition (SAM). It is a major cause of morbidity
      and mortality in low-income countries including Ethiopia. However, little is
      known regarding predictors of mortality among these children in Ethiopia. The
      current study aimed to assess the potential predictors of mortality among under
      five children with SAM admitted to a stabilization center. Method: A
      retrospective cohort study was conducted in 527 under-five children who were
      admitted for SAM at the University of Gondar comprehensive specialized hospital
      from 2014 to 2016. Data were collected from a randomly selected chart after
      getting ethical clearance. Data were cleaned, coded and entered to Epi-info
      (version 7) and analyzed using STATA (version14). The outcome was computed by
      using tables and graphs. A multivariable cox proportional hazards model was
      fitted to identify predictors of mortality. Result: Overall, the median follow-up
      period was 10 days with interquartile range (Q1, Q3: 8, 17). At the end of the
      follow-up, the mortality rate was 66(12.52%). Anemia (AHR(Adjusted Hazard Ratio):
      2.3, 95% CI: 1.2, 4.5), Shock (AHR: 7.9, 95% CI: 3.7, 16.7), no intake of
      antibiotics (AHR: 2.3 95% CI: 1.2, 4.4), IV-Fluid (AHR: 3.2, 95% CI: 1.7, 5.8),
      no intake of F75 (AHR: 6.6,95% CI: 2.9, 14.7) and no intake of F100 (AHR: 3, 95%
      CI: 1.6, 5.4) were independent predictors of mortality. Conclusion: The survival
      status of under-five children with SAM was lower than the national standard
      protocol. Altered general conditions such as shock, anemia, not adhering to
      medical and nutritional therapies were identified as predictors of mortality
      among SAM children. Health education on early medical seeking behavior and
      adherence on the routine regimens may improve this gap in child survival.

PMID- 30275953
TI  - Effective combined therapy with ramucirumab for advanced pulmonary pleomorphic
      carcinoma.
AB  - Pulmonary pleomorphic carcinoma (PPC) is a rare disease with a poor prognosis.
      Most patients with PPC are refractory to chemotherapy, whereas good responses to
      platinum-based chemotherapy in combination with the anti-angiogenesis agent
      bevacizumab have been reported. An 82-year-old man was diagnosed with PPC with a
      clinical stage of T3N0M0, coincident with primary lung adenocarcinoma in an early
      stage. We chose single-agent chemotherapy with docetaxel as an initial treatment,
      but both the primary adenocarcinoma and two PPC lesions in the right lung were
      enlarged after one treatment cycle. We subsequently started treatment with
      ramucirumab and docetaxel, and thereafter, the disease showed a good partial
      response. Here, we report the first case of advanced PPC that was effectively
      treated with chemotherapy and the anti-VEGFR-2 antibody ramucirumab. These
      observations suggest a potential therapeutic strategy for patients with PPC.

PMID- 30275952
TI  - SRSF2 mutations in myelodysplasia/myeloproliferative neoplasms.
AB  - Recurrent gene mutations have been described with varying frequencies in
      myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndromes (MMOS).
      Recent work has placed significant focus on understanding the role of gene
      lesions involving the spliceosomal machinery in leukemogeneis. SRSF2 is a gene
      encoding critical spliceosomal proteins. SRSF2 mutations appear to play an
      important role in pathogenesis of MMOS, particularly in chronic myelomonocytic
      leukemia. Inhibition of splicing may be a new therapeutic approach. E7107, a
      spliceosome inhibitor, has been shown to differentially inhibit splicing more in
      SRSF2-mutant cells leading to decreased leukemia burden in mice. H3B-8800 is a
      small molecule modulator of spliceosome complex and has been shown to lower
      leukemia burden in SRSF2-P95H mutant mice. This review focuses on the incidence
      of mutant SRSF2 across various MMOS as well as recent clinical development of
      spliceosome inhibitors.

PMID- 30275954
TI  - A case of lung tumorlets secondary to pulmonary hypoplasia with recurrent
      haemoptysis.
AB  - Most patients with lung tumorlets are usually asymptomatic, and most diagnoses
      are incidental findings during microscopic lung examinations at autopsy or after
      excision of a tissue lesion. A 73-year-old woman was admitted to our hospital due
      to recurrent haemoptysis. Chest computed tomography demonstrated right inferior
      lobe collapse with bronchiectasis. Bronchoscopic examination revealed the right
      inferior lobar bronchus to be filled with blood clots. Haemoptysis persisted even
      after two arterial embolization trials and occlusion with endobronchial Watanabe
      spigot. Therefore, right lower lobectomy was performed, and multiple tumorlets on
      lobar hypoplasia were observed on histopathological examination of the excised
      specimen. We believe that the haemoptysis in our patient was possibly caused by
      the lung tumorlets secondary to lobar hypoplasia.

PMID- 30275955
TI  - Habitat suitability does not capture the essence of animal-defined corridors.
AB  - Background: Increases in landscape connectivity can improve a species' ability to
      cope with habitat fragmentation and degradation. Wildlife corridors increase
      landscape connectivity and it is therefore important to identify and maintain
      them. Currently, corridors are mostly identified using methods that rely on
      generic habitat suitability measures. One important and widely held assumption is
      that corridors represent swaths of suitable habitat connecting larger patches of
      suitable habitat in an otherwise unsuitable environment. Using high-resolution
      GPS data of four large carnivore species, we identified corridors based on animal
      movement behavior within each individual's home range and quantified the spatial
      overlap of these corridors. We thus tested whether corridors were in fact spatial
      bottle necks in habitat suitability surrounded by unsuitable habitat, and if they
      could be characterized by their coarse-scale environmental composition. Results:
      We found that most individuals used corridors within their home ranges and that
      several corridors were used simultaneously by individuals of the same species,
      but also by individuals of different species. When we compared the predicted
      habitat suitability of corridors and their immediate surrounding area we found,
      however, no differences. Conclusions: We could not find a direct correspondence
      between corridors chosen and used by wildlife on the one hand, and a priori
      habitat suitability measurements on the other hand. This leads us to speculate
      that identifying corridors relying on typically-used habitat suitability methods
      alone may misplace corridors at the level of space use within an individual's
      home range. We suggest future studies to rely more on movement data to directly
      identify wildlife corridors based on the observed behavior of the animals.

PMID- 30275956
TI  - Premedication to reduce anxiety in patients undergoing coronary angiography and
      percutaneous coronary intervention.
AB  - Aims: In this study, we examined the effects of the routinely administration of
      benzodiazepines on reducing periprocedural anxiety versus no premedication.
      Methods: In this open label study, we enrolled 1683 patients undergoing
      diagnostic coronary angiograms (CAG) or percutaneous coronary interventions
      (PCI). Randomisation was simulated by systematically allocating patients in
      monthly rotational periods to lorazepam 1  mg/sl, oxazepam 10  mg/po, diazepam 5 
      mg/po, midazolam 7.5  mg/po or no premedication. Anxiety was measured at four
      different time points using the one-item Visual Analogue Scale for Anxiety (VAS
      score) ranging from 0 to 10. The primary outcome was the difference in anxiety
      reduction (DeltaVAS, preprocedure to postprocedure), between the different
      premedication strategies versus no premedication. Results: Anxiety reduction was
      larger in patients premedicated with lorazepam (DeltaVAS=-2.0, SE=1.6, P=0.007)
      or diazepam (DeltaVAS=-2.0, SE=1.5, p=0.003) compared with patients without any
      premedication (DeltaVAS=-1.4, SE=1.2). The use of midazolam or oxazepam did not
      lead to a significant reduction in anxiety compared with patients who did not
      receive premedication. Additionally, a high number of patients treated with
      midazolam (N=39, 19.8%) developed side effects. Conclusions: In this study, the
      use of lorazepam or diazepam was associated with a significant, but modest
      anxiety reduction in patients undergoing CAG or PCI. This study does not support
      the standard use of oxazepam or midazolam as premedication to reduce anxiety.

PMID- 30275957
TI  - Guideline-defined futility or patient-reported outcomes to assess treatment
      success after TAVI: what to use? Results from a prospective cohort study with
      long-term follow-up.
AB  - Objective: Transcatheter aortic valve implantation (TAVI) provides a significant
      symptom relief and mortality reduction in most patients; however, a substantial
      group of patients does not experience the same beneficial results according to
      physician-determined outcomes. Methods: Single-centre prospective design; the
      population comprises all consecutive patients undergoing TAVI in 2012-2017. TAVI
      futility was defined as the combined endpoint of either no symptomatic
      improvement or mortality at 1 year. We actively gathered telephone follow-up
      using a predefined questionnaire. Results: Guideline defined TAVI futility was
      present in 212/741 patients. Multivariate regression showed lower albumin and non
      transfemoral approach to be predictive for futility. In addition to these,
      chronic obstructive pulmonary disease, lower estimated glomerular filtration
      rate, atrial fibrillation, low-flow-low-gradient aortic stenosis and lower Body
      Mass Index were predictive for 1-year mortality. Patients who showed symptomatic
      benefit estimated the percentage in which their symptoms were remedied higher
      than patients who did not (80% vs 60%, p<0.001). Guideline-defined TAVI futility
      occurs frequently, contrasting with patient-reported outcome measures (PROMs).
      The vast majority in both groups would again choose for TAVI treatment.
      Conclusion: Lower albumin and non-transfemoral access route were predictors for
      guideline-defined TAVI futility, defined as mortality within 1 year or no
      objective symptomatic improvement in New York Heart Association class. Futility
      according to this definition occurred frequently in this study, contrasting with
      much more positive PROMs. The majority of patients would undergo a TAVI again,
      underlining the patients' experienced value of TAVI and putting the definition of
      TAVI futility further on debate. In the near future, less-strict criteria for
      TAVI futility, that is, using a shorter warranted life expectancy and
      incorporating patients' perceived outcomes, should be used.

PMID- 30275959
TI  - Liver abscess caused by Gram-negative spiral bacilli.

PMID- 30275958
TI  - Extensively drug-resistant (XDR) Pseudomonas aeruginosa identified in Lima, Peru
      co-expressing a VIM-2 metallo-beta-lactamase, OXA-1 beta-lactamase and GES-1
      extended-spectrum beta-lactamase.
AB  - Introduction: Pseudomonas aeruginosa has the ability to acquire plasmids and
      other mobile genetic elements that confer resistance to antibiotics. Bacterial
      genes encoding different beta-lactamases (bla), such as metallo-beta-lactamases
      (MBLs) and extended-spectrum beta-lactamases (ESBL), can confer resistance to
      multiple classes of beta-lactam antibiotics. Case presentation: An 83 year old
      female was admitted in 2012 to the Peruvian Naval Hospital, Centro Medico Naval
      'Cirujano Mayor Santiago Tavara' (CEMENA), in Lima, Peru. A midstream urine
      sample was collected and sent to the local CEMENA laboratory for routine urine
      culture. P. aeruginosa was isolated and initial antibiotic susceptibility testing
      showed it to be sensitive to imipenem. The clinicians started a course of
      meropenem, but the patient did not improve. After 5 days, a second urine culture
      was performed and a P. aeruginosa was isolated again, but this time the strain
      showed resistance to imipenem. The treatment course was changed to fosfomycin and
      the patient improved. Phenotypic and molecular laboratory testing to characterize
      the antibiotic resistance were performed, demonstrating the presence of both MBL
      and ESBL genes. Conclusion: To our knowledge, this is the first report of a P.
      aeruginosa XDR clinical isolate that co-expresses an MBL (VIM-2), OXA-1 beta
      lactamase and the ESBL (GES-1) in Peru. It is also the first report of a VIM
      carbapenemase in Peru.

PMID- 30275960
TI  - Staphylococcus haemolyticus epididymo-orchitis and bacteraemia: a case report.
AB  - Introduction: Although more often recognized as a culprit in female urinary tract
      infection, coagulase-negative staphylococci (CoNS) can cause severe genitourinary
      infections in men. While positive blood cultures with CoNS are usually thought to
      be contaminants, in the setting of a severe genito-urinary infection they can
      represent true infection. Case presentation: We present the case of a 70-year-old
      male without a central venous catheter or urinary catheter who developed
      Staphylococcus haemolyticus bloodstream infection secondary to epididymo
      orchitis. Conclusion: This case highlights the importance of prompt recognition
      of serious CoNS infections, including bacteraemia, in the setting of CoNS
      genitourinary tract infections.

PMID- 30275961
TI  - Mycobacterium xenopi systemic infection in a domestic fiery-shouldered conure
      bird (Pyrrhura egregia).
AB  - Introduction: Mycobacterium xenopi is a rare opportunistic pathogen mainly
      causing infections in immunocompromised human patients or those with underlying
      chronic structural lung disease. Cases of disease in veterinary medicine remain
      scarce. Few animal species, including birds, are suspected of being vectors of
      the disease and there has not yet been a report of clinical disease in birds. We
      report the first case, to our knowledge, of systemic infection in a domestic
      bird. Case presentation: A female fiery-shouldered conure was submitted after
      death for necropsy following episodes of heavy breathing. The necropsy revealed
      multiple granulomatous lesions within the liver, air sacs and kidneys. Ziehl
      Neelsen stains demonstrated the presence of numerous intralesional acid-fast
      bacilli. PCR assays and culture confirmed the presence of M. xenopi. Conclusion:
      Through this case we hope to describe the characteristics of M. xenopi disease in
      birds and the possible close relationship between animal and human infections.

PMID- 30275962
TI  - Isolated appendiceal endometriosis resulting in intussusception.
AB  - An inverted (intussuscepted) appendix is a rare finding, often mistaken for a
      polyp as it presents with vague symptoms. This can result in misdiagnosis and
      inappropriate management. Diagnosis is usually made through surgery. Rarely,
      endometriosis has been found as the cause of the intussusception. A 42-year-old
      woman presented with frequent loose stools over 2 years, an elevated calprotectin
      over 400 MUg/g faeces (normal <110) and a serum C-reactive protein of 40 mg/l
      (normal <5 mg/l). Endoscopy showed an inverted appendix. Histopathology results
      showed inflammation and ulceration. Laparoscopic appendicectomy was performed
      successfully, and endometriosis was found on the inverted appendix. This is the
      first case reported of an inverted appendix containing endometriosis, in which
      the intussusception of the appendix has been diagnosed on endoscopy. This case
      highlights how endometriosis can involve just the appendix, without any
      involvement of reproductive organs. We suggest considering inverted appendix as a
      differential diagnosis when investigating caecal lesions.

PMID- 30275963
TI  - A community-driven reconstruction of the Aspergillus niger metabolic network.
AB  - Background: Aspergillus niger is an important fungus used in industrial
      applications for enzyme and acid production. To enable rational metabolic
      engineering of the species, available information can be collected and integrated
      in a genome-scale model to devise strategies for improving its performance as a
      host organism. Results: In this paper, we update an existing model of A. niger
      metabolism to include the information collected from 876 publications, thereby
      expanding the coverage of the model by 940 reactions, 777 metabolites and 454
      genes. In the presented consensus genome-scale model of A. niger iJB1325 , we
      integrated experimental data from publications and patents, as well as our own
      experiments, into a consistent network. This information has been included in a
      standardized way, allowing for automated testing and continuous improvements in
      the future. This repository of experimental data allowed the definition of 471
      individual test cases, of which the model complies with 373 of them. We further
      re-analyzed existing transcriptomics and quantitative physiology data to gain new
      insights on metabolism. Additionally, the model contains 3482 checks on the model
      structure, thereby representing the best validated genome-scale model on A. niger
      developed until now. Strain-specific model versions for strains ATCC 1015 and CBS
      513.88 have been created containing all data used for model building, thereby
      allowing users to adopt the models and check the updated version against the
      experimental data. The resulting model is compliant with the SBML standard and
      therefore enables users to easily simulate it using their preferred software
      solution. Conclusion: Experimental data on most organisms are scattered across
      hundreds of publications and several repositories.To allow for a systems level
      understanding of metabolism, the data must be integrated in a consistent
      knowledge network. The A. niger iJB1325 model presented here integrates the
      available data into a highly curated genome-scale model to facilitate the
      simulation of flux distributions, as well as the interpretation of other genome
      scale data by providing the metabolic context.

PMID- 30275964
TI  - Appearance alteration of fruits and vegetables to increase their appeal to and
      consumption by school-age children: A pilot study.
AB  - Picky eating with regard to fruit and vegetables is common among children. This
      study investigated the effectiveness of enhancing the visual appeal of fruit and
      vegetables to increase children's liking and consumption of fruit and vegetables.
      A pre-post experimental design was used, and the control and experimental groups
      were repeatedly exposed to the original food and transformed food, respectively,
      over 6 weeks. Significant differences in the consumption of pumpkin, sweet
      potato, spinach, carrot and aubergine were observed between the groups,
      demonstrating that the appearance appeal of fruit and vegetables improves the
      willingness of children to try disliked fruit and vegetables and increases their
      vegetable consumption.

PMID- 30275965
TI  - What causes fibromyalgia? An online survey of patient perspectives.
AB  - Fibromyalgia is a severe chronic pain condition that affects every aspect of
      life. Causes of the condition remain unclear, and quantitative research cannot
      account for patients' personal illness narratives and perceptions. This online
      survey gathered qualitative accounts of the perceived causes of their condition
      from 596 people with fibromyalgia, which were analyzed thematically. Themes were
      "Bodily assault, ill-health, and change"; "Emotional trauma and distress";
      "Stress and vulnerability"; and "Explaining and authenticating fibromyalgia."
      Discussion focuses on the complexity of causation, the importance of
      understanding and having symptoms validated, and the potential for benefiting
      from patient expertise in building better practitioner-client relationships.

PMID- 30275966
TI  - Feasibility and acceptability of technology-based caregiver engagement strategies
      delivered in a summertime childhood obesity prevention intervention: results from
      an internal pilot of the Camp NERF (Nutrition, Education, Recreation, and
      Fitness) study.
AB  - Background: The most efficacious childhood obesity prevention interventions have
      involved caregivers directly or indirectly. Due to the high reliance on
      technology, research examining technological intervention approaches is
      warranted, particularly during the summer when parents may be more difficult to
      engage and the risk for excess weight gain among children is high. Methods: The
      feasibility and acceptability of a multi-component childhood obesity prevention
      intervention incorporating a caregiver component utilizing technology-based
      approaches-texting and social media-was explored. This was an internal pilot of
      the Camp Nutrition Education Recreation and Fitness (NERF) study, a group RCT for
      school-age children coupled to the USDA Summer Food Service Program. Feasibility
      and acceptability of the technology caregiver engagement component were assessed
      via process outcomes (participation rates) and in-depth interviews. Results:
      Participants (n = 37) were 91.9% female, 91.8% Black, 58.7% low-income, and 75.0%
      overweight/obese. Participation rates in texting and social media were 62.2% and
      < 3%, respectively. Themes emerged from the in-depth interviews were texting
      provides connection; desire more involvement with program; fear social media
      privacy intrusion. Conclusions: Results will be used to inform changes to
      technology-based caregiver engagement strategies to be tested in future
      interventions. Trial registration: Clinical Trials, NCT02908230/09-19-2016.
      Registered 20 September 2016.

PMID- 30275967
TI  - New opportunities for nanoparticles in cancer immunotherapy.
AB  - Background: Recently, cancer immunotherapy has become standard for cancer
      treatment. Immunotherapy not only treats primary tumors, but also prevents
      metastasis and recurrence, representing a major advantage over conventional
      cancer treatments. However, existing cancer immunotherapies have limited clinical
      benefits because cancer antigens are often not effectively delivered to immune
      cells. Furthermore, unlike lymphoma, solid tumors evade anti-cancer immunity by
      forming an immune-suppressive tumor microenvironment (TME). One approach for
      overcoming these limitations of cancer immunotherapy involves nanoparticles based
      on biomaterials. Main body: Here, we review in detail recent trends in the use of
      nanoparticles in cancer immunotherapy. First, to illustrate the unmet needs for
      nanoparticles in this field, we describe the mechanisms underlying cancer
      immunotherapy. We then explain the role of nanoparticles in the delivery of
      cancer antigens and adjuvants. Next, we discuss how nanoparticles can be helpful
      within the immune-suppressive TME. Finally, we summarize current and future uses
      of nanoparticles with image-guided interventional techniques in cancer
      immunotherapy. Conclusion: Recently developed approaches for using nanoparticles
      in cancer immunotherapy have enormous potential for improving cancer treatment.
      Cancer immunotherapy based on nanoparticles is anticipated not only to overcome
      the limitations of existing immunotherapy, but also to generate synergistic
      effects via cooperation between nanoparticles and immune cells.

PMID- 30275968
TI  - Clinical development of photodynamic agents and therapeutic applications.
AB  - Background: Photodynamic therapy (PDT) is photo-treatment of malignant or benign
      diseases using photosensitizing agents, light, and oxygen which generates
      cytotoxic reactive oxygens and induces tumour regressions. Several photodynamic
      treatments have been extensively studied and the photosensitizers (PS) are key to
      their biological efficacy, while laser and oxygen allow to appropriate and
      flexible delivery for treatment of diseases. Introduction: In presence of oxygen
      and the specific light triggering, PS is activated from its ground state into an
      excited singlet state, generates reactive oxygen species (ROS) and induces
      apoptosis of cancer tissues. Those PS can be divided by its specific efficiency
      of ROS generation, absorption wavelength and chemical structure. Main body: Up to
      dates, several PS were approved for clinical applications or under clinical
      trials. Photofrin(r) is the first clinically approved photosensitizer for the
      treatment of cancer. The second generation of PS, Porfimer sodium (Photofrin(r)),
      Temoporfin (Foscan(r)), Motexafin lutetium, Palladium bacteriopheophorbide,
      Purlytin(r), Verteporfin (Visudyne(r)), Talaporfin (Laserphyrin(r)) are
      clinically approved or under-clinical trials. Now, third generation of PS, which
      can dramatically improve cancer-targeting efficiency by chemical modification,
      nano-delivery system or antibody conjugation, are extensively studied for
      clinical development. Conclusion: Here, we discuss up-to-date information on FDA
      approved photodynamic agents, the clinical benefits of these agents. However, PDT
      is still dearth for the treatment of diseases in specifically deep tissue cancer.
      Next generation PS will be addressed in the future for PDT. We also provide
      clinical unmet need for the design of new photosensitizers.

PMID- 30275970
TI  - Injectable hydrogels delivering therapeutic agents for disease treatment and
      tissue engineering.
AB  - Background: Injectable hydrogels have been extensively researched for the use as
      scaffolds or as carriers of therapeutic agents such as drugs, cells, proteins,
      and bioactive molecules in the treatment of diseases and cancers and the repair
      and regeneration of tissues. It is because they have the injectability with
      minimal invasiveness and usability for irregularly shaped sites, in addition to
      typical advantages of conventional hydrogels such as biocompatibility,
      permeability to oxygen and nutrient, properties similar to the characteristics of
      the native extracellular matrix, and porous structure allowing therapeutic agents
      to be loaded. Main body: In this article, recent studies of injectable hydrogel
      systems applicable for therapeutic agent delivery, disease/cancer therapy, and
      tissue engineering have reviewed in terms of the various factors physically and
      chemically contributing to sol-gel transition via which gels have been formed.
      The various factors are as follows: several different non-covalent interactions
      resulting in physical crosslinking (the electrostatic interactions (e.g., the
      ionic and hydrogen bonds), hydrophobic interactions, pi-interactions, and van der
      Waals forces), in-situ chemical reactions inducing chemical crosslinking (the
      Diels Alder click reactions, Michael reactions, Schiff base reactions, or enzyme
      or photo-mediated reactions), and external stimuli (temperatures, pHs, lights,
      electric/magnetic fields, ultrasounds, or biomolecular species (e.g., enzyme)).
      Finally, their applications with accompanying therapeutic agents and notable
      properties used were reviewed as well. Conclusion: Injectable hydrogels, of which
      network morphology and properties could be tuned, have shown to control the load
      and release of therapeutic agents, consequently producing significant therapeutic
      efficacy. Accordingly, they are believed to be successful and promising
      biomaterials as scaffolds and carriers of therapeutic agents for disease and
      cancer therapy and tissue engineering.

PMID- 30275971
TI  - Hypoxic condition enhances chondrogenesis in synovium-derived mesenchymal stem
      cells.
AB  - Background: The chondrogenic differentiation of mesenchymal stem cells (MSCs) is
      regulated by many factors, including oxygen tensions, growth factors, and
      cytokines. Evidences have suggested that low oxygen tension seems to be an
      important regulatory factor in the proliferation and chondrogenic differentiation
      in various MSCs. Recent studies report that synovium-derived mesenchymal stem
      cells (SDSCs) are a potential source of stem cells for the repair of articular
      cartilage defects. But, the effect of low oxygen tension on the proliferation and
      chondrogenic differentiation in SDSCs has not characterized. In this study, we
      investigated the effects of hypoxia on proliferation and chondrogenesis in SDSCs.
      Method: SDSCs were isolated from patients with osteoarthritis at total knee
      replacement. To determine the effect of oxygen tension on proliferation and
      colony-forming characteristics of SDSCs, A colony-forming unit (CFU) assay and
      cell counting-based proliferation assay were performed under normoxic (21%
      oxygen) or hypoxic (5% oxygen). For in vitro chondrogenic differentiation, SDSCs
      were concentrated to form pellets and subjected to conditions appropriate for
      chondrogenic differentiation under normoxia and hypoxia, followed by the analysis
      for the expression of genes and proteins of chondrogenesis. qRT-PCR, histological
      assay, and glycosoaminoglycan assays were determined to assess chondrogenesis.
      Results: Low oxygen condition significantly increased proliferation and colony
      forming characteristics of SDSCs compared to that of SDSCs under normoxic
      culture. Similar pellet size and weight were found for chondrogensis period under
      hypoxia and normoxia condition. The mRNA expression of types II collagen,
      aggrecan, and the transcription factor SOX9 was increased under hypoxia
      condition. Histological sections stained with Safranin-O demonstrated that
      hypoxic conditions had increased proteoglycan synthesis. Immunohistochemistry for
      types II collagen demonstrated that hypoxic culture of SDSCs increased type II
      collagen expression. In addition, GAG deposition was significantly higher in
      hypoxia compared with normoxia at 21 days of differentiation. Conclusion: These
      findings show that hypoxia condition has an important role in regulating the
      synthesis ECM matrix by SDSCs as they undergo chondrogenesis. This has important
      implications for cartilage tissue engineering applications of SDSCs.

PMID- 30275969
TI  - Micro-CT - a digital 3D microstructural voyage into scaffolds: a systematic
      review of the reported methods and results.
AB  - Background: Cell behavior is the key to tissue regeneration. Given the fact that
      most of the cells used in tissue engineering are anchorage-dependent, their
      behavior including adhesion, growth, migration, matrix synthesis, and
      differentiation is related to the design of the scaffolds. Thus, characterization
      of the scaffolds is highly required. Micro-computed tomography (micro-CT)
      provides a powerful platform to analyze, visualize, and explore any portion of
      interest in the scaffold in a 3D fashion without cutting or destroying it with
      the benefit of almost no sample preparation need. Main body: This review
      highlights the relationship between the scaffold microstructure and cell
      behavior, and provides the basics of the micro-CT method. In this work, we also
      analyzed the original papers that were published in 2016 through a systematic
      search to address the need for specific improvements in the methods section of
      the papers including the amount of provided information from the obtained
      results. Conclusion: Micro-CT offers a unique microstructural analysis of
      biomaterials, notwithstanding the associated challenges and limitations. Future
      studies that will include micro-CT characterization of scaffolds should report
      the important details of the method, and the derived quantitative and qualitative
      information can be maximized.

PMID- 30275972
TI  - Layer-by-layer assembled polymeric thin films as prospective drug delivery
      carriers: design and applications.
AB  - Background: The main purpose of drug delivery systems is to deliver the drugs at
      the appropriate concentration to the precise target site. Recently, the
      application of a thin film in the field of drug delivery has gained increasing
      interest because of its ability to safely load drugs and to release the drug in a
      controlled manner, which improves drug efficacy. Drug loading by the thin film
      can be done in various ways, depending on type of the drug, the area of exposure,
      and the purpose of drug delivery. Main text: This review summarizes the various
      methods used for preparing thin films with drugs via Layer-by-layer (LbL)
      assembly. Furthermore, additional functionalities of thin films using surface
      modification in drug delivery are briefly discussed. There are three types of
      methods for preparing a drug-carrying multilayered film using LbL assembly. First
      methods include approaches for direct loading of the drug into the pre-fabricated
      multilayer film. Second methods are preparing thin films using drugs as building
      blocks. Thirdly, the drugs are incorporated in the cargo so that the cargo itself
      can be used as the materials of the film. Conclusion: The appropriate designs of
      the drug-loaded film were produced in consideration of the release amounts and
      site of the desired drug. Furthermore, additional surface modification using the
      LbL technique enabled the preparation of effective drug delivery carriers with
      improved targeting effect. Therefore, the multilayer thin films fabricated by the
      LbL technique are a promising candidate for an ideal drug delivery system and the
      development possibilities of this technology are infinite.

PMID- 30275973
TI  - Synthesis and characterization of thiolated hexanoyl glycol chitosan as a
      mucoadhesive thermogelling polymer.
AB  - Background: Mucoadhesive polymers, which may increase the contact time between
      the polymer and the tissue, have been widely investigated for pharmaceutical
      formulations. In this study, we developed a new polysaccharide-based mucoadhesive
      polymer with thermogelling properties. Methods: Hexanoyl glycol chitosan (HGC), a
      new thermogelling polymer, was synthesized by the chemical modification of glycol
      chitosan using hexanoic anhydride. The HGC was further modified to include thiol
      groups to improve the mucoadhesive property of thermogelling HGC. The degree of
      thiolation of the thiolated HGCs (SH-HGCs) was controlled in the range of 5-10%
      by adjusting the feed molar ratio. The structure of the chemically modified
      polymers was characterized by 1H NMR and ATR-FTIR. The sol-gel transition,
      mucoadhesiveness, and biocompatibility of the polymers were determined by a tube
      inverting method, rheological measurements, and in vitro cytotoxicity tests,
      respectively. Results: The aqueous solution (4 wt%) of HGC with approximately 33%
      substitution showed a sol-gel transition temperature of approximately 41  degrees
      C. SH-HGCs demonstrated lower sol-gel transition temperatures (34 +/- 1 and 31 +/
      1  degrees S) compared to that of HGC due to the introduction of thiol groups.
      Rheological studies of aqueous mixture solutions of SH-HGCs and mucin showed that
      SH-HGCs had stronger mucoadhesiveness than HGC due to the interaction between the
      thiol groups of SH-HGCs and mucin. Additionally, we confirmed that the
      thermogelling properties might improve the mucoadhesive force of polymers.
      Several in vitro cytotoxicity tests showed that SH-HGCs showed little toxicity at
      concentrations of 0.1-1.0 wt%, indicating good biocompatibility of the polymers.
      Conclusions: The resultant thiolated hexanoyl glycol chitosans may play a crucial
      role in mucoadhesive applications in biomedical areas.

PMID- 30275975
TI  - Heterogeneity in clinical sequencing tests marketed for autism spectrum
      disorders.

PMID- 30275976
TI  - The antibacterial efficacy of a foam mouthwash and its ability to remove
      biofilms.
AB  - Objectives/Aims: To evaluate the antimicrobial activity of a newly developed foam
      mouthwash containing a modified lactoperoxidase system in vitro. Materials and
      methods: Biofilms of five bacterial species were developed on hydrophobic and
      hydrophilic surfaces whilst salivary-based biofilm was grown on tooth enamel.
      Each surface was exposed to the foam mouthwash or saline in vitro. Optical
      density and scanning electron microscopy (SEM) was used to determine retention of
      the biofilm following 5 or 30 s exposure time. Results: The foam mouthwash was
      active against biofilms formed by S. aureus, K. rhizophila, M. thailandicus, E.
      coli, and C. violaceum and eliminated significant amount of biofilm from each
      surface; immature 4 h biofilm was less resistant than 24 h biofilm. A 30 s rinse
      showed best performance, with removal of up to 66% of biofilm from the
      hydrophilic surface. SEM imaging confirmed oral biofilm removal from the enamel
      surface after a 5 s rinse with the foam mouthwash. Discussion: Foam mouthwash
      demonstrated a significant impact on growing biofilm when compared against saline
      solution. Growing biofilms were more susceptible to the action of the foam
      mouthwash, which justifies after-meal use of the mouthwash when traditional
      dentifrices may not be accessible. Conclusions: Foam mouthwash can be a
      convenient on-the-go format of oral care products that can be used after meals or
      when needed to reduce the risk of biofilm-associated oral conditions.

PMID- 30275974
TI  - Non-insulin determinant pathways maintain glucose homeostasis upon metabolic
      surgery.
AB  - Insulin is critical for glucose homeostasis, and insulin deficiency or resistance
      leads to the development of diabetes. Recent evidence suggests that diabetes can
      be remitted independent of insulin. However, the underlying mechanism remains
      largely elusive. In this study, we utilized metabolic surgery as a tool to
      identify the non-insulin determinant mechanism. Here, we report that the most
      common metabolic surgery, Roux-en-Y gastric bypass (RYGB), reduced insulin
      production but persistently maintained euglycemia in healthy Sprague-Dawley (SD)
      rats and C57 mice. This reduction in insulin production was associated with RYGB
      mediated inhibition of pancreatic preproinsulin and polypyrimidine tract-binding
      protein 1. In addition, RYGB also weakened insulin sensitivity that was evaluated
      by hyperinsulinemic-euglycemic clamp test and downregulated signaling pathways in
      insulin-sensitive tissues. The mechanistic evidence suggests that RYGB
      predominately shifted the metabolic profile from glucose utilization to fatty
      acid oxidation, enhanced the energy expenditure and activated multiple metabolic
      pathways through reducing gut energy uptake. Importantly, the unique effect of
      RYGB was extended to rats with islet disruption and patients with type 2
      diabetes. These results demonstrate that compulsory rearrangement of the
      gastrointestinal tract can initiate non-insulin determinant pathways to maintain
      glucose homeostasis. Based on the principle of RYGB action, the development of a
      noninvasive intervention of the gastrointestinal tract is a promising therapeutic
      route to combat disorders characterized by energy metabolism dysregulation.

PMID- 30275977
TI  - Identification of Burkholderia fungorum in the urine of an individual with spinal
      cord injury and augmentation cystoplasty using 16S sequencing: copathogen or
      innocent bystander?
AB  - Introduction: People with neuropathic bladder (NB) secondary to spinal cord
      injury (SCI) are at risk for multiple genitourinary complications, the most
      frequent of which is urinary tract infection (UTI). Despite the high frequency
      with which UTI occurs, our understanding of the role of urinary microbes in
      health and disease is limited. In this paper, we present the first prospective
      case study integrating symptom reporting, urinalysis, urine cultivation, and 16S
      ribosomal ribonucleic acid (rRNA) sequencing of the urine microbiome. Case
      presentation: A 55-year-old male with NB secondary to SCI contributed 12 urine
      samples over an 8-month period during asymptomatic, symptomatic, and
      postantibiotic periods. All bacteria identified on culture were present on 16S
      rRNA sequencing, however, 16S rRNA sequencing revealed the presence of bacteria
      not isolated on culture. In particular, Burkholderia fungorum was present in
      three samples during both asymptomatic and symptomatic periods. White blood cells
      of >=5-10/high power field and leukocyte esterase >=2 on urinalysis was
      associated with the presence of symptoms. Discussion: In this patient, there was
      a predominance of pathogenic bacteria and a lack of putative probiotic bacteria
      during both symptomatic and asymptomatic states. Urinalysis-defined inflammatory
      markers were present to a greater extent during symptomatic periods compared to
      the asymptomatic state, which may underscore a role for urinalysis or other
      inflammatory markers in differentiating asymptomatic bacteriuria from UTI in
      patients with NB. The finding of potentially pathogenic bacteria identified by
      sequencing but not cultivation, suggests a need for greater understanding of the
      relationships amongst bacterial species in the bacteriuric neuropathic bladder.

PMID- 30275978
TI  - Rapid incremental closed traction reduction of cervical facet fracture
      dislocation: the Stoke Mandeville experience.
AB  - Study design: Retrospective case series study. Objective: To determine the
      success rate and neurological outcomes of rapid incremental closed traction
      reduction (RICTR) of cervical dislocations with spinal cord compression in the
      National Spinal Injuries Centre (NSIC), between June 2006 and December 2011.
      Setting: Tertiary spinal injuries centre, Stoke Mandeville Hospital, UK. Methods:
      A list of cervical trauma patients who were admitted to NSIC between January 2006
      and December 2011 was retrieved from the hospital's electronic records,
      consultant and admission logbooks. Patients, admitted within 7 days of cervical
      facet dislocation and spinal cord injury (SCI), were included. Retrospective data
      collection and analysis was done using a data collection form and an Excel
      spreadsheet. Results: Seventeen patients have met the eligibility criteria of the
      study. One patient was excluded because he only had nerve root symptoms. The
      procedure was successful in 44% of the cases. Eighty-six percent of patients in
      the successful RICTR group improved in their discharge motor index score (MIS),
      whereas 43% improved in their post-reduction MIS. Overall, 81% of the cohort had
      improvements in their discharge MIS. Conclusion: Our RICTR success rate was low
      compared to the reported average success rate in the literature, likely due to
      delays in admission. Neurological outcomes were favourable in the majority of
      patients at discharge. In our opinion, early admission and RICTR attempts could
      have improved the results and therefore we would recommend that RICTR procedures
      are done for suitable patients in the Emergency Departments of Major Trauma
      Centres (MTC).

PMID- 30275979
TI  - Spinal subdural and epidural hematomas after vertebroplasty for compression
      fracture: a case report.
AB  - Introduction: Vertebroplasty (VP) is a well-known and effective therapeutic
      method for relieving the pain and improving the quality of life of patients with
      vertebral compression fractures. Major complications of VP are infrequent,
      occurring in no more than 1% of such procedures, whereas spinal subdural and
      epidural hematomas are extremely rare complications. Case Presentation: We
      present a unique case of a spinal subdural hematoma (sSDH) (from T4 to T12)
      occurring immediately after VP to treat a traumatic vertebral compression
      fracture, followed by a spinal epidural hematoma (SEH) (from T3 to T12) after the
      decompressive laminectomy, occurring in a 64-year-old patient. After removing of
      the big spinal epidural hematoma, the patient's symptoms improved progressively
      and she recovered after 2 months. Discussion: This is a rare case of sSDH and SEH
      occurring continuously after VP. The pathogenesis may be that the puncture
      damaged the abnormal blood vessel of spinal dura mater. A small-probability event
      is not an impossible event. We hope to bring more attention to the rare
      complications of VP by sharing this unusual case.

PMID- 30275980
TI  - Evaluation of a ketogenic diet for improvement of neurological recovery in
      individuals with acute spinal cord injury: a pilot, randomized safety and
      feasibility trial.
AB  - Study design: Longitudinal, randomized study. Objectives: (1) Test the safety and
      feasibility of a ketogenic diet (KD) intervention in the acute stages of spinal
      cord injury (SCI), (2) assess the effects of a KD on neurological recovery, and
      (3) identify potential serum biomarkers associated with KD-induced changes in
      neurological recovery. Setting: Acute care and rehabilitation facility. Methods:
      The KD is a high-fat, low-carbohydrate diet that includes ~70-80% total energy as
      fat. Seven participants with acute complete and incomplete SCI (AIS A-D) were
      randomly assigned to KD (n = 4) or standard diet (SD, n = 3). Neurological
      examinations, resting energy expenditure analysis, and collection of blood for
      evaluation of circulating ketone levels were performed within 72 h of injury and
      before discharge. Untargeted metabolomics analysis was performed on serum samples
      to identify potential serum biomarkers that may explain differential responses
      between groups. Results: Our pilot findings primarily demonstrated that KD is
      safe and feasible to be administered in acute SCI. Furthermore, upper extremity
      motor scores were higher (p < 0.05) in the KD vs. SD group and an anti
      inflammatory lysophospholipid, lysoPC 16:0, was present at higher levels, and an
      inflammatory blood protein, fibrinogen, was present at lower levels in the KD
      serum samples vs. SD serum samples. Conclusion: Taken together, these preliminary
      results suggest that a KD may have anti-inflammatory effects that may promote
      neuroprotection, resulting in improved neurological recovery in SCI. Future
      studies with larger sample size are warranted for demonstrating efficacy of KD
      for improving neurological recovery.

PMID- 30275981
TI  - The role of miR-106p-5p in cervical cancer: from expression to molecular
      mechanism.
AB  - This study aims to investigate the role of miR-106b-5p in cervical cancer by
      performing a comprehensive analysis on its expression and identifying its
      putative molecular targets and pathways based on The Cancer Genome Atlas (TCGA)
      dataset, Gene Expression Omnibus (GEO) dataset, and literature review.
      Significant upregulation of miR-106b-5p in cervical cancer is confirmed by meta
      analysis with the data from TCGA, GEO, and literature. Moreover, the expression
      of miR-106b-5p is significantly correlated with the number of metastatic lymph
      nodes. Our bioinformatics analyses show that miR-106b could promote cervical
      cancer progression by modulating the expression of GSK3B, VEGFA, and PTK2 genes.
      Importantly, these three genes play a crucial role in PI3K-Akt signaling, focal
      adhesion, and cancer. Both the expression of miR-106b-5p and key genes are
      upregulated in cervical cancer. Several explanations could be implemented for
      this upregulation. However, the specific mechanism needs to be investigated
      further.

PMID- 30275983
TI  - Reported use of reporting guidelines among JNCI: Journal of the National Cancer
      Institute authors, editorial outcomes, and reviewer ratings related to adherence
      to guidelines and clarity of presentation.
AB  - Background: Associations were examined between author-reported uses of reporting
      guidelines to prepare JNCI: Journal of the National Cancer Institute (JNCI)
      submissions, editorial decisions, and reviewer ratings for adherence to reporting
      guidelines and clarity of presentation. Methods: At submission, authors were
      asked if they used reporting guidelines to prepare their manuscript and, if so,
      which one(s). Reviewers rated adherence to reporting guidelines and clarity of
      presentation. Data were gathered using a customized Editorial Manager Enterprise
      Analytics Report for submissions with first or final decisions that were
      submitted between November 1, 2015, and April 30, 2017. Manuscript types that
      would benefit from the use of reporting guidelines were included. All reviews
      were included in the analyses. Numerical values were given to each answer (yes,
      1; no, 0) or reviewer rating (not applicable, 0; fair, 1; poor, 2; good, 3; very
      good, 4; and outstanding, 5), and scores were compared using two-sided t tests.
      Results: Of 2209 submissions included in the analysis, 1144 (51.8%) indicated
      that at least one reporting guideline was used. The STROBE guidelines were the
      most common (n = 531, 24.0%). Of the 2068 (93.6%) submissions that were rejected,
      1105 (50.1%) indicated using reporting guidelines and 963 (43.6%) did not (mean
      [SD] scores of rejected vs not rejected, 0.53 [0.50] vs 0.49 [0.50], P = .47). Of
      the 1033 ratings for adherence to reporting guidelines, mean (SD) scores for not
      rejected vs rejected submissions were 3.2 (1.61) vs 2.9 (1.57) (P = .005), and
      mean (SD) scores for reporting guidelines use vs no use were 3.1 (1.48) vs 2.9
      (1.70) (P = .01). Of the 1036 ratings for clarity of presentation, mean (SD)
      scores for not rejected vs rejected submissions were 3.6 (1.00) vs 3.1 (1.08) (P
      < .001), whereas mean (SD) scores for reporting guidelines use vs no use were 3.3
      (1.04) vs 3.3 (1.10) (P = .64). Conclusions: Among these JNCI submissions,
      reporting the use of reporting guidelines was not associated with editorial
      decisions or with reviewer ratings for clarity of presentation. Reviewer ratings
      for adherence to guidelines and clarity of presentation were associated with
      editorial decisions after peer review, and ratings for adherence to guidelines
      were associated with reported use of reporting guidelines.

PMID- 30275985
TI  - Erratum: Author Correction: Selection and evaluation of an efficient method for
      the recovery of viral nucleic acids from complex biologicals.
AB  - [This corrects the article DOI: 10.1038/s41541-018-0067-3.].

PMID- 30275982
TI  - Misoprostol regulates Bnip3 repression and alternative splicing to control
      cellular calcium homeostasis during hypoxic stress.
AB  - The cellular response to hypoxia involves the activation of a conserved pathway
      for gene expression regulated by the transcription factor complex called hypoxia
      inducible factor (HIF). This pathway has been implicated in both the adaptive
      response to hypoxia and in several hypoxic-ischemic-related pathologies.
      Perinatal hypoxic injury, often associated with prematurity, leads to multi-organ
      dysfunction resulting in significant morbidity and mortality. Using a rodent
      model of neonatal hypoxia and several representative cell lines, we observed
      HIF1alpha activation and down-stream induction of the cell death gene Bnip3 in
      brain, large intestine, and heart which was mitigated by administration of the
      prostaglandin E1 analog misoprostol. Mechanistically, we determined that
      misoprostol inhibits full-length Bnip3 (Bnip3-FL) expression through PKA-mediated
      NF-kappaB (P65) nuclear retention, and the induction of pro-survival splice
      variants. We observed that the dominant small pro-survival variant of Bnip3 in
      mouse cells lacks the third exon (Bnip3DeltaExon3), whereas human cells produce a
      pro-survival BNIP3 variant lacking exon 2 (BNIP3DeltaExon2). In addition, these
      small Bnip3 splice variants prevent mitochondrial dysfunction, permeability
      transition, and necrosis triggered by Bnip3-FL by blocking calcium transfer from
      the sarco/endoplasmic reticulum to the mitochondria. Furthermore, misoprostol and
      Bnip3DeltaExon3 promote nuclear calcium accumulation, resulting in HDAC5 nuclear
      export, NFAT activation, and adaptive changes in cell morphology and gene
      expression. Collectively, our data suggests that misoprostol can mitigate the
      potential damaging effects of hypoxia on multiple cell types by activating
      adaptive cell survival pathways through Bnip3 repression and alternative
      splicing.

PMID- 30275986
TI  - Stepwise development of a simulation environment for operating room teams: the
      example of vertebroplasty.
AB  - Background: Despite the growing importance of medical simulation in education,
      there is limited guidance available on how to develop medical simulation
      environments, particularly with regard to technical and non-technical skills as
      well as to multidisciplinary operating room (OR) team training. We introduce a
      cognitive task analysis (CTA) approach consisting of interviews, structured
      observations, and expert consensus to systematically elicit information for
      medical simulator development. Specifically, our objective was to introduce a
      guideline for development and application of a modified CTA to obtain task
      demands of surgical procedures for all three OR professions with comprehensive
      definitions of OR teams' technical and non-technical skills. Methods: To
      demonstrate our methodological approach, we applied it in vertebroplasty, a
      minimally invasive spine procedure. We used a CTA consisting of document reviews,
      in situ OR observations, expert interviews, and an expert consensus panel.
      Interviews included five surgeons, four OR nurses, and four anesthetists. Ten
      procedures were observed. Data collection was carried out in five OR theaters in
      Germany. Results: After compiling data from interviews and observations, we
      identified 6 procedural steps with 21 sub-steps for surgeons, 20 sub-steps for
      nurses, and 22 sub-steps for anesthetists. Additionally, we obtained information
      on 16 predefined categories of intra-operative skills and requirements for all
      three OR professions. Finally, simulation requirements for intra-operative
      demands were derived and specified in the expert panel. Conclusions: Our CTA
      approach is a feasible and effective way to elicit information on intra-operative
      demands and to define requirements of medical team simulation. Our approach
      contributes as a guideline to future endeavors developing simulation training of
      technical and non-technical skills for multidisciplinary OR teams.

PMID- 30275984
TI  - A new era in cytomegalovirus vaccinology: considerations for rational design of
      next-generation vaccines to prevent congenital cytomegalovirus infection.
AB  - Human cytomegalovirus (HCMV), a member of the beta-herpesvirus family, is the
      most common cause of congenital infection worldwide as well as an important cause
      of morbidity in transplant recipients and immunosuppressed individuals. An
      estimated 1 in 150 infants are infected with HCMV at birth, which can result in
      lifelong, debilitating neurologic sequelae including microcephaly, sensorineural
      hearing loss, and cognitive impairment. Natural maternal immunity to HCMV
      decreases the frequency of reinfection and reduces risk of congenital
      transmission but does not completely protect against neonatal disease. Thus, a
      vaccine to reduce the incidence and severity of infant infection is a public
      health priority. A variety of candidate HCMV vaccine approaches have been tried
      previously, including live-attenuated viruses, glycoprotein subunit formulations,
      viral vectors, and single/bivalent DNA plasmids, but all have failed to reach
      target endpoints in clinical trials. Nevertheless, there is a great deal to be
      learned from the successes and failures of the HCMV vaccine field (both
      congenital and transplant-associated), as well as from vaccine development
      efforts for other herpesvirus pathogens including herpes simplex virus 1 and 2,
      varicella zoster virus, and Epstein-Barr virus. Here, we review those successes
      and failures, evaluating recent cutting-edge discoveries that have shaped the
      HCMV vaccine field and identifying topics of critical importance for future
      investigation. These considerations will inform rational design and evaluation of
      next-generation vaccines to prevent HCMV-associated congenital infection and
      disease.

PMID- 30275990
TI  - Amino Acids and Inherited Amino Acid-Related Disorders.

PMID- 30275989
TI  - Transforming Retinal Photographs to Entropy Images in Deep Learning to Improve
      Automated Detection for Diabetic Retinopathy.
AB  - Entropy images, representing the complexity of original fundus photographs, may
      strengthen the contrast between diabetic retinopathy (DR) lesions and unaffected
      areas. The aim of this study is to compare the detection performance for severe
      DR between original fundus photographs and entropy images by deep learning. A
      sample of 21,123 interpretable fundus photographs obtained from a publicly
      available data set was expanded to 33,000 images by rotating and flipping. All
      photographs were transformed into entropy images using block size 9 and downsized
      to a standard resolution of 100 * 100 pixels. The stages of DR are classified
      into 5 grades based on the International Clinical Diabetic Retinopathy Disease
      Severity Scale: Grade 0 (no DR), Grade 1 (mild nonproliferative DR), Grade 2
      (moderate nonproliferative DR), Grade 3 (severe nonproliferative DR), and Grade 4
      (proliferative DR). Of these 33,000 photographs, 30,000 images were randomly
      selected as the training set, and the remaining 3,000 images were used as the
      testing set. Both the original fundus photographs and the entropy images were
      used as the inputs of convolutional neural network (CNN), and the results of
      detecting referable DR (Grades 2-4) as the outputs from the two data sets were
      compared. The detection accuracy, sensitivity, and specificity of using the
      original fundus photographs data set were 81.80%, 68.36%, 89.87%, respectively,
      for the entropy images data set, and the figures significantly increased to
      86.10%, 73.24%, and 93.81%, respectively (all p values <0.001). The entropy image
      quantifies the amount of information in the fundus photograph and efficiently
      accelerates the generating of feature maps in the CNN. The research results draw
      the conclusion that transformed entropy imaging of fundus photographs can
      increase the machinery detection accuracy, sensitivity, and specificity of
      referable DR for the deep learning-based system.

PMID- 30275987
TI  - The intracellular signalosome of PD-L1 in cancer cells.
AB  - Programmed cell death-1 ligand-1 (PD-L1) overexpression in cancer cells
      accelerates tumor progression. PD-L1 possesses two main pro-oncogenic functions.
      First, PD-L1 is a strong immunosuppressive molecule that inactivates tumor
      specific T cells by binding to the inhibitory receptor PD-1. Second, PD-L1
      function relies on the delivery of intrinsic intracellular signals that enhance
      cancer cell survival, regulate stress responses and confer resistance toward pro
      apoptotic stimuli, such as interferons. Here, we review the current knowledge on
      intracellular signal transduction pathways regulated by PD-L1, describe its
      associated signalosome and discuss potential combinations of targeted therapies
      against the signalosome with PD-L1/PD-1 blockade therapies.

PMID- 30275988
TI  - Morphological Characterization of Emerging Cercariae among Lymnaeid Snails from
      Barangay Cawongan, Padre Garcia, Batangas, Philippines.
AB  - Background and Objectives: Lymnaeid snails are the known intermediate hosts of
      the liver fluke Fasciola spp. and therefore play an important role in the
      parasite's life cycle. The study is conducted to determine specificity of snail
      host-parasite interaction and to determine the snail-trematode infection rate by
      cercarial emergence, characterizing the emerging larvae using standardized key.
      Materials and Methods: A total of 750 snails were collected from a rice field in
      Barangay Cawongan, Padre Garcia, Batangas, from November 2016 to March 2017
      (n=150/month). Preliminary snail identification was based on morphological
      features of the shell. Each snail was acclimatized for 24 hours in a 50-ml
      capacity container before being exposed to strong artificial light. The 150
      snails collected per month were grouped into 5 batches (n=30/batch) with each
      batch receiving different number of light exposures. Emerging cercariae were
      described and characterized using photo-referencing and standardized keys. All
      statistical tests were performed at p<0.05 level of significance using SPSS ver.
      20. Results: The total cercarial shedding rate of the snails studied, as a
      measure of the infected snails, was found to be 35.6% and was positively
      associated with the length of the snail shell [OR = 1.809; 95% CI: 1.471-2.225;
      p<0.001], but not with the weight [OR = 0.003; 95% CI: 0.00-0.275; p=0.012] and
      width of the shell [OR = 0.937; 95% CI: 0.672-1.305]. The rates varied from 29.3%
      to 38.0% based on the frequency of 6-hour light exposure. Appearance of encysted
      forms increased with increasing number of light exposures [OR = 10.27, 95% CI:
      3.04-34.76, p<0.001]. Three distinct cercariae were identified, namely,
      echinostome, longifurcate-pharyngeate distome cercariae (Strigea cercariae), and
      the virgulate xiphidiocercaria, with 26.4%, 2.27%, and 0.67% infection monitored
      by cercarial emergence, respectively. Conclusion: Local lymnaeid snails were
      infected with a single type of trematode larvae and coinfection with multiple
      larvae was rare but was encountered.

PMID- 30275992
TI  - Chronic, Recreational Chloroform-Induced Liver Injury.
AB  - Historically used as an anesthetic, chloroform is a halogenated hydrocarbon that
      is associated with central nervous system depression, arrhythmias, and
      hepatotoxicity. It is no longer used clinically, but accidental and intentional
      poisonings still occur. We report a case of chronic chloroform abuse leading to
      severe hepatotoxicity in a 26-year-old male graduate student. The patient
      presented to the emergency department with a three-day history of abdominal pain,
      dehydration, and scleral icterus. He drank several beers the night before the
      onset of symptoms, but denied taking acetaminophen, ibuprofen, or other drugs. An
      extensive work-up revealed an aspartate aminotransferase (AST) of 13,527 U/L and
      alanine aminotransferase (ALT) of 8,745 U/L, but the cause of his liver injury
      could not be determined. It was not until many months later that the patient
      admitted to inhaling chloroform in the weeks leading up to his illness.

PMID- 30275991
TI  - Retrospective Multivariate Analysis of Data from Children with Suspected
      Appendicitis: A New Tool for Diagnosis.
AB  - Background: Decision-making for management may sometimes be difficult in acute
      appendicitis (AA). Various diagnostic scoring systems exist, but their
      sensitivity and specificity rates are far from ideal. In this study, the
      determination of the predictors and the effect of radiological data and
      developing a new scoring system were aimed. Methods: Medical records of patients
      who were hospitalized for AA between February 2012 and October 2016 were
      retrospectively reviewed. All data were compared between patients with and
      without appendicitis. The multivariate analysis was performed to define
      significant variables and to examine the sensitivity and specificity of each
      group of predictors including radiological data. A new scoring system (NSS) was
      formed and was compared with two existing scoring systems: pediatric appendicitis
      score (PAS) and Alvarado scoring system (ASS) by using reclassification method.
      Results: Negative appendectomy rate was 11.3%. Statistical analysis identified 21
      independently significant variables. The heel drop test had the highest odds
      ratio. Sensitivity and specificity rates of clinical predictors were 84.6% and
      94.8%, respectively. Radiological predictors increased the sensitivity rate to
      86.9%. Sensitivity and specificity rates for PAS, ASS, and NSS were 86.8% and
      83.9%, 84.7% and 81.6%, and 96.8% and 95.6%, respectively. The "re-assessed
      negative appendectomy rate" was 6.2% and false positive results were remarkably
      more common in patients with duration of symptoms less than 24 hours. Conclusion:
      Radiological data improves the accuracy of diagnosis. Containing detailed
      clinical and radiological data, NSS performs superiorly to PAS and ASS, regarding
      sensitivity and specificity without any age limitation. The efficiency of NSS may
      be enhanced by determining different predictors for different phases of the
      inflammatory process.

PMID- 30275994
TI  - Talus Bipartitus: A Rare Anatomical Variant Presenting as an Entrapment
      Neuropathy of the Tibial Nerve within the Tarsal Tunnel.
AB  - Tarsal tunnel syndrome is an entrapment neuropathy of the tibial nerve within the
      tarsal tunnel that lies beneath the retinaculum on the medial side of the ankle.
      It is often underdiagnosed. Talus bipartitus is a rare anatomical variant; only a
      few cases have been described in medical literature. We report a case of a 36
      year-old female with tarsal tunnel syndrome secondary to a talus bipartitus
      undergoing surgical treatment with good clinical outcome. To our knowledge, talus
      bipartitus presenting as tarsal tunnel syndrome has no previous reports. Image
      studies and physical examination are crucial to reach precise diagnosis.

PMID- 30275993
TI  - Iatrogenic Teratoma Rupture during TVOR Complicated with Peritonitis, Pleuritis,
      and Septic Shock.
AB  - Objective: To obtain a better understanding of the clinical course and the
      subsequent complications of teratoma rupture. Case: We report a rare case of
      chemical peritonitis and pleuritis caused by teratoma rupture during
      ultrasonographically guided transvaginal oocyte retrieval (TVOR). The patient
      initially presented with nonspecific and digestive symptoms after TVOR, but the
      condition deteriorated rapidly after three weeks with peritonitis and septic
      shock. Thus, exploratory laparoscopy was performed with the findings of a
      ruptured teratoma at left adnexa, severe adhesions, and purulent fluid in her
      peritoneal cavity. Bilateral pleuritis was also noted after the operation, which
      was suspected to be caused by chemical irritation of the spilled contents of the
      teratoma. The patient's condition improved after surgical treatment and was
      discharged 28 days after admission. Conclusion: Our case showed that the timing
      of peritoneal irritation caused by teratoma rupture converting to severe chemical
      peritonitis was approximately 3 weeks. Physicians should avoid cyst puncture
      during TVOR and closely observe or even perform surgical treatment when
      iatrogenic teratoma ruptures are suspected.

PMID- 30275995
TI  - Primary Hyperparathyroidism due to Parathyroid Adenoma Originated from
      Supernumerary Gland.
AB  - Introduction: The variability of the location of the parathyroid glands is
      directly related to the events that occur during embryonic development. The
      impact that an individual submits more than four parathyroid glands is close to
      13%. However the presentation of a parathyroid adenoma in a supernumerary gland
      is an uncommon event. Case report: A 30-year-old man diagnosed with primary
      hyperparathyroidism with matching findings on ultrasonography and scintigraphy
      for parathyroid adenoma localization lower left regarding the thyroid gland. A
      cervicotomy explorer showed four orthotopic parathyroid glands. The biopsy of the
      inferior left gland was normal. No signs of adenoma were seen in the biopsy.
      Following mobilization of the ipsilateral thyroid lobe, fifth parathyroid gland
      was found increased significantly in size than proceeded to remove, confirming
      the diagnosis of adenoma. After the excision, the levels of serum calcium and
      parathyroid hormone were normalized. Conclusions: The presentation of a
      parathyroid adenoma in a supernumerary gland is a challenge for the surgeon. The
      high sensitivity having different imaging techniques has been a key to locate
      preoperatively the pathological parathyroid gland. Analytical or clinical
      persistence of primary hyperparathyroidism after parathyroid surgery can occur if
      the location of the adenoma is a supernumerary or ectopic gland location.

PMID- 30275996
TI  - Ventral Stabilization of a T2-T3 Vertebral Luxation via Median Sternotomy in a
      Dog.
AB  - An 8-year-old neutered male miniature Poodle presented for evaluation of a
      suspected T3-L3 lesion with cervical component following vehicular trauma.
      Magnetic resonance imaging and computed tomography revealed a T2-T3 luxation with
      right displacement of T3. A T2 caudal endplate fracture was present as well as
      multifocal noncompressive bulges of cervical intervertebral discs. Conservative
      management failed and ventral stabilization of C7-T4 was performed via a median
      sternotomy. Paired String-of-Pearls plates were placed on the ventral aspect of
      vertebrae. Eight weeks postoperatively, the dog was ambulatory with moderate
      pelvic limb paraparesis. A luxation of T2-T3 is uncommon in small animals and
      surgical stabilization is poorly described in literature. This case report
      demonstrates the use of a ventral approach to cranial thoracic vertebral
      stabilization with a successful outcome.

PMID- 30275997
TI  - New RP-HPLC Method Development and Validation for Dorzolamide in Ophthalmic
      Dosage Form.
AB  - A reversed phase liquid chromatographic method with UV detection at 254 nm for
      dorzolamide assay in ophthalmic solutions was developed and validated.
      Chromatographic separation was achieved on a Zorbax SB C18 (250 mm * 4.6 mm, 5
      um) column kept at 30 degrees C with an isocratic mixture of mobile phase
      (phosphate buffer, pH 2.5, and acetonitrile, 90 : 10 v/v) at a flow rate of 0.8
      mL/min. The method was validated for its specificity, linearity, accuracy,
      precision, limit of detection, limit of quantification, and robustness based on
      ICH guidelines. The validation studies revealed satisfactory results. The
      proposed method has been applied for the quantification of dorzolamide in
      commercial samples. The developed method is fast, simple, specific, accurate, and
      sensitive, hence can be applied for routine quality control analysis of
      dorzolamide in pharmaceutical dosage form.

PMID- 30275998
TI  - Surgical Treatment of Gastroesophageal Junction Cancer.
AB  - Although the incidence of gastroesophageal junction (GEJ) adenocarcinoma has been
      increasing worldwide, no standardized surgical strategy for its treatment has
      been established. This study aimed to provide an update on the surgical treatment
      of GEJ adenocarcinoma by reviewing previous reports and propose recommended
      surgical approaches. The Siewert classification is widely used for determining
      which surgical procedure is used, because previous studies have shown that the
      pattern of lymph node (LN) metastasis depends on tumor location. In terms of
      surgical approaches for GEJ adenocarcinoma, a consensus was reached based on two
      randomized controlled trials. Siewert types I and III are treated as esophageal
      cancer and gastric cancer, respectively. Although no consensus has been reached
      regarding the treatment of Siewert type II, several retrospective studies
      suggested that the optimal treatment strategy includes paraaortic LN dissection.
      Against this background, a Japanese nationwide prospective trial is being
      conducted to determine the proportion of LN metastasis in GEJ cancers and to
      identify the optimal extent of LN dissection in each type.

PMID- 30275999
TI  - Preoperative Nodal 18F-FDG Avidity Rather than Primary Tumor Avidity Determines
      the Prognosis of Patients with Advanced Gastric Cancer.
AB  - Purpose: This study investigated whether the metabolic avidity of primary tumors
      and/or metastatic lymph nodes (LNs) measured by 18F-fluorodeoxyglucose (18F-FDG)
      positron emission tomography/computed tomography (PET/CT) was related to survival
      after surgery in patients with advanced gastric cancer (AGC). Materials and
      Methods: One hundred sixty-eight patients with AGC who underwent preoperative 18F
      FDG PET/CT and curative resection were included. The 18F-FDG avidity of the
      primary gastric tumor and LNs was determined quantitatively and qualitatively.
      The diagnostic performance of 18F-FDG PET/CT was calculated, and the prognostic
      significance of 18F-FDG avidity for recurrence-free survival (RFS) and overall
      survival (OS) was assessed. Results: In all, 51 (30.4%) patients experienced
      recurrence, and 32 (19.0%) died during follow-up (median follow-up duration, 35
      months; range, 3-81 months); 119 (70.8%) and 33 (19.6%) patients showed 18F-FDG
      avid primary tumors and LNs, respectively. 18F-FDG PET/CT showed high sensitivity
      (73.8%) for the detection of advanced pathologic T (pT >=3) stage and high
      specificity (92.2%) for the detection of advanced pN (>=2) stage. 18F-FDG avidity
      of LNs was significantly associated with RFS (P=0.012), whereas that of primary
      tumors did not show significance (P=0.532). Univariate and multivariate analyses
      revealed that 18F-FDG avidity of LNs was an independent prognostic factor for RFS
      (hazard ratio=2.068; P=0.029). Conclusions: 18F-FDG avidity of LNs is an
      independent prognostic factor for predicting RFS. Preoperative 18F-FDG PET/CT can
      be used to determine the risk and prognosis of patients with AGC after curative
      resection.

PMID- 30276000
TI  - Enhanced Recovery after Surgery for Gastric Cancer Patients Improves Clinical
      Outcomes at a US Cancer Center.
AB  - Purpose: Enhanced recovery after surgery (ERAS) protocols for gastric cancer
      patients have shown improved outcomes in Asia. However, data on gastric cancer
      ERAS (GC-ERAS) programs in the United States are sparse. The purpose of this
      study was to compare perioperative outcomes before and after implementation of an
      GC-ERAS protocol at a National Comprehensive Cancer Center in the United States.
      Materials and Methods: We reviewed medical records of patients surgically treated
      for gastric cancer with curative intent from January 2012 to October 2016 and
      compared the GC-ERAS group (November 1, 2015-October 1, 2016) with the historical
      control (HC) group (January 1, 2012-October 31, 2015). Propensity score matching
      was used to adjust for age, sex, number of comorbidities, body mass index, stage
      of disease, and distal versus total gastrectomy. Results: Of a total of 95
      identified patients, matching analysis resulted in 20 and 40 patients in the GC
      ERAS and HC groups, respectively. Lower rates of nasogastric tube (35% vs. 100%,
      P<0.001) and intraabdominal drain placement (25% vs. 85%, P<0.001), faster
      advancement of diet (P<0.001), and shorter length of hospital stay (5.5 vs. 7.8
      days, P=0.01) were observed in the GC-ERAS group than in the HC group. The GC
      ERAS group showed a trend toward increased use of minimally invasive surgery
      (P=0.06). There were similar complication and 30-day readmission rates between
      the two groups (P=0.57 and P=0.66, respectively). Conclusions: The implementation
      of a GC-ERAS protocol significantly improved perioperative outcomes in a western
      cancer center. This finding warrants further prospective investigation.

PMID- 30276001
TI  - Sarcopenia and Post-Operative Morbidity and Mortality in Patients with Gastric
      Cancer.
AB  - Purpose: Surgical resection for gastric adenocarcinoma is associated with
      significant post-operative morbidity and mortality. The aim of this study was to
      assess the prognostic significance of sarcopenia in patients undergoing resection
      for gastric adenocarcinoma with respect to post-operative morbidity and survival.
      Materials and Methods: A retrospective analysis was conducted on a cohort of
      consecutive patients who underwent surgical resection for gastric adenocarcinoma
      between 2008 and 2014. Patient demographics, radiological parameters, and
      pathological data were collected. OsiriX software (Pixmeo) was used to measure
      skeletal muscle area, which was normalized for height to calculate skeletal
      muscle index. Results: A total of 56 patients (41 male, 15 female; mean age, 68.4
      +/- 11.9 years) met the inclusion criteria. Of these, 36% (20 of 56) of the
      patients were sarcopenic pre-operatively. Both sarcopenic and non-sarcopenic
      patient groups were equally matched with the exception of weight and body mass
      index (P=0.036 and 0.001, respectively). Sarcopenia was associated with a
      decreased overall survival (log-rank P=0.003) and was an adverse prognostic
      predictor of overall survival in multivariate analysis (hazard ratio, 10.915;
      P=0.001). Sarcopenia was a predictor of serious in-hospital complications in
      multivariate analysis (odds ratio, 3.508; P=0.042). Conclusions: In patients
      undergoing curative resection for gastric cancer, there was a statistically
      significant association between sarcopenia and both decreased overall survival
      and serious post-operative complications. The measurement and reporting of
      skeletal muscle index on pre-operative computed tomography should be considered.

PMID- 30276002
TI  - Impact of Various Types of Comorbidities on the Outcomes of Laparoscopic Total
      Gastrectomy in Patients with Gastric Carcinoma.
AB  - Purpose: With increasing life expectancy, the presence of comorbidities has
      become a major concern in elderly patients who require surgery. However, little
      is known about the impact of different comorbidities on the outcomes of
      laparoscopic total gastrectomy (LTG). In this study, we investigated the impact
      of comorbidities on postoperative complications in patients undergoing LTG for
      gastric carcinoma. Materials and Methods: We retrospectively reviewed the cases
      of 303 consecutive patients who underwent LTG for gastric carcinoma between 2005
      and 2016. The associations between each comorbidity and postoperative
      complications were assessed using univariate and multivariate analyses. Results:
      A total of 189 patients (62.4%) had one or more comorbidities. Hypertension was
      the most common comorbidity (37.0%), followed by diabetes mellitus (17.8%),
      chronic viral hepatitis (2.6%), liver cirrhosis (2.6%), and pulmonary (27.1%),
      ischemic heart (3.3%), and cerebrovascular diseases (2.3%). The overall
      postoperative morbidity and mortality rates were 20.1% and 1.0%, respectively.
      Patients with pulmonary disease significantly showed higher complication rates
      than those without comorbidities (32.9% vs. 14.9%, respectively, P=0.003);
      patient with other comorbidities showed no significant difference in the
      incidence of LTG-related complications. During univariate and multivariate
      analyses, pulmonary disease was found to be an independent predictive factor for
      postoperative complications (odds ratio, 2.14; 95% confidence interval, 1.03
      4.64), along with old age and intraoperative bleeding. Conclusions: Among the
      various comorbidities investigated, patients with pulmonary disease had a
      significantly higher risk of postoperative complications after LTG. Proper
      perioperative care for optimizing pulmonary function may be required for patients
      with pulmonary disease.

PMID- 30276003
TI  - Who Can Perform Adjuvant Chemotherapy Treatment for Gastric Cancer? A Multicenter
      Retrospective Overview of the Current Status in Korea.
AB  - Purpose: To investigate the current status of adjuvant chemotherapy (AC) regimens
      in Korea and the difference in efficacy of AC administered by surgical and
      medical oncologists in patients with stage II or III gastric cancers. Materials
      and Methods: We performed a retrospective observational study among 1,049
      patients who underwent curative resection and received AC for stage II and III
      gastric cancers between February 2012 and December 2013 at 29 tertiary referral
      university hospitals in Korea. To minimize the influence of potential confounders
      on selection bias, propensity score matching (PSM) was used based on binary
      logistic regression analysis. The 3-year disease-free survival (DFS) rates were
      compared between patients who received AC administered by medical oncologists or
      surgical oncologists. Results: Between February 2012 and December 2013 in Korea,
      the most commonly prescribed AC by medical oncologists was
      tegafur/gimeracil/oteracil (S-1, 47.72%), followed by capecitabine with
      oxaliplatin (XELOX, 16.33%). After performing PSM, surgical oncologists (82.74%)
      completed AC as planned more often than medical oncologists (75.9%), with
      statistical significance (P=0.036). No difference in the 3-year DFS rates of
      stage II (P=0.567) or stage III (P=0.545) gastric cancer was found between the
      medical and surgical oncologist groups. Conclusions: S-1 monotherapy and XELOX
      are a main stay of AC, regardless of whether the prescribing physician is a
      medical or surgical oncologist. The better compliance with AC by surgical
      oncologists is a valid reason to advocate that surgical oncologists perform the
      treatment of AC for stage II or III gastric cancers.

PMID- 30276004
TI  - The Impact of Preoperative Low Body Mass Index on Postoperative Complications and
      Long-term Survival Outcomes in Gastric Cancer Patients.
AB  - Purpose: The aim of this study was to investigate the impact of preoperative low
      body mass index (BMI) on both the short- and long-term outcomes in patients with
      gastric cancer. Materials and Methods: A total of 510 patients with gastric
      cancer were divided into the following 3 groups: low BMI group (<=18.5 kg/m2,
      n=51), normal BMI group (18.6-24.9 kg/m2, n=308), and high BMI group (>=25.0
      kg/m2, n=151). Results: There were significantly more stage III/IV patients in
      the low BMI group than in the other groups (P=0.001). Severe postoperative
      complications were more frequent (P=0.010) and the survival was worse (P<0.001)
      in the low BMI group. The subgroup analysis indicated that survival was worse in
      the low BMI group of the stage I/II subgroup (P=0.008). The severe postoperative
      complication rate was higher in the low BMI group of the stage III/IV subgroup
      (P=0.001), although the recurrence rate and survival did not differ in the stage
      III/IV subgroup among all the BMI groups. Low BMI was an independent poor
      prognostic factor in the stage I/II subgroup (disease-free survival: hazard ratio
      [HR], 13.521; 95% confidence interval [CI], 1.186-154.197; P=0.036 and overall
      survival: HR, 5.130; 95% CI, 1.644-16.010; P=0.005), whereas low BMI was an
      independent risk factor for severe postoperative complications in the stage
      III/IV subgroup (HR, 17.158; 95% CI, 1.383-212.940; P=0.027). Conclusions:
      Preoperative low BMI in patients with gastric cancer adversely affects survival
      among those with stage I/II disease and increases the severe postoperative
      complication rate among those with stage III/IV disease.

PMID- 30276005
TI  - Safety of Laparoscopic Radical Gastrectomy in Gastric Cancer Patients with End
      Stage Renal Disease.
AB  - Purpose: The surgical outcomes of end-stage renal disease (ESRD) patients
      undergoing radical gastrectomy for gastric cancer were inferior compared with
      those of non-ESRD patients. This study aimed to evaluate the short- and long-term
      surgical outcomes of ESRD patients undergoing laparoscopic gastrectomy (LG) and
      open gastrectomy (OG) for gastric cancer. Materials and Methods: Between 2004 and
      2014, 38 patients (OG: 21 patients, LG: 17 patients) with ESRD underwent
      gastrectomy for gastric cancer. Comparisons were made based on the
      clinicopathological characteristics, surgical outcomes, and long-term survival
      rates. Results: No significant differences were noted in the clinicopathological
      characteristics of either group. LG patients had lower estimated blood loss
      volumes than OG patients (LG vs. OG: 94 vs. 275 mL, P=0.005). The operation time
      and postoperative hospital stay were similar in both the groups. The
      postoperative morbidity for LG and OG patients was 41.1% and 33.3%, respectively
      (P=0.873). No significant difference was observed in the long-term overall
      survival rates between the 2 groups (5-year overall survival, LG vs. OG: 82.4%
      vs. 64.7%, P=0.947). Conclusions: In ESRD patients, LG yielded non-inferior short
      and long-term surgical outcomes compared to OG. Laparoscopic procedures might be
      safely adopted for ESRD patients who can benefit from the advantages of minimally
      invasive surgery.

PMID- 30276006
TI  - Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy as Treatment
      Options for Peritoneal Metastasis of Advanced Gastric Cancer.
AB  - Purpose: This study aimed to examine the outcomes of cytoreductive surgery (CRS)
      and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal
      metastasis (PM) of advanced gastric cancer (AGC). Materials and Methods: Between
      May 2015 and June 2017, 38 CRS and HIPEC procedures were performed in patients
      with PM of AGC at the Dankook University Hospital. We prospectively collected and
      analyzed data regarding PM grade, morbidity and mortality rates, and short-term
      follow-up results (median, 13.5 months). Results: The mean peritoneal cancer
      index was 15 (range, 0-39). Complete cytoreduction was achieved in 21 patients
      (55.2%), whereas complications occurred in 16 (42.1%) and 2 (5.7%) patients died.
      The overall median patient survival time was 19 months. The patients who
      underwent complete cytoreduction had a median survival time of 26 months, which
      was significantly longer than the median survival time of 16 months in the
      patients who did not undergo complete cytoreduction (P=0.006). Conclusions: CRS
      with HIPEC may have a beneficial effect in patients with PM of AGC. However, the
      rates of complications and mortality associated with this combined therapeutic
      approach are high. Therefore, this treatment should be performed only in selected
      patients by surgeons experienced in the field of gastric cancer with PM.

PMID- 30276007
TI  - Long-term Survival after Repeated Local Therapy and Salvage Chemotherapy for
      Recurrent Metastases from Gastric Cancer: a Case Report and Literature Review.
AB  - We report a rare case of long-term survival in a patient who received local
      therapy and salvage chemotherapy for recurrent metastases, along with a
      literature review. A 65-year-old male patient underwent subtotal gastrectomy for
      advanced gastric adenocarcinoma. Six months after gastrectomy, 2 metastatic intra
      abdominal lymph node enlargements were detected, which were treated with
      radiotherapy. At 55 months after gastrectomy, an abdominal wall mass was
      detected, which was treated by surgical resection. The patient received 5
      fluorouracil/leucovorin/irinotecan chemotherapy for 27 months before and after
      radiotherapy and docetaxel chemotherapy for 6 months after surgical resection of
      the abdominal wall metastasis. At the last visit, 7.8 years since the initial
      resection of the primary gastric cancer and 6.2 years since detection of the
      first metastases, the patient was disease-free and required no further
      chemotherapy. This case suggests that repeated local therapy offers potential for
      long-term survival in a carefully selected subset of patients with recurrent
      metastases.

PMID- 30276009
TI  - ERRATUM.

PMID- 30276011
TI  - IS PRE-PERFORMANCE MASSAGE EFFECTIVE TO IMPROVE MAXIMAL MUSCLE STRENGTH AND
      FUNCTIONAL PERFORMANCE? A SYSTEMATIC REVIEW.
AB  - Background: Although pre-performance massage is frequently used in sports
      settings, the evidence regarding its effects on muscle strength and functional
      performance is equivocal.Purpose: The purpose of this systematic review was to
      synthesize the findings of randomized controlled trials (RCTs) investigating the
      effects of pre-performance massage on strength and functional performance.Study
      Design: Systematic review with qualitative analysis. Methods: Eight electronic
      databases were searched from inception until June 2017. Methodological quality of
      included studies were assessed using Physiotherapy Evidence Database scale. Data
      was synthesized qualitatively. Results: Nine crossover RCTs with varied
      methodological qualities met inclusion criteria. Six out of nine studies had low
      quality, while two were of moderate-quality and one was high-quality. Following
      the descriptive analysis using within-group effect sizes of interventions used in
      included studies, no evidence was found to support the use of any kind of massage
      interventions (passive manual massage or self-massage) to enhance maximal
      strength, sprint or jump performances of young healthy subjects. In fact, there
      appears to be limited evidence which implies the negative effects of passive
      manual massage. In particular, longer-duration (> 9 minutes) of massage
      interventions tended to result in negative effects on lower-limb maximal
      strength, sprint performance and jump height. Conclusion: In conclusion, the use
      of longer-duration pre-performance massage cannot be recommended for enhancing
      young athletes' strength and performance in sprint and vertical jump. More high
      quality RCTs are necessary to examine overall effects of pre-performance massage
      on athletes' performance. Level of Evidence: 1a.

PMID- 30276010
TI  - ACCURACY OF THE LEVER SIGN TO DIAGNOSE ANTERIOR CRUCIATE LIGAMENT TEAR: A
      SYSTEMATIC REVIEW WITH META-ANALYSIS.
AB  - Background: The Lever sign has gained recent notoriety for its purported anterior
      cruciate ligament (ACL) diagnostics and simplicity of performance. Purpose: The
      purpose of this systematic review with meta-analysis is to summarize the
      diagnostic accuracy of the Lever sign for use during assessment of the knee for
      an ACL tear in subjects with suspected acute and chronic knee injury. Study
      Design: Systematic review with meta-analysis. Methods: A computer-assisted
      literature search of MEDLINE, CINAHL, and EMBASE databases using keywords related
      to diagnostic accuracy of the knee joint. The Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for the search
      and reporting phases of the study. Quality assessment of bias and applicability
      was conducted using the Quality of Diagnostic Accuracy Studies (QUADAS). Mixed
      effects models were used to summarize accuracy. Results: Eight articles, with
      only two demonstrating high quality, were included. Six of the articles were
      included in a meta-analysis. Diagnostic values, utilizing arthroscopy as a gold
      standard, were: pooled SN 0.55 (95% CI 0.22 to 0.84), pooled SP 0.89 (95% CI 0.44
      to 0.99), positive likelihood ratio (+LR) 9.2 (95% CI 0.70 to 46.1), negative
      likelihood ratio (-LR) 0.58 (95% CI 0.18 to 1.28). Post-test probability with a
      positive finding (57% sampling prevalence) reached 92% (95% CI 83 to 97%). Post
      test probability with a negative finding (57% sampling prevalence) reached 43%
      (95% CI 39 to 47%). Conclusions: Based on limited evidence of heterogeneous
      methodological quality, the Lever sign can moderately change post-test
      probability to rule in an ACL tear. These results should be interpreted
      cautiously due to a limited number of studies, with small sample sizes and study
      quality affecting test accuracy. Future investigation should be expanded to
      include additional high-quality studies examining diverse clinical contexts, as
      they become available, to enable a more comprehensive clinical examination of
      this test. Level of evidence: 3aPROSPERO Registration # CRD42018084954.

PMID- 30276008
TI  - 3-Aryl-2,5-Dihydropyrroles via Catalytic Carbonyl-Olefin Metathesis.
AB  - Herein, we describe the development of a synthetic strategy towards chiral 3
      pyrrolines based on the design principle of iron(III)-catalyzed carbonyl-olefin
      metathesis. This approach takes advantage of commercially available amino acids
      as chiral pool reagents and FeCl3 as a Lewis acid catalyst. Our strategy is
      characterized by its operational simplicity, mild reaction conditions and
      functional group tolerance. Investigations show that an electron-deficient
      nitrogen protecting group overcomes limitations arising from competitive binding
      of the Lewis acid catalyst to unfavorable Lewis basic sites, which ultimately
      enables catalytic turnover.

PMID- 30276012
TI  - TEST-RETEST RELIABILITY OF THE LIMITS OF STABILITY TEST PERFORMED BY YOUNG ADULTS
      USING NEUROCOM(r) VSR SPORT.
AB  - Background: A reliable measure of dynamic postural control is needed for
      inclusion in the sports-related concussion assessment battery. Currently, there
      is not a clinical gold standard. The Limits of Stability (LOS) test has potential
      to be a useful tool to collect objective data on important dynamic postural
      stability variables. Psychometric properties of the LOS test with healthy young
      adults are yet to be established. Hypothesis/Purpose: The purpose of this study
      was to examine the intra-session and test-retest reliability for the LOS on the
      NeuroCom(r) VSR Sport when performed by young adults. Study Design: Reliability
      study. Methods: Twenty-seven healthy university students completed four trials of
      the LOS in each of two testing sessions one week apart. Relative reliability was
      measured within each session with an intraclass correlation coefficient
      (ICC[3,k]) for Session 1 and Session 2, respectively, on each of the five
      dependent variables (movement velocity [MVL], directional control [DCL], maximum
      excursion [MXE], endpoint excursion [EPE], and reaction time [RT]) provided by
      the Neurocom. Test-retest reliability was assessed using a repeated-measures
      analysis of variance along with an ICC (3,k) for relative reliability. An ICC
      value of 0.90 or higher was defined as having a high reliability, moderate
      reliability for ICC values between 0.80-0.89, and below 0.80 as questionable.
      Results: The reliability within each session for LOS composite scores for MVL,
      DCL, and MXE was moderate to high (ICC[3,k]=0.89-0.95). These same three
      variables also had high levels of test-retest reliability (ICC[3,k]=0.95-0.96).
      EPE and RT had moderate reliability over time (ICC[3,k]=0.88) but differences for
      within session reliability. Conclusions: LOS provides a reliable measure of
      dynamic postural control for young adults. Two trials are recommended at baseline
      with the first being an adaptation trial to ensure accuracy of findings. Care
      needs to be taken when interpreting EPE and DCL scores on post-injury tests due
      to a learning effect for those variables. Level of Evidence: 2c.

PMID- 30276013
TI  - EVALUATION OF VERTICAL AND HORIZONTAL SACCADES USING THE DEVELOPMENTAL EYE
      MOVEMENT TEST COMPARED TO THE KING-DEVICK TEST.
AB  - Background: Oculomotor function is impaired when an individual has a concussion
      and as such, it is important to identify tests that are able to assess oculomotor
      impairment. The King-Devick (K-D) test assesses horizontal saccadic eye movement
      and attention. The Developmental Eye Movement (DEM) test is designed to identify
      oculomotor dysfunction in children. It measures both horizontal and vertical
      saccades. The K-D test shows promise as a concussion-screening tool and part of a
      multifactorial assessment. The DEM has not been tested as a concussion assessment
      tool, but the neuroanatomical control of horizontal and vertical saccades
      originates from different areas of the brain, so one might expect to see
      differences in performance on the K-D and DEM tests when administered to
      concussed patients. First, it is important to determine if performance on the DEM
      and K-D tests, particularly with respect to the measurement of vertical and
      horizontal saccades, is similar in a healthy population.Hypothesis/Purpose: The
      primary purpose was to evaluate the relationship between horizontal and vertical
      saccade tests over repeated trials in normal, healthy subjects. A secondary
      purpose of this study was to determine the number of trials needed to reach a
      performance plateau for both the DEM and K-D tests.Study Design: This study used
      a prospective cohort research design. Methods: Forty-two healthy non-concussed
      participants (22 males, 20 females; mean age, 24.2 +/- 2.92 years) completed six
      repeated trials of both the DEM, and then six trials of the K-D test in a single
      testing session. Trials within each test were performed in random order and
      participants were offered short rest breaks as needed between test
      administrations. Results: Results indicated strong correlations, r=.67, or
      greater, between measurements of horizontal and vertical saccades. Performance
      plateaued on the K-D at trial three and on the DEM at trial two for both
      horizontal and vertical saccades. Conclusion: It appears that the DEM and K-D
      tests measure similar constructs in healthy individuals and that no additional
      information is provided by assessment of vertical saccades. Additional studies
      are required to investigate the usefulness of the DEM in concussed individuals.
      Level of Evidence: 3: Laboratory study with repeated measures.

PMID- 30276014
TI  - THE RELATIONSHIP BETWEEN TRUNK ROTATION, UPPER QUARTER DYNAMIC STABILITY, AND THE
      KERLAN-JOBE ORTHOPAEDIC CLINIC OVERHEAD ATHLETE SHOULDER AND ELBOW SCORE IN
      DIVISION I COLLEGIATE PITCHERS.
AB  - Hypothesis/Purpose: The purpose of this study was to assess relationships between
      active trunk rotation range of motion (TROM), upper quarter dynamic stability,
      and composite and individual item KJOC scores in collegiate baseball pitchers. A
      secondary purpose was to determine whether differences exist between baseball
      pitchers with and without an injury history in terms of their performance on
      TROM, upper quarter dynamic stability, and composite and individual KJOC scores.
      It was hypothesized that increased TROM and upper quarter dynamic stability are
      associated with better (higher) KJOC scores and pitchers with an injury history
      would exhibit lower KJOC scores compared to uninjured pitchers. Study Design:
      Cross-sectional Cohort Study. Methods: Thirty-six college pitchers were assessed
      for TROM, performance on the Upper Quarter Y-Balance Test (YBT-UQ) and they also
      completed the KJOC. Subjects were grouped based on previous injury history:
      injured, required surgery, (IS, n=9), injured, no surgery, (INS, n=6), and
      uninjured (UI, n=21). Pearson's Correlations were used to assess relationships
      between clinical measurements and the KJOC. One-way ANOVAs were used to assess
      differences in TROM, YBT-UQ, and KJOC scores between groups (P<0.05). Results: No
      significant relationships were detected between TROM measures and KJOC composite
      scores (throwing arm: r = .239, p = 0.16; non-throwing arm: r=.291, p = 0.09). A
      moderate relationship was found between the YBT-UQ and the KJOC scores (throwing
      arm: r = .413, p = 0.01; non-throwing arm: r=.380, p = 0.02). The mean KJOC
      scores for item 1 (warm-up limitations) were significantly different between all
      three groups (IS: 6.7, INS: 9.7, UI: 9.1; p = 0.015). Mean scores on item 5
      (strain on relationships with coaches) and item 8 (limitations in competition
      endurance) were significantly different between the IS and UI groups (Item 5 =
      IS: 7.8, UI: 9.5, p = 0.02; Item 8=IS: 6.4, UI: 8.8, p = 0.04). Conclusion: A
      positive moderate association was found between upper quarter dynamic stability
      as measured by the YBT-UQ and the KJOC. Pitchers with no surgical history had
      better KJOC scores for warm up time, competitive endurance, and impact on team
      relationships. Level of Evidence: 3.

PMID- 30276015
TI  - THE IMPACT OF WARM-UP ON YOUTH GOLFER CLUBHEAD SPEED AND SELF-REPORTED SHOT
      QUALITY.
AB  - Background/Purpose: Physical preparation in golf is now considered a key
      component of the game. With players becoming more athletic, warm-up has become an
      important area in a player's preparation for practice and competition. Much of
      the research to date has focused on the adult golfer, showing potential for
      improvements in clubhead speed, driving distance and shot quality, as well as
      reductions in injury risk. However, there is currently no work specifically
      investigating the impacts of warm-up in youth golf. The aim of this study was to
      examine the impact of a club only warm-up and a dynamic exercise routine followed
      by a club warm-up on club head speed and self-reported shot quality. Methods:
      Using a counterbalanced repeated measures design, eight male and 13 female youth
      golfers completed a control (no warm-up), club only warm-up and an exercise based
      dynamic warm-up followed by club warm-up on three non-consecutive days. In each
      session, players were required to hit 10 maximal effort shots with a driver and
      clubhead speed (CHS) was recorded using a launch monitor alongside self-reported
      shot quality scores. Results: Statistically significant improvements in clubhead
      speed and self-reported shot quality were seen in the dynamic warm-up combined
      with club warm-up. No significant differences were seen in the club-warm up only
      or control groups for either clubhead speed or self-reported shot quality.
      Conclusion: A combined dynamic physical warm-up and club warm-up improves
      clubhead speed and self-reported shot quality in youth golfers. However, a club
      warm-up alone does not seem to be sufficient in eliciting these same
      improvements. Level of Evidence: 3.

PMID- 30276016
TI  - FOUR WEEKS OF ROLLER MASSAGE TRAINING DID NOT IMPACT RANGE OF MOTION, PAIN
      PRESSURE THRESHOLD, VOLUNTARY CONTRACTILE PROPERTIES OR JUMP PERFORMANCE.
AB  - Background: Roller massagers are popular devices that are used to improve range
      of motion (ROM), enhance recovery from muscle soreness, and reduce pain under
      acute conditions. However, the effects of roller massage training and training
      frequency are unknown. Purpose: The objective was to compare two different roller
      massage training frequencies on muscle performance. Study Design: Randomized
      controlled intervention study. Methods: Twenty-three recreationally active
      university students were randomly allocated to three groups: control (n=8;),
      rolling three (3/W; n=8;) and six (6/W; n=7) times per week for four weeks. The
      roller massage training consisted of unilateral, dominant limb, quadriceps and
      hamstrings rolling (4 sets x 30 seconds). Both legs of participants were tested
      pre- and post-training for active and passive hamstrings and quadriceps range of
      motion (ROM), electromyography (EMG) activity during a lunge movement, unilateral
      countermovement jumps (CMJ), as well as quadriceps and hamstrings maximum
      voluntary isometric contraction (MVIC) forces and electromechanical delay.
      Finally, they were tested for pain pressure threshold at middle and distal
      segments of their quadriceps and hamstrings. Results: There were no significant
      training interactions for any measure with the exception that 3/W group exhibited
      6.2% (p=0.03; Effect Size: 0.31) higher CMJ height from pre- (38.6 +/- 7.1 cm) to
      post-testing (40.9 +/- 8.1 cm) for the non-dominant limb. Conclusions: Whereas
      the literature has demonstrated acute responses to roller massage, the results of
      the present study demonstrate no consistent significant training-induced changes.
      The absence of change may highlight a lack of muscle and myofascial morphological
      or semi-permanent neurophysiological changes with rolling. Levels of Evidence:
      2c.

PMID- 30276018
TI  - VALIDITY AND RELIABILITY OF THE FITBIT FLEXTM AND ACTIGRAPH GT3X+ AT JOGGING AND
      RUNNING SPEEDS.
AB  - Background: Monitoring levels of physical activity, as an outcome or in guiding
      rehabilitation, is challenging for clinicians. Personal activity monitors are
      increasing in popularity and provide potential to enhance rehabilitation
      protocols. However, research to support the validity and reliability of these
      devices at jogging and running speeds is limited. Purpose: The purpose of this
      study was to evaluate the validity of the Fitbit FlexTM and ActiGraph GT3X + for
      measuring step count at jogging and running speeds. A secondary purpose was to
      examine inter-device reliability of the Fitbit FlexTM. Study Design: Cross
      sectional study. Methods: Thirty healthy participants aged between 19 and 50
      years, completed a treadmill protocol at jogging and running speeds (8 km/h to 16
      km/h). Treadmill speed was progressively increased by intervals of 2 km/h. Each
      interval was four minutes in duration with a two minute rest period between
      stages. Participants were encouraged to continue through the graded exercise test
      until they reached the maximum running speed that they felt they could maintain
      for four minutes. Step count data was collected for Fitbit FlexTM devices and the
      ActiGraph GT3X+. Video analysis of step count was used as the criterion measure.
      Results: At speeds of 8 to 14 km/h Mean Absolute Percentage Errors were <=1% for
      the Fitbit FlexTM and the ActiGraph GT3X + when compared to step count via video
      analysis. Standard Error of Measurement between the three Fitbit FlexTM devices
      was <= 7 steps for speeds of 8 to 14 km/h and varied between 9 to 19 steps at 16
      km/h. Fitbit FlexTM devices showed good to excellent between device reliability
      at speeds of 8 to14 km/h (ICC 0.723 to 0.999; p <= 0.001). Greater variability
      was evident with the low participant numbers at 16 km/h (ICC 0.527 to 0.896; p >=
      0.02). Conclusion: Both the Fitbit FlexTM and the ActiGraph GT3X + provide a
      valid account of steps taken at jogging and running speeds up to 14 km/hr,
      attainable by non-elite runners on a treadmill. Fitbit FlexTM devices provide
      equivalent step count output to each other, enabling comparison between devices
      during treadmill jogging and running. Level of evidence: 2b.

PMID- 30276017
TI  - ACUTE EFFECTS OF TWO HIP FLEXOR STRETCHING TECHNIQUES ON KNEE JOINT POSITION
      SENSE AND BALANCE.
AB  - Background: Tightness of hip flexor muscles has been recognized as a risk factor
      for various musculoskeletal injuries in the lower extremities. Purpose: The
      purpose of this study was to examine the acute effects of two hip flexor
      stretching techniques (dynamic and hold-relax proprioceptive neuromuscular
      facilitation, HR-PNF) on hip extension (ROM), knee joint position sense (JPS) and
      balance in healthy college age students who exhibit tightness in hip flexor
      muscles. Study Design: Pretest-posttest randomized experimental groups. Methods:
      Thirty-six healthy college age students (mean = 22.37 years) with tight hip
      flexors participated in this study. Hip extension ROM, knee joint position sense
      and dynamic balance were tested pre- and post-stretching using a digital
      inclinometer, an iPod touch and the Y-Balance test, respectively. Subjects were
      randomly divided into dynamic and HR-PNF stretching groups. Three-way mixed
      analysis of variance was utilized to explore if an interaction existed between
      the groups in tested variables. Results: There was a significant effect of time
      on hip extension ROM in both groups (p < 0.001). There was also a significant
      effect of stretch type on hip extension ROM (p = 0.004) favoring hold-relax over
      dynamic stretching group. There was a non-significant effect of time on mean knee
      joint position replication error in both groups. There was a significant main
      effect of time on the Y-Balance test's mean distance of reach to posteromedial
      and posterolateral directions (p < 0.001). There was also a significant main
      effect of directions of reach on distances achieved (p < 0.001) favoring
      posterolateral over posteromedial, and the latter over anterior direction.
      Conclusions: The results of this study demonstrated the effectiveness of both HR
      PNF and dynamic stretching techniques which resulted in a significant acute
      improvement in hip extension ROM and dynamic balance measures, with HR-PNF being
      more effective than dynamic stretch. However, there were no significant
      improvements in knee joint position replication over time in either stretching
      group. Level of Evidence: 2b.

PMID- 30276019
TI  - COMPARISON OF BILATERAL AND UNILATERAL SQUAT EXERCISES ON BARBELL KINEMATICS AND
      MUSCLE ACTIVATION.
AB  - Purpose/Background: Bilateral squats are commonly used in lower body strength
      training programs, while unilateral squats are mainly used as additional or
      rehabilitative exercises. Little has been reported regarding the kinetics,
      kinematics and muscle activation in unilateral squats in comparison to bilateral
      squats. Therefore, the purpose of this study was to compare muscle activity,
      kinetics, and barbell kinematics between unilateral and bilateral squats with the
      same external load per leg in experienced resistance-trained participants.
      Methods: Fourteen resistance-trained males (age 23 +/- 4years, body mass 80.5 +/-
      8.5kg and height 1.81 +/- 0.06m) participated. Barbell kinematics and surface
      electromyography (EMG) activity of eleven muscles were measured during the
      descending and ascending phase of each repetition of the squat exercises.
      Results: Total lifting time was longer and average and peak velocity were lower
      for the bilateral squat (p<0.001). Furthermore, higher muscle activity was found
      in the three quadriceps muscles, biceps femoris (ascending phase) and the erector
      spinae (ascending phase) in the bilateral squat, while greater activation for the
      semitendinosis (descending phase) (p=0.003) was observed for the unilateral squat
      with foot forwards. In the ascending phase, the prime movers showed increased
      muscle activity with repetition from repetition 1 to 4 (p<=0.034). Conclusions:
      Unilateral squats with the same external load per leg produced greater peak
      vertical ground reaction forces than bilateral squats, as well as higher barbell
      velocity, which is associated with strength development and rate of force
      development, respectively. The authors suggest using unilateral rather than
      bilateral squats for people with low back pain and those enrolled in
      rehabilitation programs after ACL ruptures, as unilateral squats are performed
      with small loads (28 vs. 135 kg) but achieve similar magnitude of muscle activity
      in the hamstring, calf, hip and abdominal muscles and create less load on the
      spine. Level of Evidence: 1b.

PMID- 30276020
TI  - ISOKINETIC MUSCLE PERFORMANCE AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION: A
      CASE-CONTROL STUDY.
AB  - Background: and Purpose: Knee muscle strength deficits have been reported in
      individuals who have undergone anterior cruciate ligament reconstruction (ACLR).
      Isokinetic testing is a valid way to assess muscle strength. Some isokinetic
      variables, including the range of motion in the phases to attain a specific
      velocity, load range (sustained specific velocity), time to achieve deceleration,
      and qualitative analysis of the torque-angle velocity relationship, may
      contribute to understanding recovery of these individuals after surgery. Thus,
      the purpose of this study was to compare the load range (LR), time to attain
      velocity (TTAV), deceleration time (DT) phases, total range of motion (ROM), peak
      torque/body mass (PT/BM), angle of peak torque (AngPT) during LR and torque-angle
      velocity relationships (TAV3D) between post ACLR and matched control
      subjects.Study design: Case-control. Methods: Seven men who underwent ACLR and
      seven matched controls were evaluated from four to six months after surgery.
      Testing was performed on a Biodex System 4 isokinetic dynamometer in concentric
      mode at 60, 120 and 300  degrees /s, for knee flexion and extension. Results:
      Statistically significant differences were seen for extension ROM at 60  degrees
      /s where ROM was greater in the control group. PT/BM for extensors was also
      significantly greater in controls by 20 % compared to ACLR at 60 and 120  degrees
      /s. PT/BM for flexors was significantly greater for controls at 60  degrees /s
      (~15 %). TAV3D showed differences in torque and, specifically, the control group
      sustained knee flexion torque for a greater range of motion when compared to the
      ACLR group. Conclusion: The ACL group presented with lower ROM and PT/BM,
      therefore exhibiting worse muscle performance in comparison to the control
      group.Level of Evidence: 3.

PMID- 30276021
TI  - ACUTE EFFECT OF LOW-INTENSITY ECCENTRIC EXERCISE ON ANGLE OF PEAK TORQUE IN
      SUBJECTS WITH DECREASED HAMSTRING FLEXIBILITY.
AB  - Background: Decreased hamstring flexibility and the angle of peak torque (APT)
      occurring at a shorter muscle length are considered risk factors for hamstring
      strain injury. Subjects with decreased hamstring flexibility have an APT that
      occurs at a shorter muscle length; hence, the susceptibility to hamstring strain
      injury could be associated with the APT occurring at a shorter muscle length. Low
      intensity eccentric exercise (ECC-Ex) may reduce hamstring strain injury risk in
      the subjects with decreased hamstring flexibility by allowing the APT to occur a
      longer muscle length. However, the acute effect of low-intensity ECC-Ex on the
      subjects with decreased hamstring flexibility has not been established.
      Hypothesis/Purpose: The purpose of this study was to investigate the acute effect
      of low-intensity ECC-Ex on the peak torque, APT, and hip flexion angle in the
      subjects with decreased hamstring flexibility. The authors hypothesized that low
      intensity ECC-Ex would shift the APT, allowing it to occur at a longer muscle
      length with a minimum decrease of peak torque and hip flexion angle in the
      subjects with decreased hamstring flexibility. Study design: Case-control study.
      Methods: Twelve male college students were categorized into normal group [n = 6
      (12 legs)] and decreased hamstring flexibility group [n = 6 (12 legs)] based on
      the median value of the baseline hip flexion angle (i.e., 80.8  degrees )
      measured by passive straight leg raise test. Peak torque and APT during maximal
      voluntary eccentric knee flexion (via isokinetic dynamometer) and hip flexion
      angle were evaluated before and after the low-intensity ECC-Ex in both groups.
      Results: Low-intensity ECC-Ex shifted the APT, causing it to occur at a longer
      muscle length in the decreased hamstring flexibility group. Low-intensity ECC-Ex
      increased the hip flexion angle and did not change the peak torque in both
      groups. Conclusion: The results of the present study demonstrated that low
      intensity ECC-Ex shifts the APT to occur at a longer muscle length and increases
      the hip flexion angle without a decrease in peak torque in the subjects with the
      decreased hamstring flexibility. Level of Evidence: 3b.

PMID- 30276022
TI  - TESTING INFRASPINATUS AND DELTOID MUSCLES WITH NEW TECHNIQUE TO DECREASE DELTOID
      ACTIVITY DURING TESTING USING EMG ANALYSIS.
AB  - Background: Muscle strength testing of an injured infraspinatus muscle (IM) is
      confounded by actions of synergistic muscles such as the posterior deltoid (PD).
      Hypothesis/Purpose: The purpose of this study was to describe a condition for
      testing of the IM that results in less EMG activity of the PD musculature. The
      researchers hypothesized that greater inhibition of the PD could be achieved
      through active adduction (AA), creating reciprocal inhibition of the PD. Study
      Design: Prospective cohort descriptive study. Methods: Thirty-four (19 females
      and 15 males) right-handed subjects between the ages of 22- 31 (mean 24.2 years +
      /- 6.2) with no previous history of shoulder surgery or pathology participated.
      Surface electrodes were placed over the muscle bellies of the IM and PD of the
      right shoulder along with a ground electrode over the C7 spinous process. EMG
      activity was recorded during resisted external rotation in four different testing
      conditions (seated active and passive adduction, and side-lying active and
      passive adduction). The order of test positions was randomly assigned, and each
      subject completed all four positions with appropriate rest. During AA conditions,
      subjects were asked to adduct the humerus against a sphygmomanometer (using 80%
      maximum force output) while maximal effort external rotation was manually
      resisted. Results: PD activity was significantly less during AA than with no AA
      (p<0.05) in both test positions. No significant difference occurred between IM
      EMG activity in the various test conditions. Conclusion: The results of this
      study suggest that clinicians can reduce activity of the PD without reducing
      activity of the IM by using AA of the humerus before applying manual resistance
      to test the IM during manual muscle testing. Levels of Evidence: 1b.

PMID- 30276023
TI  - A NOVEL APPROACH TO TREATMENT UTILIZING BREATHING AND A TOTAL MOTION RELEASE(r)
      EXERCISE PROGRAM IN A HIGH SCHOOL CHEERLEADER WITH A DIAGNOSIS OF FROZEN
      SHOULDER: A CASE REPORT.
AB  - Background and Purpose: Frozen shoulder (FS) is a condition of the shoulder that
      is characterized by gradual loss of passive and active range of motion of the
      glenohumeral joint. Current treatment recommendations remain unclear due to the
      elusive etiology of FS and absence of nomenclature in the literature. The purpose
      of this case report is to describe the effects of treatment guided by the
      assessment and treatment of a breathing pattern disorder (BPD) coupled with Total
      Motion Release(r) on a 17-year high school cheerleader with a diagnosis of frozen
      shoulder. Case Description: A 17-year-old female cheerleader reported left
      anterolateral chest pain after running during cheer practice. The subject
      continued to experience additional episodes of chest pain and sought out medical
      care at an emergency department where she was diagnosed with a FS. Clinical
      findings upon examination included soft tissue muscular irritability,
      glenohumeral internal and external rotation active range of motion (AROM) loss,
      and a dysfunctional breathing pattern. Intervention consisted of two types of
      breathing interventions and a Total Motion Release(r) (TMR) exercise program. The
      Numeric Rating Scale (NRS), inclinometer measurements to measure AROM, and
      breathing assessment outcomes were used to identify patient-reported outcomes and
      determine treatment effects. Outcomes: The use of the coupled treatment resulted
      in a resolution of the patient's primary complaint, an increase in AROM, and an
      improvement in breathing assessment outcomes. After the first treatment, internal
      rotation (IR) improved by 27 degrees  exceeding a minimal detectable change (MDC)
      of 8 degrees , and after the second treatment, external rotation (ER) improved by
      21 degrees  exceeding a MDC of 9 degrees . Equally important, there were
      improvements in flexion (11 degrees ) and abduction (45 degrees ) exceeding the
      MDC of 8 degrees  and 4 degrees  respectively over the course of treatment. The
      minimal clinically important difference (MCID) on the NRS was exceeded when the
      patient returned to activity. Discussion: In this case report, breathing
      treatments, coupled with a TMR(r) exercise program, were beneficial treatments
      for this patient and provided a clinically meaningful resolution of her
      condition. Clinicians treating patients who display a similar presentation of
      frozen shoulder can consider this a possible treatment option. Levels of
      Evidence: Level 4; single case report.

PMID- 30276024
TI  - ROLLER MASSAGE: SURVEY OF PHYSICAL THERAPY PROFESSIONALS AND A COMMENTARY ON
      CLINICAL STANDARDS- PART II.
AB  - Background: Roller massage (RM) has become a popular intervention prescribed by
      physical therapy (PT) professionals. While this popularity has stimulated an
      increase in research and product development, the trends in the use of RM among
      PT professionals remain undocumented. It is unknown how professionals are using
      RM and integrating the research into their clinical practice. Purpose: To survey
      and document responses in the knowledge, clinical application methods, and use of
      RM devices among PT professionals in the United States. Design: Cross-sectional
      survey study. Methods: A 20-question online survey related to personal and
      professional demographics, beliefs about RM, preferred RM devices, RM exercise
      prescription, and client education was emailed to PT members of the Orthopedic
      and Sports Physical Therapy Sections. Results: A total of 685 sports and
      orthopedic PT professionals completed the survey. Most professionals surveyed
      believe that RM decreases pain (80%), increases mobility (68%), and increases
      range of motion (ROM) (40%). Fifty-one percent believed moderate density rollers
      have the greatest effect. Eighty percent of professionals use a foam roller in
      their practice and 51% recommend to clients. A high proportion of professionals
      prescribe RM for injury treatment (82%) and for pre and post-exercise
      interventions (55%). Most professionals recommend rolling daily for 30 seconds to
      two minutes (55%), per muscle group (64%), at a self-paced cadence (47%). A high
      proportion of professionals use patient reported outcomes (80%), followed by
      joint ROM (59%), and movement-based testing (42%) to measure effects of RM.
      Eighty-seven percent of professionals use live instruction to educate clients and
      91% believe there is a gap in the research. Conclusion: The results of this
      survey should be considered descriptive and a starting point for future research
      to establish a consensus on optimal RM programming, devices, and application
      parameters for different musculoskeletal conditions. The observed responses
      provide some insight into how PT professionals are using RM in their practice and
      highlight the existing gap between the research and professional practice.
      Further research is needed to explore the responses documented in this study.
      Level of Evidence: 3.

PMID- 30276025
TI  - Meeting Milestones: Results of a Quality-Improvement Curriculum to Achieve Cost
      Conscious Care.
AB  - There is a lack of residency education in cost-conscious care. We implemented a
      costing and quality improvement (QI) curriculum to Obstetrics and Gynaecology
      trainees using "Time-Driven Activity-Based Costing (TDABC)," and assessed its
      educational impact. The curriculum included didactic and practical portions. Pre
      and post-knowledge surveys were obtained from 24 residents on self-perceived
      knowledge of key QI principles. Self-perceived knowledge, before and after the
      curriculum, was scored on a Likert scale from 0 to 5 points (0 is the least
      knowledge and 5 is the most knowledge). The mean scores reported an increase in
      knowledge of clinical guideline development (pre = 1.19 vs. post = 3.07, p =
      0.0052); confidence in participating in QI work (pre = 1.75 vs. post = 3.42
      points, p < 0.0001); and knowledge in communicating QI principles (pre = 1.89,
      post = 3.17, p < 0.0003). Our educational programme uses the TDABC method and the
      residents' clinical experience effectively to teach residents cost-conscious
      care.

PMID- 30276026
TI  - Development of 10 single-copy nuclear DNA markers for Euchresta horsfieldii
      (Fabaceae), a rare medicinal plant.
AB  - Premise of the Study: Euchresta horsfieldii (Fabaceae) is a rare and endangered
      medicinal plant in Indonesia with restricted distribution. Single-copy nuclear
      DNA (scnDNA) markers were developed for this species to facilitate further
      investigation of genetic diversity and population structure. Methods and Results:
      We performed RNA-Seq and de novo assembly of the transcriptome. Ten primer sets
      were developed for E. horsfieldii, all of which also amplified in E. japonica and
      E. tubulosa. Conclusions: These scnDNA markers will be an important resource for
      the study of genetic diversity and population structure of E. horsfieldii and
      other species in the genus Euchresta.

PMID- 30276027
TI  - Identification of sieve elements and companion cell protoplasts by a combination
      of brightfield and fluorescence microscopy.
AB  - Premise of the Study: Phloem-limited diseases are becoming increasingly
      pervasive, threatening the existence of crops worldwide. Studies of phloem
      diseases are complicated by the inaccessibility of the phloem tissue. Phloem
      cells are located deep inside the plant body, are interspersed with other cell
      types, are among the smallest cells in the plant kingdom, and make up a small
      percentage of the total cell population in a plant. These properties make phloem
      cells difficult to investigate. Methods: We used leaf midrib protoplasts and a
      combination of organelle-specific dyes including Neutral Red (acidic
      compartments), MitoTracker Green (mitochondria), Hoechst 3342 (nucleus), and
      chloroplast autofluorescence. We examined the protoplasts under light and
      fluorescence microscopy. Results: When observed using brightfield and
      fluorescence microscopy, sieve element protoplasts were distinguished by the lack
      of vacuole and a nucleus, and by containing various mitochondria. Companion cells
      showed a dense cytoplasm and various small vacuoles. They also revealed their
      characteristic large nucleus and abundant mitochondria. Discussion: We present
      evidence that a combination of organelle-specific dyes and autofluorescence
      allows for the identification of sieve elements and companion cell protoplasts
      from citrus leaf tissue.

PMID- 30276028
TI  - Development of microsatellite markers for the resin-yielding, non-timber forest
      product species Boswellia serrata (Burseraceae).
AB  - Premise of the Study: Boswellia serrata (Burseraceae) is an economically
      important aromatic, gum-resin-yielding, non-timber forest tree species.
      Microsatellite markers were developed for B. serrata for the first time to study
      genetic diversity and population structure. Methods and Results: A magnetic bead
      enrichment method was used to develop 16 microsatellite markers, of which 11 were
      polymorphic. The number of alleles per locus in the 60 individuals studied ranged
      from three to 10, and the levels of observed and expected heterozygosity ranged
      from 0.50 to 0.90 and 0.666 to 0.861, respectively. The primers successfully
      amplified in the congeneric species B. ovalifoliolata. Conclusions: These
      microsatellite markers can be used to study the genetic variation and population
      structure of B. serrata and to provide crucial information on population and
      ecological issues for management and conservation of the species.

PMID- 30276029
TI  - Molecular markers for Nassella trichotoma (Poaceae) to study genetic variation in
      New Zealand.
AB  - Premise of The Study: Simple sequence repeat (SSR) markers were developed for the
      study of genetic diversity of New Zealand Nassella trichotoma (Poaceae) and to
      support future studies in its native range. Methods and Results: Genomic DNA was
      extracted from N. trichotoma leaf material and subjected to Roche 454 sequencing.
      From a total of 745 putative SSRs, 48 with di- to pentanucleotide repeats were
      screened, 32 primer pairs were designed, and 15 polymorphic markers were
      optimized for multiplex PCR on 105 N. trichotoma samples from four New Zealand
      regions. Each locus resulted in two to six alleles per locus, and four of the
      loci cross-amplified in N. tenuissima. The mean observed and expected
      heterozygosity ranged from 0.00 to 0.90 and 0.00 to 0.50 per locus, respectively.
      Conclusions: The novel SSR markers are valuable for the study of genetic
      diversity of N. trichotoma and might also be useful for closely related species.

PMID- 30276030
TI  - Regeneration of highland papaya (Vasconcellea pubescens) from anther culture.
AB  - Premise of the Study: Vasconcellea pubescens is an important Caricaceae species
      cultivated in several countries of South America. The objective of this study was
      to investigate different media compositions and plant growth regulators to induce
      plant regeneration. Methods: Anthers were cultured in Murashige and Skoog medium
      with varying concentrations of naphthalene acetic acid (NAA) and 2,4
      dichlorophenoxyacetic acid (2,4-D) plus a cytokinin (N-(2-chloro-4-pyridyl)-N'
      phenylurea). The effect of the basal medium supplemented with auxins and
      cytokinins on shoot regeneration from the induced calli was also evaluated.
      Addition of maltose to the basal medium was also tested. Results: The combination
      of 0.54 MUM NAA and 22.66 MUM 2,4-D induced the highest rate of calli formation.
      Regeneration via organogenesis was obtained in Murashige and Skoog and Woody
      Plant Medium supplemented with maltose and containing 8.88 MUM 6
      benzylaminopurine, 5.71 MUM indoleacetic acid, and 2.28 MUM zeatin. Discussion:
      The plant regeneration protocol reported here permits the development of haploid
      and double haploid plants that can be useful for propagation purposes, allow a
      better molecular understanding of the species, and facilitate the production of
      new cultivars.

PMID- 30276031
TI  - NaOH low-salt method for chloroplast isolation and highly pure cpDNA preparation
      from Aeluropus littoralis.
AB  - Premise of the Study: High-yield pure chloroplast DNA (cpDNA) is necessary for
      whole genome sequencing. Chloroplast extraction with traditional high-salt
      methods causes damage to nuclei and destroys the integrity of organelles, which
      leads to high genomic contamination from the nucleus and mitochondria. To
      overcome this issue, we modified a traditional high-salt method to obtain a new
      approach called the NaOH low-salt method (NLS). Methods and Results: The NLS
      method is based on the mild alkaline lysis of plant cells, followed by
      homogenization with ultrasonic waves and fractionation under reduced osmotic
      pressure. Results showed that this modified protocol worked efficiently to
      extract the intact chloroplast from Aeluropus littoralis and other grasses to
      obtain high-quality pure cpDNA, which was confirmed by fluorescent microscopy,
      qPCR, and Illumina paired-end sequencing analysis. Conclusions: Compared with
      high-salt methods, the NLS method has proven robust for extraction of intact
      chloroplasts and preparation of high-yield pure cpDNA from grasses.

PMID- 30276032
TI  - Recommendations for the Development and Implementation of a Residents as Teachers
      Curriculum.
AB  - Teaching junior residents, medical students and other hospital staff is an
      essential component of a resident physician's job. While resident physicians
      provide much of the teaching for their junior learners, few residents are
      provided with formal training on how to teach effectively. Although some
      Residents as Teachers (RAT) curricula do exist, there is no consensus on how the
      curriculum should be administered, content it should include, and how to assess
      its effectiveness. We seek to provide guidelines and recommendations applicable
      to any residency program seeking to begin or improve upon a RAT curriculum and
      provide suggestions on how to assess its effectiveness.

PMID- 30276033
TI  - Cerebral Fat Embolism: Neuroprotective Goals in an Unusual Cause of Altered
      Mental Status.
AB  - Cerebral fat embolism syndrome is a rare, but potentially lethal, complication
      that may arise from long bone fractures and/or orthopaedic surgery. Neurological
      symptoms are variable, and clinical diagnosis is difficult. We report the case of
      a 75-year-old woman who developed cerebral fat embolism four days after a right
      hip arthroplasty. Maintenance of intracranial pressure monitoring (ICP) within
      normal limits and cerebral tissue oxygenation monitoring (PbtO2) over 20 mmHg
      prevented secondary brain injury and resulted in a gradual improvement of the
      patient's sensorium. This case demonstrates that the use of ICP and PbtO2
      monitoring defines optimal neuroprotective goals.

PMID- 30276034
TI  - Infusion-rate-dependent Acute Neuropathic Pain with Duopa in a Patient with
      Parkinson's Disease and Pre-existing Neuropathy.
AB  - The association of peripheral neuropathy (PN) with the cumulative use of
      levodopa, presumably by vitamin B12 deficiency, has been well-documented in the
      literature. However, less is known about the L-dopa infusion-rate-dependent
      precipitation of pre-existing peripheral neuropathy. We report an unusual case of
      Parkinson's disease in a patient who presented with acute exacerbations of pre
      existing peripheral neuropathy on exceeding certain rates of continuous Carbidopa
      Levodopa Infusions (CLI). We present a case of a 68-year-old gentleman with a 20
      year history of idiopathic Parkinson's disease with bilateral subthalamic nucleus
      deep brain stimulation who was started on Duopa therapy for worsening
      dyskinesias. Workup before initiating Duopa was significant for idiopathic
      sensorimotor axonal polyneuropathy, although the symptoms were well controlled
      with medications. Subsequently, the patient developed severe neuropathic pain
      within 24 hours of initiating Duopa characterized by burning and stinging in his
      feet. Symptoms resolved within four hours of reducing the continuous infusion
      rates without modifying the bolus doses. The patient was doing well with extra
      bolus doses to manage off periods with no further recurrence of symptoms. With
      the support of this case report, we would like to conclude that the acute
      worsening of neuropathic pain with infusion rate or duration of treatment might
      limit the clinical benefits of Duopa and adds to the expanding spectrum of
      neurotoxic side effects associated with this therapy. Further prospective studies
      are needed to monitor the acute worsening of neuropathic pain in patients with
      pre-existing PN, after initiating CLI and its association with doses of
      levodopa/carbidopa.

PMID- 30276036
TI  - Percutaneous Trigger Thumb Release: Special Considerations.

PMID- 30276035
TI  - Closed Incision Negative Pressure Therapy in Oncological Breast Surgery:
      Comparison with Standard Care Dressings.
AB  - Background: Negative pressure wound therapy was developed for treating wounds
      associated with unfavorable healing factors. The principles of the negative
      pressure wound therapy applied on clean and closed surgical incision originate
      the closed incision negative pressure therapy (ciNPT). We evaluated the use of
      ciNPT in the setting of oncological breast surgery. Methods: From January 1,
      2015, to June 31, 2015, we prospectively selected 37 patients undergoing
      oncological breast surgery with a minimum of 4 risk factors. Seventeen patients
      (25 surgeries) voluntary tested ciNPT (ciNPT sample), whereas the remaining 20
      (22 surgeries) chose conventional postsurgery dressing (Standard Care sample).
      Follow-up controls to evaluate postsurgical complications were performed on days
      7, 14, 30, and 90. At 12 months, the quality of life, scar, and overall aesthetic
      outcomes were evaluated with specific questionnaires filled in by surgeon and
      patient. The Standard Care sample was investigated on risk factors associated
      with poor healing. Results: The ciNPT sample showed a significant prevalence of
      high risk factors, especially extensive undermining and bilateral surgeries, and
      a predominance of women under 65 years; only 1/25 (4%) surgical procedures was
      followed by complications. In the Standard Care sample, 10 of 22 surgeries (45%)
      were followed by complications. The difference in complication rate between the 2
      samples was significant. The BIS (Body Image Scale) scores suggested that most
      patients were satisfied with their body image regardless of the type of dressing.
      All other questionnaire scores clearly vouched for a significant superiority of
      the ciNPT. Previous surgery <= 30 days emerged as the surgery-related high risk
      factor most frequently associated with postsurgery complications. Conclusion: The
      results of our study support the use of ciNPT in oncological breast surgery: it
      showed to be a well-tolerated, adaptable, and reliable dressing capable of
      reducing postsurgical complications and improving scar outcomes in patients
      presenting with high risk factors.

PMID- 30276037
TI  - Femoral Condyle Ischaemia: A Possible Complication After Abdominoplasty.

PMID- 30276038
TI  - Ten-year Follow-up After Treating Extended Burn Scar Contracture with an
      Autologous Cultured Dermal Substitute.
AB  - This is the first case report of long-term follow-up after applying the
      autologous cultured dermal substitute to establish the wound bed before split
      skin graft. The results suggest that application of autologous cultured cultured
      dermal substitute contributes to establish the high-quality wound bed for skin
      graft. Split-thickness skin grafts (STSGs) are the gold standard for the
      treatment of burn scar contracture. Young patients in particular may require
      additional skin grafts as they grow, and donor site for skin grafts may be
      limited. We applied autologous cultured dermal substitutes (CDSs) that are
      expected to establish a high-quality wound bed to allow thin STSGs. This is the
      first report of follow-up after application of autologous CDS combined with thin
      STSG. A male neonate suffered third-degree burns (20% of the total body surface
      area) on the back. After 2 years, scar contracture of the gluteal regions were
      released and autologous CDS were applied. Five days after the treatment, a super
      thin (4-6/1,000 per inch) skin grafting was performed. After 3 years, scar
      contracture of the back was released and autologous CDS was applied for 2 weeks.
      Then a split-thick graft was harvested from the same donor site. Ten years after
      the last operation, the width of the skin graft on his back has extended from 5-8
      cm. The contour of the grafted skin is soft, smooth, and can be pinched. This
      long-term result shows the autologous CDS can be expected to establish the high
      quality wound bed that allows thin STSG.

PMID- 30276039
TI  - The Use of a Novel Local Flap Trainer in Plastic Surgery Education.
AB  - With the limitations of work hour restrictions and legal liability surgical
      resident's operative experience is declining. We sought to find other methods of
      training using tactile surgical simulations for plastic surgery. With the
      collaborative efforts of a local artist, a local flap trainer was designed to
      simulate the natural properties, layers, and interaction between layers of
      tissue. A session was held with Plastic Surgery faculty, residents, and students
      to review and practice local flaps using the trainer. Afterward, the participants
      filled out a survey evaluating the simulated skin and tissue model and the
      effectiveness of the class as a teaching model. The survey given had multiple
      questions asking the participant to provide a ranking from 1 to 10. The results
      show that the class utilizing the new suture pad was an effective teaching tool
      with an average score of 9.56. The suture pad was given a score of 6.77 for
      simulating realistic skin. Overall, the group rated increased understanding and
      confidence of local flaps after the class. Surgical skill simulations are
      becoming increasingly more important with the decline of resident operative
      experience. There are limited options for surgical simulations that provide a
      realistic experience. We designed a suture pad that is effective at simulating
      human tissue. The surveys show that using this suture pad in flap workshops
      provides a valuable teaching tool.

PMID- 30276041
TI  - Femoral Osteonecrosis after Medial Femoral Condyle Bone Graft Harvest.
AB  - The medial femoral condyle vascularized graft has become a useful resource in
      reconstructive microsurgery due to the rate of bony union, and the low rate of
      complication. We report osteonecrosis of the medial femoral condyle in a 65-year
      old woman after harvesting a corticocancellous medial femoral condyle graft to
      treat a tarsometatarsal nonunion. We were not able to define whether a vascular
      or mechanical disorder could be the ultimate cause. However, because of the
      severity of the complication, we suggest informing patients who will undergo a
      medial femoral condyle flap about this infrequent complication.

PMID- 30276040
TI  - McKissock's Reduction Mammaplasty Revisited: A Case Series Study with 12-months
      Follow-up.
AB  - Background: Reduction mammaplasty is 1 of the highly challenging yet demanded
      plastic surgeries worldwide. Different techniques have been described, and their
      modifications are always evolving to achieve better aesthetic results. The
      objective of the current study was to explore the efficiency and safety of
      bipedicled McKissock's technique with 3 newly added modifications as a reliable
      procedure for reduction mammaplasty. Methods: The study was conducted in Royal
      Hospital, Cairo, Egypt, during the period from January 2015 to October 2016. It
      included 25 female patients undergoing reduction mammaplasty. All patients were
      evaluated by detailed history, careful physical examination, and photographed pre
      and postoperatively. The new modifications included surgical undermining and
      thinning of the bipedicle for volume reduction and contour enhancement. The
      second modification was a dermal suspension of the lower pole for parenchymal
      support and longer breast shape stability. The third change was an S-shaped
      folding of the upper pole of the pedicle during nipple-areolar complex (NAC)
      transposition. After the operation, all subjects were followed up for 12 months
      to assess the outcomes of the procedure. Results: Twenty-five female patients
      were included in the analysis of this study. The age of the patients ranged from
      22 to 49 years with a mean age of 36.2 (7.3) years. The mean body mass index was
      30.5 +/- 4.3 kg/m2 with a minimum of 24 and a maximum of 38. The average time of
      operation was 4 hours. The resected tissue was 630-980 g. The optimal aesthetic
      appearance of the breasts was achieved at 6-9 months postoperatively and
      marinated to 12 months. The maintenance of improvement was measured by the
      distance between the mid-clavicular point and 12 O'clock point of the NAC
      (12'NAC). It varied between 28 and 43 cm preoperatively (mean +/- SD, 34.12 +/-
      4.19 cm), and between 19 and 22 cm postoperatively (mean +/- SD, 20.70 +/- 1.03
      cm; P < 0.001). The average percentage reduction in mid-clavicular point-NAC
      distance was 38.7% +/- 6.2% with a minimum reduction of 27.6% and a maximum
      48.8%. Moreover, the nipple to inframammary crease distance varied between 16 and
      20 cm preoperatively (mean +/- SD, 16.08 +/- 1.66 cm), and between 8 and 10 cm
      postoperatively (mean +/- SD, 8.04 +/- 0.79 cm; P < 0.001). The patients were
      very satisfied in most of the cases (20 cases), satisfied in 3 cases, and 2 cases
      were unsatisfied as they wanted slightly smaller breasts. No complications
      detected in 18 cases (72%), superficial wound dehiscence at the T-junction in 3
      (12%), and seroma in 1 (4%). Two cases (8%) demanded smaller breasts and 1 case
      (4%) needed a surgical revision of widened scars after 11 months. The major
      drawbacks were NAC sensitivity alteration and the inability to lactate.
      Conclusion: We can conclude that our modifications for the McKissock's technique
      with its maintained aesthetic shape in those patients are a reliable option that
      can be considered, as it is a simple, efficient, and satisfactory method that can
      improve the results of reduction mammaplasty operations.

PMID- 30276042
TI  - Small Finger to Ring Finger Ray Transposition: Modern Surgical Technique and Case
      based Review of the Literature.
AB  - Ray transposition for central digital amputation has been performed following
      traumatic injury to the hand for decades. Small finger to ring finger ray
      transposition has been well described in the literature, with good functional and
      aesthetic outcomes reported. Originally described by Bunnell, the fourth
      metacarpal can be disarticulated and the fifth metacarpal base transposed with
      reconstruction of the intermetacarpal ligament allowing progressive closure
      between the third and fifth rays. However, osteotomy-based transpositions are
      utilized placing the osteotomy at the level of the metacarpal, followed by
      transposition and fixation of the small finger to the base of the ring finger
      metacarpal; or, by making an intracarpal wedge-osteotomy of the hamate with
      subsequent radial translocation of the entire small finger ray. Recent literature
      has suggested the intracarpal wedge osteotomy to be superior technically, and
      with less postoperative complications. However, for this somewhat uncommon
      reconstructive procedure, no high-level evidence exists to determine which of
      these techniques is truly more favorable. Here, we present an interesting case of
      ray amputation and transposition following an isolated fourth metacarpal
      traumatic firearm injury, and comprehensive modern surgical technique. Upon
      review of the literature, small to ring finger ray transposition has been shown
      to have acceptable functional and aesthetic outcomes regardless of the osteotomy
      technique used, and should be considered when the nature of presenting injury and
      the patient's lifestyle and postoperative expectations are appropriate.

PMID- 30276044
TI  - Reconstruction of the Lacrimal Excretory System in the Medial Canthal Region.
AB  - The resection of malignant tumors in medial canthal region may lead to full
      thickness defects including medial canthal ligament and lacrimal duct. There had
      been reports on various reconstructive methods, but none of those methods
      succeeded in lacrimal reconstruction with functional lacrimal excretory system.
      We experienced a case of conjunctival malignant melanoma at the lacrimal caruncle
      and performed new method of the reconstruction for full-thickness defects of the
      medial canthal region with the maintenance of the lacrimal drainage function.

PMID- 30276043
TI  - Evaluation of Safe and Effectiveness of an Injectable Solution Acid Deoxycholic
      Based for Reduction of Localized Adiposities.
AB  - Background: The use of deoxycholic acid to reduce localized fat deposits is a
      procedure that has been in use for about 30 years. Its effectiveness as treatment
      is due to emulsification of phospholipids and therefore, solubilization of the
      biological membranes with resulting fat necrosis. The purpose of the study was to
      assess the effectiveness and the safety of an injectable solution containing
      sodium deoxycholtate 1.25% (DB125), used as intralipotherapy. Methods: The
      effectiveness and safety of DB125 solution have been assessed with a multicentre
      observational prospective study carried out between February and October 2017.
      The 221 selected patients presented with various forms and degrees of localized
      fat in several areas. Intralipotherapy treatments were performed 6 weeks apart
      and until the clinical result was obtained. Aesthetic outcomes were evaluated by
      the authors using preoperative and postoperative photographic documentation and
      by the patients with their level of satisfaction by filling out an anonymous
      form. Major adverse events were reported by each doctor who performed the
      treatment. Results: Two hundred twenty-one patients treated in 273 cases of
      different localized fat deposits. One hundred eighty-five patients who could be
      assessed for final results gave the effectiveness of the treatment an average
      score of 7.4. The failure percentage of the treatment was 3.8%. The medical
      evaluation showed treatment success in 93.5% of cases. Adverse events can be
      divided into 2 groups: minor adverse events, which are very frequent and major
      ones, which are extremely rare. For both groups, the adverse events can be
      ascribed to localized problems in the treatment area. Conclusion: Studies have
      shown that the second-generation solution containing sodium deoxycholate 1.25% is
      effective and safe to treat different localized fat deposits. The high degree of
      effectiveness shown in the study was not associated with a lesser degree of
      handling because, at the doses indicated and with the use of intralipotherapy,
      the occurrence of adverse events was minimal.

PMID- 30276045
TI  - The Utility of a Master of Business Administration Degree in Plastic Surgery:
      Determining Motivations and Outcomes of a Formal Business Education Among Plastic
      Surgeons.
AB  - Background: With the increasing complexity of health care, the knowledge of
      business in medicine is growing more valuable. Plastic surgeons in all practice
      settings are constantly forced to navigate endeavors that could be better faced
      with the leadership, management, and administrative skills honed through a formal
      business education. The purpose of this study was to gather data and draw
      conclusions related to the motivations and outcomes of plastic surgeons with a
      Master of Business Administration degree (MBA). Methods: An online survey was
      distributed to plastic surgeons in the United States who have earned an MBA. The
      survey was divided into 4 main sections: demographics, MBA program description,
      objective assessment, and subjective assessment. Results: The majority of plastic
      surgeons with an MBA are in practice at an academic medical center. The 2 most
      popular tracks of completing the degree are during medical school and after 5
      years of practice. A large proportion of plastic surgeons with an MBA experienced
      changes in their existing career position, namely in patient care and business
      roles outside of clinical practice. The most important skills surgeons
      subjectively felt they had improved as a result of their business education were
      in the areas of leadership, management, and administration. Conclusions: Overall,
      all the plastic surgeons felt that their MBA experience met their expectations
      and would recommend the degree to fellow physicians. Prime motivations included
      adding a new dynamic to their existing career, satisfying entrepreneurial drive,
      and gaining credibility in business, with monetary gains being low on the list.

PMID- 30276046
TI  - The Evolution from Subcutaneous to Prepectoral Prosthetic Breast Reconstruction.
AB  - Prosthetic breast reconstruction is the most common method of reconstruction
      offered to women following mastectomy. Prepectoral breast reconstruction has
      recently reemerged as an alternative technique to the partial and total muscle
      coverage methods. Though this technique has been demonstrated to be safe and
      effective in the recent published literature, many surgeons have been hesitant to
      adopt it out of fear of incurring the same complications associated with
      subcutaneous reconstructions of the past. However, recent advancements in plastic
      surgery including the use of acellular dermal matrices, autologous fat grafting,
      and improved breast implants and improved mastectomy techniques have enabled
      plastic surgeons to revisit the prepectoral space. In this review, the authors
      describe the evolution of prosthetic-based breast reconstruction from
      subcutaneous to prepectoral and review outcomes.

PMID- 30276047
TI  - The Safety, Cosmetic Outcome, and Patient Satisfaction after Inferior Pedicle
      Reduction Mammaplasty for Significant Macromastia.
AB  - Background: Significant macromastia is socially and physically debilitating.
      Reduction mammaplasty in these cases carries significant morbidity. Methods:
      Cases of inferior pedicle reduction mammaplasty performed at the breast unit,
      King Fahd Hospital, Jeddah, Saudi Arabia, over the last 10 years were reviewed.
      Inclusion criteria were cases with significant macromastia in which the distance
      from the supra-sternal notch to the nipple was >= 40 cm. Results: There were 26
      cases of inferior pedicle reduction mammaplasty done for significant macromastia.
      The average age was 34.56 years (range, 16-56 years). The average sternal notch
      to the nipple distance was 43.08 cm (range, 40-49 cm). The average amount of
      breast tissue removed from the right breast was 1,057.6 g (range, 495-2,450) and
      from the left breast was 959.4 g (range, 445-2,100). Postoperatively, 4/26
      (15.4%) had ecchymosis, 9/26 (34.6%) developed T-junction sloughing, 2/26 (7.7%)
      had wound infection, and 1/26 (3.8%) had unilateral partial nipple-areola complex
      ischemia. In 7/26 (26.9%), scars were evident and revision was performed in 4/26
      (15.4%) cases. Variable degrees of upper breast flattening and bottoming were
      seen in most cases; however, these variations were more profound in fatty breasts
      and longer pedicles. The average follow-up period was 26.04 months (range, 3-68
      months). All patients were satisfied with the reduced breast heaviness, but only
      19/26 (73.1%) were highly satisfied with the breast shape and scars. Conclusions:
      In cases of significant macromastia, inferior pedicle reduction mammaplasty is a
      safe procedure. Evident scars, upper breast flattening, and bottoming adversely
      affect the level of satisfaction.

PMID- 30276048
TI  - Isotopic Split-skin Graft for Resurfacing of Deliberate Self-harm Scars.
AB  - We present a novel surgical approach for the revision of deliberate self-harm
      scars. The isotopic skin graft technique employs the harvest of a thin split-skin
      graft from the affected area, excision and closure of wide dermal scars with
      replacement of the graft back onto the harvest site. We present the sequential
      steps of the surgical technique and a case series of 2 patients treated with our
      novel approach.

PMID- 30276050
TI  - Maxillary Reconstruction Using a Gullwing Fibula Osteofascial Flap and Flexor
      Hallucis Longus Muscle.
AB  - The appropriate reconstruction of an infrastructure maxillectomy defect requires
      vascularized bone for maxillary arch restoration, soft tissue bulk for filling
      the residual defect extending up to the orbital floor, and a thin tissue layer
      for resurfacing the palate and adjacent cheek mucosa. Although several free
      tissue flaps have been previously described as reconstructive options, each
      possesses limitations. We describe the fibula osteofascial flap with flexor
      hallucis longus muscle, no skin paddle, and a "gullwing" fascial component, as an
      ideal reconstructive option for these specific maxillary defects. It satisfies
      the necessary requirements of bone, restoration of intraoral surfaces, as well as
      additional soft tissue volume to provide the optimal aesthetic and functional
      result. It also has the added benefit of minimizing morbidity to, and improving
      aesthetics of, the donor site. This is demonstrated through a case presentation
      and review of the existing literature.

PMID- 30276049
TI  - Fat Grafting Can Induce Browning of White Adipose Tissue.
AB  - Background: Fat grafting is commonly used when treating soft-tissue defects.
      However, much of the basic biology behind fat transfer is still uncovered.
      Adipocytes can be divided into energy storing white and energy burning brown
      adipose cells. It is now well known, that also adult humans have metabolically
      active brown adipose tissue (BAT) within white adipose tissue (WAT). Previously
      our group showed that transfer of metabolically inactive WAT into a new
      environment increased the metabolic activity of the fat grafts to resemble the
      activity in the recipient site and that different WAT depots have variation in
      the metabolic activity. This led us to speculate, whether the metabolic increase
      of the graft is a result of "browning" of the transferred WAT toward beige
      adipose tissue. Methods: We investigated the metabolic and histological
      characteristics and BAT marker Ucp1 gene expression in different types of WAT
      grafts placed either in subcutaneous or muscle tissue in mice. Metabolic activity
      of the grafts was investigated by FDG-PET/CT at 4- and 12-week time-points.
      Results: The glucose uptake of all transferred fat types was increased when
      compared with respective control WAT regardless of transfer location. Ucp1 gene
      and protein expression was increased in 4 of 15 intramuscularly placed fat graft
      samples and showed histological resemblance to BAT with multilocular cells.
      Conclusions: Grafting of metabolically inactive fat intramuscularly may induce
      browning of fat grafts toward more active beige adipose tissue. This opens up new
      research areas in exploiting fat grafting in metabolic diseases.

PMID- 30276051
TI  - Institutional Collaboration in Plastic Surgery Research: A Solution to Resource
      Limitations.
AB  - Background: The current climate of health care reform and research funding
      restrictions presents new challenges for academic plastic surgery. Collaboration
      with private enterprise has been associated with greater research productivity in
      the general biomedical literature. This study seeks to analyze publication trends
      in Plastic and Reconstructive Surgery (PRS) to evaluate any changes in
      institutional collaboration over time. Methods: Bibliographic data were
      retrospectively analyzed for all original research and discussion articles
      published in PRS from 2012 to 2016. The institutional affiliation for each
      publication was characterized from its author list as solely academic, private,
      government, or combinations of these (defined here as "institutional
      collaborations"). Annual National Institutes of Health (NIH) funding data were
      also collected over the same period, and associations were analyzed by linear
      regression. Results: In total, 2,595 publications were retrieved from PRS between
      2012 and 2016, of which 2,027 (78.1%) originated solely from academic
      institutions and 411 (15.8%) from institutional collaborations. Although the
      proportion of academic-only publications decreased from 82% to 74%, the
      proportion of institutional collaborations increased from 10% to 20% (P = 0.038).
      Concurrently, NIH funding declined from $33.4 billion to a low of $30.7 billion,
      which was associated with the decreasing proportion of academic-only publications
      (P = 0.025) and increasing proportion of institutional collaborations (P =
      0.0053). Conclusions: Traditional sources of academic research funding have been
      restricted during the politically and financially tumultuous recent years. With
      no signs of improving access to financial resources from the NIH, academic
      plastic surgeons may consider diversifying their institutional partnerships to
      continue pioneering advances in the field.

PMID- 30276053
TI  - A Prospective Study Investigating Fistula Rate Following Primary Palatoplasty
      Using Acellular Dermal Matrix.
AB  - Background: Acellular dermal matrix (ADM) has been described as an adjunct in
      primary cleft palate repair to reduce the fistula rate in several retrospective
      studies (level III or lower); however, current data are insufficient to
      definitively conclude its efficacy for this purpose. The goal of the present
      study was to provide prospective, higher level of evidence data investigating the
      effect of ADM on fistula rate following primary palatoplasty. Methods: A
      prospective clinical trial was conducted in which ADM was used uniformly in all
      primary cleft palate repairs that met inclusion criteria. For comparison, a
      matched control group was identified (retrospectively) from the same
      center/surgeon's database. Primary outcome was the rate of palatal fistula
      formation. Secondary outcomes included bleeding, infection, and delayed healing.
      Results: A total of 130 patients were included in the analysis consisting of 65
      in both the study and control groups. There were no statistically significant
      differences in patient demographics or cleft /surgical characteristics. The
      results demonstrated a fistula rate of 1.5% in the study group versus 12.3% in
      the control group (P = 0.03). The other complications (infection, bleeding,
      delayed healing) were similar between the groups. Conclusion: The study provides
      the highest level of evidence currently available (level II, prospective data)
      investigating the effect of ADM on fistula rate following primary palatoplasty.
      The results demonstrate a low overall fistula rate (1.5%) and suggest there may
      be a clinically significant reduction in fistula formation associated with the
      routine use of ADM in all primary palate repairs.

PMID- 30276052
TI  - Ex Vivo Major Histocompatibility Complex I Knockdown Prolongs Rejection-free
      Allograft Survival.
AB  - Background: Widespread application of vascularized composite allotransplantation
      (VCA) is currently limited by the required lifelong systemic immunosuppression
      and its associated morbidity and mortality. This study evaluated the efficacy of
      ex vivo (after procurement but before transplantation) engineering of allografts
      using small interfering RNA to knockdown major histocompatibility complex I (MHC
      I) and prolong rejection-free survival. Methods: Endothelial cells (ECs) were
      transfected with small interfering RNA targeted against MHC-I (siMHC-I) for all
      in vitro experiments. MHC-I surface expression and knockdown duration were
      evaluated using quantitative polymerase chain reaction (qPCR) and flow cytometry.
      After stimulating Lewis recipient cytotoxic lymphocytes (CTL) with allogeneic
      controls or siMHC-I-silenced ECs, lymphocyte proliferation, CTL-mediated and
      natural killer-mediated EC lysis were measured. Using an established VCA rat
      model, allografts were perfused ex vivo with siMHC-I before transplantation.
      Allografts were analyzed for MHC-I expression and clinical/histologic evidence of
      rejection. Results: Treatment with siMHC-I resulted in 80% knockdown of mRNA and
      87% reduction in cell surface expression for up to 7 days in vitro (P < 0.05).
      Treatment of ECs with siMHC-I reduced lymphocyte proliferation and CTL-mediated
      cytotoxicity (77% and 50%, respectively, P < 0.01), without increasing natural
      killer-mediated cytotoxicity (P = 0.66). In a rat VCA model, ex vivo perfusion
      with siMHC-I reduced expression in all tissue compartments by at least 50% (P <
      0.05). Knockdown prolonged rejection-free survival by 60% compared with nonsense
      treated controls (P < 0.05). Conclusions: Ex vivo siMHC-I engineering can
      effectively modify allografts and significantly prolong rejection-free allograft
      survival. This novel approach may help reduce future systemic immunosuppression
      requirements in VCA recipients.

PMID- 30276054
TI  - Efficacy of Cultured Epithelial Autograft after Curettage for Giant Melanocytic
      Nevus of the Head.
AB  - Cultured epithelial autograft (CEA) is an epithelial sheet prepared from a
      patient's own skin using cell culture. In Japan, CEA (JACE; Japan Tissue
      Engineering Co., Ltd., Gamagori, Japan) was approved and covered by public health
      care insurance for use in the treatment of giant congenital melanocytic nevus
      (GCMN) in 2016. There are several treatment options for GCMN; however, the
      complete removal of a GCMN is usually difficult due to the lack of skin. In this
      report, we describe a case of GCMN in the occipital region that was treated using
      CEA after curettage. A 2-month-old boy had a GCMN of 13 * 21 cm in his occipital
      region. We used full-thickness skin taken from the back of the right auricle to
      prepare CEA under general anesthesia at 4 months of age. Three weeks after
      preparing CEA, we performed curettage of the right half of the GCMN, and CEA was
      grafted onto the wound afterward. CEA took completely, and epithelization was
      observed at 10 days after surgery. We then performed curettage with subsequent
      grafting of CEA on the left half of the GCMN at 7 months of age. CEA took
      completely, and epithelization was observed in this procedure as well with no
      hair loss at 8 months of age. Whether or not curettage can reduce the risk of
      malignant transformation into malignant melanoma of GCMN is unclear; however, the
      application of CEA after curettage may be a promising option for obtaining early
      epithelization.

PMID- 30276055
TI  - Robotic Nipple-sparing Mastectomy and Immediate Breast Reconstruction with Gel
      Implant.
AB  - Background: The experience of application of robotic surgery platform in the
      management of breast cancer was limited. The preliminary experience and results
      of robotic nipple-sparing mastectomy (R-NSM) and immediate breast reconstruction
      (IBR) with Gel implant was reported. Methods: The medical records of patients who
      underwent R-NSM and IBR with Gel implant for breast cancer during the period
      March 2017 to October 2017 were collected from single institution. Data on
      clinicopathologic characteristics, type of surgery, method of breast
      reconstruction, complications, and recurrence were analyzed to determine the
      effectiveness and oncologic safety of R-NSM. Patients' oriented cosmetic outcome
      report was also obtained. Results: A total of 15 patients was analyzed, and the
      mean age of them was 46.5 +/- 10.0 years. The pathologic stage was 30.8% ductal
      carcinoma in situ, 30.8% stage I, 30.8% stage II, and 7.7% stage III. The mean
      operation time was 282.8 +/- 70.4 minutes, and mean hospital stay was 6.7 +/- 1.2
      days. The positive surgical margin rate was 0%. One patient suffered from delayed
      axillary wound healing. Two patients (13.3%) with transit nipple ischemia change,
      but no total nipple areolar complex necrosis case was observed. No local
      recurrence, distant metastasis, or case mortality was found during mean 6.3 +/-
      2.1 months follow-up. All 15 patients were satisfied with the postoperative
      aesthetic outcome. Conclusion: From our preliminary experience, R-NSM and IBR
      with Gel implant is a safe procedure, with good cosmetic results, and could be a
      promising new technique for breast cancer patients indicated for mastectomy.

PMID- 30276056
TI  - Treatment Delay Impact on Open Reduction Internal Fixation of Mandibular
      Fractures: A Systematic Review.
AB  - Background: The impact of mandible fracture treatment delay has been contested in
      the literature for decades, with conventional wisdom favoring earlier surgical
      treatment to prevent postoperative complications, primarily infection. Through a
      systematic review of all available evidence, this study aims to determine whether
      delay to open reduction and internal fixation of traumatic mandibular fractures
      influences outcomes. Methods: MEDLINE, EMBASE, CINAHL, and Web of Science were
      systematically searched for English language literature pertaining to the above
      research question and screened in duplicate. Methodological quality scoring was
      performed using MINORS criteria. Qualitative and quantitative findings from
      relevant studies are presented. Results: Twenty eligible studies including 2,671
      patients had open reduction internal fixation, with or without adjunct
      mandibulomaxillary fixation. All studies were observational cohort or case
      control studies of low methodological quality with a mean MINORS score of 6.5 of
      16 (40.6%) for noncomparative studies and 11.2 of 24 (46.7%) for comparative
      studies. Only 5 of 20 (25%) studies recommended earlier treatment. Due to
      insufficient reporting of data and study heterogeneity, the impact of treatment
      delay on complications could not be quantitatively analyzed. Conclusions: There
      is substantial heterogeneity and no consensus on the definition of "early" versus
      "delayed" surgical treatment for patients with traumatic mandibular fractures.
      The majority of included studies do not make a recommendation for earlier
      treatment. Future, well-designed prospective studies are essential to determine
      if there is an optimal surgical treatment delay of mandibular fractures that
      mitigates the risk of infectious and noninfectious complications.

PMID- 30276057
TI  - Accuracy of Predicted Resection Weights in Breast Reduction Surgery.
AB  - Background: Many insurance carriers continue to deny coverage for reduction
      mammaplasty unless a minimum amount of resected breast tissue per breast is
      achieved during surgery. This study investigates the accuracy of preoperative
      prediction that a minimum weight of 500 g can be resected and evaluates potential
      risk factors for not meeting this insurance requirement. Methods: A retrospective
      review was performed on 445 patients with bilateral symptomatic macromastia who
      sought consultation for breast reduction surgery from 2007 to 2012. Women were
      included for analysis if they had documented predicted resection weights and
      underwent small-to-moderate breast reduction (< 1,000 g per side; n = 323).
      Relevant demographic information, mean predicted resection weight, and the mean
      actual resection weight were collected for analysis. Results: Surgeon prediction
      of resection weight being over 500 g had a positive predictive value of 73%. In
      61 patients (19%), the predicted weights were >= 500 g, but the actual weights
      were < 500 g. Thirty percentage of these 61 patients did not meet either Schnur
      or minimum weight requirements. Women with a body mass index < 30 were at
      significantly increased odds (odds ratio, 3.76; 95% confidence interval, 1.89
      7.48; P = 0.002) of not meeting the minimum weight requirement at surgery
      compared with patients with a body mass index >= 30. Conclusions: The common
      insurance criterion of removing >= 500 g per breast during breast reduction
      surgery are not met in a distinct cohort of women who are clinically appropriate
      candidates. This risk is particularly increased in nonobese women possibly due to
      proportionately smaller breast mass compared with obese women.

PMID- 30276058
TI  - Prevalence and Distribution of Potential Vascularized Composite Allotransplant
      Donors, Implications for Optimizing the Donor-recipient Match.
AB  - Background: Vascularized composite allotransplantation (VCA) is an emerging and
      growing field. Little is known about the prevalence and distribution of the adult
      potential donor population in the United States now that it falls under the
      oversight of the United Network for Organ Sharing (UNOS). Methods: We assessed
      the UNOS database from 2008 to 2015 to estimate the prevalence and distribution
      of adult potential vascularized composite allograft donors. Donor inclusion and
      exclusion criteria were developed in a way to minimize risk to recipients and
      were applied to the dataset. Donors were categorized by factors that influence
      vascularized composite allograft matching including ABO blood type,
      cytomegalovirus status, and ethnicity (correlate for skin color) and sorted by
      UNOS region. Results: Just under half of all brain dead donors met the
      inclusion/exclusion criteria. Blood type O, cytomegalovirus+, White donors
      represented the most frequent donor profile while blood type AB, cytomegalovirus
      , Asian donors were the least common. UNOS region 3 had the most and region 1 had
      the least potential VCA donors per year. Nearly all potential VCA donors were
      solid organ donors with the liver being the most commonly donated solid organ in
      this population. Conclusions: A large portion of the solid organ donor pool would
      qualify as adult vascularized composite allograft donors in the current UNOS
      system. These data will assist transplant teams in determining the prevalence and
      distribution of vascularized composite allograft donors for their individual
      patients awaiting composite allografts based on relevant matching characteristics
      in addition to standard transplant criteria.

PMID- 30276059
TI  - Effect of Keller Funnel on the Rate of Capsular Contracture in Periareolar Breast
      Augmentation.
AB  - Background: Capsular contracture is 1 of the most common complications after
      breast implant surgery and is a major indication for reoperation. Capsular
      contracture is believed to be a multifactorial process that is affected by
      implant texture, incision type, and ultimately pocket contamination. This
      contamination causes a biofilm that leads to capsular contracture. The
      intraoperative use of a Keller funnel is a mechanical way to decrease the
      implant's contact with the skin and ducts, reducing bacterial contamination that
      can cause these biofilms. For this reason, periareolar breast augmentation has
      been less popular among surgeons. The purpose of this study was to examine if
      there was a significant difference between the rates of capsular contracture in
      patients having periareolar breast augmentations with the use of a Keller funnel
      for insertion and those having periareolar breast augmentations without Funnel
      use. Methods: This level 3 retrospective study followed 2 groups of patients, the
      first having periareolar breast augmentations without the use of a funnel for
      insertion (group A; patients n = 15; implants n = 30) and the second having
      periareolar breast augmentations with the use of a funnel for insertion (group B;
      patients n = 151; implants n = 300). Results: The rate of capsular contracture in
      group A was found to be 10% compared with a rate of capsular contracture of 1.3%
      for patients in group B, an 87% reduction (P = 0.0019). Conclusions: According to
      the results found in this study, the rate of capsular contracture in patients
      having periareolar breast augmentations after insertion with a Keller funnel was
      statistically significantly lower than the rate in patients having implants
      inserted without the assistance of a funnel, making the device useful in reducing
      the occurrence of postoperative capsular contracture.

PMID- 30276060
TI  - Peroneal Nerve Repair of a 9 Year Old: Return of Motor Function after 2 Years.
AB  - Major factors that influence functional nerve recovery, postrepair, are length of
      the nerve defect, type of injury, operative technique, time until treatment, and
      age of the patient. We present a severe motor nerve defect in a complicated
      peroneal nerve injury in a 9-year-old that showed functional return after a
      delayed period of 23 months with sural nerve cable grafting. This case revealed
      the increased resiliency and regenerative capacity of motor end plates in young
      patients. In conclusion, autograft for a deep peroneal nerve repair, by means of
      sural nerve graft, proved to be an acceptable option in children.

PMID- 30276061
TI  - Miniature Negative Pressure Dressings on Forearm Donor Sites after Radial Forearm
      Flap Harvest.
AB  - Management of radial forearm donor sites following free flap reconstruction of
      head and neck tumor defects typically requires split-thickness skin grafting.
      Tendon exposure and delayed healing are occasional problems associated with skin
      grafting over the distal forearm musculature. Others have reported the use of
      negative pressure wound therapy (NPWT) devices to bolster split-thickness grafts
      and improve graft take. Although this approach works well, these devices are not
      always approved by third-party payers for outpatient use, requiring patients to
      remain in the hospital or have these devices removed before discharge. The
      authors report outcomes using a miniaturized NPWT device to bolster the skin
      graft on radial forearm free flap donor sites in 10 consecutive patients compared
      with 10 consecutive control patients managed with traditional bolster dressings.
      The 2 groups of patients were similar in terms of demographics, indication for
      reconstruction, and size of donor site. There was less skin graft loss and a
      lower rate of tendon exposure and infection in the miniaturized NPWT device
      group, though these results did not reach statistical significance. Recently
      developed miniaturized, single-use NPWT devices can be reliably used as bolsters
      for skin grafts with some notable advantages over reusable NPWT devices.

PMID- 30276062
TI  - Composite Grafts for Pediatric Fingertip Amputations: A Retrospective Case Series
      of 100 Patients.
AB  - Background: Fingertip amputations are common. This study reports on the outcomes
      of composite grafts used for fingertip amputations in children, measuring graft
      take, predictors of graft take, complications, and patient-reported outcomes.
      Methods: A retrospective case series of consecutive patients (<= 16 years)
      undergoing composite grafts for fingertip amputations in a tertiary pediatric
      hospital, January 06 to December 16, was performed. Information was collected on
      amputations, graft take, and complications. Logistic regression was used to
      analyze factors predicting graft take (partial/complete or failure) including
      age; amputation level; mechanism and time delay to surgery. Patients were
      contacted via post or telephone to ask about functional and cosmetic outcomes and
      their perception of graft take. Results: One hundred patients [57 (57%) males;
      mean age, 4.41 +/- 3.98 years], presenting with 100 fingertip amputations, met
      the inclusion criteria. Amputation mechanism was crush in 75 (75%), avulsion in
      13 (13%), and laceration in 12 (13%). Thirteen (13%) composite grafts survived
      completely, 46 (46%) partially, and 41 (41%) failed. Graft survival was higher in
      children under 4 years (P = 0.016). Seventeen (17%) grafts became infected, 9
      (9%) required a reoperation, 9 (9%) had wound healing complications, and 4 (4%)
      patients developed psychological complications. Patient-reported survival was 33%
      higher than medical-reported survival. Cosmetic issues were the commonest
      complication reported by patients. Patients rated fingertips looking 3.5/5
      normal, and that they were 4/5 satisfied with the appearance. Most patients were
      using their fingers normally by 2-6 months. Conclusions: Composite grafts for
      fingertip amputations mostly only partially survive, but morbidity is low,
      patient satisfaction is high, and acceptable cosmetic and functional outcomes are
      achieved.

PMID- 30276063
TI  - Photometric Evaluation of Long-term Changes in Breast Shape after Breast
      Augmentation and Vertical Mammaplasty.
AB  - Background: Little information is presently available regarding the long-term
      effects of breast augmentation and mammaplasties on breast shape. Existing
      studies typically use 1-dimensional measurements and mean follow-up times seldom
      exceed 1 year. Methods: Twenty women were studied: breast augmentation (n = 5),
      mastopexy (n = 5), augmentation/mastopexy (n = 5), and breast reduction (n = 5).
      For mammaplasties, a vertical method using a medial pedicle and intraoperative
      nipple siting was used in all cases. A 2-dimensional measurement system was used,
      with computer-assisted matching of lateral photographs of the right and left
      breasts. Measurements were evaluated at 3 times: before surgery, 1 year after
      surgery, and 10 years after surgery. Results: Breast implants significantly
      increased breast projection and upper pole projection. The nipple level was
      unchanged. The lower pole level dropped. These changes were preserved at 10
      years. Vertical mastopexy provided a modest increment in breast projection and
      upper pole projection. The nipple level and lower pole level were raised
      significantly. Augmentation/mastopexy boosted breast projection and upper pole
      projection, and also elevated the nipple and lower pole level. Breast reduction
      changes were similar to mastopexy, but with greater elevation of nipple level and
      lower pole level, which were usually lower to start with. Implants increased
      upper pole convexity. Nipple overelevation was avoided by intraoperative nipple
      siting just below the breast apex. Conclusions: These measurements provide new
      information regarding the long-term effects of breast augmentation and vertical
      mammaplasties. This information may be used by plastic surgeons in procedure
      selection and patient counseling.

PMID- 30276064
TI  - Efficacy and Safety of Intravenous Meloxicam in Subjects with Moderate-to-severe
      Pain Following Abdominoplasty.
AB  - Background: A nanocrystal intravenous (IV) formulation of meloxicam is being
      studied with the aim of providing postoperative analgesia. Methods: This
      randomized, multicenter, double-blind, placebo-controlled trial evaluated
      meloxicam IV 30 mg or placebo (<= 3 doses) in 219 subjects undergoing
      abdominoplasty. The primary endpoint was the summed pain intensity difference
      over 24 hours postdose (SPID24). Results: Meloxicam IV-treated subjects had a
      statistically significant reduction in the least squares mean of SPID24 compared
      with placebo-treated subjects (-4,262.1 versus -3,535.7; P = 0.0145). Meloxicam
      IV was associated with statistically significant differences over placebo on
      several other secondary endpoints, including other SPID intervals (ie, SPID12,
      SPID48, and SPID24-48), achievement of perceptible pain relief, the proportion of
      subjects with a >= 30% improvement in the first 24 hours, and Patient Global
      Assessment of pain at hour 48. Meloxicam IV was also associated with a reduction
      in the number of subjects receiving opioid rescue medication during hours 24-48
      and the total number of doses of opioid rescue analgesia. Meloxicam IV was
      generally well tolerated, with the numbers and frequencies of adverse events
      similar to that of the placebo group. There was no evidence of an increased risk
      of adverse events commonly associated with nonsteroidal anti-inflammatory drugs
      including bleeding, thrombotic, cardiovascular, renal, hepatic, cardiovascular,
      injection site, and wound healing events. Conclusion: Meloxicam IV provided
      sustained pain relief and generally was well tolerated in subjects with moderate
      to-severe pain following abdominoplasty.

PMID- 30276065
TI  - Glans Ischemia after Circumcision in a 16-Year-Old Boy: Full Recovery after
      Angiography with Local Spasmolysis, Systemic Vasodilatation, and Anticoagulation.
AB  - Circumcision is one of the most frequent procedures performed by pediatric
      surgeons. A dorsal penile nerve block (DPNB) is commonly used for perioperative
      analgesia. We report the case of a 16-year-old boy with ischemia of the glans who
      presented on the first postoperative day after circumcision under DPNB (0.25%
      bupivacaine) at an outside hospital. The patient underwent immediate angiography
      under sedation. An intra-arterial spasmolysis was performed with alprostadil and
      nitroglycerine and a sufficient perfusion of the glans penis was confirmed.
      Subsequently, systemic sildenafil, arginine, and heparin were given. Following
      this 3-day medical treatment, ischemia resolved completely. Our case emphasizes
      the role of invasive angiography in the diagnostic workup and the therapeutic
      possibilities of local spasmolysis, systemic vasodilatation, and anticoagulation.

PMID- 30276066
TI  - Prevalence and Factors Affecting Cervical Deformity in Adolescent Idiopathic
      Scoliosis Patients: A Single-Center Retrospective Radiological Study.
AB  - Background: It has been reported that adult spinal deformity patients have a high
      prevalence of cervical kyphosis (CK) and cervical positive sagittal malalignment
      (CPSM). However, the prevalence and possible factors affecting CK and CPSM in
      patients with adolescent idiopathic scoliosis (AIS) are less clear. Methods: We
      retrospectively analyzed a consecutive series of AIS patients from a single
      center. Radiographic measurements included the Cobb angle, C2-C7 sagittal
      vertical axis (C2-C7SVA), and C2-C7 lordosis. Cervical deformity was defined as
      loss of lordotic or neutral cervical angle (CK) or C2-C7SVA more than 4 cm
      (CPSM). Patients were stratified by the degree of thoracic kyphosis and coronal
      thoracic curve. Results: A total of 99 patients were included in this study. The
      patients' mean age was 14 years (range, 10-18 years). Mean cervical lordosis and
      C2-C7SVA were 1.5 degrees  and 30.4 mm, respectively. The CK and CPSM prevalence
      were 49% and 16%, respectively, and prevalence of CK and/or CPSM was 59%. CK was
      present in 32% of the patients who had >20 degrees  thoracic kyphosis, and it was
      present in 75% of the patients who had <=20 degrees  thoracic kyphosis (P =
      .003). No association between CPSM and thoracic kyphosis was found. The patients
      who had >20 degrees  coronal thoracic curve had higher CK prevalence (64% versus
      37%, P = .05), but no CPSM association was found. Conclusions: Cervical deformity
      is highly prevalent in AIS patients. There is a significant correlation between
      the loss of thoracic kyphosis and the development of CK but not the development
      of CPSM. High coronal thoracic curve is associated with CK prevalence, but it is
      not associated with CPSM prevalence.

PMID- 30276067
TI  - Facet Sparing Foraminal Decompression Using the Flexible Shaver Foraminotomy
      System: Nerve Safety, Pain Relief, and Patient Satisfaction.
AB  - Background: A number of surgical options exist for decompressing lumbar foraminal
      stenosis. Flexible shaver foraminotomy is a recent addition to this
      armamentarium. While the foraminotomy device has been incorporated into clinical
      practice, the literature on its safety and efficacy remain limited. We aimed to
      evaluate nerve safety, pain relief, and patient satisfaction in a series of
      patients treated with the iO-Flex shaver system (Amendia, Inc., Marietta,
      Georgia). Methods: Thirty-one consecutive patients with lumbar foraminal stenosis
      underwent foraminal decompression using the flexible microblade shaver system at
      62 neuroforamina. The shavers were inserted into each foramen using an open
      hemilaminotomy and fluoroscopic guidance. Nerve mapping via mechanomyography
      (MMG) was used to ensure nerve safety. Perioperative charts were reviewed to find
      the incidence of neurologic complications and to quantify pain relief. Average
      office-based follow-up was 5.3 months. A 3-item questionnaire was administered to
      assess patient satisfaction during late follow-up, which occurred at an average
      of 21 months. Results: No planned iO-Flex foraminotomies were aborted. Neurologic
      complications included transient dysesthetic pain in 1 patient (3.2%, n = 31),
      and transient numbness in 3 patients (9.7%, n = 31). There were no motor
      deficits. The composite nerve complication rate was 12.7%. Preoperative visual
      analog scale scores decreased from a mean of 7.1 (n = 31, standard deviation [SD]
      2.0) to a mean of 3.5 (n = 30, SD 2.5). If asked to repeat their decision to do
      surgery, 81% of patients would redo the procedure. The rate of patient
      dissatisfaction was 19%. Conclusions: Decompression of lumbar foramina using the
      flexible shaver system and MMG nerve mapping is safe and effective, although the
      short-term sensory complication with this technique may be higher than previously
      reported. Patient satisfaction with iO-Flex foraminotomy is comparable to
      reported satisfaction outcomes for traditional lumbar decompression. Level of
      Evidence: 4.

PMID- 30276068
TI  - Endoscopic Transforaminal and Lateral Recess Decompression After Previous Spinal
      Surgery.
AB  - Background: Leg pain and back pain after lumbar laminectomy and spinal
      decompression fusion surgery are common and often related to persistent lumbar
      foraminal or lateral recess stenosis. Although persistent symptoms often stem
      from incomplete decompression during the primary index surgery, recurrent
      symptoms may also be the result of intervertebral cage subsidence due to loss of
      intervertebral and neuroforaminal height. Objective: The aim of this study was to
      investigate the feasibility of using the outpatient transforaminal decompression
      procedure as an alternative to inpatient open procedure in revision decompression
      surgery, with the intent of minimizing the incidence of perioperative and
      postoperative surgical complications while reducing both direct and indirect
      costs of surgical treatment, shortening time to patient postoperative narcotic
      independence, and shortening time of patient return to daily activities. Methods:
      A total of 48 patients with conclusive diagnostic imaging and interventional
      workup underwent endoscopic transforaminal and lateral recess decompression for
      both persistent or recurrent leg and/or low back pain following previous lumbar
      laminectomy (22 patients) or decompression fusion surgery (26 patients). In
      addition to radiographic studies, patients were followed for a minimum of 2 years
      postoperatively, and clinical outcomes were evaluated with the visual analog
      scale (VAS), Oswestry Disability Index (ODI), and modified Macnab criteria.
      Results: At final follow-up, patients with single- and 2-level prior surgeries
      reported an average ODI reduction following their secondary surgery of 44.6%,
      with an average final score of 14.8. Less favorable ODI score reductions
      following secondary surgery (23.8%) were reported by patients who had more than
      one or a complex prior multilevel surgery. According to the modified Macnab
      criteria, "excellent" and "good" results were obtained with the secondary surgery
      in 79.1% (38 of 48) of patients with no more than a single 1- or 2-level prior
      lumbar surgery. The mean VAS score decreased from 7.7 +/- 1.8 preoperatively to
      2.3 +/- 1.1 at final follow-up (P < .01). Fair and poor results with the
      secondary surgery were seen in 20.9% (10 of 48) of patients with several prior
      surgeries or complex multilevel previous lumbar surgeries. The level distribution
      for secondary surgery was as follows: L4-5 segment (26 levels; 54.1%), L5-S1 (14
      levels; 29.2%), L3-4 (7 levels; 14.6%), and the L2-3 level (1 level; 2.1%).
      Postoperative complications were limited to irritation of the dorsal root
      ganglion, which occurred in 25% (12 of 48) of patients. There were no wound
      infections, nerve root injuries, foot drop, or admissions to a hospital for
      further postoperative care. All patients with "excellent" and "good" outcomes
      measured by modified Macnab criteria, who were working before and after the
      primary and secondary surgeries (27 of 38), reported earlier return to work after
      the endoscopic outpatient surgery (2.6 +/- 0.8 weeks) than with the prior
      inpatient open spinal surgery (8.1 +/- 4.5 weeks). Based on the 2012 Medicare fee
      schedule for professional fees, direct costs were 40.6% and indirect costs were
      37.1% lower with the secondary endoscopic surgery compared with primary open
      surgery. Conclusions: Transforaminal decompression is an effective alternative to
      open revision lumbar spinal surgery to treat symptomatic spinal stenosis after
      previous lumbar surgery in patients with persistent or recurrent leg and low back
      pain. It can be safely done in an outpatient setting, while realizing savings in
      direct and indirect costs.

PMID- 30276069
TI  - Computerized Tomography-Based Morphometric Analysis of Subaxial Cervical Spine
      Pedicle in Asymptomatic Indian Population.
AB  - Background: The purpose of this study was to analyze morphometry of the subaxial
      cervical spine pedicles in an Indian population based on computed tomography
      (CT), and thus assess the safety and feasibility of cervical pedicle screw in the
      subaxial cervical spine. Methods: CT scans of 500 subaxial cervical spine
      vertebrae were analyzed from 100 patients presenting to our institution and
      undergoing cervical spine CT scan for an unrelated cause as part of ATLS
      protocol. Pedicle width (PW), pedicle axis length (PAL), pedicle transverse
      angulation (PTA), and lateral pedicle distance (LPD) were calculated on axial CT
      scans, and pedicle height (PH), pedicle length (PL), superior pedicle distance
      (SPD), and pedicle sagittal angulation (PSA) were calculated on sagittal CT
      scans. Results: The mean PW ranged from 4.3 mm at C3 to 5.7 mm at C7. Mean PH
      ranged from 5.5 mm at C3 to 6.1 mm at C7. Mean PTA ranged from 44.5 degrees  at
      C3 to 37.1 degrees  at C7. PSA ranged from 16.65 degrees  at C3 to 3.29 degrees 
      at C7. Mean LPD ranged from 1.6 mm at C3 to 3.4 mm at C6. Mean SPD ranged from
      3.5 mm at C3 to 1.15 mm at C7. Mean PAL ranged from 29.6 mm at C3 to 33.04 mm at
      C7. Mean PL ranged from 5.2 mm at C3 to 5.78 mm at C7. Conclusions: Our CT-based
      morphometric study confirms that cervical pedicle screw placement is possible in
      most of the Indian population except at C3 in females. A thorough understanding
      of pedicle anatomy with proper CT-based preoperative planning can mitigate the
      risk associated with pedicle screw placement in subaxial cervical spine.

PMID- 30276070
TI  - Cervical Myelopathy Secondary to Combined Ossification of Ligamentum Flavum and
      Posterior Longitudinal Ligament-A Case Report.
AB  - In the cervical spine, the combined ossification of the ligamentum flavum (OLF)
      and posterior longitudinal ligament is rarely seen. Patients are usually treated
      with cervical laminectomy or laminoplasty with OLF resection. In most of the
      cases, OLF is adhered to the dura and there is a risk of dural tear or
      cerebrospinal fluid (CSF) leakage during its resection. In this case report, the
      authors present results of laminectomy with debulking instead of complete
      excision of OLF for spinal cord decompression in a cervical myelopathy case in
      which OLF was adhered to the dura. A 69-year-old man presented with insidious
      onset weakness in bilateral lower limbs and unsteady gait, which he had
      experienced 1 month. He has a history of neck pain with left upper limb radiation
      for the last 2 years. Magnetic resonance imaging showed C5-6 severe central canal
      stenosis with underlying myelomalacia. Computed tomography showed ossification
      posterior longitudinal ligament and OLF contributing to severe central canal
      stenosis at the C5-6 level. The patient underwent C4-C6 laminectomy, debulking of
      OLF, posterior instrumentation, and fusion with autogenous bone graft from C3 to
      C6. A histological specimen showed osseous tissue within the ligamentum flavum.
      After surgery the patient's symptoms improved and no recurrence was observed at 4
      years after surgery. The symptoms of myelopathy were successfully treated with
      debulking instead of complete excision of OLF, thus reducing the risk of dural
      tear or CSF leakage.

PMID- 30276071
TI  - Delayed Incisional Hernia Following Minimally Invasive Trans-Psoas Lumbar Spine
      Surgery: Report of a Rare Complication and Management.
AB  - Background: Lateral lumbar interbody fusion (LLIF) has proved to be a safe tool
      in the armamentarium of spine surgeons for a variety of lumbar disorders.
      However, it has some complications related to specific approaches. Incisional
      hernia following abdominal surgery and anterior spinal surgery is commonly
      described; however, it is extremely rare following LLIF, with only 1 case
      reported in short postoperative period. In this report we present the first case
      of delayed presentation of true incisional hernia following a LLIF procedure and
      highlight its presentation, mechanism, possible preventive measures, and
      management. Methods: We report a 57-year-old lady who underwent L3-4 LLIF. She
      presented with vague pain in a healed scar area that had no swelling until two
      years postsurgery, when she developed a painful swelling. On examination, it
      appeared to be a herniation of abdominal contents. Results: She underwent a
      laparoscopic hernia repair surgery. The muscular layers were found to be intact
      with an attenuated transversalis fascia layer. The repair was reinforced by
      polypropylene mesh. There was no recurrence at the 6-month follow-up.
      Conclusions: Incisional hernia can occur following LLIF months to years following
      surgery and can have varied presentation. Tight external oblique closure should
      be performed because the transversalis fascia often cannot be repaired and the
      quality of a layered closure of the deep obliques is often disappointing. The
      treating surgeon should be aware of this complication and aggressively surveil
      for the warning signs, and patients should be counseled about this potential
      complication.

PMID- 30276072
TI  - Early Lumbar Nerve Root Deficit After Three Column Osteotomy for Fixed Sagittal
      Plane Deformities in Adults.
AB  - Background: Three-column osteotomy is an effective means of correcting fixed
      sagittal plane deformities. Deformity correction surgeries may be associated with
      early postoperative neurological deficits often presenting as palsies involving
      the lumbar roots. The objective was to retrospectively assess a subset of our
      series of adult deformity correction surgeries and analyze neurological deficits
      and associated patient and surgical factors. Methods: Hospital records of 17
      patients from a single center were examined. Inclusion criterion were adults (>18
      years) who underwent a 3-column osteotomy (pedicle subtraction osteotomy) at the
      lumbar level for fixed sagittal plane deformities including positive sagittal
      balance, flat back syndrome, and posttraumatic kyphosis. These also included
      cases with associated degenerative lumbar scoliosis. Patients were divided in 2
      groups: Group 1 with lumbar root deficit and Group 2 with no deficits. We
      examined the surgical details of the osteotomy, complications during surgery, and
      observed if the magnitude of correction in the sagittal or coronal plane bore any
      influence on the nerve deficit. Results: All 17 patients had a single-level
      resection except 1 patient who had 2-level osteotomy; 23.5% (4 of 17) developed
      nerve deficit. Nerve deficit presented as bilateral foot drop (1); unilateral
      extensor hallucis longus (EHL) weakness (2); and unilateral quadriceps weakness
      (1). The patient with quadriceps weakness partially recovered to functional
      strength. Two patients with EHL weakness fully recovered; however, the patient
      with bilateral foot drop did not improve. L5-S1 interbody fusion was done in 3 of
      4 cases in Group 1 and 4 of 13 cases in Group 2. Conclusions: Nerve deficits
      after 3-column corrective osteotomies occurred in 23% cases. All but 1 case had
      significant improvement. Most nerve palsies are neuropraxia and unilateral and
      tend to recover. L5 weakness appears most common after high lumbar osteotomies.
      Significant correction of scoliosis at the osteotomy level (>50%) may be a reason
      for nerve palsy.

PMID- 30276073
TI  - Factors Affecting Utilization of Steroid Injections in the Treatment of
      Lumbosacral Degenerative Conditions in the United States.
AB  - Background: Lumbar degenerative conditions are an extremely common set of
      diagnoses with a large spectrum of treatment options. Epidural steroid injections
      (ESI) are widely used but have come under increased scrutiny as we move toward a
      value-based model of health care. We assessed current utilization of epidural
      steroid injections, changes in utilization over time, and the influence of payer
      type and geographic region within the United States on their utilization. In
      addition, we analyzed the relationship between ESIs and surgical rates across
      states. Methods: The Medicare 5% national sample administrative database (SAF5)
      and a large national database from a commercial health care company (HORTHO) were
      used to catalog clinical data for patients with lumbar degenerative conditions.
      Specific queries into the rate of ESIs and lumbar surgery were also performed
      within this group. Results: There were 4 108 121 patients found between 2005 and
      2015 in the SAF5 and HORTHO databases carrying a diagnosis related to lumbar
      degenerative conditions. The overall yearly injection rates for patients with
      lumbar degenerative conditions ranged from 9.84% to 10.18%. In patients older
      than 65, the rate of ESI was higher for Medicare as compared with private payer
      insurance (16.27% versus 14.14%, P < .001). There was a higher rate of ESI for
      patients who eventually underwent surgery in the Medicare group as compared with
      the commercial group (55.30% versus 40.40%, P < .001). There was a positive
      correlation between rates of ESI with the rate of surgery between states.
      Conclusions: There is considerable variation in treatment of lumbar degenerative
      conditions with ESI based on payer type. There was increased utilization of
      lumbar ESI between 2007 and 2012, although this change was less than 0.5%. The
      data also suggest a positive correlation between rates of ESIs and surgical
      intervention across states. This points to areas in the country with high
      utilization of both ESI and surgery in the treatment of lumbar degenerative
      conditions. Level of Evidence: III, economic and decision analysis.

PMID- 30276074
TI  - Clinical Outcomes of Single-Level Anterior Cervical Discectomy and Fusion.
AB  - Background: The purpose of the present study was to determine the differences in
      health outcomes between patients with cervical spondylosis who underwent single
      level anterior cervical discectomy and fusion (ACDF) and patients with cervical
      spondylosis who did not undergo an ACDF fusion (non-ACDF). The hypothesis of the
      study was that patients undergoing single-level fusion have a lower risk of
      downstream cardiovascular disease and depression. Methods: The Medicare 5% sample
      was used to identify patients who received a diagnosis of spondylosis during 2005
      2012. All spondylosis patients were separated into nonoperative and operative
      groups. Differences in new disease diagnoses, age, sex, and Charlson Comorbidity
      Index (CCI) scores were recorded. Results: The relative risk (RR) of heart
      failure was lower in the ACDF group after 3 years (RR = 0.6719; P < .05), 5 years
      (RR = 0.8477; P = 1.17), and 7 years (RR = 0.7709; P = 1.625). The RR of
      depression was higher in the ACDF group at 1 year (RR = 2.5008), 3 years (RR =
      1.4473), 5 years (RR = 2.2625), and 7 years (RR = 2.2257; P < .05 for all). Mean
      CCI score of patients before undergoing ACDF was 10 (SD, 9.20), whereas the mean
      score after surgery was 8 (SD, 7.84; P < .05), and the score for non-ACDF
      patients remained unchanged at a CCI of 10 (SD, 9.00; P < .05). Conclusions: The
      results demonstrate the patients in the ACDF cohort have an increased RR of
      depression but a decreased risk of cardiovascular disease. Further research may
      be needed to delineate why the ACDF procedure potentially benefits a patient for
      heart disease but may stress a patient's social/economic supports during the
      recovery process, thus leading to higher depression rates for patients undergoing
      ACDF.

PMID- 30276075
TI  - The Use of Magnetic Resonance Imaging and Plain Radiographs Among Adolescents
      With Back Pain and Adolescent Idiopathic Scoliosis.
AB  - Background: Low back pain (LBP) and adolescent idiopathic scoliosis (AIS) are
      common pediatric diagnoses. The workup for these diagnoses can be highly variable
      and can use significant health care resources. There has been no analysis to date
      on the use of imaging for workup of AIS and/or LBP. Methods: The Humana Private
      Payer Database was queried for clinical and financial information for patients
      with AIS and/or LBP using International Classification of Diseases (ICD-9) for
      LBP and AIS. Current procedural terminology codes related to magnetic resonance
      imaging (MRI) and radiographs for the thoracolumbar spine were used to identify
      patients with LBP and/or AIS that used these diagnostic imaging modalities. Only
      patients ages 10 to 19 years were included in this analysis. Results: The total
      number of patients with AIS and LBP was 18 696 and 56 560, respectively.
      Thoracolumbar imaging was used within the workup for 71.76% and 45.53% of
      patients with AIS alone and LBP alone, respectively. MRI was used for 2.92% and
      9.53% of patients with AIS alone and LBP alone, respectively. Radiographic
      imaging was used for 71.06% and 42.63% for AIS alone and LBP alone, respectively.
      There was minimal variation among regions in use of MRI for AIS. For patients
      with LBP, the diagnosis with the highest use of MRI was "sciatica" (29.07%).
      Patients with both LBP and AIS had statistically higher rates of imaging
      (91.04%), MRI (18.99%), and radiographs (89.71%). Among patients with an MRI,
      20.87% never had a radiograph. Reimbursement per patient for radiographs was $164
      and $239 for AIS and LBP, respectively. Reimbursement per patient for MRI was
      $1,263 and $1,882 for AIS and LBP, respectively. Conclusions: There is
      substantial use of both MRI and radiographs for adolescents with LBP and/or AIS.
      Clinicians should be aware of the impact these diagnostic tests have on the
      patient and the overall health care system.

PMID- 30276076
TI  - Middle-Column Gap Balancing and Middle-Column Mismatch in Spinal Reconstructive
      Surgery.
AB  - Background: Middle-column gap balancing (MCGB) is a reference measurement of the
      path of the posterior longitudinal ligament (PLL), which is reconstructed under
      tension and balanced by the combined height of the posterior one-third of the
      vertebral bodies and the posterior one-third of the disks, including any
      intervening load-sharing spacers. This measurement allows for a comparison of the
      ligamentous component of the middle column (PLL) with the load-sharing components
      (posterior one-third vertebral body + disk ). This difference gives rise to a
      "middle-column mismatch," which provides a linear measurement of the redundancy
      of the ligaments and neural elements, which relates to the correct cage, spacer,
      or load-bearing height, which is optimized. Methods: For phase 1 measurement
      testing, 24 consecutive patients underwent reliable flexion, extension, and
      neutral lateral radiographic studies with a calibrated marker. The anterior,
      middle, and posterior columns were measured using a custom software program
      capable of measuring the length of curved lines specifically written for this
      purpose. For phase 2 measurement testing, 21 consecutive patients undergoing
      surgery with multilevel deformities for cervical, thoracic, and lumbar procedures
      had MCGB height pre- and postoperatively measured by 3 blinded observers. The
      preoperative and postoperative measurements were compared using a linear
      regression analysis and Pearson product-moment correlation. Results: In phase 1
      measurement testing the flexion, extension, and neutral bending radiographs of
      spinal segments not containing deformities showed that the middle column had the
      most reliable measurements of spinal axial height both in the actual measurements
      of change from flexion to extension (mm) and in percentage of change. In phase 2
      measurement testing, a Pearson product-moment correlation was run between each
      individual's pre- and postoperative middle-column measurements. There was a
      strong positive correlation between preoperative and postoperative measurements,
      which was statistically significant (r = 0.983, n = 21, P < .01). Conclusions:
      This consecutive series of 21 deformity patients demonstrated the utility of
      measuring the preoperative middle-column length in predicting the optimal height
      of the spacers and intervertebral disks, and posterior vertebral body height,
      simultaneously restoring sagittal and coronal plane alignment. Key points of this
      study include the following: (1) Spinal balance requires optimizing spinal
      height, which is a curved line in order to accommodate cervical lordosis,
      thoracic kyphosis, and lumbar lordosis. (2) Software programs can allow
      measurement of the preoperative curved circuitous course of the PLL and vertebral
      body misalignment; this curved length is predictive of the optimal postoperative
      middle-column height after spinal osteotomies and intervertebral spacer
      insertion. (3) All 3 dimensions are important to optimize in deformity
      correction: sagittal plane, coronal plane, and axial spinal height.

PMID- 30276078
TI  - Lumbar Lordosis Correction With Interbody Hyperlordotic Cages: Initial
      Experience, Learning Curve, Technical Aspects, and Complication Incidence.
AB  - Background: Analysis of the initial experience on learning curve, technical
      differences and perioperative or early postoperative complications using lumbar
      hyperlordotic anterior and lateral interbody cages for the correction of lumbar
      lordosis as compared with the usage of regular lordotic cages. Methods: Initial
      21 consecutive patients were treated with 13 hyperlordotic anterior lumbar
      interbody fusion (ALIF) cages and 8 hyperlordotic extreme lateral interbody
      fusion (XLIF) cages. The mean patient age was 64 years, and the mean lumbar
      hypolordosis was 23 degrees . Results: No significant procedure-related technical
      differences were found between the hyperlordotic and nonhyperlordotic ALIF cages.
      Slightly significant procedure-related technical differences were found between
      hyperlordotic and nonhyperlordotic XLIF cages. The complication type and
      occurrence were comparable. Conclusions: Sagittal balance correction of lumbar
      lordosis using hyperlordotic ALIF and XLIF cages is a relatively safe surgical
      procedure with a short learning curve for those surgeons already familiar with
      anterior and lateral retroperitoneal procedures.

PMID- 30276077
TI  - Anterior and Lateral Lumbar Interbody Fusion With Supplemental Interspinous
      Process Fixation: Outcomes from a Multicenter, Prospective, Randomized,
      Controlled Study.
AB  - Background: Rigid interspinous process fixation (ISPF) has received consideration
      as an efficient, minimally disruptive technique in supporting lumbar interbody
      fusion. However, despite advantageous intraoperative utility, limited evidence
      exists characterizing midterm to long-term clinical outcomes with ISPF. The
      objective of this multicenter study was to prospectively assess patients
      receiving single-level anterior (ALIF) or lateral (LLIF) lumbar interbody fusion
      with adjunctive ISPF. Methods: This was a prospective, randomized, multicenter
      (11 investigators), noninferiority trial. All patients received single-level ALIF
      or LLIF with supplemental ISPF (n = 66) or pedicle screw fixation (PSF; n = 37)
      for degenerative disc disease and/or spondylolisthesis (grade <=2). The
      randomization patient ratio was 2:1, ISPF/PSF. Perioperative and follow-up
      outcomes were collected (6 weeks, 3 months, 6 months, and 12 months). Results:
      For ISPF patients, mean posterior intraoperative outcomes were: blood loss, 70.9
      mL; operating time, 52.2 minutes; incision length, 5.5 cm; and fluoroscopic
      imaging time, 10.4 seconds. Statistically significant improvement in patient
      Oswestry Disability Index scores were achieved by just 6 weeks after operation (P
      < .01) and improved out to 12 months for the ISPF cohort. Patient-reported 36
      Item Short Form Health Survey and Zurich Claudication Questionnaire scores were
      also significantly improved from baseline to 12 months in the ISPF cohort (P <
      .01). A total of 92.7% of ISPF patients exhibited interspinous fusion at 12
      months. One ISPF patient (1.5%) required a secondary surgical intervention of
      possible relation to the posterior instrumentation/procedure. Conclusion: ISPF
      can be achieved quickly, with minimal tissue disruption and complication. In
      supplementing ALIF and LLIF, ISPF supported significant improvement in early
      postoperative (<=12 months) patient-reported outcomes, while facilitating robust
      posterior fusion.

PMID- 30276079
TI  - Polyetheretherketone (PEEK) Rods for Lumbar Fusion: A Systematic Review and Meta
      Analysis.
AB  - Background: The purpose of this systematic review is to evaluate the safety and
      effectiveness of polyetheretherketone (PEEK) rod systems in patients receiving
      lumbar interbody fusion treatment. Meta-analyses of relevant clinical data were
      also conducted when possible. Methods: Relevant studies were identified by
      searching the PubMed, EMBASE, and Cochrane Library databases. Clinical studies
      evaluating the safety and/or effectiveness of the PEEK rod spinal stabilization
      system in patients receiving lumbar spinal fusion procedure were included.
      Studies regarding dynamic stabilization and hybrid stabilization (fixed and
      dynamic; eg, topping-off technique) were not included in this analysis. The
      analyses included patients who had a lumbar fusion procedure with PEEK rods or
      titanium rods as a control reference (only for controlled studies). Fusion
      success, functional and pain improvement, and safety data were evaluated, if
      reported. Results: The search yielded 5 studies (1 prospective and 4
      retrospectives) that included 177 participants (156 received PEEK rods, and 21
      received titanium rods). Meta-analysis of interbody fusion success rate in PEEK
      rod patients yields the estimate of 95.6% (confidence interval: 91.6% to 98.4%).
      Functional outcomes in PEEK rod patients demonstrated clinically significant
      improvement when comparing postoperative to preoperative scores, with an average
      improvement of 67.4% +/- 8.5%. Similarly, pain improvement was clinically
      significant with an average visual analog scores-back pain and visual analog
      scores-leg pain improvement percentages of 68.9% +/- 8.6% and 76.6% +/- 1.5%,
      respectively. Rod fracture was not reported in any of the studies. The rates of
      screw fracture and loosening were 3/114 (2.6%) and 1/50 (2.0%), respectively. In
      the controlled study, no statistically significant difference was reported in the
      fusion success rate, function improvement, pain improvement, or device-related
      events between subjects treated with PEEK rods and the subjects treated with
      titanium rods. Conclusions: Experience with PEEK rod systems has shown
      satisfactory clinical outcomes. Therefore, these results support the use of PEEK
      rod systems as supplemental fixation during lumbar fusion procedures.

PMID- 30276081
TI  - Feasibility of Endoscopic Inspection of Pedicle Wall Integrity in a Live Surgery
      Model.
AB  - Background: Perforations of the pedicle wall during cannulation can occur with
      experienced surgeons. Direct endoscopic visualization has not been used to
      inspect pedicles previously due to bone bleeding obscuring the camera
      visualization. The hypothesis of this study was that endoscopic visualization of
      pedicle wall integrity was technically feasible and would enable identification
      of clinically significant pedicle breaches. Methods: A live porcine model was
      used. Eight lumbar pedicles were cannulated. Clinically significant breaches were
      created. An endoscope was introduced and was used to inspect the pedicles.
      Results: All lumbar pedicles were endoscopically visible at a systolic pressure
      of 100 mm Hg. Clinically relevant anatomic structures and iatrogenic pathology,
      such as medial, lateral, and anterior breaches, were identified. There were no
      untoward events resulting from endoscopic inspection of the pedicle endosteal
      canal. Conclusions: Endoscopic inspection of lumbar pedicles was safe and
      effective. The findings on endoscopic inspection corresponded with the ball-tip
      probe palpation techniques. Additional techniques, such as selection between 2
      tracts, was possible with the endoscopic technique.

PMID- 30276082
TI  - Trends in Nonoperative Treatment Modalities Prior to Cervical Surgery and Impact
      on Patient-Derived Outcomes: Two-Year Analysis of 1522 Patients From the
      Prospective Spine Treatment Outcome Study.
AB  - Background: Effects of nonoperative treatments on surgical outcomes for patients
      who failed conservative management for cervical spine pathologies remain unknown.
      The objective is to describe conservative modality use in patients indicated for
      surgery for degenerative cervical spine conditions and its impact on
      perioperative outcomes. Methods: The current study comprises a retrospective
      review of a prospective multicenter database. A total of 1522 patients with 1- to
      2-level degenerative cervical pathology who were undergoing surgical intervention
      were included. Outcome measures used were health-related quality-of-life scores,
      length of hospitalization, estimated blood loss, length of surgery, and return-to
      work status at 2 weeks, 6 months, 1 year, and 2 years postoperatively. Patients
      were grouped by diagnosis (radiculopathy vs. myelopathy), then divided based on
      epidural injection(s), physical therapy (PT), or opioid use prior to enrollment.
      Univariate t-tests and chi2 tests were performed to determine differences between
      groups and impact on outcomes. Results: Among 1319 radiculopathy patients, 25.7%
      received preoperative epidural injections, 35.3% received PT, and 35.5% received
      opioids. Radiculopathy patients who received epidurals and PT had higher 1-year
      postoperative return-to-work rates (P < .05). Radiculopathy patients without
      preoperative PT had longer hospitalization times, whereas those who received PT
      had higher 36-Item Short Form Health Survey (SF-36) physical functioning and
      physical component scores, lower 2-year visual analog scale (VAS) neck/arm pain
      scores, and higher 2-year return-to-work incidence (P < .05). Of myelopathy
      patients (n = 203), 14.8% received epidural injections, 25.1% received opioids,
      and 41.5% received PT. Myelopathy patients with preoperative PT had worse VAS arm
      pain scores 2 years postoperatively (P < .05). Patients receiving opioids were
      younger and had greater baseline-2-year Neck Disability Index improvement (P <
      .05). Conclusions: Radiculopathy patients receiving epidurals returned to work
      after 1 year more frequently. PT was associated with shorter hospitalizations,
      greater SF-36 bodily pain norm and physical component score improvements, and
      increased return-to-work rates after 1 and 2 years. No statistically significant
      nonoperative treatment was associated with return-to-work rate in myelopathy
      patients. Clinical Relevance: These findings suggest certain preoperative
      conservative treatment modalities are associated with improved outcomes in
      radiculopathy patients.

PMID- 30276083
TI  - Risk of Cancer Following Lumbar Fusion Surgery With Recombinant Human Bone
      Morphogenic Protein-2 (rhBMP-2): An Analysis Using a Commercially Insured Patient
      Population.
AB  - Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is
      frequently used to promote new bone growth after lumbar fusion surgery. However,
      because BMP receptors are found on cancer cells, there is concern about potential
      cancer following treatment with rhBMP-2. Data from clinical trials have reported
      divergent results and have been limited by small sample sizes and relatively
      short follow-up. We therefore examined the long-term risk of cancer following
      treatment with rhBMP-2 after lumbar fusion surgery. Methods: Using the MarketScan
      Commercial Claims and Encounters database, we identified all patients <65 years
      without prior cancer who underwent lumbar fusion surgery between October 2003 and
      December 2009 and were followed at least 3 years after surgery. Development of
      any Surveillance Epidemiology and End Results malignancy in follow-up was
      identified through diagnosis and procedure codes. Results: Among 39 448 eligible
      patients, 2345 (5.9%) received rhBMP at surgery; the median follow-up in this
      population was 4.87 years. Cancer in follow-up was observed in 49 BMP-treated
      patients (0.43/100 person years) and 1072 nontreated patients (0.58/100 person
      years). Use of rhBMP was associated with a cancer risk similar to that of
      untreated patients in both univariate (hazard ratio, 0.80; 95%, CI 0.54-1.19) and
      multivariate proportional hazards analyses (hazard ratio, 0.81; 95% CI, 0.54
      1.20). Similar findings were observed in a secondary analysis after adjustment
      for likelihood of rhBMP administration. Conclusions: In this retrospective cohort
      with at least 3 years of follow-up, administration of rhBMP during lumbar fusion
      surgery was not associated with an increased risk of subsequent cancer. Level of
      Evidence: 4.

PMID- 30276084
TI  - Relationship of Cervical Sagittal Vertical Alignment After Sagittal Balance
      Correction in Adult Spinal Deformity: A Retrospective Radiographic Study.
AB  - Study Design: Retrospective radiographic study. Purpose: Predict the variability
      of the center of gravity of head (COG) relative to the global cervical sagittal
      alignment (SVA). Background: Cervical lordosis, thoracic kyphosis, lumbar
      lordosis, and pelvic incidence are considered interrelated, with changes in SVA
      causing reciprocal changes to bring the head over pelvis. The implications of
      cervical deformities have generated more interest recently, and it has been shown
      that poor cervical alignment is associated with poor clinical outcomes. Methods:
      Patients were selected from the imaging server of a single institution with adult
      spinal deformity (ASD) and SVA, who underwent surgical correction from 2008 to
      2013. Three observers performed the measurements, and intraclass correlation
      coefficient (ICC) was measured for inter and intraobserver reliability. Group 1
      was patients with unbalanced spines (C7-SVA > 5 cm) preoperatively and corrected
      to full balanced spine (C7-SVA < 5 cm) until last follow-up. Group 2 was improved
      in sagittal balance after surgery and maintained SVA correction until last follow
      up, but not fully balanced. Results: Fifty-five patients met the inclusion
      criteria, 42 patients improved in SVA after surgery, and 13 showed no
      improvement. Twenty-three patients kept full balanced measurements until last
      follow-up, and 19 patients maintained not-full balanced spine. In group 1, there
      was no change in pre and postoperative parameters except for C2-CL (21.74 degrees
      vs 16.91 degrees , P = .033). It was similar in group 2, no differences except
      for C2-CL (21.67 degrees  vs 17.81 degrees , P = .018). Conclusion: Parameters in
      this study failed to yield predictable relationships when compared to changes in
      SVA. The position of COG may be independent of global SVA. Clinical Relevance:
      This study aims to improve our understanding of the dynamic changes and
      relationships of the regional and global spinal parameters with regard to spinal
      deformity corrective surgeries in adults. Level of Evidence: III.

PMID- 30276085
TI  - Rates of Mortality in Cervical Spine Surgical Procedures and Factors Associated
      With Its Occurrence Over a 10-Year Period: A Study of 342 477 Patients on the
      Nationwide Inpatient Sample.
AB  - Background: Risk of death is important in counseling patients and improving
      quality of care. Incidence of death in cervical surgery is not firmly established
      due to its rarity and limited sample sizes, particularly in the context of
      different surgeries, demographics, and risk factors. Particularly, different
      patient risk profiles may have varying degrees of risk in terms of surgeries,
      comorbidities, and demographics. This study aims to use a large patient cohort
      available on a national database to study the prevalence of death associated with
      cervical spine surgery. Methods: This study was a retrospective review of the
      Nationwide Inpatient Sample (NIS) years 2003-2012. A total of 342 477 patients
      were identified by International Classification of Diseases, Ninth Revision,
      Clinical Modification codes undergoing spinal fusion or decompression for disc
      degeneration, stenosis, spondylosis, myelopathy, postlaminectomy syndrome,
      scoliosis, or neck pain associated with the cervical region. Patients with
      malignancy were excluded from analysis. Incidence of mortality was assessed by
      chi2 tests across different patient demographics and comorbidities, procedures
      performed, and concurrent in-hospital complications. Binary logistic regression
      identified significant increases or decreases in risk of death while controlling
      for comorbidities, race, sex, and Mirza invasiveness. Significance was defined as
      P < .05 differences relative to overall cohort. Results: The study analyzed 342
      477 patients with an overall mortality rate of 0.32%. A total of 231 977 simple
      fusions (single approach and <3 levels) experienced a mortality rate of 0.256%;
      49 594 complex fusions (combined approach or >=3 levels) had a mortality rate of
      0.534%; and 61 285 decompression-only procedures reported a 0.424% mortality
      rate, all P < .001 from overall rate. In reporting rates across different
      demographics, male patients experienced a significantly higher risk for mortality
      (odds ratio [OR], 2.16; 95% CI, 1.87-4.49), as did black patients (OR, 1.58; CI,
      1.32-1.90) and patients over age 75 (OR, 7.55; 95% CI, 6.58-8.65), all P < .001.
      Patients with liver disease reported 6.40% mortality. Similarly, patients with
      congestive heart failure (3.91%), cerebrovascular disease (3.41%), and paraplegia
      (3.79%) experienced high mortality rates, all in cohorts of over 2000 patients,
      all P < .001. Concurrent in-hospital complications with the highest risk of
      mortality were shock (OR, 51.41; 95% CI, 24.08-109.76), pulmonary embolism (OR,
      25.01; 95% CI, 14.70-42.56), and adult respiratory distress disorder (OR, 14.94;
      95% CI, 12.75-17.52), all P < .001. Conclusion: In 342 477 cervical spine surgery
      patients an overall mortality rate of 0.32% was reported. The rate was 3.91% in a
      cohort of 5933 patients with congestive heart failure and 3.79% in a cohort of
      6947 patients with paraplegia. These findings are consistent with previous
      estimates and may help counsel patients and improve in-hospital safety. Level of
      Evidence: 3.

PMID- 30276086
TI  - Does Resection of the Posterior Longitudinal Ligament Affect the Stability of
      Cervical Disc Arthroplasty?
AB  - Background: The need for posterior longitudinal ligament (PLL) resection during
      cervical total disc arthroplasty (TDA) has been debated. The purpose of this
      laboratory study was to investigate the effect of PLL resection on cervical
      kinematics after TDA. Methods: Eight cadaveric cervical spine specimens were
      tested in flexion-extension (FE), lateral bending (LB), and axial rotation (AR)
      to moments of +/-1.5 Nm. After testing the intact condition, anterior C5-C6
      cervical discectomy was performed followed by PLL resection and implantation of a
      compressible, 6-degrees-of-freedom disc prosthesis (M6-C, Spinal Kinetics Inc,
      Sunnyvale, California). Next, a second prosthesis was implanted at C6-C7 with PLL
      intact. Finally, the C6-C7 PLL was resected while the disc prosthesis remained in
      place. Segmental range of motion (ROM) and stiffness in the high flexibility zone
      around the neutral posture were analyzed using repeated measures ANOVA. Results:
      At C5-C6, following TDA and PLL resection, FE, LB, and AR ROMs decreased
      significantly. Anterior and posterior disc height, segmental lordosis, and
      flexion stiffness increased significantly. At C6-C7, TDA with the PLL intact
      resulted in a significant increase in anterior disc height and segmental lordosis
      with no change in posterior disc height. FE, LB, and AR ROMs all decreased
      significantly, while flexion stiffness increased significantly compared to
      intact. PLL resection at C6-C7 did not result in a notable change compared to TDA
      with PLL intact. At the same level, flexion stiffness decreased following PLL
      resection compared to TDA with a value closer to intact. Two-level TDA (C5-C7)
      with PLL resection did not result in a loss of segmental stability. Conclusion:
      PLL resection did not significantly affect motion segment kinematics following
      cervical TDA using a prosthesis with inherent stiffness. Motion segment stiffness
      loss after PLL resection can be compensated for by a TDA design that can provide
      resistance to angular motion.

PMID- 30276087
TI  - Review of Vertebral Augmentation: An Updated Meta-analysis of the Effectiveness.
AB  - Background: To update vertebral augmentation literature by comparing outcomes
      between vertebroplasty (VP), balloon kyphoplasty (BKP), vertebral augmentation
      with implant (VAI), and nonsurgical management (NSM) for treating vertebral
      compression fractures (VCFs). Methods: A PubMed literature search was conducted
      with keywords kyphoplasty, vertebroplasty, vertebral body stent, and vertebral
      augmentation AND implant for English-language articles from February 1, 2011, to
      November 22, 2016. Among the results, 25 met the inclusion criteria for the meta
      analysis. Inclusion criteria were prospective comparative studies for mid-/lower
      thoracic and lumbar VCFs enrolling at least 20 patients. Exclusion criteria
      included studies that were single arm, systematic reviews and meta-analyses,
      traumatic nonosteoporotic or cancer-related fractures, lack of clinical outcomes,
      or non-Level I and non-Level II studies. Standardized mean difference between
      baseline and end point for each outcome was calculated, and treatment groups were
      pooled using random effects meta-analysis. Results: Visual analog scale pain
      reduction for BKP and VP was -4.05 and -3.88, respectively. VP was better than
      but not significantly different from NSM (-2.66), yet BKP showed significant
      improvement from both NSM and VAI (-2.77). The Oswestry Disability Index
      reduction for BKP showed a significant improvement over VAI (P < .001). There was
      no significant difference in changes between BKP and VP for anterior (P = .226)
      and posterior (P = .293) vertebral height restoration. There was no significant
      difference in subsequent fractures following BKP (32.7%; 95% confidence interval
      [CI]: 8.8%-56.6%) or VP (28.3%; 95% CI: 7.0%-49.7%) compared with NSM (15.9%; 95%
      CI: 5.2%-26.6%). Conclusions/Level of Evidence: Based on Level I and II studies,
      BKP had significantly better and VP tended to have better pain reduction compared
      with NSM. BKP tended to have better height restoration than VP. Additionally, BKP
      had significant improvements in pain reduction and disability score as compared
      with VAI. Clinical Relevance: This meta-analysis serves to further define and
      support the safety and efficacy of vertebral augmentation.

PMID- 30276088
TI  - Anterior Lumbar Interbody Fusion With Cement Augmentation Without Posterior
      Fixation to Treat Isthmic Spondylolisthesis in an Osteopenic Patient-A Surgical
      Technique.
AB  - Background: Anterior lumbar interbody fusion (ALIF) has been well established as
      an effective surgical intervention for chronic back pain due to osteoporotic
      vertebral collapse. Historically, ALIF has consisted of an anterior approach to
      disc height restoration with a subsequent posterior pedicle screw fixation.
      Although the applications of cement augmentation with posterior fixation have
      been previously reported, treatment of patients with both isthmic
      spondylolisthesis and decreased bone mineral density using a stand-alone ALIF is
      controversial because of concerns for decreased fusion rates and increased
      subsidence risk, respectively. We report a case of stand-alone ALIF used to treat
      a low-grade isthmic spondylolisthesis in the setting of idiopathic thoraco-lumbar
      scoliosis in a patient with secondary degenerative changes and discuss the
      benefits of this surgical technique in a patient with several comorbidities.
      Methods: An osteopenic 66-year-old woman with multiple medical comorbidities and
      2 years of left radicular leg pain was found to have a Myerding grade I isthmic
      spondylolisthesis in the setting of idiopathic thoraco-lumbar scoliosis with
      secondary changes. The patient underwent an L5-S1 stand-alone ALIF with anterior
      cement augmentation without posterior pedicle screw fixation. Results: The
      patient experienced immediate relief of radicular leg pain postoperatively and
      had an uneventful course. At 2 years follow-up, she remained symptom free, and
      radiographs showed excellent fusion and maintenance of intervertebral disc
      height. Conclusions: The use of stand-alone ALIF with anterior cement
      augmentation of the vertebral bodies is a surgical technique that could produce
      excellent improvement in patients with low-grade isthmic spondylolisthesis in the
      setting of osteopenia. The use of the all-anterior approach in similar patients
      with multiple medical comorbidities can also be a useful technique, as it
      decreases associated morbidity of surgery and complication risks associated with
      prolonged operative times.

PMID- 30276089
TI  - Combined Aorto-Iliac and Anterior Lumbar Spine Reconstruction: A Case Series.
AB  - Background: Treatment options for aortic-iliac pathology may include endovascular
      repair and open surgical repair. Treatment options for degenerative disc disease
      (DDD) are varied but commonly include anterior reconstruction. When both the
      aortic-iliac and spinal pathologies are significant and surgical intervention is
      indicated for each pathology, the opportunity exists for concurrent treatment of
      both the aortic-iliac pathology and DDD in the same operation. The purpose of
      this case series was to document the safety and feasibility of a surgical
      strategy whereby a combined elective reconstructive procedure was performed for
      aortic and anterior lumbar spinal pathologies. Methods: The case histories of 5
      patients who were treated for both spinal and vascular pathology are presented.
      Surgical outcome measures included operative time, blood loss, length of stay,
      and complications. Spine-specific outcome measures included Oswestry Disability
      Index, Roland Morris Disability Questionnaire, and visual analogue scores (back
      and leg). Results: The spinal reconstructions performed included 1 L4-5 total
      disc replacement (TDR), 1 L4-5, L5-S1 anterior lumbar interbody fusion (ALIF), 1
      L5-S1 ALIF, and 2 hybrid procedures (L4-5 TDR with L5-S1 ALIF). Vascular
      reconstructions included 4 aorto-bi-iliac bypass grafts and 1 aortic tube graft.
      The average operative time was 365 minutes (ranging between 330 and 510 minutes),
      the average blood loss was 1699 mL (range between 1160 and 2960 mL), and the
      average length of hospital stay was 14 days (range from 8 to 22 days). There were
      no in-hospital complications, and all patients experienced significant
      improvement in both back and leg pain. One patient developed kinking of the iliac
      limbs of the vascular graft 1 year postoperatively, which was managed with
      endovascular stenting of the graft. Conclusions: Aortic-iliac pathology and DDD
      are significant pathologies often treated in isolation. This study illustrates
      that, despite its complexity, highly trained individuals in a specialized setting
      can perform combined surgery to achieve a satisfactory outcome for the patient.
      Level of Evidence: Level IV evidence.

PMID- 30276090
TI  - Ligamentum Flavum Hematoma Presented with Low Back Pain: A Case Report and Review
      of the Literature.
AB  - A 61-year-old woman with no past medical history presented with low back pain and
      radicular pain in the right lower extremity. Magnetic resonance imaging of the
      lumbar spine showed a heterogeneous intensity mass in the lateral recess of the
      spinal canal at the L4-5 disk level. Postoperatively, her radicular pain resolved
      within a few days with excellent low back pain relief. Ligamentum flavum hematoma
      is a rare differential diagnosis for cystic lesions in the lumbar spine that can
      be removed simply by surgery with excellent relief of symptoms and improvement in
      strength of the right lower extremity and increased sensitivity.

PMID- 30276091
TI  - Readmissions After Outpatient Transforaminal Decompression for Lumbar Foraminal
      and Lateral Recess Stenosis.
AB  - Background: The objective of this study was to analyze readmission rates after
      outpatient transforaminal endoscopic decompression surgery for lumbar foraminal
      and lateral recess stenosis done in an ambulatory surgery center. Endoscopic
      lumbar spinal surgery is gaining popularity for the treatment of lumbar disc
      herniations. Recent advances in surgical techniques allow for percutaneous
      endoscopically assisted bony decompression for neurogenic claudication symptoms
      due to spinal stenosis. The surgery can be done under local anesthesia and
      sedation. Patients may be discharged home within hours from surgery, and
      complications are rare. However, readmissions for recurrent disc herniations,
      failure of pain relief, dysesthetic leg pain, nerve root injuries with foot drop,
      and facet and pedicle fractures have been reported. Methods: A retrospective
      study of 1839 consecutive patients with an average mean follow up of 33 months
      (range 24 to 85 months) that underwent percutaneous endoscopic surgery at 2076
      levels between 2006 and 2015 was conducted with the intent of identifying factors
      associated with emergency room or hospital readmission following endoscopic
      foraminotomy and microdiscectomy. Only patients with unilateral radiculopathy due
      to either herniated disc or lateral recess stenosis were included in this study.
      Preoperatively, disc migration was graded by direction and distance from the disc
      space according to Lee's radiologic 4-zone classification. The type of disc
      herniation was classified either as extruded or contained. Contained herniations
      were further subclassified as disc protrusions versus disc bulges. In addition,
      the preoperative disc height was recorded. Bony spinal foraminal stenosis and
      lateral recess stenosis were graded on preoperative magnetic resonance imaging
      and computed tomography scans into mild, moderate, and severe by dividing the
      lumbar neuroforamen into 3 zones: (a) entry zone, (b) midzone, and (c) exit zone.
      Surgical outcomes were classified according to the Macnab criteria. In addition,
      reduction in visual analog scores (VASs) were assessed. The treating physician
      (KUL) performed all surgeries. Results: According to the Macnab criteria,
      excellent and good results were obtained in 82.2% of patients with extruded disc
      fragment (331/1839). In this group, the mean VAS decreased from 5.9 +/- 2.5
      preoperatively to 2.4 +/- 1.8 at the final follow up (P < .01). Patients with
      contained disc herniations (648/1839) had excellent and good results 72.7% of the
      time. In this group, the mean VAS decreased from 7.2 +/- 1.6 preoperatively to
      3.1 +/- 1.5 at the final follow up (P < .01). In the spinal stenosis group
      (860/1839), 75% of patients had excellent to good results. There were no major
      approach-related complications. Sixty-nine patients had extravasations of
      irrigation fluid into the subcutaneous tissues (3.8%). Eight patients developed
      spinal headaches (0.4%). Two patients developed foot drop on the surgical side
      immediately postoperatively (0.1%). Reherniations of extruded discs occurred in 9
      patients (2.7% recurrence rate). Failure of pain relief without significant
      improvement of walking endurance occurred in 29 patients with bony stenosis in
      the central canal, lateral recess, and entry zone of the neuroforamen (3.3%).
      Reherniations were associated with preserved disc height of >6 mm (P < .02).
      Dysesthetic leg pain due to dorsal root ganglion irritation occurred in 229
      patients (12.4%) and was unrelated to case frequency but was associated with
      severe foraminal stenosis (P < .01). All 229 patients improved with supportive
      care. Facet or pedicle fractures did not occur in this series. There were 26
      acute care (within 6 weeks from surgery) postoperative emergency room visits [16
      of which resulted in readmission to a hospital over the 9-year study period
      (0.86%): 9 for dysesthetic leg pain, 2 for wound infections, and 5 for poorly
      controlled incisional pain]. Conclusions: Transforaminal endoscopic decompression
      can be successfully carried out in an outpatient surgery center setting.
      Readmissions due to reherniations, postoperative complications, or poor pain
      control are uncommon.

PMID- 30276092
TI  - Heterotopic Ossification After Cervical Total Disc Replacement at 7 Years
      Prevalence, Progression, Clinical Implications, and Risk Factors.
AB  - Background: Heterotopic ossification (HO) is a known risk following cervical
      total disc replacement (CTDR) surgery, but the cause and effect of HO are not
      well understood. Reported HO rates vary, and few studies are specifically
      designed to report HO. The effects on outcomes, and the risk factors for the
      development of HO have been hypothesized and reported in small-population,
      retrospective analyses, using univariate statistics. Methods: Posthoc, multiple
      phase analysis of radiographic, clinical, and demographic data for CTDR as it
      relates to HO was performed. HO was radiographically graded for 164 one-level and
      225 two-level CTDR patients using the McAfee and Mehren system. Analysis was
      performed to correlate HO grades to clinical outcomes and to evaluate potential
      risk factors for the development of HO using demographics and baseline clinical
      measures. Results: At 7 years, 1-level clinically relevant HO grades were 17.6%
      grade 3 and 11.1% grade 4. Two-level clinically relevant HO grades, evaluated
      using the highest patient grade, were 26.6% grade 3 and 10.8% grade 4.
      Interaction between HO and time revealed significance for neck disability index
      (NDI; P = .04) and Visual Analog Scale (VAS) neck pain (P = .02). When analyzed
      at each time point NDI was significant at 48-84 months and VAS neck at 60 months.
      For predictors 2 analyses were run; odds ratios indicated follow-up visit, male
      sex, and preoperative VAS neck pain are related to HO development, whereas hazard
      ratios indicated male sex, obesity, endplate coverage, levels treated, and
      preoperative VAS neck pain. Conclusions: This is the largest study to report HO
      rates, and related outcomes and risk factors. To develop an accurate predictive
      model, further large-scale analyses need to be performed. Based on the results
      reported here, clinically relevant HO should be more accurately described as
      motion-restricting HO until a definitive link to outcomes has been established.

PMID- 30276093
TI  - T1 Slope Minus Cervical Lordosis (TS-CL), the Cervical Answer to PI-LL, Defines
      Cervical Sagittal Deformity in Patients Undergoing Thoracolumbar Osteotomy.
AB  - Background: Cervical kyphosis and C2-C7 plumb line (CPL) are established
      descriptors of cervical sagittal deformity (CSD). Reciprocal changes in these
      parameters have been demonstrated in thoracolumbar deformity correction. The
      purpose of this study was to investigate the development of CSD, using T1 slope
      minus cervical lordosis (TS-CL) to define CSD and to correlate TS-CL and a novel
      global sagittal parameter, cervical-thoracic pelvic angle (CTPA), with CPL.
      Methods: A multicenter, retrospective analysis of patients with thoracolumbar
      deformity undergoing three-column osteotomy was performed. Preoperative and
      postoperative cervical parameters were investigated. Linear regression for
      postoperative values resulted in a CPL of 4 cm corresponding to a TS-CL threshold
      of 17 degrees . Patients were classified based on postoperative TS-CL into
      uncompensated (TS-CL > 17 degrees ) or compensated cohorts (TS-CL < 17 degrees );
      the two were compared using an unpaired t test. Logistic regression modeling was
      used to determine predictors of postoperative CSD. Results: A total of 223
      patients with thoracolumbar deformity (mean age, 57.56 years) were identified.
      CTPA correlated with CPL (preoperative r = .85, postoperative r = .69). TS-CL
      correlated with CTPA (preoperative r = .52, postoperative r = .37) and CPL
      (preoperative r = .52; postoperative r = .37). CSD had greater preoperative CPL
      (P < .001) and CTPA (P < .001). The compensated cohort had a decrease in TS-CL
      (from 10.2 to 8.0) with sagittal vertical axis (SVA) correction, whereas the
      uncompensated had an increase in TS-CL (from 22.3 to 26.8) with all P < .001.
      Reciprocal change was demonstrated in the compensated group given that CL
      decreased with SVA correction (r = .39), but there was no such correlation in the
      uncompensated. Positive predictors of postoperative CSD included baseline TS-CL >
      17 degrees  (P = .007), longer fusion (P = .033), and baseline CTPA (P = .029).
      Conclusions: TS-CL and CTPA correlated significantly with established sagittal
      balance measures. Whereas reciprocal change in cervical and thoracolumbar
      alignment was demonstrated in the compensated cohort, the uncompensated
      population had progression of their cervical deformities after three-column
      osteotomy. Clinical Relevance: The balance between TS-CL mirrors the relationship
      between pelvic incidence minus lumbar lordosis in defining deformities of their
      respective spinal regions.

PMID- 30276094
TI  - Is There an Association With Spino-Pelvic Relationships and Clinical Outcome of
      Type A Thoracic and Lumbar Fractures Treated Non-Surgically?
AB  - Background: The objective was to evaluate if there is an association of the spino
      pelvic relationships and the global spinal alignment with the outcome of AO type
      A injuries treated nonsurgically. Methods: This is a retrospective case series.
      Patients treated nonsurgically for AOSpine type A fractures (T1-L5) with at least
      1 year follow-up identified. A standing antero-posterior and lateral 36-inch
      radiographs and measures of spino-pelvic relationships and sagittal alignment
      were obtained, as well as clinical assessment using the visual analog scale, the
      Short-Form 36 (SF-36) questionnaire, the Oswestry Disability Index (ODI), and
      labor status. Results: Twenty-two patients with 33 fractures were included (L1
      was the most injured level with 18.2%). There were 17 men (77.2%) and the mean
      age was 47.1 years. Follow-up ranged from 12 to 60 months (mean of 27.8 months).
      There were 22 type A1 (66.7%), 3 type A2 (9%), 6 type A3 (18%), and 2 type A4
      (6%) fractures. The ODI ranged from 4% to 58%, with a mean of 24.4%. The SF-36
      physical health score ranged from 23 to 82.25 (mean 49.59), and the mental health
      score ranged from 14.75 to 94.25 (mean 63.28). No association was identified
      between the spino-pelvic measurements, global alignment, and patient-reported
      outcomes. Conclusions: Type A fractures had a clinically relevant amount of long
      term disability even when surgical treatment is not required. Spino-pelvic
      relationships and final global spinal alignment did not associate with outcome
      measurements.

PMID- 30276096
TI  - Treatment of Low Back Pain by Treating the Annular High Intensity Zone (HIZ)
      Lesions Using Percutaneous Transforaminal Endoscopic Disc Surgery.
AB  - Background: The study design was a retrospective case series. The objective was
      to find the clinical success rate of percutaneous transforaminal endoscopic disc
      surgery in patients suffering from discogenic chronic low back pain who were
      showing high intensity zone (HIZ) with degenerated disc as the only abnormality
      in the magnetic resonance imaging (MRI). The HIZ in the posterior annulus in
      degenerated disc is recognized as a pain generator. There are only a few studies
      available in the literature addressing the effect of identification and treatment
      of HIZ in the chronic low back pain patient. Methods: We retrospectively
      evaluated the case records of all the patients who were treated by percutaneous
      endoscopic disc surgery for relief of symptoms as determined by visual analog
      scale (VAS) score, Oswestry Disability Index (ODI), Mac Nab criteria, and the
      consumption of analgesics, who had the predominant symptom of chronic low back
      pain, and whose lumbar spine MRI showed degenerated disc with HIZ and no other
      cause of back pain, like facet joint arthritis or sacroiliac joint arthritis.
      Results: A total of 23 patients were identified to include in the study. Mean
      preoperative duration of low back pain was 13.1 months. Mean follow up after the
      procedure was 29 months. At final follow up, 69.6% of the patients were not
      taking any pain medicines, 17.36% were on frequent analgesic medicines, 13.04%
      were on occasional analgesics. There was statistically significant reduction in
      VAS at 6 weeks postop and final follow up after surgery and the ODI at final
      follow up; 82.6% of patients had an excellent/good outcome as per Mac Nab
      criteria. There were no complications or reoperations in any of the patients.
      Conclusions: Visualization and ablation of the chronic annular pathology in HIZ
      may give an effective and minimally invasive treatment for one of the back pain
      causes.

PMID- 30276095
TI  - Long-Term Clinical Experience with Selectively Constrained SECURE-C Cervical
      Artificial Disc for 1-Level Cervical Disc Disease: Results from Seven-Year Follow
      Up of a Prospective, Randomized, Controlled Investigational Device Exemption
      Clinical Trial.
AB  - Background: This research was initiated to compare the long-term clinical safety
      and effectiveness of the selectively constrained SECURE-C (Globus Medical,
      Audubon, Pennsylvania) Cervical Artificial Disc to anterior cervical discectomy
      and fusion (ACDF). To preserve segmental motion, cervical total disc replacement
      (CTDR) was developed as an alternative to ACDF. Current CTDR designs incorporate
      constrained and unconstrained metal-on-metal or metal-on-polymer articulation
      with various means of fixation. Methods: Eighteen investigational sites
      participated in this prospective clinical trial; 380 patients were enrolled and
      treated in the investigational device exemption study. The first 5 patients
      treated at each site were nonrandomized and received the investigational SECURE-C
      device. Patients were randomized, treated surgically, and evaluated
      postoperatively at 6 weeks, 3 months, 6 months, 12 months, 24 months, and
      annually thereafter through 84 months postoperative. Results: Overall results for
      the randomized cohorts demonstrated statistical superiority of the
      investigational SECURE-C group over the control ACDF group at 84 months
      postoperative. SECURE-C showed clinically significant improvement in pain and
      function in terms of neck disability index and visual analog scale scores, and
      superiority in patient satisfaction was also achieved for patients treated with
      SECURE-C. Conclusion: Clinical study results indicated that the selectively
      constrained SECURE-C Cervical Artificial Disc is as safe and effective as ACDF.
      Long-term results from the Post Approval Study demonstrated that SECURE-C is
      statistically superior to ACDF in terms of overall success and patient
      satisfaction. Lower rates of subsequent index-level surgeries and device-related
      adverse events were observed in the SECURE-C group than in the ACDF group. The
      long-term, level 1 clinical evidence presented here is consistent with other
      reports supporting the safety and efficacy of cervical arthroplasty, and furthers
      advocacy for motion preservation as a viable alternative to fusion.

PMID- 30276098
TI  - Long-Term Experience With Reduction Technique in High-Grade Spondylolisthesis in
      the Young.
AB  - Background: Surgical management of high-grade spondylolisthesis in the young is
      not only challenging but also controversial, from in-situ fusion to complete
      reduction. It is fraught with dangers such as neurological injury,
      pseudoarthrosis, and progressive deformity with subsequent global sagittal
      imbalance. We describe our experience of progressive reduction technique and
      restoration of lumbosacral alignment. Methods: This study is a retrospective
      review of patients who underwent surgery between 1998 and 2012. The surgical
      technique involved positioning the hips in extension with traction, pedicle screw
      fixation, correction of lumbosacral kyphosis with a specific distraction
      maneuver, wide decompression, and gradual reduction of the deformity and
      maintenance of reduction with interbody fusion. All patients were serially
      assessed at 1, 3, and 6 months and yearly thereafter with clinical, radiological,
      and Oswestry Disability Index and Visual Analogue Scale outcome measures.
      Results: Twenty-seven patients with high-grade spondylolisthesis at L5-S1 (3
      cases grade 3, 7 grade 4, 17 grade 5) with an average age of 13.9 years were
      reviewed. Mean follow-up was 120 months (range 24-192). All patients presented a
      solid fusion at the 6-month visit; mean slip percentage was reduced from 89% to
      23%, with all cases reduced to grade 2 or less. The slip angle improved from 45
      degrees  to 3 degrees  postoperatively, with improvement in sacral slope from 13
      degrees  to 35 degrees . Four spondyloptosis patients had concomitant scoliosis
      which corrected spontaneously after the surgery and did not need further
      intervention. All but one patient (96.2%) had good functional outcomes and
      returned to their full normal activities. One patient developed a deep infection
      necessitating implant removal, with eventual deformity progression leading to a
      poor outcome. Three patients (11.1%) suffered partial drop foot that resolved in
      full by 12 weeks. Conclusion: Our technique demonstrated a significant reduction
      of high grade spondylolisthesis, with restoration of global sagittal balance via
      correction of the lumbosacral kyphosis. Though surgically demanding, it is safe
      and reproducible. Level of Evidence: IV.

PMID- 30276097
TI  - Demographic Trends in the Use of Intraoperative Neuromonitoring for Scoliosis
      Surgery in the United States.
AB  - Background: Intraoperative neuromonitoring (ION), such as motor-evoked potential
      (MEP), somatosensory evoked potentials (SSEP), and electromyography (EMG), is
      used to detect impending neurological injuries during spinal surgery. To date,
      little is known about the trends in the use of ION for scoliosis surgery in the
      United States. Methods: A retrospective review was performed using the PearlDiver
      Database to identify patients that had scoliosis surgery with and without ION
      from years 2005 to 2011. Demographic information (such as age, gender, region
      within the United States) and clinical information (such as type of ION and rates
      of neurological injury) were assessed. Results: There were 3618 patients who had
      scoliosis surgery during the study period. Intraoperative neuromonitoring was
      used in 1361 (37.6%) of these cases. The number of cases in which ION was used
      increased from 27% in 2005 to 46.9% in 2011 (P < .0001). Multimodal ION was used
      more commonly than unimodal ION (64.6% versus 35.4%). The most commonly used
      modality was combined SSEP and EMG, while the least used modality was MEP only.
      Neurological injuries occurred in 1.8 and 2.0% of patients that had surgery with
      and without ION, respectively (P = .561). Intraoperative neuromonitoring was used
      most commonly in patients <65 years of age and in the Northeastern part of the
      United States (age P = .006, region P < .0001). Conclusions: The use of ION for
      scoliosis surgery gradually increased annually from 2005 to 2011. Age and
      regional differences were noted with neuromonitoring being most commonly used for
      scoliosis surgery in nonelderly patients and in the Northeastern part of the
      United States. No differences were noted in the risk of neurological injury in
      patients that had surgery with and without ION. Although the findings from this
      study may seem to suggest that ION may not influence the risk of neurologic
      injury, this result must be interpreted with caution as inherently riskier
      surgeries may utilize ION more, leading to an actual reduction in injuries more
      dramatic than observed in this study.

PMID- 30276099
TI  - Transforaminal Endoscopic Decompression of the Lumbar Spine for Stable Isthmic
      Spondylolisthesis as the Least Invasive Surgical Treatment Using the YESS Surgery
      Technique.
AB  - The first author's series has reported and published his 5- to 10-year results in
      a preliminary review of endoscopic transforaminal decompression for degenerative
      and isthmic spondylolisthesis causing sciatica and back pain. This study was
      initiated due to favorable results in relieving both back and leg pain after a
      spine surgeon with isthmic spondylolisthesis who wanted to avoid fusion requested
      consideration for an endoscopic procedure for his own isthmic spondylolisthesis
      condition. After listening to the first author's podium presentation on selective
      endoscopic discectomy and foraminal decompression under local anesthesia in 1995,
      he requested consideration for transforaminal endoscopic decompression for recent
      onset of progressive sciatica from his isthmic spondylolisthesis. He was the
      first patient to undergo endoscopic decompression in our series of 55 patients
      from January 2002 to December 2012 that served as the database for a clinical
      case series review of selective endoscopic discectomy and foraminoplasty in
      patients with degenerative spondylolisthesis who specifically chose to stage the
      author's endoscopic transforaminal decompressive trademarked procedure over
      fusion. The patients were evaluated and considered for the endoscopic procedure
      specifically at their request, even though they were informed about the
      traditional "gold standard" fusion for surgical intervention. At that time the
      medical field did not have the database to study outcomes other than the
      favorable clinical results found in patients who underwent selective endoscopic
      discectomy and foraminoplasty for degenerative spondylolisthesis. These patients
      were accepted for endoscopic spine surgery in a shared clinical decision after
      full disclosure. The patients opted specifically for the Yeung Endoscopic Spine
      Surgery (YESS) technique that included foraminoplasty and dorsal endoscopic
      rhizotomy from the author's evolving clinical experience of 10,000 cases over 27
      years.

PMID- 30276100
TI  - Symptomatic Vertebral Hemangioma of the Posterior Elements Sharing Blood Supply
      with a Radiculomedullary Artery.
AB  - Vertebral hemangiomas are common lesions usually restricted to the vertebral
      body. They are characterized by proliferation of endothelial cells and subsequent
      expansion of vascular spaces within the bone. These lesions are usually
      clinically silent and are discovered incidentally. Only rarely are vertebral
      hemangiomas symptomatic. Here, we present the case of a 68-year-old female with
      an aggressive hemangioma causing neurologic deficit. The lesion was localized
      within the posterior spinal elements, with no involvement of the vertebral body.
      Transarterial embolization was deemed unsafe due to the close proximity of a
      prominent radiculomedullary artery. The patient was treated with posterior
      decompression at T4-T6.

PMID- 30276101
TI  - The 2-Level Experience of Interlaminar Stabilization: 5-Year Follow-Up of a
      Prospective, Randomized Clinical Experience Compared to Fusion for the
      Sustainable Management of Spinal Stenosis.
AB  - Background: To alleviate the symptoms of lumbar spinal stenosis, widely accepted
      methods of surgical treatment include decompression alone and decompression with
      fusion. As an alternative to these methods, interlaminar stabilization (ILS)
      devices with decompression were introduced. There is a large amount of research
      dedicated to examining the efficacy of ILS devices in single-level procedures,
      but fewer studies focus on their efficacy in 2-level procedures. The purpose of
      this study was to compare decompression with instrumented posterolateral fusion
      to decompression with interlaminar stabilization in patients who require surgical
      treatment at 2 levels for lumbar spinal stenosis at 5 years postoperation.
      Methods: Of the 322 patients enrolled in the Investigational Device Exemption
      clinical trial, 116 required surgical treatment at 2 levels. The ILS group
      consisted of 77 patients, and the fusion group consisted of 39 patients. Efficacy
      was measured using composite clinical success (CCS). Patients achieve CCS if they
      achieve all 4 of the following outcomes: >=15-point improvement from baseline
      Oswestry Disability Index (ODI); no reoperation or epidural injections; no
      persistent, new, or increasing neurological deficits; and no major device-related
      complications. Results: There was a 91% rate of follow-up within the participant
      population in the 5-year data. There was a difference trending toward
      significance between groups for the absence of reoperation or epidural injection,
      with 68.8% of ILS patients and only 51.3% of fusion patients meeting this
      criteria (P = .065); 13.0% of ILS patients and 25.7% of fusion patients required
      secondary surgery. The percentage of patients achieving overall CCS was much
      greater in the ILS group than the fusion group, with 55.1% (38/69) of ILS
      patients and only 36.4% (12/33) of fusion patients achieving CCS at month 60 (P =
      .077). With regard to the ODI, the visual analog scale back and worse leg pain,
      the Short Form-12, and the Zurich Claudication Questionnaire, both groups had
      significantly better results at every follow-up time point when compared to their
      respective baseline scores. Conclusions: The 2-level ILS patient group performed
      as well as, if not better than, the 2-level fusion group across almost all
      outcome measures, demonstrating both clinical outcome success and favorably low
      reoperation rates in patients who received ILS surgery. Clinical Relevance: This
      is the first 5-year analysis of the 2-level ILS experience, which supplements
      previous studies that describe the advantages of ILS by extending such advantages
      to 2-level cases.

PMID- 30276102
TI  - Management of Metastatic Spinal Cord Compression in Ireland: Are Surgeons
      Overlooked?
AB  - Background: The National Institute of Health and Clinical Excellence (NICE)
      provide a framework of evidence-based guidelines for the management of metastatic
      spinal cord compression (MSCC). We aimed to compare our center's provision of
      service to these best practice guidelines and discuss key shortcomings with their
      implications for the spinal surgeon. Methods: Patients with radiologic evidence
      of MSCC over a 30-month period were identified using the hospital electronic
      radiological database. A chart review was performed analyzing MSCC management.
      Results: Forty-one patients were identified. Pain was the most common presenting
      complaint, occurring in 76% of patients. Radiotherapy alone was the most common
      therapy employed (93% of patients). A surgical opinion was sought for 51% of
      patients. Histological diagnosis of the causative lesion occurred in 5 patients
      from surgical specimens. Conclusions: Incongruities between NICE guidelines and
      our practice exist. Early involvement of the spinal surgical services needs to be
      encouraged. Establishing a histological diagnosis of the spinal lesion should be
      seen as of therapeutic importance.

PMID- 30276080
TI  - We Need to Talk about Lumbar Total Disc Replacement.
AB  - Background: Replacement of a diseased lumbar intervertebral disc with an
      artificial device, a procedure known as lumbar total disc replacement (LTDR), has
      been practiced since the 1980s. Methods: Comprehensive review of published
      literature germane to LTDR, but comment is restricted to high-quality evidence
      reporting implantation of lumbar artificial discs that have been commercially
      available for at least 15 years at the time of writing and which continue to be
      commercially available. Results: LTDR is shown to be a noninferior (and sometimes
      superior) alternative to lumbar fusion in patients with discogenic low back pain
      and/or radicular pain attributable to lumbar disc degenerative disease (LDDD).
      Further, LTDR is a motion-preserving procedure, and evidence is emerging that it
      may also result in risk reduction for subsequent development and/or progression
      of adjacent segment disease. Conclusions: In spite of the substantial logistical
      challenges to the safe introduction of LTDR to a health care facility, the
      procedure continues to gain acceptance, albeit slowly. Clinical Relevance:
      Patients with LDDD who are considering an offer of spinal surgery can only
      provide valid and informed consent if they have been made aware of all reasonable
      surgical and nonsurgical options that may benefit them. Accordingly, and in those
      cases in which LTDR may have a role to play, patients under consideration for
      other forms of spinal surgery should be informed that this valid procedure
      exists.

PMID- 30276103
TI  - The Efficacy of Liposomal Bupivacaine in Lumbar Spine Surgery.
AB  - Background: Postoperative pain management in spine surgery holds unique
      challenges. The purpose of this study is to determine if the local anesthetic
      liposomal bupivacaine (LB) reduces the total opioid requirement in the first 3
      days following posterior lumbar decompression and fusion (PLDF) surgery for
      degenerative spondylosis. Methods: Fifty patients underwent PLDF surgery in a
      prospective randomized control pilot trial between August 2015 and October 2016
      and were equally allocated to either a treatment (LB) or a control (saline)
      group. Assessments included the 72-hour postoperative opioid requirement
      normalized to 1 morphine milligram equivalent (MME), visual analog scale (VAS),
      and hospital length of stay. Results: LB did not significantly alter the 72-hour
      postoperative opioid requirement compared to saline (11.6 vs. 13.4 MME, P = .40).
      In a subgroup analysis, there was also no significant difference in opioid
      consumption among narcotic-naive patients with either LB or saline. Among
      narcotic tolerant patients, however, opioid consumption was higher with saline
      than LB (20.6 MME vs. 13.3 MME, P = .048). Additionally, pre- and postoperative
      VAS scores and hospital length of stay were not significantly different with
      either LB or saline. Conclusions: In the setting of PLDF surgery, LB injections
      did not significantly reduce the consumption of opioids in the first 3
      postoperative days, nor did the hospital length of stay or VAS pain scores,
      compared to saline. However, LB could be beneficial in reducing the consumption
      of opioids in narcotic-tolerant populations. Level of Evidence: 2.

PMID- 30276104
TI  - Preservation of Spine Motion in the Surgical Treatment of Adolescent Idiopathic
      Scoliosis Using an Innovative Apical Fusion Technique: A 2-Year Follow-Up Pilot
      Study.
AB  - Background: This trial reports the 2-year and immediate postremoval clinical
      outcomes of a novel posterior apical short-segment (PASS) correction technique
      allowing for correction and stabilization of adolescent idiopathic scoliosis
      (AIS) with limited fusion. Methods: Twenty-one consecutive female AIS patients
      were treated at 4 institutions with this novel technique. Arthrodesis was limited
      to the short apical curve after correction with translational and derotational
      forces applied to upper and lower instrumented levels. Instrumentation spanned
      fused and unfused segments with motion and flexibility of unfused segments
      maintained. The long concave rods were removed at maturity. Radiographic data
      collected included preoperative and postoperative data for up to 2 years as well
      as after long rod removal. Results: All 21 patients are beyond 2 years
      postsurgery. Average age at surgery was 14.2 years (11-17 years). A mean of 10.5
      +/- 1 levels per patient were stabilized and 5.0 +/- 0.5 levels (48%) were fused.
      Cobb angle improved from 56.1 degrees  +/- 8.0 degrees  to 20.8 degrees  +/- 7.8
      degrees  (62.2% improvement) at 1 year and 20.9 degrees  +/- 8.4 degrees , (62.0%
      improvement) at 2 years postsurgery. In levels instrumented but not fused, motion
      was 26 degrees  +/- 6 degrees  preoperatively compared to 10 degrees  +/- 4
      degrees  at 1 year postsurgery, demonstrating 38% maintenance of mobility in
      nonfused segments. There was no report of implant-related complications.
      Conclusions: PASS correction technique corrected the deformity profile in AIS
      patients with a lower implant density while sparing 52% of the instrumented
      levels from fusion through the 2-year follow-up.

PMID- 30276105
TI  - Trends in the Use of Bone Morphogenetic Protein-2 in Adult Spinal Deformity
      Surgery: A 10-Year Analysis of 54 054 Patients.
AB  - Background: Bone morphogenetic protein-2 (BMP-2) is an available bone graft
      option in spinal fusion surgery. The purpose of this study is to investigate the
      trends of BMP-2 utilization in adult spinal deformity (ASD) surgery. Methods: The
      Nationwide Inpatient Sample database from 2002 to 2011 was reviewed. Inclusion
      criteria were patients over 18 years of age who underwent spinal fusion for ASD.
      Trends of BMP-2 use were examined over time, as well as stratified based on
      patient and surgical characteristics. All analyses were done after application of
      discharge weights to produce national estimates. Results: There were 54 054
      patients who met inclusion criteria and were included in this study. The overall
      rate of BMP-2 use was 39.7% (95% confidence interval 35.0%- 44.3%). Overall,
      there was steady increase in its use over time, with the highest peak in 2009
      (55.3% of all cases used BMP-2), and then a decrease up to 37.9% in 2011 (P <
      .001). The rate of BMP-2 use was significantly higher for patients older than 54
      years of age (compared to patients <54, P < .001). It was also higher in females
      (P = .009), Caucasian patients (P = .006), and Medicare patients (P = .006). Its
      use was 28.6% in the Northeast, 38.1% in the South, 45.2% in the Midwest, and
      48.2% in the West (P = .035). Circumferential procedures had the highest rate of
      BMP-2 use (44.3%, P = .045). Average total hospital charges were $152,403 +/-
      117,454 for patients who did not receive BMP-2 and $205,426 +/- 137,561 for
      patients who did (P < .001). Conclusion: After analysis of a large nationwide
      database, it was found that the rate of BMP-2 use in ASD surgery is approximately
      40%. There was a significant increase in use from 2002 to 2009, and a decrease
      thereafter. The highest rates of use were found in older patients, female
      patients, white patients, Medicare patients, circumferential approaches, and
      patients undergoing surgery in the Midwest and West regions.

PMID- 30276106
TI  - Chromium and Nickel Concentrations in Subjects with a Stainless Steel Metal-on
      Metal Cervical Disc Arthroplasty: Results from a Prospective Longitudinal Study
      with 7 Years Follow-Up.
AB  - Background: Cervical disc arthroplasty (CDA) has emerged as an alternative to
      anterior cervical discectomy and fusion for degenerative cervical disc disease.
      The artificial discs provide intervertebral motion using multicomponent
      articulation and thus tend to generate particulate debris and soluble metal ions.
      Limited information is available on the long-term metal concentrations and
      associated systemic adverse events observed in metal-on-metal CDA. Serum chromium
      (Cr) and nickel (Ni) concentrations were assessed in patients implanted with ball
      in-trough stainless steel-based cervical disc through 7 years. Methods: A
      prospective, nonrandomized longitudinal study was conducted that included 25
      patients following rigorous exclusion criteria that included no previous
      permanent metal implants and no professional exposure to metal particles. Blood
      serum Cr and Ni concentrations were assayed preoperatively and at 3, 6, 12, 24,
      36, 60, and 84 months postoperatively using high-resolution inductively coupled
      plasma-mass spectrometry. Longitudinal statistical comparisons were made using
      the Friedman test with statistical significance at P < .05. Results: Median serum
      concentrations determined preoperatively and at 3, 6, 12, 24, 36, 60, and 84
      months postoperatively were 0.074, 0.106, 0.132, 0.170, 0.172, 0.274, 0.192, and
      0.203 ng/mL for Cr and 0.085, 0.178, 0.222, 0.175, 0.205, 0.284, 0.181, and 0.194
      ng/mL for Ni. The serum Cr concentrations were statistically higher for all
      postoperative time periods compared to preoperative concentration (Friedman P
      <.01), whereas serum Ni concentration was statistically higher at the 84-month
      postoperative time period than the preoperative concentration (Friedman P <.01)
      and then the concentration at 3, 12, 24, and 60 months postoperatively (Friedman
      P < .03). Conclusions: The Cr concentrations detected at all postoperative times
      were statistically higher than preoperative concentrations, whereas Ni
      concentration was statistically higher than the preoperative concentration only
      at 84 months.

PMID- 30276107
TI  - Comparison of Stand-Alone, Transpsoas Lateral Interbody Fusion at L3-4 and
      Cranial vs Transforaminal Interbody Fusion at L3-4 and L4-5 for the Treatment of
      Lumbar Adjacent Segment Disease.
AB  - Study Design: Retrospective cohort study. Objective: To compare outcomes and
      complications of stand-alone minimally invasive lateral interbody fusion (LIF) vs
      revision posterior surgery for the treatment of lumbar adjacent segment disease.
      Methods: Adults who underwent LIF or transforaminal lumbar interbody fusion
      (TLIF) for adjacent segment disease were compared. Exclusion criteria: >grade 1
      spondylolisthesis, posterior approach after LIF, and L5/S1 surgery. Patient
      demographics, estimated blood loss, hospital length of stay, complications,
      reoperations, health-related quality of life measures, and radiographs were
      examined. Data were analyzed with the chi2, Wilcoxon signed rank, and Mann
      Whitney U tests. Results: A total of 17 LIF and 16 TLIF patients were included.
      Demographics were similar. Follow up was similar (LIF: 22.9 +/- 11.8 months vs
      TLIF: 22.0 +/- 4.6 months; P = .86). The LIF patients had significantly less
      blood loss (LIF: 36 +/- 16 mL vs TLIF: 700 +/- 767 mL; P < .001) and shorter
      length of stay (LIF: 2.6 +/- 2.9 days vs TLIF: 3.3 +/- 0.9 days; P = .001). There
      were no intraoperative complications. Revision rate was 4 of 17 in LIF and 3 of
      16 in TLIF (P = .73). Baseline health-related quality of life and radiographic
      measurements were similar. In both groups, back and leg pain scores significantly
      improved, and in LIF, the Owestry Disability Index, and EuroQol-5D significantly
      improved. The LIF had a significant increase in intervertebral height (LIF: 4.8
      +/- 2.9 mm, P < .001, TLIF: 1.3 +/- 3.4 mm, P = .37), which was significantly
      greater for LIF than TLIF (P = .002). Similarly, LIF had a significant increase
      in segmental lordosis (LIF: 5.6 degrees  +/- 4.9 degrees , P < .001, TLIF: 3.6
      degrees  +/- 8.6 degrees , P = .16), which was not significantly different
      between groups. Conclusions: Patients with adjacent segment disease may receive
      significant benefit from stand-alone LIF or TLIF. The LIF offers advantages of
      less blood loss and a shorter hospital stay. Level of Evidence: 3.

PMID- 30276108
TI  - Comparison of Quality of Life Between Men and Women Who Underwent Transforaminal
      Percutaneous Endoscopic Discectomy for Lumbar Disc Herniation.
AB  - Background: Studies describing the efficacy of transforaminal percutaneous
      endoscopic discectomy (TPED) on shortness of recovery and improvement of
      postoperative quality of life are limited, especially regarding gender, something
      that has never been reported before in the literature. The purpose of this study
      is to evaluate, in accordance with the sex of the patients, possible differences
      in the health-related quality of life of those who underwent TPED for lumbar disc
      herniation (LDH). Methods: A total of 76 patients diagnosed and treated with TPED
      for LDH with 1-year follow-up were selected and divided into 2 groups of equal
      number depending on sex. Their quality of life was evaluated by using the 36-Item
      Short Form Health Survey before the operation, then 6 weeks and 3, 6, and 12
      months postoperatively. A statistical analysis was conducted, in order to compare
      the 8 scaled scores of the 36-Item Short Form Health Survey, each time combining
      2 chronological phases for the total number of patients, for each group, and
      between groups. Results: Fifty-two (68.4%) patients were <=63 years old, whereas
      the other 24 (31.4%) were >63 years old (mean +/-  SD = 56.5 +/-  12.1 years).
      Apart from the physical function domain, the scores were higher in every visit
      for the 2 groups, but the change between groups was not significant. Women had a
      significantly higher increase of physical function score in 3 months after TPED
      and in the interval 6 weeks to 3 months compared with men. However, in the
      intervals 3 to 6 months and 3 to 12 months, men presented a significantly higher
      increase compared with women. Conclusions: Statistically significant improvement
      of the quality of life for both men and women was observed. Generally, there was
      no significant difference between the 2 groups. With regard to the physical
      functioning, it appears to be a significant difference that is counterpoised over
      time. Level of evidence: 2. Clinical relevance: Transforaminal percutaneous
      endoscopic discectomy for LDH does not present major differences in the
      improvement of quality of life regarding gender.

PMID- 30276109
TI  - Preclinical Comparison of Thermal Tissue Effects from Traditional Electrosurgery
      and a Low-Temperature Electrosurgical Device during Anterior Cervical Discectomy
      and Fusion.
AB  - Background: Exposure of the anterior cervical spine requires dissection in
      proximity to critical neurovascular structures. Monopolar electrosurgical (ES)
      devices generate heat in contacted tissues, resulting in thermal damage and
      temperature change. This study examined depth of thermal injury and temperature
      change associated with use of a low-temperature electrosurgical device (LTD)
      compared to traditional electrosurgery during a cadaveric anterior cervical
      discectomy and fusion (ACDF) dissection. Methods: ACDF was performed, using ES or
      LTD, on cervical spines (C3-4 and C4-5) from 2 fresh human cadavers with intact
      neck soft tissues and no history of surgery. Cadavers were maintained at 22-23
      degrees C, and fiber-optic temperature sensors (Neoptix, Quebec City, Quebec,
      Canada) were placed near relevant structures to measure changes during
      dissection. Depth of thermal injury was assessed by hematoxylin and eosin and
      Masson's trichrome histology of fixed tissue specimens. Results: Use of the LTD
      resulted in a statistically significant reduction in temperature change at
      platysma (3.0 +/- 1.04 vs. 11.41 +/- 3.10 degrees C, P = .003), carotid sheath
      (7.32 +/- 1.13 vs. 15.57 +/- 2.56 degrees C, P = .007), and longus colli (6.11 +/
      1.32 vs. 12.9 +/- 3.62 degrees C, P = .016) compared to ES. Temperature change
      at the trachea was similar between groups (6.06 +/- 1.99 vs. 4.96 +/- 1.89
      degrees C, P = .528). Histology showed that LTD produced less mean and maximal
      depth of thermal injury compared to ES (mean: 0.5 vs. 1.2 mm; max: 0.9 vs. 1.8
      mm; P < .05). Conclusions: The results of this pilot study demonstrate that
      anterior cervical spine exposure using an LTD reduces tissue temperature change
      and depth of thermal injury compared to ES. Clinical Relevance: Although
      exploratory, these results suggest that use of an LTD during ACDF may reduce the
      extent of thermal tissue injury during dissection. Future studies in live animal
      models are warranted to determine if thermal injury is a potential cause of
      common exposure-related complications, such as dysphagia and dysphonia.

PMID- 30276110
TI  - An Analysis of Implant Retention and Antibiotic Suppression in Instrumented Spine
      Infections: A Preliminary Data Set of 67 Patients.
AB  - Background: It is unclear whether patients can be taken off suppressive
      antibiotics with infected retained instrumentation. This study aimed to
      retrospectively analyze the perioperative course and antibiotic regimen that led
      to the clinical intervention of patients with infected spinal instrumentation.
      Methods: Consecutive adult patients with spine instrumentation who suffered
      surgical site infections (SSI) requiring debridement were retrospectively
      analyzed. The patients were grouped into 4 cohorts based on their clinical
      intervention: removal of instrumentation, reinstrumentation, retention of
      instrumentation with continued antibiotic suppression, and retention of
      instrumentation with no antibiotic suppression. Patient factors, infection
      factors, debridement, and antibiosis were compared. Results: Of the 67 patients
      with SSI after spine surgery and instrumentation, 19 (28%) had their
      instrumentation removed, 6 (9%) had their instrumentation exchanged, 25 (37%) had
      their instrumentation retained and were on antibiotic suppression, and 17 (25%)
      had their instrumentation retained without any suppression. Those who had their
      instrumentation removed had a later presentation of their infection averaging 85
      days (range 6-280 days) postoperatively. There was an earlier presentation for
      those who retained their implants, with suppression averaging 19 days (range 9
      39) and no suppression averaging 29 days (range 6-90 days) post operatively (P <
      .001). Conclusions: None of the patients with retained instrumentation without
      suppression had recurrence of infections after long-term follow-up. Lifelong
      antibiotic suppression may not be required with SSI that present early after
      early aggressive debridement. Patients with infections detected later are
      difficult to treat without removal of their original instrumentation. Clinical
      Relevance: This study presents the outcomes of surgical and antibiotic factors in
      patients with infected spinal instrumentation.

PMID- 30276112
TI  - Enhancing Evaluation of Cervical Spine: Thresholds for Normal CT Relationships in
      the Subaxial Cervical Spine.
AB  - Background: Very little normative computed tomography (CT) scan data exist
      defining expected relationships of vertebral structures in the intact cervical
      spine. Better understanding of normal relationships should improve sensitivity of
      injury detection, particularly for facet subluxation. The purpose of this paper
      was to describe the normal anatomical relationships and most sensitive
      measurements to detect abnormal alignment in the subaxial cervical spine.
      Methods: A group of 30 CT scans with no documented cervical spine injury were
      utilized from an established database in a trauma population. Twenty-two
      anatomical measurements were made for each level of the subaxial cervical spine
      using Microview software. For the purposes of measurement, the upper confidence
      limit of normal was reported as two standard deviations from the mean. Results:
      The novel, CT based measurements of bone articulation were generally smaller and
      had lower confidence intervals compared to traditional radiographic measurements
      of midline structures (such as interspinous distance, interlaminar widening, disc
      space widening). The upper limit of normal of facet joint height was reported
      (1.54 mm anterior, 1.27 mm posterior, and 2.0 mm midportion), which may help
      identify distractive-flexion injuries. The upper limit of normal vertebral
      translation (2.0 mm) was also reported to identify translation/rotation injuries.
      Conclusions: Normal CT measurements for the subaxial cervical spine, especially
      in the facets, were found to have small confidence limits and variation. Based
      upon these findings, we conclude that facet measurements and translation may be
      better screening tools than traditional radiographic criteria based upon midline
      structures. Using these measurements may improve detection of cervical spine
      injuries warranting further imaging or investigation and reducing missed
      injuries. Clinical Relevance: Improved understanding of normal anatomic measures
      in the subaxial spine will allow for better screening and identification of
      injuries.

PMID- 30276111
TI  - Suitability of Administrative Databases for Durotomy Incidence Assessment:
      Comparison to the Incidence Associated With Bone-Removal Devices, Calculated
      Using a Systemic Literature Review and Clinical Data.
AB  - Background: Durotomy is a major complication of spinal surgery, potentially
      leading to additional clinical complications, longer hospitalization, and
      increased costs. A reference durotomy incidence rate is useful for the evaluation
      of the safety of different surgical aspects. However, the literature offers a
      wide range of incidence rates, complicating this comparison. Theoretically, a
      reference incidence value can be extracted from administrative databases,
      containing a large number of procedures. However, it is suspected that these
      databases suffer from underreporting of complications. This study aims to
      evaluate durotomy incidence using several large-scale databases and to assess the
      ability to use it as a reference by comparison to durotomy incidences directly
      associated with 4 bone removal devices, including the commonly used high-speed
      drill. Methods: Durotomy overall incidence was estimated from several
      administrative databases using different methods in order to achieve minimal and
      maximal estimations. Durotomy incidences for 3 bone removal devices were derived
      using literature meta-analysis, and the incidence for the fourth device was
      calculated using clinical data. Results: The incidence range of durotomy
      according to the databases was 2.8-3.5%. The calculated incidence of durotomy for
      the studied devices was 0.4-2.91%. The highest rate, 2.91%, is associated with
      the commonly used high-speed drill combined with Kerrison Rongeur and bone
      punches. Since bone-removal devices are just one of the possible causes of dural
      tears, the general incidence is expected to be higher than the incidence
      associated with the devices, yet even the maximal estimation, 3.5%, was only
      slightly higher, suggesting that the speculation of underreporting of dural tears
      to these databases is probably true, as also supported by the mostly higher
      incidences reported in the literature. Conclusions: Hospital administrative
      databases seem to show a lower-than-reasonable incidence of durotomy, suggesting
      possible underreporting. Researchers should therefore use this tool with caution.
      Reduction of the absolute durotomy incidence by approximately 2.5% can be
      achieved by improving the safety of bone-removal devices.

PMID- 30276113
TI  - Biomechanics of an Expandable Lumbar Interbody Fusion Cage Deployed Through
      Transforaminal Approach.
AB  - Background: A novel expandable lumbar interbody fusion cage has been developed
      which allows for a broad endplate footprint similar to an anterior lumbar
      interbody fusion; however, it is deployed from a minimally invasive
      transforaminal unilateral approach. The perceived benefit is a stable
      circumferential fusion from a single approach that maintains the anterior tension
      band of the anterior longitudinal ligament. The purpose of this biomechanics
      laboratory study was to evaluate the biomechanical stability of an expandable
      lumbar interbody cage inserted using a transforaminal approach and deployed in
      situ compared to a traditional lumbar interbody cage inserted using an anterior
      approach (control device). Methods: Twelve cadaveric spine specimens (L1-5) were
      tested intact and after implantation of both the control and experimental devices
      in 2 (L2-3 and L3-4) segments of each specimen; the assignments of the control
      and experimental devices to these segments were alternated. Effect of
      supplemental pedicle screw-rod stabilization was also assessed. Moments were
      applied to the specimens in flexionextension (FE), lateral bending (LB), and
      axial rotation (AR). The effect of physiologic preload on construct stability was
      evaluated in FE. Segmental motions were measured using an optoelectronic motion
      measurement system. Results: The deployable expendable transforaminal lumbar
      interbody fusion (TLIF) cage and control devices significantly reduced FE motion
      with and without compressive preload when compared to the intact condition (P <
      .05). Segmental motions in LB and AR were also significantly reduced with both
      devices (P < .05). Under no preload, the deployable expendable TLIF cage
      construct resulted in significantly smaller FE motion compared to the control
      cage construct (P < .01). Under all other testing modes (FE under 400N preload,
      LB, and AR), the postoperative motions of the 2 constructs did not differ
      statistically (P > .05). Adding bilateral pedicle screws resulted in further
      reduction of range of motion for all loading modes compared to intact condition,
      with no statistical difference between the 2 constructs (P > .05). Conclusions:
      The ability of the deployable expendable interbody cage in reducing segmental
      motions was equivalent to the control cage when used as a standalone construct
      and also when supplemented with bilateral pedicle screw-rod instrumentation. The
      larger footprint of the fully deployed TLIF cage combined with preservation of
      the anterior soft-tissue tension band may provide a better biomechanical fusion
      environment by combining the advantages of the traditional anterior lumbar
      interbody fusion and TLIF approaches.

PMID- 30276114
TI  - Comparison of Surgical Outcome Between Diabetic Versus Nondiabetic Patients After
      Lumbar Fusion.
AB  - Background: The prevalence of diabetes mellitus (DM) is increasing worldwide.
      Thereby, an increasing rate of patients with DM are subjecting to spine surgery.
      Reviewing the literature, a higher rate of surgery-related complications is
      reported in DM patients. There is no prospective study comparing the outcomes of
      lumbar fusion surgery in patients with and without DM. We aimed to investigate
      whether DM is associated with worse patient-reported outcomes, lower fusion rate,
      and higher complication rate in subjects undergoing spinal lumbar fusion surgery.
      Methods: Forty-eight subjects with DM (DM group) and 48 controls (control group)
      were recruited. Data regarding age, duration of diabetes, comorbidities, fasting
      blood sugar, HbA1c, insulin dependence, duration of operation and the volume of
      bleeding, and the number of infused packed cell were recorded for all patients.
      Pain and functional status of the patients using the visual analogue scale (VAS)
      and Oswestry Disability Index (ODI) were measured before operation and 2 weeks, 6
      months, and 1 year after lumbar spinal fusion surgery. Using lumbar computed
      tomography scan and anteroposterior and lateral x-ray 1 year after the surgery,
      fusion was assessed. Results: Fusion rate after 1 year was 78% in the control
      group and 53% in the DM group (P = .02). Patients with DM had higher VAS scores
      comparing to controls 1 year after the operation, but the difference was not
      significant (P = .07). However, comparing the functional status of the subjects,
      significantly higher ODI scores were found among DM patients comparing to
      controls (P = .002). Conclusion: Rate of fusion among diabetic patients who
      undergo lumbar spinal fusion surgery is lower than healthy controls. Spine
      surgeons should consider this to provide the best possible facilities during the
      surgery to increase the fusion rate in these patients.

PMID- 30276115
TI  - Hyperbaric Oxygen Therapy Side Effects - Where Do We Stand?

PMID- 30276116
TI  - The Adjunctive Use of Biologically Engineered Products in Plastic Surgery
      Practice.
AB  - Biologically engineered products are medical devices offer support and structure
      for wound healing by providing a scaffold for cell growth and proliferation. In
      the field of plastic surgery, these devices are being used to improve the
      outcomes of surgical closure in selected patients. The purpose of this article is
      to provide an overview of the source, indications, mechanisms, and outcomes of
      commonly used biologic products in wound healing. It will also provide an
      understanding of how biologics can be of value to patients with significant
      tissue defects requiring plastic surgery.

PMID- 30276117
TI  - The Role of an Esterified Hyaluronic Acid Matrix in Wound Healing, a Case Series.

PMID- 30276118
TI  - Impact of Renal Failure on Wounds Healing.

PMID- 30276119
TI  - Summary Article on Advanced Ulcer Treatments used in the Operating Room.

PMID- 30276120
TI  - Quantitative Monitoring Wound Healing Status Through Three-dimensional Imaging on
      Mobile Platforms.
AB  - There are approximately 6.5 million patients in the U.S. suffering from chronic
      wounds and approximately 140,000 patients hospitalized every year with new
      wounds. With a long healing process, this demands the need for a non-contact, low
      cost, and remote monitoring solution that can assist clinicians in diagnosing and
      treating a patient's wound. This will reduce the burden of countless office
      visits, especially for those who are elderly and incapacitated. We present a
      mobile platform based wound 3D imaging app. The app is the only integrated
      measurement solution encompassing wound area and volume through low cost yet
      accurate 3D imaging. Extensive experiments show the app has 1.14% and 4.41%
      relative errors for wound area and volume measurement respectively, far exceeding
      currently employed clinic methods. In addition, non-invasive volume measurement
      methods currently use expensive industrial 3D (>$20K) cameras, but our solution
      provides cheap and accurate results.

PMID- 30276121
TI  - Limb-Threatening Arterial Thrombosis in a Patient with Eosinophilic
      Granulomatosis with Polyangiitis.
AB  - Eosinophilic granulomatosis (EGPA), or Churg-Strauss syndrome, is a rare and
      necrotizing systemic vasculitis, which affects small-to-medium-sized vessels and
      often manifests with severe asthma and eosinophilia. We report a case of a 72
      year-old male with a two-year lung-biopsy proven history of EGPA who presented
      with retiform purpura and patchy necrosis on his bilateral shins, which
      progressed to sharply demarcated, stellate ulcerations with surrounding erythema
      within two weeks. Laboratory work up revealed elevated anti-Cardiolipin IgM,
      rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein,
      although P-neutrophil cytoplasmic antibody (P-ANCA) and C-neutrophil cytoplasmic
      antibody (C-ANCA) were negative. Vascular studies revealed long anterior tibial
      and dorsalis pedis artery occlusion and severe small vessel disease in plantar
      digital arteries. Despite treatment with intravenous cyclophosphamide, pulse-dose
      methylprednisolone, and pentoxifylline, the patient experienced disease
      progression and limb threatening arterial thrombosis. This case highlights the
      importance of vascular and neuropathic sequelae that may result from untreated or
      undertreated EGPA in P-ANCA-negative patients without active pulmonary symptoms.

PMID- 30276122
TI  - Placental Membranes for Management of Refractory Cutaneous Sinus Tracts of
      Surgical Origin: A Pilot Study.
AB  - Despite advances in surgical technique, postoperative complications may lead to
      refractory cutaneous sinus tracts or tunnels. Negative pressure wound therapy is
      difficult to apply in longer tracts with a narrow diameter opening and
      conservative treatment failures ultimately necessitate surgical revisions. The
      aim of this pilot study was a clinical utility assessment of two different
      commercial placental membrane products for refractory cutaneous sinus tracts of
      surgical origin. Patients were treated with viable cryopreserved placental
      membrane (vCPM, n = 6) or devitalized dehydrated amnion/chorion membrane (dHACM,
      n = 6). The primary outcome measurement was the proportion of complete sinus
      tract depth resolution without exudate. Secondary endpoints included 4-week
      percent reduction in sinus tract probing depth and peri-tract wound surface area,
      days and number of grafts to resolution, number of wound-related infections, and
      1-year recurrence rate for closed sinus tracts. All vCPM patients demonstrated
      complete sinus tract resolution compared to zero closures in the dHACM group (p =
      0.00216). The vCPM group achieved greater percent reduction in probing depth
      (73.3 +/- 21.9 versus -4.4 +/- 91.3) and surrounding wound surface area (34.8 +/-
      86.8 versus -279.3 +/- 454.9) at 4 weeks than dHACM. The use of viable intact
      cryopreserved placental membrane has demonstrated positive clinical outcomes for
      the treatment for refractory exudative sinus tracts and may be an alternative to
      repeat surgical intervention.

PMID- 30276123
TI  - Management of a Recurrent Pyogenic Granuloma of the Inferior Lip with Pulsed Dye
      Laser: A Case Report.
AB  - Pyogenic granuloma (PG) is a common, acquired, benign vascular reactive
      proliferation. This article presents the unique and successful pulsed dye laser
      treatment of a labial PG on a 60-year-old patient.

PMID- 30276124
TI  - Wound Management of Systemic Sclerosis using Maggots: Out-of-Sight Out-of-Mind.

PMID- 30276125
TI  - The Death of the Kennedy Terminal Ulcer.
AB  - The concept of the Kennedy Terminal Ulcer (KTU) has been ubiquitous in attempting
      to explain the development of pressure based tissue injuries in patients with
      actual or presumed terminal conditions. The concept is problematic in that it
      uses factors other than pressure to explain the development and progression of
      pressure based tissue injuries, specifically the presence of a terminal
      condition. Based on the most current understanding of how pressure based tissue
      injuries develop and progress, the concept of The Kennedy Terminal Ulcer appears
      to be without physiologic basis and based solely on observation. Since systemic
      factors affect all tissues with relative equality, the development of a single
      locus of injury must logically be based on a single locus of cause and affect.
      The presumption that a single locus of injury will develop in an arbitrary
      location based on a systemic set of factors is untenable. A new concept called
      Miller Pressure Equivalent Injuries is proposed to refute the concept of a single
      pressure based tissue injury developing based solely on terminal systemic factors
      and why these previously presumed terminal condition associated pressure based
      injuries occur.

PMID- 30276126
TI  - Malleolar Ulceration Induced by Hydroxyurea Therapy for Chronic Eosinophila.
AB  - A 59-year-old African American female presented to a plastic surgery office in
      consultation for a very painful non-healing wound of her right lateral malleolus.
      An incisional biopsy was performed and ultimately a diagnosis of hydroxyurea
      induced ulcer was concluded. Descriptions of this entity are rare in the surgical
      and wound care professional literature. This diagnosis does appear in the
      hematology/oncology literature; however, these practitioners may not be the first
      to examine a patient with the development of such an ulcer. This article presents
      the pathophysiology and clinical presentation of hydroxyurea-induced ulceration
      as well as the characteristics of hydroxyurea-induced ulceration in addition to
      the case study.

PMID- 30276127
TI  - Maggot Infestation: Various Treatment Modalities.
AB  - The invasion of the skin and subcutaneous tissue by the larvae (Maggot) is known
      as Maggot infestation. It was found that farmers who are working in agricultural
      fields are more prone to this infestation. A case of 60 year old male patient
      with ulceration on leg for 10 days which was initially smaller and later
      developed into a larger wound, due to maggot larvae. This case report illustrates
      the importance and method of treating this cutaneous myiasis.

PMID- 30276128
TI  - The Kennedy Terminal Ulcer - Alive and Well.

PMID- 30276129
TI  - A giant hemorrhagic adrenal pseudocyst mimicking hydatid cyst.

PMID- 30276130
TI  - A case of IgG4-related renal pseudotumor in a child with history of Wilms tumor.

PMID- 30276131
TI  - A Review about Regulatory Status and Recent Patents of Pharmaceutical Co
      Crystals.
AB  - Pharmaceutical Co-crystals are not new, they have gained much attention since the
      last decade among scientists and pharmaceutical industry. Pharmaceutical co
      crystals are multicomponent systems composed of two or more molecules and held
      together by non-covalent interactions. The development of pharmaceutical co
      crystals, a new solid crystalline form, offer superior physico-chemical
      properties (such as melting point, stability, solubility, permeability,
      bioavailability, taste masking, etc.) without altering the pharmacological
      properties. Recently, with the upsurge in the growth of Pharmaceutical co
      crystals, the major concern is over the regulatory status of co-crystals. With
      the new guidelines from United States Food and Drug Administration (USFDA) and
      European Medicines Agency (EMA), the status has become even more complicated due
      to significantly different opinions. This review highlights whether co-crystals
      fulfil the requirements for the grant of a patent or not and how cocrystals are
      going to affect the present scenario of pharmaceuticals.

PMID- 30276133
TI  - Isotretinoin; A review on the Utilization Pattern in Pregnancy.
AB  - Purpose: Isotretinoin is the most effective anti-acne drug with a long-term
      remission. However; it contains severe teratogenic effects with serious adverse
      drug reactions, which limits the use of medication. Methods: To review the use of
      isotretinoin during pregnancy, we carried out a comprehensive search of
      literature in Google Scholar, Scopus and PubMed/Medline from their inception
      until April 2015. Results: Database searching identified 277 records, of which,
      38 articles were retrieved according to abstract and title assessment. After full
      text review, 17 articles were excluded and finally, a total of 21 studies met the
      inclusion criteria. Data showed an increased pattern in the use of isotretinoin.
      In some studies, health care providers were not fully adhered to the risk
      reduction programs in pregnancy. Exposing to isotretinoin among pregnant women
      has still occurred due to detrimental adherence to risk reduction programs which
      resulted in live-born infants with different kinds of abnormalities. Conclusion:
      Despite the known serious adverse effect of isotretinoin, the use of drug was not
      based on the guidelines in some cases, which needs more attentions to prevent the
      severe drug related problems.

PMID- 30276132
TI  - Natural Phytotherapeutic Antioxidants in the Treatment of Mercury Intoxication-A
      Review.
AB  - Heavy metals taken into the organism can make the toxic effects on the metabolism
      in various ways. For example, they may interact with proteins to alter and
      inhibit their enzymatic and structural functions. Mercury is one of the toxic
      elements that are widely distributed in nature. Mercury toxicity poses a serious
      threat to human health. It is an element that causes oxidative stress to increase
      in individuals, leading to tissue damage. Oxidative stress is the result of the
      imbalance between the production of oxidative species and cellular antioxidant
      defense. Phytotherapy continues to play an important role in health care. Natural
      phytotherapeutic antioxidants, exhibit a broad sequence of biological impacts,
      including anti-oxidative stress, anti-aging, anti-toxicicity and anticancer. Many
      studies have also shown that the phytotherapeutic agents play an important role
      in the removal of mercury from the tissue and in reducing oxidative stress. Our
      goal in this review was to investigate alternative ways of extracting the mercury
      in the tissue.

PMID- 30276135
TI  - Nanotechnology in Wound Healing; Semisolid Dosage Forms Containing Curcumin
      Ampicillin Solid Lipid Nanoparticles, in-Vitro, Ex-Vivo and in-Vivo
      Characteristics.
AB  - Purpose: Wound healing is a natural biologic process, but the duration of it may
      take too long. Trying to shorten this process is one of the challenges for
      scientists. Many technologies were applied to achieve this goal as well as
      nanotechnology. In this study semi solid formulations containing curcumin and
      ampicillin solid lipid nanoparticles (SLNs) were prepared to evaluate as burn
      wound healing agent. Methods: Curcumin as an anti-inflammatory and anti-bacterial
      agent and ampicillin as an antibiotic were applied. In-vitro and in-vivo
      evaluations were carried out. Particle size, loading efficiency, release profile,
      morphology and anti-bacterial efficacy of desired nanoparticles were evaluated at
      first. Then the remaining of the antibacterial effect in semi solid preparations
      was studied. Animal studies for both toxicology using rabbits and skin burn model
      using rats were designed. Pathology studies after applying of formulations was
      done too. Results: Desired nanoparticles were spherical in shape and particle
      size in range of 112-121 nm, with low zeta potential. For increasing stability of
      particles they were freeze dried using cryoprotectant. Lyophilized particles show
      no significant size enlargement. Results showed that both ointment and gel
      preparations have reasonable anti-bacterial effects, both of them cause
      increasing in the rate of wound healing in comparison with placebos and control
      groups and none of the formulations showed acute toxicity. Conclusion: It seems
      that using nanotechnology could shorten wound healing process to reduce treatment
      costs and increase compliance of patients.

PMID- 30276134
TI  - Targeted Co-Delivery of Docetaxel and cMET siRNA for Treatment of Mucin1
      Overexpressing Breast Cancer Cells.
AB  - Purpose: Targeted treatment of breast cancer through combination of
      chemotherapeutic agents and siRNA had been drawing much attention in recent
      researches. This study was carried out to evaluate mucin1 aptamer-conjugated
      chitosan nanoparticles containing docetaxel and cMET siRNA on SKBR3 cells.
      Methods: Nano-drugs were characterized by transmission electron microscope,
      Zetasizer and loading efficiency calculation. siRNA entrapment onto
      nanoparticles, stability of siRNA-loaded nanoparticles and conjugation of mucin1
      aptamer to nanoparticles were evaluated via separate electrophoresis. Cellular
      uptake of the targeted nanoparticles was evaluated through GFP-plasmid expression
      in mucin1+ SKBR3 vs. mucin1- CHO cells. Protein expression, cell viability and
      gene expression were assessed by Western Blotting, MTT assay, and Quantitative
      Real Time-PCR, respectively. Results: Characterization of nano-drugs represented
      the ideal size (110.5+/- 3.9 nm), zeta potential (11.6+/- 0.8 mV), and loading
      efficiency of 90.7% and 88.3% for siRNA and docetaxel, respectively. Different
      gel electrophoresis affirmed the conjugation of aptamers to nanoparticles and
      entrapment of siRNA onto nanoparticles. Increased cellular uptake of aptamer
      conjugated nanoparticles was confirmed by GFP expression. cMET gene silencing was
      confirmed by Western Blotting. The significant (p <=0.0001) impact of combination
      targeted therapy vs. control on cell viability was shown. Results of Quantitative
      Real Time-PCR represented a remarkably decreased (p <=0.0001) expression of the
      studied genes involving in tumorigenicity, metastasis, invasion, and angiogenesis
      (STAT3, IL8, MMP2, MMP9, and VEGF) by targeted combination treatment vs. control.
      Conclusion: The mucin1 aptamer-conjugated chitosan nanoparticles, containing
      docetaxel and cMET siRNA, is suggested for treatment of mucin1+ metastatic breast
      cancer cells. However, further studies should be conducted on animal models.

PMID- 30276136
TI  - Comparison of Pectin Layers for Nicotine Transdermal Patch Preparation.
AB  - Purpose: The objective of the present investigation was to prepare and evaluate
      transdermal patches for nicotine. Methods: Pectin isolated from the hulls of
      Monthong durian or leaves of Krueo Ma Noy was used as a matrix membrane for the
      controlled release of nicotine and compared with commercial pectin. The
      mechanical properties, moisture uptake, and Fourier transform infrared spectra
      were characterized. The in vitro stability of these patches was evaluated and
      compared to commercial nicotine patches. Results: The mechanical properties of
      the patches made from isolated pectin were greater than those prepared from
      commercial pectin; brittle commercial patches were obtained after nicotine
      loading. The moisture uptake of the patches made with isolated pectin was in the
      range of 30.20-44.29%. There was no incompatibility between the ingredients of
      the nicotine transdermal patches or any degradation of the drug. The matrix layer
      made from isolated pectin controlled the nicotine release more effectively than
      did commercial nicotine patches. In addition, these patches were stable at in a
      refrigerator (approximately 4+/-2  degrees C) and at ambient temperature
      (approximately 30+/-2  degrees C) for 3 months, retaining 90% of the loaded
      nicotine. Conclusion: Our study suggests that using isolated pectin as the matrix
      layer should control the release of nicotine from transdermal patches.

PMID- 30276137
TI  - Enhanced Intestinal Permeation of Doxorubicin Using Chitosan Nanoparticles.
AB  - Purpose: Due to limited oral bioavailability of doxorubicin (Dox) many efforts
      during the last decades focused on the development of novel delivery systems to
      overcome these limitations. In the present study, Dox encapsulated chitosan
      nanoparticles were prepared to evaluate the intestinal permeation of Dox via oral
      administration. Methods: Nanoparticles were fabricated based on ionic gelation
      method using tripolyphosphate. Some physicochemical properties, such as
      nanoparticle size and morphology, loading efficiency and in vitro drug release in
      3 different pH values (5.0, 6.8 & 7.4) were evaluated. Intestinal permeations of
      free Dox and Dox loaded in nanoparticles were assessed using rat intestinal sac
      model. Results: The nanoparticles were spherical shape with average size of 150
      +/- 10 nm. The entrapment and loading efficiency of Dox were up to 40% and 23%,
      respectively. According to the release profiles, up to 30% of loaded drug was
      released within 6hrs and the remaining amount of Dox was released more gradually,
      but this pattern was related to pH of the medium. The amount of drug released at
      acidic condition (pH 5.0) was greater than other pHs. The intestinal permeation
      of Dox increased nearly up to 90% by loading in chitosan nanoparticles.
      Conclusion: Using chitosan nanoparticles presents a potential safe drug delivery
      system for oral administration of Dox. In vivo studies and the determined
      pharmacokinetic and pharmacodynamic of Dox loaded chitosan nanoparticles after
      oral administration are planned for future studies.

PMID- 30276138
TI  - Fabrication and Characterization of Gliclazide Nanocrystals.
AB  - Purpose: The main aim of the present investigation was to enhance the solubility
      of poorly soluble Gliclazide by nanocrystallization. Methods: In present
      investigation gliclazide nanocrystals were prepared by sonoprecipitation using
      Pluronic F68, Poly Vinyl Alcohol (PVA), Poly ethylene Glycol 6000 (PEG), Poly
      Vinyl Pyrrolidine (PVP K30) and Sodium Lauryl Sulphate (SLS) as stabilizers.
      Fourier Transform Infrared Spectroscopic study (FTIR), Differential Scanning
      Calorimetry (DSC) and X ray diffraction (XRD) studies were conducted to study the
      drug interactions. Size and zeta potential of the nanocrystals were evaluated. In
      vitro and in vivo studies of nanocrystals were conducted in comparison to pure
      gliclazide. Results: The Gliclazide nanocrystals (GN) showed mean particle size
      of 131+/-7.7 nm with a zeta potential of -26.6 mV. Stable nanocrystals were
      formed with 0.5% of PEG 6000. FTIR, DSC and XRD studies of nanocrystals showed
      absence of interactions and polymorphism. SEM photographs showed a change in
      morphology of crystals from rod to irregular shape. There is an increase in the
      saturation solubility and the percentage drug release from formulation GN5
      (Optimized Gliclazide Nanocrystals) was found to be 98.5 in 15 min. In the in
      vivo study, GN5 nanocrystals have reduced the blood glucose level to 296.4+/-4.26
      mg/dl in 12 hr. The nanocrystals showed lower tmax and higher Cmax values as
      compared to pure gliclazide. Conclusion: The prepared nanocrystals of gliclazide
      were stable without any drug polymer interactions. Increase in the dissolution of
      nanocrystals compared to pure gliclazide and significant reduction in blood
      glucose level in vivo indicated better bioavailability of the nanocrystals.
      Therefore, it is concluded that nanocrystal technology can be a promising tool to
      improve solubility and hence dissolution of a hydrophobic drug.

PMID- 30276139
TI  - Effect of Ghrelin on Caspase 3 and Bcl2 Gene Expression in H2O2 Treated Rat's
      Bone Marrow Stromal Cells.
AB  - Purpose: The antiapoptotic effect of ghrelin in various cell lines including bone
      marrow stromal cells (BMSCs) has been proved. However, the real mechanism of this
      effect is not clear. Caspase3 and Bcl2 are well-known pro- and antiapoptotic
      regulatory genes in eukaryotes. The aim of the study was to find out the effect
      of ghrelin on Caspase 3 and Bcl2 change in BMSCs. Methods: Rat BMSCs were
      cultivated in DMEM. Passage 3 BMSCs were treated with ghrelin 100 MUM for 48 h.
      Real-time PCR for Caspase 3 and Bcl2 was carried out from B (untreated BMSCs), BH
      (BMSCs treated with 125 uM H2O2), BGH (BMSCs treated with 100 uM ghrelin then 125
      uM H2O2) and BG (BMSCs treated with 100 uM ghrelin) groups. For
      immunofluorescence, cells were incubated with anti Caspase 3 and Bcl2monoclonal
      antibodies. Primary antibodies were visualized using the FITC method. All data
      are presented as means +/- SEM. Values of P<0.05 were considered statistically
      significant. Results: Ghrelin decreased mRNA expressions of Caspase-3
      significantly as compared to the BH group (P<0.05). Also, Bcl-2 gene expression
      showed an increment in BG group as compare with BH and BGH groups (P<0.05). A
      high present of Bcl-2 positive cells were observed in the BGH group while Caspase
      3 positive cells were significantly decreased in the BGH group compared with the
      BH group (P<0.05). Conclusion: Ghrelin probably enhances BMSCs viability through
      regulation of pro- and antiapoptotic genes Caspase 3 and Bcl2. However the
      signaling pathway of this effect should be elucidated in the future.

PMID- 30276140
TI  - Snail-1 Silencing by siRNA Inhibits Migration of TE-8 Esophageal Cancer Cells
      Through Downregulation of Metastasis-Related Genes.
AB  - Purpose: Snail-1 is a transcription factor, which takes part in EMT, a process
      related to the emergence of invasion and cancer progression. The purpose of this
      study was to evaluate the effect of Snail-1 silencing on the human esophageal
      squamous cell carcinoma cell line, namely TE-8, in vitro. Methods: In this study,
      transfection of Snail-1 specific siRNA was conducted into TE-8 cells. The
      relative mRNA expression levels of Snail-1, Vimentin, CXCR4 and MMP-9 and
      transcription levels of miR-34a and let-7a were investigated by quantitative Real
      time PCR. Western blotting was carried out to evaluate the Snail-1 protein level.
      Migration assay of TE-8 cells was also performed following the presence or
      absence of Snail-1 specific siRNA. MTT and TUNEL assays were performed to
      evaluate cell viability after Snail-1 silencing. Results: It was found that
      treatment of cancer cells with the Snail-specific siRNA effectively downregulated
      the expression of Snail-1 in both mRNA and protein levels, and vimentin, CXCR4,
      and MMP-9 in mRNA level. However, it elevated the transcript levels of miR-34a
      and let-7a expressions. Furthermore, transfection of cancer cells with the Snail
      specific siRNA significantly induced apoptosis in TE8 cells. Moreover,
      suppression of Snail-1 led to diminished cell migration. Conclusion: It seems
      that Snail-specific siRNA can significantly interrupt esophageal cancer cell
      migration and reduce metastatic-related factors and induce miR-34a and let-7a in
      vitro. The bottom line is that therapeutic approaches via targeting Snail-1 can
      be used for ESCC treatment, suggesting that other possible target molecules for
      ESCC therapy require to be explored.

PMID- 30276141
TI  - Simulation and Stability Assessment of Anti-EpCAM Immunotoxin for Cancer Therapy.
AB  - Purpose: Epithelial cell adhesion molecule (EpCAM) is a dominant antigen in human
      colon carcinoma tissue. Topology features of this antigen are different in normal
      and malignant conditions; for instance, EpCAM is much less accessible to
      antibodies in normal cells than in cancerous tissues. Hence, EpCAM has been
      considered as a suitable candidate for cancer target therapy via immunotoxins
      (ITs) development. In this study, attention was focused on the stability
      assessment of anti-EpCAM-IT (anti-Ep-IT) to design a novel IT. Methods: The 3D
      structures of the antibody template and the toxin segment of anti-Ep-IT were
      retrieved from PDB. Discovery Studio3.0 was used to separate the ligands and
      water molecules. The antibody (Ab) fragment of anti-Ep-IT was aligned using
      protein blast (BLAST-p), and SWISS-MODEL database was used for Ab modeling. IT
      modeling was accomplished using MODELLER 9.15. Also, GROMACS 5.07 was used for
      molecular dynamic (MD) simulation step. Moreover, ERRAT and RAMPAGE databases
      were used for quality assessment of the structures. Results: BLAST-p results
      indicated that antibody moiety of IT has the highest E-value and query coverage
      scores to the monoclonal antibody (mAb) 4D5MOC-B. Modeling by SWISS-MODEL
      provided a reasonable template for Ab portion compared to MODELLER. The best
      modeled full-length IT with the lowest RMSD values was selected. Finally, RMSD
      plot for MD stage demonstrated constant values from 7000ps to 20000ps.
      Conclusion: In general, both modeling results and their quality evaluations were
      satisfactory for designing IT. Moreover, RMSD plot revealed that IT stability was
      preserved during the simulation. Overall, our findings led to modeling and
      simulation of the anti-Ep-IT with more structural stability.

PMID- 30276142
TI  - Mummy Material Can Promote Differentiation of Adipose Derived Stem Cells into
      Osteoblast through Enhancement of Bone Specific Transcription Factors Expression.
AB  - Purpose: Application of Mummy material for treatment of different diseases such
      as bone fracture, cutaneous wounds and joint inflammation has been advised since
      hundred years ago in Persian traditional medicine. Due to the claims of
      indigenous people and advice of traditional medicine for application of this
      material in healing of bone fractures, this study has been designed to evaluate
      whether Mummy material can promote the differentiation of mesenchymal stem cells
      into osteoblasts and enhance the expression of bone specific genes and proteins.
      Methods: Adipose derived stem cells (ASCs) at fourth cell passage were divided
      into control, osteogenesis group (received osteogenic medium), Mummy group
      (received Mummy at concentration of 500 ug/ml). ASCs in the fourth group were
      treated with both osteogenic medium and Mummy (500ug/ml). Cells in all groups
      were harvested on days 7, 14 and 21 days for further evaluation through Real time
      RT-PCR, Von kossa staining, Immunocytochemistry and flowcytometery. Results:
      Treatment of ASCs with Mummy at concentration of 500ug/ml promotes the expression
      level of Osteocalcin, RUNX-2 and beta1-integrin genes in different time points
      but that of the Osterix did not changed. Furthermore the expression of
      Osteocalcin protein enhanced significantly in ASCs treated with Mummy detected by
      Immunocytochemistry and flowcytometery technique compared to the control groups.
      The results of this study also showed that treatment of ASCs with Mummy resulted
      in formation of mineral deposits which was evaluated by Von Kossa staining
      method. Conclusion: Obtained data from this study reveals that Mummy is a potent
      enhancer for differentiation of ASCs into osteoblasts in in vitro system,
      probably through increasing the level of bone specific genes and proteins.

PMID- 30276143
TI  - Dual Preconditioning: A Novel Strategy to Withstand Mesenchymal Stem Cells
      against Harsh Microenvironments.
AB  - Purpose: Poor survival rate of mesenchymal stem cells (MSCs) following their
      transplantation is one of the major challenges in their therapeutic application.
      Therefore, it is necessary to augment the viability of the MSCs in order to
      improve their therapeutic efficacy. Several strategies have been used to overcome
      this problem. Preconditioning of MSCs with oxidative stresses has gained a lot of
      attention. Therefore, in the present study, we investigated the effects of
      simultaneous preconditioning of MSCs with hydrogen peroxide and serum deprivation
      stresses on their survival and resistance to stressful conditions. Methods: MSCs
      were isolated from human umbilical cord blood. To perform simultaneous
      preconditioning, the cells were cultured in DMEM medium containing 1, 2.5 and 5
      percent FBS and different concentrations of H2O2 (5, 10, 15, 20, 25, 30, 35, 40,
      50, 60, 80 and 100 uM) for 24 hrs. Then, the cells were cultured in recovery
      culture medium. Finally, one group of the cells was exposed to a lethal
      concentration of H2O2 (300uM), and the other cells were cultivated in FBS free
      DMEM medium as the lethal situation. In addition, the percentage of apoptotic
      cells was analyzed using Caspase 3 assay kit. Results: Simultaneous
      preconditioning of the MSCs with 15uM H2O2 plus serum deprivation, 2.5% FBS,
      significantly increased the resistance of the cells to the toxicity induced
      following their cultivation in FBS free DMEM medium. It exerted the protective
      effect on the cells after treating with the lethal dose of H2O2 as well.
      Conclusion: Simultaneous preconditioning of MSCs with oxidative and serum
      deprivation stresses enhances their survival against harsh conditions, which
      might increase the viability and stability of the MSCs following their
      transplantation.

PMID- 30276144
TI  - Impact of Omega-3 Supplementation on High Sensitive C-Reactive Protein Level and
      30-Day Major Adverse Cardiac Events After the Implementation of Coronary Stent in
      Patients with Chronic Kidney Disease: A Randomized Clinical Study.
AB  - Purpose: Studies have revealed that patients with chronic kidney disease (CKD)
      are more susceptible to adverse effects of percutaneous coronary intervention
      (PCI). In addition, the role of elevated high sensitive C-reactive protein (hs
      CRP) in the prediction of adverse cardiac outcomes after coronary stent
      implantation has already been shown. Therefore, in this study, we aimed to
      evaluate the effect of omega-3 supplementation on hs-CRP and 30-day major adverse
      cardiac events (MACE) in patients with CKD undergoing elective PCI. Methods: In
      this randomized trial, 80 CKD patients who were candidates for elective PCI, were
      randomly assigned to two groups; the first group received a single dose of omega
      3 (2500 mg, 12 h before PCI) as well as the standard drug regimen of PCI and the
      second group received placebo plus the standard therapy (325 mg loading dose of
      aspirin, 600 mg loading dose of clopidogrel, and weight-adjusted intravenous
      heparin). Hs-CRP levels were measured at baseline and 24 h after the intervention
      as a primary endpoint. The secondary endpoint was the incidence of MACE over a 30
      day period after PCI. Results: Omega-3 did not significantly decrease post-PCI
      serum level of hs-CRP; however, the overall 30-day MACE was significantly lower
      in the omega-3 group compared to the control group (p=0.05). Conclusion: Our
      results revealed the positive effect of the omega-3 supplement on decreasing 30
      day MACE; hence, omega-3 may be considered as an effective adjunctive therapy to
      the standard drug regimen used before PCI. The evaluation of the effect of omega
      3 on long-term MACE is recommended for future studies.

PMID- 30276145
TI  - Oleoylethanolamide Supplementation Reduces Inflammation and Oxidative Stress in
      Obese People: A Clinical Trial.
AB  - Purpose: Obesity as a serious public health problem worldwide, results in the
      incidence of many chronic diseases. Obesity has been recognized as a chronic low
      grade inflammation disorder. Altered endocannabinoid system tone is also involved
      in the pathogenesis of obesity. The present study aimed to investigate the
      effects of oleoylethanolamide supplementation on inflammatory biomarkers and
      oxidative stress in obese people. Methods: This randomized, double-blind, placebo
      controlled clinical trial was carried out on 60 healthy obese people in 2016 in
      Tabriz, Iran. Eligible subjects were randomly divided into intervention (received
      daily, two 125 mg OEA capsules) and control groups (the same amounts of starch)
      and treated for 8 weeks. Blood samples (5 ml) were taken in fasting state at the
      baseline and at the end of the study. The concentrations of MDA and TAS were
      measured using a spectrophotometer. A high sensitive-C reactive protein level was
      measured by Immunoturbidimetry assay using the commercial kit. IL-6 and TNF-alpha
      levels were assayed by the ELISA method. The differences between groups were
      assessed by ANCOVA and statistical significance was determined at p<0.05.
      Results: Analysis was done on 56 participants who continued intervention until
      the end of the study. A significant decrease in the IL-6 and TNF-alpha serum
      concentrations was observed in the intervention group (p<0.001). Changes in other
      variables were undetectable (p>0.05). Conclusion: The use of OEA as a
      complementary pharmacotherapy agent could be effective in improving inflammation
      and oxidative stress in obese people. Future studies are needed to confirm the
      obtained results.

PMID- 30276146
TI  - Evaluation of NPP1 as a Novel Biomarker of Coronary Artery Disease: A Pilot Study
      in Human Beings.
AB  - Purpose: Coronary artery calcification (CAC) is utilized as an important tool for
      global risk assessment of cardiovascular events in individuals with intermediate
      risk. Ecto phosphodiesterase/nucleotide phosphohydrolase-1(ENPP1) converts
      extracellular nucleotides into inorganic pyrophosphate and it is a key regulator
      of tissue calcification that adjusts calcification in tissues like vascular
      smooth muscle cells. The main purpose of this clinical study was to find out the
      correlation between ENPP1 serum concentration and CAC in human for the first
      time. Methods: In this study 83 patients (16 diabetic patients and 67 non
      diabetic patients) with coronary artery disease who fulfilled inclusion and
      exclusion criteria, entered the study. For all patients a questionnaire
      consisting demographic data and traditional cardiovascular risk factors were
      completed. Computed tomography (CT)-Angiography was carried out to determine
      coronary artery calcium score and enzyme-linked immunosorbent assay (ELISA)
      method was used for measuring ENPP1 serum concentrations. Results: There was a
      reverse significant correlation between ENPP1 serum concentration and total CAC
      score and also CAC of right coronary artery (RCA) (P<0.05) in non-diabetic
      patients. Conclusion: On the basis of our results, ENPP1 serum concentration may
      be a suitable biomarker for coronary artery disease at least in non-diabetic
      patients. However, more studies with higher sample size are necessary for its
      confirmation.

PMID- 30276147
TI  - Determining Abuse Deterrence Performance of Poly (ethylene oxide) Using a
      Factorial Design.
AB  - Purpose: The purpose of this study was to determine the effects of thermal
      processing and antioxidant formulation variables on the abuse deterrence
      performance of a high molecular weight poly(ethylene oxide) (PEO) polymer.
      Methods: A 24 factorial design with one categorical factor (antioxidant type) and
      three continuous factors (curing time, curing temperature, % antioxidant) was
      used. Abuse deterrence performance was evaluated using solution viscosity,
      surface melting temperature, and mechanical strength. Thermal degradation of PEO
      powders before compaction was also studied using DSC, FTIR spectroscopy, and
      viscosity analysis. Results: Our results showed that curing temperature and type
      of antioxidant can significantly affect the deterrence performance of PEO. The
      main effect plot for viscosity shows the most prominent factors affecting
      viscosity are curing temperature and type of antioxidant. However, curvature in
      the linear model obtained was not sufficient to completely describe the behavior.
      For surface melting temperature, butylated hydroxytoluene was associated with
      higher surface melting temperatures compared to ascorbic acid. Additionally,
      higher percent of antioxidant resulted in higher melting temperature. Particle
      size distribution to indicate mechanical strength showed no significant effects
      of tested factors. This suggests that comminution method has more prominent
      effect on tablet fragment size than the formulation and processing factors
      studied. Conclusion: While heat confers the mechanical strength to the polymer,
      it can diminish its physical stability and solution state viscosity. The
      experimental studies showed that prolonged exposure to high temperatures, even in
      the presence of antioxidants, can severely hamper polymer deterrence performance
      in both solid and solution states.

PMID- 30276148
TI  - The Cytotoxic and Antimigratory Activity of Brazilin-Doxorubicin on MCF-7/HER2
      Cells.
AB  - Purpose: Breast cancer cells with overexpression of HER2 are known to be more
      aggressive, invasive, and resistant to chemotherapeutic agent. Brazilin, the
      major compound in the Caesalpinia sappan L. (CS) heartwood, has been studied for
      it's anticancer activity. The purpose of this study was to investigate the
      cytotoxic and antimigratory activity of brazilin (Bi) in combination with
      doxorubicin (Dox) on MCF-7/HER2 cells. Methods: Cytotoxic activities of Bi
      individually and in combination with Dox were examined by MTT assay. Synergistic
      effects were analyzed by combination index (CI). Apoptosis and cell cycle
      profiles were observed by using flow cytometry. Migrating and invading cells were
      observed by using a Boyden chamber assay. Levels of MMP2 and MMP9 activity were
      observed by using a gelatin zymography assay. Levels of HER2, Bcl-2, Rac1, and
      p120 protein expression were observed by using an immunoblotting assay. Results:
      The results of the MTT assay showed that Bi inhibited MCF-7/HER2 cell growth in a
      dose-dependent manner with an IC50 of 54 +/- 3.7 uM. Furthermore, the combination
      of Bi and Dox showed a synergistic effect (CI <1). Flow cytometric analysis of Bi
      and its combination with Dox showed cellular accumulation in the G2/M phase and
      induction of apoptosis through suppression of Bcl-2 protein expression. In the
      Boyden chamber assay, gelatin zymography, and subsequent immunoblotting assay,
      the combination Bi and Dox inhibited migration, possibly through downregulation
      of MMP9, MMP2, HER2, Rac1, and p120 protein expression. Conclusion: We conclude
      that Bi enhanced cytotoxic activity of Dox and inhibited migration of MCF-7/HER2
      cells. Therefore, we believe that it has strong potential to be developed for the
      treatment of metastatic breast cancer with HER2 overexpression.

PMID- 30276149
TI  - Presynaptic Activity of an Isolated Fraction from Rhinella schneideri Poison.
AB  - Purpose: Rhinella schneideri is a toad found in many regions of the South
      America. The poison of the glands has cardiotoxic effect in animals and
      neuromuscular effects in mice and avian preparation. The purpose of this work was
      to identify the toxin responsible for the neuromuscular effect in avian and mice
      neuromuscular preparation. Methods: The methanolic extract from R. schneideri
      poison was fractioned by reversed phase HPLC. The purity and molecular mass were
      determined by LC/MS mass spectrometry. Chick biventer cervicis and mouse phrenic
      nerve diaphragm were used as neuromuscular preparations to identify the toxin.
      Results: The purification resulted in 32 fractions, which 4 of them were active
      in neuromuscular preparation. The toxin of fraction 20 were chosen for better
      reproducibility of the whole extract activity and its molecular mass was 730.6
      Da. The toxin produced facilitation of the muscle contraction followed by a
      complete neuromuscular blockade in chick biventer cervicis preparation in 90 min
      without interfering with the exogenous response to ACh and KCl. The quantal
      content was increased from 128 +/- 13 (control) to 216 +/- 44 (after 5 min and
      sustained until 60 min) in the presence of the toxin. Conclusion: In conclusion,
      our results demonstrated that the neuromuscular action of the poison of Rhinella
      schneideri is a multitoxin effect. More, the present work first isolated a 730.6
      Da toxin that better represent the whole poison neuromuscular effect, to which is
      attributed a presynaptic action in avian and mouse neuromuscular preparation.

PMID- 30276150
TI  - Astaxanthin-Rich Haematococcus pluvialis Algal Hepatic Modulation in D-Galactose
      Induced Aging in Rats: Role of Nrf2.
AB  - Purpose: Aging is associated with hepatic morphological and physiological
      deterioration due to the accumulation of endogenous and exogenous free radicals
      and the resultant oxidative stress. The present study aims to investigate the
      effect of Haematococcus pluvialis microalgae on hepatic changes associated with D
      galactose (D-Gal)-induced aging in rats. Methods: Aging was induced in rats by
      daily intraperitoneal injection of D-Gal (200 mg/kg/day) for eight consecutive
      weeks. D-Gal-injected rats were treated by astaxanthin (ATX)-rich H. pluvialis
      biomass, its carotenoid and polar fractions for two weeks. Twenty four hours
      after the last dose, blood samples were collected and the liver tissues were
      isolated for further biochemical and histopathological examinations. Results: D
      Gal induced aging was associated with an elevation in serum liver function
      parameters, hepatic oxidative stress biomarkers viz., catalase (CAT), glutathione
      transferase (GST) and myeloperoxidase (MPO), as well as decreased expression of
      nuclear factor like-2 (Nrf2). Moreover, induction of aging exhibited an elevation
      of hepatic inflammatory cytokine; interleukin-6 (IL-6) and its modulator; nuclear
      factor Kappa B (NF-KB). However, treatment of D-Gal injected rats with ATX-rich
      H. pluvialis restored the serum liver function parameters as well as hepatic CAT,
      GST and MPO levels with an elevated expression of Nrf2. Treatment with ATX-rich
      H. pluvialis was also accompanied with a decrease in hepatic levels of NF-KB and
      IL-6. Histopathological examination emphasized all the previous results.
      Similarly, all trans-astaxanthin showed high affinity towards Nrf2 with -7.93
      kcal/mol estimated free energy of binding as well as moderate affinities towards
      IL-6 and NF-KB through a docking study. Conclusion: ATX-rich H. pluvialis showed
      beneficial effects by ameliorating the hepatic changes associated with D-Gal
      induced aging in rats due to its modulatory role of the Nrf2/Keap pathway.

PMID- 30276151
TI  - The efficacy of ultrasonography in monitoring the healing of jaw lesions.
AB  - Purpose: This study aimed to assess the reliability of ultrasonography (US) in
      comparison with cone-beam computed tomography (CBCT) as a tool for monitoring the
      healing of jaw lesions. Materials and Methods: Twenty-one radiolucent lesions in
      jaws referred to the Oral Surgery Department at our institution were selected for
      this study. All lesions underwent CBCT and US examinations. The anteroposterior,
      superoinferior, and mesiodistal dimensions of the lesions were measured on CBCT
      and US images before surgery and at 6 months after surgery. The dimensions were
      compared between the US and CBCT images. Blood-flow velocity around the lesions
      was measured by color Doppler before surgery and at 1 week and 6 months after
      surgery to assess the capability of US to show changes in blood-flow velocity
      around the lesion. Results: Before surgery, there were no significant differences
      between US and CBCT in the mesiodistal and anteroposterior dimensions, although a
      significant difference was found in the superoinferior dimension (P<.05).
      However, at 6 months after surgery, significant differences were found between US
      and CBCT in all dimensions, and it is likely that the US measurements more
      accurately reflected the extent of healing. The average blood-flow velocity
      increased at 1 week after surgery (5.84 cm/s) compared with the velocity before
      surgery (4 cm/s) (P<.05). Then, at 6 months after surgery, the blood-flow
      velocity significantly decreased (3.53 cm/s) compared to the velocity measured at
      1 week after surgery (P<.05). Conclusion: US with color Doppler was confirmed to
      be a more efficient tool than CBCT for monitoring bone healing.

PMID- 30276152
TI  - Usefulness of shear wave elastography in the diagnosis of oral and maxillofacial
      diseases.
AB  - Purpose: To evaluate the usefulness of shear wave elastography in the diagnosis
      of oral and maxillofacial diseases. Materials and Methods: Ten patients with oral
      and maxillofacial diseases and 28 volunteers drawn from our student doctors were
      examined by shear wave elastography with a 14-MHz linear transducer using an
      Aplio 300 apparatus (Canon Medical Systems, Otawara, Japan). A statistical
      analysis of the shear elastic modulus (kPa) of healthy tissue (the sublingual
      gland, submandibular gland, anterior belly of the digastric muscle, and
      geniohyoid muscle) in the 28 volunteers was performed using 1-way repeated
      measures analysis of variance with the Tukey honest significant difference test.
      The maximum shear elastic modulus (kPa) of 8 patients with squamous cell
      carcinoma (SCC) and 2 patients with benign lesions was evaluated with the Mann
      Whitney U test. The analysis used a 5% significance level. Results: The mean
      shear elastic modulus of the sublingual gland (9.4+/-3.7 kPa) was lower than that
      of the geniohyoid muscle (19.2+/-9.2 kPa, P=.000) and the anterior belly of the
      digastric muscle (15.3+/-6.1 kPa, P=.004). The maximum shear elastic modulus of
      the SCCs (109.6+/-14.4 kPa) was higher than that of the benign lesions (46.4+/
      26.8 kPa, P=.044). Conclusion: Our results demonstrated the usefulness of shear
      wave elastography in the diagnosis of oral and maxillofacial diseases. Shear wave
      elastography has the potential to be an effective technique for the objective and
      quantitative diagnosis of oral and maxillofacial diseases.

PMID- 30276153
TI  - Application of portable digital radiography for dental investigations of ancient
      Egyptian mummies during archaeological excavations: Evaluation and discussion of
      the advantages and limitations of different approaches and projections.
AB  - Purpose: In the age of X-ray computed tomography (CT) and digital volume
      tomography (DVT), with their outstanding post-processing capabilities,
      indications for planar radiography for the study of the dentition of ancient
      Egyptian mummies may easily be overlooked. In this article, the advantages and
      limitations of different approaches and projections are discussed for planar oral
      and maxillofacial radiography using portable digital X-ray equipment during
      archaeological excavations. Furthermore, recommendations are provided regarding
      projections and sample positioning in this context. Materials and Methods: A
      total of 55 specimens, including 19 skeletonized mandibles, 14 skeletonized
      skulls, 18 separate mummified heads, and 4 partially preserved mummies were
      imaged using portable digital X-ray equipment in the course of archaeological
      excavations led by the University of Basel in the Valley of the Kings between
      2009 and 2012. Images were evaluated by 2 authors with regard to the visibility
      of diagnostically relevant dental structures using a 4-point grading system
      (Likert scale). Results: Overall, the visibility of diagnostically relevant
      dental structures was rated highest by both authors on X-ray images acquired
      using a dental detector. The tube-shift technique in the lateral projections of
      mandibular dentition achieved the second-best rating, and lateral projections
      achieved the third-best rating. Conclusion: Conventional planar digital X-ray
      imaging, due to its ubiquity, remains an excellent method-and often the only
      practicable one-for examining the skulls and teeth of ancient Egyptian mummies
      under field conditions. Radiographic images of excellent diagnostic quality can
      be obtained, if an appropriate methodology regarding the selected projections and
      sample placement is followed.

PMID- 30276154
TI  - Influence of voxel size on cone-beam computed tomography-based detection of
      vertical root fractures in the presence of intracanal metallic posts.
AB  - Purpose: This study was performed to evaluate the influence of voxel size and the
      accuracy of 2 cone-beam computed tomography (CBCT) systems in the detection of
      vertical root fracture (VRF) in the presence of intracanal metallic posts.
      Materials and Methods: Thirty uniradicular extracted human teeth were selected
      and randomly divided into 2 groups (VRF group, n=15; and control group, n=15).
      The VRFs were induced by an Instron machine, and metallic posts were placed in
      both groups. The scans were acquired by CBCT with 4 different voxel sizes: 0.1 mm
      and 0.16 mm (for the Eagle 3D V-Beam system) and 0.125 mm and 0.2 mm (for the i
      CAT system) (protocols 1, 2, 3, and 4, respectively). Interobserver and
      intraobserver agreement was assessed using the Cohen kappa test. Sensitivity and
      specificity were evaluated and receiver operating characteristic analysis was
      performed. Results: The intraobserver coefficients indicated good (0.71) to very
      good (0.83) agreement, and the interobserver coefficients indicated moderate
      (0.57) to very good (0.80) agreement. In respect to the relationship between
      sensitivity and specificity, a statistically significant difference was found
      between protocols 1 (positive predictive value: 0.710, negative predictive value:
      0.724) and 3 (positive predictive value: 0.727, negative predictive value: 0.632)
      (P<.05). The least interference due to artifact formation was observed using
      protocol 2. Conclusion: Protocols with a smaller voxel size and field of view
      seemed to favor the detection of VRF in teeth with intracanal metallic posts.

PMID- 30276155
TI  - Location and shape of the mandibular lingula: Comparison of skeletal class I and
      class III patients using panoramic radiography and cone-beam computed tomography.
AB  - Purpose: The aim of this study was to compare the location and the shape of the
      mandibular lingula in skeletal class I and III patients using panoramic
      radiography and cone-beam computed tomography. Materials and Methods: The sample
      group included 190 skeletal class I patients and 157 class III patients. The
      location of the lingula in relation to the deepest point of the coronoid notch
      was classified into 3 types using panoramic radiographs. The shapes of the
      lingulae were classified into nodular, triangular, truncated, or assimilated
      types using cone-beam computed tomographic images. The data were analyzed using
      the chi-square test. Results: The tips of the lingulae were at the same level as
      the coronoid notch in 75.3% of skeletal class I patients and above the coronoid
      notch in 66.6% of class III patients. The positions of the lingulae in relation
      to the deepest point of the coronoid notch showed statistically significant
      differences between class I and class III patients. The most common shape was
      nodular, and the least common was the assimilated shape. Although this trend was
      not statistically significant, the triangular shape was more frequently observed
      in class III patients than in class I patients. Conclusion: The locations and the
      shapes of the mandibular lingulae were variable. Most of the lingulae were at the
      same level as the coronoid notch in skeletal class I patients and above the
      coronoid notch in skeletal class III patients. The nodular and assimilated-shaped
      lingulae were the most and the least prevalent, respectively.

PMID- 30276156
TI  - A novel classification of anterior alveolar arch forms and alveolar bone
      thickness: A cone-beam computed tomography study.
AB  - Purpose: This study classified alveolar arch forms and evaluated differences in
      alveolar bone thickness among arch forms in the anterior esthetic region using
      cone-beam computed tomography (CBCT) images. Materials and Methods: Axial views
      of 113 CBCT images were assessed at the level of 3 mm below the cementoenamel
      junction (CEJ) of the right and left canines. The root center points of teeth in
      the anterior esthetic region were used as reference points. Arch forms were
      classified according to their transverse dimensions and the intercanine width-to
      depth ratio. The buccolingual alveolar bone thickness of each tooth was measured
      at 3 mm below the CEJ and at the mid-root level. Differences in the mean
      thicknesses among arch forms were analyzed. Results: Anterior maxillary arches
      could be classified as long narrow, short medium, long medium, and long wide
      arches. Significant differences in buccolingual alveolar bone thickness among the
      arch groups were found at both levels. The long wide arches presented the
      greatest bone thickness, followed by the long medium arches, while the long
      narrow and short medium arches were the thinnest. Conclusion: Arch forms were
      classified as long narrow, short medium, long medium, and long wide. The
      buccolingual alveolar bone thickness exhibited significant differences among the
      arch forms.

PMID- 30276157
TI  - A comparative study of cone-beam computed tomography and digital panoramic
      radiography for detecting pulp stones.
AB  - Purpose: The aim of this study was to compare cone-beam computed tomography
      (CBCT) and digital panoramic radiography (DPR) for the detection of pulp stones.
      Materials and Methods: DPR and CBCT images of 202 patients were randomly selected
      from the database of our department. All teeth were evaluated in sagittal, axial,
      and coronal sections in CBCT images. The systemic condition of patients, the
      presence of pulp stones, the location of the tooth, the group of teeth, and the
      presence and depth of caries and restorations were recorded. The presence of pulp
      stones in molar teeth was compared between DPR and CBCT images. Results: Pulp
      stones were identified in 105 (52.0%) of the 202 subjects and in 434 (7.7%) of
      the 5,656 teeth examined. The prevalence of pulp stones was similar between the
      sexes and across various tooth locations and groups of teeth (P>.05). A positive
      correlation was observed between age and the number of pulp stones (rho=0.277,
      P<.01). Pulp stones were found significantly more often in restored or carious
      teeth (P<.001). CBCT and DPR showed a significant difference in the detection of
      pulp stones (P<.001), which were seen more often on DPR than on CBCT. Conclusion:
      DPR, as a 2D imaging system, has inherent limitations leading to the
      misinterpretation of pulp stones. Restored and carious teeth should be carefully
      examined for the presence of pulp stones. CBCT imaging is recommended for a
      definitive assessment in cases where there is a suspicion of a pulp stone on DPR.

PMID- 30276158
TI  - The relationship between masseter muscle thickness measured by ultrasonography
      and facial profile in young Korean adults.
AB  - Purpose: The purpose of this study was to evaluate the relationship between
      masseter muscle thickness, facial morphology, and mandibular morphology in Korean
      adults using ultrasonography. Materials and Methods: Ultrasonography was used to
      measure the masseter muscle thickness bilaterally of 40 adults (20 males, 20
      females) and was performed in the relaxed and contracted states. Facial photos
      and panoramic radiography were used for morphological analyses and evaluated for
      correlations with masseter muscle thickness. We also evaluated the correlations
      of age, body weight, stature, and body constitution with masseter muscle
      thickness. Results: In the relaxing, the masseter was 9.8+/-1.3 mm in females and
      11.3+/-1.2 mm in males. In the contracted state, it was 12.4+/-1.4 mm in females
      and 14.7+/-1.4 mm in males. Facial photography showed that bizygomatic facial
      width over facial height was correlated with masseter muscle thickness in both
      sexes in the relaxed state, and was statistically significantly correlated with
      masseter muscle thickness in males in the contracted state. In panoramic
      radiography, correlations were found between anterior angle length and posterior
      angle length and masseter muscle thickness in females, and between body length
      and posterior angle length, between anterior angle length and body length,
      between ramal length and body length, and between body length and condyle length
      in males. Conclusion: Masseter muscle thickness was associated with facial and
      mandibular morphology in both sexes, and with age in males. Ultrasonography can
      be used effectively to measure masseter muscle thickness.

PMID- 30276159
TI  - Multiple intraosseous cervical pneumatocysts: A case report of a rare incidental
      finding on cone-beam computed tomography.
AB  - This report presents a case of cervical pneumatocysts as an incidental finding on
      cone-beam computed tomography. Pneumatocysts are gas-containing lesions of
      unknown etiology. They usually present in the ilium or sacrum, adjacent to the
      sacroiliac joint. In the literature, 21 case reports have described cervical
      pneumatocysts. Cervical pneumatocysts should be differentiated from other
      lesions, such as osteomyelitis, osteonecrosis, and neoplasms, as well as post
      traumatic and post-surgical cases. Computed tomography, cone-beam computed
      tomography, and magnetic resonance imaging are appropriate tools to diagnose
      cervical pneumatocysts.

PMID- 30276160
TI  - Radiographic study of dermal fillers in the facial area: A series of 3 cases.
AB  - In recent years, as interest in maintaining beauty and a youthful appearance has
      grown, filler procedures such as soft tissue augmentation have become more
      popular. These fillers are sometimes seen as radiopaque shadows on radiographic
      images, either due to the fillers themselves or because of secondary reactions;
      such findings may present a diagnostic challenge to dentists. The present report
      describes 3 cases of dermal fillers observed in panoramic and cone-beam computed
      tomographic (CBCT) images. All 3 elderly female patients had filler injected into
      their cheeks and chin area for cosmetic purposes decades ago. On panoramic
      images, multiple symmetric radiopacities were observed in the facial area; on
      CBCT, these calcifications were seen in the subcutaneous tissue in various shapes
      and with varying density. In conclusion, dentists should be aware of the imaging
      characteristics of dermal filler, and should be able to differentiate dermal
      filler from other pathological findings.

PMID- 30276163
TI  - Hydroxyapatite from Fish for Bone Tissue Engineering: A Promising Approach.
AB  - Natural or synthetic hydroxyapatite (HA) has been frequently used as implant
      materials for orthopaedic and dental applications, showing excellent bioactivity,
      adequate mechanical rigidity and structure, osteoconductivity and angiogenic
      properties, no toxicity, and absence of inflammatory or antigenic reactions. HA
      can be easily synthesized or extracted from natural sources, such as bovine bone.
      However, the manufacturing costs to obtain HA are high, restricting the therapy.
      Herein, much effort has been paid for obtaning alternative natural sources for
      HA. The potential of HA extracted from skeleton of animals has been investigated.
      The aim of this review is to exploit the potential of HA derived from fish to
      fulfill biological activities for bone tissue engineering. In particular, HA from
      fish is easy to be manufactured regarding the majority of protocols that are
      based on the calcination method. Furthermore, the composition and structure of HA
      from fish were evaluated; the biomaterial showed good biocompatibility as a
      result of non-cytotoxicity and handling properties, demonstrating advantages in
      comparison with synthetic ones. Interestingly, another huge benefit brought by HA
      from bone fish is its positive effect for environment since this technique
      considerably reduces waste. Certainly, the process of transforming fish into HA
      is an environmentally friendly process and stands as a good chance for reducing
      costs of treatment in bone repair or replacement with little impact into the
      environment.

PMID- 30276162
TI  - Bone Marrow Derived Mesenchymal Stem Cells in Addiction Related Hippocampal
      Damages.
AB  - The brain is an important organ that controls all sensory and motor actions,
      memory, and emotions. Each anatomical and physiological modulation in various
      brain centers, results in psychological, behavioral, and sensory-motor changes.
      Alcohol and addictive drugs such as opioids and amphetamines have been shown to
      exert a great impact on brain, specifically on the hippocampus. Emerging evidence
      has indicated that altered hippocampal neurogenesis is associated with the
      pathophysiology of neuropsychological disorders including addiction. The
      addictive drugs impair neurogenesis and undermine the function of neural
      stem/progenitor cells in hippocampus. This feature was claimed to be one of the
      underlying mechanisms of behavioral changes in patients with addiction. As the
      impairment of stem cells' function has been proven to be the underlying cause of
      pathologic neuroadaptations in the brain, the administration of stem cell
      populations has shown promising results for re-modulating of neuronal status in
      the brain and especially in the hippocampus. Among the different types of stem
      cells, bone marrow derived mesenchymal stem cells are the most proper candidates
      for stem cell therapies. In this review article, the recent studies on the
      effects of addictive drugs on brain neurogenesis, and also the promising
      potential effects of stem cells in curing addiction related hippocampal damages
      are discussed.

PMID- 30276161
TI  - Effects of Metabolites Derived From Gut Microbiota and Hosts on Pathogens.
AB  - Intestinal metabolites participate in various physiological processes, including
      energy metabolism, cell-to-cell communication, and host immunity. These
      metabolites mainly originate from gut microbiota and hosts. Although many host
      metabolites are dominant in intestines, such as free fatty acids, amino acids and
      vitamins, the metabolites derived from gut microbiota are also essential for
      intestinal homeostasis. In addition, some metabolites are only generated and
      released by gut microbiota, such as bacteriocins, short-chain fatty acids, and
      quorum-sensing autoinducers. In this review, we summarize recent studies
      regarding the crosstalk between pathogens and metabolites from different sources,
      including the influence on bacterial development and the activation/inhibition of
      immune responses of hosts. All of these functions would affect the colonization
      of and infection by pathogens. This review provides clear ideas and directions
      for further exploring the regulatory mechanisms and effects of metabolites on
      pathogens.

PMID- 30276165
TI  - The Growth Arrest-Specific Transcript 5 (GAS5) and Nuclear Receptor Subfamily 3
      Group C Member 1 (NR3C1): Novel Markers Involved in Multiple Sclerosis.
AB  - Recent studies have revealed that long noncoding RNAs (lncRNAs) are connected
      with pathogenesis of neurodegenerative diseases. Additionally, glucocorticoids
      have fundamental regulatory roles on the immune system, and act as potent
      therapeutic compounds for autoimmune and inflammatory diseases. The long
      noncoding RNA growth arrest-specific 5 (GAS5) which accumulates inside the cells
      in response to cellular starvation/growth arrest, acts as a potent repressor of
      the glucocorticoid receptor (GR) through its glucocorticoid response element
      (GRE). The aim of the present study was to investigate the role of lncRNA GAS5
      and its downstream target Nuclear Receptor Subfamily 3 Group C Member 1(NR3C1) in
      the pathogenesis of multiple sclerosis (MS), and to define the role of GAS5 in
      the regulation of NR3C1 expression. Quantitative polymerase chain reaction was
      performed for investigating the expression of GAS5 and NR3C1 in MS patients and
      healthy subjects. We found that GAS5 levels were up-regulated in the MS patients,
      blood compared with healthy subjects in correlation with NR3C1 expression. Our
      findings suggest that GAS5 may play on important role in the molecular etiology
      and treatment of MS.

PMID- 30276166
TI  - Circulatory YKL-40 & NLR: Underestimated Prognostic Indicators in Diffuse Glioma.
AB  - In addition to histopathological parameters, evaluation of associated
      hematological factors is essential for devising a sensitive prognostic scale in
      glioma. Increased neutrophil-lymphocyte ratio (NLR), a marker of systemic
      inflammatory response, has recently been associated with worse outcome in various
      cancers. Given that glioma progression is characterized by inflammation,
      aggressive angiogenesis, and invasion, increased levels of systemic human
      chitinase-3-like-one protein (YKL-40) have also been linked to poor prognosis.
      The aim of the present study was to assess the plausible association of YKL-40,
      NLR, and platelet count with increasing tumor grade, and evaluate their status as
      independent prognostic factors in terms of overall survival (OS) in treatment
      naive patients with diffuse glioma. Plasma levels of both biochemical markers in
      72 diffuse gliomas, median age 42 years, were compared with 36 controls.
      Comparison of YKL-40, NLR, and PC with respect to tumor grade was found to be
      significant for each of the markers (P <0.0001) while an inverse significant
      correlation was seen for YKL-40 and NLR with OS (r = -0.4619, P <0.0001, and r = 
      0.5561, P < 0.0001, respectively). NLR was the best performing marker with AUC
      0.9417 at 97% specificity. In addition, YKL-40 had a positive correlation with
      NLR (r = 0.4902, P <0.0001), indicating that expression of both markers was
      linked to inflammation and tumor progression as they were significantly
      correlated with tumor grade. Expression of YKL-40 and NLR was independently
      associated with worse survival (HR 1.0062, P = 0.039, and HR 1.1787, P = 0.0003,
      respectively), thus establishing their clinical utility as prognosticators for
      diffuse gliomas.

PMID- 30276164
TI  - Potential Use of Amniotic Membrane - Derived Scaffold for Cerebrospinal Fluid
      Applications.
AB  - Scaffolds derived from decellularized tissues provide a natural microenvironment
      for cell culture. Embryonic cerebrospinal fluid (e-CSF) contains factors which
      play vital roles in the development of the nervous system. This research was
      aimed to survey the effect of Wistar rat e-CSF on neural differentiation of bone
      marrow derived mesenchymal stem cells (BM-MSCs) cultured on the human amniotic
      membrane (AM). BM-MSCs were collected from femurs and tibias, and were cultured
      in Dulbecco's Modified Eagle's Medium. The placenta was harvested from healthy
      women during cesarean section and AM was acellularized using EDTA and physical
      scrubbing. e- CSF was harvested from rat fetuses at E17. Adequate numbers of BM
      MSCs were cultured on acellularized membrane, and were treated with E17 CSF for 7
      days. MTT (3-(4, 5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide) assay
      confirmed the survival and proliferation of BM-MSCs cultured on AM derived
      scaffold. Hematoxylin/eosin staining and scanning electron microscopy showed the
      morphological and the structural changes of BM-MSCs throughout the culture and
      treatment with e-CSF. The results of immunocytochemistry showed that microtubule
      associated protein 2 and beta-III tubulin were expressed in BM-MSCs cultured on
      acellular amnion scaffold and treated with e-CSF. Our results showed for the
      first time that the combination of acellular AM as a natural scaffold and e-CSF
      as a source of neurological factors could effectively improve the BM-MSCs
      cultivation and differentiation.

PMID- 30276167
TI  - Dysregulated Expression and Subcellular Localization of Base Excision Repair
      (BER) Pathway Enzymes in Gallbladder Cancer.
AB  - Base excision repair (BER) pathway is one of the repair systems that has an
      impact on radiotherapy and chemotherapy for cancer patients. The molecular
      pathogenesis of gallbladder cancer is not known extensively. In the present study
      we investigated whether the expression of AP endonuclease 1 (APE1) and DNA
      polymerase beta (DNA pol beta), key enzymes of BER pathway has any clinical
      significance with gallbladder carcinogenesis. 41 gallbladder cancer, 27 chronic
      cholecystitis, and 3 normal gallbladder specimens were analyzed for the
      expression of APE1 and DNA polymerase beta by western blotting, and subcellular
      localization studied by immunohistochemistry. The enzymatic activity of APE1 was
      also studied. The correlations with expression of the above proteins with
      clinical-pathological characteristics of gallbladder cancer patients were
      analyzed. The integrated density value ratio (relative expression) of total APE1
      (37 kDa + 35 kDa variant) analyzed in the three groups of tissues, was 0.76+/
      0.03 in normal gallbladder, 0.91+/-0.08 in chronic cholecystitis, and 1.12+/-0.05
      in gallbladder cancer. APE1 was found to be up-regulated in 80% of gallbladder
      carcinoma samples (P = 0.01). A positive trend of APE1 expression with tumor
      stage and lymph node positivity was observed. The enzymatic activity of APE1 was
      found higher in gallbladder cancer samples in comparison with chronic
      cholecystitis. The integrated density value ratio of DNA polymerase beta for
      normal gallbladder, chronic cholecystitis and gallbladder cancer tissue samples
      were 0.46+/-0.03, 0.7+/-0.06 and 1.33+/-0.1, respectively. DNA polymerase beta
      was found to be upregulated in almost all gallbladder carcinoma samples (P
      =0.0001), and its expression was negatively correlated with age (P=0.02). DNA
      polymerase beta expression showed a positive trend with tumor stage and nuclear
      differentiation of gallbladder cancer. It may be concluded that alteration of
      these BER pathway proteins may be the causal factors for carcinogenesis of
      gallbladder, and has targeted therapeutic potential.

PMID- 30276169
TI  - Blocking barrier and leaning hill.

PMID- 30276170
TI  - Exercise and osteoarthritis: an update.

PMID- 30276168
TI  - Screening for Non-polyenic Antifungal Produced by Actinobacteria from Moroccan
      Habitats: Assessment of Antimycin A19 Production by Streptomyces albidoflavus
      AS25.
AB  - Fungal diseases are currently a serious public health problem, due to the limited
      number of fact-based effective principles, and the emergence of resistant strains
      to the polyenic antifungals. The aim of this study was to screen, for non
      polyenic antifungals production by Actinobacteria, and to validate the screening
      program by characterizingthe produced compounds.Actinobacteria isolates were
      tested against four clinic human-pathogenic fungi isolated from Hospital Mohammed
      V Rabat, Morocco. The production of non-polyenic antifungal metabolites by active
      isolates was investigated based on the yeast cell specificity as challenging
      targets, antibacterial activity, activity against resistant Candida tropicalis R2
      and Pythium irregular (resistant to polyenes), inhibition of antifungal activity
      by the addition of exogenous ergosterol, and the UV-visible light
      spectrophotometric analysis of the active crude extracts.The antifungal compound
      produced was purified using various chromatographic techniques and the selected
      producing strain was identified using the polyphasic approach.Among 480
      Actinobacteria isolates, 55 showed antifungal activity against all tested
      clinically derived fungi. After performing the screening program, 4
      Actinobacteria that hadall the desired criteriawere selected. Using the
      polyphasic approach, the taxonomic position of the selected Streptomyces AS25,
      isolated from rhizospheric soil of Alyssum spinosum, showed that it belongs to
      Streptomyces genus with 100% partial 16S similarity with Streptomyces
      albidoflavus NBRC13010. On the basis of HPLC and mass spectrometry, the purified
      compound produced by Streptomyces AS25 was identified as a non-polyenic lactone,
      antimycin A19, which has been found for the first time to be produced by
      Streptomyces albidoflavus strain. Following the obtained results, it is important
      to note that our screening criteria for non-polyenic antifungals have been
      validated and the rhizospheric soil represents an interesting source to isolate
      Actinobacteria.

PMID- 30276171
TI  - The combined impacts of docosahexaenoic acid, endurance physical exercise, and
      prolonged fasting on brain function.
AB  - Docosahexaenoic acid (DHA), a long chain polyunsaturated fatty acid (PUFA) is
      highly enriched in the membrane phospholipids of the brain, neuronal tissue and
      retina. Accumulating evidence suggests that brain DHA is necessary for
      maintaining for optimal function of the cognition and the visual system,
      particularly the photoreceptor, the retina. Loss of brain DHA, especially during
      crucial brain development period, was highly associated with visual and cognitive
      defects. Here it would be addressed the effect of DHA on brain functions as
      assessed by spatial task performance using a first generation model which is
      similar to human nutrition case. And also, it was well known that prolonged
      fasting and energy restriction with endurance physical exercise stimulate
      cognitive function and brain function, which is caused by upregulated ketone body
      and upregulated brain-derived neurotropic factor (BDNF) responses. In the DHA
      intake or prolonged physical exercise, upregulated BDNF can activate
      mitochondrial biogenesis to elevate neuronal bioenergetics and enable synaptic
      formation. And it also can activate DNA repair in neurons. Further study on the
      mechanisms about the combine effects of supplementation of DHA and energy
      restriction on brain function is urgently needed in this area.

PMID- 30276172
TI  - Brief ideas about evidence-based recovery in team sports.
AB  - Performance in team sports is the expression of complex, dynamic, interactive,
      and multidimensional processes. It is now well-established that optimum recovery
      after practice or match is a key factor of team sport performance. During season
      and tournaments, improving recovery could offer an advantage for following
      performance. As a consequence of the professionalization of different roles in
      staffs, new particular roles have been developed within the team sports physician
      core in order to improve recovery protocols. Presently, scientific literature
      presents a big amount of methods used to enhance recovery based on the type of
      practice, time between session or competitions and equipment and/or staff
      accessible. These practices, usually used by teams are related to:
      ergonutritional, water therapy, massages techniques, stretching compression
      garments, sleep strategies and psychological implements. Besides, travel fatigue
      has been recognized by athletes and coaches as a challenging problem that could
      benefit from practical solutions. Nowadays, players have to play a lot of matches
      without enough time to recover among them, therefore the use of well-managed
      recovery can lead to a competitive advantage. Although the main purpose of
      applied sport sciences investigation is to categorize the protocols as well as
      providing approaches for individual recovery, the stages to recognize the most
      appropriate recovery plans in the field of team sports come from the analysis of
      the individual parameters.

PMID- 30276174
TI  - The effect of aerobic exercises on lipid profile of patients with human
      immunodeficiency virus infection undergoing highly active antiretroviral therapy:
      a protocol for a systematic review.
AB  - Patients living with human immunodeficiency virus (HIV) infection who are treated
      with highly active antiretroviral therapy (HAART) often experience metabolic
      changes that have an adverse effect on their over-all health status. This review
      will assess the effect of aerobic exercises on the lipid profile of individuals
      with HIV infection undergoing HAART. Cochrane Library, MEDLINE, CINAHL
      (Cumulative index to Nursing and Allied Health Literature), OVID, ProQuest, AMED
      (Allied and Complementary Medicine Database), PsycINFO, Web of Science Core
      Collection and Pedro databases will be searched until June 2018. Studies that
      investigated the effects of aerobic exercises on the lipid profile of HAART
      treated patients with HIV will be included. Two reviewers will screen all
      articles for eligibility and independently evaluate the risk of bias, complete
      quality assessment and extract data for all included articles. Homogenous
      quantitative outcome data will be analyzed using a random effect model of meta
      analysis with results presented as relative risk for dichotomous variable and
      standardized mean for continuous variable. Heterogeneous qualitative data will be
      analyzed using narrative synthesis. This systematic review will provide evidence
      about the effectiveness of aerobic exercises in managing HAART related
      dyslipidemia in patients with HIV infection and thus provide the impetus for more
      structured exercise interventions.

PMID- 30276173
TI  - Role of exercise in age-related sarcopenia.
AB  - Sarcopenia is an age-associated decline of skeletal muscle mass and function and
      is known to lead to frailty, cachexia, osteoporosis, metabolic syndromes, and
      death. Notwithstanding the increasing incidence of sarcopenia, the molecular and
      cellular mechanisms driving age-related sarcopenia are not completely understood.
      This article reviews current definitions of sarcopenia, its potential mechanisms,
      and effects of exercise on sarcopenia. The pathogenesis of age-related sarcopenia
      is multifactorial and includes myostatin, inflammatory cytokines, and
      mitochondria-derived problems. Especially, age-induced mitochondrial dysfunction
      triggers the production of reactive oxygen species (ROS) by mitochondria, impedes
      mitochondrial dynamics, interrupts mitophagy, and leads to mitochondria-mediated
      apoptosis. Aerobic exercise provides at least a partial solution to sarcopenia as
      it ameliorates mitochondria-derived problems, and resistance exercise strengthens
      muscle mass and function. Furthermore, combinations of these exercise types
      provide the benefits of both. Collectively, this review summarizes potential
      mechanisms of age-related sarcopenia and emphasizes the use of exercise as a
      therapeutic strategy, suggesting that combined exercise provides the most
      beneficial means of combating age-related sarcopenia.

PMID- 30276175
TI  - Diosgenin improves functional recovery from sciatic crushed nerve injury in rats.
AB  - Peripheral nerve injuries are commonly encountered clinical problem and often
      result in chronic pain and severe functional deficit. Diosgenin is a plant
      steroidal saponin and has anti-inflammatory and anticancer effects. In the
      present study, we investigated the effect of diosgenin on functional recovery
      following sciatic crushed nerve injury in rats. Walking track analysis for the
      functional recovery which can be quantified with the sciatic function index (SFI)
      was conducted. Immunohistochemistry for c-Fos in the ventrolateral periaqueductal
      gray (vlPAG) and paraventricular nucleus (PVN) and western blot for brain-derived
      neurotrophic factor (BDNF), tyrosine kinase B (TrkB), cyclooxygenase-2 (COX-2),
      and inducible nitric oxide synthesis (iNOS) in the sciatic nerve were performed.
      The right sciatic nerve was crushed for 30 sec using a surgical clip. The animals
      in the diosgenin-treated groups received orally once a day at the respective
      doses for 7 consecutive days, starting one day after surgery. Sciatic crushed
      nerve injury showed characteristic gait changes showing decrease of SFI value.
      Diosgenin treatment increased the SFI value and suppressed nerve injury-induced c
      Fos expression in the vlPAG and PVN. Diosgenin treatment inhibited nerve injury
      induced increase of BDNF, TrkB, COX-2, and iNOS expressions. It is possible that
      diosgenin can be used as the new therapeutic agent for pain control and
      functional recovery following peripheral nerve injury.

PMID- 30276176
TI  - High prevalence of cognitive impairment among students near mount Merapi: a case
      study.
AB  - This descriptive, cross-sectional study illustrates the high prevalence of
      intellectual impairment among students at the Kanisius Prontakan primary school
      near Mt. Merapi, one of the most active volcanic mountains in Indonesia. To
      determine the possible cause of these abnormal cognitive impairments, we
      considered and investigated the threats to society and the environment of the
      frequent volcanic eruptions, as well as the effects of malnutrition due to
      extreme poverty, in that area. The results showed that intellectual impairment
      and stunting were remarkably common among the students, with 10.7% of the
      students showing sigma of intellectual impairment and 96.4% showing signs of
      stunting. No noticeable chemical problems due to the volcanic activity were found
      in the drinking water, and no causes of such disorders other than poor nutrition
      due to poverty were found. Nevertheless, our results provide information on the
      high prevalence of health problems being experienced by children living in one of
      the most isolated and underdeveloped volcano mountain areas in Indonesia and
      draws attention to the severe effects of malnutrition on the development of those
      children.

PMID- 30276177
TI  - Effect of yoga practices on psycho-motor abilities among intellectually disabled
      children.
AB  - The children with intellectual disabilities show disorders at motor development
      and coordination. Hence, the objective of this study was to see the effect of
      yoga practices on psycho-motor abilities of intellectually disabled children.
      Seventy intellectually disabled children were divided into experimental group and
      control group. Both experimental and control group were assessed on the first day
      and after 12 weeks of the yoga intervention for static balance, eye hand
      coordination, agility and reaction time. The subjects of experimental group then
      underwent a training of yoga practices, for 1 hr for a total period of 12 weeks.
      The result of within group comparison revealed significant improvement in static
      balance, eye hand coordination, agility, and reaction time (P< 0.001) in subjects
      of yoga group however no change was observed in control group. The present study
      demonstrated that 12 weeks of yoga is effective in improving psycho-motor
      abilities of intellectually disabled children.

PMID- 30276178
TI  - The effects of whole body vibration exercise intervention on electroencephalogram
      activation and cognitive function in women with senile dementia.
AB  - This study conducted the Korean version of Mini-Mental State Examination (MMSE-K)
      to women aged 65 or older residing in Gangwon-do Province and screened those who
      were suspicious to have mild dementia for receiving 23 points or lower in it. For
      eight weeks, this author tried to verify the effects of whole body vibration
      exercise intervention on electroencephalogram (EEG) activation and cognitive
      function in women with senile dementia. According to the results, both EEG
      activation and cognitive function indicated statistically significant difference
      in terms of the interactive effect between the measuring times and groups, and
      there was statistically significant improvement found after the whole body
      vibration exercise intervention. The results of this study are meaningful because
      they present the possibility of whole body vibration exercise intervention to be
      integrated into the plan to improve life quality in patients with senile dementia
      by stimulating their muscle spindles and sensory organs only with the amplitude
      and the number of vibrations with no burden of physical activity and enhancing
      their EEG activation and cognitive function through the responses of the
      neuromuscular system.

PMID- 30276179
TI  - Analysis of the relationship between physical activity and metabolic syndrome
      risk factors in adults with intellectual disabilities.
AB  - The purpose of this study was to investigate the relationship between physical
      activities and metabolic syndrome risk factors in adults with intellectual
      disabilities. Seventeen adults with intellectual disabilities at a sheltered
      workshop wore Actical for 5 days on workdays to measure their physical activity,
      and blood samples were taken to measure their physical fitness factors and
      examine their risk factors for metabolic syndrome. The average daily physical
      activity was found to be 655.41+/- 129.36 kcal, and the average total physical
      activity over 5 days was 3,224.94+/-149.68 kcal. A positive correlation was
      confirmed between physical activity and muscular strength, muscular endurance,
      total cholesterol, low-density lipoprotein cholesterol and disability rating.
      Factors that predicted physical activity of adults with disabilities were
      disability rating (t=6.280, P<0.001) and glycated hemoglobin (t= -2.315,
      P<0.036), which had a 73.9% correlation (R 2=0.739) with the physical activities
      of adults with intellectual disabilities. In conclusion, the physical activity
      level of adults with intellectual disabilities was significantly lower than that
      of adults in similar age groups, and such low physical activity may affect their
      muscular strength, muscular endurance, and metabolic syndrome risk factors.
      Therefore, additional studies on programs to improve and enhance physical
      activities at sheltered workshops, where adults with intellectual disabilities
      are mainly supervised and active, and guidelines for continuous health management
      are needed.

PMID- 30276180
TI  - The relationship between children's flourishing and being overweight.
AB  - This study examined the effect of children's flourishing on the pandemic of
      obesity from various aspects such as age, gender, race, family, school, and
      community. By using a subsample of the 2011-2012 National Survey of Children's
      Health, the Flourishing scale analyses were performed with a total of 45,309
      children. Childhood obesity was diagnosed by calculating the percentile of the
      body mass index. Hispanic Americans were more likely to be overweight (P<0.01).
      Nonoverweight children were more likely to participate in after-school
      activities, less likely to have sedentary behavior, more likely to miss school,
      to be more active, and had more of flourishing than their counterpart (P<0.01).
      Parent's marital and health status also positively affect children's obesity
      status (P<0.01). Social capital and neighbor amenities significantly affect
      children's weight status (P<0.01). A multifaceted understanding of the role of
      family, school, and community (with proving children's flourishing environment)
      in terms of how and what could contribute to children's obesity status is
      important in order to bring about positive impact.

PMID- 30276181
TI  - Factors that influence hospital inpatients' exercise constraints.
AB  - The purpose of this study is to present ways to provide more precise patient
      oriented services by presenting implications and promoting a better understanding
      of exercise constraints. This study used questionnaire survey as measurement tool
      for 196 hospital inpatients in 5 general hospitals in the metropolitan area
      (Seoul, Gyeonggi, and Incheon). The collected data were analyzed using frequency
      analysis, exploratory factor analysis, reliability analysis, correlation
      analysis, and hierarchical regression analysis using IBM SPSS Statistics ver.
      23.0. The following results were obtained. First, physical activity level and
      health condition on their physical constraints showed that their health condition
      factors such as pain/discomfort and anxiety/depression had greater effects on
      physical constraints than other factors. Second, physical activity level, and
      health condition on their psychological constraints showed that health condition
      factors had major effects on patients' psychological constraints. Thirdly,
      physical activity level, and health condition on their sociocultural constraints
      found that anxiety/depression appeared as the key influence factor in physical
      and psychological constraints.

PMID- 30276182
TI  - Training methods and analysis of races of a top level Paralympic swimming
      athlete.
AB  - Training methods for Paralympic swimmers must take into account different
      pathologies, competitions classes, athlete's individual circumstances and
      peculiar physical adaptation mechanisms, hence general guidelines cannot be found
      in literature. In this study we present a training program, implemented for the
      physical preparation of a top level Paralympic swimmer. The athlete under study,
      affected by infantile cerebral palsy within a clinical picture of a spastic
      tetraparesis, by the end of 2016 was holder of Italian, European, world and
      Paralympic titles in the 400-m freestyle competition, S6 class. The training
      macrocycle was structured in a 3-fold periodization (three mesocycles), in view
      of the preparation to three international competitions. The 4-month training
      mesocycles prior to each competition differed substantially in terms of mileage
      load, intensity and recovery times. The first mesocycle was characterized by a
      sizeable low-intensity mileage load, the second one was shifted to lower mileage
      load, carried out at middle-to-high intensity levels, the third one entailed
      increased effort intensity, counterbalanced by lower mileage load. In all cases,
      recovery times were balanced to obtain optimized performance through physical
      adaptation to training stimuli, keeping into account the physiopatological
      response. Tapering phases were adjusted to maximize performance at competition.
      As an assessment of the effectiveness of the training method, correspondence
      between chronometric and technical parameters in the three competitions and the
      respective mesocycle training programs was found. The results of the present
      study may support the development of training guidelines for athletes affected by
      upper motor neuron lesions.

PMID- 30276183
TI  - The reproducibility and validity verification for body composition measuring
      devices using bioelectrical impedance analysis in Korean adults.
AB  - The purpose of this study is to examine the validity and reproducibility of
      impedance body fat measurement devices measuring the body composition of Korean
      male and female adults using three bioelectrical impedance analyzers. We compared
      two methods for evaluating body composition: dual energy X-ray absorptiometry
      (DEXA), and bioelectrical impedance analysis (BIA). Subjects were 200 healthy
      adult Korean males and females whose mean+/-standard deviation (range) age,
      standing height, body weight, and body mass index (BMI) were 44.1+/-14.5 years,
      172.8+/-7.4 cm, 76.0+/-12.8 kg, and 25.4+/-3.3 kg/m2, and 44.5+/-14.7 years,
      158.7+/-5.8 cm, 58.3+/-8.3 kg, and 23.2+/-3.0 kg/m2, respectively. As a result,
      first of all, the reproducibility of the bioelectrical impedance analyzer had
      very high coefficients at r=0.998, r=0.997 between men and women, respectively.
      The correlation coefficients among three comparisons for lean body mass (LBM)
      were provided the following coefficients: r=0.951 for DEXA vs. ACCUNIQ BC720,
      r=0.950 for DEXA vs. ACCUNIQ BC360, and r=0.946 for DEXA vs. ACCUNIQ BC380 in
      men. In the results for women, they also had the very high following
      coefficients: r=0.956 for DEXA vs. ACCUNIQ BC720, r=0.946 for DEXA vs. ACCUNIQ
      BC360, and r=0.957 for DEXA vs. ACCUNIQ BC380 in LBM. In conclusion, this
      research showed a higher correlation in terms of accuracy compared to existing
      BIA-based body composition measurement techniques, and the accuracy of LBM was
      improved with high correlation coefficients through the algorithm that was
      improved using the multifrequency BIA method in the ACCUNIQ BC products.

PMID- 30276184
TI  - Comparison of lumbar multifidus thickness and perceived exertion during graded
      superman exercises with or without an abdominal drawing-in maneuver in young
      adults.
AB  - The present study aimed to investigate lumbar multifidus (LM) thickness and
      perceived exertion during graded superman exercises (GSE) or GSE with an
      abdominal drawing-in maneuver (GSE-AD) in young adults. Twelve young adult males
      and females, who were informed of the purpose and procedures of this study and
      then gave their voluntary consent to participate, were included in this study.
      All subjects randomly performed three GSE and GSE-AD over 3 days. Ultrasonography
      was used to measure the LM thickness to the left and right of the L5 region.
      Additionally, the issue of whole-body fatigue felt by the subject while
      performing the GSE or GSE-AD was measured using the Borg scale. The intrarater
      reliability of the LM measurement was found to be intraclass correlation
      coefficient (ICC[3,1])=0.97 (0.87-0.99) at resting and ICC(3,1)=0.94 (0.78-0.99)
      at contraction. Both the left and right LM showed significantly higher
      contraction during the grade 3 GSE (P< 0.05). The whole-body fatigue was
      significantly greater following GSE 2 and 3 than following GSE-AD 2 and 3
      (P<0.05). In particular, GSE-AD had a significantly lower Borg score compared to
      GSE (P<0.05) and did not show any significant difference in muscle thickness
      (P>0.05). It is recommended that the abdominal drawing-in maneuver be applied
      with grade 3 GSE to enhance stability and reduce spinal fatigue.

PMID- 30276185
TI  - Evaluation of nocturnal heart rate variability for strenuous exercise day using
      wearable photoelectric pulse wave sensor.
AB  - In this study, we examined whether or not the strenuous exercise in the evening
      change nocturnal heart rate variability (HRV) and recovers. Subjects were 8
      healthy men belonging to the mature futsal team (age: 35+/-3 years) and Futsal
      was held from 5:00 p.m. to 6:30 p.m. on Sunday. Pulse waves during sleeping were
      measured at home on exercise day and on control day. The mean pulse interval
      (MPI), standard deviation pulse interval (SDPI), low frequency component (LF,
      0.04-0.15 Hz), high frequency component (HF, 0.15-0.45 Hz) and the ratio of LF to
      HF (LF/HF) were calculated from pulse interval time series every 30 min. As a
      result, MPI, SDPI, LF, HF of exercise day were significantly lower than control
      day (P<0.0001). LF/HF of exercise day was significantly higher than control day
      (P<0.05). Regarding change of HRV for every 30 min, MPI (P<0.05), SDPI
      (P=0.0003), LF (P=0.0038), HF (P<0.05) were observed significant changes. MPI and
      HF before wake-up did not reach the level of control day. It is thought that
      strenuous exercise in the evening promotes sympathetic nervous activity during
      night sleep and suggesting that pulse rate and HRV have not recovered by the wake
      up time.

PMID- 30276186
TI  - The influence of ovulation on postural stability (Biodex Balance System) in young
      female.
AB  - The purpose of this study was to examine the influence of ovulation (OV) on
      dynamic balance in young female. Thirty-two eumenorrheic healthy women
      participated in Biodex Balance System (BBS) test for postural stability and a
      limit of stability menstrual cycle. BBS was tested in the menses (MS), OV, and
      luteal phase (LP). The limits of stabilities (total, forward-left, forward-right,
      backward-left, and backward-right) were significantly higher in the OV (total,
      61.44+/-14.77; forward-left, 67.50+/- 15.17; forward-right, 69.50+/-14.43;
      backward-left, 64.00+/-20.32; and back-ward-right, 69.06+/-13.59) than in the MS
      (total, 55.44+/-14.63; forward-left, 60.00+/-15.98; forward-right, 62.17+/-9.78;
      backward-left, 57.83+/-19.09; and backward-right, 57.28+/-13.73). Furthermore,
      the LP (65.11+/-13.79) was a significantly higher limit of stability than MS
      (57.28+/-13.73) during back-ward-right. The present study showed that estrogen
      negatively influences postural stability. The postural sway in limits of
      stabilities (total, forward-left, forward-right, backward-left, and backward
      right) were significantly the greatest in the OV. Since there is a different
      postural stability between MS, OV, and LP, this should be taken into account when
      devising training programs to avoid risk factor of fall and joint injury.

PMID- 30276187
TI  - Incidence analysis of axial and lower extremity deviations based on the physical
      characteristics between domestic and foreign college students.
AB  - This research was performed to identify the incidence and to determine the
      effects of risk factors of axial and lower extremity deformities. One hundred
      forty-seven domestic college students (102 males and 45 females) and 72 foreign
      students (33 males and 39 females) were subjects in this study. Data collecting
      was performed by questionnaire and visual postural evaluation. For backpack
      shoulder dominance, higher incidences of genu varus (P=0.043) and lower incidence
      of leg length discrepancy (LLD) (P=0.001) were found in both shoulder carrier,
      while the incidence of lordosis was higher in left (P=0.001) and both (P=0.012)
      carrier in domestic students. The incidence of genu varus (P=0.022) and scoliosis
      (P=0.002) were significantly lower in both shoulder carrier in foreign students.
      For dominant arm, the incidence of forward head (P=0.001) and of lordosis
      (P=0.029) were significantly higher in left handedness both in domestic students
      and in foreign students. As the body mass index increases, the incidence of
      protruding abdomen (P=0.001) and lordosis (P=0.009) showed significant increase,
      but, the incidence of kyphosis (P=0.022) and scoliosis (P=0.001) decreased in
      domestic students, and same tendency for lordosis (P=0.001) and for scoliosis
      (P=0.001) in foreign students. As a whole, in domestic students, female students
      revealed significantly high (P=0.004) incidence of genu recurvatum compared to
      significantly low (P=0.022) incidence of LLD. However, no significant incidence
      difference found in foreign students. Male students showed significantly low
      incidence (P=0.001) of LLD and high incidence (P=0.014) of lordosis. In foreign
      students, female students also showed significantly low incidence (P=0.032) of
      LLD in foreign students compared to their counterparts.

PMID- 30276188
TI  - Effects of diaphragm and deep abdominal muscle exercise on walking and balance
      ability in patients with hemiplegia due to stroke.
AB  - The aim of this study was to investigate the effects of diaphragm and deep
      abdominal muscle exercise (DDAME) on walking ability (WA) and balance ability
      (BA) in subjects with hemiplegia due to stroke. Study subjects consisted of
      twenty patients diagnosed with hemiplegia due to stroke. They were randomized
      into a control group (CG) (n=10) that performed traditional exercise and an
      experimental group (EG) (n=10) that performed DDAME. The WA was measured using
      the 10-m walking test (10MWT) and 6-min walk test (6MWT). The BA was measured
      using the Timed Up and Go test (TUG) and Berg's balance scale (BBS). Paired t
      test was performed to compare differences within the groups before and after
      intervention. The analysis of covariance was performed to compare the differences
      between the EG and CG. The level of significance was set at alpha=0.05. Within
      group changes in 10MWT and 6MWT were significantly different in both the EG
      (P<0.05) and CG (P<0.05). There was significantly more improvement in the 10MWT
      and 6MWT in the EG than in the CG (P<0.05). Within-group changes in TUG and BBS
      were significantly different in both the EG (P<0.05) and the CG (P<0.05). There
      was significantly more improvement in TUG and BBS in the EG than in the CG
      (P<0.05). DDAME program, with diaphragm and inspiratory muscle strengthening
      exercises, is needed for patients experiencing difficulty in WA, BA, trunk
      asymmetry, abnormal alignment, mobility of trunk muscles, power, or endurance
      decline.

PMID- 30276189
TI  - Functional resistance training can increase strength, knee torque ratio, and
      functional performance in elderly women.
AB  - Functional resistance training can increase strength, knee torque ratio, and
      functional performance in elderly women. The aim of the present study was to
      understand the effects of closed kinetic chain exercises with constant load on
      muscular strength, the knee torque conventional ratio (hamstring:quadriceps -
      H:Q), and functional capacity in the elderly. Nine untrained healthy elderly
      women participated in experimental resistance training. Ten-repetition maximum
      (10RM) for the deadlift, isokinetic maximum voluntary concentric contraction, and
      functional capacity were assessed before and after the 7-week resistance-training
      program. Magnitude based inference analysis was used to examine the differences
      in muscle strength and functional performance. Therefore, the smallest worthwhile
      change was calculated and 90% confidence intervals were also determined to
      characterize muscle strength and functional performance. The analysis
      demonstrated an increase in the deadlift and knee flexor torque (60o/sec) after
      the experimental intervention. Furthermore, stair ascent, knee extensor torque
      (120o/sec), knee flexor torque (120o/sec), and knee ratio (60o/sec) also
      presented a positive effect in the same training period. Conversely, knee
      extensor torque (60o/sec), and knee ratio (120o/sec) did not show conclusive
      responses. In conclusion, resistance training with functional closed kinetic
      chain exercises and constant volume load (i.e., 65% of 1-repetition maximum) can
      increase deadlift 10RM, isokinetic concentric torque, the conventional H:Q ratio,
      and stair ascent performance in elderly women.

PMID- 30276190
TI  - The effects of combined aerobic and resistance training on inflammatory markers
      in obese men.
AB  - It is important to treat obesity and the related noncommunicable diseases. The
      main objective of this study is the effect of different training types on
      inflammatory and immune markers in obesity. Seventeen obese men with body mass
      index (BMI)>=26 kg/m2 were randomly divided into two groups: aerobic training
      group (AT; n=9) and combined aerobic and resistance training group (CT; n=8).
      Body composition (weight, BMI, %body fat), factors of physical performance (one
      repetition maximum [1RM], maximal oxygen uptake [VO2max]), inflammatory markers
      (interleukin-6, tumor necrosis factor-alpha [TNF-alpha]), immune markers
      (leukocyte, natural killer cell) were analyzed before and after 8-week training.
      Body composition (weight, BMI, and %body fat) was significantly reduced after
      training in both the AT and CT groups (P<0.05). As a result of training, VO2max
      of all training groups was increased and 1RM of CT group was partially improved.
      In particular, the inflammatory marker, TNF-alpha was significantly reduced
      (P<0.05) and the change was correlated with %body fat in the posttraining CT
      group. In this study, we found that combined training for 8 weeks improved
      physical fitness, body composition, and inflammation. It is suggested that
      restoring obesity through combined training of aerobic and resistance exercise is
      related to changes in serum TNF-alpha levels.

PMID- 30276191
TI  - The effects of circuit training on the indexes of sarcopenia and the risk factors
      of metabolic syndrome in aged obese women.
AB  - The purpose of this study is to examine the effects of circuit training on the
      indexes of sarcopenia and the risk factors of metabolic syndrome in aged obese
      women. To address the goal, this author selected aged women whose body mass index
      was higher than 25.0 kg/m2 visiting the welfare center for the aged located in
      Gangwon-do Province and measured the indexes of sarcopenia and the risk factors
      of metabolic syndrome after circuit training. Through that, this study has gained
      following results. First, after circuit training, aged obese women's indexes of
      sarcopenia indicated statistically significant difference in terms of interaction
      between the measuring times and groups. Second, after circuit training, aged
      obese women's risk factors of metabolic syndrome (systolic blood pressure,
      diastolic blood pressure, fasting blood sugar, triglycerides, high-density
      lipoprotein-cholesterol, and waist circumference) showed statistically
      significant difference in terms of interaction between the measuring times and
      groups. To sum up the above results, circuit training improves aged obese women's
      indexes of sarcopenia and risk factors of metabolic syndrome positively, which
      means circuit training is found to be effective. Therefore, the circuit training
      intervention enhances aged obese women's muscular and metabolic functions
      positively. As it helps prevent and manage the risk factors of sarcopenia and
      metabolic syndrome resulted from aging, it will elevate life quality in
      senescence.

PMID- 30276192
TI  - Oral adenosine 5'-triphosphate supplementation improved hemodynamic and autonomic
      parameters after exercise in hypertensive women.
AB  - The aim of this study was to verify the autonomic modulation and blood pressure
      after adenosine-5'-triphosphate (ATP) supplementation associated to acute aerobic
      exercise in hypertensive women. Eleven hypertensive women (age, 61.8+/-5.0 years)
      completed a randomized, double blind trial: ATP supplement condition (ATP=400 mg)
      or placebo. After 30 min of supplementation or placebo intake, the subjects
      performed 30 min of aerobic exercise (70%-75% of maximum heart rate). The
      autonomic modulation was assessed by heart rate variability during rest and
      recovery (postexercise until 30 min of recovery), the square root of the mean
      squared difference between adjacent RR intervals (RMSSD), standard deviation of
      successive values (SDNN), low frequency (LF) and high frequency (HF) were
      measured. The blood pressure (systolic blood pressure [SBP] and diastolic blood
      pressure, mmHg) were recorded at rest, immediately postexercise, post-10, post
      20, and post-30 min after exercise. For RMSSD, there was statistically
      significant difference during recovery, with higher RMSSD for ATP compared to
      placebo (rest=16.4+/-8.5 vs. placebo=11.6+/-4.0; ATP=18.5+/-9.7 msec; P=0.020).
      When analyzing the delta (recovery minus rest), the RMSSD (ATP=2.1+/- 7.2 msec
      vs. placebo=-4.7+/-7.5 msec; P=0.009), LF (ATP=-19.8+/-122.7 vs. placebo=-94.1+/
      200.2 msec2; P=0.02), and SDNN (ATP=-2.8+/-12.2 msec vs. placebo=-10.6+/-10.5
      msec; P=0.010) were higher for ATP than placebo. Furthermore, there was a greater
      postexercise hypotension at 20 min for ATP (SBP: ATP=-13.2+/-8.4 mmHg vs.
      placebo=-6.1+/-9.9 mmHg; P=0.006). Acute ATP supplementation promoted greater
      postexercise hypotension for systolic blood pressure and induced faster recovery
      of heart rate variability in hypertensive women.

PMID- 30276193
TI  - Functional capacity and ventilatory efficiency are preserved in well-controlled
      people living with human immunodeficiency virus/acquired immunodeficiency
      syndrome.
AB  - To verify and compare the responses of the cardiopulmonary variables to the
      incremental test in physically inactive people living with human immunodeficiency
      virus (HIV)/acquired immune deficiency syndrome (AIDS) (PLWHA) with well
      controlled disease and physically inactive healthy subjects (non-HIV/AIDS).
      Participants performed a cardiopulmonary exercise test (CPX) on a treadmill. Data
      were analyzed using the Mann-Whitney test and Spearman correlation. Nine PLWHA (5
      women) and 9 non-HIV/AIDS gender and activity level-matched controls were
      included in the data analysis. Data are expressed in median (range). No
      difference was shown in the PLWHA group when compared to the control group in
      functional capacity (peak oxygen consumption [VO2peak]: 29.9 (20.9-36.4)
      mL/kg/min vs. 32.2 (24.5-39.4) mL/kg/min) and ventilatory efficiency (oxygen
      uptake efficiency slope [OUES]: 2,058 [1,474-3,204] vs. 2,612 [1,383-4,119];
      minute ventilation carbon dioxide production slope: 27.4 [22.5-33.6] vs. 27.5
      [20.4-38.1]). The results are also similar to maximal heart rate, oxygen pulse,
      gas exchange threshold, respiratory compensation point, heart rate recovery, and
      half-time of VO2peak recovery. OUES had a strong correlation with VO2peak in the
      PLWHA group (r s =0.70, P=0.04) and control group (r s =0.78, P=0.02). The
      results of this study indicate that functional capacity and ventilatory
      efficiency in PLWHA with well-controlled disease are preserved and are not
      different from sedentary subjects. In this sense, when CPX is unavailable, the
      aerobic assessment and prescription could be based on simpler procedures used in
      healthy subjects.

PMID- 30276194
TI  - Blood pressure responses after resistance exercise session in women living with
      human immunodeficiency virus/acquired immunodeficiency syndrome.
AB  - The aim of this study was to verify blood pressure (BP) responses after a single
      resistance exercise session in women with human immunodeficiency virus/acquired
      immunodeficiency syndrome (HIV/AIDS). Twelve patients underwent a resisted
      exercise session. BP, heart rate, and rate pressure product were evaluated before
      and during 120 min after the session. Mean cardiovascular values before and after
      the session were similar (P>0.05). Analysis of the individual data revealed that
      for 120 min after exercise, 5 and 4 patients presented a reduction in systolic
      and diastolic BP of >=4 mmHg, respectively. The clinical characteristics of the
      patients appear to influence BP responses after exercise. Individual data showed
      that some of the HIV+ women demonstrated a clinically significant decrease in BP.
      Although a single resistance exercise session does not decrease BP in women with
      HIV/AIDS, individual data present heterogeneity and individual characteristics
      seem to influence BP reduction after a single session of resistance exercises.

PMID- 30276195
TI  - Duration of wrist immobilization is associated with shoulder pain in patients
      with after wrist immobilization: an observational study.
AB  - The main goal of this study was to determinate the extent of the relationship
      between shoulder pain and time of wrist and thumb immobilization required after
      injury. One hundred twenty-three consecutive subjects presenting to the practice
      of different Orthopedic Specialist hospitals with a diagnosis of distal radius or
      scaphoid fracture that required wrist and thumb immobilization were screened for
      eligibility criteria. Upper extremity pain and the need for shoulder
      rehabilitation were assessed using the visual analogue scale (VAS) at baseline
      after immobilization period (T0) 1- and 3-month follow-up (1-FU/2-FU). More than
      35% patients had shoulder pain (VAS>40 mm) after immobilization of the wrist.
      Shoulder pain intensity after immobilization and at follow-up (1 and 3 months)
      was strongly correlated with the duration of the immobilization. Immobilization
      for 3.5 weeks or longer was the strongest predictor for the need of subsequent
      shoulder rehabilitation. An increased the time of immobilization of the wrist is
      associated with an increase in shoulder pain and need for shoulder rehabilitation
      in patients after wrist fracture.

PMID- 30276196
TI  - Effect of slipper wearing and carrying positions of infant on dynamic stability
      and kinetic variable during level walking.
AB  - Recently though various hip seats for carrying infant of women was designed and
      developed, then, wearing slipper may restrain the movement of bare foot. The
      study was undertaken to investigate the dynamic stability and kinetic variables
      according to between position of carrying infant and wearing slipper. Adult
      female (n=10) and under one year age of infant (n=10) participated in the study.
      Extrapolated center of mass, center of pressure, ground reaction force (GRF), and
      leg stiffness of gait characteristics using 3-dimensional cinematography and GRF
      were analyzed. Dynamic stability according to position of carrying infant and
      wearing slipper was not significant. While when carried an infant against normal
      gait showed significant difference in breaking force, leg stiffness and loading
      rate (P<0.001). Of which breaking force and vertical impulse were more increased
      when the back-carried against fore-carried of trunk. Thus it resulted in
      transformation on types of impulse transfer to leg and COG of women's carrying
      infant, which may be strategy for securing a dynamic stability. Therefore experts
      related with exercise rehabilitation should understand sufficiently on gait
      characteristics of women with diseases on muscular-skeletal system and perform
      effective rehabilitation and treatment.

PMID- 30276197
TI  - The Effectiveness of Antiviral Treatments for Patients with HBeAg-Positive
      Chronic Hepatitis B: A Bayesian Network Analysis.
AB  - This network analysis is to determine the most effective treatment in HBeAg
      positive patients. PubMed databases were searched for randomized controlled
      trials. Bayesian network meta-analysis was used to calculate the pairwise hazard
      ratios, 95% credible intervals, and ranking of surrogate outcomes. 9 studies were
      identified. The results show that NA add-on PEG IFN might be a better antiviral
      approach for HBeAg-positive patients in end point of treatment, with a comparable
      results of nucleoside/nucleotide analogs (NA), PEG IFN, PEG IFN add-on NA, PEG
      IFN combined NA, and PEG IFN combined placebo in alanine aminotransferase (ALT)
      normalization and HBV DNA undetectable. Cumulative probabilities of being the
      most efficacious treatment were NA add-on PEG IFN (30%) for HBeAg loss. The
      second efficacious (23%) is HBeAg seroconversion. This network analysis shows
      that NA add-on PEG IFN might be a better antiviral approach for HBeAg-positive
      patients in end point of treatment. But the long-term efficiency should be
      further determined.

PMID- 30276198
TI  - Green Light-Emitting Devices Based on Perovskite CsPbBr3 Quantum Dots.
AB  - In this paper, high quality green-emitting CsPbBr3 quantum dots (QDs) are
      successfully synthesized by hot-injection method. Different injection
      temperatures are tested to optimize the synthesis conditions. High brightness
      with the photoluminescence (PL) quantum yields (QYs) up to 90% and narrow size
      distribution with the full width at half-maximum (FWHM) of 18.5 nm are obtained
      under the optimized conditions. Green light emitting diodes (LEDs) based on the
      CsPbBr3 QDs are successfully demonstrated by combining solution method with vapor
      deposition method. Composite films of poly[9,9-dioctylfluorene-co- N-[4-(3
      methylpropyl)]-diphenylamine] (TFB) and bathocuproine (BCP) layers are chosen as
      the hole-transporting and the electron-transporting layers, respectively. The
      highly bright green QD-based light-emitting devices (QLEDs) showing maximum
      luminance up to 46,000 cd/m2 with a low turn on voltage of 2.3 V, and peak
      external quantum efficiency (EQE) of 5.7%, corresponding to 19.9 cd/A in
      luminance efficiency. These devices also show high color purity for
      electroluminescence (EL) with FWHM <20 nm, and no redshift and broadening with
      increasing voltage as well as a spectral match between PL and EL.

PMID- 30276199
TI  - Medial Hypoxia and Adventitial Vasa Vasorum Remodeling in Human Ascending Aortic
      Aneurysm.
AB  - Human ascending aortic aneurysms characteristically exhibit cystic medial
      degeneration of the aortic wall encompassing elastin degeneration, proteoglycan
      accumulation and smooth muscle cell loss. Most studies have focused on the aortic
      media and there is a limited understanding of the importance of the adventitial
      layer in the setting of human aneurysmal disease. We recently demonstrated that
      the adventitial ECM contains key angiogenic factors that are downregulated in
      aneurysmal aortic specimens. In this study, we investigated the adventitial
      microvascular network (vasa vasorum) of aneurysmal aortic specimens of different
      etiology and hypothesized that the vasa vasorum is disrupted in patients with
      ascending aortic aneurysm. Morphometric analyses of hematoxylin and eosin-stained
      human aortic cross-sections revealed evidence of vasa vasorum remodeling in
      aneurysmal specimens, including reduced density of vessels, increased lumen area
      and thickening of smooth muscle actin-positive layers. These alterations were
      inconsistently observed in specimens of bicuspid aortic valve (BAV)-associated
      aortopathy, while vasa vasorum remodeling was typically observed in aneurysms
      arising in patients with the morphologically normal tricuspid aortic valve (TAV).
      Gene expression of hypoxia-inducible factor 1alpha and its downstream targets,
      metallothionein 1A and the pro-angiogenic factor vascular endothelial growth
      factor, were down-regulated in the adventitia of aneurysmal specimens when
      compared with non-aneurysmal specimens, while the level of the anti-angiogenic
      factor thrombospondin-1 was elevated. Immunodetection of glucose transporter 1
      (GLUT1), a marker of chronic tissue hypoxia, was minimal in non-aneurysmal medial
      specimens, and locally accumulated within regions of elastin degeneration,
      particularly in TAV-associated aneurysms. Quantification of GLUT1 revealed
      elevated levels in the aortic media of TAV-associated aneurysms when compared to
      non-aneurysmal counterparts. We detected evidence of chronic inflammation as
      infiltration of lymphoplasmacytic cells in aneurysmal specimens, with a higher
      prevalence of lymphoplasmacytic infiltrates in aneurysmal specimens from patients
      with TAV compared to that of patients with BAV. These data highlight differences
      in vasa vasorum remodeling and associated medial chronic hypoxia markers between
      aneurysms of different etiology. These aberrations could contribute to
      malnourishment of the aortic media and could conceivably participate in the
      pathogenesis of thoracic aortic aneurysm.

PMID- 30276201
TI  - Effect of Fungal Solid-State Fermented Product in Broiler Chicken Nutrition on
      Quality and Safety of Produced Breast Meat.
AB  - The aim of this work was to analyse the effect of addition of 10% (w/w) fermented
      bioproduct into commercial broiler feed on fatty acid profile, lipid oxidative
      stability, and sensory properties of chicken breast meat. The fermented
      bioproduct was prepared by fermentation of cornmeal by filamentous fungi
      Umbelopsis isabellina CCF 2412 in solid-state fermentation (SSF) process and the
      final bioproduct was enriched with gamma-linolenic acid and beta-carotene. In the
      experiment, 80 pieces of 1-day-old chickens COBB 500 were used. Half of them
      (control group) were fed only with commercial feed. Chickens of the experimental
      group were fed with commercial feed, and, from the 11th day of age until the time
      of slaughter (39th day), 10% of commercial feed was replaced with fermented
      bioproduct. Application of fermented bioproduct into commercial feed mixture
      positively influenced profile of fatty acids in breast meat. The amount of gamma
      linolenic, alpha-linolenic, and oleic acids in fat of breast muscles was
      increased and n-6/n-3 ratio was significantly decreased. Profile and content of
      PUFAs did not change after thermal treatment of meat. Oxidative stability of fat
      and sensory properties of the meat during the storage (4 degrees C, 7 days) of
      meat were not affected by fermented bioproduct.

PMID- 30276203
TI  - Microarray-Based Detection and Clinical Evaluation for Helicobacter pylori
      Resistance to Clarithromycin or Levofloxacin and the Genotype of CYP2C19 in 1083
      Patients.
AB  - Background. Helicobacter pylori (H. pylori) is one of the most frequent and
      persistent bacterial infections that affect nearly half of the world's
      population. Antibiotic resistance is a constantly evolving process and local
      surveillance of antibiotic resistance is warranted to guide clinicians in their
      choice of therapy. The aim of this study was to establish a microarray-based
      detection to identify H. pylori infection, clarithromycin and levofloxacin
      susceptibility, and CYP2C19 genetic polymorphism and guide to potential choice of
      proton pump inhibitor (PPI), antibiotic administration for tailored H. pylori
      eradication therapy. Methods. By analyzing the sequence of human genomic
      CYP2C19*2 and CYP2C19*3 and mutations within the 23S rRNA and gyrA gene regions
      conferring clarithromycin and levofloxacin resistance, respectively, we developed
      a microarray for individual therapy detection of H. pylori infection. Plasmids
      were established as positive or limit of detection (LOD) reference materials. The
      specificity and sensitivity of the microarray had been performed. And a total of
      1083 gastric biopsy samples were tested and the Kappa value had been calculated
      between the array and Sanger sequencing. We also analyzed the resistance to
      clarithromycin and levofloxacin in China, as well as the CYP2C19 polymorphisms.
      Results. The LOD of detecting H. pylori was 103 CFU/mL and human genome DNA was 2
      ng/MUL. The detection results of 1083 gastric biopsy samples showed that 691
      (63.80%) were H. pylori positive, of which 266 (38.49%) were resistant to
      clarithromycin, 192 (27.79%) were resistant to levofloxacin, and 61 (8.83%) were
      resistant to both of them. For the type of CYP2C19 polymorphism, 412 (38.04%)
      were homozygous fast type (HomEM), 574 (53%) were heterozygous EM (HetEM), and 97
      (8.96%) were poor metabolizer (PM). Conclusions. The proposed microarray-based
      detection has high specificity, sensitivity, and reproducibility for detecting
      the resistance of clarithromycin or levofloxacin as well as CYP2C19 polymorphism,
      which may help to improve the clinical eradication rate of H. pylori.

PMID- 30276204
TI  - Biochemical Changes and Biological Origin of Key Odor Compound Generations in Pig
      Slurry during Indoor Storage Periods: A Pyrosequencing Approach.
AB  - Production of odors is a complex process. Many bacterial species are involved in
      the production of an extensive array of key odor compounds in stored pig slurry.
      Understanding of basic microbial communities and their role during storage
      periods is an essential way to control and prevent the odors generations. In this
      aspect, the pig slurry samples were taken directly from deep pits of finisher pig
      building every two weeks, their biochemical changes were analysed, and the
      indigenous bacterial communities that involve in offensive odor producing
      compounds were identified. The SCFA, BCFA, phenols, and indoles levels altered
      drastically in the slurry during storage periods. The COD, BOD, SS, P2O5, TKN,
      and NH4-N were increased in the stored slurry. Bacterial ecology indicates
      Firmicutes and Bacteroidetes phyla were dominantly found in pig slurry. Odorants
      produced in pig slurry were correlated with bacterial communities. Phenols,
      indoles, SCFA, and BCFA productions were positively correlated with bacteria
      species which comes under phyla of Firmicutes and Bacteroidetes. It seems that
      bacterial species under Firmicutes and Bacteroidetes phyla play an important role
      in the offensive odor compounds production. Taken together, the prevention of
      these phyla bacterial growth and early discharge of pig slurry might reduce the
      offensive odor production.

PMID- 30276202
TI  - Fractional Flow Reserve Derived from Coronary Computed Tomography Angiography
      Datasets: The Next Frontier in Noninvasive Assessment of Coronary Artery Disease.
AB  - Fractional flow reserve (FFR) derived from coronary CTA datasets (FFRCT) is a
      major advance in cardiovascular imaging that provides critical information to the
      Heart Team without exposing the patient to excessive risk. Previously, invasive
      FFR measurements obtained during a cardiac catheterization have been demonstrated
      to reduce contrast use, number of stents, and cost of care and improve outcomes.
      However, there are barriers to routine use of FFR in the cardiac catheterization
      suite. FFRCT values are obtained using resting 3D coronary CTA images using
      computational fluid dynamics. Several multicenter clinical trials have
      demonstrated the diagnostic superiority of FFRCT over traditional coronary CTA
      for the diagnosis of functionally significant coronary artery disease. This
      review provides a background of FFR, technical aspects of FFRCT, clinical
      applications and interpretation of FFRCT values, clinical trial data, and future
      directions of the technology.

PMID- 30276205
TI  - Application of 3D-Printed Personalized Guide in Arthroscopic Ankle Arthrodesis.
AB  - Objective: To accurately drill the Kirschner wire with the help of the 3D-printed
      personalized guide and to evaluate the feasibility of the 3D technology as well
      as the outcome of the surgery. Methods: Patients' DICM data of ankle via CT
      examinations were introduced into the MIMICS software to design the personalized
      guides. Two 2mm Kirschner wires were drilled with the help of the guides; the C
      arm fluoroscopy was used to confirm the position of the wires before applying the
      cannulated screws. The patients who underwent ankle arthrodesis were divided into
      two groups. The experimental group adopted the 3D-printed personalized guides,
      while the control group received traditional method, i.e., drilling the Kirschner
      wires according to the surgeon's previous experience. The times of completing
      drilling the Kirschner wires to correct position were compared between the two
      groups. Regular follow-ups were conducted to statistically analyze the
      differences in the ankle fusion time and AOFAS scores between the two groups.
      Results: 3D-printed personalized guides were successfully prepared. A total of 29
      patients were enrolled, 15 in the experimental group and 14 in the control group.
      It took 2.2 +/- 0.8 minutes to drill the Kirschner wires to correct position in
      the experimental group and 4.5 +/- 1.6 minutes in the control group (p=0.001). No
      obvious complications occurred in the two groups during and after surgery.
      Postoperative radiographs confirmed bony fusion in all cases. There were no
      significant differences in the fusion time (p=0.82) and AOFAS scores at 1 year
      postoperatively between the two groups (p=0.55). Conclusions: The application of
      3D-printed personalized guide in assisting the accurate drilling of Kirschner
      wire in ankle arthrodesis can shorten the operation time and reduce the
      intraoperative radiation. This technique does not affect the surgical outcome.
      Trial Registration Number: This study is registered on www.clinicaltrials.gov
      with NCT03626935.

PMID- 30276206
TI  - The Effectiveness of Remineralizing Agents on Dentinal Permeability.
AB  - The effectiveness of remineralizing agents in reducing dentine permeability by
      tubule occlusion using fluid filtration device functioning at 100 cmH2O (1.4 psi)
      pressure and SEM/EDX analysis were evaluated and compared. Seventy (n = 70)
      dentine discs of 1+/-0.2 mm width were prepared from sound permanent human
      molars. Fifty (n = 50) dentine discs were randomly divided into 5 groups (n =
      10): Group 1: GC Tooth Mousse Plus (Recaldent GC Corporation Tokyo, Japan), Group
      2: ClinproTM White Varnish (3M ESPE, USA), Group 3: Duraphat(r) Varnish (Pharbil
      Waltrop GmbH, Germany), Group 4: Colgate Sensitive Pro-ReliefTM dentifrice
      (Colgate Palmolive, Thailand), and Group 5: BiodentineTM (Septodont/UK). Dentine
      permeability was measured after treatment application at 10 minutes, artificial
      saliva immersion at 7 days, and citric acid challenge for 3 minutes. Data were
      analyzed by two-way repeated measures ANOVA. Dentine specimens (n = 20) were used
      for SEM/EDX analyses to obtain qualitative results on dentine morphology and
      surface deposits. Each treatment agent significantly reduced dentine permeability
      immediately after treatment application and created precipitates on treated
      dentine surfaces. All agents increased permeability values after 7 days of
      artificial saliva immersion except Clinpro White Varnish and Biodentine. Clinpro
      White Varnish exhibited significant resistance to acid challenge compared to
      others. Colgate Sensitive Pro-Relief dentifrice has a dual mechanism of action in
      reducing the dentine sensitivity.

PMID- 30276200
TI  - Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges.
AB  - Cisplatin is an antitumor drug used in the treatment of a wide variety of
      malignancies. However, its primary dose-limiting side effect is kidney injury,
      which is a major clinical concern. To help understand mechanisms involved in the
      development of kidney injury, cisplatin rodent model has been developed. Given
      the complex pathogenesis of kidney injury, which involves both local events in
      the kidney and interconnected and interdependent systemic effects in the body,
      cisplatin rodent model is indispensable in the investigation of underlying
      mechanisms and potential treatment strategies of both acute and chronic kidney
      injury. Cisplatin rodent model is well appreciated and widely used model due to
      its simplicity. It has many similarities to human cisplatin nephrotoxicity, which
      are mentioned in the paper. In spite of its simplicity and wide applicability,
      there are also traps that need to be taken into account when using cisplatin
      model. The present paper is aimed at giving a concise insight into the complex
      characteristics of cisplatin rodent model and heterogeneity of cisplatin dosage
      regimens as well as outlining factors that can severely influence the outcome of
      the model and the study. Challenges for future research are also mentioned.

PMID- 30276208
TI  - A Shallow Angle Short-Axis Out-of-Plane Approach Reduces the Rate of Posterior
      Wall Injuries in Central Venous Catheterization: A Simulation Study.
AB  - The short-axis out-of-plane approach (SAX-OOP) is commonly used in ultrasound
      guided internal jugular vein catheterization. However, this approach has a risk
      of posterior vein wall injuries. The authors hypothesized that a shallow angle of
      approach may reduce the rate of posterior wall injuries compared with the
      conventional steep angle approach. The present study aimed to evaluate whether a
      difference in the angle of approach of the needle affects the rate of posterior
      wall injuries. The present study was a randomized crossover-controlled trial
      involving 40 medical residents, conducted in the clinical training center at a
      hospital with a residency program. The primary outcome measure was the rate of
      posterior vessel wall injuries. Subjects received a didactic lecture during which
      the instructors taught three SAX-OOP techniques including the conventional free
      hand method (procedure C), a needle navigation system (procedure N), and a
      shallow puncture angle using a guidance system (procedure S). Participants were
      trained in these approaches under supervision and each technique tested in a
      simulation environment. Thirty-four of 40 residents had no previous experience
      with central venous catheterization and were included in the final analysis. The
      rate of posterior vessel wall injuries in procedure S (9%) was significantly
      lower than using the other approaches (procedure C, 53%; procedure N, 41%). In
      conclusion, a shallow angle of approach using the SAX-OOP technique resulted in
      significantly fewer posterior vein wall injuries in central venous
      catheterization compared with steep angle techniques.

PMID- 30276207
TI  - Optimization of Ultrasound-Assisted Extraction Followed by Macroporous Resin
      Purification for Maximal Recovery of Functional Components and Removal of Toxic
      Components from Ginkgo biloba Leaves.
AB  - In the present study, the process of ultrasound-assisted extraction (UAE)
      followed by macroporous resin purification was successfully developed to achieve
      maximal recovery of functional components (flavonoids and ginkgolides) with
      minimal contents of toxic components (alkylphenols) from Ginkgo biloba leaves.
      Three effective extracted factors including HAc%, EtOH%, and UAE power were
      screened by Plackett-Burman design (PBD). The important variables were further
      optimized by rotatable central composite design (RCCD). By combination of PBD and
      RCCD, the resulting optimal UAE conditions were as follows: HAc% of 1.8%, EtOH%
      of 63%, ultrasound power of 303 W, G. biloba leaves powder amount of 1.0 g
      (solvent-to-solid ratio 40 mL/g), particle size of 60 mesh, extraction time of 40
      min, and extraction temperature of 45 degrees C. Under the optimum conditions,
      the yield of flavonoids was 25.1 +/- 0.81 mg/g, ginkgolides was 10.6 +/- 0.57
      mg/g, and alkylphenols was 3.96 +/- 0.31 mg/g. Moreover, the further enriching
      the functional components and removing toxic components from the obtained
      extracts of G. biloba leaves using the above optimum UAE condition was
      successfully achieved by macroporous resin DA-201. After column adsorption and
      desorption on DA-201, the content of total flavonoids was 36.51 +/- 1.53%,
      ginkgolides was 13.24 +/- 0.85%, and alkylphenols was 7.0 +/- 1.0 MUg/g from the
      obtained dry extracts (drug to extract ratio of 45-50:1) of G. biloba leaves
      which were complied with Chinese pharmacopoeias.

PMID- 30276209
TI  - Atrial Structural Remodeling Gene Variants in Patients with Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is a common arrhythmia for which the genetic studies
      mainly focused on the genes involved in electrical remodeling, rather than left
      atrial muscle remodeling. To identify rare variants involved in atrial myopathy
      using mutational screening, a high-throughput next-generation sequencing (NGS)
      workflow was developed based on a custom AmpliSeqTM panel of 55 genes potentially
      involved in atrial myopathy. This workflow was applied to a cohort of 94 patients
      with AF, 76 with atrial dilatation and 18 without. Bioinformatic analyses used
      NextGENe(r) software and in silico tools for variant interpretation. The AmpliSeq
      custom-made panel efficiently explored 96.58% of the targeted sequences. Based on
      in silico analysis, 11 potentially pathogenic missense variants were identified
      that were not previously associated with AF. These variants were located in genes
      involved in atrial tissue structural remodeling. Three patients were also
      carriers of potential variants in prevalent arrhythmia-causing genes, usually
      associated with AF. Most of the variants were found in patients with atrial
      dilatation (n=9, 82%). This NGS approach was a sensitive and specific method that
      identified 11 potentially pathogenic variants, which are likely to play roles in
      the predisposition to left atrial myopathy. Functional studies are needed to
      confirm their pathogenicity.

PMID- 30276210
TI  - Incidence, Risk Factors, and Epidemiology of Cystic Echinococcosis: A Complex
      Socioecological Emerging Infectious Disease in Khyber Pakhtunkhwa, Province of
      Pakistan.
AB  - Cystic echinococcosis is a serious zoonotic disease caused by Echinococcus
      granulosus species complex. The current study is the first attempt to determine
      the level of infection in domestic livestock and to explore the CE-related
      knowledge and awareness among livestock farmers in different districts of Khyber
      Pakhtunkhwa, province of Pakistan. A total of 1297 animals were examined for
      hydatid cysts including 538 cows, 428 buffaloes, 208 sheep, and 123 goats, at
      different slaughter houses in different districts of Khyber Pakhtunkhwa in 2
      years from September 2015 to September 2017. For epidemiological investigations,
      prevalence in association with various factors (climate, age, and gender), organ
      specificity, types of cysts (fertile, sterile, or calcified), and viability of
      cysts parameters was recorded. Basing on the results obtained, areas with high
      prevalence were selected for further follow-ups and administration of
      questionnaires to the farmers and dog owners, to provide baseline data about this
      parasitic disease and to identify potential areas of emergence with
      correspondence animal and of public health significance. The finding of this
      study revealed the presence of CE in livestock of KP, Pakistan. The prevalence of
      hydatid cysts was the highest in buffaloes (15.88%) followed by cows (15.79%),
      sheep (15.38%), and goats (3.25%). Our investigation revealed close relationship
      between prevalence and animal age and gender in different months of the year.
      These findings also showed the highest prevalence of hydatid cysts in liver
      (63.49%), followed by lungs (23.80%) and mesentery (2.64%). Fertile and viable
      cysts were observed in all animal species except goats. The highest percentage of
      fertile and viable cysts was reported from the liver and lungs of sheep. For
      evaluation of risk factors, a total of 384 respondents were investigated. The
      results of current study revealed that 97.9% of farmers are not familiar with CE
      and transmission of this infection from dogs to human and livestock. The present
      study shows that CE will continue to be of medical and veterinary importance in
      Pakistan.

PMID- 30276211
TI  - A Combined Fully Convolutional Networks and Deformable Model for Automatic Left
      Ventricle Segmentation Based on 3D Echocardiography.
AB  - Segmentation of the left ventricle (LV) from three-dimensional echocardiography
      (3DE) plays a key role in the clinical diagnosis of the LV function. In this
      work, we proposed a new automatic method for the segmentation of LV, based on the
      fully convolutional networks (FCN) and deformable model. This method implemented
      a coarse-to-fine framework. Firstly, a new deep fusion network based on feature
      fusion and transfer learning, combining the residual modules, was proposed to
      achieve coarse segmentation of LV on 3DE. Secondly, we proposed a method of
      geometrical model initialization for a deformable model based on the results of
      coarse segmentation. Thirdly, the deformable model was implemented to further
      optimize the segmentation results with a regularization item to avoid the leakage
      between left atria and left ventricle to achieve the goal of fine segmentation of
      LV. Numerical experiments have demonstrated that the proposed method outperforms
      the state-of-the-art methods on the challenging CETUS benchmark in the
      segmentation accuracy and has a potential for practical applications.

PMID- 30276212
TI  - Small Molecule Inhibitor of Type Three Secretion System Belonging to a Class 2,4
      disubstituted-4H-[1,3,4]-thiadiazine-5-ones Improves Survival and Decreases
      Bacterial Loads in an Airway Pseudomonas aeruginosa Infection in Mice.
AB  - Pseudomonas aeruginosa is a cause of high mortality in burn, immunocompromised,
      and surgery patients. High incidence of antibiotic resistance in this pathogen
      makes the existent therapy inefficient. Type three secretion system (T3SS) is a
      leading virulence system of P. aeruginosa that actively suppresses host
      resistance and enhances the severity of infection. Innovative therapeutic
      strategies aiming at inhibition of type three secretion system of P. aeruginosa
      are highly attractive, as they may reduce the severity of clinical manifestations
      and improve antibacterial immune responses. They may also represent an attractive
      therapy for antibiotic-resistant bacteria. Recently our laboratory developed a
      new small molecule inhibitor belonging to a class 2,4-disubstituted-4H-[1,3, 4]
      thiadiazine-5-ones, Fluorothiazinon (FT), that effectively suppressed T3SS in
      chlamydia and salmonella in vitro and in vivo. In this study, we evaluate the
      activity of FT towards antibiotic-resistant clinical isolates of P. aeruginosa
      expressing T3SS effectors ExoU and ExoS in an airway infection model. We found
      that FT reduced mortality and bacterial loads and decrease lung pathology and
      systemic inflammation. In addition, we show that FT inhibits the secretion of
      ExoT and ExoY, reduced bacteria cytotoxicity, and increased bacteria
      internalization in vitro. Overall, FT shows a strong potential as an
      antibacterial therapy of antibiotic-resistant P. aeruginosa infection.

PMID- 30276213
TI  - MultiParametric Magnetic Resonance Imaging-Based Nomogram for Predicting Prostate
      Cancer and Clinically Significant Prostate Cancer in Men Undergoing Repeat
      Prostate Biopsy.
AB  - Objective: To develop and internally validate nomograms based on multiparametric
      magnetic resonance imaging (mpMRI) to predict prostate cancer (PCa) and
      clinically significant prostate cancer (csPCa) in patients with a previous
      negative prostate biopsy. Materials and Methods: The clinicopathological
      parameters of 231 patients who underwent a repeat systematic prostate biopsy and
      mpMRI were reviewed. Based on Prostate Imaging and Reporting Data System, the
      mpMRI results were assigned into three groups: Groups "negative," "suspicious,"
      and "positive." Two clinical nomograms for predicting the probabilities of PCa
      and csPCa were constructed. The performances of nomograms were assessed using
      area under the receiver operating characteristic curves (AUCs), calibrations, and
      decision curve analysis. Results: The median PSA was 15.03 ng/ml and abnormal DRE
      was presented in 14.3% of patients in the entire cohort. PCa was detected in 75
      patients (32.5%), and 59 (25.5%) were diagnosed with csPCa. In multivariate
      analysis, age, prostate-specific antigen (PSA), prostate volume (PV), digital
      rectal examination (DRE), and mpMRI finding were significantly independent
      predictors for PCa and csPCa (all p < 0.01). Of those patients diagnosed with PCa
      or csPCa, 20/75 (26.7%) and 18/59 (30.5%) had abnormal DRE finding, respectively.
      Two mpMRI-based nomograms with super predictive accuracy were constructed (AUCs =
      0.878 and 0.927, p < 0.001), and both exhibited excellent calibration. Decision
      curve analysis also demonstrated a high net benefit across a wide range of
      probability thresholds. Conclusion: mpMRI combined with age, PSA, PV, and DRE can
      help predict the probability of PCa and csPCa in patients who underwent a repeat
      systematic prostate biopsy after a previous negative biopsy. The two nomograms
      may aid the decision-making process in men with prior benign histology before the
      performance of repeat prostate biopsy.

PMID- 30276214
TI  - Corrigendum to "Patient-Specific CT-Based Instrumentation versus Conventional
      Instrumentation in Total Knee Arthroplasty: A Prospective Randomized Controlled
      Study on Clinical Outcomes and In-Hospital Data".
AB  - [This corrects the article DOI: 10.1155/2015/165908.].

PMID- 30276215
TI  - Corrigendum to "Expression of HE4 in Endometrial Cancer and Its Clinical
      Significance".
AB  - [This corrects the article DOI: 10.1155/2015/437468.].

PMID- 30276216
TI  - Therapeutic Potential of Fulvic Acid in Chronic Inflammatory Diseases and
      Diabetes.
AB  - Chronic inflammatory diseases like diabetes are on a rise in the Western world.
      Based on the tsunami of new cases every year, new therapeutic measures must be
      considered. A promising avenue might involve the attenuation of underlying
      inflammation through natural health products (NHPs). This is because most NHPs
      have a rich history in traditional medicine and might be considered safer under
      appropriate doses and conditions. However, the biggest impediment in NHP research
      is that rarely do these products come with verified health benefits or dosing
      schedules established through modern scientific research. Fulvic acid (FvA), one
      such NHP, comes from humic substances produced by microorganisms in soil.
      Traditional medicine and modern research claim FvA can modulate the immune
      system, influence the oxidative state of cells, and improve gastrointestinal
      function; all of which are hallmarks of diabetes. This minireview outlines the
      available peer-reviewed research on FvA and examines its anecdotal health claims.
      We show that although available research has been minimal, there is substantial
      evidence to pursue FvA research in preventing chronic inflammatory diseases,
      including diabetes.

PMID- 30276217
TI  - Simvastatin-Induced Insulin Resistance May Be Linked to Decreased Lipid Uptake
      and Lipid Synthesis in Human Skeletal Muscle: the LIFESTAT Study.
AB  - Background: A prevalent side-effect of simvastatin is attenuated glucose
      homeostasis. The underlying mechanism is unknown, but impaired lipid metabolism
      may provide the link. The aim of this study was to investigate whether
      simvastatin-treated patients had a lower capacity to oxidize lipids and reduced
      expression of the major proteins regulating lipid uptake, synthesis, lipolysis,
      and storage in skeletal muscle than matched controls. Materials and Methods: Ten
      men were treated with simvastatin (HbA1c: 5.7 +/- 0.1%), and 10 healthy men
      (HbA1c: 5.2 +/- 0.1%) underwent an oral glucose tolerance test and a muscle
      biopsy was obtained. Fat oxidation rates were measured at rest and during
      exercise. Western blotting was used to assess protein content. Results: Patients
      treated with simvastatin had impaired glucose tolerance compared with control
      subjects, but fat oxidation at rest and during exercise was compatible. Skeletal
      muscle protein content of CD36, lipoprotein lipase (LPL), and diacylglycerol
      acyltransferase (DGAT) 1 were lower, and DGAT 2 tended to be lower in patients
      treated with simvastatin. Conclusions: Patients treated with simvastatin had a
      reduced capacity to synthesize FA and diacylglycerol (DAG) into triacylglycerol
      in skeletal muscle compared to matched controls. Decreased lipid synthesis
      capacity may lead to accumulation of lipotoxic intermediates (FA and DAG) and
      hence impair glucose tolerance.

PMID- 30276218
TI  - OSU-T315 as an Interesting Lead Molecule for Novel B Cell-Specific Therapeutics.
AB  - B cells are pathogenic in various disease processes and therefore represent an
      interesting target for the development of novel immunosuppressants. In the search
      for new therapeutic molecules, we utilized an in vitro B cell activation assay
      with ODN2006-stimulated Namalwa cells to screen a chemical library of small
      molecules for B cell modulating effects. OSU-T315, described as an inhibitor of
      integrin-linked kinase (ILK), was hereby identified as a hit. On human and murine
      primary B cells, OSU-T315 potently suppressed the proliferation and the
      production of antibodies and cytokines upon stimulation, suggesting that ILK
      could be a promising target in the modulation of B cell activity. Mice with B
      cell-specific knockout of ILK were generated. Surprisingly, knockout of ILK in
      murine B cells did not affect B cell function as assessed by several in vivo and
      ex vivo B cell assays and did not alter the B cell immunosuppressive activity of
      OSU-T315. In conclusion, OSU-T315 displays potency as B cell modulator, probably
      through a mechanism of action independent of ILK, and might serve as lead drug
      molecule for the development of novel B cell-selective drugs.

PMID- 30276219
TI  - Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage
      M1/M2 Polarization via the Smad2/Smad3 Pathway.
AB  - Objective: This study investigated the alterations in macrophage polarization in
      patients with endometriosis as well as the underlying molecular mechanisms.
      Methods: Peritoneal washings, serum samples, and endometrial tissues were
      collected from endometriosis patients and control subjects. Endometrial stromal
      cells (ESCs) were isolated from endometrial tissue, and conditioned medium was
      prepared by treating ESCs with or without various concentrations of interleukin-
      (IL-) 6, estrogen, or progestin. The frequencies of CD86+ and CD163+ cells and
      expression levels of these markers as well as the cytokines IL-12 and IL-10 were
      measured in THP-1- (human monocytic leukemia cell) derived macrophages. Results:
      There was a decrease in the percentage of CD86+ macrophages in the peritoneal
      wash solution of patients with endometriosis. Ectopic endometrial homogenates
      could promote M1 to M2 macrophage polarization in response to lipopolysaccharide
      (LPS), as evidenced by the increased percentage of CD163+ macrophages and
      increased IL-10 expression as well as a decreased percentage of CD86+ cells and
      lower IL-12 expression. In contrast, addition of serum from women with
      endometriosis to THP-1 cells resulted in the polarization of macrophages towards
      both M1 and M2 phenotypes. Upregulation of Smad2/Smad3 in macrophages upon
      exposure to eutopic and ectopic endometrial homogenates as well as serum of women
      with endometriosis was observed, and blockage of Smad2/Smad3 with their inhibitor
      SB431542 could reverse the macrophage polarization from M1 to M2. Conditioned
      medium induced by IL-6, but neither estrogen nor progestin, could facilitate M2
      polarization. Neutralization of IL-6 diminished macrophage M2 polarization in
      endometriosis. Conclusion: This study provides detailed evidence supporting
      alterations in M1 to M2 macrophage polarization that may contribute to the
      initiation as well as progression of endometriosis.

PMID- 30276220
TI  - Quadriceps Strength Deficits After a Femoral Nerve Block Versus Adductor Canal
      Block for Anterior Cruciate Ligament Reconstruction: A Prospective, Single
      Blinded, Randomized Trial.
AB  - Background: Peripheral nerve blocks, particularly femoral nerve blocks (FNBs),
      are commonly performed for anterior cruciate ligament (ACL) reconstruction.
      However, associated quadriceps muscle weakness after FNBs is well described and
      may occur for up to 6 months postoperatively. The adductor canal block (ACB) has
      emerged as a viable alternative to the FNB, theoretically causing less quadriceps
      weakness during the immediate postoperative period, as it bypasses the majority
      of the motor fibers of the femoral nerve that branch off proximal to the adductor
      canal. Purpose/Hypothesis: This study sought to identify if a difference in
      quadriceps strength exists after an ACB or FNB for ACL reconstruction beyond the
      immediate postoperative period. Beyond the immediate postoperative period, we
      anticipated no difference in quadriceps strength between patients who received
      ACBs or FNBs for ACL reconstruction. Study Design: Randomized controlled trial;
      Level of evidence, 1. Methods: A total of 102 patients undergoing primary ACL
      reconstruction using a variety of graft types were enrolled between November 2015
      and April 2016. All patients were randomized to receive an ACB or FNB before
      surgery, and the surgeon was blinded to the block type. All patients underwent
      aggressive rehabilitation without functional bracing postoperatively. The time to
      the first straight-leg raise was reported by the patient. Isokinetic strength
      testing was performed at 3 and 6 months postoperatively. Results: Data for 73
      patients were analyzed. There was no significant difference in patient
      demographics of age, body mass index, sex, or tourniquet time between the FNB (n
      = 35) and ACB (n = 38) groups. The mean time to the first straight-leg raise was
      similar, at 13.1 +/- 1.0 hours for the FNB group and 15.5 +/- 1.2 hours for the
      ACB group (P = .134). The mean extension torque at 60 deg/s increased
      significantly for both the ACB (53.7% +/- 3.4% to 68.3% +/- 2.9%; P = .008) and
      the FNB (53.3% +/- 3.3% to 68.5% +/- 4.1%; P = .006) groups from 3 to 6 months
      postoperatively. There was also no significant difference in mean extension
      torque at 60 deg/s or 180 deg/s between the FNB and ACB groups at 3 and 6 months.
      There were no significant differences in postoperative complications (infection,
      arthrofibrosis, retear) between groups. Conclusion: Although prior studies have
      shown immediate postoperative benefits of ACBs compared with FNBs, with a faster
      return of quadriceps strength, in the current study there was no statistically or
      clinically significant difference in quadriceps strength at 3 and 6 months
      postoperatively in patients who received ACBs or FNBs for ACL reconstruction.

PMID- 30276221
TI  - Repeated False-Positive HIV Test Results in a Patient Taking HIV Pre-Exposure
      Prophylaxis.
AB  - Regular HIV testing is required to ensure the safety of HIV pre-exposure
      prophylaxis (PrEP). We describe and discuss a series of false-positive HIV test
      results from an individual receiving PrEP. The expansion of PrEP will likely
      result in greater numbers of false-positive test results that may pose challenges
      for interpretation.

PMID- 30276222
TI  - Evaluation of deep learning methods for parotid gland segmentation from CT
      images.
AB  - The segmentation of organs at risk is a crucial and time-consuming step in
      radiotherapy planning. Good automatic methods can significantly reduce the time
      clinicians have to spend on this task. Due to its variability in shape and low
      contrast to surrounding structures, segmenting the parotid gland is challenging.
      Motivated by the recent success of deep learning, we study the use of two
      dimensional (2-D), 2-D ensemble, and three-dimensional (3-D) U-Nets for
      segmentation. The mean Dice similarity to ground truth is ~0.83 for all three
      models. A patch-based approach for class balancing seems promising for false
      positive reduction. The 2-D ensemble and 3-D U-Net are applied to the test data
      of the 2015 MICCAI challenge on head and neck autosegmentation. Both deep
      learning methods generalize well onto independent data (Dice 0.865 and 0.88) and
      are superior to a selection of model- and atlas-based methods with respect to the
      Dice coefficient. Since appropriate reference annotations are essential for
      training but often difficult and expensive to obtain, it is important to know how
      many samples are needed for training. We evaluate the performance after training
      with different-sized training sets and observe no significant increase in the
      Dice coefficient for more than 250 training cases.

PMID- 30276223
TI  - Salvage mastectomy for local recurrence and second ipsilateral autologous breast
      reconstruction using a perforator flap from a different donor site.
AB  - Only one case of second ipsilateral autologous reconstruction for the same breast
      that had previously undergone reconstruction has been reported. Here we present a
      patient who underwent breast reconstruction twice using free flap from different
      donor sites, using a buttock after a local recurrence following the previous
      reconstruction with a lower abdomen.

PMID- 30276224
TI  - The Role of Learning in Threat Imminence and Defensive Behaviors.
AB  - Life threatening situations as urgent as defending against a predator precludes
      the use of slow trial and error strategies. Natural selection has led to the
      evolution of a behavioral system that has 3 critical elements. 1) When it is
      activated it limits the behaviors available to the organism to a set of prewired
      responses that have proven over phylogeny to be effective at defense. 2) A rapid
      learning system, called Pavlovian fear conditioning, that has the ability to
      immediately identify threats and promote prewired defensive behaviors. 3) That
      learning system has the ability to integrate several informational dimensions to
      determine threat imminence and this allows the organism to match the most
      effective defensive behavior to the current situation. The adaptive significance
      of conscious experiential states is also considered.

PMID- 30276225
TI  - Data on expert system-econometric entropy informatics model for adjudicating
      residential building project costs.
AB  - This data article presents an expert system and econometric entropy-based
      informatics model for residential building project for cost judgment and
      decisions in residential building project. The data was obtained using purposive
      sampling technique to select projects completed between 2009 and 2011in Lagos
      state Nigeria, the project were examined for their cost centres. Also, As-built
      cost of one thousand(1000) samples of trained As-built cost of residential
      building projects trained with Neural network with Levenberg Marqua after being
      adjusted and modified with econometric factors like inflation index, cost entropy
      and entropy factor to stabilized the data and were used to form and train neural
      network used. Probability technique was used to generate risk impact matrix and
      influence of entropy on the cost centres. A parametric model similar to hedonic
      models was generated using the utility parameters within the early and late
      elemental dichotomy. The model was validated through comparative analysis of the
      econometric loading attributes using Monte Carlo technique of SPSS software
      extracting the contingency coefficient. The data of the model can provide
      solution to the problems of knowing the cost implication of a future project and
      also enable a builder or contactor load cost implication of an unseen
      circumstance even on occasion of deferred cost reimbursement.

PMID- 30276226
TI  - Morphological and phytochemical data of Vanilla species in Mexico.
AB  - This systematic determination of morphological and phytochemical data was
      conducted with the purpose of conserving and identifying the phylogenetic
      relationship among the Vanilla species of the Totonacapan region in Mexico to
      increase awareness of the genetic biodiversity. Samples of Vanilla planifolia, V.
      planifolia cv. "oreja de burro", V. pompona, V. insignis, and V. inodora, are
      distributed across 19 municipalities of the State of Veracruz and 19
      municipalities of the State of Puebla. Morphological data parameters were
      determined in situ and included leaf length, leaf width, leaf thickness, stem
      diameter, stem thickness, node distance, stem texture degree, flower colour
      intensity, and fruit length. Similarly, alkaloids, tannins, saponins, phenols,
      flavonoids, and terpenes were determined by specifically phytochemical tests and
      quantified by thin layer chromatography. Both, morphological and phytochemical
      data parameters, were successfully used in assembling dendrograms by using the
      Euclidian distance method and by principal component analysis.

PMID- 30276227
TI  - Survey dataset on occupants' satisfaction with housing and life in public
      residential estates in Ogun State, Nigeria.
AB  - This article describes the data associated with the research paper entitled
      "Subjective life satisfaction in public housing in urban areas of Ogun State" by
      Ibem and Amole (2013). A multistage sampling technique and questionnaire were
      used to extract data from occupants in 517 dwelling units in ten selected
      government mass housing schemes located in five urban centers in Ogun State,
      Nigeria. The dataset has 57 different variables describing households'
      demographics, dwelling units' features, supply of basic services, and
      neighbourhood environment in the residential estates. In addition, it also
      contains variables used to assess residential satisfaction and satisfaction with
      life. The Statistical Package of the Social Sciences (SPSS) file, descriptive
      statistics for all the variables and questionnaire used to derive the data are
      provided in this article. The dataset will enhance understanding of the main
      research findings and conclusions.

PMID- 30276228
TI  - 18S rDNA sequencing data of benthic polychaetes from the Eastern Arabian Sea.
AB  - The limited DNA sequence data of the polychaetes species are available from the
      Eastern Arabian Sea. We have sequenced 18S rDNA gene from 54 polychaetes species
      and 37 species identified up to the species level. The DNA bar-coding data
      provides for molecular identification of benthic polychaetes that will provide
      imminent into drivers of species diversity in the Eastern Arabian Sea. The 18S
      rDNA sequence data set is made publicly available to enable critical or extended
      analyzes of DNA bar-coding.

PMID- 30276229
TI  - Additional data on damage reduction strategies against chemical accidents by
      using a mitigation barrier in Korean chemical risk management.
AB  - This paper describes data of post-release mitigation strategy and its effect for
      chemical process. The data in this paper is associated with the article entitled
      "Damage reduction strategies against chemical accidents by using a mitigation
      barrier in Korean chemical risk management". The data includes computational
      fluid dynamics (CFD) simulation result for vapor cloud explosion accident
      scenarios. Simulations with suggested mitigation strategy and without the
      mitigation strategy were conducted. The data is expected to good reference for
      developing chemical plant mitigation plan.

PMID- 30276230
TI  - Characterization of the diethyl phthalate-degrading bacterium Sphingobium
      yanoikuyae SHJ.
AB  - A newly isolated bacterial strain SHJ was found to be capable of degrading
      diethyl phthalate (DEP) very efficiently. Its growth characteristics and 16S rDNA
      gene sequence were analyzed. Its whole genome was also sequenced. Strain SHJ was
      identified as Sphingobium yanoikuyae SHJ.

PMID- 30276231
TI  - Carotid artery plaque uptake of 11C-PK11195 inversely correlates with circulating
      monocytes and classical CD14++CD16- monocytes expressing HLA-DR.
AB  - Background: We explored the relation between blood concentrations of
      monocyte/lymphocyte subsets and carotid artery plaque macrophage content,
      measured by positron emission tomography (PET) with 11C-PK11195. Methods and
      results: In 9 patients with carotid plaques we performed 11C-PK11195-PET/computed
      tomography angiography imaging and measurement of absolute concentrations and
      frequencies of circulating monocytes and T-cell subsets. Plaque standardized
      uptake value (SUV) for 11C-PK11195 was negatively correlated with concentrations
      of total monocytes (r = -0.58, p = 0.05) and CD14++CD16-HLA-DR+ classical subset
      (r = -0.82, p = 0.005). These correlations hold true also in relation to plaque
      target to background ratio. No correlation was observed between plaque SUV and
      CD3+T lymphocytes, CD4+T lymphocytes nor with activated CD3+CD4+T cells
      expressing HLA-DR. Conclusions: We first demonstrated a reduction in the absolute
      concentration of monocytes and particularly in classical monocytes expressing HLA
      DR in the presence of an increased uptake of 11C-PK11195 in carotid plaques. The
      present work, despite being a pilot study comprising only a small number of
      subjects provides new insights in the search for specific cellular biomarkers
      with potential diagnostic and prognostic value in patients with a known carotid
      plaque.

PMID- 30276233
TI  - Help cure Parkinson's disease: please don't waste the Golden Year.

PMID- 30276235
TI  - Synthetic Lava Brings Eruption into the Lab.

PMID- 30276236
TI  - The Secret Life of Fat Cells.

PMID- 30276232
TI  - Molecular mechanisms and genetic regulation in atherosclerosis.
AB  - Atherosclerosis (AS) manifested by lipid accumulation, extracellular matrix
      protein deposition, and calcification in the intima and media of the large to
      medium size arteries promoting arterial stiffness and reduction of elasticity. It
      has been accepted that AS leads to increased morbidity and mortality worldwide.
      Recent studies indicated that genetic abnormalities play an important role in the
      development of AS. Specific genetic mutation and histone modification have been
      found to induce AS formation. Furthermore, specific RNAs such as microRNAs and
      circular RNAs have been identified to play a crucial role in the progression of
      AS. Nevertheless, the mechanisms by which genetic mutation, DNA and histone
      modification, microRNAs and circular RNA induce AS still remain elusive. This
      review describes specific mechanisms and pathways through which genetic mutation,
      DNA and histone modification, microRNAs and circular RNA instigate AS. This
      review further provides a therapeutic strategic direction for the treatment of AS
      targeting genetic mechanisms.

PMID- 30276234
TI  - Androgen receptor expression in normal breast tissue and subsequent breast cancer
      risk.
AB  - Sex steroid hormone signaling is critical in the development of breast cancers,
      although the role of the androgen receptor remains unclear. This study evaluated
      androgen receptor (AR) expression in normal breast tissue as a potential marker
      of breast cancer risk. We conducted a nested case-control study of women with
      benign breast disease (BBD) within the Nurses' Health Studies. Epithelial AR
      expression was assessed by immunohistochemistry in normal tissue from the BBD
      biopsy and the percent of positive nuclei was estimated in ordinal categories of
      10% for 78 breast cancer cases and 276 controls. Logistic regression models
      adjusting for the matching factors and BBD lesion type were used to calculate
      odds ratios (ORs) for the association between AR expression (tertiles: <=10%, 11
      30%, and >30%) and breast cancer risk. AR expression in normal breast tissue was
      not associated with subsequent breast cancer risk (ORT3vsT1 = 0.9, 95% CI = 0.4
      1.8, p trend = 0.68). In comparison with low AR/low ER women, ORs of 0.4 (95% CI
      = 0.1-1.2) for high AR/high ER women, 1.8 (95% CI = 0.4-7.8) for low AR/high ER
      women, and 0.7 (95% CI = 0.3-1.6) for high AR/low ER women were observed (p
      interaction = 0.21). Ki67 did not modify the association between AR expression
      and breast cancer risk (p interaction = 0.75). There was little evidence for an
      overall association between AR expression in normal breast tissue and breast
      cancer risk. These findings did not show that the AR association varied by Ki67
      expression in normal breast tissue, though there was suggestive heterogeneity by
      ER expression.

PMID- 30276237
TI  - CdSe Semiconductor Nanocrystals: The Surface and the Core.

PMID- 30276238
TI  - Forwarding Molecular Design of Heterogeneous Catalysts.

PMID- 30276239
TI  - Next-Generation Materials via Orthogonal Stimuli.

PMID- 30276240
TI  - Accelerating Photofunctional Molecule Discovery with Artificial Intelligence.

PMID- 30276241
TI  - Size Determines Efficacy of Nanoparticle Magnetoresistance.

PMID- 30276242
TI  - Heterogeneous Gold Catalysis.
AB  - Catalysis is at the heart of many manufacturing processes and underpins provision
      of the goods and infrastructure necessary for the effective wellbeing of society;
      catalysis continues to play a key role in the manufacture of chemical
      intermediates and final products. There is a continuing need to design new
      effective catalysts especially with the drive toward using sustainable resources.
      The identification that gold is an exceptionally effective catalyst has paved the
      way for a new class of active heterogeneous and homogeneous catalysts for a broad
      range of reactions. As a heterogeneous catalyst gold is the most active catalyst
      for the oxidation of carbon monoxide at ambient temperature. It is also the most
      effective catalyst for the synthesis of vinyl chloride by acetylene
      hydrochlorination, and a gold catalyst has recently been commercialized in China
      for this reaction. In this outlook the nature of the active gold species for
      these two reactions will be explored.

PMID- 30276243
TI  - Bioinspired Designs of Superhydrophobic and Superhydrophilic Materials.
AB  - Bioinspired designs of superhydrophobic and superhydrophilic materials have been
      an important and fascinating area of research in recent years for their extensive
      potential application prospects from industry to our daily life. Despite
      extensive progress, existing research achievements are far from real
      applications. From biomimetic performance to service life, the related research
      has faced serious problems at present. A timely outlook is therefore necessary to
      summarize the existing research, to discuss the challenges faced, and to propose
      constructive advice for the ongoing scientific trend. Here, we comb the process
      of development of bioinspired superhydrophobic and superhydrophilic materials at
      first. Then, we also describe how to design artificial superhydrophobic and
      superhydrophilic materials. Furthermore, current challenges faced by bioinspired
      designs of superhydrophobic and superhydrophilic materials are pointed out,
      separately, and the possible solutions are discussed. Emerging applications in
      this field are also briefly considered. Finally, the development trend within
      this field is highlighted to lead future research.

PMID- 30276245
TI  - Hunting for Organic Molecules with Artificial Intelligence: Molecules Optimized
      for Desired Excitation Energies.
AB  - This work presents a proof-of-concept study in artificial-intelligence-assisted
      (AI-assisted) chemistry where a machine-learning-based molecule generator is
      coupled with density functional theory (DFT) calculations, synthesis, and
      measurement. Although deep-learning-based molecule generators have shown promise,
      it is unclear to what extent they can be useful in real-world materials
      development. To assess the reliability of AI-assisted chemistry, we prepared a
      platform using a molecule generator and a DFT simulator, and attempted to
      generate novel photofunctional molecules whose lowest excited states lie at
      desired energetic levels. A 10 day run on the 12-core server discovered 86
      potential photofunctional molecules around target lowest excitation levels,
      designated as 200, 300, 400, 500, and 600 nm. Among the molecules discovered, six
      were synthesized, and five were confirmed to reproduce DFT predictions in
      ultraviolet visible absorption measurements. This result shows the potential of
      AI-assisted chemistry to discover ready-to-synthesize novel molecules with modest
      computational resources.

PMID- 30276246
TI  - Phoenics: A Bayesian Optimizer for Chemistry.
AB  - We report Phoenics, a probabilistic global optimization algorithm identifying the
      set of conditions of an experimental or computational procedure which satisfies
      desired targets. Phoenics combines ideas from Bayesian optimization with concepts
      from Bayesian kernel density estimation. As such, Phoenics allows to tackle
      typical optimization problems in chemistry for which objective evaluations are
      limited, due to either budgeted resources or time-consuming evaluations of the
      conditions, including experimentation or enduring computations. Phoenics proposes
      new conditions based on all previous observations, avoiding, thus, redundant
      evaluations to locate the optimal conditions. It enables an efficient parallel
      search based on intuitive sampling strategies implicitly biasing toward
      exploration or exploitation of the search space. Our benchmarks indicate that
      Phoenics is less sensitive to the response surface than already established
      optimization algorithms. We showcase the applicability of Phoenics on the
      Oregonator, a complex case-study describing a nonlinear chemical reaction
      network. Despite the large search space, Phoenics quickly identifies the
      conditions which yield the desired target dynamic behavior. Overall, we recommend
      Phoenics for rapid optimization of unknown expensive-to-evaluate objective
      functions, such as experimentation or long-lasting computations.

PMID- 30276244
TI  - Resolving the Core and the Surface of CdSe Quantum Dots and Nanoplatelets Using
      Dynamic Nuclear Polarization Enhanced PASS-PIETA NMR Spectroscopy.
AB  - Understanding the surface of semiconductor nanocrystals (NCs) prepared using
      colloidal methods is a long-standing goal of paramount importance for all their
      potential optoelectronic applications, which remains unsolved largely because of
      the lack of site-specific physical techniques. Here, we show that
      multidimensional 113Cd dynamic nuclear polarization (DNP) enhanced NMR
      spectroscopy allows the resolution of signals originating from different atomic
      and magnetic surroundings in the NC cores and at the surfaces. This enables the
      determination of the structural perfection, and differentiation between the
      surface and core atoms in all major forms of size- and shape-engineered CdSe NCs:
      irregularly faceted quantum dots (QDs) and atomically flat nanoplatelets,
      including both dominant polymorphs (zinc-blende and wurtzite) and their epitaxial
      nanoheterostructures (CdSe/CdS core/shell quantum dots and CdSe/CdS core/crown
      nanoplatelets), as well as magic-sized CdSe clusters. Assignments of the NMR
      signals to specific crystal facets of oleate-terminated ZB structured CdSe NCs
      are proposed. Significantly, we discover far greater atomistic complexity of the
      surface structure and the species distribution in wurtzite as compared to zinc
      blende CdSe QDs, despite an apparently identical optical quality of both QD
      polymorphs.

PMID- 30276247
TI  - Free Energy Landscape of the Complete Transport Cycle in a Key Bacterial
      Transporter.
AB  - PepTSo is a proton-coupled bacterial symporter, from the major facilitator
      superfamily (MFS), which transports di-/tripeptide molecules. The recently
      obtained crystal structure of PepTSo provides an unprecedented opportunity to
      gain an understanding of functional insights of the substrate transport
      mechanism. Binding of the proton and peptide molecule induces conformational
      changes into occluded (OC) and outward-facing (OF) states, which we are able to
      characterize using molecular dynamics (MD) simulations. The structural knowledge
      of the OC and OF state is important to fully understand the major energy barrier
      associated with the transport cycle. In order to gain functional insight into the
      interstate dynamics, we performed extensive all atom MD simulations. The Markov
      state model was constructed to identify the free energy barriers between the
      states, and kinetic information on intermediate pathways was obtained using the
      transition pathway theory (TPT). TPT shows that the OF state is obtained by the
      movement of TM1 and TM7 at the extracellular side approximately 12-16 A away from
      each other, and the inward movement of TM4 and TM10 at the intracellular halves
      to 3-4 A characterizes the OC state. Helix distance distributions obtained from
      MD simulations were compared with experimental double electron-electron resonance
      spectroscopy and were found to be in excellent agreement with previous studies.
      We also predicted the optimal positions for placement of methane thiosulfonate
      spin label probes to capture the slowest protein dynamics. Our finding sheds
      light on the conformational cycle of this key membrane transporter and the
      functional relationships between the multiple intermediate states.

PMID- 30276248
TI  - Rationalizing Steroid Interactions with Lipid Membranes: Conformations,
      Partitioning, and Kinetics.
AB  - Steroids have numerous physiological functions associated with cellular signaling
      or modulation of the lipid membrane structure and dynamics, and as such, they
      have found broad pharmacological applications. Steroid-membrane interactions are
      relevant to multiple steps of steroid biosynthesis and action, as steroids are
      known to interact with neurotransmitter or membrane steroid receptors, and
      steroids must cross lipid membranes to exert their physiological functions.
      Therefore, rationalizing steroid function requires understanding of steroid
      membrane interactions. We combined molecular dynamics simulations and isothermal
      titration calorimetry to characterize the conformations and the energetics of
      partitioning, in addition to the kinetics of flip-flop transitions and membrane
      exit, of 26 representative steroid compounds in a model lipid membrane. The
      steroid classes covered in this study include birth control and anabolic drugs,
      sex and corticosteroid hormones, neuroactive steroids, as well as steroids
      modulating the lipid membrane structure. We found that the conformational
      ensembles adopted by different steroids vary greatly, as quantified by their
      distributions of tilt angles and insertion depths into the membrane, ranging from
      well-defined steroid conformations with orientations either parallel or normal to
      the membrane, to wide conformational distributions. Surprisingly, despite their
      chemical diversity, the membrane/water partition coefficient is similar among
      most steroids, except for structural steroids such as cholesterol, leading to
      similar rates for exiting the membrane. By contrast, the rates of steroid flip
      flop vary by at least 9 orders of magnitude, revealing that flip-flop is the rate
      limiting step during cellular uptake of polar steroids. This study lays the
      ground for a quantitative understanding of steroid-membrane interactions, and it
      will hence be of use for studies of steroid biosynthesis and function as well as
      for the development and usage of steroids in a pharmacological context.

PMID- 30276249
TI  - End-On Bound Iridium Dinuclear Heterogeneous Catalysts on WO3 for Solar Water
      Oxidation.
AB  - Heterogeneous catalysts with atomically defined active centers hold great promise
      for high-performance applications. Among them, catalysts featuring active
      moieties with more than one metal atom are important for chemical reactions that
      require synergistic effects but are rarer than single atom catalysts (SACs). The
      difficulty in synthesizing such catalysts has been a key challenge. Recent
      progress in preparing dinuclear heterogeneous catalysts (DHCs) from homogeneous
      molecular precursors has provided an effective route to address this challenge.
      Nevertheless, only side-on bound DHCs, where both metal atoms are affixed to the
      supporting substrate, have been reported. The competing end-on binding mode,
      where only one metal atom is attached to the substrate and the other metal atom
      is dangling, has been missing. Here, we report the first observation that end-on
      binding is indeed possible for Ir DHCs supported on WO3. Unambiguous evidence
      supporting the binding mode was obtained by in situ diffuse reflectance infrared
      Fourier transform spectroscopy and high-angle annular dark-field scanning
      transmission electron microscopy. Density functional theory calculations provide
      additional support for the binding mode, as well as insights into how end-on
      bound DHCs may be beneficial for solar water oxidation reactions. The results
      have important implications for future studies of highly effective heterogeneous
      catalysts for complex chemical reactions.

PMID- 30276250
TI  - Expanding the Chemical Space of Biocompatible Fluorophores: Nanohoops in Cells.
AB  - The design and optimization of fluorescent molecules has driven the ability to
      interrogate complex biological events in real time. Notably, most advances in
      bioimaging fluorophores are based on optimization of core structures that have
      been known for over a century. Recently, new synthetic methods have resulted in
      an explosion of nonplanar conjugated macrocyclic molecules with unique optical
      properties yet to be harnessed in a biological context. Herein we report the
      synthesis of the first aqueous-soluble carbon nanohoop (i.e., a macrocyclic slice
      of a carbon nanotube prepared via organic synthesis) and demonstrate its
      bioimaging capabilities in live cells. Moreover, we illustrate that these
      scaffolds can be easily modified by well-established "click" chemistry to enable
      targeted live cell imaging. This work establishes the nanohoops as an exciting
      new class of macrocyclic fluorophores poised for further development as novel
      bioimaging tools.

PMID- 30276251
TI  - Surface Fluctuations Dominate the Slow Glassy Dynamics of Polymer-Grafted Colloid
      Assemblies.
AB  - Colloids grafted with a corona layer of polymers show glassy behavior that covers
      a wide range of fragilities, with this behavior being tunable through variations
      in grafting density and grafting chain length. We find that the corona roughness,
      which is maximized for long chain lengths and sparse grafting, is directly
      correlated to the concentration-dependence of the system relaxation time
      (fragility). Relatively rougher colloids result in stronger liquids because their
      rotational motions become orientationally correlated across the whole system even
      at low particle loadings leading to an essentially Arrhenius-like concentration
      dependence of the relaxation times near the glass transition. The smoother
      colloids do not show as much orientational correlation except at higher densities
      leading to fragile behavior. We therefore propose that these materials are an
      ideal model to study the physical properties of the glass transition.

PMID- 30276252
TI  - Molecular Simulation of Chemical Reaction Equilibrium by Computationally
      Efficient Free Energy Minimization.
AB  - The molecular simulation of chemical reaction equilibrium (CRE) is a challenging
      and important problem of broad applicability in chemistry and chemical
      engineering. The primary molecular-based approach for solving this problem has
      been the reaction ensemble Monte Carlo (REMC) algorithm [Turner et al. Molec.
      Simulation2008, 34, (2), 119-146], based on classical force-field methodology. In
      spite of the vast improvements in computer hardware and software since its
      original development almost 25 years ago, its more widespread application is
      impeded by its computational inefficiency. A fundamental problem is that its MC
      basis inhibits the implementation of significant parallelization, and its
      successful implementation often requires system-specific tailoring and the
      incorporation of special MC approaches such as replica exchange, expanded
      ensemble, umbrella sampling, configurational bias, and continuous fractional
      component methodologies. We describe herein a novel CRE algorithm (reaction
      ensemble molecular dynamics, ReMD) that exploits modern computer hardware and
      software capabilities, and which can be straightforwardly implemented for systems
      of arbitrary size and complexity by exploiting the parallel computing methodology
      incorporated within many MD software packages (herein, we use GROMACS for
      illustrative purposes). The ReMD algorithm utilizes these features in the context
      of a macroscopically inspired and generally applicable free energy minimization
      approach based on the iterative approximation of the system Gibbs free energy
      function by a mathematically simple convex ideal solution model using the
      composition at each iteration as a reference state. Finally, we additionally
      describe a simple and computationally efficient a posteriori method to estimate
      the equilibrium concentrations of species present in very small amounts relative
      to others in the primary calculation. To demonstrate the algorithm, we show its
      application to two classic example systems considered previously in the
      literature: the N2-O2-NO system and the ammonia synthesis system.

PMID- 30276253
TI  - Visualizing Structural Transformation and Guest Binding in a Flexible Metal
      Organic Framework under High Pressure and Room Temperature.
AB  - Understanding the effect of gas molecules on the framework structures upon gas
      sorption in porous materials is highly desirable for the development of gas
      storage and separation technologies. However, this remains challenging for
      flexible metal-organic frameworks (MOFs) which feature "gate-opening/gate
      closing" or "breathing" sorption behaviors under external stimuli. Herein, we
      report such a flexible Cd-MOF that exhibits "gating effect" upon CO2 sorption.
      The ability of the desolvated flexible Cd-MOF to retain crystal singularity under
      high pressure enables the direct visualization of the reversible closed-/open
      pore states before and after the structural transformation as induced by CO2
      adsorption/desorption through in situ single-crystal X-ray diffraction
      experiments. The binding sites of CO2 molecules within the flexible MOF under
      high pressure and room temperature have also been identified via combined in situ
      single-crystal X-ray diffraction and powder X-ray diffraction studies,
      facilitating the elucidation of the states observed during gate-opening/gate
      closing behaviors. Our work therefore lays a foundation to understand the high
      pressure gas sorption within flexible MOFs at ambient temperature, which will
      help to improve the design efforts of new flexible MOFs for applications in
      responsive gas sorption and separation.

PMID- 30276254
TI  - A Lamin-Binding Ligand Inhibits Homologous Recombination Repair of DNA Double
      Strand Breaks.
AB  - Nuclear lamins are type V intermediate filament proteins. Lamins, including LA,
      LB1, LB2, and LC, are the major protein components forming the nuclear lamina to
      support the mechanical stability of the mammalian cell nucleus. Increasing
      evidence has shown that LA participates in homologous recombination (HR) repair
      of DNA double-strand breaks (DSBs) . However, the mechanisms underlying this
      process are incompletely understood. We recently identified the first lamin
      binding ligand 1 (LBL1) that directly binds LA and inhibited cancer cell growth.
      We provided here further mechanistic investigations of LBL1 and revealed that LA
      interacts with the HR recombinase Rad51 to protect Rad51 from degradation. LBL1
      inhibits LA-Rad51 interaction leading to accelerated proteasome-mediated
      degradation of Rad51, culminating in inhibition of HR repair of DSBs. These
      results uncover a novel post-translational regulation of Rad51 by LA and suggest
      that targeting the LA-Rad51 axis may represent a promising strategy to develop
      cancer therapeutics.

PMID- 30276255
TI  - Chemogenetic Approach Using Ni(II) Complex-Agonist Conjugates Allows Selective
      Activation of Class A G-Protein-Coupled Receptors.
AB  - Investigating individual G-protein-coupled receptors (GPCRs) involved in various
      signaling cascades can unlock a myriad of invaluable physiological findings. One
      of the promising strategies for addressing the activity of each subtype of
      receptor is to design chemical turn-on switches on the target receptors. However,
      valid methods to selectively control class A GPCRs, the largest receptor family
      encoded in the human genome, remain limited. Here, we describe a novel approach
      to chemogenetically manipulate activity of engineered class A GPCRs carrying a
      His4 tag, using metal complex-agonist conjugates (MACs). This manipulation is
      termed coordination tethering. With the assistance of coordination bonds, MACs
      showed 10-100-fold lower EC50 values in the engineered receptors, compared with
      wild-type receptors. Such coordination tethering enabled selective activation of
      beta2-adrenoceptors and muscarinic acetylcholine receptors, without loss of
      natural receptor responses, in living mammalian cells, including primary cultured
      astrocytes. Our generalized, modular chemogenetic approach should facilitate more
      precise control and deeper understanding of individual GPCR signaling pathways in
      living systems.

PMID- 30276256
TI  - A Size Threshold for Enhanced Magnetoresistance in Colloidally Prepared CoFe2O4
      Nanoparticle Solids.
AB  - The phenomenon of granular magnetoresistance offers the promise of rapid
      functional materials discovery and high-sensitivity, low-cost sensing technology.
      Since its discovery over 25 years ago, a major challenge has been the preparation
      of solids composed of well-characterized, uniform, nanoscale magnetic domains.
      Rapid advances in colloidal nanochemistry now facilitate the study of more
      complex and finely controlled materials, enabling the rigorous exploration of the
      fundamental nature and maximal capabilities of this intriguing class of
      spintronic materials. We present the first study of size-dependence in granular
      magnetoresistance using colloidal nanoparticles. These data demonstrate a
      strongly nonlinear size-dependent magnetoresistance with smaller particles having
      strong DeltaR/R ~ 18% at 300 K and larger particles showing a 3-fold decline.
      Importantly, this indicates that CoFe2O4 can act as an effective room temperature
      granular magnetoresistor and that neither a high superparamagnetic blocking
      temperature nor a low overall resistance are determining factors in viable
      magnetoresistance values for sensing applications. These results demonstrate the
      promise of wider exploration of nontraditional granular structures composed of
      nanomaterials, molecule-based magnets, and metal-organic frameworks.

PMID- 30276257
TI  - On Demand Switching of Polymerization Mechanism and Monomer Selectivity with
      Orthogonal Stimuli.
AB  - The development of next-generation materials is coupled with the ability to
      predictably and precisely synthesize polymers with well-defined structures and
      architectures. In this regard, the discovery of synthetic strategies that allow
      on demand control over monomer connectivity during polymerization would provide
      access to complex structures in a modular fashion and remains a grand challenge
      in polymer chemistry. In this Article, we report a method where monomer
      selectivity is controlled during the polymerization by the application of two
      orthogonal stimuli. Specifically, we developed a cationic polymerization where
      polymer chain growth is controlled by a chemical stimulus and paired it with a
      compatible photocontrolled radical polymerization. By alternating the application
      of the chemical and photochemical stimuli the incorporation of vinyl ethers and
      acrylates could be dictated by switching between cationic and radical
      polymerization mechanisms, respectively. This enables the synthesis of multiblock
      copolymers where each block length is governed by the amount of time a stimulus
      is applied, and the quantity of blocks is determined by the number of times the
      two stimuli are toggled. This new method allows on demand control over polymer
      structure with external influences and highlights the potential for using stimuli
      controlled polymerizations to access novel materials.

PMID- 30276258
TI  - A Universal Descriptor for the Entropy of Adsorbed Molecules in Confined Spaces.
AB  - Confinement of hydrocarbons in nanoscale pockets and pores provides tunable
      capability for controlling molecules in catalysts, sorbents, and membranes for
      reaction and separation applications. While computation of the enthalpic
      interactions of hydrocarbons in confined spaces has improved, understanding and
      predicting the entropy of confined molecules remains a challenge. Here we show,
      using a set of nine aluminosilicate zeolite frameworks with broad variation in
      pore and cavity structure, that the entropy of adsorption can be predicted as a
      linear combination of rotational and translational entropy. The extent of entropy
      lost upon adsorption is predicted using only a single material descriptor, the
      occupiable volume (V occ). Predictive capability of confined molecular entropy
      permits an understanding of the relation with adsorption enthalpy, the ability to
      computationally screen microporous materials, and an understanding of the role of
      confinement on the kinetics of molecules in confined spaces.

PMID- 30276259
TI  - Iridium-Tungsten Alloy Nanodendrites as pH-Universal Water-Splitting
      Electrocatalysts.
AB  - The development of highly efficient and durable electrocatalysts for high
      performance overall water-splitting devices is crucial for clean energy
      conversion. However, the existing electrocatalysts still suffer from low
      catalytic efficiency, and need a large overpotential to drive the overall water
      splitting reactions. Herein, we report an iridium-tungsten alloy with
      nanodendritic structure (IrW ND) as a new class of high-performance and pH
      universal bifunctional electrocatalysts for hydrogen and oxygen evolution
      catalysis. The IrW ND catalyst presents a hydrogen generation rate ~2 times
      higher than that of the commercial Pt/C catalyst in both acid and alkaline media,
      which is among the most active hydrogen evolution reaction (HER) catalysts yet
      reported. The density functional theory (DFT) calculations reveal that the high
      HER intrinsic catalytic activity results from the suitable hydrogen and hydroxyl
      binding energies, which can accelerate the rate-determining step of the HER in
      acid and alkaline media. Moreover, the IrW NDs show superb oxygen evolution
      reaction (OER) activity and much improved stability over Ir. The theoretical
      calculation demonstrates that alloying Ir metal with W can stabilize the formed
      active iridium oxide during the OER process and lower the binding energy of
      reaction intermediates, thus improving the Ir corrosion resistance and OER
      kinetics. Furthermore, the overall water-splitting devices driven by IrW NDs can
      work in a wide pH range and achieve a current density of 10 mA cm-2 in acid
      electrolyte at a low potential of 1.48 V.

PMID- 30276260
TI  - Quantitative Analysis of Calcium Phosphate Nanocluster Growth Using Time-of
      Flight Medium-Energy-Ion-Scattering Spectroscopy.
AB  - One of the remaining challenges in material chemistry is to unveil the
      quantitative compositional/structural information and thermodynamic nature of
      inorganic materials especially in the initial nucleation and growth step. In this
      report, we adopted newly developed time-of-flight medium-energy-ion-scattering
      (TOF-MEIS) spectroscopy to address this challenge and explored heterogeneously
      grown nanometer-sized calcium phosphate as a model system. With TOF-MEIS, we
      discovered the existence of calcium-rich nanoclusters (Ca/P ~ 3) in the presence
      of the non-collagenous-protein-mimicking passivating ligands. Over the reaction,
      these clusters progressively changed their compositional ratio toward that of a
      bulk phase (Ca/P ~ 1.67) with a concurrent increase in their size to ~2 nm. First
      principles studies suggested that the calcium-rich nanoclusters can be stabilized
      through specific interactions between the ligands and clusters, emphasizing the
      important role of template on guiding the chemical and thermodynamic nature of
      inorganic materials at the nanoscale.

PMID- 30276261
TI  - Sodium-Ion Hybrid Capacitor of High Power and Energy Density.
AB  - Sodium-ion hybrid capacitors (NHCs) have been attracting research interest in
      recent years. However, NHCs suffer from slower redox reaction kinetics of
      electrodes as compared to non-Faradaic capacitive counterparts. Herein, a high
      performance NHC using porous NaBi as anode, activated carbon (AC) as cathode, and
      1.5 M of NaPF6 in diglyme as electrolyte is reported. In a charging process, Na+
      is inserted into NaBi to form Na3Bi, and PF6 - is stored in the electric double
      layers of the AC cathode; in a reverse process, the Na3Bi is desodiated to NaBi
      and eventually Bi, and the adsorbed PF6 - is released into the electrolyte in the
      first cycle. The NHC exhibits a capacity of ~298 mA h gBi -1, capacity retention
      of 98.6% after 1000 cycles at 2 A gBi -1, and Coulombic efficiency of >99.4%. The
      achievable power and energy density are as high as 11.1 kW kgtotal -1 and 106.5 W
      h kgtotal -1, respectively. The superior electrochemical performance is ascribed
      to the gradually formed three-dimensional (3D) porous and stable networks of the
      anode, ensuring its comparable fast reaction kinetics and cycle stability to the
      AC cathode.

PMID- 30276262
TI  - Structural and Biochemical Insights into the Function and Evolution of
      Sulfoquinovosidases.
AB  - An estimated 10 billion tonnes of sulfoquinovose (SQ) are produced and degraded
      each year. Prokaryotic sulfoglycolytic pathways catabolize sulfoquinovose (SQ)
      liberated from plant sulfolipid, or its delipidated form alpha-d-sulfoquinovosyl
      glycerol (SQGro), through the action of a sulfoquinovosidase (SQase), but little
      is known about the capacity of SQ glycosides to support growth. Structural
      studies of the first reported SQase (Escherichia coli YihQ) have identified three
      conserved residues that are essential for substrate recognition, but crossover
      mutations exploring active-site residues of predicted SQases from other organisms
      have yielded inactive mutants casting doubt on bioinformatic functional
      assignment. Here, we show that SQGro can support the growth of E. coli on par
      with d-glucose, and that the E. coli SQase prefers the naturally occurring
      diastereomer of SQGro. A predicted, but divergent, SQase from Agrobacterium
      tumefaciens proved to have highly specific activity toward SQ glycosides, and
      structural, mutagenic, and bioinformatic analyses revealed the molecular
      coevolution of catalytically important amino acid pairs directly involved in
      substrate recognition, as well as structurally important pairs distal to the
      active site. Understanding the defining features of SQases empowers bioinformatic
      approaches for mapping sulfur metabolism in diverse microbial communities and
      sheds light on this poorly understood arm of the biosulfur cycle.

PMID- 30276264
TI  - Evidence of a low-temperature dynamical transition in concentrated microgels.
AB  - A low-temperature dynamical transition has been reported in several proteins. We
      provide the first observation of a "protein-like" dynamical transition in
      nonbiological aqueous environments. To this aim, we exploit the popular colloidal
      system of poly-N-isopropylacrylamide (PNIPAM) microgels, extending their
      investigation to unprecedentedly high concentrations. Owing to the heterogeneous
      architecture of the microgels, water crystallization is avoided in concentrated
      samples, allowing us to monitor atomic dynamics at low temperatures. By elastic
      incoherent neutron scattering and molecular dynamics simulations, we find that a
      dynamical transition occurs at a temperature T d ~ 250 K, independently from
      PNIPAM mass fraction. However, the transition is smeared out on approaching dry
      conditions. The quantitative agreement between experiments and simulations
      provides evidence that the transition occurs simultaneously for PNIPAM and water
      dynamics. The similarity of these results with hydrated protein powders suggests
      that the dynamical transition is a generic feature in complex macromolecular
      systems, independently from their biological function.

PMID- 30276263
TI  - Structural and Mechanistic Insights into the Catalytic-Domain-Mediated Short
      Range Glycosylation Preferences of GalNAc-T4.
AB  - Mucin-type O-glycosylation is initiated by a family of polypeptide GalNAc
      transferases (GalNAc-Ts) which are type-II transmembrane proteins that contain
      Golgi luminal catalytic and lectin domains that are connected by a flexible
      linker. Several GalNAc-Ts, including GalNAc-T4, show both long-range and short
      range prior glycosylation specificity, governed by their lectin and catalytic
      domains, respectively. While the mechanism of the lectin-domain-dependent
      glycosylation is well-known, the molecular basis for the catalytic-domain
      dependent glycosylation of glycopeptides is unclear. Herein, we report the
      crystal structure of GalNAc-T4 bound to the diglycopeptide GAT*GAGAGAGT*TPGPG
      (containing two alpha-GalNAc glycosylated Thr (T*), the PXP motif and a "naked"
      Thr acceptor site) that describes its catalytic domain glycopeptide GalNAc
      binding site. Kinetic studies of wild-type and GalNAc binding site mutant enzymes
      show the lectin domain GalNAc binding activity dominates over the catalytic
      domain GalNAc binding activity and that these activities can be independently
      eliminated. Surprisingly, a flexible loop protruding from the lectin domain was
      found essential for the optimal activity of the catalytic domain. This work
      provides the first structural basis for the short-range glycosylation preferences
      of a GalNAc-T.

PMID- 30276265
TI  - Unprecedented high irreversibility line in the nontoxic cuprate superconductor
      (Cu,C)Ba2Ca3Cu4O11+delta.
AB  - One of the key factors that limit the high-power applications for a type II
      superconductor is the irreversibility line H irr(T), which reflects the very
      boundary of resistive dissipation in the phase diagram of magnetic field versus
      temperature. In cuprate family, the Y-, Bi-, Hg-, and Tl-based systems have
      superconducting transition temperatures exceeding the liquid nitrogen boiling
      temperature (~77 K). However, the toxic elements Hg and Tl in the latter two
      systems strongly constrain the applications. The best perspective so far is
      relying on the YBa2Cu3O7-delta (T c ~ 90 K) system, which is nontoxic and has a
      relatively high irreversibility magnetic field. We report the study of a nontoxic
      superconductor (Cu,C)Ba2Ca3Cu4O11+delta with T c = 116 K. We found that the
      irreversibility magnetic field is extremely high, and it thus provides great
      potential for applications above the liquid nitrogen temperature.

PMID- 30276266
TI  - Enhanced transport in transistor by tuning transition-metal oxide electronic
      states interfaced with diamond.
AB  - High electron affinity transition-metal oxides (TMOs) have gained a central role
      in two-dimensional (2D) electronics by enabling unprecedented surface charge
      doping efficiency in numerous exotic 2D solid-state semiconductors. Among them,
      diamond-based 2D electronics are entering a new era by using TMOs as surface
      acceptors instead of previous molecular-like unstable acceptors. Similarly,
      surface-doped diamond with TMOs has recently yielded record sheet hole
      concentrations (2 * 1014 cm-2) and launched the quest for its implementation in
      microelectronic devices. Regrettably, field-effect transistor operation based on
      this surface doping has been so far disappointing due to fundamental material
      obstacles such as (i) carrier scattering induced by nonhomogeneous morphology of
      TMO surface acceptor layer, (ii) stoichiometry changes caused by typical
      transistor fabrication process, and (iii) carrier transport loss due to
      electronic band energy misalignment. This work proposes and demonstrates a
      general strategy that synergistically surmounts these three barriers by
      developing an atomic layer deposition of a hydrogenated MoO3 layer as a novel
      efficient surface charge acceptor for transistors. It shows high surface
      uniformity, enhanced immunity to harsh fabrication conditions, and benefits from
      tunable electronic gap states for improving carrier transfer at interfaces. These
      breakthroughs permit crucial integration of TMO surface doping into transistor
      fabrication flows and allow outperforming electronic devices to be reached.

PMID- 30276268
TI  - Multidimensional spectroscopy with attosecond extreme ultraviolet and shaped near
      infrared pulses.
AB  - Dynamics following excitation with attosecond extreme ultraviolet (XUV) pulses
      arise from enormous numbers of accessible excited states, complicating the
      retrieval of state-specific time evolutions. We develop attosecond XUV
      multidimensional spectroscopy here to separate interfering pathways on a near
      infrared (NIR) energy axis, retrieving single state dynamics in argon atoms in a
      two-dimensional (2D) XUV-NIR spectrum. In this experiment, we measure four-wave
      mixing signal arising from the interaction of XUV attosecond pulses centered
      around 15 eV with two few-cycle NIR pulses. The 2D spectrum is created by
      measuring the emitted XUV signal field spectrum while applying narrowband
      amplitude and phase modulations to one of the NIR pulses. Application of such a
      technique to systems of high dimensionality will provide for the observation of
      state-resolved pure electronic dynamics, in direct analogy to phenomena unraveled
      by multidimensional spectroscopies at optical frequencies.

PMID- 30276267
TI  - An "ideal lignin" facilitates full biomass utilization.
AB  - Lignin, a major component of lignocellulosic biomass, is crucial to plant growth
      and development but is a major impediment to efficient biomass utilization in
      various processes. Valorizing lignin is increasingly realized as being essential.
      However, rapid condensation of lignin during acidic extraction leads to the
      formation of recalcitrant condensed units that, along with similar units and
      structural heterogeneity in native lignin, drastically limits product yield and
      selectivity. Catechyl lignin (C-lignin), which is essentially a benzodioxane
      homopolymer without condensed units, might represent an ideal lignin for
      valorization, as it circumvents these issues. We discovered that C-lignin is
      highly acid-resistant. Hydrogenolysis of C-lignin resulted in the cleavage of all
      benzodioxane structures to produce catechyl-type monomers in near-quantitative
      yield with a selectivity of 90% to a single monomer.

PMID- 30276269
TI  - Preoperative Needle Insertion Path Planning for Minimizing Deflection in
      Multilayered Tissues.
AB  - Fine needle deflection is a problem encountered during insertion into a soft
      tissue. Although an axial rotational insertion is an effective approach for
      minimizing this problem, needle deflection still depends on the insertion angle
      with respect to the tissue boundary. Since the human body consists of multi
      layered tissues of various shapes and mechanical properties, preoperative
      planning of an optimal path is a key factor for achieving a successful insertion.
      In this paper, we propose an optimization-based preoperative path planning model
      that minimizes needle deflection during multi-layered tissue insertion. This
      model can determine the optimal path based on the sum of insertion angles with
      respect to each tissue boundary that the needle passes through. To increase the
      accuracy of the model, we incorporated the effect of distances from tissue
      boundaries and the probability that the deflection is acceptable by incorporating
      weighting factors into the model. To validate the model, we performed experiments
      involving four scenarios of two- and three-layered tissues. The results showed
      that the proposed model is capable of determining the optimal insertion path in
      all scenarios.

PMID- 30276270
TI  - Le Fort Partial Colpocleisis: A Low-Cost Model.
AB  - Objective: The aim of this study is to develop a simulation model for the Le Fort
      partial colpocleisis. Introduction: One in 9 women will undergo surgery for
      incontinence or prolapse by age 80 with 30% of these requiring an additional
      prolapse surgery. With a success rate of over 90% and recurrence rate of 4.2%,
      obliterative procedures hold a significant place in the management of pelvic
      organ prolapse in elderly women who are no longer sexually active. For new
      trainees, the Le Fort colpocleisis may be difficult to conceptually visualize,
      requiring the need to develop models as teaching tools. Method: A low-cost model
      was developed using easily available craft supplies to simulate the Le Fort
      partial colpocleisis with the uterus in situ to treat procidentia. The cost of
      each model was under US $14 and time to make was approximately 1 hour. The video
      presents the construction and use of this model. Conclusions: The Le Fort partial
      colpocleisis technique has been in use for over a century. The aging population
      as well as the high risk of recurrence after prolapse repairs makes colpocleisis
      an important technique for trainees to master. Simulation models have proven
      their efficacy as a training tool. This simple model will allow trainees to fully
      comprehend the steps of this procedure. Using this video, educators can construct
      a model and use it to orient trainees to the Le Fort partial colpocleisis
      procedure.

PMID- 30276271
TI  - Amnion-derived stem cell transplantation: A novel treatment for neurological
      disorders.
AB  - In this review, we evaluated the literature reporting the use of amniotic stem
      cells (ASCs) in regenerative medicine for the treatment of neurological
      disorders. There is an increasing amount of evidence that indicates the
      exacerbation of the primary injury by inflammation in neurological disorders
      characterized by rampant inflammation, thereby increasing damage to the central
      nervous system (CNS). To address this, we focus on the amnion cells' anti
      inflammatory properties, which make their transplantation a promising treatment
      for these disorders. In addition, we offered insights into new applications of
      the ASC in the fields of regenerative medicine and tissue engineering.

PMID- 30276273
TI  - Effects of erythropoietin combined with tissue plasminogen activator on the rats
      following cerebral ischemia and reperfusion.
AB  - OBJECTIVES: Exogenously administered recombinant human erythropoietin (rhEPO) has
      been reported to exhibit neuroprotective effects in animal models. However, there
      are still have some controversies that combination of EPO and tissue plasminogen
      activator (tPA) in acute ischemic stroke. In the present study, we investigated
      the effects of local intra-arterial infusion of low-dose EPO in combination with
      tPA on focal cerebral ischemic stroke. MATERIALS AND METHODS: Sixty adult male
      Sprague-Dawley rats were randomly divided into five groups, including sham,
      vehicle, EPO, tPA, and EPO+tPA groups. Rats were subjected to middle cerebral
      artery occlusion (MCAO) and administrated with EPO (800 U/kg, middle cerebral
      artery injection), tPA (10 mg/kg, tail vein injection), EPO+tPA, or saline
      (vehicle) onset of reperfusion. Neurobehavioral deficits, infarct volume, brain
      edema, the expression of tight junction proteins (Claudin-5, Occludin), and AQP4
      were assessed following 2 h ischemia and 24 h reperfusion. The number of
      apoptotic cells in the periinfarct region was detected by the terminal
      deoxyribonucleotide transferase dUTP nick end labeling (TUNEL) staining. RESULTS:
      The neurobehavioral deficits, brain infarct volume, edema volume, TUNEL-positive
      cells and downregulation of Claudin-5 and Occludin were alleviated by EPO or EPO
      plus tPA, following the ischemia/reperfusion (I/R) in rats. The EPO and EPO plus
      tPA both reduced the upregulation of AQP4 in the ischemic brain tissue.
      CONCLUSION: Our data demonstrate local intra-arterial infusion of low-dose EPO in
      combination with tPA protected against focal cerebral ischemia in rats manifested
      by a decrease in brain edema and blood-brain barrier (BBB) disruption after 2 h
      ischemia and 24 h reperfusion.

PMID- 30276274
TI  - Pyruvate dehydrogenase complex in cerebral ischemia-reperfusion injury.
AB  - Pyruvate dehydrogenase (PDH) complex is a mitochondrial matrix enzyme that serves
      a critical role in the conversion of anaerobic to aerobic cerebral energy. The
      regulatory complexity of PDH, coupled with its significant influence in brain
      metabolism, underscores its susceptibility to, and significance in, ischemia
      reperfusion injury. Here, we evaluate proposed mechanisms of PDH-mediated
      neurodysfunction in stroke, including oxidative stress, altered regulatory
      enzymatic control, and loss of PDH activity. We also describe the neuroprotective
      influence of antioxidants, dichloroacetate, acetyl-L-carnitine, and combined
      therapy with ethanol and normobaric oxygen, explained in relation to PDH
      modulation. Our review highlights the significance of PDH impairment in stroke
      injury through an understanding of the mechanisms by which it is modulated, as
      well as an exploration of neuroprotective strategies available to limit its
      impairment.

PMID- 30276275
TI  - Rationale for ischemic conditioning to prevent stroke in patients with
      intracranial arterial stenosis.
AB  - Intracranial atherosclerotic arterial stenosis (ICAS) is one of the most common
      causes of stroke worldwide and is associated with particularly a high risk of
      recurrent stroke. Although aggressive medical management, consisting of dual
      antiplatelet therapy and intensive control of vascular risk factors, has improved
      the prognosis of patients with ICAS, subgroups of patients remain at very high
      risk of stroke. More effective therapies for these high-risk patients are
      urgently needed. One promising treatment is remote limb ischemic conditioning,
      which involves producing repetitive, transient ischemia of a limb by inflating a
      blood pressure cuff with the intention of protecting the brain from subsequent
      ischemia. In this study, we review the limitations of currently available
      treatments, discuss the potential mechanisms of action of ischemic conditioning,
      describe the preclinical and clinical data suggesting a possible role of ischemic
      conditioning in treating patients with ICAS, and outline the questions that still
      need to be answered in future studies of ischemic conditioning in subjects with
      ICAS.

PMID- 30276272
TI  - Biomarkers for acute diagnosis and management of stroke in neurointensive care
      units.
AB  - The effectiveness of current management of critically ill stroke patients depends
      on rapid assessment of the type of stroke, ischemic or hemorrhagic, and on a
      patient's general clinical status. Thrombolytic therapy with recombinant tissue
      plasminogen activator (r-tPA) is the only effective treatment for ischemic stroke
      approved by the Food and Drug Administration (FDA), whereas no treatment has been
      shown to be effective for hemorrhagic stroke. Furthermore, a narrow therapeutic
      window and fear of precipitating intracranial hemorrhage by administering r-tPA
      cause many clinicians to avoid using this treatment. Thus, rapid and objective
      assessments of stroke type at admission would increase the number of patients
      with ischemic stroke receiving r-tPA treatment and thereby, improve outcome for
      many additional stroke patients. Considerable literature suggests that brain
      specific protein biomarkers of glial [i.e. S100 calcium-binding protein B
      (S100B), glial fibrillary acidic protein (GFAP)] and neuronal cells [e.g.,
      ubiquitin C-terminal hydrolase-L1 (UCH-L1), neuron-specific enolase (NSE),
      alphaII-spectrin breakdown products SBDP120, SBDP145, and SBDP150, myelin basic
      protein (MBP), neurofilament light chain (NF-L), tau protein, visinin-like
      protein-1 (VLP 1), NR2 peptide] injury that could be detected in the
      cerebrospinal fluid (CSF) and peripheral blood might provide valuable and timely
      diagnostic information for stroke necessary to make prompt management and
      decisions, especially when the time of stroke onset cannot be determined. This
      information could include injury severity, prognosis of short-term and long-term
      outcomes, and discrimination of ischemic or hemorrhagic stroke. This chapter
      reviews the current status of the development of biomarker-based diagnosis of
      stroke and its potential application to improve stroke care.

PMID- 30276276
TI  - Wake-up stroke: Dawn of a new era.
AB  - Wake-up stroke or stroke with unclear onset of symptoms is known to occur in one
      fourth of ischemic stroke patients. These patients are not considered for
      thrombolytic therapy based on time designation of their symptom onset as per the
      current guidelines. Observational studies have investigated the pathophysiology
      and suggested actual onset of symptoms to be approximate to the awakening time
      for these patients. Use of advanced imaging modalities in these patients tends to
      identify favorable patient profiles for thrombolysis. Results of the ongoing
      trials will likely beckon a seminal juncture in stroke therapy and deliver
      critical modifications in the current treatment guidelines for thrombolysis in
      this substantial, yet neglected, group of stroke patients. In this article, we
      have reviewed the predisposing factors, preferred imaging modalities and various
      ongoing thrombolytic and endovascular trials to date for patients with unclear
      time of symptom onset or who wake up with stroke symptoms.

PMID- 30276277
TI  - Detrimental effects of physical inactivity on neurogenesis.
AB  - Patients diagnosed with neurological disorders exhibit a variety of physical and
      psychiatric symptoms, including muscle atrophy, general immobility, and
      depression. Patients who participate in physical rehabilitation at times show
      unexpected clinical improvement, which includes diminished depression and other
      stress-related behaviors. Regenerative medicine has advanced two major stem cell
      based therapies for central nervous system (CNS) disorders, transplantation of
      exogenous stem cells, and enhancing the endogenous neurogenesis. The latter
      therapy utilizes a natural method of re-innervating the injured brain, which may
      mend neurological impairments. In this study, we examine how inactivity-induced
      atrophy, using the hindlimb suspension model, alters neurogenesis in rats. The
      hypothesis is that inactivity inhibits neurogenesis by decreasing circulation
      growth or trophic factors, such as vascular endothelial growth or neurotrophic
      factors. The restriction modifies neurogenesis and stem cell differentiation in
      the CNS, the stem cell microenvironment is examined by the trophic and growth
      factors, including stress-related proteins. Despite growing evidence revealing
      the benefits of "increased" exercise on neurogenesis, the opposing theory
      involving "physical inactivity," which simulates pathological states, continues
      to be neglected. This novel theory will allow us to explore the effects on
      neurogenesis by an intransigent stem cell microenvironment likely generated by
      inactivity. 5-bromo-2-deoxyuridine labeling of proliferative cells, biochemical
      assays of serum, cerebrospinal fluid, and brain levels of trophic factors, growth
      factors, and stress-related proteins are suggested identifiers of neurogenesis,
      while evaluation of spontaneous movements will give insight into the psychomotor
      effects of inactivity. Investigations devised to show how in vivo stimulation, or
      lack thereof, affects the stem cell microenvironment are necessary to establish
      treatment methods to boost neurogenesis in bedridden patients.

PMID- 30276279
TI  - Clinical characteristics of 37 Chinese patients with myotonic dystrophy Type 1.
AB  - OBJECTIVE: This study aims to investigate clinical characteristics of 37 Chinese
      patients with Myotonic dystrophy Type 1 (DM1). METHODS: Main clinical features of
      these cases were analyzed, with a focus on multi-system involvements. RESULTS:
      The median age of onset was 21.5 years, with a range from 3 to 45 years. Fourteen
      patients had a family history positive for DM1, whereas the other 23 were
      sporadic cases. Twenty-seven of the patients were male. The primary symptoms were
      myotonia and weakness with varying multi-system involvement including cardiac
      defects, cataracts, sleep disturbances, cholecystopathy, and peripheral
      neuropathy. CONCLUSIONS: This is the first report in China with the diagnosis of
      DM1 decisively confirmed by CTG expansion testing. Data from our study suggest
      that Chinese DM1 cases have different clinical characteristics compared with
      those of Caucasian cases, especially the prevalence of cardiac defects,
      cataracts, and sleep disturbances.

PMID- 30276281
TI  - Erratum: The role of shear stress and arteriogenesis in maintaining vascular
      homeostasis and preventing cerebral atherosclerosis.
AB  - [This corrects the article on p. 53 in vol. 1.].

PMID- 30276278
TI  - Regeneration after stroke: Stem cell transplantation and trophic factors.
AB  - Stroke is a leading cause of death and disability worldwide. However, there is
      only one Food and Drug Administration-approved drug for the treatment of ischemic
      stroke, i.e., tissue plasminogen activator, and its therapeutic window is limited
      to within 4.5 h after stroke. Since clinical trials for neuroprotection have
      failed to demonstrate efficacy, multipotent and pluripotent stem cell
      transplantations are viable candidates for stroke treatment by providing trophic
      factor support and/or cell replacement following injury. The goal of this review
      is to highlight the promise of stem cell transplantation as vehicles for trophic
      factor delivery. The beneficial effects of different stem cell types as
      transplants as well as ways to upregulate trophic factors in stem cells are
      described in this review. Stem cell transplantation has consistently shown
      beneficial effects in the ischemic stroke model, in part due to the beneficial
      factors that stem cells release around the stroke injury area, resulting in
      smaller infarct volumes and regeneration and functional recovery. Upregulation of
      beneficial factors in stem cells and neural progenitors before transplantation
      has been shown to be even more effective in treating the stroke injury than stem
      cells without upregulated factors. However, for both stem cells and genetic
      engineering, there remain many unanswered questions and potential for
      improvement. These include modifiable parameters such as the different stem cell
      types and different factors, as well as the various readouts for investigation,
      such as various in vivo effects, such as immune system modulation and enhancement
      of endogenous neurogenesis and angiogenesis.

PMID- 30276280
TI  - A rare case report of bilateral internal carotid artery hypoplasia in postpartum
      female: Clinical spectrum and role of various modalities in diagnosis.
AB  - Congenital hypoplasia of bilateral internal carotid arteries (ICAs) is an
      extremely rare anomaly with less than 25 reported cases in literature till date.
      We present a case of a 30-year-old primigravida, who developed seizures and
      subsequently loss of consciousness just few minutes after the delivery of a
      healthy male child. To the best of our knowledge, this is the first case with
      bilateral ICA hypoplasia presenting in postpartum female who developed infarct in
      bilateral frontal region and subarachnoid hemorrhage (SAH). On a postpartum three
      dimensional (3D) computed tomography (CT) angiography, bilateral ICA hypoplasia
      was confirmed and the manifestations of infarcts were probably the consequence of
      altered hemodynamics of pregnancy. In conclusion, a patient in her late pregnancy
      and postpartum period, having nonspecific cerebral symptoms or having suffered a
      cerebrovascular accident, should not only be evaluated for pregnancy or
      puerperium-related complications but also whenever possible a baseline screening
      with Doppler study of neck vessels and a noncontrast magnetic resonance imaging
      (MRI) angiography of neck and cerebral vessels should be performed to rule out
      congenital anomalies.

PMID- 30276282
TI  - Current challenges in regenerative medicine for central nervous system disorders.

PMID- 30276284
TI  - Intra-arterial delivery of mesenchymal stem cells.
AB  - While treatments have been developed to combat stroke, such as intravenous
      recombinant tissue plasminogen activator and endovascular recanalization
      therapies, their ability to decrease the long-term disability that accompanies
      stroke is limited. Currently, stem cell research focused on mesenchymal stem
      cells (MSCs). MSCs are multipotent, nonhematopoietic stem cells found in the
      stromal fraction of the bone marrow, along with the connective tissue of most
      organs. MSCs are an increasingly appealing cell source due to the relative ease
      in which they can be retrieved, developed, and handled in vitro. Despite the fact
      that numerous paths of stem cell transport to the brain in acute ischemic stroke
      (AIS) exist, the intra-arterial (IA) route of stem cell transport is most
      attractive. This is due to its great potential for clinical translation,
      especially considering the growing clinical application of endovascular treatment
      for AIS. Here, we evaluate research examining IA delivery of MSCs to the stroke
      region. The results of the study revealed the maximum tolerated dose and that the
      optimal time for administration was 24 h, following cerebral ischemia. It is
      important that future translational studies are performed to establish IA
      administration of MSCs as a widely used treatment for AIS.

PMID- 30276283
TI  - Tracking mesenchymal stem cells using magnetic resonance imaging.
AB  - Recent translational studies in the fields of tissue regeneration and cell
      therapy have characterized mesenchymal stem cells (MSCs) as a potentially
      effective and accessible measure for treating ischemic cerebral and
      neurodegenerative disorders such as stroke, Parkinson's disease, and amyotrophic
      lateral sclerosis. Developing more efficient cell tracking techniques bear the
      potential to optimize MSC transplantation therapies by providing a more accurate
      picture of the fate and area of effect of implanted cells. Currently, determining
      the location of transplanted MSCs involves a histological approach, but magnetic
      resonance imaging (MRI) presents a noninvasive paradigm that permits repeat
      evaluations. To visualize MSCs using MRI, the implanted cells must be treated
      with an intracellular contrast agent. These are commonly paramagnetic compounds,
      many of which are based on superparamagnetic iron oxide (SPIO) nanoparticles.
      Recent research has set out characterize the effects of SPIO-uptake on the
      cellular activity of in vitro human MSCs and the resultant influence that
      respective SPIO concentration has on MRI sensitivity. As these studies reveal,
      SPIO-uptake has no effect on the cellular processes of proliferation and
      differentiation while producing high contrast MRI signals. Moreover,
      transplantation of SPIO-labeled MSCs in animal models encouragingly showed no
      loss in MRI contrast, suggesting that SPIO labeling may be an appealing regime
      for lasting MRI detection. This study is a review article. Referred literature in
      this study has been listed in the reference part. The datasets supporting the
      conclusions of this article are available online by searching the PubMed. Some
      original points in this article come from the laboratory practice in our research
      centers and the authors' experiences.

PMID- 30276285
TI  - Reducing excitoxicity with glutamate transporter-1 to treat stroke.
AB  - The neurotransmitter glutamate is released following ischemic brain damage, and
      its excitotoxic effects contribute greatly to the development of stroke. Because
      this release of glutamate occurs within minutes, therapeutic drugs targeting the
      restriction of glutamate-induced excitotoxicity must be administered quickly
      following ischemic onset. Here, we evaluate an alternative research approach
      examining the overexpression of glutamate transporter 1 (GLT1) to reduce
      infarction and improve behavioral deficits induced by stroke in a rat model of
      stroke. Recent studies verify the role of glutamate overflow in the pathogenesis
      of stroke. The experimental approach evaluated glutamate clearance, following
      ischemia-induced overflow where the GLT had been genetically manipulated to be
      overexpressed in the ischemic region. A viral vector-mediated gene transfer
      approach activated the overexpression of GLT1 to successfully reduce ischemia
      induced glutamate overflow, decrease cell death, and improve behavioral recovery
      among animal models. These findings further support the role of glutamate in the
      pathogenesis of stroke and the upregulation of endogenous GLT1 as a promising
      approach to protect against the effects of ischemic brain damage caused by
      glutamate excitotoxicity. This study is a review article. Referred literature in
      this paper has been listed in the references part. The datasets supporting the
      conclusions of this article are available online by searching the PubMed. Some
      original points in this article come from the laboratory practice in our research
      centers and our experiences.

PMID- 30276286
TI  - Clinical application of oligodendrocyte precursor cells for cell-based therapy.
AB  - Oligodendrocyte precursor cells (OPCs), which give rise to mature
      oligodendrocytes (OLs), play important roles in maintaining white matter
      function. Even during the adulthood period, OPCs comprise roughly 5% of all cells
      in the forebrain and retain a capability to become myelinated OLs. Recently, OPCs
      have been proposed as a novel source for cell-based therapy. For the purpose,
      OPCs can be obtained from embryonic stem cells, induced pluripotent stem cells,
      and directly converted cells derived from patients. Here, we will provide a brief
      review of the potential of using OPCs as a cell-based therapy for treating
      various neurological diseases.

PMID- 30276287
TI  - A polarizing view on posttraumatic brain injury inflammatory response.
AB  - Traumatic brain injury (TBI) activates the simultaneous proliferation of various
      pro- and anti-inflammatory molecules. Considering the amount of factors
      participating, this response is naturally complex. However, there is an
      increasing trend in neurotrauma research to delineate the injury-induced
      inflammatory responses within the constraints of in vitro defined macrophage
      polarization phenotypes "M1" and "M2". Here, we evaluate research examining the
      complexity of the inflammatory response that cannot be so easily characterized
      using this binary nomenclature. TBI is demonstrated to induce a broad spectrum of
      simultaneous expression responses involving both pro- and anti-inflammatory
      reactions. Specifically, the research revealed a very heterogeneous parenchymal
      landscape associated with TBI. The concurrent expression of both "M1" and "M2"
      phenotypic markers on the microglia/macrophages involved suggests that the
      polarization phenotypes cannot be neatly defined in this M1/M2 paradigm. Recent
      studies displaying neurotrauma also report similar conflict with the constraints
      of this binary categorization of "M1/M2", demonstrating that
      microglia/macrophages cannot effectively cross-over to strictly polarized "M1
      only" or "M2-only" phenotype. Therefore, the complex signaling events surrounding
      this response indicate that a binary M1/M2 characterization is not adequate to
      define inflammatory profile. This paper is a review article. Referred literature
      in this paper has been listed in the references part. The datasets supporting the
      conclusions of this article are available online by searching the PubMed. Some
      original points in this article come from the laboratory practice in our research
      centers and the authors' experiences.

PMID- 30276288
TI  - Finding effective biomarkers for pediatric traumatic brain injury.
AB  - As traumatic brain injury (TBI) continues to affect children and young adults
      worldwide, research on reliable biomarkers grows as a possible aid in determining
      the severity of injury. However, many studies have revealed that diverse
      biomarkers such as S100B and myelin basic protein (MBP) have many limitations,
      such as their elevated normative concentrations in young children. Therefore, the
      results of these studies have yet to be translated to clinical applications.
      However, despite the setbacks of research into S100B and MBP, investigators
      continue to research viable biomarkers, notably glial fibrillary acidic protein
      (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1), as possible aids in
      medical decision making. Studies have revealed that GFAP and UCH-L1 actually are
      better predictors of injury progression than the before-mentioned biomarkers
      S100B and MBP. In addition, UCH-L1 has demonstrated an ability to detect injury
      while CT is negative, suggesting an ability to detect acute intracranial lesions.
      Here, we evaluate research testing levels of GFAP and UCH-L1 on children
      diagnosed with TBI and compare our results to those of other tested biomarkers.
      In a recent study done by Hayes et al., GFAP and UCH-L1 demonstrated the
      potential to recognize children with the possibility of poor outcome, allowing
      for more specialized treatments with clinical and laboratory applications.
      Although studies on GFAP and UCH-L1 have for the most part warranted positive
      results, further studies will be needed to confirm their role as reliable markers
      for pediatric TBI.

PMID- 30276289
TI  - Creatine supplementation improves neural progenitor cell survival in Huntington's
      disease.
AB  - Preclinical and clinical studies suggest that striatal transplantation of neural
      stem cells (NSCs) and neural progenitor cells (NPCs) may be an appealing and
      valuable system for treating Huntington's disease. Nevertheless, for a neural
      replacement to become an effective translational treatment for Huntington's
      disease, a certain number of difficulties must be addressed, including how to
      improve the integration of transplanted cell grafts with the host tissue, to
      elevate the survival rates of transplanted cells, and to ensure their directed
      differentiation into specific neuronal phenotypes. Research focusing on the
      translational applications of creatine (Cr) supplementation in NSC and NPC cell
      replacement therapies continues to offer promising results, pointing to Cr as a
      factor with the potential to improve cell graft survivability and encourage
      differentiation toward GABAergic phenotypes in models of striatal
      transplantation. Here, we evaluate research examining the outcomes of Cr
      supplementation and how the timing of supplementation regimes may affect their
      efficacy. The recent studies indicate that Cr's effects vary according to the
      developmental stage of the cells being treated, noting the dynamic differences in
      creatine kinase expression over the developmental stages of differentiating NPCs.
      This research continues to move Cr supplementation closer to the widespread
      clinical application and suggests such techniques warrant further examination.

PMID- 30276290
TI  - A therapeutic shock propels Schwann cells to proliferate in peripheral nerve
      injury.
AB  - Damage to the peripheral nervous system (PNS) is a prevalent issue and represents
      a great burden to patients. Although the PNS has a good capacity for
      regeneration, regeneration over long distances poses several difficulties.
      Several recent studies have addressed Schwann cells' limited proliferative
      capacity; however, a solution has yet to be found. Here, we examine the effects
      of extracorporeal shock wave therapy (ESWT) on Schwann cell isolation, culture,
      and proliferation rate. The study conducted demonstrated that Schwann cells
      treated with ESWT had significantly improved isolation, culture, and
      proliferative capacities. These findings represent a solution to a significant
      problem that hospitals and health-care providers face every year: how to treat
      long distance damage to the PNS with the limited proliferative capabilities of
      Schwann cells. Although these findings are promising, further studies must be
      conducted to address the molecular mechanisms by which ESWT alters Schwann cells
      and the potential implications for peripheral nerve damage and other prevalent
      illnesses. This study is a review article. Referred literature in this paper has
      been listed in the references part. The datasets supporting the conclusions of
      this article are available online by searching the PubMed. Some original points
      in this article come from the laboratory practice in our research centers and the
      authors' experiences.

PMID- 30276291
TI  - Nonhuman primate model in clinical modeling of diseases for stem cell therapy.
AB  - Nonhuman primates (NHPs) are alike humans in size, behavior, physiology,
      biochemistry, and immunology. Given close similarities to humans, the NHP model
      offers exceptional opportunities to understand the biological mechanisms and
      translational applications with direct relevance to human conditions. Here, we
      evaluate the opportunities and limitations of NHPs as animal models for
      translational regenerative medicine. NHP models of human disease propose
      exceptional opportunities to advance stem cell-based therapy by addressing
      pertinent translational concerns related to this research. Nonetheless, the value
      of these primates must be carefully assessed, taking into account the expense of
      specialized equipment and requirement of highly specialized staff. Well-designed
      initial fundamental studies in small animal models are essential before
      translating research into NHP models and eventually into human trials. In
      addition, we suggest that applying a directed and collaborative approach, as seen
      in the evolution of stroke NHP models, will greatly benefit the translation of
      stem cell therapy in other NHP disease models.

PMID- 30276292
TI  - Science, ethics and communication remain essential for the success of cell-based
      therapies.
AB  - Cell-based therapeutics, such as marrow or peripheral blood stem cell
      transplantation, are a standard of care for certain malignancies. More recently,
      a wider variety of cell-based therapeutics including the use of mesenchymal
      stromal/stem cells, T-cells, and others show great promise in a wider range of
      diseases. With increased efforts to expand cell-based treatments to several
      clinical settings, many institutions around the world have developed programs to
      explore cellular therapy's potential for safe and effective applications. In
      legitimate investigations, usually conducted through academic centers or
      biotechnology industry-sponsored efforts, these studies are regulated and peer
      reviewed to ensure safety and clear determination of potential efficacy. However,
      in some cases, the use of cell-based approaches is conducted with insufficient
      preclinical data, scientific rationale, and/or study plan for the diseases
      claimed to be treated, with patients being charged for these services without
      clear evidence of clinical benefit. In this context, patients may not be properly
      informed regarding the exact treatment they are receiving within a consenting
      process that may not be completely valid or ethical. Here, the authors emphasize
      the importance of distinguishing "proven cell-based therapies" from "unproven"
      and unauthorized cell-based therapies. This publication also addresses the
      necessity for improved communication between the different stakeholders in the
      field, patient associations, and advocacy groups in particular, to favor medical
      innovation and provide legitimate benefits to patients. Considering the
      progressive growth of cell-based treatments, their increasing therapeutic value
      and the expectation that society has about these therapies, it is critically
      important to protect patients and ensure that the risk/benefit ratio is
      favorable. This paper is a review article. Literature referred to in this paper
      has been listed in the references section. The datasets supporting the
      conclusions of this article are available online by searching PubMed. Some
      original points in this article come from the laboratory practice in our research
      centers and the authors' experiences.

PMID- 30276295
TI  - Endovascular therapy for acute ischemic stroke: The standard of care.
AB  - Acute ischemic stroke continues to be a major cause of permanent disability and
      death worldwide. Outcomes are particularly poor in patients presenting with large
      vessel occlusive disease with resultant ischemia and tissue injury in large and
      eloquent territories. Intravenous thrombolysis has been the mainstay of medical
      therapy, however treatment is limited to a subset of patients and many patients
      continue to have poor outcomes. Three trials in 2013 investigating the benefit of
      intra-arterial therapy failed to demonstrate benefit over medical therapy alone.
      More recently, five trials in 2015 were completed demonstrating superior outcomes
      with intra-arterial therapy with improved results attributed to higher and faster
      rates of recanalization in a select patient population. These trials have
      introduced a new standard of care in the management of acute ischemic stroke
      patients.

PMID- 30276294
TI  - Facial nerve stimulation as a future treatment for ischemic stroke.
AB  - Stimulation of the autonomic parasympathetic fibers of the facial nerve system
      (hereafter simply "facial nerve") rapidly dilates the cerebral arteries and
      increases cerebral blood flow whether that stimulation is delivered at the facial
      nerve trunk or at distal points such as the sphenopalatine ganglion. Facial nerve
      stimulation thus could be used as an emergency treatment of conditions of brain
      ischemia such as ischemic stroke. A rich history of scientific research has
      examined this property of the facial nerve, and various means of activating the
      facial nerve can be employed including noninvasive means. Herein, we review the
      anatomical and physiological research behind facial nerve stimulation and the
      facial nerve stimulation devices that are in development for the treatment of
      ischemic stroke.

PMID- 30276296
TI  - Region-specific disruption of synapsin phosphorylation following ethanol
      administration in brain-injured mice.
AB  - Introduction: Civilians and military personnel develop a range of physical and
      psychosocial impairments following traumatic brain injury (TBI), including
      alcohol abuse. As a consequence, increased rates of alcohol misuse magnify TBI
      induced pathologies and impede rehabilitation efforts. Therefore, a developed
      understanding of the mechanisms that foster susceptibility of the injured brain
      to alcohol sensitivity and the response of the injured brain to alcohol is
      imperative for the treatment of TBI patients. Alcohol sensitivity has been
      demonstrated to be increased following experimental TBI and, in additional
      studies, regulated by presynaptic vesicle release mechanisms, including synapsin
      phosphorylation. Materials and Methods: Mice were exposed to controlled midline
      impact of the intact skull and assessed for cortical, hippocampal, and striatal
      expression of phosphorylated synapsin I and II in response to high-dose ethanol
      exposure administered 14 days following injury, a time point at which injured
      mice demonstrate increased sedation after ethanol exposure. Results and
      Discussion: Immunoblot quantitation revealed that TBI alone, compared to sham
      controls, significantly increased phosphorylated synapsin I and II protein
      expression in the striatum. In sham controls, ethanol administration
      significantly increased phosphorylated synapsin I and II protein expression
      compared to saline-treated sham controls; however, no significant increase in
      ethanol-induced phosphorylated synapsin I and II protein expression was observed
      in the striatum of injured mice compared to saline-treated TBI controls. A
      similar expression pattern was observed in the cortex although restricted to
      increases in phosphorylated synapsin II. Conclusion: These data show that
      increased phosphorylated synapsin expression in the injured striatum may reflect
      a compensatory neuroplastic response to TBI which is proposed to occur as a
      result of a compromised presynaptic response of the injured brain to high-dose
      ethanol. These results offer a mechanistic basis for the altered ethanol
      sensitivity observed following experimental TBI and contribute to our
      understanding of alcohol action in the injured brain.

PMID- 30276297
TI  - beta4 integrin is not essential for localization of hemidesmosome proteins
      plectin and CD151 in cerebral vessels.
AB  - Objective: In the central nervous system (CNS), beta4 integrin is predominantly
      expressed by endothelial cells lining arterioles. As beta4 integrin plays an
      essential role in epithelial tissues, organizing structural proteins into
      specialized adhesive structures called hemidesmosomes (HD), the aim of this study
      was to determine whether it plays a similar role in CNS endothelium. Methods:
      Dual-immunofluorescence was used to examine the relationship between beta4
      integrin expression and co-expression of the HD proteins plectin and CD151 in
      frozen sections of mouse brain, both under normoxic (control) conditions and
      following chronic mild hypoxia. The requirement of beta4 integrin for the
      localization of HD proteins was examined in transgenic mice lacking beta4
      integrin expression specifically in endothelial cells (beta4-EC-KO mice).
      Results: Immunofluorescence revealed that in the normal adult CNS, plectin and
      CD151 strongly co-localized with beta4 integrin in arterioles. However, in the
      chronic mild hypoxia model, in which extensive cerebrovascular remodeling is
      observed, plectin and CD151 were strongly upregulated on all cerebral vessels,
      but surprisingly, in capillaries, this occurred in a beta4 integrin-independent
      manner. Unexpectedly, absence of endothelial beta4 integrin (in beta4-EC-KO mice)
      had no impact on the expression level or distribution pattern of plectin and
      CD151 within stable or remodeling cerebral vessels. Conclusions: These results
      demonstrate that the HD proteins plectin and CD151 are closely associated with
      beta4 integrin on arterioles in normal brain, and are strongly upregulated on
      remodeling blood vessels. However, unlike its described role in the epidermis,
      beta4 integrin is not essential for localization or regulation of expression of
      plectin and CD151 in cerebral vessels.

PMID- 30276293
TI  - Targeting oxidative stress for the treatment of ischemic stroke: Upstream and
      downstream therapeutic strategies.
AB  - Excessive oxygen and its chemical derivatives, namely reactive oxygen species
      (ROS), produce oxidative stress that has been known to lead to cell injury in
      ischemic stroke. ROS can damage macromolecules such as proteins and lipids and
      leads to cell autophagy, apoptosis, and necrosis to the cells. This review
      describes studies on the generation of ROS, its role in the pathogenesis of
      ischemic stroke, and recent development in therapeutic strategies in reducing
      oxidative stress after ischemic stroke.

PMID- 30276299
TI  - Activated complement protein C5a does not affect brain-derived endothelial cell
      viability and zonula occludens-1 levels following oxygen-glucose deprivation.
AB  - BACKGROUND AND PURPOSE: Ischemic brain injury induces both functional and
      structural disarray affecting the blood-brain barrier (BBB) which in return
      aggravates stroke outcomes. Complement system and its bioactive proteins are
      important molecular responders to ischemia. C5a protein along with its receptor
      C5a receptor 1 is a key component of this system with potent pro-inflammatory and
      chemoattractant properties. The purpose of this study is to investigate the role
      of C5a protein and its receptor which are believed to participate in the
      inflammatory response that follows ischemic insult. MATERIALS AND METHODS: To
      mimic an ischemic in vivo event in which C5a may contact brain endothelial cells
      after injury, we studied oxygen-glucose deprivation (OGD) followed by reperfusion
      in brain microvascular endothelial cells (b.End. 3) by only added C5a at the time
      of reperfusion. Cell death and viability were estimated by trypan blue and 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, respectively. Tight
      junction protein zonula occluden (ZO-1) levels were analyzed by Western blot
      analysis, and nitric oxide (NO) was assessed using the Griess reagent. RESULTS:
      Brain-derived endothelial cell was susceptible to OGD-induced injury in a
      duration-dependent manner as was the presence of ZO-1 protein. However, the
      addition of C5a protein had no notable effects even when used at high
      concentrations up to 100 nM. While OGD led to reduction in ZO-1 protein levels,
      no change was seen following the addition of C5a. Finally, OGD led unexpectedly
      to small decreases in NO generation, but this was again unaltered by C5a.
      CONCLUSIONS: Our study suggests that complement system protein C5a may not have a
      direct role in the disruption of BBB, following brain ischemia. This is in
      contrary with previous literature that suggests a possible role of this protein
      in the inflammatory response to ischemia.

PMID- 30276300
TI  - MicroRNA-99a-5p in circulating immune cells as a potential biomarker for the
      early diagnosis of ischemic stroke.
AB  - OBJECTIVES: We have previously shown the neuroprotective function of microRNA-99a
      5p in experimental stroke. Here, we explore its diagnostic potential for acute
      stroke patients. MATERIALS AND METHODS: MiR-99a-5p levels in circulating from
      acute stroke patients and control were measured by real-time polymerase chain
      reaction. Pearson's correlation and receiver operator characteristic (ROC) curves
      were used to analyze clinical significance of miR-99a-5p and its sensitivity and
      specificity for stroke diagnosis. RESULTS: We demonstrated that miR-99a-5p
      expression was upregulated in neutrophils of both ischemic stroke and hemorrhage
      patients, while was only increased in the lymphocytes of hemorrhage patients. ROC
      analysis revealed that the miR-99a-5p level in neutrophils and lymphocytes had a
      moderate diagnostic value for stroke. Moreover, a positive correlation existed
      between plasma miR-99a-5p levels and neutrophil numbers or neutrophil/lymphocyte
      ratio. Meanwhile, miR-99a-5p levels in neutrophils were negatively correlated
      with thrombin time, while positively correlated with D-dimer and urea levels.
      Lymphocytic miR-99a-5p levels were positively correlated with platelet mean
      volume and distribution width. CONCLUSION: This study demonstrated that miR-99a
      5p levels in circulating immune cells might facilitate the diagnosis of ischemic
      stroke.

PMID- 30276303
TI  - Erratum: Facial nerve stimulation as a future treatment for ischemic stroke.
AB  - [This corrects the article on p. 164 in vol. 2.].

PMID- 30276302
TI  - Nonalcoholic fatty liver disease as an independent risk factor for carotid
      atherosclerosis.
AB  - PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is a frequently encountered
      clinical condition in clinical practice, particularly in obese and diabetic
      patients. Carotid atherosclerosis is regarded as surrogate marker of coronary
      atherosclerosis. We aimed to know whether evaluation for carotid atherosclerosis
      should be done in all patients of NAFLD. MATERIALS AND METHODS: A total of 200
      NAFLD patients and 100 age- and sex-matched controls were enrolled into the
      study. Ultrasound was done to document fatty liver and carotid intimal thickness,
      and relation between these two was observed. RESULTS: Grade 1 fatty liver was
      seen in 36% patients while Grade 2 fatty liver was found in 39% and Grade 3 fatty
      liver in 25%. Patients with Grade 1 fatty liver had left intima-media thickness
      (IMT) in the range of 0.4-0.6 mm (mean IMT - 0.69 mm) and had right IMT in the
      range of 0.5-0.8 mm (mean IMT - 0.71 mm). In patients with Grade 2 fatty liver,
      left IMT was in the range of 0.6-1.0 mm (mean IMT - 0.80 mm) and right IMT in the
      range of 0.7-1.0 mm (mean IMT - 0.84 mm), while in patients with Grade 3 fatty
      liver, left IMT was in the range of 0.8-1.2 mm (mean IMT - 0.93 mm) and right IMT
      in the range of 0.9-1.4 mm (mean IMT - 0.99 mm). Among controls, the mean left
      IMT was 0.579 mm and mean right IMT was 0.575 mm. CONCLUSION: The level of
      carotid intimomedial thickness was more in cases than in controls and
      progressively increased with the grade of fatty liver which was statistically
      significant.

PMID- 30276298
TI  - The role of hormesis in the functional performance and protection of neural
      systems.
AB  - This paper addresses how hormesis, a biphasic dose response, can protect and
      affect performance of neural systems. Particular attention is directed to the
      potential role of hormesis in mitigating age-related neurodegenerative diseases,
      genetically based neurological diseases, as well as stroke, traumatic brain
      injury, seizure, and stress-related conditions. The hormetic dose response is of
      particular significance since it mediates the magnitude and range of
      neuroprotective processes. Consideration of hormetic dose-response concepts can
      also enhance the quality of study designs, including sample size/statistical
      power strategies, selection of treatment groups, dose spacing, and
      temporal/repeat measures' features.

PMID- 30276301
TI  - Mortality in ischemic stroke score: A predictive score of mortality for acute
      ischemic stroke.
AB  - OBJECTIVE: This prospective study was planned to formulate and evaluate a
      predictive score for in-hospital mortality in cases of acute ischemic stroke.
      MATERIALS AND METHODS: In this study, 188 consecutive patients of ischemic stroke
      were included over 19 months. Only patients with renal failure and malignancy
      were excluded from the study. All patients were subjected to clinical evaluation
      along with Glasgow Coma Scale (GCS), National Institute of Health Science scale
      (NIHSS) score, and modified Rankin score (mRS). Investigations total leukocyte
      count (TLC), capillary blood sugar at admission, high-sensitivity C-reactive
      protein (HS-CRP), and troponin I, electrocardiogram, and neuroimaging were
      performed. The patients were followed up till their outcome in the hospital, and
      patients who expired were grouped as "mortality group" and the rest as
      "discharged group." One-way anova analysis was carried out among the significant
      parameters to identify independent predictors of mortality in cases of ischemic
      stroke. RESULTS: After statistical analysis, it was found that late presentation
      to the hospital, pyrexia (temperature >99F), low diastolic blood pressure at the
      time of admission, hypoxia (saturation of oxygen <94%), NIHSS score >15, mRS >3,
      GCS <8, hyperglycemia (random blood sugar >200 mg/dL), raised TLC, and HS-CRP
      (>10 mg/L) are positive predictive factors of mortality in cases of ischemic
      stroke. Based on the above findings, a simple and easily applicable mortality in
      ischemic stroke (MIS) score is developed. CONCLUSION: This MIS score system will
      help the clinicians in better management of the patient and improved counseling
      the relatives of patients with ischemic stroke.

PMID- 30276304
TI  - The cerebral circulation: The centrality of its function, the catastrophe of its
      failure.

PMID- 30276305
TI  - The cerebral circulation and cerebrovascular disease I: Anatomy.
AB  - In this paper, which is the first in a three-part series that reviews
      cerebrovascular anatomy, pathogenesis, and stroke, we lay the anatomical
      foundation for the rest of the series. Beginning with its origin in the branches
      of the aorta, we start by describing the arterial system. This system is
      partitioned into two major divisions (anterior and posterior circulations) that
      differ significantly in features and pathogenic potential. The systems, and the
      major branches that comprise them, are described. Description of the arterial
      system proceeds to the point of the fulfillment of its function. This function,
      the exchange of gases and nutrients with the cerebral parenchyma, is the subject
      of a subsequent section on the microcirculation and blood-brain barrier. Finally,
      the cerebral venous system, which is composed of cerebral veins and dural venous
      sinuses, is described. Thus, an anatomical context is supplied for the discussion
      of cerebrovascular disease pathogenesis provided by our second paper.

PMID- 30276306
TI  - The cerebral circulation and cerebrovascular disease II: Pathogenesis of
      cerebrovascular disease.
AB  - In this paper, we review the cerebral circulation and cerebrovascular disease
      (CVD) with an overview of the major types of CVD pathogenesis. These, as
      categorized here, are as follows: occlusive injury intrinsic to blood vessels,
      occlusive injury extrinsic to blood vessels, cerebral hypoperfusion, and cerebral
      hemorrhage. Following an overview of each of these categories, we conclude with a
      discussion of cerebral edema to illustrate how the pathological origins we
      covered can progress clinically. The content of this paper sets the stage for the
      detailed, clinically oriented discussion of stroke with which our series
      culminates in its subsequent Part III.

PMID- 30276307
TI  - The cerebral circulation and cerebrovascular disease III: Stroke.
AB  - In this paper, our review series on cerebrovascular disease anatomy, physiology,
      and pathology ends with a thorough discussion of the most significant
      cerebrovascular pathology: stroke. This discussion proceeds through two layers of
      organization. First, stroke is divided up into its main etiologic categories
      (ischemic stroke/transient ischemic attack, hemorrhagic stroke, and ischemic to
      hemorrhagic transformation). Then, the epidemiological, pathophysiological,
      clinical, and therapeutic (employed currently as well as emerging) aspects of
      each etiology are explored; emphasis is placed upon the therapeutic aspects.
      Finally, once we have covered all aspects of each etiologic category, we end our
      review with a defense of the thesis that there is much hope for the future of
      stroke treatment to be derived from familiarity with the literature on emerging
      therapies.

PMID- 30276308
TI  - Tackling issues in the path toward clinical translation in brain conditioning:
      Potential offered by nutraceuticals.
AB  - Brief periods of ischemia have been shown in many experimental setups to provide
      tolerance against ischemia in multiple organs including the brain, when
      administered before (preconditioning) or even after (postconditioning) the
      normally lethal ischemia. In addition to these so-called ischemic conditionings,
      many pharmacological and natural agents (e.g., chemicals and nutraceuticals) can
      also act as potent pre- and post-conditioners. Deriving from the original concept
      of ischemic preconditioning, these various conditioning paradigms may be
      promising as clinical-stage therapies for prevention of ischemic-related injury,
      especially stroke. As no proven experimentally identified strategy has translated
      into clinical success, the experimental induction of neuroprotection using these
      various conditioning paradigms has raised several questions, even before
      considering translation to clinical studies in humans. The first aim of the
      review is to consider key questions on preclinical studies of pre- or post
      conditioning modalities including those induced by chemical or nutraceuticals.
      Second, we make the argument that several key issues can be addressed by a novel
      concept, nutraceutical preconditioning. Specifically, alpha-linolenic acid (alpha
      linolenic acid [ALA] an omega-3 polyunsaturated fatty acid), contained in plant
      derived edible products, is essential in the daily diet, and a body of work has
      identified ALA as a pre- and post-conditioner of the brain. Nutritional
      intervention and functional food development are an emerging direction for
      preventing stroke damage, offering the potential to improving clinical outcomes
      through activation of the endogenous protective mechanisms known collectively as
      conditioning.

PMID- 30276311
TI  - Doppler sonographic assessment of carotid arteries in Sudanese stroke patients.
AB  - BACKGROUND: Hypertension, diabetes, and smoking were considered to be associated
      with several public health problems. OBJECTIVE: the study aims to explore the
      hemodynamic of carotid arteries in association with hypertension, diabetes, and
      smoking in Sudanese stroke patients. MATERIALS AND METHODS: In a quantitative
      descriptive study, fifty patients with stroke were scanned by B-mode and Doppler
      sonography. Carotid arteries were investigated with a 7-MHz linear transducer by
      a standard carotid sonography protocol. RESULTS: The average Doppler resistive
      index (RI) was 0.71 +/- 0.084 and intima-media thickness was 1.39 +/- 0.78 mm.
      The end diastolic velocities (EDVs) and peak systolic velocities (PSVs) of common
      carotid arteries were significantly changed in smokers and hypertensive (P <
      0.05). The elevation of RI in right and left CCAs were significantly correlated
      with smokers (P = 0.017 and 0.010 respectively). Hemorrhagic stroke was most
      prevalent in hypertensive rather than diabetic and smokers. The carotid
      hemodynamics changed significantly in hypertensive and smokers more than
      diabetics. CONCLUSION: EDV and PSV were significantly correlated with
      hypertension and tobacco smoking rather than diabetes. Hypertension, diabetes,
      and smoking have an association with stroke and hand significant effect on
      carotid artery hemodynamic and atherosclerotic disease. The Doppler RIs were
      significantly correlated with smokers. Patients with risk factors of stroke
      should be scanned with Doppler sonography as early as possible.

PMID- 30276312
TI  - Recent progress in regenerative medicine for brain disorders.

PMID- 30276310
TI  - Targeting G protein-coupled receptor for pain management.
AB  - Pain is an unpleasant sensory and emotional experience associated with actual or
      potential tissue damage or described in terms of such damage. Great progress has
      been made in understanding the important roles of various G protein-coupled
      receptors in the regulation of pain transmission. However, many important
      questions remain uncertain about the precise signal transduction mechanisms. This
      review focuses opioid receptor and CXC receptor 4 on the effects and mechanisms
      of pain. Taken together, chemokines and their receptors are potential targets for
      the development of novel pain management and therapy.

PMID- 30276313
TI  - Limiting exercise inhibits neuronal recovery from neurological disorders.
AB  - Patients who are bedridden often suffer from muscular atrophy due to reduced
      daily activities and can become depressed. However, patients who undergo physical
      therapy sometimes demonstrate positive benefits including a reduction of
      stressful and depressed behavior. Regenerative medicine has seen improvements in
      two stem cell-based therapies for central nervous system disorders. One therapy
      is through the transfer of exogenous stem cells. The other therapy is a more
      natural method and focuses on the increasing endogenous neurogenesis and
      restoring the neurological impairments. This study overviews how immobilization
      induced disuse atrophy affects neurogenesis in rats, specifically hypothesizing
      that immobilization diminishes circulating trophic factor levels, like vascular
      endothelial growth factors or brain-derived neurotrophic factor, which in turn
      limits neurogenesis. This hypothesis requires the classification of the stem cell
      microenvironment by probing growth factors in addition to other stress-related
      proteins that correlate with exercise-induced neurogenesis. There is research
      examining the effects of increased exercise on neurogenesis while limiting
      exercise, which better demonstrates the pathological states of immobile stroke
      patients, remains relatively unexplored. To examine the effects of immobilization
      on neurogenesis quantitative measurements of movements, 5-bromo-2deoxyuridine
      labeling of proliferative cells, biochemical assays of serum, cerebrospinal fluid
      and neurological levels of trophic factors, growth factors, and stress-related
      proteins will indicate levels of neurogenesis. In further research, studies are
      needed to show how in vivo stimulation, or lack thereof, affects stem cell
      microenvironments to advance treatment procedures for strengthening neurogenesis
      in bedridden patients. This paper is a review article. Referred literature in
      this paper has been listed in the references section. The datasets supporting the
      conclusions of this article are available online by searching various databases,
      including PubMed. Some original points in this article come from the laboratory
      practice in our research center and the authors' experiences.

PMID- 30276314
TI  - Exogenous stem cells pioneer a biobridge to the advantage of host brain cells
      following stroke: New insights for clinical applications.
AB  - Stroke continues to maintain its status as one of the top causes of mortality
      within the United States. Currently, the only Food and Drug Administration (FDA)
      approved drug in place for stroke patients, tissue plasminogen activator (tPA),
      has a rigid therapeutic window, closing at approximately 4.5 h after stroke
      onset. Due to this short time frame and other restrictions, such as any condition
      that increases a patient's risk for hemorrhaging, it has been predicted that <5%
      of ischemic stroke patients benefit from tPA. Given that rehabilitation therapy
      remains the only other option for stroke victims, there is a clear unmet clinical
      need for treatment available for the remaining 95%. While still considered an
      experimental treatment, the utilization of stem cell therapies for stroke holds
      consistent promise. Copious preclinical studies report the capacity for
      transplanted stem cells to rescue the brain parenchyma surrounding the stroke
      induced infarct core. At present, the exact mechanisms in which stem cells
      contribute a robust therapeutic benefit remains unclear. Following stem cell
      administration, researchers have observed cell replacement, an increase in growth
      factors, and a reduction in inflammation. With a deeper understanding of the
      precise mechanism of stem cells, these therapies can be optimized in the clinic
      to afford the greatest therapeutic benefit. Recent studies have depicted a unique
      method of endogenous stem cell activation as a result of stem cell therapy. In
      both traumatic brain injury and stroke models, transplanted mesenchymal stromal
      cells (MSCs) facilitated a pathway between the neurogenic niches of the brain and
      the damaged area through extracellular matrix remodeling. The biobridge pioneered
      by the MSCs was utilized by the endogenous stem cells, and these cells were able
      to travel to the damaged areas distal to the neurogenic niches, a feat
      unachievable without prior remodeling. These studies broaden our understanding of
      stem cell interactions within the injured brain and help to guide both
      researchers and clinicians in developing an effective stem cell treatment for
      stroke. This paper is a review article. Referred literature in this paper has
      been listed in the references section. The datasets supporting the conclusions of
      this article are available online by searching various databases, including
      PubMed. Some original points in this article come from the laboratory practice in
      our research center and the authors' experiences.

PMID- 30276309
TI  - Prospective clinical biomarkers of caspase-mediated apoptosis associated with
      neuronal and neurovascular damage following stroke and other severe brain
      injuries: Implications for chronic neurodegeneration.
AB  - Acute brain injuries, including ischemic and hemorrhagic stroke, as well as
      traumatic brain injury (TBI), are major worldwide health concerns with very
      limited options for effective diagnosis and treatment. Stroke and TBI pose an
      increased risk for the development of chronic neurodegenerative diseases, notably
      chronic traumatic encephalopathy, Alzheimer's disease, and Parkinson's disease.
      The existence of premorbid neurodegenerative diseases can exacerbate the severity
      and prognosis of acute brain injuries. Apoptosis involving caspase-3 is one of
      the most common mechanisms involved in the etiopathology of both acute and
      chronic neurological and neurodegenerative diseases, suggesting a relationship
      between these disorders. Over the past two decades, several clinical biomarkers
      of apoptosis have been identified in cerebrospinal fluid and peripheral blood
      following ischemic stroke, intracerebral and subarachnoid hemorrhage, and TBI.
      These biomarkers include selected caspases, notably caspase-3 and its specific
      cleavage products such as caspase-cleaved cytokeratin-18, caspase-cleaved tau,
      and a caspase-specific 120 kDa alphaII-spectrin breakdown product. The levels of
      these biomarkers might be a valuable tool for the identification of pathological
      pathways such as apoptosis and inflammation involved in injury progression,
      assessment of injury severity, and prediction of clinical outcomes. This review
      focuses on clinical studies involving biomarkers of caspase-3-mediated pathways,
      following stroke and TBI. The review further examines their prospective
      diagnostic utility, as well as clinical utility for improved personalized
      treatment of stroke and TBI patients and the development of prophylactic
      treatment chronic neurodegenerative disease.

PMID- 30276315
TI  - Neuroinflammation in traumatic brain injury: A chronic response to an acute
      injury.
AB  - Every year, approximately 1.4 million US citizens visit emergency rooms for
      traumatic brain injuries. Formerly known as an acute injury, chronic
      neurodegenerative symptoms such as compromised motor skills, decreased cognitive
      abilities, and emotional and behavioral changes have caused the scientific
      community to consider chronic aspects of the disorder. The injury causing impact
      prompts multiple cell death processes, starting with neuronal necrosis, and
      progressing to various secondary cell death mechanisms. Secondary cell death
      mechanisms, including excitotoxicity, oxidative stress, mitochondrial
      dysfunction, blood-brain barrier disruption, and inflammation accompany chronic
      traumatic brain injury (TBI) and often contribute to long-term disabilities. One
      hallmark of both acute and chronic TBI is neuroinflammation. In acute stages,
      neuroinflammation is beneficial and stimulates an anti-inflammatory response to
      the damage. Conversely, in chronic TBI, excessive inflammation stimulates the
      aforementioned secondary cell death. Converting inflammatory cells from pro
      inflammatory to anti-inflammatory may expand the therapeutic window for treating
      TBI, as inflammation plays a role in all stages of the injury. By expanding
      current research on the role of inflammation in TBI, treatment options and
      clinical outcomes for afflicted individuals may improve. This paper is a review
      article. Referred literature in this paper has been listed in the references
      section. The data sets supporting the conclusions of this article are available
      online by searching various databases, including PubMed. Some original points in
      this article come from the laboratory practice in our research center and the
      authors' experiences.

PMID- 30276317
TI  - Drug treatments that optimize endogenous neurogenesis as a therapeutic option for
      stroke.
AB  - Cell death and neurogenesis have been examined after stroke in the subventricular
      zone of the adult mammalian brain. New research focuses on the use of drugs to
      improve the viability of neural progenitor cells in rats after stroke. The aim of
      the drugs is to lengthen the timeframe for stroke therapy by targeting the
      endogenous repair mechanism that follows injury. In this paper, we look at the
      broad state of stroke therapy to assess the effectiveness of endogenous
      neurogenesis-enhancing drugs on stroke. This paper is a review article. Referred
      literature in this paper has been listed in the reference section. The data sets
      supporting the conclusions of this article are available online by searching
      various databases, including PubMed. Some original points in this article come
      from the laboratory practice in our research center and the authors' experiences.

PMID- 30276316
TI  - Granulocyte-colony stimulating factor and umbilical cord blood cell
      transplantation: Synergistic therapies for the treatment of traumatic brain
      injury.
AB  - Traumatic brain injury (TBI) is now characterized as a progressive, degenerative
      disease and continues to stand as a prevalent cause of death and disability. The
      pathophysiology of TBI is complex, with a variety of secondary cell death
      pathways occurring which may persist chronically following the initial cerebral
      insult. Current therapeutic options for TBI are minimal, with surgical
      intervention or rehabilitation therapy existing as the only viable treatments.
      Considering the success of stem-cell therapies in various other neurological
      diseases, their use has been proposed as a potential potent therapy for patients
      suffering TBI. Moreover, stem cells are highly amenable to adjunctive use with
      other therapies, providing an opportunity to overcome the inherent limitations of
      using a single therapeutic agent. Our research has verified this additive
      potential by demonstrating the efficacy of co-delivering human umbilical cord
      blood (hUCB) cells with granulocyte-colony stimulating factor (G-CSF) in a murine
      model of TBI, providing encouraging results which support the potential of this
      approach to treat patients suffering from TBI. These findings justify ongoing
      research toward uncovering the mechanisms which underlie the functional
      improvements exhibited by hUCB + G-CSF combination therapy, thereby facilitating
      its safe and effect transition into the clinic. This paper is a review article.
      Referred literature in this paper has been listed in the reference section. The
      datasets supporting the conclusions of this article are available online by
      searching various databases, including PubMed. Some original points in this
      article come from the laboratory practice in our research center and the authors'
      experiences.

PMID- 30276318
TI  - Translating regenerative medicine techniques for the treatment of epilepsy.
AB  - Epilepsy is considered a chronic neurological disorder and is accompanied by
      persistent and diverse disturbances in electrical brain activity. While
      antiepileptic pharmaceuticals are still the predominant treatment for epilepsy,
      the advent of numerous surgical interventions has further improved outcomes for
      patients. Despite these advancements, a subpopulation continues to experience
      intractable seizures which are resistant to current conventional and
      nonconventional therapeutic options. In this review, we begin with an
      introduction to the clinical presentation of epilepsy before discussing the
      clinically relevant laboratory models of epilepsy. Finally, we explore the
      implications of regenerative medicine - including cell therapy, neuroprotective
      agents, and electrical stimulation - for epilepsy, supplemented with our
      laboratory's data. This paper is a review article. Referred literature in this
      paper has been listed in the references section. The datasets supporting the
      conclusions of this article are available online by searching various databases,
      including PubMed. Some original points in this article come from the laboratory
      practice in our research center and the authors' experiences.

PMID- 30276319
TI  - Endogenous repair mechanisms enhanced in Parkinson's disease following stem cell
      therapy.
AB  - This mini-review highlights the innovative observation that transplanted human
      neural stem cells can bring about endogenous brain repair through the stimulation
      of multiple regenerative processes in the neurogenic area (i.e., subventricular
      zone [SVZ]) in an animal model of Parkinson's disease (PD). In addition, we
      convey that identifying anti-inflammatory cytokines, therapeutic proteomes, and
      neurotrophic factors within the SVZ may be essential to induce brain repair and
      behavioral recovery. This work opens up a new area of research for further
      understanding the pathology and treatment of PD. This paper is a review article.
      Referred literature in this paper has been listed in the references section. The
      datasets supporting the conclusions of this article are available online by
      searching various databases, including PubMed. Some original points in this
      article come from the laboratory practice in our research center and the authors'
      experiences.

PMID- 30276321
TI  - Amniotic fluid as a source of engraftable stem cells.
AB  - The ability of stem cells to differentiate into various lineages has made them
      powerful tools of regenerative medicine and applicable to multiple human
      diseases. Of particular interest, amniotic fluid-derived stem cells (AFSC) have
      been characterized to express both adult and embryonic cell markers, indicating
      them as cells within an intermediate stage between embryonic and adult phenotype.
      AFSC can differentiate into cells of all three germ layers, including hepatic,
      myogenic, osteogenic, and neurogenic cell types. Furthermore, AFSC have minimal
      replicative senescence, retaining the ability to divide effectively for over 250
      doublings. These facts indicate that amniotic fluid may exist as a promising
      donor source of stem cells for the treatment of multiple clinically relevant
      conditions. Of particular interest is the convenience of harvesting stem cells
      from the amniotic fluid stem for the treatment of newborns, as well as for
      banking or cryopreserving purposes to be used at a later date. Importantly, the
      promise of amniotic fluid as a source of stem cells merits ongoing research into
      their potential therapeutic applications. This paper is a review article.
      Referred literature in this paper has been listed in the references section. The
      datasets supporting the conclusions of this article are available online by
      searching various databases, including PubMed. Some original points in this
      article come from the laboratory practice in our research center and the authors'
      experiences.

PMID- 30276320
TI  - Amniotic fluid stem cell models: A tool for filling the gaps in knowledge for
      human genetic diseases.
AB  - Induced pluripotent stem (iPS) cells have attracted attention in recent years as
      a model of human genetic diseases. Starting from the diseased somatic cells
      isolated from an affected patient, iPS cells can be created and subsequently
      differentiated into various cell types that can be used to gain a better
      understanding of the disease at a cellular and molecular level. There are
      limitations of iPS cell generation, however, due to low efficiency, high costs,
      and lengthy protocols. The use of amniotic fluid stem cells (AFS) presents a
      worthy alternative as a stem cell source for modeling of human genetic diseases.
      Prenatal identification of chromosomal or Mendelian diseases may require the
      collection of amniotic fluid which is not only useful for the sake of diagnosis
      but also from this, AFS cells can be isolated and cultured. Since AFS cells show
      some characteristics of pluripotency, having the capacity to differentiate into
      various cell types derived from all three germ layers in vitro, they are a well
      suited model for investigations regarding alterations in the molecular biology of
      a cell due to a specific genetic disease. This readily accessible source of stem
      cells can replace the necessity for generating iPS cells. Here, we expand on the
      applicability and importance of AFS cells as a model for discovery in the field
      of human genetic disease research. This paper is a review article. Referred
      literature in this paper has been listed in the references section. The data sets
      supporting the conclusions of this article are available online by searching
      various databases, including PubMed. Some original points in this article come
      from the laboratory practice in our research center and the authors' experiences.

PMID- 30276322
TI  - Colony stimulating factor-1 receptor as a treatment for cognitive deficits
      postfractionated whole-brain irradiation.
AB  - Whole-brain irradiation (WBI) is commonly used to treat primary tumors of the
      central nervous systems tumors as well as brain metastases. While this technique
      has increased survival among brain tumor patients, the side effects of including
      a decline in cognitive abilities that are generally progressive. In an effort to
      combat WBI side effects, researchers explored the treatment of colony stimulating
      factor-1 receptor (CSF-1R) inhibitor. Data show that when a CSF-1R inhibitor is
      administered with fractionated WBI treatment, there is a decline in the number of
      resident and peripheral mononuclear phagocytes, a decrease in dendritic spine
      loss and a reduction in functional and memory deficits. CSFR-1R inhibitors have
      displayed promising results as an effective counter-treatment for WBI-induced
      deficits. Further research is required to optimize treatment strategies,
      establish a treatment timeline and gain a better understanding of the long-term
      side effects of targeting CSF-1R as a treatment strategy for WBI symptoms. This
      paper is a review article. Referred literature in this paper has been listed in
      the references section. The datasets supporting the conclusions of this article
      are available online by searching various databases, including PubMed. Some
      original points in this article come from the laboratory practice in our research
      center and the authors' experiences.

PMID- 30276323
TI  - Hyperpyrexia in life-threatening central nervous system infection - It is the
      timepoint of fever which matters: A plea to select the best timing and optimal
      methods of temperature management.

PMID- 30276325
TI  - A focus on CXCR4 in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is one of the most common and devastating aging-related
      neurodegenerative diseases. Besides the well-known role of chemokines and their
      receptors in the immune system, they are widely expressed in the nervous system,
      where they play roles in the regulation of cell migration and neurotransmission.
      The chemokine CXC motif receptor 4 (CXCR4) is evolutionarily highly conserved
      seven-transmembrane G-protein-coupled receptors (GPCRs). It has been demonstrated
      that CXCL12/CXCR4 signaling pathway involved in the pathologic process of AD. In
      this review, we demonstrated the GPCR family proteins and summarized the
      relationship between CXCR4 and GPCR, CXCR4 and AD. The review aimed to provide
      the novel insight of CXCR4 into the early prevention of mild cognitive impairment
      and in the diagnosis and treatment of AD.

PMID- 30276326
TI  - Enhanced oxidative stress response and neuroprotection of combined limb remote
      ischemic conditioning and atorvastatin after transient ischemic stroke in rats.
AB  - BACKGROUND: Limb remote ischemic conditioning (LRIC) and atorvastatin (AtS) both
      provide neuroprotection in stroke. We evaluated the enhanced neuroprotective
      effect of combining these two treatments in preventing ischemia/reperfusion (I/R)
      induced cerebral injury in a rat model and investigated the corresponding
      molecular mechanisms. MATERIALS AND METHODS: Transient cerebral ischemia was
      induced in Sprague-Dawley male rats by middle cerebral artery occlusion (MCAO)
      for 90 min followed by reperfusion (I/R). Rats were divided into 5 groups, sham,
      I/R, I/R + AtS, I/R + LRIC and I/R + AtS + LRIC. Pretreatment with LRIC and/or
      AtS for 14 days before MCAO surgery. Infarct volume, neurological score, Western
      blot, immuno-histochemical analyses were performed. RESULTS: The combination of
      LRIC plus AtS pretreatment decreased infarct volume and inhibited neuronal
      apoptosis. Combination treatment achieved stronger neuroprotection than
      monotherapy with LRIC or AtS. These therapies reduced reactive oxygen species
      production in the peri-ischemia region, associated with significantly increased
      expression and activation of superoxide dismutase 1, hemeoxygenase 1 and nuclear
      factor erythroid 2-related factor 2. CONCLUSIONS: Both LRIC and AtS + LRIC
      treatments conferred neuroprotection in ischemic stroke by reducing brain
      oxidative stress. AtS plus LRIC is an attractive translational research option
      due to its ease of use, tolerability, economical, and tremendous neuroprotective
      potential in stroke.

PMID- 30276327
TI  - Safety and efficacy of remote ischemic conditioning in pediatric moyamoya disease
      patients treated with revascularization therapy.
AB  - BACKGROUND: Revascularization surgery has been the standard treatment to prevent
      ischemic stroke in pediatric Moyamoya disease (MMD) patients with ischemic
      symptoms. However, perioperative complications, such as hyperperfusion syndrome,
      new infarct on imaging, or ischemic stroke, are inevitable. Remote ischemic
      conditioning (RIC) is a noninvasive and easy-to-use neuroprotective strategy, and
      it has potential effects on preventing hyperperfusion syndrome and ischemic
      infarction. AIMS: The aim of this study is to investigate the safety and efficacy
      of RIC in pediatric MMD patients undergoing revascularization surgery. METHOD: A
      total of 60 pediatric MMD patients with one or more ischemic symptoms will be
      recruited and allocated in 1:1 ratio to the RIC group and sham group,
      respectively. Both RIC and sham RIC will be performed twice daily for 7
      consecutive days before revascularization surgery with different cuff pressures
      during the ischemia period (50 mmHg over-systolic blood pressure and 30 mmHg).
      Single photon emission computed tomography will be performed within 7 days
      preoperatively and 3 months postoperatively, respectively, to evaluate the
      cerebral perfusion status. Other outcomes, including safety, plasma biomarker,
      functional outcome, and the incidence of infarction and its size, will also be
      evaluated. CONCLUSION: This study will provide insights into the preliminary
      proof of principle, safety, and efficacy of RIC in pediatric MMD patients
      undergoing revascularization surgery therapy, and this data will provide
      parameters for future larger scale clinical trials if efficacious.

PMID- 30276324
TI  - Therapeutic hypothermia and targeted temperature management for traumatic brain
      injury: Experimental and clinical experience.
AB  - Traumatic brain injury (TBI) is a worldwide medical problem, and currently, there
      are few therapeutic interventions that can protect the brain and improve
      functional outcomes in patients. Over the last several decades, experimental
      studies have investigated the pathophysiology of TBI and tested various
      pharmacological treatment interventions targeting specific mechanisms of
      secondary damage. Although many preclinical treatment studies have been
      encouraging, there remains a lack of successful translation to the clinic and no
      therapeutic treatments have shown benefit in phase 3 multicenter trials.
      Therapeutic hypothermia and targeted temperature management protocols over the
      last several decades have demonstrated successful reduction of secondary injury
      mechanisms and, in some selective cases, improved outcomes in specific TBI
      patient populations. However, the benefits of therapeutic hypothermia have not
      been demonstrated in multicenter randomized trials to significantly improve
      neurological outcomes. Although the exact reasons underlying the inability to
      translate therapeutic hypothermia into a larger clinical population are unknown,
      this failure may reflect the suboptimal use of this potentially powerful
      therapeutic in potentially treatable severe trauma patients. It is known that
      multiple factors including patient recruitment, clinical treatment variables, and
      cooling methodologies are all important in yielding beneficial effects. High
      quality multicenter randomized controlled trials that incorporate these factors
      are required to maximize the benefits of this experimental therapy. This article
      therefore summarizes several factors that are important in enhancing the
      beneficial effects of therapeutic hypothermia in TBI. The current failures of
      hypothermic TBI clinical trials in terms of clinical protocol design, patient
      section, and other considerations are discussed and future directions are
      emphasized.

PMID- 30276329
TI  - Cerebral venous sinus thrombosis: A diagnostic challenge in a rare presentation.
AB  - Cerebral venous sinus thrombosis (CVST) is an uncommon, life-threatening
      condition with a variable clinical presentation that makes it a challenge of
      diagnosis. A 39-year-old male patient presented to the hospital with complete
      loss of conscious and admitted to Medical Intensive Care Unit for investigation
      without any obvious history that was difficult for diagnosis. In this case, the
      patient presented with coma that is a rare presentation of CVST with no obvious
      clinical history and he was male patient that means he is free of all gender
      specific risk factors of CVST. The brain computed tomography (CT) scan showed
      hypodense lesion in the left upper parietal region with no hemorrhage. The lesion
      was low-signal intensity (SI) on T1WIs and high SI on T2WIs and restricted on
      diffusion-weighted images like arterial infarctions, but magnetic resonance
      angiography (MRA) was normal that excluded arterial infarction. Gadolinium
      enhanced MR venography (MRV) showed the filling defect of CVST. CVST can be
      present by a mysterious clinical presentation that makes it as a challenge of
      diagnosis even by medical imaging by CT and MR imaging (MRI). A combination of
      MRI and MRV is the best, noninvasive, and nonionizing imaging modality for the
      diagnosis of CVST.

PMID- 30276328
TI  - Mild therapeutic hypothermia protects against cerebral ischemia/reperfusion
      injury by inhibiting miR-15b expression in rats.
AB  - OBJECTIVE: Mild hypothermia has a protective effect on ischemic stroke, but the
      mechanisms remain elusive. Here, we investigated microRNA (miRNA) profiles and
      the specific role of miRNAs in ischemic stroke treated with mild hypothermia.
      MATERIALS AND METHODS: Male adult Sprague Dawley rats were subjected to focal
      transient cerebral ischemia. Mild hypothermia was induced by applying ice packs
      around the neck and head of the animals. miRNAs expression profiles were detected
      in ischemic stroke treated with mild therapeutic hypothermia through miRNA chips.
      Reverse transcription-polymerase chain reaction (RT-PCR) was used to verify the
      change of miRNA array. Western blot and adenosine triphosphate (ATP) assay kits
      were used to detect the changes of protein expression and ATP levels,
      respectively. miR-15b mimic and its control were injected into the right lateral
      ventricle 60 min before the induction of ischemia. RESULTS: The results showed
      that mild hypothermia affected miRNAs profiles expression. We verified the
      expression of miR-15b and miR-598-3p by miRNA RT-PCR. miR-15b mimic inhibited the
      expression of its target, ADP ribosylation factor-like 2 (Arl2) protein, and
      decreased ATP levels in PC12 cells. Compared with the control, miR-15b mimic
      increased the infarct volume and aggravated the neurological function under
      normothermia or hypothermia treatment. Furthermore, the expression of Arl2 was
      decreased in the miR-15b mimic group under normothermia or hypothermia treatment.
      CONCLUSIONS: Mild therapeutic hypothermia affected miRNA profiles and protected
      against cerebral ischemia/reperfusion by inhibiting miR-15b expression in rats.
      miR-15b may be a potential target for therapeutic intervention in stroke.

PMID- 30276331
TI  - Cerebrospinal fluid circulation: What do we know and how do we know it?
AB  - The central nervous system's (CNS) complicated design is a double-edged sword. On
      the one hand, the complexity is what gives rise to higher order thinking; but on
      the other hand, damage to the CNS evokes its unforgiving nature. The
      cerebrospinal fluid (CSF) circulation system is an intricate system embedded in
      and around the CNS that has been the topic of debate since it was first described
      in the 18th century. It is underscored by the choroid plexus's distinct vascular
      network which has conventionally been seen as the most prominent structure in CSF
      production through a variety of active transporters and channels. Despite the
      ubiquity of this circulation system in vertebrates, some aspects remain
      understudied. Recent advances in scientific methodology and experimentation have
      proven to be effective tools for elucidating the mechanisms of the CSF
      circulation system and the pathological conditions associated with its
      malfunction. In this review, we capitulate the classical understanding of CSF
      physiology as well as a new, emerging theory on CSF production.

PMID- 30276332
TI  - Mid A1 blister aneurysm presenting with subarachnoid hemorrhage: Case report and
      review.
AB  - Blister aneurysms are uncommon and difficult-to-treat lesions. They are a
      substantial cause of morbidity and mortality when encountered. Here, we report a
      blister aneurysm of the mid A1 segment of the anterior cerebral artery presenting
      with diffuse basal subarachnoid hemorrhage (SAH). The aneurysm was treated by
      surgical clipping of the parent vessel. Postoperatively, there was no filling of
      the parent vessel or aneurysm. A treatment algorithm including direct surgical
      repair and flow diversion for ruptured blister aneurysms is described. A high
      level of suspicion should be maintained in the setting of angiographic-negative
      SAH with an asymmetrically diffuse pattern.

PMID- 30276333
TI  - Neuroprotective effects of tenuigenin on neurobehavior, oxidative stress, and tau
      hyperphosphorylation induced by intracerebroventricular streptozotocin in rats.
AB  - BACKGROUND: Tenuigenin (TEN), a major active component of the Chinese herb
      Polygala tenuifolia root, has been used to improve memory and cognitive function
      in Traditional Chinese Medicine for centuries. PURPOSE: The present study was
      designed to explore the possible neuroprotective effect of TEN on the
      streptozotocin (STZ)-induced rat model of sporadic Alzheimer's disease (sAD).
      METHODS: STZ was injected twice intracerebroventrically (3 mg/kg, ICV) on
      alternate days (day 1 and day 3) in Rats. Daily treatment with TEN (2, 4, and 8
      mg/kg) starting from the first dose of STZ for 28 days. Memory-related behaviors
      were evaluated using the Morris water maze test. Hyperphosphorylation of tau
      proteins in hippocampus were measured by western blot assay. Superoxide dismutase
      activities, malondialdehyde, glutathione peroxidase and 4-hydroxy-2-nonenal
      adducts contents were also measured in the hippocampus. RESULTS: Treatment with
      TEN significantly improved STZ-induced cognitive damage, markedly reduced changes
      in malondialdehyde and 4-hydroxy-2-nonenal adducts, and significantly inhibited
      STZ-induced reduction in superoxide dismutase and glutathione peroxidase
      activities in the hippocampus. In addition, TEN decreased hyperphosphorylation of
      tau resulting from intracerebroventricular STZ (ICV-STZ) injection, and Nissl
      staining results showed that TEN has protective effects on hippocampal neurons.
      CONCLUSION: These results provide experimental evidence demonstrating preventive
      effect of TEN on cognitive dysfunction, oxidative stress, and
      hyperphosphorylation of tau in ICV-STZ rats. This study indicates that TEN may
      have beneficial effects in the treatment of neurodegenerative disorders such as
      AD.

PMID- 30276334
TI  - The association between the ring finger protein 213 gene R4810K variant and
      intracranial major artery stenosis/occlusion in the Han Chinese population and
      high-resolution magnetic resonance imaging findings.
AB  - BACKGROUND AND PURPOSE: The ring finger protein 213 (RNF213) gene R4810K variant,
      a susceptibility locus for moyamoya disease (MMD), has recently been identified
      to be associated with intracranial major artery stenosis/occlusion (ICASO)
      without satisfying the diagnostic criteria of MMD in the Japanese population.
      However, further studies are needed to determine whether this variant is
      associated with ICASO in other populations and whether R4810K variant-related
      ICASO could be categorized as MMD. The aim of this study is to elucidate whether
      the R4810K variant was associated with ICASO among the Han Chinese population and
      potential histopathology of R4810K variant-related ICASO. MATERIALS AND METHODS:
      We conducted a case-control study to evaluate association and performed high
      resolution (HR) magnetic resonance imaging (MRI) to investigate arterial wall
      feature of ICASO. The R4810K variant was genotyped in 114 ICASO patients and 268
      controls. Then, patients with R4810K variant-related ICASO were subjected to HR
      MRI examination and presumptively diagnosed based on the characteristics thus
      observed. STATISTICAL ANALYSIS: The relationship between R4810K variant and ICASO
      was evaluated by Fisher's exact test with odds ratios (OR) and 95% confidence
      interval (CI). RESULTS: The R4810K variant was associated with ICASO and
      increased the risk for ICASO (P < 0.01; OR: 20.2; 95% CI: 2.5-163.11).
      Presumptive MMD was diagnosed in all female patients with R4810K variant.
      However, presumptive intracranial atherosclerotic stenosis was diagnosed in one
      of three males harboring this variant. CONCLUSIONS: The R4810K variant is a
      genetic risk factor for ICASO among the Han Chinese population and that R4810K
      variant-related ICASO should be identified as MMD in female but not uncertain in
      male patients.

PMID- 30276335
TI  - Reperfusion injury in the age of revascularization.

PMID- 30276330
TI  - Hypothermia and brain inflammation after cardiac arrest.
AB  - The cessation (ischemia) and restoration (reperfusion) of cerebral blood flow
      after cardiac arrest (CA) induce inflammatory processes that can result in
      additional brain injury. Therapeutic hypothermia (TH) has been proven as a brain
      protective strategy after CA. In this article, the underlying pathophysiology of
      ischemia-reperfusion brain injury with emphasis on the role of inflammatory
      mechanisms is reviewed. Potential targets for immunomodulatory treatments and
      relevant effects of TH are also discussed. Further studies are needed to
      delineate the complex pathophysiology and interactions among different components
      of immune response after CA and identify appropriate targets for clinical
      investigations.

PMID- 30276337
TI  - Effects of ischemic preconditioning on mitochondrial and metabolic
      neruoprotection: 5' adenosine monophosphate-activated protein kinase and
      sirtuins.
AB  - Stroke and cardiac arrest result in cerebral ischemia, a highly prevalent medical
      issue around the world, which is characterized by a reduction or loss of blood
      flow to the brain. The loss of adequate nutrient supply in the brain during
      ischemia results in neuronal cell death contributing to cognitive and motor
      deficits that are usually permanent. Current effective therapies for cerebral
      ischemia are only applicable after the fact. Thus, the development of
      preventative therapies of ischemia is imperative. A field of research that
      continues to show promise in developing therapies for cerebral ischemia is
      ischemic preconditioning (IPC). IPC is described as exposure to sublethal
      ischemic events, which induce adaptive changes that provide tolerance to future
      ischemic events. Through either transient sub-lethal ischemic events, or the
      actions of a preconditioning molecular mimetic, IPC typically results in
      augmented gene expression and cellular metabolism. A pivotal target of such
      changes in gene expression and metabolism is the mitochondrion. Direct and
      indirect effects on mitochondria by IPC can result in the activation of 5'
      adenosine monophosphate-activated protein kinase (AMPK), a master regulator of
      cellular metabolism. Changes in the activity of the posttranslational modifiers,
      SIRT1 and SIRT5, also contribute to the overall adaptive processes in cellular
      metabolism and mitochondrial functioning. In this review, we present recently
      collected evidence to highlight the neuroprotective interactions of mitochondria
      with AMPK, SIRT1, and SIRT5 in IPC. To produce this review, we utilized PubMed
      and previous reviews to target and to consolidate the relevant studies and lines
      of evidence.

PMID- 30276338
TI  - Low-temperature plasma radiofrequency ablation in phantom limb pain: A case
      report.
AB  - Phantom limb pain (PLP) and phantom limb sensations are common complications
      postamputation. PLP is defined as persistent painful sensations perceived in the
      missing portion of the amputated limb. Low-temperature plasma radiofrequency
      ablation (coblation) technology is a relatively new technology that has shown
      promise in treating neuropathic pain. This report illustrates the use of
      coblation technology on cervical nerve roots for PLP. Coblation of the cervical
      nerve root was performed. Three 17G puncture trocars were placed near the C5-C6,
      C6-C7, and C7-T1 intervertebral foramen with computed tomography (CT) guidance.
      Then, a coblation needle attached to low-temperature plasma multifunctional
      operation system was placed near the C8 nerve root through the puncture trocars.
      To locate the target nerve, single stimulation (lasting for 5 s, at 1 intensity)
      in "cut" and "coagulation" model was given to serve as a sensory stimulation
      test. The stimulation induced radiating pain of the stimulated nerve away from
      the stimulation site to confirm our target nerve. The needle location was
      redirected based on the reproduction of the patient's symptoms with minimal
      intensity. A CT-guided cervical nerve root coblation was performed to obtain
      longer PLP relief. The patient reported pain relief in PLP after the operation.
      At 1-, 3-, and 6-month postoperative review, PLP relief was achieved. Overall
      activity was improved and there was necessarily need for pain medications.
      However, the doses of medicine significantly decreased. The analgesic effect was
      stable during the 6-month follow-up period. Our report demonstrates that
      coblation technology is successful treatment for PLP in this case. It will supply
      us a novel navigation in PLP treatments. Meanwhile, this finding still needs
      additional study for confirmation.

PMID- 30276336
TI  - Cerebrovascular dysfunction with stress and depression.
AB  - Maintenance of adequate tissue perfusion through a dense network of cerebral
      microvessels is critical for the perseveration of normal brain function.
      Regulation of the cerebral blood flow has to ensure adequate delivery of
      nutrients and oxygen with moment-to-moment adjustments to avoid both hypo- and
      hyper-perfusion of the brain tissue. Even mild impairments of cerebral blood flow
      regulation can have significant implications on brain function. Evidence suggests
      that chronic stress and depression elicits multifaceted functional impairments to
      the cerebral microcirculation, which plays a critical role in brain health and
      the pathogenesis of stress-related cognitive impairment and cerebrovascular
      events. Identifying the functional and structural changes to the brain that are
      induced by stress is crucial for achieving a realistic understanding of how
      related illnesses, which are highly disabling and with a large economic cost, can
      be managed or reversed. This overview discusses the stress-induced alterations in
      neurovascular coupling with specific attention to cerebrovascular regulation
      (endothelial dependent and independent vasomotor function, microvessel density).
      The pathophysiological consequences of cerebral microvascular dysfunction with
      stress and depression are explored.

PMID- 30276339
TI  - Multifocal cerebral infarction as the first manifestation of occult malignancy:
      Case series of trousseau's syndrome and literature review.
AB  - Ischemic stroke as an initial presentation of malignancy is extremely rare and
      the underlying etiology is often ignored. The aim of this study is to outline the
      clues to occult malignancy in patients presenting with cerebral infarction
      initially. The clinical characteristics of total 19 patients with Trousseau's
      Syndrome presenting with cerebral infarction initially were analyzed. Among those
      patients, no conventional vascular risk factors were detected in 68% (13/19) of
      patients, and infarction occurring in multiple vascular distributions was found
      in 84% (16/19). Blood test showed thrombophilia in 79% (15/19) of patients with
      significantly elevated D-dimer, disseminated intravascular coagulopathy (DIC) in
      59% (11/19), and elevated levels of tumor makers in 47% (9/19). The prognosis of
      the 19 patients was poor, with 68% (13/19) of patients undergoing a relapse of
      stroke in short interval, and 84% (16/19) being reportedly to die in 6 months. In
      patients, who developed unexplained recurrent brain infarction involving multiple
      arterial territory, with laboratory evidence suggesting hypercoagulability
      (higher level of D-dimer, or DIC), Trousseau's Syndrome should be considered, and
      investigation for an occult malignancy was required.

PMID- 30276340
TI  - The role of vascular endothelial growth factor in angiogenesis and brain
      circulation after stroke.

PMID- 30276341
TI  - Impact of expanding large vessel occlusion thrombectomy time-windows in inner
      city Detroit.

PMID- 30276342
TI  - Novel drug targeting and delivery techniques: Avenues for the advancement of
      neuropharmacology.

PMID- 30276343
TI  - Health economics and quality of life in a feasibility RCT of paediatric acute
      appendicitis: a protocol study.
AB  - Background: Acute appendicitis is one of the most common acute surgical
      emergencies in children and accounts for an annual cost of approximately L50
      million to the National Health Service. Investigating alternative treatment
      options offers the best prospect of enhancing the quality of care for patients
      and potential opportunities for cost savings through better allocative
      efficiency. A feasibility randomised controlled trial (RCT) comparing a non
      operative treatment pathway with appendicectomy for children with acute
      uncomplicated appendicitis is underway (CONTRACT feasibility RCT). Aims: The
      prime objective of this economic substudy conducted alongside the CONTRACT
      feasibility RCT is to better understand and assess: (1) cost data collection
      tools and cost drivers by identifying patients' pathways and (2) patient quality
      of life by assessing alternative paediatric health-related quality of life
      (HRQoL) instruments. Outcomes from this study will inform a future efficacy RCT
      assessing the effectiveness and cost-effectiveness of non-operative treatment
      pathway for the treatment of acute uncomplicated appendicitis in children.
      Methods: The economic substudy will use individual-level data and will be
      conducted from the health system perspective over the study's 6-month follow-up
      period. Microcosting will include health resource and service use, while
      potential benefits acquired will be measured using the HRQoL measures, Child
      Health Utility 9D (CHU-9D) and Euroqol-5 dimensions and 5 levels (EQ-5D-5L). We
      will assess the appropriateness of using the cost per quality-adjusted life year
      framework in the future RCT, as well as testing and identifying the most suitable
      HRQoL instrument. Conclusions: The outcomes of the investigational economic
      substudy will be used to inform the design of our future definitive RCT. However,
      the result from this economic study will also provide a detailed description and
      account of the issues inherent in paediatric Economic Evaluations Alongside
      Clinical Trials with an emphasis on costing methods of interventions taking place
      in secondary care settings. Trial registration number: ISRCTN1583043.

PMID- 30276345
TI  - Grace H. Elta, MD, 2018 Rudolf V. Schindler Award Winner.

PMID- 30276346
TI  - Polyglycolic acid sheet fibrin glue filling method for esophageal fistula.

PMID- 30276347
TI  - Gastric plications for weight loss: distal primary obesity surgery endoluminal
      through a belt-and-suspenders approach.

PMID- 30276344
TI  - Pathology of Calcineurin and Mammalian Target of Rapamycin Inhibitors in Kidney
      Transplantation.
AB  - The recent evolution in immunosuppression therapy has led to significant
      improvement in short-term kidney allograft outcomes; however, this progress did
      not translate into similar improvement in long-term graft survival. The latter,
      at least in part, is likely to be attributed to immunosuppressant side effects.
      In this review, we focus on the histologic manifestations of calcineurin
      inhibitor and mammalian target of rapamycin inhibitor toxicity. We discuss the
      pathologic features attributed to such toxicity and allude to the lack of highly
      specific pathognomonic lesions. Finally, we highlight the importance of
      clinicopathologic correlation to achieve a meaningful pathologic interpretation.

PMID- 30276348
TI  - Endoscopic removal of a giant double-headed fibrovascular esophageal polyp.

PMID- 30276349
TI  - Maintaining hemostasis during third-space endoscopy.

PMID- 30276350
TI  - Endoscopic management of gossypiboma.

PMID- 30276351
TI  - Endoscopic intra-abdominal rescue therapy of a dislodged EUS-guided
      hepaticogastrostomy stent.

PMID- 30276352
TI  - Endoscopic closure of gastrocolic fistula using clips and detachable ligatures.

PMID- 30276353
TI  - Endoscopic submucosal dissection of a large cecal polyp using a scissor-type
      knife: implications for training in ESD.

PMID- 30276354
TI  - Modified over-the-scope clip with telescope endoscopic full-thickness resection
      for colonic adenoma involving diverticulum.

PMID- 30276355
TI  - Application of linked color imaging for detecting a previously bleeding colonic
      diverticulum.

PMID- 30276356
TI  - Mitigating lumen-apposing metal stent dislodgment and allowing safe, single-stage
      EUS-directed transgastric ERCP.

PMID- 30276357
TI  - Monocytes and Macrophages in Heart Valves: Uninvited Guests or Critical
      Performers?
AB  - Monocytes and macrophages are critical components of the myeloid niche of the
      innate immune system. In addition to traditional roles as phagocytes, this
      subsection of innate immunity has been implicated in its ability to regulate
      tissue homeostasis and inflammation across diverse physiological systems. Recent
      emergence of discriminatory features within the monocyte/macrophage niche within
      the last 5 years has helped to clarify specific function(s) of the subpopulations
      of these cells. It is becoming increasingly aware that these cells are likely
      implicated in valve development and disease. This review seeks to use current
      literature and opinions to show the diverse roles and potential contributions of
      this niche throughout valvulogenic processes, adult homeostatic function, valve
      disease mechanisms, and tissue engineering approaches.

PMID- 30276358
TI  - Biomechanical forces in tissue engineered tumor models.
AB  - Solid tumors are complex three-dimensional (3D) networks of cancer and stromal
      cells within a dynamic extracellular matrix. Monolayer cultures fail to
      recapitulate the native microenvironment and therefore are poor candidates for
      pre-clinical drug studies and studying pathways in cancer. The tissue engineering
      toolkit allows us to make models that better recapitulate the 3D architecture
      present in tumors. Moreover, the role of the mechanical microenvironment,
      including matrix stiffness and shear stress from fluid flow, is known to
      contribute to cancer progression and drug resistance. We review recent
      developments in tissue engineered tumor models with a focus on the role of the
      biomechanical forces and propose future considerations to implement to improve
      physiological relevance of such models.

PMID- 30276359
TI  - Evaluation of Peak Reflux Velocities with Vector Flow Imaging and Spectral
      Doppler Ultrasound in Varicose Veins.
AB  - Purpose Spectral Doppler ultrasound (SDUS) is used for quantifying reflux in
      lower extremity varicose veins. The technique is angle-dependent opposed to the
      new angle-independent Vector Flow Imaging (VFI) method. The aim of this study was
      to compare peak reflux velocities obtained with VFI and SDUS in patients with
      chronic venous disease, i. e., pathological retrograde blood flow caused by
      incompetent venous valves. Materials and Methods 64 patients with chronic venous
      disease were scanned with VFI and SDUS in the great or the small saphenous vein,
      and reflux velocities were compared to three assessment tools for chronic venous
      disease. A flow rig was used to assess the accuracy and precision of the two
      methods. Results The mean peak reflux velocities differed significantly (VFI:
      47.4 cm/s vs. SDUS: 62.0 cm/s, p<0.001). No difference in absolute precision
      (p=0.18) nor relative precision (p=0.79) was found. No correlation to disease
      severity, according to assessment tools, was found for peak reflux velocities
      obtained with either method. In vitro, VFI was more accurate but equally precise
      when compared to SDUS. Conclusion Both VFI and SDUS detected the pathologic
      retrograde flow in varicose veins but measured different reflux velocities with
      equal precision. VFI may play a role in evaluating venous disease in the future.

PMID- 30276360
TI  - Recent advances in colorectal cancer screening.

PMID- 30276361
TI  - Systemic treatment for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers with high
      mortality worldwide. Treatment options for patients with advanced stage HCC
      remain a great challenge. However, novel agents especially small molecule
      tyrosine kinase inhibitor and innovative immunotherapy demonstrate new promising
      therapeutic options for these patients. This review article summarizes systemic
      treatment options evaluated in HCC focusing on the most recently published data
      and ongoing studies.

PMID- 30276362
TI  - Tumor-associated macrophages (TAMs) as biomarkers for gastric cancer: A review.
AB  - Gastric adenocarcinoma is one of the most common types of cancer worldwide, with
      an incidence of a million new cases annually. In addition to having a high
      mortality rate due to often delayed detection and its poor response to cancer
      therapy, it also spreads aggressively. Inflammation has been shown to play a role
      in carcinogenesis. Consequently, macrophages are important in phagocytosis,
      antigen presenting and producing cytokines and growth factors. As a response to
      microenvironmental signals, they may polarize into tumor resisting M1 or tumor
      promoting M2 macrophages. Recently, studies have indicated that M2-type
      macrophage resembling tumor-associated macrophages (TAMs) might be used as an
      independent prognostic factor for gastric cancer. This review will discuss the
      possible use of TAMs as prognostic tools for gastric cancer and whether they are
      suitable for use in clinical environment.

PMID- 30276363
TI  - Progress in targeted therapy for breast cancer.
AB  - Breast cancer is a multistep, multifactorial, and heterogeneous disease.
      Significant transformations have occurred in the systemic management of breast
      cancer in the past decade. Due to the further understanding of pathogenesis,
      scientists have found plenty of signaling pathways and correspondingly
      therapeutic targets in breast cancer, such as hormone receptor, human epidermal
      growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR),
      vascular endothelial growth factor (VEGF), phosphoinositide-3-kinase (PI3K), v
      akt murine thymoma viral oncogene homolog (AKT), mechanistic target of rapamycin
      (mTOR), cyclin-dependent kinase 4/6 (CDK4/6), poly (adenosine diphosphate-ribose)
      polymerase (PARP), and programmed death-1 (PD-1). Targeted therapy, which
      optimizes the accuracy of antitumor activity and minimizes toxicity to normal
      tissues, plays a crucial role in breast cancer treatment in the era of precision
      medicine. In this review, we aimed to summarize the latest developments in
      targeted therapy for breast cancer and discuss the existing problems.

PMID- 30276364
TI  - Fine particulate matter (PM2.5): The culprit for chronic lung diseases in China.
AB  - Air pollution is a world public health problem. Particulate matter (PM), a mix of
      solid and liquid particles in the air, becomes an increasing concern in the
      social and economic development of China. For decades, epidemiological studies
      have confirmed the association between fine particle pollutants and respiratory
      diseases. It has been reported in different populations that increased Fine
      particulate matter (PM2.5) concentrations cause elevated susceptibility to
      respiratory diseases, including acute respiratory distress, asthma, chronic
      obstructive pulmonary disease, and lung cancer. This review will discuss the
      pathophysiology of PM2.5 in respiratory diseases, which are helpful for the
      prevention of air pollution and treatment of respiratory tract inflammatory
      diseases.

PMID- 30276365
TI  - Antineutrophil cytoplasmic antibodies-associated glomerulonephritis: From bench
      to bedside.
AB  - Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a
      group of autoimmune disorders that predominantly affects small vessels. The onset
      of the disease is closely associated with ANCA. Renal involvement, also known as
      ANCA-associated glomerulonephritis (AGN), is one of the most common
      manifestations of AAV. In this mini-review, we described the clinical and
      pathological features of AGN. We then focused on recent studies on the mechanism
      of acute kidney lesions, including fibrinoid necrosis and crescent formation.
      Following the basic aspects of kidney injury in AGN, we demonstrated the clinical
      importance of kidney injury in determining the outcome of patients with AGN. The
      prognostic value of the 2010 Histopathological Classification of AGN and
      validating studies were summarized. Finally, treatment and novel therapeutic
      strategies were introduced addressing the importance of optimizing management of
      this patient population.

PMID- 30276368
TI  - Polyethyleneimine methylenecarboxylate: a macromolecular DTPA analogue to chelate
      plutonium(iv).
AB  - Up until now, molecular chelating agents, such as diethylenetriamine pentaacetic
      acid (DTPA), have been the standard method for actinide human decorporation.
      Mainly active in blood serum, their distribution within the body is thus limited.
      To treat a wider range of organs affected by plutonium contamination, a potential
      new class of macromolecular decorporation agents is being studied.
      Polyethyleneimine methylenecarboxylate (PEI-MC) is one such example. It is being
      considered here because of its capacity for targeting the liver and bones.

PMID- 30276367
TI  - Noncovalent spin-labeling of RNA: the aptamer approach.
AB  - In the first example of site-directed spin-labeling of unmodified RNA, a
      pyrrolidine-nitroxide derivative of tetramethylrosamine (TMR) was shown to bind
      with high affinity to the malachite green (MG) aptamer, as determined by
      continuous-wave (CW) electron paramagnetic resonance (EPR), pulsed electron
      electron double resonance (PELDOR) and fluorescence spectroscopies.

PMID- 30276366
TI  - Usefulness of upright T wave in lead aVR for predicting short-term prognosis of
      patients with ischemic stroke.
AB  - Background: Upright T wave in lead aVR (TaVR) has recently been reported to be
      associated with cardiovascular death and mortality in general population and in
      patients with prior cardiovascular disease (CVD). However, the evidence for the
      predictive ability of TaVR in patients with ischemic stroke (IS) is lacking.
      Methods: A total of 625 consecutive patients with IS (mean age: 66 +/- 12 years;
      379 male) were enrolled in this study between January 2013 and December 2014.
      Patients were divided into upright TaVR (>=0 mV; n = 201) and negative TaVR (<0
      mV; n = 424) groups. All patients were evaluated with respect to clinical
      features and in-hospital clinical results. Results: Overall, the prevalence of
      upright TaVR was 32.2% at baseline. Patients with an upright TaVR were older, had
      a higher percentage of CVD and hypertension, higher level of MB isoenzyme of
      creatine kinase (CKMB), faster heart rate, higher rate of QT prolongation > 450
      ms, higher rate of negative T in lead II, higher rate of negative T in lead V6,
      higher rate of ST depression, and longer QTc duration. During the mean follow-up
      period of 20.0 +/- 5.8 months, 29 (4.6%) patients experienced all-cause death and
      12 (1.9%) patients experienced cardiovascular death, the primary end point.
      Concomitantly, 94 (15%) patients experienced recurrence of IS, the secondary end
      point. After adjusting for clinical covariates, upright TaVR was independently
      associated with all-cause death [hazard ratio (HR): 2.88, 95% confidence
      intervals (CI): 1.07-7.73], cardiovascular death (HR: 3.04, 95% CI: 1.07-8.64),
      and IS recurrence (HR: 1.86, 95% CI: 1.08-3.20). Conclusions: Upright TaVR in
      patients with IS is associated with increased mortality and recurrence of IS.

PMID- 30276371
TI  - Synthesis of multisubstituted pyrroles by nickel-catalyzed arylative cyclizations
      of N-tosyl alkynamides.
AB  - The synthesis of multisubstituted pyrroles by the nickel-catalyzed reaction of N
      tosyl alkynamides with arylboronic acids is reported. These reactions are
      triggered by alkyne arylnickelation, followed by cyclization of the resulting
      alkenylnickel species onto the amide. The reversible E/Z isomerization of the
      alkenylnickel species is critical for cyclization. This method was applied to the
      synthesis of pyrroles that are precursors to BODIPY derivatives and a
      biologically active compound.

PMID- 30276370
TI  - Mn-Fe layered double hydroxide nanosheets: a new photothermal nanocarrier for O2
      evolving phototherapy.
AB  - Iron-manganese layered double hydroxide nanosheets were developed as an effective
      photothermal nanocarrier for loading a photosensitizer. The catalase-like
      activity enables the nanosheets to decompose H2O2 into O2, overcoming tumor
      hypoxia and enhancing O2-dependent photodynamic therapy (PDT). The combination of
      PDT and photothermal therapy (PTT) can almost completely eliminate tumor tissues.

PMID- 30276373
TI  - Synthesis of selenocysteine-containing cyclic peptides via tandem N-to-S acyl
      migration and intramolecular selenocysteine-mediated native chemical ligation.
AB  - Selenocysteine-containing cyclic 8-mer peptides, which were designed to mimic the
      plausible catalytic tetrad of glutathione peroxidase, were successfully
      synthesized in one pot via tandem N-to-S acyl migration of N-alkylcysteine (NAC)
      containing selenopeptides and intramolecular selenocysteine-mediated native
      chemical ligation (Sec-NCL) of the generated thioesters.

PMID- 30276374
TI  - A single-step, electrochemical synthesis of nitrogen doped blue luminescent
      phosphorene quantum dots.
AB  - Herein, we report a one-step strategy for the electrochemical synthesis of
      nitrogen doped blue luminescent phosphorene quantum dots (NPQDs) from black
      phosphorus at room temperature. Nitrogen percentage in NPQDs can be varied by the
      appropriate choice of solvent and supporting electrolyte. NPQDs [average size 6
      +/- 1.5 nm (N = 50)] obtained in this work exhibit ca. 88.7% quantum efficiency.

PMID- 30276376
TI  - Charge transfer dynamics at the boron subphthalocyanine chloride/C60 interface:
      non-adiabatic dynamics study with Libra-X.
AB  - We report a study on the non-adiabatic molecular dynamics (NA-MD) of the charge
      transfer (CT) process in the boron subphtalocyanine chloride (SubPc)/fullerene
      (C60) interface using our newly implemented Libra-X software package, which is
      based on an interface of the Libra NA-MD library and the GAMESS electronic
      structure software. In particular, we address the following aspects of the
      simulation protocol: (a) the choice of the potential used to treat interatomic
      interactions and its effect on the structures of the complex and CT rates; (b)
      the choice of the electronic structure methodology used; and (c) the choice of
      the trajectory surface hopping (TSH) methodology used. From our analysis of the
      electronic structure, we suggest that the distortion of the SubPc conical
      structure affects orbital localization and that the "breathing" motion of SubPc
      drives the CT process in SubPc/C60. This study illustrates that the choice of the
      TSH methodology and electronic decoherence are crucial for the CT simulation. We
      extend our analysis of CT in SubPc/(C60)n models by increasing the number of C60
      molecules up to n = 4. We find that the details of the interfacial SubPc/(C60)n
      geometry determine the CT rate. Finally, we find the computed CT timescale to be
      in the range of 2.2-5.0 ps, which is in agreement with the experimentally
      determined timescale in the order of magnitude of ~10 ps. The developed open
      source Libra-X package is freely available on the Internet at
      https://github.com/Quantum-Dynamics-Hub/Libra-X.

PMID- 30276377
TI  - Synthesis of novel heteroleptic delocalised cationic pyrazole gold complexes as
      potent HepG2 cytotoxic agents.
AB  - A new series of cationic gold(i) pyrazole complexes were prepared in excellent
      yields as their perchlorate salts. Results of cell viability assays show that
      these novel complexes have good cytotoxic properties against the human HepG2
      cancer cell line. These complexes showed promising anti-cancer activities and to
      our knowledge, pyrazoles have never been tested against this cell line. The
      regioselectivity of the complexation is also discussed in regards to the
      substitution pattern of the pyrazoles.

PMID- 30276379
TI  - Nanocrystals of CuMSnS4 (M = In or Ga) for solar energy conversion applications.
AB  - Quaternary MIMIIIMIVXVI4 (I-III-IV-VI4) chalcogenides obtained by cross
      substitution of binary and ternary compounds remain relatively unexplored. We
      have for the first-time synthesized wurtzite and defect chalcopyrite phases of
      CuMSnS4 (M = In or Ga) in the form of nanocrystals. Optical measurements show
      that the CuMSnS4 (M = In or Ga) nanocrystals exhibit strong visible light
      absorption with band gap values between 1.15 and 1.4 eV, suitable for solar
      energy conversion applications.

PMID- 30276380
TI  - In vivo measurement of the dynamics of norepinephrine in an olfactory bulb
      following ischemia-induced olfactory dysfunction and its responses to
      dexamethasone treatment.
AB  - Information on the dynamics of molecules following olfactory dysfunction remains
      essential for understanding the molecular events involved in the pathological
      process of olfactory dysfunction. This study for the first time demonstrates a
      method based on the combination of in vivo microdialysis with high performance
      liquid chromatography (HPLC) and electrochemical detection (ECD) for the
      measurement of the dynamics of norepinephrine (NE) in the olfactory bulbs of
      Sprague-Dawley rats following olfactory dysfunction induced by brain ischemia and
      its responses toward dexamethasone treatment. The method possesses a high spatial
      resolution and benefits from in vivo microdialysis and high selectivity and is
      thus capable of measuring NE in the olfactory bulb of rats. With this method, the
      basal level of NE in the olfactory bulb was evaluated to be ca. 235 +/- 25 nM (n
      = 6). This level was found to increase by 260 +/- 90% at a time point of 240 min
      after brain ischemia with bilateral ligation of both common carotid arteries. The
      increase was found to be suppressed upon the treatment of the animals with 0.2%
      dexamethasone in the olfactory bulb. These results suggest that NE is involved in
      the pathological process of ischemia-induced olfactory dysfunction and this
      information is useful to further understand the molecular events involved in
      olfactory dysfunction.

PMID- 30276381
TI  - 1,4-Conjugate addition/esterification of ortho-quinone methides in a
      multicomponent reaction.
AB  - A novel 1,4-conjugate addition/esterification of ortho-quinone methides in a
      multicomponent reaction has been developed. In this protocol, numerous carboxylic
      acids, ynamides and in situ generated ortho-quinone methides could assemble
      rapidly to constitute this process for the synthesis of functionalized 3,3
      diarylpropanamides with sufficient structural diversity. Furthermore, the
      products could be transformed to an array of compounds.

PMID- 30276382
TI  - Molecular iodine-mediated formal [2+1+1+1] cycloaddition access to pyrrolo[2,1
      a]isoquinolines with DMSO as the methylene source.
AB  - A molecular iodine-mediated formal [2+1+1+1] cycloaddition for the efficient
      synthesis of pyrrolo[2,1-a]isoquinolines from acetophenones, 1,2,3,4
      tetrahydroisoquinoline (THIQ) and DMSO has been developed. Mechanistic studies
      revealed that DMSO served as the methylene source, and this novel protocol
      involves intermolecular cycloaddition of two in situ generated intermediates that
      enable efficient formation of one C-N bond and three C-C bonds via multiple
      sequential C-H functionalizations.

PMID- 30276383
TI  - The activation of carbon dioxide by first row transition metals (Sc-Zn).
AB  - The activation of CO2 by chloride-tagged first-row transition metal anions [ClM]-
      (M = Sc-Zn), was examined by mass spectrometry, quantum chemical calculations,
      and statistical analysis. The direct formation of [ClM(CO2)]- complexes was
      demonstrated in the reaction between [ClM]- and neutral CO2. In addition, the
      reverse reaction was investigated by energy-variable collisionally induced
      dissociation (CID) of the corresponding [ClM(CO2)]- anions generated in-source.
      Five different mono- and bi-dentate binding motifs present in the ion/CO2
      complexes were identified by quantum chemical calculations and the relative
      stability of each of these isomers was established and analyzed for all first-row
      transition metals based on the experimental and theoretical ion/molecule binding
      energies. It was found that the early first row transition metals form strong
      covalent bonds with the neutral CO2 molecule, while the late ones and in
      particular copper and zinc are weakly bonded. Using simple valence bond Lewis
      diagrams, the different binding motifs and their relative stabilities across the
      first row were described using multi-configurational self consistent field
      (MSCSCF) wavefunctions in a quantitative manner based on the electronic structure
      of the individual metals. This analysis provides an explanation for the change of
      the most favorite bonding motif of the transition metals with CO2 along the 1st
      transition metal row. The nature of the activated CO2 complex and the
      relationship between its stability and other structural and spectral properties
      was also analyzed by Principal Component Analysis (PCA) and artificial neural
      networks.

PMID- 30276384
TI  - HfO2/HfS2 hybrid heterostructure fabricated via controllable chemical conversion
      of two-dimensional HfS2.
AB  - While preparing uniform dielectric layers on two-dimensional (2D) materials is a
      key device architecture requirement to achieve next-generation 2D devices,
      conventional deposition or transfer approaches have been so far limited by their
      high cost, fabrication complexity, and especially poor dielectric/2D material
      interface quality. Here, we demonstrate that HfO2, a high-K dielectric, can be
      prepared on the top surface of 2D HfS2 through plasma oxidation, which results in
      a heterostructure composed of a 2D van der Waals semiconductor and its insulating
      native oxide. A highly uniform dielectric layer with a controlled thickness can
      be prepared; the possibility of unlimited layer-by-layer oxidation further
      differentiates our work from previous attempts on other 2D semiconducting
      materials, which exhibit self-limited oxidation up to only a few layers. High
      resolution transmission electron microscopy was used to show that the converted
      HfO2/HfS2 hybrid structure is of high quality with an atomically abrupt, impurity
      and defect-free interface. Density functional theory calculations show that the
      unlimited layer-by-layer oxidation occurs because oxygen atoms can barrierlessly
      penetrate into the HfS2 surface and the extracted sulfur atoms are absorbed into
      the oxygen vacancy sites within HfO2 under O-rich conditions. A top-gated field
      effect transistor fabricated with the converted HfO2/HfS2 hybrid structure was
      found to exhibit a low interface trap density Dit of 6 * 1011 cm-2 eV-1 between
      the HfS2 channel and the converted HfO2 dielectric, and a high on/off current
      ratio above 107. Our approach provides a low cost, simple, and ultraclean
      manufacturing technique for integrating 2D material into device applications.

PMID- 30276385
TI  - Optimized synthesis and indium complex formation with the bifunctional chelator
      NODIA-Me.
AB  - The bifunctional chelator NODIA-Me holds promise for radiopharmaceutical
      development. NODIA-Me is based on the macrocycle TACN (1,4,7-triazacyclononane)
      and incorporates two additional methylimidazole arms for metal chelation and an
      acetic acid residue for bioconjugation. The original two step synthesis was less
      than optimal due to low yields and the requirement of semi-preparative RP-HPLC
      purifications. Here, the overall yield for the preparation of NODIA-Me was
      improved two- to five-fold via two synthetic routes using different
      protection/deprotection techniques. This way, it was possible (1) to prepare of
      NODIA-Me on multi-gram scale and (2) to avoid time-consuming HPLC purifications.
      Inspired by recent results with nat/68Ga3+, preliminary studies on the
      radiolabeling properties and complex formation of NODIA-Me with nat/111In3+ were
      performed. Quantitative radiochemical yields were achieved at ambient temperature
      providing molar activities of ~30 MBq nmol-1, which could be increased to ~240
      MBq nmol-1 at 95  degrees C. At r.t., pH 5.5 was optimal for 111In-labeling, but
      quantitative yields were also achieved in the pH range from 5.5 to 8.2, when the
      reaction temperature was increased. Stability tests of 111In complexes in vitro
      revealed high kinetic stabilities in serum and ligand challenge experiments,
      which is a consequence of the formation of rigid 1 : 1 indium chelates as shown
      by NMR studies in solution. In summary, the new synthetic routes afford the BFC
      NODIA-Me in high yields and on large scale. Further, 111In complexation
      experiments broaden the scope of our chelating system for radiopharmaceutical
      applications.

PMID- 30276386
TI  - Heterogeneous Co(OH)2 nanoplates/Co3O4 nanocubes enriched with oxygen vacancies
      enable efficient oxygen evolution reaction electrocatalysis.
AB  - Heterogeneous Co(OH)2 nanoplate/Co3O4 nanocube hybrids with rich oxygen vacancies
      have been constructed through a controllable approach. The high surface areas of
      such unique nanohybrids together with abundant oxygen vacancies provide more
      surface active sites, which can facilitate the charge transfer and boost the
      exchange of intermediates. Specifically, the resultant Co(OH)2 nanoplate/Co3O4
      nanocube hybrids display outstanding oxygen evolution reaction (OER) performances
      with a low overpotential of 281 mV at 10 mA cm-2 and excellent durability after
      continuous CV of 3000 cycles, shedding light for large-scale applications in
      practical water splitting.

PMID- 30276387
TI  - Rapid synthesis of 3-amino isocoumarin derivatives from ynamides.
AB  - A novel and efficient fast synthesis of 3-amino isocoumarins in good to excellent
      yields is reported. These interesting scaffolds can be obtained either in a
      single step from readily available ynamides or in a two-step sequence from the
      corresponding alkynyl bromide after C-N cross-coupling. This protocol, which only
      requires a Bronsted or Lewis acid as a promoter, offers an alternative approach
      toward synthesizing 3-substituted isocoumarins under smooth and fast conditions.

PMID- 30276389
TI  - N-Rich carbon-coated Co3S4 ultrafine nanocrystals derived from ZIF-67 as an
      advanced anode for sodium-ion batteries.
AB  - Transition metal sulfides (TMSs) have been extensively studied as electrode
      materials for sodium-ion batteries by virtue of their high theoretical capacity.
      However, the poor cyclability limits the practical application of TMSs in sodium
      ion batteries. In this study, N-rich carbon-coated Co3S4 ultrafine nanocrystal
      (Co3S4@NC) was prepared by utilizing ZIF-67 as a precursor through continuous
      carbonization and sulfuration processes, exhibiting ultrafine nanocrystals with a
      diameter of about 5 nm. When utilized as the anode for sodium ion batteries, the
      nanohybrid material exhibits remarkable cycling performance with a high specific
      capacity of 420.9 mA h g-1 at the current density of 100 mA g-1 after 100 cycles,
      indicating that the cycling performance is strengthened by the nitrogen-doped
      carbon coating. Impressively, the obtained material shows good rate performances
      with reversible specific capacities of 386.7, 284.0, and 151.2 mA h g-1 at 400,
      1000, and 1400 mA g-1, respectively, due to the high surface-capacitance
      contribution and porous structure inherited from the precursor, which finally
      results in the increase in infiltration of electrolyte and the accelerating
      diffusion rate of Na+. This study sheds light on the routes to improve the
      performance of TMSs@nitrogen-doped carbon nanohybrid materials for sodium ion
      batteries.

PMID- 30276390
TI  - Local trapping of energetic holes at gold nanoparticles on TiO2.
AB  - Oxidation sites for plasmon-induced charge separation at gold nanocubes and
      nanorods on TiO2 were visualized by PbO2 deposition, and the sites were localized
      at plasmonic resonance sites. This indicates that energetic holes generated at
      those sites dominate the reactions, which can be applied to photo-nanofabrication
      beyond the diffraction limit.

PMID- 30276392
TI  - Competition between two cysteines in covalent binding of biliverdin to
      phytochrome domains.
AB  - In this work, we disclose a mechanism of competing chemical reactions of protein
      assembly for a bacterial phytochrome using modern methods of molecular modeling.
      The recently designed variant of a near-infrared fluorescent protein miRFP670
      shows novel and unexpected features of covalent binding of the biliverdin
      chromophore to cysteine residues in the phytochrome domains GAF and PAS. Upon
      protein assembly, biliverdin reacts either with a cysteine from GAF, or with two
      cysteines, one from GAF and one from PAS. We characterize computationally a model
      structure of the noncovalently bound biliverdin molecule inside the protein cleft
      of miRFP670 and model reactions of the covalent binding. Both cysteines, Cys20
      (PAS) and Cys253 (GAF), are located close to the electrophile C32 atom of
      biliverdin and can act as nucleophiles. The nucleophilic attack of Cys253 from
      the GAF domain results in a single C-S bond formation with an activation energy
      of 16 kcal mol-1. Another pathway, leading to the biliverdin adduct with two C-S
      bonds, is characterized by lower energy barriers, less than 11 kcal mol-1.
      Competition between these reaction pathways explains the experimentally obtained
      mixture of both adducts. On the basis of our first simulations of covalent BV
      binding to the phytochrome domains, we propose an approach of a direct
      experimental validation of the reaction mechanisms using IR vibrational
      spectroscopy.

PMID- 30276391
TI  - Wulff in a cage gold nanoparticles as contrast agents for computed tomography and
      photoacoustic imaging.
AB  - Nanostructures have potential for use in biomedical applications such as sensing,
      imaging, therapeutics, and drug delivery. Among nanomaterials, gold
      nanostructures are of considerable interest for biomedical research, owing to
      their bio-inertness, controllable surface chemistry, X-ray opacity, and optical
      properties. Gold nanocages are particularly attractive for imaging and
      therapeutic applications, because they strongly absorb light in the near infra
      red region which has high light transmission in tissue. However, the X-ray
      attenuation of nanocages is relatively low due to their hollow structure. In this
      study, for the first time, we sought to combine the attractive optical properties
      of nanoshells with the high payloads of solid nanoparticles and investigated
      their biomedical applications. Here, we report the engineering of Wulff in a cage
      nanoparticles via converting gold Wulff-shaped seeds into gold-silver core-shell
      structures and then performing a galvanic replacement reaction. The structure of
      these nanoparticles was determined using transition electron microscopy. This
      morphological transformation of gold nanoparticles shaped as truncated
      octahedrons into a complex Wulff in a cage nanoparticles during the reaction
      resulted in extensive changes in their optical properties that made these unique
      structures a potential contrast agent for photoacoustic imaging. We found that
      the Wulff in a cage nanoparticles had no adverse effects on the viabilities of
      J774A.1, Renca, and HepG2 cells at any of the concentrations tested. In vitro and
      in vivo experiments showed robust signals in both photoacoustic imaging and
      computed tomography. To the best of our knowledge, this is the first report of
      Wulff in a cage nanoparticles serving as a platform for multiple imaging
      modalities. This unique multifunctional nanostructure, which integrates the
      competencies of both core and shell structures, allows their use as contrast
      agents for photoacoustic imaging, computed tomography and as a potential agent
      for photothermal therapy.

PMID- 30276393
TI  - An alternative route for the synthesis of hydroxylated pillar[5]arene-based
      amphiphiles.
AB  - Conformational mobilities of the units and host-guest complexation with n
      octyltrimethylammonium hexafluorophosphate of the synthesized perbenzylated
      pillar[5]arenes were studied. The formed complex was confirmed by proton nuclear
      magnetic resonance spectroscopy and mass spectral analysis. Hydroxylated
      pillar[5]arene-based amphiphiles were synthesized by a co-cyclization strategy
      followed by catalytic hydrogenation. This approach unlocks the synthesis and the
      design of a wide range of structural manipulations to these amphiphilic
      pillararenes.

PMID- 30276394
TI  - Development of a novel optogenetic indicator based on cellular deformations for
      mapping optogenetic activities.
AB  - Optogenetic techniques have changed the landscape of neuroscience by offering
      high temporal and spatial mapping of the activities of genetically defined
      population of cells with optical controlling tools. The mapping of optogenetic
      activities demands optogenetic indicators whose optical properties change in
      response to cellular activities, but the existing optogenetic indicators only
      specifically characterize limited optogenetic activities. Here, we propose a
      novel optogenetic indicator based on cellular deformation to characterize the
      activities of optogenetically engineered cells. The cellular activities triggered
      by light stimulation lead to changes in the cell membrane structure and result in
      cellular deformation, which is measured by atomic force microscopy. The
      deformation recordings of the cells expressing channelrhodopsin-2 (ChR2) and the
      corresponding control experiments together confirm that the deformation is
      generated generally when the cells are exposed to light, which is also validated
      indirectly via the change in the Young's modulus of the cells before and after
      absorption of photons. The activities of cells expressing different subtypes of
      opsins were also recorded using the optogenetic indicator of cellular
      deformation. This study provides a novel and general optogenetic indicator based
      on cellular deformation for monitoring the activities of optogenetically
      engineered cells. Moreover, this new optogenetic indicator offers ever-better
      tools for the applications of optogenetic activity mapping and neural and brain
      imaging.

PMID- 30276395
TI  - Metal ion coordination enhancing quantum efficiency of ligand phosphorescence in
      a double-stranded helical chain coordination polymer of Pb2+ with nicotinic acid.
AB  - A new 1D phosphorescence coordination polymer (CP) [Pb2O(C6H4NO2)2]n (1; C6H4NO2
      = nicotinate) was synthesized by a solvothermal reaction and PbO was used as a
      Pb(ii) source instead of traditional Pb(ii) salts. This remarkably thermal-stable
      CP crystallizes in the space group I41/a. In the crystal structure of 1, two
      different Pb(ii) ions show a five-coordinated and hemidirected coordination
      geometry, two nonequivalent nicotinate ligands link to Pb(ii) ions in MU2
      eta1:eta1 and MU4-eta2:eta2 modes, and the hemidirected coordination polyhedra of
      Pb(ii) form a helical lead-oxide chain via an edge-sharing fashion along the c
      axis. Under ambient conditions, 1 emits cyan ligand-based phosphorescence with an
      absolute quantum yield as high as 59.4% and a lifetime of 9.86 ms under UV-light
      irradiation. Under the same conditions, nicotinic acid emits simultaneously
      fluorescence and phosphorescence with a total absolute quantum yield of 4.8%. The
      great enhancement of phosphorescence quantum yield in 1, regarding nicotinic
      acid, is assigned to the heavy atom effect of Pb(ii) and negligible pipi
      interaction between pyridyl rings. Noticeably, the vibronic fine structure is
      observed in the emission spectrum of 1 at room temperature. Additionally, 1 shows
      thermochromic behavior, and such functionality probably has realistic application
      in the field of temperature detection.

PMID- 30276396
TI  - A loop chain and a three-dimensional network assembled from a multi-dentate
      nitronyl nitroxide radical and M(hfac)2 (M = CoII, CuII).
AB  - A multi-dentate nitronyl nitroxide radical Nit-Ph-3,5-bIm (Nit-Ph-3,5-bIm = 2
      [3,5-bis(1-imidazole)-phenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide)
      reacted with Co(hfac)2.2H2O or Cu(hfac)2 to yield two novel 3d-radical complexes
      {[Co(hfac)2]2(Nit-Ph-3,5-bIm)}n1 and {[Cu(hfac)2]7(Nit-Ph-3,5-bIm)3}n2 (hfac- =
      hexafluoroacetylacetonate). In both compounds, the Nit-Ph-3,5-bIm radical ligand
      behaves as a tetradentate ligand to link four M(hfac)2 units in a MU4
      eta1:eta1:eta1:eta1-coordination mode via its two NO groups and two N atoms of
      imidazole, generating a unique loop chain for 1 and a three-dimensional framework
      for 2. The magnetic studies revealed a strong antiferromagnetic Co-ON exchange
      interaction in 1 while a ferromagnetic Cu-ON interaction is observed in 2. The dc
      magnetic behaviors of two complexes are analyzed by means of appropriate magnetic
      models. Furthermore, ac magnetic susceptibilities of the Co complex reveal slow
      relaxation of magnetization.

PMID- 30276397
TI  - Layer-by-layer preparation of 3D covalent organic framework/silica composites for
      chromatographic separation of position isomers.
AB  - A layer-by-layer approach was developed to prepare 3D covalent organic framework
      COF-300/silica composites (COF-300@SiO2) with uniform morphology as the
      stationary phase for high performance liquid chromatography separation of
      position isomers with high efficiency, selectivity and precision.

PMID- 30276398
TI  - Self-supported nickel-cobalt nanowires as highly efficient and stable
      electrocatalysts for overall water splitting.
AB  - The development and design of highly active and stable electrocatalysts based on
      cheap and Earth-abundant materials is critically important to enable water
      splitting as a desirable renewable energy source. Herein, we fulfill the
      significant electrochemical water splitting enhancement in both electrocatalytic
      activity and durability by constructing self-supported nickel-cobalt nanowire
      catalysts with abundant oxygen vacancies. Specifically, the rich oxygen vacancies
      can largely promote the oxygen evolution reaction (OER) activity of optimal
      Ni1Co1O2 NWs with a relatively low overpotential of 248 mV to drive a current
      density of 10 mA cm-2. More significantly, after the phosphorization of Ni1Co1O2
      NWs, the resultant Ni1Co1P NWs can also display excellent electrocatalytic
      hydrogen evolution reaction (HER) performances with an overpotential of only 101
      mV to achieve a current density of 10 mA cm-2. Furthermore, benefiting from the
      unique 1D nanowire structure, the synergistic effect, and the optimal Gibbs free
      energy for hydrogen evolution evolved from the phosphorization, the Ni1Co1O2
      NWs//Ni1Co1P NWs couple is thus highly active and stable for overall water
      electrolysis with a low voltage of 1.58 V at 10 mA cm-2, showing extraordinary
      promise for practical overall water splitting electrolysis.

PMID- 30276399
TI  - Electrically pumped Fabry-Perot microlasers from single Ga-doped ZnO microbelt
      based heterostructure diodes.
AB  - Semiconducting micro/nanostructures possessing naturally optical waveguiding
      behaviors and Fabry-Perot (F-P) like resonances are emerging as versatile
      building blocks for the assembly of photonic and optoelectronic devices, such as
      photodetectors, light-emitting diodes, lasers and so on. Individual ZnO
      micro/nanowires with a rectangular cross-section, such as microwires and
      microbelts possessing naturally smooth facets along both sides for good optical
      feedback, can be employed as an underlying F-P mode microcavity whilst as the
      gain medium for light amplification. In this context, electrically pumped F-P
      mode microlasers comprising a single ZnO:Ga microbelt and p-GaN substrate have
      been realized. By treating as the precondition, electrically driven exciton
      polariton light-emitting behavior was achieved from the heterojunction diodes,
      which could be ascribed to strong exciton-photon coupling and waveguided nature
      of the synthesized microbelts. Once the applied bias exceeded the threshold
      value, an electrically pumped F-P mode lasing behavior could be observed, the
      lasing peaks centered at 410.5 nm and 450.5 nm respectively, accompanied with a
      dramatic narrowing of the spectral line-width to be around 1.0 nm emerging on the
      waveguided emission spectrum. Therefore, the realization of electrically pumped F
      P mode lasing using single microbelt based heterojunction diodes opens the door
      not only to the fabrication of coherent light sources and model systems for
      waveguided resonators, but also affords a competitive candidate to develop
      electrically pumped and ultralow threshold polariton lasers.

PMID- 30276400
TI  - Synthesis of heterobimetallic gold(i) ferrocenyl-substituted 1,2,3-triazol-5
      ylidene complexes as potential anticancer agents.
AB  - 1,2,3-Triazol-5-ylidene (trz) complexes of gold(i) containing a ferrocenyl
      substituent on the C4-position of the trz ring were synthesized to yield the
      neutral heterobimetallic gold(i) trz chlorido (2), gold(i) trz phenyl (3), and
      the cationic gold(i) trz triphenylphospine (5) complexes. In order to compare the
      effect of silver(i) as central metal vs. gold(i), [Ag(trz)2]+ (4) was also
      prepared, while variation of the C4-1,2,3-triazol-5-ylidene substituent from a
      ferrocenyl to a phenyl group was done to prepare the monometallic analogue of 5,
      namely the cationic Au(i) trz triphenylphosphine complex 6. The complexes were
      characterised with spectroscopic and electrochemical methods, and the single
      crystal X-ray structures of 2-6 were determined. NMR stability studies of 5 as a
      representative example of the series of complexes were performed to confirm the
      stability of the complexes in the solvent dimethylsulfoxide and in aqueous
      solution. The anti-cancer potential of 5 was evaluated against the lung cancer
      cell lines A549 and H1975, and the human embryonic kidney cell line (HEK-293) was
      used as a non-cancer model. IC50 values of 0.89, 0.23 and 5.43 MUM, respectively,
      were obtained for A549, H1975 and HEK-293, respectively, indicating the activity
      and selectivity of 5 for cancer cells. Fluorescence microscopy experiments as a
      preliminary mode-of-action study evidenced an apoptotic cell death mechanism
      rather than necrotic cell death.

PMID- 30276402
TI  - Chain-propagation, chain-transfer, and hydride-abstraction by cyclic carbocations
      on water surfaces.
AB  - Atmospheric particles contain a wide range of oligomers, but the formation
      mechanism and the origin of complexity are still unclear. Here, we report the
      direct detection of carbocationic oligomers generated from the exposure of a
      series of cyclic unsaturated hydrocarbon gases to acidic water microjets through
      interface-sensitive mass spectrometry. By changing gas concentrations, H2O (D2O)
      solvent, bulk pH and comparing results from experiments on acyclic, cyclic, and
      aromatic compounds, we elucidated three competing reaction mechanisms: chain
      propagation (CP), chain transfer (CT), and hydride abstraction (HA). We found
      that conjugative pi-electron delocalization in the carbocation is the most
      important factor for the interfacial oligomerization processes. Our results
      showed that electrophilic attack on C[double bond, length as m-dash]C double
      bonds (CP and CT) is limited, and that on C-H single bonds (HA) is enhanced for
      carbocations lacking conjugation, which is not the case in bulk organic
      solutions. Carbocationic oligomers generated by the encounter of gaseous
      unsaturated hydrocarbons and acidic water surfaces potentially contribute to the
      molecular complexity in atmospheric particles.

PMID- 30276401
TI  - Beta-galactosidase-responsive synthetic biomarker for targeted tumor detection.
AB  - Tumor biomarkers are highly desirable for the screening of patients with a risk
      of tumor development and progression. Here, we report a beta-galactosidase (beta
      gal)-responsive acetaminophen (beta-GR-APAP) as a synthetic plasma biomarker for
      targeted tumor detection. Tumor beta-gal labeling via the recognition of tumor
      related antigen enabled the detection of a tumor using beta-GR-APAP.

PMID- 30276403
TI  - Rate exchange rather than relaxation controls structural recovery.
AB  - We observe structural recovery after an electric field step by probing the
      dielectric loss profile near its maximum, which displays a field-induced shift
      towards lower frequencies. These dynamics display time aging-time superposition
      (TaTS) for the majority of relaxation modes, thus implying homogeneous recovery
      dynamics. Although assumed by generally accepted models, the same modes can not
      be responsible for structural relaxation and for structural recovery, as the
      former is heterogeneous and the latter is homogeneous regarding the nature of the
      dynamics. This conflict is resolved by proposing that structural recovery is
      governed by rate exchange, a process that refers to the homogeneous fluctuations
      of rate constants in equilibrium and restores ergodicity more slowly than the
      relaxation observed as a simple correlation decay. This recognition has wide
      ranging consequences on how aging and nonlinear dynamics such as scanning
      calorimetry should be modeled.

PMID- 30276409
TI  - Ultra-sensitive microfluidic wearable strain sensor for intraocular pressure
      monitoring.
AB  - Wearable technologies have potential to transform healthcare by providing
      continuous measurements of physiological parameters. Sensors that passively
      monitor physiological pressure without using electronic components are ideal for
      wearable contact lenses because they are easy to interface with the cornea and
      the external environment. Here, we report a passive integrated microfluidic
      sensor with a novel transduction mechanism that converts small strain changes
      into a large fluidic volume expansion, detectable by a smart-phone camera. The
      optimization of the sensor architecture and material properties results in a
      linear and stable sensor response. We have shown that the sensor has a detection
      limit of <0.06% for uniaxial and <0.004% for biaxial strain. We embedded our
      sensor in silicone contact lenses and measured the intraocular pressure induced
      strain in porcine eyes in the physiological range. The sensor's continuous
      operation capability for >19 hours and a lifetime reaching >7 months demonstrate
      its potential for long-term ophthalmic monitoring applications.

PMID- 30276410
TI  - Trap state passivation and photoactivation in wide band gap inorganic perovskite
      semiconductors.
AB  - CsPbCl3 is a promising material to construct future short wavelength
      optoelectronic devices based on inorganic perovskite semiconductors. In this
      study, CsPbCl3 microcrystals were synthesized by a solution phase process. It was
      found that the photoluminescence (PL) intensities of the CsPbCl3 microcrystals
      can increase by up to five times under persistent irradiation of UV light without
      peak shifting, accompanied with an increased absorption coefficient above the
      band gap and decreased PL lifetime. This PL enhancement is a reversible process
      with excitation light switching on and off. The photoactivation process of the
      CsPbCl3 microcrystals is attributed to the passivation of the trap states.

PMID- 30276411
TI  - Aminative Umpolung cyclization for synthesis of chiral exocyclic vicinal
      diamines.
AB  - Chiral exocylic vicinal diamines are biologically and chemically important
      compounds, but they are not easy to make. In this paper, an interesting aminative
      Umpolung cyclization process has been developed. Aromatic aldehydes 6 bearing an
      electrophilic chiral sulfinimine group underwent imine formation with 2,2
      diphenylglycine (2), decarboxylation, and subsequent Umpolung cyclization,
      producing various trans-diamines 10 in 84-96% yields with high trans/cis ratios
      under very mild conditions. This work not only provides an efficient, clean, and
      mild method for the synthesis of chiral exocyclic vicinal diamines in one step
      but also represents a new application of aminative Umpolung strategy on
      intramolecular reactions.

PMID- 30276412
TI  - Sublimable cationic Ir(iii) phosphor using chlorine as a counterion for high
      performance monochromatic and white OLEDs.
AB  - Different from the previous design strategy, herein, a cationic Ir(iii) complex
      ([(ptbi)2Ir(bisq)]Cl) with a small chlorine as the counterion was synthesized,
      which realized the formation of a solid film via a vacuum-deposition process. The
      white OLED, employing it as an orange-emitting layer, achieved excellent
      performances with a brightness of 50 122 cd m-2, a CE of 25.5 cd A-1, an EQE of
      13.1%, accompanied by a low CE efficiency roll-off of 4.7%. These are the best
      results among evaporated cationic Ir(iii)-based white OLEDs reported so far.

PMID- 30276413
TI  - Competition between hydrogen bonds and van der Waals forces in intermolecular
      structure formation of protonated branched-chain alcohol clusters.
AB  - To investigate the influence of bulky alkyl groups on hydrogen-bonded (H-bonded)
      network structures of alcohols, infrared (IR) spectra of protonated clusters of 2
      propanol (2-PrOH) and tert-butyl alcohol (t-BuOH) were observed in the OH and CH
      stretch regions. In addition, by varying the tag species, the temperature
      dependence profile of the isomer population of H+(t-BuOH)n was revealed. An
      extensive search for stable isomers was performed using dispersion-corrected
      density functional theory methods, and temperature-dependent IR spectral
      simulations were done on the basis of the harmonic superposition approximation.
      The computational results qualitatively agreed with the observed size and
      temperature dependence of the H-bonded network structures of these protonated
      bulky alcohol clusters. However, the difficulty in the quantitative evaluation of
      dispersion was also demonstrated. It was shown that H+(2-PrOH)n (n = 4-7) have
      essentially the same network structures as the protonated normal alcohol clusters
      studied so far. On the other hand, H+(t-BuOH)n (n = 4-8) showed a clear
      preference for the smaller-membered ring structures, that is very different from
      the preference of the protonated normal alcohol clusters. The origin of the
      different structure preferences was discussed in terms of the steric effect and
      dispersion.

PMID- 30276414
TI  - Dynamic calorimetry and XRD studies of the nematic and twist-bend nematic phase
      transitions in a series of dimers with increasing spacer length.
AB  - A modulated and conventional DSC study of the transitions between the twist-bend
      nematic (Ntb), regular nematic (N) and isotropic liquid (Iso) phases was
      performed on a series of difluoroterphenyl-based dimers with (CH2)n spacers; n =
      5, 7, 9, 11. The enthalpy of Ntb-N transition decreases steeply with increasing
      n, while that of the N-Iso transition increases with n; hence, the greatest
      effect of increasing n is a lowering N phase enthalpy. Based on past and present
      X-ray scattering experiments, we estimate the average molecular conformation in
      the Ntb phase and perform torsion energy calculations on the spacer. From this,
      the lowering enthalpy of the N phase is attributed to the decreasing torsional
      energy cost of bringing the two terphenyls from an inclined twisted conformation
      in the Ntb phase, to almost parallel in the N phase. With increasing n the C-C
      bonds of the spacers twist less away from their trans conformation, thereby
      reducing the overall torsion energy of the N phase. It is speculated that the
      nearly continuous nature of the Ntb-N transition in n = 11 dimer is associated
      with the divergence of the helical pitch toward infinity which is intercepted by
      a final jump at the very weak (0.01 J g-1) first-order transition. Small-angle X
      ray scattering results suggest similar local cybotactic layering in both nematic
      phases, with four sublayers, i.e. tails, mesogens, spacers, mesogens.

PMID- 30276415
TI  - Estimation of Overdiagnosis of Lung Cancer in Low-Dose Computed Tomography
      Screening: A Secondary Analysis of the Danish Lung Cancer Screening Trial.

PMID- 30276416
TI  - Potential Effects of Bariatric Surgery and Reduced Interleukin 32 Levels on Type
      2 Diabetes and Its Comorbidities-Reply.

PMID- 30276417
TI  - Association between increased mortality rate and antibiotic dose adjustment in
      intensive care unit patients with renal impairment.
AB  - PURPOSE: Adjusting the antibiotic dose based on an estimation of the glomerular
      filtration rate (eGFR) may result in subdosing, which may actually be
      significantly more problematic for intensive care unit (ICU) patients than not
      adjusting the dose. The aim of this study was to assess the outcomes of
      antibiotic dose adjustment in ICU patients with renal impairment. METHODS: A
      retrospective cohort study was conducted in adult patients admitted to an ICU of
      a Brazilian hospital from January 2014 to December 2015. The eGFR was determined
      using Cockcroft-Gault and Modified Diet in Renal Disease equations for each day
      of hospitalization. Treatment failure was defined based on the clinical,
      laboratory, and radiological criteria. RESULTS: A total of 126 patients were
      assessed to meet the inclusion criteria and subsequently enrolled in the study
      (19.9% of patients admitted to the ICU during the study period). Of the 168
      opportunities for dose adjustment, 99 (58.9%) adjustments were made. The mean
      eGFR in the group with dose adjustment was lower than that in the group without
      dose adjustment (38.5 vs. 40.7 mL/min/1.73 m2, respectively). The treatment
      failure rate among patients with dose adjustment and those treated with the usual
      dose was 59.3 and 38.9%, respectively (p = 0.023), and the mortality rates in the
      respective groups were 74.1 and 55.5% (p = 0.033). An association between dose
      adjustment and treatment failure/mortality rates was also observed in the
      multivariate analysis including the prognostic score. CONCLUSIONS: In ICU
      patients with renal impairment, adjustments in antibiotic dose based on eGFR,
      significantly increased the risk of treatment failure and death.

PMID- 30276418
TI  - Ultrasound-guided intermediate cervical plexus and additional peripheral facial
      nerve block for carotid endarterectomy : A prospective pilot study.
AB  - BACKGROUND AND OBJECTIVES: Ultrasound-guided intermediate cervical plexus block
      with perivascular local anesthetic infiltration is an established anesthetic
      procedure for carotid endarterectomy. In this prospective pilot study an
      additional subplatysmal block of the superficial ansa cervicalis is presented for
      the first time. The target structures are the anastomoses between the facial
      nerve (cervical and marginal mandibular branches) and cervical plexus. METHODS:
      An ultrasound-guided intermediate cervical plexus block (20 ml of ropivacaine
      0.75%) was performed (n = 28). Then, depending on the individual sonoanatomy, 5
      ml of prilocaine 1% was injected into the carotid sheath (group 1: no
      perivascular infiltration, n = 14, group 2: perivascular infiltration, n = 14).
      The third step was subplatysmal injection of 5 ml of prilocaine 1% between the
      medial edge of the sternocleidomastoid muscle and the submandibular gland (n =
      28). The investigated parameters included the need for supplementation and block
      related side effects. RESULTS: The requirement for supplemental local anesthetic
      infiltration in the skin incision area was minimal at mean (M) 1.1 ml (standard
      deviation (SD) +/-2.4 ml). Perivascular infiltration in group 2 significantly
      decreased the total amount of local anesthetic supplemented: group 1 M = 4.2 ml
      (SD = +/-3.1 ml), group 2 M = 1.7 ml (SD = +/-2.0 ml) (p = 0.018). The incidence
      of block-related side effects was not significantly different between the two
      groups. CONCLUSION: This study presents an ultrasound-guided subplatysmal block
      of the superficial ansa cervicalis for the first time, with the aim of optimizing
      anesthesia quality during surgical interventions in the carotid triangle.

PMID- 30276419
TI  - Evidence for Gut-Associated Serratia symbiotica in Wild Aphids and Ants Provides
      New Perspectives on the Evolution of Bacterial Mutualism in Insects.
AB  - Many insects engage in symbiotic associations with diverse assemblages of
      bacterial symbionts that can deeply impact on their ecology and evolution. The
      intraspecific variation of symbionts remains poorly assessed while phenotypic
      effects and transmission behaviors, which are key processes for the persistence
      and evolution of symbioses, may differ widely depending on the symbiont strains.
      Serratia symbiotica is one of the most frequent symbiont species in aphids and a
      valuable model to assess this intraspecific variation since it includes both
      facultative and obligate symbiotic strains. Despite evidence that some
      facultative S. symbiotica strains exhibit a free-living capacity, the presence of
      these strains in wild aphid populations, as well as in insects with which they
      maintain regular contact, has never been demonstrated. Here, we examined the
      prevalence, diversity, and tissue tropism of S. symbiotica in wild aphids and
      associated ants. We found a high occurrence of S. symbiotica infection in ant
      populations, especially when having tended infected aphid colonies. We also found
      that the S. symbiotica diversity includes strains found located within the gut of
      aphids and ants. In the latter, this tissue tropism was found restricted to the
      proventriculus. Altogether, these findings highlight the extraordinary diversity
      and versatility of an insect symbiont and suggest the existence of novel routes
      for symbiont acquisition in insects.

PMID- 30276420
TI  - Oral ethinylestradiol-levonorgestrel attenuates cardiac glycogen and triglyceride
      accumulation in high fructose female rats by suppressing pyruvate dehydrogenase
      kinase-4.
AB  - Fructose (FRU) intake has increased dramatically in recent decades with a
      corresponding increased incidence of insulin resistance (IR), particularly in
      young adults. The use of oral ethinylestradiol-levonorgestrel (EEL) formulation
      is also common among young women worldwide. The present study aimed at
      determining the effect of EEL on high fructose-induced cardiac triglyceride (TG)
      and glycogen accumulation. The study also investigated the possible involvement
      of pyruvate dehydrogenase kinase-4 (PDK-4) in EEL and/or high fructose metabolic
      effects on the heart. Ten-week-old female Wistar rats were allotted into four
      groups. The control, EEL, FRU, and EEL + FRU rats received distilled water
      (vehicle, p.o.), 1.0 MUg ethinylestradiol plus 5.0 MUg levonorgestrel (p.o.), 10%
      fructose (w/v), and 1.0 MUg ethinylestradiol plus 5.0 MUg levonorgestrel and 10%
      fructose, respectively, daily for 8 weeks. Data showed that EEL or high fructose
      caused IR' impaired glucose tolerance' hyperlipidemia' increased plasma lactate,
      lactate dehydrogenase, PDK-4, uric acid, xanthine oxidase (XO), adenosine
      deaminase (ADA), malondialdehyde (MDA), cardiac uric acid, TG, TG/HDL-
      cholesterol, glycogen synthesis, MDA, and visceral fat content and reduced
      glutathione. High fructose also resulted in impaired pancreatic beta-cell
      function, hyperglycemia, and increased cardiac PDK-4, lactate synthesis, and
      mass. Nonetheless, these alterations were ameliorated in EEL plus high fructose
      rats. This study demonstrates that high fructose-induced myocardial TG and
      glycogen accumulation is attributable to increased PDK-4. Besides, EEL could be a
      useful pharmacological utility for protection against cardiac dysmetabolism by
      inhibiting PDK-4.

PMID- 30276422
TI  - Fatty masses of the abdomen and pelvis and their complications.
AB  - There are numerous common and rare macroscopic fat-containing masses found in the
      abdomen and pelvis. These include benign masses, such as lipoleiomyoma, ovarian
      teratoma, mesenteric teratoma, and lipoma, as well as malignant masses, including
      liposarcoma and malignant transformation of benign entities. Any mass may become
      symptomatic due to the development of a complication which may range from ovarian
      torsion to intussusception to hemorrhage. Imaging plays a vital role in diagnosis
      and treatment planning when confronted with a symptomatic fat-containing mass.

PMID- 30276421
TI  - Effects of the second-generation "bath salt" cathinone alpha
      pyrrolidinopropiophenone (alpha-PPP) on behavior and monoamine neurochemistry in
      male mice.
AB  - RATIONALE: Synthetic cathinones ("bath salts") are beta-ketone analogs of
      amphetamines, yet few studies have examined their potential neurotoxic effects.
      OBJECTIVE: In the current study, we assessed the persistent behavioral and
      neurochemical effects of exposure to the second-generation synthetic cathinone
      alpha-pyrrolidinopropiophenone (alpha-PPP). METHODS: Male, Swiss-Webster mice
      were exposed to alpha-PPP (80 mg/kg) using a binge-like dosing regimen (QID,
      q2h). Behavior was assessed 4-5 days after the dosing regimen, and neurochemistry
      was assessed the following day. Behavior was studied using the elevated plus
      maze, Y-maze, and novel object recognition tests. Regional levels of dopamine,
      serotonin, norepinephrine, and the major dopamine metabolite 3,4
      dihydroxyphenylacetic acid (DOPAC) were determined in the prefrontal cortex and
      striatum using high-pressure liquid chromatography. Additional experiments
      assessed the time courses of the effects of alpha-PPP on locomotor activity and
      core temperature using telemetry. RESULTS: Exposure to alpha-PPP significantly
      impaired performance in the Y-maze, decreased overall exploratory activity in the
      novel object recognition test, and resulted in regionally specific depletions in
      monoamine neurochemistry. In contrast, it had no significant effect on elevated
      plus maze performance or object discrimination in the novel object recognition
      test. The locomotor-stimulant effects of alpha-PPP were comparable to cocaine (30
      mg/kg), and alpha-PPP (80 mg/kg) did not induce hyperthermia. CONCLUSIONS: alpha
      PPP exposure results in persistent changes in exploratory behavior, spatial
      working memory, and monoamine neurochemistry. This research highlights potential
      dangers of alpha-PPP, including potential neurotoxicity, and suggests that the
      mechanisms underlying the persistent untoward effects of the cathinones may be
      distinct from those of the amphetamines.

PMID- 30276423
TI  - Heavy metal accumulation in Lathyrus sativus growing in contaminated soils and
      identification of symbiotic resistant bacteria.
AB  - In this study, two populations of leguminous plants Lathyrus sativus were grown
      in four soils that were collected from sites differently contaminated by heavy
      metals. Evaluations included basic soil properties, concentrations of major
      nutrients and four metals (copper, zinc, lead and cadmium) in these soils.
      Investigation of Lathyrus sativus response to contamination showed that the
      increase of heavy metal concentration in soils affected biomass of plant, number
      of nodules and plant metal uptake. Heavy metal tolerance of 46 isolated bacteria
      from the root nodules was evaluated and demonstrated that the maximum
      concentration of Cd, Pb, Cu and Zn tolerated by strains were 0.8, 2.5, 0.2, and
      0.5 mM, respectively. Twenty-two isolates were tested for their effects on plant
      biomass production and nodule formation and showed that only R. leguminosarum
      nodulated Lathyrus sativus, while some bacteria improved the shoot and root dry
      biomass. Sequences of their 16S rDNA gene fragments were also obtained and
      evaluated for tentative identification of the isolates which revealed different
      bacterial genera represented by Rhizobium sp, Rhizobium leguminosarum,
      Sinorhizobium meliloti, Pseudomonas sp, Pseudomonas fluorescens, Luteibacter sp,
      Variovorax sp, Bacillus simplex and Bacillus megaterium. The existence of Pb- and
      Cd-resistant genes (PbrA and CadA) in these bacteria was determined by PCR, and
      it showed high homology with PbrA and CadA genes from other bacteria. The tested
      resistant population was able to accumulate high concentrations of Pb and Cd in
      all plant parts and, therefore, can be classified as a strong metal accumulator
      with suitable potential for phytoremediation of Pb and Cd polluted sites. Heavy
      metal resistant and efficient bacteria isolated from root nodules were chosen
      with Lathyrus sativus to form symbiotic associations for eventual bioremediation
      program, which could be tested to remove pollutants from contaminated sites.

PMID- 30276425
TI  - Glucocorticoid treatment in juvenile idiopathic arthritis.
AB  - Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease
      of joints in childhood. Glucocorticoids are being used in JIA treatment
      effectively for decades. Although systemic glucocorticoid use decreased with the
      introduction of biologic drugs, intraarticular glucocorticoid injections (IAGI)
      with nonsteroidal anti-inflammatory drugs and non-biologic disease modifying anti
      rheumatic drugs (DMARDs) still remain the primary treatment in JIA, especially in
      oligoarticular subcategory. Systemic glucocorticoids are used mainly for severe
      JIA-associated complications such as macrophage activation syndrome (MAS),
      myocarditis, pericarditis, pleuritis, peritonitis, and severe anemia; as bridging
      therapy while waiting for the full therapeutic effect of DMARDs; and in certain
      occasions for patients with severe refractory uveitis. Since glucocorticoid
      administration is associated with many adverse events, it is important to use
      glucocorticoids in an optimum way balancing the risks and benefits. The aim of
      this review is to summarize the current knowledge on glucocorticoid treatment in
      JIA. A comprehensive literature search was conducted utilizing the Cochrane
      Library and MEDLINE/PubMed databases. The main topics include mechanism of
      action, dose, duration, adverse events, vaccination during glucocorticoid
      treatment, the place of glucocorticoids in JIA treatment guidelines and consensus
      treatment plans, glucocorticoid use in JIA-associated uveitis, MAS, and IAGI.
      Data from the literature provide guidance on how to use glucocorticoids in JIA
      treatment especially for IAGI and systemic use in systemic JIA and MAS. However,
      there is lack of evidence and need for prospective randomized studies in most
      parts including the indications in different JIA subcategories, optimum
      dose/route of administration/duration of treatment, and tapering strategies.

PMID- 30276424
TI  - Dose-dependent bradycardia as a rare side effect of corticosteroids: a case
      report and review of the literature.
AB  - Corticosteroids rank at the first place among the most commonly used
      immunosuppressive agents in the rheumatology practice. Although their
      conventional adverse effects including hyperglycemia, hypertension,
      hyperlipidemia, and osteoporosis are well-recognized and managed, steroid-induced
      cardiac arrhythmias are known to a lesser extent. In this regard, steroid
      associated bradycardia is rarely expected and not very well known. Reported cases
      of steroid-associated bradycardias in the literature predominantly have emerged
      during the course of intravenous high-dose (pulse) methylprednisolone (MP)
      administrations. In this paper, we report a patient who developed sinus
      bradycardia following 52 mg of oral MP administration, improved once the drug was
      discontinued but repeated with the re-administration. Hence, the patient was
      shifted to prednisolone (PRED), and again suffered bradycardia which recovered
      upon dose reduction. Presenting this case along with other similar rare cases in
      the literature, our aim is to draw attention of fellow rheumatologists, who
      widely use steroids, to bradycardia-a rare and dose-dependent side effect of
      steroids.

PMID- 30276426
TI  - [What is certain in the treatment of rheumatoid arthritis?]
AB  - Rheumatoid arthritis (RA) is the most important chronic inflammatory joint
      disease with a prevalence of 1%. When untreated the disease leads to joint
      destruction and therefore to functional restrictions of the patients and also to
      increased rates of cardiovascular and malignant diseases. After the
      pathophysiology of rheumatoid arthritis was better understood, in the last 20
      years biologics could be developed, which are directed against targets involved
      in the inflammatory process in RA. Since then the remission rates of RA have
      substantially increased. In 2017 Janus kinase (JAK) inhibitors were additionally
      approved for the treatment of RA in Germany. They further broaden the therapeutic
      options and, in contrast to biologics, are administered orally. The response
      rates to therapy are better the earlier the disease is diagnosed and treated.
      Patients in whom RA is suspected due to a new onset of polyarthritis, should
      therefore be promptly referred to a rheumatologist.

PMID- 30276427
TI  - [Influence of primary lymph node status of colorectal cancer on the development
      of pulmonary metastases and thoracic lymph node metastases].
AB  - BACKGROUND: The lungs are the second most common organ site for metastases in
      patients with colorectal cancer (CRC). Lymph node metastasis of CRC represents a
      prognostic factor for survival. OBJECTIVE: The present study investigated the
      influence of CRC lymph node metastasis on lung metastasis, in particular thoracic
      lymph node metastasis. MATERIAL AND METHODS: A retrospective analysis of 88
      patients (n = 56 male) with curative resection of lung metastases of CRC was
      performed. Primary endpoint: influence of lymph node status of CRC on lung
      metastases. Secondary endpoints: disease-free survival and overall survival.
      Statistical evaluation was carried out with SPSS. RESULTS: In 48 patients a
      positive lymph node status of CRC and in 9 patients an N+ status of lung
      metastases were determined. The lymph node status of the CRC significantly
      affected the incidence of synchronous metastases (p = 0.03), disease-free
      interval until formation of metachronous lung metastases (p = 0.012) and the
      overall survival of patients with CRC (p = 0.048). The 5-year survival rate for
      CRC patients with lung metastases was 48.7% after pulmonary metastasectomy.
      Thoracic lymph node involvement also significantly affected survival (p = 0.001).
      CONCLUSION: Screening for pulmonary metastases should be included in the staging
      and follow-up of all patients with CRC, especially in patients with a positive
      lymph node status of the CRC.

PMID- 30276428
TI  - [New strategies and materials in endoscopic vacuum therapy in the lower
      gastrointestinal tract].
AB  - BACKGROUND: Endoscopic vacuum therapy is a widespread method in the postoperative
      treatment of lower and upper gastrointestinal (GI) tract leakage. OBJECTIVE:
      There is an absence of further technical development of the standardized material
      from 2007 for the lower GI tract. MATERIAL AND METHODS: New strategies and new
      materials for endoscopic vacuum therapy are presented. RESULTS: Alternative
      strategies in sponge placement, use of open-pore film drainage, use of a multiple
      sponge system, rinsing catheter, electronic pumps etc. enable the successful
      treatment of very complex pelvic defects. CONCLUSION: The wide variability of
      pelvic defects often necessitates a change in therapeutic strategies during the
      course of treatment for an optimized outcome.

PMID- 30276429
TI  - [Rabies and Bornavirus encephalitis : Fatal emerging viral encephalitis-a
      potential problem for organ recipients].
AB  - A severe, often fatal encephalitis needs to be extensively and carefully
      clarified, especially when it occurs in a patient weeks or months after an organ
      transplantation. If the donor was viremic at the time of the organ removal or
      living viruses were present in the organ tissue, many viruses can be transferred
      to the organ recipient. This has been repeatedly reported in recent years and
      decades. In this overview rabies is discussed as a particularly important form of
      viral encephalitis, which is transferred via organs and always has a fatal
      outcome, because patients carry a high risk of infection for all caregivers.
      Bornavirus has been known in veterinary medicine for many decades and in human
      medicine has been discussed as possibly being associated with psychiatric
      diseases. Very recently Bornavirus has been identified as the causative pathogen
      of fatal encephalitis in organ recipients. The aim of this article is to raise
      awareness for rabies and Bornavirus disease in intensive care medicine and
      neurology for organ donors and those taking care of organ recipients. Prevention
      by knowledge can be lifesaving.

PMID- 30276430
TI  - [Self-assessment of treatment urgency on presentation to a neurological emergency
      department : Results of a patient survey].
AB  - BACKGROUND: The proportion of patients with neurological disorders as well as the
      absolute number of patients in German emergency departments is rising. OBJECTIVE:
      This article presents the results of a survey among patients with self-referral
      to a dedicated neurological emergency department (ED). We sought to find out if
      the individual evaluation of urgency for treatment was comparable for patients
      and physicians. METHODS: During a prospective trial to validate a new and
      specific neurological triage system over a time period of three months (October
      2015 to January 2016), patients who presented themselves to the ED were handed a
      questionnaire and asked to provide information on the symptoms, including
      duration and the subjective urgency for evaluation by a physician (priority 1-4,
      1 = emergency, 4 = elective). The results were descriptively evaluated and the
      subjective assessment of urgency was compared to the physicians' evaluation.
      RESULTS: From a total of 836 questionnaires, handed out to each patient with self
      referral to the neurological ED, 528 (63%) were returned and analyzed. The most
      common symptoms were headaches, vertigo, paralysis and sensory deficits. In 24%
      of the patients the symptoms had lasted less than 24 h, while in 35% the symptoms
      had persisted for over 1 week. Over half of the patients (55%) indicated that the
      symptoms needed an emergency evaluation by a physician, while only 3% actually
      required immediate medical attention according to the retrospective assessment by
      physicians. This discrepancy was similar even after classification into symptoms
      and symptom duration. Only 2.6% of the patients stated that the reason for
      presenting to the ED was the inability to obtain an outpatient appointment.
      DISCUSSION: Patients regarded their symptoms as being a medical emergency much
      more often than physicians did. This was independent of the symptoms and their
      duration. An objective triage for patients in an ED is necessary.

PMID- 30276432
TI  - [Reduction techniques in intramedullary nailing osteosynthesis].
AB  - Intramedullary nailing was originally conceived for the stabilization of shaft
      fractures of long bones. Due to new nail designs and multiple interlocking
      possibilities, the spectrum of nailing has significantly increased. Nailing of
      fractures beyond the isthmus is technically challenging because fractures need to
      be reduced before the nailing procedure starts. Indirect techniques of reduction
      include the use of an extension table, a large distractor or an external fixator.
      Direct reduction with pointed reduction forceps, lag screws, a cerclage wire or a
      short plate can optimize indirect reduction. The choice of the correct entry
      portal is of utmost importance for an optimal operative result. The location of
      the entry portal is dependent on the local anatomy and the bend of the nail. The
      optimal entry portal at the proximal tibia is directly behind the patellar tendon
      and accessible with the knee in more than 90 degrees  of flexion, alternatively
      through a suprapatellar approach with a slightly flexed knee joint. Insertion of
      the nail through the suprapatellar approach is possible without stress on the
      reduced fracture fragments. Blocking screws create an artificial isthmus in the
      metaphyseal area and force the guide wire in the desired direction. Blocking
      screws help to avoid axial malalignment during nail insertion. Interlocking of
      the nail with screws coming from different directions prevents secondary
      dislocation.

PMID- 30276431
TI  - [School-based tobacco prevention: the "Be Smart - Don't Start" program].
AB  - The competition for smoke-free classes, the "Be Smart - Don't Start" program has
      been implemented in Germany since 1997. Using contract management techniques,
      school classes participating in the competition commit themselves to abstain from
      smoking for six months. Classes report on a regular basis whether they have
      stayed smoke-free or not. After the end of the competition period, successful
      classes participate in a prize draw. The competition aimes to influence social
      norms.Over the past 20 years, the competition has become a major school-based
      intervention to prevent smoking in Germany. Several studies addressed process and
      outcome evaluation, cost-benefit efficacy and iatrogenic effects. Following the
      evidence so far, the intervention is feasible for implementation in school
      routines, evokes positive feedback in teachers and students, and reveals a
      positive cost-benefit ratio. Findings from controlled studies imply that negative
      side-effects are unlikely to occur and that participation in the competition
      affects the progression of smoking positively at least in the short term.

PMID- 30276433
TI  - Functional impairment triggered by altertoxin II (ATXII) in intestinal cells in
      vitro: cross-talk between cytotoxicity and mechanotransduction.
AB  - Intestinal cells are able to continuously integrate response to multiple
      stimuli/stressors; these include the concomitant activation of "chemically
      driven" pathways, of paramount importance in the response to toxicants, as well
      as physical stimulation derived from motility. Altertoxin II (ATXII, 0.1, 1 and
      10 uM), a mycotoxin produced by the food contaminant fungus Alternaria alternata
      was studied in HT-29 intestinal adenocarcinoma cells and in non-transformed
      intestinal epithelial cells, HCEC. One-hour incubation with ATXII was sufficient
      to trigger irreversible cytotoxicity in both cell types, as well as to modify
      cellular responses to concomitant pro-oxidant challenge (H2O2, 100-500 uM, DCF-DA
      assay) suggesting that even relatively short-time exposure of the intestinal
      cells could be sufficient to alter their functionality. Combination of ATXII (1
      uM) with physical stimulation typical of the intestinal compartment (shear
      stress) revealed differential response of tumor-derived epithelial cells HT-29 in
      comparison to HCEC, in particular in the localization of the transcription factor
      Nrf2 (NF-E2-related factor 2). Moreover, ATXII reduced the migratory potential of
      HCEC as well as their membrane fluidity, but had no respective impact on HT-29
      cells. Taken together, ATXII appeared to alter predominantly membrane
      functionality in HCEC thus hampering crucial functions for cellular
      motility/turnover, as well as barrier function of healthy intestinal cells and
      had very limited activity on the tumor counterparts.

PMID- 30276434
TI  - Excellent 10-year patient-reported outcomes and survival in a single-radius,
      cruciate-retaining total knee arthroplasty.
AB  - PURPOSE: Over 2 million Triathlon single-radius total knee arthroplasties (TKAs)
      have been implanted worldwide. This study reports the 10-year survival and
      patient-reported outcome of the Triathlon TKA in a single independent centre.
      METHODS: From 2006 to 2007, 462 consecutive cruciate-retaining Triathlon TKAs
      were implanted in 426 patients (median age 69 (21-89), 289 (62.5%) female).
      Patellae were not routinely resurfaced. Patient-reported outcome measures (SF-12,
      Oxford Knee Scores (OKS), satisfaction) were assessed preoperatively and at 1, 5
      and 10 years when radiographs were reviewed. Forgotten Joint Scores (FJS) were
      collected at 10 years. Kaplan-Meier survival analysis was performed. RESULTS: At
      10-11.6 years, 123 patients (128 TKAs) had died and 8 TKAs were lost to follow
      up. There were four aseptic failures (two cases of tibial loosening, two cases of
      instability) and four septic failures requiring revision. Symptomatic aseptic
      radiographic loosening was present in three further cases at 11 years. Four (1%)
      patellae were secondarily resurfaced. OKS score improved by 17.7 +/- 9.7 points
      at 1 year (p < 0.001), and was maintained at 34.7 +/- 9.6 at 10 years with FJS
      48.5 +/- 31.4. Patient satisfaction was 88% at each timepoint. Ten-year survival
      was 97.9% (95% confidence interval 96.5-99.3) for revision for any reason, 98.9%
      (97.7-100) for mechanical failure, and 98.6% (97.4-99.8) for aseptic loosening
      (symptomatic radiographic or revised). CONCLUSION: The Triathlon TKA continues to
      show excellent longer-term results with high implant survivorship, low rates of
      aseptic failure, consistently maintained PROMs and excellent patient satisfaction
      rates of 88% at 10 years. LEVEL OF EVIDENCE: II, Prospective cohort study.

PMID- 30276435
TI  - Kinematic alignment in total knee arthroplasty better reproduces normal gait than
      mechanical alignment.
AB  - PURPOSE: Kinematic alignment technique for TKA aims to restore the individual
      knee anatomy and ligament tension, to restore native knee kinematics. The aim of
      this study was to compare parameters of kinematics during gait (knee flexion
      extension, adduction-abduction, internal-external tibial rotation and walking
      speed) of TKA patients operated by either kinematic alignment or mechanical
      alignment technique with a group of healthy controls. The hypothesis was that the
      kinematic parameters of kinematically aligned TKAs would more closely resemble
      that of healthy controls than mechanically aligned TKAs. METHODS: This was a
      retrospective case-control study. Eighteen kinematically aligned TKAs were
      matched by gender, age, operating surgeon and prosthesis to 18 mechanically
      aligned TKAs. Post-operative 3D knee kinematics analysis, performed with an
      optoelectronic knee assessment device (KneeKG(r)), was compared between
      mechanical alignment TKA patients, kinematic alignment TKA patients and healthy
      controls. Radiographic measures and clinical scores were also compared between
      the two TKA groups. RESULTS: The kinematic alignment group showed no significant
      knee kinematic differences compared to healthy knees in sagittal plane range of
      motion, maximum flexion, abduction-adduction curves or knee external tibial
      rotation. Conversely, the mechanical alignment group displayed several
      significant knee kinematic differences to the healthy group: less sagittal plane
      range of motion (49.1 degrees  vs. 54.0 degrees , p = 0.020), decreased maximum
      flexion (52.3 degrees  vs. 57.5 degrees , p = 0.002), increased adduction angle
      (2.0-7.5 degrees  vs. - 2.8-3.0 degrees , p < 0.05), and increased external
      tibial rotation (by a mean of 2.3 +/- 0.7 degrees , p < 0.001). The post
      operative KOOS score was significantly higher in the kinematic alignment group
      compared to the mechanical alignment group (74.2 vs. 60.7, p = 0.034).
      CONCLUSIONS: The knee kinematics of patients with kinematically aligned TKAs more
      closely resembled that of normal healthy controls than that of patients with
      mechanically aligned TKAs. This may be the result of a better restoration of the
      individual's knee anatomy and ligament tension. A return to normal gait
      parameters post-TKA will lead to improved clinical outcomes and greater patient
      satisfaction. LEVEL OF EVIDENCE: III.

PMID- 30276436
TI  - Chronic lateral ankle instability increases the likelihood for surgery in
      athletes with os trigonum syndrome.
AB  - PURPOSE: The etiology and incidence of os trigonum syndrome in professional
      athletes is highly variable. There is a paucity of data to ascertain why some
      athletes evolve towards surgery whilst others remain asymptomatic. We
      hypothesized that a lateral ligament ankle injury would increase the likelihood
      for surgery in those athletes with os trigonum syndrome. METHODS: Eighty
      professional athletes with clinical and radiological signs of os trigonum
      syndrome were identified to ascertain the incidence of injury to the lateral
      ligamentous ankle complex (acute and chronic) by magnetic resonance imaging
      (MRI). This cohort was subdivided into 2 groups; a surgical (n = 40) and a non
      surgical (n = 40) cohort. Surgical division was decided if (1) the clinical hyper
      plantar flexion test was positive, (2) a positive diagnostic ultrasound-guided
      injection and (3) no improvement was observed after 6 weeks of conservative
      rehabilitation. RESULTS: From the surgical cohort, 37 players (94.1%) had a
      chronic lateral ankle ligament injury on MRI, whilst 3 players (5.9%) had an
      acute lateral ankle ligament injury. Binary logistic linear modelling revealed
      that having a chronic lateral ligament injury increases the likelihood of os
      trigonum syndrome surgery by ten times compared to those with an acute lateral
      ligament injury. CONCLUSION: Professional athletes with chronic lateral ligament
      ankle injury have an approximate ten times greater risk for os trigonum syndrome
      surgery compared to athletes with acute lateral ligament ankle injury. LEVEL OF
      EVIDENCE: IV.

PMID- 30276437
TI  - High patient satisfaction with significant improvement in knee function and pain
      relief after mid-term follow-up in patients with isolated patellofemoral inlay
      arthroplasty.
AB  - PURPOSE: To prospectively evaluate the clinical and radiographic outcomes and
      survivorship at 2 and 5 years after isolated contemporary patellofemoral inlay
      arthroplasty. METHODS: Thirty-four patients were prospectively enrolled in the
      study and were evaluated preoperatively and at 2 and 5 years postoperatively.
      Clinical outcomes included the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) score and the visual analogue scale (VAS) for pain.
      Kellgren-Lawrence grading was used to assess the progression of tibiofemoral
      osteoarthritis and the Caton-Deschamps Index to determine patellar height. A
      Kaplan-Meier survival analysis was used to investigate the implant survivorship.
      Preoperative patient characteristics were compared among failures and success to
      determine potential risk factors and patient satisfaction was rated
      postoperatively. RESULTS: Five of the 34 patients were lost to follow-up
      resulting in a final follow-up rate of 86%. The total WOMAC subscores of pain and
      function and the VAS Pain improved significantly at 2- and 5-years, with no
      significant difference between the two time points. The WOMAC stiffness subscale
      reached significant improvement at 2-year follow-up alone. No significant
      progressions of tibiofemoral arthritis or changes in patellar height were
      observed. A total of six patients (17.1%) failed leaving a survival rate of 91%
      after 2 years and 83% after 5 years. The main cause for postoperative failure was
      persistent knee pain; however, no significant preoperative risk factor in patient
      characteristics could be identified. CONCLUSION: Patellofemoral inlay
      arthroplasty shows high patient satisfaction with significant improvement in knee
      function and pain relief after mid-term follow-up with no radiographic
      progression of tibiofemoral OA. LEVEL OF EVIDENCE: Prospective case series, Level
      III.

PMID- 30276438
TI  - Prognostic role of baseline 18F-FDG PET/CT metabolic parameters in Burkitt
      lymphoma.
AB  - PURPOSE: Burkitt's lymphoma (BL) is an aggressive lymphoma subtype with high 18F
      FDG avidity at 18F-FDG-PET/CT, but no validated criteria for PET/CT in treatment
      evaluation or prediction of outcome in BL are available. The aim of our study was
      to investigate whether the metabolic baseline PET/CT parameters can predict
      treatment response and prognosis in BL. MATERIALS AND METHODS: We retrospectively
      enrolled 65 patients who underwent baseline 18F-FDG-PET/CT, interim and end of
      treatment PET/CT. The PET images were analyzed visually and semi-quantitatively
      by measuring the maximum standardized uptake value body weight (SUVbw), the
      maximum standardized uptake value lean body mass (SUVlbm), the maximum
      standardized uptake value body surface area (SUVbsa), lesion to liver SUVmax
      ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), total
      metabolic tumor volume (tMTV) and total lesion glycolysis (TLG). Survival curves
      were plotted according to the Kaplan-Meier method. RESULTS: At a median follow-up
      of 40 months, the median PFS and OS were 34 and 39 months. MTV and TLG were
      significantly higher in patients with partial response compared to complete
      response group at end of treatment, while no significant differences were found
      at interim. Other metabolic PET/CT parameters were not related to treatment
      response. MTV and TLG were demonstrated to be independent prognostic factors for
      both PFS and OS; instead SUVbw, SUVlbm, SUVbsa, L-L SUV R and L-BP SUV R were not
      related to outcome survival. CONCLUSIONS: Metabolic tumour features (MTV and TLG)
      were significantly correlated with response to treatment and long-term outcome.

PMID- 30276439
TI  - NaF uptake in unstable plaque: what does fluoride uptake mean?

PMID- 30276440
TI  - Feasibility of multi-parametric PET and MRI for prediction of tumour recurrence
      in patients with glioblastoma.
AB  - BACKGROUND: Recurrence in glioblastoma patients often occur close to the original
      tumour and indicates that the current treatment is inadequate for local tumour
      control. In this study, we explored the feasibility of using multi-modality
      imaging at the time of radiotherapy planning. Specifically, we aimed to identify
      parameters from pre-treatment PET and MRI with potential to predict tumour
      recurrence. MATERIALS AND METHODS: Sixteen patients were prospectively recruited
      and treated according to established guidelines. Multi-parametric imaging with
      18F-FET PET/CT and 18F-FDG PET/MR including diffusion and dynamic contrast
      enhanced perfusion MRI were performed before radiotherapy. Correlations between
      imaging parameters were calculated. Imaging was related to the voxel-wise outcome
      at the time of tumour recurrence. Within the radiotherapy target, median
      differences of imaging parameters in recurring and non-recurring voxels were
      calculated for contrast-enhancing lesion (CEL), non-enhancing lesion (NEL), and
      normal appearing grey and white matter. Logistic regression models were created
      to predict the patient-specific probability of recurrence. The most important
      parameters were identified using standardized model coefficients. RESULTS:
      Significant median differences between recurring and non-recurring voxels were
      observed for FDG, FET, fractional anisotropy, mean diffusivity, mean transit
      time, extra-vascular, extra-cellular blood volume and permeability derived from
      scans prior to chemo-radiotherapy. Tissue-specific patterns of voxel-wise
      correlations were observed. The most pronounced correlations were observed for
      18F-FDG- and 18F-FET-uptake in CEL and NEL. Voxel-wise modelling of recurrence
      probability resulted in area under the receiver operating characteristic curve of
      0.77 from scans prior to therapy. Overall, FET proved to be the most important
      parameter for recurrence prediction. CONCLUSION: Multi-parametric imaging before
      radiotherapy is feasible and significant differences in imaging parameters
      between recurring and non-recurring voxels were observed. Combining parameters in
      a logistic regression model enabled patient-specific maps of recurrence
      probability, where 18F-FET proved to be most important. This strategy could
      enable risk-adapted radiotherapy planning.

PMID- 30276441
TI  - Guidelines for Perioperative Care in Esophagectomy: Enhanced Recovery After
      Surgery (ERAS(r)) Society Recommendations.
AB  - INTRODUCTION: Enhanced recovery after surgery (ERAS) programs provide a format
      for multidisciplinary care and has been shown to predictably improve short term
      outcomes associated with surgical procedures. Esophagectomy has historically been
      associated with significant levels of morbidity and mortality and as a result
      routine application and audit of ERAS guidelines specifically designed for
      esophageal resection has significant potential to improve outcomes associated
      with this complex procedure. METHODS: A team of international experts in the
      surgical management of esophageal cancer was assembled and the existing
      literature was identified and reviewed prior to the production of the guidelines.
      Well established procedure specific components of ERAS were reviewed and updated
      with changes relevant to esophagectomy. Procedure specific, operative and
      technical sections were produced utilizing the best current level of evidence.
      All sections were rated regarding the level of evidence and overall
      recommendation according to the evaluation (GRADE) system. RESULTS: Thirty-nine
      sections were ultimately produced and assessed for quality of evidence and
      recommendations. Some sections were completely new to ERAS programs due to the
      fact that esophagectomy is the first guideline with a thoracic component to the
      procedure. CONCLUSIONS: The current ERAS society guidelines should be reviewed
      and applied in all centers looking to improve outcomes and quality associated
      with esophageal resection.

PMID- 30276442
TI  - Removal of Acidity and Metals from Acid Mine Drainage-Impacted Water using
      Industrial Byproducts.
AB  - One of the biggest environmental impacts of mining is the generation of acid mine
      drainage (AMD). In the absence of proper post-mining management practices, AMD
      pollution can cause massive environmental damage. Current AMD management
      practices often fail to meet the expectations of cost, efficiency, and
      sustainability. The objective of this study was to utilize the metal-binding and
      acid-neutralizing capacity of an industrial by-product that is otherwise
      landfilled, namely drinking-water treatment residuals (WTRs), to treat AMD-water,
      thus offering a green remediation alternative. AMD-water was collected from Tab
      Simco coal mine in Carbondale, Illinois. It was highly acidic (pH 2.27), and
      contaminated with metals, metalloids and sulfate at very high concentrations. A
      filter media, prepared using locally-generated aluminum (Al) and calcium (Ca)
      based WTRs, was used to increase pH and to remove metals and [Formula: see text]
      from AMD-water. Laboratory-batch sorption studies at various WTRs (Al and Ca):AMD
      water ratios were performed to optimize the filter media. WTRs:sand ratio of 1:6
      provided optimal permeability, and 1:1 Al-WTRs:Ca-WTRs ratio was the optimal
      sorbent mix for removal of the metals of concern. A scaled-up study using a 55
      gallon WTRs and sand-based filter was designed and tested. The results showed
      that the filter media removed more than 99% of the initial Fe (137 mg/L), Al (80
      mg/L), Zn (11 mg/L), Pb (7 mg/L), As (4 mg/L), Mn (33 mg/L), and 44% of the
      initial [Formula: see text] (2481 mg/L) from Tab-Simco AMD-water. pH increased
      from 2.27 to 7.8. Desorption experiments showed that the metals were irreversibly
      bound to the WTRs and were not released back to the water.

PMID- 30276443
TI  - Serum miRNA-based distinct clusters define three groups of breast cancer patients
      with different clinicopathological and immune characteristics.
AB  - Breast cancer (BCa) is a heterogeneous disease with different histological,
      prognostic and clinical aspects. Therefore, the need for identification of novel
      biomarkers for diagnosis, prognosis and monitoring of disease, as well as
      treatment outcome prediction remains at the forefront of research. The search for
      circulating elements, obtainable by simple peripheral blood withdrawal, which may
      serve as possible biomarkers, constitutes still a challenge. In the present
      study, we have evaluated the expression of 6 circulating miRNAs, (miR-16, miR-21,
      miR-23alpha, miR-146alpha, miR-155 and miR-181alpha), in operable BCa patients,
      with non-metastatic, invasive ductal carcinoma, not receiving neoadjuvant
      chemotherapy. These miRNAs, known to be involved in both tumor cell progression
      and immune pathways regulation, were analyzed in relation to circulating
      cytokines, tumor immune-cell infiltration and established prognostic
      clinicopathological characteristics. We have identified three different clusters,
      with overall low (C1), moderate (C2) or high (C3) expression levels of these six
      circulating miRNAs, which define three distinct groups of non-metastatic BCa
      patients characterized by different clinicopathological and immune-related
      characteristics, with possibly different clinical outcomes. Our data provide the
      proof-of-principle to support the notion that, up- or down-regulation of the same
      circulating miRNA may reflect different prognosis in BCa. Nonetheless, the
      prognostic and/or predictive potential of these three "signatures" needs to be
      further evaluated in larger cohorts of BCa patients with an, at least, 5-year
      clinical follow-up.

PMID- 30276444
TI  - Female predisposition to TLR7-driven autoimmunity: gene dosage and the escape
      from X chromosome inactivation.
AB  - Women develop stronger immune responses than men, with positive effects on the
      resistance to viral or bacterial infections but magnifying also the
      susceptibility to autoimmune diseases like systemic lupus erythematosus (SLE). In
      SLE, the dosage of the endosomal Toll-like receptor 7 (TLR7) is crucial. Murine
      models have shown that TLR7 overexpression suffices to induce spontaneous lupus
      like disease. Conversely, suppressing TLR7 in lupus-prone mice abolishes SLE
      development. TLR7 is encoded by a gene on the X chromosome gene, denoted TLR7 in
      humans and Tlr7 in the mouse, and expressed in plasmacytoid dendritic cells
      (pDC), monocytes/macrophages, and B cells. The receptor recognizes single
      stranded RNA, and its engagement promotes B cell maturation and the production of
      pro-inflammatory cytokines and antibodies. In female mammals, each cell randomly
      inactivates one of its two X chromosomes to equalize gene dosage with XY males.
      However, 15 to 23% of X-linked human genes escape X chromosome inactivation so
      that both alleles can be expressed simultaneously. It has been hypothesized that
      biallelic expression of X-linked genes could occur in female immune cells, hence
      fostering harmful autoreactive and inflammatory responses. We review here the
      current knowledge of the role of TLR7 in SLE, and recent evidence demonstrating
      that TLR7 escapes from X chromosome inactivation in pDCs, monocytes, and B
      lymphocytes from women and Klinefelter syndrome men. Female B cells where TLR7 is
      thus biallelically expressed display higher TLR7-driven functional responses,
      connecting the presence of two X chromosomes with the enhanced immunity of women
      and their increased susceptibility to TLR7-dependent autoimmune syndromes.

PMID- 30276445
TI  - Sexual dimorphism in HIV-1 infection.
AB  - Sex-specific differences affecting various aspects of HIV-1 infection have been
      reported, including differences in susceptibility to infection, course of HIV-1
      disease, and establishment of viral reservoirs. Once infected, initial plasma
      levels of HIV-1 viremia in women are lower compared to men while the rates of
      progression to AIDS are similar. Factors contributing to these sex differences
      are poorly understood, and range from anatomical differences and differential
      expression of sex hormones to differences in immune responses, the microbiome and
      socio-economic discrepancies, all of which may impact HIV-1 acquisition and
      disease progression. Ongoing research efforts aiming at controlling HIV-1 disease
      or reducing viral reservoirs need to take these sex-based differences in HIV-1
      pathogenesis into account. In this review, we discuss established knowledge and
      recent findings on immune pathways leading to sex differences in HIV-1 disease
      manifestations, with focus on HIV-1 latency and the effect of female sex hormones
      on HIV-1.

PMID- 30276446
TI  - Sex-related factors in autoimmune liver diseases.
AB  - Autoimmune diseases are a broad range of diseases in which the immune system
      produces an inappropriate response to self-antigens. This results in
      inflammation, damage, or dysfunction of tissues and/or organs. Many autoimmune
      diseases are more common in women and differences between female and male immune
      and autoimmune responses have been well documented. In general, most of the
      autoimmune diseases seem to affect more females, although there are exceptions.
      Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary
      sclerosing cholangitis (PSC) are considered to be autoimmune liver diseases
      (AILD). They all are rare diseases and they result in significant morbidity and
      mortality. The female predominance in PBC and AIH are among the strongest among
      autoimmune diseases. However, the mechanisms responsible for the sex differences
      in autoimmune liver diseases are largely unknown. In this review, we discuss the
      recent findings on the influence of sex-dependent mechanisms, which may
      contribute to differences in presentation, clinical characteristics, disease
      course, and complications observed between female and male patients with
      autoimmune liver disease.

PMID- 30276447
TI  - The unhappy triad of the knee re-revisited.
AB  - AIM OF THE STUDY: To describe the surgical findings of the anterolateral complex
      in patients with the "unhappy triad" lesion of the knee. METHOD: One hundred and
      twenty-five consecutive patients presenting with acute anterior cruciate ligament
      (ACL) tears were selected for this study. Only cases, evaluated with a valgus
      stress test under fluoroscopy, with a medial opening more than 5 mm of the medial
      collateral ligament (MCL) were included in the study (11 patients). For the
      included cases, open MCL surgical repair was performed only in cases with a
      valgus stress test more than 10 mm as revealed by fluoroscopy (3 patients). All
      included cases (11 patients) underwent ACL reconstruction and exploration of the
      anterolateral complex that was then assessed, photographed, classified, and
      eventually repaired. RESULTS: At clinical evaluation under anaesthesia, all
      patients presented a positive Lachman test and a pivot shift test graded as ++ in
      four cases and +++ in five cases, not valuable in two cases. At surgical
      exploration, the anterolateral complex was involved in all cases (11 patients):
      one case demonstrated a type I injury, eight cases a type II injury, two cases a
      type III injury, and no patient with a type IV injury (Segond's fracture). All
      anterolateral complex lesions were repaired by direct suture and re-tensioning.
      DISCUSSION: On the basis of a recent analysis performed by other authors, we
      could speculate that injuries of ACL and anterolateral compartment occur in the
      very early phase of the injury when the knee is forced into internal rotation.
      The MRI evidence of bone bruising in the lateral compartment in most cases of the
      present series support the hypothesis of an internal rotation torque.
      CONCLUSIONS: The unhappy triad of injuries to the knee is actually a tetrad
      involving not just the ACL, MCL, and medial/lateral meniscus but also involved
      the anterolateral complex.

PMID- 30276448
TI  - Major emergency orthopaedic surgery in patients with a concomitant acute coronary
      event following trauma.
AB  - INTRODUCTION: This paper is a short series description of our experience with
      five cases managed surgically for orthopaedic trauma and who suffered meanwhile
      an acute coronary event. MATERIALS AND METHODS: Five polytrauma, multiply
      fractured patients were treated in our institution for various lesions, including
      an open femur and knee articular fractures, major fractures around the pelvis and
      hips. They had suffered around the same time an acute coronary event complicating
      the orthopaedic management. One patient was treated for the orthopaedic condition
      as a delayed emergency, with a five day retard due to pre-operative pulmonary
      oedema. Four patients had cardiac evaluation, angiogram or echocardiogram. The
      patients were managed by a multi-disciplinary team. RESULTS: One patient died
      post-operatively due to multiple complications, and four patients survived with a
      good functional outcome. CONCLUSIONS: Patients with acute orthopaedic polytrauma
      presenting concomitant acute coronary events should be treated by multi
      disciplinary teams, allowing early surgical management in a safe cardio-vascular
      and stable haemodynamic status.

PMID- 30276449
TI  - Long-term survivorship of a monoblock long cementless stem in revision total hip
      arthroplasty.
AB  - PURPOSE: The purpose of this study was to assess the clinical outcomes,
      complications, and survival of a long cementless titanium femoral stem in
      revision total hip arthroplasty (THA) at a minimum five year follow-up. METHODS:
      Between 2000 and 2010, 114 patients (116 hips), with a mean age of 68 +/- 12
      years, underwent revision THA using a KAR(r) stem (DePuy, Leeds, UK). The main
      reasons for revision were aseptic loosening (82%), periprosthetic joint
      infections (PJI) (11%), and periprosthetic fractures (6%). Mean follow-up was ten
      +/- three years (range, 5-16). Harris Hip Score (HHS), Oxford Hip Score (OHS),
      and Postel-Merle d'Aubigne (PMA) score were recorded. Radiographic analysis
      assessed stem osseointegration and subsidence. Survival was analyzed using the
      Kaplan-Meier (KM) method and cumulative incidence function (CIF). RESULTS: Post
      operative HHS was 83 +/- 15 (range, 35-99) and OHS was 37 +/- 8 (range, 8-48).
      PMA score significantly increased from 12 +/- 2 (range, 5-18) pre-operatively to
      14.6 +/- 2 (range, 9-18) post-operatively (p = 0.0004). The radiographic Engh
      score was 15 +/- 8 (range, 7-22). Stem subsidence was observed in two cases (3%).
      At ten years, five stems had been revised, three for infections and two for
      periprosthetic fractures. Using the KM method, ten year survival free of stem
      revision for aseptic loosening was 100%, free of revision for any reason 95%, and
      free of any re-operation 81%. CONCLUSIONS: The present study reported
      satisfactory outcomes and survival of a long tapered unlocked cementless femoral
      stem in revision THA at a minimum follow-up of five years.

PMID- 30276450
TI  - Patient satisfaction after total knee arthroplasty is better in patients with pre
      operative complete joint space collapse.
AB  - AIM OF THE STUDY: To determine if pre-operative radiologic minimal joint space
      width (mJSW) is related to the outcome of total knee arthroplasty (TKA) (primary
      hypothesis). Likewise, the aim was to test if pre-operative mJSW is related to
      prosthesis survival (secondary hypothesis). METHODS: A retrospective comparative
      analysis was performed. Group 1 was comprised of patients with pre-operative mJSW
      0-1 mm. Group 2 were patients with pre-operative mJSW >= 2 mm. The clinical
      outcome was determined with the Western Ontario and MacMaster Universities
      Osteoarthritis Index (WOMAC) score pre-operatively and one year after TKA. Only
      patients with pre-operative weight-bearing radiographs and complete WOMAC score
      data were accepted. RESULTS: Available for analysis were 377 patients, of whom
      188 were allocated to Group 1 (118 female, 70 male, age 70 +/- 11 years) and 189
      to Group 2 (118 female, 71 male, age 70 +/- 13 years). Pre-operative WOMAC total
      and WOMAC subscores showed no significant differences between groups. Post
      operatively, the WOMAC total was significantly better in Group 1 than in Group 2,
      10 +/- 22 and 19 +/- 31, respectively (p < 0.001, Power 97.5%). Similarly, the
      WOMAC subscores for pain, stiffness, and function were also significantly better
      in Group 1 than in Group 2. Five-year prosthesis survival was 94.2 and 91.6% in
      Groups 1 and 2, respectively (p = 0.07, Power 71%). DISCUSSION: Patients with pre
      operative complete joint space collapse (0 to 1 mm mJSW) achieve a significantly
      better WOMAC result from TKA than do those with a mJSW equal to or greater than 2
      mm. From our findings, it is recommended that "complete joint space collapse"
      especially be used as an indication for TKA surgery. CONCLUSION: Our study was
      underpowered to sufficiently show an effect of pre-operative mJSW on prosthesis
      survival.

PMID- 30276453
TI  - Lactobacillus supplementation prevents cisplatin-induced cardiotoxicity possibly
      by inflammation inhibition.
AB  - PURPOSE: Cardiotoxicity of chemotherapy exerts as the main hurdle for prognosis,
      while whether cisplatin causes severe cardiotoxicity remains largely unknown.
      Accumulating evidence reveals that intestinal microbiota functions importantly in
      nutrient metabolism and cardiovascular function. In this study, we observed the
      possible cardiotoxicity of cisplatin and explored the possible role of microbiota
      in the mouse model. METHODS: C57Bl6 mice were treated with 0, 3 or 6 mg/kg
      cisplatin via i.p. injection, together with or without Lactobacillus
      supplementation. Cardiac function was analyzed by echocardiography. Gut
      microbiota was analyzed by 16S RNA sequencing. Gene expression was analyzed by
      qPCR. The data differences were compared with Graphpad Prism 7.0. RESULTS: In
      comparison with the control group, 6 mg/kg per week cisplatin treatment for 3
      weeks significantly decreased the body weight by about 33% (18.1 +/- 2.1 vs 27.2
      +/- 0.9) and decreased the left ventricular ejection fraction by about 15% (0.57
      +/- 0.07 vs 0.67 +/- 0.04). Together, the gut microbiota was found dramatically
      changed, manifested as 27% decrease of Firmicutes and increased pathological
      bacteria. Antibiotics treatment had no obvious beneficial effects on the body
      weight and cardiac function caused by cisplatin. However, Lactobacillus
      supplementation significantly increased the body weight and restored cardiac
      function, together with lower inflammation gene expression. CONCLUSIONS: The
      study here has established a possible role of microbiota dysbiosis in cisplatin
      associated toxic effects, while delivery of Lactobacillus would be beneficial for
      the cardiac function prevention possibly via inflammation control.

PMID- 30276451
TI  - A phase II trial of EGFR-TKI readministration with afatinib in advanced non-small
      cell lung cancer harboring a sensitive non-T790M EGFR mutation: Okayama Lung
      Cancer Study Group trial 1403.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy of epidermal growth
      factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) readministration using
      afatinib in patients with non-small-cell lung cancer (NSCLC) with a sensitive non
      T790M EGFR mutation who had received cytotoxic chemotherapy after acquiring
      resistance to EGFR-TKIs. METHODS: Eligible patients had EGFR-mutant tumors
      resistant to first- or second-generation EGFR-TKIs and an EGFR-TKI-free period
      with cytotoxic agents. Confirmation of absence of the T790M mutation was required
      before registration. Afatinib (40 mg/body) was administered daily. The primary
      endpoint was progression-free survival (PFS). We assumed estimated and threshold
      PFS times of 3.3 and 1 months, with an alpha of 0.05 and beta of 0.1,
      respectively. RESULTS: Twelve patients were enrolled from December 2014 to May
      2017. The objective response rate and disease control rate were 17% and 84%,
      respectively. The median PFS time was 4.2 months (95% confidence interval [CI]
      2.0-5.8), which met the pre-defined primary endpoint. The median overall survival
      was 11.6 months (95% CI 9.2-not reached). Grade 3 or worse adverse events
      included diarrhea (25%), elevated creatinine levels (8%), and hypokalemia (8%),
      without any treatment-related deaths. CONCLUSION: EGFR-TKI readministration with
      afatinib for sensitive EGFR-mutant NSCLC without T790M after resistance to a
      first- or second-generation EGFR-TKI yielded modest activity with tolerable
      toxicity. It might be one of the treatment options in patients who do not possess
      T790M tumors, although further studies in this patient setting are warranted.

PMID- 30276455
TI  - Menstrual Cycle-Related Fluctuations in Breast Volume Measured Using Three
      Dimensional Imaging: Implications for Volumetric Evaluation in Breast
      Augmentation.
AB  - BACKGROUND: Breast volume is a key parameter of breast measurement in breast
      augmentation. However, the correlation between menstrual cycle phases and
      variation in breast volume has not been well studied. METHODS: Young female
      patients with regular menstrual cycles underwent eight three-dimensional imaging
      scans during a single menstrual cycle from November 2017 to January 2018. Breast
      volumetric difference at each timepoint and basic breast volume were measured for
      each subject. Preovulatory phase and postovulatory phase values were compared
      using an unpaired t test. A Pearson's linear correlated analysis was performed to
      identify the correlation between the basic breast volume and maximum range of
      breast volumetric difference during the menstrual cycle. RESULTS: Thirteen
      patients (26 breasts) met the inclusion criteria. During the menstrual cycle, the
      breast volumetric difference showed first a rising trend followed by a fall. A
      significant difference in the breast volumetric difference between the
      preovulatory phase and postovulatory phase (- 19.6 +/- 2.1 ml pre-ovulation vs. -
      6.9 +/- 3.3 ml post-ovulation, p = 0.002) was noted. There was a positive linear
      association between breast volume and maximum range of breast volumetric
      difference when a Pearson correlation was used (r = 0.45, p = 0.021).
      CONCLUSIONS: The breast volume fluctuates during the menstrual cycle, and there
      is a significant difference between the preovulatory phase and postovulatory
      phase for breast volumetric change. The influence of the menstrual cycle on
      breast volume should be taken into consideration by plastic surgeons performing
      breast augmentation. LEVEL OF EVIDENCE IV: This journal requires that authors
      assign a level of evidence to each article. For a full description of these
      Evidence-Based Medicine ratings, please refer to the Table of Contents or the
      online Instructions to Authors www.springer.com/00266 .

PMID- 30276454
TI  - Lowering of the High Eyelid Crease in Revision Upper Eyelid Surgery.
AB  - BACKGROUND: High placement of the lid crease is a common complication in upper
      eyelid surgery. Correction of the high crease by revision surgery is challenging
      and has not been well-reported. METHODS: This is a retrospective interventional
      study of patients who underwent revision eyelid surgery with lowering of the lid
      crease from 2008 to 2016 at a tertiary institution. Main outcome measures were
      pretarsal show (PTS) distance, lid crease symmetry, margin reflex distance 1
      (MRD1), and lid height symmetry. Lid crease symmetry was graded as symmetrical,
      mild asymmetry (PTS difference <= 0.5 mm), moderate asymmetry (PTS difference >
      0.5 mm but <= 1 mm), or obvious asymmetry (PTS difference > 1 mm). Lid height
      symmetry was graded as symmetrical, mild asymmetry (MRD1 difference <= 1 mm),
      moderate asymmetry (MRD1 difference > 1 mm but <= 2 mm), or obvious asymmetry
      (MRD1 difference > 2 mm). RESULTS: There were a total of 69 patients and 100
      eyes. The majority (n = 42, 60.9%) of patients were females. The mean age was
      38.3 +/- 17.3 years, and mean follow-up was 16 months. Mean PTS decreased from
      3.1 mm pre-surgery to 2.0 mm 2 years post-surgery. The proportion of patients
      with moderate or severe lid crease asymmetry decreased from 81.1% pre-surgery to
      6.7% 2 years post-surgery. The mean MRD1 difference decreased from 1.54 mm pre
      surgery to 0.23 mm 1 year post-surgery. The proportion of patients with moderate
      or severe lid height asymmetry improved from 64.5% preoperatively to 4.5% 1 year
      postoperatively. CONCLUSION: Revision eyelid surgery to correct a high crease is
      a challenging procedure. We present a technique that is effective in correcting
      the high lid crease, while simultaneously improving the lid height and lid crease
      symmetry. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level
      of evidence to each article. For a full description of these evidence-based
      medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 30276456
TI  - Bacterial Adhesion and Biofilm Formation on Textured Breast Implant Shell
      Materials.
AB  - BACKGROUND: Bacterial biofilms have been implicated with breast implant
      complications including capsular contracture and anaplastic large-cell lymphoma.
      The actual mechanisms for either are still under active investigation and are not
      clear. Due to their increased surface area, implants with textured surfaces may
      harbor greater biofilm loads than those with smooth surfaces. METHODS: Biofilm
      formation on the outer surface material was compared using implants with various
      surface areas and roughness, including Natrelle(r) (Smooth),
      SmoothSilk(r)/SilkSurface(r) (Silk), VelvetSurface (r) (Velvet), Siltex(r), and
      Biocell(r). The roughness and surface area of each material were assessed using
      non-contact profilometry. Bacterial attachment (2 h) and biofilm formation (24 h)
      were evaluated for Staphylococcus epidermidis, Pseudomonas aeruginosa, and
      Ralstonia pickettii over nine independent experiments using a CDC biofilm reactor
      and viable plate counts (VPCs) as well as confocal scanning laser microscopy.
      VPCs of the textured implants were compared relative to the Smooth implant.
      RESULTS: Surface areas increased with roughness and were similar among the three
      least rough implants (Smooth, Silk, and Velvet) and among the roughest implants
      (Siltex and Biocell). Overall, VPC indicated there was significantly more
      bacterial attachment and biofilm formation on the Siltex and Biocell implants
      than the Silk or Velvet implants, although there were differences between species
      and time points. CSLM confirmed the formation of thicker biofilms on the implants
      with rougher surface textures. CONCLUSION: This in vitro study confirmed that
      implant surfaces with rougher texture, resulting in more surface area, harbored
      greater biofilm loads than those with smoother surfaces. NO LEVEL ASSIGNED: This
      journal requires that authors assign a level of evidence to each submission to
      which Evidence-Based Medicine rankings are applicable. This excludes Review
      Articles, Book Reviews, and manuscripts that concern Basic Science, Animal
      Studies, Cadaver Studies, and Experimental Studies. For a full description of
      these Evidence-Based Medicine ratings, please refer to the Table of Contents or
      the online Instructions to Authors www.springer.com/00266 .

PMID- 30276452
TI  - Oncogenic roles of serine-threonine kinase receptor-associated protein (STRAP) in
      osteosarcoma.
AB  - PURPOSE: To validate the presence of serine-threonine kinase receptor-associated
      Protein (STRAP) in osteosarcoma tissue and to investigate the oncological role of
      STRAP in osteosarcoma. METHODS: Expression of STRAP protein in osteosarcoma
      tissue compared to soft callus (hyperactive bone healing tissue) and in multiple
      cell lines was examined using western blot analysis. Effects of STRAP silencing
      on cell proliferation, invasion, migration and re-implantability in chick
      chorioallantoic membrane (CAM) were observed in osteosarcoma cell lines (MNNG
      HOS, 143B, and U2OS). RESULTS: The result demonstrated that STRAP was highly up
      regulated in osteosarcoma tissues compared with the normal physiological bone
      healing tissue (soft callus). Expression level of STRAP was markedly high in
      osteosarcoma cell lines with aggressive phenotype. Upon STRAP silencing, invasion
      and migration, but not proliferative activity, were selectively modulated in high
      expression-STRAP cell lines. In addition, STRAP silencing reduced the success
      rate of tumor implantation and growth of MNNG-HOS cells in CAM model.
      CONCLUSIONS: Serine-threonine kinase receptor-associated protein is up-regulated
      during osteosarcoma progression. The presence of STRAP enhances osteosarcoma cell
      invasion, migration and re-implantation ability, factors which play a critical
      role in metastasis. Serine-threonine kinase receptor-associated protein and its
      related pathway are worthy for further exploration as a novel target for anti
      metastasis agents.

PMID- 30276457
TI  - Secondary Breast Augmentation: Is There a Trend for Bigger Implants?
AB  - BACKGROUND: Despite novel assessment tools and 3D simulation, patient's desire
      for implant size change is one of the most common reasons for revision surgery
      after primary breast augmentation. In this study, we analysed outcomes and
      predictive indicators for revision surgeries in a cohort of patients operated on
      by a single surgeon. PATIENTS AND METHODS: All consecutive patients who underwent
      revision augmentation surgery between 2013 and 2017 by the first author were
      included in this study. Besides review of medical records, subgroups based on the
      indication for revision surgery were compared and statistically analysed.
      RESULTS: A total of 110 patients were included in this study. Revision surgery
      was performed 97.2 months on average after primary augmentation. Eighty-six per
      cent of patients received larger implants. Indications for revision surgery and
      associated subgroups were: (1) wish for bigger implants (38%), (2) complication +
      wish for bigger implants (26%), (3) complication (29%), (4) complication + wish
      for smaller implants (3%) and (5) wish for smaller implants (3%). Subgroup
      analysis showed that patients who underwent revision surgery for bigger implants
      were significantly younger compared to patients who suffered a complication or
      desired smaller implants. Time to secondary augmentation was significantly
      shorter in case of wish for size change compared to complications as reason for
      revision surgery. Implant sizes differed significantly in patients where volume
      change was the sole indication for surgery compared to revisions performed due to
      complications. CONCLUSION: In our cohort of patients, almost all patients who
      underwent revision surgery after primary breast augmentation received bigger
      implants. Patients who specifically wished for size change were younger, asked
      for surgery earlier and received larger volumes compared to patients who
      underwent revision surgery for other reasons. LEVEL OF EVIDENCE IV: This journal
      requires that authors assign a level of evidence to each article. For a full
      description of these Evidence-Based Medicine ratings, please refer to the Table
      of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 30276458
TI  - "Dual-Knot Fixation" Technique for Better Stabilization of the Extended
      Columellar Strut Graft with the Anterior Nasal Spine.
AB  - INTRODUCTION: Extended columellar strut graft (ecsg.) is one of the most crucial
      cartilage tissues used especially in secondary rhinoplasties. Stabilization of an
      ecsg. with the anterior nasal spine (ans.) is very important. Regular suture
      placement is the most common practice. Nevertheless, this kind of suture fixation
      may result in sliding of the ecsg. through either side of the ans. Suture
      placement like the figure of eight may prevent sliding of the ecsg. to sides.
      However, the figure of eight suture forces the graft to turn around during its
      fixation. METHOD: I have tried to solve these two problems with a simple still
      better suture technique. After passing the suture through the hole of the ans., a
      stabilization knot is tied over the spine tip. Then passing the suture through
      the lower end of the ecsg. and fixating it with a second knot named as the
      "fixation knot" results in very good stabilization and prevents both side sliding
      and rotation of the graft. This stabilization technique can be called "dual-knot
      fixation" (dkf.). Opening a small notch at the lower tip of the graft may help to
      hide the "stabilization knot" inside the graft which will help to obscure the
      tiny space between the cartilage and the bone, and thus the bonding process
      between the graft and spine would be better. LEVEL OF EVIDENCE V: This journal
      requires that authors assign a level of evidence to each article. For a full
      description of these Evidence-Based Medicine ratings, please refer to Table of
      Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 30276459
TI  - Simultaneous Nipple-Areola Complex Reconstruction Technique: Combination Nipple
      Sharing and Tattooing.
AB  - BACKGROUND: Nipple-areola complex (NAC) reconstruction is the final critical
      process used to achieve breast symmetry, patient satisfaction, and overall
      reconstruction completeness. Here, we introduce our simplified simultaneous NAC
      reconstruction approach with nipple sharing and tattooing that resulted in
      minimal morbidity, high patient satisfaction, and a shortened total
      reconstructive period. METHODS: Patients who underwent simultaneous nipple
      sharing and tattooing between July 2012 and December 2017 after the final
      operative procedure or adjuvant therapy were included. We retrospectively
      evaluated breast reconstruction type, interval between breast and NAC
      reconstruction, mean operation time for simultaneous nipple sharing and
      tattooing, and postoperative complications. Overall patient satisfaction and
      willingness to undergo simultaneous NAC reconstruction again were assessed.
      RESULTS: The mean interval between the final operative procedure or adjuvant
      therapy and NAC reconstruction was 4.4, 4.4, and 6.7 months in non-adjuvant
      patients, those who underwent chemotherapy, and those who underwent radiotherapy,
      respectively. The mean operation time for simultaneous NAC reconstruction was 46
      min. No major complications such as infection or total nipple loss were observed
      regardless of breast reconstruction type at least 6 months postoperatively. The
      average overall satisfaction was 8.0 on a 10-point scale, and 96.9% of patients
      indicated that they would undergo this simultaneous NAC reconstruction again.
      CONCLUSIONS: Our simplified technique of simultaneous nipple sharing and
      tattooing is safe and reliable and features high patient satisfaction rates.
      Additionally, it can be performed in the clinical setting and is convenient for
      patients and surgeons alike since it features a decreased total reconstruction
      period. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level
      of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 30276460
TI  - Smooth Muscle Alpha Actin Immunoexpression (alpha-Sma) and CD-117 Antibody (C
      Kit) in Capsules Formed by Polyurethane Foam-Coated Silicone Implants and with
      Textured Surface: A Study on Rats.
AB  - BACKGROUND: One of the undesirable complications that might occur after breast
      augmentation with silicone implants is capsular contracture. In its etiology, the
      relations between mast cells and myofibroblasts play an important role in
      collagen synthesis. Mast cells are able to activate fibroblasts into
      myofibroblasts, through paracrine secretions, inducing collagen production. The
      objectives of this study were to analyze the myofibroblast concentration through
      the alpha-SMA immunomarker and evaluate the intensity of mast cell expression
      against the C-Kit immunomarker. MATERIAL AND METHOD: Sixty-four Wistar rats were
      used, divided into two groups (polyurethane foam and textured surface) with 32
      animals in each. The animals received silicone implants on the back, below the
      panniculus carnosus, and after the determined period, they were killed and the
      capsules formed around the implants were studied. The capsules were analyzed
      employing the immunohistochemical technique, with the alpha-SMA and C-Kit
      immunomarkers in subgroups of 30, 50, 70 and 90 days. RESULTS: The myofibroblast
      concentration was higher in the polyurethane group when compared to the textured
      group (30 days p = 0.105; 50 days p = 0.247; 70 days p = 0.014 and 90 days p =
      0.536). The intensity of mast cell expression was more pronounced in the
      polyurethane group when compared to the textured group (30 days p = 0.798; 50
      days p = 0.537; 70 days p = 0.094 and 90 days p = 0.536). CONCLUSIONS:
      Polyurethane-coated implants induced higher concentrations of myofibroblasts and
      higher expression of mast cells, when compared to the textured surface implants.
      NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence
      to each article. For a full description of these Evidence-Based Medicine ratings,
      please refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 30276462
TI  - 37 th Annual Meeting of the German Association of Endocrine Surgeons (CAEK) : 37.
      Arbeitstagung der Chirurgischen Arbeitsgemeinschaft Endokrinologie (CAEK)
      November 15 th - 17 th 2018, Neuss, Germany.

PMID- 30276461
TI  - Within-generation and transgenerational plasticity in growth and regeneration of
      a subordinate annual grass in a rainfall experiment.
AB  - Precipitation changes may induce shifts in plant species or life form dominance
      in ecosystems, making some previously subordinate species abundant. The
      plasticity of certain plant functional traits of these expanding subordinate
      species may be one possible mechanism behind their success. In this study, we
      tested if the subordinate winter annual grass Secale sylvestre shows plasticity
      in growth and reproduction in response to altered environment associated with
      field-scale rainfall manipulations (severe drought, moderate drought, and
      watering) in a semiarid grassland, and whether the maternal environment
      influences offspring germination or growth in a subsequent pot experiment.
      Compared to control plots, S. sylvestre plants grew 38% taller, and produced 32%
      more seeds in severe drought plots, while plants in watered plots were 17%
      shorter, and had 22% less seeds. Seed mass was greatest in severe drought plots.
      Plants growing in drought plots had offspring with enhanced juvenile shoot growth
      compared to the progeny whose mother plants grew in watered plots. These
      responses are most likely explained by the decreased cover of previously dominant
      perennial grasses in severe drought plots, which resulted in wetter soil compared
      to control and watered plots during the peak growth of S. sylvestre. We conclude
      that the plasticity of this subordinate annual species in response to changing
      environment may help to gain dominance with recurring droughts that suppress
      perennial grasses. Our results highlight that exploring both within-generation
      and transgenerational plasticity of subordinate species may lead to a better
      prediction of changes in plant species dominance under climate change.

PMID- 30276463
TI  - Transcriptional repression of CDC6 and SLD2 during meiosis is associated with
      production of short heterogeneous RNA isoforms.
AB  - Execution of the meiotic and mitotic cell division programs requires distinct
      gene expression patterns. Unlike mitotic cells, meiotic cells reduce ploidy by
      following one round of DNA replication with two rounds of chromosome segregation
      (meiosis I and meiosis II). However, the mechanisms by which cells prevent DNA
      replication between meiosis I and meiosis II are not fully understood. Here, we
      show that transcriptional repression of two essential DNA replication genes, CDC6
      and SLD2, is associated with production of shorter meiosis-specific RNAs
      containing the 3' end of both genes. Despite the short CDC6 RNA coding for a
      short protein (Cdc6short), this protein is not essential for meiosis and it does
      not have either a positive or negative impact on DNA replication. Production of
      CDC6short mRNA does not require the upstream CDC6 promoter (PCDC6) and is not a
      processed form of the full-length RNA. Instead, CDC6short depends on
      transcription initiation from within the ORF upon repression of PCDC6. Finally,
      using CDC6 genes from related yeast, we show that repression of full-length CDC6
      mRNA is evolutionarily conserved and that this repression is consistently
      associated with production of unique short CDC6 RNAs. Together, these data
      demonstrate that meiotic cells transcriptionally repress full-length CDC6 and
      SLD2, and that inactivation of PCDC6 results in heterogeneous transcription
      initiation from within the CDC6 ORF.

PMID- 30276464
TI  - Gastrointestinal juvenile-like (inflammatory/hyperplastic) mucosal polyps in
      neurofibromatosis type 1 with no concurrent genetic or clinical evidence of other
      syndromes.
AB  - Gastrointestinal "juvenile-like (inflammatory/hyperplastic) mucosal polyps"
      (JLIHMPs) have been proposed as a neurofibromatosis type 1 (NF1)-specific
      gastrointestinal manifestation. Juvenile polyposis syndrome (JPS) has also been
      reported in a NF1 patient, harboring concurrent NF1 and SMAD4 germline mutations.
      Additionally, NF1-like cafe-au-lait spots have been described in biallelic
      mismatch repair deficiency, another condition featuring gastrointestinal polyps.
      The SMAD4 and BMPR1A genes that are involved in 50-60% of JPS cases have not been
      investigated in the ~ 20 published cases of NF1-associated JLIHMPs with the
      exception of the abovementioned patient with concomitant JPS and NF1. NF1 defects
      have been found in the only two cases exhaustively tested. Therefore, JLIHMP has
      been questioned as an independent, NF1-specific entity. Incidental associations
      between NF1 and gastrointestinal polyposes at risk for gastrointestinal carcinoma
      should not be overlooked, given their implications in terms of clinical
      surveillance. We describe two patients featuring JLIHMPs in
      clinically/genetically proven NF1, in the absence of SMAD4 and BMPR1A mutations.
      In one case, the intervening mucosa was markedly inflamed, unlike JPS. We suggest
      that JLIHMP probably represents a gastrointestinal lesion specific to NF1.

PMID- 30276466
TI  - Safety and efficacy of preoperative chemotherapy followed by esophagectomy versus
      upfront surgery for resectable esophageal squamous cell carcinoma.
AB  - PURPOSE: Neoadjuvant chemotherapy (NAC) followed by esophagectomy has become a
      standard treatment for esophageal squamous cancer (ESCC) in Japan. We used
      propensity-matching analysis to clarify the safety and efficacy of NAC in daily
      clinical practice. METHODS: We reviewed the medical records of 335 patients with
      clinical Stage II/III ESCC diagnosed between 2007 and 2012, including 191 who
      received preoperative NAC (NAC group) and 144 treated by upfront surgery (US
      group). After propensity score matching, there were 118 patients in each group.
      We compared the postoperative complications and long-term outcomes between the
      groups. RESULTS: Seven patients in the NAC group underwent replacement therapy.
      Complications occurred in 76 (68.5%) and 76 (64.4%) patients in NAC and US
      groups, respectively (p = 0.51), and severe complications occurred in 17 (22.4%)
      and 30 (39.5%) patients, respectively (p = 0.057). One (0.8%) and three patients
      (2.5%) from the US group died within 30 days and 90 days after surgery,
      respectively, but none of the patients from the NAC group died within the same
      period. The 5-year survival rate was 54.9% in the NAC group and 41.2% in the US
      group (p = 0.024). CONCLUSIONS: NAC is a safe and effective treatment to improve
      prognosis in the clinical setting.

PMID- 30276467
TI  - Treatment results for lumbar epidural lipomatosis: Does fat matter?
AB  - PURPOSE: The lumbar epidural lipomatosis (LEL) is a rare disease that can cause
      sciatic pain syndrome or neurological deficits comparable to symptoms caused by a
      classical spinal canal stenosis. In severe cases surgical decompression was
      conducted. However, the outcome after decompressive surgery has only been
      investigated in small case series. In this study we compared the outcome of LEL
      patients after microsurgery with the outcome of patients with classical spinal
      stenosis (CSS). METHODS: Patients with LEL (n = 38) and patients with CSS (n =
      51), who received microsurgical decompression, were followed in a prospective
      observational study for 3 years. The clinical results including the Oswestry
      Disability Index, Numeric Pain Rating Scale (NRS), Roland and Morris Disability
      Questionnaire, the Short Form-36 Score and the Walking Distance were analysed and
      compared between both groups. RESULTS: Patients with LEL improved significantly
      after microsurgical decompression in a 3-year follow-up concerning back pain, leg
      pain and pain-associated disability equal to patients with CSS
      (NRSback_LEL_preop. = 6.4; NRSback_CSS_preop. = 6.3; NRSback_LEL_3-years = 3.2;
      NRSback_CSS_3-years = 3.6; NRSleg_LEL_preop. = 6.3; NRSleg_CSS_preop. = 6.5;
      NRSleg_LEL_3-years = 2.5; NRSleg_CSS_3-years = 2.9; ODILEL_preop. = 52.7;
      ODICSS_preop = 51.8; ODILEL_3-years = 32.3; ODICSS_3-years = 27.6). The
      microsurgical decompression had a positive effect on the health-related quality
      of life, and patient satisfaction was high in both groups (LEL group-71%, CSS
      group-69%). CONCLUSIONS: LEL can influence the quality of life dramatically and
      cause a high degree of disability. A surgical decompression is a safe and
      effective procedure with a good clinical outcome comparable to the results in
      patients with an osteoligamentous spinal stenosis. Therefore, microsurgical
      decompression can be recommended in patients with LEL if conservative treatment
      fails. These slides can be retrieved under Electronic Supplementary Material.

PMID- 30276465
TI  - Tau filaments from multiple cases of sporadic and inherited Alzheimer's disease
      adopt a common fold.
AB  - The ordered assembly of tau protein into abnormal filaments is a defining
      characteristic of Alzheimer's disease (AD) and other neurodegenerative disorders.
      It is not known if the structures of tau filaments vary within, or between, the
      brains of individuals with AD. We used a combination of electron cryo-microscopy
      (cryo-EM) and immuno-gold negative-stain electron microscopy (immuno-EM) to
      determine the structures of paired helical filaments (PHFs) and straight
      filaments (SFs) from the frontal cortex of 17 cases of AD (15 sporadic and 2
      inherited) and 2 cases of atypical AD (posterior cortical atrophy). The high
      resolution structures of PHFs and SFs from the frontal cortex of 3 cases of AD, 2
      sporadic and 1 inherited, were determined by cryo-EM. We also used immuno-EM to
      study the PHFs and SFs from a number of cortical and subcortical brain regions.
      PHFs outnumbered SFs in all AD cases. By cryo-EM, PHFs and SFs were made of two C
      shaped protofilaments with a combined cross-beta/beta-helix structure, as
      described previously for one case of AD. The higher resolution structures
      obtained here showed two additional amino acids at each end of the protofilament.
      The immuno-EM findings, which indicated the presence of repeats 3 and 4, but not
      of the N-terminal regions of repeats 1 and 2, of tau in the filament cores of all
      AD cases, were consistent with the cryo-EM results. These findings show that
      there is no significant variation in tau filament structures between individuals
      with AD. This knowledge will be crucial for understanding the mechanisms that
      underlie tau filament formation and for developing novel diagnostics and
      therapies.

PMID- 30276469
TI  - Association between delivery of small-for-gestational age neonate and long-term
      pediatric ophthalmic morbidity.
AB  - OBJECTIVE: To investigate whether delivery of small for gestational age (SGA)
      neonate poses a risk for subsequent long-term ophthalmic morbidity. METHODS: In
      this population-based study, all deliveries between 1991 and 2014 were included.
      Congenital malformations and multiple gestations were excluded from the analysis.
      Offspring were defined as either SGA (weight below the 5th percentile for
      gestational age) or non-SGA. Comparison was performed regarding the incidence of
      long-term ophthalmic morbidity in a cohort of neonates who were born SGA and
      those who were not. Ophthalmic morbidity was documented during any encounter with
      the hospital for a period of up to 18 years after delivery. Ophthalmic morbidity
      included infections of the eye or the adnexa, inflammation of any cause requiring
      admission, visual disturbances, and other hospital admissions carrying an ICD-9
      code of ophthalmic designation. A Cox proportional hazards model was used to
      estimate the adjusted hazards ratio (HR) for ophthalmic morbidity During the
      study period, 243,682 deliveries met the inclusion criteria, of which 11,290
      (4.63%) were defined as SGA. RESULTS: During the follow-up period, SGA neonates
      had higher rates of ophthalmic-related hospitalizations (1.2% versus 1.0%; OR =
      1.22, 95% CI 1.02-1.46; p = 0.026). In a Cox proportional hazards model, adjusted
      for confounders such as maternal age, gestational age at delivery, child birth
      year, low 5 min Apgar scores (< 7), gestational diabetes, maternal hypertensive
      disorders, placental abruption and placenta previa, SGA neonate was independently
      associated with subsequent long-term ophthalmic morbidity (adjusted HR = 1.22;
      95% CI 1.02-1.47; p = 0.024). CONCLUSION: Delivery of an SGA neonate is an
      independent risk factor for long-term ophthalmic morbidity.

PMID- 30276468
TI  - Assessment of long-term intraocular lens (IOL) decentration and tilt in eyes with
      pseudoexfoliation syndrome (PES) following cataract surgery.
AB  - BACKGROUND: To evaluate long-term intraocular lens (IOL) decentration and tilt in
      eyes with pseudoexfoliation syndrome (PES) following cataract surgery using
      Visante anterior segment OCT and iTrace Visual Function Analyzer. METHODS: Sixty
      four eyes following cataract surgery from 2009 to 2012 were included, 34 eyes had
      PES and 30 eyes did not show PES. A standard phacoemulsification procedure
      followed by IOL implantation was performed and patients were followed 4-6 years
      after surgery (mean = 69 months). Best-corrected visual acuity (BCVA),
      capsulorhexis size, and intraocular pressure (IOP) were measured. IOL
      decentration and IOL tilt were evaluated using Visante Omni anterior segment OCT
      (Carl Zeiss Jena GmBH, Germany). The iTrace VFA (Visual Function Analyzer, Hoya
      surgical optics) was used to measure corneal, internal, and total optical
      aberrations. RESULTS: Measurements with iTrace showed that horizontal coma was
      significantly different between PES and control eyes (p = 0.037). Horizontal as
      well as vertical tilt showed a significant difference between PES and control
      eyes (p = 0.035 and p = 0.039). Tilt correlated with capsulorhexis size in PES
      patients (p = 0.011). This indicates a forward tilt of the superior edge of the
      IOL in eyes with PES. CONCLUSIONS: Patients affected by PES seem to have a higher
      risk for long-term complications and changes in visual perception due to IOL tilt
      and decentration after cataract surgery.

PMID- 30276470
TI  - Spatiotemporal activities of Douglas-fir BiP Pro1 promoter in transgenic potato.
AB  - MAIN CONCLUSION: The PmBiPPro1 promoter of the luminal binding protein (BiP) from
      Douglas-fir is fully functional in transgenic potato, responsive to wounding, and
      has high transcriptional activity in tubers. A predefined pattern and level of
      transgene expression targeted to specific tissues or organs and at a particular
      developmental stage is a pre-requisite for the successful development of plants
      with desired traits. Here, we evaluated the transcriptional activity of the
      PmBiPPro1 promoter of the luminal binding protein (BiP) from Douglas-fir, by
      expressing reporter beta-D-glucuronidase (GUS) gene constructs containing three
      different PmBiPPro1 promoter versions (2258 bp, 1259 bp, and 278 bp) in
      transgenic potato. In conifers, this promoter regulates the endoplasmic reticulum
      (ER) molecular chaperon of the HSP70 stress-related protein family and is
      essential for proper functioning of the ER. Stable expression analysis
      demonstrated that two of three PmBiPPro1 promoter versions (PmBiPPro1-1 and
      PmBiPPro1-3) were fully functional in the heterologous host, exhibited high
      transcriptional activities in the leaves of unstressed potatoes, and were
      responsive to wounding. Deletion analysis showed that the positive cis-active
      regulatory elements necessary for higher level expression resided within the -
      1243 to - 261 region, whereas negative cis-active elements encompassed
      nucleotides - 2242 to - 1243. Histochemical staining revealed high level of GUS
      activities in tissues associated with a high rate of cell division and secretory
      activities. Most importantly, the PmBiPPro1 promoters, especially the full-length
      version, had activity in microtubers at a level that was much higher than in any
      other potato organ or tissue. The - 2242 to - 1243 bp region likely contains
      important cis element(s) that interact with tuber-specific transcription factors
      required for promoter activation in the storage organs. The organ-specific
      activity of the PmBiPPro1 promoters may be useful for targeted expression of
      heterologous molecules in potato tubers.

PMID- 30276471
TI  - A review of the seed biology of Paeonia species (Paeoniaceae), with particular
      reference to dormancy and germination.
AB  - MAIN CONCLUSION: Most Paeonia species have epicotyl dormancy. Germination of
      peony seeds requires warm stratification for embryo growth and radicle protrusion
      followed by cold stratification for epicotyl growth. The genus Paeonia
      (Paeoniaceae) includes many popular ornamentals, has colorful flowers and
      contains several Chinese medicinal species. The germination protocol for seeds of
      Paeonia species is complex and impedes the breeding of new cultivars and
      contributes to the rarity and high cost of the plants. Although numerous reports
      on seed dormancy/germination in peonies are scattered throughout the literature,
      most of them are in Chinese. The primary aims of this paper are to provide a
      general overview of the available information on seed dormancy/germination in
      peonies and to make some suggestions regarding propagation for the peony industry
      and breeders. Most Paeonia species have epicotyl dormancy. The embryo is
      differentiated into organs, but it is underdeveloped (small) and must grow inside
      the seed before the radicle can emerge. Germination of peony seeds requires warm
      stratification for embryo growth and radicle protrusion followed by cold
      stratification for epicotyl growth. In addition, the epicotyl is sensitive to
      cold stratification only after the root has grown to a certain length. GA3
      treatment enhances embryo growth and subsequent germination percentages. Further
      investigations on the physiology, genetics and proteomics would contribute to a
      better understanding of seed dormancy in Paeonia.

PMID- 30276472
TI  - Occurrence of the black yeast Hortaea werneckii in the Mediterranean Sea.
AB  - The occurrence of cultivable fungi was investigated along the water column (25
      2500 m depth) of four off-shore stations in the Mediterranean basin. An
      unexpected high abundance of fungi, accompanied by a scarce biodiversity, was
      observed up to 2500 m depth. The black yeast Hortaea werneckii, known to be one
      of the most salt tolerant eukaryotic organisms, was isolated for the first time
      from the Mediterranean Sea, and it was the dominant fungus present in seawater in
      almost all stations and depths, suggesting its ubiquitous distribution. Isolation
      of cultivable strains allowed their phylogenetic and taxonomic characterization,
      and demonstrated that almost all the retrieved fungal species should be
      considered of terrestrial origin, but well adapted to survive and reproduce at
      temperature and salinity conditions of the Mediterranean seawater.

PMID- 30276473
TI  - Emotional talk of patients with breast cancer during review appointments with
      therapeutic radiographers: effects on fears of cancer recurrence.
AB  - : Fears of cancer recurrence (FCR) in patients with breast cancer may develop
      during radiotherapy. Radiographer communication with their patients may influence
      early survivorship FCR level. AIM: To investigate the management of emotional
      talk in patients with breast cancer attending their initial review appointments
      during radiotherapy and predict FCR at 6-8 weeks follow-up. METHODS: A mixed
      methods observational study was conducted. Patients (consecutive sample, n = 60)
      with breast cancer, attending a major Scottish cancer centre, had their first two
      review appointments with their therapeutic radiographer (TR) audio-recorded. In
      addition, FCR was assessed (FCR7) at baseline and at 6-8 weeks following their
      final radiotherapy visit. Two TRs participated. Audio files were coded by the VR
      CoDES system to identify emotional cues and therapeutic radiographer (TR)
      responses. Linear regression models were tested for fit and to identify factors
      associated with follow-up FCR, i.e. patient cues, responses by TR. RESULTS:
      Follow-up FCR was predicted negatively (robust estimator, p = .01) by level of
      patient emotional talk at the second review session. The provision of space by
      the TR, at the second session, to enable patients to expand their emotional
      utterances was also associated, but negatively (p = .01), with follow-up FCR.
      These effects were maintained after inclusion of covariates: age, treatment
      received and living conditions. CONCLUSIONS: Patient's emotional expression and
      TR responses at the second review meeting predicted follow-up FCR. The study
      shows the effect of communication processes on this specific distress component
      of the patient's survivorship experience. TRIAL REGISTRATION: NCT02599506.

PMID- 30276474
TI  - Balneotherapy in chronic inflammatory rheumatic diseases-a narrative review.
AB  - Since ancient time, thermal baths and mudpacks have been used as treatments for
      rheumatic diseases and other musculoskeletal complaints. Despite basic researches
      suggest an anti-inflammatory effect of spa therapy, there is no consensus about
      the benefits of balneotherapy in patients with chronic inflammatory rheumatic
      diseases. The aim of this review is to summarize the currently available
      information on clinical effects of balneotherapy in these diseases. We did a
      literature search for articles considering the randomized controlled trials
      (RCTs) published until today. Although many selected studies do not have an
      elevated methodological quality, data from these RCTs support a beneficial effect
      of spa therapy. Balneotherapy highly improves the clinical course of the disease
      in patients with predominant axial involvement, such as with ankylosing and
      enteropathic spondylitis; the effects are less favorable in patients with
      predominant peripheral articular inflammation, such as rheumatoid arthritis. Good
      results have been observed in patients with psoriatic arthritis, but only few
      RCTs have been conducted on this disease. Spa therapy appears safe, and adverse
      events have been reported only in a few patients.

PMID- 30276475
TI  - Impact of climate on the population dynamics of an alpine ungulate: a long-term
      study of the Tatra chamois Rupicapra rupicapra tatrica.
AB  - Global warming is considered as a phenomenon having a negative effect on animals
      living in cold climate. However, herbivorous species inhabiting cold zones may
      potentially benefit from increase of temperature as this influence duration of
      vegetation period and increase food resources. In this study, we analyze the
      impact of climate factors on the long-term dynamics of an isolated and unhunted
      population of the Tatra chamois Rupicapra rupicapra tatrica. The population
      growth rate, based on autumnal chamois counting carried out from 1957 to 2016,
      were correlated with a set of climatic variables. We tested the hypothesis that
      high temperatures in summer could have a positive impact on the population, since
      they influence vegetation growth, which ensure food resources. On the other hand,
      heavy falls of snow and long-lasting and deep snow cover could adversely affect
      the population by reducing population survival during the winter. The results of
      this study indicate that climatic variables best explaining the autoregressed
      population growth rate (from the autumn of year t-1 to the autumn of year t) were
      the mean summer temperature of year t-1: the population increase was greater
      following a warmer summer in year t-1 and, in lower extent, the total
      precipitation during winter: the population decrease was greater following a
      winter with heavy snowfall. Duration and thickness of snow cover have no negative
      effect on population growth rate. The results indicate that the population
      dynamic of the Tatra chamois is determined in the long term by weather
      conditions, mainly by temperature, when kids are birthing and growing. The
      results of this work highlight that climatic changes may be responsible for the
      population dynamic of high-mountain species. Climate warming may lead to increase
      in duration of vegetation period in cold climatic zones, what may in turn have
      positive effect on herbivorous species, which relay upon food resources limited
      by low temperatures within vegetation period.

PMID- 30276477
TI  - Childhood adversity and sleep are associated with symptom severity in perinatal
      women presenting for psychiatric care.
AB  - This study leverages psychiatric intake data from treatment-seeking perinatal
      women aiming to explore the understudied associations between childhood
      adversity, sleep quality, and severity of perinatal mental illness in this
      population. The sample is 578 perinatal women presenting for initial evaluation
      to a university-based perinatal psychiatry clinic. At intake, we collected
      demographics, adverse childhood experiences (ACEs), sleep quality, and diagnosis
      and symptom severity of depression, anxiety, and posttraumatic stress disorder
      (PTSD). Clinician-rated diagnoses showed that 65% of women met criteria for major
      depression, 23% for generalized anxiety disorder and 4% for PTSD; almost 30% of
      women had childhood adversity and 98.2% reported poor perinatal sleep quality.
      Regression analyses revealed differential associations between ACEs and sleep
      quality and perinatal mood symptoms; ACEs were significantly associated with
      pregnancy and postpartum PTSD, whereas sleep quality was associated with
      perinatal depression and generalized anxiety. Screening for ACEs and sleep
      quality during perinatal intake has high clinical utility, as these two factors
      significantly contribute to symptom severity across peripartum.

PMID- 30276476
TI  - Dietary curcumin supplementation does not alter peripheral blood mononuclear cell
      responses to exertional heat stress.
AB  - INTRODUCTION: Curcumin reduces gut barrier damage and plasma cytokine responses
      to exertional heat stress. However, the role of peripheral blood mononuclear cell
      (PBMC) in this response remains unclear. PURPOSE: This work investigated the
      effect of 3 days of 500 mg/day dietary curcumin supplementation on PBMC responses
      to exertional heat stress in non-heat acclimated humans. METHODS: Eight
      participants ran (65% VO2max) for 60 min in an environmental chamber (37  degrees
      C/25% RH) two times (curcumin/placebo). Blood samples were collected pre, post, 1
      h post, and 4 h post-exercise. PBMC were isolated from blood samples and the
      protein content of markers along the TLR4 signaling pathway (TLR4, MyD88, pNF
      kappaB, NF-kappaB), indicators of cellular energy status (SIRT1 and p-AMPK), and
      mediators of cellular heat shock response (pHSF-1 and HSP70) were examined with
      Western blot. Data were analyzed with two-way (condition * time) RM-ANOVAs with
      Newman-Keuls post hocs. RESULTS: As compared to placebo, curcumin did not alter
      protein expression in PBMC (p > 0.05). However, in both study conditions at 1 h
      post-reductions were noted in TLR 4 (- 21.5%; p = 0.03), HSP70 (- 11.0%; p =
      0.04), pAMPK (- 48.5%; p < 0.01), and SIRT1 (- 47.8%; p < 0.01). Remarkably, the
      ratio of pNF-kappaB to NF-kappaB was elevated in both conditions at this same
      timepoint (+ 75.4%; p = 0.02). CONCLUSIONS: Inflammatory protein expression in
      PBMC did not differ between curcumin and placebo conditions. Downregulation of
      pAMPK/SIRT1 and release of HSP70 to the bloodstream may compensate for reduced
      TLR4, allowing PBMC to maintain inflammatory capacity and preventing an "open
      window" during the hours following hyperthermic exercise.

PMID- 30276478
TI  - Long-term vitamin-K antagonist use and coronary artery calcification.
AB  - BACKGROUND: The aim of this study was to investigate the impact of vitamin K
      antagonist (VKA) therapy on coronary artery calcification (CAC) by comparing long
      term VKA users with metallic prosthetic valves (MPVs) and VKA-free patients
      undergoing coronary calcium scoring for cardiovascular (CV) risk stratification.
      METHODS: A total of 108 patients (43 VKA users with MPV and 65 gender-, age-, and
      risk-factor-matched VKA-free patients) were included in the study. CAC was
      determined via computed tomography (CT) and quantified on the basis of the
      Agatston score. The VKA group comprised patients who had an MPV for longer than 5
      years, which entailed long-term VKA use. RESULTS: Long-term VKA users had more
      calcified coronary arteries compared with the control group (178.1 +/- 278 vs.
      61.1 +/- 130.6, p = 0.01). There was no difference between groups in terms of
      traditional CV risk factors. The mean duration of VKA use was 15 +/- 7 years for
      the patients with MPV. There was no correlation between the duration of VKA use
      and mean Agatston score (r = 0.2, p = 0.215). CONCLUSION: With its unique
      selection of patient groups, our study extends the findings of previous research
      that long-term VKA use is related to CAC as detected via CT scanning. The longer
      and more potent VKA regimen required for MPV patients is the primary cause of CAC
      in this group.

PMID- 30276479
TI  - Clinical outcomes after tricuspid surgery : The role of previous cardiac surgery.
AB  - BACKGROUND: The aim of our study was to assess the outcomes of surgical treatment
      for severe tricuspid regurgitation according to whether cardiac surgery had been
      performed before the tricuspid valve intervention. METHODS: Between 1996 and
      2013, 201 consecutive patients with severe tricuspid regurgitation underwent
      tricuspid surgery at our center. Patients were classified according to whether or
      not they had undergone previous cardiac surgery, which 33% of the sample had.
      Perioperative as well as long-term morbidity and mortality were analyzed.
      RESULTS: Mean patient age was 62.3 years. 32.8% underwent suture annuloplasty,
      41.3% underwent ring annuloplasty, 15.4% received a bioprosthesis, and 10.4%
      received a mechanical prosthesis. There were no significant differences in
      perioperative mortality between the group that had not undergone previous cardiac
      surgery and the group that had (12.7% vs. 17.9%, respectively; p = 0.32). The
      long-term mortality rate (median follow-up time: 53 months) was 43.3%. Long-term
      survival curves showed no significant differences between the two groups (p =
      0.884), and previous cardiac surgery was not a predictive factor for long-term
      mortality (hazard ratio = 1.211; p = 0.521). CONCLUSION: In a series of patients
      who underwent tricuspid valve surgery, no significant differences were observed
      in perioperative mortality or in long-term survival according to whether or not
      subjects had undergone previous cardiac surgery.

PMID- 30276480
TI  - Head and Neck Cancer: Improving Patient-Reported Outcome Measures for Clinical
      Practice.
AB  - OPINION STATEMENT: Head and neck cancer includes a wide range of tumors that
      occur in several areas of the upper aerodigestive tract. Most head and neck
      cancer patients report treatment-related late effects (both physical and psycho
      social). High-quality and patient-centered care in head and neck cancer depend on
      the understanding of the continuum patient's experience-the disease pathway.
      Healthcare has been improved by involving patients more actively in the disease
      process, and a few reports support that patient-reported outcomes-built around
      the patient's experience-given in a timely manner to oncologists are extremely
      valuable in oncology clinical care. Implementation and clinical use of patient
      reported outcomes requires some procedures involving head and neck cancer
      patients, clinicians, researchers, and institutional leaders The unified and
      integrated vision is still absent and some current concerns are being discussed
      to optimize benefits of patient-reported outcomes use in clinical practice. The
      inclusion of all first-line caregivers, team formation and training, continuous
      monitoring improvement, and analysis are critical success factors to consider.
      Our team developed a broader and inclusive understanding of patient-reported
      outcomes. Patient-reported outcome (Health-Related Quality of Life) assessment is
      implemented as a systematic and routine process in Head and Neck Unit. Head and
      neck cancer patients consider the questionnaire administration as part of the
      clinical approach. We are currently working in a program (PROimp) using
      mathematical models to identify common head and neck cancer patterns and building
      prognostic predictive models, to predict future outcomes, to appraise
      risk/benefit of treatments (standard or new), and to estimate patient's risk of
      future disease development. It is our aim to better comprehend the singular and
      unexpected perceptions to really provide directed and personalized cancer care
      defining the patient pathway. The future holds promising for PROs that are
      ascending as a nuclear outcome in head and neck oncology.

PMID- 30276481
TI  - The biotechnological potential of anaerobic fungi on fiber degradation and
      methane production.
AB  - Anaerobic fungi (phylum Neocallimastigomycota), an early branching family of
      fungi, are commonly encountered in the digestive tract of mammalian herbivores.
      To date, isolates from ten described genera have been reported, and several novel
      taxonomic groupings are detected using culture-independent molecular methods.
      Anaerobic fungi are recognized as playing key roles in the decomposition of
      lignocellulose (up to 50% of the ingested and untreated lignocellulose), with
      their physical penetration and extracellular enzymatical secretion of an unbiased
      diverse repertoire of cell-wall-degrading enzymes. The secreted cell-wall
      degrading enzymes of anaerobic fungi include both free enzymes and extracellular
      multi-enzyme complexes called cellulosomes, both of which have potential as fiber
      degraders in industries. In addition, anaerobic fungi can provide large amounts
      of substrates such as hydrogen, formate, and acetate for their co-cultured
      methanogens. Consequently, large amounts of methane can be produced. And thus, it
      is promising to use the co-culture of anaerobic fungi and methanogens in the
      biogas process to intensify the biogas yield owing to the efficient and robust
      degradation of recalcitrant biomass by anaerobic fungi and improved methane
      production from co-cultures of anaerobic fungi and methanogens.

PMID- 30276483
TI  - Biodegradable nanoprobe based on MnO2 nanoflowers and graphene quantum dots for
      near infrared fluorescence imaging of glutathione in living cells.
AB  - Near infrared (NIR) emitting semiconductor quantum dots can be excellent
      fluorescent nanoprobes, but the poor biodegradability and potential toxicity
      limits their application. The authors describe a fluorescent system composed of
      graphene quantum dots (GQDs) as NIR emitters, and novel MnO2 nanoflowers as the
      fluorescence quenchers. The system is shown to be an activatable and
      biodegradable fluorescent nanoprobe for the "turn-on" detection of intracellular
      glutathione (GSH). The MnO2-GQDs nanoprobe is obtained by adsorbing GQDs onto the
      surface of MnO2 nanoflowers through electrostatic interaction. This results in
      the quenching of the NIR fluorescence of the GQDs. In the presence of GSH, the
      MnO2-GQDs nanoprobe is degraded and releases Mn2+ and free GQDs, respectively.
      This gives rise to increased fluorescence. The nanoprobe displays high
      sensitivity to GSH and with a 2.8 MUM detection limit. It integrates the
      advantages of NIR fluorescence and biodegradability, selectivity,
      biocompatibility and membrane permeability. All this makes it a promising
      fluorescent nanoprobe for GSH and for cellular imaging of GSH as shown here for
      the case of MCF-7 cancer cells. Graphical abstract A biodegradable NIR
      fluorescence nanoprobe (MnO2-GQDs) for the "turn-on" detection of GSH in living
      cell was established, with the NIR GQD as the fluorescence reporter and the MnO2
      nanoflower as the fluorescence quencher.

PMID- 30276484
TI  - Electrochemical determination of dopamine and uric acid using a glassy carbon
      electrode modified with a composite consisting of a Co(II)-based metalorganic
      framework (ZIF-67) and graphene oxide.
AB  - A composite was prepared from a Co(II)-based zeolitic imidazolate framework (ZIF
      67) and graphene oxide (GO) by an in situ growth method. The material was
      electrodeposited on a glassy carbon electrode (GCE). The modified GCE was used
      for the simultaneous voltammetric determination of dopamine (DA) and uric acid
      (UA), typically at working potentials of 0.11 and 0.25 V (vs. SCE). The
      morphology and structure of the nanocomposite were characterized by scanning
      electron microscopy, transmission electron microscopy, Fourier transform infrared
      spectroscopy and X-ray diffraction. The modified electrode exhibits excellent
      electroanalytical performance for DA and UA owing to the synergistic effect of
      the high electrical conductivity of GO and the porosity of ZIF-67. By applying
      differential pulse voltammetry, a linear response is found for DA in the 0.2 to
      80 MUM concentration range, and for UA between 0.8 and 200 MUM, with detection
      limits of 50 and 100 nM (at S/N = 3), respectively. Further studies were
      performed on the effect of potential interferents, and on electrode stability and
      reproducibility. The modified GCE was applied to the simultaneous detection of DA
      and UA in spiked human urine and gave satisfying recoveries. Graphical abstract
      Schematic of the preparation procedure of GO-ZIF67 and electrochemical reaction
      mechanisms of UA and DA at the GO-ZIF67-modified glassy carbon electrode (GCE).
      GO: graphene oxide; ZIF-67: Co(II)-based zeolitic imidazolate framework.

PMID- 30276482
TI  - Molecular characterization of putative neuropeptide, amine, diffusible gas and
      small molecule transmitter biosynthetic enzymes in the eyestalk ganglia of the
      American lobster, Homarus americanus.
AB  - The American lobster, Homarus americanus, is a model for investigating the
      neuromodulatory control of physiology and behavior. Prior studies have shown that
      multiple classes of chemicals serve as locally released/circulating
      neuromodulators/neurotransmitters in this species. Interestingly, while many
      neuroactive compounds are known from Homarus, little work has focused on
      identifying/characterizing the enzymes responsible for their biosynthesis,
      despite the fact that these enzymes are key components for regulating
      neuromodulation/neurotransmission. Here, an eyestalk ganglia-specific
      transcriptome was mined for transcripts encoding enzymes involved in
      neuropeptide, amine, diffusible gas and small molecule transmitter biosynthesis.
      Using known Drosophila melanogaster proteins as templates, transcripts encoding
      putative Homarus homologs of peptide precursor processing (signal peptide
      peptidase, prohormone processing protease and carboxypeptidase) and immature
      peptide modifying (glutaminyl cyclase, tyrosylprotein sulfotransferase, protein
      disulfide isomerase, peptidylglycine-alpha-hydroxylating monooxygenase and
      peptidyl-alpha-hydroxyglycine-alpha-amidating lyase) enzymes were identified in
      the eyestalk assembly. Similarly, transcripts encoding full complements of the
      enzymes responsible for dopamine [tryptophan-phenylalanine hydroxylase (TPH),
      tyrosine hydroxylase and DOPA decarboxylase (DDC)], octopamine (TPH, tyrosine
      decarboxylase and tyramine beta-hydroxylase), serotonin (TPH or tryptophan
      hydroxylase and DDC) and histamine (histidine decarboxylase) biosynthesis were
      identified from the eyestalk ganglia, as were those responsible for the
      generation of the gases nitric oxide (nitric oxide synthase) and carbon monoxide
      (heme oxygenase), and the small molecule transmitters acetylcholine (choline
      acetyltransferase), glutamate (glutaminase) and GABA (glutamic acid
      decarboxylase). The presence and identity of the transcriptome-derived
      transcripts were confirmed using RT-PCR. The data presented here provide a
      foundation for future gene-based studies of neuromodulatory control at the level
      of neurotransmitter/modulator biosynthesis in Homarus.

PMID- 30276487
TI  - Association of the CYP4V2 polymorphism rs13146272 with venous thromboembolism in
      a Chinese population.
AB  - Genome-wide association studies have identified the CYP4V2 polymorphism
      (rs13146272) as a risk factor associated with venous thromboembolism (VTE).
      However, due to the small sample size and variance in genetic analysis models,
      the relationship between VTE and rs13146272 remains unclear. Here, we performed a
      case-control study to analyse the associations between rs13146272 and VTE in a
      Chinese population and to compare the differences among various ethnicities. In
      this study, 226 VTE patients and 205 healthy controls were recruited, and the
      allele frequency of variant rs13146272 was analysed by a MassARRAY SNP genotyping
      assay. In addition, 9 case-control cohorts from 5 studies involving 6667 VTE
      affected individuals and 8716 control subjects were included in this meta
      analysis. Pooled ORs and 95% CIs were calculated to assess the association
      between rs13146272 and VTE by using different genetic models. Our case-control
      study results showed that there was no significant association between VTE and
      rs13146272 under the additive model (OR = 0.92, 95% CIs: 0.70-1.21, p = 0.55) in
      this Chinese population. However, the results of the meta-analysis performed by
      merging all cohorts showed that rs13146272 was significantly associated with VTE
      under the additive model, recessive model and dominant model. In the additive and
      recessive models, the association reached the threshold for genome-wide
      significance (p < 5.0e-08). In conclusion, our pooled systematic study results
      indicated that individuals with the A allele had a higher risk of developing VTE
      than those with the C allele of the rs13146272 variant, but the risk was
      inconsistent among different ethnicities. Further validation of this association
      with larger sample sizes and multiple ethnicities is warranted.

PMID- 30276485
TI  - Metal and metalloid concentrations in soil, surface water, and vegetables and the
      potential ecological and human health risks in the northeastern area of Hanoi,
      Vietnam.
AB  - Heavy metal and metalloid contamination and related risks for the environment and
      human health are matters of increasing concern. This study assessed metal and
      metalloid concentrations in soil, surface water, and locally grown vegetable to
      assess exposure and related risks for the environment and human health in the
      northeastern rural area of Hanoi. Concentrations of metals and metalloids in
      soils exceeded regulatory thresholds in some locations (e.g., Me Linh and Gia Lam
      districts). The carcinogenic elements As and Cr were identified as a major
      concern with concentrations up to 693 MUg g-1 and 147 MUg g-1, respectively.
      Industrial point sources or groundwater irrigation practices in the intensive
      organic farming areas were identified as potential factors contributing to the
      accumulation of carcinogenic metals and metalloids in topsoil layers. Metal and
      metalloid concentrations detected in water and vegetables were below the
      regulatory threshold levels (WHO guideline and maximum allowable limits). While
      contamination was not observed at a large geographical scale, local soil
      contamination in specific areas of agricultural importance could pose high
      ecological and human health-related risks with unclear long-term impacts. The
      highly carcinogenic soil contamination detected in this study may be a factor
      adding to the increased cancer incidence rate in Hanoi area, as the total
      carcinogenic risk calculated for Hanoi area exceeds the cancer likelihood
      threshold by a factor of 25. Further research is needed to examine potential
      links, and the involvement of both stakeholders and policy makers is needed to
      adequately evaluate the risks for Hanoi area and coordinate future remediation
      plans if risks are justified.

PMID- 30276486
TI  - Examining the Influence of E-Health Education on Professional Practice.
AB  - e-Health is steadily integrating into modern health services, making significant
      changes in the way health services are traditionally delivered. To work in this
      new environment, healthcare workers are required to have new knowledge, skills
      and competencies specific to e-Health. The aim of this study was to understand
      the self-reported perceptions of graduates regarding the influence of an e-Health
      postgraduate program on their professional careers. In addition, this paper will
      provide an overview of the e-Health postgraduate program. All graduates from 2005
      to 2015 were surveyed using an online questionnaire that consisted of a mixture
      of closed and open-ended questions. The number of participants in the study was
      32. Response rate was 62%. The main motivating factors for studying e-Health were
      'relevance to current practice' and 'e-Health is the future'. The participants
      noted that the opportunity to 'acquiring relevant knowledge' and 'having
      exposure' were key benefits offered by the e-Health education program. The
      majority of graduates (n = 23, 72%) thought that the postgraduate e-Health
      program had an influence on their professional practice. A similar number of
      participants (n = 23, 72%) mentioned that they had worked in the field of e
      Health since their graduation. Their professional roles mainly involved
      'implementation of e-Health in health service settings' and the 'use of e-Health
      in clinical practice'. While e-Health may be steadily integrating into modern
      health services, e-Health specific job opportunities are still relatively
      limited. e-Health workforce development must be given priority.

PMID- 30276488
TI  - A multiscale model to predict current absolute risk of femoral fracture in a
      postmenopausal population.
AB  - Osteoporotic hip fractures are a major healthcare problem. Fall severity and bone
      strength are important risk factors of hip fracture. This study aims to obtain a
      mechanistic explanation for fracture risk in dependence of these risk factors. A
      novel modelling approach is developed that combines models at different scales to
      overcome the challenge of a large space-time domain of interest and considers the
      variability of impact forces between potential falls in a subject. The multiscale
      model and its component models are verified with respect to numerical
      approximations made therein, the propagation of measurement uncertainties of
      model inputs is quantified, and model predictions are validated against
      experimental and clinical data. The main results are model predicted absolute
      risk of current fracture (ARF0) that ranged from 1.93 to 81.6% (median 36.1%) for
      subjects in a retrospective cohort of 98 postmenopausal British women (49
      fracture cases and 49 controls); ARF0 was computed up to a precision of 1.92
      percentage points (pp) due to numerical approximations made in the model; ARF0
      possessed an uncertainty of 4.00 pp due to uncertainties in measuring model
      inputs; ARF0 classified observed fracture status in the above cohort with AUC =
      0.852 (95% CI 0.753-0.918), 77.6% specificity (95% CI 63.4-86.5%) and 81.6%
      sensitivity (95% CI 68.3-91.1%). These results demonstrate that ARF0 can be
      computed using the model with sufficient precision to distinguish between
      subjects and that the novel mechanism of fracture risk determination based on
      fall dynamics, hip impact and bone strength can be considered validated.

PMID- 30276489
TI  - Effect of blue LED on the healing process of third-degree skin burns: clinical
      and histological evaluation.
AB  - The aim of this study was to evaluate the effects of blue light-emitting diode
      (LED) on the healing process of third-degree skin burns in rats through clinical
      and histological parameters. Forty male Wistar rats were divided into two groups:
      control (CTR) (n = 20) and blue LED (BLUE) (n = 20), with subgroups (n = 5) for
      each time of euthanasia (7, 14, 21, and 28 days). LED (470 nm, 1 W, 12.5 J/cm2
      per point, 28 s) was applied at four points of the wound (total, 50 J/cm2). Feed
      intake was measured every other day. It was observed that there were no
      statistically significant differences in the Wound Retention Index (WRI) of the
      BLUE group in relation to CTR group (p > 0.05) at the evaluation times. After 14,
      21, and 28 days, it was observed that the animals in the BLUE group consumed more
      feed than animals in the CTR group (p < 0.05). At 7 days, there was a
      statistically significant increase in the angiogenic index (AI) in BLUE (median:
      6.2) when compared to CTR (median: 2.4) (p = 0.01) and all animals in BLUE had
      already started re-epithelialization. This study suggests that blue LED, at the
      dosimetry used, positively contributed in important and initial stages of the
      healing process of third-degree skin burns.

PMID- 30276490
TI  - Q-switched 1064 nm Nd-Yag nanosecond laser effects on skin barrier function and
      on molecular rejuvenation markers in keratinocyte-fibroblasts interaction.
AB  - Skin represents an interface between internal and external environment; it
      protects human body by regulating the water loss and the maintenance of body
      temperature, defending against irritant and pathogen agents, and against
      physical, chemical, and UV damage. It provides to essential physiological
      functions, such as the important antioxidant defense capacity; its
      protective/defensive function is performed by a high number of proteins, and
      shows important functions in maintenance of skin barrier homeostasis.
      Keratinocytes and fibroblasts play a pivotal role to determine or prevent skin
      aging in response to intrinsic or extrinsic stimuli, modulating cytokines and
      several biochemical factors. Non-ablative technologies are playing an increasing
      role in the management of skin aging, inducing a dermal remodeling without a
      visible epidermal damage. The objective of this study was to evaluate the effect
      of Q-switched 1064 Nd-YAG laser (Medlite Conbio C6 Nd-YAG laser, Cynosure USA) in
      skin barrier function, analyzing the constituents which are strongly altered in
      aging skin. Particularly, we evaluated the expression of filaggrin, TGase, HSP70,
      and aquaporins, on HaCaT cells. The expression of proinflammatory cytokines has
      been investigated too.As a second step of the study, we analyzed the modulation
      of the rejuvenation molecular markers on human skin fibroblasts (HDFs) stimulated
      with keratinocytes conditioned medium (KCM).Our results demonstrated that Q
      switched 1064 nm Nd:YAG laser acts on the skin barrier function, increasing the
      expression of aquaporins, filaggrin, TGase, and HSP70, modulating the
      proinflammatory cytokines. In fibroblasts stimulated with keratinocytes
      conditioned medium (KCM) and irradiated with Q-switched 1064 nm Nd:YAG laser, we
      can observe a reduction of MMP-1 and an increase in procollagen, collagen type I,
      and elastin. Our results highlight that Q-switched 1064 nm Nd:YAG laser treatment
      could represent an effective weapon to fight skin aging.

PMID- 30276492
TI  - Lower Limb Posture Affects the Mechanism of Injury in Under-Body Blast.
AB  - Over 80% of wounded Service Members sustain at least one extremity injury. The
      'deck-slap' foot, a product of the vehicle's floor rising rapidly when attacked
      by a mine to injure the limb, has been a signature injury in recent conflicts.
      Given the frequency and severity of these combat-related extremity injuries, they
      require the greatest utilisation of resources for treatment, and have caused the
      greatest number of disabled soldiers during recent conflicts. Most research
      efforts focus on occupants seated with both tibia-to-femur and tibia-to-foot
      angles set at 90 degrees ; it is unknown whether results obtained from these
      tests are applicable when alternative seated postures are adopted. To investigate
      this, lower limbs from anthropometric testing devices (ATDs) and post mortem
      human subjects (PMHSs) were loaded in three different seated postures using an
      under-body blast injury simulator. Using metrics that are commonly used for
      assessing injury, such as the axial force and the revised tibia index, the lower
      limb of ATDs were found to be insensitive to posture variations while the
      injuries sustained by the PMHS lower limbs differed in type and severity between
      postures. This suggests that the mechanism of injury depends on the posture and
      that this cannot be captured by the current injury criteria. Therefore, great
      care should be taken when interpreting and extrapolating results, especially in
      vehicle qualification tests, when postures other than the 90 degrees -90 degrees 
      are of interest.

PMID- 30276491
TI  - Spectrophotometric determination of platelet counts in platelet-rich plasma.
AB  - BACKGROUND: Platelet-rich plasma (PRP) is widely used in regenerative dentistry
      and other medical fields. However, its effectiveness has often been questioned.
      For better evaluation, the quality of individual PRP preparations should be
      assured prior to use. We proposed a spectrophotometric method for determination
      of platelet counts and validated its applicability using two types of PRP
      preparations. METHODS: Blood samples were obtained from healthy male volunteers
      and pure PRP (P-PRP) and leukocytes-rich PRP (L-PRP) were prepared using the
      double-spin method. In serial dilutions, platelet counts in P-PRP and L-PRP were
      determined using an automated hematology analyzer and a compact
      spectrophotometer. For validation, P-PRP and L-PRP independently prepared by
      three well-trained operators were used for comparison of the calculated and
      measured platelet counts. RESULTS: In the two types of PRP samples evaluated,
      platelet counts were almost equal and greater amount of both white blood cells
      (WBCs) and red blood cells (RBCs) were included in L-PRP preparations. The
      calibration curve obtained from serially diluted P-PRP showed a strong
      correlation (R2 = 0.995), whereas that of L-PRP was relatively weaker (R2 =
      0.975). In validation testing, the scatter plot of the calculated platelet counts
      versus the measured values showed a strong correlation in P-PRP (R2 = 0.671),
      whereas that of L-PRP showed a much weaker correlation (R2 = 0.0605).
      CONCLUSIONS: This method can precisely determine platelet counts in PRP
      preparations when the inclusion of WBCs or RBCs is minimized. Therefore, we
      recommend that clinicians use this method for quality assurance of individual PRP
      preparations.

PMID- 30276493
TI  - Long Working Hours and Risk of Cardiovascular Disease.
AB  - PURPOSE OF REVIEW: To summarize the evidence on the relationship between long
      working hours and cardiovascular disease, such as coronary heart disease and
      stroke. RECENT FINDINGS: Large-scale meta-analyses with published and individual
      participant observational data on more than 740,000 men and women free of
      cardiovascular disease report a link between long working hours (>= 55 h a week)
      and the onset of cardiovascular events. Our meta-analytic update of summary
      evidence suggests a 1.12-fold (95% CI 1.03-1.21) increased risk associated with
      coronary heart disease and a 1.21-fold (95% CI 1.01-1.45) increased risk of
      stroke, although the evidence is somewhat inconsistent and the possibility of
      residual confounding and bias cannot be ruled out. Few studies have examined the
      mechanisms which may be stress-related, behavioral, or biological. The recent
      pooled analyses suggest that increased cardiac electric instability and
      hypercoagulability might play a role. The evidence that long working hours are a
      risk factor for cardiovascular disease is accumulating and suggests a small risk.
      Studies on the effects of long working hours in high-risk populations and those
      with pre-existing cardiovascular disease, mechanistic research, and intervention
      studies are needed to advance this research field.

PMID- 30276494
TI  - Household Determinants of Liquified Petroleum Gas (LPG) as a Cooking Fuel in SW
      Cameroon.
AB  - Currently 70% of the population in Cameroon are reliant on solid fuel for cooking
      (90% in rural communities) and the associated household air pollution contributes
      to significant mortality and morbidity in the country. To address the problems of
      energy security, deforestation and pollution the government has developed a
      strategy (Masterplan) to increase use of liquified petroleum gas (LPG) as a
      cooking fuel from 12% to 58% by 2030. As a clean fuel scaled adoption of LPG has
      the potential to make significant positive impacts on population health. The LPG
      Adoption in Cameroon Evaluation (LACE) studies are assessing in the community (i)
      barriers and enablers for and (ii) local interventions to support, adoption and
      sustained use of LPG. A census survey conducted for LACE in rural and peri-urban
      regions of SW Cameroon provided an opportunity to investigate current fuel use
      patterns and factors associated with primary and exclusive use of LPG. A cross
      sectional survey of 1577 households (1334 peri-urban and 243 rural) was conducted
      in March 2016 using standardised fuel use and household socio-demographic
      questions, administered by trained fieldworkers. Wood (40.7%) and LPG (51.1%)
      were the most frequently reported fuels, although the dominant fuels in rural and
      peri-urban communities were wood (81%) and LPG (58%) respectively. Fuel stacking
      was observed for the majority of LPG using households (91% of peri-urban and 99%
      of rural households). In rural homes, a higher level of education, access to
      sanitation and piped water and household wealth (income and asset ownership) were
      all significantly associated with LPG use (p < 0.05). In peri-urban homes,
      younger age, access to sanitation and piped water and increasing education were
      significantly associated with both any and exclusive use of LPG (p < 0.05).
      However, whilst household wealth was related to any LPG use, there was no
      relationship with exclusive use. Results from this census survey of a relatively
      well-established LPG market with lower levels of poverty and high levels of
      education than Cameroon as a whole, find LPG usage well below target levels set
      by the Cameroon government (58% by 2030). Fuel stacking is an issue for the
      majority of LPG using households. Whilst, as observed here, education, household
      wealth and socio-economic status are well recognised predictors of adoption and
      sustained use of clean modern fuels, it is important to consider factors across
      the whole LPG eco-system when developing policies to support their scaled
      expansion. A comprehensive approach is therefore required to ensure
      implementation of the Cameroon LPG Masterplan achieves its aspirational adoption
      target within its stated timeframe.

PMID- 30276496
TI  - Factors related to cervical cancer screening among women of childrearing age: a
      cross-sectional study of a nationally representative sample in Japan.
AB  - BACKGROUND: This study aimed to determine the factors related to undergoing
      cervical cancer screening among Japanese women of childrearing age by focusing on
      the presence or absence of children. METHODS: This was a cross-sectional study of
      a nationally representative sample based on the Comprehensive Survey of Living
      Conditions in Japan. Data for women aged 20-39 were selected, and those whose
      number of children was unknown, whose youngest child was under 2 years or of
      unknown age, who were either hospitalized or institutionalized, and who were
      pregnant were excluded. To determine the factors related to undergoing cervical
      cancer screening, multivariable logistic regression analysis was performed on the
      following variables: status of cervical cancer screening, age, number of
      children, marital status, educational level, cohabitation with parents,
      employment status, subjective health awareness, hospital use, health check-ups,
      subjective symptoms of health, and interaction of women's age and number of
      children. RESULTS: Of the 49,217 women in the analyses, 19,545 (39.7%) underwent
      cervical cancer screening within the last 2 years. Undergoing cervical cancer
      screening increased with advancing age. On comparing women with and without
      children in the same generation, screening rates among women with children were
      higher than those without children in their early 20s, the same in their late
      20s, and lower in their 30s. Receiving health check-ups, higher education,
      subjective symptoms, and hospital use increased participation in cervical cancer
      screening. CONCLUSIONS: Although women of childrearing age tended to undergo
      cervical cancer screening with advancing age, the increase tended to be
      restrained among mothers.

PMID- 30276497
TI  - Alcohol quantity and quality price elasticities: quantile regression estimates.
AB  - Many people drink more than the recommended level of alcohol, with some drinking
      substantially more. There is evidence that suggests that this leads to large
      health and social costs, and price is often proposed as a tool for reducing
      consumption. This paper uses quantile regression methods to estimate the
      differential price (and income) elasticities across the drinking distribution.
      This is also done for on-premise (pubs, bars and clubs) and off-premise
      (supermarkets and shops) alcohol separately. In addition, we examine the extent
      to which drinkers respond to price changes by varying the 'quality' of the
      alcohol that they consume. We find that heavy drinkers are much less responsive
      to price in terms of quantity, but that they are more likely to substitute with
      cheaper products when the price of alcohol increases. The implication is that
      price-based policies may have little effect in reducing consumption amongst the
      heaviest drinkers, provided they can switch to lower quality alternatives.

PMID- 30276495
TI  - Role of Percutaneous Chronic Total Occlusion Interventions in Patients with
      Ischemic Cardiomyopathy and Reduced Left Ventricular Ejection Fraction.
AB  - PURPOSE OF REVIEW: The purpose of this review is to examine current evidence on
      the benefit of chronic total occlusion (CTO) revascularization in patients with
      ischemic cardiomyopathy and propose a systematic approach on how and when to
      accomplish revascularization in these patients. RECENT FINDINGS: Coronary
      revascularization in patients with reduced ejection fraction (EF) is advocated
      for to improve left ventricular function and consequently clinical outcomes.
      Approximately 16-31% of angiograms in patients with advanced CAD are noted to
      have a concomitant coronary CTO. Its presence is a main predictor of worse
      outcomes. Over the past 15 years, advancements in interventional technologies and
      techniques have made it possible to treat CTO lesions percutaneously with success
      rates exceeding 90%. Different revascularization techniques have been organized
      into widely used algorithms for systematic CTO lesion crossing and treatment.
      Patients with reduced EF can be revascularized percutaneously with goal of
      complete functional revascularization. However, randomized prospective data is
      needed to justify the increased patient risks and healthcare costs associated
      with these procedures.

PMID- 30276498
TI  - Brain metabolism and related connectivity in patients with acrophobia treated by
      virtual reality therapy: an 18F-FDG PET pilot study sensitized by virtual
      exposure.
AB  - BACKGROUND: The aim of this pilot study is to investigate the impact of virtual
      reality exposure therapy (VRET) on brain metabolism and connectivity. Eighteen
      patients with acrophobia were assessed by an 18F-FDG PET scan sensitized by
      virtual exposure before treatment, and nine of them were assessed again after
      eight sessions of VRET. Statistical Parametric Mapping was used to study the
      correlations between metabolism and pretherapeutic clinical scores and to compare
      metabolism before and after VRET (p voxel < 0.005, corrected for cluster volume).
      Metabolic connectivity was evaluated through interregional correlation analysis.
      RESULTS: Before therapy, a positive correlation was found between scores on the
      behavioural avoidance test and left occipital metabolism (BA17-18). After VRET,
      patients presented increased metabolism in the left frontal superior gyri and the
      left precentral gyrus, which showed increased metabolic connectivity with
      bilateral occipital areas (BA17-18-19), concomitant with clinical recovery.
      CONCLUSIONS: This study highlights the exciting opportunity to use brain PET
      imaging to investigate metabolism during virtual exposure and reports the
      involvement of the visual-motor control system in the treatment of acrophobia by
      VRET.

PMID- 30276499
TI  - Microbial community dynamics in an ANAMMOX reactor for piggery wastewater
      treatment with startup, raising nitrogen load, and stable performance.
AB  - Bacterial community dynamics of the ANAMMOX reactor of an integrated "UASB +
      SHARON + ANAMMOX" system for treating piggery wastewater were investigated using
      the Illumina MiSeq method with samples obtained at ~ 2-week intervals during a
      314-day period. With aerobic activated sludge as seeds and low content artificial
      wastewater (NH4+-N 50 mg/L; NO2--N 55 mg/L) as influent for the ANAMMOX reactor,
      nitrogen removal was initially observed on day 38 with a removal rate 1.3 mg N L
      1 day-1, and increased to 90.4 mg N L-1 day-1 on day 55 with almost complete
      removal of ammonia and nitrite, indicating a successful startup of the reactor.
      Increasing influent load stepwise to NH4+-N 272.7 mg/L/NO2--N 300 mg/L, nitrogen
      removal rate increased gradually to 470 mg N L-1 day-1 on day 228, and maintained
      a stable level (~ 420 mg N L-1 day-1) following introduction of SHARON effluent
      since day 229. Correlation between microbial community dynamics and nitrogen
      removal capability was significant (r = 0.489, p < 0.001). Microbial community
      composition was determined by influent ammonia, influent nitrite, effluent
      nitrate and some undefined factors. Anammox bacteria, accounting for ~ 98.7% of
      Planctomycetes, became detectable (0.03% relative abundance) since day 38 and
      increased to 0.9% on day 58, well consistent with nitrogen removal performance of
      the reactor. Relative abundance of anammox bacteria gradually increased to 38.4%
      on day 140 with stepwise increased influent load; decreased to 0.4% on day 169
      because of nitrite inhibition; increased to 19.24% on day 233 when the influent
      load was dropped; kept at ~ 9.0% with SHARON effluent used as influent and
      dropped to 3.3% finally. Anammox bacteria, only Candidatus Brocadia and Ca.
      Kuenenia detected, were the most abundant at genus level. Ca. Brocadia related
      taxa were enriched firstly under low load and detectable during the entire
      experimental period. Three main groups represented by Ca. Brocadia related OTUs
      were enriched or eliminated at different loads, but Ca. Kuenenia related taxa
      were enriched only under high load (NO2--N > 300 mg/L), suggesting their
      different niches and application for different loads. These findings improve the
      understanding of relationships among microbial community/functional taxa, running
      parameters and reactor performance, and will be useful in optimizing running
      parameters for rapid startup and high, stable efficiency.

PMID- 30276500
TI  - Early onset of efficacy with erenumab in patients with episodic and chronic
      migraine.
AB  - BACKGROUND: Subcutaneous erenumab reduced monthly migraine days and increased the
      likelihood of achieving a >= 50% reduction at all monthly assessment points
      tested in 2 pivotal trials in episodic migraine (EM) and chronic migraine (CM).
      Early efficacy of migraine preventive medications is an important treatment
      characteristic to patients. Delays in achievement of efficacy can result in
      failed adherence. The objective of these post-hoc analyses were to evaluate
      efficacy in the first 4 weeks after initial subcutaneous administration of
      erenumab 70 mg, erenumab 140 mg, or placebo. METHODS: There is no generally
      accepted methodology to measure onset of action for migraine preventive
      medications. We used a comprehensive approach with data from both studies to
      evaluate change from baseline in weekly migraine days (WMD), achievement of >=
      50% reduction in WMD, and proportion of patients experiencing migraine measured
      on a daily basis. The 7-day moving averages were overlaid with observed data.
      RESULTS: In both studies (EM: N = 955; CM: N = 667), there was evidence of onset
      of efficacy of erenumab vs. placebo during the first week of treatment, which in
      some cases reached nominal significance. For EM the changes in WMD were (least
      squares mean [LSM] [95% CI]): placebo, - 0.1 (- 0.3, 0.0); erenumab 70 mg, - 0.3
      (- 0.5, - 0.2) p = 0.130; erenumab 140 mg, - 0.6 (- 0.7, - 0.4) p < 0.001. For CM
      the changes were: placebo, - 0.5 (- 0.8, - 0.3); erenumab 70 mg, - 0.9 (- 1.2, -
      0.7) p = 0.047; erenumab 140 mg, - 0.8 (- 1.1, - 0.5) p = 0.18. Achievement of >=
      50% reduction in WMD was observed as early as Week 1 (adjusted OR [95% CI]
      erenumab vs placebo) in EM: erenumab 70 mg, 1.3 (1.0, 1.9) p = 0.097; erenumab
      140 mg, 2.0 (1.4, 2.7) p < 0.001. A similar outcome was observed for CM: erenumab
      70 mg, 1.8 (1.1, 2.8) p = 0.011; erenumab 140 mg, 1.9 (1.2, 2.9) p = 0.009. Seven
      day moving averages of observed data showed each treatment arm differed from
      placebo by Week 1 (OR [95% CI]): in EM Day 3 for erenumab 140 mg, 0.7 (0.5, 1.0)
      p = 0.031 and at Day 7 for 70 mg, 0.6 (0.4, 0.8) p = 0.002; in CM: Day 6 for
      erenumab 70 mg, 0.6 (0.4, 0.9) p = 0.022 and at Day 7 for 140 mg, 0.7 (0.4, 1.0);
      p = 0.038. CONCLUSION: Erenumab showed early onset of efficacy with separation
      from placebo within the first week of treatment in both chronic and episodic
      migraine patients.

PMID- 30276501
TI  - Single center study of 53 consecutive patients with pituitary stalk lesions.
AB  - BACKGROUND: The etiological spectrum of pituitary stalk lesions (PSL) is wide and
      yet specific compared to the other diseases of the sellar and suprasellar region.
      Because of the pituitary stalk's (PS) critical location and role, biopsies of
      these lesions are rarely performed, and their underlying pathology is often a
      conundrum for clinicians. A pituitary MRI in association with a clinical context
      can facilitate their diagnosis. AIM: To present the various causes of PSL-their
      clinical, hormonal, histopathological, and MRI characteristics in order to gain
      better insight into this pathology. METHOD: A retrospective observational study
      consisting of 53 consecutive patients with PSL of the mean age 32 +/- 4.2 years
      (range 6-67), conducted at the Department for Neuroendocrinology, Clinical Center
      of Serbia 2010-2018. RESULTS: Congenital malformations were the most common cause
      of PSL in 25 of 53 patients (47.1%), followed by inflammatory (9/53; 16.9%) and
      neoplastic lesions (9/53; 16.9%). The exact cause of PSL was established in 31
      (58.4%) patients, of whom 23 were with congenital PS abnormalities and 8 with
      histopathology of PSL (7 neoplastic and 1 Langerhans Cell Hystiocytosis). A
      probable diagnosis of PSL was stated in 12 patients (22.6%): 6 with lymphocytic
      panhypophysitis, while Rathke cleft cyst, tuberculosis, dissemination of
      malignancy in PS were each diagnosed in 2 patients. In 10 patients (18.8%), the
      etiology of PSL remained unknown. CONCLUSION: Due to the inability of
      establishing an exact diagnosis, the management and prognosis of PSL are
      difficult in many patients. By presenting a wide array of causes implicated in
      this condition, we believe that our study can aid clinicians in the challenging
      cases of this pathology.

PMID- 30276502
TI  - Force matching as a stepping stone to QM/MM CB[8] host/guest binding free
      energies: a SAMPL6 cautionary tale.
AB  - Use of quantum mechanical/molecular mechanical (QM/MM) methods in binding free
      energy calculations, particularly in the SAMPL challenge, often fail to achieve
      improvement over standard additive (MM) force fields. Frequently, the
      implementation is through use of reference potentials, or the so-called "indirect
      approach", and inherently relies on sufficient overlap existing between MM and
      QM/MM configurational spaces. This overlap is generally poor, particularly for
      the use of free energy perturbation to perform the MM to QM/MM free energy
      correction at the end states of interest (e.g., bound and unbound states).
      However, by utilizing MM parameters that best reproduce forces obtained at the
      desired QM level of theory, it is possible to lessen the configurational
      disparity between MM and QM/MM. To this end, we sought to use force matching to
      generate MM parameters for the SAMPL6 CB[8] host-guest binding challenge,
      classically compute binding free energies, and apply energetic end state
      corrections to obtain QM/MM binding free energy differences. For the standard set
      of 11 molecules and the bonus set (including three additional challenge
      molecules), error statistics, such as the root mean square deviation (RMSE) were
      moderately poor (5.5 and 5.4 kcal/mol). Correlation statistics, however, were in
      the top two for both standard and bonus set submissions ([Formula: see text] of
      0.42 and 0.26, [Formula: see text] of 0.64 and 0.47 respectively). High RMSE and
      moderate correlation strongly indicated the presence of systematic error.
      Identifiable issues were ameliorated for two of the guest molecules, resulting in
      a reduction of error and pointing to strong prospects for the future use of this
      methodology.

PMID- 30276504
TI  - The Integrated Health Hub (IHH) Model: The Evolution of a Community Based Primary
      Care and Mental Health Centre.
AB  - There is increasing demand for comprehensive community healthcare that integrates
      community mental health and primary care services. The Canadian Mental Health
      Association-Durham Branch provides an example of how the Integrated Health Hub
      (IHH) Model evolved organically to meet this need. The Framework Method was used
      to analyze interviews and focus groups with 29 participants. Results reveal five
      key domains critical to the development of the IHH Model (1) Communication; (2)
      Hub 'Nuances'; (3) Leadership; (4) Staff; and (5) Challenges. These findings
      provide insights for other community mental health organizations wishing to
      provide comprehensive integrated community healthcare services.

PMID- 30276503
TI  - An explicit-solvent hybrid QM and MM approach for predicting pKa of small
      molecules in SAMPL6 challenge.
AB  - In this work we have developed a hybrid QM and MM approach to predict pKa of
      small drug-like molecules in explicit solvent. The gas phase free energy of
      deprotonation is calculated using the M06-2X density functional theory level with
      Pople basis sets. The solvation free energy difference of the acid and its
      conjugate base is calculated at MD level using thermodynamic integration. We
      applied this method to the 24 drug-like molecules in the SAMPL6 blind pKa
      prediction challenge. We achieved an overall RMSE of 2.4 pKa units in our
      prediction. Our results show that further optimization of the protocol needs to
      be done before this method can be used as an alternative approach to the well
      established approaches of a full quantum level or empirical pKa prediction
      methods.

PMID- 30276505
TI  - Determinants for quality of life trajectory patterns in patients with type 2
      diabetes.
AB  - PURPOSE: The purpose of the study was to identify quality of life (QoL)
      trajectory patterns and the determinants in patients with Type 2 diabetes (T2DM).
      METHODS: A longitudinal design was employed. Totally, 466 patients with T2DM
      recruited from five diabetic clinics in Taiwan were participants of this study.
      Demographic and disease characteristics, biomedical factors (HbA1c levels and
      body mass index), psychosocial factors (self-care behaviors, social support,
      resilience, diabetes distress), and QoL were collected at baseline. QoL was
      further measured every 6 months for four waves after baseline. Latent class
      growth analysis was used to identify QoL trajectory patterns. The multinomial
      logistic regression was further applied to explore the important determinants of
      different QoL trajectory patterns. RESULTS: The "steadily poor" (n = 27, 5.8%),
      "consistently moderate" (n = 174, 37.3%), and "consistently good" (n = 265,
      56.9%) trajectory patterns were identified. The HbA1c levels (OR 2.16) and
      diabetes distress (OR 1.18) were important for determining participants in the
      "steadily poor" QoL trajectory pattern. HbA1c levels (OR 1.25) and diabetes
      distress (OR 1.14) were important for determining participants in the
      "consistently moderate" QoL trajectory pattern. CONCLUSIONS: To prevent
      development of relatively worse QoL trajectory patterns in patients with T2DM in
      a timelier manner, healthcare providers could regularly assess the QoL and
      provide intervention, especially for those with high HbA1c levels and high
      diabetes distress. Meanwhile, early intervention for decreasing HbA1c levels and
      diabetes distress may improve the trajectory development of QoL in patients with
      T2DM.

PMID- 30276506
TI  - Psychometric properties of a modified version of the Weiss Functional Impairment
      Rating Scale-Parent Report (WFIRS-P) in a clinical sample of children with
      aggressive behavior.
AB  - PURPOSE: To evaluate the psychometric properties of a German modification of the
      Weiss Functional Impairment Rating Scale-Parent Report for children with
      aggressive and oppositional behavior problems (WFIRS-P for ODD/CD). METHODS: Data
      were collected from a clinical sample of children (6-12 years; 96% boys) with
      oppositional defiant disorder (ODD) and conduct disorder (CD) (N = 219). The
      WFIRS-P conceptual framework was evaluated using confirmatory factor analyses
      (CFA). Reliability was estimated using internal consistency (Cronbach's alpha)
      and omega statistics. Validity was assessed through correlations between WFIRS-P
      for ODD/CD domain scores and parent-rated scales on symptoms of ODD, CD,
      attention-deficit/hyperactivity disorder (ADHD), a broad range of other
      behavioral and emotional problems, and scales on health-related quality of life
      and family burden. RESULTS: CFA of the WFIRS-P for ODD/CD revealed that a
      bifactor model, with a general factor accounting for common variance (omegaH =
      0.23-0.48) and independent specific group factors accounting for additional
      variance in item scores (omegaS = 0.37-0.60), best fits the data. Thus, CFA
      confirmed the theoretical assumption of a general construct of impairment (total
      scale) and additional specific impairments (subscales, e.g., family, social
      activities). Cronbach's alpha coefficient exceeded 0.70 for all subscales. Omega
      statistics showed that both the general construct and specific factors accounted
      for item variance. As expected, correlations with symptoms scales for ODD/CD and
      ADHD were low to moderate. CONCLUSIONS: The use of the parent-rated WFIRS for
      ODD/CD in identifying ODD- and CD-related impairment in children is
      psychometrically supported. The scale can be employed to assess functional
      impairment in children with aggressive behavior problems.

PMID- 30276507
TI  - MiR-539 Targets MMP-9 to Regulate the Permeability of Blood-Brain Barrier in
      Ischemia/Reperfusion Injury of Brain.
AB  - Cerebral ischemia/reperfusion (I/R) injury severely threatens human life, while
      the potential mechanism underlying it is still need further exploration. The rat
      model of cerebral I/R injury was established using middle cerebral artery
      occlusion (MCAO). The rat microvascular endothelial cell line bEND.3 was exposed
      to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic ischemic condition in
      vitro. Evans blue was performed to determine the blood-brain barrier (BBB)
      permeability. Real-time PCR and western blot were performed to determine gene
      expression in mRNA and protein level, individually. Luciferase reporter assay was
      conducted to determine the relationship between miR-539 and MMP-9. The infarct
      volume and BBB permeability of cerebral (I/R) rats were significantly greater
      than Sham group. The expression of miR-539 was decreased, while MMP-9 was
      increased in the brain tissues of I/R injury rats and OGD/R pretreated bEND.3. Up
      regulated miR-539 in OGD/R pretreated bEND.3 significantly promoted the BBB
      permeability. MiR-539 targets MMP-9 to regulate its expression. OGD/R treatment
      significantly promoted the BBB permeability in bEND.3, miR-539 mimic transfection
      abolished the effects of OGD/R, while co-transfected with pcDNA-MMP-9 abolished
      the effects of miR-539 mimic. MiR-539 targets MMP-9 and further regulates the BBB
      permeability in cerebral I/R injury.

PMID- 30276508
TI  - Reaching Uninsured Overweight and Obese Children Through the FitKids Mobile
      Lifestyle Modification Program: Lessons Learned.
AB  - The US prevalence of childhood obesity remains high with ~ 1 in five children
      diagnosed with obesity, and rates of obesity are likely higher in uninsured and
      Medicaid populations than in those with private insurance. To understand the
      impact of an obesity intervention, an established mobile clinic program conducted
      a study to determine whether a FitKids Mobile Lifestyle Modification Program
      could reach overweight and obese uninsured children. Eighty-six children (ages 8
      18 years) participated in the FitKids study over two trial periods. The first
      trial consisted of four total visits, but subsequent visits after the initial
      visit had poor turnout. Through telephonic interviews, parents described positive
      aspects of the program: (1) providers' individual attention to their child, (2)
      increased knowledge about obesity, nutrition, and diet, (3) and parent and child
      were motivated to be more active. The most common barriers noted for return
      visits were (1) personal/family factors, (2) scheduling issues, and (3) distance
      to the clinic. As quality improvement, for the second trial, total number of
      visits was reduced from 4 to 3 visits and reminder calls were instituted.
      Percentage of children who returned for the third visit (67.5% for Trial 1 and
      62.5% for Trial 2) was not improved despite quality improvement interventions.
      Mobile clinics provide a unique solution to reach underserved overweight and
      obese children to help them create a more active and healthy lifestyle, but more
      research is needed to understand how best to optimize programs.

PMID- 30276509
TI  - NLRP3/Caspase-1 Pathway-Induced Pyroptosis Mediated Cognitive Deficits in a Mouse
      Model of Sepsis-Associated Encephalopathy.
AB  - Sepsis-associated encephalopathy (SAE) is a common complication that leads to
      long-term cognitive impairments and increased mortality in sepsis survivors. The
      mechanisms underlying this complication remain unclear and an effective
      intervention is lacking. Accumulating evidence suggests the nucleotide-binding
      domain-like receptor protein3 (NLRP3)/caspase-1 pathway is involved in several
      neurodegenerative diseases. Thus, we hypothesized that the NLRP3/caspase-1
      pathway is involved in NLRP3-mediated pyroptosis, maturation and release of
      inflammatory cytokines, and cognitive deficits in SAE. We used the NLRP3
      inhibitor MCC950 and the caspase-1 inhibitor Ac-YVAD-CMK to study the role of the
      NLRP3/caspase-1 pathway in pyroptosis and cognitive deficits in a mouse model of
      SAE. Mice were randomly assigned to one of six groups: sham+saline, sham+MCC950,
      sham+Ac-YVAD-CMK, cecal ligation and puncture (CLP)+saline, CLP+MCC950, and
      CLP+Ac-YVAD-CMK. Surviving mice underwent behavioral tests or had hippocampal
      tissues collected for histochemical analysis and biochemical assays. Our results
      show that CLP-induced hippocampus-dependent memory deficits are accompanied by
      increased NLRP3 and caspase-1 positive cells, and augmented protein levels of
      NLRP3, caspase-1, gasdermin-D, and pro-inflammatory cytokines in the hippocampus.
      In addition, administration of MCC950 or Ac-YVAD-CMK rescues cognitive deficits
      and ameliorates increased hippocampal NLRP3-mediated neuronal pyroptosis and pro
      inflammatory cytokines. Our results suggest that the NLRP3/caspase-1 pathway
      induced pyroptosis mediates cognitive deficits in a mouse model of SAE.

PMID- 30276510
TI  - Normative Pentacam anterior and posterior corneal elevation measurements: effects
      of age, sex, axial length and white-to-white.
AB  - PURPOSE: To provide normal corneal elevation data for a large Caucasian
      population and to determine the impacts on these data of age, sex, axial length
      (AXL) and horizontal white-to-white (WW). SETTING: Centro Internacional de
      Oftalmologia Avanzada, Madrid, Spain. DESIGN: Retrospective, cross-sectional,
      observational. METHODS: In this retrospective, cross-sectional, observational
      study, anterior and posterior corneal elevations were measured in 789 right eyes
      of subjects with no ocular disease at the thinnest corneal location in relation
      to a fixed 8-mm best-fit sphere using the Pentacam, and AXL and WW were measured
      with the IOLMaster. A multiple linear regression model was used to assess the
      effects of age, sex, AXL and WW on the elevation data. RESULTS: Mean subject age
      was 50.5 +/- 15 years (range 17-93 years); 64% were women. Mean anterior and
      posterior corneal elevations were 1.99 +/- 1.75 um (- 7 to 10 um) and 7.70 +/-
      5.7 um (- 6 to 28 um). Anterior corneal elevations were higher by 0.165 MUm and
      0.033 MUm for every mm reduction in AXL and every year reduction in age,
      respectively. Sex and WW were not significant predictors of anterior elevations
      (R2 = 7.7%). Posterior corneal elevation increased by 0.186 MUm/year of age,
      0.707 MUm/mm reduction in WW and 0.819 MUm/mm reduction in AXL. This variable was
      also 0.866 MUm greater in men (R2 = 34.4%). CONCLUSION: Anterior corneal
      elevations decrease with age and are higher for shorter AXL but are not
      influenced by sex or WW. Posterior corneal elevations increase with age,
      decreasing AXL, decreasing WW and are higher in men.

PMID- 30276511
TI  - An unusual synthesis of 3-(2-(arylamino)thiazol-4-yl)-2H-chromen-2-ones from
      ethyl 2-(chloromethyl)-2-hydroxy-2H-chromene-3-carboxylate via benzopyran ring
      opening.
AB  - An unusual and unexpected synthesis of 3-(2-(arylamino)thiazol-4-yl)-2H-chromen-2
      ones has been observed by the reaction of ethyl 2-(chloromethyl)-2-hydroxy-2H
      chromene-3-carboxylate with various arylthioureas in ethanol under mild reaction
      conditions with excellent yields. The ambiguity in the structure of the obtained
      products has been solved by recording its single-crystal X-ray analysis. This
      protocol has been found to be a novel approach for the preparation of title
      compounds via benzopyran ring opening. A systematic plausible mechanism has been
      proposed for the formation of the product. Also, an efficient one-pot three
      component method has been demonstrated for the formation of title compounds
      starting from salicylaldehyde.

PMID- 30276512
TI  - Risk assessment of vascular disorders by a supplementary hand-arm vascular
      weighting of hand-transmitted vibration.
AB  - PURPOSE: To provide an updated epidemiological validation for a supplementary
      method for assessing the risk of vascular disorders from hand-transmitted
      vibration. METHODS: The occurrence of vibration-induced white finger (VWF) in the
      vibration-exposed workers of the Italian cohort of the EU VIBRISKS study was
      related to measures of daily vibration exposure expressed in terms of r.m.s.
      acceleration magnitude normalised to an 8-h day, frequency weighted according to
      either the frequency weighting Wh defined in international standard ISO 5349
      1:2001 [Ah(8) in ms- 2] or the hand-arm vascular frequency weighting Wp proposed
      in the ISO technical report (TR) 18570:2017 [Ap(8) in ms- 2]. To estimate a
      threshold value for vascular hand-arm vibration risk, the Wp-weighted vibration
      exposure value Ep,d (in ms- 1.5) was calculated according to the ISO/TR document.
      The difference in the predictions of VWF between the exposure measures calculated
      with the frequency weightings Wh or Wp was investigated by means of logistic
      modelling. RESULTS: Measures of daily vibration exposure constructed with the
      frequency weighting Wp [Ap(8) and Ep,d], which gives more importance to
      intermediate- and high-frequency vibration, were better predictors of the
      occurrence of VWF in the vibration-exposed workers than the metric derived from
      the conventional ISO frequency weighting Wh [Ah(8)]. There was some
      epidemiological evidence for a threshold value of Ep,d for the onset of VWF in
      the vibration-exposed workers. CONCLUSIONS: Measures of daily vibration exposure
      evaluated with the vascular weighting Wp performed better for the predictions of
      VWF than those obtained with the frequency weighting Wh recommended in ISO 5349
      1.

PMID- 30276513
TI  - VOC sources and exposures in nail salons: a pilot study in Michigan, USA.
AB  - PURPOSE: Exposures of nail salon technicians have received attention due to the
      potentially toxic materials used in nail products, which include volatile organic
      compounds (VOCs) such as formaldehyde and methyl methacrylate (MMA). This study
      characterized area and personal concentrations and other indoor air parameters in
      17 nail salons in fall and winter seasons in three areas of Michigan. METHODS:
      VOC samples were analyzed using thermal desorption, gas chromatography and mass
      spectroscopy, and the VOC composition of 35 nail products (e.g., polish, top
      coat, base coat) was measured using headspace sampling. Ventilation rates were
      derived using CO2 concentrations, occupancy and building information, and VOC
      sources were apportioned by a novel application of chemical mass balance models.
      RESULTS: We detected ethyl acetate, propyl acetate, butyl acetate, MMA, n-heptane
      and toluene in most salons, and benzene, D-limonene, formaldehyde, and ethyl
      methacrylate in some salons. While MMA was not measured in the consumer and
      professional products, and the use of pure MMA in salons has been not been
      permitted since the 1970s, MMA was found in air at concentrations from 100 to
      36,000 ug/m3 in 15 of 17 salons; thus its use appears to be commonplace in the
      industry. Personal measurements, representing exposures to workers and clients,
      were about twice those of the area measurements for many VOCs. CONCLUSION: This
      study identifies the products responsible for emissions, shows the widespread
      presence of MMA, and documents low ventilation rates in some salons. It also
      demonstrates that "informal" short-term sampling approaches can evaluate chemical
      exposures in nail salons, providing measurements that can be used to protect a
      potentially susceptible and vulnerable population. Additional controls, including
      restrictions on the VOC compositions and improved ventilation, can reduce
      exposures to salon workers and clients.

PMID- 30276514
TI  - Postoperative morbidity of free flaps in head and neck cancer reconstruction: a
      report regarding 215 cases.
AB  - OBJECTIVES: The aim of this study was to identify the factors responsible for
      free flap failure, the surgical complications, and the non-oral feeding period in
      patients treated for an oral squamous cell carcinoma. MATERIALS AND METHODS: This
      multicentric study included 215 patients treated by tumour resection with
      immediate free flap reconstruction for an OSCC between 2010 and 2016. All of the
      patient medical files were reviewed and the data regarding the patient medical
      history, the tumour-related features, the surgical procedure, and the
      postoperative recovery were compiled. A statistical analysis with univariate and
      multivariate logistic regression was carried out. RESULTS: The free flap success
      rate was 94.4% in our series. A postoperative complication occurred in 101
      patients (41%). Minor surgical complications were shown to increase the free flap
      failure rate (OR 3.32; p = 0.04). A major surgical complication was encountered
      in 48 patients (22.3%), and these were linked to minor surgical complications (OR
      2.89; p = 0.004) and the use of a tracheostomy (OR 5.76, p = 0.002). Conversely,
      a medical history of high blood pressure had a protective effect (p = 0.04). The
      non-oral feeding rate at the end of the hospital stay was 28.4%, and it
      correlated with the tracheostomy (p = 0.002), as well as the major and the minor
      surgical complications (p = 0.04). CONCLUSION-CLINICAL RELEVANCE: Free flap
      reconstruction is a safe and reliable technique with head and neck cancer
      reconstruction. Postoperative care favouring early and safe oral-feeding, and
      avoiding a tracheostomy can reduce the incidence of surgical complications after
      OSCC reconstruction.

PMID- 30276515
TI  - Periodontal outcome and additional clinical quality criteria of lithium
      disilicate restorations (Empress 2) after 14 years.
AB  - OBJECTIVES: To evaluate the clinical quality of tooth-supported crowns (SCs),
      implant-supported crowns (ISCs), and fixed dental prosthesis (FDPs) made of a
      lithium-disilicate glass-ceramic framework material (IPS Empress 2, Ivoclar
      Vivadent) after long-term use. MATERIALS AND METHODS: Between 1997 and 1999, 184
      restorations (106 SCs, 32 ISCs, 33 FDPs, 13 diverse restorations) were placed in
      73 patients. In 2012/2013, all patients with functioning restorations were
      invited to participate in a clinical follow-up examination. To investigate the
      clinical quality, modified California Dental Association (CDA) criteria,
      periodontal health, and the patient's opinion were evaluated. RESULTS: After 14
      years on average, 50 restorations were available for evaluation of the CDA
      criteria and the patient's opinion, and 24 restorations were available for the
      periodontal health evaluation. Surface, color, anatomic shape, and margin
      integrity were considered to be in the range of excellence in 54, 78, 96, and
      88%, respectively. There were no unacceptable defects. Most patients (64%) were
      still entirely satisfied with their restorations. Mean probing depths were
      significantly higher on teeth with tooth-supported Empress 2 restorations than on
      control teeth (p = 0.0401). No significant relationship was found between surface
      quality and plaque accumulation (p = 0.9450, generalized linear mixed model) or
      between surface quality and periodontal probing >= 4 mm (p = 0.4184, generalized
      linear mixed model). CONCLUSIONS: The clinical quality of the Empress 2
      restorations that had survived 14 years on average was totally satisfactory with
      regard to esthetics, design, and patient's opinion. The periodontal health of all
      ceramic restored teeth requires further investigation. CLINICAL SIGNIFICANCE: The
      practitioner's choice of dental materials is based, at best, on long-term
      experience. With diminishing concerns about the clinical longevity of all-ceramic
      restorations, the grading of clinical quality based on esthetics, design,
      periodontal response, and patients' opinions could, nowadays, serve as a measure
      for the efficiency of dental ceramic.

PMID- 30276516
TI  - Microbial diversity in infections of patients with medication-related
      osteonecrosis of the jaw.
AB  - OBJECTIVES: A central role of infections in the treatment of MRONJ patients is
      widely accepted. An investigation of the MRONJ lesions' biofilms as potential
      pathogens seems logical. MATERIALS AND METHODS: We investigated the clinical data
      of our MRONJ patients who received surgery in advanced stage of the disease.
      Special attention was granted to the local colonizers harvested from osseous
      MRONJ specimens and submucosal putrid infections. RESULTS: Eleven out of 71
      patients presented a spontaneous onset of the disease and for 60 out of 71
      patients a trigger was detected. Breast cancer (29.6%) and prostate cancer
      (22.5%) were the most frequent underlying disease for prescription of an
      antiresorptive therapy, mostly zoledronate. Submucosal soft tissue biofilms
      significantly differed from biofilms harvested from the MRONJ lesions bottom, yet
      the most frequent bacteria were equally present in both groups: Streptococcus
      species (spp.), Prevotella spp., Actinomyces spp., Veillonella spp., and
      Parvimonas micra. The cephalosporins, cefuroxime and cefotaxime, and beta-lactam
      antibiotics with beta-lactamase inhibitor revealed the greatest susceptibility
      for the detected bacteria. CONCLUSION: The bacteria from the submucosal areas and
      the bottom of the infected bone presented comparable susceptibility to the common
      antibiotics regimes. Streptococcus spp., Prevotella spp., and Veillonella spp.
      present a high abundance in MRONJ lesions beside Actinomyces spp. The MRONJ
      lesions bottom is in many cases not infected by Actinomyces spp. CLINICAL
      RELEVANCE: The removal of the necrotic bone reduces the variety of bacteria found
      in MRONJ lesions, in particular at the bottom of the lesion.

PMID- 30276517
TI  - Oral symptoms and oral health-related quality of life in patients with chronic
      kidney disease from predialysis to posttransplantation.
AB  - OBJECTIVE: This prospective follow-up cohort study analyzed chronic kidney
      disease (CKD) patients' oral symptoms, health habits, and oral health-related
      quality of life (OHRQoL), from predialysis to posttransplantation. A simplified
      questionnaire method (Oral Health Quality Score, OHQS), based on these and
      clinical findings, was constructed and tested for identifying patients in need
      for referral to a dentist. MATERIAL AND METHODS: Fifty-three CKD patients were
      followed up for a mean of 10.3 years. Clinical oral, radiological, and salivary
      examination was performed at baseline and posttransplantation. Total Dental Index
      (TDI) indicating inflammation was calculated. The patients filled out a
      questionnaire on symptoms, oral hygiene and health care habits, smoking, alcohol
      use, and medication. General health-related quality of life was assessed with the
      15-dimensional (15D) instrument at posttransplantation. Descriptive and
      analytical methods were used in statistics. RESULTS: OHQS significantly
      correlated with high TDI (p = 0.017), number of teeth (p = 0.031), and
      unstimulated salivary flow rate (p = 0.001) in transplanted patients. Number of
      daily medications showed a negative correlation with the OHQS (r = - 0.30; p =
      0.028). The prevalence of oral symptoms was slightly, but not significantly, more
      common posttransplantation compared with predialysis stage. CONCLUSION: OHQS
      identified patients with high oral inflammatory score thus confirming our study
      hypothesis. CLINICAL RELEVANCE: Use of OHQS and measuring salivary flow indicate
      patients at risk for oral diseases. These markers might be easy to use chair-side
      also by auxiliary personnel.

PMID- 30276518
TI  - Gerald M. Edelman (1929-2014).

PMID- 30276519
TI  - Effect of mechanical thrombectomy alone or in combination with intravenous
      thrombolysis for acute ischemic stroke.
AB  - OBJECTIVE AND DESIGN: Whether combining intravenous thrombolysis (IVT) and
      mechanical thrombectomy (MT) is superior to mechanical thrombectomy alone for
      large vessel occlusion acute ischemic stroke is still uncertain. Our aim was to
      compare the safety and the efficacy of these two therapeutic strategies.
      MATERIALS: Patients with acute ischemic stroke secondary to anterior circulation
      large vessel occlusion. METHODS: A retrospective analysis was conducted. IVT was
      performed with full dose recombinant tissue plasminogen activator. MT alone was
      performed only if intravenous thrombolysis was contraindicated. Primary outcomes
      were successful reperfusion, 3-month functional independence, symptomatic
      intracranial hemorrhage (sICH), and 3-month mortality. RESULTS: 325 patients were
      analyzed: 193 treated with combined IVT and MT, 132 with MT alone. The combined
      treatment group showed higher systolic blood pressure (140 [80-230] vs 150 [90
      220]; p = 0.036), rate of good collaterals (55.9% vs 67%; p = 0.03), use of
      aspiration devices (68.2% vs 79.3%; p = 0.003) and shorter onset-to-reperfusion
      time (300 [90-845] vs 288 [141-435]; p = 0.008). No differences were found in the
      efficacy and safety outcomes except for mortality which was lower in the combined
      treatment group (36.4% vs 25.4%; p = 0.02). However, after multivariable analysis
      combined treatment was not associated with lower mortality (OR 1.47; 95% CI 0.73
      2.96; p = 0.3). CONCLUSIONS: Our study suggests that mechanical thrombectomy
      alone is effective and safe in patients with contraindications to intravenous
      thrombolysis. Preceding use of IVT in eligible patients was not associated with
      increased harm or benefit. Randomized controlled trials are needed to clarify
      whether intravenous thrombolysis before mechanical thrombectomy is associated
      with additional benefit.

PMID- 30276521
TI  - Collaboration of Cerebello-Rubral and Cerebello-Striatal Loops in a Motor
      Preparation Task.
AB  - In this study, we used fMRI to identify brain regions associated with
      concentration (sustained attention) during a motor preparation task. In
      comparison with a non-concentration task, increased activities were observed (P <
      0.05, FWE-corrected P values) in cerebellar lobules VI and VII, motor cortex, pre
      supplementary motor area (pre-SMA), thalamus, red nucleus (RN), and caudate
      nucleus (CN). Moreover, analysis of effective connectivity inter-areal
      (psychophysiological interactions) showed that during preparation, concentration
      related brain activity increase was dependent on Cerebello-thalamo-pre-SMA-RN and
      Pre-SMA-CN-thalamo-M1 loops. We postulate that, while pre-SMA common to both
      loops is specifically involved in the movement preparation and readiness for
      voluntary movement through the striatum, the cerebellar lobule VI in conjunction
      with RN, likely through a cerebellar-rubro-olivary-cerebellar loop, might be
      implicated in concentration-related optimization of upcoming motor performances.

PMID- 30276520
TI  - Relation between functional connectivity and disability in multiple sclerosis: a
      non-linear model.
AB  - OBJECTIVE: To characterize the relation between brain functional connectivity and
      disability in patients with multiple sclerosis; to investigate the existence of
      critical values of both disability and functional connectivity corresponding to
      exhaustion of functional adaptive mechanisms. METHODS: Hundred-and-nineteen
      patients with no-to-severe disability and 42 healthy subjects were studied via 3T
      resting state functional MRI. Out of 116 regions extracted from Automated
      Anatomical Labeling atlas, pairs of regions whose functional connectivity
      correlated with Expanded Disability Status Score were identified. In patients,
      mathematical modeling was applied to find the best models describing Expanded
      Disability-Status-Score vs structural or functional measures. Functional vs
      structural models intersecting points were identified. RESULTS: Disability had
      direct linear relation with lesion load (r = 0.40, p < 5E-6), inverse of thalamic
      volume (r = 0.31 p < 1E-3) and functional connectivity in bi-frontal pairs of
      regions (r > 0.40, p < 0.04), while being non-linearly associated with functional
      connectivity in cerebello-temporal and cerebello-frontal pairs of regions (F >
      1.73, p < 0.02). Structural vs functional models intersecting points corresponded
      to Expanded Disability Status Score of 3.0. 85% of patients scoring more than 3.0
      showed functional connectivity in cerebello-temporal and cerebello-frontal pairs
      of regions below confidence intervals (z = [2.28-2.88] 95% CI) measured in
      healthy subjects. CONCLUSIONS: Functional brain connectivity changes may
      represent mechanisms of adaptation to structural damage and inflammation and may
      be not always clinically beneficial. Functional connectivity decreases in
      comparison with structural measure at Expanded Disability Status Score greater
      than 3.0, which may be critical and indicate exhaustion of compensatory
      mechanisms.

PMID- 30276523
TI  - Correction to: Situating Culturally Embodied Play Ecologies of Preschool
      Children: Lost in Transition.
AB  - The original version of this article unfortunately contained a mistake. The name
      of "Kristine Jensen de Lopez" was incorrectly tagged.

PMID- 30276524
TI  - Non-immune-related hypothyroidism and its relationship with excess iodine.
AB  - PURPOSE: In iodine-sufficient areas, autoimmune hypothyroidism has been regarded
      as the major subtype of hypothyroidism. Non-immune-related hypothyroidism has
      received little attention because it is considered to be rare. The aim of this
      study was to evaluate the prevalence of non-immune-related hypothyroidism in
      Korea and to identify its associating factors. METHODS: A total of 6434
      participants in the Korea National Health and Nutrition Examination Survey VI
      (2013-2015) without known thyroid disease who were examined for thyroid
      stimulating hormone, free thyroxine, TPO Ab, and urine iodine concentration (UIC)
      were enrolled. The weighted proportions, demographic variables, and severity of
      immune-related and non-immune-related hypothyroidism were compared. To assess the
      effect of iodine on hypothyroidism in TPO Ab positive or negative populations,
      the weighted prevalence of hypothyroidism was assessed in each population
      according to UIC or estimated iodine intake subgroups. RESULTS: The prevalence of
      undetected hypothyroidism in Korea was 3.8% (n = 233). Of these 233 cases, 171
      (71.8%) were non-immune-related. In the TPO Ab negative population, the
      prevalence of hypothyroidism was increased significantly in the subgroup with UIC
      between 250 and 749 ug/L (HR 2.12 [1.17, 3.83]) and >= 750 ug/L (HR 3.42 [1.93,
      6.04]) or the subgroups with estimated iodine intake >= 750 ug/day (HR 2.81
      [1.64, 4.80]). CONCLUSIONS: This nationwide study demonstrated that most cases of
      hypothyroidism in iodine-sufficient areas are non-immune-related and are
      associated with excess iodine above a certain level. More attention to this
      unrecognized but widespread potential health risk is needed.

PMID- 30276522
TI  - Cerebellar Cortex as a Therapeutic Target for Neurostimulation.
AB  - Non-invasive stimulation of the cerebellum is growingly applied both in the
      clinic and in research settings to modulate the activities of cerebello-cerebral
      loops. The anatomical location of the cerebellum, the high responsiveness of the
      cerebellar cortex to magnetic/electrical stimuli, and the implication of the
      cerebellum in numerous cerebello-cerebral networks make the cerebellum an ideal
      target for investigations and therapeutic purposes. In this mini-review, we
      discuss the potentials of cerebellar neuromodulation in major brain disorders in
      order to encourage large-scale sham-controlled research and explore this
      therapeutic aid further.

PMID- 30276526
TI  - Towards evidence-based management of patients treated with cardiotoxic
      chemotherapy: A collaborative effort of cardiologists and oncologists.

PMID- 30276525
TI  - Longitudinal echocardiographic and clinical follow-up of patients undergoing
      mitral valve surgery without concomitant tricuspid valve repair.
AB  - BACKGROUND: In patients with mild to moderate functional tricuspid regurgitation
      (TR) and absence of right ventricular dysfunction or tricuspid annulus (TA)
      dilatation, there is currently no indication for concomitant tricuspid valve (TV)
      repair during elective mitral valve (MV) surgery. However, long-term results are
      conflicting. Here, we sought to determine the clinical outcome of this cohort,
      the rate of TR progression after MV surgery and the role of MV aetiology.
      METHODS: Patients for elective MV surgery without concomitant TV repair were
      retrospectively analysed with longitudinal echocardiographic and clinical follow
      up, focusing on TR progression and MV aetiology. Linear regression analysis was
      performed for change in TR at follow-up, using pre-determined variables and
      confounders. RESULTS: In total 204 patients without TV repair were analysed.
      Development of more than moderate TR after a median of 3.1 [1.6-4.6] years was
      rarely seen: only in 2 out of 161 patients (1.2%) with known TR grade at follow
      up. Overall, median preoperative and late postoperative TR grade were equal (p =
      0.116). Subanalysis showed no significant difference in MV aetiology subgroups.
      Preoperative TR grade and male gender were inversely correlated to change in TR.
      Mortality was not influenced by the 1-year postoperative TR severity. CONCLUSION:
      Our data showed that in a study population of patients with mild to moderate TR
      undergoing MV surgery without concomitant TV repair, significant late TR was
      rarely seen. Based on our study, it is safe to waive concomitant TV repair in
      this specific patient cohort.

PMID- 30276527
TI  - Intermedin in Paraventricular Nucleus Attenuates Sympathoexcitation and Decreases
      TLR4-Mediated Sympathetic Activation via Adrenomedullin Receptors in Rats with
      Obesity-Related Hypertension.
AB  - Intermedin/adrenomedullin-2 (IMD/AM2), a member of the calcitonin gene-related
      peptide/AM family, plays an important role in protecting the cardiovascular
      system. However, its role in the enhanced sympathoexcitation in obesity-related
      hypertension is unknown. In this study, we investigated the effects of IMD in the
      paraventricular nucleus (PVN) of the hypothalamus on sympathetic nerve activity
      (SNA), and lipopolysaccharide (LPS)-induced sympathetic activation in obesity
      related hypertensive (OH) rats induced by a high-fat diet for 12 weeks. Acute
      experiments were performed under anesthesia. The dynamic alterations of
      sympathetic outflow were evaluated as changes in renal SNA and mean arterial
      pressure (MAP) in response to specific drugs. Male rats were fed a control diet
      (12% kcal as fat) or a high-fat diet (42% kcal as fat) for 12 weeks to induce OH.
      The results showed that IMD protein in the PVN was downregulated, but Toll-like
      receptor 4 (TLR4) and plasma norepinephrine (NE, indicating sympathetic
      hyperactivity) levels, and systolic blood pressure were increased in OH rats. LPS
      (0.5 ug/50 nL)-induced enhancement of renal SNA and MAP was greater in OH rats
      than in obese or control rats. Bilateral PVN microinjection of IMD (50 pmol)
      caused greater decreases in renal SNA and MAP in OH rats than in control rats,
      and inhibited LPS-induced sympathetic activation, and these were effectively
      prevented in OH rats by pretreatment with the AM receptor antagonist AM22-52. The
      mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK)
      inhibitor U0126 in the PVN partially reversed the LPS-induced enhancement of SNA.
      However, IMD in the PVN decreased the LPS-induced ERK activation, which was also
      effectively prevented by AM22-52. Chronic IMD administration resulted in
      significant reductions in the plasma NE level and blood pressure in OH rats.
      Moreover, IMD lowered the TLR4 protein expression and ERK activation in the PVN,
      and decreased the LPS-induced sympathetic overactivity. These results indicate
      that IMD in the PVN attenuates SNA and hypertension, and decreases the ERK
      activation implicated in the LPS-induced enhancement of SNA in OH rats, and this
      is mediated by AM receptors.

PMID- 30276529
TI  - Investigation of Vipera Anatolica Venom Disintegrin via Intracellular Uptake with
      Radiolabeling Study and Cell-Based Electrochemical Biosensing Assay.
AB  - Snake venoms are a natural biological source that has potential therapeutic value
      with various protein compounds. Disintegrins originally were discovered as a
      family of proteins from snake venoms composed of cysteine rich low molecular
      weight polypeptides. Disintegrins exhibit specific binding and higher affinity
      toward integrin with potential inhibition of function. Trans-membrane receptors
      of the integrin family may involve in many pathological conditions such as
      inflammation and tumor progression with important processes related to invasion
      and migration. Since disintegrins have the ability to bind to integrins, they
      could be used for cancer detection and treatment, and in monitoring of therapy in
      select cancer types. The main purpose of the study is to investigate disintegrin
      containing Vipera anatolica (VAT) crude venom potential for radiolabeling and
      intracellular uptake as well as electrochemical biosensing assay against U87MG
      human brain glioblastoma cells. For this purpose, VAT crude venom containing
      U87MG cell-specific disintegrin was investigated in terms of radiolabeling and
      intracellular uptake as well as electrochemical biosensing assay in comparison
      with echistatin (ECT) disintegrin in cells. The interaction between VAT crude
      venom and ECT with HEK293 human non-tumorigenic embryonic kidney cells and
      glioblastoma U87MG cells was electrochemically investigated using pencil graphite
      electrodes (PGEs). The interaction of the VAT crude venom and ECT with HEK293 and
      U87MG cells was detected according to the changes in oxidation signals. Then, VAT
      crude venom and echistatin were labeled with 131I via iodogen method.
      Intracellular uptakes of radiolabeled molecules were investigated in U87MG cell
      line. 131I-VAT can be an agent for imaging of glioblastoma cancer. Further work
      will focus on the production of large quantities of pure VAT disintegrin with a
      biotechnological approach to improving imaging agent.

PMID- 30276528
TI  - Chitosan/hyaluronic acid/plasmid-DNA nanoparticles encoding interleukin-1
      receptor antagonist attenuate inflammation in synoviocytes induced by interleukin
      1 beta.
AB  - Synovial inflammation mainly resulting from interleukin-1 beta (IL-1beta) plays a
      crucial role in the early and late stage of osteoarthritis. Recent progress in
      therapeutic gene delivery systems has led to promising strategies for local
      sustained target gene expression. The aim of this study was to design a
      nanoparticle made of chitosan (CS)/hyaluronic acid (HA)/plasmid-DNA (pDNA)
      encoding IL-1 receptor antagonist gene (pIL-1Ra) and furtherly use it to
      transfect the primary synoviocytes, and then investigate whether CS/HA/pIL-1Ra
      nanoparticles could make the synoviocytes overexpress functional IL-1Ra to
      attenuate inflammation induced by IL-1beta. In this study, CS was modified with
      HA to generate CS/HA nanoparticles and then combined with pIL-1Ra to form
      CS/HA/pIL-1Ra nanoparticles. The physicochemical characteristics results showed
      that CS/HA nanoparticles exhibited an appropriate particle size (144.9 +/- 2.8
      nm) and positive zeta potential ( + 28 mV). The gel retardation assay revealed
      that pDNA was effectively protected and released in a sustained manner more than
      15 days. Cytotoxicity results showed that CS/HA/pIL-1Ra nanoparticles had a safe
      range (0-80 MUg/ml) for the application to synoviocytes. RT-qPCR and western blot
      analysis demonstrated that CS/HA/pIL-1Ra nanoparticles were able to increase IL
      1Ra expression in primary synoviocytes, and reduce the mRNA and protein levels of
      matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13),
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in IL-1beta
      induced synoviocytes. Our findings indicated that CS/HA/pIL-1Ra nanoparticles
      efficiently transfected synoviocytes and attenuated synovitis induced by IL
      1beta, which will provide a potential strategy for OA synovitis.

PMID- 30276530
TI  - Novel three-dimensional image system for endoscopic ear surgery.
AB  - OBJECTIVE: The objective of this study was to evaluate the clinical outcomes of
      conventional two-dimensional (2D) endoscope with a novel computer-based three
      dimensional (3D) imaging system for otologic surgical procedures. METHODS: A
      conventional 2D monocular endoscope with a novel computer-based 3D imaging system
      was applied to 18 otologic surgical procedures, including chronic otitis media
      (COM), cholesteatoma, otosclerosis, external canal osteoma and cochlear implant.
      Operation duration and complications of COM and attic cholesteatoma were recorded
      to compare 2D and 3D endoscopic ear surgery. Questionnaires were completed by 35
      observers participating in the procedures and were used to evaluate clinical and
      potential side effects. RESULTS: The surgical procedures were performed smoothly
      for all patients. No patient required switching to conventional 2D endoscopic
      surgery. No significant differences were apparent in operation duration using the
      3D imaging system for chronic otitis media and attic cholesteatoma compared with
      conventional 2D endoscopic ear surgery. Thirty-five observers completed the
      questionnaires. Most of them agreed that this 3D imaging system enabled them to
      perceive stereoscopic vision (94%), provide superior depth perception (85%).
      Furthermore, 97.1% reported no visual fatigue or discomfort when observing the 3D
      images. CONCLUSION: Our study demonstrated that the computer-based 3D imaging
      system enables the application of 3D vision technology to otologic surgery. The
      system has no obvious side effects, such as visual fatigue or time delay. It not
      only facilitates performing the related surgical procedures but also helps in
      teaching and learning endoscopic ear surgeries.

PMID- 30276531
TI  - Frozen shoulder or shoulder stiffness from Parkinson disease?
AB  - PURPOSE: To understand the role of camptocormia (increased kyphosis) and postural
      alteration in Parkinson's disease in the development of shoulder pathology, with
      a special concern for adhesive capsulitis and shoulder stiffness. METHODS: A
      preliminary online search was carried out, with combination of keywords including
      "Parkinson," "Shoulder stiffness," "Frozen shoulder," "Adhesive capsulitis,"
      "Postural alteration," "Camptocormia". The retrieved papers were screened by
      title and abstract and those considered relevant to the aim of the review were
      read in full text and included. Relevant information were extracted and reported
      into text. RESULTS: Due to a severe impairment of posture, patients affected by
      PD show an increased thoracic kyphosis (camptocormia) and decreased mobility of
      the trunk that can yield a humeroacromial impingement syndrome and capsulitis,
      resulting in inflammation of the bursa, shoulder pain and reduction of movement.
      Furthermore, kinematic of the shoulder is allowed by the combined movement of the
      humerus, the scapula, the clavicle, the thoracic wall and thoracic spine. The
      thoracic spine and wall mobility are severely impaired in the parkinsonian
      patient, thus limiting the shoulder motion. CONCLUSION: The postural alteration
      observed in PD is the primum movens for shoulder pathology, since anterior tilt
      of the scapula, which occurs with the increment of thoracic kyphosis, yields to a
      subacromial impingement. A closed loop is then created, as the rigidity of the
      shoulder causes further alteration in the posture, which worsens the impingement
      syndrome and so on.

PMID- 30276532
TI  - Skin microvascular dysfunction as an early cardiovascular marker in primary
      hyperoxaluria type I.
AB  - BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an orphan inborn error of
      oxalate metabolism leading to hyperoxaluria, progressive renal failure, oxalate
      deposition, and increased cardiovascular complications. As endothelial
      dysfunction and arterial stiffness are early markers of cardiovascular risk, we
      investigated early endothelial and vascular dysfunction in young PH1 patients
      either under conservative treatment (PH1-Cons) or after combined kidney liver
      transplantation (PH1-T) in comparison to healthy controls (Cont-H) and patients
      with a past of renal transplantation (Cont-T). METHODS: Skin microvascular
      function was non-invasively assessed by laser Doppler flowmetry before and after
      stimulation by current, thermal, or pharmacological (nitroprussiate (SNP) or
      acetylcholine (Ach)) stimuli in young PH1 patients and controls. RESULTS: Seven
      PH1-Cons (6 F, median age 18.2) and 6 PH1-T (2 F, median age 13.3) were compared
      to 96 Cont-H (51 F, median age 14.2) and 6 Cont-T (4 F, median age 14.5). The
      endothelium-independent vasodilatation (SNP) was severely decreased in PH1-T
      compared to Cont-H. Ach, current-induced vasodilatation (CIV), and thermal
      response was increased in PH1-Cons and Cont-T compared to controls. CONCLUSIONS:
      PH1-T patients displayed severely decreased smooth muscle capacity to vasodilate.
      An exacerbated endothelial-dependent vasodilation suggests a role for silent
      inflammation in the early dysfunction of microcirculation observed in PH1-Cons
      and Cont-T.

PMID- 30276533
TI  - Hypertensive crisis in children and adolescents.
AB  - Hypertensive crisis is a relatively rare condition in children. However, if not
      treated, it might be life-threatening and lead to irreversible damage of vital
      organs. Clinical presentation of patients with hypertensive crisis can vary from
      very mild (hypertensive urgency) to severe symptoms (hypertensive emergency)
      despite similarly high blood pressure (BP). Individualized assessment of patients
      presenting with high BP with emphasis on the evaluation of end-organ damage
      rather than on the specific BP number is a key in guiding physician's initial
      management of a hypertensive crisis. The main aim of the treatment of
      hypertensive crisis is the prevention or treatment of life-threatening
      complications of hypertension-induced organ dysfunction, including neurologic,
      ophthalmologic, renal, and cardiac complications. While the treatment strategy
      must be directed toward the immediate reduction of BP to reduce the hypertensive
      damage to these organs, it should not be at a too fast rate to cause
      hypoperfusion of vital organs by an excessively rapid reduction of BP. Thus,
      intravenous continuous infusions rather than intravenous boluses of
      antihypertensive medications should be the preferable mode of initial treatment
      of children with hypertensive emergency.

PMID- 30276534
TI  - Towards adulthood with a solitary kidney.
AB  - Around 1/1000 people have a solitary kidney. Congenital conditions mainly include
      multicystic dysplastic kidney and unilateral renal aplasia/agenesis; acquired
      conditions are secondary to nephrectomy performed because of urologic structural
      abnormalities, severe parenchymal infection, renal trauma, and renal or pararenal
      tumors. Children born with congenital solitary kidney have a better long-term
      glomerular filtration rate than those with solitary kidney secondary to
      nephrectomy later in life. Acute and chronic adaptation processes lead to
      hyperfiltration followed by fibrosis in the remnant kidney, with further risk of
      albuminuria, arterial hypertension, and impaired renal function. Protective
      measures rely on non-pharmacological renoprotection (controlled protein and
      sodium intake, avoidance/limitation of nephrotoxic agents, keeping normal body
      mass index, and limitation of tobacco exposure). Lifelong monitoring should
      include blood pressure and albuminuria assessment, completed by glomerular
      filtration rate (GFR) estimation in case of abnormal values. In the absence of
      additional risk factors to solitary kidney, such assessment can be proposed every
      5 years. There is no current consensus for indication and timing of
      pharmacological intervention.

PMID- 30276535
TI  - Even gold standard methods of body water measurement are not always in perfect
      agreement.

PMID- 30276536
TI  - Comparison of echocardiographic changes in children with primary hypertension and
      hypertension due to mild to moderate chronic kidney disease.
AB  - BACKGROUND: Chronic systemic hypertension has a well-known association with
      increased cardiovascular morbidity and mortality. One of the most important
      target organs affected in systemic hypertension is the heart. In addition,
      chronic kidney disease (CKD) further increases the mortality from cardiovascular
      disease. The aim of this study was to evaluate the differences in the
      cardiovascular changes in pediatric patients with primary hypertension (pHTN) vs.
      those with secondary hypertension from chronic kidney disease (CKD-HTN). METHODS:
      This was a retrospective chart review of patients with CKD-HTN and pHTN. The
      medical records were reviewed for anthropometric data, biochemical assessment of
      renal function, and for cardiovascular changes on echocardiogram. RESULTS: Twenty
      three patients with pHTN and 29 patients with CKD-HTN were included in the study.
      There were no differences in age, gender, weight, height, body mass index, and
      blood pressure between the 2 groups. There was a high prevalence of left
      ventricular diastolic dysfunction among both the groups (CKD-HTN 25 vs. pHTN
      26%). Reduced mitral valve inflow Doppler E/A ratio, a marker of left ventricular
      diastolic dysfunction in echocardiogram, was more pronounced in CKD-HTN patents,
      in comparison to those with pHTN (p = 0.042). Also, diastolic function worsened
      with declining glomerular filtration rate in patients with CKD-HTN. Similarly,
      patients with CKD-HTN had a larger aortic root dimension when compared to
      patients with pHTN (p = 0.049). CONCLUSIONS: The prevalence of left ventricular
      diastolic dysfunction is similar in patients with pHTN and CKD-HTN. Patients with
      CKD-HTN appear to have more severe diastolic dysfunction and larger aortic root
      dimensions.

PMID- 30276539
TI  - Land subsidence phenomena investigated by spatiotemporal analysis of groundwater
      resources, remote sensing techniques, and random forest method: the case of
      Western Thessaly, Greece.
AB  - The main objective of the present study was to investigate land subsidence
      phenomena and the spatiotemporal pattern of groundwater resources in an area
      located in western Thessaly, Greece, by using remote sensing techniques and data
      mining methods. Specifically, the nonparametric Mann-Kendall test and the Sen's
      slope estimator were used to estimate the trend concerning the groundwater table,
      whereas a set of Synthetic Aperture Radar images, processed with the Persistent
      Scatterer Interferometry technique, were used investigate the spatial and
      temporal patterns of ground deformation. Random forest (RF) method was utilized
      to predict the subsidence deformation rate based on three related variables,
      namely: thickness of loose deposits, the Sen's slope value of groundwater-level
      trend, and the Compression Index of the formation covering the area of interest.
      The outcomes of the study suggest a strong correlation among the thickness of the
      loose deposits and the deformation rate and also show that a clear trend between
      the deformation rate and the fluctuation of the groundwater table exists. For the
      RF model and based on the validation dataset, the r square value was calculated
      to be 0.7503. In the present study, the potential deformation rate assuming
      different water pumping scenarios was also estimated. It was observed that with a
      mean decrease in the Sen's slope value of groundwater-level trend of 20%, there
      would be a mean decrease of 9.01% in the deformation rate, while with a mean
      increase in the Sen's slope value of groundwater-level trend of 20%, there would
      be a mean increase of 12.12% in the deformation rate. The ability of identifying
      surface deformations allows the local authorities and government agencies to take
      measures before the evolution of severe subsidence phenomena and to prepare for
      timely protection of the affected areas.

PMID- 30276537
TI  - Replication of a rare risk haplotype on 1p36.33 for autism spectrum disorder.
AB  - Hundreds of genes have been implicated in autism spectrum disorders (ASDs). In
      genetically heterogeneous conditions, large families with multiple affected
      individuals provide strong evidence implicating a rare variant, and replication
      of the same variant in multiple families is unusual. We previously published
      linkage analyses and follow-up exome sequencing in seven large families with
      ASDs, implicating 14 rare exome variants. These included rs200195897, which was
      transmitted to four affected individuals in one family. We attempted replication
      of those variants in the MSSNG database. MSSNG is a unique resource for
      replication of ASD risk loci, containing whole genome sequence (WGS) on thousands
      of individuals diagnosed with ASDs and family members. For each exome variant, we
      obtained all carriers and their relatives in MSSNG, using a TDT test to quantify
      evidence for transmission and association. We replicated the transmission of
      rs200195897 to four affected individuals in three additional families.
      rs200195897 was also present in three singleton affected individuals, and no
      unaffected individuals other than transmitting parents. We identified two
      additional rare variants (rs566472488 and rs185038034) transmitted with
      rs200195897 on 1p36.33. Sanger sequencing confirmed the presence of these
      variants in the original family segregating rs200195897. To our knowledge, this
      is the first example of a rare haplotype being transmitted with ASD in multiple
      families. The candidate risk variants include a missense mutation in SAMD11, an
      intronic variant in NOC2L, and a regulatory region variant close to both genes.
      NOC2L is a transcription repressor, and several genes involved in transcription
      regulation have been previously associated with ASDs.

PMID- 30276540
TI  - A review on anti-adhesion therapies of bacterial diseases.
AB  - BACKGROUND: Infections caused by bacteria are a foremost cause of morbidity and
      mortality in the world. The common strategy of treating bacterial infections is
      by local or systemic administration of antimicrobial agents. Currently, the
      increasing antibiotic resistance is a serious and global problem. Since the most
      important agent for infection is bacteria attaching to host cells, hence, new
      techniques and attractive approaches that interfere with the ability of the
      bacteria to adhere to tissues of the host or detach them from the tissues at the
      early stages of infection are good therapeutic strategies. METHODS: All available
      national and international databanks were searched using the search keywords.
      Here, we review various approaches to anti-adhesion therapy, including use of
      receptor and adhesion analogs, dietary constituents, sublethal concentrations of
      antibiotics, and adhesion-based vaccines. RESULTS: Altogether, the findings
      suggest that interference with bacterial adhesion serves as a new means to fight
      infectious diseases. CONCLUSION: Anti-adhesion-based therapies can be effective
      in prevention and treatment of bacterial infections, but further work is needed
      to elucidate underlying mechanisms.

PMID- 30276538
TI  - De novo unbalanced translocations have a complex history/aetiology.
AB  - We investigated 52 cases of de novo unbalanced translocations, consisting in a
      terminally deleted or inverted-duplicated deleted (inv-dup del) 46th chromosome
      to which the distal portion of another chromosome or its opposite end was
      transposed. Array CGH, whole-genome sequencing, qPCR, FISH, and trio genotyping
      were applied. A biparental origin of the deletion and duplication was detected in
      6 cases, whereas in 46, both imbalances have the same parental origin. Moreover,
      the duplicated region was of maternal origin in more than half of the cases, with
      25% of them showing two maternal and one paternal haplotype. In all these cases,
      maternal age was increased. These findings indicate that the primary driver for
      the occurrence of the de novo unbalanced translocations is a maternal meiotic non
      disjunction, followed by partial trisomy rescue of the supernumerary chromosome
      present in the trisomic zygote. In contrast, asymmetric breakage of a dicentric
      chromosome, originated either at the meiosis or postzygotically, in which the two
      resulting chromosomes, one being deleted and the other one inv-dup del, are
      repaired by telomere capture, appears at the basis of all inv-dup del
      translocations. Notably, this mechanism also fits with the origin of some simple
      translocations in which the duplicated region was of paternal origin. In all
      cases, the signature at the translocation junctions was that of non-homologous
      end joining (NHEJ) rather than non-allelic homologous recombination (NAHR). Our
      data imply that there is no risk of recurrence in the following pregnancies for
      any of the de novo unbalanced translocations we discuss here.

PMID- 30276541
TI  - Does routine repeat imaging change management in high-grade renal trauma? Results
      from three level 1 trauma centers.
AB  - PURPOSE: Guidelines call for routine reimaging of Grade 4-5 renal injuries at 48
      72 h. The aim of the current study is to evaluate the clinical utility of
      computed tomography (CT) reimaging in high-grade renal injuries. MATERIALS AND
      METHODS: We assembled data on 216 trauma patients with high-grade renal trauma at
      three level 1 trauma centers over a 19-year span between 1999 and 2017 in
      retrospectively collected trauma database. Demographic, radiographic, and
      clinical characteristics of patients were retrospectively reviewed. RESULTS: In
      total, 151 cases were Grade 4 renal injuries, and 65 were Grade 5 renal injuries.
      53.6% (81) Grade 4 and 15.4% (10) Grade 5 renal injuries were initially managed
      conservatively. Of the 6 asymptomatic cases where repeat imaging resulted in
      intervention, 100% had collecting system injuries at initial imaging. Collecting
      system injuries were only present in 42.9% of cases where routine repeat imaging
      did not trigger surgical intervention. Collecting system injury at the time of
      initial imaging was a statistically significant predictor of routine repeat
      imaging triggering surgical intervention (p = 0.022). Trauma grade and the
      presence of vascular injury were not significant predictors of intervention after
      repeat imaging in asymptomatic patients. CONCLUSION: In asymptomatic patients
      with high-grade renal trauma, the number needed to image is approximately one in
      eight (12.5%) to identify need for surgical intervention. There is potentially
      room to improve criteria for routine renal imaging in high-grade renal trauma
      based on the more predictive imaging finding of collecting system injury.

PMID- 30276542
TI  - A comprehensive analysis of cost of an active surveillance cohort compared to
      radical prostatectomy as primary treatment for prostate cancer.
AB  - INTRODUCTION: Active surveillance (AS) seems to be a cost-effective strategy.
      However, most publications are based on simulation models of theoretical cohorts,
      and long-term implications are not usually considered. OBJECTIVE: To assess the
      real cost differences of two cohorts of men with low-risk prostate cancer (PCa)
      treated with AS or laparoscopic radical prostatectomy (LRP) in a public health
      system. MATERIALS AND METHODS: Patients diagnosed from 2005 to 2009 were included
      in an AS program (Group 1) or treated with LRP at diagnosis (Group 2), with a
      minimum follow-up of 5 years. Actual costs for each patient were calculated on an
      individual basis: Group 1: semiannual PSA measurements and repeat biopsies are
      scheduled every 1-3 years. Costs of outpatient clinic visits were calculated, as
      well as all tests required for monitoring or active treatment. Group 2: costs of
      the procedure, emergency visits, re-admissions and outpatient clinic visits were
      calculated, as well as costs of oncological salvage therapies or functional
      surgical procedures. RESULTS: Out of 151 men diagnosed with low-risk PC, 54
      (35.8%) were included in an AS (Group 1) and 97 (64.2%) were submitted to LRP
      (Group 2). Mean follow-up for both groups was 6.5 years (SD 1.8) and 6.7 years
      (SD 1.4), respectively, p = 0.49. Group 1 had a total cost per patient of
      2970.47?. Group 2 had a total cost per patient of 5694.06?. CONCLUSIONS: AS was
      associated with cost-saving over LRP. This cost reduction of AS in the management
      of low-risk PCa is based on the accounting of real costs of individual patients
      and confirms previously published estimation-based reports.

PMID- 30276543
TI  - The effect of androgen deprivation treatment on subsequent risk of bladder cancer
      diagnosis in male patients treated for prostate cancer.
AB  - INTRODUCTION: Bladder cancer (BCa) is three-to-four times more common in men than
      in women. To explain this gender gap, several theories have been proposed,
      including the impact of androgen hormones. The aim of this study was to
      investigate the differential impact of androgen deprivation therapy (ADT) on
      subsequent risk of developing BCa in men with prostate cancer (PCa). METHODS: A
      total of 196,914 patients diagnosed with histologically confirmed localized PCa
      between 2000 and 2009 were identified in the SEER-Medicare insurance program
      linked database. Competing-risk regression analyses were performed to assess the
      risk of developing BCa adjusting for the risk of all-cause mortality. Univariable
      and multivariable competing-risk regression analyses were performed to test the
      effect of ADT on BCa incidence for each PCa treatment modality. RESULTS: Of the
      196,914 individuals included in the study, 68,421 (34.7%) received ADT. Median
      (IQR) follow-up was 59 (29-95) months. Overall, a total of 2495 (1.3%)
      individuals developed BCa during follow-up. After stratification according to
      ADT, the 10-year cumulative incidence rate was 1.75% (95% CI 1.65-1.85). In the
      untreated group, the 10-year cumulative incidence rate was 1.99% (95% CI 1.83
      2.15). In multivariable competing-risk regression, the use of ADT was not
      associated with BCa, after accounting for the risk of dying from any cause (p =
      0.1). CONCLUSION: We failed to identify any impact of ADT on the risk of
      developing a subsequent BCa even after stratifying according to the type of
      treatment. Further studies are required to explain the gender gap in BCa
      incidence and outcomes.

PMID- 30276544
TI  - Pharmacological management of post-traumatic seizures in adults: current practice
      patterns in the UK and the Republic of Ireland.
AB  - BACKGROUND: Patient selection for seizure prophylaxis after traumatic brain
      injury (TBI) and duration of anti-epileptic drug treatment for patients with
      early post-traumatic seizures (PTS), remain plagued with uncertainty. In early
      2017, a collaborative group of neurosurgeons, neurologists, neurointensive care
      and rehabilitation medicine physicians was formed in the UK with the aim of
      assessing variability in current practice and gauging the degree of uncertainty
      to inform the design of future studies. Here we present the results of a survey
      of clinicians managing patients with TBI in the UK and Ireland. MATERIALS AND
      METHODS: An online survey was developed and piloted. Following approval by the
      Academic Committee of the Society of British Neurological Surgeons, it was
      distributed via appropriate electronic mailing lists. RESULTS: One hundred and
      seventeen respondents answered the questionnaire, predominantly neurosurgeons
      (76%) from 30 (of 32) trauma-receiving hospitals in the UK and Ireland. Fifty
      three percent of respondents do not routinely use seizure prophylaxis, but 38%
      prescribe prophylaxis for one week. Sixty percent feel there is uncertainty
      regarding the use of seizure prophylaxis, and 71% would participate in further
      research to address this question. Sixty-two percent of respondents use
      levetiracetam for treatment of seizures during the acute phase, and 42% continued
      for a total of 3 months. Overall, 90% were uncertain about the duration of
      treatment for seizures, and 78% would participate in further research to address
      this question. CONCLUSION: The survey results demonstrate the variation in
      practice and uncertainty in both described aspects of management of patients who
      have suffered a TBI. The majority of respondents would want to participate in
      future research to help try and address this critical issue, and this shows the
      importance and relevance of these two clinical questions.

PMID- 30276546
TI  - Letter to the editor: endoscopic transorbital route to the petrous apex: a
      feasibility anatomic study.

PMID- 30276547
TI  - Preclinical success but clinical failure of the sutureless excimer laser-assisted
      non-occlusive anastomosis (SELANA) slide.
AB  - BACKGROUND: The excimer laser-assisted non-occlusive anastomosis (ELANA) has been
      developed for intracranial bypass without the need for temporary recipient
      occlusion. We designed and tested a sutureless variant of the ELANA-the SELANA
      slide (SEsl). OBJECTIVE: This study aims to evaluate the SEsl preclinical results
      and describe its first clinical application. METHODS: First, in a cadaver study,
      28 SEsl anastomoses were compared with 28 ELANA anastomoses. Second, in an acute
      rabbit model, 90 SEsl anastomoses were compared with 30 ELANA anastomoses.
      Finally, in a surviving pig model, 38 SEsl bypasses were created. To evaluate the
      clinical efficacy of the SEsl, we then treated one patient with a giant, right
      sided middle cerebral artery (MCA) aneurysm with an intracranial-intracranial
      SEsl bypass and parent vessel occlusion. RESULTS: In preclinical studies, the
      SEsl anastomosis was shown to be equivalent or superior to the ELANA in terms of
      associated ease, patency, and bleeding complications. However, clinical
      application in rigid and arteriosclerotic receiving arteries was problematic.
      Although bypass creation and aneurysm occlusion were technically successful and
      the patient was postoperatively well, a pseudoaneurysm formed postoperatively at
      the internal carotid artery anastomosis and bled. Subsequent treatment failed and
      the patient did not survive. CONCLUSION: The SEsl showed promising preclinical
      results across three models. However, in its present form, it is not suitable for
      clinical application. TRIAL NUMBER: IRB UMCU 10/154.

PMID- 30276548
TI  - Hydroxyapatite cranioplasty: a retrospective evaluation of osteointegration in 17
      cases.
AB  - BACKGROUND: Cranial reconstruction with autologous bone is still the gold
      standard although several biomaterials are available to re-establish the
      integrity of the cranial vault. Due to their biological and morphological
      characteristics, hydroxyapatite implants show promising results in small clinical
      cohort studies, especially within the paediatric population. Its biocompatibility
      and osteoconductivity should allow the formation of osseous bridging at the skull
      prosthesis interface. OBJECTIVE: To examine the possible occurrence of
      osteointegration and to quantify it. METHODS: A retrospective study of patients
      with a hydroxyapatite implant from 2010 to 2014 at our neurosurgical department
      was conducted. Demographic, surgical and radiological data were studied. A senior
      neuroradiologist, a staff member neurosurgeon and a resident neurosurgeon
      independently performed the radiological evaluation. A new software analysis
      technique was developed to objectively quantify the degree of osteointegration.
      RESULTS: Seventeen implants were evaluated with an average patient age of 39
      years and a mean follow-up of 155 weeks. Through radiologic evaluation, osseous
      bridging was deemed higher than 50% in six prostheses and higher than 75% in
      three. In five patients, no osteointegration could be seen. The remaining
      patients exhibited sparse signs of osteointegration, estimated between 10 and
      50%. Software analysis showed an average osteointegration ratio of 37.4% with a
      400-HU filter and 27.3% with a 700-HU filter. CONCLUSION: In this small
      retrospective study of cranial hydroxyapatite implants, osteointegration did
      occur and to a degree of more than 50% in 1/3 of the patients.

PMID- 30276545
TI  - Filling the gap between the OR and virtual simulation: a European study on a
      basic neurosurgical procedure.
AB  - BACKGROUND: Currently available simulators are supposed to allow young
      neurosurgeons to hone their technical skills in a safe environment, without
      causing any unnecessary harm to their patients caused by their inexperience. For
      this training method to be largely accepted in neurosurgery, it is necessary to
      prove simulation efficacy by means of large-scale clinical validation studies.
      METHODS: We correlated and analysed the performance at a simulator and the actual
      operative skills of different neurosurgeons (construct validity). We conducted a
      study involving 92 residents and attending neurosurgeons from different European
      Centres; each participant had to perform a virtual task, namely the placement of
      an external ventricular drain (EVD) at a neurosurgical simulator
      (ImmersiveTouch). The number of attempts needed to reach the ventricles and the
      accuracy in positioning the catheter were assessed. RESULTS: Data suggests a
      positive correlation between subjects who placed more EVDs in the previous year
      and those who get better scores at the simulator (p = .008) (fewer attempts and
      better surgical accuracy). The number of attempts to reach the ventricle was also
      analysed; senior residents needed fewer attempts (mean = 2.26; SD = 1.11) than
      junior residents (mean = 3.12; SD = 1.05) (p = .007) and staff neurosurgeons
      (mean = 2.89, SD = 1.23). Scoring results were compared by using the Fisher's
      test, for the analysis of the variances, and the Student's T test. Surprisingly,
      having a wider surgical experience overall does not correlate with the best
      performance at the simulator. CONCLUSION: The performance of an EVD placement on
      a simulator correlates with the density of the neurosurgical experience for that
      specific task performed in the OR, suggesting that simulators are able to
      differentiate neurosurgeons according to their surgical ability. Namely this
      suggests that the simulation performance reflects the surgeons' consistency in
      placing EVDs in the last year.

PMID- 30276549
TI  - Low-dose aspirin treatment enhances the adhesion of preeclamptic decidual
      mesenchymal stem/stromal cells and reduces their production of pro-inflammatory
      cytokines.
AB  - Preeclampsia (PE) is a hypertensive disorder of human pregnancy. Low-dose aspirin
      (acetylsalicylic acid) (60-150 mg/day) is used to prevent PE when taken early in
      pregnancy. The effect of aspirin on term PE remains uncertain. Abnormal
      placentation is a hallmark of PE and leads to increased placental oxidative
      stress, which triggers the release of anti-angiogenic factors that cause local
      damage to the decidual vasculature. The damage subsequently spreads systemically
      and culminates in maternal clinical symptoms. Decidua basalis mesenchymal
      stem/stromal cells (DMSCs) reside in a vascular microenvironment. In PE, DMSCs
      are exposed to abnormally high levels of oxidative stress and circulating
      inflammatory factors from the maternal blood. We previously showed that colony
      forming unit ability and resistance to oxidative stress in DMSCs are reduced in
      MSCs derived from term PE pregnancies (PE-DMSCs). The action, if any, of aspirin
      on term PE-DMSCs has not been reported. In this study, aspirin (5 MUg/mL) was
      found to significantly increase PE-DMSC adhesion compared to untreated PE-DMSCs
      and gestation-matched control DMSCs (p value < 0.001) but had no effect on PE
      DMSC proliferation. ELISA analysis showed that aspirin significantly decreased
      the production of inflammatory cytokines IFN-gamma (p value < 0.05) and IL-8 (p
      value < 0.001) in PE-DMSCs. In addition, aspirin treatment increased the
      antioxidant capacity of PE-DMSCs compared with the untreated group (p value <
      0.05). This study is the first to reveal a novel, beneficial action of aspirin on
      PE-DMSCs from term PE pregnancies by improving their adhesion, suppressing their
      production of pro-inflammatory cytokines production, and increasing their
      antioxidant capacity. KEY MESSAGES: Preeclampsia (PE) is a serious hypertensive
      disorder of pregnancy. The risk of PE is reduced by aspirin but the mechanism is
      poorly understood. Decidua basalis mesenchymal stem/stromal cells (DMSCs) are
      abnormal in PE. Aspirin treatment improves multiple functions of PE-DMSCs.
      Improved DMSC function may contribute to the beneficial effect of aspirin.

PMID- 30276550
TI  - A fluorometric aptasensor for patulin based on the use of magnetized graphene
      oxide and DNase I-assisted target recycling amplification.
AB  - A fluorometric patulin (PAT) assay is presented that is based on the use of
      magnetic reduced graphene oxide (rGO) and DNase I. The fluorescence of the PAT
      aptamer labelled with 6-carboxyfluorescein (FAM) is quenched by magnetized
      reduced graphene oxide (rGO-Fe3O4) due to fluorescence resonance energy transfer
      (FRET). However, in the presence of PAT, the labelled aptamer is stripped off
      from rGO-Fe3O4. The rGO-Fe3O4 is then magnetically separated so that the
      fluorescence of free labelled PAT aptamer is restored. DNase I cannot hydrolyze
      the aptamer on rGO-Fe3O4, but it can cleave the free aptamer-PAT complex. This
      will release FAM and PAT which can undergo a number of additional cycles to
      trigger the cleavage of abundant aptamer. Recycling of DNase I-assisted target
      therefore leads to a strong amplification of fluorescence and consequently to an
      assay with low limit of detection. The detection limit for PAT is as low as 0.28
      MUg L-1 which is about 13 times lower than that without using DNase I. The method
      offers a new approach towards rapid, sensitive and selective detection based on
      an aptamer. Conceivably, it has a wide scope in that it may be applied to
      numerous other analytes if appropriate aptamers are available. Abstract Schematic
      of a fluorometric assay based on the use of magnetic graphene oxide and DNase I.
      It was applied to the determination of patulin. DNase I was introduced for
      recycling amplification. The detection limit is about 13 times lower than that
      without using DNase I. Figure a contains poor quality of text in image.
      Otherwise, please provide replacement figure file.Thank you. I will provide the
      figure file.

PMID- 30276551
TI  - CCL18 secreted from M2 macrophages promotes migration and invasion via the
      PI3K/Akt pathway in gallbladder cancer.
AB  - PURPOSE: The presence of M2 macrophages within primary tumors has been correlated
      with a poor prognosis for many types of cancer. However, little is known about
      the role of M2 macrophages in gallbladder cancer (GBC). METHODS: The number of M2
      macrophages in 78 GBC and 16 normal gallbladder tissue samples was assessed by
      immunohistochemistry. The THP-1 monocyte cell line was differentiated into M2
      macrophages and co-cultured with GBC-derived cell lines. The effect of M2
      macrophages on promoting GBC cell migration and invasion was analyzed using
      migration, invasion and scratch wound healing assays. Western blotting and real
      time PCR were used to assess the expression of epithelial-mesenchymal transition
      (EMT) markers and the activation status of the PI3K/Akt signaling pathway in GBC
      cells co-cultured with THP-1-derived macrophages. RESULTS: The average number of
      M2 macrophages was found to be significantly higher in GBC tissues than in normal
      gallbladder tissues. We also found that GBC patients with higher M2 macrophage
      counts exhibited poorer overall survival rates. Co-culture with M2 macrophages
      significantly promoted the migration, invasion and EMT of GBC cells. Moreover, we
      found that CCL18 secreted from M2 macrophages had the same effect on GBC cells as
      M2 macrophages. Blocking the function of CCL18 with a neutralizing antibody
      reversed this effect. Finally, we found that M2 macrophages could activate
      PI3K/Akt signaling in GBC cells, thereby leading to migration, invasion and EMT
      of these cells. CONCLUSIONS: Our findings contribute to our understanding of the
      role of chronic inflammation in GBC development and progression, and may offer
      potential therapeutic targets for GBC.

PMID- 30276552
TI  - Berberine attenuate staphylococcal enterotoxin B-mediated acute liver injury via
      regulating HDAC expression.
AB  - Staphylococcal enterotoxin B (SEB) has been documented to be implicated in the
      pathogenesis of liver injury in the experimental models of hepatitis. However,
      the underlying mechanism of SEB-induced acute liver injury (ALI) remains to be
      further explored. In our study, we explored the therapeutic effectiveness of
      berberine (BBR), a natural isoquinoline alkaloid, in the SEB-induced ALI. In our
      study, we found that injection of SEB into D-galactosamine (D-gal)-sensitized
      mice induced ALI, as demonstrated by an increase of levels of alanine
      aminotransferase and aspartate aminotransferase, massive infiltration of immune
      cells into the liver, and pro-inflammatory cytokine release. However,
      intragastric administration of BBR attenuated SEB-induced ALI in mice. Meanwhile,
      we discovered that BBR treatment suppressed activation of splenocytes and pro
      inflammatory cytokine release in SEB-stimulated splenocytes. Moreover,
      mechanistic analyses demonstrated that BBR was effective at inhibiting the
      expression of class I HDAC, but not class II, in SEB-stimulated splenocytes.
      Furthermore, trichostatin A, a standard HDAC inhibitor, alleviated activation of
      splenocytes and pro-inflammatory cytokine release in SEB-stimulated splenocytes.
      Taken together, we inferred from these results that BBR attenuated SEB-mediated
      ALI through repressing the class I HDAC enzyme, suggesting that BBR may
      constitute a novel therapeutic modality to prevent SEB-mediated inflammation and
      ALI.

PMID- 30276553
TI  - Bergenin: a computationally proven promising scaffold for novel galectin-3
      inhibitors.
AB  - Bergenin is a C-glycoside of 4-O-methylgallic acid that is isolated from
      medicinal plants such as Flueggea leucopyrus, Bergenia crassifolia, Mallotus
      philippensis, Corylopsis spicata, Caesalpinia digyna, Mallotus japonicus, and
      Sacoglottis gabonensis. Even though there appears to be ample evidence from South
      Asian traditional medicine that bergenin possesses strong anticancer activity, no
      comprehensive scientific study has been carried out to test its anticancer
      potency. Therefore, in this study, the potential mechanisms of action for
      bergenin's postulated anticancer activity were examined using computational
      techniques. Firstly, bergenin was tested for its toxicity as a drug candidate
      using in silico toxicity analysis. It was found that bergenin is nontoxic
      according to modern toxicity measures. The optimized structure of bergenin was
      obtained at the DFT-B3LYP/6-31G(d) level of theory. Potential biological targets
      of bergenin were identified using reverse docking calculations. Reverse docking
      results suggested that galectin-3 is a potential target of bergenin. Gelectin-3
      is an enzyme that plays a major role in cell-cell adhesion, cell-matrix
      interactions, macrophage activation, angiogenesis, metastasis, and apoptosis in
      cancer, making it a popular target in anticancer drug design. Among the many
      potential biological targets predicted by reverse docking calculations, galectin
      3 was selected as it complies with the primary objective of this study. The
      binding of bergenin to galectin-3 was studied by conventional forward docking
      calculations. Classical molecular dynamics (MD) simulations were used to study
      the stability of the galectin-3:bergenin complex. Docking calculations indicated
      that bergenin has the potential to effectively bind to the carbohydrate
      recognition domain (CRD) of galectin-3. As well as electrostatic and van der
      Waals interactions, a few strong hydrogen bonds were found to be involved in the
      binding of bergenin to galectin-3. There is also a plausible pi-stacking
      interaction between the aromatic moiety of bergenin and the His158 residue at the
      binding site. A 50-ns MD simulation was carried out for the bergenin:galectin-3
      complex in a cubic water box with periodic boundary conditions. The MD results
      showed that the bergenin:galectin-3 complex is highly stable and confirmed the
      veracity of the docking results, which suggested that bergenin potentially exerts
      an inhibitory effect on galectin-3. This study therefore sheds new light on the
      anticancer activity of bergenin and demonstrates that bergenin could potentially
      be used to develop more potent galectin-3 inhibitors. The study also provides
      scientific evidence supporting the use of bergenin-containing plants in cancer
      treatments in Eastern traditional medicine. Graphical abstract Bergenin in the
      galectin-3 binding site.

PMID- 30276554
TI  - Molecular Testing in EBUS-TBNA Specimens of Lung Adenocarcinoma: A Study of
      Concordance Between Cell Block Method and Liquid-Based Cytology in Appraising
      Sample Cellularity and EGFR Mutations.
AB  - PURPOSE: Cytological endobronchial ultrasound-guided transbronchial needle
      aspiration (EBUS-TBNA) specimens of mediastinal lymph node metastasis are
      frequently used to perform concomitant diagnosis, staging and genetic testing in
      non-small-cell lung cancer (NSCLC). The purposes of this single-center
      retrospective study were to evaluate EBUS-TBNA samples' adequacy for molecular
      testing of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase
      (ALK), and to analyze the concordance between the cell block method and liquid
      based cytology (LBC) in appraising the sample cellularity and in detecting EGFR
      mutation. MATERIALS AND METHODS: We retrospectively examined 82 patients who
      underwent EBUS-TBNA from October 2012 to September 2015 and received a confirmed
      diagnosis of lymph node metastasis of lung adenocarcinoma. Each sample was
      processed using both cell block and LBC to carry out DNA analysis (adequacy
      criterion: tumor cell percentage > 25%) and EGFR mutation testing. RESULTS: Fifty
      four patients were male, 66 were current or former-smokers, and the median age
      was 67 years. The median size of sampled lymph nodes was 14.8 mm. Seventy-one and
      66 samples were adequate to perform cell block and LBC, respectively. The kappa
      statistic (0.78) showed an excellent concordance. EGFR mutation was detected in
      eight patients using cell block and in seven using LBC, with a simple percentage
      agreement of 87.5%. ALK translocation was found in two patients. CONCLUSIONS:
      This study demonstrates the feasibility of EGFR mutation analysis with both cell
      block and LBC, with an excellent concordance between the two methods. Considering
      that the majority of advanced NSCLCs are diagnosed on cytology specimens, LBC is
      feasible and needs to be implemented for ancillary tests (immunocytochemistry,
      molecular analysis).

PMID- 30276555
TI  - Signal Detection Between Fluoroquinolone Use and the Risk of Rhegmatogenous
      Retinal Detachment: Sequence Symmetry Analysis Using Nationwide South Korean
      Healthcare Database Between 2004 and 2015.
AB  - BACKGROUND AND OBJECTIVES: The association between fluoroquinolone and
      rhegmatogenous retinal detachment (RRD) has been controversial as a result of
      inconsistent findings. We set out to detect a possible association of
      fluoroquinolone use and risk of RRD, using sequence symmetry analysis (SSA).
      METHODS: We conducted an SSA, case-only design, using a Korean nationwide
      healthcare database between 2004 and 2015. Exposure was defined as new
      fluoroquinolone use and outcome as an incident RRD, defined by a diagnosis of RRD
      (ICD-10: "H33.0") or surgery for RRD. Pairs of exposure and RRD within a 1-year
      time-window were included. The sequence ratio (SR) was calculated by the ratio of
      the number of patients prescribed with exposure first and diagnosed with RRD
      second divided by the number of patients diagnosed with RRD first and prescribed
      with exposure second. SR was adjusted (aSR) for underlying trends and 95%
      confidence intervals (CIs) were calculated. In order to observe whether the
      estimated ratio stabilized over time, we did repeated time-sequential analyses
      with the cumulative data starting from the 3-year period 2004-2006 to 2015.
      RESULTS: Fluoroquinolone use had a greater association with RRD as compared with
      other antibiotics [fluoroquinolone: 5234 pairs; aSR = 1.70 (95% CI 1.61-1.80),
      first-generation cephalosporin: 4139 pairs; aSR = 1.39 (95% CI 1.31-1.80), second
      generation cephalosporin: 5914 pairs; aSR = 1.31 (95% CI 1.24-1.38), third
      generation cephalosporin: 3650 pairs; aSR = 0.88 (95% CI 0.83-0.95), extended
      spectrum penicillin: 4823 pairs; aSR = 1.29 (95% CI 1.31-1.47), macrolides: 4115
      pairs; aSR = 1.31 (95% CI 1.24-1.39)]. Time-sequential analyses supported the
      association between fluoroquinolone and RRD. CONCLUSIONS: Our detection suggests
      a possible association between fluoroquinolone use and RRD. However, possible
      overestimation and reverse causality bias may have influenced our findings due to
      the limitation of an SSA design.

PMID- 30276557
TI  - A Nanometer Water Pump Induced by the Brownian and Non-Brownian Motion of a
      Graphene Sheet on a Membrane Surface.
AB  - Energy-saving water pump and efficient semipermeable membranes are the cores of
      reverse osmosis technology. Applying nanotechnology to improve the performance is
      a fashion in recent years. Based on the competitive effect of water's spontaneous
      infiltration of two sides of a carbon nanotube, we design a water pump that makes
      use of the natural permeability by weakening one side's competitiveness based on
      a small graphite sheet laying on the membrane. According to molecular dynamic
      simulations, continues net flux is observed. The motion mode of the sheet is the
      key for the performance. For the pure Brownian motion without any dynamical load,
      we find two water molecules per nanosecond flux, while the flux induced by the
      unidirectional motion can be several times enhanced, depending on the external
      force. The Brownian motion is similar to the physical mechanism of osmotic
      pressure, and the unidirectional motion shows great performance that has huge
      applications for reverse osmosis. Our work creatively proposes a new strategy to
      pump water molecules crossing though a nanochannel, inspiring for nanofluidic
      device designers.

PMID- 30276558
TI  - Luteolin suppresses inflammation through inhibiting cAMP-phosphodiesterases
      activity and expression of adhesion molecules in microvascular endothelial cells.
AB  - Luteolin, an anti-inflammatory ingredient found in the Chinese herb Folium
      perillae, can inhibit not only the cyclic adenosine monophosphate (cAMP)
      phosphodiesterases (PDEs) activity of neutrophils, but also the expression of
      lymphocyte function-associated antigen-1 in neutrophils, both of which result in
      a decrease in the adhesion between neutrophils and microvascular endothelial
      cells. However, the effect of luteolin on the cAMP-PDEs activity and expression
      of adhesion molecules in endothelial cells are not clear. In the present study,
      primary rat pulmonary microvascular endothelial cells and a lipopolysaccharide
      induced rat acute pneumonia model were used to explore the role of luteolin on
      cAMP-PDEs activity, expression of adhesion molecules, and leukocyte infiltration.
      We demonstrate that rat pulmonary microvascular endothelial cells expressed high
      levels of cAMP-PDEs, specifically PDE4, and further luteolin exhibited dose
      dependent inhibition on the activity of cAMP-PDEs or PDE4 in endothelial cells.
      Luteolin also had a significant inhibitory effect on the expression of vascular
      cell adhesion molecule (VCAM)-1, but not intracellular cell adhesion molecule
      (ICAM)-1 in microvascular endothelial cells. Further, we show that luteolin
      decreased the levels of soluble ICAM-1 (sICAM-1), but not soluble E-selectin in
      the serum of rats subjected to acute pneumonia. We also show that luteolin
      treatment decreased the wet/dry weight ratio of lung tissue and reduced the total
      number of serum leukocytes in a dose-dependent manner in a rat acute pneumonia
      model. In conclusion, these results demonstrate that luteolin suppresses
      inflammation, at least in part, through inhibiting both cAMP-PDEs or PDE4
      activity and the expression of VCAM-1 (in vitro) and sICAM-1 (in vivo) in
      endothelial cells.

PMID- 30276556
TI  - Improved bioethanol production using CRISPR/Cas9 to disrupt the ADH2 gene in
      Saccharomyces cerevisiae.
AB  - Bioethanol, as a form of renewable and clean energy, has become increasingly
      important to the energy supply. One major obstacle in ethanol production is
      developing a high-capacity system. Existing approaches for regulating the ethanol
      production pathway are relatively insufficient, with nonspecific genetic
      manipulation. Here, we used CRISPR/Cas9 technology to disrupt the alcohol
      dehydrogenase (ADH) 2 gene via complete deletion of the gene and introduction of
      a frameshift mutation in the ADH2 locus. Sequencing demonstrated the accurate
      knockout of the target gene with 91.4% and near 100% targeting efficiency. We
      also utilized genome resequencing to validate the mutations in the ADH2 mutants
      targeted by various single-guide RNAs. This extensive analysis indicated the
      mutations in the CRISPR/Cas9-engineered strains were homozygous. We applied the
      engineered Saccharomyces cerevisiae strains for bioethanol production. Results
      showed that the ethanol yield improved by up to 74.7% compared with the yield
      obtained using the native strain. This work illustrates the applicability of this
      highly efficient and specific genome engineering approach to promote the
      improvement of bioethanol production in S. cerevisiae via metabolic engineering.
      Importantly, this study is the first report of the disruption of a target gene,
      ADH2, in S. cerevisiae using CRISPR/Cas9 technology to improve bioethanol yield.

PMID- 30276560
TI  - Long-term clinical, radiological, and histological follow-up after complex
      ventral incisional hernia repair using urinary bladder matrix graft
      reinforcement: a retrospective cohort study.
AB  - BACKGROUND: Complex ventral incisional hernia repair represents a challenging
      clinical condition in which biologically derived graft reinforcement is often
      utilized, but little long-term data inform that decision. Urinary bladder matrix
      (UBM) has shown effectiveness in diverse clinical settings as durable
      reinforcement graft material, but it has not been studied over a long term in
      ventral incisional hernia repair. This study evaluates the clinical,
      radiographic, and histological outcome of complex incisional hernia repair using
      UBM reinforcement with 12-70 months of follow-up. METHODS: A single-arm,
      retrospective observational study of all ventral incisional hernia repairs
      utilizing UBM reinforcement over a 6-year time frame by a single surgeon was
      performed. Patients were assessed in long-term follow-up clinically and with the
      Carolina Comfort Scale. A subset of patients was assessed with abdominal wall
      ultrasound or CT scan. Three patients had abdominal wall fascial biopsies years
      after the incisional hernia repair with UBM graft, and the histology is analyzed.
      RESULTS: 64 patients underwent repair of complex incisional hernias with UBM
      graft reinforcement by a single surgeon. 42 patients had concomitant procedures
      including large or small bowel resection, excision of infected mesh, evacuation
      of abscess or hematoma, cholecystectomy, or panniculectomy with abdominoplasty.
      16 patients had ostomies at the time of repair. Median follow-up time is 36
      months, with a range of 12-70 months. Nine patients (14%) have required surgical
      repair of a recurrent hernia, and a tenth patient has a recurrence that is
      managed non-surgically, for a total recurrence rate of 15.6% over the entire time
      frame. Median time to recurrence was 32 months, and a Kaplan-Meier freedom from
      recurrence curve is depicted. 28 patients have undergone ultrasound or CT
      assessments of the abdominal wall which demonstrate radiographic fascial
      integrity 12-70 months after repair. Three patients have been re-explored for
      unrelated reasons in the years following ventral incisional hernia repair with
      UBM, and full thickness fascial biopsies demonstrate a robust remodeling response
      histologically similar to native myofascial tissue. No patients have developed
      graft infection, fistulization to the graft, or required graft explantation.
      Carolina Comfort Scale assessment of 45 patients 3 years after the repair
      averaged 16 out of a possible 115. CONCLUSION: In 64 patients undergoing complex
      ventral incisional hernia repair with UBM reinforcement, all have experienced
      successful resolution of complex clinical conditions and 15.6% of these repairs
      have recurred at a median follow-up of 3 years. Three full-thickness biopsies of
      the repaired fascia years later shed light on a promising remodeling response
      which may signal strength and durability comparable to native fascia.

PMID- 30276559
TI  - Increased Sputum IL-17A Level in Non-asthmatic Eosinophilic Bronchitis.
AB  - BACKGROUND: Non-asthmatic eosinophilic bronchitis (NAEB) is one common cause of
      chronic cough which is characterized as airway eosinophilic inflammation like
      asthma but lack of airway hyper-responsiveness. Previous studies showed that Th2
      pathway plays a role in NAEB, but the role of non-Th2 pathway in mechanism of
      NAEB remains unknown. Recently, IL-17A, a Th17-pathway cytokine, has been
      demonstrated to be involved in asthma development. However, the relationship
      between Th17-pathway and NAEB is unknown. METHODS: We aim to assess the airway
      level of IL-17A in the subjects with NAEB. Relationships between the IL-17A level
      and airway function in NAEB or asthma are also observed. We measured IL-17A
      concentrations in the sputum supernatant from 12 subjects with EB, 16 subjects
      with asthma [9 eosinophilic asthmatic (EA) and 7 non-eosinophilic asthmatic (NEA)
      according to the sputum eosinophil >= 3%], and 9 healthy control subjects.
      RESULTS: Increasing IL-17A level was found in NAEB group (29.65 +/- 8.13 pg/ml),
      EA group (32.45 +/- 3.22 pg/ml), and NEA group (29.62 +/- 6.91 pg/ml) compared
      with the healthy control group (17.05 +/- 10.30 pg/ml) (P < 0.05, P < 0.01, P <
      0.05, respectively). The sputum IL-17A level was correlated with FENO (r = 0.44,
      P < 0.01), FEV1/FVC% (r = - 0.38, P < 0.05), MMEF%pred (r = - 0.34, P < 0.05),
      and sputum neutrophil% (r = 0.33, P < 0.05) in total. CONCLUSION: Th17-pathway
      may play a role not only in asthmatics, but also in subjects with NAEB, as
      reflected by increasing IL-17A concentrations in sputum supernatant.

PMID- 30276562
TI  - The role of personality in patients with fibromyalgia.
AB  - Previous studies suggest personality, the multifaceted characteristics underlying
      a person's affect, cognition, and behavior, may influence fibromyalgia. We
      examined associations among personality, fibromyalgia impact, and health-related
      outcomes in patients with fibromyalgia. We further tested whether anxiety and
      depression mediated the effect of personality on fibromyalgia impact. We
      performed a secondary analysis using baseline data from a randomized trial on
      fibromyalgia. Personality was assessed using the NEO-Five Factor Inventory 3.
      Fibromyalgia impact was evaluated using the revised Fibromyalgia Impact
      Questionnaire (FIQR). We also measured symptom severity, anxiety, depression,
      stress, quality of life, social support, self-efficacy, outcome expectations, and
      mindfulness. Multivariable linear regression was performed to evaluate each
      association. Mediation analysis assessed whether anxiety and depression mediated
      the relationship between personality and FIQR. There were 92 participants, 95%
      female, mean age 52 years, body mass index (BMI) 30 kg/m2, 52% white, and mean
      duration of body pain 14 years. Higher neuroticism was significantly associated
      with higher FIQR (P = 0.002) and symptom severity (P = 0.008), as well as higher
      levels of anxiety, depression and stress, worse mental component quality of life,
      and lower self-efficacy, mindfulness, and social support. Higher
      conscientiousness and extraversion were associated with better psychological
      health and health-related outcomes. The effect of neuroticism on fibromyalgia
      impact was mediated by anxiety and depression. Personality was associated with
      fibromyalgia impact and a variety of health outcomes. Identifying the factors
      that influence fibromyalgia will help us better understand the condition and
      provide insight for more effective treatment.

PMID- 30276561
TI  - Surgical site infection: the "Achilles Heel" of all types of abdominal wall
      hernia reconstruction.
AB  - PURPOSE: Surgical site infection is the most common hospital-acquired infection
      in surgical patients. Recently, public health organizations have updated
      prevention guidelines. This review discusses surgical site infections as a
      complication of abdominal wall reconstruction. METHODS: The authors reviewed
      guidelines on prevention of surgical site infections from the Center for Disease
      Control and Prevention, World Health Organization, and National Institute for
      Health and Care Excellence and put them into context with the relevant abdominal
      wall reconstruction literature. This was the subject of the Nyhus-Wantz lecture
      given at The International Hernia Congress on March 14, 2018 in Miami, FL and is
      summarized here. RESULTS: Routine use of preoperative antibiotics in prosthetic
      groin hernia repair is not supported by the available literature. High-quality
      data on antibiotic prophylaxis in ventral (both primary and incisional) hernia
      repair is lacking, but it is widely utilized and may reduce SSIs. Recommended
      preventative strategies discussed in this manuscript include: treatment of remote
      site infections, perioperative normothermia and normoglycemia, avoidance of
      hypoxemia, antiseptic preparation of surgical team hands and patient skin,
      treatment of obesity, smoking cessation, correction of malnutrition, and physical
      conditioning. CONCLUSION: Surgical site infections lead to significant morbidity
      and mortality, hernia recurrences, prolonged hospital stay, and increased
      hospital costs. This makes surgical site infections the "Achilles Heel" of
      abdominal wall reconstruction. Strict adherence to standardized guidelines and
      preoperative optimization of patients' risk profiles are crucial to decrease the
      incidence of surgical site infections.

PMID- 30276564
TI  - [From volunteer work to critical care paramedic : The history of an ongoing
      process of professionalisation].
AB  - BACKGROUND: For 4 years, the profession of critical care paramedic has been
      established in Germany. As a result, nonmedical rescue service personnel receive
      a 3-year apprenticeship for the first time. This also led to a revaluation of
      functions and responsibilities within this occupational field. OBJECTIVES: Which
      medical and social processes contributed to the establishment of the occupational
      profile of a critical care paramedic? How did training methods change over the
      last 50 years and which debates helped to shape the development of the
      occupational field? MATERIALS AND METHODS: The article at hand is based on an
      interpretation of archival primary sources of the parties observed. Moreover, it
      is also predicated on a qualitative content analyses of the secondary literature
      focusing on the subject area of nonmedical rescue service personnel. RESULTS: In
      the 1960s, a professionalisation process for paramedics was initiated after
      realising that rapid medical treatment on location can have a positive impact on
      the healing process. The debate on the training for paramedics has been
      influenced by longstanding negotiations between different parties about the
      question of which tasks could be ascribed to nonmedical rescue service personnel.
      CONCLUSIONS: In the larger context, the discussions about the tasks of critical
      care paramedics are centered around the question of delegation and, respectively,
      the substitution of medical tasks usually assigned to physicians. The
      academization of the profession that is currently emerging will continue to lead
      to conflicts with the medical profession.

PMID- 30276563
TI  - Severe thrombocytopenia in connective tissue diseases: a single-center review of
      131 cases.
AB  - To analyze the clinical characteristics of severe thrombocytopenia in patients
      with various connective tissue diseases (CTDs), one hundred thirty-one
      consecutive CTD patients with blood platelet count less than 20 * 109/L on
      admission, which was ascribed to the nature of diseases, during January 2011 to
      June 2015 in our department were enrolled and checked for their survival status
      in September 2015. The patients were categorized based on background diseases or
      therapeutic effects, and compared with clinical features, treatment strategies,
      and long-term outcomes among the groups. Cumulative survival rates were estimated
      using Kaplan-Meier analysis. Of the patients, 88.5% were female. The most
      frequently seen background diseases were primary Sjogren's syndrome (pSS) (53.4%)
      and systemic lupus erythematosus (SLE) (40.5%). Age on admission for SLE patients
      (36.7 +/- 14.1 years) was much younger than that for other patients (44.4 +/-
      15.4 years for pSS and 46 +/- 16.1 years for other CTDs, p < 0.05). Ninety-six
      cases accompanied with various bleeding symptoms, which were more common in pSS
      patients than in SLE patients (80.0% vs. 64.2%, p < 0.05). Glucocorticoids and/or
      intravenous immunoglobulin were applied as initial therapy with an overall
      response rate of 36.6%. For patients failed to respond, immunosuppressive drugs
      were added and the other 22.8% benefited from the treatment. Compared to those
      ineffective to the aforementioned drugs, patients with therapeutic effects had
      significantly high immunoglobulin G levels. Twenty patients with refractory
      diseases accepted mesenchymal stem cell transplantation (MSCT) with a total
      effective rate of 65.0%. Eleven patients died after the follow-up for a mean time
      of 27.7 months, of which 7 were associated with hemorrhage. There was no
      difference in the survival rate among different background diseases. However,
      compared with those who did not gain remission, patients achieved partial or
      complete remission had better cumulative survival rates (p < 0.01). In
      conclusion, among various CTDs, severe thrombocytopenia often occurs in patients
      with SLE or pSS. Early response to the treatments, but not the background
      disease, is an important predictor of long-term prognosis. For patients with
      refractory thrombocytopenia, MSCT may provide an alternative therapeutic
      strategy.

PMID- 30276565
TI  - Prediction of ICU mortality in critically ill children : Comparison of SOFA, GCS,
      and FOUR score.
AB  - INTRODUCTION: The SOFA (Sequential Organ Failure Assessment), GCS (Glasgow Coma
      Scale), and FOUR (Full Outline of UnResponsiveness) scores are the most commonly
      used scoring systems to predict the risk of mortality and morbidity in intensive
      care units (ICUs). The aim of the current study was to compare the predictive
      ability of these three models for predicting medical/surgical ICU mortality in
      critically ill children. METHODS: In the current observational and prospective
      study, a total of 90 consecutive patients, age <=18 years, admitted to medical
      and surgical ICUs, were enrolled. The SOFA, GCS, FOUR score and demographic
      characteristics of all children were recorded on the first day of admission. For
      statistical analyses, a receiver operator characteristic (ROC) curve, the Hosmer
      Lemeshow goodness of fit test, and logistic regression were used (95% confidence
      interval). RESULTS: The SOFA, GCS, and FOUR scores between survivors and
      nonsurvivors were statistically different (p = 0.002, p < 0.001, p = 0.004,
      respectively). The discrimination power for SOFA, GCS, and FOUR score was
      moderate (area under ROC [AUC] curve: 75.1%; standard error [SE]: 6.0%, 72.9%
      [SE: 7.2%], 78.7% [SE: 6.6%], respectively). The only well-calibrated model was
      GCS (x2 = 2.76, p = 0.59). CONCLUSIONS: The performance of the three predictive
      models SOFA, GCS, and FOUR score for predicting outcomes in children admitted to
      medical and surgical ICUs was good. The discrimination was moderate for all three
      models, and calibration was good just for GCS. GCS was superior in predicting
      outcome in critically ill children; however, further studies are needed to
      validate these scores in the pediatric population.

PMID- 30276566
TI  - [Multidrug-resistant bacteria in animals and humans].
AB  - BACKGROUND: The increasing burden of antimicrobial-resistant bacteria causes
      morbidity and mortality, especially among patients affected by healthcare
      associated infections. Limited treatment options challenge clinicians in both
      human and veterinary medicine. OBJECTIVES: To summarize current evidence for the
      occurrence of antimicrobial-resistant bacteria and their zoonotic transmission
      between humans and animals with a focus on data from Germany. MATERIALS AND
      METHODS: Review of scientific literature and publications from German national
      public health institutions. RESULTS AND CONCLUSIONS: Methicillin-resistant
      Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL)
      producing Enterobacteriaceae are frequently transmitted between animals and
      humans. The rates of asymptomatic carriage are increased among persons with
      livestock contact compared with the general population. The occurrence of
      carbapenemase-producing Enterobacteriaceae has been documented on German pig and
      chicken farms, but investigations into their prevalence and zoonotic importance
      are pending. Colistin is frequently used in veterinary medicine to treat
      diarrhoea and causes selection pressure for colistin-resistant Gram-negative
      bacteria harbouring mcr genes. Vancomycin-resistant enterococci (VRE),
      oxazolidinone-resistant Gram-positive bacteria and multiresistant staphylococci
      are further antimicrobial-resistant microorganisms, which might have a zoonotic
      potential. Besides human healthcare and livestock, the problem of antimicrobial
      resistant bacteria also affects companion animals (e. g. dogs, cats and horses),
      wildlife and the environment, which underlines the need to prevent antimicrobial
      resistance in a One Health approach.

PMID- 30276567
TI  - Letter to the Editor: Acid Reflux or Non-acid Reflux?

PMID- 30276568
TI  - Creeping Fat Assessed by Small Bowel MRI Is Linked to Bowel Damage and Abdominal
      Surgery in Crohn's Disease.
AB  - BACKGROUND: Crohn's disease (CD) leads to bowel damage and surgery in a
      significant proportion of patients. AIMS: The aim of the study was to evaluate
      the predictive value of creeping fat assessed by small bowel MRI in CD patients.
      METHODS: CD patients undergoing small bowel MRI were included in a retrospective
      observational cohort study. Clinical findings were extracted and correlated with
      radiological outcome measures. Logistic regression analysis was performed to
      assess predictors associated with a complicated course and surgery within 2 years
      and long-term follow-up. RESULTS: Ninety patients (49% female, median follow-up
      93 months) were included. Creeping fat was identified in 21.1%. Of these
      patients, 68% and 79% developed bowel damage (p < .05) and 42% and 63% of
      patients revealing creeping fat underwent surgery within 2 years following MRI
      and total follow-up, respectively. The presence of creeping fat [odds ratio (OR)
      4.0], inflammatory stenosis (OR 3.7), multisegmental (small) bowel (OR 4.5 and
      3.8), and proximal small bowel inflammation (OR 5.0) were associated with
      inferior outcome (p < .05) in a univariate analysis. Creeping fat was
      independently associated with a disabling course, bowel damage, and surgery (OR
      3.5 each, p < .05) in a multivariate analysis model. CONCLUSION: Creeping fat
      identified by small bowel MRI is associated with a complicated course and
      abdominal surgery in CD. Our data adds evidence that small bowel MRI facilitates
      risk stratification in order to define a patient at risk of disease-related
      complications in CD. [DRKS00011727, www.germanctr.de/ ].

PMID- 30276569
TI  - Sodium Butyrate Enhances Intestinal Riboflavin Uptake via Induction of Expression
      of Riboflavin Transporter-3 (RFVT3).
AB  - BACKGROUND: Uptake of riboflavin (RF) by intestinal epithelial cells occurs via a
      specific carrier-mediated process that involves the apically localized RF
      transporter-3 (RFVT3). Previous studies have shown that sodium butyrate (NaB)
      affects intestinal uptake of other substrates and expression of their membrane
      transporters, but its effect on intestinal uptake of RF and expression of RFVT3
      has not been examined. AIMS: To investigate the effect of NaB on intestinal RF
      uptake process and expression of the RFVT3. METHODS: Two experimental models were
      used in this study: Human-derived intestinal epithelial Caco-2 cells and ex vivo
      mouse colonoids. 3H-RF uptake assay, Western blot, RT-qPCR, and chromatin
      immunoprecipitation assay were performed. RESULTS: Treating Caco-2 cells with NaB
      led to a significant increase in carrier-mediated RF uptake. This increase was
      associated with a significant induction in the level of expression of the hRFVT3
      protein, mRNA, and heterogenous nuclear RNA (hnRNA). Similarly, treating mouse
      colonoids with NaB led to a marked increase in the level of expression of the
      mRFVT3 protein, mRNA, and hnRNA. NaB did not affect hRFVT3 mRNA stability, rather
      it caused significant epigenetic changes (histone modifications) in the SLC52A3
      gene where an increase in H3Ac and a reduction in H3K27me3 levels were observed
      in the NaB-treated Caco-2 cells compared to untreated controls. CONCLUSION: These
      findings demonstrate that NaB up-regulates intestinal RF uptake and that the
      effect appears to be mediated, at least in part, at the level of transcription of
      the SLC52A3 gene and may involve epigenetic mechanism(s).

PMID- 30276570
TI  - Differences in Prevalence of Large Polyps Between Hispanic Americans from Mexican
      and Non-Mexican-Predominant States.
AB  - BACKGROUND: There have been conflicting reports comparing the prevalence of large
      polyps (>9 mm) between Hispanics and non-Hispanic whites (NHW). Differences
      between Hispanic subpopulations may account for these variations. AIMS: We aimed
      to assess the prevalence of large polyps (>9 mm) in Hispanics from Mexican- and
      non-Mexican-predominant states compared with NHW. As secondary outcome, we
      evaluated results by polyp location. METHODS: The 2010 U.S. Census Bureau was
      used to identify states with a predominantly Mexican Hispanic (West) versus non
      Mexican Hispanic (East) populations. Average-risk colonoscopies in those states
      from 2001 to 2014 were accessed using the Clinical Outcomes Research Initiative
      database. Military and Veteran's Administration sites were excluded. Hispanics
      were compared with NHW in each geographical location using hierarchical logistic
      regression analysis. RESULTS: A total of 65,138 procedures were included with
      33,425 procedures in the West (14.5% Hispanics) and 31,713 procedures in the East
      (44.0% Hispanics,). East Hispanics had significantly less odds of large polyps,
      OR 0.74, CI 0.58-0.94, p = 0.02, while West Hispanics exhibited no difference, OR
      0.91, CI 0.76-1.10, p = 0.33, compared with NHW. Eastern Hispanics had less odds
      of large distal polyps, OR 0.69, CI 0.52-0.91, p = 0.01, and no difference in
      proximal polyps compared with NHW. Among Western Hispanics, no differences were
      seen in proximal, OR 1.06, CI 0.83-1.35, p = 0.66, or distal polyps, OR 0.83, CI
      0.68-1.02, p = 0.08, compared with NHW. CONCLUSION: Using NHW as a reference,
      Hispanics from Mexican-predominant states have a similar prevalence of large
      polyps, while Hispanics from non-Mexican-predominant states have a lower
      prevalence. Differences in Hispanic subpopulations likely explain previous
      conflicting reports on the prevalence of large polyps in Hispanics and NHW.

PMID- 30276573
TI  - The inhibition of thymidine phosphorylase can reverse acquired 5FU-resistance in
      gastric cancer cells.
AB  - BACKGROUND: 5FU can be converted to its active metabolite fluoro-deoxyuridine
      monophosphate (FdUMP) through two pathways: the orotate phosphoribosyl
      transferase-ribonucleotide reductase (OPRT-RR) pathway and the thymidine
      phosphorylase-thymidine kinase (TP-TK) pathway. We investigated the mechanism
      underlying 5FU-resistance, focusing on the changes in the 5FU metabolisms.
      METHODS: MKN45 and 5FU-resistant MKN45/F2R cells were treated with 5FU or fluoro
      deoxyuridine (FdU) in combination with hydroxyurea (HU) or tipiracil (TPI). The
      amount of FdUMP was determined by the density of the upper band of thymidylate
      synthase on Western blotting. RESULTS: The MKN45/F2R cells exhibited 5FU
      resistance (37.1-fold) and showed decreased OPRT and increased TP levels. In both
      cells, the FdUMP after treatment with 5FU was decreased when RR was inhibited by
      HU but not when TP was inhibited by TPI. A metabolome analysis revealed the loss
      of intracellular deoxyribose 1-phosphate (dR1P) in both cells, indicating that
      FdUMP was synthesized from 5FU only through the OPRT-RR pathway because of the
      loss of dR1P. After the knockdown of TK, the FdUMP after treatment with FdU was
      decreased in MKN45 cells. However, it was not changed in MKN45/F2R cells.
      Furthermore, TP inhibition caused an increase in FdUMP after treatment with 5FU
      or FdU and reversed the 5FU resistance in MKN45/F2R cells, indicating that FdUMP
      was reduced through the TP-TK pathway in MKN45/F2R cells. CONCLUSIONS: In
      MKN45/F2R cells, the reduction of FdUMP through the TP-TK pathway caused 5FU
      resistance, and the inhibition of TP reversed the resistance to 5FU, suggesting
      that the combination of 5FU and TPI is a promising cancer therapy.

PMID- 30276571
TI  - Utility of Esophageal High-Resolution Manometry in Clinical Practice: First, Do
      HRM.
AB  - Esophageal high-resolution manometry (HRM) has advanced the understanding of
      esophageal motor function and the ability to diagnose and manage disorders of
      esophageal motility. In this review, we describe the indications for and the
      technical performance of HRM. The Chicago classification of esophageal motor
      function, now in its third iteration, streamlines and standardizes the
      nomenclature and basic interpretation of HRM data depicted as Clouse topographic
      plots. In clinical practice, HRM is an important diagnostic test for patients
      with dysphagia as well as patients with suspected gastroesophageal reflux disease
      (GERD), particularly in those patients with a suboptimal symptomatic response to
      antisecretory therapy. HRM can support diagnoses such as achalasia, as well as
      provide evidence for behavioral disorders such as rumination syndrome or
      supragastric belching with the assistance of postprandial HRM with impedance.
      Further, the GERD classification of motor function introduces a three-part
      hierarchical evaluation of esophageal motor function in GERD, highlighting the
      value of assessment of esophageal contractile reserve through provocative
      maneuvers during HRM such as multiple rapid swallows.

PMID- 30276574
TI  - Body composition assessment and sarcopenia in patients with gastric cancer: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: There has recently been increased interest in the assessment of
      body composition in patients with gastric cancer for the purpose of
      prognostication. This systematic review and meta-analysis aim to evaluate the
      current literature on body composition assessment in patients with gastric cancer
      and its impact on peri-operative outcomes. METHODS: A systematic literature
      search was conducted for studies reporting assessment of body composition in
      patients with gastric cancers. Meta-analysis of postoperative outcomes (overall
      and major complications, anastomotic leaks, pulmonary complications) and survival
      was performed using random effects models. RESULTS: Thirty-nine studies reported
      the assessment of body composition in 8402 patients. Methods used to assess body
      composition in patients with gastric cancers were computerized tomography (n =
      26), bioelectrical impedance analysis (n = 9), and dual-energy-X-ray
      absorptiometry (n = 3). Only 21 studies reported the impact of pre-operative
      sarcopenia on post-operative outcomes. Sarcopenic patients have significantly
      higher rates of postoperative major complications (n = 12, OR 1.67, CI95% 1.14
      2.46, p = 0.009), and pulmonary (n = 8, OR 4.01, CI95% 2.23-7.21, p < 0.001)
      complications after gastrectomy. Meta-analysis of nine studies reporting overall
      survival after gastrectomy identified significantly worse survival in patients
      with pre-operative sarcopenia (HR 2.12, CI95% 1.89-2.38, p < 0.001). CONCLUSIONS:
      Assessment of body composition has the potential to become a clinically useful
      tool that could support decision-making in patients with gastric cancer. However,
      variation in methods of assessing and reporting body composition in this patient
      group limits assessment of current post-operative outcomes.

PMID- 30276572
TI  - Identification and characterization of N-glycosylation site on a Mucor
      circinelloides aspartic protease expressed in Pichia pastoris: effect on
      secretion, activity and thermo-stability.
AB  - Methylotrophic yeasts have widely been used as model organisms for understanding
      cellular functions and biochemical activities in lower eukaryotes. The gene
      encoding an aspartic protease (MCAP) from Mucor circinelloides DSM 2183 was
      cloned and expressed into Pichia pastoris using both the native M. circinelloides
      signal peptide (mcSP) and alpha-factor secretion signal from Saccharomyces
      cerevisiae (alpha-MF). When expressed in P. pastoris using alpha-MF and mcSP,
      MCAP was secreted into the culture medium at a concentration 200 mg L-1 (410 MCU
      mL-1) and 110 mg L-1 (249 MCU mL-1), respectively. The SDS-PAGE analysis of each
      culture shows that the protein was secreted in the media in two forms with
      molecular weights of approximately 33 and 37 kDa. Upon digestion using
      endoglycosidase H (Endo H), only one band at 33 kDa was observed, indicating that
      the protein might be glycosylated. One putative N-glycosylation site was found
      and a site-directed mutagenesis at position Asn331-Gln of the sequence produce
      only one form of the protein of 33 kDa, similar to that obtained when digested
      with Endo H. The optimum temperature and pH activity of the expressed MCAP was
      found to be at 60  degrees C and 3.6, respectively.

PMID- 30276575
TI  - Olfactory function in patients after transsphenoidal surgery for pituitary
      adenomas-a short review.
AB  - Olfaction is an important sensory input that obviously affects many daily
      activities. However, olfactory dysfunction (hyposmia and anosmia) leads to a
      pronounced decrease in quality of life. Surprisingly, little attention has been
      paid to olfactory changes after transsphenoidal surgery for pituitary tumors. In
      this review, we summarize current knowledge of the effects of transsphenoidal
      pituitary surgery on olfaction and compare different surgical techniques. Based
      on selected studies, the endoscopic approach, in comparison with the microscopic
      approach, seems to be superior in terms of preservation of olfactory function,
      although the quality of data from these studies is generally poor. The best
      results were observed when the endoscopic approach was used without harvesting of
      the nasoseptal flap.

PMID- 30276576
TI  - Rapid de-adhesion of northern pike Esox lucius eggs using sodium hypochlorite.
AB  - The elimination of egg stickiness is required for effective artificial
      reproduction of northern pike, but until now, available methods have required at
      least 40 min. Sodium hypochlorite was tested under laboratory conditions, and
      exposure to aqueous concentrations of 0.025-0.05% for 40 s effectively eliminated
      stickiness without adverse effects. Fertilization and hatching rates in
      laboratory trials were similar to those observed in eggs treated with traditional
      methods using clay or milk for 40 or 60 min, respectively, as well as those
      without treatment. Testing using conventional hatchery incubation techniques did
      not reveal differences in fertilization rates, while the number of hatched larva
      was significantly higher in eggs treated with sodium hypochlorite vs. clay. Eggs
      treated with sodium hypochlorite retained transparency, which facilitated
      monitoring of embryo development.

PMID- 30276577
TI  - Molecular identification of dmrt1 and its promoter CpG methylation in correlation
      with gene expression during gonad development in Culter alburnus.
AB  - Dmrt1, a member of the Dmrt family, is an important transcription regulator of
      gender determination. To study the biological function of dmrt1 in sexual
      differentiation and its potential implication in breeding technology, we obtained
      the full-length cDNA and proximal promoter sequence of dmrt1 in Culter alburnus,
      and analyzed the impact of promoter CpG methylation on the gene expression
      pattern of dmrt1 during gonad development. Dmrt1 was 922 bp in length and
      consisted a 150 bp 5'-UTR, a 28 bp 3'-UTR, and a 744 bp open reading frame (ORF).
      Based on the coding sequence of the dmrt1 gene, the deduced amino acid sequence
      was detected, and the protein structure of this gene was predicted in C.
      alburnus. The results indicate that the structure and function of dmrt1 were
      highly conservative compared to other vertebrates. The expression level of dmrt1
      mRNA in different tissues was explored by qRT-PCR, which was only highly
      expressed in the testes and almost undetectable in other tissues. The CpG
      methylation pattern of the dmrt1 promoter was studied using DNA sequencing of
      sodium bisulfite in adult testes and ovaries, and it was found that dmrt1
      promoter CpGs were not methylated in the testes, whereas hypermethylated in the
      ovaries. These findings demonstrate that DNA methylation can regulate sexual
      dimorphic expression of dmrt1, and therefore epigenetic modifications may play a
      critical role in the gonad differentiation of C. alburnus.

PMID- 30276578
TI  - Effects of multiwalled carbon nanotubes and carbofuran on metabolism in Astyanax
      ribeirae, a native species.
AB  - The study of the toxic effect of carbofuran and multiwalled carbon nanotubes
      (MWCNTs) on Astyanax ribeirae metabolism is of paramount importance due to the
      increasing use of this pesticide in agriculture and in the production of
      nanotubes within the material industry. This study aimed to evaluate the effects
      of carbofuran, MWCNT, and the combination of these compounds on specific oxygen
      consumption and excretion of ammonia in A. ribeirae. Therefore, 65 fish were
      divided into three groups of treatments at varying concentrations: carbofuran
      (0.01, 0.05, 0.1, and 0.5 mg/L), MWCNT (0.1, 0.25, 0.5, and 1.0 mg/L), and 0.5
      mg/L of MWCNT added to carbofuran concentrations (0.01, 0.05, 0.1, and 0.5 mg/L).
      The average specific oxygen consumption in the groups exposed to carbofuran,
      compared to the control, increased 73.49% at the 0.01 mg/L concentration and
      decreased 63.86% and 91.57% with treatments of 0.1 and 0.5 mg/L, respectively.
      For groups exposed to the MWCNT, there was an 83.91% drop with the 1.0 mg/L
      treatment, and the carbofuran + MWCNT groups recorded a decrease of 71.09%,
      92.77%, and 93.98% at concentrations of 0.05, 0.1, and 0.5 mg/L, respectively. In
      relation to specific ammonia excretion, in groups exposed to carbofuran compared
      to the control, there was an increase of 134.37% and 200% with the 0.1 and 0.5
      mg/L treatments, respectively. The group exposed to carbofuran + MWCNT
      experienced a decrease of 60% and 80% with treatments of 0.1 mg/L carbofuran +
      0.5 mg/L MWCNT and 0.5 mg/L carbofuran + 0.5 mg/L MWCNT, respectively. Therefore,
      it was concluded that carbofuran + MWCNT interact, increasing the effects in
      Astyanax sp.

PMID- 30276579
TI  - Effect of diphenyliodonium hexafluorophosphate salt on experimental infiltrants
      containing different diluents.
AB  - Non-invasive treatments for caries lesions are increasingly required for oral
      health; resin infiltration is one possible conservative option. In this study, we
      evaluated the effects of diphenyliodonium hexafluorophosphate salt (DPI) on
      experimental resin infiltrants with either (hydroxyethyl)methacrylate (HEMA) or
      ethanol as the diluent. A monomeric base with diglycidyl methacrylate ethoxylated
      (BisEMA, 25 wt%) and triethylene glycol dimethacrylate (TEGDMA, 75 wt%), 0.5 mol%
      of camphorquinone, and 1 mol% of ethyl-4-(dimethylamino)benzoate (EDAB) was
      prepared. The mixtures were divided into 12 groups according to DPI concentration
      (0; 0.25; 0.5; 1 mol%) and diluents (10 wt% HEMA, 10 wt% ethanol, or none).
      Degree of conversion (DC), water sorption (Ws), solubility (Sol), contact angle
      (CA), and cohesive strength (CS) tests were performed and compared to a
      commercial infiltrant control group (Icon). Only ethanol negatively affected DC
      and Sol, but both diluents negatively affected Ws and CS. Nevertheless, the
      presence of DPI, mainly at the 0.5 mol% concentration, compensated for the
      negative effects of the diluents. The commercial control group was less effective
      only for CS. In conclusion, 0.5% DPI seems to be the most suitable concentration
      to compensate for the negative effects of diluents.

PMID- 30276580
TI  - Influence of the final irrigation solution on the push-out bond strength of
      calcium silicate-based, epoxy resin-based and silicone-based endodontic sealers.
AB  - The aim was to evaluate the influence of different irrigation solutions on the
      push-out bond strength (POBS) of three different sealers (AH Plus, BioRoot RCS,
      GuttaFlow2). Root canals of 180 single-rooted human teeth were instrumented with
      F360 up to size 45.04. All canals were irrigated with 5 ml NaOCl 3% and 5 ml EDTA
      17%. The canals were finally irrigated with either 5 ml NaOCl 3%, CHX 2%, EDTA
      17%, citric acid 20% or NaCl 0.9% (n = 36) with a contact time of 5 min and
      obturated using matching gutta-percha cones according to the single-cone
      technique in combination with one of the sealers (n = 12). After 8 weeks of
      incubation, the roots were embedded in resin. Two slices of 1 mm thickness were
      obtained representing the middle third of the root. Dislodgement resistance was
      measured and POBS was calculated. Specimens were examined under 4* magnification
      to determine the mode of bond failure. Statistical analysis was performed using
      two-way ANOVA and Student-Newman-Keuls test for POBS and Chi-square test for the
      mode of failure. POBS was significantly affected by the factor "sealer" (P <
      0.001) and by the interaction "sealer/irrigation solution" (P < 0.01). AH Plus
      revealed significantly higher POBS than BioRoot RCS and GuttaFlow2 (P < 0.05).
      The POBS of GutttaFlow2 was not affected by the irrigation protocol (P > 0.05).
      The POBS of AH Plus was positively influenced by EDTA and NaOCl. EDTA had a
      negative effect on the POBS of BioRoot RCS. The POBS of GuttaFlow2 was not
      influenced by the irrigation solutions.

PMID- 30276581
TI  - Herbert Macgregor (1933-2018).

PMID- 30276584
TI  - Sensitive and specific assay for the simultaneous detection of Mycoplasma
      genitalium and macrolide resistance-associated mutations.
AB  - Patients infected by Mycoplasma genitalium are often treated empirically with the
      macrolide azithromycin. Macrolide resistance is becoming quite common; empirical
      treatment is compromised. Sequencing was initially used to detected azithromycin
      resistance-associated mutations. As this was laborious, qPCRs have been developed
      for their detection. In the present study, we describe a fast, sensitive, and
      specific qPCR assay that enables routine testing of M. genitalium and macrolide
      resistance-associated mutations in a single assay. M. genitalium positive
      clinical samples were used to compare (i) the commonly used MgPa assay for the
      detection of M. genitalium infections (MgPa qPCR), (ii) a combined 23S rRNA gene
      PCR/sequencing assay (Mg23S qPCR/Sequencing) to identify macrolide resistance
      associated mutations, and (iii) our newly developed probe-based melt curve qPCR
      for simultaneous detection of M. genitalium and macrolide resistance-associated
      mutations (Macrolide-R/MG ELITe MGB Kit, Elitech Bothel USA in short Mg
      MacrolideR qPCR). Specificity of the qPCR was tested using urogenital samples
      that were tested positive for a range of other micro-organisms. M. genitalium was
      detected in 196/236 (83.1%) samples by the MgPa qPCR, versus 172/236 (72.9%) by
      the combined Mg23S qPCR/Sequencing, and 202/236 (85.6%) by the Mg MacrolideR
      qPCR. The Mg MacrolideR qPCR showed high concordance to the Mg23S qPCR/Sequencing
      assay (201 vs 202 could be genotyped, respectively) for the detection of the
      macrolide resistant mutations. None of the other urogenital pathogens were tested
      positive in the Mg MacrolideR qPCR, indicating specificity. The Mg MacrolideR
      qPCR is fast, sensitive, specific, and can easily be implemented in the routine
      diagnostics.

PMID- 30276586
TI  - Structure, electronic properties, and NBO and TD-DFT analyses of nickel(II),
      zinc(II), and palladium(II) complexes based on Schiff-base ligands.
AB  - In this work we studied the structural and electronic properties of the metal
      Schiff base complexes Ni[Formula: see text] (1), Pd[Formula: see text] (2),
      Zn[Formula: see text] (3), and Ni[Formula: see text](4), where L1 and L2 are
      Schiff bases synthesized from salicylaldehyde and 2-hydroxy-5-methylbenzaldehyde,
      respectively. Natural bond analysis showed that in complexes 1 and 2, the metal
      ion coordinates to the ligands through electron donation from lone pairs on
      ligand nitrogen and oxygen atoms to s and d orbitals on the metal ion. In complex
      3, metal-N and metal-O bonds are formed through charge transfer from the lone
      pairs on nitrogen and oxygen atoms to an s orbital of Zn. Dimethylation of the
      phenolate rings in the ligands decreases the energy gap and redshifts the
      spectrum of the nickel complex. The main absorptions observed were assigned on
      the basis of singlet-state transitions. The simulated spectra of the two
      complexes 1 and 2 are characterized by excited states with ligand-to-ligand
      charge-transfer (LLCT), metal-to-ligand charge-transfer (MLCT), ligand-to-metal
      charge-transfer (LMCT), and metal-centered (MC) character. Graphical abstract
      Geometric structure of the palladium complex.

PMID- 30276587
TI  - Geochemical characterization and renal cell toxicity of water-soluble extracts
      from U.S. Gulf Coast lignite.
AB  - An assortment of organic material can leach from lignite (low-rank coal) in
      water, and the water-soluble fraction from lignite has been associated with
      adverse health effects in areas of the Balkans. Recent efforts have been made to
      evaluate this hypothesis in other areas where lignite is in contact with
      groundwater like in the U.S. Gulf Coast region. In this study, five Gulf Coast
      lignite samples were extracted with water, and the water-soluble portion of the
      coal was then characterized by total organic carbon, UV-Vis spectroscopy, and gas
      chromatography/mass spectrometry. Additionally, human kidney cells (HK-2) were
      exposed to water-soluble extracts of Gulf Coast lignite to assess toxicity. Cell
      viability was measured, and a dose-response curve was used to generate IC50
      values that ranged from 490 to 3000 ppm. The most toxic extract (Dolet Hills) was
      from Louisiana where lignite-derived organic material has been previously linked
      to high incidence of renal pelvic cancer. Concentrations of nephrotoxic metals
      (As, Cd, Co, Cu, Hg, Pb, V, Zn) were screened and were below those considered
      toxic to renal cells. We conclude that leachates from lignite do indeed have
      toxic affects on cultured human renal cells. Although the IC50 values are higher
      than the concentration of organic matter in the local groundwater, typically < 5
      ppm, the effects of long-term low-level exposure is not known.

PMID- 30276589
TI  - Letter to the Editor: Mesenteric Lymphatic Vessel Density Is Associated with
      Disease Behavior and Postoperative Recurrence in Crohn's Disease.

PMID- 30276590
TI  - Lessons from Trauma Care: Abdominal Compartment Syndrome and Damage Control
      Laparotomy in the Patient with Gastrointestinal Disease.

PMID- 30276588
TI  - The Prognostic Impact of KRAS Mutation in Patients Having Curative Resection of
      Synchronous Colorectal Liver Metastases.
AB  - BACKGROUND: m-KRAS has been recently reported to be a significant prognostic
      factor in patients undergoing resection of colorectal liver metastases. This is
      due to the lack of response to monoclonal epithelial growth factor receptor
      antibodies, and potentially as a result of a more aggressive tumor biology.
      METHODS: The National Cancer Database was queried to identify patients with known
      KRAS status presenting with colorectal cancer and liver metastases who underwent
      resection of the primary tumor and metastatic disease between 2010 and 2015.
      RESULTS: A total of 2655 patients were identified of which 1116 (42%) had m-KRAS.
      Tumor size, lymph node involvement rates, and margin status of the primary tumor
      were similar between patients with m-KRAS and wild-type KRAS (wt-KRAS). In the
      multivariable analysis, African-American race and right-sided colon cancers were
      independently associated with m-KRAS (both p < 0.001). m-KRAS patients had a
      significantly lower overall survival (OS) than those with wt-KRAS, with a 3- and
      5-year OS of 51 vs. 64% and 31 vs. 42%, respectively (p < 0.001). After
      adjustment for available prognostic confounders, factors independently associated
      with worse OS were increasing age, receipt of monoagent chemotherapy, tumor size,
      positive lymph node, and resection margin status of the primary tumor, right
      sided cancers, and m-KRAS. CONCLUSIONS: m-KRAS is associated with worse OS in
      patients presenting with colorectal cancer and liver metastases undergoing
      resection of the primary tumor and metastatic disease. Right-sided lesions and
      African-American race were associated with m-KRAS. However, while right-sided
      remained an independent prognostic factor for OS, race did not.

PMID- 30276585
TI  - The Toll Pathway in the Central Nervous System of Flies and Mammals.
AB  - Toll receptors, first identified to regulate embryogenesis and immune responses
      in the adult fly and subsequently defined as the principal sensors of infection
      in mammals, are increasingly appreciated for their impact on the homeostasis of
      the central as well as the peripheral nervous systems. Whereas in the context of
      immunity, the fly Toll and the mammalian TLR pathways have been researched in
      parallel, the expression pattern and functionality have largely been researched
      disparately. Herein, we provide data on the expression pattern of the Toll
      homologues, signaling components, and downstream effectors in ten different cell
      populations of the adult fly central nervous system (CNS). We have compared the
      expression of the different Toll pathways in the fly to the expression of TLRs in
      the mouse brain and discussed the implications with respect to commonalities,
      differences, and future perspectives.

PMID- 30276591
TI  - Updates in medical professional liability: a primer for electrophysiologists.
AB  - Medical professional liability (MPL), traditionally known as medical malpractice,
      affects most electrophysiologists some point during their career, either directly
      through personal experience or indirectly by the experiences of colleagues.
      Despite this, most physicians struggle to accurately describe MPL in the context
      of clinical practice. Providers know little about the outcomes of malpractice
      claims as reporting of settled or litigated MPL cases is sparse in the medical
      literature. In the USA, individual patients can file a malpractice claim in a
      tort-based system, whereas in other parts of the world, no-fault malpractice
      systems are increasingly prevalent. Tort reform remains a topic of much debate as
      the economic costs of malpractice contribute to the ever-expanding costs of
      health care in the USA. This review provides a framework to define MPL, describes
      the tort and no-fault systems of malpractice, and details the economic impacts of
      MPL on health care and the practice of cardiology in the USA. Current policy
      trends towards MPL including tort reform are reviewed, and MPL as it relates to
      the practice of cardiac electrophysiology is detailed.

PMID- 30276592
TI  - Remote monitoring of subcutaneous implantable cardioverter defibrillators.
AB  - BACKGROUND: Remote monitoring (RM) of implantable cardioverter defibrillators
      (ICD) has been shown to improve patient safety and reduce in-office visits. The
      subcutaneous ICD (S-ICD) is an effective alternative to transvenous ICD and has
      recently been endowed with the RM function. However, the RM communicator for S
      ICD requires patient interaction to activate data transmission. We assessed
      patient compliance and acceptance. METHODS: Patients with S-ICD received the
      communicator and were followed up for 15 months. Weekly remote transmissions were
      programmed. Compliance with checks was measured as the number of checks performed
      by the patient divided by the number of automatic notifications by the
      communicator. A questionnaire on acceptance of the system was administered to
      patients. RESULTS: A total of 106 patients were analyzed. The proportion of
      weekly checks properly executed by the patients was 94% during the first 3 months
      and 93% from months 12 to 15. Of the checks performed, 93% were on the same day
      as the automatic notification. On a patient basis, compliance with weekly checks
      was > 85% (less than one check missed per month) in 88% of patients during the
      first 3 months and in 82% from months 12 to 15 (p = 0.615). No variables emerged
      as predictors of lower (<= 85%) long-term compliance with weekly checks. During
      follow-up, 49 alerts were transmitted and the mean delay between the detected
      event and the patient transmission was 2 +/- 2 days. The majority of patients
      found the system easy to use and felt confident about being remotely monitored.
      CONCLUSIONS: The level of patient compliance with remote checks is high with
      current technology for RM of S-ICD. The vast majority of data transmissions are
      consistently performed on a weekly basis on the day scheduled.

PMID- 30276593
TI  - Maternal cinnamon intake during lactation led to visceral obesity and hepatic
      metabolic dysfunction in the adult male offspring.
AB  - PURPOSE: Studies with foods, known to promote health benefits in addition to the
      nutritive value, show that their consumption by pregnant and/or lactating females
      could induce negative outcomes to the offspring. It is well characterized that
      cinnamon intake promotes benefits to energy homeostasis. The present study aimed
      to analyze the effects of the consumption of an aqueous extract of cinnamon by
      lactating female rats on the endocrine-metabolic outcomes in the adult offspring.
      METHODS: Lactating dams (Wistar rats) were supplemented with cinnamon aqueous
      extract (400 mg/kg body weight/day) for the entire lactating period. The male
      adult offspring were evaluated at 180 days old (CinLac). RESULTS: The offspring
      presented visceral obesity (P = 0.001), hyperleptinemia (P = 0.002), and
      hyperinsulinemia (P = 0.016). In the liver, CinLac exhibited reduced p-IRbeta (P
      = 0.018) suggesting insulin resistance. However, phosphorylation of IRS1 (P =
      0.041) and AKT (P = 0.050) were increased. JAK2 (P = 0.030) and p-STAT3 (P =
      0.015) expressions were higher, suggesting that the activation of IRS1/AKT in the
      CinLac group could have resulted from the increased activation of leptin
      signaling. Although we observed no changes in the gluconeogenic pathway, the
      CinLac group exhibited lower hepatic glycogen content (P = 0.005) accompanied by
      increased p-GSK3beta (P = 0.011). In addition, the CinLac group showed increased
      hepatic triacylglycerol content (P = 0.049) and a mild steatosis (P = 0.001),
      accompanied by reduced PPARalpha mRNA expression (P = 0.005). CONCLUSION: We
      conclude that maternal intake of aqueous extract of cinnamon induces long-term
      molecular, metabolic, and hormonal changes in the adult progeny, including
      visceral obesity, higher lipid accumulation, and lower glycogen content in the
      liver.

PMID- 30276594
TI  - Posterior pituitary tumours: the spectrum of a unique entity. A clinical and
      histological study of a large case series.
AB  - PURPOSE: In 2017, the WHO established that pituicytoma, granular cell tumour
      (GCT) and spindle cell oncocytoma (SCO) are posterior pituitary tumours (PPT).
      Recent data suggests that these tumours probably arise from the pituicytes and
      may constitute a spectrum of a unique histopathological entity. Our aim is to
      report the clinical findings and surgical outcomes of 16 patients with PPT. We
      also evaluated the tissue specimens available in light of current knowledge.
      METHOD: Cross-sectional study with retrospective data. RESULTS: PPT were 7
      pituicytomas, 3 GCT and 6 SCO. Patients mean age was 55 years old and 75% were
      female. Basal hormonal study showed hyperprolactinemia (43.7%) and
      hypopituitarism (37.5%). There was no case of diabetes insipidus (DI). MRI showed
      sellar/suprasellar masses with mean size of 19.7mm. PPT was not suspected in any
      patient. Fifteen patients underwent surgery and complications were common: 20%
      had perioperative bleeding (one patient died because of a massive haemorrhage),
      57.1% hypopituitarism, 35.7% permanent DI and 21.4% underwent a second surgery.
      Pathological findings shown positivity for thyroid transcription factor 1,
      vimentin and negativity for cytokeratin and chromogranin A in all specimens
      evaluated. S100 protein was positive in 88.8% of tumours. Ki67 was >= 3% in 66.6%
      and ranged from 4-7% in SCO. CONCLUSION: PPT have similar histology, clinical
      features and are frequently misdiagnosed as nonfunctioning pituitary tumours.
      However, post-surgical complications including haemorrhage are common. A high
      clinical suspicion is needed to presume the diagnosis prior surgery and diminish
      the high morbidity of these tumours.

PMID- 30276595
TI  - Diagnostic value of ultrasonography and TI-201/Tc-99m dual scintigraphy in
      differentiating between benign and malignant thyroid nodules.
AB  - PURPOSE: To evaluate the performance of ultrasonography (US) and TI-201/Tc-99m
      dual (Tl/Tc) scintigraphy in differentiating between benign and malignant thyroid
      nodules. METHODS: Eighty-six patients diagnosed to have a thyroid tumor on
      postoperative histopathologic examination between June 2009 and February 2017
      were included in this retrospective study. A radiologist reviewed the US and
      Tl/Tc scintigraphy reports along with all available clinical and histopathologic
      information. On Tl/Tc scintigraphy, a nodule in which uptake was higher in the
      delayed phase than in the surrounding parenchyma was defined as a delayed
      accumulation pattern and a nodule in which uptake was higher in the delayed phase
      than in the early phase was defined as a persistent pattern. The Tl/Tc
      scintigraphy images were evaluated in a blinded manner to assess reproducibility.
      A statistical analysis was performed to identify features associated with
      malignancy. Interobserver variability was calculated using the kappa statistic.
      RESULTS: US had higher sensitivity (81.2%), specificity (88.2%), and positive
      (96.6%) and negative (53.6%) predictive values than Tl/Tc scintigraphy. An ill
      defined margin and microcalcification were independent predictors of a malignant
      thyroid nodule on multivariate logistic regression (P = 0.003 and P = 0.014,
      respectively). The persistent pattern had high specificity (85.7%) equivalent to
      that of US but had lower sensitivity (34.7%). The kappa values for the delayed
      accumulation and persistent patterns were 0.66-0.78 and 0.32-0.50, respectively.
      CONCLUSIONS: An ill-defined margin and microcalcification on US were independent
      predictors of a malignant thyroid nodule. A persistent pattern seen on Tl/Tc
      scintigraphy could contribute to the differential diagnosis.

PMID- 30276597
TI  - Minichromosome maintenance complex component 8 and 9 gene expression in the
      menstrual cycle and unexplained primary ovarian insufficiency.
AB  - PURPOSE: DNA repair genes Minichromosome maintenance complex component (MCM) 8
      and 9 have been linked with gonadal development, primary ovarian insufficiency
      (POI), and age at menopause. Our objective was to characterize MCM 8 and 9 gene
      expression in the menstrual cycle, and to compare MCM 8/9 expression in POI vs
      normo-ovulatory women. METHODS: Normo-ovulatory controls (n = 11) and unexplained
      POI subjects (n = 6) were recruited. Controls provided three blood samples within
      one menstrual cycle: (1) early follicular phase, (2) ovulation, and (3) mid
      luteal phase. Six of 11 controls only provided a follicular phase sample.
      Amenorrheic POI subjects provided a single, random blood sample. MCM8/9
      expression in peripheral blood was assessed with qRTPCR. Analyses were performed
      using delta-Ct measurements; group differences were transformed to a fold change
      (FC) and confidence interval (CI). Differences across menstrual cycle phases were
      compared using random effects ANOVA. Two-sample t tests were used to compare two
      groups. RESULTS: MCM8 expression was significantly lower at ovulation and during
      the luteal phase, when compared to the follicular phase [FC = 0.69 in the luteal
      vs follicular phase (p = 0.012, CI = 0.53, 0.90); and 0.65 in the ovulatory vs
      follicular phase (p = 0.0057, CI = 0.50, 0.85)]. No change in MCM9 expression was
      noted throughout the menstrual cycle. No significant difference was seen in
      MCM8/9 expression when comparing POI to control subjects. CONCLUSIONS: Our study
      showed greater MCM8 expression in the follicular phase of the menstrual cycle,
      compared to the ovulatory and luteal phases. No cyclic changes were seen with
      MCM9. Significant differences in MCM8/9 expression were not detected between POI
      and controls; however, we recommend further investigation with a larger sample
      population.

PMID- 30276598
TI  - Persistence Mindset among Adolescents: Who Benefits from the Message that
      Academic Struggles are Normal and Temporary?
AB  - Research proposing that mindset interventions promote student achievement has
      been conducted at a frenetic pace nationwide in the United States, with many
      studies yielding mixed results. The present study explores the hypothesis that
      mindset interventions are beneficial for students only under specific
      circumstances. Using a randomized controlled trial with student-level random
      assignment within two public schools (School 1: n = 198 seventh-graders, 73%
      Black, 27% White, 53% male; School 2: n = 400 ninth-graders, 98% White, 2% Black,
      52% male), this trial conceptually integrated elements from three evidence-based
      mindset interventions. It then examined two theoretically driven moderators of
      student performance following the transition to middle or high school: students'
      racial backgrounds and students' educational expectations. Results indicated that
      the intervention was effective for a particular subset of students-Black students
      with high educational expectations-resulting in higher grades over the course of
      the year. Among students with low educational expectations (regardless of race),
      the intervention did not impact grades. For White students with high educational
      expectations, the control activities actually benefitted grades more than the
      mindset intervention. Both theoretical and practical implications for mindset
      research are discussed.

PMID- 30276599
TI  - The evaluation of prostate lesions with IVIM DWI and MR perfusion parameters at
      3T MRI.
AB  - PURPOSE: The purpose of our study was to analyze the difference between IVIM DWI
      and perfusion parameters of malignant lesions and benign lesions-normal prostate
      tissue. METHODS: This prospective study included 31 patients who had
      multiparametric prostate MRI with IVIM DWI due to elevated prostate-specific
      antigen level and clinical suspicion between February 2015 and September 2016.
      RESULTS: For peripheral zone, the mean values of Ktrans, Kep, iAUC, chi2 and f
      were significantly higher in malignant lesions, and the mean values of Dt were
      significantly lower in malignant lesions (p 0.00, p 0.02, p 0.00, p 0.02 and p
      0.00, respectively). For transitional zone, the mean values of Ktrans, Ve, iAUC,
      chi2 and f were significantly higher in malignant lesions, and the mean values of
      Dp and Dt were significantly lower in malignant lesions (p 0.00, p 0.00, p 0.00,
      p 0.00, p 0.00, p 0.02 and p 0.00, respectively). For whole prostate gland, the
      mean values of Ktrans, Kep, Ve, iAUC, chi2 and f were significantly higher in
      malignant lesions, and the mean values of Dp and Dt were significantly lower in
      malignant lesions (p 0.00, p 0.03, p 0.00, p 0.00, p 0.00, p 0.01, p 0.04 and p
      0.00, respectively). CONCLUSIONS: Restricted diffusion-pseudodiffusion and
      increased perfusion parameters are important to differentiate prostate cancer
      from benign pathologies. It is also important to keep in mind that transitional
      zone and peripheral zone tumors may have different perfusion and diffusion
      parameters. Future studies are needed to confirm our findings.

PMID- 30276600
TI  - Does neutrophyl to lymphocyte ratio really predict chronic kidney disease
      progression?
AB  - PURPOSE: Chronic kidney disease (CKD) is an inflammatory process. In addition to
      increased morbidity and mortality, inflammation also contributes to the
      progression of CKD. Neutrophil/lymphocyte ratio (NLR) is a marker of
      inflammation. Some recent data suggest that NLR may predict the progression of
      CKD. METHODS: In this study, 5-year data of 740 patients with stage 2-4 CKD were
      reviewed retrospectively. Demographic data, NLR, CRP, albumin, the amount of
      proteinuria were recorded. At the beginning and the end of follow-up the
      glomerular filtration rate (GFR) and the annual GFR decline rate were calculated.
      Patients were divided to high and low NLR group according to median value of
      their baseline NLR. Reaching stage 5 CKD or initiation of renal replacement
      therapy was determined as end-point for follow-up. RESULTS: The mean age was 62.8
      +/- 0.57 years, eGFR 40 ml/min/1.73 m2, median NLR was 2.76. NLR increased as the
      CKD-stage increased. Mean follow-up time was 51.2 +/- 30 months and 21.4% of
      patients reached the end-point. NLR was significantly increased at follow-up
      (from 3.22 to 5.68, p < 0.001). Annual GFR loss and baseline CRP were higher but
      baseline albumin and GFR were lower of patients with high NLR. The percent of
      patients reaching the end-point was not different between the groups with high
      and low baseline NLR. Kaplan Meier analysis showed that patients with high NLR
      had significantly lower mean renal survival (86.5 months) than patients with low
      NLR (105 months) (p < 0.001). In the Cox-regression analysis NLR was not an
      independent predictor in reaching the end-point but presence of diabetes
      mellitus, younger age and low baseline eGFR were found effective. CONCLUSIONS:
      NLR is an indicator of inflammation in chronic kidney disease. It may not be an
      independent predictor of CKD progression except that the CKD is in a more
      advanced stage and reflects the associated inflammation. Classical risk factors
      such as DM and lower GFR are more powerful predictors of progression.

PMID- 30276602
TI  - Outcomes of laparoscopic resection of urachal remnants followed by novel
      umbilicoplasty.
AB  - OBJECTIVE: The purpose of the study was to report the outcomes of our modified
      techniques of laparoscopic urachal resection, followed by novel umbilical-plasty
      using dermal regenerative grafts for symptomatic urachal remnants. METHODS:
      Between March 2014 and December 2016, laparoscopic urachal resection was carried
      out on 45 patients with complaints of urachal remnants. After extraction of the
      specimen and closure of the fascia at the umbilical site, a 1-cm square section
      of dermal regeneration sheet (TERUDERMIS(r), Olympus) was suture retained between
      the fascia and the skin. Patient satisfaction with cosmesis was scored
      prospectively using the visual analogue scale (VAS). Perioperative records were
      reviewed to assess surgical outcomes. RESULTS: Laparoscopic urachal resection was
      successfully conducted via the transperitoneal approach. Postoperative bleeding
      was experienced in one patient (2.2%), which was subsequently controlled
      laparoscopically. Infection subsided with symptomatic relief in all patients. No
      symptomatic recurrences were encountered. Over 80% of patients (37/45) rated the
      cosmetic outcome of the plasty as good to excellent, with the median scores of 8
      (range 5-10). CONCLUSIONS: Laparoscopic urachal resection is safe and curative
      with reasonable risk of complications. Novel umbilicoplasty using dermal
      regenerative graft is very simple technique and offers satisfactory cosmetic
      outcomes. Further follow-up and cosmesis evaluation are required.

PMID- 30276601
TI  - Decreased percentage of memory B cells is independently associated with increased
      susceptibility to infection in patients on maintenance hemodialysis.
AB  - PURPOSE: Infection is a common complication and cause of death in patients on
      maintenance hemodialysis (MHD). B lymphocytes, which are an important component
      of the immune system, play a significant role in defending against pathogen
      invasion. However, in patients on MHD, the connection between infection and B
      cell subsets remains largely unknown. Our study aims to clarify the potential
      role of the distribution of B cell subsets in the infection process in patients
      on MHD. METHODS: In this cross-sectional study, basic information was collected
      from 175 patients on MHD from July 2016 to July 2017 at Zhongshan Hospital, Fudan
      University. The distributions of the B cell subsets in patients with and without
      infection were analyzed using flow cytometry to determine the role of B
      lymphocyte subsets in the infection process in patients on MHD. RESULTS: Among
      the 175 patients, 45 suffered from infection. The respiratory tract was the most
      common infection site, accounting for 67.86% of all infections. After adjustment
      using multivariate logistic regression models, memory B cells [per 1% increase,
      odds ratio [95% confidence interval (CI)]: 0.949 (0.915, 0.984), P < 0.01],
      switched memory B cells [per 1% increase, odds ratio (95% CI): 0.939 (0.898,
      0.982), P < 0.01], naive B cells [per 1% increase, odds ratio (95% CI): 1.042
      (1.009, 1.075), P < 0.05] and IgG titers [per 1 g/L increase, odds ratio (95%
      CI): 0.779 (0.630, 0.963), P < 0.05] were independent risk factors for infection
      in dialysis patients. CONCLUSION: A decrease in memory B cells is independently
      associated with an increased risk of infection in patients on dialysis.

PMID- 30276603
TI  - Relation of serum spondin-2 levels with cardiac morphology and inflammatory
      parameters in hemodialysis patients.
AB  - PURPOSE: Cardiovascular diseases are the leading causes of mortality in chronic
      kidney disease. Spondin-2 (SP-2), an intrinsic cardio-protective factor, prevents
      maladaptive remodeling. We aimed to determine the relation between serum SP-2
      levels and cardiac morphology along with inflammatory parameters in hemodialysis
      (HD) patients. METHOD: The study comprised a total of 95 patients (61 females)
      receiving HD treatment three times a week for at least 6 months, and a control
      group consisting of age and gender matched 62 subjects (34 females). SP-2 levels
      were determined by ELISA. Echocardiography, 24-h ambulatory blood pressure
      monitoring, and carotid artery intima-media thickness (CIMT) measurement were
      performed in all subjects. The relation of serum SP-2 levels with CIMT,
      echocardiographic parameters, CRP, and absolute neutrophil-to-lymphocyte count
      ratio (NLR) was evaluated by correlation analysis. RESULTS: SP-2 levels were
      found to be significantly higher in the HD group than the control group (16.660
      [8.719-20.938] vs. 3.988 [2.702-8.042] ng/L; P < 0.001). CIMT, CRP, and NLR were
      also higher in HD group (P < 0.005, P < 0.001, and P < 0.001, respectively).
      Significantly positive correlation was found between SP-2 and left ventricular
      mass, left ventricular mass index, CRP, and NLR, but no correlation was
      determined between SP-2 and CIMT. SP-2 was not statistically significant variable
      for the determination of LVH in univariate logistic regression analysis [Wald =
      2.375; OR (95% CI) = 1.000 (0.999-1.000), P = 0.123]. CONCLUSION: Serum SP-2
      levels were higher in HD patients compared to the population with normal renal
      functions. The results suggest that SP-2, an uremic toxin, might be effective
      over a complex pathway in the inflammatory process and in the pathogenesis of
      cardiovascular diseases of patients under HD treatment.

PMID- 30276605
TI  - Stable nuclear transformation of rhodophyte species Porphyridium purpureum:
      advanced molecular tools and an optimized method.
AB  - A mutated phytoene desaturase (pds) gene, pds-L504R, conferring resistance to the
      herbicide norflurazon has been reported as a dominant selectable marker for the
      genetic engineering of microalgae (Steinbrenner and Sandmann in Appl Environ
      Microbiol 72:7477-7484, 2006; Prasad et al. in Appl Microbiol Biotechnol
      98(20):8629-8639, 2014). However, this mutated genomic clone harbors several
      introns and the entire expression cassette including its native promoter and
      terminator has a length > 5.6 kb, making it unsuitable as a standard selection
      marker. Therefore, we designed a synthetic, short pds gene (syn-pds-int) by
      removing introns and unwanted internal restriction sites, adding suitable
      restriction sites for cloning purposes, and introduced the first intron from the
      Chlamydomonas reinhardtii RbcS2 gene close to the 5'end without changing the
      amino acid sequence. The syn-pds-int gene (1872 bp) was cloned into pCAMBIA 1380
      under the control of a short sequence (615 bp) of the promoter of pds (pCAMBIA
      1380-syn-pds-int). This vector and the plasmid pCAMBIA1380-pds-L504R hosting the
      mutated genomic pds were used for transformation studies. To broaden the existing
      transformation portfolio, the rhodophyte Porphyridium purpureum was targeted.
      Agrobacterium-mediated transformation of P. purpureum with both the forms of pds
      gene, pds-L504R or syn-pds-int, yielded norflurazon-resistant (NR) cells. This is
      the first report of a successful nuclear transformation of P. purpureum.
      Transformation efficiency and lethal norflurazon dosage were determined to
      evaluate the usefulness of syn-pds-int gene and functionality of the short
      promoter of pds. PCR and Southern blot analysis confirmed transgene integration
      into the microalga. Both forms of pds gene expressed efficiently as evidenced by
      the stability, tolerance and the qRT-PCR analysis. The molecular toolkits and
      transformation method presented here could be used to genetically engineer P.
      purpureum for fundamental studies as well as for the production of high-value
      added compounds.

PMID- 30276604
TI  - Serum endocan and circadian heart rate variability in non-dialysis stage 5
      chronic kidney disease patients.
AB  - BACKGROUND: Chronic kidney disease (CKD) is very common now and is associated
      with high overall and cardiovascular mortality. Numerous studies have reported
      that elevated heart rate (HR) is a risk factor for cardiovascular mortality. We
      investigated the link between serum endocan and circadian heart rate variability
      in non-dialysis stage 5 CKD patients. METHODS: In a cross-sectional study, we
      enrolled 54 prevalent n non-dialysis stage 5 CKD patients (32 males, aged 48.2 +/
      14.92 years). HR was measured with an automatic system. Serum endocan level was
      analyzed by ELISA. RESULTS: Night/day HR ratio was independently predicted by
      serum endocan level (P < 0.01) and hypertension history (P < 0.05). Adjusted R2
      of the model was 0.222. CONCLUSION: Increased serum endocan is significantly
      associated with circadian heart rate variability in non-dialysis stage 5 CKD
      patients. Further investigation is needed to explore the potential benefits of
      serum endocan lowering therapy in this patient group.

PMID- 30276606
TI  - Distally based anterolateral thigh flap: an underutilized option for peri
      patellar wound coverage.
AB  - Wound coverage in the supra-patellar area presents a significant challenge for
      orthopaedic and reconstructive surgeons due to the need for preservation of knee
      joint function but the paucity of regional soft tissue flaps available. While
      many orthopaedic and reconstructive surgeons make use of the rotational
      gastrocnemius flap for coverage of peri-patellar defects, this flap has certain
      limitations. The goal of this study was to report a single-centre experience with
      the use of the distally based anterolateral thigh flap (ALT) and review the
      current literature on the use of the ALT for peri-patellar defects. In this
      report, both a single-centre experience using distally based anterolateral thigh
      (ALT) island flaps for supra-patellar wound coverage and the existing literature
      on this topic were reviewed. A systematic literature review was performed to
      assess the use of the ALT for peri-patellar wounds. Five patients with a mean age
      of 69 underwent a distally based ALT flap for coverage of peri-patellar defects.
      Four out of 5 flaps survived at the end of their respective follow-up. Based on
      this combined experience, the distally based reverse-flow anterolateral thigh
      island flap represents a useful but relatively underutilized option for
      appropriately selected supra-patellar wounds due to minimal donor site morbidity,
      multiple flap components, and predictable pedicle anatomy. The flap's major
      weakness is its potentially unreliable venous drainage, requiring delay or
      secondary venous outflow anastomosis. Given the ALT flap's favourable profile,
      the authors recommend consideration for its use when managing a peri-patellar
      coverage wound issue.

PMID- 30276609
TI  - Search efficiency is not sufficient: The nature of search modulates stimulus
      driven attention.
AB  - It has long been debated whether or not a salient stimulus automatically attracts
      people's attention in visual search. Recent findings showed that a salient
      stimulus is likely to capture attention especially when the search process was
      inefficient due to high levels of competition between the target and distractors.
      Expanding these studies, the present study proposes that a specific nature of
      visual search, as well as search efficiency, determines whether or not a salient,
      task-irrelevant singleton stimulus captures attention. To test this proposition,
      we conducted three experiments, in which participants performed two visual search
      tasks whose underlying mechanisms are known to be different: orientation-feature
      search and Landolt-C search tasks. We found that color singleton distractors
      captured attention when participants performed the orientation-feature search
      task. The magnitude of this capture effect increased as search efficiency
      decreased. On the contrary, the capture by singleton distractors was not observed
      under the Landolt-C search task. This differential pattern of capture effect was
      not due to differences in search efficiency across the search tasks; even when
      search efficiency was controlled for, stimulus-driven capture of attention by a
      salient distractor was found only under the feature search. Based on these
      results, the present study suggests that in addition to search efficiency, the
      nature of search strategy and the extent to which attentional control is strained
      play crucial roles in observing stimulus-driven attentional capture in visual
      search.

PMID- 30276608
TI  - CXCR5 overexpression in HL-60 cells enhances chemotaxis toward CXCL13 without
      anticipated interaction partners or enhanced MAPK signaling.
AB  - CXCR5 is a serpentine receptor implicated in cell migration in lymphocytes and
      differentiation in leukocytes. It causes MAPK pathway activation and has known
      membrane partners for signaling. CXCR5 mRNA is reportedly expressed in
      neutrophils following isolation, but its role in this cellular context is
      unknown. CXCR5 is also expressed in HL-60 cells, a human acute myeloid leukemia
      line, following treatment with all-trans retinoic acid, which induces
      differentiation toward a neutrophil-like state. CXCR5 is necessary for this
      process; differentiation was crippled in CXCR5 knockout cells and enhanced in
      cells ectopically expressing it. Since CXCR5 has various membrane protein
      partners, we investigated whether CXCR5-driven all-trans retinoic acid-induced
      differentiation depends on its association with such partners. Pursuing this, we
      generated HL-60 cells overexpressing the protein. We found that CXCR5 drove
      migration toward its ligand, CXCL13, and probed for interactions with several
      candidates using flow cytometry-based Forster resonance energy transfer.
      Surprisingly, we did not detect interactions with any candidates, including three
      reported in other cellular contexts. Additionally, we observed no significant
      changes in all-trans retinoic acid-induced differentiation; this may be due to
      the stoichiometry of CXCR5 and partner receptors or CXCL13. The anticipated
      membrane partnerings were surprisingly apparently unnecessary for downstream
      CXCR5 signaling and all-trans retinoic acid-induced differentiation.

PMID- 30276607
TI  - A methyl 1H double quantum CPMG experiment to study protein conformational
      exchange.
AB  - Protein conformational changes play crucial roles in enabling function. The Carr
      Purcell-Meiboom-Gill (CPMG) experiment forms the basis for studying such dynamics
      when they involve the interconversion between highly populated and sparsely
      formed states, the latter having lifetimes ranging from ~ 0.5 to ~ 5 ms. Among
      the suite of experiments that have been developed are those that exploit methyl
      group probes by recording methyl 1H single quantum (Tugarinov and Kay in J Am
      Chem Soc 129:9514-9521, 2007) and triple quantum (Yuwen et al. in Angew Chem Int
      Ed Engl 55:11490-11494, 2016) relaxation dispersion profiles. Here we build upon
      these by developing a third experiment in which methyl 1H double quantum
      coherences evolve during a CPMG relaxation element. By fitting single, double,
      and triple quantum datasets, akin to recording the single quantum dataset at
      static magnetic fields of Bo, 2Bo and 3Bo, we show that accurate exchange values
      can be obtained even in cases where exchange rates exceed 10,000 s-1. The utility
      of the double quantum experiment is demonstrated with a pair of cavity mutants of
      T4 lysozyme (T4L) with ground and excited states interchanged and with exchange
      rates differing by fourfold (~ 900 s-1 and ~ 3600 s-1), as well as with a fast
      folding domain where the unfolded state lifetime is ~ 80 us.

PMID- 30276610
TI  - Fluorescence Quantum Yield Determination of Propylparaben Using Flow Injection
      Spectroscopy.
AB  - The determination of the fluorescence quantum yield of Propylparaben is
      introduced and applied to L-tyrosine as a standard by a new approach that can be
      applied to the pharmaceutical compound utilised in this study. The quantum yield
      is a critical figure of quality for the optical nature of a fluorophore. Numerous
      investigations have considered the glitter in both pharmaceutical and nature
      compounds for its medical and industrial significance. A straightforward method
      is detailed here to decide the quantum yield of Propylparaben in solution as an
      element of the fluorescence concentration. For this reason, L-Tyrosine is chosen
      as a fluorescence standard perspective to gauge the Propylparaben fluorescence
      quantum yield. The impacts of pH, solvents and flow rate on the assessment of
      quantum yield and quantum efficiency, for the reference and the solutions of
      Propylparaben, have been investigated. The results indicated that these
      parameters significantly influence the accuracy of the method. Diverse methods
      are concentrated on to represent distinctive quantum yield advancements with the
      quantum efficiency. The impact of these parameters was likewise considered. In
      this study, the application of the single method may be taken into consideration
      to compute quantum yield of Propylparaben, which was 0.36, and this is an
      exceptionally basic and general technique to solve the imperative issue of
      luminescence quantum yield assurance of other fluorescence compounds.

PMID- 30276611
TI  - Photophysical and Electrochemical Studies of 4-Dicyanomethylene 2,6-Dimethyl-4H
      Pyran (DDP) Dye with Amides in Water.
AB  - Photophysical and electrochemical studies of DDP dye with Formamide and alkyl
      substituted amides were carried out in water. Addition of Formamide (F),
      Acetamide (ACM), N,N-Dimethylformamide (DMF), Dimethylacetamide (DMAC) to DDP dye
      result in an isosbestic point. A fluorescence enhancement of DDP dye is observed
      on the addition of amides. Apart from the fluorescence enhancement, the addition
      of formamide result in no significant shift in the position of emission maxima of
      DDP dye whereas addition of ACM and DMF result in a shift towards the blue and
      red region respectively. DDP dye exhibits three lifetime components which are
      unique in lifetime and amplitude. The fluorescence lifetime and relative
      amplitude of DDP dye varies significantly by addition of amides in aqueous
      solution which are influenced by amidewater hydrogen-bonding network and
      hydrophobic influences of the alkyl substituted amides. The nature of interaction
      between dye and amide be predominantly through hydrogen-bonding wherein the
      carbonyl oxygen (C=O) of amides are bonded to N-H hydrogen of DDP dye through
      water molecule. The existence of more than one microenvironment of DDP dye in
      aqueous phase is elucidated by Electrochemical Impedence Spectroscopy (EIS)
      through Nyquist plots wherein it signifies that there exist at least three
      different micro environments which support the existence of different
      fluorescence lifetimes. Fluorescence spectral technique is used as an efficient
      tool to elucidate the nature of interaction of water soluble probe with hydrogen
      bonding solutes is established in our studies.

PMID- 30276613
TI  - A Rare Case of Paradoxical Embolization During Thrombolysis for Pulmonary
      Embolus.

PMID- 30276614
TI  - Association Between Therapeutic Hypothermia and Outcomes in Patients with Non
      shockable Out-of-Hospital Cardiac Arrest Developed After Emergency Medical
      Service Arrival (SOS-KANTO 2012 Analysis Report).
AB  - BACKGROUND/OBJECTIVE: The outcomes of patients with non-shockable out-of-hospital
      cardiac arrest (non-shockable OHCA) are poorer than those of patients with
      shockable out-of-hospital cardiac arrest (shockable OHCA). In this retrospective
      study, we selected patients from the SOS-KANTO 2012 study with non-shockable OHCA
      that developed after emergency medical service (EMS) arrival and analyzed the
      effect of therapeutic hypothermia (TH) on non-shockable OHCA patients. METHODS:
      Of 16,452 patients who have definitive data on the 3-month outcome in the SOS
      KANTO 2012 study, we selected 241 patients who met the following criteria: age >=
      18 years, normal spontaneous respiration or palpable pulse upon emergency medical
      services arrival, no ventricular fibrillation or pulseless ventricular
      tachycardia before hospital arrival, and achievement of spontaneous circulation
      without cardiopulmonary bypass. Patients were divided into two groups based on
      the presence or absence of TH and were analyzed. RESULTS: Of the 241 patients, 49
      underwent TH. Univariate analysis showed that the 1-/3-month survival rates and
      favorable 3-month cerebral function outcome rates in the TH group were
      significantly better than the non-TH group (46% vs 19%, respectively, P < 0.001,
      35% vs 12%, respectively, P < 0.001, 20% vs 7%, respectively, P = 0.01).
      Multivariate logistic regression analysis showed that TH was a significant,
      independent prognostic factor for cerebral function outcome. CONCLUSIONS: In this
      study, TH was an independent prognostic factor for the 3-month cerebral function
      outcome. Even in patients with non-shockable OHCA, TH may improve outcome if the
      interval from the onset of cardiopulmonary arrest is relatively short, and
      adequate cardiopulmonary resuscitation is initiated immediately after onset.

PMID- 30276615
TI  - Venous Thromboembolism Prophylaxis in Neurocritical Care Patients: Are Current
      Practices, Best Practices?
AB  - BACKGROUND/OBJECTIVES: Venous thromboembolism (VTE) is a leading cause of
      preventable, in-hospital deaths; critically ill patients have a higher risk.
      Effective and efficient strategies to prevent VTE exist; however, neurocritical
      care patients present unique challenges due to competing risk of bleeding. The
      objective of this study was to examine current VTE prophylaxis practices among
      neurocritical care patients, concordance with guideline-recommended care, and the
      association with clinical outcomes. METHODS: This retrospective cohort study of
      patients admitted to ten adult, medical-surgical and neurological intensive care
      units (ICUs) in nine hospitals between 2014 and 2017 using administrative and
      clinical data. Neurocritical care patients were classified based on the primary
      admission diagnosis. Concordance with guideline-recommended care was evaluated
      using recommendations from recent guidelines. RESULTS: 20.0% of 23,191 patients
      were classified as neurocritical care. Among neurocritical care patients,
      pharmacological VTE prophylaxis was administered on 60.9% of all ICU days,
      mechanical VTE prophylaxis on 46.9%, and no VTE prophylaxis on 12.2% of all ICU
      days. Type of VTE prophylaxis was associated with sex, neurological diagnosis,
      and invasive neurological monitoring. Fifty-six percentage of ICU days were
      guideline concordant but concordance varied by recommendation (range 6-100%) and
      by type of VTE prophylaxis recommended (p = 0.05); among patients where
      guidelines recommended use of pharmacologic prophylaxis, care was concordant
      26.6% of ICU days, whereas for mechanical prophylaxis it was concordant 80.5% of
      ICU days. There was an overall improvement in guideline concordance on 2.3% of
      ICU days after the publication of the Society of Neurocritical Care guideline (p
      = 0.005). CONCLUSIONS: Neurocritical care patients commonly receive mechanical
      VTE prophylaxis despite guidelines recommending the use of pharmacological VTE
      prophylaxis. Our findings suggest uncertainty around best VTE prophylaxis
      practices for neurocritical care patients remains.

PMID- 30276612
TI  - Immune Cells After Ischemic Stroke Onset: Roles, Migration, and Target
      Intervention.
AB  - Ischemic stroke is one of the leading health issues and the major cause of
      permanent disability in adults worldwide. Energy depletion and hypoxia occurring
      after ischemic stroke result in cell death, which activates resident glia cells
      and promotes the peripheral immune cells breaching into brain performing various
      functions even contradictory effects. The infiltration of immune cells may
      mediate neuron apoptosis and escalate ischemic damage, while it enhances neuron
      repair, differentiation, and neuroregeneration. The central nervous system (CNS)
      is immune-privileged site as it is separated from the peripheral immune system by
      the blood-brain barrier (BBB). Pathologically, the diapedesis of peripheral
      immune cells to CNS is controlled by BBB and regulated by immune
      cells/endothelial interactions. As immune responses play a key role in modulating
      the progression of ischemic injury development, understanding the characteristics
      and the contribution on regulating inflammatory responses of glia cells and
      peripheral immune cells may provide novel approaches for potential therapies.
      This review summarizes the multistep process of periphery immune cell
      extravasation into brain parenchyma during immunosurveillance and chronic
      inflammation after ischemic stroke onset. Furthermore, the review highlights
      promising target intervention, which may promote the development of future
      therapeutics for ischemic stroke.

PMID- 30276616
TI  - Motivational deficits in schizophrenia relate to abnormalities in cortical
      learning rate signals.
AB  - Individuals from across the psychosis spectrum display impairments in
      reinforcement learning. In some individuals, these deficits may result from
      aberrations in reward prediction error (RPE) signaling, conveyed by dopaminergic
      projections to the ventral striatum (VS). However, there is mounting evidence
      that VS RPE signals are relatively intact in medicated people with schizophrenia
      (PSZ). We hypothesized that, in PSZ, reinforcement learning deficits often are
      not related to RPE signaling per se but rather their impact on learning and
      behavior (i.e., learning rate modulation), due to dysfunction in anterior
      cingulate and dorsomedial prefrontal cortex (dmPFC). Twenty-six PSZ and 23
      healthy volunteers completed a probabilistic reinforcement learning paradigm with
      occasional, sudden, shifts in contingencies. Using computational modeling, we
      found evidence of an impairment in trial-wise learning rate modulation (alpha) in
      PSZ before and after a reinforcement contingency shift, expressed most in PSZ
      with more severe motivational deficits. In a subsample of 22 PSZ and 22 healthy
      volunteers, we found little evidence for between-group differences in VS RPE and
      dmPFC learning rate signals, as measured with fMRI. However, a follow-up
      psychophysiological interaction analysis revealed decreased dmPFC-VS connectivity
      concurrent with learning rate modulation, most prominently in individuals with
      the most severe motivational deficits. These findings point to an impairment in
      learning rate modulation in PSZ, leading to a reduced ability to adjust task
      behavior in response to unexpected outcomes. At the level of the brain, learning
      rate modulation deficits may be associated with decreased involvement of the
      dmPFC within a greater RL network.

PMID- 30276617
TI  - Transplantation of Cardiac Mesenchymal Stem Cell-Derived Exosomes for
      Angiogenesis.
AB  - We demonstrated the effects of exosomes secreted by cardiac mesenchymal stem
      cells (C-MSC-Exo) in protecting acute ischemic myocardium from reperfusion
      injury. To investigate the effect of exosomes from C-MSC on angiogenesis, we
      injected C-MSC-Exo or PBS intramuscularly into ischemic hind limb. Blood
      perfusion of limb was evaluated by laser Doppler Imaging. We observed that
      ischemic limb treated with C-MSC-Exo exhibits improved blood perfusion compared
      to ischemic limb treated with PBS at 2 weeks and 1 month after induction of limb
      ischemia. To explore the potential mechanisms underlying C-MSC-Exo's angiogenetic
      effect, we performed microRNA array analysis and identify mmu-miR-7116-5p as the
      most abundant enriched miRNA detected in C-MSC-Exo. Bioinformatics' analysis
      shows that miR-7116-5p negatively regulates protein polyubiquitination. In
      conclusion, our study demonstrated that intramuscular delivery of C-MSC-Exo after
      limb ischemia improves blood perfusion, and we identified the most abundant
      miRNAs that are preferentially enriched in C-MSC-Exo.

PMID- 30276618
TI  - Impact of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio on 5
      Year Clinical Outcomes of Patients with Stable Coronary Artery Disease Undergoing
      Elective Percutaneous Coronary Intervention.
AB  - The prognostic role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to
      lymphocyte ratio (PLR) in patients with stable coronary artery disease (CAD) is
      still unclear. We enrolled 500 patients undergoing elective percutaneous coronary
      intervention (PCI). Blood samples were drawn prior to PCI for NLR and PLR
      calculation. Major adverse clinical events (MACE), which included death,
      myocardial infarction (MI), and target vessel revascularization (TVR), were
      recorded up to 5 years. Patients in the higher tertile of NLR presented higher
      Kaplan-Meier estimates of MACE (26.0% vs. 16.9% in tertile 2 vs. 14.3% in tertile
      1; p = 0.042) and death (12.0% vs 6.9% in tertile 2 vs. 4.6% in tertile 1; p =
      0.040), whereas there were no significant differences in the estimates of MI and
      TVR. NLR in the higher tertile was an independent predictor of MACE (HR 1.65, 95%
      CI 1.07-2.55, p = 0.024). No significant difference was observed across tertiles
      of PLR. Unlike PLR, elevated pre-procedural NLR is associated with an increased
      risk of 5-year clinical adverse events.

PMID- 30276619
TI  - A review of the diversity in taxonomy, definitions, scope, and roles in forensic
      medicine: implications for evidence-based practice.
AB  - The scope, roles, and tasks of forensic medicine and forensic medical experts
      currently vary widely between countries and legal systems, which has resulted in
      barriers to organization, standard setting, and quality assurance for practice in
      forensic medicine, including for reporting. The legal fact finder is thus
      confronted with variability in the quality, structure, and content of forensic
      medical reports. We sought to define and categorize the scope, methods, and
      practices that fall under the description of forensic medicine, the various
      issues encountered in current forensic medical practice, and the potential role
      of evidence-based practice in forensic medicine. We searched electronic databases
      and reviewed relevant articles, as well as conducting personal correspondences
      with forensic medical practitioners around the world, to obtain a description of
      current forensic medical practice. The terms forensic medicine, legal medicine,
      medical jurisprudence, medico-legal services, forensic pathology, and clinical
      forensic medicine are used with mixed interpretations in different countries. The
      systems and services rendered are not uniform either. The methods used by
      forensic medical practitioners are not always evidence-based, or based on
      standardized methods, and vary greatly between experts and centers. There are
      also no universally accepted guidelines to prepare a standard and admissible
      report. The lack of a uniform system in forensic medicine creates difficulties in
      assessing the development and performance of forensic medicine as a distinct
      discipline. To prepare evidence-based forensic medical reports, generally
      accepted guidelines are necessary.

PMID- 30276621
TI  - Comment on: Pesticide-Poisoned Patients: Can They Be Used as Potential Organ
      Donors?

PMID- 30276622
TI  - Count-based method for specific binding ratio calculation in [I-123]FP-CIT SPECT
      analysis.
AB  - OBJECTIVE: To calculate the specific binding ratio (SBR) appropriately in
      dopamine transporter (DAT) imaging, a method for extracting the striatal volume
      of interest (VOI) was developed. METHODS: This study included 200 patients (72 +/
      10 years) who were suspected of parkinsonian syndromes (PS) or dementia with
      Lewy body (DLB). The patients were divided into three groups of PS with
      dopaminergic degeneration, DLB and non-PS after [123I]ioflupane (FP-CIT) SPECT
      and clinical follow-up. The image data were reconstructed with CT attenuation
      correction and scatter correction, and with only CT attenuation correction
      (CTAC). The new method extracted striatal VOI according to the high-level counts
      and the average striatum volume, and calculated SBR using the reference occipital
      counts. The SBR values for each patient were obtained using the Tossici-Bolt
      method (SBRBolt) and our method. Reproducibility of SBR calculation using our
      method was compared by two operators. RESULTS: The mean SBR values for the PS and
      DLB groups were significantly different from that of the non-PS group with both
      methods. The coefficients of variation of the SBR were significantly smaller with
      the proposed method compared with those of SBRBolt (p < 0.001), except for the
      CTAC images. There were no differences in SBR between the two operators using our
      method. The diagnostic accuracies with our method for the PS and DLB groups were
      98.4 and 96.0%, respectively. CONCLUSION: Our new method for SBR calculation in
      the FP-CIT SPECT showed less coefficients of variation with high reproducibility,
      which would be useful for clinical diagnosis and in assessing the severity of
      diseases in follow-up studies.

PMID- 30276620
TI  - Correction to: The Toxicology Investigators Consortium Case Registry-The 2017
      Annual Report.
AB  - Please note the Collaborators for this article listed in the Acknowledgements.

PMID- 30276623
TI  - Improvement of left ventricular function after successful radiofrequency catheter
      ablation in persistent atrial fibrillation with preserved left ventricular
      ejection fraction: a comprehensive echocardiographic assessment using two
      dimensional speckle tracking analysis.
AB  - BACKGROUND: A limited number of studies have investigated the effects of
      radiofrequency catheter ablation (RFCA) on left ventricular (LV) function and the
      left atrial (LA) size in patients with atrial fibrillation (AF). The purpose of
      this study was to conduct a comprehensive assessment of LV function in patients
      with AF with preserved left ventricular ejection fraction (LVEF) before and after
      RFCA. METHOD: A total of 30 consecutive patients with no recurrences after RFCA
      for persistent AF (age, 57.7 +/- 8.4 years) were enrolled. Transthoracic
      echocardiography was performed at the baseline and 6 months after the final RFCA
      using speckle tracking derived LV strain analysis. RESULTS: After RFCA, we
      measured decreases in the LA volume index (33.7 +/- 10.4 ml/m2 vs. 24.6 +/- 8.6
      ml/m2, p < 0.0001), while we observed improvements in systolic indices such as
      LVEF (56.8 +/- 9.8% vs. 65.1 +/- 9.1%, p < 0.0001), global longitudinal strain (-
      16.8 +/- 4.4% vs. - 18.8 +/- 3.4%, p = 0.0055) and twist (8.12 +/- 3.66 degrees 
      vs. 12.33 +/- 6.75 degrees , p = 0.0050), and also in diastolic indices such as
      strain rate during early diastole (SRE) (0.73 +/- 0.10 s-1 vs. 1.32 +/- 0.29 s-1,
      p < 0.0001) and early transmitral inflow velocity (E)/SRE (1.11 +/- 0.36 m vs.
      0.61 +/- 0.19 m, p < 0.0001). Logistic regression analysis showed that DeltaE/SRE
      was a contributing factor for improvement in LVEF (odds ratio 126.9; p = 0.021).
      CONCLUSION: In persistent AF with preserved LVEF, further improvement in LVEF and
      reverse remodeling of the LA are achieved after RFCA. LV filling pressure may
      play significant roles in the mechanisms.

PMID- 30276624
TI  - Risk of lung cancer and physical activity by smoking status and body mass index,
      the Norwegian Women and Cancer Study.
AB  - We aimed to investigate physical activity (PA) and risk of different histological
      subtypes of lung cancer according to smoking status and body mass index using
      repeated measurements in a large cohort of women in Norway. The study sample for
      the multiple imputation analyses consisted of 86,499 and for the complete-case
      analysis 80,802 women. Repeated measurements of PA level, smoking habits, weight,
      and height were available for 54,691 women (63.2%), who were included in repeated
      measurement analyses combined with multiple imputation to address attrition. Cox
      proportional hazards regression models were used to calculate hazard ratios with
      95% confidence intervals. During a median follow-up of 12.9 years, 866 cases of
      primary lung cancer were identified. We found an inverse association between PA
      and lung cancer overall. The results were consistent from multiple imputed data
      analysis to complete-case analysis of PA and possible confounders. We observed a
      similar trend for adenocarcinoma, but not for squamous cell or small cell
      carcinomas. Our findings suggest a more pronounced association between lung
      cancer overall and PA levels in current and former smokers, and in normal-weight
      and overweight participants with increasing PA levels. The potential of a
      modifiable lifestyle factor as PA to reduce the risk of lung cancer independently
      of smoking status is important in public health.

PMID- 30276626
TI  - Exploring the Potential of Dendritic Oligoglycerol Detergents for Protein Mass
      Spectrometry.
AB  - The ability to design detergents that are suitable for protein analysis by mass
      spectrometry (MS) represents an on-going challenge in the field of native MS.
      Desirable detergent characteristics include charge-reducing properties and low
      gas-phase stabilities of complexes formed with proteins. In this work, the gas
      phase properties of oligoglycerol detergents (OGDs) are optimized by fine tuning
      of their molecular structure. Furthermore, a tandem mass spectrometry (MS/MS)
      approach is presented that estimates the gas-phase properties of detergents
      simply by studying the dissociation behaviour of protein-detergent complexes
      (PDCs) formed with the soluble protein beta-lactoglobulin (BLG). Graphical
      Abstract ?.

PMID- 30276625
TI  - Conservative Treatment of Hemorrhoids: Results of an Observational Multicenter
      Study.
AB  - INTRODUCTION: This study was conducted to determine the frequency of complaints
      in a cohort of patients with symptomatic hemorrhoidal disease (HD) treated with
      micronized purified flavonoid fraction (MPFF, Detralex). MPFF was selected for
      conservative treatment in this population owing to its proven effects on
      hemorrhoidal symptoms in a large number of patients. METHODS: This multicenter,
      non-interventional study was part of the international CHORUS survey (Chronic
      venous and HemORrhoidal diseases evalUation for improvement of Scientific
      knowledge), conducted in nine centers in different regions of Russia with the
      participation of 80 coloproctologists. The study enrolled consecutive patients
      with complaints of hemorrhoids. All were prescribed MPFF-based conservative
      treatment. The effect of treatment on HD clinical signs and symptoms was assessed
      at two follow-up visits performed 5-7 days and 25-30 days after enrollment.
      Surgical and minimally invasive treatment could be performed from day 7 onwards
      if required. RESULTS: A total of 1952 patients were enrolled. Over the entire
      period of observation, MPFF-based conservative treatment was effective in 1489
      (76.3%) patients in eliminating the main clinical manifestations of disease,
      i.e., bleeding and prolapse of internal nodes. Invasive treatment was performed
      in 68 (3.5%) patients with grade IV hemorrhoids and was combined with MPFF
      conservative treatment in 395 (20.2%) patients with grades I-III hemorrhoids.
      CONCLUSION: Conservative therapy with MPFF was beneficial for relieving
      hemorrhoidal symptoms in the majority of patients. MPFF-based treatment was most
      effective in patients with grade I and II hemorrhoids before irreversible
      degenerative changes in ligaments of the hemorrhoidal plexuses have occurred. It
      was also beneficial in preventing disease relapse in patients with more advanced
      HD and for promoting optimal conditions in the postoperative period. FUNDING:
      Servier.

PMID- 30276627
TI  - Determination of proper treatment time for in vivo blood coagulation and wound
      healing application by non-thermal helium plasma jet.
AB  - The aim of this research was to determine the time of blood coagulation of in
      vivo cuts that treated by the non-thermal atmospheric pressure plasma jet. Also,
      the effect of different treatment times on wound healing has been studied. The
      non-thermal atmospheric pressure plasma jet working in helium gas has been used.
      The averaged treatment time of 8.6 s for in vivo cuts on the Balb/c mouse liver
      showed the complete blood coagulation. Also, the effect of tretament time on
      wound healing has been studied by applying plasma on the wounds for different
      times (10, 20, 30, 40 and 50 s). It was obtained from morphological analysis that
      the treatment groups of 30 s, 40 s and 50 s cause the wounds to be healed faster
      than the groups 10 s and 20 s.The histological analysis showed that in 30 s and
      40 s treatment time groups, the repair process of treated wounds has been
      accelerated, while for 50 s group, it has not been completed, yet. The 30 s
      treatment time has been chosen because of imposing lower dose to living tissue.
      The treated wound area reduction ratios against the control wound reduction
      ratios for 30 s group were obtained 78%, 77% and 63% at the 3rd, 5th and 8th
      days, respectively.

PMID- 30276628
TI  - 1H, 13C, and 15N resonance assignments of N-acetylmuramyl-L-alanine amidase
      (AmiC) N-terminal domain (NTD) from Neisseria gonorrhoeae.
AB  - Gonorrhea infections are becoming more difficult to treat due to the prevalence
      of strains exhibiting resistance to antibiotics and new therapeutic approaches
      are needed. N-acetylmuramyl-L-alanine amidase (AmiC) from Neisseria gonorrhoeae
      is a hydrolase that functions during cell division by cleaving the bond between
      the N-acetylmuramyl and L-alanine moieties of peptidoglycan. Inhibiting this
      enzyme offers the prospect of restoring the efficacy of existing antibiotics as
      treatments against N. gonorrhoeae. Of its two domains, the C-terminal domain
      catalyses the hydrolysis reaction and the N-terminal domain (NTD) is believed to
      target AmiC to its peptidoglycan substrate. Here, we report the 1H, 13C, and 15N
      resonance assignments of a 131 amino acid NTD construct of AmiC by heteronuclear
      NMR spectroscopy. The assignments represent the first for N. gonorrhoeae AmiC
      NTD, laying the groundwork for detailed examination of its structure and
      dynamics, and providing a platform for new drug discovery efforts to address
      antimicrobial-resistant N. gonorrhoeae.

PMID- 30276629
TI  - Best practices: Two Web-browser-based methods for stimulus presentation in
      behavioral experiments with high-resolution timing requirements.
AB  - The Web is a prominent platform for behavioral experiments, for many reasons
      (relative simplicity, ubiquity, and accessibility, among others). Over the last
      few years, many behavioral and social scientists have conducted Internet-based
      experiments using standard web technologies, both in native JavaScript and using
      research-oriented frameworks. At the same time, vendors of widely used web
      browsers have been working hard to improve the performance of their software.
      However, the goals of browser vendors do not always coincide with behavioral
      researchers' needs. Whereas vendors want high-performance browsers to respond
      almost instantly and to trade off accuracy for speed, researchers have the
      opposite trade-off goal, wanting their browser-based experiments to exactly match
      the experimental design and procedure. In this article, we review and test some
      of the best practices suggested by web-browser vendors, based on the features
      provided by new web standards, in order to optimize animations for browser-based
      behavioral experiments with high-resolution timing requirements. Using
      specialized hardware, we conducted four studies to determine the accuracy and
      precision of two different methods. The results using CSS animations in web
      browsers (Method 1) with GPU acceleration turned off showed biases that depend on
      the combination of browser and operating system. The results of tests on the
      latest versions of GPU-accelerated web browsers showed no frame loss in CSS
      animations. The same happened in many, but not all, of the tests conducted using
      requestAnimationFrame (Method 2) instead of CSS animations. Unbeknownst to many
      researchers, vendors of web browsers implement complex technologies that result
      in reduced quality of timing. Therefore, behavioral researchers interested in
      timing-dependent procedures should be cautious when developing browser-based
      experiments and should test the accuracy and precision of the whole experimental
      setup (web application, web browser, operating system, and hardware).

PMID- 30276630
TI  - Potential Direct Costs of Adverse Drug Events and Possible Cost Savings
      Achievable by their Prevention in Tuscany, Italy: A Model-Based Analysis.
AB  - INTRODUCTION: Adverse drug events (ADEs) may represent an important item of
      expenditure for healthcare systems and their prevention could be associated with
      a relevant cost saving. OBJECTIVE: The objective of this study was to simulate
      the annual economic burden for ADEs in Tuscany (Italy) and the potential cost
      savings related to avoidable ADEs. METHODS: A systematic review was performed,
      according to the Preferred Reporting Items for Systematic review and Meta
      Analysis (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology
      (MOOSE) statements, on observational studies published from 2006 to 2016 in
      MEDLINE and EMBASE, focusing on direct costs of ADEs in the inpatient setting
      from high-income countries. The mean probability of preventable ADEs was
      estimated over the included studies. The mean ADE cost was calculated by means of
      Monte Carlo simulation. We then extrapolated the spontaneous reports of ADEs in
      Tuscany, Italy in 2016 from the Italian National Pharmacovigilance Network (Rete
      Nazionale di Farmacovigilanza), and we assumed the same costs and preventability
      probability for these as obtained in the systematic review. Finally, we simulated
      the possible costs of ADEs and preventable ADEs in Tuscany. Three sensitivity
      analyses were also performed to test the robustness of the results. RESULTS: Of
      11,936 articles initially selected, 12 observational studies were included. The
      estimated mean [+/- standard deviation (SD)] ADE cost was ?2471.46 (+/-
      ?1214.13). The mean (+/- SD) probability of preventable ADEs was 45% (+/- 21).
      The Tuscan expenditure for ADEs was ?3,406,280.63 per million inhabitants (95%
      confidence interval (CI) 1,732,910.44-5,079,664.61) and the potential cost saving
      was ?1,532,760.25 per million inhabitants (95% CI 779,776.1-2,285,750.60).
      Sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: The
      present simulation showed that ADEs could have a relevant economic impact on the
      Tuscan healthcare system. In this setting, the prevention of ADEs would result in
      important cost savings. These results could be likely extended to other
      healthcare systems.

PMID- 30276631
TI  - Fall-risk increasing drugs and prevalence of polypharmacy in older patients
      discharged from an Orthogeriatric Unit after a hip fracture.
AB  - BACKGROUND: Polypharmacy and fall-risk increasing drugs (FRIDS) have been
      associated with injurious falls. We aimed to estimate the prevalence of
      polypharmacy and FRIDS in older patients discharged from an Orthogeriatric Unit
      after a hip fracture surgery. METHODS: This study describes the baseline findings
      of a 2-year retrospective cohort study. We included patients older than 80 years
      discharged from an Orthogeriatric Unit who were able to walk before surgery.
      Patient's baseline variables, total number of drugs, and FRIDS at hospital
      discharge were collected. RESULTS: We included 228 patients. The mean number of
      drugs and FRIDS prescribed at discharge was 11.6 +/- 3.0 and 2.9 +/- 1.6,
      respectively. Polypharmacy was prevalent in all patients except in three: 23.3%
      (5-9 drugs) and 75.9% (>= 10 drugs). Only 11 patients had no FRIDS and 35.5% were
      on > 3 FRIDS. The most prevalent FRIDS were: agents acting on the renin
      angiotensin system (43.9%) and anxiolytics (39.9%). The number of FRIDS was
      higher in patients with extreme polypharmacy (3.4 +/- 1.5) than in those on 5-9
      drugs (1.5 +/- 1.0, p < 0.05). Independent people in performing instrumental
      activities had lower risk of extreme polypharmacy (>= 10 drugs) or > 3 FRIDS: OR
      0.39 (95% CI 0.18-0.83) and OR 0.41 (95% CI 0.20-0.84), respectively. People
      living in a nursing home had higher risk of > 3 FRIDS: OR 4.03 (95% CI 1.12
      14.53). CONCLUSIONS: Polypharmacy and fall-risk increasing drugs are prevalent in
      patients discharged from orthogeriatric care after surgery for a hip fracture.
      Interventions on drug use at hospital discharge could have a potential impact on
      falls in this high-risk population.

PMID- 30276632
TI  - Year to year comparison of 2000-2015 in hip fracture management: same survival
      rate despite older and more fragile patients.
AB  - PURPOSE: The aim of this study was to compare clinical data, comorbidities and
      survival rates at 30 days and 1 year in two groups with femoral fractures, the
      first including patients admitted in 2000, and the other including patients
      admitted in 2015. The hypothesis of the study is that patients admitted in 2015
      have more comorbidities and will therefore have a lower survival rate at 30 days
      and 1 year from trauma. METHODS: Patients admitted to the hospital with proximal
      femoral fractures in 2000 (90 patients) and 2015 (167 patients) were
      retrospectively reviewed. The following data were collected: age, gender, source
      of admission, ASA score, comorbidities, time from admission to surgery and length
      of hospital stay. The Charlson Comorbidity Index (CCI) score, a measure of
      comorbidity, and the Nottingham Hip Fracture Score (NHFS), a predictor of 30-day
      and 1-year mortality after hip fracture, were both calculated. RESULTS: Patients
      in the 2015 group were older and more institutionalized before fracture (p <
      0.05), with a significant increase in Alzheimer's disease, chronic obstructive
      pulmonary disease, congestive heart failure and renal impairment. The length of
      stay was significantly lower in 2015. The NHFS and CCI were significantly higher
      in 2000. Mortality at 30 days and 1 year did not differ significantly in 2000
      when compared to 2015. The CCI had the best predictive ability for mortality in
      both groups at 30 days and 1 year. CONCLUSIONS: The increase of comorbidities was
      not found to be correlated to increased mortality. This could be explained by
      enhanced patient management permitting earlier mobilization and weight bearing.

PMID- 30276633
TI  - Prevalence and related factors of office and home hypotension in older treated
      hypertensive patients.
AB  - BACKGROUND: Older hypertensive adults under treatment are especially susceptible
      to hypotensive episodes, which entail an elevated risk. However, data on this
      subject are very scarce. AIM: The purpose of this study was to determine the
      prevalence and predictors of office and home hypotension in older (>= 65 years)
      treated hypertensive adults. METHODS: Blood pressure (BP) was measured at the
      office and at home, using a validated oscillometric device. Office and home
      hypotension were defined as systolic BP (SBP) < 110 and/or diastolic BP (DBP) <
      70 mmHg, and SBP < 105 and/or DBP < 65 mmHg, respectively. Masked hypotension was
      considered when office BP >= 110/70 and home BP < 105 and/or < 65 mmHg. We
      evaluated factors associated with hypotension both at the office and at home
      through multivariable models. RESULTS: The prevalence of hypotension among the
      302 patients included in the study was 29.8% at the office and 23.9% at home,
      whereas the prevalence of masked hypotension was 10.4%. Older age, lower body
      mass index and use of calcium channel blockers were associated with office
      hypotension, while older age, diabetes and ischemic heart disease were predictors
      for home hypotension. CONCLUSION: Hypotension is frequent in older hypertensive
      adults under treatment. The presence of diabetes, ischemic heart disease and
      older age should alert for screening of hypotension at home to avoid
      overtreatment.

PMID- 30276634
TI  - Technical approach of robotic total right hepatic lobectomy: How we do it?
AB  - Despite advantages of minimally invasive surgery, many hepatobiliary surgeons are
      hesitant to offer this approach for major hepatic resection due to concerns of
      difficulty in liver manipulation, bleeding control, and suboptimal oncologic
      outcomes. The robotic surgical system has revolutionized the way traditional
      laparoscopic liver resection is undertaken. Limitations of traditional
      laparoscopy are being resolved by robotic technology. We aimed to describe
      aspects of minimally invasive liver surgery and our standardized technical
      approach. We discussed technical aspects of performing robotic total right
      hepatic lobectomy and described our standardized institutional method. A 79-year
      old man with an 11-cm biopsy-proven hepatocellular carcinoma was taken to the
      operating room for a robotic total right hepatic lobectomy. Past medical and
      surgical history was consistent with hypertension and diabetes mellitus. Robotic
      extrahepatic Glissonean pedicle approach was used to gain inflow vascular
      control. Right hepatic artery and portal vein were individually dissected and
      isolated prior to division. An intraoperative robotic ultrasound was utilized to
      guide liver parenchymal transection, securing negative margins. Robotic vessel
      sealing device was used as the main energy device during the parenchymal
      transection. Right hepatic vein was transected intrahepatically using a linear
      stapler. Operative time was 200 min without intraoperative complications.
      Estimated blood loss was 100 ml. Postsurgical recovery was uneventful and he was
      discharged home on postoperative day 4. Minimally invasive robotic total right
      hepatic lobectomy is feasible with excellent perioperative outcomes.

PMID- 30276635
TI  - Quality improvement as a population health promotion opportunity to reorient the
      healthcare system.
AB  - BACKGROUND: A quality improvement (QI) focus in systems strategically investing
      resources to achieve the Quadruple Aim (i.e., better population health, lower
      system costs, improved patient care, and an engaged and productive workforce)
      presents an opportunity to reorient health services towards population health
      promotion. SETTING: An interdisciplinary team linked across a large regionalized
      healthcare system engaged in a (Saskatoon) Region-wide 90-day QI initiative
      focused on patient safety. INTERVENTION: The team worked directly with healthcare
      teams to link cultural safety, patient-centeredness, and health equity to other
      dimensions of healthcare quality. The team provided data from health status
      reports, equity analyses of healthcare utilization, and stakeholder consultations
      and adapted QI methods, including A3 thinking and Plan-Do-Check-Act (PDCA)
      cycles. OUTCOMES: Throughout the 90 days, use of the terms "health equity" and
      "cultural safety" increased among healthcare teams and in region-wide
      communications. Within the year following the initiative, the Region made public
      and ongoing commitments to address health inequities. IMPLICATIONS: System-wide
      QI initiatives present opportunities to promote population health approaches,
      shift perspectives and language, and ultimately influence organizational culture.
      Learnings are relevant to health promotion practitioners attempting to engage
      healthcare partners, and for health systems strategically investing for improved
      population health.

PMID- 30276636
TI  - A modeling study exploring the impact of homelessness on rostered primary care
      utilization in Calgary, Canada.
AB  - OBJECTIVE: For patients who belonged to physician rosters at a family medicine
      practice in the core of Calgary, Canada, we compared primary care utilization for
      those who were stably housed and those experiencing homelessness. METHODS: This
      retrospective chart review accessed electronic medical record data for rostered
      patients who visited their family physician between July 1, 2015 and August 31,
      2016. We assessed the association between homelessness status (defined as having
      been sheltered in overnight shelters and/or emergency/provisional housing during
      the study period) and the rate of visits to primary care (defined as the count of
      visits associated with a patient accounting for the length of the patient's
      relationship with their family physician) using multivariate negative binomial
      regression. RESULTS: We analyzed 1013 patients belonging to three family
      physician rosters, of whom 112 experienced homelessness during the study period
      (11.1%). The mean number of visits for patients who experienced homelessness was
      9.6 (SD 10.5), compared to 4.2 (SD 3.6) visits for stably housed patients (p <
      0.0001). The rate of accessing primary care for patients experiencing
      homelessness was 2.02 times greater than the rate for stably housed individuals
      (rate ratio [RR] 2.02, 95% confidence interval [95% CI] 1.74-2.35; p < 0.0001).
      CONCLUSION: In the context of an inner-city primary care clinic in Calgary,
      Canada, homelessness status is associated with an increased rate of visits to
      primary care. This work has implications for public health and health systems
      decision-makers involved in developing equitable health policy, as well as for
      frontline care providers who serve this vulnerable population.

PMID- 30276637
TI  - Differences in Injury Characteristics and Outcomes for American Indian/Alaska
      Native People Hospitalized with Traumatic Injuries: an Analysis of the National
      Trauma Data Bank.
AB  - OBJECTIVE: This study compares characteristics of American Indian/Alaska Natives
      (AI/AN) and non-Hispanic Whites (NHW) hospitalized for traumatic injury and
      examines the effect of race on hospital disposition. METHODS: Using 2007-2014
      National Trauma Data Bank data, we described differences in demographic and
      injury characteristics between AI/AN (n = 39,656) and NHWs (n = 3,309,484)
      hospitalized with traumatic injuries. Multivariable regressions, adjusted for
      demographic and injury characteristics, compared in-hospital mortality and the
      risk of discharge to different dispositions (inpatient rehabilitation/long-term
      care facility, skilled nursing facility, home with home health services) rather
      than home between AI/AN and NHW patients. RESULTS: Compared to NHWs, a higher
      proportion of AI/ANs were age 19-44 (49% versus 27%) years and hospitalized with
      assault-related injuries (25% versus 5%). AI/ANs had lower odds of dying than
      NHWs during hospitalization (adjusted odds ratio (aOR) 0.72, 95% CI 0.63-0.84).
      However, AI/ANs also had lower odds than NHWs to discharge to locations with
      additional health services even after controlling for injury severity (inpatient
      rehabilitation/long-term care facilities aOR 0.79, 95% CI 0.67-0.93; skilled
      nursing facility aOR 0.70, 95% CI 0.49-0.98; home with home health services aOR
      0.62, 95% CI 0.49-0.79). CONCLUSIONS: Injury patterns and acute hospitalization
      outcomes were significantly different for AI/ANs compared to NHWs. Injury
      prevention strategies targeting AI/ANs should reflect these differential injury
      patterns. Outcomes such as disability and access to rehabilitation services
      should be included when considering the burden of injury among AI/AN communities.

PMID- 30276638
TI  - Probabilistic retro-cues do not determine state in visual working memory.
AB  - The effective use of our capacity-limited visual working memory (VWM) requires
      mechanisms that govern how it represents information. Validly cueing an item in
      VWM after encoding, for instance, enhances memory performance for that item and
      biases its state in VWM, bringing its representation to an active state such that
      attentional selection is biased towards perceptually similar inputs. Critically,
      when the retro-cue is less than 100% valid (i.e., probabilistic rather than
      deterministic), the effect of the cue on memory performance varies. Here we
      investigated whether deterministic and probabilistic retro-cues also differ in
      their influence over item state in VWM. Participants encoded two colored squares,
      and a retro-cue indicated which item was most likely to be probed in a subsequent
      memory test. Across blocks, we manipulated cue validity to be deterministic (100%
      valid) or probabilistic (70% valid). On a subset of trials, no memory probe was
      presented and the trial ended with a visual search task in which a colored
      distractor -matching the cued memory item, the non-cued item, or neither - was
      presented. Predictably, in the deterministic condition, the presence of a
      singleton distractor matching the cued item reliably slowed reaction times during
      visual search. In the probabilistic condition, however, there were no differences
      in reaction times when the singleton matched the cued item or the non-cued item,
      despite a reliable benefit to memory performance on valid memory trials. We
      suggest that, while probabilistic retro-cues improve memory of the cued item,
      they are not sufficient to bias its state in VWM.

PMID- 30276639
TI  - Learning by Example: An International Perspective on Reflex-Testing for Lynch
      Syndrome.
AB  - BACKGROUND: Lynch syndrome (LS), an autosomal dominant cancer syndrome, is the
      most common cause of hereditary colon cancer. Currently, however, less than 5% of
      patients with LS have been identified. Reflex-testing programs (in which tumors
      of patients with colorectal cancer are routinely evaluated for LS) have been
      proposed for better identification of affected individuals, yet the uptake of
      these programs within health care systems is limited. This study explored the
      structure, implementation challenges, and future directions of existing
      international population-based reflex LS testing programs. METHODS: The study
      identified existing reflex-testing LS programs through the current literature and
      through a qualitative sampling approach. Key informants from each program were
      interviewed. Qualitative data were analyzed using a grounded theory analytic
      technique approach. RESULTS: The interviews were completed by 26 informants
      across seven identified programs. Three key themes were identified: (1) tension
      between a program imposed on stakeholders (a top-down approach) versus initiation
      of the program at the stakeholder level (bottom-up approach), (2) identification
      of pathologists as drivers of program success, and (3) strategies to optimize
      possible LS patients liaising with genetic counselors. Barriers to successful
      implementation included lack of stakeholder engagement and concerns regarding
      cost. Facilitators included strong administration to coordinate patient tracking
      and flexibility during the implementation process. CONCLUSIONS: Existing reflex
      testing LS programs have varying structures, standards, and protocols. Program
      design can have a direct effect on the uptake of genetic testing. These are
      important considerations in the large-scale planning of LS reflex-testing
      programs within health systems.

PMID- 30276640
TI  - ASO Author Reflections: Should We Be Using Dextrose-Containing Carrier Solutions
      for Perfusion During HIPEC?

PMID- 30276641
TI  - Are Staging Computed Tomography (CT) Scans of the Chest Necessary in Pancreatic
      Adenocarcinoma?
AB  - BACKGROUND: There is no consensus on the use of chest imaging in pancreatic
      ductal adenocarcinoma (PDAC) patients. Among PDAC patients, we examined the use
      of chest computed tomography (CT) over time and determined whether the use of
      chest CT led to a survival difference or change in management via identification
      of indeterminate lung nodules (ILNs). METHODS: Retrospective clinical data was
      collected for patients diagnosed with PDAC from 1998 to 2014. We examined the
      proportion of patients undergoing staging chest CT scan and those who had ILN,
      defined as >= 1 well-defined, noncalcified lung nodule(s) <= 1 cm in diameter. We
      determined time to overall survival (OS) using multivariate Cox regression. We
      also assessed changes in management of PDAC patients who later developed lung
      metastasis only. RESULTS: Of the 2710 patients diagnosed with PDAC, 632 (23%) had
      greater than one chest CT. Of those patients, 451 (71%) patients had ILNs,
      whereas 181 (29%) had no ILNs. There was no difference in median overall survival
      in patients without ILNs (16.4 [13.6, 19.0] months) versus those with ILN (14.8
      [13.6, 15.8] months, P = 0.18). Examining patients who developed isolated lung
      metastases (3.3%), we found that staging chest CTs did not lead to changes in
      management of the primary abdominal tumor. CONCLUSIONS: Survival did not differ
      for PDAC patients with ILNs identified on staging chest CTs compared with those
      without ILNs. Furthermore, ILN identification did not lead to changes in
      management of the primary abdominal tumor, questioning the utility of staging
      chest CTs for PDAC patients.

PMID- 30276642
TI  - A New N Staging System for Colorectal Cancer in the Era of Extended
      Lymphadenectomy.
AB  - BACKGROUND: Complete mesocolic excision is becoming popular in colon cancer
      surgery in Western countries, and in the tumor-node-metastasis (TNM)
      classification of rectal cancer, a part of the lateral pelvic lymph nodes is
      classified as regional. However, the appropriateness of TNM staging according to
      the assessment of nodal status exclusively by extended lymphadenectomy remains
      unclear. PATIENTS AND METHODS: Using a nationwide multicenter database in Japan,
      we retrospectively analyzed 6866 patients with stage III colorectal cancer (CRC)
      treated with extended (D3) dissection. First, the best cutoff values for the
      number of metastatic nodes were explored. Second, the utility of the metastatic
      status of the main lymph nodes (i.e., at the origin of the feeding artery) and
      the lateral pelvic lymph nodes ("jN3" category in the Japanese staging system) as
      N staging criteria was evaluated. The modified N staging system that had the best
      risk stratification power was determined according to the Akaike information
      criterion (AIC). RESULTS: Excellent performance was noted when the number of
      metastatic nodes was categorized by cutoff values of "3/4" and "6/7."
      Categorization of nodal metastasis was proven the most clinically efficacious
      when classified as modified-N1 (N1 and jN3-negative), modified-N2a (N2a and jN3
      negative), and modified-N2b (N2b and/or jN3-positive; AIC, 22,810.8), rather than
      the classification based on the TNM (AIC, 22,849.2) or Japanese staging system
      (AIC, 22,811.1). CONCLUSIONS: We structured a modified N staging system according
      to the number and extent of lymph node metastases. The modified system may be
      used in stage III cases for precise risk stratification.

PMID- 30276643
TI  - Blood Transfusion in Cytoreductive Surgery: Better Not at All.

PMID- 30276644
TI  - Air Bubble Sign: ANew Screening Method for Anastomotic Leakage After
      Esophagectomy for Esophageal Cancer.

PMID- 30276645
TI  - Does p16+ Predict a Favorable Prognosis for Oropharyngeal Cancer? Risk Factors
      for Treatment Failure for Patients Who Underwent Surgery-Based Therapy.
AB  - BACKGROUND: This study aimed to identify prognostic clinicopathologic factors
      that could predict treatment failure and to analyze clinical data from p16+
      oropharyngeal squamous cell carcinoma (OPSCC) patients who underwent surgery.
      METHODS: Data from p16+ OPSCC patients who underwent surgery at Severance
      Hospital of Yonsei University were retrospectively reviewed. RESULTS: The average
      smoking history was 14.6 pack-years (range 0-94 pack-years). Of the 188 patients,
      73 (38.8%) underwent transoral robotic surgery (TORS) for surgical treatment of
      their primary lesions, and the remaining 115 patients (61.2%) underwent
      conventional surgery. Extracapsular nodal spread was detected in 87 patients
      (46.3%). At histologic examination, 67 patients (35.6%) showed positive surgical
      margins, and 121 patients (64.4%) had negative surgical margins. Postoperative
      adjuvant treatment was performed for 167 patients (88.8%). During the follow-up
      period, there were 18 recurrences including 2 local recurrences, 10 regional
      recurrences, and 6 distant metastases. During the study period, 17 deaths
      occurred. The univariate analysis showed that the American Joint Committee on
      Cancer (AJCC) 8th-edition staging system, lymphovascular invasion, more than four
      metastatic lymph nodes, and a smoking history of more than 10 pack-years were
      significantly associated with treatment failure. In the multivariate analysis,
      only the AJCC 8th-edition staging system was significantly associated with the
      patient's survival. CONCLUSION: Surgical treatment methods including TORS for
      p16+ OPSCC patients showed excellent oncologic results, and many previously known
      clinicopathologic factors did not show a significant relationship with patient
      prognosis. Only the newly revised AJCC 8th-edition staging system showed a
      significant relationship with patient survival, and this should be considered in
      the setting of p16+ OPSCC treatment guidelines in the future.

PMID- 30276646
TI  - Perioperative and Long-Term Outcomes of Laparoscopic Versus Open Lymphadenectomy
      for Biliary Tumors: A Propensity-Score-Based, Case-Matched Analysis.
AB  - BACKGROUND: The purpose of this study was to compare patients undergoing MILS and
      open liver resections with associated lymphadenectomy for biliary tumors
      (intrahepatic cholangiocarcinoma and gallbladder cancer) in a case-matched
      analysis using propensity scores. METHODS: A total of 104 consecutive patients
      underwent liver resection with associated locoregional lymphadenectomy by
      laparoscopic approach constituted the study group (MILS group). The MILS group
      was matched in a ratio of 1:2 with patients who had undergone open resection for
      primary biliary cancers (Open group). Short- and long-term outcomes were
      evaluated and compared, with specific focus on specific details of
      lymphadenectomy. RESULTS: Laparoscopic series resulted in a statistically
      significant lower blood loss (200 vs. 350, p = 0.03), minor intraoperative blood
      transfusions (3.2% vs. 7.9%, p = 0.04), and postoperative blood transfusions
      (10.5% vs. 15.8%), other than shorter length of stay (4 vs. 6 days, p = 0.04).
      Number of retrieved nodes was 8 versus 7 (p = not significant); particularly,
      percentage of patients who achieved the recommended AJCC cutoff of six lymph
      nodes harvested were 93.7% versus 85.8% (p = 0.05). Both overall and
      lymphadenectomy-related morbidity (bleeding, pancreatitis, lymphatic fistula,
      vascular, and biliary injuries) were lower in MILS group (respectively 16.3% and
      3.2% vs. 22.1% and 5.3%, p = 0.03). Median disease-free survival was 33 versus 36
      months and disease recurrence occurred in 45.3% versus 55.3% of patients in MILS
      and Open groups respectively. CONCLUSIONS: Laparoscopic approach for
      lymphadenectomy is a valid option in patients with biliary cancers, because it
      allows to maintain the advantages of minimally invasive approach, without
      compromising the accuracy and the outcomes of nodal dissection.

PMID- 30276647
TI  - Intraoperative Electron Radiation Therapy Combined with External Beam Radiation
      Therapy after Gross Total Resection in Extremity Soft Tissue Sarcoma: A European
      Pooled Analysis.
AB  - INTRODUCTION: We report a pooled analysis evaluating the combination of gross
      complete limb-sparing surgery, intraoperative electron radiation therapy (IOERT),
      and external beam radiation therapy (EBRT) in patients with extremity soft tissue
      sarcoma (STS). METHODS: Individual data of 259 patients (median follow-up 63
      months) with extremity STS from three European expert centers were pooled. Median
      age was 55 years and median tumor size was 8 cm. Eighty percent of patients
      presented with primary disease, mainly located in the lower limb (81%). Union for
      International Cancer Control 7th edition stage at presentation was as follows:
      stage I: 9%; stage II: 47%; stage III: 39%; stage IV: 5%. Most patients showed
      high-grade lesions (91%), predominantly liposarcoma (31%). Median IOERT dose was
      12 Gy, preceeded (17%) or followed (83%) by EBRT, with a median dose of 45 Gy.
      RESULTS: Surgery resulted in R0 resections in 71% of patients and R1 resections
      in 29% of patients. The 5-year local control (LC) rate was 86%, and significant
      factors in univariate analysis were disease status and resection margin. Only
      margin remained significant in multivariate analysis. The 5-year distant control
      rate was 69%, and significant factors in univariate analysis were histology,
      grading, resection margin, and metastases prior to/at IOERT. Only grading and
      metastases remained significant in multivariate analysis. Actuarial 5-year rates
      of freedom from treatment failure and OS were 61% and 78%, respectively.
      Significant factors for OS were grading and metastases prior to/at IOERT
      (univariate, multivariate). Limb preservation and good functional outcome were
      achieved in 95% and 81% of patients. CONCLUSIONS: Our pooled analysis confirmed
      prior reports of encouraging LC and survival, with excellent rates of preserved
      limb function with this treatment approach. Resection margin remained the most
      important factor for LC, while grading and metastases prior to/at IOERT mainly
      predicted survival.

PMID- 30276648
TI  - Ascorbic acid-induced oxalate nephropathy: a case report and discussion of
      pathologic mechanisms.
AB  - Oxalate nephropathy is associated with hereditary hyperoxaluria, Crohn disease,
      and previous gastric or intestinal surgery, especially in the setting of
      increased oxalate intake or ethylene glycol ingestion. We present a patient whose
      intake of vitamin C supplements (2 g/day), exacerbated by predisposing factors of
      prior small bowel obstruction and resection, and benign prostate hyperplasia
      (BPH), resulted in acute kidney injury due to oxalate nephropathy. We review past
      reports of vitamin C-induced oxalate nephropathy and discuss the underlying
      precipitating factors.

PMID- 30276649
TI  - Pre-eclampsia: the role of highly active antiretroviral therapy and immune
      markers.
AB  - PURPOSE OF THE REVIEW: This review highlights the role immune cells and markers
      such as natural killer (NK) cells, cytokines and human leukocyte antigen (HLA-G)
      play in predisposing HIV-infected women who are on HAART to develop PE, thus
      contributing to a better understanding and early diagnosis of PE with a
      subsequent reduction in maternal foetal and neonatal deaths. RECENT FINDINGS:
      Pregnant women infected with the Human Immunodeficiency Virus (HIV) have a 25%
      risk of mother to child transmission. This risk, however, decreases to 2% if the
      women is on treatment. Highly active antiretroviral therapy (HAART) is the
      recommended treatment for both pregnant and non-pregnant women infected with HIV.
      Treatment with HAART is reported to potentiate predisposition to the development
      of hypertensive disorders of pregnancy such as pre-eclampsia (PE). Pre-eclampsia
      accounts for 7-10% of abnormal pregnancies worldwide. Studies demonstrate that
      pregnant women with HIV have PE at lower frequencies than uninfected women,
      however, the converse is observed upon HAART initiation. HIV-infected women on
      HAART exhibit a greater tendency to develop PE, emanating from immune
      reconstitution induced by HAART. There is paucity of information as to the
      pathogenesis of PE upon HAART initiation and there are, therefore, controversial
      data as to whether HAART predisposes women to a lower, equal or higher risk of PE
      development compared to the general population, further investigations on the
      impact of HIV infection and HAART on the immune response and rate of PE
      development in HIV infected pregnant women are urgently needed.

PMID- 30276650
TI  - Atlanto-axial rotatory fixation complicating ventriculo-peritoneal shunt surgery:
      a case report and literature review.
AB  - INTRODUCTION: Atlanto-axial rotatory fixation (AARF) is a rare complication of
      ventriculo-peritoneal shunt (VPS) surgery. CASE PRESENTATION: The authors present
      a unique case of AARF developing early after VP shunting, with persistent
      torticollis, a "cock-robin" head position, and a thick fibrous band along the
      catheter path. Due to refractoriness to conservative treatments, AARF, which can
      be an early-onset complication of VPS surgery, was resolved by removing the
      distal catheter along with the fibrous band encasing it. CONCLUSION: Surgical
      removal of the fibrous band might be enough to solve such complication with no
      need of further surgical fusion procedures.

PMID- 30276652
TI  - Conservative and operative management of iatrogenic craniocerebral disproportion
      a case-based review.
AB  - INTRODUCTION: Craniocerebral disproportion (CCD) can occur as a sequela after
      shunting in early infancy. It can be understood as a disorder closely related to
      slit ventricle syndrome and chronic overdrainage syndrome. Here, we present two
      exemplary cases and summarize the pathophysiological, diagnostic, and therapeutic
      approaches to CCD. CLINICAL PRESENTATION: Two premature babies underwent shunting
      for posthemorrhagic hydrocephalus and presented in later childhood with recurrent
      episodes of symptomatic raised intracranial pressure (ICP) at 2 and 8 years of
      age, respectively. DIAGNOSIS AND MANAGEMENT: Both patients had unchanged
      ventricular size on cranial imaging and fulfilled the clinical diagnostic
      criteria of CCD. After confirming shunt patency, ICP monitoring was performed to
      diagnose intermittent intracranial hypertension. Different treatment pathways
      were pursued: While readjustment of a programmable shunt valve was sufficient to
      alleviate the raised ICP in the first case, a cranial expansion surgery was
      necessary in the second case. OUTCOME AND CONCLUSIONS: Both children were treated
      successfully after thorough assessment and careful choice of treatment
      approaches. This review provides detailed insight into CCD and highlights the
      importance of individual and critical decision-making in these complex patients.

PMID- 30276651
TI  - Cognitive functioning of pediatric patients with brain tumor: an investigation of
      the role of gender.
AB  - PURPOSE: The female gender has been considered a risk factor for cognitive
      impairment in pediatric brain tumor survivors. However, it is still unknown which
      specific cognitive domains are at greater risk of impairment in females. The aim
      of this study was to explore differences between male and female children in
      distinct domains of cognitive functioning, in order to deepen knowledge on the
      topic. METHODS: The cognitive performance of 100 males and 71 females aged 6-16
      years was assessed by Wechsler Intelligence Scales for Children-Third Edition
      (WISC-III). Differences between males and females were tested not only on
      intellectual quotients, but also on WISC-III subtests, which allow the evaluation
      of different cognitive domains. Analyses were performed in the whole sample and
      dividing children based on the supratentorial vs. infratentorial location of the
      tumor. RESULTS: Gender was the only predictor of VIQ in the whole group and in
      children with supratentorial tumor. Female children with supratentorial tumor
      performed significantly worse than males in four out of six verbal subtests.
      However, even among children with infratentorial tumor, females performed worse
      than males on two verbal subtests. CONCLUSIONS: Overall, findings of this study
      suggest that females may have more difficulties than males at manipulating verbal
      oral material. A possible explanation of these findings could be that females
      present a greater vulnerability to white matter damage due to the illness and
      post-adjuvant therapies, in line with reports of the literature on female
      children with lymphoblastic leukemia.

PMID- 30276653
TI  - Octopicola huanghaiensis n. sp. (Copepoda: Cyclopoida: Octopicolidae), a new
      parasitic copepod of the octopuses Amphioctopus fangsiao (d'Orbigny) and Octopus
      minor (Sasaki) (Octopoda: Octopodidae) in the Yellow Sea.
AB  - A new species of parasitic copepod, Octopicola huanghaiensis n. sp., collected
      from the octopuses Amphioctopus fangsiao (d'Orbigny) and Octopus minor (Sasaki)
      (Octopoda: Octopodidae) in the Yellow Sea (off Qingdao, Shandong Province,
      China), is described. The new species is most similar to O. superba Humes, 1957,
      but can be distinguished from the latter by: (i) the third antennal segment
      having a different ornamentation; (ii) the fourth antennal segment of females
      much shorter than that in O. superba (49 vs 94 MUm); (iii) males much smaller
      than females (mean body length 1.3 vs 2.0 mm, respectively) (vs similar male and
      female body size in O. superba, 1.9 mm and 1.8 mm respectively); and (iv) the
      presence of a spike at the posterior tip of each labrum flap. Octopicola
      huanghaiensis n. sp. is the first species of Octopicola Humes, 1957 reported from
      A. fangsiao and O. minor and is the only species of the family Octopicolidae
      Humes & Boxshall, 1996 known in North Pacific waters.

PMID- 30276654
TI  - Burnout Among Physicians, Advanced Practice Clinicians and Staff in Smaller
      Primary Care Practices.
AB  - BACKGROUND: Burnout among primary care physicians, advanced practice clinicians
      (nurse practitioners and physician assistants [APCs]), and staff is common and
      associated with negative consequences for patient care, but the association of
      burnout with characteristics of primary care practices is unknown. OBJECTIVE: To
      examine the association between physician-, APC- and staff-reported burnout and
      specific structural, organizational, and contextual characteristics of smaller
      primary care practices. DESIGN: Cross-sectional analysis of survey data collected
      from 9/22/2015-6/19/2017. SETTING: Sample of smaller primary care practices in
      the USA participating in a national initiative focused on improving the delivery
      of cardiovascular preventive services. PARTICIPANTS: 10,284 physicians, APCs and
      staff from 1380 primary care practices. MAIN MEASURE: Burnout was assessed with a
      validated single-item measure. KEY RESULTS: Burnout was reported by 20.4% of
      respondents overall. In a multivariable analysis, burnout was slightly more
      common among physicians and APCs (physician vs. non-clinical staff, adjusted odds
      ratio [aOR] = 1.26; 95% confidence interval [CI], 1.05-1.49, APC vs. non-clinical
      staff, aOR = 1.34, 95% CI, 1.10-1.62). Other multivariable correlates of burnout
      included non-solo practice (2-5 physician/APCs vs. solo practice, aOR = 1.71; 95%
      CI, 1.35-2.16), health system affiliation (vs. physician/APC-owned practice, aOR
      = 1.42; 95%CI, 1.16-1.73), and Federally Qualified Health Center status (vs.
      physician/APC-owned practice, aOR = 1.36; 95%CI, 1.03-1.78). Neither the
      proportion of patients on Medicare or Medicaid, nor practice-level patient volume
      (patient visits per physician/APC per day) were significantly associated with
      burnout. In analyses stratified by professional category, practice size was not
      associated with burnout for APCs, and participation in an accountable care
      organization was associated with burnout for clinical and non-clinical staff.
      CONCLUSIONS: Burnout is prevalent among physicians, APCs, and staff in smaller
      primary care practices. Members of solo practices less commonly report burnout,
      while members of health system-owned practices and Federally Qualified Health
      Centers more commonly report burnout, suggesting that practice level autonomy may
      be a critical determinant of burnout.

PMID- 30276656
TI  - What I Would Do.

PMID- 30276655
TI  - Insurance Coverage Predicts Mortality in Patients Transferred Between Hospitals:
      a Cross-Sectional Study.
AB  - BACKGROUND: Patients transferred between hospitals are at high risk of adverse
      events and mortality. The relationship between insurance status, transfer
      practices, and outcomes has not been definitively characterized. OBJECTIVE: To
      identify the association between insurance coverage and mortality of patients
      transferred between hospitals. DESIGN: We conducted a single-institution
      observational study, and validated results using a national administrative
      database of inter-hospital transfers. SETTING: Three ICUs at an academic tertiary
      care center validated by a nationally representative sample of inter-hospital
      transfers. PATIENTS: The single-institution analysis included 652 consecutive
      patients transferred from 57 hospitals between 2011 and 2012. The administrative
      database included 353,018 patients transferred between 437 hospitals.
      MEASUREMENTS: Adjusted inpatient mortality and 24-h mortality, stratified by
      insurance status. RESULTS: Of 652 consecutive transfers to three ICUs, we
      observed that uninsured patients had higher adjusted inpatient mortality (OR
      2.67, p = 0.021) when controlling for age, race, gender, Apache-II, and whether
      the patient was transferred from an ED. Uninsured were more likely to be
      transferred from ED (OR 2.3, p = 0.026), and earlier in their hospital course
      (3.9 vs 2.0 days, p = 0.002). Using an administrative dataset, we validated these
      observations, finding that the uninsured had higher adjusted inpatient mortality
      (OR 1.24, 95% CI 1.13-1.36, p < 0.001) and higher mortality within 24 h (OR 1.33
      95% CI 1.11-1.60, p < 0.002). The increase in mortality was independent of
      patient demographics, referral patterns, or diagnoses. LIMITATIONS: This is an
      observational study where transfer appropriateness cannot be directly assessed.
      CONCLUSIONS: Uninsured patients are more likely to be transferred from an ED and
      have higher mortality. These data suggest factors that drive inter-hospital
      transfer of uninsured patients have the potential to exacerbate outcome
      disparities.

PMID- 30276657
TI  - Geographic Trends for United States Allopathic Seniors Participating in the
      Residency Match: a Descriptive Analysis.

PMID- 30276658
TI  - Job Negotiations in Academic Medicine: Building a Competency-Based Roadmap for
      Residents and Fellows.
AB  - Negotiation skills are critical to career success, yet many physicians feel ill
      equipped to negotiate for professional opportunities. Enhancing competencies in
      this arena may be especially critical for women and underrepresented minorities
      to reduce disparities in compensation and resources that begin upon entry into
      the workforce as junior faculty. This perspective offers a comprehensive overview
      of negotiation strategies and the job search process for individuals finishing
      medical training and seeking first-time employment. First, we extrapolate lessons
      from clinical medicine to provide a negotiation roadmap for residents and
      fellows. We use both a clinical and an employment scenario to illustrate the
      concept of principled negotiation in which negotiating partners elicit each
      other's values and interests and identify options for mutual gain. We then
      describe approaches to seeking and negotiating job opportunities and discuss
      typical timelines for these activities. We supply a list of professional needs to
      consider before a negotiation begins and introduce the concept of a best
      alternative to negotiated agreement to help ensure essential requirements are met
      in a final employment offer. Finally, we explore the utility of third-party
      assistance and published benchmarks and offer best practices for negotiating.

PMID- 30276659
TI  - Position paper of the Italian Society of Internal Medicine (SIMI) on prophylaxis
      and treatment of venous thromboembolism in patients with cancer.
AB  - Cancer patients are at high risk of developing thrombotic events, including
      venous thromboembolism (VTE) [deep venous thrombosis (DVT) and pulmonary embolism
      (PE)], and arterial thrombosis. DVT and PE represent the second leading cause of
      death in cancer patients; moreover, the development of thromboembolic events in
      cancer patients is linked to a greater need of hospitalization and frequency of
      side effects during treatment, in particular bleeding, and to an increased risk
      of recurrence during and following antithrombotic therapy. The thromboembolic
      risk may be different in different subgroups of cancer population, being highest
      in patients with metastatic disease, patients with pancreas, stomach, kidney or
      primary brain cancer, or during therapeutic interventions or surgery. This
      document focuses on several relevant topics including the epidemiology and
      pathogenesis of cancer-associated VTE, the current and future strategies of
      primary prevention and anticoagulant treatment, and the management of bleeding
      complications. The main literature data are discussed in detail, including, when
      available, evidence from randomized clinical trials and meta-analyses,
      international guidelines statements, the results of recently published trials
      comparing direct oral anticoagulants to low molecular weight heparin, and the
      design and aims of ongoing trials on prevention/treatment of cancer-associated
      VTE.

PMID- 30276660
TI  - A simple treatment for a potentially life-threatening cause of malabsorption.

PMID- 30276661
TI  - Red cell distribution width predicts mid-term prognosis in patients hospitalized
      with acute heart failure: the RDW in Acute Heart Failure (RE-AHF) study.
AB  - The aim of the study was to evaluate the prognostic role of red cell distribution
      width (RDW) in a broad population of patients hospitalized for acute heart
      failure (AHF). In a retrospective cohort observational study, 451 consecutive
      patients discharged for AHF were categorized in patients with low RDW (<= 14.8%)
      and high RDW (> 14.8%). The rates of death from all causes or of hospital
      readmission for worsening heart failure and death were determined after a median
      follow-up of 18 months. The overall population has a median age of 80 years (IQR
      72-85), 235 patients (52%) were males. Patients with a higher RDW have more
      comorbidities and a higher Charlson Index. At follow-up, 200 patients (44%) had
      died and 247 (54%) had died or were readmitted for HF: in the cohort with low
      RDW, 70 patients (36.4%) had died, whereas in the cohort with high RDW, 165
      patients (63.7%) had died: the unadjusted risk ratio of patients with high RDW
      was 2.03 (log-rank test: p < 0.0001). In a multivariate Cox regression model, the
      hazard ratio for death from any cause in the 'high RDW' cohort is 1.73 (95%
      confidence interval 1.2-2.48; p = 0.003); the RDW adds prognostic information
      beyond that provided by conventional predictors, including age; etiology of HF;
      anemia; hyponatremia; estimated glomerular filtration rate; NT-proBNP levels;
      Charlson comorbidity score, atrial fibrillation, functional status, therapy with
      renin-angiotensin-aldosterone system inhibitors, beta-blockers. RDW is a powerful
      marker of worse long-term outcomes in patients with AHF, and its prognostic value
      is maintained beyond that provided by other well-established risk factors or
      biomarkers.

PMID- 30276662
TI  - Myocyte Enhancer Factor 2c Regulates Dendritic Complexity and Connectivity of
      Cerebellar Purkinje Cells.
AB  - Mef2c haploinsufficiency is implicated in behavioral deficits related to autism,
      schizophrenia, and intellectual disability. Although perturbations in the
      cerebellum, notably Purkinje cells, have been linked to these neurological
      disorders, the underlying mechanisms remain poorly understood. In this study, we
      investigated the roles of Mef2c in cerebellar Purkinje cells during the first
      three weeks of postnatal development. Our analysis revealed that in comparison to
      other members of the Mef2 family, Mef2c expression is limited to postnatal
      Purkinje cells. Because the role of Mef2c has not been assessed in GABAergic
      neurons, we set out to determine the functional significance of Mef2c by knocking
      down the expression of Mef2c selectively in Purkinje cells. We found that the
      loss of Mef2c expression during the first and second postnatal week results in an
      increase in dendritic arborization without impact on the general growth and
      migration of Purkinje cells. The influence of Mef2c on dendritic arborization
      persists throughout the first three weeks, but is most prominent during the first
      postnatal week suggesting a critical period of Mef2c activity. Additionally, the
      loss of Mef2c expression results in an increase in the number of spines
      accompanied by an increase in Gad67 and vGluT1 puncta and decrease in vGluT2
      puncta. Thus, our results reveal the specific expression and functional relevance
      of Mef2c in developing Purkinje cells and offer insight to how disruption of the
      expression of Mef2c in a GABAergic neuronal subtype may lead to pathogenesis of
      cerebellar-associated disorders.

PMID- 30276663
TI  - Evidence Supporting a Role for the Blood-Cerebrospinal Fluid Barrier Transporting
      Circulating Ghrelin into the Brain.
AB  - The stomach-derived hormone ghrelin mainly acts in the brain. Studies in mice
      have shown that the accessibility of ghrelin into the brain is limited and that
      it mainly takes place in some circumventricular organs, such as the median
      eminence. Notably, some known brain targets of ghrelin are distantly located from
      the circumventricular organs. Thus, we hypothesized that ghrelin could also
      access the brain via the blood-cerebrospinal fluid (CSF) barrier, which consists
      of the choroid plexus and the hypothalamic tanycytes. Using systemic injection of
      ghrelin or fluorescent-ghrelin in mice, we found that cells of the blood-CSF
      barrier internalize these molecules. In time-response studies, we found that
      peripherally injected fluorescent-ghrelin quickly reaches hypothalamic regions
      located in apposition to the median eminence and more slowly reaches the
      periventricular hypothalamic parenchyma, adjacent to the dorsal part of the third
      ventricle. Additionally, we found that CSF ghrelin levels increase after the
      systemic administration of ghrelin, and that central infusions of either an anti
      ghrelin antibody, which immuno-neutralizes CSF ghrelin, or a scrambled version of
      ghrelin, which is also internalized by cells of the blood-CSF barrier, partially
      impair the orexigenic effect of peripherally injected ghrelin. Thus, current
      evidence suggests that the blood-CSF barrier can transport circulating ghrelin
      into the brain, and that the access of ghrelin into the CSF is required for its
      full orexigenic effect.

PMID- 30276664
TI  - A Life Course Perspective on the Ways Older Men and Women Discuss Sexual Issues.
AB  - The present study examined how older adults communicate about sexual issues in
      light of the tremendous societal changes that have taken place with regard to
      sexuality in the past few decades. We relied on interviews with 47 Israelis 60
      years of age and older who were instructed to discuss sexuality in old age and
      its unique characteristics, using semi-structured interviews. Analysis consisted
      of repeated comparisons and contrasts to identify common themes. A common thread
      of "secrets and lies" characterized the discussion of sexual issues throughout
      the life course of respondents. The findings showed that although older adults
      have been aware of the limited information provided to them during their
      upbringing and of the limited room allowed to sexuality in their emerging
      adulthood years, many have continued to find it difficult to address sexual
      issues, even in later life. Moreover, many perceived the information currently
      available about sexuality and the contemporary approach to sexuality brought by
      the media or their children and grandchildren as being somewhat inadequate.
      Implications for practice are discussed.

PMID- 30276665
TI  - Cochlear hair cell densities in the rabbit.
AB  - A typical cochleogram was plotted to investigate hair cell densities as a
      percentage along the whole length of the basilar membrane (BM) of the rabbit, the
      length of the BM and the width of the organ of Corti. We generated surface
      preparations of cochlea from adult, healthy New Zealand White (NZW) rabbits. The
      numbers of inner hair cells (IHCs) and outer hair cells (OHCs) were counted from
      images acquired from a digital camera attached to an Olympus light microscope
      with a scale of 100 MUm as a primary unit drawn continuously, and the numbers of
      IHCs and OHCs were converted to densities at 10% intervals along the length of
      the cochlea. Meanwhile, the length of the BM and the width of the organ of Corti
      were calculated. The average length of the cochlea was 14.504 +/- 0.403 mm, while
      the total number of IHCs and the numbers of OHCs in the first, second, and third
      rows were 1556 +/- 13, 1840 +/- 47, 1842 +/- 46, and 1840 +/- 45, respectively,
      accounting for 21.98%, 26.00%, 26.02%, and 26.00% of the total number of cells,
      respectively. The densities of each row of OHCs reported in 10% intervals were
      greater than the densities of the IHCs corresponding to their anatomical
      locations within the cochlea. The densities of OHCs in each row were distributed
      uniformly along the BM, while the IHCs densities were not and showed a bimodal
      distribution with a maximum density at the apex and at 70-80% of the cochlear
      length from the apex but a lower density in the remaining cochlea. The width of
      the organ of Corti decreased successively from the apex to the base.

PMID- 30276666
TI  - Formulation and evaluation of carrier-free dry powder inhaler containing
      sildenafil.
AB  - Pulmonary delivery of sildenafil for the treatment of pulmonary arterial
      hypertension could overcome the limitations of intravenous and oral
      administration routes, such as poor patient compliance and systemic side effects.
      In this study, a carrier-free dry powder inhaler (DPI) formulation was developed,
      using spray drying technique and L-leucine as a dispersibility enhancer.
      Sildenafil citrate salt and sildenafil free base were evaluated for drug
      transport using a Calu-3 cell model, and their suitability for DPI production by
      spray drying was tested. Characteristics of the resultant carrier-free DPI
      powders were examined, namely crystallinity, morphology, size distribution,
      density, zeta potential, and aerodynamic performance. A Box-Behnken design was
      adopted to optimize the formulation and process conditions, including leucine
      amount, fraction of methanol in spraying solvent, and inlet temperature. While
      both sildenafil forms exhibited sufficient permeability for lung absorption, only
      sildenafil base resulted in DPI powders which were stable for 6 months. The
      introduction of leucine into the formulations effectively enhanced aerodynamic
      performance of the powders and particles with favorable size, shape, and density
      were produced. The optimal DPI formulation determined from experimental design
      possesses excellent aerodynamic performance with 89.39% emitted dose and 80.08%
      fine particle fraction, indicating the possibility of incorporating sildenafil
      into carrier-free DPIs for pulmonary delivery.

PMID- 30276667
TI  - Promises and Pitfalls of Using Digital Traces for Demographic Research.
AB  - The digital traces that we leave online are increasingly fruitful sources of data
      for social scientists, including those interested in demographic research. The
      collection and use of digital data also presents numerous statistical,
      computational, and ethical challenges, motivating the development of new research
      approaches to address these burgeoning issues. In this article, we argue that
      researchers with formal training in demography-those who have a history of
      developing innovative approaches to using challenging data-are well positioned to
      contribute to this area of work. We discuss the benefits and challenges of using
      digital trace data for social and demographic research, and we review examples of
      current demographic literature that creatively use digital trace data to study
      processes related to fertility, mortality, and migration. Focusing on Facebook
      data for advertisers-a novel "digital census" that has largely been untapped by
      demographers-we provide illustrative and empirical examples of how demographic
      researchers can manage issues such as bias and representation when using digital
      trace data. We conclude by offering our perspective on the road ahead regarding
      demography and its role in the data revolution.

PMID- 30276669
TI  - Should the use of neck-ultrasonography be reduced during the follow-up of
      differentiated thyroid cancer patients with undetectable or low (i.e., < 1 ug/L)
      thyroglobulin levels and negative thyroglobulin antibody?

PMID- 30276668
TI  - Computed tomography coronary angiography in patients without known coronary
      artery disease can demonstrate possible non-cardiovascular causes of non-acute
      retrosternal chest pain.
AB  - OBJECTIVES: To assess the computed tomography coronary angiography (CTCA)
      accuracy for demonstrating possible non-cardiovascular causes of non-acute
      retrosternal chest pain in patients without known coronary artery disease (CAD)
      and to correlate CTCA results with the patient management and relief from pain.
      METHODS: This prospective observational study was approved by the ethical
      committee. Consecutive patients suffering non-acute chest pain who underwent CTCA
      and with not known CAD were enrolled and classified as having coronary diseases
      (CD) or extracardiac diseases (ECD). Association between age, sex, body mass
      index (BMI), cardiovascular risk factors, and type of chest pain with CD or ECD
      was estimated. Correlation between BMI classes and each risk factor was also
      calculated. RESULTS: A total of 106 patients (60 males; age 62 +/- 14 years [mean
      +/- standard deviation]; mean BMI 27) were enrolled. Hypertension was found in
      71/106 (67%); smoking was significantly more frequent among males (p = 0.003) and
      hypercholesterolemia among females (p = 0.017); hypertension and
      hypercholesterolemia significantly correlated with age, and hypertension also
      with BMI. Pain was atypical in 70/106 (66%) patients. The kind of pain did not
      correlate with disease or gender. CTCA showed possible causes of chest pain in
      69/106 (65%) patients; 32/69 (47%) having only CD, 23/69 (33%) only ECD, and
      14/69 (20%) both CD and ECD. Prevalence was: hiatal hernia 35/106 (33%);
      significant CAD 24/106 (23%); myocardial bridging 22/106 (21%). At follow-up of
      94/106 (89%) patients, 71/94 (76%) were pain-free, 14/17 (82%) significant CAD
      had been treated, and only one patient with non-significant CAD was treated after
      CTCA. CONCLUSION: CTCA suggested possible causes of non-acute pain in 65% of
      patients. MAIN MESSAGES: * CTCA can either rule in or rule out possible causes of
      chest pain alternative to CAD. * Clinically relevant findings were detected in
      65% of patients with non-acute chest pain. * Non-cardiovascular diseases
      potentially explained symptoms in 35% of patients.

PMID- 30276670
TI  - Clinical and genetic characteristics of familial hypercholesterolemia patients
      with type 2 diabetes.
AB  - PURPOSE: Though type 2 diabetes mellitus (T2DM) is an important and independent
      risk factor for coronary artery disease (CAD) in the general population, the
      impact of T2DM on CAD in patients with familial hypercholesterolemia (FH) is less
      understood. Thus, the current study aimed to examine the features of FH patients
      with T2DM and explore the effects of T2DM on CAD in FH. METHODS: A total of 289
      clinical heterozygous FH (HeFH) patients diagnosed with Dutch Lipid Clinic
      Criteria were consecutively recruited and divided into a T2DM group (n = 58) and
      non-T2DM group (n = 231). Clinical characteristics and laboratory findings were
      compared between the two groups. Target exome sequencing was used for gene
      mutation analysis. RESULTS: HeFH patients with T2DM had significantly higher
      levels of triglycerides, body mass index and free fatty acids than did non-T2DM
      patients; moreover, patients with T2DM more frequently exhibited hypertension.
      However, the spectrum of FH-causing mutations was not significantly different (p
      = 0.061). Notably, patients with T2DM had higher prevalence of CAD (p = 0.012)
      and higher Gensini Score (p = 0.002). The regression analysis confirmed that
      HbA1c was an independent risk factor for both the presence and severity of CAD
      [OR 2.321 (1.098-4.904), p = 0.027; OR 1.349 (1.032-1.762), p = 0.028,
      respectively] in patients with HeFH. CONCLUSIONS: Although there were not many
      differences in the clinical, lipid and genetic aspects of HeFH patients with and
      without T2DM, T2DM and HbA1c were associated with worse coronary lesions,
      suggesting that diabetes and the degree of blood glucose control are also
      important determinants of cardiovascular disease in these patients.

PMID- 30276671
TI  - Lessons learned from a student-driven initiative to design and implement an Organ
      and Tissue Donation course across Canadian medical schools.
AB  - The competencies required of the well-trained physician are constantly evolving,
      and medical education must adapt accordingly. In response, a growing number of
      influential medical education licensing and accreditation bodies have proposed
      frameworks that outline society's expectations of physician competencies. In
      Canada, undergraduate and graduate curricula have undergone major changes to meet
      the specifications of the CanMEDS framework, and similar efforts are underway
      internationally. Nonetheless, ensuring the values enshrined within such
      frameworks become integral to a physician's identity remains challenging. We
      believe that student-led curricular initiatives represent a novel way of
      approaching this shifting medical education landscape.In this article, we reflect
      on lessons we learned as medical students spearheading an initiative to change
      how organ and tissue donation is taught in Canadian medical schools. Citing
      relevant medical education literature where applicable, we include a detailed
      description of our approach as a roadmap for students contemplating their own
      curricular innovations. By outlining the factors influencing this project's
      implementation, as well as the benefits and limitations of student participation
      in curriculum reform, we offer educators a fresh perspective on optimizing the
      student role in this important process. Ultimately, the authors argue that not
      only can student participation render curricular content more accessible to
      learners, but that the responsibilities students take on in this role naturally
      lead to the development of CanMEDs-based competencies such as advocacy,
      scholarship, and inter-professionalism.

PMID- 30276672
TI  - How accurate and precise are CT based measurements of iodine concentration? A
      comparison of the minimum detectable concentration difference among single source
      and dual source dual energy CT in a phantom study.
AB  - OBJECTIVES: To assess the impact of scan- and patient-related factors on the
      error and the minimum detectable difference in iodine concentration among
      different generations of single-source (SS) fast kV-switching and dual-source
      (DS) dual-energy CT (DECT). METHODS: Lesions having eight different iodine
      concentrations (0.2-4 mgI/mL) were emulated in a 3D-printed phantom of medium and
      large size. Each combination of concentration and size was scanned in dual-energy
      mode on four different SS and DS DECTs. Radiation doses were 7 and 10 mGy (medium
      size) and 10, 13, and 16 mGy (large size). Iodine maps were reconstructed with
      filtered back projection (FBP) and vendor-specific iterative reconstruction
      algorithms (IRs). Absolute error of iodine quantification (E) was measured.
      Multivariate regression models determined the influence of CT scanner, iodine
      concentration, phantom size, radiation dose, and reconstruction algorithm on E.
      The minimum detectable difference in iodine concentration (ICmin) under the same
      imaging conditions (intra-conditional) and among different imaging conditions
      (inter-conditional) was calculated. RESULTS: The error was significantly lower in
      current than in previous DECT generations (p < 0.001). For all CT scanner
      conditions, the error was significantly higher with increasing phantom size and
      decreasing radiation dose (p < 0.001). Iodine concentration only significantly
      affected the error for SS DECT (p < 0.001). ICmin depended on patient- and scan
      related factors and ranged from 0.4 to 1.5 mgI/mL. CONCLUSIONS: Patient- and scan
      related factors have a significant impact on the error and minimum detectable
      difference in iodine concentration within and among SS fast kV-switching and DS
      DECT. KEY POINTS: * Patient- and scan-related factors have a significant impact
      on the error and minimum detectable difference in dual-energy CT-based iodine
      quantification. * Third-generation DECTs outperformed second-generation scanners
      for both single-source and dual-source dual-energy CT. * The minimum intra- and
      inter-conditional detectable difference in iodine concentration ranged from 0.4
      to 1.5 mg iodine/mL.

PMID- 30276673
TI  - Quantitative susceptibility mapping in the human fetus to measure blood
      oxygenation in the superior sagittal sinus.
AB  - OBJECTIVES: To present the feasibility of performing quantitative susceptibility
      mapping (QSM) in the human fetus to evaluate the oxygenation (SvO2) of cerebral
      venous blood in vivo. METHODS: Susceptibility weighted imaging (SWI) data were
      acquired from healthy pregnant subjects (n = 21, median = 31.3 weeks,
      interquartile range = 8.8 weeks). The susceptibility maps were generated from the
      SWI-phase images using a modified QSM processing pipeline, optimised for fetal
      applications. The processing pipeline is as follows: (1) mild high-pass filtering
      followed by quadratic fitting of the phase images to eliminate background phase
      variations; (2) manual creation of a fetal brain mask that includes the superior
      sagittal sinus (SSS); (3) inverse filtering of the resultant masked phase images
      using a truncated k-space approach with geometric constraint. Further, the
      magnetic susceptibility, ?chiv and corresponding putative SvO2 of the SSS were
      quantified from the generated susceptibility maps. Systematic error in the
      measured SvO2 due to the modified pipeline was also studied through simulations.
      RESULTS: Simulations showed that the systematic error in SvO2 when using a mask
      that includes a minimum of 5 voxels around the SSS and five slices remains < 3%
      for different orientations of the vessel relative to the main magnetic field. The
      average ?chiv in the SSS quantified across all gestations was 0.42 +/- 0.03 ppm.
      Based on ?chiv, the average putative SvO2 in the SSS across all fetuses was 67%
      +/- 7%, which is in good agreement with published studies. CONCLUSIONS: This in
      vivo study demonstrates the feasibility of using QSM in the human fetal brain to
      estimate ?chiv and SvO2. KEY POINTS: * A modified quantitative susceptibility
      mapping (QSM) processing pipeline is tested and presented for the human fetus. *
      QSM is feasible in the human fetus for measuring magnetic susceptibility and
      oxygenation of venous blood in vivo. * Blood magnetic susceptibility values from
      MR susceptometry and QSM agree with each other in the human fetus.

PMID- 30276674
TI  - Absence of potential gadolinium toxicity symptoms following 22,897 gadoteric acid
      (Dotarem(r)) examinations, including 3,209 performed on renally insufficient
      individuals.
AB  - OBJECTIVES: Recent safety concerns regarding gadolinium-based contrast agents
      (GdCAs) concluded with the suspension of some agents from the European market,
      yet a clinical consequence remains unknown. We used electronic health records to
      investigate the incidence of potential toxicity to gadoteric acid (Dotarem(r))
      within our local population, including those with renal insufficiency (RI).
      METHODS: Data for patients who underwent contrast-enhanced MRI were identified,
      stratified by renal function at time of scan and retrospectively followed using
      routinely collected health data. Searches performed were: records of
      hypersensitivity reactions; diagnoses of nephrogenic systemic fibrosis (NSF);
      onset of chronic pain, a symptom that has been associated with NSF and the
      theorised gadolinium deposition disease (GDD); and post-contrast acute kidney
      injury (PC-AKI). Comparisons were made between patients and controls (those who
      underwent non-contrast scans) via chi-square and ANOVA statistical tests.
      RESULTS: Of the 22,897 contrast-enhanced MRI scans performed locally from 2004
      2016 (adult, n = 22,325 and paediatric, n = 572), 14% were performed on patients
      with RI (30 <= eGFR < 60, n = 2,622; 15 <= eGFR < 30, n = 464; eGFR < 15, n =
      123). Two adult patients (0.01%) suffered hypersensitivity reactions. Zero cases
      of NSF were reported, with an average follow-up time of 6.0 +/- 2.5 years (range,
      8 months-15 years). Analysis failed to highlight statistically higher rates of
      chronic pain onset post-MRI (adult: p = 0.777, paediatric: p = 0.578), or PC-AKI
      (adult: p = 0.566, paediatric: p = 0.841), in the patient groups compared to
      controls. CONCLUSIONS: These data indicate that administration of gadoteric acid
      to RI patients does not result in a higher rate of signs or symptoms that may be
      associated with gadolinium toxicity when compared to controls. KEY POINTS: *
      Following 22,897 administrations of gadoteric acid to a local population, there
      was no association with symptoms that may be associated with gadolinium toxicity.
      * Zero cases of nephrogenic systemic fibrosis were reported following 3,209
      gadoteric acid administrations to a cohort of renally insufficient patients. * A
      low number of hypersensitivity reactions were observed (0.01%) and no higher rate
      of chronic pain or post-contrast acute kidney injury were noted when compared
      with a control cohort of non-contrast-enhanced examinations.

PMID- 30276675
TI  - The value of post-mortem computed tomography of burned victims in a forensic
      setting.
AB  - OBJECTIVES: Fire deaths are challenging fatalities for forensic pathologists, as
      the main question of whether death was due to the fire or not needs to be
      answered. In this retrospective study, we assessed whether post-mortem computed
      tomography (PMCT) has an added value prior to a forensic autopsy of burned
      victims. METHODS: From 2008 to 2016, a PMCT was performed in 50 burned corpses
      prior to a complete forensic autopsy. In retrospect, all 50 PMCT scans were
      systematically assessed by a forensically experienced radiologist, masked from
      the autopsy reports. Subsequently, the PMCT findings were compared with the
      autopsy reports. RESULTS: Heat fractures, contractions and destruction of
      extremities, subcutaneous emphysema and post-mortem gas collections were easier
      to detect by PMCT compared to autopsy. Alterations by penetrating and blunt
      trauma and the presence of foreign bodies were easy to detect by PMCT as well by
      autopsy. PMCT was, however, not successful in detecting signs of vitality during
      the fire, detection of superficial thermal injuries and to answer the main
      question of the forensic autopsy, which is to investigate the cause of death.
      CONCLUSIONS: PMCT prior to autopsy is a valuable add-on in the post-mortem
      forensic investigation of burned victims for detection of hidden signs of trauma,
      gas collections and foreign bodies. However, since PMCT cannot answer the two
      main questions in forensic examination-determining the cause of death and
      detecting signs of vitality during the fire-it cannot replace an autopsy. KEY
      POINTS: * Post-mortem CT (PMCT) in burned victims shows hidden signs of trauma. *
      Foreign bodies and gas collections can easily be detected. * Cause of death and
      vitality signs cannot be assessed by PMCT.

PMID- 30276676
TI  - Microvascular characteristics of lower-grade diffuse gliomas: investigating
      vessel size imaging for differentiating grades and subtypes.
AB  - OBJECTIVES: Vessel size imaging (VSI) could reveal average microvessel diameter.
      The aim was to investigate microvascular characteristics and the efficacy of VSI
      in lower-grade glioma (LGG) grading and subtype differentiation based on 2016
      classification of central nervous system tumours. METHODS: Fifty-seven LGG (grade
      II/III, 36/21) patients who received VSI examination before surgery were
      retrospectively analysed. The average (Rmean) and maximum (Rmax) vessel size
      indexes were obtained. The long (VDmax) and short (VDmin) vascular diameter,
      microvascular area (MVA) and density (MVD) were obtained using paraffin
      specimens. The patients were divided into grades II and III, and histological and
      molecular subtypes. The differences among microvascular parameters of different
      subtypes and grades were compared. Two-sample t-test, analysis of variance test,
      Mann-Whitney test, the Kruskal-Wallis test and Pearson correlation analysis were
      used for statistics. RESULTS: Rmean, Rmax, VDmin, VDmax, and MVA were higher in
      grade-III than in grade-II LGGs (p < 0.05) in each type except the isocitrate
      dehydrogenase (IDH) mutant with 1p/19q-intact type. For grade II, the IDH mutant
      with 1p/19q co-deleted and IDH wildtype possessed more dominant angiogenesis than
      IDH mutant with 1p/19q-intact type, revealed by lower Rmean, Rmax and VDmin while
      higher MVD for the former (p < 0.05), the same as oligodendroglioma versus
      astrocytoma. Rmean and Rmax correlated with VDmin (r = 0.804, 0.815, p < 0.05),
      VDmax (r = 0.766, 0.774, p < 0.05) and MVA (r = 0.755, 0.759, p < 0.05),
      respectively, while they had no correlation with MVD (r = -0.085, -0.080, p >
      0.05). CONCLUSIONS: VSI holds great potential for non-invasively revealing
      microvascular characteristics of LGGs pre-surgery and differentiating their
      grades and molecular subtypes. KEY POINTS: * VSI can assist in differentiating
      grade-II and -III gliomas. * The IDH gene and 1p/19q chromosome may influence the
      angiogenesis in grade-II gliomas. * VSI is valuable for differentiating the
      molecular subtypes of grade-II gliomas.

PMID- 30276677
TI  - Enhanced expression of nidogen 1 around the nest of basal cell carcinoma compared
      with that around squamous cell carcinoma.
AB  - Basal cell carcinoma (BCC) is a malignant skin tumor originating from cells of
      the epidermal basal layer and adnexal epithelium, especially in sun-exposed
      areas. Unlike squamous cell carcinoma (SCC), BCC has a propensity to grow only
      locally possibly due to differences in the surrounding microenvironment including
      the basement membrane (BM) and stroma. To investigate the components constituting
      the BM and surrounding connective tissue in BCC and SCC, we analyzed the
      expression of BM proteins, nidogen 1 (NID1) and type IV collagen (COL4). We
      compared the immunohistochemical expressions of NID1 and COL4 among tumor
      specimens from BCC, SCC and its precancerous condition, actinic keratosis (AK),
      (n = 5 each condition). The expressions of NID1 and COL4 were both decreased
      around the tumor nest of SCC. In contrast, the expressions of both NID1 and COL4
      around the nest of BCC were much higher than in the peri-lesional normal skin not
      only at the BM, but also in the surrounding stromal tissue. Our findings imply
      that the surrounding stromal cells of BCC, but not SCC or AK, excessively produce
      NID1 and COL4, which may be involved in preventing BCC cells from destroying the
      BM and invading the dermis.

PMID- 30276678
TI  - [Surgical refixation of gluteal tendon tears by mini-open double-row technique].
AB  - OBJECTIVE: Stable refixation of gluteal tendons at the anatomic footprint by
      large-area contact by the means of knotless double-row anchor fixation (HipBridge
      technique). INDICATIONS: Symptomatic tear of gluteus medius and/or gluteus
      minimus tendon with persisting pain after nonsurgical treatment, or primarily
      reconstructable mass rupture with gluteal insufficiency, revision surgeries.
      CONTRAINDICATIONS: Primary nonreconstructable mass ruptures, atrophic or fatty
      degeneration of gluteal muscles grade Goutallier 4, local infections. SURGICAL
      TECHNIQUE: Lateral position, longitudinal skin incision over greater trochanter,
      longitudinal incision of iliotibial band, resection of trochanteric subgluteus
      maximus bursa, longitudinal splitting of gluteal tendons over tear, debridement
      and mobilisation of tendons for sufficient distalisation to tendon footprint at
      anterior and lateral trochanteric facet, debridement of sclerotic greater
      trochanter, punching and tapping of proximal row, placement of two proximal
      anchors loaded with nonresorbable suture tape, fan-shaped four times gluteal
      tendon perforation at myotendinous transition zone, double-V-shape crossing of
      suture tapes, punching and tapping of distal row, fixation of crossed tapes with
      two distal knotless suture anchors under mild pretensioning of gluteal tendons,
      side-to-side tendon suture, vastogluteal and iliotibial band closure, wound
      closure. POSTOPERATIVE MANAGEMENT: Stage-dependent physiotherapy with partial
      weight-bearing with 20 kg for 6 weeks, no active abduction, no adduction and no
      external rotation in flexion for 6 weeks after surgery. From week 7 after
      surgery, free range of motion, active-assisted abduction and increase in weight
      bearing by 15 kg/week. No peak load for 4 months. Thromboembolic prophylaxis
      until full weight-bearing is reached. RESULTS: Success rates of 80-90% can be
      expected in cases with no or only minor muscle atrophy.

PMID- 30276679
TI  - Analysis of methanogens adsorption and biogas production characteristics from
      different coal surfaces.
AB  - The aim of this study was to examine the biogas production and the adsorption
      aspect of microorganism from different coals. Coal samples were obtained from
      Qianqiu mine and Guandi mine. Microbial populations were cultured from the coal
      mine drainage. After an anaerobic reaction period at about 35  degrees C,
      adsorption rate was determined by the spectrophotometer, while a scanning
      electron microscopy was used to observe the microorganisms on the coal and the
      headspace methane was analyzed using gas chromatography. Results show that the
      coal rank and particle size serve as important factors influencing the adsorption
      of microorganism and biogenic methane production. With decreasing particle size,
      the Qianqiu coal produced a considerable adsorption rate between 75 and 79%,
      while the adsorption rate of Guandi coal was between 52 and 74%. Meanwhile, the
      density of microorganisms from the Qianqiu coal surface demonstrated a higher
      level of adsorption than that of Guandi coal following the scanning electron
      microscopy images. Additionally, Qianqiu coal produced a higher level of biogas
      production (391.766-629.199 MUmol/g) than that of Guandi coal (292.835-393.744
      MUmol/g) and the Qianqiu coal also generated a higher concentration of methane
      during the incubation. When the adsorption rate decreasing, the biogas production
      from various pulverized coals appeared to be decreased and demonstrated a
      positive correlation to the adsorption rate. The results of this study suggest
      that the adsorption behavior of microorganisms is closely related to the effect
      of coal biodegradation and contributes to the biogenic methane production
      potential.

PMID- 30276681
TI  - Testing the role of tourism development in ecological footprint quality: evidence
      from top 10 tourist destinations.
AB  - The aim of this study is to search the role of tourism development in the
      environmental quality for the major tourist destination countries. Ecological
      footprint has been selected as a proxy of environmental quality with this respect
      while top 10 tourist countries have been selected as samples of the study. Panel
      estimation results of this study show that the tourism-induced environmental
      Kuznets curve has been confirmed for these tourist countries which has an
      inverted U-shape. Tourism development in the selected countries exerts negatively
      significant effects on the levels of ecological footprints. Thus, this study
      concludes that tourism development in top tourist countries exert improving
      effect on the levels of environmental quality.

PMID- 30276682
TI  - Transformation of the chemical composition of surface waters in the area of the
      exploited Lomonosov diamond deposit (NW Russia).
AB  - The specific objective of this study was to investigate the changes in the
      chemical composition of river waters during the exploitation of the Lomonosov
      diamond deposit and the danger of these changes for the ichthyofauna. It was
      found that the Ca-HCO3 composition of river water both upstream and downstream
      from the quarry was almost identical before discharge of the drainage waters into
      the river. In subsequent years, the water downstream from the quarry acquired a
      Na-HCO3 composition, and then a Na-HCO3-Cl composition and TDS increased by 2.5
      times. With respect to Fe, Mn, and Mo, concentrations that are above the maximum
      permissible concentrations (MPCs) for fishery rivers are apparent. At the same
      time, elevated Fe and Mn concentrations are associated with the natural
      composition of river water. The negative influence of drainage waters is
      manifested only with respect to the high concentrations of Mo. An important role
      in increasing Mo concentrations in drainage waters is played by the processes of
      hydrolysis of sodium aluminosilicates and mixing of fresh water with salt water.
      The concentrations of Sr, B, Ba, V, and Cr in drainage waters are higher than
      those in surface waters. However, they generally do not exceed the concentrations
      of the current MPCs. The source of Cr, Ba, Ni, and V in the drainage waters can
      be the products of the kimberlite magmatism. The possible impacts of metals
      effects on fish are presented.

PMID- 30276680
TI  - Oxidative stress, energy metabolism and molecular responses of earthworms
      (Eisenia fetida) exposed to low-density polyethylene microplastics.
AB  - Soils are both a sink and a pathway of plastic wastes, but there is a great lack
      of knowledge regarding their impacts on soil biota. To tackle the mechanisms of
      toxicity of these contaminants to soil invertebrates, earthworms (Eisenia fetida
      Savigny, 1826) were exposed during 28 days to different concentrations of low
      density polyethylene microplastics (62, 125, 250, 500 and 1000 mg MPs kg-1
      soildw) with sizes ranging between 250 and 1000 MUm, in an artificial soil. The
      ecotoxicological responses were evaluated by analysing various oxidative stress
      biomarkers (catalase, glutathione S-transferase and thiobarbituric acid reactive
      substances), a biomarker of energy metabolism (lactate dehydrogenase) and overall
      organism molecular changes by Fourier transform infrared spectrometry (FTIR) and
      nuclear magnetic resonance (NMR) analyses. Significant effects resulting from an
      unbalanced oxidative stress system, expressed in terms of thiobarbituric acid
      reactive substances levels were recorded on earthworms exposed at the three
      highest concentrations tested. Despite that, no significant changes were recorded
      on the molecular profiles of earthworms by FTIR-ATR. NMR analysis pointed out for
      differences from the control, only for earthworms exposed to the lowest
      concentration of MPs. Considering that stress responses are complex, and involve
      multiple mechanisms, a cluster analysis taking into account all the parameters
      assessed, clearly identified two groups of earthworms separated by the
      concentration of 250 mg MPs kg-1 soildw, above each meaningful effects were
      recorded.

PMID- 30276683
TI  - Ultrasonic seed treatment improved physiological and yield traits of rice under
      lead toxicity.
AB  - Lead (Pb) is a highly toxic metal that damages normal plant metabolism and often
      results in reduced crop growth and yield. To measure whether or not ultrasonic
      seed (US) treatment alleviates Pb stress in rice, the seeds of two rice
      cultivars, i.e., Guangyan1 and Huahang31, were exposed to 30 min of ultrasonic
      vibration and then the seedlings were transplanted to Pb-contaminated soil.
      Results revealed that the Pb contents in roots, stems, leaves, panicles (at
      heading), and brown rice (at maturity) were lower in US treatment than control
      (CK; without US treatment); the trend for accumulation of Pb in different plant
      parts was recorded as: root ? stems ? leaves ? panicles ? brown rice in both rice
      cultivars. Overall, the Pb contents in the brown rice of Huahang31 were higher
      than those in Guangyan1. Moreover, the contents of proline and soluble protein as
      well as the activities of superoxide dismutase (SOD), catalase (CAT), and
      ascorbate peroxidase (APX) were significantly higher while the malondialdehyde
      (MDA) contents were significantly reduced in US treatment compared to CK. The
      effective panicle number, seed set percentage, grains per panicle, 1000-grain
      weight, and grain yield were increased by 8.9%, 5.3%, 6.8%, 4.4%, and 26.6% in
      Guangyan1 and 3.2%, 5.7%, 5.7%, 5.0%, and 24.2% in Huahang31, respectively in US
      treatment compared to CK. Hence, seed treatment with ultrasonic waves could
      improve rice performance and reduce brown rice Pb accumulation under Pb-polluted
      soils.

PMID- 30276684
TI  - Protective potential of Opuntia microdasys flower decoction on fructose-alloxan
      induced diabetic rats on kidney and pancreas: chemical and immunohistochemical
      analyses.
AB  - Diabetes is a serious condition that is linked to the development of oxidative
      stress causing among many other effects, kidney failure and pancreatic disorders.
      However, traditional plant-based remedies can be considered an alternative to
      diabetes healing. In this context, this study was oriented towards evaluating the
      protective effect of the flowers of Opuntia microdasys Lehm. collected in Tunisia
      at a biochemical and histological level on kidneys and pancreas of a type 2
      diabetic rats. Renal and pancreatic toxicities were induced in diabetic male
      Wistar rats by fructose alloxan. Diabetic rats were treated with an extract
      obtained from flowers collected at post-flowering stage (OFP) (100 and 200 mg kg
      1 bw) and metformin (100 mg kg-1 bw) for 28 days. Oral administration of OFP at
      200 mg kg-1 bw showed significant reduction of the uric acid, urea, creatinine,
      amylase, lipase, and glycated hemoglobin (HbAlc). The levels of SOD, CAT, and GPx
      were increased, while protein carbonyls and lipid peroxidation TBARS levels were
      reduced in the kidney and pancreas. The altered kidney and pancreas histology
      were restored in rats treated with OFP. Thus, the present study demonstrated that
      OFP has antihyperglycemic activity in fructose-alloxan-induced diabetic rats.

PMID- 30276686
TI  - Response of Tradescantia plants to oxidative stress induced by heavy metal
      pollution of soils from industrial areas.
AB  - Numerous investigations have demonstrated that even soil in which concentrations
      of individual elements do not exceed permissible limits can cause harmful effects
      in living organisms. In the present study, polluted-soil-induced oxidative stress
      was evaluated using Tradescantia clone 4430, which is widely used for
      genotoxicity evaluations, employing biochemical (superoxide dismutase (SOD),
      contents of ascorbic acid (AA), carotenoids (Car), hydrogen peroxide (H2O2),
      chlorophyll (Chl) a/b ratio), and molecular (RAPD and differential display (DD
      PCR)) markers after long-term exposure. The activity (staining intensity) of SOD
      isoforms in Tradescantia leaves was higher in plants grown in all heavy-metal
      polluted test soils compared to the control. No direct link between the soil
      pollution category and the contents of AA, Car, Chl a/b in Tradescantia leaves
      was revealed, but the concentration of H2O2 was shown to be a sensitive
      biochemical indicator that may appropriately reflect the soil contamination
      level. Both short-term (treatment of cuttings with H2O extracts of soil) and long
      term (0.5 and 1.0 year) exposure increased MN frequencies, but the coincidence of
      the MN induction and the soil pollution level was observed only in some cases of
      long-term exposure. Soil (geno)toxin-induced polymorphism in the RAPD profile was
      determined with two primers in plants after long-term exposure to soils of an
      extremely hazard category. Transcript profiling of plants after long-term
      cultivation in test soils using DD-PCR showed that the majority of differentially
      expressed transcript-derived fragments (TDFs) were homologous to genes directly
      or indirectly participating in photosynthesis, the abiotic stress response, and
      signal transduction cascades.

PMID- 30276685
TI  - Differential transcriptional changes in human alveolar epithelial A549 cells
      exposed to airborne PM2.5 collected from Shanghai, China.
AB  - Fine particulate matters (PM2.5) are the core pollutants of haze episode, which
      pose a serious threat to the human health of developing countries. However, the
      mechanisms involved in PM2.5-induced hazard influence are not to fully
      elucidated. In the present study, human lung epithelial cells (A549) were exposed
      to various concentrations of PM2.5 samples collected from Shanghai, China.
      Illumina RNA-Seq method with transcriptome, Gene Ontology (GO), and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were further
      employed to identify the detrimental effects of PM2.5 on A549 cells in vitro. A
      total of 712 differentially expressed genes were obtained from global
      transcriptome profiling of A549 cells after PM2.5 exposure. In addition, GO
      function enrichment analysis revealed that major differentially expressed genes
      (DEGs) involved in the biological process of the immune system and the response
      to the stress. KEGG pathway analysis further proposes that infectious disease,
      cancers, cardiovascular disease, and immune disease pathway were the key human
      disease events that occur in A549 cells under PM2.5 stress. The data obtained
      here shed light on the related biological process and gene signaling pathways
      affected by PM2.5 exposure. This study aids our understanding of the complicated
      mechanisms related to PM2.5-induced health effects and is informative for the
      prevention and treatment of PM2.5-induced systemic diseases.

PMID- 30276687
TI  - Morphophysiological variation and metal concentration in the thallus of
      Parmotrema tinctorum (Despr. ex Nyl.) Hale between urban and forest areas in the
      subtropical region of Brazil.
AB  - Anthropic activities such as the emission of pollutants resulting from industrial
      and agropastoral activities promote several changes in urban and forest areas.
      Lichens are organisms that are used in air quality evaluations due to their
      sensitivity to these changes. The aim of this study is to analyze the presence of
      morphophysiological damages and the metal concentration in samples of the lichen
      Parmotrema tinctorum, in urban and forest areas, checking for possible parameter
      variations between these areas, in the different matrices and seasons in the
      Southern region of Brazil. Six areas were selected (urban and forest), assigned
      to the rural/urban and urban/industrial matrices belonging to the watershed of
      the Rio dos Sinos, Brazil. The following parameters were analyzed: Index of
      photobiont vitality (IPV), photosynthetic pigments (chlorophyll, carotene, and
      pheophytin) and metals (Cu, Cr, Zn, Pb, and Ni) in the thallus of the lichen. The
      data were analyzed by an ANOVA one way, Pearson correlation test, and principal
      component analysis (PCA). Variations in the morphophysiological parameters were
      recorded in all the areas revealing significant differences. The lowest IPV
      values and highest concentration of metals were recorded in the urban
      environment, while low chlorophyll levels were found in the forest areas. The PCA
      showed a distinction between the areas and the season. The level of urbanization,
      vehicle traffic, and the weather conditions might have influenced the results.
      The use of P. tinctorum, the index of photobiont vitality and chlorophyll and
      pheophytin content, has proved to be an efficient tool to diagnose the air
      quality in the areas analyzed, allowing its use as a model in air monitoring
      studies, both in urban and forest areas, as well as in distinct matrices in the
      subtropical region.

PMID- 30276688
TI  - Hybrid UV-C/microfiltration process in membrane photoreactor for wastewater
      disinfection.
AB  - A novel hybrid UV-C/microfiltration process for water disinfection is presented,
      and its application in continuous mode operation to the removal of different
      pathogen germs (Escherichia coli, Enterococcus faecalis, and Candida albicans)
      present in urban wastewater. The membrane photoreactor is based on porous
      stainless steel membranes coated with a TiO2 layer and illuminated by a UV-C lamp
      (254 nm). A valve actuator in the outlet of the UV-C stream allows operation of
      the system under conditions of constant transmembrane pressure (TMP) keeping the
      UV-C contact time in few seconds, significantly lower than the typical
      irradiation time employed in TiO2 photocatalytic processes. An E. coli removal of
      up to 4-log in the permeate stream and up to 2-log in the UV-C outlet was
      achieved with a 0.2 MUm membrane operating with a TMP of 0.5 bar and a UV-C
      contact time as low as 8 s. The microbial balance data from the cells recovered
      from the membrane confirmed that 96-98% of the removed microorganisms died due to
      the UV-C action over the membrane surface. Modification of the membrane with a
      TiO2 layer has been also shown to be a suitable way to improve both the UV-C
      inactivation and the filtration efficiency. The results reported in this work
      constitute a proof of concept of the synergy between UV-C and filtration that can
      be achieved in a hybrid UV-C/microfiltration system, being a good example of
      process intensification where two products of different quality can be
      simultaneously obtained.

PMID- 30276690
TI  - Carbon dioxide emissions, total factor productivity, ICT, trade, financial
      development, and energy consumption: testing environmental Kuznets curve
      hypothesis for Tunisia.
AB  - The main objective of this study is to examine the linkage between CO2 emissions,
      total factor productivity as a measure of income, information and communication
      technology (ICT), trade, financial development, and energy consumption in Tunisia
      from 1975 to 2014. To achieve this goal, the autoregressive distributed lag
      (ARDL) with the break point method is performed. The results demonstrate the
      rejection of the Kuznets environmental curve (EKC) hypothesis by obtaining a
      higher value of the long-term total factor productivity parameter compared to the
      short-term one. Moreover, our result shows an insignificant impact of ICT on CO2
      emissions as a measure of pollution. In addition, trade, financial development,
      and energy consumption affect negatively the environmental quality. As a result,
      Tunisian policymakers should enhance the total factor productivity, expand the
      information and communication technology, further develop the financial sector,
      enhance the share of renewable energy consumption, and reduce the energy
      consumption resulting in import and export goods. These goals will be achieved by
      improving Tunisia's technological and innovation capacity, enhancing the use of
      ICT in transport, building, and industry sectors considered as the most pollutant
      ones, and creating renewable energy projects.

PMID- 30276691
TI  - Interactions between oil prices and financial sectors' performances: empirical
      evidence from Amman Stock Exchange.
AB  - The present study searches the effects of international oil prices on the
      performance of financial sector firms in the Amman Stock Exchange (ASE). Using
      the daily data which range from July 3, 2006 to April 12, 2018, we found that
      financial performance of the ASE firms is downturn during this data period and
      oil prices do not impact on these performances. It is found that downward
      movement of financial performances in the ASE is totally independent of the
      movements in international oil prices.

PMID- 30276689
TI  - Effect of Fe-functionalized biochar on toxicity of a technosol contaminated by Pb
      and As: sorption and phytotoxicity tests.
AB  - Biochar, produced by the pyrolysis of biomass under low oxygen conditions, has
      gathered attention in the last few years due to its capability to reduce
      metal(loid)s bioavailability and mobility in soils, as well as its beneficial
      effects on soil fertility. Indeed, biochar amendment to polluted soil induced
      usually an increase of pH, water holding capacity, and nutrient contents,
      associated with a decrease of metal(loid)s concentrations in soil pore water,
      through sorption. However, biochar has been shown efficient in sorbing cation
      pollutants, like Pb, but present a low sorption capacity towards anions like As.
      This contrasted behavior poses a problem, as most polluted soils are multi
      contaminated, with both cation and anion pollutants. One of the solutions to
      overcome such problem is to functionalize biochar, by modifying its surface.
      However, most studies actually focused on functionalization effect on
      metal(loid)s sorption towards batch experiments, and only a few dealt with
      modified biochar incorporation to the soil. Therefore, this study aimed (i) to
      assess the sorption capacity of hardwood biochars, harboring different particle
      sizes, towards Pb and As; (ii) to evaluate the effect of a Fe-functionalization
      on Pb and As sorption; and (iii) to validate the results, in a phytotoxicity test
      using Phaseolus vulgaris as bioindicator plant. The batch experiments showed that
      all four biochars were able to efficiently sorb Pb, the fine biochars showing
      higher sorption values than the coarse biochars. As sorption was very low. Fe
      coating increased As sorption value, while having no effect on Pb sorption.
      However, when incorporated in the soil, Fe-coated biochar did not improve soil
      physico-chemical properties compared to the pristine biochar; especially, it did
      not reduce As soil pore water concentrations. Finally, bean plant did not show
      differences in terms of biomass production between the two biochars incorporated
      into polluted soil, demonstrating that Fe-functionalization did not improve
      biochar capacity to decrease soil toxicity.

PMID- 30276692
TI  - Evolution of inorganic pollutants from landfills in shallow aquifers of different
      hydrogeological systems in Lithuania.
AB  - This study examines the patterns of evolution in inorganic macrocomponent
      speciation and the saturation state of the landfill leachate-polluted groundwater
      of three closed unlined landfills that are located in different hydrogeological
      systems (open, semi-open and closed) but are similar in both their volumes of
      landfill waste and the hazard levels of their landfill pollutants. Multivariate
      statistical analysis and geochemical modelling were conducted. The results showed
      that as the intensity of landfill pollution dispersion in groundwater along the
      flow path decreased, hydrochemical and hydrodynamic processes occurred with
      different intensities in open, semi-open and closed hydrogeological systems. In
      the open hydrogeological system, the processes of sulphate reduction, iron
      oxidation and chloride dilution and dispersion were up to 10-30% more intensive
      than those in the semi-open and closed hydrogeological systems. In the semi-open
      and closed hydrogeological systems, the processes of calcium, magnesium and iron
      carbonate equilibrium shifting towards carbonate precipitation were up to 15-40%
      more intensive than those in the open hydrogeological system. The results
      obtained in this research may be used to predict the dispersion of pollution in
      the groundwater of landfills located in similar hydrogeological systems and to
      facilitate the selection of prevention measures to limit pollution dispersion in
      groundwater.

PMID- 30276693
TI  - A comparative evaluation of the performance of full-scale high-rate methane
      biofilter (HMBF) systems and flow-through laboratory columns.
AB  - Methane biofilter (MBF) technology, a cost effective method to control
      atmospheric emission of CH4, is usually developed as a passively aerated system
      to control low-volume point-source emissions such as those from landfills with
      gas collection systems. Actively aerated high-rate methane biofilter (HMBF)
      systems are designed to overcome the shortcomings of passively aerated systems by
      ensuring the entire filter bed is utilized for CH4 oxidation. Flow-through column
      experiments point to the fact that CH4 oxidation rates of actively aerated
      systems could be several times higher than that of passively aerated systems.
      However, reports of the performance of field HMBF systems are not available in
      literature. Furthermore, there are no studies that demonstrate the possibility of
      using laboratory data in the design and operation of field systems. The current
      study was conducted to fill this research gap and involve a comparative study of
      the performance of laboratory columns to field performance of a HMBF system using
      solution gas produced at an oil battery site as the CH4 source. The actively
      aerated column studies confirmed past results with high CH4 oxidation rates; one
      column received air at two injection points and achieved an oxidation rate of
      1417 g/m3/d, which is the highest reported value to date for compost-filled
      columns. Subsequent studies at a specially designed field HMBF filled with
      compost showed a higher oxidation rate of 1919 g/m3/d, indicating the possibility
      of exceeding the high CH4 oxidation rates observed in the laboratory. The
      achievement of observed field oxidation rates being higher than those in the
      laboratory is attributed to the capability of maintaining higher temperatures in
      field HMBFs. Furthermore, results show that field HMBFs could operate at lower
      than stoichiometric air to CH4 ratios, and lower retention times than that of
      laboratory columns. Results indicated that laboratory columns may not truly
      represent field behavior, and said results could only be used in the preliminary
      design of field HMBFs.

PMID- 30276694
TI  - Submicron particle number doses in the human respiratory tract: implications for
      urban traffic and background environments.
AB  - The deposition of ambient submicron particles in the different parts of the human
      respiratory tract (HRT) was, for the first time, estimated for males and females
      from different age classes (children-adults-seniors) of urban population in the
      city of Thessaloniki, northern Greece, during the cold and the warm period of the
      year. Outdoor daily and hourly particle number doses in the different regions of
      the HRT, i.e., the extra-thoracic (ET), tracheobronchial (TB), and the acinar
      (AC) regions, were calculated by employing the Multiple-Path Particle Dosimetry
      (MPPD) model. Because of the absence of information being available for the
      hygroscopic properties of particles, three different particle hygroscopicity
      scenarios were considered: (i) non-hygroscopic (i.e., raw model estimations),
      (ii) nearly hydrophobic, and (iii) hygroscopic particles. When hygroscopic
      properties were considered, we found a remarkable reduction (up to ~ 55%) in the
      estimated total particle number doses in comparison to the non-hygroscopic
      particle scenario. Furthermore, we found that the size distribution pattern of
      the particle doses within the different parts of the HRT was strongly affected by
      particles' hygroscopic properties with the non-hygroscopic particle scenario
      significantly overestimating the particle doses in the sub-100-nm range, while
      underestimating the doses of larger particles. On the contrary, the deposition
      density appeared to be negligibly affected by the particles' hygroscopic
      properties, implying the existence of a possible threshold in the number of
      particles deposited per airway surface area. Similarly, the lobar particle number
      deposition fraction was unaffected by the hygroscopic properties of particles, as
      well as the ambient particle size distribution and the individuals' physiological
      parameters. The total particle number deposition doses estimated here are within
      the range of the corresponding values reported for other urban environments. It
      is hoped that our findings could contribute to better understanding of submicron
      particle exposure and add to the development of more sufficient methods to
      evaluate the related health impacts.

PMID- 30276695
TI  - The effects of ash inside a platinum-based catalyst diesel particulate filter on
      particle emissions, gaseous emissions, and unregulated emissions.
AB  - Ash deposited in the DPF cannot be burnt, which will affect the service life of
      DPF. However, previous works focused on the effect of ash on the engine exhaust
      emissions are limited. Therefore, the influence of ash on the emissions was
      studied in this work. The particle emissions, the gaseous emissions, and the
      unregulated emissions (carbonyl compounds and volatile organic compounds) were
      measured by an AMA4000 gaseous analyzer, ELPI, HPLC, and GC-MS, respectively.
      Research results indicate that the filtration efficiency decreases by 0.57-4.49%
      for accumulation mode particle of particulate matter, while it has very little
      effects on the other type and the particle number in the presence of ash. For
      regular gaseous pollutions, ash has no influence on CO2 and NOx emission, while
      CO and THC increase by 68.2% and 91.0%, respectively. For unregulated emissions,
      overall, carbonyl compounds increase by 41-150% and the BTEX decreases by 8.6
      23.6% after ash formed. The change is mainly caused by the increase in the
      exhaust backpressure that plays a key role.

PMID- 30276696
TI  - VegeSafe: a community science program generating a national residential garden
      soil metal(loid) database.
AB  - VegeSafe is a national community science initiative aimed at characterising soils
      in Australian residential gardens and community gardens. The program has been
      operating for over 5 years and has generated soil metal(loid) data from over 8600
      residential garden and community garden soil samples, submitted by almost 2000
      community scientists. The VegeSafe program represents the largest archive of soil
      metal(loid) data and associated metadata for residential garden soils in
      Australia. Samples were collected across Australia, with 61% of samples collected
      from NSW (n = 5284), Victoria (VIC) 20% (n = 1688) of samples and Queensland
      (QLD) 7% (n = 592) of samples. Soil metal(loid) data obtained by analysis of bulk
      soil samples by portable X-ray florescence spectrometry (pXRF) for As, Cu, Cr Mn,
      Pb and Zn showed spatial patterns of greater soil metal(loid) concentrations
      around city areas, particularly in NSW and VIC. The Australian Health
      Investigation Levels for low-density residential land uses (HIL-A) were used in
      this study as guideline values for soil metal(loid) concentrations. Overall,
      there was a relatively small number of HIL-A exceedances in the dataset, with
      most metal(loid)s exceeding their HIL-A concentration in < 5% of incidences. The
      notable exception to this was for Pb, which had HIL-A (300 mg/kg) exceeded in 27%
      (n = 1427) of samples in NSW, 17% (n = 280) in VIC and 10% (n = 61) in QLD.
      Through the power of community engagement and community science, the VegeSafe
      program presents an unprecedented insight into soil metal(loid) concentrations in
      Australian residential gardens.

PMID- 30276697
TI  - Phosphorus removal from wastewater using eggshell ash.
AB  - Eggshell ash was used as an adsorbent to remove phosphorus from wastewater.
      Adsorbent dose, initial phosphorus concentration, and contact time were
      investigated to determine the optimum conditions. Results indicate that 5 g of
      eggshell ash adsorbent with 1.5 mg L-1 of initial phosphorus concentration
      removed over 90% of the phosphorus. When the temperature was increased,
      phosphorus removal potential also increased. Specific surface area, morphological
      features, and structure of the adsorbent were characterized by Brunauer-Emmett
      Teller (BET) surface area analysis, scanning electron microscopy with energy
      dispersive X-ray spectrometer (SEM-EDS), and X-ray diffraction (XRD). Results
      showed prominent calcium, magnesium, and phosphorus in the eggshell ash surface
      after adsorption. The elemental composition of eggshell ash surfaces before
      adsorption did not contain phosphorus, revealing that calcium carbonate-based
      eggshell ash was co-precipitated with calcium phosphate. The adsorption mechanism
      was studied by applying Langmuir and Freundlich isotherm models. Experimental
      data fit well with the Langmuir model, which indicates monolayer adsorption.
      Eggshell ash was also applied as an adsorbent in wastewater at Srinakharinwirot
      University dormitories, resulting in 80% phosphorus removal within 2 h. These
      findings indicated that eggshell ash could be applied as an adsorbent for
      phosphorus treatment and removal from domestic and industrial wastewater.

PMID- 30276698
TI  - Priming with ACC-utilizing bacterium attenuated copper toxicity, improved
      oxidative stress tolerance, and increased phytoextraction capacity in wheat.
AB  - The major challenges for the plants growing in metal-contaminated soils are
      deficiency of nutrients, biomass reduction, and severe oxidative damages in the
      presence of heavy metals. In this regard, our aim was to overcome these
      challenges through the use of efficient microbial strains in metal-polluted soils
      and to assess its/their physiological and biochemical effects. In the current
      study, a copper (Cu)-resistant bacterium was isolated from the rhizospheric soil
      of 'Ziziphus nummularia' and evaluated for its ability to promote the wheat
      growth under the gradient stress of copper. Based on 16S rRNA gene sequencing,
      the isolate was identified as Pantoea sp. Among the plant growth promoting tests,
      the isolate showed the production of indole acetic acid, solubilization of
      inorganic phosphate, and ACC deaminase activity. Also, the isolate showed
      resistance to many heavy metals and antibiotics and increased the water-soluble
      copper in solution. The results of pot studies showed that bacterial application
      promoted various growth parameters of wheat plants and also enhanced the Cu
      uptake of wheat from the Cu-amended soil. The results showed that enhancement of
      Cu stress (100 to 300 mg kg-1) resulted in a decrease in various compatible
      solutes such as proline, total soluble sugars, and total protein content, and
      increase in the level of malondialdehyde (MDA), latter of which is the indicator
      of oxidative stress. Bacterial treatment markedly increased the proline, soluble
      sugar, total protein content, and decreased the MDA content under Cu stress. In
      addition, bacterial inoculation significantly alleviated the harmful effect of
      metal toxicity by decreasing the activation of ROS molecules including superoxide
      (O2-) and hydrogen peroxide (H2O2). The activation of various antioxidative
      enzymes such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)
      was noted following bacterial inoculation under Cu stress. Therefore, the present
      study demonstrates the potential of the isolate Pantoea sp. ZNP-5 to improve the
      growth and phytoextraction of metal from the metal-polluted soil through the
      polyphasic mechanism of action.

PMID- 30276699
TI  - Studies on the growth and mortality of Indian River shad, Gudusia chapra
      (Hamilton, 1822) from Panchet reservoir, India.
AB  - The Indian river shad, Gudusia chapra (Hamilton, 1822), is a commercially
      important freshwater clupeid that contribute to the livelihood of subsistence and
      marginal fisheries in inland open waters of India and its adjacent countries. The
      present study was carried out on the growth and mortality of Indian River shad,
      Gudusia chapra (Hamilton, 1822) based on the commercial length-frequency data
      collected monthly during October 2014 to September 2015 of a large reservoir
      located in the border of Jharkhand and West Bengal. The ELEFAN-I (Electronic
      Length Frequency Analysis) module in FiSAT (FAO-ICLARM Stock Assessment Tools)
      was used for estimation of growth parameters (Linfinity, K). The total mortality
      was estimated following Pauly (ICLARM Fishbyte 2(1):9-13, Pauly 1983) whereas
      exploitation ratio and maximum sustainable yield were calculated following
      Gulland (1979). The asymptotic length (Linfinity) and growth coefficient (K) were
      estimated as 194 mm and 1.23 year-1, respectively. The species grows to 141.56
      and 182.91 mm at the end of the 1st and 2nd years of life. The total natural and
      fishing mortalities were 6.63, 2.45 and 4.18 year-1 respectively. The value of
      growth performance index was 2.69. The exploitation ratio (E) was estimated as
      0.63. As the exploitation ratio (E) is slightly beyond the optimum, there is
      likelihood of some threat of overexploitation. Though recruitment was continuous,
      major pulse was observed during April-May. The present investigation is a first
      report from Indian reservoir. The maximum sustainable yield of this species was
      estimated as 485.6 t against the present annual yield of 612.3 t. Avoiding
      overfishing and wise use of available resources are of prime importance for
      sustainable fishery management of the reservoir.

PMID- 30276700
TI  - Dynamics of phosphorus content and the activity of phosphatase in forest soil in
      the sustained nitrogen compounds emissions zone.
AB  - This paper summarizes research work on the seasonal and profile dynamics of
      phosphorus content and the activity of phosphatase in soil next to the nitrogen
      industry. The results are presented of the total phosphorus (TP) and available
      phosphorus (AP) content and the alkaline phosphatase (AlP) and acid phosphatase
      (AcP) against the basic physicochemical properties (clay, pH, total organic
      carbon, total nitrogen). Three soil profiles were sampled from Brunic Arenosols
      0.8, 2.0, and 2.5 km away from the nitrogen plant. The control profile was taken
      from the Tuchola Forest. The soil was collected in both spring and autumn. The
      results showed that the total phosphorus content was higher in spring than in
      autumn (the value of index of changes in time TI < 0) contrary to available
      phosphorus (TI > 0) and in both seasons in surface soils, the lowest, in profile
      I. Both total and available phosphorus decreased with depth along the soil
      profiles. The distribution index (DI) calculated for total phosphorus in surface
      soils demonstrated a rather moderate accumulation, while DI value for available
      phosphorus for profile III, a considerable accumulation. The availability factor
      (AF) for all the soil samples was above the threshold of phosphorus load (2%) in
      the two seasons in this study (from 2.00 to 10.13% for spring and from 3.92 to
      21.19% for autumn), suggesting that the transformation rate from TP to AP was
      high, and AP supply for plant growth was sufficient. The correlation analysis
      showed a significant and positive correlation of available phosphorus with soil
      properties such as total organic carbon (r = 0.577), total nitrogen (r = 0.512),
      and clay (r = 0.493); however, there was no correlation with the activity of
      phosphatases.

PMID- 30276701
TI  - Characteristics and source apportionment of winter black carbon aerosols in two
      Chinese megacities of Xi'an and Hong Kong.
AB  - Black carbon (BC) aerosols were observed over Xi'an (XA) and Hong Kong (HK) to
      better compare its properties and sources in two geographically separate regions
      in China. High-BC (7.9 +/- 3.3 MUg.m-3) and -PM2.5 (182 +/- 80.5 MUg.m-3)
      concentrations were observed in XA, and these were much higher than those in HK
      (BC, 3.2 +/- 0.9 MUg.m-3; PM2.5, 34.5 +/- 9.3 MUg.m-3). The contribution of BC to
      PM2.5 in HK reached 10.7%, which was ~ 1.5 times than that in XA (7.6%). The
      results emphasized that BC played an important role in HK PM2.5. The diurnal
      distribution of HK BC was highly correlated with vehicle emissions during the
      daytime; it peaked during heavy traffic times. Whereas XA BC exhibited flat
      distribution owing to stable BC sources. It is not markedly driven by traffic
      patterns. Additionally, the potential source contribution function (PSCF)
      analysis showed that XA BC mainly originated from local emissions while nearly
      half of the HK BC originated from distant sources, such as industrial emissions
      from northeastern regions and ship emissions from marine regions. These
      anthropogenic BC sources were found to be regional in nature based on multilinear
      engine (ME-2) analysis. Specifically, the XA BC sources were dominated by three
      factors: 22.5% from coal burning, 19.6% from biomass burning, and 32.9% from
      vehicle emissions. In HK, the majority of BC contributions originated from
      vehicle and ship emissions (78.9%), while only 14.5% and 1.5% originated from
      coal and biomass burning from residential combustion, as well as industrial and
      power plants in inland China.

PMID- 30276702
TI  - Sulfate supply enhances cadmium tolerance in Vicia faba L. plants.
AB  - Sulfur deficiency and cadmium (Cd) pollution are two ubiquitous constraints
      affecting plant growth in agricultural soils. However, facing the situation of
      sulfur deficiency, whether surplus sulfate supply can affect Cd toxicity in
      plants is still unclear. Therefore, in the present study, experiments with
      deficient, sufficient, and excess sulfate levels under Cd stress were conducted
      in faba bean plants hydroponically. We found that sulfate supply significantly
      increased biomass of Cd-stressed plants when compared with deficient sulfate
      treatment. Intriguingly, sulfate application also increased Cd concentrations in
      leaves. Based on increased Cd concentrations without retarding plant growth, we
      conclude that sulfate supply enhances Cd tolerance in faba bean plants. Sulfate
      application increased CdSO40 proportion in the growth medium which is partially
      related to the increase of Cd in plants because the diffusion of CdSO40 is faster
      than Cd2+ in plants. Further study on Cd localization showed that this heavy
      metal was prone to accumulate in the epidermis of leaves as affected by sulfate
      which might contribute to enhancement of Cd tolerance. Oxidative stress induced
      by Cd toxicity was alleviated by surplus sulfate supply compared with deficient
      sulfate. Although capacities of total antioxidants were increased by sulfate in
      Cd-stressed plants, phenolic compounds as one kind of important antioxidants were
      unchanged, suggesting that sulfate has no effect on phenolic compounds for
      scavenging ROS under Cd stress. Taken together, sulfate accelerates Cd
      accumulation in the epidermis of leaves in faba bean giving rise to higher Cd
      tolerance.

PMID- 30276703
TI  - Validity of Social Support Scales Utilized Among HIV-Infected and HIV-Affected
      Populations: A Systematic Review.
AB  - Social support enhances self-management and prevention of behaviors and is
      typically assessed using self-report scales; however, little is known about the
      validity of these scales in HIV-infected or affected populations. This systematic
      review aims to identify available validated social support scales used in HIV
      infected and HIV-affected populations. A systematic literature search using key
      search terms was conducted in electronic databases. After rounds abstract
      screenings, full-text reviews, and data abstraction 17 studies remained, two of
      which assessed multiple social support scales, which increased number of scales
      to 19. Most scales assessed positive social support behaviors (n = 18). Most
      scales assessed perceived social support (n = 14) compared to received social
      support. Reliability ranged from 0.67 to 0.97. The most common forms of
      validation reported were content validity and construct validity and the least
      was criterion-related validity. Future research should seek to build evidence for
      validation for existing scales used in HIV-infected or HIV-affected populations.

PMID- 30276704
TI  - Special announcement-procedural sedation: a position paper of the Canadian
      Anesthesiologists' Society.

PMID- 30276705
TI  - In reply: Clarification on: "Pectoral nerves I block is associated with a
      significant motor blockade with no dermatomal sensory changes".

PMID- 30276706
TI  - Accuracy of diagnostic tests and a new algorithm for diagnosing cytomegalovirus
      colitis in inflammatory bowel diseases: a diagnostic study.
AB  - PURPOSE: The optimal method for detecting CMV colitis in patients with
      inflammatory bowel disease (IBD) has not been established. We wanted to
      investigate which diagnostic test would be most accurate when defining CMV
      colitis rather by the further clinical course than by using another diagnostic
      modality. METHODS: All consecutive patients with moderately or severely active
      IBD who had been tested for CMV by PCR, histology, or antigenemia assay at the
      two campuses CBF and CCM of the Charite - Universitatsmedizin Berlin between
      September 2006 and September 2009 were included in this retrospective study.
      During that time, in patients with a positive CMV test, immunosuppressive
      treatment of any kind was immediately reduced and antiviral treatment was
      started. This allowed identifying patients who responded to antiviral treatment
      and those who only responded to later escalation of immunosuppressive therapy.
      RESULTS: One hundred and nine patients were identified, out of whom nine were
      considered to have clinically relevant CMV colitis. Sensitivity and specificity
      were 1 and 0.94 for CMV PCR and 0.5 and 1 for pp65 antigen immunofluorescence
      assay from peripheral blood, 0.67 and 0.98 for immunohistochemistry, and 0.17 and
      0.98 for hematoxylin-eosin staining. When using absence of leukocytosis,
      splenomegaly, and steroid refractory disease as clinical parameters to test for
      CMV colitis, blood CMV PCR and immunohistochemistry were able to exclude CMV
      colitis in negative patients with a 75% likelihood of positive patients to have
      clinically relevant CMV colitis. CONCLUSIONS: Blood-based CMV PCR together with
      simple clinical parameters can exclude clinically relevant CMV colitis at a high
      specificity.

PMID- 30276707
TI  - Viral diseases meet omics: Time for systems virology.

PMID- 30276708
TI  - Genetically modified immune cells for cancer immunotherapy.

PMID- 30276709
TI  - Profile of Dr. Hualiang Jiang.

PMID- 30276711
TI  - Marine chitinolytic enzymes, a biotechnological treasure hidden in the ocean?
AB  - Chitinolytic enzymes are capable to catalyze the chitin hydrolysis. Due to their
      biomedical and biotechnological applications, nowadays chitinolytic enzymes have
      attracted worldwide attention. Chitinolytic enzymes have provided numerous useful
      materials in many different industries, such as food, pharmaceutical, cosmetic,
      or biomedical industry. Marine enzymes are commonly employed in industry because
      they display better operational properties than animal, plant, or bacterial
      homologs. In this mini-review, we want to describe marine chitinolytic enzymes as
      versatile enzymes in different biotechnological fields. In this regard,
      interesting comments about their biological role, reaction mechanism, production,
      functional characterization, immobilization, and biotechnological application are
      shown in this work.

PMID- 30276710
TI  - The role of drug-induced sleep endoscopy: predicting and guiding upper airway
      surgery for adult OSA patients.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is a common sleep disorder that can be
      corrected with upper airway surgery. Prior to surgery, drug-induced sleep
      endoscopy (DISE) is routinely used to evaluate obstruction sites and severity.
      Evidence suggests that the findings of DISE may relate to the final surgical
      outcome. Therefore, we evaluated the ability of drug-induced sleep endoscopy to
      predict the final effect of upper airway surgery and potentially to guide
      surgical treatment decision-making. METHODS: A retrospective analysis was
      conducted on 85 adult patients with OSA (50 men with mean apnea-hypopnea index
      [AHI] 30 +/- 15 events/h) who underwent DISE followed by tonsillectomy,
      uvulopalatopharyngoplasty (UPPP), or a combination of the two. Surgery outcome
      was evaluated at follow-up by polysomnography. Success response to surgery was
      defined as a postoperative value of the AHI< 20 events/h and more than 50%
      postoperative reduction of AHI. RESULTS: Of the 85 patients evaluated, 48 (53%)
      were responders. DISE revealed significant differences between the two groups.
      Specifically, complete circumferential collapse at the velum and complete
      anterior-posterior collapse at the tongue base occurred at higher frequencies in
      nonresponders. In contrast, the presence of grade 3-4 tonsillar hypertrophy and
      anterior-posterior mild/partial collapse at the velum were positively associated
      with responders. CONCLUSIONS: Our results suggest that DISE may help predict the
      final outcome of tonsillectomy, UPPP, or a combination of the two in adult
      patients with OSA. The use of DISE shows potential to guide treatment decisions
      for individual patients with OSA.

PMID- 30276713
TI  - The accD3 gene for mycolic acid biosynthesis as a target for improving fatty acid
      production by fatty acid-producing Corynebacterium glutamicum strains.
AB  - We have recently developed Corynebacterium glutamicum strains that produce free
      fatty acids in culture supernatant due to enhanced fatty acid biosynthesis. Of
      these producing strains, the basic producer PAS-15 has a defect in the gene for a
      fatty acid biosynthesis repressor protein, and the advanced producer PCC-6 has
      two additional mutations to augment the production by strain PAS-15. The aim of
      the present study was to obtain novel genetic traits for improving fatty acid
      production by these producers. A new mutant with increased production derived
      from strain PAS-15 had a missense mutation in the accD3 gene (mutation
      accD3A433T), which is involved in the biosynthesis of mycolic acids that are cell
      envelope lipids of C. glutamicum, as the causal mutation. Mutation accD3A433T was
      verified to reduce the AccD3 enzymatic activity and increase fatty acid
      production in strain PAS-15 by 1.8-fold. Deletion of the accD3 gene in strain PAS
      15, which was motivated by the characteristic of mutation accD3A433T, increased
      fatty acid production by 3.2-fold. Susceptibility of strain PAS-15 to vancomycin
      was significantly increased by accD3 gene deletion and by mutation accD3A433T to
      the intermediate level, suggesting that the cell envelope permeability barrier by
      mycolic acids is weakened by this engineering. Furthermore, mutation accD3A433T
      also increased fatty acid production in strain PCC-6 by 1.3-fold. These increased
      production levels were suggested to be involved not only in the redirection of
      carbon flux from mycolic acid biosynthesis to fatty acid production but also in
      the permeability of the cell envelope.

PMID- 30276712
TI  - Global and pathway-specific transcriptional regulations of pactamycin
      biosynthesis in Streptomyces pactum.
AB  - Pactamycin, a structurally unique aminocyclitol natural product isolated from
      Streptomyces pactum, has potent antibacterial, antitumor, and anti-protozoa
      activities. However, its production yields under currently used culture
      conditions are generally low. To understand how pactamycin biosynthesis is
      regulated and explore the possibility of improving pactamycin production in S.
      pactum, we investigated the transcription regulations of pactamycin biosynthesis.
      In vivo inactivation of two putative pathway-specific regulatory genes, ptmE and
      ptmF, resulted in mutant strains that are not able to produce pactamycin. Genetic
      complementation using a cassette containing ptmE and ptmF integrated into the S.
      pactum chromosome rescued the production of pactamycin. Transcriptional analysis
      of the DeltaptmE and DeltaptmF strains suggests that both genes control the
      expression of the whole pactamycin biosynthetic gene cluster. However, attempts
      to overexpress these regulatory genes by introducing a second copy of the genes
      in S. pactum did not improve the production yield of pactamycin. We discovered
      that pactamycin biosynthesis is sensitive to phosphate regulation. Concentration
      of inorganic phosphate higher than 2 mM abolished both the transcription of the
      biosynthetic genes and the production of the antibiotic. Draft genome sequencing
      of S. pactum and bioinformatics studies revealed the existence of global
      regulatory genes, e.g., genes that encode a two-component PhoR-PhoP system, which
      are commonly involved in secondary metabolism. Inactivation of phoP did not show
      any significant effect to pactamycin production. However, in the phoP::aac(3)IV
      mutant, pactamycin biosynthesis is not affected by external inorganic phosphate
      concentration.

PMID- 30276714
TI  - Transcriptome analysis of the response of silkworm to drastic changes in ambient
      temperature.
AB  - Bombyx mori is a poikilothermic insect and is economically important for silk
      production. Drastic changes in the ambient temperature have a negative impact on
      sericulture. However, the reason as to why high temperature is associated with
      the occurrence of diseases in silkworm and the response of silkworm to low
      temperature remain unclear and were the focus of the present study. Dazao
      silkworm exposed to 13  degrees C (DZ-13), 25  degrees C (DZ-25), and 37  degrees
      C (DZ-37) were used for RNA-seq analysis. There were 478 and 194 upregulated
      differentially expressed genes (DEGs) in DZ-13 and DZ-37 while 49 and 273
      downregulated DEGs in DZ-13 and DZ-37, respectively. Eight DEGs were co
      upregulated, in which seven genes were for heat shock proteins (Hsps), implying
      that Hsps play important roles in the tolerance of silkworm to high and low
      temperature. Gene ontology analysis revealed that the developmental process was
      downregulated in DZ-13. All the DEGs in the oxidative phosphorylation and insulin
      signaling pathways were upregulated in DZ-13. Several cuticular proteins and ATP
      synthesis-related genes were upregulated in DZ-13, suggesting that thickening of
      the cuticle and increase in the ATPase expression would help silkworms to protect
      themselves from low temperature-induced stress. Several immune-related genes,
      such as BmRel and BmSerpin-2, were downregulated in DZ-37, revealing that the
      resistance of silkworm is decreased under high temperature shock resulting in
      susceptibility to pathogens. Thus, the increase in the thermo-tolerance of
      silkworm should be related to the enhancement in the pathogen resistance.

PMID- 30276715
TI  - The time response of anaerobic digestion microbiome during an organic loading
      rate shock.
AB  - Knowledge of connections between operational conditions, process stability, and
      microbial community dynamics is essential to enhance anaerobic digestion (AD)
      process efficiency and management. In this study, the detailed temporal effects
      of a sudden glycerol-based organic overloading on the AD microbial community and
      process imbalance were investigated in two replicate anaerobic digesters by a
      time-intensive sampling scheme. The microbial community time response to the
      overloading event was shorter than the shifts of reactor performance parameters.
      An increase in bacterial community dynamics and in the abundances of several
      microbial taxa, mainly within the Firmicutes, Tenericutes, and Chloroflexi phyla
      and Methanoculleus genera, could be detected prior to any shift on the reactor
      operational parameters. Reactor acidification already started within the first 24
      h of the shock and headed the AD process to total inhibition in 72 h alongside
      with the largest shifts on microbiome, mostly the increase of Anaerosinus sp. and
      hydrogenotrophic methanogenic Archaea. In sum, this work proved that AD microbial
      community reacts very quickly to an organic overloading and some shifts occur
      prior to alterations on the performance parameters. The latter is very
      interesting as it can be used to improve AD process management protocols.

PMID- 30276716
TI  - Proteomic characterization and antifungal activity of potato tuber proteins
      isolated from starch production waste under different temperature regimes.
AB  - Proteins were obtained from effluent of a starch manufacture by using different
      isolation temperatures (40, 60, 80, and 100  degrees C). The proteins, remaining
      in effluent after treatment of potato juice at 80 and 100  degrees C differed
      significantly in composition and in structural stability as well as in trypsin
      inhibitory and antifungal activities in comparison with the variants of 40 and 60
      degrees C. The protein samples of 80  degrees C exhibited the highest antifungal
      activity and its average value of IC50 against five strains of two Fusarium
      species was determined in average at 0.18 mg ml-1. The 80  degrees C protein
      samples consisted predominantly of low-molecular proteins (7-17 kDa) identified
      as potato tuber protease inhibitors I and II. Predominantly, protease inhibitors
      II were identified for the protein samples obtained by 100  degrees C and here we
      identified 7 spots in comparison with 12 identified for the 80  degrees C
      samples. Samples of 40 and 60  degrees C with low antifungal activities represent
      high variability of detected and identified proteins. We identified various
      representatives of aspartic, cysteine, and serine protease inhibitors in both
      types of samples. These samples also contained Kunitz-type protease inhibitors
      that were not found in the 80 and 100  degrees C samples which documented thermal
      unstableness of Kunitz-type protease inhibitors. Functional stability at high
      temperatures and antifungal activity of isolated potato protease inhibitors I and
      II support the potential of this fraction usage in food, feed, pharmaceutical, or
      agricultural industry and offer new products for starch manufactures. At the same
      time, utilization of the stable protein fraction of waste deproteinized potato
      water promotes exploitation of potato starch production resources.

PMID- 30276717
TI  - Mild Exercise Differently Affects Proteostasis and Oxidative Stress on Motor
      Areas During Neurodegeneration: A Comparative Study of Three Treadmill Running
      Protocols.
AB  - Proteostasis and oxidative stress were evaluated in motor cortex and spinal cord
      of aged Lewis rats exposed to 1 mg/kg/day of rotenone during 4 or 8 weeks, prior
      or after practicing three protocols of mild treadmill running. Results
      demonstrated that exercise done after the beginning of neurodegeneration reverted
      the increased oxidative stress (measured by H2O2 levels and SOD activity),
      increased neuron strength, and improved proteostasis in motor cortex. Spinal cord
      was not affected. Treadmill running practiced before neurodegeneration protected
      cortical motor neurons of the rotenone-exposed rats; but in this case, oxidative
      stress was not altered, whereas proteasome activity was increased and autophagy
      decreased. Spinal cord was not protected when exercise was practiced before
      neurodegeneration. Prolonged treadmill running (10 weeks) increased oxidative
      stress, autophagy, and proteasome activity, whereas neuron viability was
      decreased in motor cortex. In spinal cord, this protocol decreased oxidative
      stress and increased proteasome activity. Major conclusions were that treadmill
      running practiced before or after the beginning of neurodegeneration may protect
      motor cortex neurons, whereas prolonged mild running seems to be beneficial for
      spinal cord.

PMID- 30276718
TI  - Hydroxyurea Exposure and Development of the Cerebellar External Granular Layer:
      Effects on Granule Cell Precursors, Bergmann Glial and Microglial Cells.
AB  - The current paper presents a histological analysis of the cell death in the
      cerebellar external granular layer (EGL) following the treatment with a single
      dose (2 mg/g) of hydroxyurea (HU). The rats were examined at postnatal days (P)
      5, 10, and 15, and sacrificed at appropriate times ranging from 6 to 48 h after
      treatment administration. Studies were done in each cortical lobe (anterior,
      central, posterior, and inferior). The quantification of several parameters, such
      as density of 5-bromo-2'-deoxyuridine, TUNEL, vimentin, and tomato lectin-stained
      cells, revealed that HU compromises the viability of EGL cells. Our results
      indicate that P10 is a time of high vulnerability to injury. We also show here
      that the anterior and central lobes are the cortical regions most susceptible to
      the action of the HU. Additionally, our data also indicate that from 6 to 24 h
      after HU-exposure is a time-window of high sensibility to this agent. On the
      other hand, our ultrastructural analysis confirmed that HU administration
      produces the activation of apoptotic cellular events in the EGL, resulting in a
      substantial number of dying cells. Different stages of apoptosis can be observed
      in all cortical lobes at all investigated postnatal ages and survival times.
      Moreover, we observed that dying neuroblasts were covered by laminar processes of
      Bergmann glia, and that these unipolar astrocytes presented cytological features
      of phagocytes engulfing apoptotic bodies and cell debris. The electron microscopy
      study also revealed the participation of ameboid microglial cells in the
      phagocytosis of apoptotic cells in the regions of the EGL with extensive cell
      death.

PMID- 30276719
TI  - The Effect of Vancomycin on the Viability and Osteogenic Potential of Bone
      Derived Mesenchymal Stem Cells.
AB  - Traditionally, methicillin-resistant Staphylococcus aureus (MRSA) is treated with
      vancomycin, administrated intravenously or applied directly onto infected tissue.
      The effect of direct (as opposed to systemic) vancomycin treatment on bone
      formation and remodelling is largely unknown. The minimal inhibitory
      concentration (MIC) of vancomycin was determined by adding 200 MUL of different
      concentrations (1-20 MUg/mL) to actively growing cultures of S. aureus Xen 31
      (methicillin-resistant) and S. aureus Xen 36 (methicillin-sensitive),
      respectively, and recording changes in optical density over 24 h. Bone marrow
      derived and proximal femur-derived mesenchymal stem cells (bmMSCs and pfMSCs)
      from rat femora were exposed to 1 * MIC (5 MUg/mL) and 4 * MIC (20 MUg/mL) of
      vancomycin for 7 days. Cell viability was determined by staining with crystal
      violet and MTT (3-(4,5- di methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide),
      respectively, and osteogenic differentiation by staining with Alizarin Red S.
      Vancomycin had no effect on the viability of bmMSCs and pfMSCs, even at high
      levels (20 MUg/mL). The osteogenic differentiation of pfMSCs was partially
      inhibited, while osteogenesis in bmMSCs was not severely affected. The direct
      application of vancomycin to infected bone tissue, even at excessive levels, may
      preserve the viability of resident MSC populations.

PMID- 30276720
TI  - Survival and Goat Milk Acidifying Activity of Lactobacillus rhamnosus GG
      Encapsulated with Agave Fructans in a Buttermilk Protein Matrix.
AB  - Lactobacillus rhamnosus GG (L. rhamnosus GG) cells were encapsulated in
      buttermilk proteins by spray drying, alone (E), or with Agave tequilana fructans
      (CEF). Buttermilk proteins acted as a thermo-protector for the probiotic cells
      undergoing the spray-dried process. The addition of Agave fructans in CEF
      microcapsules significantly enhanced storage stability and survival to in vitro
      simulated gastrointestinal conditions, compared to E capsules. After 14 days
      storage at - 20  degrees C, the number of living cells in CEF microcapsules was
      in the order of 7.7 log CFU * mL-1 and the survivability in simulated
      gastrointestinal environment was 73.23%. Spray-dried microparticles were cultured
      in goat milk to study biomass production. Agave fructans offered a favorable
      microenvironment and better growth substrate. The population of CEF viable cells
      reached 1.08 +/- 0.02 * 1010 CFU * mL-1 after 18 h of fermentation. In contrast,
      the population of E viable cells were 3.0 +/- 0.01 * 109 CFU * mL-1. The
      generation time of CEF, L. rhamnosus GG was 15% faster than E, L. rhamnosus GG.
      Encapsulation with buttermilk proteins in the presence of Agave fructans by spray
      drying could be suitable for preservation of probiotic powders and may be for a
      more effective application of probiotics in goat dairy products.

PMID- 30276721
TI  - FGF8 induces therapy resistance in neoadjuvantly radiated rectal cancer.
AB  - PURPOSE: Therapy response to neoadjuvant radiochemotherapy (nRCT) of locally
      advanced rectal cancer varies widely so that markers predicting response are
      urgently needed. Fibroblast growth factor (FGF) and FGF receptor (FGFR) signaling
      is involved in pro-survival signaling and thereby may result in radiation
      resistance. METHODS: In a cohort of 43 rectal cancer patients, who received nRCT,
      we analyzed protein levels of FGF 8 and its downstream target Survivin by
      immunohistochemistry to assess their impact on nRCT response. In vitro resistance
      models were created by exposing colorectal cancer cell lines to fractionated
      irradiation and selecting long-term survivors. RESULTS: Our findings revealed
      significantly higher FGF8 and Survivin staining scores in pre-treatment biopsies
      as well as in surgical specimens of non-responsive compared to responsive
      patients. Functional studies demonstrated dose-dependent induction of FGF8 mRNA
      expression in mismatch-incompetent DLD1 cells already after one dose of
      irradiation. Surviving clones after one or two series of radiation were more
      resistant to an additional radiation fraction than non-irradiated controls and
      showed a significant increase in expression of the FGF8 receptor FGFR3 and of
      Survivin on both the RNA and the protein levels. CONCLUSION: The results of this
      study suggest that FGF8 and Survivin contribute to radiation resistance in rectal
      cancer and may serve as markers to select patients who may not benefit from
      neoadjuvant radiotherapy.

PMID- 30276722
TI  - Fixation of flail chest or multiple rib fractures: current evidence and how to
      proceed. A systematic review and meta-analysis.
AB  - PURPOSE: The aim of this systematic review and meta-analysis was to present
      current evidence on rib fixation and to compare effect estimates obtained from
      randomized controlled trials (RCTs) and observational studies. METHODS: MEDLINE,
      Embase, CENTRAL, and CINAHL were searched on June 16th 2017 for both RCTs and
      observational studies comparing rib fixation versus nonoperative treatment. The
      MINORS criteria were used to assess study quality. Where possible, data were
      pooled using random effects meta-analysis. The primary outcome measure was
      mortality. Secondary outcome measures were hospital length of stay (HLOS),
      intensive care unit length of stay (ILOS), duration of mechanical ventilation
      (DMV), pneumonia, and tracheostomy. RESULTS: Thirty-three studies were included
      resulting in 5874 patients with flail chest or multiple rib fractures: 1255
      received rib fixation and 4619 nonoperative treatment. Rib fixation for flail
      chest reduced mortality compared to nonoperative treatment with a risk ratio of
      0.41 (95% CI 0.27, 0.61, p < 0.001, I2 = 0%). Furthermore, rib fixation resulted
      in a shorter ILOS, DMV, lower pneumonia rate, and need for tracheostomy. Results
      from recent studies showed lower mortality and shorter DMV after rib fixation,
      but there were no significant differences for the other outcome measures. There
      was insufficient data to perform meta-analyses on rib fixation for multiple rib
      fractures. Pooled results from RCTs and observational studies were similar for
      all outcome measures, although results from RCTs showed a larger treatment effect
      for HLOS, ILOS, and DMV compared to observational studies. CONCLUSIONS: Rib
      fixation for flail chest improves short-term outcome, although the indication and
      patient subgroup who would benefit most remain unclear. There is insufficient
      data regarding treatment for multiple rib fractures. Observational studies show
      similar results compared with RCTs.

PMID- 30276723
TI  - Displaced distal radius fractures in children, cast alone vs additional K-wire
      fixation: a meta-analysis.
AB  - PURPOSE: Displaced distal radius fractures in children are common and often
      treated by reduction and cast immobilization. Redisplacement occurs frequently
      and may be prevented by additional treatment with K-wire fixation after initial
      reduction. This meta-analysis aims to summarize available literature on this
      topic and determine if primary K-wire fixation is the preferred treatment for
      displaced distal radius fractures in children. METHODS: A search in eight
      databases identified studies that compared cast immobilization alone to
      additional K-wire fixation as treatment for displaced paediatric distal radius
      fractures. The primary outcome was the redisplacement rate. Secondary outcomes
      were secondary reduction rate, range of motion and complications. This meta
      analysis was performed according to the preferred reporting items for systematic
      reviews and meta-analysis (PRISMA) statement. RESULTS: Three RCTs and 3 cohort
      studies, analysing 197 patients treated with cast immobilization alone and 185
      with additional K-wire fixation, were included in this meta-analysis.
      Redisplacement occurred less frequently after additional K-wire fixation than
      after cast alone (3.8 versus 45.7%; OR 0.07, 95% CI 0.03-0.15). Secondary
      reduction was performed in 59.8% of the redisplaced fractures. Complications,
      other than redisplacement, occurred more often after additional K-wire fixation
      than after cast alone (15.7 versus 3.6%). Range of motion did not differ after
      both treatments. CONCLUSIONS: Additional K-wire fixation is a suitable treatment
      to prevent redisplacement and secondary operations after initial reduction of
      displaced distal radius fractures in children, but is associated with post
      procedural complications. Additional K-wire fixation does not result in a better
      range of motion than cast immobilization alone. More research is needed to
      identify those patients who will benefit the most from K-wire fixation as a
      treatment for displaced distal radius fractures in children.

PMID- 30276724
TI  - Epidemiology and treatment of distal radius fractures: current concept based on
      fracture severity and not on age.
AB  - PURPOSE: A shift towards surgical treatment of distal radius fractures seems to
      be apparent. The purpose of the present study was to assess current
      epidemiological data, the fracture severity according to the AO classification
      and the changing trend in the treatment. METHODS: This study presents a
      retrospective review of 268 patients >= 18 years of age admitted to our level I
      trauma center with distal radius fractures between 2013 and 2015. The data were
      obtained from the hospital inpatient enquiry system and review of the
      radiological examinations. RESULTS: The ratio between males and females was
      87:181. The average age of the patients was 56.9 (18-99) years. A fall from
      standing position was the most common mechanism of injury. According to the AO
      classification, 43.3% were type A fractures, 13.1% type B, and 43.7% type C. As
      the intensity of the injury mechanism increased, the percentage of type C
      fractures also increased. A total of 61.9% of patients underwent surgery with
      open reduction and internal fixation with volar locking plates used as the
      preferred surgical treatment. Fracture severity correlated well with surgical
      decision. Elderly patients were just as likely to get surgical treatment as adult
      patients. CONCLUSIONS: Our findings confirmed the increasing popularity of
      surgical intervention with open reduction and internal fixation. Contrary to
      previous studies, the fracture type profile showed an equal proportion of type A
      and C fractures and the indication for surgical treatment correlated with
      fracture severity and not age.

PMID- 30276725
TI  - Circulation of Influenza Virus in the 2015/2016 Epidemic Season in Poland:
      Serological Evaluation of Anti-hemagglutinin Antibodies.
AB  - The diagnostic of influenza virus infections is possible using molecular biology
      methods as well as the analysis of anti-hemagglutinin (anti-HA) antibodies in the
      blood serum. The aim of this study was to determine the level of anti-HA
      antibodies in 7 age groups of patients during the 2015/2016 epidemic season in
      Poland. A total of 1050 serum samples were tested using the hemagglutination
      inhibition (HAI) assay. We confirmed the presence of anti-HA antibodies for the
      influenza virus strains: A/California/7/2009(H1N1)pdm09,
      A/Switzerland/9715293/2013(H3N2), and B/Phuket/3073/2013, which were the
      components of the influenza vaccine for the 2015/2016 epidemic season. The level
      of specific anti-HA antibodies was different in each age group. The geometric
      mean titers were highest at age 5-9 years, where the antibody protection level
      reached 61.3% against B/Phuket/3073/2013 and 52.7% for
      A/Switzerland/9715293/2013(H3N2) antigen. The antibody level amounted to 56.7%
      against for antigen B at age 45-64. In the remaining age groups, the protection
      levels for all hemagglutinin types did not exceed 50%. These findings confirm the
      urgent need to increase a persistently low influenza vaccination coverage in the
      Polish population, which may have had its part in the noticeable increase in the
      confirmed cases of influenza and influenza-like virus infection during the
      season.

PMID- 30276726
TI  - Influence of Socio-Economic Status on Lung Function in Male Adolescents in
      Tanzania.
AB  - A lower socio-economic status (SES) associates with increased morbidity and
      mortality. The goal of this study was to define the influence of SES on lung
      function in indigenous male adolescents (aged 12.8-24.5 years) in Tanzania. The
      subjects were subdivided into two age groups: <17.5 (n = 189) and >= 17.5 years
      of age (n = 101). They underwent anthropometric and spirometry evaluation. The
      SES was assessed on the basis of economic family resources and the subjects'
      nutritional status, and was stratified into three categories: SES-1 (low), SES-2
      (average), and SES-3 (high). Relative contributions of body mass index, chest
      expansion/mobility, waist-to-chest ratio, and SES to spirometry variables were
      statistically determined. We found significant differences in forced expiratory
      volume in 1 s (FEV1) and forced vital capacity (FVC) in the older, but not
      younger age group, by the SES category. The adolescents aged >=17.5 in high-SES-3
      category had FEV1 and FVC greater by 29.3% and 42.5%, respectively, than those in
      low-SES-1 category in the same age group. There also were differences between the
      two age groups. The mean FEV1 and FVC in adolescents of high-SES-3 category, aged
      >=17.5, were higher by 65.3% and 82.2%, respectively, than those in the
      corresponding SES-3 in adolescents aged <17.5. In younger adolescents, lung
      function variables associated mostly with body build parameters, whereas in older
      adolescents with SES. The study revealed a significant dependence of lung
      function, and thus plausibly a greater resistance to diseases, on the socio
      economic status. We conclude that the socio-economic status be taken into
      consideration in the assessment of lung function in epidemiological and public
      health programs, particularly in the context of the developing countries, to
      obtain the most reliable results.

PMID- 30276727
TI  - Rituximab in routine care of severe active rheumatoid arthritis : A prospective,
      non-interventional study in Germany.
AB  - OBJECTIVE: To assess safety, effectiveness and onset of effect of rituximab (RTX)
      in routine clinical treatment of severe, active rheumatoid arthritis (RA).
      METHODS: Prospective, multi-centre, non-interventional study in rheumatological
      outpatient clinics or private practices in Germany. RTX-naive adult patients were
      to receive RTX according to marketing authorisation and at their physician's
      discretion. Also according to their physician's discretion, patients could
      receive a second cycle of RTX (re-treatment = treatment continuation). Major
      outcome was the change in Disease Activity Score based on 28-joints count and
      erythrocyte sedimentation rate (DAS28-ESR) over 24 weeks and during 6 months of
      re-treatment. RESULTS: Overall, 1653 patients received at least one cycle RTX;
      99.2% of these had received disease-modifying antirheumatic drugs (DMARD) pre
      treatment and 75.5% anti-tumor necrosis factor(TNF)-alpha pre-treatment. After a
      mean interval of 8.0 months, 820 patients received RTX re-treatment. Mean DAS28
      ESR decreased from 5.3 at baseline to 3.8 after 24 weeks (-1.5 [95% confidence
      interval, CI: -1.6; -1.4]), and from 4.1 at start of cycle 2 to 3.5 at study end
      (change from baseline: -1.8 [95% CI: -2.0; -1.7]). Improvements in DAS28-ESR and
      Health Assessment Questionnaire (HAQ) score occurred mainly during the first 12
      weeks of RTX treatment, with further DAS28-ESR improvement until week 24 or month
      6 of re-treatment. Improvements in DAS28-ESR and EULAR responses were more
      pronounced in seropositive patients. RF was a predictor of DAS28-ESR change to
      study end. Safety analysis showed the established profile of RTX. CONCLUSION: RTX
      was safe and effective in a real-life setting with rapid and sustained
      improvement in RA signs and symptoms.

PMID- 30276728
TI  - Refractory chylous pleural effusion with systemic lupus erythematosus : Surgical
      treatment when steroid/immunosuppressant resistant.
AB  - We analyzed four cases of systemic lupus erythematosus (SLE) with chylous pleural
      effusion treated in our hospital from June 2013 to May 2017. The three females
      and one male ranged in age from 22 to 33 years. The length of disease course was
      20 to 120 months. Treatment with glucocorticoids and immunosuppressants
      (cyclophosphamide or cyclosporine A) did not reduce chylous pleural effusion.
      Lymphatic obstruction was found in all patients after direct lymphangiography and
      the pleural effusion was significantly reduced after surgery. A literature search
      identified six previously reported patients with SLE and chylous pleural
      effusion. Five were sensitive to classic immunosuppression treatment, probably
      due to early intervention. However, as shown here, the thoracic duct can be
      involved in SLE, leading to an intractable chylous pleural effusion with no
      response to medical treatment. Surgery would be a better choice when lymphatic
      mechanical obstruction is found.

PMID- 30276729
TI  - Making the Case for Functional Proteomics.
AB  - "Making the Case for Functional Proteomics" first differentiates the Functional
      Proteome from the products of genetic protein expression. Qualitatively, the
      prevalence of posttranslational modifications (PTMs) virtually insures that
      individual, functional proteins do not equate to their genetic expression
      counterparts. Quantitatively, considering the frequency of PTMs and a
      conservative estimate of the number of functional entities arising from protein
      interactions, the size of the Functional Proteome exceeds that of the human
      genome by at least two orders of magnitude. The human genome does not, cannot,
      map the Functional Proteome. Further, the collective genome of the human
      microbiome dwarfs the human genome. With these facts established, "Making the
      Case..." proceeds to examine Functional Proteomics (of which both "gene
      expression" and "epigenetics" are but parts of a larger whole) within the context
      of Systems Biology, concluding that functionally related networks comprise the
      dominant motif for biological activity. Creating just such a network focus is
      essential in not only expanding basic knowledge but also in applying that
      knowledge in the pragmatic efforts of drug and biomarker development. Outlines
      for development of drugs and biomarkers, as well as the realization of precision
      medicine, within a functional proteomics-based, network motif are provided. The
      chapter proceeds to asses both the knowledge base and the tools to fully embrace
      Functional Proteomics. Given the decades-long infatuation with the reductionism
      of genomics, it is not surprising that both the proteomics knowledge base and
      tools are assessed as poor to fair. However, even a minor shift in research
      funding and a renewed challenge to methods developers will rapidly improve the
      current situation. Adoption of the included "Roadmap" will realistically make the
      twenty-first century the century of a long-awaited revolution in biology.

PMID- 30276730
TI  - Methods to Monitor the Functional Subproteomes of SERPIN Protease Inhibitors.
AB  - Conformational variants of the unique family of protease inhibitors annotated as
      SERPINs are most often underrepresented in proteomic analyses. This limits
      understanding the complex regulation that this family of proteins presents to the
      networks within the protease web of interactions. Using bead-based separation
      provided by a family of proteomic enrichment products-notably AlbuVoidTM and
      AlbuSorbTM, we demonstrate their utility to satisfy investigations of serum
      SERPINs. We also suggest their use to develop functional profiles of the SERPIN
      proteoforms, and how those can establish relationships to disease phenotypes,
      gene mutations, and dysregulated mechanisms.

PMID- 30276731
TI  - Two-Dimensional 16-BAC/SDS Polyacrylamide Gel Electrophoresis of Mitochondrial
      Membrane Proteins.
AB  - The substitution of the reverse polarity benzyldimethyl-n-hexadecylammonium
      chloride (16-BAC) polyacrylamide gel electrophoresis (PAGE) for isoelectric
      focusing (IEF) in the first dimension of electrophoresis improves the solubility
      of extremely hydrophobic proteins and their recovery compared to conventional 2D
      IEF/SDS PAGE. The acidic environment of 16-BAC PAGE has also been shown to better
      preserve the labile methylation of basic proteins such as the histones. Several
      improvements of the 2D 16-BAC/SDS PAGE method are collectively described here
      with particular emphasis on the separation of mitochondrial membrane proteins of
      low molecular mass. Lowering the 16-BAC concentration 50-fold in the gel and
      buffers decreases the formation of mixed 16-BAC/SDS micelles, which otherwise
      interferes with the separation of very low molecular mass proteins in second
      dimension SDS PAGE, and consequently improved the resolution of mitochondrial
      membrane proteins in the 10-30 kDa range.

PMID- 30276732
TI  - Systematic Glycolytic Enzyme Activity Analysis from Human Serum with PEP
      Technology.
AB  - A functional proteomics technology was used to systematically monitor metabolic
      enzyme activities from resolved serum proteins produced by a modified 2-D gel
      separation and subsequent Protein Elution Plate, a method collectively called
      PEP. Both qualitative and quantitative differences in the metabolic enzyme
      activity could be detected between cancer patient and control group, providing
      excellent biomarker candidates for cancer diagnosis and drug development. This
      technology has a wide range of applications; it can be used for rapid functional
      protein purification and characterization as well as drug target identification
      and validation. The ability for the PEP technology to efficiently separate and
      recover functional proteins makes it useful for the analysis of any proteins and
      its variants; this is especially advantageous for enzyme families with large
      number of enzymes such as protein kinases, phosphatases, proteases, and metabolic
      enzymes.

PMID- 30276733
TI  - A Protein Decomplexation Strategy in Snake Venom Proteomics.
AB  - Snake venoms are complex mixtures of proteins and peptides that play vital roles
      in the survival of venomous snakes. As with their diverse pharmacological
      activities, snake venoms can be highly variable, hence the importance of
      understanding the compositional details of different snake venoms. However,
      profiling venom protein mixtures is challenging, in particular when dealing with
      the diversity of protein subtypes and their abundances. Here we described an
      optimized strategy combining a protein decomplexation method with in-solution
      trypsin digestion and mass spectrometry of snake venom proteins. The approach
      involves the integrated use of C18 reverse-phase high-performance liquid
      chromatography (RP-HPLC), sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE), and nano-electrospray ionization tandem mass
      spectrometry (nano-ESI-LC-MS/MS).

PMID- 30276734
TI  - Fractionation Techniques to Increase Plant Proteome Coverage: Combining
      Separation in Parallel at the Protein and the Peptide Level.
AB  - Peptide spectral libraries enable targeted identification and quantitation of low
      abundance proteins in a complex plant proteome. Here we describe parallel protein
      and peptide fractionation techniques to improve plant proteome coverage and
      facilitate construction of spectral libraries.

PMID- 30276735
TI  - A Systematic Analysis Workflow for High-Density Customized Protein Microarrays in
      Biomarker Screening.
AB  - High-density protein microarrays constitute a promising high-throughput platform
      for the characterization of protein expression patterns, biomarker discovery, and
      validation. Different types of protein microarrays have been described according
      to several features (such as content, format, and detection system) presenting
      advantages and disadvantages which are relevant for the specific application and
      purposes. Therefore, an experimental design is key for any screening based on
      protein microarrays assays; in fact, the data analysis strategy is directly
      related to the experimental design, type of protein microarray and consequently
      the final outcome, the data and results interpretation, is also directly linked.
      Here, it is proposed a systematic workflow for biomarker discovery based on
      tailor-made protein microarrays platforms which obtain comprehensively info for
      the functional protein characterization in high-throughput format.

PMID- 30276736
TI  - Metaproteomics Study of the Gut Microbiome.
AB  - Proteomics is a widely used method for defining the protein composition of a
      complex sample. As this approach allows for identification and quantification of
      proteins across a broad dynamic range as well as detection of post-translational
      modifications, proteomics is an ideal platform to investigate the gut microbiome
      at a functional level. The gut microbiome is a dynamic environment which is
      crucial for overall health and fitness. Imbalances in the gut microbiome can
      influence nutrient absorption, pathogen resistance, inflammation, and various
      human diseases. Metaproteomic analysis of the gut microbiome is currently being
      performed on bacteria isolated from (1) fecal samples (2) colonic lavage, or (3)
      colon biopsies. Investigation of the gut microbiome has demonstrated that within
      the colon, there are distinct communities based on spatial location, and
      separable from the gut microbiomes isolated from stool. In addition to expanding
      our understanding of host-bacterial interactions for human health and disease,
      gut microbiome analysis is being utilized for biomarker development to
      discriminate normal individuals and diseased (i.e., inflammatory bowel disease or
      colon cancer) patients as well as to monitor disease activity and prognosis.

PMID- 30276737
TI  - Double One-Dimensional Electrophoresis (D1-DE) Adapted for Immunoproteomics.
AB  - The classical proteomics approach for the identification of allergen candidates
      consists on the separation of proteins by high-resolution two-dimensional
      electrophoresis (2-DE) with subsequent IgE immunoblotting and further analysis of
      IgE-reactive protein spots with mass spectrometry. In this approach at least two
      gels most be run. One gel is used for staining and the other is for
      immunoblotting by antibodies labeled with specific immunostains. Additional
      functional characterizations require either protein purification or 2-DE
      replicates and appear to be time- and reagent-consuming. Here we described a
      modified double one-dimensional electrophoresis (D1-DE) allowing the conversion
      of a protein spot previously visualized by 2-DE into an extended protein band. In
      D1-DE, the purity of the protein of interest is similar to 2-DE spots, but its
      abundance is many times higher than what can be found in a 2-DE single spot
      allowing many other functional analyses from a single D1-DE separation.

PMID- 30276738
TI  - BioID: A Proximity-Dependent Labeling Approach in Proteomics Study.
AB  - Biological activities are mainly executed by proteins and in most of the
      occasions these activities are accomplished by protein complexes or through
      protein-protein interactions (PPI). So it is critical to reveal how the protein
      complexes are organized and demonstrate the PPIs involved in the biological
      processes. In addition to the traditional biochemical approaches, proximity
      dependent labeling (PDL) has recently been proposed to identify the interacting
      partners of a given protein. PDL requires the fusion expression of the target
      protein with an enzyme which catalyzes the attachment of a reactive molecule to
      the interacting partners in a distance-dependent manner. Further analysis of all
      the proteins that are modified by the reactive molecule discloses the identity of
      these proteins which are presumed to be interacting partners of the target
      protein. BioID is one of those representative PDL methods with the most widely
      applications. The enzyme used in BioID is a biotin ligase BirA which catalyzes
      the biotinylation of target protein with the presence of biotin. Through
      streptavidin-mediated pull-down and mass spectrometry analysis, the interacting
      protein candidates of a given protein can be obtained.

PMID- 30276739
TI  - Functional Application of Snake Venom Proteomics in In Vivo Antivenom Assessment.
AB  - Reverse-phase high-performance liquid chromatography is commonly employed as a
      decomplexing strategy in snake venom proteomics. The chromatographic fractions
      often contain relatively pure toxins that can be assessed functionally for
      toxicity level through the determination of their median lethal doses (LD50).
      Further, antivenom efficacy can be evaluated specifically against these venom
      fractions to understand the limitation of the antivenom as the treatment for
      snake envenomation. However, methods of toxicity assessment and antivenom
      evaluation vary across laboratories; hence there is a need to standardize the
      protocols and parameters, in particular those related to the neutralizing
      efficacy of antivenom. This chapter outlines the important in vivo techniques and
      data interpretation that can be applied in the functional study of snake venom
      proteomes.

PMID- 30276740
TI  - Proteomic Detection of Carbohydrate-Active Enzymes (CAZymes) in Microbial
      Secretomes.
AB  - Secretomes from microorganisms growing on biomass contain carbohydrate-active
      enzymes (CAZymes) of potential biotechnological interest. By analyzing such
      secretomes, we may discover key enzymes involved in degradation processes and
      potentially infer the mode-of-action of biomass conversion. Some of these enzymes
      may have predicted functions in carbohydrate degradation, while others may not,
      while yet exhibiting a similar expression pattern; these latter enzymes
      constitute potential novel enzymes involved in the degradation process and
      provide a basis for further biochemical exploration. Hence, secretomes represent
      an important source for the study of both predicted and novel CAZymes. Here we
      describe a plate-based culturing technique that allows for collection of protein
      fractions that are highly enriched for secreted proteins, bound or unbound to the
      substrate, and which minimizes contamination by intracellular proteins trough
      unwanted cell lysis.

PMID- 30276741
TI  - An Overview of Mass Spectrometry-Based Methods for Functional Proteomics.
AB  - The mechanism underlying many biological phenotypes remains unknown despite the
      increasing availability of whole genome and transcriptome sequencing. Direct
      measurement of changes in protein expression is an attractive alternative and has
      the potential to reveal novel processes. Mass spectrometry has become the
      standard method for proteomics, allowing both the confident identification and
      quantification of thousands of proteins from biological samples. In this review,
      mass spectrometry-based proteomic methods and their applications are described.

PMID- 30276742
TI  - Functional Proteomic Analysis to Characterize Signaling Crosstalk.
AB  - The biological activities of a cell are determined by its response to external
      stimuli. The signals are transduced from either intracellular or extracellular
      milieu through networks of multi-protein complexes and post-translational
      modifications of proteins (PTMs). Most PTMs including phosphorylation,
      acetylation, ubiquitination, and SUMOylation, among others, modulate activities
      of proteins and regulate biological processes such as proliferation,
      differentiation, as well as host pathogen interaction. Conventionally, reverse
      genetics analysis and single molecule-based studies were employed to identify and
      characterize the function of PTMs and enzyme-substrate networks regulated by
      them. With the advent of high-throughput technologies, it is now possible to
      identify and quantify thousands of PTM sites in a single experiment. Here, we
      discuss recent advances in enrichment strategies of various PTMs. We also
      describe a method for the identification and relative quantitation of proteins
      using a tandem mass tag labeling approach combined with serial enrichment of
      phosphorylation, acetylation and succinylation using antibody enrichment
      strategy.

PMID- 30276743
TI  - Identification of Unexpected Protein Modifications by Mass Spectrometry-Based
      Proteomics.
AB  - Peptide identification relies in the majority of mass spectrometry-based
      proteomics experiments on matching of experimental data against peptide and
      fragment ion masses derived from in silico digests of protein databases. One of
      the main drawbacks of this approach is that modifications have to be defined for
      database searching and therefore no unexpected modifications can be identified in
      a standard setup. Consequently, in many bottom-up proteomics experiments,
      unexpected modifications are not identified, even if high-quality fragment ion
      spectra of the modified peptides were acquired. It is therefore often not
      straightforward to identify unexpected modifications. In this protocol, we
      describe a stepwise procedure to identify unexpected modifications at peptides
      using the database search algorithm Mascot. The workflow includes parallel
      searches for the identification of known modifications at unexpected amino acids,
      error tolerant searches for modifications unexpected in the sample but known to
      the community, and mass tolerant searches for entirely unknown modifications.
      Furthermore, we suggest a follow-up strategy consisting of (1) verification of
      identified modifications in the initial dataset and (2) targeted experiments
      using synthetic peptides.

PMID- 30276744
TI  - Label-Free LC-MS/MS Strategy for Comprehensive Proteomic Profiling of Human
      Islets Collected Using Laser Capture Microdissection from Frozen Pancreata.
AB  - Diabetes mellitus is caused by either loss of pancreatic islets beta-cells (Type
      1 Diabetes, T1D), insufficient insulin release in the islet beta-cells coupled
      with insulin resistance in target tissues (Type 2 Diabetes, T2D), or impaired
      insulin release (genetic forms of diabetes and, possibly, T1D subtypes). The
      investigation of the islet proteome could elucidate facets of the pathogenesis of
      diabetes. Enzymatically isolated and cultured (EIC) islets are frequently used to
      investigate biochemical signaling pathways that could trigger beta-cell changes
      and death in diabetes. However, they cannot fully reflect the natural protein
      composition and disease process of in vivo islets due to the stress from
      isolation procedures and in vitro culture. The laser capture microdissection
      method employs a high-energy laser source to separate the desired cells from the
      remaining tissue section in an environment which is well conserved and close to
      the natural condition. Here, we describe a label-free proteomic workflow of laser
      capture microdissected (LCM) human islets from fresh-frozen pancreas sections of
      cadaveric donors to obtain an accurate and unbiased profile of the pancreatic
      islet proteome. The workflow includes preparation of frozen tissue section,
      staining and dehydration, LCM islets collection, islet protein digestion, label
      free Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), database search,
      and statistical analysis.

PMID- 30276745
TI  - Targeted Proteomics.
AB  - Targeted proteomics detects proteins of interest with high sensitivity,
      quantitative accuracy, and reproducibility. In a targeted proteomics assay,
      surrogate peptides are generated by proteolytic digestion of target proteins and
      selected reaction monitoring (SRM) assays are developed to quantify these
      peptides using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this
      report, we describe the details of quantitative analysis of target protein in
      cells and tissue samples.

PMID- 30276746
TI  - Metabolomic Investigation of Staphylococcus aureus Antibiotic Susceptibility by
      Liquid Chromatography Coupled to High-Resolution Mass Spectrometry.
AB  - Staphylococcus aureus is a major human pathogen that can readily acquire
      antibiotic resistance. For instance, methicillin-resistant S. aureus represents a
      major cause of hospital- and community-acquired bacterial infections. In this
      chapter, we first provide a detailed protocol for obtaining unbiased and
      reproducible S. aureus metabolic profiles. The resulting intracellular metabolome
      is then analyzed in an untargeted manner by using both hydrophilic interaction
      liquid chromatography and pentafluorophenyl-propyl columns coupled to high
      resolution mass spectrometry. Such analyses are done in conjunction with our in
      house spectral database to identify with high confidence as many meaningful S.
      aureus metabolites as possible. Under these conditions, we can routinely monitor
      more than 200 annotated S. aureus metabolites. We also indicate how this protocol
      can be used to investigate the metabolic differences between methicillin
      resistant and susceptible strains.

PMID- 30276747
TI  - Nuts and Bolts of Protein Quantification by Online Trypsin Digestion Coupled LC
      MS/MS Analysis.
AB  - Protein digestion coupled to liquid chromatography and tandem mass spectrometry
      (LC-MS/MS) detection enables multiplexed quantification of proteins in complex
      biological matrices. However, the reproducibility of enzymatic digestion of
      proteins to produce proteotypic target peptides is a major limiting factor of
      assay precision. Online digestion using immobilized trypsin addresses this
      problem through precise control of digestion conditions and time. Because online
      digestion is typically for a short time, the potential for peptide degradation, a
      major source of measurement bias, is significantly reduced. Online proteolysis
      requires minimal sample preparation and is easily coupled to LC-MS/MS systems,
      further reducing potential method variability. We describe herein a method
      optimized for the multiplexed quantification of several apolipoproteins in human
      serum using on-column digestion. We highlight key features of the method that
      enhance assay accuracy and precision. These include the use of value-assigned
      serum as calibrators and stable isotope-labeled (SIL) peptide analogs as internal
      standards. We also comment on practical aspects of column switching valve design,
      instrument maintenance, tandem mass spectrometry data acquisition, and data
      processing.

PMID- 30276748
TI  - Proteases: Pivot Points in Functional Proteomics.
AB  - Proteases drive the life cycle of all proteins, ensuring the transportation and
      activation of newly minted, would-be proteins into their functional form while
      recycling spent or unneeded proteins. Far from their image as engines of protein
      digestion, proteases play fundamental roles in basic physiology and regulation at
      multiple levels of systems biology. Proteases are intimately associated with
      disease and modulation of proteolytic activity is the presumed target for
      successful therapeutics. "Proteases: Pivot Points in Functional Proteomics"
      examines the crucial roles of proteolysis across a wide range of physiological
      processes and diseases. The existing and potential impacts of proteolysis-related
      activity on drug and biomarker development are presented in detail. All told the
      decisive roles of proteases in four major categories comprising 23 separate
      subcategories are addressed. Within this construct, 15 sets of subject-specific,
      tabulated data are presented that include identification of proteases, protease
      inhibitors, substrates, and their actions. Said data are derived from and
      confirmed by over 300 references. Cross comparison of datasets indicates that
      proteases, their inhibitors/promoters and substrates intersect over a range of
      physiological processes and diseases, both chronic and pathogenic. Indeed,
      "Proteases: Pivot Points ..." closes by dramatizing this very point through
      association of (pro)Thrombin and Fibrin(ogen) with: hemostasis, innate immunity,
      cardiovascular and metabolic disease, cancer, neurodegeneration, and bacterial
      self-defense.

PMID- 30276749
TI  - The Use of Combinatorial Hexapeptide Ligand Library (CPLL) in Allergomics.
AB  - The recent progress of proteomic protocols led to more efficient protein
      extraction and concentration procedures to remove nonprotein interfering
      compounds present in the starting material and to increase the concentration of
      underrepresented proteins. Combinatorial hexapeptide ligand libraries (CPLL) were
      recently applied to both plant- and animal-derived tissues for capturing the low-
      and very low-abundance allergens. Several IgE-binding proteins which were
      previously absent or poorly represented by using conventional proteomics tools
      have been detected and characterized through a CPLL-based approach. In the
      present chapter, a protocol based on improved protein extraction and enrichment
      by CPLL, allowing the immunochemical characterization of several "hidden
      allergens" in cypress pollen, is described in detail.

PMID- 30276750
TI  - Efficient Extraction and Digestion of Gluten Proteins.
AB  - Coeliac disease (CD) is a T-cell mediated autoimmune disorder triggered by
      ingestion of cereal gluten found in wheat (gliadins and glutenins), barley
      (hordeins), and rye (secalins). As the only treatment for CD is a lifelong gluten
      free diet, the measurement of gluten in raw ingredients and processed food
      products is critical to protecting people with CD or gluten intolerance. The most
      commonly employed method is the enzyme-linked immunosorbent assay (ELISA), but
      more recently mass spectrometry has been employed wherein the extracted gluten
      proteins are digested to peptides that are then directly measured. To achieve the
      goal of accurate gluten quantitation, gluten must be efficiently extracted from
      the ingredient or food matrix and then digested to yield the peptides that are
      monitored by LC-MS. In this chapter, a rapid, simple, and reproducible protocol
      for extraction and digestion of gluten proteins is described.

PMID- 30276751
TI  - Glycosylation Profiling of Tumor Marker in Plasma Using Bead-Based Immunoassay.
AB  - As one of the most important posttranslational modifications, glycosylation plays
      critical roles in protein folding, trafficking, cell differentiation, immune
      recognition, etc. The alteration of glycosylation is closely associated with the
      pathological processes during and after caner development, and thus holds great
      value in cancer detection. In this chapter, we describe a protocol on the
      glycosylation profiling of tumor marker in plasma using bead-based immunoassay
      with CA125 as a model, including bead coupling, coupling control, glycosylation
      assay, as well as the plasma screening for breast cancer patients. This protocol
      can be used to profile the glycosylation of protein markers in clinical plasma or
      serum samples for different human cancers.

PMID- 30276752
TI  - Protein-Specific Analysis of Invertebrate Glycoproteins.
AB  - N-Glycans are posttranslational modifications of proteins attached to the amide
      side chains of asparagine residues, with possible heterogeneity due to different
      structures being possible at the same glycosylation site. In contrast to the
      mammalian systems, invertebrate N-glycosylation presents a challenge in analysis
      as there exist unfamiliar epitopes and a high degree of structural and isomeric
      variation between different species. A simple analytical approach to analyze N
      glycans on specific glycoproteins is presented, which involves a combination of
      tryptic peptide mass spectrometry and "off-line" RP-HPLC MALDI-TOF MS/MS
      complemented by blotting to recognize specific epitopes. An additional N-glycan
      enrichment and labeling step can facilitate the analysis of single structures and
      even provide isomeric separation of N-glycans from specific proteins.

PMID- 30276753
TI  - The Use of Proteomics Studies in Identifying Moonlighting Proteins.
AB  - Proteomics studies that characterize hundreds or thousands of proteins in
      parallel can play an important part in the identification of moonlighting
      proteins, proteins that perform two or more distinct and physiologically relevant
      biochemical or biophysical functions. Functional assays, including ligand-binding
      assays, can find a surprising second function for a protein that was previously
      identified as performing a different function, for example, a DNA-binding ability
      for an enzyme in amino acid metabolism. The results of large-scale assays of
      protein-protein interactions, gene knockouts, or subcellular protein
      localizations, or bioinformatics analysis of amino acid sequences and three
      dimensional structures, can also be used to predict that a protein has additional
      functions, but in these cases it is important to use biochemical and biophysical
      methods to confirm the protein can perform each function.

PMID- 30276754
TI  - Two-Dimensional Biochemical Purification for Global Proteomic Analysis of
      Macromolecular Protein Complexes.
AB  - A high-resolution two-dimensional (2-D) proteomic fractionation technique for the
      systematic purification and subsequent mass spectrometry-based identification of
      endogenous protein macromolecular complexes is described. The method hyphenates
      preparative isoelectric focusing (IEF) with mixed-bed ion exchange chromatography
      (IEX) to efficiently separate cell- or tissue- derived soluble protein mixtures,
      allowing for more effective and less biased physiochemical characterization of
      stable multiprotein assemblies. After comprehensive 2D fractionation of cell-free
      lysates, each fraction is subjected to quantitative tandem mass spectrometry
      (MS/MS) and subsequent computational analysis to map high-confidence protein
      protein interactions (PPIs). Herein, the experimental component (workflow
      protocols) for this global "interactome" network mapping platform is described.

PMID- 30276755
TI  - A Data Analysis Protocol for Quantitative Data-Independent Acquisition
      Proteomics.
AB  - Data-independent acquisition (DIA) mode of mass spectrometry, such as the SWATH
      MS technology, enables accurate and consistent measurement of proteins, which is
      crucial for comparative proteomics studies. However, there is lack of free and
      easy to implement data analysis protocols that can handle the different data
      processing steps from raw spectrum files to peptide intensity matrix and its
      downstream analysis. Here, we provide a data analysis protocol, named diatools,
      covering all these steps from spectral library building to differential
      expression analysis of DIA proteomics data. The data analysis tools used in this
      protocol are open source and the protocol is distributed at Docker Hub as a
      complete software environment that supports Linux, Windows, and macOS operating
      systems.

PMID- 30276756
TI  - Early detection of memory impairments in older adults: standardization of a short
      version of the verbal and nonverbal Recognition Memory Test.
AB  - In several neurological conditions, in elderly and cognitively impaired subjects,
      memory functioning must be evaluated to early detect the cognitive deterioration
      processes. In particular, recognition memory assessment is an essential step in
      the clinical and neuropsychological evaluation of early memory impairments. The
      Recognition Memory Test (RMT) developed by Smirni et al. (G Ital Psicol
      XXXVII(1):325-343, 2010) is an effective instrument to assess verbal and
      nonverbal recognition memory in the Italian population. The current study
      provides a new, brief, and reliable RMT format to evaluate recognition memory on
      elderly subjects and it reports normative data in an older adult Italian
      population sample (including 100 participants well distributed across sex,
      education, and age categories). The shortened version of RMT keeps the
      administration procedures and materials of the original Italian RMT constant,
      i.e., words, faces, and buildings. Multiple regression analysis revealed
      significant effects of age and educational level on performance but no effect of
      sex. Inferential cutoffs have been determined and equivalent scores computed. The
      availability of equivalent scores for the Recognition Memory Test will prove
      useful in the clinical evaluation of patients' memory profiles.

PMID- 30276757
TI  - Analyte-triggered cyclic autocatalytic oxidation amplification combined with an
      upconversion nanoparticle probe for fluorometric detection of copper(II).
AB  - The authors describe an upconversion nanoparticle-based (UCNP-based) fluorometric
      method for ultrasensitive and selective detection of Cu2+. The UCNPs show a
      strong emission band at 550 nm under near-infrared excitation at 980 nm. The
      principle of the strategy is that gold nanoparticles (AuNP) can quench the
      fluorescence of UCNP. In contrast, the addition of L-cysteine (Cys) can induce
      the aggregation of AuNP, resulting in a fluorescence recovery of the UCNPs. On
      addition of Cu2+, it oxidizes Cys to cystine and is reduced to Cu+. The Cu+
      thusformed can be oxidized cyclically to Cu2+ by dissolved O2, which catalyzes
      and recycles the whole reaction. Thus, the aggregation of AuNP is inhibited and
      the fluorescence recovered by Cys is quenched. Under the optimal condition, the
      quenching efficiency shows a good linear response to the concentrations of Cu2+
      in the 0.4-40 nM range. The limit of detection is 0.16 nM, which is 5 orders of
      magnitude lower than the U.S. Environmental Protection Agency limit for Cu2+ in
      drinking water (20 MUM). The method has been further applied to monitor Cu2+
      levels in real samples. The results of detection are well consistent with those
      obtained by atomic absorption spectroscopy. Graphical abstract Gold nanoparticles
      (AuNP) as a high efficient fluorescence quenching reagent of upconversion
      nanoparticles (UCNP) were used in a fluorometric method for detection of Cu2+
      based on a cyclic catalytic oxidation amplification strategy.

PMID- 30276758
TI  - Toxic Peptides in Populations of Two Pergid Sawflies, Potential Biocontrol Agents
      of Brazilian Peppertree.
AB  - Determination of the safety of agents prior to release is one of the most
      important research goals in biological control. In addition to concerns for the
      safety of non-target plants, determination of the potential toxic properties of
      new agents needs to be assessed. Numerous phytophagous insects are defended by
      chemicals against the attack of natural enemies. Some of these defensive
      compounds could pose an environmental risk if an agent is released. Here, larval
      populations of two pergid sawflies, Heteroperreyia hubrichi and H. jorgenseni,
      were analyzed by LC-MS/MS to investigate whether they contain alleged toxic
      peptides. The first species is a potential candidate for biological control of
      the invasive weed Brazilian peppertree in Florida and Hawaii. The chemical
      analyses revealed the presence of the peptides pergidin (Perg), 4-valinepergidin
      (VPerg), dephosphorylated pergidin (dpPerg), lophyrotomin (LGln and LGlu). The
      effect of sawfly population for each species was significantly influencing
      peptide concentration. All peptides occurred at lower concentrations compared
      with purportedly toxic species of this sawfly family. However, the concentrations
      of the peptides are of concern for the welfare of wildlife and livestock that
      would be exposed to these species. These results demonstrate that release of this
      biological control agent in the invaded range may pose an environmental threat.

PMID- 30276759
TI  - Efficacy of Huaier granule in patients with breast cancer.
AB  - BACKGROUND: Huaier extract has been demonstrated to exhibit potent anti-tumor
      effects in various types of cancer cells. However, the clinical benefit of Huaier
      granule in breast cancer has not been reported. In this study, we aimed to
      evaluate the efficacy of Huaier granule in breast cancer patients. METHODS: Our
      study included 284 breast cancer patients treated with or without Huaier granule
      between January 2005 and October 2016 at Qilu Hospital, Shandong University,
      Jinan, China. Retrospective data obtained included demographics,
      clinicopathological characteristics, disease-free survival (DFS), serum
      concentrations of tumor markers, the Karnofsky performance scale (KPS), and
      incidences of emotional symptoms. DFS was the main outcome measure. RESULTS: Of
      the patients included, 144 were classified into the control group and 140 into
      the Huaier group. Baseline characteristics were well balanced between the study
      arms. Median DFS was 91.43 months for control group and 112.61 months for Huaier
      group (hazard ratio (HR) = 2.97, 95% confidence interval (CI) = 1.57-5.61, p <
      0.01). After Huaier granule treatment, the serum levels of tumor markers could be
      reduced to the normal range. In addition, breast cancer patients with Huaier
      granule treatment had higher KPS scores and less emotional symptoms. CONCLUSIONS:
      Our data demonstrated that patients orally administrated Huaier granule got
      longer DFS. Furthermore, Huaier granule could reduce serum tumor markers, improve
      the functional status, and decrease the incidences of emotional symptoms in
      breast cancer patients. Therefore, Huaier granule was an effective therapy for
      women with breast cancer.

PMID- 30276760
TI  - Correction to: Do Limitations in the Design of PARADIGM-HF Justify the Slow Real
      World Uptake of Sacubitril/Valsartan (Entresto)?
AB  - The original version of this article unfortunately contained a mistake. There was
      a typo in the second sentence of the paragraph under the section Was the Dose of
      Drugs Fair?; "320 mg twice a day" should read "160mg twice a day". The corrected
      paragraph is shown below.

PMID- 30276761
TI  - Bio-artificial bone formation model with a radial-flow bioreactor for implant
      therapy-comparison between two cell culture carriers: porous hydroxyapatite and
      beta-tricalcium phosphate beads.
AB  - Bone grafting is necessary before dental implant treatment in patients with jaw
      bone defects. Currently, autologous bone grafting is a major burden on the
      patient. However, it is impossible to form a sufficient foundation for the
      implant with a bone-filling agent alone. It is, therefore, necessary to prepare
      hybrid artificial bone tissue containing osteoblasts and osteoclasts. In this
      study, mouse MC3T3-E1 pre-osteoblast cells and human embryonic-derived
      osteoblastic cell line hFOB1.19 were cultured in radial-flow bioreactors (RFB) to
      form three-dimensional artificial bone filled with porous beads of beta
      tricalcium phosphate (beta-TCP) or hydroxyapatite (HA)-which are clinically used
      as bone-filling agents-as cell culture carriers. When circulation culturing was
      performed in the growth medium for the first 10-12 days, glucose consumption was
      increased in the cultures with HA beads in comparison to the cultures with beta
      TCP beads. When cultured in the differentiation culture medium during the second
      half of the culture period, the glucose consumption decreased in the culture with
      HA beads. A DNA microarray analysis suggested that osteogenesis progressed fast
      in three-dimensional culture filled with HA beads and that partly differentiation
      into osteoblasts was prominent in cultures with beta-TCP beads. In the growth
      process of MC3T3-E1 cells, the vitamin A metabolism was also activated, the
      synthesis and degradation of retinoic acid was enhanced, and the metabolism of
      the same process decreased at the end of differentiation in three-dimensional
      cultures. Three-dimensional circulation culture in RFB is considered to be useful
      for the formation of hybrid bio-artificial bone tissue.

PMID- 30276762
TI  - TRK Inhibition: A New Tumor-Agnostic Treatment Strategy.
AB  - Oncogenic somatic chromosomal rearrangements involving the NTRK1, NTRK2 or NTRK3
      genes (NTRK gene fusions) occur in up to 1% of all solid tumors, and have been
      reported across a wide range of tumor types. The fusion proteins encoded by such
      rearranged sequences have constitutively activated TRK tyrosine kinase domains,
      providing novel therapeutic anticancer targets. The potential clinical
      effectiveness of TRK inhibition in patients with tumors harboring NTRK gene
      fusions is being assessed in phase I and II trials of TRK inhibitors, such as
      larotrectinib and entrectinib. Clinical trial results have demonstrated that
      larotrectinib is generally well tolerated and has shown high response rates that
      are durable across tumor types. These data validate NTRK gene fusions as
      actionable genomic alterations. In this review, we present the clinical data,
      discuss the different approaches that might be used to routinely screen tumors to
      indicate the presence of NTRK gene fusions, explore the issue of acquired
      resistance to TRK inhibition, and reflect on the wider regulatory considerations
      for tumor site agnostic TRK inhibitor drug development.

PMID- 30276763
TI  - Sustained prognostic impact of circulating tumor cell status and kinetics upon
      further progression of metastatic breast cancer.
AB  - PURPOSE: Serial longitudinal enumeration of circulating tumor cells (CTCs) has
      shown its prognostic value on progression-free survival and overall survival (OS)
      in patients with stage IV breast cancer. This study prospectively evaluated the
      role of CTCs as a prognostic marker during further progression of metastatic
      breast cancer (MBC). METHODS: Among 476 MBC patients recruited between 2010 and
      2015, the 103 patients with a known CTC status at baseline (CTCBL) and within 4
      weeks of tumor progression (CTCPD) were included. Progressive disease (PD) was
      defined according to the Response Evaluation Criteria in Solid Tumors (RECIST,
      version 1.1). Using the CellSearch method, < 5 and >= 5 CTCs per 7.5 ml blood
      were determined as negative and positive, respectively. A shift in CTC status
      from baseline to progression ([Formula: see text] to [Formula: see text] and vice
      versa) was considered as alternating KineticsBL-PD. RESULTS: Median follow-up was
      29.9 [21.2, 40.0] months. CTCPD positivity (37%, n = 38) was associated with a
      significantly shorter OS than CTCPD negativity (8.0 [5.1, 10.9] vs 22.6 [15.3,
      39.8] months; P < 0.001). Alternating KineticsBL-PD was observed in 24% of the
      patients. This significantly changed the OS prediction of [Formula: see text]
      patients ([Formula: see text] vs [Formula: see text], 11.4 [9.7, not available
      (NA)] vs. 7.6 [4.4, 11.5] months; P = 0.044) and [Formula: see text] patients
      ([Formula: see text] vs. [Formula: see text], 8.4 [4.0, NA] vs. 22.6 [18.9, NA]
      months, respectively; P < 0.001). Prediction of survival was significantly
      improved (P = 0.002) by adding CTCPD status to clinicopathological
      characteristics and CTCBL status. CONCLUSIONS: CTC status upon further disease
      progression is a prognostic factor that could significantly improve well
      established models. Thus, it represents a potential additional instrument
      supporting treatment decision.

PMID- 30276764
TI  - Prediction of Schizophrenia Diagnosis by Integration of Genetically Correlated
      Conditions and Traits.
AB  - Schizophrenia is genetically heterogeneous and comorbid with many conditions. In
      this study, we explored polygenic scores (PGSs) from genetically related
      conditions and traits to predict schizophrenia diagnosis using both logistic
      regression and deep neural network (DNN) models. We used the combined Molecular
      Genetics of Schizophrenia and Swedish Schizophrenia Case Control Study (MGS +
      SSCCS) data for training and testing the models, and used the Clinical
      Antipsychotic Trials for Intervention Effectiveness (CATIE) data as independent
      validation. We screened 28 conditions and traits comorbid with schizophrenia to
      identify traits as potential predictors and used LASSO regression to select
      predictors for model construction. We investigated how PGS calculation influenced
      model performance. We found that the inclusion of comorbid traits improved model
      performance and PGSs calculated from two traits were more generalizable in
      independent validation. With a DNN model using 19 PGS predictors, we accomplished
      a prediction accuracy of 0.813 and an AUC of 0.905 in the MGS + SSCCS data. When
      this model was validated with the CATIE data, it achieved an accuracy of 0.721
      and AUC of 0.747. Our results indicate that PGSs alone may not be sufficient to
      predict schizophrenia accurately and the inclusion of behavioral and clinical
      data may be necessary for more accurate prediction model.

PMID- 30276766
TI  - [Health Without Boundaries].
AB  - 'Sow in spring, grow through the summer, harvest in autumn, store in winter'
      reflects the ancient wisdom of the Chinese people, passed down for thousands of
      years. As this year comes to a close, this journal would like to pause to
      recognize that Taiwan's national health insurance system has been looking after
      and caring for the health of Taiwan's people for more than 20 years. What can we
      do to better follow global care trends and to perform better for public health in
      Taiwan? Many thanks to Director Wang of the Health Promotion Administration for
      introducing to readers the concept of 'health without boundaries' and examining
      Taiwan's future healthcare blueprint from a global perspective. In addition,
      under the influence of fast-changing medical technologies and rising life
      expectancies, the increase in the population with chronic diseases prompted
      Health Promotion Administration's Chronic Disease Division Chief Jia Shuli to
      provide a comprehensive description of his division's work, from developing
      chronic disease self-care regimens to developing follow-up control protocols.
      Professor Lin, with years of diabetes prevention, treatment and innovative
      experience, has also written an article for this issue that explains why health
      professionals should go beyond dealing with diseases in order to listen,
      cooperate with, and interact with patients in order to expand the adoption and
      effectiveness of diabetes self-management programs. Finally, Professor Guo's
      article stresses the importance of promoting a healthy environment by going
      beyond focusing on one's health to address the improvement of the overall
      environment in order to shape the urban health landscape and achieve A+ health
      quality. In these cold winter days, brew a pot of hot tea and let us taste
      together these rare journeys of wisdom.

PMID- 30276765
TI  - Distal pancreatectomy with autologous islet transplantation in chronic
      pancreatitis patients: First case series from India.
AB  - Pancreatectomy and autologous islet transplantation (AIT) are performed in highly
      specialized centers to alleviate abdominal pain and preserve endocrine function
      in patients with chronic pancreatitis. We aimed at initiating AIT studies in
      India for the first time in patients undergoing distal pancreatectomy (DP) to
      prevent development of diabetes. Four out of 14 chronic pancreatitis patients
      screened underwent DP with AIT. Pancreatectomy specimen preserved in Wisconsin
      solution was subjected to islet isolation employing standard protocol using
      collagenase V. Isolated islets were infused into the liver through portal vein
      after quality assessment and the four patients were followed for 1 year. During
      the study period, blood glucose, fasting insulin, and C-peptide were analyzed and
      glucose tolerance was assessed. Three patients could be infused with islets (4363
      Islet equivalents, IEQ/kg, 3860 IEQ/kg, 3600 IEQ/kg) into liver without any
      infusion-related complications. Two of these patients maintained glucose
      tolerance and glycemic control (HbA1c: 6.0%) and one became diabetic at the end
      of 1 year (HbA1c: 7.5%). Circulating fasting insulin increased (2.7-24.4 MUU/mL
      and 4.0-21.2 MUU/mL) and C-peptide levels increased (2.2 to 3.6, 3.4-5.6 ng/mL)
      in these two patients. Circulating insulin was 2.7 MUU/mL and C-peptide was 2.4
      ng/mL in the patient who became diabetic at the end of 1 year, while insulin was
      2.3 MUU/mL and C-peptide was 1.2 ng/mL in the patient who could not be infused
      with islets after DP. Safety and feasibility of autologous islet transplantation
      is established in India for the first time.

PMID- 30276767
TI  - [Health Promotion Policies for All in Taiwan].
AB  - Health promotion was defined at the first International Conference on Health
      Promotion held by the World Health Organization in 1986 as a process that enables
      the public to improve their health. Moreover, the United Nations High-Level
      Meeting on the Prevention and Control of Non-Communicable Diseases in 2011
      highlighted that non-communicable diseases (NCDs) account for 63% of deaths
      worldwide, with major NCD-related risk behaviors including tobacco use, physical
      inactivity, the harmful use of alcohol, and unhealthy diet. In 2013, the WHO
      announced the Global Action Plan for the Prevention and Control of NCDs 2013
      2020, with the United Nations listing NCDs prevention and control as a major
      topic for nations in Sustainable Development Goal 3 (Health). Both Taiwan and the
      world face the dual threats of population aging and NCDs, adding to the
      importance of health promotion and NCDs prevention and control. This article
      first introduces the relevant global health trends and the corresponding status
      of Taiwan and then examines the major NCDs prevention and health promotion
      policies in Taiwan. In creating a health-supportive environment for all people
      and enhancing health literacy and empowerment among the general public, we hope
      to ensure that every individual, family, and city joins the ongoing effort in
      Taiwan to enable all individuals to make the best, informed decisions for their
      health.

PMID- 30276768
TI  - [Chronic Disease Prevention: Present and Future].
AB  - Non-communicable diseases (NCDs) have risen to become a major threat to health
      worldwide. According to the World Health Organization, NCDs accounted for 68% of
      all global mortality in 2014, with over 40% of NCD-related mortality incidents
      defined as premature deaths under the age of 70 years. Among the top-10 causes of
      death named by the Taiwan Ministry of Health and Welfare in 2017, 28% were
      cancers, 22.3% were cardiovascular diseases, 5.7% were diabetes, and 3.6% were
      chronic obstructive pulmonary diseases. These four major NCDs currently account
      for nearly 60% of all mortalities in Taiwan and reflect the threat of NCDs to
      global health. Taiwan's increasingly ageing society faces an increasing risk of
      NCDs, which threatens the health and wellbeing of Taiwan's population. A survey
      by the Health Promotion Administration in 2013 found that over 80% of senior
      citizens in Taiwan are afflicted with one or more NCD and that the presence of a
      comorbidity further exacerbates the problem of living and coping with NCDs. This
      article introduces the primary, secondary, and tertiary public health prevention
      measures related to NCDs in order to help caregivers better understand the
      importance of reducing the risk factors of NCDs and of screening to promote early
      detection and treatment. This article further proposes a systemic framework for
      the future care of NCDs.

PMID- 30276769
TI  - [From Monologue to Dialogue: The Evolution of Diabetes Self-Management
      Education].
AB  - Diabetes is a chronic disease. Patients with diabetes must actively change their
      eating and exercise habits and cannot rely solely on medication. Moreover, these
      patients need to control high blood glucose, high blood pressure, and high blood
      cholesterol, commonly known as control of the "three highs". As the current state
      of diabetes control is not ideal in the United States and Taiwan, disease-related
      complications such as blindness and the need for dialysis is expected to continue
      to increase in these countries in the future. This article highlights the
      possible factors of poor control of the "three highs" such as the therapeutic
      inertia of physicians (also known as clinical inertia), patient adherence, and
      current challenges in diabetes self-management education. In the past, courses in
      health education at our institution have been frequently delivered in monologue
      format. In recent years, we have tried a form of group therapy known as shared
      medical appointment (SMA) in order to encourage dialogue among patients and
      minimize didactic teaching. The preliminary results have been promising. In
      recent weeks, we began to discuss targeting SMA therapy on the topics of food
      metabolism and the typical effects and side effects of new and old drugs. We hope
      this will ease our introduction of shared decision making (SDM) in the near
      future. Promoting time-consuming procedures such as SDM is difficult in Taiwan
      because national-insurance health insurance payments to the healthcare provider
      are based on volume rather than value. We hope that the Health Insurance Bureau
      begins to recognize and appreciate the contribution of nurse educators and
      dietitians in the care of patients with diabetes and approve compensation for
      their hard work.

PMID- 30276770
TI  - [Health Without Borders: Creating Healthy Cities].
AB  - Urbanization, a rapidly rising trend worldwide, is being felt particularly
      strongly in East Asia. The World Health Organization (WHO) launched a healthy
      cities plan in 1986 as a platform to encourage cities around the world to
      eliminate the problems resulting from increasingly dense urban population
      densities. The health and quality of life of city residents are seriously
      affected by the problems associated with urbanization, including environmental
      pollution, traffic congestion, public insecurity, and inadequate infrastructure,
      which may exceed the scope of local government plans and expectations. Rather
      than dealing with these problems individually, urban planners must take a global
      approach to issue of urbanization. Public and private-sector inputs are critical
      to facilitating good urban planning and community development by local
      governments in order to help cities achieve a well-managed urban environment that
      gives citizens a good environment in which to live, work, and play. The promotion
      healthy-city plans in Taiwan will foster the creation of cities of health through
      the integration or cooperation of government health, urban-planning,
      environmental-protection, industrial-development, transportation, cultural
      education, and other departments and agencies. Based on the vision of a healthy
      city, Taiwan's cities should gradually attain a sustainable, healthy society and
      healthy environment that promotes the holistic health of their residents.
      Therefore, we look forward to fulfilling the vision of "health without borders,
      creating healthy cities" through the implementation of the healthy city plan.

PMID- 30276771
TI  - [Chan-Chuang Qigong Improves Exercise Capacity, Depression, and Quality of Life
      in Patients With Heart Failure].
AB  - BACKGROUND: Evidence-based research has shown the effects of traditional Chinese
      exercise on exercise capacity, depression, and quality of life in patients with
      cardiovascular disease. However, the effects of Chan-Chuang qigong on the
      physical and psychological status and on the quality of life of these patients
      are unknown. PURPOSE: To investigate the effects of Chan-Chuang qigong on
      exercise capacity, depression, and quality of life in patients with heart
      failure. METHODS: A randomized controlled study with repeated measures was
      conducted. One hundred participants with heart failure were recruited from a
      teaching medical center in Taiwan. Permuted block randomization was used to
      randomly assign the participants to either the Chan-Chuang qigong group, which
      received Chan-Chuang qigong intervention for three-months, or the control group.
      The outcome variables included six-minute walk distance, depression, and quality
      of life. RESULTS: Generalized estimating equation analyses showed that the Chan
      Chuang qigong group achieved significantly greater improvements than the control
      group in terms of six-minute walk distance (p = .001, p < .001, p < .001,
      respectively) and quality of life (p = .016, p < .001, p < .001, respectively) at
      2, 4, and 12 weeks after the intervention and depression at 12 weeks after the
      intervention (p = .016). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results of
      this study indicate that Chan-Chuang qigong improves exercise capacity,
      depression, and quality of life in patients with heart failure without imposing
      harmful side effects.

PMID- 30276772
TI  - [The Relationship Between Diet Nutrition Knowledge and Demographic
      Characteristics in Family Caregivers of Patients With Dementia].
AB  - BACKGROUND: Although the general-care knowledge of family caregivers related to
      dementia had been studied, little attention has been given to understanding the
      knowledge of caregivers related to dementia diet nutrition. This knowledge is
      important to help caregivers handle the eating and nutrition problems of people
      with dementia (PwD). PURPOSE: The purpose of this study was to explore the
      dementia diet nutrition knowledge of family primary caregivers and to analyze
      whether demographic characteristics of caregivers and/or the dementia stages of
      PwD have a relationship with dementia diet nutrition knowledge. METHODS: A
      descriptive and cross-sectional study using a questionnaire survey was conducted.
      A total of 220 primary family caregivers of people with dementia were recruited.
      RESULTS: Results showed that the average total score for the 13 questions on diet
      nutrition knowledge was 71.85%. Moreover, only 28.2% of the participants answered
      the question "Malnutrition is a significant risk during the early stage of
      dementia" correctly. In addition, the findings showed significant differences in
      the diet nutrition knowledge of participants based on education level (F = 3.989,
      p < .05) and the use of foreign (non-Taiwanese) caregivers (t = -2.919, p < .01).
      CONCLUSIONS: The participants had sufficient overall diet nutrition knowledge of
      dementia. However, they lacked knowledge in specific areas. Family caregivers
      with higher levels of education and those who hired foreign caregivers had better
      knowledge scores. The results may be used as a reference for nurses providing
      dementia dietary education. It is recommended that special attention be given to
      dietary education when patients are at the early onset phase of the disease and
      when caregivers have a lower level of education in order to improve the overall
      quality of dementia dietary care in the community.

PMID- 30276773
TI  - [Exploring Resilience and Related Factors Among Patients With Stroke in the
      Recovery Stage].
AB  - BACKGROUND: Resilience is known to affect the degree to which individuals adapt
      to the impact of stroke and its sequelae. However, few studies have examined
      resilience and related factors among stroke patients in Taiwan. PURPOSE: To
      explore resilience and related factors among stroke patients in the recovery
      stage. METHODS: A cross-sectional and correlational study design was adopted.
      Convenience sampling was employed to recruit participants from the rehabilitation
      inpatient wards of a regional teaching hospital in northern Taiwan. A structured
      questionnaire, including the social support scale and the Chinese version of the
      resilience scale, was used for data collection. Data were analyzed using
      descriptive and inferential statistics and stepwise regression analysis. RESULTS:
      A total of 128 stroke recovery in-patients who averaged 57.2 +/- 11.6 years of
      age and were predominantly male were recruited. The results of this study showed
      that the global resilience of participants was moderate and that a significantly
      positive correlation existed between global social support and resilience. Age,
      marital status, and global tangible social support accounted for 25.0% of the
      total variation in resilience. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Age,
      marital status and global tangible social support were identified as the crucial
      predictive factors of resilience in stroke patients. The results support the
      recommendation that healthcare providers should acquire advanced knowledge and
      skills through in-service education, proactive caring, and encouraging patients
      to learn self-care in order to enhance rehabilitation motivation and confidence
      levels and subsequently promote disease recovery and the ability to adapt to life
      through cross-disciplinary medical team cooperation and supportive relationships.

PMID- 30276774
TI  - [Risk Factors of Retained Central Venous Catheter Associated Bloodstream
      Infections in Hospitalized Patients].
AB  - BACKGROUND: Despite recent efforts in Taiwan to reduce the risk and incidence of
      central venous catheter associated bloodstream infections (CABSI), the results as
      reported by the Taiwan Centers for Disease Control, when compared with the
      results achieved in the USA, indicate that Taiwan must promote the central venous
      catheter bundle approach more effectively. Furthermore, the risk factors for
      CABSI should be explored further in order to facilitate the development and
      implementation of effective related improvement strategies. PURPOSE: To explore
      the risk factors for CABSI after adjusting for confounding factors and to analyze
      the appropriate protocol for applying retained central venous catheters in
      hospitalized patients and the impact of CABSI. METHODS: The ethics committee
      approved this retrospective case-control study. Hospitalized patients who were
      older than 20 years of age and were currently experiencing their first instance
      of CABSI were recruited between March 1, 2014 to October 31, 2014 as the case
      group. In addition, a control group was recruited in a 1:2 ratio from a random
      sample of patients listed in the medical order system who had received a central
      venous catheter but did not experience CABSI. Anyone who did not meet the above
      criteria was excluded. Data collected included basic demographic characteristics,
      basic catheter information, and the main reason for the catheter being in situ
      during the 48 hours prior to contracting CABSI or catheter removal. RESULTS: A
      total of 65 patients with CABSI comprised the case group and 130 patients without
      CABSI comprised the control group. After controlling for potentially confounding
      factors using logistic regression analysis, the independent risk factors of CABSI
      (p < .05) were identified as: staying in the intensive care unit, having a high
      APACHE II (acute physiology and chronic health evaluation II) score, and having
      diabetes mellitus. Moreover, while having inappropriate central venous catheter
      in situ was found to not significantly influence CABSI (OR, 2.41; 95% CI [0.65
      8.91]), we identified that about 10.8% of retained central venous catheter
      applications were unnecessary due to the lack of sufficient indications for use.
      CONCLUSIONS: We recommend that nursing staffs should remind physicians to
      evaluate carefully the need to use central venous catheters and should fully
      implement sterile protocols to protect the health of high-risk patients. In
      addition, nursing staffs should assess the central venous catheter daily and
      should remind physicians to remove the catheter as soon as possible in the
      absence of indications for use.

PMID- 30276775
TI  - [Using the Facebook Social Networking Website to Improve the Utilization of
      Weight Loss Programs by Community Obese Adults].
AB  - BACKGROUND: In light of the known impacts of obesity on well-being, we regularly
      work to promote weight loss programs in community settings. However, we found
      that a gap exists between the need for weight loss and the utilization of healthy
      weight loss programs among BMI (body mass index) >= 27 kg/m2adults. The low
      utilization of healthy weight loss programs may lower the overall benefit of
      these programs. PURPOSE: We reexamined access to health services and developed an
      accessible weight loss program for BMI >= 27 kg/m2adults that would improve the
      overall utilization of healthy weight loss programs. RESOLUTION: A telephone
      survey for obese adults was conducted to explore the reasons that discouraged
      persons in this group to not use our weight loss programs. The main reasons
      identified were: program schedules did not fit with respondent's daily schedule,
      the unsuitable services provided, and the overly long distance to the weight loss
      class. The social-cognitive-theory-based 1-year weight loss program that was
      developed provided immediate and accurate information about weight loss,
      inspiring words, weight management advice, and immediate and convenient
      consultation services. Moreover, this program established an incentives system on
      a social networking platform (Facebook) and was marketed under a creative slogan.
      RESULTS: The developed weight loss program increased not only program utilization
      (from 54.7% to 78.1%) but also reduced the average weight of obese adult
      participants by 3.4 kg. CONCLUSIONS: Conclusions: This program adjusted existing
      weight loss programs and improved the utilization of weight loss programs. These
      results may be applied elsewhere to increase weight-loss efficacy and to maximize
      health.

PMID- 30276776
TI  - [Reducing Blood Culture Contamination Rates in the Emergency Department].
AB  - BACKGROUND: Rate of contamination is a well-known indicator of quality of care in
      the emergency department. Blood-culture results may affect clinical decision
      making. From January 1, 2015 to December 31, 2015, the contamination rate of
      blood culture in our emergency department was 5.63%, which exceeded the maximum
      of 3% suggested by the American Society for Microbiology and the clinical
      laboratory at our hospital. PURPOSE: Using a quality improvement strategy, this
      project aimed to (1) identify potential factors contributing to the high blood
      culture contamination rate and (2) achieve a blood culture contamination rate
      below 3%.  RESOLUTION : The factors that were identified as potentially
      contributing to the high blood culture contamination rate were: (a) Nursing
      staff: lack of related education and training and ignorance of related clinical
      guidelines; (b) The system: inconsistent and non-evidence-based clinical
      guidelines (e.g., no requirement to use sterile gloves when obtaining blood
      cultures and changing disinfectants); (c) The patient: older patients, residents
      of long-term care facility, and patients whose blood culture were in the first
      set were associated with higher blood culture contamination rates. Our quality
      improvement strategy included: design a new bedside working plate, develop
      slogans and posters illustrating the proper blood-drawing procedure, make a video
      introducing current standard technology, provide continuing education, monitor
      contamination rates, and provide individual feedback and retraining for those
      with higher contamination rates. RESULTS: The strategy was implemented from
      October 1, 2016 to December 31, 2016, during which period the blood culture
      contamination rate reduced from 5.63% to 1.51%. CONCLUSIONS: Conclusion:
      Improving equipment, using multiple teaching methods, and providing regular
      feedback not only significantly reduced the blood culture contamination rate but
      also enhanced the knowledge and skills of nursing staff in terms of blood culture
      sampling. We hope that our results are referenced by other nursing departments
      and used to improve the blood culture contamination rates in other clinical
      settings.

PMID- 30276777
TI  - [Applying the Concept of Grief Counseling in Caring for an Elderly Dialysis
      Patient With Bereavement Due to the Death of Spouse: A Nursing Care Experience].
AB  - This article describes a 76-year-old dialysis patient who experienced widowhood.
      The nursing intervention occurred between April 2nd to June 28th, 2015. Using
      observation, interviews, medical records and health examinations, the authors
      assessed the patient's physical, psychological, social, intellectual, and
      spiritual status. The patient not only presented poor appetite, insomnia,
      hopelessness, and grief but had also attempted suicide. Thus, three health
      problems were identified, including dysfunctional grieving, hopelessness, and
      sleep pattern disturbance. Employing caring, active listening, and empathy, we
      helped the patient achieve the four tasks of Worden's Mourning: (1) to accept the
      reality of loss; (2) to work through the pain of grief; (3) to adjust to an
      environment in which the deceased is missing; and (4) to emotionally relocate the
      deceased and move on with life. With comprehensive and persistent nursing
      intervention, the patient got the support from her family members and eventually
      readapted to life without the deceased and continued to take hemodialysis and
      found new life motivation.

PMID- 30276778
TI  - [An Experience Providing Hospice Care to a Terminal Cancer Patient].
AB  - This study discusses a case in which corneal-donation care was provided to a 57
      year-old patient with terminal salivary gland cancer. Nursing care was provided
      from June 1 to June 28, 2017. The overall nursing assessment (covering
      physiological, psychological, social, and spiritual aspects) confirmed that the
      three main issues faced by the patient were chronic pain, dysfunctional family
      processes, and spiritual disturbances. Effective pain treatment was applied
      during the care process in order to stabilize the patient's physical condition. A
      hospice shared care team then worked together to help the patient mend his
      relationships with family members, fulfill his wish to donate his cornea, find
      meaning in his life, affirm his contribution to his family and society, and die a
      peaceful death. With regard to clinical practice, an explanation of corneal
      donation should be included in the conventional educational guidelines for
      hospice care. In addition to referrals to the relevant medical teams, it is
      recommended that nursing personnel who deal with patients like this participate
      in organ donation courses and develop positive attitudes and grief counseling
      skills. These actions will enable them to build up the professionalism,
      confidence, patience, and organ procurement-related skills required for the
      provision of care to these patients, which will in turn lead to better-quality
      palliative care. It is hoped that the nursing experience shared herein provides
      nursing personnel with a reference for palliative cancer care.

PMID- 30276779
TI  - [Nursing Experience With Reconstructing Self-Control Using Rational-Emotive
      Behavior Therapy on a Patient With Schizophrenia and Obsessive-Compulsive
      Symptoms].
AB  - This case report describes a nursing experience caring for a patient with
      schizophrenia and obsessive-compulsive symptoms. This patient suffered from
      symptoms of being controlled, obsessive thoughts, and compulsive behaviors. In
      addition, the patient showed no interest in implementing strategies for dealing
      with anxiety, no motivation for changing this suffering, and an inability to
      receive a higher level of rehabilitative job training in daycare. These problems
      impeded this patient's reintegration into the community. Therefore, the authors
      employed a five-dimension assessment (physical, emotional, cognitive, social, and
      spiritual) in order to address the two major nursing problems. The period of
      nursing care was from October 21, 2016 to January 10, 2017. The two nursing
      problems addressed included: 1) altered thought processes and 2) ineffective
      coping. The author provided potentially helpful nursing processes based on the
      theory of Rational-Emotive Behavior Therapy in order to help the patient cope
      with symptoms, including being controlled and obsessive-compulsive behaviors.
      Meanwhile, a relaxation technique was applied to reduce the patient's feelings of
      discomfort during the nursing processes. As a result, the patient's coping skills
      to deal with symptoms of being controlled, obsession, and compulsion were
      improved through refutation of irrational beliefs. In addition to showing
      rational emotions and appropriate behavior to handle pressures, the patient was
      also able to apply the relaxation technique to relieve the discomfort from
      anxiety and pain as needed. This case report suggests that nurses may implement
      the irrational beliefs refutation training regimen under Rational-Emotive
      Behavior Therapy for similar cases at the beginning of nursing-patients
      relationships. Furthermore, providing relaxation techniques in the nursing
      process may assist patients to deal with stressful life events. The results of
      this nursing experience are expected to help nursing colleagues apply the above
      theory and skills with schizophrenia patients with obsessive-compulsive symptoms.

PMID- 30276780
TI  - Scoping Review of Clinical Outcomes Related to Advanced Training in Wound Care.
AB  - INTRODUCTION: There are different levels of wound education which exist amongst
      healthcare providers treating wounds. It is unknown if advanced wound training
      can lead to improved clinical outcomes. PURPOSE: To review and summarize existing
      literature focused on the impact of different healthcare professionals with
      advanced wound care training and the associated effect of clinical outcomes.
      MATERIALS AND METHODS: The methods used to conduct this scoping review are based
      on the methodological framework developed by Arksey and O'Malley. An electronic
      search was performed by independent reviewers using Scopus, CINAHL, PubMed,
      Google, and EWMA. Consensus decision-making amongst the reviewers resulted in
      relevant final articles being selected for review. RESULTS: In the literature,
      there is no universally accepted definition for advanced training in wound care.
      Seven of the eight selected articles focused on nurses with a specialization in
      wound healing and their impact on wound healing outcomes. The five main themes
      identified were wound improvement, cost savings, influence on other nurses, wound
      recurrence rate, and advanced education. CONCLUSION: A minimum level of advanced
      training or education would be beneficial to ensure consistency in the provision
      of advanced wound care by professionals practicing wound care.

PMID- 30276781
TI  - Linear Wear Rates of a Highly Cross-Linked Polyethylene Hip Liner.
AB  - INTRODUCTION: To help limit wear, newer polyethylene liners, such as the highly
      cross-linked polyethylene (HXLPE) liners, have been developed. These newer liners
      undergo an alternating irradiation process, resulting in a stronger, longer
      lasting liner. The purpose of this study was to analyze the wear rates of
      patients who underwent THA and received a newer generation HXLPE acetabular
      insert. Specifically, we compared: 1) linear vector wear amount and 2) linear
      vector wear rates in patients as an overall cohort and by gender. We also
      assessed patient satisfaction outcomes comparing preoperative Harris Hip Scores
      (HHS) to seven-week, one-year, and three-year HHS scores. MATERIALS AND METHODS:
      A total of 23 patients who underwent total hip arthroplasty (THA) with direct
      superior approach by a fellowship-trained orthopaedic surgeon at a private
      practice institution were analyzed after receiving institutional review board
      approval. Patients had a minimum two-year follow up, with the mean follow up
      being four years (range, three to five years). All patients received a 36-mm
      ceramic femoral head with an HXLPE liner. 2D radiographic polyethylene wear
      analysis was performed using the Martell Hip Analysis Suite (HAS; University of
      Chicago, Illinois), which has been previously validated in the literature.
      Outcomes were assessed using Harris Hip Scores. RESULTS: A five-year linear wear
      rate of 0.073 mm/year (range, 0 to 0.160 mm/year) and an overall mean linear wear
      rate of 0.096 mm/year (range, 0 to 0.277 mm/year) were found. No significant
      differences in wear were seen between genders. Additionally, patients reported
      significantly better results at seven-weeks (83 points [range, 59 to 100 points])
      and one-year (94 points [range, 85 to 100 points]) than preoperative (52 points
      [range, 34 to 73 points]) HSS scores (p<0.05). No patients underwent revision
      THA. CONCLUSION: The results from this study highlight the benefits of using an
      HXLPE polyethylene liner in THA patients and further validates previously
      reported wear rates of HXLPE liners. After an early "wear in" period during the
      first year, the wear rates steadily decreased over time. This liner showed
      excellent early outcomes as no patients underwent revision THA. Furthermore, even
      as early as seven postoperative weeks, patients reported significantly better HHS
      scores. Future studies should track the same patient cohort over time to help
      develop a wear-rate prediction model.

PMID- 30276782
TI  - A Surgical Case of Inferior Mesenteric Arteriovenous Malformation.
AB  - The treatment option for inferior mesenteric arteriovenous malformations is under
      debate because of the number of cases. We, herein, report about a 35-year-old man
      with congenital inferior mesenteric artery malformation (AVM) presenting with
      mucous stool and severe abdominal pain. The radical operation, after building the
      diverting stoma, minimized the extent of the resection. This is the first
      reported case where surgical management was used to control severe symptoms
      induced by inferior mesenteric AVM.

PMID- 30276783
TI  - Can the General Surgeon Use Quilting Sutures to Prevent Seromas Following
      Abdominal Wall Surgery?
AB  - A common post-operative complication of many operations is seroma formation,
      which, while generally considered to be relatively minor, can be problematic for
      patients and a drain on healthcare resources due to the need for frequent
      outpatient reviews and repeated aspirations. Several mechanisms have been
      implicated in the development of seromas, and drains have traditionally been used
      as a preventative strategy. However, drains are falling out of favour, not least
      because the evidence to support their use is limited and conflicting. In recent
      years, the use of quilting sutures, also known as progressive tension sutures, is
      starting to emerge as a favourable alternative for preventing post-operative
      seroma formation. Several studies and trials support their use in abdominal wall
      operations such as abdominoplasties and at abdominal wall donor sites in
      reconstructive breast operations. General surgeons perform many operations on the
      abdominal wall, such as ventral hernia repair, that predispose the patient to
      seroma formation. Can quilting sutures be used in operations on the abdominal
      wall to prevent seroma formation? This aim of this review was to evaluate the use
      of quilting sutures as described in several studies to reduce the incidence of
      post-operative seroma.

PMID- 30276784
TI  - Pain Reduction with Negative Pressure on Surgical Site Incisions.
AB  - Postoperative pain management for surgery in the lower extremities has
      historically been managed mechanically through the use of elevation, ice,
      compression and drains. Pharmacological management includes the use of nerve
      blocks and analgesics. Due to the current opioid crisis, new methods are being
      sought to reduce post-operative pain so that patients are at lower risk for
      opioid addiction. Postoperative edema control is vital to reduce tension on the
      incision, since increased incisional tension may cause an increase in pain at the
      surgical site. Ice, elevation, compression and drains all contribute to edema
      reduction, and thereby reduce pain and incisional tension. This report introduces
      a new method for post-operative pain control in lower-extremity surgery. In the
      author's present clinical experience with 15 patients, the application of
      negative pressure at the incision site using the PREVENATM Incision Management
      System (KCI USA, Inc., San Antonio, TX) was associated with a decrease in post
      operative pain as well as a decrease in the use of narcotics for post-operative
      pain management.

PMID- 30276785
TI  - Intracorporeal Anastomosis in Both Elective and Emergency Right Hemicolectomy:
      Our Experience.
AB  - PURPOSE: The aim of this study was to examine whether intracorporeal anastomosis
      (IA) after laparoscopic right hemicolectomy (LRH) is a safe procedure in both
      emergency and elective settings. METHODS: A retrospective review of all
      consecutive adult patients (age > 17 years) who underwent LRH from November 2014
      to May 2018 at S. Andrea Hospital, La Spezia, was performed. The primary and
      secondary outcomes were the anastomotic leak rate and the operative time,
      respectively. Both IA and extracorporeal anastomosis (EA) were performed
      according to standardized techniques by the same team of experienced surgeons.
      Our findings were compared to literature data on recent studies comparing IA and
      EA during LRH. RESULTS: During the observation period, 167 patients underwent RH
      at our institution: IA was performed in 115. The mean age was 73.5 y. Thirty
      three RH were performed in an emergency setting: 15 laparotomic procedures, 3
      conversions from laparoscopic to open, 6 laparoscopic-assisted with EA, and 9
      complete IA. The remaining 134 patients underwent elective RH: IA was performed
      in 106. The overall anastomotic leak rate in LHR IA was 2.6% (3/115), and no
      anastomotic leak was reported in the emergency group (0/9). The mean operative
      time was 180 min. In our experience, the operative time is related to the
      surgeon's experience and confidence with the technique, and not to the
      anastomosis technique per se. CONCLUSION: Consistent with the literature data, IA
      in LRH was associated with better outcomes than EA in both elective and emergency
      settings.

PMID- 30276786
TI  - Clinical Results of Direct Anterior Approach THA with Minimal Fluoroscopic
      Exposure Optimization Techniques.
AB  - PURPOSE: To determine if low-level intraoperative fluoroscopy usage is associated
      with increased complications during an initial series for an experienced surgeon
      transitioning to direct anterior approach (DAA) for total hip arthroplasty (THA).
      MATERIALS AND METHODS: Subjects who underwent DAA were eligible for analysis.
      Inclusion criteria included the first 50 subjects who underwent DA hip
      arthroplasty by a single surgeon (January 2013 to December 2014). Total operating
      room (OR) time, fluoroscopy absorbed dose, flouoroscopy time, procedure time, and
      complications were collected and analyzed. Subject demographics were also
      collected with subjects divided by date of surgery to one of two possible groups.
      Simple linear regression analysis was performed to determine the relation between
      case number and both radiation dose and fluoroscopy time. RESULTS: Subjects
      underwent DAA total hip arthroplasty (n=45). Total OR time ranged from 1.1hrs up
      to 2.5 hours. Surgeries required an average fluoroscopic time of 7.8 seconds,
      with improvement over the series of 3.7 seconds. The average radiation dose or
      fluoroscopy was 2.6 mrem per case. This resulted in a total estimated exposure of
      127 mrem over a 23-month period. No patients suffered intraoperative or
      postoperative fractures or revisions. No significant difference was found for the
      groups by weight, age, height, and body mass index. Regression analysis yielded a
      statistically significant (p<0.05) decrease in fluoroscopy time of 0.36 seconds
      per case over the 45 cases studied. CONCLUSION: An experienced single surgeon's
      learning curve in DAA THA can be accelerated, with proper training and technique,
      within a lifetime case experience less than 50 procedures. Surgeons should be
      aware that with proper techniques and sufficiently-experienced teams, a flattened
      learning curve is attainable while minimizing fluoroscopy exposure and
      maintaining clinical outcomes.

PMID- 30276787
TI  - The Value of Somatostatin Receptor Scintigraphy (SRS) in Patients with NETG1/G2
      Pancreatic Neuroendocrine Neoplasms (p-NENs).
AB  - BACKGROUND: Neuroendocrine neoplasms of the pancreas (p-NEN) are common gastro
      entero-pancreatic neuroendocrine neoplasms (GEP-NENs). The aim of this
      retrospective study was to review the of value of Somatostatin Receptor
      Scintigraphy (SRS) in initial detection of p-NEN, evaluation of tumour extent and
      as imaging follow-up after radical surgery in patients with confirmed well
      (NETG1) or moderate (NETG2) differentiated p-NEN based on pathological WHO 2017
      classification. MATERIAL AND METHODS: Overall 281 patients with confirmed p-NEN
      were enrolled. The SRS was performed to evaluation of primary p-NEN, also to
      assess clinical stage of disease, based on current World Health Organization
      (WHO) classification and during clinical follow-up. A total of 829 examinations
      were performed over time in these 281 patients using 99mTc HYNICTOC. Images were
      acquired between 1 - 3 h after i.v. injection of radiotracer. Initially whole
      body WB-SPECT and then WB-SPECT/CT, with standard iterative reconstruction were
      used. RESULTS: There were 159 patients with NETG1 (57%) and 122 subjects with
      NETG2 (43%). The female to male ratio was 1.1:1. In 68 patients (22%) with
      NETG1/G2 eight-seven SRS (10%) were performed to confirm initial diagnosis. SRS
      results were as follow: true positive (TP) = 84 (97%), false negative (FN) = 3
      (3%), no true negative (TN) or false positive (FP) results of SRS examination
      (sensitivity of SRS per patient was 96%). In 198 subjects (66%) SRS was used in
      evaluation and re-evaluation of the clinical stage, A total of 661 (80%)
      examinations were carried out in these patients. There were TP=514 (77%), TN=136
      (21%), FN=7 (1%) and FP=4 (1%) results. The sensitivity and specificity per
      patient were: 96% and 95%. The sensitivity and specificity per study: 98% and
      97%. In 35 patients (12%) SRS was used as imaging follow-up after radical
      surgery, there were overall 81 examination (10%) which were performed. There were
      76 (91%) TN results of examinations of SRS and in 4 patients we identified
      recurrence (TP). In total, which consists of initial diagnosis/staging and follow
      up patients, the sensitivity of SRS was 96% and specificity 97% per patient and
      per study sensitivity and specificity was 98%. CONCLUSIONS: SRS using 99mTc
      HYNICTOC acquired in WB-SPECT or WB-SPECT/CT techniques is an excellent imaging
      modality in detection of primary NETG1/G2 p-NEN. Our study confirms that SRS has
      high sensitivity and specificity, as a result has tremendous value as an
      examination method to assess clinical stage of disease and as an imaging follow
      up after radical treatment.

PMID- 30276788
TI  - Diagnostic difficulties in neuroendocrine tumors - intrapancreatic accessory
      spleen.

PMID- 30276789
TI  - Bioactive lipids and pathological retinal angiogenesis.
AB  - Angiogenesis, disruption of the retinal barrier, leukocyte-adhesion and oedema
      are cardinal signs of proliferative retinopathies that are associated with vision
      loss. Therefore, identifying factors that regulate these vascular dysfunctions is
      critical to target pathological angiogenesis. Given the conflicting role of
      bioactive lipids reported in the current literature, the goal of this review is
      to provide the reader a clear road map of what has been accomplished so far in
      the field with specific focus on the role of polyunsaturated fatty acids (PUFAs)
      derived metabolites in proliferative retinopathies. This necessarily entails a
      description of the different retina cells, blood retina barriers and the role of
      (PUFAs)-derived metabolites in diabetic retinopathy, retinopathy of prematurity
      and age-related macular degeneration as the most common types of proliferative
      retinopathies.

PMID- 30276790
TI  - Ranging behavior and potential for territoriality in equatorial sakis (Pithecia
      aequatorialis) in Amazonian Ecuador.
AB  - OBJECTIVES: Territoriality refers to the consistent defense of an area within the
      home range (HR) against intrusions of conspecifics. It implies exclusive space
      use with low degree of overlap among neighboring groups, high site fidelity,
      specific ranging behavior such as high mobility relative to HR size and frequent
      visits of territory borders, and monitoring behavior. We examined ranging
      behavior and use of space to evaluate territoriality in Pithecia aequatorialis in
      Ecuador. MATERIALS AND METHODS: Between 2005 and 2015, we monitored one main
      study group continuously and five additional groups for shorter periods (5 months
      to 2.5 years) at the Tiputini Biodiversity Station, in eastern Ecuador. We scored
      the location of the study groups at 20 min intervals during, on average, 5 days
      per month. We estimated saki HRs and core areas (CAs) using the fixed kernel
      density method (95 and 50%, respectively). RESULTS: The average HR size was 57 ha
      and the average CA 14 ha. The degree of overlap between HRs of neighboring groups
      was low (2-9%). For the main study group, the average overlap between annual HRs
      was 82%. Mean daily path length across groups was 1,151 m; the defensibility
      index varied between 1.1 and 2.3 (values >1 are suggestive of territoriality),
      and the fractional monitoring rate varied between 0.06 and 0.15 (values >0.08 are
      suggestive of territoriality). Groups did not visit their HR borders (100 m inner
      buffer) more often than would be expected by chance. Travel speed and directness
      were comparable between the borders and the centers of groups' HRs. DISCUSSION:
      Our multiyear study suggests that equatorial sakis show low degree of range
      overlap and high site fidelity and have the potential to be territorial, given
      their high mobility relative to HR size that allows for frequent border
      monitoring. Nevertheless, their movement patterns in border areas did not reveal
      evidence for monitoring behavior.

PMID- 30276792
TI  - Starting with a lower daily dose of dasatinib in patients with chronic myeloid
      leukemia in chronic phase: Less is more, or is it?

PMID- 30276791
TI  - Contrasting characteristics of daily physical activity in older adults by cancer
      history.
AB  - BACKGROUND: Using objectively collected physical activity (PA) data from the
      Baltimore Longitudinal Study of Aging, the authors tested whether patterns of
      daily activity and sedentary time differed by cancer survivorship in older
      adults. METHODS: In total, 659 participants (mean age +/- standard deviation, 71
      +/- 10 years; 51% women) who had self-reported information on cancer history were
      instructed to wear an accelerometer for 7 consecutive days. Accelerometer data
      were summarized into: 1) PA volume and 2) activity fragmentation (interrupted
      activity), expressed as both continuous and as dichotomized (low and high)
      variables. Participants were categorized into 4 groups by cross-classification of
      dichotomous PA volume and fragmentation. Multiple regression models were used to
      estimate differences in PA patterns by cancer history. RESULTS: Cancer survivors
      averaged 0.12 fewer log-transformed activity counts per day (standard error,
      0.05; P = .02) than individuals who reported no history of cancer after adjusting
      for demographics, behavioral factors, and comorbidities. Although fragmentation
      did not differ by cancer survivorship in the continuous model (P = .13), cancer
      survivorship was associated with 77% greater odds (odds ratio, 1.77; 95%
      confidence interval, 1.11-2.82) of having high (vs low) fragmentation and 94%
      greater odds (odds ratio, 1.94; 95% confidence interval, 1.13-3.33) of having
      combined low PA/high fragmentation (vs high PA/low fragmentation) relative to
      those with no cancer history. CONCLUSIONS: The current findings suggest that
      cancer survivors engage in lower total daily PA and that they perform this
      activity in a more fragmented manner compared with adults without a history of
      cancer. These results may reflect the onset and progression of a low-activity
      phenotype that is more vulnerable to heightened levels of fatigue and functional
      decline with aging.

PMID- 30276793
TI  - Impact of change in head and neck position on ultrasound localisation of the
      cricothyroid membrane: an observational study.
AB  - The ideal position for performing surgical cricothyroidotomy is with full neck
      extension. Some authors have recommended marking the cricothyroid membrane before
      general anaesthesia, typically with the patient's head and neck in a neutral
      position. The primary aim of this observational study was to determine whether
      skin marks made over the centre of the cricothyroid membrane with the head and
      neck in the neutral position moved outside the boundaries of the membrane when
      the neck was subsequently extended. The secondary aim was to assess changes in
      the height of the cricothyroid membrane between the neutral and extended
      positions. Twenty-two volunteers completed the study. With the head and neck in
      the neutral position, the distance between the upper and lower borders ('height')
      of the cricothyroid membrane was measured by a radiologist using ultrasound. The
      skin was marked over the mid-point of the membrane. The subject then maximally
      extended the neck, and the measurements and marking were repeated. The skin
      marking over the centre point of the cricothyroid membrane moved by median (IQR
      [range]) 5 (4-6 [0-10]) mm when the head and neck were moved from a neutral to a
      fully extended position. The initial skin mark moved to lie outside the boundary
      of the cricothyroid membrane in 12 of 22 subjects after extending the neck. The
      height of the cricothyroid membrane increased by 30% with the neck extended. We
      recommend that marking the skin in preparation for cricothyroidotomy should be
      performed with the neck extended, not with the head and neck in the neutral
      position as previously suggested.

PMID- 30276794
TI  - Direct oral anticoagulants: peri-operative considerations and controversies.

PMID- 30276795
TI  - Identifying fossil Myrtaceae leaves: the first described fossils of Syzygium from
      Australia.
AB  - PREMISE OF THE STUDY: Although leaves of Myrtaceae are easily identified to
      family level, very few studies have convincingly identified fossil Myrtaceae
      leaves to living genera. We used a broadly comparative approach with a large data
      set of extant taxa to confidently assign the mummified remains of myrtaceous
      leaves from early Miocene sediments at Kiandra (New South Wales, Australia) to a
      living genus. METHODS: Fossils were identified using a nearest living relative
      approach, against a database of 232 extant broadleaf rainforest species of
      Myrtaceae. Leaf cuticles were prepared from 106 species, sourced from herbarium
      specimens as well as some living individuals, and a further 127 records were
      assembled from the literature. A set of simple but phylogenetically informative
      cuticular characters were observed, described, and recorded under both scanning
      electron microscopy and standard light microscopy. KEY RESULTS: A new fossil
      species of Syzygium Gaertn. is described from mummified remains found in early
      Miocene (21.5-21.7 Ma) sediments. The fossil taxon is here named Syzygium
      christophelii sp. nov., in honor of the late Australian paleobotanist David
      Christophel. CONCLUSIONS: These fossils represent some of the most confidently
      described Myrtaceae leaf fossils published to date and are the first and oldest
      described fossil record of Syzygium from Australia. While several fossil parataxa
      have been illustrated from New Zealand, and several fossil species of Syzygium
      have previously been proposed in the literature, many of these fossils lack
      characters for a confident diagnosis.

PMID- 30276796
TI  - Editorial: Aboriginal, Torres Strait Islander and Maori Women.

PMID- 30276797
TI  - Reply to Starting with a lower daily dose of dasatinib in patients with chronic
      myeloid leukemia in chronic phase: Less is more, or is it?

PMID- 30276798
TI  - Renal cell carcinoma and pathologic nodal disease: Implications for American
      Joint Committee on Cancer staging.
AB  - BACKGROUND: Lymph node (LN) metastases are associated with poor outcomes for
      patients with renal cell carcinoma (RCC). This study compared the survival
      outcomes of patients with stage III, node-positive disease (pT123 N1 M0 ) and
      patients with stage III, node-negative disease (pT3 N0 M0 ). METHODS: A database
      of 4652 patients with RCC of any histological subtype treated with surgery at The
      University of Texas MD Anderson Cancer Center from 1993 to 2012 was
      retrospectively assessed. A total of 115 patients with pT123 N1 M0 disease, 274
      patients with pT3 N0 M0 disease, and 523 patients with pT123 N0/x M1 disease were
      included. Overall survival (OS) and cancer-specific survival (CSS) were estimated
      and compared between each cohort. RESULTS: Median OS and CSS times were
      significantly better for pT3 N0 M0 patients than pT123 N1 M0 patients (OS, 10.2
      vs 2.4 years, P < .0001; CSS, not reached vs 2.8 years, P < .0001). Similar
      median OS and CSS times were noted for pT123 N1 M0 and pT123 N0/x M1 patients
      (OS, 2.4 vs 2.4 years; P = .62; CSS, 2.8 vs 2.4 years; P = .10). In a
      multivariate analysis, tumor grade (hazard ratio [HR] for OS, 2.47; P < .0001; HR
      for CSS, 2.99; P < .0001) and pathologic LN involvement (HR for OS, 2.44; P <
      .0001; HR for CSS, 2.85; P < .0001) were associated with worse OS and CSS.
      CONCLUSIONS: Among RCC patients classified with stage III disease, those with
      pT123 N1 M0 disease had significantly worse survival than those with pT3 N0 M0
      disease. OS and CSS were similar for patients with pT123 N1 M0 disease and
      patients with pT123 N0/x M1 disease (stage IV). If validated, these findings
      suggest that RCC patients with nodal disease should be reclassified as having
      stage IV disease.

PMID- 30276799
TI  - Improving postpartum screening after diabetes in pregnancy: Results of a pilot
      study in remote Australia.
AB  - BACKGROUND: The postpartum period is a critical time to improve health outcomes
      for Aboriginal women, particularly for those who have chronic conditions. AIMS:
      To assess enhanced support methods (for women following diabetes in pregnancy
      (DIP)) to improve completion rates of recommended postpartum health checks.
      MATERIALS AND METHODS: Fifty-three Aboriginal women in the Northern Territory
      (NT) were contacted in the postpartum period to encourage medical check-ups.
      Messages were delivered through phone (call or text messages) or other methods
      (Facebook or email). The primary outcome was postpartum blood glucose testing
      (oral glucose tolerance testing (OGTT), random or fasting glucose and HbA1c).
      RESULTS: Establishing contact with women was difficult. Of 137 messages sent to
      52 women, 22 responded (42%). Phone was the most common contact method with
      successful contact made from 16 of 119 (13%) attempts. Rates of postpartum OGTT
      completion were higher in the group successfully contacted (32% vs 7%). However,
      for any postpartum glucose testing (including OGTT and HbA1c) rates were 25 of 42
      (60%) and neither success in making contact nor the contact method was associated
      with higher rates. CONCLUSIONS: The small sample size limits our conclusions;
      however, results highlight that engaging remote women postpartum is difficult.
      While rates of postpartum OGTT completion differed according to successful
      contacts, rates of any postpartum blood glucose testing did not. Further research
      is needed to explore feasible intervention methods to improve postpartum
      screening after a pregnancy complicated by diabetes.

PMID- 30276800
TI  - Parental distress and desire for information regarding long-term implications of
      pediatric cancer treatment.
AB  - BACKGROUND: Parents of children with cancer have unmet information needs
      regarding future limitations resulting from cancer or its treatment. Prior
      research has demonstrated that, in early care discussions, clinicians focus on
      the acute effects of therapy rather than long-term limitations, partly due to
      worries of causing distress. The validity of concerns regarding distress is
      unknown. In the current study, the authors evaluated parental distress associated
      with information regarding future limitations, and the extent to which distress
      is associated with information preferences. METHODS: The authors surveyed 355
      parents of children with cancer within 3 months of diagnosis, and the children's
      physicians at Dana-Farber Cancer Institute/Boston Children's Cancer and Blood
      Disorders Center and the Children's Hospital of Philadelphia. The primary outcome
      was parental distress associated with information regarding long-term
      limitations. RESULTS: Approximately 46% of parents found information regarding
      future limitations to be extremely or very upsetting. In multivariate analysis,
      parents were more likely to consider information regarding future limitations
      distressing if they also found prognostic information upsetting (odds ratio [OR],
      5.36; P<.001), struggled to accept their child's illness (OR, 2.57; P<.001), or
      had depression (OR, 1.79; P=.01). However, approximately 92% of parents
      considered information regarding potential future limitations to be
      extremely/very important. Those who found information regarding future
      limitations distressing were more likely to consider it important (96% vs 89%;
      P=.03) and to desire a precise understanding of their child's risks (92% vs 80%;
      P=.001). CONCLUSIONS: Although information regarding future limitations caused by
      cancer treatment is upsetting to many parents, the majority of them desire this
      information, and those who are distressed are more likely to value this
      information.

PMID- 30276801
TI  - A novel heterozygous variant p.(Trp538Arg) of SYNM is identified by whole-exome
      sequencing in a Chinese family with dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is a relatively frequent myocardial disease that may
      lead to heart failure, syncope, and sudden cardiac death. Genetic factors play
      important roles in the etiology of the disease. To date, at least 50 genes have
      been identified in patients with DCM, among them, only three mutations have been
      reported in Synemin (SYNM) gene. In this study, we investigate a Chinese family
      of three generations with four patients with DCM. Employing whole-exome
      sequencing (WES) and bioinformatics strategies, a novel heterozygous missense
      mutation p.(Trp538Arg) of SYNM was identified and cosegregated with the affected
      family members. The missense mutation locates in the C-terminal domain of SYNM
      and leads to a substitution of tryptophan by arginine and may cause the structure
      change of synemin protein. In conclusion, we employed WES to detect the mutations
      of DCM patients and identified a novel likely pathogenic mutation in SYNM gene.
      Our study not only expands the spectrum of SYNM mutations, it further confirms
      that mutations in SYMN may underlie nonfamilial DCM, and offers genetic testing
      information to additional DCM patients.

PMID- 30276803
TI  - Characterization of the mating system of a native perennial tetraploid herb,
      Silene stellata.
AB  - PREMISE OF THE STUDY: Nursery pollination systems can range from obligate to
      facultative. In a system where generalists provide substantial pollination
      service, an important question is whether the cost of seed predation outweighs
      the benefit provided by the nursery pollinator to cause the plant to evolve
      toward more generalized pollination. Using a facultative system native to North
      America, we tested whether nursery pollinator vs. strictly mutualistic
      generalists affect mating-system parameters of the host plant and explored the
      implications for long-term coevolution. METHODS: We used paternity analyses with
      11 microsatellite markers to characterize the mating system of Silene stellata
      when pollination service is primarily through the nursery pollinator Hadena
      ectypa and generalist moths. KEY RESULTS: Our experimental population of S.
      stellata was predominantly outcrossing (average outcrossing rate t = 0.83), and
      mating-system parameters were similar between pollinator groups. We detected
      significant correlations in both selfing and outcrossed paternity at the fruit
      and maternal family level, corresponding to limited pollen dispersal (mean = 3.9
      m). Among individuals, variation in anther-stigma separation was positively
      associated with outcrossing rate, which suggests the importance of herkogamy in
      preventing selfing. CONCLUSIONS: Correlated paternity suggests that seeds from
      the same fruit and/or plants are sired by a limited number of pollen donors,
      resulting from low pollen dispersal and potential male-male competition. The
      similar mating-system parameters of the two pollinator groups suggest that
      selection for higher outcrossing in S. stellata is likely to be through floral
      design rather than through increased pollinator specialization with H. ectypa.

PMID- 30276804
TI  - Real-world database examining the association between hydroxychloroquine and
      retinopathy in Taiwan.

PMID- 30276802
TI  - Nociceptin/Orphanin FQ (N/OFQ) conjugated to ATTO594: a novel fluorescent probe
      for the N/OFQ (NOP) receptor.
AB  - BACKGROUND AND PURPOSE: The nociceptin/orphanin FQ (N/OFQ) receptor (NOP) is a
      member of the opioid receptor family and is involved in a number of physiological
      responses, pain and immune regulation as examples. In this study, we conjugated a
      red fluorophore-ATTO594 to the peptide ligand N/OFQ (N/OFQATTO594 ) for the NOP
      receptor and explored NOP receptor function at high (in recombinant systems) and
      low (on immune cells) expression. EXPERIMENTAL APPROACH: We assessed N/OFQATTO594
      receptor binding, selectivity and functional activity in recombinant (CHO) cell
      lines. Live cell N/OFQATTO594 binding was measured in (i) HEK cells expressing
      NOP and NOPGFP receptors, (ii) CHO cells expressing the hNOPGalphaqi5 chimera (to
      force coupling to measurable Ca2+ responses) and (iii) freshly isolated human
      polymorphonuclear cells (PMN). KEY RESULTS: N/OFQATTO594 bound to NOP receptor
      with nM affinity and high selectivity. N/OFQATTO594 activated NOP receptor by
      reducing cAMP formation and increasing Ca2+ levels in CHOhNOPGalphaqi5 cells.
      N/OFQATTO594 was also able to visualize NOP receptors at low expression levels on
      PMN cells. In NOP-GFP-tagged receptors, N/OFQATTO594 was used in a FRET protocol
      where GFP emission activated ATTO, visualizing ligand-receptor interaction. When
      the NOPGFP receptor is activated by N/OFQATTO594 , movement of ligand and
      receptor from the cell surface to the cytosol can be measured. CONCLUSIONS AND
      IMPLICATIONS: In the absence of validated NOP receptor antibodies and issues
      surrounding the use of radiolabels (especially in low expression systems), these
      data indicate the utility of N/OFQATTO594 to study a wide range of N/OFQ-driven
      cellular responses.

PMID- 30276805
TI  - SOX-11 regulates LINE-1 retrotransposon activity during neuronal differentiation.
AB  - Activity of the human long interspersed nuclear elements-1 (LINE-1)
      retrotransposon occurs mainly in early embryonic development and during
      hippocampal neurogenesis. SOX-11, a transcription factor relevant to neuronal
      development, has unknown functions in the control of LINE-1 retrotransposon
      activity during neuronal differentiation. To study the dependence of LINE-1
      activity on SOX-11 during neuronal differentiation, we induced differentiation of
      human SH-SY5Y neuroblastoma cells and adult adipose mesenchymal stem cells
      (hASCs) to a neuronal fate and found increased LINE-1 activity. We also show that
      SOX-11 protein binding to the LINE-1 promoter is higher in differentiating
      neuroblastoma cells, while knock-down of SOX-11 inhibits the induction of LINE-1
      transcription in differentiating conditions. These results suggest that
      activation of LINE-1 retrotransposition during neuronal differentiation is
      mediated by SOX-11.

PMID- 30276806
TI  - Reliability and predictive validity of the Standardized Infant NeuroDevelopmental
      Assessment neurological scale.
AB  - AIM: To assess reliability and predictive validity of the neurological scale of
      the Standardized Infant NeuroDevelopmental Assessment (SINDA), a recently
      developed assessment for infants aged 6 weeks to 12 months. METHOD: To assess
      reliability, three assessors independently rated video-recorded neurological
      assessments of 24 infants twice. Item difficulty and discrimination were
      determined. To evaluate predictive validity, 181 infants (median gestational age
      30wks [range 22-41wks]; 92 males, 89 females) attending a non-academic outpatient
      clinic were assessed with SINDA's neurological scale (28 dichotomized items).
      Atypical neurodevelopmental outcome at 24 months or older corrected age implied a
      Bayley Mental Developmental Index or Psychomotor Developmental Index lower than
      70 or a diagnosis of cerebral palsy (CP). Predictive values were calculated from
      SINDA (2-12mo corrected age, median 3mo) and typical versus atypical outcome.
      RESULTS: Intraclass correlation coefficients of intrarater and interrater
      agreement of the neurological score varied between 0.923 and 0.965. Item
      difficulty and discrimination were satisfactory. At 24 months or older, 56
      children (31%) had an atypical outcome (29 had CP). Atypical neurological scores
      (below 25th centile, <=21) predicted atypical outcome and CP with sensitivities
      of 89% and 100%, and specificities of 94% and 81% respectively. INTERPRETATION:
      SINDA's neurological scale is reliable and in a non-academic outpatient setting
      has a satisfactory predictive validity for atypical developmental outcome,
      including CP, at 24 months or older. WHAT THIS PAPER ADDS: The Standardized
      Infant NeuroDevelopmental Assessment's neurological scale has a good to excellent
      reliability. The scale has promising predictive validity for cerebral palsy. The
      scale has promising predictive validity for other types of atypical developmental
      outcome.

PMID- 30276807
TI  - Epigenetic Cues Modulating the Generation of Cell-Type Diversity in the Cerebral
      Cortex.
AB  - The cerebral cortex is composed of a large variety of distinct cell-types
      including projection neurons, interneurons and glial cells which emerge from
      distinct neural stem cell (NSC) lineages. The vast majority of cortical
      projection neurons and certain classes of glial cells are generated by radial
      glial progenitor cells (RGPs) in a highly orchestrated manner. Recent studies
      employing single cell analysis and clonal lineage tracing suggest that NSC and
      RGP lineage progression are regulated in a profound deterministic manner. In this
      review we focus on recent advances based mainly on correlative phenotypic data
      emerging from functional genetic studies in mice. We establish hypotheses to test
      in future research and outline a conceptual framework how epigenetic cues
      modulate the generation of cell-type diversity during cortical development. This
      article is protected by copyright. All rights reserved.

PMID- 30276808
TI  - Identification and pharmacological profile of SPP1, a potent, functionally
      selective and brain penetrant agonist at muscarinic M1 receptors.
AB  - BACKGROUND AND PURPOSE: We aimed to identify and develop novel, selective
      muscarinic M1 receptor agonists as potential therapeutic agents for the
      symptomatic treatment of Alzheimer's disease. EXPERIMENTAL APPROACH: We developed
      and utilized a novel M1 receptor occupancy assay to drive a structure activity
      relationship in a relevant brain region while simultaneously tracking drug levels
      in plasma and brain to optimize for central penetration. Functional activity was
      tracked in relevant native in vitro assays allowing translational (rat-human)
      benchmarking of structure-activity relationship molecules to clinical
      comparators. KEY RESULTS: Using this paradigm, we identified a series of M1
      receptor selective molecules displaying desirable in vitro and in vivo properties
      and optimized key features, such as central penetration while maintaining
      selectivity and a partial agonist profile. From these compounds, we selected
      spiropiperidine 1 (SPP1). In vitro, SPP1 is a potent, partial agonist of cortical
      and hippocampal M1 receptors with activity conserved across species. SPP1
      displays high functional selectivity for M1 receptors over native M2 and M3
      receptor anti-targets and over a panel of other targets. Assessment of central
      target engagement by receptor occupancy reveals SPP1 significantly and dose
      dependently occupies rodent cortical M1 receptors. CONCLUSIONS AND IMPLICATIONS:
      We report the discovery of SPP1, a novel, functionally selective, brain penetrant
      partial orthosteric agonist at M1 receptors, identified by a novel receptor
      occupancy assay. SPP1 is amenable to in vitro and in vivo study and provides a
      valuable research tool to further probe the role of M1 receptors in physiology
      and disease.

PMID- 30276809
TI  - The Case for Mobility Assessment in Hospitalized Older Adults: American
      Geriatrics Society White Paper Executive Summary.
AB  - Mobility can be defined as the ability to move or be moved freely and easily. In
      older adults, mobility impairments are common and associated with risk for
      additional loss of function. Mobility loss is particularly common in these
      individuals during acute illness and hospitalization, and it is associated with
      poor outcomes, including loss of muscle mass and strength, long hospital stays,
      falls, declines in activities of daily living, decline in community mobility and
      social participation, and nursing home placement. Thus, mobility loss can have a
      large effect on an older adult's health, independence, and quality of life.
      Nevertheless, despite its importance, loss of mobility is not a widely recognized
      outcome of hospital care, and few hospitals routinely assess mobility and
      intervene to improve mobility during hospital stays. The Quality and Performance
      Measurement Committee of the American Geriatrics Society has developed a white
      paper supporting greater focus on mobility as an outcome for hospitalized older
      adults. The executive summary presented here focuses on assessing and preventing
      mobility loss in older adults in the hospital and summarizes the recommendations
      from that white paper. The full version of the white paper is available as Text
      S1.

PMID- 30276810
TI  - Behavioural interventions to treat drooling in children with neurodisability: a
      systematic review.
AB  - AIM: To review the evidence for behavioural interventions to reduce drooling in
      children with neurodisability. METHOD: A detailed search in eight databases
      sought studies that: (1) included participants aged 0 to 18 years with
      neurodisability and drooling; (2) provided behavioural interventions targeting
      drooling or a drooling-related behaviour; and (3) used experimental designs. Two
      reviewers extracted data from full-text papers independently. Results were
      tabulated for comparison. The Risk of Bias assessment in N-of-1 Trials scale for
      single case experimental designs (SCEDs) and the Cochrane risk of bias assessment
      tool for randomized controlled trials (RCTs) were applied. RESULTS: Of an initial
      yield of 763, seven SCEDs and one RCT were included. Behavioural interventions
      included the use of reinforcement, prompting, self-management, instruction,
      extinction, overcorrection, and fading. Each assessed body functions or
      structures' outcomes (drooling frequency and severity); three included activity
      outcomes (mouth drying, head control, eye contact, and vocalizations) and none
      assessed participation or quality of life. While each study reported positive
      effects of intervention, risk of bias was high. INTERPRETATION: Low-level
      evidence suggests behavioural interventions may be useful for treatment of
      drooling in children with neurodisability. Well-designed intervention studies are
      urgently needed to determine effectiveness. WHAT THIS PAPER ADDS: Behavioural
      interventions used to treat drooling included reinforcement, prompting, self
      management, extinction, overcorrection, instruction, and fading. Interventions
      targeted body structures and function-level outcomes and activity-level outcomes.
      Low-level evidence supports the use of behavioural intervention to treat
      drooling.

PMID- 30276811
TI  - Structural and functional neuroimaging in attention-deficit/hyperactivity
      disorder.
AB  - Over the last decade, there has been a dramatic increase in the number of
      neuroimaging studies in attention-deficit/hyperactivity disorder (ADHD). In terms
      of brain structure, magnetic resonance imaging (MRI), and diffusion tensor
      imaging studies have evidenced differences in volume, surface-based measures
      (cortical thickness, surface area, and gyrification), and white matter integrity
      in different cerebral regions, in children and adults with ADHD compared to
      population norms. Abnormalities in the basal ganglia, prefrontal structures, and
      the corpus callosum have been the most consistently reported findings across
      studies. Hemodynamic (functional MRI, functional near-infrared spectroscopy,
      positron emission tomography, single-photon emission computed tomography) and
      magnetoencephalography measurements have also shown differences in neural
      activity during the execution of neuropsychological tasks and during rest, in
      widespread regions of the brain. Importantly, multimodal studies combining
      structural and functional methods have shown an intercorrelation between
      structural and functional abnormalities in ADHD. Further longitudinal studies are
      needed to clarify the effects of age and medication on brain structure and
      function in individuals with ADHD. WHAT THIS PAPER ADDS: In attention
      deficit/hyperactivity disorder (ADHD), the brain is characterized by abnormal
      neural network interplay. Structural and functional cerebral abnormalities in
      ADHD are intercorrelated. Currently there is no neural biomarker that can be used
      in diagnosis. Longitudinal studies have shed light on the brain correlates of
      ADHD over the lifespan. The effects of stimulant intake on the brain correlates
      of ADHD remain unclear.

PMID- 30276812
TI  - Developmental trajectories of adaptive functioning following early mild traumatic
      brain injury.
AB  - Adaptive behavior impairments have been reported in children with severe
      traumatic brain injury (TBI) but are not typically found following mild TBI. It
      is possible that mild TBI induces subtle changes in adaptive functioning that are
      not captured in conventional group comparisons. This study aimed to explore time
      course changes in adaptive functioning following early mild TBI. Parents of 63
      children with mild TBI and 53 children with orthopedic injuries aged between 1.5
      and 5 years at the time of injury completed the Adaptive Behavior Assessment
      System-II at three time points: retrospectively to assess pre-injury functioning,
      then at 6 and 18 months post-injury. Developmental trajectories of adaptive
      functioning domains (practical, conceptual, and social) reported by parents were
      modeled using linear mixed-model analyses. Findings suggest that mild TBI may
      disrupt the expected developmental progression of children's social adaptive
      behavior, but does not appear to alter practical and conceptual domains.

PMID- 30276813
TI  - The underappreciated extent of cannibalism and ophiophagy in African cobras.

PMID- 30276814
TI  - Pit viper envenomation in a barn cat.

PMID- 30276816
TI  - Iatrogenic subcutaneous facial emphysema secondary to a Class V dental
      restoration: a case report.
AB  - Subcutaneous facial emphysema (SFE) following routine dental operative procedure
      is an uncommon but potentially life-threatening complication. The present case
      details a Class V restoration where air was introduced into the fascial tissue
      planes via the gingival sulcus from the use of an air-driven dental handpiece.
      Although the SFE is usually self-limiting within 3-10 days, such instances should
      be regarded as a medical emergency as in severe cases, the air may spread to the
      neck, mediastinum and thorax to result in cervicofacial emphysema with potential
      pneumomediastinum and pneumothorax.

PMID- 30276815
TI  - Brain correlates of stress-induced peripheral vasoconstriction in patients with
      cardiovascular disease.
AB  - The influence of acute psychological stress on cardiovascular disease is an
      emerging public health concern. Identification of brain mechanisms underlying
      this may aid in the discovery of possible treatments. Acute psychological stress
      may induce arteriolar vasoconstriction and reduce blood flow to vital organs. We
      hypothesized that functional changes in brain regions involved with memory and
      autonomic/emotional regulation are implicated in the vasoconstrictive stress
      response, including the medial prefrontal cortex (anterior cingulate), insula,
      and dorsolateral prefrontal cortex. Subjects with a history of coronary artery
      disease (N = 59) underwent measurement of microvascular vasomotor tone with the
      EndoPAT device and O-15 positron emission tomography (PET) imaging of the brain
      during exposure to mental stress and control conditions. The peripheral arterial
      tonometry (PAT) ratio was calculated as the mean peripheral vasomotor tone during
      stress divided by the mean tone during rest. Whole brain contrasts were performed
      between groups above and below the median PAT ratio, and significant contrasts
      were defined with cutoff p < 0.005. Stress-induced peripheral vasoconstriction
      (below median PAT ratio) was associated with increased stress activation in
      insula and parietal cortex, and decreased activation in the medial prefrontal
      cortex with stress tasks compared to control tasks. These findings demonstrate
      that stress-induced vasoreactivity is associated with changes in brain responses
      to stress in areas involved in emotion and autonomic regulation. These findings
      have important implications on possible treatments for mental stress-induced
      vascular toxicity.

PMID- 30276817
TI  - Ocean warming and copper pollution: implications for metabolic compounds of the
      agarophyte Gelidium floridanum (Gelidiales, Rhodophyta)1.
AB  - Ocean warming is increasing and scientific predictions suggest a rise of up to 4
      degrees C in sea water temperatures. The combination of a polluted and warmer
      environment may be detrimental for aquatic species, especially for primary
      producers such as seaweeds. This study investigated the potential for interactive
      effects of an increased seawater temperature in a copper-rich environment on the
      photosynthetic pigments and metabolic compounds of the red seaweed Gelidium
      floridanum. Seaweed samples were cultivated in a factorial design with
      temperature (24 degrees C and 30 degrees C), copper (0 and 3 MUM), and time (7
      and 14 d). The exposure of G. floridanum to copper and 30 degrees C for 7 d
      resulted in a lower concentration of chlorophyll a, smaller phycobiliprotein rods
      and lower concentration of soluble sugars. After 14 d of cultivation, a higher
      concentration of chlorophyll a and soluble sugars could be observed on seaweeds
      cultivated under 30 degrees C. The accumulation of carotenoids and the release of
      phenolic compounds indicated specific protective mechanisms against temperature
      and copper, respectively. Overall, seaweeds grew less when exposed to copper 3
      MUM at 30 degrees C.

PMID- 30276818
TI  - Endophyte traits relevant to stress tolerance, resource use and habitat of origin
      predict effects on host plants.
AB  - All terrestrial plants are colonized by foliar endophytic fungi that can affect
      plant growth and physiology, but the prediction of these effects on the plant
      host remains a challenge. Here, we examined three paradigms that potentially
      control how endophytes affect plant hosts: habitat adaptation, evolutionary
      history and functional traits. We screened 35 plant-endophyte pairings in a
      microcosm experiment under well-watered and drought conditions with Panicum
      virgatum as the host. We related the measured plant responses to fungal
      phylogenetic relatedness, characteristics of fungal habitats across a rainfall
      gradient and functional traits of the fungi related to stress tolerance and
      resource use. The functional traits and habitat characteristics of the fungi
      predicted 26-53% of endophyte-mediated effects on measures of plant growth,
      physiology and survival. Overall, survival was higher for plants grown with more
      stress-tolerant fungi, and aboveground biomass was enhanced by fungi from warmer
      and drier habitats. Plant growth and physiology were also dependent on fungal
      resource use indicators; however, specific predictors were dependent on water
      availability. Simple ecological traits of foliar endophytic fungi observed in
      culture can translate to symbiotic lifestyles. These findings offer new insights
      and key testable predictions for likely pathways by which endophytes benefit the
      plant host.

PMID- 30276819
TI  - An initial investigation of hyperpolarized gas tagging magnetic resonance imaging
      in evaluating deformable image registration-based lung ventilation.
AB  - BACKGROUND: Deformable image registration (DIR)-based lung ventilation mapping is
      attractive due to its simplicity, and also challenging due to its susceptibility
      to errors and uncertainties. In this study, we explored the use of 3D
      Hyperpolarized (HP) gas tagging MRI to evaluate DIR-based lung ventilation.
      METHOD AND MATERIAL: Three healthy volunteers included in this study underwent
      both 3D HP gas tagging MRI (t-MRI) and 3D proton MRI (p-MRI) using balanced
      steady-state free precession pulse sequence at end of inhalation and end of
      exhalation. We first obtained the reference displacement vector fields (DVFs)
      from the t-MRIs by tracking the motion of each tagging grid between the
      exhalation and the inhalation phases. Then, we determined DIR-based DVFs from the
      p-MRIs by registering the images at the two phases with two commercial DIR
      algorithms. Lung ventilations were calculated from both the reference DVFs and
      the DIR-based DVFs using the Jacobian method and then compared using cross
      correlation and mutual information. RESULTS: The DIR-based lung ventilations
      calculated using p-MRI varied considerably from the reference lung ventilations
      based on t-MRI among all three subjects. The lung ventilations generated using
      Velocity AI were preferable for the better spatial homogeneity and accuracy
      compared to the ones using MIM, with higher average cross correlation (0.328 vs
      0.262) and larger average mutual information (0.528 vs 0.323). CONCLUSION: We
      demonstrated that different DIR algorithms resulted in different lung ventilation
      maps due to underlining differences in the DVFs. HP gas tagging MRI provides a
      unique platform for evaluating DIR-based lung ventilation.

PMID- 30276820
TI  - Recovery in the first six months after hand and upper limb burns: A prospective
      cohort study.
AB  - BACKGROUND/AIM: Hands are commonly involved in burn trauma. Occupational therapy
      in the acute phase aims to reduce the risk of deformities and facilitate return
      to usual occupations. This study aimed to describe usual occupational therapy
      care at a major adult burns service, and measure recovery from hand burns in the
      first six months post-acute hospital discharge. METHOD: To describe usual
      occupational therapy care, an audit of patient contact statistics over six months
      was undertaken, and occupational therapy staff were interviewed. To measure
      recovery, a prospective cohort study recruited adults hospitalised with
      hand/upper limb burns at the Victorian Adult Burns Service. Recruitment occurred
      over a four month period. Functional recovery was measured at three time points:
      discharge, three and six months post-discharge. Instruments included the Quick
      Disabilities of the Arm, Shoulder and Hand and the Functional Assessment for
      Burns. RESULTS: Usual care was calculated to be one 30 minute session of daily
      occupational therapy. Interventions were described using the Template for
      Intervention Description and Replication. Participants (N = 10) were aged 22-65
      years and were treated for burns ranging from 2% to 40% total body surface area.
      Scores on the Functional Assessment for Burns suggested high functional
      independence at discharge. Quick Disabilities of the Arm, Shoulder and Hand
      scores improved significantly at each time point, with most substantial
      improvement occurring between discharge and three months. Involvement of the
      first web-space was associated with poorer recovery in the first three months
      post-discharge (P = 0.04). Six participants (60%) had returned to work at the
      three month follow-up, and seven (70%) at six months. CONCLUSION: The Quick
      Disabilities of the Arm, Shoulder and Hand was responsive to recovery in the post
      discharge period. Further research into upper limb recovery following burns is
      needed, including exploration of the relationship between recovery and first web
      space hand burns.

PMID- 30276821
TI  - Corner's rules as a framework for plant morphology, architecture and functioning 
      issues and steps forward.

PMID- 30276822
TI  - Anemia in hospitalized patients: an overlooked risk in medical care.
AB  - BACKGROUND: This study investigated the association between nadir anemia and
      mortality and length of stay (LOS) in a general population of hospitalized
      patients. STUDY DESIGN AND METHODS: A retrospective cohort study of tertiary
      hospital admissions in Western Australia between July 2010 and June 2015. Outcome
      measures were in-hospital mortality and LOS. RESULTS: Of 80,765 inpatients,
      45,675 (56.55%) had anemia during admission. Mild and moderate/severe anemia were
      independently associated with increased in-hospital mortality (odds ratio [OR]
      1.5, 95% confidence interval [CI] 1.36-1.86, p = 0.001; OR 2.77, 95% CI 2.32
      3.30, p < 0.001, respectively). Anemia was also associated with increased LOS,
      demonstrating a larger effect in emergency (mild anemia-incident rate ratio [IRR]
      1.52, 95% CI 1.48-1.56, p < 0.001; moderate/severe anemia-IRR 2.18, 95% CI 2.11
      2.26, p < 0.001) compared to elective admissions (mild anemia-IRR 1.30, 95% CI
      1.21-1.41, p < 0.001; moderate/severe anemia-IRR 1.69, 95% CI 1.55-1.83, p <
      0.001). LOS was longer in patients who developed anemia during admission compared
      to those who had anemia on admission (IRR 1.13, 95% CI 1.10-1.17, p < 0.001). Red
      cell transfusion was independently associated with 2.23 times higher odds of in
      hospital mortality (95% CI 1.89-2.64, p < 0.001) and 1.31 times longer LOS (95%
      CI 1.25-1.37, p < 0.001). CONCLUSION: More than one-third of patients not anemic
      on admission developed anemia during admission. Even mild anemia is independently
      associated with increased mortality and LOS; however, transfusion to treat anemia
      is an independent and additive risk factor.

PMID- 30276823
TI  - Involvement of neutrophils in Chagas disease pathology.
AB  - Chagas disease (CD) is a public health problem in Latin America. The acute phase
      presents nonspecific symptoms and most patients recover from acute parasitemia
      and undergo a prolonged asymptomatic phase. Several years later, about 30% of
      infected individuals develop chronic cardiopathy with progressive cardiomegaly,
      arrhythmia, thromboembolic events and heart failure. These symptoms suggest a
      persistent association with the presence of inflammatory infiltrate and tissue,
      and cellular destruction in the heart muscle. Nevertheless, few research studies
      have attempted to understand the role of inflammatory cells, such as neutrophils,
      in establishing the pathology and progression of CD. Only recently have some
      studies been performed with this intention. Despite this effort, the role of
      neutrophils in CD is still considered controversial. This review discusses the
      morphological and functional characteristics of neutrophils that describes their
      participation in the establishment and progression of Trypanosoma cruzi
      infection, through the development of its effector functions, such as release of
      lithic components, production of oxidative agents and release of inflammatory
      mediators capable of modulating the host immune response.

PMID- 30276824
TI  - Gonyaulax whaseongensis sp. nov. (Gonyaulacales, Dinophyceae), a new phototrophic
      species from Korean coastal waters.
AB  - The planktonic phototrophic dinoflagellate Gonyaulax whaseongensis sp. nov.,
      isolated from coastal waters of western Korea, was described from living and
      fixed cells under light and scanning electron microscopy, and its rDNA was
      sequenced. Gonyaulax whaseongensis had a plate formula of 2pr, 4', 6'', 6c, 6''',
      1p, and 1'''' with S-type ventral organization like the other species in the
      genus. However, this dinoflagellate had a narrow cingulum (ca. 2.6 MUm), small
      displacement of the cingulum, slight overhang and steep angle between the ends of
      the cingulum, quadrangular sixth precingular plate, reticulated cell surface
      without longitudinal lines or ridges, and two unequal antapical spines, together
      which distinguish this from all other reported Gonyaulax species. In addition,
      the SSU and LSU rDNA sequences were 8%-12% and 11%-24%, respectively, different
      from those of Gonyaulax polygramma, Gonyaulax spinifera, Gonyaulax fragilis,
      Gonyaulax membranacea, and Gonyaulax digitale, the putatively closest related
      species in the phylogenetic analysis.

PMID- 30276825
TI  - CAD1 and CCR2 protein complex formation in monolignol biosynthesis in Populus
      trichocarpa.
AB  - Lignin is the major phenolic polymer in plant secondary cell walls and is
      polymerized from monomeric subunits, the monolignols. Eleven enzyme families are
      implicated in monolignol biosynthesis. Here, we studied the functions of members
      of the cinnamyl alcohol dehydrogenase (CAD) and cinnamoyl-CoA reductase (CCR)
      families in wood formation in Populus trichocarpa, including the regulatory
      effects of their transcripts and protein activities on monolignol biosynthesis.
      Enzyme activity assays from stem-differentiating xylem (SDX) proteins showed that
      RNAi suppression of PtrCAD1 in P. trichocarpa transgenics caused a reduction in
      SDX CCR activity. RNAi suppression of PtrCCR2, the only CCR member highly
      expressed in SDX, caused a reciprocal reduction in SDX protein CAD activities.
      The enzyme assays of mixed and coexpressed recombinant proteins supported
      physical interactions between PtrCAD1 and PtrCCR2. Biomolecular fluorescence
      complementation and pull-down/co-immunoprecipitation experiments supported a
      hypothesis of PtrCAD1/PtrCCR2 heterodimer formation. These results provide
      evidence for the formation of PtrCAD1/PtrCCR2 protein complexes in monolignol
      biosynthesis in planta.

PMID- 30276827
TI  - Re-imagining occupational wellbeing: Development of an evidence-based framework.
AB  - BACKGROUND/AIM: Occupational therapists concern themselves with understanding
      engagement in everyday activity as a mode of facilitating wellbeing. However,
      there appears to be little consensus within the literature as to how engagement
      in meaningful activities contributes to wellbeing. Currently, there are no
      published evidence-based frameworks for wellbeing to support occupational therapy
      practitioners to address wellbeing with clients. The purpose of the study was to
      establish an evidence-based contemporary framework, domains and descriptive
      statements defining occupational wellbeing. METHODS: A multiphase, exploratory
      sequential mixed methods design, using both qualitative and quantitative
      approaches was used. Two phases were identified for data collection. The first
      phase involved exploration of the domains of occupational wellbeing, through
      conducting a literature review and two focus groups. The Delphi technique was
      employed in the second phase to refine and corroborate the domains of
      occupational wellbeing with an expert panel. RESULTS: Six new domains of
      occupational wellbeing were generated in the first phase of the study, namely:
      Competence, autonomy, contentment and pleasure, identity, hope and belonging. In
      the second phase, five out of the six domains reached a consensus level of 70% or
      more. Hope was the only domain not to reach consensus. CONCLUSION: The framework
      for occupational wellbeing produced by this study was created using evidence
      based, replicable methodology and garnered support from a highly regarded expert
      key informant group of occupational therapy and occupational science academics.
      Further exploration to determine whether there is widespread support and
      applicability for these domains with normative and vulnerable population groups
      is required.

PMID- 30276826
TI  - Bronchiolitis needs a revisit: Distinguishing between virus entities and their
      treatments.
AB  - Current data indicate that the "bronchiolitis" diagnosis comprises more than one
      condition. Clinically, pathophysiologically, and even genetically three main
      clusters of patients can be identified among children suffering from severe
      bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)
      induced bronchiolitis, characterized by young age of the patient, mechanical
      obstruction of the airways due to mucus and cell debris, and increased risk of
      recurrent wheezing. For this illness, an effective prophylactic RSV-specific
      monoclonal antibody is available; (b) rhinovirus-induced wheezing, associated
      with atopic predisposition of the patient and high risk of subsequent asthma
      development, which may, however, be reversed with systemic corticosteroids in
      those with severe illness; and (c) wheeze due to other viruses,
      characteristically likely to be less frequent and severe. Clinically, it is
      important to distinguish between these partially overlapping patient groups as
      they are likely to respond to different treatments. It appears that the first
      episode of severe bronchiolitis in under 2-year-old children is a critical event
      and an important opportunity for designing secondary prevention strategies for
      asthma. As data have shown bronchiolitis cannot simply be diagnosed using a
      certain cutoff age, but instead, as we suggest, using the viral etiology as the
      differentiating factor.

PMID- 30276828
TI  - Bursting strength of surgeon's and self-locking knots for closure of ventral
      midline celiotomy in horses.
AB  - OBJECTIVE: To compare the bursting strength and failure mode of ventral midline
      celiotomy closed with a simple continuous suture pattern with 1 of 2 knot
      combinations, a novel self-locking knot combination of a forwarder start with an
      Aberdeen end knot (F-A) and a traditional combination of a surgeon's start with a
      surgeon's end knot (S-S). STUDY DESIGN: Ex vivo experimental. SAMPLE POPULATION:
      Equine cadavers (n = 14). METHODS: A 20-cm ventral midline celiotomy was created
      in 14 equine cadavers. Horses were assigned to celiotomy closure with an F-A or S
      S knot combination. Prior to closure, a 200-L inflatable bladder was placed in
      the abdomen and then insufflated until failure of the celiotomy closure. The
      horses' signalment, weight, breed, and age, as well as knot combination type,
      mode of failure, closure time, and bursting strength (mm Hg) were recorded.
      RESULTS: The median bursting strength was significantly greater when incisions
      were closed with the F-A knot combination (388 mm Hg) compared with the S-S knot
      combination (290 mm Hg) (P = .035). Most incisions failed along the fascia when
      closed with F-A combinations and at the knot when closed with S-S combinations.
      CONCLUSION: The bursting strength of ventral midline incisions in equine cadavers
      was increased by an average of 25% when closed with the self-locking F-A knot
      combination. CLINICAL SIGNIFICANCE: Closing ventral midline celiotomies with an F
      A knot combination may provide a more secure closure than the traditional S-S
      knot combination. Additional in vivo investigation is required prior to
      recommending this closure in clinical cases.

PMID- 30276829
TI  - Response to AASLD editorial/message from the president.
AB  - A commentary [1] criticized our systematic review regarding the use of direct
      acting agents (DAAs) in chronic hepatitis C [2]. The following represents our
      major disagreements. Sustained virological response (SVR) is a non-validated
      surrogate outcome. The principles of evidence-based medicine require that it be
      validated in randomized clinical trials (RCTs) by showing parallel benefits in
      clinical outcomes [3]. This article is protected by copyright. All rights
      reserved.

PMID- 30276830
TI  - Pharmacokinetic studies of soyalkaloid A from Portulaca oleracea L. using ultra
      high-performance liquid chromatography electrospray ionization quadrupole-time of
      flight mass spectrometry and its antioxidant activity.
AB  - Soyalkaloid A was isolated from Portulaca oleracea L. for the first time in our
      laboratory and then a rapid and sensitive ultra-high-performance liquid
      chromatography electrospray ionization quadrupole-time of flight mass
      spectrometry (UHPLC-ESI-Q-TOF/MS) method with hesperidin as internal standard
      (IS) was developed and validated to investigate the pharmacokinetics of
      soyalkaloid A in rats after oral and intravenous administrations. The analysis
      was achieved on an Agilent Zorbax Eclipse Plus C18 Column (2.1 * 50 mm, 1.8 MUm)
      by elution with acetonitrile and water (containing 0.1% formic acid), at a flow
      rate of 0.3 mL/min. The MS analysis was performed in the positive ion mode with
      monitored ion m/z 227.0814 [M + H]+ and 611.1971 [M + H]+ for soyalkaloid A and
      IS, respectively. The linear range was established over the concentration range
      7.5-6000 ng/mL (r = 0.9951). The intra- and inter-assay accuracy and precision
      were between -4.86-4.49 and 1.93-9.66, respectively. The lower limits of
      detection and quantitation observed were 2.1 and 7.4 ng/mL, respectively. The
      rapid, sensitive and specific UHPLC-ESI-Q-TOF/MS method was successfully applied
      to a pharmacokinetic study of soyalkaloid A. Moreover, its antioxidant was
      studied via a 1,1-diphenyl-2-picryl-hydrazyl radical scavenging assay, the IC50
      value being 20.73 +/- 0.51 MUM.

PMID- 30276831
TI  - LncRNAnet: a comprehensive Sus scrofa lncRNA database.
AB  - Long noncoding RNAs (lncRNAs) constitute a large class of functional non-coding
      RNAs that play important roles in many biological processes. Thousands of lncRNAs
      have been identified in mammals. Pig is an important farm animal and biomedical
      model. It is essential to create a Sus scrofa lncRNA database to enable further
      study of the function and evolution of lncRNAs. In this study, we built a
      systematic S. scrofa lncRNA database named lncRNAnet that contains 53 468 S.
      scrofa lncRNAs with their sequence characteristics, genomic locations,
      conservation, overlapping SNPs and QTLs, and transcript abundance across nine
      tissues in pigs. We also integrated 212 922 human and mouse lncRNAs sequences
      into lncRNAnet. This database will provide for a systematic S. scrofa lncRNA
      classification and help investigators browse, search for and analyze lncRNAs as
      well as do blast searches among human, mouse and pig lncRNAs. Thus, lncRNAnet
      should improve the understanding of the biological functions of lncRNA. The
      database is freely accessible at http://lnc.rnanet.org/.

PMID- 30276833
TI  - Study on bioequivalence of beraprost in healthy volunteers by liquid
      chromatography with tandem mass spectrometry.
AB  - Beraprost sodium is an oral prostacyclin analog that was first approved in 1992
      (Japan) for the treatment of peripheral vascular disorders. It is administered
      orally as a tablet available in strength 20 MUg. In this paper, we described a
      liquid chromatography tandem mass spectrometry method that was developed for the
      quantification of beraprost in human plasma with high sensitivity at picogram per
      milliliter concentration. The method had been validated in terms of selectivity,
      sensitivity, accuracy and precision, matrix effect, linearity, recovery and carry
      over according to the Guideline on Bioanalytical Validation from the European
      Medicines Agency. The standard calibration curve for beraprost was 9.5-1419
      pg/mL. This method has been applied successfully to a bioequivalence study with
      60 MUg of beraprost (three tablets) in 29 healthy volunteers. The results showed
      that the two formulations of beraprost are bioequivalent.

PMID- 30276832
TI  - Meta-Analysis of Genetic Influences on Initial Alcohol Sensitivity.
AB  - BACKGROUND: Previous studies indicate that low initial sensitivity to alcohol may
      be a risk factor for later alcohol misuse. Evidence suggests that initial
      sensitivity is influenced by genetic factors, but few molecular genetic studies
      have been reported. METHODS: We conducted a meta-analysis of 2 population-based
      genome-wide association studies of the Self-Rating of the Effects of Alcohol
      scale. Our final sample consisted of 7,339 individuals (82.3% of European
      descent; 59.2% female) who reported having used alcohol at least 5 times. In
      addition, we estimated single nucleotide polymorphism (SNP)-based heritability
      and conducted a series of secondary aggregate genetic analyses. RESULTS: No
      individual locus reached genome-wide significance. Gene and set based analyses,
      both overall and using tissue-specific expression data, yielded largely null
      results, and genes previously implicated in alcohol problems and consumption were
      overall not associated with initial sensitivity. Only 1 gene set, related to
      hormone signaling and including core clock genes, survived correction for
      multiple testing. A meta-analysis of SNP-based heritability resulted in a modest
      estimate of  CONCLUSIONS: Findings yielded only modest support for a genetic
      component underlying initial alcohol sensitivity. Results suggest that its
      biological underpinnings may diverge somewhat from that of other alcohol outcomes
      and may be related to core clock genes or other aspects of hormone signaling.
      Larger samples, ideally of prospectively assessed samples, are likely necessary
      to improve gene identification efforts and confirm the current findings.

PMID- 30276834
TI  - Amniotic fluid cell-free DNA in preterm prelabor rupture of membranes.
AB  - INTRODUCTION: We evaluated the levels of cell-free nuclear DNA (nDNA) and cell
      free mitochondrial DNA (mtDNA) in the amniotic fluid supernatant from pregnancies
      complicated by preterm prelabor rupture of membranes (PPROM) based on evidence of
      microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic
      inflammation (IAI). MATERIAL AND METHODS: A total of 155 women with PPROM were
      included in this study. Amniotic fluid samples were obtained by transabdominal
      amniocentesis. The levels of cell-free nDNA and mtDNA in the amniotic fluid
      supernatant were assessed and quantified by real-time polymerase chain reaction.
      RESULTS: The levels of cell-free nDNA and mtDNA were higher in women with MIAC
      and IAI than in women without these conditions (nDNA: with MIAC: median 3.9 * 104
      genome equivalent [GE]/mL vs without MIAC: median 1.2 * 104  GE/mL, with IAI:
      median: 5.3 * 104  GE/mL vs without IAI: median 1.2 * 104  GE/mL; mtDNA: with
      MIAC: median 9.2 * 105  GE/mL vs without MIAC: median 2.5 * 105  GE/mL, with IAI:
      median 1.1 * 106  GE/mL vs without IAI: median 2.5 * 105 ; all P values <= 0.01).
      Women with the microbial-associated IAI showed the highest levels of cell-free
      nDNA and mtDNA. CONCLUSIONS: Cell-free nDNA and mtDNA are constituents of the
      amniotic fluid supernatant from PPROM pregnancies. Both cell-free nDNA and mtDNA
      are involved in the intra-amniotic inflammatory response in women with PPROM.

PMID- 30276835
TI  - Antiviral compound screening, peptide designing, and protein network construction
      of influenza a virus (strain a/Puerto Rico/8/1934 H1N1).
AB  - Hit, Lead & Candidate Discovery Plant-based antiviral therapy is the current need
      for holistic health care management, which can be achieved through screening of
      phytochemicals and designing of antiviral peptides. There exist certain host's
      factors which are directly involved for rapid viral replication causing worldwide
      pandemic. A total of 177 phytochemicals from Ocimum sanctum (L.), Tinospora
      cordifolia (Thunb.) Miers, Cinnamomum camphora (L.) J. Presl., Allium sativum
      (L.), Curcuma longa (L.), and Aloe vera (L.) Burm. f. were evaluated for their
      affinity to all viral proteins of H1N1. Applying drug filters and keeping the
      threshold of such filters relative to the standards, 82 compounds were found
      suitable for further analysis. Consensus scoring system was used for screening
      top ligands from 82 compounds, which screened the top 12 compounds. Highly
      conserved regions (>80%) which were hydrophilic, flexible, antigenic, and also
      charged were screened out as potent antiviral peptides. The viral proteins were
      taken as the targets for the modeled peptides for protein-protein docking.
      Further, host-pathogen interacting network was constructed to unveil host factors
      involved in viral replication, from which unique protein clusters representing
      their involvement in viral reproduction were selected through mapping with
      pathway databases. Twelve compounds and five peptides were found to be highly
      effective against all the proteins of H1N1. Based on the uniqueness, 13 clusters
      of proteins were obtained which are engaged in cellular process, namely, viral
      reproduction, fructose-6-phosphate metabolism, nitrogen compound metabolism,
      biosynthesis, cellular process, oligodendrocyte development, localization,
      multiorganism process, primary metabolism, response to unfolded protein,
      metabolism, and response to protein and catabolism.

PMID- 30276836
TI  - A frameshift variant in the EDA gene in Dachshunds with X-linked hypohidrotic
      ectodermal dysplasia.
AB  - X-linked hypohidrotic ectodermal dysplasia (XLHED) is a genetic disease
      characterized by hypoplasia or absence of hair, teeth and sweat glands. The EDA
      gene, located on the X chromosome, encodes the type II transmembrane protein
      ectodysplasin A. Variants in the EDA gene can lead to XLHED in humans, mice,
      cattle and dogs. In the present study, we investigated a litter of Dachshund
      puppies, of which four male puppies showed clinical signs of XLHED. We performed
      a candidate gene analysis in one affected puppy and several non-affected
      relatives. This analysis revealed a single base-pair deletion in the coding
      sequence of the EDA gene in the affected puppy (NM_001014770.2:c.842delT). The
      deletion is predicted to cause a frameshift, NP_001014770.1:p.(Leu281HisfsTer22),
      leading to a premature stop codon which truncates more than one quarter of the
      EDA protein. Sanger sequencing results confirmed that this variant was inherited
      from the dam. Based on knowledge about the functional impact of EDA variants in
      dogs and other species, c.842delT is a convincing candidate causative variant for
      the observed XLHED in the male puppies.

PMID- 30276837
TI  - Antiallodynic interaction and motor performance of the pregabalin/thioctic acid
      and pregabalin/alpha-tocopherol combinations in neonatal streptozotocin-induced
      diabetic rats.
AB  - Painful peripheral neuropathy can be associated with nerve damage caused by
      diabetes mellitus. Although pregabalin is the first-line therapy for peripheral
      neuropathy, it shows substantial discontinuation rates, mainly because of nervous
      system side effects as motor incoordination. Multimodal therapy may improve the
      motor side effect profile of pregabalin. The aim of this study was to evaluate
      the interaction of pregabalin + thioctic acid or pregabalin + alpha-tocopherol on
      allodynia and motor performance in neonatal streptozotocin-induced diabetic rats.
      Efficacy of drugs separately or in combination was tested by tactile allodynia
      using von Frey filaments. Isobolographic and interaction index analysis were used
      to determine the antiallodynic interaction between pregabalin and either thioctic
      acid or alpha-tocopherol. Motor performance was measured using a rotarod test.
      Pregabalin, thioctic acid, and alpha-tocopherol reduced, in a dose-dependent
      fashion, tactile allodynia. Pregabalin + thioctic acid and pregabalin + alpha
      tocopherol combinations also dose-dependently reduced allodynic behavior in
      diabetic rats. Isobolographic analysis revealed an additive interaction for both
      combinations. Consistently, the interaction indices confirmed the additive effect
      between pregabalin + thioctic acid and pregabalin + alpha-tocopherol. In
      addition, the administration of either combination improved motor incoordination
      induced by pregabalin. Data suggests that thioctic acid or alpha-tocopherol could
      positively impact the therapeutic profile of pregabalin, because they might be
      useful for reducing motor incoordination associated to pregabalin in patients
      with peripheral neuropathy.

PMID- 30276838
TI  - Curcumin potentiates the fungicidal effect of dodecanol by inhibiting drug efflux
      in wild-type budding yeast.
AB  - Drug resistance commonly occurs when treating immunocompromised patients who have
      fungal infections. Curcumin, is a compound isolated from Curcuma longa, has been
      reported to inhibit drug efflux in several human cell lines and nonpathogenic
      budding yeast Saccharomyces cerevisiae cells that overexpresses the ATP-binding
      cassette (ABC) transporters S. cerevisiae Pdr5p and pathogenic Candida albicans
      Cdr1p and Cdr2p. The aim of this study was to examine the effects of curcumin on
      multidrug resistance in a wild-type strain of the budding yeast with an intrinsic
      expression system of multidrug efflux-related genes. The antifungal activity of
      dodecanol alone was temporary against S. cerevisiae; however, restoration of cell
      viability was completely inhibited when the cells were co-treated with dodecanol
      and curcumin. Furthermore, restriction of rhodamine 6G (R6G) efflux from the
      cells and intracellular accumulation of R6G were observed with curcumin
      treatment. Reverse transcription-polymerase chain reaction analysis revealed that
      curcumin reduced the dodecanol-induced overexpression of the ABC transporter
      related genes PDR1, PDR3 and PDR5 to their control levels in untreated cells.
      Curcumin can directly restrict the glucose-induced drug efflux and inhibits the
      expression of the ABC transporter gene PDR5, and can thereby inhibit the efflux
      of dodecanol from S. cerevisiae cells. Curcumin is effective in potentiating the
      efficacy of antifungal drugs via its effects on ABC transporters. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Drug resistance is common in immunocompromised patients
      with fungal infections. Curcumin, isolated from Curcuma longa, inhibits drug
      efflux in nonpathogenic budding yeast Saccharomyces cerevisiae cells
      overexpressing ABC transporters S. cerevisiae Pdr5p and pathogenic Candida
      albicans Cdr1p and Cdr2p. We examined the effects of curcumin on multidrug
      resistance in a wild-type strain of the budding yeast with an intrinsic
      expression system of multidrug efflux-related genes. Curcumin directly inhibited
      drug efflux and also suppressed the PDR5 expression, thereby enhancing the
      antifungal effects. Thus, curcumin potentially promotes the efficacy of
      antifungals via its effects on ABC transporters in wild-type fungal strains.

PMID- 30276839
TI  - Matched or unmatched analyses with propensity-score-matched data?
AB  - Propensity-score matching has been used widely in observational studies to
      balance confounders across treatment groups. However, whether matched-pairs
      analyses should be used as a primary approach is still in debate. We compared the
      statistical power and type 1 error rate for four commonly used methods of
      analyzing propensity-score-matched samples with continuous outcomes: (1) an
      unadjusted mixed-effects model, (2) an unadjusted generalized estimating method,
      (3) simple linear regression, and (4) multiple linear regression. Multiple linear
      regression had the highest statistical power among the four competing methods. We
      also found that the degree of intraclass correlation within matched pairs depends
      on the dissimilarity between the coefficient vectors of confounders in the
      outcome and treatment models. Multiple linear regression is superior to the
      unadjusted matched-pairs analyses for propensity-score-matched data.

PMID- 30276840
TI  - Dopamine D2 receptors in the basolateral amygdala modulate erectile function in a
      rat model of nonorganic erectile dysfunction.
AB  - Nonorganic erectile dysfunction is a problem with unknown central mechanisms.
      Changes in brain activity in the amygdala have been observed in human patients.
      This study aimed to investigate the dopamine system in the basolateral amygdala
      of male rats with nonorganic erectile dysfunction. We applied chronic mild stress
      to induce nonorganic erectile dysfunction. After exposure to chronic mild stress,
      the sucrose consumption test, sexual behaviour test and apomorphine test were
      used to select depression-like rats with erectile dysfunction as nonorganic
      erectile dysfunction model rats. The sexual behaviour of these rats after central
      infusion of a dopamine D1/D2 receptor agonist/antagonist was observed. The
      expression levels of dopamine D1/D2 receptors and tyrosine hydroxylase in the
      basolateral amygdala were also measured. The result of the sucrose consumption
      test, sexual behaviour test and apomorphine test indicated a successful
      nonorganic erectile dysfunction model. Central infusion of a dopamine D2 receptor
      agonist increased intromission ratio in model rats. Lower expression levels of
      tyrosine hydroxylase and the dopamine D2 receptor in the basolateral amygdala
      were observed in rats with nonorganic erectile dysfunction. These results suggest
      that impairment of the dopamine D2 receptor pathway in the basolateral amygdala
      may contribute to the development of nonorganic erectile dysfunction.

PMID- 30276841
TI  - Schistosomiasis (bilharziasis) and male infertility.
AB  - Schistosomiasis (bilharziasis) is an endemic parasitic disease of a major source
      of morbidity and mortality for developing countries. It is caused by different
      species of blood flukes (trematode worms) of the genus Schistosoma, the most
      important of which are S. haematobium which infests the genitourinary tract and
      S. mansoni and S. japonicum which infest the gastrointestinal tract. The
      incidence of schistosome-induced male infertility is not known and probably
      underestimated being overshadowed by the more severe and often fatal urinary and
      gastrointestinal complications. Several causes may contribute to schistosomiasis
      induced male infertility, such as hormonal imbalance, testicular tissue damage
      and genital ductal system obstruction, in addition to decreased libido and
      erectile dysfunction due to associated hormonal imbalance and prostatic
      infestation. Demonstration of the schistosome ova in seminal plasma or testicular
      tissue confirms the diagnosis. Treatment of schistosomiasis-induced male
      infertility depends on clinical evaluation and includes, besides anthelmintic
      treatment, hormonal replacement and assisted reproduction (IVF/ICSI) in cases of
      severe oligozoospermia and or obstructive and nonobstructive azoospermia.

PMID- 30276842
TI  - Access to a school health nurse and adolescent health needs in the universal
      school health service in Finland.
AB  - Universal school health services are expected to offer similar, needs-based
      services to all students across schools, service providers and students' socio
      economic statuses and health needs. This study investigates access to school
      health nurses in Finland. The objectives were to study the differences in access
      to school health nurse between service providers, schools, students'
      characteristics and school health nurse resources. Access was examined through a
      nationwide School Health Promotion study, which is a self-reporting, voluntary
      and anonymous survey for 8th and 9th graders (15 to 16-year old, N = 71865). The
      ethical committee of the National Institute for Health and Welfare has approved
      procedure for the School Health Promotion study. Data on school health nurse
      resources and service providers were obtained from the national database (534
      schools; 144 service providers). Multilevel logistic regression was used. Of the
      pupils, 15% of girls and 11% of boys reported difficult access to a school health
      nurse. The number of adolescents who reported difficult access ranged between
      service providers (0%-41%) and schools (0%-75%). Students with lower socio
      economic background, poorer well-being at school, lack of support for studying
      and greater health needs reported difficult access more often. School health
      nurse resources were associated with difficult access only among boys, when
      resources were under the national recommendations. These findings raise concern
      about equality and unmet health needs in school health services.

PMID- 30276843
TI  - Exposure to Plasmodium vivax is associated with the increased expression of
      exhaustion markers on gammadelta T lymphocytes.
AB  - Gamma delta (gammadelta) T cells exhibit potent anti-Plasmodium activity but are
      also implicated in the immunopathology of malaria. It is currently poorly
      understood how gammadelta T cells are affected in human suffering from Plasmodium
      vivax infection or in symptomless individuals living in an endemic region. We
      examined both the percentages and expression of markers associated with immune
      exhaustion in gammadelta T cells in individuals living in a P. vivax endemic
      region by flow cytometry. The percentage of gammadelta T cells in the blood was
      significantly higher both in acute P. vivax-positive patients and in individuals
      from an endemic region in comparison with control uninfected adults. The
      frequency of the expression of the exhaustion markers-Tim-3, Lag-3, CTLA-4 and PD
      1 was higher in gammadelta and total T cells from P. vivax-infected patients than
      in those populations from control uninfected adults. Individuals from a P. vivax
      endemic region showed elevated percentages of Tim-3-, Lag-3- and CTLA-4-positive
      gammadelta T cells and an increased percentage of Tim-3-positive total T cells.
      The phenotypic exhaustion of these cells might be a protective mechanism
      preventing the immunopathology associated with activated T cells and may provide
      a rationale for targeted manipulation of this process in diseases such as
      malaria.

PMID- 30276844
TI  - Genome-wide association study and heritability estimate for ectopic ureters in
      Entlebucher mountain dogs.
AB  - An ectopic ureter is a congenital anomaly which may lead to urinary incontinence
      and without a surgical intervention even to end-stage kidney disease. A genetic
      component contributes to the development of this anomaly in Entlebucher mountain
      dogs (EMD); however, its nature remains unclear. Using the Illumina CanineHD bead
      chip, a case-control genome-wide association study was performed to identify SNPs
      associated with the trait. Six loci on canine chromosomes 3, 17, 27 and 30 were
      identified with 16 significantly associated SNPs. There was no single outstanding
      SNP associated with the phenotype, and the association signals were not close to
      known genes involved in human congenital anomalies of the kidney or lower urinary
      tract. Additional research will be necessary to elucidate the potential role of
      the associated genes in the development of ectopic ureters in the EMD breed.

PMID- 30276845
TI  - Difference in the seminal plasma protein expression in unexplained infertile men
      with successful and unsuccessful in vitro fertilisation outcome.
AB  - Unexplained male infertility (UMI) is a condition in which routine semen analysis
      fails to detect subcellular sperm dysfunctions. In the present research, a
      comparative proteomics study of seminal plasma (SP) was conducted in men with
      unexplained infertility whose female partners had undergone in vitro
      fertilisation (IVF) treatment to find differences in the SP protein profile. Five
      UMI men with successful and eight with unsuccessful IVF outcome enrolled in this
      study. Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) technique was
      used for protein separation. The differentially expressed proteins were
      identified using mass spectrometry. Results indicated that at least two different
      protein spots, including clusterin and epididymal secretory protein E1, were over
      expressed (1.5- and 2-fold change, respectively, p < 0.05) while prostate
      specific antigen was downregulated (0.3-fold change, p < 0.05) in the successful
      group as compared with the unsuccessful group. Considering the role of all three
      identified proteins in the sperm quality, the results of the present study
      introduced these proteins as new candidate biomarkers for success of IVF in UMI
      couples.

PMID- 30276846
TI  - Effect of chrysin on methotrexate-induced testicular damage in rats.
AB  - This study was conducted on 28 male Wistar albino rats to determine the effects
      of chrysin on methotrexate-induced damage to testicular tissue. Rats were grouped
      into four groups of seven rats reach: Group 1 (n = 7) was the control group to
      which no drugs were administered; this group was only provided with food and
      water. Group 2 (n = 7) was administered 20 mg/kg of methotrexate once
      intraperitoneally. Group 3 (n = 7) was administered 50 mg/kg of chrysin for 7
      days orally. Group 4 (n = 7) was administered 20 mg/kg of methotrexate once
      intraperitoneally, followed by oral administration of 50 mg/kg of chrysin for 7
      days. At the end of the experiment, rats were anaesthetised, rat testes were
      removed, and spermatozoon was obtained from the cauda epididymis. It was
      determined that sperm count and motility, glutathione peroxidase, superoxide
      dismutase and catalase activities decreased in the methotrexate group, whereas
      malondialdehyde, tumour necrosis factor-alpha, interleukin-1beta and nuclear
      kappa factor B expression levels increased. Furthermore, damage to tubulus
      seminiferus structures and affusion in germ cells was identified. In the
      methotrexate + chrysin administered group, sperm count improved, biochemical
      enzyme levels increased, and structural improvements were observed in testicular
      tubules. These findings demonstrated that chrysin plays a protective role in
      testicular damage in rats.

PMID- 30276847
TI  - Humanising patient care through student eyes.

PMID- 30276848
TI  - Statistical Learning Is Not Age-Invariant During Childhood: Performance Improves
      With Age Across Modality.
AB  - Humans are capable of extracting recurring patterns from their environment via
      statistical learning (SL), an ability thought to play an important role in
      language learning and learning more generally. While much work has examined
      statistical learning in infants and adults, less work has looked at the
      developmental trajectory of SL during childhood to see whether it is fully
      developed in infancy or improves with age, like many other cognitive abilities. A
      recent study showed modality-based differences in the effect of age during
      childhood: While visual SL improved with age, auditory SL did not. This finding
      was taken as evidence for modality-based differences in SL. However, since that
      study used auditory linguistic stimuli (syllables), the differential effect of
      age may have been driven by stimulus type (linguistic vs. non-linguistic) rather
      than modality. Here, we ask whether age will affect performance similarly in the
      two modalities when non-linguistic auditory stimuli are used (familiar sounds
      instead of syllables). We conduct a large-scale study of children's performance
      on visual and non-linguistic auditory SL during childhood (ages 5-12 years). The
      results show a similar effect of age in both modalities: Unlike previous
      findings, both visual and non-linguistic auditory SL improved with age. These
      findings highlight the stimuli-sensitive nature of SL and suggest that modality
      based differences may be stimuli-dependent, and that age-invariance may be
      limited to linguistic stimuli.

PMID- 30276849
TI  - Influence of the extracellular matrix on water mobility in subcortical gray
      matter.
AB  - PURPOSE: Water mobility in tissues is related to the microstructure that
      modulates diffusion and spin relaxation. Previous work has shown that the
      extracellular matrix (ECM) impacts water diffusion in cartilage. To investigate
      if similar contributions to image contrast exist for brain, which is
      characterized by a substantially lower ECM content, diffusion and relaxation were
      studied in fixed samples from goat and human thalamus before and after enzymatic
      digestion of ECM compounds. Selected experiments in human corpus callosum were
      included for comparing subcortical gray matter and white matter. METHODS:
      Digestion of matrix components was achieved by treatment with hyaluronidase.
      Nonlocalized pulsed field gradient measurements were performed with  RESULTS:
      Microstructural alterations associated with hyaluronan digestion did not lead to
      measurable effects on water diffusion or  CONCLUSION: Investigations with very
      strong gradients did not reveal a detectable effect on water diffusion or 

PMID- 30276850
TI  - Training specialists as consultants integrated into primary care.

PMID- 30276851
TI  - Red to green pigment change noted in plasma of patient undergoing therapeutic
      plasma exchange for Goodpasture syndrome.

PMID- 30276853
TI  - Effect of flow-encoding strength on intravoxel incoherent motion in the liver.
AB  - PURPOSE: To study the impact of variable flow-encoding strength on intravoxel
      incoherent motion (IVIM) liver imaging of diffusion and perfusion. THEORY: Signal
      attenuation in DWI arises from (1) intravoxel microvascular blood flow, which
      depends on the flow-encoding strength alpha (first gradient moment) of the
      diffusion-encoding waveform, and (2) intravoxel spin diffusion, which depends on
      the b-value of the diffusion-encoding gradient waveforms alpha and b-value. Both
      are linked to the diffusion-encoding gradient waveform and conventionally are not
      independently controlled. METHODS: In this work a convex optimization framework
      was used to generate gradient waveforms with independent alpha and b-value.
      Thirty-six unique alpha and b-value sample points from 5 different gradient
      waveforms were used to reconstruct perfusion fraction (f), coefficient of
      diffusion (D), and blood velocity standard deviation (Vb ) maps using a recently
      proposed IVIM model. Faster acquisition strategies were evaluated with 1000
      random subsampling strategies of 16, 8, and 4 alpha and b-value. Among the
      subsampled reconstructions, the sampling schemes that minimized the difference
      with the fully sampled reconstruction were reported. RESULTS: Healthy volunteers
      (N = 9) were imaged on a 3T scanner. Liver perfusion and diffusion estimates
      using the fully sampled IVIM method were f = 0.19 +/- 0.06, D = 1.15 +/- 0.15 
      CONCLUSION: We demonstrate the IVIM signal's dependence on the b-value, the
      diffusion-encoding time and the flow-encoding strength and observe in vivo the
      ballistic regime signature of microperfusion in the liver. This work also
      demonstrates that using an IVIM model and sampling scheme matched to the
      ballistic regime, pixel-wise IVIM parameter maps are possible when sampling as
      few as 4 IVIM signals.

PMID- 30276854
TI  - Concise synthesis and antibacterial evaluation of novel 3-(1,4-disubstituted
      1,2,3-triazolyl)uridine nucleosides.
AB  - We report herein a simple and efficient synthesis of a new series of
      antibacterial uridine nucleosides. The strategy involved a sequential
      silylation/N-glycosylation/N-propargylation procedure of uracil 1 for preparing
      the dipolarophile 5 in good yield. A series of novel uridine-[1,2,3]triazole
      nucleosides 6a-j were efficiently synthesized via the copper-catalyzed azide
      alkyne cycloaddition (CuAAC) from dipolarophile 5 with different selected azides.
      The reactions were carried out under both conventional and ultrasonic irradiation
      conditions. In general, improvements were observed when reactions were carried
      out under sonication. Their antibacterial potential has been evaluated by means
      of a micro-dilution assay against either Gram-positive or Gram-negative bacteria.
      Compounds 6i and 6j have shown significant bactericidal activity against
      Staphylococcus aureus (MIC = 10 and 6 MUM, respectively), and 6h against
      Escherichia coli (MIC = 8 MUM). Moreover, antibacterial kinetic assays showed
      that 6i and 6j significantly reduced the S. aureus growth rate at the MIC
      concentration, after 6 h, compared to their deprotected analogs, 6k and 6l,
      respectively. Compound 6h also significantly reduced the growth of E. coli. These
      antibacterial effects may be related to the penetrating properties of these
      compounds, as revealed by the leakage of nucleic acids from the sensitive
      strains.

PMID- 30276855
TI  - Optical coherence tomography angiography findings in a case of adult-onset
      vitelliform dystrophy.

PMID- 30276856
TI  - Resident and attending perceptions of direct observation in internal medicine: a
      qualitative study.
AB  - OBJECTIVES: Direct observation is the foundation of assessment and learning in
      competency-based medical education (CBME). Despite its importance, there is
      significant uncertainty about how to effectively implement frequent and high
      quality direct observation. This is particularly true in specialties where
      observation of non-procedural skills is highly valued and presents unique
      challenges. It is therefore important to understand perceptions of direct
      observation to ensure successful acceptance and implementation. In this study, we
      explored perceptions of direct observation in internal medicine. METHODS: We
      interviewed internal medicine attending physicians (n = 9) and residents (n = 8)
      at the University of Toronto, purposively sampled for diversity. Using a
      constructivist grounded theory approach, constant comparative analysis was
      performed to develop a framework to understand perceptions of direct observation
      on the clinical teaching units. RESULTS: Participants articulated a narrow
      perception of what constitutes direct observation, in contrast to their own
      descriptions of skills that were observed. This resulted in the perception that
      certain valuable skills that participants felt were routinely observed were
      nonetheless not 'directly observable', such as clinical reasoning, observed
      through case presentations and patient care discussions. Differentiating direct
      observation from informal observation led to overestimation of the time and
      resource requirements needed to enhance direct observation, which contributed to
      scepticism and lack of engagement related to CBME implementation. CONCLUSIONS: In
      an internal medicine training programme, perceptions of what constitutes direct
      observation can lead to under-recognition and hinder acceptance in workplace
      based assessment and learning. Our results suggest a reframing of 'direct
      observation' for residents and attending physicians, by explicitly identifying
      desired skills in non-procedurally-based specialties. These findings may help
      CBME-based training programmes improve the process of direct observation, leading
      to enhanced assessment and learning.

PMID- 30276857
TI  - Reply from the authors: Additional factors to consider with regard to
      condensation in bench studies.

PMID- 30276858
TI  - Validation of the inflammatory bowel disease disability index for self-report and
      development of an item-reduced version.
AB  - BACKGROUND AND AIM: The Inflammatory Bowel Disease Disability Index (IBD-DI) is a
      measure of disability in inflammatory bowel disease (IBD). The IBD-DI is
      validated for use as a clinical interview but not for use as a self-report
      questionnaire. We aimed to validate the IBD-DI for self-report (IBD-DI-SR) and to
      reduce the number of items, using IBD patients from two centers. METHODS: Between
      April and August 2017, ambulatory IBD patients were recruited from Christchurch
      Hospital, New Zealand and Concord Hospital, Australia. The IBD-DI clinical
      interview version was compared with a self-report version. Participants were
      randomized to do the clinical interview or self-report first. Validation of the
      IBD-DI-SR involved calculating the correlation coefficient between the clinician
      completed and self-reported version of the IBD-DI and Cronbach's alpha of
      internal consistency of the IBD-DI-SR. To create an item-reduced version,
      multiple linear regression was used. The R2 of the model described the overall
      association between the item-reduced IBD-DI-SR and the IBD-DI. RESULTS: One
      hundred fourteen patients (57 from Christchurch and 57 from Sydney) completed the
      IBD-DI-SR validation phase, of whom 63 had Crohn's disease and 51 had ulcerative
      colitis. The Pearson correlation coefficient between the IBD-DI-SR and IBD-DI is
      0.90 (P < 0.001), and Cronbach's alpha of the IBD-DI-SR was 0.86. The item
      reduced version of the IBD-DI-SR consisted of eight questions instead of 28,
      explaining 77% of the variance. CONCLUSIONS: The IBD-DI-SR has demonstrated
      reliability and validity. The item-reduced IBD-DI-SR is a concise self-report
      instrument for measuring IBD disability, which makes the IBD-DI more widely
      usable.

PMID- 30276859
TI  - Parental subfertility is associated with higher blood pressure in offspring.

PMID- 30276860
TI  - Lower respiratory tract infections appear to be the most important risk factor
      for current asthma in subarctic schoolchildren.
AB  - AIM: The aim of this study was to identify possible risk factors for current
      asthma revealed by two studies in Northern Norway in 1985 and 2008 and to
      evaluate these factors contribution to the increased prevalence of asthma over
      these 23 years. METHODS: As part of the 'Asthma and allergy study among
      schoolchildren in Nordland county' we performed a case-control study (70.0%
      attendance) comparing 153 children with current asthma (cases) to their non
      asthmatic controls. The results from this 2008 study were compared to a similar
      case-control study (93.2% attendance) performed in 1985 based on 62 current
      asthmatics. RESULTS: In 1985 the most important risk factors for current asthma
      were repeated lower respiratory tract infections (LRTIs) with adjusted odds ratio
      (aOR) 52.11, together with urticaria ever and atopic disease in the family. In
      2008 the most important risk factors were food allergy with aOR7.06, LRTIs during
      the first 3 years of life with aOR 5.80 and hospitalisation caused by LRTIs.
      CONCLUSION: In both studies, LRTI was the most important risk factor for current
      asthma. Whether or not LRTIs have contributed to the increased asthma prevalence
      in this population over 23 years is unresolved. This article is protected by
      copyright. All rights reserved.

PMID- 30276861
TI  - Snus users had high levels of nicotine, cotinine and 3-hydroxycotinine in their
      breastmilk, and the clearance was slower than in smoking mothers.
AB  - AIM: Using snus, an oral moist tobacco, has increased among pregnant women in
      Sweden, the only European Union country where sales are legal. This study
      evaluated whether snus generated similar concentrations of nicotine and its
      metabolites in breastmilk to cigarette smoking. METHODS: We analysed 49
      breastmilk samples from 33 nursing mother - 13 snus users, six cigarette smokers
      and 14 controls - for concentrations of nicotine, cotinine and 3-hydroxycotinine.
      The mothers were recruited at antenatal clinics in Sweden from 2007 to 2012.
      RESULTS: The median nicotine concentration in breastmilk of the snus users was
      38.7 ng/mL (0-137) versus 24.0 ng/mL (0-56) in smokers, with median cotinine
      levels of 327.6 ng/mL (37-958) versus 164.4 ng/mL and median 3-hydroxycotinine
      levels of 202.7 ng/mL (28-452) versus 112.4 (0-231), respectively. Nicotine was
      still detected in the breastmilk of eight of the 13 snus users after abstaining
      from tobacco for a median duration of 11 hours (0.6-12.5), while the breastmilk
      of the smokers was nicotine-free after four hours' abstinence. CONCLUSION: Snus
      users had high levels of nicotine and metabolites in their breastmilk and
      nicotine was found even after 12.5 hours of abstinence.

PMID- 30276862
TI  - Delayed calcineurin inhibitor introduction and renal outcomes in liver transplant
      recipients receiving basiliximab induction.
AB  - BACKGROUND: To investigate the impact of delayed calcineurin inhibitor (CNI)
      initiation in liver transplant recipients (LTR) with peri-operative renal
      insufficiency receiving basiliximab induction, we compared renal outcomes of LTR
      stratified by the degree of achieved post-operative renal recovery (RR) prior to
      CNI initiation. METHODS: All adult LTR transplanted between 01/2007 and 12/2015
      who received basiliximab were included. Patients who received multi-organ
      transplantations, were repeat transplant recipients, or expired prior to post
      operative day (POD) 90 were excluded. The primary outcome of our retrospective
      analysis was renal function at POD 90. RESULTS: A total of 210 patients were
      included in our final analysis. Most patients were Caucasian males undergoing
      liver transplantation for liver disease secondary to hepatitis C virus. Baseline
      characteristics were similar among the evaluable population. Estimated GFR was
      significantly higher among patients with the greatest degree of post-operative
      renal recovery at POD 90; however, this difference did not persist at POD 180.
      There was no significant difference in incidence or severity of biopsy-proven
      acute rejection (BPAR) at any measured time point. CONCLUSIONS: Delayed CNI
      initiation following liver transplantation in patients with post-operative renal
      insufficiency who receive basiliximab induction does not adversely affect the
      incidence of BPAR or long-term renal outcomes.

PMID- 30276863
TI  - Hollow Micro/Nanostructured Ceria-Based Materials: Synthetic Strategies and
      Versatile Applications.
AB  - Hollow micro/nanostructured CeO2 -based materials (HMNCMs) have triggered
      intensive attention as a result of their unique structural traits, which arise
      from their hollowness and the fascinating physicochemical properties of CeO2 .
      This attention has led to widespread applications with improved performance.
      Herein, a comprehensive overview of methodologies applied for the synthesis of
      various hollow structures, such as hollow spheres, nanotubes, nanoboxes, and
      multishelled hollow spheres, is provided. The synthetic strategies toward CeO2
      hollow structures are classified into three major categories: 1) well-established
      template-assisted (hard-, soft-, and in situ template) methods; 2) newly emerging
      self-template approaches, including selective etching, Ostwald ripening, the
      Kirkendall effect, galvanic replacement, etc.; 3) bottom-up self-organized
      formation synthesis (namely, oriented attachment and self-deformation). Their
      underlying mechanisms are concisely described and discussed in detail, the
      differences and similarities of which are compared transversely and
      longitudinally. Niche applications of HMNCMs in a wide range of fields including
      catalysis, energy conversion and storage, sensors, absorbents, photoluminescence,
      and biomedicines are reviewed. Finally, an outlook of future opportunities and
      challenges in the synthesis and application of CeO2 -based hollow structures is
      also presented.

PMID- 30276864
TI  - Predictors of biochemical recurrence after Retzius-sparing robot-assisted radical
      prostatectomy: Analysis of 359 cases with a median follow-up period of 26 months.
AB  - OBJECTIVES: Our aim was to evaluate the predictors of biochemical recurrence
      after Retzius-sparing robot-assisted radical prostatectomy. METHODS: The study
      cohort consisted of 359 consecutive non-metastatic prostate cancer patients who
      underwent Retzius-sparing robot-assisted radical prostatectomy between November
      2012 and January 2016. According to the National Comprehensive Cancer Network
      prostate cancer risk classification, 164 patients (45.7%) had high- or very high
      risk prostate cancer. No patient received adjuvant therapy until documented
      biochemical recurrence. Biochemical recurrence-free survival was estimated using
      the Kaplan-Meier method. Univariable and multivariable Cox proportional hazards
      regression models were used to determine variables predictive of biochemical
      recurrence. RESULTS: The median follow-up period was 26 months (interquartile
      range 19-38 months). The overall biochemical recurrence rate was 14.8%, and the
      median time to biochemical recurrence was 11 months (interquartile range 6-22
      months). The 3-year biochemical recurrence-free survival probability was 71.2%,
      72.1%, 88.7%, 82.3% and 95.7% in very high-, high-, intermediate-, low- and very
      low-risk prostate cancer, respectively (log-rank, P < 0.001). On multivariable
      analysis, preoperative prostate-specific antigen (hazard ratio 1.03, 95%
      confidence interval 1.02-1.04; P < 0.0001), percentage of maximum core
      involvement on biopsy (hazard ratio 1.02, 95% confidence interval 1.01-1.03; P =
      0.029) and clinical stage >=T3a (hazard ratio 2.12, 95% confidence interval 1.02
      4.39; P = 0.043) were predictors of biochemical recurrence, whereas pathological
      Gleason score >=8 (hazard ratio 5.63, 95% confidence interval 1.62-19.61; P =
      0.007) and pathological tumor volume (hazard ratio 1.08, 95% confidence interval
      1.04-1.20; P < 0.001) were the main pathological predictors of biochemical
      recurrence. CONCLUSIONS: Retzius-sparing robot-assisted radical prostatectomy
      confers effective biochemical recurrence control at the mid-term follow-up
      period. Preoperative prostate-specific antigen, advanced clinical stage and
      higher Gleason score were important predictors of biochemical recurrence after
      Retzius-sparing robot-assisted radical prostatectomy. Long-term oncological
      safety still needs to be established.

PMID- 30276865
TI  - Carer coping and resident agitation as predictors of quality of life in care home
      residents living with dementia: Managing Agitation and Raising Quality of Life
      (MARQUE) English national care home prospective cohort study.
AB  - OBJECTIVES: The objectives of the study are (1) to test our primary hypothesis
      that carers using more dysfunctional coping strategies predict lower quality of
      life in care home residents living with dementia, and this is moderated by levels
      of resident agitation, and (2) to explore relationships between carer
      dysfunctional coping strategy use, agitation, quality of life, and resident
      survival. METHODS: In the largest prospective cohort to date, we interviewed
      carers from 97 care home units (baseline, 4, 8, 12, 16 months) about quality of
      life (DEMQOL-Proxy) and agitation (Cohen-Mansfield Agitation Inventory) of 1483
      residents living with dementia. At baseline, we interviewed 1566 carers about
      coping strategies (Brief COPE), averaging scores across care home units. RESULTS:
      Carer dysfunctional coping strategies did not predict resident quality of life
      over 16 months (0.03, 95% CI -0.40 to 0.46). Lower resident quality of life was
      longitudinally associated with worse Cohen-Mansfield Agitation Inventory score (
      0.25, 95% CI -0.26 to -0.23). Survival was not associated with carer
      dysfunctional coping, resident quality of life, or agitation scores. CONCLUSIONS:
      Carer dysfunctional coping did not predict resident quality of life. Levels of
      resident agitation were consistently high and related to lower quality of life,
      over 16 months. Lack of association between carer dysfunctional coping and
      resident quality of life may reflect the influence of the care home or an
      insensitivity of aggregated coping strategy scores. The lack of relationship with
      survival indicates that agitation is not explained mainly by illness. Scalable
      interventions to reduce agitation in care home residents living with dementia are
      urgently needed.

PMID- 30276866
TI  - Long-term effect of migration background on the development of physical fitness
      among primary school children.
AB  - BACKGROUND: Children with a low socioeconomic status and migration background are
      more likely to exhibit unfavorable health behavior patterns and higher BMI scores
      as well as lower physical activity and physical fitness. AIM: To evaluate the
      effect of migration background on the development of physical fitness among
      primary school children from first to third grade. METHODS: In this longitudinal
      study, height, weight, and physical fitness of primary school children from
      Tyrol/Austria were measured five times over a period of 2.5 years using the
      German motor performance test DMT 6-18 consisting of eight items testing
      different subdomains of physical fitness. RESULTS: A total of 266 children (45%
      girls) participated in all five tests, of which 69 (26%) children reported to
      have a migration background (MB). Mixed-model ANOVA did not reveal a
      significantly different development of physical fitness (according to the mean
      total Z-score of DMT 6-18) over time, P = 0.883, partial n2  < 0.01. However,
      children with MB showed significantly lower physical fitness compared to children
      without MB, P < 0.001, partial n2  = 0.06. Controlling for BMI and age did not
      alter the interpretation of the results. Analyses of the single test items
      revealed significant differences in motor tests involving strength and endurance.
      CONCLUSION: Primary school children with and without MB significantly increased
      their physical fitness over time in a comparable manner. However, children with
      MB showed a significantly lower physical fitness at all test time points, which
      was only partly explained by a higher mean BMI in children with MB. Children with
      MB outreached the mean baseline fitness level of children without MB not until
      the fourth test time point, that is after two years. Therefore, a special focus
      on physical fitness particularly including strength and endurance capacities
      should be directed to children with MB already in young ages.

PMID- 30276867
TI  - Folding 2D Structures into 3D Configurations at the Micro/Nanoscale: Principles,
      Techniques, and Applications.
AB  - Compared to their 2D counterparts, 3D micro/nanostructures show larger degrees of
      freedom and richer functionalities; thus, they have attracted increasing
      attention in the past decades. Moreover, extensive applications of 3D
      micro/nanostructures are demonstrated in the fields of mechanics, biomedicine,
      optics, etc., with great advantages. However, the mainstream
      micro/nanofabrication technologies are planar ones; therefore, they cannot be
      used directly for the construction of 3D micro/nanostructures, making 3D
      fabrication at the micro/nanoscale a great challenge. A promising strategy to
      overcome this is to combine the state-of-the-art planar fabrication techniques
      with the folding method to produce 3D structures. In this strategy, 2D components
      can be easily produced by traditional planar techniques, and then, 3D structures
      are constructed by folding each 2D component to specific orientations. In this
      way, not only will the advantages of existing planar techniques, such as high
      precision, programmable patterning, and mass production, be preserved, but the
      fabrication capability will also be greatly expanded without complex and
      expensive equipment modification/development. The goal here is to highlight the
      recent progress of the folding method from the perspective of principles,
      techniques, and applications, as well as to discuss the existing challenges and
      future prospectives.

PMID- 30276868
TI  - Molecular-targeted therapy in advanced renal cell carcinoma based on
      pharmacokinetics, pharmacodynamics and pharmacogenetics: A proposed strategy.
AB  - In advanced renal cell carcinoma, a transition of drug therapies from cytokines
      to molecular-targeted drugs and immune-oncology drugs provides more clinical
      benefits to patients, while adequate management is required for various and
      sometimes serious adverse events. At present, the relationship between the
      pharmacokinetics of many drugs and their effectiveness or adverse events has been
      elucidated, and therapeutic drug monitoring is being applied to some
      immunosuppressive, anti-epileptic and antibacterial drugs in daily clinical
      practice. Most of the molecular-targeted drugs used in patients with renal cell
      carcinoma are orally active, and are affected by absorption and disposition,
      which can be different for each individual. The monitoring of the circulating
      drug concentration could be beneficial to patients by providing information for
      the adjustment of drug dose and the maintenance of a therapeutic plasma
      concentration range. Genetic polymorphisms are known to be involved in
      pharmacokinetics, and cause individual differences in clinical efficacy and
      adverse events. Therefore, a more scientific strategy should be used in regard to
      the treatment of patients with advanced renal cell carcinoma treated with
      molecular-targeted drugs by accumulating evidence on pharmacodynamics and
      pharmacogenetics.

PMID- 30276869
TI  - Highlights and recent developments in food and drug allergy, and anaphylaxis in
      EAACI Journals (2017).
AB  - This review highlights research advances and important achievements in food
      allergy, anaphylaxis, and drug allergy that were published in the Journals of the
      European Academy of Allergy and Clinical Immunology (EAACI) in 2017. Food allergy
      and anaphylaxis research have continued to rapidly accelerate, with increasing
      numbers of outstanding developments in 2017. We saw new studies on the
      mechanisms, diagnosis, prevention of food allergy, and novel food allergens. Drug
      hypersensitivity, as well as hereditary angioedema, has been highlighted in the
      present review as the focus of recent developments. The EAACI owns three
      journals: Allergy, Pediatric Allergy and Immunology (PAI), and Clinical and
      Translational Allergy (CTA). One of the major goals of the EAACI is to support
      health promotion in which prevention of allergy and asthma plays a critical role
      and to disseminate the knowledge of allergy to all stakeholders including the
      EAACI junior members. This paper summarizes the achievements of 2017 in
      anaphylaxis, and food and drug allergy.

PMID- 30276870
TI  - De novo donor-specific HLA antibodies in heart transplantation: Do transient de
      novo DSA confer the same risk as persistent de novo DSA?
AB  - BACKGROUND: It is estimated that 25%-35% of heart transplant recipients develop
      de novo donor-specific antibodies (dnDSA). One factor that appears to play a role
      in clinical outcomes is DSA persistence. The objective of this study was to
      determine the incidence of transient and persistent dnDSA in a Canadian heart
      transplant population and to evaluate their impact on coronary allograft
      vasculopathy (CAV), graft function, and mortality. METHODS: A retrospective study
      of consecutive adult and transitioned pediatric heart transplant recipients (2008
      2015) in Toronto was performed. Clinical demographics were collected
      prospectively. HLA antibody testing was performed using Luminex single antigen
      assays. In statistical analysis, dnDSA was modeled as a time dependent covariate.
      RESULTS: During a median follow-up of 4.1 years, dnDSA were detected in 42 (23%)
      with a median time to detection of 329 days (156-740); 27 (64%) developed
      persistent dnDSA. Persistent dnDSA conferred an increased risk of death with a HR
      4.0 (95%CI 1.4-12.1) when adjusted recipient age, CAV, and cytomegalovirus
      status. CONCLUSIONS: Transient dnDSA were not associated with adverse outcomes
      after heart transplantation. This suggests that transient dnDSA may not require
      enhanced immunosuppression, increased HLA antibody monitoring, or additional
      physiological assessment. By knowing the transient dnDSA status, clinicians may
      minimize both recipient morbidity and cost without increasing harm.

PMID- 30276871
TI  - Fabrication of Single-Atom Catalysts with Precise Structure and High Metal
      Loading.
AB  - In recent years, single-atom catalysts (SACs) have attracted particular interest
      and have been demonstrated to be a promising material in energy conversion and
      chemical transformation due to their optimal atom utilization and unique size
      quantum effect. The development of a versatile and simple synthetic approach for
      SACs is important for further investigation of their properties. In this regard,
      several physical and chemical methods have been developed to access SACs by
      varying the interaction between metal centers and the coordination defects of the
      supports. The common challenges for SACs in industrial applications are accurate
      control over the local structure of single sites and increasing the active-site
      density. On one hand, the rational design of the atomic structure is decisive to
      their intrinsic activity, which will affect the adsorption and activation of
      reactants over the single sites. On the other hand, increasing the metal loading
      of SACs would largely enhance the density of active sites and the corresponding
      mass activity, especially for industrial applications. Here, approaches to the
      synthesis of SACs-focusing on these two challenges-are highlighted.

PMID- 30276872
TI  - Longitudinal associations of physical activity and sedentary time with
      cardiometabolic risk factors in children.
AB  - BACKGROUND: There are few prospective studies on the associations of changes in
      objectively measured vigorous physical activity (VPA? ), moderate-to-vigorous
      physical activity (MVPA? ), light physical activity (LPA? ), and sedentary time
      (ST? ) with changes in cardiometabolic risk factors (? ) in children. We
      therefore investigated these relationships among children. METHODS: The
      participants were a population sample of 258 children aged 6-8 years followed for
      2 years. We assessed PA and ST by a combined heart rate and movement sensor;
      computed continuous age- and sex-adjusted z-scores for waist circumference, blood
      pressure, and fasting insulin, glucose, triglycerides, and high-density
      lipoprotein (HDL) cholesterol; and constructed a cardiometabolic risk score (CRS)
      of these risk factors. Data were analyzed using linear regression models adjusted
      for age, sex, the explanatory and outcome variables at baseline, and puberty.
      RESULTS: VPA? associated inversely with CRS? (beta = -0.209, P = 0.001), body fat
      percentage (BF%)? (beta = -0.244, P = 0.001), insulin? (beta = -0.220, P =
      0.001), and triglycerides? (beta = -0.164, P = 0.012) and directly with HDL
      cholesterol? (beta = 0.159, P = 0.023). MVPA? associated inversely with CRS?
      (beta = -0.178, P = 0.012), BF%? (beta = -0.298, P = <0.001), and insulin? (beta
      = -0.213, P = 0.006) and directly with HDL cholesterol? (beta = 0.184, P =
      0.022). LPA? only associated negatively with CRS? (beta = -0.163, P = 0.032). ST?
      associated directly with CRS? (beta = 0.218, P = 0.003), BF%? (beta = 0.212, P =
      0.016), and insulin? (beta = 0.159, P = 0.049). CONCLUSIONS: Increased VPA and
      MVPA and decreased ST were associated with reduced overall cardiometabolic risk
      and major individual risk factors. Change in LPA had weaker associations with
      changes in these cardiometabolic risk factors. Our findings suggest that
      increasing at least moderate-intensity PA and decreasing ST decrease
      cardiometabolic risk in children.

PMID- 30276873
TI  - Light-Activated Nanoprobes for Biosensing and Imaging.
AB  - Fluorescent nanoprobes are indispensable tools to monitor and analyze biological
      species and dynamic biochemical processes in cells and living bodies.
      Conventional nanoprobes have limitations in obtaining imaging signals with high
      precision and resolution because of the interference with biological
      autofluorescence, off-target effects, and lack of spatiotemporal control. As a
      newly developed paradigm, light-activated nanoprobes, whose imaging and sensing
      activity can be remotely regulated with light irradiation, show good potential to
      overcome these limitations. Herein, recent research progress on the design and
      construction of light-activated nanoprobes to improve bioimaging and sensing
      performance in complex biological systems is introduced. First, recent innovative
      strategies and their underlying mechanisms for light-controlled imaging are
      reviewed, including photoswitchable nanoprobes and phototargeted nanosystems.
      Subsequently, a short highlight is provided on the development of light
      activatable nanoprobes for biosensing, which offer possibilities for the remote
      control of biorecognition and sensing activity in a precise manner both
      temporally and spatially. Finally, perspectives and challenges in light-activated
      nanoprobes are commented.

PMID- 30276874
TI  - Evaluating the role of tissue microRNA-27b as a diagnostic marker for oral lichen
      planus and possible correlation with CD8.
AB  - BACKGROUND: MicroRNA-27b (miR27b) is a small, non-coding RNA that is involved in
      physiological keratinocyte differentiation and regulating inflammatory processes.
      We performed this study to investigate the value of miR27b as a diagnostic marker
      for oral lichen planus (OLP) and the correlation between CD8 (cytotoxic T-cell
      marker) and miR27b tissue expression in OLP patients. METHODS: Forty participants
      (including 20 OLP patients and 20 controls) underwent oral biopsy. The obtained
      specimens were examined by immunostaining and quantitative RT-PCR for CD8 and
      miR27b tissue expression, respectively. We used the Spearman rank correlation
      test to evaluate the correlation between both variables. RESULTS: Our analysis
      showed that in comparison with healthy tissues, OLP tissue samples exhibited
      significantly higher CD8 levels (P < 0.01), as well as a significant
      downregulation of miR27b expression (P < 0.0001). Upon comparing different OLP
      subgroups, no significant difference was detected in terms of miR27b expression;
      however, the tissue levels of CD8 varied significantly (highest in the erosive
      subgroup and lowest in the papular/plaque/reticular subgroup). The Spearman rank
      analysis showed a negative correlation between tissue expression of miR27b and
      CD8; however, this was not statistically significant (P > 0.05). Further, the
      receiver operating characteristic curve of tissue miR27b as an OLP biomarker
      revealed 100% sensitivity and 65% specificity at cutoff value of 4.4. CONCLUSION:
      This study demonstrated increased CD8 levels and downregulation of miR27b in OLP
      tissues, compared to healthy tissues. Moreover, it revealed the potential of
      miR27b as an OLP disease biomarker. The possible negative correlation between CD8
      and miR27b tissue expression requires further investigation in larger studies.

PMID- 30276875
TI  - Vascular depression and the death of Queen Victoria.
AB  - OBJECTIVES: The aim of this article was to examine relationships between the
      neurological events that were the immediate cause of the death of Queen Victoria
      and the late-life depression that preceded it. METHODS/DESIGN: The authors
      closely reviewed the surviving medical notes of Queen Victoria's personal
      physician, Sir James Reid,Bt. recorded during the Queen's last 10 days of life.
      These notes were summarized in a chronological narrative and their implications
      considered in light of current concepts of vascular depression. RESULTS: The
      depression that Queen Victoria experienced over the 5 months prior to her death
      and during her final 10 days from 13 January 1901 until 22 January likely had a
      vascular etiology. CONCLUSIONS: Although conclusions from this study are
      necessarily speculative given the lack of neuroimaging and other diagnostic tools
      available in 1901, it emerged that Queen Victoria had experienced early-onset
      depression followed in later life by an acute depressive episode associated with
      vascular risk factors and personal losses, a sequence also encountered by today's
      geriatricians. In addition, etiological connections between the Queen's early
      onset and late-life depressions appeared probable. Underlined for contemporary
      practitioners are the suffering experienced by patients with vascular depression
      at the end of their lives, as well as the struggles of physicians like Sir James
      Reid to provide clinical wisdom and emotional support.

PMID- 30276876
TI  - Erratum.

PMID- 30276878
TI  - Surface Effect on 2D Hybrid Perovskite Crystals: Perovskites Using an
      Ethanolamine Organic Layer as an Example.
AB  - Despite the remarkable progress of optoelectronic devices based on hybrid
      perovskites, there are significant drawbacks, which have largely hindered their
      development as an alternative of silicon. For instance, hybrid perovskites are
      well-known to suffer from moisture instability which leads to surface
      degradation. Nonetheless, the dependence of the surface effect on the moisture
      stability and optoelectronic properties of hybrid perovskites has not been fully
      investigated. In this work, the influence of the surface effect of 2D layered
      perovskites before and after mechanical exfoliation, representing rough and
      smooth surfaces of perovskite crystals, are studied. It is found that the smooth
      2D perovskite is less sensitive to ambient moisture and exhibits a considerably
      low dark current, which outperforms the rough perovskites by 23.6 times in terms
      of photodetectivity. The superior moisture stability of the smooth perovskites
      over the rough perovskites is demonstrated. Additionally, ethanolamine is
      employed as an organic linker of the 2D layered perovskite, which further
      improves the moisture stability. This work reveals the strong dependence of the
      surface conditions of 2D hybrid perovskite crystals on their moisture stability
      and optoelectronic properties, which are of utmost importance to the design of
      practical optoelectronic devices based on hybrid perovskite crystals.

PMID- 30276879
TI  - In Situ Li3 PS4 Solid-State Electrolyte Protection Layers for Superior Long-Life
      and High-Rate Lithium-Metal Anodes.
AB  - A thin and adjustable Li3 PS4 (LPS) solid-state electrolyte protection layer on
      the surface of Li is proposed to address the dynamic plating/stripping process of
      Li metal. The LPS interlayer is formed by an in situ and self-limiting reaction
      between P4 S16 and Li in N-methyl-2-pyrrolidone. By increasing the concentration
      of P4 S16 , the thickness of the LPS layer can be adjusted up to 60 nm. Due to
      the high ionic conductivity and low electrochemical activity of Li3 PS4 , the
      intimate protection layer of LPS can not only prevent the formation of Li
      dendrites, but also reduces parasitic side reactions and improves the
      electrochemical performance. As a result, symmetric cells with the LPS protection
      layer can deliver stable Li plating/stripping for 2000 h. Full cells assembled
      with the LPS-protected Li exhibit two times higher capacity retention in Li-S
      batteries (~800 mAh g-1 ) at 5 A g-1 for over 400 cycles compared to their bare
      Li counterparts. Furthermore, high rate performances can be achieved with Li
      LPS/LiCoO2 cells, which are capable of cycling at rates as high as 20 C. This
      innovative and scalable approach to stabilizing the Li anode can serve as a basis
      for the development of next-generation high-performance lithium-metal batteries.

PMID- 30276880
TI  - Nanoparticle-Conjugate TLR7/8 Agonist Localized Immunotherapy Provokes Safe
      Antitumoral Responses.
AB  - Localized therapeutic modalities that subvert the tumor microenvironment from
      immune-suppressive to pro-immunogenic can elicit systemic antitumor immune
      responses that induce regression of directly treated as well as nontreated distal
      tumors. A key toward generating robust antitumor T cell responses is the
      activation of dendritic cells (DCs) in the tumor microenvironment. Treatment with
      agonists triggering various pattern recognition receptors is very efficient to
      activate DCs, yet suffers from the induction of serious immune-related adverse
      effects, which is closely linked to their unfavorable PK/PD profile causing
      systemic immune activation and cytokine release. Here, it is reported that
      nanoparticle conjugation of a highly potent TLR7/8 agonist restricts immune
      activation to the tumor bed and its sentinel lymph nodes without hampering
      therapeutic antitumor efficacy. On a mechanistic level, it is confirmed that
      localized treatment with a nanoparticle-conjugated TLR7/8 agonist leads to potent
      activation of DCs in the sentinel lymph nodes and promotes proliferation of tumor
      antigen-specific CD8 T cells. Furthermore, therapeutic improvement upon
      combination with anti-PDL1 checkpoint inhibition and Flt3L, a growth factor that
      expands and mobilizes DCs from the bone marrow, is demonstrated. The findings
      provide a rational base for localized tumor engineering by nanomedicine
      strategies that provide spatial control over immune-activation.

PMID- 30276881
TI  - Near-Infrared Ternary Tandem Solar Cells.
AB  - The paucity of near-infrared (NIR) organic materials with high absorption at long
      wavelengths, combined with large diffusion lengths and charge mobilities, is an
      impediment to progress in achieving high-efficiency organic tandem solar cells.
      Here a subcell is employed within a series tandem stack that comprises a solution
      processed ternary blend of two NIR-absorbing nonfullerene acceptors and a polymer
      donor combined with a small-molecular-weight, short-wavelength fullerene-based
      subcell grown by vacuum thermal evaporation. The ternary cell achieves a power
      conversion efficiency of 12.6 +/- 0.3% with a short-circuit current of 25.5 +/-
      0.3 mA cm-2 , an open-circuit voltage of 0.69 +/- 0.01 V, and a fill factor of
      0.71 +/- 0.01 under 1 sun, AM 1.5G spectral illumination. The success of this
      device is a result of the nearly identical offset energies between the lowest
      unoccupied molecular orbitals (LUMOs) of the donors with the highest occupied
      molecular orbital (HOMO) of the acceptor, resulting in a high open-circuit
      voltage. A tandem structure with an antireflection coating combining these
      subcells demonstrates a power conversion efficiency of 15.4 +/- 0.3%.

PMID- 30276882
TI  - "Unleaded" Perovskites: Status Quo and Future Prospects of Tin-Based Perovskite
      Solar Cells.
AB  - The tremendous interest focused on organic-inorganic halide perovskites since
      2012 derives from their unique optical and electrical properties, which make them
      excellent photovoltaic materials. Pb-based halide perovskite solar cells, in
      particular, currently stand at a record efficiency of ~23%, fulfilling their
      potential toward commercialization. However, because of the toxicity concerns of
      Pb-based perovskite solar cells, their market prospects are hindered. In
      principle, Pb can be replaced with other less-toxic, environmentally benign
      metals. Sn-based perovskites are thus the far most promising alternative due to
      their very similar and perhaps even superior semiconductor characteristics. After
      years of effort invested in Sn-based halide perovskites, sufficient breakthroughs
      have finally been achieved that make them the next runners up to the Pb halide
      perovskites. To help the reader better understand the nature of Sn-based halide
      perovskites, their optical and electrical properties are systematically
      discussed. Recent progress in Sn-based perovskite solar cells, focusing mainly on
      film fabrication methods and different device architectures, and highlighting
      roadblocks to progress and opportunities for future work are reviewed. Finally, a
      brief overview of mixed Sn/Pb-based systems with their anomalous yet beneficial
      optical trends are discussed. The current challenges and a future outlook for Sn
      based perovskites are discussed.

PMID- 30276883
TI  - Molybdenum Carbide Nanodots Enable Efficient Electrocatalytic Nitrogen Fixation
      under Ambient Conditions.
AB  - Electrocatalytic nitrogen fixation is considered a promising approach to achieve
      NH3 production. However, due to the chemical inertness of nitrogen, it is
      necessary to develop efficient catalysts to facilitate the process of nitrogen
      reduction. Here, molybdenum carbide nanodots embedded in ultrathin carbon
      nanosheets (Mo2 C/C) are developed to serve as a catalyst candidate for highly
      efficient and robust N2 fixation through an electrocatalytic nitrogen reduction
      reaction (NRR). The as-synthesized Mo2 C/C nanosheets show excellent catalytic
      performance with a high NH3 yield rate (11.3 ug h-1 mg-1 Mo2C ) and Faradic
      efficiency (7.8%) for NRR under ambient conditions. More importantly, the
      isotopic experiments using 15 N2 as a nitrogen source confirm that the
      synthesized ammonia is derived from the direct supply of nitrogen. This result
      also demonstrates the possibility of high-efficiency nitrogen reduction even
      though accompanied with vigorous hydrogen evolution.

PMID- 30276884
TI  - Examining differences in neuropsychiatric symptom factor trajectories in
      empirically derived mild cognitive impairment subtypes.
AB  - OBJECTIVE: The aim of this study was to examine neuropsychiatric symptom (NPS)
      factor severity progression over time in empirically derived (ED) mild cognitive
      impairment (MCI) subtypes. METHODS: Participants in the Alzheimer's Disease
      Neuroimaging Initiative study diagnosed with MCI by Alzheimer's Disease
      Neuroimaging Initiative protocol using conventional clinical (CC) criteria (n =
      788) were reclassified using cluster analysis as amnestic, dysnomic, dysexecutive
      MCI, or cluster-derived normal (CC-Normal) using empirical criteria. Cognitively
      normal (CN) participants (n = 207) were also identified. The Neuropsychiatric
      Inventory-Questionnaire (NPI-Q) was administered from baseline through 48-month
      follow-up. Exploratory factor analysis was completed to determine the NPI-Q
      factor structure at 6-month follow-up. Multilevel modeling was used to determine
      NPI-Q symptom severity factor and apathy symptom progression over time by
      cognitive subtype. RESULTS: The exploratory factor analysis revealed that the NPI
      Q consisted of 2 factors: hyperactivity/agitation and mood symptoms. Using
      clinical and empirical criteria, all MCI groups were identified as having more
      severe hyperactivity/agitation symptoms than CN participants. However, only the
      amnestic MCI group identified using empirical criteria showed an increase in
      symptom severity over time relative to CN participants. Mood factor and apathy
      symptoms were found to be more severe in dysexecutive and amnestic groups in both
      models. Similarly, both models identified a significant worsening of mood and
      apathy symptoms over time for dysexecutive and amnestic groups relative to CN
      participants. CONCLUSIONS: This study provides further support that empirical
      criteria aid in examining the progression of clinical characteristics associated
      with MCI. Further, it helps to identify which MCI subtypes may be at higher risk
      for NPS progression.

PMID- 30276885
TI  - Butylamine-Catalyzed Synthesis of Nanocrystal Inks Enables Efficient Infrared CQD
      Solar Cells.
AB  - The best-performing colloidal-quantum-dot (CQD) photovoltaic devices suffer from
      charge recombination within the quasi-neutral region near the back hole
      extracting junction. Graded architectures, which provide a widened depletion
      region at the back junction of device, could overcome this challenge. However,
      since today's best materials are processed using solvents that lack
      orthogonality, these architectures have not yet been implemented using the best
      performing CQD solids. Here, a new CQD ink that is stable in nonpolar solvents is
      developed via a neutral donor ligand that functions as a phase-transfer catalyst.
      This enables the realization of an efficient graded architecture that, with an
      engineered band-alignment at the back junction, improves the built-in field and
      charge extraction. As a result, optimized IR CQD solar cells (Eg ~ 1.3 eV)
      exhibiting a power conversion efficiency (PCE) of 12.3% are reported. The
      strategy is applied to small-bandgap (1 eV) IR CQDs to augment the performance of
      perovskite and crystalline silicon (cSi) 4-terminal tandem solar cells. The
      devices show the highest PCE addition achieved using a solution-processed active
      layer: a value of +5% when illuminated through a 1.58 eV bandgap perovskite front
      filter, providing a pathway to exceed PCEs of 23% in 4T tandem configurations
      with IR CQD PVs.

PMID- 30276886
TI  - Graphene/Organic Semiconductor Heterojunction Phototransistors with Broadband and
      Bi-directional Photoresponse.
AB  - A graphene-semiconductor heterojunction is very attractive for realizing highly
      sensitive phototransistors due to the strong absorption of the semiconductor
      layer and the fast charge transport in the graphene. However, the photoresponse
      is usually limited to a narrow spectral range determined by the bandgap of the
      semiconductor. Here, an organic heterojunction (C60 /pentacene) is incorporated
      on graphene to realize a broadband (405-1550 nm) phototransistor with a high gain
      of 5.2 * 105 and a response time down to 275 us. The visible and near-infrared
      parts of the photoresponsivity (9127 A W-1 @650 nm and 1800 A W-1 @808 nm) come
      from the absorption of the organic layer and the graphene, respectively. For the
      first time, a bi-directional (positive and negative) photoresponse is
      demonstrated at different wavelengths, due to the opposite charge transfer
      direction of the photoexcited carriers enforced by the unique band alignment.
      Such tunability will enable new functionalities such as large-scale real-time
      optical image and infrared focal plane array detection in the future.

PMID- 30276887
TI  - Efficient Nonfullerene Organic Solar Cells with Small Driving Forces for Both
      Hole and Electron Transfer.
AB  - State-of-the-art organic solar cells (OSCs) typically suffer from large voltage
      loss (Vloss ) compared to their inorganic and perovskite counterparts. There are
      some successful attempts to reduce the Vloss by decreasing the energy offsets
      between the donor and acceptor materials, and the OSC community has demonstrated
      efficient systems with either small highest occupied molecular orbital (HOMO)
      offset or negligible lowest unoccupied molecular orbital (LUMO) offset between
      donors and acceptors. However, efficient OSCs based on a donor/acceptor system
      with both small HOMO and LUMO offsets have not been demonstrated simultaneously.
      In this work, an efficient nonfullerene OSC is reported based on a donor polymer
      named PffBT2T-TT and a small-molecular acceptor (O-IDTBR), which have identical
      bandgaps and close energy levels. The Fourier-transform photocurrent spectroscopy
      external quantum efficiency (FTPS-EQE) spectrum of the blend overlaps with those
      of neat PffBT2T-TT and O-IDTBR, indicating the small driving forces for both hole
      and electron transfer. Meanwhile, the OSCs exhibit a high electroluminescence
      quantum efficiency (EQEEL ) of ~1 * 10-4 , which leads to a significantly
      minimized nonradiative Vloss of 0.24 V. Despite the small driving forces and a
      low Vloss , a maximum EQE of 67% and a high power conversion efficiency of 10.4%
      can still be achieved.

PMID- 30276888
TI  - Ultrasmall Metal Nanoparticles Confined within Crystalline Nanoporous Materials:
      A Fascinating Class of Nanocatalysts.
AB  - Crystalline nanoporous materials with uniform porous structures, such as zeolites
      and metal-organic frameworks (MOFs), have proven to be ideal supports to
      encapsulate ultrasmall metal nanoparticles (MNPs) inside their void nanospaces to
      generate high-efficiency nanocatalysts. The nanopore-encaged metal catalysts
      exhibit superior catalytic performance as well as high stability and catalytic
      shape selectivity endowed by the nanoporous matrix. In addition, the synergistic
      effect of confined MNPs and nanoporous frameworks with active sites can further
      promote the catalytic activities of the composite catalysts. Herein, recent
      progress in nanopore-encaged metal nanocatalysts is reviewed, with a special
      focus on advances in synthetic strategies for ultrasmall MNPs (<5 nm), clusters,
      and even single atoms confined within zeolites and MOFs for various heterogeneous
      catalytic reactions. In addition, some advanced characterization methods to
      elucidate the atomic-scale structures of the nanocatalysts are presented, and the
      current limitations of and future opportunities for these fantastic nanocatalysts
      are also highlighted and discussed. The aim is to provide some guidance for the
      rational synthesis of nanopore-encaged metal catalysts and to inspire their
      further applications to meet the emerging demands in catalytic fields.

PMID- 30276889
TI  - Fluorinated Carbohydrates as Lectin Ligands: Synthesis of OH/F-Substituted N
      Glycan Core Trimannoside and Epitope Mapping by 2D STD-TOCSYreF NMR spectroscopy.
AB  - Glycan-protein interactions play an important role in a broad range of
      physiological processes, raising interest to elucidate the structural interplay.
      Yet, their dynamic nature limits the analysis by crystallography, whereas NMR
      spectroscopy suffers from the low 1 H dispersion of glycans. Therefore, their
      sparse fluorination and NMR screening by 1D Saturation Transfer Difference with
      relay to 19 F (STDreF) was previously proposed to exploit the superior dispersion
      in 19 F NMR spectroscopy. A new 2D STD-TOCSYreF experiment is presented here that
      enables comprehensive epitope mapping of fluorinated glycans by combining the
      spectral resolution of 19 F with the spatial resolution and coverage of 1 H. For
      an illustration, the 2-deoxy-2-fluoro derivative of the N-glycan core
      trimannoside was synthesised and its recognition of Pisum sativum agglutinin by
      either of the two terminal mannose residues was confirmed. Going beyond the
      crystallographic information, the 2D STD-TOCSYreF spectrum moreover visualised
      collateral contacts from the branching mannose and allowed to assess the ratio of
      both co-existing binding modes through the alpha1,3- (67 %) and alpha1,6-linked
      (33 %) terminal mannose moieties.

PMID- 30276890
TI  - Role of NMDA and AMPA glutamatergic receptors in the effects of social defeat on
      the rewarding properties of MDMA in mice.
AB  - Exposure to social stress alters the response to drugs of abuse of experimental
      animals. Changes in the glutamatergic system seem to play a role in the effects
      of social defeat stress on the rewarding properties of cocaine and amphetamine.
      The aim of the present study was to evaluate the involvement of N-methyl-D
      aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA) glutamate receptors in the effects of social defeat on the conditioned
      place preference induced by 3,4-methylenedioxymethamphetamine (MDMA). Our
      hypothesis was that changes in these receptors could mediate the effects of
      social defeat on MDMA reward. Young adult male mice were exposed to an episode of
      social defeat with an aggressive conspecific immediately before each conditioning
      session with MDMA (1.25 mg/kg, four sessions on alternating days). According to
      the treatment received before defeats, six groups were used: saline, 5 or 10
      mg/kg of memantine (NMDA antagonist) and 0.25, 1 or 5 mg/kg of 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) (AMPA antagonist). One control group was
      exposed to exploration before place conditioning. In two additional defeated and
      control groups, the membrane expression of NMDA and AMPA receptors was determined
      in the striatum and the hippocampus. Control and memantine-treated groups
      developed place preference, but not defeated mice treated with saline or CNQX,
      suggesting that the blockade of NMDA receptors reversed the effects of social
      defeat. Social defeat decreased the expression of several subunits of NMDA and
      AMPA receptors, mainly GluN1 and GluA1. These results demonstrated that
      glutamatergic plasticity is involved in the effects of social defeat stress on
      MDMA reward.

PMID- 30276892
TI  - Editorial Comment to Testicular adrenal rest tumor without congenital adrenal
      hyperplasia: A rare case.

PMID- 30276893
TI  - The small protein MgtS and small RNA MgrR modulate the PitA phosphate symporter
      to boost intracellular magnesium levels.
AB  - In response to low levels of magnesium (Mg2+ ), the PhoQP two component system
      induces the transcription of two convergent genes, one encoding a 31-amino acid
      protein denoted MgtS and the second encoding a small, regulatory RNA (sRNA)
      denoted MgrR. Previous studies showed that the MgtS protein interacts with and
      stabilizes the MgtA Mg2+ importer to increase intracellular Mg2+ levels, while
      the MgrR sRNA base pairs with the eptB mRNA thus affecting lipopolysaccharide
      modification. Surprisingly, we found overexpression of the MgtS protein also
      leads to induction of the PhoRB regulon. Studies to understand this activation
      showed that MgtS forms a complex with a second protein, PitA, a cation-phosphate
      symporter. Given that the additive effect of ?mgtA and ?mgtS mutations on
      intracellular Mg2+ concentrations seen previously is lost in the ?pitA mutant, we
      suggest that MgtS binds to and prevents Mg2+ leakage through PitA under Mg2+ 
      limiting conditions. Consistent with a detrimental role of PitA in low Mg2+ , we
      also observe MgrR sRNA repression of PitA synthesis. Thus, PhoQP induces the
      expression of two convergent small genes in response to Mg2+ limitation whose
      products act to modulate PitA at different levels to increase intracellular Mg2+
      .

PMID- 30276894
TI  - Selective Targeting of the Zinc Finger Domain of HIV Nucleocapsid Protein NCp7
      with Ruthenium Complexes.
AB  - Nucleocapsid protein 7 (NCp7) is an attractive target for anti-HIV drug
      development. Here we found that ruthenium complexes are reactive to NCp7 and
      various Ru-agents exhibit significantly different reactivity. Interestingly, the
      zinc-finger domains of NCp7 also demonstrate different affinity to Ru-complexes;
      the C-terminal domain is much more reactive than the N-terminal domain. Each zinc
      finger domain of NCp7 binds up to three Ru-motifs, and the ruthenium binding
      causes zinc-ejection from NCp7 and disrupts the protein folding. Therefore,
      ruthenium complexes interfere with the DNA binding of NCp7 and interrupt the
      protein function. The different reactivity of Ru-agents suggests a feasible
      strategy for improving the targeting of NCp7 by ligand design. This work provides
      an insight into the mechanism of ruthenium complex with NCp7, and suggests more
      potential application of ruthenium drugs.

PMID- 30276895
TI  - Orchestration of brain oscillations: principles and functions.

PMID- 30276896
TI  - Oxazoline or Oxazolinium Ion? The Protonation State and Conformation of the
      Reaction Intermediate of Chitinase Enzymes Revisited.
AB  - The enzymatic hydrolysis of chitin, one of the most abundant carbohydrates in
      nature, is achieved by chitinases, enzymes of increasing importance in
      biomedicine and industry. Unlike most retaining glycosidases, family GH18
      chitinases follow a substrate-assisted mechanism in which the 2-acetamido group
      of one N-acetylglucosamine monomer, rather than a basic residue of the enzyme,
      reacts with the sugar anomeric carbon, forming an intermediate that has been
      described as an oxazolinium ion. Based on QM/MM metadynamics simulations on
      chitinase B from Serratia marcescens, we show that the reaction intermediate of
      GH18 chitinases features instead a neutral oxazoline in a 4 C1 /4 H5
      conformation, with an oxazolinium ion being formed on the pathway towards the
      reaction products. The role of a well-defined hydrogen-bond network that operates
      around the N-acetyl group, orchestrating catalysis by protonation events, is
      discussed.

PMID- 30276897
TI  - Brain metabolism under different anesthetic conditions using hyperpolarized [1-13
      C]pyruvate and [2-13 C]pyruvate.
AB  - Carbon-13 NMR spectroscopy (13 C MRS) offers the unique capability to measure
      brain metabolic rates in vivo. Hyperpolarized 13 C reduces the time required to
      assess brain metabolism from hours to minutes when compared with conventional 13
      C MRS. This study investigates metabolism of hyperpolarized [1-13 C]pyruvate and
      [2-13 C]pyruvate in the rat brain in vivo under various anesthetics:
      pentobarbital, isoflurane, alpha-chloralose, and morphine. The apparent metabolic
      rate from pyruvate to lactate modeled using time courses obtained after injection
      of hyperpolarized [1-13 C]pyruvate was significantly greater for isoflurane than
      for all other anesthetic conditions, and significantly greater for morphine than
      for alpha-chloralose. The apparent metabolic rate from pyruvate to bicarbonate
      was significantly greater for morphine than for all other anesthetic conditions,
      and significantly lower for pentobarbital than for alpha-chloralose. Results show
      that relative TCA cycle rates determined from hyperpolarized 13 C data are
      consistent with rates previously measured using conventional 13 C MRS under
      similar anesthetic conditions, and that using morphine for sedation greatly
      improves detection of downstream metabolic products compared with other
      anesthetics.

PMID- 30276898
TI  - Programming Niche Accessibility and In Vitro Stemness with Intercellular DNA
      Reactions.
AB  - Stem cells generally exist in low abundance and tend to lose stemness in the
      absence of self-renewal signals. While extracellular-matrix-mimicking techniques
      have been developed to support stem cell proliferation, the lack of niche cells
      in these synthetic systems often hampers continuous stem cell expansion and
      maintenance of pluripotency, which are indispensable for regenerative medicine.
      Here, an intercellular DNA-reaction-programmed ESPN (expansion of stem cells with
      pairing niches) strategy is developed for 3D culture of mammary stem cells
      (MaSCs). Boolean logic operations are implemented to confer DNA-programmed
      mechanical signaling and genetically engineered morphogen signaling by niche
      cells, resulting in sustained expansion of MaSCs in vitro. The creation of stem
      cell niches improves the proliferation of pluripotent cells by four times during
      one-week culture. This method thus provides a novel approach for logical
      regulation of stemness and proliferation of stem cells for biomedicine.

PMID- 30276899
TI  - Solvent-Free Mechanochemical Preparation of Hierarchically Porous Carbon for
      Supercapacitor and Oxygen Reduction Reaction.
AB  - Hierarchically porous carbon (HPC) derived from fallen flowers was prepared by a
      green method of combining solvent-free ball milling with the safe activating
      agent potassium bicarbonate. By regulating the mass ratio of KHCO3 to biochar,
      the as-prepared HPC materials possess high specific surface areas of up to 2147.9
      m2  g-1 and abundant hierarchical pores comprised of micro-, meso-, and
      macropores. The specific capacitances of the HPC materials are able to reach
      302.7 F g-1 at a current density of 0.5 A g-1 in 6 m KOH, and the symmetric
      supercapacitor composed of two identical HPC electrodes shows good stability
      because 100 % of the specific capacitance is retained after 5000 charge/discharge
      cycles and 90.5 % of the specific capacitance remains after 12 000 cycles.
      Nitrogen self-doped HPC materials also show higher electrocatalytic activity and
      stronger methanol tolerance for the oxygen reduction reaction than that of the
      commercial Pt/C catalyst. This preparation method can be extended to the green
      conversion of other varieties of biomass waste into useful carbon materials.

PMID- 30276900
TI  - Synthesis of Bis(arylethynyl)pyrrolo[3,2-b]pyrroles and Effect of Intramolecular
      Charge Transfer on Their Photophysical Behavior.
AB  - 3,6-Bis(arylethynyl)pyrrolo[3,2-b]pyrroles were synthesized through a two-step
      procedure involving double direct alkynylation of the electron-rich core followed
      by Sonogashira coupling. In comparison with the parent tetraarylo-pyrrolo[3,2
      b]pyrroles and benzo-fused pyrrolopyrroles, these new dyes showed moderately
      redshifted absorption. Almost all derivatives showed positive fluorescence
      solvatochromism and, for the first time, red-emitting pyrrolopyrroles were
      obtained. Computational studies revealed that, in most cases, there is negligible
      change in the geometry between ground and excited states. Interestingly, there
      was a fundamental difference between pyrrolopyrroles possessing electron
      withdrawing substituents at positions 2 and 5 and their analogs lacking these
      substituents. The former dyes behaved like dipolar chromophores with the lowest
      excited state both one-photon and two-photon allowed, which corresponds to
      intramolecular charge transfer occurring along the branches perpendicular to the
      pyrrolopyrrole long axis. In compounds lacking electron-withdrawing substituents
      at positions 2 and 5, intramolecular charge transfer took place along the long
      axis of pyrrolopyrrole and consequently the one-photon transitions are not two
      photon allowed. Despite displaying quadrupolar core-to-peripheral intramolecular
      charge transfer, these derivatives showed two-photon absorption cross sections in
      the NIR1 region comparable to tetraaryl-pyrrolo[3,2-b]pyrroles lacking pi
      expansion (up to about 500 GM).

PMID- 30276901
TI  - XXXVI Annual Scientific Meeting of the British Blood Transfusion Society, 3-5
      October 2018, Brighton Centre, Brighton, UK.

PMID- 30276902
TI  - Polydrug use patterns and their impact on relapse among heroin-dependent patients
      in Shanghai, China.
AB  - AIMS: To describe the polysubstance use patterns of heroin-dependent patients and
      to understand the impact of polysubstance use patterns on relapse during the 5
      years after completing compulsory rehabilitation programmes. DESIGN: In this
      secondary analysis, the baseline data of 503 heroin-dependent patients were
      linked with their 5-year follow-up data from official records. SETTING: Four
      compulsory rehabilitation centres in Shanghai, China. PARTICIPANTS: A total of
      564 heroin-dependent patients who were discharged from Shanghai compulsory
      rehabilitation facilities in 2007 and 2008 were recruited. Among these, 503
      patients with available follow-up records were included in this analysis.
      MEASUREMENTS: The baseline measurements included the Addiction Severity Index,
      the Temperament and Character Inventory and the Medical Outcomes Study Social
      Support Scale. Relapses after discharge from the compulsory rehabilitation
      centres were extracted monthly from the official electronic record system. Latent
      class analysis was used to identify different polysubstance use patterns.
      Associations between the identified latent classes and heroin use and the factors
      related to relapse during the 5-year follow-up were analysed with the Cox
      regression model. FINDINGS: Three latent classes were identified in this cohort:
      (1) alcohol polydrug users (APU; 13.7%), (2) low polydrug users (LPU; 76.5%) and
      (3) amphetamine-type stimulant polydrug users (ASPU; 9.7%). During the 5-year
      follow-up, 298 heroin patients relapsed, and the three groups showed different
      relapse rates (ASPU 69.4 versus LPU 60.5 versus APU 44.9%, P = 0.02). The average
      durations of abstinence for the three groups differed (ASPU 31.27 +/- 3.41 months
      versus LPU 36.77 +/- 1.19 months versus APU 42.46 +/- 2.81 months, P = 0.02).
      Multivariate Cox regression analyses found that the LPU [hazard ratio (HR) =
      1.63, 1.06-2.51] and ASPU (HR = 2.10, 1.24-3.56) classes were positively
      associated with the risk of heroin relapse. CONCLUSION: Polydrug use patterns
      differ among heroin-dependent patients in compulsory rehabilitation programmes in
      China. A history of polydrug use may predict heroin relapse risk among patients
      in those compulsory rehabilitation programmes.

PMID- 30276903
TI  - Shell Cross-Linked Micelles as Nanoreactors for Enantioselective Three-Step
      Tandem Catalysis.
AB  - Functionalized amphiphilic poly(2-oxazoline)-based triblock copolymers that
      assemble into shell cross-linked micelles (SCMs) are described. These micelles
      permit the site isolation of three incompatible catalysts through
      compartmentalization, thereby enabling three-step non-orthogonal tandem processes
      in one pot. In particular, the acid-catalyzed ketal hydrolysis to prochiral
      ketones proceeded in the hydrophilic corona, followed by the Rh-catalyzed
      asymmetric transfer hydrogenation to enantio-enriched alcohols in the cross
      linked shell, and nucleophilic base-catalyzed acylation in the hydrophobic core.
      The catalysts are positioned in close proximity on a single micelle support to
      take advantage of the intramicellar substrate diffusion, yet they are
      sufficiently spaced apart from each other in physically distinct
      microenvironments. These compartmentalized micelles are substrate selective and,
      on a basic level, mimic compartmentalized catalytic architectures found in
      nature.

PMID- 30276904
TI  - Electronic and Structural Engineering of Carbon-Based Metal-Free Electrocatalysts
      for Water Splitting.
AB  - Since first being reported as possible electrocatalysts to substitute platinum
      for the oxygen reduction reaction (ORR), carbon-based metal-free nanomaterials
      have been considered a class of promising low-cost materials for clean and
      sustainable energy-conversion reactions. However, beyond the ORR, the development
      of carbon-based catalysts for other electrocatalytic reactions is still limited.
      More importantly, the intrinsic activity of most carbon-based metal-free
      catalysts is inadequate compared to their metal-based counterparts. To address
      this challenge, more design strategies are needed in order to improve the overall
      performance of carbon-based materials. Herein, using water splitting as an
      example, some state-of-the-art strategies in promoting carbon-based nanomaterials
      are summarized, including graphene, carbon nanotubes, and graphitic-carbon
      nitride, as highly active electrocatalysts for hydrogen evolution and oxygen
      evolution reactions. It is shown that by rationally tuning the electronic and/or
      physical structure of the carbon nanomaterials, adsorption of reaction
      intermediates is optimized, consequently improving the apparent electrocatalytic
      performance. These strategies may facilitate the development in this area and
      lead to the discovery of advanced carbon-based nanomaterials for various
      applications in energy-conversion processes.

PMID- 30276905
TI  - The impact of blind peer review (team reading) of equivocal/abnormal Papanicolaou
      smears on inter-reader agreement.
AB  - OBJECTIVE: Peer review of equivocal/abnormal Papanicolaou smears is a standard
      internal quality assurance measure in cervical cancer screening laboratories. In
      2014, we introduced a new method for peer review involving blinding the identity
      of the first reader. We present the comparison of different measures of inter
      reader agreement in 2013 and 2014 in order to measure the impact of blind peer
      review on possible cognitive biases in reading. METHODS: All suspect slides are
      proposed for peer review; a single reader's peer reviews are registered
      independently, with discordant cases discussed for consensus diagnosis. Since
      2014, the first reader's name has been blinded to peers. We computed how
      frequently the initial diagnosis was changed, and how frequently a single reader
      influenced the final diagnosis when the initial one was changed. We compared
      kappa of the first reader and that of other readers with final diagnosis. Data
      from 2013 were compared to those of 2014. RESULTS: The final diagnosis changed in
      22.9% of cases (range 16.8%-34.4%) in 2013 and in 26.8% (range 13.9%-35.6%) in
      2014 (P = .2). Individual peer diagnoses agreed with final diagnosis in 52.3%
      (range 41.9%-66.3%) in 2013 and in 50.2% (range 36.0%-65.8%) in 2014 (P = .55).
      The cytologist having the highest proportion of confirmed diagnoses was also the
      most influential on final diagnosis, both in 2013 and in 2014. Agreement between
      first reader and final diagnosis was higher than that of each reader in 2013 and
      in 2014. CONCLUSIONS: Blinding the identity of the first reader had little or no
      impact on inter-reader agreement measures in our laboratory.

PMID- 30276906
TI  - Age-varying effects of cannabis use frequency and disorder on symptoms of
      psychosis, depression and anxiety in adolescents and adults.
AB  - AIMS: We tested the age-varying associations of cannabis use (CU) frequency and
      disorder (CUD) with psychotic, depressive and anxiety symptoms in adolescent and
      adult samples. Moderating effects of early onset (<= 15 years) and sex were
      tested. DESIGN: Time-varying effect models were used to assess the significance
      of concurrent associations between CU and CUD and symptoms of psychosis,
      depression and anxiety at each age. SETTING AND PARTICIPANTS: Adolescent data (V
      HYS; n = 662) were collected from a randomly recruited sample of adolescents in
      Victoria, British Columbia, Canada during a 10-year period (2003-13). Adult cross
      sectional data (NESARC-III; n = 36 309) were collected from a representative
      sample from the United States (2012-13). MEASUREMENTS: Mental health symptoms
      were assessed using self-report measures of diagnostic symptoms. CU was based on
      frequency of past-year use. Past-year CUD was based on DSM-5 criteria. FINDINGS:
      For youth in the V-HYS, CU was associated with psychotic symptoms following age
      22 [b = 0.13, 95% confidence interval (CI) = 0.002, 0.25], with depressive
      symptoms from ages 16-19 and following age 25 (b = 0.17, 95% CI = 0.003, 0.34),
      but not with anxiety symptoms. CUD was associated with psychotic symptoms
      following age 23 (b = 0.51, 95% CI = 0.01, 1.01), depressive symptoms at ages 19
      20 and following age 25 (b = 0.71, 95% CI = 0.001, 1.42) and anxiety symptoms
      ages 26-27 only. For adults in the NESARC-III, CU was associated with mental
      health symptoms at most ages [e.g. psychotic symptoms; age 18 (b = 0.22, 95% CI =
      0.10, 0.33) to age 65 (b = 0.36, 95% CI = 0.16, 0.56)]. CUD was associated with
      all mental health symptoms across most ages [e.g. depressive symptoms; age 18 (b
      = 0.96, 95% CI = 0.19, 1.73) to age 61 (b = 1.11, 95% CI = 0.01, 2.21)].
      Interactions with sex show stronger associations for females than males in young
      adulthood [e.g. V-HYS: CUD * sex interaction on psychotic symptoms significant
      after age 26 (b = 1.12, 95% CI = 0.02, 2.21)]. Findings were not moderated by
      early-onset CU. CONCLUSIONS: Significant associations between cannabis use (CU)
      frequency and disorder (CUD) and psychotic and depressive symptoms in late
      adolescence and young adulthood extend across adulthood, and include anxiety.

PMID- 30276907
TI  - Impact of timing of methadone initiation on perinatal outcomes following delivery
      among pregnant women on methadone maintenance therapy in Ontario.
AB  - BACKGROUND AND AIMS: Methadone maintenance therapy (MMT) is associated with
      improved outcomes for children exposed to maternal opioid dependence in utero. We
      examined Ontario's population of pregnant women on MMT and determined the impact
      of timing of MMT initiation on perinatal outcomes. DESIGN: Cohort study. SETTING:
      Ontario, Canada. PARTICIPANTS: Women eligible for public drug benefits and on MMT
      during pregnancy between 2005 and 2015. MEASUREMENTS: We stratified women based
      on their timing of MMT initiation: (1) stabilized prior to conception, (2) newly
      initiated prior to conception, (3) initiation in trimester 1, (4) initiation in
      trimester 2 or (5) initiation in trimester 3. The primary outcomes in the
      multivariable logistic regression analysis were key perinatal health indicators:
      small for gestational age, preterm birth, congenital anomalies, severe maternal
      morbidity, caesarean section and induced labor. Secondary outcomes were specific
      to maternal opioid dependence: neonatal abstinence syndrome (NAS), admission to a
      neonatal intensive care unit (NICU), NAS treatment, removal from mother's custody
      at hospital discharge and neonatal death. FINDINGS: Among 1842 women on MMT
      during pregnancy, 87.6% (n = 1614) initiated MMT before conception. Almost a
      quarter of their infants (22.2%; n = 408) were born small for gestational age,
      17.5% (n = 323) were preterm and 5.9% (n = 109) were born with a congenital
      anomaly. The odds of primary outcomes occurring did not differ based on timing of
      methadone initiation; however, infants of mothers who initiated methadone during
      pregnancy had up to a fourfold increase in the odds of social services removal at
      the hospital [adjusted odds ratio (aOR) range = 3.70-4.19] compared with those
      whose mothers were stabilized on MMT prior to conception. CONCLUSIONS: Later
      initiation of methadone maintenance therapy among pregnant women in Ontario,
      Canada has not been found to be clearly related to most key perinatal adverse
      health outcomes.

PMID- 30276908
TI  - Assembly processes of trophic guilds in the root mycobiome of temperate forests.
AB  - Root-associated mycobiomes (RAMs) link plant and soil ecological processes,
      thereby supporting ecosystem functions. Understanding the forces that govern the
      assembly of RAMs is key to sustainable ecosystem management. Here, we dissected
      RAMs according to functional guilds and combined phylogenetic and multivariate
      analyses to distinguish and quantify the forces driving RAM assembly processes.
      Across large biogeographic scales (>1,000 km) in temperate forests (>100 plots),
      RAMs were taxonomically highly distinct but composed of a stable trophic
      structure encompassing symbiotrophic, ectomycorrhizal (55%), saprotrophic (7%),
      endotrophic (3%) and pathotrophic fungi (<1%). Taxonomic community composition of
      RAMs is explained by abiotic factors, forest management intensity, dominant tree
      family (Fagaceae, Pinaceae) and root resource traits. Local RAM assemblies are
      phylogenetically clustered, indicating stronger habitat filtering on roots in
      dry, acid soils and in conifer stands than in other forest types. The local
      assembly of ectomycorrhizal communities is driven by forest management intensity.
      At larger scales, root resource traits and soil pH shift the assembly process of
      ectomycorrhizal fungi from deterministic to neutral. Neutral or weak
      deterministic assembly processes are prevalent in saprotrophic and endophytic
      guilds. The remarkable consistency of the trophic composition of the RAMs
      suggests that temperate forests attract fungal assemblages that afford functional
      resilience under the current range of climatic and edaphic conditions. At local
      scales, the filtering processes that structure symbiotrophic assemblies can be
      influenced by forest management and tree selection, but at larger scales,
      environmental cues and host resource traits are the most prevalent forces.

PMID- 30276909
TI  - UV Light-Responsive Peptide-Based Supramolecular Hydrogel for Controlled Drug
      Delivery.
AB  - Low-molecular-weight self-assembled peptides may serve as promising hydrogelators
      for drug delivery applications by changing their structural network in response
      to external stimuli. Herein, inspired by the well-studied low-molecular-weight
      peptide hydrogelator, fluorenyl-methoxycarbonyl-diphenylalanine (Fmoc-FF), a
      novel peptide is designed and synthesized to include an ultraviolet (UV)
      sensitive phototrigger. Similar to Fmoc-FF, 6-nitroveratryloxycarbonyl
      diphenylalanine (Nvoc-FF) self-assembles to form a 3D, self-supporting,
      nanofibrous hydrogel. The Nvoc-FF hydrogel exhibits good mechanical properties
      with a storage modulus of 40 kPa. UV irradiation of the Nvoc-FF hydrogel
      encapsulating insulin-fluorescein isothiocyanate (insulin-FITC) results in the
      cleavage of Nvoc-FF peptide to produce unmasked FF, thereby facilitating the
      degradation of the hydrogel and the release of insulin-FITC. This release is in
      linear correlation to the irradiation time. In the present study, a first insight
      into this rigid, fibrous, light-responsive hydrogel is provided, allowing the
      fabrication of a novel drug delivery system for controlled release of large
      molecules.

PMID- 30276910
TI  - High intraspecific diversity of Restorer-of-fertility-like genes in barley.
AB  - Nuclear restorer of fertility (Rf) genes suppress the effects of mitochondrial
      genes causing cytoplasmic male sterility (CMS), a condition in which plants fail
      to produce viable pollen. Rf genes, many of which encode RNA-binding
      pentatricopeptide repeat (PPR) proteins, are applied in hybrid breeding to
      overcome CMS used to block self-pollination of the seed parent. Here, we
      characterise the repertoire of restorer-of-fertility-like (RFL) PPR genes in
      barley (Hordeum vulgare). We found 26 RFL genes in the reference genome ('Morex')
      and an additional 51 putative orthogroups (POGs) in a re-sequencing data set from
      262 barley genotypes and landraces. Whereas the sequences of some POGs are highly
      conserved across hundreds of barley accessions, the sequences of others are much
      more variable. High sequence variation strongly correlates with genomic location 
      the most variable genes are found in a cluster on chromosome 1H. A much higher
      likelihood of diversifying selection was found for genes within this cluster than
      for genes present as singlets. This work includes a comprehensive analysis of the
      patterns of intraspecific variation of RFL genes. The RFL sequences characterised
      in this study will be useful for the development of new markers for fertility
      restoration loci.

PMID- 30276911
TI  - Does the nicotine metabolite ratio moderate smoking cessation treatment outcomes
      in real-world settings? A prospective study.
AB  - BACKGROUND AND AIMS: In smoking treatment trials comparing varenicline with
      transdermal nicotine replacement therapy (NRT), stratified by nicotine metabolite
      (3-hydroxycotinine/cotinine) ratio (NMR), the relative benefit of varenicline is
      greater among normal rather than slow metabolizers. This study tested if the
      relative effectiveness of varenicline and NRT is associated with NMR status in a
      natural treatment setting. A secondary aim was to test if this relationship is
      moderated by behavioural support. DESIGN: Prospective observational multi-centre
      study with 4-week and 52-week follow-up. SETTING: Nine English Stop Smoking
      Services (SSS). PARTICIPANTS: Data came from 1556 smokers (aged >= 16 years)
      attending SSS between March 2012 and March 2013. INTERVENTIONS: Participants
      received pharmacotherapy together with behavioural support. MEASUREMENTS: The
      primary outcome was carbon monoxide-verified continuous abstinence at both follow
      up times. Main explanatory variables were (1) NMR status [slow (NMR < 0.31, n =
      451) versus normal (NMR >= 0.31, n = 1105) metabolizers]; (2) pharmacotherapy
      (varenicline versus NRT) and (3) behavioural support (individual versus group
      based treatment). Analyses adjusted for baseline socio-demographic, SSS,
      mental/physical health and smoking characteristics. FINDINGS: Of participants,
      44.2% [95% confidence interval (CI) = 41.7-46.6%] and 8.0% (95% CI = 6.8-9.5%)
      were continuously abstinent at 4 and 52 weeks. Varenicline was more effective
      than NRT at 4 weeks (P < 0.001) but only marginally so at 52 weeks (P = 0.061).
      There was no or inclusive evidence that NMR status moderated relative efficacy of
      varenicline and NRT at 4- [P = 0.60, Bayes factor (BF) = 0.25] or 52-week follow
      ups (P = 0.74, BF = 0.73). However, this relationship was moderated by
      behavioural support (p = 0.012): the relative benefit of varenicline over NRT at
      52-week follow-up was greater in slow, not normal, metabolizers receiving group
      rather than individual support (P = 0.012). CONCLUSIONS: In a real-world setting,
      the nicotine metabolite ratio status of treatment-seeking smokers does not appear
      to contribute substantially to the differential effectiveness of varenicline and
      nicotine replacement therapy in Stop Smoking Services, when both pharmacotherapy
      and behavioural support are self-selected.

PMID- 30276912
TI  - DNA metabarcoding unveils multiscale trophic variation in a widespread coastal
      opportunist.
AB  - A thorough understanding of ecological networks relies on comprehensive
      information on trophic relationships among species. Since unpicking the diet of
      many organisms is unattainable using traditional morphology-based approaches, the
      application of high-throughput sequencing methods represents a rapid and powerful
      way forward. Here, we assessed the application of DNA metabarcoding with nearly
      universal primers for the mitochondrial marker cytochrome c oxidase I in defining
      the trophic ecology of adult brown shrimp, Crangon crangon, in six European
      estuaries. The exact trophic role of this abundant and widespread coastal benthic
      species is somewhat controversial, while information on geographical variation
      remains scant. Results revealed a highly opportunistic behaviour. Shrimp stomach
      contents contained hundreds of taxa (>1,000 molecular operational taxonomic
      units), of which 291 were identified as distinct species, belonging to 35 phyla.
      Only twenty ascertained species had a mean relative abundance of more than 0.5%.
      Predominant species included other abundant coastal and estuarine taxa, including
      the shore crab Carcinus maenas and the amphipod Corophium volutator. Jacobs'
      selectivity index estimates based on DNA extracted from both shrimp stomachs and
      sediment samples were used to assess the shrimp's trophic niche indicating a
      generalist diet, dominated by crustaceans, polychaetes and fish. Spatial
      variation in diet composition, at regional and local scales, confirmed the highly
      flexible nature of this trophic opportunist. Furthermore, the detection of a
      prevalent, possibly endoparasitic fungus (Purpureocillium lilacinum) in the
      shrimp's stomach demonstrates the wide range of questions that can be addressed
      using metabarcoding, towards a more robust reconstruction of ecological networks.

PMID- 30276913
TI  - Phosphazene Bases as Organocatalysts for Ring-Opening Polymerization of Cyclic
      Esters.
AB  - Over the past several years, organocatalyzed polymerization reactions have
      attracted considerable attention, and these efforts have led to major advances. A
      large number of organic compounds have been proven active for the polymerization
      of a large variety of monomers. In particular, phosphazene bases (PBs) are a
      family of extremely strong, non-nucleophilic, and uncharged auxiliary bases, and
      have shown their remarkable potential as organocatalysts for the ring-opening
      polymerization (ROP) of cyclic monomers. By deprotonation of weak acids or in
      combination with lithium cation, PBs significantly enhance the nucleophilicity of
      the initiator/chain-end, thus allowing fast and usually controlled anionic
      polymerization. In this feature article, the recent advances in phosphazene
      catalyzed ROP of cyclic esters are summarized. This review is divided into three
      sections, including general features, design and synthesis, and catalytic
      applications. It aims to provide a critical analysis of PB-mediated ROP systems
      and a useful guide for the further design of organocatalysts applied to polymer
      synthesis. An outlook is given at the end.

PMID- 30276914
TI  - The relationship between socioeconomic status and white matter microstructure in
      pre-reading children: A longitudinal investigation.
AB  - Reading is a learned skill crucial for educational attainment. Children from
      families of lower socioeconomic status (SES) tend to have poorer reading
      performance and this gap widens across years of schooling. Reading relies on the
      orchestration of multiple neural systems integrated via specific white-matter
      pathways, but there is limited understanding about whether these pathways relate
      differentially to reading performance depending on SES background. Kindergarten
      white-matter FA and second-grade reading outcomes were investigated in an SES
      diverse sample of 125 children. The three left-hemisphere white-matter tracts
      most associated with reading, and their right-hemisphere homologs, were examined:
      arcuate fasciculus (AF), superior longitudinal fasciculus (SLF), and inferior
      longitudinal fasciculus (ILF). There was a significant and positive association
      between SES and fractional anisotropy (FA) in the bilateral ILF in kindergarten.
      SES moderated the association between kindergarten ILF and second grade reading
      performance, such that it was positive in lower-SES children, but not significant
      in higher-SES children. These results have implications for understanding the
      role of the environment in the development of the neural pathways that support
      reading.

PMID- 30276915
TI  - Psychosocial distress and utilization of professional psychological care in
      cancer patients: An observational study in National Comprehensive Cancer Centers
      (CCCs) in Germany.
AB  - OBJECTIVE: The study aimed to assess cancer patients' use of psychological care
      and its correlates in a large sample of cancer patients in Comprehensive Cancer
      Centers (CCCs) in Germany. METHODS: In a multicenter study in Germany, cancer
      patients with various diagnoses were evaluated for self-reported use of
      psychological support. We measured psychological distress, depression and
      anxiety, quality of life, and social support with standardized questionnaires and
      analyzed its association with the utilization of psychological care using
      multivariable logistic regression. This paper focuses on a cross-sectional
      analysis of the data assessed during inpatient care. RESULTS: Three thousand
      fifty-four (50%) of hospitalized patients were asked for participation, and n =
      1632 (53.6%) participated. We were able to analyze n = 1,398 (45.9%) patients.
      Three hundred ninety-seven (28.4%) of the sample utilized psychological support.
      Users of psychological care were significantly younger than nonusers (odds ratio
      [OR]: 0.967, P < 0.001) and were more often female (OR: 1.878, P < 0.001),
      whereas educational level was not associated with the use of psychological care.
      In the multivariable analysis, effects on the use of psychological care were
      observed for Hospital Anxiety and Depression Scale (HADS) anxiety (OR: 1.106, P =
      0.001) and both subscales of the 12-item Short Form Health Survey (SF-12) quality
      of life measure (mental, OR: 0.97, P = 0.002; physical, OR: 0.97, P = 0.002).
      CONCLUSION: Psychological distress and anxiety are higher, and quality of life is
      lower in users of psychological care in comparison with nonusers during inpatient
      cancer treatment. Although psychooncological services should be provided to all
      patients who need them, special efforts should be made to reach populations that
      report low utilization.

PMID- 30276916
TI  - Effects of high-intensity functional circuit training on motor function and sport
      motivation in healthy, inactive adults.
AB  - PURPOSE: A small share of the world's population meets current physical activity
      guidelines, which recommend regular engagement in endurance, strength, and
      neuromotor exercise. As lack of time represents a major cause of inactivity,
      multidimensional training methods with short durations may provide a promising
      alternative to classical, volume-oriented approaches focusing on one biomotor
      ability. This trial examined the effects of a high-intensity functional circuit
      training (HIFCT) on motor performance and exercise motivation in untrained
      adults. METHODS: Thirty-three inactive participants were randomly allocated to
      two groups exercising for six weeks. The intervention group (HIFCT, n = 20)
      3*/week performed functional whole-body exercises in a circuit. Each 15-minute
      workout included repetitive 20s all-out bouts with 10s breaks. In the comparison
      group (moderate aerobic exercise, MAE, n = 13), the participants walked 3*/week
      for 50 minutes at moderate intensity. Measured motor outcomes were cycling
      endurance capacity (respiratory threshold, maximum workload), maximum strength
      (leg and chest press), postural control (force plate), and jump capacity (counter
      movement jump, single leg hop for distance); exercise motivation was assessed
      using the self-concordance index. RESULTS: In comparison with MAE, HIFCT enhanced
      maximum leg strength (between-group difference of relative pre- to post-changes
      of 5.0%), shoulder strength (7.6%), and endurance workload (5.0%; P < 0.05),
      while increasing motivation to exercise (+5.5 points, P < 0.05). No between-group
      differences occurred for postural control and jump capacity (P > 0.05).
      CONCLUSION: Despite considerably shorter training duration, HIFCT enhances motor
      function and motivation to exercise more effectively than MAE. Further research
      should investigate the long-term adherence to the program and its effectiveness
      in other settings.

PMID- 30276918
TI  - SunSmart news? Traditional media coverage of sun protection issues during
      springtime in New Zealand.
AB  - ISSUES ADDRESSED: Cutaneous melanomas and keratinocyte carcinomas (nonmelanoma
      skin cancer) are highly prevalent in New Zealand (NZ), making skin cancer a
      priority area for cancer control. Spring is an important time for encouraging sun
      safety, due to ultraviolet radiation (UVR) levels becoming hazardous. The news
      media have a potential to play an important role in reminding people and
      emphasising the importance of sun-safety. This study aimed to describe how the
      traditional NZ media portrayed sun-safety and skin cancer in spring news stories.
      METHODS: A media monitoring company collated stories related to cancer during
      spring 2016. These were reviewed for inclusion and content was coded according to
      the cancer type described. Stories focused on skin cancer and sun protection
      issues were coded according to the position on the cancer control continuum.
      RESULTS: Skin cancer and sun-safety represented 3.6% (n = 110) of all cancer
      stories published. Stories mainly related to primary prevention (72%), early
      detection (37%) and survivorship (27%). The main risk factors identified included
      sun exposure (49%) and tanning (25%). CONCLUSIONS: Traditional media coverage of
      skin cancer remains relatively low during springtime. It is heartening to see
      that most stories included prevention information. SO WHAT?: Given the impact of
      skin cancer in NZ, and the importance of springtime as a period for behaviour
      change to reduce risk, there is considerable scope for increased media coverage
      and advocacy. Further research could usefully analyse media trends throughout the
      year and within specific media platforms, both traditional and new, in order to
      further disseminate information to the NZ public.

PMID- 30276917
TI  - A novel group of spindle cell tumors defined by S100 and CD34 co-expression shows
      recurrent fusions involving RAF1, BRAF, and NTRK1/2 genes.
AB  - Tumors characterized by co-expression of S100 and CD34, in the absence of SOX10,
      remain difficult to classify. Triggered by a few index cases with monomorphic
      cytomorphology and distinctive stromal and perivascular hyalinization,
      immunopositivity for S100 and CD34, and RAF1 and NTRK1 fusions, the authors
      undertook a systematic review of tumors with similar features. Most of the cases
      selected were previously diagnosed as low-grade malignant peripheral nerve sheath
      tumors, while others were deemed unclassified. The tumors were studied with
      targeted RNA sequencing and/or FISH. A total of 25 cases (15 adults and 10
      children) with kinase fusions were identified, including 8 cases involving RAF1,
      2 BRAF, 14 NTRK1, and 1 NTRK2 gene rearrangements. Most tumors showed a
      monomorphic spindle cell proliferation with stromal and perivascular keloidal
      collagen, in a patternless architecture, with only occasional scattered
      pleomorphic or multinucleated cells. Most cases showed low cellularity, a low
      mitotic count, and absence of necrosis. Although a subset showed overlap with
      lipofibromatosis-like neural tumors, the study group showed distinctive
      hyalinization and overt malignant features, such as highly cellular fascicular
      growth and primitive appearance. All tumors showed co-expression of S100 and
      CD34, ranging from focal to diffuse. SOX10 was negative in all cases. NTRK1
      immunohistochemistry showed high levels of expression in all tumors with NTRK1
      gene rearrangements. H3K27me3 expression performed in a subset of cases was
      retained. These findings together with the recurrent gene fusions in RAF1, BRAF,
      and NTRK1/2 kinases suggest a distinct molecular tumor subtype with consistent
      S100 and CD34 immunoreactivity.

PMID- 30276920
TI  - Cognitive neuroscience can support public health approaches to minimise the harm
      of 'losses disguised as wins' in multiline slot machines.
AB  - Video slot machines are associated with both accelerated transition into
      problematic forms of gambling, as well as psychosocial harm above and beyond
      other forms of gambling. A growing body of evidence is uncovering how key design
      features of multiline slot machines produce an inflated experience of reward,
      despite the fact that these features offer no overall financial benefit to the
      player. A pernicious example of this are 'losses disguised as wins' (LDWs), which
      occur when simultaneous bets placed on multiple lines result in a winning
      combination that returns an amount greater than zero, but less the total wager.
      These events are usually accompanied by the same celebratory sounds and
      animations that accompany true wins. We argue that LDWs may leverage
      neuropsychological phenomena that underlie reinforcement learning and contribute
      to extended or repetitive use and gambling-related harm. While other
      characteristics of slot machine gambling have been examined by cognitive
      neuroscientists, this feature has not yet received attention. Neuroscientific
      methods can be used to assess the impact of LDWs on the human reward system, to
      assess the claim that these events are a reinforcing and contributing factor in
      the development of harmful play. Positive findings would provide further
      persuasive evidence in support of strategies to minimise gambling harm through
      the regulation of machine design.

PMID- 30276919
TI  - Renal perfusion parameters measured by contrast-enhanced ultrasound in healthy
      dogs demonstrate a wide range of variability in the long-term.
AB  - Contrast-enhanced ultrasound may be helpful for detecting early renal
      microvascular damage and dysfunction in dogs. However, before this noninvasive
      imaging method can be tested as an early-stage screening tool in clinical
      patients, an improved understanding of long-term variation in healthy animals is
      needed. In this prospective, secondary, longitudinal, serial measurements study,
      variability of contrast-enhanced ultrasound renal perfusion parameters was
      described for eight healthy dogs, using seven time points and a period of 83
      weeks. Dogs were sedated with butorphanol (0.4 mg/kg), and contrast-enhanced
      ultrasound of each kidney was performed after an intravenous bolus injection of a
      microbubble contrast agent (0.04 mL/kg). Time-intensity curves were created from
      regions-of-interest drawn in the renal cortex and medulla. Intensity-related
      parameters representing blood volume and time-related parameters representing
      blood velocity were determined. A random-effects model using restricted maximum
      likelihood was used to estimate variance components. Within-dog coefficient of
      variation was defined as the ratio of the standard deviation over the mean. Time
      related parameters such as time-to-peak, rise and fall time had lowest within-dog
      variability. Intensity-related parameters such as peak enhancement, wash-in and
      wash-out area under the curve, total area under the curve, and wash-in and
      washout rates had high within-dog variability (coefficient of variation > 45%).
      Authors therefore recommend the use of time-related parameters for future studies
      of renal perfusion. Within-dog variability for bilateral kidney measurements was
      extremely low, therefore contrast-enhanced ultrasound may be particularly useful
      for detecting unilateral changes in renal perfusion. Future studies are needed to
      compare contrast-enhanced ultrasound findings in healthy dogs versus dogs with
      renal disease.

PMID- 30276921
TI  - Inhibitory effects of ascorbic acid toward snake venom metalloproteinase (SVMP)
      from Indian Echis carinatus venom: Insights from molecular modeling and binding
      studies.
AB  - Classical antivenom therapy is unable to shield complications of viper bite and
      has limitations such as anaphylaxis and serum sickness. Snake venom
      metalloproteinases are responsible for local tissue damage and hemorrhage at the
      bitten site in viper envenomation, and this has led to a persistent search for
      metalloproteinase inhibitors. Here, we report the inhibitory effects of ascorbic
      acid against metalloproteinase from Echis carinatus venom both in-silico and in
      vitro. Ascorbic acid effectively inhibited the proteolytic activity of E.
      carinatus venom in a dose-dependent manner. Interaction studies of ascorbic acid
      with purified ecarin using isothermal titration calorimetry showed favorable
      binding energy and energetics. The molecular docking of ascorbic acid with ecarin
      revealed important interactions with residues at the active site pocket of
      ecarin. It was observed that the ligand behaves as a chelating inhibitor. Thus,
      the backbone structural scaffold of ascorbic acid can find potential use as
      building blocks in designing drug-like molecules for viper bite management.

PMID- 30276922
TI  - Orexin-mediated restoration of hippocampal synaptic potentiation in mice with
      established cocaine-conditioned place preference.
AB  - Orexins (also called hypocretins) are implicated in reward and addiction, but
      little is known about their role(s) in the association between hippocampal
      synaptic plasticity and drug preference. Previously, we found that exogenous
      orexin via OX1 and OX2 receptors can impair low frequency stimulation-induced
      depotentiation, i.e. restoring potentiation of excitatory synaptic transmission
      (re-potentiation) in mouse hippocampal slices. Here, we found this re
      potentiation in hippocampal slices from mice that had acquired conditioned place
      preference (CPP) to cocaine. Both 10 and 20 mg/kg of cocaine induced similar
      magnitudes of CPP in mice and re-potentiation in their hippocampal slices, but
      differed in their susceptibility to TCS1102, a dual (OX1 and OX2 ) orexin
      receptor antagonist. TCS1102 significantly attenuated CPP and hippocampal re
      potentiation induced by cocaine at 10 mg/kg but not at 20 mg/kg. Nonetheless,
      SCH23390, an antagonist of dopamine D1-like receptors (D1-likeRs), inhibited the
      effects induced by both doses of cocaine. SKF38393, a D1-likeR-selective agonist,
      also induced hippocampal re-potentiation in vitro. Interestingly, this effect was
      attenuated by TCS1102. Conversely, SCH23390 prevented orexin A-induced
      hippocampal re-potentiation. These results suggest that endogenous orexins are
      released in mice during cocaine-CPP acquisition, which sustains potentiated
      hippocampal transmission via OX1 /OX2 receptors and may contribute to the
      addiction memory of cocaine. This effect of endogenous orexins, however, may be
      substituted by dopamine that may dominate hippocampal re-potentiation and CPP via
      D1-likeRs when the reinforcing effect of cocaine is high.

PMID- 30276923
TI  - A field ecologist's adventures in the virtual world: using simulations to design
      data collection for complex models.
AB  - Field data collection can be expensive, time consuming, and difficult; insightful
      research requires statistical analyses supported by sufficient data. Pilot
      studies and power analysis provide guidance on sampling design but can be
      challenging to perform, as ecologists increasingly collect multiple types of data
      over different scales. Despite a growing simulation literature, it remains
      unclear how to appropriately design data collection for many complex projects.
      Approaches that seek to achieve realism in decision-making contexts, such as
      management strategy evaluation and virtual ecologist simulations, can help. For a
      relatively complex analysis, we develop and demonstrate a flexible simulation
      approach that informs what data are needed and how long those data will take to
      collect, under realistic fieldwork constraints. We simulated data collection and
      analysis under different constraint scenarios that varied in deterministic (field
      trip length, travel, and measurement times) and stochastic (species detection and
      occupancy rates and inclement weather) features. In our case study, we fit plant
      height data to a multispecies, three-parameter, nonlinear growth model. We tested
      how the simulated data sets, based on the varying constraint scenarios, affected
      the model fit (parameter bias, uncertainty, and capture rate). Species prevalence
      in the field exerted a stronger influence on the data sets and downstream model
      performance than deterministic aspects such as travel times. When species
      detection and occupancy were not considered, the field time needed to collect an
      adequate data set was underestimated by 40%. Simulations can assist in refining
      fieldwork design, estimating field costs, and incorporating uncertainties into
      project planning. We argue that combining data collection, analysis, and decision
      making processes in a flexible virtual setting can help address many of the
      decisions that field ecologists face when designing field-based research.

PMID- 30276924
TI  - Molecular Basis for the Mechanical Response of Sulfa Drug Crystals.
AB  - Appreciating the nanomechanical response in crystalline materials demands one to
      comprehend on the elastic and plastic deformation mechanisms occurring in the
      vicinity of the nanoindenter tip, in terms of the underlying crystal structures.
      We combined the nanoindentation data with structural and computational inputs to
      derive a molecular-level understanding of the nanomechanical response in eight
      prototypical sulfa drug molecular crystals. The magnitude of the modulus, E, is
      strongly connected to the non-covalent bond features-the bond strength, the
      relative orientation with the measured crystal facet as well as their disposition
      in the crystal lattice. Additional features deciphered from the current studies
      are: i) robust synthons well-isolated by weak and dispersive interactions reduce
      the material stiffness; in contrast, interweaving of interactions with diverse
      energetics fortifies the crystal packing; ii) mere observation of layered
      structures with orthogonal distribution of strong and weak interactions is a
      prerequisite but inadequate to attain higher plasticity, and iii) interlocked
      molecular arrangements prevent long-range sliding of molecular planes and hence
      lead to enhanced E. Within a broader perspective, the observations are remarkable
      in deriving a molecular basis of the mechanical properties of crystalline solids,
      which can be exploited through crystal engineering for the purposeful design of
      materials with specific properties.

PMID- 30276925
TI  - Direct Differentiation of Stereoisomers of Ezetimibe/Ambrisentan/Atorvastatin and
      their Mechanism Study by Electrospray Ionization Quadurupole Time-of-Flight Mass
      Spectrometry.
AB  - A mass spectrometric method is introduced for rapid and accurate chiral
      quantification by examining a trimeric metal complex into which a chiral
      reference is incorporated with the analyte. Several metal ions (CuII, NiII, MgII,
      MnII, CoII, ZnII) were selected as the central metal ion, and chiral drugs
      ezetimibe (EZM) and ambrisentan (AMB) were used as the reference to each other
      for isomeric differentiation by using electrospray ionization quadrupole time-of
      flight mass spectrometry. Doubly charged trimeric cluster ions instead of the
      singly charged clusters were applied in this study. Kinetic method (KM) and
      chiral recognition (CR) method were used for construction of a calibration curve
      for chiral quantitation. The results from the two methods were found to be
      complementary to each other, which improved quantitative analysis of
      stereoisomers for EZM. Furthermore, we have successfully used S-AMB as reference
      for the chiral differentiation of enantiomeric atorvastatin (ATO), which is
      frequently combined with EZM as a co-drug. Experimental results showed that the
      binary mixture of EZM and ATO enantiomers can be determined simultaneously
      without prior separation steps. The direct measurement of chiral purity within 5%
      was demonstrated. This mass spectrometric method represents an effective
      alternative to commonly used chromatographic techniques as means of chiral purity
      determination and is of potential use in rapid screening experiments.

PMID- 30276926
TI  - A comparative study: visual rating scores and the voxel-based specific regional
      analysis system for Alzheimer's disease on magnetic resonance imaging among
      subjects with Alzheimer's disease, mild cognitive impairment, and normal
      cognition.
AB  - AIM: Hippocampal atrophy shown on magnetic resonance imaging can differentiate
      Alzheimer's disease (AD) patients from subjects with normal cognition (NC).
      Simplified automated methods that use volumetric analysis, such as as the voxel
      based specific regional analysis system for AD, have become widely used in Japan.
      However, the diagnostic value of the voxel-based specific regional analysis
      system compared with visual rating scores for clinical diagnosis is unclear.
      METHODS: Study participants consisted of 37 AD patients, 29 mild cognitive
      impairment (MCI) patients, and 21 NC subjects. All participants underwent
      neuropsychological testing and magnetic resonance imaging. The imaging was scored
      visually for regional brain atrophy by two raters based on a newly developed
      visual rating score. The voxel-based specific regional analysis system for AD
      scores were calculated with the analysis system's advanced software. We analyzed
      whether these scores aid in discriminating among AD, MCI, and NC. RESULTS: The AD
      group had significantly different visual rating scores, regional analysis scores,
      and all neuropsychological test scores than the NC group. The AD group had
      significantly different visual rating scores than the MCI group, and a
      significant difference was observed between the MCI and NC groups on regional
      analysis scores. Both the visual rating and regional analysis scores showed
      equivalent correlations with the neuropsychological test scores. CONCLUSIONS:
      Both the visual rating and regional analysis scores are clinically useful tools
      for differentiating among AD, MCI, and NC.

PMID- 30276927
TI  - Montelukast abrogates prednisolone-induced hepatic injury in rats: Modulation of
      mitochondrial dysfunction, oxidative/nitrosative stress, and apoptosis.
AB  - The aim of this study was to investigate the protective effect of montelukast
      (MTK) against prednisolone-induced hepatic injury in rats. Twenty-eight male
      albino rats were categorized into four equal groups. Group I served as the
      control group; group II: rats orally received prednisolone (5 mg.kg-1 .d-1 ) for
      30 days; groups III and IV: rats orally received MTK at 10 and 20 mg.kg-1 .d-1 ,
      respectively, simultaneously with prednisolone for 30 days. Serum liver enzymes,
      hepatic mitochondrial function, oxidative/nitrosative stress, and inflammatory
      and apoptotic markers were evaluated, and the results were confirmed by
      histopathological examination. MTK showed significant hepatic protection
      evidenced by alleviated histological lesion and improvement of mitochondrial
      function, oxidative/nitrosative stress, and inflammatory and apoptotic changes
      induced by prednisolone, with more profound protection in higher MTK dose (20
      mg.kg-1 ). In view of these findings, we can conclude that MTK may have
      hepatoprotective potential, beyond its therapeutic value for asthmatic patients
      during their course of corticosteroid therapy.

PMID- 30276928
TI  - Monitoring population levels of physical activity and sedentary time in Norway
      across the lifespan.
AB  - PURPOSE: The pandemic of physical inactivity is recognized globally but there is
      a scarcity of studies employing valid and reliable assessment methods of physical
      activity (PA) across the lifespan. The purpose of this study is to provide a
      comprehensive description of objectively measured PA, sedentary time, and
      prevalence of meeting PA recommendations, in a population-based sample of
      Norwegian children, adolescents and adults. METHODS: Children and adolescents (6,
      9 and 15-year-olds) were surveyed in 2011, and adults and older people (20-85
      year-olds) were surveyed in 2014/15, including more than 8000 individuals.
      Anthropometric data were measured in children and adolescents and self-reported
      in the adult sample. PA was assessed by ActiGraph accelerometers for seven
      consecutive days, and PA indices include total PA (counts per minute), intensity
      specific PA, and adherence to PA recommendations. RESULTS: Six-year-olds are 21%
      and 70% more active than 9- and 15-year-olds, respectively (P < 0.001). Nine-year
      olds are 40% more active compared to 15-year-olds (P < 0.001). Moving from
      adolescence (15-year-olds) into adulthood (20-65 years) yields a further
      reduction in total PA by 18%. Among six-, nine- and 15-year olds, 90%, 77%, and
      48% meet the current PA recommendations, respectively, while adherence among
      adults and older people are 33% and 31%, respectively. Overweight and obese
      individuals had lower odds of meeting PA recommendations. CONCLUSIONS: The
      results from the Norwegian surveillance system indicate a strong association
      between age and indices of physical activity. The vast majority of Norwegian
      adults do not meet the PA recommendations and public health action are needed to
      increase PA in Norway.

PMID- 30276929
TI  - Clinical management of the status of atypical endometrial cells using the
      descriptive reporting format for endometrial cytology.
AB  - OBJECTIVE: We aimed to develop and reinforce a clinical management regimen for
      atypical endometrial cell (ATEC) categories within the descriptive reporting
      format for endometrial cytology. METHODS: Between January 2013 and December 2014,
      215 samples, for which histological examination was performed immediately or
      within 3 months after cytology, were cytologically diagnosed as ATEC. For these
      samples, the medical records were retrospectively reviewed to identify risk
      factors for malignancy. RESULTS: Among 152 samples diagnosed as ATEC, of
      undetermined significance, 19 (12.5%) were malignant. In the younger group (age
      <55 years), the chi2 values of body mass index (BMI) >=25 kg/m2 (5.85), gravidity
      (5.64) and parity (5.15) were relatively high, suggesting that these were risk
      factors for malignancy. Of the nulligravida patients, those with BMI >=25 kg/m2 ,
      28% were diagnosed with malignant disease. In the older group (>=55 years),
      endometrial thickening (6.84), atypical genital bleeding (6.43) and BMI >=25
      kg/m2 (3.79) were found to be risk factors for malignancy. Of the patients with
      endometrial thickening and atypical genital bleeding, 67% were diagnosed with
      malignant disease. Among 63 samples diagnosed as ATEC, cannot exclude atypical
      endometrial hyperplasia or more, 35 (55.6%) samples were positive for malignancy.
      CONCLUSIONS: High-risk patients diagnosed with ATEC, of undetermined significance
      were identified. Endometrial biopsy should be considered for nulligravida
      patients aged <55 years with a BMI >=25 kg/m2 .

PMID- 30276930
TI  - Abnormal esophageal motility during a solid test meal in systemic sclerosis
      detection even in very early disease and association with disease progression.
AB  - OBJECTIVE: This study assessed whether high-resolution manometry (HRM) with a
      test meal can detect clinically relevant, abnormal motility already in very early
      systemic sclerosis (SSc) and whether this finding is associated with subsequent
      disease progression. METHODS: This prospective, longitudinal cohort study
      recruited 68 consecutive SSc patients (group #1: 32 established disease (ACR,
      American College of Rheumatology /EULAR, The European League against Rheumatism
      2013 and ACR 1980 criteria fulfilled); group #2: 24 early disease (only ACR/EULAR
      2013 fulfilled); group #3: 12 very early disease (clinical expert diagnosis of
      SSc) and 72 healthy controls. HRM evaluated esophageal motility for water
      swallows and a solid test meal. RESULTS: Systemic sclerosis patients had less
      frequent effective esophageal contractions during the test meal compared to
      healthy controls even in very early disease (0.15, 1.0, 2.1 per minute for groups
      #1, #2, and #3, vs 2.5 per minute in health; P < 0.001, P < 0.001, and P <
      0.0085, respectively). Ineffective motility at HRM was associated with a higher
      modified Rodnan skin score at baseline. Moreover, at mean 18 (10-31) months of
      follow-up, the presence of ineffective motility at baseline was associated with
      progression of skin disease (P = 0.01). Cox proportional hazard regression
      analysis identified hypotensive peristalsis in the test meal (<15% effective
      solid swallows) and low distal contractile integral (DCI; <400 mm Hg.cm.s) as
      predictors for skin aggravation, but not for new organ involvement. CONCLUSION:
      Ineffective motility during a test meal is present already in patients with very
      early SSc. Findings on HRM studies are associated with disease severity at
      baseline, and low percentage of effective swallows in test meal and low mean DCI
      are both predictors of skin progression during follow-up.

PMID- 30276931
TI  - Cytisine versus varenicline for smoking cessation for Maori (the indigenous
      people of New Zealand) and their extended family: protocol for a randomized non
      inferiority trial.
AB  - BACKGROUND AND AIMS: Cytisine, a nicotinic acetylcholine receptor partial agonist
      (like varenicline) found in some plants, is a low-cost, effective smoking
      cessation medication that may appeal to Maori [the indigenous people of New
      Zealand (NZ)]. The RAUORA trial aims to determine the effectiveness, safety and
      cost-effectiveness of cytisine (Tabex(r) ) versus varenicline (Champix(r) ) for
      smoking cessation in Maori and the whanau (extended family) of Maori. DESIGN:
      Pragmatic, community-based, open-label randomized non-inferiority trial. SETTING:
      Lakes District Health Board region, NZ. PARTICIPANTS: Daily smokers (n = 2140)
      who self-identify as Maori or whanau of Maori, and are: aged >= 18 years,
      motivated to quit smoking in the next 2 weeks, eligible for subsidized
      varenicline, able to provide verbal consent and have daily access to a mobile
      phone/internet. Recruitment uses multi-media advertising. INTERVENTION AND
      COMPARATOR: Participants are randomized (1 : 1 ratio) to receive a prescription
      for 12 weeks of cytisine tablets [following the manufacturer's dosing regimen for
      25 days, then one 1.5-mg tablet every 6 hours (two per day) until 12 weeks] or
      varenicline tablets (following the manufacturer's dosing regimen). Both groups
      receive brief stop-smoking advice from the prescribing doctor and withdrawal
      orientated behavioural support via community-based stop-smoking counselling
      services (frequency, duration and mode of delivery tailored for participants) or
      a research assistant (six weekly 10-15-minute calls). Participants are advised to
      reduce their smoking over the first 4 days of treatment, with day 5 as their
      designated quit-date. MEASUREMENTS: The primary outcome is carbon monoxide
      verified continuous abstinence at 6 months post-quit date. Secondary outcomes at
      1, 3, 6 and 12 months post-quit date include: self-reported continuous
      abstinence, 7-day point prevalence abstinence, cigarettes per day, time to
      (re)lapse, adverse events, treatment adherence/compliance, treatment
      acceptability, nicotine withdrawal/urge to smoke and health-care
      utilization/health-related quality of life. COMMENTS: This trial compares
      cytisine and varenicline when used by the indigenous people of NZ and their
      extended family for smoking cessation.

PMID- 30276932
TI  - Letter to 'Removal of retained products of conception showing marked vascularity
      without uterine artery embolization: Two case reports'.

PMID- 30276933
TI  - Neural correlates of facial emotion processing in infancy.
AB  - In the present study we examined the neural correlates of facial emotion
      processing in the first year of life using ERP measures and cortical source
      analysis. EEG data were collected cross-sectionally from 5- (N = 49), 7- (N =
      50), and 12-month-old (N = 51) infants while they were viewing images of angry,
      fearful, and happy faces. The N290 component was found to be larger in amplitude
      in response to fearful and happy than angry faces in all posterior clusters and
      showed largest response to fear than the other two emotions only over the right
      occipital area. The P400 and Nc components were found to be larger in amplitude
      in response to angry than happy and fearful faces over central and frontal scalp.
      Cortical source analysis of the N290 component revealed greater cortical
      activation in the right fusiform face area in response to fearful faces. This
      effect started to emerge at 5 months and became well established at 7 months, but
      it disappeared at 12 months. The P400 and Nc components were primarily localized
      to the PCC/Precuneus where heightened responses to angry faces were observed. The
      current results suggest the detection of a fearful face in infants' brain can
      happen shortly (~200-290 ms) after the stimulus onset, and this process may rely
      on the face network and develop substantially between 5 to 7 months of age. The
      current findings also suggest the differential processing of angry faces occurred
      later in the P400/Nc time window, which recruits the PCC/Precuneus and is
      associated with the allocation of infants' attention.

PMID- 30276934
TI  - The ontogeny of intent-based normative judgments.
AB  - When evaluating norm transgressions, children begin to show some sensitivity to
      the agent's intentionality around preschool age. However, the specific
      developmental trajectories of different forms of such intent-based judgments and
      their cognitive underpinnings are still largely unclear. The current studies,
      therefore, systematically investigated the development of intent-based normative
      judgments as a function of two crucial factors: (a) the type of the agent's
      mental state underlying a normative transgression, and (b) the type of norm
      transgressed (moral versus conventional). In Study 1, 5- and 7-year-old children
      as well as adults were presented with vignettes in which an agent transgressed
      either a moral or a conventional norm. Crucially, she did so either
      intentionally, accidentally (not intentionally at all) or unknowingly
      (intentionally, yet based on a false belief regarding the outcome). The results
      revealed two asymmetries in children's intent-based judgments. First, all age
      groups showed greater sensitivity to mental state information for moral compared
      to conventional transgressions. Second, children's (but not adults') normative
      judgments were more sensitive to the agent's intention than to her belief. Two
      subsequent studies investigated this asymmetry in children more closely and found
      evidence that it is based on performance factors: children are able in principle
      to take into account an agent's false belief in much the same way as her
      intentions, yet do not make belief-based judgments in many existing tasks (like
      that of Study 1) due to their inferential complexity. Taken together, these
      findings contribute to a more systematic understanding of the development of
      intent-based normative judgment.

PMID- 30276935
TI  - Neural correlates of time distortion in a preaction period.
AB  - An intention to move distorts the perception of time. For example, a visual
      stimulus presented during the preparation of manual movements is perceived longer
      than actual. Although neural mechanisms underlying this action-induced time
      distortion have been unclear, here we propose a new model in which the distortion
      is caused by a sensory-motor interaction mediated by alpha rhythm. It is
      generally known that viewing a stimulus induces a reduction in amplitude of
      occipital 10-Hz wave ("alpha-blocking"). Preparing manual movements are also
      known to reduce alpha power in the motor cortex ("mu-suppression"). When human
      participants prepared movements while viewing a stimulus, we found that those two
      types of classical alpha suppression interacted in the third (time-processing)
      region in the brain, inducing a prominent decrease in alpha power in the
      supplementary motor cortex (SMA). Interestingly, this alpha suppression in the
      SMA occurred in an asymmetric manner (such that troughs of alpha rhythm was more
      strongly suppressed than peaks), which can produce a gradual increase (slow shift
      of baseline) in neural activity. Since the neural processing in the SMA encodes a
      subjective time length for a sensory event, the increased activity in this region
      (by the asymmetric alpha suppression) would cause an overestimation of elapsed
      time, resulting in the action-induced time distortion. Those results showed a
      unique role of alpha wave enabling communications across distant (visual, motor,
      and time-processing) regions in the brain and further suggested a new type of
      sensory-motor interaction based on neural desynchronization (rather than
      synchronization).

PMID- 30276936
TI  - Bradyrhizobium and Pseudomonas strains obtained from coal-mining areas nodulate
      and promote the growth of Calopogonium muconoides plants used in the reclamation
      of degraded areas.
AB  - AIMS: The objective of this work was to isolate and characterize indigenous
      rhizobia from coal-mining areas able to efficiently nodulate and fix nitrogen in
      association with Calopogonium mucunoides (calopo). METHODS AND RESULTS:
      Isolation, authentication and morphological, biochemical and molecular
      characterization of the autochthonous rhizobia were performed and their symbiotic
      efficiency (SE) evaluated. Efficient rhizobial isolates suitable for the
      inoculation of calopo in coal-mining regions were obtained. A total of 30
      isolates were obtained after nodulation authentication, of which five presented
      high SE with plant-growth promoting traits such as indole-3-acetic acid
      production, phosphate solubilization and biofilm formation. These isolates were
      identified as belonging to Bradyrhizobium, Pseudomonas and Rhizobium.
      CONCLUSIONS: Bradyrhizobium sp. A2-10 and Pseudomonas sp. A6-05 were able to
      promote calopo plant growth using soil obtained from coal-mining degraded areas,
      thus indicating their potential as inoculants aiming at land reclamation.
      SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first report
      of Pseudomonas nodule formation in calopo. Furthermore, the results demonstrated
      that autochthonous rhizobia obtained from degraded soils presented high SE in
      calopo and possess a wide range of plant-growth promoting traits. Ultimately,
      they may all contribute to an increased leguminous plant growth under stress
      conditions. The selected rhizobia strains may be used as inoculants and present a
      valuable role in the development of strategies aiming to recover coal-mining
      degraded areas. Bacterial inoculants would greatly reduce the use of often
      harmful nitrogen fertilizers vastly employed in revegetation programmes of
      degraded areas.

PMID- 30276937
TI  - Primary effusion lymphoma of the pleural space: Report of a rare complication of
      cardiac transplant with review of the literature.
AB  - Primary effusion lymphoma (PEL) is a rare mature B-cell non-Hodgkin's lymphoma
      arising in body cavities and presenting with effusions. It has been described
      predominantly in patients with impaired immunity from the acquired
      immunodeficiency syndrome and is associated with the Human Herpesvirus-8 (HHV-8).
      Seldom has PEL been diagnosed in persons negative for the human immunodeficiency
      virus (HIV), and in such cases it has occurred primarily in the setting of
      posttransplant immunosuppression. We report an instructive case of a Caribbean
      American HIV-negative orthotopic heart transplant recipient with a history of HHV
      8-associated Kaposi's sarcoma who developed HHV-8 viremia and PEL of the pleural
      space early in the posttransplant course. This case highlights the importance of
      considering PEL in the differential diagnosis of a new pleural effusion in a
      transplant recipient at risk for HHV-8-associated disease.

PMID- 30276938
TI  - N6 -Methyladenosine-Sensitive RNA-Cleaving Deoxyribozymes.
AB  - Deoxyribozymes are synthetic enzymes made of DNA that can catalyze the cleavage
      or formation of phosphodiester bonds and are useful tools for RNA biochemistry.
      Herein, we report new RNA-cleaving deoxyribozymes to interrogate the methylation
      status of target RNAs, thereby providing an alternative method for the
      biochemical validation of RNA methylation sites containing N6 -methyladenosine,
      which is the most wide-spread and extensively investigated natural RNA
      modification. The developed deoxyribozymes are sensitive to the presence of N6 
      methyladenosine in RNA near the cleavage site. One class of these DNA enzymes
      shows faster cleavage of methylated RNA, while others are strongly inhibited by
      the modified nucleotide. The general applicability of the new deoxyribozymes is
      demonstrated for several examples of natural RNA sequences, including a lncRNA
      and a set of C/D box snoRNAs, which have been suggested to contain m6 A as a
      regulatory element that influences RNA folding and protein binding.

PMID- 30276939
TI  - Cognitive activity in a sitting position is protectively associated with
      cognitive impairment among older adults.
AB  - AIM: Previous studies have obtained inconsistent results regarding the
      association between sedentary behavior and cognitive impairment. The present
      study aimed to examine the association between cognitive activity in a sitting
      position (CAS) and cognitive impairment among older adults. METHODS: Community
      dwelling older adults, from Obu or Nagoya in Japan, participated in a survey in
      2013. A total of 5300 participants (mean age 75.0 +/- 5.1 years; women 52.9%) met
      the criteria for the present study. We assessed the frequency and variety of CAS
      composed of six activities, including reading books or newspapers, writing a
      diary or letters, solving crossword puzzles, playing board games, using a
      computer and maintaining housekeeping records. The frequency of engagement in CAS
      was one or more time(s)/week. The variety of CAS was assessed by the number of
      engagements in CAS. Cognitive impairment was defined by two or more tests at
      least 1.5 standard deviations below the reference threshold in four
      neuropsychological tests. Logistic regression analysis was carried out to examine
      the associations between the frequency and variety of CAS and cognitive
      impairment, adjusted for covariates. RESULTS: The proportion of participants
      engaging in each CAS varied from 12.3% (playing board games) to 93.6% (reading
      books or newspaper). After adjustment, five CAS were significantly associated
      with cognitive impairment (OR 0.33-0.65, all P < 0.001). The variety of CAS was
      significantly associated with the reduced OR of cognitive impairment (OR 0.61,
      95% confidence interval 0.55-0.68). CONCLUSIONS: Almost every CAS and a greater
      variety of CAS are associated with cognitive impairment among older people.
      Geriatr Gerontol Int 2018; **: **-**.

PMID- 30276940
TI  - A review on biocide reduced susceptibility due to plasmid-borne antiseptic
      resistant genes-special notes on pharmaceutical environmental isolates.
AB  - Biocides (antiseptics and disinfectants) are widely used in hospitals and
      pharmaceutical industries for contamination control. The emergence of reduced
      susceptibility to biocides is the major concern and this is caused by various
      factors, among which plasmid-mediated resistance is common. Many publications
      describe the antibiotic resistance and mechanisms in a clinical setting. However,
      there are only limited studies available worldwide addressing the molecular
      mechanisms of biocide resistance in the pharmaceutical sector. In addition, there
      is a considerable lack of scientific reports regarding minimum inhibitory
      concentration (MIC) values of typical biocides against pharmaceutical cleanroom
      environmental isolates. This review analyses the plasmid-mediated resistance in
      typical pharmaceutical micro-organisms and prevalence of biocide-resistant genes
      among common clinical and pharmaceutical isolates. This review discusses the MIC
      values of biocides in pharmaceutical environmental isolates, indicating the
      importance of the correlation between the presence or absence of biocide
      resistant genes and reduced susceptibility of MIC values. This review recommends
      that pharmaceutical organizations adopt policies and test methodologies to
      examine the MICs of common cleanroom biocides against the most common types of
      cleanroom environmental isolates.

PMID- 30276941
TI  - Impact of probiotic Lactobacillus sp. on autochthonous lactobacilli in weaned
      piglets.
AB  - AIMS: This study aimed to determine whether host-adapted lactobacilli exhibit
      superior survival during intestinal transit relative to nomadic and free-living
      organisms, and to characterize the impact of probiotic lactobacilli on
      autochthonous lactobacilli. METHODS AND RESULTS: Mixed cultures of Lactobacillus
      casei K9-1 and Lactobacillus fermentum K9-2, or reutericyclin producing
      Lactobacillus reuteri and its isogenic mutant were fed to piglets as freeze-dried
      culture, or as part of fermented feed. Lactobacilli in digesta and faecal samples
      were quantified by strain-specific quantitative PCR (qPCR), high-resolution
      melting curve qPCR, and high-throughput sequencing of 16S rRNA gene sequence
      tags. The abundance of the host adapted L. reuteri in digesta and faeces was
      higher (P < 0.05) when compared to L. casei or L. fermentum. Feed fermentation or
      chemical acidification of feed reduced (P < 0.05) cell counts of Lactobacillus
      salivarius in colonic digesta. The reutericyclin producing L. reuteri TMW1.656
      transiently reduced (P < 0.05) the faecal abundance of lactobacilli. However, the
      overall impact of probiotic intervention on autochthonous lactobacilli was minor.
      CONCLUSIONS: The vertebrate host-adapted L. reuteri survives better during
      intestinal transit of piglets compared to L. casei and L. fermentum. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Ecology and lifestyle of Lactobacillus strains may be
      suitable criteria for selection of probiotic strains for use in swine production.

PMID- 30276942
TI  - Limits to species richness in terrestrial communities.
AB  - Are communities limited by biotic interactions, or are they random draws from
      regional species pools? One way to tell is to compare total species counts in
      geographic regions to average counts in ecological samples falling within those
      regions. If species richness is limited regionally, then the relationship should
      be curvilinear even in a log-log space. Global sets of samples including trees
      and 10 groups of animals are analysed to test this hypothesis. Most relationships
      are indeed curvilinear. To explain these patterns, a simple model is proposed
      that invokes biotic interaction-limited speciation or immigration rates combined
      with extinction or extirpation rates that fall as the number of occupied patches
      increases. Local and regional richness come into balance as the rates trade off,
      causing global richness to also be limited. Surprisingly, however, the data for
      trees break the pattern, suggesting that the great adaptive radiation of seed
      plants may still be unfolding.

PMID- 30276943
TI  - Simultaneous OPCAB and carotid artery endarterectomy for a mobile floating
      plaque.

PMID- 30276944
TI  - Palladium-Catalyzed Divergent Cyclopropanation by Regioselective Solvent-Driven
      C(sp3 )-H Bond Activation.
AB  - Reported is a tandem palladium-catalyzed Heck/regioselective C(sp3 )-H activation
      reaction for the divergent synthesis of spiro- and fused-cyclopropanated
      indolines from N-methallylated 2-bromoarylamides. The regioselectivity of the C-H
      bond activation in the sigma-alkylPdII intermediate is controlled by the solvent
      used. DFT calculations suggest that the polarity of solvent molecules could
      influence the transition-state energy, leading to a bifurcation of the C-H bond
      activation in the sigma-alkylPdII intermediate.

PMID- 30276945
TI  - Conformational Dynamics in the Core of Human Y145Stop Prion Protein Amyloid
      Probed by Relaxation Dispersion NMR.
AB  - Microsecond to millisecond timescale backbone dynamics of the amyloid core
      residues in Y145Stop human prion protein (PrP) fibrils were investigated by using
      15 N rotating frame (R1rho ) relaxation dispersion solid-state nuclear magnetic
      resonance spectroscopy over a wide range of spin-lock fields. Numerical
      simulations enabled the experimental relaxation dispersion profiles for most of
      the fibril core residues to be modelled by using a two-state exchange process
      with a common exchange rate of 1000 s-1 , corresponding to protein backbone
      motion on the timescale of 1 ms, and an excited-state population of 2 %. We also
      found that the relaxation dispersion profiles for several amino acids positioned
      near the edges of the most structured regions of the amyloid core were better
      modelled by assuming somewhat higher excited-state populations (~5-15 %) and
      faster exchange rate constants, corresponding to protein backbone motions on the
      timescale of ~100-300 MUs. The slow backbone dynamics of the core residues were
      evaluated in the context of the structural model of human Y145Stop PrP amyloid.

PMID- 30276946
TI  - Decreased perfusion of the posterior cingulate gyri shown by a cingulate island
      score is a possible marker of vulnerability to behavioural and psychological
      symptoms of Alzheimer's disease: a pilot study.
AB  - BACKGROUND: The cingulate island score (CIScore), which indicates the Z-score
      ratio of the posterior cingulate gyri to the medial occipital area, has been
      shown to be useful for differentiating dementia with Lewy bodies from Alzheimer's
      disease (AD). Our aim was to investigate associations between the clinical
      symptoms of AD and the CIScore as an index of the relative decrease in perfusion
      of the posterior cingulate gyri that occurs in the early stages of AD. METHODS:
      Seventeen patients with early-stage AD and 13 patients with amnesic mild
      cognitive impairment were examined. Z-score maps of technetium-99m ethyl
      cysteinate dimer single-photon emission computed tomography images acquired from
      the patients were converted, and the CIScore was determined by using the easy Z
      score imaging system. The relationships between the CIScore and clinical symptom
      scores were tested. RESULTS: A significant correlation was identified between the
      CIScore and the Neuropsychiatric Inventory Questionnaire score. No significant
      correlations were identified between the CIScore and other measures of cognitive
      function. Based on a CIScore of 0.39, we correctly differentiated patients with
      and without behavioural and psychological symptoms of dementia (BPSD), with a
      sensitivity of 72.2% and specificity of 75.0%. DISCUSSION: Using technetium-99m
      ethyl cysteinate dimer single-photon emission computed tomography, we observed
      that decreased posterior cingulate gyri perfusion, relative to the medial
      occipital area, in prodromal and early AD was closely associated with behavioural
      and psychological symptoms of dementia. Therefore, our findings suggest that
      CIScore is not only useful for discriminating dementia with Lewy bodies from AD,
      but it can also be clinically used as a specific indicator of the vulnerability
      to behavioural and psychological symptoms of dementia in the early stages of AD.

PMID- 30276947
TI  - Raman spectroscopy for the preoperative diagnosis of thyroid cancer and its
      subtypes: An in vitro proof-of-concept study.
AB  - OBJECTIVE: In 2016, there were an estimated 56 870 new cases of thyroid cancer
      (TC) in the USA. Fine needle aspiration cytology (FNAC) is the most safe,
      accurate and cost-effective method for the initial investigation of thyroid
      nodules. FNAC is limited by the inability to diagnose malignancy in follicular
      patterned lesions accurately and, as a result, 20%-30% of cases under
      investigation for TC are classified as cytologically indeterminate, illustrating
      a problem with current FNAC procedure. Raman spectroscopy has shown promising
      results for the detection of many cancers; however, to date there has been no
      report on the performance of Raman spectroscopy on thyroid cytological samples.
      The aim of this study was to examine whether Raman spectroscopy could be used to
      correctly classify cell lines representing benign thyroid cells and various
      subtypes of TC. METHODS: A benign thyroid cell line and seven TC cell lines were
      prepared as ThinPrep(r) cytology slides and analysed with Raman spectroscopy.
      Principal components analysis and linear discriminant analysis were implemented
      to develop effective diagnostic algorithms for classification of Raman spectra of
      different TC subtypes. RESULTS: The spectral differences separating benign and TC
      cell lines were assigned to differences in the composition of nucleic acids,
      lipids, carbohydrates and protein in the benign and cancer cells. Good
      sensitivities (74%-85%), specificities (65%-93%) and diagnostic accuracies (71%
      88%) were achieved for the identification of TC. CONCLUSION: These findings
      suggest that Raman spectroscopy has potential for preoperative TC diagnosis on
      FNAC samples.

PMID- 30276948
TI  - Carbon-carbon and Carbon-heteroatom Bond Formation Reactions using Unsaturated
      Carbon Compounds.
AB  - The carbon-carbon and carbon-heteroatom bond formation reactions are considered
      as a fundamental tool in synthetic organic chemistry. They have been effectively
      utilized in the synthesis of medicinally significant molecules, agrochemicals and
      valuable compounds in material sciences. This has been primarily enabled by
      highly efficient protocols arising from divergent mechanistic pathways. In this
      personal account, we aim to discuss some recent advances in carbon-carbon or
      carbon-heteroatom bond formation reactions to which our group has actively
      contributed. More specifically, this record focuses on the use of unsaturated
      carbon compounds for the construction of C-C and C-X bonds.

PMID- 30276949
TI  - Mannich-type Reactions of Cyclic Nitrones: Effective Methods for the
      Enantioselective Synthesis of Piperidine-containing Alkaloids.
AB  - Even though there are dozens of biologically active 2-substituted and 2,6
      disubstituted piperidines, only a limited number of approaches exist for their
      synthesis. Herein is described two Mannich-type additions to nitrones, one using
      beta-ketoacids under catalyst-free conditions and another using methyl ketones in
      the presence of chiral thioureas, which can generate a broad array of such 2
      substituted materials, as well as other ring variants, in the form of beta-N
      hydroxy-aminoketones. Both processes have broad scope, with the latter providing
      products with high enantioselectivity (up to 98 %). The combination of these
      methods, along with other critical steps, has enabled 8-step total syntheses of
      the 2,6-disubstituted piperidine alkaloids (-)-lobeline and (-)-sedinone.

PMID- 30276950
TI  - Choose preterm breech delivery mode individually, case by case.

PMID- 30276952
TI  - Uterine transplantation in transgender women: medical, legal and ethical
      considerations.

PMID- 30276951
TI  - Invasive fungal infections amongst patients with acute-on-chronic liver failure
      at high risk for fungal infections.
AB  - AIMS: To study the prevalence, risk factors, role of serum biomarkers for
      diagnosis and impact of invasive fungal infections (IFIs) in patients with acute
      on-chronic liver failure (ACLF). METHODS: An analysis of IFI in patients with
      ACLF (EASL criteria) was conducted retrospectively. The diagnosis of IFI in
      clinically suspected patients was based on EORTC/MSG criteria. The demographical,
      clinical, laboratory details and outcomes were analysed. RESULTS: Out of 264
      patients with ACLF, 54 (20.4%) patients with suspicion of IFI were evaluated and
      IFI was diagnosed in 39 (14.7%). Invasive candidiasis was documented in 25
      (64.1%) and invasive aspergillosis in 14 (35.8%). The most common source of
      infection was respiratory (n = 13) followed by renal (n = 7) and spontaneous
      fungal peritonitis (n = 6). On univariate analysis, diabetes mellitus,
      hemodialysis, prior antibiotic use, cerebral and respiratory organ failures,
      Chronic Liver Failure Consortium (CLIF-OF and CLIF-C ACLF) scores were predictors
      for development of IFI (P < 0.05). On multivariate analysis, hemodialysis and
      prior antibiotics use predicted the development of IFI (P < 0.05). Non-survivors
      were more likely to have IFI (P = 0.029), high CLIF-OF and CLIF-C ACLF scores (P
      < 0.001; for both) and higher 1,3-beta D Glucan (BDG) levels (P = 0.009). The
      sensitivity, specificity, and AUROC of BDG (80 pg/mL) and Galactomannan index
      (GMI [0.5]) for diagnosing IFI were 97.4%, 60%, 0.770% and 43.6%, 100%, 0.745
      respectively. CONCLUSIONS: Invasive fungal infections constitutes an important
      cause of mortality in ACLF patients. BDG and GMI can be useful markers to guide
      antifungal therapy in patients at high risk for IFI.

PMID- 30276953
TI  - Congenital lumbar hernia-A feature of diabetic embryopathy?
AB  - Congenital lumbar hernia is a rare anomaly consisting of protrusion of abdominal
      organs or extraperitoneal tissue through a defect in the lateral abdominal wall.
      The majority of affected patients have additional anomalies in a pattern
      described as the lumbocostovertebral syndrome. We report four patients born to
      mothers with poorly controlled diabetes with congenital lumbar hernia. All
      patients exhibited features of lumbocostovertebral syndrome with lumbar hernia,
      multiple vertebral segmentation anomalies in the lower thoracic and/or upper
      lumbar spine, rib anomalies, and unilateral renal agenesis. Additional anomalies
      present in the patients included preaxial hallucal polydactyly, abnormal situs,
      and sacral dysgenesis, anomalies known to be associated with diabetic
      embryopathy. At least 11 other patients have been previously reported with the
      lumbocostovertebral syndrome in the setting of maternal diabetes. We suggest that
      congenital lumbar hernia and the lumbocostovertebral syndrome are related to
      diabetic embryopathy.

PMID- 30276954
TI  - Stipulating Low Production Cost Solar Cells All Set to Retail...!
AB  - Today's solar cells are exceptionally in demand whilst excess exploitation of
      natural fossil fuels. In this context, the first and second generation solar
      cells commercially available in market for more than decades however limitations
      in production cost and large-scale applications insist to generate inexpensive
      materials for fabrication. Thereby, organic materials based solar cells explored
      and emerging as third generation solar cells which possess flexibility, low cost
      and large-scale applications. For example, organic photovoltaics, dye sensitized
      solar cells and perovskite (organic-inorganic) solar cells (PSCs) are considered
      third generation solar cells wherein PSCs reached the record power conversion
      efficiency (PCE ~23 %) and durability assists great advantages for
      commercialization in near future. Moreover, we reported various global renowned
      companies involved producing the modules and materials for three generation solar
      cells, hence, majority of companies considered commercialization of perovskite
      based solar cells assist low cost photovoltaics to meet the current energy
      necessities and environmental safety.

PMID- 30276956
TI  - Metal Nanoparticles Supported on Biomass-Derived Hierarchical Porous Heteroatom
      Doped Carbon from Bamboo Shoots: Design, Synthesis and Applications.
AB  - Heteroatom-doped porous carbon derived from biomass have recently received
      increasing attention due to their unique properties such as high electrical
      conductivity, large specific surface area, high porosity, and easy availability,
      which are appealing materials for versatile applications in catalysis, energy,
      separation and adsorption, and life sciences as well. On the basis of our
      previous work in this field, we summarized in this account our recent progress on
      design, synthesis of metal (e. g., Pd, Co) nanoparticles supported heteroatom
      doped hierarchical porous carbon material derived from bamboo shoots and their
      applications for important organic transformations, including chemoselective
      semihydrogenation of alkynes, hydrosilylation of alkynes, cascade synthesis of
      benzofurans from terminal alkynes and iodophenols, selective hydrogenation of
      functionalized nitroarenes to form anilines, imines, and formamides. Finally, the
      current state and future challenges in this field are discussed. We hope this
      account could shed light on the rational design of novel non-noble metal based
      heterogeneous catalysts derived from biomass for efficient and sustainable
      organic transformations.

PMID- 30276957
TI  - Symptom severity, symptom interference and use of complementary and alternative
      medicine among survivors of colorectal and breast cancer after curative treatment
      in Taiwan.
AB  - This study compared symptom severity, symptom interference and use of
      complementary and alternative medicine (CAM) between cancer survivors after
      curative treatment and individuals who did not have cancer. Factors associated
      with CAM use among cancer survivors were examined. A cross-sectional survey was
      conducted of 146 cancer survivors (77 breast and 69 colorectal cancer survivors
      who had completed conventional treatment 1-5 years previously and were cancer
      free) from a hospital's cancer registration system (survivor group), and 161
      healthy individuals without cancer (comparison group). The two groups were
      frequency-matched for sex and age. Findings indicated higher use of CAM in the
      survivor group (54.1%) than the comparison group (36.6%). There were no
      significant differences in overall symptom severity and interference between the
      two groups. Multivariate logistic regression showed that prior use of CAM (OR =
      5.14, 95% CI: 2.34-10.69) and higher symptom interference (OR = 1.04, 95% CI:
      1.001-1.08) were positively related to CAM use in the survivor group. The
      survivors did not have higher symptom severity and symptom interference with
      daily life, but were more likely to use CAM than the comparison group. Medical
      staff should discuss symptom interference and use of CAM with cancer survivors to
      guide them in the appropriate use of CAM.

PMID- 30276955
TI  - Replacement of microglia in the aged brain reverses cognitive, synaptic, and
      neuronal deficits in mice.
AB  - Microglia, the resident immune cell of the brain, can be eliminated via
      pharmacological inhibition of the colony-stimulating factor 1 receptor (CSF1R).
      Withdrawal of CSF1R inhibition then stimulates microglial repopulation,
      effectively replacing the microglial compartment. In the aged brain, microglia
      take on a "primed" phenotype and studies indicate that this coincides with age
      related cognitive decline. Here, we investigated the effects of replacing the
      aged microglial compartment with new microglia using CSF1R inhibitor-induced
      microglial repopulation. With 28 days of repopulation, replacement of resident
      microglia in aged mice (24 months) improved spatial memory and restored physical
      microglial tissue characteristics (cell densities and morphologies) to those
      found in young adult animals (4 months). However, inflammation-related gene
      expression was not broadly altered with repopulation nor the response to immune
      challenges. Instead, microglial repopulation resulted in a reversal of age
      related changes in neuronal gene expression, including expression of genes
      associated with actin cytoskeleton remodeling and synaptogenesis. Age-related
      changes in hippocampal neuronal complexity were reversed with both microglial
      elimination and repopulation, while microglial elimination increased both
      neurogenesis and dendritic spine densities. These changes were accompanied by a
      full rescue of age-induced deficits in long-term potentiation with microglial
      repopulation. Thus, several key aspects of the aged brain can be reversed by
      acute noninvasive replacement of microglia.

PMID- 30276958
TI  - Furfuryl- and Maleimido Polysaccharides: Synthetic Strategies Toward Functional
      Biomaterials.
AB  - In context with facile and efficient syntheses of functional polymeric materials,
      the combination of polysaccharides and functional moieties based on renewable
      resources is a sustainable and valuable approach. This review presents
      alternatives to prominent click reactions utilizing biopolymer derivatives with
      furfuryl and maleimide groups. On the one hand, the cross-linking by Diels-Alder
      reaction of these polymers enables the synthesis of novel materials in the fields
      of self-healing polymers, tissue engineering, and drug delivery. On the other
      hand, thiol-ene click reactions allow their conjugation to complex
      (bio)molecules. Different synthetic strategies are reviewed and the applicability
      of functional materials is evaluated.

PMID- 30276960
TI  - Tropical Medicine & International Health.

PMID- 30276959
TI  - Intention-to-treat analysis of liver transplantation for hepatocellular
      carcinoma: The impact of pre-existing diabetes mellitus.
AB  - BACKGROUND & AIMS: Diabetes mellitus is known to negatively impact the outcome of
      liver transplant; however, data are scarce regarding risk of waitlist dropout and
      tumour recurrence in patients with hepatocellular carcinoma. We examined the
      impact of diabetes mellitus on the outcomes of candidates with hepatocellular
      carcinoma on an intention-to-treat basis. METHODS: Our study included 15 776
      candidates with hepatocellular carcinoma diagnosis on the Scientific Registry of
      Transplant Recipients database from 2008 to 2015 to evaluate the risk of waitlist
      dropout, hepatocellular carcinoma recurrence and overall survival. RESULTS: There
      were more patients dropped out from the waiting list owing to patient disease
      deterioration or tumour progression in the diabetes mellitus group (15.1% vs
      13.7%, P = 0.024). The mean waiting time was similar in the two groups (233 days
      vs 230 days, P = 0.631). The recurrence rate was higher in the diabetes mellitus
      group (9.0% vs 6.2%, P < 0.001); however, the mean time to recurrence in the two
      groups was similar (23.7 months vs 22.6 months, P = 0.371). Diabetes mellitus,
      tumours exceeding Milan criteria, and AFP >400 ng/mL were independent predictive
      factors for recurrence. On an intention-to-treat basis, diabetes mellitus was
      also an independent poor prognostic factor for overall survival; however, the
      overall survival was comparable with tumours beyond Milan criteria. CONCLUSIONS:
      Diabetes mellitus was associated with poor survival outcomes and an increased
      risk of waitlist dropout and tumour recurrence rates in hepatocellular carcinoma
      patients. Those patients should be paid more attention to cardiovascular and
      oncological examination when determining waitlist and post-transplant
      surveillance strategies.

PMID- 30276961
TI  - Applicability of Sepsis-3 criteria and quick Sequential Organ Failure Assessment
      in patients with cirrhosis hospitalised for bacterial infections.
AB  - BACKGROUND & AIMS: An algorithm including Sepsis-3 criteria and quick Sequential
      Organ Failure Assessment (qSOFA) was recently proposed to predict severity of
      infection in cirrhosis. However, its applicability among patients without a
      baseline SOFA available for Sepsis-3 definition is unknown. We sought to
      investigate the applicability and prognostic value of qSOFA and Sepsis-3 criteria
      in patients with cirrhosis hospitalised for bacterial infections, without pre
      hospitalisation SOFA. METHODS: In this cohort study, 164 patients were followed
      up to 30 days. Data collection, including the prognostic models, was performed at
      admission and at day-3. RESULTS: All patients fulfilled Sepsis-3 criteria
      (admission SOFA >= 2) and, therefore, admission Sepsis-3 was not included in
      further analysis. Admission qSOFA was an independent predictor of survival (HR =
      2.271, P = 0.015). For patients initially classified as high risk by qSOFA,
      Chronic Liver Failure - Sequential Organ Failure Assessment (CLIF-SOFA) was the
      only prognostic predictor. Among patients initially classified as low risk by
      qSOFA, the following parameters evaluated at day-3 were independent predictors of
      survival: qSOFA, acute-on-chronic liver failure, and Child-Pugh classification.
      Although not independently related to survival, Sepsis-3 criteria at day-3 was
      associated with lower 30-day survival in Kaplan-Meier analysis (66% vs 85%, P =
      0.008). However, prognosis was better predicted by day-3 qSOFA, with 30-day
      Kaplan-Meier survival probability of 88% when qSOFA < 2 and 24% among those with
      qSOFA >= 2. CONCLUSION: Sepsis-3 criteria evaluated at admission are very limited
      in infected patients with cirrhosis without baseline SOFA. qSOFA was
      independently related to survival and appears to be a valuable tool for
      determining severity of infection and to follow patients initially classified as
      low risk.

PMID- 30276962
TI  - Multicenter study of mortality in achondroplasia.
AB  - Sudden death and higher mortality are recognized in achondroplasia, with acute
      brainstem compression, a common cause of mortality in children <4 years and
      cardiovascular deaths being more prevalent in adults. Although, changes in
      clinical management have improved survival, mortality is still higher than in the
      general population. The aim of this multicenter clinic-based study was to assess
      the rate and causes of mortality in patients seen in clinic since 1986.
      Information was ascertained for achondroplasia patients clinically assessed in
      four skeletal dysplasia clinics. Data was sent to the National Death Index to
      identify vital status and cause of death. Standardized mortality rates (SMR) were
      calculated based on U.S. populations from 1975, 1995, and 2000. Eight hundred
      fifty-five patients were identified, contributing 12,117 person-years and a total
      of 12 deaths. One case died in infancy. In the 1-4 year age group, which had the
      highest age-adjusted SMR, three out of five deaths were because of
      cerebrovascular/cardiovascular events. Half the deaths in ages 5 through 24 were
      because of accidental events, including motor vehicle accidents. Decreased
      mortality in children with achondroplasia was noted, particularly in younger age
      groups. This improvement in childhood survival is outpaced by improved survival
      in the general population. Causes of death in these patients have shifted over
      the last 30 years, with fewer sudden death and deaths because of pneumonia or
      hydrocephalus countered by more cardiovascular or cerebrovascular and accidental
      deaths. Clinicians should be aware of the apparent increased risk of vehicular
      accidents and counsel patients accordingly.

PMID- 30276963
TI  - Women travelling without men, and their health care needs.

PMID- 30276964
TI  - Microvascular circulatory dysregulation driven in part by cystathionine gamma
      lyase: A new paradigm for cardiovascular compromise in the preterm newborn.
AB  - OBJECTIVE: H2 S may explain the dysregulation of microvascular tone associated
      with poor outcome following preterm birth. In adult vasculature, H2 S is
      predominantly produced by CSE. We hypothesized that vascular CSE activity
      contributes to microvascular tone regulation during circulatory transition.
      METHODS: Preterm (GA62) and full-term (GA69) guinea pig fetuses and neonates were
      studied. Microvascular blood flow was assessed by laser Doppler flowmetry.
      Thiosulfate, primary urinary metabolite of H2 S, was determined by high
      performance liquid chromatography. Real-time H2 S production was assessed using a
      microrespiration system in fetal and postnatal (10, 24 hours) skin and heart
      samples. CSE contribution was investigated by inhibition via propargylglycine.
      RESULTS: In preterm animals, postnatal H2 S production capacity in peripheral
      vasculature increased significantly and was significantly reduced by the
      inhibition of CSE. Urinary thiosulfate correlated with both microvascular blood
      flow and capacity of the vasculature to produce H2 S. H2 S produced via CSE did
      not correlate directly with microvascular blood flow. CONCLUSIONS: In preterm
      neonates, H2 S production increases during fetal-to-neonatal transition and CSE
      contribution to total H2 S increases postnatally. CSE-dependent mechanisms may
      therefore underpin the increase in H2 S production over the first 72 hours of
      life in preterm human neonates, associated with both central and peripheral
      cardiovascular instability.

PMID- 30276965
TI  - In vitro and in vivo antischistosomal activities of chalcones.
AB  - In this study, we evaluated the in vitro and in vivo schistosomicidal activities
      of chalcones against Schistosoma mansoni worms. In vitro assays revealed that
      chalcones 1 and 3 were the most active compounds, without affecting significantly
      mammalian cells. Confocal laser scanning microscopy and scanning electron
      microscopy studies revealed reduction on the numbers of tubercles and
      morphological alterations in the tegument of S. mansoni worms after in vitro
      incubation with chalcones 1 and 3. In a mouse model of schistosomiasis, the oral
      treatment (400 mg/kg) with chalcone 1 or 3 significantly caused a total worm
      burden reduction in mice. Chalcone 1 showed significant inhibition of the S.
      mansoni ATP diphosphohydrolase activity, which was corroborated by molecular
      docking studies. Results suggested that chalcones could be explored as lead
      compounds with antischistosomal properties.

PMID- 30276966
TI  - Genetic analyses of differences between solid and nonsolid predominant lung
      adenocarcinomas.
AB  - BACKGROUND: Solid predominant lung adenocarcinomas (LUAD) have distinct
      histopathological and clinical characteristics compared with nonsolid subtypes. A
      comprehensive comparison of altered genes found in solid and nonsolid subtypes
      has not previously been performed. In this study, we analyzed differences in gene
      expression, genetic mutations, and DNA methylation to better understand the risk
      factors for these two subtypes of LUAD. METHODS: Differentially expressed genes
      (DEGs) and differentially mutated genes (DMGs) were analyzed from RNA-seq data
      downloaded from The Cancer Genome Atlas (TCGA) and Broad Institute database. To
      understand the functional significance of molecular changes, we examined the DEGs
      and DMGs with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway
      analysis. RESULTS: A total of 184 patients in the TCGA cohort and 140 patients in
      the Broad Institute cohort were included in this study. We identified 75 DEGs, of
      which 15 were upregulated and 56 downregulated in the solid group relative to the
      nonsolid group. The DEGs were mainly involved in the regulation of water and
      fluid transport. We discovered 38 significantly differentially expressed genes
      that overlapped in the two groups. The DMGs were mainly enriched for pathways
      involved in cell-cell adhesion, cell adhesion, biological adhesion, and
      hemophilic cell adhesion. We additionally discovered nine significantly
      methylated genes between solid and nonsolid LUAD. CONCLUSIONS: Our study
      identified distinct DEGs, DMGs, and methylation genes for solid and nonsolid LUAD
      subtypes. These findings improve our understanding of the different
      carcinogenesis mechanisms in LUAD and will help to develop new therapeutic
      strategies.

PMID- 30276967
TI  - Use of beta-blocker is associated with lower mortality in patients with coronary
      artery disease with or without COPD.
AB  - INTRODUCTION: Beta-blockers are indicated for secondary prevention of coronary
      artery disease (CAD). However, in patients with co-morbidity of chronic
      obstructive pulmonary disease (COPD) an underuse of beta-blocker has been
      reported. MATERIALS AND METHODS: Prescription and demographic data and
      information on hospital discharge diagnoses from 13 Austrian health insurance
      funds for the years 2006-2007 were analyzed. The primary end point was all-cause
      mortality of patients with CAD with or without COPD and its association with use
      of beta-blockers. RESULTS: In 2006 and 2007, 65717 patients (37% female, 63%
      male) were discharged with a diagnosis of CAD. Among these patients, 46% had a co
      diagnosis of COPD, 24% had diabetes, and 75% received beta-blockers. Use of beta
      blockers was comparable in CAD patients with COPD and without COPD with 77% and
      74%, respectively. Thousand eight hundred seventy-two (8.1%) and 1473 (5.6%)
      patients with and without COPD, who used beta-blockers died within months in 2006
      and 2007. Thousand five hundred fifty-three (22.0%) and 1862 (22.2%) of patients
      with and without COPD and without beta-blockers died during the corresponding
      time period. DISCUSSION: Use of beta-blockers was similar in patients with CAD
      with or without co-diagnosis of COPD. However, mortality of beta-blocker users
      was markedly lower than that of nonusers in patients with CAD with or without
      COPD.

PMID- 30276968
TI  - Bitterless guaifenesin prodrugs-design, synthesis, characterization, in vitro
      kinetics, and bitterness studies.
AB  - A respected number of drugs suffer from bitter taste which results in patient
      incompliance. With the aim of solving the bitterness of guaifenesin, dimethyl
      maleate, maleate, glutarate, succinate, and dimethyl succinate prodrugs were
      designed and synthesized. Molecular orbital methods were utilized for the design
      of the ester prodrugs. The density functional theory (DFT) calculations revealed
      that the hydrolysis efficiency of the synthesized prodrugs is significantly
      sensitive to the pattern of substitution on C=C bond and distance between the
      nucleophile and the electrophile. The hydrolysis of the prodrugs was largely
      affected by the pH of the medium. The experimental t1/2 for the hydrolysis of
      guaifenesin dimaleate ester prodrugs in 1N HCl was the least and for guaifenesin
      dimethyl succinate was the highest. Functional heterologous expression of
      TAS2R14, a broadly tuned bitter taste receptor responding to guaifenesin, and
      experiments using these prodrugs revealed that, while some of the prodrugs still
      activated the receptor similarly or even stronger than the parent substance,
      succinate derivatization resulted in the complete loss of receptor responses. The
      predicted binding modes of guaifenesin and its prodrugs to the TAS2R14 homology
      model suggest that the decreased activity of the succinate derivatives may be
      caused by a clash with Phe247.

PMID- 30276970
TI  - Disaccharide-Based Anionic Amphiphiles as Potent Inhibitors of Lipopolysaccharide
      Induced Inflammation.
AB  - Despite significant advances made in the last decade in the understanding of
      molecular mechanisms of sepsis and in the development of clinically relevant
      therapies, sepsis remains the leading cause of mortality in intensive care units
      with increasing incidence worldwide. Toll-like receptor 4 (TLR4)-a transmembrane
      pattern-recognition receptor responsible for propagating the immediate immune
      response to Gram-negative bacterial infection-plays a central role in the
      pathogenesis of sepsis and chronic inflammation-related disorders. TLR4 is
      complexed with the lipopolysaccharide (LPS)-sensing protein myeloid
      differentiation-2 (MD-2) which represents a preferred target for establishing new
      anti-inflammatory treatment strategies. Herein we report the development, facile
      synthesis, and biological evaluation of novel disaccharide-based TLR4?MD-2
      antagonists with potent anti-endotoxic activity at micromolar concentrations. A
      series of synthetic anionic glycolipids entailing amide-linked beta-ketoacyl
      lipid residues was prepared in a straightforward manner by using a single
      orthogonally protected nonreducing diglucosamine scaffold. Suppression of the LPS
      induced release of interleukin-6 and tumor necrosis factor was monitored and
      confirmed in human immune cells (MNC and THP1) and mouse macrophages. Structure
      activity relationship studies and molecular dynamics simulations revealed the
      structural basis for the high-affinity interaction between anionic glycolipids
      and MD-2, and highlighted two compounds as leads for the development of potential
      anti-inflammatory therapeutics.

PMID- 30276972
TI  - Contributions of regulated transcription and mRNA decay to the dynamics of gene
      expression.
AB  - Organisms have acquired sophisticated regulatory networks that control gene
      expression in response to cellular perturbations. Understanding of the mechanisms
      underlying the coordinated changes in gene expression in response to external and
      internal stimuli is a fundamental issue in biology. Recent advances in high
      throughput technologies have enabled the measurement of diverse biological
      information, including gene expression levels, kinetics of gene expression, and
      interactions among gene expression regulatory molecules. By coupling these
      technologies with quantitative modeling, we can now uncover the biological roles
      and mechanisms of gene regulation at the system level. This review consists of
      two parts. First, we focus on the methods using uridine analogs that measure
      synthesis and decay rates of RNAs, which demonstrate how cells dynamically change
      the regulation of gene expression in response to both internal and external cues.
      Second, we discuss the underlying mechanisms of these changes in kinetics,
      including the functions of transcription factors and RNA-binding proteins.
      Overall, this review will help to clarify a system-level view of gene expression
      programs in cells. This article is categorized under: Regulatory
      RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Turnover and Surveillance >
      Regulation of RNA Stability RNA Methods > RNA Analyses in vitro and In Silico.

PMID- 30276971
TI  - First data from a parent-reported registry of 81 individuals with Coffin-Siris
      syndrome: Natural history and management recommendations.
AB  - Coffin-Siris syndrome (CSS; MIM 135900) is a multisystem congenital anomaly
      syndrome caused by mutations in the genes in the Brg-1 associated factors (BAF)
      complex. Classically, individuals with CSS have been described with hypo- or
      aplasia of the fifth digit nails or phalanges (hence the term "fifth digit
      syndrome"). Other physical features seen include growth restriction, coarse
      facial features, hypertrichosis or hirsutism, sparse scalp hair, dental
      anomalies, and other organ-system abnormalities. Varying degrees of developmental
      and intellectual delay are universal. To date, approximately 200 individuals have
      been described in the literature. With the advent of large-scale genetic testing
      such as whole-exome sequencing is becoming more available, more individuals are
      being found to have mutations in this pathway, and the phenotypic spectrum
      appears to be broadening. We report here a large cohort of 81 individuals with
      the diagnosis of CSS from the first parent-reported CSS/BAF complex registry in
      an effort to describe this variation among individuals, the natural history of
      the syndrome, and draw some gene-phenotype correlations. We propose that changes
      in the BAF complex may represent a spectrum of disorders, including both ARID1B
      related nonsyndromic intellectual disability (ARID1B-ID) and CSS with classic
      physical features. In addition, we offer surveillance and management
      recommendations based on the medical issues encountered in this cohort to help
      guide physicians and patients' families.

PMID- 30276969
TI  - Evaluation of the prognostic value of surgery and postoperative radiotherapy for
      patients with thymic neuroendocrine tumors: A propensity-matched study based on
      the SEER database.
AB  - BACKGROUND: The prognostic value of surgery and postoperative radiotherapy (PORT)
      for primary thymic neuroendocrine tumors (TNETs) was estimated using the SEER
      database. METHODS: This retrospective study used SEER data of TNET patients
      between 1998 and 2015. Propensity score matching (PSM) was performed according to
      whether surgery was performed. The prognostic effects on overall survival (OS)
      and cancer-specific survival (CSS) were evaluated using multivariate Cox
      regression. RESULTS: A total of 3947 patients were included: 293 (7.4%) TNET,
      2788 (70.6%) thymoma, and 866 (21.9%) thymic carcinoma. Compared to other
      subtypes, TNET patients were younger, included a larger proportion of men, had a
      well or moderately differentiated histological grade, higher disease stage at
      diagnosis, and were more likely to have regional lymph node metastasis. The
      median OS and CSS for TNET were 82.9 (95% confidence interval 74.3-91.4) and
      101.9 (95% confidence interval 91.9-111.8) months, respectively, significantly
      shorter than for thymomas. In the matched cohort of TNET patients, multivariate
      analysis of OS and CSS revealed a significantly poorer prognosis in the non
      surgery group (P < 0.001). Compared to total/radical resection, TNET patients who
      underwent debulking resection had significantly inferior outcomes (P < 0.05).
      Postoperative radiotherapy favorably impacted OS and CSS in Masaoka-Koga stage
      III-IV TNET patients; this OS impact was also observed in stage IIB patients.
      CONCLUSION: TNETs are extremely rare with relatively dismal outcomes. This
      analysis revealed the role of complete surgical resection and the favorable
      effect of postoperative radiotherapy in specific TNET subgroups.

PMID- 30276973
TI  - Human omental adipose-derived stem cells from donors with different body mass
      index had similar effects on proliferation and migration of endometrial cancer
      cells in vitro.
AB  - AIM: This study aimed to confirm whether human omental adipose-derived stem cells
      (O-ASC) from donors with varying body mass index (BMI, calculated in kg/m2 )
      exert different effects on proliferation and migration of endometrial cancer (EC)
      cells. METHODS: Omental adipose-derived stem cells were isolated from the omental
      adipose tissues of eight patients who were diagnosed with EC aged from 35 to 56
      years. According to the patients' BMI, the O-ASC was divided into two groups:
      obesity group (BMI >= 30) and normal group (18.5 < BMI <= 24.9). A broad spectrum
      cytokine antibody array was used to measure 62 paracrine cytokines secreted by
      all the O-ASC. MTS assays, direct and indirect co-culture assays were used to
      assess the effects of O-ASC on proliferation and migration of Hec-1A (estrogen
      receptor-/progesterone receptor-) and Ishikawa (estrogen receptor+/progesterone
      receptor+) EC cells. RESULTS: Eight samples of O-ASC were successfully isolated
      including four samples in obesity group and four in normal group. All the O-ASC
      displayed typical characteristics of mesenchymal stem cells and possessed similar
      secretory functions as 26 cytokines were identified in condition medium of O-ASC
      based on cytokine antibody array. The proliferation of Ishikawa cells was gently
      stimulated by O-ASC from the two groups (P < 0.05) whereas without any effects on
      Hec-1A cells. Both horizontal and vertical migrations of EC cells were promoted
      by O-ASC (P < 0.01). However, there were no statistical differences between the
      two groups. CONCLUSION: Human O-ASC could influence the proliferation and
      migration of EC cells in vitro but the effects were not modified by donors' BMI.

PMID- 30276975
TI  - ISPAD Clinical Practice Consensus Guidelines 2018: Limited Care Guidance
      Appendix.

PMID- 30276974
TI  - Adjuvant radiotherapy, chemotherapy or surgery alone for high-risk histological
      node negative esophageal squamous cell carcinoma: Protocol for a multicenter
      prospective randomized controlled trial.
AB  - Histologically node negative esophageal squamous cell carcinoma (pN0 ESCC) after
      radical resection still carries a significant risk of recurrence, especially in
      high-risk patients. Our previous study showed that the risk of recurrence was
      associated with tumor location and cell differentiation, as well as the presence
      of lymphovascular invasion. Most recurrence occurs within two years after
      surgery. There is still a lack of knowledge on the risks or potential benefits of
      postoperative adjuvant therapies for high-risk pN0 ESCC patients. This study was
      designed to evaluate the efficacy and toxicity of adjuvant therapies after
      radical surgery in high-risk patients with pN0 ESCC. This study is a multicenter,
      prospective, controlled randomized trial, which will compare the differences
      between either adjuvant chemotherapy or adjuvant radiotherapy and surgery alone
      for high-risk pN0 ESCC. Patients in group A will receive three cycles of adjuvant
      chemotherapy with paclitaxel and cisplatin, patients in group B will receive
      adjuvant radiotherapy with intensity-modulated radiation of 50 Gy, and patients
      in group C (the control) will receive surgery alone. The primary endpoint is
      three-year disease-free survival. Secondary endpoints include toxicity of
      adjuvant therapies and five-year overall survival. One hundred and sixty-two
      patients in each group are required and a total of 486 patients will finally be
      enrolled into the study. This will be the first randomized trial to investigate
      the necessity or potential benefit of postoperative adjuvant therapies for high
      risk pN0 ESCC patients.

PMID- 30276976
TI  - ISPAD Clinical Practice Consensus Guidelines 2018: What is new in diabetes care?

PMID- 30276977
TI  - Six-week pretreatment with growth hormone improves clinical outcomes of poor
      ovarian responders undergoing in vitro fertilization treatment: A self-controlled
      clinical study.
AB  - AIM: The purpose was to explore whether the 6 weeks of growth hormone (GH)
      pretreatment could increase the live birth rate of poor ovarian responders (POR).
      METHODS: This self-controlled, retrospective study was performed among 380 POR
      who had GH adjuvant (GH+) at a university-affiliated hospital in Guangzhou,
      China, from October 2010 to April 2016. Growth hormone was injected daily
      beginning with the previous menstruation and maintained until ovum pickup, for
      approximately 6 weeks. Clinical variables between the GH+ cycle and the other GH
      free (GH-) cycle of each patient were compared. Both cycles were conducted with a
      similar conventional control ovarian hyperstimulation protocol for in vitro
      fertilization treatment. One to one case-control matching was performed to adjust
      essential confounding factors between GH+ cycles and GH- cycles. RESULTS: GH
      pretreatment improved embryo quality (1.14 +/- 1.50 vs 0.11 +/- 0.48, P < 0.05)
      and decreased miscarriage (18.8% vs 80.0%, P < 0.05) significantly, resulting in
      an increase in the live birth rate (23.5% vs 3.9%, P < 0.05). The oocyte
      utilization rate in GH+ cycles was remarkably improved, even with older patients
      and more failed previous attempts. Significant improvement in embryo quality was
      shown by an increased number of good-quality embryos and improved oocyte
      utilization rate after matching. CONCLUSIONS: The longer term use of low-dose GH
      administration for 6 weeks could be beneficial for the utilization of oocytes and
      for finally increasing the live birth rates of POR.

PMID- 30276978
TI  - Half-sandwich Iridium(III) Benzimidazole-Appended Imidazolium-Based N
      heterocyclic Carbene Complexes and Antitumor Application.
AB  - A series of half-sandwich iridium(III) benzimidazole-appended imidazolium-based N
      heterocyclic carbene (NHC) antitumor complexes [(eta5 -Cpx )Ir(C^N)Cl]Cl, where
      Cpx is pentamethylcyclopentadienyl (Cp*) or its biphenyl derivative (Cpxbiph )
      and C^N is a NHC chelating ligand, were successfully synthesized and
      characterized. The IrIII complexes showed potential antitumor activity against
      A549 cells, at most three times more potent than cis-platin under the same
      conditions. Complexes could bind to BSA by a static quenching mode, catalyzing
      the change of NADH to NAD+ and inducing the production of reactive oxygen species
      (maximum turnover number, 9.8), which play an important role in regulating cell
      apoptosis. Confocal microscopy showed that the complexes could specifically
      target lysosomes in cells with a Pearson's co-localization coefficient 0.76 and
      0.72 after 1 h and 6 h, respectively, followed an energy-dependent cellular
      uptake mechanism and damaged the integrity of lysosomes. At the same time,
      complexes caused a marked loss of mitochondrial membrane potential.

PMID- 30276980
TI  - Strong responses from weakly interacting species.
AB  - The impact of species loss from competitive communities partly depends on how
      populations of the surviving species respond. Predicting the response should be
      straightforward using models that describe population growth as a function of
      competitor densities; but these models require accurate estimates of interaction
      strengths. Here, we quantified how well we could predict responses to competitor
      removal in a community of annual plants, using a combination of observation and
      experiment. It was straightforward to fit models to multi-species communities,
      which passed standard diagnostic tests and provided apparently sensible estimates
      of interaction strengths. However, the models consistently underpredicted the
      response to competitor removal, by a factor of at least 50%. We argue that this
      poor predictive ability is likely to be general in plant communities due to 'the
      ghost of competition present' that confines species to parts of the environment
      in which they compete best.

PMID- 30276979
TI  - Lung brain metastasis pseudoprogression after nivolumab and ipilimumab
      combination treatment.
AB  - Immunotherapy has revolutionized the treatment of non-small cell lung cancer;
      however, its role in the treatment response of lung brain metastasis is unknown.
      Understanding immunotherapy activity in the central nervous system is important
      in order to avoid additional toxicity, such as that associated with the use of
      cerebral radiotherapy. We present two cases with clinical and radiological
      progression with increases in size and perilesional edema of brain lesions after
      treatment with a combination of ipilimumab and nivolumab. The increasing use of
      immunotherapy in lung cancer requires increased knowledge of new patterns of
      radiological response, such as pseudoprogression.

PMID- 30276981
TI  - Creatinine excretion in consecutive urine samples after controlled ingestion of
      water.
AB  - Highly diluted urine is among the most commonly observed factors affecting the
      validity of urine testing for drug abuse. A minimum creatinine concentration of
      20 mg/dL urine has been proposed as a marker for dilution of a urine sample. This
      study investigates the effect of water consumption on creatinine concentration,
      as well as its effect on specific gravity and osmolality. In this study, 22
      subjects (17 women and 5 men) were included to determine the influence of sex and
      weight on the impact of excessive water consumption on these markers of urine
      dilution. The subjects consumed 0.5 L, 1.0 L, and 1.5 L of water, respectively,
      within 15 minutes. The mean minimum creatinine concentrations (Jaffe reaction)
      for the void 2 hours after fluid intake were 60.4 mg/dL, 15.8 mg/dL, and 10.9
      mg/dL for the respective ingested volumes of water. Mean creatinine
      concentrations excreted by men were significantly higher than those excreted by
      women. Participants with a weight below 60 kg tended to excrete lower urine
      creatinine concentrations. 50% of the volunteers with a BMI < 20 kg/m2 and 20% of
      the volunteers with a BMI > 20 kg/m2 exhibited creatinine concentrations below
      the threshold value of 20 mg/dL. A similar pattern was established for gravity
      and osmolality. Due to its simple determination, creatinine may be preferred over
      specific gravity or osmolality. In order to evaluate the internal dilution of a
      urine sample for legally defensible drug testing, it may be necessary to account
      for sex and body weight.

PMID- 30276982
TI  - Noncanonical features and modifications on the 5'-end of bacterial sRNAs and
      mRNAs.
AB  - Although many eukaryotic transcripts contain cap structures, it has been long
      thought that bacterial RNAs do not carry any special modifications on their 5'
      ends. In bacteria, primary transcripts are produced by transcription initiated
      with a nucleoside triphosphate and are therefore triphosphorylated on 5'-ends.
      Some transcripts are then processed by nucleases that yield monophosphorylated
      RNAs for specific cellular activities. Many primary transcripts are also
      converted to monophosphorylated species by removal of the terminal pyrophosphate
      for 5'-end-dependent degradation. Recent studies surprisingly revealed an
      expanded repertoire of chemical groups on 5'-ends of bacterial RNAs. In addition
      to mono- and triphosphorylated moieties, some mRNAs and sRNAs contain cap-like
      structures and diphosphates on their 5'-ends. Although incorporation and removal
      of these groups have become better understood in recent years, the physiological
      significance of these modifications remain obscure. This review highlights recent
      studies aimed at identification and elucidation of novel modifications on the 5'
      ends of bacterial RNAs and discusses possible physiological applications of the
      modified RNAs. This article is categorized under: RNA Turnover and Surveillance >
      Regulation of RNA Stability RNA Structure and Dynamics > RNA Structure, Dynamics,
      and Chemistry RNA Processing > Capping and 5' End Modifications.

PMID- 30276984
TI  - The diagnostic value of cell blocks in liquid-based cytology of bronchial
      aspiration and bronchial brushing materials: Methodological issues.

PMID- 30276983
TI  - Academic performance in adolescents aged 15-16 years born after frozen embryo
      transfer compared with fresh embryo transfer: a nationwide registry-based cohort
      study.
AB  - OBJECTIVE: To assess academic performance in singletons aged 15-16 years
      conceived after frozen embryo transfer (FET) compared with singletons born after
      fresh embryo transfer (ET) in Danish cohorts born from 1995 to 2001. DESIGN:
      Danish national registry-based cohort study. SETTING: Danish national registries.
      POPULATION: All 6495 singletons conceived after assisted reproductive technology
      (ART) treatment in Denmark from 1995 to 2001 [FET (n) = 423; fresh ET (n) =
      6072]. METHODS: Mean test scores on a national standardised and international
      comparable grading-scale. Comparisons of test score were first made in univariate
      analysis (Model 1) and secondly in a multivariate linear model (Model 2)
      adjusting for relevant reproductive and socio-demographic covariates such as the
      occupational and educational level of the parents. Sensitivity analyses on FET
      IVF (in vitro fertilisation) versus fresh ET-IVF and FET-ICSI (intracytoplasmic
      sperm injection) versus fresh ET-ICSI were made. Linear mixed models were used to
      account for the correlation in test scores of siblings for continuous outcome.
      MAIN OUTCOME MEASURES: Mean overall test score and test score in Danish,
      mathematics, English, and physics/chemistry. RESULTS: Crude and adjusted mean
      test scores were similar for adolescents conceived after FET compared with fresh
      ET. The crude mean difference was +0.11 (95% CI -0.11; 0.34), and the adjusted
      mean difference was +0.12 (95% CI -0.09; 0.34). CONCLUSIONS: Adolescents
      conceived after FET had similar academic performance at 15-16 of years of age
      compared with children conceived after fresh ET. TWEETABLE ABSTRACT: Using frozen
      embryos in fertility treatment does not affect school performance in Danish
      adolescents aged 15-16 years.

PMID- 30276985
TI  - Construction of Linear and Branched Tetraboranes by 1,1- and 1,2-Diboration of
      Diborenes.
AB  - Sterically unencumbered diborenes based on a benzylphosphine chelate undergo
      diboration reactions with bis(catecholato)diboron in the absence of a catalyst to
      yield tetraboranes. The symmetrical diborenes studied undergo 1,2-diborations,
      whereas an unsymmetrical derivative was found to yield a triborylborane-phosphine
      adduct as the result of a formal 1,1-diboration. A related borylborylene compound
      also underwent a 1,2-diboration to produce a borylene-borane adduct.

PMID- 30276988
TI  - The IDEAL and the EQUATOR.

PMID- 30276986
TI  - "Non-Naked" Gold with Glucose Oxidase-Like Activity: A Nanozyme for Tandem
      Catalysis.
AB  - It has been widely reported that "naked" gold nanoparticles (Au NPs) without
      protectors have glucose oxidase (GOx)-like activity, and the use of protectors
      can inhibit the GOx-like activity. Here, "non-naked" Au NPs with GOx-like
      activity are synthesized by using protein as protector. Although "naked" Au NPs
      have peroxidase-like activity and GOx-like activity, the optimal pH ranges of the
      both activities are obviously different. Fortunately, as-synthesized "non-naked"
      Au NPs show the dual enzyme-like activities at the same pH. So, "non-naked" Au
      NPs can be described as "tandem nanozyme." As another bonus, the participation of
      protein protector can stabilize the GOx-like activity and make Au NPs modifiable.
      Even though Au NPs are connected with graphene oxide (GO), the GOx-like activity
      is still not changed. Further, Au NPs-GO nanocomposites are applied on the one
      pot nonenzymatic glucose colorimetric detection. The "non-naked" gold not only
      broadens the species of tandem nanozymes, but also facilitates the
      functionalization of nanozymes, which is promising for immunoassay, biosensor,
      and medical treatment.

PMID- 30276990
TI  - ESCP President's Report.

PMID- 30276991
TI  - Management of patients with incurable colorectal cancer: a retrospective audit by
      Thavanesan N et al.

PMID- 30276994
TI  - Re: Small bowel obstruction and perforation following ingestion of an oyster
      shell.

PMID- 30276993
TI  - Time to die: choice or chance.

PMID- 30276996
TI  - 25, 50 & 75 years ago.

PMID- 30276995
TI  - Response to Re: Wound tension and 'closability' with keystone flaps, V-Y flaps
      and primary closure: a study in fresh-frozen cadavers.

PMID- 30276997
TI  - Progress towards a sustainable clinical academic training pathway.

PMID- 30276998
TI  - Monitoring outcomes in spine surgery: rationale behind the Australian Spine
      Registry.

PMID- 30276999
TI  - Re: Wound tension and 'closability' with keystone flaps, V-Y flaps and primary
      closure: a study in fresh-frozen cadavers.

PMID- 30277000
TI  - Is modern perioperative care too complicated for surgeons?

PMID- 30277001
TI  - Is robotic radical cystectomy ready for prime time?

PMID- 30277002
TI  - Bullying in surgery: will it help the speciality?

PMID- 30277003
TI  - Re: Patients requiring an acute operation: where are the delays in the process?

PMID- 30277004
TI  - Patterns and factors associated with low adherence to psychotropic medications
      during pregnancy-A cross-sectional, multinational web-based study.

PMID- 30277005
TI  - Preservation of Blood Vessels with an Oxygen Generating Composite.
AB  - Damage caused by oxygen deficiency (hypoxia) is one of the major factors limiting
      tissue and organ preservation time. Cooling tissues slows down metabolic rate of
      cells thereby prolonging tissue and organ survival sufficiently to allow
      transport and transplantation within a few hours. Although metabolism is slowed,
      cells and some enzymes continue to consume oxygen that can render cold stored
      tissues hypoxic. Here, an oxygen-generating composite (OGC) with sustained oxygen
      release is reported for ex vivo blood vessel preservation. Aorta segments are
      cultured under hypothermia for 25 days in vascular preservation media. The
      presence of OGC increases cell viability from 9 +/- 6% to 96 +/- 3% and retains
      65 +/- 8% of original KCl stimulated contractile force after 25 days compared
      with 25 +/- 4% in controls. Culture for 7 days in nitrogen demonstrates proof-of
      concept for normothermic blood vessel preservation, OGC increases the cell
      viability from 45 +/- 15% to 78 +/- 2%, and KCl stimulates contractile force from
      49 +/- 7% to 95 +/- 8%, respectively. Oxygen release materials then may have a
      role in augmenting current preservation techniques.

PMID- 30277007
TI  - Generation and characterization of anti-citrullinated protein antibody-producing
      B-cell clones from rheumatoid arthritis patients.
AB  - OBJECTIVE: Anti-citrullinated protein antibodies (ACPA) are a hallmark for
      rheumatoid arthritis (RA). Autoantigen-specific B-cell function aside from
      autoantibody production remains poorly understood in the context of this disease.
      We set out to elucidate this function through the isolation and immortalization
      of unique citrullinated protein or peptide (CP)-reactive B-cell clones from RA
      patients. METHODS: B-cell clones from either blood or synovial fluid of cyclic
      citrullinated peptide 2 (CCP2)+ RA patients were immortalized by genetic
      reprogramming with Bcl6 and Bcl-xL. ELISA and flow cytometry were used to
      identify CCP2-reactive clones and to further characterize surface marker and
      cytokine expression as well as B-cell receptor (BCR) signaling competence. Global
      gene expression profiles were interrogated by RNA sequencing. RESULTS: We
      generated three unique CP-reactive memory B-cell clones from two RA patients. CP
      reactive memory B cells did not appear to be broadly cross-reactive, but rather
      had a fairly restricted epitope recognition profile. These clones can secrete
      both pro- and anti-inflammatory cytokines and have a unique surface profile of
      costimulatory molecules and receptors, including CD40 and C5aRI, when compared to
      non-CP-reactive clones from the same patient. Additionally, CP-reactive clones
      bind citrullinated but not native protein and can mobilize calcium in response to
      antigen binding. CONCLUSIONS: CP-reactive memory B cells comprise a rare,
      seemingly oligoclonal population with restricted epitope-specificity and distinct
      phenotypic and molecular characteristics suggestive of antigen-presenting cells.
      Cloning by genetic reprogramming opens new avenues to study the function of
      autoreactive memory B cells, especially in terms of antigen processing,
      presentation and subsequent T-cell polarization. This article is protected by
      copyright. All rights reserved.

PMID- 30277006
TI  - Would 1.0 cm be a more suitable cutoff to subdivide pT1 tumors in hormone
      receptor-negative and HER2-positive breast cancer?
AB  - BACKGROUND: HER2+ and hormone receptor (HoR)-negative breast cancer usually
      associated with poor outcome. However, it remained elusive for the prognosis of
      small (T1a-T1c) HER2+/HoR- breast cancer. The present study retrospectively
      analyzed the Surveillance, Epidemiology, and End Results (SEER) database to
      explore the clinicopathological characteristics and prognosis of T1a-T1c
      HER2+/HoR- breast cancer. MATERIAL AND METHODS: Data for patients diagnosed with
      either HER2-/HoR+or HER2+/HoR- T1a-T1c breast cancer between 2010 and 2012 were
      obtained from SEER program. Survival analyses were conducted by Kaplan-Meier
      method and Cox proportion hazard regression. RESULTS: Totally, 2648 HER2+/HoR-
      and 56387 HER2-/HoR+T1a-T1c breast cancer patients were enrolled. There was a
      clear trend that tumor size had a positive correlation with advanced AJCC stage
      (P < 0.001) and N-stage (P < 0.001). T1a and T1b HER2+/HoR- breast cancer had
      great homogeneity in that these two subgroups had comparable survival and both
      showed no significant survival difference with its counterpart of HER2
      /HoR+subtype. Conversely, T1c HER2+/HoR- breast cancers revealed worse prognosis
      than T1a/T1b HER2+/HoR- and T1c HER2-/HoR+tumors (BCSS HR 3.847, P < 0.001; OS HR
      2.055, P < 0.001). CONCLUSION: T1a and T1b HER2+/HoR- breast cancer had favorable
      prognosis and great homogeneity, indicating 1.0 cm may be a suitable cutoff for
      subclassification of T1 cancer. Future randomized clinical trials were warranted
      to verify this hypothesis and elucidate the biological behavior of small T1 tumor
      to facilitate precise medicine.

PMID- 30277008
TI  - Adoptive Regulatory T Cell Therapy in a Patient with Systemic Lupus
      Erythematosus.
AB  - OBJECTIVE: Regulatory T cell (Treg) adoptive cell therapy has great potential to
      treat autoimmune disease. Currently, very little is known about how these cells
      impact inflamed tissues. The purpose of this study was to elucidate how
      autologous Treg therapy influences tissue inflammation in human autoimmune
      disease. METHODS: We describe a patient with systemic lupus erythematosus (SLE)
      with active skin disease that received adoptive Treg therapy. We comprehensively
      quantify Tregs and immune activation in peripheral blood and skin with time post
      treatment. RESULTS: Deuterium tracking of infused Tregs revealed the transient
      presence of cells in peripheral blood accompanied by increased percentages of
      highly activated Tregs in diseased skin. Flow cytometric analysis and whole
      transcriptome RNA sequencing (RNAseq) revealed that Treg accumulation in skin was
      associated with a marked attenuation of the IFNgamma pathway and a reciprocal
      augmentation of the IL-17 pathway. This phenomenon was more pronounced in skin
      relative to peripheral blood. To validate these findings, we found that Treg
      adoptive transfer in a murine model of skin inflammation also resulted in a
      pronounced skewing away from Th1 immunity and towards IL-17 production.
      CONCLUSIONS: We report the first case of a patient with SLE treated with
      autologous adoptive Treg therapy. Taken together, our results suggest that this
      treatment results in increased activated Tregs in inflamed skin with a dynamic
      shift from Th1 to Th17 responses. This article is protected by copyright. All
      rights reserved.

PMID- 30277009
TI  - Modulating Electronic Structures of Inorganic Nanomaterials for Efficient
      Electrocatalytic Water Splitting.
AB  - Electrocatalytic water splitting is one of the most promising sustainable energy
      conversion technologies, but is limited by the sluggish electrochemical
      reactions. Inorganic nanomaterials have been widely used as efficient catalysts
      for promoting the electrochemical kinetics. Several approaches to optimize
      activities of these nanocatalysts have been developed. The electronic structures
      of the catalysts play a pivotal role in governing the activity and thus have been
      identified as an essential descriptor. However, the underlying working mechanisms
      related to the refined electronic structures remain elusive. To establish the
      structure-electronic behavior-activity relationship, a comprehensive overview of
      the developed strategies to regulate the electronic structures is presented,
      emphasizing the surface modification, strain, phase transition and
      heterostructure. Current challenges to the fundamental understanding of electron
      behaviors in the nanocatalysts are fully discussed.

PMID- 30277010
TI  - The green microalga Lobosphaera incisa harbours an arachidonate 15S-lipoxygenase.
AB  - The green microalga Lobosphaera incisa is an oleaginous eukaryotic alga that is
      rich in arachidonic acid (20:4). Being rich in this polyunsaturated fatty acid
      (PUFA), however, makes it sensitive to oxidation. In plants, lipoxygenases (LOXs)
      are the major enzymes that oxidise these molecules. Here, we describe, to our
      best knowledge, the first characterisation of a cDNA encoding a LOX (LiLOX) from
      a green alga. To obtain first insights into its function, we expressed it in E.
      coli, purified the recombinant enzyme and analysed its enzyme activity. The
      protein sequence suggests that LiLOX and plastidic LOXs from bryophytes and
      flowering plants may share a common ancestor. The fact that LiLOX oxidises all
      PUFAs tested with a consistent oxidation on the carbon n-6, suggests that PUFAs
      enter the substrate channel through their methyl group first (tail first).
      Additionally, LiLOX form the fatty acid hydroperoxide in strict S configuration.
      LiLOX may represent a good model to study plastid LOX, because it is stable after
      heterologous expression in E. coli and highly active in vitro. Moreover, as the
      first characterised LOX from green microalgae, it opens the possibility to study
      endogenous LOX pathways in these organisms.

PMID- 30277011
TI  - Specific association of HLA-DRB1*03 with anti-carbamylated protein antibodies in
      patients with RA.
AB  - OBJECTIVES: The new RA-specific autoantibodies, the anti-carbamylated protein
      antibodies (ACarPA), provide an opportunity to improve management and
      understanding of RA. However, many questions remain about them, including their
      relationship with HLA-DRB1 alleles. MATERIAL AND METHODS: The samples of 1126 RA
      patients from three collections were obtained. Serum reactivity against in vitro
      carbamylated FCS proteins was determined by ELISA. HLA-DRB1 alleles were
      determined by either hybridization techniques or imputation from HLA dense
      genotypes. These results were combined by meta-analysis with data from three
      previously reported cohorts. The carrier frequencies of the common HLA-DRB1
      alleles were compared between the antibody-positive subgroups and the double
      negative subgroup in ACPA/ACarPA stratified patients, and between the four
      patient strata and the healthy controls. RESULTS: Meta-analysis was conducted
      with 3709 RA patients and 2305 healthy subjects. It revealed a significant
      increase of HLA-DRB1*03 carriers in the ACPA- /ACarPA+ subgroup in comparison
      with both ACPA- /ACarPA- patients and healthy controls that was consistent in the
      six sample collections. This association was independent of the SE and the
      analyzed confounders. No other allele was specifically associated with ACPA-
      /ACarPA+ patients. In contrast, the SE was significantly increased in the ACPA+
      /ACarPA- and ACPA+ /ACarPA+ patient subgroups without distinction between them.
      Also, some alleles (including HLA-DRB1*03) were associated with protection from
      ACPA+ RA. CONCLUSION: A specific association of HLA-DRB1*03 with ACPA- /ACarPA+
      RA has been identified that suggests preferential presentation of carbamylated
      peptides as a new mechanism for HLA contribution to RA susceptibility. This
      article is protected by copyright. All rights reserved.

PMID- 30277012
TI  - A PAX3/BRN2 rheostat controls the dynamics of BRAF mediated MITF regulation in
      MITFhigh /AXLlow melanoma.
AB  - The BRAF kinase and the MAPK pathway are targets of current melanoma therapies.
      However, MAPK pathway inhibition results in dynamic changes of downstream targets
      that can counteract inhibitor-action not only in during treatment, but also in
      acquired resistant tumours. One such dynamic change involves the expression of
      the transcription factor MITF, a crucial regulator of cell survival and
      proliferation in untreated as well as drug-addicted acquired resistant melanoma.
      Tight control over MITF expression levels is required for optimal melanoma
      growth, and while it is well established that the MAPK pathway regulates MITF
      expression, the actual mechanism is insufficiently understood. We reveal here,
      how BRAF through action on the transcription factors BRN2 and PAX3 executes
      control over the regulation of MITF expression in a manner that allows for
      considerable plasticity. This plasticity provides robustness to the BRAF mediated
      MITF regulation and explains the dynamics in MITF expression that are observed in
      patients in response to MAPK inhibitor therapy.

PMID- 30277013
TI  - What's hot, what's new: Report from the American Transplant Congress 2018.
AB  - The American Transplant Congress (ATC) 2018 event brought over 5000 attendees to
      Seattle, WA in June 2018. As the joint meeting of the American Society of
      Transplant Surgeons (ASTS) and the American Society of Transplantation (AST), the
      Congress provides exposures to cutting-edge scientific research findings for a
      diverse mix of physicians, surgeons, scientists, nurses, organ procurement
      personnel, advanced transplant providers, pharmacists, administrators, and other
      transplant professionals. The 5-day event featured nearly 1800 abstracts, over
      500 oral presentations, and more than 1200 poster presentations, all delivered in
      a way that encouraged the exchange of new clinical and scientific information and
      supported an interchange of opinions regarding care management and socioeconomic,
      ethical, and regulatory issues relevant to organ and tissue transplantation. We
      present here the outstanding abstracts presented at ATC2018 divided into 3
      categories of basic, translational, and clinical research.

PMID- 30277014
TI  - Needleless Transcutaneous Neuromodulation Accelerates Postoperative Recovery
      Mediated via Autonomic and Immuno-Cytokine Mechanisms in Patients With
      Cholecystolithiasis.
AB  - BACKGROUND: Postsurgical gastrointestinal disturbance is clinically characterized
      by the delayed passage of flatus and stool, delayed resumption of oral feeding,
      dyspepsia symptoms, and postsurgical pain. This study was designed 1) to evaluate
      the effects of needleless transcutaneous neuromodulation (TN) on postoperative
      recovery; 2) to investigate mechanisms of the TN involving autonomic functions in
      postoperative patients after removal of the gallbladder. METHODS: Sixty patients
      scheduled for laparoscopic cholecystectomy (LC) were randomized to TN (n = 30)
      and sham-TN (n = 30). TN was performed via acupoints ST36 and PC6 for 30 min
      twice daily from 24 hours before surgery to 72 hours after surgery. Sham-TN was
      performed using the same parameters at nonacupoints. RESULTS: 1) Compared to sham
      TN, TN shortened time to first flatulence (38.9 +/- 4.0 vs. 24.9 +/- 2.4 hour, p
      = 0.004) and time to defecation (63.1 +/- 4.5 vs. 42.5 +/- 3.1 hour, p < 0.001).
      2) Compared to sham-TN, TN increased the percentage of normal pace-making
      activity (66.2 +/- 2.2 vs. 73.8 +/- 2.3%, p = 0.018). 3) TN enhanced vagal
      activity. Compared to that 24 hours before surgery, surgery decreased vagal
      activity (HF) (0.41 +/- 0.02 vs. 0.34 +/- 0.02, p = 0.043) 3 hours after the
      operation. Compared to sham-TN, TN increased HF (0.45 +/- 0.02 vs. 0.52 +/- 0.02,
      p = 0.045) 72 hours after the operation. Further, HF was negatively correlated
      with time to defecation and serum norepinephrine. 4) Surgery increased serum IL-6
      (1.1 +/- 0.1 before surgery vs. 2.9 +/- 0.7 pg/mL, p = 0.041) 72 hours after the
      operation, which was reduced to baseline by TN (0.9 +/- 0.1). CONCLUSIONS: In
      conclusion, the proposed needleless TN accelerates postoperative recovery after
      LC, possibly mediated via the autonomic and immune-cytokine mechanisms.
      Needleless and self-administrable TN may be an easy-to-implement and low-cost
      complementary therapy for postoperative recovery.

PMID- 30277015
TI  - Association of hypocalcemia with congenital heart disease in 22q11.2 deletion
      syndrome.
AB  - Hypocalcemia is one of the cardinal features of the chromosome 22q11.2 deletion
      syndrome (22q11.2DS), the most common cause of DiGeorge syndrome. Hypocalcemia
      and other features of 22q11.2DS including congenital heart disease (CHD) are
      primarily ascribed to problems with morphogenesis and function of the pharyngeal
      arch system derivatives including the parathyroid glands, the aortic arch, and
      the cardiac outflow tract. In light of the aforementioned embryology, we
      hypothesized that hypocalcemia would be identified more frequently in those
      patients with 22q11.2DS and CHD. We conducted a retrospective IRB approved chart
      review on 1,300 subjects with 22q11.2DS evaluated at the Children's Hospital of
      Philadelphia. chi2 test was used to evaluate the statistical significance of
      differences in hypocalcemia between the two groups. Eight hundred fifty-two
      patients had calcium levels available for review. Of these, 466 (54.69%) had a
      history of hypocalcemia and 550 (64.55%) had CHD. Of those with CHD, 343 (62.36%)
      had a history of hypocalcemia, and of those without CHD, only 123 (40.73%) had a
      history of hypocalcemia. Thus, the frequency of diagnosed hypocalcemia was
      greater in patients with 22q11.2DS and CHD as compared to those without CHD (p <
      .001). We also analyzed age of onset of hypocalcemia and found that 66.47% of
      CHD/hypocalcemia group had neonatal/infantile hypocalcemia versus 43.09% in the
      non-CHD/hypocalcemia group. In our large cohort of patients with 22q11.2DS, the
      prevalence of diagnosed hypocalcemia is elevated among patients with CHD, in whom
      it is more likely to be diagnosed during the neonatal/infancy period.

PMID- 30277017
TI  - Plaques and tumors in a patient with refractory Sezary syndrome treated with
      mogamulizumab.

PMID- 30277016
TI  - Clinical complete response after chemoradiotherapy for carcinoma of thoracic
      esophagus: Is esophagectomy always necessary? A systematic review and meta
      analysis.
AB  - BACKGROUND: Although a clinical complete response (cCR) after chemoradiotherapy
      (CRT) could lead to a better prognosis, the choice of a following strategy, such
      as surgical or non-surgical approach, remains controversial. METHODS: All
      articles relevant to a comparison of surgical and non-surgical treatment
      (including further definitive chemoradiotherapy or active surveillance) for
      esophageal carcinoma patients with a cCR after CRT were retrieved for meta
      analysis. The final date for data retrieval was 30 June 2018. RESULTS: Four
      retrospective studies including 648 patients met the inclusion criteria: 620 with
      squamous cell carcinoma and 28 with adenocarcinoma. The CRT + surgery group had
      an advantage over the non-surgery group in regard to two-year disease-free
      survival (DFS); however, the two groups showed similar results in five-year DFS.
      The CRT + surgery group had an advantage over the non-surgery group in two-year
      overall survival (OS); nevertheless, the two groups showed similar results in
      five-year OS. CONCLUSIONS: Based on the available evidence, the addition of
      surgery to thoracic locally advanced esophageal carcinoma patients with a cCR
      after neoadjuvant CRT provided no advantage to long-term survival. As an
      exception, the two-year DFS and OS could be improved. This research conclusion
      might be more suitable to patients with squamous cell carcinoma.

PMID- 30277018
TI  - A neurofibroma-like tumor in a giant congenital nevus.

PMID- 30277019
TI  - Enabling Reversible (De)Lithiation of Aluminum by using Bis(fluorosulfonyl)imide
      Based Electrolytes.
AB  - Aluminum, a cost-effective and abundant metal capable of alloying with Li up to
      around 1000 mAh g-1 , is a very appealing anode material for high energy density
      lithium-ion batteries (LIBs). However, despite repeated efforts in the past three
      decades, reports presenting stable cycling performance are extremely rare. This
      study concerns recent findings on the highly reversible (de)lithiation of a micro
      sized Al anode (m-Al) by using bis(fluorosulfonyl)imide (FSI)-based electrolytes.
      By using this kind of electrolyte, m-Al can deliver a specific capacity over 900
      mAh g-1 and superior Coulombic efficiency (96.8 %) to traditional carbonate- and
      glyme-based electrolytes (87.8 % and 88.1 %, respectively), which represents the
      best performance ever obtained for an Al anode without sophisticated structure
      design. The significantly improved electrochemical performance, which paves the
      way to realizing high-performance Al-based high energy density LIBs, can be
      attributed the peculiar solid-electrolyte interphase (SEI) formed by the FSI
      containing electrolyte.

PMID- 30277021
TI  - Current trends in nursing science theory: Editorial on the Nursing Research
      Special Issue.

PMID- 30277020
TI  - Analyzing Integrin-Dependent Adhesion.
AB  - In this unit, methods for the analysis of integrin-dependent adhesion are
      described. Two major types of assays are commonly used for this analysis. The
      first are cell adhesion assays. A key application of this type of assay is to
      identify which integrin(s) mediate cell-substrate interactions; a comprehensive
      list of antibodies suitable for this purpose is detailed. The second are solid
      phase assays in which purified integrins and integrin ligands are used. These
      assays can be used, e.g., to measure apparent affinities of integrins for
      different ligands and IC50 values of pharmacological inhibitors. Curr. Protoc.
      Cell Biol. 53:9.4.1-9.4.17. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30277022
TI  - The Chemistry and Properties of Energetic Materials Bearing [1,2,4]Triazolo[4,3
      b][1,2,4,5]tetrazine Fused Rings.
AB  - Treatment of heterocyclic amines featuring fused rings of [1,2,4]triazolo[4,3
      b][1,2,4,5]tetrazine with fuming HNO3 /P2 O5 leads to six fully characterized
      explosives through multiple nitration and reduction or oxidation mechanism. Thus,
      4-nitro-N-(3-nitro[1,2,4]triazolo[4,3-b][1,2,4,5]tetrazin-6-yl)-1,2,5-oxadiazol-3
      amine (3 b, TTDNF) showed high performance (D=9180 m s-1 , P=36.7 GPa) and low
      impact sensitivity (IS>40 J) while N-([1,2,4]triazolo[4,3-b][1,2,4,5]tetrazin-6
      yl)-3-nitro-1,2,4-oxadiazol-5-amine (4 a, TTNOA) exhibited a potential cast
      explosive component with low melting point at 88.2  degrees C and high onset
      decomposition temperature at 226.2  degrees C.

PMID- 30277024
TI  - Body Composition Percentiles in Urban South Indian Children and Adolescents.
AB  - OBJECTIVE: This study aimed to generate age- and sex-specific percentiles for
      body composition indices in children and to assess the variability in these
      indices, in relation to BMI. METHODS: Anthropometry and body fat were measured
      with the BOD POD (Cosmed; Rome, Italy) in 9,702 children from Bangalore, India.
      Smoothed percentile curves using the lambda-mu-sigma method were obtained for
      BMI, fat-free mass index (FFMI), fat mass index (FMI), and body fat percentage (%
      BF). RESULTS: Percentile curves for % BF and FMI in boys increased from 6 to 12
      years and declined from 13 years on, while in girls, it increased until 15 years.
      The FFMI percentile curves increased with age in both sexes. The mean FMI
      declined from 12 years on in boys, corresponding to a large increase in FFMI from
      that age, while in girls, both FMI and FFMI continued to increase. The 75th
      percentile of % BF and FMI had greater sensitivity to identify children with
      obesity. CONCLUSIONS: This study developed smoothed percentile curves for body
      composition in Indian children and suggests FMI and FFMI as good indicators of
      growth in children.

PMID- 30277023
TI  - Prostate cancer survivors: Risk and mortality in second primary cancers.
AB  - To assess etiological and clinical consequences of second primary cancers (SPCs)
      in prostate cancer (PC) patients, we followed newly diagnosed patients to
      identify men who were diagnosed with a SPC and recorded their causes of death. We
      used the Swedish Family-Cancer Database to assess relative risks (RRs) and causes
      of death in SPCs until the year 2015 in patients with a PC diagnosis between 2001
      and 2010. Among a total of 4.26 million men, 76 614 were diagnosed with PC at the
      median age of 71 years. Among them, 8659 (11.3%) received a subsequent diagnosis
      of SPC after a median follow-up of 4 years. The most common SPCs were colorectal,
      skin, bladder, and lung cancers, melanoma, and non-Hodgkin lymphoma. The ranking
      was almost identical with first cancers among elderly men in Sweden. The RR for
      SPCs in prostate-specific antigen-detected PC was approximately equal to RR in
      other PC. Mortality patterns of PC patients were distinct depending on the
      presence or absence of SPC. Among patients with SPC, 47.8% died as a result of
      the corresponding SPC, followed by other causes (22.2%) and PC (18.1%). For
      patients without SPC, PC and non-neoplastic causes almost matched each other as
      the main causes of death (48.5% and 47.8%). The results suggest that SPCs appear
      autonomous from primary PC and reflect incidence and mortality of first cancers
      in general. SPC was the most common cause of death in patients with SPC; close to
      half of the patients died due to SPC. For improved survival in PC patients,
      prevention and early detection of SPCs would be important, and the present
      results suggest that risk factors for SPC in PC are the same as those for first
      cancer in general.

PMID- 30277025
TI  - Treating Obesity Seriously in Mexico: Realizing, Much Too Late, Action Must Be
      Immediate.

PMID- 30277026
TI  - Associations of Maternal Weight Status Before, During, and After Pregnancy with
      Inflammatory Markers in Breast Milk.

PMID- 30277028
TI  - What Will It Take for Mexico to Bend the Curve?

PMID- 30277027
TI  - Habitual Sleep Measures are Associated with Overall Body Fat, and not
      Specifically with Visceral Fat, in Men and Women.
AB  - OBJECTIVE: This study aimed to investigate the associations of sleep duration and
      sleep quality with visceral adipose tissue (VAT) in middle-aged individuals.
      METHODS: In this cross-sectional analysis of baseline measurements of the
      Netherlands Epidemiology of Obesity (NEO) study, participants underwent
      anthropometry and completed the Pittsburgh Sleep Quality Index (PSQI) for
      assessing short sleep duration (as sex-specific age-adjusted percentiles) and
      poor quality (PSQI > 5). VAT was assessed by magnetic resonance imaging in a
      random subgroup. We performed linear regression analyses to examine associations
      of short sleep and poor sleep with measures of body fat, adjusted for
      confounding, including total body fat in models with VAT. RESULTS: A total of
      5,094 participants (52% women; mean age of 56 [SD 6] years), 1,947 of whom had
      VAT measurements, were analyzed. The difference in VAT between poor sleep (PSQI >
      5) and good sleep (PSQI <= 5) was 7.2cm2 (95% CI: 1.2-13.8) in women and 16.1cm2
      (95% CI: 6.2-26.0) in men. These differences attenuated toward the null after the
      adjustment for total body fat. Similar patterns of associations were observed for
      short sleep (lowest 10% compared with median 60%). CONCLUSIONS: Our results
      suggest that measures of sleep are not specifically associated with a higher
      amount of VAT.

PMID- 30277029
TI  - Anthropometry Versus Imaging for Prediction of Inflammation Among Hispanic Girls.
AB  - OBJECTIVE: This study aimed to compare total and regional estimates of body
      composition, by direct and indirect techniques, for the optimal prediction of C
      reactive protein (CRP) among young (aged 9-12 years) Hispanic girls (N = 232).
      METHODS: Standard anthropometric techniques were used to measure height, weight,
      and waist circumference. Dual-energy X-ray absorptiometry (DXA) and peripheral
      quantitative computed tomography (pQCT) assessed body composition. Fasting serum
      CRP was measured by the AU5812 Clinical Chemistry Analyzer (Beckman Coulter,
      Brea, California). Associations between each total and regional body composition
      parameter and CRP were tested using linear regression (log-transformed,
      continuous CRP) and ordinal logistic regression (CRP < 1.0, >= 1.0-2.9, and >=
      3.0 mg/L), controlling for maturation, dietary energy, physical activity, and
      medications. RESULTS: All measures of total and regional body fat were positively
      associated with CRP (P < 0.0001) except for intermuscular fat by pQCT. There were
      no clinically relevant differences in their association with CRP between
      anthropometric (BMI; waist circumference) and DXA-derived (total fat and regional
      fat: trunk, gynoid, android fat, leg) measures of fat. CONCLUSIONS: Measurement
      of body habitus in Hispanic girls, by multiple commonly available means, predicts
      CRP equally well.

PMID- 30277030
TI  - Dissemination of the Look AHEAD Intensive Lifestyle Intervention in the United
      States Military: A Randomized Controlled Trial.
AB  - OBJECTIVE: The purpose of this study, "Fit Blue," was to compare a translation of
      the Look AHEAD (Action for Heath in Diabetes) intensive lifestyle intervention
      with a self-paced version of the same intervention among active duty military
      personnel. METHODS: Active duty military personnel (N = 248; 49% male, 34% racial
      minority) with overweight or obesity were randomized to 12-month distance-based
      (i.e., phone and email) parallel programs, counselor-initiated (CI) condition or
      self-paced (SP) condition, from 2014 to 2016. Trained lay interventionists were
      retired military personnel or had extensive familiarity with the military.
      RESULTS: The CI condition had greater weight loss at 4 months (CI: mean +/- SD = 
      3.2 +/- 3.4 kg; SP: -0.6 +/- 2.9 kg; P < 0.0001) and at 12 months (CI: mean +/-
      SD = -1.9 +/- 4.1 kg; SP: -0.1 +/- 3.8 kg; P < 0.001). Participants in the CI
      condition also had a greater percent weight loss at both 4 months (CI: 3.5% +/-
      3.8, SP: 0.6% +/- 3.1; P < 0.0001) and 12 months (CI: 2.1% +/- 4.7, SP: 0.0% +/-
      4.0; P < 0.001). In addition, a greater proportion of CI participants lost 5% or
      more at 4 months (CI: 29.8%, SP: 10.5%; P < 0.001) and at 12 months (CI: 29.5%,
      SP: 15.6%; P < 0.05). CONCLUSIONS: The CI behavioral weight loss intervention
      translated from Look AHEAD was well received and is a promising approach for
      managing weight in an active duty military population.

PMID- 30277031
TI  - Changes in the Perceptions of Self-weighing Across Time in a Behavioral Weight
      Loss Intervention.
AB  - OBJECTIVE: Changes in beliefs about self-weighing were examined across time in a
      behavioral weight loss intervention. METHODS: Active duty military personnel (n =
      248) enrolled in a 12-month counselor-initiated or self-paced intervention based
      on the Look AHEAD (Action for Health in Diabetes) Intensive Lifestyle
      Intervention. Using an electronic scale, participants were asked to self-weigh
      daily. Self-weighing perceptions were compared from baseline to 4 months (weight
      loss phase), from 4 months to 12 months (weight maintenance phase), and from
      baseline to 12 months (full intervention), as well as across time by behavioral
      and demographic characteristics. RESULTS: Overall, participants perceived self
      weighing as more helpful and positive, less frustrating, and making them less
      self-conscious after the weight loss phase. After weight maintenance, individuals
      believed self-weighing was less helpful and positive, more frustrating and
      anxiety provoking, and making them more self-conscious. However, after the
      intervention, participants still viewed self-weighing as more helpful and
      positive and less frustrating than at baseline. Weight change, self-weighing
      behavior prior to the intervention, and intervention condition were associated
      with perception change. Controlling for these influencing factors, differences in
      gender, BMI, age, ethnicity, and race were observed in how beliefs changed across
      time. CONCLUSIONS: Results suggest engaging in a weight loss intervention
      promoting daily self-weighing increases positive and decreases negative beliefs
      about self-weighing.

PMID- 30277033
TI  - Quantitative analysis of liver tumors at different stages using microscopic
      hyperspectral imaging technology.
AB  - Liver cancer has one of the highest rates of human morbidity and mortality.
      However, in terms of pathology, liver cancer is traditionally clinically
      diagnosed based on observation of microscopic images of pathological liver
      sections. This paper investigates in vitro samples of rat models of bile duct
      carcinoma and presents a quantitative analysis method based on microscopic
      hyperspectral imaging technology to evaluate liver cancers at different stages.
      The example-based feature extraction method used in this paper mainly includes
      two algorithms: a morphological watershed algorithm is applied to find object and
      segment pathological components of pathological liver sections at different
      stages, and a support vector machine algorithm is implemented for liver tumor
      classification. Majority/minority analysis is utilized as the postclassification
      tool to eliminate small plaques from the preliminary classification results.
      Then, pseudocolor synthesis in RGB color space is used to produce the final
      results. The experimental results show that this method can effectively calculate
      the percent tumor areas in liver biopsies at different time points, that is,
      3.338%, 11.952%, 15.125%, and 23.375% at 8, 12, 16, and 20 weeks, respectively.
      Notably, through tracking analysis, the processed results of 8-week images showed
      the possibility for early diagnosis of the liver tumor.

PMID- 30277032
TI  - Structured polarized light microscopy for collagen fiber structure and
      orientation quantification in thick ocular tissues.
AB  - Collagen is a major constituent of the eye and understanding its architecture and
      biomechanics is critical to preserve and restore vision. We, recently,
      demonstrated polarized light microscopy (PLM) as a powerful technique for
      measuring properties of the collagen fibers of the eye, such as spatial
      distribution and orientation. Our implementation of PLM, however, required
      sectioning the tissues for imaging using transmitted light. This is problematic
      because it limits analysis to thin sections. This is not only slow, but precludes
      study of dynamic events such as pressure-induced deformations, which are central
      to the role of collagen. We introduce structured polarized light microscopy
      (SPLM), an imaging technique that combines structured light illumination with PLM
      to allow imaging and measurement of collagen fiber properties in thick ocular
      tissues. Using pig and sheep eyes, we show that SPLM rejects diffuse background
      light effectively in thick tissues, significantly enhancing visualization of
      optic nerve head (ONH) structures, such as the lamina cribrosa, and improving the
      accuracy of the collagen fiber orientation measurements. Further, we demonstrate
      the integration of SPLM with an inflation device to enable direct visualization,
      deformation tracking, and quantification of collagen fibers in ONHs while under
      controlled pressure.

PMID- 30277035
TI  - ?

PMID- 30277036
TI  - ?

PMID- 30277034
TI  - Truth and consensus.

PMID- 30277037
TI  - ?

PMID- 30277039
TI  - ?

PMID- 30277038
TI  - Disease burden in Norway in 2016.
AB  - BAKGRUNN: For a kunne mote helseutfordringer i befolkningen trenger vi oversikt
      over befolkningens helsetilstand. I Norge har vi tradisjonelt hatt god oversikt
      over dodsarsaker, men vi vet mindre om byrden fra tilstander som medforer
      sykelighet, sakalt ikke-dodelig helsetap. Vart mal var a beskrive den totale
      sykdomsbyrden i Norge i 2016, utviklingen de siste ti arene samt
      kjonnsforskjeller i sykdomsbyrde. MATERIALE OG METODE: Vi brukte resultater fra
      det globale sykdomsbyrdeprosjektet Global Burden of Diseases, Injuries and Risk
      Factors Study (GBD), som kvantifiserer ikke-dodelig helsetap slik at det kan
      males pa samme skala som dodelighet i form av tapte levear. Summen av tapte
      levear og ikke-dodelig helsetap gir sykdomsbyrdemalet helsetapsjusterte levear
      (DALY). RESULTATER: Ikke-smittsomme sykdommer som hjerte- og karsykdom, kreft,
      kronisk obstruktiv lungesykdom og demens var viktige arsaker til tapte levear hos
      begge kjonn i Norge i 2016. Ikke-dodelig helsetap utgjorde 52 % av sykdomsbyrden
      malt i helsetapsjusterte levear. Spesielt muskel- og skjelettsykdommer, psykiske
      lidelser og ruslidelser var viktige. De siste ti arene har sykdomsbyrden (i
      aldersjusterte rater) sunket for mange tilstander som medforer tapte levear, men
      ikke for tilstander som gir ikke-dodelig helsetap. FORTOLKNING: Ikke-dodelig
      helsetap utgjor en stor og okende andel av sykdomsbyrden i den norske
      befolkningen, noe som vil gi nye utfordringer for helsevesenet.

PMID- 30277040
TI  - Group supervision - an unmet need among specialty registrars.

PMID- 30277041
TI  - ?

PMID- 30277042
TI  - ?

PMID- 30277043
TI  - ?

PMID- 30277044
TI  - ?

PMID- 30277045
TI  - ?

PMID- 30277046
TI  - ?

PMID- 30277047
TI  - Has a 'shaken baby' always been shaken?

PMID- 30277048
TI  - ?
AB  - BACKGROUND: The withdrawal of digitoxin and subsequent substitution with digoxin
      around 2012 may have led to an increased health risk for patients. The aim of
      this study was to follow individual patients during the switch. MATERIAL AND
      METHOD: Serum concentrations of digitoxin and digoxin, measured at the Department
      of Clinical Pharmacology at St Olavs University Hospital in the period 1 January
      2011-31 December 2013 were reviewed. Patients who had switched from digitoxin to
      digoxin and whose serum concentrations of both drugs had been measured during
      this period were included. RESULTS: A total of 304 patients, 1686 samples and
      1858 serum concentration analyses were included in the study. Therapeutic serum
      concentrations were measured in 171 patients (56.3 %) before the switch and 176
      (57.9 %) after this had taken place. Altogether 108 patients (35.5 %) had
      therapeutic concentrations both before and after the change. For 58.9 % of the
      patients, the change resulted in a reduction in serum concentration of digitalis,
      calculated as digoxin equivalents. The proportion of patients with assumed
      supratherapeutic concentrations fell from 43.1 % to 33.9 %; however, the
      proportion of patients with toxic serum concentrations rose from 0.3 % to 3.0 %.
      INTERPRETATION: Although the switch led to a reduction in dose and serum
      concentration for many, a significant number of patients may have been put in
      harm's way.

PMID- 30277050
TI  - ?

PMID- 30277049
TI  - ?
AB  - Gastrointestinal stromal tumour (GIST) is a subtype of sarcoma that may occur in
      any part of the gastrointestinal system, most frequently in the stomach and small
      intestine. The most common symptoms are bleeding and abdominal pain. In this
      clinical review, we summarise the progress made with this condition and discuss
      the recommended diagnostics and treatment of GIST.

PMID- 30277051
TI  - A man in his twenties with dizziness, double vision and peripheral facial palsy.

PMID- 30277052
TI  - ?

PMID- 30277053
TI  - [Changes in Elemental and Isotopic Composition Accompanying Larval Growth and
      Metamorphosis of the Moor Frog].
AB  - A variety of early ontogenetic events of anuran species (growth, structural and
      biochemical diversification,metamorphosis) offers a unique opportunity to
      evaluate the effectiveness and application limits ofmass spectrometry method for
      the analysis of metabolic and transformation events in developing organisms.The
      dynamics of relative carbon and nitrogen contents and stable isotopes of these
      elements during larvaldevelopment in the period of metamorphosis climax and after
      its conclusion in moor frog specimens developingin their natural habitat and in
      vitro on a referent diet are traced. A decrease in C/N ratio and enrichmentof the
      tissues with heavy stable isotopes of carbon and nitrogen during embryonal and
      larval development(prior to the beginning of independent feeding) indicates the
      increase in the portion and variety of proteins,accompanied by consumption of
      yolk lipids. The relative nitrogen content increase and C/N ratio decreaseswith
      the growth and development of independently feeding tadpoles, which indicates
      surpassing increase ofthe portion of proteins in tissues. In growing tadpoles,
      the rates of tissue renewal in general and rates of proteinmetabolism in
      particular affect the kinetics of changes of tissue isotope composition, which
      approaches isotopecomposition of the consumed food. A decrease in S/N ratio in
      the bodies of metamorphs during masstissue decomposition is indicative of
      continuing reconstruction of larval organs and growth of anlage of
      definitiveorgans. Significant increase of C/N ratio and depletion of liver
      samples by heavy carbon isotopes areassociated with intensive synthesis and
      reservation of lipids within the organ. Strong enrichment of metamorphs'tissues
      with heavy nitrogen isotope indicates the substitution of ammoniotelic type of
      nitrogenmetabolism by urotelic type. Decrease in C/N ratio and enrichment of
      tissues by heavy carbon isotope maybe connected to intensive oxidation of lipids,
      which supports the growing energy costs of terrestrial underyearlings.Relative
      contents of heavy nitrogen isotope in the tissues of underyearlings does not
      change comparedto the tissues of metamorphs.

PMID- 30277054
TI  - [Efficiency of Cell Transplantation in Repair of Mouse Liver Damage].
AB  - The effectiveness of two transplantation methods of human hepatocellular
      carcinoma cells HepG2and allogeneic mesenchymal stromal cells of adipose tissue
      (AT MSCs) into mice was compared in order toselect the most effective for liver
      damage repair. Considerable advantage of cell transplantation into the
      spleencompared with intraperitoneal administration was shown. It is found that,
      under similar conditions of transplantation,AT MSCs are detected in liver tissue
      in smaller quantities than human hepatocellular carcinomacells HepG2; differences
      in cell localization of these types of cells in the liver are revealed. A
      tendency todecrease in the degree of fibrotic changes in liver tissue after
      transplantation of AT MSCs and to a greaterextent after transplantation of AT
      MSCs, pretreated with interleukin-6, was traced.

PMID- 30277055
TI  - Addressable TiO2 Nanotubes Functionalized Paper-Based Cyto-Sensor with
      Photocontrollable Switch for Highly-Efficient Evaluating Surface Protein
      Expressions of Cancer Cells.
AB  - Inspired by the well-known "Wheel of Fortune", a rotatable paper
      photocontrollable switch (RPPS) was designed to form an addressable paper-based
      photoelectrochemical (PEC) cyto-sensor for ultrasensitive detection of a cell
      surface protein. By simply rotating the RPPS, a light source can selectively
      activate the desired working zones of the cyto-sensor. To realize the high
      performance paper-based PEC cyto-sensor, a cascaded photoactive interface
      consisting of neat TiO2 nanotubes arrays, Pt nanoparticles (NPs), and nitrogen
      carbon dots was introduced into paper fibers, gaining signal-on PEC state (NTPP
      for short). Then the NTPP fixed with a hairpin probe H1 allowed the hybridization
      chain reaction (HCR) to happen with CuS NPs-labeled hairpin probe H2 by the free
      primer strand (PS) triggering; hence, the CuS NPs as the emulative sensitizers
      were introduced onto the NTPP with the photocurrent intensity decrement for
      signal-off PEC state. During this process, the PS carefully designed with
      specific sequences can recognize the target strand (TS) of MCF-7 cells and
      stimulate HCR by its trigger zone. The presence of MCF-7 cells destroyed the
      interaction between PS and ZnFe2O4 functionalized TS, causing the PS release from
      the mixture of PS and TS under the help of a magnet. Then, the released PS,
      acting as a primer probe, realized ultrasensitive detection of a cell-surface
      protein. On the basis of this novel protocol, multiple-signal amplification was
      skillfully imported into the addressable paper PEC chip, resulting in
      ultrasensitive quantification of carcinoembryonic antigen in the surface of MCF-7
      cells. Given the fascinating analytical performances of the developed cyto
      sensor, ultralow expression of antigens for MCF-7, A549, and PC 3 cells was
      discriminated effectively.

PMID- 30277056
TI  - Insight into the Mechanism of the Ionic Conductivity for Ln-Doped Ceria (Ln = La,
      Pr, Nd, Pm, Sm, Gd, Tb, Dy, Ho, Er, and Tm) through First-Principles Calculation.
AB  - Oxygen vacancy (VO) formation energy and its migration barrier are two
      determining factors for the effectiveness of solid electrolytes (SEs) in solid
      oxide fuel cells (SOFCs). In this work, a series of aliovalent rare-earth-doped
      ceria (Ln xCe1- xO2-delta, Ln = lanthanides) compounds serving as SEs are
      comprehensively and comparatively calculated, through which the determinant
      factors for oxygen vacancy formations and their migration activity are figured
      out at an atomistic level via the first-principles calculations with the
      consideration of electronic correlations. Initially, it is found that the oxygen
      vacancy formation energies of the Ln-doped ceria are largely reduced in contrast
      to the undoped ceria (CeO2-delta), which obviously agree with the literature.
      Then, the migration activity of an oxygen vacancy in Ln xCe1- xO2-delta is
      closely correlated to the association energies of Ln-VO, in which the different
      4f5d bonding properties for different Ln ions should be taken into account.
      Additionally, the analysis of charge difference gradient (CDG) is revealed to be
      the intrinsic driving force for oxygen vacancy migration. We hope that our
      investigation provides a microscopic insight into the oxygen vacancy defect
      physics, and it is also a benefit for the design of more advanced relevant
      functional materials.

PMID- 30277057
TI  - Live Monitoring of Microenvironmental pH Based on Extracellular Acidosis around
      Cancer Cells with Cell-Coupled Gate Ion-Sensitive Field-Effect Transistor.
AB  - We demonstrated the live monitoring of cellular respiration using an ion
      sensitive field-effect transistor (ISFET), focusing on different types of living
      cells, namely cancer and normal cells. In particular, we realized the label-free,
      real-time, and noninvasive monitoring of microenvironmental pH behavior based on
      extracellular acidosis around cancer cells in the long term and in situ. The
      change in interfacial pH (DeltapHint), which was analyzed based on the change in
      interfacial potential (Delta Vout) at the cell/gate nanogap interface gradually
      decreased for every cell-based ISFET. Moreover, the DeltapHint for cancer cells
      shifted by a factor of 5 to 6, which was larger than that for normal cells. This
      is because cancer cells cause dysbolism and are activated, thereby suppressing
      oxidative phosphorylation in mitochondria so as not to induce their apoptosis.
      Therefore, cancer cellular respiration proceeds via the glycolysis pathway,
      through which lactic acid is eventually released. Additionally, the pH
      sensitivity of the ISFET device was maintained even when the device was immersed
      into a cell culture medium for 24 h and 1 w; thus, the effect of nonspecific
      adsorption of proteins contained in the medium on the pH sensitivity of the ISFET
      device was negligible in the live monitoring of cellular respiration.

PMID- 30277058
TI  - Chemical Sensing in Real Time with Plants Using a Webcam.
AB  - It has been established that plants can smell and respond to chemicals in order
      to adapt to and survive in a changing chemical environment. Here we show that a
      plant responds to chemicals in air, and the response can be detected rapidly to
      allow tracking of air pollution in real time. We demonstrate this capability by
      detecting subtle color and shape changes in the leaves of mosses upon exposure to
      sulfur dioxide in air with a simple webcam and an imaging-processing algorithm.
      The leaves of mosses consist of a monolayer of cells, providing a large surface
      to-volume ratio for highly sensitive chemical sensing. The plant sensor responds
      linearly to sulfur dioxide within a wide concentration range (0-180 ppm), and it
      can tolerate humidity variation (15-85% relative humidity) and chemical
      interference and regenerate itself. We envision that plants can help alert
      chemical exposure danger as a part of our living environment using low-cost CMOS
      imagers, and their chemical-sensing capabilities may be further improved with
      genetic engineering.

PMID- 30277059
TI  - Sub-2 V, Transfer-Stamped Organic/Inorganic Complementary Inverters Based on
      Electrolyte-Gated Transistors.
AB  - Organic/inorganic hybrid complementary inverters operating at low voltages (1 V
      or less) were fabricated by transfer-stamping organic p-type poly(3
      hexylthiophene) (P3HT) and inorganic n-type zinc oxide (ZnO) electrolyte-gated
      transistors (EGTs). A semicrystalline homopolymer-based gel electrolyte, or an
      ionogel, was also transfer-stamped on the semiconductors for use as a high
      capacitance gate insulator. For the ionogel stamping, the thermoreversible
      crystallization of phase-separated homopolymer crystals, which act as network
      cross-links, was employed to improve the contact between the gel and the
      semiconductor channel. The homopolymer ionogel-gated P3HT transistor exhibited a
      high hole mobility of 2.81 cm2/(V s), and the ionogel-gated n-type ZnO
      transistors also showed a high electron mobility of 2.06 cm2/(V s). The transfer
      stamped hybrid complementary inverter based on the P3HT and ZnO EGTs showed a low
      voltage operation with appropriate inversion characteristics including a high
      voltage gain of ~18. These results demonstrate that the transfer-stamping
      strategy provides a facile and reliable processing route for fabricating
      electrolyte-gated transistors and logic circuits.

PMID- 30277060
TI  - Stabilization and Reversal of Skyrmion Lattice in Ta/CoFeB/MgO Multilayers.
AB  - Recently, magnetic skyrmion has attracted much attention due to its potential
      application in racetrack memory and other nanodevices. In bulk chiral magnets
      with non-centrosymmetric crystal structures, skyrmion lattice phase has been
      extensively observed. However, in film or multilayers with interfacial
      Dzyaloshinskii-Moriya interaction, individual skyrmion is often observed. Here,
      we report a short-ordered skyrmion lattice observed in [Ta(5.0 nm)/CoFeB(1.5
      nm)/MgO(1.0 nm)]15 multilayer in a remnant state. The structure, stabilization,
      and reversal of these skyrmions are discussed. Applying a slightly tilted in
      plane magnetic field caused reversal of the skyrmion lattice. This reversal came
      from disappearance of skyrmions and nucleation of new skyrmions in the
      interstitial regions of the lattice. Also, we investigated how the skyrmion
      lattice depended on the CoFeB thickness. Our findings provide a pathway to
      stabilize and reverse the skyrmions in multilayers films.

PMID- 30277061
TI  - Bendable InGaN Light-Emitting Nanomembranes with Tunable Emission Wavelength.
AB  - The integration of light-emitting diodes (LEDs) into the flexible devices has
      exhibited a great potential in the next-generation consumer electronics. In this
      study, we have demonstrated an exfoliated InGaN nanomembrane LED (NM-LED)
      separated from a GaN/sapphire substrate through an electrochemically wet etching
      process. The peak wavelengths blue-shifted phenomenon of the photoluminescence
      (PL) and the electroluminescence spectra were observed on the free-standing NM
      LED compared to the nontreated LED with the same structure, which can be ascribed
      to the partial strain relaxation of the LED structure confirmed by the Raman
      spectra and the X-ray diffraction curves. A small divergent angle of the PL
      emission light has also been observed on the NM-LED. Moreover, the peak emission
      wavelength of this NM-LED can be even modulated from a red shift (521.7 nm) to a
      blue shift (500.4 nm) compared with that of the flat state (509.4 nm) while being
      curved convexly from top p-GaN:Mg side to bottom n-GaN:Si side. Our study
      provides an elegant way to develop a bendable light source with variable emission
      wavelengths through the mechanical deformation method.

PMID- 30277062
TI  - Satellite-based land-use regression for continental-scale long-term ambient PM2.5
      exposure assessment in Australia.
AB  - Australia has relatively diverse sources and low concentrations of ambient fine
      particulate matter (<2.5 um, PM2.5). Few comparable regions are available to
      evaluate the utility of continental-scale land-use regression (LUR) models
      including global geophysical estimates of PM2.5, derived by relating satellite
      observed aerosol optical depth to ground-level PM2.5 ('SAT-PM2.5'). We aimed to
      determine the validity of such satellite-based LUR models for PM2.5 in Australia.
      We used global SAT-PM2.5 estimates (~10 km grid) and local land-use predictors to
      develop four LUR models for year-2015 (two satellite-based, two non-satellite
      based). We evaluated model performance at 51 independent monitoring sites not
      used for model development. An LUR model that included the SAT-PM2.5 predictor
      variable (and six others) explained the most spatial variability in PM2.5
      (adjusted R2 = 0.63, RMSE (ug/m3 [%]): 0.96 [14%]). Performance decreased
      modestly when evaluated (evaluation R2 = 0.52, RMSE: 1.15 [16%]). The evaluation
      R2 of the SAT-PM2.5 estimate alone was 0.26 (RMSE: 3.97 [56%]). SAT-PM2.5
      estimates improved LUR model performance, while local land-use predictors
      increased the utility of global SAT-PM2.5 estimates, including enhanced
      characterization of within-city gradients. Our findings support the validity of
      continental-scale satellite-based LUR modeling for PM2.5 exposure assessment in
      Australia.

PMID- 30277063
TI  - Several Orders of Magnitude Difference in Charge-Transfer Kinetics Induced by
      Localized Trapped Charges on Mixed-Halide Perovskites.
AB  - Partial halide substitution in organolead halide perovskites MAPbX3 (MA =
      CH3NH3+, X = Cl-, Br-, or I-) leads to semiconductor heterostructures with
      precisely tuned band-gap energies, which facilitates efficient charge extraction
      or separation for high-performance solar cells and optoelectronic devices. In
      this study, partially iodide-substituted MAPbBr3 perovskites were prepared
      through a halide-exchange reaction in the liquid phase, and in situ space- and
      time-resolved photoluminescence profiles were acquired by means of confocal
      microscopy. The rates of charge transfer from the bulk MAPbBr3 to the surface
      MAPbBr3- xI x domains, which are widely distributed over a single crystal, were
      found to greatly depend on the excitation-power density. In particular, an
      abnormally slow charge-transfer process, lasting a few nanoseconds, was observed
      at higher excitation density. To explain the dependence of this rate on the
      excitation density, and its correlation with the charge-trapping rate in the bulk
      MAPbBr3, we propose a plausible mechanism in which trap filling associated with
      surface-trapped holes induces band bending within the space charge region. This
      band bending modulates carrier dynamics near the surface, thereby leading to
      efficient charge extraction from the bulk. To validate the mechanism, the carrier
      dynamics was numerically simulated using a diffusion model that includes the
      effect of the localized electric field. Our findings provide significantly deeper
      insight into the carrier dynamics within heterostructured perovskites with
      nanoscale heterogeneities, and a robust route for manipulating the photogenerated
      charges in various types of perovskite devices.

PMID- 30277064
TI  - Two-Dimensional WSe2/MoS2 p-n Heterojunction-Based Transparent Photovoltaic Cell
      and Its Performance Enhancement by Fluoropolymer Passivation.
AB  - As a means to overcome the limitation of installation space and to promote the
      utilization of the solar cell in various applications, a transparent thin-film
      solar cell has been studied by many researchers. To achieve a transparent solar
      cell, the choice of materials which are transparent enough and showing the
      photovoltaic property at the same time is the key. Here, we suggest a two
      dimensional (2D) p-n heterojunction of WSe2/MoS2 and an indium tin oxide
      electrode to fabricate a transparent thin-film photovoltaic cell. Because of
      advantages that 2D materials possess, a highly transparent (~80%) solar cell with
      considerable efficiency was achieved. Furthermore, by introducing a transparent
      passivation layer composed of a fluoropolymer, the photovoltaic performance was
      much improved. With the passivation layer, our WSe2/MoS2 transparent photovoltaic
      cell reached an efficiency of ~10%. A comparison of photovoltaic parameters
      before and after applying passivation and analysis on the origin of such
      differences are also discussed. To the best of our knowledge, this is the first
      report to fabricate a 2D material-based fully transparent photovoltaic device.
      Our result exhibits a great potential of the van der Waals p-n heterojunction of
      2D semiconductors to be utilized for an active layer of a highly transparent and
      lightweight thin-film solar cell.

PMID- 30277065
TI  - Detection of Lysosome by a Fluorescent Heterocycle: Development of Fused Pyrido
      Imidazo-Indole Framework via Cu-Catalyzed Tandem N-Arylation.
AB  - Fluorescent active small molecules for organelle-specific bioimaging are in great
      demand. We synthesized 20 different pyrido-imidazo-indole fused heterocycles (6-5
      5-6 ring) via copper catalyzed tandem N-arylation reaction in moderate to good
      yields. Due to decent fluorescent property, lysosome-directing moieties were
      attached on two of these heterocycles. Delightfully, those molecules tracked
      lysosome with bright blue fluorescence and colocalized with a known lysosome
      marker (Lysotracker Red) in human/murine cells. Therefore, it may be considered
      as a rapid (10 min) lysosome staining probe.

PMID- 30277066
TI  - Computational Design of Synthetic Enzymes.
AB  - We review the standard model for de novo computational design of enzymes, which
      primarily focuses on the development of an active-site geometry, composed of
      protein functional groups in orientations optimized to stabilize the transition
      state, for a novel chemical reaction not found in nature. Its emphasis is placed
      on the structure and energetics of the active site embedded in an accommodating
      protein that serves as a physical support that shields the reaction chemistry
      from solvent, which is typically improved upon by laboratory-directed evolution.
      We also provide a review of design strategies that move beyond the standard
      model, by placing more emphasis on the designed enzyme as a whole catalytic
      construct. Starting with complete de novo enzyme design examples, we consider
      additional design factors such as entropy of individual residues, correlated
      motion between side chains (mutual information), dynamical correlations of the
      enzyme motions that could aid the reaction, reorganization energy, and electric
      fields as ways to exploit the entire protein scaffold to improve upon the
      catalytic rate, thereby providing directed evolution with better starting
      sequences for increasing biocatalytic performance.

PMID- 30277067
TI  - Poly(nickel-ethylenetetrathiolate) and Its Analogs: Theoretical Prediction of
      High-Performance Doping-Free Thermoelectric Polymers.
AB  - It is generally deemed that doping is a must for polymeric materials to achieve
      their high thermoelectric performance. We herein present the first report that
      intrinsically metallic behaviors and high-performance thermoelectric power
      factors can coexist within doping-free linear-backbone conducting polymers,
      poly(nickel-ethylenetetrathiolate) and its analogs. On the basis of density
      functional calculations, we have corroborated that four crystalline pi- d
      conjugated transition-metal coordination polymers, including poly(Ni-C2S4),
      poly(Ni-C2Se4), poly(Pd-C2S4) and poly(Pt-C2S4) exhibit intrinsically metallic
      behavior arising from the formation of dense intermolecular interaction networks
      between sulfur/selenium atoms. They show moderate carrier concentrations (1019
      1021 cm-3) and decent conductivities (103-104 S cm-1), among which, poly(Ni
      C2S4), poly(Ni-C2Se4) and poly(Pd-C2S4) possess high power factors (~103 MUW m-1
      K-2).

PMID- 30277068
TI  - Enzymatic On-Resin Peptide Cleavage and in Situ Cyclization One-Pot Strategy for
      the Synthesis of Cyclopeptide and Cyclotide.
AB  - A one-pot strategy combining sortase A mediated on-resin peptide cleavage and in
      situ cyclization was developed for the synthesis of cyclic peptides. This
      strategy was applied to synthesize head-to-tail cyclic antibacterial bovine
      lactoferricin peptide LFcinB20-35 in a yield of 67%. The one-pot strategy was
      compatible with an oxidative folding reaction, and complex cyclotides containing
      one or two disulfide bonds, such as sunflower trypsin inhibitors-1 and alpha
      conotoxin MII, were successfully synthesized in one pot in a yield of 77% and
      61%, respectively.

PMID- 30277069
TI  - Realization of Thermally Stimulated Delayed Phosphorescence in Arylgold(III)
      Complexes and Efficient Gold(III) Based Blue-Emitting Organic Light-Emitting
      Devices.
AB  - To address and overcome the difficulties associated with the increased reactivity
      and susceptibility of blue emitters to deactivation pathways arising from the
      high-lying triplet excited states, we have successfully demonstrated an
      innovative strategy of harvesting triplet emission via the "thermally stimulated
      delayed phosphorescence" mechanism, where thermal up-conversion of excitons from
      the lower-energy triplet excited states (T1) to higher-energy triplet excited
      states (T1') are observed to generate blue emission. The lower-lying T1 excited
      state could serve as a mediator to populate the emissive T1' state by up
      conversion via reverse internal conversion, which could enhance the
      photoluminescence quantum yield by over 20-folds. Organic light-emitting devices
      with respectable external quantum efficiencies of up to 7.7% and sky-blue
      emission with CIE coordinates of (0.17, 0.37) have been realized. The operational
      stability for the device based on complex 1 has also been explored, and the
      device is found to show fairly respectable lifetime. This work opens up a new
      avenue to the design and synthesis of blue phosphorescent emitters.

PMID- 30277070
TI  - Polymer Nanowires with Highly Precise Internal Morphology and Topography.
AB  - The construction of precise soft matter nanostructures in solution presents a
      challenge. A key focus remains on the rational design of functionalities to
      achieve the high morphological complexity typically found in biological systems.
      Advances in controlled polymerizations and self-assembly increasingly allow
      approaches toward complex hierarchical nanomaterials. By combining tailor-made
      cylindrical polymer brushes, block copolymers and interpolyelectrolyte
      complexation-driven self-assembly, we demonstrate a facile construction of
      uniformly compartmentalized and topographically structured polymeric nanowires in
      aqueous media. The approach offers a modular avenue in programming the internal
      morphology of polymer nanowires by varying the block copolymer composition and
      topology.

PMID- 30277072
TI  - Uncovering the Spatiotemporal Dynamics of Urban Infrastructure Development: A
      High Spatial Resolution Material Stock and Flow Analysis.
AB  - Understanding the complexity and sustainability of infrastructure development is
      crucial for reconciling economic growth, human well-being, and environmental
      conservation. However, previous studies on infrastructure's material metabolism
      were mainly conducted on a global or national scale, due largely to lack of more
      spatially refined data, and thus could not reveal the spatial patterns and
      dynamics on a city scale. Here, we integrated material flow analysis (MFA) and
      geographical information system (GIS) data to uncover the spatiotemporal patterns
      of the material stocks and flows accompanying the infrastructure development at a
      high spatial resolution for the case of Shanghai, China. From 1980 to 2010,
      material stocks and waste output flows of Shanghai's infrastructure system
      exhibited a significant increase from 83 to 561 million metric tons (Mt) and from
      2 to 17 Mt, respectively. Input flows peaked in 2005 because of the economic
      slowdown and stepped-up policies to cool the housing market. Spatially, the
      center and peri-urban areas were the largest container of material stocks and
      biggest generator of demolition waste, while suburban areas absorbed 58%-76% of
      material inputs. Plans to make the city more compact will enhance the service
      capacity of stocks but may also increase the use of more energy and emissions
      intensive construction materials (e.g., steel). Prolonging the service lifetime
      of infrastructure through proper management and increasing the recycling and
      reuse rate of demolition waste are also identified as highly efficient
      strategies.

PMID- 30277071
TI  - Nanostructured Metal Hydrides for Hydrogen Storage.
AB  - Knowledge and foundational understanding of phenomena associated with the
      behavior of materials at the nanoscale is one of the key scientific challenges
      toward a sustainable energy future. Size reduction from bulk to the nanoscale
      leads to a variety of exciting and anomalous phenomena due to enhanced surface-to
      volume ratio, reduced transport length, and tunable nanointerfaces.
      Nanostructured metal hydrides are an important class of materials with
      significant potential for energy storage applications. Hydrogen storage in
      nanoscale metal hydrides has been recognized as a potentially transformative
      technology, and the field is now growing steadily due to the ability to tune the
      material properties more independently and drastically compared to those of their
      bulk counterparts. The numerous advantages of nanostructured metal hydrides
      compared to bulk include improved reversibility, altered heats of hydrogen
      absorption/desorption, nanointerfacial reaction pathways with faster rates, and
      new surface states capable of activating chemical bonds. This review aims to
      summarize the progress to date in the area of nanostructured metal hydrides and
      intends to understand and explain the underpinnings of the innovative concepts
      and strategies developed over the past decade to tune the thermodynamics and
      kinetics of hydrogen storage reactions. These recent achievements have the
      potential to propel further the prospects of tuning the hydride properties at
      nanoscale, with several promising directions and strategies that could lead to
      the next generation of solid-state materials for hydrogen storage applications.

PMID- 30277073
TI  - Temperature-Controlled Thiation of alpha-Cyano-beta-Alkynyl Carbonyl Derivatives
      for De Novo Synthesis of 2-Aminothiophenes and Thieno[2,3- c]isothiazoles.
AB  - Making use of temperature-controlled thiation as a key operation, a simple route
      to 2-aminothiophenes or thieno[2,3- c]isothiazoles has been newly developed
      wherein the 2-aminothiophene nucleus was formed through an initial formation of
      thioamide followed by a 5-exo-dig addition to the tethered alkyne; however, under
      harsher thermal conditions, excess sulfur-transferring reagents enabled further
      oxidative thiation to generate the corresponding thieno[2,3- c]isothiazoles.

PMID- 30277074
TI  - Brightness Enhancement in Pulsed-Operated Perovskite Light-Emitting Transistors.
AB  - Perovskite light-emitting field-effect transistors (PeLEFETs) provide a versatile
      device architecture to control transport and electroluminescence properties of
      hybrid perovskites, enabling injection of high charge carrier density and spatial
      control of the radiative recombination zone. Ionic screening and organic cation
      polarization effects typical of metal-halide perovskites, however, critically
      affect PeLEFET efficiency and reliability. In this work, we demonstrate a new
      device operation mode based on high-frequency modulation of the applied voltages,
      which allows significant reduction of ionic drift/screening in methylammonium
      lead iodide light-emitting transistors. In optimized top contact PeLEFETs, AC
      operation results in brighter and more uniform electroluminescence compared to DC
      driven devices, whereas high-frequency modulation enables electroluminescence
      emission up to room temperature.

PMID- 30277077
TI  - Postnovo: Postprocessing Enables Accurate and FDR-Controlled de Novo Peptide
      Sequencing.
AB  - De novo sequencing offers an alternative to database search methods for peptide
      identification from mass spectra. Since it does not rely on a predetermined
      database of expected or potential sequences in the sample, de novo sequencing is
      particularly appropriate for samples lacking a well-defined or comprehensive
      reference database. However, the low accuracy of many de novo sequence
      predictions has prevented the widespread use of the variety of sequencing tools
      currently available. Here, we present a new open-source tool, Postnovo, that
      postprocesses de novo sequence predictions to find high-accuracy results.
      Postnovo uses a predictive model to rescore and rerank candidate sequences in a
      manner akin to database search postprocessing tools such as Percolator. Postnovo
      leverages the output from multiple de novo sequencing tools in its own analyses,
      producing many times the length of amino acid sequence information (including
      both full- and partial-length peptide sequences) at an equivalent false discovery
      rate (FDR) compared to any individual tool. We present a methodology to reliably
      screen the sequence predictions to a desired FDR given the Postnovo sequence
      score. We validate Postnovo with multiple data sets and demonstrate its ability
      to identify proteins that are missed by database search even in samples with
      paired reference databases.

PMID- 30277076
TI  - Chiral Control in Pentacoordinate Systems: The Case of Organosilicates.
AB  - Chirality at the central element of pentacoordinate systems can be controlled
      with two identical bidentate ligands. In such cases the topological Levi
      Desargues graph for all the Berry pseudorotations (BPR, max. 20) reduces to
      interconnected inner and outer "circles" that represent the dynamic enantiomer
      pair. High enough barriers of the BPR crossovers between the two circles is all
      what is needed to ascertain chiral integrity. This is illustrated computationally
      and experimentally for the organosilicates 7 and 10 that carry besides a Me (a),
      Et (b), Ph (c), or F (d) group two bidentate 2-(phenyl)benzo[ b]-thiophene or 2
      (phenyl)naphthyl ligands, respectively. The enantiomers of tetraorganosilane
      precursor 9 could be separated by column chromatography. Their chiral integrity
      persisted on forming the silicates. CD spectra are reported for 10c. Fluoro
      derivative 10d is shown to have its electronegative F substituent in an
      equatorial position, is stable toward hydrolysis, and its enantiomers do not
      racemize at ambient temperatures, while those of 10c racemize slowly.

PMID- 30277075
TI  - Low-Cost Method Generating In Situ Anaerobic Conditions on a 96-Well Plate for
      Microbial Fermentation in Food Research.
AB  - Commercial tools and instruments have been developed for a screening study of
      microbial fermentation, but they are expensive and mostly confined to aerobic
      fermentation only. There is little development on the generation of anaerobic
      conditions directly on a 96-well plate. This report proposed a simple and
      versatile microbial fermentation system known as OVAMO that makes use of Oxyrase,
      vacuum, and mineral oil to generate an in situ anaerobic environment on a 96-well
      plate for at least 48 h. The practicality of OVAMO in anaerobic fermentation
      experiments used for functional food research was validated by a prebiotic
      screening study of different carbohydrates by Bifidobacterium longum subsp.
      infantis. The OVAMO system provides a less expensive but effective way to conduct
      a microbial fermentation screening study that requires anaerobic conditions
      without the need for atmospheric control by external devices.

PMID- 30277078
TI  - NormalyzerDE: Online tool for improved normalization of omics expression data and
      high-sensitivity differential expression analysis.
AB  - Technical biases are introduced in omics datasets during data generation and
      interfere with the ability to study biological mechanisms. Several normalization
      approaches have been proposed to minimize the effects of such biases, but
      fluctuations in the electrospray current during LC-MS gradients causes local and
      sample specific bias not considered by most approaches. Here we introduce a
      software named NormalyzerDE that includes a generic retention time (RT)-segmented
      approach compatible with a wide range of global normalization approaches to
      reduce the effects of time-resolved bias. The software offers straightforward
      access to multiple normalization methods, allows for dataset evaluation and
      normalization quality assessment as well as subsequent or independent
      differential expression analysis using the empirical Bayes Limma approach. When
      evaluated on two spike-in datasets the RT-segmented approaches outperformed
      conventional approaches by detecting more peptides (8 - 36%) without loss of
      precision. Furthermore, differential expression analysis using the Limma approach
      consistently increased recall (2 - 35%) compared to ANOVA. The combination of RT
      normalization and Limma was in one case able to distinguish 108% (2597 vs. 1249)
      more spike-in peptides compared to traditional approaches. NormalyzerDE provides
      widely usable tools for performing, and evaluating the outcome of, normalization
      and makes calculation of subsequent differential expression statistics
      straightforward. The program is available as a web server at
      http://quantitativeproteomics.org/normalyzerde.

PMID- 30277079
TI  - gem-Digold Acetylide Complexes for Catalytic Intermolecular [4 + 2]
      Cycloaddition: Having Two Gold Centers Is Better for Asymmetric Catalysis.
AB  - Gold(I)-catalyzed highly enantioselective intermolecular [4 + 2] cycloaddition is
      shown with ynones and cyclohexadiene. Various bicyclo[2.2.2]octadiene derivatives
      are produced in high yields (up to 99%) with good enantioselectivity (up to 96%
      ee). Key to the success is generation of the gem-digold terminal alkyne as a
      catalytic on-cycle species. As proof of the gem-digold catalysis, a positive
      nonlinear effect is clarified between the ee's of the ligand and the cycloadduct.

PMID- 30277080
TI  - Importance of assessing and adjusting for cross-study heterogeneity in network
      meta-analysis: a case study of psoriasis.
AB  - AIM: The importance of adjusting for cross-study heterogeneity when conducting
      network meta-analyses (NMAs) was demonstrated using a case study of biologic
      therapies for moderate-to-severe plaque psoriasis. METHODS: Bayesian NMAs were
      conducted for Psoriasis Area and Severity Index 90 response. Several covariates
      were considered to account for cross-trial differences: baseline risk (i.e.,
      placebo response), prior biologic use, body weight, psoriasis duration, age, race
      and baseline Psoriasis Area and Severity Index score. Model fit was evaluated.
      RESULTS: The baseline risk-adjusted NMA, which adjusts for multiple observed and
      unobserved effect modifiers, was associated with the best model fit. Lack of
      adjustment for cross-trial differences led to different clinical interpretations
      of findings. CONCLUSION: Failure to adjust for cross-trial differences in NMA can
      have important implications for clinical interpretations when studying the
      comparative efficacy of healthcare interventions.

PMID- 30277081
TI  - Reactive oxygen species are responsible for the cell aggregation and production
      of pro-inflammatory mediators in phorbol ester (PMA)-treated U937 cells on
      gelatin-coated dishes through upregulation of autophagy.
AB  - PURPOSE: Our previous studies indicate that phorbol 12-myristate 13-acetate (PMA)
      treated U937 cells cultured on collagen I -coated dishes express lowered
      production of pro-inflammatory mediators in parallel through reduced Reactive
      oxygen species (ROS) levels. By contrast, PMA-treated U937 cells on gelatin, the
      denatured collagen, show enhanced production of pro-inflammatory mediators,
      mediated by up-regulating autophagy levels. The present study is aimed to
      investigate the effect of ROS levels in PMA-treated U937 cells cultured on
      gelatin-coated surface. MATERIAL AND METHODS: MTT assay, flow cytometric analysis
      of ROS and autophagy, biochemical detection of antioxidant levels, ELISA assay,
      and western blot were used. RESULTS: Gelatin-coating increased ROS levels in PMA
      treated U937 cells. Increased ROS levels are involved in the regulation of cell
      aggregation and the release of pro-inflammatory mediators in gelatin-coated
      culture. These results lead to the query about the crosstalk between the two
      positive regulators, the autophagy and ROS. Autophagy induction is attenuated by
      NAC treatment, but the treatment with autophagy inhibitor, 3-methyladenine, does
      not affect ROS levels, suggesting ROS are upstream of autophagy in the regulation
      axis of differentiated U937 cells on gelatin-coated surface. Further study
      confirmed that upregulation of autophagy was responsible for ROS-induced cell
      aggregation and production of pro-inflammatory mediators. CONCLUSION: The results
      suggest that gelatin-coating promotes the aggregation of PMA-treated U937 cells
      and the production of pro-inflammatory mediators by ROS-autophagy signaling
      pathway.

PMID- 30277082
TI  - Pharmacokinetics of new oral anticoagulants: implications for use in routine
      care.
AB  - INTRODUCTION: Since 2008, new oral anticoagulants (NOACs) have been approved for
      the prevention of venous thromboembolism (VTE) in patients receiving hip or knee
      replacement surgery, prevention of stroke and systemic embolism in patients with
      non-valvular atrial fibrillation (NVAF), treatment of deep vein thrombosis (DVT),
      and pulmonary embolism (PE). Premarketing randomized clinical trials (RCTs) of
      NOACs demonstrated their non-inferiority in terms of efficacy vs. warfarin
      (traditional oral anticoagulant - TOA), with lower risk of serious adverse drug
      reactions, especially cerebral hemorrhages. In clinical practice, pharmacokinetic
      aspects of NOACs have to be carefully taken into account to optimize the benefit
      risk profile of these drugs. Areas covered: An overview of major issues related
      to pharmacokinetics of NOACs, such as drug-drug interactions, over- and
      underdosage in special populations (e.g. elderly, underweight, and chronic kidney
      disease patients), and impact on adherence and persistence to NOACs therapy and
      ultimately clinical outcomes in real-world setting, is provided. Expert opinion:
      NOACs have been proven to be a better option than traditional anticoagulants due
      to better tolerability and ease of use. However, given specific pharmacokinetic
      characteristics, NOAC therapy has to be carefully tailored and monitored in
      relation to patient characteristics with the final goal of maximizing benefits
      and minimizing risks.

PMID- 30277083
TI  - Analysis of the Genotypes in a Chinese Population with Increased Hb A2 and Low
      Hematological Indices.
AB  - Increased Hb A2 is considered the most reliable hematological finding for the
      identification of beta-thalassemia (beta-thal) carriers. The aim of this study
      was to determine the underlying genetic factors associated with a high Hb A2
      level in a Chinese population. Subjects were recruited from couples preparing for
      pregnancy who participated in the thalassemia screening program during a 2-year
      period. DNA analyses were used for diagnosis of beta-thal and other genetic
      factors. A total of 5985 adults who screened positive for beta-thal were
      recruited. Of these, 5933 (99.1%) were detected to have a beta-thal mutation. In
      the remaining 52 (0.9%) individuals without mutations involving the beta-globin
      gene cluster, 16 were found to have Kruppel-like factor 1 (KLF1) gene variants,
      and two had an alpha-globin gene triplication. There were still 34 individuals
      with unknown genetic factors for their raised Hb A2 values. The results of this
      study indicate that genetic factors other than beta-thal can rarely contribute to
      the elevation of Hb A2. These subjects usually have borderline microcytic red
      cell indices and Hb A2 values.

PMID- 30277084
TI  - Infliximab biosimilar CT-P13 therapy is effective in maintaining endoscopic
      remission in ulcerative colitis - results from multicenter observational cohort.
AB  - BACKGROUND: CT-P13, the first biosimilar monoclonal antibody to infliximab (IFX),
      has previously been confirmed to be efficacious in inducing mucosal healing in
      ulcerative colitis (UC) patients. The aim of this study was to evaluate the
      efficacy of CT-P13 therapy in maintaining mucosal healing in UC. METHODS: CT-P13
      trough levels, antibody positivity, serum inflammatory markers as CRP level,
      fecal calprotectin at weeks 14 and 54, concomitant steroid and azathioprine
      therapy at the time of induction therapy and at weeks 14 and 54, previous use of
      anti TNF drug and the need of dose intensification as possible predictive factors
      for mucosal healing at week 54 were evaluated in this prospective study. RESULTS:
      61 patients had already completed the 54-week treatment period. Mucosal healing
      was shown in 65.5 % and 62.1 %, complete mucosal healing was present in 31% and
      38 % at week 14 and 54, respectively. The median values of CRP, leukocytes,
      thrombocytes, and albumin showed significant difference between baseline and week
      54. Serum antibody positivity was proved in 6.5 % and 19.7 % of cases at week 14
      and 54, respectively. CONCLUSION: Our study confirmed the long-term efficacy of
      CT-P13 therapy on mucosal healing in UC.

PMID- 30277086
TI  - Clinical Genotyping by Next Generation Sequencing Reveals a Novel, De Novo beta
      Globin Gene Mutation Causing Hemolytic Anemia in a Chinese Individual.
AB  - Abnormal hemoglobins (Hbs) are one of the most common hemoglobinopathies
      worldwide. Some Hb gene mutations may produce unstable, abnormal Hbs causing
      macrocytic hemolysis. We identified a novel, de novo deletion/frameshift mutation
      at nucleotide position 408 in exon 3 of the beta-globin gene (HBB: c.408delT)
      compound with an Hb F-associated regulatory single nucleotide polymorphism (rSNP)
      (rs368698783) through next generation sequencing (NGS). This beta-globin gene
      variant was identified in a 5-year-old Chinese girl with splenomegaly, jaundice
      and macrocytic, hemolytic anemia. This variant causes a new stop codon to be
      formed in the 3' untranslated region (3'UTR) of the HBB gene at amino acid
      position 158, consequently leading to a beta-sheet disruption of the last alpha
      helix of this abnormal beta-globin chain. We named this variant Hb Urumqi after
      the proband's current city of residence.

PMID- 30277085
TI  - The daily practice of (suspected) coeliac disease management by general
      practitioners: A qualitative approach.
AB  - BACKGROUND: General practitioners (GPs) play a crucial role in diagnosing coeliac
      disease (CD). However, data on GP management of (suspected) CD patients is
      sparse. OBJECTIVES: To provide insights into the daily practice of diagnosis,
      treatment, and follow-up of CD by GPs. METHODS: A qualitative study using topic
      list-based semi-structured in-depth interviews with Dutch GPs with more than five
      years' experience carried out between January and March 2017. GPs were
      purposively sampled. The number of GPs interviewed depended on when data
      saturation was reached. We applied content analysis to the semi-structured
      interviews. RESULTS: Seven GPs were interviewed, five of whom were female.
      Analysis of the interviews resulted in three main themes: 'awareness,'
      'diagnostics' and 'management.' Vague gastrointestinal symptoms and diarrhoea
      were often mentioned as a possible presentation of CD. Antibodies were used in CD
      diagnosis, although some GPs would start a gluten-free diet as a first diagnostic
      tool. Some GPs diagnosed CD only based on positive antibodies without referring
      to secondary care or duodenal biopsy analysis. GPs mentioned no role for primary
      care physicians in the follow-up of CD and noted the important role of dieticians
      in CD management. CONCLUSION: The different views of GPs on how to diagnose and
      monitor CD could be a basis for further research to improve CD detection rate and
      CD care.

PMID- 30277087
TI  - The effects of lycopene on alloxan induced diabetic optic neuropathy.
AB  - AIM: To determine the effects of lycopene treatment in prevention of diabetes
      associated inflammatory response and oxidative stress in an experimental model.
      With this aim we investigated the levels of oxidative stress markers including
      Malondialdehyde (MDA), and total oxidative status (TOS)together with inflammatory
      markers including nuclear factor- kappa B (NFKB) and tumor necrosis factor alpha
      (TNF-alpha) and antioxidants including total glutathione (TGSH), total oxidative
      status (TOS) and total anti-oxidative status (TAS) levels on eye tissue. MATERIAL
      AND METHODS: Totally 18 albino Wistar male rats (250-280 grams) assigned into
      three groups, with six rats in each group as follows: healthy group (HG), control
      group (CG), and lycopene group (LG). The diabetes was induced with alloxan
      administration in rats of CG and LG. Lycopene (4 mg/kg) was administered to the
      rats in LG once a day for 3 months. At the end of this period, the animals were
      sacrificed and their eyes were enucleated for histopathological evaluations. From
      the tissues, MDA, GSH, TOS, TAS, TNF-alpha and NF-kappaB levels were analyzed.
      RESULTS: MDA, TOS, OSI, NFKB and TNF-alpha levels were significantly higher,
      while TGSH and TAS levels were significantly lower in CG compared with HG (p <
      0.001). On the other hand in LG; MDA, TOS, OSI, NFKB and TNF-alpha levels were
      significantly lower, while TGSH and TAS levels were significantly higher compared
      with CG (p < 0.001). Regarding histopathological findings, although there was
      severe damage on optic nerve of rats in CG; there was only a slight damage in
      lycopene administered group. CONCLUSION: For the first time in literature we
      determined that, lycopene was significantly effective in prevention of augmented
      inflammation and oxidative stress on eye tissue associated with diabetes, as well
      as the tissue damage on optic nerve. However, studies investigating the long-term
      clinical effects of lycopene on diabetic individuals are warranted.

PMID- 30277088
TI  - Effectiveness and safety of anti-TNF in psoriatic arthritis patients in Brazil: a
      post-incorporation analysis.
AB  - AIM: Psoriatic arthritis is a chronic disease that can result in disability and
      decreased quality of life. MATERIALS & METHODS: A prospective cohort was
      conducted in Brazil. Disease activity was measured by the Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI) and Clinical Disease Activity Index
      (CDAI), functionality by the Health Assessment Questionnaire Disability Index
      (HAQ-DI) and the quality of life by the EuroQol 5D (EQ-5D). RESULTS: In total,
      122 patients were included. After 6 months, a median reduction of 2.03 in the
      BASDAI, 7.80 in the CDAI, 0.63 in the HAQ-DI and increase of 0.12 in the EQ-5D
      was observed. A good clinical response was observed in 45.5% of the patients by
      BASDAI and 54.5% by CDAI. Higher education and better quality of life were
      identified as predictors of effectiveness. The most common side effects were the
      infections. CONCLUSION: Anti-TNF-alpha drugs were effective and safe. The
      incorporation of them into the Brazilian Public Health System has provided
      therapeutic alternatives to the treatment of psoriatic arthritis.

PMID- 30277089
TI  - A phase 2 study of lenalidomide and dexamethasone in previously untreated
      patients with chronic lymphocytic leukemia (CLL).
AB  - Lenalidomide has anti-tumor activity in CLL but can be complicated by tumor lysis
      syndrome (TLS) and tumor flare (TF). In our previous study using low-dose
      lenalidomide in treatment-naive CLL, TLS was averted but TF remained frequent and
      complete responses (CR) were rare, despite treatment to progression. The addition
      of dexamethasone may mitigate TF and enable lenalidomide dose escalation,
      achieving durable response without long-term use. In this phase 2 trial, 31
      treatment-naive CLL patients received lenalidomide (target 25mg daily) plus
      dexamethasone for a finite 18 cycles. No patients developed TLS and TF was
      infrequent. Overall responses were 74.2% (CR 9.7%) and median progression-free
      survival 27 months. Cereblon-binding proteins IKZF1 and IKZF3 were largely
      downregulated, with associated increased IRF4 levels. We therefore report that
      lenalidomide plus dexamethasone can achieve durable responses in a subset of
      patients without continuing therapy until progression. Upregulation of IRF4 may
      contribute to anti-CLL activity of immunomodulatory agents. This trial was
      registered at www.clinicaltrials.gov as NCT01133743.

PMID- 30277090
TI  - Extracts of different pollen species and their effect on human tear fluid and an
      epithelial cell line.
AB  - PURPOSE: Hazelnut and birch pollen are known to destroy tear film components and
      attack ocular surface cells. We investigated further pollen species from
      different plant families, whether they show similar effects on human tear fluid
      and an epithelial cell line in vitro, to provide a broad basis for further
      research on pollen reactions affecting the tear film and ocular surface.
      MATERIALS AND METHODS: Regional pollen species from different plant families
      (Adoxaceae, Betulaceae, Fagaceae, Juglandaceae, Malvaceae, Oleaceae, Pinaceae,
      Plantaginaceae, Poaceae, Salicaceae, Sapindaceae) were collected. Their
      proteolytic activity was evaluated by Zymography. Human tear fluid and cells of
      an epithelial cell line were incubated with pollen extracts. Tear fluid was
      analyzed by Polyacrylamide gel electrophoresis (PAGE). Cytomorphology was
      assessed microscopically and cell viability by proliferation (MTS), water-soluble
      tetrazolium (WST-1) assay and the impedance-based xCELLigence real-time analysis
      (RTCA). RESULTS: Zymography revealed significant protease activity and PAGE
      showed the degradation of tear proteins by different pollen species. Cells
      incubated with pollen extracts presented dose- and time-dependent
      cytomorphological changes. MTS, WST-1, and RTCA revealed cytostatic as well as
      cytotoxic effects of pollen extracts. CONCLUSIONS: Pollen species from different
      plant families exert proteolytic activity and degrade human tear fluid as well as
      epithelial cells, which may play a crucial role in the pathogenesis of allergic
      and non-allergic reactions affecting the ocular surface.

PMID- 30277091
TI  - Grade II Sylvian fissure meningiomas without dural attachment: case report and
      review of the literature.
AB  - Sylvian fissure meningiomas (SFMs) represent a rare subgroup of nondural-based
      tumors arising from the meningothelial cells within the arachnoid of the Sylvian
      fissure. SFMs are more frequent in young males, usually manifest with seizures
      and display the same radiological features of meningiomas in other locations.
      Although the absence of dural attachment makes these tumors suitable for a
      complete resection, their anatomical relationships with the middle cerebral
      artery branches have impaired its achievement in half of them. To the best of our
      knowledge, only five atypical WHO grade II SFMs have been previously described.
      We provide a literature review of SFMs WHO grades I-II and discuss common
      characteristics and surgical challenges we found in a similar case.

PMID- 30277092
TI  - Most multiple myeloma patients have low testosterone.

PMID- 30277093
TI  - Challenges and importance of measuring neurobehavioural disability in acquired
      brain injury: the 'St Andrew's Swansea - Neurobehavioural Outcomes Scale'
      (SASNOS).

PMID- 30277094
TI  - Long-term treatment with plecanatide was safe and tolerable in patients with
      irritable bowel syndrome with constipation.
AB  - OBJECTIVE: This open-label, multi-center, fixed-dose study (NCT02706483)
      evaluated the long-term safety and tolerability of plecanatide for the treatment
      of adults with irritable bowel syndrome with constipation (IBS-C). METHODS:
      Safety and tolerability of once-daily plecanatide 6 mg for up to 53 weeks was
      assessed in patients with IBS-C who either had been enrolled in one of the phase
      3 studies or were study-naive but met eligibility criteria of the double-blind
      studies. Safety was assessed by treatment-emergent adverse events (AEs). Patient
      reported questionnaires assessed overall IBS symptoms, treatment satisfaction,
      and desire for treatment continuation. No dose adjustments or treatment
      interruptions were permitted during the study. RESULTS: Of the 2272 patients
      enrolled, 1842 (81.1%) completed the study. AEs were experienced by 27.3%, and
      4.3% discontinued due to an AE. Most AEs were mild or moderate (90.3%). The
      incidence of diarrhea, the most commonly reported AE, was low (6.7%), and
      declined in frequency over time. Diarrhea was the most common cause of AE-related
      withdrawals (2.7% of patients). At week 53 or end of treatment, 88.2% of patients
      reported "significant" or "moderate" relief, 72.4% were "very" or "quite"
      satisfied with treatment, and 76.6% were "very" or "quite" likely to continue
      treatment. CONCLUSIONS: Plecanatide 6 mg was safe and well tolerated in patients
      with IBS-C treated for up to 53 weeks, with an overall safety profile similar to
      the 12-week IBS-C studies. Patients reported high rates of relief and
      satisfaction with treatment, and interest in continuing therapy.

PMID- 30277095
TI  - Multichannel electromyography for the assessment of pelvic floor muscle function.

PMID- 30277096
TI  - BACE inhibitors in clinical development for the treatment of Alzheimer's disease.
AB  - INTRODUCTION: The amyloid hypothesis of Alzheimer's disease (AD) affirms that
      brain accumulation of amyloid-beta (Abeta) oligomers and soluble aggregates
      represent the major pathological event of the disease. Several anti-Abeta small
      organic molecules, monoclonal antibodies and antigens were developed to interfere
      with Abeta production and clearance, including beta-site amyloid precursor
      protein cleaving enzyme (BACE) inhibitors, blocking the first enzymatic step of
      Abeta formation. All these approaches, including BACE inhibitors, have failed in
      large randomized clinical trials (RCTs) in mild-to-moderate AD, but further
      studies are now being carried out in patients at early AD stages and in
      asymptomatic subjects at risk of developing AD. Areas covered: The paper provides
      a comprehensive review of BACE inhibitors for AD treatment, focusing on the most
      advanced compounds in Phase III RCTs. Expert commentary: BACE inhibitors
      inhibited robustly, and dose-dependently, Abeta formation in cerebrospinal fluid
      of AD patients, but without cognitive, clinical, or functional benefit in large
      RCTs. BACE inhibition may be not sufficient to decrease brain Abeta plaques and
      aggregates. Indeed, several BACE inhibitors were found to be poorly tolerated and
      some of them failed also in patients with prodromal AD. This may indicate that
      blocking the formation of nascent Abeta is not useful in AD.

PMID- 30277097
TI  - A Novel beta-Globin Gene Mutation: Hb Shenzhen [beta90(F6)Glu->Ala, HBB:
      c.272A>C].
AB  - We report a novel beta-globin chain variant, Hb Shenzhen [beta90(F6)Glu->Ala,
      HBB: c.272A>C], in a 52-year-old Chinese individual. The hemoglobin (Hb) variant
      takes the position of the Hb D zone using capillary electrophoresis. Sanger
      sequencing revealed a novel base mutation on the beta-globin gene, HBB: c.272A>C,
      that resulted in a transition of glutamic acid to alanine at exon 2 of the beta
      globin gene. We named this novel variant Hb Shenzhen for the geographic origin of
      this proband.

PMID- 30277098
TI  - Characterization of two new high-grade B-cell lymphoma cell lines with MYC and
      BCL2 rearrangements that are suitable for in vitro drug sensitivity studies.
AB  - High-grade B-cell lymphomas with MYC and BCL2 or BCL6 rearrangements are highly
      aggressive B-cell lymphomas called double-hit lymphomas (HGBL-DH). They are
      particularly refractory to standard treatments and carry a poor prognosis.
      Fragments of resected tumoral lymph nodes from two HGBL-DH patients were put in
      culture. Continuously proliferating cells were characterized and compared with
      the original tumors. In both cases, the proliferating cells and the tumor
      displayed MYC and BCL2 rearrangements. Both cell lines (called LB5848-LYMP and
      LB5871-LYMP) presented a high proliferation rate and were maintained in culture
      for more than one year. Upon injection in immunodeficient mice, LB5848-LYMP gave
      rise to lymphoid tumors. In vitro treatment of these cell lines with a BCL2
      inhibitory drug (ABT-199) selectively stopped their proliferation. These new cell
      lines represent valuable tools for studying HGBL-DH and for the in vitro testing
      of candidate therapies targeting HGBL-DH. LB5848-LYMP is also suitable for
      similar experiments in vivo.

PMID- 30277099
TI  - Adverse events, resource use, and economic burden associated with mantle cell
      lymphoma: a real-world assessment of privately insured patients in the United
      States.
AB  - In view of recent therapeutic advances in mantle cell lymphoma (MCL), the aim of
      this retrospective cohort analysis was to assess treatment patterns, adverse
      events (AEs), resource utilization, and health care costs in patients with MCL in
      a US-based commercial claims database. A total of 783 patients with MCL (median
      age = 65 years) were selected. Among patients receiving systemic therapy (n =
      457), the most common treatment regimens were bendamustine/rituximab (BR)
      (41.1%), rituximab/cyclophosphamide/doxorubicin/vincristine (RCHOP) (26.7%),
      rituximab monotherapy (20.4%), and ibrutinib monotherapy (14.2%). Mean monthly
      costs during treatments with BR, RCHOP, rituximab, and ibrutinib were $12,958,
      $24,719, $13,153, and $21,690, respectively. Mean monthly cost during follow-up
      was $13,650 among patients with >=6 AEs versus $5131 among those without AEs. The
      costs of MCL varied considerably by treatment regimen and care setting. The
      overall economic burden of managing patients with MCL can be substantially
      affected by costs associated with managing AEs occurring during treatment.

PMID- 30277100
TI  - Augmented myeloablative conditioning with thiotepa in acute myeloid leukemia -
      improved outcomes with similar toxicity.
AB  - Myeloablative doses of busulfan (Bu) with fludarabine (Flu) have reduced
      toxicity, however, limited by an increased relapse rate. We aimed to improve
      outcome of Flu-Bu regimen by augmentation with thiotepa (TT) (10 mg/kg). Eighty
      nine patients with AML, 44 patients conditioned with Flu-Bu (group 1), and 45
      patients augmented with TT (Flu-Bu-TT, group 2), were retrospectively analyzed.
      Primary objectives were toxicity and outcomes. Major toxicities were comparable:
      mucositis (p = 1.0), sepsis (p = .7), severe venocclusive disease of liver (VOD)
      (p = 1.0), and non-relapse mortality (NRM) (22 vs. 22%, p = .7). Five-year
      disease-free survival was significantly better in group 2 compared to group 1 (62
      vs. 38%, p = .02). Five-year overall survival (OS) showed trend toward benefit in
      group 2 (62 vs. 42%, p = .06). Lower relapse rate in group 2 (14 vs. 46%, p =
      .005) contributed to better outcomes. Augmented regimen has better disease-free
      survival (DFS) (mainly due to reduced relapse rate) and similar toxicities as
      compared to Flu-Bu. Key points  Assessing the addition of TT to myeloablative
      conditioning (Flu, Bu) in patients undergoing allogeneic stem cell transplant for
      acute myeloid leukemia with regard to relapse rate, disease-free survival and
      toxicity.  Addition of thiotepa improves disease-free survival and shows trend
      toward benefit in overall survival, by reducing relapses without additional
      toxicity.

PMID- 30277101
TI  - Characterizing the kinetics of lymphocytosis in patients with chronic lymphocytic
      leukemia treated with single-agent ibrutinib.
AB  - Increased absolute lymphocyte count (ALC) is a key feature of chronic lymphocytic
      leukemia (CLL) but is also observed during treatment with B-cell receptor pathway
      inhibitors including ibrutinib, a first-in-class inhibitor of Bruton's tyrosine
      kinase. In patients with CLL treated with single-agent ibrutinib in two
      multicenter, open-label, randomized, phase 3 studies (RESONATE-2, NCT01722487;
      RESONATE, NCT01578707), lymphocytosis was observed in 77 of 136 (57%) patients
      treated in first-line and 133 of 195 (69%) relapsed/refractory patients. On
      treatment, lymphocytosis resolved in 95% of patients in the first-line and 94% in
      the relapsed/refractory setting. The median duration of lymphocytosis was 12 and
      14 weeks in the first-line and relapsed/refractory settings, respectively.
      Lymphocytosis is a common and predictable pharmacodynamic effect of ibrutinib
      treatment, and in the absence of other signs of progression, does not represent
      disease progression. Lymphocytosis resolves in the majority of patients and does
      not require interruption or discontinuation of ibrutinib therapy.

PMID- 30277103
TI  - The JAK inhibitor antcin H exhibits direct anticancer activity while enhancing
      chemotherapy against LMP1-expressed lymphoma.
AB  - Epstein-Barr virus (EBV) infection is associated with B cell lymphomas in humans.
      The latent membrane protein 1 (LMP-1) of EBV constitutively activates the
      JAK/STAT signaling pathway and contributes to the proliferation of EBV-infected
      primary human B lymphocytes. Thus, targeting LMP1-induced JAK/STAT signaling may
      prove effective in treating B-cell lymphomas. The extract of the fruiting body of
      Antrodia cinnamomea, has been reported to have cytotoxicity on blood cancer
      cells. Here, we report that the bioactivity of antcin H, an analog of the JAK2
      inhibitor zhankuic acid A (ZAA), inhibits LMP1-induced JAK/STAT related signaling
      and induces lymphoma cell line apoptosis. Moreover, antcin H enhances low-dose
      methotrexate (MTX) cytotoxicity against lymphoma cells. Treatment of antcin H
      with low-dose MTX significantly suppressed tumor growth and prolonged the
      survival of tumor-bearing mice. Our findings indicate antcin H as a potential
      therapeutic agent for the treatment of EBV-infected cancer cells.

PMID- 30277102
TI  - Obinutuzumab plus CHOP is effective and has a tolerable safety profile in
      previously untreated, advanced diffuse large B-cell lymphoma: the phase II GATHER
      study.
AB  - This study investigated the safety and efficacy of obinutuzumab plus
      cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP) in patients
      with advanced diffuse large B-cell lymphoma (DLBCL) and explored the impact of
      cell-of-origin (COO) on patient outcomes. Patients (N = 100) received
      obinutuzumab (1000 mg on the days 1, 8, and 15 of cycle 1, and day 1 of cycles 2
      8) plus CHOP (cycles 1-6). For patients without grade >=3 infusion-related
      reactions (IRRs) to standard-rate obinutuzumab infusion, a shorter duration of
      infusion (SDI) was evaluated. Overall and complete response rates, as determined
      according to the Cheson et al. criteria by investigators/independent radiological
      facility, were 82.0/75.0% and 55.0/58.0%, respectively. SDI of 120 minutes and 90
      minutes were well tolerated with no grade >=3 IRRs. Among all patients, IRRs
      typically occurred during cycle 1, day 1. G-CHOP is active and has an acceptable
      safety profile in the first-line treatment of patients with advanced DLBCL.
      Clinical Trials: NCT01414855DLBCL.

PMID- 30277104
TI  - Is there an order of loss of sounds in speakers with Parkinson's disease?
AB  - Influential reports on speech changes in people with Parkinson's disease (PD;
      Logemann et al., 1978, 1981) reported a posterior to anterior pattern of loss of
      speech sound accuracy. These claims have never been examined. In a partial
      replication of Logemann et al.'s work, we examined whether posterior lingual
      sounds are most affected in people with Parkinson's disease, followed by anterior
      lingual sounds and then labial sounds. Ninety-nine people with PD (age: mean
      70.7, SD 8.46; time since diagnosis: mean 6.97, SD 6.2) with mild to severe
      overall motor symptoms (Hoehn and Yahr stages 1-5, median 2.5) completed a
      diagnostic intelligibility test. This was scored by 60 listeners unfamiliar with
      PD and dysarthric speech. We calculated the proportion of posterior versus
      anterior lingual versus labial sounds misrecognized by the listeners. We compared
      profiles of misperceived sounds within and across Hoehn and Yahr stages of
      severity and in relation to Unified Parkinson's Disease Rating Scale (UPDRS) and
      speech intelligibility scores. Speech accuracy declined significantly in relation
      to overall motor impairment for labial and anterior lingual sounds but not for
      velar sounds. Speech sound accuracy was strongly associated with intelligibility
      outcomes (p = < 0.01). Contrary to previous assertions, there was no evidence
      supporting the existence of a posterior to anterior order of 'loss' of oral
      speech sounds in people with PD, nor an interaction of anterior-posterior speech
      profile changes with Hoehn and Yahr stage. Findings support the notion that a
      common underlying impairment of movement downscaling affects all sounds similarly
      and simultaneously in PD from the start.

PMID- 30277106
TI  - Pomalidomide - Author Reply.

PMID- 30277105
TI  - The size and depth of lesions measured by endoscopic ultrasonography are novel
      prognostic factors of primary gastric diffuse large B-cell lymphoma.
AB  - Diffuse large B cell lymphoma is one of the predominant histological subtypes of
      primary gastric lymphomas. Factors that contribute to precise stratification and
      guide the treatment of this disease are still not well understood. We analyzed 73
      primary gastric diffuse large B cell lymphoma patients retrospectively, and found
      that patients characterized by late stage, multiple localization, B symptoms,
      lower serum albumin level and elevated LDH level had a shorter overall survival
      through Univariate Cox regression analysis. Multivariate Cox regression analysis
      demonstrated that ALB <= 35g/L, staging >= IIE and multiple sites localization
      were independent adverse prognostic factors. Significantly, in 35 patients who
      received endoscopy at diagnosis, Kaplan-Meier analyses indicated that patients
      with large (>=3 cm) and deep lesions (>=11 mm) had an inferior OS (p = .01 and
      .039). These findings implicated that tumor size and depth are two indicators of
      prognosis under ultrasonography. Further randomized studies with large number of
      cases are needed.

PMID- 30277107
TI  - FLAG salvage therapy combined with idarubicin in relapsed/refractory acute
      myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is characterized by a high failure rate to achieve
      complete remission as well as high relapse rates that cause an emergent need for
      efficient and tolerable salvage therapies. The combination of FLAG with
      idarubicin (FLAG-Ida) is a widely used protocol. However, its efficacy has been
      analyzed in only a limited number of studies with majorly small patient cohorts.
      Here, we analyzed 132 patients with largely primary refractory or first-time
      relapsed AML treated according to the FLAG-Ida protocol. The overall complete
      remission rate (CR + CRi) was 56% with a median overall survival of 15 months
      (95% CI, 5.7-25.1). The median disease-free survival for CR/CRi-patients was not
      reached. The mortality rate on day 30 was 9% and increased on day 60 to 16%. Our
      results show in relapsed/refractory AML patients a high efficacy and
      compatibility for the FLAG-Ida regimen.

PMID- 30277109
TI  - Monozygotic twins with non-Down syndrome associated MLL-rearranged hematologic
      malignancy and megakaryoblastic differentiation.

PMID- 30277108
TI  - Granulocyte colony-stimulating factor and respiratory status of critically ill
      neutropenic patients with hematologic malignancies.
AB  - In patients with hematologic malignancies, respiratory status may deteriorate
      during neutropenia recovery. This multicenter, observational study aims to
      evaluate granulocyte colony-stimulating factor (G-CSF) impact on respiratory
      status in critically ill neutropenic patients. Among 1011 critically ill patients
      with hematologic malignancies, 288 were neutropenic and included in this study.
      201 (70%) did not receive G-CSF at day 1 or 2. After propensity score matching
      for the probability of receiving G-CSF at day 1 or 2, there was no association
      between G-CSF and respiratory deterioration at day 14 (OR =1.19; 95%CI (0.57
      2.51); p = .64). Additional sensitivity analysis in patients admitted for acute
      respiratory failure showed similar results (OR =1.34; 95%CI (0.5-3.59); p = .57).
      Among patients who recovered from neutropenia, 75% experienced respiratory
      deterioration during neutropenia recovery. This study confirms that neutropenia
      recovery is a situation at risk of respiratory deterioration. However, whether G
      CSF is an aggravating factor cannot be supported by our results.

PMID- 30277112
TI  - A comparison of patients with acute myeloid leukemia and high-risk
      myelodysplastic syndrome treated on versus off study.
AB  - Patients with newly diagnosed (ND) and relapsed/refractory (RR) acute myeloid
      leukemia (AML) and high-risk myelodysplastic syndrome (MDS, >=10% blasts) often
      receive intensive chemotherapy at diagnosis and relapse. We retrospectively
      identified 365 patients and categorized the reasons for receiving treatment off
      study (medical, logistical, or unclear). The pretreatment characteristics of the
      on and off study groups were similar. Rates of the complete remission (CR)
      without measurable residual disease were significantly higher for ND patients
      treated on versus off study (61% versus 35%), but CR rates and survival were low
      for all RR patients regardless of study assignment. The subset of ND patients
      treated off study for medical reasons had significantly decreased overall
      survival and relapse-free survival. Standard, stringent study eligibility
      criteria may delineate a population of ND, but not RR, patients with improved
      outcomes with intensive induction chemotherapy.

PMID- 30277110
TI  - Efficacy of salvage chemotherapy in diffuse large B cell lymphoma with primary
      treatment failure according to putative cell of origin.
AB  - We evaluated outcome of 235 primary treatment failure (PTF) diffuse large B-cell
      lymphoma (DLBCL) patients based on salvage chemotherapy regimen and putative cell
      of-origin (COO). Patients were divided into two groups; group A (n = 38) received
      high-dose cytarabine containing regimen, either DHAP or ESHAP. Patients in group
      B (n = 197) received ifosfamide, carboplatin, and etoposide (ICE) +/- rituximab.
      No difference in overall response rates (CR + PR) was observed based on salvage
      chemotherapy regimen and COO. After adjustment for the presence of ultra high
      risk features, overall survival of germinal center B-cell like (GCB) DLBCL
      patients in group A was not significantly different from survival in group B (HR
      0.86, 95% CI 0.46-1.60, p = .64). Similarly, within non-GCB DLBCL cohort,
      survival in group A was comparable to group B (HR 0.53, 95% CI 0.20-1.44, p =
      .21). We did not find an outcome difference between two commonly used salvage
      chemotherapy regimens in patients with PTF DLBCL based on COO.

PMID- 30277111
TI  - Elderly acute lymphoblastic leukemia: a Mayo Clinic study of 124 patients.
AB  - Poor outcomes in elderly acute lymphoblastic leukemia (ALL) are well recognized,
      but the contributors are ill-defined. We characterized 124 patients >=60 years
      old at our institution. The majority (n = 102, 82%) were treated with intensive
      chemotherapy. Of these, 8/102 (8%) died within the first 100 days; 92/102 (90%)
      achieved complete remission (CR/CRi). Only 31/124 (25%) patients underwent
      allogeneic hematopoietic stem cell transplantation. The median overall survival
      (OS) for the entire cohort was 19.8 months. In a multivariate analysis, ECOG
      performance status >=2, high white blood cell count, and high lactate
      dehydrogenase (at time of diagnosis) negatively influenced OS (p<.01). In a
      subgroup analysis of the intensive treatment group, BCR-ABL1+ patients had
      markedly better OS (hazard ratio 0.3, 95% CI 0.1-0.7; p<.01). In summary, despite
      few early deaths and a high CR/CRi rate, elderly ALL continues to have a poor
      prognosis, underscoring the need for more effective therapies.

PMID- 30277113
TI  - Changes in the inflammatory and oxidative stress markers during a single
      hemodialysis session in patients with chronic kidney disease.
AB  - BACKGROUND: Cardiovascular disease (CVD) is a common cause of morbidity and
      mortality in end-stage renal disease (ESRD) patients on hemodialysis (HD) among
      whom it is 5-20 times higher than in the general population. Some of the
      nontraditional risk factors such as oxidative stress and inflammation are related
      to the progress of CVD in HD patients. Several, but not all studies, reported
      that inflammatory and oxidative stress markers are increased during a single
      session of HD, mimicking changes that occur during acute immune activation. This
      study was taken up to evaluate the changes in the inflammatory and oxidative
      stress markers during a single HD session in patients with chronic kidney
      disease. METHODS: Twenty-five ESRD patients on maintenance HD and 25 controls
      were included in the study. Blood samples were obtained from the patients before
      starting of hemodialysis (pre-HD) and after completion of hemodialysis (post-HD).
      The changes in serum Pentraxin-3, hs-CRP, malondialdehyde (MDA) and ferric
      reducing ability of plasma (FRAP) levels were measured in pre- and post-HD ESRD
      patients and compared with healthy control group. RESULTS: This study found
      increased levels of Pentraxin-3, hs-CRP, MDA, and decreased level of FRAP in HD
      patients compared to controls. CONCLUSIONS: Hemodialysis procedure contributes to
      inflammation and oxidative stress.

PMID- 30277115
TI  - Panoramic view of common fusion genes in a large cohort of Chinese de novo acute
      myeloid leukemia patients.
AB  - Fusion genes are major molecular biological abnormalities in hematological
      malignancies. This study aimed to depict the common recurrent gene-fusion
      landscape in acute myeloid leukemia (AML). 3135 de novo AML cases were enrolled
      and 36 recurrent fusion genes were assessed using multiplex-nested RT-PCR. Twenty
      three distinct fusion genes were detected in 1292 (41.21%) cases. The incidence
      of fusion genes was higher in pediatric AML than in adult cases. The pediatric
      patients had higher incidences of RUNX1-RUNX1T1, KMT2A-MLLT3, KMT2A-MLLT10, KMT2A
      MLLT11, KMT2A-MLLT6, and FUS-ERG, whereas KMT2A-PTD was more common in adult
      patients. The occurrence of molecular abnormalities involving the KMT2A gene and
      CBFB-MYH11 was lower in Chinese pediatric AML compared to Western reports. The
      incidence of RUNX1-RUNX1T1 was higher in both pediatric and adult patients in our
      study than in Western countries. This study provides a genetic landscape of
      common fusion genes in Chinese AML and confirms different incidences between age
      groups and races.

PMID- 30277114
TI  - Methylation of imprinted IGF2 regions is associated with total, visceral, and
      hepatic adiposity in postmenopausal women.
AB  - Excess body fat, especially intra-abdominal fat, is a leading risk factor for
      metabolic diseases. Differentially methylated regions (DMRs) of two imprinted
      genes, insulin-like growth factor 2 (IGF2) and H19, have been associated with
      obesity due to their important roles in regulating body composition, but have not
      been examined in relation to intra-abdominal fat depots. Total body fat from
      whole-body dual energy X-ray absorptiometry and visceral and liver fat contents
      from abdominal magnetic resonance imaging in 48 healthy women aged 60-65 years
      (of White or Japanese ancestry) were each regressed on circulating leukocyte DNA
      methylation levels of IGF2 (at DMR0, DMR2a, and DMR2b) and H19 (at CTCF3) as
      assessed by pyrosequencing, while adjusting for age and race/ethnicity. Total fat
      mass was inversely associated with methylation levels of IGF2 DMR2b (P = 0.016).
      Total fat-adjusted visceral fat area (P = 0.062) and percent visceral fat
      measured at L4-L5 (P = 0.045) were associated with higher methylation levels of
      IGF2 DMR2b. Both total fat-adjusted percent liver fat (P = 0.039) and the
      presence of fatty liver (P = 0.015) were positively associated with IGF2 DMR2a
      methylation. Methylation levels of H19 CTCF3 were not associated with overall or
      intra/abdominal adiposity. The findings indicate that methylation levels of IGF2
      DMR regions in leukocytes are associated with total body fat and with fat
      distribution in the viscera and liver independently of total adiposity.

PMID- 30277116
TI  - Non-NAD-like PARP1 inhibitor enhanced synthetic lethal effect of NAD-like PARP
      inhibitors against BRCA1-deficient leukemia.

PMID- 30277117
TI  - Cytotoxic effect caspase activation dependent of a genetically engineered fusion
      protein with a CD154 peptide mimetic (OmpC-CD154p) on B-NHL cell lines is
      mediated by the inhibition of bcl-6 and YY1 through MAPK p38 activation.
AB  - The interaction between CD40, and its ligand, CD154, is essential for the
      development of humoral and cellular immune responses. The selective inhibition or
      activation of this pathway forms the basis for the development of new
      therapeutics against immunologically based diseases and malignancies. We are
      developing a gene fusion of Salmonella typhi OmpC protein expressing the CD154
      Tyr140-Ser-149 amino acid strand. This OmpC-CD154 binds CD40 and activates B
      cells. In this study, we demonstrate that OmpC-CD154p treatment inhibits cell
      growth, proliferation and induced apoptosis in the B-NHL cell lines Raji and
      Ramos. The Bcl-2 family proteins were regulated and the Bcl-6 and YY1
      oncoproteins were inhibited. p38 MAPK activation is an important mechanism
      underlying the effect on proliferation and apoptosis mediated by this fusion
      protein. This study establishes a basis for the possible use of fusion protein
      OmpC-CD154 as an alternative treatment for B-NHL.

PMID- 30277118
TI  - Xylella fastidiosa subsp. pauca and fastidiosa colonize Arabidopsis systemically
      and induce anthocyanin accumulation in infected leaves.
AB  - The bacterium Xylella fastidiosa is multi-host pathogen that affects perennial
      crops such as grapevine, sweet orange, and olive tree worldwide. It is inherently
      difficult to study these pathosystems owing to the long-term growth habit of the
      host plant. Thus, the availability of model plants becomes essential to
      accelerate discoveries with economic impact. In this study, we uncovered evidence
      that the model plant Arabidopsis thaliana can be colonized by two different
      Xylella fastidiosa subspecies, pauca and fastidiosa. We observed that these
      bacteria are able to move away from the inoculation point as high bacterial
      populations were found in distant tissues. In addition, confocal laser scanning
      microscopy analysis of bacterial movement inside the petiole revealed the ability
      of the bacterium to move against the net xylem flow during the time course of
      colonization forming biofilm. These findings provide evidence for the capacity of
      X. fastidiosa to colonize Arabidopsis. Furthermore, leaves inoculated with X.
      fastidiosa showed a significant accumulation of anthocyanin. We propose that the
      X. fastidiosa subsp. pauca or fastidiosa colonization pattern and anthocyanin
      accumulation in the Arabidopsis ecotype Col-0 can be used as marker phenotypes to
      facilitate further studies aimed at improving genetic components involved in X.
      fastidiosa-host interaction.

PMID- 30277119
TI  - Genome-wide association studies identified resistance loci to orange rust and
      yellow leaf virus diseases in sugarcane (Saccharum spp.).
AB  - Sugarcane (Saccharum spp.) supplies globally ~ 80% of table sugar and 60% of bio
      ethanol. Sugarcane orange rust and sugarcane yellow leaf virus (SCYLV) are major
      sugarcane diseases, causing up to 50% and 40% yield losses respectively.
      Sugarcane cultivars resistant to these diseases are needed to sustain sugarcane
      production in several regions. Dissecting DNA sequence variants controlling
      disease resistance provides a valuable tool for fulfilling a breeding strategy to
      develop resistant cultivars. In this study, we evaluated disease reactions to
      orange rust and SCYLV of a sugarcane diversity panel in repeated trials. We
      conducted a genome-wide association study between high-density markers and
      disease-resistance reactions. We identified 91 putative DNA markers and 82
      candidate genes significantly associated with resistance to one of the two
      diseases. These provide an important genetic resource for finding genes and
      molecular markers for disease resistance. Our results emphasized the importance
      of utilizing a wide germplasm collection for breeding resistant sugarcane
      cultivars.

PMID- 30277120
TI  - The incidence of bleomycin induced lung toxicity is increased in Hodgkin lymphoma
      patients over 45 years exposed to granulocyte-colony stimulating growth factor ?.
AB  - In Hodgkin lymphoma (HL) bleomycin can induce pulmonary toxicity (BPT). BPT
      consists of respiratory tract symptoms during bleomycin-exposure and radiologic
      pulmonary lesions without concomitant infection. Older age, bleomycin dose,
      smoking history and the use of granulocyte-colony stimulating factor (G-CSF) have
      been suggested as possible risk factors for BPT. It is still debated whether BPT
      affects overall (OS) and progression-free survival (PFS). We investigated the
      incidence of BPT along with possible risk factors in 412 HL patients treated in
      1990-2014. BPT occurred in 34 patients (8%) and was significantly associated with
      disseminated disease and B-symptoms. It was more frequent in elderly patients (p
      = .05) but not significantly correlated with a history of smoking. BPT occurred
      more often in patients receiving G-CSF (p = .03), particularly the poly
      ethylenglycol-bound molecule. All significant risk correlations were limited to
      the age group >45 years. In the present cohort, BPT did not influence OS or PFS
      regardless of age.

PMID- 30277121
TI  - Twelve tips for responding to microaggressions and overt discrimination: When the
      patient offends the learner.
AB  - Microaggressions and expressions of overt discrimination negatively affect the
      experience of medical trainees at all levels. Mistreatment of trainees, including
      abusive and discriminatory behavior by patients and families, occurs commonly and
      is receiving increased attention in both the medical literature and popular
      press. Heightened awareness of the problem has sparked a call to engage in
      substantive conversations about bias in health professions education. The
      emphasis on direct observation in medical education makes the bedside a common
      setting for educators to witness these behaviors firsthand. Many educators are
      committed to developing a positive climate for learners but lack the training and
      skills to facilitate discussions about discrimination. As a result, these
      difficult but important conversations may not occur. The authors present a three
      phase approach to responding to microaggressions and discrimination toward
      trainees from patients, and offer a communication toolkit that frontline medical
      educators can use in their daily practice.

PMID- 30277123
TI  - Two cases of reversible Fanconi syndrome induced by lenalidomide.

PMID- 30277124
TI  - The power of the partner: defying expectations in a case of a myeloproliferative
      neoplasm with FGFR1 rearrangement.

PMID- 30277122
TI  - Research articleHemolysis in human erythrocytes by Clostridium perfringens
      epsilon toxin requires activation of P2 receptors.
AB  - Epsilon-toxin (ETX) is produced by types B and D strains of Clostridium
      perfringens, which cause fatal enterotoxaemia in sheep, goats and cattle.
      Previous studies showed that only a restricted number of cell lines are sensitive
      to ETX and ETX-induced hemolysis has not previously been reported. In this study,
      the hemolytic ability of ETX was examined using erythrocytes from 10 species
      including murine, rabbit, sheep, monkey and human. We found that ETX caused
      hemolysis in human erythrocytes (HC50 = 0.2 MUM) but not erythrocytes from the
      other test species. Moreover, the mechanism of ETX-induced hemolysis was further
      explored. Recent studies showed that some bacterial toxins induce hemolysis
      through purinergic receptor (P2) activation. Hence, the function of purinergic
      receptors in ETX-induced hemolysis was tested, and we found that the non
      selective P2 receptor antagonists PPADS inhibited ETX-induced lysis of human
      erythrocytes in a concentration-dependent manner, indicating that ETX-induced
      hemolysis requires activation of purinergic receptors. P2 receptors comprise
      seven P2X (P2X1-7) and eight P2Y (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11-P2Y14)
      receptor subtypes. The pattern of responsiveness to more selective P2-antagonists
      implies that both P2Y13 and P2X7 receptors are involved in ETX-induced hemolysis
      in human species. Furthermore, we demonstrated that extracellular ATP is likely
      not involved in ETX-induced hemolysis and the activation of P2 receptors. These
      findings clarified the mechanism of ETX-induced hemolysis and provided new
      insight into the activities and ETX mode of action.

PMID- 30277125
TI  - A simple score based on geriatric assessment predicts survival in elderly newly
      diagnosed chronic lymphocytic leukemia patients.

PMID- 30277126
TI  - Association between AXL promoter methylation and lung function growth during
      adolescence.
AB  - AXL is one of the TAM (TYRO3, AXL and MERTK) receptor tyrosine kinases and may be
      involved in airway inflammation. Little is known about how epigenetic changes in
      AXL may affect lung development during adolescence. We investigated the
      association between AXL DNA methylation at birth and lung function growth from 10
      to 18 years of age in 923 subjects from the Children's Health Study (CHS). DNA
      methylation from newborn bloodspots was measured at multiple CpG loci across the
      regulatory regions of AXL using Pyrosequencing. Linear spline mixed-effects
      models were fitted to assess the association between DNA methylation and 8-year
      lung function growth. Findings were evaluated for replication in a separate
      population of 237 CHS subjects using methylation data from the Illumina
      HumanMethylation450 (HM450) array when possible. A 5% higher average methylation
      level of the AXL promoter region at birth was associated with a 48.4 ml decrease
      in mean FEV1 growth from 10 to 18 years of age in the primary study population
      (95% CI: -100.2, 3.4), and a 53.9 ml decrease in mean FEV1 growth from 11 to 15
      years of age in the replication population (95% CI: -104.3, -3.5). One CpG locus
      in the promoter region, cg10564498, was significantly associated with decreased
      growth in FEV1, FVC and MMEF from 10 to 18 years of age and the negative
      associations were observed in a similar age range in the replication population.
      These findings suggest a potential association between AXL promoter methylation
      at birth and lower lung function growth during adolescence.

PMID- 30277127
TI  - Health risk due to chronic heavy metal consumption via cow's milk produced in
      Puebla, Mexico, in irrigated wastewater areas.
AB  - The aim of this study was to determine the heavy metals content of milk from cows
      fed with forage irrigated with waste water from industrial sources and the health
      risk to children. Milk samples were taken from milk collection tanks of eight
      localities in the state of Puebla. On average, the heavy metals in the milk had
      the following order Zn> As> Pb > Cr> Cu > Ni. Pb (0.03 mg kg-1) exceeded the
      Codex limits. For As the hazard index was 8.0 +/- 0.4, which is far above 1. On
      the other hand, the individual risk of cancer showed a descending order Cr> As >
      Pb, while the risk of total cancer (0.004 +/- 0.002) indicated that the combined
      effect of heavy metals created a serious risk for girls and children.

PMID- 30277128
TI  - Mesenchymal stem cells in myeloproliferative disorders - focus on primary
      myelofibrosis.
AB  - Primary myelofibrosis (PMF) is the most aggressive Philadelphia-negative (Ph-)
      myeloproliferative neoplasm (MPN), characterized by bone marrow (BM)
      insufficiency, myelofibrosis (MF), osteosclerosis, neoangiogenesis, and
      extramedullary hematopoiesis (EMH) in spleen and liver. Presently, there is no
      curative treatment for this disease and therapy consists primarily of symptom
      relief and, in selected cases, allogeneic hematopoietic stem cell transplant
      (alloHSCT). PMF's major defining characteristics, as well as several recently
      described aspects of its cellular and molecular pathophysiology all support a
      critical role for dysregulated cell-cell/cell-extracellular matrix interactions
      and cytokine/chemokine signaling within the BM niche in the natural history of
      this disease. This review will highlight current data concerning the involvement
      of the BM niche, particularly of mesenchymal stem cells (MSC), in PMF, and will
      then discuss the rationale for a stroma-directed treatment, and the advantages
      such an approach would offer over the current treatments focused on targeting the
      malignant clone.

PMID- 30277130
TI  - Risky intimacies across the lifespan.

PMID- 30277129
TI  - ASXL1 mutations in idiopathic cytopenias: determined significance?

PMID- 30277131
TI  - IL-10 is overexpressed in human cutaneous T-cell lymphoma and is required for
      maximal tumor growth in a mouse model.
AB  - A crucial question pertains to a role of IL-10 as a tumorigenic factor, or just a
      marker of advanced disease in cutaneous T-cell lymphoma (CTCL). Herein, we
      measured significantly elevated IL-10 mRNA in a cohort of skin samples of
      patients with CTCL. Increased IL-10 was also detected in the tumor
      microenvironment of an established inflammation-dependent murine model of using
      MBL2 T lymphoma cells. Conditioned media from MBL2 cells was able to stimulate IL
      10 production in bone marrow-derived macrophages in an IL-4-dependent manner.
      Implanted MBL2 T-cell lymphomas in IL-10KO mice were 50% smaller, accompanied by
      decreased numbers of infiltrating macrophages and reduced efficiency of M2
      polarization compared with wild-type mice. With anti-IL-10R mAb treatment, both
      wild-type tumor-bearing mice and IL-10KO mice exhibited a further growth
      inhibition. Our data indicate that targeting IL-10 signaling with neutralizing
      antibodies to IL-10 or its receptor may have a great potential for advanced CTCL
      therapy.

PMID- 30277132
TI  - Thiol redox-sensitive cationic polymers for dual delivery of drug and gene.
AB  - Recently greater emphasis has been given to combination therapy for generating
      synergistic effects of treating cancer. Recent studies on thiol-sensitive
      nanocarriers for the delivery of drug or gene have shown promising results. In
      this review, we will examine the rationale and advantage in using nanocarriers
      for the combined delivery of different anticancer drugs and biologics. Here, we
      also discuss the role of nanocarriers, particularly redox-sensitive polymers in
      evading or inhibiting the efflux pump in cancer and how they modulate the
      sensitivity of cancer cells. The review aims to provide a good understanding of
      the new pattern of cancer treatment and key concerns for designing nanomedicine
      of synergistic combinations for cancer therapy.

PMID- 30277133
TI  - Bioformulative concepts on intracellular organ specific bioavailability.
AB  - Bioavailability is an ancient but effective terminology by which the entire
      therapeutic efficacy of a drug directly or indirectly relays. Despite considering
      general plasma bioavailability, specific organ/tissue bioavailability will pave
      the path to broad spectrum dose calculation. Clear knowledge and calculative
      vision on bioavailability can improve the research and organ-targeting
      phenomenon. This article comprises a detailed introduction on bioavailability
      along with regulatory aspects, kinetic data and novel bioformulative approaches
      to achieve improved organ specific bioavailability, which may not be readily
      related to blood plasma bioavailability.

PMID- 30277134
TI  - Sodium alginate capsulation increased brain delivery of probucol and suppressed
      neuroinflammation and neurodegeneration.
AB  - AIM: To enhance the bioavailability and brain uptake of probucol and examine
      whether it attenuates neuroinflammation and neurodegeneration by utilizing a
      sodium alginate nanoencapsulation technique. MATERIALS & METHODS: Wild-type mice
      were given either low-fat standard chow, high-fat (HF) diet to induce
      neuroinflammation and neurodegeneration, HF diet supplemented with nanocapsuled
      probucol at a concentration of 0.1% (w/w), HF diet supplemented with
      noncapsulated probucol at the same concentration of 0.1%, or HF diet supplemented
      with noncapsulated probucol at higher concentration (1%) for 24 weeks. RESULTS &
      CONCLUSION: The nanoencapsulation increased the plasma and brain concentration of
      probucol significantly compared with the mice that was given the same dosage of
      probucol without capsulation, and significantly suppressed the neuroinflammation
      and neurodegeneration.

PMID- 30277136
TI  - Industry update covering June 2018.

PMID- 30277135
TI  - Long-lasting immunosuppressive effects of tacrolimus-loaded micelle NK61060 in
      preclinical arthritis and colitis models.
AB  - AIM: Tacrolimus (TAC) is an important drug for inflammatory diseases. However,
      TAC has several limitations, such as variable trough concentrations among
      individuals and a high medication frequency. In this study, we created NK61060, a
      novel micellar TAC formulation, to circumvent these disadvantages. MATERIALS &
      METHODS: Immunosuppressive activity of NK61060 was determined in the collagen
      induced arthritis rat model, mannan-induced arthritis mouse model and dextran
      sodium sulfate-induced colitis mouse model. The pharmacokinetics and toxicology
      of NK61060 were evaluated in those models. RESULTS: In arthritis and colitis
      models, NK61060 exhibited superior immunosuppressive activity compared with that
      of TAC. Pharmacokinetic and toxicological analyses indicated that NK61060 had a
      wider safety margin and could be administered at a reduced medication frequency.
      CONCLUSION: NK61060 mitigates the trough concentration variability and the
      medication frequency and it may be a safer and more effective option for use in
      clinical settings. Further studies are needed to determine its clinical
      usefulness.

PMID- 30277137
TI  - Emerging therapeutic nanotechnologies in pancreatic cancer: advances, risks and
      challenges.

PMID- 30277138
TI  - Formulation of RNA interference-based drugs for pulmonary delivery: challenges
      and opportunities.
AB  - With recent advances in the field of RNAi-based therapeutics, it is possible to
      make any target gene 'druggable', at least in principle. The present review
      focuses on aspects critical for pulmonary delivery of formulations of nucleic
      acid-based drugs. The first part introduces the therapeutic potential of RNAi
      based drugs for the treatment of lung diseases. Subsequently, we discuss
      opportunities for formulation-enabled pulmonary delivery of RNAi drugs in light
      of key physicochemical properties and physiological barriers. In the following
      section, an overview is included of methodologies for imparting inhalable
      characteristics to nucleic acid formulations. Finally, we review one of the
      bottlenecks in the early preclinical testing of inhalable nucleic acid-based
      formulations, in other words, devices suitable for pulmonary administration of
      powder-based formulations in rodents.

PMID- 30277139
TI  - Preface.

PMID- 30277140
TI  - Systematic review on anti-diabetic properties of chalcones.
AB  - The use of anti-diabetic drugs has been increasing worldwide and the evolution of
      therapeutics has been enormous. Still, the currently available anti-diabetic
      drugs do not present the desired efficacy and are generally associated with
      serious adverse side effects. Thus, entirely new interventions, addressing the
      underlying etiopathogenesis of type 2 diabetes mellitus, are required. Chalcones,
      secondary metabolites of terrestrial plants and precursors of the flavonoids
      biosynthesis, have been used for a long time in the traditional medicine due to
      their wide-range of biological activities, from which the anti-diabetic activity
      stands out. This review systematizes the information found in literature about
      the anti-diabetic properties of chalcones, in vitro and in vivo. Chalcones are
      able to exert these properties by acting in different therapeutic targets:
      dipeptidyl peptidase 4 (DPP-4); glucose transporter type 4 (GLUT4), sodium
      glucose cotransporter 2 (SGLT2), alpha-amylase, alpha-glucosidase, aldose
      reductase (ALR), protein tyrosine phosphatase 1B (PTP1B), peroxisome proliferator
      activated receptor-gamma (PPARgamma) and adenosine monophosphate (AMP)-activated
      protein kinase (AMPK). Chalcones are, undoubtedly, promising anti-diabetic
      agents, and some crucial structural features as already been established. From
      the structure-activity relationships analysis, it can generally be stated that
      the presence of hydroxyl, prenyl and geranyl groups in their skeleton improves
      their activity on the evaluated antidiabetic targets.

PMID- 30277141
TI  - Bio-polymer Substrates in Buccal Drug Delivery: Current Status and Future Trend.
AB  - BACKGROUND: This paper provides a critical review of biopolymer-based substrates,
      especially the cellulose derivatives, for their application in buccal drug
      delivery. Drug delivery to the buccal mucous has the benefits of immobile muscle,
      abundant vascularization and rapid recovery, but not all the drugs can be
      administered through the buccal mucosa (e. g., macromolecular drugs), due to the
      low bioavailability caused by their large molecular size. This shortfall inspired
      the rapid development of drug-compounding technologies and the corresponding
      usage of biopolymer substrates. METHODS: Cellulose derivatives have been
      extensively developed for drug manufacturing to facilitate its delivery. We
      engaged in structured research of cellulose-based drug compounding technologies.
      We summarized the characteristic cellulose derivatives which have been used as
      the biocompatible substrates in buccal delivery systems. The discussion of the
      potential use of the rapidly-developed nanocellulose (NC) is also notable in this
      paper. RESULTS: Seventy-eight papers were referenced in this perspective paper
      with the majority (sixty-five) published later than 2010. Forty-seven papers
      defined the buccal drug delivery systems and their substrates. Fifteen papers
      outlined the properties and applications of cellulose derivatives. Nanocellulose
      was introduced as a leading edge of nanomaterial with sixteen papers highlighted
      its adaptability in drug compounding for buccal delivery. CONCLUSION: The
      findings of this perspective paper proposed the potential use of cellulose
      derivatives, the typical kind of biopolymers, in the buccal drug delivery system
      for promoting the bioavailability of the macromolecular drugs. Nanocellulose (NC)
      in particular was proposed as an innovative bio-binder/carrier for the controlled
      release of drugs.

PMID- 30277142
TI  - A Review: The Anti-inflammatory, Anticancer, Antibacterial Properties of Four
      Kinds of Licorice Flavonoids Isolated from Licorice.
AB  - Plants have always been an important source of medicines for humans, and licorice
      is a very significant herb in the development of humans. As a traditional herb,
      it is widely cultivated in China, Japan, Russia, Spain, and India. With the
      development of organic chemistry and biochemistry, various chemical ingredients
      extracted from licorice have been studied and identified. Among them, many
      chemical components were considered to have strong pharmacological activities,
      such as anti-inflammatory, anti-ulcer, antibacterial, anticancer and so on. Based
      on those reports, licorice has attracted the attention of many researchers in
      recent years, and they are devoted to discovering the active ingredients and
      mechanism of action of active compounds. Licorice flavonoids are one of the main
      extracts of licorice root and stem, and has many potential biological properties.
      This paper aims to summarize the four kinds of licorice flavonoids, including
      liquiritigenin, isoliquiritigenin, licochalcone (including licochalcone A and
      licochalcone B) and glabridin, about their biological activities of anti
      inflammatory, anticancer, antibacterial.

PMID- 30277143
TI  - Cordycepin in Anticancer Research: Molecular Mechanism of Therapeutic Effects.
AB  - BACKGROUND: Cordycepin is a nucleotide analogue from Cordyceps mushrooms, which
      have a notable place in traditional medicine. OBJECTIVE: In this review article,
      we have discussed the recent findings on the molecular aspects of cordycepin
      interactions with its recognized cellular targets, and possible mechanisms of its
      anticancer activity. METHOD: We have explored databases like pubmed, google
      scholar, scopus and web of science for the update information on cordycepin and
      mechanisms of its anticancer activity, and reviewed in this study. RESULTS:
      Cordycepin has been widely recognized for its therapeutic potential against many
      types of cancers by various mechanisms. More specifically, cordycepin can induce
      apoptosis, resist cell cycle and cause DNA damage in cancer cells, and thus kill
      or control cancer cell growth. Also cordycepin can induce autophagy and modulate
      immune system. Furthermore, cordycepin also inhibits tumor metastasis. Although
      many success stories of cordycepin in anticancer research in vitro and in animal
      model, and there is no successful clinical trial yet. CONCLUSION: Ongoing
      research studies have reported highly potential anticancer activities of
      cordycepin with numerous molecular mechanisms. The in vitro and in vivo success
      of cordycepin in anticancer research might influence the clinical trials of
      cordycepin, and this molecule might be used for development of future cancer
      drug.

PMID- 30277144
TI  - Flavonoids as P-gp inhibitors: a systematic review of SARs.
AB  - P-glycoprotein, also known as ABCB1 in the ABC transporter family, confers the
      simultaneous resistance of metastatic cancer cells towards various anticancer
      drugs with different targets and diverse chemical structures. The exploration of
      safe and specific inhibitors of this pump has always been the pursuit of
      scientists for the past four decades. Naturally occurring flavonoids as
      benzopyrone derivatives were recognized as a class of nontoxic inhibitors of P
      gp. The recent advent of synthetic flavonoid dimer FD18, as a potent P-gp
      modulator in reversing multidrug resistance both in vitro and in vivo,
      specifically targeted the pseudodimeric structure of the drug transporter and
      represented a new generation of inhibitors with high transporter binding affinity
      and low toxicity. This review concerned the recent updates on the structure
      activity relationships of flavonoids as P-gp inhibitors, the molecular mechanisms
      of their action and their ability to overcome P-gp-mediated MDR in preclinical
      studies. It had crucial implications on the discovery of new drug candidates that
      modulated the efflux of ABC transporters and also provided some clues for the
      future development in this promising area.

PMID- 30277145
TI  - Insight into T-type calcium channel structure, function and modulation.
AB  - Low voltage-activated (LVA) T-type calcium channels are characterized by
      transient current and low threshold spikes (LTS), which in turn triggers neuronal
      firing and oscillatory behavior. Combined with their preferential localization in
      dendrites and their specific "window current", T-type calcium channels are
      considered to be key players in signal amplification and synaptic integration.
      Assisted by the developing pharmacological tools, the structural determinants in
      channel gating and kinetics, as well as novel physiological and pathological
      functions of T-type calcium channels are rapidly being uncovered. In this review,
      we provide an overview of structural determinants in T-type calcium channels,
      their involvement in disorders and diseases, the development of novel channel
      modulators, as well as structure-activity relationship (SAR) studies that lead to
      rational drug design.

PMID- 30277146
TI  - Autologous blood for conjunctival autograft fixation in primary pterygium
      surgery: A systematic review and meta-analysis.
AB  - OBJECTIVE: To perform a systematic review and meta-analysis of randomized
      controlled trials comparing the efficacy and complications of autologous blood
      versus using fibrin glue and surgical sutures for conjunctival autograft fixation
      in primary pterygium surgery. DESIGN: Systematic review with quantitative meta
      analysis. METHODS: Four authentic databases have been searched using relevant
      keywords. Eligible studies were obtained, and their data were extracted into an
      online form. Analysis was done using Review Manager for windows. Dichotomous
      outcomes were reported as risk ratio, while continuous data were reported as mean
      difference. RESULTS: Seven studies were included in the analysis. Most of
      included studies were of moderate quality according to Cochrane Risk of Bias
      assessment tool. There was no difference between the three techniques in
      recurrence rates (Risk Ratio (RR) 0.80, 95% CI [0.45 to 1.44], p= 0.46). Graft
      retraction and displacement were more profound in the autologous blood group vs
      fibrin glue and suture groups (RR 3.22, 95% CI [1.48 to7.02], p= 0.003) and (RR
      5.27, 95% CI [2.24 to 12.38], p> 0.001) respectively. In terms of operative time,
      fibrin glue took shorter while suturing took longer time compared to blood
      coagulum (Mean Difference (MD) =1.57, 95% CI [0.90, 2.25], p> 0.00001) and (MD 
      20.47, 95% CI [-38.05 to -2.88], p =0.02). CONCLUSIONS: Autologous blood for
      conjunctival autograft fixation in primary pterygium surgery was associated with
      lower graft stability than fibrin glue or sutures. However, it did not account
      for higher recurrence rates than the fibrin glue or sutures. Patient satisfaction
      and postoperative symptoms are relatively better in the blood coagulum group than
      the other techniques. The overall quality of evidence is low. Further well
      designed randomized controlled trials are still needed.

PMID- 30277147
TI  - Complementary functional strategy for modulation of human gut microbiota.
AB  - BACKGROUND: Two pathologies commonly associated with gut microbiota dysbiosis are
      type 2 diabetes and cardiovascular diseases. A disturbance in microbial balance
      translates into the occurrence of degenerative dysfunctions that are also
      associated with other pathologies, such as obesity, colon cancer. METHODS: Thus,
      the aim of this review was to present the significant findings related to human
      microbiome modulation via the prebiotic effects of wild edible mushrooms as a
      complementary strategy to modern treatment. RESULTS: Since diet and medication
      are two important causes of microbiome fingerprint modifications, new
      complementary and alternative methods can include wild edible mushrooms, which
      serve as functional products, given their properties in modulating the microbial
      pattern at the colon level. The metagenomic study has enabled the identification
      of some competitive microbiological and biochemical biomarkers which allow the
      development of innovative strategies in controlling microbial disbalance from
      human gut. CONCLUSION: Certain mushroom species have been approaching and their
      effects on the microbiota fingerprint of two major target groups are highlighted.

PMID- 30277148
TI  - Current status on the effect of diterpenes on hepatic system.
AB  - BACKGROUND: Complication in the hepatic system is a major concern for human
      being. To control and keep the hepatic system healthy, a number of measures,
      including drug treatments are considered. Diterpenes are essential oils have
      promising antioxidant and cytotoxic properties along with their genotoxic and
      mutagenic effects. These agents are good targets for health promotion, especially
      in the light of their potential of organo-protectivity. METHODS: We searched in
      the databases, PUBMED and SCIENCE DIRECT from June 2011 to June 2016 for
      publishing evidence on diterpenes and their effects on hepatic system. After
      sorting the data, activity-wise findings are discussed in this current article.
      RESULTS: The results suggest that diterpenes have hepatoprotectivity property via
      antioxidant and anti-inflammatory, antimicrobial, anticancer/antitumor,
      hypolipidemic, anti-apoptosis, autophagic, anti-metastasize, anti-proliferating,
      anti-fibrosis as well as receptor and serum biomarkers mediated pathways. On the
      other hand, hepatoxic effects of diterpenes are also accounted with cytotoxicity,
      apoptotic cell death and down-regulatory effects on cytochrome P450 systems.
      CONCLUSION: A number of important diterpenes have been reported in the
      literatures that act on the hepatic system. Some of them exert toxic effects on
      the liver, especially in rodent model. Hence, more extensive researches are
      recommended that will highlight their mechanism of action on the liver.

PMID- 30277149
TI  - Protective mechanisms of Butyrate on Inflammatory Bowel Disease.
AB  - Inflammatory bowel disease (IBD) is a multifactorial chronic disease, commonly
      associated with alteration in the composition and function of gut microbiota.
      This process can lead to a decreased production of short chain fatty acids
      (SCFAs) by the gut microbiota, mainly butyrate, which is an important
      immunomodulatory molecule in the intestine. Butyrogenic bacteria normally
      produces butyrate through carbohydrate fermentation or amino acids degradation
      pathways. This molecule plays an important protective role in intestinal
      homeostasis acting in both adaptive immunity and innate immunity. This review
      summarizes the current knowledge about the role of butyrate on the development of
      IBD and the protective mechanisms of this metabolite on the intestinal mucosa and
      the whole body, as reported by in vitro and in vivo studies. Thus, butyrate can
      regulate the activation of regulatory T cells, increasing the acetylation of
      histones and decreasing the activation of NF-kappaB. In addition, it can also
      stimulate the mucus production from epithelial cells and the rearrangement of
      tight junction proteins.

PMID- 30277150
TI  - A survey for predicting enzyme family classes using machine learning methods.
AB  - Enzymes are proteins that act as biological catalysts to speed up cellular
      biochemical processes. According to their main Enzyme Commission (EC) numbers,
      enzymes are divided into six categories: EC-1: oxidoreductase; EC-2: transferase;
      EC-3: hydrolase; EC-4: lyase; EC-5: isomerase and EC-6: synthetase. Different
      enzymes have different biological functions and acting objects. Therefore,
      knowing which family an enzyme belongs to can help infer its catalytic mechanism
      and provide information about the relevant biological function. With the large
      amount of protein sequences influxing into databanks in the post genomics age,
      the annotation of family for an enzyme is very important. Since the experimental
      methods are cost ineffective, bioinformatics tool will be a great help for
      accurately classifying the family of the enzymes. In this review, we summarized
      the application of machine learning methods in the prediction of enzyme family
      from different aspects. We hope that this review will provide insights and
      inspirations for the researches on enzyme family classification.

PMID- 30277151
TI  - Alzheimer's Disease: Physical Activities as an Effective Intervention Tool - A
      Mini-Review.
AB  - BACKGROUND: There are a few risk factors which definitely have an impact on the
      development of Alzheimer's disease (AD). Those include genetics, gender, age,
      diabetes, head injuries, and lifestyle. Physical activity together with healthy
      diet is part of people's lifestyle. At present there exist several research
      studies showing that the physical activities can be a good intervention tool in
      the delay of cognitive decline in AD. OBJECTIVE: The aim of this study is to
      discuss a relationship between the physical activities and the delay and/or
      maintenance of cognitive decline in AD and the types of physical activities which
      are especially suitable for this delay. METHODS: The method of this review study
      consists of a method of literature review analysing the data contained in the
      world's prestigious scientific databases: PubMed, Springer, Web of Science and
      Scopus in the period of 2010 - 2015. In addition, a method of comparison of
      different research studies discussing various aspects and factors of the
      correlation of physical activities and AD is used. RESULTS: The findings of this
      review confirm that in most cases physical activities have a positive effect on
      the improvement of cognitive decline in AD. CONCLUSION: Although physical
      activities seem to be beneficial for people with AD, more convincing results,
      particularly in the area of specific types of exercises and their impact on
      slowing down the cognitive decline, respectively AD, are needed.

PMID- 30277152
TI  - Effect of the Interaction Between Hypertension and Cerebral White Matter Changes
      on the Progression of Alzheimer Disease.
AB  - BACKGROUND: Cerebrovascular pathologies and hypertension could play a vital role
      in Alzheimer disease (AD) progression. However, whether cerebrovascular
      pathologies and hypertension accelerate the AD progression through an independent
      or interaction effect is unknown. OBJECTIVE: To investigate the effect of the
      interactions of cerebrovascular pathologies and hypertension on AD progression.
      METHOD: A retrospective longitudinal study was conducted to compare AD courses in
      patients with different severities of cerebral White Matter Changes (WMCs) in
      relation to hypertension. Annual comprehensive psychometrics were performed. WMCs
      were rated using a rating scale for Age-related WMCs (ARWMC). RESULTS: In total,
      278 patients with sporadic AD were enrolled in this study. The mean age of the
      patients was 76.6 +/- 7.4 years, and 166 patients had hypertension. Among AD
      patients with hypertension, those with deterioration in clinical dementia rating
      sum of box (CDR-SB) and CDR had significantly severe baseline ARWMC scales in
      total (CDR-SB: 5.8 vs. 3.6, adjusted P = 0.04; CDR: 6.4 vs. 4.4, adjusted P =
      0.04) and frontal area (CDR-SB: 2.4 vs. 1.2, adjusted P = 0.01; CDR: 2.4 vs. 1.7,
      adjusted P < 0.01) compared with those with no deterioration in psychometrics
      after adjustment for confounders. By contrast, among AD patients without
      hypertension, no significant differences in ARWMC scales were observed between
      patients with and without deterioration. CONCLUSION: The effect of
      cerebrovascular pathologies on AD progression between those with and without
      hypertension might differ. An interaction but not independent effect of
      hypertension and WMCs on the progression of AD is possible.

PMID- 30277153
TI  - Conventional versus natural alternative treatments for leishmaniasis :a review.
AB  - Leishmaniasis is a neglected disease caused by protozoan belonging to the
      Leishmania genus. There are at least 16 pathogenic species for humans that are
      able to cause different clinical forms, such as cutaneous or visceral
      leishmaniasis. In spite of the different species and clinical forms, the
      treatment is performed with few drug options that, in most cases, are considered
      outdated. In addition, patients under classical treatment show serious side
      effects during drug administration, moreover parasites are able to become
      resistant to medicines. Thus, it is believed and well accepted that is urgent and
      necessary to develop new therapeutic options to overpass these concerns about
      conventional therapy of leishmaniasis. The present review will focus on the
      efficacy, side effects and action mechanism of classic drugs used in the
      treatment of leishmaniasis, as well as the importance of traditional knowledge
      for directing a rational search toward the discovery and characterization of new
      and effective molecules (in vivo assays) from plants to be used against
      leishmaniasis.

PMID- 30277154
TI  - Design, Synthesis and Antileishmanial Activity of Naphthotriazolyl-4-
      Oxoquinolines.
AB  - BACKGROUND: Leishmaniasis is a neglected public health problem caused by several
      protozoanspecies of the genus Leishmania. The therapeutic arsenal for treating
      leishmaniasis is quite limited, raising concerns about the occurrence of
      resistant strains. Furthermore, most of these drugs were developed more than 70
      years ago and suffer from poor efficacy and safety and are not well adapted to
      the needs of patients. Therefore, research on novel natural or synthetic
      compounds with antiparasitic activity is urgently needed. In this paper, we
      evaluated the effect and the mechanism of action of naphthotriazolyl-4
      oxoquinolines on promastigotes and intracellular amastigotes of Leishmania
      amazonensis. MATERIALS AND METHODS: The naphthotriazolyl-4-oxoquinoline
      derivatives were obtained in good to moderate yields via the [3+2] cycloaddition
      reaction between 1,4-naphtoquinone and azido-4- oxoquinoline derivatives. HMPA at
      100 degrees C was established as the best solvent and temperature condition for
      this reaction. The structures of the compounds were confirmed by spectral
      analyses (infrared spectroscopy, one- and two-dimensional 1H and 13C NMR
      spectroscopy, and high-resolution mass spectrometry). The compounds exhibited
      promising activities with IC50 values ranging from 0.7 to 2.0 uM against
      intracellular amastigotes of Leishmania amazonensis. The most selective compound
      was the Npentyl- substituted derivative, which showed a Selectivity Index (SI) of
      8.6, making it less toxic than pentamidine (SI 4.5). RESULTS: Our results
      demonstrated that all compounds, except the N-propyl-substituted derivative,
      induce ROS production by parasites early in the culture. As a proof of concept,
      we demonstrated that the most selective compound was able to interfere with
      sterol biosynthesis in L. amazonensis. CONCLUSION: The naphthotriazolyl-4
      oxoquinoline derivatives were obtained in good to moderate yields. These
      conjugates have potent in vitro antileishmanial activity involving at least two
      different mechanisms of action, making them promising lead compounds for the
      development of new therapeutic alternatives for leishmaniasis.

PMID- 30277155
TI  - Giardiasis: characteristics, pathogenesis and new insights about treatment.
AB  - Giardia intestinalis infection causes enterocytes damage and loss of brush border
      of the epithelial cells of the intestine that leads in shortening of microvilli
      and altered epithelial barrier function. This pathology curses with aqueous
      diarrhoea, steatorrhea, nausea, abdominal pain, vomiting and weight loss.
      However, most infections are either asymptomatic. The main consequence of Giardia
      colonization is nutrients malabsorption. Several families of drugs with good
      efficacy are used for Giardia treatment, but sometime dosing regimens are
      suboptimal and emerging resistance begins to question their clinical value.
      Moreover, some of these drugs can cause side effects that result in patient
      discomfort and low adherence to the treatment. This paper reviews the drugs
      currently used for the treatment against Giardia: the mechanism of action, the
      efficacy, the normal dosing, side effects and in vitro and clinical studies. In
      addition, new therapies against Giardia such as those based on phytochemicals,
      Lactobacillus and nanotechnology are collected in this paper, trying to find the
      ideal treatment for this disease with maximum efficacy and minimum adverse
      effects.

PMID- 30277156
TI  - Natural products for vulvovaginal candidiasis treatment: evidence from clinical
      trials.
AB  - BACKGROUND: Candida albicans is an opportunistic yeast that causes more than 90%
      of all vulvovaginal infections. Because of inherently resistant to antifungals
      drugs such as azole derivatives, the search for anti-Candida albicans agents with
      new pharmacological targets is considered as the main therapeutic strategy to
      prevent and treat these type of infections. In this context, products of natural
      origin are a promising source of compounds with antifungal activity. OBJECTIVE:
      The current review analyzes clinical evidence on the effectiveness of natural
      products in the vulvovaginal Candida albicans infections. METHOD: A literature
      review in the electronic databases PubMed, Google Scholar, Cochrane Library Plus,
      Web of Science, Latin American and Caribbean Literature on Health Sciences
      (Lilacs) and Scientific Electronic Library Online (SciELO) using the search terms
      "natural products", "phytotherapy", "vulvovaginal candidiasis" and "clinical
      trials" together with the Boolean term 'AND' was performed. English, Spanish and
      French articles without restriction of date of publication were considered.
      RESULTS: A total of 13 clinical trials (most of them randomized clinical trials
      which used azoles as control group) that evaluate the anti-Candida activity of a
      total of 11 different natural products (i.e. Zataria multiflora essential oils,
      Ageratina pichinchensis and Solanum nigrescens extracts and saponins from Solanum
      chrysotrichum, among others) against vulvovaginitis have been included in the
      current review. CONCLUSION: Because of the few clinical trials it is difficult to
      establish a consistent conclusion about the effectiveness of natural products in
      the prevention and treatment of vulvovaginitis caused by Candida albicans. Future
      studies should be aimed at evaluating new natural products as well as conducting
      more clinical research with promising natural substances already investigated in
      clinical trials.

PMID- 30277157
TI  - Paracoccidioides spp. and Histoplasma capsulatum: current and new perspectives
      for diagnosis and treatment.
AB  - The thermally-dimorphic systemic fungal group includes several important human
      pathogens: Blastomyces dermatitidis, Coccidioides immitis and C. posadasii,
      Histoplasma capsulatum, Paracoccidioides brasiliensis, P. lutzii, and Talaromyces
      (Penicillium) marneffei. They usually are geographically restricted and have
      natural habitats in soil or in plants, and when fungal propagules invade
      mammalian host by inhalation, they initiate an inflammatory reaction that can
      result in self-resolution of the infection or cause an acute or chronic disease.
      In the setting of the AIDS pandemic and the developments in modern medicine, such
      as immunosuppressive therapy in cancer surgery patients and in transplantation
      and autoimmune diseases, the incidence of endemic mycoses has progressively
      increased. Another important factor of the increased incidence of systemic
      mycoses in certain regions is the progressive devastation of tropical and
      subtropical forests. In this review, we focus on two of the most important
      systemic mycoses: paracoccidioidomycosis and histoplasmosis, and their major
      characteristics in epidemiology, clinical aspects and laboratorial diagnosis.

PMID- 30277158
TI  - Treatment of toxoplasmosis and neosporosis in farm ruminants: state of knowledge
      and future trends.
AB  - Toxoplasmosis and neosporosis are closely related protozoan diseases that lead to
      important economic impacts in farm ruminants. Toxoplasma gondii infection mainly
      causes reproductive failure in small ruminants and is a widespread zoonosis,
      whereas Neospora caninum infection is one of the most important causes of
      abortion in cattle worldwide. Vaccination has been considered the most economic
      measure for controlling these diseases. However, despite vaccine development
      efforts, only a live-attenuated T. gondii vaccine has been licensed for
      veterinary use, and no promising vaccines against neosporosis have been
      developed; therefore, vaccine development remains a key goal. Additionally, drug
      therapy could be a valuable strategy for disease control in farm ruminants, as
      several drugs that limit T. gondii and N. caninum proliferation and dissemination
      have been evaluated. This approach may also be relevant to performing an initial
      drug screening for potential human therapy for zoonotic parasites. Treatments can
      be applied against infections in adult ruminants to minimize the outcomes of a
      primo-infection or the reactivation of a chronic infection during gestation or in
      newborn ruminants to avoid infection chronification. In this review, the current
      status of drug development against toxoplasmosis and neosporosis in farm
      ruminants is presented, and in an effort to promote additional treatment options,
      prospective drugs that have shown efficacy in vitro and in laboratory animal
      models of toxoplasmosis and neosporosis are examined.

PMID- 30277159
TI  - Extracellular vesicles and insulin resistance: a potential interaction in
      vascular dysfunction.
AB  - Insulin resistance plays a key role in cardiovascular complications associated
      with diabetes mellitus and hypertensive disorders. In states of insulin
      resistance several circulating factors may contribute to a defective insulin
      sensitivity in different tissues, including the vasculature. One of these factors
      influencing the vascular insulin resistance are the extracellular vesicles. The
      extracellular vesicles include exosomes, microvesicles, and apoptotic bodies
      which are released to the circulation by different vascular cells. Since the
      cargo of extracellular vesicles seems to be altered in metabolic complications
      associated with insulin resistance, these vesicles may be candidates contributing
      to vascular insulin resistance. Despite of the studies linking insulin resistance
      signalling pathways with the vascular effect of extracellular vesicles, the
      involvement of these structures in vascular insulin resistance is a phenomenon
      that remains unclear.

PMID- 30277160
TI  - Herbal Drug Use In Sickle Cell Disease Management; Trends And Perspectives In Sub
      Saharan Africa.
AB  - Introduction Nigeria has the largest burden of Sickle Cell Disease (SCD) with
      estimated 100,000 new born affected annually. SCD is a hemoglobin (Hb) disorder
      with the major form resulting from the substitution of a polar glutamate (Glu) by
      non-polar Valine (Val) in an invariant region, of Hb? chain-subunit. Species of
      Hb found in sickle cell trait are HbA and HbS at a 60:40 proportion, in SCD only
      HbS, in the HbC disease only HbC, and in the SC disease it's HbS and HbC in a
      50:50 equal proportion. Objective This paper reviews herbal medicines usagein sub
      Saharan Africa (sSA) to ameliorate the crisis associated with SCD.The model Hb
      tetramer, suggest a higher membrane affinity of HbS and HbC, promoting
      dehydration of RBCs, with concomitant in vivo crystallization. Some drawback
      using these herbal drugs includes; poorbioavailability and the lack of proper
      pharmacovigilance monitoring procedures arising from weak governance structure
      combined with under reporting of herbal usage tophysicians was also discussed.
      Probable epigenetic loci that could be targeted using phytomedicines for
      effective SCD management are discussed. Methods Using search engines, several
      databases including Google scholar, PubMed, Academic Resource Index were utilized
      to source for relevant publications/literatures. The protein coordinates for the
      Hb tetramer were obtained from the Protein Data Bank (PDB). Conclusion
      Manipulation of epigenetics to achieve better SCDmanagement involvescareful
      thinking.Herein, we discuss some epigenetic interactionsthat could be putatively
      tweaked with a view to enhancing solublebioactive small molecular components with
      potential to reactivate gamma -globin genes, boosting immune response in-patient
      with SCD.

PMID- 30277161
TI  - The impact of depressive symptoms on quality of life of patients with type 2
      diabetes in Jazan region, KSA.
AB  - PURPOSE: The purpose of this study is to determine the impact of depressive
      symptoms on the quality of life of type 2 diabetes patients (T2DM). METHOD: A
      cross sectional study of 332 T2DM patients aged >=18 years living in Jazan region
      of Saudi Arabia. Validated questionnaire was used for demographic and disease
      characteristics. Depressive symptoms of the participants were assessed using the
      Patient Health Questionnaire (PHQ-9). The Quality of Life Enjoyment and
      Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) was utilized to assess the
      degree of life enjoyment and satisfaction. RESULTS: Depressive symptoms were met
      in 34.7% (112) of the total participants. The overall sense of wellbeing (mean
      3.23, P .value 0.000), physical (mean 3.37, P .value 0.003), psychosocial (mean
      2.99 P .value 0.000) and social domains (mean 3.53, P .value 0.000) of quality of
      life were significantly reduced in T2DM patients with depressive symptoms.
      CONCLUSION: The impact of depressive symptoms on quality of life of T2DM patients
      was more significant than the impact of diabetes alone. Symptoms of depression
      reduce the individual coping and hence reduce functioning. This study emphases
      the vital importance of an integrated holistic approach that addresses both the
      practical and emotional issues in diabetes care.

PMID- 30277162
TI  - Myxedema Heart Disease: A rare disease entity. Case report and brief review of
      the literature.
AB  - BACKGROUND: Myxedema heart disease is an extremely rare disease entity and should
      be suspected in patients with unexplained heart failure refractory to
      conventional treatment. Myxedema coma with co- existent heart disease is not well
      known and very few cases have been reported. CONCLUSION: Here we present an
      interesting case of myxedema coma with severe valvular cardiomyopathy followed by
      a concise review of the literature with special emphasis on epidemiology,
      pathophysiology, diagnosis and therapeutic modalities.

PMID- 30277163
TI  - Anaemogenic, Obesogenic And Thermogenic Potentials Of Graded Doses Of Monosodium
      Glutamate Sub-Acutely Fed To Experimental Wistar Rats.
AB  - BACKGROUND: Monosodium glutamate (MSG) is one of the most commonly used food
      additives for the enhancement of food taste and flavour. There are several
      conflicting reports of toxicity or otherwise safety of the compound, which raises
      a growing concern regarding the safety of monosodium glutamate as food additive.
      OBJECTIVE: In the present study, we sought to investigate the effect of
      monosodium glutamate on body weight, feed consumption, body temperature and some
      haematological parameters. METHODOLOGY: Twenty adult Wistar rats divided into
      four groups of five rats each were used for the study. Rats in groups 1, 2 and 3
      were given feed thoroughly mixed with 3, 6 and 9 g of monosodium glutamate
      respectively for 14 days, while rats in group 4 (Control) were given only the
      feed for the same period of time. Body weight, temperature, feed consumption, and
      some haematological parameters were measured before the addition of the compound
      to the feed and thereafter for every 2 days for a period of 14 days. RESULTS: Our
      findings indicated significant changes (P < 0.05) in the red blood cells (RBC)
      count, packed cell volume (PCV), as well as body temperature in all the treated
      groups compared to the control group. The result also revealed a significant dose
      dependent increase in body weight in the groups treated with 6 and 9 g of
      monosodium glutamate compared to the control, the body weight correlated
      positively with the duration of monosodium glutamate consumption. CONCLUSION: The
      current data suggest that consumption of high doses/quantity of monosodium
      glutamate for a long duration of time could lead to anaemia due to decrease in
      red blood cell count and packed cell volume and obesity resulting from increase
      in body.

PMID- 30277164
TI  - Safety of Vinflunine in patients with advanced urothelial carcinoma refractory to
      platinum-based chemotherapy: a prospective pilot study.
AB  - BACKGROUND: Several single chemotherapeutic agents have been evaluated as second
      line treatment of advanced urothelial carcinoma. Despite encouraging efficacy
      outcomes, toxicity has often led to dose modifications or discontinuation. We
      aimed to assess safety of vinflunine in a particular population of advanced
      transitional cell carcinoma of urothelium (TCCU), that were exposed to previous
      toxicity of chemotherapy. METHODS: This is an open-label, prospective, single
      center pilot study to evaluate the response rate and safety profile of vinflunine
      in patients with advanced TCCU. It was planned to enroll 25 evaluable patients.
      Eligible patients are those with progressive disease after first line platinum
      based regimen for advanced or metastatic disease. RESULTS: The study was
      prematurely closed due to two sudden deaths that were judged by the review board
      as treatment-related. Only ten patients were evaluated and received at least one
      cycle of vinflunine. All but one were male and seven underwent radical surgery.
      Eight had a distant metastasis (mainly lung and/or liver). Disease control rate
      was 40%, four patients had a partial response with median duration of response of
      3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There
      were three serious adverse events namely two sudden deaths and one grade 4
      thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all
      grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%).
      Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who
      achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy.
      CONCLUSION: The activity of vinflunine in advanced urothelial carcinoma came at
      the expense of its safety. The use of vinflunine has to be limited to selected
      group of patients. However, this is a single institute experience in a limited
      number of patients.

PMID- 30277165
TI  - Biochemical and Pharmacological Applications of Essential Oils in Human Health
      Especially in Cancer Prevention.
AB  - : Background - At present, 'pharmaco-epigenomics' constitutes the hope in cancer
      treatment owing to epigenetic deregulation- a reversible process and playing a
      role in malignancy. OBJECTIVE: Chemotherapy has many limitations like host-tissue
      toxicity, drug resistance. Hence, it is imperative to unearth targets to better
      treat cancer. Here, we intend to repurpose a set of our previously synthesized
      difluorinated propanediones (PR) as histone lysine methyltransferase inhibitors
      (HMTi). METHODS: The cell lines of leukemic origin viz. histiocytic lymphoma
      (U937) and acute T-cell leukemia (JURKAT) were treated with PR-1 to 7 after
      docking studies with active pocket of HMT. The cell cycle analysis, in vitro
      methylation and cell proliferation assays were carried out to delineate their
      physiological role. Results - A small molecule PR-4, at 1 and 10MUM, has shown to
      alter the methylation of histone H3 and H4 in both cell lines. Also, treatment
      shows an increase in G2/M population and a subsequent decrease in the G0/G1
      population in U937. In JURKAT, an increase in both G2/M and S phase population
      was observed. The sub-G1 population showed a steady rise with increase in dose
      and prolonged time intervals in U937 and JURKAT cell lines. In SRB assay, the PR
      showed a cell growth of 42.6 and 53.4% comparable to adriamycin; 44.5 and 53.2%
      in U937 and JURKAT, respectively. The study suggests that PR-4 could emerge as a
      potential HMT inhibitor. Conclusion - The molecule PR-4 could be a lead in
      developing more histone lysine methyltransferases inhibitors with potential to be
      pro-apoptotic agents.

PMID- 30277166
TI  - Spectroscopic and in silico DNA binding studies on the interaction of some new N
      substituted rhodanines with calf-thymus DNA: In vitro anticancer activities.
AB  - BACKGROUND: Cancer is a black spot on the face of humanity in this era of science
      and technology. Thus, the search for new promising anticancer agents continues.
      AIMS: Here we designed and synthesized new N-substituted rhodanines (RD1-7),
      evaluated their multi-spectroscopic interaction with calf thymus DNA, in silico
      and anticancer studies against human breast cancer cell (MDA-MB-231). METHODS:
      Among the compounds, RD5 was found the most potent by MTT assay with IC50 value
      of 17.24MUg/ml. In addition, DNA binding study carried out by UV-Vis and
      fluorescence techniques revealed strong binding affinity of RD1-7 with DNA (Kb in
      the range of 1.5 - 7.4 * 105 M-1). Moreover, theoretical in silico DNA binding
      study supported the experimental DNA binding and anticancer studies. RESULTS: It
      was observed that DNA-compound adducts were stabilized by H-bonding and
      hydrophobic attractions. The compounds preferred to enter into minor grooves of
      DNA. Concisely, the compounds showed encouraging therapeutic properties and,
      therefore, have a promising future and compounds RD1, RD2, and RD5 are promising
      scaffolds for the development of novel anticancer drugs.

PMID- 30277167
TI  - A Brief History of Ebolavirus disease: Paving the Way Forward by Learning from
      the Previous Outbreaks.
AB  - In this review, Ebolavirus disease (EVD) outbreaks have been comprehensively
      reviewed from their beginning until now. It chronologically discusses how each
      outbreak was tackled, national and international actions taken, diagnostic
      methods applied, the infection control procedures were put in place, and the
      lessons learnt from each epidemic for the control of subsequent epidemics. Data
      for this review were obtained from literature published between 1967 and 2016 in
      key medical databases, the official websites of various governmental
      organisations, international public health agencies, and regulatory bodies.
      Despite major developments in the field of EVD, there has been little progress in
      its specific therapy or prevention. Historically, individuals who recovered from
      EVD acted as a source of fresh frozen plasma (containing IgG) that has been used
      to treat other acutely ill patients, however this therapeutic modality has
      limitations due to the risk of transmission of blood-borne infections. With the
      use of advanced and efficient purification methods the incidence of unwanted side
      effects following immune serum therapy has currently been greatly reduced.
      Creation of a safe plasma pool that covers immunoglobulins against all strains of
      EVD is now a research priority. Recommendations on how future EVD outbreaks can
      be better managed have been discussed.

PMID- 30277168
TI  - A review on the characteristic, properties and analytical methods of cefquinome
      sulphate: beta-lactam veterinary drug.
AB  - BACKGROUND: Chemotherapy as a science began within the 1st decade of the
      twentieth century with understanding of the principles of selective toxicity, the
      particular chemical relationships between microorganism pathogens and medicines,
      the event of drug resistance, and also the role of combined medical aid.
      OBJECTIVES: This review aims to highlight the characteristics, specifically the
      pharmacokinetic parameters, and the analytical methods reported in literature for
      the determination of Cefquinome, a fourth generation cephalosporineused to treat
      Gram-positive and Gram-negative caused infections. CONCLUSION: Analysis of such
      drugs, whether used for treatment of human or animal illness, is essential in
      understanding the bioavailability and therapeutic control which will ensure their
      activity and safety.

PMID- 30277169
TI  - Hand hygiene compliance and effectiveness against respiratory infections among
      Hajj pilgrims: a systematic review.
AB  - The role of hand hygiene in the prevention of respiratory tract infections in
      Hajj pilgrims has not been assessed through a focussed systematic review of the
      literature. To this end, a systematic review was undertaken to synthesize the up
      to-date literature on the compliance and effectiveness of hand hygiene among Hajj
      attendees. Major databases, including OVID Medline, were searched by using a
      combination of MeSH terms and text words for potentially relevant articles. Data
      from identified articles were abstracted, quality assessed and combined into a
      summary effect. Twelve observational studies containing data of 6,320 pilgrims
      were included. The compliance of hand washing with non-alcoholic surfactants was
      77.7% (ranged from 31.5% to 90.3% in individual studies) and the compliance of
      hand cleaning with alcoholic products was 44.9% (ranged from 30.7% to 67.4%).
      Education was a key influencer of hand hygiene practice. Only three of six
      studies that assessed the effectiveness of hand hygiene against clinical disease
      found the practice to be effective, and only one of two studies that evaluated
      its effectiveness against a laboratory-confirmed infection found it to be
      effective. This systematic review suggests that hand hygiene using non-alcoholic
      products is generally acceptable among Hajj pilgrims but there is no conclusive
      evidence on its effectiveness.

PMID- 30277170
TI  - Hepatitis B Seroepidemiology in Australia One Decade after Universal Vaccination
      of Infants and Adolescents.
AB  - This study assessed the impact of the staged introduction of universal infant and
      adolescent catch-up hepatitis B vaccination programs on the prevalence of
      immunity and past hepatitis B virus (HBV) infection in targeted cohorts over
      almost a decade in Australia. We compared the prevalence of immunity in relevant
      cohorts of children and adolescents in repeated national serological surveys
      conducted in 1998-99, 2002 and 2007. Residual sera (n =2210) collected
      opportunistically from Australian laboratories in 2007 were tested for antibody
      to hepatitis B surface antigen (anti-HBs) indicating vaccine-induced immunity;
      sera from persons aged 12-29 years with anti-HBs detected (n =386) were then
      tested for hepatitis B core antibody (anti-HBc) to identify past hepatitis B
      infection. In 2007, compared with the baseline period of 1998-99, anti-HBs
      prevalence had increased significantly in all age groups below 24 years, more
      than doubling in target children. Prevalence of anti-HBc was zero in the 12-14
      years and reduces by 71% in those aged 15-19 years. The hepatitis B vaccination
      protected a significant number of targeted adolescents with a modest vaccine
      uptake (57% to 60% nationally). In a setting without incentives or school entry
      requirements, adolescent vaccination coverage was significantly higher when
      delivered by school-based rather than GP-based mechanisms. A cohort of children
      was growing up in Australia with high prevalence of vaccine-induced immunity
      against hepatitis B, providing the best opportunity for controlling HBV infection
      in Australia.

PMID- 30277171
TI  - Immunization status of mothers of children with cerebral palsy in rural
      Bangladesh.
AB  - BACKGROUND: Vaccination is one of the most effective public health tools for
      prevention of infectious diseases, morbidity and disability. Little is known
      about the rate of maternal immunization among mothers of children with cerebral
      palsy (CP), as well as any possible role of maternal immunization in development
      of CP in the newborns. OBJECTIVE: To determine the socio-demographic
      characteristics and self-reported vaccination status of mothers of children with
      CP and compare vaccination coverage in this cohort with national data on
      immunization. The study also aims to assess vaccination status of children with
      CP. METHOD: A subset of the Bangladesh CP Register (BCPR) cohort of women who had
      children with CP were recruited during April 2017 from a community based early
      intervention and rehabilitation program going on in Shahjadpur . Socio
      demographic characteristics and maternal immunization status were assessed using
      a semi-structured questionnaire . The vaccination status of the children was also
      assessed by interviewing mother and observing the BCG marks. All data were
      compared with the corresponding information among general population using
      national vaccination coverage survey reports of the Ministry of Health and Family
      Welfare, Bangladesh. RESULT: Sixty-eight mothers were interviewed of which 17.6%
      mothers reported not receiving any vaccine during pregnancy. Tetanus vaccine was
      most commonly (82.0%) received during pregnancy. Overall coverage for at least
      two doses of tetanus toxoid (TT) among mothers of children with CP was
      significantly lower than the national tetanus coverage (79.4% versus 96.4%,
      p<0.01). Forty two (61.7%) mothers with a child with CP reported to have not
      received tetanus vaccine during their pregnancy compared to only twenty (29.4%)
      mothers with healthy children reported missing tetanus vaccination during their
      pregnancy. This difference was statistically significant (p<0.01). Hepatitis B
      and influenza vaccine were received by mothers of children with CP during
      antenatal period (2 and 6 respectively). CONCLUSION: Immunization among mothers
      of children with CP is significantly poorer than the national coverage. Also, the
      immunization of the children with CP is poorer than the national EPI coverage.
      Our findings reflect that necessity for specific strategies to improve the
      vaccination coverage among mothers of children with disabilities especially CP
      and the children with CP.

PMID- 30277172
TI  - Murine skin-resident gammadeltaT cells impair the immune response to HSV in skin.
AB  - HSV is an important cause of brain infection. Virus entry is often through
      breeches in the skin. gammadeltaT cells play an immunoprotective role in mice
      after corneal, genital or footpad (subcutaneous) HSV infection. Here we report
      that the presence of gammadeltaT cells in murine skin is associated with
      increased severity of herpetic disease, reduced protective cytokine responses and
      increased viral spread from the skin to the sensory ganglia in the zosteriform
      model. gammadeltaT cell-deficient (TCR delta -/-) mice displayed significantly
      decreased herpetic lesion severity after flank HSV infection compared to WT
      C57BL/6 controls at both primary and secondary skin infection sites. Viral titer
      at the primary skin site was similar to WT mice in gammadeltaT cell-deficient
      mice, but was significantly decreased in the ganglia and secondary skin site.
      gammadeltaT cell-deficient mice showed increased Th1 responses by both T cells
      and non-T cells at the primary site, and decreased T-cell Th17 responses and
      immune infiltration at the secondary site. Cytokine responses of epidermal and
      dermal gammadeltaT cells to HSV also differed in WT mice (Th1 in epidermis, and
      Th17 in the dermis), suggesting a functional dichotomy between these two subsets.
      Our data suggest that in contrast to other mouse models of HSV infection, skin
      resident gammadeltaT cells impair the immune response to HSV in skin.

PMID- 30277173
TI  - Novel Compound from Flowers of Moringa oleifera Competently Active against Multi
      Drug Resistant Gram-negative Bacilli.
AB  - BACKGROUND: The need for suitable antibacterial agents effective against Multi
      drug resistant Gram-negative bacteria is acknowledged globally. The present study
      was designed to evaluate possible antibacterial potential of an extracted
      compound from edible flowers of Moringa oleifera. METHODS: Five different
      solvents were used for preparing dried flower extracts. The most effective
      extract was subjected to fractionation and further isolation of the active
      compound with highest antibacterial effect was obtained using TLC, Column
      Chromatography and reverse phase- HPLC. Approaches were made for characterization
      of the isolated compound using FTIR, NMR and Mass spectrometry. Antibacterial
      activity was evaluated according to the CLSI guidelines. RESULTS: One fraction of
      aqueous acetic acid extract of M. oleifera flower was found highly effective and
      more potent than conventional antibiotics of different classes against Multi-drug
      resistant Gram-negative bacilli (MDR-GNB) when compared. The phyto-chemical
      analysis of the isolated compound revealed the presence of hydrogen bonded amine
      and hydroxyl groups attributable to unsaturated amides. CONCLUSIONS: The present
      study provided data indicating a potential for use of the flowers extract of M.
      oleifera in the fight against infections caused by lethal MDR-GNB.
      RECOMMENDATIONS: Aqueous acetic acid flower extract of M. oleifera is effective,
      in-vitro, against Gram-negative bacilli. This finding may open a scope in
      pharmaceutics for the development of new classes of antibiotics.

PMID- 30277174
TI  - Animal models optimise nanoparticles for drug delivery in the treatment of
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) causes significant morbidity and high fatal
      outcome globally. Conventional therapeutic strategies have achieved significant
      improvements for HCC, but they have limitations and are far from ideal. Novel
      nanoparticulate drug delivery systems have recently presented great therapeutic
      potential for HCC. The potential for successful clinical translation of
      formulation strategies can only be evaluated by using appropriate and accurate
      pre-clinical models. This review will provide an overview of different animal
      models of HCC, with a particular emphasis on those applied to assess the
      translational potential for drug nanopharmaceutics.

PMID- 30277175
TI  - Review: Precision nutrition of ruminants: approaches, challenges and potential
      gains.
AB  - A plethora of sensors and information technologies with applications to the
      precision nutrition of herbivores have been developed and continue to be
      developed. The nutritional processes start outside of the animal body with the
      available feed (quantity and quality) and continue inside it once the feed is
      consumed, degraded in the gastrointestinal tract and metabolised by organs and
      tissues. Finally, some nutrients are wasted via urination, defecation and gaseous
      emissions through breathing and belching whereas remaining nutrients ensure
      maintenance and production. Nowadays, several processes can be monitored in real
      time using new technologies, but although these provide valuable data 'as is',
      further gains could be obtained using this information as inputs to nutrition
      simulation models to predict unmeasurable variables in real-time and to forecast
      outcomes of interest. Data provided by sensors can create synergies with
      simulation models and this approach has the potential to expand current
      applications. In addition, data provided by sensors could be used with advanced
      analytical techniques such as data fusion, optimisation techniques and machine
      learning to improve their value for applications in precision animal nutrition.
      The present paper reviews technologies that can monitor different nutritional
      processes relevant to animal production, profitability, environmental management
      and welfare. We discussed the model-data fusion approach in which data provided
      by sensor technologies can be used as input of nutrition simulation models in
      near-real time to produce more accurate, certain and timely predictions. We also
      discuss some examples that have taken this model-data fusion approach to
      complement the capabilities of both models and sensor data, and provided examples
      such as predicting feed intake and methane emissions. Challenges with
      automatising the nutritional management of individual animals include monitoring
      and predicting of the flow of nutrients including nutrient intake, quantity and
      composition of body growth and milk production, gestation, maintenance and
      physical activities at the individual animal level. We concluded that the
      livestock industries are already seeing benefits from the development of sensor
      and information technologies, and this benefit is expected to grow exponentially
      soon with the integration of nutrition simulation models and techniques for big
      data analysis. However, this approach may need re-evaluating or performing new
      empirical research in both fields of animal nutrition and simulation modelling to
      accommodate a new type of data provided by the sensor technologies.

PMID- 30277176
TI  - Retrospective evaluation of a clinical decision support tool for effective
      computed tomography angiography utilization in urgent brain imaging of suspected
      TIA/minor stroke in the emergency department.
AB  - CLINICIAN'S CAPSULE What is known about the topic? Canadian guidelines recommend
      that suspected transient ischemic attack (TIA) patients receive brain imaging in
      the emergency department; yet, high requisition rates for non-cerebrovascular
      patients exist. What did this study ask? What is the hypothetical impact that a
      clinical decision support tool (CDST) would have on computed tomography
      angiography (CTA) requisitions for suspected TIA patients. What did this study
      find? CDST use would have resulted in more TIA patients receiving CTA, while
      imaging fewer non-cerebrovascular patients. Why does this study matter to
      clinicians? A CDST could assist clinicians in applying the Canadian stroke
      guidelines as pragmatically as possible.

PMID- 30277177
TI  - Evaluation of emergency department ultrasound machines for the presence of occult
      blood.
AB  - CLINICIAN'S CAPSULE What is known about the topic? Bedside ultrasound is a
      frequently used tool in the emergency department (ED), with no standard cleaning
      protocols in place. What did this study ask? Is there visible and occult
      contamination of the ED ultrasound machine after daily use and in trauma? What
      did this study find? This study found that the ultrasound machine tested positive
      for occult blood contamination on 10% of daily tests and on 43% of assessments
      after use in trauma. Why does this study matter to clinicians? Standard cleaning
      practices should be implemented to reduce contamination rates.

PMID- 30277178
TI  - Goodpasture's Syndrome Following Alemtuzumab Therapy in Multiple Sclerosis.

PMID- 30277179
TI  - Comparison of Disaster Preparedness Between Urban and Rural Community Hospitals
      in New York State.
AB  - OBJECTIVE: The intent of this study was to determine whether there are
      differences in disaster preparedness between urban and rural community hospitals
      across New York State. METHODS: Descriptive and analytical cross-sectional survey
      study of 207 community hospitals; thirty-five questions evaluated 6 disaster
      preparedness elements: disaster plan development, on-site surge capacity,
      available materials and resources, disaster education and training, disaster
      preparedness funding levels, and perception of disaster preparedness. RESULTS:
      Completed surveys were received from 48 urban hospitals and 32 rural
      hospitals.There were differences in disaster preparedness between urban and rural
      hospitals with respect to disaster plan development, on-site surge capacity,
      available materials and resources, disaster education and training, and
      perception of disaster preparedness. No difference was identified between these
      hospitals with respect to disaster preparedness funding levels. CONCLUSIONS: The
      results of this study provide an assessment of the current state of disaster
      preparedness in urban and rural community hospitals in New York. Differences in
      preparedness between the two settings may reflect differing priorities with
      respect to perceived threats, as well as opportunities for improvement that may
      require additional advocacy and legislation. (Disaster Med Public Health
      Preparedness. 2018;page 1 of 5).

PMID- 30277180
TI  - Morphological study of apoptosis in granulosa cells and ovulation in a model of
      atresia in rat preovulatory follicles.
AB  - SummaryPrevious studies have established a model of atresia in preovulatory
      follicles after stimulation of immature rats with equine chorionic gonadotropin
      (eCG). This gonadotropin recruits a follicular pool and the deprivation of
      preovulatory luteinizing hormone (LH) surge induces the atresia in preovulatory
      follicles. The present study investigated the occurrence of ovulation and
      provided some morphological features of granulosa cell (GC) apoptosis of atretic
      follicles at 0, 48, 72 and 120 h after eCG stimulation. Histological sections of
      ovaries from untreated animals (0 h) showed primordial, primary, secondary and
      early antral follicles. After 48 h ovaries showed large antral follicles.
      Preovulatory follicles were observed at 72 h, and two out of five rats displayed
      cumulus-oocyte complexes (COCs) in the oviducts. All animals exhibited corpora
      lutea after 120 h. We observed increased estradiol (E2) levels 48 h after eCG
      treatment that might trigger an endogenous preovulatory gonadotropin surge.
      Higher progesterone (P4) level, which is the hallmark of a functional corpus
      luteum, was observed at 120 h. Atresia in secondary and antral follicles was
      observed by pyknotic granulosa cell nuclei in histology and positive
      immunolabelling for cleaved caspase 3. We also observed macrophages in secondary
      and antral follicles in atresia. Transmission electron microscopy revealed GCs
      with compacted chromatin against the nuclear envelope, nuclear fragmentation,
      cell shrinkage and fragmentation. No preovulatory follicles showed apoptosis of
      GCs. In conclusion, our results suggested the occurrence of an endogenous
      gonadotropin surge, promoting ovulation and preventing atresia of preovulatory
      follicles.

PMID- 30277181
TI  - Disparity Surface Reconstruction Based on a Stereo Light Microscope and Laser
      Fringes.
AB  - Microscopic vision systems based on a stereo light microscope (SLM) are used in
      microscopic measuring fields. Conventional measuring methods output the disparity
      surface based on stereo matching methods; however, these methods require that
      stereo images contain sufficient distinguishing features. Moreover, matching
      results typically contain many mismatched points. This paper presents a novel
      method for disparity surface reconstruction by combining an SLM and laser
      measuring techniques. The surfaces of small objects are scanned by a laser
      fringe, and a stereo image sequence containing laser stripes is obtained. The
      central contours of the laser stripes are extracted, and central contours are
      derived for alignment. A disparity coordinate system is then defined and used to
      analyze the relationship between the motion direction and reference plane. Next,
      the method of aligning disparity contours is proposed. The results show that our
      method can achieve a precision of +/-0.5 pixels and that the real and measured
      shapes described by the disparity surface are consistent based on our method. Our
      method is confirmed to perform much better than the conventional block-matching
      method. The disparity surface output obtained by our method can be used to
      measure the surface profiles of microscopic objects accurately.

PMID- 30277182
TI  - Impact of the Aliso Canyon Gas Leak on Respiratory-Related Conditions Among US
      Department of Veterans Affairs (VA) Users.
AB  - BACKGROUND: The largest gas leak in United States history occurred October 2015
      through February 2016 near Porter Ranch (PR), California, and prompted the
      temporary relocation of nearby residents because of health concerns related to
      natural gas exposure. METHODS: A retrospective cohort study was conducted using
      US Department of Veterans Affairs (VA) administrative and clinical data. On the
      basis of zip codes, we created two groups: PR (1920 patients) and San Fernando
      Valley (SFV) (15 260 patients) and examined the proportion of outpatient visits
      to VA providers with respiratory-related diagnoses between October 2014 and
      September 2017. RESULTS: We observed an increase in the proportion of visits in
      the PR group during the leak (7.0% vs 6.1%, P<0.005) and immediately after the
      leak (7.7% vs 5.3%, P<0.0001). For both groups, we observed a decrease in
      respiratory diagnoses one year after the leak (7.0% to 5.9%, P<0.05 PR; 6.1% to
      5.7%, P<0.01 SFV). CONCLUSION: Exposure to natural gas likely led to the observed
      increase in respiratory-related diagnoses during and after the PR gas leak. Early
      relocation following natural gas leaks may mitigate respiratory exacerbations.
      (Disaster Med Public Health Preparedness. 2018;page 1 of 5).

PMID- 30277183
TI  - Reassessment (after 15 Years) of Non-Patient Adults by the Rorschach Method.
AB  - The investigation of personality using the Rorschach Method has been historically
      established, however, its proper use requires continuous study, especially in
      regard to reliability, validity and normative references. This study's objective
      was to verify stability indicators of Rorschach (French Approach) through a
      reassessment (after 15 years) of non-patient adults previously addressed in the
      normative study by Pasian (1998). A total of 88 adults, aged between 34 and 69
      years old, of both sexes, with different socio-economic and educational levels,
      were reassessed in 2013 in the state of Sao Paulo, Brazil. The responses were
      independently rated by different judges, with adequate precision. The average
      results obtained collected in 1998 and 2013 were analyzed to determine if these
      two sets of data were significantly different from each other (Student's t test,
      p <= .05) and the following variables were compared: Productivity indices,
      Apprehension Modes/Location, Formal Quality, Determinants, Contents and Banality.
      The overall stability level in these variables is considerable (mean r = .28, +/-
      SD = 0.21). We discuss the theoretical approach of the Rorschach method regarding
      structural aspects of personality and developmental issues in personality
      assessment.

PMID- 30277184
TI  - Needs Assessment for a Targeted Health Promotion Campaign.
AB  - ABSTRACTSince the first human A/H7N9 infection in Hong Kong, there has been an
      ongoing threat of human-to-human transmission, potentially causing a pandemic.
      Because there is no vaccine for A/H7N9, the individual preventive measures become
      all the more important for reducing transmission. However, due to the ongoing
      threat of numerous avian influenza viruses, the public may suffer from pandemic
      media-fatigue. This study was done to assess the need for a targeted A/H7N9
      health promotion campaign. Steven and Gillam's framework using epidemiological,
      comparative, and corporate approaches was used to assess the need for a targeted
      A/H7N9 health promotion campaign.Local surveillance data showed that Hong Kong
      faces a double burden of increasing seasonal influenza activity and threat of an
      avian influenza pandemic. Experts warned of potential severity and difficulties
      in A/H7N9 control. In contrast, surveys showed that the Hong Kong public were
      suffering from pandemic-media-fatigue, lacked anxiety, had misconceptions, and
      were not vigilant in preventive practices. This was more evident in certain
      demographics. Content analysis showed that health promotion materials were not
      targeted or tailored in countries with human A/H7N9 cases. Targeted health
      promotion campaigns and framing the issue to increase public and media awareness
      are crucial in preventing the current pandemic-media-fatigue. (Disaster Med
      Public Health Preparedness. 2018;:page 1 of 9).

PMID- 30277185
TI  - Extent of implementation of food environment policies by the Malaysian
      Government: gaps and priority recommendations.
AB  - OBJECTIVE: To determine the degree of food environment policies that have been
      implemented and supported by the Malaysian Government, in comparison to
      international best practice, and to establish prioritised recommendations for the
      government based on the identified implementation gaps. DESIGN: The Healthy Food
      Environment Policy Index (Food-EPI) comprises forty-seven indicators of
      government policy practice. Local evidence of each indicator was compiled from
      government institutions and verified by related government stakeholders. The
      extent of implementation of the policies was rated by experts against
      international best practices. Rating results were used to identify and propose
      policy actions which were subsequently prioritised by the experts based on
      'importance' and 'achievability' criteria. The policy actions with relatively
      higher 'achievability' and 'importance' were set as priority recommendations for
      government action. SETTING: Malaysia. SUBJECTS: Twenty-six local experts.
      RESULTS: Majority (62 %) of indicators was rated 'low' implementation with no
      indicator rated as either 'high' or 'very little, if any' in terms of
      implementation. The top five recommendations were (i) restrict unhealthy food
      marketing in children's settings and (ii) on broadcast media; (iii) mandatory
      nutrition labelling for added sugars; (iv) designation of priority research areas
      related to obesity prevention and diet-related non-communicable diseases; and (v)
      introduce energy labelling on menu boards for fast-food outlets. CONCLUSIONS:
      This first policy study conducted in Malaysia identified a number of gaps in
      implementation of key policies to promote healthy food environments, compared
      with international best practices. Study findings could strengthen civil society
      advocacies for government accountability to create a healthier food environment.

PMID- 30277186
TI  - Cognitive test battery for evaluating elderly Chinese Americans.
AB  - : ABSTRACTObjectives:This study aimed to determine the diagnostic utility of a
      Chinese test battery for evaluating cognitive loss in elderly Chinese Americans.
      METHODS: Data from a pilot study at the Mount Sinai Alzheimer's Disease Research
      Center was examined. All participants were > 65 years old, primarily Chinese
      speaking, with adequate sensorimotor capacity to complete cognitive tests. A
      research diagnosis of normal mild cognitive impairment (MCI) or Alzheimer's
      disease (AD) was assigned to each participant in consensus conference. Composite
      scores were created to summarize test performance on overall cognition, memory,
      attention executive function, and language. Multivariable logistic regression
      models were used to assess the sensitivity of each cognitive domain for
      discriminating three diagnostic categories. Adjustment was made for demographic
      variables (i. e., age, gender, education, primary language, and years living in
      the USA). RESULTS: The sample included 67 normal, 37 MCI, and 12 AD participants.
      Performance in overall cognition, memory, and attention executive function was
      significantly worse in AD than in MCI, and performance in MCI was worse than in
      normal controls. Language performance followed a similar pattern, but differences
      did not achieve statistical significance among the three diagnostic groups.
      CONCLUSIONS: This study highlights the need for cognitive assessment in elderly
      Chinese immigrants.

PMID- 30277187
TI  - Making the invisible visible: Why does design matter for safe doffing of personal
      protection equipment?

PMID- 30277188
TI  - Subjective memory complaints predict baseline but not future cognitive function
      over three years: results from the Western Australia Memory Study.
AB  - : ABSTRACTBackground:This study investigated the characteristics of subjective
      memory complaints (SMCs) and their association with current and future cognitive
      functions. METHODS: A cohort of 209 community-dwelling individuals without
      dementia aged 47-90 years old was recruited for this 3-year study. Participants
      underwent neuropsychological and clinical assessments annually. Participants were
      divided into SMCs and non-memory complainers (NMCs) using a single question at
      baseline and a memory complaints questionnaire following baseline, to evaluate
      differential patterns of complaints. In addition, comprehensive assessment of
      memory complaints was undertaken to evaluate whether severity and consistency of
      complaints differentially predicted cognitive function. RESULTS: SMC and NMC
      individuals were significantly different on various features of SMCs. Greater
      overall severity (but not consistency) of complaints was significantly associated
      with current and future cognitive functioning. CONCLUSIONS: SMC individuals
      present distinctive features of memory complaints as compared to NMCs. Further,
      the severity of complaints was a significant predictor of future cognition.
      However, SMC did not significantly predict change over time in this sample. These
      findings warrant further research into the specific features of SMCs that may
      portend subsequent neuropathological and cognitive changes when screening
      individuals at increased future risk of dementia.

PMID- 30277189
TI  - Dairy cow nutrition in organic farming systems. Comparison with the conventional
      system.
AB  - The energy supplied by the high-forage diets used in organic farming may be
      insufficient to meet the requirements of dairy cattle. However, few studies have
      considered this problem. The present study aimed to analyze the composition of
      the diets and the nutritional status (focusing on the energy-protein balance of
      the diets) of dairy cattle reared on organic farms in northern Spain, which are
      similar to other organic farming systems in temperate regions. Exhaustive
      information about diets was obtained from organic (ORG) and representative
      conventional grazing (GRZ) and conventional no-grazing (CNG) farms. Samples of
      feed from the respective farms were analyzed to determine the composition.
      Overall, the diets used on the ORG farms were very different from those used on
      the CNG farms, although the difference was not as evident for GRZ. The CNG farms
      were characterized by a higher total dry matter intake with a high proportion of
      concentrate feed, maize silage and forage silage. By contrast, on ORG and GRZ
      farms, the forage, pasture and fibre intake were the most important variables.
      The ration used on ORG farms contained a significantly higher percentage of ADF
      and lower organic matter (OM) content than the rations used in both of the
      conventional farming systems, indicating that the diets in the former were less
      digestible. Although the protein concentration in the diets used on the grazing
      farms (ORG and GRZ) was higher than those used on CNG farms, the protein intake
      was similar. The results indicated an imbalance between energy and protein due to
      the low level of energy provided by the ORG diets, suggesting that more microbial
      protein could be synthesized from the available rumen-degraded dietary nitrogen
      if rumen-fermentable OM was not limiting. The imbalance between energy and
      protein led to a reduced amount of total digestible protein reaching the
      intestine and a lower milk yield per kilogram of CP intake on the ORG farms. In
      order to improve the protein use efficiency and consequently to reduce the loss
      of nitrogen to the environment, organic farming should aim to increase the energy
      content of cattle diets by improving forage quality and formulating rations with
      more balanced combinations of forage and grain.

PMID- 30277190
TI  - Self-Perception of Theoretical Knowledge and Practical Skills by Primary Health
      Care Physicians in Life-Threatening Emergencies.
AB  - OBJECTIVES: The goal of this study was to find out the training received in
      Urgent and Emergency Medicine (UEM) by the Primary Health Care (PHC) physicians
      of Asturias (Spain), as well as their perception of their own theoretical
      knowledge and practical skills in a series of procedures employed in life
      threatening emergencies (LTEs), and also to analyze the differences according to
      the geographical area of their work. METHODS: This was a cross-sectional survey
      of PHC physicians using an ad hoc survey of a sample of 213 physicians in
      Asturias regarding their self-perception of theoretical knowledge and practical
      skills in techniques used in LTEs by areas of work (rural, suburban, and urban).
      The interview was conducted by mail from April through May 2017. The data
      processing has used absolute and relative frequencies, as well as central
      tendency parameters and dispersion parameters. The estimates for the entire
      population have been made using confidence intervals for the mean of 95%. In the
      comparison of parameters, the differences between parameters with a probability
      of error less than five percent (P<.05) have been considered significant. For the
      comparison of means between the different techniques in the different areas of
      work, ANOVA was used. RESULTS: With respect to the training of physicians, in
      general, for managing emergencies, both at the regional level and by areas of
      work (rural, suburban, and urban), none of the sets analyzed attained five
      points. By areas of work, it was the suburban region where there was a greater
      average general level of knowledge. There were significant differences in the
      average theoretical knowledge and the average practical skills in the procedures
      studied according to the different areas of work. The greater number of
      significant differences was between the urban and suburban regions and within the
      urban area. CONCLUSIONS: It's necessary to ensure an adequate homogeneity of the
      levels of theoretical knowledge and practical skills of PHC physicians in order
      to guarantee the equity of provision of health care in emergencies in different
      geographical areas. Cernuda MartinezJA, Castro DelgadoR, Ferrero FernandezE,
      Arcos GonzalezP. Self-perception of theoretical knowledges and practical skills
      by primary health care physicians in life-threatening emergencies. Prehosp
      Disaster Med. 2018;33(5):508-518.

PMID- 30277191
TI  - Is Self-Compassion a Worthwhile Therapeutic Target for ICD-11 Complex PTSD
      (CPTSD)?
AB  - BACKGROUND: Two 'sibling' disorders have been proposed for the fourthcoming 11th
      version of the International Classification of Diseases (ICD-11): post-traumatic
      stress disorder (PTSD) and complex PTSD (CPTSD). Examining psychological factors
      that may be associated with CPTSD, such as self-compassion, is an important first
      step in its treatment that can inform consideration of which problems are most
      salient and what interventions are most relevant. AIMS: We set out to investigate
      the association between self-compassion and the two factors of CPTSD: the PTSD
      factor (re-experiencing, avoidance, sense of threat) and the Disturbances in Self
      Organization (DSO) factor (affect dysregulation, negative self-concept and
      disturbances in relationships). We hypothesized that self-compassion subscales
      would be negatively associated with both PTSD and DSO symptom clusters. METHOD: A
      predominantly female, clinical sample (n = 106) completed self-report scales to
      measure traumatic life events, ICD-11 CPTSD and self-compassion. RESULTS:
      Significant negative associations were found between the CPTSD DSO clusters of
      symptoms and self-compassion subscales, but not for the PTSD ones. Specifically
      it was also found that self-judgement and common humanity significantly predicted
      hypoactive affect dysregulation whereas self-judgement and isolation
      significantly predicted negative self-concept. CONCLUSIONS: Our results indicate
      that self-compassion may be a useful treatment target for ICD-11 CPTSD,
      particularly for symptoms of negative self-concept and affect dysregulation.
      Future research is required to investigate the efficacy and acceptability of
      interventions that have implicit foundations on compassion.

PMID- 30277192
TI  - Dietary supplementation of organic or inorganic chromium modulates the immune
      responses of broilers vaccinated with Avian Influenza virus vaccine.
AB  - Dietary supplementation with the organic chromium (Cr) has been shown to
      positively affect the immune function of poultry. However, to our knowledge, no
      experiment has been done to directly compare the impacts of Cr chloride and
      chromium picolinate (CrPic) on the immune responses of broilers vaccinated with
      Avian Influenza (AI) virus vaccine. Therefore, the present experiment was
      conducted to investigate the effects of supplemental Cr sources (Cr chloride and
      CrPic) and levels on the growth performance and immune responses of broilers
      vaccinated with AI virus vaccine so as to provide an effective nutritional
      strategy for improving immune function of broilers. A total of 432 1-day (d)-old
      male broiler chicks were used in a 1 plus 2*4 design. Chickens were given either
      a diet without Cr supplementation (control) or diets supplemented with 0.4, 0.8,
      1.6, or 3.2 mg Cr/kg as either Cr chloride or CrPic for 42 d. Compared to the
      control, dietary Cr supplementation had no effect (P>0.05) on average daily gain,
      average daily feed intake and gain : feed of broilers during the starter and
      grower phases, but increased (P<0.05) the relative weights of bursa of fabricius
      on d 21 and thymus, spleen, or bursa of fabricius on d 42, serum antibody titers
      against AI virus on d 21, 28, 35 and 42, blood T-lymphocyte transformation rate
      on d 28 and 42, blood T-lymphocyte percentage on d 42, and serum interleukin-2
      contents on d 28. Broilers fed the diets supplemented with the inorganic Cr
      chloride had higher (P<0.05) weights of thymus, spleen and bursa of fabricius
      than those fed the diets supplemented with the CrPic on d 42. In addition,
      broilers fed the diets supplemented with the CrPic had higher (P<0.05) antibody
      titers against AI virus than those fed the diets supplemented with the inorganic
      Cr chloride on d 21 and 35. These results indicate that dietary Cr
      supplementation improved immune responses of broilers vaccinated with AI virus,
      and the inorganic Cr chloride was more effective than the CrPic in increasing the
      relative weights of lymphoid organs, however, the CrPic was more effective than
      the inorganic Cr chloride in enhancing the serum antibody titer against AI virus.

PMID- 30277193
TI  - Life review for Chinese older adults in nursing homes: cultural acceptance and
      its effects.
AB  - : ABSTRACTObjectives:To explore the acceptance and effects of life review on
      older adults. DESIGN: A mixed-method study design was utilized in this study.
      SETTING: Four nursing homes located in Fuzhou, China. PARTICIPANTS: Sixty-two
      older adults from four nursing homes were selected according to the criteria set
      for this study. METHOD: Sixty-two older adults were randomly assigned to either
      the life review group or the control group, and 55 of them completed the study.
      Twenty-four participants took part in qualitative interviews after the life
      review program concluded. The Geriatric Depression Scale-15, Rosenberg Self
      Esteem Scale, and Purpose in Life Test were adopted to measure depression, self
      esteem, and meaning in life, respectively. RESULTS: The findings indicated that
      life review can reduce depressive symptoms and may be effective at improving self
      esteem and meaning in life among Chinese elderly people. More importantly, it
      revealed that cultural factors such as values, beliefs, and attitudes could
      interfere with participation in a life review. CONCLUSIONS: A culturally
      sensitive life review program could be an alternative approach to psychotherapy
      for promoting mental health in older adults.

PMID- 30277194
TI  - Comparison of PECARN, CATCH, and CHALICE clinical decision rules for pediatric
      head injury in the emergency department.
AB  - : Clinical questionWhat is the diagnostic accuracy of the PECARN, CATCH, and
      CHALICE clinical decision rules for pediatric head injury, and are the clinical
      decision rules valid when applied to a novel data set?Article chosenBabl FE,
      Borland ML, Phillips N, et al. Accuracy of PECARN, CATCH, and CHALICE head injury
      decision rules in children: a prospective cohort study. Lancet (London, England)
      2017;389(10087):2393-402. OBJECTIVES: The primary objective of the study was to
      determine the diagnostic accuracy and provide external validation for the PECARN,
      CATCH, and CHALICE clinical decision rules in a clinically homogeneous cohort of
      children. The secondary objective of this study was to perform a direct
      comparison of the three decision rules by assessing for the presence of traumatic
      brain injury (TBI) on computed tomography (CT) or the requirement for
      neurointervention.

PMID- 30277195
TI  - Secondary Electron Energy Contrast of Localized Buried Charge in Metal-Insulator
      Silicon Structures.
AB  - This paper presents a new method for creating and monitoring controlled localized
      negatively charged regions inside insulators with a scanning electron microscope
      (SEM). A localized buried charged region is created and observed close to the
      point where a high voltage primary beam (10 kV) strikes a metal-insulator-silicon
      specimen. The amount of buried charge within the insulator at any given moment
      can be dynamically monitored by detecting the appearance of a second peak in the
      secondary electron (SE) energy spectrum. SE energy spectral signals were obtained
      through the use of a compact high signal-to-noise energy analyzer attachment that
      was fitted on to the SEM specimen stage. An electrostatic model, together with
      Monte Carlo simulations, is presented to explain how the SE charge contrast
      effect functions. This model is then experimentally confirmed by using the SE
      energy spectral signal induced by a gallium ion beam inside a dual focused ion
      beam-SEM instrument.

PMID- 30277196
TI  - Mortality at Music Festivals: An Update for 2016-2017 - Academic and Grey
      Literature for Case Finding.
AB  - In 2016, the authors published a paper on music festival fatalities between the
      years 1999 and 2014 (n=722). In this Special Report, they provide an update on
      fatalities reported at music festivals globally for the period 2016-2017 (n=201).
      Using a search strategy designed to capture grey literature and media reports of
      music festival fatalities, reports of the overall frequency and cause-of-death
      breakdown for publicly reported, festival-related deaths are recorded. This
      update shows an increase in the frequency of festival-related fatality reports
      during the new period, together with an increase in the number of deaths
      attributable to terror (n=60) and overdose/poisoning (n=41). Drawing conclusions
      about the cause of this increase is challenging given the growth in Internet use,
      online media reports, and number of music festivals occurring annually when
      compared with the previous reporting period. The authors re-emphasize the need
      for a uniform reporting standard and reliable epidemiological data for fatalities
      related to music festivals, mass gatherings, and special events. TurrisSA,
      JonesT, LundA. Mortality at music festivals: an update for 2016-2017 - academic
      and grey literature for case finding. Prehosp Disaster Med. 2018;33(5):553-557.

PMID- 30277197
TI  - Case Report: Use of Plasma Exchange Followed by Convalescent Plasma Therapy in a
      Critically Ill Patient with Severe Fever and Thrombocytopenia Syndrome-Associated
      Encephalopathy: Cytokine/Chemokine Concentrations, Viral Loads, and Antibody
      Responses.
AB  - We describe the case of a patient with severe fever with thrombocytopenia
      syndrome (SFTS) complicated by SFTS-associated encephalopathy who was
      successfully treated with 4-day plasma exchange followed by two-time convalescent
      plasma therapy. During plasma exchange, the plasma cytokines IFN-alpha and IP-10
      gradually decreased without change of plasma viral load. However, plasma viral
      load gradually decreased after convalescent plasma therapy. This case provides
      important insights for understanding the mechanisms of experimental therapy in
      severely affected SFTS patients.

PMID- 30277198
TI  - Do Incarcerated Populations Serve as a Reservoir for Tuberculosis in South
      Africa?
AB  - Tuberculosis (TB) prevalence among incarcerated populations is as much as 1,000
      times higher than in the general population. This study evaluates whether
      correctional facilities serve as a reservoir through which TB is transmitted to
      surrounding communities. Tuberculosis test data were extracted from the South
      African National Health Laboratory Service database for patients tested for TB
      between 2005 and 2011. We conducted graphical analysis to assess the relationship
      of TB rates between incarcerated and non-incarcerated populations over time. We
      performed generalized linear modeling with a log link function to assess TB risk
      in communities surrounding correctional facilities, net of confounders. We
      assessed linkages between incarcerated and non-incarcerated populations over time
      using Granger causality analysis. Tuberculosis prevalence among incarcerated
      populations was four times higher than in the general population. Tuberculosis
      incidence rates in incarcerated and non-incarcerated populations followed similar
      trends over time. The presence of a correctional facility in a municipality was
      associated with 34.9% more detected TB cases (confidence interval: 11.6-63.2; P <
      0.01), controlling for potential confounders. Detected TB in incarcerated
      populations did not have predictive power in explaining detected TB rates in the
      non-incarcerated population after controlling for serial correlation in the time
      series data. Despite high TB prevalence, trends in correctional facilities do not
      appear to be driving temporal trends in the general population. However,
      correctional facilities still act as a TB reservoir that raises the overall TB
      risk in the vicinity. Intensified TB control policies for correctional
      facilities, formerly incarcerated individuals, and surrounding communities will
      reduce TB prevalence overall.

PMID- 30277199
TI  - Case Report: Squamous Cell Carcinoma Referred for Mohs Surgery Found to be
      Cutaneous Leishmaniasis.
AB  - Chronic skin lesions constitute a clinical diagnostic challenge. We report the
      case of a patient whose facial lesion was histopathologically compatible with
      squamous cell carcinoma and hence programmed for Mohs surgery. However, review of
      the clinical and epidemiological history led to laboratory diagnosis of cutaneous
      leishmaniasis, treatment with miltefosine, and complete resolution of the lesion.

PMID- 30277200
TI  - The Impact of Acquired Immune Deficiency Syndrome Treatment on Tuberculosis
      Detection at the National Level in South Africa.
AB  - Human immunodeficiency virus/Tuberculosis (HIV/TB) coinfection is particularly
      prevalent in South Africa, where TB has been the leading cause of death for more
      than a decade. The 2004-2008 national rollout of antiretroviral therapy (ART)
      provides a unique opportunity to examine the population-level impact of ART on
      the TB epidemic. We performed longitudinal regression analysis to follow the
      evolution of TB outcomes before and after the introduction of ART using a large
      data set from the National Health Laboratory Service. This is the first study to
      produce estimates of the impact of the ART rollout by exploiting staggered timing
      and geographic variation in the rollout. After ART became available in a health
      facility, 3.7% (P < 0.0001) more patients were tested for TB and 3.2% (P <
      0.0001) more received repeat testing; however, there was a steep rise in testing
      before the introduction of ART. Although the number of TB-positive patients
      increased by 4.3% (P = 0.0002) in the first year post-ART, the TB rate among
      tested patients fell by 2% points (8%, P = 0.001) after 2 years. Sputum smear
      testing declined relative to more technologically advanced diagnostics post-ART.
      Antiretroviral therapy availability increased the attention to TB screening and
      drew new patients into the health-care system. Small increases in the numbers of
      repeat patients are indicative of retention in care. The decline in TB rates post
      ART suggests that the reduction in TB risk due to improved immune functioning and
      health-care contact likely outweighed the increased TB risk because of the longer
      lifespan of ART initiators.

PMID- 30277201
TI  - Case Report: Acute Transverse Myelitis after Zika Virus Infection.
AB  - We report here one case of Zika virus (ZIKV) infection associated with auto
      immunity directed against the central nervous system in a Brazilian woman who
      developed acute transverse myelitis 9 days after recovery from an acute episode
      of fever with generalized erythema. Imaging of the spinal cord showed an
      elongated area on the T1-T10 level with gadolinium uptake. The diagnostic of the
      ZIKV infection was confirmed by cerebrospinal fluid and serum analysis. This
      patient had serum positivity for autoantibodies against myelin oligodendrocyte
      glycoprotein (MOG), a specific antibody against the myelin sheath. We propose
      that a direct central nervous system infection by ZIKV could lead to a specific
      auto-immunity against MOG protein.

PMID- 30277202
TI  - Impact of a Nonfatal Dengue Episode on Disability-Adjusted Life Years: A
      Systematic Analysis.
AB  - As dengue causes about 4,000 symptomatic nonfatal episodes for every dengue death
      globally, quantitative disability assessments are critical to assess the burden
      of dengue and the cost-effectiveness of dengue control interventions. This
      systematic analysis of disability or quality of life lost from a symptomatic
      nonfatal dengue episode combined a systematic literature review, statistical
      modeling, and probabilistic sensitivity analyses. We conceptualized a dengue
      episode as having two phases: acute and persistent symptoms. Our estimates for
      the acute phase, consisting of onset and recovery periods and defined as the
      first 20 days (0.054 year), were based on literature review. We searched PubMed,
      POPLINE, EconLit, Google Scholar, scientific conferences, and other sources, for
      "dengue" plus "quality of life" or related terms. From 4,322 initial entries, six
      met our criteria (original studies with empirical data). The median disability
      adjusted life year (DALY) burden for the acute phase was 0.011 (95% certainty
      interval [CI]: 0.006-0.015) for ambulatory episodes, 0.015 (CI: 0.010-0.020) for
      hospitalized episodes, and 0.012 (CI: 0.006-0.019) overall. Using literature
      reviews about persistent dengue, we estimated that 34% of episodes experienced
      persistent symptoms with a median duration of symptoms of 0.087 (CI: 0.040-0.359)
      year, which resulted in median DALYs of 0.019 (CI: 0.008-0.082). Thus, the
      overall median DALY burden was 0.031 (CI: 0.017-0.092) for ambulatory episodes,
      0.035 (CI: 0.024-0.096) for hospitalized episodes, and 0.032 (CI: 0.018-0.093)
      overall. Our dengue-specific burden of a dengue episode was 2.1 times the 2013
      Global Burden of Disease estimate. These literature-based estimates provide an
      empirical summary for policy and cost-effectiveness analyses.

PMID- 30277203
TI  - Sensitivity of the Point-of-Care Circulating Cathodic Antigen Urine Cassette Test
      for Diagnosis of Schistosoma mansoni in Low-Endemicity Settings in Cote d'Ivoire.
AB  - The sensitivity of a point-of-care circulating cathodic antigen (POC-CCA) urine
      cassette test for diagnosis of Schistosoma mansoni in low-endemicity settings is
      poorly understood. We conducted a cross-sectional survey in 14 villages in
      western Cote d'Ivoire and diagnosed children aged 9-12 years for schistosomiasis.
      Two stool samples were subjected to triplicate Kato-Katz thick smears each for
      diagnosis of S. mansoni, whereas a single urine sample was examined by POC-CCA
      for S. mansoni, filtration for Schistosoma haematobium, and reagent strip for
      microhematuria. According to the Kato-Katz technique, we found 45 out of 681
      children positive for S. mansoni (6.6%) with a mean intensity among infected
      children of 72.2 eggs per gram of stool. Point-of-care circulating cathodic
      antigen revealed a prevalence of S. mansoni of 33.0% when trace results were
      considered positive and 12.4% when trace results were considered negative. Eggs
      of S. haematobium were found in eight participants (1.2%), whereas the prevalence
      of microhematuria was 13.5%. A single POC-CCA urine cassette test revealed a
      several-fold higher prevalence of S. mansoni than multiple Kato-Katz thick smears
      in this low-endemicity area. Our findings have important ramifications for
      choosing an appropriate diagnostic tool in low-endemic areas that might be
      targeted for elimination.

PMID- 30277204
TI  - Integrating Blood Collection within Household Surveys: Lessons Learned from
      Nesting a Measles and Rubella Serological Survey within a Post-Campaign Coverage
      Evaluation Survey in Southern Province, Zambia.
AB  - Age-specific population immunity to many vaccine-preventable diseases can be
      measured using serological surveys. However, stand-alone serological surveys are
      infrequently conducted in low- and middle-income countries because of costs,
      operational challenges, and potential high refusal rates for blood collection.
      Nesting a serosurvey within a household cluster survey may overcome some of these
      challenges. We share lessons learned from nesting a serosurvey within a measles
      and rubella vaccination post-campaign coverage evaluation survey (PCES). In 15 of
      the 26 PCES clusters in Southern Province, Zambia, we collected dried blood spots
      from 581 participants aged 9 months and older. Household participation rates for
      the main PCES were higher in the serosurvey clusters (86%) than PCES-only
      clusters (71%), suggesting that a serosurvey can be successfully integrated
      without adversely affecting PCES participation. Among households that
      participated in the PCES, 80% also participated in the serosurvey and 86% of
      individuals available in the household provided a blood sample for the
      serosurvey. Substantial planning and coordination, additional staff training, and
      community mobilization were critical to the success of the serosurvey. Most
      challenges stemmed from using different data collecting tools and teams for the
      serosurvey and PCES. A more efficient design would be to fully integrate the
      serosurvey by adding blood collection and additional questions to the PCES.

PMID- 30277205
TI  - Case Report: Space-Occupying Lesion in the Liver Related to Preprandial Hunger
      and Hepatic Visceral Larva Migrans.
AB  - Visceral larva migrans (VLM) is one of the clinical syndromes of human
      toxocariasis. We report a case of hepatic VLM presenting preprandial malaise and
      epigastric discomfort in a 58-year-old woman drinking raw roe deer blood. The
      imaging studies of the abdomen showed a 74-mm hepatic mass featuring hepatic VLM.
      Anti-Toxocara canis IgG was observed in enzyme-linked immunosorbent assay (ELISA)
      and western blot. Despite anthelmintic treatment, the patient complained of newly
      developed cough and skin rash with severe eosinophilia. Hepatic lesion increased
      in size. The patient underwent an open left lobectomy of the liver. After the
      surgery, the patient was free of symptoms such as preprandial malaise, epigastric
      discomfort, cough, and skin rash. Laboratory test showed a normal eosinophilic
      count at postoperative 1 month, 6 months, 1 year, and 4 years. The initial
      optical density value of 2.55 of anti-T. canis IgG in ELISA was found to be
      negative (0.684) at postoperative 21 months. Our case report highlights that a
      high degree of clinical suspicion for hepatic VLM should be considered in a
      patient with a history of ingestion of raw food in the past, presenting severe
      eosinophilia and a variety of symptoms which reflect high worm burdens. Symptom
      remission, eosinophilia remission, and complete radiological resolution of
      lesions can be complete with surgery.

PMID- 30277206
TI  - Absence of Plasmodium falciparum K13 Propeller Domain Polymorphisms among Field
      Isolates Collected from the Brazilian Amazon Basin between 1984 and 2011.
AB  - Artemisinin resistance, presently confined to Southeast Asia and associated with
      mutations in the Plasmodium falciparum K13 (PfK13) propeller domain, represents a
      serious threat to global malaria control. This study aimed to provide baseline
      information for future artemisinin resistance surveillance, by analyzing the
      PfK13 propeller domain in P. falciparum field isolates collected from the
      Brazilian Amazon Basin between 1984 and 2011. A total of 152 P. falciparum mono
      infections were assessed, of which 118 (78%) were collected before and 34 (22%)
      after the introduction of artemisinin-based combination therapy (ACT) in 2006. An
      849-base pair fragment encoding the PfK13 propeller was amplified by nested PCR
      and sequenced in both directions. The sequences were compared with the reference
      sequence of P. falciparum 3D7. All samples showed wild-type sequences, thus, no
      mutations were observed. The results are in agreement with other recent reports
      and do not provide evidence for presence of PfK13 propeller domain polymorphisms
      associated with artemisinin resistance among P. falciparum field isolates in the
      Brazilian Amazon Basin neither before nor after the implementation of ACT.

PMID- 30277207
TI  - Case Report: Strongyloides stercoralis Hyperinfection in a Patient with HTLV-1: A
      Case Report of an Infection with Filariform and Rhabditiform Larvae, Eggs, and
      Free-Living Adult Females.
AB  - Strongyloides stercoralis is the main etiological agent of human
      strongyloidiasis. Severe strongyloidiasis is commonly associated to alcoholism,
      corticostereoid use, and human T cell lymphotropic virus type 1 (HTLV-1)
      coinfection. Herein, we report a case of a 13-year-old boy coinfected with S.
      stercoralis and HTLV-1, excreting several parasitic forms in the stool. The
      parasitological examination of his feces showed a large amount of filariform
      (about 3,000 larvae per gram of feces) and rhabditiform larvae (about 2,000
      larvae per gram of feces). In addition, free-living adult females (about 50
      parasites per gram of feces) and eggs (about 60 eggs per gram of feces) were
      detected. The main laboratory findings pointed to high IgE levels (228 UI/mL) and
      eosinophila (11.6%). The patient was treated with three courses of ivermectin
      (200 ug/kg twice, 2 weeks apart), achieving the parasitological cure. An increase
      of about 19 times in IL-17 level was observed following the parasitological cure,
      in addition to a decrease in the white blood cell, eosinophil counts, and IgE
      levels. This is the first case report, to our knowledge, in which an S.
      stercoralis adult free-living female was described in human feces and where an
      increase in IL-17 levels after Strongyloides treatment in a HTLV-1 coinfected
      individual was observed. This finding raises the need for further studies about
      IL-17 immunomodulation in S. stercoralis and HTLV-1 coinfected patients.

PMID- 30277208
TI  - Evidence of Likely Autochthonous Transmission of Chagas Disease in Arizona.
AB  - A healthy 16-year-old girl born and raised in Tucson, AZ, had screening and
      confirmatory testing revealing Chagas disease; clinical evaluation established
      that she had the indeterminate form of chronic Chagas disease with evidence of
      likely autochthonous transmission. Trypanosoma cruzi DNA was detected by
      conventional PCR in Triatoma rubida captured at her home.

PMID- 30277209
TI  - Making wildlife welcome in urban areas.
AB  - Careful design of the green spaces in cities will benefit both wild animals and
      humans.

PMID- 30277211
TI  - Mammal communities are larger and more diverse in moderately developed areas.
AB  - Developed areas are thought to have low species diversity, low animal abundance,
      few native predators, and thus low resilience and ecological function. Working
      with citizen scientist volunteers to survey mammals at 1427 sites across two
      development gradients (wild-rural-exurban-suburban-urban) and four plot types
      (large forests, small forest fragments, open areas and residential yards) in the
      eastern US, we show that developed areas actually had significantly higher or
      statistically similar mammalian occupancy, relative abundance, richness and
      diversity compared to wild areas. However, although some animals can thrive in
      suburbia, conservation of wild areas and preservation of green space within
      cities are needed to protect sensitive species and to give all species the chance
      to adapt and persist in the Anthropocene.

PMID- 30277214
TI  - Bulgaria: Health System Review.
AB  - This analysis of the Bulgarian health system reviews developments in its
      organization and governance, health financing, health care provision, health
      reforms and health system performance. With the 2015 National Health Strategy
      2020 at its core, there have been ambitious reform plans to introduce more
      decentralization, strategic purchasing and integrated care into the Bulgarian
      social health insurance system. However, the main characteristics of the
      Bulgarian health system, including a high level of centralization and a single
      payer to administer social health insurance, remain intact and very few reforms
      have been implemented (for example, the introduction of health technology
      assessment). There are multiple reasons for this, of which political fragility
      and stakeholder resistance are among the most important. Overall, Bulgaria marked
      notable progress on some health indicators (for example, life expectancy and
      infant mortality) but generally progress lags behind EU averages. What is more,
      the system has not been effective in reducing amenable mortality, as reflected in
      the unsteady improvement patterns in mortality due to malignant neoplasms. This
      is despite an increase in total health expenditure as a percentage of gross
      domestic product to 8.2% in 2015. The overall high out-of-pocket spending (47.7%
      of total health spending in 2015) has been growing and is increasingly worrisome.
      It evidences the low degree of financial protection by the Bulgarian social
      health insurance system and exacerbates the already considerable inequities along
      socioeconomic and regional fault lines. For instance, there are regional
      imbalances of medical professionals, which are more concentrated in urban areas,
      and accessibility to physicians is further deteriorating, especially in rural
      areas. Current reforms have to tackle these challenges and build consensus among
      stakeholders of the health system to unlock the standstill.

PMID- 30277212
TI  - Cryo-EM structure of respiratory complex I at work.
AB  - Mitochondrial complex I has a key role in cellular energy metabolism, generating
      a major portion of the proton motive force that drives aerobic ATP synthesis. The
      hydrophilic arm of the L-shaped ~1 MDa membrane protein complex transfers
      electrons from NADH to ubiquinone, providing the energy to drive proton pumping
      at distant sites in the membrane arm. The critical steps of energy conversion are
      associated with the redox chemistry of ubiquinone. We report the cryo-EM
      structure of complete mitochondrial complex I from the aerobic yeast Yarrowia
      lipolytica both in the deactive form and after capturing the enzyme during steady
      state activity. The site of ubiquinone binding observed during turnover supports
      a two-state stabilization change mechanism for complex I.

PMID- 30277210
TI  - An essential Staphylococcus aureus cell division protein directly regulates FtsZ
      dynamics.
AB  - Binary fission has been well studied in rod-shaped bacteria, but the mechanisms
      underlying cell division in spherical bacteria are poorly understood. Rod-shaped
      bacteria harbor regulatory proteins that place and remodel the division machinery
      during cytokinesis. In the spherical human pathogen Staphylococcus aureus, we
      found that the essential protein GpsB localizes to mid-cell during cell division
      and co-constricts with the division machinery. Depletion of GpsB arrested cell
      division and led to cell lysis, whereas overproduction of GpsB inhibited cell
      division and led to the formation of enlarged cells. We report that S. aureus
      GpsB, unlike other Firmicutes GpsB orthologs, directly interacts with the core
      divisome component FtsZ. GpsB bundles and organizes FtsZ filaments and also
      stimulates the GTPase activity of FtsZ. We propose that GpsB orchestrates the
      initial stabilization of the Z-ring at the onset of cell division and
      participates in the subsequent remodeling of the divisome during cytokinesis.

PMID- 30277215
TI  - Austria: Health System Review.
AB  - This analysis of the Austrian health system reviews recent developments in
      organization and governance, health financing, health care provision, health
      reforms and health system performance. Two major reforms implemented in 2013 and
      2017 are among the main issues today. The central aim of the reforms that put in
      place a new governance system was to strengthen coordination and cooperation
      between different levels of government and self-governing bodies by promoting
      joint planning, decision-making and financing. Yet despite these efforts, the
      Austrian health system remains complex and fragmented in its organizational and
      financial structure. The Austrian population has a good level of health. Life
      expectancy at birth is above the EU average and low amenable mortality rates
      indicate that health care is more effective than in most EU countries. Yet, the
      number of people dying from cardiovascular diseases and cancer is high compared
      to the EU-28 average. Tobacco and alcohol represent the major health risk
      factors. Tobacco consumption has not declined over the last decade like in most
      other EU countries and lies well above the EU-28 average. In terms of
      performance, the Austrian health system provides good access to health care
      services. Austrias residents report the lowest levels of unmet needs for medical
      care across the EU. Virtually all the population is covered by social health
      insurances and enjoys a broad benefit basket. Yet, rising imbalances between the
      numbers of contracted and non-contracted physicians may contribute to social and
      regional inequalities in accessing care. The Austrian health system is relatively
      costly. It has a strong focus on inpatient care as characterized by high hospital
      utilization and imbalances in resource allocation between the hospital and
      ambulatory care sector. The ongoing reforms therefore aim to bring down publicly
      financed health expenditure growth with a global budget cap and reduce
      overutilization of hospital care. Efficiency of inpatient care has improved over
      the reform period but the fragmented financing between the inpatient and
      ambulatory sector remain a challenge. Current reforms to strengthen primary
      health care are an important step to further shift activities out of the large
      and costly hospital sector and improve skill mix within the health workforce.

PMID- 30277213
TI  - Redox-dependent rearrangements of the NiFeS cluster of carbon monoxide
      dehydrogenase.
AB  - The C-cluster of the enzyme carbon monoxide dehydrogenase (CODH) is a
      structurally distinctive Ni-Fe-S cluster employed to catalyze the reduction of
      CO2 to CO as part of the Wood-Ljungdahl carbon fixation pathway. Using X-ray
      crystallography, we have observed unprecedented conformational dynamics in the C
      cluster of the CODH from Desulfovibrio vulgaris, providing the first view of an
      oxidized state of the cluster. Combined with supporting spectroscopic data, our
      structures reveal that this novel, oxidized cluster arrangement plays a role in
      avoiding irreversible oxidative degradation at the C-cluster. Furthermore,
      mutagenesis of a conserved cysteine residue that binds the C-cluster in the
      oxidized state but not in the reduced state suggests that the oxidized
      conformation could be important for proper cluster assembly, in particular Ni
      incorporation. Together, these results lay a foundation for future investigations
      of C-cluster activation and assembly, and contribute to an emerging paradigm of
      metallocluster plasticity.

PMID- 30277216
TI  - Spain: Health System Review.
AB  - This analysis of the Spanish health system reviews recent developments in
      organization and governance, health financing, health care provision, health
      reforms and health system performance. Overall health status continues to improve
      in Spain, and life expectancy is the highest in the European Union. Inequalities
      in self-reported health have also declined in the last decade, although long
      standing disability and chronic conditions are increasing due to an ageing
      population. The macroeconomic context in the last decade in the country has been
      characterized by the global economic recession, which resulted in the
      implementation of health system-specific measures addressed to maintain the
      sustainability of the system. New legislation was issued to regulate coverage
      conditions, the benefits package and the participation of patients in the
      National Health System funding. Despite the budget constraints linked to the
      economic downturn, the health system remains almost universal, covering 99.1% of
      the population. Public expenditure in health prevails, with public sources
      accounting for over 71.1% of total health financing. General taxes are the main
      source of public funds, with regions (known as Autonomous Communities) managing
      most of those public health resources. Private spending, mainly related to out-of
      pocket payments, has increased over time, and it is now above the EU average.
      Health care provision continues to be characterized by the strength of primary
      care, which is the core element of the health system; however, the increasing
      financing gap as compared with secondary care may challenge primary care in the
      long-term. Public health efforts over the last decade have focused on increasing
      health system coordination and providing guidance on addressing chronic
      conditions and lifestyle factors such as obesity. The underlying principles and
      goals of the national health system continue to focus on universality, free
      access, equity and fairness of financing. The evolution of performance measures
      over the last decade shows the resilience of the health system in the aftermath
      of the economic crisis, although some structural reforms may be required to
      improve chronic care management and the reallocation of resources to high-value
      interventions.

PMID- 30277217
TI  - Estonia: Health System Review.
AB  - This analysis of the Estonian health system reviews recent developments in
      organization and governance, health financing, health care provision, health
      reforms and health system performance. In 2017, the Estonian government took the
      historic step of expanding the revenue base of the health system, which has been
      a longstanding challenge. However, in terms of percentage of GDP it remains a
      small increase and long-term financial sustainability could still pose a problem.
      That said, if these additional funds are invested wisely, they could play a
      positive role in further improving the health system. Indeed, although Estonia
      has made remarkable progress on many health indicators (e.g. the strongest gains
      in life expectancy of all EU countries, strongly falling amenable mortality
      rates), there are opportunities for improvements. They include overcoming the
      large health disparities between socioeconomic groups, improving population
      coverage, developing a comprehensive plan to tackle workforce shortages, better
      managing the growing number of people with (multiple) noncommunicable diseases
      and further reaping the benefits of the e-health system, especially for care
      integration and clinical decision-making. Also in terms of quality, large strides
      have been made but the picture is mixed. Avoidable hospital admissions are among
      the lowest in Europe for asthma and chronic obstructive pulmonary disease (COPD),
      about average for congestive heart failure and diabetes, but among the worst for
      hypertension. Moreover, the 30-day fatality rates for acute myocardial infarction
      and stroke are among the worst in the EU. These outcomes suggest substantial room
      to further improve service quality and care coordination. The new NHP, which is
      currently being revised will be play a crucial role in the success of future
      reform efforts.

PMID- 30277218
TI  - Laser-induced ultrafast transport and demagnetization at the earliest time: first
      principles and real-time investigation.
AB  - It is generally believed that there are at least two ways to use an ultrafast
      laser pulse to demagnetize a magnetic sample. One is to directly photo
      demagnetize the system through spin-orbit coupling (SOC), and the other is to
      utilize ultrafast hot electron transport without SOC. The challenge is that these
      two processes are entangled on the same time scale. While the experimental
      results have been inconclusive, theoretical investigations are even scarcer,
      beyond those earlier studies based on spin superdiffusion. For instance, we do
      not even know how fast electrons move under laser excitation and how far they
      move. Here we carry out a first-principles time-dependent calculation to
      investigate how fast electrons actually move under laser excitation and how large
      the electron transport affects demagnetization on the shortest time scale. To
      take into account the transport effect, we implement the intraband transition in
      our theory. In the bulk fcc Ni, we find the effect of the spin transport on the
      demagnetization is extremely small, no more than 1%. The collective electron
      velocity in Ni is 0.4 A fs-1, much smaller than the Fermi velocity, and the
      collective displacement is no more than 0.1 A. But this does not mean that
      electrons do not travel fast; instead we find that electron velocities at two
      opposite crystal momenta cancel each other. We follow the Gamma-X line and find a
      huge dispersion in the velocities in the crystal momentum space. In the Fe/W(1 1
      0) thin film, the overall demagnetization is larger than Ni, and the Fermi
      velocity is higher than Ni. However, the effect of the spin transport is still
      small in the Fe/W(1 1 0) thin film. Based on our numerical results and existing
      experimental findings, we propose a different mechanism that can explain two
      latest experimental results. Our finding sheds new light on the effect of
      ballistic transport on demagnetization.

PMID- 30277219
TI  - Neurophysiological predictors and spectro-spatial discriminative features for
      enhancing SMR-BCI.
AB  - : Neural engineering research is actively engaged in optimizing the robustness of
      sensorimotor rhythms (SMR)-brain-computer interface (BCI) to boost its potential
      real-world use. OBJECTIVE: This paper investigates two vital factors in efficient
      and robust SMR-BCI design-algorithms that address subject-variability of optimal
      features and neurophysiological factors that correlate with BCI performance.
      Existing SMR-BCI research using electroencephalogram (EEG) to classify bilateral
      motor imagery (MI) focus on identifying subject-specific frequency bands with
      most discriminative motor patterns localized to sensorimotor region. APPROACH: A
      novel strategy to further optimize BCI performance by taking into account the
      variability of discriminative spectral regions across various EEG channels is
      proposed in this paper. MAIN RESULTS: The proposed technique results in a
      significant ([Formula: see text]) increase in average ([Formula: see text])
      classification accuracy by [Formula: see text] accompanied by a considerable
      reduction in number of channels and bands. The session-to-session transfer
      variation in spectro-spatial patterns using proposed algorithm is investigated
      offline and classification performance of the optimized BCI model is successfully
      evaluated in an online SMR-BCI. Further, the effective prediction of SMR-BCI
      performance with physiological indicators derived from multi-channel resting
      state EEG is demonstrated. The results indicate that the resting state activation
      patterns such as entropy and gamma power from pre-motor (fronto-central) and
      posterior (parietal and centro-parietal) areas, and beta power from posterior
      (centro-parietal) areas estimate BCI performance with minimum error. These
      patterns, strongly related to BCI performance, may represent certain cognitive
      states during rest. SIGNIFICANCE: Findings reported in this paper imply the need
      for subject-specific modelling of BCI and the prediction of BCI performance using
      multi-channel rest-state parameters, to ensure enhanced BCI performance.

PMID- 30277220
TI  - Nanowire based bioprobes for electrical monitoring of electrogenic cells.
AB  - The continuous miniaturization of electronic components and the emergence of nano
      biotechnology has opened new perspectives to monitor electrical activities at the
      single cell level. Here, we describe the creation of very high surface-to-volume
      ratio passive devices (vertical nanowire probes) using large-scale fabrication
      process, allowing to follow the electrical activity of mammalian neurons. Based
      on conventional silicon processing, the silicon nanowires were silicided in
      platinum in order to improve their electrochemical performances and to guarantee
      their biocompatibility. Very high signal to noise ratio was achieved (up to 2000)
      when measuring spontaneous action potentials. Moreover, this bio-platform was
      used to record the impact of various bio-chemical and electrical stimulations on
      neuronal activity. To conclude, this study proposes a thorough comparison of the
      characteristics and performances of these new nanowire-based nanoprobes with the
      main alternative systems published up to now.

PMID- 30277221
TI  - Peripheral dose around a mobile linac for intraoperative radiotherapy: radiation
      protection aspects.
AB  - The aim of this work is to analyse the scattered radiation produced by the mobile
      accelerator Mobetron 1000. To do so, detailed Monte Carlo simulations using two
      different codes, Penelope2008 and Geant4, were performed. Measurements were also
      done. To quantify the attenuation due to the internal structures, present in the
      accelerator head, on the scattered radiation produced, some of the main
      structural shielding in the Mobetron 1000 has been incorporated into the geometry
      simulation. Results are compared with measurements. Some discrepancies between
      the calculated and measured dose values were found. These differences can be
      traced back to the importance of the radiation component due to low energy
      scattered electrons. This encouraged us to perform additional calculations to
      separate the role played by this component. Ambient dose equivalent, H*(10),
      outside of the operating room (OR) has been evaluated using Geant4. H*(10) has
      been measured inside and outside the OR, being its values compatible with those
      reported in the literature once the low energy electron component is removed.
      With respect to the role played by neutrons, estimations of neutron H*(10) using
      Geant4 together with H*(10) measurements has been performed for the case of the
      12 MeV electron beam. The values obtained agree with the experimental values
      existing in the literature, being much smaller than those registered in
      conventional accelerators. This study is a useful tool for the clinical user to
      investigate the radiation protection issues arising with the use of these
      accelerators in ORs without structural shielding. These results will also enable
      to better fix the maximum number of treatments that could be performed while
      insuring adequate radiological protection of workers and public in the hospital.

PMID- 30277222
TI  - [Cellular Model Based on Laser Microsurgery of Cell Spheroids to Study the Repair
      Process].
AB  - In this study, modern techniques of laser microsurgery of cell spheroids have
      been used to developa new simple, reproducible model for studying the mechanisms
      of repair and regeneration in vitro. Nanosecondlaser pulses were applied to
      perform a microdissection of the outer and the inner zones of the spheroidsfrom
      dermal fibroblasts. To achieve effective dissection and preservation of spheroid
      viability, the optimalparameters were chosen: 355 nm wavelength, 100 Hz
      frequency, 2 ns pulse duration, laser pulses in the rangeof 7-9 MU J. After
      microdissection, we observed injury of the spheroids : the edges of the wound
      surface openedand the angular opening reached a value of more than 180 degrees . 
      As early as during the first hour after spheroidmicrodissection with laser
      radiation, the surviving cells changed their shape: cells on the spheroid surface
      anddirectly in the damaged area became rounded. One day after microdissection,
      the structure of the spheroidsbegan to partially recover, the cells in the
      surface layers began to take the original flattened shape; debris ofdead damaged
      cells and their fragments was gradually cleared from the spheroid composition. In
      the proposedmodel, the first data on stimulation of structure recovery of injured
      spheroids from dermal fibroblasts with aP199 synthetic polypeptide, which is used
      in cosmetology for the initiation of antiaging and regenerativeeffects in the
      skin, were received. After microdissection, recovery of the spheroids structure
      with a few surfacelayers of flattened imbricated arranged cells and polygonal
      cells of the inner zone in the presence of P199 peptidewas faster than in the
      control group, and was completed within 7 days, presumably due to the
      remodelingof the survived cells.

PMID- 30277223
TI  - Automated Unsupervised Behavioral State Classification using Intracranial
      Electrophysiology.
AB  - OBJECTIVE: Automated behavioral state classification in intracranial EEG (iEEG)
      recordings may be beneficial for iEEG interpretation and quantifying sleep
      patterns to enable behavioral state dependent neuromodulation therapy in next
      generation implantable brain stimulation devices. Here, we introduce a fully
      automated unsupervised framework to differentiate between awake (AW), sleep (N2),
      and slow wave sleep (N3) using intracranial EEG (iEEG) only and validated with
      expert scored polysomnography. APPROACH: Data from eight patients undergoing
      evaluation for epilepsy surgery (age 40+/-11, 3 female) with intracranial depth
      electrodes for iEEG monitoring were included. Spectral power features (0.1 -
      235Hz) spanning several frequency bands from a single electrode were used to
      classify behavioral states of patients into AW, N2, and N3. RESULTS: Overall,
      classification accuracy of 94%, with 94% sensitivity and 93% specificity across
      eight subjects using multiple spectral power features from a single electrode was
      achieved. Classification performance of N3 sleep was significantly better (95%,
      sensitivity 95%, specificity 93%) than that of the N2 sleep phase (87%,
      sensitivity 78%, specificity 96%). SIGNIFICANCE: Automated, unsupervised, and
      robust classification of behavioral states based on iEEG data is possible, and it
      is feasible to incorporate these algorithms into future implantable devices with
      limited computational power, memory, and number of electrodes for brain
      monitoring and stimulation.

PMID- 30277224
TI  - Endotoxin Contributes to Artificial Loosening of Prostheses Induced by Titanium
      Particles.
AB  - BACKGROUND Aseptic loosening of orthopedic implants caused by wear particles is a
      major cause of joint replacement failure. However, the mechanism of aseptic
      loosening has not yet been defined. The present study explored whether endotoxin
      adherent on the titanium (Ti) particles contributes to aseptic loosening.
      MATERIAL AND METHODS Limulus amebocyte lysate detection was conducted to detect
      the levels of endotoxin adhered to the Ti particles. A mouse air pouches model
      was established and mice were divided into 4 groups and injected with phosphate
      buffered saline (PBS) or Ti particles suspensions (0.1, 1, 10 mg/mL), following
      detection of the number of macrophages and the level of endotoxin. Scanning
      electron microscopy (SEM) was used to characterize the microstructures of Ti
      particles adhered with endotoxin. RESULTS In vitro experiments showed that the
      level of endotoxin adhered to the Ti particles was significantly increased after
      adding LPS back to these "endotoxin-free" particles. In vivo experiments showed
      that Ti particles injection significantly increased the number of macrophages and
      the level of endotoxin. CONCLUSIONS In conclusion, these results suggest that
      adherent endotoxin may play an important role in aseptic loosening induced by Ti
      particles.

PMID- 30277225
TI  - [High-pressure injection of paint into the hand: a severe injury that should not
      be underestimated].
AB  - : High-pressure injection into the hand causes a small skin lesion but severe
      subcutaneous tissue damage, which can result in permanent functional loss or
      amputation. Urgent and appropriate treatment is decisive. We present the case of
      an industrial painter who injected oil-based paint with a high-pressure gun into
      his left index finger. He was admitted to Accidents and Emergencies, where
      tetanus prophylaxis and antibiotic therapy were adminis-tered. Then, within four
      hours of his arrival at the hospital, the patient was brought to the operating
      room for surgical debridement. A year after the injury the finger's active and
      passive range of motion was complete, although paling of the skin together with
      hypersensitivity and dysfunction occurred on exposure to cold. The severity of
      these lesions, even if their initial appearance is benign, must be recognized and
      an immediate surgical debridement of the entire ischemic tissue should be
      performed, because delay in treatment is associated with higher rates of
      complication. KEYWORDS: High-pressure injuries. Paint injection. Hand.
      MANAGEMENT: 

PMID- 30277226
TI  - [Prevalence and typology of patients susceptible of palliative care deceased at
      home].
AB  - BACKGROUND: Identification of patients susceptible to palliative care (SPC) in
      the community is essential for improving their clinical management. The objective
      is to explore the SPC population and their typology of illness, according to sex.
      METHODS: Cross-sectional study, performed on the population of Malaga who died at
      home during 2015. Association between type of patient (SCP or identified as
      palliative by inclusion in the integrated care process (ICP)). Age, sex and type
      of disease were analyzed with Chi square and t-Student's test. RESULTS: Of 950
      patients attended to after dying at home, 417 (43.9%) were SCP and, of them, 277
      (66,4%) were included in the ICP. Males were more frequent in both populations
      (55.6 and 59.9%, respectively, p=0,26), with mean ages 78.6 and 76.2,
      respectively (p=0.01). The most frequent diseases in SCP patients were: cancer
      (61.9%), dementia and Alzheimer (19.9%), chronic ob-structive pulmonary disease
      (COPD) (6.2%) and heart failure (4.1%). People with cancer were more frequently
      included in the ICP (86.8%), while those with dementia and Alzheimer, COPD and
      Parkinson were less frequently included (20.5, 38.4 and 0.4% respectively). By
      sex, men suffered more from cancer and women from dementia. Percentage of
      inclusion in ICP was similar for men and women, stratified by disease.
      CONCLUSIONS: Almost half of the people who died at home are SCP although only two
      out of three are identified as such. Cancer is the most frequent SCP disease and
      the easiest one to identify, largely affecting men. Three out of four people with
      dementia died without being identified as PC, and they are mainly women.

PMID- 30277227
TI  - [Patient satisfaction in the Spanish National Health System].
AB  - BACKGROUND: Determine which key indicators of the Spanish National Health Service
      (NHS) influence patient satisfaction with the Spanish NHS and physicians (family
      doctors and specialists). METHOD: The mean for each indicator for each autonomous
      community, published by the Ministry of Health, Social Services and Equality,
      corresponding to the years 2005 to 2014, was related to patient satisfaction by
      means of multiple linear regression. RESULTS: Patient satisfaction with the NHS
      was ascertained at 57.32%, with general practitioners at 54.45% and specialist
      doctors at 55.11%. In the three types of satisfaction, the number of specialist
      doctors, hospital admissions and in-hospital mortality had a positive and
      significant influence, while the number of surgical interventions had a negative
      influence. The greater use of computerized tomography equipment and the hospital
      infection rate had a negative effect on satisfaction with the NHS and with
      specialist physicians, while the percentage of outpatient surgery had a positive
      effect. The average hospital stay shows a negative relationship with satisfaction
      with family doctors and specialists. CONCLUSIONS: Health policies should consider
      an increase in the number of medical specialists, favour ambulatory surgery,
      facilitate hospital treatment, monitor the effectiveness of surgical
      interventions, control hospital infections and moderate the prescription of drugs
      through the use of alternatives in order to increase patient satisfaction.

PMID- 30277228
TI  - Subtle changes in network composition impact the biodistribution and tumor
      accumulation of nanogels.
AB  - We studied the effect of subtle changes in side-chain chemistry and labelling
      with near infrared fluorophores of nanogels (NGs) prepared from thiolated
      poly(glycidol) on in vivo biodistribution in mice bearing human breast tumor
      xenografts. The stability and amphiphilic character of the side chain as well as
      labelling clearly influenced tumor targeting and overall biodistribution.

PMID- 30277229
TI  - Conformation of bis-nitroxide polarizing agents by multi-frequency EPR
      spectroscopy.
AB  - The chemical structure of polarizing agents critically determines the efficiency
      of dynamic nuclear polarization (DNP). For cross-effect DNP, biradicals are the
      polarizing agents of choice and the interaction and relative orientation of the
      two unpaired electrons should be optimal. Both parameters are affected by the
      molecular structure of the biradical in the frozen glassy matrix that is
      typically used for DNP/MAS NMR and likely differs from the structure observed
      with X-ray crystallography. We have determined the conformations of six bis
      nitroxide polarizing agents, including the highly efficient AMUPol, in their DNP
      matrix with EPR spectroscopy at 9.7 GHz, 140 GHz, and 275 GHz. The multi
      frequency approach in combination with an advanced fitting routine allows us to
      reliably extract the interaction and relative orientation of the nitroxide
      moieties. We compare the structures of six bis-nitroxides to their DNP
      performance at 500 MHz/330 GHz.

PMID- 30277230
TI  - Transition between tangential and co-axial liquid crystalline honeycombs in the
      self-assembly of Y-shaped bolapolyphiles.
AB  - p-Terphenyl based Y-shaped bolapolyphiles self-assemble into liquid crystalline
      honeycombs with co-axial organization of the pi-conjugated rods around columns
      filled by alkyl sidechains. In this new hexagonal honeycomb with P6/mmm symmetry
      the orientation of the pi-conjugated rods is perpendicular to the tangential
      honeycombs formed at lower temperature or with longer chain length.

PMID- 30277231
TI  - Rapid determination of binding parameters of chitin binding domains using chitin
      coated quartz crystal microbalance sensor chips.
AB  - Chitin present in fungal cell walls has been considered as a diagnostic polymer
      for the detection of fungal infections. Chitin staining can be achieved with
      different dyes such as Calcofluor white or Congo red, but these methods have not
      entered into clinical routine diagnosis due to problems with sensitivity and
      specificity. More accurate detection can be achieved using chitin binding domains
      (CBDs) from a large variety of naturally occurring proteins that specifically
      interact with chitin. The chitin binding properties of most of these proteins
      have not yet been determined, because chitin is an insoluble fibrillar material
      rendering accurate determination of chitin binding kinetics challenging. Here we
      report a quartz crystal microbalance with dissipation monitoring (QCM-D) based
      method to determine binding constants of CBDs on chitin-coated gold surfaces. For
      this purpose, chitin was trimethylsilylated and coated onto the sensor chips.
      After desilylation, regular fibril-like structures with a typical center-to
      center spacing of 85 nm were observed by atomic force microscopy. Using different
      experimental conditions and data evaluation methods for QCM-D measurements, we
      determined kon and koff and calculated the KD values for binding of a recombinant
      CBD from Bacillus circulans chitinase A1. Depending on the evaluation method, the
      KD values ranged between 0.6 and 2.5 MUM. The obtained KD values were in good
      agreement with those measured for other bacterial CBDs usually ranging between 1
      to 10 MUM. Hence, we propose that the experimental approach developed in this
      study can be applied to determine yet unknown binding affinities of various CBDs
      from different origin.

PMID- 30277232
TI  - Optical transient absorption experiments reveal the failure of formal kinetics in
      diffusion assisted electron transfer reactions.
AB  - The ultimate goal of chemical kinetics is to understand why a given reaction is
      fast or not. To this end it is necessary to count on robust and experimentally
      well tested theories. One of the difficulties, long recognized in the study of
      bimolecular reactions, is the role of the molecular displacement, i.e. diffusion.
      Nonetheless the field is still lacking a compelling amount of case studies
      contrasting physical models to experiments. By performing transient absorption
      experiments on the photo-induced electron transfer reaction between perylene and
      N,N-dimethylaniline in liquid solutions over many orders of magnitude in time, we
      try to understand the factors determining the kinetics and yields of the full
      photocycle. We present a method to overcome potential pitfalls in the extraction
      of the relevant quantities, the transient populations, from the experimental data
      due to the changes in band shapes and positions. The results are compared to
      simulations of two different theories: a reaction-diffusion approach based on the
      encounter theories, and a formal kinetic scheme. We conclude that while the
      former explains the observed trends in the kinetics with quencher concentration
      and viscosity exceptionally well, the latter fails. Moreover the analysis of the
      data with the assistance of encounter theory unveils effects that otherwise would
      pass unnoticed. This approach and its results exemplify the path to follow in
      other condensed media whenever diffusion is involved.

PMID- 30277233
TI  - Scaffold mediated gene knockdown for neuronal differentiation of human neural
      progenitor cells.
AB  - The use of human induced pluripotent stem cell-derived neural progenitor cells
      (hiPSC-NPCs) is an attractive therapeutic option for damaged nerve tissues. To
      direct neuronal differentiation of stem cells, we have previously developed an
      electrospun polycaprolactone nanofiber scaffold that was functionalized with
      siRNA targeting Re-1 silencing transcription factor (REST), by mussel-inspired
      bioadhesive coating. However, the efficacy of nanofiber-mediated RNA interference
      on hiPSC-NPCs differentiation remains unknown. Furthermore, interaction between
      such cell-seeded scaffolds with injured tissues has not been tested. In this
      study, scaffolds were optimized for REST knockdown in hiPSC-NPCs to enhance
      neuronal differentiation. Specifically, the effects of two different mussel
      inspired bioadhesives and transfection reagents were analyzed. Scaffolds
      functionalized with RNAiMAX Lipofectamine-siREST complexes enhanced the
      differentiation of hiPSC-NPCs into TUJ1+ cells (60% as compared to 22% in
      controls with scrambled siNEG after 9 days) without inducing high cytotoxicity.
      When cell-seeded scaffolds were transplanted to transected spinal cord
      organotypic slices, similar efficiency in neuronal differentiation was observed.
      The scaffolds also supported the migration of cells and neurite outgrowth from
      the spinal cord slices. Taken together, the results suggest that this scaffold
      can be effective in enhancing hiPSC-NPC neuronal commitment by gene-silencing for
      the treatment of injured spinal cords.

PMID- 30277234
TI  - Site-specific one-pot triple click labeling for DNA and RNA.
AB  - We report site-specific triple click labeling for DNA and RNA in a one-pot setup
      by performing inverse electron demand Diels-Alder reaction and strain-promoted
      and copper catalyzed click reactions sequentially. Our methodology can be applied
      to long and short nucleic acids alike, and could have broader potential for
      labeling other (bio-)molecules.

PMID- 30277235
TI  - Super long-life potassium-ion batteries based on an antimony@carbon composite
      anode.
AB  - A highly stable Sb based anode material of well-confined Sb@graphene@carbon
      (Sb@G@C) was developed for high performance PIBs. The Sb@G@C electrode exhibits a
      reversible capacity of 474 mA h g-1 at 100 mA g-1 (second charge), an outstanding
      long cycle stability over 800 cycles with a capacity retention as high as 72.3%
      and an excellent rate performance.

PMID- 30277236
TI  - Monomeric thorium chalcogenolates with bipyridine and terpyridine ligands.
AB  - Thorium chalcogenolates Th(ER)4 react with 2,2'-bipyridine (bipy) to form
      complexes with the stoichiometry (bipy)2Th(ER)4 (E = S, Se; R = Ph, C6F5). All
      four compounds have been isolated and characterized by spectroscopic methods and
      low-temperature single crystal X-ray diffraction. Two of the products,
      (bipy)2Th(SC6F5)4 and (bipy)2Th(SeC6F5)4, crystallize with lattice solvent,
      (bipy)2Th(SPh)4 crystallizes with no lattice solvent, and the selenolate
      (bipy)2Th(SePh)4 crystallizes in two phases, with and without lattice solvent. In
      all four compounds the available volume for coordination bounded by the two bipy
      ligands is large enough to allow significant conformational flexibility of
      thiolate or selenolate ligands. 77Se NMR confirms that the structures of the
      selenolate products are the same in pyridine solution and in the solid state.
      Attempts to prepare analogous derivatives with 2,2',6',2''-terpyridine (terpy)
      were successful only in the isolation of (terpy)(py)Th(SPh)4, the first terpy
      compound of thorium. These materials are thermochromic, with color attributed to
      ligand-to-ligand charge transfer excitations.

PMID- 30277238
TI  - Theoretical studies on the mechanism of Pd2+-catalyzed regioselective C-H
      acylation of azoxybenzenes with alpha-oxocarboxylic acids.
AB  - The reaction mechanism of the Pd2+-catalyzed regioselective C(sp2)-H acylation of
      azoxybenzenes with alpha-oxocarboxylic acids has been studied by density
      functional theory (DFT) calculations. This reaction mechanism involves five major
      steps: C-H activation, deprotonation, decarboxylation, reductive elimination and
      oxidation. Our calculation results indicate that the N-coordinated pathway is
      better than the O-coordinated pathway, which can be interpreted by distortion
      interaction analysis of the C-H bond activation transition states. Furthermore,
      we also suggest that the C-H bond acylation of aryl 1 is more favorable than that
      of aryl 2, which can be attributed to the fact that five-membered ring transition
      states are more favorable than four-membered ring transition states and the ON
      group has positive charge.

PMID- 30277240
TI  - Colloidal porous gold nanoparticles.
AB  - Porous Au nanostructures have attracted much attention for their wide uses as
      catalysts, sensors, actuators and surface-enhanced Raman scattering (SERS)
      substrates. The synthesis of porous Au nanostructures has mainly relied on
      dealloying approaches, which generally involve high-temperature treatment to form
      alloys and subsequent harsh chemical etching. Herein we report on an ambient wet
      chemistry method for the synthesis of colloidal porous Au nanoparticles. The
      synthesis takes advantage of the growth of Au on PbS nanocrystals accompanied by
      the etching of PbS by the growth solution. The obtained porous Au nanoparticles
      display a SERS enhancement factor of (1.23 +/- 0.10) * 107 on the individual
      particles under off-resonance excitation and a catalytic activity that is several
      times those of previously reported porous Au particles and porous Au sheets. Our
      results will have high impact on many SERS-based analytical and biomedical
      applications and on the field of Au-based catalysis.

PMID- 30277243
TI  - Influence of polymeric electrets on the performance of derived hybrid perovskite
      based photo-memory devices.
AB  - Organic-inorganic hybrid perovskite has become one of the most important
      photoactive materials owing to its intense light-harvesting property as well as
      its facile solution processability. Besides its photovoltaic applications, a
      novel photo-programmed transistor memory was recently developed based on the
      device architecture of a floating-gate transistor memory using a
      polymer/perovskite blend as the gate dielectric with the non-volatile memory
      characteristics of decent light response, applicable On/Off current ratio, and
      long retention time. In this study, we further clarify the influence of polymer
      matrix selection on the photo-response and memory properties of derived hybrid
      perovskite-based photo-memory devices. Four different host polymers, polystyrene
      (PS), poly(4-vinylphenol) (PVPh), poly(methyl methacrylate) (PMMA), and
      poly(methacrylic acid) (PMAA), were systematically investigated for comparison
      herein. This revealed that dissimilar chemical interactions existed between the
      host polymers and perovskite, resulting in the distinct memory behavior of the
      derived photo-memory devices, attributable to the different morphologies of the
      hybrid dielectric layers and the different sizes of the distributed perovskite
      nanoparticles (NPs). The photo-response behavior and the resultant On/Off current
      ratio increased as the size of the embedded perovskite NPs decreased, due to the
      enhanced photo-induced charge transfer across the dielectric/pentacene interface,
      benefiting from the better confinement effect of perovskite NPs in the polymer
      matrix. These results demonstrate the influence of perovskite NP aggregation at
      the dielectric/pentacene interface on the resultant memory behavior of the newly
      developed photo-memory device.

PMID- 30277241
TI  - A two-dimensional fingerprint nanoprobe based on black phosphorus for bio-SERS
      analysis and chemo-photothermal therapy.
AB  - Flake-shaped nanohybrids based on black phosphorus (BP) have been developed as
      multifunctional theranostic nanoplatforms for drug delivery, phototherapy and
      bioimaging. In this work, we report a facile strategy for fabrication of black
      phosphorus-Au nanoparticle hybrids (BP-AuNPs), which reveal an extraordinary near
      infrared (NIR) photothermal transduction efficiency and drug delivery capacity.
      The applications of the nanocomposites as therapeutic agents for high-performance
      chemo-photothermal tumor therapy are accomplished in vitro and in vivo. BP-AuNPs
      also exhibit wonderful surface-enhanced Raman scattering (SERS) activity under
      NIR laser excitation with a low Raman background, allowing BP-AuNPs to be used as
      a promising two-dimensional (2D) fingerprint nanoprobe for bio-SERS analysis. The
      cellular component identification and label-free live-cell bioimaging based on
      this type of 2D SERS substrate are generally investigated, which open up
      promising new perspectives in nanomedicine, including diagnosis, imaging and
      therapy.

PMID- 30277244
TI  - A coupled effect of dehydration and electrostatic interactions on selective ion
      transport through charged nanochannels.
AB  - Selective ion transport is an essential feature of biological ion channels. Due
      to the subnanometer size and negatively charged surface of ion channels, the ion
      selectivity is affected by both dehydration effects and electrostatic
      interactions. Their coupled effect on selective ion transport, however, has been
      elusive. Here, using molecular dynamics simulations, we study ion (Li+ and Mg2+)
      transport through subnanometer carbon nanotubes (CNTs) with varying charge
      densities. Our results indicate that the dehydration effect governs the ionic
      transport at low surface charge densities, hence the nanochannel shows a
      selectivity for Li+ ions. In contrast, the nanochannel switches to a selectivity
      for Mg2+ ions as the electrostatic interaction between the cations and the
      negatively charged wall dominates the transport at high surface charge densities.

PMID- 30277245
TI  - Photochemical strategies for the green synthesis of ultrathin Au nanosheets using
      photoinduced free radical generation and their catalytic properties.
AB  - Two-dimensional gold nanosheets represent a class of materials with excellent
      chemical and structural properties, which are often prepared using a template or
      toxic CO in organic solvents. Here, we report methylene blue (MB) radicals as a
      reducing agent to grow freestanding hexagonal ultrathin Au nanosheets with well
      tuned thicknesses in water. This is the first time that carbon organic radicals
      have been used as a reducing agent in metal nanosheet synthesis. Notably, no
      template is used throughout the synthesis process, and the yield of Au nanosheets
      is very high. It is found that MB is decisive in the growth of Au nanosheets
      because no Au nanosheets are obtained in the absence of MB with the same reaction
      parameters. The resulting nanosheets exhibit excellent catalytic activity during
      H2O2 decomposition to generate nontoxic O2. Thus, folic acid-conjugated oxygen
      generating nanosheets could detect cancer cells in serum samples with high
      sensitivity through pressure signals. Furthermore, the nanosheets exhibit highly
      efficient activity and selectivity toward the hydrogenation of alpha,beta
      unsaturated aldehydes. We anticipate that using MB radicals for the high-yield
      synthesis of 2D materials in this unique system has demonstrated their
      effectiveness and provides a green alternative route for producing other 2D
      nanomaterials.

PMID- 30277246
TI  - Altered zinc balance in the Atp7b-/- mouse reveals a mechanism of copper toxicity
      in Wilson disease.
AB  - Wilson disease (WD) is an autosomal recessive disorder caused by mutation in the
      ATP7B gene that affects copper transport in the body. ATP7B mutation damages
      copper transporter function, ultimately resulting in excessive copper
      accumulation and subsequent toxicity in both the liver and brain. Mechanisms of
      copper toxicity, however, are not well defined. The Atp7b-/- mouse model is well
      characterized and presents a hepatic phenotype consistent with WD. In this study,
      we found that the untreated Atp7b-/- mice accumulate approximately 2-fold excess
      hepatic zinc compared to the wild type. We used targeted transcriptomics and
      proteomics to analyze the molecular events associated with zinc and copper
      accumulation in the Atp7b-/- mouse liver. Altered gene expression of Zip5 and
      ZnT1 zinc transporters indicated a transcriptional homeostatic response, while
      increased copper/zinc ratios associated with high levels of metallothioneins 1
      and 2, indicated altered Zn availability in cells. These data suggest that copper
      toxicity in Wilson disease includes effects on zinc-dependent proteins.
      Transcriptional network analysis of RNA-seq data reveals an interconnected
      network of transcriptional activators with over-representation of zinc-dependent
      and zinc-responsive transcription factors. In the context of previous research,
      these observations support the hypothesis that mechanisms of copper toxicity
      include disruption of intracellular zinc distribution in liver cells. The
      translational significance of this work lies in oral zinc supplementation in
      treatment for WD, which is thought to mediate protective effects through the
      induction of metallothionein synthesis in the intestine. This work indicates
      broader impacts of altered zinc-copper balance in WD, including global
      transcriptional responses and altered zinc balance in the liver.

PMID- 30277248
TI  - Single atom alloy catalyst for SO3 decomposition: enhancement of platinum
      catalyst's performance by Ag atom embedding.
AB  - Recently, single atom alloy catalysts (SAA) have shown improved catalytic
      activity in numerous catalytic reactions. However, to date, single atom alloy
      (SAA) catalyst is not available for SO3 decomposition reaction, which is a key
      reactions in the hydrogen economy. Using state of the art density functional
      theory, we report a novel single Ag atom alloy Pt catalyst in the sub-nanometer
      length scale (AgPt9@Al2O3) showing superior catalytic behavior for SO3
      decomposition. It was found that alloying the alumina-supported platinum
      nanocluster with a single Ag atom lowers the activation barrier for S-O bond
      breaking by more than 50% in comparison with the pristine platinum counterpart.
      Activation barrier for AgPt9@Al2O3 catalyst is 0.52 eV, which is the lowest of
      any platinum based catalyst reported so far. At variance with pure Pt10@Al2O3,
      which tries to detach from the support during decomposition reaction, single atom
      alloy (SAA) nanocluster AgPt9@Al2O3 enhances binding with support, thus
      strengthening sintering resistance. Notably, influence of single Ag atom is also
      observed at larger length scale, i.e., at Pt(111) slab, where single Ag atom
      substituted surface Ag1Pt(111) shows ~30% reduction in activation barrier in
      contrast to a pristine surface. Single Ag atom works in bifunctional mode as it
      not only reduces the activation barrier, but also simultaneously weakly adsorbs
      the reaction product SO2, signifying relatively easier desorption and better
      recyclability. Deeper location of silver d-electrons and lesser electronegativity
      of silver is responsible for the better performance of single Ag atom alloyed Pt
      catalyst. We strongly believe that these remarkable results will open new avenues
      for future designing and fabrication of cost-effective catalysts for SO3
      decomposition.

PMID- 30277249
TI  - Molecules on rails: friction anisotropy and preferential sliding directions of
      organic nanocrystallites on two-dimensional materials.
AB  - Two-dimensional (2D) materials are envisaged as ultra-thin solid lubricants for
      nanomechanical systems. So far, their frictional properties at the nanoscale have
      been studied by standard friction force microscopy. However, lateral manipulation
      of nanoparticles is a more suitable method to study the dependence of friction on
      the crystallography of two contacting surfaces. Still, such experiments are
      lacking. In this study, we combine atomic force microscopy (AFM) based lateral
      manipulation and molecular dynamics simulations in order to investigate the
      movements of organic needle-like nanocrystallites grown by van der Waals epitaxy
      on graphene and hexagonal boron nitride. We observe that nanoneedle fragments -
      when pushed by an AFM tip - do not move along the original pushing directions.
      Instead, they slide on the 2D materials preferentially along the needles' growth
      directions, which act as invisible rails along commensurate directions. Further,
      when the nanocrystallites were rotated by applying a torque with the AFM tip
      across the preferential sliding directions, we find an increase of the torsional
      signal of the AFM cantilever. We demonstrate in conjunction with simulations that
      both, the significant friction anisotropy and preferential sliding directions are
      determined by the complex epitaxial relation and arise from the commensurate and
      incommensurate states between the organic nanocrystallites and the 2D materials.

PMID- 30277250
TI  - Evolution of 3D nanoporosity and morphology in selectively dealloying ternary
      Au55Cu25Si20 metallic glass ribbon with enhanced alcohol electro-oxidation
      performance.
AB  - Current fabrication methods of nanoporous gold (NPG) mainly rely on dealloying Ag
      Au binary crystalline precursors, typically Ag65Au35, with the "dealloying
      threshold" or "parting limit" above 55 at%. Here we report a simple chemical
      dealloying process, through selective dissolution of one element from a
      Au55Cu25Si20 metallic glass ribbon with low 'parting limit', and a novel peculiar
      three-dimensional 'cone shaped protrusion' nanoporous structure which has never
      been reported before. In this structure, a metastable gold silicide formed in the
      initial dealloying stage was decomposed into gold nanoparticles and amorphous
      SiOx in the later coarsening stage. Our finding provides insights into the
      underlying relationship between 'parting limit' and atomic level structure of
      metallic glass. Comprehensive discussions on the porosity evolution stages as
      well as the correlation between the porous 'cone shaped protrusion' development
      and potential energy landscape are made in this report. The fabricated 3D NPG
      also exhibited excellent electro-oxidation catalytic ability attributed to the
      high density of low-coordinated atomic sites provided by the gold particle inside
      of 'cone shaped protrusion'.

PMID- 30277251
TI  - High-performance transparent pressure sensors based on sea-urchin shaped metal
      nanoparticles and polyurethane microdome arrays for real-time monitoring.
AB  - An ultra-sensitive and transparent piezoresistive pressure sensor based on a sea
      urchin shaped metal nanoparticle (SSNP)-polyurethane (PU) composite with
      microdome arrays is successfully fabricated for the first time. The
      piezoresistive pressure sensor with microdome arrays was prepared using a
      nanoimprinting process based on an intermediate polymer substrate (IPS) replica
      mold. It showed a superior sensitivity (71.37 kPa-1) and a high optical
      transmittance (77.7% at 550 nm) due to the effective quantum tunneling effect
      even at small concentrations of conductive SSNP filler (6 mg mL-1). The high
      performance characteristics of the piezoresistive pressure sensor are attributed
      to the geometric effects of the microdome structure, especially the stress
      concentration at small contact spots and the deformation of the contact area. The
      piezoresistive pressure sensor with microdome arrays also exhibited a fast
      response/relaxation time (30 ms), ultra-low pressure detection (4 Pa), and
      excellent long-term stability under harsh conditions. In addition, the
      effectiveness of the piezoresistive pressure sensors in various sensing
      applications including sensing mapping, human arterial pulse monitoring, and the
      detection of muscle movement is also successfully demonstrated. It is anticipated
      that this novel transparent pressure sensor based on a SSNP-PU composite with
      microdome arrays will be a key component in the development of integrated
      transparent sensing applications.

PMID- 30277253
TI  - Fast naked-eye detection of zinc ions by molecular assembly-assisted
      polymerization of diacetylene.
AB  - Portable visual detection systems for environmental monitoring or diagnostic
      purposes are eagerly anticipated in low-resource settings. Inexpensive device
      requirements and visualization are key challenges for the development of any
      portable analysis system. We report herein a new strategy for developing portable
      rapid ion detection technology by the coupling of topochemical polymerization and
      supramolecular (SM) self-assembly. The rapid sol-gel or gel-sol phase transition
      of SM hydrogels has been widely applied for the detection of many important
      analytes including metal ions. However, one problem that remains is the
      difficulty inaccurately quantifying the degree of self-assembly with the naked
      eye. To address this problem, we designed a diacetylene-grafted peptide that can
      be polymerized following self-assembly into a hydrogel triggered by zinc ions.
      Before adding zinc ions, the molecules dissolved well in aqueous solution and
      arranged randomly, and were unable to be polymerized through UV light
      irradiation. After mixing with zinc ions, the peptide chelated with zinc ions
      immediately and self-assembled into a SM hydrogel. The molecules arranged orderly
      and could be easily polymerized through irradiation of a hand-held UV lamp in
      less than 2 minutes. The hydrogel showed a quick and sharp chromatic change from
      colorless to dark blue, which allowed the quantification of self-assembly (i.e.
      concentration of zinc ions) with the naked eye. In addition, the monomers were
      insensitive to light, pH and temperature changes, which is a highly desired
      characteristic in practical applications.

PMID- 30277254
TI  - Preparation of fluorinated PCL porous microspheres and a super-hydrophobic
      coating on fabrics via electrospraying.
AB  - In this study, fluorinated polycaprolactone (PCL) block polymers with different
      fluorine contents were synthesized via atom transfer radical polymerization
      (ATRP). An electrospraying technique was used to prepare fluorinated PCL
      microspheres with different microstructures. In contrast to the golf ball shape
      of unmodified PCL microspheres displaying porous pits on the surface, block
      polymer PCL-PTFOA(2 h) and PCL-PTFOA(6 h) microsphere surfaces displayed regular
      honeycomb-like pore structures. Thermally induced and evaporation-induced phase
      separations are proposed as the main mechanisms involved in the formation of the
      porous microstructures. The micro-phase separation between the two blocks of the
      fluorinated PCL copolymer is another factor that promoted the uniform collapse on
      the microsphere surface and the formation of its rugged wall. The surface
      roughness of the porous microspheres significantly improved their hydrophobicity,
      generating coating contact angles on aluminium foil substrates that measured as
      high as 162.4 +/- 1.5 degrees , which revealed that the surfaces were super
      hydrophobic. Lastly, cotton fabric was directly coated with the fluorinated
      polymer microspheres via electrospraying, resulting in super-hydrophobic surfaces
      and CAs reaching 160.0 +/- 1.3 degrees . The results demonstrate that
      electrospraying is a simple, innovative and cost-effective method for preparing
      polymer microspheres with controllable microstructures for fabric coating
      applications.

PMID- 30277255
TI  - Fabrication and understanding of Cu3Si-Si@carbon@graphene nanocomposites as high
      performance anodes for lithium-ion batteries.
AB  - Besides silicon's low electronic conductivity, another critical issue for using
      silicon as the anode for lithium-ion batteries (LIBs) is the dramatic volume
      variation (>300%) during lithiation/delithiation processes, which can lead to
      rapid capacity fading and poor rate capability, thereby hampering silicon's
      practical applications in batteries. To mitigate these issues, herein, we report
      our findings on the design and understanding of a self-supported Cu3Si
      Si@carbon@graphene (Cu3Si-SCG) nanocomposite anode. The nanocomposite is composed
      of Cu3Si-Si core and carbon shell with core/shell particles uniformly
      encapsulated by graphene nanosheets anchored directly on a Cu foil. In this
      design, the carbon shell, the highly elastic graphene nanosheet, and the formed
      conductive and inactive Cu3Si phase in Si serve as buffer media to suppress
      volume variation of Si during lithiation/delithiation processes and to facilitate
      the formation of a stable solid electrolyte interface (SEI) layer as well as to
      enable good transport kinetics. Chemomechanical simulation results quantitatively
      coincide with the in situ TEM observations of volume expansion and provide
      process details not seen in experiments. The optimized Cu3Si-SCG nanocomposite
      anode exhibits good rate performance and delivers reversible capacity of 483 mA h
      g-1 (based on the total weight of Cu3Si-SCG) after 500 cycles with capacity
      retention of about 80% at high current density of 4 A g-1, rendering the
      nanocomposite a desirable anode candidate for high-performance LIBs.

PMID- 30277256
TI  - Novel pi-extended hybrid xanthene dyes with two spirolactone rings for
      optoelectronic and biological applications.
AB  - The design, synthesis, and photophysical properties of organic fluorophores have
      attracted considerable research interest due to the utility of these compounds
      for various optoelectronic, analytical, and biological applications. In this
      study, we synthesized two novel pi-extended red-emitting hybrid xanthene dyes,
      each of which has two spirolactone rings and combines a seminaphthofluorescein
      moiety and a seminaphthorhodafluor moiety in a single molecule. The photophysical
      properties of the dyes in methanol in the presence of acid, base, and metal
      cations were investigated. Mono-ring-opened seminaphthofluorescein and
      seminaphthorhodafluor forms of the dyes could be obtained by the addition of OH-
      or H+, respectively. Owing to the changes in the absorbance spectra of the mono
      ring-opened forms induced by addition of H+ and OH-, the dyes could perform
      simultaneously the functions of an XOR gate and an INHIBIT gate, with the
      absorbances at 510 and 560 nm as outputs, respectively, and could act as half
      subtractors with H+ and OH- as inputs. Furthermore, stepwise ring-opening could
      be induced by Hg2+ ions in methanol. In water, the dyes existed in double-ring
      opened forms that emitted deep-red fluorescence and were mitochondria-targetable,
      suggesting that these chromophores might be useful as fluorescence tracers in
      biological applications. Because the absorption and fluorescence properties of
      these fluorophores can be regulated via their two spirolactone rings, we expect
      that these compounds will find utility in various optoelectronic, analytical, and
      biological applications.

PMID- 30277257
TI  - Skeletal malformations of Meox1-deficient zebrafish resemble human Klippel-Feil
      syndrome.
AB  - Klippel-Feil syndrome is a congenital vertebral anomaly, which is characterised
      by the fusion of at least two cervical vertebrae and a clinically broad set of
      symptoms, including congenital scoliosis and elevated scapula (Sprengel's
      deformity). Klippel-Feil syndrome is associated with mutations in MEOX1. The
      zebrafish mutant choker (cho) carries a mutation in its orthologue, meox1.
      Although zebrafish is being increasingly employed as fidelitous models of human
      spinal disease, the vertebral column of Meox1-deficient fish has not been
      assessed for defects. Here, we describe the skeletal defects of meox1cho mutant
      zebrafish utilising alizarin red to stain bones and chemical maceration of soft
      tissue to detect fusions in an unbiased manner. Obtained data reveal that
      meox1cho mutants feature aspects of a number of described symptoms of patients
      who suffer from Klippel-Feil syndrome and have mutations in MEOX1. These include
      vertebral fusion, congenital scoliosis and an asymmetry of the pectoral girdle,
      which resembles Sprengel's deformity. Thus, the meox1cho mutant zebrafish may
      serve as a useful tool to study the pathogenesis of the symptoms associated with
      Klippel-Feil syndrome.

PMID- 30277258
TI  - Low self-esteem, entrapment, and reason for living: A moderated mediation model
      of suicidal ideation.
AB  - Adolescent suicidal ideation has become a top public health concern. It is thus
      significant to explore both risk and protective factors of adolescent suicidal
      ideation. The present study tested a moderated mediation model of suicidal
      ideation in a sample of Chinese adolescents. Chinese adolescents of 1074 (54.2%
      females, aged between 11 and 18 years) completed questionnaires assessing self
      esteem, entrapment, reason for living, and suicidal ideation. We found that
      entrapment mediated the association between low self-esteem and suicidal
      ideation. The association between entrapment and suicidal ideation was moderated
      by reason for living. Findings of this study may expand our understanding of the
      development of suicidal ideation, and facilitate future research exploring the
      interplay of risk and protective factors of suicidality. Clinical implications of
      these findings were also discussed.

PMID- 30277259
TI  - Disparities in the management of paediatric splenic injury.
AB  - BACKGROUND: The non-operative management of splenic injury in children is
      recommended widely, and is possible in over 95 per cent of episodes. Practice
      appears to vary between centres. METHODS: The Trauma Audit and Research Network
      (TARN) database was interrogated to determine the management of isolated
      paediatric splenic injuries in hospitals in England and Wales. Rates of non
      operative management, duration of hospital stay, readmission and mortality were
      recorded. Management in paediatric surgical hospitals was compared with that in
      adult hospitals. RESULTS: Between January 2000 and December 2015 there were 574
      episodes. Children treated in a paediatric surgical hospital had a 95.7 per cent
      rate of non-operative management, compared with 75.5 per cent in an adult
      hospital (P < 0.001). Splenectomy was done in 2.3 per cent of children in
      hospitals with a paediatric surgeon and in 17.2 per cent of those treated in an
      adult hospital (P < 0.001). There was a significant difference in the rate of non
      operative management in children of all ages. There was some improvement in non
      operative management in adult hospitals in the later part of the study, but
      significant ongoing differences remained. CONCLUSION: The management of children
      with isolated splenic injury is different depending on where they are treated.
      The rate of non-operative management is lower in hospitals without a paediatric
      surgeon present.

PMID- 30277260
TI  - Enhanced contrast in X-ray microtomographic images of the membranous labyrinth
      using different X-ray sources and scanning modes.
AB  - The vestibular system, located in the inner ear, plays a crucial role in balance
      and gaze stabilisation by sensing head movements. The interconnected tubes with
      membranous walls of the vestibular system are located in the skull bone (the
      'membranous labyrinth'). Unfortunately, these membranes are very hard to
      visualise using three-dimensional (3D) X-ray imaging techniques. This difficulty
      arises due to the embedment of the membranes in the dense skull bone, the
      thinness of the membranes, and the small difference in X-ray absorption between
      the membranes and the surrounding fluid. In this study, we compared the
      visualisation of very small specimens (lizard heads with vestibular systems
      smaller than 3 mm) by X-ray computed micro-tomography (MUCT) based on synchrotron
      radiation and conventional sources. A visualisation protocol using conventional X
      ray MUCT would be very useful thanks to the ease of access and lower cost.
      Careful optimisation of the acquisition parameters enables detection of the
      membranes by using MUCT scanners based on conventional microfocus sources, but in
      some cases a low contrast-to-noise ratio (CNR) prevents fast and reliable
      segmentation of the membranes. Synchrotron radiation MUCT proved to be preferable
      for the visualisation of the small samples with very thin membranes, because of
      their high demands for spatial and contrast resolution. The best contrast was
      obtained by using synchrotron radiation MUCT working in phase-contrast mode,
      leading to up to twice as high CNRs than the best conventional MUCT results. The
      CNR of the synchrotron radiation MUCT scans was sufficiently high enough to
      enable the construction of a 3D model by the means of semi-automatic segmentation
      of the membranous labyrinth. Membrane thickness was found to range between 2.7
      and 36.3 MUm. Hence, the minimal membrane thickness was found to be much smaller
      than described previously in the literature (between 10 and 50 MUm).

PMID- 30277261
TI  - Malignant ovarian germ cell tumours in the post-menopausal population.
AB  - BACKGROUND: Malignant ovarian germ cell tumours (MOGCT) are uncommon in the
      general population and very rare in post-menopausal women. AIMS: To evaluate the
      demographics, treatment and survival of post-menopausal women with MOGCT treated
      at the Queensland Centre for Gynaecological Cancer (QCGC) and compare these with
      pre-menopausal women. MATERIALS AND METHODS: Retrospective analysis was performed
      of the QCGC database from January 1981 to February 2017. The disease course of
      post-menopausal women was compared with pre-menopausal women affected by MOGCT
      over the same period and compared with the world literature. RESULTS: There were
      six post-menopausal women with MOGCT treated at the QCGC compared with 166 pre
      menopausal women. In the post-menopausal group of women, there was no mortality
      directly attributed to germ cell ovarian disease compared with 10 (6.0%) women in
      the pre-menopausal group. CONCLUSIONS: Malignant ovarian germ cell tumours are a
      very rare condition in post-menopausal women. Despite some suggestion in the
      world literature that survival outcomes are worse in this population, this was
      not found in our study.

PMID- 30277262
TI  - Autism-linked CHD gene expression patterns during development predict multi-organ
      disease phenotypes.
AB  - Recent large-scale exome sequencing studies have identified mutations in several
      members of the CHD (Chromodomain Helicase DNA-binding protein) gene family in
      neurodevelopmental disorders. Mutations in the CHD2 gene have been linked to
      developmental delay, intellectual disability, autism and seizures, CHD8 mutations
      to autism and intellectual disability, whereas haploinsufficiency of CHD7 is
      associated with executive dysfunction and intellectual disability. In addition to
      these neurodevelopmental features, a wide range of other developmental defects
      are associated with mutants of these genes, especially with regards to CHD7
      haploinsufficiency, which is the primary cause of CHARGE syndrome. Whilst the
      developmental expression of CHD7 has been reported previously, limited
      information on the expression of CHD2 and CHD8 during development is available.
      Here, we compare the expression patterns of all three genes during mouse
      development directly. We find high, widespread expression of these genes at early
      stages of development that gradually becomes restricted during later
      developmental stages. Chd2 and Chd8 are widely expressed in the developing
      central nervous system (CNS) at all stages of development, with moderate
      expression remaining in the neocortex, hippocampus, olfactory bulb and cerebellum
      of the postnatal brain. Similarly, Chd7 expression is seen throughout the CNS
      during late embryogenesis and early postnatal development, with strong enrichment
      in the cerebellum, but displays low expression in the cortex and neurogenic
      niches in early life. In addition to expression in the brain, novel sites of Chd2
      and Chd8 expression are reported. These findings suggest additional roles for
      these genes in organogenesis and predict that mutation of these genes may
      predispose individuals to a range of other, non-neurological developmental
      defects.

PMID- 30277263
TI  - Magnetic resonance imaging findings in dogs with orbital inflammation.
AB  - OBJECTIVES: To describe MRI features of canine retrobulbar inflammation, their
      association with clinical findings and outcome and to assess the value of MRI in
      detecting orbital foreign bodies. MATERIALS AND METHODS: Clinical records of dogs
      with confirmed (23 of 31) and suspected (eight of 31) retrobulbar inflammation
      that underwent low field MRI studies were analysed retrospectively. RESULTS: Of
      the 31 dogs included in the study there was abscessation in 19. Extraocular
      myositis (27 of 31) was concurrent with strabismus in three cases. Of 25 patients
      with exophthalmos, 14 had concurrent optic nerve swelling and, of these, five had
      permanent loss of vision. There was no vision loss in patients without nerve
      swelling. One case of suspected retinal detachment on MRI was confirmed
      clinically. Extensive abnormal contrast enhancement in the temporalis, masseter
      and pterygoideus muscles was associated with facial (n=3) and trigeminal nerve
      deficits (n=1). Three patients with inflammation extending into the nasal cavity
      and frontal sinus (one of 31) or meningeal contrast enhancement (two of 31),
      showed optic and oculomotor nerve deficits. On MRI a foreign body was not visible
      in 20 of 31 case or "appeared likely" in 11 of 31 dogs. A foreign body was found
      at surgery in one case. CLINICAL SIGNIFICANCE: MRI outlines the extent of
      retrobulbar inflammation. Clinical findings were associated with imaging
      findings. MRI overestimated the presence of foreign bodies.

PMID- 30277264
TI  - Comparison of sampling methods for profiling cervicovaginal microbiome in rhesus
      macaques.
AB  - Cervicovaginal bacteria cause inflammation which in turn increases HIV risk.
      Profiling the cervicovaginal microbiome, therefore, is instrumental for vaccine
      development. We show that the microbiome profile captured by cervicovaginal
      lavage is comparable to samples obtained by vaginal swabs. Thus, lavage may serve
      as a sampling strategy in NHP vaccine studies.

PMID- 30277265
TI  - Magnetic resonance fingerprinting: a technical review.
AB  - Multiparametric quantitative imaging is gaining increasing interest due to its
      widespread advantages in clinical applications. Magnetic resonance fingerprinting
      is a recently introduced approach of fast multiparametric quantitative imaging.
      In this article, magnetic resonance fingerprinting acquisition, dictionary
      generation, reconstruction, and validation are reviewed.

PMID- 30277266
TI  - Chemical profiling by LC-MS/MS and HPLC fingerprint combined with chemometrics
      and simultaneous determination of 16 characteristic ingredients for the quality
      consistency evaluation of Shaoyao-Gancao Decoction.
AB  - In this paper, to evaluate the effect of the region of origin on the quality
      consistency of Shaoyao-Gancao Decoction (SGD), the SGD fingerprint was developed
      for the first time. Chemometric methods including similarity analysis,
      hierarchical clustering analysis and principal component analysis were employed
      to study the quality consistency of SGD. Meanwhile, high-performance liquid
      chromatography coupled with electrospray ionization quadrupole time-of-flight
      mass spectrometry was applied for comprehensive analysis of SGD and 93 compounds
      were tentatively characterized. Furthermore, a high-performance liquid
      chromatography method with multi-wavelength switching for simultaneous
      determination of 16 characteristic ingredients comprising gallic acid,
      oxypaeniflorin, albiflorin, paeoniflorin, liquiritin apioside, liquiritin,
      isoliquiritin apioside, galloylpaeoniflorin, 1,2,3,4,6-penta-O-galloyl-d
      galactopyranose (PGG), ononin, isoliquiritin, liquiritigenin,
      benzoylpaeoniflorin, glycyrrhizic acid, isoliquiritigenin and formononetin, was
      established. All 16 analytes show excellent linearity (R2  >= 0.9990) with
      recoveries ranging from 96.58 to 104.61% and limits of detection and
      quantification of 0.022-0.291 and 0.037-0.635 MUg/mL, respectively. Finally, it
      was successfully applied to determine 15 batches of SGD. The results of our
      research indicate that different regions of origin have a significant effect on
      the quality consistency of SGD, and its fingerprint combined with chemometrics
      and multi-ingredient determination comprise an efficient and reliable approach
      for quality consistency evaluation.

PMID- 30277267
TI  - Multiband RF pulse design for realistic gradient performance.
AB  - PURPOSE: Simultaneous multi-slice techniques are reliant on multiband RF pulses,
      for which conventional design strategies result in long pulse durations,
      lengthening echo-times so lowering SNR for spin-echo imaging, and lengthening
      repetition times for gradient echo sequences. Pulse durations can be reduced with
      advanced RF pulse design methods that use time-variable selection gradients.
      However, the ability of gradient systems to reproduce fast switching pulses is
      often limited and can lead to image artifacts when ignored. We propose a time
      efficient pulse design method that inherently produces gradient waveforms with
      lower temporal bandwidth. METHODS: Efficient multiband RF pulses with time
      variable gradients were designed using time-optimal VERSE. Using VERSE directly
      on multiband pulses leads to gradient waveforms with high temporal bandwidth,
      whereas VERSE applied first to singleband RF pulses and then modulated to make
      them multiband, significantly reduces this. The relative performance of these
      approaches was compared using simulation and experimental measurements. RESULTS:
      Applying VERSE before multiband modulation was successful at removing out-of-band
      slice distortion. This effectively removes the need for high frequency modulation
      in the gradient waveform while preserving the benefit of time-efficiency
      inherited from VERSE. CONCLUSION: We propose a time-efficient RF pulse design
      that produces gradient pulses with lower temporal bandwidth, reducing image
      artifacts associated with finite temporal bandwidth of gradient systems.

PMID- 30277268
TI  - A regional bolus tracking and real-time B1 calibration method for hyperpolarized
      13C MRI.
AB  - PURPOSE: Acquisition timing and B1 calibration are two key factors that affect
      the quality and accuracy of hyperpolarized 13C MRI. The goal of this project was
      to develop a new approach using regional bolus tracking to trigger Bloch-Siegert
      B1 mapping and real-time B1 calibration based on regional B1 measurements,
      followed by dynamic imaging of hyperpolarized 13C metabolites in vivo. METHODS:
      The proposed approach was implemented on a system which allows real-time data
      processing and real-time control on the sequence. Real-time center frequency
      calibration upon the bolus arrival was also added. The feasibility of applying
      the proposed framework for in vivo hyperpolarized 13C imaging was tested on
      healthy rats, tumor-bearing mice and a healthy volunteer on a clinical 3T scanner
      following hyperpolarized [1-13C]pyruvate injection. Multichannel receive coils
      were used in the human study. RESULTS: Automatic acquisition timing based on
      either regional bolus peak or bolus arrival was achieved with the proposed
      framework. Reduced blurring artifacts in real-time reconstructed images were
      observed with real-time center frequency calibration. Real-time computed B1
      scaling factors agreed with real-time acquired B1 maps. Flip angle correction
      using B1 maps results in a more consistent quantification of metabolic activity
      (i.e, pyruvate-to-lactate conversion, kPL). Experiment recordings are provided to
      demonstrate the real-time actions during the experiment. CONCLUSIONS: The
      proposed method was successfully demonstrated on animals and a human volunteer,
      and is anticipated to improve the efficient use of the hyperpolarized signal as
      well as the accuracy and robustness of hyperpolarized 13C imaging.

PMID- 30277269
TI  - Scan-specific robust artificial-neural-networks for k-space interpolation (RAKI)
      reconstruction: Database-free deep learning for fast imaging.
AB  - PURPOSE: To develop an improved k-space reconstruction method using scan-specific
      deep learning that is trained on autocalibration signal (ACS) data. THEORY:
      Robust artificial-neural-networks for k-space interpolation (RAKI) reconstruction
      trains convolutional neural networks on ACS data. This enables nonlinear
      estimation of missing k-space lines from acquired k-space data with improved
      noise resilience, as opposed to conventional linear k-space interpolation-based
      methods, such as GRAPPA, which are based on linear convolutional kernels.
      METHODS: The training algorithm is implemented using a mean square error loss
      function over the target points in the ACS region, using a gradient descent
      algorithm. The neural network contains 3 layers of convolutional operators, with
      2 of these including nonlinear activation functions. The noise performance and
      reconstruction quality of the RAKI method was compared with GRAPPA in phantom, as
      well as in neurological and cardiac in vivo data sets. RESULTS: Phantom imaging
      shows that the proposed RAKI method outperforms GRAPPA at high (>=4) acceleration
      rates, both visually and quantitatively. Quantitative cardiac imaging shows
      improved noise resilience at high acceleration rates (rate 4:23% and rate 5:48%)
      over GRAPPA. The same trend of improved noise resilience is also observed in high
      resolution brain imaging at high acceleration rates. CONCLUSION: The RAKI method
      offers a training database-free deep learning approach for MRI reconstruction,
      with the potential to improve many existing reconstruction approaches, and is
      compatible with conventional data acquisition protocols.

PMID- 30277271
TI  - Reduction of lipid contamination in MR spectroscopy imaging using signal space
      projection.
AB  - PURPOSE: Lipid contamination can complicate the metabolite quantification in MR
      spectroscopic imaging (MRSI). In addition to various experimental methods
      demonstrated to be feasible for lipid suppression, the postprocessing method is
      beneficial in the flexibility of applications. In this study, the signal space
      projection (SSP) algorithm is proposed to suppress the lipid signal in the MRSI.
      METHODS: The performance of lipid suppression using SSP and SSP combined with the
      Papoulis-Gerchberg (PG) algorithm (PG+SSP) is examined in 2D MRSI data and the
      results were compared with outer volume saturation (OVS) methods. Up to 10 lipid
      spatial components were extracted by SSP from lipid signals in the range of
      0.8~1.5 ppm. RESULTS: Our results show that most lipid signals were found in the
      first 4 to 5 components and that lipid signals on the spectra can be suppressed
      using 4 to 5 components. Metabolites concentrations were quantified using
      LCModel. Two regions of interest (ROIs) were manually selected on the peripheral
      and inner brain regions. The quantification of metabolites in terms of fitting
      reliability (CRLB) and spatial variations within ROIs (SpaVar) is improved using
      SSP. When 5 to 6 components were used in SSP and PG+SSP, the metabolite
      concentrations and the associated SpaVar and CRLB are at the same level as those
      from the OVS. CONCLUSION: We have demonstrated that the SSP method can be used to
      suppress the lipid signals of MRSI and SSP with 5 to 6 components is suggested to
      have a similar suppression performance as the OVS method.

PMID- 30277270
TI  - Machine learning improves classification of preclinical models of pancreatic
      cancer with chemical exchange saturation transfer MRI.
AB  - PURPOSE: We sought to assess whether machine learning-based classification
      approaches can improve the classification of pancreatic tumor models relative to
      more simplistic analysis methods, using T1 relaxation, CEST, and DCE MRI.
      METHODS: The T1 relaxation time constants, % CEST at five saturation frequencies,
      and vascular permeability constants from DCE MRI were measured from Hs 766 T, MIA
      PaCa-2, and SU.86.86 pancreatic tumor models. We used each of these measurements
      as predictors for machine learning classifier algorithms. We also used principal
      component analysis to reduce the dimensionality of entire CEST spectra and DCE
      signal evolutions, which were then analyzed using classification methods.
      RESULTS: The T1 relaxation time constants, % CEST amplitudes at specific
      saturation frequencies, and the relative Ktrans and kep values from DCE MRI could
      not classify all three tumor types. However, the area under the curve from DCE
      signal evolutions could classify each tumor type. Principal component analysis
      was used to analyze the entire CEST spectrum and DCE signal evolutions, which
      predicted the correct tumor model with 87.5% and 85.1% accuracy, respectively.
      CONCLUSIONS: Machine learning applied to the entire CEST spectrum improved the
      classification of the three tumor models, relative to classifications that used %
      CEST values at single saturation frequencies. A similar improvement was not
      attained with machine learning applied to T1 relaxation times or DCE signal
      evolutions, relative to more simplistic analysis methods.

PMID- 30277272
TI  - Functional tractography of white matter by high angular resolution functional
      correlation imaging (HARFI).
AB  - PURPOSE: Functional magnetic resonance imaging with BOLD contrast is widely used
      for detecting brain activity in the cortex. Recently, several studies have
      described anisotropic correlations of resting-state BOLD signals between voxels
      in white matter (WM). These local WM correlations have been modeled as functional
      correlation tensors, are largely consistent with underlying WM fiber orientations
      derived from diffusion MRI, and appear to change during functional activity.
      However, functional-correlation tensors have several limitations. The use of only
      nearest-neighbor voxels makes functional-correlation tensors sensitive to noise.
      Furthermore, adjacent voxels tend to have higher correlations than diagonal
      voxels, resulting in orientation-related biases. Finally, the tensor model
      restricts functional correlations to an ellipsoidal bipolar-symmetric shape, and
      precludes the ability to detect complex functional orientation distributions
      (FODs). METHODS: We introduce high-angular-resolution functional-correlation
      imaging (HARFI) to address these limitations. In the same way that high-angular
      resolution diffusion imaging (HARDI) techniques provide more information than
      diffusion tensors, we show that the HARFI model is capable of characterizing
      complex FODs expected to be present in WM. RESULTS: We demonstrate that the
      unique radial and angular sampling strategy eliminates orientation biases present
      in tensor models. We further show that HARFI FODs are able to reconstruct known
      WM pathways. Finally, we show that HARFI allows asymmetric "bending" and
      "fanning" distributions, and propose asymmetric and functional indices which may
      increase fiber tracking specificity, or highlight boundaries between functional
      regions. CONCLUSIONS: The results suggest the HARFI model could be a robust, new
      way to evaluate anisotropic BOLD signal changes in WM.

PMID- 30277273
TI  - Integrated radio-frequency/wireless coil design for simultaneous MR image
      acquisition and wireless communication.
AB  - PURPOSE: An innovative radio-frequency (RF) coil design that allows RF currents
      both at the Larmor frequency and in a wireless communication band to flow on the
      same coil is proposed to enable simultaneous MRI signal reception and wireless
      data transfer, thereby minimizing the number of wired connections in the scanner
      without requiring any modifications or additional hardware within the scanner
      bore. METHODS: As a first application, the proposed integrated RF/wireless coil
      design was further combined with an integrated RF/shim coil design to perform not
      only MR image acquisition and wireless data transfer, but also localized B0
      shimming with a single coil. Proof-of-concept phantom experiments were conducted
      with such a coil to demonstrate its ability to simultaneously perform these three
      functions, while maintaining the RF performance, wireless data integrity, and B0
      shimming performance. RESULTS: Performing wirelessly controlled shimming of
      localized B0 inhomogeneities with the coil substantially reduced the B0 root-mean
      square error (>70%) and geometric distortions in echo-planar images without
      degrading the image quality, signal-to-noise ratio (<1.7%), or wireless data
      throughput (maximum variance = 0.04 Mbps) of the coil. CONCLUSIONS: The
      RF/wireless coil design can provide a solution for wireless data transfer that
      can be easily integrated into existing MRI scanners for a variety of
      applications.

PMID- 30277274
TI  - 3D high-resolution imaging of 2-hydroxyglutarate in glioma patients using DRAG
      EPSI at 3T in vivo.
AB  - PURPOSE: To develop 3D high-resolution imaging of 2-hydroxyglutarate (2HG) at 3T
      in vivo. METHODS: Echo-planar spectroscopic imaging with dual-readout alternated
      gradients (DRAG-EPSI), which was recently reported for 2D imaging of 2HG at 7T,
      was tested for 3D imaging of 2HG at 3T. The frequency drifts and acoustic noise
      induced by DRAG-EPSI were investigated in comparison with conventional EPSI. Four
      patients with IDH-mutant gliomas were enrolled for 3D imaging of 2HG and other
      metabolites. A previously reported 2HG-tailored TE 97-ms PRESS sequence preceded
      the DRAG-EPSI readout gradients. Unsuppressed water, acquired with EPSI, was used
      as reference for multi-channel combination, eddy-current compensation, and
      metabolite quantification. Spectral fitting was conducted with the LCModel using
      in-house basis sets. RESULTS: With gradient strength of 4 mT/m and slew rate of
      20 mT/m/ms, DRAG-EPSI produced frequency drifts smaller by 5.5-fold and acoustic
      noise lower by 25 dB compared to conventional EPSI. In a 19-min scan, 3D DRAG
      EPSI provided images of 2HG with precision (CRLB <10%) at a resolution of 10 * 10
      * 10 mm3 for a field of view of 240 * 180 * 80 mm3. 2HG was estimated to be 5 mM
      in a pre-treatment patient. In 3 post-surgery patients, 2HG estimates were 3-6
      mM, and the 2HG distribution was different from the water-T2 image pattern or
      highly concentrated in the post-contrast enhancing region. CONCLUSION: Together
      with 2HG-optimized PRESS, DRAG-EPSI provides an effective tool for reliable 3D
      high-resolution imaging of 2HG at 3T in vivo.

PMID- 30277275
TI  - Transcutaneous oxygen measurement in humans using a paramagnetic skin adhesive
      film.
AB  - PURPOSE: Transcutaneous oxygen tension (TcpO2 ) provides information about blood
      perfusion in the tissue immediately below the skin. These data are valuable in
      assessing wound healing problems, diagnosing peripheral vascular/arterial
      insufficiency, and predicting disease progression or the response to therapy.
      Currently, TcpO2 is primarily measured using electrochemical skin sensors, which
      consume oxygen and are prone to calibration errors. The goal of the present study
      was to develop a reliable method for TcpO2 measurement in human subjects.
      METHODS: We have developed a novel TcpO2 oximetry method based on electron
      paramagnetic resonance (EPR) principles with an oxygen-sensing skin adhesive
      film, named the superficial perfusion oxygen tension (SPOT) chip. The SPOT chip
      is a 3-mm diameter, 60-MUm thick circular film composed of a stable paramagnetic
      oxygen sensor. The chip is covered with an oxygen-barrier material on one side
      and secured on the skin by a medical adhesive transfer tape to ensure that only
      the oxygen that diffuses through the skin surface is measured. The method
      quantifies TcpO2 through the linewidth of the EPR spectrum. RESULTS: Repeated
      measurements using a cohort of 10 healthy human subjects showed that the TcpO2
      measurements were robust, reliable, and reproducible. The TcpO2 values ranged
      from 7.8 +/- 0.8 to 22.0 +/- 1.0 mmHg in the volar forearm skin (N = 29) and 8.1
      +/- 0.3 to 23.4 +/- 1.3 mmHg in the foot (N = 86). CONCLUSIONS: The results
      demonstrated that the SPOT chip can measure TcpO2 reliably and repeatedly under
      ambient conditions. The SPOT chip method could potentially be used to monitor
      TcpO2 in the clinic.

PMID- 30277276
TI  - Caval to pulmonary 3D flow distribution in patients with Fontan circulation and
      impact of potential 4D flow MRI error sources.
AB  - PURPOSE: Uneven flow distribution in patients with Fontan circulation is
      suspected to lead to complications. 4D flow MRI offers evaluation using time
      resolved pathlines; however, the potential error is not well understood. The aim
      of this study was to systematically assess variability in flow distribution
      caused by well-known sources of error. METHODS: 4D flow MRI was acquired in 14
      patients with Fontan circulation. Flow distribution was quantified by the % of
      caval venous flow pathlines reaching the left and right pulmonary arteries.
      Impact of data acquisition and data processing uncertainties were investigated by
      (1) probabilistic 4D blood flow tracking at varying noise levels, (2) down
      sampling to mimic acquisition at different spatial resolutions, (3) pathline
      calculation with and without eddy current correction, and (4) varied segmentation
      of the Fontan geometry to mimic analysis errors. RESULTS: Averaged among the
      cohort, uncertainties accounted for flow distribution errors from noise <=3.2%,
      low spatial resolution <=2.3% to 3.8%, eddy currents <=6.4%, and inaccurate
      segmentation <=3.9% to 9.1% (dilation and erosion, respectively). In a worst-case
      scenario (maximum additive errors for all 4 sources), flow distribution errors
      were as high as 22.5%. CONCLUSION: Inaccuracies related to postprocessing
      (segmentation, eddy currents) resulted in the largest potential error (<=15.5%
      combined) whereas errors related to data acquisition (noise, low spatial
      resolution) had a lower impact (<=5.5%-7.0% combined). Whereas it is unlikely
      that these errors will be additive or affect the identification of severe
      asymmetry, these results illustrate the importance of eddy current correction and
      accurate segmentation to minimize Fontan flow distribution errors.

PMID- 30277277
TI  - Monitoring daily routine performance in quantitative NMR (qNMR) spectroscopy: Is
      the system suitability test necessary?
AB  - Nuclear magnetic resonance spectrometry (NMR) finds numerous applications in
      pharmacy, cosmetic, and food control as well as in developing tools for "big
      data" analysis. However, there remains a need for automated tools to assess
      instrument system suitability in real time for each particular routine sample. An
      automated procedure has been introduced to monitor a number of characteristics
      (resolution, symmetry, and half width) in real time after the measurement of two
      samples distributed by the vendor (0.3% CHCl3 in acetone-d6 with
      tetramethylsilane and 2 mM sucrose in H2 O-D2 O). The results over 11 months were
      discussed in terms of average values, standard deviations, and spectrometer
      variability. Moreover, multivariate statistical procedure was implemented to
      evaluate metrics generated from three NMR spectrometers. Performance of three NMR
      spectrometers (500 MHz with BBO Prodigy Cryoprobe, 500 MHz with BBFOPLUS
      SmartProbe, and 600 MHz with BBO Cryoprobe) differed significantly. The developed
      routine was also applied to calculate the performance characteristics during
      routine quantitative NMR experiments. The procedure was evaluated for NMR spectra
      of 659 active pharmaceutical ingredients dissolved in CDCl3 , DMSO, and CH3 OD.
      This test is more preferable than the routine procedure using standard solutions
      because the performance is estimated separately for each matrix at the specific
      time point of measurements. Our automated routine is the ideal tool for any NMR
      laboratory. In full automation, the NMR data are validated directly for each
      sample, making unnecessary daily measurements of standard solutions and manual
      evaluation to their NMR spectra.

PMID- 30277278
TI  - Temporal availability of public health care in developing countries of the
      Caribbean: An improved two-step floating catchment area method for estimating
      spatial accessibility to health care.
AB  - Due to restrictions on personnel availability, the service capacity at a health
      facility may vary day to day based on an established schedule. This temporal
      variability influences a user's choice set, modifying their possible choices. As
      a result, the spatial accessibility of public health care may be constantly
      reshaped rather than being a relatively static experience as commonly represented
      in place-based spatial accessibility literature. Building on the latest advances
      in the two-step floating catchment method, this study presents further
      advancements through the inclusion of health facility schedules to better
      represent health care availability in the assessment of accessibility. The
      results show that the proposed method reveals communities with relatively poor
      accessibility that are hidden with many existing methods. By exposing the
      available care within time windows, a more accurate picture of the services
      available to be accessed is revealed. The findings suggest that improvement in
      the number of doctor hours at health facilities may reduce the disparities found
      in accessibility scores for communities. Further, in public health care systems
      similarly structured, the spatial configuration of facilities with doctors can be
      considered at the administrative level to ensure adequate levels of access across
      the jurisdiction.

PMID- 30277279
TI  - How many beds? Capacity implications of hospital care demand projections in the
      Irish hospital system, 2015-2030.
AB  - Existing Irish hospital bed capacity is low by international standards while
      Ireland also reports the highest inpatient bed occupancy rate across OECD
      countries. Moreover, strong projected population growth and ageing is expected to
      increase demand for hospital care substantially by 2030. Reform proposals have
      suggested that increased investment and access to nonacute care may mitigate some
      increased demand for hospital care over the next number of years, and it is in
      this context that the Irish government has committed to increase the supply of
      public hospital beds by 2600 by 2027. Incorporating assumptions on the
      rebalancing of care to nonhospital settings, this paper analyses the capacity
      implications of projected demand for hospital care in Ireland to 2030. This
      analysis employs the HIPPOCRATES macrosimulation projection model of health care
      demand and expenditure developed in the ESRI to project public and private
      hospital bed capacity requirements in Ireland to 2030. We examine 6 alternative
      projection scenarios that vary assumptions related to population growth and
      ageing, healthy ageing, unmet demand, hospital occupancy, hospital length of
      stay, and avoidable hospitalisations. We project an increased need for between
      4000 and 6300 beds across public and private hospitals (an increase of between
      26.1% and 41.1%), of which 3200 to 5600 will be required in public hospitals.
      These findings suggest that government plans to increase public hospital capacity
      over the 10 years to 2027 by 2600 may not be sufficient to meet demand
      requirements to 2030, even when models of care changes are accounted for.

PMID- 30277281
TI  - A PTR virtual issue on the experimental and clinical pharmacology of the
      nutraceutical curcumin.

PMID- 30277280
TI  - A Biomimetic Supramolecular Approach for Charge Transfer between Donor and
      Acceptor Chromophores with Aggregation-Induced Emission.
AB  - Supramolecular assembly of chromophores with inherent resistance to aggregation
      induced self-quenching is significant to applications such as chemical sensing
      and organic light emitting diodes (OLEDs). In this work, molecular gels with
      aggregation-induced emission (AIE) are constructed by simply coassembling AIE
      chromophores (electron donor or acceptor) with a nonfluorescent molecular
      gelator. The binary gels are fluorescent even at very low concentrations of the
      AIE chromophores, indicating that the rotation of their aromatic cores is
      restricted in the gel network. In tertiary gels, the fluorescence of the donor
      chromophore can be efficiently reduced by the acceptor chromophore through a
      combination of static and dynamic quenching process, via charge transfer from the
      donor to the acceptor. This work demonstrates a convenient approach to fabricate
      a supramolecular charge transfer system using an AIE donor and acceptor.

PMID- 30277282
TI  - Guarana (Paullinia cupana Mart.) alters gut microbiota and modulates redox
      status, partially via caffeine in Wistar rats.
AB  - Microbiota alterations are observed in pathological conditions, and their
      regulation is a subject of great interest. Gut microbes are affected by diet, and
      plant polyphenols may have positive effect on gut microbiota; however, plant
      derived extracts may have toxic effects. Guarana (Paullinia cupana Mart.) is a
      nontraditional medicinal plant applied worldwide. Guarana yields an alkaloid and
      polyphenol-rich seed with antimicrobial, antioxidant, and anti-inflammatory
      properties, where caffeine is the major compound. We evaluated the effects of
      guarana seed powder (GSP) and purified caffeine on gut microbial composition and
      redox and inflammatory parameters in Wistar rats after 21 days of treatment.
      Fecal microbiota was analyzed utilizing 16S rDNA sequencing. Antioxidant enzymes
      activities from liver, kidney, and colon, as well as oxidative damage markers,
      were evaluated. Total nonenzymatic antioxidant potential was also evaluated.
      Microbiota was altered by both treatments, GSP and caffeine, without loss of
      diversity. In the liver, the kidney, and the colon, we observed a decrease in the
      antioxidant enzymes activities in the GSP group with no increase in the
      expression of oxidative damage markers, although some enzymes were also regulated
      by caffeine. Taken together, these results suggested that GSP ameliorates redox
      parameters but negatively affected gut microbiota, partially via caffeine.

PMID- 30277283
TI  - A Dynamically Stabilized Single-Nickel Electrocatalyst for Selective Reduction of
      Oxygen to Hydrogen Peroxide.
AB  - On-location electrochemical generation of H2 O2 is of great current interest.
      Herein, selective two-electron reduction of O2 to H2 O2 by a single [NiII (H2 O)6
      ]2+ cation that is dynamically associated with a negatively charged metal-organic
      layer (MOL) by hydrogen bonding and coulombic interactions is reported. In
      contrast, NiII centers covalently immobilized on the MOL reduce O2 to H2 O in a
      four- electron process. Oxygen adsorption by [NiII (H2 O)6 ]2+ followed by two
      electron reduction generates neutral [NiII (H2 O)4 (OH)(OOH)]0 , which
      momentarily disconnects from the negatively charged MOL to avoid the injection of
      additional electrons. Release of H2 O2 from [NiII (H2 O)4 (OH)(OOH)]0 regenerates
      [NiII (H2 O)6 ]2+ , which regains affinity to the MOL. Such dynamically
      associated NiII single-metal electrocatalysts ensure high selectivity and
      represent a new strategy for generating selective catalysts for electrochemical
      production of important chemicals.

PMID- 30277284
TI  - Ginsenoside Rg3 and Rh2 protect trimethyltin-induced neurotoxicity via prevention
      on neuronal apoptosis and neuroinflammation.
AB  - The acute exposure of trimethyltin (TMT) develops clinical syndrome characterized
      by amnesia, aggressive behavior, and complex seizures. This neurotoxicant
      selectively induces hippocampal neuronal injury and glial activation accompanied
      with resultant neuroinflammation. Here we report two candidates ginsenosides Rg3
      and Rh2 as neuroprotection agents using a mouse model of TMT intoxication via a
      single injection (2 mg/kg) and primary neuronal culture systems. Four-week
      administration of Rg3 or Rh2 significantly reduced TMT-induced seizures and
      behavioral changes. Rg3 and Rh2 significantly attenuated the oxidative stress
      evidenced by improvement on antioxidant enzymes and neuronal loss and astrocytic
      activation in mouse brain. In primary cultures, TMT induced significant neuronal
      death after 24-h intoxication and vigorous secretion of inflammatory cytokines
      (IL-1alpha/beta, IL-6, TNF-alpha, and MCP-1) in astrocytes. Pretreatment with Rg3
      or Rh2 not only reduced cell death but efficiently suppressed above mentioned
      inflammatory cytokines confirmed by antibody array test. The underlying
      protective mechanism by Rg3 and Rh2 was delineated through selective upregulation
      of PI3K/Akt and suppression of ERK activation. Intriguingly, Rg3 and Rh2
      protected oligodendrocyte progenitor cells (O-2A) from TMT intoxication via
      promoting type 2 astrocytic differentiation without further inflammatory
      activation. Collectively, Rg3 and Rh2 interventions aimed at reducing oxidative
      stress and neuroinflammation neurotoxicity therefore are of therapeutic benefit
      in TMT-induced neurodegeneration.

PMID- 30277285
TI  - A Versatile New Paradigm for the Design of Optical Nanosensors Based on Enzyme
      Mediated Detachment of Labeled Reporters: The Example of Urea Detection.
AB  - Here, a new bio-inspired nanoarchitectonics approach for the design of optical
      probes is presented. It is based on nanodevices that combine 1) an enzymatic
      receptor subunit, 2) a signaling subunit (consisting of a labeled reporter
      attached to a silica surface), and 3) a mechanism of communication between the
      two sites based on the production of chemical messengers by the enzymatic
      subunit, which induces the detachment of the reporter molecules from the silica
      surface. As a proof of concept, a urea nanosensor based on the release of Alexa
      Fluor-647-labeled oligonucleotide from enzyme-functionalized Janus gold
      mesoporous-silica nanoparticles (Au-MSNPs) was developed. The Janus particles
      were functionalized on the silica face with amino groups to which the labeled
      oligonucleotides were attached by electrostatic interactions, whereas the gold
      face was used for grafting urease enzymes. The nanodevice was able to release the
      fluorescent oligonucleotide through the enzyme-mediated hydrolysis of urea to
      ammonia and the subsequent deprotonation of amino groups on the silica face. This
      simple nanodevice was applied for the fluorometric detection of urea in real
      human blood samples and for the identification of adulterated milk. Given the
      large variety of enzymes and reporter species that could be combined, this is a
      general new paradigm that could be applied to the design of a number of optical
      probes for the detection of target analytes.

PMID- 30277286
TI  - Three-Stage Aromaticity Switching in Boron(III) and Phosphorus(V) N-Fused p
      Benziporphyrin.
AB  - Insertion of PCl3 or PhBCl2 into 5,10,15,20-tetraaryl-p-benziporphyrin prompted
      an intramolecular fusion affording anti-aromatic phosphorus(V) and non-aromatic
      boron(III) complexes of two N-fused dihydro-p-benziporphyrin isomers. These
      macrocycles are classified as carbatriphyrin due to the common [CNN]
      coordination. A sequence of direct transformations, triggered by protonation or
      two-electron redox processes, afforded a set of three mutually convertible N
      fused p-benziporphyrinoids, with distinct anti-aromatic, non-aromatic, and
      aromatic spectroscopic features.

PMID- 30277287
TI  - Histopathological impairment of common carp (Cyprinus carpio) induced through
      povidone-iodine exposure.
AB  - Histological biomarkers are one of the most advantageous tools in monitoring
      toxicological studies under experimental condition in laboratory. Since
      disinfectants are extensively inflowing into aquatic ecosystems, this study
      conducted on common carp to examine the effect of betadine solution on the liver
      and gill tissue. A 120-carp were kept for 2 weeks in the 100-l aquarium Different
      concentrations of povidone-iodine (betadine) prepared in three replications and a
      control group was prepared with no betadine (0, 5, 7, 8, and 9 ppm). Most lesions
      observed at gill tissue include adhesion secondary lamella, bleeding, destruction
      of secondary lamellae, hyperplasia secondary blades, curvature second blade,
      destroying the primary lamellae. Whats more, most lesions observed in liver
      tissue include bleeding, ascites liver, destruction of liver cells, bile
      stagnation. Betadine solution, could cause damage to the liver and gills tissues,
      although gill lesions were more evident than liver. Also increase of
      concentration led to elevation at lesions of both organs. Overally, the results
      revealed that using povidon-iodine as a disinfectant materials and entering into
      rivers and aquatic ecosystems could have undesirable effects and even death of
      this fish. Disinfectants, either in low or high concentration, could be very
      lethal for fish. However the defects seen in this study also could affect
      osmoregulation and metabolism as two main functions of gill and liver.

PMID- 30277288
TI  - Spatial configuration processing in visual word form perception and reading
      abilities in Chinese.
AB  - The analysis of spatial relations among components of a character is important in
      identifying visual word forms. We investigated such spatial configuration
      processing for Chinese characters in dyslexic children (aged 9-12 years) and two
      groups of typically developing children, matched according to chronological age
      or reading level. In this study, we used real characters and noncharacters to
      manipulate the spatial configuration between character components while
      preserving their local features. Both characters were displayed either in an
      upright or inverted position. Participants were asked to quickly determine
      whether the two presented stimuli were identical. A significant interaction
      between character type and character orientation showed children's matching
      performance was better in upright real characters than in the inverted version,
      but such effect was absent in noncharacters. This indicated that regardless of
      reading skills, children developed the ability to use local configuration
      information to visually identify words. Dyslexic children performed poorly in
      both real-character and noncharacter conditions. Furthermore, compared with
      control groups, dyslexic children performed worse in real-character conditions,
      which were close to the noncharacter performance of other groups. This reflected
      an impairment of global visual word-form processing (i.e., spatial configuration
      between components) in dyslexia.

PMID- 30277289
TI  - High recovery rate of consciousness by high-volume filtrate hemodiafiltration for
      fulminant hepatitis.
AB  - AIM: An artificial liver support (ALS) system sustaining patients with acute
      liver failure (ALF) in good condition until recovery of the native liver or
      performance of liver transplantation (LT), is essential for the improvement of
      the poor prognosis of ALF despite the lack of survival benefit. We aimed to
      investigate the efficacy of various ALS systems for fulminant hepatitis (FH)
      carried out in our liver unit so far, focusing on the restoration of
      consciousness from hepatic encephalopathy. METHODS: One hundred and ten
      consecutive adult Japanese patients with FH admitted to Chiba University Hospital
      (Chiba, Japan) between 1988 and 2016 who received ALS were analyzed. RESULTS:
      Recovery rate of consciousness improved with the increased dialysate flow rate
      and filtrate rate: 37.5% by plasma exchange (PE), 51.9% by PE + continuous
      hemodiafiltration (CHDF), 57.7% by slow PE (sPE) + high-flow CHDF (HFCHDF) (QD  =
      300 mL/min), 88.6% by HFCHDF (QD  = 500 mL/min) (+ sPE), and 92.9% by on-line HDF
      (OLHDF) (+ sPE). All patients except one, who could not be fully treated because
      of circulatory failure, recovered consciousness by OLHDF, including those whose
      liver function were completely abolished. Superiority of HFCHDF (QD  = 500
      mL/min) and OLHDF was also shown in patients who died without LT or received LT.
      CONCLUSIONS: More effective ALS should be recognized considering the extremely
      high recovery rate of consciousness. In particular, OLHDF with predilution
      reduces the cost of substitution fluid by supplying an unlimited amount of
      dialysate as substitution fluid prepared using an on-line system, and simplifies
      the procedure for the management.

PMID- 30277290
TI  - Adult-related haematopoietic stem cell donor experiences and the provision of
      information and psychosocial support: A systematic literature review.
AB  - For blood cancer patients, haematopoietic stem cells (HSC) donated by a relative
      can be lifesaving. However, related donors can face significant physical and
      psychosocial challenges. As the demand for adult-related HSC donors is
      increasing, it is important to review our understanding of adult-related HSC
      donors' need for and availability of information and psychosocial support with a
      view to identifying gaps in the literature. A systematic review of relevant
      studies (2000-2017) was conducted using five databases with supplementary hand
      searching. Sixteen studies involving 1,024 related HSC donors met the following
      criteria: English or Dutch language, peer-reviewed, sampled first-time-related
      HSC donors, >=18 years, haematological malignancies, assessed psychosocial
      aspects, retrospective or prospective and with or without comparison group. Data
      were abstracted, and study quality was assessed using the PRISMA criteria.
      Studies contained limited information on the provision of information and
      psychosocial support. Most studies addressed pre-donation information, and none
      reported providing information or support to donors post-donation. Additionally,
      few studies formally assessed unmet needs. Recommendations include improved
      transparency of reporting for the availability, sources and timing of information
      and psychosocial support, and the identification of unmet needs to enable the
      development of educational and psychosocial interventions for this invaluable
      donor population.

PMID- 30277291
TI  - Protocol identification and preservation of myxozoan parasites for microscopy
      with silver nitrate (Klein's dry) staining technique.
AB  - : The present study, discusses a first report of staining techniques with silver
      nitrate (AgNO3 ) stain for the preservation and identification of myxozoans
      globally. The silver nitrate stain was used to prepare permanent slide
      preparation of myxozoans with some adaptations made in our laboratory. Fresh air
      dried smear were stained with silver nitrate stain ensuing dark brown color polar
      capsules and light brown color of spore-wall. The stain is everlasting for years
      differing to other stains like Geimsa, iron-heamotoxylin Zeihl-Neelsen Blue, and
      trichome stains. RESEARCH HIGHLIGHTS: Stains usually fade with time and fail to
      disclose the morphological characters of the specimen. Present staining method
      helps to detect less infection in the tissue locating the myxospores. The Klein
      dry method (1958) is useful and suitable for long term preservation of the
      myxozoan slides and morphological description.

PMID- 30277292
TI  - Structural and Mechanistic Insight into Terpene Synthases that Catalyze the
      Irregular Non-Head-to-Tail Coupling of Prenyl Substrates.
AB  - Terpenoids have diverse structures and thus represent an important class of
      biologically active natural products. The structural diversity of terpenoids
      originates from the coupling of prenyl diphosphate substrates, such as
      isopentenyl diphosphate and dimethylallyl diphosphate. These isoprenyl
      diphosphates undergo canonical and sequential "head-to-tail" coupling catalyzed
      by terpene synthases, followed by modifications such as cyclization,
      hydroxylation, and glycosylation. In recent years, several terpene synthases that
      catalyze irregular "non-head-to-tail" couplings to afford branched terpenoids
      have been identified. This minireview describes structural and mechanistic
      insights into these unusual coupling reactions that provide a new strategy for
      the structural diversification of natural products.

PMID- 30277293
TI  - Lung cancer in Spanish women: The WORLD07 project.
AB  - The WORLD07 study was a female-specific database, to prospectively characterise
      the clinical, histological, molecular and treatment-related features in Spanish
      women with lung cancer. Data were collected from patients' medical records and
      patient interviews from October 2007 to December 2012. A total of 2,060 women
      were analysed: median age, 61.3 years; white, 98.6%; postmenopausal, 80.2%; and
      no smokers, 55% including never smokers and ex-smokers. A family history of
      cancer was found in 42.5% of patients, 12.0% of patients had had a previous
      history of cancer (breast cancer, 39.7%). Most patients (85.8%) were diagnosed of
      non-small-cell lung cancer (NSCLC), most commonly reported with adenocarcinoma
      (71.4%), which was stage IV at diagnosis in 57.6%. Median overall survival (OS)
      for the entire population was 24.0 months, with a 1- and 2-year survival rate of
      70.7% and 50.0% respectively. Median OS in patients with small-cell lung cancer
      was 18.8 months versus 25.0 months in patients with NSCLC (p = 0.011). Lung
      cancer appears to be a biologically different disease in women. By collecting
      prospective information about characteristics of women with lung cancer attending
      university hospitals in Spain, we hope to highlight the need to develop
      strategies based on gender differences and influence future healthcare policy.

PMID- 30277294
TI  - How I do a colonic J-pouch prolapse repair after coloanal anastomosis with an
      aponeurotic graft.

PMID- 30277295
TI  - No-touch ablation in hepatocellular carcinoma has the potential to prevent
      intrasubsegmental recurrence to the same degree as surgical resection.
AB  - AIM: The aim of this study was to clarify the utility of a no-touch pincer
      ablation procedure that uses bipolar electrodes to prevent intrasubsegmental
      tumor recurrence after radiofrequency ablation (RFA) for patients with
      hepatocellular carcinoma (HCC) compared to surgical resection. METHODS: We
      evaluated 175 consecutive patients with HCC (single nodule, tumor diameter <= 30
      mm) who underwent surgical resection (146 received partial resection) and 313
      patients who received RFA; 277 patients received touch ablation using a monopolar
      or bipolar RFA device, and 36 received no-touch ablation using a bipolar RFA
      device. Pretreatment arterial and portal phase dynamic computed tomography (CT)
      or magnetic resonance imaging (MRI) images were classified into four enhancement
      patterns: Type 1 and Type 2 are homogeneous enhancement patterns without or with
      increased arterial blood flow, respectively; Type 3 is a heterogeneous
      enhancement pattern with a septum-like structure; and Type 4 is an irregularly
      shaped ring structure enhancement pattern. RESULTS: Cumulative recurrence rates
      significantly differed between procedures (surgical resection, 7.5%; no-touch
      ablation, 2.9%; and touch ablation, 17.7% at the third year; P = 0.005).
      Multivariate Cox proportional hazards analysis revealed that enhancement pattern
      type (Type 3: hazard ratio [HR], 2.95; P = 0.002; and Type 4: HR, 3.88, P =
      0.002), treatment procedure (touch ablation: HR, 3.36; P < 0.001), and serum
      alpha-fetoprotein level (>=30 MUg/L: HR, 1.87; P = 0.009) were significant
      predictors of intrasubsegmental recurrence. No significant differences between no
      touch ablation and surgical resection were observed. CONCLUSION: The no-touch
      pincer ablation procedure has the potential to prevent intrasubsegmental
      recurrence after RFA for patients with HCC to the same degree as partial
      resection.

PMID- 30277296
TI  - Visible-Light-Induced Pyridylation of Remote C(sp3 )-H Bonds by Radical
      Translocation of N-Alkoxypyridinium Salts.
AB  - Metal-free, visible-light-induced site-selective heteroarylation of remote C(sp3
      )-H bonds has been accomplished through the design of N-alkoxyheteroarenium salts
      serving as both alkoxy radical precursors and heteroaryl sources. The transient
      alkoxy radical can be generated by the single-electron reduction of an N
      alkoxypyridinium substrate by a photoexcited quinolinone catalyst. Subsequent
      radical translocation of the alkoxy radical forms a nucleophilic alkyl radical
      intermediate, which undergoes addition to the substrate to achieve remote C(sp3 )
      H heteroarylation. This cascade strategy provides a powerful platform for remote
      C(sp3 )-H heteroarylation in a controllable and selective manner and is well
      suited for late-stage functionalization of complex bioactive molecules.

PMID- 30277297
TI  - Exploring comorbid depression and physical health trajectories: A case-based
      computational modelling approach.
AB  - While comorbid depression/physical health is a major clinical concern, the
      conventional methods of medicine make it difficult to model the complexities of
      this relationship. Such challenges include cataloguing multiple trends,
      developing multiple complex aetiological explanations, and modelling the
      collective large-scale dynamics of these trends. Using a case-based complexity
      approach, this study engaged in a richly described case study to demonstrate the
      utility of computational modelling for primary care research. N = 259 people were
      subsampled from the Diamond database, one of the largest primary care depression
      cohort studies worldwide. A global measure of depressive symptoms (PHQ-9) and
      physical health (PCS-12) were assessed at 3, 6, 9, and 12 months and then
      annually for a total of 7 years. Eleven trajectories and 2 large-scale collective
      dynamics were identified, revealing that while depression is comorbid with poor
      physical health, chronic illness is often low dynamic and not always linked to
      depression. Also, some of the cases in the unhealthy and oscillator trends remain
      ill without much chance of improvement. Finally, childhood abuse, partner
      violence, and negative life events are greater amongst unhealthy trends.
      Computational modelling offers a major advance for health researchers to account
      for the diversity of primary care patients and for developing better prognostic
      models for team-based interdisciplinary care.

PMID- 30277298
TI  - Unusual case of acute large bowel obstruction: endometriosis mimicking sigmoid
      malignancy.

PMID- 30277299
TI  - High single-cell diversity in carbon and nitrogen assimilations by a chain
      forming diatom across a century.
AB  - Almost a century ago Redfield discovered a relatively constant ratio between
      carbon, nitrogen and phosphorus in particulate organic matter and nitrogen and
      phosphorus of dissolved nutrients in seawater. Since then, the riverine export of
      nitrogen to the ocean has increased 20 fold. High abundance of resting stages in
      sediment layers dated more than a century back indicate that the common
      planktonic diatom Skeletonema marinoi has endured this eutrophication. We
      germinated unique genotypes from resting stages originating from isotope-dated
      sediment layers (15 and 80 years old) in a eutrophied fjord. Using secondary ion
      mass spectrometry (SIMS) combined with stable isotopic tracers, we show that the
      cell-specific carbon and nitrogen assimilation rates vary by an order of
      magnitude on a single-cell level but are significantly correlated during the
      exponential growth phase, resulting in constant assimilation quota in cells with
      identical genotypes. The assimilation quota varies largely between different
      clones independent of age. We hypothesize that the success of S. marinoi in
      coastal waters may be explained by its high diversity of nutrient demand not only
      at a clone-specific level but also at the single-cell level, whereby the
      population can sustain and adapt to dynamic nutrient conditions in the
      environment.

PMID- 30277300
TI  - Laparoscopic resection of an urachal abscess caused by migration of a fish bone:
      a case report.

PMID- 30277301
TI  - When does curatively treated colorectal cancer recur? An Australian perspective.
AB  - BACKGROUND: While most colorectal cancer (CRC) recurrences reportedly occur
      within 3 years following curative treatment, many studies are limited by short
      term follow-up. This study examines the time to recurrence of CRC in a large
      Australian cohort with a long follow-up period and assesses whether time to
      recurrence has changed over time. METHODS: A comprehensive prospective database
      of patients undergoing resection for CRC is maintained at Concord Hospital,
      Sydney. Demographic and time to recurrence data were extracted for patients who
      developed a recurrence following potentially curative resection for colon cancer
      from 1995 to 2010 and rectal cancer from 1971 to 2010. Non-deceased patients had
      a minimum of 5 years follow-up. RESULTS: Between 1995 and 2010, 2575 patients
      with CRC underwent surgery. After exclusions, 386 had recurrence following
      potentially curative resection, ranging from 1 to 172.5 months (median 20.3)
      after treatment. Within 1 year, 27.5% recurred, 57.5% by 2 years, 74.6% by 3
      years, 85.5% by 4 years and 89.6% by 5 years. There was no difference in time to
      recurrence between colon and rectal cancers (P = 0.674). Among patients having a
      potentially curative resection for rectal cancer between 1971 and 2010, 386
      recurred. There was no difference in time to recurrence by decade (P = 0.863).
      CONCLUSION: The majority of recurrences occurred within 3 years of curative
      treatment. Had surveillance been limited to 5 years, detection of more than 10%
      of recurrences would have been delayed. Time to recurrence for rectal cancer has
      not changed in over 40 years, despite treatment advances.

PMID- 30277302
TI  - Case report of hypereosinophilic syndrome presenting as severe ischaemic colitis.

PMID- 30277303
TI  - Outcomes following resection of non-small cell lung cancer in octogenarians.
AB  - BACKGROUND: The treatment of choice for early stage non-small cell lung cancer
      (NSCLC) is surgical resection. Little is known about the short- and long-term
      outcomes among very elderly patients. We sought to determine predictors of short-
      and long-term survival among octogenarians undergoing curative-intent resection
      for NSCLC in Victoria, Australia. METHODS: We retrospectively reviewed data from
      all patients aged >=80 years who underwent curative-intent resection for NSCLC
      over 12 years (January 2005-December 2016) across five tertiary centres. We
      examined effect of age, stage of disease, extent of surgery and lung function on
      short- and long-term survival. RESULTS: Two hundred patients aged >=80 years
      underwent curative-intent resections. Mortality at 30 and 120 days was 2.9% and
      5.9%, respectively. Increased early mortality was observed among those >=83
      years, at 30 days (6.8% versus 0.8%, P = 0.044) and 120 days (12.2% versus 2.3%,
      P = 0.0096). Early mortality was highest among patients >=83 years requiring
      lobectomy, compared to sub-lobar resection at 120 days (17% versus 3.8%, P =
      0.019). Long-term survival was predicted by age and stage of disease. Among
      patients with Stage I disease aged <83 years, lobectomy was associated with
      superior 5-year survival, compared to sub-lobar resection (83% versus 61%, P =
      0.02). CONCLUSION: In carefully selected elderly patients undergoing curative
      intent resection of early stage NSCLC, both short- and long-term outcomes appear
      consistent with younger historical cohorts. Early mortality was associated with
      lobectomy in those with advanced age. Older patients undergoing lobectomy
      appeared to be at highest risk for early mortality, while younger patients with
      Stage I disease undergoing at least lobectomy appear to have the best long-term
      survival.

PMID- 30277304
TI  - Solid-Phase Conversion of Four Stereoisomers into a Single Enantiomer.
AB  - Viedma ripening is an emerging method for the solid-phase deracemization of
      mixtures of enantiomers. Up to now, the scope of the method has remained limited
      to molecules with a single stereocenter. We show here that this method can be
      extended to obtain a single enantiomer from a mixture of stereoisomers with two
      different stereocenters. In addition, we show that by using tailor-made chiral
      additives, the conversion time can be reduced by a factor of 100.

PMID- 30277305
TI  - Kleptoplastidic benthic foraminifera from aphotic habitats: insights into
      assimilation of inorganic C, N and S studied with sub-cellular resolution.
AB  - The assimilation of inorganic compounds in foraminiferal metabolism compared to
      predation or organic matter assimilation is unknown. Here, we investigate
      possible inorganic-compound assimilation in Nonionellina labradorica, a common
      kleptoplastidic benthic foraminifer from Arctic and North Atlantic sublittoral
      regions. The objectives were to identify the source of the foraminiferal
      kleptoplasts, assess their photosynthetic functionality in light and darkness and
      investigate inorganic nitrogen and sulfate assimilation. We used DNA barcoding of
      a ~ 830 bp fragment from the SSU rDNA to identify the kleptoplasts and correlated
      transmission electron microscopy and nanometre-scale secondary ion mass
      spectrometry (TEM-NanoSIMS) isotopic imaging to study 13 C-bicarbonate, 15 N
      ammonium and 34 S-sulfate uptake. In addition, respiration rate measurements were
      determined to assess the response of N. labradorica to light. The DNA sequences
      established that over 80% of the kleptoplasts belonged to Thalassiosira (with 96%
      99% identity), a cosmopolitan planktonic diatom. TEM-NanoSIMS imaging revealed
      degraded cytoplasm and an absence of 13 C assimilation in foraminifera exposed to
      light. Oxygen measurements showed higher respiration rates under light than dark
      conditions, and no O2 production was detected. These results indicate that the
      photosynthetic pathways in N. labradorica are not functional. Furthermore, N.
      labradorica assimilated both 15 N-ammonium and 34 S-sulfate into its cytoplasm,
      which suggests that foraminifera might have several ammonium or sulfate
      assimilation pathways, involving either the kleptoplasts or bona fide
      foraminiferal pathway(s) not yet identified.

PMID- 30277306
TI  - Exosomes from human placenta purified by affinity chromatography on sepharose
      bearing immobilized antibodies against CD81 tetraspanin contain many peptides and
      small proteins.
AB  - Exosomes are nanovesicles (40-100 nm) containing various RNAs and different
      proteins. Exosomes are involved in intracellular communication and immune system
      function. Exosomes from different sources are usually isolated using standard
      methods-centrifugation and ultracentrifugations. Exosomes isolated by these
      procedures were reported to contain from a few dozen to thousands of different
      proteins. Here crude vesicle preparations from five placentas (normal pregnancy)
      were first obtained using standard centrifugation procedures. According to
      electron-microscopic studies, these preparations contained vesicles of different
      size (30-225 nm), particles of round shape of average electron density
      ("nonvesicles" 20-40 nm) (A), structured clusters of associated proteins and
      shapeless aggregations (B), as well as ring-shaped 10-14 nm structures formed by
      ferritin (C). After additional purification of the vesicle preparations by gel
      filtration on Sepharose 4B, the main part of protein structures was removed;
      however, the preparations still contained small admixtures of components A-C.
      Further purification of the preparations by affinity chromatography on Sepharose
      bearing immobilized antibodies against exosome surface protein CD81 led to
      isolation of highly purified exosomes (40-100 nm). These exosomes according to
      electron microscopy data contained tetraspanin embedded in the membrane, which
      was stained with antibodies against CD81 conjugated with 10-12 nm gold
      nanoparticles. SDS-PAGE and MALDI MS and MS/MS mass spectrometry of tryptic
      hydrolysates of proteins contained in these exosomes revealed eleven major
      proteins (>10 kDa): hemoglobin subunits, CD81, interleukin-1 receptor, annexin
      A5, cytoplasmic actin, alpha-actin-4, alkaline phosphatase, human serum albumin,
      serotransferrin, and lactotrasferrin. Using MALDI mass analysis of the highly
      purified exosomes, we for the first time found that in addition to the large
      proteins (>10 kDa), exosomes having affinity to CD81 contain more than 27
      different peptides and small proteins of 2-10 kDa. This finding can be useful for
      revealing biological functions of pure exosomes. (c) 2018 IUBMB Life, 70(11):1144
      1155, 2018.

PMID- 30277307
TI  - Perfluorooctanoic acid disrupts gap junction intercellular communication and
      induces reactive oxygen species formation and apoptosis in mouse ovaries.
AB  - Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acid family of
      compounds. Due to the presence of strong carbon-fluorine bonds, it is practically
      nonbiodegradable and highly persistent in the environment. PFOA has been detected
      in the follicular fluid of women, and positively associated with reduced
      fecundability and infertility. However, there are no reports concerning the
      experimental evaluation of PFOA on oocyte toxicity in mammals. The aim of the
      present study was to determine if PFOA is able to induce oxidative stress in
      fetal ovaries and cause apoptosis in oocytes in vitro. In addition, since
      inhibition of the gap junction intercellular communication (GJIC) by PFOA has
      been demonstrated in liver cells in vivo and in vitro, the effect of PFOA on the
      GJIC between the oocyte and its supportive cumulus cells was studied. Results
      show that PFOA induced oocyte apoptosis and necrosis in vitro (medium lethal
      concentration, LC50 = 112.8 MUM), as evaluated with Annexin-V-Alexa 508 in
      combination with BOBO-1 staining. Reactive oxygen species (ROS) levels, as
      assessed by DCFH-DA, increased significantly in fetal ovaries exposed to 1/4 LC50
      (28.2 MUM, a noncytotoxic and relevant occupational exposure concentration) and
      LC50 PFOA ex vivo. This perfluorinated compound also caused the blockage of GJIC
      in cumulus cells-oocyte complexes (COCs) obtained from female mice exposed in
      vivo, as evaluated by calcein transfer from cumulus cells to the oocyte. The
      ability of PFOA of disrupting the GJIC in COCs, generating ROS in the fetal ovary
      and causing apoptosis and necrosis in mammal's oocytes, might account for the
      reported association between increasing maternal plasma concentrations of PFOA
      with reduced fertility in women.

PMID- 30277308
TI  - Novel T4 bacteriophages associated with black band disease in corals.
AB  - Research into causative agents underlying coral disease have focused primarily on
      bacteria, whereas potential roles of viruses have been largely unaddressed.
      Bacteriophages may contribute to diseases through the lysogenic introduction of
      virulence genes into bacteria, or prevent diseases through lysis of bacterial
      pathogens. To identify candidate phages that may influence the pathogenicity of
      black band disease (BBD), communities of bacteria (16S rRNA) and T4
      bacteriophages (gp23) were simultaneously profiled with amplicon sequencing among
      BBD-lesions and healthy-coral-tissue of Montipora hispida, as well as seawater
      (study site: the central Great Barrier Reef). Bacterial community compositions
      were distinct among BBD-lesions, healthy coral tissue and seawater samples, as
      observed in previous studies. Surprisingly, however, viral beta diversities based
      on both operational taxonomic unit (OTU)-compositions and overall viral community
      compositions of assigned taxa did not differ statistically between the BBD
      lesions and healthy coral tissue. Nonetheless, relative abundances of three
      bacteriophage OTUs, affiliated to Cyanophage PRSM6 and Prochlorococcus phages P
      SSM2, were significantly higher in BBD-lesions than in healthy tissue. These OTUs
      associated with BBD samples suggest the presence of bacteriophages that infect
      members of the cyanobacteria-dominated BBD community, and thus have potential
      roles in BBD pathogenicity.

PMID- 30277309
TI  - Factors influencing pigment production by halophilic bacteria and its effect on
      brine evaporation rates.
AB  - The disposal of reject brine, a highly concentrated waste by-product generated by
      various industrial processes, represents a major economic and environmental
      challenge. The common practice in dealing with the large amounts of brine
      generated is to dispose of it in a pond and allow it to evaporate. The rate of
      evaporation is therefore a key factor in the effectiveness of the management of
      these ponds. The addition of various dyes has previously been used as a method to
      increase the evaporation rate. In this study, a biological approach, using
      pigmented halophilic bacteria (as opposed to chemical dyes), was assessed. Two
      bacteria, an Arthrobacter sp. and a Planococcus sp. were selected due to their
      ability to increase the evaporation of synthetic brine. When using industrial
      brine, supplementation of the brine with an iron source was required to maintain
      the pigment production. Under these conditions, the Planococcus sp. CP5-4
      produced a carotenoid-like pigment, which resulted in a 20% increase in the
      evaporation rate of the brine. Thus, the pigment production capability of
      halophilic bacteria could potentially be exploited as an effective step in the
      management of industrial reject brines, analogous to the crystallizer ponds used
      to mine salt from sea water.

PMID- 30277310
TI  - The role of compatible solutes in desiccation resistance of Acinetobacter
      baumannii.
AB  - Acinetobacter baumannii is a nosocomial pathogen which can persist in the
      hospital environment not only due to the acquirement of multiple antibiotic
      resistances, but also because of its exceptional resistance against disinfectants
      and desiccation. A suitable desiccation assay was established in which A.
      baumannii ATCC 19606T survived for ca. 1 month. The growth medium slightly
      influenced survival after subsequent desiccation. A significant effect could be
      attributed to the growth phase in which bacteria were dried: In exponential
      phase, cells were much more desiccation sensitive. The main focus of the present
      study was the elucidation of the role of compatible solutes, which are known to
      protect many bacteria under low water activity conditions, in desiccation
      survival of A. baumannii. Exogenous trehalose was shown to efficiently protect A.
      baumannii on dry surfaces, in contrast to other compatible solutes tested such as
      mannitol or glycine betaine. To analyze the importance of intracellularly
      accumulated solutes, a double mutant lacking biosynthesis pathways for mannitol
      and trehalose was generated. This mutant accumulated glutamate as sole solute in
      the presence of high NaCl concentrations and showed severe growth defects under
      osmotic stress conditions. However, no effect on desiccation tolerance could be
      seen, neither when cells were dried in water nor in the presence of NaCl.

PMID- 30277311
TI  - World Health Organization life-skills training is efficacious in reducing youth
      self-report scores in primary school going children in Kenya.
AB  - AIM: Documented evidence shows that training in life skills for school going
      children improves their physical and mental health status. Although Kenya has a
      curriculum and a policy for life-skills training in schools, these have not been
      implemented because lack of local evidence for efficacy. Therefore, the objective
      of this study was to determine the efficacy and effectiveness of the life-skill
      training curriculum for primary schools developed by the Ministry of Education,
      Kenya. METHODS: We randomly selected 23 schools from two randomly selected sub
      counties representing urban/peri-urban and rural contexts in Kenya. We collected
      baseline socio-demographic characteristics and administered the locally validated
      youth self-report (YSR) for 11 to 18 years old at baseline and 9 months post
      intervention. We used the Ministry of Education validated curriculum for life
      skills training for upper primary school as the intervention immediately after
      the baseline. RESULTS: The World Health Organization life-skills training is
      efficacious in reducing YSR scores in primary school going children in Kenya. We
      found that socio-demographic characteristics were predictors for mental health
      and that there were significant positive improvements in internalizing and
      externalizing YSR symptoms and syndromes in both sites. The improvement was over
      40% and therefore unlikely to be attributable to placebo effect or natural
      recovery without intervention. However, attention problems worsened more so in
      rural sites and particularly in girls. CONCLUSIONS: Life-skills training is
      efficacious in improving mental health in school going children in the Kenyan
      context. However, it is not effective in attention problems which seem to be
      cognitive in nature.

PMID- 30277312
TI  - Recent Advancements in Graphene-Based Supports of Metal Complexes/Oxides for
      Epoxidation of Alkenes.
AB  - In the past decade, there has been great progress in the preparation and
      catalytic applications of graphene-supported metal complexes/oxide catalysts.
      Graphene-based materials have attracted tremendous research interest owing to
      special physicochemical properties, for example, unique two-dimensional
      structure, high theoretical specific surface area, high electrical conductivity,
      and outstanding acid-base resistance properties. Graphene-supported metal
      complexes/oxides have been extensively investigated, and exhibit good catalytic
      activity and stability in water splitting (H2 generation or oxygen evolution),
      oxidation/epoxidation of alkenes, C-C bond formation, and so forth. Herein,
      recent developments in graphene-supported metal complexes/oxides for the
      catalytic epoxidation of different alkenes are summarized. Site isolation and
      synergistic interactions between metal complexes/oxides and graphene are the two
      key roles for enhancing the catalytic activity, whereas the hydrophobicity of the
      support can efficiently improve epoxide selectivity. In addition, the possible
      mechanisms of catalytic epoxidation are summarized. This review provides a
      feasible scheme for the potential application of graphene-based materials and
      guidance for the rational design of heterogeneous catalysts for catalytic
      applications.

PMID- 30277313
TI  - General practitioners' views towards diagnosing and treating depression in five
      southeastern European countries.
AB  - AIM: To assess and compare general practitioners' (GPs') views of diagnosing and
      treating depression in five southeastern European countries. METHODS: A cross
      sectional study was conducted in Albania, Bulgaria, Moldova, Romania, and Serbia.
      The sample included 467 GPs who completed a hard-copy self-administered
      questionnaire, consisting of self-assessment questions related to diagnosing and
      treating depression. RESULTS: The most common barriers to managing depression in
      general practice reported by GPs were: patients' unwillingness to discuss
      depressive symptoms (92.3%); appointment time too short to take an adequate
      history (91.9%), barriers for prescribing appropriate treatment (90.6%); and
      patients' reluctance to be referred to a psychiatrist (89.1%). Most GPs (78.4%)
      agreed that recognizing depression was their responsibility, 71.7% were confident
      in diagnosing depression, but less than one-third (29.6%) considered that they
      should treat it. CONCLUSIONS: Improvements to the organization of mental
      healthcare in all five countries should consider better training for GPs in
      depression diagnosis and treatment; the availability of mental healthcare
      specialists at primary care level, with ensured equal and easy access for all
      patients; and the removal of potential legal barriers for diagnosis and treatment
      of depression.

PMID- 30277314
TI  - Glucose metabolism dysregulation at the onset of mental illness is not limited to
      first episode psychosis: A systematic review and meta-analysis.
AB  - AIM: To compare the differences of glucose metabolism outcomes between treatment
      naive, patients with first episode psychosis (FEP) and mood disorders. METHODS:
      We conducted a systematic review and meta-analysis of glucose intolerance in
      treatment-naive, first episode patients with severe mental illnesses (SMIs).
      RESULTS: We identified 31 eligible studies. Compared to healthy controls, FEP
      group have higher insulin and insulin resistance levels, and both groups have
      higher glucose tolerance test results. No significant differences were found in
      glucose metabolism outcomes between FEP and mood disorder groups. CONCLUSIONS:
      Our results highlight impaired glucose metabolism at the onset of SMIs,
      suggesting both patients with psychosis and mood disorders are high-risk groups
      for diabetes development.

PMID- 30277315
TI  - Cryptococcal antigenemia and associated risk factors among ART-naive and ART
      experienced HIV-infected peoples at selected health institutions of Mekelle,
      Northern Ethiopia.
AB  - Cryptococcal infection is a major cause of opportunistic infection in HIV/AID
      infected peoples. We determined cryptococcal antigenemia and cryptococcal
      meningitis among antiretroviral therapy (ART) initiated and ART-naive HIV
      infected peoples. A cross-sectional study was conducted at selected health
      facilities in Mekelle, Ethiopia. Blood was collected to determine CD4 and plasma
      cryptococcal antigen (CrAg). CSF CrAg and CSF culture and urease tests were also
      done. Socio-demographic and clinical data were collected using a structured
      questionnaire and clinical chart review. From the enrolled study participants,
      267 study participants had complete data, of which, 137 (51%) were females. From
      the study participants, 140 (52%) and 127 (48%) were ART experienced and ART
      naive, respectively. The prevalence of cryptococcal antigenemia was 9 (3.4%). All
      the study participants, except one (CD4 = 120 cells/mm3 ), had CD4 count less
      than 100 cells/mm3 . From CrAg-positive peoples, 6 (4.7%) were ART naive. Five
      CrAg-positive peoples had cryptococcal meningitis. Being male, rural residence,
      and being hospitalized were associated with cryptococcal antigenemia.
      Cryptococcal infection poses a substantial risk of HIV-positive peoples. This
      study provides relevant data for CrAg screening interventions in patients with
      low CD4 cell counts.

PMID- 30277316
TI  - Effects of a school teacher-led 45-minute educational program for mental health
      literacy in pre-teens.
AB  - AIM: A concise teacher-led program for mental health literacy (MHL), suitable for
      schools with tight schedules was developed, and its effects were examined in pre
      teens. METHODS: Participants comprised 662 grade 5 to 6 students from nine
      Japanese elementary schools. The program consisted of a 45-minute session,
      delivered by school teachers using a 10-minute animated film. Program focuses
      included: mental health problems are common, can be associated with lifestyle and
      that seeking help from reliable adults is a key to finding solutions.
      Participants filled out self-report questionnaires before, immediately after and
      3 months post-intervention. Changes in MHL were analyzed using multilevel models.
      RESULTS: Knowledge about mental health/illnesses, recognition of mental health
      state and intention to help peers/seek help when suffering from mental health
      problems, were significantly improved immediately and 3 months post-intervention.
      CONCLUSIONS: Concise teacher-led programs administered in schools can have
      positive and lasting effects on MHL in pre-teens.

PMID- 30277317
TI  - Academic achievement and employment in young adults with end-stage kidney
      disease.
AB  - BACKGROUND: Young adults with end-stage kidney disease (ESKD) are at a pivotal
      stage of life: progressing through education, seeking employment and developing
      relationships. We set out to explore how ESKD impacts education and employment
      attainment in a matched UK and USA patient cohort. Moreover, we aimed to
      determine if there were significant differences in reported perceptions of
      impact. DESIGN: A mixed methods design combining previously validated
      quantitative questionnaire surveys and qualitative semi-structured interviews.
      PARTICIPANTS: Young people with ESKD aged 18-30 years (N = 27), attending single
      centre follow-up in Oxford, UK were matched with 27 comparable young people aged
      19-30 years, under follow-up in Denver, USA. Twelve of these patients from Denver
      were selected for interview. MEASUREMENTS: Self-report questionnaires surveyed
      patient demographics, educational and employment achievement and experiences.
      Questionnaire categorical data for matched pairs were analysed using Bowker's
      test of symmetry. Sequential flow analyses of interview content delineated
      perception patterns through thematic coding. RESULTS: Sixty percent of non
      student Oxford participants were employed compared with 41% in Denver (p =
      0.023). Forty-four percent of Oxford patients compared with 52% in Denver,
      reported illness had made it difficult to gain employment (p = 0.88). In Oxford,
      32% completed high school as their highest educational achievement, versus 68% in
      Denver (p = 0.22). Qualitative themes included fatigue, self-esteem loss, social
      isolation and low mood. The impact of dialysis and poor understanding from
      educators/employers resulted in lost work time, and/or limited educational
      attainment. CONCLUSION: ESKD profoundly impacts on education and employment of
      young adults in the United States and United Kingdom, generating substantial
      barriers. Poor understanding appears prevalent amongst educators and employers.
      Healthcare providers must recognise these problems and invest resources towards
      tailored support in order to improve associated psychosocial and clinical
      outcomes.

PMID- 30277318
TI  - Attaining High Photovoltaic Efficiency and Stability with Multidimensional
      Perovskites.
AB  - The power conversion efficiency of organic-inorganic hybrid perovskite solar
      cells has soared over the past ten years and currently rivals those of
      crystalline silicon and other thin-film solar cells. Most of the research effort
      so far has been focused on three-dimensional (3 D) perovskite crystals, producing
      devices with very high efficiency but poor operational and environmental
      stability. Two-dimensional (2 D) Ruddlesden-Popper perovskite has recently shown
      its potential as a highly stable light absorber, albeit with low efficiency. This
      work reviews the current progress in attaining both high efficiency and stability
      in solar cells by using 2 D perovskite. In particular, the focus is on
      multidimensional perovskite as a way to combine the best characteristics of 3 D
      and 2 D perovskites. Future challenges and potential methods to boost the
      performance of multidimensional perovskite solar cells further are briefly
      presented.

PMID- 30277319
TI  - Contribution of structural recalcitrance to the formation of the deep oceanic
      dissolved organic carbon reservoir.
AB  - The origin of the recalcitrant dissolved organic carbon (RDOC) reservoir in the
      deep ocean remains enigmatic. The structural recalcitrance hypothesis suggests
      that RDOC is formed by molecules that are chemically resistant to bacterial
      degradation. The dilution hypothesis claims that RDOC is formed from a large
      diversity of labile molecules that escape bacterial utilization due to their low
      concentrations, termed as RDOCc . To evaluate the relative contributions of these
      two mechanisms in determining the long-term persistence of RDOC, we model the
      dynamics of both structurally recalcitrant DOC and RDOCc based on previously
      published data that describes deep oceanic DOC degradation experiments. Our
      results demonstrate that the majority of DOC (84.5 +/- 2.2%) in the deep ocean is
      structurally recalcitrant. The intrinsically labile DOC (i.e., labile DOC that
      rapidly consumed and RDOCc ) accounts for a relatively small proportion and is
      consumed rapidly in the incubation experiments, in which 47.8 +/- 3.2% of labile
      DOC and 21.9 +/- 4.6% of RDOCc are consumed in 40 days. Our results suggest that
      the recalcitrance of RDOC is largely related to its chemical properties, whereas
      dilution plays a minor role in determining the persistence of deep-ocean DOC.

PMID- 30277320
TI  - Impact of Phaeobacter inhibens on marine eukaryote-associated microbial
      communities.
AB  - Bacteria-host interactions are universal in nature and have significant effects
      on host functionality. Bacterial secondary metabolites are believed to play key
      roles in such interactions as well as in interactions within the host-associated
      microbial community. Hence, prominent secondary metabolite-producing bacteria may
      be strong drivers of microbial community composition in natural host-associated
      microbiomes. This has, however, not been rigorously tested, and the purpose of
      this study was to investigate how the secondary metabolite producer Phaeobacter
      inhibens affects the diversity and composition of microbiomes associated with the
      microalga Emiliania huxleyi and the European flat oyster, Ostrea edulis.
      Roseobacters were indigenous to both communities exhibiting relative abundances
      between 2.8% and 7.0%. Addition of P. inhibens caused substantial changes in the
      overall structure of the low-complexity microbiome of E. huxleyi, but did not
      shape microbial community structure to the same degree in the more complex oyster
      microbiomes. Species-specific interactions occurred in both microbiomes and
      specifically the abundances of other putative secondary metabolite-producers such
      as vibrios and pseudoalteromonads were reduced. Thus, the impact of a bioactive
      strain like P. inhibens on host-associated microbiomes depends on the complexity
      and composition of the existing microbiome.

PMID- 30277321
TI  - Absence of infratentorial lesions in Fabry disease contributes to differential
      diagnosis with multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Multiple Sclerosis (MS) has been proposed as a possible
      differential diagnosis with Fabry Disease (FD). We evaluated the incidence of
      infratentorial lesions in FD patients, investigating whether their presence could
      help in differentiating these two conditions. We explored the diagnostic accuracy
      of this sign alone and in combination to the involvement of corpus callosum (CC).
      METHODS: White Matter lesions were retrospectively evaluated on FLAIR images
      available from 136 MS and 144 FD patients. Infratentorial involvement was
      assessed considering the whole cerebellum, and the part of the brainstem included
      between the occipital foramen and the upper edge of the red nucleus. Furthermore,
      the presence of callosal lesions was also recorded, evaluating the portion of CC
      included between the two external walls of the lateral ventricles. RESULTS:
      Infratentorial involvement was detectable in 119/136 (87.5%) MS patients, while
      it was present in only 17/144 (11.8%) FD patients. When the diagnostic
      performance of a positive infratentorial involvement was evaluated in combination
      with the presence of CC lesions, a specificity of 97%, with a positive predictive
      value of 96% was reached. CONCLUSIONS: We concluded that the absence of
      infratentorial lesions, especially when combined to the evaluation of other
      typical imaging features, can help in the differential diagnosis between MS and
      FD.

PMID- 30277323
TI  - Excelling at the 'People Business'.

PMID- 30277322
TI  - Solar Photothermal Electrodes for Highly Efficient Microbial Energy Harvesting at
      Low Ambient Temperatures.
AB  - Temperature is an important parameter for the performance of bioelectrochemical
      systems (BESs). Energy-intensive bulk water heating has been usually employed to
      maintain a desired temperature for the BESs. This study concerns a proof-of
      concept of a light-to-heat photothermal electrode for solar heating of a local
      electroactive biofilm in a BES for efficient microbial energy harvesting at low
      temperatures as a replacement for bulk water heating approaches. The photothermal
      electrode was prepared by coating Ti3 C2 Tx MXene sunlight absorber onto carbon
      felt. The as-prepared photothermal electrode could efficiently raise the local
      temperature of the bioelectrode to approximately 30  degrees C from low bulk
      water temperatures (i.e., 10, 15, and 20  degrees C) under simulated sunlight
      illumination. As a result, highly efficient microbial energy could be harvested
      from the low-temperature BES equipped with a photothermal electrode without bulk
      water heating. This study represents a new avenue for the design and fabrication
      of electrodes for temperature-sensitive electrochemical and biological systems.

PMID- 30277324
TI  - Spring Forward to Protect Patient Care.

PMID- 30277325
TI  - SEEKING HELP: Engaging the community critical to transition toward a wellness
      society.

PMID- 30277326
TI  - WORKING OVERTIME: Creative ways to cut skilled labor costs.

PMID- 30277327
TI  - SIGNS OF HOPE: Quality efforts may be narrowing disparities.

PMID- 30277328
TI  - CLASSROOM EXPERIENCE: Teaching future leaders about the patient experience.

PMID- 30277329
TI  - MOST WIRED: Business intelligence and financial risk.

PMID- 30277330
TI  - TELEHEALTH Reshaping Your World and Your Patients'.

PMID- 30277331
TI  - A Powerful Push to Pay for Value.

PMID- 30277332
TI  - Whol's Patient Is He, Anyway? Attribution, the process of assigning patients to
      physicians in population health programs, aims to answer that question.

PMID- 30277333
TI  - Built Tougher Hospitals turn to 'resilient design' after a series of natural
      disasters.

PMID- 30277334
TI  - GREENING the OR.

PMID- 30277335
TI  - The Value Proposition.

PMID- 30277336
TI  - Governance of Physician Organizations: An Essential Step to Care Integration.

PMID- 30277337
TI  - PCP EXCELLENCE 10 traits shared by the country's best primary care practices.

PMID- 30277338
TI  - APP HAPPY Keeping up with the patients.

PMID- 30277339
TI  - A NEW PAL A little more conversation.

PMID- 30277340
TI  - MOST WIRED Being proactive with population-based disease registries.

PMID- 30277341
TI  - SUBSIDY THREAT The Supreme Court's next big ACA ruling.

PMID- 30277342
TI  - CONSUMERISM Hits Health Care.

PMID- 30277343
TI  - Thirty-something and the CEO.

PMID- 30277344
TI  - Hospitals muscle up on 'MEDICAL FITNESS' Akron General Health System leads a
      national movement to build centers that promote wellness and prevention and boost
      branding.

PMID- 30277345
TI  - An SOS on Cybersecurity To protect patient data, hospitals beef up risk
      management programs. Hello, chief security officers and 'white hat hackers'.

PMID- 30277346
TI  - Multidisciplinary team attitudes to an advanced nurse practitioner service in an
      emergency department.
AB  - AIM: The aim of this study was to examine an emergency department's (ED)
      multidisciplinary teams' (MDTs) attitudes towards an advanced nurse practitioner
      (ANP) service. The ED in question is not the author's place of work. METHOD: A
      Likert-type questionnaire was used to gain a total attitude score (TAS), which
      was analysed in relation to participants' gender, age, professional background,
      level of education and years of experience in the ED, as well as previous and
      current contact with emergency nurse practitioners and/or ANPs. A total of 115
      questionnaires were distributed, and respondents included doctors, nurses,
      managers, pharmacists, radiographers and a physiotherapist. Participants provided
      qualitative data to explain their choices, and were asked to describe positive
      and negative aspects of an ANP service. The data were analysed using a mixed
      methods approach. FINDINGS: The TASs were generally positive and there were no
      statistical differences between the professional groups, although there was some
      resistance from participants. CONCLUSION: Overall, the MDT believes the ANP
      service will improve patient care, waiting times, team divisions and patients'
      experiences in the ED if the roles and responsibilities are clearly defined and
      communicated. In addition, the service should receive enough funding to ensure
      its sustainability and appropriate supervision by a senior doctor should be made
      available.

PMID- 30277347
TI  - [Use of Fundamental Properties of Embryonic Objects for Studying Potential
      Environmental Effects of Technogenic Impacts].
AB  - This article analyzes the problems of biosafety in terms of individual
      development patterns. Previously,the key role of epigenetic free radical
      processes in normal embryonic development of lower vertebratesin the formation of
      the competence and determination of embryonic primordia has been demonstrated,
      anda significant increase in the intensity of free radical process before every
      qualitative change in homeostaticmechanisms in developing organisms was found: in
      induction systems, before hatching of the embryo fromthe shells, and in
      preparation for metamorphosis. Thus, the activation of free radical processes in
      embryonicprimordia corresponds to instability and characterizes the "critical
      periods of development" and increasedsensitivity of the embryo to environmental
      impacts. Patented methods and a test system that allows detectingearly biological
      effects of weak environmental impacts and predicting their environmental risk are
      presented.Possible mechanisms of significant biological effects of weak radiation
      and chemical impacts on the developingorganism are discussed. The necessity of
      including embryonic objects in the protocol of testing the biosafetyof
      technological developments is substantiated.

PMID- 30277348
TI  - [Regeneration of the Skin Pigment System during Larval Development of the Clawed
      Frog].
AB  - We demonstrate regeneration capability of the skin pigment system of clawed frog
      larvae after localdamage to melanophores without skin rupture. The contribution
      to recovery of pigmentation of the injuredarea of de novo differentiation of
      melanophores is compared to contribution of mitotic division of
      undamagedmelanophores localized on the boundaries of the injured area. The
      regeneration process is observed duringvarious stages of pigment system
      development of larvae. We establish that, compared to ontogenetic
      dynamics,pigmentation development in animals is more intense during the
      regeneration.

PMID- 30277349
TI  - [APPLICATION OF ALLOGENIC TISSUE OF THE FETAL BRAIN CORTEX AND THE OLFACTORY BULB
      TISSUE FOR TREATMENT OF THE BRAIN CONTUSION IN RATS].
AB  - Impact of the allogenic tissue transplantation of the fetal cerebral large
      hemispheres and the olfactory bulb tissue (OBT) on the healing processes after
      the brain contusion was studied in experiment. The investigation was performed on
      mongrel male rats: in laboratory animals of the first group in the first day
      after open penetrating local cerebral trauma (OPLCT) the allogenic fetal nervous
      tissue fragment was transplanted into the formatted tissue defect; for the second
      group - in the first day after cerebral trauma the allogenic OBT fragment was
      transplanted into the formatted tissue defect; and for the third group (control) 
      the OPLCT was done without further transplantation of tissues. The impact of the
      allogenic fetal nervous tissue transplantation was demonstrated by more active
      participation of glial cells during the healing process course, and the OBT
      transplantation was followed by activation of neoangiogenesis processes , mainly
      in the injured brain. The experimental simulation choosed permits to study the
      possibilities of application of neurogenic tissues in the brain contusion
      treatment, and to determine the therapy tactics.

PMID- 30277350
TI  - [THE CHANGES OF CLINICAL APPROACHES AND TACTICS OF TREATMENT IN ACUTE
      PANCREATITIS, TAKING INTO ACCOUNT THE REVIEWED ATLANTA 2012 CLASSIFICATION].

PMID- 30277351
TI  - [OBSERVATION OF SIMULTANT EXCISION OF RETROPERITONEAL SARCOMA, AORTO-FEMORAL
      BIFURCATION ALLOSHUNTING AND A RIGHT-SIDED HEMICOLECTOMY].

PMID- 30277352
TI  - [THE STAGED ENDOVASCULAR TREATMENT OF THE ABDOMINAL AND THORACIC AORTAL ANEURYSM
      IN ONE PATIENT].

PMID- 30277353
TI  - [ANALYSIS OF DIAGNOSTIC MISTAKES WHILE HEPATIC ABSCESS OCCURRENCE].

PMID- 30277354
TI  - [CLINICAL OBSERVATION OF THE ESOPHAGEAL DIVERTICULUM COMPLICATION].

PMID- 30277355
TI  - ?

PMID- 30277356
TI  - [THE EXPERTS CONSENSUS FOR ANTICOAGULANT THERAPY OF VENOUS THROMBOEMBOLISM IN
      2016 YR. SIGNIFICANCE OF THE RIVAROXABAN INVESTIGATIONS PROGRAM FOR CHANGES OF
      APPROACHES, CONCERNING TREATMENT OF THE DEEP VEINS THROMBOSIS AND PULMONARY
      THROMBOEMBOLISM].

PMID- 30277357
TI  - [PLASTIC CLOSURE OF THE WOUND DEFECT IN PATIENTS, SUFFERING THE ORAL AND ORO
      PHARYNGEAL CANCER STAGES III - IV].
AB  - Results of treatment of 124 patients, suffering locally-advanced oral and
      oropharyngeal cancer were analyzed. In these patients after wide excision of
      tissues the defect has occurred, which would be impossible to close using simple
      suturing. To these patients a primary plasty, using musculo-cutaneous or adiposo
      cutaneous flap, was performed. The defect, occurring after resection of the oral
      cavity floor together with the mandibular anterior fragment, constitutes the most
      complex one for the plasty performance. The main principles of the defects plasty
      were determined. The plastic material choice depends on peculiar clinical
      situation, the surgical intervention volume, the defect localization and its
      size.

PMID- 30277358
TI  - [Reproductive Biology and a Genome Resource Bank of Felidae].
AB  - The main achievements in applying modern reproductive technologies to the banking
      of thegenetic resources of the Felidae family are reviewed. The classification of
      felids at the level of species and subspeciesis revised in the light of recent
      molecular data. Special emphasis is made on such mainstream technologiesas semen
      collection and cryopreservation followed by artificial insemination, as well as
      on in vitromaturation and fertilization of oocytes combined with the culture of
      in vitro-derived felid embryos.

PMID- 30277359
TI  - Tools to Face Burnout in Nursing: Social Support, Resilience and Coping
      Strategies.
AB  - Objectives: To establish the differences in social support, resilience, coping,
      and three burnout dimensions (emotional exhaustion, depersonalization, and
      reduced personal accomplishment) among special units nursing and nursing staff of
      others hospital services; as well as to determine psychological variables that
      predict burnout in these professionals. Method: Correlational and cross-sectorial
      study. A sample of 133 nursing professionals from University Hospital of
      Fuenlabrada (Madrid) took part in the study, of whom 61 worked in special units
      and 72 in wards. Instruments: Maslach Burnout Inventory-Human Services Survey
      (MBI-HSS), Social Support Subscale, 10-Item CD-RISC (resilience), Brief-Cope
      (coping), and sociodemographic variables. Results: No differences were found in
      any assessed psychological variables as regards hospital service worked in.
      Social support, resilience and coping strategies determined three burnout
      dimensions: social support (beta = -0.21, support coping (beta = -0.22) and
      disengagement coping (beta = 0.22) predicted emotional exhaustion; resilience (V
      = -0.22) and disengagement coping (beta = 0.30) predicted depersonalization; and
      engagement coping (beta = -0.55) predicted reduce personal accomplishment.
      Conclusions: Differences in burnout, social support, resilience and coping
      strategies are not determined by hospital service. Social support, resilience,
      engagement coping, and support coping (adaptives) constitute three tools to face
      burnout in nursing. These tools could be developed by specific programs from
      universities and health institutions to improve nursing clinical practice.

PMID- 30277360
TI  - [Developmental Aspects of Senescence].
AB  - Different types of senescence and major theories of aging are reviewed, and
      mechanisms of thiscomplex biological phenomenon are discussed. Emphasis is placed
      on changes in the nervous systems ofmammals and humans with age. Experimental
      animal models for studying aging and modern approaches tothe correction of age
      related deterioration are considered. Chemicals and other factors that may
      alleviate age-relateddisorders and slow down senescence are critically reviewed.

PMID- 30277361
TI  - [Environmental factors inducing the transformation of polyp into medusae in
      Aurelia aurita (Scyphozoa)].
AB  - The transformation of polyp into medusa is one of the most interesting processes
      in the life cycleof cnidarians. In the polyps of the class Scyphozoa this
      transformation occurs in the form of strobilation,which is the transverse fission
      of polyps with the formation of discoidal ephyrae. At present, the
      endogenousregulation of strobilation in one of scyphozoans, Aurelia aurita, is
      being investigated by the methods of molecularbiology (Fuchs et al., 2014).
      However, it is still unclear which key environmental factors induce this
      process.The main purposes of this review are to summarize the literature data on
      the conditions in which strobilationin A. aurita occurs in nature and in the
      laboratory and to try to identify the environmental factors thatare most likely
      to play a signaling role in strobilation.

PMID- 30277362
TI  - [Body Image Disturbances in Burned People: Nurse's Approach].
AB  - Background: The nursing diagnosis Body image disturbance is present in al the
      burned people. The approach of this diagnosis is a nursing responsibility, so
      nurses must carry out the assessment of the functional pattern Self-perception
      Self-concept knowing in depth the concepts of "self-concept" and "self-esteem".
      Aims: To identify the most effective nursing interventions to address the Body
      image disturbance. Method: A literature review has been made consulting the
      following databases PubMed, CINAHL, Cuiden, COCHRANE and PsychInfo. The main
      selected articles have been: randomized clinical trials, descriptive studies and
      literature reviews. Results: The proposed nursing care plan is based on a focused
      assessment of the functional pattern Self-perception-Self-concept using the
      Satisfaction With Appearance Scale and applying the nursing inverventions:
      Cognitive restructuring and Body image enhancement. Conclusions: Both assessment
      and interventions have shown to be based on evidence and being an effective way
      to take care of the Body image disturbance in the burned person.

PMID- 30277363
TI  - [Analysis of the Gamete-Fusion Genes in the Haploid-inducing ZMS-P Maize Line].
AB  - This article is devoted to the study of the double fertilization mechanism in
      plants, in particular ofthe maize gamete membrane fusion genes. We detected and
      analyzed for the first time gamete-fusion genesin the maize genome. Using the
      BLAST program, we searched for the hap2 gene (generative cell specific 1(gcs1))
      homologs from Arabidopsis in the maize genome. The ZM_BFb0162K03 maize transcript
      was found,which had 67% identity to the Athap2 gene and contained a conserved
      region similar to the Athap2 gene fragment.In mRNA samples from the haploid
      inducing and control maize lines, an PCR was conducted by usingprimers specific
      to the ZM_BFb0162K03 sequence fragment. Sequences of the PCR products from a
      fragment(1467 bp) of the Zm_hap2 gene of the haploid-inducing and the control
      maize lines were identical andalso were identical to the maize sequences from the
      GenBank (ZM_BFb0162K03). PCR products (656 bpregion of Zm_hap2) for the
      ZM_BFb0162K03 (1925 bp) maize sequence were observed for the cDNA of
      pollengrains, ovary, leaves, and roots of the haploid-inducing and control maize
      lines. Using the Blastx program,we found significant homology of the maize
      translated proteins to the GEX2, TET11, and TET12 proteins,involved in
      Arabidopsis gamete-fusion contacts.

PMID- 30277364
TI  - [Auxin Abolishes Inhibitory Effects of Methylcyclopropen and Amino Oxyacetic Acid
      on Pollen Grain Germination, Pollen Tube Growth, and the Synthesis of ACC in
      Petunia].
AB  - As established by us earlier, ethylene behaves as a regulator of germination,
      development, andgrowth of male gametophyte during the progamic phase of
      fertilization. However, the mechanisms of the regulationof these processes remain
      so far unstudied. It is believed that the main factor providing variety of
      theethylene responses is its interaction with other phytohormones. According to
      our working hypothesis, ethylenecontrols germination of pollen grains (PGs) and
      growth of pollen tubes (PTs) by interacting with auxin,which, as the available
      data indicate, is likely a key regulator of plant cell polarization and
      morphogenesis andone of the factors modulating the biosynthesis of ethylene at
      the level of ACC-synthase gene expression. Inthe present work, on germinating in
      vitro male gametophyte and the pollen-stigma system for petunia (Petuniahybrida
      L.) effects of phytohormones (ethylene and IAA) and known blockers repressing
      ethylene reception(1-methylcyclopropene, 1-MCP), the synthesis of ACC (amino
      oxyacetic acid, AOA) and transport IAA(triyodbenzoynaya acid, TYBA) on PGs
      germination, PTs growth and the synthesis of ACC were investigated.According to
      the data obtained, exogenous ethylene and IAA stimulated both PGs germination
      andPTs growth. 1-MCP and TYBA completely inhibited the first process, whereas IAA
      abolished the inhibitoryaction of 1-MCP and AOA on both the above processes.
      Etrel only partially weakened the inhibitory effect ofTYBA. Examination of ACC
      synthesis modulation with AOA showed that IAA does not affect the level ofACC in
      germinating in vitro male gametophyte and nonpollinated stigmas, while this
      phytohormone insignificantlyraised the level of ACC and abolished the inhibitory
      effect of AOA on its synthesis in the pollenstigmasystem. Pollination of stigmas
      with the pollen preliminarily treated with 1-MCP led to 2.5-fold declinein both
      the rate of PT growth and the level of ACC. At the same time, IAA abolished the
      inhibitory action of1-MCP recovering the synthesis of ACC and growth of PTs to
      the control values. All these results, takentogether, provide evidence for the
      interaction of the signal transduction pathways of ethylene and auxin at thelevel
      of ACC biosynthesis in the course of germination and growth of petunia male
      gametophyte during theprogamic phase of fertilization.

PMID- 30277365
TI  - [Early Peripheral Sensory Neurons in the Development of Trochozoan Animals].
AB  - Neuronal development of the majority of trochozoan animals with biphasic pelago
      bentic lifecycle starts from transient peripheral neurons, which do not belong to
      the central nervous system and aremainly located in the apical sensory organ and
      in the hyposphere. Some of these neurons are pioneer and sendneurites that form a
      scaffold upon which the adult central nervous system later develops. In
      representativespecies of molluscs and polychaetes, immunolabelling with the
      antibodies against neurotransmitters serotoninand FMRFamide, and acetylated alpha
      tubulin revealed that the structure of almost all early peripheralneurons is
      typical for sensory, most probably chemosensory cells: flask shape, and cilia at
      the end of the apicaldendrite or inside the distal ampoule. Morphology,
      transmitter specificity, location and projections of theearly sensory cells
      differ in trochophores of different species thus suggesting different origin of
      these cells. Inpolychaete larvae, pharmacological inhibition of serotonin
      synthesis in early peripheral neurons did not affectthe development, whereas its
      increase resulted in developmental arrest and neural malformations,
      suggestingthat early peripheral sensory neurons are involved in developmental
      regulation.

PMID- 30277366
TI  - [Dynamics of Reaching Imago Stage by F1 Animals after Terahertz Irradiation of
      Parental Drosophila].
AB  - Terahertz radiation (0.1-10 THz) is increasingly becoming a factor of human
      habitat. The studyof the consequences of radiation allows one to estimate its
      possible biological danger. Our data indicate thatthe terahertz irradiation of
      parental Drosophila shortens the period of embryonic development of their
      firstgeneration descendants. Significant deviations of data from the control were
      found, when both females andmales were experimental parents. The highest portion
      of animals with accelerated hatching as compared withthe control was found in
      progenies from irradiated females. The shift of maximal hatching peak to an
      earlierperiod was found in descendants of both sexes. Thus, it was for the first
      time found on the model object (Drosophila)that the terahertz irradiation of
      parents can have positive or negative consequences in the first
      generationdescendants.

PMID- 30277367
TI  - [Onthogenetic Polyvariaty in the Representatives of Trifolium L. Genus Lupinaster
      (Fabr.) Ser. Section].
AB  - The progress of ontogenesis is analyzed in four members of the genus Trfolium,
      Lupinaster sectionand it is shown that the ecological conditions have a guiding
      influence on the course of individual developmentof the species. The most
      important among them are: soil mechanical composition, distance from theseashore,
      regime and intensity of moistening. Six variants of the ontogenesis, having two
      subvariants for threeof them, were allocated for the members of the section. The
      initial stages of the ontogenesis are similar, butthe main differences begin to
      manifest from the virginal age. Evolutionary transformation within the sectionare
      expressed in reduced leaflets of compound leaves, weakened functioning of the
      main root, rhizome development,and the transition of perennial forms to
      vegetative biennials.

PMID- 30277368
TI  - [Validation of the Nursing Assessment System of the Pediatric Primary Care
      Emergency: VEUPAP].
AB  - Objective: Measure the validity, reliability and consistency of two alternative
      diagnostic systems, Nurse Pediatric Emergency Assessment for Primary Care system
      (VEUPAP) and web_e-PAT(r), using expert pediatricians judgment as a gold
      standard. Material and Methods: Random sample of 300 children aged 0-14 years
      treated at the Pediatric Urgency Service Dr. Jaime Chaves in Santa Cruz de
      Tenerife between March 2009 and March 2010. Demographics data, time, presentation
      of complications and referrals to high, triage results according VEUPAP and web_e
      PAT(r), medical discharge and interview results to escort the child report, were
      registered. Sensitivity, specificity, frequency of false positive and negative
      predictive values of results, their concordance with the gold standard, and
      reliability of both methods, were estimated. Results: VEUPAP offers better values
      that web_e-PAT(r) with sensitivity 94% (95% Cl: 91-97%) vs. 36% (95% Cl: 31-41%),
      specificity 93(90-96)% vs. 87(83-91)%, positive predictive value of 89 (86-92)%
      vs. 63(58-68)%, and negative 96(94-98)% vs. 69(64-74)%, yield a4 vs. 3 times
      more, according to expert pediatrician 84(80-88)5 vs. 12(9-15)% reliability and
      64(59-69)% vs. 59(54-63)% according to the weighted kappa Cohen (p < 0.001).
      Three levels lower and upper of triage discrepancies do not occur with any of the
      systems, the discrepancy in lower and upper triage at 2 levels do not occur with
      VEUPAP and is 14% and 4% respectively with web_e-PAT(r) (p = 0.032-0.045). Most
      of the discrepancies occur with triage level 1 being for VEUPAP 2-8% and 10-36%
      for web_e-PAT(r) (p < 0.001). The time consumption for both systems reached
      significance only for priority level 3: 4 (2-7) vs. 4 minutes (2-14),
      respectively (p = 0.044). Conclusions: VEUPAP is a homogeneous and systematic
      objective tool. The characteristics of accuracy, validity, accuracy, reliability,
      usefulness and ease of use make it suitable to assessment and classification
      pediatric patients in primary care emergency.

PMID- 30277369
TI  - [Evaluation of the BD Phoenix ID Yeast System for the Species Identification of
      Clinical Yeast-Like Organisms].
AB  - Most fungi isolated from patients with deep-seated mycosis are yeast-like
      organisms such as Candida and Cryptococcus. As their respective susceptibilities
      to antifungal agents can vary depending on the species, rapid identification is
      important for the administration of appropriate antifungal therapy. The aim of
      this study was to evaluate the performance of a new automated identification
      panel, Phoenix Yeast ID (Becton, Dickinson Diagnostics, USA) as well as the time
      required for identification. The identification results of 106 isolates generated
      by this system were then compared with those of the API 20C AUX system (SYSMEX
      bioMerieux Co., Ltd. Japan). Among the 106 isolates, the identification agreement
      between the two yeast panels was 97/106 (91.5%). Of the 9 (8.5%) discrepant
      identifications, 5 identification using the Phoenix Yeast ID system and 1
      identification using the API 20C AUX system agreed with the genotypic
      identification. Genotypic identification did not agree with the Phoenix Yeast ID
      or API 20C AUX findings for the remaining 3 discrepant
      identifications.Approximately 60% of the C. albicans, C. tropicalis, and C.
      parapsilosis isolates were identified within 4 hours. In total, about 90% of the
      4 major Candida sp. (C. albicans, C. tropicalis and C. glabrata) were identified
      within 8 hours. In conclusion, the Phoenix Yeast ID findings agreed well with the
      API 20C AUX findings. Genotypic identification of the discrepant identifications
      confirmed most of the Phoenix Yeast ID panel identifications. As approximately
      80% of the major Candida sp. could be identified within 8 hours using the Phoenix
      Yeast ID identification system, our results suggest that this system is a
      clinically useful addition to commercially available yeast identification panels.
      The Phoenix Yeast ID system showed excellent concordance with genotypic
      identification for the classification of organisms with discrepant API 20C AUX
      findings.

PMID- 30277370
TI  - [Influence of Stx2 Subtype on Bacteriological Identification of Outbreaks of EHEC
      O157: H- Infections in Saitama City].
AB  - In 2013, two outbreaks of enterohemorrhagic Escherichia coli (EHEC) occurred in
      Saitama city. According to reports from each of the medical institutions that
      detected the EHEC isolates, the isolates seemed to differ in their production of
      Vero Toxin (VT / Shiga Toxin: Stx) since one isolate produced only Stx1 and the
      other produced both Stx1 and Stx2. However, a patient survey conducted by a
      public health center revealed that common foodstuffs had been consumed in both
      outbreaks. Because, the two EHEC isolates were newly detected from two people in
      one patient's family, we analyzed the phenotypic and genetic relationships among
      four isolates in total. All the isolates were serotyped as O157: H-, and both
      stx1 and stx2 were detected. Subsequently, all four isolates were shown to have
      the same pulsed-field gel electrophoresis (PFGE) banding pattern. The findings
      suggested that these isolates belonged to the same strain group. Among these
      cases, the isolates had stx2c which is one of the stx2 subtypes. Reportedly, some
      cases with the Stx2 subtype can not be detected using conventional tests for
      toxin. In addition, Stx2 can be overlooked as a result of this limitation of Stx
      production tests. Both epidemiological research by public health centers and
      genetic analysis by prefectural and municipal public health institutes (PHIs) are
      very important for clarifying possible relationships among outbreaks, as in the
      present cases. Moreover, collaborations and networks among medical institutions,
      PHIs and public health centers should be further strengthened to prevent the
      spread of infections.

PMID- 30277371
TI  - [Syphilis Testing and High Rate of Infection Among HIV-infected Patients].
AB  - Background: The incidence of syphilis has globally increased over the last
      decade, particularly among men who have sex with men coinfected with the human
      immunodeficiency virus (HIV). HIV infection may make the clinical symptoms and
      seroreactivity of syphilis atypical, which requires careful consideration in
      terms of diagnoses and treatments by clinicians. Syphilis is known as a great
      imitator, and is often difficult to be diagnosed or it can be overlooked if
      clinicians depend only on its symptoms or signs. It is also highly contagious and
      could be transmitted without sexual intercourse, and reinfection is common.
      Guidelines recommend that all HIV-infected persons be provided with STD
      screening, including syphilis, at least annually. However, to our knowledge,
      there are no published data on the actual frequency of testing and instances of
      syphilis among HIV-infected persons in Japan. Materials and Methods: We collected
      data from HIV infected male patients who had sex with men (MSM) at Tokyo Medical
      University Hospital from June 2011 to June 2012. Data from the patients, who had
      been tested with the rapid plasma reagin assay (RPR) at least once during the
      study period, were retrospectively obtained from clinical records and were
      analyzed. Results: Among 1000 patients with HIV infection, 935 patients were MSM.
      723 patients (77.4%) were tested using the Treponema pallidum latex agglutination
      test (TPLA) and RPR more than once during the study period. Out of the 723
      patients, 443 patients (61.3%) were reactive for TPLA and 238 patients (32.9%)
      had reactive tests for RPR. All patients who were reactive for RPR were reactive
      for TPLA. Among the patients who were reactive for RPR, 93 patients (12.9%) were
      considered newly diagnosed or with a repeat infection. In this cohort, all
      patients were MSM with a median age of 37 years, and a median CD4+T-lymphocyte
      cell count of 465/uL. A total of 76 patients had been prescribed antiretroviral
      therapy, and 61 patients had a documented HIV-1 RNA viral load of <40 copies/mL
      at their most recent test. Two patients both developed two episodes of syphilis
      during the study period. Of the 95 episodes, 44% were symptomatic syphilis and
      the most common symptom among them was a skin rash at the second stage. Nearly
      half of the patients (47%) were diagnosed at regular screenings. Two thirds (67%)
      had syphilis infections before the study period, whereas at least 20% of them
      were newly diagnosed during the study period. Conclusions: A substantial
      percentage of the participants were newly or recurrently diagnosed with syphilis
      during the study period. More public health awareness should be encouraged
      regarding the current epidemic of syphilis among HIV-infected persons in Japan.
      It is also important for clinicians to provide HIV-infected persons with
      periodical syphilis screening, regardless of the apparent clinical signs or
      symptoms to achieve earlier treatment intervention.

PMID- 30277372
TI  - [Impact of Infection Prevention Program Central Venous Catheter in Intensive Care
      Units].
AB  - Introduction: The channeling of central venous catheters (CVC) is a technique
      used in intensive care units (ICUs) but it doesn't come without the risk of
      infection in the placement and subsequent handling. Objective: Evaluate the
      effectiveness of a prevention of infection following the introduction of new
      multifactorial strategies in the prevention program Central line-associated
      bloodstream infection (CLABSI) at ICU. Methodology: Comparative descriptive study
      in two periods, including all patients admitted in multipurpose ICUs of a
      tertiary hospital 2014. We analyzed 2014 data compared with 2013, to test the
      impact of new measures CRB prevention program. Variables: number of catheters,
      number of infections/1000 catheter days and path. Actions carried out were:
      prospective surveillance of the incidence rate, sequential program multifactorial
      prevention implementation of different measures, checklist for insertion of new
      catheters, introduction of weekly monitoring compliance, reporting episodes team
      are, continuing education for sanitary personal and implementation of the
      semipermeable transparent dressings with chlorhexidine gel. Results: The overall
      incidence density rate decreased from 3.1 episodes/1000 catheter days in 2013 to
      2.3 episodes/1000 catheter days in 2014, improving in different units. The
      utilization ratio of the different accesses was: 35% humeral; 33% jugular; 25%
      subclavian; 10% femoral, and 13% hemodialysis catheter. Conclusions: The new
      measures applied to reduce the bacteremia have allowed a decrease in the rate of
      infection, what brings closer to the objective of the Bacteremia Zero program.

PMID- 30277373
TI  - [A Case Diagnosed as Iatrogenic Vesical Tuberculosis 4 Years after Intravesical
      Immunotherapy Using Bacillus Calmette-Guerin (BCG) for the Treatment of Bladder
      Carcinoma].
AB  - We report a case of iatrogenic vesical tuberculosis diagnosed 4 years after
      intravesical immunotherapy using Bacillus Calmette- Guerin (BCG) for the
      treatment of bladder carcinoma.A 72-year-old man underwent a transurethral
      resection (TUR) of multiple noninvasive urothelial carcinomas and intravesical
      BCG infusion (40 mg/week) for 7 weeks to prevent the recurrence of bladder
      carcinoma. BCG infusion therapy was terminated because of the appearance of
      Reiter's syndrome, including arthritis of the left toe joint, conjunctivitis and
      non-gonococcal urethritis as complications. The patient suffered from repeated
      cystitis, bladder atrophy and urethral stenosis.The cystitis improved with the
      administration of antibiotics (Levofloxacin) but persisted without a complete
      cure. Four years later, a cystoscopy revealed mucosal erosion and a white
      coating. An acid-fast bacteria examination of a urine sample using bacteria
      incubation and DNA PCR revealed the presence of Mycobacterium bovis. Finally,
      anti-tuberculosis therapy (INH+REP+EB) was initiated after the patient was
      diagnosed as having iatrogenic bladder tuberculosis resulting from BCG
      immunotherapy. The tuberculosis bacteria subsequently disappeared from the urine
      samples, and the gross appearance of the bladder mucosa improved. Bladder
      carcinoma has not recurred to date.Intravesical BCG infusion therapy has a good
      anti-tumor effect and can help prevent tumor recurrence after TUR therapy in case
      of noninvasive bladder carcinoma. However, there is a risk of severe
      complications arising from the BCG infusion. In the present case, an adequate
      bacteria examination was not performed, even though antibiotics were repeatedly
      administered for cystitis. In particular, the patient was not tested for the
      presence of acid-fast bacteria for 4 years after the intravesical BCG infusion
      therapy. Furthermore, among patients who received anti-bacteria therapy for
      repeated cystitis after BCG infusion, a bacteria examination including bacteria
      incubation, was not ordered in 19 out of 30 cases treated at our hospital over
      the past 5 years. In conclusion, bacteria examination, including tests for acid
      fast bacteria, should be immediately performed when repeated and/or persistent
      cystitis occurs after BCG infusion therapy.

PMID- 30277374
TI  - [Splenic Infarctions Caused by Acute Cytomegalovirus Infection: A Case Report].
AB  - We report a 48-year-old healthy man who presented with a 1-week history of fever
      and epigastric pain. He had traveled to Indonesia and had been in sexual contact
      with a local woman 4 weeks prior to admission. His peripheral blood film showed
      atypical reactive lymphocytes. A serological test for cytomegalovirus IgM was
      positive and the quantitative cytomegalovirus DNA level was 1.1*102 copies/mL,
      whereas Epstein-Barr virus IgM, HIV antigen and antibody tests were negative. He
      was diagnosed as having an acute cytomegalovirus infection and was treated with
      acetaminophen. However, his clinical symptoms deteriorated on the 4th day after
      admission and a computed tomography examination showed splenomegaly with wedge
      shaped splenic infarctions. Blood culture, antinuclear antibodies,
      antineutrophilic cytoplasmic antibodies, anti-cardiolipin antibodies, and lupus
      anticoagulant tests were negative. The protein C and protein S activities were
      normal. He was diagnosed as having a splenic infarction caused by an acute
      cytomegalovirus infection, and intravenous heparin administration was performed.
      On day 12, his symptoms had improved and he was discharged. Splenic infarctions
      caused by acute cytomegalovirus infection can develop in immunocompetent patients
      without any coagulation disorder. The possibility of splenic infarctions should
      be considered in patients with acute cytomegalovirus infection, especially those
      experiencing a worsening of abdominal pain.

PMID- 30277376
TI  - Impact of Strain-Induced Changes in Defect Chemistry on Catalytic Activity of
      Nd2NiO4+delta Electrodes.
AB  - It is well known that defect chemistry plays a vital role in determining the
      electronic structure, ionic conductivity, and catalytic activity of metal oxides,
      as demonstrated in perovskite-based oxides to achieve desired functionalities. In
      this work, we explored the possibility of tuning the defect chemistry and
      hydrogen oxidation reaction (HOR) activity of Nd2NiO4+delta model thin films by
      controlling the lattice strain. Highly textured Nd2NiO4+delta thin films with
      different strain states were prepared on (110)- and (100)-oriented single-crystal
      yttrium-stabilized zirconium (YSZ) substrates using pulsed laser deposition.
      Electrochemical impedance spectroscopy results indicated that the NNO(100) film
      on the YSZ(110) substrate with larger tensile strain in the a- b plane and
      compressive strain along the c axis exhibited higher HOR activity than the
      NNO(110) film on the YSZ(100) substrate at 500-600  degrees C. The enhancement in
      HOR activity is attributed to the strain-induced difference in the oxygen defect
      concentration, as confirmed by high-resolution X-ray diffraction analysis. We
      believe that the correlation among the strain state, defect chemistry, and
      catalytic properties is helpful for rational design of more efficient electrode
      materials.

PMID- 30277375
TI  - Construction of a High-Efficiency Drug and Gene Co-Delivery System for Cancer
      Therapy from a pH-Sensitive Supramolecular Inclusion between Oligoethylenimine-
      graft-beta-cyclodextrin and Hyperbranched Polyglycerol Derivative.
AB  - Introducing genes into drug-delivery system for a combined therapy has become a
      promising strategy for cancer treatment. However, improving the in vivo therapy
      effect resulted from the high delivery efficiency, low toxicity, and good
      stability in the blood remains a challenge. For this purpose, the supramolecular
      inclusion was considered to construct a high-efficiency drug and gene co-delivery
      system in this work. The oligoethylenimine-conjugated beta-cyclodextrin (beta-CD
      PEI600) and benzimidazole-modified four-arm-polycaprolactone-initiated
      hyperbranched polyglycerol (PCL-HPG-BM) were synthesized as the host and guest
      molecules, respectively, and then the co-delivery carrier of PCL-HPG-PEI600 was
      formed from the pH-mediated inclusion interaction between beta-CD and BM. PCL-HPG
      PEI600 showed the improved drug (doxorubicin, DOX) and gene (MMP-9 shRNA plasmid,
      pMMP-9) delivery ability in vivo, and their cellular uptake and intracellular
      delivery were investigated. Particularly, PCL-HPG-PEI600 showed excellent pMMP-9
      delivery ability with significantly higher transfection efficiency than PEI25k
      due to its excellent serum resistance. For the combined therapy to breast cancer
      MCF-7 tumor, the co-delivery system of PCL-HPG-PEI600/DOX/pMMP-9 resulted in a
      much better inhibition effect on MCF-7 cell proliferation and migration in vitro
      as well as the suppression effect on MCF-7 tumors in vivo compared to those of
      single DOX or pMMP-9 formulation used. Moreover, PCL-HPG-PEI600 displayed
      nontoxicity and excellent blood compatibility, suggesting a promising drug and
      gene co-delivery carrier in combined therapy to tumors.

PMID- 30277377
TI  - A New Type of Three-Dimensional Hybrid Polymeric Haloplumbate Based on Rare High
      Nuclear Heterometallic Clusters.
AB  - A series of new three-dimensional hybrid heterometallic haloplumbates [Pb8M(MU3
      O)2X8(XH)(eg)3] n {H2eg = ethylene glycol; X = Cl, M = Co (1a), Ni (1b), Zn (1c);
      X = Br, M = Ni (2a), Zn (2b); X = I, M = Zn (3)} have been solvothermally
      synthesized and structurally characterized. Compounds 1a-c, 2a-b, and 3 consist
      of one-dimensional haloplumbate [Pb2X9] chains, and heptanuclear heterometallic
      [Pb6M(MU3-O)2(eg)3] clusters based on two [Pb3(MU3-O)(eg)1.5] cores share one M2+
      ion, which are interconnected to generate three-dimensional heterometallic
      frameworks. Although a few heterometallic haloplumbates incorporating other metal
      complexes have been reported, they usually exhibit low-dimensional structures.
      The present heterometallic haloplumbates offer good examples of applying high
      nuclear heterometallic [Pb6MO2(eg)3] clusters to construct a new type of high
      dimensional hybrid heterometallic haloplumbate. Compounds 1a-b and 2a indicate
      unusual ferrimagnetic behavior. Their optical properties are investigated at room
      temperature, and density functional theory calculations of compounds 1c, 2b, and
      3 are also studied.

PMID- 30277378
TI  - Injection-Molded Microfluidic Device for SERS Sensing Using Embedded Au-Capped
      Polymer Nanocones.
AB  - To enable affordable detection and diagnostic, there is a need for low-cost and
      mass producible miniaturized sensing platforms. We present a fully polymeric
      microfluidic lab-on-a-chip device with integrated gold (Au)-capped nanocones for
      sensing applications based on surface-enhanced Raman spectroscopy (SERS). All
      base components of the device were fabricated via injection molding (IM) and can
      be easily integrated using ultrasonic welding. The SERS sensor array, embedded in
      the bottom of a fluidic channel, was created by evaporating Au onto IM nanocone
      structures, resulting in densely packed Au-capped SERS active nanostructures.
      Using a Raman active model analyte, trans-1,2-bis-(4-pyridyl)-ethylene, we found
      a surface-averaged SERS enhancement factor of ~5 * 106 with a relative standard
      deviation of 14% over the sensor area (2 * 2 mm2), and a 18% signal variation
      among substrates. This reproducible fabrication method is cost-effective, less
      time consuming, and allows mass production of fully integrated polymeric,
      microfluidic systems with embedded high-density and high-aspect ratio SERS
      sensor.

PMID- 30277379
TI  - Restriction Enzyme Analysis of Double-Stranded DNA on Pristine Single-Walled
      Carbon Nanotubes.
AB  - Nanoprobes such as single-walled carbon nanotubes (SWCNTs) are capable of label
      free detection that benefits from intrinsic and photostable near-infrared
      fluorescence. Despite the growing number of SWCNT-based applications, uncertainty
      surrounding the nature of double-stranded DNA (dsDNA) immobilization on pristine
      SWCNTs has limited their use as optical sensors for probing DNA-protein
      interactions. To address this limitation, we study enzyme activity on unmodified
      dsDNA strands immobilized on pristine SWCNTs. Restriction enzyme activity on
      various dsDNA sequences was used to verify the retention of the dsDNA's native
      conformation on the nanotube surface and to quantitatively compare the degree of
      dsDNA accessibility. We report a 2.8-fold enhancement in initial enzyme activity
      in the presence of surfactants. Forster resonance electron transfer (FRET)
      analysis attributes this enhancement to increased dsDNA displacement from the
      SWCNT surface. Furthermore, the accessibility of native dsDNA was found to vary
      with DNA configuration and the spacing between the restriction site and the
      nanotube surface, with a minimum spacing of four base pairs (bp) from the
      anchoring site needed to preserve enzyme activity. Molecular dynamics (MD)
      simulations verify that the anchored dsDNA remains within the vicinity of the
      SWCNT, revealing an unprecedented bimodal displacement of the bp nearest to SWCNT
      surface. Together, these findings illustrate the successful immobilization of
      native dsDNA on pristine SWCNTs, offering a new near-infrared platform for
      exploring vital DNA processes.

PMID- 30277380
TI  - Affinity-Modulated Molecular Beacons on MoS2 Nanosheets for MicroRNA Detection.
AB  - DNA-functionalized layered two-dimensional transition-metal dichalcogenides have
      attracted tremendous interest for constructing biosensors in recent years. In
      this work, we report diblock molecular beacons with poly-cytosine (polyC) tails
      anchored on molybdenum disulfide (MoS2) nanosheets as probes for microRNA
      detection. The polyC block is adsorbed on MoS2 and the molecular beacon block is
      available for hybridization to the target; duplex-specific nuclease provides
      signal amplification by target recycling. By changing the length of polyC, we
      regulate the density of probes on MoS2 and inhibit the adsorption of enzyme
      cleaved oligonucleotides, thereby leading to higher quenching efficiency. PolyC
      mediated molecular beacons on MoS2 have very low background signal, ultrahigh
      sensitivity (limit of detection ~3.4 fM), specificity to detect a single
      nucleotide mismatch, and selectivity to detect target microRNA from serum
      samples. This detection platform holds great potential for quantitative analysis
      of miRNAs in clinical diagnosis and biomedical research.

PMID- 30277381
TI  - Slow Magnetic Relaxation in Cobalt(II) Field-Induced Single-Ion Magnets with
      Positive Large Anisotropy.
AB  - Three pentacoordinate complexes of the type [Co( pypz)X2], where pypz is a
      tridentate ligand 2,6-bis(pyrazol-1-yl)pyridine and X = Cl- (1), NCS- (2), and
      NCO- (3), have been synthesized, and their structures have been determined by X
      ray analysis. The DC magnetic data show a sizable magnetic anisotropy, which was
      confirmed by high-field high-frequency electron paramagnetic resonance (HF EPR)
      measurements. Well-resolved HF EPR spectra of high spin cobalt (II) were observed
      over the microwave frequency range 100-650 GHz. The experimental spectra of both
      complexes were simulated with axial g tensor components, a very large positive D
      value, and different E/ D ratios. To determine the exact D value for 2 (38.4 cm
      1) and 3 (40.92 cm-1), the far-infrared magnetic spectroscopy method was used.
      Knowledge of the zero field splitting parameters and their signs is crucial in
      interpreting the single-molecule magnet or single chain magnet behavior. The AC
      susceptibility data confirm that these complexes exhibit a slow magnetic
      relaxation under small applied DC field with two (1 and 3) or three (2)
      relaxation modes.

PMID- 30277382
TI  - Rhombohedral Lanthanum Manganite: A New Class of Dirac Half-Metal with Promising
      Potential in Spintronics.
AB  - Dirac half-metals have drawn great scientific interests in spintronics because of
      their outstanding physical properties such as the large spin polarization and
      massless Dirac fermions. By using first-principles calculations, we investigate
      the perovskite-type lanthanum manganite (LaMnO3) as a novel Dirac half-metal.
      Specifically, LaMnO3 displays multiple linear band crossings in the spin-up
      direction, while it has a large band gap (~5 eV) in the spin-down orientation.
      The intriguing linear band dispersions guarantee the ultrafast electron transport
      and the significant band differences between spin up and down directions promise
      the realization of 100% spin-polarized current and the extremely low energy
      consumption. Such a spin-polarized Dirac material is rare among perovskite-type
      compounds. By adopting the mean-field theory, the estimated Curie temperature Tc
      is 438.4 K. Importantly, the LaMnO3 crystal has been experimentally realized 2
      decades ago, which facilitates the future experimental validation. With the novel
      spin-polarized electronic properties and the high possibility of experimental
      fabrication, LaMnO3 is ideal for the spintronic application.

PMID- 30277383
TI  - Mesoporous Metal Oxide Encapsulated Gold Nanocatalysts: Enhanced Activity for
      Catalyst Application to Solvent-Free Aerobic Oxidation of Hydrocarbons.
AB  - Here, we present a series of experimental studies to encapsulate ultrasmall gold
      nanoparticles into mesoporous metal oxide via an in situ self-assembly method.
      Notably, the 2.0Au@mZnO catalyst (~2.0 nm gold nanoparticles loading on
      mesoporous ZnO nanospheres) shows excellent catalytic activity for indane
      oxidation (120  degrees C, conversion 88.5%) and affords much high turnover
      frequencies (9521 h-1). The catalytic activity of these gold-based catalysts was
      found to be correlated with the size of gold nanoparticles and the types of metal
      oxide supports. With a decrease in gold nanoparticle size, the catalytic
      conversion efficiency of indane oxidation increased. In addition, such catalysts
      possessed high thermal and chemical stability and could be reused more than 10
      times without a remarkable loss of catalytic activity.

PMID- 30277384
TI  - Design of Robust Thermal and Anion Dual-Responsive Membranes with Switchable
      Response Temperature.
AB  - In this study, poly(ionic liquids/ N-isopropylacrylamide) (PIL/NIPAM) modified
      poly(ether sulfone) microporous membranes were prepared using a pore-filling
      method. Due to the anion-sensitive wettability of the PIL and the thermal
      sensitive phase transformation of PNIPAM, the permeability of the modified
      membranes showed robust anion and thermal dual-responsive behaviors. In addition,
      the response temperature of the membranes could be adjusted precisely from 30 to
      55  degrees C by anion exchange, which was attributed to the cooperative
      interaction of the PIL and PNIPAM. The switchable response temperature and the
      dual-responsive performances of the membranes were demonstrated by measuring the
      water fluxes under various conditions. The results indicated that the membrane
      permeabilities increased when exchanging the counteranions (CAs) from hydrophilic
      to hydrophobic ones; the thermal response behaviors were also obvious, and the
      sensitivity increased when increasing the hydrophobicity of the CA (the fluxes
      could be adjusted from 0 to 3800 mL/m2 mmHgh by controlling the temperature and
      CAs). At last, filtration tests were designed with the membranes, and the results
      indicated that by controlling the temperature and/or CA species, three different
      poly(ethylene glycol) molecules could be easily separated according to their
      molecule sizes in a single step.

PMID- 30277385
TI  - Fluorinated Prolines as Conformational Tools and Reporters for Peptide and
      Protein Chemistry.
AB  - Amide bonds at the proline nitrogen are particularly susceptible to rotation,
      affording cis and trans isomers. Installation of a stereochemically defined
      electron-withdrawing fluorine atom or fluorinated groups has the power to
      influence the cis- trans conformational preferences of the amide bond in X-(F)Pro
      (where X = any other amino acid). Advantageously, this also provides a sensitive
      reporter for 19F nuclear magnetic resonance (NMR) studies of protein
      conformation, interactions, and dynamics. We deliberately use the term
      "fluorinated prolines" as an all-encompassing term to describe proline analogues
      containing one or more fluorine atoms and to avoid confusion with the more well
      known 4-fluoroprolines. This review presents a critical discussion of the growing
      repertoire of fluorinated prolines that have been described and, importantly,
      provides a comparison of their uses and relative influence on amide-bond
      conformation and discusses the significant potential of using 19F NMR as a tool
      to probe conformational changes in polypeptides.

PMID- 30277386
TI  - Silica-Encapsulated DNA-Based Tracers for Aquifer Characterization.
AB  - Environmental tracing is a direct way to characterize aquifers, evaluate the
      solute transfer parameter in underground reservoirs, and track contamination. By
      performing multitracer tests, and translating the tracer breakthrough times into
      tomographic maps, key parameters such as a reservoir's effective porosity and
      permeability field may be obtained. DNA, with its modular design, allows the
      generation of a virtually unlimited number of distinguishable tracers. To
      overcome the insufficient DNA stability due to microbial activity, heat, and
      chemical stress, we present a method to encapsulated DNA into silica with control
      over the particle size. The reliability of DNA quantification is improved by the
      sample preservation with NaN3 and particle redispersion strategies. In both sand
      column and unconsolidated aquifer experiments, DNA-based particle tracers
      exhibited slightly earlier and sharper breakthrough than the traditional solute
      tracer uranine. The reason behind this observation is the size exclusion effect,
      whereby larger tracer particles are excluded from small pores, and are therefore
      transported with higher average velocity, which is pore size-dependent. Identical
      surface properties, and thus flow behavior, makes the new material an attractive
      tracer to characterize sandy groundwater reservoirs or to track multiple sources
      of contaminants with high spatial resolution.

PMID- 30277387
TI  - Copper Sulfide-Based Plasmonic Photothermal Membrane for High-Efficiency Solar
      Vapor Generation.
AB  - Solar vapor generation has attracted tremendous attention as one of the most
      efficient ways of utilizing solar energy. It is highly desirable to develop low
      cost, eco-friendly, and high-efficiency solar absorbers for practical
      applications of solar vapor generation. Herein, a three-dimensional plasmonic
      covellite CuS hierarchical nanostructure has been synthesized as the light
      absorbing material via a facile one-pot hydrothermal method for structurally
      integrated solar absorbers with microporous poly(vinylidene fluoride) membrane
      (PVDFM) as the supporting material. A broadband and highly efficient light
      absorption has been achieved in the wavelength of 300-2500 nm, along with high
      water evaporation efficiencies of 90.4 +/- 1.1 and 93.3 +/- 2.0% under 1 and 4
      sun irradiation, respectively. Meanwhile, stable performance has been
      demonstrated for over 20 consecutive runs without much performance degradation.
      To the best of our knowledge, this is the highest performance among the copper
      sulfide-based solar absorbers. With the additional features of low-cost and
      convenient fabrication, this plasmonic solar absorber exhibits a tremendous
      potential for practical solar vapor generation.

PMID- 30277388
TI  - Control of Size and Composition of Colloidal Nanocrystals of Manganese Oxide.
AB  - A comprehensive study on the effects of experimental parameters on the
      composition and size of manganese oxide nanocrystals was completed using
      colloidal chemistry. The reactions studied involved the thermolysis of Mn2+
      acetate and Mn3+ acetylacetonate in oleylamine. Temperature was found to be the
      dominant factor affecting the composition and size of the products. Reactions
      completed below 200  degrees C favored the formation of nanocrystals smaller than
      20 nm, with the presence of even impurity amounts of oxidizing agents leading to
      the formation of Mn3O4. Nanocrystals of MnO could only be synthesized below 200 
      degrees C if Mn2+ acetate was used, and the reaction was carefully controlled to
      have no O2 and H2O contamination. In turn, particle growth was rapid above this
      temperature. In this case, regardless of the oxidizing agents used or oxidation
      state of the Mn precursor, nanocrystals of MnO formed after annealing for at
      least 1 h at temperatures higher than 200  degrees C. This finding suggests the
      role of oleylamine as solvent, surfactant, and reducing agent at sufficiently
      high annealing temperatures. These results increase the understanding of redox
      stability of manganese during the colloidal synthesis of semiconductor metal
      oxide nanocrystals.

PMID- 30277389
TI  - Graphene Oxide Membranes with Conical Nanochannels for Ultrafast Water Transport.
AB  - Membrane-based separations have been increasingly utilized to address global
      energy crisis and water scarcity. However, the separation efficiency often
      suffers from the trade-off between membrane permeability and selectivity.
      Although great efforts have been devoted, a membrane with both high permeability
      and high selectivity remains a distant prospect. Inspired by the hourglass
      structure and ultrafast water transport in aquaporins, we propose a novel
      approach to fabricating membranes with conical nanochannels to reduce the mass
      transfer resistance and to introduce Laplace pressure as the internal driving
      force, which successfully breaks the permeability/selectivity trade-off. First,
      sulfonated polyaniline (SPANI) nanorods were in situ-synthesized and vertically
      aligned on sulfonated graphene oxide (SGO) nanosheets, forming SGO-SPANI X
      composites. Then, the graphene oxide (GO) membranes were fabricated by assembling
      SGO-SPANI X composites through pressure-assisted filtration, in which the SPANI
      nanorods would bend and flatten on the SGO nanosheets under low shear force,
      forming stripe arrays on SGO nanosheets. The tilted stripe arrays between the
      adjacent SGO nanosheets form the conical nanochannels inside GO membranes. The
      conical nanochannels significantly decreased the steric hindrance and enabled the
      generation of Laplace pressure as the internal driving force within membranes.
      Consequently, the resulting membranes exhibit an ultrahigh water permeability of
      1222.77 L.m-2.h-1.bar-1 and high efficiency in dye removal from water with a
      rejection of 90.44% and permeability of 528 L.m-2.h-1.bar-1.

PMID- 30277390
TI  - Temperature-Dependent Nuclear Spin Relaxation Due to Paramagnetic Dopants Below
      30 K: Relevance to DNP-Enhanced Magnetic Resonance Imaging.
AB  - Dynamic nuclear polarization (DNP) can increase nuclear magnetic resonance (NMR)
      signal strengths by factors of 100 or more at low temperatures. In magnetic
      resonance imaging (MRI), signal enhancements from DNP potentially lead to
      enhancements in image resolution. However, the paramagnetic dopants required for
      DNP also reduce nuclear spin relaxation times, producing signal losses that may
      cancel the signal enhancements from DNP. Here we investigate the dependence of 1H
      NMR relaxation times, including T1rho and T2, under conditions of Lee-Goldburg 1H
      1H decoupling and pulsed spin locking, on temperature and dopant concentration in
      frozen solutions that contain the trinitroxide compound DOTOPA. We find that
      relaxation times become longer at temperatures below 10 K, where DOTOPA electron
      spins become strongly polarized at equilibrium in a 9.39 T magnetic field. We
      show that the dependences of relaxation times on temperature and DOTOPA
      concentration can be reproduced qualitatively (although not quantitatively) by
      detailed simulations of magnetic field fluctuations due to flip-flop transitions
      in a system of dipole-coupled electron spin magnetic moments. These results have
      implications for ongoing attempts to reach submicron resolution in inductively
      detected MRI at very low temperatures.

PMID- 30277391
TI  - Protein-Resistant Property of Egg White Ovomucin under Different pHs and Ionic
      Strengths.
AB  - Ovomucin is a mucin-type glycoprotein accounting for 3.5% (w/w) of total egg
      white proteins. The purpose of the study was to explore the potential of ovomucin
      as a protein-resistant material. Using bovine serum albumin (BSA) as a model
      protein, ovomucin decreased the fluorescence intensities of the adsorbed BSA from
      10.90 +/- 2.18 to 0.67 +/- 0.75, indicating its protein-resistant property. To
      understand the underlying mechanism, pure repulsive forces between ovomucin and
      model proteins (e.g., BSA and ovomucin) at various pHs (2.0, 6.0, and 7.2) and
      ionic strengths (0.1, 10, and 150 mM NaCl) were measured using a surface forces
      apparatus. Further studies by using atomic force microscope imaging, zeta
      potential, and dynamic light scattering suggested that the protein-resistant
      property of ovomucin was mainly attributed to strong electrostatic and steric
      repulsions between protein layers. This work has demonstrated that ovomucin has
      antifouling potential with broad applications in the areas of food processing
      industry and biomedical implants.

PMID- 30277392
TI  - Bifunctional Amine-Squaramides as Organocatalysts in Michael/Hemiketalization
      Reactions of beta,gamma-Unsaturated alpha-Ketoesters and alpha,beta-Unsaturated
      Ketones with 4-Hydroxycoumarins.
AB  - The catalytic efficiency of various amine-squaramides was tested in
      Michael/hemiketalization reactions of 4-hydroxycoumarines with two types of
      enones. Tertiary amine-squaramide organocatalysts afforded the best results
      regarding both activity and enantioselectivity when beta,gamma-unsaturated alpha
      ketoesters were used as the Michael acceptors (yields up to 98%,
      enantioselectivities up to 90% ee). On the other hand, the primary amine
      squaramides are the best choice for related reactions of 4-hydroxycoumarins with
      enones. The corresponding pyrano[3,2- c]chromen-5-on products were obtained in
      high enantiomeric purities (up to 96%). The Michael addition of 4-hydroxycoumarin
      to 4-phenylbut-3-en-2-on directly produced chiral anticoagulant drug ( S)
      warfarin in 92% ee when green solvent 2-MeTHF and catalyst ( S, S)-C8 were used.
      Moreover, an enantiomeric catalyst ( R, R)-C8 gave ( R)-warfarin in >99% ee.

PMID- 30277393
TI  - The Effect of Electrostatic Interactions on the Folding Kinetics of a 3-alpha
      Helical Bundle Protein Family.
AB  - The trio of protein segment repeats called spectrins diverges by more than 2
      orders of magnitude in their folding and unfolding rates, despite having very
      similar stabilities and almost coincidental topologies. Experimental studies
      revealed that the mutation of five particular residues dramatically alters the
      kinetic rates in the slow folders, making them similar to the rates of the fast
      folder. This is considered to be an exceptional behavior which seems in principle
      to challenge the current understanding of the protein folding process. In this
      work, we analyze this scenario, using a simplified computational model, combined
      with state-of-the-art kinetic analysis techniques. Our model faithfully separates
      the kinetics of the fast and slow folders and captures the effect of the five
      mutations. We show that the inclusion of electrostatics in the model is necessary
      to explain the experimental findings.

PMID- 30277394
TI  - DNA Solvation Dynamics.
AB  - Experiments have revealed that DNA solvation dynamics is characterized by
      multiple time scales ranging from a few picoseconds to a few hundred nanoseconds
      and in some cases even up to several microseconds. The last part of decay is not
      only slow but can also be described by a power law (PL). The microscopic origin
      of this PL is yet to be clearly established. Here we present a theoretical study
      employing multiple approaches from time dependent statistical mechanics and
      computer simulations. The present study shows that water dynamics may not account
      for the slow PL decay because the longest time scales describing water dynamics
      could be at most of the order of 100 ps. We find that the DNA solvation dynamics
      is complex, due to multiple different contributions to solvation energy. Our
      investigations also show that the primary candidates for this exotic nature of
      solvation dynamics are the response of the counterions and ions of the buffer
      solution. We first employ the well-known Oosawa model of polyelectrolyte solution
      that includes effects of counterion fluctuations to construct a frequency
      dependent dielectric function. We use it in the continuum model of Bagchi,
      Fleming, and Oxtoby (BOF). We find that it fails to explain the slow PL decay of
      DNA solvation dynamics. We then extend the Oosawa model by employing the
      continuous time random walk technique developed by Scher, Montroll and Lax. We
      find that this approach could explain the long time PL decay, in terms of the
      collective response of the counterions. To check the nature of random walk of
      counterions along the phosphate backbone, we carry out atomistic molecular
      dynamics (MD) simulations with a long (38 base pair) DNA. We indeed find frequent
      occurrence of random walk of tagged counterions along the phosphate backbone. We
      next propose a generalized random walk model for counterion hopping on phosphate
      backbone (observed in our MD simulations) and carry out kinetic Monte Carlo
      simulations to show that the nonexponential contribution to solvation dynamics
      can indeed come from dynamics of such ions. We also employ a mode coupling theory
      (MCT) analysis to understand the slow relaxation that can originate from ions in
      solution due to the use of the buffer. Explicit evaluation suggests that buffer
      ion contribution could explain a logarithmic time dependence in the nanosecond
      time scale but not a power law. To further understand the nonexponentiality of
      solvation dynamics at relatively shorter times (less than 100 ps) we carry out
      atomistic MD simulations with explicit water molecules. Log-normal distributions
      of relaxation times of water dynamics inside the grooves may be responsible for
      the initial multiexponential decay of solvation dynamics. We find that the
      observed faster solvation of groove bound probe than that of the intercalated
      probe could arise from the self-motion of the probe.

PMID- 30277395
TI  - Identification and Characterization of DNA Aptamers Specific for Phosphorylation
      Epitopes of Tau Protein.
AB  - Tau proteins are proteins that stabilize microtubules, but their
      hyperphosphorylation can result in the formation of protein aggregates and, over
      time, neurodegeneration. This phenomenon, termed tauopathy, is pathologically
      involved in several neurodegenerative disorders. DNA aptamers are single-stranded
      oligonucleotides capable of specific binding to target molecules. Using tau
      epitopes predisposed for phosphorylation, we identified six distinct aptamers
      that bind to tau at two phosphorylatable epitopes (Thr-231 and Ser-202) and to
      full-length Tau441 proteins with nanomolar affinity. In addition, several of
      these aptamers also inhibit tau phosphorylation (IT4, IT5, IT6) and tau
      oligomerization (IT3, IT4, IT5, IT6). This is the first report to identify tau
      epitope-specific aptamers. Such tau aptamers can be used to detect tau in
      biofluids and uncover the mechanism of tauopathy. They can be further developed
      into novel therapeutic agents in mitigating tauopathy-associated
      neurodegenerative disorders.

PMID- 30277396
TI  - Atomic-Level Description of Protein Folding inside the GroEL Cavity.
AB  - Chaperonins (ubiquitous facilitators of protein folding) sequester misfolded
      proteins within an internal cavity, thus preventing protein aggregation during
      the process of refolding. GroEL, a tetradecameric bacterial chaperonin, is one of
      the most studied chaperonins, but the role of the internal cavity in the
      refolding process is still unclear. It has been suggested that rather than simply
      isolating proteins while they refold, the GroEL cavity actively promotes protein
      folding. A detailed characterization of the folding dynamics and thermodynamics
      of protein substrates encapsulated within the cavity, however, has been difficult
      to obtain by experimental means, due to the system's complexity and the many
      steps in the folding cycle. Here, we examine the influence of the GroEL cavity on
      protein folding based on the results of unbiased, atomistic molecular dynamics
      simulations. We first verified that the computational setup, which uses a
      recently developed state-of-the-art force field that more accurately reproduces
      the aggregation propensity of unfolded states, could recapitulate the essential
      structural dynamics of GroEL. In these simulations, the GroEL tetradecamer was
      highly dynamic, transitioning among states corresponding to most of the
      structures that have been observed experimentally. We then simulated a small,
      unfolded protein both in the GroEL cavity and in bulk solution and compared the
      protein's folding process within these two environments. Inside the GroEL cavity,
      the unfolded protein interacted strongly with the disordered residues in GroEL's
      C-terminal tails. These interactions stabilized the protein's unfolded states
      relative to its compact states and increased the roughness of its folding free
      energy surface, resulting in slower folding compared to the rate in solution. For
      larger proteins, which are more typical GroEL substrates, we speculate that these
      interactions may allow substrates to more quickly escape kinetic traps associated
      with compact, misfolded states, thereby actively promoting folding.

PMID- 30277397
TI  - Characterization of Bovine Serum Albumin and (-)-Epigallocatechin Gallate/3,4- O
      Dicaffeoylquinic Acid/Tannic Acid Layer by Layer Assembled Microcapsule for
      Protecting Immunoglobulin G in Stomach Digestion and Release in Small Intestinal
      Tract.
AB  - The protein-polyphenol layer by layer (LbL) assembled polymer composite
      microcapsule is a considerable delivery system that can be used to improve the
      bioactive stability and effectiveness of natural compounds in various
      applications. In the present study, three kinds of polyphenols were loaded in the
      sequence of (-)-epigallocatechin gallate (EGCG), 3,4- O-dicaffeoylquinic acid
      (3,4-diCQA), and tannin acid (TA) to prepare a BSA-polyphenol LbL membrane. The
      composition of IgG-(BSA-EGCG/3,4-diCQA/TA) n microcapsules and their stability
      and releasing ability in the gastrointestinal tract were evaluated. In addition,
      by binding of these three kinds of polyphenols to BSA, the thermal denaturation
      temperature and ordered secondary structure of the BSA-polyphenol microcapsules
      were increased, and the time of scavenging activity on 2,2'-azinobis(3
      ethylbenzothiazolin-6-sulfonic acid) free radicals was significantly prolonged.
      These findings suggest that (BSA-EGCG/3,4-diCQA/TA) n microcapsules can not only
      protect IgG in food processing and stomach digestion but also release it in the
      small intestinal tract for bioactive delivery.

PMID- 30277398
TI  - Chemical Synthesis and Application of Biotinylated Oligo-alpha-(1 -> 3)-d
      Glucosides To Study the Antibody and Cytokine Response against the Cell Wall
      alpha-(1 -> 3)-d-Glucan of Aspergillus fumigatus.
AB  - Biotinylated hepta-, nona- and undeca-alpha-(1 -> 3)-d-glucosides representing
      long oligosaccharides of alpha-(1 -> 3)-d-glucan, one of the major components of
      the cell walls of the fungal pathogen Aspergillus fumigatus, were synthesized for
      the first time via a blockwise strategy. Convergent assembly of the alpha-(1 ->
      3)-d-glucan chains was achieved by glycosylation with oligoglucoside derivatives
      bearing 6- O-benzoyl groups. Those groups are capable of remote alpha
      stereocontrolling participation, making them efficient alpha-directing tools even
      in the case of large glycosyl donors. Synthetic biotinylated oligoglucosides (and
      biotinylated derivatives of previously synthesized tri- and penta-alpha-(1 -> 3)
      d-glucosides) loaded on streptavidin microtiter plates were shown to be better
      recognized by anti-alpha-(1 -> 3)-glucan human polyclonal antibodies and to
      induce higher cytokine responses upon stimulation of human peripheral blood
      mononuclear cells than their natural counterpart, alpha-(1 -> 3)-d-glucan,
      immobilized on a conventional microtiter plate. Attachment of the synthetic
      oligosaccharides equipped with a hydrophilic spacer via the streptavidin-biotin
      pair allows better spatial presentation and control of the loading compared to
      the random sorption of natural alpha-(1 -> 3)-glucan. Increase of oligoglucoside
      length results in their better recognition and enhancement of cytokine
      production. Thus, using synthetic alpha-(1 -> 3)-glucan oligosaccharides, we
      developed an assay for the host immune response that is more sensitive than the
      assay based on native alpha-(1 -> 3)-glucan.

PMID- 30277399
TI  - Probing Protein Dynamics Using Multifield Variable Temperature NMR Relaxation and
      Molecular Dynamics Simulation.
AB  - Understanding the interplay between protein function and dynamics is currently
      one of the fundamental challenges of physical biology. Recently, a method using
      variable temperature solid-state nuclear magnetic resonance relaxation
      measurements has been proposed for the simultaneous measurement of 12 different
      activation energies reporting on distinct dynamic modes in the protein GB1. Here,
      we extend this approach to measure relaxation at multiple magnetic field
      strengths, allowing us to better constrain the motional models and to
      simultaneously evaluate the robustness and physical basis of the method. The data
      reveal backbone and side-chain motions, exhibiting low- and high-energy modes
      with temperature coefficients around 5 and 25 kJ.mol-1. The results are compared
      to variable temperature molecular dynamics simulation of the crystal lattice,
      providing further support for the interpretation of the experimental data in
      terms of molecular motion.

PMID- 30277400
TI  - Cubic-Core Hexagonal-Branch Mechanism To Synthesize Bimetallic Branched and
      Faceted Pd-Ru Nanoparticles for Oxygen Evolution Reaction Electrocatalysis.
AB  - A major synthetic challenge is to make metal nanoparticles with nanosized
      branches and well-defined facets for high-performance catalysts. Herein, we
      introduce a mechanism that uses the growth of hexagonal crystal structured
      branches off cubic crystal structured core nanoparticles. We control the growth
      to form Pd-core Ru-branch nanoparticles that have nanosized branches with low
      index Ru facets. We demonstrate that the branched and faceted structural features
      of the Pd-Ru nanoparticles retain high catalytic activity while also achieving
      high stability for the oxygen evolution reaction.

PMID- 30277401
TI  - Phosphine-Catalyzed [3 + 2] Cycloaddition Reaction of alpha-Diazoacetates and
      beta-Trifluoromethyl Enones: A Facile Access to Multisubstituted 4
      (Trifluoromethyl)pyrazolines.
AB  - A novel phosphine-catalyzed [3 + 2] cycloaddition of alpha-diazoacetates and beta
      trifluoromethyl enones has been developed that provides facile access to
      multisubstituted 4-(trifluoromethyl)pyrazolines in good to excellent yields at
      room temperature. In addition, a tandem [3 + 2] cycloaddition/Michael addition is
      also presented.

PMID- 30277402
TI  - Iridium-Catalyzed Asymmetric Hydrogenation of Tetrasubstituted alpha-Fluoro-beta
      enamino Esters: Efficient Access to Chiral alpha-Fluoro-beta-amino Esters with
      Two Adjacent Tertiary Stereocenters.
AB  - An iridium-catalyzed highly efficient asymmetric hydrogenation of challenging
      tetrasubstituted alpha-fluoro-beta-enamino esters was successfully developed
      using bisphosphine-thiourea (ZhaoPhos) as the ligand, which prepared a series of
      chiral alpha-fluoro-beta-amino esters containing two adjacent tertiary
      stereocenters with high yields and excellent
      diastereoselectivities/enantioselectivities (73%-99% yields, >25:1 dr, 91%->99%
      ee, and turnover number (TON) values up to 8600), and no defluorinate byproduct
      was detected.

PMID- 30277403
TI  - Aerobic Catalytic Features in Photoredox- and Copper-Catalyzed Iodolactonization
      Reactions.
AB  - Mechanistic evaluations and comparison of two important aerobic catalytic
      oxidation processes, aerobic copper catalysis and photoredox catalysis, are
      performed. Interesting and distinct catalytic behaviors were observed for a
      common reaction of iodolactonization of alkenoic acids. Namely, the aerobic
      copper catalysis requires the formation of a copper carboxylate, whereas the
      aerobic photoredox catalysis requires the addition of proton sources to proceed
      to completion. Furthermore, the iodolactone products obtained from these
      catalytic processes are extensively derivatized to a number of functionalized
      lactones, including aryl lactones generated from the nickel-catalyzed reductive
      coupling with aryl halides.

PMID- 30277404
TI  - Oxidation Potential Tunable Organic Molecules and Their Catalytic Application to
      Aerobic Dehydrogenation of Tetrahydroquinolines.
AB  - In this work, oxidation potential tunable organic molecules, alkyl 2-phenyl
      hydrazocarboxylates, were disclosed. The exquisite tuning of their oxidation
      potentials facilitated a catalytic dehydrogenation of 1,2,3,4
      tetrahydroquinolines in the presence of Mn(Pc) and O2.

PMID- 30277405
TI  - A Necessary Trade-off for Semiclassical Electrodynamics: Accurate Short-Range
      Coulomb Interactions versus the Enforcement of Causality?
AB  - We investigate two key representative semiclassical approaches for propagating
      resonant energy transfer (RET) between a pair of electronic two-level systems
      (donor and acceptor) with coupled Maxwell-Liouville equations. On the one hand,
      when the electromagnetic (EM) field is treated classically and Coulomb
      interactions are treated quantum-mechanically, we find that a quantum-classical
      mismatch leads to a violation of causality, i.e., the acceptor can be excited
      before the retarded EM field arrives. On the other hand, if we invoke a classical
      intermolecular Coulomb operator, we find that the energy transfer in the near
      field loses quantitative accuracy compared with Forster theory, even though
      causality is strictly obeyed. Thus, our work raises a fundamental paradox when
      choosing a semiclassical electrodynamics algorithm. Namely, which is more
      important: Accurate short-range interactions or long-range causality? Apparently,
      one cannot have one's cake and eat it too.

PMID- 30277406
TI  - An Interrupted Schmidt Reaction: C-C Bond Formation Arising from Nitrilium Ion
      Capture.
AB  - The rerouting of the nitrilium ion formed in the Schmidt reaction of ketones and
      TMSN3 to encompass C-C bond formation with an electron-rich aromatic group is
      reported. Thus, when the reaction is carried out in HFIP using AlCl3 or AlBr3 as
      the promoter, imines, iminium ions, or enamide derivatives are obtained through
      one-pot procedures. The scope and possible mechanisms of these new
      transformations are considered.

PMID- 30277408
TI  - Correction.

PMID- 30277407
TI  - Aortic valvular imaging with cardiovascular magnetic resonance: seeking for
      comprehensiveness.
AB  - Cardiovascular magnetic resonance (CMR) has an emerging role in aortic valve
      disease evaluation (AVD), becoming an all-in-one technique. CMR evaluation of the
      anatomy and flow through the aortic valve has a higher reproducibility than
      echocardiography. Its unique ability of in-vivo myocardial tissue
      characterization, significantly improves the risk stratification and management
      of patients. In addition, CMR is equivalent to cardiac computed tomography
      angiography for trans-aortic valvular implantation and surgical aortic valve
      replacement planning; on the other hand, its role in the evaluation of
      ventricular function improving and post-treatment complications is undisputed.
      This review encompasses the existing literature regarding the role of CMR in AVD,
      exploring all the aspects of the disease, from diagnosis to prognosis.

PMID- 30277409
TI  - The risk for opportunistic infections in inflammatory bowel disease with
      biologics: an update.
AB  - INTRODUCTION: Crohn's disease and Ulcerative Colitis are forms of inflammatory
      bowel disease (IBD), chronic diseases treated with medical and surgical therapy.
      Patients with IBD are treated with potent immunomodulatory agents, leading to
      immunosuppression, and the potential for opportunistic infections. In 2014, the
      ECCO guidelines were released to guide the prevention, diagnosis and treatment of
      a variety of these opportunistic infections. Since 2014, there have been a number
      of new agents released as well as a significant expansion in our knowledge of the
      safety profile of IBD medications. In this paper we review the literature after
      2014 regarding opportunistic infections and updates on safety data. Areas
      covered: We review updates in immunomodulatory therapies for IBD and
      opportunistic infections since the 2014 ECCO guidelines were published. Expert
      commentary: The prevention, diagnosis and treatment of opportunistic infections
      continues to evolve, as new drugs are approved, and the use of a combination of
      biologic agents are considered for therapy in clinical trials. What causes some
      patients to fail to respond to vaccination, or for others to develop severe
      infections, remains unclear. Improved risk stratification for opportunistic
      infections in IBD patients and updated ECCO 2014 guidelines would be of
      significant benefit.

PMID- 30277410
TI  - The Basic Psychological Need Satisfaction and Frustration Scale: Construct and
      Predictive Validity in the Italian Context.
AB  - The Basic Psychological Need Satisfaction and Frustration Scale (BPNSFS) is a
      self-report instrument assessing the satisfaction and frustration of the three
      basic psychological needs of autonomy, competence, and relatedness defined by
      self-determination theory. The aim of this study was to examine the
      dimensionality, the predictive validity, and the measurement invariance across
      different age groups of the Italian version of the BPNSFS. The participants were
      2,204 Italian adolescents and young adults (41% males) from 14 to 28 years old (M
      age = 20.23, SD = 4.25). The invariance across age demonstrated adequate
      equivalence of the 6-factor model of scales across adolescents (14-18 years) and
      young adults (20-24 years), showing general homogeneity with respect to the
      constructs measured in the Italian context. Results of this study suggest that
      the satisfaction and frustration subscales for each need might be treated
      separately, because they might have unique effects that should be explored. For
      this reason, the BPNSFS could be a useful instrument in the counseling context
      because it can be easily used by operators both for assessment and for evaluation
      of the effects and results of counseling intervention.

PMID- 30277411
TI  - Correction.

PMID- 30277412
TI  - Understanding rehabilitation in Ukraine from the perspective of key informants.
AB  - BACKGROUND: The evolution of healthcare in Ukraine has been impacted by a number
      of factors, including years of communist control followed by the birth of an
      emerging democracy and most recently, conflict in the eastern part of the
      country. Rehabilitation is an aspect of Ukraine's healthcare system that is still
      heavily influenced by the Soviet-era mentality of perfectionism. METHODS: This
      article presents the results of a qualitative research study that undertook 13
      key informant interviews to answer the question of what can be learned from the
      perspectives of individuals in Ukraine or with experience working in Ukraine with
      respect to developing and implementing appropriate rehabilitation that is
      inclusive and targets health equity. RESULTS: Key themes that informants
      determined will affect the future of rehabilitation in Ukraine include the
      current health care structure, the culture surrounding disability, international
      and domestic sources of involvement, and a revised curriculum for new and
      existing rehabilitation professionals. CONCLUSIONS: The input from these
      individuals, supported by evidence from the literature, provides a foundational
      understanding of the currently fragmented rehabilitation system in Ukraine and
      the factors that professionals prioritize as integral components of an
      infrastructure that supports rehabilitation in the twenty-first century.
      Implications for Rehabilitation While the recent conflict in Eastern Ukraine has
      served as a lightning rod to shed light on the lack of resources allocated toward
      disability and chronic care in the region, rehabilitation is also lacking in the
      general population, requiring a response that addresses the unique needs of a
      population of over 44 million individuals. Alongside a curriculum that complies
      with international accreditation standards, an influx of job and career
      opportunities developed by the government is needed to encourage individuals to
      work in the rehabilitation sector. A nation-wide strategy must be developed to
      disseminate knowledge about disability and rehabilitation in order to begin to
      address the issues of social exclusion and stigma associated with disability in
      many post-Soviet countries.

PMID- 30277413
TI  - [Recent advances in gout: pathogenesis, diagnosis, comorbidities, treatment].
AB  - After a "silence" period for decades, a great body of new information has become
      available about the pathogenesis, diagnosis and treatment of gout. New data on
      purine metabolism and urate transporters have been published. It has become
      evident that gout is an autoinflammatory disease involving the inflammasome and
      interleukin-1. With respect to diagnosis, microscopic evaluation of the urate
      crystal is still the gold standard, however, sensitive imaging techniques
      (ultrasound, modern computed tomography methods) are able to visualize crystal
      deposition and tophus formation. Tophus size may also be monitored over time. We
      see a renaissance of non-pharmacological, lifestyle-related treatment modalities.
      Pharmacotherapy includes the resolution of attacks and urate-lowering maintenance
      therapy. In 2016, two recent series of recommendations have been published. Treat
      to-target therapy aiming at urate levels <=360 MUmol/l is crucial. Urate-lowering
      therapy includes xanthine oxidase inhibitors (allopurinol, febuxostat). However,
      a number of novel compounds (urate transporter inhibitors, recombinant uricase,
      interleukin-1 inhibitors) are under development or before introduction to gout
      treatment. Comorbidites should be considered throughout the follow-up of gout
      patients. Orv Hetil. 2018; 159(40): 1625-1636.

PMID- 30277414
TI  - [Colorectal cancer susceptibility genetic variants in tumor free and colorectal
      carcinoma bearing Hungarian population. Individual predisposition to cancer].
AB  - Genome-wide association studies (GWAS) using population-based designs have
      identified many genetic loci, at which common variants can influence the risk of
      developing the sporadic colon cancers. These are single nucleotide polymorphisms
      (SNPs) located on different chromosomes, close to genes involved in cancer
      developing process, and the SNPs modify their functions, and as a consequence the
      cancer risk is increased. Our aim was to provide frequency distributions data of
      variable (risk) allele of six independent SNPs in patients with colorectal
      cancers and in control Hungarian population, predicting the increased risk effect
      of sequence variant of SNPs. We also investigated the frequency distribution of
      tumor localization between right or left half of large bowel as well as the RAS
      mutation status. 47 non-tumorous patients and 47 patients with colorectal cancer
      were given oral mucosa cells or blood samples for SNP analysis. After DNA
      isolation, an LC480 (Roche) type PCR instrument, asymmetric LATE PCR method and
      melting point analysis were used for detection of sequence variations, by the
      assistance of two SNP specific primers, unlabeled specific probe and
      intercalating fluorescent dye. Genomic frequency distribution of variable alleles
      of SNPs predisposed to tumor development have been investigated in colorectal
      cancer carrier patients and the results have been compared with the same allele
      frequency distribution data obtained from the non-tumorous control patients and
      from CEU population stored in SNPnexus data base. The homozygous risk alleles of
      SNPs showed a 1.5-2.3-time increase in colorectal cancer carrier patients then in
      control and CEU patients, but the heterozygous risk allele distribution was
      identical in tumorous and control population. The frequency distribution of
      homozygous risk alleles of six SNPs was also investigated in the same time and
      some patients. Among 47 patients with colorectal cancer, in 3 patients carrying 3
      SNPs with homozygous risk alleles, in additional 5 tumor samples two and 24
      samples contain only one SNP's homozygous risk alleles, and in 15 patients, SNPs
      with homozygous risk alleles do not occur. In 47 control patients, only 3 samples
      contain two SNPs with homozygous risk alleles and 17 samples contain only one SNP
      with homozygous risk alleles. Significant differences of the tumorous and the
      control population can be seen detected. NRAS mutation was not found. Our results
      showed a real increased risk effect of several newly recognized low-penetrance
      colorectal cancer susceptibility genetic variants by influence of the regulation
      of neighboring genes, however, the degree of cancer risk is individual, and
      influenced by others environmental factors, such as dietary factors. Orv Hetil.
      2018; 159(40): 1614-1623.

PMID- 30277415
TI  - [Effect of a gel-type denture adhesive on unstimulated whole saliva and minor
      salivary gland flow rates and on subjective orofacial sicca symptoms].
AB  - INTRODUCTION AND AIM: To determine whether the continuous use of gel-type denture
      adhesives influence the unstimulated whole saliva, the palatal and labial saliva
      flow rates, and to assess the possible changes of subjective orofacial sicca
      symptoms. METHOD: 28 maxillary complete denture wearing patients (average age: 70
      +/- 10 years) were investigated. A gel-type denture adhesive was administered to
      the patients for regular use during the 3 weeks of examination. A questionnaire
      of 16 questions was used to evaluate subjective orofacial sicca symptoms.
      Unstimulated whole saliva was determined by the spitting method, palatal and
      labial saliva flow rates were measured by the Periotron(r) device with filter
      paper discs at the initial, first, second and third weeks. STATISTICAL ANALYSIS:
      The following tests were used: subjective values - chi2-test; flow rates - ANOVA,
      paired Student's t-test. RESULTS: According to the questionnaire, the ratio or
      severity of xerostomia did not change. A significant increase in the subjective
      feeling of "saliva thickness" could be detected (p = 0.027), but the other
      subjective parameters remained unchanged. Palatal saliva flow rates decreased
      significantly by week 3 (week 0: 4.21 +/- 3.96 ul/cm2/min; week 3: 2.21 +/- 2.30
      ul/cm2/min; p = 0.024). On the other hand, there was no significant change in the
      unstimulated whole saliva (week 0: 0.37 +/- 0.36 ml/min; week 3: 0.39 +/- 0.35
      ml/min) and labial saliva (week 0: 3.99 +/- 3.75 ul/cm2/min; week 3: 2.58 +/-
      3.39 ul/cm2/min) flow rates. CONCLUSIONS: The regular use of denture adhesives
      did not influence xerostomia and the majority of subjective orofacial sicca
      symptoms, but may cause a subjective feeling of "increased saliva thickness" and
      reduce palatal minor salivary gland flow rates among complete maxillary denture
      wearers. Orv Hetil. 2018; 159(40): 1637-1644.

PMID- 30277417
TI  - [Miscellaneous].

PMID- 30277416
TI  - ["Short" history of the medical faculty of Erzsebet University in Pozsony
      (Bratislava)].

PMID- 30277418
TI  - Hb Hubei [alpha114(GH2)Pro->His, HBA1: c.344C>A]: A Novel Hemoglobin Variant of
      the alpha1-Globin Chain.
AB  - We report here a novel alpha1-globin chain variant, Hb Hubei [alpha114(GH2)Pro
      >His, HBA1: c.344C>A], in a Chinese individual. The proband, a 28-year-old
      Chinese female, was discovered following routine Hb A1c analysis using cation
      exchange high performance liquid chromatography (HPLC). Sanger sequencing
      revealed a novel missense mutation, HBA1: c.344C>A (CCC>CAC), in exon 2 of the
      alpha1-globin gene. The mutation caused a transition of proline to histidine at
      position alpha114(GH2) on the alpha1-globin chain. This new variant was named Hb
      Hubei after the geographic origin of the proband.

PMID- 30277419
TI  - Antiproliferative activity of morpholine-based compounds on MCF-7 breast cancer,
      colon carcinoma C26 and normal fibroblast NIH-3T3 cell lines and study of their
      binding affinity to calfthymus-DNA and bovine serum albumin.
AB  - This report describes the results of a study on the antiproliferative activity of
      the morpholine-based ligand 1,3-bis(1-morpholinothiocarbonyl)benzene (HL) and its
      nickel(II) complex (NiL) against human breast cancer cells (MCF-7), colon
      carcinoma cells (C26) and normal fibroblast NIH-3T3 cells. NiL showed better
      cytotoxicity on both cancerous cells relative to normal cells in vitro with the
      highest selective index of 2.22 in MCF-7 cells. The interaction of both compounds
      with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) was studied using
      various spectroscopic techniques and analytical methods such as UV-vis
      titrations, thermal denaturation, circular dichroism, competitive fluorescent
      intercalator displacement assays, as well as molecular modeling. The fluorescence
      intensity of the probe molecule increases clearly when HL and NiL are added to
      the methylene blue (MB)-DNA system. Furthermore, the binding of HL and NiL
      quenches the BSA fluorescence, revealing a 1:1 interaction with a binding
      constant of about 105 M-1.

PMID- 30277420
TI  - Distinct Effects of Repeated-Sprint Training in Normobaric Hypoxia and beta
      Alanine Supplementation.
AB  - OBJECTIVE: The present study evaluated the effects of repeated-sprint training in
      normobaric hypoxia and beta-alanine supplementation (BA) on aerobic and anaerobic
      performance in recreationally active men. METHODS: Participants were randomly
      assigned to one of the following groups: normoxia/beta-alanine (NB, n = 11),
      normoxia/placebo (NP, n = 8), normobaric hypoxia/beta-alanine (HB, n = 10) and
      normobaric hypoxia/placebo (HP, n = 9). All participants completed 8 training
      sessions over 4 weeks on a cycle ergometer either in normobaric hypoxia (oxygen
      fraction: FiO2 = 14.2%) or normoxia (FiO2 = 20.9%). Participants were instructed
      to consume a daily dosage of 6.4 g of BA or placebo. Changes in performance in a
      graded exercise test, repeated-sprint test (RST), and 3-minute all-out test (3MT)
      were examined before and after training and supplementation. RESULTS: No between
      group differences were observed for training volume or supplementation
      compliance. Anthropometric and hematological measures remained unchanged before
      and after intervention in all groups. A main effect of training condition was
      shown for oxygen consumption and power output at respiratory compensation point,
      average power output during the last sprint of the RST, heart rate recovery
      following the RST, and total work during the 3MT. These measures in the
      normobaric hypoxia groups were significantly (p < 0.05) higher than the normoxia
      groups, except for the heart rate recovery following the RST. A main effect of
      supplement was detected in anaerobic working capacity, with postintervention
      values in the BA groups being significantly (p < 0.05) higher than the placebo
      groups. CONCLUSIONS: Repeated-sprint training in hypoxia improved aerobic
      performance, exercise tolerance, cardiovascular recovery, and overall working
      capacity, while BA maintained the anaerobic working capacity. However, BA did not
      provide additional benefits with respect to attenuating fatigue or enhancing
      repeated-sprint performance.

PMID- 30277422
TI  - Physicochemical properties and in vivo evaluation of Pt/TiO2-SiO2 nanopowders.
AB  - AIM: Sol-gel is a suitable and advantageous method to synthesize mixed oxide
      nanomaterials with unique physicochemical and biological properties. MATERIALS &
      METHODS: In this work, TiO2-SiO2 nanopowders cogeled with platinum
      acetylacetonate were developed and studied in the perspective of nanomedicine.
      The physicochemical properties of the Pt/TiO2-SiO2 nanopowders, named NanoRa2-Pt,
      were evaluated in detail by means of complementary spectroscopic and microscopic
      tools. The nanopowder's biocatalytic efficiency in wound healing was evaluated in
      a Type I diabetes animal model. RESULTS: These are TiO2-SiO2 submicron mesoporous
      particles with variable size and shape containing ultra-small platinum
      nanoparticles with catalytic properties. CONCLUSION: The use of NanoRa2-Pt
      catalyzes the natural healing processes with a faster remodeling stage. These
      sols, which we call nanobiocatalysts, belong to an emerging and very promising
      research field known as catalytic nanomedicine.

PMID- 30277423
TI  - Critical review of renal tubule karyomegaly in non-clinical safety evaluation
      studies and its significance for human risk assessment.
AB  - : Scientific databases were searched for terms applicable to karyomegaly in renal
      tubules of laboratory animals used in preclinical safety evaluation studies, and
      in humans. Renal tubule karyomegaly was more frequently reported in the rat in
      response to chemical exposure compared to other laboratory animal species. Renal
      tubule karyomegaly also occurred in the mouse in response to chemical insult, but
      much less commonly than in the rat. This nuclear lesion was recorded infrequently
      for hamster, dog, guinea pig, rabbit, pig, and non-human primate. Most instances
      of renal karyomegaly reported in humans represented cases of the genetic
      syndrome, karyomegalic interstitial nephritis, known to be caused by a mutation
      in the FAN1 gene. Human reports of karyomegaly in the kidney associated with
      chemical exposure are rare, and linked mainly to chemotherapeutic or antiviral
      therapies. The rat appears to be highly predisposed to developing karyomegaly as
      a renal response on exposure to diverse chemical agents, but karyomegaly in the
      rat is not consistently associated with renal tubule tumor development. Because
      of this inconsistency, renal tubule karyomegaly is an inaccurate predictor of
      renal tubule neoplasia, and there is no evidence that karyomegalic cells are
      involved in tumor development as a form of preneoplasia. A chemically induced
      karyomegalic response in the rat does not necessarily predict a similar
      alteration in human kidneys. Because modest nuclear enlargement of kidney tubule
      cells can occur as physiological or functional responses, it is recommended that
      the threshold for diagnosing renal tubule karyomegaly in animal studies should be
      accepted as at least four times normal nuclear size or larger. ABBREVIATIONS:
      BEN: Balkan Endemic Nephropathy; DMN: dimethylnitrosamine; GLP: Good Laboratory
      Practice; KIN: karyomegalic interstitial nephritis; LAL: lysinoalanine; MeCCNU: 1
      (2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea; NTP: National
      Toxicology Program; OSOM: outer stripe of outer medulla; OTA: ochratoxin A; RTT:
      renal tubule tumor.

PMID- 30277424
TI  - Caregiver Willingness to Treat Atopic Dermatitis is Not Much Improved by
      Anchoring.
AB  - BACKGROUND: Caregivers are often apprehensive about treating their child's atopic
      dermatitis with a topical corticosteroid. Typical concerns include anxiety
      regarding side effects and the perceived burden of treatment. The perception of
      burden may be modifiable through anchoring. OBJECTIVE: To evaluate caregivers'
      willingness to treat their child's atopic dermatitis with a topical
      corticosteroid once-daily if initially anchored to the idea of a four-times-daily
      treatment regimen. METHODS: A prospective survey study was performed in 100
      caregivers of children with atopic dermatitis. Scores were treated as ordinal
      data and evaluated using the Mann-Whitney U test and chi-squared test. RESULTS:
      Of the 100 recruited participants, 97 were eligible and returned completed
      surveys. Subjects anchored to a four-times-daily treatment regimen were more
      willing to treat their child's atopic dermatitis once-daily (mean, 8.7) than
      those not anchored (mean, 7.9), however the difference between these groups was
      not statistically significant (P = 0.173). CONCLUSIONS: Caregivers reported being
      generally quite willing to apply topical corticosteroids once-daily. Anchoring
      was associated with a slightly higher score, though it was not statistically
      significant. For most patients with atopic dermatitis, anchoring may not be
      helpful, but for patients whose main barrier is perceived burdensomeness of
      treatment, anchoring may be of some benefit.

PMID- 30277425
TI  - The long non-coding RNA MALAT1 is increased in renal ischemia-reperfusion injury
      and inhibits hypoxia-induced inflammation.
AB  - BACKGROUND: To investigate the expression of long non-coding RNA metastasis
      associated lung adenocarcinoma transcript 1 (MALAT1) in renal ischemia
      reperfusion injury and explore its role in acute kidney injury. METHODS: 18 mice
      were randomly divided into a sham operation group (Sham) and an ischemia
      reperfusion group (IR) in which animals were sacrificed at 6 h or 12 h after
      surgery. The kidneys were harvested to measure the expression of MALAT1 mRNA. HK2
      cells were treated with cobalt chloride (CoCl2) to mimic hypoxia or transfected
      with siRNA to knockdown MALAT1 before CoCl2 treatment. After that, MALAT1 was
      analyzed by RT-PCR (reverse transcription-polymerase chain reaction). HIF-1alpha
      (hypoxia-inducible factor-1 alpha) and NF-kappaB (nuclear factor-kappa B) was
      measured by Western blot. The concentrations of IL-6 (interleukin-6) and TNF
      alpha (tumor necrosis factor-alpha) in the media were detected by ELISA (enzyme
      linked immunosorbent assay). RESULTS: The expression of MALAT1 in the IR (6 h/12
      h) group was significantly higher than that in the sham group. In HK2 cells,
      MALAT1 was significantly increased at 1 h, 3 h, and 6 h after CoCl2 treatment but
      had reduced to the basal level at 12 h and 24 h. Knockdown of MALAT1 by siRNA
      significantly up-regulated the expression of HIF-1alpha and NF-kappaB proteins in
      CoCl2-treated HK2 cells. In addition, the concentrations of IL-6 and TNF-alpha
      were increased by MALAT1 siRNA transfection in CoCl2-treated HK2 cells.
      CONCLUSION: The expression of MALAT1 is increased in renal ischemia-reperfusion
      injury. It is likely that MALAT1 inhibits the hypoxia-induced inflammatory
      response through the NF-kappaB pathway.

PMID- 30277426
TI  - Serum heme oxygenase 1 (HO-1), soluble FMS like tyrosine kinase (sFlt-1) level,
      and neonatal outcome in early onset, late onset preeclampsia, and normal
      pregnancy.
AB  - OBJECTIVE: To compare the level of serum heme oxygenase 1 (HO-1), soluble FMS
      like tyrosine kinase (sFlt-1), and neonatal outcome in early onset preeclampsia
      (EO-PE), late onset preeclampsia (LO-PE), and normal pregnancy (NP). METHODS: In
      this prospective observational case control study, HO-1 and sFlt-1 levels were
      measured in blood samples within 24 h of hospital admission. Preeclampsia cases
      were divided into two groups based on gestational age at delivery: EO-PE (<34
      weeks) and LO-PE (>=34 weeks). A total of 45 patients were involved in this
      study. RESULT: Maternal serum level of sFlt-1 was higher in EO-PE than LO-PE and
      NP groups (mean +/- SD; 14.50 +/- 17.12 ng/ml vs 5.20 +/- 6.69 ng/ml vs 2.72 +/-
      1.2 ng/ml [p = 0.020]. Maternal serum level of HO-1 was not different between EO
      PE, LO-PE, and NP groups (p = 0.681). Birthweights were significantly lower in
      the EO-PE group compared with the LO-PE and NP groups (1580 +/- 536 g vs 2635 +/-
      578 g vs 3010 +/- 371 g [p = 0.000]). The rate of small for gestational age
      infant (26.7% vs 6.7% vs 0%; p = 0.046) and perinatal death (20% vs 0 vs 0; p =
      0.037) was also significantly higher in EO-PE compared to LO-PE and NP. The
      maternal sFlt-1 level was negatively correlated with birthweight (p = 0.006; CC =
      -0.445). CONCLUSION: This study did not find a correlation between maternal HO-1
      levels and sFlt-1 levels. Maternal serum sFLt-1 levels in preeclampsia were
      higher in EO-PE and were associated with a worse perinatal outcome.

PMID- 30277427
TI  - Prediction of Isocitrate Dehydrogenase Genotype in Brain Gliomas with MRI: Single
      Shell versus Multishell Diffusion Models.
AB  - Purpose The primary aim of this prospective observational study was to assess
      whether diffusion MRI metrics correlate with isocitrate dehydrogenase (IDH)
      status in grade II and III gliomas. A secondary aim was to investigate whether
      multishell acquisitions with advanced models such as neurite orientation
      dispersion and density imaging (NODDI) and diffusion kurtosis imaging offer
      greater diagnostic accuracy than diffusion-tensor imaging (DTI). Materials and
      Methods Diffusion MRI (b = 700 and 2000 sec/mm2) was performed preoperatively in
      192 consecutive participants (113 male and 79 female participants; mean age,
      46.18 years; age range, 14-77 years) with grade II (n = 62), grade III (n = 58),
      or grade IV (n = 72) gliomas. DTI, diffusion kurtosis imaging, and NODDI metrics
      were measured in regions with or without hyperintensity on diffusion MR images
      and compared among groups defined according to IDH genotype, 1p/19q codeletion
      status, and tumor grade by using Mann-Whitney tests. Results In grade II and III
      IDH wild-type gliomas, the maximum fractional anisotropy, kurtosis anisotropy,
      and restriction fraction were significantly higher and the minimum mean
      diffusivity was significantly lower than in IDH-mutant gliomas (P = .011, P =
      .002, P = .044, and P = .027, respectively); areas under the receiver operating
      characteristic curve ranged from 0.72 to 0.76. In IDH wild-type gliomas, no
      difference among grades II, III, and IV was found. In IDH-mutant gliomas, no
      difference between those with and those without 1p/19q loss was found. Conclusion
      Diffusion MRI metrics showed correlation with isocitrate dehydrogenase status in
      grade II and III gliomas. Advanced diffusion MRI models did not add diagnostic
      accuracy, supporting the inclusion of a single-shell diffusion-tensor imaging
      acquisition in brain tumor imaging protocols. Published under a CC BY 4.0
      license. Online supplemental material is available for this article.

PMID- 30277428
TI  - Performance of Hospitalists and Inpatient Clinical Outcomes.
AB  - Use of the hospitalist model has reduced the number of primary care physicians
      taking care of inpatients. Physician shortages in primary care has forced many
      healthcare systems to use locum physicians as part of their delivery system and
      physician practice plan. With value-based purchasing and new payment models,
      measuring quality and patient-satisfaction with the hospitalist model is
      important. Hospital administrators need to carefully monitor the use of locum
      hospitalists, especially around quality of care and clinical outcomes.

PMID- 30277429
TI  - The Neurodynamic Decision Variable in Human Multialternative Perceptual Choice.
AB  - The neural dynamics underpinning binary perceptual decisions and their
      transformation into actions are well studied, but real-world decisions typically
      offer more than two response alternatives. How does decision-related evidence
      accumulation dynamically influence multiple action representations in humans? The
      heightened conservatism required in multiple compared with binary choice
      scenarios suggests a mechanism that compensates for increased uncertainty when
      multiple choices are present by suppressing baseline activity. Here, we tracked
      action representations using corticospinal excitability during four- and two
      choice perceptual decisions and modeled them using a sequential sampling
      framework. We found that the predictions made by leaky competing accumulator
      models to accommodate multiple choices (i.e., reduced baseline activity to
      compensate increased uncertainty) were borne out by dynamic changes in human
      action representations. This suggests a direct and continuous influence of
      interacting evidence accumulators, each favoring a different decision
      alternative, on downstream corticospinal excitability during complex choice.

PMID- 30277430
TI  - The Sources of Dual-task Costs in Multisensory Working Memory Tasks.
AB  - We investigated the sources of dual-task costs arising in multisensory working
      memory (WM) tasks, where stimuli from different modalities have to be
      simultaneously maintained. Performance decrements relative to unimodal single
      task baselines have been attributed to a modality-unspecific central WM store,
      but such costs could also reflect increased demands on central executive
      processes involved in dual-task coordination. To compare these hypotheses, we
      asked participants to maintain two, three, or four visual items. Unimodal trials,
      where only this visual task was performed, and bimodal trials, where a concurrent
      tactile WM task required the additional maintenance of two tactile items, were
      randomly intermixed. We measured the visual and tactile contralateral delay
      activity (CDA/tCDA components) as markers of WM maintenance in visual and
      somatosensory areas. There were reliable dual-task costs, as visual CDA
      components were reduced in size and visual WM accuracy was impaired on bimodal
      relative to unimodal trials. However, these costs did not depend on visual load,
      which caused identical CDA modulations in unimodal and bimodal trials, suggesting
      that memorizing tactile items did not reduce the number of visual items that
      could be maintained. Visual load did not also affect tCDA amplitudes. These
      findings indicate that bimodal dual-task costs do not result from a competition
      between multisensory items for shared storage capacity. Instead, these costs
      reflect generic limitations of executive control mechanisms that coordinate
      multiple cognitive processes in dual tasks. Our results support hierarchical
      models of WM, where distributed maintenance processes with modality-specific
      capacity limitations are controlled by a central executive mechanism.

PMID- 30277431
TI  - Primary Interoceptive Cortex Activity during Simulated Experiences of the Body.
AB  - Studies of the classic exteroceptive sensory systems (e.g., vision, touch)
      consistently demonstrate that vividly imagining a sensory experience of the world
      simulating it-is associated with increased activity in the corresponding primary
      sensory cortex. We hypothesized, analogously, that simulating internal bodily
      sensations would be associated with increased neural activity in primary
      interoceptive cortex. An immersive, language-based mental imagery paradigm was
      used to test this hypothesis (e.g., imagine your heart pounding during a roller
      coaster ride, your face drenched in sweat during a workout). During two
      neuroimaging experiments, participants listened to vividly described situations
      and imagined "being there" in each scenario. In Study 1, we observed
      significantly heightened activity in primary interoceptive cortex (of dorsal
      posterior insula) during imagined experiences involving vivid internal
      sensations. This effect was specific to interoceptive simulation: It was not
      observed during a separate affect focus condition in Study 1 nor during an
      independent Study 2 that did not involve detailed simulation of internal
      sensations (instead involving simulation of other sensory experiences). These
      findings underscore the large-scale predictive architecture of the brain and
      reveal that words can be powerful drivers of bodily experiences.

PMID- 30277432
TI  - 2018 APA Psychiatric Services Achievement Awards.

PMID- 30277433
TI  - Silver Award: Reciprocal Peer Support for Addressing Mental Health Crises Among
      Police, Veterans, Mothers of Special Needs Children, and Others.

PMID- 30277434
TI  - Gold Award: 24/7 Wraparound Services That Help Persons With Serious Mental
      Illnesses to Live in the Community.

PMID- 30277435
TI  - Gold Award: Integrated Psychiatric Treatment for Survivors of Intimate Partner
      Violence at the Bronx Family Justice Center.

PMID- 30277436
TI  - National Trends in Peer Specialist Certification.

PMID- 30277437
TI  - Ordering Abstinence: How Far Can Courts Go in Requiring Offenders to Remain
      Substance Free?
AB  - Courts routinely order defendants into treatment for substance use, requiring
      them to remain abstinent. A recent Massachusetts challenge to this practice
      claimed holding offenders responsible for behavior they could not control was
      unfair. Had the challenge been successful, it would have called into question the
      constitutionality of the successful drug court model, which is also applied in
      probation and parole settings. In rejecting the defendant's claims, the court
      made clear its skepticism that substance use disorders result in a complete loss
      of control over drug use and its reluctance to interfere with an established
      approach to problematic substance use.

PMID- 30277438
TI  - Use of Medicaid Web Portals for Outpatient Electronic Pharmaceutical Data.

PMID- 30277439
TI  - Culturally Congruent Intensive Case Management Service for Three Refugee
      Communities.

PMID- 30277440
TI  - Health Screening and Follow-up Care Among Medicaid Beneficiaries With Serious
      Mental Illness Enrolled in Managed Care Plans.

PMID- 30277441
TI  - Prioritizing Safety Among Patients With Serious Mental Illness.

PMID- 30277442
TI  - Radiomic MRI Phenotyping of Glioblastoma: Improving Survival Prediction.
AB  - Purpose To investigate whether radiomic features at MRI improve survival
      prediction in patients with glioblastoma multiforme (GBM) when they are
      integrated with clinical and genetic profiles. Materials and Methods Data in
      patients with a diagnosis of GBM between December 2009 and January 2017 (217
      patients) were retrospectively reviewed up to May 2017 and allocated to training
      and test sets (3:1 ratio). Radiomic features (n = 796) were extracted from
      multiparametric MRI. A random survival forest (RSF) model was trained with the
      radiomic features along with clinical and genetic profiles (O-6-methylguanine-DNA
      methyltransferase promoter methylation and isocitrate dehydrogenase 1 mutation
      statuses) to predict overall survival (OS) and progression-free survival (PFS).
      The RSF models were validated on the test set. The incremental values of radiomic
      features were evaluated by using the integrated area under the receiver operating
      characteristic curve (iAUC). Results The 217 patients had a mean age of 57.9
      years, and there were 87 female patients (age range, 22-81 years) and 130 male
      patients (age range, 17-85 years). The median OS and PFS of patients were 352
      days (range, 20-1809 days) and 264 days (range, 21-1809 days), respectively. The
      RSF radiomics models were successfully validated on the test set (iAUC, 0.652
      [95% confidence interval {CI}, 0.524, 0.769] and 0.590 [95% CI: 0.502, 0.689] for
      OS and PFS, respectively). The addition of a radiomics model to clinical and
      genetic profiles improved survival prediction when compared with models
      containing clinical and genetic profiles alone (P = .04 and .03 for OS and PFS,
      respectively). Conclusion Radiomic MRI phenotyping can improve survival
      prediction when integrated with clinical and genetic profiles and thus has
      potential as a practical imaging biomarker. (c) RSNA, 2018 Online supplemental
      material is available for this article. See also the editorial by Jain and Lui in
      this issue.

PMID- 30277443
TI  - Does Nonenhanced CT-based Quantification of Abdominal Aortic Calcification
      Outperform the Framingham Risk Score in Predicting Cardiovascular Events in
      Asymptomatic Adults?
AB  - Purpose To determine if abdominal aortic calcification (AAC) at CT predicts
      cardiovascular events independent of Framingham risk score (FRS). Materials and
      Methods For this retrospective study, electronic health records for 829
      asymptomatic patients (mean age, 57.9 years; 451 women, 378 men) who underwent
      nonenhanced CT colonography screening between April 2004 and March 2005 were
      reviewed for subsequent cardiovascular events; mean follow-up interval was 11.2
      years +/- 2.8 (standard deviation). Institutional review board approval was
      obtained. CT-based AAC was retrospectively quantified as a modified Agatston
      score by using a semiautomated tool. Kaplan-Meier curves and Cox proportional
      hazards models were used for time-to-event analysis; receiver operating
      characteristic curves and net reclassification improvement compared predictive
      abilities of AAC and FRS. Results An index cardiovascular event occurred after CT
      in 156 (19%) of 829 patients (6.7 years +/- 3.5, including heart attack in 39
      [5%] and death in 79 [10%]). AAC was higher in the cardiovascular event cohort
      (mean AAC, 3478 vs 664; P < .001). AAC was a strong predictor of cardiovascular
      events at both univariable and multivariable Cox modeling, independent of FRS (P
      < .001). Kaplan-Meier plots showed better separation with AAC over FRS. The area
      under the receiver operating characteristic curve (AUC) was higher for AAC than
      FRS at all evaluated time points (eg, AUC of 0.82 vs 0.64 at 2 years; P = .014).
      By using a cutoff point of 200, AAC improved FRS risk categorization with net
      reclassification improvement of 35.4%. Conclusion CT-based abdominal aortic
      calcification was a strong predictor of future cardiovascular events,
      outperforming the Framingham risk score. This finding suggests a potential
      opportunistic role in abdominal nonenhanced CT scans performed for other clinical
      indications. (c) RSNA, 2018.

PMID- 30277444
TI  - How Far Are We from Using Radiomics Assessment of Gliomas in Clinical Practice?

PMID- 30277445
TI  - Microcalcifications Detected at Screening Mammography: Synthetic Mammography and
      Digital Breast Tomosynthesis versus Digital Mammography.
AB  - Purpose To compare the performance of two-dimensional synthetic mammography (SM)
      plus digital breast tomosynthesis (DBT) versus conventional full-field digital
      mammography (FFDM) in the detection of microcalcifications on screening
      mammograms. Materials and Methods In this retrospective multireader observer
      study, 72 consecutive screening mammograms recalled for microcalcifications from
      June 2015 through August 2016 were evaluated with both FFDM and DBT. The data set
      included 54 mammograms with benign microcalcifications and 18 mammograms with
      malignant microcalcifications, and 20 additional screening mammograms without
      microcalcifications used as controls. FFDM alone was compared to synthetic
      mammography plus DBT. Four readers independently reviewed each data set and
      microcalcification recalls were tabulated. Sensitivity and specificity for
      microcalcification detection were calculated for SM plus DBT and for FFDM alone.
      Interreader agreement was calculated with Fleiss kappa values. Results Reader
      agreement was kappa value of 0.66 (P < .001) for FFDM and 0.63 (P < .001) for SM
      plus DBT. For FFDM, the combined reader sensitivity for all microcalcifications
      was 80% (229 of 288; 95% confidence interval [CI]: 74%, 84%) and for malignant
      microcalcifications was 92% (66 of 72; 95% CI: 83%, 97%). For SM plus DBT, the
      combined reader sensitivity for all microcalcifications was 75% (215 of 288; 95%
      CI: 69%, 80%) and for malignant microcalcifications was 94% (68 of 72; 95% CI:
      86%, 98%). For FFDM, the combined reader specificity for all microcalcifications
      was 98% (78 of 80; 95% CI: 91%, 100%) and for malignant microcalcifications was
      98% (78 of 80; 95% CI: 91%, 100%). For SM plus DBT, combined reader specificity
      for all microcalcifications was 95% (76 of 80; 95% CI: 88%, 99%) and for
      malignant microcalcifications was 95% (76 of 80; 95% CI: 88%, 99%). Mixed-effects
      model concluded no differences between modalities (-0.03; 95% CI: -0.08, 0.01; P
      = .13). Conclusion Relative to full-field digital mammography, synthetic
      mammography plus digital breast tomosynthesis had similar sensitivity and
      specificity for the detection of microcalcifications previously identified for
      recall at screening mammography. (c) RSNA, 2018 See also the editorial by Bae and
      Moon in this issue.

PMID- 30277446
TI  - PD-1 Blockade-induced Inflammatory Arthritis.

PMID- 30277447
TI  - Is Synthetic Mammography Comparable to Digital Mammography for Detection of
      Microcalcifications in Screening?

PMID- 30277448
TI  - Are Fast Complex Movements Unimaginable? Pupillometric Studies of Motor Imagery
      in Expert Piano Playing.
AB  - Motor imagery (MI; mental simulation of actions) shares certain mental
      representations and processes with executed movement (ME). This neurocognitive
      overlap between MI and ME may explain why the systematic use of MI improves
      skilled performance in numerous domains. Unfortunately, the attentional
      mechanisms underlying MI remain unresolved. Therefore, the present studies
      investigated the role of attentional effort (as measured by pupil dilation) in
      MI. We evaluated the effects of movement complexity and speed on expert pianists'
      pupil dilation as they physically executed and used MI to perform easy/complex
      and slow/fast music phrases. Results revealed that easy movements required
      similar levels of attentional effort during MI and ME. However, during complex
      movements performed at a fast speed, the correspondence between execution and
      imagery of movement was disrupted.

PMID- 30277449
TI  - Feasibility of an Internet-based positive psychological intervention for
      hemodialysis patients with symptoms of depression.
AB  - BACKGROUND: Depression is a pervasive psychological issue facing hemodialysis
      (HD) patients. Novel technology-based treatment strategies that deploy psychology
      based interventions have not been the focus for therapy and few published studies
      exist. The aim of the current trial is to determine the feasibility and
      acceptability of an Internet-based positive psychological intervention in HD
      patients with comorbid depressive symptoms. METHODS: HD patients (n = 14) with
      elevated symptoms of depression were enrolled in a single-arm pre-post trial with
      clinical assessments at baseline and immediately post intervention. Chairside
      during regularly scheduled HD treatment, patients utilized a web browser to
      complete online modules promoting skills for increasing positive emotion over a 5
      week period using Apple IPads. Targeted skills included noting of daily positive
      events, gratitude, positive reappraisal, acts of kindness, and
      mindfulness/meditation. RESULTS: Twelve of 14 patients completed the program for
      an 85.7% retention rate. Participants felt satisfied with each session and
      offered consistently positive feedback. On average, participants visited the
      website 3.5 times per week. Significant improvements were evident for depressive
      symptoms (15.3 vs. 10.9; p = 0.04), as per the Center for Epidemiological Studies
      Depression Scale. CONCLUSIONS: An innovative Internet-based positive
      psychological intervention represents a feasible and useful therapeutic option
      for HD patients with depressive symptoms.

PMID- 30277450
TI  - Framework to Enhance Nurses' Use of EMR.
AB  - The ability of nurses to adopt and successfully use EMR is expected to have a
      significant impact on achieving benefits such as reduction in healthcare costs
      and improvement in healthcare quality. A review of the current research
      literature reveals issues and concerns relating to the adoption and use of EMR by
      nurses in hospital environments. This article presents a literature review of
      such issues and concerns, and suggests a framework for enhancing the adoption and
      use of EMR by nurses and hospitals.

PMID- 30277451
TI  - Examining the Return on Investment of the Breath of Life Mobile Pediatric Asthma
      Clinic in a Rural Region with Small Metropolitan Statistical Areas.
AB  - The current study sought to examine the return on investment (ROI) of a mobile
      pediatric asthma clinic in a rural region with small metropolitan statistical
      areas, in terms of reduced costs attributed to preventable emergency department
      visits, inpatient admission, school absenteeism, cost of education, and parent
      work absenteeism. For fiscal years 2015 and 2016, an average return of $1.32 and
      a community ROI of $1.45 was estimated. Estimated benefits were $445,125.00 and
      cost avoidance was $263,853.01. A mobile pediatric asthma clinics operating in
      less densely populated regions is able to yield a positive ROI.

PMID- 30277452
TI  - Hospitals' Preparedness to Treat Pediatric Patients During Mass Casualty
      Incidents.
AB  - OBJECTIVES: Little is known about the preparedness of hospitals to care for
      pediatric patients during a major incident in Japan. This study assessed the
      disaster preparedness of a children's hospital in Japan by using a disaster
      drill.Materials and MethodsWe performed a triage drill with all hospitalized
      patients. The triage tags and medical records were reviewed retrospectively. We
      determined the efficacy of triage education, the validity of the Simple Triage
      and Rapid Treatment (START) method for children, and the potential need for
      evacuation through the disaster drill. RESULTS: This study highlights 3 important
      issues about the hospital's preparedness. First, it is difficult to promote
      disaster education for staff who are not well trained on handling disasters.
      Second, the START method is suitable for children older than 5 years, but it has
      a high rate of over-triaging among younger children. Third, approximately 40% of
      patients who are coded as immediate may require transportation resources in a
      hospital evacuation. CONCLUSIONS: Our findings suggest that disaster
      preparedness, such as educating hospital staff regarding disasters and
      establishing evacuation systems for a number of pediatric patients when a
      disaster happens, is essential for caring for hospitalized children during a mass
      casualty incident. (Disaster Med Public Health Preparedness. 2018;page 1 of 4).

PMID- 30277453
TI  - Longitudinal effects of acculturation and enculturation on mental health: Does
      the measure of matter?
AB  - A great deal of research has focused on acculturation and enculturation, which
      represent the processes of adapting to a new culture. Despite this growing
      literature, results have produced inconsistent findings that may be attributable
      to differences in terms of the instruments used to assess acculturation and
      enculturation. Utilizing a 3-year longitudinal data set (with 1-year lags between
      assessments), the present study explored the psychometric properties of the
      Bicultural Involvement Questionnaire-Short Version (BIQ-S) and the Acculturation
      Rating Scale for Mexican Americans II (ARSMA-II) and examined the overlap between
      changes in these measures as they relate to internalizing and externalizing
      problem behavior. The present sample consisted of 216 immigrant Latino youth (43%
      boys; mean age 13.6 years at baseline; SD = 1.44 years, range 10 to 17).
      Exploratory structural equation modeling identified factor structures for the BIQ
      S and ARSMA-II that diverged from their hypothesized structure. Growth curve
      models also indicate divergence between the BIQ-S and ARSMA-II in terms of change
      in acculturation and enculturation processes. Finally, the present findings
      emphasized that measures of acculturation and enculturation are not equivalent in
      terms of their effects on internalizing and externalizing problems.

PMID- 30277454
TI  - The effects of Trolox on the quality of sperm from captive squirrel monkey during
      liquefaction in the extender ACP-118TM.
AB  - SummaryThe aim of this study was to evaluate the effect of incubating semen for
      different periods (90, 270 or 450 min) with or without Trolox(r) (100 or 150 uM)
      on the quality of sperm from Saimiri collinsi. Sperm motility, vigour, and plasma
      membrane integrity (PMI) were evaluated in both fresh semen and semen incubated
      for different time periods, i.e. 90, 270 or 450 min of incubation.
      Supplementation of semen extender with Trolox(r) 100 uM improved sperm motility,
      vigour and PMI for up to 270 min of incubation.

PMID- 30277455
TI  - Effect of chromium supplementation on growth performance, meal pattern, metabolic
      and antioxidant status and insulin sensitivity of summer-exposed weaned dairy
      calves.
AB  - Stressful situations may result in serum chromium (Cr) depletion with increased
      urinary excretion of the mineral and increased Cr requirements. The objective of
      this study was to investigate the effects of Cr supplementation on growth
      performance, feeding behavior, blood metabolites and hormones, indicators of
      oxidative stress and glucose-insulin kinetics of summer-exposed weaned dairy
      calves. In total, 48 Holstein female calves (63 days of age; 77.0+/-1.45 kg of
      BW) were assigned randomly to one of two treatments: (1) a control group with no
      supplemental Cr (Cr-), and (2) a supplemental Cr group (Cr+) to supply 0.05 mg Cr
      as Cr-methionine/kg of BW0.75. Chromium was provided in the starter feed and
      adjusted weekly based on BW over the experimental period. All calves were on
      experiment for 4 weeks after weaning. The average maximum temperature-humidity
      index was 76.1 units during the study period, indicating a mild degree of
      environmental heat load. Results indicated that in summer-exposed dairy calves,
      increased dietary Cr provision tended to decrease fecal score, tended to change
      rumination pattern, increased antioxidant capacity by increasing serum
      concentration of catalase, but had no effects on growth performance, metabolic
      status or peripheral glucose and insulin metabolism.

PMID- 30277456
TI  - Excess Mortality and Causes Associated with Chikungunya, Puerto Rico, 2014-2015.
AB  - During 2014-2015, a total of 31 deaths were associated with the first chikungunya
      epidemic in Puerto Rico. We analyzed excess mortality from various causes for the
      same months during the previous 4 years and detected 1,310 deaths possibly
      attributable to chikungunya. Our findings raise important questions about
      increased mortality rates associated with chikungunya.

PMID- 30277457
TI  - Apathy alters emotional arousal in chronic schizophrenia.
AB  - BACKGROUND: Within the heterogeneity of schizophrenia, apathy constitutes an
      independent cluster of negative symptoms associated with poor outcomes. Attempts
      to identify an emotional deficit in patients who have schizophrenia with negative
      symptoms have yielded mixed results, and studies that focus on the relationship
      between apathy and emotional disorders are lacking. METHODS: We set out to remedy
      this shortcoming using a validated battery of film excerpts to induce positive
      and negative emotions in patients with chronic schizophrenia with (n = 20) or
      without (n = 20) apathy, and in controls (n = 20) comparable for age, sex and
      socioeconomic status. We assessed emotions using an innovative but validated
      technique to evaluate tonic and phasic electrodermal activity and subjective
      feelings using a standardized visual analogue scale. RESULTS: Using a qualitative
      measure of apathy, we did not find a specific decrease in tonic activity during
      the induction of positive emotions. However, we did observe that patients with
      apathy showed reduced tonic activity independent of valence (i.e., for both
      positive and negative emotions) compared with controls and patients without
      apathy. Moreover, the quantitative measure of apathy (Apathy Evaluation Scale)
      was the only significant factor, explaining 24% of the variance in tonic activity
      during induction of positive emotions after controlling for confounding factors.
      LIMITATIONS: Electrodermal activity was the only physiologic measure we acquired.
      We induced several emotions sequentially that might have overlapped with each
      other, but we added an emotional "washout" period and randomized the order of
      each film excerpt to limit this possibility. CONCLUSION: Taken together, these
      results suggest that apathy in schizophrenia could impair tonic activity during
      positive emotions. Treatments aimed at enhancing positive emotions may help
      alleviate apathy in schizophrenia.

PMID- 30277460
TI  - Bioresorbable Vascular Scaffolds in coronary chronic total occlusions. Clinical,
      vasomotor and optical coherence tomography findings at 3-year follow-up (ABSORB
      CTO study).
AB  - AIMS: Percutaneous treatment of coronary chronic total occlusion (CTO) is
      associated with important arterial remodelling after successful recanalization.
      Bioresorbable vascular scaffold (BVS) implantation in CTO has been shown feasible
      and can be of interest when the scaffold achieves complete bioresorption. We
      sought to evaluate the 3-year results in terms of clinical events, serial imaging
      outcomes and the vasomotion response in CTO lesions successfully treated with
      BVS. METHODS AND RESULTS: A total of 33 patients (35 CTO lesions) successfully
      treated with BVS were included in ABSORB-CTO study. Clinical outcomes,
      quantitative coronary angiography (QCA) and optical coherence tomography (OCT)
      assessment were analysed at 1-and 3-year follow-up. Vasomotion examination was
      also performed at 3 years. At 3-year, cumulative target vessel re-occlusion was
      observed in 4 lesions(11.4%). By QCA, in-scaffold segment presented a lumen loss
      of 0.23+/-0.46 mm compared with baseline procedure (p=0.001) and a lumen gain of
      0.05+/-0.29 mm between 1 and 3 years (p=0.220). By OCT the mean neointimal area
      stenosis progressed from 11.45% at 12 months to 17.10% at 36 months (p<0.001) and
      mean scaffold area increased continuously at 12 (+12%;p<0.001) and at 36 months
      (+14.85%;p=0.001). Late acquired incomplete scaffold apposition (LAISA) observed
      at 12 months in 3 patients was completely undetectable at 3 years. Most of cases
      responded to endothelial-dependent vasomotor stimuli (69%). Vasoconstriction to
      acetylcholine was the predominant response (45%). CONCLUSIONS: Successful
      recanalization of coronary-CTO with BVS implantation is associated with
      favourable clinical and imaging outcomes. Despite vessel motility restoration,
      successfully treated CTO remain with signs of endothelial dysfunction.

PMID- 30277461
TI  - First experience with MitraClip XTR device for severe mitral valve prolapse
      (Barlow's disease).

PMID- 30277458
TI  - Rif1 inhibits replication fork progression and controls DNA copy number in
      Drosophila.
AB  - Control of DNA copy number is essential to maintain genome stability and ensure
      proper cell and tissue function. In Drosophila polyploid cells, the SNF2-domain
      containing SUUR protein inhibits replication fork progression within specific
      regions of the genome to promote DNA underreplication. While dissecting the
      function of SUUR's SNF2 domain, we identified an interaction between SUUR and
      Rif1. Rif1 has many roles in DNA metabolism and regulates the replication timing
      program. We demonstrate that repression of DNA replication is dependent on Rif1.
      Rif1 localizes to active replication forks in a partially SUUR-dependent manner
      and directly regulates replication fork progression. Importantly, SUUR associates
      with replication forks in the absence of Rif1, indicating that Rif1 acts
      downstream of SUUR to inhibit fork progression. Our findings uncover an
      unrecognized function of the Rif1 protein as a regulator of replication fork
      progression.

PMID- 30277462
TI  - Pre-infarction Angina and Culprit Lesion Morphologies in Patients with a First ST
      segment Elevation Acute Myocardial Infarction: Insights from In Vivo Optical
      Coherence Tomography.
AB  - AIMS: This study aimed to evaluate the relationship between pre-infarction angina
      (PIA) and in vivo culprit lesion characteristics as assessed by intravascular
      optical coherence tomography (OCT) in patients with a first ST-segment elevation
      myocardial infarction (STEMI). METHODS AND RESULTS: A total of 305 consecutive
      patients with a first STEMI who underwent OCT imaging of culprit lesions during
      primary percutaneous coronary intervention (PCI) were prospectively enrolled. OCT
      findings of the culprit plaque were compared between patients with (n=206) and
      without PIA (n=99). Patients with PIA showed lower rates of thin-cap
      fibroatheroma (TCFA) (62.6% vs. 80.8%, P=0.001) and plaque rupture (56.8% vs.
      72.7%, P=0.007), smaller maximum ruptured cavity areas (1.10+/-1.04 mm2 vs.
      1.53+/-1.20 mm2, P=0.002), and more severe residual luminal narrowing (P=0.015)
      with a higher incidence of white residual thrombus (68.4% vs. 50.0%, P=0.003) at
      the culprit lesions than patients without PIA. No significant differences in
      clinical outcomes were observed at the 1-year follow-up. CONCLUSIONS: In patients
      with a first STEMI, PIA was significantly associated with a lower incidence of
      TCFA and plaque rupture, a smaller ruptured cavity area, more white residual
      thrombi, and more severe lumen stenosis at the culprit lesions. TRIAL
      REGISTRATION NUMBER: NCT03107624.

PMID- 30277463
TI  - Paclitaxel density and clinical efficacy of drug-coated balloon angioplasty for
      femoropopliteal artery disease. Meta-analysis and adjusted indirect comparison of
      20 randomized trials.

PMID- 30277459
TI  - Integrated systems analysis reveals conserved gene networks underlying response
      to spinal cord injury.
AB  - Spinal cord injury (SCI) is a devastating neurological condition for which there
      are currently no effective treatment options to restore function. A major
      obstacle to the development of new therapies is our fragmentary understanding of
      the coordinated pathophysiological processes triggered by damage to the human
      spinal cord. Here, we describe a systems biology approach to integrate decades of
      small-scale experiments with unbiased, genome-wide gene expression from the human
      spinal cord, revealing a gene regulatory network signature of the
      pathophysiological response to SCI. Our integrative analyses converge on an
      evolutionarily conserved gene subnetwork enriched for genes associated with the
      response to SCI by small-scale experiments, and whose expression is upregulated
      in a severity-dependent manner following injury and downregulated in functional
      recovery. We validate the severity-dependent upregulation of this subnetwork in
      rodents in primary transcriptomic and proteomic studies. Our analysis provides
      systems-level view of the coordinated molecular processes activated in response
      to SCI.

PMID- 30277464
TI  - First prospective multicenter experience with left distal transradial approach
      for coronary chronic total occlusion interventions using a 7-french glidesheath
      slender.
AB  - AIMS: to assess the feasibility and safety of the left distal transradial artery
      (LDTRA) approach using a 7 Fr Glidesheath Slender for chronic total occlusion
      (CTO) percutaneous coronary interventions (PCIs). METHODS AND RESULTS: From March
      to May 2018 a total of 41 consecutive CTO PCIs were performed through LDTRA
      access using a 7 Fr Glidesheath Slender. Technical and procedural success,
      defined as achievement of technical success using the initially selected LDTRA
      access with no in-hospital mayor adverse cardiovascular events (MACE), were
      respectively 90,3% and 78%. Failure in achieving LDTRA access was 17,1%. There
      were no vascular access-site complications such as no post-procedural LDRAOs.
      Doppler ultrasound imaging of the left distal radial artery at 1 month was
      available in 67,6% of patients with only one case (4.3%) of LDRAO in a female
      patient. CONCLUSIONS: LDTRA approach using a 7 Fr Glidesheath Slender for CTO
      PCIs is feasible and associated with high rate of procedural success and low rate
      of vascular access-site complications.

PMID- 30277465
TI  - Prospective Evaluation of the Non-Compliant Severe Hemophilia Patients.

PMID- 30277467
TI  - Thermal conductivity of silicon nanowire forests.
AB  - A large amount of parallel silicon nanowires, placed perpendicularly to a silicon
      substrate (silicon nanowire forests), have been contacted and assembled in order
      to fabricate legs of a thermoelectric generator. This paper reports the
      measurement of the main parameter for thermoelectric applications, which is the
      thermal conductivity. The reported value, which confirms the strong reduction of
      the thermal conductivity in nanostructures, is measured on a large amount (>107)
      of parallel nanowires with a diameter variable in the range 60-120 nm, and takes
      into account eventual non-uniformities which are unavoidable on surfaces of
      several mm2. As silicon nanowire forests are very thin, it has been necessary to
      develop a suitable measurement apparatus. The fabrication of devices based on
      silicon nanowire forests, the apparatus and the measurement procedure, as well as
      the the results, are illustrated and discussed.

PMID- 30277466
TI  - A comparison between two dolutegravir-based two-drug regimens as switch
      strategies in a multicentre cohort of HIV-1-infected patients.
AB  - BACKGROUND: Two-drug regimens are increasingly used in clinical practice as
      switch strategies. We compared the efficacy and safety of two dolutegravir (DTG)
      based dual therapies: DTG plus lamivudine (3TC group) versus DTG plus rilpivirine
      (RPV group). METHODS: In a multicentre cohort of virologically suppressed (HIV
      RNA <50 copies/ml) HIV+ patients switching to DTG+3TC or DTG+RPV we analysed the
      incidence of virological failures (VF) and treatment discontinuations (TD), as
      well as their predictors. RESULTS: We analysed 416 patients, 229 in the 3TC group
      and 187 in the RPV group. The 3TC group, during 344.4 person-years of follow-up
      (PYFU), had 10 VF without the emergence of resistance mutations, while 30
      patients discontinued the regimen. In the RPV group, during 371.0 PYFU, there
      were 5 VF (1 developed non-nucleoside reverse transcriptase inhibitor mutations
      Y181C and E138Q) and 13 TD. The estimated probability of remaining free from VF
      at 48 weeks showed no significant difference between groups (log-rank 0.172). We
      found a higher risk of VF in patients with peak viral load >500,000 copies/ml in
      both treatment groups (log-rank P=0.004 in each group). The estimated probability
      of remaining in the study regimen at week 48 was 89.0% with DTG+3TC and 96.1%
      with DTG+RPV (log-rank 0.015). After adjusting for potential confounders,
      treatment group was not associated with TD. A significant decrease in total
      cholesterol was observed at week 48 in both groups while renal function remained
      unchanged. CONCLUSIONS: DTG+RPV and DTG+3TC were compared in populations with
      different characteristics in clinical practice: both regimens showed good
      effectiveness and improved lipid profile.

PMID- 30277468
TI  - In situ and ex situ NMR for battery research.
AB  - A rechargeable battery stores readily convertible chemical energy to operate a
      variety of devices such as mobile phones, laptop computers, electric automobiles,
      etc. A battery generally consists of four components: a cathode, an anode, a
      separator and electrolytes. The properties of these components jointly determine
      the safety, the lifetime, and the electrochemical performance. They also include,
      but are not limited to, the power density and the charge as well as the recharge
      time/rate associated with a battery system. An extensive amount of research is
      dedicated to understanding the physical and chemical properties associated with
      each of the four components aimed at developing new generations of battery
      systems with greatly enhanced safety and electrochemical performance at a
      significantly reduced cost for large scale applications. Advanced
      characterization tools are a prerequisite to fundamentally understanding battery
      materials. Considering that some of the key electrochemical processes can only
      exist under in situ conditions, which can only be captured under working battery
      conditions when electric wires are attached and current and voltage are applied,
      make in situ detection critical. Nuclear magnetic resonance (NMR), a non-invasive
      and atomic specific tool, is capable of detecting all phases, including
      crystalline, amorphous, liquid and gaseous phases simultaneously and is ideal for
      in situ detection on a working battery system. Ex situ NMR on the other hand can
      provide more detailed molecular or structural information on stable species with
      better spectral resolution and sensitivity. The combination of in situ and ex
      situ NMR, thus, offers a powerful tool for investigating the detailed
      electrochemistry in batteries.

PMID- 30277469
TI  - Two-dimensional noise reconstruction in proton computed tomography using distance
      driven filtered back-projection of simulated projections.
AB  - We present a formalism for two-dimensional (2D) noise reconstruction in proton
      computed tomography (pCT). This is necessary for the application of fluence
      modulated pCT (FMpCT) since it permits image noise prescription and the
      corresponding proton fuence optimization. We aimed at extending previously
      published formalisms to account for the impact of multiple Coulomb scattering
      (MCS) on projection noise, and the use of filtered back projection (FBP)
      reconstruction along curved paths with distance driven binning (DDB). 2D noise
      reconstruction for a beam of protons with parallel initial momentum vectors, and
      for projections binned both at the rear tracker and with DDB, was established.
      Monte Carlo (MC) simulations of pCT scans of a water cylinder were employed to
      generate pCT projections and to calculate their noise for use in 2D noise
      reconstruction. These were compared to results from an analytical model
      accounting for MCS for rear tracker binning as well as against the previously
      published central pixel model which ignores MCS. Image noise reconstructed with
      the formalism for rear tracker binning and DDB were compared to MC results using
      annular regions of interest (ROIs). Agreement better than 8% was obtained between
      the noise of projections calculated with MC simulation and our model. Noise from
      annular ROIs agreed with our noise reconstructions for rear tracker binning and
      DDB. The central pixel model ignoring MCS underestimated projection and thus
      image noise by up to 40% towards the object's edge. The use of DDB decreased the
      image noise towards the object's edge when compared to rear tracker binning and
      yielded more uniform noise throughout the image. MCS should not be neglected when
      predicting image noise for pixels away from the center of an object in a pCT scan
      due to the increasing influence of the gradient of the object's hull closer to
      the edges.

PMID- 30277470
TI  - Porous SnO2-Cu x O nanocomposite thin film on carbon nanotubes as electrodes for
      high performance supercapacitors.
AB  - Metal oxides are promising materials for supercapacitors due to their high
      theoretical capacitance. However, their poor electrical conductivity is a major
      challenge. Hybridization with conductive nanostructured carbon-based materials
      such as carbon nanotubes (CNTs) has been proposed to improve the conductivity and
      increase the surface area. In this work, CNTs are used as a template for
      synthesizing porous thin films of SnO2-CuO-Cu2O (SnO2-Cu x O) via an electroless
      deposition technique. Tin, with its high wettability and electrical conductivity,
      acts as an intermediate layer between copper and the CNTs and provides a strong
      interaction between them. We also observed that by controlling the interfacial
      characteristics of CNTs and varying the composition of the electroless bath, the
      SnO2-Cu x O thin film morphology can be easily manipulated. Electrochemical
      characterizations show that CNT/SnO2-Cu x O nanocomposite possesses
      pseudocapacitive behavior that reaches a specific capacitance of 662 F g-1 and
      the retention is 94% after 5000 cycles, which outperforms any known copper and
      tin-based supercapacitors in the literature. This excellent performance is mainly
      attributed to high specific surface area, small particle size, the synergistic
      effect of Sn, and conductivity improvement by using CNTs. The combination of CNTs
      and metal oxides holds promise for supercapacitors with improved performance.

PMID- 30277472
TI  - Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus
      macaques.
AB  - In the era of combined antiretroviral therapy (cART), lung diseases such as
      chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD) are
      common among persons living with HIV (PLWH), particularly smokers. Although
      smoking is highly prevalent among PLWH, HIV may be an independent risk factor for
      lung diseases; however, the role of HIV and cigarette smoke (CS) and their
      potential interaction in the development of chronic lung diseases among PLWH has
      not been delineated. To investigate this interaction, cynomolgus macaques were
      exposed to CS and/or simian-adapted human immunodeficiency virus (SHIV) and
      treated with cART. The development of CB and the lung functions were evaluated
      following CS+/-SHIV treatment. The results showed that in the lung, SHIV was a
      strong independent risk factor for goblet cell metaplasia/hyperplasia and mucus
      formation, MUC5AC synthesis, loss of tight junction proteins, and increased
      expression of Th2 cytokines/transcription factors. In addition, SHIV and CS
      synergistically reduced lung function and increased extrathoracic tracheal ring
      thickness. Interestingly, SHIV infection generated significant numbers of HIV
      gp120+ epithelial cells (HGECs) in small airways and alveoli, and their numbers
      doubled in CS+SHIV-infected lungs. We conclude that even with cART, SHIV
      independently induces CB and pro-COPD changes in the lung, and the effects are
      exacerbated by CS.

PMID- 30277471
TI  - CD84 regulates PD-1/PD-L1 expression and function in chronic lymphocytic
      leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by clonal proliferation and
      progressive accumulation of mature B lymphocytes in the peripheral blood,
      lymphoid tissues, and bone marrow. CLL is characterized by profound immune
      defects leading to severe infectious complications. T cells are numerically,
      phenotypically, and functionally highly abnormal in CLL, with only limited
      ability to exert antitumor immune responses. Exhaustion of T cells has also been
      suggested to play an important role in antitumor responses. CLL-mediated T cell
      exhaustion is achieved by the aberrant expression of several inhibitory molecules
      on CLL cells and their microenvironment, prominently the programmed cell death
      ligand 1/programmed cell death 1 (PD-L1/PD-1) receptors. Previously, we showed
      that CD84, a member of the SLAM family of receptors, bridges between CLL cells
      and their microenvironment. In the current study, we followed CD84 regulation of
      T cell function. We showed that cell-cell interaction mediated through human and
      mouse CD84 upregulates PD-L1 expression on CLL cells and in their
      microenvironment and PD-1 expression on T cells. This resulted in suppression of
      T cell responses and activity in vitro and in vivo. Thus, our results demonstrate
      a role for CD84 in the regulation of immune checkpoints by leukemia cells and
      identify CD84 blockade as a therapeutic strategy to reverse tumor-induced immune
      suppression.

PMID- 30277473
TI  - beta-Blockers and bone health.
AB  - Bone metabolism is controlled by endocrine, paracrine, and inflammatory signals
      that continuously operate in health and disease. While these signals are critical
      for skeletal adaptation during development, longitudinal growth, and repair,
      disturbances such as sex hormone deficiency or chronic inflammation have
      unambiguously been linked to bone loss and skeletal fragility across species. In
      the current issue of the JCI, Khosla et al. evaluated the role of sympathetic
      outflow and present evidence to support the idea that the sympathetic nervous
      system regulates bone metabolism in humans, primarily via the beta1-adrenergic
      receptor.

PMID- 30277474
TI  - E-cadherin expression on multiple myeloma cells activates tumor-promoting
      properties in plasmacytoid DCs.
AB  - Plasmacytoid dendritic cells (pDCs) play a key role in antiviral responses by
      producing type-1 IFNs. However, recent studies showed that pDCs induce immune
      suppression and promote tumor growth in human ovarian cancer and myeloma. The
      molecular mechanisms underlying pDC acquisition of these properties are unknown.
      Here we show that human pDCs activated by CpG inhibited growth and induced
      apoptosis in myeloma cells via secreted IFN-alpha, but direct contact with
      myeloma cells converted pDCs into tumor-promoting cells by suppressing pDC IFN
      alpha production. E-cadherin, expressed on both myeloma cells and pDCs, mediated
      these effects via a homophilic interaction - activation of E-cadherin signaling
      upregulated and activated TNFAIP3 to interact with TLR9, resulting in TLR9
      ubiquitination and degradation, and inhibition of IFN-alpha production in pDCs.
      These findings were supported by an in vivo study in which pDC depletion induced
      tumor regression and better survival in the Vk*MYC myeloma mouse model.
      Furthermore, IFNAR1 expression level positively correlated to overall survival of
      patients with multiple myeloma (MM), and the IFN-alpha level in patient bone
      marrow was significantly lower than that in marrow of healthy individuals. This
      study reveals a novel mechanism underlying how MM tumors educate pDCs in their
      microenvironment and provides new targets for improving the treatment of MM.

PMID- 30277477
TI  - ATAC-ing the mechanisms of renin regulation.
AB  - Renin-expressing cells have been conserved through evolution and maintain blood
      pressure and fluid homeostasis. Lack of availability of tools to study the
      specifics of renin regulation has limited advances in this field. In the current
      issue of the Journal of Clinical Investigation, Martinez and colleagues used the
      genome-wide assessment of the chromatin status of cells and uncovered a unique
      set of super-enhancers that determine the identity of renin cells. The renin
      super-enhancers play a key role in the molecular memory of renin cell function, a
      mechanism at the core of preserving homeostasis.

PMID- 30277478
TI  - PD-L1 in tumor microenvironment mediates resistance to oncolytic immunotherapy.

PMID- 30277479
TI  - Billing and Volunteers Substantially Reduced School-Located Influenza Vaccination
      Costs, 2 Oregon Counties, 2010-2011.
AB  - BACKGROUND AND OBJECTIVES: After the 2009 pandemic influenza seasons, the
      financial sustainability of school-located vaccination (SLV) clinics drew much
      attention. This study estimated and compared the labor costs of SLV clinics and
      reimbursements for influenza vaccinations for students attending 5 schools in 2
      Oregon counties during 2010-2011. DESIGN/SETTING: Using a biweekly, Web-based
      survey, staff and volunteers prospectively tracked the time they spent on SLV
      clinic planning, implementation, and billing. They also tracked claims submitted
      and reimbursements by payment source. MAIN OUTCOME MEASURE: We report labor hours
      and associated costs for implementing school-based vaccination clinics; number of
      claims submitted and the reimbursement rate; and total and net costs. RESULTS: In
      county A, 260 doses were administered at a total cost of $5009 and received $3620
      in payment. For county B, 165 doses were administered at a cost of $5598 and
      received $3807 in payments. With billing, the net cost per dose decreased from
      $19.74 to $8.57 and $38.08 to $16.17, for county A and county B, respectively.
      CONCLUSIONS: Reimbursements reduced cost per dose by 48% across SLV clinics
      across both Oregon counties. Local health departments can bill local health
      insurers to offset costs for implementing school-based vaccination clinics.
      Efforts to set up billing processes require dedicated billing staff who can
      effectively manage claims submission processes with multiple health insurers.

PMID- 30277476
TI  - Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac
      allograft survival.
AB  - The targeted delivery of therapeutic drugs to lymph nodes (LNs) provides an
      unprecedented opportunity to improve the outcomes of transplantation and immune
      mediated diseases. The high endothelial venule is a specialized segment of LN
      vasculature that uniquely expresses peripheral node addressin (PNAd) molecules.
      PNAd is recognized by MECA79 mAb. We previously generated a MECA79 mAb-coated
      microparticle (MP) that carries tacrolimus. Although this MP trafficked to LNs,
      it demonstrated limited therapeutic efficacy in our transplant model. Here, we
      have synthesized a nanoparticle (NP) as a carrier of anti-CD3, and optimized the
      conjugation strategy to coat the NP surface with MECA79 mAb (MECA79-anti-CD3-NP)
      to enhance LN accumulation. As compared with nonconjugated NPs, a significantly
      higher quantity of MECA79-NPs accumulated in the draining lymph node (DLN). Many
      MECA79-NPs underwent internalization by T cells and dendritic cells within the
      LNs. Short-term treatment of murine cardiac allograft recipients with MECA79-anti
      CD3-NP resulted in significantly prolonged allograft survival in comparison with
      the control groups. Prolonged graft survival following treatment with MECA79-anti
      CD3-NP was characterized by a significant increase in intragraft and DLN Treg
      populations. Treg depletion abrogated the prolongation of heart allograft
      survival. We believe this targeted approach of drug delivery could redefine the
      methods of administering immune therapeutics in transplantation.

PMID- 30277475
TI  - Targeting nuclear receptor NR4A1-dependent adipocyte progenitor quiescence
      promotes metabolic adaptation to obesity.
AB  - Adipocyte turnover in adulthood is low, suggesting that the cellular source of
      new adipocytes, the adipocyte progenitor (AP), resides in a state of relative
      quiescence. Yet the core transcriptional regulatory circuitry (CRC) responsible
      for establishing a quiescent state and the physiological significance of AP
      quiescence are incompletely understood. Here, we integrate transcriptomic data
      with maps of accessible chromatin in primary APs, implicating the orphan nuclear
      receptor NR4A1 in AP cell-state regulation. NR4A1 gain and loss of function in
      APs ex vivo decreased and enhanced adipogenesis, respectively. Adipose tissue of
      Nr4a1-/- mice demonstrated higher proliferative and adipogenic capacity compared
      with that of WT mice. Transplantation of Nr4a1-/- APs into the subcutaneous
      adipose tissue of WT obese recipients improved metrics of glucose homeostasis
      relative to administration of WT APs. Collectively, these data identify NR4A1 as
      a previously unrecognized constitutive regulator of AP quiescence and suggest
      that augmentation of adipose tissue plasticity may attenuate negative metabolic
      sequelae of obesity.

PMID- 30277480
TI  - Flow cytometry analysis of adrenoceptors expression in human adipose-derived
      mesenchymal stem/stromal cells.
AB  - Mesenchymal stem/stromal cells (MSCs) were identified in most tissues of an adult
      organism. MSCs mediate physiological renewal, as well as regulation of tissue
      homeostasis, reparation and regeneration. Functions of MSCs are regulated by
      endocrine and neuronal signals, and noradrenaline is one of the most important
      MSC regulators. We provided flow cytometry analysis of expression of adrenergic
      receptors on the surface of human MSCs isolated from ten different donors. We
      have found that the expression profile of adrenergic receptors in MSCs vary
      significantly between donors. We also showed that alpha1A-adrenoceptor expression
      is upregulated under the action of noradrenaline. We share our flow cytometry raw
      data, as well as processing of these data on a flow cytometry repository for
      freely downloading.

PMID- 30277481
TI  - Free-electron laser data for multiple-particle fluctuation scattering analysis.
AB  - Fluctuation X-ray scattering (FXS) is an emerging experimental technique in which
      solution scattering data are collected using X-ray exposures below rotational
      diffusion times, resulting in angularly anisotropic X-ray snapshots that provide
      several orders of magnitude more information than traditional solution scattering
      data. Such experiments can be performed using the ultrashort X-ray pulses
      provided by a free-electron laser source, allowing one to collect a large number
      of diffraction patterns in a relatively short time. Here, we describe a test data
      set for FXS, obtained at the Linac Coherent Light Source, consisting of close to
      100 000 multi-particle diffraction patterns originating from approximately 50 to
      200 Paramecium Bursaria Chlorella virus particles per snapshot. In addition to
      the raw data, a selection of high-quality pre-processed diffraction patterns and
      a reference SAXS profile are provided.

PMID- 30277482
TI  - RNA-seq of macrophages of amoeboid or mesenchymal migratory phenotype due to
      specific structure of environment.
AB  - M2-polarized macrophages have been shown to adapt their 3D migration mode to
      physical properties of surrounding extracellular matrix. They migrate in the
      integrin-mediated adhesion and proteolytic activity-dependent "mesenchymal" mode
      in stiff matrices and in the integrin and protease-independent "amoeboid" mode in
      low density, porous environments. To find out what impact the switching between
      the migration modes has on expression of both protein-coding and non-coding genes
      we employed RNA sequencing of total RNA depleted of ribosomal RNA isolated from
      macrophages migrating in either mode in 3D collagens. Differentially expressed
      genes from both categories have been detected and the changes in expression of
      selected genes were further validated with RT-qPCR. The acquired data will
      facilitate better understanding of how mechanical properties of tissue
      microenvironment reflect in macrophage immune function and how the transitions
      between mesenchymal and amoeboid migratory modes are regulated at the gene
      expression level.

PMID- 30277484
TI  - Sensing caspase-1 activity using activatable 19F MRI nanoprobes with improved
      turn-on kinetics.
AB  - Activatable 19F MRI nanoprobes for sensing caspase-1 activity were developed.
      Tandem repetition of substrate peptide sequences improved the turn-on response of
      nanoprobes, allowing detection of caspase-1 activity by 19F MRI. In vivo immune
      response was successfully imaged using the new nanoprobe.

PMID- 30277485
TI  - UV/visible light active CuCrO2 nanoparticle-SnO2 nanofiber p-n heterostructured
      photocatalysts for photocatalytic applications.
AB  - CuCrO2 nanoparticle decorated SnO2 nanofiber composites have been prepared as
      novel p-n heterostructured semiconductor photocatalysts for the degradation of
      organic pollutants in wastewater. The composite structure was achieved via drop
      casting of various amounts of hydrothermally derived CuCrO2 nanoparticles on
      electrospun SnO2 nanofibers. The microstructural and morphological features of
      each semiconductor and the formation of p-n heterojunctions between them were
      characterized. In addition, the photo-response and electrochemical properties of
      the samples were determined. The photocatalytic activity of the heterostructured
      photocatalysts was investigated systematically as a function of the amount of
      CuCrO2 nanoparticles in the samples. Experimental results showed that the optimal
      decoration amount was 0.6 wt% CuCrO2 on SnO2. This composite photocatalyst
      displayed a 41% higher rate constant value compared to pure SnO2 nanofibers in
      the degradation of methylene blue dye molecules and reached 83% degradation under
      UV/visible light irradiation after 1 h. The increase in the photocatalytic
      activity was ascribed to the incorporation of Cr3+ and Cu+ cations into the SnO2
      host lattice and the more effective electron-hole pair separation in the
      heterostructured sample. The presented data here are highly convincing in
      comparison to those of UV active p-n heterostructured photocatalysts reported
      previously in the literature. Therefore, this work opens the way to develop
      visible light active p-n heterostructured semiconductor photocatalysts using p
      type delafossites with n-type oxides.

PMID- 30277486
TI  - Lifetime and nonlinearity of modulated surface plasmon for black phosphorus
      sensing application.
AB  - Black phosphorus surface plasmon (BPSP) is a new promising candidate material for
      electromagnetic field confinement at the subwavelength scale. Here, we
      theoretically investigated the light confinement, second-order nonlinearity and
      lifetimes of tunable surface plasmons in nanostructured black phosphorus
      nanoflakes with superstrates. The grating structure can enhance the local optical
      field of the fundamental wave (FW) and second harmonic wave (SHW) due to the
      surface plasmon resonance. Based on the coupled mode theory (CMT), a theoretical
      model for the nanostructured black phosphorus was established to study the
      spectrum features of FW. The lifetimes of the plasmonic resonant modes were
      investigated with the finite difference time domain (FDTD) simulations and CMT.
      Since the permittivity of black phosphorus depends on its Fermi energy and
      electron scattering rate, the lifetimes of plasmonic absorption modes are tunable
      with both the Fermi energy and scattering rate. The intensity, wavelengths and
      spectral width of BPSP resonance modes and their lifetimes can be precisely
      controlled with the Fermi energy, scattering rate, side length and refractive
      index of the superstrate. The sensitivity is described by varying the refractive
      index of the superstrate such as an aqueous solution. We have introduced a second
      order nonlinear source to investigate the SHW of nanostructured black phosphorus.
      This paper presents the corner/edge energy distribution and the tunable lifetime
      of BPSP as well as their unprecedented capability of photon manipulation for
      second-order nonlinearity within the deep subwavelength scale. The configuration
      and method are useful for research of the absorption, lifetime of light and
      nonlinear optical processes in black phosphorus-based optoelectronic devices,
      especially the modulation and sensing applications.

PMID- 30277483
TI  - Transcriptomes of cochlear inner and outer hair cells from adult mice.
AB  - Inner hair cells (IHCs) and outer hair cells (OHCs) are the two anatomically and
      functionally distinct types of mechanosensitive receptor cells in the mammalian
      cochlea. The molecular mechanisms defining their morphological and functional
      specializations are largely unclear. As a first step to uncover the underlying
      mechanisms, we examined the transcriptomes of IHCs and OHCs isolated from adult
      CBA/J mouse cochleae. One thousand IHCs and OHCs were separately collected using
      the suction pipette technique. RNA sequencing of IHCs and OHCs was performed and
      their transcriptomes were analyzed. The results were validated by comparing some
      IHC and OHC preferentially expressed genes between present study and published
      microarray-based data as well as by real-time qPCR. Antibody-based
      immunocytochemistry was used to validate preferential expression of SLC7A14 and
      DNM3 in IHCs and OHCs. These data are expected to serve as a highly valuable
      resource for unraveling the molecular mechanisms underlying different biological
      properties of IHCs and OHCs as well as to provide a road map for future
      characterization of genes expressed in IHCs and OHCs.

PMID- 30277487
TI  - Identifying reactive organo-selenium precursors in the synthesis of CdSe
      nanoplatelets.
AB  - In the synthesis of CdSe nanoplatelets, the selenium-to-selenide reduction
      pathway is unknown. We study solvent-free growth of CdSe nanoplatelets and
      identify bis(acyl) selenides as key reactive intermediates. Based on our
      findings, we prepare a series of bis(acyl) selenides that provide useful
      precursors with tailored reactivity for liquid-phase syntheses of nanoplatelets.

PMID- 30277488
TI  - Potential models for the simulation of methane adsorption on graphene:
      development and CCSD(T) benchmarks.
AB  - Different force fields for the graphene-CH4 system are proposed including pseudo
      atom and full atomistic models. Furthermore, different charge schemes are tested
      to evaluate the electrostatic interaction for the CH4 dimer. The interaction
      parameters are optimized by fitting to interaction energies at the DFT level,
      which were themselves benchmarked against CCSD(T) calculations. The potentials
      obtained with both the pseudo-atom and full atomistic approaches describe
      accurately enough the average interaction in the methane dimer as well as in the
      graphene-methane system. Moreover, the atom-atom potentials also correctly
      provide the energies associated with different orientations of the molecules. In
      the atomistic models, charge schemes including small charges allow for the
      adequate representation of the stability sequence of significant conformations of
      the methane dimer. Additionally, an intermediate charge of -0.63e on the carbon
      atom in methane leads to bond energies with errors of ca. 0.07 kcal mol-1 with
      respect to the CCSD(T) values for the methane dimer. For the graphene-methane
      interaction, the atom-atom potential model predicts an average interaction energy
      of 2.89 kcal mol-1, comparable to the experimental interaction energy of 3.00
      kcal mol-1. Finally, the presented force fields were used to obtain self
      diffusion coefficients that were checked against the experimental value found in
      the literature. The no-charge and Hirshfeld charge atom-atom models perform
      extremely well in this respect, while the cheapest potential considered, a pseudo
      atom model without charges, still performs reasonably well.

PMID- 30277489
TI  - Antimicrobial glycoconjugate vaccines: an overview of classic and modern
      approaches for protein modification.
AB  - Glycoconjugate vaccines obtained by chemical linkage of a carbohydrate antigen to
      a protein are part of routine vaccinations in many countries. Licensed
      antimicrobial glycan-protein conjugate vaccines are obtained by random
      conjugation of native or sized polysaccharides to lysine, aspartic or glutamic
      amino acid residues that are generally abundantly exposed on the protein surface.
      In the last few years, the structural approaches for the definition of the
      polysaccharide portion (epitope) responsible for the immunological activity has
      shown potential to aid a deeper understanding of the mode of action of
      glycoconjugates and to lead to the rational design of more efficacious and safer
      vaccines. The combination of technologies to obtain more defined carbohydrate
      antigens of higher purity and novel approaches for protein modification has a
      fundamental role. In particular, methods for site selective glycoconjugation like
      chemical or enzymatic modification of specific amino acid residues, incorporation
      of unnatural amino acids and glycoengineering, are rapidly evolving. Here we
      discuss the state of the art of protein engineering with carbohydrates to obtain
      glycococonjugates vaccines and future perspectives.

PMID- 30277490
TI  - MOF-derived Mn doped porous CoP nanosheets as efficient and stable bifunctional
      electrocatalysts for water splitting.
AB  - Searching for highly active and stable bifunctional electrocatalysts for overall
      water splitting, e.g., for both the hydrogen evolution reaction (HER) and the
      oxygen evolution reaction (OER), is dominating in terms of bringing future
      renewable energy storage and conversion processes to reality. In this work, a
      kind of two-dimensional ultrathin manganese (Mn) doped polyhedral cobalt
      phosphide (Mn-CoP) has been synthesized via the etching-carbonization
      phosphidation of Co-centered metal-organic frameworks. The as-prepared porous Mn
      CoP nanosheets had a larger specific surface area and higher porosity, furnishing
      them with more plentiful catalytically active sites than their counterpart hollow
      CoP and Mn-CoP nanoparticles, and thus showed much better electrocatalytic
      activity for both HER and OER in acidic and alkaline media. In addition, the Mn
      CoP nanosheets also demonstrated excellent durability after long-term operation.
      These high performances are attributed to the synergistic effects of the CoP
      nanosheets with intrinsic activity, the graphitic carbon and the controllable
      electronic structure doped by Mn and N elements. This synthetic methodology of
      using a classical MOF as a precursor to build a new 2D sheet-like composite may
      create opportunities to search for highly efficient and robust non-precious metal
      catalysts for energy-related reactions.

PMID- 30277491
TI  - Understanding the role of extracts from sea buckthorn seed residues in anti
      melanogenesis properties on B16F10 melanoma cells.
AB  - The hydroalcoholic extract of sea buckthorn (Hippophae rhamnoides L.) seed
      residues (HYD-SBSR) is a potential skin whitening agent. To test this material as
      a potential skin whitening agent, we identified and quantified the main chemical
      constituents of HYD-SBSR by using ultra-performance liquid chromatography coupled
      with quadruple time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) and
      ultra-high performance liquid chromatography coupled with triple quadruple mass
      spectrometry (UPLC-QQQ-MS). The anti-melanogenesis properties of HYD-SBSR on
      B16F10 mouse melanoma cells were analysed and the mechanism was measured on both
      the transcriptional and translational levels. About 24 compounds were identified.
      Kaempferol and its derivatives were the main compounds with a concentration of
      about (2796.22 +/- 31.55) MUg per g DW. The following order among the detected
      compounds was observed: quercetin and its derivatives > isorhamnetin and its
      derivatives > procyanidins. HYD-SBSR has a strong antioxidant activity but with a
      slight cytotoxic effect on B16F10 when treated with 45.45 MUg mL-1 and 4.55 MUg
      mL-1 respectively, for 48 h. HYD-SBSR has been found to significantly decrease
      melanin content (P < 0.01) in 24 h, 48 h, and 72 h. Additionally, strong
      inhibitory extracellular tyrosinase activities and decreasing intracellular
      tyrosinase activities were also observed (P < 0.01). HYD-SBSR shows inhibitory
      effects on the expression of tyrosinase (TYR) and tyrosinase-related protein 1
      (TRP-1), and the secretion of TYR and TRP-1 proteins in cell lines. The protein
      levels of tyrosinase-related protein 2 (TRP-2) and microphthalmia-associated
      transcription factor (MITF) showed no significant difference. HYD-SBSR may
      inhibit melanin synthesis by decreasing the tyrosinase activity and down
      regulating the expression of TYR and TRP-1 which were probably induced by other
      transcriptional factors rather than MITF.

PMID- 30277493
TI  - An interview with Dr Karen Schindler.

PMID- 30277494
TI  - Xanthine oxidase inhibitor, febuxostat ameliorates the high salt intake-induced
      cardiac hypertrophy and fibrosis in Dahl salt-sensitive rats.
AB  - BACKGROUND: Xanthine oxidase (XO) is a source of reactive oxygen species
      production in the heart. However, pathophysiological role of XO has not been
      clarified in hypertensive heart disease. Thus, the present study examined impacts
      of high salt (HS) intake and febuxostat (Fx), a XO inhibitor in Dahl salt
      sensitive (Dahl-S) rats. METHODS: 8-week old, male Dahl-S rats were fed a normal
      salt diet (0.6% NaCl) or a HS diet (8% NaCl) for 8 weeks. A part of the rats fed
      the HS diet were simultaneously treated with Fx (3mg/kg/day). RESULTS: HS intake
      increased blood pressure and heart weight with cardiomyocyte hypertrophy and
      interstitial fibrosis in the left ventricle (LV), and Fx diminished them. HS
      increased the XO activity 4.7-fold and NADPH oxidase activity 1.5-fold, and Fx
      not only blocked the XO activity but also inhibited the HS-increased nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase activity. HS increased the
      expression of XO, collagen, transforming growth factor-beta1 (TGF-beta1),
      angiotensin-converting enzyme and angiotensin II type 1 receptor and the
      phosphorylation of extracellular signal-regulated kinase (ERK) in the LV, and Fx
      reduced the expression and phosphorylation of these proteins except XO.
      CONCLUSIONS: Fx ameliorates the HS intake-induced hypertension, LV hypertrophy
      and fibrosis with decreasing the TGF-beta1 expression and ERK phosphorylation in
      Dahl-S rats. Fx also down-regulates cardiac NADPH oxidase and renin-angiotensin
      system. The XO inhibition may be an effective therapy for hypertensive heart
      disease.

PMID- 30277492
TI  - Protein mass spectrometry extends temporal blood meal detection over polymerase
      chain reaction in mouse-fed Chagas disease vectors.
AB  - BACKGROUND: Chagas disease is highly prevalent in Latin America, and vector
      control is the most effective control strategy to date. We have previously shown
      that liquid chromatography tandem mass spectrometry (LC-MS/MS) is a valuable tool
      for identifying triatomine vector blood meals. OBJECTIVES: The purpose of this
      study was to determine blood meal detection ability as a function of method
      [polymerase chain reaction (PCR) vs. LC-MS/MS], time since feeding, and the
      effect of molting in mouse-fed triatomine insect vectors targeting hemoglobin and
      albumin proteins with LC-MS/MS and short interspersed nuclear elements (SINE)
      based PCR. METHODS: We experimentally fed Triatoma protracta on mice and used LC
      MS/MS to detect hemoglobin and albumin peptides over time post-feeding and post
      molting (<= 12 weeks). We compared LC-MS/MS results with those of a standard PCR
      method based on SINEs. FINDINGS: Hemoglobin-based LC-MS/MS detected blood meals
      most robustly at all time points post-feeding. Post-molting, no blood meals were
      detected with PCR, whereas LC-MS/MS detected mouse hemoglobin and albumin up to
      12 weeks. MAIN CONCLUSIONS : In our study, the hemoglobin signature in the insect
      abdomen lasted longer than that of albumin and DNA. LC-MS/MS using hemoglobin
      shows promise for identifying triatomine blood meals over long temporal scales
      and even post-molting. Clarifying the frequency of blood-feeding on different
      hosts can foster our understanding of vector behavior and may help devise sounder
      disease-control strategies, including Ecohealth (community based ecosystem
      management) approaches.

PMID- 30277495
TI  - Tenascin-x in Amniotic Fluid and Reproductive Tissues of Pregnancies Complicated
      by Infection and Preterm Prelabor Rupture of Membranes.
AB  - Preterm prelabor rupture of membranes (PPROM), which can precede or follow intra
      amniotic infection/inflammation (IAI) is a poorly understood pregnancy
      complication. Tenascin-X (TNX) is a connective tissue extracellular matrix
      protein that regulates fibrillogenesis of collagens I, III and V. Our goal was to
      investigate the presence and level of soluble TNX (sTNX) in amniotic fluid (AF)
      and TNX expression in reproductive tissues of pregnancies complicated by PPROM
      and IAI. We prospectively recruited 334 women, pregnant with singletons that had
      a clinically indicated amniocentesis for genetic karyotyping, lung maturity
      testing, and rule-out IAI in the presence or absence of PPROM. We quantified TNX
      expression in fetal membranes, myometrium, cervix, and placenta using
      immunological methods and qRT-PCR. In pregnancies with normal outcomes, AF sTNX
      levels were GA-regulated with lower levels toward term. IAI significantly
      upregulated AF sTNX levels independent of membrane status. AF sTNX levels
      inversely correlated with fetal membranes tenascin XB (TNXB) mRNA level, which
      was significantly downregulated by IAI. Western blotting identified
      characteristic ~75 and ~140 kDa sTNX forms in both AF and fetal membranes. Fetal
      membranes, placenta, and cervix constitutively express TNX with the highest
      abundance in the amnion. Amnion TNX richness is significantly lost in the setting
      of IAI. Our results suggest fetal membranes may be a source of AF sTNX whereby
      protein and mRNA expression seem to be significantly impacted by inflammation
      independent of fetal membrane status. A more thorough understanding of TNX
      changes may be valuable for understanding spontaneous PPROM and to potentially
      develop therapeutic targets.

PMID- 30277496
TI  - Telomere length: lights and shadows on their role in human reproduction.
AB  - Telomeres are repeated DNA sequences whose main function is to preserve genome
      stability, protecting chromosomes ends from shortening caused by progressive loss
      during each cell replication or DNA damage. Telomere length regulation is
      normally achieved by telomerase enzyme, whose activity is progressively shut off
      during embryonic differentiation in somatic tissues, whereas it is maintained in
      germ cells, activated lymphocytes, and certain types of stem cell populations.
      The maintenance of telomerase activity for a longer time is necessary for germ
      cells to delay telomere erosion, avoiding thus chromosome segregation defects
      that could contribute to aneuploid or unbalanced gametes. Over the last few
      years, telomere biology has become an important topic in the field of human
      reproduction, encouraging several studies to focus on the relation between
      telomere length and spermatogenesis and male fertility, embryo development and
      quality during assisted reproductive treatment, and female pathologies as
      polycystic ovary, premature ovarian insufficiency and endometriosis. This review
      analyses whether telomere length in germ cells is related to reproduction
      fitness, whether telomere length is related to pathologies associated with male
      and female fertility and whether measurement of telomere length could represent a
      biomarker of germ cell and embryo quality. Telomere length could be considered a
      molecular marker of spermatogenesis and sperm quality and is somewhat related to
      male fertility potential. Fewer evidence, although promising, is available for
      oocytes, female (in)fertility and embryo quality. The increasing evidence for a
      role of telomeres and telomere length in human reproduction, indeed, has expanded
      the historical view of considering them just a marker of aging. Telomere length
      might have in the future a prognostic potential in couple infertility, especially
      useful to select best germ cells with the greatest potential of fertilization.

PMID- 30277497
TI  - E2beta Stimulates Ovine Uterine Artery Endothelial Cell H2S Production in vitro
      by ER-dependent Upregulation of CBS and CTH Expression.
AB  - Endogenous hydrogen sulfide (H2S) is a potent vasodilator and proangiogenic
      second messenger synthesized from L-cysteine by cystathionine beta-synthase (CBS)
      and cystathionine gamma-lyase (CTH). Estrogens are potent vasodilators that
      stimulate H2S biosynthesis in uterine arteries (UA) in vivo; however, the
      underlying mechanisms are unknown. We hypothesized that estrogens stimulate H2S
      biosynthesis in UA endothelial cells (UAEC) via specific estrogen receptor (ER)
      dependent mechanisms. In cultured primary UAEC, treatment with estradiol-17beta
      (E2beta) stimulated CBS and CTH mRNAs and proteins in a time- and concentration-
      dependent fashion. As little as 0.1 nM E2beta was effective in increasing CBS and
      CTH expressions and these stimulatory effects maximized with 10-100 nM E2beta at
      48-72 h. E2beta also activated CBS and CTH promoters in UAEC, leading to CBS and
      CTH expression. Treatment with E2beta stimulated H2S production, which was
      blocked by specific inhibitors of either CBS or CTH and their combination and the
      ER antagonist ICI 182, 780. Treatment with either specific agonist of ERalpha or
      ERbeta stimulated both CBS and CTH mRNA and protein expressions and H2S
      production to levels similar to that of E2beta. Specific antagonist of either
      ERalpha or ERbeta blocked E2beta-stimulated CBS and CTH mRNA and protein
      expressions and H2S production. Combinations of either ERalpha or ERbeta agonists
      or their antagonists had no additive effects. Thus, E2beta stimulates H2S
      production by upregulating CBS and CTH mRNA and protein expressions through
      specific ERalpha or ERbeta dependent CBS and CTH transcription in UAEC in vitro.

PMID- 30277498
TI  - PiGx: reproducible genomics analysis pipelines with GNU Guix.
AB  - In bioinformatics, as well as other computationally intensive research fields,
      there is a need for workflows that can reliably produce consistent output, from
      known sources, independent of the software environment or configuration settings
      of the machine on which they are executed. Indeed, this is essential for
      controlled comparison between different observations and for the wider
      dissemination of workflows. However, providing this type of reproducibility and
      traceability is often complicated by the need to accommodate the myriad
      dependencies included in a larger body of software, each of which generally comes
      in various versions. Moreover, in many fields (bioinformatics being a prime
      example), these versions are subject to continual change due to rapidly evolving
      technologies, further complicating problems related to reproducibility. Here, we
      propose a principled approach for building analysis pipelines and managing their
      dependencies with GNU Guix. As a case study to demonstrate the utility of our
      approach, we present a set of highly reproducible pipelines called PiGx for the
      analysis of RNA sequencing, chromatin immunoprecipitation sequencing, bisulfite
      treated DNA sequencing, and single-cell resolution RNA sequencing. All pipelines
      process raw experimental data and generate reports containing publication-ready
      plots and figures, with interactive report elements and standard observables.
      Users may install these highly reproducible packages and apply them to their own
      datasets without any special computational expertise beyond the use of the
      command line. We hope such a toolkit will provide immediate benefit to laboratory
      workers wishing to process their own datasets or bioinformaticians seeking to
      automate all, or parts of, their analyses. In the long term, we hope our approach
      to reproducibility will serve as a blueprint for reproducible workflows in other
      areas. Our pipelines, along with their corresponding documentation and sample
      reports, are available at http://bioinformatics.mdc-berlin.de/pigx.

PMID- 30277500
TI  - Six-monthly versus annual influenza vaccination in older adults in the tropics:
      an observer-blind, active-comparator controlled, randomised superiority trial.
AB  - Background: Antibody titres and vaccine effectiveness decline within six months
      after influenza vaccination in older adults. Biannual vaccination may be
      necessary to provide year-round protection in the tropics where influenza
      circulates throughout the year. Methods: Tropical Influenza Control Strategies
      (TROPICS1) was a single-centre, 1:1 randomised, observer-blinded, active
      comparator controlled, superiority study in 200 community-resident adults aged
      >=65 years. Participants received standard-dose trivalent inactivated influenza
      vaccination (IIV3) at enrolment, and either tetanus-diphtheria-pertussis
      vaccination or IIV3 six months later. Primary outcome was the proportion of
      participants with haemagglutination-inhibition (HI) geometric mean titre (GMT)
      >=1:40 one month after the second vaccination (Month 7). Secondary outcomes
      included GMTs to Month 12, the incidence of influenza-like illness (ILI), and
      adverse reactions after vaccination. Results: At Month 7, the proportion of
      participants with a HI tire >=1:40 against A/H1N1 increased by 21.4% (95% CI 8.6
      33.4) in the six-monthly vaccination group. This proportion was not significantly
      higher for A/H3N2 (4.3, 95% CI -1.1-10.8) or B (2.1, 95% CI -2.0-7.3). Six
      monthly vaccination significantly increased GMTs against A/H1N1 and A/H3N2 at
      Month 7, but not B. Participants receiving repeat IIV3 reported a significantly
      lower incidence of ILI in the six months after the second vaccination (relative
      vaccine effectiveness 57.1%, 95% CI 0.6-81.5). The frequency of adverse events
      was similar after first or second influenza vaccination.

PMID- 30277502
TI  - Radiotherapy improves the survival of patients with metastatic esophageal
      squamous cell carcinoma: a propensity score matched analysis of Surveillance,
      Epidemiology, and End Results database.
AB  - The survival advantage of radiotherapy (RT) for patients with metastatic
      esophagus cancer has not been adequately evaluated. This study aims to find out
      the role of RT for metastatic esophagus cancer and to find the different effect
      for RT to esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma
      (ESCC). This study included 5,970 metastatic esophagus cancer patients from the
      Surveillance, Epidemiology, and End Results (SEER) database, registered from
      January 2004 to December 2013. Propensity score (PS) analysis with 1:1 nearest
      neighbor matching method was used to ensure well-balanced characteristics of all
      comparison groups by histological types. The Kaplan-Meier and Cox proportional
      hazardous models were used to evaluate the overall survival (OS), cancer-specific
      survival (CSS), and corresponding 95% confidence interval (CI). Generally
      speaking, EAC did not get survival benefit from RT (median OS for RT group vs. no
      RT group-8.0, 7.6-8.4 vs. 9.0, 8.5-9.5, P = 0.073), whereas RT for metastatic
      ESCC did significantly improve OS (median OS for RT group vs. no-RT group-8.0,
      7.4-8.6 vs. 7.0, 6.4-7.6, P = 0.044). Therefore, compared with adenocarcinoma,
      ESCC could get more survival benefit from RT.

PMID- 30277503
TI  - Bt Resistance Implications for Helicoverpa zea (Lepidoptera: Noctuidae)
      Insecticide Resistance Management in the United States.
AB  - Both maize and cotton genetically engineered to express Bt toxins are widely
      planted and important pest management tools in the United States. Recently,
      Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) has developed resistance to two
      toxin Bt maize and cotton (Cry1A and Cry2A). Hence, growers are transitioning to
      three toxin Bt cotton and maize that express both Cry toxins and the Vip3Aa
      toxin. H. zea susceptibility to Vip3Aa is threatened by 1) a lack of availability
      of non-Bt refuge crop hosts, including a 1-5% annual decline in the number of non
      Bt maize hybrids being marketed; 2) the ineffectiveness of three toxin cultivars
      to function as pyramids in some regions, with resistance to two out of three
      toxins in the pyramid; and 3) the lack of a high dose Vip3Aa event in cotton and
      maize. We propose that data should be collected on current Cry-resistant H. zea
      in the field to inform future Bt resistance models and that the deployment of Bt
      toxins and non-Bt refuge crops should be adjusted to favor susceptibility of H.
      zea to Bt toxins such as Vip3Aa. Finally, maize growers should be incentivized to
      plant non-Bt structured refuge and have access to hybrids with high-yielding
      genetic potential at a reasonable price.

PMID- 30277499
TI  - MetaPGN: a pipeline for construction and graphical visualization of annotated
      pangenome networks.
AB  - Pangenome analyses facilitate the interpretation of genetic diversity and
      evolutionary history of a taxon. However, there is an urgent and unmet need to
      develop new tools for advanced pangenome construction and visualization,
      especially for metagenomic data. Here, we present an integrated pipeline, named
      MetaPGN, for construction and graphical visualization of pangenome networks from
      either microbial genomes or metagenomes. Given either isolated genomes or
      metagenomic assemblies coupled with a reference genome of the targeted taxon,
      MetaPGN generates a pangenome in a topological network, consisting of genes
      (nodes) and gene-gene genomic adjacencies (edges) of which biological information
      can be easily updated and retrieved. MetaPGN also includes a self-developed
      Cytoscape plugin for layout of and interaction with the resulting pangenome
      network, providing an intuitive and interactive interface for full exploration of
      genetic diversity. We demonstrate the utility of MetaPGN by constructing
      Escherichia coli pangenome networks from five E. coli pathogenic strains and 760
      human gut microbiomes,revealing extensive genetic diversity of E. coli within
      both isolates and gut microbial populations. With the ability to extract and
      visualize gene contents and gene-gene physical adjacencies of a specific taxon
      from large-scale metagenomic data, MetaPGN provides advantages in expanding
      pangenome analysis to uncultured microbial taxa.

PMID- 30277501
TI  - ESR2 Is Essential for Gonadotropin-Induced Kiss1 Expression in Granulosa Cells.
AB  - Hypothalamic expression of Kiss1 plays an essential role in the onset of puberty,
      gonadal development, and ovulation. Estrogens regulate the expression of Kiss1 in
      the hypothalamus through estrogen receptor-alpha. Kiss1 is also expressed in the
      ovary, where its expression correlates with the onset of puberty and progression
      of the estrous cycle. To date, estrogen regulation of Kiss1 expression in the
      ovary has not been investigated. We recently observed that gonadotropin-induced
      Kiss1 expression was absent in Esr2-null rat ovaries even though Esr1 was
      present. Wild-type granulosa cells abundantly expressed Kiss1 and oocytes
      expressed the Kiss1 receptor. We characterized estrogen receptor-beta (ESR2)
      regulation of Kiss1 expression in granulosa cells by identifying granulosa cell
      specific transcript variants and potential regulatory regions. The Kiss1
      promoter, an upstream enhancer, and a downstream enhancer all possessed conserved
      estrogen response elements (EREs) and showed active histone marks in gonadotropin
      stimulated granulosa cells. The transcriptionally active Kiss1 promoter, as well
      as the enhancers, also revealed enrichment for ESR2 binding. Furthermore,
      activity of a Kiss1 promoter construct was induced after overexpression of ESR2
      and was blocked upon mutation of an ERE within the promoter. Finally, pregnant
      mare serum gonadotropin and human chorionic gonadotropin administration induced
      phosphorylation of ESR2 and upregulated the AP-1 proteins FOSL2 and JUNB in
      granulosa cells. Activated MAPK ERK2 was associated with the ESR2 phosphorylation
      in granulosa cells, and AP-1 factors could synergistically activate the Kiss1
      promoter activity. These gonadotropin-induced changes paralleled Kiss1 expression
      in granulosa cells. We conclude that gonadotropin-stimulated Kiss1 expression in
      granulosa cells is dependent on both the activation of ESR2 and the upregulation
      of AP-1.

PMID- 30277506
TI  - Ectoparasitic Mites Varroa underwoodi (Acarina: Varroidae) in Eastern Honeybees,
      but not in Western Honeybees.
AB  - The ectoparasitic mite Varroa destructor Anderson and Trueman (Acarina:
      Varroidae) shifted host from Eastern honeybees Apis cerana Fabricius
      (Hymenoptera: Apidae) to Western honeybees Apis mellifera Linnaeus (Hymenoptera:
      Apidae) with disastrous consequences globally. The high genetic diversity of V.
      destructor and abundant opportunities for cross-species transmission probably
      promoted this host shift. Whether Varroa underwoodi (Acarina: Varroidae) also
      exhibits these traits is unknown. Here, we conduct a large-scale survey across
      China on the occurrence, morphology, reproduction, and genetics of V. underwoodi
      in A. cerana and A. mellifera colonies to fill gaps in our knowledge of this mite
      and to determine whether host shifts occurred. Despite the large number of
      colonies screened, V. underwoodi was exclusively found in A. cerana, where it
      occurred at low infestation rates. Three genetic clades were detected in the V.
      underwoodi population, which differed neither in morphology nor in reproductive
      ability. Nevertheless, the genetic diversity of V. underwoodi is likely to
      increase chances for host shifts, even though opportunities for cross-species
      transmission seem low. More studies of the neglected Varroa species seem
      appropriate to enable a better understanding of host shifts in the Apis
      spp./Varroa spp. system and evaluate the potential risk they pose to apiculture
      with A. mellifera.

PMID- 30277504
TI  - Expression profile of miR-17/92 cluster is predictive of treatment response in
      rectal cancer.
AB  - MicroRNA (miRNA) profiling represents a promising source of cancer-related
      biomarkers. miRNA signatures are specific for each cancer type and subgroups of
      patients with diverse treatment sensitivity. Yet this miRNA potential has not
      been satisfactorily explored in rectal cancer (RC). The aim of the study was to
      identify the specific miRNA signature with clinical and therapeutic relevance for
      RC. Expressions of 2555 miRNA were examined in 20 pairs of rectal tumors and
      matched non-malignant tissues by 3D-Gene Toray microarray. Candidate miRNAs were
      validated in an independent cohort of 100 paired rectal tissues and in whole
      plasma and exosomes of 100 RC patients. To study the association of miRNA profile
      with therapeutic outcomes, plasma samples were taken repeatedly over a time
      period of 1 year reflecting thus patients' treatment responses. Finally, the most
      prominent miRNAs were investigated in vitro for their involvement in cell growth.
      We identified RC-specific miRNA signature that distinguishes responders from non
      responders to adjuvant chemotherapy. A predominant part of identified miRNAs was
      represented by the members of miR-17/92 cluster. Upregulation of miRNA-17, -18a, 
      18b, -19a, -19b, -20a, -20b and -106a in tumor was associated with higher risk of
      tumor relapse and their overexpression in RC cell lines stimulated cellular
      proliferation. Examination of these miRNAs in plasma exosomes showed that their
      levels differed between RC patients and healthy controls and correlated with
      patient's treatment response. miRNAs from miR-17/92 cluster represent a non
      invasive biomarker to predict posttreatment prognosis in RC patients.

PMID- 30277505
TI  - Emerging resistance to empiric antimicrobial regimens for pediatric bloodstream
      infections in Malawi (1998-2017).
AB  - Background: The adequacy of the WHO Integrated Management of Childhood Illness
      (IMCI) antimicrobial guidelines for the treatment of suspected severe bacterial
      infections is dependent on a low prevalence of antimicrobial resistance (AMR). We
      describe trends in etiologies and susceptibility patterns of bloodstream
      infections (BSI) in hospitalized children in Malawi. Methods: We determined the
      change in population-based incidence of BSI in children admitted to Queen
      Elizabeth Central Hospital, Blantyre, Malawi (1998-2017). AMR profiles were
      assessed by the disc diffusion method and trends over time were evaluated.
      Results: A total 89,643 pediatric blood cultures were performed, and 10,621
      pathogens were included in the analysis. Estimated minimum incidence rates of BSI
      for those <=5 years of age fell from a peak of 11.4 per 1,000 persons in 2002 to
      3.4 per 1,000 persons in 2017. Over two decades, resistance of Gram-negative
      pathogens to all empiric first-line antimicrobials (ampicillin/penicillin,
      gentamicin, ceftriaxone) among children <=5 years increased from 3.4% to 30.2%
      (p<0.001). Among those <=60 days, AMR to all first-line antimicrobials increased
      from 7.0% to 67.7% (p<0.001). Among children <=5 years, Klebsiella spp.
      resistance to all first-line antimicrobial regimens increased from 5.9% to 93.7%
      (p<0.001). Conclusions: The incidence of BSI among hospitalized children has
      decreased substantially over the last 20 years, although gains have been offset
      by increases in Gram-negative pathogens resistant to all empiric first-line
      antimicrobials. There is an urgent need to address the broader challenge of
      adapting IMCI guidelines to the local setting in the face of rapidly expanding
      AMR in childhood BSI.

PMID- 30277507
TI  - Patient cardiovascular risk self-management: results from a randomized trial of
      motivational interviewing delivered by practice nurses.
AB  - Background: To enhance cardiovascular risk management and patients' self
      management, a tailored programme to improve cardiovascular risk management was
      tested in a randomized trial. The presented study concerned secondary analysis.
      Objectives: To explore the correlations of practice nurses' counselling skills at
      baseline on chronic illness care (measured with Patient Assessment of Chronic
      Illness Care questionnaire) and patients' self-management (assessed with Patient
      Activation Measure) at follow-up and to examine the effect of the tailored
      implementation programme on chronic illness care and patients' self-management.
      Methods: A two-arm cluster randomized trial was conducted in 34 general practices
      in the Netherlands. Counselling skills of practice nurses at baseline were
      abstracted from audio-taped consultations, which were assessed by Motivational
      Interviewing Treatment Integrity. Data of 2184 patients with established
      cardiovascular disease or at high cardiovascular risk were gathered at inclusion
      and at 6 months follow-up by a composite questionnaire. Multilevel regression
      analysis was applied, controlling for patient characteristics. Results:
      Counselling skills of practice nurses were not associated with chronic illness
      care and patients' self-management scores. At follow-up, patients in the
      intervention group experienced less chronic illness care and were less activated
      in disease management than patients in the control group. The most important
      predictors were patients' age, gender and education level. Conclusions: The logic
      model underlying the implementation programme needs to be reconsidered, because
      patient perceptions were neither influenced by nurses' counselling skills nor by
      other components of the implementation programme.

PMID- 30277508
TI  - Correction.

PMID- 30277509
TI  - The Insecticide Resistance Allele kdr-his has a Fitness Cost in the Absence of
      Insecticide Exposure.
AB  - House flies, Musca domestica L. (Diptera: Muscidae), are major pests at animal
      production facilities. Insecticides, particularly pyrethroids, have been used for
      control of house fly populations for more than 30 yr, but the evolution of
      resistance will likely jeopardize fly control efforts. A major mechanism of
      pyrethroid resistance in the house fly is target site insensitivity (due to
      mutations in the Voltage-sensitive sodium channel [Vssc]). Based on a survey of
      house fly populations in 2007 and 2008, the most common resistance allele at 2/3
      of the states in the United States is kdr-his. This was unexpected given the
      relatively lower level of resistance this allele confers, and led to speculation
      that the kdr-his allele may have a minimal fitness cost in the absence of
      insecticide. The goal of this study was to evaluate the fitness cost of kdr-his
      by monitoring the changes in allele frequency over 15 generations in the absence
      of insecticide. In crosses with two different insecticide susceptible strains, we
      found that kdr-his had a significant fitness cost. The implications of these
      results to insecticide resistance monitoring and management are discussed.

PMID- 30277510
TI  - Editorial for Liver Cancer in Asia.

PMID- 30277512
TI  - Impact of Insecticide Seed Treatments and Foliar Insecticides on Aphid
      Infestations in Wheat, Incidence of Barley Yellow Dwarf, and Yield in West
      Tennessee.
AB  - Several species of aphids (Hemiptera: Aphididae) infesting wheat may reduce yield
      by the transmission of barley yellow dwarf (BYD). Neonicotinoid seed treatments
      and foliar application of insecticides are two common methods to control aphid
      infestations and reduce BYD. An analysis was carried out across 33 insecticide
      efficacy tests performed in west Tennessee during the last 11 yr to determine how
      insecticide seed treatments and/or a late-winter foliar insecticide application
      affected aphid populations, incidence of BYD, and yield. A significant decrease
      in springtime aphid populations and incidence of BYD was observed when using a
      seed treatment, a foliar insecticide application, or both. Average wheat yields
      were increased by 280-381 kg/ha (5.3-7.2%) if an insecticide seed treatment was
      used or when a foliar insecticide application was made. Compared with insecticide
      seed treatments, average springtime aphid populations and the incidence of BYD
      were lower when a foliar insecticide was applied. A foliar insecticide
      application made in addition to insecticide seed treatments increased yield by an
      average of 196 kg/ha (3.4%). The yield increases over the nontreated control
      suggest that wheat growers in west Tennessee can use insecticides to manage
      aphids and prevent transmission of BYD. Consideration of environmental
      conditions, whether or not insecticide seed treatments were used, and scouting
      can be used to help make decisions on when or if to apply foliar insecticides.

PMID- 30277511
TI  - Enteric Fever Cases in the Two Largest Pediatric Hospitals of Bangladesh: 2013
      2014.
AB  - Background: Enteric fever predominantly affects children in low- and middle
      income countries. This study examines the burden of enteric fever at the 2
      pediatric hospitals in Dhaka, Bangladesh and assesses their capacity for
      inclusion in a prospective cohort study to support enteric fever prevention and
      control. Methods: A descriptive study of enteric fever was conducted among
      children admitted in 2013-2014 to inpatient departments of Dhaka Shishu and
      Shishu Shashthya Foundation Hospitals, sentinel hospitals of the World Health
      Organization-supported Invasive Bacterial Vaccine Preventable Disease
      surveillance platform. Results: Of 15917 children with blood specimens received
      by laboratories, 2.8% (443 of 15917) were culture positive for significant
      bacterial growth. Sixty-three percent (279 of 443) of these isolates were
      confirmed as the cases of enteric fever (241 Salmonella Typhi and 38 Salmonella
      Paratyphi A). In addition, 1591 children had suspected enteric fever. Overall,
      3.6% (1870 of 51923) were laboratory confirmed or suspected enteric fever cases
      (55% male, median age 2 years, 86% from Dhaka district, median hospital stay 5
      days). Conclusions: The burden of enteric fever among inpatients at 2 pediatric
      hospitals in Dhaka, Bangladesh is substantial. Therefore, inclusion of these
      hospitals in a prospective cohort study will be useful for the generation of
      credible disease burden estimates of enteric fever in Bangladesh.

PMID- 30277513
TI  - Neonicotinoid Insecticide Resistance in Tobacco Thrips (Thysanoptera: Thripidae)
      of Mississippi.
AB  - Insecticidal efficacy of neonicotinoid insecticides used against tobacco thrips,
      Frankliniella fusca (Hinds) (Thysanoptera: Thripidae), in cotton, Gossypium
      hirisutum L. (Malvales: Malvaceae), was evaluated for field populations collected
      in Mississippi during 2014-2016. Resistance was documented in 16 and 57% of
      populations to imidacloprid and thiamethoxam, respectively. Resistance levels did
      not vary by host plant for any neonicotinoid, but resistance levels varied
      between the two main agricultural areas (Delta and Hills) of Mississippi and
      among years for some neonicotinoids. In spite of documented resistance,
      neonicotinoid seed treatments are still used on cotton in the midsouthern United
      States due to the lack of reliable alternative management strategies. The
      development of alternative thrips management strategies is critical to the
      sustainability of cotton production in the midsouthern United States.

PMID- 30277514
TI  - Exercise for physical fitness, fatigue and quality of life of patients undergoing
      hematopoietic stem cell transplantation: a meta-analysis of randomized controlled
      trials.
AB  - Objectives: The objective of this meta-analysis is to systematically review the
      evidence on effects of exercise interventions in comparison to usual care with
      respect to physical fitness, fatigue, quality of life, anxiety and depression in
      hematopoietic stem cell transplantation patients for a hematological
      malignancies. And we are more focused on the optimal opportunity to exercise in
      hematopoietic stem cell transplantation recipients. Method: Databases were
      searched up to June 2018. We included randomized controlled trials comparing
      exercise with usual care in adult patients who had a hematologic malignancy.
      Standard mean differences were calculated and pooled to generate summary effect
      sizes and 95% confidence intervals. The Cochrane Collaboration Risk of Bias Tool
      was used to assess the methodological quality of the studies. Results: This meta
      analysis showed that exercise had a positive effect on lower muscle strength,
      fatigue and quality of life and had no effects on patients' cardiorespiratory
      fitness, upper muscle strength, psychosocial fitness and adverse events. Subgroup
      analysis showed that exercise had a favorable effect on upper/lower muscle
      strength, fatigue and quality of life when starting exercise pre-transplant, but
      exercise had no effects, except on quality of life when starting exercise after
      transplant. And patients in the pre-transplant exercise group did not exercise
      more graft vs host disease events nor deaths. Conclusion: Therefore, we can
      conclude that the optimal timing for the hematopoietic stem cell transplantation
      recipients to begin exercise training is before transplantation.

PMID- 30277515
TI  - psichomics: graphical application for alternative splicing quantification and
      analysis.
AB  - Alternative pre-mRNA splicing generates functionally distinct transcripts from
      the same gene and is involved in the control of multiple cellular processes, with
      its dysregulation being associated with a variety of pathologies. The advent of
      next-generation sequencing has enabled global studies of alternative splicing in
      different physiological and disease contexts. However, current bioinformatics
      tools for alternative splicing analysis from RNA-seq data are not user-friendly,
      disregard available exon-exon junction quantification or have limited downstream
      analysis features. To overcome such limitations, we have developed psichomics, an
      R package with an intuitive graphical interface for alternative splicing
      quantification and downstream dimensionality reduction, differential splicing and
      gene expression and survival analyses based on The Cancer Genome Atlas, the
      Genotype-Tissue Expression project, the Sequence Read Archive project and user
      provided data. These integrative analyses can also incorporate clinical and
      molecular sample-associated features. We successfully used psichomics in a laptop
      to reveal alternative splicing signatures specific to stage I breast cancer and
      associated novel putative prognostic factors.

PMID- 30277516
TI  - Identification of novel protein phosphatases as modifiers of alpha-synuclein
      aggregation in yeast.
AB  - Alpha-synuclein (aSyn) is a key player in a group of neurodegenerative diseases
      commonly known as synucleinopathies. Recent findings indicate phosphorylation in
      several aSyn residues can modulate its aggregation and subcellular localization,
      thereby affecting pathological processes. However, the precise molecular
      mechanisms governing aSyn phosphorylation are still unclear. Recent studies
      investigated the role of various families of protein kinases, such as the polo
      like kinases, G protein-coupled receptor kinases or casein kinases. In contrast,
      our understanding of the phosphatases involved in the dephosphorylation of aSyn
      is rather limited. Here, we exploited the unique toolbox of the yeast
      Saccharomyces cerevisiae in order to identify novel phosphatases capable of
      modulating aSyn phosphorylation, inclusion formation and toxicity of human aSyn.
      In summary, given the association between aSyn phosphorylation and pathology in
      Parkinson's disease and other synucleinopathies, modulation of this post
      translational modification may constitute an attractive target for therapeutic
      intervention.

PMID- 30277517
TI  - Environmental dimensions of antibiotic resistance: assessment of basic science
      gaps.
AB  - Antibiotic resistance is one of the major problems facing medical practice in the
      21st century. Historical approaches to managing antibiotic resistance have often
      focused on individual patients, specific pathogens and particular resistance
      phenotypes. However, it is increasingly recognized that antibiotic resistance is
      a complex ecological and evolutionary problem. As such, understanding the
      dynamics of antibiotic resistance requires integration of data on the diverse
      mobile genetic elements often associated with antibiotic resistance genes, and
      their dissemination by various mechanisms of horizontal gene transfer between
      bacterial cells and environments. Most important is understanding the fate and
      effects of antibiotics at sub-inhibitory concentrations, and co-selection. This
      opinion paper identifies key knowledge gaps in our understanding of resistance
      phenomena, and outlines research needs that should be addressed to help us manage
      resistance into the future.

PMID- 30277518
TI  - The role of yeast ARO8, ARO9 and ARO10 genes in the biosynthesis of 3
      (methylthio)-1-propanol from L-methionine during fermentation in synthetic grape
      medium.
AB  - 3-(Methylthio)-1-propanol (methionol), produced by yeast as an end-product of L
      methionine (L-Met) catabolism, imparts off-odours reminiscent of cauliflower and
      potato to wine. Saccharomyces cerevisiae ARO genes, including transaminases Aro8p
      and Aro9p, and decarboxylase Aro10p, catalyse two key steps forming methionol via
      the Ehrlich pathway. We compared methionol concentrations in wines fermented by
      single Deltaaro8, Deltaaro9, and Deltaaro10 deletants in lab strain BY4743 versus
      wine strain Zymaflore F15, and F15 double- and triple-aro deletants versus single
      aro deletants, using headspace-solid phase microextraction coupled with gas
      chromatography-mass spectrometry (HS-SPME/GC-MS).Deletion of two or more aro
      genes increased growth lag phase, with the greatest delay exhibited by F15
      Deltaaro8 Deltaaro9. The single Deltaaro8 deletion decreased methionol by 44% in
      BY4743 and 92% in F15, while the Deltaaro9 deletion increased methionol by 46% in
      F15 but not BY4743. Single deletion of Deltaaro10 had no effect on
      methionol.Unexpectedly, F15 Deltaaro8 Deltaaro9 and F15 Deltaaro8 Deltaaro9
      Deltaaro10 produced more methionol than F15 Deltaaro8. In the absence of Aro8p
      and Aro9p, other transaminases may compensate or an alternative pathway may
      convert methanethiol to methionol. Our results confirm that Ehrlich pathway genes
      differ greatly between lab and wine yeast strains, impacting downstream products
      such as methionol.

PMID- 30277519
TI  - Final report of survival and late toxicities in the Phase I study of stereotactic
      body radiation therapy for peripheral T2N0M0 non-small cell lung cancer
      (JCOG0702).
AB  - Purpose: A dose escalation study to determine the recommended dose with
      stereotactic body radiation therapy (SBRT) for peripheral T2N0M0 non-small cell
      carcinomas (JCOG0702) was conducted. The purpose of this paper is to report the
      survival and the late toxicities of JCOG0702. Materials and methods: The
      continual reassessment method was used to determine the dose level that patients
      should be assigned to and to estimate the maximum tolerated dose. The starting
      dose was 40 Gy in four fractions at D95 of PTV. Results: Twenty-eight patients
      were enrolled. Ten patients were treated with 40 Gy at D95 of PTV, four patients
      with 45 Gy, eight patients with 50 Gy, one patient with 55 Gy and five patients
      with 60 Gy. Ten patients were alive at the last follow-up. Overall survival (OS)
      for all patients was 67.9% (95% CI 47.3-81.8%) at 3 years and 40.8% (95% CI 22.4
      58.5%) at 5 years. No Grade 3 or higher toxicity was observed after 181 days from
      the beginning of the SBRT. Compared to the toxicities up to 180 days, chest wall
      related toxicities were more frequent after 181 days. Conclusions: The 5-year OS
      of 40.8% indicates the possibility that SBRT for peripheral T2N0M0 non-small cell
      lung cancer is superior to conventional radiotherapy. The effect of the SBRT dose
      escalation on OS is unclear and further studies are warranted.

PMID- 30277520
TI  - Stacking-induced fluorescence increase reveals allosteric interactions through
      DNA.
AB  - From gene expression to nanotechnology, understanding and controlling DNA
      requires a detailed knowledge of its higher order structure and dynamics. Here we
      take advantage of the environment-sensitive photoisomerization of cyanine dyes to
      probe local and global changes in DNA structure. We report that a covalently
      attached Cy3 dye undergoes strong enhancement of fluorescence intensity and
      lifetime when stacked in a nick, gap or overhang region in duplex DNA. This is
      used to probe hybridization dynamics of a DNA hairpin down to the single-molecule
      level. We also show that varying the position of a single abasic site up to 20
      base pairs away modulates the dye-DNA interaction, indicative of through-backbone
      allosteric interactions. The phenomenon of stacking-induced fluorescence increase
      (SIFI) should find widespread use in the study of the structure, dynamics and
      reactivity of nucleic acids.

PMID- 30277521
TI  - New revisions and current issues in the eighth edition of the TNM classification
      for non-small cell lung cancer.
AB  - In the eighth edition of the TNM classification of lung cancer, the prognostic
      impact of tumor size is emphasized as a descriptor of all T categories.
      Especially in lung cancer where tumor size is 5 cm or less, the 1-cm cutoff point
      significantly differentiated the survival outcome. In addition, the new staging
      categories were assigned, namely, Tis (adenocarcinoma in situ) and T1mi
      (minimally invasive adenocarcinoma). Furthermore, the measurement of a
      radiological solid component size excluding the ground glass opacity component or
      pathological invasive size without a lepidic component was proposed for deciding
      the cT/pT categories for lung adenocarcinoma. The N descriptors were kept the
      same as in the eventh edition on the whole, however, quantification of nodal
      disease had a prognostic impact based on the number of nodal stations involved in
      the eighth edition, i.e. N1a as a single N1 station, N1b as a multiple N1
      station, N2a1 as a single N2 station without N1 (skip metastasis), N2a2 as a
      single N2 station with N1 disease, and N2b as a multiple N2 station. In the M
      descriptors, subclassification was performed based on the location or numbers of
      distantly metastatic lesions, i.e. M1a as any intrathoracic metastases, M1b as a
      single distant metastatic lesion in one organ, and M1c as multiple distant
      metastases in either a single organ or multiple organs. Survival analysis of the
      eighth edition of the TNM classification clearly separated the distinct groups,
      however, unsolved issues still remain that should be discussed and further
      revised for the forthcoming TNM staging system.

PMID- 30277523
TI  - Repellency and Laboratory Performance of Selected Insecticides to Field-Collected
      Insecticide Resistant German Cockroaches (Blattodea: Ectobiidae).
AB  - German cockroaches, Blattella germanica (L.) (Blattodea: Ectobiidae), are
      important indoor insect pests and remain difficult to control because of their
      ability to develop resistance to insecticides. The toxicity, resistance levels,
      repellency, and performance index (PI) value of five formulated insecticides
      (permethrin, chlorpyrifos, propoxur, imidacloprid, and fipronil) were determined
      for adult males of seven strains of the German cockroach: a laboratory-reared
      susceptible strain (S) and six field-collected strains (B, D, E, G, H, and I).
      Propoxur was generally the most toxic insecticide to all strains using continuous
      exposure methods; however, using Ebeling choice box methods, chlorpyrifos, and
      fipronil were most toxic. In both continuous exposure and Ebeling choice box
      tests, the field-collected strains were generally most resistant to permethrin
      among the five insecticides. The greatest increase in resistance ratios between
      the two exposure methods was for permethrin and propoxur. Permethrin was the most
      repellent insecticide against all but two strains (D and H). PI values reached
      100 (no repellency and complete mortality) for the susceptible strain against
      only chlorpyrifos and fipronil. Only fipronil resulted in a PI value of 100 for
      any of the field-collected strains. Continuous exposure and Ebeling choice box
      resistance ratios were correlated, and both were correlated with previously
      reported resistance ratios (based on LD50 values). Choice box repellency,
      however, was only correlated with LD50 resistance ratios. PIMax was negatively
      correlated with all measures of resistance ratios.

PMID- 30277524
TI  - Parental tobacco use and child death: analysis of data from demographic and
      health surveys from South and South East Asian countries.
AB  - Background: Child mortality is a public health challenge in developing countries,
      and exposure to second-hand smoke and prenatal exposure to smokeless tobacco are
      risk factors for child death. We determined the associations between parental
      tobacco use and child death under the age of five in eight South and South East
      Asian countries. Methods: We analysed cross-sectional demographic and health
      survey data collected between 2005 and 2016, using multiple logistic regressions
      to estimate the unadjusted and adjusted associations between parental tobacco use
      and child death, accounting for demographic and economic covariates. Results:
      Overall prevalence of tobacco smoking was 46.8% for fathers and 2.7% for mothers,
      smokeless tobacco use was 32.6% for fathers and 7.8% for mothers and any tobacco
      use was 67.1% for fathers and 10.1% for mothers. Adjusted for demographic and
      economic covariates, child death was significantly associated with fathers' [odds
      ratio: 1.10; 95% confidence interval (CI): 1.03, 1.17] and mothers' (1.44; 1.23,
      1.70) smoking tobacco, fathers' (1.25; 1.17, 1.34) and mothers' (1.11; 1.00,
      1.23) use of smokeless tobacco and fathers' (1.21; 1.13, 1.29) and mothers'
      (1.24; 1.12, 1.36) use of any tobacco. Conclusions: Both smoked tobacco and
      smokeless tobacco policies should be aggressively implemented in public places
      and workplaces in developing countries, because they stimulate voluntary smoke
      and smokeless tobacco-free policies in homes.

PMID- 30277522
TI  - NMR structure of a G-quadruplex formed by four d(G4C2) repeats: insights into
      structural polymorphism.
AB  - Most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and
      frontotemporal dementia (FTD), is a largely increased number of d(G4C2)n*(G2C4)n
      repeats located in the non-coding region of C9orf72 gene. Non-canonical
      structures, including G-quadruplexes, formed within expanded repeats have been
      proposed to drive repeat expansion and pathogenesis of ALS and FTD.
      Oligonucleotide d[(G4C2)3G4], which represents the shortest oligonucleotide model
      of d(G4C2) repeats with the ability to form a unimolecular G-quadruplex, forms
      two major G-quadruplex structures in addition to several minor species which
      coexist in solution with K+ ions. Herein, we used solution-state NMR to determine
      the high-resolution structure of one of the major G-quadruplex species adopted by
      d[(G4C2)3G4]. Structural characterization of the G-quadruplex named AQU was
      facilitated by a single substitution of dG with 8Br-dG at position 21 and
      revealed an antiparallel fold composed of four G-quartets and three lateral C-C
      loops. The G-quadruplex exhibits high thermal stability and is favored
      kinetically and under slightly acidic conditions. An unusual structural element
      distinct from a C-quartet is observed in the structure. Two C*C base pairs are
      stacked on the nearby G-quartet and are involved in a dynamic equilibrium between
      symmetric N3-amino and carbonyl-amino geometries and protonated C+*C state.

PMID- 30277525
TI  - Early life disadvantage and adult adiposity: tests of sensitive periods during
      childhood and behavioural mediation in adulthood.
AB  - Background: Early exposure to socioeconomic disadvantage is associated with
      obesity. Here we investigated how early, and conducted mediation analyses to
      identify behavioural factors in adulthood that could explain why. Methods: Among
      931 participants in the New England Family Study, we investigated the
      associations of family socioeconomic disadvantage measured before birth and at
      age 7 years with the following measures of adiposity in mid-adulthood (mean age =
      44.4 years): body mass index (BMI), waist circumference and, among 400
      participants, body composition from dual-energy X-ray absorption scans. Results:
      In linear regressions adjusting for age, sex, race and childhood BMI Z-score,
      participants in the highest tertile of socioeconomic disadvantage at birth had
      2.6 additional BMI units in adulthood [95% confidence interval (CI) = 1.26,
      3.96], 5.62 cm waist circumference (95% CI = 2.69, 8.55), 0.73 kg of android fat
      mass (95% CI = 0.25, 1.21), and 7.65 higher Fat Mass Index (95% CI = 2.22,
      13.09). Conditional on disadvantage at birth, socioeconomic disadvantage at age 7
      years was not associated with adult adiposity. In mediation analyses, 10-20% of
      these associations were explained by educational attainment and 5-10% were
      explained by depressive symptoms. Conclusions: Infancy may be a sensitive period
      for exposure to socioeconomic disadvantage, as exposure in the earliest years of
      life confers a larger risk for overall and central adiposity in mid-adulthood
      than exposure during childhood. Intervention on these two adult risk factors for
      adiposity would, if all model assumptions were satisfied, only remediate up to
      one-fifth of the excess adult adiposity among individuals born into
      socioeconomically disadvantaged households.

PMID- 30277526
TI  - Loss of MeCP2 in immature neurons leads to impaired network integration.
AB  - Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations or
      deletions in Methyl-CpG-binding Protein 2 (MeCP2), a brain-enriched
      transcriptional regulator. MeCP2 is highly expressed during neuronal maturation
      and its deficiency results in impaired dendritic morphogenesis and reduced
      dendritic spine numbers in developing neurons. However, whether MeCP2 deficiency
      impacts the integration of new neurons has not been directly assessed. In this
      study, we developed a modified rabies virus-mediated monosynaptic retrograde
      tracing method to interrogate presynaptic integration of MeCP2-deficent new
      neurons born in the adult hippocampus, a region with lifelong neurogenesis and
      plasticity. We found that selective deletion of MeCP2 in adult-born new neurons
      impaired their long-range connectivity to the cortex, whereas their connectivity
      within the local hippocampal circuits or with subcortical regions was not
      significantly affected. We further showed that knockdown of MeCP2 in primary
      hippocampal neurons also resulted in reduced network integration. Interestingly,
      (1-3) IGF-1, a small peptide under clinical trial testing for RTT, rescued
      neuronal integration deficits of MeCP2-deficient neurons in vitro but not in
      vivo. In addition, (1-3) IGF treatment corrected aberrant excitability and
      network synchrony of MeCP2-deficient hippocampal neurons. Our results indicate
      that MeCP2 is essential for immature neurons to establish appropriate network
      connectivity.

PMID- 30277527
TI  - Letter to the Editor.

PMID- 30277528
TI  - Effects of Pollination by the Indo-Malaya Stingless Bee (Hymenoptera: Apidae) on
      the Quality of Greenhouse-Produced Rockmelon.
AB  - Rockmelon (Cucumis melo Linnaeus (Cucurbitales: Cucurbitaceae)) is a novel
      commercialized fruit in Malaysia and has great potential to become an important
      horticultural crop for the international market. In this study, we investigated
      the effects of pollination by the Indo-Malaya stingless bee Heterotrigona itama
      Smith (Hymenoptera: Apidae) on measures of yield and quality of rockmelon
      cultivated in the greenhouse, compared with hand cross-pollination and self
      pollination. Results showed that rockmelon produced from plants pollinated by
      stingless bees and hand cross-pollination had higher fruit set, were heavier and
      larger, and contained higher numbers of seed per fruit compared with those
      produced by self-pollination. Pollination by stingless bees produced fruit with
      greater sweetness than either hand cross-pollination or self-pollination. This
      study demonstrated that stingless bee pollination produced rockmelon fruit of
      similar quality, but better yields compared to the other pollination treatments.
      We showed that stingless bees should be considered as an alternative, effective
      pollinator for the improved production of high quality rockmelon in commercial
      greenhouse cultivation.

PMID- 30277529
TI  - Country-level welfare-state measures and change in wellbeing following work exit
      in early old age: evidence from 16 European countries.
AB  - Background: Although the effects of individual-level factors on wellbeing change
      following work exit have been identified, the role of welfare-state variables at
      the country level has yet to be investigated. Methods: Data on 8037 respondents
      aged 50 years and over in 16 European countries were drawn from the Survey of
      Health, Ageing and Retirement in Europe (SHARE) and the English Longitudinal
      Study of Ageing (ELSA). We employed multilevel models to assess determinants of
      change in wellbeing following work exit, using CASP-12 change scores. After
      adjusting for institutionally defined route and timing of work exit, in addition
      to other individual-level variables, we tested country-level variables including
      welfare-state regime and measures of disaggregated welfare spending to determine
      their associations with wellbeing change and the proportion of between-country
      variance explained. Results: Individuals whose exit from paid work was
      involuntary or diverged from the typical retirement age experienced declines in
      wellbeing. Country effects accounted for 7% of overall variance in wellbeing
      change. Individuals residing in countries with a Mediterranean welfare regime
      experienced more negative changes in wellbeing, with a difference of -2.15 (
      3.23, -1.06) CASP-12 points compared with those in Bismarckian welfare states.
      Welfare regime explained 62% of between-country variance. National per-capita
      expenditure on non-healthcare in-kind benefits (services) was associated with
      more positive wellbeing outcomes. Conclusions: National expenditure on in-kind
      benefits, particularly non-healthcare services, is associated with more
      favourable wellbeing change outcomes following work exit in early old age.
      Welfare-state effects explain the majority of between-country differences in
      change in wellbeing.

PMID- 30277530
TI  - Response to Letter to the Editor.

PMID- 30277531
TI  - Laboratory and Field Assessments of Erythritol Derivatives on the Survival,
      Reproductive Rate, and Control of Drosophila suzukii (Diptera: Drosophilidae).
AB  - Spotted-wing Drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae)
      is a vinegar fly introduced unintentionally into the United States. Since 2008,
      D. suzukii has reduced annual berry yields from 6 to 100%. Effective control of
      D. suzukii during harvest requires weekly applications of low-residual, broad
      spectrum insecticides that are unavailable for organic farming. A novel
      ingestible insecticide, a 4-carbon polyol, mesoerythritol (erythritol), was found
      to kill 75 to 100% of larval and adult D. suzukii. However, mesoerythritol, at
      effective concentrations (0.5-1.0M), may be cost-prohibitive. Therefore, we
      conducted laboratory tests to assess the effects of lower cost derivatives of
      erythritol, namely the pentaerythritol series of 1,3-diols on D. suzukii pupal
      production, adult production, adult mortality, brood output, and reproductive
      increase. We then selected the two most promising compounds for a field test on
      fruiting rabbiteye blueberry. From 90 to 100% of adults died when fed food
      moistened with 1M solutions of mesoerythritol and pentaerythritol. Mesoerythritol
      and dipentaerythritol at a concentration of 1M were ovicidal/larvicidal, killing
      >=85% of immatures. Overall, 1M mesoerythritol killed 80% or more larvae and
      adults, thus bringing populations to near zero. The heaviest compound of this
      series, tripentaerythritol, at all concentrations, was largely benign to both
      adults and immatures. Thus, we cannot recommend tripentaerythritol for D. suzukii
      control. In a blueberry field, 0.5M mesoerythritol and 0.5M pentaerythritol, each
      by themselves, reduced egg infestation by 64% and larval infestation by 93%;
      their combination (0.25M mesoerythritol and 0.25M pentaerythritol) achieved even
      greater egg control with 82% fewer eggs infesting blueberry fruits.

PMID- 30277532
TI  - Corrigendum to "Fecundity and Egg Laying in Helicoverpa armigera (Lepidoptera:
      Noctuidae): Model Development and Field Validation".

PMID- 30277533
TI  - Association between early history of asthma and COPD diagnosis in later life: a
      systematic review and meta-analysis.
AB  - Background: Whereas most studies have reported prior history/diagnosis of asthma
      as an independent risk factor for chronic obstructive pulmonary disease (COPD)
      development in later life, no systematic review and meta-analysis has been
      conducted to synthesize these observational studies. The aim of this review is to
      investigate associations between prior history of asthma and later development of
      COPD. Methods: We conducted a comprehensive search in PubMed, CINAHL and EMBASE
      for studies related to prior history of asthma and COPD diagnosis. Articles were
      screened for relevance by two independent reviewers. Methodological quality was
      independently assessed and data extracted for qualitative and quantitative
      review. We explored heterogeneity and performed a publication bias check.
      Results: From the 1260 articles retrieved, 9 were included in the qualitative
      review and 7 in the meta-analysis. History of asthma was associated with
      developing COPD in later life (Inverse Variance Random-effects model, odds ratio:
      7.87, 95% confidence interval: 5.40-11.45, p < 0.00001). Conclusions: Studies
      with high methodological quality provided sufficient evidence to suggest that
      individuals with previous history of asthma have an increasing likelihood of
      developing COPD in later life.

PMID- 30277534
TI  - Editorial: We need to talk about authorship.
AB  - In our day-to-day editorial work at GigaScience, time and again we see issues
      cropping up that make us worry whether everyone understands good scientific
      practice when it comes to listing author names on the title page. There are many
      issues that underlie inappropriate authorship designations, but there are also
      guidelines to help potential authors determine when and how a researcher should
      be included with a manuscript. Here, we help clarify this and also provide a
      clear statement of our expectations around how authors are assigned to
      manuscripts submitted to GigaScience.

PMID- 30277535
TI  - Disentangling Within- and Between-Person Effects of Shared Risk Factors on E
      cigarette and Cigarette Use Trajectories From Late Adolescence to Young
      Adulthood.
AB  - Background: Longitudinal studies report associations between use of electronic
      cigarettes (ECs) and cigarettes over time among young people, but do not
      distinguish within- from between-person effects, which complicates interpretation
      of findings. Further, the role of shared risk factors, such as substance use and
      mental health, in explaining longitudinal associations between EC and cigarette
      use remains unclear. This study used within- and between-person analyses to
      assess longitudinal associations between youths' EC and cigarette use and shared
      risk factors. Methods: Between 2015 and 2017, 2039 youths completed three Web
      based surveys, allowing us to model EC and cigarette use from ages 16 to 20. Auto
      regressive latent growth models with structured residuals (ALT-SR) examined both
      between-person and within-person associations between past-month frequency of EC
      use, cigarette use, and third variables (alcohol and marijuana use, mental health
      symptoms) over time. Results: Models revealed robust reciprocal associations
      between EC and cigarette use, such that more frequent EC use at one time
      predicted more frequent cigarette use at the subsequent time, and vice versa.
      Between-person analyses showed associations between shared risk factors and both
      EC and cigarette use. However, shared risk factors did not predict frequency of
      subsequent EC and cigarette use in within-person analyses. Conclusions: Findings
      add to a growing body of research suggesting that EC use among youth is
      prospectively associated with progression toward greater cigarette use. Shared
      risk factors may help explain differences in EC and cigarette use patterns
      between young people, but do not appear to influence longitudinal trajectories of
      EC and cigarette use within individuals. Implications: This study examined within
      and between-person associations between e-cigarette use, cigarette use, and
      shared risk factors (alcohol use, marijuana use, mental health symptoms) in a
      longitudinal cohort of youths. Within- and between-person analyses revealed
      reciprocal prospective associations between e-cigarette and cigarette use,
      suggesting a progression toward more frequent use of both products over time. The
      shared risk factors examined here did not affect escalations in e-cigarette or
      cigarette use over time within individuals, but likely influence which youths use
      these products. Findings add to a growing body of evidence suggesting that e
      cigarette use increases subsequent cigarette use in young people.

PMID- 30277536
TI  - Combined Iron Oxide Nanoparticle Ferumoxytol and Gadolinium Contrast Enhanced MRI
      Defines Glioblastoma Pseudo-progression.
AB  - Background: Noninvasively differentiating therapy-induced pseudo-progression from
      recurrent disease in patients with glioblastoma is prospectively difficult due to
      the current lack of a biologically specific imaging metric. Ferumoxytol iron
      oxide nanoparticle MRI contrast characterizes innate immunity mediated
      neuroinflammation; therefore, we hypothesized that combined ferumoxytol and
      gadolinium enhanced MRI could serve as a biomarker of glioblastoma pseudo
      progression. Methods: In this institutional review board approved, retrospective
      study, we analyzed ferumoxytol and gadolinium contrast enhanced T1-weighted 3T
      MRI in 45 patients with glioblastoma over multiple clinical time points. IDH-1
      mutational status was characterized by exome sequencing. Sum of products diameter
      measurements were calculated according to RANO criteria from both gadolinium and
      ferumoxytol enhanced sequences. Enhancement mismatch was calculated as the
      natural log of the ferumoxytol to gadolinium sum of products diameter ratio.
      Analysis of variance and Students t-test assessed differences in mismatch ratios.
      P-value < 0.05 indicated statistical significance. Results: With the development
      of pseudo-progression we observed a significantly elevated mismatch ratio when
      compared to disease recurrence (P< 0.01) within IDH-1 wild type patients.
      Patients with IDH-1 mutation demonstrated significantly reduced mismatch ratio
      with the development of pseudo-progression when compared to disease recurrence
      (P< 0.01). Receiver operator curve analysis demonstrated 100% sensitivity and
      specificity for the use of mismatch ratios as a diagnostic biomarker of pseudo
      progression. Conclusion: Our study suggests that ferumoxytol to gadolinium
      contrast mismatch ratios are a MRI biomarker for the diagnosis of pseudo
      progression in patients with glioblastoma. This may be due to the unique
      characterization of therapy-induced neuroinflammation.

PMID- 30277538
TI  - N2M2 (NOA20) phase I/II trial of molecularly matched targeted therapies plus
      radiotherapy in patients with newly diagnosed non-MGMT hypermethylated
      glioblastoma.
AB  - Background: Patients with glioblastoma without O6-methyl guanine O6
      methylatransferase (MGMT) promoter hypermethylation are unlikely to benefit from
      alkylating chemotherapy with temozolomide (TMZ). Trials aiming at replacing TMZ
      with targeted agents in unselected patient populations have failed to demonstrate
      any improvement of survival. Advances in molecular understanding and diagnostic
      precision enable identification of key genetic alterations in a timely manner and
      in principle allow treatments with targeted compounds based on molecular markers.
      Methods and analysis: The NCT Neuro Master Match (N2M2) trial is an open label
      multicenter phase I/IIa umbrella trial for patients with newly diagnosed
      isocitrate dehydrogenase (IDH) wildtype glioblastoma without MGMT promoter
      hypermethylation to show safety, feasibility and preliminary efficacy of
      treatment with targeted compounds in addition to standard radiotherapy based on
      molecular characterization. N2M2 is formally divided in a DISCOVERY and a
      TREATMENT part. DISCOVERY includes broad molecular neuropathological diagnostics
      to detect predefined biomarkers for targeted treatments. Molecular diagnostics
      and bioinformatic evaluation are performed within four weeks, allowing a timely
      initiation of postoperative treatment. Stratification for TREATMENT takes place
      in five subtrials, including alectinib, idasanutlin, palbociclib, vismodegib and
      temsirolimus as targeted therapies, according to the best matching molecular
      alteration. Patients without matching alterations are randomized between
      subtrials without strong biomarkers using atezolizumab and asinercept (APG101),
      and the standard of care, TMZ. For the phase I parts, a Bayesian criterion is
      used for continuous monitoring of toxicity. In the phase II trials, progression
      free survival at six months is used as endpoint for efficacy.

PMID- 30277540
TI  - Nursing Education: Our Iceberg Is Melting.

PMID- 30277537
TI  - The bacterial Mre11-Rad50 homolog SbcCD cleaves opposing strands of DNA by two
      chemically distinct nuclease reactions.
AB  - The Mre11-Rad50 complex is a DNA double-strand break sensor that cleaves blocked
      DNA ends and hairpins by an ATP-dependent endo/exonuclease activity for
      subsequent repair. For that, Mre11-Rad50 complexes, including the Escherichia
      coli homolog SbcCD, can endonucleolytically cleave one or both strands near a
      protein block and process free DNA ends via a 3'-5' exonuclease, but a unified
      basis for these distinct activities is lacking. Here we analyzed DNA binding,
      ATPase and nuclease reactions on different DNA substrates. SbcCD clips terminal
      bases of both strands of the DNA end in the presence of ATPgammaS. It introduces
      a DNA double-strand break around 20-25 bp from a blocked end after multiple
      rounds of ATP hydrolysis in a reaction that correlates with local DNA
      meltability. Interestingly, we find that nuclease reactions on opposing strands
      are chemically distinct, leaving a 5' phosphate on one strand, but a 3' phosphate
      on the other strand. Collectively, our results identify an unexpected chemical
      variability of the nuclease, indicating that the complex is oriented at a free
      DNA end and facing a block with opposite polarity. This suggests a unified model
      for ATP-dependent endo- and exonuclease reactions at internal DNA near a block
      and at free DNA ends.

PMID- 30277541
TI  - Relationship of Multiple Attempts on an Admissions Examination to Early Program
      Performance.
AB  - BACKGROUND: When a student makes multiple attempts at an admissions assessment,
      an institution must decide how to incorporate the resulting information into its
      admissions decision. However, little research exists to guide this decision
      within a nursing admissions context. METHOD: This article examines patterns in
      retesting scores from a nursing admissions assessment and the correlations of
      four retesting score treatments with scores on an early program assessment.
      RESULTS: Although test scores do increase with each subsequent attempt, the
      average of all attempt scores is more highly correlated, in almost all instances,
      with future performance in a nursing program than any one test score. CONCLUSION:
      These results indicate that nursing programs presented with multiple scores from
      an examinee would be best served by using an average of all available scores when
      making admissions decisions. [J Nurs Educ. 2018;57(10):578-583.].

PMID- 30277542
TI  - Nursing Faculty Perceptions of Service-Learning: An Integrative Review.
AB  - BACKGROUND: Nursing faculty plays a central role in facilitating service learning
      experiences, yet little is known about their perceptions of service-learning.
      METHOD: Whit-temore's and Knafl's method for integrative review was used to
      analyze sources from CINAHL, ERIC, MEDLINE Complete, ProQuest LLC, and
      ScienceDirect. RESULTS: Literature about nursing faculty perceptions of service
      learning was scarce. Therefore, a thematic analysis was completed on 17 diverse
      sources regarding general faculty perceptions. CONCLUSION: Limited research was
      discovered related to nursing faculty perceptions, exposing a gap in the
      literature. Further research may clarify the role of service-learning in nursing
      education. [J Nurs Educ. 2018;57(10):584-589.].

PMID- 30277543
TI  - Registered Nurses' Experiences of Passing the NCLEX-RN After More Than One
      Attempt.
AB  - BACKGROUND: In the past decade, little research has been conducted regarding
      individuals' stories about not initially being successful on the National Council
      Licensure Examination for Registered Nurses. An unsuccessful licensure
      examination attempt may affect the individual personally and profoundly in ways
      that could influence their future success. METHOD: Individual in-depth interviews
      were conducted once with 15 RNs who were initially unsuccessful on the licensure
      examination and subsequently passed. Data analyses were conducted using both
      manual and electronic coding through thematic identification. Rigor was ensured
      by meeting quality criteria for qualitative research. RESULTS: Four themes were
      identified: (a) Pressures all Around, (b) the Stigma of Being Unsuccessful, (c)
      Correcting the Problems, and (d) Ultimate Triumph in Discovery. CONCLUSION:
      Following their initial unsuccessful National Council Licen-sure Examination for
      Registered Nurses results, participants were deeply affected, but after accepting
      help from family, friends, nursing instructors, and managers, they were able to
      move forward, change their approaches, and become RNs. [J Nurs Educ.
      2018;57(10):590-597.].

PMID- 30277544
TI  - Clinical Research Nursing: Awareness and Understanding Among Baccalaureate
      Nursing Students.
AB  - BACKGROUND: The American Nurses Association recognizes the specialty practice of
      Clinical Research Nursing, but many new nurses are unaware of the specialty and
      lack knowledge to effectively interact with research teams. METHOD: Participants
      completed a novel online survey to describe the level of awareness and
      understanding of the clinical research nursing specialty and the effect of
      clinical studies on nursing practice in fourth-year baccalaureate nursing program
      students. RESULTS: Ninety-three participants completed the survey. Most were
      aware that some nurses specialize in the care of clinical study participants, and
      most did not know how to effectively support research teams. Years of nursing
      experience was associated with an understanding of how to effectively collaborate
      with clinical research nurses and an interest in a career as a clinical research
      nurse. CONCLUSION: Entry-level nursing programs should expose students to the
      clinical research nurse role and provide the knowledge needed to collaborate with
      researchers when caring for patients in clinical studies. [J Nurs Educ.
      2018;57(10):598-603.].

PMID- 30277545
TI  - Increasing Psychiatric Mental Health Nursing HESI Grade Allocation Percentage in
      a Psychiatric Nursing Course.
AB  - BACKGROUND: Scant evidence is found in the literature regarding the unit-level
      Health Education Systems, Inc. (HESI) examinations. This study aims to (a)
      compare student Psych HESI examination scores between cohorts after increasing
      grade allocation from 5% to 15%, and (b) examine student perceptions of the
      impact of increasing the percentage of course grade allocation. METHOD: An ex
      post facto research design analyzed differences in Psych HESI examination scores.
      HESI examination mean score differences between groups were analyzed using ANOVA.
      Narrative responses were analyzed using content analysis. RESULTS: Psych HESI
      examination means increased from 836 in spring 2015 (5% of course grade) to 905
      in fall 2015 (15% of course grade). Narrative response themes included (a)
      Validated Learning; (b) Compelled Participants to Study More; (c) Incongruent
      With Class Content and Preparation Books; and (d) Stress-Producing. CONCLUSION:
      HESI examination scores improved with increasing course grade percentage
      allocated to the HESI score. Students indicated positive and negative perceptions
      of the increased grade allocation. [J Nurs Educ. 2018;57(10):604-608.].

PMID- 30277546
TI  - Comparison of Two Methods of Teaching Culture to Bachelor of Science in Nursing
      Students.
AB  - BACKGROUND: The nursing literature examining effective methods to teach
      transcultural self-efficacy demonstrates inconsistent findings. This study
      evaluated the effectiveness of a nursing stand-alone culture course with
      concurrent field experiences compared with the standard integrated culture
      content in the curriculum in increasing transcultural self-efficacy in nursing
      students. METHOD: This quasi-experimental, static-group comparison used the
      Transcultural Self-Efficacy Tool to measure outcomes. The treatment group
      consisted of first-semester nursing students (n = 53) enrolled in a pilot 2
      credit culture course. The control group consisted of graduating senior nursing
      students (n = 19) who had culture integrated throughout the curriculum. RESULTS:
      The posttest of the first-semester students in the treatment group scored higher
      than either their pretest or the graduating senior students (control group).
      CONCLUSION: The stand-alone culture course had a greater positive effect than the
      integrated culture content on students' transcultural self-efficacy. [J Nurs
      Educ. 2018;57(10):609-613.].

PMID- 30277547
TI  - Stereotype Threat in Male Nurse-Patient Interactions.
AB  - BACKGROUND: Stereotype threat describes the apprehension individuals experience
      from the prospect of confirming negative self-relevant stereotypes. Due to their
      minority status, male nurses are believed to be susceptible to stereotype threat
      effects in the field of nursing. METHOD: One hundred eighty-three male nursing
      students were randomly assigned to one of three evaluative frames (patient
      management, empathy, or control) and tasked with completing an online patient
      simulation experiment. With empathy serving as a form of stereotype threat,
      participant responses were analyzed for tentative language use. RESULTS: An
      interaction effect (patient gender * frame) was observed, where participants were
      most tentative when the simulation involved a male patient in the empathy frame.
      CONCLUSION: Findings from the study offer encouragement as the communicative
      abilities of participants were not consistently influenced under conditions of
      stereotype threat. This provides support for the need to forearm male nurses
      against the pernicious effects of gender-based stereotypes. [J Nurs Educ.
      2018;57(10):614-619.].

PMID- 30277548
TI  - Academic-Practice Partnership: Benefits and Sustainability of the Northeast
      Region VA Nursing Alliance.
AB  - BACKGROUND: The Northeast Region VA Nursing Alliance is an academic-practice
      partnership founded in 2007 between the Veteran's Administration (VA)
      Boston/Bedford HealthCare Systems and six schools of nursing. METHOD: The purpose
      of this retrospective review was to examine the outcomes of the Northeast Region
      VA Nursing Alliance in accordance with the mission, goals, and sustainability of
      the alliance. RESULTS: The review confirmed that the alliance has successfully
      accomplished the mission and goals and continues to be a leader in academic
      practice partnerships. CONCLUSION: Since inception, the academic-practice
      partnership has increased the number of clinical rotations and clinical faculty,
      educated nursing students on the care of Veterans, developed dedicated
      educational nursing units, increased Veteran-centered research, and provided a
      plethora of educational programs to increase knowledge related to Veteran health
      care issues. [J Nurs Educ. 2018;57(10):620-623.].

PMID- 30277539
TI  - Associations of obesity and circulating insulin and glucose with breast cancer
      risk: a Mendelian randomization analysis.
AB  - Background: In addition to the established association between general obesity
      and breast cancer risk, central obesity and circulating fasting insulin and
      glucose have been linked to the development of this common malignancy. Findings
      from previous studies, however, have been inconsistent, and the nature of the
      associations is unclear. Methods: We conducted Mendelian randomization analyses
      to evaluate the association of breast cancer risk, using genetic instruments,
      with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI
      adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of
      these instruments with type 2 diabetes risk in a large diabetes genome-wide
      association study consortium. We then investigated their associations with breast
      cancer risk using individual-level data obtained from 98 842 cases and 83 464
      controls of European descent in the Breast Cancer Association Consortium.
      Results: All sets of instruments were associated with risk of type 2 diabetes.
      Associations with breast cancer risk were found for genetically predicted fasting
      insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95%
      confidence interval (CI) = 1.26-2.31, p  =  5.09  *  10-4], 2-h glucose (OR =
      1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  *  10-4), BMI (OR = 0.70
      per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  *  10-19) and WHRadj BMI (OR
      = 0.85, 95% CI = 0.79-0.91, p  =  9.22  *  10-6). Stratified analyses showed that
      genetically predicted fasting insulin was more closely related to risk of
      estrogen-receptor [ER]-positive cancer, whereas the associations with instruments
      of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal
      status, estrogen receptor status and family history of breast cancer.
      Conclusions: We confirmed the previously reported inverse association of
      genetically predicted BMI with breast cancer risk, and showed a positive
      association of genetically predicted fasting insulin and 2-h glucose and an
      inverse association of WHRadj BMI with breast cancer risk. Our study suggests
      that genetically determined obesity and glucose/insulin-related traits have an
      important role in the aetiology of breast cancer.

PMID- 30277550
TI  - An Innovative Physical Assessment Simulation for Accelerated Master's in Nursing
      Students.

PMID- 30277549
TI  - Using Simulation to Teach Telehealth Nursing Competencies.
AB  - BACKGROUND: The use of telehealth to provide care to millions of patients who
      have difficulty accessing care through traditional means is growing
      exponentially. Nurse educators must prepare students to meet the challenge of
      managing this mode of care delivery. METHOD: A simulated telehealth experience
      was designed using the International Nursing Association for Clinical Simulation
      and Learning Standards of Best Practice: SimulationTM, student learning
      objectives, and telehealth competencies. The design promoted active participation
      in a telehealth visit with a standardized patient. RESULTS: The simulation
      provided students with the opportunity to demonstrate use of telehealth equipment
      and become familiar with telehealth competencies. This hands-on experience
      increased student engagement related to telehealth as a health care delivery
      option and was an effective objective structured clinical examination.
      CONCLUSION: Integration of telehealth into the nursing curriculum is a necessity
      as health care technology advances. Simulation is one strategy available to
      expose students to telehealth and increase student engagement. [J Nurs Educ.
      2018;57(10):624-627.].

PMID- 30277551
TI  - Use of Parallel Charting With Senior-Level Baccalaureate Nursing Students.

PMID- 30277552
TI  - An Innovative Strategy for Community Nursing Student Simulation Experiences.

PMID- 30277553
TI  - Welcome to the Clinical Nurse Leader Shark Tank.

PMID- 30277554
TI  - [Emergency management of chemical eye burns].
AB  - Chemical burn injury of the eye is a medical emergency that requires immediate
      intervention and structured ophthalmic assessment without unnecessary delay.
      Chemicals, alkali in particular but also acids, cause profound damage to the
      anatomy of the ocular surface or even deeper eye structures. The injury is
      potentially sight-threatening and can, in the worst cases, lead to loss of the
      eye. Reconstructive surgery is complex and often involves multiple surgeries but
      can give very good results in carefully selected cases. This article summarizes
      present evidence-based guidelines relevant for Swedish conditions and in use at
      St. Erik Eye Hospital in Stockholm.

PMID- 30277555
TI  - ?

PMID- 30277556
TI  - Antihypertensive drug therapy for mild to moderate hypertension during pregnancy.
AB  - BACKGROUND: Antihypertensive drugs are often used in the belief that lowering
      blood pressure will prevent progression to more severe disease, and thereby
      improve pregnancy outcome. This Cochrane Review is an updated review, first
      published in 2001 and subsequently updated in 2007 and 2014. OBJECTIVES: To
      assess the effects of antihypertensive drug treatments for women with mild to
      moderate hypertension during pregnancy. SEARCH METHODS: We searched Cochrane
      Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO
      International Clinical Trials Registry Platform (ICTRP) (13 September 2017), and
      reference lists of retrieved studies. SELECTION CRITERIA: All randomised trials
      evaluating any antihypertensive drug treatment for mild to moderate hypertension
      during pregnancy, defined as systolic blood pressure 140 to 169 mmHg and/or
      diastolic blood pressure 90 to 109 mmHg. Comparisons were of one or more
      antihypertensive drug(s) with placebo, with no antihypertensive drug, or with
      another antihypertensive drug, and where treatment was planned to continue for at
      least seven days. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed trials for inclusion and risk of bias, extracted data and checked them
      for accuracy. MAIN RESULTS: For this update, we included 63 trials (data from 58
      trials, 5909 women), with moderate to high risk of bias overall.We carried out
      GRADE assessments for the main 'antihypertensive drug versus placebo/no
      antihypertensive drug' comparison only. Evidence was graded from very low to
      moderate certainty, with downgrading mainly due to design limitations and
      imprecision.For many outcomes, trials contributing data evaluated different
      hypertensive drugs; while we did not downgrade for this indirectness, results
      should be interpreted with caution.Antihypertensive drug versus placebo/no
      antihypertensive drug (31 trials, 3485 women)Primary outcomes: moderate-certainty
      evidence suggests that use of antihypertensive drug(s) probably halves the risk
      of developing severe hypertension (risk ratio (RR) 0.49; 95% confidence interval
      (CI) 0.40 to 0.60; 20 trials, 2558 women), but may have little or no effect on
      the risk of proteinuria/pre-eclampsia (average risk ratio (aRR) 0.92; 95% CI 0.75
      to 1.14; 23 trials, 2851 women; low-certainty evidence). Moderate-certainty
      evidence also shows that antihypertensive drug(s) probably have little or no
      effect in the risk of total reported fetal or neonatal death (including
      miscarriage) (aRR 0.72; 95% CI 0.50 to 1.04; 29 trials, 3365 women), small-for
      gestational-age babies (aRR 0.96; 95% CI 0.78 to 1.18; 21 trials, 2686 babies) or
      preterm birth less than 37 weeks (aRR 0.96; 95% CI 0.83 to 1.12; 15 trials, 2141
      women). SECONDARY OUTCOMES: we are uncertain of the effect of antihypertensive
      drug(s) on the risk of maternal death, severe pre-eclampsia, or eclampsia,
      orimpaired long-term growth and development of the baby in infancy and childhood,
      because the certainty of this evidence is very low. There may be little or no
      effect on the risk of changed/stopped drugs due to maternal side-effects, or
      admission to neonatal or intensive care nursery (low-certainty evidence). There
      is probably little or no difference in the risk of elective delivery (moderate
      certainty evidence).Antihypertensive drug versus another antihypertensive drug
      (29 trials, 2774 women)Primary outcomes: beta blockers and calcium channel
      blockers together in the meta-analysis appear to be more effective than
      methyldopa in avoiding an episode of severe hypertension (RR 0.70; 95% CI 0.56 to
      0.88; 11 trials, 638 women). There was also an increase in this risk when other
      antihypertensive drugs were compared with calcium channel blockers (RR 1.86; 95%
      CI 1.09 to 3.15; 5 trials, 223 women), but no evidence of a difference when
      methyldopa and calcium channel blockers together were compared with beta blockers
      (RR1.18, 95% CI 0.95 to 1.48; 10 trials, 692 women). No evidence of a difference
      in the risk of proteinuria/pre-eclampsia was found when alternative drugs were
      compared with methyldopa (aRR 0.78; 95% CI 0.58 to 1.06; 11 trials, 997 women),
      with calcium channel blockers (aRR: 1.24, 95% CI 0.70 to 2.19; 5 trials, 375
      women), or with beta blockers (aRR 1.21, 95% CI 0.88 to 1.67; 12 trials, 1107
      women).For the babies, we found no evidence of a difference in the risk oftotal
      reported fetal or neonatal death (including miscarriage) when comparing other
      antihypertensive drugs with methyldopa (aRR 0.77, 95% CI 0.52 to 1.14; 22 trials,
      1791 babies), with calcium channel blockers (aRR 0.90, 95% CI 0.52 to 1.57; nine
      trials, 700 babies), or with beta blockers (aRR: 1.23, 95% CI 0.81 to 1.88; 19
      trials, 1652 babies); nor in the risk for small-for-gestational age in the
      comparison with methyldopa (aRR 0.79, 95% CI 0.52 to 1.20; seven trials, 597
      babies), with calcium channel blockers (aRR 1.05, 95% CI 0.64 to 1.73; four
      trials, 200 babies), or with beta blockers (average RR 1.13, 95% CI 0.80 to 1.60;
      7 trials, 680 babies). No evidence of an overall difference among groups in the
      risk of preterm birth (less than 37 weeks) was found in the comparison with
      methyldopa (aRR: 0.91; 95% CI 0.68 to 1.22; 11 trials, 835 women), with calcium
      channel blockers (aRR 0.85, 95% CI 0.59 to 1.23; six trials, 330 women), or with
      beta blockers (aRR 1.22, 95% CI 0.90 to 1.66; 9 trials, 806 women). SECONDARY
      OUTCOMES: There were no cases of maternal death andeclampsia. There is no
      evidence of a difference in the risk of severe pre-eclampsia, changed/stopped
      drug due to maternal side-effects, elective delivery, admission to neonatal or
      intensive care nursery when other antihypertensive drugs are compared with
      methyldopa, calcium channel blockers or beta blockers. Impaired long-term growth
      and development in infancy and childhood was not reported for these comparisons.
      AUTHORS' CONCLUSIONS: Antihypertensive drug therapy for mild to moderate
      hypertension during pregnancy reduces the risk of severe hypertension. The effect
      on other clinically important outcomes remains unclear. If antihypertensive drugs
      are used, beta blockers and calcium channel blockers appear to be more effective
      than the alternatives for preventing severe hypertension. High-quality large
      sample-sized randomised controlled trials are required in order to provide
      reliable estimates of the benefits and adverse effects of antihypertensive
      treatment for mild to moderate hypertension for both mother and baby, as well as
      costs to the health services, women and their families.

PMID- 30277557
TI  - Preclinical three-dimensional colorectal cancer model: The next generation of in
      vitro drug efficacy evaluation.
AB  - Colorectal cancer (CRC), the third most common cancer diagnosed in both men and
      women in the United States, shows a highly ineffective therapeutic management. In
      these years neither substantial improvements nor new therapeutic approaches have
      been provided to patients. Performing the early lead discovery phases of new
      cancer drugs in cellular models, resembling as far as possible the real in vivo
      tumor environment, may be more effective in predicting their future success in
      the later clinical phases. In this review, we critically describe the most
      representative bioengineered models for anticancer drug screening in CRC from the
      conventional two-dimensional models to the new-generation three-dimensional
      scaffold-based ones. The scaffold aims to replace the extracellular matrix, thus
      influencing the biomechanical, biochemical, and biological properties of cells
      and tissues. In this scenario, we believe that reconstitution of tumor condition
      is mandatory for an alternative in vitro methods to study cancer development and
      therapeutic strategies.

PMID- 30277558
TI  - Variation in the vital rates of an Antarctic marine predator: the role of
      individual heterogeneity.
AB  - Variation in life-history traits such as lifespan and lifetime reproductive
      output is thought to arise, in part, due to among-individual differences in the
      underlying probabilities of survival and reproduction. However, the stochastic
      nature of demographic processes can also generate considerable variation in
      fitness-related traits among otherwise-identical individuals. An improved
      understanding of life-history evolution and population dynamics therefore depends
      on evaluating the relative role of each of these processes. Here, we used a 33-yr
      data set with reproductive histories for 1,274 female Weddell seals from Erebus
      Bay, Antarctica, to assess the strength of evidence for among-individual
      heterogeneity in the probabilities of survival and reproduction, while accounting
      for multiple other sources of variation in vital rates. Our analysis used recent
      advances in Bayesian model selection techniques and diagnostics to directly
      compare model fit and predictive power between models that included individual
      effects on survival and reproduction to those that did not. We found strong
      evidence for costs of reproduction to both survival and future reproduction, with
      breeders having rates of survival and subsequent reproduction that were 3% and 6%
      lower than rates for non-breeders. We detected age-related changes in the rates
      of survival and reproduction, but the patterns differed for the two rates.
      Survival rates steadily declined from 0.92 at age 7 to 0.56 at the maximal age of
      31 yr. In contrast, reproductive rates increased from 0.68 at age 7 to 0.79 at
      age 16 and then steadily declined to 0.37 for the oldest females. Models that
      included individual effects explained more variation in observed life histories
      and had better estimated predictive power than those that did not, indicating
      their importance in understanding sources of variation among individuals in life
      history traits. We found that among-individual heterogeneity in survival was
      small relative to that for reproduction. Our study, which found patterns of
      variation in vital rates that are consistent with a series of predictions from
      life-history theory, is the first to provide a thorough assessment of variation
      in important vital rates for a long-lived, high-latitude marine mammal while
      taking full advantage of recent developments in model evaluation.

PMID- 30277559
TI  - Pharmacogenomics of Vincristine-Induced Peripheral Neuropathy: Progress
      Continues.
AB  - Vincristine is a widely used anticancer drug for the treatment of leukemia,
      lymphoma, and many solid tumors in children and adults. A major adverse effect of
      vincristine is peripheral neuropathy, which can be either sensory or motor in
      nature. The current issue of CPT reports new research that extends prior work
      identifying an inherited germline polymorphism that predisposes to vincristine
      induced neuropathy.

PMID- 30277560
TI  - Sample Selection for Medicare Risk Adjustment Due to Systematically Missing Data.
AB  - OBJECTIVE: To assess the issue of nonrepresentative sampling in Medicare
      Advantage (MA) risk adjustment. DATA SOURCES: Medicare enrollment and claims data
      from 2008 to 2011. DATA EXTRACTION: Risk adjustment predictor variables were
      created from 2008 to 2010 Part A and B claims and the Medicare Beneficiary
      Summary File. Spending is based on 2009-2011 Part A and B, Durable Medical
      Equipment, and Home Health Agency claims files. STUDY DESIGN: A propensity-score
      matched sample of Traditional Medicare (TM) beneficiaries who resembled MA
      enrollees was created. Risk adjustment formulas were estimated using multiple
      techniques, and performance was evaluated based on R2 , predictive ratios, and
      formula coefficients in the matched sample and a random sample of TM
      beneficiaries. PRINCIPAL FINDINGS: Matching improved balance on observables, but
      performance metrics were similar when comparing risk adjustment formula results
      fit on and evaluated in the matched sample versus fit on the random sample and
      evaluated in the matched sample. CONCLUSIONS: Fitting MA risk adjustment formulas
      on a random sample versus a matched sample yields little difference in MA plan
      payments. This does not rule out potential improvements via the matching method
      should reliable MA encounter data and additional variables become available for
      risk adjustment.

PMID- 30277561
TI  - The imbalance of Th17/Treg axis involved in the pathogenesis of preeclampsia.
AB  - PROBLEM: Inappropriate activation of the immune system, particularly the
      imbalance of T-helper type 17 (Th17)/regulatory T (Treg) cells is thought to play
      considerable roles in preeclampsia (PE). To investigate the probable effects of
      the adaptive immune system in the pathophysiology of PE, we analyzed the dynamic
      changes of Th17/Treg cells, cytokines profile, and transcription pattern of
      Th17/Treg-related genes and microRNAs (miRNAs) in 50 women suffering from PE in
      comparison with 50 healthy pregnant women. METHODS: Expressions of cytokines,
      specific transcription factors, and related miRNAs were measured by real-time
      polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) was
      used to test the interleukin (IL)-17, IL-23, IL-6, and IL-10 and transforming
      growth factor beta in serum and supernatant of peripheral blood mononuclear cells
      (PBMCs). The frequency of Th17 and Treg cells were determined by flow cytometry.
      RESULTS: PE patients exhibited a decreased number of Treg cells (p = 0.006),
      while Th17 cells were increased ( p = 0.004). Forkhead box P3 and IL-10 mRNA
      expressions were reduced ( p = 0.0001 and 0.0028, respectively), while
      expressions of retinoic acid receptor-related orphan nuclear receptor gammat, IL
      17, IL-23, and IL-6 were enhanced ( p < 0.0001, 0.0018, 0.0014, and 0.027,
      respectively). ELISA results also showed increased levels of IL-6, IL-17, and IL
      23 ( p = 0.022, 0.0005, 0.0081, respectively), and decreased levels of IL-10 in
      the supernatant of PBMCs of PE patients compared with control group ( p =
      0.0011). There was significant upregulation of miR-106b and miR-326 ( p = 0.0048
      and 0.028, respectively) in PE patients in comparison with the control group.
      CONCLUSIONS: These findings suggest that imbalance of Th17/Treg cells, regulated
      possibly via microRNAs, may be involved in the pathogenesis of PE, emphasizing on
      the importance of these cells in feto-maternal immune cross-talk.

PMID- 30277562
TI  - The role of the dorsal striatum in choice impulsivity.
AB  - It has long been recognized that the dorsal striatum is an essential brain region
      for control of action selection based on action-outcome contingency learning,
      particularly when the available actions are bound to rewarding outcomes. In
      principle, intertemporal choice in the delay-discounting task-a validated measure
      of choice impulsivity-involves reward-associated actions that require the
      recruitment of the dorsal striatum. Here, we conjecture about ways the dorsal
      striatum is involved in choice impulsivity. Based on a selective body of studies,
      we begin with a brief history of research on choice impulsivity and the dorsal
      striatum, and then provide a comprehensive summary of contemporary studies
      utilizing human neuroimaging and animal models to search for links between choice
      impulsivity and the dorsal striatum. In particular, we discuss in-depth the
      converging evidence for the associations of choice impulsivity with the reward
      valuation coded by the caudate, a ventral-to-dorsal gradient in the dorsal
      striatum, the origins of striatal afferents, and developmental maturation of
      frontostriatal connectivity during adolescence.

PMID- 30277563
TI  - The impact of Cymbopogon martinii essential oil on Cutibacterium (formerly
      Propionibacterium) acnes strains and its interaction with keratinocytes.
AB  - OBJECTIVES: The human skin microbiota is mainly composed of bacteria belonging to
      the genera Staphylococcus, Cutibacterium, Micrococcus and Corynebacterium, but on
      the skin of the face and back, ca. 50% of the total microbiota is represented by
      the bacterium Cutibacterium acnes. The aim of this research was to evaluate the
      impact of C. martini EO and its major compound, geraniol, on C. acnes. METHODS:
      The minimum inhibitory concentration against C. acnes strains, phenotypic changes
      and responses of the proteome was determined. In addition, was assessed the
      effect of compounds in RNA-binding assay, on C. acnes-exposed keratinocytes and
      on the C. acnes type distribution on shoulder skin. KEY FINDINGS: The range of
      the MIC was 0.7 to 1.6 mg/ml for the three main C. acnes types. There were no
      cytotoxic effects of compounds in the absence or presence of C. acnes; after 7
      days of exposure to C. martini EO, we could not detect a major shift of the C.
      acnes types on shoulder skin that was found to be dominated by C. acnes strains
      of types II and IA2. CONCLUSIONS: Our work gives novel insight into the skin
      microbiota-interacting properties of C. martini EO.

PMID- 30277564
TI  - Paeonia lactiflora Pall. regulates the NF-kappaB-NLRP3 inflammasome pathway to
      alleviate cholestasis in rats.
AB  - OBJECTIVES: Cholestasis is a critical risk factor for severe hepatic disease or
      cirrhosis. The anti-inflammatory effect of Paeonia lactiflora Pall. (PLP), named
      Chishao in traditional Chinese medicine (TCM), on alpha-naphthylisothiocyanate
      (ANIT)-induced cholestasis model was tried to be elucidated in this research.
      METHODS: Therapeutic effect indices on hepatic function, including ALT, AST,
      TBIL, DBIL, ALP, TBA and gamma-GT, were measured. To further investigate the
      protective mechanism of PLP, the mRNA and protein expression levels of NF-kappaB
      NLRP3 inflammasome pathway were detected. RESULTS: Our results showed that
      compared with the model group, PLP could significantly reduce the increased serum
      indices such as ALT, AST, TBIL, DBIL, ALP, TBA and gamma-GT induced by ANIT in a
      dose-dependent way. Moreover, we found that PLP downregulated the mRNA expression
      levels including IKK, p65, NLRP3, caspase-1 and IL-1beta, especially at the large
      dose. Furthermore, PLP also significantly inhibited NF-kappaB-NLRP3 inflammasome
      pathway by decreasing the protein levels of p65, p-p65, p-IKK, NLRP3, caspase-1
      and IL-1beta. CONCLUSIONS: The results indicated that PLP could ameliorate ANIT
      induced cholestasis in rats and the anti-inflammatory effect of PLP might be
      related to regulating NF-kappaB-NLRP3 inflammasome pathway. This study will
      provide scientific evidence for PLP as a potential drug candidate for
      cholestasis.

PMID- 30277565
TI  - Sexual orientation-related oral health disparities in the United States.
AB  - OBJECTIVE: Recent reports have documented health disparities according to sexual
      orientation and used the minority stress model as a framework for understanding
      their origins. To date, however, sexual orientation-related disparities in the
      oral health domain have not been evaluated. Accordingly, this study sought to
      investigate potential health disparities in objectively-assessed and subjective
      reports of oral heath among lesbian, gay, and bisexual adults relative to the
      heterosexual community-dwelling US population. METHODS: We used three consecutive
      cycles (2009-2014) of National Health and Nutrition Examination Survey (NHANES)
      data for men and women aged 18-59 years. We examined clinical measures of dental
      caries, tooth loss, chronic periodontitis, and oral human papillomavirus (HPV) as
      well as subjective reports of oral health status and use of dental services.
      RESULTS: Clinical measures of oral disease did not differ according to sexual
      orientation; however, bisexual adults were more likely to rate their oral health
      unfavorably (41%) than heterosexual adults (27%). Gay men reported "bone loss
      around teeth" more frequently (35%) than heterosexual (11%) and bisexual (10%)
      men. Bisexual individuals were more likely to confront barriers to accessing
      dental care (30%) versus heterosexual adults (19%). CONCLUSIONS: While clinical
      measures of oral health did not substantially differ between sexual orientation
      strata, subjective measures of oral health were worse among gay, lesbian, and
      bisexual adults versus heterosexual adults. Further study of the psychosocial
      construction of oral health among sexual minorities is warranted.

PMID- 30277566
TI  - Advance Care Planning in Cognitively Impaired Older Adults.
AB  - Older adults with cognitive impairment face many healthcare challenges, chief
      among them participating in medical decision-making about their own health care.
      Advance care planning (ACP) is the process whereby individuals communicate their
      wishes for future care with their clinicians and surrogate decision-makers while
      they are still able to do so. ACP has been shown to improve important outcomes
      for individuals with cognitive impairment, but rates of ACP for these individuals
      are low because of individual-, clinician-, and system-related factors.
      Addressing ACP early in the illness trajectory can maximize the chances that
      people can participate meaningfully. This article recommends best practices for
      approaching ACP for older adults with cognitive impairment. The importance of
      providing anticipatory guidance and eliciting values to guide future care to
      create a shared framework between clinicians, individuals, and surrogate decision
      makers is emphasized. It is recommended that ACP be approached as an iterative
      process to continue to honor and support people's wishes as cognitive impairment
      progresses and increasingly threatens independence and function. The article
      describes effective strategies for assessing decision-making capacity,
      identifying surrogate decision-makers, and using structured communication tools
      for ACP. It also provides guidelines for documentation and billing. Finally,
      special considerations for individuals with advanced dementia are described,
      including the use of artificial hydration and nutrition, decisions about site of
      care, and the role of hospice care.

PMID- 30277567
TI  - Statins for Primary Prevention in Older Adults-Moving Toward Evidence-Based
      Decision-Making.
AB  - OBJECTIVES: To determine the efficacy and safety of statins for primary
      prevention of atherosclerotic cardiovascular disease (ASCVD) events in older
      adults, especially those aged 80 and older and with multimorbidity. METHODS: The
      National Institute on Aging and the National Heart, Lung and Blood Institute
      convened A multidisciplinary expert panel from July 31 to August 1, 2017, to
      review existing evidence, identify knowledge gaps, and consider whether statin
      safety and efficacy data in persons aged 75 and older without ASCVD are
      sufficient; whether existing data can inform the feasibility, design, and
      implementation of future statin trials in older adults; and clinical trial
      options and designs to address knowledge gaps. This article summarizes the
      presentations and discussions at that workshop. RESULTS: There is insufficient
      evidence regarding the benefits and harms of statins in older adults, especially
      those with concomitant frailty, polypharmacy, comorbidities, and cognitive
      impairment; a lack of tools to assess ASCVD risk in those aged 80 and older; and
      a paucity of evidence of the effect of statins on outcomes of importance to older
      adults, such as statin-associated muscle symptoms, cognitive function, and
      incident diabetes mellitus. Prospective, traditional, placebo-controlled,
      randomized clinical trials (RCTs) and pragmatic RCTs seem to be suitable options
      to address these critical knowledge gaps. Future trials have to consider greater
      representation of very old adults, women, underrepresented minorities, and
      individuals of differing health, cognitive, socioeconomic, and educational
      backgrounds. Feasibility analyses from existing large healthcare networks confirm
      appropriate power for death and cardiovascular outcomes for future RCTs in this
      area. CONCLUSION: Existing data cannot address uncertainties about the benefits
      and harms of statins for primary ASCVD prevention in adults aged 75 and older,
      especially those with comorbidities, frailty, and cognitive impairment. Evidence
      from 1 or more RCTs could address these important knowledge gaps to inform person
      centered decision-making. J Am Geriatr Soc 66:2188-2196, 2018.

PMID- 30277568
TI  - Root coverage procedures for treating localised and multiple recession-type
      defects.
AB  - BACKGROUND: Gingival recession is defined as the oral exposure of the root
      surface due to a displacement of the gingival margin apical to the cemento-enamel
      junction and it is regularly linked to the deterioration of dental aesthetics.
      Successful treatment of recession-type defects is based on the use of predictable
      root coverage periodontal plastic surgery (RCPPS) procedures. This review is an
      update of the original version that was published in 2009. OBJECTIVES: To
      evaluate the efficacy of different root coverage procedures in the treatment of
      single and multiple recession-type defects. SEARCH METHODS: Cochrane Oral
      Health's Information Specialist searched the following databases: Cochrane Oral
      Health's Trials Register (to 15 January 2018), the Cochrane Central Register of
      Controlled Trials (CENTRAL; 2017, Issue 12) in the Cochrane Library (searched 15
      January 2018), MEDLINE Ovid (1946 to 15 January 2018), and Embase Ovid (1980 to
      15 January 2018). The US National Institutes of Health Ongoing Trials Register
      (ClinicalTrials.gov) and the World Health Organization International Clinical
      Trials Registry Platform were searched for ongoing trials (15 January 2018). No
      restrictions were placed on the language or date of publication when searching
      the electronic databases. SELECTION CRITERIA: We included randomised controlled
      trials (RCTs) only of at least 6 months' duration evaluating recession areas
      (Miller's Class I or II >= 3 mm) and treated by means of RCPPS procedures. DATA
      COLLECTION AND ANALYSIS: Screening of eligible studies, data extraction and risk
      of bias assessment were conducted independently and in duplicate. Authors were
      contacted for any missing information. We expressed results as random-effects
      models using mean differences (MD) for continuous outcomes and odds ratios (OR)
      for dichotomous outcomes with 95% confidence intervals (CI). We used GRADE
      methods to assess the quality of the body of evidence of our main comparisons.
      MAIN RESULTS: We included 48 RCTs in the review. Of these, we assessed one as at
      low risk of bias, 12 as at high risk of bias and 35 as at unclear risk of bias.
      The results indicated a greater reduction in gingival recession for subepithelial
      connective tissue grafts (SCTG) + coronally advanced flap (CAF) compared to
      guided tissue regeneration with resorbable membranes (GTR rm) + CAF (MD -0.37 mm;
      95% CI -0.60 to -0.13, P = 0.002; 3 studies; 98 participants; low-quality
      evidence). There was insufficient evidence of a difference in gingival recession
      reduction between acellular dermal matrix grafts (ADMG) + CAF and SCTG + CAF or
      between enamel matrix protein (EMP) + CAF and SCTG + CAF. Regarding clinical
      attachment level changes, GTR rm + CAF promoted additional gains compared to SCTG
      + CAF (MD 0.35; 95% CI 0.06 to 0.63, P = 0.02; 3 studies; 98 participants; low
      quality evidence) but there was insufficient evidence of a difference between
      ADMG + CAF and SCTG + CAF or between EMP + CAF and SCTG + CAF. Greater gains in
      the keratinized tissue were found for SCTG + CAF when compared to EMP + CAF (MD 
      1.06 mm; 95% CI -1.36 to -0.76, P < 0.00001; 2 studies; 62 participants; low
      quality evidence), and SCTG + CAF when compared to GTR rm + CAF (MD -1.77 mm; 95%
      CI -2.66 to -0.89, P < 0.0001; 3 studies; 98 participants; very low-quality
      evidence). There was insufficient evidence of a difference in keratinized tissue
      gain between ADMG + CAF and SCTG + CAF. Few data exist on aesthetic condition
      change related to patients' opinion and patients' preference for a specific
      procedure. AUTHORS' CONCLUSIONS: Subepithelial connective tissue grafts,
      coronally advanced flap alone or associated with other biomaterial and guided
      tissue regeneration may be used as root coverage procedures for treating
      localised or multiple recession-type defects. The available evidence base
      indicates that in cases where both root coverage and gain in the width of
      keratinized tissue are expected, the use of subepithelial connective tissue
      grafts shows a slight improvement in outcome. There is also some weak evidence
      suggesting that acellular dermal matrix grafts appear as the soft tissue
      substitute that may provide the most similar outcomes to those achieved by
      subepithelial connective tissue grafts. RCTs are necessary to identify possible
      factors associated with the prognosis of each RCPPS procedure. The potential
      impact of bias on these outcomes is unclear.

PMID- 30277569
TI  - Effect of radiotherapy for rectal cancer on ovarian androgen production.

PMID- 30277570
TI  - NLRP3 inflammasome activation contributes to the pathogenesis of rheumatoid
      arthritis.
AB  - Nucleotide-binding, oligomerization domain (NOD)-like receptor family, pyrin
      domain containing 3 (NLRP3) gene polymorphism was reported to be associated with
      susceptibility, disease activity or anti-tumour necrosis factor (TNF) treatment
      response in rheumatoid arthritis (RA). However, the roles of NLRP3 inflammasome
      in the development of RA have not yet been elucidated fully. The present study
      aimed to study the role of NLRP3 inflammasome in RA. NLRP3 inflammasome
      activation in synovial tissues from RA and osteoarthritis (OA) patients were
      assessed by Western blot. Active caspase-1 in synovia was stained by a FAM-FLICA
      caspase-1 probe. Mice with collagen-induced arthritis (CIA) were treated with
      MCC950, a selective NLRP3 inhibitor, or vehicle for 2 weeks. The clinical score
      of arthritis, synovial inflammation and cartilage erosion were assessed.
      Proinflammatory cytokines were measured by enzyme-linked immunosorbent assay
      (ELISA). The results showed that NLRP3 inflammasome was highly activated in both
      synovia from RA patients and CIA mice. Activation of NLRP3 inflammasome occurred
      mainly in the infiltrating monocyte/macrophages in synovia, but not in fibroblast
      like synoviocytes. Treatment with MCC950 resulted in significantly less severe
      joints inflammation and bone destruction. NLRP3 inflammasome activation in the
      synovia was inhibited significantly by MCC950 with reduced production of
      interleukin (IL)-1beta. The inhibition of NLRP3 inflammasome activation by MCC950
      was confirmed further in a human monocytic cell line, THP-1. In conclusion, NLRP3
      inflammasome is involved in the pathogenesis of RA. Targeting NLRP3 inflammasome
      with a small molecule inhibitor might be a novel therapeutic strategy for RA.

PMID- 30277571
TI  - Burden of Restricted Activity and Associated Symptoms and Problems in Late Life
      and at the End of Life.
AB  - OBJECTIVES: To compare rates of restricted activity and associated symptoms and
      problems in the last 6 months of life with those in the period before the last 6
      months of life. DESIGN: Prospective cohort study. SETTING: Greater New Haven,
      Connecticut. PARTICIPANTS: Community-living persons aged 70 and older (N=754).
      MEASUREMENTS: The occurrence of restricted activity (staying in bed for at least
      half the day or cutting down on usual activities) and 24 prespecified symptoms
      and problems leading to restricted activity was ascertained monthly for nearly 19
      years. RESULTS: Rates of restricted activity per 100 person-months were 36.5 in
      the last 6 months of life versus 16.1 in the period before the last 6 months of
      life (P<.001). Of 737 participants with 1 month or more of restricted activity,
      rates of restricting symptoms per 100 person-months of restricted activity ranged
      from 8.0 for frequent or painful urination to 65.6 for been fatigued, and rates
      of restricting problems ranged from 0.1 for problem with alcohol to 23.4 for been
      afraid of falling. Rates were significantly higher in the last 6 months of life
      than in the prior period for 13 of the 24 restricting symptoms and problems
      (P<.05), most notably for shortness of breath (38.6 vs 21.8), weakness (37.3 vs
      18.9), and confusion (31.2 vs 9.8). Mean (standard error) number of restricting
      symptoms and problems was significantly higher in the last 6 months of life (6.1
      (0.1)) than in the prior period (4.7 (0.03)) (P<.001). CONCLUSION: Rates of
      restricted activity and associated symptoms and problems are substantially
      greater in the last 6 months of life than in the period before the last 6 months
      of life. Enhanced palliative care strategies may be needed to diminish the burden
      of distressing symptoms and problems at the end of life.

PMID- 30277573
TI  - "Killin' Ain't a Forgivin' Sin".

PMID- 30277574
TI  - A reinforcement learning approach to personalized learning recommendation
      systems.
AB  - Personalized learning refers to instruction in which the pace of learning and the
      instructional approach are optimized for the needs of each learner. With the
      latest advances in information technology and data science, personalized learning
      is becoming possible for anyone with a personal computer, supported by a data
      driven recommendation system that automatically schedules the learning sequence.
      The engine of such a recommendation system is a recommendation strategy that,
      based on data from other learners and the performance of the current learner,
      recommends suitable learning materials to optimize certain learning outcomes. A
      powerful engine achieves a balance between making the best possible
      recommendations based on the current knowledge and exploring new learning
      trajectories that may potentially pay off. Building such an engine is a
      challenging task. We formulate this problem within the Markov decision framework
      and propose a reinforcement learning approach to solving the problem.

PMID- 30277575
TI  - Moving beyond static survivorship care plans: A systems engineering approach to
      population health management for cancer survivors.
AB  - The American cancer survivor population is ever-growing, with necessary follow-up
      primarily accomplished in a high-touch fashion-adding to unsustainability and
      fragmentation of care. Given the complexities of the health care system processes
      needed to support survivorship, engineering approaches may best address
      performance deficits and facilitate the provision of patient-centered care. Such
      collaboration between health care and engineering is recommended for redesigning
      health care delivery systems. By using Systems Engineering Initiative for Patient
      Safety (SEIPS), a systems engineering model widely used to improve health care
      quality and delivery, the authors examine the work system to identify the
      barriers and facilitators to necessary care in the presence of a survivorship
      care plan and visit. Recommendations for future improvement include ensuring that
      care-planning processes are dynamic, clearly assigned, resilient, and integrated
      with electronic health record systems.

PMID- 30277576
TI  - GBGT1 is allelically diverse but dispensable in humans and naturally occurring
      anti-FORS1 shows an ABO-restricted pattern.
AB  - BACKGROUND: The FORS histo-blood group system was described in 2013 and much
      remains to be investigated regarding its genetic and immunohematologic
      characteristics, as well as its clinical importance. While presence of the
      c.887G>A-mutated GBGT1 gene, which results in FORS1 glycosphingolipid expression
      on human red blood cells (RBCs), is rare in the populations tested so far,
      naturally occurring anti-FORS1 in plasma appears common. STUDY DESIGN AND
      METHODS: The Erythrogene database was utilized to probe genetic variation in
      GBGT1 among 2504 individuals in the 1000 Genomes Project. We screened 1108
      Swedish blood donors for three principally important single-nucleotide
      polymorphisms (c.363C>A, c.886C>T, and c.887G>A) and selected samples were
      analyzed further. Screening for naturally occurring anti-FORS1 in plasma from 100
      donors was performed using antigen-positive RBCs. RESULTS: We identified 68 GBGT1
      alleles, of which three were previously listed blood group alleles. Eight
      potential null alleles were observed, based on three different nonsense
      mutations. Four healthy donors were found homozygous for c.363C>A, which
      truncates the GBGT1-encoded Fs synthase prematurely. This is the first
      description of human knock-outs for GBGT1. The c.886C>T mutation that alters the
      same codon (p.Arg296Trp) changed by c.887G>A (p.Arg296Gln) was overexpressed to
      investigate if it induces the FORS1+ phenotype. However, c.886C>T did not result
      in synthesis of FORS1. We detected anti-FORS1 in 10% of all donors tested but
      none in the A1 or A1B groups. CONCLUSION: We have extended the knowledge of GBGT1
      variants, allele frequencies, and the characteristics of naturally occurring
      antibodies in our newest carbohydrate blood group system, FORS. The finding of
      c.363C>A-homozygous donors indicates that GBGT1 is dispensable.

PMID- 30277572
TI  - Improving patient and caregiver outcomes in oncology: Team-based, timely, and
      targeted palliative care.
AB  - Over the past decade, a large body of evidence has accumulated supporting the
      integration of palliative care into oncology practice for patients with advanced
      cancer. The question is no longer whether palliative care should be offered, but
      what is the optimal model of delivery, when is the ideal time to refer, who is in
      greatest need of a referral, and how much palliative care should oncologists
      themselves be providing. These questions are particularly relevant given the
      scarcity of palliative care resources internationally. In this state-of-the
      science review directed at the practicing cancer clinician, the authors first
      discuss the contemporary literature examining the impact of specialist palliative
      care on various health outcomes. Then, conceptual models are provided to support
      team-based, timely, and targeted palliative care. Team-based palliative care
      allows the interdisciplinary members to address comprehensively the
      multidimensional care needs of patients and their caregivers. Timely palliative
      care, at its best, is preventive care to minimize crises at the end of life.
      Targeted palliative care involves identifying the patients most likely to benefit
      from specialist palliative care interventions, akin to the concept of targeted
      cancer therapies. Finally, the strengths and weaknesses of innovative care
      models, such as outpatient clinics, embedded clinics, nurse-led palliative care,
      primary palliative care provided by oncology teams, and automatic referral, are
      summarized. Moving forward, more research is needed to determine how different
      health systems can best personalize palliative care to provide the right level of
      intervention, for the right patient, in the right setting, at the right time. CA
      Cancer J Clin. 2018;680:00-00. 2018 American Cancer Society, Inc.

PMID- 30277577
TI  - Periodontal disease susceptible matrilines in the Cayo Santiago Macaca mulatta
      macaques.
AB  - OBJECTIVE AND BACKGROUND: The expression of periodontitis, including age of
      onset, extent, and severity is considered to represent an interaction of the
      individual's oral microbiome and host response to the microbial challenge that is
      modified by both genetics and environmental factors. The aim of this study was to
      determine the distribution of periodontitis in a population of nonhuman primates,
      to document features of familial distribution that could reflect heritability and
      transmission of microbes with enhanced virulence. MATERIAL AND METHODS: This
      report presents our findings from evaluation of periodontal disease bone defects
      in skulls from 569 animals (5-31 years of age) derived from the skeletons of the
      rhesus monkeys (Macaca mulatta) of Cayo Santiago derived from eight matrilines
      over 6-9 generations. The distance from the base of alveolar bone to the cemento
      enamel junction on 1st/2nd premolars and 1st/2nd molars from all four quadrants
      was evaluated as a measure of periodontal disease. Additionally, we documented
      the presence of periodontitis in 79 living descendants within these matrilines.
      RESULTS: The results demonstrated an increased extent and severity of
      periodontitis with aging across all matrilines. Extensive heterogeneity in
      disease expression was observed among the animals and this was linked to specific
      periodontitis susceptible matrilines. Moreover, we identified some matrilines in
      which the members appeared to show some resistance to more severe disease, even
      with aging. CONCLUSION: Linking these disease variations to multigenerational
      matriarchal family units supported familial susceptibility of periodontitis. This
      familial disease relationship was reinforced by the distribution of naturally
      occurring periodontitis in the living descendants.

PMID- 30277578
TI  - TRM4 is essential for cellulose deposition in Arabidopsis seed mucilage by
      maintaining cortical microtubule organization and interacting with CESA3.
AB  - The differentiation of the seed coat epidermal (SCE) cells in Arabidopsis
      thaliana leads to the production of a large amount of pectin-rich mucilage and a
      thick cellulosic secondary cell wall. The mechanisms by which cortical
      microtubules are involved in the formation of these pectinaceous and cellulosic
      cell walls are still largely unknown. Using a reverse genetic approach, we found
      that TONNEAU1 (TON1) recruiting motif 4 (TRM4) is implicated in cortical
      microtubule organization in SCE cells, and functions as a novel player in the
      establishment of mucilage structure. TRM4 is preferentially accumulated in the
      SCE cells at the stage of mucilage biosynthesis. The loss of TRM4 results in
      compact seed mucilage capsules, aberrant mucilage cellulosic structure, short
      cellulosic rays and disorganized cellulose microfibrils in mucilage. The defects
      could be rescued by transgene complementation of trm4 alleles. Probably, this is
      a consequence of a disrupted organization of cortical microtubules, observed
      using fluorescently tagged tubulin proteins in trm4 SCE cells. Furthermore, TRM4
      proteins co-aligned with microtubules and interacted directly with CELLULOSE
      SYNTHASE 3 in two independent assays. Together, the results indicate that TRM4 is
      essential for microtubule array organization and therefore correct cellulose
      orientation in the SCE cells, as well as the establishment of the subsequent
      mucilage architecture.

PMID- 30277579
TI  - Calcium supplementation during pregnancy for preventing hypertensive disorders
      and related problems.
AB  - BACKGROUND: Pre-eclampsia and eclampsia are common causes of serious morbidity
      and death. Calcium supplementation may reduce the risk of pre-eclampsia, and may
      help to prevent preterm birth. This is an update of a review last published in
      2014. OBJECTIVES: To assess the effects of calcium supplementation during
      pregnancy on hypertensive disorders of pregnancy and related maternal and child
      outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials
      Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry
      Platform (ICTRP) (18 September 2017), and reference lists of retrieved studies.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs), including
      cluster-randomised trials, comparing high-dose calcium supplementation (at least
      1 g daily of calcium) during pregnancy with placebo. For low-dose calcium we
      included quasi-randomised trials, trials without placebo, trials with
      cointerventions and dose comparison trials. DATA COLLECTION AND ANALYSIS: Two
      researchers independently assessed trials for inclusion and risk of bias,
      extracted data and checked them for accuracy. Two researchers assessed the
      evidence using the GRADE approach. MAIN RESULTS: We included 27 studies (18,064
      women). We assessed the included studies as being at low risk of bias, although
      bias was frequently difficult to assess due to poor reporting and inadequate
      information on methods.High-dose calcium supplementation (>= 1 g/day) versus
      placeboFourteen studies examined this comparison, however one study contributed
      no data. The 13 studies contributed data from 15,730 women to our meta-analyses.
      The average risk of high blood pressure (BP) was reduced with calcium
      supplementation compared with placebo (12 trials, 15,470 women: risk ratio (RR)
      0.65, 95% confidence interval (CI) 0.53 to 0.81; I2 = 74%). There was also a
      reduction in the risk of pre-eclampsia associated with calcium supplementation
      (13 trials, 15,730 women: average RR 0.45, 95% CI 0.31 to 0.65; I2 = 70%; low
      quality evidence). This effect was clear for women with low calcium diets (eight
      trials, 10,678 women: average RR 0.36, 95% CI 0.20 to 0.65; I2 = 76%) but not
      those with adequate calcium diets. The effect appeared to be greater for women at
      higher risk of pre-eclampsia, though this may be due to small-study effects (five
      trials, 587 women: average RR 0.22, 95% CI 0.12 to 0.42). These data should be
      interpreted with caution because of the possibility of small-study effects or
      publication bias. In the largest trial, the reduction in pre-eclampsia was modest
      (8%) and the CI included the possibility of no effect.The composite outcome
      maternal death or serious morbidity was reduced with calcium supplementation
      (four trials, 9732 women; RR 0.80, 95% CI 0.66 to 0.98). Maternal deaths were no
      different (one trial of 8312 women: one death in the calcium group versus six in
      the placebo group). There was an anomalous increase in the risk of HELLP syndrome
      in the calcium group (two trials, 12,901 women: RR 2.67, 95% CI 1.05 to 6.82,
      high-quality evidence), however, the absolute number of events was low (16 versus
      six).The average risk of preterm birth was reduced in the calcium supplementation
      group (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97; I2 = 60%; low
      quality evidence); this reduction was greatest amongst women at higher risk of
      developing pre-eclampsia (four trials, 568 women: average RR 0.45, 95% CI 0.24 to
      0.83; I2 = 60%). Again, these data should be interpreted with caution because of
      the possibility of small-study effects or publication bias. There was no clear
      effect on admission to neonatal intensive care. There was also no clear effect on
      the risk of stillbirth or infant death before discharge from hospital (11 trials,
      15,665 babies: RR 0.90, 95% CI 0.74 to 1.09).One study showed a reduction in
      childhood systolic BP greater than 95th percentile among children exposed to
      calcium supplementation in utero (514 children: RR 0.59, 95% CI 0.39 to 0.91). In
      a subset of these children, dental caries at 12 years old was also reduced (195
      children, RR 0.73, 95% CI 0.62 to 0.87).Low-dose calcium supplementation (< 1
      g/day) versus placebo or no treatmentTwelve trials (2334 women) evaluated low
      dose (usually 500 mg daily) supplementation with calcium alone (four trials) or
      in association with vitamin D (five trials), linoleic acid (two trials), or
      antioxidants (one trial). Most studies recruited women at high risk for pre
      eclampsia, and were at high risk of bias, thus the results should be interpreted
      with caution. Supplementation with low doses of calcium reduced the risk of pre
      eclampsia (nine trials, 2234 women: RR 0.38, 95% CI 0.28 to 0.52). There was also
      a reduction in high BP (five trials, 665 women: RR 0.53, 95% CI 0.38 to 0.74),
      admission to neonatal intensive care unit (one trial, 422 women, RR 0.44, 95% CI
      0.20 to 0.99), but not preterm birth (six trials, 1290 women, average RR 0.83,
      95% CI 0.34 to 2.03), or stillbirth or death before discharge (five trials, 1025
      babies, RR 0.48, 95% CI 0.14 to 1.67).High-dose (=/> 1 g) versus low-dose (< 1 g)
      calcium supplementationWe included one trial with 262 women, the results of which
      should be interpreted with caution due to unclear risk of bias. Risk of pre
      eclampsia appeared to be reduced in the high-dose group (RR 0.42, 95% CI 0.18 to
      0.96). No other differences were found (preterm birth: RR 0.31, 95% CI 0.09 to
      1.08; eclampsia: RR 0.32, 95% CI 0.07 to 1.53; stillbirth: RR 0.48, 95% CI 0.13
      to 1.83). AUTHORS' CONCLUSIONS: High-dose calcium supplementation (>= 1 g/day)
      may reduce the risk of pre-eclampsia and preterm birth, particularly for women
      with low calcium diets (low-quality evidence). The treatment effect may be
      overestimated due to small-study effects or publication bias. It reduces the
      occurrence of the composite outcome 'maternal death or serious morbidity', but
      not stillbirth or neonatal high care admission. There was an increased risk of
      HELLP syndrome with calcium supplementation, which was small in absolute
      numbers.The limited evidence on low-dose calcium supplementation suggests a
      reduction in pre-eclampsia, hypertension and admission to neonatal high care, but
      needs to be confirmed by larger, high-quality trials.

PMID- 30277580
TI  - Responses of MAC-T Cells to Inhibited Stearoyl-CoA Desaturase 1 during cis-9,
      trans-11 Conjugated Linoleic Acid Synthesis.
AB  - Cis-9-conjugated, trans-11-conjugated linoleic acid (CLA) is known for its
      positive activities on human health. The synthesis of cis-9, trans-11 CLA in
      mammary glands is generally thought to be catalyzed by stearoyl-CoA desaturase 1
      (SCD1), but this has not been rigorously established. In this study, we
      hypothesized that the inhibition of SCD1 (by CAY10566) would block the synthesis
      of cis-9, trans-11 CLA in bovine mammary alveolar cells (MAC-T) cells. Results
      showed that MAC-T cells incubated with 10 nM CAY10566 for 12 h (CAY) produced
      less cis-9, trans-11 CLA (p < 0.01), lower 14:1/(14:1 + 14:0)% (p < 0.01), more
      trans-11 18:1 (TVA) accumulation (p < 0.01), and reduced SCD1 mRNA levels (p <
      0.01) compared with the control group (CON). Moreover, the mRNA abundances of
      sterol regulatory element-binding protein 1 [SREBPF1], acyl-CoA synthetase short
      chain family member 2 [ACSS2], and lipin 1 [LPIN1] were significantly elevated
      when SCD1 was inhibited in the CAY group (p < 0.05). Taken together, CAY10566
      inhibition of SCD1 resulted in lower cis-9, trans-11 CLA synthesis ability, and
      SREBF1, ACSSS2, and LPIN1 were negatively associated with SCD1. These findings
      not only provide the direct evidence that cis-9, trans-11 CLA synthesis is
      catalyzed by SCD1, but also help us understand the responses of MAC-T cells to
      SCD1 inhibition.

PMID- 30277581
TI  - Racial Differences in Cause-Specific Mortality Between Community-Dwelling Older
      Black and White Adults.
AB  - OBJECTIVES: To understand which causes of death are higher in black than white
      community-dwelling older adults and determine whether differences in baseline
      risk factors explain racial differences in mortality. DESIGN: Longitudinal cohort
      study (Health, Aging, and Body Composition Study). SETTING: Pittsburgh,
      Pennsylvania; and Memphis, Tennessee. PARTICIPANTS: Black and white men and women
      aged 70 to 79 during recruitment (N=3,075; 48% men, 42% black) followed for a
      median of 13 years. MEASUREMENTS: A committee of physicians adjudicated cause of
      death, which was categorized as cardiovascular disease (CVD), stroke, cancer,
      dementia, pulmonary, infection, kidney, or other causes. Using competing risks
      regression, we examined whether known risk factors at baseline (demographic
      characteristics, smoking, body mass index, chronic diseases, physical function,
      cognition) could explain racial differences in cause-specific mortality risk.
      RESULTS: During follow-up, 1,991 (65%) participants died. Black participants died
      at higher rates from cancer (hazard ratio (HR)=1.36, 95% confidence interval
      (CI)=1.14-1.63), kidney disease (HR=2.09, 95% CI=1.16-3.74), stroke (HR=1.31, 95%
      CI=0.98-1.76); and CVD (HR=1.16, 95% CI=0.98-1.37). Poorer physical and cognitive
      performance at baseline among black participants explained most of the racial
      difference in risks of dying from kidney disease, stroke, and CVD but not cancer.
      When examining types of cancer deaths, black participants died at higher rates
      from multiple myeloma, pancreatic cancer, and prostate cancer, which baseline
      risk factors did not explain either. CONCLUSION: Factors contributing to poorer
      physical and cognitive performance in similarly aged black men and women could be
      targets to reduce excess mortality from CVD, stroke, and kidney disease. More
      work is needed to identify factors contributing to cancer mortality disparities.

PMID- 30277582
TI  - Long-term school-level effects of the Olweus Bullying Prevention Program (OBPP).
AB  - In agreement with two predictions, this somewhat unusual study documented that 70
      elementary schools (A-schools) with continued and repeated use of the Olweus
      Bullying Questionnaire (OBQ) in a four-year follow-up period of 2007-2010, two to
      eight years after original implementation of the Olweus Bullying Prevention
      Program (OBPP), had a clearly more favorable long-term development in terms of
      being-bullied problems, as measured with a completely independent data source,
      the National Pupil Survey than 102 comparable schools (B-schools) that had not
      conducted any OBQ-surveys in the same period. The odds of being bullied for
      students in a Norwegian average elementary school were also almost 40% higher
      than for students who attended a school with continued use of the OBQ, and very
      likely, other components of the program. Several alternative explanations of the
      findings were explored and found wanting. Results suggested that A-schools with
      continued use had changed their "school culture" for the better with regard to
      awareness, preparedness and competence in handling and preventing bullying. This
      form of 'organizational learning' has major consequences in that new groups of
      students will benefit from such a school environment. It was generally concluded 
      in spite of a highly stable average of the level of bullying problems in Norway 
      that it is fully possible to substantially reduce such problems not only in one
      year evaluations, as has been amply documented before, but also in the long term,
      up to eight years after original implementation, with a program such as the
      Olweus Bullying Prevention Program.

PMID- 30277583
TI  - Wnt/beta-catenin signaling cascade: A promising target for glioma therapy.
AB  - Glioma is one of the most treatment-refractory intracranial tumors, and the
      aberrant expressed Wnt/beta-catenin pathway is closely associated with glioma
      malignancy. In this regard, Wnt/beta-catenin signaling has been reported to play
      an essential role in cellular proliferation, migration, invasion, and
      angiogenesis, therefore contributing to glioma progression. However, the
      underlying mechanisms of Wnt/beta-catenin signaling involvement in gliomagenesis
      remain unknown. Here, we present an overview of the Wnt components and then go on
      to summarize the current knowledge describing the multitude of roles of Wnt/beta
      catenin in glioma, which are mediated by transcription factors, microRNAs, long
      noncoding RNAs, and so on. In the latter portion of the review, we elaborate the
      increasing apparent crosstalk of Wnt/beta-catenin pathway with PI3K/AKT signaling
      involved in these processes. Ultimately, compounds targeting the Wnt/beta-catenin
      are described in glioma. As better understanding of the regulatory mechanisms to
      glioma malignancies increases, Wnt/beta-catenin cascade may represent an area of
      developmental glioma therapeutics focus.

PMID- 30277584
TI  - Bayesian varying coefficient kernel machine regression to assess
      neurodevelopmental trajectories associated with exposure to complex mixtures.
AB  - Exposure to environmental mixtures can exert wide-ranging effects on child
      neurodevelopment. However, there is a lack of statistical methods that can
      accommodate the complex exposure-response relationship between mixtures and
      neurodevelopment while simultaneously estimating neurodevelopmental trajectories.
      We introduce Bayesian varying coefficient kernel machine regression (BVCKMR), a
      hierarchical model that estimates how mixture exposures at a given time point are
      associated with health outcome trajectories. The BVCKMR flexibly captures the
      exposure-response relationship, incorporates prior knowledge, and accounts for
      potentially nonlinear and nonadditive effects of individual exposures. This model
      assesses the directionality and relative importance of a mixture component on
      health outcome trajectories and predicts health effects for unobserved exposure
      profiles. Using contour plots and cross-sectional plots, BVCKMR also provides
      information about interactions between complex mixture components. The BVCKMR is
      applied to a subset of data from PROGRESS, a prospective birth cohort study in
      Mexico city on exposure to metal mixtures and temporal changes in
      neurodevelopment. The mixture include metals such as manganese, arsenic, cobalt,
      chromium, cesium, copper, lead, cadmium, and antimony. Results from a subset of
      Programming Research in Obesity, Growth, Environment and Social Stressors data
      provide evidence of significant positive associations between second trimester
      exposure to copper and Bayley Scales of Infant and Toddler Development cognition
      score at 24 months, and cognitive trajectories across 6-24 months. We also detect
      an interaction effect between second trimester copper and lead exposures for
      cognition at 24 months. In summary, BVCKMR provides a framework for estimating
      neurodevelopmental trajectories associated with exposure to complex mixtures.

PMID- 30277585
TI  - Distal-less homeobox 3, a negative regulator of myogenesis, is downregulated by
      microRNA-133.
AB  - Distal-less homeobox 3 (Dlx3), a member of the Dlx family of homeobox proteins,
      is a transcriptional activator of runt-related transcription factor 2 (Runx2)
      during osteogenic differentiation. It has been demonstrated that forced
      expression of Runx2 induces an osteogenic program and ectopic calcification in
      muscles. Therefore, it would be reasonable to predict that Dlx3 also affects
      myogenic differentiation. The relationship between Dlx3 and myogenesis, however,
      remains poorly understood. Therefore, in this study, the role and regulation of
      Dlx3 during myogenic differentiation were investigated. Expression level of Dlx3
      was downregulated in human mesenchymal stem cells (MSCs), mouse MSCs, and C2C12
      cells cultured in myogenic medium. Dlx3 level was inversely correlated with
      myogenic differentiation 1 and the muscle-specific microRNA, microRNA-133 (miR
      133). The expression level of Runx2 was closely regulated by Dlx3 even under
      myogenic conditions. Overexpression of Dlx3 markedly downregulated expression
      levels of myogenic transcription factors and myotube formation in C2C12 cells,
      whereas Dlx3 knockdown enhanced myogenic differentiation. The Dlx3 3'
      untranslated region (3'-UTR) has two potential binding sites for miR-133.
      Luciferase reporter assays demonstrated that Dlx3 is a direct target of miR-133a
      and miR-133b, and that the two target sites are redundantly active. Taken
      together, these results suggest that Dlx3 is a negative regulator of myogenic
      differentiation and that miR-133a and miR-133b enhance myogenic differentiation,
      partly through inhibition of Dlx3 expression via direct targeting of the Dlx3 3'
      UTR.

PMID- 30277587
TI  - Dietary Nondigestible Polysaccharides Ameliorate Colitis by Improving Gut
      Microbiota and CD4+ Differentiation, as Well as Facilitating M2 Macrophage
      Polarization.
AB  - BACKGROUND: The aim of this study was to investigate the therapeutic mechanism of
      a specific multifiber mix diet (MF) designed to match the fiber content of a
      healthy diet in interleukin-10 knockout (IL-10-/-) mice with spontaneous chronic
      colitis displaying similar characteristics to those of human Crohn's disease
      (CD). METHODS: Sixteen-week-old IL-10-/- mice were used for the experiments with
      MF diet for 4 weeks. Severity of colitis, the composition of the fecal
      microbiota, expression of Th1/Th17 cells, myeloperoxidase (MPO) concentrations,
      and inflammatory cytokines and chemokines (tumor necrosis factor-alpha [TNF
      alpha], IL-6, macrophage inflammatory protein [MIP]-2, monocyte chemoattractant
      protein-1 [MCP-1], and MIP-1alpha), as well as arginase 1 (Arg1) and signal
      transducers and activators of transcription 6 (STAT6) proteins, were measured at
      the end of the experiment. In addition, the corresponding metabolites (short
      chain fatty acids) of MF on CD4+CD25+Foxp3+ regulatory T cells (Tregs) were also
      detected in vivo and in vitro. RESULTS: MF treatment significantly ameliorated
      colitis associated with decreased lamina propria frequency of Th1/Th17 cells, MPO
      concentrations, and inflammatory cytokines and chemokines (TNF-alpha, IL-6, MIP
      2, MCP-1, and MIP-1alpha). An increase in gut microbial diversity was observed
      after MF treatment compared with IL-10-/- mice, including a significant increase
      in bacteria belonging to the Firmicutes phylum and a significant decrease in
      bacteria belonging to the Proteobacteria phylum. Moreover, MF treatment increased
      the differentiation of CD4+CD25+Foxp3+ Tregs mainly by microbial metabolites
      butyrate. In addition, Arg1 and STAT6 proteins were also significantly increased
      after MF treatment. CONCLUSIONS: These results shed light on the contribution of
      MF treatment to the CD mouse model and suggest that MF has potential as a
      therapeutic strategy for enhancing efficacy in inducing remission in patients
      with active CD.

PMID- 30277586
TI  - Recovery from acute lung injury can be regulated via modulation of regulatory T
      cells and Th17 cells.
AB  - Acute lung injury (ALI) is a severe inflammatory disease, for which no specific
      treatment exists. The decreased ratio of regulatory T cells (CD4+ CD25+ FoxP3
      Tregs) and Th17 cells is implicated in ALI and inflammation. We here investigated
      whether maintaining the balance of CD4+ CD25+ Foxp3+ Tregs and Th17 cells can
      alleviate lung injury. For CD4+ CD25+ FoxP3 Treg depletion, 200 MUg of an anti
      CD25 antibody was administered intraperitoneally per mouse on days -3 and -1
      before lipopolysaccharide (LPS) instillation. And 150 MUg of TGF-beta was
      administered intraperitoneally per mouse on day 0 after LPS instillation. To down
      regulate of Th17 cells, 200 MUg per mouse of isotype, IL-17 or IL-22 antibodies
      were injected intraperitoneally into mice at days 0 after LPS instillation. We
      detected lung morphology; lung wet-to-dry weight ratio; protein concentration,
      the count of total cells, neutrophils and macrophages, and cytokines in
      bronchoalveolar lavage fluid (BALF). And we also evaluated the percentage of CD4+
      CD25+ Foxp3+ Tregs in lung, and Th17 cells in lung. CD4+ CD25+ Foxp3+ Tregs
      depletion via anti-CD25 treatment or TGF-beta neutralization delayed recovery of
      ALI. The prolonged inflammation was mainly dominated by neutrophils, macrophages
      and Th17 cells. Furthermore, inhibition of Th17 cells via monoclonal antibodies
      against IL-17 and IL-22 alleviated ALI inflammation by inhibiting the recruitment
      of neutrophils and macrophages, increasing the number of CD4+ CD25+ Foxp3+ Tregs.
      Our findings support a critical role for CD4+ CD25+ Foxp3+ Tregs in regulating
      from ALI pathophysiology, and a potential therapeutic role for the inhibition of
      Th17 cells in ALI treatment. These findings provide a rationale for treating
      patients with ALI by modulating CD4+ CD25+ Foxp3+ Tregs and Th17 cells.

PMID- 30277589
TI  - 2-deoxy-D-glucose augments photodynamic therapy induced mitochondrial caspase
      independent apoptosis and energy-mediated autophagy.
AB  - OBJECTIVES: Compared to normal cells, malignant cells have a high degree of
      aerobic glycolysis, also known as the Warburg effect. Therefore, supplementing
      photodynamic therapy (PDT), an established cancer therapy, with metabolic
      inhibitors can augment the mitochondrial damage by depleting ATP. To assess the
      combined impact of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) and PDT on
      apoptosis and autophagy in human breast cancer cells, and examine the molecular
      basis. METHODS: Calcium-AM/PI double staining was used to evaluate cell
      viability. Reactive oxygen species (ROS), mitochondria membrane potential (MMP),
      nuclear morphology, and autophagosomes were measured using specific fluorescent
      markers. In addition, translocation of the apoptosis inducing factor (AIF) from
      the mitochondria to nucleus was imaged by confocal laser scanning microscopy, and
      DNA fragmentation was measured using PI staining and comet assay. PGC-1alpha
      expression, oxidative phosphorylation, ATP levels, and autophagy related proteins
      were detected by qRT-PCR, seahorse bioscience XFP extracellular flux analyzer,
      and Western blotting, respectively. RESULTS: Compared to with either monotherapy,
      2-DG+PDT resulted in significantly higher cytotoxicity in the three breast cancer
      cell lines (MDA-MB-231, MCF-7, and 4T1), which was consistent with tumor growth
      regression trends seen in the 4T1 xenograft model. A synergistic augmentation of
      mitochondrial dysfunction (in terms of ROS generation, MMP loss, and PGC-1alpha
      down-regulation) and ATP depletion was seen in cells receiving 2-DG and PDT. In
      addition, nuclear translocation of AIF and the subsequent DNA damage indicated
      that the cytotoxic effects were mediated by a caspase-independent mechanism,
      which was relieved by the ROS scavenger N-acetylcysteine. Autophagy via the AMP
      activated protein kinase (AMPK) was also observed following 2-DG+PDT, and
      reversed upon pre-treatment with the autophagy inhibitor 3-methyladenine.
      CONCLUSIONS: The anti-cancer effects of 2-DG+PDT are mediated by both
      mitochondria triggered apoptosis and AMPK-mediated autophagy. Lasers Surg. Med.
      (c) 2018 Wiley Periodicals, Inc.

PMID- 30277588
TI  - Simultaneous Alcohol and Marijuana Use Among Young Adult Drinkers: Age-Specific
      Changes in Prevalence from 1977 to 2016.
AB  - BACKGROUND: The overall prevalence of U.S. young adult alcohol use has decreased,
      but little is known about historical change in related behaviors such as
      simultaneous alcohol and marijuana (SAM) use that may increase alcohol-related
      risks and societal costs. The purpose of this paper was to examine historical
      change in SAM use prevalence among U.S. young adult alcohol users from 1977 to
      2016, and consider the extent to which observed historical change in SAM use
      among alcohol users reflects co-occurring change in marijuana use during these
      years. METHODS: Data on past 12-month alcohol, marijuana, and SAM use at up to 6
      modal ages (19/20, 21/22, 23/24, 25/26, 27/28, and 29/30) were collected from
      11,789 individuals (45.0% men) participating in the Monitoring the Future panel
      study. Annual prevalence estimates within modal age group were obtained;
      historical SAM use trends among alcohol and marijuana users were estimated.
      RESULTS: From 2014 to 2016, SAM use was reported by approximately 30% of alcohol
      users aged 19/20 and 21/22, and 20 to 25% of alcohol users aged 23/24 through
      29/30. Since the mid-1990s, age-specific historical trends in SAM use prevalence
      among alcohol users followed 1 of 4 patterns: significant increase followed by
      oscillating increases/decreases (at modal age 19/20), consistent and significant
      increases (at modal ages 21/22, 23/24, and 25/26), stability followed by increase
      (at modal ages 27/28), or stability (at modal ages 29/30). In contrast, SAM use
      trends among marijuana users primarily reflected stability, with some evidence of
      a decrease across time at modal ages 19/20 and 23/24. Historical change in SAM
      prevalence among alcohol users was strongly and positively correlated with
      changes in overall marijuana use prevalence. CONCLUSIONS: A growing proportion of
      early and mid-young adult alcohol users reported SAM use, with the highest risk
      among those in the early years of young adulthood. Young adult SAM use may
      continue to increase in proportion to the degree that young adult marijuana use
      continues to increase.

PMID- 30277590
TI  - RI-MP3 calculations of biomolecules based on the fragment molecular orbital
      method.
AB  - In this study, the third-order Moller-Plesset perturbation (MP3) theory using the
      resolution of the identity (RI) approximation was combined with the fragment
      molecular orbital (FMO) method to efficiently calculate a high-order electron
      correlation energy of biomolecular systems. We developed a new algorithm for the
      RI-MP3 calculation, which can be used with the FMO scheme. After test
      calculations using a small molecule, the FMO-RI-MP3 calculations were performed
      for two biomolecular systems comprising a protein and a ligand. The computational
      cost of these calculations was only around 5 and 4 times higher than those of the
      FMO-RHF calculations. The error associated with the RI approximation was around
      2.0% of the third-order correlation contribution to the total energy. However,
      the RI approximation error in the interaction energy between the protein and
      ligand molecule was insignificantly small, which reflected the negligible error
      in the inter fragment interaction energy. (c) 2018 Wiley Periodicals, Inc.

PMID- 30277591
TI  - Adaptive enrichment designs for confirmatory trials.
AB  - After an overview of the Food and Drugs Administration's 2012 draft guidance on
      enrichment strategies for clinical trials to support drug/biologic approval, we
      describe subsequent advances in adaptive enrichment designs in this direction. We
      also provide a concrete application in the enrichment design of the Diffusion and
      Perfusion Imaging Evaluation for Understanding Stroke Evolution 3 trial comparing
      a new endovascular treatment with standard of care for ischemic stroke patients.

PMID- 30277592
TI  - Excited-State Reactivity of [Mn(im)(CO)3 (phen)]+ : A Structural Exploration.
AB  - The electronic excited state reactivity of [Mn(im)(CO)3 (phen)]+ (phen = 1,10
      phenanthroline; im = imidazole) ranging between 420 and 330 nm have been analyzed
      by means of relativistic spin-orbit time-dependent density functional theory and
      wavefunction approaches (state-average-complete-active-space self-consistent
      field/multistate CAS second-order perturbation theory). Minimum energy conical
      intersection (MECI) structures and connecting pathways were explored using the
      artificial force induced reaction (AFIR) method. MECIs between the first and
      second singlet excited states (S1 /S2 -MECIs) were searched by the single
      component AFIR (SC-AFIR) algorithm combined with the gradient projection type
      optimizer. The structural, electronic, and excited states properties of
      [Mn(im)(CO)3 (phen)]+ are compared to those of the Re(I) analogue [Re(im)(CO)3
      (phen)]+ . The high density of excited states and the presence of low-lying metal
      centered states that characterize the Mn complex add complexity to the
      photophysics and open various dissociative channels for both the CO and imidazole
      ligands. (c) 2018 Wiley Periodicals, Inc.

PMID- 30277593
TI  - Repeated injection of KMRC011, a medical countermeasure for radiation, can cause
      adverse health effects in cynomolgus monkeys.
AB  - High-dose radiation-induced tissue damage is a major limiting factor in the
      medical application of nuclear technology. Herein, we tested 28-day repeated-dose
      toxicity of KMRC011, an agonist of toll-like receptor (TLR) 5, which is being
      developed as a medical countermeasure for radiation, using cynomolgus monkeys.
      KMRC011 (0.01, 0.02 or 0.04 mg/kg/day) was intramuscularly injected once daily
      for 4 weeks, and each two monkeys in both control and 0.04 mg/kg/day group were
      observed for an additional 2-week recovery period. There were no dose-related
      toxicological changes in mortality, clinical observations, body weight, food
      consumption, ophthalmological findings, electrocardiographs, coagulation, serum
      chemistry, organ weights, or urinalysis and urine chemistry. Although treatment
      related changes, such as increased white blood cells, increased absolute and
      relative neutrophils, decreased relative lymphocytes and inflammatory lesions,
      were noted in the maximum dose group, these findings were not observed after the
      2-week recovery period. Further, we considered that the kidneys and heart may be
      target organs of TLR5 agonists, as well as the spleen, and that autophagic
      signals can be triggered in tissue damage and the repair process. Importantly,
      accumulation of p62 protein, an indicator of autophagy, and a decrease of
      caveolin-1 protein, a regulator of TLR5 protein half-life, were found in both
      tissues from the highest dose group. Therefore, we conclude that the no-observed
      adverse-effect level for KMRC011 may be greater than 0.04 mg/kg/day in male and
      female monkeys. Additionally, we propose that further studies are needed to
      identify the molecular signals, which are related to KMRC011-induced adverse
      effects.

PMID- 30277594
TI  - Revisit of large-gap Si16 clusters encapsulating group-IV metal atoms (Ti, Zr,
      Hf).
AB  - Doped clusters by Si16 cage encapsulating group-IV metal atoms (M@Si16 , M = Ti,
      Zr and Hf) are computationally investigated by both density functional theory
      (DFT) and high-level CCSD(T) method. Their low-energy structures are globally
      searched using a genetic algorithm based on DFT. The ground state structures of
      neutral and anionic M@Si16 are determined by calculating the vertical and
      adiabatic detachment energies and comparing them with the experimental data. For
      neutral Ti@Si16 , the Frank-Kasper (FK) deltahedron with T d symmetry and
      distorted FK isomer with C3v symmetry are nearly degenerate as the ground state
      and may coexist in laboratory, while the distorted FK isomer is the most probable
      structure for Ti@Si16 - anion. For neutral and anionic Zr@Si16 and Hf@Si16
      clusters, the ground states at finite temperatures up to 300 K are the fullerene
      like D 4d bitruncated square trapezohedron. These theoretical results establish a
      more complete picture for the most stable structures of M@Si16 clusters, which
      possess large gaps and may serve as building blocks for electronic and
      optoelectronic applications.

PMID- 30277595
TI  - Association between chronic viral hepatitis and metabolic syndrome in southern
      Taiwan: a large population-based study.
AB  - BACKGROUND: The impact of metabolic syndrome (MetS) on hepatitis is an
      interesting issue. AIM: To evaluate the association of MetS and chronic viral
      hepatitis including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection
      in southern Taiwan. METHODS: From 2004 to 2013, a series of community-based
      health screenings for residents aged 40 and older were held in Tainan city. MetS
      was defined according to the Joint Scientific Statement. Cut-offs of body-mass
      index measures of 24 kg/m2 and 27 kg/m2 were used to stratify lean, overweight
      and obese subjects. RESULTS: We enrolled 180 359 participants; the prevalence of
      MetS was 30.1%, which was significantly associated with advanced age and female
      sex. There were 18 726 (10.4%) HBV, 13 428 (7.4%) HCV, 1337 (0.7%) HBV plus HCV
      (B+C) and 146 868 (81.5%) non-HBV non-HCV participants (NBNC). Prevalence rates
      of MetS in subjects with HBV, HCV, B+C and NBNC were 25.2%, 31.5%, 28.9% and
      30.7% respectively (P < 0.001). There were 18.8% lean body, 35.4% overweight and
      45.8% obese participants among 54 361 MetS subjects. Lean MetS subjects were
      older, had more diabetes, and had higher metabolic component levels, but lower
      alanine transaminase and aspartate transaminase-platelet ratio index levels
      compared with obese MetS subjects. HCV infection was positively associated with
      MetS (P < 0.001). However, HBV infection was inversely associated with MetS only
      among lean subjects (P = 0.002), but not among the general population.
      CONCLUSIONS: This large population-based study indicated that HCV infection was
      positively associated with MetS. However, HBV infection was inversely associated
      with MetS only among lean subjects.

PMID- 30277596
TI  - KDM6B promotes ovarian cancer cell migration and invasion by induced transforming
      growth factor-beta1 expression.
AB  - KDM6B, also known as JMJD3, is a member of the family of histone lysine
      demethylase (KDMs), which is closely related to many types of cancers. However,
      its role and the underlying mechanisms in ovarian cancer remain unknown. Here we
      show that KDM6B is elevated in epithelial ovarian cancer and its expression level
      is closely related with metastasis and invasion. In addition, survival analysis
      showed that high expression of KDM6B was associated with low overall survival in
      ovarian cancer patients. Overexpression of KDM6B in epithelial ovarian cancer
      cells promoted proliferation, epithelial-mesenchymal transition (EMT), migration
      and invasion in vitro, and enhanced metastatic capacities in vivo. On the
      contrary, silencing KDM6B in invasive and metastatic ovarian cancer cells
      inhibited these processes. Mechanistically, we found that KDM6B exerts its
      function by modulating the transforming growth factor-beta1 (TGF-beta1)
      expression, and TGF-beta1 signal pathway inhibitor LY2157299 significantly
      inhibited KDM6B-induced proliferation, migration, metastasis, and EMT in ovarian
      cancer cells. Our findings, for the first time, reveal the pivotal role of KDM6B
      in the invasion and metastatic behavior of epithelial ovarian cancer. Thus,
      targeting KDM6B may be a useful strategy to interfere with these behaviors of
      epithelial ovarian cancer.

PMID- 30277597
TI  - Expression of exosomal microRNAs during chondrogenic differentiation of human
      bone mesenchymal stem cells.
AB  - The aim of the current study was to compare the expression of microRNAs (miRNAs)
      in exosomes derived from human bone mesenchymal stem cells (hBMSCs) with and
      without chondrogenic induction. Exosomes derived from hBMSCs were isolated and
      identified. Microarray analysis was performed to compare miRNA expression between
      exosomes derived from hBMSCs with and without chondrogenic induction, and
      quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the
      differentially expressed miRNAs. hBMSCs were transfected with miRNA mimic to
      extract miRNA-overexpressed exosomes. The results showed that most exosomes
      exhibited a cup-shaped or round-shaped morphology with a diameter of
      approximately 50-200 nm and expressed CD9 and CD63. We detected 141 miRNAs that
      were differentially expressed with and without chondrogenic induction by over a
      twofold change, including 35 upregulated miRNAs, such as miR-1246, miR-1290, miR
      193a-5p, miR-320c, and miR-92a, and 106 downregulated miRNAs, such as miR-377-3p
      and miR-6891-5p. qRT-PCR analysis validated these results. Exosomes derived from
      hBMSCs overexpressing miR-320c were more efficient than normal exosomes derived
      from control hBMSCs at promoting osteoarthritis chondrocyte proliferation, down
      regulated matrix metallopeptidase 13 and up-regulated (sex determining region Y)
      box 9 expression during hBMSC chondrogenic differentiation. In conclusion, we
      identified a group of upregulated miRNAs in exosomes derived from hBMSCs with
      chondrogenic induction that may play an important role in mesenchymal stem cell
      derived exosomes in cartilage regeneration and, ultimately, the treatment of
      arthritis. We demonstrated the potential of these modified exosomes in the
      development of novel therapeutic strategies.

PMID- 30277598
TI  - Functional characterization of the Sox2, c-Myc, and Oct4 promoters.
AB  - To better understand the mechanisms in transcriptional regulation, we analyzed
      the promoters of the reprogramming key genes Sox2, c-Myc, and Oct4. Here, we
      cloned different 5' deletions of the goat Sox2, c-Myc, and Oct4 promoters, and
      evaluated their functions by green fluorescent protein reporter system and dual
      luciferase reporter system. Site-directed mugagenesis and epigenetic modifiers
      were used to explore the influence of transcription binding sites and epigenetic
      status on the promoters. The results suggested that the basal promoters were
      located in the - 109 to 49, - 147 to 1, and - 96 to 30 bp regions of the Sox2, c
      Myc, and Oct4 promoters. The transcription factors that identified to influence
      the Sox2, c-Myc, and Oct4 promoter activities were Elf-1 and activating protein 2
      (AP-2), C/EBP and Sp1, and Mzf1 and Sp1, respectively. The epigenetic alternation
      of the Sox2, c-Myc, and Oct4 promoters by 5-aza-2'-deoxycytidine or/and
      trichostatin A significantly increased the promoter activities. In conclusion,
      the result determined the core promoter areas of the Sox2, c-Myc, and Oct4 genes,
      and identified the transcription factors that influence their promoter
      activities. We also verified that the Sox2, c-Myc, and Oct4 promoters were
      hypermethylated and hypoacetylated.

PMID- 30277599
TI  - CCL17 exerts a neuroimmune modulatory function and is expressed in hippocampal
      neurons.
AB  - Chemokines are important signaling molecules in the immune and nervous system.
      Using a fluorescence reporter mouse model, we demonstrate that the chemokine
      CCL17, a ligand of the chemokine receptor CCR4, is produced in the murine brain,
      particularly in a subset of hippocampal CA1 neurons. We found that basal
      expression of Ccl17 in hippocampal neurons was strongly enhanced by peripheral
      challenge with lipopolysaccharide (LPS). LPS-mediated induction of Ccl17 in the
      hippocampus was dependent on local tumor necrosis factor (TNF) signaling, whereas
      upregulation of Ccl22 required granulocyte-macrophage colony-stimulating factor
      (GM-CSF). CCL17 deficiency resulted in a diminished microglia density under
      homeostatic and inflammatory conditions. Further, microglia from naive Ccl17
      deficient mice possessed a reduced cellular volume and a more polarized process
      tree as assessed by computer-assisted imaging analysis. Regarding the overall
      branching, cell surface area, and total tree length, the morphology of microglia
      from naive Ccl17-deficient mice resembled that of microglia from wild-type mice
      after LPS stimulation. In line, electrophysiological recordings indicated that
      CCL17 downmodulates basal synaptic transmission at CA3-CA1 Schaffer collaterals
      in acute slices from naive but not LPS-treated animals. Taken together, our data
      identify CCL17 as a homeostatic and inducible neuromodulatory chemokine affecting
      the presence and morphology of microglia and synaptic transmission in the
      hippocampus.

PMID- 30277600
TI  - Effect of simvastatin in different concentrations on free radicals in A-2058
      human melanoma malignum cells-EPR studies.
AB  - The influence of concentration of simvastatin (SIM) on free radicals in A-2058
      human melanoma malignum cells was studied. The proliferation assay for melanoma A
      2058 cells with SIM in concentration range from 0.1 to 20 uM was performed. SIM
      in the concentrations of 0.1, 0.3, and 1 MUM only slightly changed the growth of
      A-2058 cells, but the growth of the cells considerably decreased for higher
      concentrations of SIM. Free radicals in the cells were examined by an X-band (9.3
      GHz) electron paramagnetic resonance (EPR) spectroscopy. o-Semiquinone free
      radicals with g-factors in the range of 2.0060 to 2.0065 were found in A-2058
      cells. The asymmetric broad EPR spectra with linewidths (DeltaBpp) from 0.87 to
      1.25 mT were measured. The fast spin-lattice relaxation processes characterized
      all the tested cells. The free radical concentrations in the all A-2058 cells
      cultured with SIM were lower than in the control cells. The quenching of free
      radicals in A-2058 cells depended on concentration of SIM. This effect was the
      weakest for concentration of SIM of 3 MUM. The strongest decrease of free radical
      concentration caused SIM in concentration of 1 MUM.

PMID- 30277601
TI  - The Impact of Parental and Medical Leave Policies on Socioeconomic and Health
      Outcomes in OECD Countries: A Systematic Review of the Empirical Literature.
AB  - : Policy Points: Historically, reforms that have increased the duration of job
      protected paid parental leave have improved women's economic outcomes. By
      targeting the period around childbirth, access to paid parental leave also
      appears to reduce rates of infant mortality, with breastfeeding representing one
      potential mechanism. The provision of more generous paid leave entitlements in
      countries that offer unpaid or short durations of paid leave could help families
      strike a balance between the competing demands of earning income and attending to
      personal and family well-being. CONTEXT: Policies legislating paid leave from
      work for new parents, and to attend to individual and family illness, are common
      across Organisation for Economic Co-operation and Development (OECD) countries.
      However, there exists no comprehensive review of their potential impacts on
      economic, social, and health outcomes. METHODS: We conducted a systematic review
      of the peer-reviewed literature on paid leave and socioeconomic and health
      outcomes. We reviewed 5,538 abstracts and selected 85 published papers on the
      impact of parental leave policies, 22 papers on the impact of medical leave
      policies, and 2 papers that evaluated both types of policies. We synthesized the
      main findings through a narrative description; a meta-analysis was precluded by
      heterogeneity in policy attributes, policy changes, outcomes, and study designs.
      FINDINGS: We were able to draw several conclusions about the impact of parental
      leave policies. First, extensions in the duration of paid parental leave to
      between 6 and 12 months were accompanied by attendant increases in leave-taking
      and longer durations of leave. Second, there was little evidence that extending
      the duration of paid leave had negative employment or economic consequences.
      Third, unpaid leave does not appear to confer the same benefits as paid leave.
      Fourth, from a population health perspective, increases in paid parental leave
      were consistently associated with better infant and child health, particularly in
      terms of lower mortality rates. Fifth, paid paternal leave policies of adequate
      length and generosity have induced fathers to take additional time off from work
      following the birth of a child. How medical leave policies for personal or family
      illness influence health has not been widely studied. CONCLUSIONS: There is
      substantial quasi-experimental evidence to support expansions in the duration of
      job-protected paid parental leave as an instrument for supporting women's labor
      force participation, safeguarding women's incomes and earnings, and improving
      child survival. This has implications, in particular, for countries that offer
      shorter durations of job-protected paid leave or lack a national paid leave
      entitlement altogether.

PMID- 30277604
TI  - Toward Mass Production of CVD Graphene Films.
AB  - Chemical vapor deposition (CVD) is considered to be an efficient method for
      fabricating large-area and high-quality graphene films due to its excellent
      controllability and scalability. Great efforts have been made to control the
      growth of graphene to achieve large domain sizes, uniform layers, fast growth,
      and low synthesis temperatures. Some attempts have been made by both the
      scientific community and startup companies to mass produce graphene films;
      however, there is a large difference in the quality of graphene synthesized on a
      laboratory scale and an industrial scale. Here, recent progress toward the mass
      production of CVD graphene films is summarized, including the manufacturing
      process, equipment, and critical process parameters. Moreover, the large-scale
      homogeneity of graphene films and fast characterization methods are also
      discussed, which are crucial for quality control in mass production.

PMID- 30277602
TI  - Prokineticin-2 promotes chemotaxis and alternative A2 reactivity of astrocytes.
AB  - Astrocyte reactivity is disease- and stimulus-dependent, adopting either a
      proinflammatory A1 phenotype or a protective, anti-inflammatory A2 phenotype.
      Recently, we demonstrated, using cell culture, animal models and human brain
      samples, that dopaminergic neurons produce and secrete higher levels of the
      chemokine-like signaling protein Prokineticin-2 (PK2) as a compensatory
      protective response against neurotoxic stress. As astrocytes express a high level
      of PK2 receptors, herein, we systematically characterize the role of PK2 in
      astrocyte structural and functional properties. PK2 treatment greatly induced
      astrocyte migration, which was accompanied by a shift in mitochondrial energy
      metabolism, a reduction in proinflammatory factors, and an increase in the
      antioxidant genes Arginase-1 and Nrf2. Overexpression of PK2 in primary
      astrocytes or in the in vivo mouse brain induced the A2 astrocytic phenotype with
      upregulation of key protective genes and A2 reactivity markers including Arginase
      1 and Nrf2, PTX3, SPHK1, and TM4SF1. A small-molecule PK2 agonist, IS20, not only
      mimicked the protective effect of PK2 in primary cultures, but also increased
      glutamate uptake by upregulating GLAST. Notably, IS20 blocked not only MPTP
      induced reductions in the A2 phenotypic markers SPHK1 and SCL10a6 but also
      elevation of the of A1 marker GBP2. Collectively, our results reveal that PK2
      regulates a novel neuron-astrocyte signaling mechanism by promoting an
      alternative A2 protective phenotype in astrocytes, which could be exploited for
      development of novel therapeutic strategies for PD and other related chronic
      neurodegenerative diseases. PK2 signals through its receptors on astrocytes and
      promotes directed chemotaxis. PK2-induced astrocyte reactivity leads to an
      increase in antioxidant and anti-inflammatory proteins while increasing glutamate
      uptake, along with decreased inflammatory factors. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 30277605
TI  - Diphenylamine-Substituted Osmanaphthalyne Complexes: Structural, Bonding, and
      Redox Properties of Unusual Donor-Bridge-Acceptor Systems.
AB  - Diarylamine-substituted osmanaphthalyne complexes that feature two redox centers
      linked by the rigid skeleton of the metallacycle (C^C+ ), specifically, [OsCl2
      (PPh3 )2 {(C^C+ )NAr2 }][BF4 - ] (Ar=Ph (1 a), p-MeOPh (1 b)) and their open-ring
      precursors [OsHCl2 (PPh3 )2 {(=C-C(PPh3 + )=CHPh)NR2 }][BF4 - ] (Ar=Ph (2 a), p
      MeOPh (2 b)), were successfully synthesized and characterized by 1 H, 13 C, and
      31 P NMR spectroscopy, ESI-MS, and elemental analysis. The solid-state molecular
      structures of complexes 1 a and 2 a were ascertained by single-crystal X-ray
      diffraction. The Os=C bond length in both complexes 1 a and 2 a fell within the
      range reported for similar osmanaphthalynes and osmium carbyne complexes,
      respectively. The structural parameters determined for complex 1 a, which were
      successfully reproduced by theoretical calculations, point to a pi-delocalized
      metallacycle structure. The purple color of compounds 1 a and b was explained by
      the diarylamine->Os(metallacycle) charge-transfer absorption in the visible
      region. The neutral, one-electron-oxidized and one-electron-reduced states of
      compounds 1 a, b, and a reference complex that lacked the diarylamine
      substituent, [OsCl2 (PPh3 )2 {(C^C+ )}][BF4 - ] (1'), were investigated by cyclic
      and square-wave voltammetry, UV/Vis/NIR spectroelectrochemistry, and DFT
      calculations. The spin density in singly oxidized complexes [1 a]+ and [1 b]+
      predominantly resided on the aminyl segment, with osmium involvement controlled
      by the diphenylamine substitution. Spin density in stable, singly-reduced [1']-
      was distributed mainly over the osmanaphthalyne metallacycle.

PMID- 30277606
TI  - An In Situ Reversible Heterodimeric Nanoswitch Controlled by Metal-Ion-Ligand
      Coordination Regulates the Mechanosensing and Differentiation of Stem Cells.
AB  - In situ and cytocompatible nanoswitching by external stimuli is highly appealing
      for reversibly regulating cellular adhesion and functions in vivo. Here, a
      heterodimeric nanoswitch is designed to facilitate in situ switchable and
      combinatorial presentation of integrin-binding cell-adhesive moieties, such as
      Mg2+ and Arg-Gly-Asp (RGD) ligand in nanostructures. In situ reversible
      nanoswitching is controlled by convertible coordination between bioactive Mg2+
      and bisphosphonate (BP) ligand. A BP-coated gold-nanoparticle monomer (BP-AuNP)
      on a substrate is prepared to allow in situ assembly of cell-adhesive Mg2+ 
      active Mg-BP nanoparticles (NPs) on a BP-AuNP surface via Mg2+ -BP coordination,
      yielding heterodimeric nanostructures (switching "ON").
      Ethylenediaminetetraacetic acid (EDTA)-based Mg2+ chelation allows in situ
      disassembly of Mg2+ -BP NP, reverting to Mg2+ -free monomer (switching "OFF").
      This in situ reversible nanoswitching on and off of cell-adhesive Mg2+
      presentation allows reversible cell adhesion and release in vivo, respectively,
      and spatiotemporally controls cyclic cell adhesion. In situ heterodimeric
      assembly of dual RGD ligand- and Mg2+ -active RGD-BP-Mg2+ NP (switching "Dual
      ON") further tunes and promotes focal adhesion, spreading, and differentiation of
      stem cells. The modular nature of this in situ nanoswitch can accommodate various
      bioactive nanostructures via metal-ion-ligand coordination to regulate diverse
      cellular functions in vivo in reversible and compatible manner.

PMID- 30277603
TI  - Resting-state basal ganglia network codes a motor musical skill and its
      disruption From dystonia.
AB  - BACKGROUND: Musician's dystonia critically impacts professional musicians'
      careers as they may lose musical skills, which have been acquired through long
      and intensive training. Yet the pathophysiology of musician's dystonia and its
      link to the neural mechanisms supporting musical skills is poorly understood. We
      tested if resting-state functional connectivity might reflect an aspect of
      musical skill linked to the pathophysiology of musician's dystonia. We also
      tested a second hypothesis that the region with altered resting-state functional
      connectivity might be correlated with a quantitative measure of musical skills.
      METHODS: We studied 21 patients with musician's dystonia affecting their hands
      and 34 healthy musicians, using resting-state functional magnetic resonance
      imaging and behavioral assessment. We tested between-group differences of resting
      state functional connectivity throughout the whole brain using independent
      component analysis. RESULTS: We found abnormal basal ganglia resting-state
      functional connectivity in the putamina of patients with musician's dystonia
      compared with those of healthy musicians (P = 0.035 corrected for multiple
      comparisons). We also found that the temporal precision of keystrokes was
      correlated with basal ganglia functional connectivity in the putamina of healthy
      pianists (r = 0.72, P = 0.0005), but not in pianists with musician's dystonia (r
      = -0.11, P = 0.64). CONCLUSIONS: We show that abnormalities of the putamen exist
      even at rest in musician's dystonia, whereas putaminal abnormality has previously
      been reported during a task. Moreover, basal ganglia resting-state functional
      connectivity in the putamen represented training levels in healthy musicians, and
      its disruption was associated with musician's dystonia. This novel finding hints
      at the pathophysiological mechanisms by which musician's dystonia follows
      extensive musical training. (c) 2018 The Authors. Movement Disorders published by
      Wiley Periodicals, Inc. on behalf of International Parkinson and Movement
      Disorder Society.

PMID- 30277608
TI  - Compelling Rejuvenated Catalytic Performance in Metallic Glasses.
AB  - Metallic glasses (MGs) with the metastable nature and random atomic packing
      structure have attracted large attention in the catalytic family due to their
      superior catalytic performance. In contrast, their crystalline counterparts are
      restricted by the highly ordered packing structure, fewer surface active sites,
      and crystallographic defects for catalytic activity. The uncertainty of the
      different catalytic mechanisms and the intrinsic characteristics correlated to
      MGs and their crystalline counterparts become a major impediment to promote their
      catalytic efficiencies and widespread applications. Herein, it is reported that
      the excellent catalytic behavior in Fe-based MGs goes through a detrimental
      effect with the partial crystallization, but receives a compelling rejuvenation
      in the full crystallization. Further investigation reveals that multiphase
      intermetallics with electric potential differences in fully crystallized alloys
      facilitate the formation of galvanic cells. More importantly, extensively reduced
      grain boundaries due to grain growth greatly weaken electron trapping and promote
      inner electron transportation. The relatively homogenous grain-boundary corrosion
      in the intermetallics contributes to well-separated phases after reaction,
      leading to refreshment of the surface active sites, thereby quickly activating
      hydrogen peroxide and rapidly degrading organic pollutants. The exploration of
      catalytic mechanisms in the crystalline counterparts of MGs provides significant
      insights into revolutionize novel catalysts.

PMID- 30277607
TI  - Inhibition of hematopoietic cell kinase dysregulates microglial function and
      accelerates early stage Alzheimer's disease-like neuropathology.
AB  - Emerging evidence have posited that dysregulated microglia impair clearance and
      containment of amyloid-beta (Abeta) species in the brain, resulting in aberrant
      buildup of Abeta and onset of Alzheimer's disease (AD). Hematopoietic cell kinase
      (Hck) is one of the key regulators of phagocytosis among the Src family tyrosine
      kinases (SFKs) in myeloid cells, and its expression is found to be significantly
      altered in AD brains. However, the role of Hck signaling in AD pathogenesis is
      unknown. We employed pharmacological inhibition and genetic ablation of Hck in
      BV2 microglial cells and J20 mouse model of AD, respectively, to evaluate the
      impact of Hck deficiency on Abeta-stimulated microglial phagocytosis, Abeta
      clearance, and resultant AD-like neuropathology. Our in vitro data reveal that
      pharmacological inhibition of SFKs/Hck in BV2 cells and genetic ablation of their
      downstream kinase, spleen tyrosine kinase (Syk), in primary microglia
      significantly attenuate Abeta oligomers-stimulated microglial phagocytosis.
      Whereas in Hck-deficient J20 mice, we observed exacerbated Abeta plaque burden,
      reduced microglial coverage, containment, and phagocytosis of Abeta plaques, and
      induced iNOS expression in plaque-associated microglial clusters. These
      multifactorial changes in microglial activities led to attenuated PSD95 levels in
      hippocampal DG and CA3 regions, but did not alter the postsynaptic dendritic
      spine morphology at the CA1 region nor cognitive function of the mice. Hck
      inhibition thus accelerates early stage AD-like neuropathology by dysregulating
      microglial function and inducing neuroinflammation. Our data implicate that Hck
      pathway plays a prominent role in regulating microglial neuroprotective function
      during the early stage of AD development.

PMID- 30277609
TI  - A Cryogenic Process for Antisolvent-Free High-Performance Perovskite Solar Cells.
AB  - A cryogenic process is introduced to control the crystallization of perovskite
      layers, eliminating the need for the use of environmentally harmful antisolvents.
      This process enables decoupling of the nucleation and the crystallization phases
      by inhibiting chemical reactions in as-cast precursor films rapidly cooled down
      by immersion in liquid nitrogen. The cooling is followed by blow-drying with
      nitrogen gas, which induces uniform precipitation of precursors due to the
      supersaturation of precursors in the residual solvents at very low temperature,
      while at the same time enhancing the evaporation of the residual solvents and
      preventing the ordered precursors/perovskite from redissolving into the residual
      solvents. Using the proposed techniques, the crystallization process can be
      initiated after the formation of a uniform precursor seed layer. The process is
      generally applicable to improve the performance of solar cells using perovskite
      films with different compositions, as demonstrated on three different types of
      mixed halide perovskites. A champion power conversion efficiency (PCE) of 21.4%
      with open-circuit voltage (VOC ) = 1.14 V, short-circuit current density ( JSC )
      = 23.5 mA cm-2 , and fill factor (FF) = 0.80 is achieved using the proposed
      cryogenic process.

PMID- 30277611
TI  - Cucurbitacin I induces cancer cell death through the endoplasmic reticulum stress
      pathway.
AB  - Endoplasmic reticulum stress (ERS) is usually involved in tumor development and
      progression, and anticancer agents have recently been recognized to induce ERS.
      Cucurbitacin-I showed a potent anticancer action by inducing apoptosis through
      the inhibition of signal transducer and activator of transcription 3 pathway and
      triggering autophagic cell death. It is not known whether ERS mediates the cancer
      cell death induced by cucurbitacin-I. Here, we investigated the role of ERS in
      cucurbitacin-I-treated SKOV3 ovarian cancer cells and PANC-1 pancreatic cancer
      cells. We confirmed that cucurbitacin-I caused cell death and stirred excessive
      ERS levels by activating inositol requiring enzyme 1alpha (IRE1alpha) and protein
      kinase R-like endoplasmic reticulum kinase (PERK), as well as PERK downstream
      factors, including IRE1alpha and C/EBP homologous protein, but not activating
      transcription factor 6 (ATF6alpha) pathway, which was in parallel with the
      increased Bax and caspase-12-dependent ERS-associated apoptosis, autophagy and
      autophagy flux levels and caspase-independent nonapoptotic cell death.
      Furthermore, 4-phenylbutyrate, an ERS inhibitor, suppressed cucurbitacin-I
      induced apoptosis, autophagy, autophagy flux, and autophagic cell death.
      Simultaneously, there are positive correlations among ERS and cucurbitacin-I
      induced reactive oxygen species and Ca 2+. Our results suggested that
      cucurbitacin-I-induced cancer cell death through the excessive ERS and CHOP-Bax
      and caspase-12-dependent ERS-associated apoptosis, as well as ERS-dependent
      autophagy, autophagy flux, and caspase-independent nonapoptotic cell death. These
      novel signaling insights may be useful for developing new, effective anticancer
      strategies in oncotherapy.

PMID- 30277612
TI  - Astragaloside suppresses tumor necrosis factor receptor-associated factor 5
      signaling pathway and alleviates neurodegenerative changes in retinal pigment
      epithelial cells induced by isoflurane.
AB  - Epidemiological studies showed that isoflurane, a general anesthetic widely used
      in surgery including those for the children, is associated with impairment of
      neurodevelopment and neurodegenerative diseases, such as Alzheimer's disease (AD)
      and age-related macular degeneration (AMD), which are related to the accumulation
      of reactive oxygen species (ROS). Astragaloside (AS) is an antioxidant derivative
      from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge. In
      this study, we used retinal pigment epithelial cells, which share plenty of
      features with neurodegenerative diseases such as AD and AMD to investigate the
      effect of AS. Cell cycle re-entry and proapoptosis were seen in retinal pigment
      epithelium (RPE) cells treated with isoflurane, which was alleviated by
      pretreatment of AS. Further, tumor necrosis factor receptor-associated factor 5
      (TRAF5) and downstream nuclear factor-kappaB (NF-kappaB) were investigated to
      elucidate the molecular mechanism underlying protective effect of AS. RPE cells
      exposed to isoflurane expressed higher TRAF5 and NF-kappaB than those pretreated
      with AS, suggesting a critical role of TRAF5 therein. In Morris water maze (MWM)
      assay, Sprague-Dawley rats pretreated with AS and then exposed to isoflurane
      spent less time in swimming to the platform, and their TRAF5 expression was
      significantly lower than those received anesthesia alone. Further studies on the
      consequence of forced downregulation or upregulation are warranted that may
      employ cutting-edge technologies such as optogenetics to overcome the
      difficulties in manipulating expression of TRAF5. Although the link between TRAF5
      and neurodegeneration requires more in-depth investigations, our study provide a
      novel hint on the pathological mechanism of isoflurane and suggest a potential
      target for eliminating persistent side effect of anesthesia.

PMID- 30277610
TI  - Systems Thinking as a Framework for Analyzing Commercial Determinants of Health.
AB  - : Policy Points: Worldwide, more than 70% of all deaths are attributable to
      noncommunicable diseases (NCDs), nearly half of which are premature and apply to
      individuals of working age. Although such deaths are largely preventable,
      effective solutions continue to elude the public health community. One reason is
      the considerable influence of the "commercial determinants of health": NCDs are
      the product of a system that includes powerful corporate actors, who are often
      involved in public health policymaking. This article shows how a complex systems
      perspective may be used to analyze the commercial determinants of NCDs, and it
      explains how this can help with (1) conceptualizing the problem of NCDs and (2)
      developing effective policy interventions. CONTEXT: The high burden of
      noncommunicable diseases (NCDs) is politically salient and eminently preventable.
      However, effective solutions largely continue to elude the public health
      community. Two pressing issues heighten this challenge: the first is the public
      health community's narrow approach to addressing NCDs, and the second is the
      involvement of corporate actors in policymaking. While NCDs are often
      conceptualized in terms of individual-level risk factors, we argue that they
      should be reframed as products of a complex system. This article explores the
      value of a systems approach to understanding NCDs as an emergent property of a
      complex system, with a focus on commercial actors. METHODS: Drawing on Donella
      Meadows's systems thinking framework, this article examines how a systems
      perspective may be used to analyze the commercial determinants of NCDs and,
      specifically, how unhealthy commodity industries influence public health policy.
      FINDINGS: Unhealthy commodity industries actively design and shape the NCD policy
      system, intervene at different levels of the system to gain agency over policy
      and politics, and legitimize their presence in public health policy decisions.
      CONCLUSIONS: It should be possible to apply the principles of systems thinking to
      other complex public health issues, not just NCDs. Such an approach should be
      tested and refined for other complex public health challenges.

PMID- 30277613
TI  - MiR-125b suppresses the carcinogenesis of osteosarcoma cells via the MAPK-STAT3
      pathway.
AB  - The microRNA (miRNA) miR-125b is abnormally expressed in many different types of
      tumors, including osteosarcoma (OS). How aberrantly expressed miR-125b
      participates in regulating the initiation and progression of OS is still poorly
      understood. In the current study, we found that in OS, miR-125b can suppress the
      expression of MAP kinase kinase 7 (MKK7), which can dephosphorylate and
      inactivate signal transducer and activator of transcription 3 (STAT3). We also
      identified an elevated expression level of MKK7 in OS and an association between
      MKK7 expression and poor prognosis. Further, miR-125b inhibited OS cell
      proliferation and invasion by targeting and downregulating MKK7 in vitro and
      suppressed tumor formation in vivo. Moreover, using Western blot analysis, we
      preliminarily proved that the activation (phosphorylation) of STAT3 was regulated
      by MKK7 at the epigenetic level. MKK7 was overexpressed in OS and associated with
      poor clinical results. The miR-125b-MAPK-STAT3 axis may be one of the mechanisms
      of OS oncogenesis and a potential target for the treatment of OS.

PMID- 30277615
TI  - Planar-Chiral Ferrocene-Based N-Heterocyclic Carbene Ligands.
AB  - In the last few decades, N-heterocyclic carbene (NHC) ligands, characterized by
      attractive features, have increased their presence in transition-metal catalysis.
      However, chiral NHC ligands still require further design enhancement to realize
      far more exciting synthetic applications. This review documents advances in
      chiral NHC ligands, focusing on planar-chiral ferrocene-based NHCs. As the basic
      shape of most classes of NHC rings is planar, it seems rational to employ a
      planar-chiral element in the design of chiral NHC ligands.

PMID- 30277616
TI  - Tissue protein and lipid alterations in response to metallic impaction.
AB  - Tissue response to metallic contact and injury remains poorly understood at the
      level of proteins and lipid changes. We used corneas as a model system (bovine,
      porcine [n = 300 each], and human corneas [n = 6]) to characterize proteomic and
      lipidomic reactions to metallic exposure (impaction with iron). We also made a
      limited investigation into protein extractability and profile changes due to
      copper, and lead exposure as well. We identified selected proteins after trypsin
      digestion using an LCQ Deca XP and lipids using a TSQ Quantum Access Max mass
      spectrometer, respectively. Our findings indicate that iron impaction to corneal
      tissue results in cleavage of 1-phosphatidylinositol-4,5-bisphosphate
      phosphodiesterase beta-2 variant (PLCB2; 134 kDa) into a 36 kDa species and
      presence of the epithelial layer is necessary for this cleavage. Penetration of
      the cornea with other metals (copper and lead) resulted in lower protein
      extractability from corneal tissue compared with controls but not distinct
      changes in PLCB2. The changes in protein profiles were unique to the type of
      metal used for impaction. The depth of injury negatively affected protein
      extractability and profile compared with controls. These changes were also
      dependent on several other factors in a complex manner. Iron impaction of corneal
      tissue for 24 hours results in cleavage of PLCB2 commensurate with significant
      changes in phosphatidylinositols but not phosphatidylcholines or other
      phospholipids.

PMID- 30277618
TI  - An update and expansion on the role of the Violence Risk Appraisal Guide and
      Historical Clinical Risk Management-20 in United States case law.
AB  - An individual's risk for future violent behavior may be considered in various
      legal contexts, including civil commitment, criminal sentencing, or suitability
      for parole. Among the assessment tools forensic evaluators use to assess violence
      risk are the Violence Risk Appraisal Guide (VRAG; Quinsey, Harris, Rice, &
      Cormier, ) and the Historical Clinical Risk Managment-20 (HCR-20)/Historical
      Clinical Risk Management-20, Version 3 (HCR-20V3 ) (Webster, Douglas, Eaves, &
      Hart, and Douglas, Hart, Webster, & Belfrage, , respectively). Previous surveys
      and case law research suggest that these measures are widely used and perceived
      to be useful in aiding forensic clinicians. This study provides an update to
      Vitacco, Erickson, Kurus, and Apple () and examines the use of the HCR-20 and
      VRAG in United States case law. A LexisNexis review revealed 134 cases decided
      between 1 January 2010 and 21 December 2016 that included the HCR-20, VRAG, or
      both. Results revealed that these measures are typically introduced by the
      prosecution to inform opinions regarding general violence risk. In addition,
      consistent with previous research, these data suggest the introduction of the HCR
      20 and VRAG is rarely challenged and, when challenged, these challenges are
      rarely successful. However, data suggest that courts and parole boards may focus
      on specific risk factors (e.g., lack of insight) at the expense of other, more
      objective factors. Finally, we offer suggestions for clinicians who have
      transitioned to the newest version of the HCR-20.

PMID- 30277614
TI  - Genome-wide interaction studies identify sex-specific risk alleles for
      nonsyndromic orofacial clefts.
AB  - Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common
      craniofacial birth defect in humans and is notable for its apparent sexual
      dimorphism where approximately twice as many males are affected as females. The
      sources of this disparity are largely unknown, but interactions between genetic
      and sex effects are likely contributors. We examined gene-by-sex (G * S)
      interactions in a worldwide sample of 2,142 NSCL/P cases and 1,700 controls
      recruited from 13 countries. First, we performed genome-wide joint tests of the
      genetic (G) and G * S effects genome-wide using logistic regression assuming an
      additive genetic model and adjusting for 18 principal components of ancestry. We
      further interrogated loci with suggestive results from the joint test ( p < 1.00
      * 10 -5 ) by examining the G * S effects from the same model. Out of the 133 loci
      with suggestive results ( p < 1.00 * 10 -5 ) for the joint test, we observed one
      genome-wide significant G * S effect in the 10q21 locus (rs72804706; p = 6.69 *
      10 -9 ; OR = 2.62 CI [1.89, 3.62]) and 16 suggestive G * S effects. At the
      intergenic 10q21 locus, the risk of NSCL/P is estimated to increase with
      additional copies of the minor allele for females, but the opposite effect for
      males. Our observation that the impact of genetic variants on NSCL/P risk differs
      for males and females may further our understanding of the genetic architecture
      of NSCL/P and the sex differences underlying clefts and other birth defects.

PMID- 30277617
TI  - Engineering Anisotropic Muscle Tissue using Acoustic Cell Patterning.
AB  - Tissue engineering has offered unique opportunities for disease modeling and
      regenerative medicine; however, the success of these strategies is dependent on
      faithful reproduction of native cellular organization. Here, it is reported that
      ultrasound standing waves can be used to organize myoblast populations in
      material systems for the engineering of aligned muscle tissue constructs.
      Patterned muscle engineered using type I collagen hydrogels exhibits significant
      anisotropy in tensile strength, and under mechanical constraint, produced
      microscale alignment on a cell and fiber level. Moreover, acoustic patterning of
      myoblasts in gelatin methacryloyl hydrogels significantly enhances
      myofibrillogenesis and promotes the formation of muscle fibers containing aligned
      bundles of myotubes, with a width of 120-150 um and a spacing of 180-220 um. The
      ability to remotely pattern fibers of aligned myotubes without any material cues
      or complex fabrication procedures represents a significant advance in the field
      of muscle tissue engineering. In general, these results are the first instance of
      engineered cell fibers formed from the differentiation of acoustically patterned
      cells. It is anticipated that this versatile methodology can be applied to many
      complex tissue morphologies, with broader relevance for spatially organized cell
      cultures, organoid development, and bioelectronics.

PMID- 30277619
TI  - Multivalent Fucosides with Nanomolar Affinity for the Aspergillus fumigatus
      Lectin FleA Prevent Spore Adhesion to Pneumocytes.
AB  - FleA (or AFL), a fucose lectin, was recently identified in the opportunistic mold
      Aspergillus fumigatus, which causes fatal lung infections in immunocompromised
      patients. We designed di-, hexa- and octavalent fucosides with various spacer arm
      lengths to block the hexameric FleA through chelation. Microcalorimetry
      measurements showed that the ethylene glycol (EG) spacer arm length has a strong
      influence on the binding affinity of the divalent fucosides. The relationship
      between the EG length and chelate binding efficiency to FleA was explored
      according to polymer theory. Hexa- and octavalent compounds based on cyclodextrin
      and octameric silsesquioxane scaffolds were nanomolar FleA inhibitors, surpassing
      their monovalent fucose analogue by more than three orders of magnitude.
      Importantly, some of the fucosides were highly efficient in preventing fungal
      spore adhesion to bronchoepithelial cells, with half maximal inhibitory
      concentration values in the micromolar range. We propose that the synergistic
      antiadhesive effect observed can be ascribed to chelate binding to FleA and to
      the formation of conidium aggregates, as observed by optical microscopy. These
      fucosides are promising tools that can be used to better understand the role of
      FleA in conidia pathogenicity and host defenses against invasive aspergillosis.

PMID- 30277620
TI  - Tuning the photophysical properties of symmetric squarylium dyes: investigation
      on the halogen modulation effects.
AB  - A series of symmetric squarylium dyes (SQDPA-X) with different halogen (X = F,
      Cl, Br, I) substituents have been developed. The photophysical properties could
      be facilely tuned by the halogen modulation effects. The strategy of
      incorporating different halogen substitutions into AIE active luminogens enables
      a facile approach for exploring new intriguing organic fluorescent dyes.

PMID- 30277621
TI  - Syncytial isopotentiality: A system-wide electrical feature of astrocytic
      networks in the brain.
AB  - Syncytial isopotentiality, resulting from a strong electrical coupling, emerges
      as a physiological mechanism that coordinates individual astrocytes to function
      as a highly efficient system in brain homeostasis. However, whether syncytial
      isopotentiality occurs selectively to certain brain regions or is universal to
      astrocytic networks remains unknown. Here, we have explored the correlation of
      syncytial isopotentiality with different astrocyte subtypes in various brain
      regions. Using a nonphysiological K+-free/Na+ electrode solution to depolarize a
      recorded astrocyte in situ, the existence of syncytial isopotentiality can be
      revealed: the recorded astrocyte's membrane potential remains at a quasi
      physiological level due to strong electrical coupling with neighboring
      astrocytes. Syncytial isopotentiality appears in Layer I of the motor, sensory,
      and visual cortical regions, where astrocytes are organized with comparable cell
      densities, interastrocytic distances, and the quantity of directly coupled
      neighbors. Second, though astrocytes vary in their cytoarchitecture in
      association with neuronal circuits from Layers I-VI, the established syncytial
      isopotentiality remains comparable among different layers in the visual cortex.
      Third, neurons and astrocytes are uniquely organized as barrels in Layer IV
      somatosensory cortex; interestingly, astrocytes both inside and outside of the
      barrels do electrically communicate with each other and also share syncytial
      isopotentiality. Fourth, syncytial isopotentiality appears in radial-shaped
      Bergmann glia and velate astrocytes in the cerebellar cortex. Fifth, although
      fibrous astrocytes in white matter exhibit a distinct morphology, their network
      syncytial isopotentiality is comparable with protoplasmic astrocytes. Altogether,
      syncytial isopotentiality appears as a system-wide electrical feature of
      astrocytic networks in the brain.

PMID- 30277622
TI  - The role of the arcuate and middle longitudinal fasciculi in speech perception in
      noise in adulthood.
AB  - In this article, we used High Angular Resolution Diffusion Imaging (HARDI) with
      advanced anatomically constrained particle filtering tractography to investigate
      the role of the arcuate fasciculus (AF) and the middle longitudinal fasciculus
      (MdLF) in speech perception in noise in younger and older adults. Fourteen young
      and 15 elderly adults completed a syllable discrimination task in the presence of
      broadband masking noise. Mediation analyses revealed few effects of age on white
      matter (WM) in these fascicles but broad effects of WM on speech perception,
      independently of age, especially in terms of sensitivity and criterion (response
      bias), after controlling for individual differences in hearing sensitivity and
      head size. Indirect (mediated) effects of age on speech perception through WM
      microstructure were also found, after controlling for individual differences in
      hearing sensitivity and head size, with AF microstructure related to sensitivity,
      response bias and phonological priming, and MdLF microstructure more strongly
      related to response bias. These findings suggest that pathways of the perisylvian
      region contribute to speech processing abilities, with relatively distinct
      contributions for the AF (sensitivity) and MdLF (response bias), indicative of a
      complex contribution of both phonological and cognitive processes to age-related
      speech perception decline. These results provide new and important insights into
      the roles of these pathways as well as the factors that may contribute to elderly
      speech perception deficits. They also highlight the need for a greater focus to
      be placed on studying the role of WM microstructure to understand cognitive
      aging.

PMID- 30277623
TI  - Direct and cascading effects of landscape structure on tropical forest and non
      forest frugivorous birds.
AB  - Global biodiversity is increasingly threatened by land-use change, but the direct
      and indirect drivers of species diversity in human-modified tropical landscapes
      are poorly known. Forest-dependent species are expected to be particularly
      sensitive to changes in landscape composition (e.g., forest loss) and
      configuration (e.g., increase of forest edges), both directly and indirectly
      through cascading landscape effects on local patterns of forest structure and
      resource availability. In contrast, non-forest-dependent species are probably
      more strongly related to landscape changes than to local forest patterns, as
      these species are able to use resources not only from the forest, but also from
      other landscape elements over larger spatial scales. We tested these hypotheses
      using structural equation modeling. In particular, we sampled 20 landscapes (115
      ha each) from the Brazilian Atlantic rainforest to assess the effect of landscape
      scale forest cover and amount of forest edges on the diversity of frugivorous
      birds, both directly and indirectly through the effect that these landscape
      variables may have on vegetation complexity and fruit biomass. We separately
      assessed the response of forest-dependent and non-forest-dependent frugivores to
      infer potential mechanisms underlying bird assemblages in fragmented landscapes.
      The diversity of forest-dependent birds mainly decreased with the simplification
      of vegetation complexity in more deforested landscapes, but increased with
      increasing fruit biomass in more forested landscapes (indirect effects). Both
      patterns were significant, thus supporting a strong bottom-up control, i.e.,
      local habitat simplification and resource scarcity in highly deforested
      landscapes limits the maintenance of forest-dependent birds. Conversely, but as
      expected, non-forest-dependent birds were more strongly and directly related to
      landscape-scale patterns. In particular, landscapes with higher forest edge
      amount showed higher bird species diversity, probably because the increasing
      length of ecotones and interspersion/juxtaposition of different habitat types in
      landscapes with more forest edges can increase resource availability and foraging
      efficiency of non-forest-dependent birds. As the seed dispersal services offered
      by forest-dependent species cannot be ecologically compensated for by the
      proliferation of non-forest-dependent species, preventing forest loss is
      imperative to maintain forest-dependent birds and forest regeneration in this
      vanishing biodiversity hotspot.

PMID- 30277624
TI  - Adaptation of brain functional stream architecture in athletes with fast demands
      of sensorimotor integration.
AB  - Training-induced neuroplasticity has been described in athletes' population.
      However, it remains largely unknown how regular training and sports proficiency
      modifies neuronal circuits in the human brain. In this study, we used voxel-based
      morphometry and stepwise functional connectivity (SFC) analyses to uncover
      connectivity changes in the functional stream architecture in student-athletes at
      early stages of sensorimotor skill training. Thirty-two second-year student
      athletes whose major was little-ball sports and thirty-four nonathlete controls
      were recruited for the study. We found that athletes showed greater gray matter
      volume in the right sensorimotor area, the limbic lobe, and the anterior lobe of
      the cerebellum. Furthermore, SFC analysis demonstrated that athletes displayed
      significantly smaller optimal connectivity distance from those seed regions to
      the dorsal attention network (DAN) and larger optimal connectivity distance to
      the default mode network (DMN) compared to controls. The Attention Network Test
      showed that the reaction time of the orienting attention subnetwork was
      positively correlated with SFC between the seeds and the DAN, while negatively
      correlated with SFC between the seeds and the DMN. Our findings suggest that
      neuroplastic adaptations on functional connectivity streams after motor skill
      training may enable novel information flow from specific areas of the cortex
      toward distributed networks such as the DAN and the DMN. This could potentially
      regulate the focus of external and internal attention synchronously in athletes,
      and consequently accelerate the reaction time of orienting attention in athletes.

PMID- 30277625
TI  - Course and stability of cognitive and metacognitive beliefs in depression.
AB  - Maladaptive cognitive beliefs as measured by the Dysfunctional Attitudes Scale
      (DAS) increase vulnerability to depression. Maladaptive metacognitive beliefs as
      measured by the Metacognitive Questionnaire-30 (MCQ-30) are also thought to
      contribute to depression. However, the long-term stability of metacognitive
      beliefs in depression has not yet been investigated. It is unclear whether
      metacognitive beliefs can add explanatory power to depression above and beyond
      maladaptive cognitive beliefs. The aim of the present study was to investigate
      the role and stability of cognitive and metacognitive maladaptive beliefs in
      depression. Eighty-four patients with depression were assessed with the DAS,
      three subscales of the MCQ-30 (positive metacognitive beliefs about worry and
      rumination [PB]; negative metacognitive beliefs about the uncontrollability of
      rumination [NB]; metacognitive beliefs concerning the need to control one's
      thoughts [NFC]), the Hamilton Depression Rating Scale, and the Beck Depression
      Inventory at baseline and were reassessed 3.5 years later. Analyses using a
      longitudinal latent growth model showed that change on the DAS and baseline
      scores and change on the MCQ-30 (NB and NFC) significantly predicted change in
      self-rated depressive symptoms over 3.5 years. However, the DAS explained more
      additional variance than the integration of the MCQ-30 subscales. Subscales of
      the MCQ-30 were more stable than the DAS. Although cognitive and metacognitive
      maladaptive beliefs were both predictors of depression, the DAS was a better
      predictor than the MCQ-30 subscales. Nevertheless, because maladaptive
      metacognitive beliefs were more stable than maladaptive cognitive beliefs, they
      should be considered an important underlying vulnerability factor for depression.

PMID- 30277626
TI  - Helicobacter: Inflammation, immunology, and vaccines.
AB  - Helicobacter pylori infection induces a chronic gastric inflammation which can
      lead to gastric ulcers and cancer. The mucosal immune response to H. pylori is
      first initiated by the activation of gastric epithelial cells that respond to
      numerous bacterial factors, such as the cytotoxin-associated gene A or the
      lipopolysaccharide intermediate heptose-1,7-bisphosphate. The response of these
      cells is orchestrated by different receptors including the intracellular
      nucleotide-binding oligomerization domain-containing protein 1 or the
      extracellular epidermal growth factor receptor. This nonspecific response leads
      to recruitment and activation of various myeloid (macrophages and dendritic
      cells) and T cells (T helper-17 and mucosal-associated invariant T cells), which
      magnify and maintain inflammation. In this review, we summarize the major
      advances made in the past year regarding the induction, the regulation, and the
      role of the innate and adaptive immune responses to H. pylori infection. We also
      recapitulate efforts that have been made to develop efficient vaccine strategies.

PMID- 30277627
TI  - Randomized trial of the efficacy of intravaginal ulinastatin administration for
      the prevention of preterm birth in women with a singleton pregnancy and both
      cervical shortening and inflammation of lower genital tract.
AB  - AIM: To assess the preventive effect on preterm birth of intravaginal ulinastatin
      (urinary trypsin inhibitor; UTI) administration during the mid-trimester in women
      with singleton pregnancy and both cervical shortening and lower genital
      infections. METHODS: Pregnant women with a short cervical length < 25 mm between
      16 and 26 weeks of gestation and who had been diagnosed with a lower genital
      infection were randomly assigned for intravaginal UTI administration or placebo.
      All of the women were screened for infection or inflammation of the lower genital
      tract, and women with negative results were excluded. RESULTS: Of the 92 patients
      with a short cervical length who were assessed for eligibility for this study, 86
      singleton patients were enrolled. All patients were randomized to one of two
      treatment groups: patients administered UTI (n = 35) and placebo (n = 35). There
      were no differences between the two groups in the incidence of preterm delivery
      before 28, 30, 32, 34 and 37 weeks of gestation and in perinatal outcomes.
      CONCLUSION: For women diagnosed with a short cervical length < 25 mm) between 16
      and 26 weeks of gestation and lower genital infection, who were at risk of
      preterm birth, administration of transvaginal UTI with vaginal irrigation showed
      no apparent benefit. Future research on the efficacy of UTI should evaluate
      modified modes of UTI application.

PMID- 30277628
TI  - Volumetric Apparent Diffusion Coefficient Histogram Analysis in Differentiating
      Intrahepatic Mass-Forming Cholangiocarcinoma From Hepatocellular Carcinoma.
AB  - BACKGROUND: Accurate differentiation between intrahepatic mass-forming
      cholangiocarcinoma (IMCC) and hepatocellular carcinoma (HCC) is needed because
      treatment and prognosis differ significantly. PURPOSE: To explore whether
      volumetric apparent diffusion coefficient (ADC) histogram analysis can provide
      additional value to dynamic enhanced MRI in differentiating IMCC from HCC. STUDY
      TYPE: Retrospective. POPULATION: In all, 131 patients with pathologically proven
      IMCC (n = 33) or HCC (n = 98). FIELD STRENGTH/SEQUENCE: 3.0T MRI/conventional T1
      weighted imaging (T1WI), T2WI, and diffusion-weighted imaging (DWI) with b value
      of 800 sec/mm2, dynamic enhanced MRI with gadobenate dimeglumine. ASSESSMENT:
      Dynamic enhanced MR images were analyzed by two independent reviewers using a
      five-point scale to determine the diagnosis. Volumetric ADC assessments were
      performed independently by two radiologists to obtain different histogram
      parameters for each lesion. Quantitative histogram parameters were compared
      between the IMCC group and HCC group. Diagnostic performance of dynamic enhanced
      MRI, volumetric ADC histogram analysis, and the combination of both were
      analyzed. STATISTICAL TESTS: Intraclass correlation coefficient (ICC) analysis,
      independent Student's t-test, or Mann-Whitney U-test, receiver operator
      characteristic (ROC) curves analysis, and McNemar test. RESULTS: The sensitivity
      and specificity for dynamic enhanced MRI to differentiate IMCC from HCC were
      82.1% and 82.6%, respectively. For all volumetric ADC histogram parameters, the
      75th percentile ADC (ADC75%) had the highest AUC (0.791) in differentiating IMCC
      from HCC, with sensitivity and specificity of 69.7% and 77.6%, respectively. When
      combining dynamic enhanced MRI with ADC75%, the sensitivity and specificity were
      82.1% and 91.9%, respectively. Compared to dynamic enhanced MRI alone, the
      specificity for combined dynamic enhanced MRI and ADC75% was significantly
      increased (P = 0.008). DATA CONCLUSION: Volumetric ADC histogram analysis
      provides additional value to dynamic enhanced MRI in differentiating IMCC from
      HCC. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING
      2018.

PMID- 30277629
TI  - Shifted balance of dorsal versus ventral striatal communication with frontal
      reward and regulatory regions in cannabis-dependent males.
AB  - The transition from voluntary to addictive behavior is characterized by a loss of
      regulatory control in favor of reward driven behavior. Animal models indicate
      that this process is neurally underpinned by a shift in ventral-dorsal striatal
      control of behavior; however, this shift has not been directly examined in
      humans. The present resting state functional magnetic resonance imaging (fMRI)
      study employed a two-step approach to: (a) precisely map striatal alterations
      using a novel, data-driven network classification strategy combining intrinsic
      connectivity contrast with multivoxel pattern analysis and, (b) to determine
      whether a ventral to dorsal striatal shift in connectivity with reward and
      regulatory control regions can be observed in abstinent (28 days) male cannabis
      dependent individuals (n = 24) relative to matched controls (n = 28). Network
      classification revealed that the groups can be reliably discriminated by global
      connectivity profiles of two striatal regions that mapped onto the ventral
      (nucleus accumbens) and dorsal striatum (caudate). Subsequent functional
      connectivity analysis demonstrated a relative shift between ventral and dorsal
      striatal communication with fronto-limbic regions that have been consistently
      involved in reward processing (rostral anterior cingulate cortex [ACC]) and
      executive/regulatory functions (dorsomedial prefrontal cortex [PFC]).
      Specifically, in the cannabis-dependent subjects, connectivity between the
      ventral striatum with the rostral ACC increased, whereas both striatal regions
      were uncoupled from the regulatory dorsomedial PFC. Together, these findings
      suggest a shift in the balance between dorsal and ventral striatal control in
      cannabis dependence. Similar changes have been observed in animal models and may
      promote the loss of control central to addictive behavior.

PMID- 30277630
TI  - The new neuroendocrinology-a perspective.

PMID- 30277631
TI  - Long-Chain Hyperbranched Polymers: Synthesis, Properties, and Applications.
AB  - By combining the virtues of conventional linear and hyperbranched polymers, long
      chain hyperbranched polymers (LCHBPs) have attracted great attention. Therefore,
      a comprehensive summary of the research progress of LCHBPs is presented, with a
      particular focus on their synthetic strategies, unique properties, and potential
      applications. The synthetic methodologies are rationalized into four main classes
      according to their construction process or mechanism, namely ABx (x >= 2), A2 +
      Bx (x >= 3), AB + ABx (x >= 2), and self-condensing vinyl polymerization. Some of
      their rheological properties, self-assembly behavior, and stimuli-response
      features are then discussed. Finally, the emergent applications including
      biomedicine, electrical conductivity, chemical sensing, and catalyst carrier, are
      outlined. It is anticipated that this review will stimulate more inspiration for
      advancing the development of this novel kind of LCHBP.

PMID- 30277632
TI  - Quality of online information about phase I clinical cancer trials in Sweden,
      Denmark and Norway.
AB  - Patients increasingly search for online information about clinical trials. Little
      is known about the quality and readability of the information in these databases.
      Therefore, the aim of this study was to assess the quality and readability of
      online information available to the public on phase I clinical cancer trials in
      Sweden, Denmark and Norway. A qualitative content analysis was made of 19 online
      trial descriptions from three public websites in Sweden, Denmark and Norway, and
      the readability of the documents was tested. Both the quality of the content and
      the readability scores were best for the Danish information. The Swedish texts
      were very short and were the least readable. Overall, the quality of the
      information was highly variable and nearly all the documents were misleading in
      part. Furthermore, the descriptions provided almost no information about possible
      adverse effects or disadvantages of study participation. This study highlights a
      communication problem and proposes new ways of presenting studies that are less
      suggestive of positive outcomes, arguing that we should be more careful to
      include information about adverse effects, and that the use of simple measures
      like readability testing can be useful as an indicator of text quality.

PMID- 30277633
TI  - 12/10-Helix in Mixed beta-Peptides Alternating Bicyclic and Acyclic beta-Amino
      Acids: Probing the Relationship between Bicyclic Side Chain and Helix Stability.
AB  - 12/10-Helices constitute suitable templates that can be used to design original
      structures. Nevertheless, they often suffer from a weak stability in polar
      solvents because they exhibit a mixed hydrogen-bond network resulting in a small
      macrodipole. In this work, stable and functionalizable 12/10-helices were
      developed by alternating a highly constrained beta2, 3, 3 -trisubstituted
      bicyclic amino acid (S)-1-aminobicyclo[2.2.2]octane-2-carboxylic acid ((S)-ABOC)
      and an acyclic substituted beta-homologated proteinogenic amino acid (l-beta3 
      hAA). Based on NMR spectroscopic analysis, it was shown that such mixed beta
      peptides display well-defined right-handed 12/10-helices in polar, apolar, and
      chaotropic solvents; that are, CD3 OH, CDCl3 , and [D6 ]DMSO, respectively. The
      stability of the hydrogen bonds forming the C10 and C12 pseudocycles as well as
      the benefit provided by the use of the constrained bicyclic ABOC versus typical
      acyclic beta-amino acids sequences when designing 12/10-helix were investigated
      using NH/ND NMR exchange experiments and DFT calculations in various solvents.
      These studies showed that the beta3 -hAA/(S)-ABOC helix displayed a more stable
      hydrogen-bond network through specific stabilization of the C10 pseudocycles
      involving the bridgehead NH of the ABOC bicyclic scaffold.

PMID- 30277634
TI  - Reversible and Tunable Photoswitching of Protein Function through Genetic
      Encoding of Azobenzene Amino Acids in Mammalian Cells.
AB  - The genetic encoding of three different azobenzene phenylalanines with different
      photochemical properties was achieved in human cells by using an engineered
      pyrrolysyl tRNA/tRNA synthetase pair. In order to demonstrate reversible light
      control of protein function, azobenzenes were site-specifically introduced into
      firefly luciferase. Computational strategies were applied to guide the selection
      of potential photoswitchable sites that lead to a reversibly controlled
      luciferase enzyme. In addition, the new azobenzene analogues provide enhanced
      thermal stability, high photoconversion, and responsiveness to visible light.
      These small-molecule photoswitches can reversibly photocontrol protein function
      with excellent spatiotemporal resolution, and preferred sites for incorporation
      can be computationally determined, thus providing a new tool for investigating
      biological processes.

PMID- 30277635
TI  - Alcohol-induced cognitive deficits are associated with decreased circulating
      levels of the neurotrophin BDNF in humans and rats.
AB  - Chronic alcohol consumption is associated with neurocognitive and memory
      deficits, dramatically affecting plasticity and connectivity, with maximal
      expression as dementia. Neurotrophic factors may contribute to alcohol-related
      cognitive decline. For further investigation, a cross-sectional study was
      performed to evaluate the association of cognitive impairment, by using frontal
      assessment battery, and memory loss, using memory failures everyday, with the
      circulating levels of the neurotrophin brain-derived neurotrophic factor (BDNF)
      and neurotrophin 3 (NT-3) in abstinent subjects with alcohol use disorders (AUDs,
      N = 58, average of 17.9 years of problematic use and 4.3 months of abstinence)
      compared with healthy control subjects (N = 22). This association was also
      explored in a pre-clinical model of adolescent rats chronically exposed to
      alcohol up to adulthood (~77 days old) in a three-bottle free-choice (5-10-20
      percent), repeated abstinence and relapse paradigm. AUD subjects had low
      educational level and cognitive impairment associated with teenage consumption
      and lower circulating levels of BDNF and NT-3. Only BDNF concentration showed a
      positive correlation with frontal assessment battery in AUD patients. In the
      ethanol-exposed rats, the plasma levels of BDNF and NT-3 were also decreased, and
      a negative correlation between hippocampal Bdnf mRNA levels and recognition
      memory was found. The ethanol-exposed rat hippocampus showed a decrease in the
      mRNA levels of neurotrophic (Bdnf and Ntf-3) and neurogenic (Mki67, Sox2, Dcx,
      Ncam1 and Calb1) factors, associated to a deactivation of the neurogenic
      regulator mitogen-activated protein kinase extracellular signal-regulated kinase.
      Results suggest a relevant role of BDNF/extracellular signal-regulated kinase 2
      signaling in alcohol-induced cognitive impairment and suggest that early alcohol
      exposure-derived effects on cognition are associated with neurotrophin signaling
      deficits.

PMID- 30277636
TI  - Gastric cancer: Basic aspects.
AB  - Despite major breakthroughs in the field of personalized medicine, gastric cancer
      (GC) remains a clinically challenging disease, characterized by scarce effective
      treatment options and the lack of reliable molecular tools for the prediction of
      patient outcome and response to therapy. The pronounced molecular heterogeneity
      that dictates the phenotypical aggressiveness of gastric neoplasms severely
      limits the antitumor efficacy of targeted agents brought to clinical trials, and
      constitutes a favorable setting for the emergence of refractory tumors exhibiting
      multidrug resistance. We will review the most recent advances in our
      understanding of GC biology, which are underlying the development and clinical
      testing of novel targeted therapeutic agents. We will also emphasize how their
      efficacy and acquired resistance relate to the aberrant molecular signatures that
      drive gastric malignancy.

PMID- 30277637
TI  - A Clade II-D Fungal Chimeric Diterpene Synthase from Colletotrichum
      gloeosporioides Produces Dolasta-1(15),8-diene.
AB  - Based on a terpenoid overproduction platform in yeast for genome mining, a
      chimeric diterpene synthase from the endophytic fungus Colletotrichum
      gloeosporioides ES026 was characterized as the (5R,12R,14S)-dolasta-1(15),8-diene
      synthase. The absolute configuration was independently verified through the use
      of enantioselectively deuterated terpene precursors, which unequivocally
      established the predicted C1-III-IV cyclization mode for this first characterized
      clade II-D enzyme. Extensive isotopic labeling experiments and isolation of the
      intermediate (1R)-delta-araneosene supported the proposed cyclization mechanism.

PMID- 30277638
TI  - Metal phosphorous trichalcogenides (MPCh3): from synthesis to contemporary energy
      challenges.
AB  - Layered two-dimensional (2D) materials have been establish as the most
      significant topic in materials science for the current decade, arising to their
      unique physical and chemical properties. From mono-element (graphene,
      phosphorene, etc.) to the more commonly found containing two (metal
      dichalcogenides) or even further elements. A distinctive class of 2D layered
      materials are the metal phosphorous trichalcogenides (MPCh3, Ch=S, Se), first
      synthetized in the late 1800s. Having an unusual intercalation behavior, MPCh3
      were intensively studied in the 1970s for their magnetism and as secondary
      electrodes in lithium batteries but fell under the radar, until very recently
      being included in the loop of 2D nanomaterials. Considering their synthesis and
      most significant properties, the present uprising of reports related to water
      splitting catalysis and energy storage in discussed in detail. This review is
      intended as comprehensive baseline for the anticipated new wave of researchers
      who aim to explore these 2D layered materials advancements in their
      electrochemical energy applications.

PMID- 30277640
TI  - Development and evaluation of a food frequency questionnaire to assess nutrient
      intakes of adult women in New Zealand.
AB  - AIM: In New Zealand, there are few adequate food frequency questionnaires for
      assessing dietary intake. This study aimed to develop and assess the relative
      validity of a multi-nutrient, culturally appropriate, semi-quantitative food
      frequency questionnaire for use in young adult New Zealand women (the New Zealand
      Women's Food Frequency Questionnaire (NZWFFQ)). METHODS: Women (n = 110) aged 16
      45 years of Maori, Pacific or European ethnicity completed a NZWFFQ assessing
      dietary intake over the previous month, and a 4-day weighed food record. Relative
      validity was evaluated by comparing nutrient intakes from the NZWFFQ with the
      food record using Spearman's rank correlation coefficients, cross-classification,
      the weighted kappa statistic and Bland-Altman analysis. RESULTS: Nutrient intake
      was higher from the NZWFFQ compared with the food record for all nutrients
      (range: 1%-64% difference) except alcohol (-16% difference). Energy-adjusted
      correlations ranged from 0.23 to 0.67 (average 0.48). Correct classification into
      same and adjacent quartiles was over 70% for all nutrients except folate and
      vitamin D. Gross misclassification into opposite quartiles ranged from 1%
      (monounsaturated fat, magnesium, calcium) to 10% (iron). The weighted kappa
      showed poor agreement for vitamin D and folate, fair agreement for most
      nutrients, and moderate agreement for fibre, vitamin E, magnesium, calcium and
      phosphorus. CONCLUSIONS: The NZWFFQ overestimated intake of nearly all nutrients.
      While not suitable for assessing absolute intake, the NZWFFQ is suitable for
      ranking individuals based on nutrient intake demonstrating reasonable relative
      validity for this purpose.

PMID- 30277639
TI  - Outcomes in intermediate-risk pediatric lymphocyte-predominant Hodgkin lymphoma:
      A report from the Children's Oncology Group.
AB  - PURPOSE: Optimal management of patients with intermediate-risk lymphocyte
      predominant Hodgkin lymphoma (LPHL) is unclear due to their small numbers in most
      clinical trials. Children's Oncology Group AHOD0031, a randomized phase III trial
      of pediatric patients with intermediate-risk Hodgkin lymphoma (HL), included
      patients with LPHL. We report the outcomes of these patients and present
      directions for future therapeutic strategies. PROCEDURE: Patients received two
      cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and
      cyclophosphamide (ABVE-PC) followed by response evaluation. Slow early responders
      were randomized to two additional ABVE-PC cycles +/- two dexamethasone,
      etoposide, cisplatin, and cytarabine cycles and all received involved field
      radiotherapy (IFRT). Rapid early responders (RERs) received two additional ABVE
      PC cycles. RERs with complete response (CR) were randomized to IFRT or no further
      therapy. RERs without CR received IFRT. RESULTS: Ninety-six (5.6%) of 1711
      patients on AHOD0031 had LPHL. Patients with LPHL were more likely to achieve RER
      (93.6% vs. 81.0%; P = 0.002) and CR (74.2% vs. 49.3%; P = 0.000005) following
      chemotherapy compared with patients with classical HL. Five-year event-free
      survival (EFS) was superior in patients with LPHL (92.2%) versus classical HL
      (83.5%) (P = 0.04), without difference in overall survival (OS). Among RERs with
      CR following chemotherapy (n = 33), there was no difference in EFS or OS between
      those randomized to receive or not receive IFRT. CONCLUSION: Children and
      adolescents with intermediate-risk LPHL represent ideal candidates for response
      adapted therapy based on their favorable outcomes. The majority of patients
      treated with the ABVE-PC backbone achieve RER with CR status and can be treated
      successfully without IFRT.

PMID- 30277641
TI  - Coronary fractional flow reserve derived from intravascular ultrasound imaging:
      Validation of a new computational method of fusion between anatomy and
      physiology.
AB  - OBJECTIVES: To evaluate the diagnostic performance of a novel computational
      algorithm based on three-dimensional intravascular ultrasound (IVUS) imaging in
      estimating fractional flow reserve (IVUSFR), compared to gold-standard invasive
      measurements (FFRINVAS). BACKGROUND: IVUS provides accurate anatomical evaluation
      of the lumen and vessel wall and has been validated as a useful tool to guide
      percutaneous coronary intervention. However, IVUS poorly represents the
      functional status (i.e., flow-related information) of the imaged vessel. METHODS:
      Patients with known or suspected stable coronary disease scheduled for elective
      cardiac catheterization underwent FFRINVAS measurement and IVUS imaging in the
      same procedure to evaluate intermediate lesions. A processing methodology was
      applied on IVUS to generate a computational mesh condensing the geometric
      characteristics of the vessel. Computation of IVUSFR was obtained from patient
      level morphological definition of arterial districts and from territory-specific
      boundary conditions. FFRINVAS measurements were dichotomized at the 0.80
      threshold to define hemodynamically significant lesions. RESULTS: A total of 24
      patients with 34 vessels were analyzed. IVUSFR significantly correlated (r =
      0.79; P < 0.001) and showed good agreement with FFRINVAS, with a mean difference
      of -0.008 +/- 0.067 (P = 0.47). IVUSFR presented an overall accuracy,
      sensitivity, specificity, positive predictive value, and negative predictive
      value of 91%, 89%, 92%, 80%, and 96%, respectively, to detect significant
      stenosis. CONCLUSION: The computational processing of IVUSFR is a new method that
      allows the evaluation of the functional significance of coronary stenosis in an
      accurate way, enriching the anatomical information of grayscale IVUS.

PMID- 30277643
TI  - Borocyclopropanation of Styrenes Mediated by UV-light Under Continuous Flow
      Conditions.
AB  - Herein, we report a user-friendly and metal-free UV-A light mediated
      borocyclopropanation of styrenes using continuous flow technology. A broad range
      of styrene derivatives can be cyclopropanated in good yields within 1 h residence
      time to produce highly valuable cyclopropylboronate esters with modest to good
      diastereoselectivities. The reaction is also applicable to alpha-substituted
      styrenes. Mechanistic studies support a photoredox process during which xanthone,
      a well-known organic photosensitizer, can easily reach a photoexcited state that
      is available for both an oxidative and a reductive quenching.

PMID- 30277642
TI  - Hypertensive organ damage predicts future cognitive performance: A 9-year follow
      up study in patients with hypertension.
AB  - Hypertension is associated with cognitive deficits, probably caused by cerebral
      small vessel disease. The authors examined whether additional presence of cardiac
      and renal organ damages, and their combined presence, are associated with future
      cognitive performance. In 78 patients with essential hypertension (mean age 51.2
      +/- 12.0 years), brain damage was determined by MRI features, cardiac damage by
      left ventricular mass index (LVMI), and renal damage by estimated glomerular
      filtration rate (eGFR) and albuminuria. At 9-year follow-up, neuropsychological
      assessment was performed. LVMI was associated with future lower cognition (P =
      0.032), independent of age, sex, premorbid cognition, and brain damage, but eGFR
      and albuminuria were not. The presence of 2 or 3 types of organ damage compared
      to none was associated with future lower cognition. Increasing number of
      hypertensive organ damages, and cardiac damage independently of brain damage,
      might indicate a more severe hypertensive disease burden and could help to
      identify patients at risk of cognitive problems.

PMID- 30277644
TI  - Drug Design Concepts for LSD1-Selective Inhibitors.
AB  - Lysine-specific demethylase 1 (LSD1) is one of the flavin-dependent oxidases and
      is involved in many cellular processes by controlling the methylation of histone
      H3. Recently, it has been reported that LSD1 is associated with several diseases
      such as cancer, metabolic disorders, and psychiatric diseases. Thus, LSD1 is an
      attractive molecular target for the treatment of these diseases, and its
      inhibitors are predicted as therapeutic agents. Although a variety of LSD1
      inhibitors have been reported to date, many of them show insufficient activities
      and selectivity toward LSD1. Meanwhile, we identified several LSD1-selective
      inhibitors using target-guided synthesis strategies based on our original ideas.
      Our LSD1 inhibitors show not only potent LSD1-selective inhibitory activities,
      but also unique bioactivities both in vitro and in vivo. This account highlights
      our drug design concepts for and identification of LSD1-selective inhibitors.

PMID- 30277645
TI  - Microwave Flow Chemistry as a Methodology in Organic Syntheses, Enzymatic
      Reactions, and Nanoparticle Syntheses.
AB  - Several studies have used microwaves as a heat source for carrying out various
      types of reactions employing circulation reaction vessels. The microwave flow
      chemical synthesis methodology is most appropriate in the use of microwaves in
      chemical syntheses. It can attenuate the problem of microwave heating (non
      uniform heating and penetration depth) and maximize the benefits (rapid heating
      and first temperature adjustments). In this brief review, we examine and explain
      some of the relevant features of microwave heating with applicative examples of
      the usage of microwave flow chemistry equipment in carrying out organic
      syntheses, enzymatic reactions, and (not least) nanoparticle syntheses.

PMID- 30277646
TI  - The Catalytic Reduction of Carboxylic Acid Derivatives and CO2 by Metal
      Nanoparticles on Lewis-Acidic Supports.
AB  - The development of heterogeneous catalysts for green chemical synthesis is
      currently a growing area in catalysis and sustainable chemistry. Especially the
      use of renewable carbon resources such as carbon dioxide (CO2 ) and biomass
      derived compounds (e. g. carboxylic acids, esters, and amides) represent highly
      attractive research targets. As these substances reside in a high oxidation
      state, efficient reduction processes are required in order to convert these
      substrates into useful and value-added chemicals. Moreover, in the interest of
      mass production, these substrates should be reduced by molecular H2 and a
      heterogeneous catalyst. In this context, our group has developed advanced
      catalysts and established design guidelines for catalysts that promote the
      reductive transformations of carboxylic acid derivatives and CO2 . Our studies
      show that cooperative catalysis between Lewis-acidic sites on the catalyst
      support and supported metal nanoparticles are crucial for the success of these
      challenging hydrogenations. In this review, we summarize the results of our
      recent studies on the direct synthesis of value-added chemicals from CO2 and
      carboxylic acid derivatives using supported transition-metal catalysts, and we
      propose a design concept for heterogeneous catalysts that promote these
      processes.

PMID- 30277647
TI  - Recent Progress in Sublimable Cationic Iridium(III) Complexes for Organic Light
      Emitting Diodes.
AB  - Sublimable cationic iridium(III) complexes consisting of light-emitting
      coordinated iridium(III) cations and nonluminous negative counter-ions, show
      excellent photophysical properties, superior electrochemical behaviors and high
      thermal stabilities, therefore have emerged as a new library of phosphorescent
      materials for various organic optoelectronic devices. Here we summarize and
      highlight the recent progress in sublimable cationic iridium(III) complexes,
      regarding the material design strategies, synthetic routes, photoluminescent
      characteristics in both solutions and neat films, together with the current
      utilization in organic light-emitting diodes based on the emissive material
      layers fabricated by vacuum evaporation deposition. Finally, we present a brief
      outlook thereon, indicating the great promise and brilliant application prospect
      of sublimable cationic iridium(III) complexes in future flat-panel display and
      solid-state lighting technology.

PMID- 30277648
TI  - High-production dairy cattle exhibit different rumen and fecal bacterial
      community and rumen metabolite profile than low-production cattle.
AB  - Our aim was to simultaneously investigate the gut bacteria typical characteristic
      and conduct rumen metabolites profiling of high production dairy cows when
      compared to low-production dairy cows. The bacterial differences in rumen fluid
      and feces were identified by 16S rDNA gene sequencing. The metabolite differences
      were identified by metabolomics profiling with liquid chromatography mass
      spectrometry (LC-MS). The results indicated that the high-production dairy cows
      presented a lower rumen bacterial richness and species evenness when compared to
      low-production dairy cows. At the phylum level, the high-production cows
      increased the abundance of Proteobacteria and decreased the abundance of
      Bacteroidetes, SR1, Verrucomicrobia, Euryarchaeota, Planctomycetes,
      Synergistetes, and Chloroflexi significantly (p < 0.05). At the genus level, the
      rumen fluid of the high-production group was significantly enriched for
      Butyrivibrio, Lachnospira, and Dialister (p < 0.05). Meanwhile, rumen fluid of
      high-production group was depleted for Prevotella, Succiniclasticum, Ruminococcu,
      Coprococcus,YRC22, CF231, 02d06, Anaeroplasma, Selenomonas, and Ruminobacter
      significantly (p < 0.05). A total of 92 discriminant metabolites were identified
      between high-production cows and low-production cows. Compared to rumen fluid of
      low-production dairy cows, 10 differential metabolites were found up-regulated in
      rumen fluid of high-production dairy cows, including 6alpha-Fluoropregn-4-ene
      3,20-dione, 3-Octaprenyl-4-hydroxybenzoate, disopyramide, compound III(S), 1,2
      Dimyristyl-sn-glycerol, 7,10,13,16-Docosatetraenoic acid, ferrous lactate, 6
      Deoxyerythronolide B, vitamin D2, L-Olivosyl-oleandolide. The remaining
      differential metabolites were found down-regulated obviously in high-production
      cows. Metabolic pathway analyses indicated that most increased abundances of
      rumen fluid metabolites of high-yield cows were related to metabolic pathways
      involving biosynthesis of unsaturated fatty acids, steroid biosynthesis,
      ubiquinone and other terpenoid-quinone biosynthesis. Most down-regulated
      metabolic pathways were relevant to nucleotide metabolism, energy metabolism,
      lipid metabolism and biosynthesis of some antibiotics.

PMID- 30277649
TI  - cytometree: A binary tree algorithm for automatic gating in cytometry analysis.
AB  - Flow cytometry is a powerful technology that allows the high-throughput
      quantification of dozens of surface and intracellular proteins at the single-cell
      level. It has become the most widely used technology for immunophenotyping of
      cells over the past three decades. Due to the increasing complexity of cytometry
      experiments (more cells and more markers), traditional manual flow cytometry data
      analysis has become untenable due to its subjectivity and time-consuming nature.
      We present a new unsupervised algorithm called "cytometree" to perform automated
      population identification (aka gating) in flow cytometry. cytometree is based on
      the construction of a binary tree, the nodes of which are subpopulations of
      cells. At each node, the marker distributions are modeled by mixtures of normal
      distributions. Node splitting is done according to a model selection procedure
      based on a normalized difference of Akaike information criteria between two
      competing models. Post-processing of the tree structure and derived populations
      allows us to complete the annotation of the populations. The algorithm is shown
      to perform better than the state-of-the-art unsupervised algorithms previously
      proposed on panels introduced by the Flow Cytometry: Critical Assessment of
      Population Identification Methods project. The algorithm is also applied to a T
      cell panel proposed by the Human Immunology Project Consortium (HIPC) program; it
      also outperforms the best unsupervised open-source available algorithm while
      requiring the shortest computation time. (c) 2018 International Society for
      Advancement of Cytometry.

PMID- 30277650
TI  - Epoxy Isonitriles, A Unique Class of Antibiotics: Synthesis of Their Metabolites
      and Biological Investigations.
AB  - Epoxy isonitrile containing natural products often possess specific and potent
      antibacterial activity against Gram-positive pathogens. This scaffold, however,
      is extremely labile under acidic and basic conditions, undergoing a Payne
      rearrangement to produce a stable epoxy ketone metabolite and releasing hydrogen
      cyanide. We synthesized and performed biological assays with epoxy ketone
      containing metabolites and identified that the epoxy isonitrile moiety is
      pertinent for biological activity. Serendipitously, we discovered an alpha,beta
      unsaturated epoxy ketone analogue that exhibited moderate activity against
      Staphylococcus aureus.

PMID- 30277652
TI  - Novel Rapid Screening of Basic Immobilized Amine Sorbent/Catalyst Water Stability
      by a UV/Vis/Cu2+ Technique.
AB  - Time-consuming thermogravimetric analysis (TGA) decomposition study is a typical
      practice to assess the stability of fresh and water-treated basic immobilized
      amine sorbents (BIAS)/catalysts. This work presents a faster and more precise
      spectroscopic UV/Vis/Cu2+ sorbent screening technique that quantifies aqueous
      amines washed from the BIAS by using UV-active amine/Cu2+ complexes. Six BIAS
      based catalysts, containing different amine species and a crosslinker within
      silica, were treated with ultrapure water and then analyzed for their CO2 capture
      performance and amine leach resistance/stability by using TGA (catalysts,
      approximately 4 h) and UV/Vis/Cu2+ techniques (wash solution, few minutes). A
      comparative analysis revealed that directly quantifying washed amines with
      UV/Vis/Cu2+ is 9-127 times more precise than indirect testing of the sorbents by
      TGA. Similar trends in the H2 O stability profiles of the catalysts [organic
      content retained values (OCR)] were reported by both analysis methods, allowing
      UV/Vis/Cu2+ to replace TGA for quantifying unstable leached amines. The
      UV/Vis/Cu2+ OCR results could be used to predict the CO2 -capture stability
      profile of the sorbents, confirming the reliability of this technique to rapidly
      screen catalyst stability and performance.

PMID- 30277651
TI  - Identification of LEA, a podocalyxin-like glycoprotein, as a predictor for the
      progression of colorectal cancer.
AB  - Large external antigen (LEA) is considered as a colorectal cancer (CRC)
      associated antigen, which was found via mAb ND-1 generated using hybridoma
      technology, but its molecular features remain unknown. To facilitate the clinical
      application of LEA, we identified LEA as a podocalyxin-like protein 1 (PODXL)
      with molecular weight of approximately 230 kDa, a hyperglycosylated protein,
      using immunoprecipitation and mass spectrometry in combination, and verified that
      ND-1-recognized epitope is on the terminal sialic acid of LEA. Correlation
      analysis between LEA and PODXL in molecular weight, immunological cross
      reactivity, and gene expression dependence supported the PODXL identity of the
      LEA. Moreover, we assessed the clinical significance of the LEA in 89 pairs of
      primary CRC tissues and adjacent nontumor colorectal tissues using ND-1 by
      quantum dot-based immunohistochemistry (QD-IHC). High LEA expression was
      correlated significantly with T stage (P = 0.010). Patients with high LEA
      expression showed significantly poorer prognosis than those with LEA low
      expression (P = 0.007). Multivariate analysis indicated LEA expression as an
      independent predictor. Furthermore, the comparative analysis showed that mAb ND-1
      based IHC analysis toward sugar residue of PODXL has higher sensitivity and
      specificity to evaluate the LEA/PODXL expression than mAb 3D3-based method toward
      core protein of PODXL in CRC cell lines and clinical samples. In addition, we
      first found that LEA/PODXL can be secreted in exosomes from cancer cells and CRC
      patient peripheral blood. Our results demonstrate that LEA is an independent
      predictor for CRC progression and has the potential to be applied for clinical
      setting with high sensitivity, high specificity, and noninvasive access.

PMID- 30277653
TI  - Pattern of distant metastases in primary extrahepatic bile-duct cancer: A SEER
      based study.
AB  - Extrahepatic bile duct cancer (EBDC) is a combined type of malignancy mainly
      consisting of extrahepatic cholangiocarcinoma and gallbladder cancer. Clinically,
      it is featured with latent symptoms and early metastasis, leading to a poor
      prognosis. Therefore, this cohort study aimed to depict the possible metastatic
      patterns of EBDC of diverse sub-types and evaluate the prognostic significance of
      diverse metastatic destinations with data from the clinical database. Relevant
      data of total 4061 confirmed EBDC patients diagnosed between 2010 and 2013 from
      the Surveillance, Epidemiology and End Results (SEER) database was obtained. We
      applied t test to describe the baseline data of patients included and used chi
      square test to compare the distribution of distant metastatic sites. We further
      adopted odds ratio assess the combined metastatic patterns and compared survival
      difference of patients with different distal metastasis organ by Kaplan-Meier
      analysis. We identified totally 4061 patients over 18 years old diagnosed with
      extrahepatic bile tract malignancies between 2010 and 2013, with clear metastatic
      status and follow-up data, without primary malignancies. Liver and distant lymph
      (DL) are the two most common sites as a single metastasis organ. In combined
      metastasis patterns, bi-organ is more frequent than the other types. Lung is the
      organ preferentially for bi-organ metastasis, while bone and distant lymph
      similarly intend to co-metastasize with brain. Distal metastasis in EBDC patients
      indicates an extremely poor prognosis. According to the final analysis results,
      malignancies in extrahepatic bile duct exhibit similar metastatic patterns,
      suggesting that we can regard them as a unity to assess its development. Profound
      differences exist in distribution of distant extrahepatic metastatic sites and
      their combinations. Results from our studies would provide some information for
      follow-up strategies and future studies.

PMID- 30277655
TI  - First-in-Human Studies for a Selective RET Tyrosine Kinase Inhibitor, GSK3179106,
      to Investigate the Safety, Tolerability, and Pharmacokinetics in Healthy
      Volunteers.
AB  - Rearranged during transfection (RET), a neuronal growth factor receptor tyrosine
      kinase, regulates the development of the sympathetic, parasympathetic, motor, and
      sensory neurons in the enteric nervous system. GSK3179106 is a RET kinase
      inhibitor that was administered in double-blind, randomized, placebo-controlled
      single-dose and repeat-dose studies in healthy subjects to investigate its
      pharmacokinetics and safety/tolerability. In the single-dose study (n = 16),
      GSK3179106 was dosed from 10 mg to 800 mg, including a food effect arm. In the
      repeat-dose study (n = 46), GSK3179106 was dosed for 14 days with food once daily
      (QD) from 5 mg to 100 mg and twice daily (BID) at 100 mg and 200 mg. With single
      fasted doses, bioavailability was low and less than dose proportional. A
      significant food effect was observed with a 100-mg QD dose. Drug exposure after
      QD and BID repeat dosing with food showed dose dependency up to 100 mg but was
      not dose proportional. There were no significant differences in exposure between
      100-mg and 200-mg BID doses of GSK3179106. Accumulation was observed with both QD
      and BID dosing. Single doses up to 800 mg and repeat doses up to 400 mg were well
      tolerated with no safety concerns in healthy subjects.

PMID- 30277654
TI  - Gamma-aminobutyric acid transaminase genetic polymorphism is a candidate locus
      for responsiveness to opioid analgesics in patients with cancer pain: An
      exploratory study.
AB  - AIM: Cancer pain impairs not only physical functions but also social functions
      and roles. Consequently, the overall health-related quality of life of patients
      with cancer pain deteriorates. Opioid analgesics are recommended for treating
      moderate to strong cancer pain. Advances in human genome research have fueled a
      growing interest to understand individual differences in responsiveness to opioid
      analgesics. This study aimed to explore and identify novel loci for genes
      predisposing an individual to opioid analgesic responsiveness. METHODS: A total
      of 71 cancer patients rated their pain on an 11-point numerical rating scale
      twice before and after increasing opioid analgesics. A genomewide association
      study focusing on single nucleotide polymorphisms (SNPs) was conducted to
      associate pain decrease with increased dosage of opioid analgesics based on
      weight (ie, responsiveness to opioid analgesics). A genomewide significance (P <
      5E-8) was set for multiplicity of analyses to control for false positives.
      RESULTS: Two SNPs passed the genomewide threshold for significance. One exonic
      SNP (rs1641025) was located in the ABAT [4-aminobutyrate aminotransaminase (GABA
      transaminase)] gene on chromosome 16. The other SNP (rs12494691) was located on
      chromosome 3, which was not associated with any known genes. These SNPs were not
      associated with opioid-related adverse effects. CONCLUSIONS: Our results
      preliminarily suggest that both SNPs might be potential candidate loci for
      responsiveness to opioid analgesics, and GABA transaminase might be a possible
      target for developing adjuvant pharmacotherapy with opioid analgesics in adjuvant
      pharmacotherapy. Our results should be validated in a large-scale study with a
      larger sample size.

PMID- 30277656
TI  - Where to "cut-off"?

PMID- 30277657
TI  - Mind perception and moral judgment in autism.
AB  - Social difficulties of autistic individuals have been suggested to be caused by
      mind blindness, the absence of a theory of mind. Numerous studies have
      investigated theory of mind in autism spectrum disorder or how autistic
      individuals represent the mental states of others. Here, we have examined, as an
      alternative, mind perception, namely how individuals perceive the minds of
      various animate and inanimate entities. Autistic and non-autistic participants
      demonstrated evidence of a similar two-dimensional mind perception; agency,
      capacity for doing (i.e., self-control, memory, plan), and experience, capacity
      for feeling (i.e., fear, hunger, pain). Some targets (e.g., human infant and dog)
      were perceived to have low agency but high experience, while others (e.g., robot
      and God) were perceived to have the reverse pattern. Moreover, in both autistic
      and non-autistic groups, the attribution of moral blame positively correlated
      with agency, whereas moral consideration positively correlated with experience.
      These results offer new evidence of social cognition, particularly conception of
      mind and morality, in autism. Autism Res 2018, 11: 1239-1244. (c) 2018
      International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY:
      We found that autistic and non-autistic individuals have similar thoughts
      regarding the minds of various living and nonliving entities. In addition, both
      groups gave moral consideration or blamed entities for wrongdoing according to
      their conception of the minds of those entities. Autistic individuals have this
      mind-based moral sense, which is a pivotal element with a key role in human
      society.

PMID- 30277658
TI  - The anatomy of single cell mass cytometry data.
AB  - Mass cytometry enables the measurement of up to 50 features on single cell. This
      has catalyzed a shift toward multidimensional data analysis methods, rather than
      the manual gating strategies as traditionally for in flow cytometry data. This
      shift means that data scientists are involved in the analysis process to an
      increasing degree. As the data is analyzed in a more unbiased fashion, where
      noisy or uninformative observations are not easily excluded, a deeper knowledge
      of the origin, noise, and modalities of the data is therefore needed to embark on
      useful data analysis. In this primer, we introduce the idiosyncrasies of mass
      cytometry data with a focus on the technical properties of how data generated
      with the CyTOF(r) system, and the characteristics of protein expression in the
      cells of the hematopoietic continuum, specifically targeted toward data
      scientists. We also provide a comprehensive online repository of scripts,
      tutorials, and example data.

PMID- 30277659
TI  - Temperature Difference Triggering Controlled Growth of All-Inorganic Perovskite
      Nanowire Arrays in Air.
AB  - All-inorganic perovskites have attracted increasing worldwide interest due to its
      significantly improved stability in atmospheric environment compared to organic
      inorganic hybrid perovskites, which renders it infinitely applicable in many
      fields such as electronics, optoelectronics, and energy storage. However, all
      inorganic perovskites have to confront the challenges from fabrication before
      their wide utilization in the aforementioned applications. Liquid-phase synthesis
      holds the advantage of mass production and easy modulation of composition but
      with the deficiencies of relatively low crystallinity and disordered products.
      Interestingly, gas-phase growth has complementary characteristics compared to the
      liquid-phase method. In this work, it is proposed that a novel temperature
      difference triggers growth strategy to integrate the merits of the liquid- and
      gas-phase methods, and the feasibility of this strategy via a simple lab-use hot
      plate is demonstrated. High quality all-inorganic perovskites, cesium lead halide
      (CsPbX3 ) nanowire arrays, can be epitaxially grown as in a gas-phase method, but
      at the same time, the composition of products can be easily modulated by
      predesigning the recipe of precursors as in the liquid-phase method on a large
      scale. Notably, the as-fabricated CsPbX3 perovskite nanowire arrays demonstrate
      excellent stability and good optoelectronic properties in air. It is believed
      that this novel strategy can strikingly prompt the development of perovskites
      fabrication and applications in future.

PMID- 30277660
TI  - The RareCyte(r) platform for next-generation analysis of circulating tumor cells.
AB  - Circulating tumor cells (CTCs) can reliably be identified in cancer patients and
      are associated with clinical outcome. Next-generation "liquid biopsy"
      technologies will expand CTC diagnostic investigation to include phenotypic
      characterization and single-cell molecular analysis. We describe here a rare cell
      analysis platform designed to comprehensively collect and identify CTCs, enable
      multi-parameter assessment of individual CTCs, and retrieve single cells for
      molecular analysis. The platform has the following four integrated components: 1)
      density-based separation of the CTC-containing blood fraction and sample
      deposition onto microscope slides; 2) automated multiparameter fluorescence
      staining; 3) image scanning, analysis, and review; and 4) mechanical CTC
      retrieval. The open platform utilizes six fluorescence channels, of which four
      channels are used to identify CTC and two channels are available for
      investigational biomarkers; a prototype assay that allows three investigational
      biomarker channels has been developed. Single-cell retrieval from fixed slides is
      compatible with whole genome amplification methods for genomic analysis.

PMID- 30277661
TI  - "Print-to-pattern": Silk-Based Water Lithography.
AB  - The requirement of nontoxic and versatile manufacturing frameworks for
      biologically relevant applications has imposed significant constraints on the
      choice of functional materials and the complementary fabrication tools. In this
      context, silk is actively studied, thanks to its mechanical robustness,
      biocompatibility, wide availability, aqueous processing conditions, and ease of
      functionalization. The inherent matching between the water solubility of silk and
      the aqueous inks of the inkjet printing (IJP) process has derived a biofriendly
      and versatile "print-to-pattern" scheme-termed silk-based water lithography
      toward scalable functional biomanufacturing. The deposition mode of IJP and the
      etching effect of silk film by water features a dual tone fabrication where
      functional molecules are dispensed additively, while the silk film is patterned
      in a "subtractive" fashion. Such versatility and scalability pave the way to a
      wide range of opportunities in the biomedical field.

PMID- 30277662
TI  - Combining fluorescent cell barcoding and flow cytometry-based phospho-ERK1/2
      detection at short time scales in adherent cells.
AB  - Detection of levels of intracellular phospho-proteins is key to analyzing the
      dynamics of signal transduction in cellular systems. Cell-to-cell variability in
      the form of differences in protein level in each cell affects signaling and is
      implicated in prognosis of many diseases. Quantitative analysis of such
      variability necessitate measuring the protein levels at single-cell resolution.
      Single-cell intracellular protein abundance detection in statistically
      significant number of adherent cells for short time sampling points post
      stimulation using classical flow cytometry (FCM) technique has thus far been a
      challenge due to the detrimental effects of cell detachment methods on the
      cellular machinery. We systematically show that cell suspension obtained by
      noninvasive temperature-sensitive detachment of adherent cells is amenable to
      high-throughput phospho-ERK1/2 protein detection at single-cell level using FCM
      in these short time sampling points. We demonstrate this on three adherent cell
      lines, viz., HeLa, A549, and MCF7, from distinct lineages having
      characteristically different elasticity at 37  degrees C. In particular, we use a
      right combination of multiplexing via fluorescent cell barcoding (FCB) and
      intracellular antibody staining for simultaneous detection of phospho-ERK1/2
      (pERK) stimulated by epidermal growth factor (EGF) in multiple samples. Based on
      systematic characterization using Alexa 350 dye, we arrive at two conditions that
      must be satisfied for correct implementation of FCB. Our study reveals that the
      temperature-sensitive detachment of HeLa cells correctly captures the expected
      pronounced bimodal pERK distribution as an early response to EGF, which the
      enzymatic treatment methods fail to detect.

PMID- 30277663
TI  - A shared effect of paroxetine treatment on gray matter volume in depressive
      patients with and without childhood maltreatment: A voxel-based morphometry
      study.
AB  - AIMS: This study assessed whether antidepressant drug treatment has a common
      effect on gray matter (GM) volume in MDD patients with and without childhood
      maltreatment (CM). METHODS: T1-weighted structural magnetic resonance imaging
      data were collected from 168 participants, including 51 MDD patients with CM, 31
      MDD patients without CM, 48 normal controls with CM, and 38 normal controls
      without CM. MDD patients received 6 months of treatment with paroxetine, and 24
      patients with CM, and 16 patients without CM received a second MRI scan. A whole
      brain voxel-based morphometry approach was used to estimate GM volume in each
      participant at two time points. Two-way analysis of variance (ANOVA) was used to
      determine the effects of MDD and CM on GM volume at baseline. Repeated measures
      two-way ANOVA was used to determine the treatment-by-CM interactive effect and
      main effect of treatment during paroxetine treatment. We further investigated the
      relationship between GM volume and clinical variables. RESULTS: At baseline,
      significant MDD-by-CM interactive effects on GM volume were mainly observed in
      the left parahippocampal gyrus, left entorhinal cortex, and left cuneus. GM
      volume was significantly lower mainly in the right middle temporal gyrus in
      patients with MDD than in normal controls. We did not find any significant
      treatment-by-CM interactive effects. However, a treatment-related increase in GM
      was found in the right middle temporal gyrus in both MDD groups. CONCLUSIONS:
      These results suggest that paroxetine treatment operates via a shared
      neurobiological mechanism in MDD patients with and without CM.

PMID- 30277665
TI  - Small-Sized Cationic miRi-PCNPs Selectively Target the Kidneys for High
      Efficiency Antifibrosis Treatment.
AB  - Small-sized cationic miRi (microRNA-21 inhibitor)-PCNPs (low molecular weight
      chitosan (LMWC)-modified polylactide-co-glycoside (PLGA) nanoparticles (PLNPs))
      with special kidney-targeting and high-efficiency antifibrosis treatment are
      fabricated through coupling miRi, PLGA, and LMWC. In the miRi-PCNPs, easily
      degraded miRi is encapsulated in PCNPs and thus prevented from degradation by
      nuclease. Cytotoxicity, immunotoxicity, and systemic toxicity assays and in vitro
      and ex vivo fluorescence imaging suggest that PCNPs possess excellent
      biocompatibility, higher cellular uptake efficiency, and selective kidney
      targeting capacity. Western blotting, pathological staining, and real-time
      polymerase chain reaction analyses show that the therapeutic effect of miRi-PCNPs
      on kidney fibrosis is much higher than that of miRi, which is mainly through
      suppressing transforming growth factor beta-1/drosophila mothers against
      decapentaplegic protein 3 (TGF-beta1/Smad3) and extracellular signal-regulated
      kinases/mitogen-activated protein kinase signaling pathway by inhibiting the
      expression of microRNA-21. For example, the tubule damage index and
      tubulointerstitial fibrosis area in the miRi-PCNPs group are ~2.5-fold lower than
      those in the saline and bare miRi groups. The miRi-PCNPs with special kidney
      targeting and high-efficiency antifibrosis treatment may represent a promising
      strategy for designing and developing a therapeutic treatment for kidney
      fibrosis.

PMID- 30277666
TI  - Studies on selected molecular factors in endometrial cancers.
AB  - BACKGROUND: Endometrial carcinomas (EC) differ in etiology, clinical course and
      prognosis. OBJECTIVES: This multi-center study aimed at a closer recognition of
      molecular factors linked to heterogeneity of EC by evaluating estrogen and
      progesterone receptors, proteins dependent on MMR genes, proteins linked to poor
      prognosis and metastases, and mutations in BRCA1. MATERIAL AND METHODS: Using
      sections of paraffin-embedded preparations, in 115 patients with EC type I and 31
      with EC type II, expression of ERalpha, ERbeta1, PR, MLH1, and MSH2 proteins, as
      well as ARID1A, c-MET and BRCA1, was estimated by immunohistochemistry using
      specific antibodies. RESULTS: Expression of ERbeta1 was augmented in EC type II,
      in poorly differentiated cancers and with growing clinical advancement. An
      augmented expression of ERalpha was noted in well-differentiated EC and at lower
      clinical stage. An increased expression of PR and decreased of MLH1 were detected
      in type I EC. The expression of ARID1A and c-MET proteins showed no differences
      between the types of EC, stages of clinical advancement or grading. In 51.6%
      patients with type II EC, a loss of BRCA1 expression was disclosed; in this group
      of cancers a decreased expression of ERalpha was noted. CONCLUSIONS: An augmented
      expression of ERbeta1 was linked to type II EC. A higher expression of ERalpha in
      EC cancers was associated with a lower histopathological grade. A decreased
      expression of MLH1 protein was estimated in EC type I. Type II EC may be
      connected to BRCA1 mutation.

PMID- 30277664
TI  - Circular RNAs: Methodological challenges and perspectives in cardiovascular
      diseases.
AB  - Circular RNAs are generated by back-splicing of precursor-mRNAs. Although they
      have been known for many years, only recently we have started to appreciate their
      widespread expression and their regulatory functions in a variety of biological
      processes. Not surprisingly, circular RNA dysregulation and participation in the
      pathogenic mechanisms have started to emerge in many instances, including
      cardiovascular diseases. Detection, differential expression analysis and
      validation are the three critical points for the characterization of any RNA, and
      circular RNAs are no exception. Their characteristics, however, generate several
      problems that are yet to be completely addressed, and literature still lacks
      comprehensive definitions of well-defined best practices. We present a map of the
      current knowledge regarding circular RNAs and the critical issues limiting our
      understanding of their regulation and function. The goal was to provide the
      readers with the tools to critically decide which of the many approaches
      available is most suitable to their experimental plan. Although particularly
      focused on cardiovascular diseases, most critical issues concerning circular RNAs
      are common to many other fields of investigation.

PMID- 30277667
TI  - ALOX12 gene polymorphisms and serum selenium status in elderly osteoporotic
      patients.
AB  - BACKGROUND: Osteoporosis is a systemic bone disease which leads to a reduction in
      bone mass. Many studies have shown that up to 80% of bone mineral density (BMD)
      variations are attributed to genetic factors. Arachidonate 12-lipoxygenase
      enzyme, encoded by the ALOX12 gene, produces lipid peroxides as reactive oxygen
      species (ROS), leading to oxidative stress and the development of osteoporosis.
      Selenium (Se) is incorporated into selenoproteins, which may reduce the risk of
      osteoporosis. OBJECTIVES: We aimed to investigate the association of 2 ALOX12
      single nucleotide polymorphisms (SNPs) and serum Se level with lumbar spine and
      femoral neck BMD among elderly individuals living in Amirkola, Iran. MATERIAL AND
      METHODS: The study consisted of 180 individuals aged >=60 years (90 healthy and
      90 osteoporotic patients). We examined the effect of 2 ALOX12 SNPs (rs2292350 and
      rs9897850), using the polymerase chain reaction - restriction fragment length
      polymorphism (PCR-RFLP) on both BMD regions measured by dual energy X-ray
      absorptiometry (DXA). Serum Se level was measured using an atomic absorption
      spectrophotometer PGG990 AAS (PG Instruments Ltd., Luterworth, USA). RESULTS: The
      rs2292350 SNP showed a significant association with femoral neck BMD (p = 0.04).
      Moreover, in terms of serum Se level, a significant difference was found between
      the patient group (57.58 +/-25.54 MUg/L) and the control group (81.09 +/-25.58
      MUg/L) (p < 0.001). In addition, individuals with higher serum Se levels also had
      higher BMD of the lumbar spine (r2 = 0.392; p < 0.001) and the femoral neck (r2 =
      0.478; p < 0.001). CONCLUSIONS: The results suggested that genetic variation in
      ALOX12 might influence BMD variations in our recruited participants. As for the
      patients with lower serum Se levels, it was observed that serum Se deficiency was
      accompanied by some ALOX12 variation, contributing to the development of
      osteoporosis.

PMID- 30277668
TI  - Clinical-pathological characteristics of patients treated for cancers of the
      eyelid skin and periocular areas.
AB  - BACKGROUND: Malignant cancers of the eyelid skin and the periocular area comprise
      5-10% of facial skin malignant cancers. Basal cell carcinomas (BCCs) dominate,
      comprising approx. 80-90% of cancers of this area of the face. Considerably less
      often, in 9-14% of cases, squamous cell carcinomas (SCCs) are observed.
      OBJECTIVES: The aim of this study is to provide an epidemiological-clinical
      assessment of patients treated over the period 2006-2015 for primary malignant
      cancers of the eyelid skin considering histological diagnosis and clinical
      staging. MATERIAL AND METHODS: This study was based on an analysis of the medical
      records of 262 patients. Demographic data, age, sex, size and location of
      lesions, histological types, and clinical staging were assessed. RESULTS: In the
      analyzed group of 262 patients, most were over the age of 60 years. Primary
      cancers were most frequently located in the area of the medial canthus of the eye
      and in the lower eyelid skin. They were mainly lesions of 6-10 mm and 16-20 mm
      with histologically diagnosed basal cell carcinoma of nodular and cystic types.
      CONCLUSIONS: The most represented group was that of patients aged 60-70 years
      with primary cancers located in the medial canthus of the eye (47.3%) and in the
      lower eyelid. Basal cell carcinoma was diagnosed, mainly nodular and cystic
      types.

PMID- 30277669
TI  - Do CTRC mutations affect the development of alcoholic chronic pancreatitis and
      its course among Poles: Preliminary study.
AB  - BACKGROUND: Genetic mutations are one of the etiological factors that predispose
      people to develop chronic pancreatitis. OBJECTIVES: The aim of our study was to
      examine the effect of p.Trp55*, p.Arg254Trp and c.738_761del mutations in the
      chemotrypsin gene (CTRC) on the development of alcoholic chronic pancreatitis
      (ACP) in order to answer the questions whether these mutations vary between
      gender groups, whether they were related to the age when ACP was first diagnosed,
      and whether they affected the morphological changes in the pancreas and the
      course of ACP. MATERIAL AND METHODS: The study included 124 patients with ACP, 52
      with nonalcoholic pancreatitis and 52 controls. The p.Trp55*, c.738_761del and
      p.Arg254Trp mutations in the CTRC gene were tested by the polymerase chain
      reaction (PCR). RESULTS: The c.738_761del and p.Arg254Trp mutations occurred in
      3.07% and 1.31% of cases, respectively. None of the examined patients were found
      to have the p.Trp55* mutation. The frequency of detected mutations did not
      significantly differ between the study groups. The c.738_761del mutation was
      detected more frequently in women than in men. No significant differences were
      found in the age at ACP onset, morphological changes affecting the pancreas, or
      in the course of ACP between the patients with and without the 2 examined
      mutations. The c.738_761del mutation was significantly more frequent in the
      diabetic patients than in the non-diabetics. The patients with this mutation more
      frequently required surgery than those without the c.738_761del mutation.
      CONCLUSIONS: No relationship between the c.738_761del and p.Arg254Trp mutations
      and the development of APC was found. The c.738_761del mutation was more frequent
      in females than in males. Neither mutation affected the patient's age at ACP
      onset or its course. In contrast to p.Arg254Trp, the c.738_761del mutation
      correlated with diabetes development and the need for surgery in the course of
      ACP.

PMID- 30277670
TI  - Diseases of the oral cavity in light of the newest epigenetic research: Possible
      implications for stomatology.
AB  - Epigenetics is the study of inheritable changes in gene expression without
      changes in the underlying deoxyribonucleic acid (DNA) sequence. The main
      mechanisms of epigenetic regulation include DNA methylation, modifications in
      histones, and micro-ribonucleic acids (miRNA). Recent research evidence has shown
      that environmental and lifestyle factors dynamically interact with the genome,
      influencing epigenetic changes, from development to the later stages of life.
      This happens across a spectrum, from physiological to pathological conditions,
      such as genetic defects, developmental disorders, infectious or inflammatory
      processes, cancers, mental disorders, and substance abuse. Epigenetic studies
      have been conducted in various medical disciplines (e.g., oncology, internal
      medicine or psychiatry), adding valuable insight to standard medical approaches.
      However, in stomatology, epigenetic research is still in its infancy; thus, this
      review is aimed at presenting the role of epigenetic mechanisms in diseases of
      the oral cavity, including periodontal diseases, caries, developmental anomalies,
      and oral carcinoma. In addition, this paper reveals new insights into epigenetic
      biomarkers that can be helpful in the detection, early diagnosis, prognosis, and
      treatment of different oral diseases. Moreover, this review is focused on the
      possible clinical implications (diagnostic and therapeutic) of epigenetics, in
      the form of some noninvasive methods that can possibly be used in the future for
      the screening, work-up, outcome prediction and novel treatments of some dental
      diseases. Finally, this paper highlights that an epigenetic approach can be
      useful for designing novel interventions that will improve the management of oral
      malignancies or developmental abnormalities.

PMID- 30277671
TI  - The journey of the heart failure patient based on data from a single center.
AB  - BACKGROUND: Care for patients with heart failure (HF) in Poland requires
      improvement. OBJECTIVES: The aim of this study was to define the journey of a HF
      patient, taking into account the specialization of the hospital ward and further
      highly specialized outpatient care. MATERIAL AND METHODS: Using the medical
      system CliniNET(r) we analyzed 214 consecutive patients hospitalized due to HF
      (ICD-10: I50) in the period from September 1, 2015, to December 31, 2015, and
      also the data from post-discharge outpatient care in a 3-month period. To fairly
      compare the management of care and outcomes of patients hospitalized in internal
      medicine (IM) ward and in cardiac ward, propensity score matching was performed.
      The multivariate regression analysis was performed to determine the independent
      predictors of the hospital ward selection and risk of rehospitalization due to HF
      and/or death. RESULTS: The majority of patients were hospitalized due to HF for
      the first time (72%) and in the cardiac ward (65%). For 55% of rehospitalized
      patients the subsequent admission was within 3 months post-initial discharge. The
      independent predictors of a higher risk of rehospitalization due to HF and/or
      death were ischemic heart disease, atrial fibrillation (AF), chronic kidney
      disease (CKD), mineralocorticoid antagonism (MRA) therapy, and hospitalization in
      the last year (all p < 0.05). Internal medicine ward patients differed from
      cardiac ward patients in: mode of admission (urgent 100% vs 83.5%; p < 0.001),
      length of hospitalization (median 8 vs 5 days; p = 0.001), death rate (24% vs
      4.3%; p < 0.001), echocardiography (43% vs 98%; p < 0.001), and NT-proBNP
      measurements (43% vs 96%; p < 0.001). The burden of 5-9 accompanying diseases
      enhanced the choice of the cardiac ward (p < 0.05), while age and urgent mode of
      hospitalization decreased the chance of being referred to the cardiac ward (p <
      0.01). Cardiac patients were more likely to receive beta-blockers, diuretics,
      angiotensin receptor blockers (ARB) and MRA. Over 90% of cardiac ward patients
      were referred to cardiac ambulatory care after discharge from the hospital, while
      among patients discharged from IM ward this rate was 60% (p < 0.001).
      CONCLUSIONS: There were significant differences among the 2 wards in relation to
      the course of hospitalization and post-discharge outpatient care.

PMID- 30277672
TI  - Withholding and withdrawing life-sustaining treatment: Experiences in limiting
      futile therapy from three Polish intensive care departments.
AB  - BACKGROUND: In intensive care units (ICUs), a patient's vital functions may be
      maintained, regardless of the patient's chances of survival. A key issue is how
      to precisely determine the moment in which life-support treatment should be
      withheld. In many countries, the decision-making process is regulated by the
      guidelines of scientific societies. However, heuristic errors may influence this
      process. OBJECTIVES: The objective of this study was to assess factors involved
      in decisions to implement or withhold treatment in general ICUs in Poland.
      MATERIAL AND METHODS: The medical records of patients treated in 3 clinical ICUs
      of general, cardiosurgical and neurosurgical profile were retrospectively
      analyzed. Patients with a diagnosis of brain death were finally excluded from the
      study. RESULTS: The records of 1,449 patients hospitalized between January 1,
      2014 and December 31, 2014 were analyzed. Of these, 226 patient cases were
      evaluated. There were no correlations between the placement of restrictions on
      resuscitation in specific cases, use of noradrenaline, frequency of blood gas
      testing, and patients' age. There was a relationship between these factors and
      the duration of hospitalization in the ICU. There was a direct relation between a
      "do not resuscitate" (DNR) order in a patient's record and the frequency of both
      resuscitation procedures and withholding catecholamine treatment in the hours
      preceding a patient's death. CONCLUSIONS: Treatment was withheld in about 20% of
      cases involving dying patients in analyzed ICUs, regardless of age. Placing a
      limit on treatment consisted of either withholding new procedures or withdrawing
      existing therapy. The length of stay in the ICU affected the decisions to limit
      treatment.

PMID- 30277673
TI  - Thymoma and Limbic Encephalitis: A Dangerous Liaison.

PMID- 30277674
TI  - Examining Symptom Clusters of Childbirth-Related Posttraumatic Stress Disorder.
AB  - Objective: Recent studies document posttraumatic stress disorder (PTSD) symptoms
      in women following at-term deliveries with health baby outcomes. However, the
      notion that childbirth can trigger PTSD remains controversial, and the symptom
      clusters are mostly unknown. The objective of this study was to examine the
      clustering of childbirth-induced postpartum PTSD (PP-PTSD) symptoms in comparison
      to DSM-5 clusters. Methods: We examined the symptom presentation of childbirth
      related postpartum PTSD (PP-PTSD) in a sample of 685 women. The majority of these
      women delivered at term. Peritraumatic stress reactions to childbirth and PP-PTSD
      symptoms were assessed approximately 3 months after delivery. A hierarchical
      cluster analysis was used to detect grouping of the PP-PTSD symptoms. Results:
      Childbirth-related peritraumatic stress was strongly and positively associated
      with PP-PTSD symptom severity. Cluster modeling revealed 4 distinguished symptom
      groups: reliving (some reexperiencing symptoms), namely nightmares and
      flashbacks; avoidance coupled with unwanted memories (other reexperiencing
      symptoms); negative cognitions and mood; and hyperarousal reactivity.
      Conclusions: Our findings show that the representation of symptoms of PTSD that
      develops following a stressogenic childbirth experience appears, for the most
      part, to resemble DSM-5 symptom clusters. More research integrating descriptive
      symptom assessment with biological measures is warranted to better characterize
      the symptom presentation of this neglected posttraumatic stress syndrome.

PMID- 30277675
TI  - [Nursing University Education in a New Healthcare Setting].
AB  - Nursing university education has to respond to the challenges of the 21st
      century. Health conditions are highly complex with associated social problems.
      The universities should train nurses with a transforming vision, by defining
      study plans, preventive approach and promoting health, in a context of community
      health. The information and communication technologies along with the nurse
      leadership are also essential elements of value for graduated nurses. An
      innovative response to social needs and transformation of society requires
      commitment in defining the study plans of degree and also in the master's degree
      and in the continuing education programs. Investigate is how to acquire the
      necessary skills to generate knowledge to help ensure the professional
      development of nurses and contribute to the persons health.

PMID- 30277676
TI  - [Disseminated Cryptococcosis with Eosinophilia and Elevated IgE in a Non-HIV
      infected Patient].
AB  - In general, disseminated cryptococcosis usually occurs among immunocompromised
      patients, especially those with cell-mediated immunodeficiency, such as HIV
      infected patients. We present herein a rare case of an apparently immunocompetent
      33-year-old woman who developed disseminated cryptococcal diseases, which
      included meningitis and pneumonia with eosinophilia, and pulmonary tuberculosis
      during her disease course. Pneumonia with a diffuse micronodular pattern,
      immediately followed by meningitis, was diagnosed as disseminated cryptococcosis,
      because of the presence of yeast-like-fungi demonstrated by transbronchial lung
      biopsy and a positive cerebrospinal fluid (CSF) culture. In addition, the
      pneumonia exhibited eosinophilia in the peripheral blood and bronchoalveolar
      lavage fluid. Re-exacerbation of the pneumonia occurred approximately 3 weeks
      after onset, along with a sputum culture positive for Mycobacterium tuberculosis.
      Administration of anti-tuberculosis drugs resulted in recovery from the pulmonary
      tuberculosis. The treatment of cryptococcal meningitis was initiated using a
      standard induction regimen;however, an unrecovered status, highlighted by
      elevated CSF pressure, persisted. Finally, full recovery was induced by the
      addition of flucytosine treatment (100 mg/kg/day) and repeated daily via lumbar
      puncture. The allergic condition of this patient may have contributed to the
      onset of disseminated cryptococcosis.

PMID- 30277677
TI  - [A Case Diagnosed Toxocariasis After the Intiation of Treatment with Steroids for
      Eosinophilic Granulomatosis with Polyangitis (EGPA)].
AB  - Toxocariasis causes a variety of symptoms. We experienced a case of toxocariasis
      which was initially treated with steroids for Eosinophilic Granulomatosis with
      Polyangitis (EGPA).A 53-year-old woman with the past medical history of bronchial
      asthma presented at the outpatient department in the middle of August. She
      complained of chest discomfort lasting for one week. Ischemic heart disease was
      initially suspected due to ST depression on ECG and positive Troponin I. However
      coronary angiography did not reveal any abnormality. Her symptoms continued and
      after one month she presented at the hospital again with an elevated eosionophil
      count. Chest computed tomography showed ground glass opacities on both lungs. She
      was diagnosed as having EGPA based on her clinical symptoms and the results of
      the blood test which were consistent with the diagnostic criteria of EGPA. After
      prednisolone was prescribed, her symptoms and eosinophilia dramatically improved.
      However, we found that the histology of the lung and kidney was not compatible
      with EGPA and the result of serum parasite antibodies turned out to be strongly
      positive for toxocariasis after initiating predonisolone.Based on this result, we
      concluded that our patient had a case of toxocariasis and prescribed albendazole
      in addition to prednisolone. The patient completed a 3-week course of albendazole
      and a 3-month course of prednisolone without any problems. In general, steroids
      are not commonly used as a treatment of toxocariasis, however it seems to have
      been effective in this case. Toxocariasis shows a variety of symptoms and can be
      misdiagnosed as other diseases such as EGPA.

PMID- 30277678
TI  - [Introduction of a Hand-hygiene Automated Monitoring System: Accuracy in
      Monitoring Hand Hygiene Compliance and Its Effect in Promoting Hand Hygiene
      Behaviour].
AB  - Hand hygiene is important in the prevention of healthcare-associated infection in
      hospitals, but the compliance rate of healthcare workers for hand hygiene is
      lower than expected. Hand hygiene compliance is usually monitored employing
      visual methods that are open to the Hawthorne effect and limited in terms of time
      and place. An automated monitoring system may provide the hand-hygiene compliance
      rate automatically and continuously, without suffering from the Hawthorne effect.
      An automated monitoring system may also improve hand hygiene by providing
      feedback data and real-time reminders. We report herein on an automated
      monitoring system that permits the tracking of hand hygiene opportunities and the
      disinfection compliance of healthcare workers. The aim is to establish the
      accuracy of the system in monitoring hand hygiene compliance and to estimate the
      effect of the system in promoting hand hygiene behaviour. Two studies were
      conducted. First, to evaluate the accuracy of hand hygiene compliance recorded by
      the automated monitoring system, we compared the hand hygiene compliance rate
      recorded by the automated monitoring system with that recorded by direct visual
      observation for 3 days during the same period in the same ward. For the overall
      period of simultaneous automated and human observations, the hand hygiene
      compliance rate was automatically observed to be 78% and visually observed to be
      75.4%. Second, to estimate the effect of the automated monitoring system in
      improving health workers' compliance with hand hygiene, we installed monitoring
      equipment in one ward and measured the compliance rate via the automated
      monitoring system for 13 weeks. This study included Phase 1 with a reminder only,
      Phase 2 with a reminder and feedback, and Phase 3 again with a reminder only. A
      significant increase in hand hygiene performance was observed during phase 2, and
      a high rate was sustained over phase 3. In phase 1, however, there was no
      increase in the hand hygiene compliance rate. We found the automated monitoring
      system to be a useful tool for not only monitoring hand hygiene but also for
      improving hand hygiene compliance.

PMID- 30277679
TI  - [A Case of Influenza A (H1N1) pdm09 Pneumonia Occurring Out of the Influenza
      Season].
AB  - A 42-year-old woman was referred to our hospital with a diagnosis of influenza A
      and pneumonia out of the influenza season. Chest CT findings resembled
      interstitial pneumonia, but we initiated anti viral agents and antibiotics.
      Flexible fiberoptic bronchoscopy was performed on hospital day 3. Based on the
      results of an RT-PCR analysis of broncho-alveolar lavage, this patient was
      diagnosed as having influenza viral pneumonia. In the influenza season, we can
      easily suspect influenza as a differential diagnosis, even if the patient's chest
      CT findings resemble interstitial pneumonia. Out of the influenza season,
      clinicians should take into consideration influenza viral pneumonia as a
      differential diagnosis.

PMID- 30277680
TI  - [The Effect of Intravenous Gamma-globulin Reagents on the Measurement Results of
      (1?3)-beta-D-glucan].
AB  - Serum (1->3) beta-D-glucan (BG) measurement is a useful test for systemic
      mycoses, and often used. On the other hand, various factors, including
      administration of intravenous immunoglobulins (IVIG) may cause false-positives.
      In the present study, we measured BG concentration of seven IVIG preparations
      with three lots respectively. BG levels varied with individual IVIG preparations
      (<3.0 - >300 pg/mL), and contamination from manufacturing processes was
      suspected.With serum BG concentration of clinical specimens obtained in Niigata
      University Medical & Dental Hospital, the difference between before and after
      administration of IVIG were calculated.The false-positive rate of BG due to IVIG
      administration was 9.8 %, and the positive predective value was reduced to 37.5%.
      Above all, administration of IVIG can complicate the BG test's interpretation,
      and caution is required.

PMID- 30277681
TI  - [Investigation of the Pathophysiology and Diagnostic Methods Through a Case of
      Acute HIV Infection in which the Western Blot Method Remained Negative Over the
      Long Term and the 4th Generation Screening Assay Became Negative for a Certain
      Period of Time after Initiating Antiretroviral Therapy].
AB  - : Confirmatory tests using Western blot (WB) and HIV-1 nucleic acid testing (HIV
      1 RNA) following a positive screening test are required for the diagnosis of HIV
      1 infection according to the current Japanese guidelines for HIV-1/2 diagnosis.
      We report herein on a rare case in a patient who remained negative for WB over 10
      months in spite of being positive by fourth-generation immunoassays (4thGIA) and
      who subsequently seroreverted by 4thGIA for three months after initiating
      antiretroviral therapy. Case: A man in his early twenties previously visited a
      hospital because of fever in October 2012. Laboratory data revealed
      leukocytopenia, thrombocytopenia and increased serum ferritin, suggesting
      hemophagocytic syndrome (HPS). During that visit, he tested positive for a
      4thGIA, but negative for HIV-1 WB and his result of HIV-1 RNA result was detected
      invalid because of the presence of some inhibitory material in his RNA
      preparation. Thereafter, he was diagnosed as having cytomegalovirus-associated
      HPS treatment was for which initiated. In January 2013, he developed Pneumocystis
      jirovecii pneumonia, and his HIV-1 RNA viral load was 7.7 * 105 copies/mL in
      February 2013. Acute HIV infection was suspected, because the HIV-1 WB remained
      negative. He was started on antiretroviral therapy in April 2013. His 4thGIA was
      converted to negative in May 2013 and was reconverted to positive in August 2013.
      HIV-1 WB, however, continued to be indeterminant until February 2014, in which it
      turned positive for the first time according to the CDC criteria. Methods and
      Results: The genetic analyses of HIV-1 were done on the gag, env, nef and pol
      region of the HIV-1 gene from the patient. There was no clear element to delay
      antibody production on the virus side. Preserved specimens of the patient were
      measured with eight kinds of HIV screening assay. It was thought that the fourth
      generation assay was positive only by the presence of the antigen until March
      2013 because the antibody had not been detected. Discussion: We encountered a
      case of acute HIV infection in which the WB result was negative for 10 months
      after the first positive response of the 4thGIA. The 4thGIA is essential for the
      early diagnosis and early treatment of HIV infection; therefore, the 4thGIA
      should be strictly recommended to avoid the use of older generations of
      immunoassay in the diagnostic guidelines. The role of the WB test should be
      examined closely from various aspects for use as a confirmatory test under recent
      laboratory situations in which highly sensitive and specific methods, e.g. the
      4th GIA, have become available. In addition, unnecessary confusion due to the
      diversities of antibody formation should be avoided. The antibody detection tests
      for HIV are still necessary and indispensable for the confirmation of the disease
      or the diagnosis of the acute infection stage. Therefore development of a newer
      antibody measuring method which could achieve an easier operation and should have
      a higher sensitivity and specificity for HIV confirmation is strongly expected.

PMID- 30277682
TI  - [The Deveroppment of Screening Methods Using the Disk Diffusion Method for
      Carbapenemase-producing Enterobacteriaceae].
AB  - Carbapenem-resistant Enterobacteriaceae (CRE) are increasing globally.
      Particularly, carbapenemase-producing Enterobacteriaceae (CPE) are of concern.
      Rapid and accurate detection of these strains is critical for appropriate
      antimicrobial use and hospital infection control. In the present study, criteria
      for CPE screening were examined using a carbapenem susceptibility disk.
      Carbapenemase producers showed minimal inhibition zones for faropenem (5 MUg): 6
      12 mm (mean: 6.9 mm). Some strains with the IMP-6 genotype showed inhibition
      zones of >30 mm for imipenem (10 MUg) and biapenem (10 MUg). All strains that
      formed inhibition zones for FRPM had the IMP-6 genotype. The cut off values of
      carbapenemase-producers, determined by ROC analysis, were 12 mm for FRPM, 24 mm
      for meropenem (10 MUg), 29 mm for BIPM, 25 mm for doripenem (10 MUg), 26 mm for
      IPM, and 24 mm for panipenem (10 MUg). Thus, the sensitivity was the highest
      (100%) for FRPM. Specificities were 93.44% for MEPM and DRPM and 85.25% for FRPM.
      Consequently, a drug sensitivity test using FRPM (5 MUg) disks facilitates simple
      and accurate CPE screening.

PMID- 30277683
TI  - [A Case of Multiple Venous Thromboses Associated with Acute Cytomegalovirus
      Infection].
AB  - A previously healthy 44-year-old male presented with fever, abdominal pain, liver
      dysfunction and lymphadenopathy. He was diagnosed as having acute cytomegalovirus
      (CMV) infection with elevated CMV-IgG and IgM, and observed with supportive
      therapy. He was admitted to our hospital with prolonged fever lasting for a
      month. Enhanced CT revealed multiple thromboses in the right pulmonary artery and
      superior mesenteric vein. Follow-up CT after one week revealed new-onset
      thromboses in the left pulmonary artery and common iliac vein. Screening tests
      for thrombophilia were negative. His symptoms were improved with anticoagulant
      therapy with intravenous heparin, followed by oral warfarin. He was discharged on
      admission day 28 with good condition. Follow-up CT after 6 months revealed
      complete resolution of the thromboses. Anticoagulant therapy was stopped after 9
      months, and he has been well without recurrence. Though vascular thrombosis is a
      rare complication, we must be alert to the signs and symptoms of thrombosis in
      patients with acute CMV infection.

PMID- 30277684
TI  - [Successful Treatment of Immune Reconstitution Inflammatory Syndrome with
      Corticosteroid for Patient with Kaposi's Sarcoma Extending into the Respiratory
      Tract and Both Lungs].
AB  - An HIV-infected man in his 30s was transferred to our hospital after the
      discontinuation of antiretroviral therapy (ART) for 4 years. An intraoral tumor
      was identified, and a biopsy was performed. The diagnosis was Kaposi's sarcoma
      (KS) and disseminated lesions were detected in his respiratory tract and both
      lungs on computed tomography (CT) and 2-[18F] fluoro-2-deoxy-D-glucose positron
      emission tomography (FDG/PET) imaging with increasing standardized uptake volume
      (SUV: max 7.4). On the 7th day, he was intubated to maintain his airway, then
      antiretroviral therapy and chemotherapy with pegylated liposomal doxorubicin were
      immediately initiated. After a period of remission, pulmonary lesions were
      detected again. We regarded them as a manifestation of immune reconstitution
      inflammatory syndrome (IRIS) and gave him short term corticosteroids. The lesions
      were then successfully controlled without additional chemotherapy. This case
      suggests that early induction of ART and intensive care can result in the
      survival of patients with KS having serious stenosis of the respiratory tract.
      Furthermore, this presenting case suggested that the use of corticosteroids could
      be a candidate to control IRIS even in patients with Kaposi's sarcoma.

PMID- 30277685
TI  - [Mycotic Aneurysm by Saccharomyces cerevisiae-accompanying Ascending Aortic Graft
      Infection: A Case Report].
AB  - We treated an extremely rare case of a mycotic aneurysm with infection of an
      artificial blood vessel by Saccharomyces cerevisiae, which was the first case in
      Japan. The patient was an 84-year-old woman. Five months before hospitalization,
      replacement of the ascending aorta was performed for a dissecting aneurysm of the
      ascending aorta. On regular follow-up examination, she had no symptoms, but
      accumulation of a liquid was detected around the artificial blood vessel on
      computed tomography (CT) imaging. She was immediately hospitalized. An emergency
      operation was performed because of the infected aneurysm, which accompanied
      infection of the artificial blood vessel. We could not detect any microorganisms
      in the blood or tissue culture, but we made a diagnosis of S. cerevisiae
      infection after performing broad-range polymerase chain reaction (PCR), followed
      by deoxyribonucleic acid (DNA) sequencing analysis.When an infected aneurysm is
      suspected after imaging analysis, such as CT, in a patient without fever or chest
      pain and with poor inflammatory reactions, an infected aneurysm caused by a
      fungus should be considered, even though blood or tissue culture results are
      negative. It is important to perform histopathological examination using Grocott
      silver stain and genetic testing (broad-range PCR and DNA sequencing analysis) of
      the tissue to identify the fungal infection.In the elderly, the number of cases
      of infection with S. cerevisiae may increase, and these cases may require more
      attention in the near future.

PMID- 30277686
TI  - [Medical Social Emergency Detected in Attendance by Valencia Samu].
AB  - Objectives: To analyze the social emergency caused by vulnerability situations or
      exclusion risk discovered through the health service SAMU in the city of
      Valencia. Method: To do it mixed methodology has been used. For the quantitative
      part 195 questionnaires were collected in the eight SAMU mobile units, all of
      them were completed during services, descriptive and inferential statistics were
      used. For qualitative part semi-structured interviews were performed to SAMU and
      SAUS professionals. Categories and qualitative matrix was analyzed with
      ATLAS.tiv7. Results: From a total of 195 emergencies, 35 (17.9%) were attended on
      Tuesday. December was the month in which most emergencies were presented 48
      (24.6%). 54.7% took place between 9 and 16 hours, of which 93 (47.7%) out of the
      SAUS working hours. From emergencies, 84 (50.5%) did not require transfer to
      hospital, compared to 83 (49.5%) than were required. SAMU units asked for social
      intervention in 27 (14%) cases, 24 (89%) required transfer to hospital. There was
      a significant (0.000), existing relationship between emergencies requiring
      hospital transfer by the SAMU and requiring social intervention. In interviews is
      demonstrated detection by the SAMU and intervention by the SAUS of social
      emergency. Of the qualitative results, we obtained that the SAMU across his
      sanitary emergencies detects social needs subject to valuation and intervention
      for SAUS. Conclusions: This study shows that SAMU of Valencia is a social
      emergency detector subject to social intervention in their daily work. The
      results support the proposal of a service that runs 24 hours seven days a week.

PMID- 30277695
TI  - [Promoting Intergenerational Relationships as a Strategy to Face the Challenges
      of Demographic Aging].
AB  - Nowadays, social and health representatives are putting the focus on emerging
      need: promote intergenerational programs and practices to generate spaces of
      encounter and collaboration between people of different ages. According to it,
      the purpose of intergenerational practices should be to achieve as aim for a
      society for all ages, regardless of age, an expression proposed by United
      Nations, not only to integrate all ages but to respond to their needs and provide
      them a higher quality of life.

PMID- 30277696
TI  - [Clinical Characteristics of Invasive Pneumococcal Disease of the Mucoid
      Phenotype: A Case Series].
AB  - Streptococcus pneumoniae is a gram-positive coccus that causes invasive and non
      invasive pneumococcal diseases. Invasive pneumococcal disease (IPD) is defined as
      an infection confirmed by the isolation of S. pneumoniae from a normally sterile
      site. IPD has a high mortality rate of around 20% in adults. Colonies of S.
      pneumoniae show various morphological features which include a mucoid appearance.
      The production of large amounts of capsular polysaccharide gives colonies of S.
      pneumoniae their mucoid appearance. This is thought to be a mechanism of
      microbial escape from phagocyte killing, leading to strong pathogenicity despite
      their high susceptibility to antibiotics. To our knowledge, the clinical
      characteristics of patients with mucoid IPD are unknown. We retrospectively
      analyzed the records of adult patients with IPD of the mucoid phenotype at Teine
      Keijinkai Hospital, Hokkaido, Japan, between 2009 and 2015.Seven patients (six
      males) with age range between 62 and 80 years were diagnosed as having mucoid IPD
      during the study period. Two patients had a history of malignancy and diabetes
      mellitus respectively, and six patients were living independently. No patients
      were previously vaccinated with pneumococcal vaccine. Six patients had clinical
      manifestations of pneumonia; one patient had multiple concomitant complications
      of mastoiditis, meningitis, and prosthetic joint infection. All isolates were
      isolated from blood. All isolates were susceptible to beta-lactam antibiotics,
      while six isolates were resistant to macrolides and chloramphenicol. Based on the
      Quellung reaction and real-time polymerase chain reaction (PCR) results, one
      isolate of mucoid phenotype was confirmed as serotype 3 with the penicillin
      binding protein gene of pbp2x and the macrolide resistant gene of ermB. Although
      all patients received appropriate antibiotics based on susceptibility testing,
      four patients required mechanical ventilation and vasopressors. One patient had
      neurological sequelae (hypacusis) and two patients died during the course of
      hospitalization. This case series suggests that mucoid IPD can occur in
      immunocompetent hosts and can cause high mortality. Since most of the mucoid
      phenotype of S. pneumoniae are serotype 3, widespread use of pneumococcal vaccine
      is important to prevent morbidity and mortality associated with IPD.

PMID- 30277697
TI  - [Bacteriological Properties of Meropenem-resistant Escherichia coli Isolated from
      Seven Patients within a Month].
AB  - From April to May 2014, a total of seven cases of meropenem (MEPM)-resistant
      Escherichia coli were isolated from the sputum specimens in 7 different patients
      in a community hospital.The MICs of MEPM for isolates were 8 to 32 MUg/mL,
      whereas the MICs of imipenem (IPM) were 0.5 MUg/mL or 1 MUg/mL. All of the
      isolates possessed the metallo beta-lactamase (MBL) IMP-6 gene, and were CTX-M-2
      type extended-spectrum beta-lactamase (ESBL)-producers. Pulsed-field gel
      electrophoresis (PFGE) patterns for the isolates were identical.At the time of
      specimen collection, one patient had been hospitalized for a long time and the
      other six patients had been comparatively recently admitted to the hospital. Of
      the six patients, two had been staying in the same nursing facility before
      admission, whereas the remaining 4 patients had no relationship with each other
      because they had been in separate locations. Thus, these cases were not
      considered to be nosocomially-acquired infection.Our findings suggest that MBL
      producing E. coli has been spreading widely in the community such as in local
      nursing facilities.

PMID- 30277698
TI  - [Bacteriological Analysis of Pneumococcus Detected from the Sputum of
      Hospitalized Children].
AB  - 7-valent pneumococcal conjugate vaccine (PCV7) has been included in the routine
      immunization schedule since April 2013 in Japan. Serotype replacement - a
      phenomenon by which serotypes are replaced by non-vaccine serotypes after vaccine
      introduction - has been reported in invasive pneumococcal disease (IPD).
      Pneumococcus in sputum samples is one of the major causes of bronchopulmonary
      infection in children.We tried to verify whether serotype replacement of
      Pneumococcus occurs in sputum samples in a similar manner as in IPD.From August
      2014 to September 2015, we performed antimicrobial susceptibility testing and
      serotyping of Streptococcus pneumoniae from sputum samples and investigated the
      history of PCV from hospitalized children with S. pneumoniae bronchopulmonary
      infection.From the results of our investigation, 80.3% of children have received
      PCV at least once. Serotypes of Pneumococcus were determined in 92.4% of tested
      strains and PCV13 strains accounted for only 9.8%. Major isolated serotypes were
      15A (21.3%), 35B (19.7%), and 6C (13.1%). Those were not included in PCV13, i.e.
      serotype replacement occurs in bronchopulmonary infection just as in IPD. The
      results of antimicrobial susceptibility testing for Penicillin G indicated that
      penicillin-resistant S. pneumoniae (PRSP) accounted for 4.5%, penicillin
      intermediate resistant S. pneumoniae (PISP) accounted for 47.0% and penicillin
      susceptible S. pneumoniae (PSSP) accounted for 48.5%. When examining the drug
      susceptibility by serotypes, 15A, 19A, 23A and 35B showed a high percentage of
      non-susceptibility. This means there is a difference in the resistant trend by
      serotypes.In our study, it became clear that verifying of the serotypes of
      Pneumococcus in sputum is meaningful and surveillance of serotypes is important
      for evaluation of vaccination as IPD.

PMID- 30277699
TI  - [Evaluation of a Newly Developed Campylobacter Antigen Detection Kit for Patients
      with Enteritis].
AB  - The newly developed rapid diagnostic test (RDT, DK14-CA1, Denka Seiken Co., Ltd.)
      to detect Campylobacter antigen was evaluated using fecal specimens of patients
      with enteritis. The RDT is an immunochromatographic assay using colored latex and
      can detect Campylobacter antigen (C. jejuni and C. coli) from patients' stool
      samples within 15 minutes.A total of 227 stool samples obtained from patients
      with enteritis were examined and the results were compared with conventional
      culture methods. Overall sensitivity, specificity, accuracy and positive
      predictive value (PPV) were 75.6%, 98.6%, 89.9% and 97.0% respectively. Among 53
      severe cases defined with their clinical findings, sensitivity, specificity,
      accuracy and PPV were 82.1%, 100%, 90.6% and 100% respectively. Mean time to
      obtain the result with the RDT was 7 minutes whereas the culture method took 2.2
      days.This study revealed the usefulness of the newly developed RDT as a rapid
      detection tool for Campylobacter antigen. Although the RDT has a little lower
      sensitivity compared with culture method, the simple and rapid test can
      contribute to treatment decisions for patients with enteritis and can be used at
      the patient's bedside and in outpatient clinics.

PMID- 30277700
TI  - [Bacteremia Due to Bacillus subtilis: A Case Report and Clinical Evaluation of 10
      Cases].
AB  - A 59-year-old male presented with fever, and was admitted for bacteremia due to
      gram-positive rod. All 5 sets of blood cultures obtained prior to the initiation
      of vancomycin tested positive for Bacillus subtilis. Based on the susceptibility
      test result, the antibiotics were changed to levofloxacin to complete a total of
      fourteen days treatment. The patient recovered without relapse over one year.
      Despite thorough examinations, the portal of entry of B. subtilis remained
      unclear.We retrospectively reviewed ten cases of bacteremia due to B. subtilis
      over 5 years in our hospital. The cases with positive B. subtilis blood cultures
      which were evaluated as contamination were excluded from the review. The most
      common portal of entry of B. subtilis was secondary bacteremia due to perforation
      or ileus (70%), followed by an unknown site (30%). B. subtilis should be
      considered not only as a contaminant but also as a true pathogen of bacteremia.

PMID- 30277701
TI  - [Influence of Conveen(r) Optima in the Life of a Male with Incontinence].
AB  - Urinary incontinence is one of the most influential factors which negatively
      affect patients' quality of life suffering from spinal cord injury. It affects
      their self-esteem, interpersonal and work relations, their independence, together
      with their leisure and free time activities. Urine collectors are among the
      products that contribute to improve the autonomy and quality of life of patients
      with urinary incontinence. A simple functioning device which can be determinant
      in achieving that urinary incontinence has an almost nil impact in the life of a
      patient with spinal cord injury. Choosing the right product is the key to success
      and the reason why we introduce Conveen(r) Optima, analyzing the manifold factors
      directly or indirectly related to the use of this collector.

PMID- 30277702
TI  - [Pneumonia and Streptococcal Toxic Shock Syndrome Due to Group A Streptococci: A
      Case Report].
AB  - A 71-year-old woman who was undergoing immunosuppressive therapy presented with a
      7-day history of productive cough and 2-day history of fever. She was diagnosed
      with severe pneumonia and septic shock. Meropenem, azithromycin, large amounts of
      fluids, and noradrenaline were administered, and high-flow nasal cannula oxygen
      therapy was provided. The gross appearance of the aspirated sputum was ginger
      like, and the gram-positive cocci in chains were identified as group A beta
      hemolytic streptococci (GAS), Streptococcus pyogenes. The blood sample culture
      test revealed negative results. Based on Stevens' criteria, the patient was
      finally diagnosed as having streptococcal toxic shock syndrome (STSS).
      Antibiotics were switched to ampicillin/sulbactam and clindamycin as an antitoxin
      treatment, and the patient was discharged on day 33. Serotypes of GAS were T1,
      M1, and emm1. Superantigens spe A, spe B, and spe F were present, and spe C was
      absent. These observations were compatible with the clinical features of
      hypotension. GAS is an uncommon cause of community-acquired pneumonia, which when
      potentially complicated with STSS can lead to a high mortality rate, and the
      rapid progression is particularly a striking feature. We should be aware that GAS
      can cause pneumonia, and antitoxin treatment can play a key role in STSS
      management.

PMID- 30277703
TI  - [Valacyclovir Maintenance Therapy for a Case of Unilateral Acute Retinal Necrosis
      during Chemotherapy].
AB  - Acute retinal necrosis (ARN) is an infectious retinitis caused by varicella
      zoster virus (VZV), herpes simplex or cytomegalovirus. Without systemic therapy,
      ARN may progress bilaterally in seventy percent of unilateral patients. A 38-year
      old-man was admitted to our hospital with Hodgkin's lymphoma and hemophagocytic
      lymphohistiocytosis. During the chemotherapy, left facial herpes zoster
      developed. He received valacyclovir for 14 days. After improvement of the
      blisters, he continued acyclovir as secondary prophylaxis. Three weeks after the
      facial zoster, sudden visual loss in the left eye occurred. ARN induced by VZV
      was diagnosed with ophthalmoscopy and the polymerase chain reaction test of the
      anterior chamber. Because continuous chemotherapy for Hodgkin's lymphoma was
      needed, he continued valacyclovir as secondary prophylaxis for 6 months and he
      accomplished the chemotherapy without contralateral progression. Our case
      suggested the utility of valacyclovir for secondary prophylaxis. Further
      experiments would be required to establish secondary prophylaxis in
      immunocompromised patients.

PMID- 30277704
TI  - [A Case of Vibrio vulnificus Infection Improved with Conservative Treatment in
      Kagoshima].
AB  - We herein report on a case of Vibrio vulnificus infection that was improved by
      conservative treatment in Kagoshima, Japan. A 75-year-old Japanese woman with
      liver cirrhosis presented to our hospital with shaking chill and right lower leg
      pain. Her blood culture was positive for V. vulnificus, and bullae had newly
      appeared on the right leg. Further history taking revealed that she had eaten
      some raw seafood before admission. She recovered following administration of
      antibiotics and small incisions in the lesion. West Japan (especially, the
      northern parts of Kyushu island) is well known as an endemic area of V.
      vulnificus infection: however, some cases had been reported in other areas in
      Japan. When clinicians treat cellulitis with risk factors, we should consider the
      possibility of V. vulnificus infection, even in a non-endemic area. Taking blood
      culture and early administration of appropriate antibiotics may contribute to
      conservative cure of some case of V. vulnificus infection.

PMID- 30277705
TI  - [Implementing Telemedicine, EHealth and Telephonic Nursing Assistance in Spain].
AB  - Introduction: Tele-Health or eHealth are defined as diversified health services
      provided remotely by a team of professionals using ICT (Information and
      Communication Technology) to improve the health of a user or population.
      Development: The development of ICT during the 2000 and 2010 decades allowed for
      a wider applicability of these services. Techniques like teleradiology and
      telepathology appeared. Tele-nursing began to be practiced through
      teleconsultations. Tele-nursing emerged from consulting telephone nurses in the
      United Kingdom and Canada. In 2005, the WHO established the Global eHealth
      Observatory to review the benefits of ICT. Currently in Spain, 061 Cat Salut
      Respon, managed by nurses, gives coverage to Catalonia through its website,
      telephone, email or chat. In Andalusia, Salud Responde is a service and
      information center providing citizens with remote healthcare. Conclusions: Health
      systems offer services through multichannel schemes and specific applications
      (apps) improving accessibility anytime, anywhere, provided with internet
      connection. The involvement of nurses in eHealth programs, such as telenurses, is
      increasingly spreading in Spain, mirroring the trend at an international level.

PMID- 30277706
TI  - [Construction of an Instrument of Risk Assessment and Injury Severity for the
      Diaper Area in Infants: RDIC-lac].
AB  - Objective: To design an instrument to measure impairment of skin integrity in the
      diaper area of infants and severity of injury for the prevention and management
      of irritative diaper dermatitis. Methodology: Design in 3 phases: 1)
      comprehensive review and critical appraisal of literature to design the
      preliminary content of the instrument; 2) critical evaluation of initial proposal
      by an expert group (nursing and pediatric medicine) with opinion survey and ad
      hoc questions; 3) content analysis using data tabulation for the modification and
      final design of the instrument. Setting: Primary Care Management of Tenerife.
      Results: In the 1st phase a proposed instrument is designed: two groups of risk
      factors (10 modulators risk and 9 high risk); and a severity scale with 5 aspects
      to assess including 4-5 items each (depth, location, extension, type of injury,
      signs of infection). The 2nd phase involved 19 professionals. A Tabulation of the
      data grouped into add or omit factors was used. The 3rd phase ends with a
      modified version of the instrument: 10 modulating factors, 5 of hig risk and 4
      items for each aspect to assess severity. Discussion-Conclusions: The scarce
      bibliography found and absence of similar tools explain the design. The next
      phase will be the validation of RDIC-lac instrument. Clinical Relevance:
      Susceptibility to prevent skin lesions in the diaper area in the pediatric age.

PMID- 30277707
TI  - Growing body of evidence supports intrauterine insemination as first line
      treatment and rejects unfounded concerns about its efficacy, risks and cost
      effectiveness.
AB  - IUI has been practiced for five decades but only three unconvincing trials
      attempted to demonstrate the superiority of IUI over sexual intercourse (SI). In
      the absence of evidence of its effectiveness, the National Institute for Clinical
      Excellence (NICE) recommended IVF over IUI after 2 years of unprotected SI. High
      quality recent data in well-constructed studies suggest that biases against IUI
      procedures and in favour of IVF are invalid. It is unethical to continue to
      misinform patients and stakeholders. The well-constructed randomised controlled
      trials (RCT) show IUI procedure to be efficient, with minimal risk, and above all
      improved cost-effectiveness when compared to IVF for live birth. IUI as first
      line treatment should be offered to most patients, while funding agencies and
      stakeholders need to be urgently informed of the cost-benefit in offering IUI.
      Fertility clinics, IVF interest groups, and regulatory bodies should amend their
      patient information and guidance to state that IUI should be the first line
      treatment and that IVF should be offered only when essential. Reappraising and
      promoting IUI based on evidence enhances patient autonomy, choices, and trust,
      while allowing the fertility industry to operate within an ethical and acceptable
      framework not seen as exploitative toward vulnerable patients.

PMID- 30277724
TI  - Ambulatory Blood Pressure Important for Decision-Making About Treatment.

PMID- 30277709
TI  - [Cross-Cultural Adaptaton and Validation of the Attitudes Towards Men in Nursing
      Scale (ATMINS)].
AB  - Introduction: Aiming at detecting possible causes for the lack of male nursing
      professionals, Bartfay et al. developed a questionnaire named Attitudes Towards
      Men in Nursing Scale (ATMINS), which they tested a university in Ontario, Canada.
      Objective: Achieve a cross-cultural adaptation and validation of the Attitudes
      Towards Men in Nursing Scale (ATMINS), in order to evaluate if results achieved
      using a Spanish sample are comparable with the Canadian study's results.
      Participantsm, Materials, and Method: Participants were recruited in universities
      of Alicante and Donostia (Basque Country). To assure voluntary participation in
      the study, all candidates were informed about the objective of the study and
      giving enough time to read the questionnaire. The questionnaire used was the
      Attitudes Toward Men in Nursing Scale (ATMINS), translated to Spanish. The
      Spanish version of the ARMINS scale was handed over to a total of 142 students
      from the Nursing Universities of Alicante and Donostia. Time needed to fill the
      questionnaires didn't exceed 5 minutes in any case, and no difficulty was
      observed during implementation. After testing the scale, an internal consistency
      analysis was performed using Cronbach's Alpha with correction by eliminating
      items. Validation of construct was done via Exploratory Factorial analysis with
      Varimax rotation. Results: The results show a reliability which does not reach a
      moderate degree. Eliminating item 6 in all subsamples, as well as the total
      sample suppressing any of the other 5 items, increases internal consistency. The
      exploratory factorial analysis supports a bi-factorial structure of the
      questionnaire with very high saturation on each factor and a negative charge
      inside factor 2 for item 6. The negative charge of item 6 keeps the saturation
      (0.717) after its inversion. By performing an internal consistency analysis
      taking only into account items of factor 1, the scale's consistency improves with
      results close to 0.70. Conclusion: The revised scale is a tool which enables easy
      and fast application. It is valid for the Spanish sample and provides an
      acceptable internal consistency. The results obtained in both universities in
      Spain and in Canada are comparable.

PMID- 30277708
TI  - [Influence of Family in the Patient with Neurological Pathology and Acute
      Confusional Syndrome].
AB  - Summary: Given the type of pathology and age of patients in the inpatient unit of
      Neurology, Hospital de Cabuenes (Gijon), acute confusional syndrome (ACS) is very
      common in this service. Objective: To determine the influence of the family,
      within the limits of the hospital, in patients with neurological disease
      suffering from SCA. Methodology: A prospective, observational, descriptive study
      of 53 patients with neurological disease that suffered from SCA was performed.
      The study variables were: disorientation, agitation, medication, effectiveness,
      and body grip on each shift with and without family. All those patients suffering
      from any dementia or psychiatric problem before entering were discarded. Results:
      The mean age of the patients was 83 years old. The most common pathology was
      ICTUS. The patients with family were 47.4% versus 52.6% without family in three
      shifts. 70.3% of the patients became disoriented with family; for patients
      without family the percentage increased up to 83.8%. As far as nervousness is
      concerned, 11.4% of the patients with family experienced this behaviour in the
      three shifts; no-family patients suffering from nervousness were 29.4%.
      Medication was administered to 33% of the patients with family, and to 44% of no
      family patients. The effectiveness was 66.5% for patients with family and 48% for
      no-family patients. The use of body grip in the three shifts was 7.6% for
      patients with family and 64.5% for no-family patients. Conclusions: Family has a
      beneficial effect on neurological patients with ACS, specially by reducing the
      use of mechanical restraint, helping to preserve the dignity of elderly patients
      in an adverse environment such as a hospital.

PMID- 30277725
TI  - Cannabinoids Somewhat Helpful for Nausea, Maybe Helpful for Spasticity, Probably
      Not Helpful for Nonneuropathic Pain.

PMID- 30277726
TI  - Influenza Vaccination Recommendations for 2018-2019: Updates from ACIP.

PMID- 30277727
TI  - Cerumen Impaction: Diagnosis and Management.
AB  - Cerumen production is a normal and protective process for the ear canal. However,
      cerumen should be removed when it causes symptoms (e.g., hearing loss, itching,
      pain, tinnitus) or prevents assessment of the external auditory canal, the
      tympanic membrane, or audiovestibular system. Cerumen should also be removed when
      it limits examination in patients who cannot communicate their symptoms, such as
      those with dementia or developmental delay, nonverbal patients with behavioral
      changes, and young children with fever, speech delay, or parental concerns.
      Patients with coagulopathies, hepatic failure, thrombocytopenia, or hemophilia,
      and those taking antiplatelet or anticoagulant medications, should be counseled
      about the increased risk of bleeding in the external auditory canal when cerumen
      is removed. Effective treatment options include cerumenolytic agents, irrigation
      with or without cerumenolytic pretreatment, and manual removal. Home irrigation
      with a bulb syringe may be appropriate for selected adults. Cotton-tipped swabs,
      ear candling, and olive oil drops or sprays should be avoided. If multiple
      attempts to remove the impacted cerumen-including a combination of treatments-are
      ineffective, clinicians should refer the patient to an otolaryngologist.
      Persistent symptoms despite resolution of the impaction should also prompt
      further evaluation for an alternative diagnosis.

PMID- 30277728
TI  - Depression: Screening and Diagnosis.
AB  - Depression affects an estimated 8% of persons in the United States and accounts
      for more than $210 billion in health care costs annually. The U.S. Preventive
      Services Task Force (USPSTF) and American Academy of Family Physicians recommend
      screening for depression in the general adult population. Additionally, the
      USPSTF recommends screening children and adolescents 12 to 18 years of age for
      major depressive disorder. All screening should be implemented with adequate
      systems in place to ensure accurate diagnosis, effective treatment, and
      appropriate follow-up. The two-item and nine-item Patient Health Questionnaires
      (PHQs) are commonly used validated screening tools. The PHQ-2 has sensitivity
      comparable with the PHQ-9 in most populations; however, the specificity of the
      PHQ-9 ranges from 91% to 94%, compared with 78% to 92% for the PHQ-2. If the PHQ
      2 is positive for depression, the PHQ-9 or a clinical interview should be
      administered. Screening all postpartum women for depression is recommended by the
      USPSTF, American Academy of Family Physicians, American Academy of Pediatrics,
      and American College of Obstetricians and Gynecologists. Women should be screened
      for depression at least once during the perinatal period using the PHQ-2, PHQ-9,
      or Edinburgh Postnatal Depression Scale. In older adults, the Geriatric
      Depression Scale is also an appropriate screening tool for depression. If
      screening is positive for possible depression, the diagnosis should be confirmed
      using Diagnostic and Statistical Manual of Mental Disorders, 5th ed., criteria.

PMID- 30277729
TI  - High Blood Pressure in Children and Adolescents.
AB  - High blood pressure in children and adolescents is a growing health problem that
      is often overlooked. Children should be screened for elevated blood pressure
      annually beginning at three years of age or at every visit if risk factors are
      present. In children younger than 13 years, elevated blood pressure is defined as
      blood pressure in the 90th percentile or higher for age, height, and sex, and
      hypertension is defined as blood pressure in the 95th percentile or higher. In
      adolescents 13 years and older, elevated blood pressure is defined as blood
      pressure of 120 to 129 mm Hg systolic and less than 80 mm Hg diastolic, and
      hypertension is defined as blood pressure of 130/80 mm Hg or higher. Ambulatory
      blood pressure monitoring should be performed to confirm hypertension in children
      and adolescents. Primary hypertension is now the most common cause of
      hypertension in children and adolescents. A history and physical examination and
      targeted screening tests should be done to evaluate for underlying medical
      disorders, and children and adolescents with hypertension should be screened for
      comorbid cardiovascular diseases, including diabetes mellitus and hyperlipidemia.
      Hypertension in children is initially treated with lifestyle changes such as
      weight loss if overweight or obese, a healthy diet, and regular exercise.
      Children with symptomatic hypertension (e.g., headaches, cognitive changes),
      stage 2 hypertension without a modifiable factor such as obesity, evidence of
      left ventricular hypertrophy on echocardiography, any stage of hypertension
      associated with chronic kidney disease or diabetes, or persistent hypertension
      despite a trial of lifestyle modifications require antihypertensive medications
      and should be evaluated for cardiovascular damage with echocardiography.
      Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium
      channel blockers, and thiazide diuretics are effective, safe, and well-tolerated
      in children.

PMID- 30277730
TI  - Morning vs. Evening Administration of Levothyroxine.

PMID- 30277731
TI  - Long-Acting Muscarinic Antagonists plus Inhaled Steroids is Equal to Long-Acting
      Beta-Agonists Plus Inhaled Steroids.

PMID- 30277733
TI  - Screening for Prostate Cancer: Recommendation Statement.

PMID- 30277734
TI  - Counseling Patients About Prostate Cancer Screening.

PMID- 30277735
TI  - Recombinant Zoster Vaccine (Shingrix) for the Prevention of Shingles.

PMID- 30277736
TI  - Screening for Prostate Cancer.

PMID- 30277737
TI  - Newborn with a Hyperextended Knee.

PMID- 30277738
TI  - Five-Day Nitrofurantoin Superior to Single-Dose Fosfomycin for Women with
      Uncomplicated UTI.

PMID- 30277739
TI  - Urinary Retention in Adults: Evaluation and Initial Management.
AB  - Urinary retention is the acute or chronic inability to voluntarily pass an
      adequate amount of urine. The condition predominantly affects men. The most
      common causes are obstructive in nature, with benign prostatic hyperplasia
      accounting for 53% of cases. Infectious, inflammatory, iatrogenic, and neurologic
      causes can also affect urinary retention. Initial evaluation should involve a
      detailed history that includes information about current prescription medications
      and use of over-the-counter medications and herbal supplements. A focused
      physical examination with neurologic evaluation should be performed, and
      diagnostic testing should include measurement of postvoid residual (PVR) volume
      of urine. There is no consensus regarding a PVR-based definition for acute
      urinary retention; the American Urological Association recommends that chronic
      urinary retention be defined as PVR volume greater than 300 mL measured on two
      separate occasions and persisting for at least six months. Initial management of
      urinary retention involves assessment of urethral patency with prompt and
      complete bladder decompression by catheterization. Suprapubic catheters improve
      patient comfort and decrease bacteriuria and the need for recatheterization in
      the short term; silver alloy-coated and antibiotic-impregnated catheters offer
      clinically insignificant or no benefit. Further management is decided by
      determining the cause and chronicity of the urinary retention and can include
      initiation of alpha blockers with voiding trials. Patients with urinary retention
      related to an underlying neurologic cause should be monitored in conjunction with
      neurology and urology subspecialists.

PMID- 30277740
TI  - Genetic Factors Should Be Considered When Caring for Colorectal Cancer Survivors.

PMID- 30277741
TI  - The Presence of Bull's Eye Lesion Is Not Required to Diagnose Lyme Disease.

PMID- 30277742
TI  - Matrix-Incorporated Polydopamine Layer as a Simple, Efficient, and Universal
      Coating for Laser Desorption/Ionization Time-of-Flight Mass Spectrometric
      Analysis.
AB  - Self-oxidative copolymerization of dopamine with alpha-cyano-4-hydroxycinnamic
      acid (CHCA) provides an efficient and multifunctional platform for laser
      desorption/ionization time-of-flight mass spectrometry (LDI-TOF-MS) analysis. The
      polydopamine coating layer embedded with the CHCA matrix can be readily formed on
      nanomaterials and solid substrates without additional surface treatments to
      generate an efficient LDI-TOF-MS platform for the analysis of small molecules as
      well as synthetic polymers. This coating can be further functionalized with
      specific ligands for target enrichment from complex biological media, providing
      analyte capture for subsequent LDI-TOF-MS analysis.

PMID- 30277743
TI  - Microporous Zeolite@Vertically Aligned Mg-Al Layered Double Hydroxide Core@Shell
      Structures with Improved Hydrophobicity and Toluene Adsorption Capacity under Wet
      Conditions.
AB  - Zeolites have been recognized as one type of the most promising adsorbents for
      capturing volatile organic compounds (VOCs, e.g., toluene), but their performance
      suffers severely from water vapor under wet conditions. In this contribution, we
      demonstrated that the hydrophobicity of microporous zeolites can be significantly
      improved by coating vertically aligned LDH nanoplatelets when the contact angle
      is increased from 16.5-20.1 degrees  to 44.4-64.2 degrees . The toluene
      adsorption capacity of such synthesized zeolite@LDH core@shell composites in wet
      conditions can thus be largely enhanced when the breakthrough time is increased
      from 6.4-10.8 to 20.1-27.5 min.

PMID- 30277744
TI  - Light-Scattering Sizing of Single Submicron Particles by High-Sensitivity Flow
      Cytometry.
AB  - Rapid and reliable size measurement of single submicron particles (100-1000 nm)
      is important for quality control of particulate matter, biomedical research,
      environmental study, and drug delivery system development. Though direct
      measurement of the elastically scattered light from individual submicron
      particles represents the simplest method for particle size measurement, the
      inadequate instrument sensitivity and complicated relationship between scattering
      intensity and particle size render it a great challenge. Combining the superior
      sensitivity of a laboratory-built high-sensitivity flow cytometer (HSFCM) in the
      side scattering (SSC) detection of single nanoparticles and the great efforts in
      synthesizing 38 highly monodisperse silica spheres ranging from 180 to 880 nm
      with small size intervals, here we report the first comprehensive comparison
      between the experimentally measured and Mie theory calculated intensities of
      light scattered by single submicron particles. Good agreements were observed for
      both the silica spheres and polystyrene beads at both the perpendicular and the
      parallel polarizations of the incident laser beam. Compared with perpendicular
      polarization, parallel polarization can resolve differently sized beads better
      due to the continuously increased scattering intensity with particle size. The
      predictive capability of the simple numerical model constructed in present work
      can be exploited to allow us to foresee scattering behavior on flow cytometers.
      More importantly, the linear correlation between the measured and the calculated
      scattering intensities enables us to develop a method that can measure the
      particle size of submicron particles with the precision and accuracy of Mie
      theory rather than a calibration curve fitted by several sparsely separated size
      reference standards. Comparable sizing resolution and accuracy to those of
      electron microscopy were demonstrated for Gram-positive bacteria Staphylococcus
      aureus. The as-developed method shows great potential in guiding the accurate
      size measurement of submicron particles.

PMID- 30277745
TI  - Piezo-phototronic Effect Enhanced Photodetector Based on CH3NH3PbI3 Single
      Crystals.
AB  - Piezoelectric organic-inorganic lead halide perovskites have recently attracted
      much attention in the field of optoelectronic devices. However, their
      piezoelectric properties as a possible way to modulate device performances have
      rarely been reported. Here, we study experimentally a photodetector based on
      CH3NH3PbI3(MAPbI3) single crystals, whose performance is effectively modulated
      via an emerging effect-the piezo-phototronic effect, which is to use the
      piezoelectric polarization charges to tune the optoelectronic processes at the
      interface. A piezoelectric coefficient of 10.81 pm/V of the CH3NH3PbI3 single
      crystal is obtained. Under 680 nm laser illumination with a power density of
      3.641 mW/cm2 and at an external bias of 2 V, compared to the case without
      straining, the light current of the photodetector is enhanced by ~120% when a
      43.48 kPa compressive pressure is applied. The response speed of the photocurrent
      is 3 and 2 times faster than the cases without applying pressure for the light-on
      and light-off states, respectively. This work proves that the performance of the
      photodetector based on MAPbI3 single crystals can be effectively enhanced by the
      piezo-phototronic effect, providing a good method for optimizing the performance
      of future perovskite-based optoelectronic devices.

PMID- 30277746
TI  - Substrate Profile of the Phosphotriesterase Homology Protein from Escherichia
      coli.
AB  - The phosphotriesterase homology protein (PHP) from Escherichia coli is a member
      of a family of proteins that is related to phosphotriestrase (PTE), a bacterial
      enzyme from cog1735 with unusual substrate specificity toward the hydrolysis of
      synthetic organic phosphates and phosphonates. PHP was cloned, purified to
      homogeneity, and functionally characterized. The three-dimensional structure of
      PHP was determined at a resolution of 1.84 A with zinc and phosphate in the
      active site. The protein folds as a distorted (beta/alpha)8-barrel and possesses
      a binuclear metal center in the active site. The catalytic function and substrate
      profile of PHP were investigated using a structure-guided approach that combined
      bioinformatics, computational docking, organic synthesis, and steady-state enzyme
      kinetics. PHP was found to catalyze the hydrolysis of phosphorylated glyceryl
      acetates. The best substrate was 1,2-diacetyl glycerol-3-phosphate with a kcat/
      Km of 4.9 * 103 M-1 s-1. The presence of a phosphate group in the substrate was
      essential for enzymatic hydrolysis by the enzyme. It was surprising, however, to
      find that PHP was unable to hydrolyze any of the lactones tested as potential
      substrates, unlike most of the other enzymes from cog1735.

PMID- 30277747
TI  - Targeting Tumor Microenvironment by Bioreduction-Activated Nanoparticles for
      Light-Triggered Virotherapy.
AB  - Solid tumors characteristically display higher levels of lactate production due
      to anaerobic metabolism of glucose. Meanwhile, the U.S. Food and Drug
      Administration (FDA) has approved virotherapy for use in cancer treatment;
      however systemic administration remains as a particular challenge. Here we report
      exploitation of tumor lactate production in designing a hypoxia-responsive
      carrier, self-assembled from hyaluronic acid (HA) conjugated with 6-(2
      nitroimidazole)hexylamine, for localized release of recombinant adeno-associated
      virus serotype 2 (AAV2). The carrier is loaded with lactate oxidase (LOX) and is
      permeable to small molecules such as the lactate that accumulates in the tumor.
      Subsequently, LOX oxidizes the lactate to pyruvate inside the carrier,
      accompanied by internal lowering of oxygen partial pressure. Bioreduction of the
      2-nitroimidazole of the HA conjugated with 6-(2-nitroimidazole)hexylamine
      converts it into a hydrophilic moiety and electrostatically dissociates the
      carrier and virus. Efficacious and specific delivery was proven by transduction
      of a photosensitive protein (KillerRed), enabling significant limitation in tumor
      growth in vivo with photodynamic therapy. An approximate 2.44-fold reduction in
      tumor weight was achieved after a 2-week course, compared with control groups.
      Furthermore, conjugation of the AAV2 with iron oxide nanoparticles ("magnetized"
      AAV2) facilitated magnetic resonance imaging tracking of the virus in vivo. Taken
      together, the solid tumor microenvironment promotes bioreduction of the lactate
      responsive carrier, providing rapid and specific delivery of AAV2 for light
      triggered virotherapy via systemic administration.

PMID- 30277748
TI  - Method for the Detailed Characterization of Cosputtered Inorganic Luminescent
      Material Libraries.
AB  - Understanding the behavior of combinatorially developed luminescent materials
      requires detailed characterization methods that have been lacking thus far. We
      developed a device for directly surveying the luminescent properties of thin-film
      libraries created through combinatorial gradient sputter deposition. Step-scan
      recorded excitation-, emission- and luminescence decay spectra of a thin-film
      library were resolved and combined with EDX measurements on the same film,
      relating composition to luminescent properties. This technique was applied to a
      single-substrate gradient thin-film library of NaBr0.73I0.27 to NaBr0.09I0.91,
      doped with 6.5% to 16.5% Eu2+. This gradient film closely followed Vegard's law,
      with emission fluently shifting from 428 to 439 nm. In comparison, pure NaBr:Eu2+
      showed emission at 428 nm and NaI:Eu2+ at 441 nm. Luminescence decay measurements
      demonstrated a great degree of concentration quenching in the gradient film. From
      these measurements we could conclude that an optimized phosphor would most
      efficiently luminesce when close to NaI:Eu2+. This gradient film confirmed that
      the method presented in this work allows to both study and optimize luminescent
      behavior in a broad range of host- and dopant systems.

PMID- 30277749
TI  - A Highly Bioactive Lys-Deficient IFN Leads to a Site-Specific Di-PEGylated IFN
      with Equivalent Bioactivity to That of Unmodified IFN-alpha2b.
AB  - Although conjugation with polyethylene glycol (PEGylation) improves the
      pharmacokinetics of therapeutic proteins, it drastically decreases their
      bioactivity. Site-specific PEGylation counters the reduction in bioactivity, but
      developing PEGylated proteins with equivalent bioactivity to that of their
      unmodified counterparts remains challenging. This study aimed to generate
      PEGylated proteins with equivalent bioactivity to that of unmodified
      counterparts. Using interferon (IFN) as a model protein, a highly bioactive Lys
      deficient protein variant generated using our unique directed evolution methods
      enables the design of a site-specific di-PEGylated protein. Antiviral activity of
      our di-PEGylated IFN was similar to that of unmodified IFN-alpha2b. The di
      PEGylated IFN exhibited 3.0-fold greater antiviral activity than that of a
      commercial PEGylated IFN. Moreover, our di-PEGylated IFN showed higher in vitro
      and in vivo stability than those of unmodified IFN-alpha2b. Hence, we propose
      that highly bioactive Lys-deficient proteins solve the limitation of conventional
      PEGylation with respect to the reduction in bioactivity of PEGylated proteins.

PMID- 30277750
TI  - Combinatorial Thin Film Sputtering Au xAl1- x Alloys: Correlating Composition and
      Structure with Optical Properties.
AB  - The Au-Al alloy system was investigated via a combinatorial thin film sputtering
      method for its potential as a plasmonic material. Au xAl1- x combinatorial
      libraries were cosputtered from Au and Al elemental targets and the composition,
      phase, and dielectric function of a ~350 nm film was determined using energy
      dispersive spectroscopy (EDS), grazing incidence X-ray diffraction (GIXRD), and
      spectroscopic ellipsometry, respectively. The phase evolution and optical
      properties were analyzed after annealing various compositions under a vacuum. The
      phases present matched the expected phases based on the published Al-Au binary
      phase diagram at all compositions. Interestingly, the mixed phase Al-AuAl2 region
      showed the most optical tunability, where a maximum in the real part of the
      dielectric function progressively shifted to higher energy for increasing gold
      concentration. For almost pure AuAl2, the imaginary component is largely reduced
      in the visible range and is comparable to that of pure Al in the UV region. A 20
      nm-thick film with composition Au0.74Al0.26 was studied using a (scanning)
      transmission electron microscope with an in situ laser heating system. The
      structures of the as-deposited and laser annealed films were determined using
      selected area diffraction and the bulk plasmon of AuAl2 and Al realized with
      electron energy loss spectroscopy. Last, the Au-rich solid solution region was
      investigated as a surface enhanced Raman spectroscopy (SERS) substrate using the
      benezenethiol (BT) molecule. Good SERS intensity was maintained up to 30% Al
      addition where enhancements of 105 to 107 were still observed.

PMID- 30277751
TI  - New in Vivo Compatible Matrix Metalloproteinase (MMP)-2 and MMP-9 Inhibitors.
AB  - Matrix metalloproteinases (MMPs) are emerging as pivotal fine-tuners of cell
      function in tissue homeostasis and in various pathologies, in particular
      inflammation. In vivo monitoring of the activity of specific MMPs, therefore,
      provides high potential for assessing disease progression and tissue function,
      and manipulation of MMP activity in tissues and whole organisms may further
      provide a mode of controlling pathological processes. We describe here the
      synthesis of novel fluorinated and nonfluorinated analogues of a secondary
      sulfonamide-based lead structure, compound 2, and test their efficacy as in vivo
      inhibitors and tracers of the gelatinases, MMP-2 and MMP-9. Using a murine
      neuroinflammatory model, we show that compound 2 is a highly effective in vivo
      inhibitor of both MMP-2 and MMP-9 activity with little or no adverse effects even
      after long-term daily oral administration. A fluorescein-labeled derivative
      compound 17 shows direct binding to activated gelatinases surrounding
      inflammatory cuffs in the neuroinflammation model and to pancreatic beta-cells in
      the islets of Langerhans, colocalizing with MMP-2 and MMP-9 activity as detected
      using in situ zymography techniques. These results demonstrate that compound 2
      derivatives have potential as in vivo imaging tools and for future development
      for specific MMP-2 versus MMP-9 probes. Our chemical modifications mainly target
      the residues directed toward the S1' and S2' pockets and, thereby, provide new
      information on the structure-activity relationships of this inhibitor type.

PMID- 30277752
TI  - Self-Damaging Aerobic Reduction of Graphene Oxide by Escherichia coli: Role of GO
      Mediated Extracellular Superoxide Formation.
AB  - Microbial reduction of graphene oxide (GO) under aerobic conditions is poorly
      understood despite its critical role in changing GO toxicity and environmental
      fate. Here we show that 20 mg/L GO interacts with the membrane-bound cytochrome c
      of E. coli in saline, shuttling electrons from the respiratory chain to
      extracellular molecular oxygen. This results in the formation of superoxide
      anions (O2?-), which in turn reduce GO in 30 min. The critical role of superoxide
      was demonstrated by impeding GO reduction upon addition of superoxide dismutase,
      or by carrying out experiments under strictly anaerobic conditions that preclude
      O2?- formation. Coating GO with bovine serum albumin also stopped GO reduction,
      which indicates the need for direct contact between GO and the cell membrane.
      Cell death was observed as a consequence of GO bioreduction. Apparently, electron
      shuttling by GO (via membrane contact) interrupts the respiratory chain and
      induces oxidative stress, as indicated by a 20% decrease in electron transport
      activity and an increase in intracellular reactive oxygen species. This novel
      antimicrobial mechanism could be relevant to assess GO stability and
      biocompatibility, and informs potential applications for microbial control.

PMID- 30277753
TI  - Mechanistic Insight into the Binding Profile of DCVJ and alpha-Synuclein Fibril
      Revealed by Multiscale Simulations.
AB  - Parkinson's disease (PD) is a serious neurodegenerative disease and is
      characterized by abnormal alpha-synuclein (alpha-syn) accumulation in Lewy bodies
      (LB) and Lewy neurites (LN), which makes alpha-syn an important imaging target
      for PD. An imaging probe that quantifies fibrillar alpha-syn can enhance the
      clinical diagnosis of PD and can also be used to evaluate the efficacy of
      therapeutics aimed at reducing the abnormal aggregation of the alpha-syn fibril
      in the brain. In this paper, we study the binding profile of fibrillar alpha-syn
      with a fluorescent probe 4-(dicyanovinyl)julolidine (DCVJ), which is being
      explored for identifying alpha-syn imaging agents. A multiscale simulation
      workflow including molecular docking, molecular dynamics, metadynamics, and QM/MM
      calculations was implemented. We find that DCVJ can bind to multiple sites of
      alpha-syn which are located either at the surface or in the core. Free energy
      calculations using implicit solvent models reveal that the most favorable binding
      mode for DCVJ is associated with the core binding site and is further confirmed
      by metadyamics simulation. Besides, a dynamic binding pathway is discovered,
      which reveals that DCVJ binds gradually into the core of the fibril passing
      through several intermediate states. The conformational arrest of the dicyano
      vinyl group in the fibrillar environment could explain the reason behind the
      fibril-specific fluorescence of DCVJ. Furthermore, based on hybrid QM/MM
      calculations, the molecular geometry of the dicyano vinyl group is found to be
      environment specific which explains why DCVJ serves as a staining agent for such
      fibrillar-like environments. Our results could be helpful for elucidating the
      binding mechanism of imaging tracers with the fibrillar form of alpha-syn and
      explain their fibrillar-specific optical properties, a knowledge that in turn can
      be used to guide the design and development of compounds with higher affinity and
      selectivity for alpha-syn using structure-based strategies.

PMID- 30277754
TI  - Improving the Photostability of Semiconducting Polymer Dots Using Buffers.
AB  - The photostability of fluorescent probes is critical in biological imaging,
      especially for long-term observational analyses. Here, we describe a simple and
      universal method to improve the photostability of semiconducting polymer dots
      (Pdots) and other fluorescent probes by using buffers. Using Pdots as a model
      system, we found that HEPES or MES buffer can improve the photostability of Pdots
      by a factor of 20. Through a systematic study, we show that Pdot photobleaching
      is dominated by photoinduced radicals which can be quenched by the piperazine or
      morpholine structures of these buffers, which act as radical scavengers. For
      conditions where choice of buffer is limited, we designed fluorescent polymers
      conjugated with radical scavengers to improve Pdot photostability. We then
      demonstrate a practical application in which HEPES buffer is used to improve the
      photostability of Pdots during cell imaging.

PMID- 30277755
TI  - Polymer-Ligand-Based ELISA for Robust, High-Throughput, Quantitative Detection of
      p53 Aggregates.
AB  - A growing number of diseases are being linked to protein misfolding and amyloid
      formation. Recently, p53 was also shown to associate into amyloid aggregates,
      raising the question of whether cancer development is associated with protein
      aggregation as well. However, a lack of suitable tools has hampered the
      evaluation of their clinical relevance. Herein, we report an enzyme-linked
      immunosorbent-assay (ELISA) system based on a polyionic, high-molecular-weight
      ligand that specifically captures aggregated oligomers and amyloid proteins. We
      proved that naturally occurring tetramers of p53 are not bound, but high
      molecular-weight aggregates are bound and subsequently detected. For the first
      time, this assay allows the quantitative detection of p53 aggregates from cell
      lysates, which was demonstrated using 22 ovarian-cancer cell lines as well as 7
      patient-derived tumor tissues. The levels of p53 aggregates within the missense
      mutated tissue samples varied more than 12-fold. This simple, robust method
      allows studying the abundance and clinical relevance of protein aggregates. This
      could help our understanding of the role of protein misfolding in cancer or even
      in predicting therapy responses to aggregation-targeting drugs.

PMID- 30277756
TI  - Coupled X-ray Fluorescence and X-ray Absorption Spectroscopy for Microscale
      Imaging and Identification of Sulfur Species within Tissues and Skeletons of
      Scleractinian Corals.
AB  - Identifying and mapping the wide range of sulfur species within complex matrices
      presents a challenge for understanding the distribution of these important
      biomolecules within environmental and biological systems. Here, we present a
      coupled micro X-ray fluorescence (MUXRF) and X-ray absorption near-edge structure
      (XANES) spectroscopy method for determining the presence of specific sulfur
      species in coral tissues and skeletons at high spatial resolution. By using
      multiple energy stacks and principal component analysis of a large spectral
      database, we were able to more accurately identify sulfur species components and
      distinguish different species and distributions of sulfur formerly unresolved by
      previous studies. Specifically, coral tissues were dominated by more reduced
      sulfur species, such as glutathione disulfide, cysteine, and sulfoxide, as well
      as organic sulfate as represented by chondroitin sulfate. Sulfoxide distributions
      were visually correlated with the presence of zooxanthellae endosymbionts. Coral
      skeletons were composed primarily of carbonate-associated sulfate (CAS) along
      with minor contributions from organic sulfate and a separate inorganic sulfate
      likely in the form of adsorbed sulfate. This coupled XRF-XANES approach allows
      for a more accurate and informative view of sulfur within biological systems in
      situ and holds great promise for pairing with other techniques to allow for a
      more encompassing understanding of elemental distributions within the
      environment.

PMID- 30277757
TI  - Characteristics of tire wear particles generated by a tire simulator under
      various driving conditions.
AB  - Physicochemical properties of pure tire wear particles (TWPs) were investigated
      in a laboratory. A tire simulator installed in an enclosing chamber was employed
      to eliminate artifacts caused by interfering particles during the generation and
      measurement of TWPs. TWP particulate matter (PM2.5 and PM10) was correlated with
      tire speed (r > 0.94) and load (r > 0.99). Their mass size distributions showed
      that TWP mode diameters ranged between 3 and 4 MUm (unimodal). Tire wear caused
      by slip events resulted in an increase in the number concentration (ca. 8.4 * 105
      cm-3) of particles (mainly ultrafine particles (UFPs)) at low PM2.5 and PM10
      values (1 and 2 MUg m-3, respectively). During braking events, UFPs were emitted
      at an early stage, with an increase in number concentration (up to 1.1 * 107 cm
      3); a high mass concentration (3.6 mg m-3) was observed at a later stage via the
      coagulation of early emitted UFPs and condensation. On the basis of morphology
      and elemental composition, TWPs generally had elongated (micron-scale) and
      round/irregular (submicron-scale) shapes and they were classified into C/Si-rich,
      heavy metal-containing, S-containing, and mineral-containing particles. This
      study determined that TWP emissions can vary with changes in driving condition.

PMID- 30277758
TI  - PIVOTAL ROLE OF SNOW DEPOSITION AND MELTING DRIVING FLUXES OF POLYCYCLIC AROMATIC
      HYDROCARBONS AT COASTAL LIVINGSTON ISLAND (ANTARCTICA).
AB  - The atmosphere-land-ocean dynamics of semivolatile organic compounds in polar
      regions is poorly understood, also for the abundant and ubiquitous polycyclic
      aromatic hydrocarbons (PAHs). We report the concentrations and fluxes of PAHs in
      a polar coastal ecosystem (Livingston Island, Antarctica). From late spring
      (December 2014) to late summer (February 2015), we sampled air, snow, coastal
      seawater, plankton, and the fugacity in soils and snow. The concentrations of
      PAHs in seawater were low but increased during the austral summer. The PAH
      concentrations in snow were significantly higher than in coastal seawater. Soil
      air fugacity ratios showed a net volatilization of PAH when soils were covered
      with lichens, and close to air-soil equilibrium for bare soils. Concentrations in
      surface snow were also close to equilibrium with atmospheric PAHs. Conversely,
      there was a net diffusive deposition of PAHs to coastal seawater during late
      spring, but a net volatilization from seawater during late summer. Volatilization
      fluxes were correlated with seawater temperature and salinity, consistent with a
      key role of snow-melt to the fluxes and dissolved phase concentrations during the
      austral summer. The comprehensive assessment provided here shows that the
      fugacity amplification in snow is transferred to soils and coastal seawater
      supporting PAH concentrations and fluxes.

PMID- 30277759
TI  - Biocompatibility of Magnetic Resonance Imaging Nanoprobes Improved by
      Transformable Gadolinium Oxide Nanocoils.
AB  - To design functional nanomaterials for biomedical applications, the challenge for
      scientists is to gain further understanding of their unique toxicological
      properties. Nonspecific adhesion of proteins and endocytosis are considered to be
      the major biotoxic sources of imaging nanoprobes. Here, we fabricated ultrathin
      gadolinium oxide (Gd2O3) nanocoils with a low Young's modulus, which provides
      transformable properties in solution. The spatial configurational freedom of
      ultrathin nanocoils induces the steric repulsion to the nonspecific adsorption of
      proteins that, in turn, suppresses cellular uptake and thus improves their
      biocompatibility. The larger number of exposed surface gadolinium atoms of the
      ultrathin nanocoils provided enhanced T1 magnetic resonance (MR) imaging contrast
      with high signal activation. Such nanocontrast agents were applied to in vivo MR
      bioimaging to achieve prolonged circulation lifetime. The improved
      biocompatibility by transformable Gd2O3 nanocoils could open up a new perspective
      toward the design and construction of various nano-biomedicines in the future.

PMID- 30277760
TI  - Scalable and Highly Diastereo- and Enantioselective Catalytic Diels-Alder
      Reaction of alpha,beta-Unsaturated Methyl Esters.
AB  - Despite tremendous advances in enantioselective catalysis of the Diels-Alder
      reaction, the use of simple alpha,beta-unsaturated esters, one of the most
      abundant and useful class of dienophiles, is still severely limited in scope due
      to their low reactivity. We report here a catalytic asymmetric Diels-Alder
      methodology for a large variety of alpha,beta-unsaturated methyl esters and
      different dienes based on extremely reactive silylium imidodiphosphorimidate
      (IDPi) Lewis acids. Mechanistic insights from accurate domain-based local pair
      natural orbital coupled-cluster (DLPNO-CCSD(T)) calculations rationalize the
      catalyst control and stereochemical outcome.

PMID- 30277761
TI  - Lymph-Node-Targeted Immune Activation by Engineered Block Copolymer Amphiphiles
      TLR7/8 Agonist Conjugates.
AB  - Small molecule immuno-modulators such as agonists of Toll-like receptors (TLRs)
      are attractive compounds to stimulate innate immune cells toward potent antiviral
      and antitumor responses. However, small molecules rapidly enter the systemic
      circulation and cause "wasted inflammation". Hence, synthetic strategies to
      confine their radius of action to lymphoid tissue are of great relevance, to both
      enhance their efficacy and concomitantly limit toxicity. Here, we demonstrate
      that covalent conjugation of a small molecule TLR7/8 agonist immunomodulatory to
      a micelle-forming amphiphilic block copolymer greatly alters the pharmacokinetic
      profile, resulting in highly efficient lymphatic delivery. Moreover, we designed
      amphiphilic block copolymers in such a way to form thermodynamically stable
      micelles through pi-pi stacking between aromatic moieties, and we engineered the
      block copolymers to undergo an irreversible amphiphilic to hydrophilic transition
      in response to the acidic endosomal pH.

PMID- 30277762
TI  - An ESIPT Probe for the Ratiometric Imaging of Peroxynitrite Facilitated by
      Binding to Abeta-Aggregates.
AB  - A series of 3-hydroxyflavone (3-HF) ESIPT (excited-state intramolecular proton
      transfer) boronate-based fluorescent probes have been developed for the detection
      of peroxynitrite (ONOO-). The dyes are environmentally sensitive, and each probe
      exhibited a ratiometric response toward ONOO- in a micellar environment. The
      probes were used to image different aggregation states of amyloid-beta (Abeta) in
      the presence of ONOO-. The 3-HF-OMe probe was found to produce a ratiometric
      response toward ONOO- when bound to Abeta aggregates, resulting in a novel host
      guest ensemble, which adds insight into the development of other ESIPT-based
      probes for the simultaneous sensing of fibrous proteins/peptides and
      environmental ROS/RNS.

PMID- 30277763
TI  - Photochemistry of the 1,6-Dideuterio-1,3,5-hexatrienes in Solution: Efficient
      Terminal Bond Photoisomerization in One-Bond-Twist and Bicycle Pedal Ways.
AB  - The report that the central bond photoisomerization of the 1,3,5-hexatrienes
      (Hts) is highly inefficient has encouraged theoreticians to seek conical
      intersections (CIs) at geometries that can explain rapid nonradiative return to
      the initially excited isomer. Because they are photochemically silent, torsional
      relaxations about the terminal double bonds of the Hts have not been evaluated as
      significant radiationless decay pathways. Study of the photoisomerization of
      trans,trans,trans- and trans,cis,trans-1,6-dideuterio-1,3,5-hexatrienes ( ttt-
      and tct-Htd2) addresses this issue. Degassed cyclohexane- d12 (C6D12) and CD3CN
      solutions were irradiated at 254 nm in quartz NMR tubes, and the progress of the
      reactions was followed by 1H NMR. Photoisomerization rates based on the
      integration of terminal hydrogen NMR peaks are in reasonable agreement with rates
      obtained by fitting pure isomer NMR spectra to the phase shift and baseline
      corrected experimental NMR spectra. The results show that terminal bond
      isomerization is highly efficient, especially when one considers that central
      bond isomerization is much more efficient than previously reported and is mainly
      observed together with terminal bond isomerization. A mechanism involving
      terminal one-bond-twist (OBT) in competition with a bicycle pedal (BP) process
      accounts for all terminal and most central bond photoisomerization. OBT central
      bond isomerization is a minor reaction that is observed primarily in the tct to
      ttt direction. Most surprising is the prominent role of the BP process in central
      bond photoisomerization. Proposed initially to account for photoisomerization in
      free volume constraining media, it is observed here in the absence of medium
      constraints.

PMID- 30277764
TI  - Discerning the Redox-Dependent Electronic and Interfacial Structures in
      Electroactive Self-Assembled Monolayers.
AB  - We explore the redox-dependent electronic and structural changes of ferrocene
      terminated self-assembled monolayers (Fc SAMs) immersed in aqueous solution. By
      exploiting X-ray and ultraviolet photoelectron spectroscopy combined with an
      electrochemical cell (EC-XPS/UPS), we can electrochemically control the Fc SAMs
      and spectroscopically probe the induced changes with the ferrocene/ferrocenium
      (Fc/Fc+) redox center (Fe oxidation state), formation of 1:1 Fc+-ClO4- ion pairs,
      molecular orientation, and monolayer thickness. We further find the insignificant
      involvement of interfacial water in the Fc SAMs irrespective of redox state.
      Electrolyte dependencies could be identified with 0.1 M NaClO4 and HClO4 when
      probing partially oxidized Fc/Fc+ SAMs. Corroborating the occurrence of
      electrochemically induced oxidation, EC-UPS shows that oxidation to Fc+ is
      accompanied by a shift of the highest occupied molecular orbital toward higher
      binding energy. The oxidation to Fc+ is also met with an increase in work
      function ascribed to the induced negative interfacial dipole caused by the
      presence of Fc+-ClO4- ion pairs along with a contribution from the reorientation
      of the Fc+ SAMs. The reversibility of our observations is confirmed upon
      conversion from Fc+ back to the neutral Fc. The approach shown here is beneficial
      for a broad range of redox-responsive systems to aid in the elucidation of
      structure-function relationships.

PMID- 30277765
TI  - Characterization and Thermal Denaturation Kinetic Analysis of Recombinant l-Amino
      Acid Ester Hydrolase from Stenotrophomonas maltophilia.
AB  - Stenotrophomonas maltophilia HS1 exhibits l-amino acid ester hydrolase (SmAEH)
      activity, which can synthesize dipeptides such as Ile-Trp, Val-Gly, and Trp-His
      from the corresponding amino acid methyl esters and amino acids. The gene
      encoding SmAEH was cloned and expressed in Escherichia coli and was purified and
      characterized. SmAEH shared 77% sequence identity with a known amino acid ester
      hydrolase (AEH) from Xanthomonas citri, which belongs to a class of beta-lactam
      antibiotic acylases. The thermal stability of SmAEH was evaluated using various
      mathematical models to assess its industrial potential. First-order kinetics
      provided the best description for the inactivation of the enzyme over a
      temperature range of 35-50  degrees C. Decimal reduction time ranged from 212.76
      to 3.44 min, with a z value of 8.06  degrees C, and the deactivation energy was
      204.1 kJ mol-1.

PMID- 30277766
TI  - Computational Mechanism Study on Allylic Oxidation of cis-Internal Alkenes:
      Insight into the Lewis Acid-Assisted Bronsted Acid (LBA) Catalysis in Heteroene
      Reactions.
AB  - The catalytic allylic C-H oxidation of alkenes plays an important role in the
      field of medicine chemistry. Recently, Tambar et al. improved this transformation
      via a heteroene reaction with the assistance of a Lewis acid-assisted chiral
      Bronsted acid (LBA) and achieved a selective allylic oxidation of inactivated cis
      internal alkenes to versatile oxidation products. By means of density functional
      theory (DFT) calculations, we provided a detailed investigation on the mechanism
      of the heteroene reaction and successfully located a new catalytic process, which
      is able to explain the experimental observations very well. Four different
      reactive pathways (pathways A, B, C, and D) for the LBA-catalyzed heteroene
      reaction have been designed. We found pathway D, which undergoes a protonation
      process for the activation of enophile benzenesulfonyl sulfurimide, has the
      lowest overall free energy barrier. Pathway E was put forward to lead to a minor
      enantiomer. The theoretical enantiomeric ratio calculated via their energy
      difference is consistent with the experimental report. For the heteroene
      reaction, we proposed a new reaction mechanism, which can assist in related
      transformations and the design of new LBA catalysts.

PMID- 30277767
TI  - A Toolbox Approach To Construct Broadly Applicable Metal-Free Catalysts for
      Photoredox Chemistry: Deliberate Tuning of Redox Potentials and Importance of
      Halogens in Donor-Acceptor Cyanoarenes.
AB  - The targeted choice of specific photocatalysts has been shown to play a critical
      role for the successful realization of challenging photoredox catalytic
      transformations. Herein, we demonstrate the successful implementation of a
      rational design strategy for a series of deliberate structural manipulations of
      cyanoarene-based, purely organic donor-acceptor photocatalysts, using 1,2,3,5
      tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) as a starting point.
      Systematic modifications of both the donor substituents as well as the acceptors'
      molecular core allowed us to identify strongly oxidizing as well as strongly
      reducing catalysts (e.g., for an unprecedented detriflation of unactivated
      naphthol triflate), which additionally offer remarkably balanced redox potentials
      with predictable trends. Especially halogen arene core substitutions are
      instrumental for our targeted alterations of the catalysts' redox properties.
      Based on their preeminent electrochemical and photophysical characteristics, all
      novel, purely organic photoredox catalysts were evaluated in three challenging,
      mechanistically distinct classes of benchmark reactions (either requiring
      balanced, highly oxidizing or strongly reducing properties) to demonstrate their
      enormous potential as customizable photocatalysts, that outperform and complement
      prevailing typical best photocatalysts.

PMID- 30277768
TI  - Effect of Structure on the Spin-Spin Interactions of Tethered Dicyanomethyl
      Diradicals.
AB  - Stable organic radicals with switchable spin states have attracted attention for
      a variety of applications, but a fundamental understanding of how radical
      structure effects the weak bonding interactions between organic radicals is
      limited. To evaluate the effect of chemical structure on the strength and nature
      of such spin interactions, a series of 14 tethered aryl dicyanomethyl diradicals
      were synthesized, and the structure and thermodynamic properties of the
      diradicals were investigated. These studies indicate that the nature of the dimer
      and the equilibrium thermodynamic parameters of the diradical-dimer equilibria
      are highly sensitive to the attachment point of the linker, the length of the
      linker, and the substituents on the radical itself. Values of the intramolecular
      Ka vary from as small as 5 to as high as 105 depending on these variables. An X
      ray crystal structure for a linked ortho-substituted diradical shows that the
      diradical forms an intramolecular sigma dimer in the crystalline state with an
      elongated C-C bond (1.637 A). Subtle changes to the radical structure influences
      the nature of the spin interactions, as fixing the dimethylamino substituent on
      the radical into a ring to make a julolidine-derived diradical leads to the
      weakest bonding interaction observed (Delta Gbonding = 1 kcal mol-1) and changes
      the spin-paired species from a sigma dimer to a diradical pimer. This work has
      implications for the design of stimuli-responsive materials that can reversibly
      switch between the dramatically different properties of closed-shell species and
      the unique properties of diradicals.

PMID- 30277769
TI  - Women in Computational Chemistry.

PMID- 30277770
TI  - Citrus kawachiensis Peel Powder Reduces Intestinal Barrier Defects and
      Inflammation in Colitic Mice.
AB  - The anti-inflammatory effect of Citrus kawachiensis peel powder was examined in a
      murine model of dextran sodium sulfate (DSS)-induced colitic mice. In addition to
      the whole powder, its ethanol extract rich in polyphenolic compounds and ethanol
      extraction residue rich in dietary fibers were used. The whole powder ameliorated
      the DSS-induced body weight loss (body weight changes on day 9, Control 108 +/-
      2, DSS 91 +/- 4, DSS+whole peel powder 106 +/- 1%, p < 0.05), colon shortening
      (colon length, Control 5.0 +/- 0.1, DSS 3.9 +/- 0.1, DSS+whole peel powder 4.7 +/
      0.1 cm, p < 0.05), increased expression of pro-inflammatory cytokines (e.g., TNF
      alpha, Control 1.0 +/- 0.1, DSS 22.2 +/- 5.8, DSS+whole peel powder 4.3 +/- 1.5
      arbitrary unit, p < 0.05), and decreased expression of colonic tight junctions
      (TJs) (e.g., occludin, Control 1.00 +/- 0.07, DSS 0.21 +/- 0.07, DSS+whole peel
      powder 0.70 +/- 0.06 arbitrary unit, p < 0.05). The resolution of abnormalities
      barring the decreased expression of zonula occludens-2, junctional adhesion
      molecule-A, and claudin-7 by the extraction residue was comparable to that
      achieved using the powder (body weight change 107 +/- 1%; colon length 4.7 +/-
      0.1 cm; TNF-alpha 4.1 +/- 0.7; occludin 0.58 +/- 0.06 arbitrary unit, p < 0.05).
      The ethanol extract alone did not have any influence on these abnormalities (body
      weight change 94 +/- 2%; colon length 4.1 +/- 0.1 cm; TNF-alpha 40.5 +/- 9.0
      arbitrary unit; occludin 0.18 +/- 0.02 arbitrary unit, p < 0.05). The powder and
      ethanol extraction residue, but not ethanol extract, increased fecal acetic acid
      concentration (Control 4.9 +/- 0.6, DSS 5.0 +/- 0.9, DSS+whole peel powder 8.8 +/
      1.8, DSS+ethanol extract 5.3 +/- 0.8, DSS+ethanol extraction residue 12.5 +/-
      1.1 mmol/L, p < 0.05). Taken together, DFs in the ethanol extraction residue
      largely contributed to the peel powder-mediated reduction of TJ barrier defect
      and inflammation in colitic mice.

PMID- 30277771
TI  - Donor-Acceptor Fluorophores for Energy-Transfer-Mediated Photocatalysis.
AB  - Triplet-triplet energy transfer (EnT) is a fundamental activation pathway in
      photocatalysis. In this work, we report the mechanistic origins of the triplet
      excited state of carbazole-cyanobenzene donor-acceptor (D-A) fluorophores in EnT
      based photocatalytic reactions and demonstrate the key factors that control the
      accessibility of the 3LE (locally excited triplet state) and 3CT (charge-transfer
      triplet state) via a combined photochemical and transient absorption
      spectroscopic study. We found that the energy order between 1CT (charge transfer
      singlet state) and 3LE dictates the accessibility of 3LE/3CT for EnT, which can
      be effectively engineered by varying solvent polarity and D-A character to
      depopulate 3LE and facilitate EnT from the chemically more tunable 3CT state for
      photosensitization. Following the above design principle, a new D-A fluorophore
      with strong D-A character and weak redox potential is identified, which exhibits
      high efficiency for Ni(II)-catalyzed cross-coupling of carboxylic acids and aryl
      halides with a wide substrate scope and high selectivity. Our results not only
      provide key fundamental insight on the EnT mechanism of D-A fluorophores but also
      establish its wide utility in EnT-mediated photocatalytic reactions.

PMID- 30277772
TI  - Predicting the Initial Thermal Decomposition Path of Nitrobenzene Caused by Mode
      Vibration at Moderate-Low Temperatures: Temperature-Dependent Anti-Stokes Raman
      Spectra Experiments and First-Principals Calculations.
AB  - The lack of understanding of the initial decomposition micromechanism of
      energetic materials subjected to external stimulation has hindered its safe
      storage, usage, and development. The initial thermal decomposition path of
      nitrobenzene triggered by molecular thermal motion is investigated using
      temperature-dependent anti-Stokes Raman spectra experiments and first-principles
      calculations to clarify the initial thermal decomposition micromechanism. The
      experiment shows that the symmetric nitro stretching, antisymmetric nitro
      stretching, and phenyl ring stretching vibration modes are active as increasing
      temperature below 500 K. The DFT method is used to examine the effects of the
      three mode vibrations on the initial decomposition of nitrobenzene by relaxed
      scan for each relevant change in bond lengths and bond angles to obtain the
      optimal reaction channel leading to initial thermal decomposition of
      nitrobenzene. The results demonstrate that the initial thermal decomposition is
      the isomerization of nitrobenzene to phenyl nitrite. The optimal reaction channel
      leading to the initial isomerization is the increase or decrease of angle O-N-C
      from the antisymmetric nitro stretching vibration, which causes the torsion of
      nitro group and the subsequent oxygen atom attacking carbon atom. The scanning
      energy barrier related to angle O-N-C is about 62.1 kcal/mol, which is very
      consistent with the calculated activation barrier of isomerization of
      nitrobenzene. This proves the reliability of our conclusions.

PMID- 30277774
TI  - Syntheses of Cyclopropyl Analogues of Disorazoles A1 and B1 and Their Thiazole
      Counterparts.
AB  - Modular syntheses of disorazoles A1 and B1 analogues in which the epoxide
      moieties of the natural products were replaced with cyclopropyl units have been
      achieved. Targeted as part of a structure-activity relationships study, these
      syntheses were successfully extended to the thiazole counterparts of these
      analogues. The retrosynthetically defined fragments were assembled through
      Yamaguchi esterification, Cu/Pd-catalyzed cross-coupling, Yamaguchi
      macrolactonization, and Cu-catalyzed cross-coupling as the key reactions. Further
      synthetic and biological investigations of such analogues are expected to lead to
      the discovery and development of potential payloads for antibody-drug conjugates
      as targeted cancer therapies.

PMID- 30277773
TI  - Reactivity of Hydroxyl Radical in Nonaqueous Phases: Addition Reactions.
AB  - The effect of ring substitution on the kinetics of reaction of arenes,
      heterocycles, and alkenes with hydroxyl radical is investigated in terms of
      reactivity and selectivity, using laser flash photolysis (LFP) in acetonitrile
      solution. The LFP data indicate that charge-transfer contributions in the
      transition state play an important role in dictating reactivity, and there is a
      correlation between the experimental and calculated ionization potentials of the
      arenes and alkenes and their respective reactivities. The reactivity observed for
      arenes in acetonitrile exhibits a much greater sensitivity toward substitution on
      the ring than in water, and therefore aqueous data cannot be used to predict
      reactivity in nonaqueous environments. Nonaqueous solution data may be
      predictable from gas phase data, and vice versa.

PMID- 30277775
TI  - Planar Pentacoordinate versus Tetracoordinate Carbons in Ternary CBe4Li4 and
      CBe4Li42- Clusters.
AB  - Planar hypercoordinate carbon molecules are exotic species, for which the 18
      electron counting has been considered a rule. We report herein computational
      evidence of perfectly planar C2 v CBe4Li4 (1) and D4 h CBe4Li42- (3) clusters.
      These ternary species contain 16 and 18 electrons, respectively. The dianion is
      highly symmetric with a planar tetracoordinate carbon (ptC), whereas the neutral
      features a planar pentacoordinate carbon (ppC). Thus, charge-state alters the
      coordination environments of a cluster. Chemical bonding analysis shows that both
      clusters have 2pi and 6sigma delocalization around the C center, suggesting that
      ppC or ptC clusters are governed by double pi/sigma aromaticity, rather than the
      18-electron rule. The outer Be4Li4 ring in 1 and 3 also supports 2sigma
      aromaticity, collectively leading to 3-fold pi/sigma aromaticity for these
      ppC/ptC clusters. Structural transformation from ptC (3) to ppC (1) is discussed,
      in which the 16-electron quasi-ptC CBe4Li4 (2) cluster serves as an intermediate.
      Cluster 2 as a local minimum has severe out-of-plane distortion. Flattening of 2
      leads to reorganization of Be4 ring around the C center, which offers space for
      the fifth atom to coordinate and facilitates ppC formation. The latter
      arrangement optimizes pi aromaticity and better manages intramolecular Coulomb
      repulsion. This work highlights the geometric factor (and unconventional electron
      counting) in the design of planar hypercoordinate carbons.

PMID- 30277776
TI  - Rotational Excitation of HD by Hydrogen Revisited.
AB  - The HD molecules are key species for the cooling of pristine gas at temperatures
      below 100 K. They are also known to be key tracers of H2 in protoplanetary disks
      and thus, they can be used as a measure of protoplanetary disks mass. Accurate
      modeling of the cooling mechanism and of HD abundance in astrophysical media
      requires a proper modeling for its excitation by both radiative and collisional
      processes. Here, we report quantum time-independent calculations of collisional
      rate coefficients for the rotational excitation of HD by H for temperatures
      ranging from 10 to 1000 K. The reactive and hydrogen exchange channels are taken
      into account in the scattering calculations. New exact quantum results are
      compared to previous calculations performed neglecting reactive and exchange
      channels. We found that for temperatures higher than ~300 K, the impact of these
      channels on the rate coefficients cannot be neglected. Such results suggest that
      the new HD-H collisional data have to be used for properly modeling HD cooling
      function and HD abundance in all the astrophysical environments where HD plays a
      role, e.g. in photon-dominated regions, protoplanetary disks, early Universe
      chemistry, and primordial star forming regions.

PMID- 30277777
TI  - Advances in surface passivation of nanoscale zerovalent iron (NZVI): A critical
      review.
AB  - Nanoscale zerovalent iron (NZVI) is one of the most extensively studied
      nanomaterials in the fields of wastewater treatment and remediation of soil and
      groundwater. However, rapid oxidative transformations of NZVI can result in
      reduced NZVI reactivity. Indeed, the surface passivation of NZVI is considered
      one of the most challenging aspects in successfully applying NZVI to contaminant
      degradation. The oxidation of NZVI can lead to the formation of FeII-bearing
      phases (e.g., FeIIO, FeII(OH)2, FeIIFeIII2O4) on the NZVI surface or complete
      oxidation to ferric (oxyhydr)oxides (e.g., FeIIIOOH). This corrosion phenomenon
      is dependent upon various factors including the composition of NZVI itself, the
      type and concentration of aqueous species, reaction time and oxic/anoxic
      environments. As such, the co-existence of different Fe oxidation states on NZVI
      surfaces may also, in some instances, provide a unique reactive microenvironment
      to promote the adsorption of contaminants and their subsequent transformation via
      redox reactions. Thus, an understanding of passivation chemistry, and its related
      mechanisms, is essential not only for effective NZVI application but also for
      accurately assessing the positive and negative effects of NZVI surface
      passivation. The aim of this review is to discuss the nature of the passivation
      processes that occur and the passivation byproducts that form in various
      environments. In particular, the review presents: i) the strengths and
      limitations of state-of-the-art techniques (e.g., electron microscopies and X-ray
      based spectroscopies) to identify passivation byproducts; ii) the passivation
      mechanisms proposed to occur in anoxic and oxic environments; and iii) the
      effects arising from synthesis procedures and the presence of inorganics/organics
      on the nature of the passivation byproducts that form. In addition, several
      depassivation strategies that may assist in increasing and/or maintaining the
      reactivity of NZVI are considered, thereby enhancing the effectiveness of NZVI in
      contaminant degradation.

PMID- 30277778
TI  - Atomistic Insight into the Electrochemical Double Layer of Choline Chloride-Urea
      Deep Eutectic Solvents: Clustered Interfacial Structuring.
AB  - Green, stable, and wide electrochemical window deep eutectic solvents (DESs) are
      ideal candidates for electrochemical systems. However, despite several studies of
      their bulk properties, their structure and properties under electrified
      confinement have barely been investigated, which has hindered widespread use of
      these solvents in electrochemical applications. In this Letter, we explore the
      electrical double layer structure of 1:2 choline chloride-urea (Reline), with a
      particular focus on the electrosorption of the hydrogen bond donor on a graphene
      electrode using atomistic molecular dynamics simulations. We discovered that the
      interface is composed of a mixed layer of urea and counterions followed by a
      mixed charged clustered structure of all of the Reline components. This
      interfacial structuring is strongly dependent on the balance between
      intermolecular interactions and surface polarization. These results provide new
      insights into the electrical double layer structure of a new generation of
      electrolytes whose interfacial structure can be tuned at the molecular level.

PMID- 30277779
TI  - Re-entrant Cavities Enhance Resilience to the Cassie-to-Wenzel State Transition
      on Superhydrophobic Surfaces during Electrowetting.
AB  - Electrowetting-based droplet actuation has applications in digital microfluidics.
      Mobility of droplets on surfaces can be enhanced using structured
      superhydrophobic surfaces that offer inherently low adhesion to droplets in the
      Cassie state. However, these surfaces must be designed to prevent transition to
      the Wenzel state (in which droplets are immobile) at high electrowetting
      actuation voltages. The electrowetting behavior of cylindrical microposts and
      mushroom-shaped re-entrant microstructures, both of which afford excellent
      superhydrophobicity, is investigated and compared. A surface-energy-based model
      is employed to estimate the energy barrier for the Cassie-to-Wenzel transition
      and thus the electrowetting voltage required to initiate this transition. The
      mushroom structures are predicted to be more resilient to transition (i.e.,
      transition occurs at a voltage that is up to 1.5 times higher) than microposts.
      Both types of microstructured surfaces are fabricated and electrowetting
      experiments performed to demonstrate that mushroom structures indeed inhibit the
      Cassie-to-Wenzel transition at voltages that induce such transition on the
      cylindrical microposts.

PMID- 30277780
TI  - High Sensitivity In-Cell EPR Distance Measurements on Proteins using an Optimized
      Gd(III) Spin Label.
AB  - Distance measurements by electron-electron double resonance (DEER) carried out on
      spin-labeled proteins delivered into cells provide new insights into the
      conformational states of proteins in their native environment. Such measurements
      depend on spin labels that exhibit high redox stability and high DEER
      sensitivity. Here we present a new Gd(III)-based spin label, BrPSPy-DO3A-Gd(III),
      which was derived from an earlier label, BrPSPy-DO3MA-Gd(III), by removing the
      methyl group from the methyl acetate pending arms. The small chemical
      modification led to a reduction in the zero-field splitting and to a significant
      increase in the phase memory time, which together culminated in a remarkable
      improvement of in-cell DEER sensitivity, while maintaining the high distance
      resolution. The excellent performance of BrPSPy-DO3A-Gd(III) in in-cell DEER
      measurements was demonstrated on doubly labeled ubiquitin and GB1 delivered into
      HeLa cells by electroporation.

PMID- 30277781
TI  - Digging for Missing Proteins Using Low-Molecular-Weight Protein Enrichment and a
      "Mirror Protease" Strategy.
AB  - In 2012, the Chromosome-Centric Human Proteome Project (C-HPP) launched an
      investigation for missing proteins (MPs) to complete the human proteome project
      (HPP). The majority of the MPs were distributed in low molecular weight (LMW)
      ranges, especially from 0-40 kDa. LMW protein identification is challenging,
      owing to their short length, low abundance, and hydrophobicity. Furthermore, many
      sequences from Trypsin digestion are unlikely to yield detectable peptides or
      reasonable quality of MS2 spectrum. Therefore, we focused on small MPs by
      combining LMW protein enrichment and a pair of complementary proteases strategy
      with Trypsin and LysargiNase for human testis samples. In-depth testis LMW
      protein profiling resulted in the identification of 4,063 proteins, of which
      2,565 were LMW proteins, and 1,130 had paired of peptides generated from both of
      the Trypsin and LysargiNase. This provided additional mass spectral evidence for
      further verification of small MPs. Finally, two MPs were verified from the seven
      MP candidates. One of them, Q8N688 was verified with two series of continuous and
      complementary b/y-product ions from the paired of spectra for tryptic and
      LysargiNase digested peptides after the "mirror spectrum" matching. This make the
      confident identification of the representative peptides for the target MPs. On
      another hand, the two verified peptides for Q86WR6 were identified with the same
      strategy from the gel-separation and gel-elution sample, respectively. Although
      the other five MP candidates showed high quality spectra, they could not be
      sufficiently distinguished as PE1s, and require further verification. All MS
      datasets have been deposited in the ProteomeXchange with identifier PXD010093
      (Username: reviewer01467@ebi.ac.uk; Password: 3UNjNWUA).

PMID- 30277782
TI  - Chemically Immobilized Antimicrobial Peptide on Polymer and Self-Assembled
      Monolayer Substrates.
AB  - Surfaces with chemically immobilized antimicrobial peptides have been shown to
      have great potential in various applications such as biosensors and antimicrobial
      coatings. This research investigated the chemical immobilization of a cecropin
      melittin hybrid antimicrobial peptide on two different surfaces, a polymer
      surface prepared by chemical vapor deposition (CVD) polymerization and a self
      assembled monolayer surface. We probed the structure of immobilized peptides
      using spectroscopic methods and correlated such structural information to the
      measured antimicrobial activity. We found that the hybrid peptide adopts an alpha
      helical structure after immobilization onto both surfaces. As we have shown
      previously for another alpha-helical peptide, MSI-78, immobilized on a SAM, we
      found that the alpha-helical hybrid peptide lies down when it contacts bacteria.
      This study shows that the antimicrobial activity of the surface-immobilized
      peptides on the two substrates can be well explained by the spectroscopically
      measured peptide structural data. In addition, it was found that the polymer
      based antimicrobial peptide coating is more stable. This is likely due to the
      fact that the SAM prepared using silane may be degraded after several days
      whereas the polymer prepared by CVD polymerization is more stable than the SAM,
      leading to a more stable antimicrobial coating.

PMID- 30277783
TI  - Diabatic States at Construction (DAC) through Generalized Singular Value
      Decomposition.
AB  - A procedure, called generalized diabatic-at-construction (GDAC), is presented to
      transform adiabatic potential energy surfaces into a diabatic representation by
      generalized singular value decomposition. First, we use a set of localized,
      valence bond-like configuration state functions, called DAC, as the basis states.
      Then, the adiabatic ground and relevant excited states are determined using
      multistate density functional theory (MSDFT). GDAC differs in the opposite
      direction from traditional approaches based on adiabatic-to-diabatic
      transformation with certain property restraints. The method is illustrated with
      applications to a model first-order bond dissociation reaction of CH3OCH2Cl
      polarized by a solvent molecule, the ground- and first-excited-state potential
      energy surfaces near the minimum conical intersection for the ammonia dimer
      photodissociation, and the multiple avoided curve crossings in the dissociation
      of lithium hydride. The GDAC diabatization method may be useful for defining
      charge-localized states in studies of electron transfer and proton-coupled
      electron transfer reactions in proteins.

PMID- 30277784
TI  - Multiplex Immuno-Liquid Chromatography-Mass Spectrometry-Parallel Reaction
      Monitoring (LC-MS-PRM) Quantitation of CD8A, CD4, LAG3, PD1, PD-L1, and PD-L2 in
      Frozen Human Tissues.
AB  - The immune status of tumors critically influences their responsiveness to PD1
      blockades and other immune-based therapies. Programmed death ligand 1 (PD-L1)
      immunohistochemistry (IHC) is a clinically validated predictive biomarker of
      response to checkpoint-inhibitor therapy in a limited number of clinical settings
      but is poorly predictive in most. With emerging evidence that multiple pathways
      and immune-checkpoint proteins may coordinately contribute to the adaptive immune
      resistance, the identification and quantitation of multiple immune markers in
      tumor tissue could help identify the controlling pathways in a given patient,
      guide the selection of optimal therapy, and monitor response to treatment. We
      developed and validated a sensitive and robust immuno-liquid chromatography
      parallel reaction monitoring assay to simultaneously quantify the expression
      levels of six immune markers (CD8A, CD4, LAG3, PD1, PD-L1, and PD-L2) using as
      little as 1-2 mg of fresh frozen tissue. The lower limit of quantitation ranged
      from 0.07 ng/mg protein for PD1 to 1.0 ng/mg protein for CD4. The intrabatch
      accuracy was within -16.6% to 15.0% for all proteins at all concentrations, and
      the variation ranged from 0.8% to 14.7%, while interbatch accuracy was within 
      6.3% to 8.6%, and the variation ranged from 1.3% to 12.8%. The validated assay
      was then applied to quantify all six biomarkers in different tissues and was
      confirmed to have sufficient sensitivity (0.07-1.00 ng/mg protein) and
      reproducibility (variation ranged from 4.3 to 12.0%). In an analysis of 26
      cervical tumors, CD8A and CD4 were detected in all tumors, followed by PD-L1 in
      85%, LAG-3 in 65%, PD1 in 50%, and PD-L2 in 35%. The strongest correlations were
      observed between CD8A and CD4 ( r = 0.88) and CD8A and LAG-3 ( r = 0.86). PD1 was
      not significantly correlated with any of the other proteins tested. This method
      can be applied to survey the immune signatures across tumor types and tailored to
      incorporate additional markers as needed.

PMID- 30277785
TI  - To Which Extent Is Paramagnetic Solid-State NMR Able To Address Polymorphism in
      Complex Transition-Metal Oxides?
AB  - A detailed characterization of the polymorphs constituting cathode materials,
      both before and after cell cycling, is mandatory to develop more stable and
      powerful lithium batteries. In many cases, e.g., for transition metal lithium
      silicates, standard diffraction techniques cannot give a clear-cut response. Here
      we show that broadband adiabatic fast MAS NMR can give unique information in the
      case of model Li2(Mn,Fe)SiO4 high-capacity cathode materials. By coupling 7Li and
      29Si 1D and 2D spectra, we are able to address polymorphs speciation also in the
      mixed Mn/Fe compositions, which is a nearly impossible task for X-rays and
      neutrons diffraction. We finally discuss the conditions under which this approach
      is useful when applied to rare nuclei such as 29Si.

PMID- 30277786
TI  - Observation of Near-Threshold Resonances in the Flavin Chromophore Anions
      Alloxazine and Lumichrome.
AB  - Lumichrome (LC) is the chromophore of the flavin family of photoactive
      biomolecules, where key biochemical activity involves interplay between redox and
      photophysical events. Questions remain about the relationship between the redox
      status of the ground and excited states and demand an improved understanding of
      the intrinsic photochemistry. Using anion photodissociation spectroscopy, we have
      measured the intrinsic electronic spectroscopy (564-220 nm) and accompanying
      photodegradation pathways of the deprotonated anionic form of LC. Experiments
      were also performed on alloxazine (AL), which is equivalent to LC minus two
      methyl groups. We observe a resonance state close to 3.8 eV for both anions for
      the first time, which we tentatively assign to dipole-bound excited states. For
      AL this state is sufficiently long-lived to facilitate dissociative electron
      attachment. Our results suggest that the presence of methyl group rotors at key
      positions along the molecular dipole may reduce the lifetime of the resonance
      state and hence provide a structural barrier to valence electron capture, and
      ensuing molecular dissociation.

PMID- 30277787
TI  - Plasmon-Driven Photocatalysis Leads to Products Known from E-beam and X-ray
      Induced Surface Chemistry.
AB  - Plasmonic metal nanostructures can concentrate incident optical fields in
      nanometer-sized volumes, called hot spots. This leads to enhanced optical
      responses of molecules in such a hot spot but also to chemical transformations,
      driven by plasmon-induced hot carriers. Here, we employ tip-enhanced Raman
      spectroscopy (TERS) to study the mechanism of these reactions in situ at the
      level of a single hot spot. Direct spectroscopic measurements reveal the energy
      distribution of hot electrons, as well as the temperature changes due to
      plasmonic heating. Therefore, charge-driven reactions can be distinguished from
      thermal reaction pathways. The products of the hot-carrier-driven reactions are
      strikingly similar to the ones known from X-ray or e-beam-induced surface
      chemistry despite the >100-fold energy difference between visible and X-ray
      photons. Understanding the analogies between those two scenarios implies new
      strategies for rational design of plasmonic photocatalytic reactions and for the
      elimination of photoinduced damage in plasmon-enhanced spectroscopy.

PMID- 30277788
TI  - Microlens Enhancement of Surface-Tethered Molecular Beacons.
AB  - The tethering of molecular beacon oligonucleotide detection probes to surface
      patterned poly(ethylene glycol) (PEG) microgels has enabled the integration of
      molecular beacons into a microarray format. The microgels not only localize the
      probes to specific surface positions but also maintain them in a waterlike
      environment. Here we extend the concept of microgel tethering to include
      dielectric microlenses. We show that streptavidin-functionalized polystyrene
      microspheres (3 MUm diameter) can be colocalized with molecular beacons using
      biotinylated PEG gels in patterns ranging from pseudocontinuous microgel pads
      with lateral dimensions on the order of tens of micrometers to individual
      microgels with lateral dimensions on the order of 400-500 nm. We use a simplex
      assay based on Influenza A detection to study the lensing behavior. The
      microspheres increase the effective numerical aperture of the collection optics,
      and we find that a tethered microsphere increases the peak intensity collected
      from hybridized beacons between 1.5 and 10 times depending on the specific
      pattern size and areal density of microgels. The highest signal increase occurs
      when a single microsphere is tethered to a single isolated microgel. The
      tethering is highly self-directed and occurs in the individual-microgel case only
      when the microgel is close to the optic axis of the microsphere. This alignment
      minimizes spherical aberration and maximizes coupling of emitted fluorescent
      intensity into the collection optics.

PMID- 30277789
TI  - Revelation of the Balanol Biosynthetic Pathway in Tolypocladium ophioglossoides.
AB  - A cryptic gene cluster, bln, was activated by genome mining in Tolypocladium
      ophioglossoides. This activation led to the production of balanol and eight other
      metabolites. Gene disruption and metabolite profile analysis showed that the
      biosynthesis of balanol involved the convergence of independent PKS and NRPS
      pathways, and a biosynthetic pathway for balanol was proposed.

PMID- 30277790
TI  - Shaping the Nonlinear Emission Pattern of a Dielectric Nanoantenna by Integrated
      Holographic Gratings.
AB  - We demonstrate the shaping of the second-harmonic (SH) radiation pattern from a
      single AlGaAs nanodisk antenna using coplanar holographic gratings. The SH
      radiation emitted from the antenna toward the-otherwise forbidden-normal
      direction can be effectively redirected by suitably shifting the phase of the
      grating pattern in the azimuthal direction. The use of such gratings allows
      increasing the SH power collection efficiency by 2 orders of magnitude with
      respect to an isolated antenna and demonstrates the possibility of intensity
      tailoring for an arbitrary collection angle. Such reconstruction of the nonlinear
      emission from nanoscale antennas represents the first step toward the application
      of all-dielectric nanostructures for nonlinear holography.

PMID- 30277791
TI  - Origin of Internal Friction in Disordered Proteins Depends on Solvent Quality.
AB  - Protein dynamics often exhibit internal friction; i.e., contributions to friction
      that cannot solely be attributed to the viscosity of the solvent. Remarkably,
      even unfolded and intrinsically disordered proteins (IDPs) exhibit this behavior,
      despite typically being solvent-exposed. Several competing molecular mechanisms
      have been suggested to underlie this phenomenon, in particular dihedral
      relaxation and intrachain interactions. It has also recently been shown that
      single-molecule data reflecting internal friction in the disordered protein ACTR
      cannot be explained using polymer models unless this friction is dependent on
      protein collapse. However, the connection between the collapse of the chain and
      the underlying mechanism of internal friction has been unclear. To address this
      issue, we combine molecular simulation and single-molecule experimental data to
      investigate how chain compaction affects protein dynamics in the context of ACTR.
      Chain reconfiguration times and internal friction estimated from all-atom
      simulations are in semiquantitative agreement with experimental data. We dissect
      the underlying molecular mechanism with all-atom and coarse-grained simulations
      and clearly identify both intrachain interactions and dihedral angle transitions
      as contributions to internal friction. However, their relative contribution is
      strongly dependent on the compactness of the IDP; while dihedral relaxation
      dominates internal friction in expanded configurations, intrachain interactions
      dominate for more compact chains. Our results thus imply a continuous transition
      between mechanisms and provide a link between internal friction in IDPs and that
      in more compact and folded states of proteins.

PMID- 30277792
TI  - Regulation of Catalytic DNA Activities with Thermosensitive Gold Nanoparticle
      Surfaces.
AB  - The regulation of the activities of catalytic DNA is of great importance in many
      applications, especially in biosensing, controllable drug carriers, and gene
      therapy. In this work, the surfaces of gold nanoparticles (AuNPs) are
      simultaneously modified with a thermoresponsive polymer, poly( N
      isopropylacrylamide) (pNIPAM), and catalytic DNA to form thermosensitive
      catalytic DNA/pNIPAM/AuNP systems. The thermosensitive pNIPAM on the surfaces of
      AuNPs enables the temperature-controlled catalytic activities of the system in a
      narrow temperature range. The catalytic DNA/pNIPAM/AuNP system exhibits almost no
      catalytic activity at temperatures below the lower critical solution temperature
      (LCST) of pNIPAM and become highly catalytic when the temperature is higher than
      the LCST. Two kinds of catalytic DNA, the entropy-driven DNA catalytic network
      and the Mg2+-dependent DNAzyme, were chosen as model catalytic systems, and the
      results showed that the regulation of catalytic activities for both systems was
      achieved efficiently. These systems may have important potentials in future
      biosensing and biomedical applications.

PMID- 30277793
TI  - The Regulatory Effects of Brown Adipose Tissue Thermogenesis on Maternal
      Metabolic Adaptation, Placental Efficiency, and Fetal Growth in Mice.
AB  - To determine the role of UCP1-mediated thermogenesis in controlling maternal
      metabolic adaptation to pregnancy, energy metabolism of C57BL/6 wild-type (WT)
      and Ucp1 gene knockout (Ucp1-/-) mice was studied during pregnancy. With the
      progression of pregnancy, maternal energy expenditure rates (EERs), expression of
      UCP1 and core body temperature steadily declined in WT dams. Despite no
      significant alterations in core body temperature and weight gain during
      pregnancy, Ucp1-/- dams exhibited lower rates in EER decline. High-fat (HF)
      feeding not only robustly increased maternal UCP1 expression and core body
      temperature but also abolished gestation-suppressed EER in WT dams. However, HF
      increased EERs were significantly attenuated in Ucp1-/- dams. Significantly
      increased fetal body weights and fetal/placental weight ratio were detected in
      fetuses from Ucp1-/- dams compared with fetuses from WT dams. Markedly increased
      expression levels of glucose transporter 1 and amino acid transporters were also
      observed in placentas from Ucp1-/- dams. Furthermore, blood glucose
      concentrations of fetuses from Ucp1-/- dams were significantly higher than those
      of fetuses from WT dams, indicating that maternal UCP1 has an inhibitory effect
      on placental efficiency and fetal growth. Together, this study demonstrated that
      maternal BAT plays an important role in controlling maternal metabolic adaptation
      and placental nutrient transport.

PMID- 30277794
TI  - Intestinal in vitro cell culture models and their potential to study the effect
      of food components on intestinal inflammation.
AB  - Cell cultures are widely used in pharmaceutical, medical, food/nutrition and
      biological sciences. In food and nutrition science, intestinal cell culture
      models of human origin are attracting increasing interest but are still rarely
      used in investigations of the effects of bioactive food compounds on intestinal
      inflammation. However, such in vitro models would, among other benefits, limit
      the use of in vivo models and could provide new molecular data. This review is an
      overview of two-dimensional (2D) and three-dimensional (3D) intestinal cell
      culture models and their potential use in gut inflammation studies. After
      describing the features of healthy and inflamed intestinal barriers, we describe
      the main intestinal cell lines (Caco2, HT29, T84) and their use in investigations
      of the transport and antioxidant/anti-inflammatory potential of some bioactive
      food compounds. Finally, different co-culture models of gut inflammation, in
      association with immune cells (PBMC, THP1 and RAW 264.7 cell lines) in both 2D
      and 3D models are presented. 3D models called organs-on-chips or biochips are the
      most recent and very promising approach made possible by bioengineering and
      biotechnological improvements and more accurately mimic the gut microenvironment.

PMID- 30277795
TI  - S100A8 Protects Human Primary Alveolar Type II Cells Against Injury and
      Emphysema.
AB  - Pulmonary emphysema is characterized by alveolar wall destruction and cigarette
      smoking is the main factor of this disease development. S100A8 is a member of the
      S100 protein family with oxidative stress-related and anti-inflammatory role. The
      mechanisms of human alveolar type II (ATII) cell injury leading to emphysema
      pathophysiology are not completely understood. We wanted to determine whether
      S100A8 can protect ATII cells against injury induced by cigarette smoke and this
      disease development. We used freshly isolated ATII cells from non-smoker and
      smoker organ donors, as well as emphysema patients to determine S100A8 function.
      S100A8 protein and mRNA levels were low in individuals with this disease and
      correlated with its severity as determined by using lung tissue from areas with
      mild and severe emphysema obtained from the same patient. Its expression
      negatively correlated with high oxidative stress as observed by 4-HNE levels. We
      also detected decreased serine phosphorylation within S100A8 by PKAalpha in this
      disease. This correlated with increased S100A8 ubiquitination by SYVN1. Moreover,
      we cultured ATII cells isolated from non-smokers followed by treatment with
      cigarette smoke extract. We found that this exposure upregulated S100A8
      expression. We also confirmed the cytoprotective role of S100A8 against cell
      injury using the gain- and loss-of-function approaches in vitro. S100A8 knockdown
      sensitized cells to apoptosis induced by cigarette smoke. In contrast, S100A8
      overexpression rescued cell injury. Our results suggest that S100A8 protects ATII
      cells against injury and cigarette smoke-induced emphysema. Targeting S100A8 may
      provide a potential therapeutic strategy in this disease.

PMID- 30277796
TI  - Age-Specific Associations of Ozone and PM2.5 with Respiratory Emergency
      Department Visits in the US.
AB  - RATIONALE: While associations between air pollution and respiratory morbidity for
      adults 65 and older are well-documented in the United States, the evidence for
      people under 65 is less extensive. To address this gap, the Centers for Disease
      Control and Prevention's National Environmental Public Health Tracking Program
      collected respiratory emergency department (ED) data from 17 states. OBJECTIVES:
      Estimate age-specific acute effects of ozone and fine particulate matter (PM2.5)
      on respiratory ED visits. METHODS: We conducted time-series analyses in 894
      counties by linking daily respiratory ED visits with estimated ozone and PM2.5
      concentrations during the week before the date of the visit. Overall effect
      estimates were obtained using a Bayesian hierarchical model to combine county
      estimates for each pollutant by age group (children 0-18, adults 19-64, adults
      >=65, and all ages) and by outcome group (acute respiratory infection, asthma,
      chronic obstructive pulmonary disease, pneumonia, and all respiratory ED visits).
      MEASUREMENTS AND MAIN RESULTS: Rate ratios (95% credible interval) per 10 ug/m3
      increase in PM2.5 and all respiratory ED visits were 1.024 (1.018, 1.029) among
      children, 1.008 (1.004, 1.012) among adults <65, and 1.002 (0.996, 1.007) among
      adults 65 and older. Per 20 ppb increase in ozone, rate ratios were 1.017 (1.011,
      1.023) among children, 1.051 (1.046, 1.056) among adults <65, and 1.033 (1.026,
      1.040) among adults 65 and older. Associations varied in magnitude by age group
      for each outcome group. CONCLUSIONS: These results address a gap in the evidence
      used to ensure adequate public health protection under national air pollution
      policies.

PMID- 30277798
TI  - Evaluation of the Team Workload Questionnaire (TWLQ) in a Team-Choice Task.
AB  - OBJECTIVE: The present study was designed to evaluate the team workload
      questionnaire (TWLQ) in a task that was distinct from the task used to create it.
      BACKGROUND: The TWLQ was created from workload ratings generated by members of
      athletic sports teams. Given that such teams represent only a portion of the
      diversity of operational teams, we aimed to assess the generalizability of the
      TWLQ. METHOD: The present study applied the TWLQ in a collaborative choice task
      (hiring decision) to determine whether the factor structure reported in the
      initial publication of the scale would generalize from the execution tasks it was
      developed from to a disparate team task focused on consensus building. RESULTS:
      Confirmatory factor analysis indicated that the present data ( N = 144) were a
      poor fit for the three-factor structure of the TWLQ. Subsequent exploratory
      factor analysis revealed a much more interrelated model of team workload with no
      clear division between the three conceptual factors described in the original
      validation of the TWLQ. CONCLUSION: The factor structure of the TWLQ did not
      generalize to the present team-choice task. APPLICATION: Given that the duties of
      operational teams vary, it is critical that future research examine how the
      conceptual structure of team workload may be altered by task type.

PMID- 30277797
TI  - Leukocyte Telomere Length and Clinical Outcomes of Advanced Lung Adenocarcinoma
      Patients with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
      Treatment.
AB  - Gefitinib is currently one of the mostly used epidermal growth factor receptor
      tyrosine kinase inhibitors (EGFR-TKIs) recommended for treating nonsmall cell
      lung cancer. However, drug resistance is observed among the majority of patients
      after initial treatment. Factors that predict treatment prognosis and drug
      resistance to EGFR-TKIs remain elusive. The objective of this study is to
      investigate whether leukocyte relative telomere length (RTL) can be used as a
      prognostic biomarker of EGFR-TKIs therapy. In this study, 369 patients with stage
      IIIB or IV lung adenocarcinoma were recruited and treated with gefitinib as first
      line monotherapy. Leukocyte RTL of each patient was measured using quantitative
      polymerase chain reaction protocol and calculated according to Cawthon's formula.
      Finally, we examined the association between leukocyte RTL and prognosis or drug
      resistance of advanced lung adenocarcinoma to gefitinib treatment. Our results
      indicated that compared with long RTL, short leukocyte RTL was significantly
      associated with poor prognosis in all patients after gefitinib treatment (overall
      survival [OS]: 12.9 months vs. 17.8 months, p = 1.2 * 10-4; progression-free
      survival: 7.8 months vs. 13.0 months, p = 0.043). In addition, statistically
      significant association between short leukocyte RTL and short OS still existed
      among the EGFR mutant patients (hazards ratio [HR] = 1.65, 95% confidence
      interval [CI] = 1.28-2.12; p = 0.006). Besides EGFR mutation status, short RTL
      also contributed to remarkably elevated risk of gefitinib primary resistance (HR
      = 1.50, 95% CI = 1.05-2.15, p = 0.027). Our results highlight the clinical
      potential of leukocyte RTL as a novel biomarker in advanced lung adenocarcinoma
      treated with EGFR-TKIs.

PMID- 30277799
TI  - Dietary intake of anthocyanins and risk of cardiovascular disease: A systematic
      review and meta-analysis of prospective cohort studies.
AB  - Accumulating evidence suggests flavonoid intake is associated with reduced risk
      of non-communicable diseases. We aimed to systematically determine and quantify
      the potential association between dietary anthocyanin intake and risk of
      cardiovascular diseases (CVD). A systematic literature search of studies
      reporting anthocyanin intake and risk of fatal or nonfatal CVD was performed
      using SCOPUS, MEDLINE, CINAHL and Cochrane Library. The relative risk (RR) or
      hazard ratio (HR) of highest category of anthocyanin foods were pooled in a
      random-effects meta-analysis. Subgroup analysis were conducted to determine
      possible sources of heterogeneity. The meta-analysis suggested intake of dietary
      anthocyanins and reduced risk of CHD (RR = 0.91, 95% CI: 0.83, 0.99; I2 = 12.0,
      Ph = 0.337) and CVD mortality (RR = 0.92, 95% CI: 0.87, 0.97; I2 = 0.0, Ph =
      0.584). However, there was no relationship between the intake of these compounds
      and reduced risk of MI, stroke or total CVD. Subgroup analysis determined reduced
      risk of CHD and CVD mortality was more prominent for anthocyanidin intake, as
      opposed to anthocyanin or berries. Our systematic review and meta-analysis
      provides evidence that anthocyanins, specifically anthocyanidins, reduce the risk
      of CHD and CVD mortality. Further randomized controlled trials on anthocyanin
      intake and CVD risk factors are needed to support these findings.

PMID- 30277800
TI  - Consumption of sugar sweetened beverages and dietary fructose in relation to risk
      of gout and hyperuricemia: a systematic review and meta-analysis.
AB  - BACKGROUND: Findings on the association of sugar sweetened beverages (SSB) and
      fructose intakes with gout and hyperuricemia have been conflicting. OBJECTIVE: We
      aimed to perform a systematic review and meta-analysis on studies that examined
      the association of SSB and fructose consumption with gout and hyperuricemia in
      adults. METHODS: We searched PubMed, Scopus and Google Scholar up to Aug 2017 for
      all relevant published papers assessing SSB and fructose intakes and risk of gout
      and hyperuricemia. After excluding non-relevant papers, 10 studies remained in
      our systematic. Meta-analysis on SSB consumption and risk of gout was done on
      three effect sizes from cohort studies and five effect sizes from case-control
      studies. For risk of hyperuricemia, the meta-analysis was done on six effect
      sizes from cross-sectional studies. All analyses were performed on ORs or RRs.
      RESULTS: We found an overall significant positive association between SSB
      consumption and risk of gout in both cohort (summary effect size: 1.35; 95% CI:
      1.18-1.55) and case-control studies (summary effect size: 1.33; 95% CI: 1.06
      1.66). Meta-analysis on cross-sectional studies revealed that SSB consumption was
      associated with 35% greater odds of hyperuricemia (summary effect size: 1.35; 95%
      CI: 1.19-1.52). No evidence of between-study heterogeneity as well as publication
      bias was found. Although the studies on fructose intake and risk of gout and
      hyperuricemia were included in our systematic review, we did not perform met
      analysis on these studies due to insufficient number of publications. CONCLUSION:
      We found that SSB consumption was significantly associated with increased risk of
      gout and hyperuricemia in adult population. Further studies are needed to examine
      the association between dietary fructose intake and risk of gout and
      hyepruricemia.

PMID- 30277801
TI  - Promoter Haplotypes of the ABCB1 Gene Encoding the P-Glycoprotein Differentially
      Affect Its Promoter Activity by Altering Transcription Factor Binding.
AB  - Promoter single nucleotide polymorphisms (SNPs) of the ABCB1 gene, encoding the
      placental efflux transporter P-glycoprotein, can alter its expression and affect
      fetal exposure to therapeutics and environmental xenobiotics. SNPs are not
      arrayed as independent variants but as combinations forming defined haplotypes.
      Recently, we defined the haplotypes encompassing ABCB1 promoter SNPs and found
      that ABCB1 haplotypes differentially affect its promoter activity. The
      mechanism(s) by which ABCB1 haplotypes alter its promoter activity are not known.
      We hypothesize that the haplotype-dependent differences in ABCB1 promoter
      activity are due to haplotype-specific alterations in transcription factor (TF)
      binding. To test our hypothesis, we used a TF binding profile array and
      determined whether differences in TF binding exist across different ABCB1
      haplotypes. TFs showing significant haplotype binding differences were
      mechanistically evaluated using small interfering RNA (siRNA) in cultured human
      placental cells. Our data indicate significant haplotype-dependent differences in
      TF binding. Our siRNA studies showed that the regulatory effects of TFs on
      promoter activity are also haplotype dependent. Our data provide a mechanistic
      explanation for the differential effects of ABCB1 haplotypes on its promoter
      activity and underscore the importance of evaluating genetic variants in the
      context of haplotypes rather than individual SNPs when investigating their
      effects on gene/protein expression and disease risk.

PMID- 30277802
TI  - Prevalence and Characterization of Atypical Enteropathogenic Escherichia coli
      Isolated from Retail Foods in China.
AB  - Atypical enteropathogenic Escherichia coli (aEPEC) is an emerging pathogen that
      has been implicated in outbreaks of diarrhea worldwide. The objective of this
      study was to investigate the occurrence of aEPEC in retail foods at markets in
      the People's Republic of China and to characterize the isolates for virulence
      genes, intimin gene ( eae) subtypes, multilocus sequence types (STs), and
      antimicrobial susceptibility. From May 2014 to April 2015, 1,200 food samples
      were collected from retail markets in China, and 41 aEPEC isolates were detected
      in 2.75% (33 of 1,200) of the food samples. The virulence genes tir, katP, etpD,
      efa/lifA, ent, nleB, and nleE were commonly detected in these isolates. Nine eae
      subtypes were detected in the isolates, among which theta (23 isolates) and beta1
      (6 isolates) were the most prevalent. The 41 isolates were divided into 27 STs by
      multilocus sequence typing. ST752 and ST10 were the most prevalent. Antibiotic
      susceptibility testing revealed high resistance among isolates to streptomycin
      (87.80%), cephalothin (73.16%), ampicillin (51.22%), tetracycline (63.42%),
      trimethoprim-sulfamethoxazole (43.90%), and kanamycin (43.90%). Thirty isolates
      (73.17%) were resistant to at least three antibiotics, and 20 (53.66 %) were
      resistant to five or more antibiotics. Our results suggest that retail foods in
      markets are important sources of aEPEC. The presence of virulent and multidrug
      resistant aEPEC in retail foods poses a potential threat to consumers.
      Surveillance of aEPEC contamination and prudent use of antibiotics is strongly
      recommended in China.

PMID- 30277803
TI  - The success and the challenge of all-trans retinoic acid in the treatment of
      cancer.
AB  - All-trans retinoic acid (ATRA), an active metabolite of vitamin A, plays
      important roles in cell proliferation, cell differentiation, apoptosis, and
      embryonic development. The effects of ATRA are mediated by nuclear retinoid
      receptors as well as non-genomic signal pathway, such as MAPK and PKA. The great
      success of differentiation therapy with ATRA in acute promyelocytic leukemia
      (APL) not only improved the prognosis of APL but also spurred the studies of ATRA
      in the treatment of other tumors. Since the genetic and physiopathological
      simplicity of APL is not common in human malignancies, the combination of ATRA
      with other agents (chemotherapy, epigenetic modifiers, and arsenic trioxide, etc)
      had been extensively investigated in a variety of tumors. In this review, we will
      discuss in details about ATRA and its role in cancer treatment.

PMID- 30277804
TI  - Nitric Oxide Synthase 2 Induction Promotes Right Ventricular Fibrosis.
AB  - The ability of the right ventricle (RV) to compensate pressure overload is
      determining survival in pulmonary arterial hypertension (PAH). Nitric oxide (NO)
      reduces the RV afterload through pulmonary vasodilation, but excessive NO amounts
      cause oxidative stress. Oxidative stress drives remodeling of pulmonary arteries
      and the RV. Here, we hypothesized that NO synthase 2 (NOS2) induction leads to
      excessive NO amounts that contribute to oxidative stress and impairs RV adaption
      to PAH. We utilized a surgical pulmonary artery banding (PAB) mouse model where
      RV dysfunction and remodeling occur independent from changes in the pulmonary
      vasculature. Three weeks after PAB, NOS2 expression was increased 2-fold in the
      hypertrophied RV on transcript and protein level together with increased NO
      production. Histomorphology localized NOS2 in interstitial and perivascular
      cardiac fibroblasts (CFs) after PAB, confirmed by cell isolation experiments. In
      the hypertrophied RV, NOS2 induction was accompanied by an increased formation of
      reactive oxidants - blocked by ex vivo NOS inhibition. We show that reactive
      oxidant formation in the hypertrophied RV is in part NOS2-dependent (in NOS2
      deficient mice (NOS2-/-)). Lack of NOS2 induction prevented superoxide scavenging
      and decreased reactive oxidant formation. Functional measures of cardiac function
      by non-invasive echocardiography along with intra-cardiac catheterization
      revealed no differences in heart function between both genotypes after PAB.
      However, reduced NO and reactive oxidant formation in the hypertrophied RV of
      NOS2-/- mice was linked to reduced collagen accumulation through reduced collagen
      deposition from the cardiac fibroblast. Together, our data demonstrate a pro
      fibrotic role for NOS2 induction in the hypertrophied RV.

PMID- 30277805
TI  - Utilization of Chemical Deposition Technique for Preparation of Miniature 170Tm
      Sources and Preliminary Quality Assessment for Potential Use in Brachytherapy.
AB  - OBJECTIVE: This article describes the preparation of a 170Tm source by chemical
      deposition technique, its encapsulation in a titanium holder, and preliminary
      quality evaluation for potential utility as a brachytherapy source. METHODS: The
      procedure consisted of electrodeposition of Ni on a Cu wire followed by chemical
      deposition of 170Tm on it. Influence of feed solution pH, carrier Tm
      concentration, and reaction time were studied for optimum deposition of 170Tm on
      substrate. After sealing the source core in a titanium capsule, quality control
      tests were performed. Distribution of 170Tm on substrate was evaluated by
      autoradiography. Inactive Tm source was characterized by scanning electron
      microscope (SEM) and energy-dispersive X-ray (EDS) analyses. RESULTS: Under
      optimized conditions (pH 5, 10 MUg Tm carrier, 5 h), 170Tm source core could be
      prepared by deposition of >95% of 170Tm radioactivity on substrate. Swipe tests
      and immersion tests on encapsulated sources confirmed that removable
      radioactivity and radioactivity leakage levels were within stipulated limits.
      Autoradiography of 170Tm source confirmed uniformity of radioactivity
      distribution. While SEM analysis confirmed good adhesion of Tm on substrate, EDS
      analysis confirmed elemental constituents of the Tm-deposited substrate.
      CONCLUSION: The objective of preparing a 170Tm source by chemical deposition for
      potential brachytherapy applications could be successfully achieved.

PMID- 30277806
TI  - Understanding the biosyntheses and stress response mechanisms of aroma compounds
      in tea (Camellia sinensis) to safely and effectively improve tea aroma.
AB  - Metabolite formation is a biochemical and physiological feature of plants
      developed as an environmental response during the evolutionary process. These
      metabolites help defend plants against environmental stresses, but are also
      important quality components in crops. Utilizing the stress response to improve
      natural quality components in plants has attracted increasing research interest.
      Tea, which is processed by the tender shoots or leaves of tea plant (Camellia
      sinensis (L.) O. Kuntze), is the second most popular beverage worldwide after
      water. Aroma is an important factor affecting tea character and quality. The
      defense responses of tea leaves against various stresses during preharvest (tea
      growth process) and postharvest (tea manufacturing) processing can result in
      aroma formation. Herein, we summarize recent investigations into the biosyntheses
      of several characteristic aroma compounds prevalent in teas and derived from
      volatile fatty acid derivatives, terpenes, and phenylpropanoids/benzenoids.
      Several key aroma synthetic genes from tea leaves have been isolated, cloned,
      sequenced, and functionally characterized. Biotic stress (such as tea green
      leafhopper attack) and abiotic stress (such as light, temperature, and wounding)
      could enhance the expression of aroma synthetic genes, resulting in the abundant
      accumulation of characteristic aroma compounds in tea leaves. Understanding the
      specific relationships between characteristic aroma compounds and stresses is key
      to improving tea quality safely and effectively. [Formula: see text].

PMID- 30277807
TI  - Effects of a self-management programme on patient participation in patients with
      chronic heart failure or chronic obstructive pulmonary disease: A randomized
      controlled trial.
AB  - BACKGROUND: Self-management strategies are crucial to patients with long-term
      conditions and can presumably promote patient participation, given that to
      patients, patient participation connotes opportunities for self-care (along with
      being engaged in an exchange of knowledge, a phrasing of joint goals and planning
      of care). So far, limited attention has been given to what components support
      self-management and what outcomes can be achieved. An exclusive self-management
      programme in primary healthcare entailed assessing its influence on patient
      participation. AIM: To describe the effects of a self-management programme on
      preferences for, and experiences of, patient participation in patients with
      chronic obstructive pulmonary disease or chronic heart failure. METHODS: A
      randomized controlled trial with a six session intervention programme, including
      phrasing of individual action plans and group discussions on the patients'
      issues. The intervention group ( n=59) received standard care and the self
      management programme, and the control group ( n=59) received standard care only.
      Data was collected at baseline and at three months and 12 months after the
      intervention started, using the Patient Preferences for Patient Participation
      (the 4Ps) measure. RESULTS: No significant differences were found within the
      groups, or between the groups, in preferences and experiences of patient
      participation, either in summary score or at an item level. CONCLUSION: A self
      management group programme led by trained primary healthcare staff in primary
      care did not serve as means to influence patients' experience of patient
      participation in the care of their long-term condition. Further studies are
      needed in regard to what facilitates patient participation in this setting and
      beyond.

PMID- 30277808
TI  - Lactation Space Experiences and Preferences Among Health Care Workers in an
      Academic Medical Center.
AB  - BACKGROUND: Comprehensive workplace lactation support programs can reduce the
      risk for early breastfeeding discontinuation; however, scant evidence is
      available to inform user-centered design of employee lactation spaces. This study
      describes health care workers' preferences for lactation space. MATERIALS AND
      METHODS: In 2016-2017, a convenience sample of 151 women who pumped at work at an
      academic medical center reported on demographics, lactation experiences, and room
      and equipment preferences through an online survey. RESULTS: Respondents worked
      in research and administration (32%), were nurses (30%), physicians and medical
      students (19%), or allied health or clinical support staff (19%). Seventy percent
      had ever used one of the hospital's dedicated lactation spaces. Forty-nine
      percent ranked hospital-grade pumps the most important piece of lactation room
      equipment; 83% preferred multiple occupancy lactation suites; and the average
      maximum acceptable distance to lactation space was 5.6 minutes. CONCLUSIONS:
      Optimal lactation infrastructure supports the immediate and long-term health of
      female workers and their children. User needs and preferences can guide design of
      lactation space to ensure a minimum standard for design, equipment, and distance.
      Workers may have different preferences depending on roles and experiences; thus,
      a variety of solutions may be most effective.

PMID- 30277809
TI  - P-311 in Scar Wars: Myofibroblasts Lost without TGFbeta Translation.

PMID- 30277810
TI  - Recent advancements in the application of non-thermal plasma technology for the
      seafood industry.
AB  - Non-thermal plasma (NTP) is one of the most promising minimal processing methods
      for the food industry. However up until recently there are limited studies which
      would report the application and effect of NTP on processed seafood. The
      objective of this review is to highlight the recent findings and advancements in
      the application of NTP within the fish and other seafood industry, including
      direct application of fresh and dried fish and seafood with as well as indirect
      application of plasma activated water and seafood industry wastewater
      purification. The article also summarizes the effect of plasma treatment on
      microbiological quality, physicochemical and sensory properties and oxidation
      rate of treated fish and seafood. NTP has high potential to be used within
      various fields of seafood industry. It is especially effective in treatment of
      dried seafood products, but the use of plasma activated water during various
      processing steps such as seafood washing could be also beneficial. Moreover NTP
      could also be used as a cost effective and environmentally friendly method for
      seafood wastewater purification.

PMID- 30277811
TI  - The Antimicrobial Effect of a Commercial Mixture of Natural Antimicrobials
      Against Escherichia coli O157:H7.
AB  - Ruminants are important reservoirs of E. coli O157:H7 and are considered as the
      major source of most foodborne outbreaks (e.g., 2017 outbreak in Germany, 2014
      and 2016 outbreaks in United States, all linked to beef products). A promising
      strategy to reduce E. coli O157 is using antimicrobials to reduce the pathogen
      levels and/or virulence within the animal gastrointestinal tract and thus
      foodborne disease. The aim of the study was to determine the efficacy of a
      commercial mixture of natural antimicrobials against E. coli O157. The minimum
      inhibitory concentration and minimum bactericidal concentration of the
      antimicrobial were quantitatively determined and found to be 0.5% and 0.75% (v/v)
      of the natural antimicrobial, respectively. Microbial growth kinetics was also
      used to determine the effect of the antimicrobial on the pathogen. The natural
      antimicrobial affected the cell membrane of E. coli O157, as demonstrated by the
      increase in relative electric conductivity and increase in protein and nucleic
      acid release. The antimicrobial was also able to significantly reduce the
      concentration on E. coli O157 in a model rumen system. Biofilm assays showed that
      subinhibitory concentrations of the antimicrobial significantly reduced the E.
      coli 0157 biofilm forming capacity without influencing pathogen growth. In
      addition, the natural antimicrobial was able to reduce motility and
      exopolysaccharide production. Subinhibitory concentrations of the antimicrobial
      had no effect on AI-2 production. These findings suggest that the natural
      antimicrobial exerts an antimicrobial effect against E. coli O157 in vitro and in
      a model rumen system and could be potentially used to control this pathogen in
      the animal gut. The results also indicate that subinhibitory concentrations of
      the antimicrobial effectively reduce biofilm formation, motility, and
      exopolysaccharide production.

PMID- 30277812
TI  - Recommended Reading from the Galway University Hospitals, Department of
      Anaesthesia and Intensive Care Medicine Fellows.

PMID- 30277813
TI  - Genome-Wide DNA Methylation Profile of Gene cis-Acting Element Methylations in
      All-trans Retinoic Acid-Induced Mouse Cleft Palate.
AB  - DNA methylation epigenetically regulates gene expression. This study is aimed to
      investigate genome-wide DNA methylations involved in the regulation of palatal
      fusion in the all-trans retinoic acid-induced mouse cleft palate model. There
      were 4,718,556 differentially CCGG methylated sites and 367,504 CCWGG methylated
      sites for 1497 genes between case and control embryonic mouse palatal tissues.
      The enhancers (HDAC4 and SMAD3) and promoter (MID1) of these three genes had cis
      acting element methylation. HDAC4 is localized within the CCWGG, while MID1 and
      SMAD3 are localized within the CCGG of the gene intron. The methylation-specific
      polymerase chain reaction data confirmed the MethylRAD-seq results, while the
      quantitative reverse transcriptase-polymerase chain reaction result showed that
      changes in gene expression inversely were associated with the cis-acting element
      methylation of the gene during retinoic acid-induced palatal fusion. The GO and
      KEGG data showed that these three genes could regulate cell proliferation,
      skeletal muscle fiber development, and development-related gene signaling or
      activity. The cis-acting element methylation of HDAC4, SMAD3, and MID1 may play a
      regulatory role during palatal fusion. Further research is needed to verify these
      novel epigenetic biomarkers for cleft palate.

PMID- 30277814
TI  - HIV-Related Stigma by Healthcare Providers in the United States: A Systematic
      Review.
AB  - Reducing HIV-related stigma may enhance the quality of HIV prevention and care
      services and is a national prevention goal. The objective of this systematic
      review was to identify studies of HIV-related stigma among healthcare providers.
      For studies published between 2010 and 2017, we: (1) searched databases using our
      keywords, (2) excluded nonpeer reviewed studies, (3) limited the findings to the
      provider perspective and studies conducted in the United States, (4) extracted
      and summarized the data, and (5) conducted a contextual review to identify common
      themes. Of 619 studies retrieved, 6 were included, with 3 themes identified: (1)
      attitudes, beliefs, and behaviors (n = 6), (2) quality of patient care (n = 3),
      and (3) education and training (n = 2). Factors associated with HIV-related
      stigma varied by gender, race, provider category, and clinical setting. Providers
      with limited recent HIV-stigma training were more likely to exhibit stigmatizing
      behaviors toward patients. Developing provider-centered stigma-reduction
      interventions may help advance national HIV prevention and care goals.

PMID- 30277815
TI  - HIV Care and Viral Load Suppression After Sexual Health Clinic Visits by Out-of
      Care HIV-Positive Persons.
AB  - Outcomes among people living with HIV (PLWH) in New York City (NYC) remain
      suboptimal. To assess the potential role of the city's sexual health clinics
      (SHCs) in improving HIV outcomes and reducing HIV transmission, we examined HIV
      care status and its correlates among HIV-positive SHC patients in NYC. Clinic
      electronic medical records were merged with longitudinal NYC HIV surveillance
      data to identify HIV-positive patients and derive their retrospective and
      prospective HIV care status. Evidence of HIV care and viral load suppression
      (VLS) after clinic visit were considered outcomes. Logistic regression models
      were used to assess their correlates. A third of the 1045 PLWH who visited NYC
      SHCs in 2012 were out of HIV care (OOC) in the 12 months preceding the clinic
      visit, and were less likely than those previously in HIV care (IC) to have
      subsequent evidence of HIV care (42% vs. 72%) or VLS in the 12 months after the
      visit (39% vs. 76%). VLS was particularly low among patients diagnosed with >=2
      sexually transmitted infections (46%). The odds of VLS were lowest among those
      OOC before the clinic visit [versus those IC, adjusted odds ratio (aOR): 0.21,
      95% confidence interval (CI): 0.16-0.29], non-Hispanic blacks (versus non
      Hispanic whites, aOR: 0.58, 95% CI: 0.37-0.90), and residents of high-poverty
      neighborhoods (>30% vs. <10%, aOR: 0.51, 95% CI: 0.29-0.89). Our findings suggest
      that SHCs could serve as an intervention point to (re-)link PLWH to HIV care.
      Real-time provider alerts about patients' OOC status could help achieve that
      goal.

PMID- 30277816
TI  - Gender Differences in HIV Testing, Diagnosis, and Linkage to Care in Healthcare
      Settings: Identifying African American Women with HIV in Chicago.
AB  - Women account for 25% of all people living with HIV and 19% of new diagnoses in
      the United States. African American (AA) women are disproportionately affected.
      Yet, differences in the care continuum entry are not well understood between
      patient populations and healthcare sites. We aim to examine gender differences in
      diagnosis and linkage to care (LTC) in the Expanded HIV Testing and Linkage to
      Care (X-TLC) program within healthcare settings. Data were collected from 14
      sites on the South and West sides of Chicago. Multivariate logistic regression
      analysis was used to determine the differences in HIV diagnoses and LTC by gender
      and HIV status. From 2011 to 2016, X-TLC performed 281,017 HIV tests; 63.7% of
      those tested were women. Overall HIV seroprevalence was 0.57%, and nearly one
      third (29.4%) of HIV-positive patients identified were cisgender women. Of newly
      diagnosed HIV-positive women, 89% were AA. 58.5% of new diagnoses in women were
      made at acute care hospitals, with the remainder at community health centers.
      Women who were newly diagnosed had a higher baseline CD4 count at diagnosis
      compared with men. Overall, women had lower odds of LTC compared with men
      (adjusted odds ratio = 0.58, 95% confidence interval 0.44-0.78) when controlling
      for patient demographics and newly versus previously diagnosed HIV status. Thus,
      interventions that focus on optimizing entry into the care continuum for AA women
      need to be explored.

PMID- 30277817
TI  - Brain iron loading impairs DNA methylation and alters GABAergic function in mice.
AB  - Iron deficiency is closely associated with altered GABA metabolism and affective
      behavior. While mutation in the hemochromatosis ( HFE) gene disrupts iron
      homeostasis and promotes oxidative stress that increases the risk of
      neurodegeneration, it is largely unknown whether HFE mutation modifies GABAergic
      homeostasis and emotional behavior. The goal of our study was to investigate the
      impact of HFE on GABAergic neurochemistry and redox-epigenetic regulation in the
      brain using H67D HFE-mutant mice that recapitulates the H63D-HFE mutation in
      humans. H67D mice displayed elevated redox-active iron levels in the brain by 32%
      compared to age-matched wild-type mice. Moreover, the H67D brain had increased
      isoprostane and decreased glutathione, indicating elevated oxidative stress.
      Additionally, the H67D brain had decreased global methylation and attenuated DNA
      methyltransferase (DNMT) activity. Direct addition of iron to purified DNMT in
      vitro decreased enzyme activity in a concentration-dependent manner. Last, H67D
      mice exhibited decreased anxiety-like behavior, which was associated with
      increased expression of the GABAA receptor alpha2 subunits by 93%, and these
      changes were also observed in H67D mice fed a low-iron diet. Taken together, our
      results suggest a putative role of HFE in regulating labile iron status in the
      brain, and mutation in H67D perturbs redox-methylation status, contributing to
      GABAergic dysfunction.-Ye, Q., Trivedi, M., Zhang, Y., Bohlke, M., Alsulimani,
      H., Chang, J., Maher, T., Deth, R., Kim, J. Brain iron loading impairs DNA
      methylation and alters GABAergic function in mice.

PMID- 30277818
TI  - Long noncoding RNA Plnc1 controls adipocyte differentiation by regulating
      peroxisome proliferator-activated receptor gamma.
AB  - Detailed understanding of molecular mechanisms controlling adipogenesis is of
      great importance to identify new targets for treating obesity. Emerging evidence
      suggests that long noncoding RNAs (lncRNAs) may play a pivotal role in
      adipogenesis. Here, we have identified a novel lncRNA, Plnc1, which is
      transcribed from a position ~25,000 bp upstream of the peroxisome proliferator
      activated receptor gamma2 ( PPAR-gamma2) gene. Plnc1 is abundantly expressed in
      adipose tissue, and obese mice have higher Plnc1 expression in adipose tissue
      than nonobese mice. Plnc1 was induced in established adipogenic lines ST2, 3T3
      L1, and C3H10T1/2 as well as in bone marrow stromal cells (BMSCs) after
      adipogenic treatment. Plnc1 knockdown blocked differentiation of ST2 cells and
      BMSCs into mature adipocytes, along with the reduction of PPAR-gamma,
      CCAAT/enhancer binding protein-alpha, and adipocyte protein 2. Conversely,
      overexpression of Plnc1 promoted ST2 cells and BMSCs to fully differentiate.
      Mechanism studies revealed that Plnc1 could reduce the methylation level of CpG
      region in the PPAR-gamma2 promoter and enhance the transcriptional activity of
      the promoter and thereby increase PPAR-gamma2 transcription. Our study suggests
      that Plnc1 promotes adipogenic differentiation through controlling the key
      adipogenic transcription factor PPAR-gamma and highlights the potential of Plnc1
      as a target for new therapies to control metabolic disorders like obesity.-Zhu,
      E., Zhang, J., Li, Y., Yuan, H., Zhou, J., Wang, B. Long noncoding RNA Plnc1
      controls adipocyte differentiation by regulating peroxisome proliferator
      activated receptor gamma.

PMID- 30277819
TI  - Suppression of AMPK/aak-2 by NRF2/SKN-1 down-regulates autophagy during prolonged
      oxidative stress.
AB  - NF-E2-related factor 2 (NRF2) transcription factor has a fundamental role in cell
      homeostasis maintenance as one of the master regulators of oxidative and
      electrophilic stress responses. Previous studies have shown that a regulatory
      connection exists between NRF2 and autophagy during reactive oxygen species
      generated oxidative stress. The aim of the present study was to investigate how
      autophagy is turned off during prolonged oxidative stress, to avoid overeating
      and destruction of essential cellular components. AMPK is a key cellular energy
      sensor highly conserved in eukaryotic organisms, and it has an essential role in
      autophagy activation at various stress events. Here the role of human AMPK and
      its Caenorhabditis elegans counterpart AAK-2 was explored upon oxidative stress.
      We investigated the regulatory connection between NRF2 and AMPK during oxidative
      stress induced by tert-butyl hydroperoxide (TBHP) in HEK293T cells and C.
      elegans. Putative conserved NRF2/protein skinhead-1 binding sites were found in
      AMPK/aak-2 genes by in silico analysis and were later confirmed experimentally by
      using EMSA. After addition of TBHP, NRF2 and AMPK showed a quick activation; AMPK
      was later down-regulated, however, while NRF2 level remained high. Autophagosome
      formation and Unc-51-like autophagy activating kinase 1 phosphorylation were
      initially stimulated, but they returned to basal values after 4 h of TBHP
      treatment. The silencing of NRF2 resulted in a constant activation of AMPK
      leading to hyperactivation of autophagy during oxidative stress. We observed the
      same effects in C. elegans demonstrating the conservation of this self-defense
      mechanism to save cells from hyperactivated autophagy upon prolonged oxidative
      stress. We conclude that NRF2 negatively regulates autophagy through delayed down
      regulation of the expression of AMPK upon prolonged oxidative stress. This
      regulatory connection between NRF2 and AMPK may have an important role in
      understanding how autophagy is regulated in chronic human morbidities
      characterized by oxidative stress, such as neurodegenerative diseases, certain
      cancer types, and in metabolic diseases.-Kosztelnik, M., Kurucz, A., Papp, D.,
      Jones, E., Sigmond, T., Barna, J., Traka, M. H., Lorincz, T., Szarka, A.,
      Banhegyi, G., Vellai, T., Korcsmaros, T., Kapuy, O. Suppression of AMPK/aak-2 by
      NRF2/SKN-1 down-regulates autophagy during prolonged oxidative stress.

PMID- 30277820
TI  - Galectin-1 promotes choroidal neovascularization and subretinal fibrosis mediated
      via epithelial-mesenchymal transition.
AB  - VEGFA and TGF-beta are known major angiogenic and fibrogenic factors. Galectin-1,
      encoded by lectin, galactoside-binding, soluble ( LGALS) 1, has attracted growing
      attention for its facilitatory role in angiogenesis and fibrosis through its
      modification of VEGFA and TGF-beta receptor signaling pathways. We reveal
      galectin-1 involvement in the mouse model of laser-induced choroidal
      neovascularization (CNV) and subretinal fibrosis, both of which represent the
      pathogenesis of age-related macular degeneration (AMD). Neither deletion nor
      overexpression of Lgals1 affected physiologic retinal development or visual
      function. Galectin-1/ Lgals1 was upregulated by CNV induction, whereas deletion
      of Lgals1 suppressed CNV together with downstream molecules of VEGF receptor
      (VEGFR)2. Loss of Lgals1 also attenuated subretinal fibrosis, expression of
      epithelial-mesenchymal transition (EMT) markers including Snai1, and
      phosphorylation of SMAD family member 2. Supporting these in vivo findings,
      silencing of LGALS1 in human retinal pigment epithelial (RPE) cells inhibited TGF
      beta1-induced EMT-related molecules and cell motilities. Conversely,
      overexpression of Lgals1 enhanced CNV and subretinal fibrosis. Specimens from
      patients with AMD demonstrated colocalization of galectin-1 with VEGFR2 in
      neovascular endothelial cells and with phosphorylated SMAD2 in RPE cells. These
      results suggested a biologic significance of galectin-1 as a key promotor for
      both angiogenesis and fibrosis in eyes with AMD.-Wu, D., Kanda, A., Liu, Y.,
      Kase, S., Noda, K., Ishida, S. Galectin-1 promotes choroidal neovascularization
      and subretinal fibrosis mediated via epithelial-mesenchymal transition.

PMID- 30277822
TI  - TP and/or EP3 receptors mediate the vasoconstrictor and pressor responses of
      prostaglandin F2alpha in mice and/or humans.
AB  - The vasoconstrictor and/or pressor effects of prostaglandin (PG)F2alpha
      participate in the development of vascular pathologies and limit the clinical use
      of the agent. This study aimed to determine the receptor types responsible for
      the vasoconstrictor activity of PGF2alpha and whether they mediate the pressor
      response evoked by the prostanoid under in vivo conditions. Experiments were
      performed on genetically altered mice and/or on vessels from these mice or
      humans. Here we show that deletion of the thromboxane-prostanoid receptor (TP-/-)
      abolished or drastically diminished the contraction to PGF2alpha in isolated
      mouse vessels (some of which were resistance arteries) and reduced the elevation
      in blood pressure evoked by the prostanoid under in vivo conditions. In
      accordance, TP antagonism abolished the contraction in small arteries of human
      omentum. Further deletion of E prostanoid receptor type 3 (EP3-/-) removed the
      PGF2alpha-evoked contraction that remained in some TP-/- arteries and added to
      the effect of TP-/- on the elevation in blood pressure evoked by the prostanoid
      under in vivo conditions. In contrast, the uterine contraction to PGF2alpha
      mediated via the F prostanoid receptor (FP) was unaltered in TP-/-/EP3-/- mice.
      These results demonstrate that the non-FP receptors TP and/or EP3 mediate the
      vasoconstrictor and pressor effects of PGF2alpha, which are still of concern
      under clinical conditions.-Liu, B., Li, J., Yan, H., Tian, D., Li, H., Zhang, Y.,
      Guo, T., Wu, X., Luo, W., Zhou, Y. TP and/or EP3 receptors mediate the
      vasoconstrictor and pressor responses of prostaglandin F2alpha in mice and/or
      humans.

PMID- 30277821
TI  - Calorie restriction prevents diet-induced insulin resistance independently of PGC
      1-driven mitochondrial biogenesis in white adipose tissue.
AB  - Calorie restriction (CR) exerts remarkable, beneficial effects on glucose
      homeostasis by mechanisms that are not fully understood. Given the relevance of
      white adipose tissue (WAT) in glucose homeostasis, we aimed at identifying the
      main cellular processes regulated in WAT in response to CR in a pathologic
      context of obesity. For this, a gene-expression profiling study was first
      conducted in mice fed ad libitum or subjected to 40% CR. We found that the gene
      network related to mitochondria was the most highly upregulated in WAT by CR. To
      study the role that increased mitochondrial biogenesis plays on glucose
      homeostasis following CR, we generated a mouse model devoid of the coactivators
      peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1)alpha and
      PGC-1beta specifically in adipocytes. Our results show that mice lacking PGC-1s
      in adipocytes are unable to increase mitochondrial biogenesis in WAT upon CR.
      Despite a blunted induction of mitochondrial biogenesis in response to calorie
      deprivation, mice lacking adipose PGC-1s still respond to CR by improving their
      glucose homeostasis. Our study demonstrates that PGC-1 coactivators are major
      regulators of CR-induced mitochondrial biogenesis in WAT and that increased
      mitochondrial biogenesis and oxidative function in adipose tissue are not
      required for the improvement of glucose homeostasis mediated by CR.-Pardo, R.,
      Vila, M., Cervela, L., de Marco, M., Gama-Perez, P., Gonzalez-Franquesa, A.,
      Statuto, L., Vilallonga, R., Simo, R., Garcia-Roves, P. M., Villena, J. A.
      Calorie restriction prevents diet-induced insulin resistance independently of PGC
      1-driven mitochondrial biogenesis in white adipose tissue.

PMID- 30277823
TI  - The Forkhead Box C1, a Novel Negative Regulator of Osteogenesis, Plays a Crucial
      Role in Odontogenic Differentiation of Dental Pulp Stem Cells.
AB  - The forkhead box C1 (Foxc1) protein, a member of the forkhead/winged helix
      transcription factor family, is required in stem cell developmental processes.
      Recently, multiple studies have indicated the crucial role of Foxc1 in
      mesenchymal stem cell differentiation, but the precise effects and mechanisms on
      dental pulp stem cells (DPSCs) remain unclear. In this study, we evaluate the
      role of Foxc1 on the odontogenic differentiation and proliferation of DPSCs. Our
      results show that Foxc1 decreases time dependently in odontogenic differentiation
      of DPSCs. Meanwhile, overexpression of Foxc1 could significantly inhibit the
      mineralization of DPSCs and the expression of odontogenic-related genes, such as
      runt-related transcription factor 2 (Runx2), dentin sialophosphoprote (DSPP), and
      dentin matrix acidic phosphoprotein 1 (DMP-1). Foxc1 overexpression does not
      significantly alter the proliferation of DPSCs. In addition, Foxc1 reduces the
      expression of p-Smad1/5, an important modulator of bone morphogenetic protein
      (BMP)/Smad signaling pathway, inhibiting BMP/Smad signaling pathway. In
      conclusion, our data demonstrated that Foxc1 inhibits odontogenic differentiation
      of DPSCs and odontogenic-related gene expression through the BMP/Smad signaling
      pathway which may be useful for the dental regeneration and repair.

PMID- 30277824
TI  - Attempting to Convert Primed Porcine Embryonic Stem Cells into a Naive State
      Through the Overexpression of Reprogramming Factors.
AB  - Establishing pig embryonic stem cells (pESCs) remains a challenge due to
      differences in the genetic backgrounds of mouse, human, and pig. Therefore, pig
      specific pluripotency markers and cellular signaling must be identified. In this
      study, doxycycline (DOX)-inducible vectors carrying Oct4, sex-determining region
      Y-box 2 (Sox2), Nanog, Kruppel-like family 4 (Klf4), or Myc, which are known
      reprogramming factors, were transduced into pESCs. And pluripotency genes were
      analyzed in one or two reprogramming factor-expressed pESCs. When cultured
      without DOX, pESCs were stably maintained in basic fibroblast growth factor
      supplemented media. However, when treated with DOX, the cells lost their alkaline
      phosphatase (AP) activity and differentiated within 2 weeks. Subsequently, we
      investigated the expression of genes related to pluripotency in DOX-treated pESCs
      using quantitative reverse transcription-polymerase chain reaction (PCR).
      Expression levels of Oct4, E-cadherin, and Fut4 were significantly increased by
      Oct4 overexpression, and Oct4 and Fut4 were upregulated in the Sox2-infected
      group. When a combination of two reprogramming factors, including Oct4 or Sox2,
      was introduced, weak AP activity remained. In addition, several of the two
      reprogramming factor transduction groups could be maintained after subculturing
      with transgene activation. Although long-term culture failed, pESCs transduced
      with Oct4 and Nanog, Oct4 and Klf4, or Sox2 and Nanog combinations could be
      subcultured even under transgene activation conditions. Analysis of the cause of
      long-term culture failure by quantitative PCR confirmed that the expression of
      intermediate reprogramming markers was not maintained. Given these results,
      additional methods are needed to support the completion of each reprogramming
      phase to succeed in the conversion of the pluripotent state of pESCs. This study
      improves our understanding of pluripotent networks and can be used to aid in the
      establishment of bona fide pig pluripotent stem cells.

PMID- 30277825
TI  - What Can Cost-Effectiveness Analysis Tell Us About Chimeric Antigen Receptor T
      Cell Therapy for Relapsed Acute Lymphoblastic Leukemia?

PMID- 30277826
TI  - Improving Overall Survival in Older Adults With Acute Myeloid Leukemia:
      Subpopulations Matter.

PMID- 30277827
TI  - Working with Troubled Youth in Community, Mental Health and Justice Systems: The
      Mental Health Implications.

PMID- 30277828
TI  - Effects Of Brucellosis Serologic Status On Physiology and Behavior of Rocky
      Mountain Elk ( Cervus canadensis nelsoni) In Southwestern Montana.
AB  - Brucellosis, caused by bacteria in the genus Brucella, is an infectious zoonosis
      affecting animals and humans worldwide. Free-ranging Rocky Mountain elk ( Cervus
      canadensis nelsoni) and bison ( Bison bison) in the Greater Yellowstone Ecosystem
      (areas of southwestern Montana, eastern Idaho, and northwestern Wyoming, USA) are
      the self-sustaining reservoirs of bovine brucellosis ( Brucella abortus) and elk
      are considered the primary source of livestock infections. It has been
      hypothesized that Brucella-exposed elk might have different physiologic status
      (pregnancy rates and body condition) and migration behaviors than would healthy
      elk. Here we tested the effects of brucellosis serologic status on pregnancy
      rates and winter ingesta free body fat of 100 female elk in southwestern Montana.
      We also evaluated the effects of serologic status on two characteristics of
      spring migration behavior, migration types (migrant, mixed migrant, resident,
      disperser, nomad, and undetermined type) and timing (start and end dates and
      duration). The migration behaviors were quantified using a model-driven approach
      based on the relative net squared displacement. We detected a significant
      difference (P=0.003) in pregnancy rates between seropositive and seronegative
      elk, with about a 30% drop in seropositive individuals. However, we did not
      detect differences in body fat between seropositive and seronegative elk or
      differences in either migration type or timing of spring migration. These results
      confirmed that the major effect of brucellosis in free-ranging elk is associated
      with reproduction.

PMID- 30277829
TI  - Presumed Photoreceptor Dysplasias In Peregrine Falcons ( Falco peregrinus) and
      Peregrine Falcon Hybrids.
AB  - We describe a case series of photoreceptor dysplasia with secondary retinal
      degeneration in juvenile peregrine falcons. Six Peregrine Falcons ( Falco
      peregrinus) and three Peregrine Falcon * Prairie Falcon ( Falco mexicanus)
      hybrids had early-life visual deficits. Eight birds had visual defects shortly
      after hatching, and one bird had visual deficits first noticed at 5 mo of age.
      Complete ophthalmic examinations were performed in each animal. Eight of the
      animals had electroretinograms, and nine of the animals had their eyes examined
      histologically after euthanasia. Ophthalmic examinations did not reveal
      consistent and potentially blinding abnormalities, including an absence of
      ophthalmoscopic retinal lesions. Electroretinographic findings included subnormal
      amplitudes (with rod responses more abnormal than cone responses), with a
      negative b-wave amplitude occurring in one bird. Histologically, a reduction in
      the number of photoreceptors was present with numerous degenerative changes to
      the remaining photoreceptors, including frequent blunting and disorganization of
      photoreceptor outer segments, decreased numbers of cells in the inner nuclear
      layer, decreased numbers of ganglion cells, decreased thickness of the nerve
      fiber layer, and decreased myelinated axons within the optic nerve.
      Ultrastructurally, only minor cone outer segment changes and occasional
      phagocytic cells were seen. Results strongly suggested a primary retinopathy,
      characterized by photoreceptor dysplasia and secondary retinal degeneration with
      loss of cellular elements throughout the retina. The presence of a similar
      spectrum of findings in related individuals, the early age of onset, and the
      relative lack of other environmental, ocular, or systemic abnormalities suggested
      possible heritability.

PMID- 30277830
TI  - First Report of Extended-Spectrum Betalactamase-Producing Klebsiella pneumoniae
      Among Fecal Carriage in Iran: High Diversity of Clonal Relatedness and Virulence
      Factor Profiles.
AB  - Increasing rate of silent intestinal carriers with extended-spectrum
      betalactamase (ESBL)-producing Klebsiella pneumonia (ESBL-KP) has given rise to a
      serious healthcare problem in clinical settings. Various epidemiological studies
      are being conducted to determine clonal relatedness among carriers. In this
      study, we investigated the intestinal carriage of ESBL-KP and clonal relatedness
      among ESBL-KP isolated from fecal carriage in Iran for the first time. A total of
      120 rectal swabs (RSs) were collected including 61 from inpatients of intensive
      care unit and 59 from outpatients. ESBL-KP screening was performed using
      MacConkey agar supplemented with cefotaxime. PCR was done for detection of ESBL,
      carbapenemase, and virulence factor genes. Conjugation experiments and PCR-based
      replicon typing were performed. Clonal relatedness was investigated by multilocus
      sequence typing (MLST) and multiple locus variable number tandem repeat analysis
      (MLVA). Out of a total of 120 RSs, 18.3% (22/120) ESBL-KP were isolated. The rate
      of blaCTXM-15 was 81%. ompk35 was the most prevalent virulence gene detected in
      86.3% of the isolates. In conjugation experiments, three out of five tested
      isolates had conjugative plasmids. The most prevalent plasmid types belonged to
      IncL/M, IncA/C, and Inc FII. The MLST analysis showed that the main sequence
      types (STs) identified among ESBL-KP isolates were ST147, ST15, and ST16. The
      isolates were characterized into 4 miniclusters and 11 singletons using MLVA.
      High heterogeneity among ESBL-KP isolates indicated that this bacterium could be
      colonized in different sites and easily transferred. Screening of carriers in
      hospitals and community could help in controlling of infection in the healthcare
      and community settings.

PMID- 30277831
TI  - The effect of antigen dose on T cell-targeting vaccine outcome.
AB  - During the past 3-4 decades, an increasing amount of evidence has pointed to the
      complex role of the antigen dose or T cell receptor (TCR) stimulation strength on
      the subsequent type, duration and "flavor" or quality of the response. Antigen
      dose was initially shown to impact Th1/Th2 bias, and later also shown to
      differentially affect development and induction of Tregs, Th17, T-follicular
      helper (Tfh), cells, and others. In recent years the quality of both CD4/8 T
      cells during infections, cancer and/or autoimmunity has turned out to be critical
      for subsequent disease outcome. Importantly, different vaccination strategies
      also lead to different types of T cell responses, and the role of the antigen
      dose is emerging as an important factor as well as a tool for investigators to
      utilize in fine-tuning vaccine efficacy. This commentary will highlight essential
      background of how antigen dose can impact and affect the quality of T cell
      responses, and discuss how this translates in different vaccine settings.

PMID- 30277832
TI  - Trypanosoma cruzi in a Mexican Free-Tailed Bat ( Tadarida brasiliensis) in
      Oklahoma, USA.
AB  - Trypanosoma cruzi is a vector-borne protozoan parasite that infects seven million
      individuals in Central and South America and is the etiologic agent of Chagas
      disease. There are increasing reports of endemic transmission within the southern
      US. Trypanosoma cruzi occurs in wild raccoons and dogs in Oklahoma, but its
      endemicity in the state is poorly studied. We suspected Mexican free-tailed bats
      ( Tadarida brasiliensis) contributed to the endemicity of T. cruzi in Oklahoma
      due to their annual migration from Central America to their North American
      maternity roosts. During the summer of 2017, we sampled 361 Mexican free-tailed
      bats for T. cruzi at three maternity roosts in Oklahoma. We collected wing
      tissues, extracted T. cruzi DNA, amplified target DNA by PCR using the primers
      TCZ1/TCZ2, and observed amplification by gel electrophoresis. One juvenile
      Mexican free-tailed bat was positive for T. cruzi resulting in a 0.27% prevalence
      in the 361 sampled bats. Our finding of a wild bat naturally infected with T.
      cruzi in Oklahoma provided insight on the endemicity of T. cruzi in
      underrepresented endemic areas. The positive sample was sequenced, confirmed as
      T. cruzi, and uploaded to GenBank (MG869732). Future research will focus on
      monitoring T. cruzi prevalence in wild bats and insect vectors to better
      understand the enzootic emergence of this neglected tropical parasite.

PMID- 30277833
TI  - Affinity of Staphylococcal A and Streptococcal G Proteins to West Indian Manatee
      ( Trichechus manatus manatus) Immunoglobulins.
AB  - The West Indian manatee ( Trichechus manatus manatus), a subspecies that inhabits
      coastal areas of Central and South America, has been listed as a vulnerable
      species because of the rapid decline in its population. Commercially available
      immunologic reagents specific for sirenians are lacking, limiting the development
      of sensitive immunodiagnostic assays. We observed the affinity of the microbial
      proteins A and G to T. m. manatus immunoglobulins. Manatee serum pools were
      analyzed using enzyme-linked immunosorbent assay (ELISA) to determine the
      affinity intensity followed by western blotting to confirm the specific binding
      of proteins A and G to immunoglobulins. The ELISA demonstrated maximum affinity
      of both proteins until the serum dilution of 1:12,800, with a similar affinity
      for both proteins. Because both A and G proteins exhibited affinity to manatee
      immunoglobulins, they can be used to develop sensitive immunodiagnostic assays
      for this species, contributing to manatee conversation procedures.

PMID- 30277834
TI  - Hyperimmune bovine colostrum reduces gastrointestinal carriage of uropathogenic
      Escherichia coli.
AB  - Debilitating recurrent urinary tract infections (UTIs) are often associated with
      gastrointestinal colonisation by uropathogens, such as uropathogenic Escherichia
      coli (UPEC), suggesting that these populations might be a suitable target for the
      treatment and prevention of recurrent UTI. However, antimicrobial treatment is
      generally unable to prevent recurrent UTI, and often selects for multidrug
      resistant uropathogens in the gut, and causes dysbiosis of the gut, vaginal, and
      urinary microbiota. Of note, the globally-disseminated multi drug resistant UPEC
      lineage, ST131, is known to both persistently colonise the gut and the urinary
      tract, and is associated with antibiotic treatment failure, indicating the need
      for novel non-antibiotic therapeutics for the treatment of UTI. This study
      therefore presents hyperimmune bovine colostrum (HBC) as a suitable therapy for
      the treatment of UPEC gastrointestinal colonisation. This work demonstrates that
      the vaccination of pregnant cows with inactivated cells from a ST131 UPEC isolate
      results in a highly specific anti-UPEC HBC, and that this product is able to
      disrupt the gastrointestinal colonisation of ST131 UPEC in mice.

PMID- 30277835
TI  - Optimizing cancer immunotherapy: Is it time for personalized predictive
      biomarkers?
AB  - Cancer immunotherapy, a treatment that selectively augments a patient's anti
      tumor immune response, is a breakthrough advancement in personalized medicine. A
      subset of cancer patients undergoing immunotherapy have displayed robust and long
      lasting therapeutic responses. Currently, the spotlight is on the use of blocking
      antibodies against the T-cell checkpoint molecules, cytotoxic T-lymphocyte
      associated antigen 4 (CTLA-4) and programed cell death-1 (PD-1)/programed death
      ligand 1 (PD-L1), which have been effectively used to combat many cancers types.
      Despite the overall enthusiasm, immune checkpoint blockade inhibitors suffer from
      significant limitations such as high cost, serious toxicity in a substantial
      proportion of patients, and a response rate as low as 10%-40% in some clinical
      trials. Consequently, there is an urgent and unmet medical need for companion
      biomarkers that could both predict the response of individual patients to these
      therapies, and provide the means for precise monitoring of their therapeutic
      outcome. In this era of precision medicine, predictive biomarkers are a hot
      commodity because they can effectively separate responders from non-responders,
      and spare non-responders from serious therapy-related toxicity. Emerging
      predictive biomarkers for immune checkpoint blockade are: PD-L1 expression,
      increased amounts of tumor-infiltrating lymphocytes, increased mutational load
      and mismatch repair deficiency. Other well-studied biomarkers include
      inflammatory infiltrate, absolute lymphocyte count and lactate dehydrogenase
      levels. We review recent progress on predictive cancer biomarkers in
      immunotherapy, with a special emphasis on serum autoantibodies that have the
      potential to be personalized for optimal clinical outcomes.

PMID- 30277836
TI  - Sorafenib inhibits caspase-1 expression through suppressing TLR4/stat3/SUMO1
      pathway in hepatocellular carcinoma.
AB  - Sorafenib has been demonstrated to be a beneficial treatment for advanced
      hepatocellular carcinoma (HCC). Emerging evidence indicates that caspase-1
      activation plays a crucial role in HCC progression. However, the relationship
      between caspase-1 and sorafenib has rarely been reported. In this study, we
      showed that caspase-1 was essential for lipopolysaccharide (LPS)-induced
      epithelial-mesenchymal transition (EMT). Moreover, sorafenib treatment could
      inhibit LPS-stimulated caspase-1 overexpression through restricting the nuclear
      transport of p65, which contributed to inactivation of NF-kappaB. Co
      immunoprecipitation (Co-IP) experiments and immunoblot analysis indicated that
      sorafenib treatment decreased the SUMOylation of p65 via inhibiting
      TLR4/stat3/SUMO1 signaling cascades. In conclusion, the results of this study
      suggest that sorafenib inhibits caspase-1 expression through suppressing the
      nuclear translocation of p65 and provide new insights into the mechanisms of
      sorafenib treatment in HCC.

PMID- 30277837
TI  - Maoberry (Antidesma bunius) Improves Glucose Metabolism, Triglyceride Levels, and
      Splenic Lesions in High-Fat Diet-Induced Hypercholesterolemic Rats.
AB  - Excessive consumption of a high-fat diet (HFD) is associated with
      hypercholesterolemia and cardiovascular disease (CVD). Dark purple maoberry
      (Antidesma bunius) fruit is a very good source of antioxidants. We investigated
      the effects of maoberry on immune function, lipid profiles, and oxidative stress
      in HFD-induced hypercholesterolemia. Seventy-two male Sprague Dawley rats were
      divided into the normal group fed with standard diet (ND); HFD groups (HF); and
      low, medium, and high dose of maoberry extract groups and a simvastatin group (HF
      L, HF-M, HF-H, and HF-S, respectively). Maoberry groups were given maoberry
      extract at concentrations of 0.38, 0.76, and 1.52 g/kg per day. At the same time,
      HF-S groups were administered simvastatin 10 mg/kg per day. After 12 weeks of
      maoberry treatment, significant reductions in body weight and triglyceride levels
      were observed in HF-L, HF-M, and HF-H groups in comparison with HF groups (P <
      .05). Obvious negative changes in spleen histology were found in HF groups, but
      not in maoberry-treated groups. Modest, but not significant, improvements were
      observed in other lipid profiles, immune cells in peripheral blood, oxidative
      stress, and antioxidant capacity after maoberry supplementation. In summary,
      these findings suggest that maoberry was helpful in reducing atherogenic risk
      factors such as lipid profiles, especially triglyceride, inflammation, oxidative
      stress related to CVD, and lesions in spleen histopathology.

PMID- 30277838
TI  - Laparoscopically Assisted Anorectoplasty for Intermediate-Type Imperforate Anus:
      Comparison of Surgical Outcomes with the Sacroperineal Approach.
AB  - AIM: This study aimed to compare the surgical outcomes of patients with the
      intermediate-type imperforate anus who underwent laparoscopically assisted
      anorectoplasty (LAARP; L group) with those of patients who underwent
      sacroperineal anorectoplasty (S group). MATERIALS AND METHODS: The medical
      records of patients with intermediate-type imperforate anus at a single
      institution between April 1983 and April 2017 were retrospectively reviewed.
      Fecal continence was evaluated using the clinical assessment score for fecal
      continence developed by the Japanese Study Group of Anorectal Anomalies (maximum
      score, 8). RESULTS: Twelve cases (rectobulbar urethral fistula, 7; anal agenesis
      without fistula, 4; and rectovaginal fistula, 1) were included in the L group
      versus 14 cases (rectobulbar urethral fistula, 11, and anal agenesis without
      fistula, 3) in the S group. Age and body weight at the time of surgery and rate
      of associated anomalies did not differ significantly between the two groups. The
      total scores for fecal continence 3, 5, and 7 years after anorectoplasty were 4,
      5, and 4 points in the L group and 4, 5, and 6 points in the S group,
      respectively, showing no significant intergroup differences. Mucosal prolapse
      occurred in 50% of the L group and 29% of the S group (P = .42), but failed
      rectocutaneous anastomosis and anal stenosis were not identified in either group.
      CONCLUSIONS: Postoperative fecal continence and the incidence of complications
      after LAARP were comparable with those after sacroperineal anorectoplasty in
      patients with intermediate-type imperforate anus.

PMID- 30277839
TI  - Loss of lipid phosphatase SHIP1 promotes macrophage differentiation through
      suppression of dendritic cell differentiation.
AB  - SH2-containing inositol 5'-phosphatase-1 (SHIP1) deficiency in mice results in
      abnormal myeloid expansion, and proinflammatory conditions in the lung. However,
      the mechanisms involved in SHIP1-mediated regulation of myeloid differentiation
      remain unclear. Here we show that SHIP1 is a key regulator of early
      differentiation for dendritic cells (DCs). We also provide critical evidence to
      modify the function of SHIP1 in in vitro development of BMDCs using the recent
      framework of defining DCs. We found that loss of SHIP1 suppresses GM-CSF-induced
      formation of bone marrow-derived DC (BMDC) colonies, leading to reduced BMDC
      number in BM cell culture. The number of maturated BMDCs decreased in SHIP1-KO
      culture, due to reduction of immature BMDCs, suggesting SHIP1 is critical for
      lineage commitment rather than for maturation from myeloid precursors to DCs. We
      further showed that F4/80+/MHCIIlow BM macrophage-like cells (BMMs) were the main
      population of SHIP1-KO BM culture. Treatment of wild-type BM culture with 3 alpha
      aminocholestane (3AC), a specific inhibitor for functional activity of SHIP1,
      caused a similar developmental defect in BMDCs as seen in SHIP1-KO cells,
      resulting in the absence of BMDC colony, and increased number of BMMs in BM
      culture. In conclusion, our results suggest that differentiation of BMDCs are
      markedly impaired under SHIP1 deficient condition, which causes skewed
      development of myeloid lineage cells manifested as pathological conditions
      associated with an excess of macrophage population.

PMID- 30277840
TI  - Efflux Pump Inhibitors, Alpha-Tocopherol and Aspirin: Role in Campylobacter
      jejuni and Campylobacter coli Fluoroquinolone Resistance.
AB  - This study aimed to investigate how efflux pump activity contributes to high
      fluoroquinolone (FQ) resistance in Campylobacter jejuni and Campylobacter coli
      isolates and to evaluate the modulatory effects of alpha-tocopherol and aspirin
      on FQ phenotypic resistance profiles. Minimum inhibitory concentration (MIC)
      values were obtained for different FQ agents following exposure to different
      efflux pump inhibitors (EPIs), including PabetaN (50 MUg/mL), which targets the
      cmeABC efflux system, and chlorpromazine (45 MUg/mL) and verapamil (120 MUg/mL),
      which target the MFS efflux system. The modulatory effects of aspirin (100 and
      200 MUg/mL) and alpha-tocopherol (4 and 10 MUg/mL) on FQ resistance profiles were
      examined. PabetaN had no effect on the MIC values of all FQ agents, while MFS
      efflux system inhibitors reduced the resistance level of different FQ agents and
      achieved an effect nearly comparable with that of alpha-tocopherol (10 MUg/mL).
      Aspirin exerted a dose-dependent excitatory effect on phenotypic resistance
      profiles, and this may raise concerns about its usage in both veterinary and
      clinical settings. While an efflux system other than cmeABC may play a role in FQ
      resistance in Campylobacter species, lipophilic substances may represent a new
      approach for controlling efflux pump activities.

PMID- 30277842
TI  - Correlates of Perinatal Post-Traumatic Stress Among Culturally Diverse Women with
      Depressive Symptomatology.
AB  - Post-traumatic stress disorder (PTSD) is an important and often neglected
      comorbidity of pregnancy; left untreated, it can lead to serious health
      complications for the mother and developing fetus. Structured interviews were
      conducted to identify risk factors of PTSD among culturally diverse women with
      depressive symptomatology receiving perinatal services at community
      obstetric/gynecologic clinics. Women abused as adults, with two or more instances
      of trauma, greater trauma severity, insomnia, and low social support were more
      likely to present perinatal PTSD symptoms. Perinatal PTSD is prevalent and has
      the potential for chronicity. It is imperative healthcare providers recognize
      salient risk factors and integrate culturally sensitive screening, appropriate
      referral, and treatment services for perinatal PTSD.

PMID- 30277841
TI  - Assessment of CEP55, PLK1 and FOXM1 expression in patients with bladder cancer in
      comparison with healthy individuals.
AB  - This case/control study is aimed at investigating the expression of CEP55, PLK1
      and FOXM1 in bladder cancer tissues and comparing it with healthy tissue and
      their relationship with clinicopathological features of BC. Total RNA was
      extracted; then, gene expression was performed using real-time PCR relative to 18
      s rRNA. 2-DeltaDeltaCT method was used to calculate the relative expression of
      genes. A significant over expression of FOXM1, PLK1 and CEP55 was observed in
      tumor samples compared to adjacent and normal bladder tissues (all p = 0.001).
      Therefore, they may be supposed as potential candidate's biomarkers for early
      diagnosis and targets for cancer therapy.

PMID- 30277843
TI  - Genome-Wide Association Studies for Spot Blotch (Cochliobolus sativus) Resistance
      in Bread Wheat Using Genotyping-by-Sequencing.
AB  - Spot blotch is a severe biotic menace of wheat caused by Cochliobolus sativus
      (syn. Bipolaris sorokiniana). Spot blotch is liable to major yield losses in warm
      humid regions. A genome-wide association study using genotyping-by-sequencing
      (GBS) markers was conducted to identify genomic regions associated with spot
      blotch resistance in a diversity panel of 159 spring wheat genotypes. In total,
      87,096 GBS markers covering the whole genome, with an average polymorphism
      information content value of 0.276, were applied. Linkage disequilibrium (LD)
      analysis indicated that the LD decay extent was approximately 100 Mbp. The panel
      was evaluated for disease severity (DS) and area under disease progress curve
      (AUDPC) for 2 years. In total, 24 marker-trait associations (MTA) were identified
      for DS and AUDPC of spot blotch, with 11 on chromosome 5B, 3 on 3A, 2 on 6B, and
      1 each on 1A, 2A, 1D, 2D, 4B, 5A, 7A, and 7B. A marker on chromosome 7B
      significantly explained 14% of the phenotypic variation of spot blotch severity
      as well as 11% of AUDPC. Five markers-three on chromosome 5B, one on 3A, and one
      on 7B-were associated with both DS and AUDPC with R2 ranging from 8 to 12%.
      Significant MTA can be utilized to develop wheat germplasm with resistance to
      spot blotch.

PMID- 30277844
TI  - Rapid, automated characterization of disulfide bond scrambling and IgG2 isoform
      determination.
AB  - Human antibodies of the IgG2 subclass exhibit complex inter-chain disulfide
      bonding patterns that result in three structures, namely A, A/B, and B. In
      therapeutic applications, the distribution of disulfide isoforms is a critical
      product quality attribute because each configuration affects higher order
      structure, stability, isoelectric point, and antigen binding. The current
      standard for quantification of IgG2 disulfide isoform distribution is based on
      chromatographic or electrophoretic techniques that require additional
      characterization using mass spectrometry (MS)-based methods to confirm disulfide
      linkages. Detailed characterization of the IgG2 disulfide linkages often involve
      MS/MS approaches that include electrospray ionization or electron-transfer
      dissociation, and method optimization is often cumbersome due to the large size
      and heterogeneity of the disulfide-bonded peptides. As reported here, we
      developed a rapid LC-MALDI-TOF/TOF workflow that can both identify the IgG2
      disulfide linkages and provide a semi-quantitative assessment of the distribution
      of the disulfide isoforms. We established signature disulfide-bonded IgG2 hinge
      peptides that correspond to the A, A/B, and B disulfide isoforms and can be
      applied to the fast classification of IgG2 isoforms in heterogeneous mixtures.

PMID- 30277846
TI  - Sphingolipids and Innate Immunity: A New Approach to Infection in the Post
      Antibiotic Era?
AB  - Antibiotic resistance has been demonstrated during the entire duration of
      antibiotic use even before medical utilization. Increasing resistance within
      virtually all microbes continues to be a problem. Infection with antibiotic
      resistant microbes has demonstrated significantly increased morbidity, death, and
      health-care-associated costs. Given increasing antibiotic resistance, multiple
      novel agents and approaches are being investigated, including antimicrobial
      lipids. Sphingosine and ceramide have been demonstrated to play a pivotal role in
      the innate immunity of the epidermis, oral mucosa, and respiratory epithelium;
      their role is being investigated currently in uroepithelium. Ceramide has been
      shown to be pivotal in the regulation of mammalian defense against Pseudomonas
      aeruginosa and Staphylococcus aureus pathogens commonly encountered in pneumonia.
      On the other hand, sphingosine appears to be equally pivotal and directly
      involved in pathogenic defense and has been demonstrated to "rescue" mammals from
      P. aeruginosa infections. Within this review, we will discuss the role of
      sphingolipids within innate immunity, pathogen invasion, and bacterial infection.
      We will discuss the antimicrobial activity of sphingosine and possibility for
      commercial use as an antimicrobial in the post-antibiotic era.

PMID- 30277845
TI  - Healthcare utilization following spinal cord injury: Objective findings from a
      regional hospital registry.
AB  - OBJECTIVE: The purpose was to describe the prevalence and characteristics of
      healthcare utilization among individuals with spinal cord injury (SCI) from a
      Level I trauma center. DESIGN: Retrospective data analysis utilizing a local
      acute trauma registry for initial hospitalization and merged with the Dallas-Fort
      Worth Hospital Council registry to obtain subsequent health care utilization in
      the first post-injury year. SETTING: Dallas, TX, USA. PARTICIPANTS: Six hundred
      and sixty four patients were admitted with an acute traumatic SCI from January
      2003 through June 2014 to a Level I trauma center. Fifty five patients that
      expired during initial hospitalization and 18 patients with unspecified SCI
      (defined by ICD-9 with no etiology or level of injury specified) were not
      included in the analysis, leaving a final sample of 591. OUTCOME MEASURES: Data
      included demographic and clinical characteristics, charges, and healthcare
      utilization. RESULTS: Mean age was 46.1 years (+/-18.9 years), the majority of
      patients were male (74%), and Caucasian (58%). Of the 591 patients, 345 (58%) had
      additional inpatient or emergency healthcare utilization accounting for 769
      additional visits (median of 3 visits per person). Of the 769 encounters, 534
      (69%) were inpatient and 235 (31%) were emergency visits not resulting in an
      admission. The most prevalent ICD-9 codes listed were pressure ulcer, neurogenic
      bowel, neurogenic bladder, urinary tract infection, fluid electrolyte imbalance,
      hypertension, and tobacco use. CONCLUSION: Individuals with SCI experience high
      levels of healthcare utilization which are costly and may be preventable.
      Increasing our understanding of the prevalence and causes for healthcare
      utilization after acute SCI is important to target preventive strategies.

PMID- 30277847
TI  - Micro-architecture study of the normal odontoid with micro-computed tomography.
AB  - INTRODUCTION: Odontoid fractures easily lead to instability, causing spinal cord
      injury. The aim of this study was to measure and analyze the micro-architecture
      and morphometric parameters of the normal odontoid with high-resolution three
      dimensional (3D) micro-computed tomography (micro-CT). METHODS: Micro-CT scans
      were obtained from five normal odontoid processes. The scanned data were
      reconstructed with micro-CT software, and the nutrient foramina and the
      ossification center of the base of the odontoid were revealed. The trabeculae of
      the odontoid were measured and divided into four parts to obtain the volume
      fraction of regions of interest. RESULTS: High-resolution 3D images of the micro
      structures' parameters were obtained from the odontoid using micro-CT software.
      The images demonstrated sponge-like trabecular bone, with the trabeculae showing
      a complex, net-like micro-construction. The subchondral bone plate was of lamella
      like, compact construction and extended and transformed into a net-like structure
      with rod-shaped trabeculae arranged radially in all directions. There was a
      statistically significant difference in the volume fraction compared with the
      region of interest in the fourth part of the trabeculae and the first part of the
      odontoid (P < 0.05). The nutrient foramina and the ossification center of the
      odontoid were also observed. CONCLUSIONS: It is feasible to use high-resolution
      3D micro-CT to evaluate the micro-architecture of the normal odontoid. Other
      studies can benefit from use of the micro-CT images, such as finite element
      evaluations.

PMID- 30277848
TI  - Nux Vomica Exposure Triggered Liver Injury and Metabolic Disturbance in Zebrafish
      Larvae.
AB  - Zebrafish larvae were used to further understand the liver toxicity of nux
      vomica. The histopathology, protein expression, and gene expression were assessed
      to confirm apoptosis in the liver, and then, profiles of the metabolites in
      zebrafish were investigated by untargeted metabolomic assessment to understand
      the potential toxicity mechanism of nux vomica. Histopathological observations
      showed that nux vomica caused damage to liver cells. Western blot results
      indicated increased expression of activated caspase3, and the result of real-time
      polymerase chain reaction showed a significant increase in the expression level
      of caspase-3, caspase-8, and caspase-9 genes (p < 0.05) compared with the control
      group. The liver injury from nux vomica was linked to the downregulation of amino
      acid (e.g., proline and alanine) and fatty acid (e.g., palmitoleic acid)
      metabolism and upregulation of some other fatty acid (e.g., arachidic acid) and
      purine (e.g., xanthine and uric acid) metabolism. The hepatotoxicity of nux
      vomica resulted from metabolic pathway disturbances, including small molecules
      involved in energy, purine, lipids, and amino acid metabolism.

PMID- 30277849
TI  - Overnight Resident versus 24-hour Attending Radiologist Coverage in Academic
      Medical Centers.
AB  - Academic medical centers have long relied on radiology residents to provide after
      hours coverage, which means that they essentially function with autonomy. In this
      approach, attending radiologist review of resident interpretations occurs the
      following morning, often by subspecialist faculty. In recent years, however, this
      traditional coverage model in academic radiology departments has been challenged
      by an alternative model, the 24-hour attending radiologist coverage. Proponents
      of this new model seek to improve patient care after hours by increasing report
      accuracy and the speed with which the report is finalized. In this article, we
      review the traditional and the 24-hour attending radiologist coverage models. We
      summarize previous studies that indicate that resident overnight error rates are
      sufficiently low so that changing to an overnight attending model may not
      necessarily provide a meaningful increase in report accuracy. Whereas some
      centers completely replaced overnight residents, we note that most centers use a
      hybrid model, and overnight residents work alongside supervising attending
      radiologists, much as they do during the day. Even in this hybrid model,
      universal double reading and subspecialist final review, typical features of the
      traditional autonomous resident coverage model, are generally sacrificed. Because
      of this, changing from resident coverage to coverage by an attending radiologist
      that is 24 hours/day, 7 days/week may actually have detrimental effects to
      patient safety and quality of care provided. Changing to an overnight attending
      radiologist model may also have negative effects on the quality of radiology
      resident training, and it significantly increases cost.

PMID- 30277850
TI  - Changes in nutrient intake and inflammation following an anti-inflammatory diet
      in spinal cord injury.
AB  - OBJECTIVE: The objective of the current study was to describe the observed
      changes in nutrient intakes following a 3-month anti-inflammatory diet, and to
      explore potential relationships between the change in nutrients and the change in
      various inflammatory mediators. DESIGN: A secondary analysis of a prior
      randomized controlled clinical trial. SETTING: Individuals with SCI within the
      Niagara region. PARTICIPANTS: Twenty individuals with various levels and
      severities of SCI. INTERVENTION: Three-month anti-inflammatory diet. OUTCOME
      MEASURES: The change in nutrient intake and corresponding changes to various
      inflammatory mediators. RESULTS: The treatment group demonstrated a significant
      reduction in fat intake (P = 0.02), a significant increase in protein intake (P =
      0.02), and no change in carbohydrates (P = 0.23) or energy intake (P = 0.10). The
      treatment group showed a significant increase in some nutrients with established
      anti-inflammatory properties including vitamins A, C, and E, and omega-3 fatty
      acids (P < 0.01). Significant reductions in proinflammatory nutrients were
      observed including trans fatty acids (P = 0.05), caffeine (P < 0.01), and sodium
      (P = 0.02). The treatment group also showed significant reductions in the
      proinflammatory mediators interferon-y (P = 0.01), interleukin-1beta (P < 0.01),
      and interleukin-6 (P < 0.05). Further, several proinflammatory mediators were
      negatively correlated with anti-inflammatory nutrients, including vitamin A,
      carotenoids, omega-3 fatty acids, and zinc. CONCLUSION: This study provides
      evidence that dietary alterations are effective at reducing chronic inflammation
      in individuals with SCI and provides a preliminary assessment of the related
      nutrient changes.

PMID- 30277851
TI  - Multipoint Bending and Shape Retention of a Pneumatic Bending Actuator by a
      Variable Stiffness Endoskeleton.
AB  - We propose a pneumatic bending actuator integrated with a low-melting-point alloy
      based variable stiffness endoskeleton that can bend at multiple points and
      maintain its bent shape without power supply. Local stiffness of the soft
      actuator can be altered by melting or hardening the endoskeleton with electric
      heat applied through embedded metal wires. Bending points of the actuator can be
      changed by selecting different points of the endoskeleton to be melted, and the
      bending angle can be controlled by injected air pressure. The shape of the bent
      actuator is maintained by hardening the alloy even when pressure is reduced to
      the initial state. We demonstrate that the actuator can be bent differently with
      only one pneumatic actuation layer by combining multipoint bending and the shape
      retention function, and thus the actuator can be used for lifting, holding, and
      unloading an object. We believe that the simple machinery of the actuator will be
      useful in programming complicated motions of soft robotic fingers, fins, and
      tentacles.

PMID- 30277852
TI  - Change in urodynamic pattern and incidence of urinary tract infection in patients
      with traumatic spinal cord injury practicing clean self-intermittent
      catheterization.
AB  - OBJECTIVE: To observe changes in cystometric parameters in individuals with
      spinal cord injury (SCI) with neurogenic bladder practicing clean intermittent
      self-catheterization (CIC) and incidence of urinary tract infection (UTI) in such
      patients. DESIGN: Prospective, observational study. SETTING: Tertiary Urban
      Rehabilitation Hospital. PARTICIPANTS: Persons with neurogenic bladder caused by
      traumatic SCI and practicing CIC. INTERVENTIONS: Clinical evaluation, complete
      urine analysis, urine culture and sensitivity, ultrasonography of the abdomen and
      urodynamic study were evaluated at baseline and at follow-up (6 months to 1
      year). OUTCOME MEASURES: Detrusor pattern, cystometric capacity, detrusor
      compliance, detrusor leak point pressure, residual urine, incidence of UTI.
      RESULTS: Thirty-one participants were included in the study. The baseline
      cystometric study showed that 15 had overactive detrusor and 16 had detrusor
      areflexia. The mean cystometric capacity decreased significantly between baseline
      and follow-up in both the groups but remained within the normal threshold limit,
      decline being more marked in the overactive detrusor group, who also had more
      marked decrease in compliance. Mean detrusor leak point pressure was below 40 cm
      H2O in all participants in both groups at baseline and follow-up. Mean residual
      urine improved at follow-up in both groups. Incidence of UTI was 2.29 episodes
      per patient per year, and more frequent in the overactive detrusor group.
      Escherichia coli was the causative agent in 45%. CONCLUSION: The cystometric
      capacity and compliance decreased significantly though patients were doing
      regular CIC and managed on antimuscarinics for detrusor overactivity (DO). UTI is
      more common in individuals with SCI with DO and E. coli is the most common cause
      of UTI.

PMID- 30277853
TI  - A Chromosome 6, not Natural Killer Cell, Contribution to Radiation- and Bleomycin
      Induced Lung Disease in Mice.
AB  - Inbred strains of mice differ in susceptibility to both radiation-induced and
      bleomycin-induced pulmonary fibrosis and these traits have been mapped to a
      common locus on chromosome 6 which harbors genes of natural killer cell function.
      To investigate this putative locus of fibrosis susceptibility we assessed the
      fibrotic response of chromosome-6 consomic mice (B6.6A), and of mice deficient
      for natural killer cells, C57BL/6J Ly49A transgenic mice, after each of thoracic
      irradiation and bleomycin treatment via osmotic minipump. Thoracic irradiation
      resulted in less than 15% survival at 26 weeks in parental strain C57BL/6J and
      A/J mice, due to the development of pneumonitis with fibrosis in C57BL/6J (B6)
      mice, and pneumonitis in A/J mice. One hundred percent of consomic B6.6A mice
      survived at 26 weeks after thoracic irradiation, and developed a fibrosis level
      similar to that of fibrosis-resistant A/J mice, after irradiation ( P = 0.38) or
      bleomycin challenge ( P = 0.32). C57BL/6J Ly49A transgenic mice were confirmed
      through flow cytometric analysis to be deficient in NK cells, but the post
      irradiation survival of these mice was not significantly different from that of
      wild-type littermate mice ( P = 0.64). Extent of pulmonary fibrosis by
      histological examination did not differ between C57BL/6J Ly49A transgenic mice
      and wild-type littermate mice in response to either irradiation ( P = 0.14) or
      bleomycin treatment ( P = 0.62). We conclude that chromosome 6 genes, but not NK
      cells, contribute to the susceptibility to both radiation-induced and bleomycin
      induced pulmonary fibrosis of C57BL/6J mice.

PMID- 30277854
TI  - The acute effect of training fire exercises on fire service instructors.
AB  - Fire service instructors (FSI) regularly experience different types of fire
      exercises, however the strain experienced from these scenarios is not well
      understood. This study aims to identify the physiological and perceptual strain
      of Fire Service Instructors (FSI) to three training exercises: DEMO, ATTACK,
      COMPARTMENT, and the different roles performed: SETTER, INSTRUCTOR. The study
      also aims to assess the effect that different exercise patterns over a day (BOX,
      MULTI, COMBINATION) have on immunological responses. Sixteen FSI (age: 41 +/- 8
      years, body mass: 83.7 +/- 6.7 kg, height: 177.0+/-6.7 cm) were recruited, with
      10 FSI completing the three exercises. Physiological and perceptual measures were
      collected prior to and immediately post each exercise. Venous blood samples were
      collected at the beginning and end of each day. One way analysis of variance
      (ANOVA) were conducted to assess differences in physiological variables between
      exercise types, independent samples t-tests were conducted between roles. Day
      changes in hematological variables were assessed by paired sample t-tests and
      analyzed by one way ANOVAs to identify differences between exercise patterns. The
      COMPARTMENT exercise resulted in a greater change in rectal temperature
      (DeltaTre) (0.49 +/- 0.28 degrees C) than both the DEMO (0.23 +/- 0.19 degrees C,
      p = 0.045) and ATTACK (0.27 +/- 0.22 degrees C, p = 0.016). Within the
      COMPARTMENT exercise, the SETTER resulted in a greater DeltaTre and rating of
      perceived exertion than the INSTRUCTOR (0.67 +/- 0.29 degrees C vs. 0.43 +/- 0.18
      degrees C, p = 0.027 and 14 +/- 2 vs. 11 +/- 2, p = 0.001, respectively).
      Following a day of fire exercises white blood cells (WBC), neutrophils,
      lymphocytes (LYMPH), monocytes (MONO), platelets (PLT), mean platelet volume
      (MPV), Interleukin (IL)-6, and cardiac troponin T (cTnT) all increased (p <
      0.05). Exercise patterns containing a COMPARTMENT exercise resulted in greater
      PLT, MPV, and IL-6. Total daily variation in DeltaTre was correlated with post
      exercise WBC, MONO, and LYMPH. COMPARTMENT exercises produce the greatest
      physiological strain, with the SETTER role within this exercise causing the
      greatest DeltaTre. Although predominately physiological responses remain within
      safe limits. Exercise patterns that include a COMPARTMENT exercise also generate
      a greater inflammatory response.

PMID- 30277855
TI  - Regulation of C2C12 Differentiation and Control of the Beating Dynamics of
      Contractile Cells for a Muscle-Driven Biosyncretic Crawler by Electrical
      Stimulation.
AB  - Biosyncretic robots have potential advantages associated with both living
      organisms and electromechanical systems. Skeletal muscle tissue is a candidate as
      bioactuators for biosyncretic robots because of its excellent contraction force
      and controllability. However, the low quality of myoblast (C2C12) differentiation
      into contractile myotubes and the lack of control research on biosyncretic robots
      are two of the main challenges in the development of biosyncretic robots. In this
      study, an approach with circularly distributed multiple electrodes (CEs) is
      proposed to improve C2C12 differentiation and to control the movement of a
      myotube-based biosyncretic crawling robot. To analyze the advantages of the
      proposed CEs, the electrical characteristics of CEs and a pair of traditional
      parallel stimulation electrodes (PEs) were simulated and compared with each
      other. Then, to determine the optimal electrical stimulation parameters and
      demonstrate the superiorities of the proposed CEs, electrical pulses with
      different parameters were used to stimulate two-dimensional and three-dimensional
      cells during culture with the proposed CEs and PEs. After this the control
      characteristics of the muscle tissue by the CEs were investigated from the
      relevance of pulse width-threshold voltage, voltage-contractility, frequency
      contractility, and electric field direction-contractility by measuring the real
      time responses of myotubes to different electrical stimulations. Moreover, to
      demonstrate the control of biosyncretic robots by the CEs, a biomimetic
      biosyncretic crawler actuated by myotubes was designed, fabricated, and
      controlled to move at different speeds by varying directions of electric field.
      This study not only provides a potential tool for the development and control of
      biosyncretic robots but is also informative for muscle tissue engineering and
      cardiomyocyte culture.

PMID- 30277856
TI  - Structure and N-acetylglucosamine binding of the distal domain of mouse
      adenovirus 2 fibre.
AB  - Murine adenovirus 2 (MAdV-2) infects cells of the mouse gastrointestinal tract.
      Like human adenoviruses, it is a member of the genus Mastadenovirus, family
      Adenoviridae. The MAdV-2 genome has a single fibre gene that expresses a 787
      residue-long protein. Through analogy to other adenovirus fibre proteins, it is
      expected that the carboxy-terminal virus-distal head domain of the fibre is
      responsible for binding to the host cell, although the natural receptor is
      unknown. The putative head domain has little sequence identity to adenovirus
      fibres of known structure. In this report, we present high-resolution crystal
      structures of the carboxy-terminal part of the MAdV-2 fibre. The structures
      reveal a domain with the typical adenovirus fibre head topology and a domain
      containing two triple beta-spiral repeats of the shaft domain. Through glycan
      microarray profiling, saturation transfer difference nuclear magnetic resonance
      spectroscopy, isothermal titration calorimetry and site-directed mutagenesis, we
      show that the fibre specifically binds to the monosaccharide N-acetylglucosamine
      (GlcNAc). The crystal structure of the complex reveals that GlcNAc binds between
      the AB and CD loops at the top of each of the three monomers of the MAdV-2 fibre
      head. However, infection competition assays show that soluble GlcNAc
      monosaccharide and natural GlcNAc-containing polymers do not inhibit infection by
      MAdV-2. Furthermore, site-directed mutation of the GlcNAc-binding residues does
      not prevent the inhibition of infection by soluble fibre protein. On the other
      hand, we show that the MAdV-2 fibre protein binds GlcNAc-containing mucin
      glycans, which suggests that the MAdV-2 fibre protein may play a role in viral
      mucin penetration in the mouse gut.

PMID- 30277858
TI  - Taurine dioxygenase (tauD)-independent taurine assimilation in Escherichia coli.
AB  - On the basis of previous studies on taurine assimilation in Escherichia coli,
      TauD, an iron- and alpha-ketoglutarate-dependent taurine dioxygenase, has been
      regarded as an indispensable factor for assimilation. However, we found that tauD
      deficient strains did not lose their taurine assimilation ability when there was
      no deletion of ssuD, which encodes a reduced flavin mononucleotide [FMNH(2)]
      dependent alkanesulfonate monooxygenase, which is responsible for the
      desulfonation of alkanesulfonates. There were no significant differences in lag
      phase time, growth rate and final growth yield between the tauD-deficient strain
      and the tauD wild-type strain. Iron increased the growth rate and final growth
      yield of the ssuD mutant, but not those of the tauD mutant. The double deletion
      of tauD and ssuD resulted in the loss of the ability to assimilate taurine. When
      ssuD was artificially expressed in the double-deletion mutant, the mutant
      recovered its taurine assimilation ability. These findings indicate that there is
      another taurine assimilation pathway that is dependent on ssuD but independent of
      tauD.

PMID- 30277857
TI  - Comparative transcriptome analyses of magainin I-susceptible and -resistant
      Escherichia coli strains.
AB  - Antimicrobial peptides (AMPs) have attracted considerable attention because of
      their multiple and complex mechanisms of action toward resistant bacteria.
      However, reports have increasingly highlighted how bacteria can escape AMP
      administration. Here, the molecular mechanisms involved in Escherichia coli
      resistance to magainin I were investigated through comparative transcriptomics.
      Sub-inhibitory concentrations of magainin I were used to generate four
      experimental groups, including magainin I-susceptible E. coli, in the absence (C)
      and presence of magainin I (CM); and magainin I-resistant E. coli in the absence
      (R) and presence of magainin I (RM). The total RNA from each sample was
      extracted; cDNA libraries were constructed and further submitted for Illumina
      MiSeq sequencing. After RNA-seq data pre-processing and functional annotation, a
      total of 103 differentially expressed genes (DEGs) were identified, mainly
      related to bacterial metabolism. Moreover, down-regulation of cell motility and
      chaperone-related genes was observed in CM and RM, whereas cell communication,
      acid tolerance and multidrug efflux pump genes (ABC transporter, major
      facilitator and resistance-nodulation cell division superfamilies) were up
      regulated in these same groups. DEGs from the C and R groups are related to basal
      levels of expression of homeostasis-related genes compared to CM and RM,
      suggesting that the presence of magainin I is required to change the
      transcriptomics panel in both C and R E. coli strains. These findings show the
      complexity of E. coli resistance to magainin I through the rearrangement of
      several metabolic pathways involved in bacterial physiology and drug response,
      also providing information on the development of novel antimicrobial strategies
      targeting resistance-related transcripts and proteins herein described.

PMID- 30277859
TI  - The challenge of pet therapy in systemic sclerosis: evidence for an impact on
      pain, anxiety, neuroticism and social interaction.
AB  - OBJECTIVES: The aim of our study was to evaluate the effect of animal-assisted
      intervention (AAI), a complementary support to traditional therapies focused on
      the interaction between animals and human beings, in improving psychological
      trait, anxiety and pain in a cohort of systemic sclerosis (SSc) patients.
      METHODS: 42 SSc patients, undergoing iloprost intravenous infusion, were divided
      in three groups: 1) 14 patients submitted to 20 AAI sessions; 2) 14 patients
      engaged in alternative social activity (control group 1 - C1); and 3) 14 patients
      without any alternative activity (control group 2 - C2). All patients underwent
      Visual Analog Scale (VAS), the State-anxiety (STAI-S) and emotional faces at the
      beginning (s0) and at the end (s1) of each single session, while General Anxiety
      State-Trait Anxiety Inventory (STAI-T), Beck Depression Inventory (BDI), Social
      Interaction Anxiety Scale (SIAS), Eysenck Personality Questionnaire-Revised (EPQ
      R), the Social Phobia Scale (SPS), the Toronto Alexythymia Scale (TAS-20), the
      Thought Control Questionnaire (TCQ) were administered at baseline (t0) and at the
      end of the project (t1). RESULTS: AAI group showed a significant decrease of the
      anxiety state level in respect to the two control groups (p<0.001). VAS scale
      resulted lower both in AAI (p < 0.001) and C1 group (p<0.01). Moreover, STAI-T
      and TAS scores were significantly reduced in AAI group (p<0.001). TCQ scale
      showed that patients treated with AAI, compared to control group C2, had greater
      capacity to avoid unpleasant and unwanted thoughts (p<0.05). In AAI group, the
      EPQ-R test revealed an enhancement of extroversion trait compared to both control
      groups (p<0.05). CONCLUSIONS: Our data show that AAI significantly reduces pain
      perception, anxiety, neuroticism and ameliorates patients' social interaction,
      therefore it may be a useful to allow a better compliance to traditional
      therapies.

PMID- 30277861
TI  - Simultaneous inhibition of c-Abl and Src kinases abrogates the exaggerated
      expression of profibrotic genes in cultured systemic sclerosis dermal
      fibroblasts.
AB  - OBJECTIVES: To examine the effects of simultaneous inhibition of c-Abl and Src
      kinases on the gene expression and in vitro production of profibrotic molecules
      by dermal fibroblasts from patients with diffuse systemic sclerosis (SSc) of
      recent onset. METHODS: Dermal fibroblasts from normal individuals or from
      patients with diffuse cutaneous SSc fulfilling the American College of
      Rheumatology/EULAR SSc classification criteria were cultured in media containing
      increasing concentrations of the dual c-Abl and Src kinase inhibitor Bosutinib
      for 24 h. Total soluble collagen in cell culture supernatants was quantified.
      Western blots were performed for quantitative assessment of type I collagen,
      fibronectin, and alpha-smooth muscle actin (alpha-SMA) production. Quantitative
      PCR was performed to examine the effects of Bosutinib on the expression of
      profibrotic and TGF-beta-responsive genes in cultured SSc dermal fibroblasts.
      RESULTS: Simultaneous inhibition of c-Abl and Src kinases with Bosutinib reduced
      the expression of numerous fibrosis-associated genes including COL1A1, COL1A3,
      FN, and TGFbeta and the production of the corresponding proteins by SSc dermal
      fibroblasts. Bosutinib also decreased the transition of normal dermal fibroblasts
      into activated myofibroblasts induced by TGF-beta as evidenced by reduction of
      alpha-SMA in cell extracts from normal and SSc dermal fibroblasts. CONCLUSIONS:
      Simultaneous inhibition of c-Abl and Src kinases with Bosutinib abrogates the
      exaggerated expression of genes encoding fibrillar collagens, fibronectin, and
      TGF-beta-responsive genes and reduces type I collagen, fibronectin and alpha-SMA
      production by SSc dermal fibroblasts in vitro. Bosutinib also abrogates TGF- beta
      induced transition of normal fibroblasts to activated myofibroblasts. These
      results indicate that inhibition of c-Abl and Src kinases activity may be an
      effective disease modifying antifibrotic therapeutic intervention for SSc.

PMID- 30277860
TI  - Gender differences in early systemic sclerosis patients: a report from the EULAR
      scleroderma trials and research group (EUSTAR) database.
AB  - OBJECTIVES: To describe differences in clinical presentation between men and
      women in a large group of patients with early (<3 years' duration) systemic
      sclerosis (SSc) according to disease subsets. METHODS: A cross-sectional analysis
      of the prospective EULAR Scleroderma Trial and Research database (EUSTAR) was
      performed. Patients fulfilling preliminary ACR 1980 classification criteria for
      SSc, with less than 3 years from the first non-Raynaud's symptom at first entry,
      were selected. A group of patients with less than 3 years from the first SSc
      symptom, including Raynaud's phenomenon, was also analysed. SSc related
      variables, including antibodies, SSc subsets, disease activity and organ
      involvement were included. Descriptive and bivariate analyses were performed.
      RESULTS: A total of 1,027 patients were included, 90% Caucasian, 80% women, and
      40% with diffuse cutaneous disease. In early stages of SSc, men showed more
      frequently than women active disease, diffuse cutaneous subset, anti-Scl-70
      antibodies, elevated acute phase reactants, muscular and pulmonary involvement.
      Differences between men and women were confirmed in the limited, but not in the
      diffuse SSc subset. The results were similar when 650 patients with less than
      three years from the first SSc symptom, including Raynaud's phenomenon, were
      analysed. CONCLUSIONS: In early stages of SSc, men present signs and symptoms of
      more severe disease. In the limited disease subset, men might appear with
      clinical features and organ involvement similar to those of the diffuse subgroup.
      In clinical practice, the identification of such differences might help to select
      the appropriate management for each particular patient.

PMID- 30277862
TI  - Randomised, double-blind, placebo-controlled trial of IL1-trap, rilonacept, in
      systemic sclerosis. A phase I/II biomarker trial.
AB  - OBJECTIVES: This clinical trial was designed to study the safety and efficacy of
      blocking IL-1 in skin fibrosis of patients with diffuse cutaneous systemic
      sclerosis (dcSSc), and to test the hypothesis that inhibition of IL-1 by
      rilonacept will downregulate expression of the 2G SSc gene biomarker as a
      surrogate for the modified Rodnan skin score (MRSS). METHODS: 19 dcSSc patients
      were randomised 2:1 active treatment:placebo in this double blinded trial. Study
      patients received weekly treatments with either subcutaneous rilanocept 320 mg
      loading dose at day 0 and then 160 mg for each of the 5 subsequent weekly doses,
      or placebo. Skin biopsies were taken to test 2G SSc biomarker gene expression at
      day 0 before treatment and one week after the final study drug dose, comparing
      gene expression changes between rilonacept- and placebo-treated patients, as well
      as the change in gene expression at week 6 compared to baseline in rilonacept
      treated patients. Safety assessments extended to 6 weeks after the final dose of
      study drug or placebo. Other secondary outcome measures included global and IL-1
      regulated gene expression, serum biomarkers and the MRSS. RESULTS: Rilonacept
      compared to placebo-treated patients did not show any treatment-related effect on
      the 2G SSc biomarker. Rilonacept treatment also failed to alter IL-6 expression
      in skin, serum IL-6, C-reactive protein, or CCL18, a marker of IL-6 activity in
      SSc. CONCLUSIONS: In this small trial we did not observe any effect of blocking
      IL-1 on clinical skin disease or biomarkers of IL-1 activity.

PMID- 30277863
TI  - Usefulness of six-minute walk test in systemic sclerosis.
AB  - The 6-minute walk test (6MWT) is a standardised, feasible and reliable measure of
      sub-maximal exercise capacity that has never been fully validated in systemic
      sclerosis (SSc). A variety of data suggest that many non-pulmonary aspects of SSc
      contribute to the test results, thus blunting the ability of the 6MWT to measure
      changes in lung function. Sources of variability are a training effect,
      technician experience, subject encouragement, medication, other activities on day
      of testing, deconditioning and the effects of musculoskeletal conditions and
      pain. Another cause of variability is the anatomical site the probe is attached
      to: a forehead probe is preferable to a finger or earlobe sensor. The
      indiscriminate use of the 6MWT for all SSc patients is not useful. It should be
      used in patients with pulmonary involvement, combined with diffusion capacity of
      the lung for carbon monoxide (DLCO) and its components (membrane diffusion and
      capillary volume) or the Sclerodermia Health Assessment Questionnaire Disability
      Index. The use of these combined parameters may indicate the onset of pulmonary
      hypertension. Recent studies suggest two alternatives to the 6MWT: maximal
      cardiopulmonary exercise testing and DLCO testing during effort. However, their
      use must still be validated.

PMID- 30277864
TI  - Combination therapy with rituximab and mycophenolate mofetil in systemic
      sclerosis. A single-centre case series study.
AB  - OBJECTIVES: To describe a single centre experience using combination therapy with
      rituximab (RTX) and mycophenolate mofetil (MMF) in a prospective series of
      systemic sclerosis (SSc) patients with pulmonary and cutaneous involvement,
      rapidly progressive or resistant to conventional therapy. METHODS: RTX was
      administered in two different regimens (1000 mg fortnightly x 2 or 375 mg/m2/week
      for 4 consecutive weeks) at baseline and after 6 months, associated with MMF 2000
      mg/day continuously. Cutaneous fibrosis was evaluated assessing modified Rodnan
      Skin Score (mRSS) and pulmonary involvement was evaluated performing pulmonary
      function tests, diffusing lung capacity for carbon monoxide and chest high
      resolution computed tomography (HRCT). The radiological extension of the
      interstitial lung disease (ILD) at HRCT, was assessed with the conventional
      visual reader-based score (CoVR) and with a computerised-aided method (CaM) using
      a DICOM soft- ware. RESULTS: Eighteen SSc patients underwent combination therapy
      (F/M: 10/8, median age 51 years, median duration of disease 27 months). Data from
      fifteen patients were available at 12-month follow-up. The mRSS showed a
      significant improvement; a significant increase in forced vital capacity and
      forced expiratory volume in the first second were also observed. In addition, a
      signi cant reduction of the extension of ILD was detected when evaluated with
      CaM. No serious adverse events were observed during the follow-up period.
      CONCLUSIONS: Despite preliminary results and limited to a small number of
      patients, our data suggest that therapy with RTX and MMF is well tolerated, safe,
      and potentially effective for cutaneous and pulmonary involvement in SSc.

PMID- 30277865
TI  - The association of sociodemographic and disease variables with hand function: a
      Scleroderma Patient-centered Intervention Network cohort study.
AB  - OBJECTIVES: Impaired hand function in systemic sclerosis (SSc) is a primary cause
      of disability and contributes diminished health-related quality of life. The
      objective of the present study was to evaluate sociodemographic, lifestyle, and
      disease-related factors independently associated with hand function in SSc.
      METHODS: Patients enrolled in the Scleroderma Patient-centered Intervention
      Network Cohort who completed baseline study questionnaires between March 2014 and
      September 2017 were included. Hand function was measured using the Cochin Hand
      Function Scale (CHFS). Multiple linear regression analysis was used to identify
      independent correlates of impaired hand function. RESULTS: Among 1193
      participants (88% female), the mean CHFS score was 13.3 (SD=16.1). Female sex
      (standardised regression coefficient, beta (beta)=.05), current smoking
      (beta=.07), higher BMI (beta=.06), diffuse SSc (beta=0.14), more severe Raynaud's
      scores (beta=.23), more severe finger ulcer scores (beta=.23), moderate
      (beta=0.19) or severe small joint contractures (beta=.20), rheumatoid arthritis
      (beta=0.07), and idiopathic inflammatory myositis (beta=0.06) were significantly
      associated with higher CHFS scores (more impaired hand function). Consumption of
      1-7 alcoholic drinks per week (beta=-0.07) was associated with lower CHFS scores
      (less impaired hand function) compared to no drinking. CONCLUSIONS: Multiple
      factors are associated with hand function in SSc. The presence of moderate or
      severe small joint contractures, the presence of digital ulcers, and severity of
      Raynaud's phenomenon had the largest associations. Effective interventions are
      needed to improve the management of hand function in patients with SSc.

PMID- 30277866
TI  - Dickkopf-1 is downregulated early and universally in the skin of patients with
      systemic sclerosis despite normal circulating levels.
AB  - OBJECTIVES: The activity of the Wnt pathway, a critical mediator of fibrosis, is
      regulated by Dickkopf-1 (Dkk-1). Dkk-1 is absent from scleroderma skin in
      contrast to skin from healthy subjects where it is clearly expressed. There are
      no data on circulating levels and function of Dkk-1 in patients with systemic
      sclerosis (SSc). Our objectives are to assess: i) circulating and functional
      levels of Dkk-1 in patients with SSc and ii) whether the striking lack of Dkk-1
      skin expression is also evident in a) clinically uninvolved skin from patients
      with SSc and b) very early disease prior to skin thickening. METHODS: Circulating
      Dkk-1 levels were measured in 50 patients with SSc and 50 controls. Skin biopsies
      were obtained from SSc patients from a) clinically involved skin b) clinically
      uninvolved skin, c) oedematous skin prior to skin thickening. RESULTS:
      Circulating and functional Dkk-1 levels were similar in patients with SSc and
      controls. Healthy skin displayed a high Dkk-1 immuno-expression in the epidermis
      and dermal fibroblasts in contrast to clinically involved scleroderma skin where
      Dkk-1 was totally absent. In all biopsies of clinically uninvolved skin Dkk-1 was
      only moderately expressed whereas skin from very early disease displayed only a
      weak Dkk-1 immunoreactivity. CONCLUSIONS: The downregulation of Dkk-1 at the
      oedematous phase of the disease indicates that the Wnt pathway is involved early
      in the disease process and may play a role in driving fibrosis. The decrease in
      Dkk-1 expression in clinically uninvolved scleroderma skin indicates that skin in
      SSc is universally affected.

PMID- 30277867
TI  - Implications of endothelial shear stress on systemic sclerosis vasculopathy and
      treatment.
AB  - There are no Federal Drug Administration approved drugs for the treatment of
      systemic sclerosis vascular digital ulcers (DU) in the United States, which are
      thought to be an end-stage result of prolonged ischaemia due to severe, prolonged
      Raynaud's phenomenon. Most therapeutics for vasodilation used in SSc work
      different pathways to target the smooth muscle to induce vessel relaxation.
      Longitudinal studies of vascular function allow insight into the effects of
      medications used for Raynaud's phenomenon in the SSc patient population. In this
      review, we discuss vascular tone, the function of the endothelium in SSc, and
      provide the rationale for longitudinal studies of vascular function and
      therapeutics that target the endothelial shear stress in addition to vasodilation
      for treatment and prevention of DU. This review provides the rationale for
      vasodilatory medication use for treatment of SSc-related DU and justifies access
      to non-FDA approved medications for this indication.

PMID- 30277868
TI  - One year in review 2018: systemic sclerosis.
AB  - Systemic sclerosis is a rare acquired systemic disease characterised by a complex
      pathogenesis and multi organ involvement. Every year the scientific world
      contributes to enrich the knowledge on the pathogenesis, clinical manifestations,
      diagnosis and treatment of this complex and severe disease. Herewith, we provide
      an overview of the most significant literature contributions published over the
      last year.

PMID- 30277870
TI  - A shared future for all: let's talk about homelessness.

PMID- 30277869
TI  - The role of inflammatory markers in assessment of disease activity in systemic
      sclerosis.
AB  - OBJECTIVES: The role of the erythrocyte sedimentation rate (ESR) and C-reactive
      protein (CRP) in the assessment of disease activity in systemic sclerosis (SSc)
      remains controversial. We sought to evaluate the relationship between clinical
      features of SSc and raised inflammatory markers and to determine if changes in
      ESR and CRP reflect changes in other disease features over time. METHODS: One
      thousand, five hundred and forty-five patients enrolled in the Australian
      Scleroderma Cohort Study were observed over a mean 3.52+/-2.91 years and assessed
      at 6,119 study visits. Generalised estimating equations were used to determine
      the relationship between ESR>=20mm/hr and CRP>=5mg/L and features of disease. The
      associations between change in inflammatory markers and change in skin scores and
      respiratory function tests were analysed. RESULTS: Overall, there was a
      significant association between raised ESR and forced vital capacity (FVC)<80%
      predicted, diffusing capacity of the lung (DLCO)<80% predicted, pulmonary
      arterial hypertension (PAH), body mass index (BMI), proximal muscle strength,
      anaemia, and hypocomplementaemia (p<0.05). Raised CRP was significantly
      associated with modified Rodnan Skin Score>20, FVC<80%, DLCO<80%, PAH, digital
      ulcers, BMI, synovitis, tendon friction rub, anaemia, and hypocomplementaemia
      (p<0.05). A significant deterioration in respiratory function tests (RFTs) was
      associated with a 2-fold increase in both ESR and CRP (p<0.05). CONCLUSIONS:
      Raised inflammatory markers are associated with pulmonary, cutaneous and
      musculoskeletal manifestations of SSc. Rising inflammatory markers are correlated
      with declining respiratory function tests. This suggests inflammatory markers
      have a role in the assessment of SSc disease activity.

PMID- 30277871
TI  - The peril and promise of traffic.

PMID- 30277872
TI  - Preparing for seasonal influenza.

PMID- 30277873
TI  - The Lancet-CAMS Health Summit 2018: a call for abstracts.

PMID- 30277875
TI  - Offline: The misuse of universal health coverage.

PMID- 30277874
TI  - A time to remember and thank The Lancet's reviewers of 2017.

PMID- 30277876
TI  - Changes in the US tax system will also affect health care.

PMID- 30277877
TI  - Bolivia backtracks on malpractice law.

PMID- 30277878
TI  - Universal health coverage law approved in Egypt.

PMID- 30277879
TI  - Type 1 diabetes.

PMID- 30277880
TI  - Health care as a cultural borderland.

PMID- 30277881
TI  - A public health approach to opioid addiction in North America.

PMID- 30277882
TI  - A new era for medical education in Colombia.

PMID- 30277883
TI  - The definition of acute kidney injury.

PMID- 30277884
TI  - A public health approach to opioid addiction in North America - Author's reply.

PMID- 30277885
TI  - The definition of acute kidney injury - Authors' reply.

PMID- 30277886
TI  - Single nanowire measurements of room temperature ferromagnetism in FeSi nanowires
      and the effects of Mn-doping.
AB  - Semiconductors with magnetic response at room temperature are sought for
      spintronics in solid-state devices. Among possible materials for this
      applications, the magnetic response of FeSi and doped FeSi have produced
      contradictory results at the nanoscale and more precise measurements and deeper
      studies are needed to clarify its potential capabilities. For that reason, in
      this work, single nanowire measurements of ferromagnetic semiconducting FeSi and
      Mn-doped FeSi nanostructures have been performed using magnetic force microscopy
      and electron holography. Results obtained confirm the presence of magnetic
      domains at room temperature with a magnetic moment per Fe atom of [Formula: see
      text] Spin polarized density functional calculations confirm a net magnetic
      moment between [Formula: see text] in Fe surface atoms with an estimated Curie
      temperature of 417 K by means of the molecular field approximation. The nanowires
      present a crystalline B20 cubic structure as confirmed by x-ray diffraction and
      high-resolution electron microscopy. Their electrical transport measurements
      confirm p-type nature and thermal activation. A remanent magnetization of 1.5 *
      10-5 emu and 0.5 * 10-5 emu was measured at room temperature for FeSi and Mn
      doped FeSi respectively, with spin freezing behavior around 30 K for the Mn-doped
      nanowires.

PMID- 30277887
TI  - Effects of acrylate/acrylamide polymers on the adhesion, growth and
      differentiation of Muse cells.
AB  - BACKGROUND: Acrylate/acrylamide copolymers have excellent optical properties and
      biocompatibility and are ideal biomaterials that have been widely used in tissue
      engineering. Multilineage-differentiating stress-enduring cells (Muse cells) are
      a specific subset of mesenchymal stem cells that have an excellent potential for
      the regenerative medicine. OBJECTIVE: This study was designed to investigate the
      effects of acrylate/acrylamide copolymers on the adhesion, proliferation and
      pluripotent-like properties of Muse cells, which were derived from normal human
      dermal fibroblasts by long-term trypsin incubation. METHODS: In an initial
      experiment, Muse cells were seeded on primary microarrays containing micro-spots
      of 275 different mixtures of acrylate/acrylamide. Each mixture was composed of
      two of 11 different monomers in various proportions, and was replicated in four
      micro-spots each. According to the adhesion and growth characteristics of Muse
      cells on those substrates, specific polymer candidates for Muse cells were
      selected and secondary microarrays were prepared. We then observed the effects of
      those specific polymer candidates on the adherence, proliferation and
      differentiation of Muse cells and suitable candidates for their optimal culture
      were identified. RESULTS: According to the adhesion and growth patterns of Muse
      cells on the primary microarrays, ten suitable mixtures of acrylate/acrylamide
      copolymers were identified. Muse cells grew well on six of those combinations and
      around the four other combinations of those polymer mixtures. Muse cells cultured
      on three of those combinations proliferated and differentiated into long spindle
      shaped cells that looked like fibroblasts, while Muse cells cultured on one
      combination formed clusters that were ring-shaped. Muse cells cultured on some of
      those combinations of acrylate/acrylamide proliferated and formed clusters that
      appeared to be very healthy, whereas Muse cells cultured on other combinations
      formed clusters that expanded outwards. CONCLUSIONS: These results identified a
      polymer combination that was optimum for the adhesion, proliferation and
      maintenance of Muse cells in an undifferentiated state.

PMID- 30277888
TI  - Short-term post-implantation dynamics of in vitro engineered human
      microvascularized adipose tissues.
AB  - Engineered adipose tissues are developed for their use as substitutes for tissue
      replacement in reconstructive surgery. To ensure a timely perfusion of the
      grafted substitutes, different strategies can be used such as the incorporation
      of an endothelial component. In this study, we engineered human adipose tissue
      substitutes comprising of functional adipocytes as well as a natural
      extracellular matrix using the self-assembly approach, without the use of
      exogenous scaffolding elements. Human microvascular endothelial cells (hMVECs)
      were incorporated during tissue production in vitro and we hypothesized that
      their presence would favor the early connection with the host vascular network
      translating into functional enhancement after implantation into nude mice in
      comparison to the substitutes that were not enriched in hMVECs. In vitro, no
      significant differences were observed between the substitutes in terms of
      histological aspects. After implantation, both groups presented numerous
      adipocytes and an abundant matrix in addition to the presence of host capillaries
      within the grafts. The substitutes thickness and volume were not significantly
      different between groups over the short-term time course of 14 days (d). For the
      microvascularized adipose tissues, human CD31 staining revealed a human capillary
      network connecting with the host microvasculature as early as 3 d after grafting.
      The detection of murine red blood cells within human CD31+ structures confirmed
      the functionality of the human capillary network. By analyzing the extent of the
      global vascularization achieved, a tendency towards increased total capillary
      network surface and volume was revealed for prevascularized tissues over 14 d.
      Therefore, applying this strategy on thicker reconstructed adipose tissues with
      rate-limiting oxygen diffusion might procure added benefits and prove useful to
      provide voluminous substitutes for patients suffering from adipose tissue loss or
      defects.

PMID- 30277889
TI  - Reliable gene mutation prediction in clear cell renal cell carcinoma through
      multi-classifier multi-objective radiogenomics model.
AB  - Genetic studies have identified associations between gene mutations and clear
      cell renal cell carcinoma (ccRCC). Since the complete gene mutational landscape
      cannot be characterized through biopsy and sequencing assays for each patient,
      non-invasive tools are needed to determine the mutation status for tumors.
      Radiogenomics may be an attractive alternative tool to identify disease genomics
      by analyzing amounts of features extracted from medical images. Most current
      radiogenomics predictive models are built based on a single classifier and
      trained through a single objective. However, since many classifiers are
      available, selecting an optimal model is challenging. On the other hand, a single
      objective may not be a good measure to guide model training. We proposed a new
      multi-classifier multi-objective (MCMO) radiogenomics predictive model. To obtain
      more reliable prediction results, similarity-based sensitivity and specificity
      were defined and considered as the two objective functions simultaneously during
      training. To take advantage of different classifiers, the evidential reasoning
      (ER) approach was used for fusing the output of each classifier. Additionally, a
      new similarity-based multi-objective optimization algorithm (SMO) was developed
      for training the MCMO to predict ccRCC related gene mutations (VHL, PBRM1 and
      BAP1) using quantitative CT features. Using the proposed MCMO model, we achieved
      a predictive area under the receiver operating characteristic curve (AUC) over
      0.85 for VHL, PBRM1 and BAP1 genes with balanced sensitivity and specificity.
      Furthermore, MCMO outperformed all the individual classifiers, and yielded more
      reliable results than other optimization algorithms and commonly used fusion
      strategies.

PMID- 30277891
TI  - County-Level Socioeconomic Disparities in Use of Medical Services for Management
      of Infections by Medicare Beneficiaries With Diabetes-United States, 2012.
AB  - OBJECTIVE: To assess county-level socioeconomic disparities in medical service
      usage for infections among Medicare beneficiaries with diabetes (MBWDs) who had
      fee-for-service health insurance claims during 2012. DESIGN: We used Medicare
      claims data to calculate percentage of MBWDs with infections. SETTING: Medicare
      beneficiaries. PARTICIPANTS: We estimated the percentage of MBWDs who used
      medical services for each of 3 groups of infections by sex and quintiles of the
      prevalence of social factors in the person's county of residence: anatomic site
      specific infections; pathogen-specific infections; and HHST infections (human
      immunodeficiency virus/acquired immunodeficiency syndrome, viral hepatitis,
      sexually transmitted diseases, and tuberculosis). MAIN OUTCOME MEASURES: Using
      quintiles of county-specific socioeconomic determinants, we calculated absolute
      and relative disparities in each group of infections for male and female MBWDs.
      We also used regression-based summary measures to estimate the overall average
      absolute and relative disparities for each infection group. RESULTS: Of the 4.5
      million male MBWDs, 15.8%, 25.3%, and 2.7% had 1 or more site-specific, pathogen
      specific, and HHST infections, respectively. Results were similar for females (n
      = 5.2 million). The percentage of MBWDs with 1 or more infections in each group
      increased as social disadvantage in the MBWDs' county of residence increased.
      Absolute and relative county-level socioeconomic disparities in receipt of
      medical services for 1 or more infections (site- or pathogen-specific) were 12.9
      or less percentage points and 65.5% or less, respectively. For HHST infections,
      percentage of MBWDs having 1 or more HHST infections for persons residing in the
      highest quintile (Q5) was 3- to 4-fold higher (P < .001) than persons residing in
      the lowest quintile (Q1). CONCLUSIONS: Infection burden among MBWDs is generally
      associated with county-level contextual socioeconomic disadvantage, and the
      extent of health disparities varies by infection category, socioeconomic factor,
      and quintiles of socioeconomic disadvantage. The findings imply ongoing need for
      efforts to identify effective interventions for reducing county-level social
      disparities in infections among patients with diabetes.

PMID- 30277892
TI  - Effect of Body Weight-Supported Exercise on Symptoms of Knee Osteoarthritis: A
      Follow-up Investigation.
AB  - OBJECTIVE: To examine the long-term effect of participation in a 12-week lower
      body positive pressure (LBPP)-supported low-load treadmill exercise regime on
      knee joint pain, physical function, and thigh muscle strength in patients with
      knee osteoarthritis (OA). DESIGN: Prospective, observational, repeated measures.
      SETTING: Clinical orthopedic setting. PATIENTS: Nineteen overweight patients with
      knee OA. INTERVENTION: Participants exercised under low-load treadmill walking
      conditions 2*/week for 12 weeks using an amount of LBPP support that minimized
      knee pain while walking for a period of 30 minutes at a set speed of 3.1 mph at 0
      degree incline. MAIN OUTCOME MEASURES: Knee pain, function, thigh muscle
      strength, and body anthropometry were reassessed a minimum of 6 months after
      completion of the initial exercise regime and compared with results from baseline
      and postexercise evaluation. RESULTS: Data suggested that: (1) patients were able
      to maintain improvements in knee joint pain and symptoms; (2) patients continued
      to report enhanced joint function and improved quality of life; and (3) patients
      maintained thigh muscle strength gains. Finally, a majority of patients continued
      to experience significant reductions in acute knee pain during full weight
      bearing treadmill walking. CONCLUSIONS: Data suggest that improvements in knee
      pain, joint function, and thigh muscle strength associated with participation in
      a 12-week LBPP-supported low-load exercise regime were maintained well after
      cessation of the program. These findings have important implications for the
      development and refinement of exercise strategies and interventions used in the
      long-term management of joint symptoms associated with knee OA in overweight
      patients.

PMID- 30277890
TI  - Randomized Feasibility Trial of a Low Tidal Volume-Airway Pressure Release
      Ventilation Protocol Compared With Traditional Airway Pressure Release
      Ventilation and Volume Control Ventilation Protocols.
AB  - OBJECTIVES: Low tidal volume (= tidal volume <= 6 mL/kg, predicted body weight)
      ventilation using volume control benefits patients with acute respiratory
      distress syndrome. Airway pressure release ventilation is an alternative to low
      tidal volume-volume control ventilation, but the release breaths generated are
      variable and can exceed tidal volume breaths of low tidal volume-volume control.
      We evaluate the application of a low tidal volume-compatible airway pressure
      release ventilation protocol that manages release volumes on both clinical and
      feasibility endpoints. DESIGN: We designed a prospective randomized trial in
      patients with acute hypoxemic respiratory failure. We randomized patients to low
      tidal volume-volume control, low tidal volume-airway pressure release
      ventilation, and traditional airway pressure release ventilation with a planned
      enrollment of 246 patients. The study was stopped early because of low enrollment
      and inability to consistently achieve tidal volumes less than 6.5 mL/kg in the
      low tidal volume-airway pressure release ventilation arm. Although the primary
      clinical study endpoint was PaO2/FIO2 on study day 3, we highlight the
      feasibility outcomes related to tidal volumes in both arms. SETTING: Four
      Intermountain Healthcare tertiary ICUs. PATIENTS: Adult ICU patients with
      hypoxemic respiratory failure anticipated to require prolonged mechanical
      ventilation. INTERVENTIONS: Low tidal volume-volume control, airway pressure
      release ventilation, and low tidal volume-airway pressure release ventilation.
      MEASUREMENTS AND MAIN RESULTS: We observed wide variability and higher tidal
      (release for airway pressure release ventilation) volumes in both airway pressure
      release ventilation (8.6 mL/kg; 95% CI, 7.8-9.6) and low tidal volume-airway
      pressure release ventilation (8.0; 95% CI, 7.3-8.9) than volume control (6.8; 95%
      CI, 6.2-7.5; p = 0.005) with no difference between airway pressure release
      ventilation and low tidal volume-airway pressure release ventilation (p = 0.58).
      Recognizing the limitations of small sample size, we observed no difference in 52
      patients in day 3 PaO2/ FIO2 (p = 0.92). We also observed no significant
      difference between arms in sedation, vasoactive medications, or occurrence of
      pneumothorax. CONCLUSIONS: Airway pressure release ventilation resulted in
      release volumes often exceeding 12 mL/kg despite a protocol designed to target
      low tidal volume ventilation. Current airway pressure release ventilation
      protocols are unable to achieve consistent and reproducible delivery of low tidal
      volume ventilation goals. A large-scale efficacy trial of low tidal volume-airway
      pressure release ventilation is not feasible at this time in the absence of an
      explicit, generalizable, and reproducible low tidal volume-airway pressure
      release ventilation protocol.

PMID- 30277893
TI  - No Difference in Return to Sport and Other Outcomes Between Operative and
      Nonoperative Treatment of Medial Epicondyle Fractures in Pediatric Upper
      Extremity Athletes.
AB  - OBJECTIVE: Compare outcomes of operative and nonoperatively managed medial
      epicondyle fractures in upper-extremity athletes. DESIGN: Retrospective chart
      review and phone survey. SETTING: Level 1, tertiary-referral pediatric hospital.
      PATIENTS: Propensity scores (probability of operative treatment) were estimated
      from a logistic regression model that included sex, age, displacement, limb
      dominance, and injury severity (presence of an additional fracture, nerve injury,
      or elbow dislocation). These were used to match subjects in the operative group
      to the nonoperative group. MAIN OUTCOME MEASURES: Return to sport, duration of
      time required to return to sport, pain, range of motion (ROM), need for physical
      therapy, and complications were recorded for both groups. RESULTS: Twenty-eight
      nonoperative subjects were matched to 14 operative subjects. There was no
      significant difference in the proportion of subjects who returned to the same
      sport (92.9% in each group), performance at preinjury level of competition, or
      median time to return to play (P = 0.7106). There was no significant difference
      in functional limitations in social-/work-related activities (P > 0.9999), pain
      in the past 30 days (P = 0.0640), need for physical therapy (P = 0.5680), ROM
      limitations (P = 0.0988), difficulty in sleeping (P = 0.4773), or complications
      (P = 0.4081). CONCLUSIONS: Our study found no statistical difference in outcomes
      or complications between operative and nonoperatively treated moderately
      displaced medial epicondyle fractures in adolescent upper-extremity athletes. Our
      data show that similar outcomes may be achieved with both treatment groups for
      medial epicondyle fractures in upper-extremity athletes.

PMID- 30277894
TI  - Talking Tots and the Terrible Twos: Early Language and Disruptive Behavior in
      Toddlers.
AB  - OBJECTIVE: The goal of this article is to investigate the association between the
      2 most commonly reported parental concerns about young children-disruptive
      behavior (e.g., irritable, aggressive, and noncompliant behaviors) and language
      delay in toddlers. To test for salient subgroup differences, individual
      differences by the sex of the child and family poverty status were examined.
      METHODS: Participants included 1259 mothers of children between 18 and 36 months
      of age. Mothers completed questions about their child's language development and
      disruptive behavior. Information regarding poverty status as well as child age
      and sex were also collected. RESULTS: Stronger language skills were associated
      with fewer disruptive behaviors for children between 18 and 36 months of age.
      This negative association was stronger for females than for males (b = -0.243;
      t[1251] = -3.555; p < 0.001) and stronger for children living in poverty than for
      those above the poverty line (b = -2.04; t[1251] = -2.531; p = 0.011).
      CONCLUSION: Findings from our study suggest a developmental co-occurrence pattern
      that begins at a very early age. Individual differences suggest that there is
      substantial heterogeneity in these patterns; longitudinal investigation is needed
      to uncover causal pathways and underlying mechanisms. Awareness of the
      association between these 2 developmental domains, about which parents frequently
      express concerns, is critical to maximizing early detection and intervention.

PMID- 30277897
TI  - Platelet-Rich Plasma Therapy for Male and Female Pattern Hair Loss.

PMID- 30277895
TI  - Performance of the Pediatric Index of Mortality 3 Score in PICUs in Argentina: A
      Prospective, National Multicenter Study.
AB  - OBJECTIVE: To assess the performance of the Pediatric Index of Mortality 3 score
      in a population of children admitted to PICUs in Argentina. DESIGN: Prospective,
      national, multicenter study. SETTING: Forty-nine PICUs located in Argentina
      belonging to public and private institutions. PATIENTS: All children between 1
      month and 16 years old admitted to the participating PICUs between May 15, 2016,
      and February 15, 2017. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: A total
      of 6,602 patients were enrolled in the study. The observed mortality was 8%
      (531/6,602), whereas mortality predicted by Pediatric Index of Mortality 3 was
      6.16% (407 deaths). The standardized mortality rate was 1.3 (95% CI, 1.20-1.42).
      The area under the receiver operating characteristic curve was 0.83 (95% CI, 0.82
      0.85). The Hosmer-Lemeshow test showed that the difference between the mortality
      observed and the mortality predicted by Pediatric Index of Mortality 3 was
      statistically significant (chi, 135.63; p < 0.001). CONCLUSIONS: The Pediatric
      Index of Mortality 3 score adequately discriminated patients who died from those
      who survived in our population. However, the observed mortality was higher than
      predicted by the score. The use of an updated instrument such as Pediatric Index
      of Mortality 3 will allow an actual comparison between pediatric intensive care
      provided in the country and care provided internationally. This might also allow
      future planning of pediatric intensive care services in Argentina.

PMID- 30277896
TI  - Variability in Pediatric Ideal Body Weight Calculation: Implications for Lung
      Protective Mechanical Ventilation Strategies in Pediatric Acute Respiratory
      Distress Syndrome.
AB  - OBJECTIVES: No gold standard for ideal body weight determination in children
      exists. We aimed to compare four methods of ideal body weight calculation and
      determine level of agreement between methods and impact of measurement variance
      on tidal volumes prescribed in mechanically ventilated pediatric acute
      respiratory distress syndrome. DESIGN: Post hoc analysis of four multicenter
      pediatric acute respiratory distress syndrome studies. SETTING: Twenty-six
      academic PICUs. PATIENTS: Five hundred eighty-nine patients. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Ideal body weight was calculated by four common
      methods: National Center for Health Statistics, McLaren, Moore, and body mass
      index, and compared in three ways: 1) determine the proportion of the cohort for
      which each method could successfully calculate ideal body weight; 2) compare the
      level of agreement between the ideal body weight methods by Bland-Altman
      analysis; and 3) evaluate the difference in tidal volume when 6 mL/kg ideal body
      weight was prescribed. We a priori defined the better method to be one that could
      calculate ideal body weight in most subjects, had good agreement with other
      methods, and led to a lower tidal volume. Only 55% could have ideal body weight
      measured by all four methods. National Center for Health Statistics, McLaren, and
      Moore methods could calculate ideal body weight in greater than or equal to 90%,
      whereas body mass index method was successful in only 61% because of no body mass
      index validation in less than 2-year-olds. In comparing each method to the
      others, there was great variance, particularly in greater than or equal to 10
      year-olds. This variance was greatest between Moore and body mass index methods
      with greater than or equal to 10 kg difference in ideal body weight in some
      subjects. The McLaren method had the best agreement with all other methods, and
      yielded similar prescribed tidal volume in 2- to 10-year-olds and lower tidal
      volume in greater than or equal to 10 years old. CONCLUSIONS: There is
      substantial variation in calculated ideal body weight among four commonly used
      methods, particularly in adolescents. Since varying ideal body weight may lead to
      discrepancies in pediatric acute respiratory distress syndrome care, a standard
      approach to ideal body weight measurement is needed. We recommend the McLaren
      method to calculate ideal body weight in children with pediatric acute
      respiratory distress syndrome until a gold standard method is validated.

PMID- 30277898
TI  - A Case Report of Preeclampsia Causing Severe Hyponatremia: Rare or Rarely
      Reported?
AB  - Preeclampsia presenting as severe hyponatremia is an enigma of modern obstetric
      practice. The hyponatremia can cause severe maternal neurological morbidity,
      including cerebral edema and seizures. Neonates, with serum sodium reflecting
      maternal levels, are also at risk. Despite this, the literature remains ambiguous
      about its incidence, the pathophysiology is poorly understood, and guidelines on
      preeclampsia (including those of the American College of Obstetricians and
      Gynecologists) do not discuss the issue. This case of preeclampsia associated
      with severe hyponatremia in a laboring woman highlights these issues.

PMID- 30277899
TI  - Intraoperative Cell Salvage During Transurethral Resection of Prostate: A Case
      Report.
AB  - Intraoperative cell salvage (ICS) became commercially available in 1968 and has
      enjoyed wide uptake. However, its use in transurethral resection of prostate
      (TURP) remains rare. We describe a 71-year-old man who underwent TURP with
      incomplete blood cross-matching. He suffered significant hemorrhage requiring
      return to theater. There was great delay in obtaining appropriately cross-matched
      blood, due to previous alloimmunization. ICS was used to retrieve blood present
      in bladder irrigation. This is the first Australian report of ICS use during
      TURP. This case led to a change in our practice and serves to demonstrate the
      potential of this technology during emergencies.

PMID- 30277900
TI  - Treatment of Patellar Fractures and Injuries to the Extensor Mechanism of the
      Knee: A Critical Analysis Review.

PMID- 30277901
TI  - Native Adult Hip with Bacterial Septic Arthritis.

PMID- 30277902
TI  - Cardiorespiratory Fitness, Adiposity, and Heart Rate Variability: The CARDIA
      Study.
AB  - PURPOSE: The importance of cardiorespiratory fitness vs. adiposity in determining
      heart rate variability (HRV) is unclear. METHODS: From CARDIA, an observational
      cohort study, we included 2,316 participants (mean age 45.2+/-3.6 years at Year
      20, 57% female, 43% black) with HRV measured in 2005-06 (Year 20), and graded
      exercise test duration (GXTd) and adiposity measures (BMI, waist circumference)
      obtained in 1985-86 (baseline) and 2005-06. HRV measures (standard deviation of
      all normal RR intervals [SDNN] and square root of the mean of the squares of
      differences between all successive RR intervals [RMSSD]) were obtained from
      resting 30-second 12-lead ECGs. Cross-sectional associations between GXTd,
      adiposity and HRV were assessed at Year 20. Longitudinal changes in GXTd and
      adiposity measures were categorized as >=10% increase, <10% change (no change),
      or >=10% decrease. We used multivariable logistic regression to assess
      associations of GXTd and adiposity measures with unfavorable vs. more favorable
      HRV (lower 25th percentile vs. upper 75 percentile). RESULTS: A 1-SD increment in
      GXTd was associated with 22% and 32% lower odds of unfavorable SDNN and RMSSD,
      respectively; associations remained significant after adjustment for adiposity. A
      1-SD increment in adiposity measures was associated with 16-28% higher odds of
      unfavorable RMSSD; associations were not significant after adjustment for GXTd.
      Compared with no change/increase in GXTd, longitudinal decrease in GXTd was
      significantly associated with 55% and 94% higher odds of unfavorable SDNN and
      RMSSD, respectively, at Year 20. These associations remained significant after
      adjusting for adiposity. CONCLUSION: Cardiorespiratory fitness may be a stronger
      determinant of HRV than adiposity. Intervention studies are needed to better
      determine the differential effects of improved cardiorespiratory fitness vs.
      weight loss on HRV.

PMID- 30277903
TI  - Overview of Link Between Inflammatory Bowel Disease and Cardiovascular Disease.
AB  - Inflammation has been shown to play an increasingly important role in the
      pathogenesis of atherosclerosis and in precipitating thrombotic events.
      Inflammatory bowel disease (IBD) is a systemic inflammatory disorder with a wide
      range of extraintestinal manifestations including a clinically significant
      increase in the risk of venous thromboembolism compared to matched controls in
      several studies. The data for the association between IBD and ischemic heart
      disease are less clear; multiple population-based studies have shown both
      positive and negative associations between the 2 conditions. While the systemic
      inflammation should theoretically increase the risk for cardiovascular disease,
      inflammatory bowel also potentially provides a cardioprotective effect in several
      ways. Patients with IBD typically enter the healthcare system at an earlier age
      and experience a lower incidence of obesity, hypercholesterolemia, and
      hyperlipidemia. Given the complex interplay among the proatherogenic,
      prothrombogenic, and cardioprotective effects, IBD should be taken into
      consideration as a nontraditional risk factor for cardiovascular disease in
      specific subsets of patients.

PMID- 30277904
TI  - A Glutathione Precursor Reduces Oxidative Injury to Cultured Embryonic
      Cardiomyocytes.
AB  - BACKGROUND: Newborn infants are highly vulnerable to oxidative stress. Following
      birth asphyxia, oxidative injury due to ischemia-reperfusion can result in
      significant brain and heart damage, leading to death or long-term disability.
      STUDY QUESTION: The study objective was to evaluate the effectiveness of
      antioxidant gamma-L-glutamyl-L-cysteine (gammaGlu-Cys) in inhibiting oxidative
      injury to cultured embryonic cardiomyocytes (H9c2 cells). STUDY DESIGN: Control
      and gammaGlu-Cys-treated (0.5 mM) H9c2 cells were incubated under 6-hour ischemic
      conditions followed by 2-hour simulated reperfusion. MEASURES AND OUTCOMES: To
      quantify oxidative stress-induced apoptosis sustained by cardiomyocytes, lactate
      dehydrogenase (LDH) release and the presence of cytosolic cytochrome c were
      measured, as well as the number of secondary lysosomes visualized under electron
      microscopy. RESULTS: Compared to controls, H9c2 cells coincubated with gammaGlu
      Cys during ischemia-reperfusion exhibited a significant reduction in both LDH
      release into the incubation medium [23.88 +/- 4.08 (SE) vs. 9.95 +/- 1.86% of
      total; P = 0.02] and the number of secondary lysosomes [0.070 +/- 0.009 (SD) vs.
      0.043 +/- 0.004 per MUm; P = 0.01]. Inhibition of LDH release with gammaGlu-Cys
      was the same (P = 0.67) as that of a caspase inhibitor. The significant increase
      in cytosolic cytochrome c (P = 0.01) after ischemia-reperfusion simulation
      further supports gammaGlu-Cys's role in apoptosis prevention. CONCLUSIONS: It is
      concluded that the glutathione precursor gammaGlu-Cys protects cultured embryonic
      cardiomyocytes from apoptosis-associated oxidative injury.

PMID- 30277906
TI  - Mirtazapine for Major Depression Developed After Hyperemesis Gravidarum.

PMID- 30277905
TI  - Comparative Clinical Outcomes of Edoxaban in Adults With Nonvalvular Atrial
      Fibrillation.
AB  - BACKGROUND: A critical appraisal of all pooled evidence regarding novel oral
      anticoagulants (NOACs) for stroke prevention regardless of publication status or
      study design has not been conducted yet. Being the latest addition to NOACs, the
      data on edoxaban are especially scarce. STUDY QUESTION: What are the comparative
      clinical outcomes of edoxaban versus warfarin and other NOACs apixaban,
      dabigatran, or rivaroxaban in adults with nonvalvular atrial fibrillation? DATA
      SOURCES: Randomized controlled trials (RCTs), observational studies, and network
      meta-analyses were identified in PubMed, EMBASE, the Cochrane Library,
      Pharmapendium, Elsevier Clinical Pharmacology, and the clinicaltrials.gov trial
      registry in June 2018. STUDY DESIGN: Rapid review per a priori developed
      protocol, direct frequentist random-effects meta-analysis of aggregate data,
      grading the quality of evidence per the Grading of Recommendations Assessment,
      Development and Evaluation working group approach. RESULTS: Direct 4 RCTs (23,021
      patients) suggest that edoxaban is noninferior to warfarin in prevention of
      stroke and systemic embolism [pooled relative risk (RR): 0.65, 95% confidence
      interval (CI): 0.23-1.81, 2 RCTs] and reduces the risk of cardiovascular
      mortality (RR: 0.87, 95% CI: 0.78-0.97, 1 RCT), major cardiovascular morbidity
      (RR: 0.90, 95% CI: 0.82-0.98, 2 RCTs), and major bleeding events (RR: 0.80, 95%
      CI: 0.71-0.91, 1 RCT) but increases the risk of gastrointestinal bleeding (RR:
      1.21, 95% CI: 1.01-1.46, 1 RCT) and anemia (RR: 1.45, 95% CI: 1.05-1.99, 3 RCTs).
      Edoxaban is superior to warfarin in patients with increased risk of bleeding with
      warfarin because of variants in CYP2C9 and VKORC1 genes. Indirect evidence does
      not allow valid conclusions regarding comparative superiority of NOACs. The
      quality of evidence was downgraded because of reporting bias, small number of
      events, and indirectness in comparisons. CONCLUSIONS: Edoxaban is a welcome
      addition to the NOAC's armamentarium. However, the comparative data with other
      novel NOACs are mostly nonexisting, and urgently needed for better individual
      patient assessment.

PMID- 30277907
TI  - Thrombotic Microangiopathy and Acute Kidney Injury: Navigating the Differential
      Diagnosis.

PMID- 30277908
TI  - Melatonin Use in Psychiatry-Quo Vadis?
AB  - Melatonin use in clinical psychiatry is currently rife, and the trend of
      utilization is on the rise. Efficacy coupled with safety and lack of abuse
      potential render melatonin an attractive therapeutic option. Data from
      neuroscience accrue speaking to the idea of a pluripotent molecule beyond a mere
      sleeping aid. Here, authors would shed some light on melatonin use in psychiatry
      while examining the extant evidence.

PMID- 30277909
TI  - Immune Checkpoint Inhibitor-Associated Central Adrenal Insufficiency.

PMID- 30277910
TI  - Ultrasound Imaging for Complete Injury of the Posterior Interosseous Nerve After
      Forearm Surgery.

PMID- 30277911
TI  - Rehabilitation approach after surgical repair of spontaneous bilateral quadriceps
      tendon rupture in a healthy mason - a case report.
AB  - Quadriceps tendon rupture is a rare lesion, occurring most frequently in males
      over 60 years following a fall or trauma and associated with systemic diseases
      and risk factors. Bilateral injury is even more uncommon and disabling. The
      authors report a case of spontaneous bilateral quadriceps tendon rupture, non
      simultaneous (8 days apart), in a healthy 54-year-old Black male mason, that may
      be work-related. The patient was included in a 6-month rehabilitation program
      after surgical repair. Pain control and gait reacquisition were particularly
      difficult. Following the customized and phased rehabilitation program, the
      patient achieved the 6-month functional outcomes reported for unilateral rupture.
      The authors highlight the rehabilitation specificities and challenges of the
      bilateral lesion and discuss the pathophysiological role of prolonged periods of
      working in repetitive quadriceps overuse postures on quadriceps tendon rupture.

PMID- 30277913
TI  - Trifid Median Nerve-A Rare Variant in a Patient with Carpal Tunnel Syndrome.

PMID- 30277912
TI  - The Effectiveness of Group-based Physiotherapy-led Behavioral Psychological
      Interventions on Adults With Chronic Low Back Pain: A Systematic Review and Meta
      analysis.
AB  - Group-based physiotherapy-led behavioral psychological interventions (GPBPIs) are
      an emerging treatment for chronic low back pain (CLBP), but the efficacy of these
      interventions is uncertain. A review of relevant randomized controlled trials and
      a meta-analysis was conducted to evaluate the effectiveness of GPBPIs on pain
      relief in adults with CLBP. Literature databases, Google Scholar, bibliographies,
      and other relevant sources were searched. Thirteen (13) intervention studies
      published from 1998 to 2013 were included. The meta-analysis was conducted using
      RevMan software in accordance with the Cochrane Handbook for Systematic Reviews
      of Interventions. In reviewing the short term (< 6 months), intermediate (>=6 and
      <12 months) and longer term (>=12 months) effects of GPBPIs, long-term follow-up
      evaluations showed large and significant effect sizes (SMD = -0.25, 95%CI: -0.39
      to -0.11, I2= 38%, P<0.01). Subgroup analysis indicated that patients from GPBPIs
      group had the greater short, intermediate and long term pain reduction than
      patients on waiting listing or usual care group. Compared to other active
      treatments, GPBPIs showed a small but significant long term pain reduction in
      patients with CLBP (SMD = -0.18, 95%CI: -0.35 to -0.01, I2= 32%, P= 0.04). In
      general, GPBPIs may be an acceptable intervention to relieve pain intensity.

PMID- 30277914
TI  - An Unusual Pattern of Muscular Atrophy In A Case of GNE Myopathy Presenting with
      Low Back Pain.

PMID- 30277915
TI  - Visual Vignette: Isolated lesion of the fourth digit extensor muscle belly
      fascicle.

PMID- 30277916
TI  - Utilizing a Workshop Format for Physiatry Trainees in the Management of Acute
      Sports-Related Concussion.
AB  - Select residency and medical student training programs have developed and
      researched skill-based workshops, focusing on mastering a surgical or
      communication skill, however they are less frequently studied in physiatry
      residency programs. Given the importance of concussion care in physiatric
      practice, this study sought to measure the effectiveness of a novel sports
      related concussion workshop. Based on the 5 International Consensus Statement on
      Concussion in Sport, a six-hour concussion workshop was developed. Participants
      were administered a pre- and post-workshop questionnaire to gauge level of
      comfort managing various aspects of concussion, case-based questions to assess
      participant knowledge, and questions regarding satisfaction with workshop-based
      training sessions. 16 participants, ranging from PGY-2 to PGY-5, were included in
      the analyses, with significant gains (p < 0.0001 to p = 0.0045) made in all
      measures of comfort managing sports-related concussion; the study was unable to
      detect a statistically significant improvement in knowledge as assessed by the
      patient vignettes (p = 0.17), but participants did report high levels of
      satisfaction with workshop-based training sessions. Thus, workshop-based
      physiatry trainee education sessions can be employed to teach trainees certain
      skills, or provide comprehensive training in the management of a specific
      condition. Participants demonstrated improved comfort managing concussion, a
      trend towards improved knowledge, and a high degree of satisfaction with the
      content's method delivery.

PMID- 30277917
TI  - Letter to the Editor regarding Bilgilisoy Felix M, Kilic Z, Uckum A, et al:
      Mechanical Traction for Lumbar Radicular Pain: Supine or Prone? A Randomized
      Control Trial. Am J Phys Med Rehabil 2018;97:433-439.

PMID- 30277918
TI  - The struggle for evidence in physical and rehabilitation medicine: publication
      rate of randomized controlled trials and systematic reviews is growing more than
      in other therapeutic fields.
AB  - OBJECTIVE: To evaluate the rate of publication of randomized controlled trials
      (RCTs), systematic reviews and meta-analysis in Physical and Rehabilitation
      Medicine (PRM) and its variation over time. DESIGN: We performed a bibliometric
      study and searched PubMed from inception to 2017, using National Library of
      Medicine 3 level MeSH terms ("Rehabilitation", "Physical Therapy Modalities" and
      "Drug Therapy") and filters ("Randomized Controlled Trial", "Systematic Reviews"
      and "Meta-Analysis"). We used descriptive statistics and we calculated the best
      fitting regression model for all data considered. RESULTS: The absolute number of
      published papers is growing in rehabilitation as much as in other treatment
      fields such as drug therapy. While the rate of growth of publications for all
      studies relative to PubMed is bigger for drug therapies than for rehabilitation
      and physical therapy, the rate of growth of RCTs, systematic reviews and meta
      analysis is significantly greater for rehabilitation and physical therapy
      (P<0.001). In 2017, 19.3% and 28.2% of the total production of scientific
      articles for rehabilitation and physical therapy (respectively) was for RCTs and
      systematic reviews, versus 11.3% for drug therapy. CONCLUSION: Production of the
      highest form of research evidence (RCTs, systematic reviews and meta-analysis) is
      continuously increasing in PRM at a higher rate than in other treatment fields
      like drug therapy. The quality and results of this evidence should be evaluated
      in future studies.

PMID- 30277919
TI  - The association of an alpha2C adrenoreceptor gene polymorphism with vasomotor
      symptoms in African American women.
AB  - OBJECTIVE: The alpha2C adrenoreceptor deletion 322-325 (ADRA2C del 322-325)
      polymorphism has been associated with autonomic activity and thermoregulation,
      which are implicated in the vasomotor symptom (VMS) mechanism. The ADRA2C del
      (322-325) has higher prevalence in African American women, a group known to
      experience more frequent and bothersome VMS. We assessed whether the ADRA2C del
      (322-325) genotype is associated with increased frequency of VMS in African
      American women. METHODS: DNA samples from African American (N = 400) women
      participating in the Study of Women's Health Across the Nation (SWAN) were
      genotyped for the ADRA2C del (322-325) polymorphism. Longitudinal data on VMS
      were obtained from the SWAN repository. The relation of ADRA2C del (322-325)
      genotypes (deletion/deletion [D/D]; insertion/deletion [I/D]; insertion/insertion
      [I/I]) with VMS over the menopausal transition for up to 12 years of follow-up
      was examined using generalized estimating equations. Primary models considered
      the outcome of frequent VMS (6 or more days in the prior 2 wk vs VMS <6 d in the
      prior 2 wk) by stage of menopause. RESULTS: Four hundred DNA samples from African
      American women were included. Seventy-five women (18.8%) were found to carry the
      homozygous variant allele (D/D). There was no significant difference in the
      trajectory of frequent VMS over the menopausal transition between women with D/D
      and I/I + I/D genotypes (P = 0.39). CONCLUSIONS: In this preliminary study among
      African American women in SWAN, ADRA2C del (322-325) was not significantly
      related to self-reported VMS. Further studies are warranted to help us understand
      the role of the adrenergic system in the physiology of VMS to tailor medical
      therapy to patient needs.

PMID- 30277920
TI  - Age and leptinemia association with anxiety and depression symptoms in overweight
      middle-aged women.
AB  - OBJECTIVE: The aim of the study was to investigate the effect of menopause and of
      postmenopausal stages on depression and anxiety symptoms, and whether these
      symptoms associate with anthropometric, metabolic, and hormonal parameters in
      midlife women. METHODS: Postmenopausal women (age 50-65), either at early (EPM,
      n=33) or late (LPM, n = 23) postmenopause, and 23 premenopausal controls (PreM,
      age 40-50), matched for BMI with the PM groups, were studied. Blood biochemical
      and hormonal determinations, bioimpedance anthropometry, and depression and
      anxiety symptoms (Beck's depression [BDI] and anxiety [BAI] inventories) were
      conducted. RESULTS: The BAI score was higher in both PM groups than in the PreM
      group. In contrast, only the LPM group showed a significantly elevated BDI score.
      All groups presented overweight and abdominal obesity, having similar BMI and
      waist/hip ratio values. Both PM groups showed insulin resistance, whereas only
      the LPM group presented decreased skeletal muscle mass and basal metabolic rate.
      Correlation analysis, including all 79 middle-aged women, showed age, percentage
      body fat, waist/hip ratio, and leptinemia to correlate positively with the
      anxiety and depression scores. Multivariate regression showed leptin and age to
      associate positively with depressive- and anxious-like symptoms. CONCLUSIONS:
      Postmenopausal women presented impaired body composition, energy expenditure,
      insulin sensitivity, and mental symptoms, in comparison to similarly overweight
      premenopausal women. Among all the overweight midlife women, these symptoms were
      more strongly associated with age and leptin levels than with reproductive aging
      itself. The data indicate that, among overweight middle-aged women with abdominal
      obesity, the aging process and the development of leptin resistance are
      associated with impairment of mental health.

PMID- 30277921
TI  - Effect of high-intensity interval training on body composition and inflammatory
      markers in obese postmenopausal women: a randomized controlled trial.
AB  - OBJECTIVES: This study tested whether high-intensity interval training is a time
      efficient strategy for improving visceral adiposity tissue and inflammatory
      markers in obese postmenopausal women when compared with combined training.
      Moreover, we tested whether change in visceral adiposity tissue is associated
      with alterations in these inflammatory markers. METHODS: Postmenopausal women
      were randomized in two groups: combined training (n = 13) and high-intensity
      interval training (n = 13). The combined training group performed 60 minutes of
      walking at 70% of maximum heart rate and resistance exercises at 70% of one
      repetition maximum. The high-intensity interval training group performed 28
      minutes of high-intensity exercises (> 80% of maximum heart rate). Both groups
      trained three times a week for 12 weeks. Body composition and inflammatory
      markers were analyzed with dual-energy x-ray absorptiometry scanning and enzyme
      linked immunosorbent assay, respectively. RESULTS: All groups reduced body fat
      percentage (P = 0.026), visceral adiposity tissue (P = 0.027), leptin (P =
      0.043), and increased interleukin (IL)-1 receptor antagonist (P < 0.01). The high
      intensity interval training group reduced visceral adiposity tissue (P = 0.021)
      in a greater magnitude and increased interleukin-6 (P = 0.037) level when
      compared with the combined training group. Moreover, the visceral adiposity
      tissue changes explained the changes in IL-6 (56%; P = 0.002) only in the high
      intensity interval training group. CONCLUSIONS: These results suggest that high
      intensity interval training is a time-efficient strategy for improving visceral
      adiposity tissue and inflammatory markers in obese postmenopausal women.
      Moreover, we observed that serum cytokine changes, at least in part, depend on
      visceral adiposity tissue alterations.

PMID- 30277922
TI  - To the Editor.

PMID- 30277923
TI  - Optimal evaluation for suspected coronary artery disease: does the initial test
      matter?

PMID- 30277924
TI  - Cardiac shock wave therapy for refractory angina: angiogenesis, placebo effects,
      and randomized trial designs.

PMID- 30277925
TI  - Optometric Research Summit: 2018.

PMID- 30277926
TI  - A noninvasive indicator for the diagnosis of early hepatitis B virus-related
      liver fibrosis.
AB  - BACKGROUND AND AIMS: Liver stiffness measurement (LSM) detected by FibroScan,
      combined with biochemical indexes, has shown potential values for assessment of
      liver fibrosis pathological degrees. Here we aimed to investigate a noninvasive
      method for hepatitis B virus-related liver fibrosis. PATIENTS AND METHODS: In
      all, 307 patients who underwent liver biopsy and LSM measurement were included.
      Inflammation grades and fibrosis stages were evaluated according to METAVIR
      scoring system. Spearman's rank correlation analysis, logistic regression
      analysis, and receiver operating characteristic (ROC) curves analysis were
      performed to assess the factors' role in inflammation grades/fibrosis stages.
      RESULTS: Spearman's rank correlation analysis showed that LSM, alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), and AST-to-platelet
      ratio index were positively correlated with inflammation grades and histologic
      fibrosis stages; platelets showed negative correlation, and AST-to-ALT ratio was
      not related. Logistic regression analysis indicated that LSM and APRI were risk
      factors for inflammation grades; LSM was the independent risk factor for fibrosis
      stages, P<0.0001, odds ratio>1. ROC curve analysis found LSM cutoff values and
      areas under the curve for the diagnosis of fibrosis scores: 6.95 and 0.804,
      respectively, for the diagnosis of significant fibrosis (F>=F2); 10.35 and 0.856,
      respectively, for severe fibrosis (F>=F3); 11.35 and 0.897, respectively, for
      cirrhosis (F=F4). Considering ALT as a confounding factor, ROC analysis was
      repeated in patients with normal and elevated ALT separately; the results
      indicated that when ALT was up to 40 U/l, LSM cutoff value and areas under the
      curve for the diagnosis of significant fibrosis (F>=F2) were 6.55 and 0.748,
      respectively. CONCLUSION: This study provided a noninvasive treatment and
      prevention indicator for early hepatitis B virus-related liver fibrosis.

PMID- 30277927
TI  - Vulvar Edema as Presenting Complication of Simultaneous Pancreas-Kidney
      Transplantation With Bladder Drainage.

PMID- 30277929
TI  - Genetic factors involved in the bioavailability of tomato carotenoids.
AB  - PURPOSE OF REVIEW: To provide an update on the genetic factors recently
      associated with the interindividual variability of tomato carotenoid
      bioavailability. RECENT FINDINGS: Several clinical studies have demonstrated that
      the main carotenoids found in tomatoes (lycopene, phytoene, phytofluene, beta
      carotene, lutein) all display relatively large interindividual variabilities of
      their bioavailability, with coefficients of variations more than 70%. The
      bioavailability of the parent molecules, and the blood/tissue appearance of their
      metabolites, is modulated by numerous proteins, involved in intestinal absorption
      and metabolism, blood lipoprotein transport or tissue uptake. Several single
      nucleotide polymorphisms (SNPs) have been associated with the interindividual
      variability of lycopene, lutein and beta-carotene bioavailability, with six genes
      consistently shared between the three carotenoids, and in particular one SNP in
      ELOVL fatty acid elongase 2. The effects of the genetic variants taken separately
      are relatively low, that is each variant is usually associated with only a few
      percentage of the variability but multivariate analyses suggest that the additive
      effect of several genetic variants can explain a significant fraction of tomato
      carotenoid bioavailability. SUMMARY: Additional studies are needed to improve our
      knowledge of the genetic determinants of tomato carotenoid bioavailability but
      progress in this field could one day allow nutritionists to provide more
      personalized dietary recommendations.

PMID- 30277930
TI  - Identifying and Treating Opioid Side Effects: The Development of
      Methylnaltrexone.
AB  - : Methylnaltrexone Reverses Chronic Opioid-induced Constipation: A Randomized,
      Controlled Trial. By Yuan CS, Foss JF, O'Connor M, Osinski J, Karrison T, Moss J,
      Roizen MF. JAMA 2000; 283:367-72. Reprinted with permission. CONTEXT:
      Constipation is the most common chronic adverse effect of opioid pain medications
      in patients who require long-term opioid administration, such as patients with
      advanced cancer, but conventional measures for ameliorating constipation often
      are insufficient. OBJECTIVE: To evaluate the efficacy of methylnaltrexone, the
      first peripheral opioid receptor antagonist, in treating chronic methadone
      induced constipation. DESIGN: Double-blind, randomized, placebo-controlled trial
      conducted between May 1997 and December 1998. SETTING: Clinical research center
      of a university hospital. PARTICIPANTS: Twenty-two subjects (9 men and 13 women;
      mean [SD] age, 43.2 [5.5] years) enrolled in a methadone maintenance program and
      having methadone-induced constipation. MAIN OUTCOME MEASURES: Laxation response,
      oral-cecal transit time, and central opioid withdrawal symptoms were compared
      between the 2 groups. RESULTS: The 11 subjects in the placebo group showed no
      laxation response, and all 11 subjects in the intervention group had laxation
      response after intravenous methylnaltrexone administration (P<.001). The oral
      cecal transit times at baseline for subjects in the methylnaltrexone and placebo
      groups averaged 132.3 and 126.8 minutes, respectively. The average (SD) change in
      the methylnaltrexone-treated group was -77.7 (37.2) minutes, significantly
      greater than the average change in the placebo group (-1.4 [12.0] minutes;
      P<.001). No opioid withdrawal was observed in any subject, and no significant
      adverse effects were reported by the subjects during the study. CONCLUSIONS: Our
      data demonstrate that intravenous methylnaltrexone can induce laxation and
      reverse slowing of oral cecal-transit time in subjects taking high opioid
      dosages. Low-dosage methylnaltrexone may have clinical utility in managing opioid
      induced constipation.

PMID- 30277931
TI  - Lung-protective Ventilation in the Operating Room: Individualized Positive End
      expiratory Pressure Is Needed!

PMID- 30277932
TI  - Positive End-expiratory Pressure and Mechanical Power.
AB  - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW:
      BACKGROUND:: Positive end-expiratory pressure is usually considered protective
      against ventilation-induced lung injury by reducing atelectrauma and improving
      lung homogeneity. However, positive end-expiratory pressure, together with tidal
      volume, gas flow, and respiratory rate, contributes to the mechanical power
      required to ventilate the lung. This study aimed at investigating the effects of
      increasing mechanical power by selectively modifying its positive end-expiratory
      pressure component. METHODS: Thirty-six healthy piglets (23.3 +/- 2.3 kg) were
      ventilated prone for 50 h at 30 breaths/min and with a tidal volume equal to
      functional residual capacity. Positive end-expiratory pressure levels (0, 4, 7,
      11, 14, and 18 cm H2O) were applied to six groups of six animals. Respiratory,
      gas exchange, and hemodynamic variables were recorded every 6 h. Lung weight and
      wet-to-dry ratio were measured, and histologic samples were collected. RESULTS:
      Lung mechanical power was similar at 0 (8.8 +/- 3.8 J/min), 4 (8.9 +/- 4.4
      J/min), and 7 (9.6 +/- 4.3 J/min) cm H2O positive end-expiratory pressure, and it
      linearly increased thereafter from 15.5 +/- 3.6 J/min (positive end-expiratory
      pressure, 11 cm H2O) to 18.7 +/- 6 J/min (positive end-expiratory pressure, 14 cm
      H2O) and 22 +/- 6.1 J/min (positive end-expiratory pressure, 18 cm H2O). Lung
      elastances, vascular congestion, atelectasis, inflammation, and septal rupture
      decreased from zero end-expiratory pressure to 4 to 7 cm H2O (P < 0.0001) and
      increased progressively at higher positive end-expiratory pressure. At these
      higher positive end-expiratory pressure levels, striking hemodynamic impairment
      and death manifested (mortality 0% at positive end-expiratory pressure 0 to 11 cm
      H2O, 33% at 14 cm H2O, and 50% at 18 cm H2O positive end-expiratory pressure).
      From zero end-expiratory pressure to 18 cm H2O, mean pulmonary arterial pressure
      (from 19.7 +/- 5.3 to 32.2 +/- 9.2 mmHg), fluid administration (from 537 +/- 403
      to 2043 +/- 930 ml), and noradrenaline infusion (0.04 +/- 0.09 to 0.34 +/- 0.31
      ug . kg . min) progressively increased (P < 0.0001). Lung weight and lung wet-to
      dry ratios were not significantly different across the groups. The lung
      mechanical power level that best discriminated between more versus less severe
      damage was 13 +/- 1 J/min. CONCLUSIONS: Less than 7 cm H2O positive end
      expiratory pressure reduced atelectrauma encountered at zero end-expiratory
      pressure. Above a defined power threshold, sustained positive end-expiratory
      pressure contributed to potentially lethal lung damage and hemodynamic
      impairment.

PMID- 30277936
TI  - Article Summaries for October 2018 Psychosomatic Medicine, Volume 80, Issue 8.

PMID- 30277935
TI  - Chronic obstructive pulmonary disease and sleep: an update on relevance,
      prevalence and management.
AB  - PURPOSE OF REVIEW: Despite the importance of sleep in patients with COPD, this is
      frequently left unassessed in clinical practice. This review is intended to
      highlight the inter-relationship between COPD and sleep with an overview of the
      underlying pathophysiology and symptom burden followed by a review of the current
      management. RECENT FINDINGS: Recent data has indicated that specific respiratory
      support provided to patients with COPD and sleep disordered breathing improves
      clinical outcomes. The provision of respiratory support has expanded from
      established noninvasive ventilation and continuous positive airway pressure
      therapy to include novel interventions such as nasal high flow therapy. Sleep is
      impacted in many ways in patients with COPD and this poor sleep quality can be
      shown to be associated with worse clinical outcomes. Although data to support a
      causal effect is lacking, there is increasing interest in interventions such as
      cognitive behavioural therapy to improve patient symptom burden. SUMMARY:
      Clinicians managing patients with COPD should be alert to and actively elicit
      symptoms of comorbid sleep disorders. Once diagnosed, these sleep disorders
      should be actively managed in line with best practice. Research should focus on
      whether the active management of sleep disturbance improves long-term outcomes in
      COPD.

PMID- 30277937
TI  - Epithelioid Hemangioma of the Face.
AB  - An epithelioid hemangioma is a very rare lesion arising from vascular structures.
      We encountered 2 cases in atypical locations, one in the orbital and the other in
      the nasal region. We performed preoperative angiography in addition to the
      diagnostic imaging recommended in the literature. Angiography highlighted the
      lesions well, and in one case, it was possible to embolize the arterial trunk of
      a high-flow lesion. Angiography underscored how such lesions may differ from the
      vascular perspective, emphasizing the importance of histology in correct
      diagnosis. Management of both hemangiomas yielded good functional and cosmetic
      outcomes with no disease recurrence.

PMID- 30277938
TI  - Anthropometric Evaluation of Periorbital Region and Facial Projection Using Three
      Dimensional Photogrammetry.
AB  - INTRODUCTION: Direct anthropometric and three-dimensional (3D) photogrammetry
      measurements have been used extensively in cleft/craniofacial surgery to assess
      morphological changes and surgical outcomes. Craniofacial procedures alter the
      sagittal projection of periorbital bony prominences. Mulliken described a method
      of measuring their projection relative to the corneal plane but is impractical in
      clinical practice. Three-dimensional photogrammetry may offer a solution;
      however, the cornea is not visualized on this. The authors propose to develop new
      normative measurements of facial projection relative to the pupil. METHODS: Five
      3D photographs were taken of 5 individuals using Vectra M5 camera. Facial
      projection measurements were taken of the sagittal projection of the bilateral
      periorbital landmarks and nasal radix relative to the pupil using Mirror 3D
      analysis. Standard deviations (SD) were determined for each subject and
      laterality. Chi-square tests confirmed all SD <1 mm. Intra and inter-rater
      reliability were confirmed with an intraclass correlation coefficient assessment.
      RESULTS: Three male and 2 female subjects were photographed with 5 unique images.
      Standard deviations of repeat measures of all landmarks were <0.5 mm. Chi-square
      tests confirmed with statistical significance that SD for all values except for
      the radix was <1 mm (P<0.05). Intrarater reliability was high for all landmarks
      (intraclass correlation coefficient coefficients 0.93-0.99). Inter-rater
      reliability was good for the lateral canthi and excellent for all others.
      CONCLUSION: This technique demonstrates repeatability with high reliability on
      serial photographs and is applicable to measuring surgery effects and growth on
      facial projection. Establishment of age-specific normative values for landmark
      projection will refine usage applicability in operative planning.

PMID- 30277939
TI  - Study on Hair Distribution in Healthy Males for Hair Restoration Design.
AB  - BACKGROUND: The incidence of hair loss among Chinese male has increased to 21.3
      per hundred. Hair restoration has been an effective technique. Detailed hair
      distribution has a tremendous impact on the surgery design. OBJECTIVE: To
      investigate the pattern of hair distribution in Chinese young adult males.
      METHODS: A total of 1000 males without hair disease were enrolled. We evaluated
      the locations of the main anatomical marks at different sites on the scalp and
      analyzed the hair density and follicular unit structure using the standard
      photographs and trichoscope. RESULTS: The hairline shapes were classified as:
      linear (48.7%), linear with central protrusion (27.9%), round (9.8%), round with
      central protrusion (13.7%). The average height of the median line was 6.78 +/-
      0.75 cm, the ratio of the median line and the forehead height was 0.333. The
      average distance from the parietal whorl to the vertical bimeatal line was 7.05
      +/- 3.32 cm, and most of the PWs were on the right (51.4%) and had a clockwise
      pattern (73.3%). The hair density was 171.12 +/- 18.32 hairs/cm in the vertex. 1
      hair follicular units were (75.90% and 56.39%) in anterior hairline and temporal
      area. CONCLUSION: Our study clearly assisted understanding of scalp anatomy and
      hair distribution in Chinese young adult males.

PMID- 30277940
TI  - Optic Disc Deformation and Orbital Bone Erosion Secondary to a Huge Neglected
      Orbital Cavernous Hemangioma.
AB  - Cavernous hemangioma (CH) is the most common benign tumor of the orbit which can
      expand the bony orbit by gradual growth of a large tumor. In this article, the
      authors report a 28-year-old man presented with a longstanding unilateral
      proptosis secondary to a huge orbital CH which also caused optic disc deformation
      and bone erosions in the adjacent orbital walls. The optic disc deformities
      resolved after the tumor removal.

PMID- 30277941
TI  - Osteotomy in Genioplasty by Piezosurgery.
AB  - BACKGROUND: The chin is the most prominent and median sector of the lower third
      of the face giving harmony to nose and lips. The authors present the application
      of piezoelectric scalpel for the correction of different chin deformities. The
      distinctive characteristics of this device allow the authors to avoid or reduce
      the immediate genioplasty complications. METHODS: Fifty-five patients of
      defective chin have been treated from January 2006 to April 2008. Intraoral
      genioplasty was performed during the correction of dentofacial dysmorphisms or
      associated with nasal surgery. The authors used a piezoelectric cutting device to
      perform different osteotomies and if necessary, interpositional graft was used to
      stabilize bony segments. RESULTS: Piezosurgery has been associated with a fewer
      number of postoperative complications, especially as regard intraoperative
      bleeding, nerve injuries (immediate and late), hematomas and seromas, asymmetry
      (immediate and early). The mean time for completing the complete procedure of
      genioplasty with piezosurgery was almost the same compared with the saw and
      drill. CONCLUSION: Genioplasty represents one of the most common ancillary
      procedures and may be associated with corrective surgery of dentofacial
      dysmorphisms. Mental nerve injuries, asymmetries, intraoperative bleeding are the
      main immediate complications of genioplasty. Distinctive characteristics of
      ultrasonic piezoelectric osteotomy are selective cut of mineralized structure
      with less risk of vascular and nervous damage (microvibrations), intraoperative
      precision (thin cutting scalpel and no macrovibrations), blood free site
      (cavitation effect). In the authors' experience, piezoelectric scalpel, compared
      with saw and drill, enables them to reduce or avoid immediate complications of
      chin surgery, helping the surgeon to reach patients' satisfaction.

PMID- 30277942
TI  - Intracorporeal Septorhinoplasty: Technique and Outcome.
AB  - OBJECTIVE: Septal deformities usually associated with functional and aesthetic
      nasal consequences. Multiple techniques were described to correct these
      deformities. Using less invasive and at the same time competent technique with
      loge standing results is important. This study aimed to assess intracorporeal
      correction for septal deviation with assessment of its competence in managing
      deferent degrees of deviation and to show concomitant patient-dependant internal
      valve manipulation used. METHODS: Intracorporeal correction of septal deviation
      was used in 35 patients which was performed at plastic surgery departments of
      Menoufia University Hospital and Mawada Privet Hospital, Egypt. The study was
      carried out between July 2014 and July 2017. RESULTS: Thirty-five patients with
      variable types of septal deformities, 16 of them were females and 19 were males,
      were included in the study. Age of patients was between 18 and 55 years (mean
      24.9, standard deviation 7.9). Etiology was found as follows: 15 (about 43%)
      posttraumatic septal deviation, 8 (about 23%) patients had postcleft septal
      deviation, and the remaining 12 had idiopathic septal deviation. Spreader graft
      was in 22 (about 63%) patients. Septal hematoma followed by septal perforation
      occurred in 1 patient (2.8%), while dorsal irregularities were found in 3 (8.4%)
      patients. Recurrent septal deviation occurred in 2 (5.6%) patients. Concerning
      functional outcome, no residual nasal obstruction was found in all patients with
      negative Cottle sign postoperative. CONCLUSION: Intracorporeal correction of
      septal deformities in open rhinoplasty technique is still found to be effective
      and less invasive option even with sever septal deviation.

PMID- 30277943
TI  - Congenital Cleft Earlobe: Technique for Repair of a Triple-Lobe Type Defect.
AB  - Congenital cleft earlobe is a rare clinical entity that results from failure of
      fusion during embryologic development. In contrast to acquired earlobe clefts,
      congenital defects are usually associated with tissue loss, thereby complicating
      surgical repair. The authors present the case of a 22-year-old female with a
      triple-lobe type of congenital cleft earlobe and discuss their technique for
      repair.

PMID- 30277944
TI  - A New Technique for Sagittal Synostosis: A Plurality of Small Incisions Minimally
      Invasive Technique Used on Infants and Young Patients.
AB  - OBJECTIV: The authors devised a multiple small incisions minimally invasive
      technique for use in isolated nonsyndromic sagittal synostosis to achieve better
      esthetic effect and satisfactory reshaping of the calvarial vault. The purpose of
      this study is to provide clinicians with new and feasible solution. METHODS: From
      April 2016 to January 2017, 5 male patients were successfully treated with
      minimally invasive surgery. The age ranges from 1.5 to 3.3 years. The authors
      designed 9 short skin linear incisions (2-3 cm long) strategically to disperse in
      the scalp. The patient was assessed in a series including sex, age of surgery,
      blood loss, blood transfusion, duration of surgery, postoperative complications,
      preoperative and postoperative cephalic index (CI), length of stay (LOS),
      esthetic outcomes, and intellectual developmental quotient (DQ). RESULTS: The
      shortest operation time is 1.5 hours. The shortest hospital stay is 6 days. The
      blood loss ranged from 135 to 280 mL. No serious complications occurred during
      the follow-up time. Postoperative 3-dimensional CT scan showed that the extensive
      floating bone formed well. Preoperative CI ranged from 64.2 to 68 and
      postoperatively 69.4 to 74.3. Mental development was tested by children heath
      care practioners, significantly improving DQ from 67 to 81 preoperatively and 76
      to 90 postoperatively. All children receive good esthetic results. CONCLUSION:
      The new technique is safe and effective. The advantages are satisfactory:
      calvarial fornix remodeling, less visible appearance of scars, shorter length of
      surgery, lower mental and financial stress, optimal age for surgery, no
      endoscopic adjuvant and postoperative helmet are needed.

PMID- 30277945
TI  - Evaluation of a Sample of Patients With Unilateral Cleft Lip and Palate Treated
      With a Two-Stage Protocol.
AB  - The aim of this paper was to assess growth, speech, and aesthetic results at the
      completion of growth in patients with unilateral cleft lip and palate treated
      with the 2 stages Milan surgical protocol.Craniofacial growth was evaluated with
      cephalometric analysis and a theoretical need for orthognathic surgery.Nasolabial
      appearance was qualitatively assessed using the Asher McDade Aesthetic
      Index.Speech was assessed using the Gos.Sp.Ass '98 modified for Italian language
      scoring system.Burden of care was recorded in terms of number of secondary
      surgical procedures. All of the patients were treated and evaluated at San Paolo
      Hospital, Smile House, Milan.Fifty-two consecutive patients treated by the same
      surgeon were recalled, 12 patients did not come for assessment.The first surgical
      step (average age of 6 months) was cheilorhinoplasty (Millard modified Delaire
      technique) and soft palate rapair (Pigott). The second step (average age of 35
      months) was hard palate and alveolar repair performed simultaneously with an
      early secondary gengivo alveolo plasty. Fifty-six percent of the patients did not
      need further surgery after the 2-stage surgery protocol.The 2-stage surgical
      protocol of Milano, Smile House, seems to be effective for treatment of
      unilateral cleft lip and palate, with good results in terms of speech, labial
      appearance, and alveolar cleft management. Nevertheless, maxillary growth was
      moderately impaired by the protocol.

PMID- 30277946
TI  - Microsurgical Treatment of Ruptured True Posterior Communicating Artery Aneurysm
      in the Distal Portion of the Posterior Communicating Artery.
AB  - The true posterior communicating artery (PCoA) aneurysms in the distal portion of
      the posterior communicating artery are rare. The authors describe a 63-year-old
      woman with 1 true PCoA aneurysms in the distal portion of the PCoA, which was
      treated surgically through modified pterional approach. No neurologic deficit was
      present at the postoperative period. Although endovascular intervention is more
      and more widely used in the treatment of aneurysms, the authors have also
      emphasized that true PCoA aneurysms in the distal portion of the PCoA can also be
      surgically treated in suitable patients.

PMID- 30277947
TI  - Can Volumetric and Morphological Variants of Sphenoid Sinuses Influence Sinuses
      Opacification?
AB  - Improvements in computed tomography and in functional endoscopic sinus surgery
      have recently increased interest toward paranasal sinus anatomy and anatomic
      variations that can be observed in patients affected by sinusitis. Isolated
      sphenoid sinusitis is a relatively rare pathology, often related to nonspecific
      symptoms, therefore making diagnosis difficult. The correlation between this type
      of sinusitis and anatomical variants remains unclear.The authors' aim was to
      retrospectively revise paranasal sinuses computed tomography scans of patients
      affected by sphenoid sinusitis, compared with a control group, analyzing the
      types of sphenoid sinus and the presence of aberrant pneumatization, and
      performing a segmentation of the sphenoid sinuses to calculate the
      volumes.Sphenoid sinuses of 60 patients affected by sinus opacification, compared
      with a control group, were segmented. Type of sinus (sellar, presellar,
      postsellar) and presence of aberrant pneumatization were assessed as well.
      Possible statistically significant differences in volumes according to sex and
      group were assessed through 2-way ANOVA test (P < 0.05). Post-hoc test was
      assessed through Student t test. chi test was applied in order to verify the
      statistically significance of differences in frequency of different types of
      sinus pneumatization variants (P < 0.05).Average volume of sphenoid sinuses in
      males was of 7.672 cm and of 7.751 cm in females within the group of patients;
      statistically significant differences in volume were found according to sex (P:
      0.342), but not between the patients and control group (P: 0.0929). Post-hoc test
      verified that males affected by sinus opacification showed smaller volumes in
      comparison with the control males (P < 0.05). In addition, patients by affected
      sinus opacification showed more frequently the postsellar type and were less
      affected by pneumatization variants of the sphenoid bone than the control group
      (P < 0.05).This study first suggests the possible protective role of variants of
      pneumatization in the development of sphenoid sinus opacification.

PMID- 30277948
TI  - Reconstruction of Wegener Granulomatosis Nose Deformity Using Fascia Lata Graft.
AB  - Wegener granulomatosis (WG) is a necrotizing vasculitis that involves the upper
      respiratory tract, the lungs, and the kidneys. It also causes deformities of the
      nose in practically all patients, altering the cartilaginous and bony structure
      as well as the inner lining of the nose.The surgical repair of these nasal
      distortions is a challenge mainly due to the impairment of wound healing and
      graft take that is caused both by the disease itself and by the prolonged
      immunosuppressant treatment.Many different reconstruction plans have been
      developed, using costal or calvarial bone grafts, cartilage grafts and local skin
      and mucosa flaps. Results have been diverse.The authors present the case of a 56
      year-old patient who suffered from WG and consulted for nasal sequelae. She
      initially underwent several failed attempts at reconstruction; finally, the
      authors performed a nasal repair using a double strip of fascia lata as a dorsal
      graft, with no complications and a good aesthetic result.Fascia lata graft is a
      new and good option for nasal reconstruction in patients with WG because it is
      easily obtainable, it can be set in place through closed rhinoplasty and it can
      achieve good vascularization with low risk of resorption or disease reactivation.

PMID- 30277949
TI  - Incidence of Foramen Tympanicum (of Huschke): Comparing Cadaveric and Radiologic
      Studies.
AB  - PURPOSE: The foramen tympanicum (FT) represents a developmental anomaly that
      forms due to incomplete fusion of processes of the tympanic ring. Its presence in
      the population is controversial and it has been associated with a number of
      otologic complications. The aim of this study was to systematically analyze the
      prevalence, anatomical characteristics, and ethnic variations of the FT and
      compare these parameters in cadaveric and radiologic studies. METHODS: An
      extensive search was conducted through the major electronic databases, and
      identified articles were separated into 2 groups based on their methodology:
      cadaveric and radiologic studies. Data extracted included study modality,
      prevalence data, ethnicity, gender, side, laterality, and diameter. RESULTS: A
      total of 8 studies (n = 2671 patients) were included into our meta-analysis. The
      main findings revealed that the prevalence of the FT in the population is 14.9%,
      it is more often unilateral (62.5%) than bilateral (37.5%), it is most often
      reported in Asia (21.4%), and it is more prevalent in cadavers (21.2%) than in
      radiologic studies (8.8%) (not statistically significant). CONCLUSION: As the FT
      is present in more than one-tenth of the population, it is important to consider
      the possibilities of its presence when undertaking surgical procedures in the
      temporomandibular joint and ear region and plan accordingly to avoid injuries.
      Clinicians should keep it as one of the possible diagnoses while confronted with
      patients presenting with otologic complications. The use of newer imaging
      techniques was recommended, such as cone-beam computer tomography to detect the
      FT prior to surgery.

PMID- 30277950
TI  - Maxillary Alveolar Ridge Atrophy Reconstructed With Autogenous Bone Graft
      Harvested From the Proximal Ulna.
AB  - Atrophy of the alveolar ridge requires bone grafting at the implant site for
      rehabilitation of the masticatory function with dental implants. Despite the
      advances in the development of bone substitutes, autogenous bone graft remains
      the "criterion standard" because of its osteogenic, osteoinductive,
      osteoconductive potential, and non-immunogenic properties. However, harvesting of
      autogenous bone is not exempt from donor site morbidity. In this context, the use
      of autogenous bone derived from the proximal ulna might be a viable resource to
      obtain corticocancellous bone graft, as the harvesting from this donor site is
      associated with low morbidity. Thus, this article aimed to describe a case in
      which a maxillary sinus floor augmentation was performed by means of autogenous
      bone graft harvested from the proximal ulna, as the donor site. An appositional
      bone block graft harvested from the same region was used to augment the residual
      alveolar ridge. Clinically, healing proceeded uneventfully with no major
      complications. After 8 months, a proper amount of bone was found at the implant
      site, allowing a prosthetically driven implant insertion and subsequent implant
      supported rehabilitation. Results were clinically and radiographically stable
      after a 3-year follow-up. The present case report suggested that proximal ulna as
      a donor site should be considered as a safe and reliable alternative for alveolar
      ridge augmentation. Besides the case presentation, a comprehensive review of the
      literature was also provided.

PMID- 30277951
TI  - Novel Application of Platelet-Rich Fibrin as a Wound Healing Enhancement in
      Extraction Sockets of Patients Who Smoke.
AB  - The objectives of this study were to assess the potential of platelet-rich fibrin
      (PRF) on acceleration of soft tissue healing after tooth extraction and to
      evaluate its effectiveness in reducing the prevalence of dry socket among smoker
      patients. Twenty smoker male patients aged (18-72) years with multiple teeth
      extraction were participated in this clinical research. They underwent trans
      alveolar extraction of 40 teeth. The extraction sockets were divided in each
      patient into 2 groups: the study group in which extraction sockets were treated
      with PRF and the control group: in which extraction sockets left to heal
      naturally without PRF. Platelet-rich fibrin enhanced soft tissue healing and
      reduced inflammatory process within the study group compared with control group
      as the 2-tailed P value equaled 0.0035 which was very statistically significant.
      Pain level according to visual analog scale in control group had average of
      (1.8), while in the study group had average of (0.65) and the P value equaled
      0.1511 which was not statistically significant. Degree of epithelization was
      recorded by dental caliper for both groups and the 2-tailed P value equaled
      0.7134 which was insignificant. The results from this study showed that PRF
      enhanced the quality of soft tissue healing of extraction socket among smoker
      patients but it did not show significant difference regarding pain reduction, dry
      socket prevention, and socket closure. Future clinical trials are required to
      clearly identify the effectiveness of PRF regarding this subject.

PMID- 30277952
TI  - Achondroplasia: Orocraniofacial Features and Orthodontic-Surgical Management
      Guidelines Proposal.
AB  - In this study, the authors aimed to describe orocraniofacial features and to
      suggest orthodontic-surgical managements in achondroplasia, based on a literature
      review. The authors focused on skeletal and dentoalveolar malocclusion in order
      to highlight the place of orthognathic surgery, based on our experience of 3
      patients. Maxillary hypoplasia in achondroplasia typically results in an Angle
      class III malocclusion with an anterior open bite. The other orocraniofacial
      features include enlarged calvarium, prominent forehead and frontal bossing,
      midface hypoplasia, elongated lower face and saddle-shaped nose due to lack of
      development of the nasomaxillary complex.All our patients had a typical facial
      appearance but each of them had their own particularities regarding medical
      history and severity of the dentoskeletal dysmorphosis. Two of them were
      successfully treated by orthognathic surgery; the other declined surgical
      treatment and underwent orthopedic treatment only (anchorage plates). The
      treatment failure of this 3rd patient raises the question of the efficiency of
      anchorage plates in achondroplasia. In the light of the literature and our
      results, the authors conclude the need for personalized management based on age,
      medical history, severity of the dentoskeletal dysmorphosis, functional and/or
      esthetic disorders, and the patient's needs and requests. In any patient,
      orthodontic management should be initiated at an early age, and orthognathic
      surgery modalities should be personalized and adapted to each situation.

PMID- 30277953
TI  - Huge Extra Cranial Arteriovenous Malformation Presenting as Fluctuant Mass in
      Scalp.
AB  - Arteriovenous malformation (AVM) of the scalp is an uncommon condition. Clinical
      manifestations usually include local pain, pulsatile mass, headache, numbness,
      tinnitus; and less frequently, necrosis and hemorrhage. This study discusses and
      illustrates an unusual case of AVM in scalp with its radiologic appearance and
      clinical features.

PMID- 30277954
TI  - Jug Handle Tributary of Internal Jugular Vein: A Potentially Dangerous Venous
      Variation.
AB  - Variations of internal jugular vein (IJV) are rare and are surgically important.
      Here an unreported variation of IJV is presented. Right IJV had an unusual vein
      joining it in the form of a "jug handle." This vein arose from the junction of
      IJV and common facial vein (CFV), coursed down for 3 cm and joined IJV again. The
      CFV was dilated. Knowledge of this rare case could be useful to craniofacial
      surgeons, radiologists, and anesthesiologists. It might decrease the chances of
      iatrogenic bleeding during head and neck surgeries and radiologic procedures.

PMID- 30277955
TI  - Intra- and Postoperative Complications of Le Fort I Maxillary Osteotomy.
AB  - BACKGROUND: The Le Fort I maxillary osteotomy is a versatile and simple
      procedure, which has gained popularity nowadays, to correct a wide range of
      malocclusion and maxillofacial deformities. This procedure is often associated
      with significant but rare postoperative complications. The aim of this study was
      to evaluate the types and frequencies of intra- and perioperative complications
      related to Le Fort I osteotomies in noncleft Iranian patients. MATERIALS AND
      METHODS: In this prospective study, all the healthy systemic patients, (ASA I,
      II) with the age range of 18 to 30 years from both genders, who had the skeletal
      class II or III deformities and required only isolated 1-piece maxillary Le Fort
      I osteotomy, were included in this study. These patients had no craniofacial
      cleft history and were candidates for orthognathic surgery in Maxillofacial
      Surgery Department of Qaem Hospital of Mashhad (Iran), 2015 to 2017. All of the
      operations were carried out or supervised by a single surgeon and
      anesthesiologist using the same protocol. The patients were monitored for
      occurrence of intra- or postoperative complications till 6 months. The t-test,
      Chi-squared test, and Fisher exact test were performed for data analysis using
      SPSS version 16 (SPSS Inc, Chicago, IL). RESULTS: In the present study, a total
      of 114 consecutive patients with the average age of 22 +/- 5 years from October
      2015 to November 2017 were recruited. About 77 (67.54%) patients were presented
      skeletal class III deformity and 37 (32.46%) were class II. The most prevalent
      maxillary movement after Le Fort I osteotomy was identified to be isolated
      maxillary advancement in 51 (44.75%) patients. Only 10 (8.77%) of all 114
      patients confronted surgical complications. Hemorrhagic complication (arterial
      bleeding from descending palatine artery and epistaxis) and anatomic
      complications (septal deviation and bad fracture) would be the most prevalent
      complications with the frequency of 5.25% and 3.5% in total. Maxillary setback
      with impaction presented the highest rate (36.4%) of complications compared to
      other maxillary movement types. On balance, there was a significant association
      between Le Fort I surgery complications and maxillary movement types in our
      research (P = 0.002). CONCLUSION: The rate of intra- and postoperative
      complications following Le Fort I osteotomy for healthy noncleft adults in our
      center was low. Therefore, it can be concluded that this technique is safe and
      reliable. The maxillofacial surgeon should pay more attention for prevention or
      even management of the risk of intra- and perioperative complications in patients
      with anatomic irregularities (previous craniofacial cleft or trauma history) and
      those who required maxillary setback concomitant with impaction movements.

PMID- 30277956
TI  - Three Dimensional Printed Bone Implants in the Clinic.
AB  - Implants are being continuously developed to achieve personalized therapy. With
      the advent of 3-dimensional (3D) printing, it is becoming possible to produce
      customized precisely fitting implants that can be derived from 3D images fed into
      3D printers. In addition, it is possible to combine various materials, such as
      ceramics, to render these constructs osteoconductive or growth factors to make
      them osteoinductive. Constructs can be seeded with cells to engineer bone tissue.
      Alternatively, it is possible to load cells into the biomaterial to form so
      called bioink and print them together to from 3D bioprinted constructs that are
      characterized by having more homogenous cell distribution in their matrix. To
      date, 3D printing was applied in the clinic mostly for surgical training and for
      planning of surgery, with limited use in producing 3D implants for clinical
      application. Few examples exist so far, which include mostly the 3D printed
      implants applied in maxillofacial surgery and in orthopedic surgery, which are
      discussed in this report. Wider clinical application of 3D printing will help the
      adoption of 3D printers as essential tools in the clinics in future and thus,
      contribute to realization of personalized medicine.

PMID- 30277957
TI  - Strategically Integrating Instructional Designers in Medical Education.

PMID- 30277958
TI  - Educating for Indigenous Health Equity: An International Consensus Statement.
AB  - The determinants of health inequities between Indigenous and non-Indigenous
      populations include factors amenable to medical education's influence, for
      example, the competence of the medical workforce to provide effective and
      equitable care to Indigenous populations. Medical education institutions have an
      important role to play in eliminating these inequities. However, there is
      evidence that medical education is not adequately fulfilling this role, and in
      fact may be complicit in perpetuating inequities.This article seeks to examine
      the factors underpinning medical education's role in Indigenous health inequity,
      in order to inform interventions to address these factors. The authors developed
      a consensus statement that synthesizes evidence from research, evaluation, and
      the collective experience of an international research collaboration including
      experts in Indigenous medical education. The statement describes foundational
      processes that limit Indigenous health development in medical education and
      articulates key principles that can be applied at multiple levels to advance
      Indigenous health equity.The authors recognize colonization, racism, and
      privilege as fundamental determinants of Indigenous health that are also deeply
      embedded in Western medical education. In order to contribute effectively to
      Indigenous health development, medical education institutions must engage in
      decolonization processes and address racism and privilege at curricular and
      institutional levels. Indigenous health curricula must be formalized and
      comprehensive, and must be consistently reinforced in all educational
      environments. Institutions' responsibilities extend to advocacy for health system
      and broader societal reform to reduce and eliminate health inequities. These
      activities must be adequately resourced and underpinned by investment in
      infrastructure and Indigenous leadership.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- 30277959
TI  - Sentinel Emotional Events: The Nature, Triggers, and Effects of Shame Experiences
      in Medical Residents.
AB  - PURPOSE: This study explores an under-investigated topic, how medical residents
      experience shame within clinical learning environments, by asking residents to
      reflect on (1) the nature of their shame experiences; (2) the events that
      triggered, and factors that contributed to, those shame experiences; and (3) the
      perceived effects of those shame experiences. METHOD: In this hermeneutic
      phenomenology study, the authors recruited 12 (self-nominated) residents from an
      internal medicine residency at a large teaching hospital in the United States.
      Data collection from each participant included (1) a written reflection about an
      experience during medical training in which the participant felt 'flawed,
      deficient, or unworthy,' and (2) a semi-structured interview that explored the
      participant's shame experience(s) in depth. The data were analyzed according to
      the hermeneutic traditions, producing rich descriptions about participants' shame
      experiences. RESULTS: Participants' shame experiences ranged from debilitating
      emotional and physical reactions to more insidious, fleeting reactions.
      Participants reported shame triggers relating to patient care, learning
      processes, and personal goals; numerous factors contributed to their shame
      experiences. The effects of shame reactions included social isolation,
      disengagement from learning, impaired wellness, unprofessional behavior, and
      impaired empathy. Positive effects of shame reactions included enhanced learning,
      increased willingness to reach out for help, and improved relationships.
      CONCLUSIONS: Shame reactions can be sentinel emotional events with significant
      physical and/or psychological effects in medical learners. This study has
      implications for learners, educators, and patients, and it may pave the way
      toward open, honest conversations about the role shame plays in medical
      education.Written work prepared by employees of the Federal Government as part of
      their official duties is, under the U.S. Copyright Act, a "work of the United
      States Government" for which copyright protection under Title 17 of the United
      States Code is not available. As such, copyright does not extend to the
      contributions of employees of the Federal Government.

PMID- 30277960
TI  - Affirmative Action and Holistic Review in Medical School Admissions: Where We
      Have Been And Where We Are Going.
AB  - Current challenges to affirmative action policies are cause for concern for
      medical schools that employ holistic admissions processes, which consider an
      applicant's race, ethnicity, gender, status as a first-generation college
      student, educational and socioeconomic status, geographical location, past
      experiences with minority and underserved populations, social capital, and
      immigration status. Students from minority and underserved communities bring with
      them experiences and perspectives that may enhance the care they provide to
      underserved patients, improving patient outcomes. Student body diversity is also
      associated with increases in students' academic performance, retention, community
      engagement, cooperation, and openness to different ideas and perspectives, and
      institutions that foster diversity tend to be nurturing places where all students
      and faculty can thrive.The use of race as a factor in admissions has been upheld
      in three Supreme Court decisions. Yet, the Supreme Court likely will rule again
      on this issue. In the meantime, medical schools must maintain or increase support
      for science, technology, engineering, and math academic enrichment programs at
      all levels, stay informed about their institutional climate, and support a
      holistic admissions process that considers race and socioeconomic status. Doing
      so will help disadvantaged students overcome the intergenerational barriers
      created by race, ethnicity, and poverty and help grow a culturally-competent
      health care workforce, which is essential to improving individual and population
      health and narrowing racial and ethnic health disparities.

PMID- 30277961
TI  - New CPG for Torticollis!

PMID- 30277962
TI  - Physical Therapy Management of Congenital Muscular Torticollis: A 2018 Evidence
      Based Clinical Practice Guideline From the APTA Academy of Pediatric Physical
      Therapy.
AB  - BACKGROUND: Congenital muscular torticollis (CMT) is a postural deformity evident
      shortly after birth, typically characterized by lateral flexion/side bending of
      the head to one side and cervical rotation/head turning to the opposite side due
      to unilateral shortening of the sternocleidomastoid muscle; it may be accompanied
      by other neurological or musculoskeletal conditions. Infants with CMT should be
      referred to physical therapists to treat these postural asymmetries as soon as
      they are identified. PURPOSE: This update of the 2013 CMT clinical practice
      guideline (CPG) informs clinicians and families as to whom to monitor, treat,
      and/or refer and when and what to treat. It links 17 action statements with
      explicit levels of critically appraised evidence and expert opinion with
      recommendations on implementation of the CMT CPG into practice.
      RESULTS/CONCLUSIONS: The CPG addresses the following: education for prevention;
      referral; screening; examination and evaluation; prognosis; first-choice and
      supplemental interventions; consultation; discontinuation from direct
      intervention; reassessment and discharge; implementation and compliance audits;
      and research recommendations. Flow sheets for referral paths and classification
      of CMT severity have been updated.

PMID- 30277963
TI  - Commentary on "Transcranial Direct-Current Stimulation on Motor Function in
      Pediatric Cerebral Palsy: A Systematic Review".

PMID- 30277964
TI  - Commentary on "Effects of a Gaming Platform on Balance Training for Children With
      Cerebral Palsy".

PMID- 30277965
TI  - Commentary on "Physical Therapist Coaching to Improve Physical Activity in
      Children With Brain Tumors: A Pilot Study".

PMID- 30277966
TI  - Physical Therapists' Use and Alteration of Standardized Assessments of Motor
      Function in Children.
AB  - PURPOSE: This study presents survey responses of pediatric physical therapists'
      use and alteration of standardized assessments of motor function in children aged
      2 to 10 years. METHODS: Electronic and paper surveys were distributed to
      practicing physical therapists through the APTA Academy of Pediatric Physical
      Therapy electronic newsletter and 2 national conferences. Data were analyzed by
      response frequencies, qualitative responses, and chi(2) analyses for demographic
      characteristics. RESULTS: A total of 497 pediatric physical therapists responded.
      Most (93%) reported using standardized assessments, with the majority (84%)
      reporting the normative scores. Almost all respondents (94%) also reported that
      they at least occasionally modify assessments. CONCLUSION: Standardized
      assessments are used by most therapists, but the high use of modifications during
      testing is concerning. Survey reports from therapists indicate a disconnect
      between standardized assessments and the needs of the child, leaving clinicians
      working to report required scores while maintaining validity of testing
      procedures.

PMID- 30277967
TI  - Commentary on "Physical Therapists' Use and Alteration of Standardized
      Assessments of Motor Function in Children".

PMID- 30277968
TI  - Commentary on "Adapted Motivational Interviewing to Promote Exercise in
      Adolescents With Congenital Heart Disease: A Pilot Trial".

PMID- 30277969
TI  - Stepping Activity in Children With Congenital Myotonic Dystrophy.
AB  - PURPOSE: The purpose of this study was to investigate the physical activity
      levels in children with congenital myotonic dystrophy (CDM), and to examine
      whether patient clinical and functional characteristics correlated to physical
      activity. METHODS: Twenty-five children with CDM were assessed on functional
      measures, clinical measures, and physical activity levels. RESULTS: Results
      support that children with CDM spend the majority of their time inactive. There
      was a negative correlation between inactivity and cytosine-thymine-guanine
      repeats, suggesting increased inactivity with increased CDM severity. Age, body
      mass index, and lean muscle mass may be factors influencing activity levels.
      CONCLUSIONS: Children in this study received one-third the recommended steps per
      day. The number of steps per day is not correlated with clinical measures.

PMID- 30277970
TI  - Commentary on "Stepping Activity in Children With Congenital Myotonic Dystrophy".

PMID- 30277971
TI  - Whole-Body Vibration Training Designed to Improve Functional Impairments After
      Pediatric Inpatient Anticancer Therapy: A Pilot Study.
AB  - PURPOSE: To assess a whole-body vibration (WBV) intervention for children after
      cancer treatment. METHODS: Eleven children after inpatient anticancer therapy
      participated in a 12-week supervised WBV intervention, which consisted of one 9-
      to 13-minute WBV session per week, with 5 to 9 minutes' overall vibration time.
      Feasibility was defined as the ability to participate in WBV training without
      reporting adverse events. The number of offered and completed training sessions,
      program acceptance, and measures of function were assessed. RESULTS: Nine
      participants completed the WBV intervention without any WBV-related adverse
      events. The adherence rate was 87.96%. Only minor side effects were reported and
      there was general program acceptance. We found indications that WBV has positive
      effects on knee extensor strength and active ankle dorsiflexion range of motion.
      CONCLUSIONS: WBV was feasible, safe, and well received among children after
      inpatient anticancer therapy. No health deteriorations were observed. Positive
      effects need to be confirmed in future trials.

PMID- 30277972
TI  - Commentary on "Whole-Body Vibration Training Designed to Improve Functional
      Impairments After Pediatric Inpatient Anticancer Therapy: A Pilot Study".

PMID- 30277973
TI  - Walking and Fitness Improvements in a Child With Diplegic Cerebral Palsy
      Following Motor-Assisted Elliptical Intervention.
AB  - PURPOSE: To quantify effects of motor-assisted elliptical (Intelligently
      Controlled Assistive Rehabilitation Elliptical [ICARE]) training on walking and
      fitness of a child with cerebral palsy (CP). KEY POINTS: A 12-year-old boy with
      walking limitations due to spastic diplegic CP (Gross Motor Function
      Classification System II) participated in 24 sessions of primarily moderate- to
      vigorous-intensity ICARE exercise. Fitness improvements were evidenced clinically
      across sessions by the child's capacity to train for longer periods, at faster
      speeds, and while overriding motor's assistance. Postintervention, the child
      walked faster with greater stability and endurance and more rapidly completed the
      modified Time Up and Go test. CONCLUSION: The child's fitness and gait improved
      following engagement in a moderate- to vigorous-intensity gait-like exercise
      intervention. RECOMMENDATIONS FOR CLINICAL PRACTICE: Integration of moderate- to
      vigorous-intensity motor-assisted elliptical training can promote simultaneous
      gains in fitness and function for children with CP.

PMID- 30277975
TI  - In response.

PMID- 30277976
TI  - Significance of Lateral Process Fractures Associated With Talar Neck and Body
      Fractures.
AB  - OBJECTIVES: To determine whether fracture of the lateral process (LP) elevates
      the risk of development of radiographic subtalar arthrosis in patients with talar
      body and neck fractures. DESIGN: Retrospective review. SETTING: Level 1 academic
      trauma center. PATIENTS/PARTICIPANTS: Eighty-two patients with 43 talar neck and
      43 talar body fractures treated over a 5-year period. INTERVENTION: Preoperative
      and postoperative radiographs were evaluated for fracture of the LP of the talus
      and subsequent development of radiographic subtalar arthritis. MAIN OUTCOME
      MEASUREMENTS: Radiographic evidence of subtalar arthritis. RESULTS: Seventy-six
      percent of talar neck fractures with involvement of the LP went on to develop
      radiographic evidence of subtalar arthrosis compared with 36% of talar neck
      fractures without LP involvement (P = 0.035). Thirty of the fractures involving
      the LP had a separate LP fragment. Fifteen of the 30 fractures with a separate LP
      fragment that underwent reduction and fixation developed radiographic evidence of
      subtalar arthrosis, whereas all 13 fractures with an independent LP fragment that
      did not have fixation of the LP went on to develop radiographic evidence of
      subtalar arthritis (P = 0.001). Comminution of the inferior talar articular
      surface was found to significantly increase the risk of radiographic subtalar
      arthritis in both talar body and talar neck fractures (P = 0.0003). An anatomic
      reduction of both talar neck and body fractures was found to be associated with a
      lower incidence of radiographic subtalar arthritis (P = 0.00001). CONCLUSION:
      Comminution of the inferior articular surface of the talus elevates the risk of
      subtalar arthritis in patients with both talar neck and body fractures. Fracture
      of the LP is a marker for injury to the talar inferior articular surface and
      increases the risk for the radiographic finding of subtalar arthritis in patients
      with talar neck fractures. LEVEL OF EVIDENCE: Prognostic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30277977
TI  - Risk Factors for Conversion to Total Hip Arthroplasty After Acetabular Fractures
      Involving the Posterior Wall.
AB  - OBJECTIVES: Identify risk factors for early conversion to total hip arthroplasty
      (THA) in an effort to aid in counseling patients and selecting the optimal
      treatment for patients who sustain a fracture involving the posterior wall of the
      acetabulum. DESIGN: Retrospective cohort analysis. SETTING: Level I trauma
      center. PATIENTS: Patients with acetabular fractures involving the posterior wall
      managed with open reduction internal fixation at least 4 years out from surgery.
      INTERVENTION: Preoperative and postoperative computed tomography scans were
      reviewed for injury characteristics and reduction quality. Participants were
      contacted by telephone to document reoperations and functional outcomes including
      the SF-8 and modified Merle d'Aubigne Hip Scale. MAIN OUTCOME MEASURE: Conversion
      to THA. RESULTS: The overall rate of conversion to THA was 5% at 2 years, 14% at
      5 years, and 17% at 9 years. Presence of 5 specific radiographic features was
      associated with a 50% rate of conversion to THA in contrast to 11% if 4 or less
      features were present. Among cases with less than 1 mm of diastasis/step-off on
      postoperative computed tomography scan, there were no THA conversions, 10%
      conversion for 1-4 mm, and 54% if 4 mm or more of malreduction. There was no
      difference in SF-8 or modified Merle d'Aubigne scores comparing patients who
      underwent THA and those who did not. CONCLUSIONS: Acetabular fractures with
      posterior wall involvement are associated with a significantly higher rate of
      conversion to THA if reduction is not near-anatomic. A combination of
      clinical/radiographic findings is associated with poorer reductions and higher
      rate of conversion to THA. LEVEL OF EVIDENCE: Prognostic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30277978
TI  - Clinical Outcomes and Complications of the Surgical Implant Generation Network
      (SIGN) Intramedullary Nail: A Systematic Review and Meta-analysis.
AB  - OBJECTIVES: This study is a systematic review and meta-analysis of the clinical
      outcomes and pooled complication rate of femoral, tibial, and humeral fracture
      fixation using SIGN nails. We aimed to compare the pooled rate of adverse events
      based on the country of study origin, acute versus delayed fracture fixation, and
      length of follow up. METHODS: We searched PubMed/MEDLINE/Cochrane databases from
      2000-2016 for English language studies. There was substantial heterogeneity among
      included studies. Therefore, we employed sub-group analysis of varying adverse
      events and removal of potential outlier studies based on the 'remove one'
      sensitivity analysis, to address the heterogeneity across studies. A funnel plot
      was drawn and inspected visually to assess publication bias. We reported pooled
      complication rates for each adverse event with 95% prediction interval (PI).
      RESULTS: There were 14 studies with 47,169 cases across 58 different LMICs. The
      average age was 33 +/- 14 years, with 83% male and 17% female. Sixty percent of
      SIGN nails utilized in these 14 studies were used in femur fracture fixation, 38%
      in tibial shaft fractures, and the remaining 2% for humeral shaft fractures.
      Approximately 23% of patients had follow-up data recorded. All studies that
      measured clinical outcome indicated that >90% achieved full weight-bearing
      status, favorable range of motion (knee range of motion >90 degrees according to
      the SIGN database), and radiographic or clinical union depending on the specific
      variable(s) measured in each study. The overall complication rate was 5.2% (4.4% 
      6.4%). Malalignment (>5 degrees angulation in any plane) was the most common
      complication (7.6%), followed by delayed/non-union (6.9%), infection (5.9%), and
      hardware failure, (3.2%). CONCLUSION: Overall, the use of SIGN nails in fixing
      femoral, tibial, and humeral shaft fractures demonstrates good results with a
      high rate of return to full weight-bearing and radiographic/clinical union. The
      most common complications when using the SIGN nail are malalignment, delayed/non
      union, infection and hardware failure. LEVEL OF EVIDENCE: Level-IV meta-analysis.

PMID- 30277979
TI  - Impact of Direct Oral Anticoagulants (DOACs) in Patients with Hip Fractures.
AB  - OBJECTIVE: To assess the impact of direct oral anticoagulant (DOAC) intake
      compared to Coumadin (COU) in patients suffering hip fractures (HF). DESIGN:
      Retrospective cohort analysis SETTING:: Level 1 Trauma Center INTERVENTION::
      Timing of surgical hip fixation. PATIENTS: Three-hundred twenty patients >= 65
      years of age with isolated HF were enrolled into the study: 207 (64.7%) without
      any antithrombotic therapy (no-ATT), 59 (18.4%) on COU and 54 (16.9%) on DOACs.
      MAIN OUTCOME MEASUREMENTS: Time to surgery, blood loss, mortality, hospital
      length of stay, red blood cell transfusion, use of reversal agents and Charlson
      Comorbidity Index. RESULTS: Patients on COU and DOACs had a higher Charlson
      Comorbidity Index compared to the no-ATT group (p < 0.0001). Despite the fact
      that significantly more patients received reversal agents in the COU group
      compared to DOAC medication (p<0.0001), percentage of transfused patients were
      similar (54.2% vs. 53.7%). Time to surgery was significantly shorter in the no
      ATT group when compared with DOAC patients (12 to 29.5 hours respectively). No
      difference in postoperative hemorrhage, ICU length of stay and mortality was
      observed between groups. CONCLUSIONS: DOAC medication in HF patients caused long
      elapse time until surgical repair. We found no evidence of higher bleeding rates
      in HF patients on DOACs compared to COUs. Earlier HF fixation might be indicated
      in DOAC patients. LEVEL OF EVIDENCE: Retrospective Cohort study, level III.

PMID- 30277980
TI  - Foot Function After Surgically Treated Intraarticular Calcaneal Fractures:
      Correlation of Clinical and Pedobarographic Results of 65 Patients Followed for 8
      Years.
AB  - OBJECTIVES: To correlate functional deficits after surgical treatment of
      displaced intraarticular calcaneal fractures (DIACFs) as measured through dynamic
      pedobarography with clinical and radiographic long-term results. DESIGN:
      Retrospective single-center study. SETTING: Level 1 trauma center. PATIENTS:
      Sixty-five patients with unilateral DIACFs, reexamined at an average of 8.1 years
      after surgery. INTERVENTION: Internal fixation of DIACF with lateral plate or
      percutaneous screws. MAIN OUTCOME MEASUREMENTS: Dynamic pedobarography, AOFAS,
      Zwipp, SF-36 scores, Foot Function Index, Bohler angle, and articular congruity.
      RESULTS: When compared with the uninjured side, pedobarography of the operated
      foot revealed a significantly increased contact area of the hindfoot and midfoot,
      with a decreased contact area under first/second metatarsal (MT) and first/second
      toe after DIACF. Maximum pressure and pressure time integral were significantly
      increased at the midfoot and lateral MT with a decrease under the hindfoot and
      first to second MT/toe. Midfoot pressure time integral correlated with the range
      of plantarflexion. Fracture classification correlated with MT 1 contact time.
      Hindfoot and MT contact times were negatively correlated with Bohler angle.
      Patients with the smallest side-to-side differences in pedobarogaphy had overall
      highest scores and significantly greater ankle/hindfoot range of motion at follow
      up. CONCLUSIONS: Significant correlations were found between clinical and
      pedobarographic results. Increased contact areas and time at the midfoot
      indicating a lateral load shift correlated with inferior outcome and decreased
      subtalar motion. These results support the importance of reconstruction of the
      subtalar joint and overall bony morphology of the calcaneus with preservation of
      subtalar motion as necessary for global foot function. LEVEL OF EVIDENCE:
      Therapeutic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 30277981
TI  - Decreased Lean Psoas Cross-sectional Area is Associated with Increased One-year
      All-cause Mortality in Male Elderly Orthopaedic Trauma Patients.
AB  - OBJECTIVES: To investigate the association between lean psoas Cross-sectional
      Area (CSA) and one-year all-cause mortality in elderly patients sustaining pelvic
      and long bone fractures. DESIGN: Retrospective cohort SETTING:: Level one center
      PATIENTS:: Elderly trauma patients admitted from 2007-2014. METHODS: We reviewed
      demographic and clinical data, injury mechanism, fracture OTA/AO classification,
      and mortality. Axial Computed Tomography (CT) images were used to measure lean
      psoas CSA at the L3-L4 disk space. Cox proportional hazard regression analysis
      was used to estimate one-year mortality association with psoas CSA in crude and
      adjusted for age, BMI, ISS, medical comorbidities and discharge destination in
      total population and stratified by gender. MAIN OUTCOME MEASUREMENT: One-year all
      cause mortality defined as death within 12 months from date of hospitalization.
      RESULTS: 558 patients (54% female, 46% male) were analyzed. The pelvis was most
      commonly fractured (37.81%). A statistically significant association was observed
      between decreased lean psoas CSA and one-year mortality in total population
      [Hazard Ratio (HR)= 0.93 (95% Confidence Interval (CI)= 0.90-0.96), p<0.0001].
      Stratification by gender revealed a statistically significant mortality HR in
      male patients [HR= 0.89 (95% CI= 0.84-0.96), p= 0.002]. We did not find a
      statistically significant mortality HR in female patients [HR= 0.95 (95% CI= 0.89
      1.01), p= 0.103]. CONCLUSIONS: In this cohort of elderly orthopaedic trauma
      patients, decreased lean psoas CSA was associated with increased one-year all
      cause mortality in total population and males. Further investigation of the
      association of sarcopenia with mortality in the elderly is warranted. LEVEL OF
      EVIDENCE: Level III prognostic.

PMID- 30277982
TI  - Nail Plate Combination (NPC) Technique for Native and Periprosthetic Distal Femur
      Fractures: A Technical Trick.
AB  - SUMMARY: In the elderly, low energy distal femur fractures (native or
      periprosthetic) can be devastating injuries, carrying high rates of morbidity and
      mortality, comparable to the hip fracture population. Poor, osteoporotic bone
      quality facilitates fracture in a vulnerable anatomic region and as a result,
      operative fixation can be challenging. With goals of early mobilization to reduce
      subsequent complication risk, employing the nail plate combination (NPC)
      technique can offer stable, balanced fixation allowing for immediate weight
      bearing and early mobilization. We outline the rationale, technical steps, and
      early clinical outcomes following NPC in the treatment of osteoporotic distal
      femur (native or periprosthetic) fractures.

PMID- 30277983
TI  - Self-Reported Recovery Likelihood Predicts Higher Physician Ratings following
      Orthopaedic Surgery.
AB  - OBJECTIVES: What are the differences between elective and trauma patient
      satisfaction and do patient and diagnosis factors predict physician scores?
      DESIGN: Prospective cohort study SETTING:: Urban Level 1 Trauma center
      PATIENTS/PARTICIPANTS:: 323 trauma patients and 433 elective orthopaedic patients
      treated at our center by the same surgeons INTERVENTION:: Trauma patients treated
      surgery for one or more fractures; elective patients treated with hip, knee, or
      shoulder arthroplasty, or rotator cuff repair. MAIN OUTCOME MEASUREMENTS:
      Telephone survey regarding patient experience and satisfaction with their care.
      The survey included questions from Hospital Consumer Assessment of Healthcare
      Providers and Systems surveys (HCAHPS), and responses were rated on a 1-5 point
      Likert scale (5 best). RESULTS: Elective surgery patients had mean age of 56.4
      years, and trauma patients were mean 50.3 years of age. Trauma patients rated
      their likelihood to make a full recovery lower than elective patients, (Median,
      Interquartile Range), 5.0(1.0) vs. 4.0(2.0) (p<0.001). Following multivariate
      binary logistic regression, patients who rated the hospital higher (>=4 versus
      <=3), were more likely OR=10.0, 95% CI [6.4, 15.8] to score physicians better.
      Similarly, patients who scored their overall likelihood of recovering >=4
      compared to <=3, were more likely OR=3.6, 95% CI [2.9, 5.6] to rate their
      physicians more positively. CONCLUSIONS: Patient perceptions including their
      likelihood to make a full recovery and their overall impression of the hospital
      predicted higher physician scores. We conclude that these physician scores are
      subject to patient perception biases and are not independent of the overall care
      experience. We recommend HCAHPS and physician ratings websites include internal
      controls, such as the patient perception of overall likelihood to recover, to
      aide in interpreting survey results. LEVEL OF EVIDENCE: Level 2: Prospective
      comparative study.

PMID- 30277984
TI  - Intraoperative assessment of coronal alignment in distal femur fracture fixation:
      Technical Trick.
AB  - Supracondylar femur fractures represent a challenging and common injury treated
      by many orthopedic surgeons. An array of surgical fixation options has been
      developed to help the treating surgeon restore normal anatomic alignment of these
      fractures, and lateral precontoured condylar femoral locking plates have become a
      common implant for most surgeons in treating these fractures. Though these
      precontoured plates provide significant benefit to the treating physician in
      regards to gaining appropriate bony fixation, common technical errors that may
      lead to malalignment when utilizing these plates have been described. Avoiding
      these errors will help improve patient outcomes. Here, we describe a novel,
      inexpensive, and universally available technique that may aid the treating
      surgeon in restoring coronal alignment when treating distal femur fractures.

PMID- 30277985
TI  - Knee pain and functional scores after intramedullary nailing of tibial shaft
      fractures using a suprapatellar approach.
AB  - OBJECTIVES: To evaluate the effects of intramedullar nailing of the tibia using a
      suprapatellar approach with respect to pain and function of the knee. DESIGN:
      Prospective clinical investigation SETTING:: Academic level I trauma center
      PATIENTS/PARTICIPANTS:: Twenty-one patients with tibial shaft fractures (OTA 42A
      B-C) with a minimum of twelve months follow up. INTERVENTION: Locked
      intramedullary nailing using a suprapatellar approach MAIN OUTCOME MEASUREMENTS::
      Radiographic evaluation for nail position proximally, tibial shaft alignment and
      union, anterior knee pain using the Visual Analog Scale (VAS), and knee function
      evaluation using the Lysholm and SF-36 scores. Examination of intra-articular
      damage was performed using intraoperative patellofemoral arthroscopy before and
      after nail insertion. RESULTS: The mean age of the patients was 35.4+/-12.4 years
      (range, 18-63 years) and the mean follow-up period was 15.62+/-3.2 months (range,
      12-21 months). The VAS score for anterior knee pain was a mean of 1.0+/-1.3
      (range, 0-4). The SF-36 physical score was mean 45.1+/-9 and the SF-36 mental
      score was a mean of 51.7+/-9.9. The knee joint ROM was measured as 133.1 degrees
      +/-87 degrees  on the affected extremity side and 134.05 degrees +/-8.4 degrees 
      on the unaffected side. The mean Lysholm knee score was 95.76+/-4. No intra
      articular pathology was seen on arthroscopy after nail insertion. CONCLUSIONS:
      The suprapatellar approach for intramedullar nailing for tibial shaft fractures
      was not associated with either anterior knee pain or functional limitations of
      the knee in our series.

PMID- 30277986
TI  - Outcome Analysis of Surgical Stabilization of Rib Fractures in Trauma Patients.
AB  - OBJECTIVES: To compare outcomes in patients with rib fractures (RFX) who
      underwent surgical stabilization of rib fractures (SSRF) to those treated non
      operatively. DESIGN: Retrospective cohort study SETTING:: Two Level 1 Trauma
      Centers. Florida, USA PATIENTS:: 174 patients with multiple rib fractures divided
      in 2 groups: Patients with Surgically Stabilized Rib Fractures (n=87) were
      compared to non-operatively managed patients in the Matched Control Group (n=87).
      INTERVENTION: Surgical stabilization of rib fractures OUTCOME MEASUREMENTS:: Age,
      gender, ISS, RFX, mortality, hospital (HLOS) and ICU length of stay (ICULOS),
      days of mechanical ventilation (DMV), co-injuries, and time to surgery. Patients
      were further stratified by presence or absence of flail chest and pulmonary
      contusion. RESULTS: Flail chest, displaced RFX and pulmonary contusion were
      present significantly more often in SSRF patients compared to the MCG. Mortality
      was lower in SSRF group. HLOS and ICULOS were longer in SSRF group compared to
      the corresponding MCG patients regardless of timing to surgery (p<0.01 for all).
      SSRF patients with flail chest had comparable HLOS, ICULOS and DMV to MCG
      patients with flail chest (p>0.3 for all). SSRF patients without flail chest had
      significantly longer HLOS and ICULOS than MCG patients without flail chest
      (p<0.001 for both). Presence of pulmonary contusion did not affect lengths of
      stay. CONCLUSIONS: SSRF patients had reduced mortality compared to non
      operatively managed patients. HLOS, ICULOS and DMV were longer in SSRF patients
      than in MCG. When flail chest was present, lengths of stay were comparable.
      Pulmonary contusion did not appear to affect the surgical outcome. LEVEL OF
      EVIDENCE: Therapeutic Level III.

PMID- 30277988
TI  - Manipulation Under Anesthesia as a Treatment of Posttraumatic Elbow Stiffness:
      Should We Really?

PMID- 30277987
TI  - A Prospective Study of the Effectiveness of Paroxetine on the Onset of
      Posttraumatic Stress Disorder, Depression, and Health and Functional Outcomes
      After Trauma.
AB  - OBJECTIVES: To determine whether the administration of medication for
      posttraumatic stress disorder (PTSD) to injured trauma survivors prevents or
      mitigates PTSD. DESIGN: Double-blinded, placebo-controlled. SETTING: Level I
      trauma center. PATIENTS: One hundred and twenty patients admitted for traumatic
      orthopedic injury. INTERVENTION: Either paroxetine or placebo starting 2 weeks
      postinjury. MAIN OUTCOME MEASUREMENTS: PTSD symptoms were measured with the PTSD
      Checklist for DSM-IV. The Quick Inventory of Depressive Symptomatology (QIDS)
      assessed the presence and severity of DSM-IV-TR major depressive symptoms. The SF
      36 measured post-injury quality of life and social functioning. The Short
      Musculoskeletal Functional Assessment (SMFA) rated post-injury musculoskeletal
      function. RESULTS: The paroxetine group did not differ from the placebo group in
      proportions with PTSD as assessed at the 6-month or 12-month follow up or in
      proportions with major depression symptoms since the injury as assessed at the 3
      month follow up. The groups also did not differ at the 8-week follow up in amount
      of change from baseline in QIDS scores. The paroxetine group had a marginally
      greater increase from baseline in SF-36 functioning score at the 12-month follow
      up as compared with the placebo group and a marginally greater reduction from
      baseline in SMFA musculoskeletal functioning at the 12-month follow up as
      compared with the placebo group. CONCLUSIONS: These results suggest the potential
      for psychotropic medication to prevent or reduce posttraumatic stress symptoms
      and to improve the function and health of trauma patients. Further research is
      needed to confirm paroxetine's use for this purpose. LEVEL OF EVIDENCE:
      Therapeutic Level II.

PMID- 30277989
TI  - Knee Stiffness After Tibial Plateau Fractures: Predictors and Outcomes (OTA-41).
AB  - OBJECTIVES: What patient characteristics and injury factors predict decreased
      knee range of motion (ROM) after operative management of tibial plateau
      fractures? DESIGN: Prospective cohort study. SETTING: Academic medical center.
      PATIENTS: Over 11 years, tibial plateau fractures at a single academic
      institution were prospectively followed. A total of 266 patients were included in
      this study. INTERVENTION: Surgical repair of tibial plateau fractures and
      secondary interventions due to arthrofibrosis. MAIN OUTCOME MEASURE: Clinical
      outcomes were evaluated using the Short Musculoskeletal Function Assessment and
      ROM at 3-month, 6-month, and long-term follow-up. Secondary outcomes were
      considered as the need for a subsequent procedure due to arthrofibrosis. RESULTS:
      At 3-month follow-up, the mean ROM was 113 degrees. By long-term follow-up (mean
      = 17 months), the mean ROM improved to 125 degrees. Independent predictors of
      decreased knee ROM were the following: at 3-month follow-up, open fractures (P =
      0.047), application of a knee-spanning external fixator (P = 0.026), orthopaedic
      polytrauma (P = 0.003), and tibial spine involvement (P = 0.043); and at long
      term follow-up, nonwhite ethnicity (P = 0.003), increasing age (P = 0.003), and a
      deep infection (P = 0.002). Ten patients (3.7%) required a secondary procedure
      for arthrofibrosis. There was a significant improvement in the knee ROM (P <
      0.001) and functional outcomes (P = 0.004) following the intervention.
      CONCLUSIONS: At long-term follow-up, independent predictors of decreased knee ROM
      were nonwhite ethnicity, increasing age, and sustaining a postoperative
      complication of a deep infection. Secondary interventions were reliable
      treatments for arthrofibrosis. LEVEL OF EVIDENCE: Prognostic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30277990
TI  - The Incidence of Posterior Malleolar Involvement in Distal Spiral Tibia
      Fractures: Is it Higher than We Think?
AB  - OBJECTIVES: To investigate the incidence of concomitant posterior malleolar
      fractures (PMFs) in operative, distal-third, spiral tibia fractures. DESIGN:
      Prospective protocol with retrospective review of data. SETTING: Single, Level 1
      trauma center. PATIENTS/PARTICIPANTS: One hundred ninety-three consecutive,
      skeletally mature patients with operatively treated fractures of the distal
      third, tibial shaft and metaphysis. Pilon fractures were excluded. INTERVENTION:
      Computed tomography (CT) scans were obtained in all distal-third, spiral
      fractures of the tibia to determine fracture morphology and presence of a PMF.
      MAIN OUTCOME MEASUREMENTS: The incidence of concurrent PMFs in operative spiral
      fractures of the distal tibia. RESULTS: Twenty-six distal-third, spiral fractures
      were identified with an ipsilateral PMF diagnosed in 92.3% of cases (24 cases).
      PMFs were over 25 times more likely to occur in distal-third, spiral fractures
      when compared with other distal-third fracture patterns (relative risk = 25.7,
      95% confidence interval, 11.6-56.8). PMFs were treated with supplemental fixation
      in 23/24 (95.8%) cases. CONCLUSIONS: There is a high incidence of concomitant,
      ipsilateral fractures of the posterior malleolus in patients presenting with
      operative distal-third, spiral fractures of the tibia. A preoperative ankle
      computed tomography should be strongly considered in all cases with this specific
      fracture morphology. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 30277991
TI  - Reverse shoulder arthroplasty in acute fractures of the proximal humerus: Does
      tuberosity healing improve clinical outcomes?
AB  - OBJECTIVE: The study aimed to evaluate the clinical outcomes of reverse shoulder
      arthroplasty (RSA) in elderly patients with proximal humeral fractures and assess
      the role of tuberosity healing on the outcome. DESIGN: Case series SETTING::
      Multicentre clinical study of level-2 trauma centres PATIENTS/PARTICIPANTS:: We
      included 81 patients with a mean age of 78.5 +/- 6.5 years (range, 58.5-90.9
      years) and a non-reconstructable proximal humeral fracture. INTERVENTION: Modular
      reverse fracture shoulder arthroplasty. MAIN OUTCOME MEASUREMENTS: We determined
      range of motion, Constant score (CS), and the American Shoulder and Elbow
      Surgeons (ASES) Shoulder Score as clinical outcomes and evaluated tuberosity
      healing at six weeks, six months, one year, and two years. RESULTS: Tuberosities
      healed in most patients; 37 patients had completely healed tuberosities and 33
      patients had partially healed tuberosities, while 11 patients had unhealed
      tuberosities. However, no significant differences were found in the functional
      outcomes among the three groups (p > 0.05). CONCLUSIONS: Our results with a
      modular reverse prosthesis confirmed similar CSs, ASES Shoulder Scores, and
      tuberosity healing rates as reported in the current clinical evidence for RSA. We
      could not confirm that tuberosity healing improved functional outcomes; however,
      it should be noted that tuberosity healing was assessed using standard
      radiographs. Nevertheless, our study strengthens the consensus that RSA can be
      recommended for well-selected elderly patients with complex displaced proximal
      humeral fractures. LEVEL OF EVIDENCE: Therapeutic, level IV.

PMID- 30277992
TI  - Opioid Consumption After Knee Arthroscopy.
AB  - BACKGROUND: The opioid epidemic in the United States has placed increased
      pressure on physicians to engage in responsible opioid prescribing practices.
      However, surgeons currently have little information to guide their postoperative
      prescription decision-making. The purpose of this study was to assess opioid
      consumption after knee arthroscopy and identify preoperative factors that may
      predict higher opioid usage. METHODS: A prospective observational study of 221
      patients was conducted in patients undergoing outpatient knee arthroscopy for
      meniscal repair, partial meniscectomy, debridement, chondroplasty, or loose body
      removal. Participants recorded their daily opioid consumption in a postoperative
      pain diary. Total opioid consumption was calculated from counts of remaining
      pills at the 2-week and 6-week postoperative office visits. Variables, including
      age, sex, body mass index, smoking status, alcohol consumption, preoperative pain
      severity and duration, preoperative opioid usage, Patient-Reported Outcomes
      Measurement Information System (PROMIS) scores, and the Connor-Davidson
      Resilience Scale, were evaluated for an association with opioid consumption.
      RESULTS: Total opioid consumption ranged from 0 to 188 pills, with a median of 7
      pills (hydrocodone 5-mg equivalents). Forty-six percent of patients took <=5
      pills, 59% took <=10 pills, and 81% took <=20 pills. Fifty-six percent of
      patients had discontinued opioid usage by the third postoperative day. Eighty
      eight percent of patients had surplus opioid medication at the time of the final
      follow-up. Patients undergoing meniscal repair, smokers, and those taking
      preoperative opioids were significantly more likely to take >=20 pills (p <
      0.05). CONCLUSIONS: The median number of pills taken after knee arthroscopy is 7,
      with the majority of patients consuming <=20 pills. Meniscal repair, smoking, and
      preoperative opioid usage were associated with higher postoperative opioid
      consumption. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 30277993
TI  - Physical Activities That Cause High Friction Moments at the Cup in Hip Implants.
AB  - BACKGROUND: High friction moments in hip implants contribute to the aseptic
      loosening of cementless cups, of which there are approximately 100,000 cases per
      year; sustained joint loading may cause such high moments. The most "critical"
      physical activities associated with sustained joint loading were identified in
      this study. METHODS: Friction moments in the cup were telemetrically measured
      about 33,000 times in the endoprostheses of 9 subjects during >1,400 different
      activities. The highest moments were compared with the cup's fixation stability
      limit of approximately 4 Nm. RESULTS: A total of 124 different activities caused
      friction moments meeting or exceeding the critical limit, with the highest value
      of 11.5 Nm. Most involved sustained high contact forces before or during the
      activity. The highest peak moments (6.3 to 11.5 Nm) occurred when moving the
      contralateral leg during 1-legged stance, during breaststroke swimming, muscle
      stretching, 2-legged stance with muscle contraction, and during static 1-legged
      stance. The median moments were highest (3.4 to 3.9 Nm) for unstable 1-legged
      stance, whole-body vibration training, 2-legged stance with an unexpected push at
      the upper body, 1-legged stance while exercising the contralateral leg, and
      running after 2-legged stance. CONCLUSIONS: Frequent unloading plus simultaneous
      movement of the joint are required to maintain good joint lubrication and keep
      the friction moments low. Frequent, sustained high loads before or during an
      activity may cause or contribute to aseptic cup loosening. During the first
      months after hip arthroplasty, such activities should be avoided or reduced as
      much as possible. This especially applies during postoperative physiotherapy.
      Whether these guidelines also apply for subjects with knee implants or arthrotic
      hip or knee joints requires additional investigation. CLINICAL RELEVANCE: The
      risk of aseptic cup loosening may be reduced by avoiding sustained loading of hip
      implants without periodic joint movement.

PMID- 30277994
TI  - Continuous Near-Infrared Spectroscopy Demonstrates Limitations in Monitoring the
      Development of Acute Compartment Syndrome in Patients with Leg Injuries.
AB  - BACKGROUND: We recorded measurements of muscle perfusion using near-infrared
      spectroscopy (NIRS) and intramuscular pressure (IMP) in a study designed to
      develop a decision rule for predicting acute compartment syndrome (ACS). The
      purpose of this study was to report our experience measuring NIRS data in the
      context of this broader investigation and to explore factors related to
      variations in data capture. METHODS: One hundred and eighty-five patients with
      lower-leg injuries had data consisting of continuous NIRS measurement of the O2
      saturation in the anterior compartment of the injured limb and the contralateral
      (control) limb, and continuous IMP recording in the anterior and deep posterior
      compartments of the injured leg as part of their participation in an
      institutional review board-approved multicenter trial. All monitoring was done
      for a prescribed period of time. For both types of data, the percentage of valid
      data capture was defined as the ratio of the minutes of observed data points
      within a physiological range to the total minutes of expected data points.
      Clinically useful NIRS data required simultaneous data from the injured and
      control limbs to calculate the ratio. Statistical tests were used to compare the
      2 methods as well as factors associated with the percent of valid NIRS data
      capture. RESULTS: For the original cohort, clinically useful NIRS data were
      available a median of 9.1% of the expected time, while IMP data were captured a
      median of 87.6% of the expected time (p < 0.001). Excluding 46 patients who had
      erroneous NIRS data recorded, the median percentage was 31.6% for NIRS compared
      with 87.4% for IMP data (p < 0.00001). Fractures with an associated hematoma were
      less likely to have valid data points (odds ratio [OR], 0.53; p = 0.04). Gustilo
      types-I and II open fractures were more likely than Tscherne grades C0 and C1
      closed fractures to have valid data points (OR, 1.97; p = 0.03). CONCLUSIONS: In
      this study, NIRS data were not collected reliably. In contrast, IMP measurements
      were collected during >85% of the expected monitoring period. These data raise
      questions about the utility of current NIRS data capture technology for
      monitoring oxygenation in patients at risk of ACS.

PMID- 30277995
TI  - Cost-Effectiveness of Surgical and Nonsurgical Treatments for Unicompartmental
      Knee Arthritis: A Markov Model.
AB  - BACKGROUND: There has been increased utilization of surgical options for the
      treatment of end-stage unicompartmental arthritis in patients at both extremes of
      the age spectrum. The purpose of this study was to determine how these changing
      paradigms affected the lifetime cost-effectiveness of total knee arthroplasty
      (TKA), unicompartmental knee arthroplasty (UKA), and nonsurgical treatment (NST).
      METHODS: Using a Markov decision analytic model, we assessed how lifetime costs
      and quality-adjusted life years (QALYs) vary as a function of age at the time of
      initial treatment (ATIT) of patients with end-stage unicompartmental knee
      osteoarthritis undergoing TKA, UKA, and NST. Separate models were estimated for
      ATITs at 5-year intervals from 40 through 90 years. Direct medical costs, QALYs,
      and transition probabilities were determined from the published literature.
      Indirect costs (lost wages, Social Security disability collections, and value of
      missed workdays) were calculated. Cost-effectiveness and incremental cost
      effectiveness ratios (ICERs) were calculated for each treatment at each ATIT. The
      model assumed no crossover from NST to UKA or TKA. ICERs were compared with a
      willingness-to-pay threshold of 50,000 U.S. dollars, and a 1-way sensitivity
      analysis was used to assess the robustness of ICER-based treatment decisions.
      Societal savings were estimated. RESULTS: In the base-case model, surgical
      treatments were less expensive and provided a greater number of QALYs than NST
      from 40 to 69 years of age. From 70 years of age and onward, surgical treatments
      remained cost-effective compared with NST, with ICERs remaining below the
      societal willingness-to-pay threshold. When surgical treatments were compared,
      UKA dominated TKA for all ATITs. The preferential use of UKA in all U.S. patients
      with unicompartmental osteoarthritis would result in an estimated lifetime
      societal savings of 987 million to 1.5 billion U.S. dollars per annual wave of
      patients undergoing treatment. CONCLUSIONS: In this preliminary assessment,
      recent expansion of surgical treatments into younger and older age demographics
      appears to be cost-effective in the setting of unicompartmental knee
      osteoarthritis. Our findings suggest that NST should be used sparingly in
      patients below the age of 70 years and UKA should be chosen over TKA in order to
      maximize cost-effectiveness. LEVEL OF EVIDENCE: Economic and decision analysis
      Level IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 30277996
TI  - Retrieval Findings of Recalled Dual-Taper Hips.
AB  - BACKGROUND: The recent high-profile recalls of several dual-taper hip designs
      pose questions regarding why those designs perform poorly. We aimed to
      characterize taper damage in 1 recalled design to understand failure mechanisms
      to inform surgeons on which patients should be considered at risk of revision and
      when to revise. METHODS: High-precision measurement equipment was used to
      characterize the metal loss from the neck-stem interface of 116 retrieved
      Rejuvenate femoral stems (Stryker Howmedica Osteonics) revised because of an
      adverse reaction to metal debris. Head-neck taper surfaces were also
      investigated, and clinical and laboratory data were examined. RESULTS: The neck
      stem junction of each implant was moderately to severely corroded and showed a
      characteristic wear pattern on both male and female taper surfaces. The severity
      of taper damage was positively correlated with time to revision (coefficient,
      0.040 [95% confidence interval (CI), 0.028 to 0.051]; p < 0.0001) and with serum
      cobalt concentration (coefficient, 0.02 [95% CI, 0.01 to 0.02]; p < 0.0001) and
      serum chromium concentration (coefficient, 0.04 [95% CI, 0.009 to 0.070]; p =
      0.0142). CONCLUSIONS: A forensic examination of the retrieved components that
      failed secondary to an adverse reaction to metal debris showed, in all cases,
      visible corrosion. Of the implant and patient factors investigated, we did not
      identify any predictors of corrosion. The severity of damage was found to
      increase with time; cobalt was significantly elevated over chromium. CLINICAL
      RELEVANCE: Surgeons should scrupulously follow and consider revision for patients
      with this implant design to avoid extensive tissue excision. Blood metal ion
      tests may aid in identifying the mechanisms of taper corrosion.

PMID- 30277997
TI  - Radiographic and Clinical Outcomes of Porous Titanium-Coated and Plasma-Sprayed
      Acetabular Shells: A Five-Year Prospective Multicenter Study.
AB  - BACKGROUND: New materials in cementless total hip arthroplasty are continuously
      introduced into clinical practice. The objective of this study was to compare the
      radiographic and clinical performances of acetabular shells made with porous
      titanium coating (PTC) and plasma-sprayed titanium (PS). METHODS: Data from a
      prospective multicenter study monitoring PTC and PS shells were analyzed. Three
      hundred and eighty patients (191 with PTC and 189 with PS) with postoperative
      (within 10 months after the operation) and 5-year radiographs were available for
      assessment of radiographic outcomes and patient-reported outcome measures
      (PROMs). A radiolucent distance between the cup and acetabulum of >=0.5 mm was
      defined as a gap if it was found on a postoperative radiograph and as a
      radiolucency if it was found on a later follow-up radiograph for the first time.
      RESULTS: Postoperative gaps were more common with the PS shell (40% versus 24%, p
      < 0.001). However, a higher percentage of the gaps in the PTC group persisted at
      5 years (56% versus 4%, p < 0.001). At 5 years, 23% of the PTC shells had a
      radiolucency versus 5% of the PS shells (p < 0.001). Logistic regression revealed
      a 5.2-fold increase in the odds for radiolucency with the PTC shell (p < 0.001).
      No patient underwent revision surgery due to acetabular component loosening
      within the study period. A PTC shell was the only factor associated with the risk
      of pain in a logistic regression model (odds ratio = 2.0, p = 0.035).
      CONCLUSIONS: PTC shells were associated with more patient-reported pain and a
      higher risk of radiolucency and a persistent gap at 5 years compared with the PS
      shells, although these outcomes were not related to each other. The clinical
      relevance of the radiographic findings is unclear as no prostheses were revised
      because of loosening, but the findings warrant additional follow-up studies.
      LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 30277998
TI  - Osteosynthesis with Parallel Implants in the Treatment of Femoral Neck Fractures:
      Minimal Effect of Implant Position on Risk of Reoperation.
AB  - BACKGROUND: The purpose of this study was to estimate the incidence of
      reoperation and the effect of implant position on the risk of reoperation within
      12 months following osteosynthesis with use of parallel implants for femoral neck
      fractures. METHODS: From cases registered in the Danish Fracture Database, 1,206
      consecutive surgeries for a primary femoral neck fracture treated with use of
      parallel implants during the period of December 2011 to November 2015, and having
      available radiographs and follow-up data, were reviewed. Data included age, sex,
      time to surgery, fracture classification, and American Society of
      Anesthesiologists (ASA) score. Fracture displacement, posterior tilt, the number
      of implants, posterior distance, calcar distance, tip-cartilage distance, and
      angulation of implants were measured on pre- and postoperative radiographs. Data
      on secondary surgeries were collected from the Danish Civil Registration System.
      The effects of the included variables on the risk of reoperation were evaluated
      using Cox regression analysis. RESULTS: The median age was 73 years (range, 21 to
      102 years); in 69% of the cases, the patient was female. Two implants were used
      in 997 cases and 3 implants were used in 209. In 157 cases, the patient underwent
      reoperation within 1 year; in 228 cases, the patient died within 1 year. The
      median time to reoperation was 116 days. Patients <70 years of age were more
      likely to undergo reoperation (18.0% compared with 9.8%) but less likely to die
      (7.4% compared with 26.3%) than were patients >=70 years of age. Female sex,
      higher ASA score, and displaced fractures were associated with increased risk of
      reoperation. Time to surgery was associated with increased risk of reoperation
      for displaced fractures only. Of the variables pertaining to the osteosynthesis,
      only insufficient fracture reduction, placement of the implants with an angle to
      the shaft of <=125 degrees , and femoral head perforation significantly increased
      the risk of reoperation. We found no effect of the posterior distance, the calcar
      distance, the tip-caput distance, or whether or not the implants were parallel.
      CONCLUSIONS: Insufficient reduction, varus position of the implants, and
      perforation of the femoral head cartilage were the only surgical factors
      influencing the risk of reoperation. Sufficient fracture reduction is perhaps
      more important than focusing on an optimal position of the implants. LEVEL OF
      EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 30277999
TI  - Anterior Spinal Growth Tethering for Skeletally Immature Patients with Scoliosis:
      A Retrospective Look Two to Four Years Postoperatively.
AB  - BACKGROUND: Anterior spinal growth tethering (ASGT) has been shown to alter
      spinal growth with the potential to correct scoliosis while maintaining spine
      flexibility. The purpose of this study was to report the 2 to 4-year outcomes of
      ASGT in skeletally immature patients with thoracic scoliosis. METHODS: We
      conducted a retrospective review of patients with thoracic scoliosis who
      underwent ASGT with a minimum of 2 years of follow-up. Patient demographics,
      perioperative data, and radiographic outcomes are reported. A "successful"
      clinical outcome was defined as a residual curve of <35 degrees  and no posterior
      spinal fusion indicated or performed at latest follow-up. RESULTS: Seventeen
      patients met the inclusion criteria. The etiology was idiopathic for 14 and
      syndromic for 3. The mean follow-up was 2.5 years (range, 2 to 4 years).
      Preoperatively, all patients were at Risser stage 0, with a mean age at surgery
      of 11 +/- 2 years (range, 9 to 14 years). There was an average of 6.8 +/- 0.5
      vertebrae tethered per patient. The average thoracic curve magnitude was 52
      degrees  +/- 10 degrees  (range, 40 degrees  to 67 degrees ) preoperatively, 31
      degrees  +/- 10 degrees  immediately postoperatively, 24 degrees  +/- 17 degrees 
      at 18 months postoperatively, and 27 degrees  +/- 20 degrees  at latest follow-up
      (51% correction; range, 5% to 118%). Revision surgery was performed in 7
      patients: 4 tether removals due to complete correction or overcorrection, 1
      lumbar tether added, 1 tether replaced due to breakage, and 1 revised to a
      posterior spinal fusion. In 3 additional patients, posterior spinal fusion was
      indicated due to progression. Eight (47%) of the patients had a suspected broken
      tether. Ten (59%) of the 17 were considered clinically successful. CONCLUSIONS:
      Despite most patients having some remaining skeletal growth at the time of
      review, the results of the current study demonstrate that at mid-term follow-up,
      ASGT showed a powerful, but variable, ability to modulate spinal growth and did
      so with little perioperative and early postoperative risk. Fusion was avoided for
      13 of the 17 patients. The overall success rate was 59%, with a 41% revision
      rate. Understanding the parameters leading to success or failure will be critical
      in advancing a reliable definitive nonfusion treatment for progressive scoliosis
      in the future. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 30278000
TI  - Implementing a Postoperative Opioid-Prescribing Protocol Significantly Reduces
      the Total Morphine Milligram Equivalents Prescribed.
AB  - BACKGROUND: Opioid-prescribing patterns have been implicated as a contributing
      factor to the opioid epidemic, yet few evidence-based guidelines exist to assist
      health-care providers in assessing and possibly modifying their prescribing
      practices. METHODS: Five orthopaedic hand surgeons at a level-I trauma center
      developed a postoperative prescribing guideline for 25 common hand and upper
      extremity outpatient procedures, which were delineated into 5 tiers.
      Postoperative opioid prescriptions in a 3-month period after implementation of
      the protocol were compared with those from a 3-month period before implementation
      of the protocol. RESULTS: There were 231 patients in the pre-implementation group
      and 287 patients in the post-implementation group. Each individual opioid
      protocol tier showed a significant decrease in the mean morphine milligram
      equivalents (MME) prescribed, ranging from a minimum decrease of 97.8% to a
      maximum decrease of 176.0%. After implementation, adherence to protocol was
      achieved in 55.1% of patients; the MME amounts prescribed were below protocol for
      28.6% and above for 16.4%. The number of additional opioid prescriptions in the 1
      month postoperative period was significantly less in the post-implementation
      group than in the pre-implementation group (p < 0.001). The total number of pills
      prescribed was reduced by a theoretical equivalent of over three thousand 5-mg
      oxycodone pills for the 287 patients in the 3-month period. CONCLUSIONS: By
      utilizing a simple consensus protocol, we have demonstrated success diminishing
      the number of opioids prescribed without leading to an increase in the number of
      secondary prescriptions written by our providers. These findings are encouraging
      and suggest that fewer opioids were left in the possession of patients, leaving
      fewer pills vulnerable to misuse, abuse, and diversion.

PMID- 30278001
TI  - High-Energy Pelvic Ring Disruptions with Complete Posterior Instability:
      Contemporary Reduction and Fixation Strategies.

PMID- 30278002
TI  - What's Important: Orthopaedic Surgery and Flying-Complementary Passions.

PMID- 30278003
TI  - The 2018 American Orthopaedic Association-Japanese Orthopaedic Association (AOA
      JOA) Traveling Fellowship.

PMID- 30278004
TI  - Self-Reported Postoperative Opioid-Prescribing Practices Following Commonly
      Performed Orthopaedic Hand and Wrist Surgical Procedures: A Nationwide Survey
      Comparing Attending Surgeons and Trainees.
AB  - BACKGROUND: Although orthopaedic surgeons have been shown to prescribe excessive
      amounts of opioid analgesics postoperatively, the degree in which surgical
      trainees contribute to this trend is unknown. The purpose of this study was to
      compare self-reported opioid-prescribing behavior, factors influencing this
      behavior, and perceptions of patient opioid utilization and disposal between hand
      surgeons and trainees. METHODS: Attending hand surgeons and trainees in hand,
      orthopaedic, and plastic surgery programs were invited to participate in a web
      based survey including demographic characteristics; self-reported prescribing
      behavior specific to 4 procedures: open carpal tunnel release, trigger finger
      release, thumb carpometacarpal arthroplasty, and distal radial fracture open
      reduction and internal fixation; and perceptions and influencing factors.
      Analgesic medications were converted to morphine milligram equivalents and were
      compared across groups of interest using independent t tests or analysis of
      variance for each procedure. RESULTS: A total of 1,300 respondents (266 attending
      surgeons, 98 fellows, 708 orthopaedic residents, and 228 plastic surgery
      residents) were included. Surgeons reported prescribing fewer total morphine
      milligram equivalents compared with residents for all 4 procedures. Personal
      experience was the most influential factor for prescribing behavior by surgeons
      and fellows. Although residents reported that attending surgeon preference was
      their greatest influence, most reported no direct opioid-related communication
      with attending surgeons. CONCLUSIONS: Residents self-report prescribing
      significantly higher morphine milligram equivalents for postoperative analgesia
      following commonly performed hand and wrist surgical procedures than attending
      surgeons. Poor communication between residents and attending surgeons may
      contribute to this finding. Residents may benefit from education on opioid
      prescription, and training programs should encourage direct communication between
      trainees and attending surgeons.

PMID- 30278005
TI  - Ethics and Limb Salvage: Presenting Amputation as a Treatment Option in Lower
      Extremity Trauma.

PMID- 30278006
TI  - Minimal Effect of Implant Position on Failure Rates in Femoral Neck Fractures:
      Commentary on an article by Anne Marie Nyholm, MD, et al.: "Osteosynthesis with
      Parallel Implants in the Treatment of Femoral Neck Fractures. Minimal Effect of
      Implant Position on Risk of Reoperation".

PMID- 30278007
TI  - Vertebral Tethering for Scoliosis Management: Commentary on an article by Peter
      O. Newton, MD, et al.: "Anterior Spinal Growth Tethering for Skeletally Immature
      Patients with Scoliosis. A Retrospective Look Two to Four Years Postoperatively".

PMID- 30278008
TI  - Patient-related Risk Factors for Postoperative Stiffness Requiring Surgical
      Intervention After Arthroscopic Rotator Cuff Repair.
AB  - INTRODUCTION: Risk factors for stiffness after arthroscopic rotator cuff repair
      (RCR) have been limited to studies with small patient numbers. The objective is
      to determine patient-related risk factors for stiffness after RCR. METHODS: The
      PearlDiver database was queried from 2007 to 2015 for patients undergoing
      isolated arthroscopic RCR. A multivariate binomial logistic regression analysis
      assessed for risk factors requiring a postoperative manipulation under anesthesia
      (MUA) or lysis of adhesions (LOA) within 9 months after RCR. RESULTS: Two hundred
      thirty-two of 19,229 patients (1.2%) underwent a LOA and/or MUA within 9 months
      after arthroscopic RCR. Significant risk factors identified were age less than 50
      years (odds ratio [OR], 1.9; P < 0.0001), female gender (OR, 2.0; P < 0.0001),
      diabetes mellitus (DM) type I (OR, 2.7; P < 0.0001), hypothyroidism (OR, 1.3; P =
      0.020), and systemic lupus erythematosus (OR, 2.1; P = 0.004). However, tobacco
      use was associated with a 0.5 risk of developing stiffness (P < 0.0001).
      DISCUSSION: Systemic lupus erythematosus, hypothyroidism, and DMI (but not DMII)
      in addition to young age and female gender were risk factors for LOA/MUA after
      arthroscopic RCR.

PMID- 30278009
TI  - Glenohumeral Dislocation Arthropathy: Etiology, Diagnosis, and Management.
AB  - Dislocation arthropathy describes the development of progressive degenerative
      changes of the glenohumeral joint in the setting of instability. Although the
      specific etiology remains unclear, the trauma of a single dislocation, repetitive
      injury associated with recurrent dislocations, changes in shoulder biomechanics,
      and complications associated with instability surgery have all been implicated in
      its development. Pain and restricted range of motion are the most common patient
      complaints. Conservative management, consisting of pain control, activity
      modification, and physical therapy, is the first-line treatment after the
      development of arthropathy. If conservative management fails, multiple surgical
      options exist. Arthroscopic debridement can be attempted in young, active
      patients and in those patients with mild-to-moderate arthropathy. Open
      subscapularis lengthening and capsular release can be done in patients with prior
      instability repairs that are overly tight. In young patients with minimal bone
      loss and glenoid wear, surface replacement arthroplasty and hemiarthroplasty are
      surgical options. In older patients with moderate-to-severe arthropathy, total
      shoulder or reverse shoulder arthroplasty is the preferred treatment option.
      Further study is needed to better predict which patients will develop dislocation
      arthropathy and will thus benefit from early surgical intervention.

PMID- 30278010
TI  - Diagnosing Sacroiliac Joint Pain.
AB  - The sacroiliac joint (SIJ) is a diarthrodial joint that has been implicated as a
      pain generator in approximately 10% to 25% of patients with mechanical low back
      or leg symptoms. Unique anatomic and physiologic characteristics of SIJ make it
      susceptible to mechanical stress and also create challenges in the diagnosis of
      SIJ pain. A variety of inciting causes for SIJ pain may exist, ranging from
      repetitive low-impact activities such as jogging to increased stress after
      multilevel spine fusion surgery to high-energy trauma such as in motor vehicle
      accidents. Similarly, wide variability exists in the clinical presentation of SIJ
      pain from localized pain or tenderness around the SIJ to radiating pain into the
      groin or even the entire lower extremity. No pathognomonic clinical history,
      physical examination finding, or imaging study exists that aids clinicians in
      making a reliable diagnosis. However, imaging combined with clinical provocative
      tests might help to identify patients for further investigation. Although
      provocative physical examination tests have not received reliable consensus, if
      three or more provocative tests are positive, pursuing a diagnostic SIJ injection
      is considered reasonable. Notable pain relief with intra-articular anesthetic
      injection under radiographic guidance has been shown to provide reliable evidence
      in the diagnosis of SIJ pain.

PMID- 30278011
TI  - The In Vitro Effects of Bupivacaine on Cartilage-forming Tumor Cells.
AB  - INTRODUCTION: Bupivacaine is a commonly used local anesthetic that has been shown
      to be cytotoxic to articular chondrocytes and various tumor cells. This study
      evaluates the in vitro effects of bupivacaine on cartilaginous tumor cells.
      METHODS: Multiple different cartilaginous tumors were evaluated, including
      enchondromas, chondroblastomas, a low-grade chondrosarcoma, which were harvested
      from patients during tumor resection, and a grade-II chondrosarcoma SW1535 (ATCC
      HTB-94). The tumor cells were treated with 0.25% and 0.5% bupivacaine at various
      times points, and the result was compared with that of untreated tumor cells.
      Tumor cell viability and apoptosis were evaluated by MTT (3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyl tetrazolium bromide) assay and flow cytometry. RESULTS: The
      tumors were analyzed in groups according to their pathologic diagnosis.
      Increasing periods of exposure to bupivacaine decreased the cell viability in all
      tumor samples. The cytotoxicity of 0.5% bupivacaine was significantly greater
      than that of 0.25% bupivacaine in all tumor cells tested. DISCUSSION: At
      clinically relevant concentrations, in vitro exposure to bupivacaine caused a
      decrease in cellular viability and an increase in the induction of apoptosis in a
      dose- and time-dependent manner in each of the tumor cells evaluated in this
      study.

PMID- 30278012
TI  - Management of Isolated Lateral Malleolus Fractures.
AB  - Isolated lateral malleolus fractures represent one of the most common injuries
      encountered by orthopaedic surgeons. Nevertheless, appropriate diagnosis and
      management of these injuries are not clearly understood. Ankle stability is
      maintained by ligamentous and bony anatomy. The deep deltoid ligament is
      considered the primary stabilizer of the ankle. In the setting of an isolated
      lateral malleolus fracture, identifying injury to this ligament and associated
      ankle instability influences management. The most effective methods for assessing
      tibiotalar instability include stress and weight-bearing radiographs. Clinical
      examination findings are important but less reliable. Advanced imaging may not be
      accurate for guiding management. If the ankle is stable, nonsurgical management
      produces excellent outcomes. In the case that clinical/radiographic findings are
      indicative of ankle instability, surgical fixation options include lateral or
      posterolateral plating or intramedullary fixation. Locking plates and small or
      minifragment fixation are important adjuncts for the surgeon to consider based on
      individual patient needs.

PMID- 30278013
TI  - Latissimus Dorsi Tendon Rupture.
AB  - Isolated injury to the latissimus dorsi is rare. Partial tendon tears may be
      successfully treated nonsurgically. Complete tendon ruptures require surgical
      repair. Tendon repair can be approached either through an anterior deltopectoral
      incision with a secondary small posterior axillary incision or through a long
      posterior axillary incision. Suture anchors can be used to repair the latissimus
      dorsi to the humeral attachment. Although the literature is limited to single
      patient case series, most patients have returned to full athletic activity after
      surgical repair.

PMID- 30278014
TI  - Revisiting the Gender Gap in Orthopaedic Surgery: Investigating the Relationship
      Between Orthopaedic Surgery Female Faculty and Female Residency Applicants.
AB  - INTRODUCTION: Although women now constitute approximately half of all graduating
      medical students, orthopaedic surgery continues to lag behind in its ability to
      recruit female applicants. One hypothesis for this discrepancy is the lack of
      female faculty mentors at academic institutions. The three objectives of this
      study were the following: (1) to quantify the proportion of female orthopaedic
      surgery residency applicants, (2) to quantify the proportion of female
      orthopaedic surgery faculty, and (3) to investigate the relationship between
      female orthopaedic surgery faculty at an academic institution and the
      corresponding number of female orthopaedic surgery residency applicants. METHODS:
      Data from the Association of American Medical Colleges from 2005 to 2014 were
      used to calculate the number of medical school graduates, the number of
      orthopaedic surgery residency applicants, and the number of orthopaedic full-time
      faculty in the United States. Institutions were excluded if they had incomplete
      data. A Spearman rank correlation was used to assess for a correlation between
      the 9-year total number of female orthopaedic surgery applicants and the average
      number of female orthopaedic surgery faculty members. RESULTS: A total of 101
      U.S. medical schools were included in the final analysis. During the period
      examined, women accounted for 48.7% of medical school graduates, 14.9% of
      orthopaedic surgery applicants, and 13.2% of full-time orthopaedic surgery
      faculty. The percentage of female residency applicants increased from 13.91% in
      2005 to 2006 to 16.02% in 2013 to 2014 while the percentage of female faculty
      increased from 12.26% in 2005 to 2006 to 15.79% in 2013 to 2014. No correlation
      was found between the average number of female orthopaedic surgery faculty at an
      institution and the total number of female orthopaedic surgery applicants from
      that institution during the study period examined (Rho, 0.0176; P = 0.5957).
      CONCLUSIONS: The data presented in this study failed to demonstrate a
      relationship between the number of female faculty and the number of women who
      apply into orthopaedic surgery, which highlights the complex nature of this
      issue. More research is needed to examine factors influencing the recruitment of
      female medical students.

PMID- 30278015
TI  - Cost Comparison of Femoral Distraction Osteogenesis With External Lengthening
      Over a Nail Versus Internal Magnetic Lengthening Nail.
AB  - INTRODUCTION: Femoral lengthening is performed by distraction osteogenesis via
      lengthening over a nail (LON) or by using a magnetic lengthening nail (MLN). MLN
      avoids the complications of external fixation while providing accurate and easily
      controlled lengthening. However, the increased cost of implants has led many to
      question whether MLN is cost-effective compared with LON. METHODS: A
      retrospective review was performed comparing consecutive femoral lengthenings
      using either LON (n = 19) or MLN (n = 39). The number of surgical procedures,
      time to union, and amount of lengthening were compared. Cost analysis was
      performed using both hospital and surgeon payments. Costs were adjusted for
      inflation using the Consumer Price Index. RESULTS: No difference was observed in
      the length of femoral distraction. Patients treated with MLN underwent fewer
      surgeries (3.1 versus 2.1; P < 0.001) and had a shorter time to union (136.7
      versus 100.2 days; P = 0.001). Total costs were similar ($50,255 versus $44,449;
      P = 0.482), although surgeon fees were lower for MLN ($4,324 versus $2,769; P <
      0.001). DISCUSSION: Although implants are more expensive for MLN than LON, this
      appears to be offset by fewer procedures. Overall, the two procedures had similar
      total costs, but MLN was associated with a decreased number of procedures and
      shorter time to union. LEVEL OF EVIDENCE: III.

PMID- 30278016
TI  - Clinical Practice Guidelines in Action: Differences in Femoral Neck Fracture
      Management by Trauma and Arthroplasty Training.
AB  - INTRODUCTION: The purpose of this study was to survey trauma and arthroplasty
      surgeons to investigate associations between subspecialty training and management
      of geriatric femoral neck fractures and to compare treatments with the American
      Academy of Orthopaedic Surgeons clinical practice guidelines. METHODS: Five
      hundred fifty-six surgeons completed the online survey consisting of two
      sections: (1) surgeon demographics and (2) two geriatric hip fracture cases with
      questions regarding treatment decisions. RESULTS: In both clinical scenarios,
      arthroplasty surgeons were more likely than trauma surgeons to recommend total
      hip arthroplasty (THA) (case 1: 96% versus 84%; case 2: 29% versus 10%; P <=
      0.02) and spinal anesthesia (case 1: 70% versus 40%; case 2: 62% versus 38%; P <
      0.01). Surgeons who have made changes based on clinical practice guidelines (n =
      96; 21% of surveyed) cited more use of THA (n = 56; 58% of respondents) and
      cemented stems (n = 28; 29% of respondents). CONCLUSION: Arthroplasty surgeons
      are more likely to recommend THA over hemiarthroplasty and have a higher
      expectation for spinal anesthesia for the management of geriatric femoral neck
      fractures.

PMID- 30278017
TI  - Electrical Injuries of the Hand and Upper Extremity.
AB  - High-voltage electrical injuries are relatively rare injuries that pose unique
      challenges to the treating physician, yet the initial management follows well
      established life-saving, trauma- and burn-related principles. The upper
      extremities are involved in most electrical injuries because they are typically
      the contact points to the voltage source. The amount of current that passes
      through a specific tissue is inversely proportional to the tissue's intrinsic
      resistance with electricity predominantly affecting the skeletal muscle secondary
      to its large volume in the upper extremity. Therefore, cutaneous burns often
      underestimate the true extent of the injury because most current is through the
      deep tissues. Emergent surgical exploration is reserved for patients with
      compartment syndrome; otherwise, initial debridement can be delayed for 24 to 48
      hours to allow tissue demarcation. Early rehabilitation, wound coverage, and
      delayed deformity reconstruction are important concepts in treating electrical
      injuries.

PMID- 30278018
TI  - Label-free Identification of Antibody-mediated Rejection in Cardiac Allograft
      Biopsies Using Infrared Spectroscopic Imaging.
AB  - BACKGROUND: Antibody-mediated rejection (AMR) in cardiac allograft recipients
      remains less well-understood than acute cellular rejection, is associated with
      worse outcomes, and portends a greater risk of developing chronic allograft
      vasculopathy. Diffuse immunohistochemical (IHC) C4d staining of capillary
      endothelia in formalin-fixed, paraffin-embedded (FFPE) right ventricular (RV)
      endomyocardial biopsies is diagnostic of immunopathologic AMR but serves more as
      a late-stage marker. Infrared (IR) spectroscopy may be a useful tool in earlier
      detection of rejection. We performed mid-IR spectroscopy to identify a unique
      biochemical signature for AMR. METHODS: A total of 30 posttransplant FFPE RV
      tissue biopsies (14 positive for C4d and 16 negative for C4d) and 14 native heart
      biopsies were sectioned for IR analysis. IR images of entire sections were
      acquired and regions of interest (ROI) from cardiomyocytes were identified.
      Extracted spectra were averaged across many pixels within each ROI. Principal
      component analysis coupled with linear discriminant analysis (PCA-LDA) and
      predictive classifiers were applied to the data. RESULTS: Comparison of averaged
      mid-IR spectra revealed unique features among C4d-positive, C4d-negative, and
      native heart biopsies. PCA-LDA and classification models demonstrated that
      spectral features from the mid-IR fingerprint region of these 3 groups permitted
      accurate automated classification into each group. CONCLUSIONS: In cardiac
      allograft biopsies with immunopathologic AMR, IR spectroscopy reveals a
      biochemical signature unique to AMR compared to that of nonrejecting cardiac
      allografts and native hearts. Future study will focus on the predictive
      capabilities of this IR signature.

PMID- 30278019
TI  - An Update on the Management of Adult Traumatic Nerve Injuries-Replacing Old
      Paradigms: A Review.
AB  - Acute nerve injuries are routinely encountered in multisystem trauma patients.
      Advances in surgical treatment of nerve injuries now mean that good outcomes can
      be achieved. Despite this, old mantras associated with management of nerve
      injuries, including "wait a year to see if recovery occurs" and "there's nothing
      we can do", persist. Practicing by these mantras places these patients at a
      disadvantage.Changes begin to occur in the nerve, neuromuscular junction, and
      muscle from the moment a nerve injury occurs. These changes can become
      irreversible approximately 18-24 months following denervation. Thus, it is a race
      to reestablish a functional nerve-muscle connection prior to these irreversible
      changes. Good outcomes rely on appropriate acute management and avoiding delays
      in care. Primary nerve surgery options include direct primary repair, nerve graft
      repair, and nerve transfer. Acute management of nerve injuries proceeds according
      to the rule of 3s and requires early cooperation between trauma surgeons who
      recognize the nerve injury and consultant nerve surgeons.Care of patients with
      acute, traumatic nerve injuries should not be delayed. Awareness of current
      management paradigms among trauma surgeons will help facilitate optimal upfront
      management. With the ever-expanding surgical options for management of these
      injuries and the associated improvement of outcomes, early multidisciplinary
      approaches to these injuries has never been more important. Old mantras must be
      replaced with new paradigms in order to continue to see improvements in outcomes
      for these patients. The importance of this review is to raise awareness among
      trauma surgeons of new paradigms for management of traumatic nerve injuries.

PMID- 30278020
TI  - Does the incidence of thoracic aortic injury warrant the routine use of chest
      computed tomography in children?
AB  - BACKGROUND: Thoracic aortic injury is a potentially life-threatening injury
      associated with rapid deceleration mechanisms. Diagnosis is made by chest
      computed tomography (CT), which is associated with a risk of radiation-induced
      malignancy. We sought to determine the incidence of aortic injuries in the
      pediatric population to weigh against the risk of CT imaging. METHODS: The
      Pediatric Health Information Systems (PHIS) was queried for children <=18 years
      with discharge diagnosis code of thoracic aortic injury (901.0) between December
      2004 and 2014. Data abstracted included patient age, gender, diagnosis and
      procedure codes, and discharge disposition, where available. We also queried for
      imaging codes to determine what type of chest imaging the child received.
      RESULTS: Between December 2004 and 2014, 311,850 children were admitted to PHIS
      hospitals with traumatic injury. Of these patients, 46 (0.015%) were coded with a
      thoracic aortic injury and an accompanying E-code. Twenty-seven patients (58.7%)
      were male and the median age was 13 years. The most common mechanism of injury
      was motor vehicle collision (63%, n=29). Eighteen hospitals (41.9%) had no
      patients with a thoracic aortic injury in the 10-year period. In children with a
      thoracic aortic injury the mortality rate was 11% (n=5) and 22 (47.8%) underwent
      a chest CT during their hospitalization. Forty percent (124,909) of all trauma
      patients underwent chest CT, with a positive rate for aortic injury of
      1.8/10,000. The reported estimated cancer risk from a chest CT scan is 25/10,000
      for girls and 7.5/10, 000 in boys, greater than the positive CT rate. 3
      CONCLUSION: Thoracic aortic injuries are rare in children in the United States.
      The risk of cancer associated with screening chest CT is greater than the
      likelihood of identifying an aortic injury. Therefore, screening chest CT scans
      are unwarranted in injured children. LEVEL OF EVIDENCE: III (prognostic and
      epidemiological).

PMID- 30278021
TI  - Letter about "Impact of Licensed Federal Firearm Suppliers on Firearm-Related
      Mortality," which has been published online ahead of print.

PMID- 30278022
TI  - Challenges, Opportunities, Unity, and Global Engagement: The 2017 AAST
      Presidential Address.

PMID- 30278023
TI  - Establishing the First Hartford Consensus-Compliant Medical School in the USA.
AB  - BACKGROUND: Following the Hartford Consensus meetings, the Stop the Bleed
      Campaign was created to reduce the prevalence of death from exsanguination in the
      case of traumatic hemorrhage. The campaign revolves around providing hemorrhage
      control training to members of the public and increasing public access to
      hemorrhage control equipment. To our knowledge, no medical school has established
      a self-sustaining Stop the Bleed program to train their students and faculty as
      well as made hemorrhage control equipment available for use in an emergency.
      METHODS: Bleeding Control classes were offered at the Frank H. Netter MD School
      of Medicine beginning in January 2018. A proposal was made to the medical
      school's Council on Curriculum Oversight in May 2018 to incorporate the training
      as part of the required curriculum for first-year students. A second proposal was
      made to Quinnipiac University's Emergency Management Team in June 2018 to
      purchase hemorrhage control equipment. RESULTS: Twelve bleeding control courses
      were held between January and August 2018. Two hundred and ten medical students,
      19 faculty members, and 36 public safety officers completed initial training.
      Thirty-four medical students, two faculty members, and two public safety officers
      became certified instructors. Training was incorporated into the first-year
      curriculum to be taught by certified second-year students under the direction of
      the school's Department of Surgery. The school purchased approved training
      equipment. A student-coordinator position was created in the Surgery Interest
      Group. Hemorrhage control equipment was purchased for each public safety officer,
      patrol vehicles, and for the Central Dispatch headquarters. Public-access
      equipment has been purchased for each Automated External Defibrillator cabinet at
      the medical school. CONCLUSIONS: The School of Medicine community has been
      empowered with the ability to save lives. Students and faculty have been trained
      in life-saving skills, a self-sustaining training process has been created, and
      equipment has been purchased for hemorrhage control efforts. LEVEL OF EVIDENCE:
      Level II, Economic & Value-based Evaluation.

PMID- 30278024
TI  - Future strategies for remote damage control resuscitation after traumatic
      hemorrhage.
AB  - : One of the key elements of remote damage control resuscitation (RDCR) is a
      hemostatic resuscitation strategy to prevent the triad of coagulopathy, acidosis
      and hypothermia. Transfusion of whole blood has been an effective solution for
      both military and civilian patients, and appears to be superior to individual
      component therapy. At first, whole blood seems to be the ideal solution for RDCR,
      but it has some clinical and logistic drawbacks that may limit its use in the
      prehospital, battlefield, austere, and remote settings, or during multiple
      casualty or massive transfusion scenarios. The ideal resuscitation product for
      RDCR after traumatic hemorrhagic shock would be light-weight, long lasting,
      easily stored in large quantities, free from refrigeration, carry no risk of
      blood-borne infection or ABO-incompatibility, and carry out the same
      physiological functions as blood. Lyophilized plasma appears to fulfil many of
      these criteria, and is in current clinical use. There have been promising
      preclinical investigations of haemoglobin-based oxygen carriers (HBOC) and
      lyophilized platelet preparations, and one HBOC is in clinical use. It seems
      feasible that in the near future there may be a total blood substitution strategy
      for RDCR that is priority based, aimed at repaying the oxygen debt, restoration
      of the endothelium, and mitigation of coagulopathy and inflammatory
      dysregulation. Further preclinical and clinical research activity may facilitate
      such a resuscitation strategy that is equivalent-or perhaps even superior-to
      whole blood, but without any of its drawbacks. TYPE OF ARTICLE: Current opinion
      LEVEL OF EVIDENCE: Not applicable.

PMID- 30278025
TI  - Endovascular Control of Pelvic Hemorrhage: Concomitant use of REBOA and
      Endovascular Intervention.

PMID- 30278027
TI  - Lymphogranuloma venereum: an increasingly common anorectal infection among men
      who have sex with men attending New York City Sexual Health Clinics.
AB  - Using Chlamydia trachomatis anorectal specimens routinely tested for LGV (2008
      2011) and samples of archived specimens tested for LGV (2012-2015), we observed
      increased LGV positivity among men-who-have-sex-with-men attending NYC Sexual
      Health Clinics. Using clinical data, we determined predictors of anorectal LGV
      that may guide clinical management.

PMID- 30278026
TI  - Associations Between Cannabis Use, Sexual Behavior, and STIs/HIV in a Cohort of
      Young Men Who Have Sex with Men.
AB  - BACKGROUND: Among men who have sex with men (MSM) the relationship between
      sexually transmitted infections (STIs) and cannabis use is not well established.
      We assessed cannabis use, sexual behavior, and STIs including HIV in a diverse
      cohort of young MSM. METHODS: In Los Angeles the mSTUDY cohort conducted visits
      every 6 months with 512 MSM between 2014 and 2017 collecting demographics, sexual
      behaviors, and reports of frequency of substance use. Each visit conducted
      testing for gonorrhea, chlamydia and syphilis via blood, urine, and pharyngeal
      and rectal swabs by PCR, HIV was assessed using rapid tests for HIV negatives and
      viral load for HIV positives. We analyzed the relationship between cannabis use,
      sexual behaviors and STIs/HIV across 1,535 visits. RESULTS: Significantly fewer
      participants tested positive for STIs at visits when reporting the previous 6
      months use of only cannabis (11.7%) compared to no drugs (16.3%) or other drugs
      (20.0%), (p=0.01). Fewer MSM reporting only cannabis use than no or other drug
      use had been incarcerated, had incarcerated partners, experienced interpersonal
      violence, and were HIV positive. In multivariable analyses visits with positive
      STIs were associated with other drug use (adjusted odds ratio (AOR) 1.69, 95% CI
      (1.03-2.78)) but not use of cannabis only or no drug use after controlling for
      age, HIV status, new sex partners, and number of sex partners. CONCLUSIONS: When
      MSM reported using cannabis exclusively fewer STIs were detected and lower risk
      sexual engagements reported than when MSM reported no drug or other drug use.

PMID- 30278028
TI  - Individual and Neighborhood Factors Associated with Sexual Behavior Classes in an
      Urban Longitudinal Sample.
AB  - BACKGROUND: This study aimed to increase understanding of the clustering of
      sexual behaviors in an urban sample of emerging adults, and the individual and
      neighborhood factors associated with sexual behavior patterns in order to provide
      insight into reducing the disproportionate burden of poor sexual outcomes among
      urban African Americans. METHODS: We draw on two cohorts of urban, predominantly
      African American youth first assessed at age 6 and follow-up to emerging
      adulthood (mean age 20, n=1,618). Latent class analyses by gender identified co
      occurrence of sexual behavior. RESULTS: We found three classes for both males and
      females: high-risk (13% of males, 15% of females), low-risk (54% of males, 56% of
      females) and no-risk (33% of males, 29% of females). Membership in the high-risk
      class was associated with school dropout, a substance use disorder diagnosis,
      having a criminal arrest, pregnancy, and STDs for both males and females. High
      risk females also had higher rates of depression. Low-risk males and females also
      had elevated risk of pregnancy and parenthood. Neighborhood factors distinguished
      the high- and no-risk classes for males and females, including the neighborhood
      environment scale, which assessed poverty, safety, drug activity, and
      crime/violence in the neighborhood. Neighborhood religiosity was inversely
      associated with membership in the high-risk class compared to the no-risk class
      for females only. Neighborhood racism distinguished those in the high-risk class
      compared to the no-risk class for males. CONCLUSION: Future work should take into
      account the clustering of sexual risk behaviors. Specific neighborhood factors
      could be addressed to reduce sexual health disparities.

PMID- 30278029
TI  - Development of a Sexually Transmitted Disease (STD) Client-Friendly Unit at a
      Primary Care Clinic in Malaysia: Lessons Learnt.
AB  - Management of sexually transmitted diseases (STDs) and HIV is challenging due to
      the social stigma attached. We describe the development of a client-friendly STD
      service in a primary care clinic in Malaysia with a special focus on key
      populations. Challenges and key lessons learnt from its development and
      implementation are discussed.

PMID- 30278030
TI  - Chlamydia, Gonorrhea, and HIV Infection among Transgender Women and Transgender
      Men Attending Clinics That Provide STD Services in Six US Cities: Results from
      the STD Surveillance Network.
AB  - BACKGROUND: Transgender women and transgender men are disproportionately affected
      by HIV infection and may be vulnerable to other STDs, but the lack of
      surveillance data inclusive of gender identity hinders prevention and
      intervention strategies. METHODS: We analyzed data from 506 transgender women
      (1,045 total visits) and 120 transgender men (209 total visits) who attended 26
      publicly funded clinics that provide STD services in six US cities during a 3.5
      year observation period. We used clinical and laboratory data to examine the
      proportion of transgender women and transgender men who tested positive for
      urogenital and extragenital chlamydial or gonococcal infections and who self
      reported or tested positive for HIV infection during the observation period.
      RESULTS: Of the transgender women tested, 13.1% tested positive for chlamydia and
      12.6% tested positive for gonorrhea at one or more anatomic sites, and 14.2% were
      HIV-infected. Of transgender men tested, 7.7% and 10.5% tested positive for
      chlamydia and gonorrhea at one or more anatomic sites, and 8.3% were HIV
      infected., Most transgender women (86.0% and 80.9%, respectively) and more than a
      quarter of transgender men (28.6% and 28.6%, respectively) with an extragenital
      chlamydial or gonococcal infection had a negative urogenital test at the same
      visit. CONCLUSIONS: Publicly funded clinics providing STD services are likely an
      important source of STD care for transgender persons. More data are needed to
      understand the most effective screening approaches for urogenital, rectal, and
      pharyngeal CT and GC infections in transgender populations.

PMID- 30278031
TI  - Device or target? A paradigm shift in airway management: Implications for
      guidelines, clinical practice and teaching.

PMID- 30278032
TI  - Haemodynamic evaluation and optimisation of brain-dead donors with oesophageal
      Doppler during organ harvesting: A feasibility study.

PMID- 30278033
TI  - Comparison of noninvasive and minimally invasive pulse contour analysis to
      measure stroke volume during major surgery: A prospective observational study.

PMID- 30278034
TI  - Postoperative stroke: The picture is out of focus.

PMID- 30278035
TI  - The role of pre-operative alpha-blockade in patients with normotensive
      phaeochromocytoma or paraganglioma: A retrospective cohort study.

PMID- 30278036
TI  - Diosmetin Attenuates Akt Signaling Pathway by Modulating Nuclear Factor Kappa
      Light-Chain-Enhancer of Activated B Cells (NF-kappaB)/Inducible Nitric Oxide
      Synthase (iNOS) in Streptozotocin (STZ)-Induced Diabetic Nephropathy Mice.
AB  - BACKGROUND We evaluated the nephroprotective effect of diosmetin in
      streptozotocin (STZ)-induced diabetic nephropathy (DN) mice. MATERIAL AND METHODS
      Diabetes was induced by injecting STZ (50 mg/kg) i.p. for 5 days. Biochemical
      parameters, such as fasting blood glucose, creatinine, BUN in the serum, and
      albumin in the urine, were determined in STZ-induced DN mice after the 8th week
      of STZ administration. The level of inflammatory mediators in the serum and
      oxidative stress parameters in the tissue homogenate was estimated in STZ-induced
      DN mice. Expressions of Akt, NF-kappaB, and iNOS in the tissue homogenate were
      assessed by Western blot analysis. RESULTS Our data reveal that treatment with
      diosmetin significantly reduces the fasting blood glucose (FBG), serum
      creatinine, and blood urea nitrogen (BUN) in the serum and albumin in urine
      compared to the negative control group. Treatment with diosmetin attenuated the
      altered level of oxidative stress parameters and inflammatory cytokines in the
      STZ-induced DN mice. Expression of Akt and nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB) was significantly reduced and inducible
      nitric oxide synthase (iNOS) was enhanced in the tissue homogenate of diosmetin
      treated mice compared to the negative control group. Data from
      immunohistochemical analysis suggest that the expressions of NF-kappaB was
      significantly reduced in tissues of the diosmetin-treated group compared to the
      negative control group. CONCLUSIONS Our study shows that diosmetin protects
      against renal injury in STZ-induced diabetic nephropathy mice by modulating the
      Akt/NF-kappaB/iNOS signaling pathway.

PMID- 30278037
TI  - Is adaptive therapy natural?
AB  - Research suggests that progression-free survival can be prolonged by integrating
      evolutionary principles into clinical cancer treatment protocols. The goal is to
      prevent or slow the proliferation of resistant malignant cell populations. The
      logic behind this therapy relies on ecological and evolutionary processes. These
      same processes would be available to natural selection in decreasing the
      probability of an organism's death due to cancer. We propose that organisms'
      anticancer adaptions include not only ones for preventing cancer but also ones
      for directing and retarding the evolution of life-threatening cancer cells. We
      term this last strategy natural adaptive therapy (NAT). The body's NAT might
      include a lower than otherwise possible immune response. A restrained immune
      response might forego maximum short-term kill rates. Restraint would forestall
      immune-resistant cancer cells and produce long-term durable control of the cancer
      population. Here, we define, develop, and explore the possibility of NAT. The
      discovery of NAT mechanisms could identify new strategies in tumor prevention and
      treatments. Furthermore, we discuss the potential risks of immunotherapies that
      force the immune system to ramp up the short-term kill rates of malignant cancer
      cells in a manner that undermines the body's NAT and accelerates the evolution of
      immune resistance.

PMID- 30278038
TI  - Cryptochrome: The magnetosensor with a sinister side?
AB  - Over the last three decades, evidence has emerged that low-intensity magnetic
      fields can influence biological systems. It is now well established that
      migratory birds have the capacity to detect the Earth's magnetic field; it has
      been reported that power lines are associated with childhood leukemia and that
      pulsed magnetic fields increase the production of reactive oxidative species
      (ROS) in cellular systems. Justifiably, studies in this field have been viewed
      with skepticism, as the underlying molecular mechanisms are unknown. In the
      accompanying paper, Sherrard and colleagues report that low-flux pulsed
      electromagnetic fields (PEMFs) result in aversive behavior in Drosophila larvae
      and ROS production in cell culture. They further report that these responses
      require the presence of cryptochrome, a putative magnetoreceptor. If correct, it
      is conceivable that carcinogenesis associated with power lines, PEMF-induced ROS
      generation, and animal magnetoreception share a common mechanistic basis.

PMID- 30278040
TI  - In an unhealthy food system, what role should SNAP play?
AB  - In a Perspective, Hilary Seligman and Sanjay Basu discuss future scenarios of
      food assistance programs to improve population health in a changing political
      environment.

PMID- 30278039
TI  - Familiarity modulates social approach toward stressed conspecifics in female
      rats.
AB  - Familiarity between conspecifics may influence how social affective cues shape
      social behaviors. In a social affective preference test, experimental rats, when
      given the choice to explore an unfamiliar stressed or a naive adult, will avoid
      interaction with a stressed conspecific. To determine if familiarity would
      influence social interactions with stressed conspecifics, male and female test
      rats underwent 2 social affective preference tests in isosexual triads where an
      experimental rat was presented with a naive and a stressed target conspecific who
      were either familiar (cagemate) or unfamiliar. Male and female experimental rats
      avoided stressed unfamiliar conspecifics. However, experimental female rats
      demonstrated a preference to interact with their stressed, familiar cagemates.
      Male and female rats exhibited more self-grooming and immobility behavior in the
      presence of stressed conspecifics, which may indicate emotion contagion. These
      findings suggest a sex-specific role of familiarity in social approach and
      avoidance, and warrant further mechanistic exploration.

PMID- 30278041
TI  - A nested compartmental model to assess the efficacy of paratuberculosis control
      measures on U.S. dairy farms.
AB  - Paratuberculosis, also known as Johne's disease (JD), is a chronic contagious
      disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP). The disease
      is incurable, fatal and causes economic losses estimated to exceed 200 million
      dollars to the U.S. dairy industry annually. Several preventive and control
      measures have been recommended; however, only a few of these measures have been
      validated empirically. Using a nested compartmental (NC) modeling approach, the
      main objective of this research was to identify the best combination of control
      and preventive measures that minimizes the prevalence and incidence of JD and the
      risk of MAP occurrence in a dairy herd. The NC model employs both MAP
      transmission estimates and data on pen movement of cattle on a dairy to quantify
      the effectiveness of control and preventive measures. To obtain reasonable ranges
      of parameter values for between-pen movements, the NC model was fitted to the
      movement data of four typical California dairy farms. Using the estimated ranges
      of the movement parameters and those of JD from previous research, the basic
      reproduction number was calculated to measure the risk of MAP occurrence in each
      pen environment as well as the entire dairy. Although the interventions evaluated
      by the NC model were shown to reduce the infection, no single measure alone was
      capable of eradicating the infection. The numerical simulations suggest that a
      combination of test and cull with more frequent manure removal is the most
      effective method in reducing incidence, prevalence and the risk of MAP
      occurrence. Other control measures such as limiting calf-adult cow contacts,
      raising calves in a disease-free herd or colostrum management were less
      effective.

PMID- 30278043
TI  - Feeding ecology of fishes associated with artificial reefs in the northwest Gulf
      of Mexico.
AB  - The feeding ecology of two reef fishes associated with artificial reefs in the
      northwest Gulf of Mexico (GoM) was examined using gut contents and natural stable
      isotopes. Reefs were divided into three regions (east, central, west) across an
      east to west gradient of increasing reef complexity and salinity. Gray
      triggerfish (Balistes capriscus) primarily consumed reef-associated prey (xanthid
      crabs, bivalves, barnacles) and pelagic gastropods, while red snapper (Lutjanus
      campechanus) diets were mainly comprised of non-reef prey (stomatopods, fishes,
      portunid crabs). Natural stable isotopes of carbon (delta13C), nitrogen
      (delta15N), and sulfur (delta34S) were measured in consumer muscle tissue as well
      as potential primary producers. Gray triggerfish occupied a lower trophic
      position than red snapper, with lower delta13C and delta15N values across all
      size classes and regions, and generally higher delta34S values. Red snapper had a
      smaller range of stable isotope values and corrected standard ellipse areas
      across all size classes and regions, indicating a smaller isotopic niche.
      Contribution estimates of particulate organic matter (26 to 54%) and benthic
      microalgae (BMA, 47 to 74%) for both species were similar, with BMA contributions
      greater across all three size classes (juveniles, sub-adults, adults) of red
      snapper and all but the juvenile size class for gray triggerfish. Species gut
      contents and stable isotopes differed by region, with fishes consuming more crabs
      in the east region and more gastropods in the central and west regions. delta13C
      and delta15N values generally decreased from east to west, while delta34S
      increased across this gradient. Results highlight species-specific feeding
      differences associated with artificial reefs, where gray triggerfish may be more
      dependent on the reef structure for foraging opportunities. In addition, results
      offer further information on the integral role of BMA in primary production at
      nearshore artificial reefs.

PMID- 30278042
TI  - Properties of viable lyopreserved amnion are equivalent to viable cryopreserved
      amnion with the convenience of ambient storage.
AB  - Human amniotic membrane (AM) has a long history of clinical use for wound
      treatment. AM serves as a wound protective barrier maintaining proper moisture.
      AM is anti-inflammatory, anti-microbial and antifibrotic, and supports
      angiogenesis, granulation tissue formation and wound re-epithelialization. These
      properties of AM are attributed to its native extracellular matrix, growth
      factors, and endogenous cells including mesenchymal stem cells. Advances in
      tissue preservation have helped to overcome the short shelf life of fresh AM and
      led to the development of AM products for clinical use. Viable cryopreserved
      amnion (VCAM), which retains all native components of fresh AM, has shown
      positive outcomes in clinical trials for wound management. However,
      cryopreservation requires ultra-low temperature storage and shipment that limits
      widespread use of VCAM. We have developed a lyopreservation technique to allow
      for ambient storage of living tissues. Here, we compared the structural,
      molecular, and functional properties of a viable lyopreserved human amniotic
      membrane (VLAM) with properties of VCAM using in vitro and in vivo wound models.
      We found that the structure, growth factors, and cell viability of VLAM is
      similar to that of VCAM and fresh AM. Both, VCAM and VLAM inhibited TNF-alpha
      secretion and upregulated VEGF expression in vitro under conditions designed to
      mimic inflammation and hypoxia in a wound microenvironment, and resulted in wound
      closure in a diabetic mouse chronic wound model. Taken together, these data
      demonstrate that VLAM structural and functional properties are equivalent to VCAM
      but without the constraints of ultra-low temperature storage.

PMID- 30278044
TI  - Beating the odds: Sustained Chagas disease vector control in remote indigenous
      communities of the Argentine Chaco over a seven-year period.
AB  - BACKGROUND: Rapid reinfestation of insecticide-treated dwellings hamper the
      sustained elimination of Triatoma infestans, the main vector of Chagas disease in
      the Gran Chaco region. We conducted a seven-year longitudinal study including
      community-wide spraying with pyrethroid insecticides combined with periodic
      vector surveillance to investigate the house reinfestation process in connection
      with baseline pyrethroid resistance, housing quality and household mobility in a
      rural section of Pampa del Indio mainly inhabited by deprived indigenous people
      (Qom). METHODOLOGY/PRINCIPAL FINDINGS: Despite evidence of moderate pyrethroid
      resistance in local T. infestans populations, house infestation dropped from
      31.9% at baseline to 0.7% at 10 months post-spraying (MPS), with no triatomine
      found at 59 and 78 MPS. Household-based surveillance corroborated the rare
      occurrence of T. infestans and the house invasion of other four triatomine
      species. The annual rates of loss of initially occupied houses and of household
      mobility were high (4.6-8.0%). Housing improvements did not translate into a
      significant reduction of mud-walled houses and refuges for triatomines because
      most households kept the former dwelling or built new ones with mud walls.
      CONCLUSIONS/SIGNIFICANCE: Our results refute the assumption that vector control
      actions performed in marginalized communities of the Gran Chaco are doomed to
      fail. The larger-than-expected impacts of the intervention program were likely
      associated with the combined effects of high-coverage, professional insecticide
      spraying followed by systematic vector surveillance-and-response, broad
      geographic coverage creating a buffer zone, frequent housing replacement and
      residential mobility. The dynamical interactions among housing quality, mobility
      and insecticide-based control largely affect the chances of vector elimination.

PMID- 30278045
TI  - Low-intensity electromagnetic fields induce human cryptochrome to modulate
      intracellular reactive oxygen species.
AB  - Exposure to man-made electromagnetic fields (EMFs), which increasingly pollute
      our environment, have consequences for human health about which there is
      continuing ignorance and debate. Whereas there is considerable ongoing concern
      about their harmful effects, magnetic fields are at the same time being applied
      as therapeutic tools in regenerative medicine, oncology, orthopedics, and
      neurology. This paradox cannot be resolved until the cellular mechanisms
      underlying such effects are identified. Here, we show by biochemical and imaging
      experiments that exposure of mammalian cells to weak pulsed electromagnetic
      fields (PEMFs) stimulates rapid accumulation of reactive oxygen species (ROS), a
      potentially toxic metabolite with multiple roles in stress response and cellular
      ageing. Following exposure to PEMF, cell growth is slowed, and ROS-responsive
      genes are induced. These effects require the presence of cryptochrome, a putative
      magnetosensor that synthesizes ROS. We conclude that modulation of intracellular
      ROS via cryptochromes represents a general response to weak EMFs, which can
      account for either therapeutic or pathological effects depending on exposure.
      Clinically, our findings provide a rationale to optimize low field magnetic
      stimulation for novel therapeutic applications while warning against the
      possibility of harmful synergistic effects with environmental agents that further
      increase intracellular ROS.

PMID- 30278047
TI  - Should police have access to genetic genealogy databases? Capturing the Golden
      State Killer and other criminals using a controversial new forensic technique.
AB  - On April 24, 2018, a suspect in California's notorious Golden State Killer cases
      was arrested after decades of eluding the police. Using a novel forensic
      approach, investigators identified the suspect by first identifying his relatives
      using a free, online genetic database populated by individuals researching their
      family trees. In the wake of the case, media outlets reported privacy concerns
      with police access to personal genetic data generated by or shared with genealogy
      services. Recent data from 1,587 survey respondents, however, provide preliminary
      reason to question whether such concerns have been overstated. Still, limitations
      on police access to genetic genealogy databases in particular may be desirable
      for reasons other than current public demand for them.

PMID- 30278046
TI  - Multimodal MRI suggests that male homosexuality may be linked to cerebral midline
      structures.
AB  - The neurobiology of sexual preference is often discussed in terms of cerebral sex
      dimorphism. Yet, our knowledge about possible cerebral differences between
      homosexual men (HoM), heterosexual men (HeM) and heterosexual women (HeW) are
      extremely limited. In the present MRI study, we addressed this issue
      investigating measures of cerebral anatomy and function, which were previously
      reported to show sex difference. Specifically, we asked whether there were any
      signs of sex atypical cerebral dimorphism among HoM, if these were widely
      distributed (providing substrate for more general 'female' behavioral
      characteristics among HoM), or restricted to networks involved in self
      referential sexual arousal. Cortical thickness (Cth), surface area (SA),
      subcortical structural volumes, and resting state functional connectivity were
      compared between 30 (HoM), 35 (HeM) and 38 (HeW). HoM displayed a significantly
      thicker anterior cingulate cortex (ACC), precuneus, and the left occipito
      temporal cortex compared to both control groups. These differences seemed
      coordinated, since HoM also displayed stronger cortico-cortical covariations
      between these regions. Furthermore, functional connections within the default
      mode network, which mediates self- referential processing, and includes the ACC
      and precuneus were significantly weaker in HoM than HeM and HeW, whereas their
      functional connectivity between the thalamus and hypothalamus (important nodes
      for sexual behavior) was stronger. In addition to these singular features, HoM
      displayed 'female' characteristics, with a similar Cth in the left superior
      parietal and cuneus cortices as HeW, but different from HeM. These data suggest
      both singular and sex atypical features and motivate further investigations of
      cerebral midline structures in relation to male homosexuality.

PMID- 30278049
TI  - Elimination testing with adapted scoring reduces guessing and anxiety in multiple
      choice assessments, but does not increase grade average in comparison with
      negative marking.
AB  - BACKGROUND AND HYPOTHESES: This study is the first to offer an in-depth
      comparison of elimination testing with the scoring rule of Arnold & Arnold
      (hereafter referred to as elimination testing with adapted scoring) and negative
      marking. As such, this study is motivated by the search for an alternative for
      negative marking that still discourages guessing, but is less disadvantageous for
      non-relevant student characteristics such a risk-aversion and does not result in
      grade inflation. The comparison is structured around seven hypotheses: in
      comparison with negative marking, elimination testing with adapted scoring leads
      to (1) a similar average score (no grade inflation); (2) students expressing
      their partial knowledge; (3) a decrease in the number of blank answers; (4) no
      gender bias in the number of blank answers; (5) a reduction in guessing; (6) a
      decrease in self-reported test anxiety; and finally (7) students preferring
      elimination testing with adapted scoring over negative marking. METHODOLOGY: To
      investigate the above hypotheses, this study implemented elimination testing with
      adapted scoring and negative marking in real exam settings in two courses in a
      Faculty of Medicine at a large university. Due to changes in the master of
      medicine the same two courses were taught to both students of the 1st and 2nd
      master in the same semester. Given that both student groups could take the same
      exam with different test instructions and scoring methods, a unique opportunity
      occurred in which elimination testing with adapted scoring and negative marking
      could be compared in a high-stakes testing situation. After receiving the grades
      on the exams, students received a questionnaire to assess their experiences.
      FINDINGS: The statistical analysis taking into account student ability and gender
      showed that elimination testing with adapted scoring is a valuable alternative
      for negative marking when looking for a scoring method that discourages guessing.
      In contrast to traditional scoring of elimination testing, elimination testing
      with adapted scoring does not result in grade inflation in comparison with
      negative marking. This study showed that elimination testing with adapted scoring
      reduces blank answers and finds strong indications for the reduction of guessing
      in comparison with negative marking. Finally, students preferred elimination
      testing with adapted scoring over negative marking and reported lower stress
      levels in elimination testing with adapted scoring in comparison with negative
      marking.

PMID- 30278048
TI  - Bioinformatic characterisation of the effector repertoire of the strawberry
      pathogen Phytophthora cactorum.
AB  - The oomycete pathogen Phytophthora cactorum causes crown rot, a major disease of
      cultivated strawberry. We report the draft genome of P. cactorum isolate 10300,
      isolated from symptomatic Fragaria x ananassa tissue. Our analysis revealed that
      there are a large number of genes encoding putative secreted effectors in the
      genome, including nearly 200 RxLR domain containing effectors, 77 Crinklers (CRN)
      grouped into 38 families, and numerous apoplastic effectors, such as phytotoxins
      (PcF proteins) and necrosis inducing proteins. As in other Phytophthora species,
      the genomic environment of many RxLR and CRN genes differed from core eukaryotic
      genes, a hallmark of the two-speed genome. We found genes homologous to known
      Phytophthora infestans avirulence genes including Avr1, Avr3b, Avr4, Avrblb1 and
      AvrSmira2 indicating effector sequence conservation between Phytophthora species
      of clade 1a and clade 1c. The reported P. cactorum genome sequence and associated
      annotations represent a comprehensive resource for avirulence gene discovery in
      other Phytophthora species from clade 1 and, will facilitate effector informed
      breeding strategies in other crops.

PMID- 30278050
TI  - Prediction of prkC-mediated protein serine/threonine phosphorylation sites for
      bacteria.
AB  - As an abundant post-translational modification, reversible phosphorylation is
      critical for the dynamic regulation of various biological processes. prkC, a
      critical serine/threonine-protein kinase in bacteria, plays important roles in
      regulation of signaling transduction. Identification of prkC-specific
      phosphorylation sites is fundamental for understanding the molecular mechanism of
      phosphorylation-mediated signaling. However, experimental identification of
      substrates for prkC is time-consuming and labor-intensive, and computational
      methods for kinase-specific phosphorylation prediction in bacteria have yet to be
      developed. In this study, we manually curated the experimentally identified
      substrates and phosphorylation sites of prkC from the published literature. The
      analyses of the sequence preferences showed that the substrate recognition
      pattern for prkC might be miscellaneous, and a complex strategy should be
      employed to predict potential prkC-specific phosphorylation sites. To develop the
      predictor, the amino acid location feature extraction method and the support
      vector machine algorithm were employed, and the methods achieved promising
      performance. Through 10-fold cross validation, the predictor reached a
      sensitivity of 91.67% at the specificity of 95.12%. Then, we developed freely
      accessible software, which is provided at http://free.cancerbio.info/prkc/. Based
      on the predictor, hundreds of potential prkC-specific phosphorylation sites were
      annotated based on the known bacterial phosphorylation sites. prkC-PSP was the
      first predictor for prkC-specific phosphorylation sites, and its prediction
      performance was promising. We anticipated that these analyses and the predictor
      could be helpful for further studies of prkC-mediated phosphorylation.

PMID- 30278051
TI  - Enhanced neutralizing antibody response induced by inactivated enterovirus 71 in
      cynomolgus monkeys.
AB  - Enterovirus 71 (EV71) is a major etiological agent of various public health
      issues, particularly in the Asia-Pacific region. EV71 causes hand-foot-and-mouth
      disease (HFMD) and is associated with serious neurological disorders in young
      children. A formalin-inactivated EV71 candidate vaccine (KCDC-HFMDV1-EV71) based
      on the C4 subgenotype was previously developed and confirmed to be a potential
      candidate vaccine for prevention of EV71 infection in mice. In this study, an
      inactivated EV71 vaccine was used for analysis of long-term immunogenicity and
      efficacy in cynomolgus monkeys, a common nonhuman primate model. The vaccine was
      immunized three times at 0, 4, and 8 weeks with either 20-MUg doses of EV71
      candidate vaccine formulated with aluminum hydroxide gel adjuvant or phosphate
      buffered saline as a control. The group immunized with the inactivated EV71
      showed significantly increased EV71-specific antibody and serum neutralizing
      antibody titers at 3 weeks after vaccination and maintained these elevated titers
      until the end of the experiment (54 weeks after vaccination). The sera from
      vaccinated cynomolgus monkeys showed a crossreactive neutralizing antibody
      response to the heterologous subtype of EV71 (B1-4, C1, and C2). These findings
      suggest that the inactivated EV71 candidate vaccine may be a potential vaccine
      candidate and valuable tool for the control of HFMD.

PMID- 30278052
TI  - A Holocene landscape dynamic multiproxy reconstruction: How do interactions
      between fire and insect outbreaks shape an ecosystem over long time scales?
AB  - At a multi-millennial scale, various disturbances shape boreal forest stand
      mosaics and the distribution of species. Despite the importance of such
      disturbances, there is a lack of studies focused on the long-term dynamics of
      spruce budworm (Choristoneura fumiferana (Clem.)) (SBW) outbreaks and the
      interaction of insect outbreaks and fire. Here, we combine macrocharcoal and
      plant macrofossils with a new proxy-lepidopteran scales-to describe the Holocene
      ecology around a boreal lake. Lepidopteran scales turned out to be a more robust
      proxy of insect outbreaks than the traditional proxies such as cephalic head
      capsules and feces. We identified 87 significant peaks in scale abundance over
      the last 10 000 years. These results indicate that SBW outbreaks were more
      frequent over the Holocene than suggested by previous studies. Charcoal
      accumulation rates match the established fire history in eastern Canada: a more
      fire-prone early and late Holocene and reduced fire frequency during the mid
      Holocene. Although on occasion, both fire and insect outbreaks were coeval, our
      results show a generally inverse relationship between fire frequency and insect
      outbreaks over the Holocene.

PMID- 30278053
TI  - Cost-effectiveness of financial incentives and disincentives for improving food
      purchases and health through the US Supplemental Nutrition Assistance Program
      (SNAP): A microsimulation study.
AB  - BACKGROUND: The Supplemental Nutrition Assistance Program (SNAP) provides
      approximately US$70 billion annually to support food purchases by low-income
      households, supporting approximately 1 in 7 Americans. In the 2018 Farm Bill,
      potential SNAP revisions to improve diets and health could include financial
      incentives, disincentives, or restrictions for certain foods. However, the
      overall and comparative impacts on health outcomes and costs are not established.
      We aimed to estimate the health impact, program and healthcare costs, and cost
      effectiveness of food incentives, disincentives, or restrictions in SNAP. METHODS
      AND FINDINGS: We used a validated microsimulation model (CVD-PREDICT), populated
      with national data on adult SNAP participants from the National Health and
      Nutrition Examination Survey (NHANES) 2009-2014, policy effects from SNAP pilots
      and food pricing meta-analyses, diet-disease effects from meta-analyses, and
      policy, food, and healthcare costs from published literature to estimate the
      overall and comparative impacts of 3 dietary policy interventions: (1) a 30%
      incentive for fruits and vegetables (F&V), (2) a 30% F&V incentive with a
      restriction of sugar-sweetened beverages (SSBs), and (3) a broader
      incentive/disincentive program for multiple foods that also preserves choice
      (SNAP-plus), combining 30% incentives for F&V, nuts, whole grains, fish, and
      plant-based oils and 30% disincentives for SSBs, junk food, and processed meats.
      Among approximately 14.5 million adults on SNAP at baseline with mean age 52
      years, our simulation estimates that the F&V incentive over 5 years would prevent
      38,782 cardiovascular disease (CVD) events, gain 18,928 quality-adjusted life
      years (QALYs), and save $1.21 billion in healthcare costs. Adding SSB restriction
      increased gains to 93,933 CVD events prevented, 45,864 QALYs gained, and $4.33
      billion saved. For SNAP-plus, corresponding gains were 116,875 CVD events
      prevented, 56,056 QALYs gained, and $5.28 billion saved. Over a lifetime, the F&V
      incentive would prevent approximately 303,900 CVD events, gain 649,000 QALYs, and
      save $6.77 billion in healthcare costs. Adding SSB restriction increased gains to
      approximately 797,900 CVD events prevented, 2.11 million QALYs gained, and $39.16
      billion in healthcare costs saved. For SNAP-plus, corresponding gains were
      approximately 940,000 CVD events prevented, 2.47 million QALYs gained, and $41.93
      billion saved. From a societal perspective (including programmatic costs but
      excluding food subsidy costs as an intra-societal transfer), all 3 scenarios were
      cost-saving. From a government affordability perspective (i.e., incorporating
      food subsidy costs, including for children and young adults for whom no health
      gains were modeled), the F&V incentive was of low cost-effectiveness at 5 years
      (incremental cost-effectiveness ratio: $548,053/QALY) but achieved cost
      effectiveness ($66,525/QALY) over a lifetime. Adding SSB restriction, the
      intervention was cost-effective at 10 years ($68,857/QALY) and very cost
      effective at 20 years ($26,435/QALY) and over a lifetime ($5,216/QALY). The
      combined incentive/disincentive program produced the largest health gains and
      reduced both healthcare and food costs, with net cost-savings of $10.16 billion
      at 5 years and $63.33 billion over a lifetime. Results were consistent in
      probabilistic sensitivity analyses: for example, from a societal perspective,
      1,000 of 1,000 iterations (100%) were cost-saving for all 3 interventions. Due to
      the nature of simulation studies, the findings cannot prove the health and cost
      impacts of national SNAP interventions. CONCLUSIONS: Leveraging healthier eating
      through SNAP could generate substantial health benefits and be cost-effective or
      cost-saving. A combined food incentive/disincentive program appears most
      effective and may be most attractive to policy-makers.

PMID- 30278054
TI  - Leprosy in children under 15 years of age in Brazil: A systematic review of the
      literature.
AB  - BACKGROUND: Leprosy is a chronic infectious disease neglected, caused by
      Mycobacterium leprae, considered a public health problem because may cause
      permanent physical disabilities and deformities, leading to severe limitations.
      This review presents an overview of the results of epidemiological studies on
      leprosy occurrence in childhood in Brazil, aiming to alert health planners and
      managers to the actual need to institute special control strategies.
      METHODOLOGY/PRINCIPAL FINDINGS: Data collection consisted of an electronic search
      for publications in eight databases: Literatura Latino-Americana e do Caribe em
      Ciencias da Saude (LILACS), Scientific Electronic Library Online (SciELO),
      PuBMed, Biblioteca Virtual em Saude (BVS), SciVerse Scopus (Scopus), CAPES theses
      database, CAPES journals database and Web of Science of papers published up to
      2016. After apply selection criteria, twenty-two papers of studies conducted in
      four different regions of Brazil and published between 2001 and 2016 were
      included in the review. The leprosy detection rate ranged from 10.9 to 78.4 per
      100,000 inhabitants. Despite affecting both sexes, leprosy was more common in
      boys and in 10-14-year-olds. Although the authors reported a high cure proportion
      (82-90%), between 1.7% and 5.5% of the individuals developed a disability
      resulting from the disease. CONCLUSIONS/SIGNIFICANCE: The findings of this review
      shows that leprosy situation in Brazilian children under 15 years is extremely
      adverse in that the leprosy detection rate remains high in the majority of
      studies. The proportion of cases involving disability is also high and reflects
      the difficulties and the poor effectiveness of actions aimed at controlling the
      disease. The authors suggest the development of studies in spatial clusters of
      leprosy, where beyond the routine actions established, are included news
      strategies of active search and campaigns and actions of educations inside the
      clusters of this disease. The new agenda needs to involve the precepts of
      ethical, humane and supportive care, in order to achieve a new level of leprosy
      control in Brazil.

PMID- 30278055
TI  - Duplex Proximity Sequencing (Pro-Seq): A method to improve DNA sequencing
      accuracy without the cost of molecular barcoding redundancy.
AB  - A challenge in the clinical adoption of cell-free DNA (cfDNA) liquid biopsies for
      cancer care is their high cost compared to potential reimbursement. The most
      common approach used in liquid biopsies to achieve high specificity detection of
      circulating tumor DNA (ctDNA) among a large background of normal cfDNA is to
      attach molecular barcodes to each DNA template, amplify it, and then sequence it
      many times to reach a low-error consensus. In applications where the highest
      possible specificity is required, error rate can be lowered further by
      independently detecting the sequences of both strands of the starting cfDNA.
      While effective in error reduction, the additional sequencing redundancy required
      by such barcoding methods can increase the cost of sequencing up to 100-fold over
      standard next-generation sequencing (NGS) of equivalent depth. We present a novel
      library construction and analysis method for NGS that achieves comparable
      performance to the best barcoding methods, but without the increase in sequencing
      and subsequent sequencing cost. Named Proximity-Sequencing (Pro-Seq), the method
      merges multiple copies of each template into a single sequencing read by
      physically linking the molecular copies so they seed a single sequencing cluster.
      Since multiple DNA copies of the same template are compared for consensus within
      the same cluster, sequencing accuracy is improved without the use of redundant
      reads. Additionally, it is possible to represent both senses of the starting
      duplex in a single cluster. The resulting workflow is simple, and can be
      completed by a single technician in a work day with minimal hands on time. Using
      both cfDNA and cell line DNA, we report the average per-mutation detection
      threshold and per-base analytical specificity to be 0.003% and >99.9997%
      respectively, demonstrating that Pro-Seq is among the highest performing liquid
      biopsy technologies in terms of both sensitivity and specificity, but with
      greatly reduced sequencing costs compared to existing methods of comparable
      accuracy.

PMID- 30278056
TI  - Tutorial for using SliceOmatic to calculate thigh area and composition from
      computed tomography images from older adults.
AB  - OBJECTIVE: Area of muscle, fat, and bone is often measured in thigh CT scans when
      tissue composition is a key outcome. SliceOmatic software is commonly referenced
      for such analysis but published methods may be insufficient for new users. Thus,
      a quick start guide to calculating thigh composition using SliceOmatic has been
      developed. METHODS: CT images of the thigh were collected from older (69 +/- 4
      yrs, N = 24) adults before and after 12-weeks of resistance training. SliceOmatic
      was used to segment images into seven density regions encompassing fat, muscle,
      and bone from -190 to +2000 Hounsfield Units [HU]. The relative contributions to
      thigh area and the effects of tissue density overlap for skin and marrow with
      muscle and fat were determined. RESULTS: The largest contributors to the thigh
      were normal fat (-190 to -30 HU, 29.1 +/- 7.4%) and muscle (35 to 100 HU, 48.9 +/
      8.2%) while the smallest were high density (101 to 150 HU, 0.79 +/- 0.50%) and
      very high density muscle (151 to 200 HU, 0.07 +/- 0.02%). Training significantly
      (P<0.05) increased area for muscle in the very low (-29 to -1 HU, 5.5 +/- 7.9%),
      low (0 to 34 HU, 9.6 +/- 16.8%), normal (35 to 100 HU, 4.2 +/- 7.9%), and high
      (100 to 150 HU, 70.9 +/- 80.6%) density ranges for muscle. Normal fat, very high
      density muscle and bone did not change (P>0.05). Contributions to area were
      altered by ~1% or less and the results of training were not affected by
      accounting for skin and marrow. CONCLUSIONS: When using SliceOmatic to calculate
      thigh composition, accounting for skin and marrow may not be necessary. We
      recommend defining muscle as -29 to +200 HU but that smaller ranges (e.g. low
      density muscle, 0 to 34 HU) can easily be examined for relationships with the
      health condition and intervention of interest. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT02261961.

PMID- 30278057
TI  - Cataract significantly influences quantitative measurements on swept-source
      optical coherence tomography angiography imaging.
AB  - PURPOSE: To analyze retinal blood flow before and after cataract surgery using
      swept-source optical coherence tomography angiography (SS-OCTA). METHODS:
      Prospective observational study. Consecutive patients were recruited and scanned
      using SS-OCTA before and after cataract surgery. Laser flare photometry were
      performed post-surgery. Perfusion and vessel density of superficial (SCP) and
      deep capillary plexuses (DCP) of the 3 * 3 mm images as well as foveal avascular
      zone (FAZ) measurements were assessed. Vessel continuity, vessel visibility and
      presence of artefacts were evaluated by two blinded graders using a predefined
      grading protocol. RESULTS: Thirteen eyes of 12 patients met the inclusion
      criteria. There was a significant increase of perfusion and vessel densities in
      both the SCP and the DCP after cataract surgery within the 3 * 3 mm images.
      Significantly better distinguishability of FAZ border was observed
      postoperatively in both SCP and DCP, however, FAZ area and perimeter measurements
      did not significantly change after cataract surgery. Mean number of motion
      artifacts in SCP and DCP numerically decreased by 37% (P = .089) and 42% (P =
      .080). CONCLUSIONS: Lens opacities have a significant influence on retinal blood
      flow measurements in SS-OCTA and should be considered in quantitative vessel
      analysis. Inflammation may also impact the assessment of density parameters. FAZ
      measurements seems to be the most robust parameters in terms of media opacity.

PMID- 30278058
TI  - A multicenter comparison of quantification methods for antisense oligonucleotide
      induced DMD exon 51 skipping in Duchenne muscular dystrophy cell cultures.
AB  - BACKGROUND: Duchenne muscular dystrophy is a lethal disease caused by lack of
      dystrophin. Skipping of exons adjacent to out-of-frame deletions has proven to
      restore dystrophin expression in Duchenne patients. Exon 51 has been the most
      studied target in both preclinical and clinical settings and the availability of
      standardized procedures to quantify exon skipping would be advantageous for the
      evaluation of preclinical and clinical data. OBJECTIVE: To compare methods
      currently used to quantify antisense oligonucleotide-induced exon 51 skipping in
      the DMD transcript and to provide guidance about the method to use. METHODS: Six
      laboratories shared blinded RNA samples from Duchenne patient-derived muscle
      cells treated with different amounts of exon 51 targeting antisense
      oligonucleotide. Exon 51 skipping levels were quantified using five different
      techniques: digital droplet PCR, single PCR assessed with Agilent bioanalyzer,
      nested PCR with agarose gel image analysis by either ImageJ or GeneTools software
      and quantitative real-time PCR. RESULTS: Differences in mean exon skipping levels
      and dispersion around the mean were observed across the different techniques.
      Results obtained by digital droplet PCR were reproducible and showed the smallest
      dispersion. Exon skipping quantification with the other methods showed
      overestimation of exon skipping or high data variation. CONCLUSIONS: Our results
      suggest that digital droplet PCR was the most precise and quantitative method.
      The quantification of exon 51 skipping by Agilent bioanalyzer after a single
      round of PCR was the second-best choice with a 2.3-fold overestimation of exon 51
      skipping levels compared to digital droplet PCR.

PMID- 30278059
TI  - Variation sites at the HLA-G 3' untranslated region confer differential
      susceptibility to HIV/HPV co-infection and aneuploidy in cervical cell.
AB  - Post-transcriptional regulatory elements associated with transcript degradation
      or transcript instability have been described at the 3' untranslated region
      (3'UTR) of the HLA-G gene. Considering that HPV infection and aneuploidy, which
      causes gene instability, are associated with cervical cell malignancy, as well as
      the fact that HIV infection and HLA-G may modulate the immune response, the
      present study aimed to compare the frequencies of HLA-G 3'UTR polymorphic sites
      (14-base pair insertion/deletion, +3142C/G, and +3187A/G) between 226 HIV+ women
      co-infected (n = 82) or not with HPV (n = 144) and 138 healthy women. We also
      evaluated the relationship between those HLA-G 3'UTR variants and aneuploidy in
      cervical cells. HPV types and HLA-G polymorphisms were determined by PCR and
      sequencing of cervical samples DNA. Aneuploidy in cervical cell was measured by
      flow cytometry. The HLA-G 3'UTR 14-bp ins/del was not associated with either HIV
      nor HIV/HPV co-infection. The +3142G allele (p = 0.049) and +3142GG genotype (p =
      0.047) were overrepresented in all HIV-infected women. On the other hand, the
      +3187G allele (p = 0.028) and the +3187GG genotype (p = 0.026) predominated among
      healthy women. The +3142G (p = 0.023) and +3187A (p = 0.003) alleles were
      associated with predisposition to HIV infection, irrespective of the presence or
      not of HIV/HPV co-infection. The diplotype formed by the combination of the
      +3142CX (CC or CG) and +3187AA genotype conferred the highest risk for aneuploidy
      in cervical cell induced by HPV. The HLA-G 3'UTR +3142 and +3187 variants
      conferred distinct susceptibility to HIV infection and aneuploidy.

PMID- 30278060
TI  - Helps from flipped classroom in learning suturing skill: The medical students'
      perspective.
AB  - BACKGROUND: Today, flipped classroom (FC) has been widely used in medical
      education. However, the effectiveness of FC remains controversial. The variation
      may cause by different subjects or different course design. Moreover, those
      studies did not explain how the association among different domains of learning
      objective was in FCs. The purpose of this study was to explore the help of
      learning domains from a FC of suturing skill in year-5 medical students. DESIGN:
      This study determined sample size according to statistical power. A minimum
      number of 77 participants for regression analysis are needed. Therefore, this
      study enrolled 78 medical students in a 2-hour suturing course, which consisted
      of pre-class video and in-class instruction. Both simple and mattress suturing
      were taught. The students received an anonymous survey with questionnaire of Help
      from Instruction Questionnaire for Clinical Skills (HIQ-CS) after the course. The
      HIQ-CS was developed by medical education team according to Bloom's taxonomy, and
      its reliability was favorable (Cronbach's ^l = 0.839). Factor loadings among all
      items in the HIQ-CS was also favorable (0.790 to 0.849). This study determined
      consensus of students' perspective by median (Me) and interquartile range (IQR),
      and tested mediation among different learning domains by regression. RESULTS: The
      results showed medical students agreed FC can help them in learning suturing (Me
      = 4, IQR = 1). The cognitive help (beta = .526, p < .001) was completely mediated
      by psychomotor help (beta = .399, p < .001) and affective help (beta = .413, p <
      .001) to overall helps in FC. The affective help (beta = .617, p < .001) was
      partially mediated by psychomotor help to overall helps in FC. CONCLUSIONS: FC
      may help students in learning suturing skill in different domains. Our model
      explains the cognitive help from FC provides an important foundation for the
      helps of other domains. Although the model should be examined by different
      curricula and measurements in future, the model of help from instruction in our
      study provided an innovated concept and framework in medical education.

PMID- 30278062
TI  - Correction: Landscape drivers of recent fire activity (2001-2017) in south
      central Chile.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0201195.].

PMID- 30278061
TI  - The relationship between anogenital HPV types and incident HIV infection among
      men who have sex with men and transgender women in Lima, Peru: Findings from a
      prospective cohort study.
AB  - Although it is known that individuals living with HIV have a higher HPV
      prevalence, the impact of individual HPV types on HIV acquisition is less clear.
      In this prospective cohort study we investigated the relationship between HPV
      types and incident HIV infection among men who have sex with men (MSM) and
      transgender women (TW) in Lima, Peru. Six hundred HIV-negative Peruvian MSM and
      TW participated in a 2-year study with biannual visits. At baseline, participants
      completed a computerized, self-administered questionnaire on sexual behavior and
      HPV knowledge and underwent a physical exam including anogenital swabs for HPV
      DNA (37 genotypes via linear array testing) and HIV testing; follow-up visits
      included the questionnaire and HIV testing. Participant mean age was 25 years
      (range = 18-40), with 48.9% self-identifying as gay and 86.5% reporting having
      sex exclusively with men. At baseline, 530 participants had HPV DNA present
      (61.1% with high-risk HPV, 84.9% with low-risk HPV). Among 571 participants who
      returned for any study visit, 73 (12.8%) became infected with HIV during the 2
      year follow-up (6% HIV incidence). Compared to those without HIV, more
      participants with HIV had any HPV type present (97.3% vs. 87.6%, respectively, p
      = .01), more than one HPV type (79.5% vs. 58.2%, p < .01), or high-risk HPV
      (72.6% vs. 51.4%, p < .01). Some participants lost to follow-up could have been
      HIV-positive, which would have affected the relationship of HPV and HIV
      infection. Our prospective study showed that participants with any HPV type, more
      than one HPV type, or high-risk HPV were more likely to test positive for HIV.
      Although most studies have shown HPV-HIV coinfection, our findings illustrate the
      strong relationship between individual HPV types and HIV infection. This further
      illustrates the potential utility of HPV vaccine for MSM and TW, not only for HPV
      prevention but also possibly for HIV prevention.

PMID- 30278063
TI  - Optimal clustering under uncertainty.
AB  - Classical clustering algorithms typically either lack an underlying probability
      framework to make them predictive or focus on parameter estimation rather than
      defining and minimizing a notion of error. Recent work addresses these issues by
      developing a probabilistic framework based on the theory of random labeled point
      processes and characterizing a Bayes clusterer that minimizes the number of
      misclustered points. The Bayes clusterer is analogous to the Bayes classifier.
      Whereas determining a Bayes classifier requires full knowledge of the feature
      label distribution, deriving a Bayes clusterer requires full knowledge of the
      point process. When uncertain of the point process, one would like to find a
      robust clusterer that is optimal over the uncertainty, just as one may find
      optimal robust classifiers with uncertain feature-label distributions. Herein, we
      derive an optimal robust clusterer by first finding an effective random point
      process that incorporates all randomness within its own probabilistic structure
      and from which a Bayes clusterer can be derived that provides an optimal robust
      clusterer relative to the uncertainty. This is analogous to the use of effective
      class-conditional distributions in robust classification. After evaluating the
      performance of robust clusterers in synthetic mixtures of Gaussians models, we
      apply the framework to granular imaging, where we make use of the asymptotic
      granulometric moment theory for granular images to relate robust clustering
      theory to the application.

PMID- 30278064
TI  - Screening tool to identify adolescents living with HIV in a community setting in
      Zimbabwe: A validation study.
AB  - INTRODUCTION: A simple cost-effective strategy to pre-screen for targeted HIV
      testing can have substantial benefit in high burden and resource limited
      settings. A 4-item (previous hospitalisation, orphanhood, poor health status, and
      recurring skin problems) screening tool to identify adolescents living with HIV
      has previously shown high sensitivity in healthcare facility settings. We
      validated this screening tool in a community setting, in Harare, Zimbabwe in a
      community-based HIV prevalence survey. METHODS: A community-based HIV prevalence
      survey was conducted among individuals aged 8-17 years with guardian consent and
      child assent and residing in 7 communities during the period February 2015 to
      December 2015. Participants without previously diagnosed HIV were evaluated for
      the probability of having HIV using the screening tool. HIV status was defined
      using an anonymous HIV test which was done using Oral Mucosal Transudate (OMT). A
      questionnaire was also administered to ascertain self-reported HIV status and
      screening tool items. The validity of a 4-item screening tool was tested.
      Sensitivity and specificity of the screening tool was assessed against the HIV
      status based on OMT result. RESULTS: Prevalence survey participants were 5386
      children who had an HIV test result, aged 8-17 years. However, 5384, who did not
      report testing HIV positive and responded to all screening tool item questions
      were included in the validation. Their median age was 12 (IQR: 10-15) years, 2515
      (46.7%) were male. HIV prevalence was 1.3% (95% CI:1.0-1.8%). The 4-item
      screening tool had poor accuracy with an area under the receiver operating curve
      of 0.65(95% CI: 0.60-0.72) at a cut-off score>=1. Its sensitivity was 56.3% (95%
      CI:44.0-68.1%) and specificity of 75.1% (95% CI:73.9-76.3%), PPV of 2.9% (95%
      CI:2.1-3.9%) and a NPV of 99.2% (95% CI:98.9-99.5%). The number needed to test to
      diagnose one child using the screening tool was 55% lower than universal testing
      for HIV. CONCLUSION: Use of the 4-item screening tool could be a strategy that
      can be adopted to identify children living with HIV in a community setting in
      resource limited settings by reducing the number needed to test compared to
      universal testing since it is inexpensive, easy to administer and not harmful.
      However, screening items adapted to a community setting need to be explored to
      improve the performance of the screening tool.

PMID- 30278065
TI  - Intragenus (Homo) variation in a chemokine receptor gene (CCR5).
AB  - Humans have a comparatively higher rate of more polymorphisms in regulatory
      regions of the primate CCR5 gene, an immune system gene with both general and
      specific functions. This has been interpreted as allowing flexibility and
      diversity of gene expression in response to varying disease loads. A broad
      expression repertoire is useful to humans-the only globally distributed primate
      due to our unique adaptive pattern that increased pathogen exposure and disease
      loads (e.g., sedentism, subsistence practices). The main objective of the study
      was to determine if the previously observed human pattern of increased variation
      extended to other members of our genus, Homo. The data for this study are mined
      from the published genomes of extinct hominins (four Neandertals and two
      Denisovans), an ancient human (Ust'-Ishim), and modern humans (1000 Genomes). An
      average of 15 polymorphisms per individual were found in human populations (with
      a total of 262 polymorphisms). There were 94 polymorphisms identified across
      extinct Homo (an average of 13 per individual) with 41 previously observed in
      modern humans and 53 novel polymorphisms (32 in Denisova and 21 in Neandertal).
      Neither the frequency nor distribution of polymorphisms across gene regions
      exhibit significant differences within the genus Homo. Thus, humans are not
      unique with regards to the increased frequency of regulatory polymorphisms and
      the evolution of variation patterns across CCR5 gene appears to have originated
      within the genus. A broader evolutionary perspective on regulatory flexibility
      may be that it provided an advantage during the transition to confrontational
      foraging (and later hunting) that altered human-environment interaction as well
      as during migration to Eurasia and encounters with novel pathogens.

PMID- 30278066
TI  - Associations between mother-preschooler attachment and maternal depression
      symptoms: A systematic review and meta-analysis.
AB  - The current study aimed to systematically review and meta-analyze concurrent and
      longitudinal associations between maternal depression symptoms and mother-child
      attachment during the preschool period (aged 2 to 7 years) as assessed using the
      coding systems by Cassidy and Marvin (1992) and Main and Cassidy (1988). The
      review was pre-registered with PROSPERO (International Prospective Register of
      Systematic Reviews; Registration number CRD42017073417) and was conducted in
      accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta
      Analyses) guidelines. A total of 7,969 records were screened and 18 articles were
      deemed as eligible for inclusion in the review. Studies were reviewed using
      qualitative synthesis techniques and, where appropriate, meta-analysis.
      Qualitative synthesis indicated that mothers of disorganized/controlling children
      most consistently reported the highest levels of depressive symptoms, both
      concurrently and longitudinally. The association between disorganized/controlling
      child attachment and concurrent maternal depressive symptoms was significant (n =
      1,787; g = 0.27, 95% CI [0.13,0.40]), and was not moderated by sample type, child
      gender, or risk of bias. Findings of a relationship between child attachment
      insecurity and maternal depressive symptoms must be qualified due to significant
      within-study heterogeneity and publication bias. Results suggest that maternal
      depressive symptoms may confer risk for disorganized/controlling attachment
      during the preschool period.

PMID- 30278067
TI  - Is topical or intravenous tranexamic acid preferred in total hip arthroplasty? A
      randomized, controlled, noninferiority clinical trial.
AB  - PURPOSE: The present study aimed to confirm the efficacy and safety of topical
      and intravenous tranexamic acid (TXA) compared with that of topical placebo and
      to assess the noninferiority between the two application methods of TXA in
      patients undergoing unilateral primary total hip arthroplasty. METHODS: Our
      randomized controlled trial investigated 170 patients with 1:1:1 allocation to
      two doses of 10-mg/kg intravenous TXA, 3-g topical TXA, and topical placebo of 60
      ml physiological saline groups. The primary outcome, total blood loss, was
      calculated with Nadler and Gross formula. The secondary outcomes included
      allogeneic blood transfusion requirement, drain blood loss, decreased hemoglobin
      level. Noninferiority would be established when the upper limit 95% CI is lower
      than 250 ml of the noninferiority margin for the mean difference of total blood
      loss between topical and intravenous TXA. Thromboembolic complication incidence
      was considered as a safety outcome. RESULTS: The total blood loss of patients
      administered intravenous (mean+/-standard deviation, 1125+/-514 ml) and topical
      TXA (1211+/-425 ml) was significantly reduced compared with that of those
      administered topical placebo (1464+/-556 ml) (p = 0.0012). Drain blood loss and
      hemoglobin level reduction in patients administered with TXA were also
      significantly lower than those in patients administered topical placebo. The mean
      difference of total blood loss between topical and intravenous TXA is 86 ml (95%
      CI, -88 to 260 ml). The complications were comparable between patients managed
      with TXA and patients with topical placebo. CONCLUSION: The noninferiority of
      topical TXA to intravenous TXA can not be concluded. Considering no significant
      difference was found in all efficacy outcomes between the two administration
      methods. Any of the two TXA administration methods can be adopted for blood loss
      prevention in total hip arthroplasty.

PMID- 30278068
TI  - Visualization of the auditory pathway in rats with 18F-FDG PET activation studies
      based on different auditory stimuli and reference conditions including cochlea
      ablation.
AB  - Activation studies with positron emission tomography (PET) in auditory implant
      users explained some of the mechanisms underlying the variability of achieved
      speech comprehension. Since future developments of auditory implants will include
      studies in rodents, we aimed to inversely translate functional PET imaging to
      rats. In normal hearing rats, activity in auditory and non-auditory regions was
      studied using 18F-fluorodeoxyglucose (18F-FDG) PET with 3 different acoustic
      conditions: sound attenuated laboratory background, continuous white noise and
      rippled noise. Additionally, bilateral cochlea ablated animals were scanned. 3D
      image data were transferred into a stereotaxic standard space and evaluated using
      volume of interest (VOI) analyses and statistical parametric mapping (SPM). In
      normal hearing rats alongside the auditory pathway consistent activations of the
      nucleus cochlearis (NC), olivary complex (OC) and inferior colliculus (IC) were
      seen comparing stimuli with background. In this respect, no increased activation
      could be detected in the auditory cortex (AC), which even showed deactivation
      with white noise stimulation. Nevertheless, higher activity in the AC in normal
      hearing rats was observed for all 3 auditory conditions against the cochlea
      ablated status. Vice versa, in ablated status activity in the olfactory nucleus
      (ON) was higher compared to all auditory conditions in normal hearing rats. Our
      results indicate that activations can be demonstrated in normal hearing animals
      based on 18F-FDG PET in nuclei along the central auditory pathway with different
      types of noise stimuli. However, in the AC missing activation with respect to the
      background advises the need for more rigorous background noise attenuation for
      non-invasive reference conditions. Finally, our data suggest cross-modal
      activation of the olfactory system following cochlea ablation-underlining, that
      18F-FDG PET appears to be well suited to study plasticity in rat models for
      cochlear implantation.

PMID- 30278069
TI  - Differential sonographic features of the extensor pollicis longus tendon rupture
      and other finger tendons rupture in the setting of hand and wrist trauma.
AB  - PURPOSE: To investigate the difference between sonographic findings in extensor
      pollicis longus tendons rupture and other finger tendons rupture in patients
      sustaining hand and wrist trauma. METHODS: Twenty-four patients who presented
      with signs and symptoms clinically suspicious for tendon injury and surgically
      confirmed tendon rupture were included in this study. We analyzed 6 sonographic
      features: discontinuity of the tendon, pseudomass formation, decreased
      echogenicity of the tendon, retraction of the ruptured tendon, fluid collection
      within the tendon sheath, and the motion of the tendon. We compared the
      sonographic features of ruptured extensor pollicis longus tendons with the other
      ruptured finger tendons. RESULTS: Discontinuity of the tendon was the most common
      sonographic findings and retraction of the ruptured tendon was the second most
      common findings. Fourteen of 16 cases with a dynamic study on sonography showed
      loss of normal motion of the tendon. Pseudomass formation was the second most
      common feature in ruptured extensor pollicis longus tendons, in contrast to the
      other ruptured finger tendons (p < 0.05). CONCLUSION: Using ultrasonography,
      detection of discontinuity of the tendon, retraction of the ruptured tendon, and
      limitation of tendon motion could be very helpful for diagnosing a tendon rupture
      in hand and wrist trauma. Pseudomass formation could be more specific for
      diagnosing extensor pollicis longus tendon ruptures compared with other finger
      tendons.

PMID- 30278070
TI  - Correction: Intra- and Inter-Task Reliability of Spatial Attention Measures in
      Pseudoneglect.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0138379.].

PMID- 30278071
TI  - Dietary or supplemental fermentable fiber intake reduces the presence of
      Clostridium XI in mouse intestinal microbiota: The importance of higher fecal
      bacterial load and density.
AB  - OBJECTIVES: Clostridium difficile infection is a public health concern. C.
      difficile was found in healthy human intestine as a member of Clostridium XI.
      Because soluble fermentable fiber ingestion affects intestinal microbiota, we
      used fiber-containing diets to determine the intestinal microbial condition that
      could reduce the presence of Clostridium XI. METHODS: Newly weaned male mice were
      assigned to three published diets: Control AIN-93G purified diet with only poorly
      fermented cellulose; Control plus 5% purified fermentable fiber inulin; Chow with
      wheat, soybean and corn that provide a mixture of unpurified dietary fibers.
      Methods were developed to quantify 24-hour fecal microbial load and microbial DNA
      density. The relative abundance of bacterial genera and the bacterial diversity
      were determined through 16S rRNA sequence-based fecal microbiota analysis.
      RESULTS: Mice adjusted food intake to maintain the same energy intake and body
      weight under these three moderate-fat (7% w:w) diets. Chow-feeding led to higher
      food intake but also higher 24-h fecal output. Chow-feeding and 1-8 wk ingestion
      of inulin-supplemented diet increased daily fecal microbial load and density
      along with lowering the prevalence of Clostridium XI to undetectable. Clostridium
      XI remained undetectable until 4 weeks after the termination of inulin
      supplemented diet. Fermentable fiber intake did not consistently increase
      probiotic genera such as Bifidobacterium or Lactobacillus. Chow feeding, but not
      inulin supplementation, increased the bacterial diversity. CONCLUSIONS: Increase
      fecal microbial load/density upon fermentable fiber ingestion is associated with
      a lower and eventually undetectable presence of Clostridium XI. Higher bacterial
      diversity or abundance of particular genera is not apparently essential. Future
      studies are needed to see whether this observation can be translated into the
      reduction of C. difficile at the species level in at-risk populations.

PMID- 30278072
TI  - Quantitative phosphoproteomic analysis identifies novel functional pathways of
      tumor suppressor DLC1 in estrogen receptor positive breast cancer.
AB  - Deleted in Liver Cancer-1 (DLC1), a member of the RhoGAP family of proteins,
      functions as a tumor suppressor in several cancers including breast cancer.
      However, its clinical relevance is unclear in breast cancer. In this study,
      expression of DLC1 was correlated with prognosis using publicly available breast
      cancer gene expression datasets and quantitative Reverse Transcription PCR in
      cohorts of Estrogen Receptor-positive (ER+) breast cancer. Low expression of DLC1
      correlates with poor prognosis in patients with ER+ breast cancer with further
      decrease in metastatic lesions. The Cancer Genome Atlas (TCGA) data showed that
      down regulation of DLC1 is not due to methylation or mutations. To seek further
      insights in understanding the role of DLC1 in ER+ breast cancer, we stably
      overexpressed DLC1-full-length (DLC1-FL) in T-47D breast cancer cells; this
      inhibited cell colony formation significantly in vitro compared to its control
      counterpart. Label-free global proteomic and TiO2 phosphopeptide enrichment
      assays (ProteomeXchange identifier PXD008220) showed that 205 and 122
      phosphopeptides were unique to DLC1-FL cells and T-47D-control cells,
      respectively, whereas 6,726 were quantified by phosphoproteomics analysis in both
      conditions. The top three significant clusters of differentially phosphopeptides
      identified by DAVID pathway analysis represent cell-cell adhesion, mRNA
      processing and splicing, and transcription regulation. Phosphoproteomics analysis
      documented an inverse relation between DLC1 expression and several
      phosphopeptides including epithelial cell transforming sequence 2 (ECT2).
      Decreased phosphorylation of ECT2 at the residue T359, critical for its active
      conformational change, was validated by western blot. In addition, the ECT2 T359
      containing phosphopeptide was detected in both basal and luminal patient-derived
      breast cancers breast cancer phosphoproteomics data on the Clinical Proteomic
      Tumor Analysis Consortium (CPTAC) Assay portal. Together, for the first time,
      this implicates ECT2 phosphorylation in breast cancer, which has been proposed as
      a therapeutic target in lung cancer. In conclusion, this data suggests that low
      expression of DLC1 is associated with poor prognosis. Targeting ECT2
      phosphopeptides could provide a promising mechanism for controlling poor
      prognosis seen in DLC1low ER+ breast cancer.

PMID- 30278073
TI  - Geographical variations and influential factors in prevalence of cardiometabolic
      diseases in South Korea.
AB  - Geographical variations and influential factors of disease prevalence are crucial
      information enabling optimal allocation of limited medical resources and
      prioritization of appropriate treatments for each regional unit. The purpose of
      this study was to explore the geographical variations and influential factors of
      cardiometabolic disease prevalence with respect to 230 administrative districts
      in South Korea. Global Moran's I was calculated to determine whether the
      standardized prevalences of cardiometabolic diseases (hypertension, stroke, and
      diabetes mellitus) were spatially clustered. The CART algorithm was then applied
      to generate decision tree models that could extract the diseases' regional
      influential factors from among 101 demographic, economic, and public health data
      variables. Finally, the accuracies of the resulting model-hypertension (67.4%),
      stroke (62.2%), and diabetes mellitus (56.5%)-were assessed by ten-fold cross
      validation. Marriage rate was the main determinant of geographic variation in
      hypertension and stroke prevalence, which has the possibility that married life
      could have positive effects in lowering disease risks. Additionally, stress
      related variables were extracted as factors positively associated with
      hypertension and stroke. In the opposite way, the wealth status of a region was
      found to have an influence on the prevalences of stroke and diabetes mellitus.
      This study suggested a framework for provision of novel insights into the
      regional characteristics of diseases and the corresponding influential factors.
      The results of the study are anticipated to provide valuable information for
      public health practitioners' cost-effective disease management and to facilitate
      primary intervention and mitigation efforts in response to regional disease
      outbreaks.

PMID- 30278076
TI  - Retraction: Activated K-ras and INK4a/Arf Deficiency Cooperate During the
      Development of Pancreatic Cancer by Activation of Notch and NF-kappaB Signaling
      Pathways.

PMID- 30278074
TI  - Does nutritional status affect Parkinson's Disease features and quality of life?
AB  - OBJECTIVES: The aim of this study was to determine the relationship between
      nutritional status and Parkinson's Disease (PD) features in association with
      depression, anxiety and quality of life in people with PD. MATERIALS AND METHODS:
      This study was conducted on 96 patients with idiopathic PD to whom the following
      scales were applied: Unified Parkinson's Disease Rating Scale (UPDRS), 39-item PD
      questionnaire (PDQ-39), Hospital Anxiety and Depression Score (HADS), Mini
      Nutritional Assessment (MNA). The scales and measurements were applied to
      patients at their first assessment. Patients with malnutrition or at risk of
      malnutrition were assessed by the dietitian and nutrition nurse. These patients
      received nutritional support through personalized diet recommendations and
      appropriate enteral nutritional products, considering factors such as age,
      comorbidity, socioeconomic and cultural conditions. At the end of 6 weeks, the
      scales and measurements applied during the first visit were again applied to the
      patients. RESULTS: A significant and inverse correlation was determined between
      mental (Spearman r:-0.510, p<0.001), activities of daily living (Spearman r:
      0.520, p<0.001), motor (Spearman r:-0.480, p<0.001), complications (Spearman r:
      0.346, p<0.001) UPDRS subdivisions and total scores (Spearman r:-0.644, p<0.001)
      and total MNA score. A significant and inverse correlation was found between all
      PDQ-39 subdomains and total MNA score (p<0.05). The highest inverse correlations
      were found in mobility (Spearman r:-0.690, p<0.001) and stigma (Spearman r:
      0.570, p<0.001). Both depression (Spearman r:-0.631, p<0.001) and anxiety
      (Spearman r:-0.333, p<0.001) scores were determined to be inversely correlated
      with total MNA score. At the 6-week control visit, significantly lower scores
      were found in all subdivisions and in the total UPDRS score, PDQ-39 score and in
      the patients' anxiety and depression scores (p<0.05). MNA scores were found to be
      significantly higher in the assessment performed after 6 weeks of support for
      patients who had abnormal nutritional status at inception (p<0.001). CONCLUSION:
      PD motor and nonmotor functions, disease duration and severity are related to
      nutritional status. Quality of life was also shown to be affected by changes in
      the nutritional status. These results show that nutritional status assessment
      should be a standard approach in the PD treatment and follow-up processes.

PMID- 30278075
TI  - Cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected
      with hepatitis E virus: The bone marrow as a possible new viral target.
AB  - Hepatitis E virus (HEV) transmission through infected blood and blood products
      has already been described. However, little is known about the bone marrow (BM)
      as source of HEV infection. Our study aimed to investigate the presence of HEV
      antigen (Ag) and histological changes in BM of cynomolgus monkeys (Macaca
      fascicularis) experimentally and naturally infected with HEV. Four cynomolgus
      monkeys with acute, and two with chronic hepatitis E ? after immunosuppressive
      therapy with tacrolimus ? were compared with one colony-bred animal naturally
      infected. Both, natural and experimental infections were characterized by anti
      HEV IgG seroconversion detected by ELISA, and viral RNA isolation confirmed by RT
      qPCR and qualitative nested RT-PCR. BM biopsies were collected from all animals,
      submitted to histology and indirect immunofluorescence techniques and observed,
      respectively, by light and confocal microscopy. The HEV Ag-fluorescent-labeled
      cells were detected from BM biopsies obtained from three monkeys with acute and
      one with chronic hepatitis E, and also from the naturally infected monkey. In the
      experimentally infected animals with acute hepatitis, HEV Ag detection occurred
      at 160 days post-infection, even after viral clearance in serum, feces, and
      liver. Double-stranded RNA, a replicative marker, was detected in BM cells from
      both acute and chronically infected animals. Major histological findings included
      vacuolization in mononuclear and endosteal cells, an absence of organized
      inflammatory infiltrates, and also some fields suggesting displasic focal BM
      disease. These findings support the hypothesis of BM cells as secondary target
      sites of HEV persistence. Further experimental studies should be carried out to
      confirm the assumption of HEV transmission through BM transplantation.

PMID- 30278078
TI  - Retraction: Mitochondrial Dysfunction Promotes Breast Cancer Cell Migration and
      Invasion through HIF1alpha Accumulation via Increased Production of Reactive
      Oxygen Species.

PMID- 30278077
TI  - Exploring facilitators and barriers to medication error reporting among
      healthcare professionals in Qatar using the theoretical domains framework: A
      mixed-methods approach.
AB  - BACKGROUND: There is a need for theory informed interventions to optimise
      medication reporting. This study aimed to quantify and explain behavioural
      determinants relating to error reporting of healthcare professionals in Qatar as
      a basis of developing interventions to optimise the effectiveness and efficiency
      of error reporting. METHODS: A sequential explanatory mixed methods design
      comprising a cross-sectional survey followed by focus groups in Hamad Medical
      Corporation, Qatar. All doctors, nurses and pharmacists were invited to complete
      a questionnaire that included items of behavioural determinants derived from the
      Theoretical Domains Framework (TDF), an integrative framework of 33 theories of
      behaviour change. Principal component analysis (PCA) was used to identify
      components, with total component scores computed. Differences in total scores
      among demographic groupings were tested using Mann-Whitney U test (2 groups) or
      Kruskal-Wallis (>2 groups). Respondents expressing interest in focus group
      participation were sampled purposively, and discussions based on survey findings
      using the TDF to provide further insight to survey findings. Ethical approval was
      received from Hamad Medical Corporation, Robert Gordon University, and Qatar
      University. RESULTS: One thousand, six hundred and four questionnaires were
      received (67.9% nurses, 13.3% doctors, 12.9% pharmacists). Questionnaire items
      clustered into six components of: knowledge and skills related to error
      reporting; feedback and support; action and impact; motivation; effort; and
      emotions. There were statistically significant higher scores in relation to age
      (older more positive, p<0.001), experience as a healthcare professional (more
      experienced most positive apart from those with the highest level of experience,
      p<0.001), and profession (pharmacists most positive, p<0.05). Fifty-four
      healthcare professionals from different disciplines participated in the focus
      groups. Themes mapped to nine of fourteen TDF domains. In terms of emotions, the
      themes that emerged as barriers to error reporting were: fear and worry on
      submitting a report; that submitting was likely to lead to further investigation
      that could impact performance evaluation and career progression; concerns over
      the impact on working relationships; and the potential lack of confidentiality.
      CONCLUSIONS: This study has quantified and explained key facilitators and
      barriers of medication error reporting. Barriers appeared to be largely centred
      on issues relating to emotions and related beliefs of consequences. Quantitative
      results demonstrated that while these were issues for all healthcare
      professionals, those younger and less experienced were most concerned.
      Qualitative findings highlighted particular concerns relating to these emotional
      aspects. These results can be used to develop theoretically informed
      interventions with the aims of improving the effectiveness and efficiency of the
      medication reporting systems impacting patient safety.

PMID- 30278079
TI  - Characterization of the blastogenic response to LPS of bovine peripheral blood
      mononuclear cells.
AB  - Mitogens are diverse compounds of plant and microbial origin, widely employed to
      test immunocompetence in animals. The blastogenic response of bovine Peripheral
      Blood Mononuclear Cells (PBMC) to lypopolysaccharides (LPS) has been investigated
      in our laboratories for a long time. In particular, a possible correlation
      between blastogenic response to LPS and disease resistance of periparturient
      dairy cows had been observed in previous studies. Most important, low responder
      cows presented a higher frequency of disease cases after calving, compared with
      high responder animals. Owing to the above, different aspects of the blastogenic
      response to LPS were investigated on PBMC of healthy Friesian cows, using a 72
      hour Bromodeoxyuridin (BrDU) cell proliferation assay. Stimulation with LPS
      induced little if any replication of bovine PBMC over 72 hours despite consistent
      BrDU detection in all the PBMC samples under study. Poor replication of LPS
      stimulated PBMC was confirmed by cell cycle and cell growth flow cytometry
      analyses. In particular, LPS stimulation gave rise to very low percentages of S
      phase cells, sometimes lower than in control, unstimulated cells, as opposed to
      Concanavalin A-stimulated PBMC. Magnetic separation and analysis of BrDU-treated
      bovine PBMC after exposure to LPS showed that both B and CD4 T cells are involved
      in the blastogenic response to LPS, in contrast with current data based on human
      and murine models. Finally, LPS caused an early, specific up-regulation of TNF
      alpha and TLR4 genes in bovine PBMC, and significant correlations were shown
      between the expression of inflammatory cytokine and Indoleamine-pyrrole 2,3
      dioxygenase (IDO1) genes. On the whole, our data indicate that differences in the
      blastogenic response to LPS could be partly accounted for by heterogenicity of
      responding cells (B and T lymphocytes), which might also have an impact on
      induction and regulation of inflammatory responses and endotoxin tolerance.

PMID- 30278080
TI  - Correction: Novel high-resolution computed tomography-based radiomic classifier
      for screen-identified pulmonary nodules in the National Lung Screening Trial.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0196910.].

PMID- 30278081
TI  - Development of a scale to assess motivation for competitive employment among
      persons with severe mental illness.
AB  - BACKGROUND: The employment rate among people with severe mental illness has
      recently increased, though it is still low. The motivation to work appears to be
      an important role as an intermediate outcome measure in vocational rehabilitation
      programs. In addition, measuring the work motivation for people with severe
      mental illness appears to be essential to identify candidates who are likely to
      benefit and monitor candidates' motivation in a supported employment program.
      This study aimed to develop a new measure for assessing both intrinsic and
      extrinsic motivation to work among people with severe mental illness, as there
      are currently no well-established instruments of this kind. METHODS: A focus
      group interview and review of previous qualitative research were used to identify
      possible items for inclusion in the new scale. A provisional scale was
      constructed and further refined for content and format based on feedback from a
      researcher and also three peer workers with severe mental illness. The resulting
      provisional 38-item version of the scale was completed by 136 respondents with
      severe mental illness, and we performed exploratory factor analysis to identify
      latent constructs within the new measure. The finalized scale was analyzed for
      test-retest reliability, internal consistency, and convergent validity. RESULT:
      An exploratory factor analysis yielded a four-factor scale with 23 items. The
      finalized 23 items had high internal consistency (Cronbach's alpha = 0.91) and
      relatively high test-retest reliability (ICC = 0.83). The four subscales had fair
      internal consistency (Cronbach's alpha >= 0.69) and good test-retest reliability
      (ICC >= 0.61). Convergent validity was weakly supported by the significant
      positive correlations with the overall question on motivation to work (r >= 0.19,
      p < 0.01). Besides these correlations, only the "Pressure from others" subscale
      was negatively and significantly correlated with the negative symptoms evaluated
      using the Positive and Negative Syndrome Scale (r = -0.18, p = 0.04).
      CONCLUSIONS: This study used factor analysis to develop a new multidimensional
      scale assessing motivation for competitive employment among persons with severe
      mental illness. The scale showed acceptable levels of reliability and factor
      based and convergent validity. The new measure can be used for measuring the
      motivation for competitive employment among people with severe mental illness,
      and it would be useful to identify candidates who are likely to benefit from a
      certain supported employment program, and to monitor interim progress of the
      state of participants' motivation in a program.

PMID- 30278082
TI  - A low meat diet increases the risk of open-angle glaucoma in women-The results of
      population-based, cross-sectional study in Japan.
AB  - BACKGROUND: Studies identifying modifiable lifestyle risk factors related to open
      angle glaucoma (OAG) are limited, especially from Asian countries. This study
      aimed to identify lifestyle risk factors for OAG in a Japanese population.
      METHODS AND FINDINGS: This population-based, cross-sectional study recruited
      Japanese participants aged 40 years or older from January 2013 to March 2015. We
      took fundus photographs for OAG screening, determined lifestyle and health
      characteristics through a questionnaire and performed physical examinations. The
      participants who had suspect findings in the fundus photographs were sent for a
      detailed ophthalmic examination to diagnose OAG. Lifestyle and heath
      characteristics were statistically compared between the OAG and non-OAG
      participants. A total of 1583 participants were included in the study, of which
      42 had OAG and 1541 did not have OAG. The number of days per week that the female
      participants consumed meat (mean+/-SD; OAG: 1.7+/-1.2 days, non-OAG: 2.7+/-1.5
      days) was negatively associated with OAG (OR = 0.61; 95% CI: 0.43-0.88; p =
      0.007). Higher intraocular pressure was positively associated with OAG in men (OR
      = 1.20; 95% CI: 1.05-1.38, p = 0.009). No significant difference between
      participants with and without OAG was observed for a range of other lifestyle
      factors and health criteria including self-report of diabetes, number of family
      living together, body mass index, blood pressure, pulse rate, coffee drinking,
      tea drinking, alcohol drinking, number of fruits consumed per day and days of
      fish consumption per week. CONCLUSIONS: A higher weekly consumption of meat
      appears to be negatively associated with OAG in Japanese women. Increasing the
      dietary intake of meat can contribute to reducing the risk of developing OAG.

PMID- 30278083
TI  - Virtual reality assessment of walking and non-walking space in men and women with
      virtual reality-based tasks.
AB  - Far space and near space refer to different spatial features in which we unfold
      our behaviour. On the one hand, classical visuospatial neuropsychological tests
      assess spatial abilities in the near space; on the other, far space typically
      involves new spatial memory tasks in which participants display their behaviour
      in an environment, either interacting with objects or searching for targets. The
      Boxes Room Task is a virtual test that assesses spatial memory in the far space.
      Based upon this task, a new test was developed in which participants could not
      move about within the context, but they could actually perceive it from a
      specific viewpoint. In this work, both versions of the task were compared with
      one another. Furthermore, they were also compared with the results of 10/36
      spatial recall test, a task assessing spatial memory in the near space. Two
      conditions were applied in all tasks, both in stable and rotated contexts. Our
      study included one hundred and twenty healthy young participants who were divided
      into two groups. The first group performed the Walking Space Boxes Room Task. A
      second group performed the Non-Walking Space Boxes Room Task as well as another
      traditional neuropsychological test for near space assessment, the 10/36 spatial
      recall test. Results proved that orientation in the non-walking space was more
      difficult than in the walking space. Additionally, our test also showed that men
      outperformed women in both virtual reality-based tasks, although they did not do
      it in the traditional 10/36 spatial recall test. In short, this work exposes that
      virtual-reality technologies provide tools to assess spatial memory, being more
      sensitive than traditional tests in the detection of small performance changes.

PMID- 30278084
TI  - Retraction: Anti-Tumor Activity of a Novel Compound-CDF Is Mediated by Regulating
      miR-21, miR-200, and PTEN in Pancreatic Cancer.

PMID- 30278085
TI  - Correction: Genome-Wide Association Study on Male Genital Shape and Size in
      Drosophila melanogaster.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0132846.].

PMID- 30278086
TI  - Utilization of bambara groundnut (Vigna subterranea (L.) Verdc.) for sustainable
      food and nutrition security in semi-arid regions of Zimbabwe.
AB  - Bambara groundnut (Vigna subterranea (L.) Verdc.) is an indigenous legume crop,
      cultivated by subsistence farmers throughout sub-Saharan countries. Research
      findings indicate that the crop has great nutritional and agronomic potential,
      but it remains scientifically neglected. A baseline study was conducted in seven
      districts in semi-arid regions of rural Zimbabwe to gather knowledge on current
      production and utilization of bambara groundnut, assess its role in providing
      sustainable food and nutrition security for rural populations and determine
      priorities for follow-up research. Results revealed a variety of bambara
      groundnut processing techniques, which included boiling, soaking, roasting and
      milling across the surveyed districts. Reported constraints to processing and
      consumption included long cooking time, difficulties with milling and high
      firewood and water requirements. Fifty to eighty percent of respondents in all
      districts consumed bambara groundnut once or twice weekly from August to
      December. Preferred consumer attributes were taste, the satiating effect,
      nutritional benefits or a combination of these. Current, culturally acceptable
      processing techniques need improvement to support sustainable bambara groundnut
      processing while optimising nutrient bio-accessibility. Ultimately, community
      resilience to food and nutrition insecurity can be promoted by exchange of
      bambara groundnut processing knowledge amongst the production areas, involving
      the different stakeholders in the food supply chains.

PMID- 30278088
TI  - Evaluation and evolution of bank efficiency considering heterogeneity technology:
      An empirical study from China.
AB  - The performances of different types of banks may vary due to heterogeneous
      technology, which can be examined by metafrontier analysis. However, the
      metafrontier constructed in most existing literature is concave, resulting in a
      biased estimation of efficiency. Based on 93 Chinese commercial banks over the
      period of 2005-2016, we first evaluate the banking efficiency by using the
      proposed data envelopment analysis (DEA) model, NCMeta-US-NSBM, which
      simultaneously incorporates a non-concave metafrontier technique, undesirable
      outputs, and super efficiency into a network slacks-based measure (NSBM) model.
      Subsequently, the evolution of banking efficiency during the study period is
      investigated on the basis of the Dagum Gini index and kernel density estimation
      methods. The main empirical results show the following. 1) There exists
      significant disparity/heterogeneity in banking efficiency for overall efficiency,
      productivity efficiency, and profitability efficiency. 2) The results of the
      technology gap ratio (TGR) and the evaluation of stated-owned banks (SOB), joint
      stock banks (JSB), and city commercial banks (CCB) in the productivity stage are
      higher than those in the profitability stage, indicating that most of the banks
      have a large space for improvement, especially for SOB and JSB in the
      profitability stage. 3) The major contribution of the overall difference of
      banking efficiency in China is the intensity of the transvariation. 4) Although
      the kernel density estimations for different efficiency scores have similar
      distributions in corresponding years, the multilevel differentiation phenomenon
      of banking efficiency may appear after 2008.

PMID- 30278087
TI  - Body condition and adrenal glucocorticoid activity affects metabolic marker and
      lipid profiles in captive female elephants in Thailand.
AB  - Studies in western zoo elephants have found relationships between body condition
      and physiological function, and identified mitigating management strategies to
      optimize health and welfare. A similar methodological approach was used in this
      study, which evaluated a body condition score (BCS; 1 = thinnest, 5 = fattest)
      every other month and fecal glucocorticoid metabolite (FGM) concentrations twice
      monthly in 33 tourist camp elephants in Thailand for a 1-year period to assess
      seasonal variations, and determine how lipid profiles [total cholesterol (TC),
      low density lipoproteins (LDL), high density lipoproteins (HDL), triglycerides
      (TG)] and metabolic parameters [insulin, glucose, fructosamine, glucose to
      insulin ratio (G:I)] related to measures of body condition and adrenal function.
      The most prevalent BCS was 3-3.5 (60.6%), with 27.3% at BCS = 4 (overweight) and
      12.1% at BCS = 4.5-5 (very overweight); no elephants had a BCS <2. BCSs were
      higher in rainy and winter seasons compared to summer, with FGM, TG, HDL, LDL,
      and insulin also higher in the rainy and/or winter seasons (p<0.05). By contrast,
      TC and glucose were lowest in the rainy season. FGM measures were negatively
      associated with two environmental factors: temperature and rainfall, but not
      humidity. Positive correlations were found between BCS and TC, LDL, and HDL, and
      between FGM and TC, HDL, glucose, and insulin (p<0.05), whereas BCS and FGM were
      both negatively associated with the G:I (p<0.05). However, there was no
      relationship between BCS and FGM among the camp elephants. Using BCS and FGM
      measures as outcome variables in separate regression models, this study found
      high BCS and elevated FGM concentrations were associated with altered lipid
      profiles and metabolic status in elephants. Furthermore, more work hours/day was
      associated with better body condition and health measures. Thus, being overweight
      and exposed to factors that increase adrenal activity could adversely affect
      health status, requiring alterations in management for some individuals, whereas
      exercise appears to have a protective effect.

PMID- 30278090
TI  - Retraction: Up-Regulation of Sonic Hedgehog Contributes to TGF-beta1-Induced
      Epithelial to Mesenchymal Transition in NSCLC Cells.

PMID- 30278089
TI  - Trace metals, organic carbon and nutrients in the Beidagang Wetland Nature
      Reserve, northern China.
AB  - This study aimed to determine sediment contamination in the Beidagang Wetland
      Nature Reserve to describe atmospheric deposition of trace metals. We analyzed
      Hg, Cd, Pb, TOC, TN, TP, delta13C, and delta15N, and studied their variations in
      surface sediments and in the vertical profiles of sediment cores collected from
      the reserve. Evaluation of environmental trace metal contamination using sediment
      quality guidelines and geochemical background values indicated that the risk of
      metal pollution in the reserve sediments was relatively low. Concentrations of
      Hg, Cd, and Pb in the sediments were much lower than concentrations in sediment
      samples from Bohai Bay and polluted rivers in Tianjin. Enrichment factors
      indicate that samples are moderately contaminated with Hg, Cd, and Pb; whereas
      the geo-accumulation index results classify the sediments as uncontaminated to
      moderately contaminated with Hg, Cd, and Pb. The distribution patterns of trace
      metal concentrations in the three core samples were uniform. delta13C and
      delta15N were used to track the sources of TOC and TN in sediments. Results show
      that TOC mainly originated from the residue and decaying matter of aquatic plants
      (e.g., algae, reeds, and Typha), while TN was derived from soil N and elevated
      atmospheric N deposition. Because domestic and industrial waste is not discharged
      into the Beidagang Wetland Nature Reserve, trace metals found in sediments mainly
      originate from atmospheric deposition. The results provide baseline data for
      analysis of trace metal accumulation in Beijing-Tianjin-Hebei, a region subject
      to atmospheric deposition in northern China.

PMID- 30278091
TI  - Correction: Karnatukul (Serpent's Glen): A new chronology for the oldest site in
      Australia's Western Desert.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0202511.].

PMID- 30278093
TI  - Assisting Individuals With Intellectual Disabilities: Do We, as Nurses, Still
      Have a Role?

PMID- 30278094
TI  - FDA-Approved Drugs to Treat Sleep Disorders.

PMID- 30278095
TI  - Ketamine for Treatment-Resistant Depression: A Gateway to Novel Treatment
      Approaches.
AB  - Treatment-resistant depression (TRD) is a disabling and demoralizing phenomenon
      for patients and clinicians. For many years, treatment for depression has relied
      on the monoamine theory, with medications limited in efficacy and requiring
      prolonged use before any therapeutic effects are evident. The current article
      reviews novel approaches to pharmacological treatment of TRD, including N-methyl
      D-aspartate glutamate receptor antagonists and other receptor agonists and
      antagonists beyond serotonin and norepinephrine. [Journal of Psychosocial Nursing
      and Mental Health Services, 56(10), 11-14.].

PMID- 30278096
TI  - Informal Grandmother Caregivers of Co-Resident Young Adult Grandchildren.
AB  - Although primary caregivers of young adult grandchildren are generally not older
      women, a limited number of aged grandmothers assume this critical role. It is
      beneficial for the public to understand the lived experiences of these
      caregivers. For many different reasons, older grandmother caregivers freely
      provide valuable, person-centered care in their homes. They respond, on an
      ongoing basis, to the many care needs of their young adult grandchildren. Over
      time, their caregiving experiences can be satisfying and challenging. Because
      their services are provided to their young adult grandchildren at home, the
      collaborative efforts of health professionals, caregivers, and care recipients
      are essential. Therefore, researchers and health professionals can use conceptual
      models that emphasize wholeness, unity, and collaborative decision making to
      frame their understanding of the phenomenon of older grandmother caregivers,
      consider the influential factors, and determine the practice implications for
      this population. [Journal of Psychosocial Nursing and Mental Health Services,
      56(10), 15-19.].

PMID- 30278097
TI  - "Miniature" by Bijan Naderi.

PMID- 30278092
TI  - Molecular dynamics provides insight into how N251A and N251Y mutations in the
      active site of Bacillus licheniformis RN-01 levansucrase disrupt production of
      long-chain levan.
AB  - Produced by levansucrase, levan and levan oligosaccharides (GFn) have potential
      applications in food and pharmaceutical industries such as prebiotics, anti-tumor
      and anti-inflammatory agents. Previous study reported that Bacillus licheniformis
      RN-01 levansucrase could produce levan oligosaccharides and long-chain levan.
      However, its N251A and N251Y mutants could effectively produce short-chain
      oligosaccharides upto GF3, but they could not produce long-chain levan. We
      hypothesized that these mutations probably reduced GF3 binding affinity in
      levansucrase active site that contains fructosyl-Asp93 intermediate and caused
      GF3 to be in an unfavorable orientation for transfructosylation; therefore,
      levansucrase could not effectively extend GF3 by one fructosyl residue to produce
      GF4 and subsequently long-chain levan. However, these mutations probably did not
      significantly reduce binding affinity or drastically change orientation of GF2;
      therefore, levansucrase could still extend GF2 to produce GF3. Using this
      hypothesis, we employed molecular dynamics to investigate effects of these
      mutations on GF2/GF3 binding in levansucrase active site. Our results reasonably
      support this hypothesis as N251A and N251Y mutations did not significantly reduce
      GF2 binding affinity, as calculated by MM-GBSA technique and hydrogen bond
      occupations, or drastically change orientation of GF2 in levansucrase active
      site, as measured by distance between atoms necessary for transfructosylation.
      However, these mutations drastically decreased GF3 binding affinity and caused
      GF3 to be in an unfavorable orientation for transfructosylation. Furthermore, the
      free energy decomposition and hydrogen bond occupation results suggest the
      importance of Arg255 in GF2/GF3 binding in levansucrase active site. This study
      provides important and novel insight into the effects of N251A and N251Y
      mutations on GF2/GF3 binding in levansucrase active site and how they may disrupt
      production of long-chain levan. This knowledge could be beneficial in designing
      levansucrase to efficiently produce levan oligosaccharides with desired length.

PMID- 30278098
TI  - Internal Validation of RapidHIT(r) ID ACE Sample Cartridge and Assessment of the
      EXT Sample Cartridge*?.
AB  - A new rapid DNA solution, the RapidHIT(r) ID, can accommodate two different
      sample cartridges, ACE, for the analysis of a single swab and EXT, for the
      analysis of DNA extracts. An efficient internal validation designed for low
      throughput rapid DNA is described. An evaluation of the EXT sample cartridge is
      also described. Each cartridge generated profiles with sufficient data quality to
      meet CODIS eligibility in fewer than 120 min. The results exhibited 100%
      correlation when compared to conventional DNA typing methods. Precision,
      reproducibility, stochastic, mixture, and contamination experiments produced
      expected results. Sensitivity of the ACE sample cartridge was acceptable for
      buccal swab analysis. The sensitivity of the EXT sample cartridge is discussed.
      The ACE validation and the EXT evaluation utilized a minimalist, cost-saving,
      efficient design to generate a validated RapidHIT(r) ID instrument capable of
      producing genetic profiles from both extracted forensic DNA samples and buccal
      swab samples within 120 min.

PMID- 30278099
TI  - Apigenin as an effective anticancer natural product: Spotlight on TRAIL, WNT/beta
      catenin, JAK-STAT pathways, and microRNAs.
AB  - Wealth of information gleaned from decades of high-impact research work;
      scientists have disentangled the complicated web of versatile regulators that
      underlie cancer development and progression. Use of structural biology approaches
      and functional genomics have helped us to gain new insights into complex nature
      of cancer, and it is now clear that genetic/epigenetic mutations, overexpression
      of oncogenes, inactivation of tumor suppressors, loss of apoptosis, and
      versatility of protein binding partners have contributory roles in carcinogenesis
      and metastatic spread. It is becoming progressively more understandable that
      reprogramming of gene expression during and nontranscriptional changes during
      cancer development and progression are initiated and controlled by deregulated
      signal transduction cascades, all of which collectively create an incalculable
      complexity. Data obtained through preclinical and clinical trials revealed that
      alterations in the targeted oncogenes and other downstream, and parallel pathways
      played a central role in the development of resistance against different
      therapeutics. Phytochemicals have regained limelight, and different natural
      products are currently being tested for efficacy in preclinical studies.
      Apigenin, a plant-derived flavonoid has considerable pharmacological value and is
      reportedly involved in the regulation of different signaling cascades. In this
      review, we have attempted to summarize rapidly evolving understanding of
      molecular biologists and pharmacologists about the potential of apigenin in the
      regulation of deregulated signaling pathways in different cancers. We have
      emphasized on the regulation of WNT/beta-catenin and janus kinase/signal
      transducers and activators of transcription (JAK-STAT) pathways. We also
      comprehensively discuss how apigenin restored apoptosis in tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL)-resistant cancers. The review also
      gives a snapshot of microRNAs (miRNAs) that regulate wide-ranging biological
      processes, and it is now clear that each miRNA can control hundreds of gene
      targets. Apigenin was noted to upregulate miR-520b and miR-101 in different
      cancers to inhibit tumor growth. Moreover, apigenin-induced apoptotic rate was
      significantly higher when used in combination with miR-423-5p inhibitors or miR
      138 mimics. Better comprehension of linear and integrated signaling pathways will
      be helpful in effective therapeutic targeting of deregulated signaling pathways
      to inhibit/prevent cancer.

PMID- 30278100
TI  - Feigning Hand Preference? A Case Report Preliminary Data.
AB  - Hand preference may be crucial in the forensic domain, notably in cases where the
      assailant is known to be left-handed and the defendant claims to be right-handed
      (or vice versa). In such cases, forensic psychologists or physicians may be asked
      to test the hand preference of the defendant. However, hand preference may be
      faked. The case described here illustrates this problem and addresses potential
      solutions. We also present preliminary data showing that a standard instrument
      for measuring handedness is sensitive to feigning. We conclude that when hand
      preference is determined, multiple sources of information should be assessed in
      order to identify possible feigning.

PMID- 30278101
TI  - Methanol Detected in a Subdural Hematoma as an Embalming Artifact.
AB  - Analysis of subdural hematomata has been used to suggest antemortem drug
      concentrations, with the assumption that materials within the hematoma are less
      subject to metabolism or degradation during any survival period and postmortem
      interval. We report the case of an 87-year-old woman whose death had not been
      reported to the coroner's office until postembalming. Autopsy revealed a
      traumatic brain injury with subdural hematoma causing a mass effect. Testing of
      the clot indicated a methanol concentration of 51.8 mg%. No additional analyses
      were detected. These findings suggest that methanol can be present in a
      postmortem hematoma sample, yet not represent a poisoning. Our findings also
      suggest that while the interior of hematomata do not necessarily represent
      completely "protected space" from postmortem diffusion of some blood
      constituents, such diffusion is not facile, and analysis may still provide useful
      indications of antemortem drugs present, if not actual concentrations.

PMID- 30278102
TI  - Haemolysin Sph2 of Leptospira interrogans induces cell apoptosis via
      intracellular reactive oxygen species elevation and mitochondrial membrane
      injury.
AB  - Leptospira interrogans causes widespread leptospirosis in humans and animals,
      with major symptoms of jaundice and haemorrhage. Sph2, a member of the
      sphingomyelinase haemolysins, is an important virulence factor for leptospire. In
      this study, the function and mechanism of Sph2 in the pathogenesis of
      leptospirosis were investigated to further understand the pathogenesis of
      leptospire. Real-time PCR analysis of expression levels during cell invasion
      showed that sph2 gene expression was transiently induced in human umbilical vein
      endothelial cells (HUVECs), human embryo liver cells (L02), and human epithelial
      lung cells (L132), with expression levels reaching a peak after 45 min of
      infection. Further functional analysis of recombinant Sph2 (rSph2) by LDH assays
      and confocal microscopy showed that rSph2 can be internalised by cells both by
      causing cell membrane damage and by a damage-independent clathrin-mediated
      endocytosis pathway. Subsequently, rSph2 is able to translocate to mitochondria,
      which led to an increase in the levels of reactive oxygen species (ROS) and a
      decrease of the mitochondrial membrane potential (DeltaPsim ). Further
      flowcytometry analyses after rSph2 exposure showed that 28.7%, 31%, and 27.3% of
      the HUVEC, L02, and L132 cells, respectively, became apoptotic. Because apoptosis
      could be decreased with the ROS inhibitor N-acetyl cysteine, these experiments
      suggested that rSph2 triggers apoptosis through mitochondrial membrane damage and
      ROS elevation. The ability of leptospiral haemolysin rSph2 to cause apoptosis
      likely contributes to the pathogenesis of leptospirosis.

PMID- 30278103
TI  - miR-345-5p regulates proliferation, cell cycle, and apoptosis of acute myeloid
      leukemia cells by targeting AKT2.
AB  - Acute myeloid leukemia (AML) is a malignant clonal hematopoietic disease, which
      is caused by hematopoietic stem cell abnormalities. Epigenetic regulation,
      especially of microRNAs (miRNAs), mostly results from external or environmental
      effects and is critical to AML. In this study, for the first time, we report that
      decreased expression of miR-345-5p facilitates the proliferation of leukemia
      cells in AML. Further study demonstrated that AKT1/2 was the target of miR-345-5p
      and was responsible for the dysregulation of leukemia cell proliferation and
      apoptosis. Inhibition of AKT1/2 ameliorated this malignant effect, which provides
      new insight into AML diagnosis, treatment, prognosis, and next-step translational
      investigations.

PMID- 30278104
TI  - PIP2 Phospholipid-Induced Aggregation of Tau Filaments Probed by Tip-Enhanced
      Raman Spectroscopy.
AB  - The morphology and secondary structure of peptide fibers formed by aggregation of
      tubulin-associated unit (Tau) fragments (K18), in the presence of the inner
      cytoplasmic membrane phosphatidylinositol component (PIP2 ) or heparin sodium
      (HS) as cofactors, are determined with nanoscale (<10 nm) spatial resolution. By
      means of tip-enhanced Raman spectroscopy (TERS), the inclusion of PIP2 lipids in
      fibers is determined based on the observation of specific C=O ester vibration
      modes. Moreover, analysis of amide I and amide III bands suggests that the
      parallel beta-sheet secondary structure content is lower and the random coil
      content is higher for fibers grown from the PIP2 cofactor instead of HS. These
      observations highlight the occurrence of some local structural differences
      between these fibers. This study constitutes the first nanoscale structural
      characterization of Tau/phospholipid aggregates, which are implicated in
      deleterious mechanisms on neural membranes in Alzheimer's disease.

PMID- 30278105
TI  - Acupuncture as a multifunctional neuroprotective therapy ameliorates cognitive
      impairment in a rat model of vascular dementia: A quantitative iTRAQ proteomics
      study.
AB  - AIMS: Acupuncture has been reported to affect vascular dementia through a variety
      of molecular mechanisms. An isobaric tag for relative and absolute quantification
      (iTRAQ) with high-resolution liquid chromatography-tandem mass spectrometry (LC
      MS/MS) analyses makes it possible to attain a global profile of proteins. Hence,
      we used an iTRAQ-LC-MS/MS strategy to unravel the underlying mechanism of
      acupuncture. METHODS: Wistar rats were subjected to vascular dementia with
      bilateral common carotid occlusion. Acupuncture was intervened for 2 weeks at 3
      days after surgery. The Morris water maze was used to assess the cognitive
      function. Proteins were screened by quantitative proteomics and analyzed by
      bioinformatic analysis. Four differentially expressed proteins (DEPs) were
      validated by western blot. The reactive oxygen species (ROS) production, neuron
      cell loss, and long-term potentiation (LTP) were determined after western blot.
      RESULTS: Acupuncture at proper acupoints significantly improved cognitive
      function. A total of 31 proteins were considered DEPs. Gene ontology (GO)
      analysis showed that most of the DEPs were related to oxidative stress,
      apoptosis, and synaptic function, which were regarded as the major cellular
      processes related to acupuncture effect. Western blot results confirm the
      credibility of iTRAQ results. Acupuncture could decrease ROS production, increase
      neural cell survival, and improve LTP, which verified the three major cellular
      processes. CONCLUSION: Acupuncture may serve as a promising clinical candidate
      for the treatment of vascular dementia via regulating oxidative stress,
      apoptosis, or synaptic functions.

PMID- 30278107
TI  - Searching for Kin Amidst Tragedy-Disaster Victim Identification Operations for US
      Bangla Flight 211.
AB  - The nature of air disasters includes factors that exacerbate challenges in the
      identification process. Of the 49 deceased in the US Bangla air crash in
      Kathmandu, Nepal, four were intact, 11 presented with burn injuries, another 11
      presented with partial charring, and 23 were completely charred. Personal
      belongings were useful in the identification phases for all types of victims.
      Fingerprints were obtainable and useful in intact victims and victims with less
      severe burn injuries; medical and surgical information was useful in bodies with
      burn injuries; finally, dental findings were useful in cases of extensive
      charring. Other useful methods in the process included marks of identification,
      physical features, and exclusion. In certain resource-limited settings,
      especially in closed population disasters, where scientific identification (DNA,
      dental records, etc.) is not currently available, personal belongings, clothing,
      and physical findings analyzed by an identification team using a structured
      organization may be cautiously used as the primary means of identification.

PMID- 30278106
TI  - Magnetic compression anastomosis for biliojejunostomy and pancreaticojejunostomy
      in Whipple's procedure: An initial clinical study.
AB  - BACKGROUND AND AIM: Magnetic anastomosis has been attempted in biliary and
      intestinal reconstruction. The objective of the current study was to introduce an
      initial clinical use of magnetic compression anastomosis for
      pancreaticojejunostomy and biliojejunostomy in Whipple's procedure. METHODS:
      Patients with peri-ampullary carcinoma and dilated bile and pancreatic ducts were
      prospectively enrolled from 2016 to 2017. After pancreaticoduodenectomy, an
      appropriate mother magnet and drainage tube was placed in the proximal bile duct
      and pancreatic duct. The daughter magnets were introduced to mate with the mother
      magnets at the anastomotic sites. A close postoperative surveillance and routine
      cholangiopancreaticography via the drainage tube were performed. RESULTS: One
      female and three male patients with a median age of 69 years (range, 57-77) were
      included. The diameter of the common bile ducts and pancreatic ducts ranged from
      8 to 15 mm, and 7 to 10 mm, respectively. The median time duration for
      biliojejunostomy and pancreaticojejunostomy was 7 (range, 5-8 min) min and 9
      (range, 8-10 min) min, respectively. The median time of biliojejunostomy and
      pancreaticojejunostomy formation was 17 (range, 15-21 days) days and 11 (range,
      10-18 days), respectively. With a median follow up of 313 days, one patient
      developed biliary anastomotic stricture at 11 months after surgery, and underwent
      stent placement via percutaneous transhepatic drainage sinus, and recovered well.
      CONCLUSIONS: Magnetic anastomosis is safe, effective, and simple for both
      biliojejunostomy and pancreaticojejunostomy in Whipple's procedure.

PMID- 30278108
TI  - The phenomenon of lipid metabolism "cut" mutants.
AB  - Every cell cycle iteration culminates with the resolution of a mitotic nucleus
      into a pair of daughter nuclei, which are distributed between the two daughter
      cells. In the fission yeast Schizosaccharomyces pombe, the faithful division of a
      mitotic nucleus depends on unperturbed lipogenesis. Upon genetically or
      chemically induced perturbation of lipid anabolism, S. pombe cells fail to
      separate the two daughter nuclei and subsequently initiate lethal cytokinesis
      resulting in the so-called "cut" terminal phenotype. Evidence supporting a
      critical role of lipid biogenesis in successful mitosis in S. pombe has been
      accumulating for almost two decades, but the exact mechanism explaining the
      reported observations had been elusive. Recently, several studies established a
      functional link between biosynthesis of structural phospholipids, nuclear
      membrane growth, and the fidelity of "closed" mitosis in S. pombe. These novel
      insights suggest a mechanistic explanation for the mitotic defects characteristic
      for some S. pombe mutants deficient in lipid anabolism and extend our knowledge
      of metabolic modulation within the context of the cell cycle. In this review, we
      cover the essential role of lipogenesis in "closed" mitosis, focusing mainly on
      S. pombe as a model system.

PMID- 30278109
TI  - Insulin increases cholesterol uptake, lipid droplet content, and apolipoprotein B
      secretion in CaCo-2 cells by upregulating SR-BI via a PI3K, AKT, and mTOR
      dependent pathway.
AB  - : The actions of insulin on intestinal cholesterol absorption and lipoprotein
      secretion are not well understood. Herein, we determined the effects of insulin
      on the levels of cholesterol transporter scavenger receptor, class B, type I (SR
      BI), cellular cholesterol uptake, intracellular lipid accumulation, and
      lipoprotein secretion in a cellular model of human intestinal epithelium.
      METHODS: CaCo-2 cells were cultured to postconfluency in Transwell filters and
      stimulated with glucose (25 mM) in the presence or absence of insulin (100 nM) at
      their basolateral surface. SR-BI mRNA and protein levels were quantified by
      quantitative reverse transcription-PCR and immunoblot, respectively. Polarized
      localization of SR-BI was determined by cell surface proteins biotinylation and
      streptavidin precipitation. Activities of PI3K, AKT, mTOR, and SR-BI were
      pharmacologically antagonized. Cholesterol uptake was assessed by NBD-cholesterol
      incorporation. Apolipoprotein (apo) B concentration was quantified by ELISA.
      Subcellular localization of neutral lipids (BODIPY) and SR-BI
      (immunofluorescence) was determined by confocal microscopy. RESULTS: In polarized
      CaCo-2 cells, insulin increased SR-BI at the mRNA and protein levels. SR-BI was
      exclusively present at apical cell surface, as indicated by biotinylation and
      confocal microscopy analysis. Glucose did not modify SR-BI abundance or
      subcellular localization. Effects of insulin on SR-BI levels were abrogated by
      PI3K, AKT, or mTOR pharmacological antagonism. Cholesterol uptake, neutral lipid
      abundance, and apo B secretion were increased by insulin in CaCo-2 cells, and
      these effects were prevented by SR-BI pharmacological antagonism with block lipid
      transport-1. CONCLUSIONS: insulin promotes cholesterol uptake, intracellular
      lipid store, and apo B-containing lipoproteins secretion by SR-BI-dependent
      mechanisms in a model of human intestinal epithelium.

PMID- 30278110
TI  - Favorable outcomes of prepackaged low-residue diet on bowel preparation for
      colonoscopy: Endoscopist-blinded randomized controlled trial.
AB  - BACKGROUND AND AIM: 2 L polyethylene glycol plus an ascorbic acid (PEGA) is known
      to be as effective. However, 2 L polyethylene glycol-based regimens are often
      still difficult for patients to tolerate. Therefore, we conducted this study to
      evaluate the potential of 1 L PEGA with prepackaged low-residue diet (PLD) as an
      alternative to 2 L PEGA before colonoscopy. METHODS: The subjects were randomly
      assigned to either of the two groups. The 2 L PEGA group received 2 L PEGA split
      regimen. The 1 L PEGA with PLD group received PLD on the day preceding
      colonoscopy and 1 L PEGA. All endoscopic procedures were performed by one
      physician who did not know patients allocation. Bowel preparation status were
      graded using Boston Bowel Preparation Score (BBPS). A questionnaire regarding
      tolerability and safety was administered. This trial is registered at
      ClinicalTrials.gov (NCT03329339). RESULTS: A total of 173 patients completed the
      study (86 in the 2 L PEGA group and 87 in the 1 L PEGA with PLD group). Bowel
      preparation was adequate in 88.4% (76/86) of patients in the 2 L PEGA group and
      93.1% of patients in the 1 L PEGA with PLD group (81/87, P = 0.28). The patients
      in the 1 L PEGA with PLD group had higher whole Boston Bowel Preparation Scale
      score (P = 0.02) and expressed more satisfaction and willingness to repeat the
      procedure (P < 0.01). There was no significant difference with respect to
      compliance or safety. CONCLUSION: 1 L PEGA with PLD showed equivalent efficacy,
      greater satisfaction, and more willingness to repeat compared with 2 L PEGA for
      bowel preparation.

PMID- 30278111
TI  - L-carnitine prevents ammonia-induced cytotoxicity and disturbances in
      intracellular amino acid levels in human astrocytes.
AB  - BACKGROUND AND AIM: L-carnitine (L-CA) has been used therapeutically to treat
      hepatic encephalopathy with hyperammonemia, but the mechanism by which L-CA
      contributes to ammonia detoxification in the brain is still unclear. Thus, the
      cytotoxicity and changes in intracellular amino acids (AAs) in astrocytes with
      hyperammonemia following L-CA administration were studied. METHODS: Human
      astrocytes were treated with ammonium chloride (NH4 Cl), L-CA or a mixture of NH4
      Cl, and L-CA under defined conditions. Total intracellular reactive oxygen
      species and lactate dehydrogenase leakage were measured following different
      treatment periods. The intracellular levels of AAs in astrocytes were determined
      using metabolomic analysis. RESULTS: Intracellular total reactive oxygen species
      and lactate dehydrogenase leakage were significantly increased after treatment
      with NH4 Cl. In contrast, co-treatment with L-CA significantly inhibited the
      cytotoxic effects of NH4 Cl. The intracellular levels of almost all AAs involving
      glutamine and branched-chain AAs (BCAAs) were significantly increased in the NH4
      Cl-treated cells compared with in the control cells; these changes in BCAA levels
      were reduced with L-CA co-treatment. Additionally, the level of 3-methyl-2
      oxovaleric acid, which is a metabolite from isoleucine and plays a critical role
      in neurological damage, was significantly increased in the NH4 Cl-treated cells,
      but this metabolite was significantly decreased with L-CA co-treatment.
      CONCLUSION: L-CA protects human astrocytes from ammonia-induced acute cytotoxic
      effects and the increased intracellular levels of glutamine and BCAAs.

PMID- 30278112
TI  - Palladium-Catalyzed Enantioselective Addition of Chiral Metal Enolates to In Situ
      Generated ortho-Quinone Methides.
AB  - We describe herein a conceptually novel, cooperative Bronsted acid/base catalyzed
      process for the conjugate addition of cyclic beta-keto esters to ortho-quinone
      methides both generated in situ. Upon hemiacetalization, densely functionalized
      chiral chromans with two adjacent quaternary and additionally a tertiary
      stereogenic center were obtained with very good diastereoselectivity (up to >95:5
      d.r.) and typically excellent enantioselectivity (up to >99 % ee). The striking
      feature and key to success is the dual catalytic activation of both nucleophile
      and electrophile in two separate cycles with a single chiral catalyst.

PMID- 30278113
TI  - Construction and comprehensive analysis of dysregulated long non-coding RNA
      associated competing endogenous RNA network in clear cell renal cell carcinoma.
AB  - OBJECTIVE: This study aimed to assess the long noncoding RNA (lncRNA)-microRNA
      (miRNA)-messenger RNA (mRNA) regulatory network in clear cell renal cell
      carcinoma (ccRCC) by gene expression analyses. MATERIALS AND METHODS: LncRNA,
      miRNA, and mRNA expression profiles in ccRCC were obtained from The Cancer Genome
      Atlas. Differentially expressed lncRNAs, mRNAs (cut-off: |log 2 [fold change,
      FC])| > 2.0 and adjusted P < 0.01) and miRNAs (|log 2FC| > 1.5 and adjusted P <
      0.01) were unveiled using R. Cox regression analysis was performed to identify
      prognostic factors of ccRCC related to overall survival (OS). A protein-protein
      interaction (PPI) network was constructed for differentially expressed mRNAs
      (DEmRNAs) by Search Tool for the Retrieval of Interacting Genes (STRING). Key hub
      genes were screened from top 300 DEmRNAs. LncRNA-miRNA and miRNA-mRNA regulatory
      network were constructed and combined into the competing endogenous RNA
      regulatory network. Gene ontology biological terms were screened by STRING; Kyoto
      Encyclopedia of Genes and Genomes pathways were identified using the
      "clusterProfiler" package in R. RESULTS: A total of 2331, 1517, and 83 DEmRNAs,
      lncRNAs, and miRNAs were identified, respectively. Eleven lncRNAs (AC016773.1,
      HOTTIP, LINC00460, NALCN-AS1, PVT1, TRIM36-IT1, WT1-AS, COL18A1-AS1, LINC00443,
      LINC00472, and TCL6), three miRNAs (hsa-mir-21, hsa-mir-144, and hsa-mir-155),
      and three mRNAs (COL4A4, NOD2, and GOLGA8B) were associated with OS.
      Specifically, four lncRNAs (PVT1, LINC00472, TCL6, and WT1-AS1) and one mRNA
      (Collagen Type IV Alpha 4 Chain) were verified as independent prognostic factors
      by Gene Expression Profiling Interactive Analysis. Eleven key hub genes were
      obtained by PPI analysis. "Cell adhesion molecules (CAMs)," "chemical
      carcinogenesis," and "cytokine-cytokine receptor interaction" were significantly
      enriched in the network. CONCLUSION: The findings clarify the pathogenesis of
      ccRCC and might provide potential therapeutic targets.

PMID- 30278114
TI  - Terrorism Risk Assessment, Recollection Bias, and Public Support for
      Counterterrorism Policy and Spending.
AB  - Recollection bias (RB) refers to the phenomenon whereby after an adverse event
      people report that their risk assessment about a similar future event is
      presently no higher than their recollection of their pre-event risk assessment.
      While previous research has outlined this theoretical construct and generated
      important empirical findings, there were some limitations. We design and employ a
      new national representative survey to address these limitations in this study. We
      examine the existence and persistence of RB among the general public in the
      context of a number of domestic and international terrorist attacks. We further
      examine the socioeconomic and political base of RB and the influences of RB on a
      wide range of citizens' counterterrorism policy preferences. Our data analyses
      reveal strong evidence showing the occurrence of RB and its persistence across
      various forms of terrorism risk. With regard to the socioeconomic and political
      base, we find that females, older people, political conservatives, and
      Republicans are less likely to be subject to RB. For the effects of RB on public
      counterterrorism policy preferences, our analyses demonstrate that this bias
      significantly dampens public support for a wide range of preventive policy
      measures and government anti-terrorism spending. Overall, our study, based on a
      national representative sample and an extended survey design, provides robust
      evidence of RB in terrorism risk assessment, and adds further evidence to support
      the idea that RB is likely a generalizable phenomenon. Implications and
      suggestions for future research are discussed in the conclusion.

PMID- 30278115
TI  - Developing a Broadly Applicable Measure of Risk Perception.
AB  - Decades of research identify risk perception as a largely intuitive and affective
      construct, in contrast to the more deliberative assessments of probability and
      consequences that form the foundation of risk assessment. However, a review of
      the literature reveals that many of the risk perception measures employed in
      survey research with human subjects are either generic in nature, not capturing
      any particular affective, probabilistic, or consequential dimension of risk; or
      focused solely on judgments of probability. The goal of this research was to
      assess a multidimensional measure of risk perception across multiple hazards to
      identify a measure that will be broadly useful for assessing perceived risk
      moving forward. Our results support the idea of risk perception being
      multidimensional, but largely a function of individual affective reactions to the
      hazard. We also find that our measure of risk perception holds across multiple
      types of hazards, ranging from those that are behavioral in nature (e.g., health
      and safety behaviors), to those that are technological (e.g., pollution), or
      natural (e.g., extreme weather). We suggest that a general, unidimensional
      measure of risk may accurately capture one's perception of the severity of the
      consequences, and the discrete emotions that are felt in response to those
      potential consequences. However, such a measure is not likely to capture the
      perceived probability of experiencing the outcomes, nor will it be as useful at
      understanding one's motivation to take mitigation action.

PMID- 30278116
TI  - Exposure to parental and community violence and the relationship to bullying
      perpetration and victimization among early adolescents: A parallel process growth
      mixture latent transition analysis.
AB  - This study examined heterogeneity in parental and community violence exposure
      during middle school and its association with bullying perpetration and
      victimization in high school. Youth (N = 1,611) in four Midwestern middle schools
      participated. Parallel process growth mixture latent transition analysis was used
      to understand how trajectory profiles of middle school violence exposure was
      associated with high school bullying profiles. Impulsivity, depression, school
      belonging, and delinquency were assessed as moderators of the transition
      probabilities. A three class solution was found for violence exposure: decreasing
      parental violence/increasing community violence (n = 103; 6.4%), stable high
      parental violence and low community violence (n = 1,027; 63.7%), and increasing
      parental violence and stable high community violence (n = 481; 29.8%). Similarly,
      a three class solution was found for high school bullying: High Bullying
      Perpetration and High Victimization class (n = 259; 16%), Victimization only (n =
      1145; 71%), and low all class (n = 207; 13%). The largest proportion of youth
      transitioning into the high bullying and high victimization class were from the
      decreasing parental violence/increasing community violence. Depression,
      impulsivity, school belonging, and delinquency all had various moderating effects
      on transition probabilities. Our findings make it apparent that early forms of
      parental and community violence are associated with aggressive behaviors and
      experiences with victimization during high school. Prevention and intervention
      efforts should target individuals who display early and chronic patterns of
      exposure to violence as these individuals have the greatest risk of later
      aggressive and victimization in high school.

PMID- 30278117
TI  - Exogenous attention and memory for faces following contextual behavioral immune
      system activation.
AB  - The behavioral immune system (BIS) is characterized by affective, cognitive and
      behavioral processes that work in an articulated manner to prevent the occurrence
      of infections. Attention and memory evolved to enhance the organism's chances of
      survival and have been proposed to play an important role in the BIS. The present
      study investigated the effects of attention and memory for neutral faces after a
      contextual activation of the BIS. Participants were primed, by the use of film
      clips, either with infectious disease concerns or non-infectious disease
      concerns. They performed an exogenous attentional task involving the
      discrimination of target letters, with face stimuli presented as distractors,
      which was then followed by a surprise recognition task for the faces. The results
      showed that participants in the infectious disease condition were more accurate
      in the attentional task than participants in the control condition. No
      significant difference between groups was found in the response times during the
      attention task nor in memory performance. Overall, these results suggest that the
      BIS might be associated with a hypervigilant state towards cues in general and
      that BIS activation through this type of priming may not be sufficient to clearly
      activate mnemonic mechanisms.

PMID- 30278118
TI  - Cost-Effective Sampling and Analysis for Mycotoxins in a Cereal Batch.
AB  - The presence of hazards (e.g., contaminants, pathogens) in food/feed, water,
      plants, or animals can lead to major economic losses related to human and animal
      health or the rejection of batches of food or feed. Monitoring these hazards is
      important but can lead to high costs. This study aimed to find the most cost
      effective sampling and analysis (S&A) plan in the cases of the mycotoxins
      deoxynivalenol (DON) in a wheat batch and aflatoxins (AFB1 ) in a maize batch. An
      optimization model was constructed, maximizing the number of correct decisions
      for accepting/rejecting a batch of cereals, with a budget as major constraint.
      The decision variables were the choice of the analytical method: instrumental
      method (e.g., liquid chromatography combined with mass-spectrometry (LC-MS/MS)),
      enzyme-linked-immuno-assay (ELISA), or lateral flow devices (LFD), the number of
      incremental samples collected from the batch, and the number of aliquots
      analyzed. S&A plans using ELISA showed to be slightly more cost effective than
      S&A plans using the other two analytical methods. However, for DON in wheat, the
      difference between the optimal S&A plans using the three different analytical
      methods was minimal. For AFB1 in maize, the cost effectiveness of the S&A plan
      using instrumental methods or ELISA were comparable whereas the S&A plan
      considering onsite detection with LFDs was least cost effective. In case of
      nonofficial controls, which do not have to follow official regulations for
      sampling and analysis, onsite detection with ELISA for both AFB1 in maize and DON
      in wheat, or with LFDs for DON in wheat, could provide cost-effective
      alternatives.

PMID- 30278119
TI  - [Predicting Care and Repercussions for Caregivers of Surgical Patients at Home].
AB  - Objectives: To analyze the correlation between the state of health, knowledge,
      and social support of surgical patients' caregivers at home, with the intensity
      of nursing care and its consequences. Methods: A longitudinal observational study
      with follow-up at admission, discharge and 10 days following discharge at home,
      held in the surgical hospitalization unit at the Vic University Hospital,
      (Barcelona). A non-randomized and consecutive sample of 317 informal caregivers
      of surgical patients with abdominal surgery was included in the study. The
      characteristics of caregivers were studied using the Nursing Outcomes
      Classification indicators. The intensity of nursing care, consequences and impact
      on patient quality of life was evaluated through the validated ICUB97-R
      questionnaire. Results: Most of the caregivers were women, with an average age of
      52,9 +/- 13,7years, with no previous experience as caregivers. The greatest
      intensity of care and impact was observed on caregivers who attended dependent
      and/or cancer diagnosed patients at home, dedicating the largest time to provide
      care (p < 0,005). Predictor variables for the occurrence of consequences during
      convalescence at home were emotional health satisfaction, routine activity
      disruption, fear, sleep pattern and being a dependent patient. Conclusions:
      Emotional health satisfaction, routine activity disruption, fear, sleep pattern
      and being a dependent patient before surgery are strong predictive variables for
      the occurrence of consequences on caregivers during convalescence at home. There
      is a significant negative correlation between punctuations in the ICUB97-R
      questionnaire and the Nursing Outcomes Classification indicators.

PMID- 30278120
TI  - Force Field Parametrization from the Hirshfeld Molecular Electronic Density.
AB  - The Hirshfeld charges are linearly increased to reproduce the experimental
      dielectric constant of 10 polar solvents having values between 13 (pyridine) and
      182 ( N-methylformamide). The OPLS/AA force field is used to obtain the new
      parameters. The surface tension and liquid density are also target properties to
      determine the new nonbonding parameters. The charge scaling factor is between 1.2
      and 1.3. In addition, properties that were not used in the parametrization
      procedure, such as the heat of vaporization, self-diffusion coefficient, shear
      viscosity, isothermal compressibility, and volumetric expansion coefficient are
      obtained. Binary mixtures of amide/water and amide/amide are also studied. The
      original parameters of OPLS/AA, CGenFF, and GAFF force fields are evaluated. The
      TIP4P/epsilon force field is used to simulate water. The results from this work
      with the new parameters, for both pure components and binary mixtures, are in
      better agreement with experimental data than those obtained with the original
      values for most of the calculated properties. The maximum density of N
      methylformamide in aqueous solutions is correctly predicted only with the new
      parameters. The high value of the dielectric constant of acetamide, formamide,
      and N-methylformamide is discussed in terms of the chain formation from the
      hydrogen bond interactions.

PMID- 30278121
TI  - Unusually Strong Electrochemiluminescence from Iridium-Based Redox Polymers
      Immobilized As Thin Layers or Polymer Nanoparticles.
AB  - A new class of redox metallopolymer based on cyclometalated iridium(III) centers
      is described, with unusually intense luminescence properties in aqueous media. We
      report the facile synthesis, photophysical and electrochemical characterization,
      supported by DFT calculations and their electrochemiluminescence (ECL) properties
      which, under some circumstances, are significantly greater than the analogous
      ruthenium-based materials. The photoluminescence (PL) and ECL of these materials
      are further dramatically enhanced when dispersed or immobilized as polymeric
      nanoparticles (PNPs). This aggregation-induced emission (AIE and AIECL) operates
      by providing important protection for the cyclometalated iridium(III) centers
      against the types of quenching processes which commonly afflict iridium-based
      luminophores in aqueous media. The results suggest interesting new avenues of
      research for the application of such materials in and PL and ECL-based detection
      and imaging as well as light-emitting devices.

PMID- 30278122
TI  - Direct Electrochemical P(V) to P(III) Reduction of Phosphine Oxide Facilitated by
      Triaryl Borates.
AB  - Triaryl borate Lewis acids facilitate the direct two-electron reduction of the
      P(V) center of triphenylphosphine oxide (TPPO) to the P(III) center of
      triphenylphosphine at faradaic efficiencies of 37%. Insight from direct P(V) to
      P(III) reduction is provided from cyclic voltammetry. The electrochemical
      reduction of TPPO proceeds through an unusual ECrECi mechanism in which the
      breaking of the phosphoryl bond in a two-electron-reduced association complex
      with the triaryl borate is rate-determining. The rate and faradaic efficiency for
      TPPO reduction are tuned by judicious choice of substituents on triaryl borate,
      with tris(4-methoxyphenyl) borate demonstrating the highest for both. These
      results suggest that an attractive route toward the room-temperature reduction of
      phosphate for phosphorus reclamation is greatly facilitated by the stabilization
      of reduced phosphate intermediates through their association with Lewis acids.

PMID- 30278123
TI  - Catch and Release Photosensitizers: Combining Dual-Action Ruthenium Complexes
      with Protease Inactivation for Targeting Invasive Cancers.
AB  - Dual action agents containing a cysteine protease inhibitor and Ru-based
      photosensitizer for photodynamic therapy (PDT) were designed, synthesized, and
      validated in 2D culture and 3D functional imaging assays of triple-negative human
      breast cancer (TNBC). These combination agents deliver and release Ru-based PDT
      agents to tumor cells and cause cancer cell death upon irradiation with visible
      light, while at the same time inactivating cathespin B (CTSB), a cysteine
      protease strongly associated with invasive and metastatic behavior. In total five
      Ru-based complexes were synthesized with the formula [Ru(bpy)2(1)](O2CCF3)2 (3),
      where bpy = 2,2'-bipyridine and 1 = a bipyridine-based epoxysuccinyl inhibitor;
      [Ru(tpy)(NN)(2)](PF6)2, where tpy = terpiridine, 2 = a pyridine-based
      epoxysuccinyl inhibitor and NN = 2,2'-bipyridine (4); 6,6'-dimethyl-2,2'
      bipyridine (5); benzo[ i]dipyrido[3,2- a:2',3'- c]phenazine (6); and 3,6
      dimethylbenzo[ i]dipyrido[3,2- a:2',3'- c]phenazine (7). Compound 3 contains a
      [Ru(bpy)3]2+ fluorophore and was designed to track the subcellular localization
      of the conjugates, whereas compounds 4-7 were designed to undergo either
      photoactivated ligand dissociation and/or singlet oxygen generation.
      Photochemical studies confirmed that complexes 5 and 7 undergo photoactivated
      ligand dissociation, whereas 6 and 7 generate singlet oxygen. Inhibitors 1-7 all
      potently and irreversibly inhibit CTSB. Compounds 4-7 were evaluated against MDA
      MB-231 TNBC and MCF-10A breast epithelial cells in 2D and 3D culture for effects
      on proteolysis and cell viability under dark and light conditions. Collectively,
      these data reveal that 4-7 potently inhibit dye-quenched (DQ) collagen
      degradation, whereas only compound 7 causes efficient cell death under light
      conditions, consistent with its ability to release a Ru(II)-based photosensitizer
      and to also generate 1O2.

PMID- 30278124
TI  - Computation of Dynamic Polarizabilities and van der Waals Coefficients from Path
      Integral Monte Carlo.
AB  - We demonstrate computation of total dynamic multipole polarizabilities using path
      integral Monte Carlo method (PIMC). The PIMC approach enables accurate thermal
      and nonadiabatic mixing of electronic, rotational, and vibrational degrees of
      freedom. Therefore, we can study the thermal effects, or lack thereof, in the
      full multipole spectra of the chosen one- and two-electron systems: H, Ps, He,
      Ps2, H2, and HD+. We first compute multipole-multipole correlation functions up
      to octupole order in imaginary time. The real-domain spectral function is then
      obtained by analytical continuation with the maximum entropy method. In general,
      sharpness of the active spectra is limited, but the obtained off-resonant
      polarizabilities are in good agreement with the existing literature. Several weak
      and strong thermal effects are observed. Furthermore, the polarizabilities of Ps2
      and some higher multipole and higher frequency data have not been published
      before. In addition, we compute isotropic dispersion coefficients C6, C8, and C10
      between pairs of species using the simplified Casimir-Polder formulas.

PMID- 30278126
TI  - Functional Analyses of Cassette Chromosome Recombinase C2 (CcrC2) and Its Use in
      Eliminating Methicillin Resistance by Combining CRISPR-Cas9.
AB  - Worldwide occurrence of methicillin-resistant Staphylococcus aureus (MRSA) poses
      enormous challenges for both communities and health care settings. Cassette
      chromosome recombinases (Ccr) specifically perform excision and acquisition of a
      staphylococcal cassette chromosome mec (SCC mec) in staphylococci and are
      responsible for the spread of methicillin resistance. This study explored the
      roles of CcrC2, a recently discovered Ccr, in the horizontal transfer of SCC mec
      and developed a potential means to control the spread of methicillin resistance.
      Knockout of CcrC2 completely aborted the excision of SCC mec, while
      overexpression of CcrC2 partially removed the SCC mec from the genome and
      transformed methicillin-resistant Staphylococcus aureus (MRSA) into methicillin
      susceptible Staphylococcus aureus (MSSA). Moreover, two nucleotide residues
      (G5C6) in the direct repeat sequence within an att site were found to be critical
      for excision and acquisition efficiencies. To block the horizontal transfer of
      methicillin resistance, a SCC mec killer system was developed by combining the
      CcrC2-mediated SCC mec excision and the mecA-targeting CRISPR-Cas9 machinery. The
      SCC mec killer transformed MRSA to MSSA and disrupted the mecA-carrying SCC mec
      intermediate, thereby eliminating methicillin resistance determinant mecA gene
      inside a MRSA cell and blocking the horizontal transfer of SCC mec. The SCC mec
      killer was versatile for efficiently removing multiple types of SCC mec elements.
      It is envisioned that this approach could offer a new means to control the spread
      of methicillin resistance.

PMID- 30278125
TI  - Co-opting the Lap System of Pseudomonas fluorescens To Reversibly Customize
      Bacterial Cell Surfaces.
AB  - Initial attachment to a surface is a key and highly regulated step in biofilm
      formation. In this study, we present a platform for reversibly functionalizing
      bacterial cell surfaces with an emphasis on designing biofilms. We engineered the
      Lap system of Pseudomonas fluorescens Pf0-1, which is normally used to regulate
      initial cell surface attachment, to display various protein cargo at the
      bacterial cell surface and control extracellular release of the cargo in response
      to changing levels of the second messenger c-di-GMP. To accomplish this goal, we
      fused the protein cargo between the N-terminal retention module and C-terminal
      secretion signal of LapA and controlled surface localization of the cargo with
      natural signals known to stimulate or deplete c-di-GMP levels in P. fluorescens
      Pf0-1. We show this system can tolerate large cargo in excess of 500 amino acids,
      direct P. fluorescens Pf0-1 to surfaces it does not typically colonize, and
      program this microbe to sequester the toxic medal cadmium.

PMID- 30278128
TI  - FINDSITEcomb2.0: A New Approach for Virtual Ligand Screening of Proteins and
      Virtual Target Screening of Biomolecules.
AB  - Computational approaches for predicting protein-ligand interactions can
      facilitate drug lead discovery and drug target determination. We have previously
      developed a threading/structural-based approach, FINDSITEcomb, for the virtual
      ligand screening of proteins that has been extensively experimentally validated.
      Even when low resolution predicted protein structures are employed, FINDSITEcomb
      has the advantage of being faster and more accurate than traditional high
      resolution structure-based docking methods. It also overcomes the limitations of
      traditional QSAR methods that require a known set of seed ligands that bind to
      the given protein target. Here, we further improve FINDSITEcomb by enhancing its
      template ligand selection from the PDB/DrugBank/ChEMBL libraries of known protein
      ligand interactions by (1) parsing the template proteins and their corresponding
      binding ligands in the DrugBank and ChEMBL libraries into domains so that the
      ligands with falsely matched domains to the targets will not be selected as
      template ligands; (2) applying various thresholds to filter out falsely matched
      template structures in the structure comparison process and thus their
      corresponding ligands for template ligand selection. With a sequence identity
      cutoff of 30% of target to templates and modeled target structures,
      FINDSITEcomb2.0 is shown to significantly improve upon FINDSITEcomb on the DUD-E
      benchmark set by increasing the 1% enrichment factor from 16.7 to 22.1, with a p
      value of 4.3 * 10-3 by the Student t-test. With an 80% sequence identity cutoff
      of target to templates for the DUD-E set and modeled target structures,
      FINDSITEcomb2.0, having a 1% ROC enrichment factor of 52.39, also outperforms
      state-of-the-art methods that employ machine learning such as a deep
      convolutional neural network, CNN, with an enrichment of 29.65. Thus,
      FINDSITEcomb2.0 represents a significant improvement in the state-of-the-art. The
      FINDSITEcomb2.0 web service is freely available for academic users at
      http://pwp.gatech.edu/cssb/FINDSITE-COMB-2 .

PMID- 30278127
TI  - Hierarchical GeP5/Carbon Nanocomposite with Dual-Carbon Conductive Network as
      Promising Anode Material for Sodium-Ion Batteries.
AB  - Due to the Earth's scarcity of lithium, replacing lithium with earth-abundant and
      low-cost sodium for sodium-ion batteries (SIBs) has recently become a promising
      substitute for lithium-ion batteries. However, the shortage of appropriate anode
      materials limits the development of SIBs. Here, a dual-carbon conductive network
      enhanced GeP5 (GeP5/acetylene black/partially reduced graphene oxide sheets
      (GeP5/AB/p-rGO)) composite is successfully prepared by a facile ball milling
      method. The dual-carbon network not only provides more transport pathways for
      electrons but also relaxes the huge volume change of the electrode material
      during the charge/discharge process. Compared with only AB- or GO-modified GeP5
      (GeP5/AB or GeP5/GO) composite, the GeP5/AB/p-rGO composite shows a superior
      sodium storage performance with an excellent rate and cycle performance. It
      delivers a high reversible capacity of 597.5 and 175 mAh/g at the current density
      of 0.1 and 5.0 A/g, respectively. Furthermore, at the current density of 0.5 A/g,
      the GeP5/AB/p-rGO composite shows the reversible capacity of 400 mAh/g after 50
      cycles with a little capacity attenuation. All above results prove that the
      GeP5/AB/p-rGO composite has a good prospect of application as an anode material
      for SIBs.

PMID- 30278130
TI  - Cavity Ring-Down Absorption Spectroscopy: Optical Characterization of ICl Product
      in Photodissociation of CH2ICl at 248 nm.
AB  - Iodine monochloride (ICl) elimination from one-photon dissociation of CH2ICl at
      248 nm is monitored by cavity ring-down absorption spectroscopy (CRDS). The
      spectrum of ICl is acquired in the transition of B3Pi0 <- X1Sigma+ and is
      confirmed to result from a primary photodissociation, that is, CH2ICl + hnu ->
      CH2 + ICl. The vibrational population ratio is determined with the aid of
      spectral simulation to be 1:(0.36 +/- 0.10):(0.11 +/- 0.05) for the vibrational
      levels nu = 0, 1, and 2 in the ground electronic state, corresponding to a
      Boltzmann-like vibrational temperature of 535 +/- 69 K. The quantum yield of the
      ICl molecular channel for the reaction is obtained to be 0.052 +/- 0.026 using a
      relative method in which the scheme CH2Br2 -> CH2 + Br2 is adopted as the
      reference reaction. The ICl product contributed by the secondary collisions is
      minimized such that its quantum yield obtained is not overestimated. With the aid
      of the CCSD(T)//B3LYP/MIDI! level of theory, the ICl elimination from CH2ICl is
      evaluated to follow three pathways via either (1) a three-center transition state
      or (2) two isomerization transition states. However, the three-center concerted
      mechanism is verified to be unfavorable.

PMID- 30278129
TI  - Modular Pore-Forming Immunotoxins with Caged Cytotoxicity Tailored by Directed
      Evolution.
AB  - Immunotoxins are proteins containing a cell-targeting element linked to a toxin
      that are under investigation for next-generation cancer treatment. However, these
      agents are difficult to synthesize, chemically heterogeneous, expensive, and show
      toxicity toward healthy cells. In this work, we describe the synthesis and
      characterization of a new type of immunotoxin that showed exquisite selectivity
      toward targeted cells. In our construct, targeting molecules were covalently
      attached or genetically fused to oligomeric pore-forming toxins. The activity of
      the immunotoxin was then caged by fusing a soluble protein to the transmembrane
      domain and activated via cleavage with furin, which is a protease that is
      overexpressed in many cancer cells. During the several coupling steps, directed
      evolution allowed the efficient synthesis of the molecules in E. coli cells, as
      well as selection for further specificity toward targeted cells. The final
      construct showed no off-target activity, while acquiring an additional degree of
      specificity toward the targeted cells upon activation. The pore-forming toxins
      described here do not require internalization to operate, while the many
      protomeric subunits can be individually modified to refine target specificity.

PMID- 30278131
TI  - [99mTc][Tc(N)PNP43]-Labeled RGD Peptides As New Probes for a Selective Detection
      of alphavbeta3 Integrin: Synthesis, Structure-Activity and Pharmacokinetic
      Studies.
AB  - New integrin-selective molecules suitable for therapeutic or imaging purposes are
      currently of interest in development of effective personalized medical platforms.
      RGDechi is a bifunctional peptide selective for integrin alphavbeta3. Herein,
      RGDechi and three truncated derivatives functionalized with a cysteine (1-4) were
      synthesized and labeled with the [99mTc][Tc(N)PNP43]-synthon ([PNP43 =
      (CH3)2P(CH2)2N(C2H4OCH3)(CH2)2P(CH3)2]) (99mTc1-4) as a basis for selective
      integrin recognition. The pharmacological parameters of all radiolabeled peptides
      were assessed along with the pharmacokinetic profiles of the most promising
      99mTc1 and 99mTc2 compounds both on healthy and melanoma-bearing mice. Their
      metabolism and metabolite identification are also reported. 99mTc1-2 are able to
      discriminate between endogenously expressed integrins alphavbeta3 and alphavbeta5
      and possess favorable pharmacokinetics characterized by low liver uptake and
      rapid elimination from nontarget tissues resulting in positive target-to
      nontarget ratios. Results are encouraging; the presented construct can be
      considered the starting point for the development of agents for the selective
      detection of alphavbeta3 expression by SPECT.

PMID- 30278132
TI  - Discerning Chemical Pressure amidst Weak Potentials: Vibrational Modes and
      Dumbbell/Atom Substitution in Intermetallic Aluminides.
AB  - The space requirements of atoms are generally regarded as key constraints in the
      structures, reactivity, and physical properties of chemical systems. However, the
      empirical nature of such considerations renders the elucidation of these size
      effects with first-principles calculations challenging. DFT-chemical pressure
      (DFT-CP) analysis, in which the output of DFT calculations is used to construct
      maps of the local pressures acting between atoms due to lattice constraints, is
      one productive approach to extracting the role of atomic size in the crystal
      structures of materials. While in principle this method should be applicable to
      any system for which DFT is deemed an appropriate treatment, so far it has worked
      most successfully when semicore electrons are included in the valence set of each
      atom to supply an explicit repulsive response to compression. In this Article, we
      address this limiting factor, using as model systems intermetallics based on
      aluminum, a key component in many structurally interesting phases that is not
      amenable to modeling with a semicore pseudopotential. Beginning with the Laves
      phase CaAl2, we illustrate the difficulties of creating a CP scheme that reflects
      the compound's phonon band structure with the original method due to minimal core
      responses on the Al atoms. These deficiencies are resolved through a spatial
      mapping of three energetic terms that were previously treated as homogeneous
      background effects: the Ewald, Ealpha, and nonlocal pseudopotential components.
      When charge transfer is factored into the integration scheme, CP schemes
      consistent with the phonon band structure are obtainable for CaAl2, regardless of
      whether Ca is modeled with a semicore or valence-only pseudopotential. Finally,
      we demonstrate the utility of the revised method through its application to the
      La3Al11 structure, which is shown to soothe CPs that would be encountered in a
      hypothetical BaAl4-type parent phase through the substitution of selected Al2
      pairs with single Al atoms. La3Al11 then emerges as an example of a more general
      phenomenon, CP-driven substitutions of simple motifs.

PMID- 30278133
TI  - Bisulfite-Free, Nanoscale Analysis of 5-Hydroxymethylcytosine at Single Base
      Resolution.
AB  - High-resolution detection of genome-wide 5-hydroxymethylcytosine (5hmC) sites of
      small-scale samples remains challenging. Here, we present hmC-CATCH, a bisulfite
      free, base-resolution method for the genome-wide detection of 5hmC. hmC-CATCH is
      based on selective 5hmC oxidation, chemical labeling and subsequent C-to-T
      transition during PCR. Requiring only nanoscale input genomic DNA samples, hmC
      CATCH enabled us to detect genome-wide hydroxymethylome of human embryonic stem
      cells in a cost-effective manner. Further application of hmC-CATCH to cell-free
      DNA (cfDNA) of healthy donors and cancer patients revealed base-resolution
      hydroxymethylome in the human cfDNA for the first time. We anticipate that our
      chemical biology approach will find broad applications in hydroxymethylome
      analysis of limited biological and clinical samples.

PMID- 30278134
TI  - Dynamics of Dimethylbutanols in Plastic Crystalline Phases by Field Cycling 1H
      NMR Relaxometry.
AB  - 2,2-Dimethylbutan-1-ol (2,2-DM-1-B), 3,3-dimethylbutan-1-ol (3,3-DM-1-B), and 3,3
      dimethylbutan-2-ol (3,3-DM-2-B) show a rich solid-state polymorphism, which
      includes one or more plastic crystalline phases (also referred to as
      orientationally disordered crystalline (ODIC) phases) and glass of the liquid or
      ODIC phases. In this work, the dynamics of the three isomeric alcohols was
      investigated in the liquid and plastic crystalline phases by fast field cycling
      1H NMR relaxometry in the temperature range between 213 and 303 K. The analysis
      of the nuclear magnetic relaxation dispersion curves (i.e., longitudinal
      relaxation rate R1 vs 1H Larmor frequency) acquired for the different alcohols at
      different temperatures gave quantitative information on internal motions, overall
      molecular reorientations, and molecular self-diffusion. Self-diffusion
      coefficients were also determined in the liquid phase and in some ODIC phases of
      the samples from the trends of 1H R1 as a function of the frequency square root
      at low frequencies. Remarkable changes in the temperature trends of correlation
      times and self-diffusion coefficients were found at the transition between the
      liquid and the ODIC phase for 2,2-DM-1-B and 3,3-DM-1-B, and between ODIC phases
      for 3,3-DM-2-B, the latter sample showing a markedly different dynamic and phase
      behavior.

PMID- 30278135
TI  - Grand Canonical Monte Carlo Simulations on Phase Equilibria of Methane, Carbon
      Dioxide, and Their Mixture Hydrates.
AB  - The cage occupancy plays a crucial role in the thermodynamic stability of
      clathrate hydrates and is an important quantity for understanding the CO2-CH4
      replacement phenomenon. In this work, the occupancy isotherms of pure CH4, pure
      CO2, and their mixture in sI and sII hydrates are studied by GCMC + MD
      simulations. The adsorption of CH4 and CO2 + CH4 in the sI and sII hydrates can
      be categorized as the one-site Langmuir type. The calculated occupancy ratio
      thetaL/thetaS and the abundance ratio of CO2 to CH4 vary with the temperature and
      pressure, which provide the prerequisite information for the prediction of CH4
      recovery yield at different conditions in the CO2-CH4 gas exchange process. The
      phase equilibria of clathrate hydrates of pure gases and mixtures are explored
      and the corresponding heat of dissociation and hydration numbers are determined.
      The current investigation provides new perspectives to understand the mechanism
      behind the gas adsorption behavior of clathrate hydrates.

PMID- 30278136
TI  - Electrochemically Triggered Surface Deposition of Polyelectrolytes.
AB  - An electrochemical approach to surface deposition of polyelectrolytes on self
      assembled monolayers is presented. This deposition process can be triggered
      facilely by a potential bias, which oxidizes ferrocene moieties included in the
      self-assembled monolayer to ferrocenium, whose charge compensation is fulfilled
      by polyelectrolytes and associated counterions. This approach is quite general,
      affording quantitative deposition of both polyanions and polycations with a wide
      range of chemical identities (synthetic polymers, peptides, and DNA) and
      molecular weights (103-107 Da as tested). Conventional layer-by-layer
      polyelectrolyte deposition can be straightforwardly combined with this method to
      produce electroactive polymer films. Several techniques, including voltammetry,
      fluorescence spectroscopy, contact angle analysis, electrochemical quartz crystal
      microbalance, and atomic force microscopy, were employed to characterize the
      deposition processes. A detailed discussion on the involved deposition mechanisms
      is also presented.

PMID- 30278137
TI  - Artificial Phospholipids and Their Vesicles.
AB  - Phospholipids are at the heart and origin of life on this planet. The
      possibilities in terms of phospholipid self-assembly and biological functions
      seem limitless. Nonetheless, nature exploits only a small fraction of the
      available chemical space of phospholipids. Using chemical synthesis, artificial
      phospholipid structures become accessible, and the study of their biophysics may
      reveal unprecedented properties. In this article, the recent advances by our work
      group in the field of chemical lipidology are summarized. The family of
      diamidophospholipids is discussed in detail from monolayer characterization to
      the formation of faceted vesicles, culminating in the template-free self-assembly
      of phospholipid cubes and the possible applications of vesicle origami in modern
      personalized medicine.

PMID- 30278138
TI  - Enhanced Charging-Induced Resistance Variations of Nanoporous Gold by Dealloying
      in Neutral Silver Nitrate Solution.
AB  - Nanoporous gold (np-Au), produced by dealloying in silver nitrate solution
      exhibits extraordinary high surface-to-volume ratios of more than 20 m2/g which
      represents an excellent prerequisite for property tuning by surface charging.
      Upon electrochemical charging in aqueous KOH solution, the electrical resistance
      is observed to vary reversibly by up to 88%. The charge coefficient, thus the
      sensitivity of the resistance toward the imposed charge per mol, is however
      significantly smaller compared to conventionally prepared np-Au, etched in nitric
      acid solution. While the strong resistance variation observed in the present work
      can directly be related to the high charge transfer due to extraordinary fine
      porosity, the charge coefficients can be understood with regards to the matrix
      resistance of the respective materials, which is strongly influenced by
      dealloying residuals.

PMID- 30278139
TI  - Oxidative Layer-By-Layer Multilayers Based on Metal Coordination: Influence of
      Intervening Graphene Oxide Layers.
AB  - Layer-by-layer (LbL) fabricated oxidative multilayers consisting of successive
      layers of inorganic polyphosphate (PP) and Ce(IV) can electrolessly form thin
      conducting polymer films on their surface. We describe the effect of substituting
      every second PP layer in the (PP/Ce) multilayers for graphene oxide (GO) as a
      means of modifying the structure and mechanical properties of these (GO/Ce/PP/Ce)
      films and enhancing their growth. Both types of LbL films are based on reversible
      coordinative bonding between the metal ions and the oxygen-bearing groups in PP
      and GO, instead of purely electrostatic interactions. The GO incorporation leads
      to the doubling of the areal mass density and to a dry film thickness close to
      300 nm after 4 (GO/Ce/PP/Ce) tetralayers. The film roughness increases
      significantly with thickness. The (PP/Ce) films are soft materials with
      approximately equal shear storage and loss moduli, but the incorporation of GO
      doubles the storage modulus. PP displays a marked terminating layer effect and
      practically eliminates mechanical losses, making the (GO/Ce/PP/Ce) films almost
      pure soft elastomers. The smoothness of the (PP/Ce) films and the PP-termination
      effects are attributed to the reversible coordinative bonding. The (GO/Ce/PP/Ce)
      films oxidize pyrrole and 3,4-ethylenedioxythiophene (EDOT) and form polypyrrole
      and PEDOT films on their surfaces. These polymer films are considerably thicker
      than those formed using the (PP/Ce) multilayers with the same nominal amount of
      cerium layers. The GO sheets interfere with the polymerization reaction and make
      its kinetics biphasic. The (GO/Ce) multilayers without PP are brittle and thin.

PMID- 30278141
TI  - Chemically Resistant Perfluoroalkoxy Nanoparticle-Packed Porous Substrates and
      Their Use in Colorimetric Sensor Arrays.
AB  - To create printing substrates for colorimetric sensor arrays, chemically
      resistant membranes are prepared by coating cellulose filter paper with
      perfluoroalkoxy (PFA) polymer nanoparticles. A water-based fluorothermoplastic
      polymer dispersion was diluted with an organic solvent that causes weak
      aggregation of polymer nanoparticles. The resulting solution improved adhesion
      between the polymer and the cellulose membrane, providing a more mechanically
      stable substrate. These PFA polymer-coated substrates demonstrated superior
      chemical resistance against strong alkalines and had relatively uniform
      nanoporous structures that substantially improved the printability of a
      colorimetric sensor array. Finally, colorimetric sensor arrays printed on these
      substrates were evaluated for the detection of four different toxic industrial
      chemicals (e.g., ammonia, hydrogen sulfide, nitrogen dioxide, and sulfur dioxide)
      at or below their permissible exposure limits.

PMID- 30278140
TI  - Splash-Resistant and Light-Weight Silk-Sheathed Wires for Textile Electronics.
AB  - Silk has outstanding mechanical properties and biocompatibility. It has been used
      to fabricate traditional textiles for thousands of years and can be produced in
      large scale. Silk materials are potentially attractive in modern textile
      electronics. However, silk is not electrically conductive, thus limiting its
      applications in electronics. Moreover, regenerated silk is generally rigid and
      brittle, which hinder post processing. Here we report the fabrication of
      conductive silk wire in which carbon nanotube (CNT) yarns are wrapped with fluffy
      and flexible silk nanofiber films. The silk nanofiber film was prepared by
      electrospinning and then wrapped around a rotating CNT yarn in situ. The obtained
      silk-sheathed CNT (CNT@Silk) wire has an insulating sheath, which protects the
      body against electrical shock. In addition, the fabricated wires exhibit a high
      electrical conductivity (3.1 * 104 S/m), good mechanical strength (16 cN/tex),
      excellent flexibility, and high durability. More importantly, the wires have an
      extremely low density (2.0-7.8 * 104 g/m3), which is 2 orders of magnitude lower
      than that of the traditional metal wire (for example, Cu). Moreover, the wires
      display a good resistance to humidity, and a simple post treatment can make the
      wires splash-resistant, thereby expanding its applications. On the basis of these
      features, we demonstrate the use of the lightweight CNT@Silk wires in smart
      clothes, including electrochromism and near-field communication.

PMID- 30278142
TI  - Alveolar Epithelial Cells Burn Fat to Survive Acute Lung Injury.

PMID- 30278143
TI  - Overcoming Health Literacy Barriers to Improve Asthma Inhaler Therapy Adherence.

PMID- 30278144
TI  - Reply to: Extent of Overuse of Inhaled Corticosteroids in Chronic Obstructive
      Pulmonary Disease.

PMID- 30278145
TI  - DNA barcoding of forensically important flies in the Western Cape, South Africa.
AB  - Forensic entomology aids the determination of post mortem interval based on
      arthropods associated with a deceased body. This relies on the accurate
      identification of insects that visit the body, particularly first colonisers such
      as Calliphoridae (Diptera). Traditional species identification though
      morphological keys can be challenging as immature or closely related specimens
      can look similar. Some of these challenges have been overcome through "DNA
      barcoding", which involves the sequencing of informative regions within a
      species' DNA and comparison to a database of reference sequences. However,
      reference DNA sequences of blow fly species in South Africa is currently limited.
      In this study, adult blow flies representing four species common to the Western
      Cape, South Africa (Chrysomya chloropyga, Chrysomya albiceps, Chrysomya
      marginalis, Lucilia sericata) were examined using morphological keys and DNA
      barcoding of two regions: COI and ITS2. These DNA sequences were then used as
      references for the successful identification of seven unknown immature specimens.
      Intraspecific divergence showed a maximum of 0.36% and 2.25% for COI and ITS2,
      respectively; interspecific divergence showed a minimum of 6.14% and 64.6% for
      COI and ITS2, respectively. According to these results, COI and ITS2 have
      sufficient discriminatory power for species-level identification for the four
      species studied.

PMID- 30278146
TI  - Restrictions on drugs with medical value: Moving beyond stalemate.

PMID- 30278148
TI  - Considerations for incorporating real-time PCR assays into routine marine
      biosecurity surveillance programmes: a case study targeting the Mediterranean
      fanworm (Sabella spallanzanii) and club tunicate (Styela clava).
AB  - Molecular techniques may provide effective tools to enhance marine biosecurity
      surveillance. Prior to routine implementation, evidence-based consideration of
      their benefits and limitations is needed. In this study, we assessed the
      efficiency and practicality of visual diver surveys and real-time PCR assays
      (targeting DNA and RNA) for detecting two marine invasive species whose
      infestation levels varied between species and location: Sabella spallanzanii and
      Styela clava. Filtered water samples (n = 171) were collected in parallel with
      dive surveys at two locations as part of the New Zealand Marine High Risk Site
      Surveillance programme: Nelson Harbour (27 sites) and Waitemata Harbour (30
      sites). Diver surveys resulted in a greater number of detections compared to real
      time PCR: S. clava - 21 versus 5 sites in Nelson, 6 versus 1 in Auckland; S.
      spallanzanii - 18 versus 10 in Auckland, no detections in Nelson. Occupancy
      modelling derived detection probabilities for the real-time PCR for S. clava were
      low (14%), compared to S. spallanzanii (66%). This could be related to
      abundances, or species-specific differences in DNA shedding. Only one RNA sample
      was positive, suggesting that most detections were from extracellular DNA or non
      viable fragments. While molecular methods cannot yet replace visual observations,
      this study shows they provide useful complementary information.

PMID- 30278147
TI  - Characterization and comparison of poorly known moth communities through DNA
      barcoding in two Afrotropical environments in Gabon.
AB  - Biodiversity research in tropical ecosystems-popularized as the most biodiverse
      habitats on Earth-often neglects invertebrates, yet invertebrates represent the
      bulk of local species richness. Insect communities in particular remain strongly
      impeded by both Linnaean and Wallacean shortfalls, and identifying species often
      remains a formidable challenge inhibiting the use of these organisms as
      indicators for ecological and conservation studies. Here we use DNA barcoding as
      an alternative to the traditional taxonomic approach for characterizing and
      comparing the diversity of moth communities in two different ecosystems in Gabon.
      Though sampling remains very incomplete, as evidenced by the high proportion
      (59%) of species represented by singletons, our results reveal an outstanding
      diversity. With about 3500 specimens sequenced and representing 1385 BINs
      (Barcode Index Numbers, used as a proxy to species) in 23 families, the diversity
      of moths in the two sites sampled is higher than the current number of species
      listed for the entire country, highlighting the huge gap in biodiversity
      knowledge for this country. Both seasonal and spatial turnovers are strikingly
      high (18.3% of BINs shared between seasons, and 13.3% between sites) and draw
      attention to the need to account for these when running regional surveys. Our
      results also highlight the richness and singularity of savannah environments and
      emphasize the status of Central African ecosystems as hotspots of biodiversity.

PMID- 30278149
TI  - Extent of Overuse of Inhaled Corticosteroids in Chronic Obstructive Pulmonary
      Disease.

PMID- 30278151
TI  - Biological effect and molecular docking of anticancer palladium and platinum
      complexes with morpholine dithiocarbamate on human serum albumin as a blood
      carrier protein.
AB  - The aim of this study was to examine the interaction of [Pd(2,2'-bipyridine)
      (morpholinedithiocarbamate)]NO3 and [Pt (2,2'
      bipyridine)(morpholinedithiocarbamate)]NO3 with human serum albumin under
      physiological conditions by using fluorescence, absorption, and circular
      dichroism spectroscopic techniques. Spectroscopic analysis of the emission
      quenching at different temperatures demonstrated that the quenching mechanism was
      static quenching. From the circular dichroism results, thermal stability study,
      it was found that the interaction of the complexes with human serum albumin
      caused a conformational change of the protein reversibly. These 2 anticancer Pd
      and Pt complexes were activated against chronic myelogenous leukemia cell line
      K562, so that 50% cytotoxic concentration values of 16 and 26 MUM for Pd and Pt
      complexes, respectively, were observed, which were much lower than that of
      cisplatin (154 MUM). Biological activities of both Pd and Pt complexes were also
      assayed against selective microorganisms by the disc diffusion method. These
      results showed that the Pd(II) complex is antifungal agent but Pt(II) complex has
      antibacterial activity. Also, the interaction of both metal derivative complexes
      was studied by molecular docking. Complementary molecular docking results may be
      useful to determine the binding mechanism of human serum albumin in
      pharmaceutical and biophysical studies providing new insight in the novel
      pharmacology.

PMID- 30278150
TI  - A Commentary on Maternal Smoking During Pregnancy: The Story Behind the Trends.

PMID- 30278152
TI  - The modified IVAN technique: Hard and soft tissue augmentation at extraction for
      delayed implant placement.
AB  - Failure of a natural tooth may not permit placement of an implant at the time of
      extraction due to insufficiency in available bone to house the implant.
      Reconstruction of the extraction socket frequently involves both hard and soft
      tissue augmentation to provide a site that can house the implant and ridge
      contours that mimic the adjacent natural anatomy. The modified IVAN technique
      achieves those goals and may be used in both delayed and immediate placement
      situations. A case will be presented showing use of the mIVAN technique with a
      delayed implant placement and long-term follow-up demonstrating hard and soft
      tissue maintenance.

PMID- 30278153
TI  - Striving to Meet Healthy People 2020 Objectives: Trend Analysis of Maternal
      Smoking.
AB  - OBJECTIVES:: We examined trends in prevalence rates of smoking and smoking
      cessation during pregnancy among women in the United States to assess achievement
      of Healthy People 2020 prevention targets. METHODS:: We assessed the smoking
      habits of 30 667 mothers whose children were born between 1985 and 2014 and who
      were sampled by the National Health and Nutrition Examination Survey, 1999-2014.
      Sampled participants were children aged 0-15 at the time of interview; however,
      an adult proxy-usually the biological mother-responded on the child's behalf and
      reported information about maternal tobacco use during pregnancy. We calculated
      prevalence rates, adjusted odds ratios (aORs), and predicted annual increase or
      decrease of smoking and quitting smoking during pregnancy, adjusting for mother's
      age at delivery and income level and child's race/ethnicity and sex. RESULTS::
      The average annual prevalence of smoking at any time during pregnancy decreased
      from 25.7% (95% confidence interval [CI], 15.3%-36.0%) in 1985 to 10.1% (95% CI,
      7.1%-13.0%) in 2014 ( P < .001), and quitting smoking at any time during the
      index pregnancy increased from 36.6% (95% CI, 20.3%-52.9%) in 1985 to 54.9% (95%
      CI, 44.4%-65.4%) in 2008 ( P = .002). The adjusted annual risk of smoking during
      pregnancy decreased significantly by 3% (aOR = 0.97; 95% CI, 0.95-0.98; P <
      .001). The prevalence rate of smoking in the year 2020 extrapolated from the
      current trend would be 6.1%. CONCLUSIONS:: Smoking during pregnancy in the United
      States is declining. However, renewed public health measures are needed to
      achieve the Healthy People 2020 objectives of preventing smoking among pregnant
      women in the United States.

PMID- 30278154
TI  - Molecular characterization of human echinococcosis in Sichuan, Western China.
AB  - Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are highly co-endemic
      in Sichuan, a part of Qinghai-Tibet Plateau where is a typical Tibetan nomadic
      community living area. In order to better understand the Echinococcus spp. of
      human being infected origins in this area, 140 lesions were collected from
      echinococcosis patients who were received operations during the period of 2014
      2016 in different geographic districts in this region. Partial DNA sequences of
      the mitochondrial cox1 gene were analyzed. The genetic characterization of the
      isolates from 3 different places including Ganzi, Aba and Liangshan were
      assessed. Of all the 140 samples, the great majority was identified as
      Echinococcus granulosus sensu stricto (n = 108). Echinococcus multilocularis was
      confirmed to be another important pathogen of the human infections (n = 31).
      Additionally, one Echinococcus canadensis (G6/7) isolate from Ganzi was
      confirmed. Comparing the clinical diagnosis with the sequencing results, 6.4%
      (9/140) of the cases were misdiagnosed between AE and CE, and another 8.6%
      (12/140) were unclassified to sub-type in echinococcosis. Higher rates of
      misdiagnosis and unclassified diagnosis were found in AE cases (12.9%, 4/31 and
      16.1%, 5/31 respectively) compared to CE (4.6%, 5/109 and 6.4%, 7/109
      respectively). In E.granulosus s.s., a total of 34 haplotypes were detected, and
      4 haplotypes were inferred from E.multilocularis. The haplotype networks of the 2
      species exhibited a similar star-shaped feature with a dominant haplotype in the
      center. Geographically specific haplotypes were observed in Ganzi and Aba
      respectively. This study provides insight into the current species causing human
      echinococcosis in the Tibetan districts of Sichuan. E.granulosus s.s. and
      E.multilocularis are confirmed to be the main causative agents, and the existence
      of E.canadensis (G6/7) is also observed in the region. Molecular diagnosis was
      proven to be essential for the confirmation of human echinococcosis in the area.

PMID- 30278155
TI  - A novel solution phase PAI-1/uPA-biotin complex assay for the measurement of
      active PAI-1 in plasma.
AB  - We devised a new assay procedure to use biotinylated uPA to trace the active PAI
      1 levels in the plasma. We show here that the potency of inhibitory monoclonal
      antibody 33B8 measured with the new assay is consistent with its in vivo efficacy
      in PAI-1 inactivation. We also found that among the three monoclonal antibodies
      tested, the traditional solid phase assay caused mechanism dependent significant
      right shift of IC50 values. As our new assay avoids the use of non-physiological
      large quantities of uPA, we conclude that it is a better measure of
      pharmacodynamic effects of anti-PAI-1 antibodies in vivo.

PMID- 30278156
TI  - Regulation of cardiac calcium by mechanotransduction: Role of mitochondria.
AB  - Myocardium is subjected to a variety of forces with each contraction, such as
      stretch, afterload, and shear stress, and adapts to those mechanical stimuli.
      These mechanical stimuli increase in heart failure, valvular heart disease and
      hypertension that are clinically associated with arrhythmia and myocyte
      remodeling. To understand cellular and molecular basis of mechanical stress
      mediated cardiac dysfunction and remodeling, several experimental approaches have
      been successfully used in single cardiac myocytes. In this review, we will
      briefly summarize the current knowledge about the responses of cardiac myocytes
      to mechanical stimuli and underlying mechanisms in the context of Ca2+ signaling,
      with focusing on the role of mitochondria in these mechanotransductions. Recent
      evidence suggests that mechanotransduction, associated with mitochondrial
      metabolism, significantly alters Ca2+ signaling and ionic homeostasis in cardiac
      myocytes under shear stress or prolonged stretch, and that it may play a key role
      in the pathogenesis of heart failure.

PMID- 30278157
TI  - Detection of cholesterol bilayer domains in intact biological membranes:
      Methodology development and its application to studies of eye lens fiber cell
      plasma membranes.
AB  - Four purported lipid domains are expected in plasma membranes of the eye lens
      fiber cells. Three of these domains, namely, bulk, boundary, and trapped lipids,
      have been detected. The cholesterol bilayer domain (CBD), which has been detected
      in lens lipid membranes prepared from the total lipids extracted from fiber cell
      plasma membranes, has not yet been detected in intact fiber cell plasma
      membranes. Here, a saturation-recovery electron paramagnetic resonance spin
      labeling method has been developed that allows identification of CBDs in intact
      fiber cell plasma membranes of eye lenses. This method is based on saturation
      recovery signal measurements of the cholesterol-analog spin label located in the
      lipid bilayer portion of intact fiber cell membranes as a function of the partial
      pressure of molecular oxygen with which the samples are equilibrated. The
      capabilities and limitations of this method are illustrated for intact cortical
      and nuclear fiber cell plasma membranes from porcine eye lenses where CBDs were
      detected in porcine nuclear intact membranes for which CBDs were also detected in
      lens lipid membranes. CBDs were not detected in porcine cortical intact and lens
      lipid membranes. CBDs were detected in intact membranes isolated from both
      cortical and nuclear fiber cells of lenses obtained from human donors. The
      cholesterol content in fiber cell membranes of these donors was always high
      enough to induce the formation of CBDs in cortical as well as nuclear lens lipid
      membranes. The results obtained for intact membranes, when combined with those
      obtained for lens lipid membranes, advance our understanding of the role of high
      cholesterol content and CBDs in lens biology, aging, and/or cataract formation.

PMID- 30278158
TI  - Leveraging Community Engagement to Develop a Mobile Health Application for Older
      Women With HIV Infection.
AB  - OBJECTIVE: To develop a mobile health app for older women with HIV infection that
      will be used in a larger study. DESIGN: A qualitative study design. SETTING:
      Baltimore-Washington metropolitan area clinics and communities. PARTICIPANTS: Ten
      women 50 years and older (mean age = 62.8 years, standard deviation = 3.62, range
      = 58-69 years) who self-identified as Black or African American and were infected
      with HIV. METHODS: At the start of the study, we used relevant empirical and the
      self-determination theory to inform the draft Web-based app content that was
      shared with two focus groups. Data were analyzed with input from a community
      advisory board (CAB) to inform the development of the mobile health app. RESULTS:
      We inductively identified eight subthemes within the coding structure of two
      overall themes: Navigating Content, Functions, and Features and Enhancing
      Provider Interaction With Patients that represented the perspectives of
      participants regarding the app. From the eight subthemes, we integrated the
      contributions from the CAB, which we then used to further optimize the app.
      CONCLUSION: The app was designed to provide support, tools, and resources for
      older women with HIV. Engagement of community collaborators could be challenging
      because of multiple personal and structural barriers. Nonetheless, the potential
      community member benefits are invaluable. If successful, the Web-based app could
      be a model to address the needs of older persons with HIV infection.

PMID- 30278159
TI  - Auckland Cataract Study III: refining preoperative assessment with cataract risk
      stratification to reduce intraoperative complications.
AB  - PURPOSE: To assess intraoperative complications of phacoemulsification surgery in
      public teaching hospital settings using modified preoperative risk stratification
      systems. DESIGN: Prospective cohort study. METHODS: Preoperative risk
      stratification of 500 consecutive cataract cases using the New Zealand Cataract
      Risk Stratification (NZCRS) scoring system. Recommended allocation of higher-risk
      phacoemulsification procedures to experienced surgeons in public teaching
      hospital setting. Main outcome measure; intraoperative complications relative to
      adherence to stratification recommendations. RESULTS: NZCRS classified 192 cases
      (38%) as high-risk, recommended for Fellows or Consultants (Attendings). Primary
      surgeons: Residents (n=142, 28%), Fellows (n=88, 18%), Consultants (n=270, 54%).
      Overall rate (N=500) of any intraoperative complication was 5.0%. Where NZCRS
      scoring recommendations were observed (n=448) the intraoperative complication
      rate was 4.5% but in 'non-adherence' cases (n=52, Residents operating on higher
      risk cases) this nearly doubled (9.6%). Postoperative complications occurred in
      5.2%, primarily cystoid macular oedema (3.7%). Postoperatively, mean unaided
      visual acuity was 6/12 (20/40) and best-corrected visual acuity improved from
      6/20 (20/63) preoperatively to 6/10 (20/32) postoperatively (p<0.05).
      CONCLUSIONS: The NZCRS system aids identification of higher-risk cataract cases,
      appropriate case-to-surgeon allocation, and may increase surgeon awareness of
      risk factors. Compared to two previous studies under similar conditions in the
      same institution, the NZCRS system was associated with a 40% reduction in
      intraoperative complications (8.4% to 5%). The rate of posterior capsular tear
      was 0.6% (p= .035) compared to 2.6% in baseline phase and 1.4% in a prior risk
      stratification phase. Risk-stratification appears to reduce intraoperative
      phacoemulsification complications in public teaching hospital settings.

PMID- 30278160
TI  - Clinical and ophthalmic factors associated with the severity of sickle cell
      retinopathy.
AB  - PURPOSE: To identify associations between severity of sickle cell retinopathy
      (SCR) and other clinical, laboratory, or treatment factors relevant to sickle
      cell disease (SCD). DESIGN: Retrospective cohort study. METHODS: We investigated
      clinical, laboratory, and demographic associations with the severity of SCR in
      296 patients seen at both our SCD specialty clinic and our retina clinic.
      Multivariate multinomial logistic regression was used to estimate the association
      between each clinical variable and severity of SCR. RESULTS: Multivariate
      analysis showed that in patients with sickle cell anemia (SCA) genotypes, older
      age (95% confidence interval [CI], 1.04-1.15; P<0.001) and male gender (95% CI,
      0.13-0.87; P=0.02), were associated with proliferative sickle cell retinopathy
      (PSR). In patients with genotypic variants, visual symptoms (95% CI, 1.36-21.62;
      P=0.02) were associated with PSR. Laser photocoagulation and vitrectomy surgery,
      the standard interventions for PSR, were associated with older age (95% CI, 1.05
      1.13; P<0.001), visual symptoms (95% CI, 1.48-7.40; P=0.004), higher hemoglobin
      level (95% CI, 1.14-1.65; P=0.001), and no chronic transfusion (95% CI, 0.16
      1.09; P=0.08) across the whole cohort. CONCLUSIONS: These findings may inform
      clinicians of the symptoms, systemic findings, and disease modifying therapies
      most frequently associated with SCR in SCD patients. Visual symptoms such as
      blurred vision or floaters were associated with progression of SCR, and may be
      criteria for referral for retinal examination. Chronic transfusion therapy may be
      protective against the need for retinal laser photocoagulation or vitrectomy.
      Prospective studies are necessary to further explore risk factors for SCR and to
      identify which individuals with SCD are at risk for incident or progression of
      retinopathy.

PMID- 30278161
TI  - New insights into molecular mechanisms of rosiglitazone in monotherapy or
      combination therapy against cancers.
AB  - Rosiglitazone (ROSI), a member of thiazolidinediones (TZDs) which act as high
      affinity agonists of the nuclear receptor peroxisome-proliferator-activated
      receptor-gamma (PPARgamma), is clinically used as an antidiabetic drug which
      could attenuate the insulin resistance associated with obesity, hypertension, and
      impaired glucose tolerance in humans. However, recent studies reported that ROSI
      had significant anticancer effects on various human malignant tumor cells.
      Mounting evidence indicated that ROSI could exert anticancer effects through
      PPARgamma-dependent or PPARgamma-independent ways. In this review, we summarized
      the PPARgamma-dependent antitumor activities of ROSI, which included apoptosis
      induction, inhibition of cell proliferation and cancer metastasis, reversion of
      multidrug resistance, reduction of immune suppression, autophagy induction, and
      antiangiogenesis; and the PPARgamma-independent antitumor activities of ROSI,
      which included inhibition of nuclear factor kappa-light-chain-enhancer of
      activated B cells (NF-kappaB) pathway, inhibition of prostaglandin E2 (PGE2),
      increasing MAPK phosphatase 1 (MKP-1) expression and regulation of other
      apoptosis-related cell factors. In addition, we discussed the anti-cancer
      application of ROSI by monotherapy or combination therapy with present
      chemotherapeutic drugs in vitro and in vivo. Moreover, we reviewed the phase I
      cancer clinical trials related to ROSI combined with chemotherapeutics and phase
      II trials about the anti-cancer effects of ROSI monotherapy and the radiotherapy
      sensitivity of ROSI.

PMID- 30278162
TI  - Mechanistic studies on the effect of membrane lipid acyl chain composition on
      daptomycin pore formation.
AB  - Daptomycin is a lipopeptide antibiotic that binds and permeabilizes the cell
      membranes of Gram-positive bacteria. Membrane permeabilization requires both
      calcium and phosphatidylglycerol (PG) in the target membrane, and it correlates
      with the formation of an oligomer that likely comprises eight subunits, which are
      evenly distributed between the two membrane leaflets. In both bacterial cells and
      model membranes, changes in the fatty acyl composition of the membrane
      phospholipids can prevent permeabilization. We here used liposomes to study the
      effect of phospholipids containing oleoyl and other fatty acyl residues on
      daptomycin activity, and made the following observations: (1) Oleic acid residues
      inhibited permeabilization when part not only of PG, but also of other
      phospholipids (PC or cardiolipin). (2) When included in an otherwise daptomycin
      susceptible lipid mixture, even 10% of dioleoyl lipid (DOPC) can strongly inhibit
      permeabilization. (3) The inhibitory effect of fatty acyl residues appears to
      correlate more with their chain length than with unsaturation. (4) Under all
      conditions tested, permeabilization coincided with octamer formation, whereas
      tetramers were observed on membranes that were not permeabilized. Overall, our
      findings further support the notion that the octamer is indeed the functional
      transmembrane pore, and that fatty acyl residues may prevent pore formation by
      preventing the alignment of tetramers across the two membrane leaflets.

PMID- 30278163
TI  - 3-dimensional printed models-guided surgical repair for recurrent coronary artery
      fistula.
AB  - Recurrent coronary artery fistula is rare and can be difficult for surgical
      treatment because of anatomic complexity. Here, we reported one case of
      successful re-repair of a recurrent coronary artery fistula, which added evidence
      of the 3-dimensional printed models guiding surgical correction of complex
      intracardiac abnormalities.

PMID- 30278164
TI  - Video Assisted Thoracoscopic Lobectomy for Lung Cancer.
AB  - The use of video assisted thoracoscopic surgery (VATS) lobectomy has become a
      mainstay of modern day thoracic oncology practice and the technique of choice for
      resection of early stage lung cancers at many institutions. The feasibility of
      VATS lobectomy has long been well established and there is considerable belief
      that it leads to better patient outcomes. In the following review, we seek to
      summarize the current experience with VATS lobectomy, identify the strengths and
      weaknesses of the available literature and address future areas of research for
      our field.

PMID- 30278165
TI  - Neoadjuvant Therapy for Locally Advanced Esophageal Cancer Should Be Targeted to
      Tumor Histology.
AB  - BACKGROUND: Controversy exists over the optimal neoadjuvant therapy in patients
      with locally advanced esophageal cancer (EC). Although most groups favor
      neoadjuvant chemoradiation (nCRT), some prefer preoperative chemotherapy (nCT)
      without radiation. The objective of this study was to compare outcomes in EC
      patients undergoing either regimen, followed by surgery. METHODS: We reviewed a
      prospectively collected database of EC patients undergoing esophagectomy after
      nCT or nCRT from 1989 to 2016. Choice of therapy was at the discretion of the
      multidisciplinary team. Disease-free survival (DFS) and cancer-specific survival
      (CSS) were compared by the Kaplan-Meier log-rank test. Independent predictors of
      CSS were estimated by Cox regression analysis. RESULTS: Among 700 EC patients 338
      patients were treated with nCRT (n = 112) or nCT (n = 226) followed by surgery.
      Patients were well matched for age, gender, and clinical stage, although patients
      with squamous cell carcinoma were more likely to receive nCRT (49% vs 26%, p <
      0.001). At surgery 90% and 91% of nCRT and nCT patients, respectively, underwent
      transthoracic esophagectomy. nCRT, in comparison with nCT, was associated with
      similar rates of Calvien-Dindo grade III/IV complications (34% vs 33%, p = 0.423)
      but with a trend toward higher perioperative mortality (5% vs 1%, p = 0.064).
      Among adenocarcinoma patients (n = 239) the use of nCRT was associated with
      higher rates of complete clinical response (18% vs 7.4%), pathologically negative
      lymph nodes (52% vs 30%, p = 0.001), and complete pathologic response (21% vs
      5.1%, p < 0.001). However, there was no difference between nCRT and nCT for 5
      year DFS (28% vs 31%, p = 0.636) or CSS (51% vs 52%, p = 0.824) among
      adenocarcinoma patients. For patients with squamous cell carcinoma (n = 98), nCRT
      and nCT had similar rates of complete clinical response (31% vs 26%, p = 0.205),
      but the rates of negative nodes (65% vs 46%, p = 0.064) and of complete
      pathologic response (42% vs 12%, p < 0.05) were higher with nCRT. For these
      patients nCRT was associated with no statistical difference in 5-year DFS (57% vs
      40%, p = 0.595) but with improved 5-year CSS (87% vs 68%, p = 0.019) compared
      with nCT. On multivariable analysis for CSS, nCRT predicted improved survival for
      patients with squamous cell carcinoma (hazard ratio, 0.242; 95% confidence
      interval, 0.071-0.830) but not for those with adenocarcinoma (univariate hazard
      ratio, 0.940; 95% confidence interval, 0.544-1.623). CONCLUSIONS: For
      adenocarcinoma patients undergoing surgery for EC, nCRT leads to increased local
      tumor response compared with nCT alone but with no difference in survival. For
      squamous carcinoma patients nCRT appears to improve CSS compared with nCT. For
      patients with locally advanced EC targeted neoadjuvant regimens should be used
      depending on tumor histology.

PMID- 30278166
TI  - Tissue graft to cover diaphragmatic defects in a patient with catamenial
      pneumothorax.

PMID- 30278167
TI  - Standardized Haller and Asymmetry Index Combined for a More Accurate Assessment
      of Pectus Excavatum.
AB  - BACKGROUND: The measurement of the Haller index (HI) is not standardized, and HI
      does not consider the asymmetry of pectus excavatum. The aim of this study was to
      determine the most appropriate level for measuring the HI and to introduce the
      asymmetry index (AI) in order to respect the aspect of asymmetry. METHODS:
      Preoperative computer tomography scans of 43 patients with pectus excavatum were
      retrospectively analyzed by measuring both the HI and the AI at 3 different
      levels: (I) sternomanubrial junction; (II) caudal end of corpus sterni; and (III)
      tip of the xiphoid. The control group comprised 33 patients without chest wall
      deformity and a HI < 3.25. For each patient HI and AI were calculated according
      to a standardized protocol. A McNemar test was used for statistical analyses.
      RESULTS: The sensitivity of the HI was highest when measured at level II (p <
      0.388), and the AI exhibited the highest sensitivity at level I. When combining
      both indices, the sensitivity of assessing pectus excavatum significantly
      increased compared with the use of HI at level II alone (p < 0.002). CONCLUSIONS:
      The measurement of the HI at level II represents the most valid standardized
      parameter for assessment of the severity of pectus excavatum. Asymmetry, on the
      other hand, is best assessed by the AI measured at level I. The combination of
      the standardized HI and AI not only provides a much more accurate description of
      pectus excavatum, but also improves the comparability of pectus excavatum
      patients in general.

PMID- 30278168
TI  - Inhibition of MicroRNA-204 Conducts Neuroprotection Against Spinal Cord Ischemia.
AB  - BACKGROUND: MicroRNA(miR)-204 is an autophagy- and apoptosis-related gene.
      Neuroprotection by the inhibition of miR-204 against spinal cord ischemia was
      evaluated, and the roles of neuronal autophagy and apoptosis were investigated.
      METHODS: Spinal cord ischemia was conducted in rats by cross-clamping the
      descending aorta for 14 minutes. Inhibition of miR-204 was induced by intrathecal
      injection of lentivirus vectors containing antagomiR-204. Hind-limb motor
      function was assessed with the motor deficit index. Lumbar spinal cords were
      harvested for histologic examinations and terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick-end labeling staining. Autophagy was evaluated by the
      LC3-II/LC3-I ratio and beclin-1 expression. Expressions of LC3-I, LC3-II, beclin
      1, B-cell lymphoma-2 (BCL-2), caspase-3, and miR-204 were measured by Western
      blot and quantitative real-time polymerase chain reaction. Autophagy was blocked
      by 3-methyladenine. RESULTS: Transient ischemia enhanced miR-204 expression and
      the LC3-II/LC3-I ratio and downregulated BCL-2 expression in spinal cords in a
      time-dependent manner. AntagomiR-204 significantly reduced expressions of miR-204
      and caspase-3, dramatically upregulated expressions of beclin-1 and BCL-2 and the
      LC3-II/LC3-I ratio in spinal cords after reperfusion. Compared with controls,
      inhibition of miR-204 markedly decreased the motor deficit index scores at 6, 12,
      24, and 48 hours after reperfusion; increased the number of viable motor neurons;
      and decreased the number of apoptotic neurons. 3-Methyladenine completely
      abolished enhancements of the LC3-II/LC3-I ratio and beclin-1 expression induced
      by antagomiR-204 and inhibited the protective effect on hind-limb motor function.
      CONCLUSIONS: Inhibition of miR-204 exerts spinal cord protection against ischemia
      reperfusion injury, possibly via promotion of autophagy and antiapoptotic
      effects.

PMID- 30278169
TI  - Anomalous origin of left pulmonary artery from the aorta: a rare entity in
      congenital heart disease.
AB  - Anomalous origin of the left pulmonary artery (ALPA) from the aorta is a rare
      form of congenital heart disease, leading to long-term morbidity if not treated
      early. There is a reported association of this anomaly with 22q11 microdeletion
      syndrome. Surgical repair is commonly via direct reimplantation to the main
      pulmonary artery with or without patch or flap techniques. We present two unique
      cases of ALPA describing embryologic considerations for morphogenesis of ALPA
      with 22q11 microdeletion syndrome and a novel surgical technique involving
      unroofing of the unique anatomy of the common wall between the LPA and main
      pulmonary artery.

PMID- 30278170
TI  - Left Atrial Decompression Via Minithoracotomy During Extracorporeal Life Support.
AB  - Extracorporeal membrane oxygenation via cervical cannulation is an established
      option for pediatric patients with acute cardiopulmonary failure. However, left
      heart decompression is sometimes mandatory in patients with severe left
      ventricular dysfunction. We describe a fast and less invasive technique for
      placing a left atrial cannula through a left anterior minithoracotomy approach.
      In 4 critically ill children, this minimally invasive technique provided
      satisfactory left heart decompression, and we describe a representative case.

PMID- 30278171
TI  - Is There a Role for Cancer-Directed Surgery in Early-Stage Sarcomatoid or
      Biphasic Mesothelioma?
AB  - BACKGROUND: Benefits of surgical resection for early-stage nonepithelioid
      malignant pleural mesothelioma (MPM) have not been clearly elucidated. This study
      investigated whether cancer-directed surgery affects overall survival compared
      with nonsurgical therapies for T1-T2 N0 M0 sarcomatoid or biphasic MPM patients.
      METHODS: Adult patients with clinical stage I or II MPM were identified in the
      National Cancer Database from 2004 to 2103. Patients who underwent cancer
      directed surgery were matched by propensity score with patients who had received
      chemotherapy/radiotherapy or no treatments. Overall survival was compared using a
      Cox proportional hazard regression model. RESULTS: From National Cancer Database
      queries, 878 patients with clinical stage I or II MPM with sarcomatoid (n = 524)
      or biphasic (n = 354) histology were identified. Overall median survival was 5.5
      months for patients with sarcomatoid mesothelioma. The cancer-directed surgery
      improved overall survival compared with no operation (median survival, 7.56
      months vs 4.21 months, respectively; p < 0.01). In the biphasic group, median
      overall survival was 12.2 months. Again, the cancer-directed surgery improved
      survival compared with no operation (15.8 months vs 9.3 months, p < 0.01). For
      both histologies, the cancer-directed surgery improved overall survival compared
      with those who underwent chemotherapy or radiotherapy, or both, without resection
      (p < 0.05). Perioperative mortality was 6.0% at 30 days and 21.4% at 90 days.
      CONCLUSIONS: The cancer-directed surgery is associated with improved survival in
      early-stage MPM patients with nonepithelioid histology compared with those who
      did not undergo resection or chose medical therapy. Given the high perioperative
      mortality, a careful patient selection and multidisciplinary evaluation is
      recommended.

PMID- 30278172
TI  - Gross and histologic relationships of the retropubic urethra to lateral pelvic
      sidewall and anterior vaginal wall in female cadavers: clinical applications to
      retropubic surgery.
AB  - BACKGROUND: Knowledge of the retropubic space anatomy is essential for safe entry
      and surgical applications within this space. OBJECTIVE: The objectives of this
      study were to examine the gross and histologic anatomy of the retropubic urethra,
      paraurethral tissue, and urethrovaginal space and to correlate findings to
      retropubic procedures. STUDY DESIGN: Anatomic relationships of the retropubic
      urethra were examined grossly in unembalmed female cadavers. Measured distances
      included: lateral urethral wall to arcus tendineus fascia pelvis at the level of
      urethrovesical junction and at 1 cm distal. Other measurements included
      retropubic urethral length and distances from internal urethral opening to each
      ureteric orifice. Microscopic examination was performed at the same levels
      examined grossly in separate nulliparous specimens. Descriptive statistics were
      used for data analyses. RESULTS: In all, 25 cadavers were examined grossly.
      Median distance from lateral urethral wall to arcus tendineus fascia pelvis at
      the level of urethrovesical junction was 25 mm (range, 13-38 mm). At 1 cm distal,
      the median distance from aforementioned structures was 14 mm (10-26 mm). Median
      length of the retropubic urethra was 23 mm (range 15-30 mm). Four nulliparous
      specimens, ages 12 weeks, and 34, 47, and 52 years, were examined histologically.
      No histologic evidence of a discrete fascial layer between bladder/urethra and
      anterior vagina was noted at any level examined. Tissue between the urethra and
      the pelvic sidewall skeletal muscle was composed of dense fibrous tissue, smooth
      muscle bundles, scant adipose tissue, blood vessels, and nerves. The smooth
      muscle fibers of the vaginal muscularis interdigitated with skeletal muscle
      fibers in the pelvic sidewall at both levels examined. No histologic evidence of
      "pubourethral ligaments" within the paraurethral tissue was noticed. CONCLUSION:
      A 2-cm "zone of safety" exists between the urethra and arcus tendineus fascia
      pelvis at the urethrovesical junction level. Suture or graft placement within
      this region should minimize injury to the urethra, pelvic sidewall muscles, and
      bladder. Knowledge that the shortest length of retropubic urethra was 1.5 cm and
      shortest urethra to arcus tendineus fascia pelvis distance was 1 cm highlights
      the importance of maintaining dissection and trocar entry site close to pubic
      bone to avoid bladder and/or urethral injury. Histologic analysis of paraurethral
      tissue supports the nonexistence of pubourethral ligaments.

PMID- 30278173
TI  - The clinical heterogeneity of preeclampsia is related to both placental gene
      expression and placental histopathology.
AB  - BACKGROUND: Preeclampsia is a life-threatening disorder of pregnancy,
      demonstrating a high degree of heterogeneity in clinical features such as
      presentation, disease severity, and outcomes. This heterogeneity suggests
      distinct pathophysiological mechanisms may be driving the placental disease
      underlying this disorder. Our group recently reported distinct clusters of
      placental gene expression in preeclampsia and control pregnancies, allowing for
      the identification of at least 3 clinically relevant gene expression-based
      subtypes of preeclampsia. Histopathological examination of a small number of
      samples from 2 of the gene expression-based subtypes revealed placental lesions
      consistent with their gene expression phenotype, suggesting that detailed
      placental histopathology may provide further insight into the pathophysiology
      underlying these distinct gene expression-based subtypes. OBJECTIVES: The
      objective of the study was to assess histopathological lesions in the placentas
      of patients belonging to each identified gene expression-based subtype of
      preeclampsia, characterized in our previous study. Our goal was to further
      understand the pathophysiologies defining these gene expression-based subtypes by
      integrating gene expression with histopathological findings, possibly identifying
      additional subgroups of preeclampsia patients. STUDY DESIGN: Paraffin-embedded
      placental biopsies from patients included in the gene expression profiling study
      (n = 142 of 157, 90.4%) were sectioned, hematoxylin and eosin stained, and
      imaged. An experienced perinatal pathologist, blinded to gene expression findings
      and clinical information, assessed the presence and severity of histological
      lesions using a comprehensive, standardized data collection form. The frequency
      and severity scores of observed histopathological lesions were compared among
      gene expression-based subtypes as well as within each subtype using using Fisher
      exact tests, Kruskal-Wallis tests, and hierarchical clustering. The histological
      findings of the placental samples were visualized using t-distributed stochastic
      neighbor embedding and phylogenetic trees. Concordance and discordance between
      gene expression findings and histopathology were also investigated and visualized
      using principal component analysis. RESULTS: Several histological lesions were
      found to be characteristic of each gene expression-based preeclampsia subtype.
      The overall concordance between gene expression and histopathology for all
      samples was 65% (93 of 142), with characteristic placental lesions for each gene
      expression-based subtype complementing prior gene enrichment findings (ie,
      placentas with enrichment of hypoxia-associated genes showed severe lesions of
      maternal vascular malperfusion). Concordant samples were located in the central
      area of each gene expression-based cluster when viewed on a principal component
      analysis plot. Interestingly, discordant samples (gene expression and
      histopathology not reflective of one another) were generally found to lie at the
      periphery of the gene expression-based clusters and tended to border the group of
      patients with phenotypically similar histopathology. CONCLUSION: Our findings
      demonstrates a high degree of concordance between placental lesions and gene
      expression across subtypes of preeclampsia. Additionally, novel integrative
      analysis of scored placental histopathology severity and gene expression findings
      allowed for the identification of patients with intermediate phenotypes of
      preeclampsia not apparent through gene expression profiling alone. Future
      investigations should examine the temporal relationship between these 2
      modalities as well as consider the maternal and fetal contributions to these
      subtypes of disease.

PMID- 30278174
TI  - National mosaic embryo transfer practices: a survey.
AB  - BACKGROUND: The growing use of preimplantation genetic testing with in vitro
      fertilization has provided clinicians with more information about the genetics of
      embryos. Embryos, however, sometimes result with a mixed composition of both
      aneuploid and euploid cells, called mosaic embryos. The interpretation of these
      results has varied, leading some clinicians to transfer mosaic embryos and some
      opt not to. In addition, laboratories providing preimplantation genetic testing
      for aneuploidy have differing thresholds for determining an embryo aneuploid,
      mosaic, or euploid. Overall practice patterns for mosaic embryo transfer
      practices in the United States are unknown. OBJECTIVE(S): The objectives of the
      study were to characterize national mosaic embryo transfer practices, including
      the use of preimplantation genetic testing for aneuploidy, prior history of
      transferring mosaic embryos, thresholds for determining mosaicism, and
      willingness to transfer mosaic embryos among assisted reproductive technology
      clinics in the United States. STUDY DESIGN: A 14 question online survey assessing
      current use of preimplantation genetic testing for aneuploidy, thresholds for
      determining mosaicism, and clinic experience and willingness to transfer mosaic
      embryos was e-mailed to 405 assisted reproductive technology clinics across the
      United States. Descriptive statistics and logistic regression were used to
      analyze survey responses and identify clinical factors associated with reporting
      having ever transferred a mosaic embryo. RESULTS: Of the 405 US assisted
      reproductive technology clinics contacted, 252 (62.2%) completed a survey,
      including 157 private (62.3%), 55 academic (21.8%), and 40 hybrid (15.9%)
      clinics. Most clinics (168, 66.7%) reported conducting preimplantation genetic
      testing for aneuploidy on less than 50% of all in vitro fertilization cycles. The
      most common type of preimplantation genetic testing for aneuploidy technology
      used was next-generation sequencing at 88.9%. Ninety-one clinics (36.1%) receive
      mosaicism data on their preimplantation genetic testing for aneuploidy report;
      the most common thresholds for determining embryo aneuploidy and euploidy by
      clinics' primary genetics laboratories were <20% normal (36.3%) and >80% normal
      (46.2%), respectively. Thirty-nine (42.9%) of the 91 have transferred and 57
      (62.6%) would transfer a mosaic embryo. Nearly 40% of clinics were unsure about
      their thresholds for mosaic transfer and one fourth of clinics reported they had
      no threshold. Private (odds ratio, 1.0, 95% confidence interval, 0.5-1.8) and
      hybrid (odds ratio, 0.9, 95% confidence interval, 0.4-2.1) clinics were just as
      likely as academic clinics to report having transferred a mosaic embryo. Clinics
      in the northeastern United States were more likely to have transferred a mosaic
      embryo than clinics in other regions (odds ratio, 1.5, 95% confidence interval,
      0.9-2.7). Most clinics (72.6%) report they do not have a unique consent for
      transfer of mosaic embryos. CONCLUSION: There is uncertainty and variability in
      the transfer practices of mosaic embryos and classification of mosaicism among US
      assisted reproductive technology clinics. These findings provide an opportunity
      to establish mosaicism thresholds and create standardized guidelines for
      transferring mosaic embryos.

PMID- 30278175
TI  - Reply.

PMID- 30278176
TI  - Hospital variation in utilization and success of trial of labor after a prior
      cesarean.
AB  - BACKGROUND: Trial of labor after cesarean delivery is an effective and safe
      option for women without contraindications. OBJECTIVES: The objective of the
      study was to examine hospital variation in utilization and success of trial of
      labor after cesarean delivery and identify associated institutional
      characteristics and patient outcomes. STUDY DESIGN: Using linked maternal and
      newborn hospital discharge records and birth certificate data in 2010-2012 from
      the state of California, we identified 146,185 term singleton mothers with 1
      prior cesarean delivery and no congenital anomalies or clear contraindications
      for trial of labor at 249 hospitals. Risk-standardized utilization and success
      rates of trial of labor after cesarean delivery were estimated for each hospital
      after accounting for differences in patient case mix. Risk for severe maternal
      and newborn morbidities, as well as maternal and newborn length of stay, were
      compared between hospitals with high utilization and high success rates of trial
      of labor after cesarean delivery and other hospitals. Bivariate analysis was also
      conducted to examine the association of various institutional characteristics
      with hospitals' utilization and success rates of trial of labor after cesarean
      delivery. RESULTS: In the overall sample, 12.5% of women delivered vaginally.
      After adjusting for patient clinical risk factors, utilization and success rates
      of trial of labor after cesarean delivery varied considerably across hospitals,
      with a median of 35.2% (10th to 90th percentile range: 10.2-67.1%) and 40.5%
      (10th to 90th percentile range: 8.5-81.1%), respectively. Risk-standardized
      utilization and success rates of trial of labor after cesarean delivery
      demonstrated an inverted U-shaped relationship such that low or excessively high
      use of trial of labor after cesarean delivery was associated with lower success
      rate. Compared with other births, those delivered at hospitals with above-the
      median utilization and success rates of trial of labor after cesarean delivery
      had a higher risk for uterine rupture (adjusted risk ratio, 2.74, P < .001),
      severe newborn respiratory complications (adjusted risk ratio, 1.46, P < .001),
      and severe newborn neurological complications/trauma (adjusted risk ratio, 2.48,
      P < .001), but they had a lower risk for severe newborn infection (adjusted risk
      ratio, 0.80, P = .003) and overall severe unexpected newborn complications
      (adjusted risk ratio, 0.86, P < .001) as well as shorter length of stays
      (adjusted mean ratio, 0.948 for mothers and 0.924 for newborns, P < .001 for
      both). Teaching status, system affiliation, larger volume, higher neonatal care
      capacity, anesthesia availability, higher proportion of midwife-attended births,
      and lower proportion of Medicaid or uninsured patients were positively associated
      with both utilization and success of trial of labor after cesarean delivery.
      However, rural location and higher local malpractice insurance premium were
      negatively associated with the utilization of trial of labor after cesarean
      delivery, whereas for-profit ownership was associated with lower success rate.
      CONCLUSION: Utilization and success rates of trial of labor after cesarean
      delivery varied considerably across hospitals. Strategies to promote vaginal
      birth should be tailored to hospital needs and characteristics (eg, increase
      availability of trial of labor after cesarean delivery at hospitals with low
      utilization rates while being more selective at hospitals with high utilization
      rates, and targeted support for lower capacity hospitals).

PMID- 30278177
TI  - Reply.

PMID- 30278178
TI  - Experience with intrauterine device insertion in never sexually active
      adolescents: a retrospective cohort study.
AB  - BACKGROUND: Intrauterine devices can offer both contraceptive and
      noncontraceptive benefits to never sexually active adolescents. There are
      increasing data on intrauterine device use in adolescents; however, most data on
      intrauterine devices in adolescents are related to contraceptive use. There is
      very limited literature on intrauterine device placement in adolescents who have
      never been sexually active. OBJECTIVE: The objective of the study was to compare
      intrauterine device insertion success between never sexually active and sexually
      active cohorts. STUDY DESIGN: We performed a retrospective chart review of
      patients aged 10-20 years with attempted intrauterine device insertion at a
      children's hospital between October 2015 and September 2017. RESULTS: A total of
      210 patients were included, of whom 82 were never sexually active. Never sexually
      active adolescents were younger at insertion (15.6 vs 16.7 years, P < .001), more
      likely to have at least 1 medical problem (75.6% vs 54.7%, P = .046), and to have
      special needs (23.2% vs 4.7%, P < .001). Never sexually active adolescents were
      less likely to have intrauterine device insertion performed in the office setting
      (52.4% vs 94.5%, P < .001). There was no significant difference in success of
      intrauterine device insertion on the first attempt (90.2% vs 96.1%, P = .086). In
      a subanalysis of office insertions alone, never sexually active adolescents were
      more likely to have an unsuccessful intrauterine device insertion (16.3% vs 4.3%,
      P = .015) and less likely to tolerate the procedure well (81.4% vs 94.2%, P =
      .026). CONCLUSION: To our knowledge, this is the first study describing
      intrauterine device insertion in never sexually active patients. Although office
      success rates were lower, intrauterine device insertion in never sexually active
      adolescents was very successful overall, and intrauterine devices should be
      offered to this population.

PMID- 30278179
TI  - Addressing maternal mortality: the pregnant cardiac patient.
AB  - Cardiac disease in pregnancy is the number one indirect cause of maternal
      mortality in the United States. We propose a triad solution that includes
      universal screening for cardiovascular disease in pregnancy and postpartum women,
      patient education, and institution of a multidisciplinary cardiac team.
      Additionally, we emphasize essential elements to maximize care for the pregnant
      cardiac patient based on our experience at our institution in Bronx, NY.

PMID- 30278181
TI  - Association between serotonin-norepinephrine reuptake inhibitors and acute angle
      closure: what is known?
AB  - Serotonin-norepinephrine reuptake inhibitors (SNRIs) are widely used
      antidepressants with a relatively safe profile. One of the complications
      associated with this group of drugs is acute angle closure (AAC). The mechanisms
      linking SNRIs and AAC are complex and may be interlinked with the effects of the
      drug on the inhibition of serotonin and noradrenaline reuptake, as well as pseudo
      anticholinergic effects, dopaminergic effects, and idiosyncratic reactions with
      the drug molecule in the eye. Individual characteristics, such as polymorphisms
      of the gene encoding the 2D6 subunit of cytochrome P450, may affect the
      metabolism of the SNRI; while, the combination with other drugs may lead to an
      increased risk of iridocorneal angle closure, and may further exacerbate other
      mechanisms. Improved knowledge of the mechanisms linking SNRIs and AAC and of the
      risk factors predisposing to patients to AAC will reduce the number of patients
      affected by this dangerous complication.

PMID- 30278182
TI  - A 37 kDa Txp40 protein characterized from Photorhabdus luminescens sub sp.
      akhurstii conferred injectable and oral toxicity to greater wax moth, Galleria
      mellonella.
AB  - Photorhabdus luminescens is a gram-negative bacterium that symbiotically
      associates with insect-parasitic nematode, Heterorhabditis indica. Herein, we
      have characterized an insecticidal gene, Txp40 (1008 bp) from the indigenous
      isolates of P. luminescens, and tested its bioefficacy against Galleria
      mellonella via injectable and oral bioassay. The recombinant protein
      characterized from P. luminescens strain H3 exhibited comparatively greater
      insect toxicity than strain H1 in terms of LD50 and LT50 values. Txp40 holds
      great potential to replace Bt toxins in global agriculture.

PMID- 30278183
TI  - Expression of oestrogen receptor beta was negatively correlated with disease
      activity in patients with Crohn's disease involving the terminal ileum.
AB  - Crohn's disease (CD) is a chronic inflammatory disease. The recurrence and
      remission of symptoms in CD patients are associated with changes in hormones,
      such as in puberty, pregnancy, postpartum and menopause, reflecting that
      oestrogen and its receptor might play an important role in CD. The study aimed to
      investigate the expression and clinical significance of oestrogen receptor in
      patients with CD involving the terminal ileum. Expression of oestrogen receptor
      alpha (ERalpha) and oestrogen receptor beta (ERbeta) of 37 patients with CD
      involving the terminal ileum and 21 healthy controls was determined by
      immunohistochemistry. Disease activity was assessed by Harvey-Bradshow Crohn's
      disease activity index(Harvey-Bradshow CDAI). Expression of ERalpha was negative
      for all cases. Moreover, a reduction of ERbeta expression in patients with CD
      involving the terminal ileum was found, and ERbeta expression had a negative
      correlation with the disease activity index. These data indicate that ERbeta
      might be a predictor of CD activity and a new target for further study in CD
      endocrine therapy.

PMID- 30278180
TI  - Distribution of mechanical stress in the Escherichia coli cell envelope.
AB  - The cell envelope in Gram-negative bacteria comprises two distinct membranes with
      a cell wall between them. There has been a growing interest in understanding the
      mechanical adaptation of this cell envelope to the osmotic pressure (or turgor
      pressure), which is generated by the difference in the concentration of solutes
      between the cytoplasm and the external environment. However, it remains
      unexplored how the cell wall, the inner membrane (IM), and the outer membrane
      (OM) effectively protect the cell from this pressure by bearing the resulting
      surface tension, thus preventing the formation of inner membrane bulges, abnormal
      cell morphology, spheroplasts and cell lysis. In this study, we have used
      molecular dynamics (MD) simulations combined with experiments to resolve how and
      to what extent models of the IM, OM, and cell wall respond to changes in surface
      tension. We calculated the area compressibility modulus of all three components
      in simulations from tension-area isotherms. Experiments on monolayers mimicking
      individual leaflets of the IM and OM were also used to characterize their
      compressibility. While the membranes become softer as they expand, the cell wall
      exhibits significant strain stiffening at moderate to high tensions. We integrate
      these results into a model of the cell envelope in which the OM and cell wall
      share the tension at low turgor pressure (0.3 atm) but the tension in the cell
      wall dominates at high values (>1 atm).

PMID- 30278184
TI  - Human neuroblastoma SH-SY5Y cells treated with okadaic acid express
      phosphorylated high molecular weight tau-immunoreactive protein species.
AB  - BACKGROUND: Early stages of Alzheimer's disease (AD) are characterized by high
      phosphorylation of microtubule-associated protein tau, which may result from the
      downregulation of protein phosphatases. NEW METHOD: In order to model phosphatase
      downregulation and analyze its effect on tau aggregation in vitro, we treated
      neuroblastoma SH-SY5Y cells with okadaic acid (OA), a protein phosphatase
      inhibitor, and examined high molecular weight phospho-tau species. RESULTS AND
      COMPARISON WITH EXISTING METHODS: OA treatment led to the appearance of heat
      stable protein species with apparent molecular weight around 100 kDa, which were
      immunoreactive to anti-tau antibodies against phosphorylated Ser202 and Ser396.
      As these high molecular weight tau-immunoreactive proteins (HMW-TIPs)
      corresponded to the predicted size of two tau monomers, we considered the
      possibility that they represent phosphorylation-induced tau oligomers. We
      attempted to dissociate HMW-TIPs by urea and guanidine, as well as by alkaline
      phosphatase treatment, but HMW-TIPs were stable under all conditions tested.
      These characteristics resemble properties of certain sodium dodecyl sulfate (SDS)
      resistant tau oligomers from AD brains. The absence of HMW-TIPs detection by anti
      total tau antibodies Tau46, CP27 and Tau13 may be a consequence of epitope
      masking and protein truncation. Alternatively, HMW-TIPs may represent previously
      unreported phosphoproteins cross-reacting with tau. CONCLUSIONS: Taken together,
      our data provide a novel characterization of an OA-based cell culture model in
      which OA induces the appearance of HMW-TIPs. These findings have implications for
      further studies of tau under the conditions of protein phosphatase
      downregulation, aiming to explain mechanisms involved in early events leading to
      AD.

PMID- 30278185
TI  - Minimalistic in vitro systems for investigating tau pathology.
AB  - Neurofibrillary tangles, formed of hyperphosphorylated, misfolded tau
      accumulations, are a pathological hallmark of neurodegenerative diseases such as
      Alzheimer's disease (AD) and frontotemporal dementia. The neuroanatomical
      localisation of tau pathology in AD brains of different disease stages suggests
      that tau tangle pathology is spreading throughout the brain along connected
      neuronal circuits. Pathogenic tau can act as a prion-like seed, inducing the
      misfolding of native tau and leading to disease propagation throughout the brain.
      However, it is not yet fully understood how tau spreads between individual
      neurons or brain regions. Here, we review the models for investigating tau
      propagation in vitro, and summarise the findings from key studies into the
      mechanisms of tau pathology propagation in disease.

PMID- 30278186
TI  - Transgenerational plasticity and antiviral immunity in the Pacific oyster
      (Crassostrea gigas) against Ostreid herpesvirus 1 (OsHV-1).
AB  - The oyster's immune system is capable of adapting upon exposure to a pathogen
      associated molecular pattern (PAMP) to have an enhanced secondary response
      against the same type of pathogen. This has been demonstrated using poly(I:C) to
      elicit an antiviral response in the Pacific oyster (Crassostrea gigas) against
      Ostreid herpesvirus (OsHV-1). Improved survival following exposure to poly(I:C)
      has been found in later life stages (within-generational immune priming) and in
      the next generation (transgenerational immune priming). The mechanism that the
      oyster uses to transfer immunity to the next generation is unknown. Here we show
      that oyster larvae have higher survival to OsHV-1 when their mothers, but not
      their fathers, are exposed to poly(I:C) prior to spawning. RNA-seq provided no
      evidence to suggest that parental exposure to poly(I:C) reconfigures antiviral
      gene expression in unchallenged larvae. We conclude that the improved survival of
      larvae might occur via maternal provisioning of antiviral compounds in the eggs.

PMID- 30278187
TI  - Mechanistic Analysis of Cocrystal Dissolution, Surface pH, and Dissolution
      Advantage as a Guide for Rational Selection.
AB  - The dissolution behavior of a dibasic drug ketoconazole under the influence of pH
      has been evaluated and compared to its three 1:1 cocrystals with diacidic
      coformers, fumaric acid, succinic acid (SUC), and adipic acid. Mass transport
      models were developed by applying Fick's law of diffusion to dissolution with
      simultaneous chemical reactions in the hydrodynamic boundary layer adjacent to
      the dissolving surface to predict the interfacial pH and flux of the parent drug
      and cocrystals. All 3 cocrystals have the ability to modulate the interfacial pH
      to different extents compared to the parent drug due to the acidity of the
      coformers. Dissolution pH dependence of ketoconazole is significantly reduced by
      the cocrystallization with acidic coformers. Due to the different dissolution pH
      dependence, there exists a transition pH where the flux of the cocrystal is the
      same as the parent drug. Below this transition pH, the drug flux is higher, but
      above it, the cocrystal flux is higher. The development of these mass transport
      models provide a mechanistic understanding of the dissolution behavior and help
      identify cocrystalline solids with optimal dissolution characteristics.

PMID- 30278188
TI  - Nicotinamide Mononucleotide Adenylyltransferase 2 maintains neuronal structural
      integrity through the maintenance of golgi structure.
AB  - Golgi fragmentation and loss of Nicotinamide Mononucleotide Adenylyltransferase 2
      (NMNAT2) are the early key features of many neurodegenerative disorders. We
      investigated the link between NMNAT2 loss, Golgi fragmentation and axon
      degeneration. Golgi fragmentation in the cultured dorsal root ganglion (DRG)
      neurons resulted in caspase dependent axon degeneration and neuronal cell death.
      NMNAT2 depletion in the DRG neurons caused Golgi fragmentation and caspase
      dependent axon degeneration. NMNAT2 depletion did not cause ATP loss in the
      axons. These results indicate that NMNAT2 is required for maintenance of Golgi
      structure. Loss of Golgi structure or Nmnat2 depletion causes caspase dependent
      neurodegeneration. cytNmnat1 overexpression inhibited the axon degeneration
      induced by Golgi fragmentation or NMNAT2 depletion. These results also suggest
      that these degeneration signals converge on a common cytNmnat1 mediated axon
      protective program and are distinct from the SARM1 mediated caspase independent
      axon degeneration.

PMID- 30278189
TI  - Enhancement of fear learning in PPARalpha knockout mice.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the
      nuclear receptor superfamily and regulates fatty acid oxidation. Although
      PPARalpha is expressed not only in the peripheral tissues but also in the brain,
      its role in higher brain function is unclear. In this study, we investigated the
      role of PPARalpha in the control of behavior, including memory/learning and mood
      change, using PPARalpha knockout (KO) mice. A significant difference between wild
      type (WT) and KO mice was seen in the passive avoidance test, demonstrating that
      KO mice showed enhanced fear leaning. In the amygdala of KO mice, the levels of
      dopamine and its metabolites were increased, and the mRNA expression of dopamine
      degrading enzyme was decreased. When dopamine D1 receptor antagonist was
      administered, the enhanced fear learning observed in KO mice was attenuated.
      These results suggest that PPARalpha is involved in the regulation of emotional
      memory via the dopamine pathway in the amygdala.

PMID- 30278190
TI  - Twitter Mentions and Academic Citations in the Urologic Literature.
AB  - OBJECTIVE: To quantify the relationship between the number of Twitter mentions
      and the number of academic citations a urologic publication receives. MATERIALS
      AND METHODS: Two hundred and thirteen papers from 7 prominent urologic journals
      were examined 37 months after publication. Articles were evaluated with 2
      citation based "bibliometrics" (Scopus, Google Scholar) and Twitter mentions were
      tracked using the Altmetric Bookmarklet. The number of article citations and
      Twitter mentions were compared using one-way Analysis of variance (ANOVA) and
      bivariate fit analysis. RESULTS: Seventy-three percent of articles had at least 1
      Twitter mention. Forty-two percent of Twitter mentions occurred within the first
      week of the online publication date. Articles mentioned on Twitter had 2.0-fold
      more Scopus citations (P <.01), and 2.3-fold more Google Scholar citations (P <.
      01) compared to articles with no Twitter mentions. Female urologic articles had
      the greatest number of Twitter mentions (5.7 mentions/article) while pediatric
      urology had the fewest mean number of Twitter mentions (0.8 mentions/article). A
      total of 8.9% of papers were tweeted by their authors. Author tweeted articles
      were associated with a 12.3 (2.0-fold) and 15.5 (1.8-fold) mean citation increase
      for Scopus and Google Scholar (P <. 01 and P = . 01) compared to articles not
      shared by their authors on Twitter. CONCLUSION: The majority of urologic
      publications are being shared on Twitter. The number of citations a urologic
      publication receives up to 3 years after release is positively associated with
      the number of mentions it has on Twitter. Twitter activity may be an early
      indicator of ultimate academic impact of an academic urologic paper.

PMID- 30278191
TI  - Dengue virus enters and exits epithelial cells through both apical and
      basolateral surfaces and perturbs the apical junctional complex.
AB  - Dengue is the most relevant mosquito-borne viral disease in the world. It has
      been estimated that 390 million infections of dengue occur each year. Dengue
      virus (DENV) infection can be asymptomatic or can produce a self-limited febrile
      illness called dengue fever (DF) or a severe form of the infection called severe
      dengue. In some viruses, the entry and egress from cells, occur in a specific
      domain of polarized endothelial and epithelial cells. In this study, we
      investigated whether the entry and release of DENV was polarized in epithelial
      cells, and evaluated the effect of DENV infection on cellular junctions of
      epithelial cells. We used MDCK epithelial cells, which serve as an excellent
      model to study a functional barrier due to the presence of an apical junctional
      complex (AJC), and showed that entry and release of DENV from the cells, is
      bipolar. Additionally, we performed paracellular flux, diffusion of membrane
      lipid, immunofluorescence and immunoblotting assays to evaluate the integrity of
      the AJC during DENV infection. We observed that at later stages of infection,
      DENV altered the barrier function causing a decrease in the transepithelial
      electrical resistance and the degradation and delocalization of TJ and AJ
      proteins. The present study contributes to understand how DENV traverse epithelia
      in order to cause a productive infection, and provides insights into the
      mechanism of DENV pathogenesis.

PMID- 30278192
TI  - G protein-coupled receptor heteromers are key players in substance use disorder.
AB  - G protein-coupled receptors (GPCR) represent the largest family of membrane
      proteins in the human genome. Physical association between two different GPCRs is
      linked to functional interactions which generates a novel entity, called
      heteromer, with specific ligand binding and signaling properties.
      Heteromerization is increasingly recognized to take place in the
      mesocorticolimbic pathway and to contribute to various aspects related to
      substance use disorder. This review focuses on heteromers identified in brain
      areas relevant to drug addiction. We report changes at the molecular and cellular
      levels that establish specific functional impact and highlight behavioral outcome
      in preclinical models. Finally, we briefly discuss selective targeting of native
      heteromers as an innovative therapeutic option.

PMID- 30278193
TI  - Systematic review of co-occurring OCD and TD: Evidence for a tic-related OCD
      subtype?
AB  - OBJECTIVE: The aim of this review is to summarize the current knowledge of
      associated features of co-occurring obsessive-compulsive disorder (OCD) and tic
      disorders (TD) and to critically evaluate hypotheses regarding the nature of
      their comorbidity. METHOD: We conducted a systematic review following PRISMA
      guidelines. To this aim, the PubMed, PsychInfo and ISI Web of Knowledge databases
      were searched up to August 30, 2018. For gender and age-of-onset we additionally
      conducted meta-analyses. RESULTS: One hundred eighty-nine studies met inclusion
      criteria. We substantiate some acknowledged features and report evidence for
      differential biological mechanisms and treatment response. In general, studies
      were of limited methodological quality. CONCLUSIONS: Several specific features
      are reliable associated with co-occurring OCD + TD. The field lacks
      methodological sound studies. The review found evidence against and in favor for
      different hypotheses regarding the nature of comorbidity of OCD and TD. This
      could indicate the existence of a stepwise model of co-morbidity, or could be an
      artefact of the low methodological quality of studies.

PMID- 30278194
TI  - Social touch during development: Long-term effects on brain and behavior.
AB  - In this paper, our goal is to explore what is known about the role of social
      touch during development. We first address the neural substrates of social touch
      and the role of tactile experience in neural development. We discuss natural
      variation in early exposure to social touch, followed by a discussion on
      experimental manipulations of social touch during development and "natural
      experiments", such as early institutionalization. We then consider the role of
      other developmental and experiential variables that predict social touch in
      adults. Throughout, we propose and consider new theoretical models of the role of
      social touch during development on later behavior and neurobiology.

PMID- 30278196
TI  - Longitudinal Study of Dark Adaptation as a Functional Outcome Measure for Age
      Related Macular Degeneration.
AB  - PURPOSE: To investigate the natural history of dark adaptation (DA) function as
      measured by the change in rod intercept time (RIT) over 4 years and to correlate
      RIT change with age-related macular degeneration (AMD) severity. DESIGN:
      Longitudinal, single-center, observational study. PARTICIPANTS: A total of 77
      participants aged >=50 years with a range of AMD severities. METHODS:
      Participants each contributing a single study eye to the analysis were assigned
      into person-based AMD severity groups based on fundus characteristics (drusen,
      pigmentary changes, late AMD, and subretinal drusenoid deposits [SDDs]). The DA
      function was assessed in study eyes at baseline and 3, 6, 12, 18, 24, 36, and 48
      months. Mean change in DA function over time was calculated using the slope of
      linear regression fits of longitudinal RIT data. Patient-reported responses on a
      Low Luminance Questionnaire (LLQ) were obtained at baseline and yearly.
      Nonparametric statistical testing was performed on all comparisons. MAIN OUTCOME
      MEASURE: The RIT, defined as the time taken after a photobleach for visual
      sensitivity to recover detection of a 5*10-3 cd/m2 stimulus (a decrease of 3 log
      units), was monitored in study eyes over 4 years, and the mean rate of change was
      computed. RESULTS: Longitudinal analysis of 65 study eyes followed on the
      standard testing protocol (mean age, 71+/-9.3 years; 49% were female) revealed
      that higher rates of RIT prolongation were correlated with AMD severity group
      assignment at baseline (P = 0.026) and with severity group assignments at year 4
      (P = 0.0011). Study eyes that developed SDD during follow-up demonstrated higher
      rates of RIT prolongation relative to those that did not (P < 0.0001). Overall,
      higher rates of RIT prolongation were significantly correlated with greater 4
      year decreases in LLQ scores (total mean score, P = 0.0032). CONCLUSIONS:
      Longitudinal decline in DA function, which correlated with patient-reported
      functional deficits, was accelerated in eyes with greater AMD severity and
      especially in eyes with SDD both at baseline and at 4 years. The RIT prolongation
      as a measure of changing DA function may be a functional outcome measure in AMD
      clinical studies.

PMID- 30278197
TI  - Selective Laser Trabeculoplasty versus Argon Laser Trabeculoplasty in Glaucoma
      Patients Treated Previously with 360 degrees  Selective Laser Trabeculoplasty: A
      Randomized, Single-Blind, Equivalence Clinical Trial.
AB  - PURPOSE: The effectiveness of selective laser trabeculoplasty (SLT) was compared
      with argon laser trabeculoplasty (ALT) in a randomized clinical trial for
      patients with medically uncontrolled open-angle glaucoma who have previously
      received 360 degrees  SLT. DESIGN: An active equivalence parallel armed
      randomized control trial. PARTICIPANTS: Patients with open-angle glaucoma
      including pigmentary dispersion syndrome and pseudoexfoliation syndrome were
      enrolled into the study from 7 different sites across Canada. METHODS: One
      setting of 180 degrees  of either SLT or ALT was assigned randomly and applied to
      each participant. MAIN OUTCOME MEASURES: The change in intraocular pressure (IOP)
      from baseline to 12 months was compared between the 2 groups. RESULTS: A total of
      132 patients were recruited, 2 of which dropped out early in the study, leaving
      130 patients who completed the study as per protocol. For those, the study's
      primary outcome was calculated. The IOP change at 1 year in comparison to
      baseline for SLT vs. ALT was found to be different by 0.33 mmHg between the 2
      groups (3.16 for SLT and 2.83 for ALT) and was not statistically significant (P =
      0.71) Further analysis, though, showed that SLT had a significantly lower IOP
      reduction at early time points: 1 week and 1 month, but this effect was lost by 3
      months. Corresponding to this finding was the strong trend for ALT to fail more
      quickly than SLT. Although repeatable, the first repeat SLT reduced IOP to only
      about half compared with initial SLT treatment. CONCLUSIONS: The comparison at 12
      months following the laser therapy showed that both modalities lowered the IOP
      with approximately 3 mmHg, yet essentially all of the time-to-failure analyses
      favored SLT over ALT. The repeat SLT effect was found to be half of the initial
      treatment.

PMID- 30278195
TI  - Meta-analyses of the neural mechanisms and predictors of response to
      psychotherapy in depression and anxiety.
AB  - Understanding the neural mechanisms underlying psychological therapy could aid
      understanding of recovery processes and help target treatments. The dual-process
      model hypothesises that psychological therapy is associated with increased
      emotional-regulation in prefrontal brain regions and decreased implicit emotional
      reactivity in limbic regions; however, research has yielded inconsistent
      findings. Meta-analyses of brain activity changes accompanying psychological
      therapy (22 studies, n = 352) and neural predictors of symptomatic improvement
      (11 studies, n = 293) in depression and anxiety were conducted using seed-based d
      mapping. Both resting-state and task-based studies were included, and analysed
      together and separately. The most robust findings were significant decreases in
      anterior cingulate/paracingulate gyrus, inferior frontal gyrus and insula
      activation after therapy. Cuneus activation was predictive of subsequent symptom
      change. The results are in agreement with neural models of improved emotional
      reactivity following therapy as evidenced by decreased activity within the
      anterior cingulate and insula. We propose compensatory as well as corrective
      neural mechanisms of action underlie therapeutic efficacy, and suggest the dual
      process model may be too simplistic to account fully for treatment mechanisms.
      More research on predictors of psychotherapeutic response is required to provide
      reliable predictors of response.

PMID- 30278198
TI  - Construction and application of (Q)SAR models to predict chemical-induced in
      vitro chromosome aberrations.
AB  - In drug development, genetic toxicology studies are conducted using in vitro and
      in vivo assays to identify potential mutagenic and clastogenic effects, as
      outlined in the International Council for Harmonisation (ICH) S2 regulatory
      guideline. (Quantitative) structure-activity relationship ((Q)SAR) models that
      predict assay outcomes can be used as an early screen to prioritize
      pharmaceutical candidates, or later during product development to evaluate safety
      when experimental data are unavailable or inconclusive. In the current study, two
      commercial QSAR platforms were used to build models for in vitro chromosomal
      aberrations in Chinese hamster lung (CHL) and Chinese hamster ovary (CHO) cells.
      Cross-validated CHL model predictive performance showed sensitivity of 80 and
      82%, and negative predictivity of 75 and 76% based on 875 training set compounds.
      For CHO, sensitivity of 61 and 67% and negative predictivity of 68 and 74% was
      achieved based on 817 training set compounds. The predictive performance of
      structural alerts in a commercial expert rule-based SAR software was also
      investigated and showed positive predictivity of 48-100% for selected alerts.
      Case studies examining incorrectly-predicted compounds, non-DNA-reactive
      clastogens, and recently-approved pharmaceuticals are presented, exploring how an
      investigational approach using similarity searching and expert knowledge can
      improve upon individual (Q)SAR predictions of the clastogenicity of drugs.

PMID- 30278199
TI  - Effect of melatonin on attenuating the isoflurane-induced oxidative damage is
      related to PKCalpha/Nrf2 signaling pathway in developing rats.
AB  - Isoflurane, an inhalational anesthesia, has frequently been used in pediatric
      anesthesia. However, research indicates that isoflurane can induce oxidative
      stress and affect neural and cognitive development. Melatonin, an endogenous
      hormone that exhibits antioxidant functions, can play a neuroprotective role by
      activating the PKCalpha/Nrf2 signaling pathway in response to oxidative stress.
      This study aims to determine whether the effect of melatonin on isoflurane
      induced oxidative stress is related to activation of the PKCalpha/Nrf2 signaling
      pathway. Rat pups at postnatal day 7 were treated with control or 1.5% isoflurane
      for 4 h after pretreatment for 15 min with either melatonin (10 mg/kg i.p.) or 1%
      ethanol. The hematoxylin and eosin staining and transmission electron microscopic
      examination were used for observation of histopathology. The oxidative stress
      related indicators were detected by using assay kits. The western blotting,
      immunohistochemistry and immunofluorescence were used to detect the activation of
      PKCalpha/Nrf2 signaling pathway. Results showed that isoflurane induced nerve
      damage in the hippocampus, and melatonin could reduce this injury. Oxidative
      stress-related indicators suggested that isoflurane can significantly increase
      reactive oxygen species and malondialdehyde levels, and decrease superoxide
      dismutase and glutathione activity compared with the control group, whereas
      melatonin ameliorated these indices. Expression of proteins associated with the
      PKCalpha/Nrf2 signaling pathway indicated that the neuroprotective effect of
      melatonin is related to activation of the PKCalpha/Nrf2 signaling pathway. These
      results suggest that the attenuating effect of melatonin on isoflurane-induced
      oxidative stress is related to activation of the PKCalpha/Nrf2 signaling pathway.
      These findings promote further research into underlying mechanisms and effective
      treatments to attenuate anesthesia neurotoxicity.

PMID- 30278200
TI  - Antidepressant-like effects of insulin and IGF-1 are mediated by IGF-1 receptors
      in the brain.
AB  - Depression is associated with uncontrolled diabetes, which indicates a lack of
      insulin effect, yet the role of the insulin receptor in mediating depression is
      not clearly established because insulin receptors are not required for glucose
      entry into the brain. However, insulin receptors are important for brain function
      since insulin receptor knockout mice have depressive-like activity. Depression
      and cognitive problems are also associated with low insulin-like growth factor-1
      (IGF-1) in the elderly. Rodent studies showed chronic IGF-1 administration had
      antidepressant-like (AD) activity. We asked if insulin in the brain might act
      through the IGF-1 receptor, as it does in some tissues. We used acute insulin or
      IGF-1 infusions into the 3rd ventricle (icv) in rats and tested animals in a
      forced swim test. We found that antidepressive-like behavior is mediated by
      insulin and IGF-1. Further, administration of the IGF-1 receptor antagonist JB-1
      blocked the antidepressive-like activity of the insulin and IGF-1, indicating a
      strong relationship between insulin, IGF-1 and depression. Insulin acts at least
      partially through the IGF-1 receptor and is responsive to receptor antagonism.
      The model offers promise for future studies of the mechanism of depression, and
      therapy to increase insulin sensitivity and IGF-1 action including exercise and
      nutrition.

PMID- 30278201
TI  - Cell differentiation processes as spatial networks: Identifying four-dimensional
      structure in embryogenesis.
AB  - One overarching principle of eukaroytic development is the generative spatial
      emergence and self-organization of cell populations. As cells divide and
      differentiate, they and their descendents form a spatiotemporal explicit and
      increasingly compartmentalized complex system. Yet despite this
      comparmentalization, there is selective functional overlap between these
      structural components. While contemporary tools such as lineage trees and
      molecular signaling networks prvide a window into this complexity, they do not
      characterize embryogenesis as a global process. Using a four-dimensional spatial
      representation, major features of the developmental process are revealed. To
      establish the role of developmental mechanisms that turn a spherical embryo into
      a highly asymmetrical adult phenotype, we can map the outcomes of the cell
      division process to a complex network model. This representational model provides
      information about the top-down mechanisms relevant to the differentiation
      process. In a complementary manner, looking for phenomena such as superdiffusive
      positioning and sublineage-based anatomical clustering incorporates dynamic
      information to our parallel view of embryogenesis. Characterizing the spatial
      organization and geometry of embryos in this way allows for novel indicators of
      developmental patterns both within and between organisms.

PMID- 30278202
TI  - Computational, theoretical, and experimental approaches to morphogenesis.

PMID- 30278203
TI  - Duration of therapeutic hypothermia or targeted temperature management in
      pediatric cardiac arrest: Seeing through the ice.

PMID- 30278204
TI  - Enhancement of capnogram waveform in the presence of chest compression artefact
      during cardiopulmonary resuscitation.
AB  - BACKGROUND: Current resuscitation guidelines emphasize the use of waveform
      capnography to help guide rescuers during cardiopulmonary resuscitation (CPR).
      However, chest compressions often cause oscillations in the capnogram, impeding
      its reliable interpretation, either visual or automated. The aim of the study was
      to design an algorithm to enhance waveform capnography by suppressing the chest
      compression artefact. METHODS: Monitor-defibrillator recordings from 202 patients
      in out-of-hospital cardiac arrest were analysed. Capnograms were classified
      according to the morphology of the artefact. Ventilations were annotated using
      the transthoracic impedance signal acquired through defibrillation pads. The
      suppression algorithm is designed to operate in real-time, locating distorted
      intervals and restoring the envelope of the capnogram. We evaluated the
      improvement in automated ventilation detection, estimation of ventilation rate,
      and detection of excessive ventilation rates (over-ventilation) using the
      capnograms before and after artefact suppression. RESULTS: A total of 44 267
      ventilations were annotated. After artefact suppression, sensitivity (Se) and
      positive predictive value (PPV) of the ventilation detector increased from
      91.9/89.5% to 98.0/97.3% in the distorted episodes (83/202). Improvement was most
      noticeable for high-amplitude artefact, for which Se/PPV raised from 77.6/73.5%
      to 97.1/96.1%. Estimation of ventilation rate and detection of over-ventilation
      also upgraded. The suppression algorithm had minimal impact in non-distorted
      data. CONCLUSION: Ventilation detection based on waveform capnography improved
      after chest compression artefact suppression. Moreover, the algorithm enhances
      the capnogram tracing, potentially improving its clinical interpretation during
      CPR. Prospective research in clinical settings is needed to understand the
      feasibility and utility of the method.

PMID- 30278205
TI  - Transcriptomics and metabonomics of the anti-aging properties of total flavones
      of Epimedium in relation to lipid metabolism.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Total flavones of Epimedium (TFE) is the main
      active ingredient in Herba Epimedii, which is a well-known Chinese herbal
      medicine that is widely used to treat certain age-related diseases in oriental
      countries. AIM OF THE STUDY: The aim of this work was to investigate the anti
      aging properties of TFE related to lipid metabolism. MATERIALS AND METHODS: Both
      transcriptomics and metabonomics were applied in this work to investigate the
      anti-aging properties of TFE. Microarray and LC-MS analysis were conducted on
      liver samples of three groups of rats, including young (4 months), old (24
      months), and old rats administrated TFE. RESULTS: Transcriptomics analysis
      highlighted 287 transcripts related to the anti-aging effect of TFE, in which the
      expression ratio of 18 genes regulating lipid metabolism, including HMGCS1 and
      NR1H3, returned to normal levels after TFE treatment. In addition, 24 aging
      related metabolites were discovered in a metabonomics study, and 15 of these were
      structurally identified, including palmitic amide, linoleamide, and oleamide.
      Bioinformatics and integral data analysis on the results of the transcriptomics
      and metabonomics suggest the involvement of 12 key metabolic pathways, half of
      which are highly related to lipid metabolism. CONCLUSIONS: This study
      demonstrates that the role played by TFE in the lipid metabolism of aging rats is
      multifaceted and multi-layered.

PMID- 30278206
TI  - Bacillus thuringiensis Cry1A toxins exert toxicity by multiple pathways in
      insects.
AB  - Adoption of biotech crops engineered to express insecticidal toxins from Bacillus
      thuringiensis (Bt) has revolutionized insect pest control in agriculture. For
      continuing effective application and development of the environmentally friendly
      Bt biotechnology, it is fundamental to understand pathways of toxicity of Bt
      toxins in insects. In this study, mutations were introduced in the midgut
      cadherin gene in the cabbage looper, Trichoplusia ni, by CRISPR/Cas9 mutagenesis.
      T. ni strains with mutations in the genes of two major receptors for Bt toxins,
      the midgut cadherin and ABCC2, and three Cry1A toxins with shared and
      differential midgut binding sites were used as an experimental system to dissect
      the roles of the cadherin and ABCC2 in the pathways of toxicity of Bt toxins.
      Results from assays of responses of the T. ni strains to different Bt toxins
      revealed that the cadherin and ABCC2 play independent roles in the mode of action
      of Cry1A toxins and that Bt toxins exert insecticidal activity through multiple
      redundant pathways of toxicity in insects. Besides the cadherin and ABCC2
      pathways, there exists an additional major pathway of toxicity to be identified
      for Cry1Aa. The results also confirmed that the toxicity of Cry2Ab involves
      neither the cadherin nor the ABCC2 protein. The multiple pathway model for Bt
      toxins clarified from this study provided new insights into the molecular modes
      of action of Bt toxins and mechanisms of insect resistance to Bt toxins.

PMID- 30278207
TI  - Proteomics reveals localization of cuticular proteins in Anopheles gambiae.
AB  - Anopheles gambiae devotes over 2% of its protein coding genes to its 298
      structural cuticular proteins (CPs). This paper provides new LC-MS/MS data on two
      adult structures, proboscises and palps, as well as three larval samples - 4th
      instar larvae, just their terminal segment, and a preparation enriched in their
      tracheae. These data were combined with our previously published results of
      proteins from five other adult structures, whole adults, and two preparations
      chosen for their relatively clean cuticle, the larval head capsules left behind
      after ecdysis and the pupal cuticles left behind after adult eclosion. Peptides
      from 28 CPs were recovered in all adult structures; 24 CPs were identified for
      the first time, 6 of these were members of the TWDL family. Most newly identified
      proteins came from the larval sources. Based solely on peptide recovery, from our
      data and from other investigators, most available on VectorBase, there were only
      4 CPs that were restricted to a single adult structure. More were restricted to a
      single metamorphic stage, 14 in larvae, 0 in pupae and 32 in adults. Expression
      data from our earlier RT-qPCR studies reduces these numbers. Charting restriction
      of CPs to stage or structure is a step forward in establishing their specific
      roles.

PMID- 30278208
TI  - Bacterial respiratory tract inflammation in neonatal rat model is attenuated by
      benzofuran through inhibition of GATA3.
AB  - The current study was aimed to investigate the effect of benzofuran on asthma
      neonatal rat model. Twenty-five neonatal rats were assigned into five groups;
      Normal control, untreated, 1 mg/kg, 8 mg/kg and 10 mg/kg treatment groups.
      Methacholine was administered orally to the rats of untreated and treatment
      groups. Animals in the normal control group were given PBS as a vehicle.
      FlexiVent system employing a computer-controlled mouse ventilator along with
      respiratory mechanics was used for the analysis of airway resistance in the rats.
      Cytokine level and IFN-gamma in the rat serum samples was performed by ELISA in
      accordance with the instructions of manufacturer. Methacholine administration
      into the rats caused a marked increase in lung airway resistance. However,
      treatment with 8 and 10 mg/kg doses of benzofuran led to marked decrease in the
      airway resistance. Benzofuran treatment prevented accumulation of macrophages and
      inflammatory cells in the lung airways. Inhibition of inflammation in
      methacholine administered rats by benzofuran was also confirmed by hematoxylin &
      eosin-staining. Examination of the rat serum showed significantly higher level of
      Th2 cytokines (IL-4, -5 and -13) in the untreated rats. However, treatment of
      methacholine administered rats with benzofuran significantly inhibited Th2
      cytokine expression. The level of IFN-gamma was increased by benzofuran treatment
      in methacholine administered rats. In methacholine administered rats the level of
      IgE was markedly higher however treatment of asthma rats with benzofuran
      inhibited up-regulation of IgE significantly. The expression of T-bet is
      decreased and that of GATA-3 is increased by methacholine administration in the
      rat lungs. Benzofuran treatment of methacholine administered rats prevented
      reduction in T-bet and up-regulation of GATA-3 expression in the rat lungs. The
      effect of benzofuran was significant at the doses of 8 and 10 mg/kg and non
      significant at 1 mg/kg. These finding suggest that benzofuran inhibits expression
      of dominant T-helper 2 cytokines through targeting GATA-binding protein 3
      transcription factor. Thus benzofuran can be of therapeutic importance for the
      treatment of asthma.

PMID- 30278209
TI  - Structural and functional characterization for interaction of silver
      nanoparticles with ergostrol in Trichoderma harzianum.
AB  - Silver ions, because of its recognised antimicrobial activity are reported in
      several regions for the very long time while ergosterol, apart from its role as a
      secondary metabolite, structural component of the fungal cell membranes, also
      turns out to be activating defence response in plants. Silver ions biosynthesized
      by terpene ergosterol producing Trichoderma harzianum could be used against other
      plant pathogenic fungi. In this work, possible interaction of the silver ions
      with ergosterol enzyme has been investigated using a computational approach.
      Protein model construction via prior knowledge of sequences and molecular ligand
      docking experiments as well as structural and sequence comparisons were executed
      to identify potential active-site in ergosterol enzyme. Moldock score of -48.5747
      with the reranking score of -40.0228 has been reported by Molegro Virtual
      Docker(MVD) at ergosterol enzyme's active site positions for silver ion. Apart
      from the core of the active site, four other positions have been occupied by
      silver ion. The interacting site surrounded by Cys339, Arg343, Lue365, Leu336 and
      Trp371 formed hydrophobic bonds with silver. The anti-microbial activity against
      phytopathogens is believed to increase synergistically when combined with
      ergosterol enzyme. Thus the computational analysis of silver ion in conjugation
      with ergosterol enzyme provided additional strategies to improve the ability of
      the Trichoderma strains in biocontrol of pathogenic fungi. In the present study,
      silver ion based formulations which are produced by strong bio-control fungi as
      shown were estimated in response to different plant pathogen in further studies.

PMID- 30278210
TI  - Long-term arsenite exposure induces testicular toxicity by redox imbalance, G2/M
      cell arrest and apoptosis in mice.
AB  - Inorganic arsenic (iAs), a ubiquitous element and a natural drinking water
      contaminant, has been found to impair male reproductive function. However, the
      effect of long-term exposure to arsenic on testis damage and its underlying
      mechanisms still require further evaluation. In the study, male C57BL/6 mice (4
      weeks) were treated with sodium arsenite at the doses of 5 or 50 ppm arsenic via
      drinking water for 180 days. Sperm count, histology in testes, oxidative stress
      biomarkers, cell cycle progress and apoptosis were assessed. Our results showed
      that arsenite seriously destroyed the structure of the testes and reduced the
      sperm count. Arsenite significantly decreased the activity of total superoxide
      dismutase (T-SOD) and glutathione (GSH) content but increased the levels of
      reactive oxygen species (ROS) and malondialdehyde (MDA) in testes. Furthermore,
      arsenite could induce G2/M phase arrest in testes, concurrent with a significant
      decrease in mRNA and protein levels of cdc2 and cyclin B1, the upregulation of p
      cdc2, and an increase in mRNA levels of p53 and p21. Arsenite induced testicular
      apoptosis with a significant increase in Bax mRNA and protein levels, especially
      the caspase-3 activation. Testicular toxicity of the high dose group was stronger
      than that of the low dose group. In conclusion, testicular toxicity due to long
      term exposure to arsenite may relate to oxidative damage, G2/M arrest and
      promoted apoptosis in the testes of mice, which contributed to the increased risk
      of spermatogenesis disorders and male infertility.

PMID- 30278211
TI  - Great Himalayan leaf-nosed bats modify vocalizations to communicate threat
      escalation during agonistic interactions.
AB  - Bats vocalize extensively within various social contexts. Nevertheless, studies
      of agonistic interactions, associating vocalizations signalling the emotional
      state of a caller with individual signatures during aggressive vocalizations
      remain scarce. Here, we examined whether male Great Himalayan leaf-nosed bats
      (Hipposideros armiger) modify their aggressive vocalizations during agonistic
      interactions depending on the level of aggression, and whether these
      vocalizations encode individual signatures. We applied a cost-benefit analysis to
      audio-video recordings of 50 dyadic agonistic interactions to categorize displays
      into two levels of aggression intensity (low aggression: bared teeth, slightly
      pulled up body and/or wings; high aggression: rapidly flapping wings, punching,
      biting). Male H. armiger used graded visual agonistic displays accompanied by
      bent upward frequency modulation (bUFM) vocalizations to defend their roosting
      territories. At high aggression intensities, males decreased the minimum
      frequency of aggressive calls and increased the frequency bandwidth. Males also
      transferred energy from the second harmonic to the first harmonic as the threat
      escalated. These systematic modifications of acoustic parameters as aggressive
      intensity fluctuated corresponded to prosodic modifications in human speech,
      indicating that emotion-related acoustic cues are a common feature of acoustic
      communication in mammals. In addition, we found that the aggressive calls of
      eight adult males encoded discriminable signatures, and that males could
      discriminate among individuals based on these aggressive calls. Such
      discrimination is probably useful for individual identification among rival
      neighbours.

PMID- 30278212
TI  - The reporting of safety among drug systematic reviews was poor before the
      implementation of the PRISMA harms checklist.
AB  - OBJECTIVES: To examine, through a cross-sectional survey, how well safety
      information was reported among drug systematic reviews predating PRISMA harms
      checklist and explore factors associated with better reporting. STUDY DESIGN AND
      SETTING: We searched PubMed to identify all systematic reviews published in the
      Cochrane Database of Systematic Review or the core clinical journals in 2015, one
      year before the PRISMA harms checklist was published. We randomly selected, in a
      1:1 ratio, Cochrane and non-Cochrane systematic reviews assessing drug effects
      (including both efficacy and safety). We used the PRISMA harms checklist
      published in 2016 to assess the quality of reporting of drug safety information.
      Multivariable linear regression analyses were used to explore the association of
      six prespecified variables with more complete reporting of PRISMA harms items.
      RESULTS: We included 120 systematic reviews, including 60 Cochrane and 60 non
      Cochrane reviews. Scores on the PRISMA harms checklist (23 items) were low
      (median 4, [first, third quartile: 2, 6]), with no difference between Cochrane
      and non-Cochrane reviews (4.5 [2, 7] vs. 4 [2.5, 5]; P = 0.29). Among all
      eligible reviews, only one item (i.e., state conclusions in coherence with the
      review findings) was reported adequately (proportion of adherence 81.6%);
      proportion of reporting for other items ranged from 1.7% to 68.3%. The four
      essential reporting items from PRISMA harms checklist were also poorly complied
      (proportion of adherence ranged from 1.7% to 9.2%). Multivariable linear
      regression analyses found no significant associations between any study
      characteristic and reporting on the PRISMA harms, likely because of limited
      variability in scores across studies. CONCLUSIONS: The reporting of safety
      information was poor both for Cochrane and non-Cochrane drug systematic reviews
      predating PRISMA harms checklist. The findings suggested a strong need to use the
      PRISMA harms checklist for reporting safety among drug systematic reviews.

PMID- 30278213
TI  - Tailored meta-analysis: an investigation of the correlation between the test
      positive rate and prevalence.
AB  - BACKGROUND: Meta-analysis may produce estimates that are unrepresentative of a
      test's performance in practice. Tailored meta-analysis (TMA) circumvents this by
      deriving an applicable region for the practice and selecting the studies
      compatible with the region. It requires the test positive rate, r and prevalence,
      p being estimated for the setting but previous studies have assumed their
      independence. The aim is to investigate the effects a correlation between r and p
      has on estimating the applicable region and how this affects TMA. METHOD: Six
      methods for estimating 99% confidence intervals (CI) for r and p were
      investigated: Wilson's +/- Bonferroni correction, Clopper-Pearson's +/-
      Bonferroni correction and Hotelling's T2 statistic +/- continuity correction.
      These were analysed in terms of the coverage probability using simulation trials
      over different correlations, sample sizes, and values for r and p. The methods
      were then applied to two published meta-analyses with associated practice data
      and the effects on the applicable region, studies selected and summary estimates
      evaluated. RESULTS: Hotelling's T2 statistic with a continuity correction had the
      highest median coverage (0.9971). This and the Clopper-Pearson method with a
      Bonferroni correction both had coverage consistently above 0.99. The coverage of
      Hotelling's CI's varied the least across different correlations. For both meta
      analyses, the number of studies selected was largest when Hotelling's T2
      statistic was used to derive the applicable region. In one instance this
      increased the sensitivity by over 4% compared with TMA estimates using other
      methods. CONCLUSION: TMA returns estimates which are tailored to practice
      providing the applicable region is accurately defined. This is most likely when
      the CI for r and p are estimated using Hotelling's T2 statistic with a continuity
      correction. Potentially, the applicable region may be obtained using routine
      electronic health data.

PMID- 30278214
TI  - Dual-calibrated fMRI measurement of absolute cerebral metabolic rate of oxygen
      consumption and effective oxygen diffusivity.
AB  - Dual-calibrated fMRI is a multi-parametric technique that allows for the
      quantification of the resting oxygen extraction fraction (OEF), the absolute rate
      of cerebral metabolic oxygen consumption (CMRO2), cerebral vascular reactivity
      (CVR) and baseline perfusion (CBF). It combines measurements of arterial spin
      labelling (ASL) and blood oxygenation level dependent (BOLD) signal changes
      during hypercapnic and hyperoxic gas challenges. Here we propose an extension to
      this methodology that permits the simultaneous quantification of the effective
      oxygen diffusivity of the capillary network (DC). The effective oxygen
      diffusivity has the scope to be an informative biomarker and useful adjunct to
      CMRO2, potentially providing a non-invasive metric of microvascular health, which
      is known to be disturbed in a range of neurological diseases. We demonstrate the
      new method in a cohort of healthy volunteers (n = 19) both at rest and during
      visual stimulation. The effective oxygen diffusivity was found to be highly
      correlated with CMRO2 during rest and activation, consistent with previous PET
      observations of a strong correlation between metabolic oxygen demand and
      effective diffusivity. The increase in effective diffusivity during functional
      activation was found to be consistent with previously reported increases in
      capillary blood volume, supporting the notion that measured oxygen diffusivity is
      sensitive to microvascular physiology.

PMID- 30278215
TI  - Longitudinal changes in serum vitamin D binding protein and free 25
      hydroxyvitamin D in a multiracial cohort of pregnant adolescents.
AB  - Serum free 25-hydroxyvitamin D (25(OH)D) rather than total 25(OH)D may better
      indicate vitamin D status during pregnancy given the pregnancy-associated
      increase in serum vitamin D binding protein (DBP) concentration. Our aims were to
      assess changes in DBP and free 25(OH)D across gestation and to determine whether
      free compared with total 25(OH)D more strongly correlates with markers of vitamin
      D and calcium metabolism during pregnancy. This ancillary study included 58
      pregnant adolescents (53% African American, 47% White) who completed a vitamin D3
      supplementation study in Rochester, NY. Blood was collected at entry, mid-study,
      and delivery (median 17, 29, and 40 weeks' gestation). Mixed-effects regression
      was used to test for differences in DBP, directly measured free 25(OH)D, and
      other serum markers by study visit and race. Free and total 25(OH)D were
      evaluated in relation to serum PTH, 1,25(OH)2D, 24,25(OH)2D, and calcium. The
      mean DBP concentration was above nonpregnant reference values at entry and
      increased across gestation (P < 0.0001). Total 25(OH)D explained most of the
      variance in free 25(OH)D (r >= 0.67; P < 0.0001). Holding total 25(OH)D constant,
      each 100 mg/L increase in DBP was associated with a 0.4 pg/mL decrease in free
      25(OH)D (P < 0.01). The percent free 25(OH)D was inversely related to both DBP
      and total 25(OH)D at each visit. Regardless of race or visit, total 25(OH)D was a
      stronger correlate of PTH, 1,25(OH)2D, and 24,25(OH)2D, and neither total nor
      free 25(OH)D was related to serum calcium. African Americans had lower total
      25(OH)D (P <  0.0001), but free 25(OH)D did not significantly differ by race (P =
      0.2). In pregnant adolescents, DBP concentration was elevated and inversely
      associated with percent free 25(OH)D, but measured free 25(OH)D provided no
      advantage over total 25(OH)D as a predictor of PTH, 1,25(OH)2D, 24,25(OH)2D, or
      calcium. The clinical relevance of the small racial difference in percent free
      25(OH)D requires further investigation.

PMID- 30278216
TI  - Ligand chirality can affect histidine protonation of vitamin-D receptor: ab
      initio molecular orbital calculations in water.
AB  - Vitamin D is recognized to play important roles in the onset of immunological
      diseases as well as the regulation of the amount of Ca in the blood. Since these
      physiological actions caused by active vitamin D are triggered by the specific
      interaction between the vitamin D receptor (VDR) and active vitamin D, many types
      of compounds have been developed as potent ligands against VDR. It was found that
      the binding affinity between VDR and its ligand depends significantly on the
      chirality of the ligand. However, the reason for the dependence has, thus far,
      not been elucidated. In the present study, we investigated the specific
      interactions between VDR and some ligands with different chirality, using ab
      initio fragment molecular orbital (FMO) calculations. The FMO results reveal that
      two histidine residues of VDR contribute significantly to the binding between VDR
      and ligand and that their protonation states can affect the specific interactions
      between VDR and ligand. We therefore considered other possible protonation states
      of these histidine residues and determined their most stable states, using the ab
      initio FMO calculations. The results illustrate the possibility that the
      difference in the chirality of a ligand can induce the change in protonation
      states of the histidine residues of VDR existing near the ligand. This finding
      provides an important warning that the protonation states of histidine residues
      existing near the ligand should be considered more precisely in the molecular
      simulations for investigating the specific interactions between protein and
      ligand.

PMID- 30278217
TI  - Bioimpedance analysis as an indicator of muscle mass and strength in a group of
      elderly subjects.
AB  - OBJECTIVE: To assess the association between whole-body and calf impedance
      vectors and muscle mass and strength in a group of elderly individuals. MATERIAL
      AND METHODS: We carried out a cross-sectional observational study on a sample of
      113 elderly people. Anthropometric parameters (weight, height and body
      circumferences) were determined. Body composition was evaluated using
      conventional bioimpedance analysis (BIA) and vector bioimpedance analysis (BIVA)
      (whole-body and calf BIVAs), and muscle strength was determined (manual
      dynamometry). The results were analyzed using the Student t-test or the Mann
      Whitney U, and the correlations using the Pearson or Spearman test. To compare
      BIVA results among the subgroups established, the Mahalanobis distance (dM) was
      calculated and the Hotelling T2 statistic was used. Statistical significance was
      set to p < 0.05. RESULTS: Nearly half the sample was overweight. Based on waist
      circumference, 66.7% of the males and 94.9% of the females showed risk of
      metabolic complications; calf circumference indicated no risk of disability or
      skeletal muscle mass depletion. However, BIA and dynamometry detected risk of
      sarcopenia in more than half the subjects. Whole-body BIVA results agreed with
      those of the BIA, given that most impedance vectors in both sexes were to the
      right of major axis of the tolerance ellipses. This shows cell mass depletion.
      While the whole-body BIVA distinguished the subjects having loss of muscle mass
      and strength, the specific BIVA (calf) only did so in individuals with muscle
      mass loss. CONCLUSIONS: Whole-body BIVA detects loss of muscle mass and strength,
      while calf BIVA only distinguishes subjects having muscle mass loss. The
      localized BIVA might be an alternative to conventional BIA or whole-body BIVA to
      assess body composition in the elderly.

PMID- 30278219
TI  - Prevalence, severity and explanatory factors of tooth wear in Arab populations.
AB  - OBJECTIVES: The aim of this study was to assess the prevalence and severity of
      tooth wear and related risk indicators in six Arab countries. METHODS: This
      multicenter, multinational cross-sectional study was conducted among 2924
      participants between the ages of 18-35 years old from six Arab countries.
      Calibrated dentists assessed tooth wear using the Basic Erosive Wear Examination
      Index (BEWE). Participants were also asked to complete a questionnaire that
      assessed their dietary and oral health habits. Each participant was identified by
      the sextant with the highest BEWE score in the upper and lower jaws. RESULTS:
      Odds ratios were estimated for correlates of tooth wear anterior and posterior
      regions. Oman had the highest prevalence of BEWE score 3 (N = 255 (60.2%)).
      Overall, the highest BEWE score 3 was observed on the incisal edge of the upper
      anterior teeth (N = 602 (20.6%)) and in the lower left posterior region (sextant
      6) on the occlusal surface (N = 466 (15.9%)). Correlates of severe tooth wear in
      both regions were eating or drinking more than six times per day, age and
      education. Drinking soft drinks "once a day" was significantly associated with
      severe tooth wear in the posterior region (OR: 1.3, 95% CI:1.05, 1.6). Brushing
      teeth more than twice a day was inversely associated with tooth wear in the
      anterior region (OR:0.75, 95% CI: 0.57,0.97). CONCLUSION: The prevalence of tooth
      wear in Arab populations is relatively high, specific preventive and therapeutic
      measures should be developed to target people at higher risk of this condition.
      CLINICAL SIGNIFICANCE: Tooth wear is now regarded as a significant oral health
      problems, dentists should advice their patients about dietary and oral health
      habits that can lead to severe tooth wear.

PMID- 30278220
TI  - White spot syndrome virus (WSSV) infection impacts intestinal microbiota
      composition and function in Litopenaeus vannamei.
AB  - Intestinal microbiota homeostasis is crucial to the health of host. Pathogen
      invasion results in dynamics of microbiota composition and structure, disrupting
      their function in maintaining host health. WSSV is the most prevalent viral
      pathogen and is able to cause extremely high mortality in Litopenaeus vannamei.
      However, the changes of intestinal microbiota induced by WSSV are yet to be
      elucidated. In this study, we analyzed and compared the microbiota of healthy and
      WSSV-challenged shrimp intestines. Though the richness and diversity of
      microbiota was barely affected by WSSV, the abundance of predominant phyla like
      Proteobacteria and Fusobacteria were upregulated significantly, while
      Bacteroidetes and Tenericutes were significantly decreased in WSSV-infected
      shrimps. At the genus level, significant increase was observed in Photobacterium,
      Propionigenium and Arcobacter, as well as significant decrease in Candidatus
      Bacilloplasma and Flavobacterium in WSSV-infected shrimps. Additionally,
      metagenomic predictions by PICRUSt suggested that the altered microbiota was
      mainly related to metabolism, human diseases, genetic information processing,
      environmental information processing and cellular processes. These results
      suggested that the invasion of WSSV could impact intestinal microbiota
      composition and function in L. vannamei.

PMID- 30278218
TI  - Sequence-based HLA-A, B, C, DP, DQ, and DR typing of 496 adults from San Diego,
      California, USA.
AB  - DNA sequence-based typing at the HLA-A, -B, -C, -DPB1, -DQA1, -DQB1, and -DRB1
      loci was performed on 496 healthy adult donors from San Diego, California, to
      characterize allele frequencies in support of studies of T cell responses to
      common allergens. Deviations from Hardy Weinberg proportions were detected at
      each locus except A and C. Several alleles were found in more than 15% of
      individuals, including the class II alleles DPB1*02:01, DPB1*04:01, DQA1*01:02,
      DQA1*05:01, DQB1*03:01, and the class I allele A*02:01. Genotype data will be
      available in the Allele Frequencies Net Database (AFND 3562).

PMID- 30278221
TI  - PARP inhibition in platinum-based chemotherapy: Chemopotentiation and
      neuroprotection.
AB  - Cisplatin, carboplatin and oxaliplatin represent the backbone of platinum therapy
      for several malignancies including head and neck, lung, colorectal, ovarian,
      breast, and genitourinary cancer. However, the efficacy of platinum-based drugs
      is often compromised by a plethora of severe toxicities including sensory and
      enteric neuropathy. Acute and chronic neurotoxicity following platinum
      chemotherapy is a major constraint, contributing to dose-reductions, treatment
      delays, and cessation of treatment. Identifying drugs that effectively prevent
      these toxic complications is imperative to improve the efficacy of anti-cancer
      treatment and patient quality of life. Oxidative stress and mitochondrial
      dysfunction have been highlighted as key players in the pathophysiology of
      platinum chemotherapy-induced neuropathy. Inhibition of poly(ADP-ribose)
      polymerase (PARP), a nuclear enzyme activated upon DNA damage, has demonstrated
      substantial sensory and enteric neuroprotective capacity when administered in
      combination with platinum chemotherapeutics. Furthermore, administration of PARP
      inhibitors alongside platinum chemotherapy has been found to significantly
      improve progression-free survival in patients with breast and ovarian cancer when
      compared to those receiving chemotherapy alone. This review summarises the
      current knowledge surrounding mitochondrial damage and oxidative stress in
      platinum chemotherapy-induced neuropathy and highlights a potential role for PARP
      in chemopotentiation and neuroprotection.

PMID- 30278222
TI  - Challenges in allergy immunology practice.

PMID- 30278223
TI  - Targeting intrinsically disordered proteins at the edge of chaos.
AB  - Intrinsically disordered proteins or intrinsically disordered regions (IDPs or
      IDRs) are those that do not fold into defined tertiary structures under
      physiological conditions. Given their prevalence in various diseases, IDPs are
      attractive therapeutic targets. However, because of the dynamic nature of the IDP
      structure, conventional structure-based drug design methods cannot be directly
      applied. Thanks to recent progress in understanding the mechanisms underlying IDP
      and ligand interactions, computational strategies for IDP-targeted rational drug
      discovery are emerging. Here, we summarize recent developments in computational
      IDP drug design strategies and their successful applications, analyze the typical
      properties of reported IDP-binding compounds (iIDPs), and discuss the major
      challenges ahead as well as possible solutions.

PMID- 30278224
TI  - Basic and practical concepts of radiopharmaceutical purification methods.
AB  - The presence of radiochemical impurities in a radiopharmaceutical contributes to
      an unnecessary radiation burden for the patients or to an undesirable high
      radioactivity background, which reduces the imaging contrast or therapeutic
      efficacy. Therefore, if the radiolabeling process results in unsatisfactory
      radiochemical purity, a purification step is unavoidable. A successful
      purification process requires a profound knowledge about the radiopharmaceuticals
      of interest ranging from structural features to susceptibility to different
      conditions. Most radiopharmaceutical purification methods are based on solid
      phase extraction (SPE), high-performance liquid chromatography (HPLC), size
      exclusion chromatography (SEC), ion-exchange chromatography (IEC), and liquid
      liquid extraction (LLE). Here, we discuss the basic and applied concepts of these
      purifications methods as well as their advantages and limitations.

PMID- 30278226
TI  - The Mediator complex and the role of protein-protein interactions in the gene
      regulation machinery.
AB  - At the core of gene regulation, a complex network of dynamic interactions between
      proteins, DNA and RNA has to be integrated in order to generate a binary
      biological output. Large protein complexes, called adaptors, transfer information
      from the transcription factors to the transcription machinery [1,2]. Here we
      focus on Mediator, one of the largest adaptor proteins in humans [3]. Assembled
      from 30 different subunits, this system provides extraordinary illustrations for
      the various roles played by protein-protein interactions. Recruitment of new
      subunits during evolution is an adaptive mechanism to the growing complexity of
      the organism. Integration of information happens at multiple scales, with
      allosteric effects at the level of individual subunits resulting in large
      conformational changes. Mediator is also rich in disordered regions that increase
      the potential for interactions by presenting a malleable surface to its
      environment. Potentially, 3000 transcription factors can interact with Mediator
      and so understanding the molecular mechanisms that support the processing of this
      overload of information is one of the great challenges in molecular biology.

PMID- 30278227
TI  - Hypoxia-induced autophagy promotes EGFR loss in specific cell contexts, which
      leads to cell death and enhanced radiosensitivity.
AB  - Treatment failure through radioresistance of tumors is associated with activation
      of the epidermal growth factor receptor (EGFR). Tumor cell proliferation, DNA
      repair, hypoxia and metastases-formation are four mechanisms in which EGFR
      signaling has an important role. However, the effect of hypoxia on EGFR
      expression is still controversial. In this study, we demonstrated that hypoxia
      enhanced EGFR expression and sustained cell survival in SiHa, CAL 27 and A549
      cells at both low and high cell desnities, while in MCF-7, MDA-MB-231 and HeLa
      cells, EGFR and cell survival were regulated by hypoxic treatment in a cell
      density dependent manner: upregulated at low cell density and downregulated at
      high cell density. In MCF-7 and HeLa xenografts in nude mice, EGFR expression
      varied inversely with the pimonidazole level that was used as an indicator of
      hypoxia, accordant with the effect of hypoxia at high cell density in vitro.
      Hypoxia induced more remarkable cell autophagy at high cell density than at low
      cell density. Autophagy inhibitor 3 MA, rather than proteasome inhibitor MG132
      inhibited hypoxia-mediated EGFR loss and shifted cell death to cell survival in
      HeLa cells. The MCF7 cells' sensitivity to ionizing radiation (IR) under hypoxia
      was also conditional on the cell densities when the hypoxia treatment was
      introduced, inversely associated with the expression levels of EGFR. Altogether,
      hypoxia can decrease EGFR expression in some cell lines by enhancing autophagy at
      high cell density, leading to cell death and hypersensitivity to radiotherapy.
      This study may help to understand how hypoxia influences EGFR expression and
      radiosensitivity.

PMID- 30278225
TI  - Ubiquitin-dependent protein degradation at the endoplasmic reticulum and nuclear
      envelope.
AB  - Numerous nascent proteins undergo folding and maturation within the luminal and
      membrane compartments of the endoplasmic reticulum (ER). Despite the presence of
      various factors in the ER that promote protein folding, many proteins fail to
      properly fold and assemble and are subsequently degraded. Regulatory proteins in
      the ER also undergo degradation in a way that is responsive to stimuli or the
      changing needs of the cell. As in most cellular compartments, the ubiquitin
      proteasome system (UPS) is responsible for the majority of the degradation at the
      ER-in a process termed ER-associated degradation (ERAD). Autophagic processes
      utilizing ubiquitin-like protein-conjugating systems also play roles in protein
      degradation at the ER. The ER is continuous with the nuclear envelope (NE), which
      consists of the outer nuclear membrane (ONM) and inner nuclear membrane (INM).
      While ERAD is known also to occur at the NE, only some of the ERAD ubiquitin
      ligation pathways function at the INM. Protein degradation machineries in the
      ER/NE target a wide variety of substrates in multiple cellular compartments,
      including the cytoplasm, nucleoplasm, ER lumen, ER membrane, and the NE. Here, we
      review the protein degradation machineries of the ER and NE and the underlying
      mechanisms dictating recognition and processing of substrates by these
      machineries.

PMID- 30278228
TI  - Can pediatricians provide long acting reversible contraception?
AB  - STUDY OBJECTIVES: In the US, 40% of high-school students have sex; few use highly
      effective and safe long-acting reversible contraceptives (LARCs): intrauterine
      devices (IUDs) and implants. Pediatricians are key health providers for many
      adolescents, yet few provide LARC. Our objective was to understand the pragmatics
      of provision of LARC (rather than beliefs or attitudes) and identify barriers to
      and opportunities for LARC provision by community-practicing pediatricians.
      DESIGN: We conducted a qualitative descriptive study with semi-structured
      interviews; qualitative methods are valuable for generating conceptual models of
      complex phenomena. SETTING: Set in a mid-sized Midwestern city, our study was
      community-based. PARTICIPANTS: We interviewed 23 pediatricians to understand
      their views about providing contraception (including LARC) to adolescents. For
      analysis, we developed a coding schema and applied it using a priori and open
      coding. RESULTS: Several interrelated themes regarding challenges to provision of
      LARC emerged: limited motivation for onsite LARC provision or referral streams,
      low pediatric patient interest in LARC, lack of pediatrician training about LARC
      provision, and inadequate structural elements for onsite placement of LARC in
      pediatric offices. Each challenge could be remedied, as pediatricians were
      motivated to provide adolescent patients with high quality care. Improvements in
      these interrelated conditions could facilitate pediatrician provision of LARC.
      CONCLUSION: Pediatricians and their patients want to prevent pregnancy, but
      current practice norms limit LARC provision by pediatricians. To increase LARC
      access in pediatrician offices, we suggest training in LARC provision and patient
      education for medical students, residents, and pediatricians; communicating about
      LARC methods with adolescents to increase patient demand; and systemic changes to
      improve referral processes and/or allow on-site LARC placements.

PMID- 30278229
TI  - Burkitt Lymphoma Presenting as Menorrhagia and a Vaginal Mass in an Adolescent.
AB  - BACKGROUND: Menorrhagia is a common gynecologic complaint among adolescents,
      which rarely is secondary to malignancy. Burkitt lymphoma can mimic gynecologic
      malignancy, however it is rarely seen in adolescents. Burkitt lymphoma of the
      gynecologic tract requires early diagnosis and intervention for optimal outcomes.
      CASE: We report a case of a 15-year-old adolescent who had multiple admissions
      for menorrhagia that was thought to be secondary to anovulatory bleeding until
      pelvic ultrasound revealed a large 8-cm vaginal/cervical mass. Histologic
      examination of the biopsy specimen revealed Burkitt lymphoma, which was treated
      with chemotherapy leading to resolution of her menorrhagia. SUMMARY AND
      CONCLUSION: Burkitt lymphoma presenting as a vaginal/cervical mass is exceedingly
      rare, especially in the adolescent patient. Burkitt lymphoma is generally highly
      responsive to chemotherapy, and symptoms rapidly improve after initiation of
      treatment.

PMID- 30278230
TI  - Recommendations for the use of Electrophysiological Study: Update 2018.
AB  - The field of cardiac electrophysiology has greatly developed over the past
      decades. As a consequence, the use of electrophysiological studies (EPS) in
      clinical practice has also significantly augmented, with a progressively
      increasing number of certified electrophysiology centers and specialists. Since
      Zipes et al published the Guidelines for Clinical Intracardiac Electrophysiology
      and Catheter Ablation Procedures in 1995, no official document summarizing
      current EPS indications has been published.

PMID- 30278231
TI  - Mechanisms of isolevuglandin-protein adduct formation in inflammation and
      hypertension.
AB  - Inflammation has been implicated in the pathogenesis of hypertension and recent
      evidence suggests that isolevuglandin (IsoLG)-protein adducts play a role.
      Several hypertensive stimuli contribute to formation of IsoLG-protein adducts
      including excess dietary salt and catecholamines. The precise intracellular
      mechanisms by which these hypertensive stimuli lead to IsoLG-protein adduct
      formation are still not well understood; however, there is now evidence
      implicating NADPH-oxidase derived reactive oxygen species (ROS) in this process.
      ROS oxidize arachidonic acid leading to formation of IsoLGs, which non-covalently
      adduct to lysine residues and alter protein structure and function. Recent
      studies suggest that these altered proteins act as neo-antigens leading to an
      autoimmune state that results in hypertension. The goal of this mini-review is to
      highlight some of the hypertensive stimuli and the mechanisms contributing to
      IsoLG-protein adduct formation leading to inflammation and hypertension.

PMID- 30278232
TI  - The Non-Avoidant Pacing Scale: Development and Preliminary Validation.
AB  - Despite widespread use as a chronic pain management strategy, pacing has been
      linked with higher levels of pain and disability. A recent meta-analysis found a
      positive correlation between existing measures of pacing and avoidance, which may
      partially account for these poorer outcomes. A measure was developed to
      differentiate pacing from avoidance by emphasizing non-pain-contingent pacing
      behaviors and nonavoidance of pain. A sample of 283 adults with chronic pain
      completed the Non-Avoidant Pacing Scale (NAPS) and existing measures of pacing,
      avoidance, pain, and physical and psychological functioning. Exploratory factor
      analysis of 10 items (subsample 1, n = 141) suggested two 4-item factors: planned
      pacing behaviors and pacing through flare ups. Confirmatory factor analysis of 8
      items (subsample 2, n = 142) revealed satisfactory fit (goodness-of-fit index
      .947, comparative fit index .964). The pattern of correlations between each
      factor and avoidance and key outcomes suggests that the NAPS total scale (alpha =
      .819) captures key pacing behaviors and differentiates pacing from avoidance.
      Unlike existing measures, the NAPS was not positively correlated with avoidance
      and was associated with better psychological functioning across affective and
      cognitive domains. The NAPS allows researchers and clinicians to assess the role
      of pacing in chronic pain management without artefactual overlap with avoidance.
      PERSPECTIVE: The NAPS assesses activity pacing in chronic pain without
      artefactual overlap with avoidance. Associations were found between more frequent
      pacing, as measured by the NAPS, and better psychological functioning. Clearly
      differentiating pacing from avoidance allows for accurate assessment of the role
      of pacing in chronic pain management.

PMID- 30278233
TI  - Laparoendoscopic Single-site Surgery for Comprehensive Staging of Early Ovarian
      Cancer.
AB  - STUDY OBJECTIVE: To demonstrate the procedure and suspension skills of
      laparoendoscopic single-site (LESS) staging surgery with infrarenal para-aortic
      lymphadenectomy for early-stage ovarian cancer. DESIGN: A presentation of the
      surgery through this technical video. SETTING: A hospital. PATIENT AND
      INTERVENTIONS: A 45-year-old woman presented with a pelvic mass on gynecologic
      examination and a serum cancer antigen 125 level of 5910 U/mL (normal = <35
      U/mL). A computed tomographic scan revealed a mixture of solid and cystic
      components (70 * 77 * 71 mm) arising from the right ovary and characterized by
      the "ovarian vascular pelvic" sign. Clinically early-stage ovarian cancer was
      suspected. Subsequently, LESS staging surgery was performed by an experienced
      surgeon in our department. RESULTS: The surgery lasted 280 minutes, and the
      volume of blood loss was 50 mL; there were no intra- or postoperative
      complications. We "hid" the incision perfectly for cosmetic purposes. The
      histopathologic findings supported high-grade serous ovarian cancer of the right
      ovary with the left fallopian tube involved as well. In addition, a total of 34
      negative pelvic and 18 negative para-aortic lymph nodes were identified, and a
      stage of IIA was diagnosed as a result. CONCLUSION: We performed an LESS staging
      surgery for early-stage ovarian cancer successfully. Our video shows that the
      LESS approach provided feasible, cosmetic, and safe access among the selected
      malignant gynecologic surgery. Therefore, we have experienced that the effective
      suspension was an auxiliary measure for LESS lymphadenectomy. In addition,
      compared with multiport laparoscopy, the LESS approach could provide easier
      access to infrarenal para-aortic regions; furthermore, it was safe and quick to
      extract an unknown sample.

PMID- 30278234
TI  - Bladder Endometriosis: Management by Cystoscopic and Laparoscopic Approaches.
AB  - STUDY OBJECTIVE: Endometriosis of the urinary system accounts for less than 1% of
      all endometriosis, wherein bladder endometriosis is the most common. Bladder
      endometriosis is defined as endometriosis infiltrating the detrusor muscle and
      represents 85% of urinary tract endometriosis [1,2]. Segmental bladder
      resection/partial cystectomy is the bladder-preserving surgery and offers the
      complete removal of bladder endometriotic nodules [3,4]. Laparoscopic/robotic
      excision increases the chances of complete removal of nodules but may lead to
      inadvertent removal of excess bladder wall and increase the risk of
      complications, especially in cases of large lesions in close proximity to
      ureteric orifices. Thus, simultaneous laparoscopy and cystoscopy offers the most
      effective way of complete resection of bladder endometriotic nodules, relieving
      symptoms and minimizing intraoperative and postoperative complications and
      recurrence rates in patients [5-11]. This article with accompanying video
      describes the systematic approach and step-by-step surgical excision of a bladder
      endometriotic nodule in a patient with frozen pelvis. DESIGN: Step-by-step
      surgical excision of a bladder endometriotic nodule by simultaneous cystoscopy
      and laparoscopy. (Canadain Task Force classification: level III) SETTING: Jyoti
      Hospital and Minimum Invasive Surgery Center, Ahmedabad, India. PATIENT: A 41
      year-old women, P2L2, presented with cyclical dysmenorrhea, dysuria, and chronic
      pelvic pain. Informed consent was obtained from the patient, and the local
      institutional board provided the approval. INTERVENTION: Simultaneous cystoscopy
      and laparoscopy. MEASUREMENTS AND MAIN RESULTS: A preoperative assessment was
      done with transvaginal ultrasonography with a partially full bladder that showed
      an intravesical 3-cm endometriotic nodule along with chocolate cysts of the ovary
      and adenomyosis of the uterus. A simultaneous cystoscopy by a urologist and
      laparoscopy by a gynecologist was performed. On cystoscopy the nodule was seen
      away from both the ureteric orifices. The nodule was marked cystoscopically with
      a monopolar needle and laparoscopically with bipolar scissors. Laparoscopy began
      with a full inspection of the abdomen, pelvis, and adhesions. Dissection started
      from the left round ligament, and both paravesical spaces were dissected gently,
      keeping the bladder partially full. Good uterine manipulation helped to delineate
      vaginal fornices during dissection. Dissection continued over the isthmus, and
      bladder was gently separated from the isthmus. The bladder was partially filled
      with methylene blue and intentionally cut opened to excise the demarcated bladder
      nodule with a monopolar hook, taking a disease-free margin of 5 mm [12]. Two stay
      sutures were taken at both the lateral angles of the bladder, and suture ends
      were brought outside the abdomen to facilitate closure of the bladder
      transversely. After mobilization of the bladder, both uterine vascular bundles
      were desiccated with bipolar and laparoscopic hysterectomy. Vaginal closure was
      done away from bladder stitches. The patient was discharged on day 3 with
      catheter and DJ stents. On day 21, 3-dimensional computed tomography cystogram
      showed adequate bladder volume. Catheter and DJ stents were removed, low-pressure
      cystoscopy showed a smooth stitch line with mucosa over it and no residual
      endometriosis. The patient was found to have no symptoms at the 2-year follow up.
      CONCLUSION: The video demonstrates the feasibility of simultaneous laparoscopic
      and cystoscopic approach for excision of a bladder endometriotic nodule. Marking
      the nodule by simultaneous cystoscopy and laparoscopy before excision helps in
      removing the disease completely and avoiding unnecessary normal bladder wall
      excision, thus reducing the risk of recurrence and resultant small bladder
      symptoms.

PMID- 30278235
TI  - WITHDRAWN: Author's Reply.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 30278236
TI  - Regarding [Hemostatic Techniques for Myomectomy: An Evidence-Based Approach].

PMID- 30278237
TI  - Disease-related outcomes influence prevalence of falls in people with rheumatoid
      arthritis.
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of
      falls, with potential adverse outcomes. There is a considerable variation across
      studies regarding the prevalence of falls and its correlation with clinical data,
      disease-related outcomes and physical performance tests. OBJECTIVE: The aim of
      this study was to evaluate the prevalence of falls and its association with
      clinical data, disease-related outcomes and physical performance tests. METHODS:
      In this cross-sectional study, 113 RA patients were divided into 3 groups - "non
      fallers", "sporadic fallers" and "recurrent fallers" - and compared in terms of
      clinical data, Clinical Disease Activity Index (CDAI), lower-limb tender and
      swollen joint count, disability (Health Assessment Questionnaire-Disability Index
      [HAQ-DI]), Foot Function Index (FFI), Berg Balance Scale (BBS), Timed-up-and-go
      Test (TUG) and 5-Time Sit Down-To-Stand Up Test (SST5). Logistic regression
      analysis was performed to analyze the associations between the studied variables
      and the occurrence of falls, estimating odds ratios (ORs). We also analyzed the
      correlation between disease outcome measures (HAQ-DI and CDAI) and physical tests
      (BBS, TUG, SST5). RESULTS: Falls and fear of falling were reported by 59 (52.21%)
      and 71 (64.5%) patients, respectively. Significant associations were found
      between "recurrent fallers" and vertigo (OR=3.42; P=0.03), fear of falling
      (OR=3.44; P=0.01), low income (OR=2.02; P=0.04), CDAI (OR=1.08; P<0.01), HAQ-DI
      (OR=3.66; P<0.01), Lower-limb HAQ (OR=3.48; P<0.01), FFI-pain (OR=1.24; P=0.03),
      FFI-total (OR=1.23; P=0.04), lower-limb tender joint count (OR=1.22; P<0.01), BBS
      score (OR=1.14; P<0.01), TUG score (OR=1.13; P=0.03) and SST5 score (OR=1.06;
      P=0.02). On multivariate analysis, CDAI was the only significant predictor of
      recurrent falls (OR=1.08; P<0.01). Physical performance test scores (BBS, TUG,
      SST5) were correlated with the CDAI and HAQ-DI. CONCLUSION: The prevalence of
      falls in RA is high, most influenced by disease-related outcomes and linked to
      worse performance on physical tests (BBS, TUG and SST5).

PMID- 30278238
TI  - Are probiotics and prebiotics effective in the prevention of travellers'
      diarrhea: A systematic review and meta-analysis.
AB  - BACKGROUND: Travellers' diarrhea (TD) impacts annually over 20 million tourists,
      business travellers and military troops on a worldwide basis. Reliance on
      antibiotic prophylaxis and educational programs has not lead to a significant
      reduction in TD rates. Previous reviews of probiotics for TD have not accounted
      for the strain-specificity of probiotic efficacy nor have investigated prebiotics
      for the prevention of TD. METHODS: Standard literature databases were searched
      from 1977 to June 2018 unrestricted by language. Inclusion criteria included:
      Probiotic, probiotic or symbiotic interventions, randomized, controlled clinical
      trials (RCTs) and >=2 RCTs with the same probiotic strain or mixture. RESULTS: Of
      158 screened articles, 12 RCT were included in the systematic review and 6 RCTs
      (with nine treatment different arms) were included in the meta-analysis.
      Saccharomyces boulardii CNCM I-745 showed a significant reduction in TD incidence
      (RR = 0.79, 95% C.I. 0.72-0.87, p < 0.001), while L. rhamnosus GG showed a trend
      (p = 0.08) and L. acidophilus showed no significant (p = 0.16) reduction of TD.
      CONCLUSIONS: The number of trials using probiotics or prebiotics for the
      prevention of TD continues to be limited in number. Only one of three probiotics
      showed significant efficacy for the prevention of TD. More research is needed for
      other probiotics strains and prebiotics to determine if they could also prevent
      TD.

PMID- 30278239
TI  - Modulating alpha-synuclein fibril formation using DNA tetrahedron nanostructures.
AB  - The small presynaptic protein alpha-synuclein (alpha-syn) is involved in the
      etiology of Parkinson's disease owing to its abnormal misfolding. To date, little
      information is known on the role of DNA nanostructures in the formation of alpha
      syn amyloid fibrils. Here, the effects of DNA tetrahedrons on the formation of
      alpha-syn amyloid fibrils were investigated using various biochemical and
      biophysical methods such as thioflavin T fluorescence assay, atomic force
      microscopy, light scattering, transmission electron microscopy, and cell-based
      cytotoxicity assay. It has been shown that DNA tetrahedrons decreased the level
      of oligomers and increased the level of amyloid fibrils, which corresponded to
      decreased cellular toxicity. The ability of DNA tetrahedron to facilitate the
      formation of alpha-syn amyloid fibrils demonstrated that structured nucleic acids
      such as DNA tetrahedrons could modulate the process of amyloid fibril formation.
      Our study suggests that DNA tetrahedrons could be used as an important
      facilitator toward amyloid fibril formation of alpha-synuclein, which may be of
      significance in finding therapeutic approaches to Parkinson's disease and related
      synucleinopathies.

PMID- 30278240
TI  - Is CYP1B1 involved in the metabolism of dioxins in the pig?
AB  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most difficult to biodegradate
      and the most toxic dioxin congener. Previously, we demonstrated in silico the
      ability of pig CYP1A1 to hydroxylate 2,7-dichlorodibenzo-p-dioxin (DiCDD), but
      not TCDD. To increase our knowledge concerning the low effectiveness of TCDD
      biodegradability, we analyzed in silico the binding selectivity and affinity
      between pig CYP1B1 and the two dioxins by means of molecular modeling. We also
      compared the effects of TCDD and DiCDD on CYP1B1 gene expression (qRT-PCR) and
      catalytic (EROD) activity in porcine granulosa cells. It was found that DiCDD and
      TCDD were stabilized within the pig CYP1B1 active site by hydrophobic
      interactions. The analysis of substrate channel availability revealed that both
      dioxins opened the exit channel S, allowing metabolites to leave the enzyme
      active site. Moreover, DiCDD and TCDD increased the CYP1B1 gene expression and
      catalytic activity in porcine granulosa cells. On the other hand, TCDD
      demonstrated higher than DiCDD calculated affinity to pig CYP1B1, hindering TCDD
      exit from the active site. The great distance between CYP1B1's heme and TCDD also
      might contribute to the lower hydroxylation effectiveness of TCDD compared to
      that of DiCDD. Moreover, the narrow active site of pig CYP1B1 may immobilize TCDD
      molecule, inhibiting its hydroxylation. The results of the access channel
      analysis and the distance from pig CYP1B1's heme to TCDD suggest that the
      metabolizing potential of pig CYP1B1 is higher than that of pig CYP1A1. However,
      this potential is probably not sufficiently high to considerably improve the slow
      TCDD biodegradation.

PMID- 30278241
TI  - Insulin-like growth factor type I selectively binds to G-quadruplex structures.
AB  - BACKGROUND: G-quadruplex has been viewed as a promising therapeutic target in
      oncology due to its potentially important roles in physiological and pathological
      processes. Emerging evidence suggests that the biological functions of G
      quadruplexes are closely related to the binding of some proteins. Insulin-like
      growth factor type I (IGF-1), as a significant modulator of cell growth and
      development, may serve as a quadruplex-binding protein. METHODS: The binding
      affinity and selectivity of IGF-1 to different DNA motifs in solution were
      measured by using fluorescence spectroscopy, Surface Plasmon Resonance (SPR), and
      force-induced remnant magnetization (FIRM). The effects of IGF-1 on the formation
      and stability of G-quadruplex structures were evaluated by circular dichroism
      (CD) and melting fluorescence resonance energy transfer (FRET) spectroscopy. The
      influence of quadruplex-specific ligands on the binding of G-quadruplexes with
      IGF-1 was determined by FIRM. RESULTS: IGF-1 shows a binding specificity for G
      quadruplex structures, especially the G-quadruplex structure with a parallel
      topology. The quadruplex-specific ligands TMPyP4 and PDS (Pyridostatin) can
      inhibit the interaction between G-quadruplexes and proteins. CONCLUSIONS: IGF-1
      is demonstrated to selectively bind with G-quadruplex structures. The use of
      quadruplex-interactive ligands could modulate the binding of IGF-1 to G
      quadruplexes. GENERAL SIGNIFICANCE: This study provides us with a new perspective
      to understand the possible physiological relationship between IGF-1 and G
      quadruplexes and also conveys a strategy to regulate the interaction between G
      quadruplex DNA and proteins.

PMID- 30278242
TI  - Metabolism and disposition of arsenic species from controlled dosing with sodium
      arsenite in adult female CD-1 mice. III. Toxicokinetic studies following oral and
      intravenous administration.
AB  - Arsenic is a ubiquitous contaminant, with typical dietary intake below 1 MUg/kg
      bw/d and drinking water exposures up to 50 MUg/kg bw/d. Arsenic exposures are
      associated with human diseases and doses of toxicological concern are similar to
      typical dietary intake. Metabolism of arsenite to dimethylarsinate (DMAV) by
      arsenite-3-methyltransferase (As3MT) promotes clearance, but also generates
      reactive trivalent intermediates that bind extensively to cellular thiols. This
      study measured pentavalent and trivalent arsenic species in blood and tissues
      after oral and intravenous administration of arsenite (50 MUg/kg bw). After oral
      administration, the intestine and liver contained elevated levels of AsIII and
      MMAIII, relative to erythrocytes, lung, and kidney, suggesting incomplete
      conversion to DMA during first-pass metabolism. However, blood concentrations of
      the predominant species, DMA, were similar for oral and intravenous dosing. While
      all tissues examined contained DMAIII, muscle, brain, and plasma had undetectable
      levels of MMAIII. Tissue levels of arsenic species were similar following
      intravenous vs. oral administration, except lower in the intestine. The results
      confirm the role of metabolism in producing fluxes of putatively toxic trivalent
      arsenic intermediates. Tissue dosimetry suggests that the intestine, liver, lung,
      and kidney could be more susceptible to effects of bound arsenic, relative to
      muscle and brain.

PMID- 30278243
TI  - Preliminary assessment of galaxolide bioaccessibility in raw and cooked FISH.
AB  - Generally, dietary intake assessment and risk characterization are evaluated
      using contaminant concentration in raw fish while it is usually ingested cooked,
      which can cause an overestimation because one of the essential issues for risk
      benefit analysis is to determine the maximum amount of a contaminant that can be
      released from the food matrix and be absorbed by the human body, called
      bioaccessibility. Moreover, despite most seafood products are cooked before
      consumption, risk assessment is still evaluated in raw products, strongly
      affecting public health guidelines. In the present study, an in vitro
      bioaccessibility assay was performed for Galaxolide (HHCB) in fish samples. Raw
      spiked hake samples were in vitro digested and aliquots of each fraction of the
      digestion process were analysed. HHCB was quantitatively present in the
      bioaccessibility fraction. The effect of fish cooking on HHCB was also evaluated
      in cod and mackerel samples. Results demonstrate that steaming and grilling
      processes lead to a loss of 50-70% HHCB in fish.

PMID- 30278244
TI  - Postnatal exposure to chlorpyrifos produces long-term effects on spatial memory
      and the cholinergic system in mice in a sex- and APOE genotype-dependent manner.
AB  - Organophosphorus pesticides - and in particular chlorpyrifos (CPF) - are
      extensively used worldwide. They mainly exert their toxicity by targeting the
      cholinergic system. Several studies suggested that the gene coding for
      apolipoprotein E (apoE), which is a risk factor for several diseases, can also
      confer different vulnerability to toxic insults. This study was aimed at
      assessing the long-term effects of postnatal exposure to CPF on learning and
      memory as well as the expression levels of several genes involved in cholinergic
      neurotransmission in mice. Both male and female apoE4-TR and C57BL/6 mice were
      exposed to either 0 or 1 mg/kg/day of CPF by oral gavage using a micropipette on
      postnatal days 10-15. At 9 months, they were tested in a Morris Water Maze (MWM)
      and the gene expression in the frontal cortex and hippocampus was evaluated. Our
      results show that, in males, CPF had an effect on the spatial retention, while in
      females, it altered the expression levels of nicotinic receptors. Furthermore,
      apoE4-TR mice performed the worst during the MWM retention and presented low
      expression levels in a considerable number of cholinergic genes. Taken together,
      the current results reveal long-term effects in mice nine months after postnatal
      exposure to CPF, which are modulated by sex and apoE4 genotype.

PMID- 30278245
TI  - Depression-like behaviors induced by chronic corticosterone exposure via drinking
      water: Time-course analysis.
AB  - Hypothalamic-pituitary-adrenal (HPA) axis activity is commonly dysregulated in
      stress-related psychiatric disorders. The corticosterone rat model was developed
      to understand the influence of stress on depression-like symptomatology. To
      further understand the effects of corticosterone on the development of depression
      like behavior, rats were continuously exposed to corticosterone (200 MUg/ml) or
      vehicle via drinking water daily for 21 days. The rats underwent a series of
      behavioral tests, and electroencephalographical recordings were performed after
      7, 14, and 21 days of treatment. The measurements included immobility time (i.e.,
      despair) in the forced swim test, locomotor activity in the open field test,
      sucrose consumption (i.e., anhedonia) in the sucrose preference test, and sleep
      wake parameters. The rats in the 7-day corticosterone exposure group exhibited
      depression-like behavior, including increases in despair, anhedonia, anxiety, and
      sleep impairments. The rats in the 14-day corticosterone exposure group exhibited
      normal patterns of behavior and sleep structure. When corticosterone exposure was
      extended to 21 days, depression-like symptoms recurred, including despair,
      anhedonia, anxiety, and sleep disturbances. Overall, the present study observed U
      shaped depression-like effects across 3 weeks of corticosterone exposure via
      drinking water.

PMID- 30278246
TI  - Effect of 5-HT2A receptor antagonist ketanserin on micturition in male rats.
AB  - OBJECTIVES: This study aimed to investigate the effects of ketanserin on
      micturition mediated via the 5-HT2A receptor in the motoneuron nucleus of the
      Lumbosacral cord, as reflected in high frequency oscillations (HFOs) of
      intravesical pressure and the external urethral sphincter electromyogram (EUS
      EMG) in anesthetized male rats. METHODS:: Male Sprague-Dawley rats were used.
      Cystometry and EUS-EMG were performed in all rats under urethane anesthesia to
      examine the variations after successive intrathecal (i.t.) administration of
      various doses of ketanserin into the lumbosacral cord. Immunofluorescence
      staining and Western blotting were made to observe the distribution of 5-HT2 A
      and -2C receptors in the lumbosacral cord motor neurons. RESULTS: Compared to the
      controls, ketanserin-treated rats showed a declined trend of dose-dependent
      manner in the HFOs, in accordance with the variation of EUS-EMG, while decreased
      micturition volume, voiding efficiency, and increased post-void residual volume
      was only observed at the dose of 0.1 mg/kg. The effects of ketanserin on the HFO
      and EUS-EMG activity were partially or completely reversed by the 5-HT2A/2C
      receptor agonist, DOI. Meanwhile, immunofluorescence staining and Western blot
      analysis showed that immunoreactivity of 5-HT2A receptor was higher than that of
      5-HT2C, labeling in the lumbosacral cord motoneurons. CONCLUSIONS: The
      intrathecally administrated 5-HT2A receptor antagonist ketanserin can weaken the
      EUS bursting activity, decrease HFOs, and reduce voiding efficiency as dose
      dependently. The effects of ketanserin on micturition may be mainly mediated via
      the 5-HT2A receptors in the motoneuron nucleus of the lumbosacral cord.

PMID- 30278247
TI  - Association of vascular endothelial growth factor levels in CSF and cerebral
      glucose metabolism across the Alzheimer's disease spectrum.
AB  - The association of vascular endothelial growth factor (VEGF) levels in CSF and
      cerebral glucose metabolism across the Alzheimer's disease (AD) spectrum is
      unclear. CSF VEGF levels were cross-sectionally related to cerebral glucose
      metabolism, as measured by 18F-fluorodeoxyglucose positron emission tomography
      (FDG-PET), using linear regression models. We found that VEGF levels were
      associated with cerebral glucose metabolism in patients with mild cognitive
      impairment (MCI) and AD, but not in cognitively normal older adults. Our data
      indicated that VEGF may play an important role in cerebral glucose metabolism.

PMID- 30278248
TI  - Anti-neuroinflammatory effects of SLOH in Abeta-induced BV-2 microglial cells and
      3xTg-AD mice involve the inhibition of GSK-3beta.
AB  - Neuroinflammation has been observed in post-mortem Alzheimer's disease (AD)
      brains which could be due to Abeta interacting with microglia and astrocytes.
      SLOH, a carbazole-based fluorophore, was shown to bind to Abeta peptides. Herein,
      we investigated the anti-neuroinflammatory effects of SLOH using a BV-2
      microglial cell model and a triple transgenic AD (3xTg-AD) mouse model. BV-2
      cells were incubated with Abeta in the presence of SLOH for 24 h. The levels of
      pro-inflammatory and anti-inflammatory cytokines were determined. Moreover, 3xTg
      AD mice were administrated with SLOH (2 mg kg-1) for one month. The mice were
      then sacrificed and the brains were used to assess the levels of pro
      inflammatory, anti-inflammatory cytokines and the activation of ionized calcium
      binding adapter molecule 1 (Iba1). BV-2 cell studies suggested that SLOH reduced
      the production and mRNA levels of pro-inflammatory cytokines TNF-alpha, IL-1beta,
      COX-2, iNOS, and increased IL-10. Animal study confirmed that SLOH reduced the
      production of pro-inflammatory cytokines and increased the level of anti
      inflammatory cytokine. Moreover, SLOH inhibited the activity of GSK-3beta. In
      3xTg-AD mouse model, SLOH treatment significantly decreased the number of Iba1
      positive cells in mouse brains. Our results demonstrated that SLOH significantly
      attenuated the neuroinflammation through down-regulating the activity of GSK
      3beta.

PMID- 30278250
TI  - Remaining Puzzles about Morpheme Production in the Posterior Temporal Lobe.
AB  - Using data from time-resolved cortical stimulation, intracranial neural
      recordings, and focal surgical resections, Lee et al. (2018) demonstrate that a
      small area within left posterior superior temporal gyrus (pSTG) supports the
      ability to produce functional morphemes but not other basic aspects of language
      production or comprehension. These findings are intriguing because they raise
      important questions about the functional architecture of language processing,
      including critically, the relationship between production and comprehension.
      Here, we highlight some of the puzzles that remain and that we hope will guide
      future empirical explorations of the cognitive and neural mechanisms that support
      our capacity for language.

PMID- 30278249
TI  - Diffusion Kurtosis Imaging Characterizes Brain Microstructural Changes Associated
      with Cognitive Impairment in a Rat Model of Chronic Traumatic Brain Injury.
AB  - This study aims to investigate the value of diffusion kurtosis imaging (DKI) in
      assessing microstructural changes associated with cognitive impairment in chronic
      traumatic brain injury (TBI). At 7 months, six TBI rats and six control rats
      underwent Morris water maze (MWM) tests, followed by DKI examinations. DKI
      parameters were measured in bilateral cortex, hippocampus, and callosum. Brain
      immunohistochemistry (IHC) analysis of neuron [neuron-specific nuclear protein
      (NeuN)], astroglia [glial fibrillary acidic protein (GFAP)], microglia [ionized
      calcium binding adaptor molecule 1 (Iba-1)], and myelin [myelin basic protein
      (MBP)] was performed in the same area as DKI parameter. The DKI parameters, IHC
      results, and MWM results were compared between TBI and control groups.
      Correlation analysis was performed to analyze the relationship between DKI
      parameters and IHC and MWM results. TBI group had worse performance in MWM test.
      DKI showed higher mean diffusion (MD) in all ipsilateral regions of interest
      (ROIs), and lower mean kurtosis (MK) in ipsilateral cortex and callosum in TBI
      group (P < 0.05). TBI group also showed lower IHC staining of NeuN, and higher
      staining of Iba-1 and MBP in all ipsilateral ROIs (P < 0.05). Further
      correlational study showed a positive relationship between MK and NeuN, MD and
      MBP in ipsilateral cortex, and a negative relationship between MK and Iba-1, MBP
      in ipsilateral cortex and hippocampus (P < 0.05). The MK in ipsilateral cortex
      and hippocampus were also correlated with MWM test results (P < 0.05). Our study
      suggests that DKI could be used to assess the microstructural changes associated
      with cognitive impairment in chronic TBI.

PMID- 30278251
TI  - Striatal Signaling Regulated by the H3R Histamine Receptor in a Mouse Model of
      tic Pathophysiology.
AB  - Histamine dysregulation has been identified as a rare genetic cause of tic
      disorders; mice with a knockout of the histidine decarboxylase (Hdc) gene
      represent a promising model of this pathophysiology. How alterations in the
      histamine system lead to neuropsychiatric disease, however, remains unclear. The
      H3R histamine receptor is elevated in the striatum of Hdc KO mice, and H3R
      agonists, acting in the dorsal striatum, trigger tic-like movements in the model.
      In wild-type mice, H3R in the dorsal striatum differentially regulates mitogen
      activated protein kinase (MAPK) and protein kinase B (Akt) signaling in D1R
      dopamine receptor-expressing striatonigral medium spiny neurons (dMSNs) and D2R
      dopamine receptor-expressing striatopallidal MSNs (iMSNs), respectively. We
      examined the effects of H3R agonist treatment on MSN signaling in the Hdc-KO
      model. In dMSNs, MAPK signaling was elevated at baseline in the Hdc-KO model,
      resembling what is seen after H3R activation in WT animals. Similarly, in iMSNs,
      Akt phosphorylation was reduced at baseline in the KO model, resembling what is
      seen after H3R activation in WT animals. H3R activation in Hdc-KO mice further
      enhanced the baseline effect on Akt phosphorylation in iMSNs but attenuated the
      abnormality in MAPK signaling in dMSNs. These observations support the hypothesis
      that constitutive activity of upregulated H3R receptors in the Hdc-KO model
      mediates the observed alterations in baseline MSN signaling; but further
      activation of H3R, which produces tic-like repetitive movements in the model, has
      more complex effects.

PMID- 30278253
TI  - Frogs and tuns and tritons - A molecular phylogeny and revised family
      classification of the predatory gastropod superfamily Tonnoidea
      (Caenogastropoda).
AB  - The Tonnoidea is a moderately diverse group of large, predatory gastropods with
      ~360 valid species. Known for their ability to secrete sulfuric acid, they use it
      to prey on a diversity of invertebrates, primarily echinoderms. Tonnoideans
      currently are classified in seven accepted families: the comparatively well
      known, shallow water Bursidae, Cassidae, Personidae, Ranellidae, and Tonnidae,
      and the lesser-known, deep water Laubierinidae and Pisanianuridae. We assembled a
      mitochondrial and nuclear gene (COI, 16S, 12S, 28S) dataset for ~80 species and
      38 genera currently recognized as valid. Bayesian analysis of the concatenated
      dataset recovered a monophyletic Tonnoidea, with Ficus as its sister group.
      Unexpectedly, Thalassocyon, currently classified in the Ficidae, was nested
      within the ingroup as the sister group to Distorsionella. Among currently
      recognized families, Tonnidae, Cassidae, Bursidae and Personidae were supported
      as monophyletic but the Ranellidae and Ranellinae were not, with Cymatiinae,
      Ranella and Charonia supported as three unrelated clades. The Laubierinidae and
      Pisanianuridae together form a monophyletic group. Although not all currently
      accepted genera have been included in the analysis, the new phylogeny is
      sufficiently robust and stable to the inclusion/exclusion of nonconserved regions
      to establish a revised family-level classification with nine families: Bursidae,
      Cassidae, Charoniidae, Cymatiidae, Laubierinidae, Personidae, Ranellidae,
      Thalassocyonidae and Tonnidae. The results reveal that many genera as presently
      circumscribed are para- or polyphyletic and, in some cases support the rescue of
      several genus-group names from synonymy (Austrosassia, Austrotriton,
      Laminilabrum, Lampadopsis, Personella, Proxicharonia, Tritonoranella) or
      conversely, support their synonymization (Biplex with Gyrineum). Several species
      complexes are also revealed that merit further investigation (e.g., Personidae:
      Distorsio decipiens, D. reticularis; Bursidae: Bursa tuberosissima; Cassidae:
      Echinophoria wyvillei, Galeodea bituminata, and Semicassis bisulcata).
      Consequently, despite their teleplanic larvae, the apparently circumglobal
      distribution of some tonnoidean species is the result of excessive synonymy. The
      superfamily is estimated to have diverged during the early Jurassic (~186 Ma),
      with most families originating during a narrow ~20 My window in Albian-Aptian
      times as part of the Mesozoic Marine Revolution.

PMID- 30278252
TI  - Molecular phylogeny of Chondrocyclus (Gastropoda: Cyclophoridae), a widespread
      genus of sedentary, restricted-range snails.
AB  - The genus Chondrocyclus Ancey, 1898 contains the majority of southern African
      members of the Cyclophoridae, a large family of operculate land snails. We
      present the first molecular phylogeny of the genus based on two mitochondrial
      genes (16S and CO1) and complement this with an appraisal of morphological
      characters relating to the shell and soft parts. Worn shells on which some
      descriptions and records of different species were based appear to be
      indistinguishable morphologically, creating taxonomic confusion. We show that
      Chondrocyclus s.l. underwent two major radiations, one Afromontane and the other
      largely coastal. Accordingly, we recommend a revision recognising two genera.
      Chondrocyclus s.s. contains four monophyletic lineages, each characterized by a
      combination of morphological features. The Afromontane group is shown to be a
      species complex; relationships within this complex could not be resolved due to
      insufficient DNA sequence data. The molecular data confirms the monophyly of
      seven currently recognised species and provides evidence for at least twelve
      undescribed species; the morphological data are broadly consistent with this
      finding. The morphological data suggest that the two species from countries to
      the north of South Africa should be removed from the genus, and that
      Chondrocyclus sensu lato is endemic to South Africa. The historical biogeography
      of this group of microhabitat specialists with poor dispersal abilities
      contributes an additional, phylogenetically independent taxon to our
      understanding of the processes generating biodiversity in southern Africa, a
      natural laboratory for palaeobiogeography. All taxa are narrow-range endemics,
      underlining the importance of conserving South Africa's threatened forest
      habitats.

PMID- 30278254
TI  - Unravelling relationships among the shared stripes of sailors: Mitogenomic
      phylogeny of Limenitidini butterflies (Lepidoptera, Nymphalidae, Limenitidinae),
      focusing on the genera Athyma and Limenitis.
AB  - The phylogenetic relationships of the nymphalid butterfly tribe Limenitidini are
      best known for the genera Limenitis and Adelpha, model taxa for evolutionary
      processes such as Batesian mimicry and rapid adaptive radiations. Whereas these
      American limenitidines have received the most attention, phylogenetic
      relationships of their Asian relatives are still controversial and largely
      unexplored. Even one of the largest genera in Asia, Athyma, is polyphyletic. To
      clarify the phylogenetic relationships of these Asian Limenitidini, a total of 53
      representatives were sampled; 37 have their mitogenomes sequenced for the first
      time. Our phylogenetic results confirm that mitogenomic data provides well
      resolved relationships at most major levels of the phylogeny, even using
      different partition schemes or different inference methods. Interestingly, our
      results show that some Athyma taxa are embedded within the genus Limenitis,
      whereas the genus Tacola, previously considered to be a synonym of Athyma, needs
      to be recognized as a valid clade. Additionally, the other Limenitidini genera in
      Asia (namely Tarattia, Litinga, Sumalia, Pandita and Patsuia) are now grouped
      either within Athyma or Limenitis, so these genera need to be sunk. Importantly,
      we also show that the mainly Old World Limenitis and entirely New World Adelpha
      are sister groups, confirming the relevance of Asian lineages to global studies
      of Limenitis evolution.

PMID- 30278255
TI  - AgCa-PLGA submicron particles inhibit the growth and colonization of E. Faecalis
      and P. Gingivalis on dentin through infiltration into dentinal tubules.
AB  - Eliminating the infection from root canals and periodontal tissues of human teeth
      as well as the repair of infected periodontal bone has been a great challenge.
      Poly(lactide-co-glycolide) (PLGA) particles have been used for drug delivery due
      to their biodegradability, sustained drug release and nontoxic properties. As
      silver ions (Ag+) exhibit strong antibacterial ability and calcium ions (Ca2+)
      are essential for hard tissue regeneration, the Ag+ and Ca2+ were encapsulated
      into the PLGA particles to form AgCa-PLGA submicron particles. The physico
      chemical properties, ion release, cytotoxicity, ability to infiltrate dentinal
      tubules, antibacterial effects against Enterococcus faecalis (E. faecalis) and
      Porphyromonas gingivalis (P. gingivalis) in either planktonic or biofilm forms on
      dentin as well as in vitro mineralization ability were investigated. Results
      showed that Ag+ and Ca2+ were encapsulated into the AgCa-PLGA particles, which
      could release both Ag+ and Ca2+ over 30 days and exhibited strong antibacterial
      effects against E. faecalis and P. gingivalis. AgCa-PLGA particles could
      infiltrate into dentinal tubules by ultrasonic activation and inhibit the
      colonization of E. faecalis and P. gingivalis on dentin. AgCa-PLGA particles
      showed no cytotoxicity and induced hydroxyapatite (HA)-like crystal formation.
      AgCa-PLGA submicron particles could become a biomaterial for both infection
      control and hard tissue regeneration in dentistry and other related medical
      areas.

PMID- 30278256
TI  - Influence of preparation technique on co-amorphization of carvedilol with acidic
      amino acids.
AB  - Basic amino acids (AAs) have successfully been used as co-formers with acidic
      drugs for the preparation of co-amorphous formulations using ball-milling (BM)
      and spray-drying (SD). In contrast, acidic AAs have been reported as poor co
      formers for co-amorphous formulations, even for basic drugs, when using BM as a
      preparation technique. In this study the basic drug carvedilol (CAR) and the two
      acidic AAs, glutamic acid and aspartic acid, were used to explore the
      possibilities of producing co-amorphous formulations using BM, SD and liquid
      assisted grinding (LAG). X-ray powder diffraction, thermal analysis and Fourier
      transform infrared spectroscopy were used to determine the solid state form of
      the various CAR-AA mixtures prepared. BM the CAR-AA mixtures for 60 min did not
      result in co-amorphization as XRPD revealed remaining crystallinity of both CAR
      and the AA. On the other hand, successful co-amorphous salt formation was
      obtained for all SD samples. Differential scanning calorimetry showed that all
      the SD CAR-AA mixtures had a single glass transition temperature of approximately
      80  degrees C. The CAR-AA mixtures prepared by LAG showed some polymorphic
      conversion of CAR. Intrinsic dissolution testing showed the highest dissolution
      rate for all SD mixtures due to co-amorphous salt formation. Hence it was
      observed that of the three preparation techniques used, successful co-amorphous
      formulations of a basic drug with an acidic AA could only be prepared by SD.

PMID- 30278257
TI  - Enhanced dissolution of naproxen from pure-drug, crystalline nanoparticles: A
      case study formulated into spray-dried granules and compressed tablets.
AB  - This is a case study of the use of rapidly-dissolving naproxen crystalline
      nanoparticles to prepare compressed tablets. The dissolution rates of different
      formulations were determined: the crystalline pure-drug nanodispersion, a pure
      drug microsuspension, a granule prepared by spray drying the nanodispersion with
      mannitol, and a tablet prepared by compressing the granule with a bulking agent
      and a disintegrant. The goal was to determine the influence of each of the
      process steps on the rapid dissolution of the nanodispersion. A procedure was
      developed to allow sampling during the first 120 s of dissolution. Dissolution of
      the nanodispersion was completed after 60 s under both sink and non-sink
      conditions. Spray drying with mannitol delayed dissolution slightly under both
      sink and non-sink conditions. Under sink conditions a microsuspension (volume
      median size 11 um) showed similar rapid dissolution to the nanodispersion. We
      propose this to be a result of rapid shrinkage of the microparticles on
      dissolution under sink conditions. This nullifies any effects of specific surface
      on dissolution rate. Under non-sink conditions the microparticles retain their
      lower specific surface for a longer time during dissolution and dissolve
      therefore more slowly. When compressed into tablets, the dissolution rates of
      nanoparticles or microparticles were determined primarily by the tablet
      disintegration time; the influence of sink or non-sink conditions was only
      observable after disintegration.

PMID- 30278258
TI  - MiR-31 and miR-143 affect steroid hormone synthesis and inhibit cell apoptosis in
      bovine granulosa cells through FSHR.
AB  - The regulatory role of microRNAs (miRNAs) has been explored in ovarian cells, and
      the effects of miRNAs on gonadal development, apoptosis, ovulation, and steroid
      production have been reported. In this study, we analyzed the effects of follicle
      stimulating hormone (FSH) on miR-31 and miR-143 expression levels in bovine
      granulosa cells (GCs). Our results demonstrated that the FSH receptor (FSHR) is a
      common target gene of miR-31 and miR-143 in bovine GCs. We further analyzed the
      roles of miR-31 and miR-143 in bovine GCs by transfecting miR-31 and miR-143
      mimics and inhibitors. The Western blot and RT-PCR results showed that miR-31 and
      miR-143 reduced the mRNA and protein expression levels of FSHR. Moreover, miR-31
      overexpression decreased the secretion of progesterone (P4), and miR-143
      overexpression decreased both the synthesis of P4 and the secretion of estrogen
      (E2). In contrast, miR-31 inhibition increased the secretion of progesterone
      (P4), and miR-143 inhibition increased both the synthesis of P4 and the secretion
      of E2. Finally, we analyzed the possible effects of miR-31 and miR-143 on bovine
      GC apoptosis. The results showed that transfection with miR-31 and miR-143 mimics
      promoted GC apoptosis and that miR-143 and miR-31 inhibition reduced the rate of
      apoptosis in bovine GCs. Taken together, our results indicate that miR-31 and miR
      143 decrease steroid hormone synthesis and inhibit bovine GC apoptosis by
      targeting FSHR.

PMID- 30278259
TI  - Effect of equine chorionic gonadotropin administration on day 8 post-partum on
      ovarian follicular development, uterine health and uterine involution in
      lactating dairy cows.
AB  - The objective was to evaluate the effect of equine chorionic gonadotropin (eCG)
      injection on day 8 postpartum on ovarian cyclicity, uterine health and uterine
      involution in lactating dairy cows. Lactating dairy cows [n = 34, (21 primiparous
      and 13 multiparous)] were enrolled in the study. Animals were stratified by
      calving date, parity and BCS, and randomly assigned to either control (CON n =
      18) or eCG treatments (n = 16). On day 8 +/- 0.9 post-partum (pp), eCG treatment
      cows received a 2 ml i.m. injection (500 IU) of eCG and control treatment cows
      received a 2 ml i.m. injection of 0.9% sodium chloride. Ovaries were examined by
      transrectal ultrasound every second day from day 10 pp until ovulation or
      regression of the first follicle wave, and the diameter of the dominant follicle
      was recorded at each exam. Ultrasound exams were conducted on days 21, 28, 35 and
      42 pp to measure the diameter of the cervix and the uterine horns. Vaginal
      discharge score (VDS) was recorded on a 1 to 5 scale on days 14, 21, 28, 35 and
      42 pp. Endometrial cytology samples were collected on day 42 pp, and the
      percentage of polymorphonuclear neutrophils (PMN) determined. Milk samples were
      collected three times per week from day 14 pp until day 60 pp for P4
      determination. Ovarian follicular development variables, ovarian function
      variables analysed and incidence of subclinical endometritis were not affected by
      treatment. There was a treatment by parity interaction for pp interval to
      commencement of luteal activity (P = 0.04) and number of luteal phases (P =
      0.05), whereby eCG treatment caused an earlier pp commencement of luteal activity
      and a greater number of luteal phases in multiparous cows, but not in primiparous
      cows. A significant effect of treatment on uterine involution was observed
      (previously gravid horn: P = 0.03; previously non-gravid horn: P = 0.01) and
      uterine health status (P = 0.03), whereby eCG cows had smaller mean horn uterine
      diameter and lesser VDS than CON cows. In summary, parenteral administration of
      500 IU eCG on day 8 post-partum did not affect resumption of ovarian cyclicity in
      all cows but did enhance uterine involution and VDS. In multiparous cows, eCG
      advanced commencement of luteal activity and increased the number of luteal
      phases.

PMID- 30278261
TI  - Survival of Patients and Treatment-Related Outcome After Intra-Arterial
      Thrombolysis for Acute Lower Limb Ischemia.
AB  - BACKGROUND: The aim of this study is to evaluate the long-term survival and
      treatment-related outcome in patients treated with intra-arterial thrombolysis
      for acute lower limb ischemia. METHODS: The study was based on a prospective
      vascular database with retrospectively obtained supplementary information from
      the patients' files. Additionally, data on the patients' date and cause of death
      were obtained from Statistics Finland. A total of 155 patients with symptoms or
      signs of category I-IIa acute lower limb ischemia and angiographic evidence of
      native artery or bypass graft thromboembolic events were treated with intra
      arterial catheter-directed thrombolysis (CDT). Patients with severe ischemic
      stages at admission or those with contraindications for thrombolysis (n = 185)
      were treated with conventional surgical modalities and excluded from further
      analysis. RESULTS: The mean age of the patients at admission was 73 years (95%
      confidence interval 70.1-74.6). For descriptive purposes, age quartiles were used
      (<=64, 65-74, 75-82.5, >=83). The mean follow-up time was 126.3 months. The
      primary patency rates of native arteries/bypass grafts were 59.8%/31.7%,
      35.4%/17.1%, and 18.7%/15.2% at 1, 5, and 10 years, respectively (P = 0.01).
      Correspondingly, the respective secondary patency rates were 65.2%/55.6%,
      46.7%/39.8%, and 22.8%/30.5% (P = 0.88). A total of 190 additional procedures on
      122 patients were required to preserve the patency after hospital discharge. At 1
      year the cumulative survival was 78%, at 5 years 56%, and at 10 years 29%. The
      most common cause of death was cardiovascular (68.5%), predominantly presented by
      an acute coronary syndrome, while 9.6% died of cancer, 6.8% of pulmonary
      diseases, 8.2% of cerebrovascular causes, and 19.2% owing to trauma and other
      reasons. Atrial fibrillation (hazards ratio [HR] 2.31) and age over 83 years (HR
      5.23 per age category) were significantly and independently associated with
      poorer cumulative post-procedural survival. Bypass graft thrombosis was
      associated with an increase in major amputations after CDT (HR 14.77). However,
      the presence of synthetic bypass grafts had a protective influence on limb
      salvage (HR 0.086). A total of 39 (25.2%) major amputations were performed during
      the follow-up period. Age over 75 years was the only significant and independent
      factor to negatively impact on amputation-free survival (HR 2.01), which was 24%
      at 10 years. CONCLUSIONS: The long-term patency after CDT is unfavorable, and
      additional procedures are needed to preserve adequate distal perfusion.
      Approximately 30% of the patients are alive at 10 years after the initial CDT.
      Increasing age and atrial fibrillation have a negative effect on the patients'
      survival.

PMID- 30278260
TI  - Impact of an Educational Intervention on Ankle-Brachial Index Performance Among
      Medical Students and Fidelity Assessment at Six Months.
AB  - BACKGROUND: The resting ankle-brachial index (ABI) is a clinical test to diagnose
      peripheral artery disease. The Wyatt's score has been proposed to assess the
      students' performance on ABI measurement on a healthy volunteer (HV). No study
      has shown that this score is sensitive to different teaching methods. In this
      randomized controlled trial, we wanted to determine whether didactic learning
      alone or didactic learning combined with experiential learning improves
      proficiency in the ABI procedure assessed by the Wyatt's score. METHODS: Medical
      students (n = 30) received a didactic learning, including (1) a presentation of
      the ABI guidelines and (2) a video demonstration. Each student was then
      randomized into 2 groups ("the no experiential learning group" and "the
      experiential learning group"). An initial evaluation was performed after the
      didactic learning and then the final evaluation at the end of the intervention. A
      student was considered to be proficient when he performed a correct ABI procedure
      on an HV. The correct procedure corresponds to the following: (1) correctly
      answered Wyatt's score and (2) a difference in the ABI measurement between a
      professor in vascular medicine and a student was <=0.15. RESULTS: No student was
      proficient at the initial evaluation. At the final evaluation, there was a
      significant difference between the number of proficient students for the Wyatt's
      score depending on their learning group [didactic alone (1/10) or didactic +
      experiential training (15/20)] and also for the ABI procedure [didactic alone
      (0/10) or didactic + experiential training (16/20)]. At 6 months, among the 12
      students who passed the final evaluation, 4 students passed both the Wyatt's
      score and the ABI measurement. CONCLUSIONS: Our study demonstrates that the
      Wyatt's score was sensitive to an educational intervention and no improvement was
      found in the case of "no experiential learning." The Wyatt's score could be used
      to evaluate the student on ABI measurement after an educational intervention.
      TRIAL REGISTRATION: A randomized controlled trial was conducted in the Vascular
      Medicine Department of Rennes University Hospital (France). This was approved by
      the ethics review board of our institution (no. 16.150).

PMID- 30278262
TI  - Catheter-Directed Thrombolysis for Acute Limb Ischemia in an Asian Population.
AB  - BACKGROUND: The incidence of peripheral arterial occlusions in Asian populations
      is likely to increase exponentially in the present and future decades due to the
      adapted Western lifestyle in metropolitan Asian life, extended life expectancies,
      and high rates of smoking. The literature on thrombolytic treatment of peripheral
      arterial occlusions in Asian populations is limited. Therefore, we evaluated the
      thrombolysis results in a real-world contemporary Asian cohort of patients with
      peripheral arterial occlusions. METHODS: Retrospective review of all electronic
      patient records of patients who underwent thrombolytic therapy for peripheral
      arterial occlusions between July 2011 and July 2016 was conducted. Outcomes were
      angiographic patency, clinical success, bleeding complications, amputation rates,
      and mortality rates. RESULTS: In total, 82 patients (median age 66 years, range
      34-95) underwent catheter-directed thrombolysis. Median treatment duration was 26
      hr (3-209). Angiographic patency and clinical success rates were 64% and 66%,
      respectively. Bleeding complications occurred in 12% of patients of which 6% were
      major. Amputation-free rates were 81%, 67%, and 63% for 30 days, 6 months, and 1
      year, respectively. In-hospital mortality was 6%. CONCLUSIONS: This study
      demonstrates that thrombolytic treatment of peripheral arterial occlusions in an
      Asian patient cohort yields comparable treatment success rates to Western
      cohorts; however, higher rates of bleeding complications are hazardous and remain
      a detrimental drawback of this treatment.

PMID- 30278263
TI  - Remote Ischemic Pre-conditioning in the Management of Intermittent Claudication:
      A Pilot Randomized Controlled Trial.
AB  - BACKGROUND: Animal data suggest that remote ischemic conditioning (RIC) can
      improve blood flow in ischemic limbs and, consequently, may benefit claudication
      patients. Supervised exercise is the preferred first-line intervention for
      patients with intermittent claudication (IC) but is constrained by limited
      availability and logistical issues, particularly in rural settings. The aim of
      this study is to evaluate remote ischemic pre-conditioning in the management of
      intermittent claudication patients. METHODS: We undertook a randomized clinical
      trial to evaluate RIC's effect in claudication patients. Stable IC patients were
      randomly allocated to receive RIC alone, structured exercise (SE) alone, RIC plus
      SE, or to a control group which received standard advice and risk factor
      modification. Patients received their intervention over a 28-day period. RIC
      patients attended an RIC clinic every 3-4 days to undergo 4 cycles of 5-min upper
      limb ischemia followed by 5-min reperfusion induced with a standard blood
      pressure cuff. RESULTS: Forty-five patients were randomized, of whom 40 completed
      the trial (10 patients per group). The RIC alone, SE alone, and RIC plus SE
      groups all demonstrated significant improvements in pain-free walking distance
      and ankle-brachial pressure indices at 30 days. There were no differences in the
      magnitude of improvements between the groups. CONCLUSIONS: Compared with standard
      care RIC is promising as a home-delivered intervention. It appears to be
      equivalent to SE in the treatment of IC, with no apparent additive benefit to
      combining the 2 interventions in this small size sample. Large-scale randomized
      controlled trial is needed for validation.

PMID- 30278264
TI  - The Relationship between the Concentration of Cathepsin A, D, and E and the
      Concentration of Copper and Zinc, and the Size of the Aneurysmal Enlargement in
      the Wall of the Abdominal Aortic Aneurysm.
AB  - BACKGROUND: Despite advances in diagnostics and treatment, aortic aneurysms are
      an important clinical problem, mainly due to the accompanying complications that
      may lead to direct loss of life, also the number of diagnosed and operated
      aneurysms is constantly increasing. The aim of this study is to determine the
      relationship between the concentration of lysosomal peptidases cathepsin A, D,
      and E in the wall of the abdominal aortic aneurysm and the concentration of
      copper and zinc, and the size of the aneurysm widening in the wall of the
      abdominal aortic aneurysm. METHODS: The study included 27 patients with abdominal
      aortic aneurysm from the Department of Vascular Surgery and Transplantation of
      the University Clinical Hospital in Bialystok. The research material was the wall
      of the abdominal aortic aneurysm collected intraoperatively. The control material
      consisted of fragments of the abdominal aorta obtained from organ donors for
      transplantation. The concentration of cathepsin A, D, and E was determined using
      enzyme-linked immunosorbent assays. Concentrations of copper and zinc were
      determined by flame atomic absorption spectrometry after prior mineralization of
      the samples. All patients were interviewed and asked about basic demographic
      data, comorbidities, and risk factors for cardiovascular disease to which they
      were exposed in the past. The statistical analysis was performed using Statistica
      10 statistical package. Mann-Whitney U-tests were used and also Spearman's r
      correlation assuming a significance level of P < 0.05. RESULTS: The concentration
      of cathepsin A, D, and E was higher in the aortic wall altered by the aneurysm
      than in the wall of the control aorta (P < 0.05). The analysis of the data showed
      that there was a positive correlation between the concentration of cathepsin A
      and D and the width of the aneurysmal widening (r = 0.699 and 0.750,
      respectively). There was no correlation between cathepsin E concentration and
      aneurysm width. CONCLUSIONS: The higher contents of cathepsin A, D, and E in the
      wall of the aortic aneurysm than in the normal aortic wall, as well as a positive
      correlation between the concentration of cathepsin A and D and the width of the
      aneurysmal widening, allow to assume the participation of these enzymes in the
      pathogenesis of the aneurysm.

PMID- 30278265
TI  - Short Cuts in Surgical Ablation.

PMID- 30278266
TI  - Perioperative Statins for Ascending Aortic Repairs: Helpful or Hurtful?

PMID- 30278267
TI  - Bundled Payments for Surgical Care-More Questions Than Answers.
AB  - Bundled payment models assign financial responsibility for extended episodes of
      care up to 90 days after operation. The report by Koeckert et al, in this issue,
      describes 376 patients having either transcatheter aortic valve replacements or
      surgical aortic valve replacements. They investigated the impact of readmissions
      on the Bundled Payments for Care Improvement initiative (BPCI) payment for
      Medicare valve patients. The authors' hospital was designated as a BPCI
      institution that linked reimbursement to the different phases of care (in
      patient, outpatient follow-up, emergency visits, and other postacute care) up to
      90 days after operation. They found that bundled costs were significantly
      increased above BPCI reimbursements in readmitted patients, especially
      transcatheter aortic valve replacements patients who were readmitted late up to
      90 days after operation. This apparent disconnect between BPCI reimbursement and
      actual costs raises questions about BPCI reimbursement.

PMID- 30278268
TI  - Differential Effects of Normoxic and Hyperoxic Reperfusion on Global Myocardial
      Ischemia-Reperfusion Injury.
AB  - The objectives were to investigate if after hypoxia or ischemia, normoxic
      reperfusion is associated with less oxidant stress (OS), inflammation, and
      myocardial injury than hyperoxic reperfusion. In this study, cardiomyocytes (H9c2
      cells) were cultured in hypoxia, followed by reoxygenation in normoxia or
      hyperoxia. Cardiomyocyte OS, inflammation, and apoptosis were measured. In
      parallel experiments, rabbits were cannulated for cardiopulmonary bypass (CPB).
      Following cardioplegic arrest and aortic cross-clamp removal, hearts were
      reperfused under normoxic or hyperoxic conditions. Left ventricular developed
      pressure and contractility (LV +dP/dt) were recorded, and blood samples and heart
      tissues were collected for measurement of OS, inflammation, and cardiac injury.
      Results showed that H9c2 cells exposed to hyperoxic reoxygenation showed
      significant increases in OS, inflammation, and apoptosis compared to normoxic
      reoxygenation. Following CPB and 2-hour hyperoxic reperfusion, LV +dP/dt and left
      ventricular developed pressure were significantly decreased compared with pre-CPB
      values (to 36 +/- 21%, P = 0.002; and 53 +/- 20%, P = 0.02, respectively),
      associated with significant increases in all plasma and tissue biomarkers for OS,
      inflammation, and myocardial injury. In contrast, LV +dP/dt was relatively well
      preserved under normoxic reperfusion conditions (to 70 +/- 14% after 2-hour
      reperfusion), and was associated with an attenuated myocardial OS, inflammatory,
      apoptotic, and injury response compared to the hyperoxia group (eg, cTn-I: 5.9 +/
      1.5 vs 20.2 +/- 7.6 ng/mL, respectively, P < 0.0001). Overall, in both in vitro
      and in vivo experiments, normoxic reperfusion/reoxygenation was associated with
      less robust OS, inflammation, apoptosis, and myocardial injury compared with
      hyperoxic reperfusion/reoxygenation. These results suggest that hyperoxia should
      be avoided to minimize myocardial OS, inflammation, and ventricular dysfunction
      after CPB.

PMID- 30278269
TI  - Simultaneous Systemic to Pulmonary Shunt and Pulmonary Artery Banding is a Viable
      Option for Neonatal Palliation of Single Ventricle Physiology.
AB  - BACKGROUND: A subset of neonates with single ventricle (SV) physiology has
      antegrade pulmonary blood flow that is deemed unlikely to be reliable until
      Glenn. We have used systemic to pulmonary shunt (SPS) with pulmonary artery
      banding (PAB) to optimize pulmonary blood flow while maintaining reserve
      antegrade flow. We hypothesize that this is an effective strategy that can be
      accomplished without the routine need for cardiopulmonary bypass (CPB). METHODS:
      We retrospectively reviewed the records of 60 neonates who underwent combined
      SPS+PAB between 2004-2015. Data is presented as median with quartiles. RESULTS:
      Children were 8 (4-19) days old at surgery and included 38 (63%) boys. Atresia or
      severe stenosis of the sub-pulmonary atrioventricular (AV) valve associated with
      pulmonary blood flow across a bulbo-ventricular foramen (BVF) was present in
      37(62%). In 20 (33%), heterotaxy-associated unbalanced AV canal with pulmonary
      stenosis with or without anomalous pulmonary venous drainage was present. First
      stage palliation was accomplished without CPB in 44 patients (73%). There were
      seven (12%) hospital deaths, four amongst the 20 (20%) with heterotaxy. 53
      children were followed for a median 5.1 (1.8 - 8.2) years. Three early re
      interventions were required after initial palliation (one PAB adjustment, two SPS
      balloon angioplasties). Five additional heterotaxy patients experienced late
      mortality during follow-up. There were no early or emergent Glenn. 39 patients
      have reached Fontan circulation with a median pre-Fontan PA pressure of 14 (12
      18) mmHg. One patient converted to bi-ventricular physiology and the remaining
      await completion Fontan. Heterotaxy was the only independent predictor of
      mortality (hazard ratio 10 (2.3-44, p<0.001)). CONCLUSION: In SV patients with
      unreliable antegrade PA flow, SPS+PAB is an effective first stage palliation. SV
      patients with heterotaxy are at increased risk for mortality.

PMID- 30278270
TI  - Stop Draggin' My Heart Around: Recidivism, Intravenous Drug Use, and
      Endocarditis.

PMID- 30278271
TI  - Novel Implementation of a Cerebral Protection System During Ascending Thoracic
      Endovascular Aortic Repair (TEVAR).

PMID- 30278272
TI  - Pulmonary Vein Stenosis: Outcomes in Children with Congenital Heart Disease and
      Prematurity.
AB  - OBJECTIVES: Pulmonary vein stenosis (PVS) is a rare condition that has been
      linked to prematurity and congenital heart disease (CHD). Despite these
      associations, treatment options are limited and outcomes are guarded. We
      investigated differences in PVS outcomes based on the presence of CHD and
      prematurity, and risk factors for mortality or lung transplantation in PVS.
      METHODS: Single center retrospective cohort study of patients diagnosed with PVS
      between January 2005 and May 2016, identified by ICD codes with chart validation.
      Cox proportional hazard models assessed risk factors for the composite outcome of
      mortality or lung transplantation. RESULTS: Ninety-three patients with PVS were
      identified: 65 (70%) had significant CHD, 32 (34%) were premature, and 14 (15%)
      were premature with CHD. Sixty-five (70%) underwent a PVS intervention and 42
      (46%) underwent >=2 interventions. Twenty-five (27%) subjects died or underwent
      lung transplant 5.8 months (Interquartile range (IQR) 1.1, 15.3) after diagnosis.
      There was no difference in age at diagnosis or mortality based on presence of CHD
      or prematurity. PVS diagnosis before age 6 months and greater than one pulmonary
      vein affected at diagnosis were associated with higher mortality (HR 3.4 (95% CI
      1.5, 7.5), p=0.003, and HR 2.1 per additional vein affected (95% CI 1.3, 3.4),
      p=0.004, respectively). CONCLUSIONS: Survival in children with PVS is poor,
      independent of underlying CHD or prematurity. Younger age and greater number of
      veins affected at diagnosis are risk factors for worse outcome. Understanding
      causal mechanisms and development of treatment strategies are necessary to
      improve outcomes.

PMID- 30278273
TI  - Dynamics of oxytetracycline, sulfamerazine, and ciprofloxacin and related
      antibiotic resistance genes during swine manure composting.
AB  - Understanding the dynamics of veterinary antibiotic and related antibiotic
      resistance genes (ARGs) during swine manure composting is crucial in assessing
      the environmental risk of antibiotics, which could effectively reduce their
      impact in natural environments. This study investigated the dissipation of
      oxytetracycline (OTC), sulfamerazine (SM1) and ciprofloxacin (CIP) as well as the
      behaviour of their corresponding ARGs during swine manure composting. These
      antibiotics were added at two concentration levels and two different methods of
      addition (single/mixture). The results indicated that the removal efficiency of
      antibiotics by composting were >=85%, except for the single-SM1 treatment. The
      tetracycline resistance genes (TRGs) encoding ribosomal protection proteins (RPP)
      and efflux pump (EFP) and fluoroquinolone resistance genes (FRGs) could be
      effectively removed after 42 days. On the contrary, the TRGs encoding enzymatic
      inactivation (EI) and sulfonamide resistance genes (SRGs) were enriched up to 31
      fold (sul 2 in single-low-SM1). Statistical analyses indicated that the behaviour
      of these class antibiotics and ARGs were controlled by microbial activity and
      significantly influenced by environmental factors (mainly C/N, moisture and pH)
      throughout the composting process.

PMID- 30278274
TI  - Sequencing batch biosorption of micropollutants from aqueous effluents by
      rapeseed waste: Experimental assessment and statistical modelling.
AB  - Rapeseed (RS) waste was used for sequential biosorption from aqueous solutions of
      two target micropollutants: lead ions and Reactive blue 19 (Rb19) dye, through an
      integrated approach, combining experimental assessment and statistical modeling.
      In both cases of sequential biosorption, a pseudo-second order kinetic model
      fitted the biosorption data well. Intraparticle diffusion proved to be the rate
      limiting step in the sequential retention of both micropollutants. A selective
      desorption of metal ions and anionic dye at pH 2.5 and 10.5, respectively was
      observed. The quadratic models generated by response surface methodology (RSM)
      adequately described the sequential biosorption process and the desorption
      process, respectively. XPS and FTIR analysis indicated the mechanisms involved in
      the retention of target pollutants.

PMID- 30278275
TI  - Comparing the effects of three in situ methods on nitrogen loss control,
      temperature dynamics and maturity during composting of agricultural wastes with a
      stage of temperatures over 70  degrees C.
AB  - The study investigated the effects of three in situ methods for controlling
      nitrogen loss and maturity with different mechanisms: struvite-based addition
      (K2HPO4 and MgO, MP), woody peat addition (WP) and intermittent aeration (IA),
      during composting of vegetable waste (cucumber vine) with temperature over 70 
      degrees C to inactivate potential viral pathogens. The experiment was conducted
      in a 200 L pilot-scale composting system, with which temperature and ammonia
      emission were recorded in real time, and solid samples were collected and
      analyzed during the process. The results indicated that the methods of MP and IA
      reduced the total nitrogen loss by 27.5% and 16.1%, respectively, without
      inhibitory effects on the temperature, nutrient availability and maturity. The WP
      method significantly decreased the nitrogen loss but could not maintain the
      thermophilic stage over 70  degrees C, because of its influence on the material
      physio-chemical characteristics caused by woody peat addition. In conclusion, all
      three methods could promote the maturity process, and 20 days should be adequate
      for vegetable waste composting with a good nutrient availability. Considering the
      two factors of reducing nitrogen loss and achieving high temperatures together,
      we recommended the struvite-based controlling method with the mechanism of
      chemisorption to reduce nitrogen loss during vegetable waste composting that
      requires temperatures over 70  degrees C.

PMID- 30278276
TI  - Call for papers: Deep phenotyping for Precision Medicine.

PMID- 30278277
TI  - Exploring different photosensitizers to optimize elimination of planktonic and
      biofilm forms of Enterococcus faecalis from infected root canal during
      antimicrobial photodynamic therapy.
AB  - BACKGROUND: Despite the high success rate of endodontic treatment, failure may
      occur in some cases. In this case, Enterococcus faecalis is the most common
      species in endodontic treatment failure and post-treatment apical periodontitis.
      Therefore, a new adjunctive strategy is needed for the prevention of endodontic
      infections due to E. faecalis. The aim of the present study was to compare the
      antimicrobial and anti-biofilm activities of different common photosensitizers
      (PSs) for use in antimicrobial photodynamic therapy (aPDT) against E. faecalis.
      MATERIALS AND METHODS: E. faecalis strain ATCC 29212 was used as the tested
      strain and methylene blue (MB), toluidine blue O (TBO), indocyanine green (ICG),
      and curcumin (CUR) were used as PSs. Irradiation was carried out using diode
      laser and light emitting diode (LED) at wavelengths related to the above PSs.
      Then, antimicrobial and anti-biofilm activities were measured using the microbial
      viability assay and crystal violet test, respectively. RESULTS: aPDT with using
      the above PSs significantly decreased the CFU/mL count of E. faecalis compared to
      the control group (P < 0.05). The killing percentage of E. faecalis via PS
      mediated aPDT was 99.6%, 98.2%, 85.1%, and 65.0% for CUR, ICG, TBO, and MB,
      respectively. aPDT using the above PSs significantly decreased the biofilm
      formation ability of E. faecalis compared to the control group (P < 0.05). The
      biofilm reduction percentage of the PSs was 68.4%, 62.9%, 59.0%, and 47.6% for
      CUR, ICG, TBO, and MB, respectively. CONCLUSION: CUR and ICG mediated aPDT
      exhibited considerably more antimicrobial activity than other PSs, while TBO and
      MB demonstrated weaker anti-biofilm effects against E. faecalis compared to other
      PSs.

PMID- 30278278
TI  - Potassium iodide potentiated photodynamic inactivation of Enterococcus faecalis
      using Toluidine Blue: Comparative analysis and post-treatment biofilm formation
      study.
AB  - BACKGROUND: Photodynamic Inactivation (PDI) has recently gained interest as an
      alternative modality to fight pathogenic entities and its effect can be further
      enhanced by using certain inorganic salts. Here, the Potassium Iodide (KI)
      mediated PDI effect on Enterococcus faecalis using Toluidine Blue Ortho (TBO) as
      photosensitizer (PS) has been evaluated, and subsequent Biofilm formation extent
      is accounted for. METHODS: The comparative photoinactivation of TBO and TBO/KI on
      E.faecalis was investigated by quantifying surviving bacterial colonies after
      laser irradiation with 30,60, and 180 s exposure times and different
      PS/Potentiator concentrations. The biofilm formation capability of E.faecalis was
      observed by calculating Optical Density (OD595) of samples 24,48, and 72 h post
      PDI treatment. Scanning Electron Microscopy (SEM) was used as a qualitative
      measure of bacterial biofilm growth. RESULTS: More than 4 LOGS of photokilling
      was obtained for experimental groups with the highest PS/KI concentrations at 180
      s exposure time. All KI-potentiated groups showed enhancement in PDI effect when
      compared to non-potentiated counterparts. The degree of recurring biofilm for
      laser-treated groups also showed to be much less than that of control group, as
      confirmed by both OD595 measurement and SEM imaging.

PMID- 30278279
TI  - Porphyrins containing basic aliphatic amino groups as potential broad-spectrum
      antimicrobial agents.
AB  - New porphyrin derivatives bearing basic aliphatic amino groups were synthesized
      from the condensation of meso-4-[(3-N,N
      dimethylaminopropoxy)phenyl]dipyrromethane, pentafluorobenzaldehyde and 4-(3-N,N
      dimethylaminopropoxy)benzaldehyde. The reaction was catalyzed by trifluoroacetic
      acid in acetonitrile. This approach was used to obtain porphyrins with different
      patterns of substitution, of which three of them were isolated: 5,15-di(4
      pentafluorophenyl)-10,20-di[4-(3-N,N-dimethylaminopropoxy)phenyl]porphyrin
      (F10APP), 5-(4-pentafluorophenyl)-10,15,20-tris[4-(3-N,N
      dimethylaminopropoxy)phenyl]porphyrin (F5APP) and 5,10,15,20-tetrakis[4-(3-N,N
      dimethylaminopropoxy)phenyl]porphyrin (TAPP). The UV-vis spectroscopic
      characterizations and the photodynamic effect of these compounds were compared in
      N,N-dimethylformamide. These porphyrins showed red fluorescence emission with
      quantum yields of 0.09-0.15. Moreover, they sensitized the production of singlet
      molecular oxygen, reaching quantum yields values of 0.33-0.53. Photodynamic
      inactivation was studied in two bacteria, Staphylococcus aureus and Escherichia
      coli, and a yeast Candida albicans. High amount of cell-bound porphyrin was
      obtained at short times (<2 min) of incubation. After 15 min irradiation, a 7 log
      reduction of S. aureus was found for cells treated with 1 MUM F5APP. Similar
      photokilling was obtained in E. coli, but using 7.5 MUM F5APP and 30 min
      irradiation. Under these conditions, a decrease of 5 log was observed in C.
      albicans cells. An increase in cell survival was observed by addition of sodium
      azide, whereas a slight protective effect was found in the presence of D
      mannitol. Moreover, the photoinactivation mediated by these porphyrins was higher
      in D2O than in water. Thus, these porphyrins induced the photodynamic activity
      mainly through the intermediacy of O2(1Deltag). In particular, F5APP was a highly
      effective photosensitizer with application as a broad-spectrum antimicrobial.
      This porphyrin contains three basic aliphatic amino groups that may be protonated
      at physiological pH. In addition, it is substituted by a lipophilic
      pentafluorophenyl group, which confers an amphiphilic character to the
      tetrapyrrolic macrocycle. This effect can increase the interaction with the cell
      envelopment, improving the photocytotoxic activity against the microorganisms.

PMID- 30278280
TI  - Low-cost light-induced therapy to treat rickettsial infection.
AB  - Antimicrobial photodynamic therapy uses a nontoxic photosensitizer with the
      assistance of harmless visible light to activate the photosensitizer.
      Consequently, the excited state of the photosensitizer interacts with molecular
      oxygen to produce reactive oxygen species, which have the antimicrobial effect.
      In this study, we evaluated the effect of photodynamic therapy on Vero cells
      infected with rickettsia using methylene blue as a photosensitizer along with red
      light. A significant reduction (by 96%) in the number of viable Rickettsia
      slovaca was determined by quantitative RT-PCR 48 h after the treatment with
      methylene blue followed by 30 min of red light excitation. A statistically
      significant reduction of R. slovaca was also recorded with pretreatment (by 99%).
      To the best of our knowledge, this result is the first one in the literature to
      confirm the effectiveness of photodynamic therapy for the elimination of R.
      slovaca and to suggest this technique as a good supportive treatment for
      rickettsial infections.

PMID- 30278281
TI  - Design, synthesis and biological evaluation of N1-(isoquinolin-5-yl)-N2
      phenylpyrrolidine-1,2-dicarboxamide derivatives as potent TRPV1 antagonists.
AB  - Reported herein is the design, synthesis, and pharmacologic evaluation of a class
      of TRPV1 antagonists constructed on a N1-(isoquinolin-5-yl)-N2-phenylpyrrolidine
      1,2-dicarboxamide platform that evolved from a 5-aminoisoquinoline urea lead.
      Advancing the SAR of this series led to the eventual identification of 3b,
      comprising a p-Br substituted phenyl. In a TRPV1 functional assay, using cells
      expressing recombinant human TRPV1 channels, 3b displayed potent antagonism
      activated by capsaicin (IC50 = 0.084 MUM) and protons (IC50 = 0.313 MUM). In the
      preliminary analgesic and body temperature tests, 3b exhibited good efficacy in
      capsaicin-induced and heat-induced pain models and without hyperthermia side
      effect. On the basis of its superior profiles, 3b could be considered as the lead
      candidate for the further development of antinociceptive drugs.

PMID- 30278282
TI  - Design, synthesis, modeling studies and biological evaluation of thiazolidine
      derivatives containing pyrazole core as potential anti-diabetic PPAR-gamma
      agonists and anti-inflammatory COX-2 selective inhibitors.
AB  - Nowadays, diabetes and its associated inflammatory complications are important
      public health problems worldwide. Market limitations of drugs with dual actions
      as anti-inflammatory (AI) and anti-diabetic have been led to a temptation for
      focusing on the discovery and development of new compounds with potential AI and
      anti-diabetic activities. Herein, we synthesized two new series containing
      pyrazole ring with vicinal diaryl rings as selective COX-2 moiety and
      thiazolidindione (series 12a-f) or thiazolidinone (series 13a-f) as anti-diabetic
      moiety and the two moieties were linked together with methylene or
      methylenehydrazone functionality. The two series were evaluated for their COX
      inhibition, AI activity and ulcerogenic liability and for the anti-diabetic
      activity; 12a-f and 13a-f were assessed in vitro against alpha-glucosidase, beta-
      glucosidase, in vivo hypoglycemic activity (one day and 15 days studies) in
      addition to PPARgamma activation study. Four compounds (12c, 12f, 13b and 13f)
      had higher COX-2 S.I. (8.69-9.26) than the COX-2 selective drug celecoxib (COX-2
      S.I. = 8.60) and showed the highest AI activities and the lowest ulcerogenicity
      than other derivatives. Also, two thiazolidindione derivatives 12e and 12f and
      two thiazolidinone derivatives 13b and 13c showed higher inhibitory activities
      against alpha- and beta-glucosidase (% inhibitory activity = 62.15, 55.30, 65.37,
      59.08 for alpha-glucosidase and 57.42, 60.07, 58.19, 66.90 for beta-glucosidase
      respectively) than reference compounds (acarbose with % inhibitory activity =
      49.50 for alpha-glucosidase and d-saccharic acid 1,4-lactone monohydrate with %
      inhibitory activity = 53.42 for beta-glucosidase) and also showed good PPAR-gamma
      activation and good hypoglycemic effect in comparison to pioglitazone and
      rosiglitazone. Moreover, Shape comparison and docking studies were carried out to
      understand their interaction and similarity with standard drugs.

PMID- 30278283
TI  - RUNX1-EVI1 induces dysplastic hematopoiesis and acute leukemia of the
      megakaryocytic lineage in mice.
AB  - The RUNX1-EVI1 gene generated by the t(3;21) translocation encodes a chimeric
      transcription factor and is a causative gene in the development of de novo acute
      megakaryoblastic leukemia and leukemic transformation of hematopoietic stem cell
      tumors. Heterozygous RUNX1-EVI1 knock-in mice die in utero due to hemorrhage in
      the central nervous system and spinal cord and complete abolishment of definitive
      hematopoiesis in the fetal liver. On the other hand, the chimeric knock-in mouse
      develops acute megakaryoblastic leukemia. We created another mouse model of RUNX1
      EVI1 using transplantation of retrovirus-infected bone marrow cells. Some mice
      transplanted with RUNX1-EVI1-expressing bone marrow cells developed acute
      megakaryoblastic leukemia within eight months, and the other non-leukemic mice
      showed thrombocytosis at around a year. In the non-leukemic mice, dysplastic
      megakaryocytes proliferated in the bone marrow and frequently infiltrated into
      the spleen, which was not associated with marrow fibrosis. In the leukemic mice,
      their tumor cells were positive for c-kit and CD41, and negative for TER119.
      Although they were negative for platelet peroxidase in the electron microscopic
      analysis, they had multiple centrioles in the cytoplasm, which are characteristic
      of megakaryocytes that undergo endomitosis. The leukemic cells were serially
      transplantable, and gene-expression analyses using quantitative RT-PCR arrays
      revealed that they showed significantly elevated expression of stem cell,
      primitive hematopoietic cell and endothelial cell-related genes compared with
      normal bone marrow cells. All these data suggested that RUNX1-EVI1 caused
      dysplastic hematopoiesis or leukemia of the megakaryocytic lineage and endowed
      gene expression profiles distinctive of immature hematopoietic cells.

PMID- 30278286
TI  - Potential in vitro and ex vivo targeting of bZIP53 involved in stress response
      and seed maturation in Arabidopsis thaliana by five designed peptide inhibitors.
AB  - Basic leucine zipper (bZIP) transcription factors (TFs) are eukaryote-specific
      proteins that bind to DNA as a homodimer or heterodimer and regulate gene
      expression. They are involved in several biological processes in plants;
      therefore inhibiting bZIP-DNA binding activity by targeting protein-protein
      interface is an attractive proposition with aspects of both basic and applied
      biology. Here, we describe the equilibrium and kinetic interactions studies of a
      designed peptide inhibitor A-ZIP53 and its four variants with the bZIP53 protein,
      a key regulator of seed maturation phase and stress response in Arabidopsis. Five
      designed peptide inhibitors were primed to preferentially interact with bZIP53
      and inhibit its DNA binding activity. Isothermal circular dichroism (CD) studies
      were used to quantify the structural changes accompanying heterodimers formation
      between bZIP53 and five A-ZIP53s. Equilibrium studies using electrophoretic
      mobility shift assay (EMSA) and fluorescence polarization (FP) assays suggest
      that A-ZIP53s and bZIP53 mixture form heterodimers, incapable of binding to DNA.
      Four A-ZIP53 derivatives were designed with additional interactions that drive
      heterodimerization with bZIP53. A-ZIP53s dose-dependent FP studies show that
      peptide inhibitors displaced the DNA bound bZIP53 with nM half-maximal inhibitory
      (IC50) concentrations. Using FP, time-dependent displacement kinetic studies were
      used to rank five A-ZIP53s for their abilities to displace DNA-bound bZIP53 with
      a rank order of A-ZIP53 < A-ZIP53(A -> E) < A-ZIP53(N -> A) < A-ZIP53(R -> E) < A
      ZIP53(A -> E,N -> A). In transient transfection assays, bZIP53-mediated GUS
      activity was inhibited by equimolar concentrations of five A-ZIP53s with A
      ZIP53(A -> E,N -> A) the most effective one. Similar peptide inhibitors may be
      designed against other bZIP proteins to study their functions in vivo.

PMID- 30278285
TI  - Effectiveness of a school-based intervention to prevent child sexual abuse
      Evaluation of the German IGEL program.
AB  - BACKGROUND: Child sexual abuse (CSA) is a problem with severe consequences for
      victimized children. A variety of interventions have been developed and
      implemented over the last decades to prevent CSA. However, most of them have not
      been systematically evaluated to determine their effectiveness. The IGEL program
      is a school-based intervention to prevent CSA in third-grade primary school
      children in Germany. METHODS: This study was conducted using a quasi-experimental
      design, in which almost 300 children and their parents from eight intervention
      and four control schools were surveyed three times (pretest, posttest, 3 months
      later). In order to measure outcomes, a questionnaire was developed based on
      validated instruments to assess the knowledge, courses of action and self
      protective skills of the children. Furthermore, increased anxiety and generalized
      touch aversion were examined as potentially harmful side effects of the program.
      RESULTS: The results clearly demonstrate increased CSA-related knowledge and
      courses of action in children from the intervention group compared to the control
      children. These effects were medium-sized and sustained for at least three months
      after the last session. No meaningful negative side effects were detected in the
      evaluation for either the children or parents. CONCLUSION: The outcome evaluation
      indicates that the IGEL program is an effective intervention in terms of
      knowledge about CSA and known courses of action, and may therefore contribute to
      the prevention of CSA in primary schools. Despite this positive core finding of
      the intermediate outcomes, some adaptations of the program to children with
      different cultural backgrounds were made prior to further dissemination.

PMID- 30278287
TI  - Predicting the location of the non-local contacts in alpha-synuclein.
AB  - In this paper, the Sequential Collapse Model (SCM) for protein folding pathways
      is applied to investigate the location of the non-local contacts in the
      intrinsically disordered state of alpha-synuclein, a protein implicated in the
      onset and spreading of several serious neurodegenerative diseases. The model
      relies on the entropic cost of forming protein loops due to self-crowding
      effects, and the protein sequence to determine contact location and stability. It
      is found that the model predicts the existence of several possible non-local
      contacts, and the location of the non-local contacts is consistent with existing
      experimental evidence. The bearing of these findings on the pathogenic mechanism
      and its regulation is discussed.

PMID- 30278284
TI  - Mechanisms of persistence by small DNA tumor viruses.
AB  - Virus infection contributes to nearly 15% of human cancers worldwide. Many of the
      oncogenic viruses tend to cause cancer in immunosuppressed individuals, but
      maintain asymptomatic, persistent infection for decades in the general
      population. In this review, we discuss the tactics employed by two small DNA
      tumor viruses, Human papillomavirus (HPV) and Merkel cell polyomavirus (MCPyV),
      to establish persistent infection. We will also highlight recent key findings as
      well as outstanding questions regarding the mechanisms by which HPV and MCPyV
      evade host immune control to promote their survival. Since persistent infection
      enables virus-induced tumorigenesis, identifying the mechanisms by which small
      DNA tumor viruses achieve latent infection may inform new approaches for
      preventing and treating their respective human cancers.

PMID- 30278289
TI  - From pattern to process: studies at the interface of gene regulatory networks,
      morphogenesis, and evolution.
AB  - The development of anatomical structures is complex, beginning with patterning of
      gene expression by multiple gene regulatory networks (GRNs). These networks
      ultimately regulate the activity of effector molecules, which in turn alter
      cellular behavior during development. Together these processes biomechanically
      produce the three-dimensional shape that the anatomical structure adopts over
      time. However, the interfaces between these processes are often overlooked and
      also include counter-intuitive feedback mechanisms. In this review, we examine
      each step in this extraordinarily complex process and explore how evolutionary
      developmental biology model systems, such as butterfly scales, vertebrate teeth,
      and the Drosophila dorsal appendage offer a complementary approach to expose the
      multifactorial integration of genetics and morphogenesis from an alternative
      perspective.

PMID- 30278288
TI  - Structural characterization of 1-deoxy-D-xylulose 5-phosphate Reductoisomerase
      from Vibrio vulnificus.
AB  - Vibrio vulnificus, a gram-negative bacterium, is the leading cause of seafood
      borne illnesses and mortality in the United States. Previous studies have
      identified metabolites 2-C-methylerythritol 4-phosphate (MEP) as being essential
      for V. vulnificus growth and function. It was shown that 1-deoxy-D-xylulose-5
      phosphate reductoisomerase (Dxr) is a critical enzyme in the viability of V.
      vulnificus, and many other bacteria, as it catalyzes the rearrangement of 1-deoxy
      D-xylulose-5-phosphate (Dxp) to 2-C-methylerythritol 4-phosphate (MEP) within the
      MEP pathway, found in plants and bacteria. The MEP pathway produces the
      isoprenoids, isopentenyl diphosphate and dimethylallyl pyrophosphate. In this
      study, we produced and structurally characterized V. vulnificus Dxr. The enzyme
      forms a dimeric assembly and contains a metal ion in the active site. Protein
      produced in Escherichia coli co-purifies with Mg2+ ions, however the Mg2+ cations
      may be substituted with Mn2+, as both of these metals may be utilized by Dxrs.
      These findings will provide a basis for the design of Dxr inhibitors that may
      find application as antimicrobial compounds.

PMID- 30278290
TI  - A Practical Cadaveric Model for Intracranial Bypass Training.
AB  - BACKGROUND: Intracranial bypass is technically challenging and difficult to learn
      owing to its relative rarity and complexity. Although multiple training models
      for intracranial bypass exist, a detailed depiction of the use and fidelity of
      cadaveric specimens for bypass training is lacking in the literature. This study
      describes use of preserved cadaveric specimens as a practical training model for
      performance of multiple intracranial bypasses and discusses the surgical setup
      for a cadaveric bypass laboratory. METHODS: Using a cadaveric specimen and basic
      microneurosurgical instruments and supplies, 5 intracranial bypasses were
      performed (superficial temporal artery [STA]-to-middle cerebral artery [MCA], MCA
      to-MCA, STA-to-posterior cerebral artery [PCA], anterior cerebral artery-to
      anterior cerebral artery, and posterior inferior cerebellar artery-to-posterior
      inferior cerebellar artery) using pterional, subtemporal, interhemispheric, and
      suboccipital approach. Bypass integrity was assessed by direct fluid injection
      into the adjacent vessel segment. All procedures were recorded. RESULTS:
      Procedural steps mirrored actual bypass surgery and included vessel marking,
      performance of arteriotomy, and completion of an end-to-end, end-to-side, or side
      to-side anastomosis. Simulations included anatomically appropriate exposures of
      common intracranial (MCA, PCA, posterior inferior cerebellar artery, anterior
      cerebral artery) and extracranial (STA) vessels encountered during cerebral
      bypass surgery and high-fidelity recreations of the operative corridors
      associated with deeper anastomoses, such as STA-to-PCA bypass. Vessel diameters
      were 1.5-2.1 mm, and anastomosis times were 20-40 minutes. Immediate feedback on
      anastomotic integrity was achieved via direct fluid injection adjacent to the
      anastomosis site. CONCLUSIONS: The cadaveric specimen trainee model is a
      relatively simple yet high-fidelity approach for learning intracranial bypass.

PMID- 30278291
TI  - Risk factors of intra-procedural rupture in the endovascular treatment of
      unruptured intracranial aneurysms: a single center experience with 1232
      procedures.
AB  - BACKGROUND: and purpose: Intra-procedural rupture (IPR) is a rare complication
      during endovascular treatment (EVT) of unruptured intracranial aneurysms (UIAs),
      however, universally leads to poor outcomes if not properly managed. In this
      study, we intend to illuminate the risk factors of IPR during EVT of UIAs.
      METHODS: Patients with UIAs treated with EVT in our center from January 2010 to
      March 2017 were retrospectively collected and reviewed. Univariate analysis and
      multivariate logistic analysis were performed to analyze the risk factors of IPR.
      RESULTS: A total of 1232 patients with 1312 unruptured aneurysms were included in
      the study. IPR occurred in 11 patients (0.9%). Univariate analysis showed that
      cardiac comorbidities, irregular morphology and location on anterior
      communicating artery were significantly associated with IPR (P<0.05). In
      addition, stent placement was related to lower risk of IPR compared with non
      stent placement (P=0.024). The multivariate analysis showed that cardiac
      comorbidities (P=0.016, OR=6.320), irregular morphology (P=0.001, OR=9.562) and
      location on AcomA (anterior communicating artery) (P=0.006, OR=6.971) were
      independent risk factors of IPR. CONCLUSION: The occurrence rate of intra
      procedural rupture was relatively low. Cardiac comorbidities, irregular
      morphology and location on AcomA are independent risk factors of intra-procedural
      rupture. Stents and flow diverters are safe and feasible in treating UIA, with
      significantly low risk of intra-procedural rupture.

PMID- 30278292
TI  - Degenerative Lumbar Spondylolisthesis: Biochemical Aspects and Evaluation of
      Stabilization Surgery Extent in Terms of Adjacent Segment Disease Theory.
AB  - OBJECTIVE: In lumbar degenerative spondylolisthesis (DSL), the criteria and
      extent of surgical treatment have not been strictly defined owing to the adjacent
      segment disease theory and unclear molecular pathogenesis. The present study
      analyzed the clinical and radiographic findings of patients after lower lumbar
      fusion surgery with single and 2-level DSL and explored the inflammatory
      mediator's role in DSL evolution and symptoms. METHODS: The prospective follow-up
      of patients with DSL, stratified by the stabilization extent (L4-L5, L5-S1, and
      L4-S1), included the Back Illness Pain and Disability 9-item questionnaire and
      native and dynamic radiographs to evaluate the intervertebral disc height and
      adjacent segments' angular motion. Follow-up examinations were performed at 3,
      12, and 24 months. The pathological cytokine concentrations in the intervertebral
      disc and facet joints of the subchondral bone were assessed using the BioPlex
      assay in perioperatively collected patient samples and compared with those of
      control subjects obtained during multiorgan procurement. These findings were
      correlated with pain localization and severity. RESULTS: Statistical analysis of
      the questionnaire data revealed significant postoperative improvement in all
      patients, in particular, the L4-L5 group. Also, we found radiographic evidence of
      angular motion reduction in both adjacent segments near the limits of statistical
      significance and a meaningful correlation with subjective status improvement at
      24 months. BioPlex analysis revealed platelet-derived growth factor 2 B subunits,
      interleukin-6, interleukin-8, and tumor necrosis factor-alpha were elevated in
      spinal unit segments and the interleukin-1beta levels correlated significantly
      with the intensity of low backache. CONCLUSIONS: Our findings did not support the
      adjacent segment disease theory. However, later development of these changes
      could not be excluded. The cytokines, chemokines, and growth factors play a
      significant role in DSL pathogenesis and symptoms.

PMID- 30278293
TI  - Endoscope assisted Microvascular Decompression for the Management of Hemifacial
      Spasm caused by Vertebrobasilar dolichoectasia.

PMID- 30278294
TI  - Tolerability of adjunctive eslicarbazepine acetate according to concomitant
      lamotrigine or carbamazepine use: A subgroup analysis of three phase III trials
      in adults with focal (partial-onset) seizures.
AB  - OBJECTIVE: To evaluate and compare the effects of concomitant lamotrigine (LTG)
      or carbamazepine (CBZ) on the incidence of treatment-emergent adverse events
      (TEAEs) in patients taking adjunctive eslicarbazepine acetate (ESL) for focal
      (partial-onset) seizures (FS). METHODS: These post-hoc analyses of data pooled
      from three randomized, double-blind, placebo-controlled studies of adjunctive ESL
      (BIA-2093-301, -302 and -304) included adults (>=16 years) with FS refractory to
      1-3 antiepileptic drugs (AEDs). Patients were randomized equally to placebo, ESL
      400 mg (Studies 301 and 302 only), 800 mg, or 1200 mg once daily (8-week
      baseline, 2-week titration, and 12-week maintenance periods). TEAEs, TEAEs
      leading to discontinuation, and serious AEs (SAEs) were evaluated in patients
      taking, or not taking, LTG (excluding those taking CBZ or phenytoin [PHT]; i.e.,
      the +LTG and -LTG/-CBZ subgroups), or CBZ (excluding those taking LTG or PHT;
      i.e., the +CBZ and -LTG/-CBZ subgroups) at baseline. RESULTS: LTG was used
      concomitantly by 248 patients (+LTG; placebo, n = 81; ESL, n = 167) and CBZ by
      613 patients (+CBZ; placebo, n = 172; ESL, n = 441); 361 patients were taking
      neither LTG nor CBZ (-LTG/-CBZ; placebo, n = 109; ESL, n = 252). The overall
      incidence of TEAEs with ESL (any dose) was numerically higher for +CBZ (77%) than
      for +LTG (73%) or -LTG/-CBZ (68%; statistical significance not tested). Among
      patients taking ESL, dizziness, diplopia, and vomiting were reported more
      frequently in the +CBZ subgroup (30%, 14%, and 10%, respectively) than in the
      +LTG (16%, 8%, 5%) or -LTG/-CBZ (11%, 3%, 5%) subgroups. The overall incidence of
      TEAEs leading to discontinuation with ESL was higher for +CBZ (21%) than for +LTG
      (13%) or -LTG/-CBZ (15%). Dizziness leading to discontinuation with ESL was
      reported more frequently in the +CBZ subgroup than in the +LTG or -LTG/-CBZ
      subgroups (9%, 3%, and 3%, respectively). The overall incidence of SAEs in
      patients taking ESL was comparable across subgroups (+LTG, 5%; +CBZ, 6%; -LTG/
      CBZ, 5%). The results were similar when evaluating placebo-adjusted incidences.
      CONCLUSION: There was a potential pharmacodynamic interaction between AEDs with a
      putatively similar mechanism of action, with a seemingly lesser interaction
      between ESL and LTG versus ESL and CBZ. If combining ESL with LTG or CBZ,
      clinicians should be aware of the potential risk for an increased incidence of
      TEAEs typically associated with voltage-gated sodium channel inhibitors (e.g.,
      dizziness, blurred vision, vertigo, diplopia, headache, or vomiting).

PMID- 30278295
TI  - The association between multiple sleep-related characteristics and the metabolic
      syndrome in the general population: the New Hoorn study.
AB  - BACKGROUND: Previous studies have investigated the association between sleep
      duration, insomnia, day-time napping and metabolic syndrome individually, but
      never conjointly. In addition, the association with sleep medication use has yet
      to be investigated. We aimed to examine the associations between these sleep
      related characteristics and the metabolic syndrome, individually and conjointly,
      in a population-based cohort. MATERIAL AND METHODS: We used cross-sectional data
      of 1679 participants from the New Hoorn study, 52.6% women and age 60.8 + 6.4y.
      Sleep duration, insomnia, and day-time napping were measured using validated
      questionnaires. The use of sleep medication was documented by the registration of
      dispensing labels. The metabolic syndrome was defined according to ATP III.
      Linear and Poisson regressions were used, and all analyses were adjusted for age,
      sex, education level, job status, smoking, physical activity, depression and BMI.
      RESULTS: In our population-based cohort, 447 (26.6%) persons had the metabolic
      syndrome. Individual associations showed that, after correction, day-time napping
      for <=30 min and >30 min was associated with a prevalence ratio for the metabolic
      syndrome of 1.28 (95% CI: 1.1-1.5) and 1.74 (95% CI: 1.4-2.2), respectively,
      compared to participants who did not nap. Sleep duration, insomnia, and sleep
      medication use were not associated with the metabolic syndrome individually.
      However, conjointly analyses showed that, after correction, having >=2 sleep
      related characteristics was associated with a PR of 1.36 (95% CI: 1.0-1.8) of
      having the metabolic syndrome, compared to having no sleep-related
      characteristics. CONCLUSION: Sleep-related characteristics were associated with a
      higher prevalence of the metabolic syndrome in the general population.

PMID- 30278296
TI  - An analysis of the anatomic route of the hypoglossal nerve within the hypoglossal
      canal using dynamic computed tomography angiography in patients with anterior
      condylar arteriovenous fistulas.
AB  - OBJECTIVE: The venous outlet of anterior condylar arteriovenous fistulas (AC
      AVFs) often empties into the anterior condylar vein (ACV). Hypoglossal nerve
      palsy is one of the major complications after transvenous embolization (TVE) for
      the AC-AVF within the hypoglossal canal. However, no studies have investigated
      the route of the hypoglossal nerve within the hypoglossal canal in AC-AVF. The
      aim of the current study is to retrospectively verify the anatomical route of the
      hypoglossal nerve within its canal using dynamic computed tomography angiography
      (CTA) in order to facilitate the safe TVE for AC-AVF. PATIENTS AND METHODS: We
      included five patients with AC-AVF from 2011 to 2017. Dynamic CTA was performed
      on all patients. When the ACV was well-visualized by dynamic CTA, the hypoglossal
      nerve could be recognized as a less-intense structure within the surrounding
      enhanced vasculatures and the nerve route within the canal was analyzed. We also
      analyzed the location of the fistulas by digital subtraction angiography and cone
      beam computed tomography. RESULTS: In all five patients, the filling defect of
      the hypoglossal nerve ran through the most caudal portion of the hypoglossal
      canal. The fistulous pouches were located in the hypoglossal canal in three
      cases, and in the jugular tubercle venous complex in two cases. In all three
      cases with AC-AVF in the hypoglossal canal, the fistulous pouches were located in
      the superior wall of the hypoglossal canal, which means superior to the ACV. We
      performed TVE in four patients and none developed post-therapeutic hypoglossal
      nerve palsy. CONCLUSION: In the current study, dynamic CTA is useful for
      detecting the hypoglossal nerve within the hypoglossal canal. The hypoglossal
      nerve usually ran the bottom of its canal and the fistulous pouches were usually
      located at the superior aspect of the canal opposite side to the hypoglossal
      nerve. Accordingly, the selective embolization within the fistulous pouch located
      in the superior aspect of the ACV including jugular tubercle venous complex can
      reduce the risk of hypoglossal nerve palsy.

PMID- 30278297
TI  - Severity of intracranial carotid artery calcification in intracranial
      atherosclerosis-related occlusion treated with endovascular thrombectomy.
AB  - OBJECTIVES: Intracranial atherosclerosis related large vessel occlusions (ICAS-O)
      are challenging to diagnose and manage. The degree of intracranial carotid artery
      calcification may assist pre-thrombectomy diagnosis of ICAS and guide treatment
      strategy. The aim of the study is to determine if intracranial carotid
      calcification is associated with ICAS-O. PATIENTS AND METHODS: Consecutive large
      vessel occlusion patients who underwent thrombectomy from 2006 to 2017 were
      retrospectively studied. Patients were classified into ICAS-O if pre-existing
      atherosclerotic lesion was identified as the etiology for large vessel occlusion
      during the thrombectomy. The degree of intracranial carotid artery calcification
      (ICAC), technical and clinical outcomes of ICAS-O was compared with non-ICAS-O
      patients. RESULTS: In a retrospective cohort study of 64 thrombectomy patients,
      ICAS-O accounted for 14.1% of cases and was associated with higher degree of
      carotid calcification (mean Woodcock scale 2.8 vs 1.6, p = 0.044), need of stent
      retreiver rescue (55.6% vs 5.5%, p = 0.001), and adjuvant stenting or angioplasty
      (33.3% vs 0%, p = 0.002) compared with non-ICAS-O. CONCLUSION: The severity of
      ICAC may be associated with ICAS-O as the underlying etiology amongst
      thrombectomy patients. Compared with large vessel occlusion of other causes, ICAS
      O was associated with more failure of aspiration and a higher need of adjuvant
      stenting and angioplasty.

PMID- 30278298
TI  - Cerebrotendinous xanthomatosis presenting with extensive cerebral cortex
      symptoms: A case report.

PMID- 30278299
TI  - Relevance of KFLC quantification to differentiate clinically isolated syndrome
      from multiple sclerosis at clinical onset.
AB  - OBJECTIVE: The objective of the research was to evaluate diagnostic and
      predictive value for determination of KFLC in cerebrospinal fluid (CSF) compared
      to the qualitative procedure of OCB determination in patients with CIS who
      converted to MS during a two-year period. PATIENTS AND METHODS: KFLC, total
      immunoglobulin G (IgG), serum albumin and CSF albumin were determined with an
      immunonephelometric method in 151 patients with suspected MS who were admitted to
      the Neurology Clinic while CSF/serum quotients (QKFLC, QIgG and QAlb) and indexes
      were calculated with regards to albumin (QCSF/Qserum). Presence of OCBs was
      determined by isoelectric focusing with immunofixation. Based on their clinical,
      OCB and magnetic resonance imaging (MRI) findings, 50 patients were classified as
      other neurological disorder patients (OND), and 101 patients were classified as
      CIS, 50 of which converted to MS during the two-year period. ROC analysis, ROC
      curve comparisons and comparison of median KFLC parameters were used to find
      optimal cut-off with regards to CIS diagnosis and conversion to MS. RESULTS: CSF
      KFLC median was 2,01 mg/L in MS group contrary to 0,68 mg/L and 0,17 mg/L in CIS
      and OND group, and KFLC index was 33,52 mg/L contrary to 9,68 mg/L and 3,71 mg/L
      (p < 0,0001). ROC analysis for accuracy of detection of intrathecal synthesis for
      QKFLC and KFLC index showed an AUC of 0,891 and 0,839 and the cut-off of 0,027
      and 8,82, respectively (sensitivity 73,2% and 71,3%; specificity 96,0% and 98,0%;
      +PV 97,4% and 98,6%). The diagnostic accuracy of KFLC index for conversion from
      CIS to MS showed AUC of 0,840 and a cut-off of 9,092 (sensitivity 90,0%;
      specificity 73,3%; -PV 93,7%). Life age correlates significantly with serum KFLC
      (r = 0,34; p < 0,0001) and through aging process lower KFLC indexes can be
      expected, i.e. likelihood of false negative diagnoses. CONCLUSION: KFLC index
      showed diagnostic value, although it is not more specific and more sensitive than
      OCB. Application of KFLC might serve as a screening method while OCB could be
      used in uninterpretted cases only. Patients who converted to MS have
      significantly higher KFLC which can contribute to an early diagnosis and prompt
      therapy with its predictive role.

PMID- 30278300
TI  - Silver-Catalyzed Regio- and Stereoselective Formal Carbene Insertion into
      Unstrained C-C sigma-Bonds of 1,3-Dicarbonyls.
AB  - A regio- and stereoselective silver-catalyzed formal carbene insertion into 1,3
      dicarbonyls has been developed, using N-nosylhydrazones as diazo surrogates. Two
      new C-C bonds are constructed at the carbenic carbon center through the selective
      cleavage of the C-C(=O) sigma-bond of acyclic 1,3-dicarbonyls, enabling the
      preparation of various synthetically useful polysubstituted gamma-diketones,
      gamma-ketoesters, and gamma-ketoamides in high yields. The in situ formation of a
      donor-acceptor cyclopropane, via reaction of the enolate of the 1,3-dicarbonyl
      with an electrophilic silver carbenoid, is proposed as a key process in the
      catalytic cycle.

PMID- 30278301
TI  - Circulating levels of tissue factor and the risk of thrombosis associated with
      antiphospholipid syndrome.
AB  - The mechanisms behind the severe hypercoagulable state in antiphospholipid
      syndrome (APS) have not yet been fully elucidated. Knowledge on the etiology of
      thrombosis in APS is needed to improve treatment. We performed a case control
      study to evaluate the association of the levels of circulating tissue factor (TF)
      with thrombotic APS and unprovoked venous thromboembolism (VTE), as compared with
      controls without a history of thrombosis. Study participants were selected in the
      same geographic area. Linear regression was used to evaluate possible
      determinants of TF levels among controls and logistic regression was used to
      evaluate the association between TF, unprovoked VTE and t-APS. TF levels were
      grouped into three categories based on: below 50th percentile [reference],
      between 50-75th percentiles [second category] and 75th percentile [third
      category]. Two hundred and eighty participants were included in the study; 51
      patients with unprovoked VTE, 111 patients with t-APS and 118 control
      individuals. The levels of TF were not associated with an increased risk of
      unprovoked VTE, as compared with controls. The adjusted odds ratio for t-APS was
      2.62 (95%CI 1.03 to 6.62) with TF levels between 50-75th percentiles and 8.62
      (95%CI 3.76 to 19.80) with TF levels above the 75th percentile, as compared with
      the reference category (below the 50th percentile). In the subgroup analysis,
      higher levels of TF were associated with both arterial and venous thrombosis in
      APS and with both primary and secondary APS. Circulating TF is associated with
      thrombotic complications related to APS, but not with the risk of unprovoked VTE.

PMID- 30278302
TI  - Differences in muscular and perceptual responses to a neck/shoulder fatiguing
      task between women and men.
AB  - Fatigue is a risk factor for the development of work-related musculoskeletal
      disorders (WMSDs) of the neck/shoulder, and exertion is a state that connects the
      sensory/affective and physical aspects of fatigue. Relationships between ratings
      of perceived exertion (RPE) and electromyogram (EMG) signal characteristics have
      been identified. However, the sex-specific effects on these relationships are
      unclear and could be affected by personal factors such as skinfold thickness. 28
      healthy young adults completed a fatiguing task with the arm held at shoulder
      height. Neck/shoulder EMG and RPE were collected at the end of each minute. Males
      showed stronger correlations between RPE with anterior deltoid (AD, rs = 0.37)
      and upper trapezius (UT, rs = 0.48) EMG, whereas females showed a weak
      relationship between RPE and UT EMG (rs = 0.22), and no relationship with AD EMG.
      Significant correlations were observed between biceps EMG and skinfold thickness
      in both males and females. Findings suggest that neck/shoulder perceived exertion
      is strongly associated to the activity of shoulder mobilizers (anterior deltoid)
      in men, whereas in women, it is rather associated to the activity of shoulder
      stabilizers (upper trapezius), and to a lesser extent. It is possible that in
      turn, these sex differences affect fatigue adaptation strategies. Skinfold
      thickness may be an important variable to consider when studying sex-specific
      characteristics of muscle fatigue.

PMID- 30278303
TI  - Effect of drought stress on growth parameters, osmolyte contents, antioxidant
      enzymes and glycyrrhizin synthesis in licorice (Glycyrrhiza glabra L.) grown in
      the field.
AB  - Glycyrrhiza glabra L. (licorice) is a medicinal species rich in the specialised
      plant metabolite glycyrrhizin. It has been previously proposed that drought,
      which is increasing in importance due to the climatic change and scarcity of
      water resources, can promote the synthesis of glycyrrhizin. The effects of
      slight, moderate and intense drought (70, 35 and 23% of the regular irrigation,
      respectively) on growth parameters, osmolyte content, oxidative stress markers,
      antioxidant enzymes, glycyrrhizin biosynthesis genes and root glycyrrhizin
      concentration and contents, have been assessed in five Iranian licorice genotypes
      grown in the field. Drought decreased progressively biomass and leaf relative
      water contents, and increased progressively osmolyte (proline, glycine-betaine
      and soluble sugars) concentrations in leaves and roots. Drought caused oxidative
      stress in leaves, as indicated by lipid peroxidation and hydrogen peroxide
      concentrations, and increased the activities of antioxidant enzymes in leaf
      extracts (catalase, peroxidase, superoxide dismutase and pholyphenoloxidase).
      Drought promoted the synthesis of glycyrrhizin, as indicated by the increases in
      the expression of the glycyrrhizin biosynthesis pathway genes SQS1, SQS2, bAS,
      CYP88D6, CYP72A154 and UGT73, and increased the root concentrations of
      glycyrrhizin with drought in some genotypes. However, the large decreases in root
      biomass caused by drought led to general decreases in the amount of glycyrrhizin
      per plant with moderate and intense drought, whereas the slight drought treatment
      led to significant decreases in glycyrrhizin content in only one genotype. Under
      intense drought two of the genotypes were still capable to maintain half of the
      control glycyrrhizin yield, whereas in the other three genotypes glycyrrhizin
      yield was 22-33% of the control values. Results indicate that under intense
      drought, with only 23% of the normal water dose being applied, an appropriate
      choice of genotype can still lead to acceptable glycyrrhizin yields.

PMID- 30278304
TI  - Assembling actin filaments for protrusion.
AB  - Cell migration entails a plethora of activities combining the productive exertion
      of protrusive and contractile forces to allow cells to push and squeeze
      themselves through cell clumps, interstitial tissues or tissue borders. All these
      activities require the generation and turnover of actin filaments that arrange
      into specific, subcellular structures. The most prominent structures mediating
      the protrusion at the leading edges of cells include lamellipodia and filopodia
      as well as plasma membrane blebs. Moreover, in cells migrating on planar
      substratum, mechanical support is being provided by an additional, more
      proximally located structure termed the lamella. Here, we systematically dissect
      the literature concerning the mechanisms driving actin filament nucleation and
      elongation in the best-studied protrusive structure, the lamellipodium. Recent
      work has shed light on open questions in lamellipodium protrusion, including the
      relative contributions of nucleation versus elongation to the assembly of both
      individual filaments and the lamellipodial network as a whole. However, much
      remains to be learned concerning the specificity and relevance of individual
      factors, their cooperation and their site-specific functions relative to the
      importance of global actin monomer and filament homeostasis.

PMID- 30278305
TI  - Coping via substance use, internal attribution bias, and their depressive
      interplay: Findings from a three-week daily diary study using a clinical sample.
AB  - BACKGROUND: The relationship between depression and coping-oriented substance use
      is extensively documented; however, the cognitive processes moderating this
      bidirectional relationship are not well-understood. The present study
      investigated whether internal attribution bias coupled with a tendency to use
      drugs and/or alcohol to cope predicts increases in depression and daily-levels of
      general negative affectivity, sadness, and hostility. METHOD: Sixty-seven adults
      diagnosed with depression were recruited from out-patient treatment settings (66%
      female, 81% White, Mage = 31, SDage = 13.2). Participants completed measures on
      substance-related coping, depression, attributional style, and daily affect over
      a three-week period. RESULTS: Substance use to cope predicted increases in
      depression among individuals with high-level internal attribution bias. Further,
      coping via substance use moderated the relationship between internal attribution
      bias and daily-level sadness, such that sadness was highest among individuals
      with a high internal attribution bias coupled with greater levels of coping via
      substance use. A modest, yet, non-significant upward trend in daily-level
      hostility was also observed. CONCLUSIONS: Results suggested that depressed
      individuals who habitually perceive themselves as being responsible or
      blameworthy for negative life events are at an increased risk of worsening
      depressive symptoms and experiencing greater daily levels of sadness over a
      relatively brief period of time, particularly, when tending to engage in
      substance use as a mechanism to cope. This interaction effect can elicit greater
      daily-level sadness as well. Findings may aid in the identification and treatment
      of individuals at risk of maintaining or worsening their depressive symptoms.

PMID- 30278307
TI  - Environmental tobacco smoke exposure among electronic cigarette users.
AB  - INTRODUCTION: Exposure to environmental tobacco smoke (ETS) from combustible
      tobacco products causes various diseases and makes quitting smoking more
      difficult. However, little is known about exposure of e-cigarette users to ETS
      from combustible tobacco products. This study aimed to investigate e-cigarette
      users' exposure to ETS from tobacco smokers. METHODS: The association between ETS
      exposure frequency and different types of smokers including e-cigarette users was
      examined using ordered logistic regression analysis and nationally representative
      survey data on 28,765 individuals who were interviewed in the Canadian Tobacco,
      Alcohol and Drugs Surveys conducted during 2013 and 2015. Survey respondents were
      classified into one of five smoker types: smokers of tobacco only, dual users of
      tobacco and e-cigarettes, users of e-cigarette only, former smokers and never
      smokers. The analyses were conducted using the entire sample and by age group.
      RESULTS: Young to mid-age (15-54) dual users of both regular cigarettes and e
      cigarettes have higher ETS exposure than even tobacco smokers. Young to mid-age
      single users of e-cigarettes are less exposed to ETS than tobacco smokers, but
      still have higher ETS than never smokers. At older age (55+), both dual and
      single e-cigarette users face similar risks of ETS exposure as tobacco smokers.
      CONCLUSIONS: E-cigarette users are at high risk of ETS exposure. Policies that
      target the behaviour of e-cigarette users as well as the environments surrounding
      them to address their high ETS exposure risk would be beneficial.

PMID- 30278306
TI  - Implementing peer recovery services for overdose prevention in Rhode Island: An
      examination of two outreach-based approaches.
AB  - BACKGROUND: Rhode Island has the tenth highest rate of accidental drug overdose
      deaths in the United States. In response to this crisis, Anchor Recovery Center,
      a community-based peer recovery program, developed programs deploying certified
      Peer Recovery Specialists to emergency departments (AnchorED) and communities
      with high rates of accidental opioid overdoses (AnchorMORE). OBJECTIVES: The
      purpose of this paper is to describe AnchorED and AnchorMORE's activities and
      implementation process. METHODS: AnchorED data were analyzed from a standard
      enrollment questionnaire that includes participant contact information,
      demographics, and a needs assessment. The AnchorED program outcomes include
      number of clients enrolled, number of naloxone training sessions, and number of
      referrals to recovery and treatment services. Overdose deaths and naloxone
      distribution through AnchorMORE were mapped using Tableau software. RESULTS: From
      July 2016-June 2017, AnchorED had 1329 contacts with patients visiting an
      emergency department for reported substance misuse cases or suspected overdose.
      Among the contacts, 88.7% received naloxone training and 86.8% agreed to
      continued outreach with a Peer Recovery Specialist after their ED discharge. Of
      those receiving peer recovery services from the Anchor Recovery Community Center,
      44.7% (n = 1055/2362) were referred from an AnchorED contact. From July 2016-June
      2017, AnchorMORE distributed 854 naloxone kits in high-risk communities and
      provided 1311 service referrals. CONCLUSION: These findings indicate the
      potential impact peer recovery programs may have on engaging high-risk
      populations in treatment, overdose prevention, and other harm reduction
      activities. Additional research is needed to evaluate the reach of implementation
      and services uptake.

PMID- 30278308
TI  - Phosphodiesters quaternary ammonium nanoparticles as label-free light scattering
      probe for turn-off detection of tyrosine.
AB  - In this contribution, a new highly sensitive and selective sensor of the
      determination of tyrosine has been proposed based on the downturn effect of light
      scattering (LS) using phosphodiesters quaternary ammonium nanoparticles (PQANPs).
      Phosphodiesters quaternary ammonium (PQA), one of Gemini zwitterionic
      surfactants, self-aggregated into the micelle named as PQANPs, which generated
      strong LS signal in aqueous solution under the optimum condition. Interestingly,
      the powerful LS intensity of PQANPs with the maximum peak located at 391 nm
      significantly decreased after introducing trace amount of tyrosine. The decreased
      value of the LS intensity of the PQA-tyrosine system (DeltaILS) was in proportion
      to tyrosine concentration in the ranges from 5.5 * 10-8 mol/L to 4.68 * 10-6
      mol/L, with a detection limit of 1.38 * 10-8 mol/L. Based on this decreased LS
      situation, the novel approach of the determination of tyrosine was first
      developed. The reaction mechanism for the interaction between PQANPs and tyrosine
      was also investigated. Moreover, the proposed LS assay was applied to the
      detection of tyrosine concentration in human serum and urine samples with
      satisfactory results.

PMID- 30278309
TI  - Transitions within a safe road system.
AB  - As drivers move through the road transport system they are exposed to a range of
      different situations and road conditions in a relatively short space of time.
      Drivers' expectations about what will happen on different types of roads have
      strong effects on their speed choices, and where they look and what they attend
      to. As a result it is important to assist drivers to change their expectations
      when they transition from one road type to another. In this experiment we
      investigated the effectiveness of different centreline road markings in preparing
      for a horizontal curve as drivers moved from a motorway to a two-lane rural
      country road. Fifty individuals were recruited to participate in a video-based
      simulated driving task to compare three centreline marking types in terms of
      their effects on speed choice and reactions to a driving hazard (horizontal
      curve). Although a complex marking previously associated with high risk produced
      the largest speed reductions during the transition from the motorway, it was the
      centreline more traditionally associated with rural country roads (dashed white
      centreline) that was associated with the best hazard reactions post-transition
      (brake reaction time and speed reduction before a horizontal curve). The findings
      demonstrated that the look of a road needs to convey a clear and unambiguous
      message to drivers. The transition to a two-star rural road is best achieved by
      making the road look like a typical two-star road as soon as possible.

PMID- 30278310
TI  - Associations between repeated measures of maternal urinary phthalate metabolites
      during pregnancy and cord blood glucocorticoids.
AB  - BACKGROUND: Previous studies have suggested that phthalates might disrupt fetal
      steroidogenesis. However, the evidence of the effects of prenatal phthalate
      exposure across pregnancy on fetal glucocorticoids was insufficient. OBJECTIVE:
      We investigated the associations between urinary phthalate metabolites across
      pregnancy and cord blood glucocorticoids in a prospective birth cohort. METHODS:
      Our study included 553 mother-infant pairs from a prospective birth cohort
      conducted in Wuhan, China. Maternal urine samples were collected at 14, 24 and 36
      weeks of gestation (mean). Urinary phthalate metabolites and cord blood
      glucocorticoids (cortisol and cortisone) were measured. Generalized estimating
      equation models were conducted to explore the relationships of phthalate
      metabolite concentrations at each trimester and glucocorticoid levels. RESULTS:
      Among the participants, mono-benzyl phthalate (MBzP) in the first trimester was
      associated with higher cortisol/cortisone ratio concentrations, and mono-(2-ethyl
      5-carboxypentyl) phthalate (MECPP) and mono-(2-ethyl-5-oxohexyl) phthalate
      (MEOHP) measured in the third trimester were associated with decreased cortisone.
      Moreover, the associations between phthalates and glucocorticoids varied by sex.
      Among the female infants, each 10-fold increase in several maternal urinary
      phthalate metabolite concentrations in 1st and 3rd trimester was associated with
      the increased glucocorticoid levels with percent changes ranged from 16.2%-55.9%.
      However, among male infants, each 10-fold increase in maternal urinary MECPP,
      mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and MEOHP in 3rd trimester was
      associated with 20.8%-36.3% decreased cortisol and cortisone levels,
      respectively. CONCLUSION: We have shown that prenatal phthalate exposure during
      early and late trimester disrupted the infant steroidogenesis and these
      associations might be modified by infant sex. To the best of our knowledge, this
      is the first study to evaluate phthalate exposure at three trimesters during
      pregnancy in relation to infant glucocorticoids.

PMID- 30278311
TI  - Environmental styrene exposure and neurologic symptoms in U.S. Gulf coast
      residents.
AB  - BACKGROUND: Styrene is an established neurotoxicant at occupational levels, but
      effects at levels relevant to the general population have not been studied. We
      examined the neurologic effects of environmental styrene exposure among U.S. Gulf
      coast residents. METHODS: We used National Air Toxics Assessment (NATA) 2011
      estimates of ambient styrene concentrations to assign exposure levels for 21,962
      non-diabetic Gulf state residents, and additionally measured blood styrene
      concentration in a subset of participants (n = 874). Neurologic symptoms, as well
      as detailed covariate information, were ascertained via telephone interview. We
      used log-binomial regression to estimate prevalence ratios (PR) and 95%
      confidence intervals (95% CI) for cross-sectional associations between both
      ambient and blood styrene levels and self-reported neurologic symptoms. We
      estimated associations independently for ten unique symptoms, as well as for the
      presence of any neurologic, central nervous system (CNS), or peripheral nervous
      system (PNS) symptoms. We also examined heterogeneity of associations with
      estimated ambient styrene levels by race and sex. RESULTS: One-third of
      participants reported at least one neurologic symptom. The highest quartile of
      estimated ambient styrene was associated with one or more neurologic (PR, 1.12;
      95% CI: 1.07,1.18), CNS (PR, 1.17; 95% CI: 1.11,1.25), and PNS (PR, 1.16; 95% CI:
      1.09,1.25) symptom. Results were less consistent for biomarker analyses, but
      blood styrene level was suggestively associated with nausea (PR, 1.78; 95% CI:
      1.04, 3.03). In stratified analyses, we observed the strongest effects among non
      White participants. CONCLUSIONS: Increasing estimated ambient styrene
      concentration was consistently associated with increased prevalence of neurologic
      symptoms. Associations between blood styrene levels and some neurologic symptoms
      were suggestive. Environmental styrene exposure levels may be sufficient to
      elicit symptomatic neurotoxic effects.

PMID- 30278312
TI  - Molecular expression of Mg2+ regulator TRPM7 and CNNM4 in rat odontoblasts.
AB  - OBJECTIVE: Magnesium, the second most abundant cation in cellular fluid, is
      critical for mineralization of hard tissues. Among the molecules involved in
      cellular Mg2+ homeostasis, functional impairment of Mg2+ permeable ion channel
      TRPM7 or Mg2+ transporter CNNM4 have been found to result in severe
      hypomineralization of the enamel and dentin. However, molecular expressions of
      TRPM7, CNNM4 and their respective homologues have not been fully investigated in
      adult odontoblasts. DESIGN: Expressions of TRPM6, TRPM7, CNNM1, CNNM2, CNNM3,
      CNNM4 were screened in acutely dissociated rat odontoblasts by single cell RT
      PCR. Among these candidates, expression levels of TRPM7 and CNNM4 were compared
      along the odontoblast layer by immunohistochemical analysis. Finally, the
      coexpression pattern of TRPM7 and CNNM4 in subcellular regions was examined by
      immunocytochemical analysis. RESULTS: ScRT-PCR revealed high expression rate of
      TRPM7 and CNNM4 in odontoblasts, with CNNM4 detected almost exclusively in TRPM7
      positive odontoblasts. However, CNNM2 and CNNM3 were detected in only a small
      population of odontoblasts, and TRPM6 and CNNM1 were not detected even in the
      pulp tissue. Immunohistochemical analysis revealed higher CNNM4 expression in the
      apical odontoblast layer than the coronal area, in contrast to the ubiquitous
      expression of TRPM7. Lastly, immunocytochemical analysis revealed colocalization
      of CNNM4 with TRPM7 in the odontoblastic process. CONCLUSIONS: CNNM4 and TRPM7
      may serve as main Mg2+ regulators in odontoblasts, possibly with selective
      involvement of CNNM4 in apical dentin formation or mineralization. Colocalization
      of TRPM7 and CNNM4 in the odontoblastic process suggest functional coupling of
      these two molecules to maintain Mg2+ homeostasis.

PMID- 30278313
TI  - Selenium amelioration of arsenic toxicity in rice shows genotypic variation: A
      transcriptomic and biochemical analysis.
AB  - The toxic metalloid arsenic (As) is consumed mostly through contaminated rice.
      Therefore, reducing its accumulation and maintaining nutrient homeostasis in crop
      plants are imperative to ensure food safety. However, there is a dearth of
      information on the interrelationship between nutrient homeostasis and the
      regulatory mechanisms of arsenic-selenium (As-Se) interactive pathways
      responsible for stress tolerance. In the present study, experiments were
      conducted in hydroponically grown 12-day-old seedlings of rice (Oryza sativa L.)
      varieties (Pusa Basmati1 and IR64) treated with arsenite (AsIII) (150 MUM),
      selenium (SeVI) (20 MUM), and As + Se. It was observed that selenium
      supplementation ameliorated As toxicity by reducing its accumulation and
      retrieving As-induced nutrient deficiency. Significant decrease in As
      accumulation, H2O2 content, and fluorescent intensity of nitric oxide (NO),
      reactive oxygen species (ROS), and superoxide radical (O2.-) along with cell
      death with Se supplementation in both rice varieties demonstrated the protective
      role of Se as a probable ROS quencher. Addition of Se increased the enzyme
      activities of thiol metabolism and induced differential transcript accumulation
      patterns of sulfur-related genes. Nutrient level positively correlated with the
      differential expression pattern of NPK-related genes that play roles in
      metabolism and nutrient availability in both varieties. Though Pusa Basmati1
      (PB1) showed higher tolerance to As, IR64 overcomes As toxicity more efficiently
      than PB1 in the presence of Se, which highlights that IR64 is a better performer
      in the presence of Se. Overall, this study provides novel insight into the role
      of Se in As-stressed rice genotypes through alteration of nutrient transporters
      and thiol-related genes.

PMID- 30278314
TI  - Accumulation of water-soluble carbohydrates and gene expression in wheat stems
      correlates with drought resistance.
AB  - In order to understand the effects of sugar metabolism on drought resistance in
      wheat, two wheat cultivars with different levels of drought resistance were used
      in this study. We investigated the accumulation pattern of water-soluble
      carbohydrates (WSC) and expression profiles of twelve fructan metabolism-related
      genes in peduncle (PED), penultimate (PEN), and lower internode (LOW) stem
      tissues under drought stress. LH7, a higher drought-resistance cultivar,
      contained a higher stem dry weight and higher content of WSC in PED, PEN, and LOW
      tissues, while XN979, a lower drought-resistance cultivar, contained lower
      values. The tissues from LOW internodes had the highest WSC content, while PED
      had the lowest. The mRNA levels of genes encoding fructan synthesis-related
      enzymes, sucrose: sucrose 1-fructosyltransferase (1-SST), sucrose: fructan 6
      fructosyltransferase (6-SFT), and fructan: fructan 1- fructosyltransferase (1
      FFT) showed higher expression levels at early time points following stress,
      whilst the genes encoding degradation-related enzymes, fructan exohydrolases (1
      FEH), and invertase (INV), showed higher expression at a later time point.
      Compared with XN979, LH7 showed higher expression levels of genes encoding
      fructan synthesis-related enzymes at all growth stages, whilst the expression of
      1-FEH-W3, 6-FEH, and INV3 were higher at a later stage; these expression levels
      would benefit fructan accumulation and remobilization at early and later stages,
      respectively. Drought stress induced most of fructan metabolism related genes
      expression level decreasing in LH7 PED, but enhancing in LH7 LOW part at early
      time points following stress. The results confirm that there are complex,
      coordinated expression patterns of fructan synthesis- and degradation-related
      genes in stems under drought stress. In summary, 1-SST-A2, 6-SFT, 1-FFT-A, 1-FEH
      W3, 6-FEH, and INV3 play important roles in fructan accumulation. In addition,
      higher expression of genes related to fructan synthesis and degradation occurs
      during early and later stages of drought stress, respectively, enhancing the
      drought resistance of wheat cultivar LH7.

PMID- 30278315
TI  - GABA enhances physio-biochemical metabolism and antioxidant capacity of
      germinated hulless barley under NaCl stress.
AB  - The effects of exogenous gamma-aminobutyric acid (GABA) on the endogenous GABA
      metabolism and antioxidant capacity of germinated hulless barley (Hordeum vulgare
      L.) under NaCl stress were investigated. The results showed that all of the GABA
      treatments could alleviate the growth inhibition and oxidative damage by NaCl
      stress, with 0.5 mM being the most effective concentration. The GABA-treated
      barley seedlings exhibited a significantly higher content of endogenous GABA and
      other free amino acids, especially proline, which resulted from the changes in
      corresponding enzyme activity. The phenylalanine ammonia lyase (PAL), cinnamic
      acid 4-hydroxylase (C4H), and 4-coumarate coenzyme A ligase (4CL) activities also
      increased in GABA-treated barley, which led to higher total phenolic content and
      antioxidant capacity than that of the control barley. These results indicate that
      GABA treatment may be an effective way to relieve salt stress as it induces the
      accumulation of endogenous GABA and proline and total phenolic content, thus
      enhancing the antioxidant capacity.

PMID- 30278316
TI  - Transmission imaging with a programmable detector in a scanning electron
      microscope.
AB  - A new type of angularly selective electron detector for use in a scanning
      electron microscope is presented. The detector leverages a digital micromirror
      device (DMD) to take advantage of the benefits of two-dimensional (2D) imaging
      detectors and high-bandwidth integrating detectors in a single optical system.
      The imaging detector provides direct access to the diffraction pattern, while the
      integrating detector can be synchronized to the microscope scan generator
      providing access to a real space image generated by integrating (pixel-by-pixel)
      a portion of the diffraction pattern as quantitatively defined by the DMD. The
      DMD, in effect, takes the place of the objective aperture in a transmission
      electron microscope (TEM) or an annular detector in a scanning transmission
      electron microscope (STEM), but has the distinct advantage that it can be
      programmed to take any shape in real time. Proof-of-principle data collected with
      the detector show diffraction contrast in samples ranging from a polycrystalline
      gold film to monolayer graphene.

PMID- 30278317
TI  - Ferroelectric properties and piezoresponse force micoroscopy study of Bi3TaTiO9
      thin films.
AB  - We investigate the ferroelectric properties and crystal structures of Bi3TaTiO9
      (BTTO) thin films deposited on single-crystal Nb-doped (100) SrTiO3 substrates
      via pulsed laser deposition. The BTTO films exhibited either a (001)-epitaxial
      crystalline structure or a mixed a- and c-oriented polycrystalline structure
      depending on the substrate temperature. The ferroelectric polarization and
      piezoelectric coefficient of the mixed a- and c-oriented film were larger than
      those of the (001)-epitaxial film because its polar axis was perpendicular to the
      c-axis. Vertical and lateral piezoresponse force microscopy studies indicate that
      the ferroelectric domains of the (001)-epitaxial film were all parallel to the in
      plane orientation, whereas the mixed a- and c-oriented film comprised both square
      grains with in-plane-oriented ferroelectric domains and longish grains with
      ferroelectric domains out of orientation with the plane.

PMID- 30278318
TI  - Atomic resolution force imaging through the static deflection of the cantilever
      in simultaneous Scanning Tunneling/Atomic Force Microscopy.
AB  - We report simultaneous Force -static deflection of the cantilever-, Force
      Gradient and Scanning Tunneling topography images of Si(111)(7 * 7) surface using
      an off-resonance small amplitude non-contact atomic force microscopy technique
      with improved force sensitivity. The signal-to-noise ratio of the fiber
      interferometer used to detect the deflections of the cantilever was improved by
      applying an RF-modulation into the diode laser, which suppresses the noise in the
      laser. The measured sensitivity of ~20 fm/?Hz allows us to obtain atom resolved
      images of the surface in static deflection of the cantilever, simultaneously with
      the other imaging channels.

PMID- 30278319
TI  - Rapid and longer-term antidepressant effects of repeated-dose intravenous
      ketamine for patients with unipolar and bipolar depression.
AB  - OBJECTIVE: Single-dose intravenous (IV) injection of ketamine has shown rapid but
      transient antidepressant effects. The strategy of repeated-dose ketamine
      infusions to maintain antidepressant effects has received little systematic
      study. This study was conducted to examine the efficacy and tolerability of six
      ketamine infusions in Chinese patients with unipolar and bipolar depression.
      METHODS: Ninety seven patients with unipolar (n = 77) and bipolar (n = 20)
      depression received repeated ketamine infusions (0.5 mg/kg over 40 min) with
      continuous vital sign monitoring. Depressive symptoms were measured by the
      Montgomery-Asberg Depression Rating Scale (MADRS). Suicidal ideation was assessed
      using the Scale for Suicidal Ideations (SSI)-part 1. Anxiety symptoms were
      evaluated with the 14-item Hamilton Anxiety Scale (HAMA). Adverse
      psychopathological and dissociative effects were assessed using the Brief
      Psychiatric Rating Scale (BPRS)-positive symptoms and Clinician Administered
      Dissociative States Scale (CADSS), respectively. Patients were assessed at
      baseline, 4 and 24 h, and 3, 4, 5, 6, 8, 9, 10, 11, 12, 13 and 26 days. RESULTS:
      After six ketamine infusions, the response and remission rates were 68.0% and
      50.5%, respectively. There were significant decreases in MADRS, SSI-part 1, and
      HAMA scores within four hours following the first ketamine infusion, and the
      decreases were sustained over the subsequent infusion period. The nonresponder
      subgroup manifested rapid significant improvement in suicidal ideations
      throughout the course of treatment. After the six ketamine infusions, the
      response was positively associated with the response at 24 h after the first
      infusion (OR = 8.94), personal income >=4000 yuan/month (OR = 3.04), and no
      history of psychiatric hospitalization (OR = 3.41). Only CADSS scores had a mild
      but marginally significant increase after the first infusion but with a
      significant BPRS score decrease. CONCLUSION: Six ketamine infusions were safe and
      effective in patients with unipolar and bipolar depression. The rapid and robust
      antidepressant and antisuicidal effects of ketamine infusion within four hours
      were sustained following the subsequent infusions.

PMID- 30278320
TI  - Internalizing symptoms and dating violence perpetration in adolescence.
AB  - BACKGROUND: Increasing evidence suggests an association between internalizing
      symptoms and violence against others. It remains unknown whether this link exists
      in the context of romantic relationships. In the current study, we tested whether
      anxiety and depression were associated over time with adolescent dating violence
      perpetration. METHODS: The sample included 238 Canadian adolescents (42% boys).
      Using a longitudinal design, their anxiety, depressive symptoms, and dating
      violence perpetration were annually assessed from age 14 to 15 years. RESULTS:
      Cross-lagged analyses revealed effects from anxiety and depressive symptoms to
      dating violence one year later (beta = 0.27, p < .001; and beta = 0.14, p = .04,
      respectively). No reversed cross-lagged paths were found from dating violence to
      subsequent anxiety or depression. CONCLUSIONS: Our findings underscore the
      predictive value of internalizing symptoms on dating violence perpetration.
      Reducing internalizing symptoms and improving coping strategies are important
      targets for the prevention of dating violence.

PMID- 30278322
TI  - High delusional ideation is associated with false pictorial memory.
AB  - BACKGROUND AND OBJECTIVES: To assess the relationship between false memories and
      schizotypal experiences in healthy volunteers. Previous research has examined a
      number of schizotypal dimensions and experiences and found a variety of results.
      Our aim was to determine the specificity of these associations by giving
      participants a schizotypy measure which tapped positive, negative and
      disorganised dimensions (O-LIFE) and another which focused on delusional ideation
      (PDI). METHODS: A new memory task was used consisting of images of everyday
      items, separated into categories. At test participants were presented with
      pictures which had been seen in the study phase, related lures (additional items
      from the same categories but which were new) and new items which were not from
      these categories. RESULTS: Positive correlations were found between scores on the
      positive dimension of schizotypy/delusional ideation and proportion of false
      memories. Moreover, these participants also had a greater tendency to respond
      with the highest confidence old response, regardless of the status of the item.
      No significant correlations were found with the other dimensions of schizotypy.
      LIMITATIONS: The confidence finding differs somewhat from previous research,
      which has found more confidence in memory errors and less confidence in correct
      responses in schizophrenia. It is unclear the reason(s) for this discrepancy.
      CONCLUSIONS: Increased false memory is associated with the positive dimension of
      schizotypy and delusional ideation and not the disorganised or negative
      dimensions. Furthermore, our results suggest that those high in positive
      schizotypy/delusional ideation require less evidence before they are willing to
      call an item old.

PMID- 30278321
TI  - Social media social comparison and identity distress at the college transition: A
      dual-path model.
AB  - INTRODUCTION: Social media provide a convenient platform for social comparison,
      an activity that should play an important role in youth's identity development at
      the transition to college. Yet, the identity implications of online social
      comparison have not been thoroughly explored. Drawing on the theories of social
      comparison, introspective processes, and identity distress, we examined a dual
      path model. The paths from two types of social media social comparison (i.e.,
      comparison of ability and comparison of opinion) to two introspective processes
      (i.e., rumination and reflection) and finally to identity distress were tested.
      METHODS: Short-term longitudinal survey data were collected from 219 college
      freshmen at a state university in the United States of America (Mage = 18.29,
      S.D. = 0.75; 74% female; 41% White, 38% Black). RESULTS: Social comparison of
      ability on social media had a positive association with concurrent rumination,
      which predicted higher identity distress. In contrast, social comparison of
      opinion on social media had a positive relationship with concurrent reflection,
      which, however, did not predict identity distress. CONCLUSION: Results indicate
      that different types of online social comparison yield distinct implications for
      young people's identity development. Largely, the study reaffirms the recently
      rising call for distinguishing the competition-based social comparison of ability
      from the information-based social comparison of opinion. At the same time, the
      study expands current knowledge of why these forms of social comparison may lead
      to differential outcomes, namely through the type of introspection they induce.

PMID- 30278323
TI  - A multidimensional analytical approach based on time-decoupled online
      comprehensive two-dimensional liquid chromatography coupled with ion mobility
      quadrupole time-of-flight mass spectrometry for the analysis of ginsenosides from
      white and red ginsengs.
AB  - Here, time-decoupled comprehensive two-dimensional ultra-high liquid
      chromatography (UHPLC) coupled with an ion mobility (IM)-high resolution mass
      spectrometer (HRMS) was established and used to analyze ginsenosides from the
      main roots of white ginseng (WG) and red ginseng (RG), which enabled the
      separation of complex samples in four dimensions (2D-LC, ion mobility, and mass
      spectrometry). The incompatibility of mobile phases, dilution effect, and long
      analysis time, which are the main shortcomings of traditional comprehensive 2D-LC
      methods, were largely avoided in this newly established 2D-UHPLC method. The
      orthogonality of this system was 55%, and the peak capacity was 4392. Under the
      optimized 2D-UHPLC-IM-MS method, 201 ginsenosides were detected from white and
      red ginseng samples. Among them, 10 pairs of co-eluting isobaric ginseng saponins
      that were not resolved by 2D-UHPLC-HRMS were further resolved using 2D-UHPLC-IM
      MS. In addition, 24 ginsenoside references were analyzed by UHPLC-IM-MS to obtain
      their collision cross section (CCS) values and ion mobility characteristics.
      Finally, the established new method combined with multivariate statistical
      analysis was successfully applied to differentiate WG and RG, and 9 ginsenosides
      were found to be the potential biomarkers by S-Plot and the values of max fold
      change, which could be used for classifying WG and RG samples. Overall, the
      obtained results demonstrate the applicability and potential of the established
      time-decoupled online comprehensive 2D-UHPLC-IM-MS system, and it will be
      extended to the analysis of other targeted or untargeted compounds, especially co
      eluting isomers in more herbal extracts.

PMID- 30278324
TI  - Determination of total and free ceftolozane and tazobactam in human plasma and
      interstitial fluid by HPLC-UV.
AB  - Ceftolozane/tazobactam is a new cephalosporin/beta-lactamase inhibitor
      combination. An HPLC-UV method is described for the determination of total and
      free ceftolozane and tazobactam in human plasma and in microdialysate of
      subcutaneous tissue, respectively. Separation was performed using a reversed
      phase column with phosphate buffer/acetonitrile as eluent and photometric
      detection at 260 nm (ceftolozane) or 220 nm (tazobactam). Linearity has been
      shown down to ceftolozane/tazobactam 0.1/0.05 mg/L in plasma and 0.03/0.015 mg/L
      in saline, respectively. The plasma protein binding of both drugs as determined
      by ultrafiltration was less than 10%. Temperature, pH or relative centrifugation
      force (up to 3000 x g) had no significant impact on the protein binding. The
      method was applied to the determination of ceftolozane and tazobactam in plasma
      and interstitial fluid of healthy volunteers following intravenous infusion of
      ceftolozane/tazobactam 1.0/0.5 g.

PMID- 30278325
TI  - Single vial cold kits optimized for preparation of gastrin releasing peptide
      receptor (GRPR)-radioantagonist 68Ga-RM2 using three different 68Ge/68Ga
      generators.
AB  - 68Ga-RM2 is a gastrin releasing peptide receptor (GRPR) antagonist PET (positron
      emission tomography) radiotracer which is being investigated in clinical trials
      as a potential prostate cancer imaging agent. Simple, one-step kit formulation of
      68Ga-RM2 would facilitate multicentre trials and allow easier integration in
      hospital radiopharmacy. Herein we report development of three sets of single-vial
      RM2 cold kits validated for formulation with three respective 68Ge/68Ga
      generators eluted in 0.6 M, 0.1 M and 0.05 M HCl (hydrochloric acid). Cold kits
      of varied pH (2, 3, 4 and 5) were prepared using 2 M sodium acetate for three
      different 68Ge/68Ga generators to determine influence of pH on the radiochemical
      yield of 68Ga-RM2. Buffer content was optimized with respect to volume of 68GaCl3
      eluate to be added (1 mL/2 mL/ 5 mL). Sterility, apyrogenicity and long term
      stability of cold kits; in vitro and serum stability of 68Ga-RM2 were
      investigated. In vitro cellular uptake and inhibition studies were performed to
      demonstrate the specificity of kit-formulated 68Ga-RM2. The radiochemical yield
      of 68Ga-RM2 formulated from three different generators was observed to be maximum
      at pH 3 (99 +/- 0.5%). Cold kits stored for 6 months at 0  degrees C also
      resulted in high radiochemical yield. 68Ga-RM2 exhibited excellent in vitro
      stability (1 h) and serum stability (1 h). In vitro cellular uptake of 5 +/- 0.8%
      in PC3 cells with >85% inhibition was observed for the 68Ga-RM2 radiotracer
      indicating its specificity towards GRPR expression. These simple, robust kits
      shall allow hospitals with different generators to participate in clinical
      studies of 68Ga-RM2 for screening of GRPR-expressing prostate tumors.

PMID- 30278326
TI  - Kinetics of spontaneous water-N2 imbibition in carbon molecular sieves.
AB  - In this study, a new kinetic model of spontaneous liquid-gas imbibition (SLGI)
      for microporous adsorbents has been developed. With three carbon molecular sieves
      (CMS) as adsorbents, N2 as gas probe and water as liquid probe, the kinetics of
      spontaneous water-N2 imbibition in CMS has been investigated at atmospheric
      pressure, and the applicability of the kinetic model to the SLGI has been
      assessed. The influences of the particle size of CMS and the experimental
      temperature in the range of 20-35  degrees C on the imbibition process have been
      analyzed based on the kinetic model. The relations between the kinetic parameters
      of the SLGI and the microporous parameters of the CMS obtained by CO2 adsorption
      at 273 K have been elucidated. The results indicate that the imbibition process
      is controlled by the diffusion of the water molecules into and N2 out of the
      micropores and the adsorption of the water on the pore surface of the CMS. The
      equilibrium gas recovery is positively related with the micropore volume, and the
      gas recovery rate depends mainly on the micropore size of the CMS.

PMID- 30278327
TI  - Magnetic nano-nets for capture of microbes in solution based on physical contact.
AB  - Self-assembly of Au nanoparticles with Fe ions is used to develop magnetic nano
      nets similar to fishing nets for capture and removal of microbes in aqueous
      medium. The nano-nets have a high aspect ratio, span microns in length with
      openings of 80-300 nm. This allows them to sample the liquid medium even at low
      volume fraction and also entrap the microbes in the solution. The nets and the
      trapped microbes can be effectively pulled from the solution by using an off the
      shelf magnet. Since the capture is based on physical contact, the nano-nets
      overcome the ability of the microbes to develop resistance to the cytotoxic
      effects of chemical compounds and nanomaterials. Using the nano-nets an absolute
      inactivation of 0.9 is achieved in 5 min. in a non-deaerated solution with
      Escherichia coli (E. coli). Further the removal of the nano-nets along with the
      captured microbes also predominantly eliminates the nanomaterial from the aqueous
      medium for future use.

PMID- 30278328
TI  - Shape-controlled synthesis of well-dispersed platinum nanocubes supported on
      graphitic carbon nitride as advanced visible-light-driven catalyst for efficient
      photoreduction of hexavalent chromium.
AB  - Photocatalytic degradation of environmental pollutants by using semiconductor
      based photocatalysts offers great potential for remediation of toxic chemicals.
      For an economical and eco-friendly method to eliminate hexavalent chromium
      (Cr(VI)), favourable catalysts own high efficiency, stability and capability of
      harvesting light. Combination of metal with semiconductor is a promising route to
      improve the photocatalytic performance for Cr(VI) reduction. Herein, well
      dispersed platinum (Pt) nanocubes (NCs) were synthesized by a facile one-step
      hydrothermal method with poly-l-lysine (PLL) as the growth-directing agent,
      followed by their uniform dispersion on graphitic carbon nitride (g-C3N4). Their
      morphology, crystal structure, chemical composition, and formation mechanism were
      mainly characterized by transmission electron microscopy (TEM), X-ray
      photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The hybrid
      nanocomposite was further explored for photocatalytic reduction of Cr(VI) to
      trivalent chromium (Cr(III)) under visible light at room temperature, by using
      formic acid (HCOOH) as a reducing agent, showing great improvement in
      photocatalytic activity and reusability, outperforming the referenced g-C3N4 and
      home-made Pt black/g-C3N4 catalysts. The effects of various experimental
      parameters and the proposed mechanism are discussed in detail.

PMID- 30278329
TI  - Facile approach to develop durable and reusable superhydrophobic/superoleophilic
      coatings for steel mesh surfaces.
AB  - Oil spills on the surfaces of bodies of water are now a great concern as they
      affect marine creatures and the ecosystem. Therefore, a facile technique for
      removal of oil from water is of much interest. In this study, superhydrophobic
      and superoleophilic coating is synthesized on stainless steel mesh via chemical
      etching using a mixture of FeCl3 and HCl followed by treatment with
      hexadecyltrimethoxysilane. Surface morphology analysis shows the presence of
      flower like microstructures on the surface after treatment. Superhydrophobic and
      superoleophilic properties have been achieved on stainless steel mesh with water
      static contact angle of 167 degrees  +/- 3 degrees , water tilting angle of 6
      degrees  +/- 1 degrees , and oil static contact angle of nearly 0 degrees . The
      coating shows excellent thermal, chemical and mechanical stability. Kerosene
      water and hexane-water mixtures were successfully separated via a simple
      filtering process using coated steel mesh with a separation efficiency of more
      than 98%. This approach can be implemented on any shape or size of stainless
      steel mesh and will have industrial applications.

PMID- 30278330
TI  - Controllable construction of multishelled p-type cuprous oxide with enhanced
      formaldehyde sensing.
AB  - Hollow metal oxide semiconductor (MOS) materials with controllable shells have
      attracted increasing attention because of their interesting properties and
      potential applications in sensors, catalysis, biology, etc. Cuprous oxide (Cu2O),
      which is a typical p-type semiconductor material, has four kinds of
      nanostructures (i.e., single-, double-, triple-, and quadruple-shelled spheres)
      and was successfully synthesized by the simple regulation of hexadecyl trimethyl
      ammonium bromide (CTAB) concentration. All as-obtained samples were at the
      nanometer level, and the hollow layers were also located between the two shells
      of the Cu2O nanostructures. The structural evolution and formation mechanism of
      the core-in-hollow multishelled nanostructure were also studied in this work.
      Moreover, the gas sensing performance of four kinds of materials was measured.
      The performance of the quadruple-shelled Cu2O-based formaldehyde (HCHO) sensor
      was greater than that of other sensors. The results indicated that the well
      defined multishelled structure may significantly enhance HCHO detection by
      facilitating the gas adsorption quantity and transport rate.

PMID- 30278331
TI  - Rescuing the CFTR protein function: Introducing 1,3,4-oxadiazoles as
      translational readthrough inducing drugs.
AB  - Nonsense mutations in the CFTR gene prematurely terminate translation of the CFTR
      mRNA leading to the production of a truncated protein that lacks normal function
      causing a more severe form of the cystic fibrosis (CF) disease. About 10% of
      patients affected by CF show a nonsense mutation. A potential treatment of this
      alteration is to promote translational readthrough of premature termination
      codons (PTCs) by Translational Readthrough Inducing Drugs (TRIDs) such as PTC124.
      In this context we aimed to compare the activity of PTC124 with analogues
      differing in the heteroatoms position in the central heterocyclic core. By a
      validated protocol consisting of computational screening, synthesis and
      biological tests we identified a new small molecule (NV2445) with 1,3,4
      oxadiazole core showing a high readthrough activity. Moreover, we evaluated the
      CFTR functionality after NV2445 treatment in CF model systems and in cells
      expressing a nonsense-CFTR-mRNA. Finally, we studied the supramolecular
      interactions between TRIDs and CFTR-mRNA to assess the biological
      target/mechanism and compared the predicted ADME properties of NV2445 and PTC124.

PMID- 30278332
TI  - Transformation of asiatic acid into a mitocanic, bimodal-acting rhodamine B
      conjugate of nanomolar cytotoxicity.
AB  - Based on their biological activity natural products continue to represent optimal
      lead structures for the development of novel drug candidates. We focused on the
      syntheses of several derivatives of the triterpene asiatic acid and on the
      evaluation of their cytotoxic activity in a photometric sulforhodamin B assay.
      Especially, benzamide 2 and rhodamine B conjugate 11 show a distinct cytotoxicity
      for several human tumor cell lines, e.g. EC50 (A2780) = 110 +/- 1 nM and EC50
      (A2780) = 8 +/- 2 nM, respectively. Interestingly, compound 11 showed for two
      human tumor cell lines (HT29 and 518A2) non-linear, bimodal dose-response
      relationships.

PMID- 30278333
TI  - Development of high potent and selective Bcl-2 inhibitors bearing the structural
      elements of natural product artemisinin.
AB  - By taking advantage of the apoptosis-inducing capacity of artemisinin
      derivatives, we developed several series of compounds by merging the basic
      structural elements of the natural product artemisinin into the P2 interaction
      pocket of the clinically prescribed Bcl-2 inhibitor venetoclax. Most of the new
      compounds displayed improved biochemical potency against Bcl-2 and high
      selectivity over Bcl-xL. Specifically, compounds 27c and 34c were found to be the
      most potent with IC50 values less than 2.0 nM. Unfortunately, these compounds
      only showed moderate antiproliferative effects against Bcl-2 dependent cells.
      Though further structural optimization is needed to improve the cellular
      absorptive permeability, the current approach represents an alternative strategy
      to develop novel Bcl-2 inhibitors with greater selectivity over Bcl-xL, which is
      related to the off-target adverse effects of venetoclax.

PMID- 30278334
TI  - The role of universities in attracting male students on to pre-registration
      nursing programmes: An electronic survey of UK higher education institutions.
AB  - The UK nursing workforce is facing a crisis. More nurses are leaving than
      entering the profession, and there are tens of thousands of unfilled vacancies.
      Political factors are having a significant impact on numbers, in particular the
      decision to withdraw bursaries for nursing undergraduates, and a steep decline in
      EU nurses registering to work in the UK post-Brexit. Against this backdrop, there
      is a stark gender imbalance in the workforce, with only around 11% of registered
      nurses being male. We surveyed UK higher education institutions to try to
      identify whether the gendered nature of nursing was considered a concern and
      whether steps were being taken to address it. We sent an electronic survey to
      every UK university offering undergraduate nurse training validated by the
      Nursing and Midwifery Council (NMC). With a response rate of 42%, the majority of
      respondents felt that nursing departments should take much more responsibility to
      increase the proportion of male nurses entering the nursing profession. More
      needs to be done to diversify the workforce and make nursing an appealing career
      choice for men and women.

PMID- 30278335
TI  - Feed-forward: Paving ways for students' subsequent learning.
AB  - BACKGROUND: Written feedback assists students in refining their future academic
      work. However, students prefer having feed-forward instead of feedback by their
      instructors that are the comments provided to them on drafts prior to the actual
      assignment submission. The current literature describes two common ways to convey
      feed-forward: the foremost one is on outlines while the second is on drafts.
      However, no existing literature had been found yet for sufficient guidance on the
      ideal approach of feed-forward to facilitate students' subsequent learning.
      DESIGN: A Quasi-experimental study design was employed to determine the
      effectiveness of feed-forward on outline versus drafts. SETTING: Study was
      conducted in a private nursing institution in Karachi, Pakistan. PARTICIPANTS:
      118 third-year undergraduate nursing students participated in the study. METHODS:
      Using consecutive sampling, 118 students were enrolled and equally divided in to
      two groups, each comprising of 59 students in the control and intervention arm.
      Control group received feed-forward through standard practice i.e. on their
      assignment outline while the intervention group received feed-forward on the
      draft of their scholarly paper. RESULTS: The performance of intervention arm had
      an upper hand over that of control wing as portrayed by their increased overall
      assignment and academic writing scores (of students on IELTs bands). The set
      outcomes also reflected better results in terms of the (reduced) frequency of
      visits to their instructors for clarification of written feedback. All in all,
      this research deduced that feed-forward on drafts is far more beneficial in
      contrast to that on an outline as it reinforces students' learning. CONCLUSION:
      The study findings affirmed that feed-forward is a useful strategy to enhance
      students' subsequent learning.

PMID- 30278336
TI  - Incomplete uptake of EGFR mutation testing and its impact on estimation of
      mutation prevalence in patients with non-squamous NSCLC: A population-based study
      in New Zealand.
AB  - BACKGROUND: Epidermal Growth Factor Receptor (EGFR) mutation testing is
      recommended for patients with non-squamous non-small cell lung cancer (NSCLC) but
      not all eligible patients get tested, which may bias the mutation prevalence
      estimated. This study aims to examine trends in the uptake of EGFR mutation
      testing in patients with non-squamous NSCLC in New Zealand; to develop a
      composite metric that quantifies the influences of demographic and clinico
      pathological factors on the testing uptake; and to estimate the prevalence of
      EGFR mutation if all patients were tested. METHODS: This population-based study
      involved all patients who were diagnosed with non-squamous NSCLC in four health
      regions in New Zealand between January 2010 and December 2015. Eligible patients
      were identified from the New Zealand Cancer Registry and information on EGFR
      mutation testing was obtained through linkage to TestSafe, a clinical information
      sharing service, and laboratory records. RESULTS: Of 2701 eligible patients, 1059
      (39.2%) were tested for EGFR mutation. The testing prevalence increased (3.7% in
      2010 to 64.6% in 2014) and the influences of demographic and clinic-pathological
      factors decreased from 2010 to June 2014, and remained stable afterward. Of the
      tested patients, 229 (21.6%) were mutation positive with a decreasing trend
      observed from 2010 (43.8%) to June 2014 (16.8%). The best-fit log-linear model
      estimated the prevalence of EGFR mutation, if all patients were tested, as 15.5%
      (95% CI: 13.2%-18.0%). CONCLUSION: The methods described here allowed a more
      accurate estimation of the prevalence of EGFR mutation.

PMID- 30278337
TI  - Knowledge and practice of computed tomography exposure parameters amongst
      radiographers in Jordan.
AB  - OBJECTIVE: To investigate the knowledge and practice of computed tomography (CT)
      radiographers working in Jordan. MATERIALS AND METHODS: This Institutional Review
      Board (IRB) approved study disseminated a questionnaire via social media and
      recruited 54 Jordanian CT radiographers. The questionnaire comprised 36 questions
      divided into four sections: demographics; an evaluation of knowledge regarding CT
      exposure; modifications to CT exposure for paediatric patients; dose units and
      diagnostic reference levels (DRLs). Descriptive and inferential statistics
      including Chi-square tests, Mann-Whitney U tests, independent samples t-tests and
      Kruskal-Wallis H tests were employed. Statistical significance was considered
      below p < 0.05. RESULTS: The 54 participants had various qualifications, with the
      majority holding a Bachelor's degree (n = 35, 64.8%) and the rest holding a
      Diploma (n = 19, 35.2%). In order to pass the questionnaire, participants needed
      to score 13 correct answers. The overall number of radiographers who correctly
      passed the questionnaire was 48 (88.9%). None of the participants correctly
      stated all the DRL values for chest, abdomen and brain CT. However, four out of
      54 respondents (7.4%) knew the chest DRL value, three (5.6%) participants
      correctly estimated the abdominal DRL value but only two (3.7%) knew the DRL for
      the brain. CONCLUSION: Good general knowledge was found amongst radiographers
      regarding the relationship of each exposure parameter to the image quality and
      patient dose. However, there was poor knowledge of diagnostic reference levels
      and the order of the organ radiation sensitivity. The need for CT radiographers
      to undertake further education that focuses on radiation exposure in CT is
      highlighted.

PMID- 30278338
TI  - Measuring and monitoring emotional changes in children who stutter.
AB  - The assessment of clients with speech disorders presents challenges for speech
      language pathologists. For example, having a reliable way of measuring the
      severity of the case, determining which remedial program is aligned with a
      patient's needs, and measuring of treatment processes. There is potential for
      brain-computer interface (BCI) applications to enhance speech therapy sessions by
      providing objective insights and real-time visualization of brain activity during
      the sessions. This paper presents a study on emotional state detection during
      speech pathology. The goal of this study is to investigate affective-motivational
      brain responses to stimuli in children who stutter. To this end, we conducted an
      experiment that involved recording frontal electroencephalography (EEG) activity
      from fifteen children with stuttering whilst they looked at visual stimuli. The
      contribution of our study is to provide a comprehensive background and a
      framework for emotional state detection experiments as assessment and monitoring
      tool in speech pathology. It mainly discusses the feasibility and potential
      benefits of applying EEG-based emotion detection in speech-language therapy
      contexts of use. The findings of our research indicate that emotional recognition
      using non-invasive EEG-based BCI system is sufficient to differentiate between
      affective states of individuals in treatment contexts.

PMID- 30278339
TI  - Prognostication of metastatic death in uveal melanoma patients: A Markov multi
      state model.
AB  - BACKGROUND/AIMS: Uveal melanoma is fatal in almost 50% of patients. We previously
      developed a prognostic model to predict all-cause mortality. The aim of this
      study was to improve our model by predicting metastatic death as a cause-specific
      event distinct from other causes of death. METHODS: Patients treated in Liverpool
      were included if they resided in England, Scotland or Wales and if their uveal
      melanoma involved the choroid. They were flagged at the National Health Service
      Cancer Registry, which automatically informed us of the date and cause of death
      of any deceased patients. A semiparametric Markov multi-state model was fitted.
      Two different baseline hazard rates were assumed, with state transition-specific
      covariates. For both failure types, age at treatment and sex were used. For the
      metastatic death case, these factors were added: anterior margin position,
      largest basal tumour diameter, tumour thickness, extra-ocular extension, presence
      of epithelioid melanoma cells, presence of closed connective tissue loops,
      increased mitotic count, chromosome 3 loss, and chromosome 8q gain. Missing data
      required a multiple-imputation procedure. RESULTS: The cohort comprised 4161
      patients, 893 of whom died of metastastic disease with another 772 dying of other
      causes. The optimism-corrected, bootstrapped C-index for metastatic death
      prediction was 0.86, denoting very good discriminative performance. Bootstrapped
      calibration curves at two and five years also showed very good performance.
      CONCLUSIONS: Our improved model provides reliable, personalised metastatic death
      prognostication using clinical, histological and genetic information, and it can
      be used as a decision support tool to individualize patient care in a clinical
      environment.

PMID- 30278340
TI  - A novel electrochemical aptasensor based on nontarget-induced high accumulation
      of methylene blue on the surface of electrode for sensing of alpha-synuclein
      oligomer.
AB  - This study describes a novel electrochemical aptasensor for detection of alpha
      synuclein (alpha-syn) oligomer, an important biomarker related to Parkinson's and
      Alzheimer's diseases. The sensing platform is based on exonuclease I (Exo I),
      terminal deoxynucleotidyl transferase (TdT) and methylene blue. The aptasensor
      exploits the improved sensitivity because of applications of TdT and Exo I and
      also a label-free aptamer (Apt). Furthermore, direct immobilization of
      complementary strand of aptamer (CS) instead of Apt on the surface of electrode
      prohibits Apt self-assembled monolayer aggregation and keeps the function of the
      Apt. In the absence of alpha-syn oligomer, TdT enhances lengths of Apt and CS and
      so, increases accumulation of methylene blue as redox agent on the surface of
      electrode, leading to a strong current signal. While in the presence of alpha-syn
      oligomer, Exo I digests CS on the electrode surface, resulting in less
      accumulation of methylene blue on the electrode surface and a weak current
      signal. The relative electrochemical signal of the aptasensor increased linearly
      with the logarithm of alpha-syn oligomer concentration in the range from 60 pM to
      150 nM. The detection limit was 10 pM. Furthermore, the sensor showed high
      precision and repeatability for detection of alpha-syn oligomer in serum samples.

PMID- 30278341
TI  - Boosted photoelectrochemical immunosensing of metronidazole in tablet using coral
      like g-C3N4 nanoarchitectures.
AB  - A simple, facile and sensitive photoelectrochemical (PEC) bioassay protocol for
      metronidazole (MNZ) detection in common oral medicine samples has been proposed
      under visible-light irradiation, where novel hierarchical coral-like g-C3N4
      nanoarchitectures (cg-C3N4) have been first explored as PEC sensing platform.
      Featured with the unique nanostructures (e.g., interlaced porous network
      architecture, and open boundaries), the as-formed cg-C3N4 nanoarchitectures not
      only efficiently inhibit the recombination of photogenerated electron-hole but
      also enable the immobilization of capture antibodies as well as the antibody
      antigen binding efficiency fluently, thus amplifying the photocurrent response.
      This newly constructed PEC immunoassay displays excellent performance for MNZ
      determination with high sensitivity and selectivity. Under the optimal condition,
      this bioassay protocol exhibits a linear range of 0.01-100 uM with a detection
      limit of 0.005 uM at signal to noise ratio of 3. The resulting PEC immunoassay
      has been proved to be applicable for sensing MNZ in common oral medicine samples.

PMID- 30278342
TI  - In vitro mitochondria-mediated anticancer and antiproliferative effects of Annona
      glabra leaf extract against human leukemia cells.
AB  - We investigated the in vitro mitochondria-mediated anticancer and
      antiproliferative effects of extracts of Annona glabra leafs on human leukemia
      cells. A. glabra is a tropical tree that exhibits several clinical and
      pharmacological properties in humans and is effective against cancer. We
      investigated the antiproliferative effects of an alcoholic extract of A. glabra
      on MC-1010 human monocytic leukemia cells (crl-12253) based on phytochemical
      analyses, cell viability, free radical scavenging activity, intracellular
      reactive oxygen species (ROS) levels, ATP content, mitochondrial fragmentation,
      and cell migration assays. The results indicated the presence of flavonoids,
      terpenoids, glycosides, steroids, saponins, tannins, anthraquinones, and acidic
      compounds in extracts. Leukemia cell viability was reduced up to 28% after
      incubation with the extract, while the free radical reducing power and scavenging
      activity were significantly increased. Higher concentrations of extract
      significantly inhibited leukemia cell colony formation. ROS increased up to 66%
      following incubation with extract, while the ATP content decreased up to 31%.
      Condensed, fragmented, and clumped mitochondria were observed in treated cells.
      In flow cytometric analyses, 10.7% and 22.4% of cells were apoptotic following
      incubation with 80 and 100 MUg/mL extract, respectively. Moreover, treated
      leukemia cells exhibited reduced migratory potential. Overall, the results
      suggest that leaf extracts of A. glabra may act as potential anticancer agents
      against human leukemia cells.

PMID- 30278343
TI  - Acid-triggered echogenic nanoparticles for contrast-enhanced ultrasound imaging
      and therapy of acute liver failure.
AB  - There has been increasing interest in the development of pathological stimulus
      activatable nanoplatforms with theranostic functions. Here, we report ketalized
      maltodextrin (KMD) nanoparticles which are able to deliver therapeutic and
      imaging functions to the acidic conditions simultaneously, as may be found in the
      site of inflammation. KMD was synthesized as a platform of the theranostic
      nanoparticles by conjugating acid-cleavable hydrophobic moieties to maltodextrin
      through carbonate bonds. KMD nanoparticles could undergo acid-triggered
      hydrolytic degradation to generate carbon dioxide (CO2) bubbles, amplifying the
      ultrasound signal. The potential of KMD nanoparticles as a drug carrier was
      evaluated using silymarin as a model drug. KMD nanoparticles displayed
      significantly enhanced ultrasound contrast at acidic pH and released drug
      payloads in acid-triggered manners. The translational potential of silymarin
      loaded KMD (s-KMD) nanoparticles as ultrasound contrast agents and therapeutic
      agents was thoroughly evaluated using cell culture models and mouse models of
      acetaminophen (APAP)-induced acute liver failure. s-KMD nanoparticles exhibited
      significantly enhanced ultrasound contrast in the APAP-intoxicated liver and also
      remarkably suppressed the hepatic damages by inhibiting the expression of pro
      inflammatory cytokines. These results suggest that KMD nanoparticles hold
      tremendous potential as theranostic agents for various inflammatory diseases.

PMID- 30278344
TI  - Combinatorial cassettes to systematically evaluate tissue-engineered constructs
      in recipient mice.
AB  - Ectopic bone formation in mice is the gold standard for evaluation of osteogenic
      constructs. By regular procedures, usually only 4 constructs can be accommodated
      per mouse, limiting screening power. Combinatorial cassettes (combi-cassettes)
      hold up to 19 small, uniform constructs from the time of surgery, through time in
      vivo, and subsequent evaluation. Two types of bone tissue engineering constructs
      were tested in the combi-cassettes: i) a cell-scaffold construct containing
      primary human bone marrow stromal cells with hydroxyapatite/tricalcium phosphate
      particles (hBMSCs + HA/TCP) and ii) a growth factor-scaffold construct containing
      bone morphogenetic protein 2 in a gelatin sponge (BMP2+GS). Measurements of bone
      formation by histology, bone formation by X-ray microcomputed tomography (MUCT)
      and gene expression by quantitative polymerase chain reaction (qPCR) showed that
      constructs in combi-cassettes were similar to those created by regular
      procedures. Combi-cassettes afford placement of multiple replicates of multiple
      formulations into the same animal, which enables, for the first time, rigorous
      statistical assessment of: 1) the variability for a given formulation within an
      animal (intra-animal variability), 2) differences between different tissue
      engineered formulations within the same animal and 3) the variability for a given
      formulation in different animals (inter-animal variability). Combi-cassettes
      enable a more high-throughput, systematic approach to in vivo studies of tissue
      engineering constructs.

PMID- 30278345
TI  - Bridging the gap in peripheral nerve repair with 3D printed and bioprinted
      conduits.
AB  - Over the past two decades, a number of fabrication methods, including 3D printing
      and bioprinting, have emerged as promising technologies to bioengineer nerve
      conduits that closely replicate features of the native peripheral nerve, with the
      aim of augmenting or supplanting autologous nerve grafts. 3D printing and
      bioprinting offer the added advantage of rapidly creating composite peripheral
      nerve matrices from micron-scaled units, using an assortment of synthetic,
      natural and biologic materials. In this review, we explore the evolution of
      automated 3D manufacturing technologies for the development of peripheral nerve
      conduits and discuss aspects of conduit design, based on microarchitecture,
      material selection, cell and protein inclusion, and mechanical properties, as
      they are adaptable to 3D printing. Additionally, we highlight advancements in the
      application of bio-imaging modalities toward the fabrication of patient-specific
      nerve conduits. Lastly, we outline regulatory as well as clinical challenges that
      must be surmounted for the translation of 3D printing and bioprinting technology
      to the clinic. As a whole, this review addresses topics that may situate 3D
      manufacturing at the forefront of fabrication technologies that are exploited for
      the generation of future revolutionary therapies like in situ printing of
      peripheral nerves.

PMID- 30278346
TI  - Tumor microenvironment-targeted poly-L-glutamic acid-based combination conjugate
      for enhanced triple negative breast cancer treatment.
AB  - The intrinsic characteristics of the tumor microenvironment (TME), including
      acidic pH and overexpression of hydrolytic enzymes, offer an exciting opportunity
      for the rational design of TME-drug delivery systems (DDS). We developed and
      characterized a pH-responsive biodegradable poly-L-glutamic acid (PGA)-based
      combination conjugate family with the aim of optimizing anticancer effects. We
      obtained combination conjugates bearing Doxorubicin (Dox) and aminoglutethimide
      (AGM) with two Dox loadings and two different hydrazone pH-sensitive linkers that
      promote the specific release of Dox from the polymeric backbone within the TME.
      Low Dox loading coupled with a short hydrazone linker yielded optimal effects on
      primary tumor growth, lung metastasis (~90% reduction), and toxicological profile
      in a preclinical metastatic triple-negative breast cancer (TNBC) murine model.
      The use of transcriptomic analysis helped us to identify the molecular mechanisms
      responsible for such results including a differential immunomodulation and cell
      death pathways among the conjugates. This data highlights the advantages of
      targeting the TME, the therapeutic value of polymer-based combination approaches,
      and the utility of -omics-based analysis to accelerate anticancer DDS.

PMID- 30278347
TI  - Subcortical SISCOM hyperperfusion: Should we pay more attention to it?
AB  - PURPOSE: Demonstrating cerebral blood flow changes during seizures, ictal
      interictal single photon emission computed tomography (SPECT) with co
      registration to MRI (SISCOM) reflects brain activation and its pathways of
      spread. To investigate subcortical ictal hyperperfusion patterns during focal
      seizures, we retrospectively reviewed SISCOM analysis of patients who became
      seizure-free after cortical resection. Our aim was to evaluate the relationship
      between epileptogenic zones and subcortical hyperperfusion. METHOD: 67 patients
      were identified as having SISCOM evaluation and having remained seizure-free for
      at least one year after surgical resection. SISCOM analysis was blindly reviewed
      for localization of basal ganglia (BG), thalamic (TN) and cerebellar (CH)
      hyperperfusion based on three different thresholds. Subcortical activation and
      epilepsy characteristics were then compared between patients. For a given region
      of interest and threshold, the sensitivity, specificity and positive and negative
      predictive value for correct lateralization of the epilepsy side was calculated.
      RESULTS: Depending on the threshold used, BG hyperperfusion was found in 37.3
      73.9% of patients, TN hyperperfusion in 31.3-68.1% and CH hyperperfusion in 13.5
      29%. For a threshold of 1.5, the best predictive positive value for correct
      lateralization of the epilepsy side was obtained with BG/CH coactivation (89%).
      For a threshold of 2.0 and 2.5, it was obtained with BG/TN coactivation (88%) and
      BG activation (82%), respectively. CONCLUSION: Subcortical SISCOM hyperperfusion
      could offer additional clues in terms of lateralization.

PMID- 30278348
TI  - Short-term and longer-term effects of brivaracetam on cognition and behavior in a
      naturalistic clinical setting-Preliminary data.
AB  - PURPOSE: To assess short-term and longer-term effects of brivaracetam (BRV) on
      cognition and behavior in a naturalistic clinical setting. METHODS: Analyses were
      based on 43 patients with epilepsy who had undergone a neuropsychological
      screening before adjunctive treatment with BRV and a follow-up evaluation either
      after 5 days or 25 weeks. The standard assessment focused on reaction times
      (Neurocog FX), attention and executive functions (EpiTrack), and verbal memory
      (short version of the VLMT). Self-perceived cognition and behavior was evaluated
      by an extended version of the Adverse Events Profile. In addition, health-related
      quality of life (QOLIE-10) was reassessed at the longer-term interval. RESULTS:
      Repeated measures analysis of variance revealed a significant improvement under
      BRV with regard to attention and executive functions (p = .03) without an
      interaction with the length of the observation interval. A statistical trend in
      the same direction was also seen for the reaction times (p = .07), but not for
      the unchanged verbal memory performance. Subjective measures indicated
      improvements in concentration (p = .02) and especially in comprehension (p <
      .001), and health-related quality of life (p = .002). Mood and aggression scores
      were unchanged. At the longer-term follow-up, an at least 50 percent reduction in
      seizure frequency was observed in 53% of the patients, 21% were seizure free.
      CONCLUSION: These preliminary data point to a favorable cognitive profile of BRV
      similar to its precursor levetiracetam. Objective gains in attention and
      executive functions were accompanied by self-reported improvements in
      concentration and comprehension. Future studies with larger sample sizes and
      better control conditions are needed to confirm these findings.

PMID- 30278349
TI  - Effects of natural and modified calcium-based sorbents on heavy metals of food
      waste under oxy-fuel combustion.
AB  - Performance of natural and modified calcium-based sorbents for heavy metals for
      food waste under oxy-fuel combustion in a lab-scale tubular furnace was carried
      out. The effects of furnace temperature, sorbents type, and CO2/O2 ratio on
      adsorption of heavy metals were investigated. Increasing the furnace temperature
      helped fixing Al in the bottom ash, but increased the volatilization of Zn. The
      results showed that heavy metals captured by sorbents highly depended on the
      metals types. Nature and modified CaO had excellent performance for Al capture
      while CaCO3 could not absorb Al. Neither CaCO3 or CaO could not use as sorbents
      for the Cr capture. CO2/O2 ratio highly affected the capture of Cr and Zn but had
      no influence on Al, and the decrease of CO2/O2 ratio would help capturing Cr and
      Zn. This work contributes to the heavy metals controlled by Ca-based sorbents
      during municipal solid waste oxy-fuel combustion.

PMID- 30278350
TI  - Impact of carbon to nitrogen ratio on the performance of aerobic granular reactor
      and microbial population dynamics during aerobic sludge granulation.
AB  - Carbon to nitrogen (C/N) ratio is one of the most important factor affecting
      aerobic granular sludge (AGS) growth and pollutant removal in aerobic granular
      sludge sequencing batch reactor (AGSBR). For stability of sludge granulation
      process, AGSs were domesticated in five sequence batch reactors (SBRs) with
      different C/N ratios (6, 7, 8, 9, and 10), which the ammonia nitrogen
      concentration of influent was 165 mg/L. The effects of C/N ratio on morphology
      and property of AGS were studied. The results showed that stable AGS was yielded
      with good settleability, high pollutant removal efficiency and rich microbial
      diversity when C/N ratio was 8. AGS yielded had stable structure due to higher
      protein in extracellular polymeric substances (EPS). High throughput 16S rDNA
      gene analysis revealed the microbial community diversity increased in AGS under
      the C/N ratio. The dominant microbes changed at the phylum, class and family
      three levels with the increasing operation time.

PMID- 30278351
TI  - Metabolic engineering of Clostridium tyrobutyricum for enhanced butyric acid
      production from undetoxified corncob acid hydrolysate.
AB  - Resistance to furan derivatives and phenolic compounds plays an important role in
      the use of lignocellulosic biomass for biological production of chemicals and
      fuels. This study confirmed that expression of short-chain
      dehydrogenase/reductase (SDR) from Clostridium beijerinckii NCIMB 8052
      significantly improved the tolerance of C. tyrobutyricum to furfural due to the
      enhanced activity for furfural reduction. And on this basis, co-expression of SDR
      and heat shock chaperones GroESL could simultaneously enhance the tolerance of C.
      tyrobutyricum to furan derivatives and phenolic compounds, which were the main
      inhibitors presented in dilute-acid lignocellulosic hydrolysates. Consequently,
      the recombinant strain ATCC 25755/sdr+groESL exhibited good performance in
      butyric acid production with corncob acid hydrolysate as the substrate. Batch
      fermentation in bioreactor showed that the butyrate produced by ATCC
      25755/sdr+groESL was 32.8 g/L, increased by 28.1% as compared with the wild-type
      strain. Meanwhile, the butyrate productivity increased from 0.19 g/L.h to 0.29
      g/L.h.

PMID- 30278352
TI  - Improved biobleaching of mixed hardwood pulp and process optimization using novel
      GA-ANN and GA-ANFIS hybrid statistical tools.
AB  - The process parameters for xylanase biobleaching of mixed hardwood pulp like,
      reaction time (6-35 h), pulp consistency (2.5-15%) and xylanase dose (5-35 U)
      were optimized using OFAT approach and hybrid statistical tools viz. GA-ANN and
      GA-ANFIS. The biobleaching ability of xylanase in terms of reducing sugar yield
      increased up to 28.16 mg g-1 (28.05%) than OFAT optimization (21.99 mg g-1 of
      pulp) after employing hybrid statistical tools. After TCF bleaching of xylanase
      treated pulp, we observed that lignin content reduced to 0.29% whereas it was
      still 0.41% in the untreated pulp. Moreover, the brightness level achieved up to
      70.4% in xylanase treated pulp while it was only 53.60% in the chemically treated
      pulp. The kappa number for xylanase treated, chemically treated, and xylanase
      chemical treated pulp was recorded 9.90, 7.10 and 4.70, respectively. The present
      study reports an improved eco-friendly biobleaching method using novel GA-ANN and
      GA-ANFIS hybrid statistical tools.

PMID- 30278353
TI  - Methods for tentative determination of presence of artificial nuclides in air
      using NuRMS EGS air sampler and WIMP 120 gross alpha/beta counter.
AB  - The determination of the presence of artificial radionuclides in the air is
      mainly accomplished by using gamma spectrometry analysis of filter samples. This
      work suggests very fast, reliable and efficient methods for tentative
      quantitative determination of the activity of artificial nuclides such as
      transuranic elements, strontium, yttrium, etc. in the air based only on the gross
      alpha and beta volume activity. The main aspect of these methods is to provide
      information about approximate results for the gross alpha and beta activity of
      air filters, thus it is convenient as a triage technique. Unlike gamma
      spectrometry, the methods are not qualitative but it allows the preliminary
      estimation of the presence of non-natural radionuclides. The influence of
      increment of the dust layer on self-absorption of alpha/beta particles was also
      studied. The methods are particularly suitable for screening situations where
      radionuclide identification is not necessary.

PMID- 30278355
TI  - A novel transcription factor Rwdd1 and its SUMOylation inhibit the expression of
      sqr, a key gene of mitochondrial sulfide metabolism in Urechis unicinctus.
AB  - Sulfide-quinone oxidoreductase (SQR) is a key enzyme of sulfide metabolism in
      metazoans, and responsible for oxidizing sulfide into thiosulfate and
      transmitting the generated electrons to the ubiquinone. It has been revealed that
      the sqr mRNA level increases significantly in echiuran worm Urechis unicinctus
      exposed to sulfide, and HSF1, NF1 and Sp1 have been verified to participate in
      its transcriptional regulation. In this study, we obtained 23 potential
      transcription factors interacting possibly with the proximal region (-391 to +50)
      of sqr promoter, and focused on the RWD domain-containing 1 (Rwdd1), a protein
      with the maximum number of clones in yeast one-hybrid (Y1H) screening, to
      investigate its transcriptional regulation to U. unincitus sqr. The ChIP and EMSA
      assays identified that the Rwdd1 can bind directly to the promoter (+18/+36) of
      U. unicinctus sqr. The point mutation and transient transfection experiments
      discovered that TACG was the key sequence of the DNA element bound by the Rwdd1.
      Furthermore, the U. unicinctus Rwdd1 (UuRwdd1) was identified to be a
      transcription repressor inhibiting the sqr promoter activity, and the SUMOylation
      of UuRwdd1 at the lysine of 90th enhanced its inhibitory effect on sqr
      transcription further. Western blotting found Rwdd1 responded to sulfide in
      hindguts from U. unincitus, and the protein content showed a remarkable drop in
      hindgut nuclei in the early sulfide exposure, and then increased significantly
      both in the total protein and the nuclear protein extract. We suggested that the
      Rwdd1 is a novel transcription factor, and these data improve our understanding
      of the sqr transcriptional regulation and the mitochondrial sulfide metabolism.

PMID- 30278356
TI  - CETP inhibition, statins and diabetes.
AB  - Type 2 diabetes is a causal risk factor for the development of atherosclerotic
      cardiovascular disease (ASCVD). While treatment with a statin reduces the risk of
      having an ASCVD event in all people, including those with type-2 diabetes, statin
      treatment also increases the likelihood of new onset diabetes when given to those
      with risk factors for developing diabetes. Treatment with the cholesteryl ester
      transfer protein (CETP) inhibitor, anacetrapib, reduces the risk of having a
      coronary event over and above that achieved with a statin. However, unlike
      statins, anacetrapib decreases the risk of developing diabetes. If the reduced
      risk of new-onset diabetes is confirmed in another CETP inhibitor outcome trial,
      there will be a case for considering the use of the combination of a statin plus
      a CETP inhibitor in high ASCVD-risk people who are also at increased risk of
      developing diabetes.

PMID- 30278354
TI  - Effects of ocean warming and acidification on accumulation and cellular
      responsiveness to cadmium in mussels Mytilus galloprovincialis: Importance of the
      seasonal status.
AB  - Ocean warming and acidification could represent an additional threat to marine
      organisms already coping with other anthropogenic impacts, such as chemical
      contamination in coastal areas. In this study, interactions between such multiple
      stressors and their synergistic effects in terms of accumulation, detoxification
      and biological effects of metals were investigated in the Mediterranean mussel
      Mytilus galloprovincialis. Organisms sampled during the winter period were
      exposed for 28 days to different combinations of two temperatures (10  degrees C
      and 15  degrees C), two pH/pCO2 (8.20/~400MUatm and 7.4/~3000MUatm) and two
      cadmium concentrations (0 and 20 MUg/L). Cadmium concentrations increased in
      digestive glands and gills of metal-exposed mussels and were further enhanced by
      co-exposure at higher temperature. Interactive effects of temperature and/or pH
      were observed on Cd-mediated metallothionein induction, responsiveness of
      antioxidant system and onset of oxidative damages in lipids, with tissue-specific
      effects. Immunological effects showed a generalized sensitivity of lysosomal
      membrane stability toward the investigated stressors with major effects in co
      exposed organisms. Cadmium and temperature affected phagocytosis efficiency and
      composition of haemocyte populations probably influencing the micronucleus
      frequency through varied mitotic rate. Several differences were highlighted
      between these results and those previously obtained from mussels exposed in
      summer, supporting the importance of season when addressing the tolerance of
      temperate organisms to variations of environmental factors. The elaboration of
      the whole biomarker results through weighted criteria allowed to summarize
      specific hazard indices, highlighting tissue-specific sensitivity toward multiple
      stressors and the need of improving the knowledge on interactions between
      multiple stressors.

PMID- 30278357
TI  - Increased electronegativity of high-density lipoprotein in uremia patients
      impairs its functional properties and is associated with the risk of coronary
      artery disease.
AB  - BACKGROUND AND AIMS: Uremia patients have impaired high-density lipoprotein (HDL)
      function and a high risk of coronary artery disease (CAD). Increased lipoprotein
      electronegativity can compromise lipoprotein function, but the effect of
      increased HDL electronegativity on HDL function and its association with CAD in
      uremia patient are not clear. We aimed to assess HDL electronegativity and
      various properties of HDL in uremia patients and investigate whether
      electronegative HDL is a risk factor for CAD in these individuals. METHODS: HDL
      from 60 uremia patients and 43 healthy controls was separated into 5 subfractions
      (H1H5) with increasing electronegativity by using anion-exchange chromatography.
      Lipoprotein content was analyzed by gel electrophoresis and matrix-assisted laser
      desorption/ionization time-of-flight-mass spectrometry. HDL anti-oxidant, anti
      apoptosis and cholesterol efflux activities were examined by fluorescence-based
      assays. RESULTS: The percentage of H5 HDL (H5%) was significantly higher in
      uremia patients than in controls (p < 0.001). The concentration of apolipoprotein
      (Apo) AI was lower and apolipoprotein modifications were more prevalent in uremia
      HDL subfractions than in control HDL subfractions. Carbamylation of ApoAI and
      ApoCIII was increased in more electronegative HDL subfractions from uremia
      patients. Anti-oxidant activity, anti-apoptotic activity, and cholesterol efflux
      capability were reduced in HDL subfractions from uremia patients when compared
      with control HDL subfractions. Multiple logistic regression analysis showed that
      H5% was associated with CAD risk in uremia patients. CONCLUSIONS: In HDL of
      uremia patients, increased electronegativity is accompanied by compositional
      changes and impaired function. Our findings indicate that increased H5% is
      associated with increased CAD risk in uremia patients.

PMID- 30278358
TI  - Cold shock Y-box binding protein-1 acetylation status in monocytes is associated
      with systemic inflammation and vascular damage.
AB  - BACKGROUND AND AIMS: In dialysis patients, vascular morbidities are highly
      prevalent and linked to leukocyte extravasation, especially of polarized
      monocytes. Experimental data demonstrate that phenotypic changes in monocytes
      require Y-box binding protein-1 (YB-1) upregulation. METHODS: We determined YB-1
      expression in circulating and vessel-invading monocytes from healthy controls and
      dialysis patients to correlate results with intima plaque formation and systemic
      inflammation. RESULTS: Compared to healthy subjects, dialysis patients have fewer
      classical and more intermediate and non-classical monocytes. Post-translationally
      modified YB-1 (lysine 301/304 acetylation) is detected at high levels in the
      nucleus of adherent and invading CD14+CD68+ monocytes from umbilical cord and
      atherosclerosis-prone vessels. The content of non-acetylated YB-1 is
      significantly decreased (p < 0.001), whereas acetylated YB-1 is correspondingly
      increased (p < 0.001) throughout all monocyte subpopulations, such that the
      overall content remains unchanged. CONCLUSIONS: In dialysis patients the YB-1
      acetylation status is higher with prevailing diabetes and intima plaque
      formation. Pro-inflammatory mediators TNFalpha, IL-6, uPAR, CCL2, M-CSF,
      progranulin, ANP, and midkine, as well as anti-inflammatory IL-10 are
      significantly increased in dialysis patients, emphasizing a systemic inflammatory
      milieu. Strong positive correlations of monocytic YB-1 content are seen with ANP,
      IP-10, IL-6, and IL-10 serum levels. This is the first study demonstrating an
      association of cold shock protein YB-1 expression with inflammation in
      hemodialysis patients.

PMID- 30278359
TI  - Gender differences in the association of syndecan-4 with myocardial infarction:
      The population-based Tromso Study.
AB  - BACKGROUND AND AIMS: Cardiovascular disease is a common cause of morbidity and
      mortality, with gender differences in pathophysiology. The endothelial glycocalyx
      maintains vascular integrity, and glycocalyx shedding reflects endothelial
      dysfunction and early atherosclerosis. Syndecan-1 and -4 are components of the
      glycocalyx, and increased serum levels indicate glycocalyx damage. We
      hypothesised that increased serum syndecan-1 and -4 were independently associated
      with myocardial infarction (MI), ischaemic stroke and all-cause mortality in men
      and women from a general population. METHODS: Using a case-cohort design, we
      included 1495 participants from the Tromso Study 2001-02. Syndecan-1 and -4 were
      measured in serum. Baseline variables also included age, gender, cardiovascular
      risk factors and urinary albumin-creatinine ratio (ACR). Hazard ratios were
      assessed using multivariable Cox regression models. RESULTS: Between baseline in
      2001-02 and December 2007 fatal or non-fatal MI was experienced by 328 and
      ischaemic stroke by 191 subjects, and 423 participants died. Syndecan-4 was
      independently associated with MI (hazard ratio per 10 ng/mL increase 1.32; 95%
      confidence interval 1.06-1.63), but not ischaemic stroke and mortality, and the
      associations were unchanged by adjustment for urinary ACR. Interaction between
      syndecan-4 and sex was borderline significant, and in gender-specific analysis,
      syndecan-4 was associated with MI in women only. Syndecan-1 was not associated
      with any endpoint. CONCLUSIONS: Syndecan-4 was associated with incident MI, and
      the association was stronger in women than in men. This suggests a link between
      endothelial glycocalyx shedding and coronary heart disease in women. Use of
      syndecan-4 as a risk marker in clinical setting needs further investigation.

PMID- 30278360
TI  - Nucleation and growth of pores in 1,2-Dimyristoyl-sn-glycero-3-phosphocholine
      (DMPC) / cholesterol bilayer by antimicrobial peptides melittin, its mutants and
      cecropin P1.
AB  - Antimicrobial peptides are one of the most promising alternatives to antibiotics
      for targeting pathogens without developing resistance. In this study, pore
      formation in 1,2-Dimyristoyl-snglycero-3-phosphocholine (DMPC) / cholesterol
      liposome induced by native melittin, its two mutant variants (G1I and I17 K), and
      cecropin P1 was investigated by monitoring the dynamics of fluorescence dye
      leakage. A critical peptide concentration was required for dye leakage with the
      rate of leakage being dependent on peptide concentration above a critical value.
      A lag time was required for dye leakage for low peptide concentrations that are
      above the critical value, which decreased at higher peptide concentrations
      eventually approaching zero. Lag time was found to be in the order I17 K mutant
      with lower hydrophobicity and higher net charge > G1I with higher hydrophobicity
      > melittin > cecropin P1. Cecropin P1 exhibited the highest rate of dye leakage
      followed by melittin, G1I, and I17 K. Size distribution and transmission electron
      microscopy (TEM) of liposomes exposed to peptides of different concentrations
      indicated pore formation with accompanied stretching of liposomes at low peptide
      concentrations for both melittin and cecropin P1. At much higher concentrations,
      however, size distribution indicated three peaks for both peptides. In both
      cases, TEM images show that the middle and small peaks are shown to be due to
      stretched liposome and broken stretched liposome respectively. For melittin, the
      large peak is due to peptide aggregates as well as aggregates of liposome. For
      cecropin P1, however, the large peak indicates cecropin P1 aggregates with
      solubilized lipids thus suggesting carpet mechanism.

PMID- 30278361
TI  - Investigation of the structural conformation and surface interaction of desired
      chimeric hydrophobin: Interface simulation via molecular dynamics.
AB  - Hydrophobins are small amphiphilic fungal proteins that are highly surface-active
      and are used in various industrial applications such as dispersion,
      immobilization, and antifouling. At hydrophobic-hydrophilic interfaces,
      hydrophobins tend to self-assemble as rodlets or monolayers, depending on whether
      they are class I or II. Several studies have determined the three-dimensional
      structure and investigated the self-assembly formation mechanism of the class I
      EAS from Neurospora crassa and the class II HFBII from Trichoderma reesei.
      Although some studies have examined the performance of chimeric hydrophobins,
      they have not been investigated at the atomic scale. Here, we designed chimeric
      hydrophobins by grafting the L1 loop of Vmh2 and the L3 loop of EAS onto the
      class II hydrophobin HFBII by homology modeling and performed vacuum-water
      interface molecular simulations to determine their structural behaviors. We found
      that the chimeric hydrophobin grafted with the L3 of EAS became unstable under
      standard conditions, whereas that grafted with the L1 of Vmh2 became unstable in
      the presence of calcium ions. Moreover, when both the EAS L3 and Vmh2 L1 were
      grafted together, the structure became disordered and lost its amphiphilic
      characteristics in standard conditions. In the presence of calcium, however, its
      structural stability was restored. However, an additional external perturbation
      is required to trigger the conformational transition. Although our chimeric
      hydrophobin models were designed through homology modeling, our results provide
      detailed information regarding hydrophobin self-assembly and their surface
      interactive behavior that may serve as a template for designing hydrophobins for
      future industrial applications.

PMID- 30278362
TI  - Extracellular electron transfer of Bacillus cereus biofilm and its effect on the
      corrosion behaviour of 316L stainless steel.
AB  - Here, a heterogeneous Bacillus cereus (B. cereus) biofilm on the surface of 316 L
      stainless steel (SS) was observed. With electrochemical measurement and surface
      analysis, it was found that B. cereus biofilm could inhibit SS pitting corrosion,
      attributing to the blocking effect of bacterial biofilm on extracellular electron
      transfer (EET). Differential pulse voltammetry (DPV) and cyclic voltammetry (CV)
      results also showed that B. cereus biofilm clearly impeded the EET. The proposed
      mechanism for the decreased corrosion rates of SS involves the interactions of
      extracellular polymeric substance (EPS) with SS and biofilm formation blocking
      electron transfer, preventing the passive layer from destroying. After biofilm
      formation following initial attachment of cells and EPS, electron transfer
      between SS and the cathodic depolarizer (oxygen) was hindered.

PMID- 30278363
TI  - Human health risks due to exposure to inorganic and organic chemicals from
      textiles: A review.
AB  - It is well known that a number of substances used in the textile industry can
      mean not only environmental, but also health problems. The scientific literature
      regarding potential adverse health effects of chemical substances in that
      industry is mainly related with human exposure during textile production.
      However, information about exposure of consumers is much more limited. Although
      most research on the health effects of chemicals in textiles concern allergic
      skin reactions, contact allergy is not the only potential human health problem.
      In this paper, we have reviewed the current scientific information regarding
      human exposure to chemicals through skin-contact clothes. The review has been
      focused mainly on those chemicals whose probabilities of being detected in
      clothes were rather higher. Thus, we have revised the presence of flame
      retardants, trace elements, aromatic amines, quinoline, bisphenols,
      benzothiazoles/benzotriazoles, phthalates, formaldehyde, and also metal
      nanoparticles. Human dermal exposure to potentially toxic chemicals through skin
      contact textiles/clothes shows a non-negligible presence in some textiles, which
      might lead to potential systemic risks. Under specific circumstances of exposure,
      the presence of some chemicals might mean non-assumable cancer risks for the
      consumers.

PMID- 30278365
TI  - Significant effects of exposure to relatively low level ozone on daily mortality
      in 17 cities from three Eastern Asian Countries.
AB  - BACKGROUND: Studies have examined the variation in mortality risk associated with
      ambient ozone. We conducted an international cooperation study for investigating
      the non-linear ozone-mortality association accounting for lag effect and for
      examining the ozone level with significant health effect. METHODS: Daily counts
      of total non-accidental death and ambient air pollutant concentration were
      obtained in 17 cities from 3 Eastern Asian countries or regions (Taiwan, Korea,
      and Japan). The total study period was from 1979 to 2010 and differed by city
      based on data availability. The ozone-mortality association in each city was
      estimated by running a time-series quasi-Poisson regression model, allowing for
      overdispersion. The city-specific estimates were then pooled by country by using
      multivariate random effects meta-analysis. RESULTS: The non-linear ozone exposure
      mortality response curves were generated in 17 cities from Taiwan, Korea, and
      Japan. The association curves in the three countries all showed increased
      mortality with elevated ozone, and the significant mortality effects of ozone
      exposure were observed at level higher than 40, 50, and 40 ppb for Taiwan, Korea,
      and Japan, respectively. These associations are unaffected by co-pollutant of
      particulate matter in Taiwan and Japan. But the potential confounding effect of
      co-pollutant could not be ignorable in Korea. CONCLUSIONS: Our study provides
      evidence that exposure to a relative low level of ambient ozone is associated
      with an increased risk of mortality. Our results emphasize the continual need to
      examine the existing standard by documenting potential human adverse effects.

PMID- 30278364
TI  - Self-reported myocardial infarction and fatal coronary heart disease among oil
      spill workers and community members 5 years after Deepwater Horizon.
AB  - BACKGROUND: Chemical, physical and psychological stressors due to the 2010
      Deepwater Horizon oil spill may impact coronary heart disease (CHD) among exposed
      populations. Using longitudinal information from two interviews in the Gulf Long
      Term Follow-up (GuLF) STUDY, we assessed CHD among oil spill workers and
      community members. OBJECTIVE: To assess the associations between duration of oil
      spill clean-up work, residential proximity to the oil spill, and incidence of
      self-reported myocardial infarction or fatal CHD. METHODS: Among respondents with
      two GuLF STUDY interviews (n = 21,256), there were 395 first incident heart
      disease events (self-reported myocardial infarction or fatal CHD) across 5 years.
      We estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for
      associations with duration of oil spill clean-up work and residential proximity
      to the oil spill. To assess potential impacts of non-response, we compared
      covariate distributions for those who did (n = 21,256) and did not (n = 10,353)
      complete the second interview and used inverse probability (IP) of censoring
      weights to correct for potential non-response bias. RESULTS: Living in proximity
      to the oil spill (vs. living further away) was associated with heart disease,
      with [HR(95%CI) = 1.30(1.01-1.67)] and without [1.29(1.00-1.65)] censoring
      weights. For work duration, hazard of heart disease appeared to be higher for
      those who worked > 180 days (vs. 1-30 days), with and without censoring weights
      [1.43(0.91-2.25) and 1.36(0.88-2.11), respectively]. Associations persisted
      throughout the 5-year follow-up. CONCLUSIONS: Residential proximity to the spill
      and duration of clean-up work were associated with a suggested 29-43% higher
      hazard of heart disease events. Associations were robust to censoring.

PMID- 30278366
TI  - Green synthesis of CuO nanomaterials and their proficient use for organic waste
      removal and antimicrobial application.
AB  - Copper oxide (CuO) nanomaterials (NMs) of different size and morphology were
      synthesized by Chemical precipitation, Microwave irradiation and Hydrothermal
      method and characterized by TEM, BET, FTIR, XRD and EDX analysis. As synthesized
      CuO NMs were utilized for elimination of harmful dyes viz. Direct Red 81 (DR-81)
      and Coomassie Brilliant blue R-250 (BBR-250) and pathogenic bacteria
      (Staphylococcus aureus). Owing to their morphology, smaller size and relatively
      high surface area (40.320 m2 g-1), CuO NMs prepared by chemical precipitation
      method were observed to show better adsorption capacity for both the dyes (68.70
      (DR-81) and 73.04 (BBR-250) mg g-1). The influence of different experimental
      conditions was studied by the methodical assessments of various parameters such
      as pH, adsorbent dose, concentration and contact time. Moreover, different
      adsorption isotherms and pseudo-second order kinetic model were applied to
      understand the adsorption mechanism. Langmuir model was found to be best fit thus
      confirming the monolayer adsorption process. To ensure the practical utility of
      CuO NMs for organic waste removal, the adsorption studies were performed in the
      presence of different inorganic ions and real water samples. In addition,
      recovery of the dye and NMs were also carried out effectively by simple method,
      thus avoiding the secondary pollution. CuO NMs were observed to exhibit
      significant antibacterial activity against the human pathogenic bacteria. These
      studies demonstrated that synthesized CuO NMs showed good adsorption efficiency
      for the removal of harmful dyes and antimicrobial activity against the pathogenic
      bacteria, which vary as a function of size and surface area.

PMID- 30278367
TI  - The molybdenum storage protein - A bionanolab for creating experimentally
      alterable polyoxomolybdate clusters.

PMID- 30278368
TI  - Is the occiput-wall distance valid and reliable to determine the presence of
      thoracic hyperkyphosis?
AB  - BACKGROUND: Hyperkyphosis may be frequently found nowadays due to the change in
      current lifestyles of sustained flexion postures and age-related system decline.
      The occiput-wall distance (OWD) is a practical measure that is commonly used to
      screen and monitor thoracic hyperkyphosis in epidemiologic studies. However,
      there was no clear evidence to support the clinical utility of the tool as
      compared to the data from direct standard measures. OBJECTIVES: To investigate
      psychometric properties-including validity, reliability, and appropriate cut-off
      point-of the OWD to determine the presence of thoracic hyperkyphosis, as compared
      to a standard Cobb's method. DESIGN: Observational study. METHODS: This study was
      conducted in ninety-nine participants, aged 10 years and above who had different
      degrees of thoracic hyperkyphosis from several communities. All participants were
      assessed for their severity of thoracic hyperkyphosis using the OWD, and 14
      participants were involved in a reliability study. Within 7 days later, all
      participants were at a hospital to complete a radiographic examination. RESULTS:
      Outcomes from OWD had good concurrent validity with the Cobb angles (r = 0.683, P
      < 0.001) and excellent rater reliability when assessed by well-trained health
      professionals (ICCs > 0.9, P < 0.001). The OWD of at least 6.5 cm had the best
      diagnostic properties to determine the presence of thoracic hyperkyphosis
      (sensitivity = 71.4%, specificity = 76.6%, and area under the curve = 0.846).
      CONCLUSION: The findings support validity and reliability of OWD, and offer a
      clear cut-off point to determine the presence of thoracic hyperkyphosis for
      clinical utility in various settings.

PMID- 30278370
TI  - The effect of sulfur dioxide addition at crush on the fungal and bacterial
      communities and the sensory attributes of Pinot gris wines.
AB  - Modern day winemaking often involves the addition of sulfur dioxide (SO2) at
      crush to act as both an antioxidant and an antimicrobial agent. While the effects
      of SO2 on microbial communities and particularly on spoilage microorganisms has
      been well-studied, the advent of culture-independent molecular technologies, such
      as Illumina sequencing, allows the subject to be re-visited in a new context.
      High-throughput amplicon sequencing allows for a more thorough evaluation of
      microbial communities, as thousands of microbial sequences per sample can be
      identified and even rare microorganisms can be studied. This research
      investigated whether the addition of different levels of SO2 at crush (0, 20, or
      40 mg/L) would affect the composition of fungal and bacterial communities, as
      well as the sensory attributes of the resulting wines. Samples were taken from
      uninoculated fermentations of Pinot gris and analyzed via high-throughput
      amplicon sequencing using the Illumina MiSeq platform. Yeast relative abundance
      and overall fungal community composition differed among the SO2 additions.
      Notably, a Hanseniaspora yeast appeared in all treatments and persisted until the
      end of alcoholic fermentation, although its relative abundance was significantly
      higher in the fermentations to which low or no SO2 had been added. Two key wine
      sensory attributes (citrus aroma and pome fruit flavor) differed among the SO2
      treatments. This research provides an in-depth look into the fungal and bacterial
      communities during alcoholic fermentation and gives a better understanding of the
      microbial community response to SO2 additions during the crush period.

PMID- 30278369
TI  - The presentation, management and outcome of inflammatory breast cancer cases in
      the UK: Data from a multi-centre retrospective review.
AB  - OBJECTIVES: Inflammatory Breast cancer (IBC) is a rare but aggressive form of
      breast cancer. Its incidence and behaviour in the UK is poorly characterised. We
      collected retrospective data from hospitals in the UK and Ireland to describe the
      presentation, pathology, treatment and clinical course of IBC in the UK.
      MATERIALS AND METHODS: Patients with IBC diagnosed between 1997-2014 at fourteen
      UK and Irish hospitals were identified from local breast unit databases. Patient
      characteristics, tumour pathology and stage, and details of surgical, systemic
      and radiotherapy treatment and follow-up data were collected from electronic
      patient records and medical notes. RESULT: This retrospective review identified
      445 patients with IBC accounting for 0.4-1.8% of invasive breast cancer cases.
      Median follow-up was 4.2 years. 53.2% of tumours were grade 3, 56.2% were
      oestrogen receptor positive, 31.3% were HER2 positive and 25.1% were triple
      negative. 20.7% of patients had distant metastases at presentation. Despite
      trimodality treatment in 86.4%, 40.1% of stage III patients developed distant
      metastases. Five-year overall survival (OS) was 61.0% for stage III and 21.4% for
      stage IV patients. CONCLUSIONS: This is the largest series of UK IBC patients
      reported to date. It indicates a lower incidence than in American series, but
      confirms that IBC has a high risk of recurrence with poor survival despite
      contemporary multi-modality therapy. A national strategy is required to
      facilitate translational research into this aggressive disease.

PMID- 30278371
TI  - Is impaired information processing speed a matter of structural or functional
      damage in MS?
AB  - OBJECTIVE: Cognitive deficits, especially those of information processing speed
      (IPS), are common in multiple sclerosis (MS), however, the underlying
      neurobiological mechanisms remain poorly understood. In this study, we examined
      structural and functional brain changes separately, but also in an integrative
      manner, in relation to IPS performance. METHODS: IPS was measured using the
      symbol digit modalities test (SDMT) in 330 MS patients and 96 controls. Patients
      with IPS impairment (IPS-I, z-score < -1.5) were compared to patients with
      preserved IPS performance (IPS-P) on volumetric measures, white matter integrity
      loss (using diffusion tensor imaging) and the severity of functional connectivity
      changes (using resting-state fMRI). Significant predictors of IPS performance
      were used to create groups of mild or severe structural and/or functional damage
      to determine the relative effect of structural and/or functional changes on IPS.
      RESULTS: IPS-I patients, compared to IPS-P patients, showed lower deep gray
      matter volume and less WM integrity, but stronger increases in functional
      connectivity. Patients with predominantly structural damage had worse IPS (z
      score = -1.49) than patients with predominantly functional changes (z-score = 
      0.84), although both structural and functional measures remained significant in a
      regression model. Patients with severe structural and functional changes had
      worst IPS (z-score = -1.95). CONCLUSION: The level of structural damage explains
      IPS performance better than functional changes. After integrating functional and
      structural changes, however, we were able to detect more subtle and stepwise
      decline in IPS. In subgroups with a similar degree of structural damage, more
      severe functional changes resulted in worse IPS scores than those with only mild
      functional changes.

PMID- 30278372
TI  - Voxel-wise deviations from healthy aging for the detection of region-specific
      atrophy.
AB  - The identification of pathological atrophy in MRI scans requires specialized
      training, which is scarce outside dedicated centers. We sought to investigate the
      clinical usefulness of computer-generated representations of local grey matter
      (GM) loss or increased volume of cerebral fluids (CSF) as normalized deviations
      (z-scores) from healthy aging to either aid human visual readings or directly
      detect pathological atrophy. Two experienced neuroradiologists rated atrophy in
      30 patients with Alzheimer's disease (AD), 30 patients with frontotemporal
      dementia (FTD), 30 with dementia due to Lewy-body disease (LBD) and 30 healthy
      controls (HC) on a three-point scale in 10 anatomical regions as reference gold
      standard. Seven raters, varying in their experience with MRI diagnostics rated
      all cases on the same scale once with and once without computer-generated volume
      deviation maps that were overlaid on anatomical slices. In addition, we
      investigated the predictive value of the computer generated deviation maps on
      their own for the detection of atrophy as identified by the gold standard raters.
      Inter and intra-rater agreements of the two gold standard raters were substantial
      (Cohen's kappa kappa > 0.62). The intra-rater agreement of the other raters
      ranged from fair (kappa = 0.37) to substantial (kappa = 0.72) and improved on
      average by 0.13 (0.57 < kappa < 0.87) when volume deviation maps were displayed.
      The seven other raters showed good agreement with the gold standard in regions
      including the hippocampus but agreement was substantially lower in e.g. the
      parietal cortex and did not improve with the display of atrophy scores. Rating
      speed increased over the course of the study and irrespective of the presentation
      of voxel-wise deviations. Automatically detected large deviations of local volume
      were consistently associated with gold standard atrophy reading as shown by an
      area under the receiver operator characteristic of up to 0.95 for the hippocampus
      region. When applying these test characteristics to prevalences typically found
      in a memory clinic, we observed a positive or negative predictive value close to
      or above 0.9 in the hippocampus for almost all of the expected cases. The volume
      deviation maps derived from CSF volume increase were generally better in
      detecting atrophy. Our study demonstrates an agreement of visual ratings among
      non-experts not further increased by displaying, region-specific deviations of
      volume. The high predictive value of computer generated local deviations
      independent from human interaction and the consistent advantages of CSF-over GM
      based estimations should be considered in the development of diagnostic tools and
      indicate clinical utility well beyond aiding visual assessments.

PMID- 30278374
TI  - Rapid and efficient differentiation of functional motor neurons from human iPSC
      for neural injury modelling.
AB  - Primary rodent neurons and immortalised cell lines have overwhelmingly been used
      for in vitro studies of traumatic injury to peripheral and central neurons, but
      have some limitations of physiological accuracy. Motor neurons (MN) derived from
      human induced pluripotent stem cells (iPSCs) enable the generation of cell models
      with features relevant to human physiology. To facilitate this, it is desirable
      that MN protocols both rapidly and efficiently differentiate human iPSCs into
      electrophysiologically active MNs. In this study, we present a simple, rapid
      protocol for differentiation of human iPSCs into functional spinal (lower) MNs,
      involving only adherent culture and use of small molecules for directed
      differentiation, with the ultimate aim of rapid production of
      electrophysiologically functional cells for short-term neural injury experiments.
      We show successful differentiation in two unrelated iPSC lines, by quantifying
      neural-specific marker expression, and by evaluating cell functionality at
      different maturation stages by calcium imaging and patch clamping. Differentiated
      neurons were shown to be electrophysiologically altered by uniaxial mechanical
      deformation. Spontaneous network activity decreased with applied stretch,
      indicating aberrant network connectivity. These results demonstrate the
      feasibility of this rapid, simple protocol for differentiating iPSC-derived MNs,
      suitable for in vitro neural injury studies focussing on electrophysiological
      alterations caused by mechanical deformation or trauma.

PMID- 30278373
TI  - Structural covariance networks relate to the severity of epilepsy with focal
      onset seizures.
AB  - PURPOSE: The brains of patients with epilepsy may exhibit various morphological
      abnormalities, which are often not directly visible on structural MR images, as
      they may be focally subtle or related to a more large-scale inconspicuous
      disorganization of brain structures. To explore the relation between structural
      brain organization and epilepsy characteristics, including severity and cognitive
      co-morbidity, we determined structural covariance networks (SCNs). SCNs represent
      interregional correlations of morphologic measures, for instance in terms of
      cortical thickness, between various large-scale distributed brain regions.
      METHODS: Thirty-eight patients with focal seizures of all subtypes and 21 healthy
      controls underwent structural MRI, neurological, and IQ assessment. Cortical
      thickness was derived from the structural MRIs using FreeSurfer. Subsequently,
      SCNs were constructed on a group-level based on correlations of the cortical
      thicknesses between various brain regions. Individual SCNs for the epilepsy
      patients were extracted by adding the respective patient to the control group
      prior to the SCN construction (i.e. add-one-patient approach). Calculated network
      measures, i.e. path length, clustering coefficient and betweenness centrality
      were correlated with characteristics related to the severity of epilepsy,
      including seizure history and age at onset of epilepsy, and cognitive
      performance. RESULTS: Stronger clustering in the individual SCN was associated
      with a higher number of focal to bilateral tonic-clonic seizures during life
      time, a younger age at onset, and lower cognitive performance. The path length of
      the individual SCN was not related to the severity of epilepsy or cognitive
      performance. Higher betweenness centrality of the left cuneus and lower
      betweenness centrality of the right rostral middle frontal gyrus were associated
      with increased drug load and younger age at onset, respectively. CONCLUSIONS:
      These results indicate that the correlations between interregional variations of
      cortical thickness reflect disease characteristics or responses to the disease
      and deficits in patients with epilepsy with focal seizures.

PMID- 30278375
TI  - Viral-free generation and characterization of a human induced pluripotent stem
      cell line from dermal fibroblasts.
AB  - Peripheral dermal fibroblasts (DF) from a healthy 56 year old female were
      obtained from the Centre for Healthy Brain Ageing (CHeBA) Biobank, University of
      New South Wales, under the material transfer agreement with the University of
      Wollongong. DFs were reprogrammed via mRNA-delivered transcription factors into
      induced pluripotent stem cells (iPSCs). The generated iPSCs were confirmed to be
      pluripotent, capable of three germ layer differentiation and are thus a useful
      resource for creating iPSC-derived healthy human cells of any lineage. Resource
      table.

PMID- 30278376
TI  - Construction of a GLI3 compound heterozygous knockout human embryonic stem cell
      line WAe001-A-20 by CRISPR/Cas9 editing.
AB  - The human GLI3 protein has a dual function as a transcriptional activator or
      repressor of hedgehog signaling, depending on the proteolytic processing forms of
      GLI3. In this study, we established a compound heterozygous GLI3 mutant human
      embryonic stem cell line (WAe001-A-20) through CRISPR/Cas9 editing. The WAe001-A
      20 cells carried two deletions on two different alleles of exon 2 of GLI3,
      respectively, which resulted in a frame shift and early termination in the
      translation of GLI3. Moreover, WAe001-A-20 maintains a normal karyotype, parental
      cell morphology, pluripotent phenotype and the ability to differentiate into
      three germ layers. Resource table.

PMID- 30278377
TI  - A comprehensive analysis of gestational trophoblastic neoplasia trials posted at
      online clinical trial registries.
AB  - OBJECTIVE: We conducted a comprehensive analysis of gestational trophoblastic
      neoplasia (GTN) trials posted at online registries and aimed to provide useful
      information for future GTN trial designs. STUDY DESIGN: We searched
      ClinicalTrials.gov, EU Clinical Trials Register, WHO International Clinical
      Trials Registry Portal (ICTRP) Search Portal, Australian New Zealand Clinical
      Trial Registry, ISRCTN Register, and Chinese Clinical Trial Register for all the
      clinical trials reporting GTN treatments. The general information of each trial
      was extracted. RESULTS: Twenty trials meeting the inclusion criteria were
      included in the final analysis. In total, 6 trials were phase II trials, 2 were
      phase II/III trials, 7 were phase III trials, and 1 was a phase IV trial; and the
      phase type of 4 trials were not reported. The conditions included low-risk GTN (n
      = 15), high-risk GTN (n = 2), and mixed GTN (n = 3). Randomization was performed
      in 15 trials, and the remaining 5 trials were single-arm trials. The median
      enrollment size for randomized clinical trials (RCTs) and single-arm trials was
      80 and 38, respectively. Among the RCTs, parallel assignment was used in 12
      trials, crossover assignment was used in 1, and the intervention models of 2 were
      not reported. For masking, 15 trials were open-label, 2 were single-blinded, 2
      were double-blinded, and the masking status of 1 was not reported. Ovarian
      functions and pregnancy outcome after chemotherapy were evaluated in only 2
      trials. Regarding sponsorship, 2 trials had industry sponsorship. CONCLUSION:
      Conducting RCTs for GTN is challenging, and international collaboration and
      smarter clinical trial designs are required for future GTN trials.

PMID- 30278379
TI  - A study on collaborative telepsychiatric consultations to outpatients of district
      hospitals of Karnataka, India.
AB  - INTRODUCTION: The Indian National Mental Health Survey (NMHS) of 2015-2016 has
      estimated 13.7% lifetime and 10.6% point prevalence for mental illnesses. It has
      identified that the treatment gap for mental illnesses ranges between 70% and
      92%. Tele-Psychiatric consultations could be an alternative and innovative
      approach to bridge this gap in low resource settings. AIMS: To study the
      sociodemographic and clinical profiles of patients who have received
      collaborative Tele-Psychiatric consultations across district hospitals in
      Karnataka, India. METHODOLOGY: We performed a retrospective review of case files
      of patients who have received collaborative Tele-Psychiatric consultations from
      January 2013 to June 2017 through video-conferencing. A total of 139
      consultations were provided to patients in the state of Karnataka. RESULTS: The
      mean age of the sample is 31 (+/-15.5) years. 61.8% were male and 79.8% were aged
      more than 18 years. In total, 25.9% of them had schizophrenia and other psychotic
      disorders, 14.4% had mental retardation, 13.7% had a mood disorder and 14.4% had
      a substance use disorder. 67.6% of patients had been advised pharmacotherapy,
      7.9% had been advised rehabilitation along with pharmacotherapy and 24.4% were
      advised further evaluation of illness and inpatient care at a higher centre.
      CONCLUSION: Collaborative tele-psychiatric consultations to district hospitals
      from an academic tertiary care hospital can be feasible and are likely to benefit
      patients from rural areas. There is a need for more studies to elucidate their
      acceptability by patients, caregivers and professionals.

PMID- 30278378
TI  - A phase 1b study of afatinib in combination with standard-dose cetuximab in
      patients with advanced solid tumours.
AB  - This phase 1b, open-label trial assessed the combination of afatinib, an ErbB
      family blocker, with cetuximab, an epidermal growth factor receptor (EGFR)
      monoclonal antibody, in heavily pretreated patients with unselected/EGFR wild
      type, advanced solid tumours. In Part A, the maximum tolerated dose (MTD) of
      afatinib + cetuximab was evaluated using a 3 + 3 dose-escalation design; the
      starting dose was afatinib 30 mg/day plus cetuximab 250 mg/m2/week (after
      cetuximab 400 mg/m2 loading dose), escalating to afatinib 40 mg/day. Part B
      further evaluated safety and tolerability at the MTD and preliminary anti-tumour
      activity in three patient cohorts with squamous non-small cell lung cancer
      (NSCLC), head and neck squamous cell carcinoma (HNSCC) and other solid tumours.
      Nine patients were treated in Part A; the MTD and recommended dose was determined
      as afatinib 40 mg/day plus cetuximab 250 mg/m2/week. In Part B, 49 patients were
      treated at the recommended dose (12 with squamous NSCLC, 15 with HNSCC and 22
      with other tumours). The most common treatment-related adverse events (AEs)
      across all 58 patients were diarrhoea (63.8%) and acneiform dermatitis (43.1%).
      Overall, the best confirmed response was stable disease (SD; 53.4%); mean
      duration of disease control was 4.5 months; median progression-free survival was
      2.6 months. In Part B, 55.1% of patients had SD (squamous NSCLC, 75.0%; HNSCC,
      66.7%; other tumours; 36.4%). In conclusion, the recommended phase 2 dose was
      determined as afatinib 40 mg/day plus cetuximab 250 mg/m2/week. AEs were
      predictable and manageable, and anti-tumour activity was observed in some
      patients, particularly in those with squamous NSCLC and HNSCC. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02020577.

PMID- 30278380
TI  - Understanding the potential for selective natural organic matter removal by ion
      exchange.
AB  - Dissolved organic carbon (DOC) removal from a river water source was investigated
      using ion exchange (IEX), coagulation and membrane filtration. This research
      linked the variable charge characteristics of the organic compounds present in
      the source water with removal by IEX and coagulation. The raw water charge
      density fluctuated considerably (between 5.4 and 10.7 meq mgDOC-1) and controlled
      removal of the charge loading. Importantly, charge density was not correlated
      with the organic carbon concentration. The combined IEX and coagulation process
      reduced the specific DBP-FP (sDBP-FP) of the final water, with values as low as
      18 MUg mgDOC-1 for both haloacetic acids and trihalomethanes. IEX removed a
      particular fraction of NOM that 1) enhanced coagulation efficiency, providing
      increased removal of overall DOC; and 2) enabled coagulation to subsequently
      remove higher levels of specific components of NOM that have a high DBP-FP. The
      component of NOM removed by IEX that had a positive impact on coagulation was
      identified to be charged low molecular weight organic compounds of all
      hydrophobicity levels, resulting in a reduced specific DBP-FP compared to
      coagulation alone.

PMID- 30278381
TI  - Effects of Escherichia coli and phosphate on the transport of titanium dioxide
      nanoparticles in heterogeneous porous media.
AB  - Transport behaviors of titanium dioxide nanoparticles (nTiO2) were examined in
      the individual- and co-presence Escherichia (E.) coli and phosphate in
      heterogeneous sand (uncoated and iron oxyhydroxide-coated sand) columns. The
      results showed that for the individual presence of phosphate, the degree of nTiO2
      deposition was less in uncoated than in iron oxide-coated sands. In contrast, an
      opposite trend that greater deposition of nTiO2 in uncoated than in coated sands
      occurred in the individual presence of E. coli. These observations are due to the
      phosphate adsorption changing the charge of NPs and iron oxyhydroxide-coated
      sand, or the preferential adhesion of bacterial to coated sand. In the copresence
      of E. coli and phosphate, interestingly, the phosphate level plays an important
      role in influencing nTiO2 transport. At a high phosphate concentration (>1.0 mM),
      the deposition of nTiO2 with the individual presence of E. coli was stronger than
      nTiO2 in the copresence of both E. coli and phosphate, regardless of sand type.
      The potential mechanism was that phosphate adsorption led to the formation of
      more negatively charged NPs-bacteria complexes that have higher mobility in sand
      columns. At a low phosphate level (<=0.1 mM), a similar observation occurred in
      uncoated sand. Nevertheless, the deposition of nTiO2 with copresence of E. coli
      and phosphate was greater than nTiO2 with E. coli in oxyhydroxide-coated sand. It
      was attributed to the formation of large NPs-bacteria-phosphate clusters (less
      mobile) and the preferential adhesion of E. coli cells to iron oxyhydroxide
      coating simultaneously. Taken together, our findings provide crucial knowledge
      for better understanding the fate, transport, and potential risks of engineered
      nanoparticles in complicated environmental settings where bacteria and phosphate
      are ubiquitous.

PMID- 30278382
TI  - Inhibitory effects of ammonia on syntrophic propionate oxidation in anaerobic
      digester sludge.
AB  - Syntrophic propionate oxidation (SPO) coupled with methanogenesis is often
      inhibited under high ammonium concentrations in anaerobic digesters. However, the
      inhibitory mechanism remains poorly understood. We conducted two independent
      laboratory experiments with a swine manure digester sludge. In experiment I, RNA
      based stable isotope probing (SIP) was applied to determine the active players of
      both bacteria and methanogens involved in SPO under different ammonium
      concentrations (0, 3 and 7 g NH4+N L-1). In experiment II, the dynamics of the
      bacterial community under ammonia stress was monitored using the 16S rRNA
      pyrosequencing and quantitative PCR under similar conditions as in experiment I
      but without the addition of external propionate. An additional higher ammonium
      treatment (10 g NH4+N L-1) was applied in experiment II to maximize the ammonia
      stress. We identified that the Smithella bacteria and the Methanosaetaceae and
      Methanospirillaceae archaea were the most active players involved in SPO and
      methanogenesis. We revealed that Smithella, Methanosaetaceae and
      Methanospirillaceae were moderately and severely inhibited at 3 and 7-10 g NH4+N
      L-1, respectively. However, the fermentative bacteria appeared to be more
      tolerant to ammonia stress. The microbial responses were corroborated with the
      accumulation of VFAs and the repression of methanogenesis under high ammonium
      conditions.

PMID- 30278383
TI  - Fc-gamma receptor IIA and IIIA variants in two African cohorts: Lack of
      consistent impact on heterosexual HIV acquisition, viral control, and disease
      progression.
AB  - Human Fc-gamma receptors (FcgammaRs) FcgammaRIIA and FcgammaRIIIA contain amino
      acid variants with both high and low affinities for IgG that modulate antibody
      mediated effector functions. Recent HIV vaccine trials suggested that these
      FcgammaR variants can influence susceptibility to HIV infection, which prompted
      us to fully assess the role of FcgammaR variants on HIV acquisition, viral
      control, and disease progression in two longitudinal heterosexual transmission
      cohorts with HIV subtypes A and C as the major circulating viruses. For 836
      participants, molecular genotyping resolved genetic variations encoding the
      FcgammaRIIA (131 H/R) and FcgammaRIIIA (158 V/F) single nucleotide polymorphisms.
      Kaplan-Meier curves, Cox proportional hazards models, and linear regression
      models did not reveal any clear or consistent FcgammaR association with time to
      HIV acquisition, viral load in early infection, or extent of CD4 + T-cell decline
      over time after infection. Overall, previous epidemiological findings on FcgammaR
      variants and vaccine efficacy are not readily applicable to heterosexual HIV
      transmission.

PMID- 30278384
TI  - Broad-spectrum antiviral JL122 blocks infection and inhibits transmission of
      aquatic rhabdoviruses.
AB  - The aquaculture industry is growing rapidly to meet the needs for global protein
      consumption. Viral diseases in aquaculture are quite challenging due to lack of
      treatment options as well as limited injection-delivery vaccines, which are
      costly. Thus, water-immersion antiviral treatments are highly desirable. This
      study focused on broad-spectrum, light-activated antivirals that target the viral
      membrane (envelope) of viruses to prevent viral-cell membrane fusion, ultimately
      blocking viral entry into cells. Of the tested small-molecules, JL122, a new
      broad-spectrum antiviral previously unexplored against aquatic viruses, blocked
      infection of three aquatic rhabdoviruses (IHNV, VHSV and SVCV) in cell culture
      and in two live fish challenge models. Importantly, JL122 inhibited transmission
      of IHNV from infected to uninfected rainbow trout. Further, the effective
      antiviral concentrations were not toxic to cells or susceptible fish. These
      results show promise for JL122 to become an immersion treatment option for
      outbreaks of aquatic enveloped viral infections.

PMID- 30278385
TI  - Comparison of postmortem butane distribution between two fatal butane poisoning
      cases.
AB  - Fatal accidents during butane abuse frequently occur in Japan and in many
      countries around the world. Although analytical data about butane concentration
      in postmortem samples is being accumulated, when using the data to determine the
      cause of death, careful interpretation is required because the gas is easily
      diffused. Two fatal butane poisoning cases were encountered, and butane
      quantification of autopsy samples obtained from left and right heart blood,
      femoral blood, kidney, liver, lung, brain and fatty tissues was performed. In
      both cases, butane concentration in the left heart blood was lower than in the
      right heart blood or the femoral blood, despite gas inhalation. These findings
      may indicate that the deceased individuals interrupted gas inhalation and inhaled
      room air immediately before their death, therefore ruling out asphyxia due to
      anoxia as the mechanism of death. Case 1, which was suspected to be a not acute
      death, showed a very high butane concentration ratio of fatty tissues to femoral
      blood of over 70. Case 2 was considered an acute death, and the butane
      concentration ratio of fatty tissues to femoral blood was 8.2. These results are
      consistent with previously reported findings showing that much higher ratios of
      fatty tissues to blood are compatible with long survival time. In conclusion, the
      comparison of butane concentration among different samples, including left heart
      blood versus right heart blood and fatty tissues versus blood, is useful when
      interpreting the result of postmortem butane analysis to examine the mechanism of
      death and survival time.

PMID- 30278386
TI  - Two loci concurrent mutations in non-exclusion parentage cases using 19 STR
      profiles.
AB  - Two loci concurrent mutations in non-exclusion paternity case were reported based
      on 19 STR loci available from GoldeneyeTM DNA ID System 20A (Peoplespot, Beijing,
      China). When 9508 family trios with Paternity index (PI) threshold of >10,000 was
      analyzed, 14 families show mutations at two loci. The paternity was confirmed by
      using an additional 19 STR markers. When the probability of occurrence of two
      mutations was compared with the expected probability deduced from binomial model,
      the observed mutational probability was significantly larger than the
      expectation. However, the characteristics of mutations agree with those reported
      previously. Our result indicates that larger samples is still need to estimate
      mutation rates accurately and reveal the relationship between mutations with
      multiple loci and the characterization of human mutations based on
      microsatellites.

PMID- 30278387
TI  - Electrooculogram and submandibular montage to distinguish different eye, eyelid,
      and tongue movements in electroencephalographic studies.
AB  - OBJECTIVE: We propose an electrooculogram and submandibular montage that helps to
      discriminate eye/eyelid/tongue movements and to differentiate them from
      epileptiform activity or slowing on electroencephalography (EEG). METHODS: We
      analyzed different eye/eyelid and tongue movements in 6 and 4 patients,
      respectively. Six peri-orbitally and one submandibular electrodes were placed. We
      referred these electrodes to an indifferent reference (Cz/Pz) and we recorded
      eye/eyelid and tongue movements simultaneously with the 10-20 system EEG.
      Additionally, we analyzed 2 seizures with the electrooculogram montage. RESULTS:
      The electrooculogram deflections always showed an opposite phase direction when
      eye/eyelid movements occurred. Conversely, epileptiform activity produced
      deflections in the same phase direction in all electrooculogram electrodes. The
      electrooculogram montage was able to distinguish eye ictal semiology. Vertical
      tongue movements showed opposite phase deflections between the submandibular and
      the inferior ocular electrodes. Horizontal tongue movements revealed opposite
      phase reversal deflections between both inferior ocular electrodes. CONCLUSIONS:
      The proposed montage accurately defines different eye/eyelid and tongue movements
      from brainwave activity. Additionally, it is useful to differentiate eye/eyelid
      movements from epileptiform activity and to characterize ictal ocular semiology,
      which can help localize or lateralize the epileptogenic zone. SIGNIFICANCE: We
      propose this new montage to provide added value to prolonged video-EEG studies.

PMID- 30278388
TI  - Impaired performance of patients with writer's cramp in complex fine motor tasks.
AB  - OBJECTIVE: Writer's cramp (WC) is a task-specific focal dystonia. WC is
      characterized by involuntary contractions of muscles of the hand and arm during
      handwriting, resulting in impaired writing with exaggerated finger forces. The
      generalization of symptoms to other fine motor tasks is widely discussed. The aim
      of the study was to determine affected fine motor aspects with an extensive
      testing battery. METHODS: Twelve people with WC and twelve healthy controls were
      examined. Performance in the Jebsen-Taylor Hand Function Test, Nine-Hole-Peg Test
      and 2-point discrimination was evaluated. To analyze object manipulation skills,
      we examined grip forces, temporal measures and other aspects of force control
      during (1) lifting actions with variations of weight and surface (2) cyclic
      movements (3) visuomotor tracking (4) fast force changes and (5) grip strength.
      In addition, correlation between the dependent variables of the fine motor tasks
      and the handwriting deficits was assessed. RESULTS: WC patients had impaired
      performance in the visuomotor tracking task (root mean square error (RMSE), p =
      0.03 and time lag, p = 0.05) and the fast force changes (frequency, p = 0.01).
      There were no statistically significant group differences in the other tasks. We
      found a correlation between the RMSE of the tracking task and the time needed to
      write the test sentence (r = 0.643, p = 0.01). CONCLUSION: WC patients revealed
      abnormalities in complex fine motor performance in tasks with high demands on
      coordination and visual components, specifically in tracking and fast force
      changes. SIGNIFICANCE: This suggests a deficit in visuomotor integration,
      coordination and cognitive aspects related to movement processing particularly
      with respect to low forces. These insights may prove useful in the development of
      targeted training approaches.

PMID- 30278389
TI  - Automated EEG source imaging: A retrospective, blinded clinical validation study.
AB  - OBJECTIVE: To evaluate the accuracy of automated EEG source imaging (ESI) in
      localizing epileptogenic zone. METHODS: Long-term EEG, recorded with the standard
      25-electrode array of the IFCN, from 41 consecutive patients with focal epilepsy
      who underwent resective surgery, were analyzed blinded to the surgical outcome.
      The automated analysis comprised spike-detection, clustering and source imaging
      at the half-rising time and at the peak of each spike-cluster, using individual
      head-models with six tissue-layers and a distributed source model (sLORETA). The
      fully automated approach presented ESI of the cluster with the highest number of
      spikes, at the half-rising time. In addition, a physician involved in the
      presurgical evaluation of the patients, evaluated the automated ESI results (up
      to four clusters per patient) in clinical context and selected the dominant
      cluster and the analysis time-point (semi-automated approach). The reference
      standard was location of the resected area and outcome one year after operation.
      RESULTS: Accuracy was 61% (95% CI: 45-76%) for the fully automated approach and
      78% (95% CI: 62-89%) for the semi-automated approach. CONCLUSION: Automated ESI
      has an accuracy similar to previously reported neuroimaging methods.
      SIGNIFICANCE: Automated ESI will contribute to increased utilization of source
      imaging in the presurgical evaluation of patients with epilepsy.

PMID- 30278390
TI  - Atypical perceptual and neural processing of emotional prosodic changes in
      children with autism spectrum disorders.
AB  - OBJECTIVE: The present study explored the processing of emotional speech prosody
      in school-aged children with autism spectrum disorders (ASD) but without marked
      language impairments (children with ASD [no LI]). METHODS: The mismatch
      negativity (MMN)/the late discriminative negativity (LDN), reflecting pre
      attentive auditory discrimination processes, and the P3a, indexing involuntary
      orienting to attention-catching changes, were recorded to natural word stimuli
      uttered with different emotional connotations (neutral, sad, scornful and
      commanding). Perceptual prosody discrimination was addressed with a behavioral
      sound-discrimination test. RESULTS: Overall, children with ASD (no LI) were
      slower in behaviorally discriminating prosodic features of speech stimuli than
      typically developed control children. Further, smaller standard-stimulus event
      related potentials (ERPs) and MMN/LDNs were found in children with ASD (no LI)
      than in controls. In addition, the amplitude of the P3a was diminished and
      differentially distributed on the scalp in children with ASD (no LI) than in
      control children. CONCLUSIONS: Processing of words and changes in emotional
      speech prosody is impaired at various levels of information processing in school
      aged children with ASD (no LI). SIGNIFICANCE: The results suggest that low-level
      speech sound discrimination and orienting deficits might contribute to emotional
      speech prosody processing impairments observed in ASD.

PMID- 30278391
TI  - Cognitive load of walking in people who are blind: Subjective and objective
      measures for assessment.
AB  - BACKGROUND: Although walking without vision seems to carry a high cognitive cost,
      few studies have measured the cognitive load involved in this activity in blind
      people. The aim of this study was to assess the cognitive load of walking in
      blind people, using gait analysis, a dual task paradigm and a subjective
      assessment of cognitive load. METHODS: In a quantitative quasi-experimental
      design, 25 blind adults walked 40 meters. In one trial, participants walked
      normally (control condition). In another, they walked while performing an
      auditory simple reaction time task, and in the third trial they walked, performed
      the simple reaction time task and avoided obstacles. In addition to the simple
      reaction time task performance, walking speed was recorded, and participants
      provided a subjective assessment of cognitive load after each trial. Performance
      of participants aged less than 60 years were compared with those aged over than
      60 years. RESULTS: Walking significantly reduced performance of the simple
      reaction time task; carrying out the simple reaction time task while walking
      significantly reduced walking performance and increased the subjective assessment
      of cognitive load; and simple reaction time task performance decreased and
      subjective assessment increased when obstacles were present. Few significant age
      effects were found. SIGNIFICANCE: Walking without vision involves a cognitive
      load that increases when the environment becomes complex. Each of the three
      methods used is relevant when assessing the cognitive load involved in walking in
      blind people, and could be useful in rehabilitation intervention. The results
      obtained allowed recommendations to be suggested for the design of technological
      mobility devices.

PMID- 30278392
TI  - Microcystin and pyriproxyfen are toxic to early stages of development in Rhamdia
      quelen: An experimental and modelling study.
AB  - The recent increase of freshwater eutrophication has favored cyanobacteria blooms
      and consequently the increase of toxins such as microcystin-LR in aquatic
      environments, but few is know about the associated effect of toxin and other
      compounds. Pyriproxyfen is an insecticide indicated by WHO (World Health
      Organization) to control Aedes aegypti mosquito (vector of Dengue, Chikungunya
      and Zika diseases), however, the effects are not well described to non-target
      species, such as fish. The early life stages (ELS) of fish are more sensitive to
      chemical stress due to higher metabolic rate, immature immune system and high
      superficial area/volume ratio. In the current study, ELS of R. quelen a
      Neotropical fish were exposed to environmentally realistic concentrations of
      microcystin (1, 10 and 100 ug L-1; M1, M2 and M3 groups, respectively) from an
      algal extract, pyriproxyfen (1 and 10 ug L-1, P1 and P2) and their association
      (co-exposure). The hatching, survival and larvae deformities were analyzed, and
      applied a mathematical model to evaluate the effects on the population size along
      further generations. Both compounds were toxic to embryos/larvae of fish, but the
      effects were more pronounced in M2, P1M2 and P2M1 for hatching and M2, P1M2, P2M1
      and P1 for survival. Deformities prevailed in groups exposed to the chemicals at
      48 hpf (hours post-fertilization) were suggestions of toxicological interaction
      in P1M2, P2M1 and P2M2 at 48 and 72 hpf. In 96 hpf, the levels of deformities
      were lower than in previous times. Model predicted population density over 100
      years decreased to lower than 0.5 (50%) in all groups, except for P1M1,
      indicating risk of extinction. P1M2 had the worse results, followed by M2, P1M3
      and P2M1. Cyanobacterial blooms can lead to microcystin-LR levels higher than M2
      (10 ug L-1), and the suggestion of toxicological interaction with pyriproxyfen is
      relevant because both compounds may potentially coexist in aquatic environments.
      Finally, mathematical models may provide an ecological interpretation of the risk
      of exposure of fish.

PMID- 30278393
TI  - Occurrence, distribution and risk assessment of pesticides in a river-reservoir
      system.
AB  - The water environment from river to reservoir has been considered as a hybrid
      river-reservoir system due to pronounced environmental properties. This study
      investigated the distribution and potential environmental behavior of pesticides
      in river-reservoir system, examining 31 target pesticides in water phase from a
      key drinking water source (Dongjiang River). The concentrations of ?8OCPs,
      ?16OPPs and ?7SPs with the corresponding occurrence were in the range of 107.57
      340.35 ng/L (moderate level), 232.65-1197.95 ng/L (moderate level) and 125.23
      245.09 ng/L (low level), respectively. Ecological risk assessments indicated that
      most of the pesticides posed a high level of risk to the aquatic organisms.
      Moreover, seasonal agricultural application, rainfall and temperature could
      influence the levels and compositions of ?8OCPs, ?16OPPs and ?7SPs in the river
      system, while seasonal hydrological processes could only influence their
      compositions in the reservoir system. In the wet season, the levels of ?8OCPs and
      ?7SPs decreased from the river system to reservoir system probably via
      biogeochemical processes, while the level of ?16OPPs decreased along the
      environmental gradient probably via dilution process. Additionally, longer
      hydraulic retention time of the reservoir system could contribute to the
      biogeochemical processes for OPPs and SPs exported from the river system, but it
      might fail to facilitate this process for OCPs. Taken together, this study
      highlighted that the distributions and environmental behavior of pesticides in
      river-reservoir system varied seasonally from river system to reservoir system.

PMID- 30278394
TI  - Response of soil enzymes, functional bacterial groups, and microbial communities
      exposed to sudan I-IV.
AB  - As an important type of typical synthetic azo dyes, the use of sudan I-IV dyes
      has been of concern worldwide because of their wide applications and illegal
      addition into various foodstuffs, potentially resulting in water and soil
      pollution and having adverse effects on human health and ecosystems. However, to
      date, little has been reported regarding the environmental levels of these dyes
      and the risks that they pose to human health and ecosystems. Understanding the
      responses of soil enzymes, functional groups of bacteria and microbial
      communities to sudan dyes is of great importance to reveal their effect on the
      soil environment. In this study, we performed a toxicological study on the
      specific and overall effects of sudan I-IV dyes on the activity of soil enzymes
      including catalase, urease, and alkaline phosphatase after a 2- and 7-day
      exposure, functional groups of soil bacteria including nitrogen-fixing, ammonia
      oxidizing, and denitrifying bacteria on day 14, and the structure and diversity
      of soil microbial community compositions on day 30. The results showed that sudan
      I-IV affected the activity of the soil enzymes, the abundance of the bacterium
      functional groups, and the structure and diversity of microbial community
      compositions, and the effects varied by sudan dyes I-IV, the exposure
      concentration, and the exposure time.

PMID- 30278395
TI  - Impairment of learning and memory of mice offspring at puberty, young adulthood,
      and adulthood by low-dose Cd exposure during pregnancy and lactation via GABAAR
      alpha5 and delta subunits.
AB  - Cadmium (Cd) is a pervasive carcinogen and environmental endocrine disruptor. We
      studied the changes in learning and memory of offspring mice, whose mothers were
      exposed to 10 mg Cd/L via the drinking water during pregnancy and lactation
      period, as well as the changes of testosterone and estrogen levels, serum Cd
      levels, the histopathological changes and the changes in the mRNA and protein
      levels of different subunits of gamma-aminobutyric acid receptor subtype A
      subunits (GABAARs) in the hippocampus at the prepuberty, puberty, young adult,
      and adult stages. At birth, Cd had no obvious effect on mice offspring as
      statistically accessed based on their body weight, body length, and tail length
      (all p > 0.05). After grouped, the serum Cd levels increased in the three exposed
      groups more than in the normal control group at stages (all p < 0.05). Only serum
      estradiol of female offspring at age 7 weeks was significantly decreased compared
      with other groups (all p < 0.05). Histopathological results showed that the
      arrangement of the cells in hippocampal CA1 area of mice offspring was
      significantly sparse in the exposed groups compared with the control group. At 5
      and 7 weeks, two Cd-exposed groups showed prolonged escape latency and exploring
      time for the platform compared with the normal group in the Morris water maze
      (all p < 0.05). Only increased protein expression of GABAARalpha5 was found in
      the Cd group at these two ages. At age 12 weeks, similar impaired learning and
      memory of female mice, and decreased protein expression of GABAARdelta was found
      in Cd-exposed groups. Collectively, low-dose Cd had no effect on the growth of
      mice offspring but affected their learning and memory, especially female
      offspring, at puberty, young adulthood, and adulthood through changed structure
      in the hippocampal CA1 area and protein expression of GABAARalpha5 and
      GABAARdelta.

PMID- 30278396
TI  - Distribution, pollution, bioaccumulation, and ecological risks of trace elements
      in soils of the northeastern Qinghai-Tibet Plateau.
AB  - Environmental quality of the northeastern Qinghai-Tibet Plateau has attracted
      more attention due to increasing anthropogenic disturbance. Therefore, this study
      investigated the distribution, pollution, ecological risks, and bioaccumulation
      of 12 target heavy metals and 16 rare earth elements (REEs) in soils of this
      area. The average concentrations of target trace elements in soils ranged from
      0.16 (Hg) to 500.46 (Cr) mg/kg. Pb caused more serious pollution than the other
      elements based on geo-accumulation index evaluation. Hg exhibited the strongest
      enrichment feature with the average enrichment factor of 8.41. Compare with
      modified contamination degree and pollution load index, Nemerow pollution index
      method obtained the most serious evaluation results that 45.67% and 16.54% of
      sampling sites possessed high and moderate pollution. Evaluation results of
      potential ecological risk index showed that trace elements in soils posed very
      high and considerable ecological risks in 34.65% and 7.09% of sampling sites,
      respectively. Mining area was the region with the most serious pollution and
      ecological risks. Average bioaccumulation factor (BCF) values of target trace
      elements ranged from 0.05 (REEs) to 2.67 (Cr). Cr was the element that was easier
      to bio-accumulate in plants of the study area than the other target elements. It
      is in urgent need to take effective measures for controlling current pollution
      and potential ecological risks of trace elements in soils of the northeastern
      Qinghai-Tibet Plateau.

PMID- 30278397
TI  - Assessing mercury pollution in Amazon River tributaries using a Bayesian Network
      approach.
AB  - Mercury pollution of water bodies exerts significant human and ecosystem health
      impacts due to high toxicity. Relatively high levels of mercury have been
      detected in the Amazon River and its tributaries and associated lakes. The study
      employed a Bayesian Network approach to investigate the contribution from
      geogenic sources to mercury pollution of lakes in the Madeira River basin, which
      is the largest tributary of the Amazon River. It was found that the source
      indicators of naturally occurring mercury have both, positive and negative
      relationships with mercury in lake sediments. Although the positive relationships
      indicated the influence of geological and soil formations, the negative
      relationships implied that the use of mercury amalgam for gold extraction in
      artisanal and small-scale mining (ASM), which is the primary anthropogenic source
      of mercury, also contribute to mercury in Amazon tributaries. This was further
      evident as mercury concentrations in lake sediments were found to be
      significantly higher than those in the surrounding rocks. However, potential
      anthropogenic mercury was attributed to historical inputs from gold mining due to
      the recent decline of ASM mining practice in the region.

PMID- 30278398
TI  - Sub-lethal UV radiation during early life stages alters the behaviour, heart rate
      and oxidative stress parameters in zebrafish (Danio rerio).
AB  - Environmental UV radiation in sufficient doses, as a possible consequence of
      climate change, is potent enough to affect living organisms with different
      outcomes, depending on the exposure life stage. The aim of this project was to
      evaluate the potentially toxic effects of exposure to sub-lethal and
      environmentally relevant doses of UVA (9.4, 18. 7, 37.7 J/cm2) and UVB radiation
      (0.013, 0.025, 0.076 J/cm2) on the development and behaviour in early life stages
      (4.5-5.5 h post fertilization, hpf) of the zebrafish (Danio rerio). The used
      doses were all below the median lethal dose (LD50) and caused no significant
      difference in survival, deformities, or hatching between exposed and control
      groups. Compared to controls, there were transient UVA and UVB exposure effects
      on heart rate, with dose dependent reductions at 50 hpf, and at 60 hpf for UVA
      only. The UVB exposure caused an increasing trend in reactive oxygen species
      (ROS) formation at the two highest doses, even though only significant at 120 hpf
      for the second highest dose. Both UVA and UVB caused an increasing trend in lipid
      peroxidation (LPO) at the highest doses tested at 72 hpf. Furthermore, UVA
      exposure led to significant reductions in larval movement following exposure to
      the two highest doses of UVA, i.e., reduction in the time spent active and the
      total distance moved compared to control at 100 hpf, while no effect on the
      swimming speed was observed. The lowest dose of UVA had no effect on behaviour.
      In contrast, the highest dose of UVB led to a possible increase in the time spent
      active and a slower average swimming speed although these effects were not
      significant (p = 0.07). The obtained results show that UV doses below LD50 levels
      are able to cause changes in the behaviour and physiological parameters of
      zebrafish larvae, as well as oxidative stress in the form of ROS formation and
      LPO. Further testing is necessary to assess how this type of radiation and the
      effects observed could affect fish population dynamics.

PMID- 30278399
TI  - Land use impact on potentially toxic metals concentration on surface water and
      resistant microorganisms in watersheds.
AB  - Soil and water resources must be conserved and protected. However, the management
      of production activities causes a change in the quality of these natural
      resources due to accumulation in soil of potentially toxic metals. The objective
      of the present study was to identify the variety and paths of potentially toxic
      metals (PTMs), such as cadmium, lead, copper, chromium, nickel and zinc, which
      are associated spatially and temporally to soil and water. We also intended to
      isolate bacteria resistant to PTMs with important characteristics to be used in
      bioremediation processes. Water samples were collected every two months for one
      year (February-December/2014) at eight sites (P1-P8) and the soil samples were
      collected twice (February and August/2014) from twelve sites (S1-S12). Results
      indicated that agricultural land use impacts the environment, increasing the
      concentration of potentially toxic metals, mainly copper, zinc and chromium, in
      soil and water due to crop management. Ten bacteria resistant to all the metals
      studied were isolated, which could be used as tools for bioremediation of
      contaminated soils and water with those metals. The results would positively
      contribute to land use policy, and for the development of enhanced agricultural
      practices.

PMID- 30278400
TI  - Capacity of tissue water regulation is impaired in an osmoconformer living in
      impacted estuaries?
AB  - Estuarine osmoconformes rely on their ability to perform tissue and cell water
      regulation to cope with daily osmotic challenges that occur in the estuary. In
      addition, these animals currently must deal with pollutants present in the
      estuarine environment, which can disturb their capacity of water regulation. We
      collected the mangrove oyster Crassostrea rhizophorae in two tropical estuaries
      in the Northeast region of Brazil with different degrees of human interference:
      the Paraiba Estuary (impacted) and the Mamanguape Estuary (preserved). Tissue
      water content was analyzed after exposure to salinities 12, 24 and 36 for 24 h.
      Gill cell volume regulation was analyzed in vitro upon hypo- and hyper-osmotic
      conditions. We also analyzed gill MXR (multi-xenobiotic resistance) mechanism, as
      reference of environmental pollution. Gill and muscle of oysters from two sites
      of Paraiba Estuary, and from one site of Mamanguape Estuary were not able to
      maintain tissue water content upon hypo- and hyper-osmotic conditions. Gill cells
      of oyster from the same sites exhibited swelling followed by regulatory volume
      decrease upon hypo-osmotic condition. Gill MXR activity was increased in oysters
      from these sites. The best tissue and cell water regulation, and the lowest MXR
      activity, was found in oyster from downstream of Mamanguape Estuary, our
      reference site and the one most preserved. Tissue and cell water regulation
      proved to be a sensitive parameter to environmental pollution and could be
      considered as biomarker of aquatic contamination.

PMID- 30278401
TI  - Effects of softwood biochar on the status of nitrogen species and elements of
      potential toxicity in soils.
AB  - The effects of softwood-derived biochar materials on the chemical behaviour of
      environmental contaminants in soils were examined in two microcosm scenarios.
      Addition of the biochar materials into an alkaline sandy soil significantly
      reduced NH3 volatilization and made it available for conversion into NO3- via
      nitrification. This process could be enhanced by an increased application rate of
      biochar produced at a higher pyrolysis temperature. Under the alkaline conditions
      encountered in the experiment, the biochar surfaces tended to be negatively
      charged which disfavours the adsorption of NO3-. Therefore, in a fully open
      system, the addition of biochar materials was likely to contribute to nitrate
      leaching from the fertilized alkaline sandy soil. The effects of the biochar
      materials on the immobilization of Fe2+ generated via anaerobic iron reduction in
      the inundated contaminated soil were not observed, except for the treatment with
      a higher dose of biochar material produced under pyrolysis temperature at 700 
      degrees C after the 240th h of incubation. Arsenic showed similar behaviour to
      Fe. Zn tended to have a higher affinity to the biochar, as compared to Mn.
      Immobilization of Pb occurred regardless of whether or not the biochar is
      present.

PMID- 30278402
TI  - Environmental hazard and risk assessment of thiochemicals. Application of
      integrated testing and intelligent assessment strategies (ITS) to fulfil the
      REACH requirements for aquatic toxicity.
AB  - REACH requires information on hazardous properties of substances to be generated
      avoiding animal testing where possible. It is the objective of the present case
      study with thiochemicals to extract as much information as possible from
      available experimental data with fish, daphnia and algae and to fill data gaps
      for analogues to be registered under REACH in 2018. Based on considerations of
      chemical similarity and common mode of action (MOA) the data gaps regarding the
      aquatic toxicity of the thiochemicals were largely closed by trend analysis
      ("category approach") and read-across within the same group, for example,
      thioglycolates or mercaptopropionates. Among 16 thiochemicals to be registered by
      2018 there are only 2 substances with sufficient data. 36 data gaps for 14
      thiochemicals were identified. Most of the required data (>60%) could be
      estimated by in silico methods. Only 14 tests (6 algae, 6 daphnia, 1 limit fish
      test and 1 acute fish test) were proposed. When the results of these tests are
      available it has to be discussed whether 2 further fish (limit) tests are
      required. For two substances (exposure-based) waiving was suggested. The
      relatively high toxicity of the thiochemicals is manifested in low predicted no
      effect concentrations (PNECs). Only preliminary predicted environmental
      concentrations (PECs) could be derived for the thiochemicals for which a risk
      assessment has to be performed (production rate >10 t/y). The preliminary
      PEC/PNEC ratios indicate no risk for the aquatic compartment at the production
      site. PECs due to down-stream use must not exceed the estimated PNECs.

PMID- 30278403
TI  - A review of the implications and challenges of manganese removal from mine
      drainage.
AB  - Manganese (Mn) is the third most abundant transition metal in the Earth's crust.
      Decades of increasing worldwide mining activities have inevitably led to the
      release of large amounts of this metal into the environment. Mine drainage,
      either acidic or neutral, often contains high levels of Mn, which have
      potentially detrimental effects on ecosystems and receiving water bodies. This
      review provides a comprehensive assessment of the main implications and
      challenges of Mn treatment in mine drainage. With this aim, the beneficial and
      adverse effects of Mn on ecosystems and human health are presented first. A
      comparison of background and mine effluents Mn contents is also provided, further
      stressing the need for Mn removal from mine drainage. Several technical options
      to address Mn contamination in acid and neutral mine drainage, and the challenges
      associated with Mn removal, are subsequently discussed. Thus, this paper presents
      up-to-date knowledge on the available physicochemical and biological processes
      deemed operative in Mn removal during mine drainage treatment and their
      limitations considering the distinctive behavior of Mn. The discussion is further
      extended to passive treatment systems, which are the most commonly implemented
      systems for mine drainage treatment on abandoned or closed mine sites, and
      highlights both their design criteria and operation requirements, as well as the
      factors that influence Mn removal efficiency. Finally, new perspectives on future
      research and development needs are identified to address the challenges in Mn
      removal during mine drainage treatment.

PMID- 30278404
TI  - Multiple biomarkers based appraisal of deltamethrin induced toxicity in silver
      carp (Hypophthalmichthys molitrix).
AB  - Deltamethrin (DLM) is alpha-cyano (type II) synthetic pyrethroid. DLM exposure
      leads to strong neurotoxic effects and a number of complex toxicological
      syndromes. The current study assessed DLM mediated oxidative stress, behavioral,
      hematological, histopathological, and biochemical toxic effects on silver carp
      (Hypophthalmichthys molitrix). Exposure to an acute concentration (2 MUg/L) of
      DLM resulted in different behavioral inconsistencies and a time-dependent
      significant (P < 0.05) change in the hematology and serum biochemistry of silver
      carp. A significant (P < 0.05) increase in the activities of reactive oxygen
      species, lipid peroxidation, and antioxidant enzymes whereas a significant
      decrease in total protein contents in the liver, gills, brain, and muscle tissues
      were observed. DLM exposure increased the activities of metabolic enzymes in the
      gills, muscles, and liver of silver carp. A significant (P < 0.05) increase in
      DNA damage in peripheral blood erythrocytes was evident. DLM exposure led to a
      time-dependent significant (P < 0.05) increase in the whole-body cortisol and
      blood glucose level, while a significant decrease in acetylcholine esterase
      activity in the brain, liver, and muscle tissues. Different histopathological
      changes in the liver, gills, brain, and intestine were observed, however, no
      significant change in the gross anatomy and morphometric parameters of the fish
      was observed. The current study provides valuable information for devising better
      strategies regarding environmental management, chemicals' risk assessment,
      biodiversity conservation, and monitoring of the aquatic organisms. DLM was
      concluded to be highly toxic to fish. The extensive use of DLM should be
      prohibited or allowed under strict environmental laws; otherwise, it might lead
      to the extermination of the susceptible wildlife, such as commercially very
      valuable but nearly threatened silver carp.

PMID- 30278405
TI  - A mixture of Persistent Organic Pollutants (POPs) and Azoxymethane (AOM) show
      potential synergistic effects on intestinal tumorigenesis in the A/J Min/+ mouse
      model.
AB  - A multitude of cancer types, including breast, testicular, liver and colorectal
      cancer, have associations with exposure to Persistent Organic Pollutants (POPs).
      The present study aimed to investigate whether a mixture of POPs could affect
      intestinal tumorigenesis in the A/J Min/+ mouse, a model for human colorectal
      cancer (CRC). Pollutants were selected for their presence in Scandinavian food
      products and the mixture was designed based on defined human estimated daily
      intake levels. Mice were exposed through the diet, at control, low and high
      mixture concentrations, for 10 weeks. In a separate experiment, mice also
      received one subcutaneous injection of Azoxymethane (AOM) to explore whether this
      carcinogenic compound influenced the effect of the POPs. Intestinal tumorigenesis
      was examined by surface microscopy and histopathology. Moderate and dose
      dependent increases in tumorigenesis were observed after dietary POP exposure.
      The AOM treatment alone stimulated the growth of colonic lesions, but did not
      increase the formation of new lesions. Combined AOM treatment and POP exposure
      demonstrated a synergistic effect on lesion formation in the colon, and to a
      lesser extent in the small intestine. This synergy was also evident by an
      increased number of malignant colonic tumors (carcinomas). In conclusion, the
      study shows that a mixture of POPs interacted synergistically with a known
      carcinogen (AOM), causing increased intestinal tumorigenesis in the A/J Min/+
      mouse model.

PMID- 30278406
TI  - The role of electrical impedance tomography for monitoring during bronchoscopy: A
      case report.
AB  - Continuous monitoring of lung ventilation can be useful in treating patients
      admitted to the intensive care unit (ICU). Electrical impedance tomography (EIT)
      has been used as a relatively new imaging technique for this purpose. We
      presented a patient with pneumonia who was admitted to the ICU after pulmonary
      thromboembolism (PTE) required to perform bronchoalveolar lavage (BAL). A
      drainage procedure and subsequent improvement in pulmonary function were
      monitored using EIT contributed to the treatment process. The patient has been
      discharged from the hospital with an improved general condition.

PMID- 30278409
TI  - Temperament and character profiles for children with ADHD with and without tic
      disorders.
AB  - There is no research about whether ADHD with tic disorder that temperamental
      features that differ from the ADHD. This research aimed to identify temperament
      and character profiles for children with ADHD according to tic disorder by
      comparing them with a healthy control group. A discriminant analysis was
      conducted to identify whether temperament and character profiles can discriminate
      comorbidity. The sample consisted of three groups (N = 40 per group): ADHD alone,
      ADHD with tic disorder and age- and sex- matched healthy control. The parents of
      120 children (mean age 8.57 +/- 1.71 years) completed the Junior Temperament and
      Character Inventory (JTCI). The two ADHD groups showed higher novelty seeking and
      low persistence, self-directedness and cooperativeness than the control group.
      The ADHD alone group had lower scores for persistence and self-directedness than
      the other two groups. Temperament and character profiles were useful for
      discriminating ADHD from the control group. However, their discriminating power
      was relatively low for all three groups. Results indicated that differences in
      temperament and character in ADHD children were present according to comorbid tic
      disorders. JTCI's discriminating power for ADHD alone and ADHD with tic disorder
      was relatively lower than that of the combined ADHD group and the control group.

PMID- 30278408
TI  - Adherence, insight and disability in paranoid schizophrenia.
AB  - Insight has long been linked to both prognosis and functioning in patients with
      schizophrenia; likewise, it is key to treatment adherence. This study seeks to
      assess the association between insight, adherence to pharmacological treatment,
      and disability in schizophrenia, and to study the potential mediating role of
      adherence between insight and disability. Insight (SUMD), adherence (CRS), and
      disability (WHO-DAS) were measured in 80 clinically stable patients with DSM-IV
      TR paranoid schizophrenia. Psychopathology was assessed with the Positive and
      Negative Syndrome Scale (PANSS). In a first step, predictors of disability were
      identified using linear regression to identify variables related to disability
      and further a mediation analysis was carried out. Negative symptoms, insight, and
      adherence account for 54.2% of the variance in disability. Negative symptoms act
      directly on disability, while the effect of insight on disability is partially
      mediated by adherence. Insight is key in disability in schizophrenia and should
      be leveraged in treatment programs.

PMID- 30278407
TI  - P(v-a)CO2/C(a-v)O2-directed resuscitation does not improve prognosis compared
      with SvO2 in severe sepsis and septic shock: A prospective multicenter randomized
      controlled clinical study.
AB  - PURPOSES: The present study examined the value of P(v-a)CO2/C(a-v)O2 compared
      with ScvO2 as a target for clinical resuscitation of severe sepsis/septic shock.
      MATERIALS AND METHODS: 228 patients were randomly divided into a P(v-a)CO2/C(a
      v)O2-targeted and a ScvO2-targeted therapy group. The effects on hemodynamics,
      interventional intensity, and outcome were recorded and analyzed. RESULTS: The
      mean arterial pressure (MAP) of the P(v-a)CO2/C(a-v)O2-targeted therapy group was
      significantly higher at 3 h, 12 h, 24 h, and 3 days (P < .05). The P(v-a)CO2/C(a
      v)O2 of the ScvO2-targeted therapy group was significantly higher at each time
      point after resuscitation (P < .05). However, the CVP, lactate, urine output,
      ScvO2, and P(v-a)CO2 were not significantly improved. The P(v-a)CO2/C(a-v)O2
      targeted therapy group used a smaller fluid volume and required fewer red blood
      cell transfusions and vasoactive drugs, but these results were also not
      significant. There were no differences between 28-day and 60-day mortality,
      APACHEII and SOFA scores, ICU length of stay, residence length of stay, number of
      days free of vasoactive drugs, or number of ventilator-free days. Post hoc tests
      revealed no significant differences between these two groups in 28-day survival.
      CONCLUSION: P(v-a)CO2/C(a-v)O2-directed resuscitation did not improve prognosis
      compared with ScvO2 in severe sepsis and septic shock. ClinicalTrials.gov
      Identifier NCT01877798.

PMID- 30278410
TI  - Insecure attachment as a factor in hoarding behaviors in a non-clinical sample of
      women.
AB  - Hoarding is linked to ambivalence and uncertainty about one's self and others.
      These notions are close to those constituting attachment representations.
      Hoarding is also linked to seeking support from objects. Studies concerning
      attachment and hoarding suggest that attachment representations may impact
      seeking or possessing objects. Acquiring objects may give people momentary
      support, normally provided by the attachment figure in cases of stress. This
      study aims to better understand the links between attachment and hoarding. One
      hundred and ninety-seven non-clinical women (M = 30.58) completed two self-report
      questionnaires on attachment and hoarding behaviors. The results show a link
      between insecure attachment (preoccupied and fearful) and hoarding. Preoccupied
      and fearful attachments are characterized by a fear of loss and abandonment.
      Possession and accumulation of objects in hoarding could help insecure people to
      deal with these fears. Therefore, insecure attachment appears to be a
      vulnerability factor in the development of hoarding behaviors.

PMID- 30278411
TI  - An in-situ gamma-ray spectrometer for the deep ocean.
AB  - A low resolution subsea gamma-ray spectrometer is developed for monitoring
      radioactivity in the deep ocean. The detection system provides quantitative
      results combining experimental and simulated data. The system is tested for
      pressures up to 456 105 Pa and is demonstrated in the deep sea South of Crete
      (Greece) at a depth of 2700 m. The minimum detectable activity for 214Bi
      considering a 7200 s measurement, was found 0.3 Bq/L due to the extremely low
      background contribution at high energies.

PMID- 30278412
TI  - Rhetorical and regulatory boundary-work: The case of medical cannabis policy
      making in Israel.
AB  - Recent studies have explored how professionals draw boundaries to reach workable
      solutions in conflictual and contested areas. Yet they neglected to explore the
      relationships and dynamics between how boundaries are demarcated in rhetoric and
      in policy. This article examines these relationships empirically through the case
      of medical cannabis (MC) policy-making in Israel. Drawing on interviews with key
      stakeholders in the MC policy field, formal policy documents, and observations of
      MC conferences, this article sheds light on the dynamics between rhetorical
      boundary-work and what we term regulatory boundary-work, namely setting rules and
      regulations to demarcate boundaries in actual practice. Results show how certain
      definitions of and rationales for a discursive separation between "medical" and
      "recreational" cannabis and between cannabis "medicalization" and "legalization"
      prevailed and were translated into formal policy, as well as how stakeholders'
      reactions to this boundary-work produced policy changes and the shifting of
      boundaries. Both rhetorical and regulatory boundary-works emerge as ongoing
      contested processes of negotiation, which are linked in a pattern of reciprocal
      influence. These processes are dominated by certain actors who have greater power
      to determine how and why specific boundaries should be drawn instead of others.

PMID- 30278413
TI  - Evaluation of a teacher-led, life-skills intervention for secondary school
      students in Uganda.
AB  - RATIONALE: Despite a recognised need for mental health and life skills promotion
      for young people in low- and middle-income countries (LMICs), the evidence base
      for accessible and effective interventions is limited. OBJECTIVES: The objectives
      of this study were to determine if a school-based, teacher-led, life skills
      focused, and manualised intervention was effective in increasing self-efficacy,
      reducing internalising problems, promoting prosocial behaviour, and developing a
      sense of connectedness among secondary school students in Uganda. METHOD: A
      cluster controlled, before-and-after study was employed in four schools, with one
      school acting as a wait-list control. In total, 620 students aged 13-18 completed
      baseline questionnaires, with 170 of those completing the same measures post
      intervention. Interviews were also completed with four teachers and four students
      who had finished the intervention. Teachers from the intervention schools
      completed three days of training on the life skills manual and subsequently
      delivered the programme over a school year. The manual, written by the lead
      researcher with support from local facilitators, incorporated 24 lessons plans
      designed to promote mental health and resilience, develop communication skills,
      and teach life skills for the present and future. Training sessions also provided
      guidance on pedagogical approaches required to deliver this type of content
      effectively. RESULTS: Analysis of Covariance (ANCOVA) demonstrated that the
      intervention group had a significant increase in general self-efficacy, F(1,167)
      = 20.10, p < .001, eta2 = 0.107, significant reductions in internalising problems
      (depression/anxiety-like symptoms), F(1,167) = 11.14, p = .001, eta2 = 0.063, and
      an increase in overall 'Connectedness' F(1,167) = 15.00, p < .001, eta2 = 0.082,
      when compared to the control group. Effect sizes for these variables were medium.
      There was an increase in prosocial attitudes/behaviour that did not reach
      significance after Bonferroni correction. CONCLUSIONS: Despite limitations,
      including sample size at post-intervention and lack of randomisation, the study
      demonstrated that it is possible to deliver an effective, school-based,
      culturally-appropriate life skills intervention, involving local facilitators in
      design, delivery, and evaluation.

PMID- 30278414
TI  - Factors influencing the fate of antibiotic resistance genes during thermochemical
      pretreatment and anaerobic digestion of pharmaceutical waste sludge.
AB  - The prevalence of antibiotic resistance genes (ARGs) in waste sludge, especially
      for the pharmaceutical waste sludge, presents great potential risks to human
      health. Although ARGs and factors affecting their spreading are of major
      importance for human health, the factors influencing the fate of ARGs during
      sludge treatment, especially for pharmaceutical sludge treatment are not yet well
      understood. In order to be able to minimize ARGs spreading, it is important to
      find what is influencing their spreading. Therefore, certain factors, such as the
      sludge characteristics, bacterial diversity and community composition, and mobile
      genetic elements (MGEs) during the advanced AD of pharmaceutical sludge with
      different pretreatments were studied, and their affinity with ARGs was elucidated
      by Spearman correlation analysis. Furthermore, multiple linear regression was
      introduced to evaluate the importance of the various factors. Results showed that
      59.7%-88.3% of the variations in individual ARGs and total ARGs can be explained
      by the corresponding factors. Bacterial diversity rather than specific bacterial
      community composition affected the fate of ARGs, whereas alkalinity was the most
      important factor on ARGs among all sludge characteristics investigated in this
      study. Besides, 66.4% of variation of total ARGs was driven by the changes of
      MGEs. Multiple linear regression models also reveal the collective effect of
      these factors on ARGs, and the contributions of each factor impact on ARGs. This
      study provides more comprehension about the factors impact on the fate of ARGs
      during pharmaceutical sludge treatment, and offers an approach to evaluate the
      importance of each factor, which method could be introduced for evaluation of
      factors influencing ARGs during other types of sludge or wastewater treatment.

PMID- 30278415
TI  - Impact of prenatal heavy metal exposure on newborn leucocyte telomere length: A
      birth-cohort study.
AB  - Arsenic, cadmium and lead are toxic environmental contaminants. They were shown
      to be associated with telomere length (TL) in adults. Although they can cross the
      placental barrier, the effect of prenatal exposure of these metals on newborn TL
      is unknown. The aim of this study was to examine whether prenatal exposure to
      heavy metals has an impact on newborn leucocyte TL. A birth-cohort study was
      conducted with 409 pregnant women and their newborns in Myanmar. During the first
      visit, face-to-face interviews were conducted, and maternal spot urine sampling
      was performed. Cord blood samples were collected during follow-up. Urinary heavy
      metal concentration was measured by ICP-MS and adjusted for creatinine. Relative
      TL was measured by quantitative real-time polymerase chain reaction. The extent
      of prenatal arsenic, cadmium and lead exposure and their associations with
      newborn leucocyte TL were assessed using multivariate linear regression. The
      median values of maternal urinary arsenic, cadmium, and lead concentrations were
      73.9, 0.9, and 1.8 MUg/g creatinine, respectively. Prenatal arsenic and cadmium
      exposure was significantly associated with newborn TL shortening (lowest vs
      highest quartile, coefficient = - 0.13, 95% CI: - 0.22, - 0.03, p = 0.002, and
      coefficient = - 0.17, 95% CI: - 0.27, - 0.07, p = 0.001, respectively), and the
      associations remained robust after adjusting for confounders. There was no
      significant association between prenatal lead exposure and newborn TL. The
      present study identified the effect of arsenic and cadmium exposure on TL
      shortening, even in utero exposure at a lower concentration.

PMID- 30278416
TI  - A process-based model for pentachlorophenol dissipation in a flooded paddy soil.
AB  - Process-based models have been widely used for predicting environmental fate of
      contaminants. Nevertheless, accurate modeling of pentachlorophenol (PCP)
      dissipation in soils at the millimeter-scale remains a challenge due to the
      scarcity of observation data and uncertainty associated with model assumptions
      and estimation of the model parameters. To provide quantitative analysis of PCP
      dissipation at the anaerobic/aerobic interface of a rhizobox experiment, this
      study implemented Bayesian parameter estimation for a process-based reactive
      chemical transport model. The model considered the main transport and
      transformation processes of chemicals including diffusion, sorption and
      degradation. The contributions of the processes to PCP dissipation were
      apportioned both in space and time. Using the maximum-a-posteriori (MAP)
      estimation of parameters, our model fitted the experimental data better compared
      with the previous work. Our results indicated that the most reactive zone for PCP
      dissipation occurred in the layer of 0-2.4 mm where degradation in solid phase
      dominated the PCP dissipation, while upward diffusion was the main mechanism for
      the reduction of PCP concentration in deeper layer (2.4-4.8 mm). By considering
      the coupled reactive transport of PCP and Cl-, the average degrees of PCP
      dechlorination in each layer were estimated from corresponding total
      concentrations of PCP and Cl-. The degrees of PCP dechlorination in the ponding
      water and the top layer of soil profile were highest, while 2,3,4,5- TeCP and
      3,4,5- TCP were identified as the main dechlorination products in the soil. This
      study demonstrated that combining Bayesian estimation with process-based reactive
      chemical transport model can provide more insights of PCP dissipation at the
      millimeter-scale. This approach can help to understand complex dissipation
      mechanisms for other contaminants.

PMID- 30278417
TI  - Air pollution-derived PM2.5 impairs mitochondrial function in healthy and chronic
      obstructive pulmonary diseased human bronchial epithelial cells.
AB  - In order to clarify whether the mitochondrial dysfunction is closely related to
      the cell homeostasis maintenance after particulate matter (PM2.5) exposure,
      oxidative, inflammatory, apoptotic and mitochondrial endpoints were carefully
      studied in human bronchial epithelial BEAS-2B, normal human bronchial epithelial
      (NHBE) and chronic obstructive pulmonary disease (COPD)-diseased human bronchial
      epithelial (DHBE) cells acutely or repeatedly exposed to air pollution-derived
      PM2.5. Some modifications of the mitochondrial morphology were observed within
      all these cell models repeatedly exposed to the highest dose of PM2.5. Dose- and
      exposure-dependent oxidative damages were reported in BEAS-2B, NHBE and
      particularly COPD-DHBE cells acutely or repeatedly exposed to PM2.5. Nuclear
      factor erythroid 2-p45 related factor 2 (NRF2) gene expression and binding
      activity, together with the mRNA levels of some NRF2 target genes, were directly
      related to the number of exposures for the lowest PM2.5 dose (i.e., 2 MUg/cm2),
      but, surprisingly, inversely related to the number of exposures for the highest
      dose (i.e., 10 MUg/cm2). There were dose- and exposure-dependent increases of
      both nuclear factor kappa-B (NF-kappaB) binding activity and NF-kappaB target
      cytokine secretion in BEAS-2B, NHBE and particularly COPD-DHBE cells exposed to
      PM2.5. Mitochondrial ROS production, membrane potential depolarization, oxidative
      phosphorylation, and ATP production were significantly altered in all the cell
      models repeatedly exposed to the highest dose of PM2.5. Collectively, our results
      indicate a cytosolic ROS overproduction, inducing oxidative damage and activating
      oxygen sensitive NRF2 and NF-kB signaling pathways for all the cell models
      acutely or repeatedly exposed to PM2.5. However, one of the important highlight
      of our findings is that the prolonged and repeated exposure in BEAS-2B, NHBE and
      in particular sensible COPD-DHBE cells further caused an oxidative boost able to
      partially inactivate the NRF2 signaling pathway and to critically impair
      mitochondrial redox homeostasis, thereby producing a persistent mitochondrial
      dysfunction and a lowering cell energy supply.

PMID- 30278418
TI  - Corrigendum to "Pharmacotherapy for amphetamine dependence: A systematic review"
      [Drug Alcohol Depend. 191 (2018) 309-337].

PMID- 30278419
TI  - Impairments in reversal learning following short access to cocaine self
      administration.
AB  - BACKGROUND: Cocaine use disorder is characterized by compulsive drug-seeking that
      persists long into abstinence. Work using rodent models of cocaine addiction has
      found evidence for reversal learning deficits 21 days after non-contingent
      cocaine administration and 60 days after self-administration. Here we sought to
      determine if a deficit in reversal learning is present 3-4 weeks after cessation
      of cocaine self-administration, when relapse to cocaine-seeking is robust.
      Conversely, we hypothesized that reversal learning training would protect against
      relapse, similar to other forms of environmental enrichment. METHODS: Male rats
      underwent short access (ShA, 2 h/10d) or long access (LgA, 1 h/7d then 6 h/10d)
      cocaine self-administration, followed by 21-29 days of abstinence. During
      abstinence, a subset of rats underwent training in a plus-maze that required an
      egocentric strategy to earn a sucrose reward. Following response acquisition and
      retention, the ability to reverse the spatial navigation strategy was tested.
      RESULTS: Total trials to criteria and total errors made did not differ between
      the groups during response acquisition, retention, or reversal. On the first
      reversal test, ShA rats performed better than LgA and control rats. ShA rats'
      performance worsened over time. There were no effects of cognitive training or
      length of cocaine access on context-primed relapse of cocaine-seeking.
      CONCLUSIONS: The present data indicate that perhaps LgA cocaine self
      administration does not produce adaptations to regions mediating context-primed
      relapse as it does for cocaine and cocaine-associated cue-induced reinstatement
      of drug-seeking. A time-dependent deficit in reversal learning was found only in
      ShA rats. Reversal learning training did not protect against cocaine relapse.

PMID- 30278420
TI  - Reuse of materials from a Sustainable Drainage System device: Health, Safety and
      Environment assessment for an end-of-life Pervious Pavement Structure.
AB  - Pervious pavement systems can have a life span of about 20years but, at end-of
      life, it becomes necessary to evaluate the state of the infrastructure to
      determine whether they pose a health and safety risk to workers during
      dismantling, and also determine potential reuse of the waste material generated.
      In this paper, we report of an investigation conducted to evaluate whether
      Pervious pavement systems are hazardous to human health at end-of-life and also
      to assess the mobility of the stormwater pollutants trapped in the system as a
      measure of their potential release to receiving systems such as water-bodies and
      groundwater systems. After decommissioning, the pervious pavement structure was
      sampled for analysis including Gas Chromatography, inductively coupled plasma
      spectroscopy and, leachate analysis. Results show that carcinogenic risks were
      significantly below the regulatory limit of 1*10-6 while, the hazard quotients
      and cumulative hazard indices were also below regulatory value of 1, based on
      United States Environmental Protection Agency standards. Furthermore, mean
      concentrations of benzene, toluene, ethylbenzene and xylene were significantly
      less than the UK soil guideline values. The results of the leachate analysis show
      that the metals of concern, Pb, Zn, Cr, Ni, Cd and Cu were all below the
      threshold for reuse applications such as irrigation purposes as they were all
      below the regulatory limits such as Food and Agriculture Organization and, United
      States Environmental Protection Agency standards. Finally, the evaluation of
      potential reuse and recycling purposes indicate that wastes generated from the
      dismantling of the PPS are within limits for recycling as aggregates for other
      civil engineering projects as per European Union standards. This has potential to
      enhance UK's drive to achieve the target of 70% level of construction &
      demolition waste recovery for reuse and recycling by the year 2020 as per
      European Union Water Framework Directive.

PMID- 30278421
TI  - Impact of the widespread pharmaceutical pollutant fluoxetine on behaviour and
      sperm traits in a freshwater fish.
AB  - Pharmaceutical pollutants are detected in aquatic habitats and wildlife tissues
      globally. One widespread contaminant of major concern is the antidepressant
      fluoxetine, which can affect behavioural and physiological processes in non
      target species. Despite this, effects of fluoxetine on wildlife behaviour have
      seldom been investigated across multiple fitness-related contexts, especially at
      environmentally realistic concentrations. Accordingly, we examined impacts of 35
      day fluoxetine exposure at two environmentally relevant concentrations (31 and
      374 ng/L) across a suite of fitness-related contexts in wild-caught male
      mosquitofish (Gambusia holbrooki). First, we investigated anxiety-related
      behaviours (boldness, exploration and activity) in a novel environment (maze
      arena) and found no significant impacts of exposure. Second, we tested effects of
      fluoxetine in a reproductive context, including mating behaviour and sperm
      quality. We found that, relative to controls, fluoxetine exposure resulted in
      males spending a greater amount of time pursuing females. Further, low-exposed
      males were more likely to attempt copulation than unexposed males. Lastly, we
      investigated across-context behavioural correlations, and how fluoxetine exposure
      might affect such relationships. A significant positive correlation was detected
      in control fish between activity levels in the maze and time spent pursuing
      females in the reproductive assay. This relationship was disrupted by fluoxetine
      at both exposure levels. This is the first evidence that field-detected
      concentrations of a pharmaceutical pollutant can disturb across-context
      behavioural correlations in wildlife. Our findings provide clear evidence that
      fluoxetine can produce context-specific behavioural effects in fish and
      underscore how pharmaceutical exposure at field-detected concentrations can
      induce important shifts in wildlife behaviour.

PMID- 30278422
TI  - Use of integrated biomarker indexes for assessing the impact of receiving waters
      on a native neotropical teleost fish.
AB  - In the field of aquatic ecotoxicology, indexes obtained from a battery of
      biomarkers have proved to be a useful tool for assessing quantifiable and
      integrated health responses of organisms exposed to pollutants. The objective of
      this work was to evaluate the effects of exposure to the Reconquista River water
      (RR) on adults of Cnesterodon decemmaculatus using different integrated indexes.
      We conducted a 12-d laboratory assay involving the exposure of fish to RR, a
      negative control (moderately hard water - MHW medium), and a positive control
      (for genotoxicity with MHW + Cyclophosphamide, CP). There were measured metabolic
      (food intake and specific assimilation, specific metabolic rate, oxygen
      extraction efficiency, ammonia excretion, and ammonia quotient), genotoxic (comet
      assay, micronucleus test, and nuclear abnormalities), morphological variables
      (total length, body and liver weight) and biochemical variables (Electron
      Transport System - ETS, Acetylcholinesterase activity - AChE, Catalase - CAT,
      Glutathione-S-transferase - GST, Glutathione content - GSH and tissue proteins).
      These variables were grouped into different indexes: morphological (Condition
      Factor - K and Liver Somatic Index-LSI), metabolic (Scope for Growth-SFG),
      genetic damage (GDI) and integrated biomarker response - IBR (AChE brain, CAT,
      GST and GSH liver, GSH gills, ETS muscle) indexes. Results indicated that RR
      water induced metabolic, biochemical and genetic damages. The SFG, GDI and IBR
      were suitable to assess the effects of exposure to an environmental sample in an
      integrated approach, reducing uncertainty due to inherent biomarker variability.
      These indexes have emerged as promising tools for environmental monitoring
      studies.

PMID- 30278423
TI  - Overdose fertilization induced ammonia-oxidizing archaea producing nitrous oxide
      in intensive vegetable fields.
AB  - Little is known about the effects of nitrogen (N) fertilization rates on ammonia
      oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) and their
      differential contribution to nitrous oxide (N2O) production, particularly in
      greenhouse based high N input vegetable soils. Six N treatments (N1, N2, N3, N4,
      N5 and N6 representing 0, 293, 587, 880, 1173 and 1760 kg N ha-1 yr-1,
      respectively) were continuously managed for three years in a typically
      intensified vegetable field in China. The aerobic incubation experiment involving
      these field-treated soils was designed to evaluate the relative contributions of
      AOA and AOB to N2O production by using acetylene or 1-octyne as inhibitors. The
      results showed that the soil pH and net nitrification rate gradually declined
      with increasing the fertilizer N application rates. The AOA were responsible for
      44-71% of the N2O production with negligible N2O from AOB in urea unamended
      control soils. With urea amendment, the AOA were responsible for 48-53% of the
      N2O production in the excessively fertilized soils, namely the N5-N6 soils, while
      the AOB were responsible for 42-55% in the conventionally fertilized soils,
      namely the N1-N4 soils. Results indicated that overdose fertilization induced
      higher AOA-dependent N2O production than AOB, whereas urea supply led to higher
      AOB-dependent N2O production than AOA in conventionally fertilized soils.
      Additionally, a positive relationship existed between N2O production and NO2-
      accumulation during the incubation. Further mechanisms for NO2--dependent N2O
      production in intensive vegetable soils therefore deserve urgent attention.

PMID- 30278424
TI  - Spatially-explicit estimate of soil nitrogen stock and its implication for land
      model across Tibetan alpine permafrost region.
AB  - Permafrost soils store a large amount of nitrogen (N) which could be activated
      under the continuous climate warming. However, compared with carbon (C) stock,
      little is known about the size and spatial distribution of permafrost N stock. By
      combining measurements from 519 pedons with two machine learning models
      (supporting vector machine (SVM) and random forest (RF)), we estimated the size
      and spatial distribution of N stock across the Tibetan alpine permafrost region.
      We then compared these spatially-explicit N estimates with simulated N stocks
      from the Community Land Model (CLM). We found that N density (N amount per area)
      in the top three meters was 1.58 kg N m-2 (interquartile range: 1.40-1.76) across
      the study area, constituting a total of 1802 Tg N (interquartile range: 1605
      2008), decreasing from the southeast to the northwest of the plateau. N stored
      below 1 m accounted for 48% of the total N stock in the top three meters. CLM4.5
      significantly underestimated the N stock on the Tibetan Plateau, primarily in
      areas with arid/semi-arid climate. The process of biological N fixation played a
      key role in the underestimation of N stock prediction. Overall, our study
      highlights that it is imperative to improve the simulation of N processes and
      permafrost N stocks in land models to better predict ecological consequences
      induced by rapid and widespread permafrost degradation.

PMID- 30278425
TI  - The exposure of slums to high temperature: Morphology-based local scale thermal
      patterns.
AB  - Heat exposure has become a global threat to human health and life with increasing
      temperatures and frequency of extreme heat events. Considering risk as a function
      of both heat vulnerability and hazard intensity, this study examines whether poor
      urban dwellers residing in slums are exposed to higher temperature, adding to
      their vulnerable demographic and health conditions. Instead of being restricted
      by sampling size of pixels or other land surface zones, this study follows the
      intrinsic latent patterns of the heat phenomenon to examine the association
      between small clusters of slums and heat patterns. Remotely sensed land surface
      temperature (LST) datasets of moderate resolution are employed to derive the
      morphological features of the temperature patterns in the city of Ahmedabad,
      India at the local scale. The optimal representations of temperature pattern
      morphology are learnt automatically from temporally adjacent images without
      manually choosing model hyper-parameters. The morphological features are then
      evaluated to identify the local scale temperature pattern at slum locations.
      Results show that in particular locations with slums are exposed to a locally
      high temperature. More specifically, larger slums tend to be exposed to a more
      intense locally high temperature compared to smaller slums. Due to the small size
      of slums in Ahmedabad, it is hard to conclude whether slums are impacting the
      locally high temperature, or slums are more likely to be located in poorly built
      places already with a locally high temperature. This study complements the
      missing dimension of hazard investigation to heat-related risk analysis of slums.
      The study developed a workflow of exploring the temperature patterns at the local
      scale and examination of heat exposure of slums. It extends the conventional city
      scale urban temperature analysis into local scales and introduces morphological
      measurements as new parameters to quantify temperature patterns at a more
      detailed level.

PMID- 30278426
TI  - SCJ osteoarthritis: The significance of joint surface location for diagnosis.
AB  - An evaluation of the method used to diagnose sternoclavicular joint (SCJ)
      osteoarthritis (OA) in skeletal remains is presented, with particular attention
      given to the anatomy of the joint. The current palaeopathological diagnostic
      criteria used to identify SCJ OA were found to be appropriate for both the
      sternal and clavicular surfaces of the SCJ, with eburnation indicating
      perforation of the intra-articular disc and advanced disease. Eburnation was
      found to occur rarely in the SCJ, and if used as the sole diagnostic criterion
      would result in an underestimation of SCJ OA prevalence in archaeological
      assemblages. A key finding was the identification of changes characteristic of OA
      but confined to the attachment zone of the intra-articular disc on the clavicular
      surface of the SCJ. As this area of the joint is non-articular, and not normally
      covered with articular cartilage, a diagnosis of OA would be inaccurate and
      instead it should be considered as an enthesopathy. It is likely that SCJ OA has
      been incorrectly identified and over-diagnosed in the archaeological record in
      the past. More histological research into the disc attachment and its
      degeneration is required before this can be confirmed.

PMID- 30278427
TI  - Influence of polyphenolic content on the in vitro allergenicity of old and new
      apple cultivars: A pilot study.
AB  - OBJECTIVES: More than 70% of birch pollen-allergic individuals are affected by a
      cross-allergy from apples. The aim of this study was to determine if an increased
      polyphenolic content of apples is inversely related to clinical allergic
      reactions in sufferers. METHODS: The polyphenolic content of two old and two new
      apple cultivars was analyzed using high performance liquid chromatography. The in
      vitro concentration of sulfidoleukotrienes and the CD63 basophil activation of 27
      birch pollen sufferers with cross-reactivity to apples were determined with
      cellular antigen stimulation and basophil activation tests after incubation with
      different apple cultivars. RESULTS: The flesh of old cultivars was characterized
      by significantly higher total polyphenolic content (86.1 +/- 5.5 ug/g) than that
      of new cultivars (24.7 +/- 7.2 ug/g). The concentration of sulfidoleukotrienes
      and the CD63 basophil activation of old apple cultivars was up to 62% lower than
      new ones and decreased as the degree of enzymatic browning increased. CONCLUSION:
      Old apples cultivars are better tolerated than new ones by birch pollen-allergic
      individuals. The in vitro allergenicity (activation of effector cells) of apples
      depends on the total polyphenolic content and the degree of enzymatic browning.

PMID- 30278428
TI  - Impact of the preoperative use of synbiotics in colorectal cancer patients: A
      prospective, randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVES: Gastrointestinal microflora is involved in the development and
      regulation of the immune response. Non-pathogenic bacteria are important to
      prevent the development and subsequent invasion of enteropathogenic bacteria.
      Surgical trauma and intestinal preparation can disrupt the intestinal microbiota
      balance. Modulating the microbiota in the preoperative period in patients with
      colorectal cancer may have an effect on the occurrence of postoperative
      complications. The aim of this study was to assess the effect of preoperative
      synbiotic administration in patients with colorectal cancer subjected to
      colorectal resection. METHODS: This was a prospective, randomized, double-blind,
      placebo-controlled study of 73 patients with colorectal cancer. Eight days before
      surgery, patients were randomized to receive either synbiotics (Simbioflora,
      Farmoquimica, Sao Paulo, Brazi) or placebo (maltodextrin). The envelopes were
      identical and labeled A or B. All patients underwent nutritional assessment and
      measurements of C-reactive protein (CRP), interleukin (IL)-6, serum albumin, and
      transferrin. Patients were given a diluted envelope in 100mL of water twice daily
      for 7 d. The occurrence of infectious or non-infectious complications, time of
      antibiotic use, duration of hospitalization, and occurrence of deaths were
      recorded for 30 d postoperatively. RESULTS: Mean age, demographic data, and tumor
      staging were similar between the groups at baseline. After 7 d of synbiotic
      intake, there were significant reductions in IL-6 levels (163.2 +/- 19.5 versus
      138.8 +/- 12.5, P < 0.001) and CRP (10 +/- 5.2 versus 7.17 +/- 3.2, P < 0.001),
      whereas the control group did not present significant changes I IL-6 levels
      (154.2 +/- 18.3 versus 160.9 +/- 18.6, NS) or CRP (10.6 +/- 6.18 versus 10.4 +/-
      6.1, NS). Serum albumin and transferrin did not show significant changes.
      Postoperative infectious complications occurred in 2.8% of patients in the
      synbiotic group and in 18.9% of the control group (P = 0.02). The mean antibiotic
      usage time was 1.42 +/- 0.5 d in the synbiotic group and 3.74 +/- 4.3 d in the
      control group (P < 0.001). The mean hospital length of stay was 3 +/- 1 d in the
      synbiotic group and 4 +/- 18 in the control group (P < 0.001). Three deaths were
      reported in the control group and none in the synbiotic group (P = 0.115).
      CONCLUSIONS: The use of synbiotics for 7 d preoperatively in patients with
      colorectal cancer attenuates the inflammatory state and is associated with
      reductions in morbidity, hospital length of stay, and use of antibiotics.

PMID- 30278429
TI  - Effect of alpha-linolenic acid in combination with the flavonol quercetin on
      markers of cardiovascular disease risk in healthy, non-obese adults: A
      randomized, double-blinded placebo-controlled crossover trial.
AB  - OBJECTIVES: Alpha-linolenic acid (ALA) and quercetin are characteristic compounds
      in plant-based diets. Cardioprotective effects have been described for both
      substances, although a possible benefit of combining ALA and quercetin has not,
      to our knowledge, been evaluated yet. The aim of this study was to investigate
      the potential independent and additive effects of ALA and quercetin on blood
      pressure (BP) and lipid and glucose metabolism, as well as on biomarkers of
      inflammation, oxidative stress, and antioxidant status in healthy, non-obese men
      and women. Another aim was to examine whether chronic supplementation of
      supranutritional doses of quercetin would result in an accumulation of plasma
      quercetin concentration over time. METHODS: In a double-blinded, placebo
      controlled crossover trial, healthy volunteers were randomized to receive 3.6g/d
      ALA plus 190mg/d quercetin or placebo for 8 wk. Data from 67 individuals (34 men,
      33 women, mean age: 24.6 y) were assessed. RESULTS: Plasma quercetin,
      tamarixetin, isorhamnetin, and kaempferol increased significantly from baseline
      to study end with ALA + quercetin but not with ALA + placebo. No significant
      effect on office systolic BP, mean 24 h ambulatory BP (ABP), or mean daytime ABP
      was seen in either study group. Both interventions significantly decreased total
      cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein
      cholesterol, and apolipoprotein B to a similar extent. No effect on high-density
      lipoprotein cholesterol, apolipoprotein A1, glucose, uric acid, oxidized low
      density lipoprotein, C-reactive protein, or lipid-adjusted retinol, alpha
      tocopherol, or beta-carotene was seen in either group. CONCLUSION: Although
      dietary supplements of 3.6g/d ALA over an 8-wk period improved lipid profiles in
      healthy adults, antioxidative and oxidative status, inflammation, and BP remained
      unchanged. No evidence was seen for an additive or synergistic effect of ALA plus
      quercetin on markers of cardiovascular disease risk.

PMID- 30278430
TI  - Effect of resveratrol supplementation on lipid profile in subjects with
      dyslipidemia: A randomized double-blind, placebo-controlled trial.
AB  - OBJECTIVES: The aim of this study was to explore the effect of resveratrol
      supplementation on lipid profile in individuals with dyslipidemia. METHODS:
      Apparently healthy men and non-pregnant women 20 to 65 y of age with new
      diagnosis of dyslipidemia were enrolled in a randomized double-blind, placebo
      controlled trial and randomly allocated to receive either resveratrol 100mg/d or
      placebo (sucrose 0.5 g/d) for 2 mo. Smoking, alcohol intake, diabetes, acute or
      chronic renal or hepatic diseases, malignancy, cardiovascular disease, serum
      triacylglycerol levels >=400mg/dL, low-density lipoprotein cholesterol levels
      >=190mg/dL, and consumption of lipid-lowering drugs or supplements containing
      resveratrol were exclusion criteria. RESULTS: Seventy-one individuals with new
      diagnosis of dyslipidemia were enrolled and randomly allocated to the resveratrol
      (n = 35) or placebo groups (n = 36). At baseline, there were no significant
      differences between the study groups. After intervention period, individuals in
      the resveratrol group showed a significant decrease in total cholesterol (201.4
      +/- 34.4 versus 220.6 +/- 37.4, P = 0.04) and triacylglycerol (133.4 +/- 55.3
      versus 166.7 +/- 68.5, P = 0.04) concentrations compared with the placebo group,
      without significant statistical differences for high-density lipoprotein
      cholesterol and low-density lipoprotein cholesterol levels. CONCLUSION: The
      results suggest that resveratrol supplementation significantly reduces total
      cholesterol and triacylglycerol concentrations in individuals with dyslipidemia.

PMID- 30278431
TI  - Faculty perspectives on the use of standardized versus non-standardized oral
      examinations to assess medical students.
AB  - Objectives: To determine if faculty perceive standardized oral examinations to be
      more objective and useful than the non-standardized format in assessing third
      year medical students' learning on the obstetrics and gynecology rotation.
      Methods: Obstetrics and gynecology faculty at three teaching hospitals were
      sampled to complete a survey retrospectively comparing the standardized oral
      examination (SOE) and non-standardized or traditional oral examinations (TOE).  A
      Likert scale (0-5) was used to assess satisfaction, objectivity, and usefulness
      of SOE and TOE.  Wilcoxon signed rank test was performed to compare median Likert
      scale scores for each survey item. A Spearman's correlation coefficient was used
      to investigate the relationship between the perceived level of objectivity and
      SOE characteristics. For qualitative measures, content analysis was applied.
      Results: Sixty-six percent (n=25) of eligible faculty completed the survey.
      Faculty perceived the standardized oral examination as significantly more
      objective compared with the non-standardized (z=-3.15, p=0.002). Faculty also
      found SOE to be more useful in assessing overall clerkship performance (z=-2.0,
      p<0.05). All of the survey participants were willing to administer the
      standardized examination again.  Faculty reported strengths of the SOE to be
      uniformity, fairness, and ease of use. Major weaknesses reported included
      inflexibility and decreased ability to assess students' higher order reasoning
      skills. Conclusions: Faculty found standardized oral examinations to be more
      objective in assessing third-year medical students' clinical competency when
      compared with a non-standardized approach.  This finding can be meaningfully
      applied to medical education programs internationally.

PMID- 30278432
TI  - Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co
      Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors.
AB  - BACKGROUND/AIMS: Multidrug resistance (MDR) is the most common cause of
      chemotherapy failure. Upregulation of P-glycoprotein (P-gp) is one of the main
      mechanisms underlying MDR. METHODS: In this study, we developed a targeted drug
      and small interfering (si)RNA co-delivery system based on specific aptamer
      conjugated grapefruit-derived nanovectors (GNVs) that we tested in MDR LoVo colon
      cancer cells. The internalization of nanovectors in cancer cells was tested by
      fluorescence microscopy and flow cytometry. The anti-cancer activity in vitro was
      determined by colony formation and cell apoptosis assays. The biodistribution of
      nanovectors was analyzed by live imaging and the anti-cancer activity in vivo was
      observed. RESULTS: GNVs loaded with aptamer increased doxorubicin (Dox)
      accumulation in MDR LoVo cells, an effect that was abolished by pretreatment with
      DNase. The LA1 aptamer effectively promoted nanovector internalization into cells
      at 4 degrees C and increased the targeted delivery of Dox to tumors. Constructs
      harboring Dox, LA1, and P-gp siRNA more effectively inhibited proliferation and
      enhanced apoptosis in cultured MDR LoVo cells while exhibiting more potent anti
      tumor activity in vivo than free Dox or GNVs loaded with Dox alone or in
      conjunction with LA1, an effect that was associated with downregulation of P-gp
      expression. CONCLUSION: This GNV-based system may be an effective strategy for
      overcoming MDR in clinical settings.

PMID- 30278433
TI  - Circular RNA Expression Profile and Analysis of Their Potential Function in
      Psoriasis.
AB  - BACKGROUND/AIMS: Circular RNAs (circRNAs) are evolutionary conserved circular non
      coding RNAs that play a role in several diseases by sequestering (sponging)
      microRNAs (miRNAs). However, their role in psoriasis remains unclear. In the
      present study, we investigated the expression of circRNAs and analyzed their
      potential functions in psoriasis. METHODS: The SBC human ceRNA array V1.0 was
      used to analyze circRNA expression in psoriatic lesions and normal healthy skin
      tissues. Functional analyses were performed using Gene ontology (GO) and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Putative miRNA
      response elements (MREs) were identified using miRNA target prediction software.
      Six upregulated circRNAs were verified by quantitative real-time reverse
      transcription polymerase chain reaction in psoriatic lesions and healthy skin
      tissues. RESULTS: A total of 4956 circRNAs (3016 upregulated and 1940
      downregulated; fold change >=2 and p< 0.05) were identified as differentially
      expressed in psoriasis. Furthermore, 4405 MREs were identified among the
      differentially expressed circRNAs. hsa_circ_0061012 was upregulated in psoriatic
      lesions compared with normal healthy skin tissues. The top five MREs of
      hsa_circ_0061012 were hsa-miR-7157-5p, hsa-miR-4769-3p, hsa-miR-6817-5p, hsa-miR
      4310, and hsa-miR-6882-3p. GO analysis was carried out to investigate the
      biological functions enriched among the upregulated targets of five miRNAs in
      psoriasis. The GO analysis identified that most of top 30 of GO enrichment are
      related to psoriasis. CONCLUSION: hsa_circ_0061012 might be a candidate biomarker
      for psoriasis. The results provide a new perspective for a better understanding
      of ceRNA-mediated gene regulation in psoriasis, and provide a novel theoretical
      basis for further studies on the function of circRNA in psoriasis.

PMID- 30278434
TI  - Micropapular Cutaneous Sarcoidosis Reviewed.
AB  - BACKGROUND: Micropapular cutaneous sarcoidosis (MPCS) is a rare variant of
      sarcoidosis. Herein we review the literature and include a recent case of MPCS
      discussing pathogenesis, diagnosis, treatment, and prognosis. METHOD: A review
      was conducted using the terms "micropapular sarcoidosis" and "micropapular
      sarcoid." A recent case of a 50-year-old male patient with biopsy-identified MPCS
      was also included in the review. RESULTS: In total, 12 cases with an aggregate of
      18 patients were included in the review. Presentation among all patients was
      consistent, with scattered, occasionally pruritic, faintly erythematous shiny
      white papules. Skin biopsy demonstrated noncaseating granulomas. Systemic
      prednisone, oxytetracycline, and hydroxychloroquine, as well as topical
      betamethasone, were used for therapy. CONCLUSION: In our review there does not
      seem to be a clear link as to the definite cause of the MPCS. While the
      relationships to tuberculosis and autoimmunity seem to be often emphasized, there
      was no clear association with either etiology.

PMID- 30278435
TI  - Liver Maximum Capacity: A Novel Test to Accurately Diagnose Different Stages of
      Liver Fibrosis.
AB  - AIM: To assess the diagnostic accuracy of liver maximum capacity (LiMAx(r)) test
      compared to transient elastography (TE) and serum biomarkers for the noninvasive
      detection of different stages of liver fibrosis and cirrhosis. PATIENTS AND
      METHODS: We retrospectively correlated LiMAx(r), TE, aspartate aminotransferase
      (AST) to alanine aminotransferase (ALT) ratio (AAR), AST-to-platelet ratio index
      (APRI), and fibrosis-4 (FIB-4) score with histological specimens in 102 patients
      with chronic liver disease (CLD) who underwent liver biopsy (either
      percutaneously or via mini-laparoscopy) at the University Clinic of Essen between
      10/2016 and 12/2017. RESULTS: Median LiMAx(r) values showed a tendency to
      decrease in accordance with increasing histological degree of fibrosis based on
      the Desmet scoring system (F0: 446.5 [381.0-592.5] ug/h/kg, F1: 405.0 [343.0
      547.0] ug/h/kg, F2: 337.0 [250.0-394.0] ug/h/kg, F3: 281.0 [262.0-364.0] ug/h/kg,
      and F4: 181.5 [130.0-256.5] ug/h/kg. Furthermore, -LiMAx(r) was superior to TE,
      FIB-4, AAR, and APRI in detecting different stages of fibrosis, while Spearman's
      rank correlation test showed a statistically significant association of -0.68,
      0.62, 0.61, 0.46, and 0.42, respectively. However, the combination of TE and
      LiMAx(r) had the highest diagnostic accuracy in detecting liver cirrhosis
      (sensitivity 88.9%, specificity 84.6%, Youden index 0.735). CONCLUSION: Enzymatic
      liver function measured by LiMAx(r) showed strong correlation with histology in
      patients with CLD irrespective of its underlying etiology and was superior to TE
      and serum biomarkers, possibly making it useful as a novel and noninvasive tool
      for the determination of hepatic disease severity.

PMID- 30278436
TI  - Laitinen's Subgenual Cingulotomy: Anatomical Location and Case Report.
AB  - BACKGROUND: The widespread use of deep brain stimulation (DBS) for movement
      disorders has renewed the interest in DBS for psychiatric disorders. Lauri
      Laitinen was a pioneer of stereotactic psychosurgery in the 1950s to 1970s,
      especially by introducing the subgenual cingulotomy. Our aim here was to verify
      the anatomical target used by Laitinen, to report on a patient who underwent this
      procedure, and to review the literature. MATERIALS AND METHODS: The records of
      Helsinki University Hospital were searched for psychosurgical cases performed
      between 1970 and 1974. Alive consenting patients were interviewed and underwent a
      brain MRI. RESULTS: We found 1 patient alive who underwent subgenual cingulotomy
      in 1971 for obsessive thoughts, anxiety, and compulsions, diagnosed at that time
      as "schizophrenia psychoneurotica." MRI showed bilateral subgenual cingulotomy
      lesions (254 and 160 mm3, respectively). The coordinates of the center of the
      lesions in relation to the midcommissural point for the right and left,
      respectively, were: 7.1 and 7.9 mm lateral; 0.2 mm inferior and 1.4 mm superior,
      and 33.0 and 33.9 anterior, confirming correct subgenual targeting. The patient
      reported retrospective satisfactory results. CONCLUSIONS: The lesion in this
      patient was found to be in the expected location, which gives some verification
      of the correct placement of Laitinen's subgenus cingulotomy target.

PMID- 30278437
TI  - Validity of Laparoscopic Gastrectomy in the Elderly.
AB  - OBJECTIVES: This study aimed to investigate the validity of laparoscopic gastric
      cancer surgery in elderly patients. METHODS: A total of 202 patients who
      underwent laparoscopic gastrectomy for gastric cancer between January 2007 and
      December 2016 were divided into an elderly group (age >=75 years, n = 36) and a
      control group (age < 75 years, n = 166). The patients' clinicopathological data
      were reviewed. RESULTS: The overall morbidity rate was relatively higher in the
      elderly group (16.7 vs. 11.4%, p = 0.389), whereas the incidence of serious
      complications >=grade III according to the Clavien-Dindo classification did not
      increase significantly in the elderly group (8.3 vs. 7.8%, p = 0.920). Univariate
      and multivariate analyses revealed that age >=75 years was not a significant
      predictive factor of postoperative morbidity (p = 0.568). There was no
      significant difference in the 5-year overall survival rate of patients with
      pathological stage I gastric cancer between the groups (97.1 vs. 96.1%, p =
      0.704; hazard ratio, 0.669; 95% confidence interval, 0.036-3.692). CONCLUSIONS:
      Laparoscopic gastrectomy has an acceptable morbidity rate in elderly patients,
      and the long-term outcome of patients with stage I gastric cancer was similar to
      that of the control group.

PMID- 30278438
TI  - Association of Environmental Tobacco Smoke with the Risk of Severe Early
      Childhood Caries among 3-Year-Old Japanese Children.
AB  - Severe early childhood caries (S-ECC) has serious consequences for primary
      dentition, affecting the overall health, well-being, and quality of life of the
      child. The aim of this study was to investigate the association of risk factors,
      including environmental tobacco smoke (ETS), with S-ECC in 3-year-old Japanese
      children by a cross-sectional study. Study subjects were 2,825 children aged 3
      years old. Of these individuals, after excluding the study subjects with missing
      values, a total of 2,277 children were included in the present analysis. The self
      administered questionnaire included such items as sex, whether a smoker resides
      in the home, the number of smokers in the home, snack time, drinking or eating
      sweets after dinner, frequency of parents brushing their child's teeth, the use
      of fluoride toothpaste, and socioeconomic status. We obtained the number of
      decayed, missing, or filled teeth per person (dmft) from dental examinations.
      Logistic regression analysis was performed to estimate the odds ratio for S-ECC.
      The average number of decayed, missing, and filled teeth (dmft index) was 0.77.
      The prevalence of dental caries was 20.6%. There was at least 1 smoker in the
      homes of 1,370 subjects (60.2%). After excluding items of multicollinearity, the
      results of multivariate analysis were as follows: drinking or eating sweets after
      dinner, irregular snack times, parents brushing their child's teeth less
      frequently, existence of smokers in the home, and no residence tax were
      significantly associated with S-ECC. This study suggests that there is a
      significant association between ETS from family members and S-ECC.

PMID- 30278439
TI  - lncRNA AFAP1-AS1 Promotes Migration and Invasion of Non-Small Cell Lung Cancer
      via Up-Regulating IRF7 and the RIG-I-Like Receptor Signaling Pathway.
AB  - BACKGROUND/AIMS: Accumulating evidence has highlighted the importance of long non
      coding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in tumor biology.
      Among others, actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has
      been associated with non-small cell lung cancer (NSCLC). However, it remains
      unclear how AFAP1-AS1 participates in the development and progression of NSCLC.
      METHODS: The peripheral blood samples were collected from patients with NSCLC.
      White blood cell subsets were classified and levels of interleukin (IL)-10, IL-12
      and IFN-gamma in serum were measured. We then identified its target gene of AFAP1
      AS1 via bioinformatics methods. NSCLC cell line with the highest expression of
      AFAP1-AS1, i.e. H1975 was selected for in vitro experiments. A series of
      inhibitor, vector and siRNA were employed to validate the regulatory mechanisms
      of AFAP1-AS1 in the development and progression of NSCLC. Cell proliferation was
      detected by MTT assay and EdU staining. Cell migration and invasion, and cell
      cycle and apoptosis were measured by transwell assay and flow cytometry,
      respectively. RESULTS: A high expression of AFAP1-AS1 was identified in NSCLC,
      alongside with a reduced level of IL-12 and increased levels of IL-10 and
      interferon (IFN)-gamma. Aberrant expressions of AFAP1-AS1 were associated with
      pathological grade, TNM staging and metastatic potential of NSCLC. AFAP1-AS1
      could activate interferon regulatory factor (IRF)7, the retinoid-inducible
      protein (RIG)-I-like receptor signaling pathway and Bcl-2 in vitro. Over
      expression of AFAP1-AS1 promoted NSCLC cell proliferation, invasion and migration
      while inhibiting cell apoptosis. CONCLUSION: lncRNA AFAP1-AS1 promotes migration
      and invasion of non-small cell lung cancer via up-regulating IRF7 and the RIG-I
      like receptor signaling pathway.

PMID- 30278441
TI  - Mission Statement.

PMID- 30278440
TI  - Diet and Lifestyle Role in Homocysteine Metabolism in Turner's Syndrome.
AB  - OBJECTIVE: Patients with Turner syndrome (TS) have an unfavorable cardiometabolic
      profile. Hyperhomocysteinemia is a potential cardiovascular risk factor
      influenced by genetic and environmental factors, therapies, unbalanced diets and
      other lifestyle factors. We retrospectively studied the relationship between
      total plasma homocysteine (Hcy), serum vitamin B12 (B12) and folate concentration
      (s-F) in TS patients, taking into account the genetic profile, diet, smoking
      habits, hormonal therapies and dietary supplements of the subjects. PATIENTS AND
      METHODS: We evaluated 50 TS patients (31.5 ? 12.5yrs). Medication, including
      vitamin supplementation, was obtained. Eating habits, cigarette smoking, alcohol
      and coffee consumption were investigated using phone interviews. Levels of Hcy
      metabolism parameters were classified by using the relevant cut-off value for an
      adult population and compared with a reference sample drawn from the general
      population. RESULTS: Inadequate Hcy and B12 levels were noted, despite vitamin
      supplementation. Holotranscobalamin (HoloTC) was above the relevant cut-off in
      the population and supplemented subjects showed mean levels lower than non
      supplemented subjects (p = 0.005). Dietary supplementation (p = 0.038), lifestyle
      (coffee consumption p = 0.01) and hormonal replacement therapy (p = 0.02) are
      important factors for Hcy metabolism. No genetic influence on Hcy levels was
      noted. Multivariable regression analysis identified vitamin supplementation (p =
      0.045) as the only independent predictor of increased Hcy levels. CONCLUSION:
      Cardiovascular risk in Turner syndrome can be reduced using educational
      approaches to a healthy lifestyle with dietary guidelines. Besides this, we also
      recommend measuring HoloTC for the prompt detection of B12 deficiency and to
      consider hormone replacement therapy in the biochemical assessment of
      homocysteine in TS.

PMID- 30278443
TI  - Evaluation of an Intubation Readiness Score to Assess Neonatal Sedation before
      Intubation.
AB  - BACKGROUND: Premedication for neonatal intubation facilitates the procedure and
      reduces stress and physiological disturbances. However, no validated scoring
      system to assess the effect of premedication prior to intubation is available.
      OBJECTIVE: To evaluate the usefulness of an Intubation Readiness Score (IRS) to
      assess the effect of premedication prior to intubation in newborn infants.
      METHODS: Two-center prospective study in neonates who needed endotracheal
      intubation. Intubation was performed using a standardized procedure with propofol
      1-2 mg/kg as premedication. The level of sedation was assessed with the IRS by
      evaluating the motor response to a firm stimulus (1 = spontaneous movement; 2 =
      movement on slight touch; 3 = movement on firm stimulus; 4 = no movement).
      Intubation was proceeded if an adequate effect, defined as an IRS of 3 or 4, was
      reached. IRS was compared to the quality of intubation measured with the Viby
      Mogensen intubation score. RESULTS: A total of 115 patients, with a median
      gestational age of 27.7 weeks (interquartile range 5.3) and a median birth weight
      of 1,005 g (interquartile range 940), were included. An adequate IRS was achieved
      in 105 patients, 89 (85%) of whom also had a good Viby-Mogensen intubation score
      and 16 (15%) had an inadequate Viby-Mogensen intubation score. The positive
      predictive value of the IRS was 85%. CONCLUSIONS: Preintubation sedation
      assessment using the IRS can adequately predict optimal conditions during
      intubation in the majority of neonates. We suggest using the IRS in routine
      clinical care. Further research combining the IRS with other parameters could
      further improve the predictability of adequate sedation during intubation.

PMID- 30278444
TI  - Transanal Endoscopic Microsurgery or Total Mesorectal Excision: Not an Anagram!

PMID- 30278442
TI  - The Profile of Genetic Mutations in Papillary Thyroid Cancer Detected by Whole
      Exome Sequencing.
AB  - BACKGROUND/AIMS: The purpose of the study was to investigate the altered driver
      genes and signal pathways during progression of papillary thyroid cancer (PTC)
      via next-generation sequencing technology. METHODS: The DNA samples for whole
      exome sequencing (WES) analyses were extracted from 11 PTC tissues and adjacent
      normal tissues samples. Direct Sanger sequencing was applied to validate the
      identified mutations. RESULTS: Among the 11 pairs of tissues specimens, 299
      single nucleotide variants (SNVs) in 75 genes were identified. The most common
      pattern of base pair substitutions was T:A>C:G (49.83%), followed by C:G>T:A
      (18.06%) and C:G>G:C (15.05%). The altered genes were mainly implicated in MAPK
      (mitogen-activated protein kinase), PPAR (peroxisome proliferator-activated
      receptors), and p53 signaling pathways. In addition, 12 novel identified driver
      genes were validated by Sanger sequencing. The mutations of FAM133A, DPCR1, JAK1,
      C10orf10, EPB41L3, GPRASP1 and IWS1 exhibited in multiple PTC cases. Furthermore,
      the PTC cases exhibited individual mutational signature, even the same gene might
      present different mutational status in different cases. CONCLUSION: Multiple PTC
      related somatic mutations and signal pathways are identified via WES and Sanger
      sequencing methods. The novel identified mutations in genes such as FAM133A,
      DPCR1, and JAK1 may be potential therapeutic targets for PTC patients.

PMID- 30278445
TI  - Gq-Induced Apoptosis is Mediated by AKT Inhibition That Leads to PKC-Induced JNK
      Activation.
AB  - BACKGROUND/AIMS: Gq protein-coupled receptors (GqPCRs) regulate various cellular
      processes including mainly proliferation and differentiation. In a previous
      study, we found that in prostate cancer cells, the GqPCR of GnRH induces
      apoptosis by reducing the PKC-dependent AKT activity and elevating JNK
      phosphorylation. Since it was thought that GqPCR induces mainly activation of
      AKT, we undertook to examine how general is this phenomenon and understand its
      signaling. METHODS: We used various cells to follow the phosphorylation of
      signaling components using western blotting. RESULTS: In a screen of 21 cell
      lines, we found that PKC activation results in the reduction of AKT activity,
      which correlates nicely to JNK activation and in some cases to apoptosis. To
      further understand the signaling pathways involved in this stimulation, we
      studied in detail the SVOG-4O and alphaT3-1 cells. We found that PGF2alpha and
      GnRH agonist (GnRH-a) indeed induce significant Gq- and PKC- dependent apoptosis
      in these cells. This is mediated by two signaling branches downstream of PKC,
      which converge at the level of MLK3 upstream of JNK. One branch consists on c-Src
      activation of the JNK cascade and the second involves reduction of AKT activity
      that alleviates its inhibitory effect on MLK3, to allow the flow of the c-Src
      signal to JNK. At the MAPKK level, we found that the signal is transmitted by
      MKK7 and not MKK4. CONCLUSION: Our results present a general mechanism that
      mediates a GqPCR-induced, death receptors-independent, apoptosis in
      physiological, as well as cancer-related systems.

PMID- 30278446
TI  - Circular RNA Expression in the Brain of a Neonatal Rat Model of Periventricular
      White Matter Damage.
AB  - BACKGROUND/AIMS: Periventricular white matter damage (PWMD) is the predominant
      neurologic lesion in preterm infants who survive brain injury. In this study, we
      assessed the global changes in and characteristics of the transcriptome of
      circular RNAs (circRNAs) in the brain tissues of rats with PWMD. METHODS: We
      compared the expression profiles of circRNAs in brain samples from three rats
      with PWMD and three paired control tissues using deep RNA sequencing.
      Bioinformatics analysis was applied to investigate these differentially expressed
      circRNAs, and quantitative reverse-transcription polymerase chain reaction (qRT
      PCR) analysis was performed to confirm the results. Gene Ontology (GO) and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict
      associated cell signaling pathways and functions. Network analysis was performed
      to predict circRNAs-microRNAs, and target genes related to PWMD. RESULTS: A total
      of 2151 more reliable circRNAs were dysregulated in the brain tissues of rats
      with PWMD, indicating a potential role in the condition. Of the 98 circRNAs
      significantly differentially expressed in rat brains with PWMD (P< 0.05), 52 were
      significantly over-expressed and 46 were significantly under-expressed. The
      expression profiles of seven of 10 randomly selected circRNAs were confirmed by
      qRT-PCR analysis. The glutamatergic synapse pathway and the VEGF signaling
      pathway, both associated with hypoxia/ischemia induced brain damage, were
      inriched. Relationship between miRNA (rno-miR-433-3p and rno-miR-206-3p) and HIF
      1alpha were evident and potential associations between chr6: 48820833|48857932
      and their target genes (rno-miR-433-3p and rno-miR-206-3p) were identified.
      CONCLUSION: The distinct expression patterns of circRNAs in the brain tissues of
      rats with PWMD suggest that circRNAs actively respond to hypoxia-ischemia. These
      findings could assist the development of novel diagnostic and therapeutic targets
      for PWMD therapy.

PMID- 30278447
TI  - Characteristics of Lung Cancer in Patients Younger than 40 Years: A Prospective
      Multicenter Analysis in France.
AB  - OBJECTIVES: The aim of this study was to describe the demographic and clinico
      pathological characteristics of lung cancer in patients younger than 40 years.
      MATERIALS AND METHODS: This was a prospective study performed within the Groupe
      Francais de Pneumo-Cancerologie. Consecutive patients diagnosed with lung cancer
      before the age of 40 years were eligible. Data on demographics, medical history,
      clinico-pathological characteristics, treatment and overall survival were
      analysed. RESULTS: In total, 146 patients were included from January 2011 to
      December 2013. Median age was 38 years (IQR: 34-40). Women accounted for 41%.
      Main histological type was adenocarcinoma (77%). Only 3% had a prior history of
      cancer, but a family history (first- or second-degree relatives) of cancer was
      reported in 80 (55%) patients; 85 and 50% were current or past smokers of tobacco
      and cannabis, respectively; 82% had stage IIIB/IV at diagnosis. Median overall
      survival was 15.3 (95% CI: 8.1-24.0) months in the whole population, 10.3 (95%
      CI: 12.5-14.2) months in stage IV and 15 (95% CI: 8.7-35.2) months in stage III.
      One- and two-year overall survival rates were 57% (95 CI: 49-65) and 31.5% (95
      CI: 27-43), respectively. Compared to smokers, non-smokers were significantly
      younger and more often females. Median overall survival was not statistically
      different between smokers and non-smokers.

PMID- 30278448
TI  - Deletions in SERPING1 Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor
      Function Can Predict Disease Severity.
AB  - BACKGROUND: How genotype affects phenotype in hereditary angioedema with C1
      inhibitor deficiency (C1-INH-HAE) has not been totally clarified. In this study,
      we investigated the relationship between different types of mutations and various
      phenotypic characteristics. METHODS: Clinical data from 81 patients from 47
      families were recorded. Complement proteins were analyzed from 61 untreated
      patients. The coding exons and the exon-intron boundaries of the SERPING1 gene
      were sequenced, and deletion/duplication analysis with multiple ligation
      dependent probe amplification was performed. The relationship of complement
      protein with the mutation type was analyzed by using generalized estimating
      equations. RESULTS: Thirty-five different mutations (15 novel and 2/15
      homozygous) were identified. There was no causative mutation in 6 patients
      (7.4%). Patients with deletion and large deletion had the lowest (5.05%, 0-18.7;
      5.8%, 0-16.5%, respectively), and the none mutation group had the highest C1
      inhibitor function (23.3%, 11-78%, p < 0.001). C1 inhibitor function levels
      decreased as the age of the disease progressed (r = -0.352, p = 0.005). Lower C1
      inhibitor function levels caused severer disease (r = -0.404, p = 0.001) and more
      frequent annual attacks (r = -0.289, p = 0.024). In the off-attack period, C1q
      levels were lower than normal in 9.8% of the patients. CONCLUSION: Deletion
      mutations may represent the most unfavorable effect on C1 inhibitor function. The
      earlier disease onset age could be a sign for lower C1 inhibitor function levels
      in adult life. C1q levels could also be low in C1-INH-HAE patients, as in
      acquired angioedema. Lower C1 inhibitor function can predict disease severity and
      may have negative impacts on the course of C1-INH-HAE.

PMID- 30278449
TI  - miR-449a Suppresses Tamoxifen Resistance in Human Breast Cancer Cells by
      Targeting ADAM22.
AB  - BACKGROUND/AIMS: Most of estrogen receptor positive breast cancer patients
      respond well initially to endocrine therapies, but often develop resistance
      during treatment with selective estrogen receptor modulators (SERMs) such as
      tamoxifen. Altered expression and functions of microRNAs (miRNAs) have been
      reportedly associated with tamoxifen resistance. Thus, it is necessary to further
      elucidate the function and mechanism of miRNAs in tamoxifen resistance. METHODS:
      Tamoxifen sensitivity was validated by using Cell Counting Kit-8 in tamoxifen
      sensitive breast cancer cells (MCF-7, T47D) and tamoxifen-resistant cells (MCF
      7/TAM, T47D/ TAM). Quantitative real-time polymerase chain reaction (qRT-PCR) was
      performed to detect the expression level of miR-449a in tamoxifen-sensitive/
      resistant cells and patient serums. Dual-luciferase assay was used to identify
      the binding of miR-449a and predicted gene ADAM22. The expression level of ADAM22
      was determined by qRT-PCR and western blotting in miR-449a +/- breast cancer
      cells. Subsequently, rescue experiments were carried out to identify the function
      of ADAM22 in miR-449a-reduced tamoxifen resistance. Finally, Gene ontology (GO)
      and Protein-protein interaction analyses were performed to evaluate the potential
      mechanisms of ADAM22 in regulating tamoxifen resistance. RESULTS: MiR-449a levels
      were downregulated significantly in tamoxifen-resistant breast cancer cells when
      compared with their parental cells, as well as in clinical breast cancer serum
      samples. Overexpression of miR-449a re-sensitized the tamoxifen-resistant breast
      cancer cells, while inhibition of miR-449a conferred tamoxifen resistance in
      parental cells. Luciferase assay identified ADAM22 as a direct target gene of miR
      449a. Additionally, silencing of ADAM22 could reverse tamoxifen resistance
      induced by miR-449a inhibition in ER-positive breast cancer cells. GO analysis
      results showed ADAM22 was mainly enriched in the biological processes of cell
      adhesion, cell differentiation, gliogenesis and so on. Protein-protein
      interaction analyses appeared that ADAM22 might regulate tamoxifen resistance
      through PPARG, LGI1, KRAS and LYN. CONCLUSION: Decreased miR-449a causes the
      upregulation of ADAM22, which induces tamoxifen resistance of breast cancer
      cells. These results suggest that miR-449a, functioning by targeting ADAM22,
      contributes to the mechanisms underlying breast cancer endocrine resistance,
      which may provide a potential therapeutic strategy in ER-positive breast cancers.

PMID- 30278451
TI  - Thermal Response of Epigenetic Genes Informs Turtle Sex Determination with and
      without Sex Chromosomes.
AB  - Vertebrate sexual fate can be established by environmental cues (e.g.,
      temperature-dependent sex determination, TSD) or by genetic content (genotypic
      sex determination, GSD). While methylation is implicated in TSD, the influence of
      broader epigenetic processes in sexual development remains obscure. Here, we
      investigated for the first time the embryonic gonadal expression of the genome
      wide epigenetic machinery in turtles, including genes and noncoding RNAs (ncRNAs)
      involved in DNA/histone acetylation, methylation, ubiquitination,
      phosphorylation, and RNAi. This machinery was active and differentially
      thermosensitive in TSD versus GSD (ZZ/ZW) turtles. Methylation and histone
      acetylation genes responded the strongest. The results suggest these working
      hypotheses: (i) TSD might be mediated by epigenetically controlled hormonal
      pathways (via acetylation, methylation, and ncRNAs), or by (ii) hormonally
      controlled epigenetic processes, and (iii) key epigenetic events prior to the
      canonical thermosensitive period may explain differences between TSD and GSD.
      Novel epigenetic candidate regulators other than methylation were identified,
      including previously unknown ncRNAs that could potentially mediate gonadogenesis.
      These findings illuminate the molecular ecology of reptilian sex determination
      and permitted hypothesis building to help guide future functional studies on the
      epigenetic transduction of external cues in TSD versus GSD systems.

PMID- 30278450
TI  - MARCH9 Suppresses Lung Adenocarcinoma Progression by Downregulating ICAM-1.
AB  - BACKGROUND/AIMS: To investigate the clinical significance and functional
      mechanisms of membrane-associated RING-CH protein 9 (MARCH9) in lung
      adenocarcinoma (LAC). METHODS: Immunohistochemistry staining was performed to
      explore the expression of MARCH9 in LAC tissues and adjacent normal lung tissues.
      Patients' prognosis was evaluated using overall survival. The prognostic role of
      MARCH9 was tested with univariate and multivariate analyses. To confirm the
      effect of MARCH9 in cell proliferation and invasion, overexpression of MARCH9 was
      induced in two LAC cell lines. Cell cycle, apoptosis, migration, invasion, and
      immunoprecipitation experiments were performed to further explore the signaling
      pathways involved. RESULTS: Analysis of a series of 143 clinical samples revealed
      that MARCH9 was down-regulated in tumor tissues compared with normal lung
      tissues, and this was closely associated with lymph node metastasis (P = 0.004).
      Univariate and multivariate analyses indicated that MARCH9 was an independent
      prognostic biomarker for LAC; low MARCH9 expression indicated poor overall
      survival. Cellular studies with A549 and H1299 cells demonstrated that MARCH9 can
      attenuate tumor migration and invasion but had little effect on cell cycle or
      apoptosis. Moreover, an interaction between MARCH9 and ICAM-1 protein was
      identified, and overexpression of MARCH9 was found to attenuate the oncogenic
      effect of ICAM-1, suggesting that MARCH9 may inhibit tumor progression by
      downregulating ICAM-1 signaling. CONCLUSION: MARCH9 downregulation in LAC tissues
      correlated with poor clinical outcomes. MARCH9 may serve as a novel biomarker and
      potential therapeutic target for LAC.

PMID- 30278452
TI  - Long Non-Coding MALAT1 Functions as a Competing Endogenous RNA to Regulate
      Vimentin Expression by Sponging miR-30a-5p in Hepatocellular Carcinoma.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) has a high morbidity as well as
      mortality and is believed to be one of the most prevalent cancers worldwide. The
      long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1
      (MALAT1) is involved in numerous cancers, including HCC. This study aimed to
      explore the role of MALAT1 in HCC progression. METHODS: The expression levels of
      MALAT1 and Vimentin in HCC tissues and relative pair-matched adjacent normal
      liver tissues were analyzed by RT-PCR, and immunohistochemistry. Using
      bioinformatics analysis and dual-luciferase assay, we examined the correlation
      between MALAT1 and miR-30a-5p. Dual-luciferase assay and western blotting
      suggested that Vimentin was a target of miR-30a-5p. A wound healing assay and
      transwell assays were employed to determine the effect of MALAT1 and miR-30a-5p
      on cell migration and invasion in HCC. RESULTS: Our data demonstrated that the
      levels of MALAT1 and Vimentin were upregulated in HCC tissues and that miR-30a-5p
      was a direct target of MALAT1. Silenced MALAT1 and overexpressed miR-30a-5p each
      inhibited cell migration and invasion. Additionally, dual-luciferase assay and
      western blotting demonstrated that MALAT1 could competitively sponge miR-30a-5p
      and thereby regulate Vimentin. CONCLUSION: Our data suggest that MALAT1 acts as
      an oncogenic lncRNA that promotes HCC migration and invasion. Therefore, the
      MALAT1-miR-30a-5p-Vimentin axis is a potential therapeutic target and molecular
      biomarker in HCC.

PMID- 30278454
TI  - Stay Gathered Rather than Scattered: Strategies of Common Marmosets during
      Agonistic Interactions with Birds in the Atlantic Rain Forest.
AB  - To reduce the vulnerability of their small body size, common marmosets live in
      large and cohesive social groups. Thus, we hypothesized that in order to
      compensate for small body size and predation risk, individuals of common
      marmosets will stay gathered rather than scattered when foraging for eggs and/or
      nestling birds. Furthermore, in order to avoid costly injuries and eventual
      predation risks, for both sides, the majority of interactions among common
      marmosets and small birds will not involve direct physical contact. The study was
      developed in a small fragment of Atlantic Forest in the northeast of Brazil. We
      recorded a total of 115 interactions between common marmosets (Callithrix
      jacchus) with 7 different bird species. As expected, agonistic interactions were
      significantly more frequent when the marmosets were gathered. Also, most
      agonistic interactions by the birds toward common marmosets involved overflights
      without physical contact. Apparently, the set of avoidance behavior leads to a
      reduced predation risk for both sides. It appears that dispersed marmosets do not
      represent an imminent threat that justifies an agonistic reaction by the birds as
      the latter appear to avoid exposing themselves to unnecessary danger during
      agonistic interactions, especially when the marmosets are gathered.

PMID- 30278453
TI  - Hepatitis E Virus Genotype 3 Genomes from RNA-Positive but Serologically Negative
      Plasma Donors Have CUG as the Start Codon for ORF3.
AB  - Hepatitis E virus (HEV) is a pathogen that causes hepatitis worldwide. Molecular
      studies have identified HEV RNA in blood products although its significance is
      not understood. This study was undertaken to characterize HEV genomes in
      asymptomatic plasma donors from Sweden and Germany lacking anti-HEV. Complete
      open reading frames (ORFs) were obtained from HEV strains in 5 out of 18 plasma
      donors who tested positive for HEV RNA. All strains had CUG as the start codon of
      ORF3, while 147 GenBank strains all had AUG as the start codon (p < 0.0001). This
      substitution was found in both interrelated and unrelated strains belonging to
      different phylogenetic clades. The HEV strains from the seronegative plasma
      donors had no other substitution in common, which may be why the CUG substitution
      seems to explain the seronegativity.

PMID- 30278455
TI  - Hepatitis E Virus Genotype 1 and Hepatitis A Virus Dual Infection in Pediatric
      Patients with a Low Socioeconomic Status from Mexico.
AB  - OBJECTIVE: We aimed to detect and characterize hepatitis E virus (HEV) RNA in
      sera samples from a pediatric population infected with the hepatitis A virus
      (HAV) exhibiting acute hepatitis and to correlate the infection status with the
      clinical outcome. METHODS: Seventy-five ELISA-positive samples from children
      containing anti-HAV and anti-HEV IgM were used to amplify and characterize
      partial regions within HEV ORF2. A statistical comparison of clinical data
      between HEV IgM-positive/HEV RNA-positive patients and HEV IgM-positive/HEV RNA
      negative patients was performed. RESULTS: Thirteen out of 75 IgM-positive samples
      provided amplification of discrete regions of the HEV genome. Nested RT-PCR-based
      detection and subsequent sequencing of 5 samples confirmed the identity of HEV
      genotype 1 (G1), which had not been previously reported in Mexico. Though not
      significant, a trend towards exacerbated clinical manifestations was found in HEV
      RNA-positive patients relative to HEV RNA-negative patients. CONCLUSIONS: An
      elevated rate of G1 RNA was detected. Hepatitis E seems to be a neglected disease
      in Mexico and epidemic strains of HEV are likely to play a role as causative
      agents of acute hepatitis in highly exposed children. Although HAV is endemic in
      Mexico, an HEV-RNA detection rate of 17% in co-infected samples shows the need
      for screening for HEV as a part of future vaccination strategies.

PMID- 30278456
TI  - Schema Modes and Personality Disorder Symptoms in Alcohol-Dependent and Cocaine
      Dependent Patients.
AB  - Substance use disorders (SUD) and personality disorders co-occur frequently. This
      relationship might be understood by studying schema modes (a key concept in
      Schema therapy), which explain the dysfunctions characterizing personality
      disorder patients. In the present study, we compared the schema modes and
      personality disorder symptoms between alcohol-dependent patients, cocaine
      dependent patients and healthy controls. We found indications that specific
      schema modes are specific for SUD patients. However, no differences between
      specific subtypes of SUD patients (alcohol- vs. cocaine-dependent patients) could
      be found regarding schema modes. Further, it is suggested that borderline
      personality disorder symptoms are highly relevant for SUD patients. A first step
      is made in understanding the relationship between schema modes and SUD, which may
      contribute to the understanding of the problematic behaviour seen in patients
      with personality disorders and SUD (and may possibly contribute to the
      improvement of the treatment of this group of patients).

PMID- 30278457
TI  - Effect of Fluoride Toothpaste Containing Nano-Sized Sodium Hexametaphosphate on
      Enamel Remineralization: An in situ Study.
AB  - OBJECTIVE: To evaluate the remineralizing potential of a conventional toothpaste
      (1,100 ppm F) supplemented with nano-sized sodium hexametaphosphate (HMPnano) in
      artificial caries lesions in situ. DESIGN: This double-blinded crossed study was
      performed in 4 phases of 3 days each. Twelve subjects used palatal appliances
      containing 4 bovine enamel blocks with artificial caries lesions. Volunteers were
      randomly assigned into the following treatment groups: no F/HMP/HMPnano
      (Placebo); 1,100 ppm F (1100F); 1100F plus 0.5% micrometric HMP (1100F/HMP) and
      1100F plus 0.5% nano-sized HMP (1100F/HMPnano). Volunteers were instructed to
      brush their natural teeth with the palatal appliances in the mouth for 1 min (3
      times/day), so that blocks were treated with natural slurries of toothpastes.
      After each phase, surface hardness post-remineralization (SH2), integrated
      recovery of subsurface hardness (DeltaIHR), integrated mineral recovery
      (DeltaIMR) and enamel F concentration were determined. Data were submitted to
      analysis of variance and Student-Newman-Keuls' test (p < 0.001). RESULTS: Enamel
      surface became 42% harder when treated with 1100F/HMPnano in comparison with
      1100F (p < 0.001). Treatment with 1100F/HMP and 1100F/HMPnano promoted an
      increase of ~23 and ~87%, respectively, in DeltaIHR when compared to 1100F (p <
      0.001). In addition, DeltaIMR for the 1100F/HMPnano was ~75 and ~33% higher when
      compared to 1100F and 1100F/HMP respectively (p < 0.001). Enamel F uptake was
      similar among all groups except for the placebo (p < 0.001). CONCLUSION: The
      addition of 0.5% HMPnano to a conventional fluoride toothpaste was able to
      promote an additional remineralizing effect of artificial caries lesions.

PMID- 30278459
TI  - Comparison of Bubble CPAP Devices Using RAM Cannula for Extubation Failure in
      Very Low Birth Weight Infants: Randomized and Cohort Studies.
AB  - INTRODUCTION: Bubble continuous positive airway pressure (bCPAP) generates a
      variable pressure due to bubble size and frequency, and these pressure
      oscillations may contribute to lung recruitment and gas exchange. Single-outlet
      bCPAP devices generate larger pressure fluctuation than bCPAP devices with
      diffusers, but clinical efficacy is unclear. Our hypothesis was that a single
      outlet bCPAP device (B&B Bubbler(c)) would decrease extubation failure and
      improve oxygenation compared with a bCPAP device with a diffuser (BabiPlus(c)).
      METHODS: Bench testing of bCPAP devices with the RAM(c) cannula determined
      pressure averages, fluctuations, and CPAP transmission at prongs. The B&B
      Bubbler(c) and the BabiPlus(c) devices were compared for oxygenation and bCPAP
      failure within 72 h of extubation in a randomized trial in infants less than
      1,250 g (n = 43). Additionally, a cohort study with infants extubated to
      BabiPlus(c) (n = 128), B&B Bubbler(c) (n = 119), and noninvasive positive
      pressure ventilation (NIPPV) (n = 107) were compared. RESULTS: Small differences
      in pressure fluctuations between bCPAP devices are attenuated by the RAM(c)
      cannula. Pressures at RAM(c) prongs are 62% of set pressure. The bCPAP extubation
      failure rate (35%) and oxygenation were similar between the bCPAP devices. bCPAP
      success was associated with lower FiO2 at extubation and decreased need for
      additional FiO2 in both groups. In the setting of the RAM(c) cannula, there were
      no differences in extubation failure rate for infants extubated to bCPAP or
      NIPPV. CONCLUSIONS: There were no clinical differences at extubation between the
      B&B Bubbler(c) and BabiPlus(c) devices. Oxygenation may predict bCPAP failure.
      The use of the RAM(c) cannula as a bCPAP interface should be more closely
      examined.

PMID- 30278458
TI  - Total Saponins of Aralia Elata (Miq) Seem Alleviate Calcium Homeostasis Imbalance
      and Endoplasmic Reticulum Stress-Related Apoptosis Induced by Myocardial
      Ischemia/Reperfusion Injury.
AB  - BACKGROUND/AIMS: Total saponins of Aralia elata (Miq) Seem (AS) from the Chinese
      traditional herb Long ya Aralia chinensis L. reportedly provide cardioprotective
      effects, but the exact mechanisms require further study. Previous studies have
      showed that myocardial ischemia/ reperfusion injury (MIRI) was related to calcium
      homeostasis imbalance and endoplasmic reticulum stress (ERS). Thus, this study
      aimed to demonstrate protective effects of AS on MIRI. METHODS: After
      administrating AS for 5 days, the left anterior descending artery coronary artery
      of Sprague-Dawley (SD) rats was ligated for 30 min. After 48 h of reperfusion,
      haemodynamics, Evans blue/ 2,3,5-triphenyltetrazolium chloride (TTC) staining,
      hematoxylin-eosin (HE) staining, masson staining and the levels of lactate
      dehydrogenase (LDH) and creatine kinase (CK), superoxide dismutase (SOD),
      malondialdehyde (MDA) were detected to assess MIRI. ATPase activity and Western
      Blot were used to study the mechanisms. RESULTS: Compared with IR group, AS
      treatment groups could significantly reduce myocardial infarct size; improve
      myocardial pathologic progress; decrease content of LDH, CK, and MDA; increase
      content of SOD; and restore the activities of Ca2+-Mg2+-ATPase, Na+-K+-ATPase,
      sarcoplasmic reticulum Ca2+-ATPases (SERCA), and calcineurin (CaN). AS treatment
      groups also significantly up-regulated the expression of GRP78, C/EBP homologous
      protein (CHOP), and Bax, and down-regulated the expression of Bcl-2, all similar
      to the effects of ERS. CONCLUSION: These findings illustrated that AS could
      prevent myocardial ischemia/reperfusion injury and reduce calcium homeostasis
      imbalance and ERS-related apoptosis.

PMID- 30278460
TI  - A New Transcutaneous Method for Breast Cancer Detection with Dogs.
AB  - We developed a new transcutaneous method for breast cancer detection with dogs: 2
      dogs were trained to sniff skin secretion samples on compresses that had been
      worn overnight by women on their breast, and to recognize a breast cancer sample
      among 4 samples. During the test, the dogs recognized 90.3% of skin secretion
      breast cancer samples. This proof-of-concept study opens new avenues for the
      development of a reliable cancer diagnostic tool integrating olfactory abilities
      of dogs.

PMID- 30278462
TI  - Effect of Delayed Cord Clamping of Term Babies on Neurodevelopment at 12 Months:
      A Randomized Controlled Trial.
AB  - BACKGROUND: Delayed cord clamping (DCC) is associated with an improved iron
      status at 8 months, a reduction of anemia at 12 months, and an improved
      development at 4 years. Assessment of the development after DCC has not been
      performed earlier in a setting with a high prevalence of iron deficiency.
      OBJECTIVE: The aim of this paper was to investigate the effects of DCC compared
      to early cord clamping (ECC) on the development evaluated with the Ages and
      Stages Questionnaire (ASQ) at 12 months of age. METHOD: We conducted a randomized
      controlled trial investigating the effect of DCC (>=180 s) versus ECC (<=60 s) in
      540 full-term deliveries. Twelve months after delivery, the parents reported
      their infant's development by ASQ. Infants having a score < 1 standard deviation
      (SD) under the mean score were considered "at risk" of affected neurodevelopment.
      RESULTS: At 12 months of age, 332 (61.5%) infants were assessed. Fewer children
      in the DCC group were "at risk" of having affected neurodevelopment measured by
      the ASQ total score, 21 (7.8%) versus 49 (18.1%) in the ECC group. The relative
      risk was 0.43 (0.26-0.71). Infants in the DCC group had higher mean total scores
      (SD), 290.4 (10.4) versus 287.2 (10.1), p = 0.01. Significantly fewer infants in
      the delayed group were "at risk" and had higher scores in the domains
      "communication", "gross motor", and "personal-social". CONCLUSIONS: DCC after 3
      min was associated with an improvement of the overall neurodevelopment assessed
      at 12 months of age as compared to infants in the group with cord clamping within
      1 min.

PMID- 30278461
TI  - Mining Prognostic Significance of MEG3 in Human Breast Cancer Using
      Bioinformatics Analysis.
AB  - BACKGROUND/AIMS: Maternally expressed gene 3 (MEG3) is an imprinted gene with
      maternal expression, which may function as a tumor suppressor by inhibiting
      angiogenesis. To identify the prognostic value of MEG3 in breast cancer,
      systematic analysis was performed in this study. METHODS: To evaluate gene
      alteration during breast carcinogenesis, we explored MEG3 expression using the
      Serial Analysis of Gene Expression Genie suite and Oncomine analysis. The
      prognostic roles of MEG3 in breast cancer were investigated using the PrognoScan
      database. The heat map and methylation status of MEG3 were determined using the
      UCSC Genome Browser. RESULTS: We found that MEG3 was more frequently
      downregulated in breast cancer than in normal tissues and this correlated with
      prognosis. However, estrogen receptor and progesterone receptor status were found
      to be positively correlated with MEG3 expression. Conversely, basal-like status,
      triple-negative breast cancer status, and Scarff Bloom & Richardson grade
      criterion were negatively correlated with MEG3 expression. Following data mining
      in multiple big data databases, we confirmed a positive correlation between MEG3
      and heparan sulfate proteoglycan 2 (HSPG2) expression in breast cancer tissues.
      CONCLUSION: MEG3 could be adopted as a marker to predict the prognosis of breast
      cancer with HSPG2. However, large-scale and comprehensive research is needed to
      clarify our results.

PMID- 30278463
TI  - Anaesthesia and Perioperative Care for Transoral Robotic Surgery.
AB  - Minimally invasive surgical techniques have gained increasing interest in recent
      years for their conferred recovery and postoperative advantages. Robot-assisted
      surgery requires special consideration for anaesthetic and perioperative
      management. The introduction of robot- assisted intra-oral surgery has important
      implications on anaesthesia provision, airway management and patient safety. Due
      to its relatively novel use we explore these considerations alongside our own
      experience in this field.

PMID- 30278464
TI  - The Effect of LncRNA H19/miR-194-5p Axis on the Epithelial-Mesenchymal Transition
      of Colorectal Adenocarcinoma.
AB  - BACKGROUND/AIMS: Since the combined actions of lncRNAs and miRNAs have been
      considered to be involved in the occurrence and development of various neoplasms,
      the main purpose of this study was to discover whether and how lncRNA H19 and miR
      194 influenced the epithelial-mesenchymal transition (EMT) process of colorectal
      adenocarcinoma (CRA). METHODS: Totally 214 pairs of CRA and adjacent normal
      tissues were collected, and 5 human CRA cell lines (i.e. HCT116, HT-29, RKO SW280
      and Lovo) were purchased. Quantitative reverse transcription-polymerase chain
      reaction (qRT-PCR) was adopted to quantify the H19 and miR-194-5p expressions in
      cells and tissues. The expressions of FoxM1, E-cadherin, vimentin, N-cadherin
      were determined using western blot. On the side, si-H19, si-NC, miR-194-5p mimic,
      miR-194-5p inhibitor and negative control (NC) were transfected into CRA cell
      lines. Meanwhile, the invasive, migratory and proliferative conditions of the
      cells were assessed through transwell, wound healing and colony-forming
      experiments, with final verification of the relationship between H19 and miR-194
      5p employing dual-luciferase reporter gene assay. RESULTS: Highly-expressed H19,
      lowly-expressed miR-194-5p, low-grade differentiation and lymph node metastasis
      appeared as the independent predictors of unfavorable prognosis in CRA patients'
      (all P< 0.05). It indicated that FoxM1 expression displayed positive correlations
      with H19 expression, yet negative associations with miR-194-5p expression within
      CRA tissues (P< 0.05). In addition, transfection of H19-siRNA and miR-145-5p
      mimic triggered a conspicuous increase in E-cadherin expression, as well as an
      evidently down-regulation in vimentin and N-cadherin expressions within HT29 and
      RKO cells (P< 0.05). On the other hand, the invasive and migratory capacities of
      CRA cells were significantly hindered (P< 0.05). Moreover, the luciferase
      reporter gene assay confirmed that H19 modified miR-194-5p expression through
      directly targeting at it (P< 0.05). Ultimately, FoxM1 could reverse the role of
      miR-194-5p in inhibiting invasion, migration and EMT of CRA cells (P< 0.05).
      CONCLUSION: LncRNA H19/miR-194/FoxM1 axis could serve as a profound target for
      the diagnosis and treatment of CRA.

PMID- 30278465
TI  - The Novel Effect of Immunomodulator-Glatiramer Acetate on Epileptogenesis and
      Epileptic Seizures.
AB  - BACKGROUND/AIMS: Immunological mechanisms can be triggered as a response to
      central nervous system insults and can lead to seizures. In this study an
      investigation was made to determine if glatiramer acetate (GA), an
      immunomodulator currently used in the treatment of multiple sclerosis, could
      protect rats from pilocarpine-induced seizures and chronic epilepsy. METHODS: Two
      groups of adult male Sprague-Dawley rats, experimental (GA) and control, were
      used in the study. The systemic IL-1alpha and IL-1beta levels at baseline were
      checked as well as status epilepticus (SE), and the spontaneous recurrent seizure
      (SRS) stage by enzyme-linked immunosorbent assay. The GA group was given GA (150
      MUg/kg, ip) and the control group was given a saline injection prior to
      pilocarpine-induced seizures. Seizure susceptibility, severity and mortality were
      evaluated, using Racine seizure classification and hippocampal damage was
      evaluated by Nissl staining. The GA group received GA (150 MUg/kg/day, ip) daily
      after SE, and the chronic spontaneous seizures were evaluated by long-term video
      recording, and mossy fiber sprouting was evaluated by Timm staining. The IL
      1alpha and IL-1beta levels were correlated with seizure activities. The TNF-alpha
      level in the hippocampus was determined at the SRS stage by immunohistochemistry.
      The effect of GA on ionic currents and action potentials (APs) in NG108-15
      differentiated neurons was investigated using patch-clamp technology. RESULTS: It
      was found that latency to severe seizures was significantly longer in the GA (p <
      0.01) group, which also had SE of shorter duration and less frequent SRS (p <
      0.01). GA attenuated acute hippocampal neuron loss and chronic mossy fiber
      sprouting in the CA3 and the SRS-reduction correlated with the reduction of IL
      1alpha, but not with IL-1beta or TNF-alpha levels. Mechanistically, GA reduced
      the peak amplitude of voltage-gated Na+ current (INa), with a negative shift in
      the inactivation curve of INa and reduced the amplitude of APs along with
      decreased firing of APs. CONCLUSION: GA might serve as a neuroexcitability
      modulator which attenuates pilocarpine-induced acute and chronic excitotoxicity.
      Sodium channel attenuation was partially independent of the immunomodulatory
      effect.

PMID- 30278466
TI  - Prognostic Role of High Stathmin 1 Expression in Patients with Solid Tumors:
      Evidence from a Meta-Analysis.
AB  - BACKGROUND/AIMS: Several recent studies have demonstrated that Stathmin
      1expression may be closely associated with prognosis in patients with various
      types of cancers. In the present study, we conducted a meta-analysis of all
      available studies in the English literature to assess the prognostic value of
      Stathmin 1expression in patients with solid cancers. METHODS: The online
      databases PubMed, Embase, and Web of Science were searched for literature
      regarding Stathmin 1 and its association with patient outcomes associated with
      solid cancers. RESULTS: A total of 23 articles including 26 studies that
      contained 5 335 patients were retrieved and analyzed. Our results indicated that
      high Stathmin 1 expression yielded a worse overall survival (OS) (hazard ratio
      [HR] = 2.17, 95% confidence interval [CI]: 1.81-2.60), disease-free survival
      (DFS) (HR = 2.46, 95% CI: 2.00-3.02), disease-specific survival (DSS) (HR = 1.98,
      95% CI: 1.58- 2.47) and progression-free survival (PFS)/recurrence-free survival
      (RFS) (HR = 2.09, 95% CI: 1.51-2.89). Furthermore, the association of high
      Stathmin 1 expression with poor survival was significant even for sub-group
      analyses of different tumor types, ethnicities, methods used to calculate HRs,
      detected methods, and analysis types. CONCLUSION: In summary, this meta-analysis
      determined that high Stathmin 1 expression is associated with poor prognosis in
      patients with solid cancers and expression of this protein could be a clinically
      useful prognostic biomarker.

PMID- 30278467
TI  - Resistance to Fas-Mediated Apoptosis Does Not Correlate to Structural Alterations
      or Expression Changes of the Death Receptor in Papillary Thyroid Carcinomas.
AB  - BACKGROUND: Malignant cells exhibit significant resistance to FAS-mediated cell
      death, through different processes, including FAS mutations, soluble FAS
      expression, or FAS transcriptional dysregulation by P53, eventually escaping from
      immune surveillance. Since thyroid carcinomas were shown to be resistant to FAS
      mediated apoptosis, we investigated the above mechanisms in thyroid carcinoma
      samples. METHODS: Thirty-seven thyroid carcinoma samples were analyzed for
      mutations in FAS exon 9 and TP53 exons 5-8 and protein expression by means of
      immunohistochemistry. Moreover, thyroid carcinoma mRNA samples were subjected to
      reverse transcription - PCR, to evaluate the relative expression of transmembrane
      FAS versus its soluble form. RESULTS: Analysis revealed indications for TP53
      mutations in the anaplastic carcinomas, but not in the other thyroid specimens
      examined for TP53 or FAS exon 9 mutations. FAS receptor expression was observed
      in almost all thyroid specimens (97%) with significant up-regulation in papillary
      carcinomas. P53 nuclear staining was observed only in anaplastic carcinomas. Full
      length FAS mRNA was detected in all specimens examined, with soluble FAS mRNA
      being either absent or present in very low amounts. CONCLUSIONS: Our results
      denote that FAS death domain or TP53 DNA-binding domain mutations, down
      regulation of FAS receptor expression, or expression of FAS soluble isoform are
      not responsible for the seeming inhibition of FAS-mediated apoptosis in papillary
      thyroid carcinoma cells.

PMID- 30278468
TI  - [Externally Acquired Radiological Image Data and Reporting for the Clinical
      Routine, Conference and Boards - Legal Aspects of the Second Opinion in Germany].
AB  - BACKGROUND: Because of an increasing number of boards and conferences, the number
      of second opinion readings of externally acquired image data is growing
      dramatically. In this review article we intend to give medical and legal
      recommendations for the documentation and interpretation of externally acquired
      radiological data for second opinions and board presentations based on German
      jurisdiction. METHOD: Using the FAQ format as a dialog between radiologists and
      medical legal experts, we answer the most crucial questions regarding correct
      documentation and interpretation for externally acquired radiological image data
      based on an up-to-date literature search. RESULTS: Based on the unity of
      radiological image data and the corresponding written report according to the
      radiation protection law, the primary report should be present when composing a
      second opinion. If the primary external report is not present, this should be
      mentioned as a limitation. All radiological second opinions should be documented
      in written form. This is especially important in cases of discrepant findings.
      Legally, the attending physician is responsible for selecting the radiological
      opinion. The radiologist should not rely on the written primary report without
      personal reevaluation. Legally, it would be considered radiological malpractice
      if the external image data and previous image data are not evaluated personally.
      CONCLUSION: From a legal point of view, there are explicit recommendations
      regarding thorough documentation of a second opinion as an independent medical
      service in all cases.

PMID- 30278470
TI  - Catheter-Based Computed Tomography Angiography in Anterolateral Thigh Perforator
      Mapping of Chinese Patients.
AB  - BACKGROUND:  During reconstructive surgery, anterolateral thigh (ALT) flap
      harvest is challenging due to variation and uncertainty in perforator
      distribution. We performed a pilot study to identify the predictive value of
      catheter-based computed tomography angiography (C-CTA) and traditional CTA (T
      CTA) in ALT perforator mapping for patients whose ALT perforators were difficult
      to identify. METHODS:  Thirty-four consecutive T-CTA/C-CTA-mapped ALT flaps were
      evaluated for extremity reconstruction. The perforator location, origin, and
      course were compared between T-CTA/C-CTA imaging and intraoperative findings. The
      mapping efficiency of T-CTA and C-CTA was compared thoroughly. RESULTS:  Among
      the 34 ALT thigh flaps, 117 (36) of the 130 perforators identified
      intraoperatively were visible on C-CTA (T-CTA) in a subgroup of Chinese limb
      trauma patients with limited activity. C-CTA showed a satisfactory efficiency in
      perforator mapping, which was much better than the efficiency of T-CTA. C-CTA
      also showed a much better sensitivity (90.00 vs. 27.69%), specificity (94.74 vs.
      66.67%), and accuracy (91.07 vs. 36.69%), and a much lower false-positive (1.68
      vs. 26.53%), and false-negative rate (10.00 vs. 72.31%). Moreover, C-CTA could
      accurately predict the origin and septocutaneous or intramuscular course in all
      identified perforators. All flaps were elevated successfully and survived.
      CONCLUSIONS:  C-CTA outperforms T-CTA in the preoperative perforator mapping of
      ALT flaps in a subgroup of Chinese limb trauma patients. C-CTA should be the
      method of choice for perforator mapping in patients whose ALT flaps are intended
      for extremity reconstruction.

PMID- 30278471
TI  - Inpatient Rehabilitation for Children and Adolescents With Diabetes in Germany
      Between 2006 and 2013.
AB  - INTRODUCTION: In Germany, inpatient rehabilitation is a well-established additive
      option in the therapeutic concept for children and adolescents with diabetes.
      However, its contribution in pediatric diabetes care is not known exactly. Our
      objective was to analyze inpatient rehabilitation in pediatric diabetes over
      eight years in Germany. METHODS: We requested secondary data from the German
      Statutory Pension Insurance Scheme to evaluate all completed inpatient
      rehabilitations for children and adolescents with diabetes (ICD-code E10-14)
      reimbursed by this institution between 2006 and 2013. For each type of diabetes,
      we analyzed the distribution of admissions by year, age-group, sex, nationality,
      and other documented diagnoses. All analyses were conducted via remote computing
      with IBM SPSS Version 24. RESULTS: Between 2006 and 2013, 5,403 admissions to
      inpatient rehabilitation for 4,746 children and adolescents with diabetes were
      documented. For type 1 diabetes (T1D; 88.5% of admissions), the number of yearly
      admissions increased from 458 in 2006 to 688 in 2013 (p=0.013), especially for
      age-group>5-10. The increase for type 2 diabetes (T2D) was not significant.
      Admissions were more frequent for girls (53.6%, p<=0.001), age>10-15 years
      (42.8%, p=0.001), and German nationality (98.5%). Obesity (T1D: 11.1%; T2D:
      87.9%) and mental disorders (T1D: 11.6%; T2D: 27.4%) were the most frequent
      documented diagnoses in addition to diabetes. CONCLUSION: This study provides a
      comprehensive overview of inpatient rehabilitation for children and adolescents
      with diabetes over many years in Germany. Until 2013, inpatient rehabilitation
      remained important in pediatric diabetes care, especially for children with
      mental disorders or obesity.

PMID- 30278469
TI  - [Regulation of bone metabolism by the Wnt signaling pathway].
AB  - The development and homeostasis of multicellular organisms depends on a complex
      cellular interaction between proliferation, migration, differentiation, adhesion,
      and cell death. Wnt signaling pathways coordinate these different cellular
      responses. Wnt signaling plays a role as a regulatory pathway in the osteogenic
      differentiation of mesenchymal stem cells. The Wnt signaling pathway is an
      attractive therapeutic target with the potential to directly modulate stem cells
      responsible for the regeneration of skeletal tissue. Recent studies indicate that
      Wnt ligands are capable of promoting bone growth, suggesting that Wnt factors
      could be used to stimulate bone healing in osteogenic disorders.

PMID- 30278472
TI  - alpha-Glucosidase Inhibitory and Anti-Inflammatory Coumestans from the Roots of
      Dolichos trilobus.
AB  - Four new coumestans dolichosins A - D (1: -4: ) were isolated from the roots of
      Dolichos trilobus, together with four known compounds: isosojagol (5: ), phaseol
      (6: ), psoralidin (7: ), and 4",5"-dehydroisopsoralidin (8: ). Their structures
      were elucidated on the basis of spectroscopic data interpretation, mass
      spectrometric analyses, and the comparison with literature data of related
      compounds. The anti-inflammatory activity of these compounds (1: -8: ) was
      evaluated through the inhibition of nitric oxide production in lipopolysaccharide
      activated murine macrophage RAW 264.7 cells, in which compounds 1: and 6:
      displayed moderate inhibitory activity and no cytotoxic effects. In a alpha
      glucosidase inhibitory assay, compounds 1: and 5: -8: exhibited appreciable
      inhibition on alpha-glucosidase. Especially compounds 1, 7: , and 8: showed IC50
      values lower than 20.0 uM.

PMID- 30278473
TI  - New trends and methods for carbon isotope chemistry.

PMID- 30278474
TI  - PUBLICATION OF THE SECOND EDITION OF THE FIRMS GOOD PRACTICE GUIDE FOR ISOTOPE
      RATIO MASS SPECTROMETRY.

PMID- 30278476
TI  - [Prologue].

PMID- 30278477
TI  - [Introduction].

PMID- 30278475
TI  - Outcomes of mitral valve surgery during concomitant aortic valve replacement.
AB  - BACKGROUND: This study evaluates outcomes of mitral valve surgery (MVS),
      replacement (MVR), and repair (MVr), during concomitant aortic valve replacement
      (AVR). METHODS: Patients undergoing MVS with concomitant AVR between 2011 and
      2017 at a single center were reviewed. Patients were stratified into MVR versus
      MVr with concomitant AVR. Outcomes included early and midterm mortality, hospital
      re-admissions, re-operations, and complications. Multivariable Cox regression
      analysis was used for risk-adjustment. RESULTS: Four hundred twenty-four patients
      underwent MVS with concomitant AVR: 247 (58.3%) MVr and 177 (41.7%) MVR. In
      unadjusted analysis, there was a non-significant increase in 30-day mortality
      with MVR, with no differences in 1- and 5-year mortality (30-day: 5.6% vs 10.1%,
      P = 0.081; 1-year: 14% vs 18.2%, P = 0.181; 5-year: 35.1% vs 37.8%, P = 0.232).
      Freedom from re-admission and mitral reoperation were comparable. Freedom from at
      least moderate mitral regurgitation at 5 years was 78% in MVr patients. Those
      undergoing MVR had increased postoperative blood transfusions, acute renal
      failure, and pleural effusions requiring drainage (P each <0.05). CONCLUSIONS:
      MVr can be performed during concomitant AVR without an adverse impact on longer
      term outcomes, including mortality, re-admissions, and mitral reoperations. The
      majority of patients have durable repairs at 5 years although durability is less
      than that reported in isolated MVS.

PMID- 30278478
TI  - [Mexican consensus on the diagnosis and treatment of atopic dermatitis in
      adolescents and adults].
AB  - BACKGROUND: The diagnostic approaches and therapeutic strategies of atopic
      dermatitis (AD) are generally inconsistent among physicians and health
      institutions. OBJECTIVE: To develop a consensus statement among experts to reduce
      the variations in practice regarding the diagnosis and treatment of patients >=
      12 years with AD to improve their care. METHODS: Systematic literature search in
      PubMed and GREAT. With methodological support and using the Delphi method, a
      formal consensus was developed among 16 experts in Dermatology and Allergology,
      based on the current evidence and its applicability in the Mexican context. Apart
      from intense electronic communication, several issues of disagreement were
      discussed in two face-to-face meetings. RESULTS: The clinical experts reached
      consensus on 46 statements related to the definition, classification, diagnostic
      strategies and treatment of AD. For the diagnosis we suggest the Williams
      criteria and for severity scoring the SCORAD (by the doctor) and POEM (by the
      patient). In addition to general care and treatment education (workshops), we
      suggest four steps for treatment, depending on severity: 1. Topical treatment
      with anti-inflammatory agents (and systemic: antihistamines/antileukotrienes -low
      level evidence-) 2. Phototherapy, 3. Cyclosporin A and 4. Dupilumab, with the
      possibility of managing this biological earlier on if a fast effect is needed. In
      extrinsic AD we suggest evaluating the addition of allergen immunotherapy or an
      elimination diet, if there is an IgE-mediated respiratory or food allergy,
      respectively. CONCLUSION: The panel of experts reached consensus on relevant
      aspects of AD with a focus on the transcultural adaptation of recent evidence.

PMID- 30278479
TI  - Assessment of treatment outcomes in patients with advanced hilar
      cholangiocarcinoma (stages III-IV): Clinical significance of interventional
      therapy.
AB  - The clinical significance of palliative interventional therapy in the management
      of patients with advanced hilar cholangiocarcinoma (HCCA; stages III-IV) has yet
      to be studied. The present work was aimed to compare the clinical outcomes of the
      patients treated with surgery or interventional therapy.A total of 90 patients
      with advanced HCCA, who admitted Fuyang First People's Hospital from May 2015 to
      February 2016, were enrolled. Forty-five of them were assigned to the
      experimental group receiving biliary drainage as the interventional therapy, and
      the remaining 45 patients were designated as the conventional group receiving
      radical/palliative surgery. Before and after the treatment total bilirubin from
      blood was measured. The length of treatment and medical cost were also examined.
      All patients were followed up for at least 1 year after the treatment.For both
      the experimental and conventional groups, the serum bilirubin levels after
      treatment were significantly lower than those before treatment (P < .05);
      however, no significant differences between groups were seen. There were no
      significant differences between experimental and conventional groups in the
      incidence of postoperative complications and survival outcomes. Of note, the
      length of treatment of the experimental group was substantially shorter than that
      of the conventional group (P < .05). The medical expense of the experimental
      group was only about one-third of that of the conventional group (P <
      .05).Although the interventional therapy does not improve patients' survivals and
      reduce the incidence of complications, it significantly shortens the treatment
      length, reducing substantially the medical expense. This finding provides new
      insights into the treatment strategy for patients with advanced HCCA.

PMID- 30278480
TI  - Biological characteristics of 18F-FDG PET/CT imaging of cerebral alveolar
      echinococcosis.
AB  - This study aims to analyze the characteristics of F-fluorodeoxyglucose positron
      emission tomography/computed tomography (F-FDG PET/CT) for cerebral alveolar
      echinococcosis (CAE).Twenty-five CAE patients underwent F-FDG PET/CT, and the
      diagnosis was confirmed by clinical and surgical pathology. The F-FDG PET/CT
      results were subject to visual and semiquantitative analysis, and the difference
      in F-FDG SUVmax for lesions among the 3 types of CAE was evaluated.In the 25 CAE
      patients, 62 lesions were detected by F-FDG PET/CT, and these lesions were
      classified into 3 types, according to the characteristics of the lesion's uptake
      of F-FDG on PET images: type I, 17 lesions, FDG was concentrated into a mass
      radioactive distribution in the CAE foci; type II, 28 lesions, FDG presented a
      annular concentrated radioactive distribution around the CAE foci; type III, 17
      lesions, FDG in the CAE foci presented a radioactive distribution with defects
      and sparse areas. The difference in F-FDG SUVmax between type I and type II CAE
      was not statistically significant (P > .05), the difference in F-FDG SUVmax
      between type I and type III CAE was statistically significant (P < .001), and the
      difference in F-FDG SUVmax between type II and type III CAE was statistically
      significant (P < .001);The F-FDG PET manifestations of CAE are classified into 3
      types. Both type I and type II may have invasive activity, while the lesions of
      type III CAE show that the focus is relatively stable or at a stationary phase.
      If there are no definite alveolar echinococcus focus in other sites, these
      patients can temporarily delay the treatment. It is recommended that the patient
      should undergo whole body PET/CT once a year to dynamically observe the
      bioactivity and size of type III CAE lesions and assess the presence of new
      echinococcus lesions in the rest of the body.

PMID- 30278481
TI  - Feasibility and Efficacy of Transient Elastography using the XL probe to diagnose
      liver fibrosis and cirrhosis: A meta-analysis.
AB  - BACKGROUND: Transient elastography (TE) has been validated as an effective
      noninvasive tool for the assessment of liver fibrosis. The XL probe is a new
      probe that was initially designed for use in patients with obesity. A meta
      analysis was performed to assess the feasibility and efficacy of TE using the XL
      probe. METHODS: In September 2016, we systematically searched the PubMed and
      Science Direct search engines. The feasibility of TE was evaluated based on the
      failure rate and the results of the unreliable liver stiffness measurement (LSM).
      The efficacy of TE was measured using sensitivity, specificity, and summary
      receiver-operating characteristic as measures/indices assessed in different
      stages of fibrosis. Heterogeneity was measured using the chi-squared test and the
      Q-statistic. We used the 95% confidence interval (95% CI) as an effect measure.
      RESULTS: We included 8 studies in the meta-analysis. When the XL was compared to
      the M probe, the former showed a lower risk of failure rate [relative risk (RR)
      0.24, 95% CI 0.14-0.38]. In patients with a body mass index >=30 kg/m, the XL
      probe showed a statistically significantly lower risk of failure rate (RR 0.16,
      95% CI 0.08-0.32) but no significant improvement (RR 0.76, 95% CI 0.50-1.16) in
      the unreliable LSM result. In patients showing liver fibrosis stage >=F2, the XL
      probe showed a sensitivity of 0.56 (95% CI 0.39-0.72), specificity of 0.71 (95%
      CI 0.61-0.79), and an area under the curve (AUC) of 0.71. The results observed in
      patients with liver fibrosis stage F4 were more promising with a sensitivity of
      0.84 (95% CI 0.76-0.90), specificity of 0.78 (95% CI 0.70-0.84), and an AUC of
      0.88. CONCLUSION: TE using the XL probe demonstrates significant diagnostic
      utility in patients with liver fibrosis and is likely to be more reliable than
      the M probe in patients with obesity. Large prospective multicenter studies are,
      however, necessary to establish the new cut-off values to be used for the XL
      probe in patients with obesity.

PMID- 30278482
TI  - DHCR24 predicts poor clinicopathological features of patients with bladder
      cancer: A STROBE-compliant study.
AB  - To investigate the prognostic value of DHCR24 for patients with bladder cancer
      (BC). We used public bladder cancer microarray studies to evaluate the expression
      of DHCR24 between normal bladder tissues and BC cells, to investigate the
      relationship between the expression of DHCR24 and the clinical features of BC
      patients. Survival analysis was performed to investigate the correlation between
      DHCR24 expression and the survivals of BC patients. Gene set enrichment analysis
      was conducted to identify relevant mechanisms. The results showed that DHCR24 was
      up-regulated in BC cells compared with that in normal bladder tissues (P =
      .0389). Results of chi-square test suggested that BC patients in DHCR24 low
      expression group were proved to have better clinical characteristics (including
      tumor grade, disease progression, T staging, and N staging) as compared with
      those in DHCR24 low expression group (P < .0001, P = .002, P = .005, and P =
      .002, respectively). BC patients in DHCR24 low expression group were associated
      with better cancer-specific survival and overall survival (P < .0001 and P =
      .0008, respectively). DHCR24 might promote the proliferation of BC cells through
      several oncogenesis-associated biological processes (estrogen response, heme
      metabolism, P53 pathway, cholesterol homeostasis, mTORC1 signaling, peroxisome,
      xenobiotic metabolism, glycolysis, and protein secretion). Thus, DHCR24 might be
      a therapeutic target for patients with BC.

PMID- 30278484
TI  - Understanding molecular mechanisms of Rhodiola rosea for the treatment of acute
      mountain sickness through computational approaches (a STROBE-compliant article).
AB  - Rhodiola rosea has been used in the treatment of acute mountain sickness (AMS)
      for a long time, but the mechanism of its action is not still completely clear.
      In this paper, the therapeutic mechanism of R rosea for AMS was investigated by
      analysis of the relationship between R rosea compositions and hypoxia-inducible
      factor 1 (HIF-1) degradation pathway.System biology and network biology,
      computational approaches were used to explore the molecular mechanisms of
      traditional Chinese medicine (TCM).Our results showed that chemical compositions
      of R rosea could inhibit the targets of HIF-1 degradation pathway in multi
      composition/multi-target ways.We conclude that the 18 components with more than 2
      targets and 5 targets (arrest-defective-1 [ARD1], forkhead transcription factor
      [FOXO4], osteosarcoma-9 [OS-9], prolyl hydroxylase 2 [PHD2], human double minute
      2 [Hdm2]) deserve to be noticed, and PHD2, receptor for activated C-kinase1
      (RACK1) and spermidine/spermine-N1-acetyltransferase-1 (SSAT1) may be the targets
      of active ingredients of rhodionin, rhodiosin, and rhodiolatuntoside,
      respectively.

PMID- 30278486
TI  - Primary malignant peripheral nerve sheath tumor of prostate in a young adult: A
      case report.
AB  - RATIONALE: Prostate sarcoma has been reported to represent 0.7% of primary
      prostate malignancies. Leiomyosarcoma and rhabdomyosarcoma are the most common
      sarcomas of the prostate. Malignant peripheral nerve sheath tumor (MPNST) of the
      prostate is very rare. PATIENT CONCERNS: A 22-year-old man presented with gross
      hematuria and voiding difficulty for 2 weeks. Magnetic resonance imaging showed a
      6-cm mass in the left lobe of the prostate. DIAGNOSES: Core needle biopsy results
      revealed high-grade sarcoma, suggestive of poorly differentiated synovial
      sarcoma. The final diagnosis of laparoscopic prostatectomy was MPNST, because it
      did not show the presence of SYT-SSX fusion transcripts on reverse transcription
      polymerase chain reaction analysis. INTERVENTIONS: Adjuvant radiotherapy was
      planned because preoperative positron emission tomography-computed tomography
      (CT) did not show any metastatic lesion and the resection margin was
      microscopically involved. However, chest CT showed multiple lung metastases a
      month after prostatectomy. A chemotherapeutic regimen of doxorubicin and
      ifosfamide was administered. OUTCOMES: The best response to chemotherapy was
      partial response. After several courses of chemotherapy, he died 9 months after
      the surgery. LESSONS: Primary prostate sarcoma and even MPNST are extremely rare.
      MPNST of the prostate has seldom been reported. This report may help diagnose and
      manage the disease.

PMID- 30278483
TI  - Prevalence and determinants of depression in caregivers of cancer patients: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Aim of this study was to estimate the prevalence rate of depression
      in cancer patient caregivers and to identify factors affecting depression and
      quality of life of cancer caregivers. METHODS: Relevant research articles were
      retrieved after literature search in several electronic databases. Random effects
      meta-analyses were performed to obtain pooled estimates of the prevalence rates
      of depression and anxiety; their respective scores, and quality of life scores.
      Significant relationships between depression and factors related to depression
      and quality of life reported in individual studies were identified. RESULTS:
      Thirty studies were included. Overall, 21,149 caregivers were appraised in these
      studies (age 52.65 years [95% CI: 49.65, 55.65]; 31.14% [28.40, 33.89] men). The
      prevalence of depression and anxiety were 42.30% [33.31, 51.29] % and 46.55%
      [35.59, 57.52], respectively. Quality of life score, as measured with Caregiver
      Quality of Life-Cancer scale was 64.55 [47.44, 81.66]. Patient's condition,
      caregiving burden, duration of caregiving, spouse caregiver, caregiver being
      unemployed, caregiver with chronic disease, caregiver's sleep quality,
      caregiver's avoidance, financial problems, and female sex were positively
      associated with depression whereas overall quality of life of caregiver, pre-loss
      grief, caregiver's education level, caregiver's age, caregiver's sense of
      coherence, and caregiver's bondage with patient were negatively associated with
      depression in caregivers. CONCLUSION: A considerably high prevalence of
      depression is found in cancer patient caregivers. Several factors may affect
      depression and their quality of life of cancer patient caregivers.

PMID- 30278485
TI  - Association of CYP2E1 gene polymorphisms with bladder cancer risk: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Human cytochrome P450 (CYP) is an enzyme responsible for the
      metabolic activation of many carcinogens, including nitrosamines. CYP2E1
      represents a major CYP isoform and is expressed in the human urothelial cells.
      Recent studies have investigated the association of CYP2E1 gene polymorphisms
      with bladder cancer risk but have shown contradictory results. Hence, we
      performed a systematic literature review and meta-analysis to assess the
      association between CYP2E1 gene polymorphisms and bladder cancer. METHODS:
      Systematic literature searches were conducted with PubMed, Excerpt Medica
      Database, Science Direct/Elsevier, China National Knowledge Infrastructure, and
      the Cochrane Library up to January 2018 for studies that involved the association
      of CYP2E1 gene polymorphisms with bladder cancer risk. A meta-analysis was
      performed with Review Manager and Stata software. Combined odds ratios (ORs) were
      identified with 95% confidence intervals (CIs) in a random or fixed effects
      model. ETHICS: The protocol was approved by the institutional review board of
      each study center. Written informed consent will be obtained from all patients
      before registration, in accordance with the Declaration of Helsinki. RESULTS:
      Eight studies were identified, including 1733 cases of bladder cancer and 1814
      normal controls. Our results illustrated that there are significant associations
      between CYP2E1 gene polymorphisms and bladder cancer in all genetic models (P <
      .05). The combined ORs and 95% CIs were as follows for each model: additive model
      [OR 0.56; 95% CI (0.38-0.82)]; dominant model [OR 0.79; 95% CI (0.67-0.93)];
      recessive model [OR 0.61; 95% CI (0.41-0.89)]; codominant model [OR 0.80; 95% CI
      (0.67-0.96)]; allele model [OR 0.75; 95% CI (0.59-0.95)]. A subgroup study showed
      that there are also significant associations between CYP2E1 gene polymorphisms
      and bladder cancer in Asian people. However, there are no significant
      associations between CYP2E1 gene polymorphisms and bladder cancer in Caucasian
      populations. CONCLUSIONS: The present study provides evidence for an association
      between CYP2E1 gene polymorphisms and bladder cancer progression, and suggests
      that CYP2E1 gene polymorphisms might be a protective factor against bladder
      cancer in Asian people. However, studies with larger sample sizes are needed to
      confirm the correlation between CYP2E1 gene polymorphisms and bladder cancer.

PMID- 30278487
TI  - Impact of sarcopenia on outcomes of patients undergoing pancreatectomy: A
      retrospective analysis of 107 patients.
AB  - To evaluate the prevalence of sarcopenia in patients undergoing pancreatic
      surgery and to examine its impact on the surgical outcomes and survival of
      patients.Skeletal muscle index (SMI) was measured on preoperative CT. A patient
      was considered sarcopenic if SMI was <38.5 cm/m for a female or <52.4 cm/m for a
      male. Postoperative pancreatic fistula (POPF) and severe morbidity (Clavien>=3)
      were analyzed. Survival of patients with cancer was calculated using the Kaplan
      Meier method.In total, 107 consecutive patients were included. Among them, 50
      (47%) patients were sarcopenic and 65 (60%) were undernourished. The rates of
      severe morbidity and mortality were comparable between sarcopenic and
      nonsarcopenic groups. However, all POPF grade B or C and deaths occurred in the
      sarcopenic or nonsarcopenic overweight group (BMI > 25) with significantly
      lengthened hospital stays (P = .003). After pancreatectomy for cancer, 31 (40.2%)
      patients showed postoperative recurrence and 23 (29.9%) died after a median
      follow-up of 15 +/- 13.5 months. Despite comparable histological types and
      stages, the median overall and disease-free survivals were lower in sarcopenic
      patients (16 months vs not reached, P = .02 and 11.1 months vs 22.5 months; P =
      .04, respectively). The multivariate analysis revealed that, sarcopenia trended
      to increase the risk of death (HR = 2.04, P = .07).Sarcopenia negatively impacted
      short- and long-term outcomes in patients undergoing pancreatectomy.

PMID- 30278488
TI  - Efficacy of common salvage chemotherapy regimens in patients with refractory or
      relapsed acute myeloid leukemia: A retrospective cohort study.
AB  - To assess treatment response and overall survival (OS) in refractory or relapsed
      acute myeloid leukemia (R/R AML) patients treated by different common salvage
      chemotherapy regimens.Medical records data from 142 R/R AML patients were
      reviewed in this retrospective study. Patients were treated with regimens based
      on the following drugs: cytarabine, granulocyte colony-stimulating factor (G
      CSF), and fludarabine (FLAG) (n = 46); cytarabine and G-CSF in addition to
      aclarubicin or daunorubicin (CAG/DAG) (n = 30); cytarabine, G-CSF, and cladribine
      (CLAG) (n = 27); cytarabine, etoposide, and mitoxantrone (MEA) (n = 17);
      cytarabine plus idarubicin, daunorubicin, or mitoxantrone (IA/DA/MA) (n = 12);
      and homoharringtonine, cytarabine, and aclarubicin or daunorubicin (HAA/HAD) (n =
      10).A total of 43 (35.2%) patients achieved complete remission (CR), 60 (49.2%)
      patients achieved overall remission rate (ORR), and 18 (14.8%) patients received
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR. Median
      OS was 8.0 (95% CI 6.6-9.4) months with a 1-year OS rate of (29.9 +/- 3.9)% and 3
      year OS rate of (11.1 +/- 3.6)%. No difference of CR (P = .621), ORR (P = .385),
      and allo-HSCT (P = .537) achievement was observed among different chemotherapy
      regimens. Interestingly, we observed that the CLAG-based regimen did not affect
      CR (P = .165), while it achieved a numerically higher ORR (P = .093) and was an
      independent factor for prolonged OS (P = .016). No other regimens were determined
      to be correlated with CR, ORR, or OS.FLAG-, CAG/DAG-, CLAG-, MEA-, IA/DA/MA- and
      HAA/HAD-based regimens were found to achieve similar CR rates, while the CLAG
      based regimen achieved numerically higher ORR rates and significant favorable OS.
      Therefore, CLAG-based regimens should be a prioritized treatment option for R/R
      AML patients.

PMID- 30278489
TI  - Effects of different doses of intranasal dexmedetomidine on preoperative sedation
      and postoperative agitation in pediatric with total intravenous anesthesia
      undergoing adenoidectomy with or without tonsillectomy.
AB  - Dexmedetomidine is a highly selective alpha2 receptor agonist, this study aimed
      to investigate the effects of different doses of intranasal dexmedetomidine on
      the preoperative sedation and postoperative agitation in pediatric with total
      intravenous anesthesia (TIVA) for adenoidectomy with or without
      tonsillectomy.This is a double-blind placebo-controlled randomized trial.
      Pediatric were randomly divided into the D1, D2, and S groups, each group
      contained 30 patients. Twenty-five to 40 minutes before surgery, the D1 and D2
      groups received intranasally dexmedetomidine 1 MUg kg or 2 MUg kg, respectively,
      while the S group received saline of the same volume. A unified protocol of TIVA
      induction and maintenance was used for the three groups. The preoperative
      sedation, behavior of separation from parents, postoperative agitation, and
      postoperative pain of the children were evaluated.The proportions of satisfactory
      sedation in the D1, D2, and S groups were 63.3%, 76.7%, and 0%, respectively.
      There was a statistically significant difference between D1 and S groups (P =
      .000) and D2 versus S groups (P = .000), while there was no statistically
      significant difference between D1 and D2 groups (P = .399). As for scale on the
      behavior of separation from parents, there was a statistically significant
      difference between D1 and S groups (P = .009) and D2 versus S groups (P = .009),
      whereas there was no significant difference between D1 and D2 groups (P = 1). The
      incidence of postoperative agitation in the D1, D2, and S groups was 43.3%,
      30.0%, and 63.3%, respectively, and there was a statistical difference between D2
      and S groups (P = .010). There was a significant difference in the Pediatric
      Anesthesia Emergence Delirium (PAED) scale between D2 and S groups (P = .029).
      The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) in the D2 group
      was significantly lower than the S group (P = .013).The intranasal
      dexmedetomidine of 1 or 2 MUg kg 25 to 40 minute before induction of anesthesia
      both could deliver effective preoperative sedation, reducing the children's
      distress of separation from parents. Moreover, intranasal dexmedetomidine of 2
      MUg kg could deliver more effective postoperative analgesia and reduce
      postoperative agitation, without prolonging postoperative recovery or causing
      severe adverse events.

PMID- 30278490
TI  - Systematic review and meta-analysis of the effect of probiotic supplementation on
      functional constipation in children.
AB  - BACKGROUND: To evaluate the effect of probiotic supplementation on functional
      constipation in children. METHODS: We performed electronic searches in PubMed,
      Embase, and Cochrane Library without language restriction to identify relevant
      studies from the time of inception of these databases to March 2018. The relative
      risk or weighted mean difference was calculated to evaluate the treatment effect
      of probiotics using random-effects model. RESULTS: We included 4 trials reporting
      data on 382 children with functional constipation. Overall, there were no
      significant differences in treatment success (P = .697), spontaneous bowel
      movements per week (P = .571), fecal soiling episodes per week (P = .642),
      straining at defecation (P = .408), use of lactulose (P = .238), use of laxatives
      (P = .190), fecal incontinence (P = .139), pain during defecation (P = .410),
      flatulence (P = .109), and adverse events (P = .979) between probiotics and
      placebo. Further, the use of probiotics was associated with lower frequency of
      glycerin enema use (weighted mean difference -2.40, P = .004) and abdominal pain
      (weighted mean difference -4.80, P < .001). CONCLUSION: The findings of this
      study suggested that the use of probiotics was associated with significant
      improvement in glycerin enema use and abdominal pain but did not affect the
      treatment success and other function indices.

PMID- 30278491
TI  - Colon cancer and IgG4-related disease with orbital inflammation and bilateral
      optic perineuritis: A case report.
AB  - RATIONALE: Immunoglobulin G4-related disease (IgG4-RD) is an inflammatory
      condition of unknown cause. Cancer might be related to the development of certain
      IgG4-RD but to date, little literature documents it. PATIENT CONCERNS: A 78-year
      old man presented with unilateral proptosis responsive to steroids, initially
      attributed to nonspecific orbital inflammation. DIAGNOSIS: Right hemicolectomy
      was performed because of a suspicious lesion which turned out to be tubulovillous
      adenoma on histological analysis. Eight months after the surgery, a mass
      infiltrating the mesentery was found and biopsy revealed IgG4-RD. INTERVENTIONS:
      Both the orbital inflammation and abdominal mass infiltrating the mesentery were
      responsive to steroids and rituximab administered to treat IgG4-RD. OUTCOMES: In
      the course of IgG4-RD, the patient developed bilateral optic perineuritis,
      causing bilateral visual loss. Colon cancer with synchronous multiple liver
      metastases was found 1 year after rituximab treatment. LESSONS: This case raises
      the possibility of IgG4-RD being a paraneoplastic syndrome in some patients.
      Cancer screening should probably be performed in some elderly patients diagnosed
      with IgG4-RD.

PMID- 30278492
TI  - ST segment elevation myocardial infarction (STEMI) patients are more likely to
      achieve lipid-lowering treatment goals: A retrospective analysis of patients
      presenting with first acute coronary syndromes.
AB  - Statin nonadherence or discontinuation is associated with increased
      cardiovascular events. Many factors related to the physicians or the patients are
      influential in this. We aimed to compare the compliance with statin therapy
      between the patients who first presented with ST-elevation myocardial infarction
      (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina
      pectoris (UA) based on the target achievement according to the current
      dyslipidemia guidelines.We retrospectively acquired all the information about
      demographic characteristics, in-hospital revascularization procedures, prescribed
      treatments, and index and up to 6-month follow-up laboratory results of the first
      acute coronary syndrome patients. Acute coronary syndrome patients were divided
      into 3 groups as STEMI, NSTEMI, and UA.The STEMI group consisted of 260 patients,
      NSTEMI group consisted of 560 patients, and UA group consisted of 206 patients.
      Seventy-six percent of patients underwent percutaneous coronary interventions,
      18.3% were managed medically, and 5.7% were referred for coronary artery bypass
      grafting. There was a significant decrease in low-density lipoprotein-cholesterol
      (LDL-C) values with the statin treatment at the follow-up in all 3 groups (for
      all P < .001). In the STEMI group, the percentage of those achieving the target
      LDL-C level was significantly higher than those who did not achieve the target
      according to both The American College of Cardiology/American Heart Association
      (ACC/AHA) and European Society of Cardiology dyslipidemia guidelines. The LDL-C
      target achievement rates were also higher in the STEMI group than in the NSTEMI
      and UA groups.Our study concluded that statin treatment goals were more attained
      in STEMI patients than NSTEMI and UA. All physicians should encourage lifelong
      intensive statin treatment in UA and NSTEMI patients such as STEMI patients.

PMID- 30278493
TI  - Early postoperative outcomes of surgery for intestinal perforation in NEC based
      on intestinal location of disease.
AB  - Current surgical strategies for necrotizing enterocolitis (NEC) include primary
      drainage, resection with enterostomies, and primary anastomosis. There is
      considerable controversy regarding the preferable surgical management of NEC. We
      sought to investigate whether the surgical outcomes of newborns with NEC
      undergoing exploratory laparotomy differed according to the location of the
      disease site.A total of 204 patients with NEC following laparotomy between July
      2007 and May 2017 were retrospectively reviewed. Clinical outcomes, including
      mortality, neonatal intensive care unit (NICU) length of stay and complications,
      were evaluated based on the type of surgical operation.Enterostomy creation or
      primary anastomosis was performed in 98 patients, and 106 cases underwent
      laparotomy and simple drainage because of panintestinal involvement with near
      total intestinal compromise or no perforation. The ileum was the most commonly
      affected location (n = 170, 83.3%). Patients who had undergone a simple drainage
      procedure experienced less blood loss (P = .023) and a shorter procedure time (P
      = .061), although no statistical significance was attained. Infants with bowel
      anastomosis or ostomy had significantly shorter times to beginning enteral feeds
      (P = .023) and times on mechanical ventilation (P = .011) compared with infants
      who had undergone drainage (Student's t test). The mean NICU length of stay (P =
      .088) was longer for the patients with drainage, although the difference did not
      attain significant. No difference in the overall mortality rate was detected
      between the 2 groups (P = .10).The postoperative outcomes in newborns undergoing
      laparotomy were associated with the surgical type, which was determined by
      disease location in the bowel.

PMID- 30278494
TI  - Effects of the attenuation correction and reconstruction method parameters on
      conventional cardiac dynamic SPECT.
AB  - Nuclear cardiology has not witnessed development of new tracers or hardware for
      many years. Hence there is a need for the development of improvised techniques.
      Dynamic cardiac single photon emission computed tomography (SPECT) is one such
      technique that has a potential to overcome the limitations of conventional
      myocardial SPECT including the absolute quantification of blood flow. The main
      goal of this study is to evaluate the effect of attenuation correction (AC) on
      estimation of the washout parameters extracted from dynamic SPECT using a
      conventional protocol. The effect of the postprocessing on quantitative
      evaluation of dynamic SPECT is also assessed.A physical phantom was employed to
      physically simulate the dynamic behavior of a heart in the thorax. Using a dual
      detector SPECT system, 180 degrees  tomographic data in every 90 seconds were
      acquired. The SPECT data were reconstructed using ordered subset expectation
      maximization (OSEM) method while different iterations and a Butterworth filter
      with different cut-off frequencies were applied. Estimated washout parameter of
      the time activity curves (TACs) was compared with applying AC or without
      it.Results show that AC can improve the bias of computed washout parameter in
      normal regions (average bias reduction in normal ROI: 7%). Moreover, the
      postreconstruction filtering and reducing the number of iterations in
      reconstructing phase can reduce the variance of the computed washout values in
      normal regions (from 3.99% for cut-off frequency 0.5 cycle/cm and 32 times update
      in OSEM to 2.05% for cut-off frequency 0.35 cycle/cm and 16 times update in
      OSEM). They also reduce the actual size of the defect region (13% reduction in
      defect extent for above change in reconstruction parameters).According to the
      results, the AC and postprocessing filtration can directly affect the standard
      deviation of washout value acquired by cardiac dynamic SPECT. These parameters
      also showed a direct effect on the defect extent in final results. The study
      showed that the AC may partly improve the bias of calculated normal washout
      value. The effect of attenuation correction on the defective washout value could
      not be answered comprehensively in this paper.

PMID- 30278496
TI  - Histopathologic features of alcoholic cardiomyopathy compared with idiopathic
      dilated cardiomyopathy.
AB  - BACKGROUND: The histologic difference between alcoholic cardiomyopathy (ACM) and
      idiopathic dilated cardiomyopathy (IDCM) is unclear. The present study aimed to
      identify the quantitative pathologic features of ACM compared with IDCM. METHODS:
      Specimens from 6 regions (anterior left ventricle [LV], lateral LV, inferior LV,
      interventricular septum [IVS], anterior right ventricle [RV], and inferior RV)
      were sampled from each explanted heart. Specimens from 4 healthy donor hearts
      were obtained as normal control. Tissues were sectioned and Masson trichrome
      stained. Histomorphometry was performed to evaluate the amount of myocyte,
      fibrosis, fatty tissue, and interstitium by Image-Pro Plus 6.0 (Media
      Cybernetics). RESULTS: A total of 408 specimens were obtained from 34 ACMs and 34
      IDCMs; 8 specimens were obtained from 4 healthy donor hearts. Compared to healthy
      donor hearts, we observed an increase in fibrosis which replaces myocytes in
      myocardium of end-stage cardiomyopathy. The overall myocyte ratio in myocardium
      was 69.5 +/- 8.7% in ACM vs 71.9 +/- 7.4% in IDCM (P < .05). The percentage of
      interstitium was 10.8 +/- 4.8% in ACM vs 9.2 +/- 6.2% in IDCM (P < .05). A
      significant difference of fibrosis, fatty tissue was not discovered. Moreover,
      the myocyte area was 65.37 +/- 11.8% in ACM LV vs 70.03 +/- 9.0% in IDCM LV (P <
      .001). CONCLUSION: We described histologic characteristics in ACM and IDCM. There
      might be a quantitative difference of myocyte, interstitium in myocardium between
      ACM and IDCM, especially in LV. No difference was found in the percentage of
      fibrosis between the 2 groups.

PMID- 30278495
TI  - The effect of dexmedetomidine in coracoid approach brachial plexus block under
      dual stimulation.
AB  - BACKGROUND: Coracoid approach brachial plexus block (CABPB) is safe and effective
      for clinical anesthesia and analgesia. Dual stimulation can enhance the block
      effect of CABPB when using nerve stimulator. Dexmedetomidine is a highly
      selective alpha-adrenoceptor agonist and it can prolong the duration of
      anesthesia when it is added into local anesthetics. The aim of this study was to
      assess the effects of dexmedetomidine on the duration of anesthesia and the
      effective postoperative analgesia time when it was mixed with ropivacaine for
      CABPB under dual stimulation. METHODS: A total of 60 patients were randomly
      assigned into 2 groups (groups D and C), 30 patients in each group. CABPB were
      guided by nerve stimulator under dual stimulation. Each patient received 40 mL of
      0.375% ropivacaine (group C), or 40 mL of 0.375% ropivacaine mixed with 1 MUg/kg
      dexmedetomidine (group D). The duration of anesthesia, the effective
      postoperative analgesia time, sensory and motor block onset time, visual analog
      scale (VAS), and the cumulative dose of rescue tramadol were recorded. RESULTS:
      Twenty-eight patients in each group were analyzed. The duration of anesthesia was
      longer in group D as compared with group C (759 vs 634 minutes, P < .05) and the
      effective postoperative analgesia time was longer in group D as compared with
      group C (986 vs 789 minutes, P < .05) too. The onset time of sensory and motor
      blocks were not significantly different between the 2 groups (P > .05). The VAS
      was similar in the 2 groups at 6 and 12 hours after block (P > .05), but it was
      lower in group D at 24 hours after block as compared to group C (P < .05). The
      cumulative dose of rescue tramadol during the first 48 hours postoperative period
      was significantly lower in group D as compared to group C (P < .05). No
      significant changes were observed in vital signs in either group. CONCLUSION: The
      addition of 1 MUg/kg dexmedetomidine to ropivacaine extends the duration of
      anesthesia and the effective postoperative analgesia time for CABPB under dual
      stimulation. The VAS at 24 hours after block and the demand for rescue tramadol
      during the first 48 hours postoperative period are lower as well without side
      effects in the study group.(Registered in ClinicalTrials.gov id. NCT02961361).

PMID- 30278497
TI  - Laparoscopic segmental resection of the rectum for upper rectal intussusception
      caused by a giant rectal lipoma: A case report.
AB  - RATIONALE: Colonic lipomas are rare benign tumours, usually without any symptoms,
      and most occur in the caecum and ascending colon. We describe a patient with
      upper rectal intussusception caused by a giant rectal lipoma; no similar report
      of this type of case has been published. PATIENT CONCERNS: We report the case of
      a patient who suffered from repeated bloody stools. A wide pedicle polyp (size,
      6.5 * 4.5 * 3.5 cm) was detected at the 15th centimetre of the anal canal via an
      electronic colonoscope. At the initial part of the rectum, intussusception caused
      by a 6.5-cm fat-density mass was observed via abdominal contrast-enhanced
      computed tomography. DIAGNOSIS: Upper rectal intussusception caused by a giant
      rectal lipoma. INTERVENTIONS: Due to the large size of the polyp, an endoscopic
      polypectomy could not be performed. We performed laparoscopic segmental resection
      of the rectum (with preservation of the left colic artery [LCA]). OUTCOMES: The
      patient was discharged on the 7th postoperative day without any complications,
      was monitored on a regular basis at our outpatient department and was free of
      symptoms at a 3-month follow-up visit. LESSONS: Laparoscopic segmental resection
      of the rectum with LCA preservation is safe and feasible for the treatment of
      upper rectal intussusception caused by a giant rectal lipoma.

PMID- 30278498
TI  - Treatment outcomes of patients with non-bacteremic pneumonia caused by
      extensively drug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii
      complex isolates: Is there any benefit of adding tigecycline to aerosolized
      colistimethate sodium?
AB  - Few therapeutic options exist for various infections caused by extensively drug
      resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (XDR-Acb) complex
      isolates, including pneumonia. This study investigated the clinical efficacy
      between aerosolized colistimethate sodium (AS-CMS, 2 million units thrice a day)
      treatment alone or in combination with standard-dose tigecycline (TGC) in
      patients with non-bacteremic pneumonia due to XDR-Acb, and explored the factors
      influencing patients' 30-day mortality.A 1:1 case (n = 106; receiving TGC plus AS
      CMS) control (receiving AS-CMS alone with matching scores) observational study
      was conducted among adult patients with non-bacteremic XDR-Acb complex pneumonia
      in a Taiwanese medical center from January 2014 through December 2016. The
      clinically relevant data were retrospectively recorded. The primary endpoint was
      30-day case fatality. Secondary endpoints investigated that if the co
      morbidities, XDR-A. baumannii as a pneumonic pathogen, therapy-related factors,
      or airway colonization with colistin-resistant Acb negatively influenced the 14
      day clinical condition of enrolled patients.A higher 30-day mortality rate was
      noted among the group receiving combination therapy (34.0% vs 22.6%; P = .17).
      The >=7-day AS-CMS therapy successfully eradicated > 90% of airway XDR-Acb
      isolates. Nevertheless, follow-up sputum specimens from 10 (6.4% [10/156])
      patients were colonized with colistin-resistant Acb isolates. After the
      conditional factors were adjusted by multivariate logistic analysis, the only
      factor independently predicting the 30-day case-fatality was the failure of
      treating XDR-Acb pneumonia at 14 days (adjusted odds ratio [aOR] = 38.2; 95%
      confidence interval [CI] = 9.96-142.29; P < .001). Cox proportional regression
      analysis found that chronic obstructive pulmonary disease (COPD) (adjusted hazard
      ratio [aHR] = 2.08; 95% CI = 1.05-4.10; P = .035), chronic renal failure (aHR =
      3.00; 95% CI = 1.52-5.90; P = .002), non-invasive ventilation use (aHR = 2.68;
      95% CI = 1.37-5.25; P = .004), and lack of TGC therapy (aHR = 0.52; 95% CI = 0.27
      1.00; P = .049) adversely influenced the 14-day clinical outcomes. Conversely,
      the emergence of colistin-resistant Acb isolates in the follow-up sputum samples
      was not statistically significantly associated with curing or improving XDR-Acb
      pneumonia.In conclusion, aggressive pulmonary hygiene care, the addition of TGC,
      and corticosteroid dose tapering were beneficial in improving the 14-day
      patients' outcomes.

PMID- 30278499
TI  - Epidemiological trends of fatal pediatric trauma: A single-center study.
AB  - To evaluate the potential risk factors which increase the incidence of post
      trauma complications and mortality in pediatric population.A retrospective cohort
      study was conducted on patients below 18 years of age with a fatal outcome who
      were admitted to an Indian level-1 trauma center between January 2013 and
      December 2015. This cohort was analyzed to determine the demographics, injury
      mechanism, injury severity, microbiological profile, and cause of death.In total,
      320 pediatric patients with a fatal outcome were studied which showed male
      preponderance (71.56%). The median age of the patients was 11 years (range, 0.14
      18 years). Median duration of stay was 1 day (range, 0-183 days). Fall and road
      traffic accidents were the common mechanisms of trauma while the main injury was
      head injury. In total, 857 clinical samples were received from 56 patients. The
      clinical samples from 35 (10.94%) patients were culture positive. Culture-proven
      infections were significantly correlated with the length of hospital stay (P =
      .001). In total, 212 organisms were isolated from 193 positive samples of which
      gram-negative bacteria were predominant (89.15%). The most common gram-positive
      bacterial isolate was Staphylococcus aureus (12, 52.17%), while Acinetobacter
      baumannii (66, 34.92%) was the most prevalent gram-negative bacterial isolate
      followed by Pseudomonas spp. (36, 19.05%), Klebsiella pneumoniae (35, 18.52%),
      and Escherichia coli (16, 8.47%). Up to 100% multidrug resistance was seen in
      both gram-positive and gram-negative bacterial isolates. The first 24 hours after
      trauma were the deadliest for our patients. Head/central nervous system injury
      was the primary cause of disabilities and early death whereas infection
      attributed to prolonged hospital stay.From these observations we concluded that
      management of pediatric trauma requires expert, multidisciplinary, and timely
      interventions. Moreover, nosocomial infections with multidrug resistant gram
      negative bacteria challenges the accepted tenets of trauma care affecting the
      outcome of the pediatric population. Early identification of such high-risk
      patients' infection may facilitate early intervention. Thus, many deaths in
      pediatric group are preventable.

PMID- 30278500
TI  - Identification of volume parameters monitored with a noninvasive ultrasonic
      cardiac output monitor for predicting fluid responsiveness in children after
      congenital heart disease surgery.
AB  - No previous study has used an ultrasonic cardiac output monitor (USCOM) to assess
      volume parameters, such as stroke volume variation (SVV), in order to predict the
      volume status and fluid responsivenes in children after congenital heart disease
      (CHD) surgery. The present prospective trial aimed to investigate the ability of
      SVV and corrected flow time (FTc), which were assessed with a USCOM, for
      predicting fluid responsiveness in children after CHD surgery.The study included
      60 children who underwent elective CHD surgery. Data were collected after
      elective CHD surgery. After arrival at PICU, the continuous invasive blood
      pressure was monitored. Once the blood pressure (BP) decreased to the minimum
      value, 6% hydroxyethyl starch (130/0.4) was administered (10 mL/kg) over 30
      minutes for volume expansion (VE). The USCOM was used to monitor the heart rate,
      central venous pressure, stroke volume index (SVI), cardiac index, SVV, FTc of
      the children before and after VE. Additionally, the SVI change (DeltaSVI) was
      calculated, and the inotropic score (IS) was determined. Children with a DeltaSVI
      >=15% were considered responders, while the others were considered nonresponders.
      The children were also divided into IS <=10 and IS >10 groups.Of the 60 children,
      32 were responders and 28 were nonresponders. We found that only SVV was
      significantly correlated with DeltaSVI (r = 0.42, P < .01). SVV could predict
      fluid responsiveness after surgery (area under the curve [AUC]: 0.776, P < .01),
      and the optimal threshold was 17.04% (sensitivity, 84.4%; specificity, 60.7%).
      Additionally, the SVV AUC was higher in the IS >10 group than in the IS <=10
      group (0.81 vs 0.73).SVV measured with a USCOM can be used to predict fluid
      responsiveness after CHD surgery in children. Additionally, the accuracy of SVV
      for predicting fluid responsiveness might be higher among patients with an IS >10
      than among those with an IS <=10.

PMID- 30278501
TI  - The impact of previous abdominal surgery on clinical characteristics and
      prognosis of pyogenic liver abscess: A 10-year retrospective study of 392
      patients.
AB  - Many pyogenic liver abscess (PLA) patients underwent abdominal surgery before.
      However, little is known about the impact of previous abdominal surgery on the
      clinical characteristics and prognosis of PLA.The clinical data of 392 adult PLA
      patients who received treatment at our hospital from January 1, 2007 to December
      31, 2016 were collected. The demographic data, cause, comorbidities, surgery
      history, clinical features, laboratory results, imaging findings, microbiological
      characteristics, choices of treatment, and clinical outcomes were analyzed.In
      all, 177 PLA patients (45.2%) underwent abdominal surgery before. The median time
      for the occurrence of PLA after the most recent abdominal surgery was 2.0
      (interquartile range 0.25, 6.0) years. PLA patients with a previous abdominal
      surgery history were more likely to have underlying diseases and presented with
      more abnormal laboratory values. Klebsiella pneumonia and Escherichia coli were
      the most common pathogens. Previous abdominal surgery appeared to increase the
      incidence of E coli. More PLA patients without a previous abdominal surgery
      history required surgical drainage. However, there were no differences in PLA
      related complications, days required for temperature normalization, and length of
      hospital stay between the 2 groups.Because a large number of PLA patients had a
      history of abdominal surgery, and proper screening should be performed for
      patients with any suspicion of a liver abscess after abdominal surgery. Despite
      the differences in the coexisting conditions, clinical and microbiological
      characteristics between PLA patients with and without a previous abdominal
      surgery history, the overall short-term outcomes were comparable.

PMID- 30278502
TI  - Association of miRNA-146a rs2910164 and miRNA-196 rs11614913 polymorphisms in
      patients with ulcerative colitis: A meta-analysis and review.
AB  - BACKGROUND: It has been reported that the single nucleotide polymorphisms (SNPs)
      miRNA-196 (miR-196) rs11614913 and miRNA-146a (miR-146a) rs2910164 are related to
      susceptibility to ulcerative colitis (UC). Because the previously reported
      results have been mixed and uncertain, the aim of this study was to perform a
      meta-analysis and review to assess the relationship between these 2 SNPs and UC
      risk. METHODS: In this analysis, 5 studies involving 1023 cases and 1769 controls
      for miR-196 rs11614913 and 4 studies involving 827 cases and 1451 controls for
      miR-146 rs2910164 were included. Odds ratios (ORs) and 95% confidence intervals
      (95% CIs) were used to pool the effect size. RESULTS: A decreased risk of UC was
      identified in homozygote comparison (GG vs CC: OR = 0.69, 95% CI: 0.52-0.93, P =
      .02), recessive comparison (GG vs CG + CC: OR = 0.74, 95% CI: 0.59-0.92, P =
      .007), and dominant comparison (GG + CG vs CC: OR = 0.79, 95% CI: 0.65-0.97, P =
      .02) of miR-146 rs2910164 in Asian but not Caucasian population. No evidence of
      an association was shown between the rs11614913 polymorphism and UC risk in
      allelic, heterozygote, homozygote, recessive, and dominant models in both
      Caucasian and Asian populations (P > .05). CONCLUSIONS: MiR-146 rs2910164, but
      not miR-196 rs11614913, was associated with a decreased risk of UC in Asian
      population. However, the results should be treated with caution because of the
      limited sample size and heterogeneity. Well-designed studies with large sample
      sizes and more ethnic groups are needed to validate the risks identified in the
      current meta-analysis and review.

PMID- 30278503
TI  - Prosthesis satisfaction in lower limb amputees: A systematic review of associated
      factors and questionnaires.
AB  - BACKGROUND: Factors influencing patient satisfaction with a transtibial
      prosthesis have been studied fragmentarily. The aims of this systematic review
      were to review the literature regarding factors of influence on patient
      satisfaction with a transtibial prosthesis, to report satisfaction scores, to
      present an overview of questionnaires used to assess satisfaction and examine how
      these questionnaires operationalize satisfaction. METHODS: A literature search
      was performed in PubMed, Embase, PsycInfo, CINAHL, Cochrane, and Web of Knowledge
      databases up to February 2018 to identify relevant studies. RESULTS: Twelve of
      1832 studies met the inclusion criteria. Sample sizes ranged from 14 to 581
      participants, mean age ranged from 18 to 70 years, and time since amputation
      ranged from 3 to 39 years. Seven questionnaires assessed different aspects of
      satisfaction. Patient satisfaction was influenced by appearance, properties, fit,
      and use of the prosthesis, as well as aspects of the residual limb. These
      influencing factors were not relevant for all amputee patients and were related
      to gender, etiology, liner use, and level of amputation. No single factor was
      found to significantly influence satisfaction or dissatisfaction. Significant
      associations were found between satisfaction and gender, etiology, liner use, and
      level of amputation. CONCLUSION: Relevance of certain factors for satisfaction
      was related to specific amputee patient groups. Questionnaires assessing
      satisfaction use different operationalizations, making comparisons between
      studies difficult.

PMID- 30278504
TI  - Can Vulnerable Elders Survey-13 predict the impact of frailty on chemotherapy in
      elderly patients with gynaecological malignancies?
AB  - The management of gynaecological cancers in elderly women and high-risk patients
      is an even more relevant issue, because the increase in longevity and
      comorbidities. The assumption of frailty based on age alone may lead to
      inadequate and inappropriate treatment and frailty assessment is recommended. The
      aim of this study was to assess if Vulnerable Elders Survey-13 (VES-13), as
      indicator of frailty, can predict the toxicity of chemotherapy in gynaecological
      cancers.VES-13 was administered to patients aged >= 70 years with ovarian,
      endometrial and cervical cancers who underwent chemotherapy from 2010 to
      2016.Eighty-four patients aged >= 70 years (mean age 74.6) were included, 36
      patients (42.9%) resulted vulnerable (score >= 3). Thrombocytopenia and anaemia
      were more prevalent in the vulnerable subjects (81.3% versus 18.7%, P = .0005,
      and 81.8% versus 18.2%, P = .005, respectively), while neutropenia was similar
      between the 2 groups. Vulnerable women had higher risk of non-haematological
      toxicities. Most of the patients (77.4%) completed chemotherapy, but dose
      reductions and discontinuations were more common in the vulnerable group (66.7%
      versus 33.3%, P = .07 and 68.4% versus 31.6%, P = .01, respectively).To our
      knowledge, this is the first study to evaluate VES-13 exclusively in elderly
      women with gynaecological cancers. VES-13 may be useful to stratify this category
      of patients according to vulnerability in order to identify women at risk of
      toxicity and to prevent complications induced by chemotherapy.

PMID- 30278506
TI  - Trisomy 22 with long spina bifida occulta: A case report.
AB  - INTRODUCTION: Complete non-mosaic trisomy 22 is a fatal chromosomal disorder that
      only few fetuses can survive over 12 weeks as reported. Prenatal sonographic
      findings combined with postnatal or postmortem discoveries showed characteristic
      multi-systematic anomalies. PATIENT CONCERNS: The unborn baby of a 35-year-old
      pregnant woman was found to have several anomalies during a prenatal sonographic
      scan, including intrauterine growth retardation, ventricular septal defect, flat
      facial profile, and unclear bilateral kidney structures. DIAGNOSES: The fetus was
      diagnosed as having complete non-mosaic trisomy 22 by chromosomal analysis.
      INTERVENTIONS: The pregnancy was terminated at 24 weeks, and autopsy was
      permitted. OUTCOMES: Postmortem examinations revealed additional long-sectional
      spina bifida occulta and imperforate anus. CONCLUSIONS: This was the first time a
      case of spinal cord defect was reported in trisomy 22 fetuses. More attention
      should be paid to the spinal cord during sonographic examinations in trisomy 22
      fetuses.

PMID- 30278505
TI  - Matrix metalloproteinase-2 gene polymorphisms are associated with ischemic stroke
      in a Hainan population.
AB  - Ischemic stroke is a complex vascular disease, which has become 1 of the major
      causes of morbidity and mortality worldwide. More and more data showed that
      matrix metalloproteinases (MMPs), in particular, MMP-2 are deleterious after
      ischaemic stroke. This study investigated the relationship between MMP-2 and
      stroke risk in the Southern Chinese population.We evaluated single nucleotide
      polymorphisms (SNP) of MMP-2 in stroke patients in an association study using a
      case-control design. Six SNPs of MMP2 were selected and genotyped by Agena
      MassARRAY. SNPStats, Haploview was used to analyze genetic data.Two SNPs in the
      MMP-2 gene were significantly associated with stroke risk.For rs1132896 (C versus
      G allele), the C allele was significantly reduced stroke risk (OR = 0.56, 95%
      confidence intervals [95% CI] = 0.39-0.81, P = .002). The effect of the T allele
      of rs243849 was IS risk according to an additive genetic model (OR = 0.67, 95% CI
      = 0.47-0.96, P = .028). We did not found any strong linkage between the six SNPs
      (rs1132896, rs1053605, rs243849, rs243847, rs243832, rs7201)The results presented
      strongly indicate that MMP-2 genetic variants are an important mediator of stroke
      risk.

PMID- 30278507
TI  - Positron emission tomography/computed tomography manifestations of primary
      hepatic myxoid liposarcoma: A case report.
AB  - RATIONALE: Computed tomography (CT) and magnetic resonance imaging (MRI) are
      conventional used to evaluate liver tumors. Detection of fat component is
      considered an important clue to the imaging diagnosis of hepatic myxoid
      liposarcoma. However, the positron emission tomography (PET)/CT report of hepatic
      myxoid liposarcoma is scarce, and the metabolic characteristics of primary
      hepatic myxoid liposarcoma are still unknown. PATIENT CONCERNS: In this report,
      we report the PET/CT manifestations of a rare case of primary hepatic myxoid
      liposarcoma that was confirmed by pathologic examination. A 29-year-old male
      patient presented with a nodule adjacent to the umbilicus that had been present
      for 2 weeks. PET/CT showed a hypoattenuating mass with moderate uptake (maximum
      standardized uptake value [SUVmax] 1.9), except for a slightly hyperattenuating
      focal area with intense uptake (SUVmax 3.1). DIAGNOSES: The final pathologic
      diagnosis was confirmed, by means of laparotomy, to be a primary hepatic myxoid
      liposarcoma with multiple extrahepatic metastases. INTERVENTIONS: The lesions in
      the left liver and periumbilical abdominal wall were punctured. During the
      laparotomy, hepatic malignant tumors were confirmed and metastasized widely in
      the abdominal cavity. OUTCOMES: An abdominal CT performed 4 months after initial
      presentation showed extensive metastasis. LESSONS: Primary hepatic myxoid
      liposarcoma may manifest as moderate metabolism with less fat on PET/CT. PET/CT
      is not only valuable in reflecting the round cell component of hepatic myxoid
      liposarcoma, but also in estimating its origin.

PMID- 30278508
TI  - Multiple myeloma with pathologically proven skull plasmacytoma after a mild head
      injury: Case report.
AB  - RATIONALE: MM is a malignant tumor originating from the plasma cells of the bone
      marrow. Central nervous system myelomatosis is very rare and may be a
      complication of MM. PATIENT CONCERNS: A 60-year-old man presented with a slowly
      growing soft mass at his right frontal scalp after a mild head injury 6 months
      ago. DIAGNOSES: Neuroradiological examinations revealed a solid intracranial
      extracranial mass with an osteolytic lesion in the skull. Histopathological
      examination showed skull plasmacytoma, and postoperative examinations revealed
      multiple myeloma. INTERVENTIONS: The tumor was completely removed and the skull
      defect repaired with the titanium mesh. Then, chemotherapy was initiated after
      surgery with bortezomib and dexamethasone. OUTCOMES: The patient received eight
      chemotherapies within one year after surgery. LESSONS: Despite a history of head
      injury, a differential diagnosis should be kept in mind during the diagnosis of
      solid intracranial-extracranial masses, especially in the presence of osteolytic
      skull at the lesioned site.

PMID- 30278509
TI  - Face-neck lifting and ancillary procedures: A series of 203 cases.
AB  - Various methods and ancillary procedures have been defined in the era of face
      lifting surgery.The purpose of this study was to evaluate the esthetic outcomes
      of our face-neck cases and the importance of adding ancillary procedures based on
      individual assessment.We conducted a retrospective review of 203 face-neck cases,
      basically following the endoscopic and open principles of Vasconez. The ancillary
      procedures added in selected cases included genioplasty, augmentation with
      autologous facial superficial fascial tissue or fat injections, upper lip
      shortening, perioral dermabrasion, ear lobe reduction, buccal fat reduction,
      mentum lifting, and upper orbital rim shaving. Complications, postoperative
      follow-up, esthetic outcomes, and contribution of the ancillary procedures were
      recorded.Our esthetic face complication rates were comparable to those of
      previous studies and included chemosis, hematoma, cyst on the eyelid suture line,
      skin sloughing, scar abnormalities (hypertrophic scar and widespread scar),
      pseudoparalysis of the marginal mandibular branch, temporary hypoesthesia of the
      forehead, irregularity of the glabella after endoscopy, and asymmetry. We did not
      observe any comorbidity owing to genioplasty and augmentation with autologous
      tissue except for a case with infection after fat injection.More improvement can
      be obtained with careful planning of ancillary procedures in face-neck lifting
      surgery.

PMID- 30278510
TI  - Non-alpha-fetoprotein-producing adrenal hepatoid adenocarcinoma: A case report
      and literature review.
AB  - RATIONALE: Adrenal hepatoid adenocarcinoma typically secretes alpha-fetoprotein
      (AFP). Here, we report a case of non-AFP-producing adrenal hepatoid
      adenocarcinoma. Next-generation sequencing (NGS) was conducted to identify gene
      mutations. PATIENT CONCERNS: A 64-year-old man presented with mild back pain and
      unexplained weight loss for 3 months. DIAGNOSES: Contrast-enhanced magnetic
      resonance imaging (MRI) showed a mass (9.9 * 9.7 * 9.1 mm) above the upper pole
      of the left kidney. The left renal artery and vein were compressed. The tumor was
      positive for CK8/18, CK19, CK7, hepatocyte marker (Hepatocyte), and Hep Par 1,
      but negative for AFP. Plasma AFP was 2.75 ng/mL (normal range: 0-7 ng/mL). NGS
      revealed mutations of the following genes: ATM, CDKN2A, EGFR, STK11, TP53, BIM,
      and MLH1. A diagnosis of adrenal hepatoid adenocarcinoma was established.
      INTERVENTIONS: The treatment included 4 cycles of the mFOLFOX6 regimen
      (oxaliplatin, leucovorin, and fluorouracil), transcatheter arterial
      chemoembolization, and apatinib. OUTCOMES: The patient died 9 months after the
      diagnosis. LESSONS: This case highlights the importance of thorough clinical,
      radiological, and immunohistochemical investigation for suspected adrenal
      hepatoid adenocarcinoma. Metastasis from other primary tumors should be ruled
      out. Furthermore, AFP is not necessarily elevated in adrenal hepatoid
      adenocarcinoma. NGS could be helpful in establishing the diagnosis and selecting
      treatments.

PMID- 30278511
TI  - Red blood cell distribution width-to-platelet ratio as a disease activity
      associated factor in systemic lupus erythematosus.
AB  - BACKGROUND: Although different clinical and experimental parameters have been
      used to estimate disease activity in systemic lupus erythematosus (SLE) patients,
      the relationship between red blood cell distribution width-to-platelet ratio
      (RPR) and disease activity in SLE has not been previously illuminated. Therefore,
      the aim of this study was to investigate the association between RPR levels and
      disease activity in SLE. METHODS: This study enrolled 105 SLE patients and 105
      healthy subjects. We divided the patients into 2 groups using the SLE Disease
      Activity Index (SLEDAI) 2000. Group 1 included patients with SLEDAI score <=9
      (mild disease activity group) and group 2 with SLEDAI >9 (severe disease activity
      group). Correlations between RPR and disease activity were then analyzed. A
      subgroup follow-up analysis of 93 patients was conducted to explore the effect of
      SLE-related glucocorticoid therapy. RESULTS: The PLR and RPR values of SLE
      patients were significantly higher compared with the controls (both P < .001),
      whereas mean platelet volume was decreased (P < .05). The RPR level was found to
      be positively correlated with SLEDAI (r = 0.368, P < .001) and erythrocyte
      sedimentation rate (r = 0.313, P = .027). According to the receiver-operating
      characteristic (ROC) curve, the optimal cut-off value for predicting SLE using
      RPR was 0.073, and the area under ROC curve was 0.817. RPR level was correlated
      with clinical disease activity in SLE, and its value was normalized after
      treatment. CONCLUSION: RPR may be a useful measurement for the assessment of
      disease activity in SLE patients.

PMID- 30278512
TI  - Modified enhanced recovery after surgery protocols are beneficial for
      postoperative recovery for patients undergoing emergency surgery for obstructive
      colorectal cancer: A propensity score matching analysis.
AB  - Enhanced recovery after surgery (ERAS) is acknowledged to reduce perioperative
      stress in several surgical diseases. Here, we investigated whether modified ERAS
      is associated with beneficial effects in the setting of emergency colorectal
      surgery.We retrospectively evaluated the medical records of 839 consecutive
      patients with obstructive colorectal cancer undergoing surgical intervention at 4
      institutes. Among them, 356 cases were managed with a multidisciplinary team
      approach to care (modified ERAS protocols), and the remaining 483 cases were
      treated based on traditional protocols. According to modified ERAS or traditional
      care, propensity score (PS) matching was performed to adjust biases in patient
      selection. The primary outcome was gastrointestinal function recovery. Secondary
      outcomes included postoperative complications and length of hospital
      stay.Modified ERAS was associated with postoperative gastrointestinal function
      recovery, including time to first flatus (P = .002), first defecation (P = .008),
      and prolonged ileus (P = .016). According to the Clavien-Dindo classification,
      fewer total episodes of grade II or higher postoperative complications were
      observed in patients cared for with modified ERAS than in patients with
      traditional care (P = .002). Median (interquartile range) postoperative hospital
      stay in the modified ERAS group was 6 (3-22) days versus 9 (7-27) days in the
      traditional care group (P < .001). Furthermore, the interval from operation to
      postoperative chemotherapy (d) was significantly shorter in the modified ERAS
      group (35.6 +/- 11.5 vs 47.6 +/- 23.8, P < .001).The modified ERAS was safe and
      associated with clinical benefits, including fast recovery of bowel function,
      reduced postoperative complications, and shorter hospital stay for patients with
      obstructive colorectal cancer.

PMID- 30278513
TI  - A multiple myeloma that progressed as type I cryoglobulinemia with skin ulcers
      and foot necrosis: A case report.
AB  - RATIONALE: Type I cryoglobulinemia is a rare and life-threatening condition. It
      occurs mainly in B-cell lymphoproliferative disorder. In almost half of the
      patients, type I cryoglobulinemia is characterized by severe cutaneous
      involvement. PATIENT CONCERNS: A 71-year-old man comes to our observation because
      of the onset of persistence of paresthesia and painful acrocyanosis in the
      fingers and toes. IgG-k multiple myeloma treated with chemotherapy and radiation
      therapy on the left iliac wing characterized his clinical history. At the
      evaluation of response after the first-line therapy, the patient achieved a very
      good partial response. At the time of progression, the same myelomatous disease
      has taken a typical behavior of cryoglobulinemia. DIAGNOSES: Type I multiple
      myeloma-associated cryoglobulinemia was diagnosed. INTERVENTIONS: The patient
      underwent to an immediate composite therapeutic approach based on prostanoid
      infusion, plasmapheresis along with second-line chemotherapy. OUTCOMES: Despite
      the rapid biochemical response, the ischemia of the feet worsened. Moreover, a
      bacterial infection overlapped. The surgical amputation of both feet was
      necessary. Allowing MM cytoreduction continuation the patient's clinical
      condition became stabilized. LESSONS: Though rare, type I cryoglobulinemia can be
      associated with plasma cell dyscrasias. Any delay in diagnosis and the start of
      therapy can cause worsening of organ damage and endanger the patient's life.
      Therapeutic strategies in these cases should be directed to the underlying
      diseases.

PMID- 30278514
TI  - The effective clinical outcomes of the Gufoni maneuver used to treat 91 vertigo
      patients with apogeotropic direction-changing positional nystagmus (apo-DCPN).
AB  - This study aimed to observe and analyze the effects and outcomes of patients with
      apogeotropic direction-changing positional nystagmus (apo-DCPN) who received
      Gufoni maneuver.A total of 91 patients with positional vertigo admitted to the
      specialized dizziness clinic in Zhejiang Provincial People's Hospital from
      February 2014 to August 2017 were included. The immediate treatment responses to
      the Gufoni maneuver were observed and recorded. The patients in whom the
      treatment was ineffective were followed up for 4 weeks to observe the outcome of
      apo-DCPN.In 21 patients, the apo-DCPN was transformed after Gufoni maneuver, and
      7 patients developed transformation within 4 weeks of follow-up. Spontaneous
      remission of apo-DCPN within the follow-up period was observed in 55 patients who
      were unresponsive to the Gufoni maneuver. The prevalence of migraine was
      significantly higher in the early remission group (P < .05) and the period
      between the initial visit and nystagmus remission was significantly shorter in
      the group of patients with migraine history (P < .05).This study demonstrates
      that the immediate treatment efficacy of the Gufoni maneuver is poor in
      positional vertigo patients with apo-DCPN. We believe that the reason for the low
      efficacy is that the Gufoni maneuver is only effective for some patients with apo
      DCPN type HSC-BPPV. In patients with early spontaneous remission and a history of
      migraine, central positional nystagmus of probable vestibular migraine (VM) or
      benign recurrent vertigo should be considered for the mechanisms of apo-DCPN
      generation.

PMID- 30278515
TI  - Optical tissue clearing in combination with perfusion and immunofluorescence for
      placental vascular imaging.
AB  - Imaging of placental tissues is a difficult task, because of specific for this
      organ complex multicellular and 3D tissue structure. The tissue clearing systems
      (X-CLARITY) system is a valuable tool for the examining the expression of
      molecular pathways in whole tissues and organs, originally developed for brain
      imaging.In the present report, we utilized this technology for the examination of
      placental vasculature and protein expression in perfused human placental
      tissue.The placental tissue was sufficiently cleared with preservation of
      endothelial staining and fluorescent markers, allowing visualization using
      confocal microscopy. The CLARITY method and X-CLARITY system is a valuable tool
      in placental imaging.

PMID- 30278516
TI  - A case report of intrahepatic bile duct confluence anomalies in VACTERL syndrome.
AB  - RATIONALE: The clinical manifestations of VACTERL association include vertebral
      anomalies, anal atresia, congenital heart diseases, tracheoesophageal fistula,
      renal dysplasia, and limb abnormalities. The association of intrahepatic
      anomalies and VACTERL syndrome is a rare coincidence. VACTER syndrome and
      intrahepatic bile drainage anomalies might be genetically related. PATIENT
      CONCERNS: A 12-year-old girl presented with episodic colicky abdominal pain,
      nausea, and vomiting for several years. The individual episodes resolved
      spontaneously within a few days. She had a history of VACTERL syndrome, including
      a butterfly shape of the L3 vertebra, anal atresia, and an atrial septal defect.
      DIAGNOSES: On laboratory findings, abnormal liver function tests included
      elevated total bilirubin, alanine aminotransferase, aspartate aminotransferase,
      and gamma-glutamyltransferase. There was no significant abnormal finding in
      hepatobiliary system sonography except mild gallbladder wall thickening. We
      performed magnetic resonance cholangiopancreatography and demonstrated an
      abnormal intrahepatic bile duct confluence, which showed 3 bile ducts draining
      directly into the neck of the gallbladder. INTERVENTION: Her symptoms related to
      bile reflux during gallbladder contraction. Cholecystectomy with
      choledochojejunostomy was undertaken because segments of the bile drainage were
      intertwined. OUTCOMES: After surgery, her symptoms decreased, but abdominal
      discomfort remained due to uncorrected left intrahepatic anomalies. LESSONS:
      Although hepatobiliary anomalies are not included in VACTERL association
      diagnostic criteria, detailed hepatobiliary work up is needed when
      gastrointestinal symptoms are present in VACTERL association patients.

PMID- 30278517
TI  - The effect of nicotine patches on craving in the brain: A functional MRI study on
      heavy smokers.
AB  - BACKGROUND: Smoking is a common phenomenon and kills over 6 million people every
      year. Many smokers try to quit smoking by using nicotine replacement therapy
      (NRT). Most of the time, relapse occurs in less than six months after finishing
      the program of NRT. We performed a single blinded study in which our aim was to
      figure out what the effect of the nicotine patch is on craving in the brain of
      smokers deprived from smoking. METHODS: Five heavy smokers (Fagerstrom Test for
      Nicotine Dependence >=4) underwent a functional magnetic resonance imaging (fMRI)
      in 4 random conditions: smoking (S); smoking deprivation (SD); SD combined with a
      NP (SD + NP); SD combined with a placebo patch (SD + PP). Visual stimulation
      provoked craving in block design by randomly displaying images of smoking related
      scenes. After image preprocessing, a fixed-effect analysis was performed to
      compare average group activations. The Questionnaire for Smoking Urges (QSU) was
      obtained before and after each scan. RESULTS: The fMRI results showed higher
      activation in areas involved in craving in S compared with SD + NP, SD + PP, and
      SD. In the SD + NP, limbic circuit and attention area were higher activated
      compared with SD and SD + PP. The SD + PP and SD showed higher activation in the
      frontal cortex and limbic system compared with S and SD + NP. Nonsmokers showed
      higher limbic activation compared with SD.The QSU increased significantly after
      the fMRI experiment in S (P = .036).The SD had higher QSU scores compared with
      the S before (P = .002), and also after (P = .022) the fMRI experiment. The NP
      showed lower scores than the SD before the experiment (P = .046). CONCLUSION: The
      fMRI experiment revealed lower activity in areas associated with attention when
      subjects were nicotine deprived (SD + PP and SD). Areas involved with craving
      showed less activity when nicotine is present (S and SD + NP). The QSU showed a
      significant difference between SD and when nicotine is present (S and SD + NP).

PMID- 30278518
TI  - Applying Gini coefficient to evaluate the author research domains associated with
      the ordering of author names: A bibliometric study.
AB  - BACKGROUND: Team science research includes the number of coauthors in
      publications. Many papers have discussed the ordering of author names and the
      contributions of authors to a paper. However, no paper addresses the relation
      between authors' research domains and personal impact factors (PIF) with the
      ordering of author names. We aimed to apply Gini coefficient (GC) to evaluate the
      author research domains associated with the PIF and the ordering of author names
      on academic papers. METHODS: By searching the PubMed database (Pubmed.com), we
      used the keyword "medicine" [journal] and downloaded 10,854 articles published
      from 1969 to 2018. A total number of 7502 articles labeled with complete author's
      countries/areas were included in data analysis. We also proposed a PIF index and
      jointly applied social network analysis (SNA), the GC, and Google Maps to report
      the following data with visual representations: the trend of author collaboration
      in Medicine; the dominant nations and keywords in Medicine; and the author
      research domains in Medicine associated with the PIF and the ordering of author
      names on academic papers. RESULTS: The trend of author collaboration in Medicine
      is slightly declining (= -0.06) based on the number of authors per article. The
      mean number of individuals listed as authors in articles is 7.5. Most first
      authors are from China (3649, 48.64%) and Taiwan (847, 11.29%). The median of GC
      (0.32) and PIF (0.74) for the middle authors are obviously less than those for
      the first (0.53, 2.19) and the last authors (0.42, 2.61). A perfect positive
      linear relation with a large effect exists between GC and PIF because the
      correlation coefficient is 0.68 (>0.50, t = 2.48, n = 9). CONCLUSION: Results
      suggest that the corresponding author is submitting the manuscript to the target
      journal with a core author's academic background and the personal impact factor
      related to the research domain and the journal scope in the future. As such, peer
      reviewers can quickly determine whether the manuscript is a potentially citable
      research paper.

PMID- 30278519
TI  - Predictive values of CSS and NIHSS in the prognosis of patients with acute
      cerebral infarction: A comparative analysis.
AB  - This study aims to investigate the predictive values of the Chinese Stroke Scale
      (CSS) and National Institutes of Health Stroke Scale (NIHSS) in the prognosis of
      patients with acute cerebral infarction.A total of 399 patients with acute
      cerebral infarction were assessed using CSS and NIHSS within 1 day after
      admission. Then, the receiver operating characteristic (ROC) curves were
      established, and the area under the curves of these 2 scoring systems was
      compared.The area under the curve of CSS and NIHSS was 0.796 and 0.794,
      respectively.CSS and NIHSS have good predictive values for the prognosis of
      patients with acute cerebral infarction.

PMID- 30278521
TI  - Association between blood neutrophil-to-lymphocyte ratio and severity of coronary
      artery disease: Evidence from 17 observational studies involving 7017 cases.
AB  - This study aimed to evaluate the association between blood neutrophil-to
      lymphocyte ratio (NLR) and severity of coronary artery disease (CAD), and
      investigate the diagnostic ability and optimal cut-off value of NLR in predicting
      severe stenosis in CAD.A systematic search was conducted in public databases to
      identify all relevant studies. Weighted mean difference (MD) and 95% confidence
      interval (CI) were pooled for continuous univariate data, and odds ratios (OR)
      and 95% CI were calculated for dichotomous multivariate data.Seventeen studies
      were included in this meta-analysis with a total of 7017 CAD cases. For
      continuous univariate data, the cases with the highest stenosis category had a
      significantly higher NLR level than those with lowest stenosis category (MD:
      1.57, 95% CI: 1.06-2.09; n = 17). After further classification according to the
      Gensini or SYNTAX score, the cases with severe stenosis demonstrated a higher NLR
      than those with mild stenosis (MD: 2.33, 95% CI: 1.22-3.43; n = 6) and moderate
      stenosis (MD: 1.92, 95% CI: 0.80-3.04; n = 6). Compared with mild stenosis, NLR
      was also higher in those with moderate-to-severe stenosis (MD: 1.34, 95% CI: 0.77
      1.92; n = 6) and moderate stenosis (MD: 0.52, 95% CI: 0.36-0.68; n = 6). For
      dichotomous multivariate data, high NLR levels were recognized as an independent
      predictor for severe stenosis in CAD (OR: 1.50, 95% CI: 1.32-1.72; n = 11). NLR
      showed a diagnostic ability in predicting severe stenosis in CAD (area under
      receiver operating characteristics [ROC] curve [AUC]: 0.66, 95% CI: 0.64-0.68; n
      = 8), with the cut-off ranging from 1.95 to 3.97. Subgroup analysis and
      sensitivity analysis showed the results were robust. Begg's test detected no
      significant publication biases.This study suggested that high blood NLR was
      associated with the severity of CAD, and it might be useful for predicting severe
      stenosis in CAD.

PMID- 30278520
TI  - Role of Ginkgo biloba extract as an adjunctive treatment of elderly patients with
      depression and on the expression of serum S100B.
AB  - OBJECTIVE: To explore the effect of ginkgo biloba extract (EGb) as an adjunctive
      treatment of elderly patients with depression and the effect on the expression of
      serum S100B. METHODS: 136 elderly patients with depression were divided into EGb
      +  citalopram (Cit) group and Cit group equally. Efficacy was evaluated by
      Hamilton Depression Rating Scale (HAMD). Wisconsin Card Classification Test
      (WCST) was used to evaluate cognitive function. Serum S100B expression was
      measured with ELISA. The relationship of S100B with HAMD, Hamilton Anxiety Scale
      (HAMA) score, and WCST results was evaluated subsequently. RESULTS: The time of
      onset of efficacy was significantly shorter in EGb + Cit group. There were
      significant differences in HAMD and HAMA scores after treatment than before
      treatment between groups (all P < .05). After treatment, total number of WCST
      test, the number of continuous errors and non-persistent errors in both groups
      were less than those before treatment. The correct number and classifications
      number were increased than before treatment. In EGb + Cit group, correct numbers
      and classifications were increased, and the number of persistent errors was
      decreased. After treatment, S100B level was decreased, and S100B levels change in
      EGb + Cit group was greater than in Cit group. Serum S100B level was positively
      correlated with HAMD and HAMA scores before treatment and positively correlated
      with persistent errors number in WCST. CONCLUSION: EGb, as an adjunctive
      treatment, can effectively improve depressive symptoms and reduce expression of
      serum S100B, which is a marker of brain injury, suggesting that EGb restores
      neurologic function during the treatment of depression in elderly patients and
      S100B participates in the therapeutic mechanism. EGb combined with depressive
      drugs plays synergistic role, and the time of onset of efficacy is faster than
      single antidepressants.

PMID- 30278522
TI  - Effects of postoperative non-steroidal anti-inflammatory drugs on long-term
      survival and recurrence of patients with non-small cell lung cancer.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve
      postoperative fever, surgery pain, and inflammation. In addition, NSAIDs have
      anticancer activity and may reduce the risk and mortality of several cancers.
      However, the association between postoperative NSAIDs and the clinical outcome of
      non-small cell lung cancer (NSCLC) patients with fever after surgery is not fully
      understood. We performed a retrospective study of NSCLC patients who underwent
      surgery between July 2011 and June 2012, aiming to evaluate the effect of
      postoperative NSAIDs on overall survival (OS) and progression-free survival
      (PFS). Differences in clinical data between the postoperative NSAIDs group and
      non-NSAIDs groups were analyzed by Chi-square tests. Kaplan-Meier curves method
      and Cox regression analysis were conducted for survival analysis. The primary and
      secondary endpoints were OS and PFS, respectively. This retrospective study
      included 347 NSCLC patients. There were no significant differences in the
      clinical characteristics between the NSAIDs group and non-NSAIDs group except for
      age (P = .024) and differential degree (P = .040). Administration of
      postoperative NSAIDs was related to longer OS (hazards ratio [HR] 0.528, 95%
      confidence interval [CI] 0.278-0.884, P = .006) and longer PFS (HR 0.557, 95% CI
      0.317-0.841, P = .002) in the multivariate Cox regression model. Subgroup
      analysis showed statistically significant differences in elderly individuals,
      male subjects, low smoking index, poor differentiation, and non-adenocarcinoma
      subgroups, respectively. In conclusion, the administration of postoperative
      NSAIDs was related to longer OS and PFS in NSCLC patients with postoperative
      fever.

PMID- 30278523
TI  - Development and validation of the hypertensive intracerebral hemorrhage prognosis
      models.
AB  - To develop and validate the prognosis model of hypertensive intracerebral
      hemorrhage based on admission characteristics, which would be applied to predict
      the 3-month outcome.For developing the prognosis models, we studied data from 325
      patients with retrospectively consecutive hypertensive intracerebral hemorrhage
      admitted between 2012 and 2016. The predictive value of admission characteristics
      was tested in logistic regression models, presenting 3-month outcome as the
      primary outcome. The performance of the models was tested by discrimination and
      calibration. After development, internal and external validations were used to
      test the function.The multivariate analysis of logistic regression indicated that
      age, Glasgow coma scale score, pupillary light reflex, hypoxemia, intracerebral
      hemorrhage volume, blood glucose, and D-dimer level were independent factors of
      the hypertensive intracerebral hemorrhage prognosis model. The prognosis model
      based on those admission risk factors worked well. The receiver operating
      characteristic curve was used to analyze the discriminant ability of model A,
      model A + B, and model A + B + C. Specifically, the area under the receiver
      operating characteristic curve increased from 0.816 (model A; 95% CI, 0.760
      0.872) to 0.913 (model A + B + C; 95% CI, 0.881-0.946), and the models were not
      overoptimistic and were applicably confirmed by internal and external validations
      respectively.This prognosis model could be used to predict the prognosis of
      patients with hypertensive intracerebral hemorrhage early, simply and accurately,
      contributing to the clinical treatment eventually.

PMID- 30278524
TI  - Quantitative evaluation of myocardial layer-specific strain using two-dimensional
      speckle tracking echocardiography among young adults with essential hypertension
      in China.
AB  - The myocardial wall of the left ventricle is a complex, multilayered structure,
      which is altered in young adults with hypertension. The aim of this study was to
      define the characteristics of longitudinal and circumferential strain in young
      adults with hypertension.Two-dimensional speckle tracking echocardiography was
      used to analyze longitudinal and circumferential strain parameters in 67 young
      adults with hypertension, 70 older young adults with essential hypertension and
      62 healthy adults.The global longitudinal strain (GLS) and global circumferential
      strain (GCS) was the highest at endocardium, and lowest at epicardium. A layer
      specific analysis of myocardial deformation in all adults revealed that all of
      the peak systolic longitudinal strain (LS) and the peak systolic circumferential
      strain (CS) in the endocardium, mid-myocardium and epicardium were gradually
      increased from the base to the apex. The peak systolic LS showed significant
      differences at basal, mid-ventricular, and apical level among normal adults,
      young NLVH (nonleft ventricular hypertrophy), and young LVH (left ventricular
      hypertrophy). In all the adults with hypertension, young adults were associated
      with higher peak systolic longitudinal strain values compared with older adults,
      but the small differences of LS may be meaningless in clinical settings. Between
      the young LVH and older LVH, the peak systolic CS showed significant differences
      except data of epicardium at basal and mid-ventricular level.This study provides
      reference values for layer-specific strain in young adults with hypertension.
      This detailed strain analysis provides layer-oriented information to reveal the
      different characteristics of circumferential and longitudinal strain in young
      adults with hypertension. This systolic dysfunction could be detected
      conveniently and accurately by 2DSTE.

PMID- 30278525
TI  - Epigenetic differences of chronic hepatitis B in different TCM syndromes:
      Protocol for a case-control, non-interventional, observational clinical study.
AB  - INTRODUCTION: Chronic hepatitis B is a serious disease causing serious harm to
      the human health. Chinese medicine has its unique advantages in the clinical
      prevention and treatment, while the syndrome of Chinese medicine lacks the
      understanding at the micro level. There are some theoretical commonalities
      between the epigenetics and traditional Chinese medicine (TCM) syndromes. The
      biological basis of chronic hepatitis B (CHB) syndrome differentiation from the
      perspective of epigenetics is of great significance to diagnose and prevent the
      diseases. METHODS: This protocol is a case-control, noninterventional,
      observational clinical study. Patients with CHB for spleen-stomach damp heat and
      liver depression and spleen deficiency, with 12 each and 11 healthy volunteers
      were recruited. Peripheral venous blood was collected from the participants. DNA
      methylated transferase, genomic DNA methylated spectrum, methylated DNA binding
      protein MeCP2, chronic infection of hepatitis B virus with methylated related
      proteins, and miRNA target genes were analyzed. OBJECTIVES: From the perspective
      of DNA methylation epigenetics, "DNA methylation-miRNA-Target gene" is the main
      line, which further reveals the essence of TCM syndrome. To improve the level of
      TCM clinical syndrome differentiation and the clinical efficacy of TCM,
      especially in the study of TCM syndromes of CHB, discovering its underlying
      biological signature is necessary. TRIAL REGISTRATION: Clinical Trials
      Registration: ChiCTR1800017365, registered 26 July 2018.

PMID- 30278526
TI  - Treatment with normobaric or hyperbaric oxygen and its effect on
      neuropsychometric dysfunction after carbon monoxide poisoning: A systematic
      review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Carbon monoxide (CO) poisoning may result in acute neurological
      sequelae, cognitive sequelae, and delay neurological sequelae. The administration
      of hyperbaric oxygen (HBO) to prevent the development of delayed neurological
      sequelae in CO poisoning have extensively investigated but conflicting results
      have been reported. We performed a systematic literature review and meta-analysis
      of randomized controlled trials (RCTs) evaluating HBO treatment and its effect on
      neuropsychometric dysfunction after CO poisoning. METHODS: We searched Medline,
      Embase, Pubmed, and the Cochrane Register of Controlled Trials from inception to
      December 2017. Eligible studies compared HBO therapy with normobaric oxygen (NBO)
      in patients with CO poisoning. RESULTS: Six studies compared HBO with NBO in CO
      poisoning patients. Compared with patients treated with NBO, a lower percentage
      of patients treated with HBO reported headache (16.2% vs 16.5%, relative risk
      [RR] = 0.83, 95% CI = 0.38-1.80), memory impairment (18.2% vs 23.8%, RR = 0.80,
      95% CI = 0.43-1.49), difficulty concentrating (15.0% vs 18.4%, RR = 0.86, 95% CI
      = 0.55-1.34), and disturbed sleep (14.7% vs 16.2%, RR = 0.91, 95% CI = 0.59
      1.39). Two sessions of HBO treatment exhibited no advantage over one session.
      CONCLUSIONS: The meta-analysis indicated that compared with CO poisoning patients
      treated with NBO, HBO treated patients have a lower incidence of
      neuropsychological sequelae, including headache, memory impairment, difficulty
      concentrating, disturbed sleep, and delayed neurological sequelae. Taking into
      consideration the cost-effectiveness of one session of HBO, one session of HBO
      treatment could be an economical option for patients with CO poisoning with high
      severity.

PMID- 30278527
TI  - Immunohistochemical characterization of lymphangiogenesis-related biomarkers in
      primary and recurrent gliomas: A STROBE compliant article.
AB  - Glial tumors constitute the majority of primary intracranial brain tumors. The
      expression of specific markers of lymphangiogenesis in gliomas still remains
      unclear.A total of 40 surgical specimens from 20 patients with recurrent gliomas
      were included in the study. The expression of D2-40, vascular endothelial growth
      factor (VEGF)-C, VEGF-D, and VEGF receptor-3 (VEGR-3) was detected by
      immunohistochemistry (IHC). The clinicopathologic data (p53 and Ki67) were also
      collected and analyzed.At relapse malignant transformation rate was 65% (13/20
      cases). D2-40, VEGF-C, VEGF-D, and VEGFR-3 were expressed in 20%, 30%, 60%, and
      20% of primary and 45%, 30%, 75%, and 35% of recurrent glioma tumors (P < .01, P
      = 1.00, P = .03, P = .03). In 13 cases with increased malignancy grade, the
      expression of Ki67 and p53 were higher at relapse compared with the primary
      tumors (P = .001, P = .045). Multivariate survival analysis showed VEGF-D was an
      independent prognostic factor for malignant transformation (HR = 0.376, P =
      .045).Glioma is easy to relapse with tumor progression. VEGF-D was an independent
      prognostic factor for malignant transformation.

PMID- 30278528
TI  - Hyperthyroidism is not a significant risk of benign prostatic hyperplasia: A
      nationwide population-based study.
AB  - Benign prostatic hyperplasia (BPH) is a common disorder in the aging male
      population. Despite evidence that thyroid status impacts the prostate, the
      objective of this study was to examine whether patients with hyperthyroidism were
      at a greater risk for BPH.This study is a retrospective nationwide population
      based cohort study of the Chinese population. Data for this study were retrieved
      from the Taiwan National Health Insurance Research Database (NHIRD). Overall,
      1032 male patients aged 40 years or older with hyperthyroidism diagnosed between
      2000 and 2006 were included in the hyperthyroidism group, and 4128 matched
      controls without hyperthyroidism were included in the non-hyperthyroidism group.
      Both groups were monitored until the end of 2011. A Cox proportional hazards
      regression model was used to compute and compare the risk of BPH between study
      participants with and those without hyperthyroidism.Patients with hyperthyroidism
      exhibited a greater incidence of BPH (18.51% vs 15.53%) than did the controls.
      Furthermore, the hazard ratio (HR) of the hyperthyroidism group was 1.24 times
      that of the control group [95% confidence interval (95% CI 1.05-1.46)] signifying
      that there is a significant 24% increase in the risk of BPH with the presence of
      hyperthyroidism. This increased risk of BPH with hyperthyroidism, however, failed
      to remain significant (adjusted HR = 1.11, 95% CI = 0.94-1.3) after adjusting for
      covariates of age (adjusted HR = 2.72, 95% CI = 2.32-3.2), diabetes (adjusted HR
      = 1.4, 95% CI = 1.17-1.68), hypertension (adjusted HR = 1.74, 95% CI = 1.49
      2.03), hyperlipidemia (adjusted HR = 1.25, 95% CI = 1.03-1.53), neurogenic
      bladder, cystitis (adjusted HR = 1.23, 95% CI = 0.58-2.59), urethral stricture
      (adjusted HR = 2.01, 95% CI = 0.28-14.47), urethritis (adjusted HR = 1.52, 95% CI
      = 0.72-3.21), and urinary tract infection (adjusted HR = 1.77, 95% CI = 1.31
      2.39).After adjustment for comorbidities and covariates, hyperthyroidism was not
      found to be a significant risk factor of BPH in our male study subjects. Further
      research is warranted to validate our results and elucidate the association of
      the pathophysiology of these 2 diseases.

PMID- 30278529
TI  - Effects of the Chinese herb formula Yufeining on stable chronic obstructive
      pulmonary disease: A randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: A Chinese herb formula Yufeining (YFN) has showed promise in the
      treatment of stable chronic obstructive pulmonary disease (COPD), less is known
      that the impact of YFN in combination with standard Western treatments on lung
      inflammation. This study evaluated the safety and efficacy of YFN as a treatment
      for stable COPD and as an anti-inflammatory agent. METHODS: Sixty patients with
      stable COPD were randomly assigned to two treatment groups (YFN treatment, N =
      30; placebo treatment, N = 30). Both groups received inhaled steroids and
      bronchodilators during an 8-week intervention, and patient status was assessed at
      8 weeks later and 4 months after treatment. The primary outcome included clinical
      efficacy. The secondary outcomes involved CAT score, mMRC grade, six-minute
      walking distance (6MWD). IL-8, TNF-alpha, IL-17A, LTB4, TGF-beta1 and CRP were
      also detection in peripheral serum, as well as adverse reaction conditions.
      RESULTS: The YFN group demonstrated a significant improvement in clinical
      efficacy (compare 89.3% to 63.3% in the placebo group; P < 0.05). CAT scores and
      mMRC grades significantly decreased (P < 0.05, P < 0.01), and 6MWD significantly
      increased (P<0.05), after YFN treatment. The levels of IL-8, TNF-alpha, LTB4 and
      CRP decreased significantly after 8 weeks of treatment compared to baseline
      levels in both groups. Only in the YFN treatment group, the levels of IL-17A
      decreased significantly after treatment compared to baseline levels (P < 0.05).
      No changes were observed inTGF-beta1 from pre-to post-treatment in either group
      (P > 0.05). Serum levels of IL-8, TNF-alpha, IL-17A, LTB4 and CRP decreased
      significantly after YFN treatment compared to the placebo group (P < 0.05).
      CONCLUSION: A combinatorial treatment approach with YFN, inhaled steroids and
      bronchodilators produced a clinically effective treatment for stable COPD,
      leading to a significant decrease in circulating inflammatory mediators. The
      study appeared YFN was safety. CLINICAL TRIAL REGISTRATION NUMBER: No. ChiCTR-IOR
      17013577.

PMID- 30278530
TI  - Periocular triamcinolone acetonide injection for treating polypoidal choroidal
      vasculopathy concurrent with hemorrhagic retinal detachment.
AB  - To investigate the clinical efficiency of periocular triamcinolone acetonide (TA)
      injection for treating polypoidal choroidal vasculopathy (PCV) concurrent with
      hemorrhagic retinal detachment (HRD).Twenty-two cases confirmed with PCV
      concurrent with HRD characterized by massive subretinal hemorrhage and exudation
      presented to our department from January 2015 to May 2017 were included in this
      study. The initial vision varied from counting finger to 0.2. All cases were
      randomly divided into TA group (n = 12), which received periocular TA injection
      per month, and anti-VEGF group (n = 10), which were treated by anti-VEGF
      intravitreous injection per month. The patients were followed up for 6 months, in
      which fundus examination and visual acuity along with optical coherence
      tomography (OCT) were carried out.The treatment effect is divided into the
      following categories. Cure was defined as the elimination of subretinal
      hemorrhage and exudation accompanied by retinal edema and choroidal
      neovascularization (CNV) extinction and rise of visual acuity. Improvement was
      characterized by alleviation of subretinal hemorrhage and exudation accompanied
      by retinal edema and CNV reduction and rise of visual acuity. Ineffective means
      remained subretinal hemorrhage and exudation in fundus and no improvement of
      visual acuity, and polypoid lesions in OCT images. Among the 12 cases in TA
      group, 1 case was treated by periocular injection of TA twice, and 11 cases were
      treated by 3 times injection. After that, 3 cases (25%) were cured, 8 cases
      (66.7%) got improvement, and only 1 case (8.3%) showed no response. Although
      among 10 cases in the anti-VEGF group, 3 cases were treated by anti-VEGF
      intravitreous injection twice. Seven cases were treated by 3 times injection.
      After that, 4 cases (40%) got improvement, and the other 6 case (60%) showed no
      response. All patients showed no recurrence in the 6-month follow-up. No
      complications were noticed under periocular injection or intravitreous
      injection.Periocular TA injection is effective for treating PCV concurrent with
      HRD.

PMID- 30278531
TI  - The reasons and clinical treatments of postoperative relapse of Pott's disease.
AB  - Literature about postoperative relapse of Pott's disease is rare. Accordingly,
      the risk factors and clinical treatments for postoperative relapse of Pott's
      disease remain controversial. In order to evaluate the clinical outcomes of
      surgical treatment of postoperative Pott's disease relapse, and to investigate
      its optimal therapeutic procedures with respect to focal characteristics, we
      performed a retrospective review of clinical and radiographic data that were
      prospectively collected between July 2008 and May 2014 from 753 consecutive
      spinal tubercular patients including 67 patients who were diagnosed and treated
      as postoperative relapse of Pott's disease in our hospital. Apart from 9 patients
      being treated conservatively, the remaining 58 cases received surgery in our
      series. Specifically, 12 cases underwent anterior debridement, interbody fusion
      with instrumentation; 15 cases received posterior instrumentation anterior
      debridement, and bone grafting; 10 cases underwent posterior decompression, bone
      grafting, and instrumentation; 7 cases with debridement, 5 with debridement and
      sinus resection. Nine cases received percutaneous drainage and low-dose local
      continuous chemotherapy. Clinical outcomes before and after treatment were
      evaluated with statistical analysis based on hematologic and radiographic
      examinations, bone fusion, and neurologic status. Patients were followed-up for a
      mean of 39.2 +/- 8.2 months (range, 24-60 months). Postoperatively, the
      erythrocyte sedimentation rate (ESR) became normal within 4-6 months in all
      patients, and solid bone fusion was achieved within 8 months. Patients exhibited
      significant improvements in neurological deficits postoperatively, while the
      visual analog scale for pain showed significant improvements in all patients at
      final follow-up. The outcomes of follow-up showed that the reasons for
      postoperative relapse of Pott's disease were multiple. Individualized therapeutic
      methods should be chosen in accordance with the patient's general condition,
      recurrence focal characteristic, surgeon's experience, but above all is
      administration of appropriate chemotherapy.

PMID- 30278532
TI  - Tangier disease may cause early onset of atherosclerotic cerebral infarction: A
      case report.
AB  - RATIONALE: The present study explored the relationship between the adenosine
      triphosphate (ATP)-binding cassette A1 (ABCA1) gene, atherosclerosis, and
      cerebral infarction. The diagnosis and treatment ideas of stroke caused by
      Tangier disease via the summary of the diagnosis and treatment process of one
      case with juvenile stroke were explored. The relevant literature on the clinical
      manifestations, laboratory examinations, and treatment of Tangier disease was
      reviewed. PATIENT CONCERNS: The brain magnetic resonance imaging (MRI) of a
      juvenile man with acute onset of sudden right limb weakness and speechlessness
      revealed infarct lesions. The laboratory tests found low serum high-density
      lipoprotein (HDL), while further genetic testing identified ABCD1 gene mutation.
      The mother also carried the mutant gene. DIAGNOSES: Tangier disease was
      diagnosed. INTERVENTIONS: Statin treatment was administered for platelet
      aggregation. OUTCOMES: After 3 years of follow-up, the patient was declared to be
      in a stable condition. LESSONS: ABCA1 gene mutation caused early onset of
      atherosclerosis, leading to the occurrence of cerebral infarction. The cerebral
      infarction associated with reduced high-density lipoprotein (HDL), was under
      intensive focus with respect to ABCA1 gene. Child and Juvenile stroke patients
      with low HDL should not be excluded from the possibility of Tangier disease.

PMID- 30278533
TI  - Lumbar intraspinal microcystic/reticular schwannoma: Case report and literature
      review.
AB  - RATIONALE: Microcystic/reticular schwannoma (MRS) is a rare histological variant
      of schwannoma which was initially described in 2008 with a predilection for the
      visceral organs. This distinct tumor had been reported to mainly affect
      gastrointestinal tract, subcutaneous and soft tissue, various glands and head and
      neck region. However, MRS involving spine is extremely rare. PATIENT CONCERNS:
      The authors report the first case of MRS occurring in the lumbar (L) spinal canal
      of a 40-year-old male who presented with continuous pain and numbness in both
      feet for 2.5 years. Physical examination revealed weakness of lower extremities
      and hyperalgesia of both feet. DIAGNOSES AND INTERVENTIONS: The findings of pre
      operative investigation were suspicious for either a schwannoma or a spinal
      meningioma. Accordingly, total laminectomy, complete tumor resection,
      instrumentation and spinal fusion were performed. Post-operative histopathologic
      examination revealed a well-encapsulated neoplasm with reticular and microcystic
      growth pattern. Antoni A and Antoni B regions, Verocay bodies and hyalinized
      blood vessels were observed. And cytologic atypia, necrosis or mitosis was
      absent. Immunohistochemically, the tumor cells showed strong and diffuse
      positivity for S-100 as well as SOX 10. Therefore, a histopathological diagnosis
      of MRS was finally made. OUTCOMES: The patient remains well with no evidence of
      recurrence at a 22-month follow-up. LESSONS: This is the first case of MRS which
      is located in the L spinal canal. Awareness of this distinctive entity is helpful
      in preventing diagnostic pitfalls and making correct treatment strategies.

PMID- 30278534
TI  - Von Hippel-Lindau with early onset of hemangioblastoma and multiple drop
      metastases like spinal lesions: A case report.
AB  - RATIONALE: Hemangioblastoma is a rare tumor of the central nervous system (CNS).
      It is usually observed in patients with von-Hippel Lindau (VHL). The peak age for
      hemangioblastoma is between 20 and 50 years of age with very few cases over 65 or
      below 18 years of age. PATIENT CONCERNS: We report a female with a rare VHL
      mutation (c.337C>T) who was diagnosed with multifocal CNS hemangioblastoma at a
      very young age. DIAGNOSIS: At 17-years of age, she presented with obstructive
      hydrocephalus due to large cystic cerebellar mass. Imaging showed multiple
      lesions resembling drop metastases throughout her spinal cord.
      Immunohistochemistry of the resected tumor confirmed the pathological diagnosis
      of hemangioblastoma (World Health Organization Grade 1). INTERVENTIONS AND
      OUTCOME: She was treated with multi-stage resection of her primary and drop-
      metastasis like disease. She presented six months later with retinal
      hemangioblastoma while her other lesions were stable. She presented with multiple
      CNS and eye hemangioblastomas after failing to follow up for 2 years.
      Subsequently, Everolimus was started to treat her systemic disease. LESSONS: The
      unique feature of our case is the presence of multiple drop-metastases like
      spinal lesions, which has not been reported in the literature to be associated
      with hemangioblastoma.

PMID- 30278535
TI  - Recurrent cerebral microbleeds with acute stroke symptoms: A case report.
AB  - RATIONALE: Cerebral microbleeds are lesions that appear as round low signal
      intensity areas with a diameter of 2-5 mm on gradient echo T2-weighted sequence
      magnetic resonance imaging. Cerebral microblees are hemorrhages found in the
      brain parenchyma and they are caused by the extravasation of the blood. Although
      more patients with ischemic stroke are found to have cerebral microbleeds, only a
      few studies have evaluated other neurologic abnormalities outside of cognitive
      dysfunction due to cerebral microbleeds. PATIENT CONCERNS: A 73-year-old female
      patient had only a lacunar infarction with the development of a new microbleed
      whenever a new neurologic symptom occurred, without the occurrence of acute
      ischemic stroke. DIAGNOSES: A 73-year-old female patient diagnosed symptomatic
      cerebral microbleeds. INTERVENTIONS: Brain magnetic resonance imaging was taken
      within a few hours of the occurrence of a new symptom and we confirmed increased
      cerebral microbleeds in the ventral-posterolateral area of the thalamus,
      consistent with the symptoms. OUTCOMES: This case study is meaningful because it
      proves that repeated occurrences of cerebral microbleeds in a specific area can
      induce acute ischemic stroke-like symptoms. LESSONS: Cerebral microbleeds have
      been considered to be asymptomatic lesions thus far. However, recent studies have
      reported the association of cerebral microbleeds with neurological symptoms
      including cognitive dysfunction. This study confirmed the presence of newly
      formed cerebral microbleeds through imaging follow-ups whenever a symptom
      occurred.

PMID- 30278536
TI  - Change in lipid profile and risk of new-onset atrial fibrillation in patients
      with chronic heart failure: A 3-year follow-up observational study in a large
      Chinese hospital.
AB  - In chronic heart failure (CHF), new-onset atrial fibrillation (AF) is associated
      with increased morbidity and mortality. We aimed to evaluate the influence of
      dyslipidemia on the incidence of new-onset AF in patients with CHF.In this single
      center observational study, 308 patients with CHF and no history of AF were
      followed-up for 3 years. Of the 291 patients who attended the 1-year follow-up,
      78 had developed AF (AF group; 10 deaths), while 213 had not (sinus rhythm [SR]
      group). Changes in lipid profile (DeltaTC for total cholesterol and DeltaLDLc for
      low-density lipoprotein cholesterol) were analyzed.The groups differed
      significantly regarding the decrease in lipid levels from baseline to the 1-year
      follow-up (AF vs SR: for DeltaLDLc, 23.35 vs 7.80 mg/dL, P = .02; for DeltaTC,
      23.95 vs -2.76 mg/dL, P = .001). At the 3-year follow-up, new-onset AF was noted
      in 21 of the 188 living patients in the SR group. Cox proportional hazards
      analysis revealed DeltaLDLc and DeltaTC as independent risk factors for new-onset
      AF (hazard ratio, 1.018 and 1.013, respectively, per standard deviation
      increment), with higher incidence of new-onset AF for DeltaTC > 9.65 mg/dL (P =
      .02) and for DeltaLDLc > 9.73 mg/dL (P = .005).In CHF, pronounced decrease in
      LDLc and TC is associated with new-onset AF.

PMID- 30278537
TI  - Validation of a self-reported work disability questionnaire for ulcerative
      colitis.
AB  - Ulcerative colitis (UC) may severely limit patients' capacity to work. Recently,
      we validated a work disability questionnaire (WDQ) for Crohn disease. As UC
      shares clinical characteristics with Crohn disease, we hypothesized that the
      questionnaire might also be useful for UC. The study was aimed to validate the
      WDQ for use in UC.Consecutive patients with UC (n = 142, 67 women; age 48 +/- 1)
      completed the UC-WDQ and the inflammatory bowel disease questionnaire-9 (IBDQ-9),
      and EuroQoL-5D quality-of-life questionnaires. Validation of the UC-WDQ included
      an assessment of its construct validity, including: discriminant validity,
      convergent validity, and reproducibility (test-retest). We also calculated the
      intraclass correlation and the Cronbach alpha.The UC-WDQ is a valid and reliable
      tool for measuring work disability in patients with UC.

PMID- 30278539
TI  - Is Internet overuse associated with impaired empathic ability in Korean college
      students?
AB  - The purpose of the present study was to determine whether Internet overuse was
      associated with empathic ability in college students.A total 261 participants
      (145 males and 116 females; mean age of 21.93 years) completed Empathy Quotient
      (EQ), Young's Internet Addiction Test (IAT), and questionnaires about demographic
      data and internet using patterns.Of these 261 subjects, 85 (32.5%) were
      categorized as over-users. There was no significant difference in EQ total score
      between the over-user group and the average user group. The over-user group had
      lower scores of Social Skills than the average user group in subscale profiles.
      The over-user group stayed longer in cyberspace than the average user group. EQ
      score was found to have positive correlation with time spent in Internet use and
      the number of close friends.Results of the present study suggest that
      conventional Internet use is positively associated with empathic ability in
      interpersonal relationships. Therefore, such positive association between
      Internet use and empathic ability should be considered when evaluating possible
      problematic internet use.

PMID- 30278538
TI  - Relationship between short telomere length and stroke: A meta-analysis.
AB  - BACKGROUND: Several epidemiological studies had been carried out in different
      population cohorts to estimate the relationship between the shortened telomere
      length and stroke. However, the results still remained dispute. Consequently, we
      conducted this meta-analysis to estimate the relationship between them. METHODS:
      PubMed, EMBASE, and Web of Science were systematically searched for related
      articles to evaluate the association between "stroke" and "telomere length. STATA
      12.0 software was used to perform the meta-analysis. The Cochran Q test and
      inconsistency index (I) were used to assess the heterogeneity. Begg funnel plot
      and Egger test were used to assess publication bias. RESULTS: The meta-analysis
      was composed of 11 studies, consisting of 25,340 participants. We found a
      significant relationship between shortened telomere length and stroke (OR: 1.50,
      95% CI: 1.13-2.0; P = .005); however, in the prospective and retrospective study
      subgroup, we did not find a statistical significant relationship between
      shortened telomere length and stroke (the prospective subgroup: OR: 1.41, 95% CI:
      1-1.98; P = .051) (the retrospective subgroup: OR: 1.89, 95% CI: 0.96-3.72; P =
      .067).

PMID- 30278540
TI  - Lower circulating angiotensin II levels are related to the severity of
      preeclampsia and its risk as disclosed by a specific bioassay.
AB  - Preeclampsia is characterized by an increased sensitivity to angiotensin II (Ang
      II). We herein assessed whether serum Ang II levels measured by a new developed
      bioassay are associated with preeclampsia, its severity, and the risk for
      developing this disease.Using a cross-sectional design, we studied 90 pregnant
      women (30 healthy pregnant and 60 with preeclampsia [30 with- and 30 without
      severe features]). We also used a nested case-control study with 30 women who
      eventually developed preeclampsia and 31 normotensive controls. Serum samples
      were collected at diagnosis of preeclampsia or at 4-week intervals (from weeks
      12th to 36th). Ang II was measured using a bioassay.At diagnosis of preeclampsia,
      serum Ang II concentrations were significantly lower in preeclampsia without and
      with severe features (P = .001 and P < .001, respectively) than in healthy
      pregnancy. In addition, Ang II was different in preeclampsia with severe features
      than in those without severe features (P = .048). Women who subsequently
      developed preeclampsia had lower Ang II levels than women with normal
      pregnancies, and these changes became significant at 24 weeks onward. The risk to
      developing preeclampsia was higher among women with Ang II concentration values
      in the lowest quartile of the control distribution from 12 weeks onward (odds
      ratio ranging from 3.8 [95% CI 1.3-11.1] to 6.5 [95% CI 1.6-26.9]).We concluded
      that concentrations of Ang II are markedly diminished at diagnosis of
      preeclampsia and are closely associated with the severity of disease. Changes in
      circulating levels of Ang II precede the clinical presentation of preeclampsia.

PMID- 30278541
TI  - Repeated resection-associated breast angiosarcoma: A case report.
AB  - RATIONALE: As a very rare vascular tumor, breast angiosarcoma (AS) can be divided
      into primary and second breast AS. However, the latter is slightly more commonly
      detected in clinical practice. Radiation post mastectomy is the common cause for
      the secondary breast AS, and although there are other reasons, it is still quite
      rare. In the present study, we reported a rare case of breast AS and summarized
      the relevant literatures so that to conduce to diagnose AS. PATIENT CONCERNS: A
      50-year-old female with a history of right breast neoplasm was treated with
      repeat lumpectomy for 4 times during 8 years. DIAGNOSES: Mammogram and ultrasound
      examination demonstrated a possible malignancy (BIRADS-4B and BI-RADS-4C,
      respectively). Immunohistochemically positive for endothelial markers CD31, CD34,
      ERG, and FVIII-R-Ag. INTERVENTIONS: The patient underwent a right mastectomy with
      sentinel lymph node biopsy by our multidisciplinary team and no other therapy was
      given postsurgery. OUTCOMES: The patient had no recurrence after 3 months.
      LESSONS: Based on our findings, we concluded that repeated resection might be a
      risk factor for the breast AS, especially for a gradual pathological evolution
      from benign to malignant. This case showed a very rare cause for angiomatosis of
      breast, and the patient had a successful outcome after a simple mastectomy.

PMID- 30278542
TI  - Surgical management of retroperitoneal schwannoma complicated with severe
      hydronephrosis: A case report.
AB  - RATIONALE: Schwannomas are usually benign tumors arising from well-differentiated
      schwann cells, which rarely occur in the retroperitoneal space. The lack of
      specific signs and radiologic imaging characteristics makes preoperative
      diagnosis rather difficult. Most retroperitoneal schwannomas are benign and the
      primary treatment choice for retroperitoneal schwannomas is surgical excision,
      however, the involvement of the urinary system is scarcely reported. PATIENT
      CONCERNS: A 34-year-old woman presented with progressive left abdominal pain and
      rebound abdominal mass at the left lower quadrant for 1 month. Radiological
      imaging suggested capsulated solid mass with cystic and necrotic areas in the
      retroperitoneum accompanied by severe left kidney hydronephrosis and preoperative
      biopsy result was inconclusive. DIAGNOSES: We believe this is a rare case of
      retroperitoneal schwannoma complicated with severe hydronephrosis. INTERVENTIONS:
      After preparation, the patient underwent laparoscopy exploration and converted to
      open surgical exploration. The patient accepted complete surgical excision of the
      retroperitoneal tumor and left kidney. Postoperative pathology diagnosis of the
      mass was proven to be benign retroperitoneal schwannoma. OUTCOMES: Postoperative
      course of the patient was uneventful and the left abdominal pain was greatly
      improved. After 12-month follow up, no evidence of recurrence or any other
      complication including renal failure was observed. LESSONS: Preoperative imaging
      and preoperative ultrasound-guided biopsy are helpful to make accurate diagnosis.
      The final diagnosis is based on postoperative histological and
      immunohistochemical findings. The primary treatment option is complete surgical
      resection of the retroperitoneal schwannoma and the involved upper urinary system
      when severe hydronephrosis occured. Local recurrence and overall survival are
      closely correlated with negative resection margins and pathology types.

PMID- 30278543
TI  - Correlations of DAPT score and PRECISE-DAPT score with the extent of coronary
      stenosis in acute coronary syndrome.
AB  - Dual antiplatelet therapy (DAPT) score and PRECISE-DAPT score were recommended
      for decision making of optimal DAPT in discriminating the risk of thrombosis and
      bleeding. But the relationships between 2 scoring tools with the extent of
      coronary stenosis have not been established.We retrospectively enrolled 359
      patients of acute coronary syndrome (ACS) who received percutaneous coronary
      intervention. Both DAPT score and PRECISE-DAPT score were calculated, and
      patients were divided by their recommended cut-offs. Gensini score and triple
      vessel disease (3-VD) were chosen to evaluate the severity of coronary
      stenosis.Overall, 54.9% and 10.0% of the patients had higher DAPT score (>=2) or
      PRECISE-DAPT score (>=25). Patients with higher DAPT score had increased stent
      counts, total length of stents, Gensini score, and proportion of 3-VD, but
      decreased minimum diameter of stent. But these differences were not found in
      PRECISE-DAPT subgroups. When divided into quartiles of both scoring systems, the
      highest Gensini score and proportions of 3-VD were found in the fourth quartile
      of both DAPT score and PRECISE-DAPT score. Moreover, both DAPT score and PRECISE
      DAPT score were independent risk factors of Gensini score after adjustment (P <
      .001 and P = .047). Furthermore, an increase of 1 point of DAPT score and 5
      points of PRECISE-DAPT score resulted by 51% (odds ratios [OR]: 1.51, 95%
      confidence interval [CI]:1.19-1.91, P = .001) and 34% (OR: 1.34, 95% CI: 1.11
      1.62, P = .003) increase in risk of 3-VD after adjustment.Both DAPT score and
      PRECISE-DAPT score were independently associated with the degree of coronary
      stenosis in patients with ACS.

PMID- 30278544
TI  - Effect of preemptive dezocine before general anesthesia on postoperative
      analgesia in patients undergoing laparoscopic cholecystectomy: A prospective
      observational study.
AB  - Dezocine is proposed as an adjunctive analgesic for postoperative pain control.
      This randomized, double-blind, controlled study aimed to investigate the effect
      of preoperative Dezocine therapy on postoperative pain following laparoscopic
      cholecystectomy as well as the underlying mechanisms.Eighty patients scheduled
      for laparoscopic cholecystectomy were randomly allocated into 2 groups as
      follows: patients in Group D received Dezocine 0.15 mg/kg before anesthesia
      induction and patients in Group S received same volume of saline. The pain
      intensity, sedation score, sufentanil-based patient-controlled analgesia (PCA)
      consumption were recorded for 24 hours after surgery. Plasma concentrations of
      norepinephrine and serotonin were also measured.During the first 24 hours after
      surgery, the patients in Group D experienced lower pain score assessed by
      numerical rating scale (NRS) at 3 hours (rest: P = .038; movement: P = .036), 6
      hours (rest: P = .038; movement: P = .036), 12 hours (rest: P = .038; movement: P
      = .036), and 24 hours (rest: P = .038; movement: P = .036). Dezocine also
      decreased the sedation levels at 5 minutes (P = .031) after arrival at the PACU.
      Sufentanil-based PCA consumption in Group D was decreased when compared with
      Group S in the second to fourth phase after surgery (6-12 hours: P = .017; 12-18
      hours: P = .003; 18-24 hours: P = .039). Plasma norepinephrine and serotonin
      concentrations were higher in the Group D at 24 hours after surgery
      (norepinephrine: P = .009, serotonin: P = .042). In addition, Group D showed less
      incidence of nausea/vomiting (P = .032) as well as a higher postoperative
      satisfaction score after surgery (P = .017).In conclusion, preemptive Dezocine
      administration is suggested to be useful for the management of postoperative pain
      in short-lasting surgery such as laparoscopic cholecystectomy.

PMID- 30278545
TI  - Characteristics of overlooked synchronous gastric epithelial neoplasia after
      endoscopic submucosal dissection.
AB  - Since endoscopic submucosal dissection (ESD) has been accepted as the treatment
      of choice for early gastric cancer (EGC) without risk of lymph node metastasis,
      synchronous gastric epithelial neoplasia is no longer rare in the clinical
      practice. Knowledge about the characteristics associated with synchronous gastric
      epithelial neoplasia is of great importance to prevent delayed diagnosis.Between
      November 2008 and December 2014, a retrospective study was conducted in a single
      tertiary referral hospital. Consecutive patients who underwent ESD due to EGC or
      high-grade dysplasia were analyzed to evaluate the incidence of synchronous
      gastric epithelial neoplasia and the factors associated with synchronous and
      overlooked synchronous lesions.A total of 488 patients were analyzed in this
      study. Synchronous lesions were found in 59 patients (12.1%) during the mean 37.7
      months of follow-up. Among 77 synchronous lesions, 25 lesions (32.4%) were
      overlooked at the time of initial ESD. Age of >= 65 years, moderate to severe
      endoscopic atrophic gastritis, and elevated morphology of primary lesions were
      associated with synchronous gastric epithelial neoplasia. An important factor
      associated with overlooked lesions is the non-elevated morphology of
      lesions.Careful endoscopic examination of the whole stomach is necessary in
      patients who are older and who have moderate to severe atrophic gastritis and
      elevated morphology of lesions to prevent delayed diagnosis of synchronous
      gastric epithelial neoplasia, especially non-elevated lesions.

PMID- 30278546
TI  - Association between NR3C1 rs41423247 polymorphism and depression: A PRISMA
      compliant meta-analysis.
AB  - BACKGROUND: A dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is
      closely related to the occurrence of depression. The glucocorticoid receptor,
      also known as the nuclear receptor subfamily 3, group C, member 1 (NR3C1),
      provides negative feedback to the HPA axis by binding to glucocorticoids. Some
      studies have demonstrated an association between the NR3C1 rs41423247
      polymorphism and depression, but results from other studies have been
      controversial. METHOD: In this study, the association between the NR3C1
      rs41423247 polymorphism and depression was evaluated by a meta-analysis using the
      RevMan 5.3 software, and the Stata 10.0 software was used for sensitivity
      analysis and publication bias test. According to the inclusion criteria, related
      studies in databases were retrieved and screened. RESULTS: In total, 9 articles
      were selected, including 1630 depressed patients and 3362 controls. The meta
      analysis showed that homozygous mutation of NR3C1 rs41423247 was associated with
      depression in the total population (OR = 0.77, 95% CI = 0.64-0.94, P = .01) and
      in Caucasians (OR = 0.78, 95% CI = 0.63-0.96, P = .02). CONCLUSION: This meta
      analysis demonstrates that the NR3C1 rs41423247 homozygous mutation may be a risk
      factor for depression.

PMID- 30278547
TI  - Hemodynamic management of a patient with a huge right atrium myxoma during
      thoracic vertebral surgery: A case report.
AB  - RATIONALE: Myxoma is the most common primary benign cardiac tumor, which could
      lead to some fatal complications because of its strategic position. PATIENT
      CONCERNS: The patient was admitted to our hospital due to sudden onset of
      palpitation, chest tightness, mild fever, night sweats, accompanied with
      bilateral lower extremities adynamia, and paralysis for 5 days, but no obvious
      syncope and edema. DIAGNOSES: Transthoracic echocardiography showed a giant
      mobile myxoma (72 * 58 mm) in the right atrium (RA). Magnetic resonance imaging
      revealed an erosive space-occupying lesion located between the first and third
      thoracic vertebrae. INTERVENTIONS: Thoracic vertebral lesions were resected
      immediately to rescue the incomplete paraplegia. After the patient was placed in
      the prone position, significant hemodynamics changes were observed due to the
      displacement of the huge RA myxoma. OUTCOMES: Stable hemodynamics was maintained
      during the operation through control of fluid infusion combined with vasoactive
      drugs. LESSONS: Change in body position may lead to obstruction of intracardiac
      blood flow in patients with giant myxoma. This clinical manifestation is rarely
      reported.

PMID- 30278548
TI  - Tracheal diverticula: A retrospective analysis of patients referred for thoracic
      CT.
AB  - To assess the prevalence of tracheal diverticula (TD) in patients referred for
      thoracic Computed Tomography (CT).1679 consecutive patients subjected to thoracic
      CT examination for different causes, from January to June 2017, were included in
      this cohort study. CT was performed with a 64 slice CT, using a standard protocol
      and Multiplanar Reformat Images (MPR). A TD was defined as a thin-walled air sac
      at the paratracheal wall with a communication with the tracheal lumen. Congenital
      or acquired nature of TD was determined by the anatomical location, being usually
      the congenital ones located 4 to 5 cm below the vocal cords or a few centimeters
      above the carina in the right paratracheal area, whereas acquired ones were
      located at the level of the thoracic inlet, in the posterolateral tracheal wall.
      Presence of TD was assessed and their number and size recorded based on 2 axial
      diameters and size of neck.One or more TD were found in 96 patients (5.7% of
      sample), with a slight preponderance (65%) in male gender. Globally, 124 TD were
      detected; they were solitary in 75% of cases, double in 20.8%, and in about 4.2%
      they were triple. Average size of the TD was 1.3*4.9 mm with a mean width of the
      neck of 1.9 mm. The peak of prevalence (9%) was in patients belonging to the
      fourth-decade group (see ). According to their anatomical location, the majority
      (97.6%) of TD were acquired in nature and devoided of specific symptoms (see
      below).(Table is included in full-text article.)Acquired TD were detected in
      about 1 out of 20 of thoracic CTs and were usually incidentally. Our findings
      show a slightly higher frequency than previously reported. The most frequent
      presentation was in male and as a single entity. Clinically, TD was not
      associated with specific symptoms, in particular with chronic cough or Chronic
      Obstructive Pulmonary Disease (COPD).

PMID- 30278549
TI  - A rare myxoma-like right atrial thrombus causing syncope: A case report.
AB  - RATIONALE: Syncope is a complicated clinical condition involving various
      diseases. Syncope due to myxoma-like right atrial thrombus is rarely seen in
      patient without structural heart disease. PATIENT CONCERNS: A 61-year-old
      ambulant old male visited our emergency department for sudden syncope. DIAGNOSES:
      After the exclusion of neurological and coronary diseases, a right atrial block
      mass with a stalk connected to the atrial septum was accidentally found by
      echocardiography. Pulmonary embolism was subsequently revealed by computed
      tomographic pulmonary angiography. Atrial myxoma was initially suspected and
      surgical removal was conducted. Surprisingly, histological examination showed
      that the pedicled block mass was actually thrombus. INTERVENTIONS: The myxoma
      like right atrial thrombus and the emboli in the bilateral pulmonary trunks were
      resected. This patient received anticoagulant treatment with warfarin for 6
      months additionally. OUTCOMES: The patient was successfully discharged and being
      continually followed. CONCLUSION: This patient had a past medical history of
      right femoral neck fracture, which might be responsible for the formation of the
      myxoma-like right atrial thrombus. We should always consider echocardiography
      examination in syncope patient at risk of thrombus formation.

PMID- 30278551
TI  - Sarcomatous intrahepatic cholangiocarcinoma: Case report and literature review.
AB  - RATIONALE: Sarcomatous intrahepatic cholangiocarcinoma is a rare histological
      variant of cholangiocarcinoma (ICC). Previous medical literature has not
      mentioned the prevalence of this kind of disease, but a poorer prognosis than
      that of ordinary ICC was indicated. The diagnosis of the sarcomatous ICC is
      established on histopathological and immunohistochemical examinations. In this
      article, we present a new case of a patient with sarcomatous ICC who had no
      radiographic sign of intrahepatic tumor preoperatively. PATIENT CONCERNS: A 63
      year-old man was noted with cholecystolithiasis and right upper abdominal pain.
      Liver function was within normal limits, although the gamma-glutamyl
      transpeptidase level was elevated. Serum carbohydrate antigen 19-9 level was
      elevated. Radiography showed atrophy of the left lobe of the liver, high
      intensity signals on T1 weighted images, and low/high-intensity signals on T2
      weighted images in hepatic ducts. DIAGNOSES: The preoperative diagnoses were
      hepatolithiasis, choledocholithiasis, and cholecystolithiasis. INTERVENTIONS:
      Exploratory laparotomy, adhesion release, cholecystectomy, choledocholithotomy,
      and T tube drainage were performed. During the surgery, an ill-defined tumor was
      detected on the atrophic left lateral lobe of the liver. Hepatic left lateral
      lobectomy was performed to remove the mass. OUTCOMES: The final diagnosis of
      sarcomatous ICC was made by histopathology after surgery. No evidence of local
      recurrence or distant metastasis was noted on imaging during follow-up. LESSONS:
      Although rare, sarcomatous ICC does exist in patients presented with
      cholecystolithiasis and liver atrophy. Surgeons should be aware of the existence
      of sarcomatous ICC due to the poor prognosis. We recommend that multidisciplinary
      approaches may be key to improve prognosis, including adjuvant chemotherapy or
      radiotherapy.

PMID- 30278550
TI  - Pernicious anemia associated with cryptogenic cirrhosis: Two case reports and a
      literature review.
AB  - RATIONALE: Pernicious anemia (PA) is an autoimmune gastritis that results from
      the destruction of gastric parietal cells and the associated lack of an intrinsic
      factor to bind ingested vitamin B12. While an association between PA and various
      liver diseases has been rarely reported, reports of associated diseases include
      primary biliary cholangitis, autoimmune hepatitis, and Interferon-treated
      hepatitis C. We present 2 cases of PA associated with cryptogenic cirrhosis (CC),
      which has not been previously reported in the literature. PATIENT CONCERNS: A 42
      year-old man presented with fatigue, pallor, and sustained abdominal distension
      that had persisted for 15 days. An 87-year-old man was admitted to the hospital
      for an unsteady gait and loss of appetite that had persisted for 20 days.
      DIAGNOSES: Symptoms, laboratory tests, and imaging findings for both patients
      were indicative of PA and CC.Both had neurological and psychiatric symptoms
      during hospitalization that were ultimately linked to a vitamin B12 deficiency
      but not hepatic encephalopathy. INTERVENTIONS: Both patients received
      intramuscular injections of vitamin B12. OUTCOMES: Hemoglobin levels of the 2
      patients increased gradually, and their neurological symptoms were alleviated.
      LESSONS: PA associated with a liver disease is rare, and the underlying mechanism
      can only now be clarified. We speculate that autoimmune dysfunction and chronic
      vitamin B12 deficiency caused by PA might be unique causes of liver cirrhosis.
      Additional investigations are needed to verify these findings.

PMID- 30278552
TI  - Chronic kidney disease correlates with increased risk of pulmonary tuberculosis
      before initiating renal replacement therapy: A cohort study in Taiwan.
AB  - This study aimed to assess the association between chronic kidney disease (CKD)
      and the risk of pulmonary tuberculosis (TB) before initiating renal replacement
      therapy (RRT) in Taiwan.Total 16,052 subjects newly diagnosed with CKD between
      2000 and 2012 were included in the CKD group, and 31,949 randomly selected
      subjects who did not have CKD formed the non-CKD group. Subjects with a history
      of pulmonary TB or RRT, including dialysis and renal transplantation, before the
      index date were excluded. We determined the incidence of pulmonary TB at the end
      of 2013. A multivariable Cox proportional hazards regression model was used to
      assess the hazard ratio (HR) and 95% confidence interval (CI) for the risk of
      developing pulmonary TB associated with CKD.The overall incidence of pulmonary TB
      was 1.47-fold greater in the CKD group compared to that in the non-CKD group
      (4.94 vs 3.35 per 1000 person-years, 95% CI 1.39, 1.56). Multivariable Cox
      proportional hazards regression analysis showed that the adjusted HR of pulmonary
      TB was 1.45-fold higher in the CKD group (95% CI 1.27, 1.64) than in the non-CKD
      group. Male sex (adjusted HR 2.04), age (increase per one year, adjusted HR
      1.05), chronic obstructive pulmonary disease (adjusted HR 1.54), and diabetes
      mellitus (adjusted HR 1.34) were also associated with pulmonary TB.CKD is
      associated with an increased risk of developing pulmonary TB before the
      initiation of RRT.

PMID- 30278553
TI  - The elevated prevalence of risk factors for chronic liver disease among ageing
      people with hemophilia and implications for treatment.
AB  - Chronic liver disease (CLD) is frequently seen in the hemophilia population. The
      ADVANCE Working Group conducted a cross-sectional study in which people with
      hemophilia (PWH) aged >=40 years were included. This study aimed to assess the
      associations between CLD and its risk factors using data from the H3 study, and
      to suggest implications for optimal care.Data from 13 European countries were
      collected at a single time-point (2011-2013). Univariate and multivariate
      logistic regression (MLR) analyses were performed.A total of 532 PWH were
      included with either hemophilia A (n = 467) or hemophilia B (n = 65). A total of
      127 (24%) were diagnosed with CLD. Hepatitis C virus (HCV), human
      immunodeficiency virus (HIV), total cholesterol, and severe hemophilia were
      significant risk factors in univariate logistic regressions. In MLR, HCV Ab+/PCR+
      (OR = 17.6, P < .001), diabetes (OR = 3.0, P = .02), and HIV (OR = 1.9, P = .049)
      were positively associated with CLD. Total cholesterol (OR = 0.6, P = .002) was
      negatively associated with CLD. We found no evidence of interaction effects among
      the explanatory variables. No significant associations with age and type of or
      severity of hemophilia were observed in MLR.The main risk factors for CLD in this
      European cohort also apply to the general population, but the prevalence of HCV
      and HIV is considerably larger in this cohort. With new and improved treatment
      options, intensified eradication therapy for HCV seems justified to prevent CLD.
      Similarly, intensified monitoring and treatment of diabetes seem warranted.

PMID- 30278554
TI  - Effect of Tai Chi for post-stroke mental disorders and sleep disorders: A
      protocol for systematic review and meta-analysis.
AB  - BACKGROUND: Post-stroke mental disorders (PSMDs) and post-stroke sleep disorders
      (PSSDs) are very common in stroke patients. Recently, Tai Chi (TC) as a form of
      Chinese traditional mind-body exercise has been gradually applied to stroke
      rehabilitation although its efficacy for PSMD and PSSD varies across different
      studies. The aim of this study is to explore the therapeutic effect of TC
      training for PSMD and PSSD. METHODS: This review will only include randomized
      controlled trials (RCTs). Search strategy will be performed in 3 English
      databases, 4 Chinese databases, and the WHO International Clinical Trials
      Registry Platform. All English or Chinese RCTs, published from inception to
      February 28, 2019, will be sought. Two reviewers will screen, select studies,
      extract data, and assess quality independently. Primary outcomes are clinical
      scales, mainly including "Hamilton depression scale," "Hamilton anxiety scale,"
      and "Pittsburgh sleep quality index." The methodological quality including the
      risk of bias of the included studies will be evaluated using a modified
      assessment form, which is based on Cochrane assessment tool and Physiotherapy
      Evidence Database scale. Review Manager Software (Revman5.3) will be used for
      heterogeneity assessment, generating funnel-plots, data synthesis, subgroup
      analysis, and sensitivity analysis. We will use GRADE system to evaluate the
      quality of our evidence. RESULTS: We will provide some more practical and
      targeted results investigating the effect of TC exercise for PSMD and PSSD in the
      current meta-analysis. Meanwhile, we will ascertain study progress of TC for PSMD
      and PSSD and find out defects or inadequacies of previous studies, so that future
      researchers could get beneficial guidance for more rigorous study. CONCLUSION:
      The stronger evidence about TC's rehabilitative effect and safety for PSMD and
      PSSD will be provided for clinicians and policymakers. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42018106608. ETHICS AND DISSEMINATION: We do not apply
      for formal ethical approval from ethics committee because all of the study data
      in our review will be obtained in an anonymous way. Findings of this study are
      projected to be disseminated through peer-review publications.

PMID- 30278555
TI  - An interactive assistant for patients with cardiac implantable electronic
      devices: A study protocol of the LUCY trial.
AB  - Patients with chronic heart failure (CHF) and reduced left ventricle ejection
      fraction benefit from cardiac resynchronization therapy (CRT) and implantable
      cardioverter defibrillator (ICD). However, increasing numbers of patient with CRT
      and ICD devices produce overload of cardiology centers where patients are
      admitted to ambulatory visits. This study aims to find multivariate model
      predicting the requirement for ambulatory follow-up of cardiac implantable
      electronic devices (CIEDs).The LUCY study is an observational, cohort,
      prospective, 2-stage trial. As equal number of patients (300) will be included in
      the first and the second part of the study, finally, 600 patients will be
      included in the study. The inclusion criteria will be: age between 18 and 90
      years, CHF (New York Heart Association classes I-III) and implanted ICD or CRT at
      least 30 days before study inclusion. The exclusion criteria will be dementia and
      other conditions impeding cooperation during the study. All patients included in
      the study will undergo standard ambulatory visit. Primary endpoint will be
      defined as any ambulatory visit qualified as necessary due to patient's condition
      or device malfunction diagnose by the cardiologist: any change in pharmacotherapy
      related to patient's clinical status assessed during the visit, any change in
      tachyarrythmia counter or discriminator status, any change in tachyarrythmia
      threshold, presence of ventricular undersensing or oversensing, presence of
      atrial or ventricular ineffective pacing, or device's pocket infection. Secondary
      endpoint will be defined as any ambulatory visit qualified as necessary due to
      the alarm identified via Medtronic CareLink Express (MCLE): sustained or treated
      ventricular tachyarrythmia, any not previously diagnosed supraventricular
      tachyarrythmia, or elective replacement indicator.Our study is the first attempt
      of implementation of the machine learning and elements artificial intelligence in
      health care optimization of patients with CIED. The LUCY will be an open product,
      available for additional testing and improvement with supplementary
      functionalities: quality of life assessment, teleconsultation, video-streaming,
      automated imagine recognizing.

PMID- 30278558
TI  - Anterolateral approach for lateral humeral condylar fractures in children:
      Clinical results.
AB  - To evaluate the clinical outcomes of an anterolateral approach for lateral
      humeral condylar fractures in children. The patients aged < 15 years undergoing
      surgery with an anterolateral approach for humeral lateral condylar fractures
      between April 2005 and March 2014 were investigated. Medical records and
      radiographs from 15 patients were reviewed. Average patient age at surgery was
      6.0 years (range, 3-10 years). Based on Jakob's classification, 12 patients had
      type II fractures, and 3 patients had type III fractures. Based on Milch
      classification, 1 elbow was type I, and 14 elbows were type II. The average
      postoperative follow-up duration was 16.4 months (range, 6-58 months).
      Postoperative complications, and radiographic and clinical findings, including
      range of motion and Flynn criteria were evaluated. To evaluate humeral deformity,
      Baumann angle (BA) and the carrying angle (CA) were calculated on anteroposterior
      radiographs. There were no postoperative complications, including secondary
      displacement, deep infection, nonunion, avascular necrosis, or cubitus varus or
      valgus deformity. In the injured elbow, follow-up radiographs revealed an average
      BA of 69.1 degrees  (range, 57-84 degrees ), versus 70.9 degrees  (range, 61-83
      degrees ) on the contralateral side. The average CA on the injured side was 10.3
      degrees  (range, 4-20 degrees ) versus 12.3 degrees  (range, 6-24 degrees ) on
      the contralateral side. BA gain and CA loss (affected- compared with
      contralateral sides) averaged -1.4 degrees  (range, -17 degrees  to 9 degrees )
      and 2.3 degrees  (range, -2 degrees  to 6 degrees ), respectively. The mean range
      of motion in the affected elbow averaged 4.7 degrees  (range, 0-15 degrees ) in
      extension and 139.7 degrees  (range, 135-140 degrees ) in flexion. Over 5 degrees
      loss of range of motion in the affected elbow compared with the contralateral
      side was not observed. However, 2 patients experienced over 5 degrees  loss of CA
      in the affected elbow versus the contralateral side. Based on Flynn criteria,
      clinical results for both cosmetics and function were excellent in 13 patients,
      and good in 2. The advantages of the anterolateral approach are combining an
      optimal view of the anterior articular surface of the trochlea and capitellum and
      a limited risk of devascularization injury. We strongly recommend an
      anterolateral approach for these fractures in children to prevent postoperative
      deformity and to achieve anatomical reduction and reliable fixation.

PMID- 30278556
TI  - Comparison of periprosthetic bone remodeling after implantation of anatomic and
      tapered cementless femoral stems in total hip arthroplasty: A prospective cohort
      study protocol.
AB  - INTRODUCTION: Current total hip arthroplasty (THA) implant usage trends favor
      cementless fixation, and plenty studies have demonstrated that numbers of
      cementless femoral stems are associated with excellent long-term survivorship and
      functional outcomes. Various types of cementless femoral stems have been
      developed and utilized in multiple applications, including straight, tapered,
      anatomic, customized, short, and even neck stems. All of these designs aimed to
      achieve maximal primary stability and promote osseointegration. Nevertheless,
      stress-shielding and periprosthetic bone loss continue to occur and remain
      critical issues in promoting long-term survivorship of THA. Considering anatomic
      and tapered stems are the most popular cementless designs today, this prospective
      cohort study aimed to investigate the effect of stem design on stress-shielding
      and periprosthetic bone remodeling after implantation of an anatomic stem with
      proximal fixation (Ribbed Hip system; Waldemar Link, Hamburg, Germany) and the
      direct comparison to a fully coated tapered stem (LCU Hip system; Waldemar Link).
      MATERIALS AND METHODS: This prospective cohort study will comprise patients who
      receive primary unilateral THA with the Ribbed anatomic hydroxyapatite (HA)
      coated stem or LCU tapered fully HA-coated stem. The changes in periprosthetic
      bone mineral density after insertion of Ribbed and LCU stem prostheses will be
      assessed by means of dual-energy X-ray absorptiometry in the periprosthetic
      region of interest according to Gruen and colleagues. Standard anteroposterior
      and lateral plain radiography will be performed for qualitative assessment of the
      periprosthetic bone remodeling. The following items will be analyzed or measured
      on follow-up radiographs to compare with the initial appearance on the
      radiographs taken immediately postoperatively: cortical thickness in each Gruen
      zone, fitness of the distal stem within the isthmus, femoral stem alignment,
      radiolucent line, reactive line, periosteal bone reactions, and subsidence.
      Biologic fixation and stability of the cementless implant will be evaluated using
      Engh grading scale, and heterotopic ossification will be graded according to
      Brooker classification. Furthermore, Harris hip score and Western Ontario and
      McMaster Universities Osteoarthritis Index Score will also be assessed for
      postoperative functional evaluation. These radiologic and clinical assessments
      will be taken postoperatively, at 6 months, 1, 2, 3, 4, and 5 years after
      surgery. ETHICS AND DISSEMINATION: This study was approved by The First
      Affiliated Hospital of Chongqing Medical University Ethics Committee. The study
      results will be disseminated at national and international conferences and
      published in peer-reviewed journals. STUDY REGISTRATION: Chinese Clinical Trial
      Registry (http://www.chictr.org.cn): ChiCTR1800017841.

PMID- 30278557
TI  - Sonographic diagnosis of colorectal polyps in children: Diagnostic accuracy and
      multi-factor combination evaluation.
AB  - This study was established to evaluate the diagnostic value of ultrasonography in
      screening colorectal polyps in children and to discuss the necessity of colonic
      preparation before an ultrasonic examination.In this study, 288 children with
      colorectal polyps managed at our hospital between January 2007 and December 2016
      were retrospectively reviewed. All patients were examined before and after basic
      colon preparation. The colorectal polyps were confirmed by colonoscopy/laparotomy
      and histopathology. Among all 288 patients, solitary polyps were identified in
      278 patients (96.52%), and multiple polyps were identified in 10 patients (43
      polyps) (3.48%) by colonoscopy/laparotomy and histopathology.By ultrasonic
      examination, 264 cases (264/278) were detected as solitary polyp and 9 cases
      (9/10) as multiple polyps (31 polyps). In 278 solitary polyps, 180 (64.74%) were
      detected by ultrasonic examination without a colon preparation. Following
      glycerine enema (10-20 mL) treatment, 264 (94.96%) cases were detected by
      ultrasonic examination. The sensitivity and specificity of ultrasonography with
      glycerine enema for the detection of colorectal polyps were 94.96% and 100%,
      respectively. Colon preparation significantly increased the proportion of polyps
      identified by ultrasonography (P < .0001), as well as the diagnostic rate of
      polyps in rectum, sigmoid colon and descending colon (P < .05).Ultrasonography
      can be the primary diagnostic method for screening colorectal polyps in children
      on the strength of its safety, validity, and accuracy. Basic colon preparation
      with glycerine enema is recommended for children, which enable the detection of
      intraluminal lesions before ultrasonic examination.

PMID- 30278559
TI  - A broad ligament solitary fibrous tumor with Doege-Potter syndrome.
AB  - INTRODUCTION: Solitary fibrous tumors (SFTs) are uncommon mesenchymal neoplasms
      and are particularly rare in the female genital tract. Doege-Potter syndrome is a
      paraneoplastic syndrome involving SFT-associated hypoglycemia. We report, for the
      first time, on a broad ligament SFT with Doege-Potter syndrome; additionally, we
      review 30 cases of women with SFTs reported in the literature. PATIENT CONCERNS:
      A 37-year-old woman who presented with life-threatening hypoglycemia and a pelvic
      mass (16 * 15 * 15 cm). DIAGNOSES: The patient was diagnosed with broad ligament
      SFT with Doege-Potter syndrome. INTERVENTIONS: Tumor resection, sub-extensive
      hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy were
      performed, and 6 cycles of adjuvant chemotherapy were administered. OUTCOMES:
      Serum glucose levels returned to normal as soon as the tumor was resected. Forty
      3 months after operation, there was recurrence in the posterior peritoneal
      tissues. She underwent tumor resection and has remained tumor-free 28 months
      after this excision. CONCLUSION: Even though it is extremely rare, SFT should be
      quickly identified to prevent undue treatment delay and avoid unnecessary
      examination; surgery and long-term follow-up are recommended. SFT can be
      considered a highly invasive cancer, and intraoperative bleeding may occur.
      Although no correlation between adjuvant therapy and improved prognosis was
      found, further studies are required because of the small number of cases reported
      to date.

PMID- 30278560
TI  - Replacement of dexmedetomidine loading with midazolam for sedation in elderly
      patients with spinal anesthesia.
AB  - BACKGROUND: Dexmedetomidine is an effective sedative during spinal anesthesia.
      However, it requires a loading dose, which can result in transient hypertension,
      hypotension, bradycardia, and/or sinus arrest. In addition, the time required to
      reach an appropriate depth of sedation may cause anxiety to the patients.
      Therefore, we examined whether an intravenous bolus of midazolam could replace
      the loading dose of dexmedetomidine for sedation during surgery in elderly
      patients who received spinal anesthesia. METHODS: Patients aged over 60 years who
      scheduled to undergo total knee arthroplasty under spinal anesthesia were
      enrolled in this study. The patients were randomized into 2 groups. Patients in
      dexmedetomidine group (group D) (n = 20) were administered a loading dose of
      dexmedetomidine (1.0 MUg/kg over 10 min) intravenously followed by
      dexmedetomidine maintenance (0.5 MUg/kg/h). Patients in group MD (n = 20) were
      administered an intravenous midazolam (0.05 mg/kg) followed by dexmedetomidine
      maintenance (0.5 MUg/kg/h) intravenously. Heart rate (HR), mean arterial blood
      pressure (MBP), peripheral oxygen saturation (SpO2), and patient state index
      (PSI) were recorded. Ramsay sedation scale (RSS) scores were evaluated at 10
      minutes after drug administration and the end of surgery. RESULTS: A total of 40
      subjects were enrolled in the present study. At baseline, there was no between
      group difference in HR. Ten minutes after drug administration, group D had lower
      HR than group MD (62.1 +/- 9.4 versus 69.6 +/- 13.4, P = .047). PSI was
      significantly lower in group MD at 10 minutes after drug administration (82.8 +/-
      13.0 versus 72.0 +/- 16.0, P = .024); there was no between-group difference at 30
      and 60 minutes, and lower values in group D at the end of surgery (70.2 +/- 22.6
      versus 79.7 +/- 10.9, P = .011). The RSS score showed statistically significantly
      deeper sedation in group MD 10 minutes after drug administration, but no
      difference at the end of surgery. CONCLUSIONS: An intravenous bolus of midazolam
      is a viable alternative to dexmedetomidine loading for sedation during surgery in
      elderly patients who received spinal anesthesia. This is especially effective for
      patients who are at high risk for bradycardia or who want a faster sedation.

PMID- 30278561
TI  - Polymorphism of R353Q (rs6046) in factor VII and the risk of myocardial
      infarction: A systematic review and meta-analysis.
AB  - OBJECTIVE: Genetic components substantially contribute to the development of
      myocardial infarction (MI), and R353Q polymorphism (rs6046) in FVII gene has been
      suspected to be associated with the risk of MI. METHODS: A meta-analysis was
      conducted on the links between R353Q polymorphism and the susceptibility of MI. A
      comprehensive literature search was performed on 8 electronic databases. The main
      effects of the genotypes were estimated using a logistic regression approach. The
      odds ratios with 95% confidence intervals were calculated using the conventional
      summary method meta-analysis. The possible sources of heterogeneity among the
      included studies were explored using meta-regression analysis and subgroup
      analysis. RESULTS: A total of 18 eligible case-control studies, comprising of
      4701 cases and 5329 controls, were included. No overall statistical relationship
      was identified between R353Q and MI by any of the genetic models. The meta
      regression demonstrated that the Asian population, body mass index (BMI)
      category, and diabetes affected the heterogeneity. In addition, subgroup analyses
      showed that heterogeneities were identified in Asian population and BMI category,
      which highly agree with the results of meta-regression. CONCLUSIONS: The current
      meta-analysis suggested that R353Q polymorphism was not associated with the MI
      risk. Asian population, BMI category, and diabetes might be related to the
      incidence of MI. However, large-scale, case-control studies with rigorous designs
      are essential to provide accurate evidence.

PMID- 30278562
TI  - Importance of effusion of blood under the dura mater in forensic medicine: A
      STROBE - compliant retrospective study.
AB  - Subdural hemorrhage is commonly associated with mechanical brain injury and has a
      correspondingly high mortality rate. Subdural hematomas may immediately provoke
      symptoms or may be initially asymptomatic, with further symptoms evolving rapidly
      and fatally.The data regarding forensic autopsy of victims were obtained from The
      State Forensic Medicine Service of Lithuania between the years 2013 and 2016. A
      retrospective study was performed including 110 patients, whose cause of death
      was subdural hemorrhage. 95% confidence intervals were calculated.It was
      calculated, that in cases of sudden death, after subdural hemorrhage was
      diagnosed, a higher concentration of ethyl alcohol in blood (mean 2.22 +/- 1.3%)
      demanded a smaller amount of blood under the dura matter (mean 81.6 +/- 60.5 g)
      in order for the patient to die. It was also noted that hospitalized patients
      with subdural hemorrhage had a smaller concentration of blood ethyl alcohol (mean
      1.33 +/- 1%) and a larger amount of blood under the dura (mean 135.6 +/- 82.9
      g).Due to the toxic effect of ethyl alcohol, even a small amount (81.6 +/- 60.5
      g) of blood under the dura matter can determine a sudden death.

PMID- 30278563
TI  - Comparison of urine neutrophil gelatinase-associated lipocalin and interleukin-18
      in prediction of acute kidney injury in adults.
AB  - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18
      (IL-18) were considered as the most promising biomarkers in prediction of acute
      kidney injury (AKI), but the priority of them remains unclear. METHODS: Databases
      of PubMed, Elsevier, Cochrane library, and Web of science were searched until
      August 23, 2017 for studies investigated the diagnostic value of urine NGAL
      (uNGAL) and urine IL-18 (uIL-18) for AKI in adults. Statistical analysis and
      investigation of heterogeneity source were using RevMan5.3, MetaDiSc1.40, and
      Stata14.0. RESULTS: A total of 7 studies were included involving 2315 patients
      from 7 countries in this article, of whom 443 (19.1%) developed AKI. The present
      meta-analysis demonstrated that uNGAL was more valuable compare with uIL-18 with
      effect size of 1.09 (95% CI 1.03-1.15, P = .004) in specificity, but not in
      sensitivity with effect size of 1.12 (95% CI 0.98-1.29, P = .104). Subgroup
      analysis presented that research design may be a foundation affecting the
      diagnostic accuracy of uNGAL and uIL-18 for AKI. No substantial publication bias
      was found. CONCLUSIONS: uNGAL is more specific for prediction of AKI in adults as
      compared with uIL-18.

PMID- 30278564
TI  - Vonoprazan versus proton pump inhibitors for the management of gastroesophageal
      reflux disease: A protocol for a systematic review with meta-analysis.
AB  - BACKGROUND AND AIM: Vonoprazan, a novel potassium-competitive acid blocking
      agent, is used in the management of gastroesophageal reflux disease (GERD). We
      aim to perform a systematic review and meta-analysis for the comparison of the
      effects of vonoprazan and proton pump inhibitors (PPIs) in GERD in randomized
      controlled trials (RCTs). METHODS: A systematic and comprehensive search will be
      performed using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials
      (CENTRAL), Google Scholar, and clinical trial registries, for studies published
      up to September 2018. Only randomized clinical trials will be included. Primary
      outcomes of symptoms and esophageal erosion improvement in the intention-to-treat
      analysis, and secondary outcomes of symptoms and esophageal erosion improvement
      rate in the per protocol analysis, the comparative efficacy in terms of healing
      rate of esophageal erosion on endoscopy, the comparative efficacy in terms of
      improvement of esophageal impedance-pH study, adverse events, long-term safety,
      and the comparative efficacy in terms of CYP2C19 metabolite levels will be
      studied. The quality of included studies will be assessed using the modified risk
      of bias tool. Heterogeneity of estimates across studies as well as publication
      bias will be assessed. This systematic review and meta-analysis will be performed
      according to the protocol recommended by the Cochrane Collaboration and reported
      according to the preferred reporting items for systematic reviews and meta
      analysis (PRISMA) guidelines. All statistical analyses will be conducted using
      Stata SE version 15.0. RESULTS: The results of this systematic review and meta
      analysis will be published in a peer-reviewed journal. CONCLUSION: To our
      knowledge, this systematic review and meta-analysis will be the first to evaluate
      existing research comparing Vonoprazan and PPIs in GERD. Our study will provide
      information about the effect of vonoprazan and PPIs in GERD in RCTs. The review
      will benefit patients, healthcare providers, and policymakers.

PMID- 30278565
TI  - Knowledge of HIV status and antiretroviral therapy use among sexually transmitted
      infections service attendees and the case for improving the integration of
      services in South Africa: A cross sectional study.
AB  - We describe knowledge of human immunodeficiency virus (HIV) status, correct
      report of HIV status and antiretroviral therapy (ART) use among sexually
      transmitted infection (STI) service attendees in South Africa.An anonymous
      questionnaire was administered and serological HIV testing done. Proportions of
      attendees reporting knowledge of HIV status and HIV status consistent with
      laboratory results and ART use (among HIV positives) were determined as were
      factors associated with knowledge and inconsistent report of HIV status.Of 1054
      attendees, 288 (27.3%) were HIV positive and 830 (78.8%) self-reported knowledge
      of HIV status. Not knowing one's HIV status was associated with male gender
      [adjusted Odds Ratio (aOR) 2.66 (95% confidence interval (CI) 1.70-4.18] medical
      circumcision [aOR 0.48 (95% CI 0.24-0.95)] and site [Gauteng Province (GP)-aOR
      6.20 (95% CI 3.51-10.95), Eastern Cape (EC)-aOR 17.29 (95% CI 10.08- 29.66)
      versus Free State (FS)/Western Cape (WC) sites]. Of 219 HIV positive attendees
      with knowledge of HIV status, 136 (62.1%) self-reported being HIV positive, of
      whom 80 (58.8%) reported taking ARVs in the preceding 3 days. Inconsistent report
      of status was associated with males [aOR 2.26 (95%CI 1.05-4.87)], prior STI
      treatment [aOR 0.33 (95% CI 0.16-0.69)], recent HIV testing (6months) [aOR 3.20
      (95% CI 1.62-6.36)] and site [GP-aOR 6.89 (95% 3.21-14.82), EC-aOR 5.08 (95% CI
      2.15-11.64) versus FS/WC sites]. Knowledge of HIV status was lower than targeted.
      HIV testing and linkage to care services are essential in STI-related care and
      validation of self-reported indicators in this population maybe necessary.

PMID- 30278566
TI  - Effect of Montmorillonite powder on intestinal mucosal barrier in children with
      abdominal Henoch-Schonlein purpura: A randomized controlled study.
AB  - BACKGROUND: Our previous studies found that intestinal barrier function has been
      changed in children with abdominal Henoch-Schonlein purpura (HSP).
      Montmorillonite has been shown to be protective for digestive tract mucosa.
      OBJECTIVE: The present study aimed to investigate whether Montmorillonite powder
      could improve the intestinal mucosal barrier function in children with abdominal
      HSP. METHODS: Using a randomized controlled study design, we compared plasma
      levels of diamine oxidase (DAO), D-lactate, and endotoxin in children with
      abdominal HSP before and after Montmorillonite powder treatment. RESULTS: Among
      28 patients in experimental group and 30 in control group, there was no
      significant difference in age, sex, height, weight, and course of disease between
      2 groups (P > .05). Before treatment, there was no statistical difference in DAO,
      D-lactic acid, and endotoxin between experimental group and the control group (P
      > .05). However, significant differences were detected for DAO and D-lactate
      after treatment in comparison to before treatment in the Montmorillonite
      experimental group (P < .05). Such differences were not found in the control
      group (P > .05). CONCLUSION: Montmorillonite powder is effective in the treatment
      of HSP via maintaining intestinal mucosal barrier function.

PMID- 30278567
TI  - Apelin: A novel prognostic predictor for atrial fibrillation recurrence after
      pulmonary vein isolation.
AB  - Apelin, the ligand for the APJ receptor, is involved in the pathogenesis of
      atrial fibrillation (AF). However, whether serum apelin can predict the
      recurrence of AF after pulmonary vein isolation (PVI) has not been determined.A
      prospective cohort study was performed in patients with AF (but without
      structural heart disease) who were undergoing first-time PVI. Serum apelin-12 was
      measured by enzyme-linked immunosorbent assay. Echocardiographic examination was
      performed at baseline, 3 months, and 6 months after PVI. Patients were followed
      up for 6 months after PVI, and the association between baseline apelin-12 and AF
      recurrence (early recurrence: within 3 months after ablation; late recurrence: 3
      6 months after ablation) was analyzed.A total of 61 patients were included in the
      study. Baseline serum level of apelin-12 was significant lower in patients with
      early (median [interquartile range]: 1844 [1607-2061] vs 2197 [1895-2455] ng/L, P
      = .01) and late (1639 [1524-1853] vs 1923 [1741-2303] ng/L, P = .02) AF
      recurrence compared with patients without these events. Results of Cox stepwise
      multivariate analysis demonstrated that lower baseline apelin-12 (<2265 ng/L) was
      independently associated with increased AF recurrence within 6 months after PVI
      (P < .05). The specificity and positive predictive value of apelin-12 for AF
      recurrence were significantly higher than those of baseline N-terminal brain
      proBNP (60.4% vs 28.6%, P < .001; 58.8% vs 34.4%, P = .01), although the
      sensitivity and negative predictive value were similar.Reduced baseline serum
      apelin-12 may be an independent risk factor for the recurrence of AF after PVI in
      patients without structural heart disease.

PMID- 30278568
TI  - The use of 5% lidocaine medicated plaster for acute postoperative pain after
      gynecological surgery: A pilot randomized controlled feasibility trial.
AB  - OBJECTIVES: To examine the feasibility and potential efficacy of 5% lidocaine
      medicated plaster for acute postoperative pain in a parallel, blinded, randomized
      controlled pilot trial. METHODS: Twenty-eight women undergoing elective
      gynecological surgery with midline incisions were randomly allocated 5% lidocaine
      medicated patch (Lignopad) or placebo plasters. Postoperative pain at rest and on
      movement at 24 hours were the primary study endpoints, with secondary endpoints
      of postoperative pain within the first 48 hours, cumulative morphine consumption
      (mg), predicted peak flow rate (PFR) (%) and adverse effects. We assessed pain
      scores at rest and on movement using the visual analogue scale (0-100). RESULTS:
      The lidocaine patch group had lower postoperative pain scores at rest at 24 hours
      (mean difference [MD] -15.1, 95% confidence interval [95% CI] -28.3 to -2.0; P =
      .024) but not on movement at 24 hours (MD -6.4, 95% CI -22.7 to 9.9; P = .445).
      Compared to placebo, lidocaine may slightly lower cumulative morphine consumption
      (mg) over time (MD -3.4, 95% CI -6.9 to 0.2; group*time interaction P = .065).
      The difference in improvement in the PFR over time after surgery between groups
      appeared small (group*time P = .0980). No adverse effects occurred. CONCLUSIONS:
      Lidocaine patch may provide a clinically important reduction in postoperative
      pain intensity. A larger trial to confirm the efficacy and safety of lidocaine
      patch is feasible after modifying the inclusion criteria and collecting patient
      centered outcomes, such as quality of recovery and patient satisfaction.

PMID- 30278569
TI  - A double blind randomized placebo controlled pilot study of single-dose
      preoperative modafinil for functional recovery after general anesthesia in
      patients with obstructive sleep apnea.
AB  - BACKGROUND: We theorized that modafinil, an atypical psychomotor stimulant,
      utilized to improve daytime somnolence in patients with obstructive sleep apnea,
      would improve functional recovery after general anesthesia by improving time to
      extubation, post-anesthesia care unit (PACU) length of stay and subjective
      recovery after general anesthesia. METHODS: A double blind, randomized, placebo
      controlled pilot study was performed. 102 patients with the diagnosis of
      obstructive sleep apnea (OSA) were randomized to receive either 200 mg of
      modafinil or placebo before general anesthesia. The trial was terminated for
      futility. The primary outcome was PACU length of stay between groups. Secondary
      functional metrics of improved post-anesthesia recovery were compared between
      groups. RESULTS: No difference between groups was found on the primary outcome of
      PACU length of stay (PACULOS). Emergence from general anesthesia was not
      significantly different when assessed by the time period between termination of
      volatile anesthetic and extubation. Similarly, no difference between groups was
      found in intraoperative bispectral index (BIS) values, postoperative pain scores
      or narcotic consumption (morphine equivalent units). In the post-anesthesia care
      unit, respiratory rate was increased and mean arterial pressure was lower in the
      modafinil group. CONCLUSIONS: Our results suggest that the use of single-dose
      preoperative modafinil may not improve functional recovery after general
      anesthesia in patients with the diagnosis of OSA. Further research is needed
      before use of atypical psychomotor stimulants in this surgical population.

PMID- 30278570
TI  - Triglyceride to HDL-cholesterol ratio as an independent risk factor for the poor
      development of coronary collateral circulation in elderly patients with ST
      segment elevation myocardial infarction and acute total occlusion.
AB  - To determine the prognostic role of triglyceride (TG) to high-density lipoprotein
      cholesterol (HDL) ratio for poorly developed coronary collateral circulation
      (CCC) in elderly patients with ST-segment elevation myocardial infarction (STEMI)
      and acute total occlusion (ATO).As a retrospective case-control study, elderly
      patients (age >=60 years) with both STEMI and ATO (n = 346) were classified as
      having either poorly- or well-developed CCC (Rentrop grades 0-1 and 2-3,
      respectively). The ratio of TG/HDL was calculated according to the detected
      levels of TG and HDL. The difference of TG/HDL ratio in those 2 groups was
      compared by Student t test, and multivariate logistic regression analysis
      indicating occurrence of poorly developed CCC was performed. Receiver operator
      characteristic curve (ROC) analysis of TG/HDL ratio which determine the optimal
      cut-off value of TG/HDL ratio was applied.The TG/HDL ratio was significantly
      higher in patients with poorly developed CCC than in those with well-developed
      CCC (2.88 +/- 2.52 vs 1.81 +/- 1.18, P < .001). In multivariate logistic
      regression analysis, higher TG/HDL ratio (OR 1.789, 95% CI 1 . 346-2.378, P <
      .001) and the presence of left circumflex branch of coronary artery (LCX)
      occlusion (OR6.235, 95% CI 2.220-17.510, P = .001) were emerged as independent
      positive predictors of poor development of CCC, whereas presence of right
      coronary artery (RCA) occlusion (OR 0.474, 95% CI 0.265-0.850, P = .002) and
      onset time (OR 0.693, 95% CI 0.620-0.775, P < .001) were found as negative
      indicators. The optimal cut-off value of TG/HDL ratio was found as 1.58 in ROC
      analysis, which yielded an area under the curve value of 0.716 (95% CI 0.654
      0.778, P < .001) and demonstrated a sensitivity of 80.9% and a specificity of
      59.3% for prediction of poorly developed CCC.TG/HDL ratio is an independent risk
      factor for predicting poor development of CCC in elderly patients with STEMI and
      ATO.

PMID- 30278571
TI  - The role of third-line chemotherapy in recurrent or metastatic gastric cancer: A
      cohort study with propensity score matching analysis.
AB  - In recurrent or metastatic gastric cancer, second-line chemotherapy is generally
      recommended in current guidelines. Although third-line therapy is often performed
      in daily practice in some countries, there are only a few reports about its
      benefits.A retrospective review was conducted on 682 patients who underwent at
      least first-line chemotherapy for recurrent (n = 297) or primary metastatic (n =
      385) disease. Clinicopathological characteristics and overall survival (OS) were
      analyzed according to lines of chemotherapy.One hundred sixty-seven patients
      (24.5%) underwent third- or further-line therapy. Third- or further-line therapy
      was frequently performed in patients with young age (<70) (P < .0001), Eastern
      Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 (P < .0001),
      surgical resection before first-line therapy (P = .007), and first-line
      combination regimen (P = .001). The median OS for all patients after the
      initiation of first-line therapy was 10 months. The median OS of patients who
      received third- or further-line therapy was significantly longer than that of
      patients who received second- or lesser-line therapy (18 vs 8 months, P < .0001).
      The multivariate analysis revealed that third- or further-line therapy was
      independently associated with favorable OS (hazard ratio = 0.58, P < .0001).
      Moreover, patients who received third- or further-line therapy demonstrated
      better OS both in univariate (P = .002) and multivariate (P < .0001) analysis
      even after propensity score matching using baseline characteristics. The median
      OS after the start of third-line chemotherapy was 6 months. In addition, ECOG PS
      0 or 1 at the initiation of third-line therapy (P < .0001) and surgical resection
      (P = .009) were independently associated with longer OS after third-line
      therapy.The current study suggests that third-line therapy could be recommended
      for recurrent or metastatic gastric cancer patients with good PS after
      progression from second-line chemotherapy in clinical practice.

PMID- 30278572
TI  - Chinese herbal medicine for opioid induced constipation in cancer patients:
      Protocol for a systematic review.
AB  - BACKGROUND: Opioid induced constipation (OIC) is a symptom that is commonly
      encountered in cancer pain management. Chinese herbal medicine (CHM) has been
      widely used to improve OIC in China. Many clinical trials indicate that CHM could
      improve OIC. In this systematic review, we aim to evaluate the effectiveness and
      safety of CHM for OIC in cancer patients. METHODS: We will search the following
      electronic databases for randomized controlled trials to evaluate the
      effectiveness and safety of CHM for OIC in cancer patients: CENTRAL, EMBASE,
      MEDILINE, CINAHL and China National Knowledge Infrastructure. Each database will
      be searched from inception to June 2018. The entire process will include study
      selection, data extraction, risk of bias assessment and meta-analyses. RESULTS:
      This proposed study will evaluate the effectiveness and safety of CHM for OIC.
      The outcomes will include change in bowel movements, quality of life and adverse
      events. CONCLUSIONS: This proposed systematic review will evaluate the existing
      evidence on the effectiveness and safety of CHM for OIC in cancer patients.
      DISSEMINATION AND ETHICS: The results of this review will be disseminated through
      peer-reviewed publication. Because all of the data used in this systematic review
      and meta-analysis has been published, this review does not require ethical
      approval. Furthermore, all data will be analyzed anonymously during the review
      process.

PMID- 30278573
TI  - Clinical and cost-effectiveness of collaborative traditional Korean and Western
      medicine treatment for low back pain: A protocol for a prospective observational
      exploratory study.
AB  - BACKGROUND: In South Korea, a few patients with low back pain (LBP) are currently
      being treated with a combination of traditional Korean medicine (KM) and Western
      medicine (WM). Although a recent research has reported results regarding patient
      satisfaction and exploratory effectiveness, evidence of comparative effectiveness
      still needs to be reviewed. The aim of this study is to evaluate the clinical and
      cost-effectiveness of KM and WM collaborative treatment (CT) compared with that
      of sole treatment (ST) for patients with LBP in Korea. METHOD/DESIGN: This
      multisite, prospective observational comparative effectiveness research study is
      part of a nationwide pilot project for KM and WM collaboration launched by the
      Korean Ministry of Health and Welfare. The duration of the study is 8 weeks, and
      the target number of inclusion is 360 patients. Participants receive treatment
      according to their treatment plan, and a researcher conducts investigations
      thrice, every 4 weeks. In the final analysis, the merged data from the
      participants' questionnaire responses, hospital medical records, and
      administrative data, and Health Insurance Review and Assessment service data will
      be compared between the CT and ST groups. DISCUSSION: This study will provide
      clinical and economic information about CT for LBP, which might be a milestone
      for establishing future polices about this collaboration in Korea. TRIAL
      REGISTRATION: The study protocol has been registered with the Clinical Research
      Information Service (KCT0002827).

PMID- 30278574
TI  - Problems to affect long-term survival for breast cancer patients: An
      observational study of subsequent lung/bronchus malignancies.
AB  - The overall survival of breast cancer (BC) patients increased significantly for
      decades; however, their long-term survival was seriously impaired by subsequent
      malignancies. This study aimed to investigate the risk factors of subsequent lung
      / bronchus primary malignancies among BC survivors.A total of 535,941 BC female
      survivors diagnosed were identified by using SEERStat database in 1973 to 2014.
      Among them, 9398 had subsequent lung/bronchus malignancies. Clinico-pathological
      risk factors were evaluated for the development of subsequent lung/bronchus
      cancer. The main measures were the incidence and risk factors of subsequent
      lung/bronchus primaries. Logistic regression analysis and survival analysis were
      performed.Overall, among 535,941 BC survivors, 73,394 (13.69%) patients with
      subsequent primaries were identified from 1973 to 2014. The overall medium second
      tumor-free time was 72 months. Estrogen receptor (ER)-positive, progesterone
      receptor (PR)-positive, human epidermal growth factor receptor-2 (HER2)-positive,
      radiotherapy, and surgery treatment were protective factors against overall
      subsequent malignancies, whereas HER2/hormone receptor (HR) subtype triple
      negative, increasing tumor size, low differentiation grade, and high TNM stage
      were risk factors associated with overall subsequent malignancies. Surgical
      implantation reconstruction was risk factor for lung/bronchus cancer. Even though
      BC patients had a favorite 5-year survival, their long-term survival was affected
      by subsequent malignancies, especially for lung/bronchus cancer with high
      mortality.Nearly 13% BC survivors suffered from subsequent malignancies.
      Increased risk was related to HER2/HR triple negative and advanced TNM stages.
      Radiotherapy and surgery were protective factors. Our findings may inform the
      subsequent cancer counseling of female BC survivors.

PMID- 30278575
TI  - Associations of race, mechanism of injury, and neighborhood poverty with in
      hospital mortality from trauma: A population-based study in the Detroit
      metropolitan area.
AB  - Health disparities based on race and socioeconomic status are a serious problem
      in the US health care system, but disparities in outcomes related to traumatic
      injury have received relatively little attention in the research literature.This
      study uses data from the State Inpatient Database for Michigan including all
      trauma-related hospital admissions in the period from 2006 to 2014 in the Detroit
      metropolitan area (N = 407,553) to examine the relationship between race (White N
      = 232,109; African American N = 86,356, Hispanic N = 2709, Other N = 10,623),
      socioeconomic background, and in-hospital trauma mortality.Compared with other
      groups, there was a higher risk of mortality after trauma among African Americans
      (odds ratio [OR] = 1.20, P < .001), people living in high-poverty neighborhoods
      (OR = 1.01, P < .001), and those enrolled in public health insurance programs (OR
      = 1.53, P < .001). African American patients were more likely to have had
      traumatic injuries caused by certain mechanisms with higher risk of death (P <
      .001). After controlling for mechanism alone in multiple logistic regression,
      African American race remained a significant predictor of mortality risk (OR =
      1.12, P < .001). After additionally controlling for the socioeconomic factors of
      insurance status and neighborhood poverty levels, there were no longer any
      significant differences between racial groups in terms of mortality (OR = 0.99, P
      = .746).These results suggest that in this population the racial inequalities in
      mortality outcomes were fully mediated by differences between groups in the
      pattern of injuries suffered and differences in risk based on socioeconomic
      factors.

PMID- 30278576
TI  - Association between polycystic ovarian syndrome and endometrial, ovarian, and
      breast cancer: A population-based cohort study in Taiwan.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine disorder among the women
      of reproductive age. We conducted a nationwide population-based retrospective
      cohort study to analyze the association between PCOS and the subsequent
      development of gynecological cancers, namely endometrial, breast, and ovarian
      cancer.For this population-based cohort study, we used the Taiwan National Health
      Insurance Research Database, which contains information on approximately 24.7
      million insured individuals. The cohort included women who had received a
      diagnosis of PCOS between 1998 and 2013. An age-matched systematic random
      sampling method with a ratio of 1:4 was used for patient selection for the non
      PCOS reference cohort. Multivariate Cox proportional hazard regression analysis
      was used to determine the effects of PCOS on the risks of gynecologic and breast
      cancer. The data are presented as hazard ratios (HRs) with 95% confidence
      intervals (CIs).The PCOS cohort consisted of 8155 patients with PCOS, and the
      comparison cohort consisted of 32,620 matched patients without PCOS. The
      incidence of endometrial cancer was 226 and 15 per 100,000 person-years in the
      PCOS and comparison groups, respectively. A statistically significant higher risk
      of endometrial cancer was found in the PCOS cohort (adjusted HR [aHR] = 17.7, 95%
      CI = 4.9-64.2) than in the comparison cohort. However, no association was
      observed between PCOS and ovarian (aHR = 1.64, 95% CI: 0.63-4.27) or breast
      cancer (aHR = 0.98, 95% CI: 0.58-1.65).The results of this large population-based
      cohort study supported the premise that women with PCOS might have an increased
      risk of endometrial cancer, but no association between PCOS and the risks of
      ovarian and breast cancer was found.

PMID- 30278577
TI  - Can ultrasound be an assessment tool for sagittal spine mobility and chest
      expansion in patients with ankylosing spondylitis?
AB  - We aimed to examine whether ultrasound (US) is useful for evaluating spinal
      mobility and chest expansion in ankylosing spondylitis (AS) patients and
      determine a cutoff value to identify reduced sagittal lumbar mobility.Our cross
      sectional study included 50 AS patients and 50 controls. Metric measurements and
      Bath AS indices were measured in AS patients. The distance between C6-C7, T11
      T12, and L4-L5 vertebrae was measured, and the difference and percentage of
      difference between erect position and maximal cervical and lumbar flexion was
      calculated (T11-T12dif, T11-T12%, L4-L5dif, L4-L5%, T+L dif, T+L%). Intercostal
      divergence was measured 1.5 cm away on the left from the sternocostal space
      during maximum inhalation and maximum exhalation, and the difference and
      percentage of difference between them was calculated (ICdif, IC%).All metric
      measurements were lower in the AS group except for tragus-to-wall distance. T11
      T12dif, T11-T12%, L4-L5dif, T+L dif, and T+L% values were higher in the control
      group, while other US measurements did not differ between the groups. All US
      measurements except ICdif and IC% correlated with the Bath AS Metrology
      Index.Thus, US may be used for assessing spinal mobility in patients with AS. T11
      T12dif <0.79 cm may show decreased lumbar sagittal mobility.

PMID- 30278578
TI  - The clinical application value of the plasma copeptin level in the assessment of
      heart failure with reduced left ventricular ejection fraction: A cross-sectional
      study.
AB  - This study aimed to evaluate the clinical applicability of the plasma copeptin
      level to assess heart failure with reduced left ventricular ejection fraction
      (HFrEF).One hundred thirty-one patients with HFrEF, 127 patients with heart
      failure with preserved left ventricular ejection fraction (HFpEF), and 119
      healthy candidates were involved. The basic data and examination results of
      patients were collected. The heart function of the patients with HFrEF and HFpEF
      were graded on the basis of the criteria of New York Heart Association (NYHA)
      classification. The plasma copeptin and N-terminal pro-B-type natriuretic peptide
      (NT-proBNP) levels were tested using enzyme-linked immunosorbent assays
      (ELISAs).The copeptin and NT-proBNP levels were higher in the HFrEF group than in
      the HFpEF group. The copeptin and NT-proBNP values increased as the NYHA grade
      increased in the patients with HFrEF. However, for the patients with HFpEF, the
      copeptin levels did not change markedly as the NYHA grade increased. The copeptin
      levels were positively correlated with the NT-proBNP levels in the patients with
      HFrEF; however, there was no correlation between the copeptin and NT-proBNP
      values in the patients with HFpEF.Copeptin is involved in the process of
      progression in patients with HFrEF and the copeptin values might be useful for
      HFrEF prediction and assessment in the clinic.

PMID- 30278579
TI  - Raman characterizations of red blood cells with beta-thalassemia using laser
      tweezers Raman spectroscopy.
AB  - This study aimed to study the differences in Raman spectra of red blood cells
      (RBCs) among patients with beta-thalassemia and controls using laser tweezers
      Raman spectroscopy (LTRS) system.A total of 33 patients with beta-thalassemia
      major, 49 with beta-thalassemia minor, and 65 controls were studied. Raman
      spectra of RBCs for each sample were recorded. Principal component analysis
      (PCA), one-way analysis of variance (ANOVA), and independent-sample t test were
      performed.The intensities of Raman spectra of beta-thalassemia (major and minor)
      RBCs were lower than those of controls, especially at bands 1546, 1603, and 1619
      cm. The intensity ratio of band 1546 cm to band 1448 cm demonstrated that there
      was a significant difference between the spectra of beta-thalassemia major
      (mostly below 2.15) and those of controls. The spectra of controls could be well
      distinguished from those of beta-thalassemia major using PCA. After
      normalization, the spectra of two different genotypes with beta/beta mutations
      mainly overlapped, while those with beta/beta mutations had lower intensity at
      bands 1546, 1603, and 1619 cm.The present study provided Raman characteristics of
      RBCs in patients with beta-thalassemia major and supported the use of LTRS as a
      method for screening beta-thalassemia major. The recognition rate for beta
      thalassemia minor needs to be further improved.

PMID- 30278580
TI  - Coinfection with cryptococcus and aspergillus in an immunocompetent adult: A case
      report.
AB  - RATIONALE: Aspergillus and Cryptococcus exposure can cause serious secondary
      infections in human lungs, especially in immunocompromised patients or in
      conjunction with a chronic disease caused by low disease resistance. Primary
      invasive fungal infections are clinically rare; therefore, coexistence of 2 fungi
      at an infection site is uncommon. This paper reports a case of healthy male who
      was diagnosed with both Cryptococcus neoformans and Aspergillus infections.
      PATIENT CONCERNS: A healthy 33-year-old male office worker was admitted to the
      Second Hospital of Jilin University for hemoptysis. A chest computed tomography
      (CT) scan showed a cavity, which was formed by the thick dorsal wall of the lower
      left lobe with an irregular inner wall and burr changes around the lesion.
      INTERVENTION: After 1.0 week of antibiotic and antituberculosis treatment, the
      hemoptysis symptoms remained. A resection of the left lower lobe was performed.
      DIAGNOSES: The postoperative pathological reports indicated the presence of both
      Aspergillus and Cryptococcus. The 2 fungal lesions were separate but within the
      same location. OUTCOMES: After treatment, the patient no longer had hemoptysis.
      LESSONS: The current study indicated that fungi can infect not only
      immunocompromised patients but also healthy people, and that there can be 2
      separate fungal infections at the same infection site.

PMID- 30278581
TI  - Alveolar architectures preserved in cancer tissues may be potential pitfalls for
      diagnosis and histological subtyping of lung cancer: Three case reports.
AB  - RATIONALE: Lung cancer is a leading cause of cancer-related deaths globally.
      Appropriate histopathological diagnosis and subtyping form the basis and are
      critical for clinical therapies. PATIENT CONCERNS: Here, we report about 3
      patients who had a nodule in the lung. Cancer cells grow in the alveolar cavity
      in many lung carcinomas. In all our 3 cases preserved alveolar architectures were
      found in tumor tissues which may lead to diagnostic pitfalls. DIAGNOSES: Three
      patients had tumors that were diagnosed as nonsmall cell lung cancers, including
      large-cell carcinoma, peripheral squamous cell carcinoma, and large-cell
      neuroendocrine carcinoma, all of which contained structures of preserved alveolar
      cells that could be mistaken as malignant glandular components. The preserved
      alveolar cells formed acinar or duct-like structures enwrapped in the lung cancer
      tissues or surrounded the nests of cancer cells. Proliferative alveolar cells
      adjacent to cancer tissues were observed, and papillary structures and marked
      atypia, both of which may be mistaken as part of adenocarcinoma or carcinoma with
      glandular differentiation, were also observed. INTERVENTIONS: All patients
      underwent surgery and postoperative chemotherapy. OUTCOMES: The patients had no
      recurrence at 5-, 8-, or 10-month follow-up after the last surgery. LESSONS:
      Preserved alveolar cells with different architectures may be observed in various
      lung cancer tissues and may be mistaken as adenocarcinoma or carcinoma with
      glandular differentiation. Distinct morphological and immunohistochemical
      features may help distinguish preserved alveolar cells from tumor components.

PMID- 30278582
TI  - Effects of neurofeedback versus methylphenidate for the treatment of attention
      deficit/hyperactivity disorder protocol for a systematic review and meta-analysis
      of head-to-head trials.
AB  - INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is developmental
      disorder characterized by inattention and/or hyperactivity/impulsivity.
      Psychostimulants, including methylphenidate (MPH), are recommended as a first
      line pharmacological intervention, whereas neurofeedback (NF) has been proposed
      as a nonpharmacological option. The comparative effects of MPH and NF need
      further exploration. We will conduct a systematic review and meta-analysis of
      head-to-head randomized controlled trials (RCTs) comparing the efficacy and/or
      tolerability of MPH and NF in children/adolescents and adults with ADHD. METHOD
      AND ANALYSIS: We will include published as well as unpublished data. Two
      investigators will independently search PubMed, OVID, ERIC, Web of Science,
      ClinialTrials.gov, and a set of Chinese databases, including CNKI, CQVIP, and
      WanFang for head-to-head RCTs comparing MPH and NF. Experts will be contacted for
      unpublished data. The primary outcome will be the efficacy on ADHD core symptoms,
      measured by the change in the severity of ADHD symptoms, from baseline to
      endpoint and, if available, at follow-up (at any available time point). Secondary
      outcomes will be: dropouts for any reasons; efficacy on neuropsychological
      measures (working memory, inattention, and inhibition). We will conduct subgroup
      analyses to assess the impact of the following variables: age; type of NF;
      language of publication; comorbidities. Additionally, we will carry out meta
      regression analyses to investigate the effect of sponsorship, year of
      publication, duration of intervention, and age of participants. Sensitivity
      analyses will be conducted to test the robustness of the findings. Risk of bias
      of individual studies will be assessed using the Cochrane risk of bias tool.
      Analyses will be performed using Comprehensive Meta-Analysis Software. ETHICS AND
      DISSEMINATION: No ethical issues are foreseen. Results from this study will be
      published in a peer-reviewed journal and presented at relevant national and
      international conferences. TRIALS REGISTRATION NUMBER: PROSPERO CRD42018090256.

PMID- 30278584
TI  - Awareness, incidence and clinical significance of acute kidney injury after non
      general anesthesia: A retrospective cohort study: Erratum.

PMID- 30278583
TI  - Increased EXT1 gene copy number correlates with increased mRNA level predicts
      short disease-free survival in hepatocellular carcinoma without vascular
      invasion.
AB  - Exostosin-1 (EXT1) has been demonstrated to participate in the progression of
      many cancers. However, it has not been previously described in patients with
      hepatocellular carcinoma (HCC) without vascular invasion. In this study, we got
      the accurate data of EXT1 mRNA Z-score from the CBio data portal of The Cancer
      Genome Atlas (TCGA), which was used to express the level of EXT1 gene expression.
      We analyzed the EXT1 gene expression between HCC and normal liver tissue and
      compared the clinical significance of tumor tissue's EXT1 gene expression of HCC
      patients without vascular invasion based on data from TCGA database. The
      association between EXT1 gene expression and disease-free survival (DFS) was
      further analyzed. EXT1 gene copy number was also analyzed in this study.
      Univariate and multivariate analyses showed that high EXT1 gene expression group
      was significantly poorer than that of the low EXT1 gene expression group (P =
      .004). In addition, EXT1 gene expression was positively associated with alpha
      fetoprotein (AFP), which is a well-known marker for HCC. There was a significant
      positive correlation between EXT1 copy number and upregulated EXT1 gene (P <
      .0001). In conclusion, upregulation of EXT1 could be an important indicator to
      the short DFS of HCC patients without vascular invasion. EXT1 gene copy number
      amplification is one of the mechanisms underlying the upregulation of EXT1.

PMID- 30278585
TI  - Identification of key microRNAs and their targets in exosomes of pancreatic
      cancer using bioinformatics analysis.
AB  - Pancreatic cancer (PC) is one of the most lethal tumors, due to late diagnosis
      and limited surgical strategies. It has been reported that serum exosomal
      microRNAs (S-Exo-miRNAs) play a pivotal role as signaling molecules and serve as
      noninvasive diagnosis methods for PC. The combination of S-Exo-miRNAs with the
      corresponding target also plays an important role in the tumor
      microenvironment.Here we investigated S-Exo-miRNAs involved in PC. The gene
      expression profile was downloaded from the Gene Expression Omnibus (GEO)
      database. The analysis was carried out using GEO2R. The targets of differentially
      expressed serum exosomal miRNAs (DE-S-Exo-miRNAs) were predicted by 4
      bioinformatic algorithms (miRanda, miRDB, miRWalk, and Targetscan). Further
      analysis with gene ontology (GO) and Kyoto Encyclopedia of Genomes pathway (KEGG)
      enrichment analyses were performed with Cytoscape software version 3.4.0.
      Subsequently, the interaction regulatory network of target genes was performed
      with the Search Tool for the Retrieval of Interacting Genes (STRING) database
      (http://www.string-db.org/) and visualized using Cytoscape software.We downloaded
      the gene expression profile GSE50632, which was based on an Agilent microarray
      GPL17660 platform containing 4 eligible samples. In total 467 DE-S-Exo-miRNAs
      were obtained, including 7 overexpressed miRNAs (1.50%), and 460 remaining
      underexpressed miRNAs (98.50%). The databases miRWalk, miRDB, miRanda, and
      TargetScan were used to predict their potential targets, which were subsequently
      submitted to Cytoscape software version 3.4.0 (www.cytoscape.org). Next the
      functional and pathway enrichment analysis were used for the KEGG pathway and GO
      categories analysis. The enrichment analysis identified the genes involved in
      such processes as developmental and negative regulation of multicellular
      organismal processes, regulation of anatomical structure morphogenesis,
      regulation of cell death, apoptotic processes and mitogen-activated protein
      kinase (MAPK) signaling pathway, transforming growth factor - beta (TGF -beta)
      signaling pathway, cyclic adenosine monophosphate (cAMP) signaling pathway, and
      the phosphatidylinositol-3 kinases/Akt (PI3K-Akt) signaling pathway. Subsequently
      according to the protein-protein interaction (PPI) network, the top 10 genes were
      obtained. The enrichment analyses of the genes involved in a significant module
      revealed that these genes were related to the TGF-beta signaling pathway. After
      reviewing the literature, we identified the apoptosis genes, and their
      corresponding miRNAs that have a relationship with apoptosis of the tumor.This
      analysis provides a comprehensive understanding of the roles of S-Exo-miRNAs and
      the related targets in the development of PC. Additionally, the present study
      provides promising candidate targets for early diagnosis and therapeutic
      intervention. However, these predictions require further experimental validation
      in future studies.

PMID- 30278586
TI  - Prognostic factors to survival of patients with chondroblastic osteosarcoma.
AB  - This study was aimed to reveal the changes in survival rates and prognostic
      factors to survival of chondroblastic osteosarcoma (COS).Patients from the
      Surveillance, Epidemiology, and End Results (SEER) database were retrieved.
      Kaplan-Meier survival analysis and Cox proportional hazard model were used during
      analysis.There were significant differences on overall survival between subtypes
      of osteosarcoma (P < .001*). Overall survival of COS did not change significantly
      during last forty years (P = .610), and cancer-specific survival increased to a
      plateau in 1980s and then remained stable (P = .058). Younger onset age, patients
      of white race, well and moderately differentiated tumors, and surgery
      independently predicted better overall (Hazard ratio [HR]: 1.034, P < .001*; HR:
      0.538, P = .004*; HR: 0.240, P = .020* and HR: 0.350, P < .001*, respectively)
      and cancer-specific (HR: 1.031, P = .002*; HR: 0.592, P = .036*; HR: 0.098, P =
      .027* and HR: 0.253, P < .001*, respectively) survival. Metastasis at diagnosis
      independently predicted worse overall (HR: 3.108, P < .001*) and cancer-specific
      (HR: 4.26, P < .001*) survival compared to no metastasis.Younger onset age, white
      race, well and moderately differentiated tumors, no metastasis at diagnosis and
      surgical resection can independently predict better overall and cancer-specific
      survival of COS.

PMID- 30278587
TI  - Repeated cardiac arrest caused by an air embolism during hepatic resection: A
      case report.
AB  - RATIONALE: Although venous air embolism (VAE) during liver operation has been
      reported occasionally, fatal VAE in hepatic resection is uncommon. Prompt
      detection of VAE by transesophageal echocardiography (TEE) is crucial for
      effective therapy. We describe a case of fatal VAE that caused repeated cardiac
      arrest during hepatic resection and was confirmed by TEE. PATIENT CONCERNS: A 51
      year-old woman with a body weight of 50 kg underwent partial liver resection due
      to intrahepatic duct calculus. She had a 1-year history of intrahepatic duct
      calculus without cardiopulmonary disease. The operation was performed under
      general anesthesia combined with epidural block. When the inferior vena cava was
      compressed, the PetCO2 level decreased abruptly from 30 to 10 mmHg, followed by a
      decrease in SpO2 and the development of hypotension. Her heart rate increased
      with ST interval elevation on electrocardiography monitoring. Ephedrine and
      phenylephrine were administered immediately but had little effect. Cardiac arrest
      occurred. DIAGNOSES: Air embolism was detected by TEE. INTERVENTIONS:
      Resuscitation was successful although cardiac arrest occurred repeatedly.
      OUTCOMES: The patient returned to consciousness 6 hours postoperatively but died
      of multiorgan dysfunction 10 days later. LESSONS: Fatal air embolism may happen
      during hepatic resection. Prompt detection of VAE by TEE is crucial for effective
      therapy and should always be available during hepatic resection.

PMID- 30278588
TI  - ANRIL polymorphism rs4977574 is associated with increased risk of coronary artery
      disease in Asian populations: A meta-analysis of 12,005 subjects.
AB  - BACKGROUND: Several studies have shown that ANRIL polymorphism may be associated
      with the risk of coronary artery disease (CAD). However, these studies do not
      provide a clear consensus in Asian population. Thus, this meta-analysis was aimed
      to evaluate the relationship between the common variant rs4977574 in ANRIL and
      CAD risk in Asian population. METHODS: We conducted a systematic literature
      search of PubMed, Embase and the Cochrane Library and 2 Chinese databases. A
      total of 12,005 subjects from 6 independent studies were included. The pooled
      odds ratio (OR) and their corresponding 95% confidence intervals (CIs) were used
      to assess the association between rs4977574 and CAD using random effects model.
      RESULTS: A significant association was observed between rs4977574 and CAD risk
      under the allelic (OR: 1.18, 95% CI: 1.04-1.34, P = .010), recessive (OR: 1.27,
      95% CI: 1.01-1.60, P = .04), dominant (OR: 1.28, 95% CI: 1.13-1.44, P = .002),
      homozygous (OR: 1.46, 95% CI: 1.15-1.86, P = .002), and heterozygous model (OR:
      1.17, 95% CI: 1.07-1.28, P = .0004), especially in the Chinese subgroup and the
      myocardial infarction (MI) subgroup (P < .05). CONCLUSION: The ANRIL polymorphism
      rs4977574 is associated with CAD risk in Asian population. The rs4977574 with G
      allele may confer to a higher risk of CAD, especially MI.

PMID- 30278592
TI  - The why of neurological reflexes.

PMID- 30278591
TI  - Combination of the ankle-brachial index and percentage of mean arterial pressure
      to improve diagnostic sensitivity for peripheral artery disease: An observational
      study.
AB  - The ankle-brachial index (ABI) is a noninvasive method for screening for
      peripheral artery disease (PAD). However, false-negative findings of the ABI may
      limit its clinical use. The percentage of mean arterial pressure (%MAP)
      calculated from pulse volume recording has been reported to predict all-cause
      mortality. We hypothesized that the %MAP would be helpful to screen for PAD in
      subjects with a normal ABI. We examined whether using a combination of the ABI
      and %MAP would provide greater diagnostic sensitivity for PAD than using the ABI
      alone.In this cross-sectional study, we retrospectively reviewed the medical
      records of patients who had undergone multiple detector computed tomography
      (MDCT) angiography of the lower extremities following measurement of the ABI with
      pulse volume recording. PAD was diagnosed based on MDCT angiography.A total of
      215 lower extremities of 114 patients were included in our analyses. An optimal
      cut-off %MAP value of 42.5% was used to diagnose PAD based on MDCT in patients
      with an ABI > 0.90. Using a combination of an ABI < 0.90 and a %MAP >= 42.5% as
      diagnostic criteria for PAD resulted in better sensitivity (76.9%) than using the
      ABI alone (56.5% for an ABI < 0.90 and 63.4% for an ABI < 1.00). Using logistic
      regression analysis, we found that patients having both an ABI < 0.90 and an ABI
      > 0.90 with a %MAP >= 42.5% had a significantly higher risk of PAD than those
      having an ABI > 0.90 with a %MAP < 42.5% (odds ratio = 7.165, P = .006; odds
      ratio = 12.544, P < .001; respectively).Both the sensitivity and specificity were
      better when using a combination of an ABI <= 0.90 and a %MAP >= 42.5% than when
      using a low or borderline ABI. The %MAP is helpful for PAD screening in subjects
      with an ABI > 0.90.

PMID- 30278589
TI  - The relationship between oxidized low-density lipoprotein and related ratio and
      acute cerebral infarction.
AB  - This study aimed to study the value of oxidized low-density lipoprotein (OX-LDL)
      and related ratio in the diagnosis of acute cerebral infarction and the
      classification of acute cerebral infarction.Of the 129 patients enrolled in this
      study, 94 patients with acute cerebral infarction were assigned to the case
      group, and 35 healthy subjects were enrolled as control group (n = 35). And then
      the case group were divided into large-artery atherosclerosis (LAA) group (n =
      61) and small-artery occlusion (SAO) group (n = 33) according to the TOAST
      classification standard. Plasma OX-LDL levels were determined by enzyme-linked
      immunosorbent assay. OX-LDL/total cholesterol (OX-LDL/TC), OX-LDL/high-density
      lipoprotein (OX-LDL/HDL), OX-LDL/LDL were calculated.There were significant
      differences in OX-LDL, OX-LDL/TC, OX-LDL/HDL, and OX-LDL/LDL in patients with
      acute cerebral infarction and those in control group (P < .001). The area under
      the receiver-operating characteristic curve of OX-LDL and related ratio was >0.7
      (P < .001). There was a slight positive correlation between OX-LDL/TC and
      National Institutes of Health Stroke Scale score at admission (r = 0.265, P =
      .039) in the LAA group.OX-LDL, OX-LDL/TC, OX-LDL/HDL, and OX-LDL/LDL were closely
      related to acute cerebral infarction, especially with large atherosclerotic
      cerebral infarction. OX-LDL/TC can reflect the severity of acute cerebral
      infarction for LAA, but it cannot predict the short-term prognosis of acute
      cerebral infarction.

PMID- 30278594
TI  - Is importation of drugs from Canada the answer?

PMID- 30278595
TI  - The Long Birth and Short Life of The Recovery Navigation Program.

PMID- 30278590
TI  - Trends in conjunctivochalasis research from 1986 to 2017: A bibliometric
      analysis.
AB  - BACKGROUND: With the aging of the population and the use of video terminals, the
      incidence of Conjunctivochalasis is getting higher, and related research is
      increasing. So our research aimed to use visualization software to display the
      research trends of Conjunctivochalasis. METHODS: Retrieved the document (from
      1986 to 2017) of conjunctivochalasis in the web of science core collection,
      analyzed by Citespace V. RESULTS: The main language is English. Article is the
      key type of document. The average annual number of publications in the time
      period from 2008 to 2017 was 11.6, which was significantly higher than the period
      from 1994 to 2007, indicating that the total number of publications has been
      continuously developed. The law of frequency quoted showed an upward trend
      yearly. Furthermore, we can find out that Japan, USA, and People's Republic of
      China were the most productive countries, Kyoto Prefectural University of
      Medicine was the most prolific institution, Shanghai Jiaotong University is a key
      institution. The average IF of journals was 3.0508. Cornea and Canadian Journal
      of Ophthalmology are core journals. Tseng SCG is the most active scholar. All
      cited author contributed to 5 classifications. Di PMA paper is a classic
      literature. Huang YK paper can be regarded as the frontier document. All cited
      reference dedicated to 7 categories. Conjunctivochalasis is the hot topic,
      related to observe indicators, risk factors, treatment, graded diagnosis of
      conjunctivochalasis, etc. In addition, fibroblast was research hotspot. At
      length, the cluster map of keyword was divided into 7 categories. CONCLUSION:
      This research will help relevant clinicians and researchers to accurately and
      quickly grasp the research trends in the field, and continue to conduct new
      research on the basis.

PMID- 30278596
TI  - The Obstetrician/Gynecologist (OB/GYN): Revisiting the Past, Exploring the
      Present and Preparing for the Future.

PMID- 30278597
TI  - Prison: Pipeline to Women's Preventative Health.

PMID- 30278598
TI  - Perspective: Current Threats to Contraceptive Access.

PMID- 30278599
TI  - The Fourth Trimester of Pregnancy: Committing to Maternal Health and Well-Being
      Postpartum.
AB  - The postpartum period is a time of significant challenge and need as women adapt
      to hormonal and physical changes, recover from delivery, experience shifting
      family responsibilities, and endure sleep deprivation, all while caring for and
      nourishing their newborn. It is also a period of significant maternal health
      risk. Recent data on U.S. maternal mortality indicate a shift in the timing of
      maternal deaths over the past 10 years, with the majority of maternal deaths now
      occurring postpartum, from one day to one year after delivery. Postpartum care
      also marks a period of transition, as women shift from pregnancy-centered care to
      interpregnancy and primary care, yet current systems of care are marked by poor
      coordination of care between providers and patient care settings. Suboptimal
      postpartum follow-up is particularly worrisome for women with chronic health
      conditions or pregnancy complications who face both short- and long-term health
      risks. Given known challenges and medical risks, the single, 6-week postpartum
      visit women receive is woefully inadequate in addressing maternal health needs.
      Postpartum visits often fail to address the unique postpartum needs identified by
      mothers, inadequately connect women with primary care services, and have low
      attendance. Recognition of these unmet needs of "the Fourth Trimester" have led
      national organizations, including the American College of Obstetricians and
      Gynecologists (ACOG), to call for a restructuring of postpartum care to reduce
      postpartum and long-term morbidity and improve postpartum well-being. Rhode
      Island has several recent initiatives with the potential to improve outcomes for
      mother-baby dyads including the Baby Friendly Hospital Initiative (BFHI), the
      provision of long-acting reversible contraception (LARC) immediately postpartum,
      and the addition of HPV immunization postpartum. These initiatives remove
      barriers of access to care and provide vital women's health services prior to
      discharge. The Fourth Trimester provides a rich opportunity for maternal risk
      reduction and health promotion at a time when women are motivated and engaged
      with health care.

PMID- 30278600
TI  - On the Future of Maternal Mortality Review in Rhode Island.

PMID- 30278601
TI  - A Melting Pot of Medical Education: Challenges, solutions, and opportunities for
      improving trainee feedback and education in the ED.

PMID- 30278602
TI  - A Nearly 50% Decrease in New HIV Diagnoses in Rhode Island from 2006-2016:
      Implications for Policy Development and Prevention.
AB  - In the last decade, reductions in HIV incidence have been observed across the
      United States. However, HIV continues to disproportionately impact gay, bisexual,
      and other men who have sex with men (MSM). In Rhode Island, rates of HIV
      diagnoses have decreased by 44% across all groups over the last decade. This
      success has been the result of close collaboration across multiple sectors.
      Different prevention approaches, including syringe exchange programs, community
      based HIV testing, condom distribution, HIV care and treatment, and pre-exposure
      prophylaxis (PrEP) have all contributed to the decline in HIV diagnoses across
      the state. In 2015, Rhode Island became one of the first states to sign on to the
      Joint United Nations Programme on HIV/AIDS "90-90-90" campaign to end the HIV
      epidemic by 2030. Intensified and innovative initiatives are needed to improve
      progress in HIV prevention and treatment, especially in populations who are most
      at risk.

PMID- 30278603
TI  - Instability in Insurance Coverage: The Impacts of Churn in Rhode Island, 2014
      2017.
AB  - Churn, defined as a change in plan or a gap in insurance, is a problem in the
      United States that usually occurs as the result of changing life circumstances.
      Recent health reform perpetuates - rather than alleviates - churn because low-
      and middle- income individuals experience frequent changes in eligibility status.
      Our research asked: how common is churn in the non-group market and what are the
      health, financial, and emotional impacts on Rhode Island residents? This article
      draws examples from 31 life-history interviews and 188 enrollment observations
      conducted at Rhode Island's health insurance exchange from 2014-2017. The
      findings demonstrate that churn persists, despite state efforts to maximize
      enrollment, and causes poor health outcomes, financial insecurity, and increased
      stress. We argue that efforts to reform health insurance enrollment policies
      should be grounded in qualitative understandings of why people lose coverage and
      should seek to minimize barriers to maintaining continuous coverage.

PMID- 30278604
TI  - Financial Implications of Physician Specialty Choice.
AB  - PURPOSE: To examine the approximated financial outcomes of physicians by
      specialty and to determine whether these correlate with mean USMLE Step 1 scores.
      METHODS: Specialty-specific data from the Association of American Medical
      Colleges Careers in Medicine website were analyzed for total length of training,
      mean USMLE Step 1 scores, average hours worked per week, and median clinical
      practice salary for physicians. Hourly wage and estimated net worth at retirement
      were calculated. Coefficients of determination (R2) were calculated to evaluate
      the relationships between hourly wage, annual salary, and estimated net worth at
      retirement with competitiveness as measured by USMLE Step 1 scores of matched
      residents. RESULTS: Across all 37 specialties studied, the mean hourly wage was
      $136 +/- $40, ranging from $78 (Geriatrics) to $249 (Neurosurgery). Mean weekly
      hours worked across all specialties was 54.6 +/- 6.4, ranging from 43.4
      (Pediatric Emergency Medicine) to 71.1 (Vascular Surgery). At retirement, the
      mean estimated net worth for all physicians was $4,517,600 +/- $1,793,095,
      ranging from $1,927,779 (Child & Adolescent Psychiatry) to $8,947,885
      (Neurosurgery). Step 1 scores, as a marker of specialty competiveness, correlate
      with specialty compensation - the strongest association was with hourly wage (R2
      = 0.6678), then annual salary (R2 = 0.6424), and finally by estimated net worth
      at retirement (R2 = 0.6158). CONCLUSION: In this study, mean Step 1 scores for
      each medical specialty were positively correlated with compensation, including
      absolute salary, hourly wage and estimated net worth at retirement.

PMID- 30278605
TI  - Oral Health Concerns and Connections to Mental Health among Rhode Island High
      School Students, 2017.

PMID- 30278606
TI  - Studies on silk secretion in the trichoptera (F. Limnephilidae): I. Histology,
      histochemistry, and ultrastructure of the silk glands.
AB  - As part of a study on trichopteran silk secretion, the histology, histochemistry,
      and ultrastructure of the silk glands of two species of limnephilid trichopteran
      larvae, Pycnopsyche guttifer (Walk.) and Neophylax concinnus McL., were
      investigated. The silk glands consist of three anatomically distinct regions: a
      long, posterior silk-secreting region; a shorter, anterior conducting tube; and a
      terminal press/common duct. In Pycnopsyche, there is also a modified bulbous
      region between the secreting and conducting areas. Each anatomical region has a
      distinct cell type. There are two structurally and histochemically different
      components of the secretion in the glandular lumen: a core and a peripheral
      layer. Both components are produced all along the gland and are principally
      proteinaceous. However, the peripheral layer is also PAS and alcian blue (pH.
      2.5) positive and shows beta-metachromasia with toluidine blue (pH 3.5),
      indicating the presence of both neutral and acidic polysaccharides.

PMID- 30278607
TI  - Exocytosis of neurosecretory granules from the crustacean sinus gland in freeze
      fracture.
AB  - Exocytosis is clearly shown in freeze-fracture preparations to be the mechanism
      for neurosecretion granule release from axon endings in the crayfish sinus gland.
      The cytoplasmic leaflet (A-face) of axon ending membrane is characterized by
      randomly situated depressions representing invaginations of the axolemma, which
      are in contact with limiting membranes of neurohormone granules in the subjacent
      cytoplasm. The extracellular leaflet (B-face) of the axolemma at release sites
      exhibits complementary volcano-shaped protrusions which are cross-fractures
      through necks of channels formed by invaginating plasma membrane in contact with
      underlying neurosecretion granules. Structural variation in B-face protrusions is
      consistent with a spectrum of exocytotic profiles in various stages of formation,
      and with granules at different stages of passage out of the endings. Evidence in
      this study suggests that formation of exocytotic structures may begin by
      alteration of axon membrane structure at the neurosecretory ending-hemolymph
      interface prior to contact of the neurohormone granules with the axolemma.
      Limiting membranes of neurosecretory granules exhibit protrusions which appear to
      interconnect granules adjacent to release sites and to attach granules to the
      axolemma. Freeze-fracture is clearly shown to be an invaluable tool for
      monitoring the degree of exocytosis exhibited by sinus glands under normal
      conditions and under experimental acceleration of hormone release. This technique
      is capable therefore, of detecting slight increases in numbers of exocytotic
      profiles much more quickly and accurately than the examination of random thin
      sections.

PMID- 30278608
TI  - Truncated Core/NS3 Fusion Protein of HCV Adjuvanted with Outer Membrane Vesicles
      of Neisseria meningitidis Serogroup B: Potent Inducer of the Murine Immune System
AB  - Background: A licensed vaccine against hepatitis C virus (HCV) has not become
      available to date. The stability and antigenicity of a targeted synthesized
      recombinant fusion protein consisting of a truncated core and NS3 (rC/N) of HCV
      had been predicted. Although safe antigens, recombinant proteins are not
      efficacious vaccines without adjuvants. The present study evaluated the
      immunogenicity of rC/N as a bipartite antigen accompanied by Neisseria
      meningitidis serogroup B outer membrane vesicles (NMB OMVs) in BALB/c mice.
      Methods: The NMB OMVs were produced and evaluated accurately. The administrations
      were as follows: rC/N-OMV, rC/N-Freund's complete/incomplete adjuvant (CIA), rC/N
      MF59, rC/N, OMV, MF59, and PBS. The production of Th1 (IFN-gamma, IL-2)/Th2 (IL
      4)/Th17 (IL-17) cytokines and granzyme B (cytotoxic indicator) by splenic
      mononuclear cells and the humoral concentration of total IgG/IgG1 (Th2)/IgG2a
      (Th1) in sera of mice were measured using mouse ELISA kits. Results:
      Concentrations of Th1/Th2/Th17 cytokines, granzyme B, and  immunoglobulins in the
      spleens and sera of immunized mice, which had received antigen plus each adjuvant
      (rC/N-OMV, rC/N-Freund's CIA and rC/N-MF59), significantly raised compared to the
      controls (rC/N, OMV, MF59 and PBS). Th1-type responses were dominant over Th2
      type responses in vaccinated mice with rC/N-OMV, and Th2 type responses increased
      dominantly in vaccinated mice with rC/N-MF59 (p < 0.05). Discssion: NMB OMVs were
      able to increase Th1 immune responses dramatically more than MF59 and Freund's
      CIA. The formulation of rC/N with NMB OMVs showed its ability to induce Th1, Th2,
      and Th17 immune responses. rC/N-NMB OMVs is a promising approach for the
      development of an HCV therapeutic vaccine.

PMID- 30278609
TI  - Retraction of "Structural Basis for Antagonism by Suramin of Heparin Binding to
      Vaccinia Complement Protein".

PMID- 30278611
TI  - Retraction of "Structures of Apolipoprotein A-II and a Lipid-Surrogate Complex
      Provide Insights into Apolipoprotein-Lipid Interactions".

PMID- 30278610
TI  - Monolithically Integrated Perovskite Semiconductor Lasers on Silicon Photonic
      Chips by Scalable Top-Down Fabrication.
AB  - Metal-halide perovskites are promising lasing materials for the realization of
      monolithically integrated laser sources, the key components of silicon photonic
      integrated circuits (PICs). Perovskites can be deposited from solution and
      require only low-temperature processing, leading to significant cost reduction
      and enabling new PIC architectures compared to state-of-the-art lasers realized
      through the costly and inefficient hybrid integration of III-V semiconductors.
      Until now, however, due to the chemical sensitivity of perovskites, no
      microfabrication process based on optical lithography (and, therefore, on
      existing semiconductor manufacturing infrastructure) has been established. Here,
      the first methylammonium lead iodide perovskite microdisc lasers monolithically
      integrated into silicon nitride PICs by such a top-down process are presented.
      The lasers show a record low lasing threshold of 4.7 MUJcm-2 at room temperature
      for monolithically integrated lasers, which are complementary metal-oxide
      semiconductor compatible and can be integrated in the back-end-of-line processes.

PMID- 30278612
TI  - Protein Expression Landscape Defines the Differentiation Potential Specificity of
      Adipogenic and Myogenic Precursors in the Skeletal Muscle.
AB  - The balance of adipogenic and myogenic differentiation of skeletal muscle-derived
      mesenchymal stem cells is particularly important in muscle development and
      intramuscular fat deposition. This study aimed to explore the differential
      regulation between adipogenic and myogenic precursors by comparative analysis of
      their global proteome expression profile. Adipogenic and myogenic precursors
      isolated from neonatal porcine longissimus dorsi muscle by the preplate method
      were verified for their unique and distinct differentiation potential under
      myogenic or adipogenic induction. A total of 433 differentially expressed
      proteins (DEP) ( P < 0.05 and FC > 1.20 or <0.83) between adipogenic and myogenic
      precursors were detected via a tandem mass tag (TMT)-coupled LC-MS/MS approach,
      including 339 up-regulated and 94 down-regulated proteins in myogenic precursors
      compared with adipogenic precursors. On the basis of functional annotation and
      enrichment analysis of 433 DEP, adipogenic and myogenic precursors showed
      significantly different metabolic pattern of energy substances and differential
      regulations of gene expression, cell structure and development, ion homeostasis,
      and cell motility and migration. Three pathways including PPAR signaling pathway,
      phosphatidylinositol signaling system, and autophagy signaling pathway, which was
      differentially regulated between adipogenic and myogenic precursors, was also
      discovered to play crucial roles in cell differentiation. In conclusion, these
      differentiated regulation patterns between the two cell subsets of mesenchymal
      precursors together defines their differentiation potential specificity.

PMID- 30278614
TI  - From billiards to thermodynamic laws: Stochastic energy exchange model.
AB  - This paper studies a billiards-like microscopic heat conduction model, which
      describes the dynamics of gas molecules in a long tube with thermalized boundary.
      We numerically investigate the law of energy exchange between adjacent cells. A
      stochastic energy exchange model that preserves these properties is then derived.
      We further numerically justified that the stochastic energy exchange model
      preserves the ergodicity and the thermal conductivity of the original billiard
      model.

PMID- 30278615
TI  - Phase synchronization on spatially embedded duplex networks with total cost
      constraint.
AB  - Synchronization on multiplex networks has attracted increasing attention in the
      past few years. We investigate collective behaviors of Kuramoto oscillators on
      single layer and duplex spacial networks with total cost restriction, which was
      introduced by Li et al. [Phys. Rev. Lett. 104, 018701 (2010)] and termed as the
      Li network afterwards. We first explore how the topology of the network
      influences synchronizability of Kuramoto oscillators on single layer Li networks
      and find that the closer the Li network is to a regular lattice, the more
      difficult for it to evolve into synchronization. Then, we investigate
      synchronizability of duplex Li networks and find that the existence of inter
      layer interaction can greatly enhance inter-layer and global synchronizability.
      When the inter-layer coupling strength is larger than a certain critical value,
      inter-layer synchronization will always occur. Furthermore, on single layer Li
      networks, nodes with larger degrees reach global synchronization more easily than
      those with smaller degrees, while on duplex Li networks, due to inter-layer
      interaction, this phenomenon becomes much less obvious. The results are important
      for us to gain insight into collective behaviors of many real-world complex
      systems which inherently possess multiplex architecture.

PMID- 30278616
TI  - The modulation of multiple phases leading to the modified Korteweg-de Vries
      equation.
AB  - This paper seeks to derive the modified Korteweg-de Vries (mKdV) equation using a
      novel approach from systems generated from abstract Lagrangians possessing a two
      parameter symmetry group. The method utilises a modified modulation approach,
      which results in the mKdV emerging with coefficients related to the conservation
      laws possessed by the original Lagrangian system. Alongside this, an adaptation
      of the method of Kuramoto is developed, providing a simpler mechanism to
      determine the coefficients of the nonlinear term. The theory is illustrated using
      two examples of physical interest, one in stratified hydrodynamics and another
      using a coupled Nonlinear Schrodinger model, to illustrate how the criterion for
      the mKdV equation to emerge may be assessed and its coefficients generated.

PMID- 30278617
TI  - Hydrodynamic spin states.
AB  - We present the results of a theoretical investigation of hydrodynamic spin
      states, wherein a droplet walking on a vertically vibrating fluid bath executes
      orbital motion despite the absence of an applied external field. In this regime,
      the walker's self-generated wave force is sufficiently strong to confine the
      walker to a circular orbit. We use an integro-differential trajectory equation
      for the droplet's horizontal motion to specify the parameter regimes for which
      the innermost spin state can be stabilized. Stable spin states are shown to
      exhibit an analog of the Zeeman effect from quantum mechanics when they are
      placed in a rotating frame.

PMID- 30278618
TI  - Pilot-wave dynamics of two identical, in-phase bouncing droplets.
AB  - A droplet bouncing on the surface of a vibrating liquid bath can move
      horizontally guided by the wave it produces on impacting the bath. The wave
      itself is modified by the environment, and thus, the interactions of the moving
      droplet with the surroundings are mediated through the wave. This forms an
      example of a pilot-wave system. Taking the Oza-Rosales-Bush description for
      walking droplets as a theoretical pilot-wave model, we investigate the dynamics
      of two interacting identical, in-phase bouncing droplets theoretically and
      numerically. A remarkably rich range of behaviors is encountered as a function of
      the two system parameters, the ratio of inertia to drag, kappa , and the ratio of
      wave forcing to drag, beta . The droplets typically travel together in a tightly
      bound pair, although they unbind when the wave forcing is large and inertia is
      small or inertia is moderately large and wave forcing is moderately small. Bound
      pairs can exhibit a range of trajectories depending on parameter values,
      including straight lines, sub-diffusive random walks, and closed loops. The
      droplets themselves may maintain their relative positions, oscillate toward and
      away from one another, or interchange positions regularly or chaotically as they
      travel. We explore these regimes and others and the bifurcations between them
      through analytic and numerical linear stability analyses and through fully
      nonlinear numerical simulation.

PMID- 30278619
TI  - Effects of external forcing on evolutionary games in complex networks.
AB  - How did cooperation evolve in a complex network is an intensely investigated
      problem. Many mechanisms that promote cooperation have been proposed within the
      framework of the evolutionary game theory. Motivated by the fact that people in
      society or even a certain group are often controlled by a variety of simple
      rules, we present an external forcing mechanism to analyze the underlying reasons
      of widespread cooperation in this paper. In detail, we model the agents on a
      simple regular network, on which the learning method is controlled by external
      forcing mechanism, and prisoner's dilemma has been applied to describe the
      interaction of agents. By conducting large-scale Monte Carlo simulations, we can
      easily draw a conclusion that this mechanism can promote cooperation efficiently.
      In addition, we also show that the proposed mechanism is effective for the
      cooperation promotion for other game models, such as snowdrift game and
      multigames. Taken together, the mechanism of external forcing on the evolutionary
      game is a strong promoter of cooperation even under a severe temptation
      condition, which has a practical significance and will provide new insight into
      the analysis and control of cooperative strategy in the complex network for the
      further research.

PMID- 30278620
TI  - Efficient manifolds tracing for planar maps.
AB  - In this work, we introduce an exact calculation method and an approximation
      technique for tracing the invariant manifolds of unstable periodic orbits of
      planar maps. The exact method relies on an adaptive refinement procedure that
      prevents redundant calculations occurring in other approaches, and the
      approximated method relies on a novel interpolation approach based on normal
      displacement functions. The resulting approximated manifold is precise when
      compared to the exact one, and its relative computational cost falls like the
      inverse of the manifold length. To present the tracing method, we obtain the
      invariant manifolds of the Chirikov-Taylor map, and as an application we
      illustrate the transition from homoclinic to heteroclinic chaos in the Duffing
      oscillator that leads from localized chaos to global chaotic motion.

PMID- 30278621
TI  - Introduction to dynamics of manufacturing supply networks.
AB  - Manufacturing supply networks are complex dynamic networks that play a crucial
      role in the economy. Nevertheless, there are so far only few studies that apply
      modern tools of network science and dynamical system theory to the analysis of
      these networks. Here, we provide a brief introduction to these types of networks
      highlighting their basic organization, current challenges, and selected previous
      work. This paper serves as an introduction to a focus topic consisting of five
      papers by experts on supply network dynamics.

PMID- 30278622
TI  - Multilacunarity as a spatial multiscale multi-mass morphometric of change in the
      meso-architecture of plant parenchyma tissue.
AB  - The lacunarity index (monolacunarity) averages the behavior of variable size
      structures in a binary image. The generalized lacunarity concept
      (multilacunarity) on the basis of generalized distribution moments is an
      appealing model that can account for differences in the mass content at different
      scales. The model was tested previously on natural images [J. Vernon-Carter et
      al., Physica A 388, 4305 (2009)]. Here, the computational aspects of
      multilacunarity are validated using synthetic binary images that consist of
      random maps, spatial stochastic patterns, patterns with circular or polygonal
      elements, and a plane fractal. Furthermore, monolacunarity and detrended
      fluctuation analysis were employed to quantify the mesostructural changes in the
      intercellular air spaces of frozen-thawed parenchymatous tissue of pome fruit [N.
      A. Valous et al., J. Appl. Phys. 115, 064901 (2014)]. Here, the aim is to further
      examine the coherence of the multilacunarity model for quantifying the
      mesostructural changes in the intercellular air spaces of parenchymatous tissue
      of pome and stone fruit, acquired with X-ray microcomputed tomography, after
      storage and ripening, respectively. The multilacunarity morphometric is a
      multiscale multi-mass fingerprint of spatial pattern composition, assisting the
      exploration of the effects of metabolic and physiological activity on the pore
      space of plant parenchyma tissue.

PMID- 30278623
TI  - Walking droplets correlated at a distance.
AB  - Bouncing fluid droplets can walk on the surface of a vibrating bath forming a
      wave-particle association. Walking droplets have many quantum-like features.
      Research efforts are continuously exploring quantum analogues and respective
      limitations. Here, we demonstrate that two oscillating particles (millimetric
      droplets) confined to separate potential wells exhibit correlated dynamical
      features, even when separated by a large distance. A key feature is the
      underlying wave mediated dynamics. The particles' phase space dynamics is given
      by the system as a whole and cannot be described independently. Numerical phase
      space histograms display statistical coherence; the particles' intricate
      distributions in phase space are statistically indistinguishable. However,
      removing one particle changes the phase space picture completely, which is
      reminiscent of entanglement. The model here presented also relates to nonlinearly
      coupled oscillators where synchronization can break out spontaneously. The
      present oscillator-coupling is dynamic and can change intensity through the
      underlying wave field as opposed to, for example, the Kuramoto model where the
      coupling is pre-defined. There are some regimes where we observe phase-locking
      or, more generally, regimes where the oscillators are statistically
      indistinguishable in phase-space, where numerical histograms display their
      (mutual) most likely amplitude and phase.

PMID- 30278624
TI  - Walking droplets in a circular corral: Quantisation and chaos.
AB  - A millimetric liquid droplet may walk across the surface of a vibrating liquid
      bath through a resonant interaction with its self-generated wavefield. Such
      walking droplets, or "walkers," have attracted considerable recent interest
      because they exhibit certain features previously believed to be exclusive to the
      microscopic, quantum realm. In particular, the intricate motion of a walker
      confined to a closed geometry is known to give rise to a coherent wave-like
      statistical behavior similar to that of electrons confined to quantum corrals.
      Here, we examine experimentally the dynamics of a walker inside a circular
      corral. We first illustrate the emergence of a variety of stable dynamical states
      for relatively low vibrational accelerations, which lead to a double quantisation
      in angular momentum and orbital radius. We then characterise the system's
      transition to chaos for increasing vibrational acceleration and illustrate the
      resulting breakdown of the double quantisation. Finally, we discuss the
      similarities and differences between the dynamics and statistics of a walker
      inside a circular corral and that of a walker subject to a simple harmonic
      potential.

PMID- 30278625
TI  - Hong-Ou-Mandel-like two-droplet correlations.
AB  - We present a numerical study of two-droplet pair correlations for in-phase
      droplets walking on a vibrating bath. Two such walkers are launched toward a
      common point of intersection. As they approach, their carrier waves may overlap
      and the droplets have a non-zero probability of forming a two-droplet bound
      state. The likelihood of such pairing is quantified by measuring the probability
      of finding the droplets in a bound state at late times. Three generic types of
      two-droplet correlations are observed: promenading, orbiting, and chasing pair of
      walkers. For certain parameters, the droplets may become correlated for certain
      initial path differences and remain uncorrelated for others, while in other
      cases, the droplets may never produce droplet pairs. These observations pave the
      way for further studies of strongly correlated many-droplet behaviors in the
      hydrodynamical quantum analogs of bouncing and walking droplets.

PMID- 30278626
TI  - The interaction of a walking droplet and a submerged pillar: From scattering to
      the logarithmic spiral.
AB  - Millimetric droplets may walk across the surface of a vibrating fluid bath,
      propelled forward by their own guiding or "pilot" wave field. We here consider
      the interaction of such walking droplets with a submerged circular pillar. While
      simple scattering events are the norm, as the waves become more pronounced, the
      drop departs the pillar along a path corresponding to a logarithmic spiral. The
      system behavior is explored both experimentally and theoretically, using a
      reduced numerical model in which the pillar is simply treated as a region of
      decreased wave speed. A trajectory equation valid in the limit of weak droplet
      acceleration is used to infer an effective force due to the presence of the
      pillar, which is found to be a lift force proportional to the product of the
      drop's walking speed and its instantaneous angular speed around the post. This
      system presents a macroscopic example of pilot-wave-mediated forces giving rise
      to apparent action at a distance.

PMID- 30278627
TI  - Ratcheting droplet pairs.
AB  - Millimetric droplets may be levitated on the surface of a vibrating fluid bath.
      Eddi et al. [Europhys. Lett. 82, 44001 (2008)] demonstrated that when a pair of
      levitating drops of unequal size are placed nearby, they interact through their
      common wavefield in such a way as to self-propel through a ratcheting mechanism.
      We present the results of an integrated experimental and theoretical
      investigation of such ratcheting pairs. Particular attention is given to
      characterizing the dependence of the ratcheting behavior on the droplet sizes and
      vibrational acceleration. Our experiments demonstrate that the quantized inter
      drop distances of a ratcheting pair depend on the vibrational acceleration, and
      that as this acceleration is increased progressively, the direction of the
      ratcheting motion may reverse up to four times. Our simulations highlight the
      critical role of both the vertical bouncing dynamics of the individual drops and
      the traveling wave fronts generated during impact on the ratcheting motion,
      allowing us to rationalize the majority of our experimental findings.

PMID- 30278628
TI  - Complex spatiotemporal behavior and coherent excitations in critically-coupled
      chains of neural circuits.
AB  - We investigate a critically-coupled chain of nonlinear oscillators, whose
      dynamics displays complex spatiotemporal patterns of activity, including regimes
      in which glider-like coherent excitations move about and interact. The units in
      the network are identical simple neural circuits whose dynamics is given by the
      Wilson-Cowan model and are arranged in space along a one-dimensional lattice with
      nearest neighbor interactions. The interactions follow an alternating sign rule,
      and hence the "synaptic matrix" M embodying them is tridiagonal antisymmetric and
      has purely imaginary (critical) eigenvalues. The model illustrates the interplay
      of two properties: circuits with a complex internal dynamics, such as multiple
      stable periodic solutions and period doubling bifurcations, and coupling with a
      "critical" synaptic matrix, i.e., having purely imaginary eigenvalues. In order
      to identify the dynamical underpinnings of these behaviors, we explored a
      discrete-time coupled-map lattice inspired by our system: the dynamics of the
      units is dictated by a chaotic map of the interval, and the interactions are
      given by allowing the critical coupling to act for a finite period tau , thus
      given by a unitary matrix U=exp?(tau2M) . It is now explicit that such critical
      couplings are volume-preserving in the sense of Liouville's theorem. We show that
      this map is also capable of producing a variety of complex spatiotemporal
      patterns including gliders, like our original chain of neural circuits. Our
      results suggest that if the units in isolation are capable of featuring multiple
      dynamical states, then local critical couplings lead to a wide variety of
      emergent spatiotemporal phenomena.

PMID- 30278629
TI  - A coupled focusing-defocusing complex short pulse equation: Multisoliton,
      breather, and rogue wave.
AB  - Nonlinear Schrodinger equation, short pulse equation, and complex short pulse
      equation have important applications in nonlinear optics. They can be derived
      from the Maxwell equations. In this paper, we investigate a coupled focusing
      defocusing complex short pulse equation. The bright-bright, bright-dark, and dark
      dark soliton solutions of the coupled focusing-defocusing complex short pulse
      equation are constructed. Furthermore, the breather solutions are derived from
      the dark soliton solution. The rogue wave solutions are also constructed. The
      dynamics and the asymptotic behavior of the soliton solutions are analyzed, which
      reveals a fact that the bright-bright soliton collision can be either elastic or
      inelastic, but the bright-dark and dark-dark soliton collision can only be
      elastic.

PMID- 30278630
TI  - Standard map-like models for single and multiple walkers in an annular cavity.
AB  - Recent experiments on walking droplets in an annular cavity showed the existence
      of complex dynamics including chaotically changing velocity. This article
      presents models, influenced by the kicked rotator/standard map, for both single
      and multiple droplets. The models are shown to achieve both qualitative and
      quantitative agreement with the experiments, and make predictions about
      heretofore unobserved behavior. Using dynamical systems techniques and
      bifurcation theory, the single droplet model is analyzed to prove dynamics
      suggested by the numerical simulations.

PMID- 30278631
TI  - Bouncing droplet dynamics above the Faraday threshold.
AB  - We present the results of an experimental investigation of the dynamics of
      droplets bouncing on a vibrating fluid bath for forcing accelerations above the
      Faraday threshold. Two distinct fluid viscosity and vibrational frequency
      combinations (20 cS-80 Hz and 50 cS-50 Hz) are considered, and the dependence of
      the system behavior on drop size and vibrational acceleration is characterized. A
      number of new dynamical regimes are reported, including meandering, zig-zagging,
      erratic bouncing, coalescing, and trapped regimes. Particular attention is given
      to the regime in which droplets change direction erratically and exhibit a
      dynamics akin to Brownian motion. We demonstrate that the effective diffusivity
      increases with vibrational acceleration and decreases with drop size, as
      suggested by simple scaling arguments.

PMID- 30278632
TI  - Introduction to focus issue on hydrodynamic quantum analogs.
AB  - Hydrodynamic quantum analogs is a nascent field initiated in 2005 by the
      discovery of a hydrodynamic pilot-wave system [Y. Couder, S. Protiere, E. Fort,
      and A. Boudaoud, Nature 437, 208 (2005)]. The system consists of a millimetric
      droplet self-propeling along the surface of a vibrating bath through a resonant
      interaction with its own wave field [J. W. M. Bush, Annu. Rev. Fluid Mech. 47,
      269-292 (2015)]. There are three critical ingredients for the quantum like
      behavior. The first is "path memory" [A. Eddi, E. Sultan, J. Moukhtar, E. Fort,
      M. Rossi, and Y. Couder, J. Fluid Mech. 675, 433-463 (2011)], which renders the
      system non-Markovian: the instantaneous wave force acting on the droplet depends
      explicitly on its past. The second is the resonance condition between droplet and
      wave that ensures a highly structured monochromatic pilot wave field that imposes
      an effective potential on the walking droplet, resulting in preferred, quantized
      states. The third ingredient is chaos, which in several systems is characterized
      by unpredictable switching between unstable periodic orbits. This focus issue is
      devoted to recent studies of and relating to pilot-wave hydrodynamics, a field
      that attempts to answer the following simple but provocative question: Might
      deterministic chaotic pilot-wave dynamics underlie quantum statistics?

PMID- 30278633
TI  - Gravitational thermal flows of liquid metals in 3D variable cross-section
      containers: Transition from low-dimensional to high-dimensional chaos.
AB  - This study extends the numerical results presented in author's past work [M.
      Lappa and H. Ferialdi, Phys. Fluids 29(6), 064106 (2017)] about the typical
      instabilities of thermogravitational convection (the so-called Hadley flow) in
      containers with inclined (converging or diverging) walls. The flow is now allowed
      to develop along the third dimension (z). In a region of the space of parameters
      where the two-dimensional solutions were found to be relatively regular in time
      and with a simple structure in space (supporting transverse waves propagating
      either in the downstream or in the upstream direction), the 3D flow exhibits
      either waves traveling along the spanwise direction or spatially disordered and
      chaotic patterns. In order to identify the related mechanisms, we analyze the
      competition between hydrodynamic and hydrothermal (Oscillatory Longitudinal Roll)
      modes of convection for different conditions. A peculiar strategy of analysis is
      implemented, which, on the one hand, exploits the typical properties of systems
      developing coexisting branches of solutions ("multiple" states) and their
      sensitivity to a variation of the initial conditions and, on the other hand, can
      force such systems to select a specific category of disturbances (by enabling or
      disabling the related "physical" mechanisms). It is shown that hydrodynamic modes
      can produce early transition to chaos. The dimensionality of such states is
      investigated through evaluation of the "fractal" (correlation) dimension on the
      basis of the algorithm by Grassberger and Procaccia. When low-dimensional chaos
      is taken over by high-dimensional chaos, the flow develops a recognisable
      interval of scales where turbulence obeys the typical laws of the so-called
      "inertial range" and produces small-scale features in agreement with available
      Kolmogorov estimates.

PMID- 30278634
TI  - Mean field phase synchronization between chimera states.
AB  - We study two-layer networks of identical phase oscillators. Each individual layer
      is a ring network for which a non-local intra-layer coupling leads to the
      formation of a chimera state. The number of oscillators and their natural
      frequencies is in general different across the layers. We couple the phases of
      individual oscillators in one layer to the phase of the mean field of the other
      layer. This coupling from the mean field to individual oscillators is done in
      both directions. For a sufficient strength of this inter-layer coupling, the
      phases of the mean fields lock across the two layers. In contrast, both layers
      continue to exhibit chimera states with no locking between the phases of
      individual oscillators across layers, and the two mean field amplitudes remain
      uncorrelated. Hence, the networks' mean fields show phase synchronization which
      is analogous to the one between low-dimensional chaotic oscillators. The required
      coupling strength to achieve this mean field phase synchronization increases with
      the mismatches in the network sizes and the oscillators' natural frequencies.

PMID- 30278635
TI  - Effect of noise amplification during the transition to amplitude death in coupled
      thermoacoustic oscillators.
AB  - We present a systematic investigation of the effect of external noise on the
      dynamics of a system of two coupled prototypical thermoacoustic oscillators,
      horizontal Rijke tubes, using a mathematical model. We focus on the possibility
      of amplitude death (AD), which is observed in the deterministic model of coupled
      thermoacoustic oscillators as studied by Thomas et al. [Chaos 28, 033119 (2018)],
      in the presence of noise. Although a complete cessation of oscillations or AD is
      not possible in the stochastic case, we observe a significant reduction in the
      amplitude of coupled limit cycle oscillations (LCOs) with the application of
      strong coupling. Furthermore, as we increase the noise intensity, a sudden drop
      in the amplitude of pressure oscillations at the transition from LCO to AD,
      observed in the noise free case, is no longer discernible because of the
      amplification of noise in AD state. During this transition from LCO to AD, we
      notice a qualitative change in the distribution of the pressure amplitude from
      bimodal to unimodal. Furthermore, in order to demarcate the boundary of the
      transition from LCO and AD in the noisy case, we use 80 % suppression in the
      amplitude of LCO, which generally occurs in the parameter range over which this
      qualitative change in the pressure distribution happens, as a threshold. With the
      help of bifurcation diagrams, we show a qualitative change as well as a reduction
      in the size of amplitude suppression zones that happen due to the increase in
      noise intensity. We also observe the relative ease of suppressing the amplitude
      of LCO with time-delay coupling when detuning and dissipative couplings are
      introduced between the two thermoacoustic oscillators in the presence of noise.

PMID- 30278636
TI  - Synchronization of chimera states in a multiplex system of phase oscillators with
      adaptive couplings.
AB  - We study the interaction of chimera states in multiplex two-layer systems, where
      each layer represents a network of interacting phase oscillators with adaptive
      couplings. A feature of this study is the consideration of synchronization
      processes for a wide range of chimeras with essentially different properties,
      which are achieved due to the use of different types of coupling adaptation
      within isolated layers. We study the effect of forced synchronization of chimera
      states under unidirectional action between layers. This process is accompanied
      not only by changes in the frequency characteristics of the oscillators, but also
      by the transformation of the structure of interactions within the slave layer
      that become close to the properties of the master layer of the system. We show
      that synchronization close to identical is possible, even in the case of
      interaction of chimeras with essentially different structural properties (number
      and size of coherent clusters) formed by means of a relatively large parameter
      mismatch between the layers. In the case of mutual action of the layers in
      chimera states, we found a number of new scenarios of the multiplex system
      behavior along with those already known, when identical or different chimeras
      appear in both layers. In particular, we have shown that a fairly weak interlayer
      coupling can lead to suppression of the chimera state when one or both layers of
      the system demonstrate an incoherent state. On the contrary, a strong interlayer
      coupling provides a complete synchronization of the layer dynamics, accompanied
      by the appearance of multicluster states in the system's layers.

PMID- 30278637
TI  - Strange nonchaotic and chaotic attractors in a self-excited thermoacoustic
      oscillator subjected to external periodic forcing.
AB  - We experimentally investigate the synchronization dynamics of a self-excited
      thermoacoustic system forced beyond its phase-locked state. The system consists
      of a laminar premixed flame in a tube combustor subjected to periodic acoustic
      forcing. On increasing the forcing amplitude above that required for phase
      locking, we find that the system can transition out of phase locking and into
      chaos, which is consistent with the Afraimovich-Shilnikov theorem for the
      breakdown of a phase-locked torus. However, we also find some unexpected
      behavior, most notably the emergence of a strange nonchaotic attractor (SNA)
      before the onset of chaos. We verify the existence of the SNA and chaotic
      attractor by examining the correlation dimension, the autocorrelation function,
      the power-law scaling in the Fourier amplitude spectrum, the permutation entropy
      in a pseudoperiodic surrogate test, and the permutation spectrum. In summary,
      this study explores the SNA and chaotic dynamics of a thermoacoustic system
      forced beyond its phase-locked state, opening up new pathways for the development
      of alternative strategies to control self-excited thermoacoustic oscillations in
      combustion devices such as gas turbines and rocket engines.

PMID- 30278638
TI  - Faraday-Talbot effect: Alternating phase and circular arrays.
AB  - A hydrodynamic analog to the optical Talbot effect may be realized on the surface
      of a vertically shaken fluid bath when a periodic array of pillars protrudes from
      the fluid surface. When the pillar spacing is twice or one and a half times the
      Faraday wavelength, we observe repeated images of the pillars projected in front
      of the array. Sloshing inter-pillar ridges act as sources of Faraday waves,
      giving rise to self-images. Here, we explore the emergence of Faraday-Talbot
      patterns when the sloshing ridges between pillars have alternating phases. We
      present a simple model of linear wave superposition and use it to calculate the
      expected self-image locations, comparing them to experimental observations. We
      explore how alternating phase sources affect the Faraday-Talbot patterns for
      linear and circular arrays of pillars, where curvature allows for magnification
      and demagnification of the self-imaging pattern. The use of an underlying
      wavefield is a subject of current interest in hydrodynamic quantum analog
      experiments, as it may provide a means to trap walking droplets.

PMID- 30278639
TI  - A review of the theoretical modeling of walking droplets: Toward a generalized
      pilot-wave framework.
AB  - The walking droplet system has extended the range of classical systems to include
      several features previously thought to be exclusive to quantum systems. We review
      the hierarchy of analytic models that have been developed, on the basis of
      various simplifying assumptions, to describe droplets walking on a vibrating
      fluid bath. Particular attention is given to detailing their successes and
      failures in various settings. Finally, we present a theoretical model that may be
      adopted to explore a more generalized pilot-wave framework capable of further
      extending the phenomenological range of classical pilot-wave systems beyond that
      achievable in the laboratory.

PMID- 30278640
TI  - Delayed loss of stability due to the slow passage through Hopf bifurcations in
      reaction-diffusion equations.
AB  - This article presents the delayed loss of stability due to slow passage through
      Hopf bifurcations in reaction-diffusion equations with slowly-varying parameters,
      generalizing a well-known result about delayed Hopf bifurcations in analytic
      ordinary differential equations to spatially-extended systems. We focus on the
      Hodgkin-Huxley partial differential equation (PDE), the cubic Complex Ginzburg
      Landau PDE as an equation in its own right, the Brusselator PDE, and a spatially
      extended model of a pituitary clonal cell line. Solutions which are attracted to
      quasi-stationary states (QSS) sufficiently before the Hopf bifurcations remain
      near the QSS for long times after the states have become repelling, resulting in
      a significant delay in the loss of stability and the onset of oscillations.
      Moreover, the oscillations have large amplitude at onset, and may be spatially
      homogeneous or inhomogeneous. Space-time boundaries are identified that act as
      buffer curves beyond which solutions cannot remain near the repelling QSS, and
      hence before which the delayed onset of oscillations must occur, irrespective of
      initial conditions. In addition, a method is developed to derive the asymptotic
      formulas for the buffer curves, and the asymptotics agree well with the
      numerically observed onset in the Complex Ginzburg-Landau (CGL) equation. We also
      find that the first-onset sites act as a novel pulse generation mechanism for
      spatio-temporal oscillations.

PMID- 30278641
TI  - Exploring orbital dynamics and trapping with a generalized pilot-wave framework.
AB  - We explore the effects of an imposed potential with both oscillatory and
      quadratic components on the dynamics of walking droplets. We first conduct an
      experimental investigation of droplets walking on a bath with a central circular
      well. The well acts as a source of Faraday waves, which may trap walking droplets
      on circular orbits. The observed orbits are stable and quantized, with preferred
      radii aligning with the extrema of the well-induced Faraday wave pattern. We use
      the stroboscopic model of Oza et al. [J. Fluid Mech. 737, 552-570 (2013)] with an
      added potential to examine the interaction of the droplet with the underlying
      well-induced wavefield. We show that all quantized orbits are stable for low
      vibrational accelerations. Smaller orbits may become unstable at higher forcing
      accelerations and transition to chaos through a path reminiscent of the Ruelle
      Takens-Newhouse scenario. We proceed by considering a generalized pilot-wave
      system in which the relative magnitudes of the pilot-wave force and drop inertia
      may be tuned. When the drop inertia is dominated by the pilot-wave force, all
      circular orbits may become unstable, with the drop chaotically switching between
      them. In this chaotic regime, the statistically stationary probability
      distribution of the drop's position reflects the relative instability of the
      unstable circular orbits. We compute the mean wavefield from a chaotic trajectory
      and confirm its predicted relationship with the particle's probability density
      function.

PMID- 30278642
TI  - Time dependent stability margin in multistable systems.
AB  - We propose a novel technique to analyze multistable, non-linear dynamical
      systems. It enables one to characterize the evolution of a time-dependent
      stability margin along stable periodic orbits. By that, we are able to indicate
      the moments along the trajectory when the stability surplus is minimal, and even
      relatively small perturbation can lead to a tipping point. We explain the
      proposed approach using two paradigmatic dynamical systems, i.e., Rossler and
      Duffing oscillators. Then, the method is validated experimentally using the rig
      with a double pendulum excited parametrically. Both numerical and experimental
      results reveal significant fluctuations of sensitivity to perturbations along the
      considered periodic orbits. The proposed concept can be used in multiple
      applications including engineering, fluid dynamics, climate research, and
      photonics.

PMID- 30278643
TI  - High-dimensional dynamics in a single-transistor oscillator containing Feynman
      Sierpinski resonators: Effect of fractal depth and irregularity.
AB  - Fractal structures pervade nature and are receiving increasing engineering
      attention towards the realization of broadband resonators and antennas. We show
      that fractal resonators can support the emergence of high-dimensional chaotic
      dynamics even in the context of an elementary, single-transistor oscillator
      circuit. Sierpinski gaskets of variable depth are constructed using discrete
      capacitors and inductors, whose values are scaled according to a simple sequence.
      It is found that in regular fractals of this kind, each iteration effectively
      adds a conjugate pole/zero pair, yielding gradually more complex and broader
      frequency responses, which can also be implemented as much smaller Foster
      equivalent networks. The resonators are instanced in the circuit as one-port
      devices, replacing the inductors found in the initial version of the oscillator.
      By means of a highly simplified numerical model, it is shown that increasing the
      fractal depth elevates the dimension of the chaotic dynamics, leading to high
      order hyperchaos. This result is overall confirmed by SPICE simulations and
      experiments, which however also reveal that the non-ideal behavior of physical
      components hinders obtaining high-dimensional dynamics. The issue could be
      practically mitigated by building the Foster equivalent networks rather than the
      verbatim fractals. Furthermore, it is shown that considerably more complex
      resonances, and consequently richer dynamics, can be obtained by rendering the
      fractal resonators irregular through reshuffling the inductors, or even by
      inserting a limited number of focal imperfections. The present results draw
      attention to the potential usefulness of fractal resonators for generating high
      dimensional chaotic dynamics, and underline the importance of irregularities and
      component non-idealities.

PMID- 30278644
TI  - Bouncing ball on a vibrating periodic surface.
AB  - We present an investigation of a partially elastic ball bouncing on a vertically
      vibrated sinusoidal surface. Following the work of McBennett and Harris [Chaos
      26, 093105 (2016)], we begin by demonstrating that simple periodic vertical
      bouncing at a local minimum of the surface becomes unstable when the local
      curvature exceeds a critical value. The resulting instability gives rise to a
      period doubling cascade and results in persistent horizontal motion of the ball.
      Following this transition to horizontal motion, periodic "walking" states-where
      the ball bounces one wavelength over each vibration cycle-are possible and
      manifest for a range of parameters. Furthermore, we show that net horizontal
      motion in a preferred direction can be induced by breaking the left-right
      symmetry of the periodic topography.

PMID- 30278645
TI  - Delay Cournot duopoly models revisited.
AB  - In considering economic dynamics, it has been known that time delays are inherent
      in economic phenomena and could be crucial sources for oscillatory behavior. The
      main aim of this study is to shed light on what effects the delays can generate.
      To this end, different models of Cournot duopoly with different delays are built
      in a continuous time framework and their local and global dynamics are
      analytically and numerically examined. Three major findings are obtained. First,
      the stability switching conditions are analytically constructed. Second, it is
      numerically demonstrated that different lengths of the delays are sources for the
      birth of simple and complicated dynamics. Third, the delay for collecting
      information on the competitors' output alone does not affect stability.

PMID- 30278646
TI  - Dynamics, emergent statistics, and the mean-pilot-wave potential of walking
      droplets.
AB  - A millimetric droplet may bounce and self-propel on the surface of a vertically
      vibrating bath, where its horizontal "walking" motion is induced by repeated
      impacts with its accompanying Faraday wave field. For ergodic long-time dynamics,
      we derive the relationship between the droplet's stationary statistical
      distribution and its mean wave field in a very general setting. We then focus on
      the case of a droplet subjected to a harmonic potential with its motion confined
      to a line. By analyzing the system's periodic states, we reveal a number of
      dynamical regimes, including those characterized by stationary bouncing droplets
      trapped by the harmonic potential, periodic quantized oscillations, chaotic
      motion and wavelike statistics, and periodic wave-trapped droplet motion that may
      persist even in the absence of a central force. We demonstrate that as the
      vibrational forcing is increased progressively, the periodic oscillations become
      chaotic via the Ruelle-Takens-Newhouse route. We rationalize the role of the
      local pilot-wave structure on the resulting droplet motion, which is akin to a
      random walk. We characterize the emergence of wavelike statistics influenced by
      the effective potential that is induced by the mean Faraday wave field.

PMID- 30278647
TI  - Homoclinic-doubling and homoclinic-gluing bifurcations in the Takens-Bogdanov
      normal form with D4 symmetry.
AB  - In this paper, we investigate the dynamics of a fourth-order normal form near a
      double Takens-Bogdanov bifurcation. The reduced system of this normal form
      possesses eight pairs of homoclinic orbits for certain parameter values. The
      nonlinear time transformation method is applied to obtain an analytical
      approximation of the homoclinic orbit in the perturbed system and to construct
      the homoclinic bifurcation curve as well. Using numerical continuation, period
      doubling and homoclinic-doubling cascades emanating from a codimension-2
      bifurcation point are found. A codimension-2 homoclinic-gluing bifurcation point
      at which several homoclinic orbits concerning the origin glue together to form a
      new homoclinic orbit is also obtained. It is shown that in the vicinity of these
      bifurcation points, the system may exhibit chaos and chaotic attractors.

PMID- 30278649
TI  - A fractal-based approach for modeling stock price variations.
AB  - The recent global financial crisis has threatened the financial system with total
      collapse of many economic sectors with a particular penetration to world's stock
      markets. The large swings in the prices of international stocks or indexes have
      reinvigorated the debate on their mathematical modeling. The traditional
      approaches do not seem to be very exhaustive and satisfactory, especially when
      extreme events occur. We propose a fractal-based approach to model the actual
      prices by assuming that they follow a Multifractional Process with Random
      Exponent. An empirical evidence is offered that this stochastic process is able
      to provide an appropriate modeling of actual series in terms of goodness of fit
      by comparing three main stock indexes.

PMID- 30278648
TI  - Transition to chaos in wave memory dynamics in a harmonic well: Deterministic and
      noise-driven behavior.
AB  - A walker is the association of a sub-millimetric bouncing drop moving along with
      a co-evolving Faraday wave. When confined in a harmonic potential, its stable
      trajectories are periodic and quantised both in extension and mean angular
      momentum. In this article, we present the rest of the story, specifically the
      chaotic paths. They are chaotic and show intermittent behaviors between an
      unstable quantised set of attractors. First, we present the two possible
      situations we find experimentally. Then, we emphasise theoretically two
      mechanisms that lead to unstable situations. It corresponds either to noise
      driven chaos or low-dimensional deterministic chaos. Finally, we characterise
      experimentally each of these distinct situations. This article aims at presenting
      a comprehensive investigation of the unstable paths in order to complete the
      picture of walkers in a two dimensional harmonic potential.

PMID- 30278650
TI  - Interaction of two walkers: Perturbed vertical dynamics as a source of chaos.
AB  - Walkers are dual objects comprising a bouncing droplet dynamically coupled to an
      underlying Faraday wave at the surface of a vibrated bath. In this paper, we
      study the wave-mediated interaction of two walkers launched at one another, both
      experimentally and theoretically. Different outcomes are observed in which either
      the walkers scatter or they bind to each other in orbits or promenade-like
      motions. The outcome is highly sensitive to initial conditions, which is a
      signature of chaos, though the time during which perturbations are amplified is
      finite. The vertical bouncing dynamics, periodic for a single walker, is also
      strongly perturbed during the interaction, owing to the superposition of the wave
      contributions of each droplet. Thanks to a model based on inelastic balls coupled
      to the Faraday waves, we show that this perturbed vertical dynamics is the source
      of horizontal chaos in such a system.

PMID- 30278651
TI  - Dynamics of a binary mixture of non-spherical molecules: Test of hydrodynamic
      predictions.
AB  - We consider a new class of model systems to study systematically the role of
      molecular shape in the transport properties of dense liquids. Our model is a
      liquid binary mixture where both the molecules are non-spherical and
      characterized by a collection of parameters. Although in the real world most of
      the molecules are non-spherical, only a limited number of theoretical studies
      exist on the effects of molecular shapes and hardly any have addressed the
      validity of the hydrodynamic predictions of rotational and translational
      diffusion of these shapes in liquids. In this work, we study a model liquid
      consisting of a mixture of prolate and oblate (80:20 mixture) ellipsoids with
      interactions governed by a modified Gay-Berne potential for a particular aspect
      ratio (ratio of the length and diameter of the ellipsoids), at various
      temperature and pressure conditions. We report calculations of transport
      properties of this binary mixture by varying temperature over a wide range at a
      fixed pressure. We find that for the pressure-density conditions studied, there
      is no signature of any phase separation, except transitions to the crystalline
      phase at low temperatures and relatively low pressure (the reason we largely
      confined our studies to high pressure). We find that for our model binary
      mixture, both stick and slip hydrodynamic predictions break down in a major
      fashion, for both prolates and oblates and particularly so for rotation.
      Moreover, prolates and oblates themselves display different dynamical features in
      the mean square displacement and in orientational time correlation functions.

PMID- 30278652
TI  - Impulsive alignment of 4He-CH3I: A theoretical study.
AB  - We simulate the non-adiabatic laser alignment of the weakly bound 4He-CH3I
      complex based on a quantum mechanical wave packet calculation for a model He-CH3I
      interaction potential. Two different regimes are found depending on the laser
      intensity. At intensities typical of non-adiabatic alignment experiments, the
      rotational dynamics resembles that of the isolated molecule. This is attributed
      to the fact that after the initial prompt alignment peak the complex rapidly
      dissociates. The subsequent revival pattern is due to the free rotation of the
      molecule detached from the helium atom. It is superimposed to a flat background
      corresponding to ~20% of the wave packet which remains bound, containing lower
      rotational excitation. At lower intensities, dissociation is avoided but the
      rotational excitation is not high enough to provide an efficient alignment and a
      broad non-regular structure is observed. Besides, the interaction of the He atom
      with the molecule quenches any possible alignment. These interpretations are
      based on the calculation of different observables related to the rotational
      motion. We compare our findings with recent experimental and theoretical results
      of non-adiabatic alignment of linear molecules solvated in helium nanodroplets or
      weakly interacting with one helium atom.

PMID- 30278653
TI  - Erratum: "DAVIS: A direct algorithm for velocity-map imaging system" [J. Chem.
      Phys. 148, 194101 (2018)].

PMID- 30278654
TI  - Towards hybrid density functional calculations of molecular crystals via fragment
      based methods.
AB  - We introduce and employ two QM:QM schemes (a quantum mechanical method embedded
      into another quantum mechanical method) and report their performance for the X23
      set of molecular crystals. We furthermore present the theory to calculate the
      stress tensors necessary for the computation of optimized cell volumes of
      molecular crystals and compare all results to those obtained with various density
      functionals and more approximate methods. Our QM:QM calculations with
      PBE0:PBE+D3, PBE0:PBE+MBD, and B3LYP:BLYP+D3 yield at a reduced computational
      cost lattice energy errors close to the ones of the parent hybrid density
      functional method, whereas for cell volumes, the errors of the QM:QM scheme
      methods are in between the generalized gradient approximation and hybrid
      functionals.

PMID- 30278655
TI  - Computation of static quantum triplet structure factors of liquid para-hydrogen.
AB  - The instantaneous and centroid triplet structure factors, S(3)(k1,k2) , of liquid
      (one-center) para-hydrogen are computed on the crystallization line for
      temperatures T/K <= 33. The focus is on salient equilateral and isosceles
      features, and the methods utilized are path integral Monte Carlo (PIMC)
      simulations and Ornstein-Zernike (OZ) integral equations, which involve Jackson
      Feenberg convolution (JF3) and other distinct closures. Long path integral
      simulation runs are carried out in the canonical ensemble, so as to obtain
      sufficiently accurate direct PI triplet results. Conclusions are drawn regarding
      general triplet structure features and the role and usefulness of the OZ
      closures. The equilateral features are studied in more detail, and one finds that
      (a) PIMC results point to the existence of regularity in the centroid main peak
      amplitudes; (b) some of the studied closures give qualitative descriptions for
      wave numbers below k ~ 1 A-1, but they all fail to describe the main peak
      amplitude regions (1.75 < k/A-1 < 2.5); and (c) JF3 plays the role of a limit
      closure that is valid for increasing wave numbers (k >= 2.6 A-1). In addition,
      representative isosceles PI features turn out to be reasonably bounded (within
      Deltak = 0.1 A-1) by those of some closures.

PMID- 30278656
TI  - The thermodynamics of a liquid-solid interface at extreme conditions: A model
      close-packed system up to 100 GPa.
AB  - The first experimental insight into the nature of the liquid-solid interface
      occurred with the pioneering experiments of Turnbull, which simultaneously
      demonstrated both that metals could be deeply undercooled (and therefore had
      relatively large barriers to nucleation) and that the inferred interfacial free
      energy gamma was linearly proportional to the enthalpy of fusion [D. Turnbull, J.
      Appl. Phys. 21, 1022 (1950)]. By an atomistic simulation of a model face-centered
      cubic system via adiabatic free energy dynamics, we extend Turnbull's result to
      the realm of high pressure and demonstrate that the interfacial free energy,
      evaluated along the melting curve, remains linear with the bulk enthalpy of
      fusion, even up to 100 GPa. This linear dependence of gamma on pressure is shown
      to be a consequence of the entropy dominating the free energy of the interface in
      conjunction with the fact that the entropy of fusion does not vary greatly along
      the melting curve for simple monoatomic metals. Based on this observation, it
      appears that large undercoolings in liquid metals can be achieved even at very
      high pressure. Therefore, nucleation rates at high pressure are expected to be
      non-negligible, resulting in observable solidification kinetics.

PMID- 30278657
TI  - Low energy differential elastic electron scattering from acetonitrile (CH3CN).
AB  - Measurements of elastic differential cross sections for electron scattering from
      acetonitrile (CH3CN) have been performed utilizing a crossed electron-molecular
      beam experiment and with the relative flow method, for the incident electron
      energy range of 0.7 eV-30 eV and the scattering angle range of 10 degrees -130
      degrees . These differential cross sections have been used to calculate the
      elastic integral and momentum-transfer cross sections, revealing a pi * resonance
      located around 3 eV. The elastic differential cross sections are compared with
      available theoretical models using the R-matrix method and the Schwinger
      multichannel method.

PMID- 30278658
TI  - Statistical field theory for polar fluids.
AB  - Using a variational field-theoretic approach, we derive a theory for polar
      fluids. The theory naturally accounts for the reaction field without resorting to
      the cavity construct and leads to a simple formula for the dielectric constant in
      terms of the molecular dipole moment and density. We apply our formula to
      calculate the dielectric constants of nonpolarizable liquid models for more than
      a hundred small molecules without using any adjustable parameters. Our formula
      predicts dielectric constants of these nonpolarizable liquid models more
      accurately than the Onsager theory and previous field-theoretic dielectric
      theories, as demonstrated by the closer agreement to the simulation results. The
      general theory also yields the free energy, which can describe the response of
      polar fluids under applied electric fields.

PMID- 30278659
TI  - Coarse-grained modeling of multiphase interactions at microscale.
AB  - The objective of this study is to develop and test a coarse-grained molecular
      dynamics framework to model microscale multiphase systems with different inter
      particle interactions and recover emerging thermodynamic and mechanical
      properties at the microscale. A water-vapor model and a fused silica model are
      developed to demonstrate the capability of our framework. The former can
      reproduce the water density and surface tension over a wide range of
      temperatures; the latter can reproduce experimental density, tensile strength,
      and Young's modulus of fused silica. Therefore, the deformable solid model is
      implemented in the proposed framework. Validations of spatial scaling methods for
      solid, liquid, and multiphase systems suggest that the proposed framework can be
      calibrated at an arbitrary microscale and used at a different length scale
      without recalibration. Different values of wettability for a solid-liquid-vapor
      system that is characterized by the contact angle can be achieved by changing the
      solid-liquid inter-particle potential. Thanks to these features, the proposed
      coarse-grained molecular dynamics framework can potentially find applications in
      modeling systems in which multiple phases coexist and have substantial
      interactions.

PMID- 30278660
TI  - Density correlation in liquid surfaces: Bedeaux-Weeks high order terms and non
      capillary wave background.
AB  - We present Molecular Dynamics (MD) simulations of liquid-vapor surfaces, and
      their Intrinsic Sampling Method analysis, to get a quantitative test for the
      theoretical prediction of the capillary wave (CW) effects on density correlation
      done by Bedeaux and Weeks (BW) in 1985. The results are contrasted with
      Wertheim's proposal which is the first term in BW series and are complemented
      with a (formally defined and computational accessible) proposal for the
      background of non-CW fluctuations. Our conclusion is that BW theory is both
      accurate and needed since it may differ significantly from Wertheim's proposal.
      We discuss the implications for the analysis of experimental X-ray surface
      diffraction data and MD simulations.

PMID- 30278661
TI  - Microcanonical RT-TDDFT simulations of realistically extended devices.
AB  - In this paper, real-time time-dependent density functional theory (RT-TDDFT)
      calculations of realistically sized nanodevices are presented. These
      microcanonical simulations rely on a closed boundary approach based on recent
      advances in the software package CP2K. The obtained results are compared to those
      derived from the open-boundary Non-equilibrium Green's Function (NEGF) formalism.
      A good agreement between the "current vs. voltage" characteristics produced by
      both methods is demonstrated for three representative device structures, a carbon
      nanotube field-effect transistor, a GeSe selector for crossbar arrays, and a
      conductive bridging random-access memory cell. Different approaches to extract
      the electrostatic contribution from the RT-TDDFT Hamiltonian and to incorporate
      the result into the NEGF calculations are presented.

PMID- 30278662
TI  - Highly excited vibrational levels of methane up to 10 300 cm-1: Comparative study
      of variational methods.
AB  - In this work, we report calculated vibrational energy levels of the methane
      molecule up to 10 300 cm-1. Two potential energy surfaces constructed in quite
      different coordinate systems with different analytical representations are
      employed in order to evaluate the uncertainty of vibrational predictions. To
      calculate methane energy levels, we used two independent techniques of the
      variational method. One method uses an exact kinetic energy operator in internal
      curvilinear coordinates. Another one uses an expansion of Eckart-Watson nuclear
      motion Hamiltonian in rectilinear normal coordinates. In the Icosad range (up to
      five vibrational quanta bands-below 7800 cm-1), the RMS standard deviations
      between calculated and observed energy levels were 0.22 cm-1 and 0.41 cm-1 for
      these two quite different approaches. For experimentally well-known 3v3 sub
      levels, the calculation accuracy is estimated to be ~1 cm-1. In the Triacontad
      range (7660-9188 cm-1), the average error of the calculation is about 0.5 cm-1.
      The accuracy and convergence issues for higher energy ranges are discussed.

PMID- 30278663
TI  - Dielectric relaxation in acetamide + urea deep eutectics and neat molten urea:
      Origin of time scales via temperature dependent measurements and computer
      simulations.
AB  - Dielectric relaxation (DR) measurements in the frequency window 0.2 <= nu(GHz) <=
      50 for deep eutectic solvents (DESs) made of acetamide (CH3CONH2) and urea
      (NH2CONH2) with the general composition, [f CH3CONH2 + (1 - f) NH2CONH2] at f =
      0.6 and 0.7, reveal three distinct relaxation time scales-tau1 ~ 120 ps, tau2 ~
      40 ps, and tau3 ~ 5 ps. Qualitatively similar time scales have been observed for
      DR of neat molten urea, whereas the reported DR for neat molten acetamide in the
      same frequency window reflects two relaxation processes with no trace of ~100 ps
      time scale. This slowest DR time scale (tau1) resembles closely to the long-time
      constant of the simulated structural H-bond relaxation (CHB(t)) involving urea
      pairs. Similarity in activation energies estimated from the temperature dependent
      DR measurements (335 <= T/K <= 363) and structural H-bond relaxations indicates
      that the structural H-bond relaxation overwhelmingly dominates the slowest DR
      relaxation in these DESs. Simulated collective reorientational correlation
      functions (C l (t)), on the other hand, suggest that the second slower time scale
      (~40 ps) derives contributions from both the single particle orientation dynamics
      and structural H-bond relaxation, leaving no role for hydrodynamic molecular
      rotations. The sub-10 ps DR time scale has been found to be connected to the fast
      reorientation dynamics of the component molecules (acetamide or urea). Fractional
      viscosity dependence for the longest DR times, tauDR?eta/Tp , has been observed
      for these DESs with the fraction power p = 0.7. Subsequently, the temporal
      heterogeneity aspects of these media have been investigated by examining the
      simulated particle motion characteristics and substantiated by estimating the
      dynamically correlated time scales and length-scales through simulations of four
      point susceptibilities and density correlations. These estimated dynamical time
      scales and length-scales assist in explaining the different inferences regarding
      solution heterogeneity drawn from different measurements on these DESs.

PMID- 30278664
TI  - Unraveling the spectral signatures of solvent ordering in K-edge XANES of aqueous
      Na.
AB  - The aqueous solvation structure of the Na+ ion is studied both by molecular
      dynamics (MD) simulations and K-edge X-ray absorption near edge spectroscopy
      (XANES). We present a systematic study contrasting the differences in the
      predicted XANES spectra, using molecular configurations generated from classical
      and quantum MD. Using a set of suitable order parameters, we elucidate how the
      spectroscopic features are influenced by the local solvation structure around the
      Na+ ion. Our findings suggest that XANES is sensitive to fluctuations between the
      first and second solvation shells and can distinguish between classical and
      quantum interaction representations used to generate molecular ensembles.

PMID- 30278665
TI  - Long-range dispersion C6 coefficient for SF6 dimer: Experimental and theoretical
      study.
AB  - The long-range dispersion C6 coefficient for the SF6 dimer is experimentally
      measured using a technique that uses the expansion of a supersonic pulse jet into
      a vacuum. A dynamic model of the jet enables us to correlate the position of the
      maximal peak in the time-of-flight spectrum with the initial conditions of the
      experiment and the parameters of the intermolecular interaction potential. Due to
      the low temperature of the jet target, the C6 coefficient can be extracted
      directly from the experimental results. Theoretical calculation of the C6
      dispersion coefficient is also performed by using linearly approximated
      explicitly correlated coupled-cluster singles and doubles (CCSD(F12)) method with
      the subsequent utilization of the Casimir-Polder formula. Good agreement of
      experimental and theoretical results confirms the reliability of results.

PMID- 30278666
TI  - Effects of thermostatting in molecular dynamics on anharmonic properties of
      crystals: Application to fcc Al at high pressure and temperature.
AB  - The precision and accuracy of the anharmonic energy calculated in the canonical
      (NVT) ensemble using three different thermostats (viz., Andersen, Langevin, and
      Nose-Hoover) along with no thermostat (i.e., microcanonical, NVE) are compared
      via application to aluminum crystals at ~100 GPa for temperatures up to melting
      (4000 K) using ab initio molecular dynamics (AIMD) simulation. In addition to the
      role of the thermostat, the effect of using either conventional or the recently
      introduced harmonically mapped averaging (HMA) method is considered. The effect
      of AIMD time-step size Deltat on the ensemble averages gauges accuracy, while for
      a given Deltat, the stochastic uncertainty (computed using block averaging)
      provides the metric for precision. We identify the rate of convergence of block
      averages (with respect to block size) as an important issue in this context, as
      it imposes a minimum simulation length required to achieve reliable statistics,
      and it differs considerably among the methods. We observe that HMA with a
      Langevin thermostat in an NVT simulation shows the best performance, from the
      point of view of accuracy, precision, and simulation length. In addition, we
      introduce a novel HMA-based ensemble average for the temperature. In application
      to NVE simulations, the new formulation exhibits much smaller fluctuations
      compared to the conventional kinetic-energy approach; however, it provides only
      marginal improvement in uncertainty due to strong negative correlations exhibited
      by the conventional form (which acts to reduce its uncertainty but also slows
      convergence of the block averages).

PMID- 30278667
TI  - Experimental and theoretical investigations on the optical and electrochemical
      properties of pi-conjugated donor-acceptor-donor (DAD) compounds toward a
      universal model.
AB  - A series of nine (9) donor-acceptor-donor (DAD) pi-conjugated small molecules
      were synthesized via palladium catalyzed Stille aromatic cross-coupling reactions
      by the combination of six (6) heterocycle building blocks (thiophene, furan,
      thiazole, 2,1,3-benzothiadiazole, 2,1,3-pyridinothiadiazole, thienothiadiazole)
      acting as electron donating (thiazole, furan, thiophene) and electron deficient
      (benzothiadiazole, pyridinethiadiazole, thienothiadiazole) units. These model
      compounds enable determining the correspondence between the theoretical and
      experimental optical and electrochemical properties for the first time, via
      Density Functional Theory (DFT), time-dependent DFT, UV-Vis spectroscopy, and
      cyclic voltammetry, accordingly. The obtained theoretical models can be utilized
      for the design and synthesis of new DAD structures with precise optical bandgaps,
      absorption maxima, and energy levels suitable for different optoelectronic
      applications.

PMID- 30278668
TI  - Thermal behavior, structure, dynamic properties of aqueous glycine solutions
      confined in mesoporous silica MCM-41 investigated by x-ray diffraction and quasi
      elastic neutron scattering.
AB  - Differential scanning calorimetry, X-ray diffraction, and quasi-elastic neutron
      scattering (QENS) measurements of aqueous glycine solutions confined in
      mesoporous silica (MCM-41) were performed at different glycine concentrations,
      pH, and loading ratio (=mass of glycine solution/mass of dry MCM-41) in the
      temperature range from 305 to 180 K to discuss the confinement effect on the
      thermal behavior, the structure, and the dynamic properties of the solutions. The
      freezing points of the confined glycine solutions decreased, compared with those
      of the bulk solutions. The corresponding exothermic peak due to ice formation
      became broader with an increase in the glycine concentration. By subtracting X
      ray diffraction patterns of dry MCM-41 from those of glycine solution-loaded MCM
      41, information about the structure of the confined glycine solutions was
      obtained. The radial distribution functions of the confined glycine solutions
      showed that the peaks assigned to the interaction between glycine molecules and
      the surface silanol (Si-OH) groups of MCM-41 at pH = 5 were observed, in contrast
      to the case at pH = 2. The QENS data on H/D substituted aqueous glycine solutions
      gave the translational diffusion coefficients and the residence time of glycine
      and water molecules confined in MCM-41 individually. The activation energy of the
      diffusion coefficient of a glycine molecule at pH = 5 was larger than that at pH
      = 2. These results imply that glycine molecules locate near the pore surface of
      MCM-41 due to the formation of hydrogen bonding between glycine molecules and the
      silanol group of the MCM-41 wall at pH = 5.

PMID- 30278669
TI  - Communication: State-to-state inelastic scattering of interstellar O2 with H2.
AB  - Molecular oxygen (O2) is predicted to be a major reservoir of elemental oxygen in
      dense interstellar molecular clouds. However, the abundance of O2 derived from
      astronomical observations is much lower than expected. Solving the discrepancies
      between models and observations requires a review of the chemistry and
      collisional excitation of O2 in space. In particular, O2-H2 collisions are
      crucial to derive O2 abundance in space from the interstellar spectra. A crossed
      molecular beam experiment to probe the rotational excitation of O2 due to H2
      collisions at energies of 650 cm-1 is reported. Velocity map imaging was combined
      with state-selective detection of O2( X3Sigmag- ) by (2 + 1) resonance-enhanced
      multiphoton ionization. The obtained raw O2+ images were corrected from density
      to flux and the differential cross sections (DCSs) were then extracted. Exact
      quantum mechanical calculations were also performed. Very good agreement between
      experimental and theoretical DCSs was found. The agreement demonstrates our
      ability to determine inelastic processes between O2 molecules and H2 both
      theoretically and experimentally and that the excitation of O2 in the
      interstellar medium can be correctly modeled. Consequences on the astrophysical
      modeling are briefly evaluated.

PMID- 30278670
TI  - Optimized symmetry functions for machine-learning interatomic potentials of
      multicomponent systems.
AB  - Current machine-learning methods to reproduce ab initio potential energy
      landscapes suffer from an unfavorable computational scaling with respect to the
      number of chemical species. In this work, we propose a new approach by using
      optimized symmetry functions to explore similarities of structures in
      multicomponent systems in order to yield linear complexity. We combine these
      symmetry functions with the charge equilibration via neural network technique, a
      reliable artificial neural network potential for ionic materials, and apply this
      method to study alkali-halide materials MX with 6 chemical species (M = {Li, Na,
      K} and X = {F, Cl, Br}). Our results show that our approach provides good
      agreement both with experimental and DFT reference data of many physical and
      structural properties for any chemical combination.

PMID- 30278671
TI  - Dispersion in two-dimensional periodic channels with discontinuous profiles.
AB  - The effective diffusivity of Brownian tracer particles confined in periodic micro
      channels is smaller than the microscopic diffusivity due to entropic trapping.
      Here, we study diffusion in two-dimensional periodic channels whose cross section
      presents singular points, such as abrupt changes of radius or the presence of
      thin walls, with openings, delimiting periodic compartments composing the
      channel. Dispersion in such systems is analyzed using the Fick-Jacobs (FJ)
      approximation. This approximation assumes a much faster equilibration in the
      lateral than in the axial direction, along which the dispersion is measured. If
      the characteristic width a of the channel is much smaller than the period L of
      the channel, i.e., epsilon = a/L is small, this assumption is clearly valid for
      Brownian particles. For discontinuous channels, the FJ approximation is only
      valid at the lowest order in epsilon and provides a rough, though on occasions
      rather accurate, estimate of the effective diffusivity. Here we provide formulas
      for the effective diffusivity in discontinuous channels that are asymptotically
      exact at the next-to-leading order in epsilon. Each discontinuity leads to a
      reduction of the effective diffusivity. We show that our theory is consistent
      with the picture of effective trapping rates associated with each discontinuity,
      for which our theory provides explicit and asymptotically exact formulas. Our
      analytical predictions are confirmed by numerical analysis. Our results provide a
      precise quantification of the kinetic entropic barriers associated with profile
      singularities.

PMID- 30278672
TI  - Parent bending effects on nonadiabatic transition dynamics: Isotopomer-resolved
      imaging of photodissociation of CF3Br at two source temperatures.
AB  - Nonadiabatic transition between electronic states plays a critical role in the
      photodissociation of the CX3Y (X = H and F; Y = Cl, Br, and I) system, and the
      transition probability was considered to be closely related to the X-C-Y bending
      motion. Hereby the effect of F-C-Br bending vibration on the nonadiabatic
      transition dynamics is studied by time-sliced ion velocity imaging of
      Br(2P1/2,3/2) isotopomers produced from the photodissociation of title molecules
      at two source temperatures, 298 K and 473 K, respectively. At the photolysis
      wavelength 234 nm, the anisotropy parameter (beta) of the Br(2P3/2) products
      decreases from 1.3 at 298 K to 0.9 at 473 K, while the beta of Br(2P1/2) remains
      at almost 2 at two temperatures, indicating the significant effect of bending
      excitation on the ground channel. Two nonadiabatic dissociation pathways are
      suggested in the Br(2P3/2) channel. One of them is the parallel excitation from
      the ground state to the 3 Q 0 state in C3V symmetry, and then transition to the 1
      Q 1 state via conical intersection, and the other is the perpendicular excitation
      to the 3A' state in Cs symmetry and then decomposition along this state in the
      presence of the avoided crossing between 3A' and 4A' states. Closely related to
      the F-C-Br bending vibration of CF3Br is the latter transition.

PMID- 30278673
TI  - Influence of solvent quality on conformations of crowded polymers.
AB  - The structure and function of polymers in confined environments, e.g.,
      biopolymers in the cytoplasm of a cell, are strongly affected by macromolecular
      crowding. To explore the influence of solvent quality on conformations of crowded
      polymers, we model polymers as penetrable ellipsoids, whose shape fluctuations
      are governed by the statistics of self-avoiding walks, appropriate for a polymer
      in a good solvent. Within this coarse-grained model, we perform Monte Carlo
      simulations of mixtures of polymers and hard-nanosphere crowders, including trial
      changes in polymer size and shape. Penetration of polymers by crowders is
      incorporated via a free energy cost predicted by polymer field theory. To analyze
      the impact of crowding on polymer conformations in different solvents, we compute
      the average polymer shape distributions, radius of gyration, volume, and
      asphericity over ranges of the polymer-to-crowder size ratio and crowder volume
      fraction. The simulation results are accurately predicted by a free-volume theory
      of polymer crowding. Comparison of results for polymers in good and theta
      solvents indicates that excluded-volume interactions between polymer segments
      significantly affect crowding, especially in the limit of crowders much smaller
      than polymers. Our approach may help to motivate future experimental studies of
      polymers in crowded environments, with possible relevance for drug delivery and
      gene therapy.

PMID- 30278674
TI  - Efficient evaluation of the geometrical first derivatives of three-center Coulomb
      integrals.
AB  - The calculation of the geometrical derivatives of three-center electron repulsion
      integrals (ERIs) over contracted spherical harmonic Gaussians has been optimized.
      We compared various methods based on the Obara-Saika, McMurchie-Davidson, Gill
      Head-Gordon-Pople, and Rys polynomial algorithms using Cartesian, Hermite, and
      mixed Gaussian integrals for each scheme. The latter ERIs contain both Hermite
      and Cartesian Gaussians, and they combine the advantageous properties of both
      types of basis functions. Furthermore, prescreening of the ERI derivatives is
      discussed, and an efficient approximation of the Cauchy-Schwarz bound for first
      derivatives is presented. Based on the estimated operation counts, the most
      promising schemes were implemented by automated code generation, and their
      relative performances were evaluated. We analyzed the benefits of computing all
      of the derivatives of a shell triplet simultaneously compared to calculating them
      just for one degree of freedom at a time, and it was found that the former scheme
      offers a speedup close to an order of magnitude with a triple-zeta quality basis
      when appropriate prescreening is applied. In these cases, the Obara-Saika method
      with Cartesian Gaussians proved to be the best approach, but when derivatives for
      one degree of freedom are required at a time the mixed Gaussian Obara-Saika and
      Gill-Head-Gordon-Pople algorithms are predicted to be the best performing ones.

PMID- 30278675
TI  - The role of chain-stiffness in lattice protein models: A replica-exchange Wang
      Landau study.
AB  - Using Monte Carlo simulations, we investigate simple, physically motivated
      extensions to the hydrophobic-polar lattice protein model for the small (46 amino
      acid) protein Crambin. We use two-dimensional replica-exchange Wang-Landau
      sampling to study the effects of a bond angle stiffness parameter on the folding
      and uncover a new step in the collapse process for particular values of this
      stiffness parameter. A physical interpretation of the folding is developed by
      analysis of changes in structural quantities, and the free energy landscape is
      explored. For these special values of stiffness, we find non-degenerate ground
      states, a property that is consistent with behavior of real proteins, and we use
      these unique ground states to elucidate the formation of native contacts during
      the folding process. Through this analysis, we conclude that chain-stiffness is
      particularly influential in the low energy, low temperature regime of the folding
      process once the lattice protein has partially collapsed.

PMID- 30278676
TI  - Thermal conductivity of normal and deuterated water, crystalline ice, and
      amorphous ices.
AB  - The effect of deuteration on the thermal conductivity kappa of water, crystalline
      ice, and amorphous ices was studied using the pressure induced amorphization of
      hexagonal ice, ice Ih, to obtain the deuterated, D2O, forms of low-density
      amorphous (LDA), high-density amorphous (HDA), and very-high density amorphous
      (VHDA) ices. Upon deuteration, kappa of ice Ih decreases between 3% and 4% in the
      100-270 K range at ambient pressure, but the effect diminishes on densification
      at 130 K and vanishes just prior to amorphization near 0.8 GPa. The unusual
      negative value of the isothermal density rho dependence of kappa for ice Ih, g =
      (d ln kappa/d ln rho) T = -4.4, is less so for deuterated ice: g = -3.8. In the
      case of the amorphous ices and liquid water, kappa of water decreases by 3.5%
      upon deuteration at ambient conditions, whereas kappa of HDA and VHDA ices
      instead increases by up to 5% for pressures up to 1.2 GPa at 130 K, despite HDA's
      and VHDA's structural similarities with water. The results are consistent with
      significant heat transport by librational modes in amorphous ices as well as
      water, and that deuteration increases phonon-phonon scattering in crystalline
      ice. Heat transport by librational modes is more pronounced in D2O than in H2O at
      low temperatures due to a deuteration-induced redshift of librational mode
      frequencies. Moreover, the results show that kappa of deuterated LDA ice is 4%
      larger than that of normal LDA at 130 K, and both forms display an unusual
      temperature dependence of kappa, which is reminiscent of that for crystals (kappa
      ~ T -1), and a unique negative pressure dependence of kappa, which likely is
      linked to local-order structural similarities to ice Ih.

PMID- 30278677
TI  - A Finnish Meteorological Institute-Aerosol Cloud Interaction Tube (FMI-ACIT):
      Experimental setup and tests of proper operation.
AB  - The Finnish Meteorological Institute-Aerosol Cloud Interaction Tube (FMI-ACIT) is
      a multi-purpose instrument for investigating atmospherically relevant
      interactions between aerosol particles and water vapor under defined laboratory
      conditions. This work introduces an experimental setup of FMI-ACIT for
      investigation of the aerosol activation and the droplet growth under
      supersaturated conditions. Several simulations and experimental tests were
      conducted to find out what the proper operational parameters are. To verify the
      ability of FMI-ACIT to perform as a cloud condensation nuclei (CCN) counter,
      activation experiments were executed using size selected ammonium sulfate
      [(NH4)2SO4] particles in the size range of 10-300 nm. Supersaturations from 0.18%
      to 1.25% were tested by experiments with different temperature gradients. Those
      showed that FMI-ACIT can effectively measure CCN in this range. Measured droplet
      size distributions at supersaturations 0.18% and 1.25% are in good agreement with
      those determined by a droplet growth model.

PMID- 30278678
TI  - An atomistic model for the charge distribution in layered MoS2.
AB  - We present an atomistic model for predicting the distribution of doping electric
      charges in layered molybdenum disulfide (MoS2). This model mimics the charge
      around each ion as a net Gaussian-spatially distributed charge plus an induced
      dipole, and is able to predict the distribution of doping charges in layered MoS2
      in a self-consistent scheme. The profiles of doping charges in monolayer MoS2
      flakes computed by this charge-dipole model are in good agreement with those
      obtained by density-functional-theory calculations. Using this model, we
      quantitatively predict the charge enhancement in MoS2 monolayer nanoribbons, with
      which strong ionic charge-localization effects are shown.

PMID- 30278679
TI  - Non-equilibrium molecular-dynamics study of electromagnetic-field-induced propane
      hydrate dissociation.
AB  - Non-equilibrium molecular-dynamics simulations have been performed for
      dissolution of planar propane-hydrate/water interfaces in externally-applied
      electromagnetic (e/m) fields in the microwave to far infrared range (~2.45-200
      GHz) at electric-field intensities up to 2.0 V/nm and at roughly 20 K over/under
      temperatures vis-a-vis the zero-field propane-hydrate melting point. Upon e/m
      field application, there is a field-frequency threshold above which the
      dissociation rate drops significantly, with a plateau therein for larger
      frequencies. It was found that higher intensity and lower frequency facilitates
      dissociation. Except in the presence of a thermal driving-force, the 10 GHz
      frequency shows more substantial rate-enhancement effect vis-a-vis static
      electric fields or, indeed, lower-frequency e/m fields.

PMID- 30278680
TI  - Crucial role of fragmented and isolated defects in persistent relaxation of
      deeply supercooled water.
AB  - Properties of water have been well elucidated for temperatures above ~230 K and
      yet mysteries remain in the deeply supercooled region. By performing extensive
      molecular dynamics simulations on this supercooled region, we find that
      structural and dynamical instabilities are hidden in the experimentally
      inaccessible region between 235 K and 150 K. We find a hitherto undiscovered
      fragmentation from 220 K to 190 K, which is the breakup of large clusters
      consisting of molecules with a locally distorted tetrahedral structure into small
      pieces with one or two isolated defects. The fragmentation leads to considerable
      changes in the relaxation dynamics of water. We reveal a crucial role of specific
      three-coordinated defects in slow but persistent structural relaxation. The
      presence of relaxation due to these specific defects makes the water glass
      transition temperature T g (=136 K) extremely low and explains why the T g of
      water is ~1/2 of the melting temperature T m, much lower than the commonly obeyed
      2/3 rule of T g/T m.

PMID- 30278681
TI  - Non-equilibrium x-ray spectroscopy using direct quantum dynamics.
AB  - Advances in experimental methodology aligned with technological developments,
      such as 3rd generation light sources, X-ray Free Electron Lasers, and High
      Harmonic Generation, have led to a paradigm shift in the capability of X-ray
      spectroscopy to deliver high temporal and spectral resolution on an extremely
      broad range of samples in a wide array of different environments. Importantly,
      the complex nature and high information content of this class of techniques mean
      that detailed theoretical studies are often essential to provide a firm link
      between the spectroscopic observables and the underlying molecular structure and
      dynamics. In this paper, we present approaches for simulating dynamical processes
      in X-ray spectroscopy based upon on-the-fly quantum dynamics with a Gaussian
      basis set. We show that it is possible to provide a fully quantum description of
      X-ray spectra without the need of precomputing highly multidimensional potential
      energy surfaces. It is applied to study two different dynamical situations,
      namely, the core-hole lifetime dynamics of the water monomer and the dissociation
      of CF4+ recently studied using pump-probe X-ray spectroscopy. Our results compare
      favourably to previous experiments, while reducing the computational effort,
      providing the scope to apply them to larger systems.

PMID- 30278682
TI  - Chemical hardness: Temperature dependent definitions and reactivity principles.
AB  - In this brief report, we show that the three different chemical hardness
      definitions developed in the framework of the temperature-dependent density
      functional theory-namely, the electronic, the thermodynamic, and the Helmholtz
      hardnesses-imply both the hard and soft acids and bases (HSAB) principle and the
      maximum hardness (MH) principle. These hardnesses are identified as the second
      derivative of a thermodynamic state function and avoid the somewhat arbitrary
      approach, based on the parabolic interpolation of the energy versus electron
      number, that is normally used to justify these principles. This not only leads to
      a more mathematically sound justification of the HSAB and MH principles in the
      low-temperature limit but also establishes that the HSAB and the MH principles
      hold at any temperature of chemical relevance.

PMID- 30278683
TI  - A coherent derivation of the Ewald summation for arbitrary orders of multipoles:
      The self-terms.
AB  - In this work, we provide the mathematical elements we think essential for a
      proper understanding of the calculus of the electrostatic energy of point
      multipoles of arbitrary order under periodic boundary conditions. The emphasis is
      put on the expressions of the so-called self-parts of the Ewald summation where
      different expressions can be found in the literature. Indeed, such expressions
      are of prime importance in the context of new generation polarizable force field
      where the self-field appears in the polarization equations. We provide a general
      framework, where the idea of the Ewald splitting is applied to the electric
      potential and, subsequently, all other quantities such as the electric field, the
      energy, and the forces are derived consistently thereof. Mathematical well
      posedness is shown for all these contributions for any order of multipolar
      distribution.

PMID- 30278684
TI  - A new type of ionizer for charge-exchange particle analyzer.
AB  - The application of effective methods of charge-exchange neutral particle
      diagnostics to determine ion temperatures of plasmas in modern plasma
      installations is of great practical interest. In this paper, we propose a new
      type of ionizer based on ionization of neutral charge-exchange particles
      reflecting from metallic surfaces. A set of Ta plates is used as a reflecting
      surface converter. The experimental results of using the proposed ionizer on the
      T-10 tokamak installation are presented. The obtained ion temperature is compared
      with temperatures derived by other methods for ohmic plasma heating. It is shown
      that the determined ion temperature has an error of 10% and agrees well with
      values calculated by the Artsimovich formula and obtained by the active Charge
      eXchange Recombination Spectroscopy. The proposed analyzer for ion temperature
      determination has an enhanced sensitivity in comparison with other analyzers.

PMID- 30278685
TI  - Laboratory time-resolved X-ray diffractometry for investigation of reversible
      structural changes induced in single crystals by external electric field.
AB  - Time-resolved technique of X-ray diffraction curve measurement was implemented at
      a laboratory X-ray source using a high-speed data acquisition system. The time
      resolution of up to 100 us was achieved via this X-ray diffractometry technique
      in the experiment of rocking curve dynamics measurement in a piezoelectric
      lanthanum-gallium silicate crystal under the influence of high voltage periodic
      pulsed electric field with an amplitude of 3.08 kV/mm corresponding to the pre
      breakdown state. This perturbation caused a quick angular shift of the rocking
      curve caused by crystal lattice deformation due to the piezoelectric effect. The
      absence of the diffraction curve broadening effect was shown as well as the
      absence of the other significant relaxation-like variations of the curve
      parameters which are inherent for the migration of charge carriers (ions or
      vacancies) under the external electric field.

PMID- 30278686
TI  - A suite-level review of the neutron single-crystal diffraction instruments at Oak
      Ridge National Laboratory.
AB  - The nascent suite of single-crystal neutron diffractometers at the Oak Ridge
      National Laboratory has no equal at any other neutron scattering facility
      worldwide and offers the potential to re-assert single-crystal diffraction using
      neutrons as a significant tool to study nuclear and magnetic structures of small
      unit cell crystals, nuclear structures of macromolecules, and diffuse scattering.
      Signature applications and features of single-crystal neutron diffraction are
      high resolution nuclear structure analysis, magnetic structure and spin density
      determinations, contrast variation (particularly D2O/H2O) for nuclear structural
      studies, lack of radiation damage when using crystals of biological molecules
      such as proteins, and the fidelity to measure nuclear and magnetic diffuse
      scattering with elastic discrimination.

PMID- 30278687
TI  - WAND2-A versatile wide angle neutron powder/single crystal diffractometer.
AB  - Wide Angle Neutron Diffractometer Squared is a high-flux versatile diffractometer
      with a 2-Dimensional Position Sensitive Detector at the High Flux Isotope
      Reactor. The instrument has strengths in both powder and single crystal
      diffraction. It is a unique instrument in the neutron scattering landscape of
      North America, and its capabilities are at least equal to similar instruments in
      the world.

PMID- 30278688
TI  - Surface trap with dc-tunable ion-electrode distance.
AB  - We describe the design, fabrication, and operation of a novel surface-electrode
      Paul trap that produces a radio-frequency-null along the axis perpendicular to
      the trap surface. This arrangement enables control of the vertical trapping
      potential and consequentially the ion-electrode distance via dc-electrodes only.
      We demonstrate the confinement of single 40Ca+ ions at heights between 50 MUm and
      300 MUm above planar copper-coated aluminum electrodes. Laser-cooling and
      coherent operations are performed on both the planar and vertical motional modes.
      This architecture provides a platform for precision electric-field noise
      detection and trapping of vertical ion strings without excess micromotion and may
      have applications for scalable quantum computers with surface ion traps.

PMID- 30278689
TI  - A versatile apparatus for fermionic lithium quantum gases based on an
      interference-filter laser system.
AB  - We report on the design and construction of a versatile setup for experiments
      with ultracold lithium (Li) gases. We discuss our methods to prepare an atomic
      beam and laser cool it in a Zeeman slower and a subsequent magneto-optical trap,
      which rely on established methods. We focus on our laser system based on a stable
      interference-filter-stabilized, linear-extended-cavity diode laser, so far
      unreported for lithium wavelengths. Moreover, we describe our optical setup to
      combine various laser frequencies for cooling, manipulation, and detection of Li
      atoms. We characterize the performance of our system preparing degenerate samples
      of Li atoms via forced evaporation in a hybrid crossed-beam optical-dipole trap
      plus confining magnetic trap. Our apparatus allows one to produce quantum gases
      of N ~ 105...106 fermionic lithium-6 atoms at nanokelvin temperatures in cycle
      times below 10 s. Our optical system is particularly suited to study the dynamics
      of fermionic superfluids in engineered optical potentials.

PMID- 30278690
TI  - A high temperature gas flow environment for neutron total scattering studies of
      complex materials.
AB  - We present the design and capabilities of a high temperature gas flow environment
      for neutron diffraction and pair distribution function studies available at the
      Nanoscale Ordered Materials Diffractometer instrument at the Spallation Neutron
      Source. Design considerations for successful total scattering studies are
      discussed, and guidance for planning experiments, preparing samples, and
      correcting and reducing data is defined. The new capabilities are demonstrated
      with an in situ decomposition study of a battery electrode material under inert
      gas flow and an in operando carbonation/decarbonation experiment under reactive
      gas flow. This capability will aid in identifying and quantifying the atomistic
      configurations of chemically reactive species and their influence on underlying
      crystal structures. Furthermore, studies of reaction kinetics and growth pathways
      in a wide variety of functional materials can be performed across a range of
      length scales spanning the atomic to the nanoscale.

PMID- 30278691
TI  - A new method of out-of-focus millimeter wave imaging in fusion plasma diagnostics
      using Bessel beams.
AB  - Electron cyclotron emission imaging (ECEI) and microwave imaging reflectometry
      diagnostics have been employed on a number of magnetic fusion plasma confinement
      devices. The common approach is based on a Gaussian beam assumption, which
      generates good spatial resolution (centimeter level). However, the radial focal
      depth is limited by the poloidal resolution, which is comparable with the
      Rayleigh length (~150 mm). By contrast, a new Bessel beam approach has been
      developed and demonstrated to generate much longer focal depth with the property
      of propagation stability. To test the new approach, the DIII-D tokamak LCP ECEI
      optics have been re-designed to support a Bessel beam approach based on an axicon
      lens. The achievable radial coverage can exceed that of the current Gaussian
      approach by 3*. The imaging result is discussed in this paper based on the
      simulation analysis and laboratory testing result.

PMID- 30278692
TI  - Parallel 2D FFT implementation on FPGA suitable for real-time MR image
      processing.
AB  - We report the design and implementation of a parallel two-dimensional fast
      Fourier transform (2D FFT) algorithm on a Field Programmable Gate Array (FPGA)
      for real-time MR image processing. Although a number of architectures of 2D FFT
      hardware processors have been reported, these generic processors or IP cores are
      not always effective for processing MRI data. The key feature of our design is
      that our processors are customized solely for real-time MRI applications. We
      demonstrate that by considering the unique features of real-time MRI data
      streams, we were able to develop and implement the 2D FFT processors that are
      resource-efficient and flexible enough to handle both regular and irregular data.
      Using a data-driven approach, we were able to simplify the inter-processor data
      communication while maintaining data synchronization without a synchronous clock
      signal bus and complex interconnection network. We experimentally verified our
      designs by processing multi-slice image data sets with 128 * 128 and 256 * 256 in
      plane resolution. The results demonstrate the effectiveness of our 2D FFT
      processors and show that image reconstruction can be accelerated in proportion to
      the parallel processing factor. We achieved image-reconstruction processing rates
      up to 3000 and 800 slices per second for images with 128 * 128 and 256 * 256 in
      plane resolution, respectively. The results also indicate that the image
      reconstruction acceleration is primarily limited by the speed of the data
      transfer between the FPGA device and external sensors.

PMID- 30278693
TI  - Note: Simultaneous water quality monitoring and degradation of hazardous organic
      pollutants.
AB  - Here, we report a simple technique that uses mesoporous SnO2 to monitor the water
      quality and degrade the hazardous organic pollutants simultaneously. The
      technique generates hydroxyl radicals and a voltage that is hindered by the
      presence of hazardous organic pollutants. Pollutant as low as 1 ppb concentration
      level can easily be detected. The developed system not only monitors the water
      quality but also is capable of degrading hazardous dyes (organic pollutants)
      through its self-power, not relying on any external stimuli such as light, heat,
      radiation, and current. A simple digital laboratory multimeter is shown to be
      useful for the overall study. Overall, the study indicates that spectrophotometer
      generally used to monitor the dye concentration can be avoided.

PMID- 30278694
TI  - Time-of-flight neutron total scattering with applied electric fields: Ex situ and
      in situ studies of ferroelectric materials.
AB  - Characterizing the structural response of functional materials (e.g.,
      piezoelectrics and ferroelectrics) to electric fields is key for the creation of
      structure-property relationships. Here, we present a new sample environment and
      data reduction routines which allow the measurement of time-of-flight neutron
      total scattering during the in situ or ex situ application of high voltage (<10
      kV) to a sample. Instead of utilizing the entire detector space of the
      diffractometer, only selected regions of detector pixels with scattering at the
      desired angle to the sample electric field are interrogated, which allows the
      generation of orientation-dependent reciprocal space patterns and real-space pair
      distribution functions (PDFs). We demonstrate the method using the relaxor
      ferroelectric Na1/2Bi1/2TiO3 and observe lattice expansion parallel and
      contraction perpendicular to the electric field for both in situ and ex situ
      experiments, revealing the irreversible nature of the local scale structural
      changes to this composition. Additionally, changes in the distributions of
      nearest neighbor metal-oxygen bond lengths are observed, which have been
      difficult to observe in previously measured analogous orientation-dependent X-ray
      PDFs. Considerations related to sample positioning and background subtraction are
      discussed, and future research directions are suggested.

PMID- 30278696
TI  - Photometrics of ultrafast and fast broadband electronic transient absorption
      spectroscopy: State of the art.
AB  - The physical limits of the photometric resolution in broadband electronic
      transient absorption spectroscopy are discussed together with solutions for how
      to reach these limits in practice. In the first part, quantitative expressions
      for the noise contributions to the transient absorption signal are derived and
      experimentally tested. Experimental approaches described in the literature are
      discussed and compared on this basis. Guide-lines for designing a setup are
      established. In the second part, a method for obtaining nearly shot-noise limited
      kinetics with photometric resolution of the order of 100 MUOD in overall
      measurement times of a few minutes from femtosecond to microsecond time scale is
      presented. The results are discussed in view of other experiments of step-scan
      type which are subject to a background or to correlated noise. Finally, detailed
      information is provided on how to obtain transient absorption spectra where
      counting statistics are the sole source of noise. A method for how to suppress
      outliers without introducing bias is discussed. An application example is given
      to demonstrate the achievable signal-to-noise level and the fast acquisition
      time.

PMID- 30278695
TI  - Calibration and cross-laboratory implementation of scintillating screens for
      electron bunch charge determination.
AB  - We revise the calibration of scintillating screens commonly used to detect
      relativistic electron beams with low average current, e.g., from laser-plasma
      accelerators, based on new and expanded measurements that include higher charge
      density and different types of screens than previous work [Buck et al., Rev. Sci.
      Instrum. 81, 033301 (2010)]. Electron peak charge densities up to 10 nC/mm2 were
      provided by focused picosecond-long electron beams delivered by the Electron
      Linac for beams with high Brilliance and low Emittance (ELBE) at the Helmholtz
      Zentrum Dresden-Rossendorf. At low charge densities, a linear scintillation
      response was found, followed by the onset of saturation in the range of nC/mm2.
      The absolute calibration factor (photons/sr/pC) in this linear regime was
      measured to be almost a factor of 2 lower than that reported by Buck et al.
      retrospectively implying a higher charge in the charge measurements performed
      with the former calibration. A good agreement was found with the results provided
      by Glinec et al. [Rev. Sci. Instrum. 77, 103301 (2006)]. Furthermore long-term
      irradiation tests with an integrated dose of approximately 50 nC/mm2 indicate a
      significant decrease of the scintillation efficiency over time. Finally, in order
      to enable the transfer of the absolute calibration between laboratories, a new
      constant reference light source has been developed.

PMID- 30278697
TI  - Preface: Special Topic on Advances in Modern Neutron Diffraction at Oak Ridge
      National Laboratory.

PMID- 30278698
TI  - AGES: Automated Gas Environment System for in situ neutron powder diffraction.
AB  - High fluxes available at modern neutron and synchrotron sources have opened up a
      wide variety of in situ and operando studies of real processes using scattering
      techniques. This has allowed the user community to follow chemistry in the beam,
      which often requires high temperatures, gas flow, etc. In this paper, we describe
      an integrated gas handling system for the general-purpose powder diffraction
      beamline Powgen at the Spallation Neutron Source. The Automated Gas Environment
      System (AGES) allows control of both gas flow and temperature (room temperature
      to 850  degrees C), while measuring the partial pressure of oxygen and following
      the effluent gas by mass spectrometry, concurrent with neutron powder
      diffraction, in order to follow the structural evolution of materials under these
      conditions. The versatility of AGES is illustrated by two examples of experiments
      conducted with the system. In solid oxide fuel cell electrode materials, oxygen
      transport pathways in double perovskites PrBaCo2O5+delta and NdBaCo2O5+delta were
      elucidated by neutron diffraction measurements under atmosphere with oxygen
      partial pressures (pO2) of 10-1 to 10-4 (achieved using mixtures of nitrogen and
      oxygen) and temperatures from 575 to 850  degrees C. In another example, the
      potential oxygen storage material La1-xSrxFeO3 was measured under alternating
      flows of 15% CH4 in N2 and air (20% O2 in N2) at temperatures from 135 to 835 
      degrees C. From the oxygen stoichiometry, the optimal composition for oxygen
      storage was determined.

PMID- 30278699
TI  - Invited Article: Advances in tunable laser-based radiometric calibration
      applications at the National Institute of Standards and Technology, USA.
AB  - Recent developments at the National Institute of Standards and Technology's
      facility for Spectral Irradiance and Radiance responsivity Calibrations using
      Uniform Sources (SIRCUS) are presented. The facility is predicated on the use of
      broadly tunable narrow-band lasers as light sources in two key radiometric
      calibration applications. In the first application, the tunable lasers are used
      to calibrate the spectral power responsivities of primary standard detectors
      against an absolute cryogenic radiometer (ACR). The second function is to
      calibrate the absolute radiance and irradiance responsivities of detectors with
      uniform light sources, typically generated by coupling the laser light into
      integrating spheres. The radiant flux from the uniform sources is determined by
      the ACR-calibrated primary standard detectors. Together these sources and
      detectors are used to transfer radiometric scales to a variety of optical
      instruments with low uncertainties. We describe methods for obtaining the stable,
      uniform light sources required for low uncertainty measurements along with
      advances in laser sources that facilitate tuning over broader wavelength ranges.
      Example applications include the development of a detector-based thermodynamic
      temperature scale, the calibration and characterization of spectrographs, and the
      use of a traveling version of SIRCUS (T-SIRCUS) to calibrate large aperture Earth
      observing instruments and astronomical telescopes.

PMID- 30278700
TI  - Note: New method for high-space-resolving hotspot electron temperature
      measurements on Shenguang-III prototype.
AB  - High-space-resolving information of hotspot electron temperature is a foundation
      for further research on physical processes of implosion in inertial confinement
      fusion. This work proposed a novel high-space-resolving electron temperature
      detector, which is based on the bremsstrahlung radiation mechanism of the
      implosion hotspot and uses two-channel Kirkpatrick-Baez microscopes. In this
      novel detector, an optical quasi-coaxis method was used to eliminate the strong
      impact of the view field difference on the high space resolution and correctness
      of the electron temperature diagnosis, and a compound KB microscope method was
      proposed to reduce the number of spherical reflectors and save space.

PMID- 30278701
TI  - Note: A compact low-vibration high-performance optical shutter for precision
      measurement experiments.
AB  - The optical shutter is an important component for atom-interferometry-based
      precision measurements. To decrease its vibration noise and improve its
      performance, we present a compact design with a direct current motor and a
      photodetector inserted in a compact aluminum structure. The photodetector in the
      blade is driven by the motor to move either in or out of the way of the laser
      beam. This design can suppress laser intensity fluctuation down to 0.26% over 6 h
      in the method of sample and hold proportional-integral-derivative feedback. It is
      also quiet via an electrical braking process which not only reduces its vibration
      noise by an order of magnitude but also quickens and stabilizes its switching
      performance. The shutter has a switching time of 0.8 ms and an activation delay
      of 8 ms with low jitters. Besides, the shutter can work for over ten million
      cycles normally and reliably.

PMID- 30278702
TI  - An ultrahigh vacuum apparatus for H atom scattering from surfaces.
AB  - We present an apparatus to study inelastic H or D atom scattering from surfaces
      under ultra-high vacuum conditions. The apparatus provides high resolution
      information on scattering energy and angular distributions by combining a
      photolysis-based atom source with Rydberg atom tagging time-of-flight. Using
      hydrogen halides as precursors, H and D atom beams can be formed with energies
      from 500 meV up to 7 eV, with an energy spread of down to 2 meV and an intensity
      of up to 108 atoms per pulse. A six-axis manipulator holds the sample and allows
      variation of both polar and azimuthal incidence angles. Surface temperature can
      be varied from 45 K up to 1500 K. The apparatus' energy resolution (E/DeltaE) can
      be as high as 1000 and its angular resolution can be adjusted between 0.3 degrees
      and 3 degrees .

PMID- 30278703
TI  - Automated reactive accelerated aging for rapid in vitro evaluation of neural
      implant performance.
AB  - Novel therapeutic applications for neural implants require miniaturized devices.
      Miniaturization imposes stricter requirements for reliability of materials. Pilot
      clinical studies suggest that rapid failure of the miniaturized neural implants
      in the body presents a major challenge for this type of technology. Traditional
      evaluations of neural implant performance over clinically relevant durations
      present time- and resource-intensive experiments in animals. Reactive accelerated
      aging (RAA) is an in vitro test platform that was developed to expedite
      durability testing of neural implants, as a screening technique designed to
      simulate the aggressive physiological environment experienced by the implants.
      This approach employs hydrogen peroxide, which mimics reactive oxygen species,
      and a high temperature to accelerate chemical reactions that lead to device
      degradation similar to that found with devices implanted in vivo. The original
      RAA system required daily manual maintenance and was prone to variability in
      performance. To address these limitations, this work introduces automated
      reactive accelerated aging (aRAA) with closed-loop monitoring components that
      make the system simple, robust, and scalable. The core novel technology in the
      aRAA is electrochemical detection for feedback control of hydrogen peroxide
      concentration, implemented with simple off-the-shelf components. The aRAA can run
      multiple parallel experiments for high-throughput device testing and
      optimization. For this reason, the aRAA provides a simple tool for rapid in vitro
      evaluation of the durability of neural implants, ultimately expediting the
      development of a new generation of miniaturized devices with a long functional
      lifespan.

PMID- 30278704
TI  - A color x-ray camera for 2-6 keV using a mass produced back illuminated
      complementary metal oxide semiconductor sensor.
AB  - There are several reports in the scientific literature of the use of mass
      produced charge coupled device or complementary metal oxide semiconductor (CMOS)
      sensors as x-ray detectors that combine high spatial resolution with significant
      energy resolution. Exploiting a relatively new especially favorable ambient
      temperature back-illuminated CMOS sensor, we report the development of a
      spectroscopic x-ray camera having particularly impressive performance for 2-6 keV
      photons. This instrument has several beneficial characteristics for advanced x
      ray spectroscopy studies in the laboratory, at synchrotron light sources, at x
      ray free electron lasers, or when using pulsed x-ray sources such as for laser
      plasma physics research. These characteristics include fine position and energy
      resolution for individual photon events, high saturation rates, frame rates above
      100 Hz, easy user maintenance for damaged sensors, and software for real-time
      processing. We evaluate this camera as an alternative to traditional energy
      dispersive solid-state detectors, such as silicon drift detectors, and also
      illustrate its use in a very high resolution wavelength-dispersive x-ray
      fluorescence spectrometer (i.e., x-ray emission spectrometer) that has recently
      been reported elsewhere [W. M. Holden et al., Rev. Sci. Instrum. 88(7), 073904
      (2017)].

PMID- 30278705
TI  - A novel, tunable, multimodal microwave system for microwave reflectometry system.
AB  - Based on a new technique, a tunable, multi-channel system that covers the Q-band
      (33-55 GHz) is presented in this article. It has a potential use of the Doppler
      backscattering system diagnostic that can measure the turbulence radial
      correlation and the perpendicular velocity of turbulence by changing the incident
      angle. The system consists primarily of a double-sideband (DSB) modulation and a
      multiplier, which creates four probing frequencies. The probing frequency enables
      the simultaneous analysis of the density fluctuations and flows at four distinct
      radial regions in tokamak plasma. The amplitude of the probing frequency can be
      adjusted by the initial phase of the intermediate frequency (IF) input from the
      double-sideband, and the typical flatness is less than 10 dB. The system was
      tested in the lab with a rotating grating, and the results show that the system
      can operate in the frequency range of 33-55 GHz with a Q-band multitude and that
      the power of each channel can be adjusted by the phase of the IF input of DSB.

PMID- 30278706
TI  - Chemical-vapor deposited ultra-fast diamond detectors for temporal measurements
      of ion bunches.
AB  - This article reports on the development of thin diamond detectors and their
      characterization for their application in temporal profile measurements of
      subnanosecond ion bunches. Two types of diamonds were used: a 20 MUm thin
      polycrystalline chemical vapor deposited (CVD) diamond and a membrane with a
      thickness of (5 +/- 1) MUm etched out of a single crystal (sc) CVD diamond. The
      combination of a small detector electrode and an impedance matched signal outlet
      leads to excellent time response properties with a signal pulse resolution (FWHM)
      of tau = (113 +/- 11) ps. Such a fast diamond detector is a perfect device for
      the time of flight measurements of MeV ions with bunch durations in the
      subnanosecond regime. The scCVD diamond membrane detector was successfully
      implemented within the framework of the laser ion generation handling and
      transport project, in which ion beams are accelerated via a laser-driven source
      and shaped with conventional accelerator technology. The detector was used to
      measure subnanosecond proton bunches with an intensity of 108 protons per bunch.

PMID- 30278707
TI  - Note: Knife edge skimming for improved separation of molecular species by the
      deflector.
AB  - A knife edge for shaping a molecular beam is described to improve the spatial
      separation of the species in a molecular beam by the electrostatic deflector. The
      spatial separation of different molecular species from each other as well as from
      atomic seed gas is improved. The column density of the selected molecular-beam
      part in the interaction zone, which corresponds to higher signal rates, was
      enhanced by a factor of 1.5, limited by the virtual source size of the molecular
      beam.

PMID- 30278708
TI  - Multimode optical fiber photonic doppler velocimetery.
AB  - A new optical fiber head for Photonic Doppler Velocimetry (PDV) made from a
      combination of fiber types [multimode (MM) and single-mode (SM)] and lenses is
      described. The input laser beam is delivered by a SM fiber and imaged onto the
      target by simple optics, including an imaging lens centered inside a larger lens,
      whose role is to collect and image the back reflected light into the MM
      collection fiber. The large core of the MM fiber enhances the collection
      efficiency and also reduces its dependence on the target angle. Transmission
      through the MM fiber reduces the heterodyne fringe visibility considerably, but
      the Fourier analysis still enables very accurate resolution of the fringe
      frequency (and hence the velocity). The new PDV head with 20 GHz bandwidth was
      tested in a dynamical shock wave experiment to measure velocities of ~3 km/s
      (~3.9 GHz), and the results agreed very well with measurements by a standard SM
      PDV.

PMID- 30278709
TI  - Note: Optical filter method for high-resolution magnetostriction measurement
      using fiber Bragg grating under millisecond-pulsed high magnetic fields at
      cryogenic temperatures.
AB  - High-resolution magnetostriction measurement of DeltaL/L ~ 10-6 at a speed of 5
      MHz is performed using the optical filter method as the detection scheme for the
      fiber Bragg grating (FBG) based strain monitor under 35-ms pulsed high magnetic
      fields up to 45 T at 2.2 K. The resolution of magnetostriction is about the same
      order as the conventionally reported value from FBG based magnetostriction
      measurement systems for millisecond pulsed magnetic fields. The measurement speed
      is ~100 times the conventional ones. The present system can be a faster
      alternative for the conventional FBG based magnetostriction measurement system
      for millisecond pulsed high magnetic fields.

PMID- 30278710
TI  - A quasi-coaxial HV rolled pulse forming line.
AB  - A quasi-coaxial high-voltage (HV) rolled pulse forming line (rolled PFL) is
      researched in this paper. The PFL is rolled n circles on a support cylinder
      simultaneously by two layers of copper foil electrodes and two layers of
      insulation dielectrics. The first circle of the two electrodes are elicited in
      opposite directions along the axis, acting as the quasi-coaxial output structure
      of the PFL, and the left n - 1 circles of the PFL form a complete rolled strip
      line of n - 1 circles. The rolled PFL is convenient to realize HV insulation and
      is able to output a pulse with good quality. Characteristic parameters of the PFL
      are designed theoretically. Besides, the pulse discharge process of the PFL is
      simulated by computer simulation technology (CST) modeling, and the simulation
      result verifies the correctness of theory design. Furthermore, a rolled PFL with
      a characteristic impedance of 4.4 Omega is developed. The test characteristic
      impedance of the developed PFL by the incident pulse method confirms to the
      theory design. The discharge voltage waveform with a full width at half maximum
      of 57 ns of the PFL is acquired, which has a rise time of 6.8 ns. The HV test of
      the rolled PFL is carried out, and a discharge current pulse with an amplitude of
      7 kA is acquired when the PFL is charged to 70 kV. It is calculated that the
      developed PFL has an energy storage density of 2.5 J/l. A Tesla generator based
      on 13 stages of rolled PFLs is designed, which is expected to output a 450 kV
      pulse with a duration of 100 ns on a 40-Omega match load. The discharge waveform
      of the generator is simulated by the CST software. The simulative output pulse
      has a rise time of 5 ns, with a flattop jitter less than 5%.

PMID- 30278711
TI  - Suppression of higher diffraction orders in the extreme ultraviolet range by a
      reflective quasi-random square nano-pillar array.
AB  - Higher diffraction orders of a grating introduce so-called harmonics
      contamination that leads to ambiguity in the spectral data. They are also present
      in "monochromatic" output beams processed by grating monochromators at
      synchrotron radiation facilities, making calibration results of optical elements
      and detectors imprecise. The paper describes a new design of a reflective quasi
      random square nano-pillar array grating to reduce the amount of data of the
      grating relief pattern that is 10 cm in size and suppresses higher diffraction
      orders in the extreme ultraviolet range. In addition, a laboratory-scale grating
      monochromator equipped with the grating has been developed to test its
      spectroscopy characteristics at grazing incidence. The results illustrate that it
      can suppress higher diffraction orders and maintain the spectral resolving power
      as an ordinary grating at grazing incidence. The grating has great potential in
      harmonics suppression in the field of synchrotron radiation, spectral diagnostics
      of plasma, and astrophysics.

PMID- 30278712
TI  - An angular-resolved multi-channel Thomson parabola spectrometer for laser-driven
      ion measurement.
AB  - A multi-channel Thomson parabola spectrometer was designed and employed to
      diagnose ion beams driven by intense laser pulses. Angular-resolved energy
      spectra for different ion species can be measured in a single shot. It contains
      parallel dipole magnets and wedged electrodes to fit ion dispersion of different
      charge-to-mass ratios. The diameter and separation of the entrance pinhole
      channels were designed properly to provide sufficient resolution and avoid
      overlapping of dispersed ion beams. To obtain a precise energy spectral
      resolving, three-dimensional distributions of the electric and magnetic fields
      were simulated. Experimental measurement of energy-dependent angular
      distributions of target normal sheath accelerated protons and deuterons was
      demonstrated. This novel compact design provides a comprehensive characterization
      for ion beams.

PMID- 30278713
TI  - Non-perturbing THz generation at the Tsinghua University Accelerator Laboratory
      31 MeV electron beamline.
AB  - In recent experiments at Tsinghua University Accelerator Laboratory, the 31 MeV
      electron beam, which has been compressed to subpicosecond pulse durations, has
      been used to generate high peak power, narrow band Terahertz (THz) radiation by
      transit through different slow wave structures, specifically quartz capillaries
      metallized on the outside. Despite the high peak powers that have been produced,
      the THz pulse energy is negligible compared to the energy of the electron beam.
      Therefore, the THz generation process can be complementary to other beamline
      applications like plasma wakefield acceleration studies and Compton x-ray free
      electron lasers. This approach can be used at x-ray free electron laser
      beamlines, where THz radiation can be generated without disturbing the x-ray
      generation process. In the experiment reported here, a high peak current electron
      beam generated strong narrow band (~1% bandwidth) THz signals in the form of a
      mixture of TM01 and TM02 modes. Each slow wave structure is completed with a mode
      converter at the end of the structure that allows for efficient (>90%) power
      extraction into free space. In the experiment, both modes in these two dielectric
      loaded waveguides TM01 (0.3 THz/0.5 THz) and TM02 (0.9 THz/1.3 THz) were
      explicitly measured with an interferometer. The THz pulse energy was measured
      with a calibrated Golay cell at a few MUJ.

PMID- 30278714
TI  - Note: Controlling the length of plasmonic tips obtained by pulsed electrochemical
      etching.
AB  - We present a method to control the length of plasmonic gold tips through pulsed
      electrochemical etching. This method uses a cut-off circuit to interrupt the
      etching when the desired length is achieved, paving the way to tune the plasmonic
      properties of these tips through their shape. The control of the tip length by
      monitoring the cell voltage is the result of a study of the etching dynamics. The
      resulting tips possess a low apex radius and a small opening angle, allowing for
      high spatial resolution both in topography and in near-field imaging. The
      plasmonic behavior was confirmed in tip-enhanced Raman spectroscopy.

PMID- 30278715
TI  - A pressure-tuned Fabry Perot interferometer for laser frequency stabilization and
      tuning.
AB  - We present a simple, inexpensive pressure-tuned Fabry Perot interferometer which
      can be used to frequency stabilize and tune a laser when no suitable atomic
      reference is available. Our design, made largely from off-the-shelf parts, yields
      a tuning range of about 4 GHz and offers an absolute tuning accuracy of better
      than 1 MHz. The interferometer, which uses air as its working medium, is
      characterized by a low thermal drift rate of order 1 MHz per hour.

PMID- 30278716
TI  - Note: Development of a triple resonance pulse transformer based on magnetic core
      transformer.
AB  - In this paper, a triple resonance pulse transformer based on a magnetic core
      transformer is developed, which uses the first peak of the output voltage to
      charge the load capacitor. A compact magnetic core pulse transformer is
      developed, which uses an innovative bi-conical specific geometry. Based on this
      magnetic core pulse transformer, the triple resonance circuit is built by adding
      a tuning capacitor and a tuning inductor between this transformer and a pulse
      forming line (PFL). The tuning capacitor is designed to be an irregular coaxial
      capacitor with a capacitance of 70 pF and the tuning inductor is made as a single
      layer air core cylindrical inductor. The experimental results indicate that the
      peak output voltage of the triple resonance pulse transformer is about 530 kV and
      the rise time is about 790 ns. The peak voltage across PFL is 1.6 times the peak
      voltage across the magnetic core transformer. It is feasible to develop a
      magnetic core pulse transformer into a triple resonance pulse transformer.

PMID- 30278717
TI  - Note: Observation of the angular distribution of an x-ray characteristic emission
      through a periodic multilayer.
AB  - We present the observation of the angular distribution of a characteristic x-ray
      emission through a periodic multilayer. The emission coming from the substrate on
      which the multilayer is deposited is used for this purpose. It is generated upon
      proton irradiation through the multilayer and detected with an energy sensitive
      CCD camera. The observed distribution in the low detection angle range presents a
      clear dip at a position characteristic of the emitting element. Thus, such a
      device can be envisaged as a spectrometer without mechanical displacement and
      using various ionizing sources (electrons, x-rays, and ions), their incident
      direction being irrelevant.

PMID- 30278718
TI  - Implementation of ultraviolet Thomson scattering on SG-III laser facility.
AB  - An ultraviolet Thomson-scattering system has been designed and implemented on the
      Shenguang-III laser facility, a 48-beam, 3omega (351 nm), 180 kJ-level laser
      driver for high energy density physics and inertial confinement fusion
      researches. The 4omega (263.3 nm) probe beam of the Thomson-scattering system is
      injected from the north pole (top) of the target chamber, with an assistant beam
      pointing monitor to achieve high pointing accuracy. The Thomson-scattered light
      is collected by a double-Cassegrain optical transmission system, which provides
      an achromatic image over a wide wavelength range of 200-800 nm. A novel on-line
      alignment method is developed and applied to the diagnostic system, ensuring a
      volumetric positioning accuracy of ~30 MUm for the scattering volume. An online
      calibration is also conducted to provide the wavelength benchmark and the
      spectral resolution of the system. This Thomson-scattering system has been tested
      in a complicated experimental environment with gas-filled hohlraums, and a high
      quality ion feature of the scattered light has been obtained.

PMID- 30278719
TI  - A 30 GW subnanosecond solid-state pulsed power system based on generator with
      semiconductor opening switch and gyromagnetic nonlinear transmission lines.
AB  - This article describes a subnanosecond solid-state pulsed power system in which
      an input pulse from a generator with a semiconductor opening switch (generator)
      is amplified in power and is shortened in time by a two-stage magnetic compressor
      based on gyromagnetic nonlinear transmission lines. In this approach, the line of
      each stage operates as a magnetic compression line (MCL) which is realized when
      the duration of the input pulse is close to the period of oscillations generated
      by the line. The compression system contains two series connected lines MCL1 and
      MCL2 with a wave impedance of 40 Omega. The input pulse has a duration of 7 ns
      and an amplitude of 500 kV. After two compression stages, the pulse amplitude
      increases to 1.1 MV and the peak power increases from 6 to 30 GW, while the pulse
      duration transits into subnanosecond range (0.65 ns). In the burst mode, the
      system operates at a pulse repetition frequency up to 1 kHz.

PMID- 30278720
TI  - An actively shielded gradient coil design for use in planar MRI systems with
      limited space.
AB  - In planar magnetic resonance imaging (MRI) systems, gradient coils are usually
      placed within a very limited space owing to the physical constraints of the small
      gap size (pole-pole) distance of the permanent magnet. Typically, the unshielded
      or partially shielded design scheme is adopted to generate required magnetic
      fields with reduced system costs. However, non-fully shielded coils can induce
      large eddy currents on the surrounding metal structures, including magnet poles,
      that significantly impact the imaging performance. This paper elaborates a new
      design strategy to resolve the limited space problem. Using the peripheral
      sections of the MRI system, a set of actively shielded gradient coils are
      purposefully designed. Between the two magnet poles, the actively shielded
      gradient coils occupy merely four coil layers (six coil layers are usually
      required), which offers an excellent shielding effect, thus reducing the image
      distortions. The saved space can be used to integrate a high-efficient cooling
      system. Moreover, the design scheme does not significantly increase the
      fabricating complexity.

PMID- 30278721
TI  - Cylindrical hot refractory anode vacuum arc (CHRAVA).
AB  - We present a study of a novel vacuum arc deposition system composed of a water
      cooled aluminum cathode and a hot refractory anode. The plasma of the arc system
      was diagnosed using a cylindrical electrostatic probe. It was found that the mean
      electron temperature was ~2 eV, the plasma density could be varied in the range
      of 0.5-6 * 1016 m-3, and the ion flux was between 0.06 and 0.35 A m-2. Optical
      emission spectroscopy measurements showed the presence of emission lines
      corresponding to Al i and Al ii. The characterization of the coatings showed that
      the deposition rate varied from 0.8 to 4 nm/s and the surface roughness (Ra) of
      the films was as low as 25 nm. We demonstrated that it was possible to deposit
      films with low macroparticle densities, overcoming the principal disadvantage of
      the vacuum arc process. Measurements of the arc voltage and current were
      performed as a function of time and the applied magnetic field. The anode
      temperature was measured using a pyrometer through a ZnS window as a function of
      time and arc current, and the maximum value was 1800  degrees C with heating
      rates of up to 110  degrees C/s.

PMID- 30278722
TI  - Elliptically bent crystal x-ray spectrometer for time-resolved laser plasma
      experiments.
AB  - Measuring time-resolved spectra is crucial in inertial confinement fusion and
      radiation source development experiments. An elliptically bent crystal
      spectrometer is designed to measure X-rays in the range of 2.5-11.0 keV, which
      was achieved using four different lattice spacings of 0.8512, 0.6687, 0.4246, and
      0.2749 nm with spectral resolution E/deltaE of ~500. The X-rays emitted from a
      source at one focus of the ellipse undergo Bragg reflection off a crystal and
      pass through the second focus of the ellipse to a streak camera slit with 18-mm
      length and 80-MUm width to generate a time-resolved spectrum. An alignment method
      for the time-resolved spectrometer was developed with the straight line
      connecting the centers of the two small holes on the fabricated substrate being
      the axis of the ellipse, thus allowing the spacing between the source and the
      elliptical crystal to be tuned to couple with the streak camera. The time
      resolved spectrometer's performance was experimentally tested at the Shenguang II
      laser facility. The results indicate that its performance is close to that
      predicted theoretically.

PMID- 30278723
TI  - Measurements of electron density profile by frequency modulated continuous wave
      reflectometer in the T-10 tokamak using high magnetic field side probing and
      extraordinary mode lower cutoff.
AB  - A new, previously unused combination of the high magnetic field side probing and
      the lower extraordinary mode cutoff was used in the T-10 tokamak for the electron
      density profile measurements by using a frequency modulation continuous wave
      reflectometer. This scheme has a significant advantage for large fusion machines
      where flat electron density profiles and high electron temperatures are expected.
      The reflectometer design is based on a common scheme with voltage controlled
      oscillators, active multipliers, and in-phase/quadrature signal detection.
      Iterative procedures were applied to calibrate a microwave source frequency and
      compensate the dispersion of probing signals in the conventional rectangular
      waveguides used as the transmission lines. About 0.2% stability of the beating
      frequency was reached after the calibration procedure had been finished. An
      advanced finite-difference scheme was proposed for the reconstruction of the
      electron density profile to reduce errors and improve the overall performance of
      the algorithm. Reconstructed electron density profiles demonstrate good agreement
      with conventional T-10 diagnostic data. Some specific technical and physical
      aspects of the diagnostic were also discussed on the basis of T-10 operation
      experience.

PMID- 30278724
TI  - Broadband loop gap resonator for nitrogen vacancy centers in diamond.
AB  - We present an S-band tunable loop gap resonator (LGR), which provides strong,
      homogeneous, and directionally uniform broadband microwave (MW) drive for
      nitrogen-vacancy (NV) ensembles. With 42 dBm of input power, the composite device
      provides drive field amplitudes approaching 5 G over a circular area ?50 mm2 or
      cylindrical volume ?250 mm3. The wide 80 MHz device bandwidth allows driving all
      NV Zeeman resonances for bias magnetic fields below 20 G. The device realizes
      percent-scale MW drive inhomogeneity; we measure a fractional root-mean-square
      inhomogeneity sigma rms = 1.6% and a peak-to-peak variation sigma pp = 3% over a
      circular area of 11 mm2 and sigma rms = 3.2% and sigma pp = 10.5% over a larger
      32 mm2 circular area. We demonstrate incident MW power coupling to the LGR using
      two methodologies: a printed circuit board-fabricated exciter antenna for
      deployed compact bulk sensors and an inductive coupling coil suitable for
      microscope-style imaging. The inductive coupling coil allows for approximately
      2pi steradian combined optical access above and below the device, ideal for
      envisioned and existing NV imaging and bulk sensing applications.

PMID- 30278725
TI  - Static and dynamic calibration of torsional spring constants of cantilevers.
AB  - A method for calibrating the dynamic torsional spring constant of cantilevers by
      directly measuring the thermally driven motion of the cantilever with an
      interferometer is presented. Random errors in calibration were made negligible
      (<1%) by averaging over multiple measurements. The errors in accuracy of +/-5% or
      +/-10% for both of the cantilevers calibrated in this study were limited only by
      the accuracy of the laser Doppler vibrometer (LDV) used to measure thermal
      fluctuations. This is a significant improvement over commonly used methods that
      result in large and untraceable errors resulting from assumptions made about the
      cantilever geometry, material properties, and/or hydrodynamic physics of the
      surroundings. Subsequently, the static torsional spring constant is determined
      from its dynamic counterpart after careful LDV measurements of the torsional mode
      shape, backed by finite element analysis simulations. A meticulously calibrated
      cantilever is used in a friction force microscopy experiment that measures the
      friction difference and interfacial shear strength (ISS) between graphene and a
      silicon dioxide AFM probe. Accurate calibration can resolve discrepancies between
      different experimental methods, which have contributed to a large scatter in the
      reported friction and ISS values in the literature to date.

PMID- 30278726
TI  - An open and flexible digital phase-locked loop for optical metrology.
AB  - This paper presents an open and flexible digital phase-locked loop optimized for
      laser stabilization systems. It is implemented on a cheap and easily accessible
      FPGA-based digital electronics platform (Red Pitaya) running a customizable open
      source firmware. A PC-based software interface allows controlling the platform
      and optimizing the loop parameters remotely. Several tools are included to allow
      measurement of quantities of interest smoothly and rapidly. To demonstrate the
      platform's capabilities, we built a fiber noise canceller over a 400 m fiber
      link. Noise cancellation was achieved over a 30 kHz bandwidth, a value limited
      mainly by the delays introduced by the actuator and by the round-trip propagation
      over the fiber link. We measured a total latency of 565 ns for the platform
      itself, limiting the theoretically achievable control bandwidth to approximately
      225 kHz.

PMID- 30278727
TI  - Multiplexed characterization of complex gas-phase mixtures combining chirped
      pulse Fourier transform microwave spectroscopy and VUV photoionization time-of
      flight mass spectrometry.
AB  - We report details of the design and operation of a single apparatus that combines
      Chirped-Pulse Fourier Transform Microwave (CP-FTMW) spectroscopy with vacuum
      ultraviolet (VUV) photoionization Time-of-Flight Mass Spectrometry (TOFMS). The
      supersonic expansion used for cooling samples is interrogated first by passing
      through the region between two microwave horns capable of broadband excitation
      and detection in the 2-18 GHz frequency region of the microwave. After passing
      through this region, the expansion is skimmed to form a molecular beam, before
      being probed with 118 nm (10.5 eV) single-photon VUV photoionization in a linear
      time-of-flight mass spectrometer. The two detection schemes are powerfully
      complementary to one another. CP-FTMW detects all components with significant
      permanent dipole moments. Rotational transitions provide high-resolution
      structural data. VUV TOFMS provides a gentle and general method for ionizing all
      components of a gas phase mixture with ionization thresholds below 10.5 eV,
      providing their molecular formulae. The advantages, complementarity, and
      limitations of the combined methods are illustrated through results on two gas
      phase mixtures made up of (i) three furanic compounds, two of which are
      structural isomers of one another, and (ii) the effluent from a flash pyrolysis
      source with o-guaiacol as the precursor.

PMID- 30278728
TI  - Next-generation diamond cell and applications to single-crystal neutron
      diffraction.
AB  - A diamond cell optimized for single-crystal neutron diffraction is described. It
      is adapted for work at several of the single-crystal diffractometers of the
      Spallation Neutron Source and the High Flux Isotope Reactor at the Oak Ridge
      National Laboratory (ORNL). A simple spring design improves portability across
      the facilities and affords load maintenance from offline pressurization and
      during temperature cycling. Compared to earlier prototypes, pressure stability of
      polycrystalline diamond (Versimax(r)) has been increased through double-conical
      designs and ease of use has been improved through changes to seat and piston
      setups. These anvils allow ~30%-40% taller samples than possible with comparable
      single-crystal anvils. Hydrostaticity and the important absence of shear pressure
      gradients have been established with the use of glycerin as a pressure medium.
      Large single-crystal synthetic diamonds have also been used for the first time
      with such a clamp-diamond anvil cell for pressures close to 20 GPa. The cell is
      made from a copper beryllium alloy and sized to fit into ORNL's magnets for
      future ultra-low temperature and high-field studies. We show examples from the
      Spallation Neutron Source's SNAP and CORELLI beamlines and the High Flux Isotope
      Reactor's HB-3A and IMAGINE beamlines.

PMID- 30278729
TI  - The phosphor temperature measurement of white light-emitting diodes based on
      magnetic nanoparticle thermometer.
AB  - There is much debate about whether the junction temperature or phosphor
      temperature is higher in white light-emitting diodes (LEDs). The main reason is
      that the junction and phosphor temperatures cannot be measured directly using
      traditional temperature measurement tools. In this study, a magnetic nanoparticle
      thermometer, a nondestructive and precise temperature measurement tool, is
      introduced and described in detail. The model, measurement principle, and
      experimental setup are described. The temperature of the phosphor layer and the
      top surface of the P-N junction in white LEDs was measured directly using the
      magnetic nanoparticle thermometer, and the results show that the phosphor layer
      temperature was higher than the chip top surface temperature at different input
      voltages, providing a reference for relative researchers.

PMID- 30278730
TI  - Signal-to-noise ratio analysis and improvement for fluorescence tomography
      imaging.
AB  - CCD-based fluorescence tomography is widely used for small animal whole-body
      imaging. In this report, systematic signal-to-noise ratio (SNR) analyses of a
      fluorescence tomography imaging (FTI) system were performed, resulting in an easy
      to-follow strategy to optimize hardware configurations and operational conditions
      for acquiring high-quality imaging data and for improving the overall system
      performance. Phantom experiments were conducted to demonstrate the performance
      improvement by these optimizations. The improved performance was further verified
      by imaging a tumor-bearing mouse in vivo. This report provides general and
      practical guidelines for setting up a high-performance electron multiplying
      charge coupled device based FTI system to achieve an optimized SNR, which can be
      useful for future FTI technology development.

PMID- 30278731
TI  - Metrological large range magnetic force microscopy.
AB  - A new metrological large range magnetic force microscope (Met. LR-MFM) has been
      developed. In its design, the scanner motion is measured by using three laser
      interferometers along the x, y, and z axes. Thus, the scanner position and the
      lift height of the MFM can be accurately and traceably determined with
      subnanometer accuracy, allowing accurate and traceable MFM measurements. The Met.
      LR-MFM has a measurement range of 25 mm * 25 mm * 5 mm, larger than conventional
      MFMs by almost three orders of magnitude. It is capable of measuring samples from
      the nanoscale to the macroscale, and thus, it has the potential to bridge
      different magnetic field measurement tools having different spatially resolved
      scales. Three different measurement strategies referred to as Topo&MFM, MFMXY,
      and MFMZ have been developed. The Topo&MFM is designed for measuring topography
      and MFM phase images, similar to conventional MFMs. The MFMXY differs from the
      Topo&MFM as it does not measure the topography profile of surfaces at the second
      and successive lines, thus reducing tip wear and saving measurement time. The
      MFMZ allows the imaging of the stray field in the xz- or yz-planes. A number of
      measurement examples on a multilayered thin film reference sample made of [Co(0.4
      nm)/Pt(0.9 nm)]100 and on a patterned magnetic multilayer [Co(0.4 nm)/Pt(0.9
      nm)]10 with stripes with a 9.9 MUm line width and 20 MUm periodicity are
      demonstrated, indicating excellent measurement performance.

PMID- 30278732
TI  - Current capabilities of the residual stress diffractometer at the high flux
      isotope reactor.
AB  - The engineering diffractometer 2nd Generation Neutron Residual Stress Facility
      (NRSF2) at the Oak Ridge National Laboratory's High Flux Isotope Reactor was
      built specifically for the mapping of residual strains. NRSF2 is optimized to
      investigate a wide range of engineering materials by providing the user a
      selection of monochromatic neutron wavelengths to maintain the selected Bragg
      reflection near 2theta = 90 degrees , which is the optimal scattering geometry
      for strain mapping. Details of the instrument configuration and operation are
      presented, and considerations for experimental planning are also discussed.
      Selected examples of recent residual stress work completed with NRSF2 are
      presented to highlight capabilities.

PMID- 30278733
TI  - Verification of Doppler coherence imaging for 2D ion velocity measurements on
      DIII-D.
AB  - Coherence Imaging Spectroscopy (CIS) has emerged as a powerful tool for
      investigating complex ion phenomena in the boundary of magnetically confined
      plasma devices. The combination of Fourier-transform interferometry and high
      resolution fast-framing cameras has made it possible to make sensitive velocity
      measurements that are also spatially resolved. However, this sensitivity makes
      the diagnostic vulnerable to environmental effects including thermal drifts,
      vibration, and magnetic fields that can influence the velocity measurement.
      Additionally, the ability to provide an absolute calibration for these geometries
      can be impacted by differences in the light-collection geometry between the
      plasma and reference light source, spectral impurities, and the presence of thin
      films on in-vessel optics. This paper discusses the mitigation of these effects
      and demonstration that environmental effects result in less than 0.5 km/s error
      on the DIII-D CIS systems. A diagnostic comparison is used to demonstrate
      agreement between CIS and traditional spectroscopy once tomographic artifacts are
      accounted for.

PMID- 30278734
TI  - Atomic scale shot-noise using cryogenic MHz circuitry.
AB  - By implementing dedicated cryogenic circuitry operating in the MHz regime, we
      have developed a scanning tunneling microscope (STM) capable of conventional, low
      frequency (<10 kHz), microscopy as well spectroscopy and shot-noise detection at
      1 MHz. After calibrating our AC circuit on a gold surface, we illustrate our
      capability to detect shot-noise at the atomic scale and at low currents (<1 nA)
      by simultaneously measuring the atomically resolved differential conductance and
      shot-noise on the high temperature superconductor Bi2Sr2CaCu2O8+x . We further
      show our direct sensitivity to the temperature of the tunneling electrons at low
      voltages. Our MHz circuitry opens up the possibility to study charge and
      correlation effects at the atomic scale in all materials accessible to STM.

PMID- 30278735
TI  - A laser scanning microscope executing intraframe polarization switching of the
      illumination beam.
AB  - The polarization of the illumination beam in a beam scanning microscope such as
      the confocal microscope plays an important role in extracting the orientational
      information of the molecules in the specimen. In this paper, we present the
      development of a beam scanning microscope comprising a custom designed optical
      arrangement to obtain images of the same target with different polarizations of
      the illumination beam. The optical arrangement, based on a ferroelectric liquid
      crystal spatial light modulator (FELCSLM), can generate homogeneous as well as
      non-homogeneous user defined polarization profiles over the cross-sectional area
      of the illumination beam. Here, we employ a computer generated holography
      technique and exploit the programmability of the FELCSLM display to considerably
      reduce the time gap between two successive illuminations of each location of the
      specimen with two different polarizations. We demonstrate the working of the beam
      scanning microscope where the polarization profile of the illumination beam is
      switched at the end of every line scanned, in contrast to a conventional beam
      scanning microscope where the polarization can be switched at the end of every
      frame scanned. Preliminary experimental results obtained using a polarization
      sensitive target confirm the feasibility of the proposed scheme.

PMID- 30278736
TI  - Note: Simultaneous modulation transfer spectroscopy on transitions of multiple
      atomic species for compact laser frequency reference modules.
AB  - We present a technique for simultaneous laser frequency stabilization on
      transitions of multiple atomic species with a single optical setup. The method is
      based on modulation transfer spectroscopy, and the signals are separated by
      modulating at different frequencies and electronically filtered. As a proof of
      concept, we demonstrate simultaneous spectroscopy of the potassium D1, D2 and
      rubidium D2 transitions. The technique can be extended in principle to other
      atomic species given the availability of optics and cells and allows the
      development of versatile and compact frequency reference modules.

PMID- 30278737
TI  - A neutral wind instrument for nano-satellite platforms.
AB  - Here we describe the first neutral wind sensor developed specifically for use on
      resource limited nano-satellite platforms. The instrument is a next generation
      redesign of the ram wind sensor flown on the Communications/Navigation Outage
      Forecasting System satellite for measurements of neutral velocity, temperature,
      and composition. Results of subsystem tests in vacuum conditions show low-power
      operation, promising design, and good resolution of measured parameters over the
      operational pressure and energy ranges expected in the low Earth orbit
      environment.

PMID- 30278738
TI  - A plasma-triggered gas switch.
AB  - This paper presents a low-jitter, low-trigger-threshold, high-dielectric-constant
      ceramic, plasma-triggered gas switch developed for pulsed power generators. We
      also discuss the principles behind the switch and the experiments and numerical
      calculations used. The electron emission and surface flashover in the trigger
      structure are used to create the initial plasma for switch breakdown. The
      experimental results show that the switch is triggered stably with a negative
      pulse of -50 kV peak and has a breakdown delay time jitter of 2-3 ns. In this
      jitter performance, the switch has a switch coefficient below 20%, and a peak
      current-carrying ability of at least +/-5 kA in dry air at atmospheric pressure.
      The switch can also be reliably triggered with a switch coefficient of 49.7% and
      an over-voltage ratio of only 0.16 in dry air.

PMID- 30278739
TI  - Investigation of multifilament MgB2 superconducting joint technique for
      development of MRI magnets.
AB  - This study presents the investigation of superconducting joints fabricated using
      multifilament magnesium diboride (MgB2) wires for the development of persistent
      current mode magnetic resonance imaging (MRI) magnets. The critical current of
      the jointed samples decreased with increasing cutting angle because the smaller
      cutting angle allowed greater exposure of the MgB2 filament, thereby increasing
      the contact area for the wire-bulk-wire connection. In addition, an appropriate
      pressing pressure (300 MPa) was necessary to establish the multifilament MgB2
      joint without significant degradation of superconducting properties. The
      resistance of the optimal MgB2 joint, measured using the field-decay technique,
      was <1.5 * 10-14 Omega. Therefore, the proposed joint technique can be employed
      for developing multifilament MgB2 MRI magnets operating in the persistent-current
      mode.

PMID- 30278740
TI  - Investigation of comb-type pulse forming line with low impedance.
AB  - Development of pulsed power technology is toward higher power, longer duration,
      and more compact structures. Compact coaxial propylene carbonate pulse forming
      lines are widely used in the application of pulsed power systems. In order to
      further lengthen the duration and decrease the geometrical sizes of pulsed power
      systems, a comb-type pulse forming line is adopted. It is a slow-wave structure
      with a comb-type inner electrode. In this paper, the operation principle,
      theoretical analysis, numerical simulation, and experimental investigation of the
      comb-type forming line are carried out, respectively. First, the operation
      principle is briefly introduced. The principle to increase the duration is
      explained. Second, the theoretical analyses about the dispersion relation are
      proposed. Third, the PSpice model is built by the L-C network. Based on the
      calculated parameters, the electrical circuit is simulated. A Computer Simulation
      Technology (CST) model is also built, which allows for a straightforward coupling
      of electric and magnetic (EM) simulation and circuit simulation. Finally, the
      comb-type pulse forming line is experimentally tested and verified. For the comb
      type propylene carbonate forming line with a 67 cm length to replace the
      traditional coaxial one, it has an impedance of 8 Omega and a duration of 64 ns.
      Experimental data on its test results are given. The experimental results are in
      accordance with the numerical simulations. The investigation approved the comb
      type pulse forming line feasible and set a solid foundation for its application
      in the pulsed power system.

PMID- 30278741
TI  - Cryo scanning transmission x-ray microscope optimized for spectrotomography.
AB  - A cryo scanning transmission X-ray microscope, the cryo-STXM, has been designed
      and commissioned at the Canadian Light Source synchrotron. The instrument is
      designed to operate from 100 to 4000 eV (lambda = 12.4 - 0.31 nm). Users can
      insert a previously frozen sample, through a load lock, and rotate it +/-70
      degrees  in the beam to collect tomographic data sets. The sample can be
      maintained for extended periods at 92 K primarily to suppress radiation damage
      and a pressure on the order of 10-9 Torr to suppress sample contamination. The
      achieved spatial resolution (30 nm) and spectral resolution (0.1 eV) are similar
      to other current soft X-ray STXMs, as demonstrated by measurements on known
      samples and test patterns. The data acquisition efficiency is significantly more
      favorable for both imaging and tomography. 2D images, 3D tomograms, and 4D
      chemical maps of automotive hydrogen fuel cell thin sections are presented to
      demonstrate current performance and new capabilities, namely, cryo
      spectrotomography in the soft X-ray region.

PMID- 30278742
TI  - Record indoor magnetic field of 1200 T generated by electromagnetic flux
      compression.
AB  - A peak field of 1200 T was generated by the electromagnetic flux-compression
      (EMFC) technique with a newly developed megagauss generator system. Magnetic
      fields closely up to the turn-around peak were recorded by a reflection-type
      Faraday rotation magnetic-field optical-fiber probe. The performance was analyzed
      and compared with data obtained by the preceding EMFC experiments to show a
      significant increase in the liner imploding speed of up to 5 km/s.

PMID- 30278743
TI  - Extending the limits of powder diffraction analysis: Diffraction parameter space,
      occupancy defects, and atomic form factors.
AB  - Although the determination of site occupancies is often a major goal in Rietveld
      refinement studies, the accurate refinement of site occupancies is exceptionally
      challenging due to many correlations and systematic errors that have a hidden
      impact on the final refined occupancy parameters. Through the comparison of
      results independently obtained from neutron and synchrotron powder diffraction,
      improved approaches capable of detecting occupancy defects with an exceptional
      sensitivity of 0.1% (absolute) in the class of layered NMC (Li[NixMnyCoz]O2) Li
      ion battery cathode materials have been developed. A new method of visualizing
      the diffraction parameter space associated with crystallographic site scattering
      power through the use of f* diagrams is described, and this method is broadly
      applicable to ternary compounds. The f* diagrams allow the global minimum fit to
      be easily identified and also permit a robust determination of the number and
      types of occupancy defects within a structure. Through a comparison of neutron
      and X-ray diffraction results, a systematic error in the synchrotron results was
      identified using f* diagrams for a series of NMC compounds. Using neutron
      diffraction data as a reference, this error was shown to specifically result from
      problems associated with the neutral oxygen X-ray atomic form factor and could be
      eliminated by using the ionic O2- form factor for this anion while retaining the
      neutral form factors for cationic species. The f* diagram method offers a new
      opportunity to experimentally assess the quality of atomic form factors through
      powder diffraction studies on chemically related multi-component compounds.

PMID- 30278744
TI  - Advances in utilizing event based data structures for neutron scattering
      experiments.
AB  - This article strives to expand on existing work to demonstrate advancements in
      data processing made available using event mode measurements. Most spallation
      neutron sources in the world have data acquisition systems that provide event
      recording. The new science that is enabled by utilizing event mode has only begun
      to be explored. In the past, these studies were difficult to perform because
      histograms forced dealing with either large chunks of time or a large number of
      files. With event based data collection, data can be explored and rebinned long
      after the measurement has completed. This article will review some of the
      principles of event data and how the method opens up new possibilities for in
      situ measurements, highlighting techniques that can be used to explore changes in
      the data. We also demonstrate the statistical basis for determining data quality
      and address the challenge of determining how long to measure mid-measurement.
      Finally, we demonstrate a model independent method of grouping data via
      hierarchical clustering methods that can be used to improve calibration,
      reduction, and data exploration.

PMID- 30278745
TI  - Note: A Laue crystal imager for high energy quasi-monochromatic x-ray.
AB  - A newly designed transmission type x-ray Laue imager for tens of keV hard x-rays
      is reported. Compared with the traditional reflection type x-ray crystal imager,
      the transmission geometry produces a much better image quality for high energy
      hard x-rays. This system was assessed via a calibration experiment performed at
      the SPring8 synchrotron radiation facility. With a Ta x-ray fluorescer, the mono
      energetic x-ray at 70 keV from the synchrotron radiation was converted to an
      isotropically emitted Ta K-shell source at 57.5 keV and 65 keV. A tungsten
      pinhole array was employed as the test object, and clear images of the pinholes
      with a magnification of ~5 were acquired. These images exhibited superior quality
      in the dispersion plane. As an extension of this work, a slit-free full-spectral
      Laue imager is proposed for high resolution hard x-ray imaging.

PMID- 30278746
TI  - The high pressure gas capabilities at Oak Ridge National Laboratory's neutron
      facilities.
AB  - The study of samples subjected to high pressure gas is an important asset in
      materials research and has consequently been a priority of the sample environment
      development at the Oak Ridge National Laboratory's (ORNL) neutron program. Such
      effort has resulted in the availability of an extensive combination of pressure
      cells and gas intensifiers (both commercially available and custom made). These
      resources are available across both neutron facilities at ORNL: the Spallation
      Neutron Source and the High Flux Isotope Reactor. Current capabilities include,
      for example, in situ measurements up to 6 kbar and a 3 kbar hydrogen-capable
      intensifier with a gas recovery feature. In this communication, we will review
      the existing suite of high pressure gas capabilities, with special emphasis on
      recent in-house developments. A number of examples will be presented to
      illustrate how such capabilities are being deployed on neutron beamlines to
      enable frontier science.

PMID- 30278747
TI  - Erratum: "Note: Multi-gap gas switch with low trigger-threshold voltage by
      mounting resistors and capacitors in parallel with switch gaps" [Rev. Sci.
      Instrum. 89, 096105 (2018)].

PMID- 30278748
TI  - Transient process based electromagnetic flow measurement methods and
      implementation.
AB  - The ordinary electromagnetic flowmeter (EMF) utilizes the steady-state period of
      the excitation current for measuring the flow rate in order to ensure zero
      stability and measurement accuracy. In this paper, the transient process of EMF
      is studied to measure the flow rate so as to realize applications requiring ultra
      low power consumption, for example, water meters. For this reason, the dynamic
      excitation current and signal voltage of the transient process are analyzed, and
      three kinds of transient measurement methods are proposed to determine the
      relationship between the processing results of the signal voltage and flow rates.
      They are the voltage-current ratio method, voltage-current differential method,
      and differential interference compensation method. In order to verify these
      measurement methods, a DSP (Digital Signal Processor) that is the same processing
      chip as the current ordinary electromagnetic flow transmitter is selected to
      design a hardware system of the transmitter, and the excitation current and
      signal voltage of the transient process are acquired. Analysis of experimental
      data shows that there is a good linear relationship between the processing
      results of the signal voltage and flow rates. The software of the electromagnetic
      flow transmitter based on DSP is developed, and the transient measurement methods
      are realized in real time so as to perform the water flow calibration experiments
      and power consumption tests. The experimental results show that the measurement
      accuracy is 0.5% which is the same as the ordinary EMF. Comparisons of power
      consumption show that the excitation power consumption of EMF based on the
      transient measurement principle is 1/1200 of that of the ordinary EMF.

PMID- 30278750
TI  - Adaptation of a visible wavelength fluorescence microplate reader for discovery
      of near-infrared fluorescent probes.
AB  - We present an inexpensive, generalizable approach for modifying visible
      wavelength fluorescence microplate readers to detect emission in the near
      infrared (NIR) I (650-950 nm) and NIR II (1000-1350 nm) tissue imaging windows.
      These wavelength ranges are promising for high sensitivity fluorescence-based
      cell assays and biological imaging, but the inaccessibility of NIR microplate
      readers is limiting development of the requisite, biocompatible fluorescent
      probes. Our modifications enable rapid screening of NIR candidate probes, using
      short pulses of UV light to provide excitation of diverse systems including dye
      molecules, semiconductor quantum dots, and metal clusters. To confirm the utility
      of our approach for rapid discovery of new NIR probes, we examine the silver
      cluster synthesis products formed on 375 candidate DNA strands that were
      originally designed to produce green-emitting, DNA-stabilized silver clusters.
      The fast, sensitive system developed here discovered DNA strands that
      unexpectedly stabilize NIR-emitting silver clusters.

PMID- 30278751
TI  - A novel lightweight TE01-TE20 mode converter with broad bandwidth and aligned
      ports.
AB  - A novel TE01-TE20 mode converter is designed and fabricated by 3-D printing in
      this paper. It can realize high-efficiency (>97.5%) mode conversion in broadband
      from 27 to 40 GHz. Its weight is 0.011 kg only, and its coupling cavity
      normalized length is 0.39lambda. An out-of-phase power divider is designed to
      verify the mode converter by observing the difference of output phase and flat
      frequency characteristics when connected to the mode converter. A sample
      converter with a power divider was then tested. Flat frequency characteristics
      for power dividing and anti-phase outputs are obtained in the working bandwidth
      to verify the mode converter with a good performance of mode conversion.

PMID- 30278752
TI  - New software protocols for enabling laboratory based temporal CT.
AB  - Temporal micro-computed tomography (CT) allows the non-destructive quantification
      of processes that are evolving over time in 3D. Despite the increasing popularity
      of temporal CT, the practical implementation and optimisation can be difficult.
      Here, we present new software protocols that enable temporal CT using commercial
      laboratory CT systems. The first protocol drastically reduces the need for
      periodic intervention when making time-lapse experiments, allowing a large number
      of tomograms to be collected automatically. The automated scanning at regular
      intervals needed for uninterrupted time-lapse CT is demonstrated by analysing the
      germination of a mung bean (vigna radiata), whilst the synchronisation with an in
      situ rig required for interrupted time-lapse CT is highlighted using a shear cell
      to observe granular segregation. The second protocol uses golden-ratio angular
      sampling with an iterative reconstruction scheme and allows the number of
      projections in a reconstruction to be changed as sample evolution occurs. This
      overcomes the limitation of the need to know a priori what the best time window
      for each scan is. The protocol is evaluated by studying barite precipitation
      within a porous column, allowing a comparison of spatial and temporal resolution
      of reconstructions with different numbers of projections. Both of the protocols
      presented here have great potential for wider application, including, but not
      limited to, in situ mechanical testing, following battery degradation and
      chemical reactions.

PMID- 30278753
TI  - Note: Thermal conductivity measurement of individual porous polyimide fibers
      using a modified wire-shape 3omega method.
AB  - Porous polyimide fiber enjoys a good reputation as a high temperature resistant
      thermal insulation material in an aircraft-carrier, a spacecraft, and other
      military sophisticated products. Understanding its thermal conductivity is
      especially important for the design optimization and thermal management in these
      applications. In this study, a modified wire-shape 3omega method is developed to
      measure the thermal conductivity of individual porous polyimide fibers, utilizing
      a platinum layer heater/thermometer deposited along the circumferential direction
      of the fiber. The new method is first validated using a platinum wire with known
      thermophysical properties such as thermal conductivity at room temperature and
      then applied to porous polyimide fibers with diverse porosities. The thermal
      conductivity of porous polyimide fibers at room temperature is 0.06-0.15 W m-1 K
      1, which reflects a good thermal insulation performance.

PMID- 30278754
TI  - Time filtering of event based neutron scattering data: A pathway to study the
      dynamic structural responses of materials.
AB  - Time-resolved diffraction has become a vital tool for probing dynamic responses
      to an applied stimulus. Such experiments traditionally use hardware solutions to
      histogram measured data into their respective bin. We will show that a major
      advantage of event-based data acquisition, which time-stamps measured diffraction
      data with 100 ns accuracy, is much preferred over hardware histogramming of the
      data by enabling postprocessing for advanced custom binning using a software
      solution. This approach is made even more powerful by coupling measured
      diffraction data with metadata about the applied stimuli and material response.
      In this work, we present a time-filter approach that leverages the power of event
      based diffraction collection to reduce stroboscopic data measured over many hours
      into equally weighted segments that represent subsets of the response to a single
      cycle of the applied stimulus. We demonstrate this approach by observing
      ferroelectric/ferroelastic domain wall motion during electric field cycling of
      BaTiO3. The developed approach can readily be expanded to investigate other
      dynamic phenomena using complex sample environments.

PMID- 30278755
TI  - A uniaxial load frame for in situ neutron studies of stress-induced changes in
      cementitious materials and related systems.
AB  - For in situ neutron scattering experiments on cementitious materials, it is of
      great interest to have access to a robust device which can induce uniaxial load
      on a given solid sample. Challenges involve selection of materials making up the
      apparatus that are both weak neutron scatterers and yet adequately strong to
      induce loads of up to a few kilonewtons on the sample. Here, the design and
      experimental commissioning of a novel load frame is provided with the intended
      use as a neutron scattering sample environment enabling time-dependent stress
      induced changes to be probed in an engineering material under compression. The
      frame is a scaled down version of a creep apparatus, which is typically used in
      the laboratory to measure deformation due to creep in concrete. Components were
      optimized to enable 22 MPa of compressive stress to be exerted on a 1 cm diameter
      cement cylinder. To minimize secondary scattering signals from the load frame,
      careful selection of the metal components was needed. Furthermore, due to the
      need to maximize the wide angular detector coverage and signal to noise for
      neutron total scattering measurements, the frame was designed specifically to
      minimize the size and required number of support posts while matching sample
      dimensions to the available neutron beam size.

PMID- 30278757
TI  - Dual energy-band excitation from a low power Rh anode X-ray tube for the
      simultaneous determination of low Z and high Z elements (Na-U) using total
      reflection X-ray fluorescence analysis (TXRF).
AB  - This article presents results from an experimental setup for a dual energy-band
      vacuum spectrometer for total-reflection X-ray fluorescence analysis allowing
      simultaneous efficient excitation of low, medium, and high Z elements. The
      spectrometer is equipped with an air-cooled 35 W low power Rh X-ray tube and a 17
      mm2 silicon drift detector with a thin 8 um beryllium window. A Pd/B4C multilayer
      monochromator is used at the same time as a Bragg reflector for Rh-Kalpha
      radiation and as a high-energy cut-off reflector above 5 keV, where the
      characteristic Rh-L radiation is totally reflected and present in the spectrum of
      the exciting radiation. This leaves one broad low energy band below 5 keV and one
      high energy band around the energy of Rh-Kalpha. As Rh-L radiation would be
      absorbed on its path through air, a new beam entrance system was designed in
      order to guide the Rh-L photons into the vacuum chamber for efficient excitation
      of low Z elements. With this setup, elements down to sodium (Z = 11, E = 1.04
      keV) could be detected. First results are presented, and spectra obtained in air
      as well as in vacuum are compared and discussed. Detection limits in the range of
      1000 ug/kg for Na and around 140 ug/kg for Mg were achieved using the NIST SRM
      1640 (trace elements in water).

PMID- 30278756
TI  - Note: Multi-gap gas switch with low trigger-threshold voltage by mounting
      resistors and capacitors in parallel with switch gaps.
AB  - To reduce the trigger threshold voltage of the multi-gap gas switch used for
      linear transformer drivers, a method is proposed by mounting resistors and
      capacitors in parallel with the switch gaps. Based on the circuit model of the
      six-gap gas switch, the gap voltage distribution during the triggering process is
      analyzed. When the multi-gap gas switch is triggered, the voltage distribution
      between gaps is mainly determined by the stray capacitance between electrodes. In
      such condition, the trigger voltage is not fully applied on the trigger gap, and
      as a consequence, a higher trigger voltage is required for obtaining a low
      jitter. The effects of capacitor parameters on the triggering characteristics of
      the switch are experimentally investigated. Compared with the original switch
      design, the results indicate that at a charging voltage of +/-80 kV and operating
      at 60% of the self-breakdown voltage, the trigger voltage is reduced from 110 kV
      to 75 kV while the 3.2 ns jitter of the switch is preserved.

PMID- 30278758
TI  - Dynamically enhanced low-coherence interferometry.
AB  - In the investigations of inhomogeneous media, availability of methods to study
      the interior of the material without affecting it is valuable. Optical coherence
      tomography provides such a functionality by providing depth resolved images of
      semi-transparent objects non-invasively. This is especially useful in medicine
      and is used not only in research but also in clinical practice. Optical coherence
      tomography characterizes each cross section by its reflectance. The basic physics
      principle underlying optical coherence tomography is low-coherence
      interferometry, which is combined with lateral scanning to produce cross
      sections. It is clearly desirable to obtain more detailed information regarding
      each cross section, if available. We have developed a system which measures the
      fluctuation spectra at all depths in low-coherence interferometry. By providing
      more information for each cross section, this can in principle be effective in
      tissue characterization and pathological diagnosis. The system uses the time
      dependence of the low-coherence interferometry data to obtain the fluctuation
      spectrum at each depth. Additionally, noise reduction is applied to obtain the
      spectra without unwanted noise, such as shot-noise, which can swamp the signal.
      The measurement system is applied to samples with no external stimuli, and depth
      resolved thermal fluctuation spectra of the samples are obtained. These spectra
      are compared with their corresponding theoretical expectations and are found to
      agree. The measurement system requires dualizing the detectors in the low
      coherence interferometer but otherwise requires little additional equipment. The
      measurements were performed in ten to a hundred seconds.

PMID- 30278759
TI  - Broadband longwave radio remote sensing instrumentation.
AB  - We present the performance characteristics of a high-sensitivity radio receiver
      for the frequency band 0.5-470 kHz, known as the Low Frequency Atmospheric
      Weather Electromagnetic System for Observation, Modeling, and Education, or LF
      AWESOME. The receiver is an upgraded version of the VLF AWESOME, completed in
      2004, which provided high sensitivity broadband radio measurements of natural
      lightning emissions, transmitting beacons, and radio emissions from the near
      Earth space environment. It has been deployed at many locations worldwide and
      used as the basis for dozens of scientific studies. We present here a significant
      upgrade to the AWESOME, in which the frequency range has been extended to include
      the LF and part of the medium frequency (MF) bands, the sensitivity improved by
      10-25 dB to be as low as 0.03 fT/ Hz , depending on the frequency, and timing
      error reduced to 15-20 ns range. The expanded capabilities allow detection of
      radio atmospherics from lightning strokes at global distances and multiple
      traverses around the world. It also allows monitoring of transmitting beacons in
      the LF/MF band at thousands of km distance. We detail the specification of the LF
      AWESOME and demonstrate a number of scientific applications. We also describe and
      characterize a new algorithm for minimum shift keying demodulation for VLF/LF
      transmitters for ionospheric remote sensing applications.

PMID- 30278760
TI  - A scanning tunneling microscope for spectroscopic imaging below 90 mK in magnetic
      fields up to 17.5 T.
AB  - We describe the development and performance of an ultra-high vacuum scanning
      tunneling microscope working under combined extreme conditions of ultra-low
      temperatures and high magnetic fields. We combined a top-loading dilution
      refrigerator and a standard bucket dewar with a bottom-loading superconducting
      magnet to achieve 4.5 days operating time, which is long enough to perform
      various spectroscopic-imaging measurements. To bring the effective electron
      temperature closer to the mixing-chamber temperature, we paid particular
      attention to filtering out radio-frequency noise, as well as enhancing the
      thermal link between the microscope unit and the mixing chamber. We estimated the
      lowest effective electron temperature to be below 90 mK by measuring the
      superconducting-gap spectrum of aluminum. We confirmed the long-term stability of
      the spectroscopic-imaging measurement by visualizing superconducting vortices in
      the cuprate superconductor Bi2Sr2CaCu2O8+delta .

PMID- 30278761
TI  - FRAC: Fringing-RF-field-activated dc-to-pulse converter for low-energy ion beams.
AB  - We developed a new type of dc-to-pulse converter, called FRAC (Fringing-RF-field
      Activated dc-to-pulse Converter) for low-energy ion beams electrostatically
      accelerated from an ion source. FRAC is based on a radio-frequency quadrupole
      (RFQ) linear trap technique and works in principle under ultrahigh vacuum
      conditions. Ions continuously injected into FRAC are decelerated by an
      alternating longitudinal electric field produced in a distorted radio frequency
      field around the edge region of RFQ rods. These ions accumulate in FRAC for a
      significantly long time. This edge effect appears most notably when the energy of
      incoming ions exceeds the injection barrier potential by less than a few eV and
      the energy spread is quite small. The ions stacked during the FRAC operation
      period are ejected as a high intensity pulsed beam. We investigated the
      performance of FRAC and the capability of some FRAC operation methods developed
      to enhance the dc-to-pulse conversion efficiency. The maximum conversion
      efficiencies achieved were 22% and 5.6% at FRAC operation frequencies of 10 and 1
      Hz, respectively. The number of ions contained in an output beam pulse with a
      duration of 500 MUs was in practice 1.6 * 109 ions/pulse at an injected dc beam
      intensity of 4.6 nA and an operation frequency of 1 Hz.

PMID- 30278762
TI  - Diagnostic capacity of electron cyclotron emission imaging system with continuous
      large observation area on EAST tokamak.
AB  - Electron cyclotron emission imaging on EAST provides direct measurements of the 2
      D electron temperature dynamics in a continuous large observation area with high
      temporal and spatial resolution. Besides the normal MHD investigation, a system
      with a view field large enough to cover the core plasma region has been applied
      to extract more plasma information, such as the plasma center location, the
      deposition location of auxiliary heating, and the core toroidal rotation speed.
      These results solely based on electron cyclotron emission imaging (ECEI) data are
      consistent with the results of the equilibrium fitting (EFIT), numerical code,
      and other diagnostics, which indicate the powerful diagnostic capacity of this
      ECEI system.

PMID- 30278763
TI  - Fabrication of a precise ellipsoidal mirror for soft X-ray nanofocusing.
AB  - In X-ray focusing, grazing incidence mirrors offer advantages of no chromatic
      aberration and high focusing efficiency. Although nanofocusing mirrors have been
      developed for the hard X-ray region, there is no mirror with nanofocusing
      performance in the soft X-ray region. Designing a system with the ability to
      focus to a beam size smaller than 100 nm at an X-ray energy of less than 1 keV
      requires a numerical aperture larger than 0.01. This leads to difficulties in the
      fabrication of a soft X-ray focusing mirror with high accuracy. Ellipsoidal
      mirrors enable soft X-ray focusing with a high numerical aperture. In this study,
      we report a production process for ellipsoidal mirrors involving mandrel
      fabrication and replication processes. The fabricated ellipsoidal mirror was
      assessed under partial illumination conditions at the soft X-ray beamline
      (BL25SU) of SPring-8. A focal spot size of less than 250 nm was confirmed at 300
      eV. The focusing tests indicated that the proposed fabrication process is
      promising for X-ray mirrors that have the form of a solid of revolution,
      including Wolter mirrors.

PMID- 30278764
TI  - A new elliptical-beam method based on time-domain thermoreflectance (TDTR) to
      measure the in-plane anisotropic thermal conductivity and its comparison with the
      beam-offset method.
AB  - Materials lacking in-plane symmetry are ubiquitous in a wide range of
      applications such as electronics, thermoelectrics, and high-temperature
      superconductors, in all of which the thermal properties of the materials play a
      critical part. However, very few experimental techniques can be used to measure
      in-plane anisotropic thermal conductivity. A beam-offset method based on time
      domain thermoreflectance (TDTR) was previously proposed to measure in-plane
      anisotropic thermal conductivity. However, a detailed analysis of the beam-offset
      method is still lacking. Our analysis shows that uncertainties can be large if
      the laser spot size or the modulation frequency is not properly chosen. Here we
      propose an alternative approach based on TDTR to measure in-plane anisotropic
      thermal conductivity using a highly elliptical pump (heating) beam. The highly
      elliptical pump beam induces a quasi-one-dimensional temperature profile on the
      sample surface that has a fast decay along the short axis of the pump beam. The
      detected TDTR signal is exclusively sensitive to the in-plane thermal
      conductivity along the short axis of the elliptical beam. By conducting TDTR
      measurements as a function of delay time with the rotation of the elliptical pump
      beam to different orientations, the in-plane thermal conductivity tensor of the
      sample can be determined. In this work, we first conduct detailed signal
      sensitivity analyses for both techniques and provide guidelines in determining
      the optimal experimental conditions. We then compare the two techniques under
      their optimal experimental conditions by measuring the in-plane thermal
      conductivity tensor of a ZnO [11-20] sample. The accuracy and limitations of both
      methods are discussed.

PMID- 30278765
TI  - X-ray detector based on Mn doped MgAl2O4 and Si photodiode.
AB  - Luminescence properties of Mn doped MgAl2O4 crystals connected with the Si PIN
      photodiode (PD) have been evaluated for X-ray detector applications. Mn doped
      MgAl2O4 crystals emit green colored luminescence peaking at around lambda = 520
      nm with CuKalpha irradiation. The intensity of the output signal from Si PD
      increases linearly with the X-ray intensity of CuKalpha generated with the X-ray
      tube at a current from 2 mA to 40 mA. The intensity of the X-ray excited
      luminescence is strongest in the specimen with 3.0 mol. % Mn. Afterglow
      luminescence is weak in the specimen with 2.0 mol. % Mn. Mn doped MgAl2O4
      crystals connected with the Si PD is considered to be a useful X-ray detector.

PMID- 30278766
TI  - Portable and noise-tolerant magnetic field generation system.
AB  - We have successfully developed a portable pulsed magnetic field generation system
      incorporating a number of techniques to avoid the effects of noise, including
      shielding, a self-power capability, and a high-capability semiconductor switch.
      The system fits into a cubical box less than 0.5 m in linear dimensions and can
      easily be installed in experimental facilities, including noisy environments such
      as high-power laser facilities. The system can generate a magnetic field of
      several tesla sustainable for several tens of microseconds over a spatial scale
      of several centimeters. In a high-power laser experiment with Gekko-XII, the
      system operated stably despite being subjected to a high level of electrical
      noise from laser shots of 600 J.

PMID- 30278767
TI  - Tunnel diode resonator for precision magnetic susceptibility measurements in a mK
      temperature range and large DC magnetic fields.
AB  - Precision radio-frequency measurements of the magnetic susceptibility using the
      tunnel diode resonator (TDR) technique are used to study the delicate effects in
      magnetic and superconducting materials. High resolution (in ppb range)
      measurements are particularly important for studies of the London and Campbell
      penetration depths in a superconductor and for the investigation of magnetic
      transitions in (anti)ferromagnets. Due to the small rf magnetic-excitation in a
      mOe range, the TDR is especially useful at low-temperatures in a mK range, if
      Joule heating generated in the TDR circuitry is efficiently removed and the
      circuit is stabilized with sub-mK precision. Unfortunately, the circuit has
      significant magnetic field dependence, and therefore, most of the precision TDR
      measurements at low-temperatures were conducted in zero magnetic field. In this
      work, we describe the design of a setup for precision TDR measurements in a
      dilution refrigerator down to ~40 mK with a 14 T superconducting magnet. The key
      features of our design are the separated electronics components and the placement
      of the most field sensitive parts in the field-compensated zone far from the
      center of solenoid as well as the heat-sinking at a higher temperature stage. The
      performance of the working setup is demonstrated using several superconductors.

PMID- 30278768
TI  - The generation of mega-gauss fields on the Cornell beam research accelerator.
AB  - Intense magnetic fields modify quantum processes in extremely dense matter,
      calling for precise measurements in very harsh conditions. This endeavor becomes
      even more challenging because the generation of mega-gauss fields in a laboratory
      is far from trivial. This paper presents a unique and compact approach to
      generate fields above 2 MG in less than 150 ns inside a volume on the order of
      half a cubic centimeter. Magnetic insulation, keeping plasma ablation close to
      the wire surface, and mechanical inertia, limiting coil motion throughout the
      current discharge, enable the generation of intense magnetic fields where the
      shape of the conductor controls the field topology with exquisite precision and
      versatility, limiting the need for mapping magnetic fields experimentally.

PMID- 30278769
TI  - Amplifier for scanning tunneling microscopy at MHz frequencies.
AB  - Conventional scanning tunneling microscopy (STM) is limited to a bandwidth of a
      few kHz around DC. Here, we develop, build, and test a novel amplifier circuit
      capable of measuring the tunneling current in the MHz regime while simultaneously
      performing conventional STM measurements. This is achieved with an amplifier
      circuit including a LC tank with a quality factor exceeding 600 and a home-built,
      low-noise high electron mobility transistor. The amplifier circuit functions
      while simultaneously scanning with atomic resolution in the tunneling regime,
      i.e., at junction resistances in the range of giga-ohms, and down towards point
      contact spectroscopy. To enable high signal-to-noise ratios and meet all
      technical requirements for the inclusion in a commercial low temperature, ultra
      high vacuum STM, we use superconducting cross-wound inductors and choose
      materials and circuit elements with low heat load. We demonstrate the high
      performance of the amplifier by spatially mapping the Poissonian noise of
      tunneling electrons on an atomically clean Au(111) surface. We also show
      differential conductance spectroscopy measurements at 3 MHz, demonstrating
      superior performance over conventional spectroscopy techniques. Further, our
      technology could be used to perform impedance matched spin resonance and
      distinguish Majorana modes from more conventional edge states.

PMID- 30278770
TI  - Note: Simultaneous measurement of in-plane and out-of-plane displacement by using
      orthogonally polarized self-mixing grating interferometer.
AB  - In this paper, we present an orthogonally polarized self-mixing grating
      interferometer (SMGI) for simultaneous measurement of in-plane and out-of-plane
      displacements. The measurement ranges in both directions are limited only by the
      length of grating. The orthogonally polarized lights emitted from a birefringent
      He-Ne laser are separated and enter the grating at +/-1st-order Littrow angles.
      The diffraction beams re-enter the laser cavity and cause self-mixing
      interference. To differentiate the orthogonally polarized lights and obtain high
      resolution, phase modulation technique is introduced to extract phases from the
      orthogonally polarized SMGI signals. The measurement results show that the
      proposed system can reach a submicron accuracy in the experiment. This work
      provides a good way to achieve high precision two-dimensional displacement
      measurement with a robust system configuration.

PMID- 30278772
TI  - Calibration methods for the simultaneous measurement of the impulse, mass loss,
      and average thrust of a pulsed plasma thruster.
AB  - This paper presents calibration devices and methods for the measurement of
      electric thruster performance parameters using a seesaw-type thrust stand to
      measure the mass loss of solid propellant in a vacuum. In previous studies,
      impact hammers and electrostatic combs have been manufactured for the calibration
      of the thrust and impulse using seesaw-type thrust stands. However, these
      conventional devices rely on self-calibration, which means that the input
      delivered by the device in unknown, and must undergo a calibration process
      themselves. In this paper, the manufactured calibration devices successfully
      reproduced known impulses, thrusts, and mass losses in a vacuum. By reproducing
      known inputs based on known masses, the proposed calibration devices can omit the
      conventionally required self-calibration process. The calibration results showed
      linear relations between outputs and known inputs and agreed with the theoretical
      values to within an error of 10%. Additionally, the uncertainties of all known
      inputs were less than 1.5%. On the basis of these results, the average thrust,
      impulse, and mass loss were measured using a calibrated thrust stand for the
      first time. The cumulative impulses obtained from the measured impulse and
      average thrust agreed with each other to within an error of 5%. The error of the
      measured mass loss per 1000 shots with respect to the actual mass loss measured
      using an electronic balance ranged from 1% to 17%.

PMID- 30278771
TI  - A suite-level review of the neutron powder diffraction instruments at Oak Ridge
      National Laboratory.
AB  - The suite of neutron powder diffractometers at Oak Ridge National Laboratory
      (ORNL) utilizes the distinct characteristics of the Spallation Neutron Source and
      High Flux Isotope Reactor to enable the measurements of powder samples over an
      unparalleled regime at a single laboratory. Full refinements over large Q ranges,
      total scattering methods, fast measurements under changing conditions, and a wide
      array of sample environments are available. This article provides a brief
      overview of each powder instrument at ORNL and details the complementarity across
      the suite. Future directions for the powder suite, including upgrades and new
      instruments, are also discussed.

PMID- 30278773
TI  - An automated instrument for polarization-enhanced broadband nuclear quadrupole
      resonance (NQR) spectroscopy.
AB  - An automated instrument for improving the sensitivity of nuclear quadrupole
      resonance (NQR) spectroscopy is presented. The device is capable of pre
      polarizing samples within a custom Halbach-type permanent magnet and then moving
      them into an external probe for zero-field NQR detection. Polarization transfer
      between protons and nitrogen (14N) nuclei in the sample occurs during
      demagnetization, thus increasing the amplitude of the detected NQR signals. The
      sample motion profile is completely programmable, thus providing a high level of
      control over the sample position and velocity for optimizing the polarization
      transfer process for various samples. Moreover, the magnet and motion controller
      are combined with a shielded sample probe and ultra-broadband front-end
      electronics (both designed in-house) to realize a complete scientific instrument
      for 14N NQR experiments. Compared with previous work in the field, the system is
      designed to be programmable, robust, and easy to use. Experimental results from
      several samples are also presented.

PMID- 30278774
TI  - RHEGAL: Resistive heating gas enclosure loadframe for in situ neutron scattering.
AB  - In situ neutron scattering is a powerful tool to reveal materials atomic
      structural response such as phase transformation, lattice straining, and texture
      under external stimuli. The advent of a high flux neutron source such as the
      Spallation Neutron Source (SNS) allows fast measurement in even non-equilibrium
      conditions, i.e., phase transformation in steels. However, the commercial fast
      heating apparatus such as commercial physical simulation equipment is not
      designed for in situ neutron scattering, which limits its application to in situ
      materials research by using neutrons. Here we present a resistive heating gas
      enclosure loadframe (RHEGAL) for non-equilibrium phase transformation studies by
      using in situ neutron scattering, which takes the advantage of high flux neutron
      sources like SNS. RHEGAL enables fast resistive heating of metal samples to 1200 
      degrees C at a rate up to 60  degrees C/s in an inert atmosphere. It provides
      both horizontal and vertical positions for scattering optimization. The
      mechanical loading capability also allows in situ high temperature tension above
      the oxidation temperature limit. The optimized translucent neutron scattering
      window by silicon allows both reflection and transmission measurements, making
      this equipment applicable for neutron diffraction, small angle scattering, and
      imaging. To demonstrate the fast heating capability, the phase transformations of
      an example of advanced high strength steel heated at 3  degrees C/s and 30 
      degrees C/s were measured with the VULCAN engineering diffractometer, and the
      different phase transformation kinetics by neutron diffraction were presented.

PMID- 30278775
TI  - Glycoprotein VI Gene Variants Affect Pregnancy Loss in Patients With Platelet
      Hyperaggregability.
AB  - The aim of our study was to evaluate GP6 gene in patients with sticky platelet
      syndrome (SPS) and fetal loss. Platelet aggregability was tested with platelet
      rich plasma using PACKS-4 aggregometer (Helena Laboratories). High-resolution
      melting analysis on LightCycler 480 II (Roche Diagnostics) was used for single
      nucleotide polymorphism (SNP) genotyping. We examined 64 patients with SPS and 54
      control participants. We found significantly higher occurrence of 5 SNPs in
      patients with SPS versus controls (rs1671152, rs1654433, rs1613662, rs1654416,
      and rs2304167). Moreover, the haplotype analysis showed a significantly higher
      occurrence of 7 haplotypes in patients with SPS compared to controls (acgg and
      aagg in GP6_5reg haplotype; ccgt in GP6_3reg haplotype; gg and ta in GP6_REG
      haplotype; SKTH and PEAN in GP6_PEAN haplotype). Our results, especially higher
      occurrence of 4 nonsynonymous variants within the coding region, support the idea
      that GP6 polymorphisms are associated with the platelet hyperaggregability
      accompanied by fetal loss.

PMID- 30278776
TI  - Venous Thromboembolism: A Survey of Oral Anticoagulant Preferences in the
      Treatment of Challenging Patient Populations.
AB  - Venous thromboembolism (VTE) is a highly morbid condition with several available
      oral anticoagulant treatment options. Numerous studies have been published
      comparing warfarin to direct oral anticoagulants; however, several populations
      remain underrepresented in these reports. We surveyed members of The Venous
      ThromboEmbolism Network U.S. working group regarding their oral anticoagulant
      preferences for the treatment of VTE in different and challenging populations. In
      individuals with VTE and no other medical comorbidities, respondents preferred
      either rivaroxaban (48.7%) or apixaban (48.7%). Apixaban (53.3%) was preferred in
      elderly individuals with an increased risk of bleeding. Warfarin was preferred in
      individuals with liver or kidney dysfunction (42% and 47%), altered metabolism
      (>55%), and antiphospholipid antibody syndrome (84.2%). Low-molecular-weight
      heparin was preferred in individuals with malignancy (56.6%), followed by
      edoxaban (23.7%). These findings may help guide clinicians when choosing an
      anticoagulant in these challenging situations and demonstrate the urgent need for
      additional study in these groups.

PMID- 30278777
TI  - Effect of Exercise on Behavioral Symptoms and Pain in Patients With Dementia
      Living in Nursing Homes.
AB  - OBJECTIVES: Examine the effects of a 6-month exercise intervention on
      neuropsychiatric symptoms, pain, and medication consumption in older people with
      dementia (PWD) living in nursing homes (NH). METHODS: Ninety-one older PWD living
      in NH performed a 6-month structured exercise intervention (n = 44) or a social
      activity intervention (n = 47). Neuropsychiatric symptoms were measured by the
      neuropsychiatric inventory (NPI), pain was assessed using the Algoplus scale, and
      dementia-related drug prescriptions were obtained for all participants. RESULTS:
      Between-group analysis found a nonsignificant difference that could be of
      clinical relevance: a 4-point difference in the NPI and 1.3-point difference in
      the reduction of the number of medications favoring exercisers. No significant
      differences were found for pain, and a trend was found for an increase in
      medication consumption in the social group. CONCLUSION: Exercise effects did not
      differ from social intervention effects on neuropsychiatric symptoms, pain, and
      medication consumption in older PWD living in NH.

PMID- 30278778
TI  - Effect of short-term mechanical stimulation on the salivary concentrations of
      vitamin C, vitamin E, total antioxidant capacity and total oxidant status.
AB  - Oxidative stress biomarkers of oral and systemic diseases can be found in saliva.
      However, there is no uniformity for the saliva collection time in these kinds of
      analyses and saliva composition may change because of mechanical stimulation.
      Therefore, the aim of this work was to determine the effect of mechanical
      stimulation for 10 min on the concentrations of vitamin C, vitamin E, total
      antioxidants and total oxidants in saliva. Saliva samples from individuals of
      both sexes, aged between 18 and 38 years, were collected for 10 min at 2
      minintervals. Saliva flow rate in each 2 min period was measured, as well the
      total oxidant state, the total antioxidant capacity, vitamin C and vitamin E
      concentrations. All analyses were performed in triplicate and were determined
      using colorimetric tests. The results were analysed using t-test, Friedman's test
      and analysis of variance (ANOVA) for repeated measures. Mauchly's sphericity test
      was applied and, if necessary, technical corrections were made using the
      Greenhouse-Geisser test. We found no significant difference between the amounts
      of saliva produced across the collection times. Total oxidant status, total
      antioxidant capacity, vitamin C and vitamin E concentrations remained stable.
      Based on our findings, saliva can be collected for 10 min or less with
      masticatory stimulation without any variations in the concentration of the
      variables analysed. However, we suggest using saliva samples after two minutes of
      mechanical stimulation.

PMID- 30278779
TI  - Cytokines and statin therapy in chronic obstructive pulmonary disease patients.
AB  - Cytokines are biological response modifiers involved in the pathophysiology of
      chronic obstructive pulmonary disease (COPD). This study investigated the
      potential use of cytokines as disease severity biomarkers in COPD patients and
      the possible effect of statin therapy on cytokine expression. Possible
      associations between cytokines, body mass index (BMI) and smoking have also been
      studied. Cytokines IFN-gamma, IL-2, IL-12 p70, TNF-alpha, TNF-beta, IL-4, IL-5,
      IL-6, IL-10, IL-1beta and IL-8 were measured in the plasma of 100 clinically
      stable COPD patients using a fluorescent bead immunoassay on a flow cytometer.
      When patients were grouped according to Global Initiative for Chronic Obstructive
      Lung Disease (GOLD) stage (A-D), no significant differences in cytokine
      concentrations were found (p > .05). Significantly decreased concentrations of IL
      1beta, IL-2, IL-4, IL-8, IL-10, IL-12p70 and TNF-alpha were found in COPD
      patients receiving statin therapy in comparison with COPD patients not receiving
      statin therapy (p < .05). COPD patients with increased BMI (>25) had decreased IL
      2 (p=.038), IL-8 (p = .039) and IL-10 (p = .005) concentrations compared to
      normal BMI (20-25) patients. Current COPD smokers had increased concentrations of
      IL-5 (p = .037) compared to former COPD smokers. Hierarchical cluster analysis
      showed several patterns of measured cytokines in serum of patients with stable
      COPD. Statin therapy is associated with decreased expression of selected Th1 and
      Th2 cytokines in COPD, and this effect could be of relevance in COPD patients
      with increased cardiovascular risk. Concentrations of Th1 and Th2 cytokines in
      plasma cannot be used as biomarkers of disease severity or progression of COPD.

PMID- 30278780
TI  - Comparative immunogenicity assessment of biosimilars.
AB  - The first anticancer biosimilars have entered clinical use, with many others
      under clinical development. Like all biologics, biosimilars may elicit unwanted
      immune responses that can significantly impact clinical efficacy and safety. Head
      to-head immunogenicity assessment of biosimilars and their reference biologics
      should, therefore, be a critical component of a biosimilar's clinical development
      program. Various bioanalytical platforms may be used to detect and characterize
      immune responses, each having relative strengths and weaknesses. To fully
      recognize the clinical relevance of such data, regulators must be able to
      interpret immunogenicity results in an assay-specific context as well as in
      perspective of clinical pharmacology, efficacy and safety. Herein, we discuss
      current challenges imposed by global regulatory requirements for immunogenicity
      assessment of biosimilars.

PMID- 30278781
TI  - Antioxidant and anti-inflammatory effects of pomegranate peel extracts on bovine
      mammary epithelial cells BME-UV1.
AB  - Pomegranate peel extracts (PPE) were tested for the first time on BME-UV1, a
      valid cellular model to study the bovine mammary epithelial metabolism, to
      evaluate the effects on the oxidative stress and inflammatory status. Based on
      the statistical analysis of MTT data, PPE at 0.1, 1.0 and 10 MUg/mL resulted not
      cytotoxic after 24 h, 48 h and 7 days of treatment. At the same concentrations,
      PPE induced a reduction of ROS production elicited by the addition of hydrogen
      peroxide or lipopolysaccharide evidencing an antioxidant effect confirmed also by
      a decrease of malondialdehyde. At 10 MUg/mL, PPE reduced pro-inflammatory
      cytokines expressions showing an anti-inflammatory effect on BME-UV1 treated with
      lipopolysaccharide. Although in vivo experiments are necessary, the results of
      this study are promising for future applications of PPE as feed supplement for
      dairy cattle, in particular around calving, when the animals are more subject to
      oxidative stress and inflammatory diseases.

PMID- 30278782
TI  - Accessing and Recruiting a Community-Based Sample of Men of Mexican Origin to
      Explore Intimate Partner Violence.
AB  - INTRODUCTION: Vulnerable populations are at greater risk for the burden of
      disease and negative health outcomes including alcohol abuse, high-risk sexual
      behavior, and intimate partner violence (IPV). Moreover, health disparities
      experienced by vulnerable populations are mediated by socioeconomic, ethnic, and
      racial factors. Risk factors for IPV perpetration are exacerbated by cultural and
      gender norms, particularly among men of Mexican origin. PURPOSE: To discuss
      research methods used in a community-based sample of men of Mexican origin and
      ways to overcome recruitment barriers through community engaged approaches.
      DISCUSSION: Barriers can impede sampling, recruitment, and enrollment of
      vulnerable populations (e.g., IPV) but can be overcome. Strategies include:
      qualitative research methods, identifying key informants, and community
      engagement approaches, such as listening to the concerns of the community,
      incorporating the community's knowledge to inform and improve the study, and
      building rapport to establish trust. CONCLUSION: Conducting research within
      vulnerable populations can be challenging but can be mitigated by incorporating
      multiple strategies. Thus, allowing researchers to gain access and valuable
      insight into traditionally underrepresented and understudied populations.

PMID- 30278783
TI  - Longitudinal study of medication use in caregivers of people with Alzheimer's
      disease - Kuopio ALSOVA study.
AB  - BACKGROUND: The longitudinal pattern of medication use among family caregivers of
      people with dementia is not well understood, despite the potential for medication
      over- or under-use. OBJECTIVES: To investigate caregiver medication use over a
      five-year follow-up using data obtained via self-report and from a national
      prescription register, and compare agreement between medication data obtained
      from the two sources. METHODS: Medication data for 222 family caregivers of
      people with Alzheimer's disease were obtained via self-report and from the
      Finnish Social Insurance Institution. Generalised estimating equations, Kappa
      statistics and related samples Wilcoxon signed rank test were used to analyse
      medication use over time. RESULTS: The mean number of medications used by
      caregivers increased from 3.4 to 4.1 (self-reported current regular medications)
      and 2.4 to 2.8 (reimbursed prescription medications during the past 90 days) over
      five years (p < 0.001). Significantly, more medications were identified via self
      report (mean 3.6, SD = 3.3) than the national prescription register (mean 2.6, SD
      = 2.4, Z= -12.300, p < 0.001). Agreement between the two data sources was good
      for cardiovascular medications and anti-hypertensives (Kappa = 0.883-0.967, p <
      0.001) and medications for acid-related disorders (Kappa = 0.508-0.092, p <
      0.001). Agreement was moderate for analgesics (Kappa = 0.281-0.477, p < 0.001)
      and psychotropics (Kappa = 0.281-0.562, p < 0.002). The proportion of caregivers
      using five or more medications increased from 27.5% to 44.6% (self-report), and
      16.7% to 27.7% (register) (p < 0.001). CONCLUSION: Caregivers use an increasing
      number of medications in the first five years of caring for persons with
      dementia, and self-report using a higher number of medications than data from the
      national prescription register suggest.

PMID- 30278784
TI  - Assessment of Orthodontic Burden of Care in Patients With Unilateral Complete
      Cleft Lip and Palate.
AB  - OBJECTIVE: To assess the orthodontic burden of care of patients from a Brazilian
      rehabilitation center (Hospital for Rehabilitation of Craniofacial Anomalies,
      University of Sao Paulo [HRAC-USP]). DESIGN: Retrospective. SETTING: Hospital for
      Rehabilitation of Craniofacial Anomalies, University of Sao Paulo. INTERVENTIONS:
      One hundred files of unilateral complete cleft lip and palate patients who had
      consecutively finished orthodontic rehabilitation at HRAC-USP were evaluated from
      January 2011 to January 2013. The duration of orthodontic treatment, number of
      visits, kilometers traveled, number of appliances and surgical procedures
      performed were recorded. The sample was divided into 2 subgroups according to
      severity the interarch relation (Goslon Yardstick score) at the beginning of
      orthodontic treatment. Mann-Whitney test was applied for intergroup comparison (
      P < .05). RESULTS: For the total sample (n = 100), the mean time of orthodontic
      treatment was 140.2 months, the mean number of orthodontic appointments was 61.8,
      the mean number of appliances was 10, the mean number of surgical procedures was
      6.2, and the mean distance traveled to attend the center for orthodontic
      appointments was 38,978.5 km. The subgroup with the most severe malocclusion
      (Goslon yardsticks scores 4 and 5) showed a longer orthodontic treatment length,
      greater number of surgical procedures, and longer distance traveled than those
      presenting Goslon yardstick scores 1, 2, and 3. CONCLUSION: Patients with greater
      severity of the initial malocclusion experienced a higher burden of care than
      patients with less severity of the initial malocclusion. To reduce the burden of
      care, research and efforts should focus on minimizing maxillary growth deficiency
      related to primary surgery.

PMID- 30278785
TI  - Development of a core outcome set for trials investigating the long-term
      management of bronchiectasis.
AB  - Heterogeneity in outcomes measured in trials limits accurate comparison of
      bronchiectasis studies. A core outcome set (COS) is an agreed, standardized set
      of outcomes that should be measured in trials for specific clinical areas. A COS
      for bronchiectasis could encourage consistency in future studies. An overview of
      systematic reviews and qualitative study on outcome selection in bronchiectasis
      informed an initial list of outcomes. A Delphi panel ( n = 86) rated the
      importance of each outcome from 1 to 9 in 3 sequential questionnaires, as a means
      to achieve consensus: 1-3 = 'of limited importance'; 4-6 = 'important, but not
      critical'; and 7-9 = 'critical'. Outcomes rated 'critical' by >=70% of the panel
      were added to the COS. Eighty-two participants responded to the first
      questionnaire. Attrition between each questionnaire was 5%. After 3 rounds of
      questioning, 18 outcomes exceeded the threshold for consensus and were included
      in the COS. This study has achieved consensus on 18 outcomes that should be
      measured in trials of interventions for bronchiectasis. Selection of the highest
      ranked outcomes may represent a pragmatic means for comparison. Further research
      is required to condense the number of outcomes selected and to determine its
      relevance to interventions.

PMID- 30278786
TI  - Validation of electronic medical data: Identifying diabetes prevalence in general
      practice.
AB  - BACKGROUND: Electronic medical records are increasingly used for research with
      limited external validation of their data. OBJECTIVE: This study investigates the
      validity of electronic medical data (EMD) for estimating diabetes prevalence in
      general practitioner (GP) patients by comparing EMD with national Bettering the
      Evaluation and Care of Health (BEACH) data. METHOD: A "decision tree" was created
      using inclusion/exclusion of pre-agreed variables to determine the probability of
      diabetes in absence of diagnostic label, including diagnoses (coded/free-text
      diabetes, polycystic ovarian syndrome, impaired glucose tolerance, impaired
      fasting glucose), diabetic annual cycle of care (DACC), glycated haemoglobin
      (HbA1c) > 6.5%, and prescription (metformin, other diabetes medications). Via SQL
      query, cases were identified in EMD of five Illawarra and Southern Practice
      Network practices (30,007 active patients; from 2 years to January 2015). Patient
      based Supplementary Analysis of Nominated Data (SAND) sub-studies from BEACH
      investigating diabetes prevalence (1172 GPs; 35,162 patients; November 2012 to
      February 2015) were comparison data. SAND results were adjusted for number of GP
      encounters per year, per patient, and then age-sex standardised to match age-sex
      distribution of EMD patients. Cluster-adjusted 95% confidence intervals (CIs)
      were calculated for both datasets. RESULTS: EMD diabetes prevalence (T1 and/or
      T2) was 6.5% (95% CI: 4.1-8.9). Following age-sex standardisation, SAND
      prevalence, not significantly different, was 6.7% (95% CI: 6.3-7.1). Extracting
      only coded diagnosis missed 13.0% of probable cases, subsequently identified
      through the presence of metformin/other diabetes medications (*without other
      indicator variables) (6.1%), free-text diabetes label (3.8%), HbA1c result*
      (1.6%), DACC* (1.3%), and diabetes medications* (0.2%). DISCUSSION: While
      complex, proxy variables can improve usefulness of EMD for research. Without
      their consideration, EMD results should be interpreted with caution. CONCLUSION:
      Enforceable, transparent data linkages in EMRs would resolve many problems with
      identification of diagnoses. Ongoing data quality improvement remains essential.

PMID- 30278788
TI  - [Clinical profile of adolescents being treated for problematic internet use].
AB  - OBJECTIVES: This study highlights the clinical profile of adolescents having
      consulted with an addiction treatment center (ATC) in Quebec for a problematic
      internet use (PIU) to develop knowledge about these specific clients and
      precisely target their needs relative to treatment. METHOD: The study was
      conducted with 80 adolescents between ages 14 and 17 (M = 15.59) who had
      consulted with an ACT for a PIU. Adolescents have participated in an interview
      documenting internet use patterns and their consequences, mental health disorder
      co-occurrence, and family and social relationships. RESULTS: The sample was
      constituted of 75 boys (93.8%) and 5 girls (6.3%), who spent an average of 55.8
      hours (SD = 27.22) per week on internet for non-school or professional
      activities. Almost all of these youths (97.5%) presented a co-occurring mental
      health disorder, and more than 70% had seeked help last year for a psychological
      problem. Results show that 92.6% feel their internet use significantly hinders
      their family relationships, and 50% feel it impedes their social relationships.
      CONCLUSIONS: This study shows the multiple difficulties experienced by
      adolescents in need of a treatment for their PIU. The presence of co-occurring
      mental health disorders and relational difficulties among them underlines the
      need to develop and implement in ACTs integrated assessments and treatments that
      target not only online activities, but also all of life domains that can be
      affected by PIU. CLINICAL IMPLICATIONS: - PIU adolescents are mainly boys who
      report problematic use of video games. - Almost all young people who consult for
      PIU have comorbid mental health problems and difficulties in their relation. -
      The study highlights the need to offer to this clientele an integrated assessment
      and treatment services that target all areas of their lives who are likely to be
      affected, to contribute or maintain the PIU. LIMITATIONS: - This study was
      conducted with a convenience sample and the results are representative of young
      people who have visited a treatment center for addiction. The generalization of
      results to all adolescents with PIU is limited. - Considering that PIU are
      subject to cultural influence, the scope of this study is limited to populations
      living in a culture similar to that of Quebec and Canada.

PMID- 30278787
TI  - Effects of the oral, direct factor Xa inhibitor edoxaban on routine coagulation
      assays, lupus anticoagulant and anti-Xa assays.
AB  - Edoxaban is an oral direct factor Xa inhibitor for prophylaxis and treatment of
      thromboembolic disorders. The effects on common coagulation assays are clinically
      valuable information and in certain clinical situations a quick assessment of the
      anticoagulant is wanted. Our aim was to investigate the effect of edoxaban on
      routine coagulation methods and evaluate anti-Xa assays, commonly used for other
      direct factor Xa inhibitors, for estimation of the drug concentration. Edoxaban
      was spiked to plasma samples from healthy subjects in the concentration range 0
      742 ug/L and analyzed using different reagents for activated partial
      thromboplastin time (APTT) and prothrombin time (PT). Assays for antithrombin,
      activated protein C resistance, lupus anticoagulant (LA) and chromogenic anti-Xa
      assays were also included. Edoxaban displayed similar effects in vitro to other
      oral direct Xa inhibitors. The concentration needed to double the coagulation
      time varied between assays and reagents; 539-758 ug/L for the APTT and between
      329 and 2505 ug/L for the PT. Edoxaban gave false high antithrombin activities in
      assays based on Xa-inhibition. Two integrated assays for LA, both based on
      activation with dilute Russell's viper venom, displayed different results.
      Chromogenic anti-Xa assays displayed linear dose-response curves with edoxaban up
      to approximately 500 ug/L. In conclusion, therapeutic concentrations of edoxaban
      variably affect different coagulation assays, and even different reagents within
      an assay group. In comparison with other oral Xa-inhibitors, the in vitro effects
      of edoxaban were more similar to rivaroxaban than apixaban. For measurement of
      edoxaban concentration in plasma, it is possible to use the chromogenic anti-Xa
      assays.

PMID- 30278789
TI  - Electroencephalographic Biomarkers for Treatment Response Prediction in Major
      Depressive Illness: A Meta-Analysis.
AB  - OBJECTIVE:: Reducing unsuccessful treatment trials could improve depression
      treatment. Quantitative EEG (QEEG) may predict treatment response and is being
      commercially marketed for this purpose. The authors sought to quantify the
      reliability of QEEG for response prediction in depressive illness and to identify
      methodological limitations of the available evidence. METHOD:: The authors
      conducted a meta-analysis of diagnostic accuracy for QEEG in depressive illness,
      based on articles published between January 2000 and November 2017. The review
      included all articles that used QEEG to predict response during a major
      depressive episode, regardless of patient population, treatment, or QEEG marker.
      The primary meta-analytic outcome was the accuracy for predicting response to
      depression treatment, expressed as sensitivity, specificity, and the logarithm of
      the diagnostic odds ratio. Raters also judged each article on indicators of good
      research practice. RESULTS:: In 76 articles reporting 81 biomarkers, the meta
      analytic estimates showed a sensitivity of 0.72 (95% CI=0.67-0.76) and a
      specificity of 0.68 (95% CI=0.63-0.73). The logarithm of the diagnostic odds
      ratio was 1.89 (95% CI=1.56-2.21), and the area under the receiver operator curve
      was 0.76 (95% CI=0.71-0.80). No specific QEEG biomarker or specific treatment
      showed greater predictive power than the all-studies estimate in a meta
      regression. Funnel plot analysis suggested substantial publication bias. Most
      studies did not use ideal practices. CONCLUSIONS:: QEEG does not appear to be
      clinically reliable for predicting depression treatment response, as the
      literature is limited by underreporting of negative results, a lack of out-of
      sample validation, and insufficient direct replication of previous findings.
      Until these limitations are remedied, QEEG is not recommended for guiding
      selection of psychiatric treatment.

PMID- 30278790
TI  - A Population-Based Analysis of the Relationship Between Substance Use and
      Adolescent Cognitive Development.
AB  - OBJECTIVE:: Alcohol and cannabis misuse are related to impaired cognition. When
      inferring causality, four nonexclusive theoretical models can account for this
      association: 1) a common underlying vulnerability model; 2) a neuroplasticity
      model in which impairment is concurrent with changes in substance use but
      temporary because of neuroplastic brain processes that restore function; 3) a
      neurotoxicity model of long-term impairment consequential to substance use; and
      4) a developmental sensitivity hypothesis of age-specific effects. Using a
      developmentally sensitive design, the authors investigated relationships between
      year-to-year changes in substance use and cognitive development. METHOD:: A
      population-based sample of 3,826 seventh-grade students from 31 schools
      consisting of 5% of all students entering high school in 2012 and 2013 in the
      Greater Montreal region were assessed annually for 4 years on alcohol and
      cannabis use, recall memory, perceptual reasoning, inhibition, and working
      memory, using school-based computerized assessments. Multilevel regression
      models, performed separately for each substance, were used to simultaneously test
      vulnerability (between-subject) and concurrent and lagged within-subject effects
      on each cognitive domain. RESULTS:: Common vulnerability effects were detected
      for cannabis and alcohol on all domains. Cannabis use, but not alcohol
      consumption, showed lagged (neurotoxic) effects on inhibitory control and working
      memory and concurrent effects on delayed memory recall and perceptual reasoning
      (with some evidence of developmental sensitivity). Cannabis effects were
      independent of any alcohol effects. CONCLUSIONS:: Beyond the role of cognition in
      vulnerability to substance use, the concurrent and lasting effects of adolescent
      cannabis use can be observed on important cognitive functions and appear to be
      more pronounced than those observed for alcohol.

PMID- 30278791
TI  - Impaired Motion Processing in Schizophrenia and the Attenuated Psychosis
      Syndrome: Etiological and Clinical Implications.
AB  - OBJECTIVE:: The ability to perceive the motion of biological objects, such as
      faces, is a critical component of daily function and correlates with the ability
      to successfully navigate social situations (social cognition). Deficits in motion
      perception in schizophrenia were first demonstrated about 20 years ago but remain
      understudied, especially in the early, potentially prodromal, stages of the
      illness. The authors examined the neural bases of visual sensory processing
      impairments, including motion, in patients with schizophrenia (N=63) and
      attenuated psychosis (clinical high risk) (N=32) compared with age-matched
      healthy control subjects (N=67). METHOD:: Electrophysiological recordings during
      stimulus and motion processing were analyzed using oscillatory (time frequency)
      approaches that differentiated motion-onset-evoked activity from stimulus-onset
      sensory-evoked responses. These were compared with functional MRI (fMRI) measures
      of motion processing. RESULTS:: Significant deficits in motion processing were
      observed across the two patient groups, and these deficits predicted impairments
      in both face-emotion recognition and cognitive function. In contrast to motion
      processing, sensory-evoked stimulus-onset responses were intact in patients with
      attenuated psychosis, and, further, the relative deficit in motion-onset
      responses compared with stimulus-onset responses predicted transition to
      schizophrenia. In patients with schizophrenia, motion detection deficits mapped
      to impaired activation in motion-sensitive visual cortex during fMRI. Additional
      visual impairments in patients with schizophrenia, not present in patients with
      attenuated psychosis, implicated other visual regions, including the middle
      occipital gyrus and pulvinar thalamic nucleus. CONCLUSIONS:: The study findings
      emphasize the importance of sensory-level visual dysfunction in the etiology of
      schizophrenia and in the personal experience of individuals with the disorder and
      demonstrate that motion-processing deficits may predate illness onset and
      contribute to impaired function even in patients with attenuated psychosis.

PMID- 30278792
TI  - Intellectual Disability and Psychotic Disorders in Children: Association With
      Maternal Severe Mental Illness and Exposure to Obstetric Complications in a Whole
      Population Cohort.
AB  - OBJECTIVE:: Children of mothers with severe mental illness are at significantly
      increased risk of developing intellectual disability. Obstetric complications are
      also implicated in the risk for intellectual disability. Moreover, children of
      mothers with severe mental illness are more likely to be exposed to obstetric
      complications. The purpose of this study was to examine the independent and joint
      contributions of familial severe mental illness and obstetric complications to
      the risk of intellectual disability. METHOD:: Record linkage across Western
      Australian whole-population psychiatric, inpatient, birth, and midwives'
      registers identified 15,351 children born between 1980 and 2001 to mothers with
      severe mental illness and 449,229 children born to mothers with no mental
      illness. Multivariable models were adjusted for paternal psychiatric status,
      parental intellectual disability, and other family and sociodemographic
      covariates. RESULTS:: The risk of intellectual disability was increased among
      children of mothers with severe mental illness compared with children of
      unaffected mothers. The impact varied across maternal diagnostic groups. For
      children of mothers with schizophrenia, the unadjusted odds ratio was 3.8 (95%
      CI=3.0, 4.9) and remained significant after simultaneous adjustment for exposure
      to obstetric complications and other covariates (odds ratio=1.7, 95% CI=1.3,
      2.3). The odds ratio for exposure to obstetric complications also remained
      significant after adjustment (odds ratio=1.7, 95% CI=1.6, 1.8). For intellectual
      disability of a genetic basis, the adjusted odds ratio for maternal schizophrenia
      was elevated but not statistically significant. Among children with intellectual
      disability, 4.2% later developed a psychotic disorder, compared with 1.1% of
      children without intellectual disability. CONCLUSIONS:: Maternal severe mental
      illness and exposure to obstetric complications contribute separately to the risk
      of intellectual disability, suggesting potentially different causal pathways.

PMID- 30278793
TI  - Cross-cultural adaptation and validation of the ABIS questionnaire for French
      speaking amputeesFrench validation of the ABIS questionnaire.
AB  - BACKGROUND: The Amputee Body Image Scale (ABIS) and its shortened version (ABIS
      R) are self-administered questionnaires to measure body image perception of
      amputee. Our aim was to assess the validity and reliability of the French ABIS
      (ABIS-F and ABIS-R-F). METHODS: Ninety-nine patients were included. The cross
      cultural adaptation was performed according to the recommendations. Construct
      validity was assessed by measuring the correlation between ABIS-F or ABIS-R-F
      scores and quality of life, pain, anxiety, and depression. Internal consistency
      was measured with Cronbach's alpha. The standard error of measurement, smallest
      detectable change, Bland and Altman limits of agreement, and intraclass
      correlation were the measures of agreement and reliability. RESULTS: A highest
      body image disturbance was associated with lowest quality of life, higher pain,
      and higher anxiety, and depression. Cronbach's alpha was 0.91/0.89 (ABIS-F/ABIS-R
      F). The standard error of measurement was 5.35/2.28 (ABIS-F/ABIS-R-F). The
      smallest detectable change was 14.82/6.31 (ABIS-F/ABIS-R-F). The mean difference
      in ABIS-F score was -3.90 with limits of agreement from -18.71 to 10.92. For ABIS
      R-F, the mean difference was -2.12 with limits of agreement from -8.43 to 4.19.
      Intraclass correlation was 0.87/0.82 (ABIS-F/ABIS-R-F). CONCLUSIONS: The French
      versions ABIS-F and ABIS-R-F share similar psychometric properties, both are as
      reliable, but ABIS-R-F has a better response structure and is more feasible.
      Implications for rehabilitation The quality of life of amputees is impacted by
      their satisfaction with body image The Amputee Body Image Scale questionnaire
      measures this perception and is available for French-speaking amputees The
      Standard Errors of Measurement proposed could be useful for clinical and research
      purposes Both ABIS and ABIS-R showed satisfactory construct validity, internal
      consistency, and reliability The shortened version has a better response
      structure and is more readily feasible.

PMID- 30278794
TI  - Care coordinator assistants: Job satisfaction and the importance of teamwork in
      delivering person-centered dementia care.
AB  - As the prevalence of persons with dementia increases, a larger, trained, and
      skilled healthcare workforce is needed. Attention has been given to models of
      person-centered care as a standard for dementia care. One promising role to
      deliver person-centered care is the care coordinator assistant. An inquiry about
      care coordinator assistant's job satisfaction is reasonable to consider for
      retention and quality improvement purposes. We evaluated care coordinator
      assistants' job satisfaction quantitatively and qualitatively. This study was
      part of a Centers for Medicare & Medicaid Services Health Care Innovation Award
      to the Indiana University School of Medicine. Sixteen care coordinator
      assistants, predominately female, African American or Caucasian, college
      graduates with a mean age of 43.1 years participated. Care coordinator assistants
      wrote quarterly case reports to share stories, lessons learned, and/or the impact
      of their job and completed the revised Job Satisfaction Inventory and Job in
      General scales during the second year of the Centers for Medicare & Medicaid
      Services award. For the Job Descriptive Index subscales promotion, supervision,
      and coworkers and Job in General, care coordinator assistants scored similar to
      normative means. Care coordinator assistants reported significantly higher
      satisfaction on the work subscale and significantly lower satisfaction on the pay
      subscale compared to normative data. Care coordinator assistants completed 119
      quarterly case reports. Job satisfaction and teamwork were recurring themes in
      case reports, referenced in 47.1% and 60.5% of case reports, respectively. To
      address the demands of increasing dementia diagnoses, care coordinator assistants
      can constitute a compassionate, competent, and satisfied workforce. Training care
      coordinator assistants to work together in a team to address the needs of persons
      with dementia and caregivers provides a viable model of workforce development
      necessary to meet the growing demands of this population.

PMID- 30278795
TI  - Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in
      pediatric patients.
AB  - Objective This study aimed to analyze the clinical characteristics and prognosis
      of pediatric idiopathic pulmonary hemosiderosis (IPH). Methods Pediatric IPH
      cases that were diagnosed at West China Second University Hospital, Sichuan
      University between 1996 and 2017 were reviewed. Follow-up data from 34 patients
      were collected. Results A total of 107 patients were included (42 boys and 65
      girls). The median age was 6 years at diagnosis. The main manifestations of the
      patients were as follows: anemia (n = 100, 93.45%), cough (n = 68, 63.55%),
      hemoptysis (n = 61, 57%), fever (n = 23, 21.5%), and dyspnea (n = 23, 21.5%).
      There were relatively few pulmonary signs. The positive rates of hemosiderin
      laden macrophages in sputum, gastric lavage fluid, and bronchoalveolar lavage
      fluid were 91.66%, 98.21%, and 100%, respectively. Seventy-nine patients were
      misdiagnosed. A total of 105 patients were initially treated with
      glucocorticoids, among whom 102 survived and three died. Among the followed up
      patients, two died and 32 survived, among whom 10 presented with recurrent
      episodes. Conclusions The classic triad of pediatric IPH is not always present.
      The rates of misdiagnosis and recurrence of IPH are high. Early recognition and
      adequate immunosuppressive therapy are imperative for improving prognosis of IPH.

PMID- 30278796
TI  - Serum NGAL and FGF23 may have certain value in early diagnosis of CIN.
AB  - AIMS: This study aimed to assess whether neutrophil gelatinase-associated
      lipocalin (NGAL) and fibroblast growth factor 23 (FGF23) could be reliable
      biomarkers for early diagnosis of contrast-induced nephropathy (CIN). METHODS:
      202 patients who underwent percutaneous coronary intervention (PCI) were included
      in the research. All subjects were divided into CIN group and non-CIN group.
      Serum NGAL and FGF23 were evaluated before and 0, 1, and 2 days after PCI. Serum
      levels of these two markers were compared intra-group and among groups. Receiver
      operating characteristic (ROC) analysis and logistic regression models were
      conducted to assess the diagnostic performance of NGAL and FGF23 in detecting
      CIN. RESULTS: When compared with baseline values, serum levels of both NGAL and
      FGF23 in all subjects increased after PCI, and the values peaked 1 day after PCI,
      but the changing was greater in CIN group. There were obvious differences between
      two groups in serum NGAL after 1, 2 days, and similar differences present in
      serum FGF23 after 1 day. ROC analysis showed that the area under the curve (AUC)
      of relative values (percent change from the baseline) in NGAL after 1 day was
      0.899 (95% CI: 0.834-0.964, p = .000), the optimum cutoff was 49% (sensitivity =
      80%, specificity = 92.4%). And the AUC in FGF23 was 0.814 (95% CI: 0.733-0.894, p
      = .000), the optimum cutoff was 20% (sensitivity = 73.3%, specificity = 87.6%).
      Both serum NGAL and serum FGF23 could improve the clinical models in identifying
      CIN. CONCLUSIONS: NGAL and FGF23 may have certain value in early diagnosis of
      CIN.

PMID- 30278797
TI  - Clinical and pathologic characteristics of pauci-immune anti-myeloperoxidase
      antibody associated glomerulonephritis with nephrotic range proteinuria.
AB  - BACKGROUND: Heavy proteinuria in antineutrophil cytoplasmic antibody (ANCA)
      associated glomerulonephritis (GN) is usually considered to be associated with
      immune deposits in renal biopsy. Nephrotic ANCA GN without immune deposits (pauci
      immune) is rare and has not been studied specially. In this study characteristics
      of these patients are to be investigated. METHODS: Clinical and pathological
      characteristics from 20 kidney biopsy-proven pauci-immune anti-myeloperoxidase
      antibody-associated GN patients with nephrotic proteinuria were analyzed and were
      compared with ANCA GN patients without nephrotic proteinuria. RESULTS: Acute
      kidney injury (AKI) and gross hematuria were much prevalent but extra-renal
      involvement was less prevalent in pauci-immune ANCA GN with nephrotic proteinuria
      than in pauci-immune ANCA GN without nephrotic proteinuria. No more severe
      hypoalbuminemia, hypercoagulability, hyperlipidemia or higher thrombosis
      incidence were found between two groups. Compared with patients without nephrotic
      proteinuria, patients with nephrotic proteinuria had more prevalent crescentic
      category in histopathology. Proteinuria decreased quickly after treatment but
      much poorer renal prognosis was found in pauci-immune ANCA GN with nephrotic
      proteinuria. The results of urinary albumin to total protein ratio and urinary
      protein electrophoresis showed pauci-immune ANCA GN with nephrotic proteinuria
      had obvious non-selective proteinuria. CONCLUSIONS: Pauci-immune ANCA GN with
      nephrotic proteinuria do not have more severe hypoalbuminemia, hypercoagulability
      or hyperlipidemia than patients without nephrotic proteinuria. Non-selective
      proteinuria might be the reason. However, pauci-immune ANCA GN with nephrotic
      proteinuria have more prevalent crescentic category in histopathology, higher
      incidence of AKI, gross hematuria and poorer renal prognosis despite of good
      sensitivity to therapy of proteinuria.

PMID- 30278798
TI  - Glycogen synthase kinase (GSK) 3 in pregnancy and parturition: a systematic
      review of literature.
AB  - INTRODUCTION: Human reproduction is a multifaceted process reliant on proper
      blastocyst implantation, placental and fetal membrane development, and delivery
      of a healthy baby. Multiple factors and pathways have been reported as critical
      machineries for cell differentiation and survival during pregnancy, and most of
      them involve glycogen synthase kinase (GSK) 3alpha/beta for cell differentiation
      and survival and for maintaining cellular homeostasis. Several reports on GSK3's
      functional role exist; however, the specific role of GSK3 in reproductive tissues
      and its contribution to normal or abnormal parturition are still unclear. To fill
      this knowledge gap, a systematic review of literature was conducted to better
      understand the functional role of GSK3 in various intrauterine tissues during
      implantation, pregnancy, and parturition. METHODS: We conducted a systematic
      review of English literature published between 1980 and 2017 on GSK3's expression
      and function reported in reproductive tissues during pregnancy using 3 electronic
      databases (Web of Science, Medline, and ClinicalTrials.gov). Study selection,
      data extraction, and quality assessment were performed in duplicate by two
      independent reviewers. RESULTS: A total of 738 citations were identified; 80 were
      selected for full text evaluation and 25 were included for final review. GSK3's
      regulation and function were mostly studied in tissues and cells from placentas
      (12), fetuses (8), uteruses (6), and ovaries (2). Measurements of total GSK3 and
      its isoforms (alpha and/or beta) were determined mostly by Western blot analysis.
      GSK3 is primarily reported as a downstream responder of protein kinase B (AKT)-,
      Wnt-, and reactive oxygen species (ROS)-related pathways where it plays a
      critical role in cell survival and growth in reproductive tissues. CONCLUSIONS:
      GSK3 is functionally linked to blastocyst implantation, establishment of
      pregnancy, trophoblast migration and invasion, decidualization, and term and
      preterm labor. Few reports specifically studied GSK3's expression and function in
      any reproductive tissues; it has mostly been studied as a secondary signaler of
      various conserved cell signaling pathways. Lack of scientific rigor in studying
      GSK3's role in reproductive tissues makes this molecule's function still obscure.
      No studies have reported GSK3 in the cervix, and very few reports exist in
      myometrium and decidua. GSK3's functions are hardly studied in reproductive
      tissues, and several knowledge gaps have been identified that require more
      functional studies in reproductive biology.

PMID- 30278799
TI  - Maternal age and cardiovascular and metabolic disease outcomes: A retrospective
      cohort study using data from population-based electronic medical records.
AB  - OBJECTIVE: To evaluate whether a woman's age at first birth is associated with
      cardiovascular risk and metabolic health outcomes (cardiometabolic outcomes) by
      age 45. METHODS: This is a retrospective, population-based cohort study that uses
      electronic health record data from the largest health fund in Israel. Women aged
      34-39 at baseline (2004-2006) free of chronic diseases were identified as
      nulliparous at baseline and were followed up to 10 years (through 2016). The
      cohort was divided into three groups based on their age at first birth: younger
      parturients (ages 35-39), older parturients (ages 40-44), and never had children.
      The percentage of adverse pregnancy events and cardiometabolic outcomes at age 45
      were compared across these three groups as well as to women in the general
      population. Cardiovascular risk and metabolic health outcomes were defined as:
      Type 2 diabetes, obesity, hypertension, cardiovascular disease, and Framingham
      risk score. METHODS AND RESULTS: Out of a group of 126 121 women aged 34-39 at
      baseline, 9979 were nulliparous and free of comorbidities. Over the course of the
      follow-up, there were 952 younger parturients and 673 older parturients who had
      their first birth, and 8354 women who remained persistent nulliparous. While
      older parturients had more adverse pregnancy events, there was no difference in
      rates of cardiometabolic outcomes between the two parturient groups, and they
      both had lower rates than the persistent nulliparous and the general population.
      CONCLUSIONS: Parturients free of major chronic diseases who give birth at a later
      age do not have increased cardiometabolic outcomes in midlife as compared to a
      general population of women in a large retrospective cohort. Our results may
      support clinicians when counseling healthy women who are seeking advice regarding
      delaying their first pregnancy without a tradeoff on health outcomes.

PMID- 30278801
TI  - Red blood cells as an organ? How deep omics characterization of the most abundant
      cell in the human body highlights other systemic metabolic functions beyond
      oxygen transport.
AB  - INTRODUCTION: Recently, the classification of two 'novel' organs, the mesentere
      and interstitium, was saluted as a scientific breakthrough and disseminated into
      mainstream media. The novelty of these findings did not pertain to the
      characterization of some previously unexplored phenomena, rather to the
      appreciation that well-established tissues may play some hitherto unexplored
      functions critical to system homeostasis. Areas covered: Here we provocatively
      comment on the potential classification of red blood cells - by far the most
      abundant host cell in the human body (~ 83% of the total cells) - as an organ
      involved in many functions beyond gas transport. In this perspective article, we
      describe some of these functions with a special emphasis on the role erythrocytes
      play with respect to systemic metabolic homeostasis. We thus focus on how these
      functions modulate the cross talk of red blood cells among each other and with
      other cell types including immune cells. Expert commentary: The appreciation of
      RBCs as an organ impacting systemic metabolic homeostasis and other cell
      functions while engaging in complex metabolic activity beyond oxygen transport
      can foster the development of novel therapeutic interventions in pathologic
      hypoxemia, inflammation, neurodgenerative diseases, aging, and cancer.

PMID- 30278802
TI  - Emicizumab for hemophilia A with factor VIII inhibitors.
AB  - INTRODUCTION: Hemophilia is a serious bleeding disorder characterized by repeated
      bleeding episodes into joints and muscles which can lead to permanent
      disabilities. Treatment with factor replacement therapy has proven to be
      effective at preventing these complications; however, it can lead to formation of
      neutralizing antibodies termed inhibitors which significantly complicate the
      management of the disorder. These inhibitor patients suffer from increased
      morbidity and mortality and there has been a major unmet need for novel
      therapeutic approaches. Recently, one such therapy, emicizumab, has been licensed
      in the United States. Areas covered: This manuscript contains a detailed
      discussion of the mechanism of action, the clinical trial development program as
      well as a review of the benefits and risks of this novel agent. In addition,
      practical considerations for the use of the agent are also described. Expert
      commentary: Emicizumab represents a new class of medication for the treatment of
      hemophilia A which in the past has relied on factor replacement therapy and
      bypassing agent (alternative factor) therapy. Emicizumab fulfills two major unmet
      needs in patients with hemophilia who have FVIII inhibitors. First, it provides
      for a much more effective therapy for the prevention of bleeding and second it
      substantially reduces the treatment burden.

PMID- 30278803
TI  - Mediating role of caregiver burden among family caregivers of patients with
      Parkinson's disease in Mexico.
AB  - Objective This study examined the mediating role of caregiver distress on family
      factors and caregiver life satisfaction among an understudied population of
      Parkinson's disease caregiver in Mexico. Methods A cross-sectional design was
      used to examine psychosocial factors pertinent to caregiver of individuals with
      Parkinson's disease ( n = 95). Guided by a caregiver stress process model,
      relations among family factors (e.g., cohesion, flexibility, quality of
      functioning), gender, distress, and satisfaction with life among caregiver were
      examined. Mediation analyses were performed to test the role of caregiver
      distress on the associations between family factors, gender, and caregiver
      satisfaction with life. Results Mediation models demonstrated that caregiver
      distress fully mediated the relation between quality of family functioning and
      caregiver satisfaction with life and partially mediated the association between
      family flexibility and caregiver satisfaction with life. Caregiver gender did not
      emerge as a significant covariate, and null results were found in the model
      examining family cohesion as a predictor. Conclusion These results underscore the
      critical role of caregiver distress and family factors on features of caregiver
      well-being, notably satisfaction with life. This evidence also offers cross
      cultural evidence for the caregiver stress process model, which has primarily
      been observed in Western samples. Accordingly, the need to build and disseminate
      empirically supported family-based treatments that emphasize caregiver distress
      is warranted.

PMID- 30278804
TI  - Young ESAO challenges in artificial organs.

PMID- 30278800
TI  - Chymase inhibitors for the treatment of cardiac diseases: a patent review (2010
      2018).
AB  - INTRODUCTION: Chymase is primarily found in mast cells (MCs), fibroblasts, and
      vascular endothelial cells. MC chymase is released into the extracellular
      interstitium in response to inflammatory signals, tissue injury, and cellular
      stress. Among many functions, chymase is a major extravascular source for
      angiotensin II (Ang II) generation. Several recent pre-clinical and a few
      clinical studies point to the relatively unrecognized fact that chymase
      inhibition may have significant therapeutic advantages over other treatments in
      halting progression of cardiac and vascular disease. Area covered: The present
      review covers patent literature on chymase inhibitors for the treatment of
      cardiac diseases registered between 2010 and 2018. Expert opinion: Increase in
      cardiac MC number in various cardiac diseases has been found in pathological
      tissues of human and experimental animals. Meta-analysis data from large clinical
      trials employing angiotensin-converting enzyme (ACE) inhibitors show a relatively
      small risk reduction of clinical cardiovascular endpoints. The disconnect between
      the expected benefit associated with Ang II blockade of synthesis or activity
      underscores a greater participation of chymase compared to ACE in forming Ang II
      in humans. Emerging literature and a reconsideration of previous studies provide
      lucid arguments to reconsider chymase as a primary Ang II forming enzyme in human
      heart and vasculature.

PMID- 30278805
TI  - Association between renal damage markers and carotid atherosclerosis in Afro
      descendants with hypertension belonging to a minority ethnic group from Brazil.
AB  - Ethnicity appears to play an important role in the prevalence and severity of
      hypertension, renal disease, and atherosclerosis. A cross-sectional study was
      conducted, including 206 Afro-descendants with hypertension, living in the
      remaining quilombo communities. These subjects underwent a carotid intima-media
      thickness (CIMT) assessment. The presence of renal injury was assessed by: (1)
      The glomerular filtration rate (GFR) estimated by the formula CKD-EPI using
      creatinine and cystatin C and (2) Albuminuria (ACR >=30 mg/g). The Poisson
      distribution model was set with robust variance to identify factors associated
      with carotid atherosclerosis. The statistical analysis was performed using the
      Stata 12.0 software, adopting a significance level of 5%. Most subjects were
      women (61.65%); the average age was 61.32 (+/-12.44) years. Subjects (12.62%)
      were identified with GFR <60 mL/min/1.73 m2 and 22.8% with albuminuria. Patients
      (59.22%) presented with a high CIMT. In the adjusted regression model, age >=60
      years (PR: 1.232 [CI 95%:1.091-1.390], p value = .001), ACR >=30 mg/g (PR: 1.176
      [CI 95%: 1.007-1.373], p = .040), and GFR/CKD-EPI using cystatin C (PR: 1.250 [CI
      95%: 1.004-1.557], p = .045) were independently associated with carotid
      atherosclerosis. The occurrence of atherosclerotic lesions was high in the
      studied group. Age, albuminuria, and GFR (estimated by the formula CKD-EPI using
      cystatin C) influenced the prevalence of carotid atherosclerosis.

PMID- 30278806
TI  - Anterior humeral approach with nerve stimulator.
AB  - INTRODUCTION: The prevalence of radial nerve injury during surgery is as high as
      the prevalence of radial nerve injury due to trauma. The aim of this study is to
      minimize the risk of iatrogenic injury of radial nerve. MATERIALS AND METHODS:
      Fifty patients with middle or distal diaphysis fractures of humerus and 18
      patients with pseudoarthrosis at the same localizations were treated with
      surgery. Plate-screw fixation was performed with anterior approach in 43
      patients. Eleven patients had minimally invasive plate osteosynthesis, and 14
      patients had intramedullary nailing. The localization of the radial nerve was
      determined with nerve stimulator at the area of dissection. RESULTS: Iatrogenic
      radial nerve injury did not occur in patients treated with open reduction or
      minimally invasive approach. DISCUSSION: Nerve stimulator may be a method that
      decreases radial nerve injury, an iatrogenic complication. This method may be
      used in anterior approach and minimally invasive procedures.

PMID- 30278808
TI  - Population-based cardiovascular cohort studies in Uppsala.
AB  - The first population-based cohort study in Uppsala with the aim to study
      cardiovascular disease was initiated in 1970 (ULSAM). This cohort of 2300 middle
      aged men has since then been followed in a longitudinal fashion for almost 50
      years. This study has been followed by the PIVUS study, investigating 1000 men
      and women at ages 70, 75, and 80. A very detailed examination has also been
      performed in 500 subjects aged 50 years, the POEM study. In recent years, a high
      throughput study conducted in 13000 subjects has also been performed, named
      EpiHealth. Uppsala also collects data in 5,000 subjects in the nationwide SCAPIS
      study. Taken together, these cardiovascular-oriented studies constitute a very
      rich source for cardiovascular epidemiological research in Uppsala. This review
      summarizes the design of these studies and highlights some of the important
      results published based on data from these studies.

PMID- 30278807
TI  - Which is the most powerful adverse factor for autogenous access patency between
      diabetes and high arterial calcification burden?

PMID- 30278809
TI  - A three-dimensional virtual morphometry study of the sigmoid notch of the distal
      radius.
AB  - PURPOSE: Our primary objectives were to create a reliable, noninvasive method for
      three-dimensional morphometry of deep bony parameters within the sigmoid notch of
      the distal radius, to identify its morphological patterns, and to identify any
      significant variation between the left and the right wrists. Our secondary
      objectives were to obtain morphometric values that could represent our population
      and to identify any possible ethnic variations. METHODS: Computed tomography
      scans of 102 wrists from 51 healthy individuals were analyzed using a
      virtualization software. Four anatomical parameters at the distal radius sigmoid
      notch, namely, the radius of curvature, depth, version angle, and sagittal slope
      were measured. Morphological patterns of the sigmoid notch surface were
      identified. The results were statistically analyzed to assess the reliability of
      the technique and were compared with previously published literature. RESULTS:
      Comparing our findings with previously published values, our study revealed a
      slightly larger radius of curvature and sagittal slope, while revealing a smaller
      depth and version. We identified the S-type, C-type, and ski-slope morphological
      variants. The flat-face morphological variant, however, was not identified. The
      sigmoid notch at the left and right wrists were similar, except for the radius of
      curvature. CONCLUSION: This study demonstrates a noninvasive, fast, reliable, and
      reproducible technique for analyzing the sigmoid notch of the distal radius. In
      wrist injuries with intact distal radius sigmoid notch but involving comminuted
      fractures of the ulnar head, ulnar head replacement may be indicated. In such
      cases, analysis of the ipsilateral intact sigmoid notch would allow us to prepare
      an ulnar head prosthesis of appropriate size.

PMID- 30278810
TI  - An investigation into the impact of acute stress on encoding in older adults.
AB  - Acute psychological stress commonly occurs in young and older adults' lives.
      Though several studies have examined the influence of stress on how young adults
      learn new information, the present study is the first to directly examine these
      effects in older adults. Fifty older adults (M age = 71.9) were subjected to
      either stress induction or a control task before learning two types of
      information: a short video and a series of pictures. Twenty-four hours later,
      they were exposed to misleading information about the video and then completed
      memory tests for the video and pictures. Heart rate and cortisol measures suggest
      that a physiological stress response was successfully induced. Though pre
      encoding stress had little impact on memory accuracy, stress did influence errors
      of omission on the cued recall test for the video. Findings are discussed in the
      context of previous research examining the effects of stress on memory in older
      adults.

PMID- 30278811
TI  - Evaluation of pre- and post-dilution continuous veno-venous hemofiltration on
      leukocyte and platelet function in patients with sepsis.
AB  - OBJECTIVE: We investigated the differences in biocompatibility pre- and post
      dilution during continuous veno-venous hemofiltration in patients with sepsis,
      focusing on leukocyte and platelet function. PATIENTS AND METHODS: Subjects were
      12 patients with septic shock who underwent veno-venous hemofiltration for acute
      kidney injury between March 2016 and September 2017. The first six patients
      received pre-dilution veno-venous hemofiltration, and the next six patients
      received post-dilution veno-venous hemofiltration. The blood flow rate and
      filtration flow rate for veno-venous hemofiltration using a polysulfone
      hemofilter were set to 150 and 35 mL/min, respectively. Leukocyte and platelet
      counts were determined at 0 and 24 h after veno-venous hemofiltration
      commencement. Serum interleukin-6 and interleukin-10 levels, the induction rates
      of regulatory T cells, the expression rate of monocyte HLA-DR, neutrophil
      phagocytic and sterilizing ability, and platelet P-selectin expression rate were
      determined at 0, 6, and 24 h after veno-venous hemofiltration commencement.
      RESULTS: There were no significant differences in patient characteristics between
      the two groups. Serum interleukin-6 decreased over time during pre- and post
      dilution veno-venous hemofiltration. Serum interleukin-10 levels decreased during
      pre-dilution veno-venous hemofiltration, but remained unchanged during post
      dilution veno-venous hemofiltration. The Treg and platelet P-selectin expression
      rates significantly increased at 24 h compared to 0 h during post-dilution veno
      venous hemofiltration. Neutrophil phagocytic ability at 24 h was significantly
      decreased compared to that at 0 h during post-dilution veno-venous
      hemofiltration. No significant changes in leukocyte and platelet function were
      observed during pre-dilution veno-venous hemofiltration. CONCLUSION: Pre-dilution
      veno-venous hemofiltration demonstrates superior biocompatibility in terms of
      decreased leukocyte function and platelet activation in septic shock patients
      with acute kidney injury.

PMID- 30278812
TI  - Treatment of pain with intranasal fentanyl in pediatric patients in an acute care
      setting: a systematic review.
AB  - AIM: The primary objective of this review is to provide an updated, comprehensive
      overview on the efficacy of intranasal fentanyl (INF) for acute pain relief in
      the pediatric population. METHODS: Utilizing the Preferred Reporting Instructions
      for Systematic Reviews and Meta-Analyses (PRISMA), we were able to screen
      articles based on key words to reach a final number of 10 studies. RESULTS: All
      but one study showed that INF was efficacious for pain relief in this select
      pediatric population. CONCLUSION: It is evident that INF is efficacious for
      analgesia, but other agents should also be considered in this patient population.
      As a result, further research is needed to investigate the clinically efficacy of
      INF in an acute care setting for pediatric patients.

PMID- 30278813
TI  - Carfilzomib Induced Tumor Lysis Syndrome and Other Adverse Events.
AB  - In the area of multiple myeloma (MM) therapy, proteasome inhibitors (PI) have
      emerged with promising responses both in the first- and second-line setting.
      Carfilzomib (CFZ) is a second-generation, selective PI approved in 2012 for the
      treatment of relapsed/refractory multiple myeloma (RRMM) in patients who received
      2 prior therapies or have evidence of disease progression within 60 days of
      completion of last therapy. Its safety profile reported adverse events (AEs)
      ranging from drug-related AEs (nausea and vomiting), hematologic AEs (neutropenia
      and thrombocytopenia), and nonhematologic AEs (electrolyte imbalances). As CFZ
      use is gaining popularity, various hematological, renal, cardiovascular,
      pulmonary, and neurological toxicities have been reported. We are presenting this
      case to describe a rare occurrence of tumor lysis syndrome (TLS) with the use of
      this novel targeted therapy.

PMID- 30278814
TI  - Shock Index-A Useful Noninvasive Marker Associated With Age-Specific Early
      Mortality in Children With Severe Sepsis and Septic Shock: Age-Specific Shock
      Index Cut-Offs.
AB  - BACKGROUND: Aim of the study was to analyze the association of shock index (SI)
      from 0 to 6 hours with early mortality in severe sepsis/septic shock and to
      explore its age-specific cut-off values. To investigate association of change in
      SI over first 6 hours with early mortality. METHODS: A prospective cohort study
      of children (<14 years) admitted in emergency department, tertiary care hospital
      with severe sepsis or septic shock, divided into 3 groups: group 1: 1 month to <1
      year; group 2: 1 to <6 years; group 3: 6 to 12 years. Shock index (SI = heart
      rate/systolic blood pressure) measured at admission (X0) and hourly till 6 hours
      (X1-6). Primary outcome was death within 48 hours of admission. Area under
      receiver operating characteristic curves were constructed for SI (0-6). Optimal
      cut-offs of SI 0 and SI 6, maximizing both sensitivity and specificity were
      determined and positive and negative predictive values (PPV, NPV) were
      calculated. RESULTS: From 2015 to 2016, 120 children were recruited. Septic shock
      was present at admission in 56.7% children. Early mortality was 50%. All hourly
      shock indices (SI 0-6) were higher among nonsurvivors in group 2 ( P <= .03) and
      group 3 ( P < .001). In group 1, SI after 2 hours was higher in nonsurvivors ( P
      2-6: <= .02). Area under receiver operating characteristic curves (95% CI) for SI
      at 0 hour was 0.72 (0.5-0.9), 0.66 (0.5-0.8), and 0.77 (0.6-0.9) and at 6 hours
      was 0.8 (0.6-1), 0.75 (0.6-0.9), and 0.8 (0.7-1) in 3 groups. The cut-off values
      of SI 0 (sensitivity; specificity; PPV; NPV) in 3 groups: 1.98 (77; 75; 67; 83),
      1.50 (65; 65; 68; 63), and 1.25 (90; 67; 77; 83) and SI6: 1.66 (85; 80; 73; 89),
      1.36 (73; 70; 73; 70), and 1.30 (74; 73; 78; 69). Improvement of SI over 6 hours
      was associated with better outcome. Children with higher SI at both time points
      had higher mortality than those with SI score below the cut-offs ( P = .001).
      CONCLUSIONS: Age-specific SI cut-off values may identify children at high risk of
      early mortality in severe sepsis/septic shock and allow for better targeted
      management.

PMID- 30278816
TI  - A Novel Diabetic Mouse Model for Real-Time Monitoring of Clock Gene Oscillation
      and Blood Pressure Circadian Rhythm.
AB  - Diabetic patients have an increased prevalence of blood pressure (BP) circadian
      rhythm disruption, which is associated with an increased risk of target organ
      damage and detrimental cardiovascular events. Limited information is available
      regarding the role of clock genes in the disruption of BP circadian rhythm in
      diabetes due to the lack of a diabetic animal model that allows real-time
      monitoring of clock gene oscillation. Here, we generated a novel diabetic db/db
      mPer2Luc mouse model by crossing type 2 diabetic db/db mice with mPer2Luc knock
      in mice. The daily rhythms of BP, heart rate, locomotor activity, and food and
      water intake were acquired by radiotelemetry or using metabolic chambers. The
      daily oscillation of mPer2 bioluminescence was recorded by LumiCycle in real-time
      in tissue explants and using the IVIS system in vivo. Our results show that db/db
      mPer2Luc mice are obese, diabetic, and glucose intolerant. The db/db-mPer2Luc
      mice displayed a compromised BP daily rhythm, which was associated with disrupted
      daily rhythms in baroreflex sensitivity, locomotor activity, and metabolism, but
      not heart rate or food and water intake. The phase of the mPer2 daily oscillation
      was advanced to different extents in the explanted peripheral tissues from db/db
      mPer2Luc mice relative to control mice. In contrast, no phase shift was detected
      in mPer2 daily oscillations in the explanted SCN. Moreover, advanced phase shift
      of the mPer2 daily oscillation was detected in the liver, kidney and
      submandibular gland in vivo of db/db-mPer2Luc mice. In conclusion, the diabetic
      db/db-mPer2Luc mouse is a novel animal model that allows real-time monitoring of
      mPer2 circadian rhythms ex vivo and in vivo. The results from db/db-mPer2Luc mice
      suggest that the desynchrony of mPer2 daily oscillation in peripheral tissues
      contributes to the loss of BP daily oscillation in diabetes.

PMID- 30278815
TI  - Self-Reported Hearing Loss and Pure Tone Audiometry for Screening in Primary
      Health Care Clinics.
AB  - OBJECTIVE: To evaluate the performance of self-reported hearing loss alone and in
      combination with pure tone audiometry screening in primary health care clinics in
      South Africa. DESIGN: Nonprobability purposive sampling was used at 2 primary
      health care clinics. A total of 1084 participants (mean age 41.2 years; SD 15.5
      years; range 16-97 years, 74.0% female) were screened using self-report and
      audiometry screening. Those failing audiometric screening and a sample of those
      who passed audiometric screening were also assessed by diagnostic pure time
      audiometry, to confirm or negate the finding of a hearing loss. RESULTS: Four
      hundred and thirty-six participants (40.2%) self-reported a hearing loss with no
      significant association with gender or race. One hundred and thirty-six
      participant (12.5%) self-reported hearing loss and failed audiometry screening
      (35 dB HL at 1, 2, and 4 kHz). Combining self-report with a second stage
      audiometry screening revealed a high test accuracy (81.0%) for hearing loss,
      being most accurate (86.1%) to identify high-frequency hearing loss. CONCLUSION:
      While self-report of hearing loss is an easy and time-efficient screening method
      to use at primary health care clinics, its accuracy may be limited when used in
      isolation and it may not be sufficiently sensitive to detect hearing loss.
      Combining a simple audiometry screening as a second-stage screen can
      significantly improve overall performance and efficiency of the screening
      protocol.

PMID- 30278817
TI  - Characteristics of Mail-Order Pharmacy Users: Results From the Medical
      Expenditures Panel Survey.
AB  - BACKGROUND: There is a paucity of research on the population characteristics of
      mail-order pharmacy users. OBJECTIVE: This study utilized a nationally
      representative sample to examine the characteristics of mail-order pharmacy
      users. METHODS: This study used data from the 2012 Medical Expenditure Panel
      Survey (MEPS). The outcome variable was defined as whether the participant had
      used a mail-order pharmacy during the study year. Logistic regression was
      conducted to determine the factors which influence mail-order pharmacy use. All
      analyses incorporated MEPS sampling weights to adjust for the complex survey
      design. RESULTS: Among the 14,106 adults included, approximately 18% of them had
      used a mail-order pharmacy at least once to fill their prescription in 2012.
      Compared to community pharmacy users, mail-order pharmacy users were more likely
      to be white, older, married, have a higher family income, a higher educational
      level, have health insurance, and have a prescription with at least a 30-day
      supply. There is no difference in gender or urban/rural disparity. In addition,
      mail-order pharmacy users had a lower percentage of out-of-pocket costs.
      CONCLUSION: Mail-order pharmacy use was significantly associated with certain
      patient characteristics. Policymakers should consider these characteristics when
      promoting mail-order pharmacy use.

PMID- 30278818
TI  - Does the plasma refilling coefficient change during hemodialysis sessions?
AB  - The filtration coefficient in the Starling equation is an important determinant
      of plasma refilling during hemodialysis. A method for calculating from clinical
      data an estimate of the filtration coefficient, called the refilling coefficient,
      was proposed in the past. The assumption behind this method was that the only
      drive for refilling is the increase in plasma oncotic pressure, and the remaining
      Starling forces have negligible effect. The refilling coefficient was observed to
      decrease during hemodialysis, and this was interpreted as a change in the
      filtration coefficient. The purpose of our study was providing an alternative
      explanation for the behavior of the refilling coefficient and, using clinical
      data and mathematical modeling, to predict the values of the immeasurable
      Starling forces and provide the theoretical basis for the interpretation of the
      refilling coefficient as the filtration coefficient. Blood volume and
      bioimpedance data from 23 patients undergoing hemodialysis were used to calculate
      the refilling coefficient according to the original formulation and to fit a two
      compartment model of protein and fluid transport. The changes in the other
      Starling forces were non-negligible, ranging from 19% to 60% of plasma oncotic
      pressure. The results showed that the decrease observed in the refilling
      coefficient is likely caused by neglecting important changes in the Starling
      forces while deriving the equation for the refilling coefficient. When these
      Starling forces were taken into account, constant filtration coefficient and
      dynamic refilling coefficient provided an equivalent description of the data in
      most cases. However, this was not true for a subgroup of sessions, which suggests
      that additional factors may also be responsible for the observed decrease in the
      refilling coefficient.

PMID- 30278819
TI  - Outcomes of an accelerated nonsurgical management protocol for hip fractures in
      the elderly.
AB  - The majority of hip fractures in elderly patients are managed surgically with
      superior outcomes. However, for patients who refuse surgery or are deemed
      medically unfit, traction used to be the mainstay of nonsurgical treatment, which
      is associated with prolonged hospitalization and inpatient complications from
      immobility. This study, therefore, aims to evaluate the outcomes of an early
      wheelchair mobilization protocol as an alternative nonsurgical treatment option.
      This is a retrospective study of 87 elderly patients who were managed
      nonsurgically for their hip fractures over a 1-year period. The accelerated
      rehabilitation protocol did not have them on traction but were instead mobilized
      with assistance as soon as possible after admission. Variables collected
      electronically include patient demographics, fracture characteristics, inpatient
      mobilization milestones, inpatient complications, Modified Functional Ambulation
      Classification (MFAC), Modified Barthel Index (MBI) scores, and radiological
      findings. Patients who were younger, could sit up earlier and had a shorter
      length of stay, were able to ambulate better at 6 months ( p value < 0.05).
      Patients with femoral neck fractures and shorter length of stay had better MFAC
      scores. A total of 58% of patients with radiological follow-up had displacement
      of their fractures with age, type of fracture, and length of stay as predictors (
      p value < 0.05) The Charlson's score, day to sitting up, and day to transfer
      affect fracture healing ( p value < 0.05). The mean length of stay was 17 days
      and the 1-year mortality was 18%. Surgical therapy remains the preferred choice
      of management for patients with hip fractures. Early wheelchair mobilization
      leads to a shorter length of stay compared to traditional traction methods and
      comparable 1-year mortality rates with operative management. Despite this,
      complication rates remain high and only 48% of patients achieved ambulation by 1
      year, with healing in only 24% of fractures.

PMID- 30278820
TI  - Association between MPO-463G > A polymorphism and chronic kidney disease: a meta
      analysis.
AB  - BACKGROUND/OBJECTIVE: Previous studies have shown that MPO -463G > A (rs2333227)
      might be associated with chronic kidney disease (CKD) susceptibility, but sample
      sizes of those studies are relatively small. Hence, we decided to perform a meta
      analysis to evaluate the association. Methods/main results: Two investigators
      search databases systematically and independently. Odds ratios and 95% confidence
      intervals were used to pool the effect size. Four articles with 618 cases and 932
      controls in total were included in our meta-analysis. CONCLUSIONS: MPO -463G > A
      was not associated with CKD susceptibility in recessive model and homozygote
      comparison. MPO -463G > A was associated with increased risk of CKD in allelic
      comparison, heterozygote comparison and dominant model, however, the results
      lacked stability. Owing to insufficient data, the association between MPO -463G >
      A and CKD cannot be fully confirmed.

PMID- 30278821
TI  - Bearing Witness: Exploring the End-of-Life Needs of Homeless Persons and Barriers
      to Appropriate Care.
AB  - Traditional models of palliative care are largely inaccessible to homeless
      persons, and their preferences regarding end-of-life care are poorly understood.
      The purpose of the present scoping review is to summarize the burgeoning gray and
      academic literature on end-of-life care for homeless persons. Five medical
      databases, seven social science databases, and four gray literature databases
      were searched, resulting in 57 relevant titles. Six themes emerged: (a)
      Characteristics of homeless persons who require end-of-life care; (b) preferences
      and concerns of homeless persons approaching the end of life; (c) the role of
      spirituality for homeless persons at the end of life; (d) barriers to care at the
      patient, provider, and institutional or structural levels; (e) inclusive models
      of palliative care; and (f) implications for policy and practice. Practitioners
      and homeless persons must negotiate many obstacles in the provision and receipt
      of palliative care. However, there is tremendous potential and opportunity to
      improve the quality of life at the end of life for this vulnerable population.

PMID- 30278822
TI  - The effectiveness of cervical transforaminal epidural steroid injection for the
      treatment of neck pain due to cervical disc herniation: long-term results.
AB  - AIM: To investigate the long-term effect of fluoroscopy guided cervical
      transforaminal epidural steroid injection on neck pain radiating to the arm due
      to cervical disc herniation. MATERIALS & METHODS: 64 patients (26 women [40.6%],
      38 men [59.4%]; mean age, 44.9 +/- 12.1 years) who had received fluoroscopy
      guided cervical transforaminal epidural steroid injection for neck pain due to
      cervical disc herniation at least 1 year before were included in the study. The
      effectiveness of transforaminal epidural steroid injection was assessed using
      data obtained by medical records and a standardized telephone questionnaire.
      Multiple linear regression analysis was applied to evaluate the factors affecting
      the pain reduction after injection and the duration of treatment effect. RESULTS:
      The mean duration of neck pain symptom was 23.3 +/- 23.9 months. Most of the
      patients received a single injection (50 patients, 78.1%). The mean time since
      injection at the time of interview was 21.4 +/- 9.4 months. There was a
      significant reduction in mean pain visual analog scale (VAS [10 cm]) score, from
      8.6 +/- 1.4 at baseline to 3.2 +/- 2.5 at check visit two weeks after injection
      (p < 0.001). 52 patients (81.2%) reported pain relief of more than 50%. The mean
      duration of treatment effect was 13.3 +/- 9.44 months. Greater pain on the VAS
      was found to predict strongly the higher pain reduction and longer treatment
      effect (p = 0.042 and 0.011, respectively). CONCLUSION: The results suggested
      that cervical transforaminal epidural steroid injections might be an effective
      treatment for neck back pain radiating to the arm due to cervical disc
      herniation.

PMID- 30278823
TI  - Effects of adolescent exposure to behaviour change interventions on their HIV
      risk reduction in Northern Malawi: a situation analysis.
AB  - Understanding adolescents' translation of HIV and AIDS-related behaviour change
      interventions (BCI) knowledge and skills into expected behavioural outcomes helps
      us appreciate behaviour change dynamics among young people and informs evidence
      based programming. We explored the effects of adolescents' exposure to BCI on
      their HIV risk reduction in selected schools in Nkhatabay and Mzimba districts
      and Mzuzu city in Northern Malawi. The study used questionnaires as instruments.
      Data were collected between January and April 2017. Adolescent boys and girls [n
      = 552], ages 11-19 were randomly sampled to participate. Data analysis was
      through multiple regression and content analysis. Respondents included 324 female
      [58.7%] and 228 male [41.3%]. Multiple regression analysis indicated that
      exposure to BCI did not affect risk reduction in the study area. The best
      stepwise model isolated sexual experience ([Beta = .727, p = .0001, p < .05]) as
      having the strongest correlation with the dependent variable - risk reduction.
      BCI exposure was stepwise excluded ([Beta = -.082, p = .053, p > .05]). There was
      therefore no evidence against the null hypothesis of no relationship between
      adolescent exposure to BCI and their HIV risk reduction. Overall there was
      limited BCI knowledge and skills translation to behavioural risk reduction. The
      study points to the need to evaluate and redesign adolescent BCI in line with
      current behavioural dynamics among young people in Malawi. The findings have been
      used to inform the design and programming of a model to be tested for feasibility
      through a quasi-experiment in the second phase of our project.

PMID- 30278825
TI  - Evaluations versus stereotypes in emotion recognition: a replication and
      extension of Craig and Lipp's (2018) study on facial age cues.
AB  - Recently, Cognition and Emotion published an article demonstrating that age cues
      affect the speed and accuracy of emotion recognition. The authors claimed that
      the observed effect of target age on emotion recognition is better explained by
      evaluative than stereotype associations. Although we agree with their conclusion,
      we believe that with the research method the authors employed, it was impossible
      to detect a stereotype effect to begin with. In the current research, we
      successfully replicate previous findings (Study 1). Furthermore, by changing the
      comparative context, Study 2 provides a first test of age-stereotypes affecting
      emotions recognition. We discuss recommendations for future studies in the domain
      of social categorisation and emotion recognition.

PMID- 30278824
TI  - Effect of apigenin on apoptosis induced by renal ischemia/reperfusion injury in
      vivo and in vitro.
AB  - OBJECTIVES: This study aims to investigate the effects and molecular mechanisms
      of apigenin (ApI) on renal ischemia/reperfusion (I/R) injury in vivo and in
      vitro. METHODS: In vivo, the left renal artery was clamped for 45 min and the
      right kidney was removed to study renal I/R injury on Sprague-Dawley (SD) rats.
      ApI was injected at 60 min before renal ischemia. In vitro, renal tubular
      epithelial cells (HK-2) were pretreated with or without ApI (20 uM) for 60 min
      and then treated with hypoxia/reoxygenation (H/R). Renal function, histology,
      cells apoptosis, and cell viability were tested. Furthermore, the potential
      molecular mechanisms were assessed. RESULTS: ApI pretreatment could significantly
      alleviated the renal function and the pathological damage as well as cells
      apoptosis after I/R injury. Meanwhile, ApI treatment protects H/R induced HK-2
      cell apoptosis in vitro. The results of Western blot showed that ApI
      significantly increased the expressions of B-cell lymphoma 2 (Bcl-2) and phosphor
      AKt (p-AKt), Phosphoinositide 3-kinase (PI3K), while down-regulated the
      expressions of Caspase3 and Bax induced by H/R injury. CONCLUSIONS: ApI
      pretreatment can protect renal function against I/R injury and prevent renal
      tubular cells from apoptosis in vivo and in vitro which might through PI3K/Akt
      mediated mitochondria-dependent apoptosis signaling pathway.

PMID- 30278826
TI  - Decision Science: A New Hope.
AB  - Decision science is an area of enquiry that crosses many disciplines, from
      psychology to economics, each with their own perspective of decision-making.
      Traditionally, mathematicians have envisaged decision-making as a purely rational
      endeavor, whereas psychologists and behavioral economists have critiqued this
      narrative and suggested that cognitive short cuts are the real mechanisms behind
      how decisions are made. However, contemporary dual process theorists argue that
      two systems of the mind exist: system 1 (intuitive decision-making) and system 2
      (rational decision-making). The current review will present a relatively new
      metaphor for decision-making: the unified threshold model. This model is a global
      approach to decision-making which allows both intuitive and rational decision
      making processes to be explained in a more flexible manner than the dual process
      model. This review will introduce the reader to different types of threshold
      models (counter and diffusion), their assumptions, and their ability to explain
      decision-making behavior. Implications and future research will also be
      discussed. In summary, the aim of this review is to highlight that a rather than
      the unified threshold model of decision-making may give a more adequate
      explanation of decision-making data in comparison to previous models and
      theories.

PMID- 30278827
TI  - The BETACONNECTTM system: MS therapy goes digital.
AB  - Adherence to long-term treatment in chronic diseases such as multiple sclerosis
      is challenging. Many disease-modifying drugs (DMDs) for MS need to be injected.
      Injection devices may improve satisfaction with the injection procedure and boost
      adherence. Meeting patients' needs in handling and design of autoinjectors and
      other supporting elements may be key to successful therapy. The BETACONNECTTM
      system is a platform-based approach in DMD therapy. It combines autoinjector
      technology with digital tools to support patient self-management and facilitate
      communication between patients and healthcare providers. Here, we describe the
      components of the BETACONNECT system and review data on patients' satisfaction
      with the BETACONNECT autoinjector and how it compares to other devices.
      Additionally, we present first data on patients' satisfaction with the
      myBETAappTM.

PMID- 30278828
TI  - Social-emotional functioning in planned lesbian families: does biological versus
      non-biological mother status matter? An Italian pilot study.
AB  - To date, few studies have investigated the social-emotional functioning of
      planned lesbian families, wherein only one parent is the biological mother of the
      child. We examined if being a biological versus non-biological mother plays a
      role in planned lesbian couple functioning and mother-infant play interactions.
      The present study analyzes the attachment state of mind, couple alliance,
      parenting stress, and emotional availability in a sample of 40 mothers (20
      biological and 20 non-biological). The results showed that mothers' life-long
      attachment experiences and related mental states of mind, rather than biological
      relatedness between the parent and child, matter in a mother and child's
      emotional involvement in parent-child interaction. Furthermore, the results
      confirmed the different impact of the perceived quality of the couple alliance on
      biological and non-biological mothers. The findings obtained elucidated what
      counts in this new family typology, and constitute a heuristic solicitation for
      future studies to better understand the key factors and mechanisms implied in
      social-emotional functioning.

PMID- 30278829
TI  - Misoprostol-Induced Modification of the Notch Signaling Pathway in the Human
      Cervix.
AB  - The complex and multifactorial mechanisms that initiate and sustain the early
      labor process in the human uterus and cervix are still not well defined. Cervical
      maturation or ripening is likely to play a key role in preparing for birth.
      Prostaglandins have many different functions, including the regulation of uterine
      contractility and structure during pregnancy. The prostaglandin E1 analogue
      misoprostol is frequently used as a uterotonic and cervical ripening agent. Notch
      is a transmembrane receptor family responsible for basic functions such as cell
      survival, cell-cell communication, and differentiation and decidualization in
      pregnancy. However, our understanding of the effect of Notch signaling on the
      cervical ripening process is limited. This study was conducted in 20 pregnant
      women aged at 12 to 20 weeks of gestation undergoing medical abortion for fetal
      or maternal indications. True-Cut needle biopsies were taken from the anterior
      cervix 4 hours after oral ingestion of 200-MUg misoprostol or before the
      ingestion of misoprostol in the control group. Cervical expression of Notch
      receptors and ligands changed during the early phase of prostaglandin-induced
      preterm labor. Four hours after the administration of misoprostol, it was seen
      that N1 expression increased in muscle, while DLL1 and J2 expression increased in
      blood vessels, and N4 expression increased in macrophages. Knowing the mechanisms
      that initiate preterm birth is the most important step in planning the treatments
      and actions to prevent premature birth. As a signal that affects and perhaps
      directs preterm labor, Notch is prone to be an important actor in this process.

PMID- 30278831
TI  - Antigenotoxic effect of melatonin against mercuric chloride in human peripheral
      blood lymphocytes.
AB  - Melatonin (MLT) is an extraordinary antioxidant, which plays an important role in
      reducing reactive oxygen species (ROS) by scavenging them directly or indirectly.
      Mercury (Hg) is a heavy metal, which induces cytogenetic alterations via various
      mechanisms, leading to genotoxicity. It induces genotoxicity by enhancing the ROS
      chiefly. In the present study, the antigenotoxic effect of MLT was evaluated
      against mercuric chloride (HgCl2). All experiments were conducted in vitro in
      peripheral blood lymphocytes. Blood cultures were exposed to various
      concentrations of HgCl2 (2.63, 6.57, and 10.52 microM) for 24 h to study a range
      of genotoxic parameters. MLT (0.2 mM) supplementation, alone and in combination
      with the high concentration of Hg, was administered to blood cultures for 24 h.
      Genotoxic parameters, such as chromosomal aberrations (CAs; structural
      aberrations (chromatid gaps and breaks, chromosomal gaps and breaks) and
      numerical aberrations), micronuclei (MNs), and comet assay, were evaluated and
      analyzed using suitable statistical analysis. Hg treatment revealed a significant
      increase in CAs, MNs, and comet length. Co-supplementation of MLT along with Hg
      showed marked protection of these genotoxic end points in treated cultures. In
      conclusion, our findings suggest that MLT protects against Hg-induced
      augmentation in genotoxic indices because of its antioxidant property.

PMID- 30278830
TI  - An Automated Preprocessing Method for Diffuse Optical Tomography to Improve
      Breast Cancer Diagnosis.
AB  - The ultrasound-guided diffuse optical tomography is a noninvasive imaging
      technique for breast cancer diagnosis and treatment monitoring. The technique
      uses a handheld probe capable of providing measurements of multiple wavelengths
      in a few seconds. These measurements are used to estimate optical absorptions of
      lesions and calculate the total hemoglobin concentration. Any measurement errors
      caused by low signal to noise ratio data and/or movements during data acquisition
      would reduce the accuracy of reconstructed total hemoglobin concentration. In
      this article, we introduce an automated preprocessing method that combines data
      collected from multiple sets of lesion measurements of 4 optical wavelengths to
      detect and correct outliers in the perturbation. Two new measures of correlation
      between each pair of wavelength measurements and a wavelength consistency index
      of all reconstructed absorption maps are introduced. For phantom and patients'
      data without evidence of measurement errors, the correlation coefficient between
      each pair of wavelength measurements was above 0.6. However, for patients with
      measurement errors, the correlation coefficient was much lower. After applying
      the correction method to 18 patients' data with measurement errors, the
      correlation has improved and the wavelength consistency index is in the same
      range as the cases without wavelength-dependent measurement errors. The results
      show an improvement in classification of malignant and benign lesions.

PMID- 30278832
TI  - 41-Week Study of Progressive Diabetic Nephropathy in the ZSF1 fa/faCP Rat Model.
AB  - This symposium synopsis summarizes key results from a 41-week study of diabetic
      nephropathy (DN) in the type 2 diabetic ZSF1 fa/faCP rat model. During this
      study, we conducted longitudinal analysis of biomarkers, renal histopathology,
      ultrastructural assessment, renal quantitative image analysis, and transcriptome
      analysis of glomerular-enriched tissue. We concluded that there is translational
      value for using the ZSF1 rat model in mechanistic and therapeutic intervention
      efficacy studies for type 2 DN.

PMID- 30278833
TI  - Skeletal Anomalies in Senegalese Sole ( Solea senegalensis), an Anosteocytic
      Boned Flatfish Species.
AB  - Skeletal anomalies affect animal welfare and cause important economic problems in
      aquaculture. Despite the high frequency of skeletal problems in reared Solea
      senegalensis, there is lack of information regarding the histological features of
      normal and deformed vertebrae in this flatfish. The aim of this study was to
      describe the histopathological and radiographical appearance of vertebral body
      anomalies. Sixty-seven juvenile fish were radiographically examined 104 or 105
      days after hatching. Through radiographic images, vertebral segments were
      selected and processed for histopathological examination from 7 normal and 7
      affected fish. Alterations in bone shape and vertebral fusion were the most
      significant anomalies in the vertebral bodies. These alterations occurred most
      frequently between the last 3 abdominal vertebrae and the first 10 caudal centra.
      Radiographically, deformed vertebrae showed flattening of the endplates and
      narrowing of the intervertebral spaces. The radiographic findings concurred with
      the histological lesions where affected vertebrae exhibited irregular endplates
      and changes in trabecular bone. Radiolucent cartilaginous tissue was evident in
      the endplates of the deformed vertebra and, in some cases, the cartilaginous
      material extended from the growth zone into the intervertebral space. These
      changes were likely the primary alterations that led to vertebral fusion. Fused
      vertebrae were often reshaped and showed a reorganization of the trabeculae. The
      formation of metaplastic cartilage is frequent in a variety of anomalies
      affecting teleost species.

PMID- 30278834
TI  - Scheduled Emergency Trauma Operation: The Green Line Orthopedic Trauma Surgery
      Process Of Care.
AB  - BACKGROUND AND AIMS: Traditionally, patients requiring an orthopedic emergency
      operation were admitted to an inpatient ward to await surgery. This often led to
      congestion of wards and operation rooms while, for less urgent traumas, the time
      spent waiting for the operation often became unacceptably long. The purpose of
      this study was to evaluate the flow of patients coded green in a traffic light
      based coding process aimed at decreasing the burden on wards and enabling a
      scheduled emergency operation in Central Finland Hospital. MATERIALS AND METHODS:
      Operation urgency was divided into three categories: green (>48 h), yellow (8-48
      h), and red (<8 h). Patients, who had sustained an orthopedic trauma requiring
      surgery, but not inpatient care (green), were assigned an operation via green
      line process. They were discharged until the operation, which was scheduled to
      take place during office hours. RESULTS: Between January 2010 and April 2015,
      1830 green line process operations and 5838 inpatient emergency operations were
      performed. The most common green line process diagnoses were distal radial
      fracture (15.4% of green line process), (postoperative) complications (7.7%), and
      finger fractures (4.9%). The most common inpatient emergency operation diagnosis
      was hip fracture (24.3%). Green line process and inpatient emergency operation
      patients differed in age, physical status, diagnoses, and surgical procedures.
      CONCLUSION: The system was found to be a safe and effective method of
      implementing orthopedic trauma care. It has the potential to release operation
      room time for more urgent surgery, shorten the time spent in hospital, and reduce
      the need to operate outside normal office hours.

PMID- 30278835
TI  - Advances and Challenges on New Therapies and Clinical Targets of Acute Kidney
      Injury.
AB  - Acute kidney injury (AKI) is encountered in high-risk hospital settings where
      patients often suffer systemic illnesses, undergo surgery, or receive medications
      toxic to the kidneys. It is associated with high morbidity and mortality. Despite
      advances in understanding the pathophysiologic mechanisms involved in AKI, our
      ability to detect AKI early is limited, and outcomes remain unchanged. Once AKI
      is identified by the traditional markers of urine output and serum creatinine,
      the main therapeutic intervention is usually supportive care and/or renal
      replacement therapy until renal injury resolves. Urine biomarkers provide an
      optimistic future, offering the ability to identify patients at high risk for AKI
      such that preventative measures can be introduced. In this article, the
      etiologies of AKI are discussed, new biomarkers are assessed, and areas for
      further investigation are suggested.

PMID- 30278836
TI  - Immunohistochemical Profiling of Canine Intestinal T-Cell Lymphomas.
AB  - Human enteropathy-associated T-cell lymphoma (EATL) is classified into 2 distinct
      subgroups based on their phenotypes (type I and type II). Canine intestinal T
      cell lymphoma can be morphologically classified into large and small cell
      lymphomas (LCL and SCL, respectively). Their association with human EATL or
      immunohistochemical and biological features has not been well characterized. In
      this study, the immunohistochemical profiles of 17 cases of LCL and 33 cases of
      SCL were evaluated with markers used for human EATL classification.
      Morphologically, LCL was characterized by sheet-like proliferation of large to
      moderately sized neoplastic lymphocytes, with scant clear cytoplasm and
      pleomorphic, irregularly shaped nuclei containing distinctive nucleoli and
      scattered chromatin. In contrast, SCL was characterized by the proliferation of
      monomorphic small neoplastic lymphocytes, accompanied by infiltration of
      nonneoplastic plasma cells. Interestingly, 8 cases demonstrated mixed LCL and SCL
      morphologies. Granular cytoplasmic expression of granzyme B was observed in most
      LCL and SCL cases. Membranous expression of CD56 was demonstrated in only 2 of 17
      LCL and 0 of 33 SCL cases. Coexpression of CD20 by neoplastic T cells was
      observed in more SCL cases (16/33; 48%) than LCL cases (1/17; 6%). The CD56
      positive cells in 2 cases were negative for CD20. Although canine LCL shares
      common features with human EATL type I, canine SCL cells and human EATL type II
      differ in their immunophenotype. Canine intestinal T-cell lymphoma had a
      homogeneous immunophenotype regardless of cell morphology. The findings of this
      study may indicate large cell transformation of SCL rather than 2 distinct
      entities.

PMID- 30278837
TI  - Glomerulonephritis in Animal Models and Human Medicine: Discovery, Pathogenesis,
      and Diagnostics.
AB  - Glomerulonephritis (GN) is inflammation of glomeruli. The four major categories
      that cause human GN are mediated by immunoglobulin or complement or both, and
      they include (1) immune complex-mediated GN, (2) anti-glomerular basement
      membrane-mediated GN, (3) antineutrophil cytoplasmic autoantibody-mediated GN,
      and (4) complement factor 3 glomerulopathy mediated by complement dysregulation.
      Initiating processes include infection, autoimmunity, exogenous antigens, and
      neoplasia. Often there are predisposing and modulating genetic, epigenetic,
      and/or environmental factors. Animal models facilitated the recognition and
      elucidation of the pathogeneses of all four categories of GN, and they continue
      to be used in preclinical studies to identify and validate therapies for all four
      types of GN. Advanced diagnostic modalities (e.g., transmission electron
      microscopy and immunofluorescence) are helpful and sometimes required for the
      correct categorization of GN in humans and animals. This review provides
      historical background on the discovery of the different GN pathogeneses,
      describes some of the animal models used to discover and understand each GN
      pathogenic category, reviews the diagnostic classification of each category of
      GN, and compares human GN to spontaneous forms of nonhuman GN.

PMID- 30278838
TI  - Classification, Scoring, and Quantification of Cell Death in Tissue Sections.
AB  - The analysis and description of the appearance of cell death in tissue sections
      can add valuable information to research studies. The scoring/grading and
      quantification of cell death can be used either as part of a larger scoring
      scheme or as the final end point of a study. The degree of precision needed is
      study dependent and will be determined by the question being addressed and the
      complexity of the model. The methods one uses to quantify cell death are often
      guided by the tissue of interest. For example, in the brain, it is sometimes
      necessary to examine death of specific neuronal populations, whereas in more
      homogeneous tissue such as a tumor xenograft, quantification can be done on a
      whole-slide basis. In addition to examination of hematoxylin and eosin (HE)
      stained sections, immunohistochemistry can be employed to highlight areas of cell
      death or to identify specific types of cell death, for example, when
      differentiating apoptosis from necrosis. Automated quantification can be useful
      in generating statistically comparable data from HE-stained or immunolabeled
      samples. The rapidly expanding classification of cell death requires the use of
      multiple techniques to identify them in vivo. This article will provide examples
      of how different methods of examining and quantifying cell death are used in a
      variety of research areas, ranging from semiquantitative evaluation in HE-stained
      intestine to automated quantification of immunohistochemistry-immunolabeled brain
      and tumor xenografts. The recently described process of necroptosis will be
      discussed briefly, with the description and example of the methods used to
      differentiate this from apoptosis.

PMID- 30278839
TI  - Acute pesticide poisoning and related factors among farmers in rural Western
      Iran.
AB  - Although acute pesticide poisoning (APP) is known to be a major health concern
      among farmers in developing countries, knowledge of its prevalence and risk
      factors is limited. The purpose of this study was to investigate the prevalence
      and a broad range of potential work-related risk factors of APP among Iranian
      farmers and farm workers. This cross-sectional study was conducted in rural areas
      of the Twiserkan County in Iran. In this study, there were 474 farmers and farm
      workers who had used pesticide 1 week before data collection. Participants were
      selected from 104 villages. Data were gathered using a questionnaire and analyzed
      using STATA (version 14.2 SE). Binary logistic regression and multinomial
      logistic regression were employed. The results of this study showed that 286
      (60.3%) farmers and farm workers who applied pesticides suffered from work
      related APP. Most frequent APP symptoms were runny nose (29.8%) and headache
      (25.1%). Five risk factors were identified, including annual income ( p < 0.05),
      number of farming years (odds ratio (OR) = 0.31), number of spraying years (OR =
      2.40), place of pesticide storage (OR = 2.69), and type of sprayer ( p < 0.05).
      The results of this study indicated that APP is prevalent among the studied
      farmers. Some work-related factors play an important role in APP among Iranian
      rural farmers. In addition, the magnitude of these risk factors differed
      significantly by severity of acute and somatic pesticide poisoning.

PMID- 30278840
TI  - [Lipedema, the Unknown].
AB  - Lipedema, the Unknown Abstract. Lipoedema patients suffer from the widespread
      ignorance of their pathology. Considering its chronic, progressive and
      invalidating character, the early diagnosis of the disease must constitute the
      challenge of their caregivers in order to limit medical wanderings and the
      occurrence of complex clinical pictures. Treatments allow the reduction of
      lipedema and its long-term control. Management must be individualized according
      to the stage of the disease. The adherence of the patient, the supervision and
      the support of the practitioner are essential for obtaining the best results.

PMID- 30278841
TI  - ?

PMID- 30278842
TI  - ?

PMID- 30278843
TI  - [Advance Care Planning in Swiss Nursing Homes: Results of a Focus Group Study].
AB  - Advance Care Planning in Swiss Nursing Homes: Results of a Focus Group Study
      Abstract. Advance Care Planning (ACP) is a standardized consultation process in
      which patients define their therapy goals for future medical treatments with the
      help of a qualified health care facilitator. This way, ACP increases the
      probability that patients' wishes are fulfilled in case of decisional incapacity.
      The aim of this study was to implement a previously tested Swiss ACP program in
      two Swiss nursing homes to better understand the resulting processes, chances and
      difficulties. For this purpose focus group interviews were conducted after first
      implementation steps. The results show that an ACP implementation needs and must
      be coordinated with an approach covering the entire health system.

PMID- 30278844
TI  - [CME Answers: 'Fusobacterium nucleatum/naviforme - a Rare but Serious Cause for
      Pyogenic Liver Abscesses', Praxis No. 19].

PMID- 30278845
TI  - [A Slightly Different Gastroenteritis].
AB  - A Slightly Different Gastroenteritis Abstract. We report the case of a 81-year
      old female presenting with gastroenteritic symptoms and laboratory findings of a
      hemolytic anemia, thrombocytopenia and acute renal failure with fatal outcome. A
      hemolytic-uremic syndrome caused by an infection with EHEC was diagnosed. As a
      further complication, a urinary tract infection with K. pneumoniae was diagnosed
      and treated.

PMID- 30278846
TI  - [Surgical Treatment for Lipedema].
AB  - Surgical Treatment for Lipedema Abstract. Lipedema is a progressive disease that
      occurs in adolescence and affects one in nine women. The signs are limited to the
      lower limbs. Early signs are nonspecific, which is why the diagnosis is often
      ignored. Later, pain and heaviness of lower limbs become predominant. Finally, at
      an advanced stage, tissue fibrosis is associated with significant edema. At this
      stage, patients become severely disabled and bedridden. At the early stage, the
      treatment is conservative. Liposuction is indicated at the onset of pain. Its
      effectiveness pain and long-term control has been demonstrated on. Finally, late
      stages require heavy and complex surgeries combining dermolipectomy and
      liposuction.

PMID- 30278847
TI  - [CME: Ethylene Glycol Intoxication].
AB  - CME: Ethylene Glycol Intoxication Abstract. Ethylene glycol is a sweet-tasting
      alcohol used in common antifreeze and other industrial solutions. Without
      appropriate therapy, intoxication with ethylene glycol can result in severe
      metabolic acidosis, acute renal failure, and in death. After gastrointestinal
      resorption, hepatic metabolism starts with oxidation by alcohol dehydrogenase and
      results in severe anion gap metabolic acidosis. Other metabolic products are
      calcium oxalate crystals, which can deposit in several tissues like the kidneys
      and lead to acute tubular necrosis with reversible renal failure. The crucial
      therapeutic step is rapid inhibition of alcohol dehydrogenase with fomepizole or
      ethanol to avoid the formation of toxic metabolites. Additionally, haemodialysis
      is the most effective way to eliminate ethylene glycol as well as its toxic
      metabolites. If therapy is initiated rapidly, prognosis is favorable.

PMID- 30278848
TI  - [Lipedema: Which Etiological Pathways?]
AB  - Lipedema: Which Etiological Pathways? Abstract. The pathogenesis and epidemiology
      of lipedema are uncertain, and its diagnosis often delayed. Lipedema almost
      exclusively affects women, and a link to sex hormones is likely. The metabolic
      risk of this accumulation of fat in the lower limbs is not known, and weight loss
      has no impact on the morphology of the lower limbs. Due to the aesthetic
      discomfort and frequent initial misdiagnosis which results in inappropriate
      treatment, this condition can lead to significant psychological suffering for the
      patient. A better understanding of this disease is essential to the proper
      diagnosis and support for these patients, as well as guiding them in the
      effective care.

PMID- 30278849
TI  - ?

PMID- 30278850
TI  - [CME Rheumatology 17: Suture Granuloma or Gout?]

PMID- 30278851
TI  - [CME Laboratory 57/Answers: Preanalytics].

PMID- 30278852
TI  - Chronic Neurological Disease Due to Methylmercury Poisoning.
AB  - Organic mercury, especially methylmercury, poisoning causes chronic neurological
      disease predominantly affecting the brain. There have been documented exposures
      from eating fish from contaminated waters in Japan and in northwestern Ontario
      and in Iraq from eating bread made from seed wheat treated with methylmercuric
      fungicide. The neurological disease is called Minamata disease in Japan. Visual
      field constriction due to involvement of the calcarine cortex, sensory
      disturbance due to involvement of the somatosensory cortex, and cerebellar ataxia
      due to involvement of granule cell neurons of the cerebellum are common and
      characteristic features due to methylmercury poisoning. Other neurological
      features include dysarthria, postural and action tremor, cognitive impairment,
      and hearing loss and dysequilibrium. In contrast, peripheral nerve disease is
      more characteristic of inorganic mercury intoxication. Similarly, psychosis is
      more typical of exposure to inorganic mercury, which has been documented in the
      felt hat industry ("mad hatter"). Laboratory tests (e.g., on blood and hair and
      toenail samples) are of limited value in the assessment of chronic neurological
      disease due to mercury poisoning because they may not reflect remote neuronal
      injury due to mercury. Methylmercury also causes injury to fetal brains during
      development. There is no effective treatment.

PMID- 30278853
TI  - A randomized controlled trial of working memory and processing speed training in
      schizophrenia.
AB  - BACKGROUND: Although prior research has shown that cognitive training may improve
      cognition for schizophrenia patients, it is currently unclear which domains of
      cognition should be targeted in training. One suggestion is to target low- or mid
      level cognitive processes. In particular, working memory (WM) and processing
      speed (PS) have been named as two key areas of impairment in schizophrenia, and
      two domains of cognition that are linked to higher-order cognition and daily
      functioning. This study aimed to investigate the near-transfer (transfer of gains
      to related contexts), far-transfer (transfer of gains to unrelated contexts), and
      real-world gains associated with WM and PS training in schizophrenia. METHODS:
      Eighty-three participants with schizophrenia were recruited and randomly assigned
      to computerized WM training, PS training, or a no-training control group. Outcome
      measures included WM, PS, fluid intelligence, executive functioning, social
      cognition, and daily functioning and symptoms. RESULTS: PS training led to
      significant gains in untrained PS tasks, as well as gains in far-transfer tasks
      that required speed of processing. WM training did not lead to gains in untrained
      WM tasks and showed inconsistent effects on some far-transfer tasks. CONCLUSIONS:
      These results suggest some benefit of domain-specific cognitive training,
      specifically PS training, in schizophrenia. Far-transfer of gains to other
      cognitive domains and to real-world functioning may not occur after targeted WM
      or PS training, though non-specific effects (e.g. through behavioral activation,
      increased motivation) may lead to improvements in some tasks. Future studies
      should continue to investigate the mechanisms by which cognitive training may
      enhance cognition and functioning in schizophrenia.

PMID- 30278854
TI  - An fMRI study of multimodal selective attention in schizophrenia - CORRIGENDUM.

PMID- 30278856
TI  - Longitudinal Changes in Resting State Connectivity and White Matter Integrity in
      Adolescents With Sports-Related Concussion - Erratum.

PMID- 30278857
TI  - Executive Functions and their Relation to Sleep following Mild Traumatic Brain
      Injury in Preschoolers - Erratum.

PMID- 30278858
TI  - Change in Cognitive Performance From Midlife Into Old Age: Findings from the
      Midlife in the United States (MIDUS) Study - Erratum.

PMID- 30278855
TI  - Increasing Inaccuracy of Self-Reported Subjective Cognitive Complaints Over 24
      Months in Empirically Derived Subtypes of Mild Cognitive Impairment.
AB  - OBJECTIVES: Although subjective cognitive complaints (SCC) are an integral
      component of the diagnostic criteria for mild cognitive impairment (MCI),
      previous findings indicate they may not accurately reflect cognitive ability.
      Within the Alzheimer's Disease Neuroimaging Initiative, we investigated
      longitudinal change in the discrepancy between self- and informant-reported SCC
      across empirically derived subtypes of MCI and normal control (NC) participants.
      METHODS: Data were obtained for 353 MCI participants and 122 "robust" NC
      participants. Participants were classified into three subtypes at baseline via
      cluster analysis: amnestic MCI, mixed MCI, and cluster-derived normal (CDN), a
      presumptive false-positive group who performed within normal limits on
      neuropsychological testing. SCC at baseline and two annual follow-up visits were
      assessed via the Everyday Cognition Questionnaire (ECog), and discrepancy scores
      between self- and informant-report were calculated. Analysis of change was
      conducted using analysis of covariance. RESULTS: The amnestic and mixed MCI
      subtypes demonstrated increasing ECog discrepancy scores over time. This was
      driven by an increase in informant-reported SCC, which corresponded to
      participants' objective cognitive decline, despite stable self-reported SCC.
      Increasing unawareness was associated with cerebrospinal fluid Alzheimer's
      disease biomarker positivity and progression to Alzheimer's disease. In contrast,
      CDN and NC groups over-reported cognitive difficulty and demonstrated normal
      cognition at all time points. CONCLUSIONS: MCI participants' discrepancy scores
      indicate progressive underappreciation of their evolving cognitive deficits.
      Consistent over-reporting in the CDN and NC groups despite normal objective
      cognition suggests that self-reported SCC do not predict impending cognitive
      decline. Results demonstrate that self-reported SCC become increasingly
      misleading as objective cognitive impairment becomes more pronounced. (JINS,
      2018, 24, 842-853).

PMID- 30278859
TI  - Self-Reference Effect and Self-Reference Recollection Effect for Trait Adjectives
      in Amnestic Mild Cognitive Impairment - Erratum.

PMID- 30278861
TI  - Australian general practitioners' perspective on the role of the workplace Return
      to-Work Coordinator.
AB  - General practitioners (GPs) play a key role in the return-to-work process, and
      yet their experiences working with workplace Return-to-Work Coordinators (RTWCs)
      have rarely been studied. The aim of this paper is to provide insights from the
      GP perspective about their experiences with workplace RTWCs and their
      preparedness for the role. GPs from Australian states and territories where
      legislation mandates workplaces employ a RTWC were requested to complete a
      questionnaire on their experiences with workplace RTWCs. Fifty GPs completed a
      questionnaire on the preparedness of RTWCs in relation to their role, with 58%
      (n=29) indicating RTWCs require more training. A total of 78% (n=39) of
      respondents considered RTWCs were important in assisting injured workers return
      to work, with 98% (n=49) ranking trustworthiness, respectfulness and ethicalness
      as the most important or an important trait for a RTWC to possess. Interestingly,
      40% (n=20) of respondents themselves reported having no training in the return-to
      work process. GPs acknowledge the importance of the workplace RTWC in the return
      to-work process, and the results highlight the need for RTWCs to possess specific
      traits and undergo appropriate training for the facilitation of a successful
      return to work for injured workers.

PMID- 30278860
TI  - Identification of Carboxylesterase, Butyrylcholinesterase, Acetylcholinesterase,
      Paraoxonase, and Albumin Pseudoesterase in Guinea Pig Plasma through
      Nondenaturing Gel Electrophoresis.
AB  - Drugs to protect against nerve agent toxicity are tested in animals. The current
      preferred small animal model is guinea pigs because their plasma bioscavenging
      capacity resembles that of NHP. We stained nondenaturing polyacrylamide slab gels
      with a variety of substrates, inhibitors, and antibodies to identify the
      esterases in heparinized guinea pig plasma. An intense band of carboxylesterase
      activity migrated behind albumin. Minor carboxylesterase bands were revealed
      after background activity from paraoxonase was inhibited by using EDTA. The major
      butyrylcholinesterase band was a disulfide-linked dimer. Incubation with the
      antihuman butyrylcholinesterase antibody B2 18-5 shifted the
      butyrylcholinesterase dimer band to slower migrating complexes. Carboxylesterases
      were distinguished from butyrylcholinesterase by their sensitivity to inhibition
      by bis-p-nitrophenyl phosphate. Acetylcholinesterase tetramers formed a complex
      with the antihuman acetylcholinesterase antibody HR2. Organophosphorus toxicants
      including cresyl saligenin phosphate, dichlorvos, and chlorpyrifos oxon
      irreversibly inhibited the serine esterases but not paraoxonase. Albumin
      pseudoesterase activity was seen in gels stained with alpha- or beta-naphthyl
      acetate and fast blue RR. We conclude that guinea pig plasma has 2 types of
      carboxylesterase, butyrylcholinesterase dimers and 5 minor butyrylcholinesterase
      forms, a small amount of acetylcholinesterase tetramers, paraoxonase, and albumin
      pseudoesterase activity. A knockout mouse with no carboxylesterase activity in
      plasma is available and may prove to be a better model for studies of nerve agent
      toxicology than guinea pigs.

PMID- 30278862
TI  - Catching up with catch-up: a policy analysis of immunisation for refugees and
      asylum seekers in Victoria.
AB  - This study examines catch-up immunisation for people of refugee-like background
      in Victoria, exploring effective models of service delivery to complete catch-up
      vaccinations. The analysis is based on: (i) review of the medical literature,
      Commonwealth and Victorian government immunisation policy and immunisation
      patient information; (ii) review of vaccination coverage and service delivery
      data; and (iii) stakeholder interviews completed in 2014 with 45 people from 34
      agencies, including 9 local government areas in Victoria. Although refugees and
      asylum seekers all need catch-up vaccinations on arrival, they face significant
      barriers to completing immunisation in Australia. Analysis suggests missed
      opportunities by service providers and perceptions that catch-up vaccination is
      time-consuming, difficult and resource-intensive. Service delivery is fragmented
      across primary care and local government, and pathways depend on age, location
      and healthcare access. There are strengths, but also limitations in all current
      service delivery models. Gaps in vaccine funding for refugee-like populations
      have now been addressed through Commonwealth initiatives, however migration is
      still not well considered in immunisation policy, and existing systems for
      notification payments do not capture catch-up vaccination for these groups.
      Providers identify areas for improvement in professional development and support,
      patient information, patient-held records and immunisation surveillance data.

PMID- 30278863
TI  - Acknowledging Those Who Have Contributed Significantly to Our Profession: The
      Academy Honors.

PMID- 30278864
TI  - The Effect of Increased Cognitive Demand on Auditory Processing Assessment.
AB  - BACKGROUND: Auditory processing (AP) is commonly regarded as the perceptual
      processing of auditory information in the central nervous system. However, the
      degree to which higher level cognitive processes are involved in AP or its
      disorders is contentious. Furthermore, there is little evidence regarding the
      effects of nonauditory cognitive processes on the various tests of AP in common
      clinical usage and thus on clinical diagnoses of auditory processing disorder.
      PURPOSE: To determine the effects of increased cognitive demand, generated by
      using a dual-task paradigm, on performance on different AP tests and types of AP
      tests in common clinical usage. In addition, to investigate the relationship
      between executive function and changes in AP test performance associated with
      increased cognitive demand. RESEARCH DESIGN: Counterbalanced repeated measures
      design, with assessment of AP test performance both on its own and in a dual-task
      paradigm designed to increase cognitive demand. STUDY SAMPLE: Twenty-nine young
      adults, with no reported hearing, learning, language or attention difficulties,
      English as first language, and hearing and middle-ear status within normal
      limits. DATA COLLECTION AND ANALYSIS: Testing was completed within a single 90
      min session. A selection of standard AP tests, representing both adaptive and
      nonadaptive tests, as well as tests employing difference scores, was
      administered. These were Competing Sentences Test, Dichotic Digits Test,
      Frequency Pattern Test (nonadaptive tests); and Listening in Spatialized Noise
      Sentences test, conditions "same-voice, 0 degrees ", "different-voice, 0 degrees
      ", and "same-voice, 90 degrees " (adaptive tests), from which the difference
      scores "talker advantage" and "spatial advantage" were also derived. Each AP test
      was completed on its own (alone condition), and simultaneously with a visually
      presented task (dual-task condition). Executive function was assessed using the
      phonemic subtest of the Verbal Fluency Test. Nonparametric statistical test
      procedures were used. RESULTS: All five AP measures obtained from the nonadaptive
      tests showed a significant performance decrement in the dual-task condition
      compared with the alone condition, with one exception because of a strong ceiling
      effect. By contrast, none of the three AP measures obtained from the adaptive
      tests showed a significant performance decrement in the dual-task condition.
      Furthermore, neither of the two AP measures based on difference scores showed a
      significant performance decrement, but this finding simply reflects the lack of
      significant decrements in the relevant raw scores. Consistent with past reports
      of associations between executive function and AP performance, a significant
      positive correlation was found between executive function scores and performance
      on the Dichotic Digits Test. However, there were no significant correlations
      between executive function scores and changes in AP test scores between alone and
      dual-task conditions. CONCLUSIONS: Performance on commonly used nonadaptive tests
      of AP was significantly compromised by the increased cognitive demand resulting
      from the dual-task paradigm. By contrast, performance on AP measures obtained by
      adaptive test procedures was not significantly affected. Further investigation of
      the resilience to increased cognitive demand of the adaptive tests used here, and
      other adaptive tests of AP, is warranted. Results from this study support the
      further development of computerized adaptive tests of AP for use in clinical test
      batteries.

PMID- 30278865
TI  - Upgrade to Nucleus(r) 6 in Previous Generation CochlearTM Sound Processor
      Recipients.
AB  - BACKGROUND: The Nucleus(r) 6 sound processor is now compatible with the
      Nucleus(r) 22 (CI22M)-Cochlear's first generation cochlear implant. The Nucleus 6
      offers three new signal processing algorithms that purportedly facilitate
      improved hearing in background noise. PURPOSE: These studies were designed to
      evaluate listening performance and user satisfaction with the Nucleus 6 sound
      processor. RESEARCH DESIGN: The research design was a prospective, single
      participant, repeated measures design. STUDY SAMPLE: A group of 80 participants
      implanted with various Nucleus internal implant devices (CI22M, CI24M, Freedom(r)
      CI24RE, CI422, and CI512) were recruited from a total of six North American
      sites. DATA COLLECTION AND ANALYSIS: Participants had their external sound
      processor upgraded to the Nucleus 6 sound processor. Final speech perception
      testing in noise and subjective questionnaires were completed after four or 12
      weeks of take-home use with the Nucleus 6. RESULTS: Speech perception testing in
      noise showed significant improvement and participants reported increased
      satisfaction with the Nucleus 6. CONCLUSION: These studies demonstrated the
      benefit of the new algorithms in the Nucleus 6 over previous generations of sound
      processors.

PMID- 30278866
TI  - Using Microphone Technology to Improve Speech Perception in Noise in Children
      with Cochlear Implants.
AB  - BACKGROUND: Cochlear implant (CI) users are affected more than their normal
      hearing (NH) peers by the negative consequences of background noise on speech
      understanding. Research has shown that adult CI users can improve their speech
      recognition in challenging listening environments by using dual-microphone
      beamformers, such as adaptive directional microphones (ADMs) and wireless remote
      microphones (RMs). The suitability of these microphone technologies for use in
      children with CIs is not well-understood nor widely accepted. PURPOSE: To assess
      the benefit of ADM or RM technology on speech perception in background noise in
      children and adolescents with cochlear implants (CIs) with no previous or current
      use of ADM or RM. RESEARCH DESIGN: Mixed, repeated measures design. STUDY SAMPLE:
      Twenty (20) children, ten (10) CI users (mean age 14.3 yrs) who used Advanced
      Bionics HiRes90K implants with research Naida processors, and ten (10) NH age
      matched controls participated in this prospective study. INTERVENTION: CI users
      listened with an ear-canal level microphone, T-Mic (TM), an ADM, and a wireless
      RM at different audio-mixing ratios. Speech understanding with five microphone
      settings (TM 100%, ADM, RM + TM 50/50, RM + TM 75/25, RM 100%) was evaluated in
      quiet and in noise. DATA COLLECTION AND ANALYSIS: Speech perception ability was
      measured using children's spondee words to obtain a speech recognition threshold
      for 80% accuracy (SRT80%) in 20-talker babble where the listener sat in a sound
      booth 1 m (3.28') from the target speech (front) and noise (behind) to test five
      microphone settings (TM 100%, ADM, RM + TM 50/50, RM + TM 75/25, RM 100%). Group
      performance-intensity functions were computed for each listening condition to
      show the effects of microphone configuration with respect to signal-to-noise
      ratio (SNR). A difference score (CI Group minus NH Group) was computed to show
      the effect of microphone technology at different SNRs relative to NH. Statistical
      analysis using a repeated-measures analysis of variance evaluated the effects of
      the microphone configurations on SRT80% and performance at SNRs. Between-groups
      analysis of variance was used to compare the CI group with the NH group. RESULTS:
      The speech recognition was significantly poorer for children with CI than
      children with NH in quiet and in noise when using the TM alone. Adding the ADM or
      RM provided a significant improvement in speech recognition for the CI group over
      use of the TM alone in noise (mean dB advantage ranged from 5.8 for ADM to 16 for
      RM100). When children with CI used the RM75 or RM100 in background babble, speech
      recognition was not statistically different from the group with NH. CONCLUSION:
      Speech recognition in noise performance improved with the use of ADM and RM100 or
      RM75 over TM-only for children with CIs. Alhough children with CI remain at a
      disadvantage as compared with NH children in quiet and more favorable SNRs,
      microphone technology can enhance performance for some children with CI to match
      that of NH peers in contexts with negative SNRs.

PMID- 30278867
TI  - Accounting for the Occlusion Effect with Insert Earphones.
AB  - BACKGROUND: There are clinical implications associated with knowing when the
      occlusion effect (OE) must be accounted for during bone conduction (BC) testing
      because spurious results can occur when errors are made in this regard. The
      amount of OE produced when insert earphones (IEs) are used varies in the
      literature; thus, further investigation is warranted. PURPOSE: The purpose of
      this project was to determine the OE during BC threshold measurements under the
      following occluding conditions used clinically: when using partial insertion (PI)
      versus full insertion (FI) depth and when occluding one versus both ears.
      RESEARCH DESIGN: A descriptive within-subjects design was used in this study.
      STUDY SAMPLE: Twenty-two adults with mean four-frequency pure tone averages of 24
      dB HL, aged 40-83 yr, participated. INTERVENTION: BC thresholds were obtained at
      250, 500, and 1000 Hz under seven conditions: (1) both ears unoccluded, (2) left
      ear occluded with PI, (3) right ear occluded with PI, (4) both ears occluded with
      PI, (5) left ear occluded with FI, (6) right ear occluded with FI, (7) both ears
      occluded with FI. For PI, one half of the length of the IE was beyond the opening
      of the ear canal. For FI, the lateral edge of the foam insert was flush with the
      entrance to the ear canal. DATA COLLECTION AND ANALYSIS: Mean OEs were compared
      with previously published data. In addition, variability in the data was examined
      using frequency distribution plots as well as cumulative frequency and percentile
      values. RESULTS: Mean OEs of 5-13 dB were present in all but the FI condition at
      1000 Hz where the OE was <3 dB. Differences between PI and FI conditions were
      present at each frequency measured, irrespective of whether one or both ears were
      occluded. The shifts in threshold were consistently more prevalent and greater
      for the PI than the FI conditions overall. Mean differences between the one-ear
      and both-ears conditions were not clinically significant. Clinically significant
      variability in the data was noted, except when comparing the one-ear versus both
      ears conditions. CONCLUSIONS: Occluding the ear during initial BC measurements
      may artificially improve the thresholds and create or exaggerate an air-bone gap.
      Thus, initial BC testing should be performed unoccluded at 250, 500, and 1000 Hz.
      There is a need to account for the OE even when the IE is flush with the ear
      canal to avoid insufficient masking.

PMID- 30278868
TI  - Impact of Consistency in Daily Device Use on Speech Perception Abilities in
      Children with Cochlear Implants: Datalogging Evidence.
AB  - BACKGROUND: Cochlear implants (CIs) give children with severe to profound hearing
      loss access to sound. There appears to be a dose effect of sound exposure on
      speech perception abilities as shown by the positive influence of early
      implantation and CI experience. The consistency in device use per day could also
      affect sound dose, potentially affecting perceptual abilities in children with
      CIs. PURPOSE: The objectives of the present study were to identify the impact of
      consistency in device use on: (1) speech perception abilities and (2) asymmetry
      in speech perception abilities between bilateral CIs. RESEARCH DESIGN:
      Retrospective analysis. STUDY SAMPLE: To achieve the first objective, data from
      65 children (age range at speech test: 1.91-18.05 yrs) with one (unilaterally
      implanted or bimodal) or two CIs (sequentially or simultaneously implanted) were
      included. A subset of data from 40 children with bilateral CIs was included to
      achieve the second objective. Of the 40 children with two CIs, 15 received their
      CIs sequentially. DATA COLLECTION AND ANALYSIS: Device use information was
      extracted from datalogs stored in personal speech processors using custom
      software. Speech perception scores per CI collected in quiet were also evaluated.
      Multiple regression was used to assess the impact of daily CI use, while
      controlling for factors previously identified to affect speech perception: age at
      speech test, length of pre-CI (acoustic) hearing experience, length of CI hearing
      experience, and order of CI for the first objective, and CI category
      (simultaneous/sequential implantation), interimplant delay, and length of CI
      experience for the second objective. RESULTS: On average, children wore their CIs
      for 11.59 +/- 2.86 hours/day and, with one CI, exhibited 65.07 +/- 22.64%
      accuracy on speech perception tests. Higher monaural speech perception scores
      were associated with longer everyday CI use and CI experience (p < 0.05). Among
      children with bilateral CIs, those with simultaneously implanted CIs and similar
      bilateral hearing experience demonstrated a small but significant right ear
      advantage with higher speech perception scores when using the right rather than
      left CI (mean difference = 4.55 +/- 9.83%). The asymmetry in speech perception
      between CIs was larger and more variable in children who received their CIs
      sequentially (mean difference CI1-CI2 = 27.48 +/- 24.87%). These asymmetries
      decreased with longer/consistent everyday use of the newer CI (p < 0.05). Yet,
      despite consistent everyday device use of the second CI (>12 hours/day), only a
      small proportion of children implanted sequentially (one out of seven children)
      achieved symmetrical function similar to children with simultaneously received
      bilateral CIs. CONCLUSIONS: Consistent everyday CI use contributes to higher
      speech perception scores. Although consistent CI use can help reduce the
      asymmetry in speech perception abilities of children with sequentially implanted
      CIs subsequent to interimplant delay, residual asymmetry often persists.

PMID- 30278869
TI  - Refining Stimulus Parameters in Assessing Infant Speech Perception Using Visual
      Reinforcement Infant Speech Discrimination in Infants with and without Hearing
      Loss: Presentation Level.

PMID- 30278870
TI  - The Middle Latency Response: A Review of Findings in Various Central Nervous
      System Lesions.
AB  - BACKGROUND: The middle latency response (MLR) first came to light as an auditory
      evoked potential in 1958. Since then, it has aroused substantial interest and
      investigation by clinicians and researchers alike. In recent history, its use and
      popularity have dwindled in tandem with various other auditory evoked potentials
      in audiology. One area for which MLR research and application has been overlooked
      is its potential value in measuring the neural integrity of the auditory
      thalamocortical pathway. In a broader sense, the MLR, when combined with the
      auditory brain stem response, can provide information concerning the status of
      much of the central auditory system pathways. This review is intended to provide
      information concerning the MLR as a measure of central auditory function for the
      reader to consider. PURPOSE: To review and synthesize the scientific literature
      regarding the potential value of the MLR in assessing the integrity of the
      central auditory system and to provide the reader an informed perspective on the
      value of the MLR in this regard. Information is also provided on the MLR
      generator sites and fundamental characteristics of this evoked potential
      essential to its clinical and or research application. RESEARCH DESIGN: A
      systematic review and synthesis of the literature focusing on the MLR and lesions
      of the central auditory system. STUDY SAMPLE: Studies and individual cases were
      reviewed and analyzed that evidenced documented lesions of the central auditory
      nervous system. DATA COLLECTION AND ANALYSIS: The authors searched and reviewed
      the literature (journal articles, book chapters, and books) pertaining to central
      auditory system lesion effects on the MLR. RESULTS: Although findings varied from
      study to study, overall, the MLR was reasonably sensitive and specific to
      neurological compromise of the central auditory system. This finding is
      consistent with the generator sites of this evoked potential. CONCLUSIONS: The
      MLR is a valuable tool for assessing the integrity of the central auditory
      system. It should be of interest to the clinician or researcher who focuses their
      attention on the function and dysfunction of the higher auditory system.

PMID- 30278873
TI  - Endophthalmitis Rates After Bilateral Same-Day Intravitreal Anti-Vascular
      Endothelial Growth Factor Injections.

PMID- 30278872
TI  - Ventilator-associated pneumonia agents in Brazilian Neonatal Intensive Care Units
      - a systematic review.
AB  - INTRODUCTION: Ventilator-associated pneumonia (VAP) is one of the most common
      healthcare-associated infections (HAI) in neonates admitted in neonatal intensive
      care units (NICUs). METHODS: We did a systematic review using PRISMA methodology
      to identify the main etiological agents in Brazilian NICUs. Eligible studies
      published without period restriction were identified in PUBMED, SCIELO, LILACS
      and DOAJ. Studies were included if they were conducted in neonates hospitalized
      at NICU. Studies done in outpatient care, neonates outside NICU, emergency
      department, primary care, long-term care facilities or a combination of these
      were excluded. RESULTS: We identified 6384 articles in the initial search and
      four papers met the inclusion criteria. In all studies included, rates of device
      associated infections were described, including VAP rates. The VAP incidence
      density, in exclusively Brazilian NICU, ranged from 3.2 to 9.2 per 1000
      ventilator-days. Pneumonia was described as the main HAI in NICU in one article,
      as the second type of HAI in two other articles and as the fourth type of HAI in
      the last one. The main pathogens causing all HAI types were described in three of
      four articles, but, none of the articles reported which pathogens were related or
      associated to VAP. CONCLUSION: Etiological agents causing VAP in Brazilian NICUs
      are, until the present time, not known.

PMID- 30278874
TI  - Reply.

PMID- 30278875
TI  - Hemophagocytic Lymphohistiocytosis in the Elderly.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare disease of massive,
      dysregulated cytokine release and secondary multiorgan failure and is associated
      with high mortality. Primary HLH occurs predominately in infants and young
      children with a genetic predisposition. Acquired HLH is less well characterized
      and usually occurs in younger adults in the setting of severe inflammation
      triggered by infection or malignancy. Little is known about the disease in
      elderly. We report 3 patients >50 years old who presented with multiorgan failure
      and shock without an identifiable source and were ultimately diagnosed with
      acquired HLH. We performed a literature review of HLH in adults >50 years of age
      and identified an additional 68 cases. Mean age was 62 years, with male
      predominance. Most cases were triggered by infection (49%) followed by malignancy
      (27%). Nineteen patients were treated with the HLH-94 protocol, 11 received
      corticosteroids and the remainder received non-HLH specific interventions.
      Overall mortality was 62%.

PMID- 30278876
TI  - Broadening the Differential Diagnosis of IgG4-related Pleuritis.

PMID- 30278877
TI  - Honiton Laces in Oral Cavity.

PMID- 30278878
TI  - A Patient-Centered Approach to Care and Research in Chronic Disease.

PMID- 30278879
TI  - Implementation and validation of a retroperitoneal dissection curriculum.
AB  - BACKGROUND: Competency-based education requires educators to use simulation
      training for the purposes of education and assessment of resident trainees.
      Research demonstrates that improvement in surgical skills acquired in a simulated
      environment is transferrable to the operative environment. Laparoscopic
      retroperitoneal dissection, opening the retroperitoneal space and identifying the
      ureter, is a fundamental skill for gynecologists. Integrating simulation models
      into a formal and comprehensive curriculum for teaching ureterolysis could
      translate to increased surgical competency. OBJECTIVE: Our goal was to validate a
      comprehensive curriculum for laparoscopic retroperitoneal dissection for the
      purpose of identification of the ureter by evaluating intraoperative performance.
      STUDY DESIGN: A comprehensive curriculum, encompassing didactic and technical
      skills components and using a previously developed pelvic model, was designed to
      teach laparoscopic ureterolysis. Novice surgeons (postgraduate years 3-5) were
      recruited. Participants completed precurriculum and postcurriculum multiple
      choice questionnaires to evaluate a didactic component. Preperformance and
      postperformance on the model was video-recorded. As part of the technical
      component, participants received constructive feedback from expert surgeons on
      how to perform laparoscopic retroperitoneal dissection using the simulation
      model. Participants were then video-recorded performing laparoscopic
      retroperitoneal dissection in the operating room within 3 months of the
      curriculum. All videos were blindly assessed by an expert using the Objective
      Structured Assessment of Technical Skills tool. At the conclusion of the study,
      participants completed a course evaluation. RESULTS: Thirty novice gynecologic
      surgeons were recruited. High baseline knowledge of ureteric anatomy and injury
      (multiple-choice question score median and interquartile range) still
      significantly increased from 7 (5-7.25) precurriculum to 8 (7-9) postcurriculum
      (P < .001). The median (interquartile range) technical Objective Structured
      Assessment of Technical Skills score increased significantly from 24.5 (23-28.25)
      precurriculum to 30 (29.75-32) postcurriculum (P < .001). Video-recordings were
      completed for 23 participants performing laparoscopic retroperitoneal dissection
      in the operating room. Intraoperative Objective Structured Assessment of
      Technical Skills scores (median of 29 [interquartile range 27-32]) correlated
      with postcurriculum Objective Structured Assessment of Technical Skills scores on
      the model (r = 0.53, P = .01). The ureter was identified intraoperatively by 91%
      (n = 21/23) of participants. The majority of residents (81%, n = 21/26) were more
      comfortable completing a supervised retroperitoneal dissection as a result of
      participating in the curriculum. Residents believed that this model would be
      useful to enhance skills acquisition prior to performing the skill in the
      operating room (65%, n = 17/26). CONCLUSION: A comprehensive retroperitoneal
      dissection curriculum showed improvement in cognitive knowledge and technical
      skills, which also translated to competent performance in the operating room. In
      addition to the objective measures, residents believed that their skills
      acquisition was improved following course completion.

PMID- 30278880
TI  - The emergency surgical airway: Bridging the gap from quality outcome to
      performance improvement through a novel simulation based curriculum.
AB  - BACKGROUND: Emergency surgical airway is a low frequency, high risk clinical
      scenario. Implementing a simulation-based curriculum may bridge the gap in
      surgical training and address quality assurance/performance improvement (QAPI)
      needs. METHODS: We designed and implemented an Advanced Surgical Airway
      Curriculum (ASAC) modeled after proficiency-based training. General Surgery
      residents and student nurse anesthetists were enrolled. Evaluation consisted of
      cognitive tests, procedure checklists and questionnaire. RESULTS: In total, 78
      participants successfully completed the ASAC. Trainees agreed that the curriculum
      provided the cognitive and psychomotor skills necessary to perform both an open
      and needle cricothyroidotomy. CONCLUSIONS: In the age of increased patient safety
      concerns, QAPI initiatives can serve as a driver for simulation-based training
      curricula, with particular focus on individualized, active learning. This may be
      particularly useful in high risk, low frequency scenarios in which the
      traditional method of "See one, Do one, Teach one," is not feasible.

PMID- 30278882
TI  - Brugada syndrome: Keep an eye on the electrocardiogram.

PMID- 30278883
TI  - [DNA damage repair: An emerging strategy in metastatic prostate cancer].
AB  - Genetic instability is one part of the oncogenic process. Gene mutations involved
      in DNA repair mechanisms can promote this genetic instability and participate in
      oncogenesis and metastatic progression. In prostate cancer, DNA repair
      abnormalities mainly correspond to somatic or constitutional mutations of the
      BRCA2 and ATM genes. Therapeutic management of metastatic castration-resistant
      prostate cancer (mCRPC) is currently based on new hormonal therapies
      (abiraterone, enzalutamide) and taxane-type chemotherapy (docetaxel or
      cabazitaxel). Preliminary data tend to indicate a specific activity of agents
      causing DNA breaks (platinum salts) and PARP inhibitors in patients with these
      DNA repair abnormalities. The frequency of DNA repair gene mutations in patients
      with prostate cancer (around 20%) and the antitumor response of PARP inhibitors
      make it a possible short-term therapeutic strategy with several registering
      clinical trials ongoing.

PMID- 30278884
TI  - Long noncoding RNA LOXL1-AS1 regulates prostate cancer cell proliferation and
      cell cycle progression through miR-541-3p and CCND1.
AB  - Prostate cancer is one of the most frequent malignancies affecting men. Long non
      coding RNAs (lncRNAs) are involved in the pathogenesis of prostate cancer. LncRNA
      LOXL1-AS1 participates in the pathogenesis of the exfoliation syndrome. However,
      the role of LOXL1-AS1 in cancer remains largely unknown. Here, we found that
      LOXL1-AS1 down-regulation inhibited prostate cancer cell proliferation and cell
      cycle progression. RNA sequencing analysis revealed that it regulates the
      expression of cell cycle-related genes. LOXL1-AS1 is predominantly distributed in
      the cytoplasm, where it interacts with miR-541-3p. In addition, miR-541-3p
      targets the cell cycle regulator CCND1 in prostate cancer cells. LOXL1-AS1 down
      regulation inhibits the expression of CCND1 and cell cycle progression, whereas
      these effects are abolished upon miR-541-3p suppression. In summary, our study
      revealed that LOXL1-AS1 regulates prostate cancer cell proliferation and cell
      cycle progression through miR-541-3p and CCND1. Modulation of their levels may be
      used to treat prostate cancer.

PMID- 30278885
TI  - BAF53A regulates androgen receptor-mediated gene expression and proliferation in
      LNCaP cells.
AB  - The actin-like protein of the SWI/SNF complex, BAF53A, regulates gene expression
      by the gene-specific chromatin remodeling of target genes. However, the function
      of BAF53A in the androgen receptor pathway in prostate cancer cells remains
      unclear. Here, we demonstrated that BAF53A positively regulates the expression of
      endogenous AR target genes (e.g. PSA, TMPRSS2, FKBP5, and KLK2) in LNCaP cells.
      It functions as a coactivator in AR-mediated transcription by interacting with
      other nuclear receptor coactivators, such as p300 and FLII, and is associated
      with AR in the presence of dihydrotestosterone (DHT). The DHT-induced recruitment
      of BAF53A to the proximal and distal androgen response elements (AREs) of the PSA
      gene in the presence of BRG1 (but not BRM) was inhibited by an AR antagonist,
      suggesting the coactivator function of BAF53A in the SWI/SNF complex. Depletion
      of BAF53A in LNCaP cells resulted in a significant decrease in growth rate.
      Furthermore, the expression of BAF53A in prostate cancer tissue was significantly
      elevated, compared to that in normal prostate tissue, and correlated with the
      expression of AR, and BRG1, but not BRM. Therefore, our results suggested that
      BAF53A plays an important role in the expression of AR target genes in prostate
      cancer, and can be used clinically for the treatment of prostate cancer.

PMID- 30278886
TI  - Selective toxicity of caffeic acid in hepatocellular carcinoma cells.
AB  - Caffeic acid is a natural phytochemical structurally similar to other cinnamic
      acids. In this study we found caffeic acid (CA) but not ferulic, sinapic or
      cinnamic acids inhibited proliferation of hepatocellular carcinoma cells (HCC)
      and reduced cell numbers by inducing apoptosis. Only transient exposure to CA was
      required for these lethal effects that are associated with disruption of
      mitochondrial membrane potential and induction of reactive oxygen species. By
      comparison, primary hepatocytes resisted CA toxicity for nearly 48 h, consistent
      with selective sensitivity of HCC to CA. These results support use of CA as an
      anti-tumor agent to inhibit HCC, especially if delivered by locoregional
      catheterization in an embolization procedure.

PMID- 30278887
TI  - Ferricrocin, the intracellular siderophore of Trichoderma virens, is involved in
      growth, conidiation, gliotoxin biosynthesis and induction of systemic resistance
      in maize.
AB  - Fungal siderophores are known to be involved in iron acquisition and storage, as
      well as pathogenicity of mammals and plants. As avirulent plant symbionts,
      Trichoderma spp. colonize roots and induce resistance responses both locally and
      systemically. To study the role of intracellular siderophore(s) in Trichoderma
      plant interactions, we have obtained mutants in a non-ribosomal peptide
      synthetase, TvTex10, that was predicted to be involved in intracellular
      siderophore(s) biosynthesis. This gene has a detectable basal level of expression
      and is also upregulated under iron-deplete conditions. This is unlike two other
      siderophore-encoding genes, which are tightly regulated by iron. Disruption of
      tex10 gene using homologous recombination resulted in mutants with enhanced
      growth rate, reduced conidiation and hyper-sensitivity to oxidative stress as
      compared to wildtype strain. The mutants also produced reduced levels of
      gliotoxin and dimethyl gliotoxin but have enhanced ability to colonize maize
      seedling roots. The mutants were also impaired in induction of induced systemic
      resistance (ISR) in maize against the foliar pathogen Cochliobolus
      heterostrophus.

PMID- 30278888
TI  - Maternal supplementation with calcium varying with feeding time daily during late
      pregnancy affects lipid metabolism and transport of placenta in pigs.
AB  - To investigate effects of Ca level varying with feeding time daily in sows during
      late pregnancy on placental lipid metabolism and transport in pigs, sixty
      pregnant sows were assigned to 3 groups: the CON group was fed low-Ca diet with
      11.25 g CaCO3 at 0600 h and 1500 h, H-L group was fed low-Ca diet with 22.5 g
      CaCO3 at 0600 h and low-Ca diet at 1500 h, and L-H group was fed low-Ca diet at
      0600 h and low-Ca diet with 22.5 g CaCO3 at 1500 h, respectively. Serum from sows
      and umbilical cord and placenta were collected during delivery. Results showed
      that, compared with the CON group, H-L feeding significantly increased maternal
      serum total triglyceride (TG) and umbilical serum high-density lipoprotein (HDL)
      (P < 0.05). The results showed that long chain fatty acid (FA) contents in
      placenta were significantly increased in H-L and L-H groups (P < 0.05).
      Experiments on genes involved in glycolipid metabolism showed that H-L or L-H
      feeding inhibited mRNA expression of GLUT3, GLUT4, FAS, FABP1, FABPpm, FAT/CD36,
      while activated the mRNA expression of FASD1, FASD2 and SCD in placenta (P <
      0.05). In addition, experiments on genes involved in biological clock showed that
      L-H feeding sequence activated the mRNA expression of per1 and clock, while H-L
      and L-H feeding sequence inhibited mRNA expression of per2 in placenta (P <
      0.05). It is concluded that maternal supplementation with Ca varying with feeding
      time daily during late pregnancy affects placental lipid metabolism and transport
      in pigs by regulating the mRNA expression related to lipid metabolism and the
      circadian clock.

PMID- 30278889
TI  - Natural deep eutectic solvents-mediated extractions: The way forward for
      sustainable analytical developments.
AB  - The concept of sustainable development has impacted in analytical chemistry
      changing the way of thinking processes and methods. It is important for
      analytical chemists to consider how sample preparation can integrate the basic
      concepts of Green Chemistry. In this sense, the replacement of traditional
      organic solvents is of utmost importance. Natural Deep Eutectic Solvents (NADES)
      have come to light as a green alternative. In the last few years, a growing
      number of contributions have applied these natural solvents proving their
      efficiency in terms of extraction ability, analyte stabilization capacity and
      detection compatibility. However, the arising question that has to be answered
      is: the use of NADES is enough to green an extraction process? This review
      presents an overview of knowledge regarding sustainability of NADES-based
      extraction procedures, focused on reported literature within the timeframe
      spanning from 2011 up to date. The contributions were analyzed from a green
      perspective in terms of energy, time, sample and solvent consumption. Moreover,
      we include a critical analysis to clarify whether the use of NADES as extraction
      media is enough for greening an analytical methodology; strategies to make them
      even greener are also presented. Finally, recent trends and future perspectives
      on how NADES-based extraction approaches in combination with computational
      methodologies can contribute are discussed.

PMID- 30278890
TI  - Sensitive DNA detection by polymerase chain reaction with gold nanoparticles.
AB  - We developed a novel strategy for rapid colorimetric detection of specific DNA
      sequence based on gold nanoparticles assemblies induced by polymerase chain
      reaction (PCR) product. In the presence of target DNA, the two DNA-functionalized
      AuNP probes selectively hybridized with the prohibited nucleic acid segments of
      two primers owing to the zipping off of the hairpin structures during PCR
      process, resulted in the aggregation of AuNPs with a concomitant color change
      from red to blue-purple. It is a convenient and universal method for sensitive
      DNA detection with no need for any further post-treatment of the PCR products.
      Most importantly, our method showed a low limit of detection (LOD) of 4.3 fM with
      a wide range of target DNA from 16 fM to 1.6 nM. Owing to the versatility and low
      cost, the proposed strategy could be extremely useful for a wide range of
      applications, providing a promising tool for rapid disease diagnostics and gene
      sequencing.

PMID- 30278891
TI  - A novel enzyme-free glucose and H2O2 sensor based on 3D graphene aerogels
      decorated with Ni3N nanoparticles.
AB  - In this work, a novel enzyme-free glucose and hydrogen peroxide (H2O2) sensor
      based on Ni3N nanoparticles on conductive 3D graphene aerogels (Ni3N/GA) has been
      successfully synthesized by using hydrothermal reaction, freeze-dried and then
      calcined under NH3 atmosphere. The obtained Ni3N/GA composites were characterized
      by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), nitrogen
      adsorption-desorption isotherms and electrochemical methods. The results show the
      obtained 3D Ni3N/GA composites exhibit excellent electrochemical performance
      toward glucose oxidation and H2O2 reduction with larger catalytic rate constant
      Kcat value of 3.75 * 103 M-1 s -1 and 1.24 * 103 M-1 s -1, respectively. As a
      glucose sensor, the obtained electrode provides a wide detection range of 0.1
      7645.3 MUM, fast response time within 3 s, high sensitivity of 905.6 MUA mM-1 cm
      2 and low detection limit of 0.04 MUM. For detection of H2O2, this prepared
      sensor offers a wide detection range (5 MUM-75.13 mM), fast response time (within
      5 s), sensitivity (101.9 MUA mM-1 cm-2) and low detection limit (1.80 MUM). This
      enzyme-free glucose and H2O2 sensor display satisfactory selectivity,
      reproducibility and long-term storage stability. Additionally, the sensor can
      also be used for glucose and H2O2 detection in human blood serum. The results
      demonstrate that 3D GA nanostructures provide an enviable conductive network for
      efficient charge transfer and avoid Ni3N nanoparticles aggregation, which is
      advantageous for electrocatalytic applications.

PMID- 30278892
TI  - Dual-mode fluorescent and colorimetric immunoassay for the ultrasensitive
      detection of alpha-fetoprotein in serum samples.
AB  - We present a novel dual-mode fluorescent and colorimetric immunosensor based on
      conventional immunoassay platforms by utilizing a gold nanoflower (AuNF)-loaded
      fluorescein molecule (AuNF@Fluorescein) as signal output. The AuNFs were modified
      with thiolated carboxyl ligand, which consisted of a hydrophobic alkane chain as
      hydrophobic wallet for fluorescein encapsulation, a tetra (ethylene glycol) unit
      for biocompatibility and solubility, and a functional carboxyl group for the
      conjugation of biorecognition molecules for biosensing. The resultant AuNFs
      showed a high loading capacity of 3.74 * 106 fluorescein molecules per AuNF
      because of its flower-like shape with many complex branches. By adjusting the
      solution pH to 8.0, the fluorescein molecules can almost entirely be released
      from the hydrophobic wallet of AuNF@Fluorescein, which led to strong fluorescent
      signal amplification. Under the optimal detection conditions, the proposed
      immunoassay based on fluorescent signal exhibited ultrahigh sensitivity for alpha
      fetoprotein (AFP) detection, with a limit of detection (LOD) of 29 fg/mL. This
      value is approximately 9.3 * 103-fold lower than that of corresponding
      horseradish peroxidase (HRP)-based immunoassay (LOD = 270 pg/mL). The fluorescein
      molecule also had intrinsic peroxidase-like activity to catalyze 3,3',5,5'
      tetramethylbenzidine oxidation with hydrogen peroxide for colorimetric signal.
      The proposed method with colorimetric mode further exhibited a sensitivity with a
      LOD of 17.7 pg/mL, which is about 15-fold lower than that of conventional HRP
      based immunoassay. The recoveries of the proposed dual-mode immunoassay for AFP
      spiked serum samples ranged within 89.85%-100.0%, with the coefficient of
      variations ranging from 0.5% to 2.4%, indicating acceptable accuracy and
      precision for AFP quantitative detection. The reliability of the developed dual
      mode immunoassay was further compared with a commercial chemiluminescence
      immunoassay kit by analyzing 20 clinical serum samples, showing that the two
      methods well agreed with each other, with high correlation coefficients of 0.997
      and 0.986 based on recorded fluorescence and colorimetric signals, respectively.
      In summary, the proposed method was highly suitable for the ultrasensitive
      analysis of biomarkers or infectious diseases by fluorescence mode and can be
      used for routine clinical diagnosis by colorimetric mode.

PMID- 30278893
TI  - A simple and sensitive fluorescence method for detection of telomerase activity
      using fusion protein bouquets.
AB  - Telomerase is considered as a widely accepted cancer biomarker for early cancer
      diagnostics. Herein, we develop a simple, ultrahigh sensitivity method for
      detection of telomerase activity, which relied on that RecA-GFP fusion proteins
      wrapped around telomeric DNA to form fluorescence bouquets. RecA-GFP fusion
      protein was synthesized through fusion protein technology. In the presence of
      telomerase, telomerase elongation products are wrapped around by RecA-GFP fusion
      protein to form big fluorescent bouquets, which resulted in strong fluorescence.
      This method has the linear range from 50 to 1000 HeLa cells and the detection
      limit is 8 HeLa cells, based on a signal-to-noise ratio (S/N) of 3. Compared with
      conventional methods, this method has the advantages of low toxicity, outstanding
      sensitivity, and excellent selectivity. Hence, it provides a promising approach
      for the detection of telomerase activity and diagnosis of cancer.

PMID- 30278894
TI  - Aptamer proximity recognition-dependent strand translocation for enzyme-free and
      amplified fluorescent detection of thrombin via catalytic hairpin assembly.
AB  - By coupling a new aptamer proximity recognition-dependent strand translocation
      strategy with catalytic hairpin assembly (CHA) signal amplification, we have
      developed a simple and sensitive method for detecting thrombin in human serums.
      Simultaneous binding of two engineered aptamer probes to the thrombin target
      significantly increases the local concentrations of the two probes and
      facilitates the translocation of a ssDNA strand from one of the probes to the
      other through toehold mediated strand displacement. Such a strand translocation
      leads to the generation of a ssDNA tail in the aptamer sequence for subsequent
      initiation of the assembly of two fluorescently quenched hairpins into many DNA
      duplexes via CHA. The formation of the DNA duplexes thus results in significant
      fluorescence recovery for amplified detection of thrombin down to 8.3 pM. The
      developed method is highly selective to the thrombin target against other
      interference proteins due to the dual recognition mode, and can be employed to
      monitor thrombin in human serum samples. With the advantage of simplicity,
      sensitivity and selectivity, this method can be a universal non-enzymatic and
      nanomaterial-free amplified sensing platform for detecting different protein
      molecules.

PMID- 30278895
TI  - Fabricating carbon-nanotubes-based porous foam for superoxide electrochemical
      sensing through one-step hydrothermal process induced by phytic acid.
AB  - The detection of superoxide anions (O2*-) is widely considered as a potential way
      for cancer diagnosis and the development of enzyme-mimic catalysts is the main
      challenge in the establishment of electrochemical sensors for O2*- sensing in
      real samples. Here we present a novel enzyme- and metal-free electrochemical
      catalyst for superoxide (O2*-) sensing based on the widely-used carbon nanotubes
      (CNT). Through a one-step hydrothermal process induced by phytic acid (PA), CNT
      based porous foam (PACNTF) was successfully obtained. Characterizations
      demonstrated the enhanced defect and disorder degree of PACNTF after PA
      treatment, which leaded to the increased active sites of PACNTF for electron
      transfer and the adhesion of O2*- during the electrochemical process. As a
      result, the PACNTF presented higher conductivity and larger current response
      toward O2*- sensing when compared with CNT precursor and CNTF without PA
      treatment. The sensitivity of PACNTF/SPCE was calculated to be 1230 MUA cm-2 mM-1
      in the linear range of 0-193.6 MUM (R2 = 0.965) and 373 MUA cm-2 mM-1 in the
      linear range of 193.6-1153.6 MUM (R2 = 0.995) with a limit of detection of 0.16
      MUM (S/N = 3). Further, the PACNTF/SPCE presented fast response toward cell
      released O2*- stimulated by Zymosan A. The above results indicated that the
      fabricated sensor holds potential usage in biological samples.

PMID- 30278896
TI  - Hairpin-structured probe conjugated nano-graphene oxide for the cellular
      detection of connective tissue growth factor mRNA.
AB  - Identification of abnormal scars at their early stage has attracted increasing
      attentions as the scars can only be assessed qualitatively and subjectively upon
      maturity, when no invasive procedure is involved. This report introduces a
      fluorescent probe that targets a potential abnormal scar biomarker (connective
      tissue growth factor (CTGF) mRNA) in skin fibroblasts. This probe is constructed
      of hairpin-structured probes (HPs) targeting CTGF mRNA and the nano-graphene
      oxide (nano-GO) base. The HPs are non-covalently absorbed on the surface of nano
      GO, which pre-quenches the fluorescence of HPs. Close proximity of complementary
      CTGF mRNA would lead to preferential HP hybridization and dissociation from nano
      GO, which restores the fluorescence signal from HPs. Utilizing this probe, we can
      distinguish abnormal fibroblasts derived from abnormal scars and assess the
      effectiveness of anti-scarring drugs like Repsox and transforming growth factor
      beta type I receptor (TGF-betaRI) siRNA.

PMID- 30278897
TI  - Fluorescent/SERS dual-sensing and imaging of intracellular Zn2.
AB  - A fluorescent and surface-enhanced Raman spectroscopy (SERS) dual-mode probe is
      developed for imaging of intracellular Zn2+ based on N-(2-(bis(pyridine-2
      ylmethyl)amino)ethyl)-2-mercaptoacetamide (MDPA) modified gold nanoparticles
      (MDPA-GNPs). Benefiting from the chelation-enhanced fluorescence (CHEF) between
      MDPA-GNPs and Zn2+, the fluorescent intensities of MDPA-GNPs are substantially
      enhanced with the increment of Zn2+ concentrations, which can be clearly observed
      by the naked eye. Under physiological conditions, the probe exhibits a stable
      response for Zn2+ from 1 MUM to 120 MUM, with a detection limit of 0.32 MUM in
      aqueous solutions. The resultant MDPA-GNPs can be used for ultrasensitive SERS
      detection of Zn2+ because of the strong inter-particle plasmonic coupling
      generated in the process of Zn2+-triggered MDPA-GNPs self-aggregation, with a low
      detection limit of 0.28 pM, which is eight order of magnitude lower than the
      United States Environmental Protection Agency (US EPA)-defined limit (76 MUM) in
      drinkable water. More importantly, the proposed probe can be applied for
      efficient detection of intracellular Zn2+ with excellent biocompatibility and
      cellular imaging capability. Therefore, a highly sensitive and selective
      nanosensor has been demonstrated for both reliable quantitative detection of Zn2+
      in aqueous solution and real-time imaging of intracellular Zn2+, suggesting its
      significant potential utility in bioanalysis and biomedical detection in the
      future.

PMID- 30278898
TI  - Fluorescence enhancement of silver nanocluster at intrastrand of a 12C-loop in
      presence of methylated region of sept 9 promoter.
AB  - Determining methylation state of a particular DNA sequence is an essential task
      in many epigenetic investigations. Here a facile method based on silver
      nanocluster (AgNCs) fluorescence enhancement is presented. Target sequences were
      selected from Sept9 promoter region that its hypermethylation is demonstrated as
      a reliable biomarker of colorectal cancer. Probe DNA was complementary to a 25
      nucleotide of the target region and possessed twelve additional cytosines in the
      middle to grant the formation of AgNCs. After probe strands were hybridized with
      methylated and non-methylated targets separately, AgNCs were synthesized, and
      their fluorescence intensities were recorded. Fluorescence intensity enhanced
      when the target strands were methylated and quenched when they were non
      methylated. The Linear range of fluorescence enhancement was from 1.0 * 10-7 M to
      5.0 * 10-7 M with the detection limit of 7.6 * 10-8 M. Sensor specificity was
      checked with non-complementary strands with the maximum similarity of 40%.
      Further experiments explored various characteristics of methylated and non
      methylated DNAs carrying AgNC and indicated that structure of methylated and non
      methylated DNAs was affected differently by silver ions that could then influence
      AgNC fluorescence. This effect was strongly sequence-dependent, and either
      fluorescence enhancement or quenching was observed with two different sequences.

PMID- 30278899
TI  - Electrochemical screening of single nucleotide polymorphisms with significantly
      enhanced discrimination factor by an amplified ratiometric sensor.
AB  - The detection of single nucleotide polymorphisms (SNPs) is of great clinical
      significance to the diagnosis of various genetic diseases and cancers. In this
      work, the development of an ultrasensitive ratiometric electrochemical sensor for
      screening SNP with a significantly enhanced discrimination factor is reported.
      The ferrocene (Fc) and methylene blue (MB) dual-tagged triple helix complex (THC)
      probes are self-assembled on the gold electrode to construct the sensing
      interface. The addition of the mutant p53 gene causes the disassembly of the THC
      probes with the release of the Fc-tagged sequence and the folding of the MB
      labeled sequence into a hairpin structure, causing the change in the current
      response ratio of MB to Fc for monitoring the mutant p53 gene. Such ratio is
      dramatically enhanced by the toehold-mediated displacement reaction-assisted
      target recycling amplification with the presence of an assistance hairpin
      sequence. With the significant signal amplification and the advantageous
      specificity of the THC probes, sub-femtomolar detection limit and a highly
      enhanced SNP discrimination factor for the mutant p53 gene can be obtained.
      Besides, the proof-of-demonstration application of the sensor for diluted real
      samples has been verified, offering such sensor new opportunities for monitoring
      various genetic related diseases.

PMID- 30278900
TI  - Non-SELEX isolation of DNA aptamers for the homogeneous-phase fluorescence
      anisotropy sensing of tau Proteins.
AB  - Herein, we report for the first time the isolation of DNA aptamers directed
      against the whole tau protein, an important Alzheimer's disease (AD) biomarker.
      Non-SELEX approach based on the capillary electrophoresis partitioning technique
      was employed to isolate a high-affinity DNA sequence pool towards the target in
      only three rounds and one working day. High-throughput sequencing was next
      performed and the recognition ability of five selected aptamers was preliminary
      evaluated by surface plasmon resonance using the protein target immobilized on
      the chip. Finally, the analytical potential of the most affine aptamer was
      demonstrated through the design of a homogeneous-phase fluorescence anisotropy
      assay. This DNA aptamer was found to be able to recognize not only the whole tau
      441 but also the tau-381, tau-352, tau-383 isoforms. The sensing platform allowed
      the determination of these four targets with a detection limit of 28 nM, 3.2 nM,
      6.3 nM and 22 nM, respectively.

PMID- 30278901
TI  - SPE-LC-MS investigations for the isolation and fractionation of acidic oil
      degradation products.
AB  - In this study, we focus on isolation and fractionation strategies by solid phase
      extraction (SPE) for a broad range of environmentally related organic acids.
      These emerging potential contaminants are primary degradation products of spilled
      petrogenic compounds but little attention has been given to their environmental
      analysis and risk assessment. Three mixed-mode anion exchange sorbents possessing
      various backbone polarities were compared with respect to the extraction and
      fractionation efficiency. Quantitative analysis was obtained using an optimized
      and validated LC-MS method. We demonstrated the importance of reasonable ion
      source settings for highest sensitivity of individual carboxylic acids.
      Furthermore, fractionation of carboxylic acids into aliphatic and aromatic
      fractions by SPE was achieved by step-wise elution. Best performance regarding
      the isolation of low-concentration acids (sub MUg L-1 level) in complex samples
      was attributed to Strata XA and is caused by high secondary hydrophobic
      interactions in addition to the ionic interactions. Isolation and fractionation
      of acid spiked diesel-spilled harbor water (22 MUg L-1 spike level) revealed
      recoveries >80% for all tested carboxylic acids and low carry-overs of neutral
      petroleum compounds. We conclude that the isolation and fractionation of acidic
      degradation products by SPE is a powerful tool to investigate this new class of
      contaminants in relation to identification and ecological risk assessments.

PMID- 30278902
TI  - Ultra-performance supercritical fluid chromatography: A powerful tool for the
      enantioseparation of thermotropic fluorinated liquid crystals.
AB  - A fast and simple supercritical fluid chromatography method for the
      enantioseparation of twenty newly synthesized orthoconic antiferroelectric liquid
      crystals is reported for the first time. The effects of alkoxy spacer length and
      fluorine atom presence and position in the phenyl ring on chromatographic
      behavior were investigated. Baseline enantioseparation of all compounds was
      achieved using simple mobile phases consisting of carbon dioxide and alcohol as
      cosolvent on (3,5-dimethylphenylcarbamate) derivative of amylose as chiral
      stationary phase. The analysis times ranged from 2 to 4 and from 4 to 7 min for
      most samples when using methanol and propane-2-ol, respectively. The significant
      effect of cosolvent type on the enantioseparation of these compounds was assessed
      and partial complementarity of methanol and propane-2-ol was observed.

PMID- 30278903
TI  - Macro-mesoporous organosilica monoliths with bridged-ethylene and terminal-vinyl:
      High-density click functionalization for chromatographic separation.
AB  - A novel kind of macro-mesoporous organosilica monolith, with not only bridged
      ethylene groups incorporated into the skeleton but also terminal-vinyl groups
      protruded from the pore-wall, was prepared so that high-loaded double bonds were
      achieved. Via highly efficient "thiol-ene" click reaction of such high-loaded
      double bonds, the surface coverage of C18 groups on monolith could be 5.54 MUmol
      m-2, significantly larger than that of the reported separation materials,
      beneficial to improvement of separation resolution, especially for peptide
      separation. The separation performance was evaluated using alkylbenzenes and
      standard peptides. Furthermore, the tryptic digests of complex sample was
      successfully analyzed. Because of high separation resolution of our prepared
      hybrid monolith, the peak capacity for 6-h gradient was achieved as 482. Coupling
      to LTQ Orbitrap Velos Mass Spectrometry, 22523 tryptic peptides from 4423
      proteins were identified from the HeLa cells, more than that using the other long
      gradient separation by the same system reported, showing great promising of such
      monolith for large-scale in-depth proteomic analysis.

PMID- 30278904
TI  - Ultrasensitive and label-free electrochemical aptasensor of kanamycin coupling
      with hybridization chain reaction and strand-displacement amplification.
AB  - This work reports the proof-of-concept of an ultrasensitive label-free
      electrochemical aptasensor for Kanamycin (Kana) detection coupling strand
      displacement amplification (SDA) with hybridization chain reaction (HCR). In the
      presence of target Kana, the analyte triggers conformational change of hairpin
      HP1 (HP1) and two-staged SDA to produce short single-stranded DNA (S1) with the
      aid of KF polymerase and nicking endonuclease. Meanwhile, the as-produced S1
      hybridizes with the immobilized hairpin HP2 (HP2) on the electrode to open the
      hairpin, thereby resulting in the formation of DNA duplex. Thereafter, DNA duplex
      is selectively digested by Exo III accompanying S1 recycling. The residual single
      stranded probe (S2) on the electrode opens another two hairpins in sequence and
      propagates a chain reaction of hybridization events between two alternating
      hairpins (H1 and H2) to form a long nicked double-helix. Upon addition of redox
      active methylene blue (MB), numerous indicators are intercalated into the grooves
      of double-helix DNA polymers, each of which produces an electrochemical signal
      within the applied potentials. Under optimum conditions, the SDA/HCR-based
      electrochemical aptasensor exhibits a high sensitivity for detection of Kana down
      to 36 fM with a linear range from 0.05 to 200 pM. Additionally, the as-prepared
      aptasensor is successfully employed to determinate the Kana in animal derived
      food (milk). With the advantages of high sensitivity, label-free strategy and
      excellent selectivity, the developed aptasensor possesses great potential
      application value in food-safety analysis field.

PMID- 30278905
TI  - epsilon-MnO2-modified graphite electrode as a novel electrochemical sensor for
      the ultrasensitive detection of the newly FDA approved Hepatitis C antiviral drug
      ledipasvir.
AB  - A novel, simple and sensitive electrochemical method for the determination of
      ledipasvir (LED), the newly FDA approved Hepatitis C antiviral drug was developed
      and validated using epsilon-MnO2-modified graphite electrode. Two different MnO2
      polymorphs (gamma- and epsilon-MnO2 nanoparticles) were synthesized and
      characterized using X-ray powder diffraction (XRD), Fourier transform infrared
      (FTIR), energy dispersive X-ray (EDX) and thermogravimetric analysis (TGA).
      Surface area measurements show that epsilon-MnO2 NPs have large surface area of
      345 m2/g, which is extremely high if compared to that of gamma-MnO2 NPs (38
      m2/g). In addition, a comprehensive study of the difference in the
      electrochemical behavior of LED while using pencil graphite electrode (PGE)
      modified with either gamma- or epsilon-MnO2 NPs is carried out. It was found that
      surface area and percentage of surface hydroxyls of MnO2 NPs are the key factors
      governing the sensitivity of the fabricated electrode toward the oxidation of the
      positively charged LED. Scanning electron microscopy (SEM) was employed to
      investigate the morphological shape of MnO2 NPs and the surface of the bare and
      modified electrodes. Moreover, cyclic voltammetry and electrochemical impedance
      spectroscopy (EIS) were used for the surface analysis of the modified electrodes.
      Based on the obtained results, epsilon-MnO2/PGE was applied as a selective and
      sensitive electrode for determination of LED. Under the optimized experimental
      conditions, epsilon-MnO2/PGE provides a linear response over the concentration
      range of 0.025-3.60 MUmol L-1 LED with a low limit of detection, which was found
      to be 5.10 nmol L-1 (4.50 ng mL-1) for the 1st peak and 9.20 nmol L-1 (8.10 ng mL
      1) for the 2nd one. In addition, the oxidation behavior of LED is discussed with
      a full investigation of the oxidized product using FT-IR and LC/MS. The
      fabricated sensor exhibits a good precision, selectivity and stability and was
      applied successfully for the determination of LED in its tablets and real rat
      plasma samples with a good recovery using a simple extraction technique.

PMID- 30278906
TI  - Nitrogen doped chiral carbonaceous nanotube for ultrasensitive DNA direct
      electrochemistry, DNA hybridization and damage study.
AB  - In the interest of developing novel electrocatalyst for high performance DNA
      biosensing, with distinctive chiral double helix nanostructure, nitrogen doped
      chiral carbonaceous nanotube (Chiral-CNT) was employed for ultrasensitive label
      free DNA biosensing research. Chiral-CNT can quantitative detection of four DNA
      bases with high sensitivity and selectivity. Without any prehydrolysis and
      labeling process, direct electrochemistry of single-stranded DNA and double
      stranded DNA, qualitative and quantitative detection of DNA hybridization (low
      detection limit: 0.0268 g L-1) were realized. Moreover, sensitive detection of
      DNA damage induced by fenton reagent was also realized with low detection limit
      of 0.0350 mg mL-1 and high sensitivity of 7.42 MUA mg-1 mL. The high biosensing
      performance attributes to the unique chiral structure of Chiral-CNT, leads to
      efficient interreaction between Chiral-CNT and DNA molecule.

PMID- 30278907
TI  - Development of a cobalt(II) phthalocyanine- MWCNT modified carbon paste electrode
      for the detection of polyunsaturated fatty acids.
AB  - In this work the development of an electrochemical sensor for the determination
      of polyunsaturated fatty acids (PUFAs), in particular linoleic acid, in
      commercially available safflower oil as complex matrix is described. The sensor
      consists of a carbon paste electrode with cobalt(II) phthalocyanine, Co(II)Pc, as
      mediator and multiwalled carbon-nanotubes (MWCNT) as nanomaterial. As carrier
      medium a sodium borate buffer (0.1 M, pH 9) was used. PUFAs were detected at a
      working voltage of 0.35-0.45 V (vs. Ag/AgCl). The sensor development was carried
      out in a batch system with differential pulse voltammetry (DPV) and cyclic
      voltammetry (CV). Sensor specification was tested by using various fatty acids
      (stearic acid, oleic acid, linoleic acid, linolenic acid and arachidonic acid) as
      well as esterified fatty acids, resulting in a specific applicability towards
      PUFAs, especially linoleic acid (LAH). The optimized sensor was applied in a flow
      injection analysis system (FIA) for the analysis of PUFAs in complex matrix.
      Linoleic acid was used as standard substrate to determine the analytical
      parameters. The linearity ranges between 7.5 and 200 MUg mL-1 LAH, while the
      limit of detection was determined to be 2.5 MUg mL-1 and the limit of
      quantification is approximately 7.5 MUg mL-1 LAH. The LAH content was
      successfully detected in commercially available safflower oil via standard
      addition method and the results could be confirmed by a reference method. The
      PUFA content was calculated as LAH-equivalent.

PMID- 30278908
TI  - A novel gas sampling introduction interface for fast analysis of volatile organic
      compounds using radiofrequency pulsed glow discharge time of flight mass
      spectrometry.
AB  - An improved gas sample introduction interface is developed and characterized for
      gas chromatography coupling and for direct injection of volatile organic
      compounds (VOCs), in a pulsed glow discharge (pulsed-GD) ion source coupled to a
      time of flight mass spectrometer (TOFMS) that is typically used for direct solid
      analysis. The novel interface allows the introduction of the analytes in the
      flowing afterglow region of the GD (a few mm away from the negative glow region)
      to reduce plasma quenching effects. Analyte ion signals are acquired in the
      temporal afterglow region, where low fragmentation of the molecular species is
      produced, providing useful qualitative and quantitative molecular information
      (e.g. molecular ion). Analytical capabilities of the pulsed-GD ion source with
      the novel gas sampling interface provides improved performance compared to
      previous designs. In particular, limits of detection for the analysis of VOCs in
      air were below (better) that legally established limits according to Directive
      2008/50/EC of the European Parliament.

PMID- 30278909
TI  - New approach for e-cigarette aerosol collection by an original automatic aerosol
      generator utilizing melt-blown non-woven fabric.
AB  - Currently, there is lack of standardized conditions for the collection and
      analysis of e-cigarette (EC) aerosol. Considering the urgent need for the
      development of these guidelines, a procedure for EC aerosol analysis was
      developed. A novel automatic e-cigarette aerosol generator was designed. For the
      first time, melt-blown non-woven fabric was applied for the effective uptake of
      compounds released from vaporized e-liquid. The extraction procedure was
      optimized in terms of type of extraction solvent, amount of sorbent and solvent
      volume. For optimization, a model e-liquid containing flavour additives belonging
      to various chemicals group with various chemical properties was investigated. The
      aerosol trapping efficiency was satisfactory and was equal to 92 +/- 7%. Final
      determination was performed by GC-MS/MS. Quantitation was based on the mass
      change tracking approach (MCT), which assumes the monitoring of e-liquid mass
      changes before and after vaping. The combination of non-woven fabric and sampling
      approach (MCT) was proven to be effective in acquisition of reliable data. Thus,
      the concentrations in aerosol and emission factors were calculated for aerosols
      collected during the vaping of both model e-liquids and real samples. Validation
      was performed by evaluating key analytical parameters, such as linearity,
      accuracy, precision, limit of detection (LOD) and quantitation (LOQ). For all
      investigated compounds, recoveries from 70% to 118% together with precision and
      reproducibility below 12% were achieved. The applicability of the described
      approach was examined by analysing EC refill solutions commercially available on
      the Polish market.

PMID- 30278910
TI  - Design of an ultrasonic piezoelectric injection port for analysis of thermally
      unstable compounds using corona discharge ion mobility spectrometry.
AB  - This paper reports on a novel ultrasonic injection port designed and constructed
      to analyze thermally unstable chemical compounds using corona discharge ion
      mobility spectrometry (CD-IMS). In order to achieve the highest possible
      efficiency with the device, some parameters such as the solvent type, carrier gas
      flow rate and sample volume were exhaustively investigated. Through a comparative
      study conducted, it was revealed that unlike the thermal desorption system, the
      proposed ultrasonic injection port could easily be used for the analysis of some
      thermally unstable compounds such as carbaryl, propoxur and vitamin B1, by means
      of CD-IMS. To evaluate the potential of the device, carbaryl, extracted from
      different samples by dispersive liquid-liquid microextraction technique, was
      quantitatively analyzed. The CD-IMS-based results brought forth the detection
      limit of 0.03 mg L-1, and dynamic range of 0.1-10.0 mg L-1 with the determination
      coefficient of 0.9981. The relative standard deviations for one day and three
      consecutive days were 4 and 6%, respectively. Further, the spiked samples of
      agricultural wastewater, underground water, and tomato analyzed culminated in the
      recovery values of 83%, 98% and 82%, respectively. The satisfactory results
      proved an acceptable capability of the sample introduction system, to be
      conveniently used for routine analysis of thermally unstable compound, without
      any tedious derivatization.

PMID- 30278911
TI  - Hypersensitive quantification of global 5-hydroxymethylcytosine by chemoenzymatic
      tagging.
AB  - 5-hydroxymethylcytosine (5hmC) is an epigenetic DNA modification. Tissue-specific
      reduction in global 5hmC levels has been associated with various types of cancer.
      One of the challenges associated with detecting 5hmC levels is its extremely low
      content, especially in blood. The gold-standard for reliable global 5hmC
      quantitation is liquid chromatography-tandem mass spectroscopy (LC-MS/MS)
      operating in a multiple reaction monitoring (MRM) mode. Difficulties associated
      with 5hmC detection by LC-MS/MS include its low abundance, low ionization
      efficiency and possible ion suppression from co-eluted compounds. Hence,
      detecting 5hmC levels in blood samples for diagnosis of leukemia and other blood
      malignancies presents a unique challenge. To overcome these difficulties we
      introduce a simple chemoenzymatic method for specifically tagging 5hmC, resulting
      in an eight-fold increase in detection sensitivity. We demonstrate that we could
      quantitatively detect 5hmC levels in various human tissues, including blood
      samples from healthy individuals and leukemia patients, using the most basic
      quadrupole mass-analyzer instrument and only 200 ng of DNA. The limit of
      detection (LOD) of our technique is 0.001% 5hmC from 300 ng DNA, sufficient for
      future mass-spectroscopy based diagnostics of diseases associated with low 5hmC
      levels such as leukemia.

PMID- 30278912
TI  - Core-shell red silica nanoparticles based immunochromatographic assay for
      detection of Escherichia coli O157:H7.
AB  - In this paper, a new type immunochromatographic assay (ICA) based on core-shell
      red silica nanoparticles (core-shell red SiO2NPs) was proposed and used to detect
      Escherichia coli O157:H7 (E. coli O157:H7). This is the first report of
      qualitative ICA for detecting E. coli O157:H7 in phosphate buffer saline (PBS)
      and food sample using core-shell red SiO2NPs. Monodispersed red SiO2NPs were
      synthesized in the aqueous solution by modifying amino silane and C.I Reactive
      Red 136 on unmodified silica nanoparticles. The limit of detection (LOD) of this
      core-shell red SiO2NPs based ICA for E. coli O157:H7 was 4.5 * 105 CFU/mL in
      sterile PBS within 20 min. The LOD of this ICA strip for E. coli O157:H7 in milk
      and pork samples both were 4.5 * 106 CFU/mL. The core-shell red SiO2NPs based ICA
      for detection of E. coli O157:H7 has no cross activity with other bacteria. All
      these results show that this new kind of core-shell colored SiO2NPs is promising
      for the practical applications in ICA and other rapid detection fields.

PMID- 30278913
TI  - Rapid Access Cardiology (RAC) Services Within a Large Tertiary Referral Centre
      First Year in Review.
AB  - BACKGROUND: Rapid Access Cardiology (RAC) services are hospital co-located
      cardiologist-led outpatient clinics providing prompt assessment and management of
      chest pain. This service model is part of chest pain management in the United
      Kingdom. However, little data exists on RAC services in Australia. Our aim was to
      describe the introduction of RAC services to an Australian tertiary centre
      (utility, safety, and acceptability). METHODS: Referrals were accepted for low
      intermediate risk chest pain. Referrer and patient clinical data was collected
      prospectively in the first year of RAC - 4 February 2015 to 4 February 2016. Data
      was linked to hospital presentations/admissions to identify
      readmissions/mortality data. RESULTS: Among 520 patients (55.0% male, mean age
      55.2 years), 87.6% were referred from emergency and 68.4% assessed within 5 days.
      The final diagnosis was new coronary artery disease (CAD) in 7.9%, and 81.3% had 
      >=2 cardiovascular risk factors (diabetes, hyperlipidaemia, hypertension,
      overweight/obesity, smoker, pre-existing CAD, and chronic renal failure). On
      average, 0.8 cardiac tests were ordered per person. In total, 35 (6.7%) had
      invasive coronary angiograms, with 51.4% having obstructive CAD. Patients
      reported in surveys (82.8% response rate) that 93.0% "strongly agreed" RAC
      services were useful to the community. Referrers were also "very satisfied" with
      RAC (7/17) or "satisfied" (9/17). Furthermore, of 336 referrals, referrers
      reported without RAC they would admit the patient in 11.3% of cases. There were
      4.8% (25/520) unplanned cardiovascular readmissions and 0.6% (3/520) of these
      were for acute coronary syndromes and no deaths. CONCLUSIONS: Outpatient RAC
      services are an accepted, effective and safe pathway for management of low
      intermediate risk chest pain.

PMID- 30278914
TI  - Thrombogenic Porcelain Atrium.

PMID- 30278915
TI  - DEL1 protects against chondrocyte apoptosis through integrin binding.
AB  - BACKGROUND: Osteoarthritis (OA) is a debilitating disease process, affecting
      mobility and overall health of millions. Current treatment is for symptomatic
      relief and discovery of approaches to halt or reverse damage is imperative.
      Deletion of developmental endothelial locus-1 (Del1) has been shown to increase
      severity of OA in knockout mice. We examined the intracellular pathways involved
      in the ability of DEL1 to protect chondrocytes from apoptosis and anoikis and
      hypothesized that it functioned via integrin signaling. MATERIALS AND METHODS:
      Primary human chondrocytes were treated with various inducers of apoptosis,
      including anoikis, in the presence of added DEL1 or bovine serum albumin as
      control. Various inhibitors of integrin binding were examined for their effect on
      DEL1 activity. Downstream signaling pathway components were detected by
      immunoblotting. RESULTS: The addition of DEL1 protected chondrocytes from
      multiple inducers of apoptosis as measured by cell survival, terminal
      deoxynucleotidyl transferase dUTP nick end labeling and caspase 3/7 assays (P <
      0.05). The effect of DEL1 was blocked by RGD peptides and by antibodies directed
      to integrin alphaVbeta3, but not by controls or antibody to integrin alpha1 (P <
      0.05). Treatment with DEL1 promoted ERK and AKT activation when cells were
      attached, but only AKT activation under conditions of anoikis. CONCLUSIONS: DEL1
      protected chondrocytes from apoptosis in response to activators of either the
      intrinsic or extrinsic pathways, and to anoikis. This effect was mediated
      primarily through integrin alphaVbeta3. This represents a therapeutic target for
      therapies to prevent cartilage degeneration in OA.

PMID- 30278916
TI  - Lack of disparities in screening for associated anomalies in children with
      anorectal malformations.
AB  - INTRODUCTION: Patients with anorectal malformations (ARM) often have associated
      congenital anomalies and should undergo several screening exams in the first year
      of life. We hypothesized that racial and socioeconomic disparities exist in the
      screening processes for these patients. METHODS: After IRB approval, a
      retrospective review of patients with ARM born between 2005 and 2016 was
      performed at a quaternary care children's hospital. Demographics including
      gender, race, insurance, and zip code were collected. Zip code was used as a
      surrogate for median income. Chart review was performed to identify anomaly type
      and whether Vertebral defects, Anorectal malformations, Cardiac defects, Tracheo
      Esophageal fistula, Renal anomalies, and Limb abnormalities screening was
      performed within 1 y of age. Descriptive statistics and chi square analyses were
      performed. RESULTS: One hundred patients (59% male, 68% low malformation) were
      identified. African American and Caucasian subjects represented 41% and 40% of
      the population, respectively. Overall, 68 of 100 patients had at least one
      screening test for each of the Vertebral defects, Anorectal malformations,
      Cardiac defects, Tracheo-Esophageal fistula, Renal anomalies, and Limb
      abnormalities associations. Although some minor differences were noted (more
      African Americans received skeletal survey than Caucasians, 80.5% versus 60%, P =
      0.00335), no pattern of systematic bias in the receipt or timing of screening was
      evident based on race, insurance, or income. CONCLUSIONS: There do not appear to
      be racial or socioeconomic disparities in screening for associated anomalies in
      patients with ARM. However, overall gaps in screening still exist, and work must
      be carried out to appropriately screen all patients for associated anomalies.

PMID- 30278917
TI  - Isolated pancreatic tail remnants after transgastric necrosectomy can be
      observed.
AB  - BACKGROUND: Severe necrotizing pancreatitis may result in midbody necrosis and
      ductal disruption leaving an isolated pancreatic tail. The purpose of this study
      was to characterize outcomes among patients with an isolated tail remnant who
      underwent transgastric drainage or necrosectomy (endoscopic or surgical) and
      determine the need for subsequent operative management. MATERIALS AND METHODS:
      Patients with necrotizing pancreatitis and retrogastric walled-off collections
      treated by surgical transgastric necrosectomy or endoscopic cystgastrostomy +/-
      necrosectomy between 2009 and 2017 were identified by a retrospective chart
      review. All available preprocedure and postprocedure imaging was reviewed for
      evidence of isolated distal pancreatic tail remnants. RESULTS: Seventy-four
      patients were included (40 surgical and 34 endoscopic). All the patients in the
      surgical group underwent laparoscopic transgastric necrosectomy; the endoscopic
      group consisted of 26 patients for pseudocyst drainage and eight patients for
      necrosectomy. A disconnected pancreatic tail was identified in 22 (29%) patients
      (13 laparoscopic and nine endoscopic). After the creation of the
      "cystgastrostomy," there were no external fistulas despite the viable tail. Of
      the 22 patients, four patients developed symptoms at a median of 23 months (two,
      recurrent episodic pancreatitis; two, intractable pain). Two patients (both
      initially in endoscopic group) ultimately required distal pancreatectomy and
      splenectomy at 24 and 6 months after index procedure. CONCLUSIONS: Patients with
      a walled-off retrogastric collection and an isolated viable tail are effectively
      managed by a transgastric approach. Despite this seemingly "unstable anatomy,"
      the creation of an internal fistula via surgical or endoscopic "cystgastrostomy"
      avoids external fistulas/drains and the short-term necessity of surgical distal
      pancreatectomy. A very small subset requires intervention for late symptoms.

PMID- 30278918
TI  - IDH1 mutation correlates with a beneficial prognosis and suppresses tumor growth
      in IHCC.
AB  - BACKGROUND: Isocitrate dehydrogenase 1/2 (IDH1/2) mutations have been reported in
      intrahepatic cholangiocarcinoma (IHCC). However, the prognosis of a single IDH1
      mutation and impact of mutant IDH1 on IHCC tumor growth remain unclear. METHODS:
      A total of 85 IHCC tumor samples were sequenced. Prognosis and
      clinicopathological correlation were analyzed. The role of mutant IDH1 in IHCC
      tumor growth was measured by cell proliferation assay, colony formation assay in
      soft agar, and xenograft tumor models. Akt, ERK, p38 MAPK, and JNK signaling,
      which commonly affect tumor growth, were examined by Western blotting to explore
      the potential mechanism. RESULTS: IDH1 mutations correlated with a beneficial
      prognosis and smaller tumor size. Mutant IDH1 exhibited a growth-inhibitory
      effect on IHCC cell lines in vitro and in vivo. Akt signaling was suppressed in
      IHCC cell lines expressing a mutant IDH1. The reactivation of Akt signaling by
      SC79 restored the inhibited growth of cell lines expressing a mutant IDH1 in
      IHCC. CONCLUSIONS: Collectively, we demonstrated that mutant IDH1 correlates with
      a beneficial prognosis and inhibits tumor growth by suppressing Akt signaling in
      IHCC. We suggest that patients with IDH1 mutations could be considered for both
      less-aggressive therapy and therapy tailored to the presence of their mutant
      enzyme in the future.

PMID- 30278919
TI  - Insurance status and pediatric mortality in nonaccidental trauma.
AB  - BACKGROUND: Nonaccidental trauma (NAT) is a leading cause of injury and death in
      early childhood. We sought to understand the association between insurance status
      and mortality in a national sample of pediatric NAT patients. MATERIALS AND
      METHODS: We performed a retrospective cohort study using the 2012-2014 National
      Trauma Databank. We included children <=18 y hospitalized with NAT (The
      International Classification of Diseases, Ninth Revision codes: E967-968). The
      primary exposure was insurance status (categorized as public, private, and
      uninsured). The primary outcome was emergency department or inpatient mortality
      from NAT. RESULTS: We identified 6389 children with NAT. Mean age was 1.6 y
      (standard deviation 3.7), with 41% female and 42% of an ethnic or racial
      minority. Most were publicly insured (77%), with 17% privately insured and 6%
      uninsured. Mean injury severity score (ISS) was 13.9 (standard deviation 10.3).
      Overall, 516 (8%) patients died following NAT. Compared to patients who survived,
      those who died were more likely to be younger (mean age 1.0 y versus 1.6 y; P <
      0.001), uninsured (13% versus 6%; P < 0.001), transferred to a higher-care
      facility (57% versus 49%; P < 0.001), and more severely injured (mean ISS 25.9
      versus 12.8; P < 0.001). After adjusting for age, race, transfer status, and ISS,
      uninsured patients had 3.3-fold (95% CI = 2.4-4.6) greater odds of death compared
      to those with public insurance. For every 1 point increase in ISS, children had
      12% (95% CI = 11%-13%) increased adjusted odds of death. CONCLUSIONS: Pediatric
      patients without insurance had significantly greater odds of death following NAT,
      compared to children with public insurance. Knowledge that uninsured children
      comprise an especially vulnerable population is important for targeting potential
      interventions.

PMID- 30278920
TI  - Pregnancy after a melanoma diagnosis in women in the United States.
AB  - BACKGROUND: Melanoma is the third most common cancer in women aged 18-39 years.
      Medical literature recommends that women wait for at least 2 years before
      becoming pregnant, yet few studies have examined pregnancy after melanoma. Our
      aims were to investigate the pregnancy rate after a melanoma diagnosis and the
      relationship between melanoma treatment and subsequent pregnancy. METHODS: We
      studied women with a melanoma diagnosis in the Truven Health MarketScan database.
      Women with a melanoma diagnosis were matched 1:1 to women with no melanoma
      diagnosis to compare pregnancy rates between groups. For women with melanoma, Cox
      models were fitted for rates of pregnancy overall, pregnancy if postsurgical
      treatment was received, and for treatment after pregnancy. RESULTS: The sample
      included 11,801 women aged 18-40 years with melanoma, who were not pregnant on
      the index date. These women had a higher rate of pregnancy within 2 years
      compared to matched controls (15.8% versus 13.6%, P < 0.001). For 0-9 months
      after diagnosis, women who received postsurgical treatment had a 74% lower
      probability of becoming pregnant (hazard ratio = 0.26, P = 0.003). Rates of
      treatment received after pregnancy were not significantly different (hazard ratio
      = 0.68, P = 0.23). CONCLUSIONS: Our study is the largest review of postmelanoma
      pregnancy in the United States. After a melanoma diagnosis, women had a slightly
      higher rate of pregnancy than matched controls, indicating that women are not
      delaying pregnancy. However, women who received advanced treatment for melanoma
      had a lower rate of pregnancy than untreated women. Women who became pregnant
      after a melanoma diagnosis did not have an increased risk of requiring subsequent
      treatment for melanoma.

PMID- 30278921
TI  - Large animal models for long-segment tracheal reconstruction: a systematic
      review.
AB  - BACKGROUND: The reconstruction of extensive tracheal defects is an unresolved
      problem. Despite decades of research, a reliable and practical substitute remains
      to be found. While there have been clinical reports of successful long-segment
      tracheal reconstruction, reproducibility and widespread applicability of these
      techniques have yet to be achieved. Large animals such as the dog, pig, sheep,
      and goat have comparable tracheal morphology and physiology to humans making them
      useful preclinical models to screen potential therapeutic strategies. MATERIALS
      AND METHODS: The literature was reviewed to identify large animal models commonly
      used for tracheal reconstruction. A systematic search of PubMed and EMBASE was
      performed for large animal studies reporting on the reconstruction of long
      segment tracheal and carinal defects. Fifty-seven studies were identified for
      analysis. RESULTS: There is no standard large animal model available for tracheal
      research. In recent years, livestock species have gained favor over dogs as
      animal models in this field. The minimum requirements for successful tracheal
      replacement are rigidity, vascularity, and epithelial lining. Early attempts with
      synthetic prostheses were met with disappointing results. An autologous tracheal
      substitute is ideal but hindered by limited donor site availability and the lack
      of a dominant vascular pedicle for microsurgical reconstruction. Although
      tracheal allotransplantation enables like-for-like replacement, there are
      unresolved issues relating to graft vascularity, immunosuppression, and graft
      preservation. Tissue engineering holds great promise; however, the optimal
      combination of scaffold, cells, and culture conditions is still indeterminate.
      CONCLUSIONS: Despite impressive advances in tracheal reconstruction, a durable
      substitute for extended tracheal defects continues to be elusive.

PMID- 30278922
TI  - Pleural electrical impedance is a sensitive, real-time indicator of pneumothorax.
AB  - BACKGROUND: Chest tube management protocols, particularly in patients with
      alveolar-pleural air leak due to recent surgery or trauma, are limited by
      concerns over safety, especially concerns about rapid and occult development of
      pneumothorax. A continuous, real-time monitor of pneumothorax could improve the
      quality and safety of chest tube management. We developed a rat model of
      pneumothorax to test a novel approach of measuring electrical impedance within
      the pleural space as a monitor of lung expansion. MATERIALS AND METHODS:
      Anesthetized Sprague-Dawley rats underwent right thoracotomy. A novel impedance
      sensor and a thoracostomy tube were introduced into the right pleural space.
      Pneumothorax of varying volumes ranging from 0.2 to 20 mL was created by syringe
      injection of air via the thoracostomy tube. Electrical resistance measurements
      from the pleural sensor and fluoroscopic images were obtained at baseline and
      after the creation of pneumothorax and results compared. RESULTS: A statistically
      significant, dose-dependent increase in electrical resistance was observed with
      increasing volume of pneumothorax. Resistance measurement allowed for continuous,
      real-time monitoring of pneumothorax development and the ability to track
      pneumothorax resolution by aspiration of air via the thoracostomy tube. Pleural
      resistance measurement demonstrated 100% sensitivity and specificity for all
      volumes of pneumothorax tested and was significantly more sensitive for
      pneumothorax detection than fluoroscopy. CONCLUSIONS: The electrical impedance
      based pleural space sensor described in this study provided sensitive and
      specific pneumothorax detection, which was superior to radiographic analysis.
      Real-time, continuous monitoring for pneumothorax has the potential to improve
      the safety, quality, and efficiency of postoperative chest tube management.

PMID- 30278923
TI  - Electromagnetic navigational bronchoscopic airway recanalization in patients with
      vanishing bronchus.
AB  - BACKGROUND: Stenosis is the most frequent airway complication after lung
      transplantation. When complete obstruction is diagnosed without possibility of
      recanalization, options are generally limited to either resection or
      retransplantation, both associated with increased morbidity and mortality. We
      describe our experience with a novel technique using electromagnetic navigational
      bronchoscopy (ENB) to recanalize the occluded airway after lung transplantation.
      METHODS: Patients who underwent lung transplantation between 2010 and 2016 with
      subsequent development of complete airway obstruction and failed conventional
      recanalization attempts were included in this study. All patients underwent
      attempted recanalization using ENB. Primary outcomes included success of the
      technique and long-term patency. Secondary outcomes included procedure-related
      complications. RESULTS: Four patients met inclusion criteria and underwent
      attempted recanalization using the ENB platform. Location of the obstruction was
      the bronchus intermedius in two patients, the lingular bronchus in one patient,
      and the left basilar bronchus in one patient. Mean length of stenosis was 8.8 mm.
      Three patients (75%) were successfully recanalized and all airways remain patent
      at 1, 48, and 66 mo. There were no procedure-related complications. The one
      patient who was unable to be recanalized successfully underwent bilobectomy and
      died 7 mo later. CONCLUSIONS: ENB is a feasible method of airway recanalization
      in select patients with bronchial occlusion after lung transplantation. ENB
      recanalization spares lung parenchyma and avoids risks associated with surgical
      resection and retransplantation. This novel technique can be added to the
      armamentarium for thoracic surgeons who diagnose and treat this complicated
      problem.

PMID- 30278924
TI  - Outcomes in video-assisted thoracoscopic surgery lobectomies: challenging
      preconceived notions.
AB  - BACKGROUND: Most thoracic surgical procedures in the United States are being
      performed by general surgeons (GSs) without any advanced training. With the
      recent approval of computed tomography screening for lung malignancy in high-risk
      populations, the number of thoracic oncologic resections is expected to rise.
      Previous literature has demonstrated consistently worsened outcomes for patients
      undergoing thoracic surgical procedure when done by nonthoracic fellowship
      trained surgeons. Using the American College of Surgeons National Surgical
      Quality Improvement Project database, we examined short-term outcomes in patients
      undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for malignancy.
      MATERIALS AND METHODS: Data were obtained from the American College of Surgeons
      National Surgical Quality Improvement Project from 2010-2015. We identified
      patients who had an International Classification of Disease 9 diagnosis of lung
      cancer (162) who underwent VATS lobectomy (current procedural terminology 32663).
      We included only adults (>=18y) and elective cases. We excluded patients who had
      preoperative diagnosis of sepsis, contaminated wound class, or those patients
      with missing American Society of Anesthesiologists classification, morbid
      obesity, functional status, length of stay (LOS), or sex, and race information.
      We identified two groups by specialty: GS versus cardiothoracic (CT) surgeon. We
      then performed univariate analysis. We then performed propensity score analysis
      using a 1:3 ratio of general surgery patients to CT patients. Outcomes of
      interest included 30-d postoperative mortality, 30-d postoperative morbidity, and
      LOS. RESULTS: A total of 4105 patients were identified, 607 performed by GSs,
      3508 performed by CT surgeons. The mean age for patients who underwent
      lobectomies by GSs was 68.6 versus 67.8 in the CT surgeon group (P < 0.05). The
      majority were female (58.09% GS versus 57.74% CT surgeon). There was a
      statistically significant difference in race between groups; patients were more
      likely to be African American in the CT surgeon group. Operative time was lower
      in the GS group as opposed to the CT surgeon group 179 min versus 196 (P < 0.01).
      Univariate analysis (mortality <0.1 CT surgeon and GS) and 1:3 propensity score
      matched analysis (0.08 GS% versus 0.08% CT surgeon) failed to demonstrate a
      significant difference in mortality. There was a statistically significant
      difference in median LOS between groups (6.2 GS versus 5.1 CT surgeon).
      Univariate and propensity matched analyses of pneumonia, sepsis, wound infection,
      deep vein thrombosis, transfusion requirement, myocardial infarction stroke,
      postoperative renal insufficiency, failure to wean, pulmonary embolism,
      reintubation, and deep organ space infection all failed to demonstrate a
      statistically significant difference between our groups of interest. Urinary
      tract infection was noted to be higher in the GS group operating room 2.29 as
      compared to the CT surgeon group (P value 0.02). CONCLUSIONS: In this large
      observational study, we found that VATS lobectomies performed by GS compared to
      the matched CT surgeon cohort had shorter operative time, and there was no
      difference in major postoperative morbidity or mortality. However, LOS was higher
      and there was increased risk of urinary tract infection in the GS compared to
      matched CT surgeon cohort.

PMID- 30278925
TI  - Free vascularized fascia flap combined with skin grafting for deep toe ulcer in
      diabetic patients.
AB  - BACKGROUND: This study introduces a technique for the reconstruction of deep toe
      defects in diabetic patients using a method that combines free vascularized
      fascia flap with skin grafting. METHODS: In this retrospective study, conducted
      between March 2010 and February 2016, 15 diabetic patients with deep toe ulcer
      received surgeries that combined free vascularized fascia flap with skin
      grafting, including nine anterolateral thigh fascia lata flaps and six
      superficial temporal fascia flaps. Their medical records were systematically
      reviewed from electronic databases. The donor artery was anastomosed to the
      dorsalis pedis artery in an end-to-side manner, and the vein was anastomosed to
      the accompanying vein in an end-to-end manner. RESULTS: Thirteen fascia flaps
      completely survived without any rejection. Partially necrosed grafted skins,
      which were found in two cases, were healed after routine dressing changes.
      Patients achieved an esthetic outcome and acceptable functions without further
      revisions. Two patients suffered from ischemic necrosis of the fascia flap and
      eventually underwent amputation. CONCLUSIONS: The present study demonstrated that
      vascularized fascia flap combined with skin grafting has great advantages for
      correcting deep toe ulcer in diabetic patients characterized by the esthetic
      outcome, abundant vascularity, surgical simplicity, and good deformability.

PMID- 30278926
TI  - The impact of location on the prognosis of squamous cell carcinomas of the
      anorectal region.
AB  - BACKGROUND: Because anal and rectal squamous cell carcinomas (R-SCCs and A-SCCs)
      share a common histology and an excellent response to chemoradiation, we
      hypothesized that R-SCC and A-SCC may represent a similar biological entity, and
      location would not affect clinical presentation and prognosis. METHODS: Patients
      diagnosed with R-SCC (n = 2881) and A-SCC (n = 21,854) were identified in the
      Surveillance, Epidemiology, and End Results database (1998-2013). R-SCCs were
      staged based on American Joint Committee on Cancer classification for A-SCC, and
      impact of location was analyzed accordingly. RESULTS: Compared to A-SCC, R-SCCs
      were more common in females (65% versus 48%, P < 0.001) and older patients (62
      versus 56 yrs, P < 0.001). R-SCC presented with more advanced disease than A-SCC:
      mean size 4.2 versus 3.6 cm; T4 14% versus 5%; nodal involvement 20% versus 15%;
      and metastases 13% versus 6% (all P < 0.001). In multivariable analysis, R-SCCs
      and A-SCCs had similar disease-specific survival (DSS) for stages 0, I, and III;
      however, stage II R-SCC had significantly worse DSS than A-SCCs (P = 0.002). This
      was due to a greater proportion of T3 (>5 cm) R-SCC tumors (36% versus 27%, P <
      0.001), which had a lower DSS than T2 (2-5 cm) tumors. Within T3 and T4 tumors, R
      SCCs had lower DSS than A-SCCs. CONCLUSIONS: R-SCC presented with higher stages
      than A-SCC, suggesting a delayed diagnosis. Larger R-SCC (T3-T4) had worse
      survival compared to T3-4 A-SCC, which may be due to a combination of more
      advanced disease within-stage as well as the use of less efficacious therapeutic
      regimens. Therefore, location may represent a significant prognostic factor for
      SCC of the anorectal region.

PMID- 30278927
TI  - Minimally invasive surgical exposure among US and Canadian pediatric surgery
      trainees, 2004-2016.
AB  - BACKGROUND: Minimally invasive pediatric surgery has increased in breadth and
      complexity over the past several decades, with little data on minimally invasive
      surgery (MIS) training in US and Canadian pediatric surgery fellowship programs.
      METHODS: We performed a time series analysis of Accreditation Council for
      Graduate Medical Education pediatric surgery fellow case logs from 2003 to 2016.
      Proportions of cases performed in an MIS fashion as well as per-fellow MIS case
      averages were recorded over time. RESULTS: There was a 30.9% increase in average
      number of MIS cases per fellow over the study time period. Twenty-three recorded
      procedures included MIS and open options (17 abdominal, three thoracic, and three
      genitourinary). The proportion of cases performed using a minimally invasive
      approach increased by an average of 29.0%, 14.6%, and 47.0% for each of these
      categories, respectively. Significant variability was observed in specific cases
      such as laparoscopic and open inguinal hernias, ranging from 0 to 85 and nine to
      152 per trainee, respectively, in the final year of data collection. When
      examining pyloromyotomy, a high-volume procedure with a known increase in the MIS
      approach, the proportion of cases performed MIS increased by 83.3%. The minimum
      and maximum number of cases per fellow recorded ranged from 0 to 114 during the
      eight years in which MIS pyloromyotomy was recorded. CONCLUSIONS: MIS case
      exposure among graduating US and Canadian pediatric survey fellows increased
      substantially during the study period. More granular data, however, are needed to
      better define the current operative experience and criteria for determination of
      competency in advanced MIS.

PMID- 30278928
TI  - Examining length of stay after commonly performed surgical procedures in ACS
      NSQIP pediatric.
AB  - BACKGROUND: The objective of this study was to identify ranges of postoperative
      length of stay (LOS) for common pediatric procedures using a large multi
      institutional database. MATERIALS AND METHODS: A retrospective analysis of the
      most frequently performed general surgical procedures in the ACS-NSQIP Pediatric
      (2013-2015) was performed. These included laparoscopic appendectomy (LA),
      laparoscopic cholecystectomy, laparoscopic gastrostomy, laparoscopic
      esophagogastric fundoplication (LF), thoracoscopic repair of pectus excavatum
      (TPE), open appendectomy (OA), enterostomy closure (OEC), gastrostomy closure
      (OGC), and bowel resection (OBR). Patients aged <6 mo or >18 y, operations with
      major concurrent procedures, same-day discharges, operations performed >2 d after
      admission, and inpatient deaths were excluded. Postoperative LOS was examined for
      each procedure, including multivariable analysis of risk factors for
      postoperative LOS > 75th percentile. RESULTS: A total of 29,557 cases were
      identified and included procedure subgroups ranging from 505 (OBR) to 19,260 (LA)
      cases. Procedure-specific median postoperative LOS (75th percentile; 90th
      percentile) were LA 1 d (2 d; 5 d); laparoscopic cholecystectomy 1 d (1 d; 2 d);
      laparoscopic gastrostomy 2 d (2 d, 4 d); laparoscopic fundoplication 3 d (4 d, 6
      d); thoracoscopic repair of pectus excavatum 4 d (5 d, 6 d); OA 3 d (6 d, 9 d);
      OEC 4 d (6 d, 10 d); OGC 1 d (1 d, 2 d); and OBR 6 d (10 d, 20 d). Preoperative
      risk factors for high postoperative LOS varied by procedure and included patient
      demographics, admission factors, case characteristics, and comorbidities.
      CONCLUSIONS: The range of postoperative LOS and risk factors for high
      postoperative LOS for commonly performed procedures varied considerably. These
      results may be a useful reference for benchmarking and resource utilization
      analyses at the institutional and health systems levels.

PMID- 30278929
TI  - Rapid growth speed of cysts can predict malignant intraductal mucinous papillary
      neoplasms.
AB  - BACKGROUND: Branch duct intraductal papillary mucinous neoplasm (BD-IPMN) has the
      potential for malignant transformation. Current risk factors used to predict
      malignant transformation, such as mural nodules and cyst size > 30 mm, are
      insufficient. Therefore, we aimed to investigate the predictive significance of
      cyst growth speed. MATERIALS AND METHODS: Between 2006 and 2017, 102 patients
      underwent pancreatectomy for IPMN. Of these, 50 patients with pathologically
      diagnosed BD-IPMN were selected for cyst growth analysis. Cyst growth speed,
      total cyst growth, and cyst growth rate were calculated retrospectively using the
      maximum diameter of the cyst at the first diagnosis and images taken
      preoperatively. RESULTS: Of the 50 BD-IPMN cases, 33 were diagnosed as benign
      (low to intermediate dysplasia) and 17 were malignant (10 high-grade dysplasias
      and seven invasive carcinomas). While no significant differences were observed in
      the presence of enhancing mural nodules or cyst size, malignant IPMN grew at a
      significantly faster speed (5.7 versus 1.6 mm/y; P < 0.001), greater amount of
      cyst diameter (10.1 versus 3.1 mm; P = 0.015), and greater percentage of cyst
      diameter (28.5% versus 9.5%; P = 0.006) than those of benign IPMN. Receiver
      operator characteristic curve analysis indicated that cyst growth speed had the
      greatest predictive performance among these three factors. Cyst growth speed >
      3.5 mm/y was demonstrated to predict malignant IPMN with a sensitivity of 88% and
      specificity of 91%. CONCLUSIONS: Cyst growth speed > 3.5 mm/y may be a good
      predictor for malignant IPMN. It can improve the diagnostic accuracy and optimize
      surgery for BD-IPMN.

PMID- 30278930
TI  - Functional inclusivity of trauma networks: a pilot study of the North West London
      Trauma Network.
AB  - BACKGROUND: Metrics exist to assess and validate trauma system outcomes; however,
      these are clinically focused and do not evaluate the appropriateness of admission
      patterns, relative to geography and triage category. We propose the term
      "functional inclusivity", defined as the number and proportion of triage
      negative, and/or nonseverely injured patients, who were injured in proximity to a
      level II/III trauma center but admitted to a level I facility. The aim of this
      study was to evaluate this metric in the North West London Trauma Network.
      METHODS: Retrospective, geospatial, observational analysis of registry data from
      the North West London Trauma Network. We included all adult (>=16 years) patients
      transported to the level I trauma center at St. Mary's Hospital between 1/1/13
      31/12/16. Incident location data were geocoded into longitude/latitude, and drive
      times were calculated from incident location to each hospital in London's Trauma
      System, using Google Maps. RESULTS: Of 2051 patients, 907 (44%) were severely
      injured (injury severity score [ISS] >=15), and 1144 (56%) were nonseverely
      injured (ISS 1-15). Seven hundred ninety five of the 1144 nonseverely injured
      patients (69%) were injured in proximity to a level II/III but taken to the level
      I facility. A total of 488 (24%) patients were triage-negative, and 229 (47%) of
      these were injured in proximity to a level II/III, but taken to the level I
      trauma center. CONCLUSIONS: This study has demonstrated the concept of functional
      inclusivity in characterizing trauma system performance. Further work is required
      to establish what constitutes an acceptable level of functional inclusivity and
      what the denominator should be, as well as validating and further evaluating the
      concept of functional inclusivity.

PMID- 30278931
TI  - Protective effects of thymoquinone on the healing process of experimental left
      colonic anastomosis.
AB  - PURPOSE: Colorectal cancer is globally the third most common cancer. Anastomotic
      complications remain to be an important issue for colorectal surgery. The aim of
      this study was to investigate the protective effects of thymoquinone (TQ) on the
      healing process of left colonic anastomosis in an experimental model. METHODS:
      Thirty-two male rats were divided into two groups, as the TQ group and the
      control group. TQ was administered to the TQ group, whereas the control group was
      given a standard feed and water for 2 wk. Following the creation of a left
      colonic anastomosis, subjects in both groups were sacrificed on the postoperative
      (PO) third and seventh days. Anastomotic burst pressures were measured
      mechanically. Immunohistochemical stainings for proliferating cell nuclear
      antigen, cluster of differentiation (CD) 31, CD45 were performed, and the matrix
      metalloproteinase-2 levels were measured. Histologic total scores were calculated
      according to Ehrlich-Hunt model. A value of P < 0.05 was considered as
      statistically significant. RESULTS: One rat in the control group that died on the
      PO fourth day was excluded. Anastomotic burst pressures on the PO seventh day
      were higher in the TQ group than the control group (P < 0.01). Histopathological
      total scores on the PO third and seventh days were higher in the TQ group (P <
      0.01). In addition, the TQ group revealed lower matrix metalloproteinase-2 scores
      on the PO third day and higher hydroxyproline levels on the PO seventh day (P <
      0.05 and P < 0.01, respectively). CONCLUSIONS: The use of TQ in colorectal
      surgery cases with left-sided colonic anastomosis resulted with increased
      anastomotic burst pressures and increased tissue hydroxyproline levels.

PMID- 30278933
TI  - Hepatorenal protection during renal ischemia by quercetin and remote ischemic
      perconditioning.
AB  - BACKGROUND: Pathogenesis of renal ischemia/reperfusion injury (IRI) involves
      oxidative stress response in the kidney and remote organs. Both quercetin and
      remote ischemic perconditioning (RIPerC) can protect partially against IRI. This
      study determined whether combined quercetin and RIPerC could provide an augmented
      hepatorenal protection against renal IRI. MATERIALS AND METHODS: I/R was induced
      by clamping renal arteries for 45 min followed by 24-h reperfusion. RIPerC
      consisted of four cycles of 2 min of left femoral artery ischemia followed by 3
      min of reperfusion administered at the beginning of renal ischemia. Rats were
      divided into five groups: sham, I/R, RIPerC, quercetin (Q + I/R), and combined
      quercetin and RIPerC (Q + RIPerC). At the end of reperfusion period, blood,
      urine, and tissue samples were collected. RESULTS: I/R caused kidney dysfunction,
      as proved by significant decrease in creatinine clearance, and a significant
      increase in liver functional indicators as evidenced by increased plasma alanine
      aminotransferase and aspartate aminotransferase activity. This was accompanied by
      a decrease of glutathione peroxidase and catalase activities with an increase of
      malondialdehyde levels and histological damages in renal and hepatic tissues.
      Treatment with RIPerC and quercetin reduced all these changes. However, the
      measure of improvements was enhanced by combined quercetin and RIPerC treatment.
      CONCLUSIONS: This study demonstrated protective effects of quercetin and RIPerC
      strategy on the both kidney and liver after renal I/R. The results suggest that
      combined quercetin and RIPerC provides an enhanced protection against renal IRI
      by reduction of lipid peroxidation and augmentation of antioxidant systems.

PMID- 30278932
TI  - Comparing outcomes with thoracic epidural and intercostal nerve cryoablation
      after Nuss procedure.
AB  - BACKGROUND: This study aimed to evaluate postoperative outcomes after minimally
      invasive repair of pectus excavatum (Nuss procedure) using video-assisted
      intercostal nerve cryoablation (INC) compared to thoracic epidural (TE).
      MATERIALS AND METHODS: We performed a single center retrospective review of
      pediatric patients who underwent Nuss procedure with INC (n = 19) or TE (n = 13)
      from April 2015 to August 2017. Preoperative, intraoperative, and postoperative
      characteristics were collected. The primary outcome was length of stay (LOS) and
      secondary outcomes were intravenous and oral opioid use, pain scores, and
      complications. Opioids were converted to oral morphine milligram equivalents per
      kilogram (oral morphine equivalent [OME]/kg). Mann-Whitney U test was used for
      continuous and chi-squared analysis for categorical variables. RESULTS: There
      were no significant differences in patient characteristics, except Haller Index
      (INC: median [interquartile range] 4.3 [3.6-4.9]; TE: 3.2 [2.8-4.0]; P = 0.03).
      LOS was shorter with INC (INC: 3 [3-4] days; TE: 6 [5-7] days; P < 0.001). Opioid
      use was higher intraoperatively (INC: 1.08 [0.87-1.37] OME/kg; TE: 0.46 [0.37
      0.67] OME/kg; P = 0.002) and unchanged postoperatively (INC: 1.78 [1.26-3.77]
      OME/kg; TE: 1.82 [1.05-3.37] OME/kg; P = 0.80), and prescription doses were lower
      at discharge in INC (INC: 30 [30-40] doses; TE: 42 [40-60] doses; P = 0.005).
      There was no significant difference in postoperative complications (INC: 42.1%;
      TE: 53.9%; P = 0.51). CONCLUSIONS: INC during Nuss procedure reduced LOS,
      shifting postoperative opioid use earlier during admission. This may reflect the
      need for improved early pain control until INC takes effect. Prospective
      evaluation after INC is needed to characterize long-term pain medication
      requirements.

PMID- 30278934
TI  - Risk factors for 30-day readmission after colorectal surgery: does transfer
      status matter?
AB  - BACKGROUND: Rates of readmission after colorectal surgery (CRS) range from 9% to
      25% and cost the US $300 million annually. The aim of this study was to identify
      risk factors for 30-d readmission after CRS. Our hypothesis was that transfer
      from an outside hospital before CRS increases incidence of 30-d readmission.
      METHODS: Using the Healthcare Cost and Utilization Project Nationwide
      Readmissions Database, a retrospective analysis of surviving adult patients who
      underwent inpatient colon and/or rectal resection from 2010 to 2014 was
      performed. Using multivariable logistic regression, we assessed the direct effect
      of potential risk factors for readmission, including demographics, hospital
      characteristics, comorbidities, indication for CRS, and transfer status to the
      index hospital where the CRS was performed. RESULTS: A total of 336,792 patients
      were included, and 13% (n = 43,546) were readmitted within 30 d. Overall, 1% of
      patients (n = 3652) were transferred from another hospital for surgery, and these
      patients were more likely to be older, have comorbidities, have public insurance,
      and have low income. After adjustment, age, insurance type, household income,
      comorbidities, and primary indication for CRS were all significant predictors of
      readmission. Transfer status did not meaningfully impact the incidence of
      readmission after accounting for patient and hospital characteristics (aOR 1.08,
      95% CI 1.00, 1.18). Patients with primary indications of trauma (aOR 1.88, 95% CI
      1.48, 2.38), inflammatory bowel disease (aOR 1.64, 95% CI 1.1.56, 1.71), and
      ischemia (aOR 1.77, 95% CI 1.1.59, 1.97) were most likely to be readmitted.
      Patients treated at a rural nonteaching hospital, compared with those at a urban
      teaching hospital, were significantly less likely to be readmitted (aOR 0.80, 95%
      CI 0.76, 0.83). CONCLUSIONS: Preoperative factors, such as patient comorbidities
      and primary indications for CRS, are important risk factors for postoperative
      readmission. Although transfer status does not independently predict readmission,
      it serves as a proxy for a high-risk group of patients that could be targeted for
      future interventions.

PMID- 30278935
TI  - Magnetic compression technique for colonic anastomosis in rats.
AB  - BACKGROUND: Magnetic compression technique (MCT) is useful for construction of
      digestive tract anastomoses in pigs and dogs. This study determined the efficacy
      of MCT for performing colonic anastomosis in rats. METHODS: Twenty male Sprague
      Dawley rats (230-280 g) were randomly apportioned to a study group that underwent
      colonic anastomosis with MCT or a control group subjected to hand-sewn colonic
      anastomosis. The groups were compared for time to construct the anastomosis,
      survival rate, and postoperative complications. Animals were euthanized at 1 mo
      postsurgery to study the burst pressure and histology of the anastomoses.
      RESULTS: The study group required significantly less time to construct the
      anastomosis (6.50 +/- 1.58 min) than did the control (15.6 +/- 2.22 min). The
      survival rate of the study group (100%) was significantly higher than that of the
      control group (60%). In the control group, three rats developed anastomotic
      leakage and one rat developed anastomotic obstruction. No anastomotic leakage or
      obstruction was observed in the study group. The burst pressures of the two
      groups were similar. Histology showed that the study group had better alignment
      of the tissue layers and less inflammation compared with the control group.
      CONCLUSIONS: MCT is a safe and feasible technique for colonic anastomosis in
      rats, with better postoperative outcomes compared with hand-sewn anastomosis.

PMID- 30278936
TI  - Does the Surgical Apgar Score predict serious complications after elective major
      cancer surgery?
AB  - BACKGROUND: Major cancer surgery is associated with significant risks of
      perioperative morbidity and mortality, resulting in delayed adjuvant therapy,
      higher recurrence rates, and worse overall survival. Previous retrospective
      studies have used the Surgical Apgar Score (SAS) for perioperative risk
      assessment. This study prospectively evaluated the predictive value of SAS to
      predict serious complication (SC) after elective major cancer surgery. METHODS:
      Demographic, comorbidity, procedure, and intraoperative data were collected
      prospectively for 405 patients undergoing elective major cancer surgery between
      2014-17. The SAS was calculated immediately postoperative and outcome data were
      collected prospectively. Rates of SC according to SAS risk category were compared
      using Cochran-Armitage trend test. Receiver operating characteristic curves and
      area under the receiver operating characteristic curves were generated and 95%
      confidence intervals were calculated. RESULTS: Eighty percent, 17.3%, and 2.7% of
      patients were low (SAS 7-10), intermediate (SAS 5-6), and high risk (SAS 0-4),
      respectively, for SC based on their SAS. Forty-six (11.4%) had an SC within 30
      days; 3.7% returned to the operating room, 3.7% experienced a urinary tract
      infection, 3.2% experienced a respiratory complication, 2.7% experienced a wound
      complication, and 1.2% experienced a cardiac complication. Overall, 9.3%, 18.6%,
      and 27.3% of patients with SAS 7-10, 5-6, and 0-4 experienced an SC, respectively
      (P = 0.005). The overall discriminatory ability of the SAS was modest (area under
      the receiver operating characteristic curves 0.661; 95% confidence intervals,
      0.582-0.740). CONCLUSIONS: Although there was an overall association between SAS
      and higher risk of subsequent postoperative SC in our cohort, the ability of the
      SAS to accurately predict risk of postoperative SC at the patient level was
      limited.

PMID- 30278937
TI  - Perioperative chemotherapy is not associated with improved survival in high-grade
      truncal sarcoma.
AB  - BACKGROUND: The treatment benefit of perioperative chemotherapy (CTX) for truncal
      soft tissue sarcoma (STS) is not well established. This study evaluates the
      association of CTX with survival for patients with resected primary high-grade
      truncal STS. MATERIALS AND METHODS: Adult patients with high-grade truncal STS
      who had curative-intent resection from 2000 to 2016 at seven U.S. institutions
      were evaluated retrospectively. Patients were stratified by receipt of CTX.
      Kaplan-Meier curves with log-rank tests were used to compare overall survival
      (OS) and recurrence-free survival. Logistic regression models were used to
      evaluate characteristics associated with OS. RESULTS: Of patients with primary
      high-grade truncal STS, 235 underwent curative-intent resections. The most common
      histology was undifferentiated pleomorphic sarcoma and mean tumor size was 7.8
      cm. Thirty percent of the patients received CTX (n = 70). Among patients
      receiving CTX, 34% (n = 24) had neoadjuvant CTX, 44% (n = 31) adjuvant CTX, and
      21% (n = 15) had neoadjuvant and adjuvant CTX. Patients receiving CTX were more
      likely to receive radiation (51% versus 34%, P = 0.01), have deep tumors (86%
      versus 73%, P = 0.037) and solid organ invasion (14% versus 3%, P = 0.001). On
      univariate analysis, patients who received CTX had worse OS (P < 0.01) and a
      trend toward worse recurrence-free survival (P = 0.08). Margin status was the
      only variable associated with improved OS on multivariate analysis (odds ratio
      4.36, 95% confidence interval 1.56, 12.13, P < 0.01). CONCLUSIONS: In this multi
      institutional retrospective analysis of resected high-grade truncal STS, receipt
      of perioperative CTX was not associated with improved OS, which may be related to
      selection bias. Microscopically negative margin status was the only independent
      factor associated with OS.

PMID- 30278938
TI  - Can imaging studies be omitted in patients with sporadic primary
      hyperparathyroidism?
AB  - BACKGROUND: The cost-effectiveness of routine preoperative imaging for patients
      undergoing parathyroidectomy is controversial. The purpose of this study is to
      evaluate whether omission of routine preoperative imaging would affect efficiency
      or safety of parathyroidectomy. METHODS: We implemented a no-imaging protocol for
      patients with primary hyperparathyroidism and no prior neck surgery. If the
      patient did not have preoperative parathyroid imaging before evaluation by a
      surgeon, no radiologic studies were ordered, and the patient was scheduled for
      parathyroidectomy. We used propensity matching to address differences between the
      imaging and no-imaging groups. RESULTS: From 2000 to 2015, 83 patients underwent
      parathyroidectomy without imaging compared to 1245 patients with preoperative
      imaging. We successfully matched 64 patients with no preoperative imaging to
      equivalent patients who had imaging prior to surgery. Median age was 60 y, and
      84% were women. There was no significant difference in operative time between
      patients with and without preoperative imaging (84 min for both groups, P <
      0.32). Intraoperative parathyroid hormone levels dropped by at least 50% in all
      patients without preoperative imaging and in 98% of patients with imaging (P <
      0.24). Neither group had recurrences 6 mo after surgery. Overall complication
      rates in the no-imaging (5%) and the imaging group (11%) were also similar (P <
      0.18). CONCLUSIONS: Parathyroid surgery without preoperative imaging is safe,
      effective, and offers equivalent outcomes compared to an approach based on
      routine preoperative imaging. Experienced surgeons can consider omitting
      preoperative imaging in patients without a history of neck surgery as this may
      reduce overall treatment costs.

PMID- 30278939
TI  - Outcomes of surgical intervention for refractory gastroparesis: a systematic
      review.
AB  - BACKGROUND: Gastroparesis (GP) is characterized by delayed gastric emptying with
      symptoms of nausea, vomiting, early satiety, postprandial fullness, and abdominal
      pain. Various surgical options exist to treat GP not responding to medical
      treatments (refractory GP), including gastric electric stimulation (GES),
      gastrectomy (GTx), and pyloric interventions (PI), whereas the outcomes of these
      procedures have been published; few comparison studies exist. METHODS: PubMed
      literature review for articles from September 1988 to October 2017 was performed
      for prospective and retrospective analyses reporting >5 patients. Unweighted (per
      study) and weighted (per patient) overall improvement and improvement in symptoms
      of nausea, vomiting, and abdominal pain were calculated and compared for the
      different procedures. RESULTS: Of 325 studies satisfying search criteria, 38 met
      the study criteria and were included for analysis. Total response to
      intervention, both weighted and unweighted, was greater with PIs compared to GES
      (P < 0.05). For unweighted symptom improvements, nausea improved more with PI
      than with GES (P < 0.05). GES improved vomiting more than epigastric pain (P <
      0.05). For weighted symptom improvements, pyloric surgery and GTx improved
      vomiting compared to GES (P < 0.05). CONCLUSIONS: Published outcomes of GES,
      pyloric surgery, and GTx for refractory GP are compared.
      Pyloromyotomy/pyloroplasty improves patient response greater than with GES.
      Weighing by number of studies, pyloric surgery improves nausea and abdominal pain
      greater than GES. For GES, vomiting is more likely to improve than abdominal
      pain. Weighing by number of patients, pyloric surgery and GTx improved vomiting
      compared to GES.

PMID- 30278940
TI  - Toll-like receptor activation as a biomarker in traumatically injured patients.
AB  - BACKGROUND: Surgical insult and trauma have been shown to cause dysregulation of
      the immune and inflammatory responses. Interaction of damage-associated molecular
      patterns (DAMPs) with toll-like receptors (TLRs) initiates innate immune response
      and systemic inflammatory responses. Given that surgical patients produce high
      levels of circulating damage-associated molecular patterns, we hypothesized that
      plasma-activated TLR activity would be correlated to injury status and could be
      used to predict pathological conditions involving tissue injury. METHODS: An
      observational study was performed using samples from a single-institution
      prospective tissue and data repository from a Level-1 trauma center. In vitro TLR
      2, 3, 4, and 9 activation was determined in a TLR reporter assay after isolation
      of plasma from peripheral blood. We determined correlations between plasma
      activated TLR activity and clinical course measures of severity. RESULTS:
      Eighteen patients were enrolled (median Injury Severity Score 15 [interquartile
      range 10, 23.5]). Trauma resulted in significant elevation in circulation high
      mobility group box 1 as well as increase of plasma-activated TLR activation (2.8
      5.4-fold) compared to healthy controls. There was no correlation between
      circulating high mobility group box 1 and trauma morbidity; however, the plasma
      activated TLR activity was correlated with acute physiology and chronic health
      evaluation II scores (R square = 0.24-0.38, P < 0.05). Patients who received
      blood products demonstrated significant increases in the levels of plasma
      activated TLRs 2, 3, 4, and 9 and had a trend toward developing systemic
      inflammatory response syndrome. CONCLUSIONS: Further studies examining TLR
      modulation and signaling in surgical patients may assist in predictive risk
      modeling and reduction in morbidity and mortality.

PMID- 30278941
TI  - Hepatic topographical changes of endoplasmic reticulum stress and unfolded
      protein response signaling after hemorrhagic shock and reperfusion.
AB  - BACKGROUND: Endoplasmic reticulum (ER) stress plays a crucial role in cell death
      decisions in context of various diseases. Although it is known that ER stress
      occurs in livers subjected to hemorrhagic shock and reperfusion (HS/R), there is
      no understanding about the influence of the liver architecture on ER stress and
      the activation of the unfolded protein response (UPR). MATERIALS AND METHODS:
      Mice were subjected to a pressure-controlled HS (30 +/- 5 mmHg) for 90 min. Mice
      were sacrificed 2, 4, 6, 8, 10, 14, 18, and 24 h after shock induction. Plasma
      levels of inflammatory cytokines (IL-6, CXCL1, CXCL9, CXCL10, CCL2, CCL3) and
      transaminases were measured. Hematoxylin and eosin stains of paraffin-embedded
      liver tissue sections were evaluated for liver damage. Immunohistochemistry was
      used to analyze the hepatic topography of ER stress marker binding immunoglobulin
      protein and the activation of the three major pathways of the UPR. RESULTS:
      Compared with sham-operated mice, HS/R led to profound liver damage and an
      elevation of inflammatory cytokines. We found time-dependent topographical
      changes of ER stress in the livers. Furthermore, the three major pathways of the
      UPR represented by protein kinase RNA-like ER kinase, activating transcription
      factor 6, and inositol-requiring enzyme 1 were activated in differing ways
      dependent on the zonation within the liver acinus. CONCLUSIONS: These findings
      show that the liver architecture must be taken into account when investigating
      the role of ER stress and the UPR in ischemia-reperfusion injury after HS/R.

PMID- 30278942
TI  - Implant volume estimation in direct-to-implant breast reconstruction after nipple
      sparing mastectomy.
AB  - BACKGROUND: Nipple-sparing mastectomy (NSM) is an increasingly popular
      alternative to more traditional mastectomy approaches. However, estimating the
      implant volume during direct-to-implant (DTI) reconstruction following NSM is
      difficult for surgeons with little-to-moderate experience. We aimed to provide a
      fast, easy to use, and accurate method to aid in the estimation of implant size
      for DTI reconstruction using the specimen weight and breast volume. METHODS: A
      retrospective analysis was performed using data from 145 NSM patients with
      specific implant types. Standard two-dimensional digital mammograms were obtained
      in 118 of the patients. Breast morphological factors (specimen weight,
      mammographic breast density and volume, and implant size and type) were recorded.
      Curve-fitting and linear regression models were used to develop formulas
      predicting the implant volume, and the prediction performance of the obtained
      formulas was evaluated using the prospective data set. RESULTS: Two formulas to
      estimate the implant size were obtained, one using the specimen weight and one
      using the breast volume. The coefficients of correlation (R2) in these formulas
      were over 0.98 and the root mean squared errors were approximately 13.
      CONCLUSIONS: These implant volume estimate formulas benefit surgeons by providing
      a preoperative implant volume assessment in DTI reconstruction using the breast
      volume and an intraoperative assessment using the specimen weight. The implant
      size estimation formulas obtained in the present study may be applied in a
      majority of patients.

PMID- 30278943
TI  - Fluorescence imaging-guided robotic thyroidectomy and central lymph node
      dissection.
AB  - BACKGROUND: The purpose of this study was to evaluate the feasibility of complete
      central compartment node dissection (CCND) using fluorescence imaging (FI) during
      robotic thyroidectomy. METHODS: A total of 110 patients underwent robotic
      thyroidectomy and CCND from August 2015 to June 2016; 55 patients underwent
      robotic surgery using FI (FI group) and the other 55 patients without it (control
      group). The FI group was injected with indocyanine green into the thyroid to
      enhance the identification of lymph nodes (LNs). RESULTS: Indocyanine green
      stained LNs were easily detected using FI. The number of harvested LNs was 7.0 in
      the FI group and 4.8 in the control group (P = 0.004). There was lower rate of
      transient hypocalcemia in the FI group (18.5%) than control group (26.7%), but
      there was no significant difference (P = 0.417). There were no other significant
      differences between the two groups. CONCLUSIONS: The use of FI during robotic
      thyroidectomy facilitated the identification of LNs and guided complete CCND.

PMID- 30278944
TI  - Preventive role of superoxide dismutase on radiation-induced periprosthetic
      capsule development.
AB  - BACKGROUND: Capsule fibrosis is the most important and annoying complication of
      breast implant surgery. Radiotherapy (RT) used in the local treatment of breast
      cancer has an increasing effect on the existing fibrous capsule; this is called
      radiation-induced fibrosis (RIF). In this randomized controlled experimental
      study, we aim to investigate the reduction effect of superoxide dismutase (SOD)
      on RIF. METHODS: Sprague-Dawley rats were randomized into four groups, all of
      which were subjected to implant surgery. No additional procedures were done for
      the control group. The other groups were the SOD group, the RT + SOD group, and
      the RT group. The capsules were evaluated histopathologically. RESULTS: Although
      SOD reduced surgery-induced capsule formation, it neither prevented nor reduced
      significantly RIF. CONCLUSIONS: In an experimental model that resembled breast
      cancer treatment, we concluded that SOD cannot reduce RIF but is effective in
      reducing capsular fibrosis around the silicone after implant surgery.

PMID- 30278945
TI  - Mortality after pancreaticoduodenectomy: assessing early and late causes of
      patient death.
AB  - BACKGROUND: Safety of pancreaticoduodenectomy has improved significantly in the
      past 3 decades. Current inpatient and 30-d mortality rates are low. However,
      incidence and causes of 90-d and 1-y mortality are poorly defined and largely
      unexplored. METHODS: All patients who had pancreaticoduodenectomy between 2007
      and 2016 were included in this single institution, retrospective cohort study.
      Distributions of pancreaticoduodenectomy-specific morbidity and cause-specific
      mortality were compared between early (within 90 d) and late (91-365 d)
      postoperative recovery periods. RESULTS: A total of 551 pancreaticoduodenectomies
      were performed during the study period. Of these, 6 (1.1%), 20 (3.6%), and 91
      (16.5%) patients died within 30, 90, and 365 d after pancreaticoduodenectomy,
      respectively. Causes of early and late mortality varied significantly (all P <=
      0.032). The most common cause of death within 90 d was due to multisystem organ
      failure from sepsis or aspiration in 9 (45%) patients, followed by post
      pancreatectomy hemorrhage in 5 (25%) patients, and cardiopulmonary arrest from
      myocardial infarction or pulmonary embolus in 3 (15%) patients. In contrast,
      recurrent cancer was the most common cause of death in 46 (65%) patients during
      the late postoperative period between 91 and 365 d. Mortality from failure to
      thrive and debility was similar between early and late postoperative periods (15%
      versus 19.7%, P = 0.76). CONCLUSIONS: Most quality improvement initiatives in
      patients selected for pancreaticoduodenectomy have focused on reduction of
      technical complications and improvement of early postoperative mortality. Further
      reduction in postoperative mortality after pancreaticoduodenectomy can be
      achieved by improving patient selection, mitigating postoperative malnutrition,
      and optimizing preoperative cancer staging and management strategies.

PMID- 30278946
TI  - Postoperative urinary retention after laparoscopic total extraperitoneal inguinal
      hernia repair.
AB  - BACKGROUND: Postoperative urinary retention (POUR) after laparoscopic inguinal
      hernia repair has an incidence of 2%-30%. POUR can lead to increased length of
      stay, decreased patient satisfaction, and increased health-care costs. The
      objective of this study was to determine the patient risk factors at our
      institution contributing to POUR after laparoscopic total extraperitoneal (TEP)
      inguinal hernia repair. METHODS: A retrospective chart review of patients who
      underwent a laparoscopic TEP inguinal hernia repair at our institution from 2009
      to 2016. POUR is defined as the inability to urinate requiring urinary straight
      or indwelling catheterization in the postoperative period. Univariate analyses
      were performed on perioperative variables and their correlation with POUR.
      RESULTS: In total, 578 laparoscopic TEP inguinal hernia repair patients were
      included in the study: 277 (48%) indirect, 144 (25%) direct, 6 (1%) femoral, and
      151 (26%) combination of direct, indirect, and/or femoral hernias. Of these, 292
      (51%) were bilateral, and 286 (49%) were unilateral. Overall, 64 (11.1%) of the
      578 patients developed POUR. POUR was significantly associated with benign
      prostatic hyperplasia, age 60 y or older, urinary tract infection within 30 d,
      and decreased body mass index. CONCLUSIONS: Patients aged greater than 60 y, with
      benign prostatic hyperplasia, and a decreased body mass index (<=25.8 kg/m2) were
      more likely to develop POUR after laparoscopic TEP inguinal hernia repair. In
      addition, these patients were more likely to develop a urinary tract infection
      within 30 d. Future quality initiatives can be explored to minimize the incidence
      of POUR in high-risk patient populations.

PMID- 30278947
TI  - Autologous fat grafting to lumpectomy defects: complications, imaging, and biopsy
      rates.
AB  - BACKGROUND: Autologous fat grafting is emerging as a promising reconstructive
      technique after breast conservation therapy (BCT). Recent evidence suggests that
      autologous fat grafting does not increase the risk of cancer recurrence; however,
      women may still be subject to unnecessary biopsies secondary to suspicious
      radiologic findings. The purpose of this study was to assess surgical
      complications and biopsy rates in these patients. METHODS: We retrospectively
      reviewed the records of women who underwent autologous fat grafting after BCT at
      a single institution over a 6-y period. Independent variables included
      demographic and operative details. Outcome variables included complications, and
      incidence of palpable masses and/or suspicious breast imaging findings requiring
      biopsy. Descriptive statistics were generated. RESULTS: Between June 2008 and
      February 2015, 37 women aged 41 to 74 y (mean 54.4 y) underwent a total of 56 fat
      grafting sessions for correction of contour deformities after BCT. The mean
      number of fat grafting procedures was 1.5 (range 1-4) per breast. Follow-up
      ranged from 1 to 99 mo (mean 29.5 mo). Imaging data were available for 31 (83.7%)
      breasts after autologous fat grafting. Biopsy was recommended in four cases after
      suspicious imaging findings or palpable masses (10.8%), with benign pathology in
      all cases. There was one incidence of a local wound infection. No other local or
      systemic complications were noted. CONCLUSIONS: Our study demonstrated a risk of
      unnecessary biopsies after autologous fat grafting. Complication rates were low,
      and it appears to be a safe reconstructive option for the correction of contour
      deformities after BCT.

PMID- 30278948
TI  - Upregulation of phosphorylated sphingosine kinase 1 expression in colitis
      associated cancer.
AB  - BACKGROUND: Colitis-associated cancer (CAC) is the most serious complication of
      inflammatory bowel disease. Sphingosine-1-phosphate (S1P) is a bioactive lipid
      mediator that is generated by sphingosine kinase 1 (SphK1) and is known to play
      an important role in inflammation and cancer progression. Moreover, SphK1 and S1P
      act as upstream mediators of proinflammatory cytokine interleukin 6 (IL-6) and
      signal transducer and activator of transcription-3 (STAT3). We hypothesized that
      the expression levels of phosphorylated SphK1 (pSphK1), phosphorylated STAT3
      (pSTAT3), and IL-6 are universally higher in CAC patients than in sporadic
      colorectal cancer (CRC) patients because all of these factors are associated with
      inflammation. In this study, we determined the expression levels of pSphK1 in
      patients with sporadic CRC and CAC and clarified the importance of S1P in CAC
      patients. MATERIALS AND METHODS: We randomly selected 10 sporadic CRC patients
      and 10 CAC patients who underwent curative resection, and we examined their
      surgical specimens by immunohistochemistry. We determined the expression levels
      of pSphK1, pSTAT3, and IL-6 in these samples. RESULTS: We found pSphK1 expression
      to be more prevalent in CAC patients (P = 0.019) and to have a higher
      immunohistochemistry score (P = 0.005) than in sporadic CRC patients. However,
      the expression of pSTAT3 and IL-6 did not differ between the patient groups.
      CONCLUSIONS: To our knowledge, this is the first report comparing pSphK1
      expression levels in CAC with those in sporadic CRC. The high levels of pSphK1
      expression in CAC suggest an important role of S1P in the disease process of CAC.

PMID- 30278949
TI  - Mucosal homeostasis is altered in the ileum of gnotobiotic mice.
AB  - BACKGROUND: The microbiome of the gastrointestinal tract is a vast collection of
      microorganisms implicated in numerous aspects of normal physiology and disease
      pathogenesis. The use of gnotobiotic mouse models, with single or specific
      communities of microbes comprising the microbiome, can enhance our understanding
      of the microbiome-host relationship. We hypothesized that gnotobiotic mice would
      exhibit differences in mucosal homeostasis when compared with mice with
      conventional flora (CF). MATERIALS AND METHODS: Single-organism gnotobiotic mice
      were generated containing Escherichia coli MG1655, Akkermansia muciniphila,
      Bacteroides eggerthii, and Clostridium symbiosum, representing four of the major
      phyla present in the gastrointestinal tract. Distal ileal segments were harvested
      from adult mice, and histologic sections were H&E stained and used to measure
      villus height and crypt depth. Immunohistochemistry was performed with Ki67 and
      TUNEL as markers of proliferation and apoptosis, respectively. RESULTS: When
      compared to the ileum from CF mice, the ileum from all groups of gnotobiotic mice
      had significant increases in nearly all measured parameters. In addition,
      significant differences were seen among certain gnotobiotic groups for villus
      height, crypt depth, and apoptosis. CONCLUSIONS: Single-organism gnotobiotic mice
      demonstrate enhanced morphometric parameters compared with mice with CF and show
      differences in growth patterns among bacterial species. These findings suggest
      unique interactions between individual bacteria and the host animal which hold
      potential for future therapeutic strategies aimed at mucosal restoration. The
      mechanisms involved in this process therefore warrant further study.

PMID- 30278950
TI  - Prognostic impact of elevated preoperative C-reactive protein on patients with
      differentiated thyroid carcinoma.
AB  - BACKGROUND: C-reactive protein (CRP) has been reported to be associated with
      poorer prognosis in various malignancies. However, the relationship between CRP
      and differentiated thyroid carcinoma (DTC) remains to be elucidated. METHODS: A
      total of 45 patients, including 32 patients with preoperative DTC and 13 DTC
      patients with metastatic disease, were included in the study. The relationships
      between CRP levels and clinicopathological features were retrospectively
      analyzed. RESULTS: Analysis using a receiver operating characteristic curve
      revealed a preoperative CRP cutoff value of 0.155 mg/dL. Patients with
      preoperative CRP >= 0.155 mg/dL, those with T3 + T4, those with extrathyroidal
      invasion, or those with stage II, showed a statistically shorter recurrent-free
      survival than those with preoperative CRP < 0.155 mg/dL, those with T1 + T2,
      those without extrathyroidal invasion, or those with stage I (P = 0.001, P =
      0.004, P = 0.024, and P = 0.025, respectively). Preoperative CRP >= 0.155 mg/dL
      was an independent prognostic factor for recurrent-free survival in the DTC
      patients (hazard ratio = 6.334, 95% confidence interval: 1.023-39.234, P =
      0.037). The proportion of patients aged >=55 y, and those with T3 + T4, was
      statistically higher in those with preoperative CRP >= 0.155 mg/dL than in those
      with preoperative CRP < 0.155 mg/dL (P = 0.037 and P = 0.038, respectively).
      CONCLUSIONS: Higher preoperative CRP levels have a robust prognostic impact on
      recurrence-free survival in DTC patients. In addition, higher preoperative CRP
      levels were associated with age >= 55 y and T3 + T4.

PMID- 30278951
TI  - Tunneled central venous catheters in pediatric intestinal failure: a single
      center experience.
AB  - BACKGROUND: Parenteral nutrition for intestinal failure (IF) often requires a
      tunneled central venous catheter (CVC). The purpose of this study was to
      characterize complications after CVC placement and contributors to line loss in
      pediatric IF patients. METHODS: An institutional review board-approved
      retrospective review of pediatric (<18 y) IF patients who had a silicone tunneled
      CVC newly inserted or exchanged from 2012 to 2016 in an IF center was conducted.
      Patient demographics, procedure service (surgery versus interventional
      radiology), procedure type (new versus exchange), vessel, and complications
      related to CVCs were evaluated. Complications included dislodgement, infection,
      break, occlusion/malfunction, and others. An ethanol-lock protocol for silicone
      CVCs in IF patients was instituted in January 2012. RESULTS: Twenty-nine IF
      patients with tunneled CVCs were identified with 182 lines and 18,534 line d.
      Median age at line insertion was 17.1 mo (interquartile range [IQR] 7.6-31.5)
      with a median of five catheters (IQR 2-8) per patient. There were 19.2
      complications per 1000 line d. Occlusions/malfunctions were the most common
      complication (6.0/1000 line d) followed by breaks (5.6/1000 line d). Median life
      of catheters was 51.5 d (IQR 21-129). On regression, adjusting for age, insertion
      service, and procedure type, shorter line life was associated with younger age (P
      = 0.04) and placement by interventional radiology (P < 0.01). Dislodgement was
      associated with newly placed lines relative risk 6.5 (95% CI 2.2-28.8).
      CONCLUSIONS: CVCs in pediatric IF patients have frequent complications and short
      line lifetimes. Dislodgement of CVC was an unexpectedly common complication with
      loss of access in newly placed lines. There may be modifiable processes to
      mitigate CVC complications.

PMID- 30278952
TI  - A population-based analysis of outcomes after repair of thoracic aortic
      emergencies in trauma.
AB  - BACKGROUND: Large-scale assessments of outcomes in thoracic endovascular repair
      (TEVAR) for thoracic aortic emergencies are lacking. We evaluated perioperative
      outcomes of TEVAR compared with open surgery among trauma patients in a large
      statewide database. MATERIALS AND METHODS: We evaluated the California Office of
      Statewide Health Planning and Development 2007-2014 patient discharge database.
      Blunt-injured trauma patients with thoracic aortic emergencies were identified by
      International Classification for Diseases, Ninth Revision, Clinical Modification
      diagnosis codes and external cause-of-injury codes. Procedure codes were
      evaluated for TEVAR or open repair. Outcomes included mortality or complications
      during the index admission and readmission within 30 d. The association between
      both operative methods and each outcome was evaluated by two-level logistic
      regression adjusting for age, length of stay, admission year, trauma-related
      mortality probability, and comorbidity status. RESULTS: Among over 31 million
      hospitalizations, we identified 48,357 cases (0.2%) of thoracic aortic disease.
      Of these, 2159 (4.5%) were unique blunt-injured trauma patients of whom 336
      (15.6%) underwent operative repair: 256 TEVAR (76.2%) and 80 (23.8%) open repair.
      Patients with open repair were older than TEVAR patients (mean age 52.0 versus
      46.8, P = 0.038). There were no significant differences in race, sex, injury
      mechanism, mortality, or 30-d readmission by operative method. However, open
      repair was associated with greater odds for cardiac, spinal cord, and
      neurological complications. CONCLUSIONS: Although mortality in trauma patients
      who underwent TEVAR was similar to that in patients with open repair, TEVAR was
      associated with fewer complications. This suggests that TEVAR offers clinical
      benefit over open repair in treating trauma patients with aortic disease.

PMID- 30278953
TI  - Treatment patterns for ductal carcinoma in situ with close or positive mastectomy
      margins.
AB  - BACKGROUND: Mastectomy remains an effective treatment for ductal carcinoma in
      situ (DCIS) but whether further therapy is warranted for close or positive
      margins is controversial. We aim to characterize the treatment practices of DCIS
      throughout the United States in patients who undergo mastectomy with close or
      positive margins to better understand the use of postmastectomy radiation therapy
      (PMRT). MATERIALS AND METHODS: Using the 2004-2013 National Cancer Database, we
      identified all female patients with a diagnosis of DCIS who underwent mastectomy.
      Distributional characteristics were summarized for overall and margin-stratified
      samples. Characteristic differences were assessed by region and receipt of
      radiation. Chi-square and independent sample t-tests were used to assess
      differences for categorical and continuous variables, respectively. RESULTS: In
      21,591 patients who met inclusion criteria, 470 patients with close/positive
      margins were identified. Sixteen percent of patients with close/positive margins
      received PMRT compared to 1.5% with negative margins (P < 0.01). There was no
      difference in PMRT and patient race, insurance status, treatment facility, or
      endocrine therapy. Patients with close/positive margins who received PMRT were
      more likely to be in an urban setting from the Midwest (24.6%) and Northeast
      (21.8%) compared to the West (11.0%) and South (10.7%) (P < 0.01). CONCLUSIONS:
      Use of PMRT for DCIS following mastectomy with close/positive margins differs
      across the country. Regional variations in treatment patterns reinforce a need to
      determine whether PMRT improves survival to establish treatment guidelines.

PMID- 30278954
TI  - Fetal intervention for congenital chylothorax is associated with improved
      outcomes in early life.
AB  - BACKGROUND: Congenital chylothorax (CC) can have devastating consequences for
      neonates. We sought to determine the outcomes of cases treated at our institution
      and evaluate the role of fetal intervention. MATERIALS AND METHODS: With
      Institutional Review Board approval, patients treated at our institution 09/2006
      04/2016 with CC were reviewed. History and outcomes were compared between
      patients undergoing fetal intervention (fetal group) and patients who did not
      (control group). RESULTS: Twenty-three patients were identified. Mean gestational
      age at birth was 35 wk. Overall mortality was 30% (7 patients). Nineteen patients
      (83%) were prenatally diagnosed, and 10 patients (43%) underwent fetal
      intervention. Birth weight was significantly lower in the fetal group compared to
      the control group (median interquartile range [IQR]; 2.5 [2.3-3.0] versus 3.3
      [2.6-3.7] kg, P = 0.02). Apgar scores were significantly higher in the fetal
      group than the control group at 1 and 5 min (median [IQR]; 6 [4-8] versus 1 [1
      2], P = 0.005 and 8 [7-9] versus 2 [2-6], P = 0.008, respectively). For those
      patients with prenatal diagnosis of CC and hydrops fetalis, thrombosis and
      lymphopenia were both improved in the fetal group (thrombosis 0% versus 40%, P =
      0.03; lymphocyte nadir [median {IQR}] 1.5 [0.6-2.9] versus 0.1 [0.05-0.2], P =
      0.02). Duration of support with mechanical ventilation was significantly shorter
      in the fetal group (median [IQR]; 1 [0-40] versus 41 [29-75] d, P = 0.04).
      CONCLUSIONS: Fetal intervention for CC is associated with improved Apgar scores
      and decreased ventilator days and complications in patients with hydrops fetalis.
      Fetuses with chylothorax, especially those with hydrops, should be referred to a
      fetal center for evaluation.

PMID- 30278955
TI  - Postischemic application of estrogen ameliorates myocardial damage in an in vivo
      mouse model.
AB  - BACKGROUND: Cardioprotection provided by estrogen has been recognized for many
      years. It is noteworthy that most of these studies employ a means of preinjury
      application in experimental research and the preventive usage in clinical
      studies. Compared to pretreatment, postischemic administration of estrogen will
      be more practical in treating myocardial ischemia. On the other hand, defect in
      circadian clock gene period2 (Per2) has been shown to aggravate ischemia-induced
      heart damage. Given that Per2 expression decreases as a consequence of menopause,
      in this study, we aim to determine (1) potential improvement of myocardial
      function by postischemic administration of 17beta-estradiol (E2) using an in vivo
      mouse myocardial ischemia/reperfusion (I/R) model and (2) the role of E2 in
      regulating myocardial Per2 expression following I/R. METHODS: Thirty-minute
      occlusion of left anterior descending artery followed by 24-h reperfusion was
      performed on adult C57BL ovariectomized female mice. Groups (n = 3-6/group) were
      as follows: (1) Sham, (2) I/R + vehicle, and (3) I/R + E2. Vehicle or 0.5 mg/kg
      of E2 was subcutaneously injected right after 30-min ischemia. Following 24-h
      reperfusion, myocardial function was determined. Heart tissue was collected for
      analysis of cleaved caspase-3 and Per2 expression by Western blotting, as well as
      proinflammatory cytokine production (IL-1beta, IL-6, and TNF-alpha) by enzyme
      linked immunosorbent assay. RESULTS: I/R significantly impaired left ventricular
      function and increased myocardial levels of active caspase-3, IL-1beta, and IL-6.
      Importantly, postischemic treatment of E2 markedly restored I/R-depressed
      myocardial function, reduced caspase-3 activation, and decreased proinflammatory
      cytokine production (IL-1beta, IL-6, and TNF-alpha). Intriguingly, a trend of the
      decreased Per2 level was observed in ovariectomized female hearts subjected to
      I/R, whereas E2 treatment upregulated myocardial Per2 expression. CONCLUSIONS:
      Our study represents the initial evidence that postischemic administration of E2
      effectively preserves the myocardium against I/R injury and this protective
      effect of E2 may involve upregulation of Per2 in ischemic heart.

PMID- 30278956
TI  - Sooner is better: use of a real-time automated bedside dashboard improves sepsis
      care.
AB  - BACKGROUND: Minimizing the interval between diagnosis of sepsis and
      administration of antibiotics improves patient outcomes. We hypothesized that a
      commercially available bedside clinical surveillance visualization system (BSV)
      would hasten antibiotic administration and decrease length of stay (LOS) in
      surgical intensive care unit (SICU) patients. METHODS: A BSV, integrated with the
      electronic medical record and displayed at bedside, was implemented in our SICU
      in July 2016. A visual sepsis screen score (SSS) was added in July 2017. All
      patients admitted to SICU beds with bedside displays equipped with a BSV were
      analyzed to determine mean SSS, maximum SSS, time from positive SSS to antibiotic
      administration, SICU LOS, and mortality. RESULTS: During the study period, 232
      patients were admitted to beds equipped with the clinical surveillance
      visualization system. Thirty patients demonstrated positive SSS followed by
      confirmed sepsis (23 Pre-SSS versus 7 Post-SSS). Mean and maximum SSS were
      similar. Time from positive SSS to antibiotic administration was decreased in
      patients with a visual SSS (55.3 +/- 15.5 h versus 16.2 +/- 9.2 h; P < 0.05). ICU
      and hospital LOS was also decreased (P < 0.01). CONCLUSIONS: Implementation of a
      visual SSS into a BSV led to a decreased time interval between the positive SSS
      and administration of antibiotics and was associated with shorter SICU and
      hospital LOS. Integration of a visual decision support system may help providers
      adhere to Surviving Sepsis Guidelines.

PMID- 30278957
TI  - A preoperative prediction model for risk of multiple admissions after colon
      cancer surgery.
AB  - BACKGROUND: A subset of patients who undergo colon cancer surgery may be at a
      high risk of multiple subsequent admissions. We developed a simplified model to
      predict the preoperative risk of multiple postoperative admissions (MuAdm) among
      patients undergoing colon resection to aid in preoperative planning. METHODS:
      Patients aged >=18 y with colon cancer who underwent elective surgical resection
      identified in discharge claims from California and New York (2008-2011) were
      included. The primary outcome, MuAdm, was defined as 2 or more admissions in the
      year following resection. Logistic regression models were developed to identify
      factors predictive of MuAdm. A weighted point system was developed using beta
      coefficients (P < 0.05). A random sample of 75% of the data was used for model
      development, which was validated in the remaining 25% sample. RESULTS: A total of
      14,780 patients underwent colon resection for cancer. Almost 30% had an admission
      in the year after index surgery and 9.8% had MuAdm. The significant predictors of
      MuAdm were higher Elixhauser comorbidity index score, metastatic disease, payer
      system, and the number of admissions in the year before surgery. Scores ranged
      from 0 to 8. Scores <=1 had a 7% risk of MuAdm, and scores >=6 had a >30% risk of
      MuAdm. CONCLUSIONS: In the year following discharge after resection of colon
      cancer, nearly 10% of patients are admitted 2 or more times. A simple,
      preoperative clinical model can prospectively predict the likelihood of multiple
      admissions in patients anticipating resection. This model can be used for
      preoperative planning and setting postoperative expectations more accurately.

PMID- 30278959
TI  - Improved survival in simultaneous lung-liver recipients and candidates in the
      modern era of lung allocation.
AB  - BACKGROUND: Liver-lung transplantation (LLT) is a rare procedure performed for
      patients with end-stage liver and lung disease. The lung allocation score (LAS),
      introduced in 2005, guides lung allocation including those receiving LLT.
      However, the impact of the LAS on outcomes in LLT is currently unknown. MATERIALS
      AND METHODS: The OPTN/United Network for Organ Sharing STAR file was queried for
      LLT candidates and recipients from 1988 to 2016. Demographic characteristics
      before (historic) and after (modern) the LAS were compared. Survival was analyzed
      with the Kaplan-Meier method and log-rank test. RESULTS: In total, 167 candidates
      were listed for LLT, and 62 underwent LLT. The historic cohort had a higher FEV1%
      (48.22% versus 29.82%, P = 0.014), higher creatinine (1.22 versus 0.72, P <
      0.001), and a higher percentage with pulmonary hypertension as the indication for
      transplantation (40% versus 0%, P = 0.003) compared with the modern cohort. LLT
      candidates in the historic cohort had a lower rate of transplant per 100
      candidates (10.87 versus 33.33, P < 0.0001) and worse waitlist survival (1 y:
      69.6% versus 80.9%, 3 y: 39.1% versus 66.8%, P = 0.004). Post-transplant survival
      was significantly lower in the historic cohort (1 y: 50.0% versus 82.7%, 5 y:
      40.0% versus 69.0%, 10 y: 20.0% versus 55.5%, P = 0.0099). CONCLUSIONS: Most
      analyses of LLT have included patients before and after the introduction of the
      LAS. Our study shows that LLT candidates and recipients before the modern
      allocation system had distinct baseline characteristics and worse overall
      survival. Although many factors contributed to recent improved outcomes, these
      cohorts are significantly different and should be treated as such in future
      studies.

PMID- 30278958
TI  - Are we overtreating intraductal papillomas?
AB  - BACKGROUND: The management of intraductal papillomas (IDPs) diagnosed on core
      needle biopsy (CNB) remains controversial regarding whether excision is required.
      We evaluated whether excision of IDPs might be overtreatment based on a
      consecutive patient population where all IDPs were routinely excised. MATERIALS
      AND METHODS: We retrospectively reviewed the records of consecutive patients
      treated with excision of IDPs at our institution from 2009 to 2016. We evaluated
      the rate of upgrade of IDPs on CNB and factors predicting for malignant upgrade.
      RESULTS: Of 153 CNB specimens, 136 (88.9%) were IDPs without atypia and 14 (9.2%)
      showed atypia. The overall upgrade rate on final pathology was 7.3% with 1.3% for
      invasive cancer, 2.7% for ductal carcinoma in situ, and 3.3% for atypical ductal
      hyperplasia. Of the 14 patients with atypia on CNB, two of these patients (14.2%)
      were found to have ductal carcinoma in situ. In the absence of atypia on CNB,
      upgrade rates were 1.5% for invasive and 1.5% for in situ carcinoma. Personal
      history of breast cancer and magnetic resonance imaging-guided biopsy predicted
      for malignant upgrade. CONCLUSIONS: IDPs on CNB have a low chance of harboring an
      occult malignancy. Given the low probability of upgrade to invasive breast
      cancer, it is reasonable to consider watchful surveillance in the absence of a
      prior personal history of breast cancer or atypia on CNB.

PMID- 30278960
TI  - Gamma-glutamyl transpeptidase to platelet ratio predicts short-term outcomes in
      hepatocellular carcinoma patients undergoing minor liver resection.
AB  - BACKGROUND: There is a strong correlation between liver fibrosis and
      postoperative morbidity after hepatectomy in hepatocellular carcinoma (HCC)
      patients. The aim of this study was to evaluate which noninvasive fibrosis index
      (gamma-glutamyl transpeptidase to platelet ratio [GPR], aspartate
      aminotransferase to platelet ratio index, fibrosis-4 index, or Forns index) was
      best able to predict complications in patients undergoing hepatectomy for HCC.
      MATERIALS AND METHODS: This retrospective analysis included 275 patients who
      underwent hepatectomy for HCC from January 2008 to December 2012. Postoperative
      mortality was defined as death within 90 d after surgery. Complications were
      grouped into seven grades on the basis of the modified Clavien classification,
      and major postoperative complications were defined as grade 3 or above. The
      influence of noninvasive fibrosis indices on postoperative outcomes was assessed
      by receiver operating characteristic analysis. The primary outcomes were overall
      complications and major complications, estimated by univariate and multivariate
      analysis. RESULTS: Patients with HCC undergoing anatomical liver resection in the
      authors' department were evaluated for this study. Finally, 275 patients who
      underwent minor liver resection (<=2 liver segments) were included. Of these, 231
      (84%) were male. The multivariate analysis indicated that the GPR index was not
      only independently associated with overall complications (hazard ratio, 2.692;
      95% confidence interval [CI], 1.626-4.250; P < 0.001) but also independently
      predictive of major complications (hazard ratio, 1.143; 95% CI, 1.046-1.249; P =
      0.03). The areas under the receiver operating characteristic curve for predicting
      overall complications and major complications for the GPR index were 0.704 (95%
      CI, 0.643-0.765; P < 0.001) and 0.752 (95% CI, 0.638-0.865; P < 0.001),
      respectively. CONCLUSIONS: The data suggested that the GPR index could be a
      promising predictor of overall postoperative complications and major
      complications after minor hepatectomy for HCC.

PMID- 30278961
TI  - Fetal lung transcriptome patterns in an ex vivo compression model of
      diaphragmatic hernia.
AB  - BACKGROUND: The purpose of this study was to employ a novel ex vivo lung model of
      congenital diaphragmatic hernia (CDH) to determine how a mechanical compression
      affects early pulmonary development. METHODS: Day-15 whole fetal rat lungs (n = 6
      12/group) from nitrofen-exposed and normal (vehicle only) dams were explanted and
      cultured ex vivo in compression microdevices (0.2 or 0.4 kPa) for 16 h to mimic
      physiologic compression forces that occur in CDH in vivo. Lungs were evaluated
      with significance set at P < 0.05. RESULTS: Nitrofen-exposed lungs were
      hypoplastic and expressed lower levels of surfactant protein C at baseline.
      Although compression alone did not alter the alpha-smooth muscle actin (ACTA2)
      expression in normal lungs, nitrofen-exposed lungs had significantly increased
      ACTA2 transcripts (0.2 kPa: 2.04 +/- 0.15; 0.4 kPa: 2.22 +/- 0.11; both P <
      0.001). Nitrofen-exposed lungs also showed further reductions in surfactant
      protein C expression at 0.2 and 0.4 kPa (0.53 +/- 0.04, P < 0.01; 0.69 +/- 0.23,
      P < 0.001; respectively). Whereas normal lungs exposed to 0.2 and 0.4 kPa showed
      significant increases in periostin (POSTN), a mechanical stress-response molecule
      (1.79 +/- 0.10 and 2.12 +/- 0.39, respectively; both P < 0.001), nitrofen-exposed
      lungs had a significant decrease in POSTN expression (0.4 kPa: 0.67 +/- 0.15, P <
      0.001), which was confirmed by immunohistochemistry. CONCLUSIONS: Collectively,
      these pilot data in a model of CDH lung hypoplasia suggest a primary aberration
      in response to mechanical stress within the nitrofen lung, characterized by an
      upregulation of ACTA2 and a downregulation in SPFTC and POSTN. This ex vivo
      compression system may serve as a novel research platform to better understand
      the mechanobiology and complex regulation of matricellular dynamics during CDH
      fetal lung development.

PMID- 30278962
TI  - National trends in volume-outcome relationships for extracorporeal membrane
      oxygenation.
AB  - BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) has emerged as
      a common therapy for severe cardiopulmonary dysfunction. We aimed to describe the
      relationship of institutional volume with patient outcomes and examine transfer
      status to tertiary ECMO centers. MATERIALS AND METHODS: Using the National
      Inpatient Sample, we identified adult patients who received ECMO from 2008 to
      2014. Individual hospital volume was calculated as tertiles of total
      institutional discharges for each year independently. RESULTS: Of the total
      18,684 adult patients placed on ECMO, 2548 (13.6%), 5278 (28.2%), and 10,858
      (58.1%) patients were admitted to low-, medium-, and high-volume centers,
      respectively. Unadjusted mortality at low-volume hospitals was less than that of
      medium- (43.7% versus 50.3%, P = 0.03) and high-volume hospitals (43.7% versus
      55.6%, P < 0.001). Length of stay and cost were reduced at low-volume hospitals
      compared to both medium- and large-volume institutions (all P < 0.001). In high
      volume institutions, transferred patients had greater postpropensity-matched
      mortality (58.5% versus 53.7%, P = 0.05) and cost ($190,299 versus $168,970, P =
      0.009) compared to direct admissions. On exclusion of transferred patients from
      propensity analysis, mortality remained greater in high-volume compared to low
      volume centers (50.2% versus 42.8%, P = 0.04). Predictors of mortality included
      treatment at high-volume centers, respiratory failure, and cardiogenic shock (all
      P < 0.001). CONCLUSIONS: Our findings show increased in-hospital mortality in
      high-volume institutions and in patients transferred to tertiary centers. Whether
      this phenomenon represents selection bias or transfer from another facility
      deserves further investigation and will aid with the identification of surrogate
      markers for quality of high-risk interventions.

PMID- 30278963
TI  - Do we CARE about the quality of case reports? A systematic assessment.
AB  - BACKGROUND: Clinical case reports are important sources of information on the
      identification and treatment of new or rare diseases. The CAse REport (CARE)
      Statement and Checklist represents consensus-based guidelines for clinical case
      reports. How well case reports adhere to these guidelines is unknown. MATERIAL
      AND METHODS: A systematic PubMed and OVID search was used to identify case
      reports on isolated splenic metastasis from 2007 to 2017 in English language
      journals. MeSH search terms included "(isolated splenic metastasis OR solitary
      splenic metastasis) AND case report." We retrieved 79 articles and 55 directly
      addressed the topic of interest. Each was scored dichotomously using the 13
      categories with 36 item descriptors on the CARE checklist. RESULTS: Of the 55
      case reports, none fully followed the CARE guidelines; only 56.4% met 23
      descriptors and none had more than 29 of 36 descriptors. Patient symptoms were
      not described in 40.0%, and in 47.3%, the abstract did not identify the main
      outcomes. All reports included patient's age and diagnostic methods. Most case
      reports reported the type of intervention (96.4%) and effect of the intervention
      (96.4%). None included patient-assessed outcomes or the patient's perspective.
      Only 49.1% included strengths and limitations of patient management, stating that
      the most effective treatment is unknown. CONCLUSIONS: None of the case reports on
      isolated splenic metastasis completely followed the CARE guidelines. Most reports
      did cover diagnostic workup and therapeutic interventions and gave a summary of
      the literature. Higher quality case reports would be useful in facilitating
      recognition of rare disease processes and informing clinical practice.

PMID- 30278964
TI  - Underuse of exon mutational analysis for gastrointestinal stromal tumors.
AB  - BACKGROUND: Tyrosine kinase inhibitors (TKI) have become the guideline
      recommended therapy for high-risk resected and advanced gastrointestinal stromal
      tumors (GISTs). Exon mutational analysis (EMA) is used to inform pretherapy
      response to TKI and may predict overall prognosis. Despite these benefits, EMA
      remains underused, and its impact on TKI therapy decision-making remains
      unexplored. MATERIALS AND METHODS: A retrospective cohort was established from
      104 patients receiving treatment for GISTs from 2006 to 2017. Current National
      Comprehensive Cancer Network guidelines indicate that EMA should be considered
      for all patients undergoing TKI therapy to identify genotypes that are likely, or
      unlikely, to respond to treatment. We first tracked guideline-considered EMA use
      and subsequent impact on treatment decision-making. A questionnaire was then
      administered to gastrointestinal medical oncologists to assess EMA perception.
      RESULTS: Among 104 GIST patients, 54 (52%) received TKI therapy. Of these, only
      22 (41%) received EMA. Informed by EMA, treatment decisions included 59% who
      continued with original TKI therapy, 32% who switched to an alternative TKI, and
      9% who discontinued or received no TKI. Although 92% of physicians indicated EMA
      was a valuable tool, only 62% indicated they used it "frequently" or "always" to
      inform treatment decisions. CONCLUSIONS: Less than half of patients receiving TKI
      therapy for GISTs received EMA at a comprehensive cancer center. Despite this low
      uptake, when it was performed, EMA guided alternative treatment decision in 41%
      of patients. Physician survey responses indicated that interventions targeting
      physician education and an electronic medical record reminder may improve EMA
      uptake.

PMID- 30278965
TI  - Extended neuromuscular blockade in acute respiratory distress syndrome does not
      increase mortality.
AB  - BACKGROUND: Neuromuscular blockade (NMB) is often utilized in the treatment of
      acute respiratory distress syndrome (ARDS). Its use for a period of 48 h has been
      shown to improve mortality in randomized control trials. We aimed to characterize
      outcomes associated with a prolonged NMB. We hypothesized that the duration of
      NMB would not be associated with increased mortality. MATERIALS AND METHODS: This
      was a retrospective review from June 2014 to October 2016 of patients admitted to
      the surgical intensive care unit and receiving cisatracurium for ARDS. Patients
      paralyzed for <= 48 h (SHORT) were compared to those paralyzed for longer
      durations (LONG). Primary outcome was mortality. Parametric and nonparametric
      tests were utilized for the purposes of the comparison. A multivariate logistic
      regression model was utilized to adjust for differences. RESULTS: Of 73 patients
      meeting inclusion criteria, 32 (44%) were SHORT and 41 (56%) LONG. Compared to
      the LONG cohort, those in SHORT were older (60 versus 52 years, P = 0.04) but
      were comparable with respect to sex, acute physiology and chronic health
      evaluation IV scores, presence of concurrent pneumonia, and the use of
      vasopressors. SHORT patients were less likely to require rescue therapy with
      inhaled nitric oxide (28% versus 66%, P < 0.01). Overall mortality was 60%. There
      was no difference in the adjusted odds for mortality (adjusted odds ratio: 0.57,
      P = 0.33). Secondary outcomes including deep venous thrombosis and pneumonia did
      not differ between the two groups. CONCLUSIONS: Extended NMB for ARDS was not
      associated with increased mortality. Discontinuation of this modality should not
      be based solely on the duration of therapy.

PMID- 30278966
TI  - Cost-effectiveness of surgeon performed intraoperative specimen ink in breast
      conservation surgery.
AB  - BACKGROUND: Re-excision rates after breast conservation surgery are reported to
      be 20%-40%. Inaccuracies with specimen orientation may affect margin assessment.
      This study examined whether the addition of surgeon performed intraoperative
      inking of the lumpectomy specimen after adoption of margin guidelines would be
      cost-effective. METHODS: A retrospective review of a prospective surgical
      database was performed from 2009 to 2017. Patients with initial lumpectomy and a
      preoperative diagnosis of invasive breast carcinoma or ductal carcinoma in situ
      (DCIS) were included. Re-excision rates and the surgical costs per 100 initial
      lumpectomies were compared across three periods: before margin guideline
      publication, after guideline adoption, and after the addition of intraoperative
      surgeon performed specimen inking. RESULTS: Four hundred initial lumpectomies
      were evaluated. Overall re-excision rate was 21% (n = 84). There was a
      nonsignificant reduction in re-excision rates after margin guidelines from 24% (n
      = 36) to 20% (n = 23) and to 19% (n = 25) after addition of intraoperative
      specimen ink. Re-excision rates were significantly lower for invasive cancer than
      for DCIS across three periods (20%, 15%, and 12% versus 37%, 33%, and 31%) (odds
      ratio 3.31, P = 0.007). The estimated cost of re-excision per 100 initial
      lumpectomies decreased after guidelines by 25% ($128,270) for invasive breast
      cancer and by 11% ($102,616) for DCIS. The addition of intraoperative specimen
      inking after margin guideline adoption resulted in further 17% cost savings
      ($66,692) for invasive breast cancer and 5% ($41,308) for DCIS. CONCLUSIONS:
      Surgeon performed intraoperative inking of the lumpectomy specimen after adoption
      of margin guidelines is a cost-effective technique in breast conservation
      surgery.

PMID- 30278967
TI  - MC1R gene polymorphisms are associated with dysfunctional immune responses and
      wound infection after burn injury.
AB  - BACKGROUND: Systemic inflammatory response syndrome (SIRS) is associated with
      organ failure and infectious complications after major burn injury. Recent
      evidence has linked melanocortin signaling to anti-inflammatory and wound-repair
      functions, with mutations in the melanocortin 1 receptor (MC1R) gene leading to
      increased inflammatory responses. Our group has previously demonstrated that MC1R
      gene polymorphisms are associated with postburn hypertrophic scarring. Thus, we
      hypothesized that MC1R single nucleotide polymorphisms (SNPs) would be associated
      with increased burn-induced SIRS and increased infectious complications. METHODS:
      We performed a retrospective cohort study of adults (>18 y of age) admitted to
      our burn center with >20% total body surface area (TBSA) partial/full thickness
      burns between 2006 and 2013. We screened for five MC1R SNPs (V60L, V92M, R151C,
      R163Q, T314T) by polymerase chain reaction from genomic DNA isolated from blood
      samples. We performed a detailed review of each patient chart to identify age,
      sex, race, ethnicity, %TBSA burned, burn wound infections (BWIs), and 72-hr
      intravenous fluid volume, the latter a surrogate for a dysfunctional inflammatory
      response to injury. Association testing was based on multivariable regression.
      RESULTS: Of 106 subjects enrolled, 82 had complete data for analysis. Of these,
      64 (78%) were male, with a median age of 39 and median burn size of 30% TBSA. A
      total of 36 (44%) subjects developed BWIs. The median total administered IV
      crystalloid in first 72h was 24.6 L. In multivariate analysis, the R151C variant
      allele was a significant independent risk factor for BWI (adjusted prevalence
      ratio 2.03; 95% CI: 1.21-3.39; P = 0.007), and the V60L variant allele was
      independently associated with increased resuscitation fluid volume (P = 0.021).
      CONCLUSIONS: This is the first study to demonstrate a significant association
      between genetic polymorphisms and a nonfatal burn-induced SIRS complication. Our
      findings suggest that MC1R polymorphisms contribute to dysfunctional responses to
      burn injury that may predict infectious and inflammatory complications.

PMID- 30278968
TI  - Do surgeons and patients/parents value shared decision-making in pediatric
      surgery? A systematic review.
AB  - BACKGROUND: Shared decision-making (SDM) is touted as the preferred approach to
      clinical counseling. However, few data exist regarding whether patients prefer
      SDM over surgeon-guided discussions for complex surgical decision-making. Even
      fewer data exist regarding surgeon preferences. Such issues may be especially
      pronounced in pediatric surgery given the complex decision-making triad between
      patients/parents and surgeons. The objective of this systematic review was to
      evaluate patient/parent and surgeon attitudes toward SDM in pediatric surgery.
      METHODS: A systematic review of English language articles in Medline, EMBASE, and
      Cochrane databases was performed. Inclusion and exclusion criteria were
      predefined. Text screening and data abstraction were performed by two
      investigators. RESULTS: Seven thousand five hundred eighty-four articles were
      screened. Title/abstract review excluded 7544 articles, and full-text review
      excluded four articles. Thirty-six articles were identified as addressing
      patient/parent or surgeon preferences toward SDM in pediatric surgery.
      Subspecialties included Otolaryngology (33%), General Surgery (30%), Plastics
      (14%), Cardiac (11%), Urology (8%), Neurosurgery (6%), Orthopedics (6%), and
      Gynecology (3%). Most studies (94%) evaluated elective/nonurgent procedures. The
      majority (97%) concentrated on patient/parent preferences, whereas only 22%
      addressed surgeon preferences. Eleven percent of studies found that surgeons
      favored SDM, and 73% demonstrated that patients/parents favored SDM. CONCLUSIONS:
      Despite recommendations that SDM is the preferred approach to clinical
      counseling, our systematic literature review shows that few studies evaluate
      patient/parent and surgeon attitudes toward SDM in pediatric surgery. Of these
      studies, very few focus on complex, urgent/emergent decision-making. Further
      research is needed to understand whether patients/parents, as well as surgeons,
      may prefer a more surgeon-guided approach to decision-making, especially when
      surgery is complex or taking place in urgent/emergent settings.

PMID- 30278970
TI  - Failure to rescue and disparities in emergency general surgery.
AB  - BACKGROUND: Racial and socioeconomic disparities are well documented in emergency
      general surgery (EGS) and have been highlighted as a national priority for
      surgical research. The aim of this study was to identify whether disparities in
      the EGS setting are more likely to be caused by major adverse events (MAEs)
      (e.g., venous thromboembolism) or failure to respond appropriately to such
      events. METHODS: A retrospective cohort study was undertaken using administrative
      data. EGS cases were defined using International Classification of Diseases,
      Ninth Revision, Clinical Modification diagnostic codes recommended by the
      American Association for the Surgery of Trauma. The data source was the National
      Inpatient Sample 2012-2013, which captured a 20%-stratified sample of discharges
      from all hospitals participating in the Healthcare Cost and Utilization Project.
      The outcomes were MAEs, in-hospital mortality, and failure to rescue (FTR).
      RESULTS: There were 1,345,199 individual patient records available within the
      National Inpatient Sample. There were 201,574 admissions (15.0%) complicated by
      an MAE, and 12,006 of these (6.0%) resulted in death. The FTR rate was therefore
      6.0%. Uninsured patients had significantly higher odds of MAEs (adjusted odds
      ratio, 1.16; 95% confidence interval, 1.13-1.19), mortality (1.28, 1.16-1.41),
      and FTR (1.20, 1.06-1.36) than those with private insurance. Although black
      patients had significantly higher odds of MAEs (adjusted odds ratio, 1.14; 95%
      confidence interval, 1.13-1.16), they had lower mortality (0.95, 0.90-0.99) and
      FTR (0.86, 0.80-0.91) than white patients. CONCLUSIONS: Uninsured EGS patients
      are at increased risk of MAEs but also the failure of health care providers to
      respond effectively when such events occur. This suggests that MAEs and FTR are
      both potential targets for mitigating socioeconomic disparities in the setting of
      EGS.

PMID- 30278969
TI  - Microfluidics contrasted to thrombelastography: perplexities in defining
      hypercoagulability.
AB  - BACKGROUND: Elevated clot strength (maximum amplitude [MA]) measured by
      thrombelastography (TEG) is associated with thrombotic complications. However, it
      remains unclear how MA translates to thrombotic risks, as this measurement is
      independent of time, blood flow, and clot degradation. We hypothesize that under
      flow conditions, increased clot strength correlates to time-dependent
      measurements of coagulation and resistance to fibrinolysis. MATERIALS AND
      METHODS: Surgical patients at high risk of thrombotic complications were analyzed
      with TEG and total thrombus-formation analysis system (T-TAS). TEG
      hypercoagulability was defined as an r <10.2 min, angle >59, MA >66 or LY30 <0.2%
      (based off of healthy control data, n = 141). The T-TAS AR and PL chips were used
      to measure clotting at arterial shear rates. T-TAS measurements include occlusion
      start time, occlusion time (OT), occlusion speed (OSp), and total clot generation
      (area under the curve). These measurements were correlated to TEG indices (R
      time, angle, MA, and LY30). Both T-TAS and TEG assays were challenged with tissue
      plasminogen activator (t-PA) to assess clot resistance to fibrinolysis. RESULTS:
      Thirty subjects were analyzed, including five controls. TEG-defined
      hypercoagulability by MA was detected in 52% of the inflammatory bowel
      disease/cancer patients; 0% was detected in the controls. There were no TEG
      measurements that significantly correlated with T-TAS AR and PL chip. However, in
      the presence of t-PA, T-TAS AR determined OSp to have an inverse relationship
      with TEG angle (-0.477, P = 0.012) and LY30 (-0.449, P = 0.019), and a positive
      correlation with R time (0.441 P = 0.021). In hypercoagulability determined by
      TEG MA, T-TAS PL had a significantly reduced OT (4:07 versus 6:27 min, P =
      0.043). In hypercoagulability defined by TEG LY30, T-TAS PL had discordant
      findings, with a significantly prolonged OT (6:36 versus 4:30 min, P = 0.044) and
      a slower OSp (10.5 versus 19.0 kPa/min, P = 0.030). CONCLUSIONS: Microfluidic
      coagulation assessment with T-TAS has an overall poor correlation with most TEG
      measurements in a predominantly hypercoagulable patient population, except in the
      presence of t-PA. The one anticipated finding was an elevated MA having a shorter
      time to platelet-mediated microfluidic occlusion, supporting the role of
      platelets and hypercoagulability. However, hypercoagulability defined by LY30 had
      opposing results in which a low LY30 was associated with a longer PL time to
      occlusion and slower OSp. These discordant findings warrant ongoing investigation
      into the relationship between clot strength and fibrinolysis under different flow
      conditions.

PMID- 30278971
TI  - Frequency and timing of short-term complications following abdominoperineal
      resection.
AB  - BACKGROUND: Abdominoperineal resection (APR) is primarily used for rectal cancer
      and is associated with a high rate of complications. Though the majority of APRs
      are performed as open procedures, laparoscopic APRs have become more popular. The
      differences in short-term complications between open and laparoscopic APR are
      poorly characterized. METHODS: We conducted a retrospective cohort study using
      the American College of Surgeons National Surgical Quality Improvement Program
      database to determine the frequency and timing of onset of 30-d postoperative
      complications after APR and identify differences between open and laparoscopic
      APR. RESULTS: A total of 7681 patients undergoing laparoscopic or open APR
      between 2011 and 2015 were identified. The total complication rate for APR was
      high (45.4%). APRs were commonly complicated by blood transfusion (20.1%),
      surgical site infection (19.3%), and readmission (12.3%). Laparoscopic APR was
      associated with a 14% lower total complication rate compared to open APR (36.0%
      versus 50.1%, P < 0.001). This was primarily driven by a decreased rate of
      transfusion (10.7% versus 24.9%, P < 0.001) and surgical site infection (15.5%
      versus 21.2%, P < 0.001). Laparoscopic APR had shorter length of stay and
      decreased reoperation rate but similar rates of readmission and death.
      Cardiopulmonary complications occurred earlier in the postoperative period after
      APR, whereas infectious complications occurred later. CONCLUSIONS: Short-term
      complications following APR are common and occur more frequently in patients who
      undergo open APR. This, along with factors such as risk of positive pathologic
      margins, surgeon skill set, and patient characteristics, should contribute to the
      decision-making process when planning rectal cancer surgery.

PMID- 30278972
TI  - Intraoperative fluid restriction in hyperthermic intraperitoneal chemotherapy.
AB  - BACKGROUND: Multiple studies highlight the importance of liberal fluid
      administration in cytoreductive surgery (CRS) with hyperthermic intraperitoneal
      chemotherapy (HIPEC). Over-resuscitation can delay recovery and wound healing. We
      report an intraoperative protocol that restricts fluid administration and
      minimizes morbidity. MATERIALS AND METHODS: Retrospective analysis of 35 patients
      that underwent CRS-HIPEC for curative intent under fluid restriction protocol
      from June 2015 to July 2017 was performed. Protocol consists of continuous
      infusion of vasopressin 0.02 units/h and maintaining urine output at 0.5 mL/kg/h
      via crystalloid and colloid. Endpoint was Clavien-Dindo >=3 events within 30 d of
      CRS-HIPEC. RESULTS: Median age was 56 y; 71% were female. Malignancies treated:
      appendix (49%), colon (31%), and other (20%). Median peritoneal cancer index was
      15, complete cytoreduction was achieved in 91% of patients. Median time for
      return of bowel function was 5 d, median length of hospital stay was 7 d. There
      were 28 bowel anastomoses. Median intraoperative crystalloid, colloid, and packed
      red blood cells were (1900, 1500, and 700 mL), respectively. Clavien-Dindo grade
      3-4 events occurred in five patients. There were no deaths 30 d after surgery.
      CONCLUSIONS: A fluid restriction protocol appears to be safe and feasible in the
      setting of CRS-HIPEC for curative intent.

PMID- 30278973
TI  - Inhibition of autophagy after perforator flap surgery increases flap survival and
      angiogenesis.
AB  - BACKGROUND: The survival ratio of multiterritory perforator flap is variable.
      Therefore, surviving mechanisms are increasingly explored to identify novel
      therapeutics. The condition of the choke zone is essential for perforator flap
      survival. In this study, we investigated autophagy in the choke zone after flap
      surgery. MATERIALS AND METHODS: The flap model involved a perforator flap with
      three territories that was located on the right dorsal side of a rat. A total of
      36 rats were divided into six groups, including the control, 0 d postoperative
      (PO), 1, 3, 5, and 7 d PO groups. In addition, 72 rats were divided into three
      groups, including a control group, a 3-methyladenine (3-MA) group, and a
      rapamycin group. Skin tissue of rats was used for measuring autophagy proteins,
      vascular endothelial growth factor (VEGF) expression, and histological
      examination. On day 7 after surgery, the survival ratio of each flap was
      determined. RESULTS: The expression of autophagy and VEGF in the second choke
      zone (choke II) was increased after flap surgery. Among the three groups, the
      survival ratio of flaps in the 3-MA group was the highest. Furthermore, the
      angiogenesis level in the 3-MA group in choke II was the highest among the three
      groups. CONCLUSIONS: Autophagy was initiated by surgery in choke II, and VEGF
      expression in choke II was increased after flap surgery. Inhibiting autophagy
      after perforator flap surgery is beneficial for flap survival and for promoting
      angiogenesis in choke II.

PMID- 30278974
TI  - Contralateral medial pectoral nerve transfer with free gracilis muscle transfer
      in old brachial plexus palsy.
AB  - BACKGROUND: There is a very small chance of success for nerve reconstruction in
      patients with old total brachial plexus palsy who visit after 2 y or suffer from
      flail upper extremity after the failure of previous operations. MATERIALS AND
      METHODS: For these individuals, the surgeon has to find a recipient motor nerve
      to perform free gracilis muscle transplantation. In this study, contralateral
      medial pectoral nerve from the intact side was transferred to the damaged side as
      a recipient nerve. Then, in the second operation, approximately 15 mo later, the
      free gracilis muscle transfer was performed. The gracilis muscle was removed and
      transferred to provide elbow and finger flexion. RESULTS: In a retrospective
      study (over 10 y), we reviewed 68 patients for whom this method had been
      performed. After 1 y, the results were investigated using the Medical Research
      Council grading system. Five patients did not participate in the study, and the
      muscle underwent necrosis in two patients. M3 and M4 muscle power was regained in
      26 (42.6%) and 21 (34.4%) patients, respectively. CONCLUSIONS: Contralateral
      pectoral nerve transfer followed by free muscle transplantation can be a good
      option for patients with old total brachial plexus palsy.

PMID- 30278975
TI  - Long-term consequences of abdominal aortic and junctional tourniquet for
      hemorrhage control.
AB  - BACKGROUND: Specialized tourniquets have been deployed to the battlefield for the
      control of junctional/pelvic hemorrhage despite limited knowledge concerning
      their safety and duration of use. This study investigated long-term effects of
      abdominal application of the abdominal aortic and junctional tourniquet (AAJT) in
      a swine survival model. METHODS: Anesthetized spontaneously air-breathing swine
      were subjected to bilateral femoral artery injuries and subsequent 40%
      hemorrhage. Further hemorrhage was controlled by applying the AAJT on the lower
      abdomen for 0 h (n = 2, controls), 1 h (n = 6), 1.5 h (n = 6), or 2 h (n = 3).
      Before tourniquet release, arterial injuries were repaired, and mechanical
      ventilation and rapid crystalloid fluid were provided for at least 5 min.
      Additional fluid and 500 mL autologous blood were transfused after restoring
      blood flow. Animals were recovered and their mobility and health monitored up to
      2 wk. RESULTS: AAJT application occluded the infrarenal abdominal aorta and
      stopped bilateral groin hemorrhage with rapid reversal of hemorrhagic shock and
      improved cranial blood pressure. All animals including controls recovered
      overnight but regaining hind leg function varied among AAJT-treated groups. In
      contrast to 1 h AAJT-treated swine that recovered full mobility in 1 wk, 2 h
      animals developed persistent hind leg paraplegia concurrent with urinary
      retention and ischemic necrosis of lumber muscles and had to be euthanized 3 d
      after surgery. Half of the 1.5-h group also had to be euthanized early due to
      paraplegia, whereas the other half recovered motor function within 2 wk.
      CONCLUSIONS: The results of this animal study indicated that ischemic reperfusion
      injuries associated with abdominal application of the AAJT were time-dependent.
      To avoid permanent injuries, AAJT application on the abdomen to control a groin
      hemorrhage could not be longer than 1 h. This was consistent with recent
      instructions for application of this tourniquet on the abdomen in patients.

PMID- 30278977
TI  - Improving laboratory studies of human eating behaviour: Energy balance and real
      world considerations.

PMID- 30278978
TI  - Commentary: Methodological and reporting practices for laboratory studies
      assessing food intake using fixed and ad libitum test meals.

PMID- 30278979
TI  - Studying human eating behaviour in the laboratory: Theoretical considerations and
      practical suggestions.
AB  - Robinson and colleagues (2018) make important first steps in highlighting the
      shortcomings of laboratory studies of human eating behaviour, and providing some
      general suggestions to increase methodological and reporting quality. In this
      commentary, we present additional important theoretical considerations and
      practical suggestions. First, we discuss the role of situational cues in eating
      behaviour and highlight the implications for designing ecologically valid
      laboratory experiments. Next, we discuss food intake in laboratory settings in
      the context of the distinction between implicit and explicit measures used widely
      in social psychology, and provide practical recommendations to keep intake a
      relatively implicit measure. Finally, we recognise that designing optimal
      experiments requires significant resources so we present a practical procedure to
      recruit the smallest informative sample via Bayesian sequential hypothesis
      testing.

PMID- 30278980
TI  - Shielding disk position in intra-operative electron radiotherapy (IOERT): A Monte
      Carlo study.
AB  - PURPOSE: In IOERT breast treatments, a shielding disk is frequently used to
      protect the underlying healthy structures. The disk is usually composed of two
      materials, a low-Z material intended to be oriented towards the beam and a high-Z
      material. As tissues are repositioned around the shield before treatment, the
      disk is no longer visible and its correct alignment with respect to the beam is
      guaranteed. This paper studies the dosimetric characteristics of four possible
      clinical positioning scenarios of the shielding disk. A new alignment method for
      the shielding disk in the beam is introduced. Finally, it suggests a new design
      for the shielding disk. METHODS: As the first step, the IOERT machine "Mobetron
      1000" was modeled by using Monte Carlo simulation, tuning the MC model until an
      excellent match with the measured PDDs and profiles was achieved. Four possible
      shielding disk positioning scenarios were considered, determining the dosimetric
      impact. Furthermore, in our center, to prevent beam misalignment, we have
      developed a shielding disk equipped with guiding rods. Having ascertained a
      correct alignment between the disk and the beam, we can propose a new internal
      design of the shielding disk that can improve the dose distribution with a better
      coverage of the treated area. RESULTS: All MC simulations were performed with a
      12 MeV beam, the maximum energy of Mobetron 1000 and a 5.5 cm diameter flat tip
      applicator, this applicator being the most clinically used. The simulations were
      compared with measurements performed in a water phantom and showed good results
      within 2.2% of root mean square difference (RMSD). The misplacement positions of
      the shielding disk have dosimetric impacts in the treatment volume and a small
      translation could have a significant influence on healthy tissues. The D-scenario
      is the worst which could happens when the shielding disk is flipped upside down,
      giving up to 144% dose instead of 90% at the surface of the Pb/Al shielding disk.
      A new shielding design used, together with our alignment tool, is able to give a
      more homogeneous dose in the target area. CONCLUSIONS: The accuracy of shielding
      disk position can still be problematic in IOERT dosimetry. Any method that can
      ascertain the good alignment between the shielding disk and the beam is
      beneficial for the dose distribution and is a prerequisite for an optimized
      shield internal design that could improve the coverage of the treated area and
      the protection of healthy tissues.

PMID- 30278982
TI  - Monte Carlo dose verification of VMAT treatment plans using Elekta Agility 160
      leaf MLC.
AB  - In this study, we verified volumetric modulated arc therapy (VMAT) plans in an
      Elekta Synergy system with an integrated Agility 160-leaf multileaf collimator
      (MLC) by comparing them with Monte Carlo (MC)-calculated dose distributions using
      the AAPM TG-119 structure sets. The head configuration of the linear accelerator
      with the integrated MLC was simulated with the EGSnrc/BEAMnrc code. Firstly, the
      dosimetric properties of the MLC were evaluated with the MC technique and film
      measurements. Next, VMAT plans were created with the Pinnacle3 treatment planning
      system (TPS) for four regions in the AAPM TG-119 structures. They were then
      verified by comparing them with MC-calculated dose distributions using dose
      volume histograms (DVHs) and three-dimensional (3D) gamma analysis. The MC
      simulations for the Agility MLC dosimetric properties were in acceptable
      agreement with measurements. TPS-VMAT plans using TG-119 structure sets agreed
      with MC dose distributions within 2% in the comparison of D95 in planning target
      volumes (PTVs) evaluated from DVHs. In contrast, higher dose regions such as D20,
      D10, and D5 in PTVs for TPS tended to be smaller than MC values. This tendency
      was particularly noticeable for mock head and neck with complicated structures.
      In 3D gamma analysis, the passing rates with 3%/3mm criteria in PTVs were >=99%,
      except for mock head and neck (89.5%). All passing rates for organs at risk
      (OARs) were in acceptable agreement of >96%. It is useful to verify dose
      distributions of PTVs and OARs in TPS-VMAT plans by using MC dose calculations
      and 3D gamma analysis.

PMID- 30278981
TI  - Physical parameter optimization scheme for radiobiological studies of charged
      particle therapy.
AB  - We have developed an easy-to-implement method to optimize the spatial
      distribution of a desired physical quantity for charged particle therapy. The
      basic methodology requires finding the optimal solutions for the weights of the
      constituent particle beams that together form the desired spatial distribution of
      the specified physical quantity, e.g., dose or dose-averaged linear energy
      transfer (LETd), within the target region. We selected proton, 4He ion, and 12C
      ion beams to demonstrate the feasibility and flexibility of our method. The
      pristine dose Bragg curves in water for all ion beams and the LETd for proton
      beams were generated from Geant4 Monte Carlo simulations. The optimization
      algorithms were implemented using the Python programming language. High-accuracy
      optimization results of the spatial distribution of the desired physical quantity
      were then obtained for different cases. The relative difference between the real
      value and the expected value of a given quantity was approximately within +/-1.0%
      in the whole target region. The optimization examples include a flat dose spread
      out Bragg peak (SOBP) for the three selected ions, an upslope dose SOBP for
      protons, and a downslope dose SOBP for protons. The relative difference was
      approximately within +/-2.0% for the case with a flat LETd (target value = 4
      keV/um) distribution for protons. These one-dimensional optimization algorithms
      can be extended to two or three dimensions if the corresponding physical data are
      available. In addition, this physical quantity optimization strategy can be
      conveniently extended to encompass biological dose optimization if appropriate
      biophysical models are invoked.

PMID- 30278983
TI  - High resolution hard X-ray 3D mapping of a Macaca fascicularis eye: A feasibility
      study without contrast agents.
AB  - Several complementary methods able to visualize the internal structures of eyes
      are used in the clinical practice in the diagnosis of pathologies affecting a
      specific zone of the eye. Despite the significant technological progress, the
      visualization of the entire eyeball at micrometric resolution is yet an unsolved
      task both in clinical diagnostics and in laboratory research. With this respect,
      high resolution 3D images of the eyeball would be extremely useful, in the study
      of various pathologies of the retina, the lens, and of the optic nerve. In this
      work we combined the state-of-the-art of micro computed tomography technology
      with phase-contrast imaging, a recent highly sensitive technique well adapted to
      investigate soft tissues without the use of contrast agents; we applied the
      technique in the post-mortem analysis of monkey eyes, which share several
      similitudes with the human organ. We reported here vascular, nervous and
      anatomical details of monkey eyes imaged with a 3.1 * 3.1 * 3.1 um3 voxel size as
      well as the first 3D visualisation of the entire globe of Macaca's fascicularis
      eye. Results have also been compared with, and validated by, histological
      analysis.

PMID- 30278984
TI  - Adherence to APSA activity restriction guidelines and 60-day clinical outcomes
      for pediatric blunt liver and splenic injuries (BLSI).
AB  - BACKGROUND: After NOM for BLSI, APSA guidelines recommend activity restriction
      for grade of injury +2 in weeks. This study evaluates activity restriction
      adherence and 60 day outcomes. METHODS: Non-parametric tests and logistic
      regression were utilized to assess difference between adherent and non-adherent
      patients from a 3-year prospective study of NOM for BLSI (<=18 years). RESULTS:
      Of 1007 children with BLSI, 366 patients (44.1%) met the inclusion criteria of a
      completed 60 day follow-up; 170 (46.4%) had liver injury, 159 (43.4%) had spleen
      injury and 37 (10.1%) had both. Adherence to recommended activity restriction was
      claimed by 279 (76.3%) patients; 49 (13.4%) reported non-adherence and 38 (10.4%)
      patients had unknown adherence. For 279 patients who adhered to activity
      restrictions, unplanned return to the emergency department (ED) was noted for 35
      (12.5%) with 16 (5.7%) readmitted; 202 (72.4%) returned to normal activity by 60
      days. No patient bled after discharge. There was no statistical difference
      between adherent patients (n = 279) and non-adherent (n = 49) for return to ED
      (chi2 = 0.8 [p < 0.4]) or readmission (chi2 = 3.0 [p < 0.09]); for 216 high
      injury grade patients, there was no difference between adherent (n = 164) and non
      adherent (n = 30) patients for return to ED (chi2 = 0.6 [p < 0.4]) or readmission
      (chi2 = 1.7 [p < 0.2]). CONCLUSION: For children with BLSI, there was no
      difference in frequencies of bleeding or ED re-evaluation between patients
      adherent or non-adherent to the APSA activity restriction guideline. LEVEL OF
      EVIDENCE: Level II, Prognosis.

PMID- 30278985
TI  - Prognostic utility of noninvasive estimates of pulmonary vascular compliance in
      neonates with congenital diaphragmatic hernia.
AB  - AIM: To evaluate echocardiographic indices of pulmonary vascular resistance and
      right ventricular (RV) function in predicting death or ECMO in congenital
      diaphragmatic hernia (CDH). METHODS: In this single center study, early (<48 h)
      echocardiograms of neonates with CDH (n = 47) were reviewed by a single reader
      for the ratio of tricuspid regurgitant velocity to velocity time integral at the
      pulmonary valve (TRV/VTIpv), TRV2/VTIpv, RV fractional area change (FAC) and
      tricuspid annular plane systolic excursion (TAPSE). Receiver operating
      characteristic curves were generated for each parameter to obtain optimal cutoff
      values. RESULTS: Infants who died or received ECMO (n = 30) had significantly
      higher TRV/VTIpv and TRV2/VTIpv, and lower VTIpv, RV FAC and TAPSE, compared to
      the 17 survivors without ECMO. For TRV2/VTIpv and TRV/VTI at cutoffs of 1.3 and
      0.38 respectively, the sensitivities were 92.3 (95% CI 75-99.1%) and 96 (95% CI
      80.4-99.9%), specificities were 78.6 (49.2-95.4%) and 71.4 (42-91.6%), positive
      predictive values were 89 (75-95.6%) and 86.2 (73.2-93.5%) and negative
      predictive values were 84.6 (58.5-95.5%) and 90.9 (58.7-98.6%). CONCLUSION: Early
      echocardiographic evidence of pulmonary hypertension and RV dysfunction predicts
      outcome in CDH. Further studies utilizing these indices to guide therapeutic
      decision-making are warranted. LEVEL OF EVIDENCE: Level 1 for diagnostic study.

PMID- 30278986
TI  - Margin status and long-term prognosis of primary pancreatic neuroendocrine tumor
      after curative resection: Results from the US Neuroendocrine Tumor Study Group.
AB  - BACKGROUND: The impact of margin status on resection of primary pancreatic
      neuroendocrine tumors has been poorly defined. The objectives of the present
      study were to determine the impact of margin status on long-term survival of
      patients with pancreatic neuroendocrine tumors after curative resection and
      evaluate the impact of reresection to obtain a microscopically negative margin.
      METHODS: Patients who underwent curative-intent resection for pancreatic
      neuroendocrine tumors between 2000 and 2016 were identified at 8 hepatobiliary
      centers. Overall and recurrence-free survival were analyzed relative to surgical
      margin status using univariable and multivariable analyses. RESULTS: Among 1,020
      patients, 866 (84.9%) had an R0 (>1 mm margin) resection, whereas 154 (15.1%) had
      an R1 (<=1 mm margin) resection. R1 resection was associated with a worse
      recurrence-free survival (10-year recurrence-free survival, R1 47.3% vs R0 62.8%,
      hazard ratio 1.8, 95% confidence interval 1.2-2.7, P = .002); residual tumor at
      either the transection margin (R1t) or the mobilization margin (R1m) was
      associated with increased recurrence versus R0 (R1t versus R0: hazard ratio 1.8,
      95% confidence interval 1.0-3.0, P = .033; R1m versus R0: hazard ratio 1.3, 95%
      confidence interval 1.0-1.7, P = .060). In contrast, margin status was not
      associated with overall survival (10-year overall survival, R1 71.1% vs R0 71.8%,
      P = .392). Intraoperatively, 539 (53.6%) patients had frozen section evaluation
      of the surgical margin; 49 (9.1%) patients had a positive margin on frozen
      section analysis; 38 of the 49 patients (77.6%) had reresection, and a final R0
      (secondary R0) margin was achieved in 30 patients (78.9%). Extending resection to
      achieve an R0 status remained associated with worse overall survival (hazard
      ratio 3.1, 95% confidence interval 1.6-6.2, P = .001) and recurrence-free
      survival (hazard ratio 2.6, 95% confidence interval 1.4-5.0, P = .004) compared
      with primary R0 resection. On multivariable analyses, tumor-specific factors,
      such as cellular differentiation, perineural invasion, Ki-67 index, and major
      vascular invasion, rather than surgical margin, were associated with long-term
      outcomes. CONCLUSION: Margin status was not associated with long-term survival.
      The reresection of an initially positive surgical margin to achieve a negative
      margin did not improve the outcome of patients with pancreatic neuroendocrine
      tumors. Parenchymal-sparing pancreatic procedures for pancreatic neuroendocrine
      tumors may be appropriate when feasible.

PMID- 30278987
TI  - Non-Viral Delivery To Enable Genome Editing.
AB  - Genome-editing technologies such as zinc-finger nucleases (ZFNs), transcription
      activator-like effector nucleases (TALENS), and the clustered regularly
      interspaced short palindromic repeat (CRISPR)-associated protein system have
      revolutionized biological research. Each biotechnology consists of a DNA-binding
      protein that can be programmed to recognize and initiate double-strand breaks
      (DSBs) for site-specific gene modification. These technologies have the potential
      to be harnessed to cure diseases caused by aberrant gene expression. To be
      successful therapeutically, their functionality depends on their safe and
      efficient delivery into the cell nucleus. This review discusses the challenges in
      the delivery of genome-editing tools, and highlights recent innovations in non
      viral delivery that have potential to overcome these limitations and advance the
      translation of genome editing towards patient care.

PMID- 30278988
TI  - Redox cell signaling and hepatic progenitor cells.
AB  - Hepatic diseases are widespread in the world and organ transplantation is
      currently the only treatment for liver failure. New cell-based approaches have
      been considered, since stem cells may represent a possible source to treat liver
      diseases. Acute and chronic liver diseases are characterized by high production
      of reactive oxygen and nitrogen species, with consequent oxidative modifications
      of cellular macromolecules and alteration of signaling pathways, metabolism and
      cell cycle. Although considered harmful molecules, reactive species are involved
      in cell growth and differentiation processes, modulating the activity of
      transcription factors, which take part in stemness/proliferation. It is
      conceivable that redox balance may regulate the development of hepatic progenitor
      cells, function and survival in synchrony with metabolism during chronic liver
      diseases. This review aims to summarize diverse redox-sensitive signaling
      pathways involved in stem cell fate, highlighting the important role of hepatic
      progenitor cells as a possible source to treat end-stage liver disease for organ
      regeneration.

PMID- 30278989
TI  - Reply to: "Call for an ezetimibe effectivess test".

PMID- 30278990
TI  - Hypercholesterolemia impairs megakaryopoiesis and platelet production in
      scavenger receptor BI knockout mice.
AB  - BACKGROUND AND AIMS: Thrombocytopenia in scavenger receptor BI (SR-BI) knockout
      mice is suggested to result from augmented platelet clearance induced by elevated
      intracellular unesterified cholesterol (UC) levels. We hypothesize that SR-BI
      deficiency may also influence platelet production at the level of its precursor
      cell in the bone marrow, the megakaryocyte. METHODS: In this study, we compared
      megakaryopoiesis and platelet production in SR-BI knockout and wild-type mice.
      RESULTS: In line with our hypothesis, megakaryocytes from SR-BI knockout mice
      exhibited UC accumulation while no accumulation of UC was detectable in wild-type
      megakaryocytes. Bone marrow expression of transcription factors involved in
      megakaryocyte maturation was induced, but megakaryocyte counts were unchanged in
      bone marrow of SR-BI knockout mice. Interestingly, we did find a striking 62%
      decrease (p < 0.01) in proplatelet production by SR-BI knockout megakaryocytes.
      SR-BI knockout mice displayed an impaired increase in circulating platelet
      concentrations and bone marrow megakaryocyte numbers upon thrombopoietin
      challenge. Importantly, megakaryocytes from normolipidemic bone marrow-specific
      SR-BI knockout mice exhibited a normal ability to produce proplatelets. Moreover,
      bone marrow-specific deletion of SR-BI did not impair the thrombopoietin response
      or induce thrombocytopenia, confirming that absence of megakaryocyte SR-BI does
      not underlie the thrombocytopenic phenotype in total body SR-BI knockout mice.
      CONCLUSIONS: In conclusion, the elevation of plasma unesterified cholesterol
      levels impairs megakaryopoiesis and platelet production in SR-BI knockout mice.
      Our findings suggest that, in addition to an increased platelet clearance, a
      decrease in platelet production may also, in part, explain the thrombocytopenic
      phenotype associated with SR-BI deficiency in mice.

PMID- 30278991
TI  - Rebalancing health systems toward community-based care: The role of subsectoral
      politics.
AB  - There has been increased policy discourse urging a "rebalancing" of health
      systems from institutionally-based to community-based approaches. This paper
      offers an analysis of the subsectoral dynamics that condition opportunities to
      strengthen community-based care relative to acute care. We report on the results
      of a policy study in Ontario, Canada that explored factors impacting on the
      capacity to expand community-based care. In so doing, we highlight the challenges
      associated with the community subsector's ability to develop 'critical' status
      and challenge the dominance of the acute subsector. We conclude that attempts to
      rebalance health systems toward community-based care should begin by
      understanding that health care is not a monolithic policy sector, but rather a
      collection of proximate policy sub-sectors, inclusive of community care, acute
      care, and institutional care, each with their own internal characteristics and
      dynamics that impact sectoral directions.

PMID- 30278992
TI  - Distinct brain areas process novel and repeating tone sequences.
AB  - The auditory dorsal stream has been implicated in sensorimotor integration and
      concatenation of sequential sound events, both being important for processing of
      speech and music. The auditory ventral stream, by contrast, is characterized as
      subserving sound identification and recognition. We studied the respective roles
      of the dorsal and ventral streams, including recruitment of basal ganglia and
      medial temporal lobe structures, in the processing of tone sequence elements. A
      sequence was presented incrementally across several runs during functional
      magnetic resonance imaging in humans, and we compared activation by sequence
      elements when heard for the first time ("novel") versus when the elements were
      repeating ("familiar"). Our results show a shift in tone-sequence-dependent
      activation from posterior-dorsal cortical areas and the basal ganglia during the
      processing of less familiar sequence elements towards anterior and ventral
      cortical areas and the medial temporal lobe after the encoding of highly familiar
      sequence elements into identifiable auditory objects.

PMID- 30278993
TI  - Implementation of infection control bundles in intensive care units: which
      parameters are applicable in low-to-middle income countries?

PMID- 30278994
TI  - Modelling demographic impacts of a growing Arctic fishery on a seabird population
      in Canada and Greenland.
AB  - In Baffin Bay and Davis Strait, reports indicate that Northern Fulmars (Fulmarus
      glacialis) are vulnerable to bycatch in the fisheries for Greenland Halibut
      (Reinhardtius hippoglossoides). We modeled the potential current and future
      impacts the expanding halibut fishery may have on fulmar populations in the
      region using population viability analysis. By varying age-specific bycatch
      vulnerability, detectability, and the size of the at-risk population, we tested
      how different scenarios may influence population trajectories. From 2011 to 2015,
      the bycatch rate of fulmars was approximately 212 (SD +/- 111) individuals per
      year. This could cause declines (-12%) over three generations (66 years) at the
      three colonies closest to the fishing grounds. However, declines could be as high
      as -33% over this same period if unobservable bycatch is considered, and as low
      as -0.4% if bycatch is distributed among a larger population. Several
      uncertainties we modeled could be reduced by improving how bycatch data are
      recorded by at-sea observer programs.

PMID- 30278995
TI  - Differential expression of mTOR signaling pathway proteins in lichen planopilaris
      and frontal fibrosing alopecia.
AB  - Dysregulation of the mammalian target of rapamycin (mTOR) signaling pathway has a
      variety of effects on the immune system and stem cell proliferation. Lichen
      planopilaris (LPP) and frontal fibrosing alopecia (FFA) are inflammatory scalp
      conditions resulting in permanent alopecia, which are thought to be related to
      stem cell damage. Here we investigate the expression of mTOR signaling pathway
      proteins in human hair follicles of LPP and FFA patients. The expression of mTOR
      pathway proteins in biopsy specimens from lesional and non-lesional scalp areas
      of eight LPP and five FFA patients were compared to control scalp biopsies from
      patients undergoing surgical excisions of sebaceous cysts. We performed
      immunohistochemical evaluation using a panel of antibodies including mTOR,
      phospho-mTOR (Ser2448), phospho-p70S6K (Thr389), phospho-4EBP1 (Thr37146), and
      phospho-tuberin (T1462), as well as Western blot analysis for phospho-p70S6K
      (Thr389) expression. All evaluated mTOR pathway proteins were similarly expressed
      in the control and patient non-lesional scalps. While mTOR expression did not
      show significant alterations between the groups, p-mTOR, p-p70S6K, p-4EBP1, and p
      tuberin expressions decreased in the interfollicular epidermis in the lesional
      scalps of patients. p-p70S6K and p-4EBP1 expression decreased in the outer root
      sheath (ORS) and inner root sheath (IRS) of the bulge of hair follicles in the
      lesional scalps of patients. p-mTOR and p-p70S6K expression increased in the
      lower follicle ORS and bulb of the hair follicles, and p-4EBP1 expression
      decreased in the bulb of the hair follicles in the lesional scalps of patients.
      Phospho-tuberin expression increased in the IRS of the bulge and lower follicle
      ORS of the hair follicles in the lesional scalps of patients, whereas its
      expression decreased in the bulb. Our results indicate that the mTOR signaling
      pathway proteins are localized throughout normal hair follicles and that
      expression of mTOR signaling pathway proteins is altered in the hair follicles of
      LPP and FFA patients. Further research is required to understand the mechanism by
      which mTOR operates in the pathogenesis of these diseases.

PMID- 30278996
TI  - Impact of right upper quadrant cytoreductive techniques with extensive liver
      mobilization on postoperative hepatic function and risk of liver failure in
      patients with advanced ovarian cancer.
AB  - OBJECTIVE: Evaluate postoperative hepatic-function in patients with advanced
      ovarian cancer (OC) who underwent extensive right upper-quadrant (RUQ)
      cytoreduction in primary, relapsed or interval settings. METHODS: We
      retrospectively reviewed all patients with OC who underwent liver resection,
      mobilization and/or diaphragmatic-stripping between 01/2013 and 12/2016.
      Postoperative liver enzyme function (LFTs), assessed by alanine transaminase
      (ALT), alkaline phosphatase (ALP) and bilirubin (Bil), was correlated with
      postoperative complications. RESULTS: 132 patients were identified. 81 patients
      (61%) underwent upfront, 25(19%) interval and 26(20%) secondary cytoreduction.
      The surgical procedures were right diaphragmatic peritoneal stripping
      (81/132;61%), full-thickness resection (42/132;32%), liver-capsule resection
      (85/132;64%), porta-hepatis tumor resection (11/132;8%) and partial hepatectomy
      (5/132;4%). 74%(98/132) of patients increased their LFTs postoperatively with a
      peak at 24-hours. Highest ALT median was 1.7-fold of upper normal limit (UNL),
      with the highest ALT value rising up to 28-fold UNL on the 1st postoperative day
      (PoD)(range 6-1792 IU/L). Median value of highest ALP was within normal, with the
      highest ALP value rising up to 4-fold UNL on PoD 5(range 22-512 IU/L). Median
      value of highest Bilirubin level was also within normal, with highest Bilirubin
      level rising up to 6-fold UNL on PoD 5(range: 2-120 MUmol/L). Mean LFT
      normalization time was 7 days (range: 3-14 days). No significant morbidity was
      directly linked to LFT deterioration, apart from one case (0.8%) of fatal
      fulminant hepatic-failure. CONCLUSION: RUQ-cytoreduction is almost always
      associated with a transient LFT-increase, with no significant clinical
      implications and spontaneous normalization within the first postoperative week.
      Due to the existing risk of fulminant liver failure, albeit rare and difficult to
      predict, postoperatively elevated LFTs should be monitored, until normalization.
      Large prospective studies are required to assess the predictive value of LFTs and
      other risk factors for postoperative hepatic failure in patients with OC
      undergoing extensive RUQ-cytoreduction.

PMID- 30278997
TI  - Programmed cell death ligand 1 expression is upregulated in the skeletal muscle
      of patients with myasthenia gravis.
AB  - We investigated the expression patterns of programmed cell death-ligand 1 (PD-L1)
      in the skeletal muscle of 15 patients with myasthenia gravis (MG). In 11 of the
      patients, immunohistochemistry confirmed the localization of PD-L1 in the muscle
      cell membrane with cytoplasmic integrity. PD-L1 mRNA expression levels were
      higher in the muscles of MG patients as compared to those of non-myogenic
      patients (p < .05). Moreover, a unimodal relationship between PD-L1 mRNA levels
      and quantitative MG scores for disease severity was identified by a generalized
      additive model, indicating reciprocal effects. Together, these results suggest
      that MG symptoms might influence PD-L1 expression in muscle cells, and
      upregulated PD-L1 expression might inhibit autoimmune reactivity.

PMID- 30278998
TI  - Is STM involved in sentence comprehension?
AB  - We discuss the literature concerning the role of auditory-verbal short-term
      memory (phonological loop) in sentence comprehension. We critically analyze data
      concerning patients with a selective deficit of the phonological loop, then we
      examine aphasic patients with deficit of auditory-verbal short-term memory and we
      consider the effect of STM treatment on sentence comprehension. Finally, results
      from imaging and TMS studies are discussed. In our opinion, data from the
      literature suggest that both components of the phonological loop are involved in
      the comprehension of some type of sentence, namely syntactically complex
      sentences that load on memory, such as center-embedded object relative clauses.
      However, it is crucial to investigate further patients with a selective STM
      impairment or aphasic patients, by using extensive and sophisticated experimental
      material.

PMID- 30278999
TI  - The patient said he would rather die: Should you let him?

PMID- 30279000
TI  - Surgical myectomy versus alcohol septal ablation for obstructive hypertrophic
      cardiomyopathy: A propensity score-matched cohort.
AB  - OBJECTIVES: In patients with hypertrophic cardiomyopathy, obstruction of the left
      ventricular outflow tract can be relieved by surgical septal myectomy or alcohol
      septal ablation, but uncertainty remains regarding long-term results and
      comparative effectiveness of alcohol septal ablation. This study aims to compare
      short- and long-term outcomes of the 2 procedures. METHODS: Between December 1998
      and September 2016, 2407 patients underwent septal myectomy and 211 patients
      underwent alcohol septal ablation at our institution. After 2:1 propensity score
      matching, the study cohort included 334 patients who underwent myectomy and 167
      patients who underwent alcohol septal ablation. RESULTS: Median (interquartile
      range) ages of patients in the myectomy and alcohol septal ablation groups were
      65 (58-71) years and 64 (56-73) years (P = .9), respectively. After intervention,
      median resting left ventricular outflow tract gradient at predischarge
      transthoracic echocardiography was 0 (0-10) mm Hg in the myectomy group (n = 288)
      and 21 (10-60) mm Hg in the alcohol septal ablation group (n = 63) (P < .001,
      tested at baseline gradients of 30 and 50 mm Hg). There were no differences in
      survival between the 2 groups (risk of death for alcohol septal ablation vs
      myectomy, hazard ratio, 1.5; 95% confidence interval, 0.9-2.6; P = .1). Survival
      of patients undergoing septal myectomy was better than that of an age-, sex-, and
      race-matched US population (82% vs 75% at 12 years, P = .01). Reintervention for
      left ventricular outflow tract obstruction was more likely to occur in patients
      who received alcohol septal ablation (hazard ratio, 33.3; 95% confidence
      interval, 4.4-250.6; P < .001). CONCLUSIONS: There were no differences in
      survival of patients undergoing myectomy or alcohol septal ablation, but freedom
      from reintervention and early and late reduction of left ventricular outflow
      tract gradient are superior in patients undergoing septal myectomy.

PMID- 30279001
TI  - Potential roles of neurotensin on cognition in conditions of obese-insulin
      resistance.
AB  - Neurotensin is an endogenous tridecapeptide that can be found in both central and
      peripheral nervous systems. Under normal physiological conditions, neurotensin is
      involved in the regulation of pain, body temperature, physical activity, appetite
      as well as learning and memory. In addition, it plays an important role in fat
      metabolism. Previous studies have demonstrated that alterations of neurotensin
      levels were associated with several neuropathological conditions such as
      Alzheimer's disease, mood disorders, and obesity associated eating disorders.
      Obesity has been shown to be associated with low-grade systemic inflammation,
      brain inflammation, and cognitive decline. Several pieces of evidence suggest
      that neurotensin might play a role in cognitive decline following obesity.
      However, the underlying mechanisms of neurotensin on cognition under obese
      insulin resistant condition are still unclear. In this review, the current
      available evidence from in vitro, in vivo and clinical studies regarding the role
      of neurotensin in the physiological condition and obesity in association with
      cognition are comprehensively summarized and discussed. The studies which report
      controversial findings regarding these issues are also presented and discussed.

PMID- 30279002
TI  - Machine learning in human movement biomechanics: Best practices, common pitfalls,
      and new opportunities.
AB  - Traditional laboratory experiments, rehabilitation clinics, and wearable sensors
      offer biomechanists a wealth of data on healthy and pathological movement. To
      harness the power of these data and make research more efficient, modern machine
      learning techniques are starting to complement traditional statistical tools.
      This survey summarizes the current usage of machine learning methods in human
      movement biomechanics and highlights best practices that will enable critical
      evaluation of the literature. We carried out a PubMed/Medline database search for
      original research articles that used machine learning to study movement
      biomechanics in patients with musculoskeletal and neuromuscular diseases. Most
      studies that met our inclusion criteria focused on classifying pathological
      movement, predicting risk of developing a disease, estimating the effect of an
      intervention, or automatically recognizing activities to facilitate out-of-clinic
      patient monitoring. We found that research studies build and evaluate models
      inconsistently, which motivated our discussion of best practices. We provide
      recommendations for training and evaluating machine learning models and discuss
      the potential of several underutilized approaches, such as deep learning, to
      generate new knowledge about human movement. We believe that cross-training
      biomechanists in data science and a cultural shift toward sharing of data and
      tools are essential to maximize the impact of biomechanics research.

PMID- 30279003
TI  - Refining Early Antitumoral Drug Development.
AB  - The failure rate of development of new drugs in oncology is high, with up to 95%
      of drugs tested in Phase I not reaching the market. Causes behind this high
      failure rate are discussed here, and solutions to increase the success in the
      development of antitumor drugs are suggested.

PMID- 30279004
TI  - FGL2 prothrombinase contributes to the early stage of coronary microvascular
      obstruction through a fibrin-dependent pathway.
AB  - BACKGROUND: Membrane-associated fibrinogen-like protein 2 (FGL2 prothrombinase,
      pFGL2) is abundantly expressed in activated microvascular endothelial cells
      (MVECs) and plays a crucial role in microthrombus formation in microcirculatory
      vasculature. It has been widely reported that coronary microvascular obstruction
      (CMVO) contributes to adverse outcomes following myocardial ischemia/reperfusion.
      However, the role of pFGL2 in CMVO is poorly understood. METHODS AND RESULTS: We
      aimed to identify the effect of MVECs-pFGL2 in CMVO using FGL2 knockout mice. As
      results, the MVECs-pFGL2 expression progresses significantly over 3 days and then
      gradually decreases, which is positively correlated with the extent of CMVO as
      detected by HE staining in wild type mice. Furthermore, FGL2 deficiency is
      correlated with decreased areas of no-reflow and necrosis as detected by Evans
      Blue and TTC staining and that it ameliorates cardiac dysfunction detected by
      hemodynamics in the early stage of CMVO. Moreover, fibrin deposition in
      microvasculature is significantly reduced in FGL2-deficient mice as evidenced by
      immunohistochemistry, MSB and Carstairs staining, along with the down-regulation
      of leukocyte adhesion and infiltration. Additionally, we observed that the FGL2
      deficiency decreases macrophage infiltration and shifts the macrophage phenotype
      from pro-inflammatory (M1,) to anti-inflammatory (M2,) pattern in the early stage
      of CMVO. CONCLUSION: These findings highlight the MVECs-pFGL2-fibrin pathway in
      the early stage of CMVO and provide insights into coagulation and inflammation
      for the coronary artery disease therapeutics.

PMID- 30279006
TI  - Classification of craniofacial osteoradionecrosis: the addition of "end stage
      disease".

PMID- 30279007
TI  - Sublingual gland flap for soft tissue reconstruction of oral defects.

PMID- 30279005
TI  - Sarcomere-based genetic enhancement of systolic cardiac function in a murine
      model of dilated cardiomyopathy.
AB  - Diminished cardiac contractile function is a characteristic feature of dilated
      cardiomyopathy (DCM) and many other heart failure (HF) causing etiologies. We
      tested the hypothesis that targeting the sarcomere to increase cardiac
      contractility can effectively prevent the DCM phenotype in muscle-LIM protein
      knockout (MLP-/-) mice. The ablation of cardiac myosin binding protein C (MYBPC3
      /-) protected the MLP-/- mice from developing the DCM phenotype. We examined the
      in vivo cardiac function and morphology of the resultant mouse model lacking both
      MLP and MYBPC3 (DKO) by echocardiography and pressure-volume catheterization and
      found a significant reduction in hypertrophy, as evidenced by normalized wall
      thickness and chamber dimensions, and improved systolic function, as evidenced by
      enhanced ejection fraction (~26% increase compared MLP-/- mice) and rate of
      pressure development (DKO 7851.0 +/- 504.8 vs. MLP-/- 4496.4 +/- 196.8 mmHg/s).
      To investigate the molecular basis for the improved DKO phenotype we performed
      mechanical experiments in skinned myocardium isolated from WT and the individual
      KO mice. Skinned myocardium isolated from DKO mice displayed increased Ca2+
      sensitivity of force generation, and significantly accelerated rate of cross
      bridge detachment (+63% compared to MLP-/-) and rate of XB recruitment (+58%
      compared to MLP-/-) at submaximal Ca2+ activations. The in vivo and in vitro
      functional enhancement of DKO mice demonstrates that enhancing the sarcomeric
      contractility can be cardioprotective in HF characterized by reduced cardiac
      output, such as in cases of DCM.

PMID- 30279008
TI  - [Von Willebrand disease].
AB  - Von Willebrand factor is involved in primary hemostasis (adhesion of platelets to
      subendothelium and platelet aggregation) and acts as the carrier of coagulation
      factor VIII. Von Willebrand disease, resulting from a quantitative or qualitative
      defect of this factor, is the most frequent inherited bleeding disorder. It is
      mainly responsible for symptoms such as mucocutaneous bleeding and excessive
      bleeding after trauma or invasive procedures, but can also cause gastro
      intestinal bleeding or hemarthrosis in the most severe forms of the disease.
      There are numerous causes of physiological variation of von Willebrand factor
      plasma levels which can be responsible for diagnostic difficulty or changes in
      symptoms over time. Diagnosis relies primarily on clinical symptoms but requires
      the use of several laboratory analyses: von Willebrand factor activity and
      antigen testing and factor VIII activity. More specialized assays allow
      classification of the disease in various types and subtypes which imply different
      management strategies (types 1, 2A, 2B, 2M, 2N, and 3). Treatment is based on
      desmopressin, responsible for an increase in plasma concentration of von
      Willebrand factor, and plasma-derived von Willebrand factor concentrates which
      can be combined with factor VIII.

PMID- 30279009
TI  - Successful angioembolization treatment in a patient with a mechanical heart valve
      with hemorrhagic corpus luteum.

PMID- 30279010
TI  - LncRNA TP73-AS1 accelerates tumor progression in gastric cancer through
      regulating miR-194-5p/SDAD1 axis.
AB  - BACKGROUND: Long noncoding RNAs (lncRNAs) have been considered as significant
      regulators in many cancer progression, such as proliferation, invasion and other
      path of evolution. Nevertheless, we have not had a grasp of the role of lncRNA
      TP73-AS1 in gastric cancer (GC). METHODS: qRT-PCR analysis was first conducted to
      examine the TP73-AS1 level in both GC tissues and cell lines. Then gain or loss
      of-function assays were carried out to detect the effect of TP73-AS1 on GC
      development. In mechanism, bioinformatics analysis and luciferase reporter assays
      were used to search and confirm the target gene of TP73-AS1. Finally, rescue
      assays were performed to confirm the influence of TP73-AS1-miR-194-5p-SDAD1 axis
      on GC development. RESULTS: TP73-AS1 was upregulated in GC tissues and cell
      lines. Furthermore, TP73-AS1 exerted oncogenic role in GC through promoting cell
      growth and metastasis. In addition, TP73-AS1 was certified as a ceRNA by
      regulating miR-194-5p/SDAD1 axis. CONCLUSIONS: TP73-AS1 accelerates tumor
      progression in gastric cancer through regulating miR-194-5p/SDAD1 axis.

PMID- 30279011
TI  - Extrapolation of Normative KOOS, JR Data for the Young Patient Population
      Undergoing Knee Arthroplasty Procedures.
AB  - BACKGROUND: The Knee Injury and Osteoarthritis Outcome (KOOS), JR is a patient
      reported outcome measure that is validated for patients undergoing total knee
      arthroplasty. The objective of this study was to provide normative data for the
      KOOS, JR in a relatively healthy US population visiting an outpatient orthopedic
      setting. This study is a cross-sectional study. METHODS: Normative data from the
      KOOS questionnaire was used to calculate the subscale (pain, activity of daily
      living, and symptoms), raw, and interval scores for the KOOS, JR. The
      participants who completed the KOOS were devoid of current complaints of the hip,
      knee, and ankle. The means, standard deviations, medians, interquartile ranges,
      and percentiles for the KOOS, JR subscale, raw and interval scores were
      calculated by age decades, sex, laterality, and history of knee injuries in the
      past year. RESULTS: Four hundred two men and 598 women were involved in the
      analysis. The lowest mean interval scores were noted in the 56- to 64-year group
      with the greatest disparity between male and female compared to the rest of the
      age cohorts. Females scored high in all 3 subscales with a higher score in the
      pain subscale, denoting a lower normative value. Patients with hypertension
      scored with a significantly lower mean interval score than those without
      hypertension. In all subscales, tobacco use and hypertension were associated with
      a statistically significant negative effect on the normative scores. CONCLUSION:
      The normative values for the KOOS, JR can be used to set goals and follow the
      progress of patient satisfaction in regard to the knee after a knee arthroplasty
      procedure.

PMID- 30279012
TI  - Response to Letter to the Editor on "Comparing the Effect of Tourniquet vs.
      Tourniquet-Less in Simultaneous Bilateral Total Knee Arthroplasties".

PMID- 30279013
TI  - ?

PMID- 30279014
TI  - [Could we call frequent attenders to patients because of their high frequency of
      attendance?]

PMID- 30279015
TI  - BOXIT-A Randomised Phase III Placebo-controlled Trial Evaluating the Addition of
      Celecoxib to Standard Treatment of Transitional Cell Carcinoma of the Bladder
      (CRUK/07/004).
AB  - BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) has a significant risk of
      recurrence despite adjuvant intravesical therapy. OBJECTIVE: To determine whether
      celecoxib, a cyclo-oxygenase 2 inhibitor, reduces the risk of recurrence in NMIBC
      patients receiving standard treatment. DESIGN, SETTING, AND PARTICIPANTS: BOXIT
      (CRUK/07/004, ISRCTN84681538) is a double-blinded, phase III, randomised
      controlled trial. Patients aged >=18 yr with intermediate- or high-risk NMIBC
      were accrued across 51 UK centres between 1 November 2007 and 23 July 2012.
      INTERVENTION: Patients were randomised (1:1) to celecoxib 200mg twice daily or
      placebo for 2 yr. Patients with intermediate-risk NMIBC were recommended to
      receive six weekly mitomycin C instillations; high-risk NMIBC cases received six
      weekly bacillus Calmette-Guerin and maintenance therapy. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: The primary endpoint was time to disease recurrence.
      Analysis was by intention to treat. RESULTS AND LIMITATIONS: A total of 472
      patients were randomised (236:236). With median follow-up of 44 mo (interquartile
      range: 36-57), 3-yr recurrence-free rate (95% confidence interval) was as
      follows: celecoxib 68% (61-74%) versus placebo 64% (57-70%; hazard ratio [HR]
      0.82 [0.60-1.12], p=0.2). There was no difference in high-risk (HR 0.77 [0.52
      1.15], p=0.2) or intermediate-risk (HR 0.90 [0.55-1.48], p=0.7) NMIBC. Subgroup
      analysis suggested that time to recurrence was longer in pT1 NMIBC patients
      treated with celecoxib compared with those receiving placebo (HR 0.53 [0.30
      0.94], interaction test p=0.04). The 3-yr progression rates in high-risk patients
      were low: 10% (6.5-17%) and 9.7% (6.0-15%) in celecoxib and placebo arms,
      respectively. Incidence of serious cardiovascular events was higher in celecoxib
      (5.2%) than in placebo (1.7%) group (difference +3.4% [-0.3% to 7.2%], p=0.07).
      CONCLUSIONS: BOXIT did not show that celecoxib reduces the risk of recurrence in
      intermediate- or high-risk NMIBC, although celecoxib was associated with delayed
      time to recurrence in pT1 NMIBC patients. The increased risk of cardiovascular
      events does not support the use of celecoxib. PATIENT SUMMARY: Celecoxib was not
      shown to reduce the risk of recurrence in intermediate- or high-risk non-muscle
      invasive bladder cancer (NMIBC), although celecoxib was associated with delayed
      time to recurrence in pT1 NMIBC patients. The increased risk of cardiovascular
      events does not support the use of celecoxib.

PMID- 30279016
TI  - [Tuberculosis in older persons in African setting: Epidemiological, diagnostic
      and evolutive features].
AB  - OBJECTIVE: To determine the epidemiological, diagnostic and evolutives features
      of tuberculosis (TB) in older subjects in Benin. PATIENTS AND METHODS: This was a
      retrospective cohort study of adults TB patients (age>=15 years) who were
      notified at all the Basic Management Units (BMU) in Benin from January 1st, 2013
      to December 31st. Older subjects (age>=60 years) were compared to those less than
      60 years named young subjects. The threshold of significance was set at 5%.
      RESULTS: The analysis was carried out on 6531 cases adults cases notified during
      the period. 601 (9.2%) were 60 years old or above. The case notification rate
      (CNR) in elders was more than twice the CNR in young people (68 cases vs. 31
      cases per 100,000 population). Older subjects were less often infected with HIV
      (9.3%) than young's (16.7%), P<0.0001. In new bacteriologically confirmed
      pulmonary TB negative for HIV, unfavorable treatment outcomes were more frequent
      in older subjects than in young subjects with more deaths (7.5% vs. 3.0%). On the
      other hand, in bacteriological confirmed TB seropositive for HIV and all the
      other cases, treatment outcomes were comparable between the two groups.
      CONCLUSION: The high CNR and the high death rate in older subjects should plead
      for a specific care for an adapted management of TB case in this group.

PMID- 30279017
TI  - Incidence and predictors of health care-associated infections among patients
      colonized with carbapenem-resistant Enterobacteriaceae.
AB  - Colonization with carbapenem-resistant Enterobacteriaceae (CRE) precedes invasive
      infections. Neither the actual risk for the latter nor the route between the 2
      stages is completely clear. We studied a retrospective cohort of patients
      hospitalized between 2013-2016 and colonized with CRE. The incidence of CRE
      health care-associated infections was 13.2%, and predictors were the presence of
      a urinary catheter and the use of carbapenems. Infection prevention strategies in
      CRE-colonized patients should focus on invasive devices and antimicrobial
      stewardship.

PMID- 30279018
TI  - High incidence of persistent subtherapeutic levels of the most common AEDs in
      children with epilepsy receiving polytherapy.
AB  - BACKGROUND: Low levels of AEDs can be secondary drug-drug interactions or related
      to irregular intake due to poor treatment adherence. This latter behavior is
      highly suspected in ambulatory pediatric epileptic patients when controls of AEDs
      are subtherapeutic. However, it cannot be considered for inpatients during long
      periods of hospitalization. A few isolated case reports have documented
      persistent low levels (PLL) of AEDs in hospitalized epileptic children, but no
      population study has currently been reported. OBJECTIVE: The aim of this study
      was to document the incidence of PLL of the most common AEDs - phenytoin (PHT),
      phenobarbital (PHB), valproic acid (VA), and carbamazepine (CBZ) - in pediatric
      epileptic in- and outpatients (PEP). METHODS: 21,040 plasma levels of the
      aforementioned AEDs from 3279 PEP were retrospectively analyzed. Plasma levels of
      AEDs were measured by an automated method using trademarked commercial kits with
      their corresponding quality control programs. Randomized samples were also
      controlled by HPLC methods. Only cases with more than 3 controls were included in
      the study. RESULTS: A high rate of PLL of PHT was detected in in- (71.7%) and
      outpatients (74.1%), while PLL of PHB, VA, and CBZ were detected in a lower
      proportion. Rates of PLL of PHT were similar in in- and outpatients. PLL of PHB
      was more commonly observed in outpatients while PLL of VA and CBZ were more
      frequently seen in inpatients. In some hospitalized patients receiving
      polytherapy, PLL of at least one AED were documented during a long time.
      DISCUSSION: Treatment non-adherence could be present in part of the outpatients,
      but cannot explain the PLL observed in a group of inpatients as described here.
      The recently described "pharmacokinetic hypothesis" of pharmaco-resistant
      epilepsy should be addressed in cases with AEDs-PLL, particularly in hospitalized
      cases. Perhaps, instead of stopping the subtherapeutic medication, the increasing
      doses of this AED and/or administration of inhibitors of CYP and P-glycoprotein,
      could help to achieve its therapeutic range, allowing a better pharmacologic
      effect and avoiding the development of more severe complications, such as status
      epilepticus or SUDEP.

PMID- 30279019
TI  - Relationship between lean body mass and isokinetic peak torque of knee extensors
      and flexors in severely burned children.
AB  - OBJECTIVE: Severe burns cause hypermetabolic responses and prolonged
      hospitalization, resulting in loss of body mass and muscle strength. This study
      aimed to determine whether long-term gains in lean body mass (LBM) after
      structured exercise programs are functionally meaningful and related to greater
      muscle strength in severely burned children. STUDY DESIGN: LBM and muscle
      strength were measured at discharge and at 6, 12, 24, and 36 months after burn in
      349 children. Body composition, including LBM, was measured via dual-emission X
      ray-absorptiometry. Peak torque was measured using Biodex dynamometer at varying
      angular velocities (90, 120, 150, 180 degrees /s). Pearson correlation analysis
      evaluated the association between LBM and peak torque. RESULTS: LBM progressively
      increased from discharge (32.5+/-11.5kg) to 36 months following injury (40.2+/
      12.3kg). Peak torque and peak torque/LBM increased from discharge (56.4+/-34.0Nm
      and 1.7+/-34.0Nmkg-1) to 36 months after burn (102.3+/-43.8Nm and 2.5+/-0.7Nmkg
      1, p<0.01 for both). LBM and peak torque at all angular velocities showed
      moderate/strong correlations, with 120 degrees /s being the strongest (all time
      points: R2>=0.57). CONCLUSION: In severely burned children participating in a
      rehabilitative exercise program, gains in LBM over time are related to increases
      in muscle strength, suggesting that gained muscle mass is functional. Measurement
      of muscle strength at an angular velocity of 120 degrees /s best reflects gains
      in LBM and should be considered for reliable measure of strength in future
      studies.

PMID- 30279020
TI  - Place identity, autobiographical memory and life path trajectories: The
      development of a place-time-identity model.
AB  - The ability to remember, recognize and reconstruct places is a key component of
      episodic autobiographical memory. In this respect, place forms an essential basis
      for the unfolding of experiences in memory and imagination. The autobiographical
      memory is seen to contribute to a sense of self and place identity. The aim of
      this study was to concertedly analyze paintings, autobiographical narrations and
      places of birth and life of clients under treatment at a psychiatric clinic in
      Switzerland who were manifesting psychiatric disorders, e.g. depression, anxiety
      disorders, bipolar disorder, personality disorder, substance dependence, and
      dementia. Each client exhibited distinctive attitudes and approaches towards life
      characterized by unique personal mental constructs for living in given places of
      time episodes that worked towards shaping the development of their identities as
      well as the development of their health. For these clients, place and time
      function together to leave a mark, a trajectory, that can hinder or help the
      resolution of a psychiatric condition. Based on six representative cases, we
      illustrate how each painting, each biographical narration and each interview
      reveals deeper structures of individual perception, emotions, feelings, coping
      strategies, and capacities to reflect and identify with place-time trajectories.
      Based on this analysis, a place-time-identity model has been developed, which
      emphasizes the importance of narration, the structure of personality, and
      emotional experiences in the development of the 'relay station' of episodic
      autobiographical memory, self and autonoetic consciousness: these three elements
      are not only connected through their embeddedness in time, but also through their
      embeddedness in place. In this context, place provides an external fundus of
      memory, capable of supporting humans in healthy recollection and remembering. The
      process of placing appears to contribute to the creation of self-esteem and
      identity. This psycho-geographical place-life-time approach is contrasted to
      phenomenological place-space-time theories of Husserl, Heidegger, Bachelard, and
      Sloterdijk.

PMID- 30279021
TI  - Healthcare providers' caring for Thai teenage parents: A focus group study.

PMID- 30279022
TI  - Corrigendum to "Effects of Xiao Yao San on interferon-alpha-induced depression in
      mice" [Brain Res. Bull. 139 (2018) 197-202].

PMID- 30279023
TI  - A Clinical Practice Perspective on Publishing in Oncology Nursing.
AB  - OBJECTIVE: To describe how clinical problems and observations can generate ideas
      for writing for publication. DATA SOURCES: Journal articles, publishers'
      information for authors, online publishing resources, personal experience.
      CONCLUSION: Ideas for publishable manuscripts can be generated from clinical
      practice dilemmas, patient or nursing outcome data, and reading professional
      materials or attendance at professional meetings. Publishing opportunities for
      novice writers include case reports, letters to editors, abstracts for
      professional conferences, and articles in a variety of newsletters and journals.
      IMPLICATIONS FOR NURSING PRACTICE: Nurses working in clinical practice settings
      have a wealth of opportunities for identifying topics suitable for publication.

PMID- 30279024
TI  - Daptomycin for the treatment of Staphylococcus aureus infections complicated by
      septic pulmonary emboli.
AB  - The management of Staphylococcus aureus bacteremia is limited by high rates of
      methicillin resistance and the paucity of antibiotic agents with proven efficacy
      in complicated infectious syndromes, such as endocarditis. Vancomycin is the
      mainstay of therapy; however, salvage therapy is frequently required due to
      persistence of infection or drug toxicity. Daptomycin is FDA-approved for S.
      aureus bacteremia and right-sided endocarditis, but controversy exists regarding
      the role of this agent in the setting of septic pulmonary emboli. Sequestration
      by pulmonary surfactant renders daptomycin ineffective in bronchoalveolar
      pneumonia; however, the impact of this drug property on efficacy in hematogenous
      pulmonary infections is unclear. Herein we review the available evidence in order
      to inform the rationale use of daptomycin in S. aureus infections complicated by
      septic pulmonary emboli.

PMID- 30279025
TI  - The performance of galactomannan in combination with 1,3-beta-D-glucan or
      aspergillus-lateral flow device for the diagnosis of invasive aspergillosis:
      Evidences from 13 studies.
AB  - Galactomannan (GM), 1,3-beta-D-glucan (BDG) and aspergillus-lateral flow device
      (LFD) are recognized as diagnostic tools for invasive aspergillosis (IA). The
      combined performance of these assays, however, is inconsistent in various
      studies. We undertook a meta-analysis of 13 studies involving 1513 patients to
      evaluate the utility of GM in combination with BDG or LFD for diagnosing IA. The
      pooled SEN, SPE, PLR, NLR and diagnostic odds ratio (DOR) were calculated and
      constructed to summarize the overall combined performance. Combining both
      positive results of GM and BDG assays leaded to the pooled SEN 0.49 (95%CI 0.27
      0.72), SPE 0.98 (95%CI 0.94-1.00), PLR 31.68 (95%CI 5.36-187.37), NLR 0.52 (95%CI
      0.32-0.84) and DOR 61.23 (95%CI 6.96-538.90). Comparing with GM and BDG assays,
      both positive results of GM and LFD leaded to high SEN, similar SPE, low PLR and
      NLR. At least one positive result of GM or LFD conferred great SEN 0.93 and low
      NLR 0.08. Both positive results of GM and BDG or LFD assay were in favor of
      confirming the existence of IA. And both negative results of GM and LFD were
      beneficial to rule out IA. Further studies with sufficient sample size should
      focus on the diagnostic performance and cost-effectiveness of these combined
      tests in clinical setting.

PMID- 30279026
TI  - Peri-follicular blood flow in the follicle from which ovulation occurs in cows.
AB  - The hypothesis of the study was that the vascularity of ovulatory follicles (OF)
      determines the ovulatory status. The peri-follicular blood flow characteristics
      of OF were sequentially recorded using Color Doppler Imaging ultrasonography from
      the onset of induced estrus (Day 0) to ovulation at 12 h intervals. The OFs were
      categorized into two groups based on the timing of ovulation (i) Normal ovulation
      (OFN) - When ovulation occurred within 36 h after the onset of estrus (n = 18)
      and (ii) Delayed ovulation (OFD) - When ovulation occurred after 36 h (n = 15).
      The blood flow velocity, Doppler pulse duration (DPD) and Pulsatility index (PI)
      of the OF were recorded during each examination. The OF was well vascularized
      with a detectable blood flow signals, while the subordinate or atretic follicles
      were devoid of detectable blood flow. On Day 0, the DPD (874.33 +/- 56.99 ms) and
      PI (0.62 +/- 0.01) values were less in the OFN when compared to OFD (1140.56 +/-
      27.54 ms and 1.28 +/- 0.15 respectively) group. In the OFD group, ovulation
      occurred between 36 and 60 h after onset of estrus when the DPD value reduced to
      878.17 ms. Based on ROC analysis, it was evident that the DPD value of < 929 ms
      is a necessary factor for induction of ovulation. The decreased DPD and PI values
      of the OF on the day of estrus are positive indicators of a normal ovulation
      process.

PMID- 30279027
TI  - Apoptosis and developmental capacity of vitrified parthenogenetic pig
      blastocysts.
AB  - This study was conducted to evaluate whether the poor developmental capacity of
      pig embryos after vitrification was related to the occurrence of apoptosis.
      Parthenogenetic blastocysts were used as the research material. The blastocoel
      recovery rate, mitochondrial membrane potential (DeltaPsim), amount of early
      apoptosis, activities of several caspases, and relative abundance of mRNA of
      apoptosis-related genes involved in mitochondria and death receptor apoptotic
      pathways were detected before or after vitrification. The results indicate that
      the blastocoel recovery rate (31.0%) and total cells (31.8) of vitrified
      blastocysts were less than those of fresh blastocysts (100% and 38.2, P <  0.05).
      The DeltaPsim of vitrified blastocysts was 0.46, which was less than that of
      fresh blastocysts (1.02, P <  0.05). The rate of apoptotic cells in vitrified
      blastocysts (8.1%) after TUNEL (TdT-mediated dUTP Nick-End Labeling) assay was
      markedly greater than that in fresh blastocysts (3.9%, P <  0.05). The pan
      caspase, caspase-3, caspase-8 and caspase-9 activities of vitrified blastocysts
      (20.7, 20.6, 17.6 and 19.9) were markedly greater than those of fresh blastocysts
      (7.4, 6.5, 5.5 and 6.3, P <  0.05). The real-time PCR results indicated that
      relative abundance of caspase-8 and TNF-alpha mRNA from death receptor apoptotic
      pathway and caspase-9 for the mitochondrial apoptotic pathway genes in the
      vitrified group were greater than those in the fresh group P <  0.05). The
      relative abundance of Bcl-2 and SOD-1 mRNA for the mitochondrial pathway genes in
      the vitrified group was less than those in the fresh group (P <  0.05). In
      conclusion, the poor developmental capacity of vitrified parthenogenetic pig
      blastocysts was closely related with apoptosis. Both mitochondria and death
      receptor-mediated apoptotic pathways participated the occurrence of this
      apoptosis.

PMID- 30279028
TI  - Patient education during hospital admission due to exacerbation of chronic
      obstructive pulmonary disease: Effects on quality of life-Controlled and
      randomized experimental study.
AB  - : The objective of this study was to assess the effectiveness of an education
      program and telephone call follow-up at improving the health related quality of
      life (HRQL) of patients with chronic obstructive pulmonary disease (COPD).
      METHOD: Experimental, controlled, randomized, single blind study, masked data
      analysis. Duration of 2 years and 3 months. Patients hospitalised for
      exacerbation. The effectiveness was evaluated by calculating the absolute and
      relative change (%) of the St. George questionnaire scores (total and by
      dimensions) before and after the intervention program. Calculation of the effect
      of the group variable on the absolute and relative changes of the variables,
      Multiple Analysis of Variance (MANOVA). RESULTS: Completed study of 116 patients.
      Greater effects on their HRQL reported at admission (48.3 +/- SD 20.0 years).
      Patients in the intervention group improved significantly in their total SGRQ
      scores (-6.83) in absolute and relative terms and more significantly in their
      activity dimension (-16.05). CONCLUSIONS: The education program was effective at
      improving global HRQL, especially the activity dimension, in exacerbated COPD
      patients. PRACTICE IMPLICATIONS: This research contributes to clarifying the
      benefits and contents of education programs for patients with COPD; hospital
      admission is the suitable moment to contact these patients.

PMID- 30279029
TI  - Behaviour change techniques applied in interventions to enhance physical activity
      adherence in patients with chronic musculoskeletal conditions: A systematic
      review and meta-analysis.
AB  - OBJECTIVE: To identify Behaviour Change Techniques (BCTs) applied in
      interventions to enhance physical activity (PA) adherence in patients with
      chronic musculoskeletal conditions and to investigate the effectiveness of these
      interventions in increasing PA adherence. METHODS: A systematic search of seven
      databases was conducted. We included (cluster/quasi-) randomised controlled
      trials comparing behaviour change interventions to no/placebo/minimal
      interventions or usual care and involving at least a three-month post
      intervention follow-up. Methodological quality was assessed, study
      characteristics and BCTs were narratively summarised and a meta-analysis was
      conducted. RESULTS: Across 22 included studies, we coded 8-18 BCTs (mean = 11.2)
      in intervention and 0-12 (mean = 3.5) in control groups. Common BCTs were "graded
      tasks", "goal setting", "self-monitoring", "problem solving" and "feedback". Meta
      analyses of 17 studies revealed a small medium-term effect (3-6 months post
      intervention, standardised mean difference (SMD) = 0.20, 95% CI 0.08-0.33) and no
      long-term effect (7-12 months post-intervention, SMD = 0.13, 95% CI -0.02 to
      0.28). Subgroup analysis yielded a higher effect (SMD = 0.29, 95% CI 0.19-0.40)
      for interventions using a greater number of BCTs. CONCLUSION: There is moderate
      quality evidence that interventions using BCTs are effective to enhance medium
      term physical activity adherence. PRACTICE IMPLICATION: While superiority of
      single BCTs was not shown, it is likely that using more BCTs results in better
      adherence.

PMID- 30279030
TI  - Is sarcopenia associated with hepatic encephalopathy in liver cirrhosis? A
      systematic review and meta-analysis.
AB  - BACKGROUND/PURPOSE: Hepatic encephalopathy (HE), a major neuropsychiatric
      complication in advanced liver disease, is associated with poor prognosis.
      Sarcopenia, characterized by a decline in muscle mass, strength, and physical
      performance, is prevalent in liver cirrhosis. This study aims to explore whether
      sarcopenia is associated with HE in cirrhotic patients. METHODS: PubMed and
      EMBASE were searched for relevant cohort and case-control studies investigating
      the association between sarcopenia and HE up to July 2018. Data of patients'
      characteristics, definition of low muscle mass, and protocols of
      grading/diagnosing HE were retrieved. The primary outcome was estimated by a
      pooled odds ratio (OR) and its 95% confidence interval (CI), using a random
      effect model. RESULTS: The meta-analysis enrolled 6 studies, comprising 1795
      patients. Sarcopenia was positively associated with the presence of HE (OR 2.74
      with a 95% CI, 1.87 to 4.01). The association was less likely to be influenced by
      differences in research designs, focused study outcomes, muscle mass
      measurements, and protocols of grading/diagnosing HE. There was lack of evidence
      supporting higher serum ammonia levels in patients with sarcopenia. CONCLUSION:
      In patients with liver cirrhosis, there is a significant association between
      sarcopenia and HE. A greater number of prospective studies are necessary to
      clarify whether the association remains even after adjusting relevant confounders
      and to suggest effective prevention of HE in patients with coexisting sarcopenia.

PMID- 30279031
TI  - Bacillus Calmette-Guerin vaccination-associated axillary lymphadenopathy in a 2
      year-old girl: Case report.

PMID- 30279033
TI  - Sonoelastography for the Assessment of Muscle Changes in Amyotrophic Lateral
      Sclerosis: Results of a Pilot Study.
AB  - The purpose of this study was to assess the sonoelastographic features of four
      different muscles in patients with amyotrophic lateral sclerosis compared with
      healthy controls and to evaluate the relationship of these features to muscle
      strength and other ultrasonographic variables. Fourteen patients with amyotrophic
      lateral sclerosis and 20 controls were examined using strain sonoelastography
      scanning. The RGB channel fraction ratio was analyzed with ImageJ software
      (Version 1.48). Two main sonoelastographic patterns could be distinguished in the
      controls: a clear predominance of the blue channel (hard areas) and a more
      heterogeneous pattern with predominance of the green channel (intermediate
      stiffness). These patterns were also observed in patients, although a higher
      green channel score was observed in mildly impaired muscles, whereas a higher
      blue channel score was observed in the most severely impaired muscle.
      Sonoelastography may be a good complementary biomarker in the detection and
      monitoring of muscle changes in amyotrophic lateral sclerosis.

PMID- 30279034
TI  - Interventional pulmonology techniques in elderly patients with comorbidities.
AB  - Respiratory diseases are common cause of disability in the elderly and are often
      concomitant with other non-respiratory medical conditions. Interventional
      pulmonology includes advanced diagnostic and therapeutic techniques, successfully
      employed for benign and malignant pulmonary diseases with a good safety profile.
      A few studies are available on the efficacy and the safety of these procedures
      (both bronchoscopic and pleural techniques) in the elderly. Paucity of data in
      these patients may support reluctant clinicians. We carried out a non-systematic
      review aimed at describing the scientific literature on interventional
      pulmonology techniques in elderly patients with comorbidities. We summarized
      indications, performance characteristics, and safety profile of bronchoscopic
      techniques in the elderly, comparing outcomes between older and younger patients.
      We explored the role of age on anesthesia and sedation protocols during
      endoscopic procedures and assessed the influence of comorbidities on
      bronchoscopic outcomes. This review underlines that older age is not a barrier
      for implementing interventional pulmonology for diagnostic and therapeutic
      purposes.

PMID- 30279032
TI  - Integrated Histotripsy and Bubble Coalescence Transducer for Thrombolysis.
AB  - After the collapse of a cavitation bubble cloud, residual microbubbles can
      persist for up to seconds and function as weak cavitation nuclei for subsequent
      pulses in a phenomenon known as cavitation memory effect. In histotripsy, the
      cavitation memory effect can cause bubble clouds to repeatedly form at the same
      discrete set of sites. This effect limits the efficacy of histotripsy-based
      tissue fractionation. Our previous studies have indicated that low-amplitude
      bubble-coalescing (BC) ultrasound sequences interleaved with high-amplitude
      histotripsy pulses can coalesce the residual bubbles into one large bubble
      quickly. This reduces the cavitation memory effect and may increase treatment
      efficacy. Histotripsy has been investigated for thrombolysis by breaking up clots
      into debris smaller than red blood cells. However, this treatment has low
      efficacy for aged or retracted clots. In this study, we investigate the use of
      histotripsy with BC to improve the efficacy of treatment of retracted clots. An
      integrated histotripsy and bubble-coalescing (HBC) transducer system with
      specialized electronic driving system was built in-house. One high-amplitude (32
      MPa), one-cycle histotripsy pulse followed by 36 low-amplitude (2.4 MPa), one
      cycle BC pulses formed one HBC sequence. Results indicate that HBC sequences
      successfully generated a flow channel through the retracted clots at scan speeds
      of 0.2-0.5 mm/s. The channel size created using the HBC sequence was 128% to 480%
      larger than that created using histotripsy alone. The clot debris particles
      generated during HBC treatments were within the tolerable range. These results
      illustrate the concept that BC improves the treatment efficacy of histotripsy
      thrombolysis for retracted clots.

PMID- 30279035
TI  - English and Italian national health services: Time for more patient-centered
      primary care?

PMID- 30279036
TI  - Growing number of incident pulmonary arterial hypertension and chronic
      thromboembolic pulmonary hypertension patients in Latvia: a shifting
      epidemiological landscape? Data from a national pulmonary hypertension registry.

PMID- 30279037
TI  - Corrigendum to "Design and synthesis of novel thiadiazole-thiazolone hybrids as
      potential inhibitors of the human mitotic kinesin Eg5 [Bioorg Med Chem Lett 28
      (17) (2018) 2930-2938]".

PMID- 30279038
TI  - Radiological Kinetics of Brain Metastases and Clinical Implications for Patients
      Treated With Stereotactic Radiosurgery.
AB  - AIMS: Select patients with brain metastases receive stereotactic radiosurgery
      (SRS) with the objective of improving survival and intracranial disease control.
      Brain metastases number and volume are prognostic factors used to inform patient
      selection. The aim of this study was to assess the rate of change of brain
      metastases size and number (growth kinetics) between the diagnostic and day of
      SRS magnetic resonance imaging (MRI) scans. MATERIALS AND METHODS: All patients
      treated with Gamma Knife SRS between October 2015 and April 2017 were included in
      this single-centre retrospective analysis. Brain metastases number and diameter
      were recorded at diagnosis and treatment. For patients with multiple brain
      metastases, the largest lesion was the index lesion. Distant intracranial control
      and overall survival were reported from the date of SRS. RESULTS: In total, 146
      patients received 156 episodes of SRS. The median interval between diagnostic and
      SRS MRI was 20 days (range 1-68). Interval growth in the index lesion of at least
      3 mm or the development of a new brain metastasis was noted in 60.2% of patients.
      This was associated with age less than 60 years (P = 0.001), Eastern Cooperative
      Oncology Group (ECOG) performance status 2 or above (P = 0.04), non-small cell
      lung carcinoma (NSCLC) (P = 0.03) or melanoma histologies (P = 0.05) and
      uncontrolled extracranial disease (P = 0.05). These patients were also more
      likely to develop distant intracranial recurrence (P = 0.046). Clinically
      significant growth was not associated with scan interval or differences in
      overall survival. The Kaplan-Meier estimate of probability of survival at 12
      months was 59.3% (95% confidence interval 46.7-75.2%) for all patients.
      CONCLUSION: Intracranial progression between diagnosis and day of SRS is common.
      Risk factors are uncontrolled extracranial disease, poorer performance status,
      NSCLC or melanoma histologies and age less than 60 years. These patients would
      benefit from an MRI closer to treatment to inform patient selection and target
      delineation for SRS planning.

PMID- 30279040
TI  - Editorial commentary: Pulmonary hypertension in left heart disease: Definitions,
      data sources, and the road ahead.

PMID- 30279039
TI  - Military Brain Science - How to influence future wars.
AB  - Military Brain Science is a cutting-edge innovative science that uses potential
      military application as the guidance. It was preliminarily divided into 9 aspects
      by authors: understanding the brain, protecting the brain, monitoring the brain,
      injuring the brain, interfering with the brain, repairing the brain, enhancing
      the brain, simulating the brain and arming the brain. In this review, we attempt
      to propose the concept, content and meaning of the Military Brain Science, with
      the hope to provide some enlightenment and understanding of the research area.

PMID- 30279041
TI  - Editorial commentary: Noninvasive imaging for vascular inflammation - A journey
      to the deep.

PMID- 30279042
TI  - A methodology for customizing clinical tests for esophageal cancer based on
      patient preferences.
AB  - BACKGROUND: Clinical tests for diagnosis of any disease may be expensive,
      uncomfortable, time consuming and can have side effects e.g. barium swallow test
      for esophageal cancer. Although we can predict non-existence of esophageal cancer
      with near 100% certainty just using demographics, lifestyle, medical history
      information, and a few basic clinical tests but our objective is to devise a
      general methodology for customizing tests with user preferences to avoid
      expensive or uncomfortable tests. METHOD: We propose to use classifiers trained
      from electronic medical records (EMR) for selection of tests. The key idea is to
      design classifiers with 100% false normal rates, possibly at the cost of higher
      false abnormal. We find kernel logistic regression to be most suitable for the
      task. We propose an algorithm for finding the best probability threshold for
      kernel LR, based on test set accuracy tuning with help of a validation data set.
      Using the proposed algorithm, we describe schemes for selecting tests, which
      appear as features in the automatic classification algorithm, using preferences
      on costs and discomfort of the users i.e the proposed method is able to detect
      almost all true patients in the population even with user preferred clinical
      tests. RESULT: We test our methodology with EMRs collected for more than 3000
      patients, as a part of project carried out by a reputed hospital in Mumbai,
      India. We found that kernel SVM and kernel LR with a polynomial kernel of degree
      3, yields an accuracy of 99.18% and sensitivity 100% using only demographic,
      lifestyle, patient history, and basic clinical tests. We demonstrate our test
      selection algorithm using two case studies, one using cost of clinical tests, and
      other using "discomfort" values for clinical tests. We compute the test sets
      corresponding to the lowest false abnormals for each criterion described above,
      using exhaustive enumeration of 12 and 15 clinical tests respectively. The sets
      turn out to be different, substantiating our claim that one can customize test
      sets based on user preferences.

PMID- 30279043
TI  - Longitudinal trend of global artemisinin research in chemistry subject areas
      (1983-2017).
AB  - Artemisinin, the initial and main drug for malaria prevention and treatment
      internationally, was first extracted from the plant Artemisia annua L. by Chinese
      scientists in 1972. Research on artemisinin in chemistry subject areas shows a
      rapid growth since the 1980s. To evaluate the evolutionary trends and draw the
      knowledge map of artemisinin research, 1316 relevant publications are analysed
      based on bibliometrics. The global research status, emerging trends and future
      directions are also visualised and discussed. Furthermore, a historical overview
      of chemical synthesis on artemisinin is illustrated via timeline in terms of
      industrialisation. Overall, this study provides a novel method to visualise
      further information about artemisinin research and a comprehensive perspective to
      understand the longitudinal trend over the last 30 years.

PMID- 30279044
TI  - Synthesis and evaluation of 2-substituted 4(3H)-quinazolinone thioether
      derivatives as monoamine oxidase inhibitors.
AB  - In the present study, a series of fourteen 2-mercapto-4(3H)-quinazolinone
      derivatives was synthesised and evaluated as potential inhibitors of the human
      monoamine oxidase (MAO) enzymes. Quinazolinone is the oxidised form of
      quinazoline, and although this class has not yet been extensively explored as MAO
      inhibitors, it has been shown to possess a wide variety of biological activities.
      Among the quinazolinone derivatives investigated, seven compounds (IC50 < 1 uM)
      proved to be potent and specific MAO-B inhibitors, with the most potent
      inhibitor, 2-[(3-iodobenzyl)thio]quinazolin-4(3H)-one, exhibiting an IC50 value
      of 0.142 MUM. Further investigation showed that this inhibitor is a reversible
      and competitive inhibitor of MAO-B with a Ki value of 0.068 uM. None of the test
      compounds were MAO-A inhibitors. Analysis of the structure-activity relationships
      (SARs) for MAO-B inhibition shows that substitution on the C2 position of
      quinazolinone with a benzylthio moiety bearing a Cl, Br or I on the meta position
      yields the most potent inhibitors of the series. In contrast, substitution with
      the unsubstituted benzylthio moiety (IC50 = 3.03 uM) resulted in significantly
      weaker inhibition activity towards MAO-B. This study suggests that quinazolinones
      are promising leads for the development of selective MAO-B inhibitors which may
      be used for the treatment of neurodegenerative disorders such as Parkinson's
      disease.

PMID- 30279045
TI  - Sensitization to Api m 1, Api m 2, and Api m 4 in Japanese beekeepers who had
      experienced systemic reactions to honeybee stings.

PMID- 30279046
TI  - Treatment outcomes for unresectable intrahepatic cholangiocarcinoma: Nationwide,
      population-based, cohort study based on propensity score matching with the
      Mahalanobis metric.
AB  - PURPOSE: No prospective randomized trials have been conducted to date to evaluate
      the efficacy of palliation of pain or jaundice without treatment, definitive
      concurrent chemoradiotherapy (CCRT), sequential chemotherapy and radiotherapy
      (CTRT), or chemotherapy (CT) alone for treating unresectable intrahepatic
      cholangiocarcinoma (ICC). We designed a nationwide, population-based, cohort
      study to determine the effects of different treatments on patients with
      unresectable ICC using propensity score matching (PSM) with the Mahalanobis
      metric. PATIENTS AND METHODS: We classified patients with unresectable ICC from
      the Taiwan Cancer Registry database into the following 4 treatment groups: group
      1, definitive CCRT; group 2, sequential CTRT; group 3, no treatment (palliative
      therapy for relief of pain, pruritus, or jaundice); and group 4, CT alone.
      Confounding factors among the 4 treatment groups were minimized through
      propensity score matching (PSM). RESULTS: After PSM, the final cohort consisted
      of 844 patients (211 patients in each of the 4 groups). In both univariable and
      multivariable Cox regression analyses, adjusted hazard ratios (aHRs; 95%
      confidence interval [CI]) derived for groups 1 and 2 compared with group 4 were
      0.65 (0.59-0.71) and 0.95 (0.83-1.48), respectively. Furthermore, an aHR (95% CI)
      of 2.25 (1.89-2.67) was derived for significant independent prognostic risk
      factors for poor overall survival for group 3 compared with group 4. CONCLUSIONS:
      Definitive CCRT is the optimal therapy for patients with unresectable ICC without
      distant metastasis.

PMID- 30279048
TI  - In reply to Keenan et al. Anatomic principles as the basis of target volume
      definition.

PMID- 30279047
TI  - A cross sectional study in cognitive and neurobehavioral impairment in long-term
      nasopharyngeal cancer survivors treated with intensity-modulated radiotherapy.
AB  - PURPOSE/OBJECTIVES: To determine neurocognitive and neurobehavioral impairment in
      long-term nasopharyngeal cancer survivors (NPC) treated with intensity-modulated
      radiotherapy (IMRT). MATERIALS/METHODS: A cross-sectional cohort of NPC >=4 years
      (y) following IMRT was assessed. Objective cognitive function was measured using
      the Montreal Cognitive Assessment (MoCA) and patient-reported memory was assessed
      with the MDASI-HN problems remembering item. Patient and family ratings of
      patients' neurobehavioral symptoms of apathy, disinhibition and executive
      dysfunction were assessed with the Frontal Systems Behavior Scale (FrSBe). Other
      patient-reported symptoms (MDASI-HN), mood (HADS), and quality of life (FACT-H&N)
      were also collected. RESULTS: Among 102 participants: M:F = 66:36; median age 56y
      (32-77); median time since IMRT 7.5y (4.2-11.1). Impaired MoCA scores (<23) were
      observed in 33 (32%). Patient and family ratings of pre-illness neurobehavioral
      symptoms were in the normal range (total FrSBe T-scores 53.3 and 59.0
      respectively). In contrast, post-treatment patient and family T-scores were
      clinically impaired (64.7, 71.3 respectively), with apathy, disinhibition and
      executive dysfunction post-treatment ratings all significantly worse than pre
      treatment (p < 0.001). Prevalence of clinically significant post-treatment
      disturbance was high by patient and family ratings (48%/66% apathy, 35%/53%
      disinhibition, 39%/56% executive dysfunction). Post-treatment neurobehavioral
      symptoms strongly correlated with lower quality of life (r = -0.62) and higher
      anxiety (r = 0.62) and depression scores (r = 0.67, all p < 0.001). Total MoCA
      scores did not correlate with RT dose. However, greater declines in apathy,
      disinhibition and executive dysfunction were associated with receiving >75 Gy to
      temporal lobes. CONCLUSION: NPC treated with IMRT had moderate to high rates of
      neurocognitive impairment and clinically significant apathy, disinhibition, and
      executive dysfunction.

PMID- 30279050
TI  - Age as a prognostic factor in relation to surgical evacuation of spontaneous
      supratentorial intracerebral haemorrhage.
AB  - AIM AND CLINICAL RATIONALE FOR THE STUDY: Spontaneous intracerebral haemorrhage
      (sICH) is an acute life-threatening injury and constitutes 10-15% of first-ever
      stroke cases. The Surgical Trials in Intracerebral Haematoma studies (STICH and
      STICH II) represent the two foremost studies in the field, however, with arguable
      shortcomings. To find more accurate criteria, we aimed to correlate the
      preoperative neurological and neuroimaging findings with the clinical outcome of
      operated patients. MATERIALS AND METHODS: In this retrospective study, sICH
      patients were recruited from the Central Denmark Region from 2010 to 2016. We
      evaluated the patients' medical records regarding preoperative Glasgow Coma Scale
      (GCS) 6 months and one year after surgery, focal neurological defects,
      thrombolytic treatment, pupil status, and haemorrhage localization visualized by
      neuroimaging. The patients' clinical outcome was assessed using the Glasgow
      Outcome Scale (GOS). RESULTS: Based on logistic multiple linear analysis, age,
      basal ganglia haemorrhage and mass effect had significant effect on the mortality
      rate. Besides, age, basal ganglia haemorrhage, intra ventricular haemorrhage and
      pupil difference had significant correlation with good outcome (GOS>3).
      CONCLUSIONS AND CLINICAL IMPLICATIONS: Neurosurgical treatment of the sICH
      patients is indicated only if age and potentially improved morbidity is carefully
      evaluated considering the STICH and this study; otherwise, we will just increase
      the health care burden with a number of extremely care-dependent patients.

PMID- 30279049
TI  - Quantitative radiomics: Validating image textural features for oncological PET in
      lung cancer.
AB  - BACKGROUND AND PURPOSE: Radiomics textural features derived from PET imaging are
      of broad and current interest due to recent evidence of their prognostic value
      during cancer management. An inherent assumption is the link between these
      imaging features and the underlying tumoral phenotypic spatial heterogeneity. The
      purpose of this work was to validate this assumption for tumors within the lung
      through a comparison of image based textural features and the ground truth
      activity distribution from which the images were created. A second purpose was to
      assess the level at which PET imaging introduces spatial texture not present in
      the associated ground truth activity distribution. MATERIALS AND METHODS: 25 lung
      lesions were created using an anthropomorphic phantom. Ten of the lesions had a
      spherical shape with a uniform activity distribution. The remaining 15 had an
      irregular shape with a heterogeneous activity distribution. PET images were
      created for each lesion using Monte Carlo simulation. 79 textural features
      related to the gray-level intensity histograms, co-occurrence matrices,
      neighborhood difference matrices, run length, and size zone matrices were derived
      from both the simulated PET images and ground truth activity maps. A comparison
      was made between the two datasets using statistical analysis. RESULTS: For
      homogenous lesions, features extracted from the PET images were largely
      irrelevant to the underlying uniform activity distribution. Additionally, the
      majority of these features assumed substantial values implying that an extensive
      amount of spatial texture had been introduced into the final imaging data. For
      heterogeneous lesions, complex trends were observed in the deviation between
      features extracted from PET images and those extracted from the ground truth
      activity maps. Moreover, the extent of both the deviation and the associated
      dynamic range was seen to be greatly feature-dependent. CONCLUSION: The use of
      image based textural features as a surrogate for tumoral phenotypic spatial
      heterogeneity could not be clearly validated. The association between the two is
      complex and a significant amount of uncertainty exist due to the introduction of
      incidental texture during image acquisition and reconstruction.

PMID- 30279051
TI  - TRIO gene segregation in a family with cerebellar ataxia.
AB  - AIM OF THE STUDY: To report a family with a novel TRIO gene mutation associated
      with phenotype of cerebellar ataxia. MATERIALS AND METHODS: Seven family members
      of Caribbean descent were recruited through our ataxia research protocol; of the
      family members, the mother and all 3 children were found to be affected with
      severe young-onset and rapidly progressive truncal and appendicular ataxia
      leading to early disability. Array comparative genomic hybridization,
      mitochondrial DNA analysis, and whole-exome sequencing were performed on 3 of the
      family members (mother and 2 daughters). RESULTS: While the maternal grandmother,
      great uncle and great aunt were unaffected, the mother and 3 children displayed
      cognitive dysfunction, severe ataxia, spasticity, and speech disturbances. Age of
      onset ranged between 3 and 17 years, with average current disease duration of 21
      years. Whole-exome sequencing showed a variant p.A1214V in exon 22 of the TRIO
      gene in 3 of the family members. Array comparative genomic hybridization and
      mitochondrial DNA analysis were normal. The same variant was later discovered in
      all but one family member. CONCLUSIONS AND CLINICAL IMPLICATIONS: The TRIO
      p.A1214V variant is associated with cerebellar ataxia in the studied family; it
      was present in all affected and unaffected family members. Phenotype is severe
      and broad. Anticipation seems to be present (based on 2 affected generations). It
      is warranted to screen additional familial early-onset and rapidly progressive
      ataxia cases for this genotype. TRIO gene mutations may well represent a novel
      spinocerebellar ataxia subtype.

PMID- 30279052
TI  - Spinal anesthesia performed for cesarean delivery after external ventricular
      drain placement in a parturient with symptomatology from an intracranial mass.
AB  - We describe a case in which spinal anesthesia was undertaken in a pregnant
      patient with a space-occupying tumor and significant symptomatology. The
      collaborative efforts of all medical disciplines involved and the willingness of
      the neurosurgeon to discuss and help determine the safety of neuraxial
      anesthesia, culminated in placing an external ventricular drain to help monitor
      and manage intracranial pressure, so that we could proceed with spinal anesthesia
      and more easily monitor neurologic status.

PMID- 30279053
TI  - Rotational thromboelastometry (ROTEM(r))-guided diagnosis and management of
      amniotic fluid embolism.
AB  - Amniotic fluid embolism is a rare but often catastrophic emergency. The non
      specific clinical features and lack of diagnostic tests make it a diagnosis of
      exclusion. Point-of-care visco-elastometric testing is being increasingly used
      during obstetric haemorrhage. We present a case of amniotic fluid embolism,
      diagnosed and managed using rotational thromboelastography. During a precipitous
      labour, a 21-year-old multiparous woman became pale, distressed and
      disorientated. The fetus was delivered using forceps. Simultaneously maternal
      cardiac arrest occurred and advanced life support was commenced. As there was no
      obvious bleeding, pulmonary embolism was considered the most likely diagnosis and
      preparation was made to thrombolyse. During resuscitation, rotational
      thromboelastometry demonstrated haemostatic failure, supporting a diagnosis of
      amniotic fluid embolism. This reversed the decision to thrombolyse and focused
      the team on resuscitation and management of coagulopathy. Targeted blood products
      were given using a local protocol specific to obstetric bleeding. Return of
      cardiac output was achieved. The total measured blood loss was more than 3.6 L
      and transfusion was guided by point-of-care tests. Transfused blood products were
      six units of packed red blood cells, one pool of platelets, 12 units of fresh
      frozen plasma and 14 g of fibrinogen concentrate. This case demonstrates amniotic
      fluid embolism with haemostatic failure, without initial revealed blood loss. The
      high mortality of amniotic fluid embolism necessitates rapid diagnosis and
      aggressive management. Laboratory tests in this context are impractical in
      informing clinical decisions, showing the value of point-of-care testing in
      facilitating team work and timely administration of targeted blood products.

PMID- 30279055
TI  - Corrigendum to "Guidelines for preparing color figures for everyone including the
      colorblind" [Pharmacol. Res. 119 (2017) 240-241].

PMID- 30279054
TI  - Women Veterans' Experiences with Department of Veterans Affairs Maternity Care:
      Current Successes and Targets for Improvement.
AB  - INTRODUCTION: Little is known about women veterans' experiences accessing and
      using Department of Veterans Affairs (VA) maternity care, which is nearly all
      purchased from non-VA providers. OBJECTIVE: To understand women veterans'
      experiences, preferences, and challenges using VA maternity care. METHODS: We
      conducted 27 semistructured interviews with women veterans who used VA maternity
      care during fiscal year 2016. To capture a wide variety of experiences, we
      randomly sampled veterans from urban and rural VA facilities with higher and
      lower volumes of VA paid deliveries. All interviews were recorded and transcribed
      verbatim. Transcripts were analyzed using inductive and deductive content
      analysis. RESULTS: Themes included experiences initiating prenatal care,
      obtaining prenatal and lactation classes, the role of maternity care
      coordinators, mental health care, and satisfaction with care. Women described
      challenges obtaining authorization for care and establishing care with non-VA
      providers. First-time mothers appreciated the availability of prenatal and
      lactation classes. VA maternity care coordinators helped women veterans to
      navigate the challenges related to VA maternity care, ranging from finding non-VA
      providers to billing. The majority of participants were engaged with mental
      health care before pregnancy and continued this care during pregnancy. Women's
      satisfaction with VA maternity care was impacted by access to supportive,
      knowledgeable providers; care coordinators; woman-centered labor and delivery
      experiences; and billing issues. CONCLUSIONS: Our findings provide a portrait of
      the current state of VA maternity care from the perspectives of women veterans
      and highlight areas, such as care coordination and woman-centered models for
      labor and delivery, that can improve satisfaction with care.

PMID- 30279056
TI  - Real-time fish stress visualization came true:A novel multi-stage color-switching
      wireless biosensor system.
AB  - An optical communication type biosensor system has been developed which can
      measure blood glucose concentration, which is a stress indicator of fish, in real
      time while fish swimming freely. However, this system is hard to make instant
      acknowledgment of fish stress level which has to contain an unavoidable delay in
      the judgment. In this research, we aimed to develop a novel stress visualization
      system which can quickly judge the levels for fish stress response instantly
      based on a color changeable LED while another LED was designed to send data. The
      present system is based on the principle of converting the output current value
      measured by the glucose biosensor corresponding to the stress response into a
      voltage value. Then, the color and stress switching points of the LED (Red,
      Yellow, Green) were decided based on the voltage value gained from the biosensor
      which mentioned above. Furthermore, we attempted to use our biosensor system to
      make real-time monitoring of fish stress in vivo. As results, the proposed sensor
      can make real-time measurement of glucose and shows a great response to those of
      actual fish sample in the range from 35.36 to 300 mg dl-1 (R = 0.9899). When the
      glucose concentration in the collected sample was switched to the concentration
      pre-sett, it was successful to switch the LED color according to the gained
      voltage value both in vitro and in vivo. Furthermore, when monitoring the stress
      responses of the fish in vivo, color switching corresponding to the sensor output
      current value was observed successfully.

PMID- 30279057
TI  - Fully printed one-step biosensing device using graphene/AuNPs composite.
AB  - Driven by the growing need of simple, cost efficient and flexible sensing
      systems, we have designed here a fully printed Reduced Graphene Oxide (rGO) based
      impedimetric sensor for one step sensing of DNA. The DNA sensor was fabricated by
      stamping of layered rGO and rGO/gold nanoparticles/single stranded DNA
      (rGO/AuNPs/ssDNA) composites over PET substrates using wax-printing technique.
      rGO works as an excellent working electrode, while the AuNPs create a suitable
      environment for ssDNA immobilization. Counter and reference electrodes were
      previously screen-printed on the plastic substrate, making thus a compact and
      highly integrated sensing platform. The change in electron transfer resistance
      after hybridization with a target ssDNA specific of Coxsackie B3 virus was
      monitored using electrochemical impedance spectroscopy (EIS), finding a linear
      response in the range of concentrations 0.01-20 uM. The novel, simple and
      straightforward one-step printing process for fabrication of a biosensing device
      developed keeps in mind the growing need of large scale device manufacturing. The
      successful proof-of-concept for the detection of DNA hybridization can be
      extended to other affinity biosensors, taking advantage of the integration of the
      bioreceptor on the sensor surface. Such ready-to-use biosensor would lead to a
      one-step electrochemical detection.

PMID- 30279058
TI  - Clinical Outcome of Ischemic Stroke in Old Patients Versus Oldest-Old.
AB  - BACKGROUND: It is unclear whether very old patients benefit from stroke unit. The
      aim of our work was to compare the clinical outcome of patients with ischemic
      stroke aged either 70 or 80 (G 1) versus oldest-old greater than or equal to 81
      years (G 2). METHODS: Of 1187 patients admitted with stroke during 5 years in our
      stroke unit, we included 252 patients with independent functional status
      (modified Rankin scale, [mRS] <= 2) before the stroke. All patients underwent
      clinical examination, blood test, electrocardiography, brain imaging, and
      cerebrovascular ultrasound. Clinical outcome was assessed with the mRS and
      National Institutes of Health Stroke Scale (NIHSS) at discharge. We considered
      favorable outcome mRS 0-2 at discharge. RESULTS: Of 252 patients included, 55%
      were male, 150 (59.5%) patients belonged to G1 and 102 (40.5%) G2. We detected a
      significant increase of atrial fibrillation, bronchoaspiration, mortality, higher
      NIHSS at admission, and worse functional status at discharge in G2. No
      significant differences in other demographic, vascular risk factors, hospital
      stay, NIHSS at discharge or subtype of stroke were found. NIHSS at discharge was
      the only independent predictor of good functional status (odds ratio 0.4; 95%
      confidence interval, 0.3-0.6; P < .001). CONCLUSIONS: Oldest-old patients showed
      similar NIHSS at discharge than younger patients despite having higher
      neurological severity at admission. Our results support the hypothesis that
      oldest-old patients have good recovery potential, and should not be excluded from
      the stroke unit. The worse functional status detected at discharge in these
      patients could be attributed to others factors and not to neurological severity.

PMID- 30279059
TI  - Fever of Unknown Origin due to a Mycotic Abdominal Aortic Aneurysm First
      Diagnosed with Bone 99mTc Scintigraphy.

PMID- 30279060
TI  - Defining delirium in idiopathic Parkinson's disease: A systematic review.
AB  - BACKGROUND: Parkinson's disease patients may be at increased risk of delirium and
      developing adverse outcomes, such as cognitive decline and increased mortality.
      Delirium is an acute state of confusion that has overlapping symptoms with
      Parkinson's dementia, making it difficult to identify. This study aimed to
      determine the diagnostic criteria, prevalence, management strategies and outcomes
      of delirium in Parkinson's through a systematic review of the literature.
      METHODS: Seven databases were used to identify all articles published before
      February 2017 comprising two key terms: "Parkinson's Disease" and "delirium".
      Data were extracted from studies meeting predefined inclusion criteria. RESULTS:
      Twenty articles were identified. Delirium prevalence in Parkinson's ranged from
      0.3 to 60% depending on setting; a diagnosis of Parkinson's was associated with
      an increased risk of developing delirium. Delirium was identified/diagnosed using
      seven different criteria. Delirium may be associated with an increased length of
      hospital stay and worsening motor symptoms. We did not identify any studies
      examining the management of delirium in Parkinson's. DISCUSSION: This review
      highlights the paucity of well-designed, appropriately powered studies
      investigating delirium in Parkinson's. The results suggest that delirium is a
      significant issue in people with Parkinson's and that having delirium may be a
      risk factor for adverse outcomes, particularly in inpatient settings. Further
      prospective research is needed to accurately determine the prevalence of delirium
      in Parkinson's, its management strategies and outcomes, and to evaluate
      diagnostic criteria to differentiate between the overlapping symptoms of
      Parkinson's and delirium.

PMID- 30279061
TI  - Alpha-synuclein staining in non-neural structures of the gastrointestinal tract
      is non-specific in Parkinson disease.

PMID- 30279062
TI  - Prediction of acute kidney injury after radical cystectomy and urinary diversion.

PMID- 30279063
TI  - Necrotizing enterocolitis.

PMID- 30279064
TI  - Expiratory Central Airway Collapse in Adults: Anesthetic Implications (Part 1).
AB  - Expiratory central airway collapse (ECAC) is a general term that incorporates
      tracheobronchomalacia (TBM) and excessive dynamic airway collapse (EDAC). TBM and
      EDAC are progressive, degenerative disorders of the tracheobronchial tree,
      causing airway collapse. Induction of general anesthesia can trigger
      intraoperative airway collapse in patients with these conditions. This crisis
      presents as the sudden inability to ventilate, which can lead to life-threatening
      hypoxemia and hypercapnia. This article reviews the definition, pathophysiology,
      diagnosis, and anesthetic implications of ECAC.

PMID- 30279065
TI  - Comparison of Coagulation Parameters in Arterial and Venous Blood in Cardiac
      Surgery Measured Using the Quantra System.
AB  - OBJECTIVE: Perioperative coagulation testing often is performed with arterial
      samples even though device reference ranges typically are established in venous
      samples. Although limited studies exist comparing coagulation parameters across
      sampling sites, viscoelastic testing devices have demonstrated some differences.
      The objective of this study was to compare coagulation parameters determined
      using the Quantra System for venous and arterial samples. DESIGN: Prospective,
      observational study. SETTING: Tertiary care university hospital. PARTICIPANTS:
      The study comprised 30 adult patients undergoing cardiac surgery. INTERVENTIONS:
      Paired arterial and venous samples were obtained at 2 of the following time
      points: baseline, during bypass, or after protamine reversal of heparin. Quantra
      measurements included Clot Time (CT), Heparinase Clot Time (CTH), Clot Time Ratio
      (CTR), Clot Stiffness (CS), and Fibrinogen (FCS) and Platelet (PCS) Contributions
      to clot stiffness. MEASUREMENTS AND MAIN RESULTS: The relationship and agreement
      between matched data pairs were established and statistical analysis was
      performed via paired t tests. CTR, CS, FCS, and PCS were unaffected by the
      sampling site, whereas CT and CTH demonstrated statistically significant
      differences between arterial and venous samples (p < 0.001). Arterial clot times
      were prolonged relative to the venous ones with a mean percent error of 14.2 %
      and 11.9 %, respectively. These results are in general agreement with those
      reported for other viscoelastic testing devices. CONCLUSIONS: This study
      demonstrates that Quantra clot stiffness-based parameters (CS, FCS, PCS) are
      unaffected by sampling site, whereas the clot time parameters (CT and CTH) show
      good correlation in the presence of a bias. CTR, a ratio of CT and CTH, also is
      unaffected.

PMID- 30279066
TI  - Expiratory Central Airway Collapse in Adults: Corrective Treatment (Part 2).
AB  - Corrective treatment of expiratory central airway collapse (ECAC) consists of
      placement of airway stents or tracheobronchoplasty (TBP). The indication for
      corrective treatment is severe central airway collapse (>90 %), and severe
      symptoms that cause decline in quality of life. Patients are selected to undergo
      a trial of tracheal "Y" stent placement. If symptoms improve (positive trial)
      they undergo a TBP, provided they are good surgical candidates. Patients who are
      considered poor surgical candidates because of the severity of comorbidities can
      be offered permanent stenting to palliate symptoms. The anesthetic management of
      airway stent placement and TBP is complex. This article reviews the medical
      management and corrective treatment of ECAC, anesthetic management of airway
      stent placement, and considerations during TBP.

PMID- 30279067
TI  - Mitral Valve Replacement in a Patient With Systemic Mastocytosis.

PMID- 30279068
TI  - Water, Wine and the Sacred, an Anthropological View of Substances Altered by
      Intentioned Awareness, Including Objective and Aesthetic effects.
AB  - This paper discusses the ancient anthropological linkage of water and wine with
      sacred rituals after these substances have been the focus of nonlocal
      perturbation. The paper reports the changes produced can be both physical, as
      well as a subjective aesthetic reaction arising when individuals have a sensorial
      interaction with such treated substances. In making this argument the paper
      presents and discusses research done by others, as well as the author including
      reporting the results of a 12 part series of experiments in which groups of seven
      people tasted wine from one 750 ml bottle that had been decanted into two
      identical 375 ml carafes. The histories of the carafes were the same except that
      one, before the tasting, had been the focus of intentioned awareness by
      meditators, while the other was a control. Twelve sessions were conducted, 11
      resulted in a majority preferring the treated wine, and one resulted in a tie.
      Using an exact binomial test, the p-value is (0.5)11=12048=0.00049. Therefore,
      with 95% confidence we can say that the probability that a majority would prefer
      the treated wine is at least 0.76. The paper in its conclusion discusses the
      implications of the totality of this research.

PMID- 30279069
TI  - Miracle Healings.

PMID- 30279070
TI  - Food Sources for Homeless Youth: An Evaluation of Food Availability at a Homeless
      Youth Drop-In Center.
AB  - OBJECTIVE: We utilized a validated food inventory questionnaire to assess the
      types and quality of food available at a homeless youth drop-in center. METHODS:
      Scores for 13 food categories were computed; higher scores indicated a greater
      availability of foods found in that category. A summative score was computed to
      assess the presence of obesogenic foods. RESULTS: Dry cereal, vegetables, and
      meat, were the most available foods; 83.3%, 60.9%, and 56.3% of food items in
      each category, respectively, were available. The food categories with least
      available items included candy and dairy: 26.6% and 25.4% of items in those
      categories, respectively. Mean obesogenic food availability score was 31 +/- 4.2
      (range 23-34), out of a possible score of 71. CONCLUSIONS AND IMPLICATIONS: It is
      possible for a drop-in center to provide healthful foods to homeless youth.
      Further studies examining the extent to which drop-in centers contribute to the
      homeless youth food environment are warranted.

PMID- 30279071
TI  - Protein Language: Post-Translational Modifications Talking to Each Other.
AB  - Post-translational modifications (PTMs) are at the heart of many cellular
      signaling events. Apart from a single regulatory PTM, there are also PTMs that
      function in orchestrated manners. Such PTM crosstalk usually serves as a fine
      tuning mechanism to adjust cellular responses to the slightest changes in the
      environment. While PTM crosstalk has been studied in depth in various species; in
      plants, this field is just emerging. In this review, we discuss recent studies on
      crosstalk between three of the most common protein PTMs in plant cells, being
      phosphorylation, ubiquitination, and sumoylation, and we highlight the diverse
      underlying mechanisms as well as signaling outputs of such crosstalk.

PMID- 30279072
TI  - Geminivirus C4: Interplaying with Receptor-like Kinases.
AB  - Geminivirus infection results in systemic symptoms in plants, but the mechanism
      by which the virus affects cell-to-cell signalling involved in development and
      resistance remains unclear. Based on recent evidence, we suggest a potential
      mechanism that geminivirus C4 proteins interfere with intercellular signals by
      interacting with receptor-like kinases on the plasma membrane.

PMID- 30279073
TI  - The evaluation of forensic characteristics and the phylogenetic analysis of the
      Ong Be language-speaking population based on Y-STR.
AB  - The Ong Be language, an important branch of the Tai-Kadai language family, is one
      of the most distinctive languages on Hainan Island. Ong Be language speakers, who
      have lived in the Lingao district of Hainan Island for generations, were
      classified as Han Chinese in the early days of the establishment of the People's
      Republic of China but have distinct differences from the Han Chinese in language,
      lifestyle, customs and values and particularly in appearances and features.
      Currently, Y-chromosomal short tandem repeat (STR) haplotypes have been widely
      used in genetic applications, such as human forensics, historical investigations
      and genealogical research. In this study, 487 unrelated male individuals residing
      in the Lingao district volunteered, and their Y-STR haplotypes were investigated
      using the Yfiler and Yfiler Plus with 17 and 27 Y-STR loci, respectively.
      Furthermore, we combined our population data on the Lingao people with existing
      datasets from Asian nations (East, South and Southeast Asia) to explore the
      genetic variance and relationships with Han Chinese from different administrative
      regions in Northern and Southern China and Chinese ethnic minorities officially
      recognized by the PRC. Population comparisons demonstrated that the Lingao people
      had distant relationships with Asian nations at the national level and had
      relatively close genetic and linguistic relationships with Hainan Li and Guizhou
      Gelao, both of whom belong to the Tai-Kadai language family. The present results
      increase our understanding of the genetic relationships between the Lingao people
      and other groups, and further research in genetics and other areas is still
      needed to trace the origin of the Lingao people.

PMID- 30279074
TI  - Relationship between somatostatin and interleukin-6: A cross-sectional study in
      patients with acute pancreatitis.
AB  - OBJECTIVES: The aim of the analysis is to determine dynamic changes in
      somatostatin (SS) and interleukin-6 (IL-6) concentrations during in acute
      pancreatitis (AP). METHODS: The influence of tobacco smoking on IL-6 and SS
      levels in the serum of non-smoking (n = 10) and smoking (n = 27) patients with
      diagnosed AP and control group: non-smoking (n = 44), smoking (n = 42) and
      passive smoking (n = 29) healthy persons was proved. The concentration of IL-6
      and SS was determined by means of ELISA. Differences between the groups analyzed
      were tested using the U Mann Whitney test. The Spearman rank correlation analysis
      was used to evaluate the correlations. RESULTS: The concentrations of IL-6 and SS
      were significantly higher in smoking patients with AP and healthy persons when
      compared with non-smoking population on every day (1 day: p = 0.0002, p = 0.015;
      3 day: p = 0.005, p = 0.001 and 7 day: p = 0.025, p = 0.038). Dynamic changes in
      concentrations of IL-6 and SS in the serum of patients with AP were demonstrated
      in the ensuing days of the disease. In case of non-smoking and smoking patients,
      significant positive correlations between IL-6 and SS was observed. CONCLUSIONS:
      These findings suggest that some of the antiinflammatory effects of SS against
      acute pancreatitis may be mediated by reducing the local proinflammatory cytokine
      secretion in the pancreas.

PMID- 30279075
TI  - Phenotyping and long-term follow up of patients with hyper IgE syndrome.
AB  - INTRODUCTION AND OBJECTIVES: Long-term follow up of patients with hyper IgE
      syndrome (HIES), as a primary immunodeficiency disorder, has been poorly
      investigated. This study describes common clinical and immunological features of
      patients with HIES in the last 10 years in Shiraz University of Medical Sciences,
      Shiraz, Iran. METHODS AND PATIENTS: In this cross-sectional study, the symptoms
      and medical records of 18 patients, who were diagnosed with HIES, were observed.
      Genetic and immunologic study was also performed. RESULTS: Eighteen patients with
      the mean age of 13 years old were investigated. Ten patients were detected to
      have mutations in DOCK8 gene and autosomal recessive HIES (AR-HIES); and four
      patients were found with STAT3 mutation and autosomal dominant HIES (AD-HIES).
      So, 14 patients with known genetic results were considered for further data
      analysis. Food allergy, eczema, viral and skin infections were the major
      complications of AR-HIES patients. The major clinical complications of AD-HIES
      patients were pneumonia, skin infections and eczema. Food allergy and viral
      infection were significantly higher in DOCK8 deficient patients. The most common
      causes of hospitalization in both AR-HIES and AD-HIES patients were pneumonia,
      skin infections and sepsis. The most common cause of death was found to be
      sepsis. CONCLUSIONS: AD-HIES and AR-HIES cannot be differentiated only based on
      the clinical presentations. Genetic features are also necessary for better
      diagnosis. This study, summarizing the clinical, immunological and genetic
      information of the patients with AD-HIES and AR-HIES, may open a way for better
      diagnosis and management of HIES.

PMID- 30279076
TI  - Helge Karch-The EHEC hunter.

PMID- 30279077
TI  - Greater curvature as a gastric pouch for sleeve gastrectomy: a novel bariatric
      procedure. Feasibility study in a canine model.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has serious complications, such
      as leaks, reflux, stenosis, and kinks, which are also consequences of
      shortcomings in the LSG technique. OBJECTIVES: We evaluated the feasibility and
      weight loss of a novel bariatric procedure, using the greater curvature as the
      gastric pouch for sleeve gastrectomy (SG) in dogs. SETTING: Animal house in
      Faculty of Medicine, Cairo University. METHODS: Five 20- to 25-kg stray mongrel
      male dogs were subjected to open SG using the greater curve as the gastric pouch
      (GCSG group). The weight was monitored at day of surgery and at postoperative
      weeks 2, 4, 6, and 8; weight progression was compared with a sham and a standard
      SG group. By the end of the follow-up period autopsy was done. RESULTS: The mean
      operative time in GCSG group was 39.6 +/- 3.97 minutes. At the end of the study,
      dogs in the sham group had gained 8% of their preoperative weight, while the GCSG
      and standard SG groups lost 24.7% and 25% of their preoperative weight,
      respectively. At autopsy, the gastric sleeve in the GCSG group showed excellent
      healing with no stenotic areas, kinks, or mucosal ulcerations. CONCLUSION:
      Greater curvature SG is technically feasible in a canine model. Larger studies
      with longer follow-up period will be needed to assess weight progression and
      resolution of the metabolic co-morbidities.

PMID- 30279078
TI  - Comment on: "Postoperative Outcomes based on Patient Participation in a Pre
      surgery Education and Weight Management Program".

PMID- 30279079
TI  - Comment on: postoperative outcomes based on patient participation in a presurgery
      education and weight management program.

PMID- 30279080
TI  - The meaning of anxiety in patients with PNES.

PMID- 30279081
TI  - Transient extreme spindles in a young child with anti-NMDAR encephalitis: A case
      report.
AB  - Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a type of immune
      mediated encephalitis, which is a new category of treatment-responsive
      paraneoplastic encephalitis. In patients with this disease,
      electroencephalography (EEG) shows non-specific findings, but recently, a unique
      EEG pattern, named the extreme delta brush, was detected in 40% of adult patients
      and was suggested to be specific to this type of encephalitis. Here, we describe
      a two-year-old boy with anti-NMDAR encephalitis, who presented with speech arrest
      and disturbances of gait and cognition several weeks after developing febrile
      convulsions. In the early stages of the disease, EEG showed 14-16 Hz, continuous,
      fast waves characterized by a high amplitude (200-500 AuV), very diffuse
      spreading, and a sharp morphology, during light sleep only, which was compatible
      with extreme spindles. As the patient's symptoms worsened, this finding was
      replaced by rhythmic, diffuse, high-voltage, slow waves. Immediately after
      immunomodulatory therapies, including intravenous methylprednisolone and
      immunoglobulin, his clinical manifestations and EEG abnormalities appeared to
      improve. We propose that although the extreme spindle is a non-specific finding
      of this type of encephalitis, early EEG monitoring might be necessary to detect
      not only the extreme delta brush pattern, but also non-specific findings,
      including extreme spindles, which would aid early diagnosis and treatment.

PMID- 30279082
TI  - Laryngeal adductor reflex and future projections for brainstem monitoring. Reply
      to "A method for intraoperative recording of the laryngeal adductor reflex during
      lower brainstem surgery in children".

PMID- 30279083
TI  - Electroencephalography and brain magnetic resonance imaging in asphyxia comparing
      cooled and non-cooled infants.
AB  - OBJECTIVE: The aim was to establish any differences in the predictive value of
      EEG and MRI for outcome in infants treated and not-treated with therapeutic
      hypothermia (HT) for perinatal asphyxia. We hypothesize that they are equally
      predictive and that combining both has the highest predictive value. STUDY
      DESIGN: We retrospectively compared data of infants with hypoxic-ischemic
      encephalopathy (HIE) who received HT (n = 45) between September 2009 and December
      2013 with those of infants with HIE born between January 2004 and August 2009,
      before HT was available (NT, n = 37). All received conventional and/or amplitude
      integrated EEG during the first days and early MRI (day 4-5). Associations of
      EEG, MRI and severe neurodevelopmental outcome (death or Bayley's -2SD below
      mean), were tested with a multivariable logistic regression analysis, corrected
      for HT. RESULTS: Forty-eight hours' EEG background pattern had a PPV of 92% and a
      NPV of 81% in HT, versus 100% and 58% in NT. MRI had a PPV of 71% and a NPV of
      93% in HT, versus 82% and 75% in NT. The adjusted OR for adverse outcome was
      0.013 (95% CI 0.002-0.154, p < 0.001) for EEG background normalization within 48
      h and 32.19 (95% CI 4.84-214.25, p < 0.001) for abnormal MRI. CONCLUSION: The
      predictive value of EEG and MRI is equal in cooled and non-cooled infants with
      HIE. Our data show a higher predictive value (death and severe outcome) for EEG
      compared to MRI. In HIE, persistent abnormal EEG background pattern until 48 h,
      combined with abnormal early MRI is strongly predictive for poor
      neurodevelopment.

PMID- 30279084
TI  - Diagnosis of tuberous sclerosis complex in the fetus.
AB  - Tuberous sclerosis complex is a dominantly inherited genetic disorder of striking
      clinical variability. It is caused by mutations in either TSC1 or TSC2 gene,
      which regulate cell growth and proliferation by inhibition of mTORC1 signaling.
      TS is characterized by the development of benign tumors in many tissues and
      organs and its neurological manifestations include epilepsy, autism, cognitive
      and behavioral dysfunction, and giant cell tumors. With mechanism-based mTOR
      inhibitors therapy now available for many of its manifestations, early diagnosis
      of TSC is very important in order to offer appropriate care, long-term
      surveillance and parental counseling. Fetal ultrasound and MRI imaging techniques
      have evolved and may capture even earlier the following TSC-associated lesions:
      cardiac rhabdomyomas, subependymal nodules, cortical tubers and renal cysts.
      Often these represent an incidental finding during a routine ultrasound.
      Furthermore, in the past decades prenatal molecular diagnosis of TSC has emerged
      as an important option for families with a known affected member; however, the
      existing evidence with regards to the clinical characteristics and long-term
      outcome of babies diagnosed prenatally with TSC is yet limited and the path that
      follows early TSC detection merits further research.

PMID- 30279085
TI  - Increased cerebral microbleeds and cortical superficial siderosis in pediatric
      patients with Down syndrome.
AB  - BACKGROUND: Patients with Down syndrome carry a third copy of the amyloid
      precursor protein gene, which is localized on chromosome 21. Consequently, these
      patients are prone to develop early-onset Alzheimer disease and cerebral amyloid
      angiopathy. Post-mortem studies suggest increased amyloid deposition to be
      already detectable in children with Down syndrome. The aim of our study was to
      evaluate if amyloid-related changes in pediatric Down syndrome patients can be
      detected in vivo using MRI biomarkers of cerebral microbleeds and cortical
      superficial siderosis. MATERIALS AND METHODS: This retrospective study included
      12 patients with Down syndrome (mean age = 5.0 years) and 12 age-matched control
      subjects (mean age = 4.8 years). Frequency and location of microbleeds and
      siderosis were assessed on blood-sensitive MRI sequences in a consensus reading
      by two radiologists applying a modified Microbleed Anatomical Rating Scale.
      RESULTS: Down syndrome patients showed a significantly higher mean microbleeds
      count and likelihood of siderosis than age-matched controls. Across groups, the
      highest microbleeds count was found in lobar regions (gray and white matter of
      frontal, parietal, temporal, and occipital lobes, and the insula), while fewer
      microbleeds were located in subcortical and infratentorial regions. The number of
      microbleeds increased over time in all three Down syndrome patients with a follow
      up exam. CONCLUSION: In vivo MRI biomarkers can support the diagnosis of early
      onset cerebral amyloid angiopathy, which might already be present in pediatric
      Down syndrome patients. This might contribute to clinical decision-making and
      potentially to the development of therapeutic and prophylactic approaches, as
      cerebral amyloid angiopathy increases the risk for intracranial hemorrhage and
      may be associated with increased risk of developing Alzheimer disease.

PMID- 30279086
TI  - Effect of phacoemulsification incision size on incision repair and remodeling:
      Optical coherence tomography assessment.
AB  - PURPOSE: To characterize the effect of incision size on corneal incision repair
      and remodeling over 3 months after cataract surgery. SETTING: Department of
      Ophthalmology, Auckland District Health Board, Auckland, New Zealand. DESIGN:
      Prospective case series. METHODS: Eyes having routine cataract surgery were
      randomized to receive 2.20 mm or 2.85 mm uniplanar clear corneal incisions.
      Anterior segment optical coherence tomography of incision thickness, length,
      width, gaping, and angle and specular microscopy of endothelial cell density
      (ECD), polymegathism, and pleomorphism were completed at baseline and 1, 7, 30,
      and 90 days postoperatively. RESULTS: Each incision group comprised 50 eyes (50
      patients). Ninety-nine patients (99%) attended all assessments. The Descemet
      membrane detachment rate was greater than 50% with 2.20 mm incisions (P = .01).
      Patients with Descemet membrane detachments had increased endothelial wound
      gaping, slower visual recovery, and increased corneal thickness at the incision
      site at all visits (phi = 0.54, P < .01). The 2.20 mm group had greater
      polymegathism despite no difference in the mean phacoemulsification energy
      between groups (2.20 mm: 32.3% +/- 6.2% [SD]; 2.85 mm: 30.8% +/- 6.5%) (P = .02).
      Ninety days postoperatively, the 2.20 mm group had a lower mean ECD (2195 +/- 360
      cells/mm2) than the 2.85 mm group (2397 +/- 335 cells/mm2) (P = .01). Final
      visual acuity, gaping, and angles were not significantly different between the
      groups. CONCLUSIONS: The 2.20 mm wide corneal incisions were more prone to trauma
      than 2.85 mm incisions during routine cataract surgery. Corneal incisions with
      signs of trauma were associated with prolonged visual recovery and slower healing
      postoperatively.

PMID- 30279087
TI  - Serial intraocular lens opacifications of different designs from the same
      manufacturer: Clinical and light microscopic results of 71 explant cases.
AB  - PURPOSE: To report clinical findings and light microscopic results of 71
      opacified hydrophilic acrylic intraocular lenses (IOLs). SETTING: Vivantes
      Klinikum Neukoelln, Ophthalmology Department, Berlin, Germany. DESIGN:
      Retrospective case series. METHODS: Sixty-three patients (71 eyes) were referred
      to the clinic because of vision-impairing IOL opacification between December 2012
      and September 2016 after routine cataract surgery elsewhere. The explanted IOLs
      were analyzed with light microscopy at the John A. Moran Eye Center (University
      of Utah, Salt Lake City, Utah, USA). Medical records were reviewed for visual
      acuity, comorbidities, and complications. Clinical follow up was 6 months.
      RESULTS: Seventy-one opacified 1-piece or 3-piece hydrophilic acrylic IOLs
      (Lentis) of different designs from 2009 to 2012 (LS-502-1, LS-402-1Y, LS 312-1Y,
      LS-313-1Y, L-402, L-312) were found. Morphological findings were surface,
      subsurface, or deep calcifications of the IOL material. Explantation was
      performed 4 years +/- 1.2 (SD) after initial phacoemulsification. The mean
      patient age was 78.6 +/- 8.2 years. Ocular and systemic comorbidities were found
      without statistical correlation: the most frequent were diabetes, uveitis, and
      glaucoma. The preoperative mean corrected distance visual acuity changed from
      0.63 +/- 0.47 logarithm of the minimum angle of resolution (logMAR) to 0.20 +/-
      0.28 logMAR postoperatively (P < .001). CONCLUSIONS: Different designs of IOLs by
      the same manufacturer, implanted between 2009 and 2012, developed late
      calcification with significant visual loss after routine cataract surgery. No
      medical, surgical, or ophthalmologic trigger could be determined. A manufacture
      issue might be the reason for the opacification.

PMID- 30279088
TI  - Agreement between lens thickness measurements by ultrasound immersion biometry
      and optical biometry.
AB  - PURPOSE: To compare lens thickness measurements provided by immersion ultrasound
      (US) biometry and optical biometry. SETTING: IRCCS-Fondazione Bietti, Rome,
      Italy. DESIGN: Evaluation of diagnostic technology. METHODS: Immersion US
      biometry and optical biometry were performed in a consecutive series of eyes
      having cataract surgery. Three optical biometers (OA-2000, Aladdin, and Galilei
      G6) were used. To assess how the differences in lens thickness measurements
      influenced intraocular lens (IOL) power calculation, the lens thickness values
      were entered into the Olsen formula. RESULTS: Eighty-eight eyes were analyzed.
      Ultrasound immersion biometry yielded significantly higher lens thickness values
      than all of the optical biometers (P < .0001). The mean difference ranged between
      0.29 mm and 0.43 mm. Although the differences between the 3 optical biometers
      were smaller, they were still statistically significant (P < .001). With respect
      to the immersion US biometry, lens thickness measurements using the optical
      biometric measurements would have resulted in the selection of a lower IOL power
      in between 43.2% and 62.5% of eyes, depending on the optical biometer. Comparison
      of the measurements of the 3 optical biometers showed that a different IOL power
      would have been selected in between 9.1% and 19.3% of eyes. CONCLUSIONS: Lens
      thickness measurements by immersion US biometry and optical biometry cannot be
      considered interchangeable. Minor, but still significant, differences between the
      3 optical biometers tested were also found.

PMID- 30279089
TI  - Corrigendum to "Designing an immunocyte-targeting delivery system by use of beta
      glucan" [Vaccine 36 (2018) 186-189].

PMID- 30279091
TI  - Communication-based interventions for increasing influenza vaccination rates
      among Aboriginal children: A randomised controlled trial.
AB  - BACKGROUND: In Australia, the influenza vaccine is funded for Aboriginal and
      Torres Strait Islander (hereafter referred to as Aboriginal) children aged 6
      months to <5 years old. In Victoria, only 2% of Aboriginal children are
      vaccinated against influenza. OBJECTIVE: To evaluate whether sending a letter or
      sending a pamphlet directly to parents/guardians would improve influenza vaccine
      uptake amongst Aboriginal identified children. DESIGN: The study involved a multi
      arm, parallel, randomised controlled trial with two intervention groups and one
      control group. PARTICIPANTS & SETTING: Participants included parents or guardians
      of Victorian children (aged 6 months to <5 years) who identified as Aboriginal.
      Households (n = 5534) were randomised (using a random number generator) to
      receive either a personalised letter (n = 1845), a pamphlet (n = 1845), or no
      direct communication (control) (n = 1844). The letter and the pamphlet were
      designed using the INSPIRE framework - a set of behaviour change techniques for
      action-oriented communication. MAIN OUTCOME MEASURE: The proportion of households
      where all eligible children received the influenza vaccine between 2 May 2017 and
      1 September 2017. RESULTS: The control group's vaccination rate was 4.4%, higher
      than previous years. The pamphlet group achieved a similar vaccination rate
      (4.5%). The letter group's vaccination rate of 5.9% was significantly higher than
      the control group [chi2 (1, n = 3689) = 4.33, p = .037]. CONCLUSIONS: Sending a
      personalised letter directly to parents/guardians was an effective strategy for
      increasing influenza vaccination among Aboriginal children. The ineffectiveness
      of the pamphlet may be due to the lack of personalisation and the authority
      associated with the letter. Additional research is required to understand
      participant responses to the material. TRIAL REGISTRATION: This research was
      retrospectively registered with the Australian New Zealand Clinical Trials
      Registry (ANZCTR) on 13 September 2017 (ACTRN12617001315303).

PMID- 30279090
TI  - Memory inflation following adenoviral vaccination depends on IL-21.
AB  - Cytomegalovirus (CMV) and non-replicating adenoviral vectors can induce expanded,
      sustained effector-memory CD8+ T-cell responses, termed "memory inflation".
      During murine CMV (MCMV) infection, CD4+ Tcells maintain inflationary virus
      specific CD8+ T-cell responses via IL-2 but not IL-21. Adenovirus vector
      vaccination can induce phenotypically, functionally and transcriptionally similar
      inflationary responses, but it is not known how IL-21 influences the inflating
      memory response to adenoviral vaccination. Here, we show that IL-21 is an
      absolute requirement for induction and maintenance of vaccine-derived
      inflationary CD8+ T-cell responses. These data indicate that the induction
      pathway of inflationary Ad-LacZ T-cells is distinct from inflationary MCMV
      specific T-cells and is highly dependent on IL-21. Our observations highlight a
      fundamental difference in the mechanism by which adenovirus vectors and MCMV
      drive inflationary T-cell responses.

PMID- 30279092
TI  - Recognition and killing of Brugia malayi microfilariae by human immune cells is
      dependent on the parasite sample and is not altered by ivermectin treatment.
AB  - Mass administration of macrocyclic lactones targets the transmission of the
      causative agents of lymphatic filariasis to their insect vectors by rapidly
      clearing microfilariae (Mf) from the circulation. It has been proposed that the
      anti-filarial action of these drugs may be mediated through the host immune
      system. We recently developed an in vitro assay for monitoring the attachment to
      and killing of B. malayi Mf by human neutrophils (PMNs) and monocytes (PBMCs),
      however, the levels of both cell to worm attachment and leukocyte mediated Mf
      killing varied greatly between individual experiments. To determine whether
      differences in an individual's immune cells or the Mf themselves might account
      for the variability in survival, PMNs and PBMCs were isolated from 12 donors
      every week for 4 weeks and the cells used for survival assays with a different
      batch of Mf, thereby keeping donors constant but varying the Mf sample. Results
      from these experiments indicate that, overall, killing is Mf-rather than donor
      dependent. To assess whether ivermectin (IVM) or diethylcarbamazine (DEC)
      increase killing, Mf were incubated either alone or with immune cells in the
      presence of IVM or DEC. Neither drug induced a significant difference in the
      survival of Mf whether cultured with or without cells, with the exception of DEC
      at 2 h post incubation. In addition, human PBMCs and PMNs were incubated with IVM
      or DEC for 1 h or 16 h prior to RNA extraction and Illumina sequencing. Although
      donor-to-donor variation may mask subtle differences in gene expression,
      principle component analysis of the RNASeq data indicates that there is no
      significant change in the expression of any genes from the treated cells versus
      controls. Together these data suggest that IVM and DEC have little direct effect
      on immune cells involved in the rapid clearance of Mf from the circulation.

PMID- 30279093
TI  - Tel1 and Rif2 oppositely regulate telomere protection at uncapped telomeres in
      Saccharomyces cerevisiae.
AB  - It has been well documented that Tel1 positively regulates telomere-end resection
      by promoting Mre11-Rad50-Xrs2 (MRX) activity, while Rif2 negatively regulates
      telomere-end resection by inhibiting MRX activity. At uncapped telomeres, whether
      Tel1 or Rif2 plays any role remains largely unknown. In this work, we examined
      the roles of Tel1 and Rif2 at uncapped telomeres in yku70Delta and/or cdc13-1
      mutant cells cultured at non-permissive temperature. We found that deletion of
      TEL1 exacerbates the temperature sensitivity of both yku70Delta and cdc13-1
      cells. Further epistasis analysis indicated that MRX and Tel1 function in the
      same pathway in telomere protection. Consistently, TEL1 deletion increases
      accumulation of Exo1-dependent telomeric single-stranded DNA (ssDNA) at uncapped
      telomeres, which stimulates checkpoint-dependent cell cycle arrest. Moreover,
      TEL1 deletion in yku70Delta cells facilitates Rad51-dependent Y' recombination.
      In contrast, RIF2 deletion in yku70Delta cells decreases the accumulation of
      telomeric ssDNA after 8 h of incubation at the non-permissive temperature of 37 
      degrees C and suppresses the temperature sensitivity of yku70Delta cells, likely
      due to the increase of Mre11 association at telomeres. Collectively, our findings
      indicate that Tel1 and Rif2 regulate telomere protection at uncapped telomeres
      via their roles in balancing MRX activity in telomere resection.

PMID- 30279094
TI  - Characterization of a novel regulatory pathway for mannitol metabolism and its
      coordination with biofilm formation in Mycobacterium smegmatis.
AB  - Biofilm formation has been implicated to be tightly regulated in bacteria.
      Mycobacterial species possess a unique cell-wall structure; however, the
      underlying regulation mechanism for their biofilm formation remains largely
      unclear. In this study, we characterized a hypothetical mannitol metabolism and
      transportation gene cluster (Ms5571-Ms5576), designated as mmt operon, whose
      expression significantly contributes to the biofilm formation in Mycobacterium
      smegmatis. We showed that in the operon the Ms5575 gene encodes a GntR-like
      transcriptional repressor and the Ms5576 gene encodes a mannitol 2-dehydrogenase
      which can produce D-mannitol from D-mannose. Strikingly, the D-mannitol molecule
      can derepress the negative regulation of Ms5575 on the mmt operon to stimulate
      the operon's expression. Consistently, addition of D-mannitol into the medium can
      obviously induce mycobacterial biofilm formation. Furthermore, we found that
      Ms0179 positively regulates the mmt operon through its downstream regulator
      Ms0180. Ms0180 directly binds the mmt operon to positively regulate its
      expression. Both Ms0179 and Ms0180 significantly affect the mycobacterial biofilm
      formation. Taken together, we explored a regulatory pathway for the mannitol
      metabolism and its coordination with the biofilm formation in M. smegmatis. This
      finding provides novel insights into the unique mechanism of biofilm formation
      regulation in mycobacteria.

PMID- 30279096
TI  - Neuronatin deletion causes postnatal growth restriction and adult obesity in
      129S2/Sv mice.
AB  - OBJECTIVE: Imprinted genes are crucial for the growth and development of fetal
      and juvenile mammals. Altered imprinted gene dosage causes a variety of human
      disorders, with growth and development during these crucial early stages strongly
      linked with future metabolic health in adulthood. Neuronatin (Nnat) is a
      paternally expressed imprinted gene found in neuroendocrine systems and white
      adipose tissue and is regulated by the diet and leptin. Neuronatin expression is
      downregulated in obese children and has been associated with stochastic obesity
      in C57BL/6 mice. However, our recent studies of Nnat null mice on this genetic
      background failed to display any body weight or feeding phenotypes but revealed a
      defect in glucose-stimulated insulin secretion due to the ability of neuronatin
      to potentiate signal peptidase cleavage of preproinsulin. Nnat deficiency in beta
      cells therefore caused a lack of appropriate storage and secretion of mature
      insulin. METHODS: To further explore the potential role of Nnat in the regulation
      of body weight and adiposity, we studied classical imprinting-related phenotypes
      such as placental, fetal, and postnatal growth trajectory patterns that may
      impact upon subsequent adult metabolic phenotypes. RESULTS: Here we find that, in
      contrast to the lack of any body weight or feeding phenotypes on the C57BL/6J
      background, deletion of Nnat in mice on 129S2/Sv background causes a postnatal
      growth restriction with reduced adipose tissue accumulation, followed by catch up
      growth after weaning. This was in the absence of any effect on fetal growth or
      placental development. In adult 129S2/Sv mice, Nnat deletion was associated with
      hyperphagia, reduced energy expenditure, and partial leptin resistance. Lack of
      neuronatin also potentiated obesity caused by either aging or high fat diet
      feeding. CONCLUSIONS: The imprinted gene Nnat plays a key role in postnatal
      growth, adult energy homeostasis, and the pathogenesis of obesity via catch up
      growth effects, but this role is dependent upon genetic background.

PMID- 30279097
TI  - On the observation of lubrication mechanisms within hip joint replacements. Part
      II: Hard-on-hard bearing pairs.
AB  - The present paper represents Part II of the extensive study focused on the
      lubrication of hip joint replacements. The main goal is to assess the
      fundamentals of lubrication considering both hard-on-soft (Part I) and hard-on
      hard (Part II) bearing pairs. In addition, the effect of individual constituents
      contained in the model fluid is clarified. For this purpose, multiple model
      fluids of various composition were employed. In this part of the study, metal-on
      glass contact representing hard bearing pairs was observed in situ using pendulum
      hip joint simulator in combination with thin film colorimetric interferometry
      method. The designed test consists of initial static loading/unloading phase for
      the determination of adsorption of molecules on rubbing surfaces. This period is
      followed by swinging of the pendulum and latest static part under constant load.
      Three groups of measurements were carried out while fourteen different lubricants
      were tested. Initially, the experiments were performed with albumin-based model
      fluid. In that case a substantial positive effect of hyaluronic acid was
      identified. In contrast, the fluids with gamma-globulin as a base constituent
      showed improved lubrication conditions when phospholipids were added to the
      solution. Finally, considering the complex fluid, a combined effect of hyaluronic
      acid and phospholipids caused a better endurance of the lubricant film. The
      latest part of the paper aims on the comparison of film formation considering
      hard and soft pairs, highlighting some clear differences. In general, hard pairs
      exhibit clear decreasing tendency of the film during swinging motion while
      opposite behaviour was observed for soft pairs.

PMID- 30279098
TI  - Immunosuppressive burden and risk factors of infection in primary childhood
      nephrotic syndrome.
AB  - INTRODUCTION: Patients with primary childhood nephrotic syndrome (PCNS) develop
      alterations in their cellular and humoral immunity that predisposes them to the
      development of infection, and lead them to have frequent relapses. Also,
      infection could be significantly enhanced by immunosuppressive agents. This study
      aims to estimate the immunosuppressive burden, rate of infection and identify
      possible risk factors in PCNS requiring hospitalization. METHODOLOGY: A cross
      sectional study of hospitalized children<=14years of age diagnosed with PCNS in
      King Abdul-Aziz Medical City, Riyadh from January 2003 to December 2013. RESULT:
      Out of 111 patients admitted with PCNS, 84 (76%) had both minor and major types
      of infection. Upper respiratory tract infection (URTI) was the most predominant
      type (n=44, 52%). Among the major types of infection, urinary tract infection
      (UTI) was the most common infection (n=21, 25%) followed by pneumonia (n=17, 20%)
      then cellulitis (n=6, 6%). Infection in children who received a higher annual
      cumulative dose of steroids (CDS) strikingly had a higher rate of infection in
      comparison to those who received lower CDS (p<0.01). Moreover, those who received
      primary and secondary immunosuppressant's had 100% infection rate. CONCLUSION:
      About half of infection encountered by PCNS patients were URTI followed by UTI
      and pneumonia. Higher annual CDS, combination of primary and secondary
      immunosuppressants were the highest independent risk factors for infection. Among
      the infection, URTI was considered as the predominant entity whereas among the
      major infection, UTI was predominant followed by pneumonia then cellulitis.

PMID- 30279095
TI  - Obstructive sleep apnea and the metabolic syndrome: The road to clinically
      meaningful phenotyping, improved prognosis, and personalized treatment.
AB  - Obstructive sleep apnea (OSA) is an increasingly prevalent sleep disorder
      characterized by upper airway obstruction during sleep, resulting in breathing
      pauses, intermittent hypoxia, and fragmented sleep. In parallel, the
      constellation of adverse health outcomes associated with prolonged obesity, such
      as insulin resistance, elevated blood pressure, triglycerides, and reduced high
      density lipoprotein cholesterol - termed metabolic syndrome -raises the risk of
      cardiovascular morbidity and mortality, type 2 diabetes, and all-cause mortality.
      Affecting 35-40% of U.S. adults, risk factors for metabolic syndrome, including
      obesity, middle age, sedentary behavior, and genetics, share considerable overlap
      with those for OSA. Thus, it has been difficult to disentangle cause, effect, and
      whether certain treatments, such as CPAP, can improve these outcomes. In this
      paper, we provide an update to our 2005 review which explored the association
      between OSA and metabolic syndrome, highlighting visceral obesity as the common
      etiological factor of both conditions. This update includes (a) recent data on
      physiological and biochemical mechanisms, (b) new data in nonobese men and women
      as well as children and adolescents, (c) insight from the latest treatment
      studies, (d) the role of aging in understanding clinically-meaningful phenotypes
      of the disorder, and (e) the potential diagnostic/prognostic utility of
      biomarkers in identifying OSA patients with the strongest cardiometabolic risk.

PMID- 30279099
TI  - Treatment of peristomal hemorrhage: A review of outcomes and comparison of two
      minimally invasive techniques.
AB  - PURPOSE: The purpose of this study was to review and compare outcomes between
      percutaneous sclerotherapy and transjugular intrahepatic portosystemic shunt
      (TIPS) treatments in patients with peristomal variceal bleeding. MATERIALS AND
      METHODS: Ten patients who underwent sclerotherapy (n = 3 patients), TIPS
      placement (n = 5 patients) or both (n= 2 patients) for peristomal variceal
      bleeding were retrospectively reviewed. There were 6 women and 4 men, with a mean
      age of 62.6 years (range: 44-84 years). Data pertaining to the technical aspects
      of the procedure, demographics, and information regarding the underlying cause of
      ostomy and portal hypertension were collected. Treatment was considered a primary
      success if no further hemorrhage occurred. RESULTS: No differences in primary
      success were found between TIPS cohort (100%) and sclerotherapy cohort (40%)
      (P=0.4). Sclerotherapy patients had a poorer nutritional status (mean albumin
      serum level of 2.04g/dL in the sclerotherapy group and 2.95g/dL in theTIPS group;
      P=0.04) and worse liver function (mean total bilirubin serum level of 4.9mg/dL in
      the sclerotherapy group and 1.6mg/dL in the TIPS group; P=0.07). CONCLUSION:
      While further investigation is needed, TIPS may be more effective than
      sclerotherapy in treating peristomal variceal bleeding. However, sclerotherapy
      may serve as an effective bridging mechanism in critically ill patients.

PMID- 30279100
TI  - Increasing ethanol yield through fiber conversion in corn dry grind process.
AB  - Conversion of corn fiber to ethanol in the dry grind process could increase
      ethanol yields, reduce downstream processing costs and improve overall process
      profitability. This work investigates the in-situ conversion of corn fiber into
      ethanol (cellulase addition during simultaneous saccharification and
      fermentation) during dry grind process. Addition of 30 FPU/g fiber cellulase
      resulted in 4.6% increase in ethanol yield compared to the conventional process.
      Use of excess cellulase (120 FPU/g fiber) resulted in incomplete fermentation and
      lower ethanol yield compared to the conventional process. Multiple factors
      including high concentrations of ethanol and phenolic compounds were responsible
      for yeast stress and incomplete fermentation in excess cellulase experiments.

PMID- 30279101
TI  - Nitrogen removal through "Candidatus Brocadia sinica" treating high-salinity and
      low-temperature wastewater with glycine addition: Enhanced performance and
      kinetics.
AB  - Freshwater-derived anaerobic ammonia oxidation (anammox) bacteria ("Candidatus
      Brocadia sinica") were investigated to remove nitrogen from high-salinity and low
      temperature wastewater with glycine addition. The reactor was operated at 15 +/-
      0.5  degrees C with influent pH of 7.5 +/- 0.1. When glycine were 0.2, 0.4, and
      0.6 mM, respectively, nitrite removal rate (NRR) increased by 27.7%, 47.3%, and
      70.4% accordingly. Optimal ammonia removal rate (0.32 kg/(m3.d)) and NRR (0.45
      kg/(m3.d)) were achieved at 0.8 mM glycine. Effect resulting from glycine on
      nitrite reductase was higher than hydrazine synthase. Moreover, DeltaNO2-
      N/DeltaNH4+-N increased with glycine addition while DeltaNO3--N/DeltaNH4+-N first
      increased and then decreased. The remodified Logistic model and modified
      Boltzmann model were appropriate to describe nitrogen removal with glycine
      addition. Kinetic parameter lambda achieved through the remodified Logistic model
      revealed that "Candidatus Brocadia sinica" had a shorter lag phase than that of
      marine anammox bacteria.

PMID- 30279102
TI  - [Who will guard the guardians?]

PMID- 30279103
TI  - The Effect of Surgical Treatment for Gynecomastia on Quality of Life in
      Adolescents.
AB  - PURPOSE: Despite the psychosocial deficits associated with gynecomastia, surgical
      treatment of adolescent gynecomastia remains controversial. This longitudinal
      cohort study measures changes in health-related quality of life following
      surgical treatment of gynecomastia in adolescents. METHODS: The following surveys
      were administered to adolescents with gynecomastia and male controls, aged 12-21
      years: Short-Form 36v2 (SF-36), Rosenberg Self-Esteem Scale (RSES), and Eating
      Attitudes Test-26. Subjects completed surveys at baseline and postoperatively/at
      follow-up at 6 months, 1 year, 3 years, and 5 years. RESULTS: From 2008 to 2017,
      44 patients undergoing surgical treatment of gynecomastia and 64 unaffected male
      controls participated in our study. At baseline, gynecomastia patients scored
      significantly worse than controls on the RSES and in five SF-36 domains: general
      health, vitality, social functioning, role-emotional, and mental health. Scores
      significantly improved postoperatively on the RSES, and in four SF-36 domains:
      physical functioning, role-physical, bodily pain, and social functioning.
      Postoperatively, gynecomastia subjects scored similarly to controls in all SF-36
      domains and the RSES. Young and overweight/obese patients and those with severe
      gynecomastia had the greatest postoperative improvement across survey measures.
      CONCLUSIONS: Surgical treatment of gynecomastia significantly improves the
      quality of life of adolescents, with measurable improvements in physical and
      psychosocial functioning. Postoperatively, gynecomastia patients performed
      comparably to unaffected controls. Surgical treatment of gynecomastia in
      adolescents and young men has the potential to significantly improve quality of
      life, particularly in younger and overweight/obese patients and those with
      moderate to severe gynecomastia. Concerns regarding patient age and body mass
      index alone should not contraindicate surgery.

PMID- 30279104
TI  - Somatic Symptom Disorders in Adolescent Inpatients.
AB  - PURPOSE: There are only a few reports of adolescents with somatic disorders (SDs)
      whose symptoms are sufficiently severe to require hospital admission. The aim of
      this study was to describe the symptom profile, health service utilization, and
      outcome of adolescents with SDs admitted to a tertiary children's hospital.
      METHODS: A retrospective cohort study of all adolescents admitted to the
      Adolescent Medicine Unit of a tertiary children's hospital was undertaken from
      July 2013 to June 2014. In a two-stage process, medical records were examined to
      identify patients who met the diagnostic criteria for SD. Evidence of functional
      recovery was obtained for the period from 18 to 30 months after discharge and
      rated as completely recovered, partially recovered, or functionally disabled.
      RESULTS: A total of 60 admissions (53 patients, 79% female) were identified with
      SD, accounting for 12% of the unit's admissions and 2% of hospital admissions
      over 12 years old. Nearly half (45%) the presenting symptoms were neurological
      and 39% involved pain. In total, 20% of admissions were for complex symptoms
      involving multiple body systems. The majority (81%) of adolescents with follow-up
      documentation (n = 37) demonstrated complete or partial recovery. Patients whose
      families fully accepted the diagnosis were more likely to accept counseling
      following discharge (p < .001) and were almost 20 times more likely to have
      completely recovered compared to adolescents whose families partially accepted or
      rejected the diagnosis (odds ratio 17.36, p = .003). CONCLUSIONS: Hospitalized
      adolescents with SD utilize substantial resources due to the requirement for
      comprehensive assessment, including multidisciplinary communication. Recovery can
      be anticipated for the majority, especially if supported by parents.

PMID- 30279105
TI  - Longitudinal Change in Parent-Adolescent Communication About Sexuality.
AB  - PURPOSE: Research suggests that parents can be important sources of sex education
      for their children, but we know little about how this type of communication
      changes developmentally. Thus, the current study explored longitudinal change in
      child-, mother-, and father-reports of parent-child communication about
      sexuality, and how change might be associated with behaviors indicative of sexual
      risk. METHODS: The sample included 468 adolescents (52% female, 67% white) who
      participated every year from age 14 to 18, and their mother and father. RESULTS:
      Growth-curve analyses revealed relatively low and stable levels of parent-child
      communication from all three reporters, with some differences as a function of
      reporter and child gender. Results also suggested that initial levels and change
      in parent-child communication over time were associated with child-reports of
      safer sex at the final time point (age 21). CONCLUSIONS: The discussion focuses
      on developmental approaches to parent-child sex communication and the need for
      future research.

PMID- 30279106
TI  - An alternative approach to the intraoperative Indocyanine Green angiography
      (ICGA) in reconstructive surgery.

PMID- 30279107
TI  - The Helsinki approach to face transplantation.
AB  - AIM: We herein describe the establishment of the Helsinki Vascularized Composite
      Allotransplantation (VCA) program and its execution in the first two face
      transplant cases. METHODS & PATIENTS: The Helsinki VCA program initially required
      the fulfillment of legal, hospital, financial, and ethical requirements.
      Thereafter, the assembling of a multidisciplinary team commenced. A team of
      Plastic, maxillofacial and ENT surgeons comprise the facial VCA team. The
      protocol involves collaboration with the Solid Organ Transplant (SOT) team,
      transplant immunology, immunosuppression, microbiology, psychiatric evaluation,
      well-defined VCA indications and informed consent. Between 2011 and 2017 two
      patients were selected for transplantation. Both patients had a severe composite
      facial deformity involving the maxilla and mandible following earlier ballistic
      injury. RESULTS: Patient 1 was a 35 year-old male who underwent successful near
      total face transplantation in February 2016 and at 30 months he has a good
      aesthetic outcome with symmetrical restoration of the central face and good
      sensory and symmetrical motor functional outcomes. Patient 2 was a 58 year-old
      male who underwent full face transplantation in March 2018 and at 5 months he has
      recovered without major problems. CONCLUSION: A successful facial VCA program
      requires a well-prepared research protocol, experts from multiple specialties and
      careful patient selection. The establishment of the Helsinki VCA program required
      long and thorough planning and resulted in the first two Nordic face
      transplantation cases. This protocol now forms the platform (as a proof of
      concept) for other types of vascularized composite allotransplantations.

PMID- 30279108
TI  - Minimally Invasive Cardiac Surgery Without Peripheral Cannulation: A Single
      Centre Experience.
AB  - BACKGROUND: A minimally invasive approach without any peripheral cannulation was
      used as an alternative to median sternotomy for the correction of a wide range of
      cardiac defects with superior results and good cosmetic outcome. METHODS: From
      October 2015 to March 2017, 145 patients underwent correction of congenital
      cardiac malformations with cardiopulmonary bypass through right anterior
      minithoracotomy (RAMT) with routine cannulation. The average age was 9.69+/
      4.38years (range 2-21) and the average body surface area was 0.91+/-0.27square
      metres (range 0.5-1.7). The corrected defects included all types of atrial septal
      defect (ASD) and ventricular septal defects (VSD), partial atrioventricular
      septal defects with severe mitral regurgitation, mitral valve repair, repair of
      tetralogy physiology requiring outlet patch enhancement, isolated pulmonary
      stenosis (PS) and congenital coronary cameral fistula. RESULTS: There was no
      operative mortality or major morbidity. All patients were alive at the time of
      this follow-up. The mean cardiopulmonary bypass time was 64.75+/-22.28minutes
      (range 30-175) and mean aortic cross clamp time was 37.53+/-18.23minutes (range
      14-135). Fifty-five patients were extubated in the operating room and the
      remaining 90 patients were extubated within 3hours in the intensive care unit.
      Repair and cosmetic results were excellent in all patients. There were no
      conversions to full sternotomy. No neurological events were reported.
      CONCLUSIONS: Right anterior minithoracotomy without peripheral cannulation is
      safe and effective for the correction of a wide range of congenital heart defects
      including right ventricular outlet obstructions. The cosmetic results are
      satisfactory, avoiding psychosocial problems.

PMID- 30279109
TI  - Predictors of Distant Failure After Stereotactic Body Radiation Therapy for
      Stages I to IIA Non-Small-Cell Lung Cancer.
AB  - PURPOSE: The use of stereotactic body radiation therapy (SBRT) has emerged as an
      effective treatment modality for patients with early-stage non-small-cell lung
      cancer (NSCLC), with excellent local control rates. Despite this, there is a
      predominant pattern of distant failure. We sought to identify factors that help
      predict which patients with stages I to IIA NSCLC treated with SBRT are at
      highest risk of distant failure, so that we may utilize these factors in the
      future to help determine which patients may benefit from the addition of systemic
      therapies. PATIENTS AND METHODS: We retrospectively reviewed 292 patients treated
      with SBRT for early stage NSCLC from 2006 to 2016 at 2 institutions. Patients
      were classified by T stage, tumor size, location and histology, pretreatment
      positron emission tomography/computed tomography (PET/CT) standardized uptake
      value (SUV), smoking status, and age. The primary endpoint of the study was
      distant failure. We aimed to analyze if patient characteristics could be
      identified that predicted for distant failure through the use of competing risk
      analysis. RESULTS: The median follow-up was 21.9 months. The median dose of
      radiation and fractionation delivered was 50 Gy (range, 45-65 Gy) in 5 fractions
      (range, 3-13 fractions). The median patient age was 72.8 years (interquartile
      range, 65.4-79.7 years). The 2-year distant failure was 22.0%, and overall
      survival at 2 years was found to be 61.0%. For every 1-year increase in patient
      age, the hazard of distant failure at any given time was 3% lower (hazard ratio,
      0.97; 95% confidence interval, 0.94-0.99; P = .04). None of the remaining
      characteristics emerged as significant risk factors for distant failure on
      univariable or multivariable analysis. CONCLUSIONS: Overall, our cohort had
      distant failure and survival rates comparable with what has been described in the
      literature. Although we were unable to identify factors outside of age that
      correlated to risk of distant failure, this topic warrants further investigation,
      as distant failure is the primary pattern of failure with SBRT when used as the
      primary management for early-stage NSCLC. Additional molecular studies are needed
      to further inform on the role of systemic therapy in patients with early-stage
      NSCLC to improve clinical outcomes.

PMID- 30279110
TI  - Targeted Tissue and Cell-Free Tumor DNA Sequencing of Advanced Lung Squamous-Cell
      Carcinoma Reveals Clinically Significant Prevalence of Actionable Alterations.
AB  - BACKGROUND: Major guidelines do not recommend routine molecular profiling of lung
      squamous-cell carcinoma (LUSC) because the prevalence of actionable alterations
      is thought to be low. Increased utilization of next-generation sequencing (NGS),
      particularly with cell-free circulating tumor DNA, facilitates reevaluation of
      this premise. PATIENTS AND METHODS: We retrospectively evaluated the prevalence
      of actionable alterations in 2 distinct LUSC cohorts totaling 492 patients. A
      total of 410 consecutive patients with stage 3B or 4 LUSC were tested with a
      targeted cell-free circulating DNA NGS assay, and 82 patients with LUSC of any
      stage were tested with a tissue NGS cancer panel. RESULTS: In the overall cohort,
      467 patients (94.9%) had a diagnosis of LUSC, and 25 patients (5.1%) had mixed
      histology with a squamous component. A total of 10.5% of the LUSC subgroup had
      somatic alterations with therapeutic relevance, including in EGFR (2.8%),
      ALK/ROS1 (1.3%), BRAF (1.5%), and MET amplification or exon 14 skipping (5.1%).
      Sixteen percent of patients with mixed histology had an actionable alteration. In
      the LUSC subgroup, 3 evaluable patients were treated with targeted therapy for an
      actionable alteration; all of them experienced partial response. CONCLUSION: In
      this large, real-world LUSC cohort, we observed a clinically significant
      prevalence of actionable alterations. Accurate local histopathologic assessment
      in advanced-stage LUSC can be challenging. Further evaluation of the genomic
      landscape in this setting is warranted to potentially identify underappreciated
      treatment options.

PMID- 30279111
TI  - Cell-Free DNA Next-Generation Sequencing Prediction of Response and Resistance to
      Third-Generation EGFR Inhibitor.
AB  - INTRODUCTION: The genomic alterations driving resistance to third-generation EGFR
      tyrosine kinase inhibitors (TKIs) are not well established, and collecting tissue
      biopsy samples poses potential complications from invasive procedures. Cell-free
      circulating DNA (cfDNA) testing provides a noninvasive approach to identify
      potentially targetable mechanisms of resistance. Here we utilized a 70-gene cfDNA
      next-generation sequencing test to interrogate pretreatment and progression
      samples from 77 EGFR-mutated non-small cell lung cancer (NSCLC) patients treated
      with a third-generation EGFR TKI. PATIENTS AND METHODS: Rociletinib was evaluated
      in advanced or metastatic (second line or higher) disease with EGFR T790M
      positive NSCLC in the TIGER-X (NCT01526928) and TIGER-2 (NCT02147990) studies.
      Plasma samples were collected at baseline and at the time of systemic progression
      while receiving rociletinib. The critical exons in 70 genes were sequenced in
      cfDNA isolated from plasma samples to elucidate a comprehensive genomic profile
      of alterations for each patient. RESULTS: Plasma-based cfDNA analysis identified
      93% of the initial EGFR activating and 85% of the EGFR T790M resistance mutations
      in pretreatment samples with detectable tumor DNA. Profiling of progression
      samples revealed significant heterogeneity, with different variant types (eg,
      mutations, amplifications, and fusions) detected in multiple genes (EGFR, MET,
      RB1) that may be driving resistance in patients. Novel alterations not previously
      described in association with resistance to third-generation TKIs were also
      detected, such as an NTRK1 fusion. CONCLUSION: cfDNA next-generation sequencing
      identified initial EGFR activating and secondary T790M resistance mutations in
      NSCLC patients with high sensitivity, predicted treatment response equivalent to
      tissue analysis, and identified multiple novel and established resistance
      alterations.

PMID- 30279112
TI  - Emergence of a carbapenem-resistant and colistin-heteroresistant Enterobacter
      cloacae clinical isolate in Japan.
AB  - A carbapenem-resistant and colistin-heteroresistant clinical isolate of
      Enterobacter cloacae was obtained from an inpatient in Okinawa, Japan. The
      minimum inhibitory concentrations of both imipenem and meropenem were 32 MUg/mL.
      The isolate showed heteroresistance to colistin using the Etest method and
      resistance to colistin using the broth microdilution method. It had a disrupted
      ompC and a mutation in the promoter region of blaACT-2, but did not harbor any
      genes encoding carbapenemase. The disruption of ompC and the mutation in blaACT-2
      was associated with the carbapenem resistance of this isolate. This isolate also
      had mutations in pmrAB and phoPQ encoding two-component regulatory systems, which
      may be associated with colistin heteroresistance.

PMID- 30279113
TI  - Comparative analysis of methicillin-resistant Staphylococcus aureus isolated from
      outpatients of dermatology unit in hospitals and clinics.
AB  - Community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) is a
      causative agent of intractable skin infections. In general, clinical symptoms of
      hospital outpatients with skin infections are severer than those of clinic
      patients. Hence, molecular epidemiological features of the CO-MRSA strains from
      hospital outpatients are predicted to be different from those of clinic patients.
      Here, we conducted a comparative analysis for CO-MRSA isolates from outpatients
      with impetigo in hospitals and clinics located in the same district of Tokyo,
      Japan. Incidence of MRSA infection was higher in hospital outpatients (21.5%,
      20/93 isolates) than in clinic patients (14.5%, 121/845 isolates). The resistance
      rate to clindamycin, which is a common topical antimicrobial agent in
      dermatology, in the isolates from hospital outpatients (60.0%) was higher than
      those from clinic patients (31.4%). Proportion of the staphylococcal cassette
      chromosome (SCC) mec type II, which is a representative type of hospital-acquired
      MRSA in Japan, in the isolates from hospital outpatients (65.0%) was
      significantly higher than those from clinic patients (30.6%) (P < 0.01).
      Multilocus sequence typing showed that the clonal complex 89-SCCmec type II (CC89
      II) clone, which exhibits clindamycin resistance, was the most predominant
      (55.0%) in the isolates from hospital outpatients. On the other hand, all CC8-IV,
      CC121-V, and CC89-V clones accounted for 60% in clinic patients were susceptible
      to clindamycin. Our findings suggested that the clindamycin-resistant CC89-II CO
      MRSA clone might be more related to skin infections in hospital outpatients than
      clinic patients.

PMID- 30279114
TI  - Antimicrobial susceptibility of Streptococcus pneumoniae, Haemophilus influenzae,
      and Moraxella catarrhalis clinical isolates from children with acute otitis media
      in Japan from 2014 to 2017.
AB  - Increase in antimicrobial resistance (AMR) among pathogenic bacteria is a serious
      threat to public health. Surveillance studies to monitor shifting trends in
      resistance are important and guide the selection of appropriate antimicrobial
      agents for a particular organism. Furthermore, these studies help in
      dissemination of accurate information regarding AMR to the public. In this study,
      we investigated the antimicrobial susceptibility patterns of Streptococcus
      pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis clinical isolates
      from outpatient children with acute otitis media in Japan from 2014 to 2017. A
      total of 8693 strains (2415 of S. pneumoniae, 3657 of H. influenzae, and 2621 of
      M. catarrhalis) were clinically isolated, and their antimicrobial
      susceptibilities to benzylpenicillin (PCG), ampicillin (ABPC), amoxicillin
      clavulanic (AMPC/CVA), azithromycin (AZM), ceftriaxone (CTRX), and levofloxacin
      (LVFX) were investigated. Based on the minimum inhibitory concentration (MIC)
      breakpoints, the average proportion of S. pneumoniae isolates non-susceptible to
      PCG and AZM was 38.2% and 82.0% respectively. The average proportion of H.
      influenzae isolates non-susceptible to ABPC, CVA/AMPC, and CTRX was 61.9%, 43.5%,
      and 49.4%, respectively. The high prevalence of these resistant organisms is
      attributed to frequent use of antibiotic agents in Japan. Moreover, the
      proportion of LVFX-non-susceptible H. influenzae isolates increased in this four
      year study. Here, we report updates regarding the AMR trends amongst the major
      pathogens that cause acute otitis media in Japan. Continuing surveillance of
      antimicrobial susceptibility and application of control measures against further
      transmission are required to decrease the emergence of resistant strains.

PMID- 30279115
TI  - Denosumab Toxicity When Combined With Anti-angiogenic Therapies on Patients With
      Metastatic Renal Cell Carcinoma: A GETUG Study.
AB  - BACKGROUND: About one-third of patients with renal cell carcinoma (RCC) have
      detectable metastases at diagnosis. Among them, bone is the second most frequent
      metastatic site. Treatment of metastatic RCC mostly relies on anti-angiogenic
      (AA) therapies and, more recently, immunotherapy. Skeletal-related events (SREs)
      can be prevented with bone-targeted therapies such as denosumab (Dmab), which has
      demonstrated superiority when compared with zoledronic acid in solid tumors.
      However, there is limited available data on Dmab toxicity in combination with AA
      therapies in patients with kidney cancer. The objective of this study was to
      retrospectively analyze the toxicity profile (mainly osteonecrosis of the jaw
      [ONJ] and hypocalcemia) in patients with metastatic renal cell carcinoma (mRCC)
      treated with Dmab and AA therapy combination. PATIENTS AND METHODS: We conducted
      a multicenter retrospective study among centers from the French Groupe d'Etudes
      des Tumeurs Uro Genitales (GETUG). Patients with bone metastases who received
      concurrently or sequentially AA therapy and Dmab were included in this study.
      RESULTS: A total of 41 patients with mRCC were enrolled. Although no patient
      presented with severe hypocalcemia, ONJ occurred in 7 (17%) of 41 patients.
      Interestingly, all patients with ONJ received the Dmab and AA combination in the
      first line of treatment; among these patients, 3 patients had no risk factor
      other than the Dmab and AA combination. CONCLUSION: The incidence of ONJ was high
      in this real-life population of patients with mRCC treated with AA therapies
      combined with Dmab. This toxicity signal should warn physicians about this
      combination in the mRCC population.

PMID- 30279116
TI  - Paraneoplastic Syndrome Secondary to Treatment Emergent Neuroendocrine Tumor in
      Metastatic Castration-resistant Prostate Cancer: A Unique Case.

PMID- 30279117
TI  - The value of the Evans and bicaudate indices for predicting poor cognitive
      performance and central atrophy. Results from the Atahualpa Project.
AB  - Recent studies suggested that both the Evans index (EI) and the bicaudate index
      (BI) are predictive markers of central atrophy and, as such, have been inversely
      associated with cognitive performance. This study investigated whether the EI and
      the BI (independently and combined) correlated with the MoCA score by means of
      generalized linear models adjusted for relevant confounders. Using a population
      based design, 618 Atahualpa residents aged >=40 underwent a head CT and MoCA
      testing. Both, the EI and the BI, were independently calculated by two readers,
      and a mean of the two values for each index was calculated for analysis.
      Generalized linear models showed inverse significant relationships between the EI
      and the BI with the MoCA score (p = 0.034, and p < 0.001, respectively). When
      both predictive variables (EI and BI) were included in a generalized linear model
      adjusted for all confounders, the BI remained significantly associated with the
      MoCA score (p = 0.004) but the EI did not (p = 0.677). This study shows that only
      the BI has and explanatory power outside the endogenous construct (central
      atrophy) for which both, the BI and the EI are part and parcel of.

PMID- 30279118
TI  - Analysis for risk factors of 12-month neurological worsening in patients with
      surgically treated small-to-moderate size unruptured intracranial aneurysms.
AB  - The risk associated with surgical treatment for small-to-moderate size unruptured
      intracranial aneurysms (SMUIAs, defined as <15 mm) has not been well
      characterized. Authors aimed to investigate risk factors for poor outcome in
      surgical treatment of SMUIAs. The data of prospectively collected 801 consecutive
      patients harboring 971 surgically treated SMUIAs was evaluated. Neurological
      worsening (NW) was defined as an increase in 1 or more modified Rankin Scale at
      12-month. Clinical and radiological characteristics were compared. Neurological
      worsening was observed in 45 (4.6%). In multivariate analysis, only perforator
      territory infarction (PTI) on postoperative diffusion-weighted imaging (odds
      ratio (OR), 13; 95% confidence interval (CI), 4.9-32, p < 0.0001), and aneurysm
      locations (paraclinoid (OR, 6.9; 95% CI, 3.1-15, p < 0.0001), basilar artery (OR,
      4.5; 95% CI, 1.5-14, p = 0.008), vertebral artery (OR, 11; 95% CI, 3.3-34, p <
      0.0001)) were related to neurological worsening. Multivariate analysis showed
      that statin use (OR, 12; 95% CI, 3.8-39, p < 0.0001) and aneurysm locations
      (internal carotid artery-posterior communicating artery (OR, 3.9; 95% CI, 1.8
      8.2, p < 0.0001) and basilar artery (OR, 6.3; 95% CI, 2.3-17, p = 0.008)), and
      aneurysm size >10 mm (OR, 5.3; 95% CI, 1.8-15, p = 0.003) were related to PTI.
      Although all SMUIAs should be carefully considered whether to be treated, those
      with statins, specific locations, and larger sizes should perhaps be more
      meticulously contemplated, and neurosurgeons should continue to avoid PTI.

PMID- 30279119
TI  - Pre-operative planning and rod customization may optimize post-operative
      alignment and mitigate development of malalignment in multi-segment posterior
      cervical decompression and fusion patients.
AB  - : Patient-specific rods designed based on a particular pre-operative plan are a
      recent advancement to help achieve desired operative alignment goals. This study
      investigated the role of pre-operative planning and patient-specific rods on post
      operative alignment and outcomes. Patients were grouped according to use of pre
      operative planning and patient-specific, pre-contoured rods (PLAN) or absence of
      planning/rods (NON). Pre-operative and post-operative alignment were measured:
      cervical sagittal vertical axis (cSVA), cervical lordosis (CL), T1 Slope minus CL
      (TS-CL). Alignment differences between the groups were assessed using independent
      and paired samples t-tests. 34 patients were identified (15 PLAN, 19 NON). Pre-
      and post-operative CL, cSVA and TS were similar between the two groups (p >
      0.05), though pre-operative TS-CL was slightly higher in PLAN patients (28.13
      degrees  versus 18.42 degrees , p = 0.049). There were no improvement differences
      pre- to post-operative for CL, cSVA and TS between the groups (p > 0.05).
      However, PLAN patients exhibited a greater correction of TS-CL, with an average
      of 5.8 degrees  decrease versus a 3.5 degrees  increase in TS-CL for NON patients
      (p = 0.015). PLAN patients did not demonstrate a significant change from pre- to
      post-operative alignment for cSVA or TS-CL (cSVA: 27.5 mm to 31.1 mm, p = 0.255;
      TS-CL: 28.1 degrees  to 22.3 degrees , p = 0.13), though their TS-CL did trend
      towards significant post-operative improvement. In contrast, NON patients
      worsened in cSVA and TS-CL post-operatively (cSVA: 21.8 mm to 30.3 mm, p < 0.001;
      TS-CL: 18.4 degrees  to 22.0 degrees , p = 0.035). Multi-segment posterior
      decompression and fusion patients have the potential to worsen with regards to
      post-operative alignment without pre-operative planning. Patients with pre
      contoured rods and pre-operative planning exhibited a greater correction of TS-CL
      after surgery than un-planned cases, though limited by the pre-operative
      difference in cervical-thoracic mismatch between planned and unplanned cases.
      LEVELS OF EVIDENCE: III.

PMID- 30279120
TI  - Preoperative embolization of skull base meningiomas: A systematic review.
AB  - Neoadjuvant endovascular embolization of skull base meningiomas may facilitate
      surgical resection, thereby potentially decreasing operative morbidity. However,
      due to variation in the reported efficacy and complication rates, the utility of
      embolization remains incompletely defined. The aim of this systematic review is
      to assess the outcomes of preoperative embolization for skull base meningiomas. A
      literature review was performed to identify studies reporting outcomes of
      patients with skull base meningiomas who underwent preoperative embolization.
      Baseline, treatment, and outcomes data were analyzed. Major complications
      included death, new cranial neuropathy, retinal artery ischemia, permanent
      neurologic deficit, or intracerebral hemorrhage. The pooled analysis consisted of
      15 studies, comprising a total of 403 patients with skull base meningiomas
      treated with preoperative embolization. The most common locations were the
      sphenoid wing (34%, 87/256 cases), petroclival region (31%, 80/256 cases), and
      cavernous sinus (12%, 31/256 cases). The median tumor size ranged from 5.0 to 8.0
      cm. Based on pooled data, angiographic absence of tumor blush was achieved in 17%
      (13/79 cases). The median estimated blood loss (EBL) ranged from 225 to 580 mL.
      Simpson grade I-III resection was achieved in 74% (40/54) of patients. The
      overall complication, major complication, and mortality rates were 12% (47/403
      patients), 6% (21/328 patients), and 0.2% (1/403 patients), respectively.
      Preoperative embolization is a reasonable adjunct to resection for appropriately
      selected skull base meningiomas. Future comparative analyses are necessary to
      ascertain the benefits of preoperative embolization of skull base meningiomas
      with respect to extent of resection, operative duration, operative blood loss,
      and surgical morbidity.

PMID- 30279121
TI  - Letter to the editor regarding the manuscript "Lactate dehydrogenase as a
      prognostic marker in neoplastic meningitis".

PMID- 30279122
TI  - Chiari malformation clusters describe differing presence of concurrent anomalies
      based on Chiari type.
AB  - Chiari malformations are structural defects in the posterior fossa where the
      cerebellum displaces caudally into the foramen magnum and upper spinal canal.
      These malformations are classified by severity as Types 1-4, each presenting with
      different associated and/or concurrent conditions and anomalies. The aim of this
      study was to utilize a nationwide database to study patients with Chiari
      malformations including their concurrent diagnoses and associated anomalies.
      Using a retrospective review of the Nationwide Inpatient Sample (NIS) database
      from 2003 to 2012, Chiari malformations were assessed by Chiari type and rates of
      concurrence for various additional anomalies were evaluated using cross
      tabulations. There were 305,726 national cases of Chiari Type 1, 119,632 cases of
      Chiari Type 2, 15,540 cases of Type 3, and 79,663 cases of Type 4. Overall 44.3%
      of Chiari patients have at least one concurrent anomaly. Stratified by Chiari
      Type, 7.1% of Type 1 patients, 12.3% of Type 2, and 100% of Type 3 and 4 have at
      least one concurrent anomaly. The most common isolated neurologic associations
      were tethered cord, syringomyelia, and hydrocephalus, while the most common
      anomaly clusters were syringomyelia and scoliosis in Type 1 (0.63), tethered cord
      syndrome and scoliosis (0.72%) in Type 2, encephalocele and acquired
      hydrocephalus (11.45%) in Type 3, and reduction deformity of the brain with
      acquired hydrocephalus (15.95%) in Type 4. Chiari malformations have strong
      associations with other abnormalities outside of known relationships in the
      current classification. While neurologic abnormalities are most common,
      additional body systems are frequently involved especially with worsening
      hindbrain defects.

PMID- 30279123
TI  - Surgical decision-making in degenerative cervical myelopathy - Anterior versus
      posterior approach.
AB  - Surgery is the only effective treatment option for advanced degenerative cervical
      myelopathy. Decompression may be achieved via either an anterior or posterior
      approach. They are both well-established techniques that are used to achieve
      optimal clinical results with each approach having its own pros and cons.
      Generally, the approach is dictated by preoperative imaging features with the aim
      of directly addressing the sources of spinal cord compression. However, there are
      frequently multiple sources of compression and several other factors should be
      also considered. The posterior approach is optimal for multilevel stenosis using
      consecutive laminectomies. Conversely, in cases of rigid kyphosis, the anterior
      approach is preferable as it enables thorough decompression and lordotic
      realignment. The existence of radiculopathy, neck pain and dysphagia should be
      carefully considered, and patients' occupational and cosmetic demands must be
      also discussed given the risk of voice change and scar formation. Body habitus or
      previous history of skin incision or radiation may also influence the decision.
      Since the clinical benefit seems to be similar between the two approaches, the
      decision has to be made on a case-by-case basis depending on the surgeons'
      experiences and preferences.

PMID- 30279124
TI  - Phenotypic spectrum of patients with cystic fibrosis and cystic fibrosis-related
      disease carrying p.Arg117His.
AB  - BACKGROUND: The "mild" gene variant, p.Arg117His in cystic fibrosis (CF) results
      in highly variable phenotypes ranging from male infertility to severe lung
      disease. Due to current interest to include this group in CFTR-targeted
      therapies, this study aims to describe the disease spectrum. METHODS:
      Retrospective study of Toronto CF and CFTR-related p.Arg117His patients.
      Longitudinally captured clinical data were compared between patients with 5T/7T
      variants and those with a CF or CFTR-related diagnosis. Comparison was made
      between p.Arg117His adults and infants identified through CF newborn screening
      (NBS). RESULTS: Twenty of fifty patients carried the 5T variant, all with a
      diagnosis of CF (p.Arg117His-5TCF), and 30/50 carried 7T, 7 diagnosed with CF
      (p.Arg117His-7TCF) and 23 with a CFTR-related disorder (p.Arg117His-7TCFTR). For
      those with chest HRCT results available, 75% p.Arg117His-5TCF, 33% p.Arg117His
      7TCF and 27% p.Arg117His-7TCFTR patients had bronchiectasis. Further, 79%
      p.Arg117His-5T, 29% p.Arg117His-7TCF and 13% p.Arg117His-7TCFTR had abnormal lung
      function. Of those, 80% grew CF-related pathogens on respiratory culture.
      Interestingly, the mean maximum sweat chloride and the percentage of patients
      growing CF-related bacterial pathogens were identical in p.Arg117His-7 TCFTR
      adults and p.Arg117His infants. CONCLUSIONS: Generally, p.Arg117His-5T patients
      had more severe CF disease. However, a subset of p.Arg117His-7 T patients
      demonstrated equally severe disease, thus warranting clinical monitoring of all
      p.Arg117His patients including p.Arg117His infants identified via NBS.

PMID- 30279125
TI  - IVACAFTOR restores FGF19 regulated bile acid homeostasis in cystic fibrosis
      patients with an S1251N or a G551D gating mutation.
AB  - OBJECTIVE: Disruption of the enterohepatic circulation of bile acids (BAs) is
      part of the gastrointestinal phenotype of cystic fibrosis (CF). Ivacaftor (VX
      770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator,
      improves pulmonary function in CF patients with class III gating mutations. We
      studied the effect of ivacaftor on the enterohepatic circulation by assessing
      markers of BA homeostasis and their changes in CF patients. METHODS: In CF
      patients with an S1251N mutation (N = 16; age 9-35 years S125N study/NTR4873) or
      a G551D mutation (N = 101; age 10-24 years; GOAL study/ NCT01521338) we analyzed
      plasma fibroblast growth factor 19 (FGF19) and 7alpha-hydroxy-4-cholesten-3-one
      (C4) levels, surrogate markers for intestinal BA absorption and hepatic
      synthesis, respectively, before and after treatment with ivacaftor. RESULTS: At
      baseline, median FGF19 was lower (52% and 53%, P < .001) and median C4 higher
      (350% and 364%, P < .001), respectively, for the S1251 N and G551D mutation
      patient groups compared to healthy controls. Treatment with ivacaftor
      significantly increased FGF19 and reduced C4 levels towards normalization in both
      cohorts but this did not correlate with CFTR function in other organs, as
      measured by sweat chloride levels or pulmonary function. CONCLUSIONS: We
      demonstrate that patients with CFTR gating mutations display interruption of the
      enterohepatic circulation of BAs reflected by lower FGF19 and elevated C4 levels.
      Treatment with ivacaftor partially restored this disruption of BA homeostasis.
      The improvement did not correlate with established outcome measures of CF,
      suggesting involvement of modulating factors of CFTR correction in different
      organs.

PMID- 30279126
TI  - 20th National Voice Campaign.

PMID- 30279127
TI  - Gene expression profiles of Pyropia yezoensis in response to dehydration and
      rehydration stresses.
AB  - Pyropia yezoensis is an economically important marine macroalgae, naturally
      distributed in the upper intertidal zone. Owing to the nature of its habitat, the
      thallus will periodically be exposed to seawater or atmosphere, and can lose up
      to 95% of its cellular water content. This makes the alga an ideal research model
      to investigate the mechanisms of desiccation tolerance. In this study, we
      investigated the response mechanisms to dehydration and rehydration stresses at
      the transcription level in Pyropia yezoensis. The differently expressed genes
      were analyzed based on the different functions of encoding proteins: effector
      proteins (chloroplast proteins, macromolecular protective substances, and
      toxicity degradation enzymes) and regulatory proteins (protein kinases and
      phosphatases). Under osmotic stress, the unigenes related to photosynthesis were
      down-regulated significantly while those encoding glutathione transferase,
      superoxide dismutase and heat shock proteins were up-regulated significantly. We
      inferred that the photosynthetic activity was reduced to prevent damage caused by
      photosynthetic by-products and that the expression of antioxidant enzyme was
      increased to prevent the damage associated with reactive oxygen species.
      Additionally, unigenes encoding serine/threonine kinases and phospholipases were
      up-regulated in response to osmotic stress, indicating that these kinases play an
      important role in osmotolerance. Our work will serve as an essential foundation
      for the understanding of desiccation tolerance mechanisms in Pyropia yezoensis in
      the upper intertidal zones of rocky coasts.

PMID- 30279128
TI  - Spatial analysis of disparities in asthma treatment among adult asthmatics.
AB  - BACKGROUND: Spatial analytic techniques can uncover important differences in
      asthma treatment and identify geographic areas with poor asthma management.
      OBJECTIVE: To review geographical differences in asthma treatment in an adult
      asthmatic population. METHODS: This was a retrospective, cross-sectional chart
      review study (n = 519) using Geographic Information System approaches to
      determine the impact of spatial access to pharmacies and other factors on
      inappropriate rescue and inadequate controller medication use. Statistical
      analyses included chi-square test for categorical variables and Kruskall-Wallis
      test for continuous variables. Logistic regression was used to determine
      unadjusted and adjusted odds of inappropriate and inadequate pharmaceutical
      management of asthma based upon distance to pharmacy and other factors.
      Choropleth maps were constructed to display zip code level variation of asthma
      management. RESULTS: Inappropriate medication users lived further from their
      preferred pharmacy compared to appropriate users (median distances of 3.02 and
      1.96 miles respectively; p = 0.01). Inappropriate and inadequate management of
      asthma varied by zip code, ranging from 5.5 to 17.3% and 25.0-59.6%,
      respectively. A statistically significant difference in appropriate use by age
      was found, with nearly 17% of adults age 65 and older overusing their rescue
      inhaler. Conversely, patients age 18-34 years, 35-49 years, and 50-64 years, used
      their controller medications inadequately (64.2%, 57.3%, and 48.2%, respectively)
      compared to 42.5% of patients aged 65 and older. Unadjusted and adjusted analyses
      showed that former smokers had higher odds of inadequate management of asthma.
      CONCLUSION: The unadjusted findings suggest that distance to pharmacies may play
      a role in the pharmaceutical management of asthma, though these findings are
      explained by confounding factors. Future research should continue to explore the
      effect of spatial access to pharmacies on chronic disease management and the role
      that maps can play in guiding medication management interventions in a larger
      sample to allow for more rigorous analysis.

PMID- 30279129
TI  - Validation of a risk stratification tool for a Hospital Outreach Medication
      Review (HOMR) program.
AB  - BACKGROUND: Early hospital readmissions are a challenging and costly experience
      for both patients and the healthcare service. Reducing hospital readmission rates
      is a priority for health services globally and this is evident with the
      establishment of multiple outpatient services to promote early follow-up and to
      initiate secondary preventative care measures. One such intervention has been the
      introduction of a pharmacist-led, Hospital Outreach Medication Review (HOMR)
      service. However, the demand for the service has meant reaching this target has
      become an increasingly ambitious goal within allocated resources. OBJECTIVE: To
      validate a risk-stratification tool to identify low-risk patients in whom a
      telephone medication review would be a safe and effective alternative to a home
      based review. METHOD: A risk tool was derived and applied to a retrospective
      sample to act as the parent cohort. A prospective cohort was stratified into low
      and high-risk based on this tool, and received either a telephone or a
      traditional home medication review respectively. RESULTS: 235 patients were
      included in final analysis (n = 113 prospective, n = 122 baseline controls). High
      risk patients were more likely to be readmitted at 60 and 90 days in the baseline
      cohort (9/38 vs 7/84, p = 0.04 and 11/38 vs 9/84, p = 0.02 respectively), with a
      trend towards increased readmissions at 30 days (5/38 vs 3/84, p = 0.11).
      Logistic regression identified the risk tool as an independent predictor of
      hospital readmission (IRR 1.18, p = 0.04), whereas age and Charlson comorbidity
      were not (p = 0.80 and 0.31 respectively). There was no significant difference
      between the new model (incorporating phone reviews) and the parent cohort (p =
      0.25). CONCLUSION: Our risk score was able to identify those at highest risk of
      hospital readmission at 60 and 90 days. Utilising this risk score, a telephone
      HOMR for low-risk patients was a safe and efficient alternative to a traditional
      home review.

PMID- 30279130
TI  - Medication prior authorization from the providers perspective: A prospective
      observational study.
AB  - BACKGROUND: The prior authorization (PA) process for medications used by
      community providers requires modernization. Therefore, a deeper understanding of
      current state of PA from the community provider perspective is imperative to
      inform and modernize this managed care tool. OBJECTIVES: Objectives of this study
      were to identify, analyze and categorize the issues associated with the
      medication PA process from provider practice perspective. METHODS: A prospective
      non-experimental, cross sectional, observational study was performed using semi
      structured interviews and direct observation at a convenience sample of eight
      primary care and medicine subspecialty group practices in Tucson, Arizona, USA.
      Participating practices were required to have an established medication PA
      process. The participant feedback from each site was analyzed using the Richards
      qualitative coding technique that includes descriptive coding, topic coding, and
      analytical coding. RESULTS: Data were obtained from eight unique community
      provider offices (8 sites) at which 29 prescribers practice. The pain points
      identified represented five main categories: 1) information transfer gaps; 2)
      format disparities; 3) outdated technologies; 4) care consequences; and 5)
      workarounds. Prescribers and their staff suggested improvements that included
      real time eligibility and formulary alerts regarding PA during the e-prescribing
      process, accurate, up-to-date formulary data with easy-to-access alternatives,
      and embedded PA that is integrated with electronic medical record data. Three
      sites used medication PA portals such as CoverMyMeds(r) for information
      gathering, but at the time of data collection, no sites used these PA portals for
      prospective electronic prior authorization (ePA) or the electronic process of
      requesting authorization from health plan payers for coverage. CONCLUSION: The PA
      process for medication used by community providers is in urgent need of
      modernization. Pain points identified in this study could be alleviated by
      implementing medication ePA solutions. However, providers and their staff are
      largely unaware that ePA exists. Additional research in this area is needed.

PMID- 30279131
TI  - Community pharmacy interventions to improve antibiotic stewardship and
      implications for pharmacy education: A narrative overview.
AB  - BACKGROUND: Antibiotic resistance is one of the world's most pressing public
      health problems, resulting in over 23,000 deaths per year. One of the main
      contributing factors to antimicrobial resistance is antibiotic misuse and
      overuse. Community pharmacists can play a role in reducing antibiotic resistance,
      since they are one of the most accessible healthcare professionals. OBJECTIVE:
      The purpose of this paper is to describe community pharmacy interventions and
      strategies to reduce antibiotic misuse and overuse and to discuss the
      implications for pharmacy training. METHODS: A narrative overview strategy was
      employed to identify papers on antibiotic stewardship and the role of the
      community pharmacist. Our review examined potential stewardship strategies and
      interventions within community pharmacy practice that provide opportunities for
      pharmacists to engage or lead in the reduction of antimicrobial resistance.
      RESULTS: We describe five promising community pharmacist-led intervention
      strategies: Collaborative Practice Agreements (CPAs), point-of-care (POC)
      testing, patient consultations, academic detailing and serving as an advocate for
      patients and other healthcare providers CONCLUSIONS: This review highlights
      topics that may warrant increased attention in pharmacy school curricula.
      Pharmacy schools may want to consider modifying their curricula to address the
      shifts in practice of the community pharmacist - emphasizing the expanded role of
      the pharmacist in patient care and public health issues such as outpatient
      antibiotic stewardship.

PMID- 30279132
TI  - Japanese orthopaedic association cervical myelopathy evaluation questionnaire
      (JOACMEQ): Part 5. Determination of responsiveness.
AB  - BACKGROUND: In 1999, the Japanese Orthopaedic Association decided to develop a
      new Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). The final version of
      the JOACMEQ, comprising 24 questions and five domains (cervical spine function
      (CF); upper extremity function (UF); lower extremity function (LF); bladder
      function (BF); and quality of life (QOL)), was established after three nationwide
      investigations. The fourth investigation, reported in this paper, was performed
      to confirm the responsiveness of the questionnaire. METHODS: A total of 137
      patients with cervical myelopathy were included in the study. Each patient was
      interviewed twice using the JOACMEQ before and after treatment. At the second
      interview, the patients self-rated their condition in five domains for "worse,"
      "somewhat worse," "no change," "somewhat better," or "better," and these scores
      were defined as the external assessment rating. The difference of the points in
      five domains between the first and the second interview was calculated against
      each external assessment. Based on the results, substantial clinical benefit
      (SCB) thresholds for the JOACMEQ were determined. RESULTS: The statistically
      significant median values of the acquired points were 17.5 for CF, 16.0 and 21.0
      for UF, 27.0 and 20.5 for LF, 13.0 for BF, and 29.0 for QOL. After consideration
      of the results, the committee decided that an acquired point >=20 could be
      interpreted as representing an SCB threshold for the JOACMEQ. CONCLUSION: We have
      concluded that a treatment can be judged to be effective for a patient if 1) The
      patient give all answers for the questions necessary to calculate the functional
      score of a domain and an increase of >=20 points is obtained for that score, or
      2) The functional score after treatment is > 90 points even if the answer for the
      unanswered questions was supposed to be the worst possible choice.

PMID- 30279133
TI  - Dose optimization of topical tranexamic acid for primary total hip arthroplasty:
      A prospective cohort study.
AB  - BACKGROUND: Recently, the topical application of tranexamic acid has become
      widespread, and it is effective in reducing postoperative blood loss and
      transfusion rate in total hip arthroplasty. There is no consensus on the optimal
      dose of topical tranexamic acid. This study aimed to assess the efficacy and
      safety of topical tranexamic acid on postoperative blood loss and determine the
      optimal topical dose for primary total hip arthroplasty. METHODS: This
      prospective cohort study with a robust protocol enrolled 79 patients who received
      either 1 or 2 g of topical tranexamic acid in 30 mL normal saline solution or an
      equivalent volume of normal saline at the end of surgery. The primary outcomes
      were postoperative drain blood loss and hemoglobin decrease on postoperative day
      7. The secondary outcomes were transfusion rate, d-dimer level on postoperative
      day 7, symptomatic deep vein thrombosis rate, and duration of hospital stay.
      RESULTS: Both 1 and 2 g tranexamic acid significantly reduced postoperative drain
      blood loss (p < 0.001). These doses also reduced the hemoglobin concentration
      decrease on postoperative day 7, but not significantly. Furthermore, 1 and 2 g
      doses of tranexamic acid had similar effects on postoperative blood loss and
      hemoglobin concentration decrease. There was no difference in the transfusion
      rate, d-dimer level, symptomatic deep vein thrombosis rate, and length of
      hospital stay. CONCLUSIONS: The use of topical tranexamic acid at the end of
      surgery is effective and safe for reducing postoperative blood loss in primary
      total hip arthroplasty. Topical tranexamic acid at a dose of 1 g may be
      sufficient and cost-effective, with fewer side effects than the higher dose.

PMID- 30279134
TI  - Anatomical analysis of the human ligamentum flavum in the thoracic spine:
      Clinical implications for posterior thoracic spinal surgery.
AB  - BACKGROUND: Knowledge of the ligamentum flavum anatomy is important for posterior
      spinal surgery. However, only a few studies have evaluated the relationship
      between the thoracic ligamentum flavum and its surrounding structures. This study
      aimed to clarify the anatomy of the thoracic ligamentum flavum. METHODS: The
      entire spines from 20 human embalmed cadavers were harvested in an en bloc
      fashion. All pedicles were vertically cut using a thread bone saw, and the
      ligamentum flavum from T1-T2 to T12-L1 was painted using a contrast agent
      containing an iron powder. Computed tomography was performed, and the ligamentum
      flavum shape (width and height) and its relationship with the spinal bony
      structures (lamina and foramen height percentage covered by the ligamentum
      flavum) were analyzed using a three-dimensional analyzing software. RESULTS: The
      thoracic ligamentum flavum height and width gradually increased from T1-T2 to T12
      L1. The caudal lamina height ventrally covered by the ligamentum flavum also
      increased gradually from the upper (T1-T2: 31.7%) to the lower levels (T12-L1:
      41.7%); however, the cranial lamina height dorsally covered by the ligamentum
      flavum decreased from the upper (12.6%) to the lower levels (4.3%). The neural
      foramen was covered by the ligamentum flavum in all thoracic spines, except for
      T1-T2. Between T2-T3 and T12-L1, approximately 50% of the cranial part of the
      foramens was covered by the ligamentum flavum; however, the caudal part was not
      covered. CONCLUSIONS: This study using contrasted ligamentum flavum and
      reconstructed CT provided information on the thoracic ligamentum flavum shape and
      its relationship with the bony structures. The ventral ligamentum flavum coverage
      of the cranial lamina increase from cranial to caudal, and the cranial half of
      the neural foramen is covered by the ligamentum flavum below T2-T3 but not in T1
      T2. These findings would help spine surgeons to design and perform safe and
      adequate posterior thoracic spinal surgeries.

PMID- 30279135
TI  - Is metatarsus primus elevatus truly observed in hallux rigidus? Radiographic
      study using mapping methods.
AB  - BACKGROUND: Hallux rigidus and metatarsus primus elevatus (MPE) are associated,
      but their causal relationship remains unknown. Several surgical approaches for
      treating hallux rigidus are available. We evaluated morphological characteristics
      of hallux rigidus with different grades to determine the optimal surgical
      approach. The amount of degenerative change in the metatarsophalangeal joint on
      the preoperative roentgenograms was graded on a scale of 1-3. We analyzed the
      morphology of hallux rigidus using X-ray image mapping developed by our team.
      METHODS: This study involved weight-bearing, dorsoplantar, and lateral foot X
      rays of 36 feet from 26 patients underwent surgery for hallux rigidus (Group R)
      at our institution, and 26 normal feet (Group N). A two-dimensional coordinate
      system was used to analyze the sharps of these feet by converting each dot on the
      radiographs into X and Y coordinates. Diagrams of the feet from each group were
      drawn for comparison. Feet with grades 2 (Group R2) and 3 (Group R3) hallux
      rigidus and normal feet were compared by Kruskal-Wallis test. RESULTS: Mapping
      revealed that the tip of distal phalanges of the second, and third toes in Group
      R medially shifted (P < 0.05) in dorsoplantar image of the feet, and that the
      medial point, a part of the talus, navicular, cuneiform, and first metatarsal
      bone in Group R, shifted lower (P < 0.05) in lateral feet images of the feet.
      Multiple comparisons revealed a significant navicular bone depression in grade 3
      hallux rigidus compared with normal feet. A significant difference was observed
      between Group N and R3 but not between Group R2 and N or R3. CONCLUSIONS: X-ray
      morphological analysis of the foot revealed MPE in Group R. Elevation gradually
      increased as hallux rigidus grade worsened. Therefore, osteotomy combined with
      cheilectomy, whereby the first metatarsal bone can be tilted toward the plantar
      side, are useful for treating a higher-grade hallux rigidus. LEVEL OF EVIDENCE:
      Level III, comparative study.

PMID- 30279137
TI  - Creating a Rural Surgery Track and a Review of Rural Surgery Training Programs.
AB  - OBJECTIVE: The objective of this study was to present the process of developing a
      rural surgery training track within an established residency program and review
      the current rural surgery training programs in the nation. DESIGN: This study
      reviews current rural surgery training opportunities at Accreditation Council for
      Graduate Medical Education accredited surgical residencies in the United States
      and presents the process of creating the University of Minnesota's rural surgery
      training track. SETTING: This study was performed at the University of Minnesota,
      in Minneapolis, Minnesota, and at Essentia Health-Saint Mary's Medical Center, in
      Duluth, Minnesota. PARTICIPANTS: Accredited general surgery residencies were
      reviewed. The creation of a designated rural surgery training track added an
      additional rural-designated surgical resident during each postgraduation year and
      created a required postgraduation year 2 rural surgery rotation for all
      categorical surgical residents. RESULTS: Two hundred sixty-eight surgery
      residency programs were reviewed. Twenty-seven had required rural rotations, 10
      offered only elective rural rotations, and 4 had dedicated National Resident
      Matching Program codes for rural training tracks. After review of national rural
      surgery training opportunities, the University of Minnesota's process of creating
      a designated rural surgery training program required attention to 5 main
      components: needs assessment and review of local opportunities, surgery residency
      review committee approval, funding, surgical education, and clinical/operative
      education. CONCLUSIONS: Increasing opportunities for surgical residents to train
      in rural settings may help with recruitment of medical students and retention of
      surgeons pursuing careers in rural surgery.

PMID- 30279138
TI  - Involvement of released sphingosine 1-phosphate/sphingosine 1-phosphate receptor
      axis in skeletal muscle atrophy.
AB  - Skeletal muscle (SkM) atrophy is caused by several and heterogeneous conditions,
      such as cancer, neuromuscular disorders and aging. In most types of SkM atrophy
      overall rates of protein synthesis are suppressed, protein degradation is
      consistently elevated and atrogenes, such as the ubiquitin ligase Atrogin
      1/MAFbx, are up-regulated. The molecular regulators of SkM waste are multiple and
      only in part known. Sphingolipids represent a class of bioactive molecules
      capable of modulating the destiny of many cell types, including SkM cells. In
      particular, we and others have shown that sphingosine 1phosphate (S1P), formed by
      sphingosine kinase (SphK), is able to act as trophic and morphogenic factor in
      myoblasts. Here, we report the first evidence that the atrophic phenotype
      observed in both muscle obtained from mice bearing the C26 adenocarcinoma and
      C2C12 myotubes treated with dexamethasone was characterized by reduced levels of
      active phospho-SphK1. The importance of SphK1 activity is also confirmed by the
      specific pharmacological inhibition of SphK1 able to increase Atrogin-1/MAFbx
      expression and reduce myotube size and myonuclei number. Furthermore, we found
      that SkM atrophy was accomplished by significant increase of S1P transporter
      Spns2 and in changes in the pattern of S1P receptor (S1PRs) subtype expression
      paralleled by increased Atrogin-1/MAFbx expression, suggesting a role for the
      released S1P and of specific S1PR-mediated signaling pathways in the control of
      the ubiquitin ligase. Altogether, these findings provide the first evidence that
      SphK1/released S1P/S1PR axis acts as a molecular regulator of SkM atrophy,
      thereby representing a new possible target for therapy in many patho
      physiological conditions.

PMID- 30279136
TI  - Decoding Cognitive Processes from Neural Ensembles.
AB  - An intrinsic difficulty in studying cognitive processes is that they are
      unobservable states that exist in between observable responses to the sensory
      environment. Cognitive states must be inferred from indirect behavioral measures.
      Neuroscience potentially provides the tools necessary to measure cognitive
      processes directly, but it is challenged on two fronts. First, neuroscientific
      measures often lack the spatiotemporal resolution to identify the neural
      computations that underlie a cognitive process. Second, the activity of a single
      neuron, which is the fundamental building block of neural computation, is too
      noisy to provide accurate measurements of a cognitive process. In this paper, I
      examine recent developments in neurophysiological recording and analysis methods
      that provide a potential solution to these problems.

PMID- 30279139
TI  - Mechanistic targeting of advanced glycation end-products in age-related diseases.
AB  - Glycative stress, caused by the accumulation of cytotoxic and irreversibly-formed
      sugar-derived advanced glycation end-products (AGEs), contributes to morbidity
      associated with aging, age-related diseases, and metabolic diseases. In this
      review, we summarize pathways leading to formation of AGEs, largely from sugars
      and glycolytic intermediates, and discuss detoxification of AGE precursors,
      including the glyoxalase system and DJ-1/Park7 deglycase. Disease pathogenesis
      downstream of AGE accumulation can be cell autonomous due to aggregation of
      glycated proteins and impaired protein function, which occurs in ocular
      cataracts. Extracellular AGEs also activate RAGE signaling, leading to oxidative
      stress, inflammation, and leukostasis in diabetic complications such as diabetic
      retinopathy. Pharmaceutical agents have been tested in animal models and
      clinically to diminish glycative burden. We summarize existing strategies and
      point out several new directions to diminish glycative stress including: plant
      derived polyphenols as AGE inhibitors and glyoxalase inducers; improved dietary
      patterns, particularly Mediterranean and low glycemic diets; and enhancing
      proteolytic capacities of the ubiquitin-proteasome and autophagy pathways that
      are involved in cellular clearing of AGEs.

PMID- 30279140
TI  - The GDF11-FTO-PPARgamma axis controls the shift of osteoporotic MSC fate to
      adipocyte and inhibits bone formation during osteoporosis.
AB  - During osteoporosis, the shift of bone mesenchymal stem cell (BMSC) lineage
      commitment to adipocyte leads to the imbalance between bone mass and fat, which
      increases the risk of fracture. The mechanism underlying this process is not
      fully understood. Fat mass and obesity-associated protein (FTO) is an RNA
      demethylase that demethylates various methylated nucleic acids and participates
      in various physiological and pathological processes. Here we identified FTO as a
      regulator for BMSC fate determination during osteoporosis. FTO was up-regulated
      in bone marrow during aging or osteoporosis in human and mice in a GDF11(growth
      differentiation factor 11)-C/EBPalpha-dependent mechanism. The expression of FTO
      was also up-regulated during adipocyte differentiation of BMSCs whereas its
      expression was down-regulated during osteoblast differentiation. Gain-of-function
      and loss-of-function experiments showed that FTO favored the BMSCs to
      differentiate to adipocytes rather than osteoblasts. Further mechanism study
      demonstrated that FTO bound and demethylated the mRNA of the Peroxisome
      proliferator-activated receptor gamma (Pparg), leading to the increase in the
      expression of Pparg mRNA. Reversely, Pparg knockdown blocked the function of
      GDF11-FTO during osteoblast differentiation of BMSCs. Furthermore, conditionally
      genetic knockout of Fto in osteoblasts inhibited the development of osteopenia in
      mice. Collectively, our findings demonstrated that GDF11-FTO-Pparg axis promoted
      the shift of osteoporotic BMSC fate to adipocyte and inhibited bone formation
      during osteoporosis.

PMID- 30279142
TI  - Corrigendum to "Dynamic assessment of tau immunotherapies in the brains of live
      animals by two-photon imaging" EBioMedicine 35 (2018) 270-278.

PMID- 30279141
TI  - Human rhomboid family-1 modulates clathrin coated vesicle-dependent pro
      transforming growth factor alpha membrane trafficking to promote breast cancer
      progression.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) signalling is critical in
      epithelial cancer development. Human rhomboid family-1 (RHBDF1) facilitates the
      secretion of TGFalpha, an EGFR ligand, in breast cancer; however, the underlying
      mechanism remains unclear. We evaluated the role for RHBDF1 in clathrin-coated
      vesicle (CCV)-dependent pro-TGFalpha membrane trafficking in breast cancer cells
      upon stimulation by G-protein coupled receptor (GPCR) agonists. METHODS: RHBDF1
      was silenced in various breast cancer cells using shRNA. TGFalpha levels,
      subcellular localization, and secretion were evaluated using ELISA,
      immunofluorescent staining, and coimmunoprecipitation. Phosphorylation and
      expression of relevant proteins were measured by western blotting. RHBDF1
      dependent cell viability and invasion were measured. FINDINGS: RHBDF1 mediates
      GPCR agonist-induced EGFR phosphorylation by promoting TGFalpha secretion in
      various types of breast cancer cells. RHBDF1 not only mediates ADAM17-dependent
      shedding of TGFalpha, but is essential in membrane trafficking of pro-TGFalpha.
      RHBDF1 silencing results in blocking of clathrin uncoating from CCV, a crucial
      step for the plasma membrane release of pro-TGFalpha. Interaction of RHBDF1 with
      auxilin-2, a CCV protein, determines the recruitment of HSC70 to CCV to
      facilitate clathrin uncoating. RHBDF1 function is required for the proliferation
      and mobility of breast cancer cells upon stimulation by Sphingosine 1 Phosphate
      (S1P), a GPCR agonist. We demonstrate a significant correlation between RHBDF1
      overexpression and EGFR activation in breast cancer tissues. INTERPRETATION:
      RHBDF1 is an indispensable component of the protein trafficking machinery
      involved in GPCR-mediated EGFR transactivation, and is an attractive therapeutic
      target for cancer. FUND: National Natural Science Foundation of China (81,672,740
      to ZSZ, 81,272,356 and 81,330,029 to LYL).

PMID- 30279145
TI  - Detection and quantitation of iron in ferritin, transferrin and labile iron pool
      (LIP) in cardiomyocytes using 55Fe and storage phosphorimaging.
AB  - Dysregulated iron metabolism has a detrimental effect on cardiac function. The
      importance of iron homeostasis in cardiac health and disease warrants detailed
      studies of cardiomyocyte iron uptake, utilization and recycling at the molecular
      level. In this study, we have performed metabolic labeling of primary cultures of
      neonatal rat cardiomyocytes with radioactive iron coupled with separation of
      labeled iron-containing molecules by native electrophoresis followed by detection
      and quantification of incorporated radioiron by storage phosphorimaging. For the
      radiolabeling we used a safe and convenient beta emitter 55Fe which enabled
      sensitive and simultaneous detection and quantitation of iron in cardiomyocyte
      ferritin, transferrin and the labile iron pool (LIP). The LIP is believed to
      represent potentially dangerous redox-active iron bound to uncharacterized
      molecules. Using size-exclusion chromatography spin micro columns, we demonstrate
      that iron in the LIP is bound to high molecular weight molecule(s) (>=5000 Da) in
      the neonatal cardiomyocytes.

PMID- 30279144
TI  - SIRT5 deacylates metabolism-related proteins and attenuates hepatic steatosis in
      ob/ob mice.
AB  - BACKGROUND: Sirtuin 5 (SIRT5) is a NAD+-dependent lysine deacylase. The SIRT5
      deficiency mouse model shows that it is dispensable for metabolic homeostasis
      under normal conditions. However, the biological role of SIRT5 and acylation in
      pathological states such as obesity and type 2 diabetes (T2D) remains elusive.
      METHODS: The hepatic SIRT5-overexpressing ob/ob mouse model (ob/ob-SIRT5 OE) was
      established by CRISPR/Cas9 gene editing tool Protein malonylation and
      succinylation lysine sites were identified by immunoprecipitation coupled lipid
      chromatography - tandem mass spectrometry (LC-MS/MS) methods. FINDINGS: The ob/ob
      SIRT5 OE mice showed decreased malonylation and succinylation, improved cellular
      glycolysis, suppressed gluconeogenesis, enhanced fatty acid oxidation, and
      attenuated hepatic steatosis. A total of 955 malonylation sites on 434 proteins
      and 1377 succinylation sites on 429 proteins were identified and quantitated.
      Bioinformatics analysis revealed that malonylation was the major SIRT5 target in
      the glycolysis/gluconeogenesis pathway, whereas succinylation was the preferred
      SIRT5 target in the oxidative phosphorylation pathway. INTERPRETATION: Hepatic
      overexpression of SIRT5 ameliorated the metabolic abnormalities of ob/ob mice,
      probably through demalonylating and desuccinylating proteins in the main
      metabolic pathways. SIRT5 and related acylation might be potential targets for
      metabolic disorders. FUND: National Key R&D Program of China, the National
      Natural Science Foundation of China, the Strategic Priority Research Programs
      (Category A) of the Chinese Academy of Sciences, the Interdisciplinary Medicine
      Seed Fund of Peking University and the National Laboratory of Biomacromolecules.

PMID- 30279147
TI  - Genetically encoded fluorescent indicators for live cell pH imaging.
AB  - BACKGROUND: Intracellular pH underlies most cellular processes. There is emerging
      evidence of a pH-signaling role in plant cells and microorganisms. Dysregulation
      of pH is associated with human diseases, such as cancer and Alzheimer's disease.
      SCOPE OF REVIEW: In this review, we attempt to provide a summary of the progress
      that has been made in the field during the past two decades. First, we present an
      overview of the current state of the design and applications of fluorescent
      protein (FP)-based pH indicators. Then, we turn our attention to the development
      and applications of hybrid pH sensors that combine the capabilities of non-GFP
      fluorophores with the advantages of genetically encoded tags. Finally, we discuss
      recent advances in multicolor pH imaging and the applications of genetically
      encoded pH sensors in multiparameter imaging. MAJOR CONCLUSIONS: Genetically
      encoded pH sensors have proven to be indispensable noninvasive tools for
      selective targeting to different cellular locations. Although a variety of
      genetically encoded pH sensors have been designed and applied at the single cell
      level, there is still much room for improvements and future developments of novel
      powerful tools for pH imaging. Among the most pressing challenges in this area is
      the design of brighter redshifted sensors for tissue research and whole animal
      experiments. GENERAL SIGNIFICANCE: The design of precise pH measuring instruments
      is one of the important goals in cell biochemistry and may give rise to the
      development of new powerful diagnostic tools for various diseases.

PMID- 30279146
TI  - Dependence of HSP27 cellular level on protein kinase CK2 discloses novel
      therapeutic strategies.
AB  - BACKGROUND: HSP27 plays a role in various diseases, including neurodegenerative
      diseases, ischemia, and atherosclerosis. It is particularly important in the
      regulation of the development, progression and metastasis of cancer as well as
      cell apoptosis and drug resistance. However, the absence of an ATP binding
      domain, that is, instead, present in other HSPs such as HSP90 and HSP70, hampers
      the development of small molecules as inhibitors of HSP27. METHODS: Knockout cell
      lines generated by Crispr/Cas9 gene editing tool, specific kinase inhibitors and
      siRNA transfections were exploited to demonstrate that the expression of HSP27 is
      dependent on the integrity/activity of protein kinase CK2 holoenzyme. The
      interaction between these proteins has been confirmed by co-immunoprecipitation,
      confocal immunofluorescence microscopy, and by density gradient separation of
      protein complexes. Finally, using a proliferation assay this study demonstrates
      the potential efficacy of a combinatory therapy of heath shock and CK2 inhibitors
      in cancer treatment. RESULTS: Our data demonstrate that CK2 is able to regulate
      HSP27 turnover by affecting the expression of its ubiquitin ligase SMURF2 (Smad
      ubiquitination regulatory factor 2). Moreover, for the first time we show an
      increased sensitivity of CK2-inhibited tumour cells to hyperthermia treatment.
      CONCLUSION: Being HSP27 involved in several pathological conditions, including
      protein conformational diseases (i.e Cystic Fibrosis) and cancer, the need of
      drugs to modulate its activity is growing and CK2-targeting could represent a new
      strategy to reduce cellular HSP27 level. GENERAL SIGNIFICANCE: This study
      identifies CK2 as a molecular target to control HSP27 cellular expression.

PMID- 30279143
TI  - Fisetin is a senotherapeutic that extends health and lifespan.
AB  - BACKGROUND: Senescence is a tumor suppressor mechanism activated in stressed
      cells to prevent replication of damaged DNA. Senescent cells have been
      demonstrated to play a causal role in driving aging and age-related diseases
      using genetic and pharmacologic approaches. We previously demonstrated that the
      combination of dasatinib and the flavonoid quercetin is a potent senolytic
      improving numerous age-related conditions including frailty, osteoporosis and
      cardiovascular disease. The goal of this study was to identify flavonoids with
      more potent senolytic activity. METHODS: A panel of flavonoid polyphenols was
      screened for senolytic activity using senescent murine and human fibroblasts,
      driven by oxidative and genotoxic stress, respectively. The top senotherapeutic
      flavonoid was tested in mice modeling a progeroid syndrome carrying a p16INK4a
      luciferase reporter and aged wild-type mice to determine the effects of fisetin
      on senescence markers, age-related histopathology, disease markers, health span
      and lifespan. Human adipose tissue explants were used to determine if results
      translated. FINDINGS: Of the 10 flavonoids tested, fisetin was the most potent
      senolytic. Acute or intermittent treatment of progeroid and old mice with fisetin
      reduced senescence markers in multiple tissues, consistent with a hit-and-run
      senolytic mechanism. Fisetin reduced senescence in a subset of cells in murine
      and human adipose tissue, demonstrating cell-type specificity. Administration of
      fisetin to wild-type mice late in life restored tissue homeostasis, reduced age
      related pathology, and extended median and maximum lifespan. INTERPRETATION: The
      natural product fisetin has senotherapeutic activity in mice and in human
      tissues. Late life intervention was sufficient to yield a potent health benefit.
      These characteristics suggest the feasibility to translation to human clinical
      studies. FUND: NIH grants P01 AG043376 (PDR, LJN), U19 AG056278 (PDR, LJN, WLL),
      R24 AG047115 (WLL), R37 AG013925 (JLK), R21 AG047984 (JLK), P30 DK050456
      (Adipocyte Subcore, JLK), a Glenn Foundation/American Federation for Aging
      Research (AFAR) BIG Award (JLK), Glenn/AFAR (LJN, CEB), the Ted Nash Long Life
      and Noaber Foundations (JLK), the Connor Group (JLK), Robert J. and Theresa W.
      Ryan (JLK), and a Minnesota Partnership Grant (AMAY-UMN#99)-P004610401-1 (JLK,
      EAA).

PMID- 30279149
TI  - Quantifying codon usage in signal peptides: Gene expression and amino acid usage
      explain apparent selection for inefficient codons.
AB  - The Sec secretion pathway is found across all domains of life. A critical feature
      of Sec secreted proteins is the signal peptide, a short peptide with distinct
      physicochemical properties located at the N-terminus of the protein. Previous
      work indicates signal peptides are biased towards translationally inefficient
      codons, which is hypothesized to be an adaptation driven by selection to improve
      the efficacy and efficiency of the protein secretion mechanisms. We investigate
      codon usage in the signal peptides of E. coli using the Codon Adaptation Index
      (CAI), the tRNA Adaptation Index (tAI), and the ribosomal overhead cost
      formulation of the stochastic evolutionary model of protein production rates (ROC
      SEMPPR). Comparisons between signal peptides and 5'-end of cytoplasmic proteins
      using CAI and tAI are consistent with a preference for inefficient codons in
      signal peptides. Simulations reveal these differences are due to amino acid usage
      and gene expression - we find these differences disappear when accounting for
      both factors. In contrast, ROC-SEMPPR, a mechanistic population genetics model
      capable of separating the effects of selection and mutation bias, shows codon
      usage bias (CUB) of the signal peptides is indistinguishable from the 5'-ends of
      cytoplasmic proteins. Additionally, we find CUB at the 5'-ends is weaker than
      later segments of the gene. Results illustrate the value in using models grounded
      in population genetics to interpret genetic data. We show failure to account for
      mutation bias and the effects of gene expression on the efficacy of selection
      against translation inefficiency can lead to a misinterpretation of codon usage
      patterns.

PMID- 30279148
TI  - Myrtenal-induced V-ATPase inhibition - A toxicity mechanism behind tumor cell
      death and suppressed migration and invasion in melanoma.
AB  - BACKGROUND: Metastatic tumor cells have acidic extracellular pH and differential
      electrochemical H+ gradients generated across their cell membranes by V-type H+
      ATPases. This study shows that inhibition of the V-ATPases by the plant-derived
      monoterpene Myrtenal results in tumor cell death and decreased metastatic
      dissemination in mice. METHODS: The Myrtenal anticancer toxicity was evaluated in
      vitro using murine (B16F0 and B16F10) and human (SkMel-5) melanoma cell lines,
      and in in vivo mouse metastatic dissemination model. Proton flux and
      extracellular acidification were directly evaluated at the surface of living
      cells using a non-invasive selective ion electrode approach. RESULTS: The
      inhibition of V-ATPases by 100 MUM Myrtenal disrupted the electrochemical H+
      gradient across the cell membranes, strongly induced cell death (4-5 fold), and
      decreased tumor cells migration and invasion in vitro. Myrtenal (15 mg/kg) also
      significantly reduced metastasis induced by B16F10 in vivo, further reinforcing
      that V-ATPase is a molecular target to halt the progression of cancers.
      CONCLUSIONS: These data revealed the therapeutic potential of Myrtenal as
      inhibitor of melanoma progression proposing a mechanism of action by which once
      inhibited by this monoterpene the proton pumps fail to activate cancer-related
      differential electrochemical gradients and H+ fluxes across the tumor cell
      membranes, disrupting pH signatures inherent in tumor progression, resulting in
      reprogrammed cell death and metastasis inhibition. GENERAL SIGNIFICANCE: The work
      represents a new mechanistic strategy for contention of melanoma, the most
      aggressive and deadly form of cutaneous neoplasm, and highlights Myrtenal, other
      related monoterpenes and derivatives as promising proton pump inhibitors with
      high chemotherapeutic potential.

PMID- 30279150
TI  - Probing the effect of membrane contents on transmembrane protein-protein
      interaction using solution NMR and computer simulations.
AB  - The interaction between the secondary structure elements is the key process,
      determining the spatial structure and activity of a membrane protein.
      Transmembrane (TM) helix-helix interaction is known to be especially important
      for the function of so-called type I or bitopic membrane proteins. In the present
      work, we present the approach to study the helix-helix interaction in the TM
      domains of membrane proteins in various lipid environment using solution NMR
      spectroscopy and phospholipid bicelles. The technique is based on the ability of
      bicelles to form particles with the size, depending on the lipid/detergent ratio.
      To implement the approach, we report the experimental parameters of "ideal
      bicelle" models for four kinds of zwitterionic phospholipids, which can be also
      used in other structural studies. We show that size of bicelles and type of the
      rim-forming detergent do not affect substantially the spatial structure and
      stability of the model TM dimer. On the other hand, the effect of bilayer
      thickness on the free energy of the dimer is dramatic, while the structure of the
      protein is unchanged in various lipids with fatty chains having a length from 12
      to 18 carbon atoms. The obtained data is analyzed using the computer simulations
      to find the physical origin of the observed effects.

PMID- 30279152
TI  - Antimicrobial peptides from C-terminal amphipathic region of E. coli FtsA.
AB  - Antimicrobial peptides constitute an indispensable component of innate immune
      system in organisms ranging from bacteria to man. Despite this, peptides lag far
      behind the conventional antibiotics in treating infections. The menace of
      multidrug-resistant bacteria, however, has revived the antimicrobial peptide
      research. We reasoned that the membrane-binding regions of bacterial proteins
      could be purposed to combat them. Here, we identify potent antimicrobial peptides
      from the C-terminal amphipathic helix of E. coli FtsA protein. The 11 and 13
      residue peptides exhibited activity against E. coli, gentamicin-resistant MRSA,
      and C. albicans. The activity is little affected by the presence of salt and
      divalent cations. The peptides preferentially bind to the negatively-charged
      membranes as indicated by tryptophan fluorescence studies. The peptides
      permeabilize the E. coli outer and inner membranes at very promising
      concentrations suggesting membrane-disruption as one of the mechanisms of
      killing.

PMID- 30279151
TI  - Intercellular communication via gap junction channels between chondrocytes and
      bone cells.
AB  - Cell-to-cell communication between bone, cartilage and the synovial membrane is
      not fully understood and it is only attributed to the diffusion of substances
      through the extracellular space or synovial fluid. In this study, we found for
      the first time that primary bone cells (BCs) including osteocytes, synovial cells
      (SCs) and chondrocytes (CHs) are able to establish cellular contacts and to
      couple through gap junction (GJ) channels with connexin43 (Cx43) being dominant.
      Transwell co-culture and identification by mass spectrometry revealed the
      exchange of essential amino acids, peptides and proteins including calnexin,
      calreticulin or CD44 antigen between contacting SCs, BCs and CHs. These results
      reveal that CHs, SCs and BCs are able to establish intercellular connections and
      to communicate through GJ channels, which provide a selective signalling route by
      the direct exchange of potent signalling molecules and metabolites.

PMID- 30279153
TI  - Transmission of IMI-2 carbapenemase-producing Enterobacteriaceae from river water
      to human.
AB  - OBJECTIVES: Carbapenemase-producing Enterobacteriaceae (CPE) are increasing
      worldwide in human infections. The role of rivers as reservoirs is highlighted,
      but transmission from the environment to humans is not documented. A human case
      of bacteraemia caused by IMI-2 carbapenemase-producing Enterobacter asburiae
      following massive river water exposure underwent microbiological investigations
      with the aim of deciphering the origin and mechanism of infection. METHODS:
      Clinical and environmental bacterial strains were compared by resistotyping and
      genomotyping using pulsed-field gel electrophoresis (PFGE). PFGE was also used to
      determine the location of the blaIMI-2 carbapenemase gene. The patient's
      microbiota and river bacterial communities were compared by fingerprinting using
      16S rRNA gene PCR-temporal temperature gel electrophoresis. RESULTS: Enterobacter
      asburiae causing bacteraemia carried the same plasmidic blaIMI-2 gene as E.
      asburiae strains detected in river water 1 month later. Clinical and river
      strains displayed identical PFGE profiles. Community fingerprinting showed the
      persistence in the patient's microbiota of carbapenem-resistant bacteria, which
      were also autochthonous in the river community (E. asburiae, Aeromonas veronii
      and Pseudomonas fluorescens). CONCLUSION: Here we have identified for the first
      time the presence of an IMI-2-producing E. asburiae in a river in the South of
      France and suggest transmission from the river to a human probably following
      intestinal translocation. General insights into transmission of CPE from the
      environment to humans are gained from this case. Considering the rapid spread of
      CPE in humans, the risk of transfer from an environmental reservoir to human
      microbiota should be thoroughly investigated at least by implementing
      environmental surveillance of carbapenem resistance.

PMID- 30279154
TI  - Supported Internet-Delivered Cognitive Behavior Treatment for Adults with Severe
      Depressive Symptoms: A Secondary Analysis.
AB  - BACKGROUND: Depression is a highly prevalent mental health issue that exacts
      significant economic, societal, personal, and interpersonal costs. Innovative
      internet-delivered interventions have been designed to increase accessibility to
      and cost-effectiveness of treatments. These treatments have mainly targeted mild
      to moderate levels of depression. The increased risk associated with severe
      depression, particularly of suicidal ideation often results in this population
      being excluded from research studies. As a result, the effectiveness of internet
      delivered cognitive behavioral therapy (iCBT) in more severely depressed cohorts
      is less researched. OBJECTIVE: The aim of this study is to examine the effect of
      iCBT on symptoms of severe depression, comorbid symptoms of anxiety, and levels
      of work and social functioning. METHODS: Retrospective consent was provided by
      participants with elevated scores (>28 severe depression symptoms) on the Beck
      Depression Inventory (BDI-II) who accessed an iCBT intervention (Space from
      Depression) with support for up to 8 weeks. Data were collected at baseline,
      posttreatment, and 3-month follow-up on the primary outcome (BDI-II), and
      secondary outcomes (the Generalized Anxiety Disorder-7 and the Work and Social
      Adjustment Scale). RESULTS: A significant change was observed on all measures
      between pre- and postmeasurement and maintained at 3-month follow-up. Clinical
      improvement was observed for participants on the BDI-II from pre- to
      postmeasurement, and suicidal ideation also reduced from pre- to postmeasurement.
      CONCLUSIONS: Users of Space from Depression with symptoms of severe depression
      were found to have decreased symptoms of depression and anxiety and increased
      levels of work and social functioning. The intervention also demonstrated its
      potential to decrease suicidal ideation. Further investigation is required to
      determine why some individuals improve, and others do not. iCBT may have the
      potential to be used as an adjunct treatment for severe depression symptoms, but
      participants may require further treatment if they receive iCBT as a standalone
      intervention. Although promising, further research incorporating control groups
      is needed to support the utility of Space from Depression for use in or as an
      adjunct to treatment for severe depression.

PMID- 30279156
TI  - Palivizumab for all children with Down syndrome?

PMID- 30279155
TI  - Proposing a Transactional Model of eHealth Literacy: Concept Analysis.
AB  - BACKGROUND: Electronic health (eHealth) literacy was conceptualized in 2006 as
      the ability of internet users to locate, evaluate, and act upon web-based health
      information. Now, advances in eHealth technology have cultivated transactional
      opportunities for patients to access, share, and monitor health information.
      However, empirical evidence shows that existing models and measures of eHealth
      literacy have limited theoretical underpinnings that reflect the transactional
      capabilities of eHealth. This paper describes a conceptual model based on the
      Transactional Model of Communication (TMC), in which eHealth literacy is
      described as an intrapersonal skillset hypothesized as being dynamic; reciprocal;
      and shaped by social, relational, and cultural contexts. OBJECTIVE: The objective
      of our study was to systematically examine eHealth literacy definitions, models,
      and measures to propose a refined conceptual and operational definition based on
      the TMC. METHODS: Walker and Avant's concept analysis method was used to guide
      the systematic review of eHealth literacy definitions (n=10), rating scales
      (n=6), models (n=4), and peer-reviewed model applications (n=16). Subsequent
      cluster analyses showed salient themes across definitions. Dimensions,
      antecedents, and consequences reflected in models and measures were extracted and
      deductively analyzed based on codes consistent with the TMC. RESULTS: Systematic
      review evidence revealed incongruity between operational eHealth literacy
      included in definitions compared with literacies included within models and
      measures. Theoretical underpinnings of eHealth literacy also remain dismal.
      Despite the transactional capabilities of eHealth, the role of "communication" in
      eHealth literacy remains underdeveloped and does not account for physical and
      cognitive processing abilities necessary for multiway transactions. CONCLUSIONS:
      The Transactional Model of eHealth Literacy and a corresponding definition are
      proposed. In this novel model, eHealth literacy comprises a hierarchical
      intrapersonal skillset that mediates the reciprocal effect of contextual factors
      (ie, user oriented and task oriented) on patient engagement in health care. More
      specifically, the intrapersonal skillset counteracts the negative effect of
      "noise" (or impediments) produced by social and relational contexts. Cutting
      across health and technology literacies, the intrapersonal skillset of eHealth
      literacy is operationalized through four literacies that correspond with discrete
      operative skills: (1) functional (ie, locate and understand); (2) communicative
      (ie, exchange); (3) critical (ie, evaluate); and (4) translational (ie, apply).

PMID- 30279158
TI  - Causes and characteristics of injury in paediatric major trauma and trends over
      time.
AB  - OBJECTIVE: To investigate causes, characteristics and temporal trends of
      paediatric major trauma. DESIGN: A retrospective review of paediatric major
      trauma (<16 years of age) was conducted using data from the population-based
      Victorian State Trauma Registry from 2006 to 2016. Temporal trends in population
      based incidence rates were evaluated using Poisson regression. SETTING: Victoria,
      Australia. RESULTS: Of the 1511 paediatric major trauma patients, most were male
      (68%), had sustained blunt trauma (87%) and had injuries resulting from
      unintentional events (91%). Motor vehicle collisions (15%), struck by/collisions
      with an object or person (14%) and low falls (13%) were the leading mechanisms of
      injury. Compared with those aged 1-15 years, a greater proportion of non
      accidental injury events were observed in infants (<1 year) (32%). For all
      patients, isolated head injury (29%), other/multitrauma (27%) and head and other
      injuries (24%) were the most prevalent injury groups. The incidence of paediatric
      major trauma did not change over the study period (incidence rate ratio
      (IRR)=0.97; 95% CI 0.92 to 1.02; p=0.27), which was consistent in all age groups.
      There was a 3% per year decline in the incidence of transport events (IRR=0.97;
      95% CI 0.94 to 0.99; p=0.005), but no change in the incidence of falls of any
      type (IRR=1.01; 95% CI 0.97 to 1.04; p=0.70) or other events (IRR=1.00; 95% CI
      0.97 to 1.02; p=0.79). The overall in-hospital mortality rate was 7.2%.
      CONCLUSIONS: This study demonstrated no change in the incidence of paediatric
      major trauma over an 11-year period. Given the potential lifelong impacts of
      serious injury in children, additional investment and coordination of injury
      prevention activities are required.

PMID- 30279160
TI  - David Oliver: The crisis in care home supply.

PMID- 30279159
TI  - Impact of oral anticoagulants on 30-day readmission: a study from a single
      academic centre.
AB  - Researchers are extensively searching for modifiable risk factors including high
      risk medications such as anticoagulation to avoid rehospitalisation. The
      influence of oral anticoagulant therapy on hospital readmission is not known. We
      investigated the impact of warfarin and direct oral anticoagulants (DOACs) on all
      cause 30-day hospital readmission retrospectively in an academic centre. We study
      the eligible cohort of 1781 discharges over 2-year period. Data on age, gender,
      diagnoses, 30-day hospital readmission, discharge medications and variables in
      the HOSPITAL score (Haemoglobin level at discharge, Oncology at discharge, Sodium
      level at discharge, Procedure during hospitalisation, Index admission, number of
      hospital Admissions, Length of stay) and LACE index (Length of stay,
      Acute/emergent admission, Charlson comorbidity index score, Emergency department
      visits in previous 6 months), which have higher predictability for readmission
      were extracted and matched for analysis. Warfarin was the most common
      anticoagulant prescribed at discharge (273 patients) with a readmission rate of
      20% (p<0.01). DOACs were used by 94 patients at discharge with a readmission rate
      of 4% (p=0.219). Multivariate logistic regression showed an increased risk of
      readmission with warfarin therapy (OR 1.36, p=0.045). Logistic regression did not
      show DOACs to be a risk factor for hospital readmission. Our data suggests that
      warfarin therapy is a risk factor for all-cause 30-day hospital readmission. DOAC
      therapy is not found to be associated with a higher risk of hospital readmission.
      Warfarin anticoagulation may be an important target for interventions to reduce
      hospital readmissions.

PMID- 30279161
TI  - Preproglucagon Neurons in the Nucleus of the Solitary Tract are the Main Source
      of Brain GLP-1, Mediate Stress-Induced Hypophagia, and Limit Unusually Large
      Intakes of Food.
AB  - Centrally administered glucagon-like peptide-1 (GLP-1) supresses food intake.
      Here we demonstrate that GLP-1-producing (PPG) neurons in the nucleus tractus
      solitarii (NTS) are the predominant source of endogenous GLP-1 within the brain.
      Selective ablation of NTS PPG neurons by viral expression of diphtheria toxin
      subunit A (DTA) substantially reduced active GLP-1 concentrations in brain and
      spinal cord. Contrary to expectations, this loss of central GLP-1 had no
      significant effect on ad libitum feeding of mice, affecting neither daily chow
      intake nor body weight or glucose tolerance. Only after bigger challenges to
      homeostasis were PPG neurons necessary for food intake control. PPG-ablated mice
      increased food intake following a prolonged fast and after a liquid diet preload.
      Consistent with our ablation data, acute inhibition of hM4Di-expressing PPG
      neurons did not affect ad libitum feeding, however, it increased post-fast
      refeeding intake and blocked stress-induced hypophagia. Additionally,
      chemogenetic PPG neuron activation through hM3Dq caused a strong acute anorectic
      effect. We conclude that PPG neurons are not involved in primary intake
      regulation, but form part of a secondary satiation/satiety circuit, activated by
      both psychogenic stress and large meals. Given their hypophagic capacity, PPG
      neurons might be an attractive drug target in obesity treatment.

PMID- 30279163
TI  - Pygo2 Regulates Adiposity and Glucose Homeostasis via beta-Catenin-Axin2-GSK3beta
      Signaling Pathway.
AB  - Wnt/beta-catenin signaling plays a key role in regulating adipogenesis through
      indirectly inhibiting the expression of C/EBPalpha and peroxisome proliferator
      activated receptor gamma (PPARgamma); however, the detailed molecular mechanism
      remains poorly understood. Moreover, the factor(s) that determines the Wnt/beta
      catenin output level during adipogenesis is also not completely defined. In this
      study, we showed that Pygo2 exhibited a declined expression pattern during
      adipocyte differentiation, resulting in an attenuated Wnt/beta-catenin output
      level. The mechanism study indicated that Pygo2 inhibition led to the
      downregulation of Axin2, a constitutive Wnt target, in the cytoplasm.
      Consequently, Axin2-bound GSK3beta was released and translocated into the nucleus
      to phosphorylate C/EBPbeta and Snail, resulting in an increase in the DNA binding
      activity of C/EBPbeta and decreased protein stability of Snail, which
      subsequently activated the expression of C/EBPalpha and PPARgamma. Consistent
      with this, embryonic fibroblasts from Pygo2-/- mice exhibited spontaneous
      adipocyte differentiation, and adipocyte precursor-specific Pygo2-deficient mice
      exhibited increased adiposity with decreased energy expenditure. We further
      showed impaired glucose tolerance and decreased systemic insulin sensitivity in
      Pygo2-deficient mice. Our study revealed an association between Pygo2 function
      and obesity or diabetes.

PMID- 30279164
TI  - Obesity-Associated miR-199a/214 Cluster Inhibits Adipose Browning via PRDM16-PGC
      1alpha Transcriptional Network.
AB  - miRNAs are important regulators of differentiation, development, and function of
      brown and beige fat cells. In this study, we identify the role of the miR
      199a/214 cluster in the regulation of brown and beige adipocyte development and
      thermogenesis in vitro and in vivo. We show that expression of the miR-199a/214
      cluster is dramatically decreased during brown and beige adipocyte
      differentiation and in response to cold exposure or beta-adrenergic receptor
      activation. The cluster levels are significantly upregulated in the adipose
      tissues of obese mice and human subjects. Overexpression of the miR-199a/214
      cluster suppresses brown adipocyte differentiation and inhibits thermogenic gene
      expression and mitochondrial respiration, whereas knockdown of the cluster
      increases thermogenic gene expression and mitochondrial function in beige
      adipocytes. In addition, inhibition of the miR-199a/214 cluster promotes beiging
      effects in vivo. We further show that miR-199a/214 suppresses brown adipocyte
      differentiation and beige fat development by directly targeting PRDM16 and
      peroxisome PGC-1alpha, two key transcriptional regulators of adipose browning.
      Together, these observations reveal that the miR-199a/214 cluster is a key
      negative regulator of brown and beige fat development and thermogenesis.

PMID- 30279157
TI  - Research priorities for childhood chronic conditions: a workshop report.
AB  - BACKGROUND: Chronic conditions are the leading cause of mortality, morbidity and
      disability in children. However, children and caregivers are rarely involved in
      identifying research priorities, which may limit the value of research in
      supporting patient-centred practice and policy. OBJECTIVE: To identify priorities
      of patients, caregivers and health professionals for research in childhood
      chronic conditions and describe the reason for their choices. SETTING: An
      Australian paediatric hospital and health consumer organisations. METHODS:
      Recruited participants (n=73) included patients aged 8 to 14 years with a chronic
      condition (n=3), parents/caregivers of children aged 0 to 18 years with a chronic
      condition (n=19), representatives from consumer organisations (n=13) and health
      professionals including clinicians, researches (n=38) identified and discussed
      research priorities. Transcripts were thematically analysed. RESULTS: Seventy
      eight research questions were identified. Five themes underpinned participants'
      priorities: maintaining a sense of normality (enabling participation in school,
      supporting social functioning, promoting understanding and acceptance),
      empowering self-management and partnership in care (overcoming communication
      barriers, gaining knowledge and skills, motivation for treatment adherence,
      making informed decisions, access and understanding of complementary and
      alternative therapies),strengthening ability to cope (learning to have a positive
      outlook, preparing for home care management, transitioning to adult services),
      broadening focus to family (supporting sibling well-being, parental resilience
      and financial loss, alleviating caregiver burden), and improving quality and
      scope of health and social care (readdressing variability and inequities,
      preventing disease complications and treatment side effects, identifying risk
      factors, improving long-term outcomes, harnessing technology, integrating
      multidisciplinary services). CONCLUSION: Research priorities identified by
      children, caregivers and health professionals emphasise a focus on life
      participation, psychosocial well-being, impact on family and quality of care.
      These priorities may be used by funding and policy organisations in establishing
      a paediatric research agenda.

PMID- 30279165
TI  - Impact of automated photo enforcement of vehicle speed in school zones:
      interrupted time series analysis.
AB  - OBJECTIVE: Measure the impact of automated photo speed enforcement in school
      zones on motorist speed and speeding violation rates during school travel.
      METHODS: Automated enforcement cameras, active during school commuting hours,
      were installed around four elementary schools in Seattle, Washington, USA in
      2012. We examined the effect of automated enforcement on motorist speeds and
      speed violation rates during the citation period (10 December 2012 to 15 January
      2015) compared with the 'warning' period (1 November to 9 December 2012). We
      evaluated outcomes with an interrupted time series approach using multilevel
      mixed linear regression. RESULTS: Motorist speed violation rates decreased by
      nearly half in the citation period compared with the warning period (standardised
      incident rate ratio 0.53, 95% CI 0.42 to 0.66). The hourly maximum violation
      speed and mean hourly speeds decreased 2.1 MPH (95% CI -2.88 to -1.39) and 1.1
      MPH (95% CI -1.64 to - 0.60), respectively. The impact of automated enforcement
      was sustained during the second year of implementation. CONCLUSION: Automated
      photo enforcement of speed limit in school zones was effective at reducing
      motorist speed violations and also achieved a significant reduction in mean
      motorist speed.

PMID- 30279166
TI  - The receptor tyrosine kinase HIR-1 coordinates HIF-independent responses to
      hypoxia and extracellular matrix injury.
AB  - Inadequate tissue oxygen, or hypoxia, is a central concept in the pathophysiology
      of ischemic disorders and cancer. Hypoxia promotes extracellular matrix (ECM)
      remodeling, cellular metabolic adaptation, and cancer cell metastasis. To
      discover new pathways through which cells respond to hypoxia, we performed a
      large-scale forward genetic screen in Caenorhabditis elegans and identified a
      previously uncharacterized receptor tyrosine kinase named HIR-1. Loss of function
      in hir-1 phenocopied the impaired ECM integrity associated with hypoxia or
      deficiency in the oxygen-dependent dual oxidase, heme peroxidases, or cuticular
      collagens involved in ECM homeostasis. Genetic suppressor screens identified NHR
      49 and MDT-15 as transcriptional regulators downstream of HIR-1. Furthermore, hir
      1 mutants showed defects in adapting to and recovering from prolonged severe
      hypoxia. We propose that C. elegans HIR-1 coordinates hypoxia-inducible factor
      independent responses to hypoxia and hypoxia-associated ECM remodeling through
      mechanisms that are likely conserved in other organisms.

PMID- 30279162
TI  - FOXO1 Deletion Reverses the Effect of Diabetic-Induced Impaired Fracture Healing.
AB  - Type 1 diabetes impairs fracture healing. We tested the hypothesis that diabetes
      affects chondrocytes to impair fracture healing through a mechanism that involves
      the transcription factor FOXO1. Type 1 diabetes was induced by streptozotocin in
      mice with FOXO1 deletion in chondrocytes (Col2alpha1Cre+FOXO1L/L) or littermate
      controls (Col2alpha1Cre-FOXO1L/L) and closed femoral fractures induced. Diabetic
      mice had 77% less cartilage and 30% less bone than normoglycemics evaluated
      histologically and by micro-computed tomography. Both were reversed with lineage
      specific FOXO1 ablation. Diabetic mice had a threefold increase in osteoclasts
      and a two- to threefold increase in RANKL mRNA or RANKL-expressing chondrocytes
      compared with normoglycemics. Both parameters were rescued by FOXO1 ablation in
      chondrocytes. Conditions present in diabetes, high glucose (HG), and increased
      advanced glycation end products (AGEs) stimulated FOXO1 association with the
      RANKL promoter in vitro, and overexpression of FOXO1 increased RANKL promoter
      activity in luciferase reporter assays. HG and AGE stimulated FOXO1 nuclear
      localization, which was reversed by insulin and inhibitors of TLR4, histone
      deacetylase, nitric oxide, and reactive oxygen species. The results indicate that
      chondrocytes play a prominent role in diabetes-impaired fracture healing and that
      high levels of glucose, AGEs, and tumor necrosis factor-alpha, which are elevated
      by diabetes, alter RANKL expression in chondrocytes via FOXO1.

PMID- 30279167
TI  - The LKB1-AMPK-alpha1 signaling pathway triggers hypoxic pulmonary
      vasoconstriction downstream of mitochondria.
AB  - Hypoxic pulmonary vasoconstriction (HPV), which aids ventilation-perfusion
      matching in the lungs, is triggered by mechanisms intrinsic to pulmonary arterial
      smooth muscles. The unique sensitivity of these muscles to hypoxia is conferred
      by mitochondrial cytochrome c oxidase subunit 4 isoform 2, the inhibition of
      which has been proposed to trigger HPV through increased generation of
      mitochondrial reactive oxygen species. Contrary to this model, we have shown that
      the LKB1-AMPK-alpha1 signaling pathway is critical to HPV. Spectral Doppler
      ultrasound revealed that deletion of the AMPK-alpha1 catalytic subunit blocked
      HPV in mice during mild (8% O2) and severe (5% O2) hypoxia, whereas AMPK-alpha2
      deletion attenuated HPV only during severe hypoxia. By contrast, neither of these
      genetic manipulations affected serotonin-induced reductions in pulmonary vascular
      flow. HPV was also attenuated by reduced expression of LKB1, a kinase that
      activates AMPK during energy stress, but not after deletion of CaMKK2, a kinase
      that activates AMPK in response to increases in cytoplasmic Ca2+ Fluorescence
      imaging of acutely isolated pulmonary arterial myocytes revealed that AMPK-alpha1
      or AMPK-alpha2 deletion did not affect mitochondrial membrane potential during
      normoxia or hypoxia. However, deletion of AMPK-alpha1, but not of AMPK-alpha2,
      blocked hypoxia from inhibiting KV1.5, the classical "oxygen-sensing" K+ channel
      in pulmonary arterial myocytes. We conclude that LKB1-AMPK-alpha1 signaling
      pathways downstream of mitochondria are critical for the induction of HPV, in a
      manner also supported by AMPK-alpha2 during severe hypoxia.

PMID- 30279168
TI  - Soluble gp130 prevents interleukin-6 and interleukin-11 cluster signaling but not
      intracellular autocrine responses.
AB  - Interleukin-6 (IL-6) is a proinflammatory cytokine of the IL-6 family, members of
      which signal through a complex of a cytokine-specific receptor and the signal
      transducing subunit gp130. The interaction of IL-6 with the membrane-bound IL-6
      receptor (IL-6R) and gp130 stimulates "classic signaling," whereas the binding of
      IL-6 and a soluble version of the IL-6R to gp130 stimulates "trans-signaling."
      Alternatively, "cluster signaling" occurs when membrane-bound IL-6:IL-6R
      complexes on transmitter cells activate gp130 receptors on neighboring receiver
      cells. The soluble form of gp130 (sgp130) is a selective trans-signaling
      inhibitor, but it does not affect classic signaling. We demonstrated that the
      interaction of soluble gp130 with natural and synthetic membrane-bound IL-6:IL-6R
      complexes inhibited IL-6 cluster signaling. Similarly, IL-11 cluster signaling
      through the IL-11R to gp130 was also inhibited by soluble gp130. However,
      autocrine classic and trans-signaling was not inhibited by extracellular
      inhibitors such as sgp130 or gp130 antibodies. Together, our results suggest that
      autocrine IL-6 signaling may occur intracellularly.

PMID- 30279170
TI  - Sixty seconds on . . . monkeypox.

PMID- 30279169
TI  - The bacterial Ras/Rap1 site-specific endopeptidase RRSP cleaves Ras through an
      atypical mechanism to disrupt Ras-ERK signaling.
AB  - The Ras-extracellular signal-regulated kinase pathway is critical for controlling
      cell proliferation, and its aberrant activation drives the growth of various
      cancers. Because many pathogens produce toxins that inhibit Ras activity, efforts
      to develop effective Ras inhibitors to treat cancer could be informed by studies
      of Ras inhibition by pathogens. Vibrio vulnificus causes fatal infections in a
      manner that depends on multifunctional autoprocessing repeats-in-toxin, a toxin
      that releases bacterial effector domains into host cells. One such domain is the
      Ras/Rap1-specific endopeptidase (RRSP), which site-specifically cleaves the
      Switch I domain of the small GTPases Ras and Rap1. We solved the crystal
      structure of RRSP and found that its backbone shares a structural fold with the
      EreA/ChaN-like superfamily of enzymes. Unlike other proteases in this family,
      RRSP is not a metalloprotease. Through nuclear magnetic resonance analysis and
      nucleotide exchange assays, we determined that the processing of KRAS by RRSP did
      not release any fragments or cause KRAS to dissociate from its bound nucleotide
      but instead only locally affected its structure. However, this structural
      alteration of KRAS was sufficient to disable guanine nucleotide exchange factor
      mediated nucleotide exchange and prevent KRAS from binding to RAF. Thus, RRSP is
      a bacterial effector that represents a previously unrecognized class of protease
      that disconnects Ras from its signaling network while inducing limited structural
      disturbance in its target.

PMID- 30279171
TI  - Two Win Nobel for Immune Regulation Discoveries.
AB  - Two researchers-James Allison, PhD, and Tasuku Honjo, MD, PhD-will share this
      year's Nobel Prize in Physiology or Medicine for their discoveries that CTLA4 and
      PD-1, respectively, serve as checkpoints that limit the ability of T cells to
      attack malignant cells.

PMID- 30279172
TI  - Age-Related Changes in HAPLN1 Increase Lymphatic Permeability and Affect Routes
      of Melanoma Metastasis.
AB  - Older melanoma patients have lower rates of sentinel lymph node (LN) metastases
      yet paradoxically have inferior survival. Patient age correlated with an
      inability to retain Technetium radiotracer during sentinel LN biopsy in over 1000
      patients, and high technecium counts correlated to better survival. We
      hypothesized that loss of integrity in the lymphatic vasculature due to ECM
      degradation might play a role. We have implicated HAPLN1 in age-dependent ECM
      degradation in the dermis. Here we queried whether HAPLN1 could be altered in the
      lymphatic ECM. Lymphatic HAPLN1 expression was prognostic of long-term patient
      survival. Adding rHAPLN1 to aged fibroblast ECMs in vitro reduced endothelial
      permeability via modulation of VE-Cadherin junctions, whereas endothelial
      permeability was increased following HAPLN1-knockdown in young fibroblasts. In
      vivo, reconstitution of HAPLN1 in aged mice increased the number of LN
      metastases, but reduced visceral metastases. These data suggest that age-related
      changes in ECM can contribute to impaired lymphatics.

PMID- 30279173
TI  - Remodeling of the collagen matrix in aging skin promotes melanoma metastasis and
      affects immune cell motility.
AB  - Physical changes in skin are among the most visible signs of aging. We found that
      young dermal fibroblasts secrete high levels of extracellular matrix (ECM)
      constituents, including proteoglycans, glycoproteins and cartilage-linking
      proteins. The most abundantly secreted was HAPLN1, a hyaluronic and proteoglycan
      link protein. HAPLN1 was lost in aged fibroblasts, resulting in a more aligned
      ECM that promoted metastasis of melanoma cells. Reconstituting HAPLN1 inhibited
      metastasis in an aged microenvironment, in 3D skin reconstruction models, and in
      vivo. Intriguingly, aged fibroblast-derived matrices had the opposite effects on
      the migration of T-cells, inhibiting their motility. HAPLN1 treatment of aged
      fibroblasts restored motility of mononuclear immune cells, while impeding that of
      polymorphonuclear immune cells, which in turn affected Treg recruitment. These
      data suggest while age-related physical changes in the ECM can promote tumor cell
      motility, they may adversely impact the motility of some immune cells, resulting
      in an overall change in the immune microenvironment. Understanding the physical
      changes in aging skin may provide avenues for more effective therapy for older
      melanoma patients.

PMID- 30279174
TI  - Performance analysis of SiRe next-generation sequencing panel in diagnostic
      setting: focus on NSCLC routine samples.
AB  - AIMS: Following the development for liquid biopsies of the SiRe next-generation
      sequencing (NGS) panel that covers 568 clinical relevant mutations in EGFR, KRAS,
      NRAS, BRAF, cKIT and PDGFRa genes, in this current study, we apply this small NGS
      panel on tissue samples of lung cancer. METHODS: A total of 322 specimens were
      prospectively tested. Technical parameters were analysed on both cytological and
      histological samples. In a subset of 75 samples, the EGFR SiRe results were
      compared with those generated by the European Community (CE)-IVD EGFR assay on
      Idylla platform. Clinical outcomes of 11 patients treated, on the basis of SiRe
      results, were also evaluated. RESULTS: Only 28 (8.7%) specimens failed to produce
      a library; out of the 294 remaining samples, a total of 168 somatic mutations
      were found. In nearly all instances (74/75-99%), the EGFR SiRe results were
      confirmed by Idylla. In general, SiRe analytical parameters were excellent.
      However, histological and cytological specimens differed in relation to average
      reads for sample, mean number of mapped reads, median read length and average
      reads for amplicon. Treatment outcome evaluation in 11 patients showed a partial
      response in 82 % (9/11) patients with a median progression-free survival of 340
      days. CONCLUSIONS: The small gene panel SiRe is a clinically relevant tool useful
      to widespread the adoption of NGS in predictive molecular pathology laboratories.

PMID- 30279175
TI  - Making sense of sparse data with neural encoding strategies.

PMID- 30279176
TI  - Notch2-dependent DC2s mediate splenic germinal center responses.
AB  - CD4+ T follicular helper (TFH) cells support germinal center (GC) reactions
      promoting humoral immunity. Dendritic cell (DC) diversification into genetically
      distinct subsets allows for specialization in promoting responses against several
      types of pathogens. Whether any classical DC (cDC) subset is required for humoral
      immunity is unknown, however. We tested several genetic models that selectively
      ablate distinct DC subsets in mice for their impact on splenic GC reactions. We
      identified a requirement for Notch2-dependent cDC2s, but not Batf3-dependent
      cDC1s or Klf4-dependent cDC2s, in promoting TFH and GC B cell formation in
      response to sheep red blood cells and inactivated Listeria monocytogenes This
      effect was mediated independent of Il2ra and several Notch2-dependent genes
      expressed in cDC2s, including Stat4 and Havcr2 Notch2 signaling during cDC2
      development also substantially reduced the efficiency of cDC2s for presentation
      of MHC class II-restricted antigens, limiting the strength of CD4 T cell
      activation. Together, these results demonstrate a nonredundant role for the
      Notch2-dependent cDC2 subset in supporting humoral immune responses.

PMID- 30279177
TI  - Amphiregulin-producing gammadelta T cells are vital for safeguarding oral barrier
      immune homeostasis.
AB  - gammadelta T cells are enriched at barrier sites such as the gut, skin, and lung,
      where their roles in maintaining barrier integrity are well established. However,
      how these cells contribute to homeostasis at the gingiva, a key oral barrier and
      site of the common chronic inflammatory disease periodontitis, has not been
      explored. Here we demonstrate that the gingiva is policed by gammadelta T cells
      with a T cell receptor (TCR) repertoire that diversifies during development.
      Gingival gammadelta T cells accumulated rapidly after birth in response to
      barrier damage, and strikingly, their absence resulted in enhanced pathology in
      murine models of the oral inflammatory disease periodontitis. Alterations in
      bacterial communities could not account for the increased disease severity seen
      in gammadelta T cell-deficient mice. Instead, gingival gammadelta T cells
      produced the wound healing associated cytokine amphiregulin, administration of
      which rescued the elevated oral pathology of tcrdelta -/- mice. Collectively, our
      results identify gammadelta T cells as critical constituents of the immuno
      surveillance network that safeguard gingival tissue homeostasis.

PMID- 30279179
TI  - Education can reduce health differences related to genetic risk of obesity.
AB  - This work investigates whether genetic makeup moderates the effects of education
      on health. Low statistical power and endogenous measures of environment have been
      obstacles to the credible estimation of such gene-by-environment interactions. We
      overcome these obstacles by combining a natural experiment that generated
      variation in secondary education with polygenic scores for a quarter-million
      individuals. The additional schooling affected body size, lung function, and
      blood pressure in middle age. The improvements in body size and lung function
      were larger for individuals with high genetic predisposition to obesity. As a
      result, education reduced the gap in unhealthy body size between those in the top
      and bottom terciles of genetic risk of obesity from 20 to 6 percentage points.

PMID- 30279178
TI  - Enhanced dynamic nuclear polarization via swept microwave frequency combs.
AB  - Dynamic nuclear polarization (DNP) has enabled enormous gains in magnetic
      resonance signals and led to vastly accelerated NMR/MRI imaging and spectroscopy.
      Unlike conventional cw-techniques, DNP methods that exploit the full electron
      spectrum are appealing since they allow direct participation of all electrons in
      the hyperpolarization process. Such methods typically entail sweeps of microwave
      radiation over the broad electron linewidth to excite DNP but are often
      inefficient because the sweeps, constrained by adiabaticity requirements, are
      slow. In this paper, we develop a technique to overcome the DNP bottlenecks set
      by the slow sweeps, using a swept microwave frequency comb that increases the
      effective number of polarization transfer events while respecting adiabaticity
      constraints. This allows a multiplicative gain in DNP enhancement, scaling with
      the number of comb frequencies and limited only by the hyperfine-mediated
      electron linewidth. We demonstrate the technique for the optical
      hyperpolarization of 13C nuclei in powdered microdiamonds at low fields,
      increasing the DNP enhancement from 30 to 100 measured with respect to the
      thermal signal at 7T. For low concentrations of broad linewidth electron radicals
      [e.g., TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl)], these multiplicative
      gains could exceed an order of magnitude.

PMID- 30279180
TI  - Structural characterization of the D290V mutation site in hnRNPA2 low-complexity
      domain polymers.
AB  - Human genetic studies have given evidence of familial, disease-causing mutations
      in the analogous amino acid residue shared by three related RNA binding proteins
      causative of three neurological diseases. Alteration of aspartic acid residue 290
      of hnRNPA2 to valine is believed to predispose patients to multisystem
      proteinopathy. Mutation of aspartic acid 262 of hnRNPA1 to either valine or
      asparagine has been linked to either amyotrophic lateral sclerosis or multisystem
      proteinopathy. Mutation of aspartic acid 378 of hnRNPDL to either asparagine or
      histidine has been associated with limb girdle muscular dystrophy. All three of
      these aspartic acid residues map to evolutionarily conserved regions of low
      complexity (LC) sequence that may function in states of either intrinsic disorder
      or labile self-association. Here, we present a combination of solid-state NMR
      spectroscopy with segmental isotope labeling and electron microscopy on the LC
      domain of the hnRNPA2 protein. We show that, for both the wild-type protein and
      the aspartic acid 290-to-valine mutant, labile polymers are formed in which the
      LC domain associates into an in-register cross-beta conformation. Aspartic acid
      290 is shown to be charged at physiological pH and immobilized within the polymer
      core. Polymers of the aspartic acid 290-to-valine mutant are thermodynamically
      more stable than wild-type polymers. These observations give evidence that
      removal of destabilizing electrostatic interactions may be responsible for the
      increased propensity of the mutated LC domains to self-associate in disease
      causing conformations.

PMID- 30279183
TI  - Using a natural experiment to estimate the electoral consequences of terrorist
      attacks.
AB  - This study investigates the consequences of terrorist attacks for political
      behavior by leveraging a natural experiment in Spain. We study eight attacks
      against civilians, members of the military, and police officers perpetrated
      between 1989 and 1997 by Euskadi Ta Askatasuna (ETA), a Basque terrorist
      organization that was active between 1958 and 2011. We use nationally and
      regionally representative surveys that were being fielded when the attacks
      occurred to estimate the causal effect of terrorist violence on individuals'
      intent to participate in democratic elections as well as on professed support for
      the incumbent party. We find that both lethal and nonlethal terrorist attacks
      significantly increase individuals' intent to participate in a future democratic
      election. The magnitude of this impact is larger when attacks are directed
      against civilians than when directed against members of the military or the
      police. We find no evidence that the attacks change support for the incumbent
      party. These results suggest that terrorist attacks enhance political engagement
      of citizens.

PMID- 30279181
TI  - Long noncoding RNA SYISL regulates myogenesis by interacting with polycomb
      repressive complex 2.
AB  - Although many long noncoding RNAs (lncRNAs) have been identified in muscle, their
      physiological function and regulatory mechanisms remain largely unexplored. In
      this study, we systematically characterized the expression profiles of lncRNAs
      during C2C12 myoblast differentiation and identified an intronic lncRNA, SYISL
      (SYNPO2 intron sense-overlapping lncRNA), that is highly expressed in muscle.
      Functionally, SYISL promotes myoblast proliferation and fusion but inhibits
      myogenic differentiation. SYISL knockout in mice results in significantly
      increased muscle fiber density and muscle mass. Mechanistically, SYISL recruits
      the enhancer of zeste homolog 2 (EZH2) protein, the core component of polycomb
      repressive complex 2 (PRC2), to the promoters of the cell-cycle inhibitor gene
      p21 and muscle-specific genes such as myogenin (MyoG), muscle creatine kinase
      (MCK), and myosin heavy chain 4 (Myh4), leading to H3K27 trimethylation and
      epigenetic silencing of target genes. Taken together, our results reveal that
      SYISL is a repressor of muscle development and plays a vital role in PRC2
      mediated myogenesis.

PMID- 30279182
TI  - Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of
      nucleation and activation of caspase-1.
AB  - Canonical inflammasomes are cytosolic supramolecular complexes that activate
      caspase-1 upon sensing extrinsic microbial invasions and intrinsic sterile stress
      signals. During inflammasome assembly, adaptor proteins ASC and NLRC4 recruit
      caspase-1 through homotypic caspase recruitment domain (CARD) interactions,
      leading to caspase-1 dimerization and activation. Activated caspase-1 processes
      proinflammatory cytokines and Gasdermin D to induce cytokine maturation and
      pyroptotic cell death. Here, we present cryo-electron microscopy (cryo-EM)
      structures of NLRC4 CARD and ASC CARD filaments mediated by conserved three types
      of asymmetric interactions (types I, II, and III). We find that the CARDs of
      these two adaptor proteins share a similar assembly pattern, which matches that
      of the caspase-1 CARD filament whose structure we defined previously. These data
      indicate a unified mechanism for downstream caspase-1 recruitment through CARD
      CARD interactions by both adaptors. Using structure modeling, we further show
      that full-length NLRC4 assembles via two separate symmetries at its CARD and its
      nucleotide-binding domain (NBD), respectively.

PMID- 30279184
TI  - Model of bacterial toxin-dependent pathogenesis explains infective dose.
AB  - The initial amount of pathogens required to start an infection within a
      susceptible host is called the infective dose and is known to vary to a large
      extent between different pathogen species. We investigate the hypothesis that the
      differences in infective doses are explained by the mode of action in the
      underlying mechanism of pathogenesis: Pathogens with locally acting mechanisms
      tend to have smaller infective doses than pathogens with distantly acting
      mechanisms. While empirical evidence tends to support the hypothesis, a formal
      theoretical explanation has been lacking. We give simple analytical models to
      gain insight into this phenomenon and also investigate a stochastic, spatially
      explicit, mechanistic within-host model for toxin-dependent bacterial infections.
      The model shows that pathogens secreting locally acting toxins have smaller
      infective doses than pathogens secreting diffusive toxins, as hypothesized. While
      local pathogenetic mechanisms require smaller infective doses, pathogens with
      distantly acting toxins tend to spread faster and may cause more damage to the
      host. The proposed model can serve as a basis for the spatially explicit analysis
      of various virulence factors also in the context of other problems in infection
      dynamics.

PMID- 30279185
TI  - Development and validation of an automated algorithm for identifying patients at
      high risk for drug-induced hypoglycemia.
AB  - PURPOSE: Hypoglycemia is one of the most concerning adverse drug events in
      hospitalized patients. Using information from institutional electronic health
      records, we aimed to develop dynamic predictive models to identify patients at
      high risk for hypoglycemia during antihyperglycemic therapy. METHODS: The study
      population consisted of 21,840 patients who received antihyperglycemic medication
      on any of the first 5 hospital days (the "risk model days") at 2 large hospitals.
      Data on candidate predictors were extracted from discrete electronic health
      record fields to construct models for predicting hypoglycemia within 24 hours
      after each risk model day. Final models were internally validated by replication
      in 100 bootstrap samples and reapplying model parameters to the original risk
      population. RESULTS: The development and validation sample included 60,762 risk
      model days followed by 1,256 days with hypoglycemic events (2.07 events per 100
      risk model days). The days 3, 4, and 5 models presented similar associations
      between predictors and the risk of hypoglycemia and were therefore collapsed into
      a single model. The strongest hypoglycemia risk factors across all 3 risk periods
      (day 1, day 2, and days 3-5) were blood glucose (BG) fluctuations, BG trend,
      history of hypoglycemia, lower body weight, lower creatinine clearance, use of
      long-acting or high-dose insulin, and sulfonylurea use. C statistics for the 3
      models ranged from 0.844 to 0.887. Depending on the model used, risk scores in
      the upper 90th percentile predicted 48.5-63.1% of actual hypoglycemic events. It
      was estimated that by targeting only patients in the upper 90th percentile,
      providers would need to intervene during fewer than 9 admissions to prevent 1
      hypoglycemic event. CONCLUSION: The developed prediction models were found to
      have excellent discriminative validity and good calibration, allowing clinicians
      to focus interventions on a select high-risk population in which the majority of
      hypoglycemic events occur.

PMID- 30279187
TI  - A Sampling of Highlights from the Literature: Article Recommendations from our
      Deputy and Senior Editors.

PMID- 30279186
TI  - Early childcare type predicts children's emotional and behavioural trajectories
      into middle childhood. Data from the EDEN mother-child cohort study.
AB  - BACKGROUND: The scientific literature on the impact of early childcare on
      children's behavioural and emotional difficulties shows contrasting results. We
      studied this association in France, where childcare is of high quality and
      children enter preschool at the age of 3. METHODS: 1428 children from the EDEN
      (Etude des Determinants du developpement et de la sante de l'ENfant) mother-child
      cohort set up in France (Nancy and Poitiers) were followed up since pregnancy to
      the age of 8 years. Group-based trajectory modelling was used to model their
      trajectories of behavioural and emotional symptoms (emotional symptoms, peer
      relationship problems, hyperactivity/inattention, conduct problems, prosocial
      behaviours) ascertained by three measures (3, 5.5 and 8 years) of the Strengths
      and Difficulties Questionnaire. Using propensity scores and inverse probability
      weights (IPWs) to account for selection and confounding factors, we compared
      children in a childminder's care or in centre-based childcare (from birth to age
      3) with those in informal childcare. RESULTS: Compared with children in informal
      childcare, those who attended centre-based childcare had a lower likelihood of
      having high levels of emotional symptoms (ORIPW-adjusted=0.35, 95% CI 0.17 to
      0.71), peer relationship problems (ORIPW-adjusted=0.31, 95% CI 0.15 to 0.67) and
      low prosocial behaviours (ORIPW-adjusted=0.50, 95% CI 0.28 to 0.90). Those who
      were looked after by a childminder had a higher likelihood of following a high
      trajectory of conduct problems (ORIPW-adjusted=1.72, 95% CI 1.05 to 2.81).
      Attendance of centre-based childcare for more than 1 year was especially
      protective of high levels of emotional, peer-related difficulties and low
      prosocial behaviours. Girls and children from a favourable socioeconomic
      background reaped more benefits of childcare than boys and those from a less
      favourable background. CONCLUSION: High-quality centre-based childcare may be
      linked to lower levels of emotional symptoms.

PMID- 30279188
TI  - Predictive Biomarkers for Checkpoint Immunotherapy: Current Status and Challenges
      for Clinical Application.
AB  - Immune-checkpoint blockade (ICB), in particular PD-1 inhibition, has rapidly
      changed the treatment landscape and altered therapeutic paradigms across many
      tumor types, with unprecedented rates of durable clinical responses in a number
      of cancers. Despite this success, only a subset of patients responds to ICB and,
      as a result, predictive biomarkers would be useful to guide the selection of
      patients for these therapies. This article highlights currently used biomarkers,
      as well as several promising novel candidates, and also discusses the challenges
      involved in establishing their analytic validity and clinical utility. Progress
      is being evaluated in melanoma and non-small cell lung cancer, for which PD-1 +/-
      CTLA-4 inhibitors have become standard therapy, to other malignancies for which
      PD-L1 inhibitors remain investigational. Although single biomarkers have
      substantial limitations, a combination of biomarkers that reflect the interaction
      of host and tumor will likely be needed to provide a reproducible surrogate for
      the benefit of checkpoint modulation. Cancer Immunol Res; 6(10); 1122-8. (c)2018
      AACR.

PMID- 30279189
TI  - PIE-1 Translation in the Germline Lineage Contributes to PIE-1 Asymmetry in the
      Early Caenorhabditis elegans Embryo.
AB  - In the C. elegans embryo, the germline lineage is established through successive
      asymmetric cell divisions that each generate a somatic and a germline daughter
      cell. PIE-1 is an essential maternal factor that is enriched in embryonic
      germline cells and is required for germline specification. We estimated the
      absolute concentration of PIE-1::GFP in germline cells and find that PIE-1::GFP
      concentration increases by roughly 4.5 fold, from 92 nM to 424 nM, between the 1
      and 4-cell stages. Previous studies have shown that the preferential inheritance
      of PIE-1 by germline daughter cells and the degradation of PIE-1 in somatic cells
      are important for PIE-1 enrichment in germline cells. In this study, we provide
      evidence that the preferential translation of maternal PIE-1::GFP transcripts in
      the germline also contributes to PIE-1::GFP enrichment. Through an RNAi screen,
      we identified Y14 and MAG-1 (Drosophila tsunagi and mago nashi) as regulators of
      embryonic PIE-1::GFP levels. We show that Y14 and MAG-1 do not regulate PIE-1
      degradation, segregation or synthesis in the early embryo, but do regulate the
      concentration of maternally-deposited PIE-1::GFP. Taken together, or findings
      point to an important role for translational control in the regulation of PIE-1
      levels in the germline lineage.

PMID- 30279193
TI  - Shipping Out MEK Inhibitor Resistance with SHP2 Inhibitors.
AB  - RAS is one of the most frequently altered oncogenes, yet RAS-driven tumors are
      largely refractory to anticancer therapies. Fedele and colleagues demonstrate
      that SHP2 inhibitors prevent adaptive MEK inhibitor resistance; therefore,
      combining MEK and SHP2 inhibitors represents an exciting new therapeutic approach
      for the treatment of RAS-driven cancers. Cancer Discov; 8(10); 1210-2. (c)2018
      AACR. See related article by Fedele et al., p. 1237.

PMID- 30279194
TI  - Blood-Based Prediction of Tumor Relapse: The cfDNA Forecast.
AB  - Khan and colleagues demonstrate how serial blood-based liquid biopsies
      integrated with imaging and mathematical modeling can accurately "forecast" the
      time to treatment failure in patients with metastatic colorectal cancer treated
      with EGFR blockade, by early detection of molecular alterations associated with
      drug resistance in cell-free DNA. Cancer Discov; 8(10); 1213-5. (c)2018 AACR See
      related article by Khan et al., p. 1270.

PMID- 30279195
TI  - Different Originating Cells Underlie Intertumoral Heterogeneity in Lung
      Neuroendocrine Tumors.
AB  - Studies in genetically engineered mouse models of neuroendocrine lung cancer
      suggest that differences in cells of origin underlie subtype variations in this
      class of cancers. These findings highlight the concept that the same driver
      mutations introduced into different cells of origin lead to tumors with the same
      histology but dramatically different metastatic programs and potentially
      different therapeutic responses. Cancer Discov; 8(10); 1216-8. (c)2018 AACR See
      related article by Yang et al., p. 1316.

PMID- 30279196
TI  - Aberrant cerebellar Purkinje cell activity as the cause of motor attacks in a
      mouse model of episodic ataxia type 2.
AB  - Many cerebellar-induced neurological disorders, such as ataxias and cerebellar
      induced dystonias, are associated with abnormal Purkinje cell activity. In
      tottering mice, a well-established mouse model of episodic ataxia type 2 (EA2),
      cerebellar Purkinje cells are required for the initiation of motor attacks. How
      Purkinje cells contribute to the initiation of attacks is not known, and to date
      there are no reports on the activity of Purkinje cells during motor attacks in
      the tottering mice. Here, we show that tottering Purkinje cells exhibit high
      frequency burst firing during attacks, reminiscent of other mouse models of
      cerebellar-induced motor dysfunction. We recorded the activity of Purkinje cells
      in awake head-restrained tottering mice at baseline, or during caffeine-induced
      attacks. During motor attacks, firing of Purkinje cells transformed to high
      frequency burst firing. Interestingly, the extent to which the activity of
      Purkinje cells was erratic was correlated with the severity of the motor
      dysfunction. In support of a causal role for erratic activity in generating motor
      dysfunction, we found that direct infusion of the small conductance calcium
      activated potassium (SK) channel activator NS309 into the cerebellum of tottering
      mice in the midst of an attack normalized the firing of Purkinje cells and
      aborted attacks. Conversely, we found that inducing high-frequency burst firing
      of Purkinje cells in wild-type animals is sufficient to produce severe motor
      signs. We report that erratic activity of wild-type Purkinje cells results in
      ataxia and dystonic postures. Moreover, this aberrant activity is the cause of
      motor attacks in the tottering mice.

PMID- 30279198
TI  - Local and systemic metabolic responses during light-induced rapid systemic
      signaling.
AB  - Plants evolved multiple signaling pathways that transduce light-related signals
      between leaves. These are thought to improve light stress acclimation in a
      process termed systemic acquired acclimation (SAA). Although responses to light
      stress have been extensively studied in local leaves, and to a lesser degree in
      systemic leaves, little is known about the responses that occur in the different
      tissues that connect the local to the systemic leaves. These could be important
      in defining the specificity of the systemic response, as well as in supporting
      the generation of different systemic signals. Here we report that local
      application of light stress to one rosette leaf of bolting Arabidopsis thaliana
      plants resulted in a metabolic response that encompassed local, systemic and
      transport tissues (stem tissues that connect the local to the systemic tissues),
      demonstrating a high degree of physical and metabolic continuity between
      different tissues throughout the plant. Our results further indicate that the
      response of many of the systemically altered metabolites is associated with the
      function of the reactive oxygen species wave, and that the level of eight
      different metabolites is altered in a similar manner in all tissues tested
      (local, systemic, and transport). These compounds could define a core metabolic
      signature for light stress that propagates from the local to the systemic leaves.
      Our findings suggest that metabolic changes occurring in cells that connect the
      local and systemic tissues play an important role in SAA and could convey
      specificity to the rapid systemic response of plants to light stress.

PMID- 30279199
TI  - Adherence to AAP Healthy Newborn Discharge Criteria in a Tertiary Care Children's
      Hospital.
AB  - OBJECTIVES: In 2015, the American Academy of Pediatrics (AAP) published an
      updated consensus statement containing 17 discharge recommendations for healthy
      term newborn infants. In this study, we identify whether the AAP criteria were
      met before discharge at a tertiary care academic children's hospital. METHODS: A
      stratified random sample of charts from newborns who were discharged between June
      1, 2015, and May 31, 2016, was reviewed. Of the 531 charts reviewed, 433 were
      included in the study. A review of each chart was performed, and data were
      collected. RESULTS: Descriptive statistics for our study population (N = 433)
      revealed that all 17 criteria were followed <5% of the time. The following
      criteria were met 100% of the time: clinical course and physical examination,
      postcircumcision bleeding, availability of family members or health care
      providers to address follow-up concerns, anticipatory guidance, first appointment
      with the physician scheduled or parents knowing how to do so, pulse oximetry
      screening, and hearing screening. These criteria were met at least 95% to 99% of
      the time: appropriate vital signs, regular void and stool frequency, appropriate
      jaundice and sepsis management, and metabolic screening. The following criteria
      were met 50% to 95% of the time: maternal serologies, hepatitis B vaccination,
      and social risk factor assessment. Four of the criteria were met <50% of the
      time: feeding assessment, maternal vaccination, follow-up timing for newborns
      discharged at <48 hours of life, and car safety-seat assessment. CONCLUSIONS: Our
      data reveal that the AAP healthy term newborn discharge recommendations are not
      consistently followed in our institution.

PMID- 30279197
TI  - Six months versus 12 months dual antiplatelet therapy after drug-eluting stent
      implantation in ST-elevation myocardial infarction (DAPT-STEMI): randomised,
      multicentre, non-inferiority trial.
AB  - OBJECTIVE: To show that limiting dual antiplatelet therapy (DAPT) to six months
      in patients with event-free ST-elevation myocardial infarction (STEMI) results in
      a non-inferior clinical outcome versus DAPT for 12 months. DESIGN: Prospective,
      randomised, multicentre, non-inferiority trial. SETTING: Patients with STEMI
      treated with primary percutaneous coronary intervention (PCI) and second
      generation zotarolimus-eluting stent. PARTICIPANTS: Patients with STEMI aged 18
      to 85 that underwent a primary PCI with the implantation of second generation
      drug-eluting stents were enrolled in the trial. Patients that were event-free at
      six months after primary PCI were randomised at this time point. INTERVENTIONS:
      Patients that were taking DAPT and were event-free at six months were randomised
      1:1 to single antiplatelet therapy (SAPT) (ie, aspirin only) or to DAPT for an
      additional six months. All patients that were randomised were then followed for
      another 18 months (ie, 24 months after the primary PCI). MAIN OUTCOME MEASURES:
      The primary endpoint was a composite of all cause mortality, any myocardial
      infarction, any revascularisation, stroke, and thrombolysis in myocardial
      infarction major bleeding at 18 months after randomisation. RESULTS: A total of
      1100 patients were enrolled in the trial between 19 December 2011 and 30 June
      2015. 870 were randomised: 432 to SAPT versus 438 to DAPT. The primary endpoint
      occurred in 4.8% of patients receiving SAPT versus 6.6% of patients receiving
      DAPT (hazard ratio 0.73, 95% confidence interval 0.41 to 1.27, P=0.26). Non
      inferiority was met (P=0.004 for non-inferiority), as the upper 95% confidence
      interval of 1.27 was smaller than the prespecified non-inferiority margin of
      1.66. CONCLUSIONS: DAPT to six months was non-inferior to DAPT for 12 months in
      patients with event-free STEMI at six months after primary PCI with second
      generation drug-eluting stents. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT01459627.

PMID- 30279201
TI  - Realistic (and Still Idealistic) about Cancer Prevention.

PMID- 30279202
TI  - Long non-coding RNA linc-ITGB1 promotes cell proliferation, migration, and
      invasion in human hepatoma carcinoma by up-regulating ROCK1.
AB  - Background: Linc-ITGB1 is a newly identified long non-coding RNA (lncRNA)
      involved in the regulation of cell migration and invasion of gallbladder cancer
      cell lines, while its involvement in human hepatoma carcinoma (HCC) is unknown.
      Methods: In the present study, HCC patient tumor tissues, adjacent healthy
      tissues and whole blood were collected from both HCC patients and healthy
      controls. Expression of LINC-ITGB1 was examined by qRT-PCR. Diagnostic value of
      serum LINC-ITGB1 for HCC was evaluated by receiver operating characteristic (ROC)
      curve analysis. Correlation between the serum LINC-ITGB1 and basic clinical
      information of patients was analyzed by chi-square test. LINC-ITGB1
      overexpression HCC cell lines were established and the effects on cell
      proliferation, migration, and invasion were explored by CCK-8 assay and Transwell
      assay. Effects of LINC-ITGB1 overexpression on Rho-associated, coiled-coil
      containing protein kinase 1 (ROCK1) expression were investigated by Western blot.
      Results: We found that LINC-ITGB1 was up-regulated in tumor tissues than in
      adjacent healthy tissues. Serum levels of LINC-ITGB1 were higher in HCC patients
      than in healthy controls. Serum levels of LINC-ITGB1 were significantly
      correlated with tumor size and distant tumor metastasis. LINC-ITGB1
      overexpression promoted the proliferation, migration, and invasion of HCC cells
      and the expression of ROCK1. ROCK1 inhibitor reduced the effects of LINC-ITGB1
      overexpression on cell proliferation, migration, and invasion. Conclusion: We
      conclude that lncRNA LINC-ITGB1 can promote the proliferation, migration, and
      invasion of HCC cells by up-regulating ROCK1.

PMID- 30279203
TI  - The role of perineural invasion in penile cancer: a meta-analysis and systematic
      review.
AB  - The significance of perineural invasion (PNI) present in penile cancer (PC) is
      controversial. In order to clarify the predictive role of PNI in the inguinal
      lymph node (ILN) metastases (ILNM) and oncologic outcome of patients, we
      performed this meta-analysis and systematic review. The search of PubMed, Embase,
      and Web of Science was conducted for appropriate studies, up to 20 January 2018.
      The pooled odds ratio (OR) and hazard ratio (HR) with their 95% confidence
      interval (CI) were applied to evaluate the difference in ILNM and oncologic
      outcome between patients present with PNI and those who were absent. A total of
      298 in 1001 patients present with PNI were identified in current meta-analysis
      and systematic review. Significant difference was observed in ILNM between PNI
      present and absent from patients with PC (OR = 2.98, 95% CI = 2.00-4.45).
      Patients present with PNI had a worse cancer-specific survival (CSS) (HR = 3.58,
      95% CI = 1.70-7.55) and a higher cancer-specific mortality (CSM) (HR = 2.20, 95%
      CI = 1.06-3.82) than those cases without PNI. This meta-analysis and systematic
      review demonstrated the predictive role of PNI in ILNM, CSS, and CSM for PC
      patients.

PMID- 30279204
TI  - Dihydro-sphingosine 1-phosphate interacts with carrier proteins in a manner
      distinct from that of sphingosine 1-phosphate.
AB  - Dihydro-sphingosine 1-phosphate (DH-S1P) is an analog of sphingosine 1-phosphate
      (S1P), which is a potent lysophospholipid mediator. DH-S1P has been proposed to
      exert physiological properties similar to S1P. Although S1P is known to be
      carried on HDL via apolipoprotein M (apoM), the association between DH-S1P and
      HDL/apoM has not been fully elucidated. Therefore, in the present study, we aimed
      to elucidate this association and to compare it with that of S1P and HDL/apoM.
      First, we investigated the distributions of S1P and DH-S1P among lipoproteins and
      lipoprotein-depleted fractions in human serum and plasma samples and observed
      that both S1P and DH-S1P were detected on HDL; furthermore, elevated amounts of
      DH-S1P in serum samples were distributed to the lipoprotein-depleted fraction to
      a greater degree than to the HDL fraction. Concordantly, a preference for HDL
      over albumin was only observed for S1P, and not for DH-S1P, when the molecules
      were secreted from platelets. Regarding the association with HDL, although both
      S1P and DH-S1P prefer to bind to HDL, HDL preferentially accepts S1P over DH-S1P.
      For the association with apoM, S1P was not detected on HDL obtained from apoM
      knockout mice, while DH-S1P was detected. Moreover, apoM retarded the degradation
      of S1P, but not of DH-S1P. These results suggest that S1P binds to HDL via apoM,
      while DH-S1P binds to HDL in a non-specific manner. Thus, DH-S1P is not a mere
      analog of S1P and might possess unique clinical significance.

PMID- 30279205
TI  - Association between the polymorphisms of CALM1 gene and osteoarthritis risk: a
      meta-analysis based on observational studies.
AB  - The existing studies on the association between polymorphisms of Calmodulin 1
      (CALM1) gene and the risk of osteoarthritis (OA, a complex multifactorial disease
      and a major degenerative form of arthritis) in different populations have yielded
      conflicting findings. Therefore, we conducted a meta-analysis by systematically
      searching PubMed, Embase, Medline, Cochrane Library and Google Scholar, and
      assessing this association by calculating pooled odds ratios with 95% confidence
      intervals. Subgroup analyses stratified by ethnicity, OA type, and genotype were
      also conducted. Six studies (2752 cases and 3259 controls) involving six single
      nucleotide polymorphisms were included. Our data suggested that the T allele and
      genotype TT of the rs12885713 polymorphism, and the C allele of the rs2300496
      polymorphism in the CALM1 gene all increased the risk of OA. The pooled results
      revealed no significant association between the CALM1 rs3213718 polymorphism and
      the risk of OA. Stratification analyses by ethnicity and OA type showed that the
      rs12885713 polymorphism increased the risk of OA among Asians and in knee OA,
      respectively. In conclusion, the rs12885713 and rs2300496 polymorphisms of the
      CALM1 gene may both increase the risk of OA. Owing to the limitations of the
      present study, this finding should be further confirmed in future well-designed
      studies.

PMID- 30279206
TI  - ANRIL promotes chemoresistance via disturbing expression of ABCC1 by regulating
      the expression of Let-7a in colorectal cancer.
AB  - Increasing evidence indicates that long non-coding RNAs (lncRNAs) antisense non
      coding RNA in the INK4 locus (ANRIL) has been involved in various diseases and
      promotes tumorigenesis and cancer progression as an oncogenic gene. However, the
      effect of ANRIL on chemoresistance remains still unknown in colorectal cancer
      (CRC). Here, we investigated ANRIL expression in 63 cases of colorectal cancer
      specimens and matched normal tissues. Results revealed that ANRIL was up
      regulated in tumor tissues samples from patients with CRC and CRC cell lines.
      Increased ANRIL expression in CRC was associated with poor clinical prognosis.
      Kaplan-Meier analysis showed that ANRIL was associated with overall survival of
      patients with colorectal cancer, and patients with high ANRIL expression tended
      to have unfavorable outcome. In vitro experiments revealed that ANRIL knockdown
      significantly inhibited CRC cell proliferation, improved the sensitivity of
      chemotherapy and promoted apoptosis. Further functional assays indicated that
      ANRIL overexpression significantly promoted cell chemoresistance by regulating
      ATP-binding cassette subfamily C member 1 through binding Let-7a. Taken together,
      our study demonstrates that ANRIL could act as a functional oncogene in CRC, as
      well as a potential therapeutic target to inhibit CRC chemoresistance.

PMID- 30279207
TI  - Specific expression of lncRNA RP13-650J16.1 and TCONS_00023979 in prostate
      cancer.
AB  - The aim of the present study was to explore the expression profile and the
      potential regulatory mechanism of two long non-coding RNAs (lncRNAs) (RP13
      650J16.1 and TCONS_00023979) in prostate cancer (PCa). Expression profile of
      lncRNAs in PCa and paracancerous tissues were investgated by the high-throughput
      gene chip technology. Specific siRNA of RP13-650J16.1 or TCONS_00023979 was
      transfected into DU145 cells. Then, the relative expression of RP13-650J16.1,
      receptor-associated coactivator 3 (RAC3), promyelocytic leukemia (PML), and
      TCONS_00023979 was detected by quantitative real-time PCR and Western blotting.
      MTT assay was used to detect the proliferation of DU145 cells. The migration
      ability of DU145 cells was measured by Transwell chambers. Single cell
      proliferation and clonogenic ability were detected by plate clone formation
      assay. RP13-650J16.1 and RAC3 expression was up-regulated, and TCONS_00023979 and
      PML expression was down-regulated in PCa tissues. Silencing RP13-650J16.1 could
      decrease RAC3 expression, and knockout of TCONS_00023979 also reduced PML
      expression. Moreover, the ability of proliferation, migration, and colony
      formation of DU145 cells was decreased after transfected with si-RP13-650J16.1,
      while these abilities were increased after transfected with si-TCONS_00023979.
      Collectively, our findings demonstrated that RP13-650J16.1 might be an oncogene
      and TCONS_00023979 might be an antioncogene in PCa.

PMID- 30279208
TI  - von Willebrand factor rescued by miR-24 inhibition facilitates the proliferation
      and migration of osteosarcoma cells in vitro.
AB  - von Willebrand factor (vWF) is a major procoagulant molecule that was shown to
      differentiate between metastatic and primary osteosarcoma (OS) tissues and
      associated with increased metastasis. However, its functional role in OS
      progression has been unclear yet. The expression profile of vWF and miR-24 in
      human OS tissues was characterized using immunofluorescence labeling and
      quantitative real-time PCR analysis. The interaction between miR-24 and vWF was
      identified by dual luciferase reporter assay. The effects of vWF and miR-24 on OS
      cells were assessed by cell proliferation, colony formation, and migration. The
      clinical significance of miR-24 in OS patients was analyzed using Kaplan-Meier
      analyses and Pearson's Chi-squared test. Here, we reported that the expression of
      vWF was significantly increased, but miR-24 was significantly decreased in OS
      tissues (n=84). vWF was further validated as the target of miR-24 in MG-63 and
      U2OS cells. miR-24 obviously suppressed the proliferation and migration of MG-63
      and U2OS cells. However, the migration-inhibiting activity of miR-24 was
      predominantly attenuated by vWF overexpression. Clinically, low miR-24 expression
      in human OS tissues was significantly associated with tumor metastasis and
      predicted a poor survival in OS patients. This work demonstrated that vWF, as a
      downstream effector of miR-24, played an important role in controlling OS cell
      progression. Target miR-24 or vWF, therefore, promises to be an effective
      biological target for OS treatment.

PMID- 30279210
TI  - A novel antimicrobial peptide, Ranatuerin-2PLx, showing therapeutic potential in
      inhibiting proliferation of cancer cells.
AB  - Antimicrobial peptides are a promising resource for developing novel antibiotic
      and even anticancer drugs. Here, a 28-mer polypeptide, Ranatuerin-2PLx (R2PLx),
      was identified from lyophilised skin secretions. The chemically synthetic
      replicates exhibited moderate and broadspectrum antimicrobial effect against
      various microorganisms including methicillin-resistant Staphylococcus aureus
      (MRSA, minimal inhibitory concentration = 256 uM). In addition, R2PLx was found
      to inhibit the proliferation of several tumour cells, especially showing more
      potent effect on prostate cancer cell, PC-3. The early cell apoptosis was
      observed in 6 h by Annexin V-FITC/propidium iodide staining, as well as the
      activation of Caspase-3 at 5 uM peptide concentration. R2PLx may therefore be
      promising for developing new therapeutic approach for cancer treatment. Moreover,
      the artificial deficiency of conserved rana-box loop or net positive charge in C
      terminal domain notably reduced the biological activities of the truncated and
      substituted isoforms, respectively, suggesting for maintaining their biological
      potency of ranatuerin family requires both cysteine-bridged segment and
      cationincity within the loop domain in C-terminus.

PMID- 30279211
TI  - Lifetime risk of common neurological diseases in the elderly population.
AB  - OBJECTIVE: To quantify the burden of common neurological disease in older adults
      in terms of lifetime risks, including their co-occurrence and preventive
      potential, within a competing risk framework. METHODS: Within the prospective
      population-based Rotterdam Study, we studied lifetime risk of dementia, stroke
      and parkinsonism between 1990 and 2016. Among 12 102 individuals (57.7% women)
      aged >=45 years free from these diseases at baseline, we studied co-occurrence,
      and quantified the combined, and disease-specific remaining lifetime risk of
      these diseases at various ages for men and women separately. We also projected
      effects on lifetime risk of hypothetical preventive strategies that delay disease
      onset by 1, 2 and 3 years, respectively. RESULTS: During follow-up of up to 26
      years (156 088 person-years of follow-up), 1489 individuals were diagnosed with
      dementia, 1285 with stroke and 263 with parkinsonism. Of these individuals, 438
      (14.6%) were diagnosed with multiple diseases. Women were almost twice as likely
      as men to be diagnosed with both stroke and dementia during their lifetime. The
      lifetime risk for any of these diseases at age 45 was 48.2% (95% CI 47.1% to
      51.5%) in women and 36.2% (35.1% to 39.3%) in men. This difference was driven by
      a higher risk of dementia as the first manifesting disease in women than in men
      (25.9% vs 13.7%; p<0.001), while this was similar for stroke (19.0%vs18.9% in
      men) and parkinsonism (3.3% vs 3.6% in men). Preventive strategies that delay
      disease onset with 1 to 3 years could theoretically reduce lifetime risk for
      developing any of these diseases by 20%-50%. CONCLUSION: One in two women and one
      in three men will develop dementia, stroke or parkinsonism during their life.
      These findings strengthen the call for prioritising the focus on preventive
      interventions at population level which could substantially reduce the burden of
      common neurological diseases in the ageing population.

PMID- 30279212
TI  - Effects of vitamin D3 supplementation on cognition and blood lipids: a 12-month
      randomised, double-blind, placebo-controlled trial.

PMID- 30279209
TI  - The potential roles of circRNAs in osteoarthritis: a coming journey to find a
      treasure.
AB  - Osteoarthritis (OA), a common joint disease in elderly, causes serious social and
      economic burdens worldwide. Previous studies indicated that some differentially
      expressed circular RNAs (circRNAs) participated in the initiation and progression
      of OA. These findings suggested that circRNAs may act as promising diagnostic
      biomarkers and therapeutic targets for OA. In this review, we summarize the
      biogenesis and biological functions of circRNAs and explore the underlying roles
      of circRNAs in OA, which may enlighten further studies and contribute to the
      early diagnosis and intervention of OA.

PMID- 30279213
TI  - Proposal of new clinical diagnostic criteria for POEMS syndrome.
AB  - OBJECTIVE: To propose the optimal diagnostic criteria for polyneuropathy,
      organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome using
      appropriate statistical methods and disease controls. METHODS: This retrospective
      cohort study included 104 consecutive patients with suspected POEMS syndrome,
      among whom a gold standard group of 60 patients with definitive POEMS syndrome
      diagnosis were followed for at least 12 months to strictly exclude other
      disorders mimicking POEMS syndrome and to confirm response to POEMS syndrome
      specific treatment. Thirty patients with chronic inflammatory demyelinating
      polyradiculoneuropathy (demyelinating polyradiculoneuropathy controls) and 30
      with multiple myeloma or immunoglobulin light chain amyloidosis (monoclonal
      plasma cell proliferation controls) were also included. Logistic regression
      analyses were performed to determine optimal combination of clinical and
      laboratory abnormalities, characteristic of POEMS syndrome. RESULTS: The
      diagnostic criteria were statistically defined as the presence of the three major
      criteria (polyneuropathy (typically demyelinating), monoclonal plasma cell
      proliferative disorder and elevated vascular endothelial growth factor) and at
      least two of the four minor criteria (oedema/effusion, skin changes, organomegaly
      and sclerotic bone lesions), based on best performance by area under the receiver
      operating characteristic curve analyses. The sensitivity and specificity were
      100% and 100%, respectively; the diagnostic accuracy of the proposed criteria was
      equivalent to somewhat complicated previous criteria. CONCLUSIONS: The
      statistically defined, simple diagnostic criteria for POEMS syndrome could
      accelerate early diagnosis and treatment, thereby contribute to better outcome in
      patients with this serious disease. Prospective larger studies are required to
      confirm the validity.

PMID- 30279214
TI  - Vitamin D3 as a potentially modifiable factor in mild cognitive impairment.

PMID- 30279215
TI  - Trusting the experience of the experienced athlete.

PMID- 30279216
TI  - Creating the dream team: introducing participatory sports and exercise medicine
      via 'Patient Voices'.

PMID- 30279217
TI  - Temporal trends and regional variation in the rate of arthroscopic knee surgery
      in England: analysis of over 1.7 million procedures between 1997 and 2017. Has
      practice changed in response to new evidence?
AB  - OBJECTIVES: We investigated trends and regional variation in the rate of
      arthroscopic knee surgery performed in England from 1997-1998 to 2016-2017.
      DESIGN: Cross-sectional study of the national hospital episode statistics (HES)
      for England. METHODS: All hospital episodes for patients undergoing a knee
      arthroscopy between 1 April 1997 and 31 March 2017 were extracted from HES by
      procedure code. Age and sex-standardised rates of surgery were calculated using
      Office for National Statistic population data as the denominator. Trends in the
      rate of surgery were analysed by procedure both nationally and by Clinical
      Commissioning Group (CCG). RESULTS: A total of 1 088 872 arthroscopic partial
      meniscectomies (APMs), 326 600 diagnostic arthroscopies, 308 618 knee washouts
      and 252 885 chondroplasties were identified (1 759 467 hospital admissions; 1 447
      142 patients). The rate of APM increased from a low of 51/100 000 population (95%
      CI 51 to 52) in 1997-1998 to a peak at 149/100 000 (95% CI 148 to 150) in 2013
      2014; then, after 2014-2015, rates declined to 120/100 000 (95% CI 119 to 121) in
      2016-2017. Rates of arthroscopic knee washout and diagnostic arthroscopy declined
      steadily from 50/100 000 (95% CI 49 to 50) and 47/100 000 (95% CI 46 to 47)
      respectively in 1997-1998, to 4.8/100 000 (95% CI 4.6 to 5.0) and 8.1/100 000
      (95% CI 7.9 to 8.3) in 2016-2017. Rates of chondroplasty have increased from a
      low of 3.2/100 000 (95% CI 3.0 to 3.3) in 1997-1998 to 51/100 000 (95% CI 50.6 to
      51.7) in 2016-2017. Substantial regional and age-group variation in practice was
      detected. In 2016-2017, between 11% (22/207) and 16% (34/207) of CCGs performed
      at least double the national average rate of each procedure. CONCLUSIONS: Over
      the last 20 years, and likely in response to new evidence, rates of arthroscopic
      knee washout and diagnostic arthroscopy have declined by up to 90%. APM rates
      increased about 130% overall but have declined recently. Rates of chondroplasty
      increased about 15-fold. There is significant variation in practice, but the
      appropriate population intervention rate for these procedures remains unknown.

PMID- 30279218
TI  - First, do "nothing"... and listen.

PMID- 30279219
TI  - Effects of the '11+ Kids' injury prevention programme on severe injuries in
      children's football: a secondary analysis of data from a multicentre cluster
      randomised controlled trial.
AB  - BACKGROUND: To assess the effects of the injury prevention programme '11+ Kids'
      on reducing severe injuries in 7 to 13 year old football (soccer) players.
      METHODS: Football clubs (under-9, under-11 and under-13 age groups) from the
      Czech Republic, Germany, the Netherlands and Switzerland were cluster-randomised
      (clubs) into an intervention (INT) and a control group (CON). INT replaced their
      usual warm-up by '11+ Kids' two times a week. CON followed their regular training
      regime. Match and training exposure and injury characteristics were recorded and
      injury incidence rates (IRs) and 95% CIs calculated. For the present analysis,
      only severe injuries (absence from training/match >=28 days) were considered.
      Hazard ratios (HR) were calculated using extended Cox models. RESULTS: The
      overall IR of severe injuries per 1000 football hours was 0.33 (95% CI 0.25 to
      0.43) in CON and 0.15 (95% CI 0.10 to 0.23) in INT. There was a reduction of
      severe overall (HR 0.42, 95% CI 0.24 to 0.72), match (0.41, 0.17 to 0.95) and
      training injuries (0.42, 0.21 to 0.86) in INT. The injury types that were
      prevented the most were: other bone injuries 66%, fractures 49% and sprains and
      ligament injuries 37%. Severe injuries located at the knee (82%), hip/groin
      (81%), the foot/toe (80%) and the ankle (65%) were reduced tremendously.
      CONCLUSIONS: '11+ Kids' has a large preventive effect on severe injuries by
      investing only 15 to 20 min per training session. The present results should
      motivate coaches to implement effective injury prevention programmes such as the
      '11+ Kids' in children's football. TRIAL REGISTRATION NUMBER: NCT02222025.

PMID- 30279221
TI  - ATP binding cassette family A protein 1 determines hexosylceramide and
      sphingomyelin levels in human and mouse plasma.
AB  - Sphingolipids, including ceramide, SM, and hexosylceramide (HxCer), are carried
      in the plasma by lipoproteins. They are possible markers of metabolic diseases,
      but little is known about their control. We previously showed that microsomal
      triglyceride transfer protein (MTP) is critical to determine plasma ceramide and
      SM, but not HxCer, levels. In human plasma and mouse models, we examined possible
      HxCer-modulating pathways, including the role of ABCA1 in determining
      sphingolipid plasma concentrations. Compared with control samples, plasma from
      patients with Tangier disease (deficient in ABCA1) had significantly lower HxCer
      (-69%) and SM (-40%) levels. Similarly, mice deficient in hepatic and intestinal
      ABCA1 had significantly reduced HxCer (-79%) and SM (-85%) levels. Tissue
      specific ablation studies revealed that hepatic ABCA1 determines plasma HxCer and
      SM levels; that ablation of MTP and ABCA1 in the liver and intestine reduces
      plasma HxCer, SM, and ceramide levels; and that hepatic and intestinal MTP
      contribute to plasma ceramide levels, whereas only hepatic MTP modulates plasma
      SM levels. These results identify the contribution of ABCA1 to plasma SM and
      HxCer levels and suggest that MTP and ABCA1 are critical determinants of plasma
      sphingolipid levels.

PMID- 30279223
TI  - Five minutes with . . . Ramani Moonesinghe on the Fitter Better Sooner campaign.

PMID- 30279222
TI  - Comprehensive shotgun lipidomics of human meibomian gland secretions using
      MS/MSall with successive switching between acquisition polarity modes.
AB  - The lipid composition of human meibomian gland secretions (meibum) has been
      analyzed using both targeted and untargeted mass spectrometric approaches, each
      of which has its advantages and disadvantages. Herein we report the results of
      shotgun lipidomic profiling of human meibum using a new approach that combines
      the advantages of targeted and untargeted analyses to yield highly sensitive and
      comprehensive profiles. Samples containing an estimated 7-13 ug (8-16 nL) of
      human meibum lipids were analyzed using MS/MSall, an untargeted approach for
      MS/MS. Using MS/MSall with ESI and successive polarity switching, we obtained
      tandem mass spectra in both modes at every 1 Da step for all ions in the m/z 200
      1,200 range. In approximately 12 min, a total of 2 MS spectra and 2,000 MS/MS
      spectra were acquired for each sample, from which targeted analysis information
      was extracted. This approach allowed for the comprehensive and highly sensitive
      detection of meibum lipids, including species low in abundance. Altogether, more
      than 600 unique lipid molecular species were identified in meibum, 3 times more
      than previously reported in untargeted analyses of meibum samples. This
      untargeted MS and MS/MSall approach may be extended to other biological systems
      for the detection of lipids with sensitivity comparable to targeted analysis.

PMID- 30279220
TI  - Distinguishing the differences in beta-glycosylceramidase folds, dynamics, and
      actions informs therapeutic uses.
AB  - Glycosyl hydrolases (GHs) are carbohydrate-active enzymes that hydrolyze a
      specific beta-glycosidic bond in glycoconjugate substrates; beta-glucosidases
      degrade glucosylceramide, a ubiquitous glycosphingolipid. GHs are grouped into
      structurally similar families that themselves can be grouped into clans. GH1,
      GH5, and GH30 glycosidases belong to clan A hydrolases with a catalytic
      (beta/alpha)8 TIM barrel domain, whereas GH116 belongs to clan O with a catalytic
      (alpha/alpha)6 domain. In humans, GH abnormalities underlie metabolic diseases.
      The lysosomal enzyme glucocerebrosidase (family GH30), deficient in Gaucher
      disease and implicated in Parkinson disease etiology, and the cytosol-facing
      membrane-bound glucosylceramidase (family GH116) remove the terminal glucose from
      the ceramide lipid moiety. Here, we compare enzyme differences in fold, action,
      dynamics, and catalytic domain stabilization by binding site occupancy. We also
      explore other glycosidases with reported glycosylceramidase activity, including
      human cytosolic beta-glucosidase, intestinal lactase-phlorizin hydrolase, and
      lysosomal galactosylceramidase. Last, we describe the successful translation of
      research to practice: recombinant glycosidases and glucosylceramide metabolism
      modulators are approved drug products (enzyme replacement therapies). Activity
      based probes now facilitate the diagnosis of enzyme deficiency and screening for
      compounds that interact with the catalytic pocket of glycosidases. Future
      research may deepen the understanding of the functional variety of these enzymes
      and their therapeutic potential.

PMID- 30279224
TI  - Chromatin conformation and transcriptional activity are permissive regulators of
      DNA replication initiation in Drosophila.
AB  - Chromatin structure has emerged as a key contributor to spatial and temporal
      control over the initiation of DNA replication. However, despite genome-wide
      correlations between early replication of gene-rich, accessible euchromatin and
      late replication of gene-poor, inaccessible heterochromatin, a causal
      relationship between chromatin structure and replication initiation remains
      elusive. Here, we combined histone gene engineering and whole-genome sequencing
      in Drosophila to determine how perturbing chromatin structure affects replication
      initiation. We found that most pericentric heterochromatin remains late
      replicating in H3K9R mutants, even though H3K9R pericentric heterochromatin is
      depleted of HP1a, more accessible, and transcriptionally active. These data
      indicate that HP1a loss, increased chromatin accessibility, and elevated
      transcription do not result in early replication of heterochromatin.
      Nevertheless, a small amount of pericentric heterochromatin with increased
      accessibility replicates earlier in H3K9R mutants. Transcription is de-repressed
      in these regions of advanced replication but not in those regions of the H3K9R
      mutant genome that replicate later, suggesting that transcriptional repression
      may contribute to late replication. We also explored relationships among
      chromatin, transcription, and replication in euchromatin by analyzing H4K16R
      mutants. In Drosophila, the X Chromosome gene expression is up-regulated twofold
      and replicates earlier in XY males than it does in XX females. We found that
      H4K16R mutation prevents normal male development and abrogates hyperexpression
      and earlier replication of the male X, consistent with previously established
      genome-wide correlations between transcription and early replication. In
      contrast, H4K16R females are viable and fertile, indicating that H4K16
      modification is dispensable for genome replication and gene expression.

PMID- 30279225
TI  - The class I myosin MYO1D binds to lipid and protects against colitis.
AB  - Myosin ID (MYO1D) is a member of the class I myosin family. We screened 48,649
      third generation (G3) germline mutant mice derived from N-ethyl-N-nitrosourea
      mutagenized grandsires for intestinal homeostasis abnormalities after oral
      administration of dextran sodium sulfate (DSS). We found and validated mutations
      in Myo1d as a cause of increased susceptibility to DSS-induced colitis. MYO1D is
      produced in the intestinal epithelium, and the colitis phenotype is dependent on
      the nonhematopoietic compartment of the mouse. Moreover, MYO1D appears to couple
      cytoskeletal elements to lipid in an ATP-dependent manner. These findings
      demonstrate that MYO1D is needed to maintain epithelial integrity and protect
      against DSS-induced colitis.

PMID- 30279226
TI  - Small-molecule BCL6 inhibitor effectively treats mice with non-sclerodermatous
      chronic graft-versus-host disease.
AB  - Patient outcomes for steroid-dependent or -refractory cGVHD are poor and only
      ibrutinib has been FDA approved for this indication. cGVHD is often driven by the
      germinal center (GC) reaction, in which T follicular helper cells interact with
      GC B-cells to produce antibodies that are associated with disease pathogenesis.
      The transcriptional co-repressor BCL6 is a member of the BTB/POZ transcription
      factor family and master regulator of the immune cells in the GC reaction. We
      demonstrate that BCL6 expression in both donor T-cells and B-cells is necessary
      for cGVHD development, pointing to BCL6 as a therapeutic cGVHD target. A small
      molecule BCL6 inhibitor reversed active cGVHD in a mouse model of multi-organ
      system injury with bronchiolitis obliterans associated with a robust GC reaction
      but not in cGVHD mice with scleroderma as the prominent manifestation. For cGVHD
      patients with antibody-driven cGVHD, targeting of BCL6 represents a new approach
      with specificity for a master GC regulator that would extend the currently
      available second-line agents.

PMID- 30279227
TI  - Treatment with 5-azacytidine induces a sustained response in patients with
      angioimmunoblastic T-cell lymphoma.

PMID- 30279228
TI  - Blebbistatin modulates prostatic cell growth and contrapctility through myosin II
      signaling.
AB  - To investigate the effect of blebbistatin (BLEB, a selective myosin inhibitor) on
      regulating contractility and growth of prostate cells and to provide insight into
      possible mechanisms associated with these actions. BLEB was incubated with cell
      lines of BPH-1 and WPMY-1, and intraprostatically injected into rats. Cell growth
      was determined by flow cytometry, and in vitro organ bath studies were performed
      to explore muscle contractility. Smooth muscle (SM) myosin isoform (SM1/2, SM
      A/B, and LC17a/b) expression was determined via competitive reverse transcriptase
      PCR. SM myosin heavy chain (MHC), non-muscle (NM) MHC isoforms (NMMHC-A and NMMHC
      B), and proteins related to cell apoptosis were further analyzed via Western
      blotting. Masson's trichrome staining was applied to tissue sections. BLEB could
      dose-dependently trigger apoptosis and retard the growth of BPH-1 and WPMY-1.
      Consistent with in vitro effect, administration of BLEB to the prostate could
      decrease rat prostatic epithelial and SM cells via increased apoptosis. Western
      blotting confirmed the effects of BLEB on inducing apoptosis through a mechanism
      involving MLC20 dephosphorylation with down-regulation of Bcl-2 and up-regulation
      of BAX and cleaved caspase 3. Meanwhile, NMMHC-A and NMMHC-B, the downstream
      proteins of MLC20, were found significantly attenuated in BPH-1 and WPMY-1 cells,
      as well as rat prostate tissues. Additionally, BLEB decreased SM cell number and
      SM MHC expression, along with attenuated phenylephrine-induced contraction and
      altered prostate SMM isoform composition with up-regulation of SM-B and down
      regulation of LC17a, favoring a faster contraction. Our novel data demonstrate
      BLEB regulated myosin expression and functional activity. The mechanism involved
      MLC20 dephosphorylation and altered SMM isoform composition.

PMID- 30279229
TI  - Gene Expression Profiling Reveals Aberrant T-cell Marker Expression on Tumor
      Cells of Waldenstrom's Macroglobulinemia.
AB  - Purpose: That the malignant clone of Waldenstrom's macroglobulinemia (WM)
      demonstrates significant intraclonal heterogeneity with respect to plasmacytoid
      differentiation indicates the mechanistic complexity of tumorigenesis and
      progression. Identification of WM genes by comparing different stages of B cells
      may provide novel druggable targets.Experimental Design: The gene expression
      signatures of CD19+ B cells (BC) and CD138+ plasma cells (PC) from 19 patients
      with WM were compared with those of BCs from peripheral blood and tonsil and to
      those of PCs from the marrow of healthy (N-PC) and multiple myeloma donors (MM
      PC), as well as tonsil (T-PC). Flow cytometry and immunofluorescence were used to
      examine T-cell marker expression on WM tumor cells.Results: Consistent with
      defective differentiation, both BCs and PCs from WM cases expressed abnormal
      differentiation markers. Sets of 55 and 46 genes were differentially expressed in
      WM-BC and WM-PC, respectively; and 40 genes uniquely dysregulated in WM samples
      were identified. Dysregulated genes included cytokines, growth factor receptors,
      and oncogenes not previously implicated in WM or other plasma cell dyscrasias.
      Interestingly, strong upregulation of both IL6 and IL6R was confirmed. Supervised
      cluster analysis of PC revealed that marrow-derived WM-PC was either MM-PC-like
      or T-PC-like, but not N-PC-like. The aberrant expression of T-cell markers was
      confirmed at the protein level in WM-BC.Conclusions: We showed that comparative
      microarray profiles allowed gaining more comprehensive insights into the biology
      of WM. The data presented here have implications for the development of novel
      therapies, such as targeting aberrant T-cell markers in WM. Clin Cancer Res; 1-9.
      (c)2018 AACR.

PMID- 30279230
TI  - Fusion Kinases Identified by Genomic Analyses of Sporadic Microsatellite
      Instability-High Colorectal Cancers.
AB  - Purpose: Colorectal cancers with microsatellite instability-high (MSI-H) status,
      due to mismatch repair deficiency, are associated with poor patient outcomes
      after relapse. We aimed to identify novel therapeutic targets for
      them.Experimental Design: We performed MSI analyses of over 2,800 surgically
      resected colorectal tumors obtained from consecutive patients treated in Japan
      from 1998 through June 2016. Whole-exome sequencing, transcriptome sequencing,
      and methylation analyses were performed on 149 of 162 tumors showing MSI in BAT25
      and BAT26 loci. We analyzed patient survival times using Bonferroni-adjusted log
      rank tests.Results: Sporadic MSI-H colorectal cancers with promoter methylation
      of MLH1 (called MM) had a clinicopathological profile that was distinct from that
      of colorectal cancers of patients with germline mutations (Lynch syndrome, LS
      associated) or somatic, Lynch-like mutations in mismatch repair genes. MM tumors
      had more insertions and deletions and more recurrent mutations in BRAF and RNF43
      than LS-associated or Lynch-like MSI-H tumors. Eleven fusion kinases were
      exclusively detected in MM MSI-H colorectal cancers lacking oncogenic KRAS/BRAF
      missense mutations and were associated with worse post-relapse prognosis. We
      developed a simple method to identify MM tumors and applied it to a validation
      cohort of 28 MSI-H colorectal cancers, identifying 16 MM tumors and 2 fusion
      kinases.Conclusions: We discovered that fusion kinases are frequently observed
      among sporadic MM MSI-H colorectal cancers. The new method to identify MM tumors
      enables us to straightforwardly group MSI-H patients into candidates of LS or
      fusion kinase carriers. Clin Cancer Res; 1-12. (c)2018 AACR.

PMID- 30279231
TI  - Loss of RBMS3 Confers Platinum-resistance in Epithelial Ovarian Cancer via
      Activation of miR-126-5p/beta-catenin/CBP signaling.
AB  - PURPOSE: The development of resistance to platinum-based chemotherapy remains the
      unsurmountable obstacle in cancer treatment and consequently leads to tumor
      relapse. This study aims to investigate the mechanism by which loss of RBMS3
      induced chemoresistance in epithelial ovarian cancer (EOC). EXPERIMENTAL DESIGN:
      Fluorescence in situ hybridization and immunochemistry were used to determine
      deletion frequency and expression of RBMS3 in 15 clinical EOC tissues and 150
      clinicopathologically characterized EOC specimens. The effects of RBMS3 deletion
      and CBP/beta-catenin antagonist PRI-724 in chemoresistance were examined by clone
      formation and Annexin V assays in vitro, and by intraperitoneal tumor model in
      vivo The mechanism by which RBMS3 loss sustained activation of miR-126-5p/beta
      catenin/CBP signaling and the effects of RBMS3 and miR-126-5p competitively
      regulating DKK3, AXIN1, BACH1 and NFAT5 was explored using CLIP-seq, RIP,
      electrophoretic mobility shift and immunoblotting immunofluorescence assays.
      RESULTS: Loss of RBMS3 in EOC was correlated with the overall and relapse-free
      survival. Genetic ablation of RBMS3 significantly enhanced, whereas restoration
      of RBMS3 reduced, the chemoresistance ability of EOC cells both in vitro and in
      vivo RBMS3 inhibited beta-catenin/CBP signaling through directly associating with
      and stabilizing multiple negative regulators, including DKK3, AXIN1, BACH1 and
      NFAT5, via competitively preventing the miR-126-5p-mediated repression of these
      transcripts. Importantly, co-therapy of CBP/beta-catenin antagonist PRI-724
      induced sensitization of RBMS3-deleted EOC to platinum therapy. CONCLUSIONS: Our
      results demonstrate that genetic ablation of RBMS3 contributes to chemoresistance
      and PRI-724 may serve as a potential tailored treatment for patients with RBMS3
      deleted EOC.

PMID- 30279232
TI  - Arming an Oncolytic Herpes Simplex Virus Type 1 with a Single-chain Fragment
      Variable Antibody against PD-1 for Experimental Glioblastoma Therapy.
AB  - Purpose: Glioblastoma (GBM) is resistant to standard of care. Immune checkpoints
      inhibitors (such as anti-PD-1 mAbs) efficiently restore antitumor T-cell
      activity. We engineered a new oncolytic herpes simplex virus (oHSV) expressing a
      single-chain antibody against PD-1 (scFvPD-1) to evaluate its efficacy in mouse
      models of GBM.Experimental Design: NG34scFvPD-1 expresses the human GADD34 gene
      transcriptionally controlled by the Nestin promoter to allow replication in GBM
      cells and a scFvPD-1 cDNA transcriptionally controlled by the CMV promoter. ELISA
      assays were performed to detect binding of scFvPD-1 to mouse and human PD-1. In
      vitro cytotoxicity and replication assays were performed to measure NG34scFvPD-1
      oncolysis, and scFvPD-1 expression and secretion were determined. In vivo
      survival studies using orthotopic mouse GBM models were performed to evaluate the
      therapeutic potency of NG34scFvPD-1.Results: NG34scFvPD-1-infected GBM cells
      express and secrete scFvPD-1 that binds mouse PD-1. The introduction of the
      scFvPD-1 sequence in the viral backbone does not alter the oncolytic properties
      of NG34scFvPD-1. In situ NG34scFvPD-1 treatment improved the survival with a tail
      of durable survivorship in 2 syngeneic immunocompetent mouse models of GBM. Mice
      that survived the first GBM challenge rejected the second challenge of GBM when
      implanted in the contralateral hemisphere. However, this was not true when
      athymic mice were employed as the recipients of the second challenge, consistent
      with the need for an intact immune system to obtain a memory
      response.Conclusions: NG34scFvPD-1 treatment induces a durable antitumor response
      in 2 preclinical mouse models of GBM with evidence for antitumor memory. Clin
      Cancer Res; 1-10. (c)2018 AACR.

PMID- 30279234
TI  - Create new posts to ease newly qualified GPs into partnerships, review says.

PMID- 30279233
TI  - A Phase I/II Study of Evofosfamide, A Hypoxia-activated Prodrug with or without
      Bortezomib in Subjects with Relapsed/Refractory Multiple Myeloma.
AB  - Purpose: The presence of hypoxia in the diseased bone marrow presents a new
      therapeutic target for multiple myeloma. Evofosfamide (formerly TH-302) is a 2
      nitroimidazole prodrug of the DNA alkylator, bromo-isophosphoramide mustard,
      which is selectively activated under hypoxia. This trial was designed as a phase
      I/II study investigating evofosfamide in combination with dexamethasone, and in
      combination with bortezomib and dexamethasone in relapsed/refractory multiple
      myeloma.Experimental Design: Fifty-nine patients initiated therapy, 31 received
      the combination of evofosfamide and dexamethasone, and 28 received the
      combination of evofosfamide, bortezomib, and dexamethasone. Patients were heavily
      pretreated with a median number of prior therapies of 7 (range: 2-15). All had
      previously received bortezomib and immunomodulators. The MTD, treatment toxicity,
      and efficacy were determined.Results: The MTD was established at 340 mg/m2
      evofosfamide + dexamethasone with dose-limiting mucositis at higher doses. For
      the combination of evofosfamide, bortezomib, and dexamethasone, no patient had a
      dose-limiting toxicity (DLT) and the recommended phase II dose was established at
      340 mg/m2 The most common >=grade 3 adverse events (AE) were thrombocytopenia (25
      patients), anemia (24 patients), neutropenia (15 patients), and leukopenia (9
      patients). Skin toxicity was reported in 42 (71%) patients. Responses included 1
      very good partial response (VGPR), 3 partial response (PR), 2 minor response
      (MR), 20 stable disease (SD), and 4 progressive disease (PD) for evofosfamide +
      dexamethasone and 1 complete response (CR), 2 PR, 1 MR, 18 SD, and 5 PD for
      evofosfamide + bortezomib + dexamethasone. Disease stabilization was observed in
      over 80% and this was reflective of the prolonged overall survival of 11.2
      months.Conclusions: Evofosfamide can be administered at 340 mg/m2 twice a week
      with or without bortezomib. Clinical activity has been noted in patients with
      heavily pretreated relapsed refractory multiple myeloma. Clin Cancer Res; 1-9.
      (c)2018 AACR.

PMID- 30279235
TI  - Open label placebo: can honestly prescribed placebos evoke meaningful therapeutic
      benefits?

PMID- 30279236
TI  - Should Foreigners Get Costly Lifesaving Treatments in the United States?
AB  - Many foreign parents bring their children to the United States for medical
      treatments that are unavailable in their own country. Often, however, parents
      cannot afford expensive treatments. Doctors and hospitals then face a dilemma. Is
      it ethically permissible to consider the patient's citizenship and ability to
      pay? In this Ethics Rounds, we present a case in which a child from another
      country needs an expensive treatment. His parents cannot afford the treatment. He
      has come to a public hospital in the United States. We present responses from
      experts in pediatrics, bioethics, and health policy.

PMID- 30279237
TI  - Medicaid Expenditures Among Children With Noncomplex Chronic Diseases.
AB  - BACKGROUND AND OBJECTIVES: Expenditures for children with noncomplex chronic
      diseases (NC-CDs) are related to disease chronicity and resource use. The degree
      to which specific conditions contribute to high health care expenditures among
      children with NC-CDs is unknown. We sought to describe patient characteristics,
      expenditures, and use patterns of children with NC-CDs with the lowest (<=80th
      percentile), moderate (81-95th percentile), high (96-99th percentile), and the
      highest (>=99th percentile) expenditures. METHODS: In this retrospective cross
      sectional study, we used the 2014 Truven Medicaid MarketScan Database for claims
      from 11 states. We included continuously enrolled children (age <18 years) with
      NC-CDs (n = 1 563 233). We describe per member per year (PMPY) spending and use
      by each expenditure group for inpatient services, outpatient services, and the
      pharmacy for physical and mental health conditions. K-means clustering was used
      to identify expenditure types for the highest expenditure group. RESULTS:
      Medicaid PMPY spending ranged from $1466 (lowest expenditures) to $57 300
      (highest expenditures; P < .001); children in the highest expenditure group were
      diagnosed with a mental health condition twice as often (72.7% vs 34.1%). Cluster
      analysis was used to identify 3 distinct groups: 83% with high outpatient mental
      health expenditures (n = 13 033; median PMPY $18 814), 15% with high inpatient
      expenditures (n = 2386; median PMPY $92 950), and 1% with high pharmacy
      expenditures (n = 213; median $325 412). Mental health conditions accounted for
      half of the inpatient diagnoses in the cluster analysis. CONCLUSIONS: One percent
      of children with the highest expenditures accounted for 20% of Medicaid
      expenditures in children with NC-CDs; mental health conditions account for a
      large proportion of aggregate Medicaid spending in children with NC-CDs.

PMID- 30279239
TI  - Inner Workings: How fast is the universe expanding? Clashing measurements may
      point to new physics.

PMID- 30279238
TI  - The regenerating family member 3 beta instigates IL-17A-mediated neutrophil
      recruitment downstream of NOD1/2 signalling for controlling colonisation
      resistance independently of microbiota community structure.
AB  - OBJECTIVE: Loss of the Crohn's disease predisposing NOD2 gene results in an
      intestinal microenvironment conducive for colonisation by attaching-and-effacing
      enteropathogens. However, it remains elusive whether it relies on the
      intracellular recruitment of the serine-threonine kinase RIPK2 by NOD2, a step
      that is required for its activation of the transcription factor NF-kappaB.
      DESIGN: Colonisation resistance was evaluated in wild type and mutant mice, as
      well as in ex-germ-free (ex-GF) mice which were colonised either with faeces from
      Ripk2-deficient mice or with bacteria with similar preferences for carbohydrates
      to those acquired by the pathogen. The severity of the mucosal pathology was
      quantified at several time points postinfection by using a previously established
      scoring. The community resilience in response to infection was evaluated by 16S
      ribosomal RNA gene sequence analysis. The control of pathogen virulence was
      evaluated by monitoring the secretion of Citrobacter-specific antibody response
      in the faeces. RESULTS: Primary infection was similarly outcompeted in ex-GF
      Ripk2-deficient and control mice, demonstrating that the susceptibility to
      infection resulting from RIPK2 deficiency cannot be solely attributed to specific
      microbiota community structures. In contrast, delayed clearance of Citrobacter
      rodentium and exacerbated histopathology were preceded by a weakened propensity
      of intestinal macrophages to afford innate lymphoid cell activation. This tissue
      protection unexpectedly required the regenerating family member 3beta by
      instigating interleukin (IL) 17A-mediated neutrophil recruitment to the intestine
      and subsequent phosphorylation of signal transducer and activator of
      transcription 3. CONCLUSIONS: These results unveil a previously unrecognised
      mechanism that efficiently protects from colonisation by diarrhoeagenic bacteria
      early in infection.

PMID- 30279240
TI  - Core Concept: Perineuronal nets gain prominence for their role in learning,
      memory, and plasticity.

PMID- 30279242
TI  - HERC2 Facilitates BLM and WRN Helicase Complex Interaction with RPA to Suppress G
      Quadruplex DNA.
AB  - BLM and WRN are RecQ DNA helicasesessential for genomic stability. Here, we
      demonstrate that HERC2, a HECT E3 ligase, is critical for their functions to
      suppress G-quadruplex (G4) DNA. HERC2 interacted with BLM, WRN, and replication
      protein A (RPA) complexes during the S-phase of the cell cycle. Depletion of
      HERC2 dissociated RPA from BLM and WRN complexes and significantly increased G4
      formation. Triple depletion revealed that HERC2 has an epistatic relationship
      with BLM and WRN in their G4-suppressing function. In vitro, HERC2 released RPA
      onto single-stranded DNA (ssDNA) rather than anchoring onto RPA-coated ssDNA.
      CRISPR/Cas9-mediated deletion of the catalytic ubiquitin-binding site of HERC2
      inhibited ubiquitination of RPA2, caused RPA accumulation in the helicase
      complexes, and increased G4, indicating an essential role for E3 activity in the
      suppression of G4. Both depletion of HERC2 and inactivation of E3 sensitized
      cells to the G4-interacting compounds telomestatin and pyridostatin. Overall,
      these results indicate that HERC2 is a master regulator of G4 suppression that
      affects the sensitivity of cells to G4 stabilizers. Given that HERC2 expression
      is frequently reduced in many types of cancers, G4 accumulation as a result of
      HERC2 deficiency may provide a therapeutic target for G4
      stabilizers.Significance: HERC2 is revealed as a master regulator of G
      quadruplex, a DNA secondary structure that triggers genomic instability and may
      serve as a potential molecular target in cancer therapy.Graphical Abstract:
      http://cancerres.aacrjournals.org/content/canres/78/22/6371/F1.large.jpg Cancer
      Res; 78(22); 6371-85. (c)2018 AACR.

PMID- 30279243
TI  - 3D Deep Learning from CT Scans Predicts Tumor Invasiveness of Subcentimeter
      Pulmonary Adenocarcinomas.
AB  - Identification of early-stage pulmonary adenocarcinomas prior to surgery,
      especially in cases of sub-centimeter cancers, would be clinically important and
      could provide guidance to clinical decision making. In this study, we developed a
      deep learning system based on 3D convolutional neural networks and multi-task
      learning, which automatically predicts tumor invasiveness, together with 3D
      nodule segmentation masks. The system processes a 3D nodule-centered patch of pre
      processed CT and learns a deep representation of a given nodule without the need
      for any additional information. A dataset of 651 nodules with manually segmented
      voxel-wise masks and pathological labels of atypical adenomatous hyperplasia
      (AAH), adenocarcinomas in situ (AIS), minimally invasive adenocarcinoma (MIA),
      and invasive pulmonary adenocarcinoma (IA) was used in this study. We trained and
      validated our deep learning system on 523 nodules and tested its performance on
      128 nodules. An observer study with 2 groups of radiologists, 2 senior and 2
      junior, was also investigated. We merged AAH and AIS into one single category AAH
      AIS, comprising a 3-category classification in our study. The proposed deep
      learning system achieved better classification performance than the radiologists;
      in terms of 3-class weighted average F1 score, the model achieved 63.3% while the
      radiologists achieved 55.6%, 56.6%, 54.3%, and 51.0%, respectively. These results
      suggest that deep learning methods improve the yield of discriminative results
      and hold promise in the CADx application domain, which could help doctors work
      efficiently and facilitate the application of precision medicine.

PMID- 30279246
TI  - Not just another nursemaid's: an enigmatic paediatric humeral fracture.
AB  - In the medical literature, the discussion of radial head subluxation (RHS) and
      nursemaid's elbow may highlight the ability to diagnose and treat the injured
      patient without obtaining imaging studies. This case reiterates the importance of
      a thorough physical examination and the use of appropriate imaging when point
      tenderness is exposed in the injured limb. With point tenderness to the arm, a
      child with a presumed RHS, otherwise known as nursemaid's elbow, should be
      evaluated using radiographic imaging to prevent additional potentially
      destructive physical manipulation of the patient's upper extremity.

PMID- 30279244
TI  - A Novel Small-Molecule Inhibitor of MRCK Prevents Radiation-Driven Invasion in
      Glioblastoma.
AB  - Glioblastoma (GBM) is an aggressive and incurable primary brain tumor that causes
      severe neurologic, cognitive, and psychologic symptoms. Symptoms are caused and
      exacerbated by the infiltrative properties of GBM cells, which enable them to
      pervade the healthy brain and disrupt normal function. Recent research has
      indicated that although radiotherapy (RT) remains the most effective component of
      multimodality therapy for patients with GBM, it can provoke a more infiltrative
      phenotype in GBM cells that survive treatment. Here, we demonstrate an essential
      role of the actin-myosin regulatory kinase myotonic dystrophy kinase-related
      CDC42-binding kinase (MRCK) in mediating the proinvasive effects of radiation.
      MRCK-mediated invasion occurred via downstream signaling to effector molecules
      MYPT1 and MLC2. MRCK was activated by clinically relevant doses per fraction of
      radiation, and this activation was concomitant with an increase in GBM cell
      motility and invasion. Furthermore, ablation of MRCK activity either by RNAi or
      by inhibition with the novel small-molecule inhibitor BDP-9066 prevented
      radiation-driven increases in motility both in vitro and in a clinically relevant
      orthotopic xenograft model of GBM. Crucially, treatment with BDP-9066 in
      combination with RT significantly increased survival in this model and markedly
      reduced infiltration of the contralateral cerebral hemisphere.Significance: An
      effective new strategy for the treatment of glioblastoma uses a novel, anti
      invasive chemotherapeutic to prevent infiltration of the normal brain by
      glioblastoma cells.Cancer Res; 78(22); 6509-22. (c)2018 AACR.

PMID- 30279247
TI  - Autoimmune autonomic ganglionopathy associated with Sjogren's syndrome presenting
      with recurrent abdominal distension.
AB  - A 65-year-old woman with Sjogren's syndrome presented with recurrent abdominal
      distension, constipation, weight loss, orthostatic dizziness, loss of sweating
      and incomplete emptying of the bladder. Gastrointestinal dilatation but no
      evidence of malignancy or obstruction was found on CT of the abdomen,
      oesophagogastroduodenoscopy or colonoscopy. Postvoiding residual urine volume was
      increased. Antiganglionic acetylcholine receptor antibody was positive. We
      diagnosed as autoimmune autonomic ganglionopathy. The patient responded to
      corticosteroid treatment. One year after treatment, she continued to have mild
      gastrointestinal symptoms, but overall condition was stable without further
      intervention.

PMID- 30279248
TI  - Olmesartan-induced enteropathy.
AB  - Olmesartan-induced enteropathy (OIE) typically presents with a constellation of
      signs and symptoms including chronic diarrhoea, weight loss and villous atrophy
      on biopsy. We describe a 68-year-old Caucasian woman with a history of
      hypothyroidism and hypertension who presented to our hospital with recurrent
      episodes of acute intermittent diarrhoea, nausea, vomiting, renal failure and 15
      lbs weight loss. After an extensive workup, she was diagnosed with possible OIE.
      Cessation of the offending drug resulted in improvement of clinical symptoms and
      also hospital admissions for severe diarrhoea reinforcing the diagnosis of OIE.
      Among the adverse effects of drug therapy, diarrhoea is a relatively frequent
      adverse event accounting for about 7%. This report serves as an addition to
      existing literature and to increase the awareness of olmesartan-induced sprue
      like enteropathy among the primary care physicians and gastroenterologists.

PMID- 30279250
TI  - Unusual and rare case of generalised lymphadenopathy: Kimura's disease.
AB  - We report a case of Kimura's disease in a 65-year-old woman who presented with
      generalised itching, abdominal pain, facial puffiness, difficulty in swallowing
      and loss of appetite. She was found to have generalised lymphadenopathy and a
      fine-needle aspiration cytology initially done revealed 'reactive lymphadenitis'
      which was inconclusive. PET-CT done showed features suggestive of lymphoma.
      Hence, lymph node biopsy was done for confirmation and incidentally after
      immunohistochemistry staining it turned out to be Kimura's disease. High-dose
      steroid therapy was started and patient showed dramatic clinical and symptomatic
      improvement. Kimura's disease almost always presents as cervical lymphadenopathy
      and usually never causes compressive symptoms. Our patient presented with
      compressive symptoms and generalised lymphadenopathy which is a rarity.

PMID- 30279249
TI  - Miliary tuberculosis and herpes pharyngitis after a trip to a developing country:
      dangers of biologics.
AB  - The use of biologic drugs has expanded since its introduction in the late 1990s.
      With growing medical use and newer biologic drugs in development, opportunistic
      infections like Mycobacterium tuberculosis remain important adverse effects. It
      carries major public health concerns, yet evidence-based clinical guidelines for
      more routine interval screening in patients taking immunosuppressants and exposed
      to tuberculosis (TB) are lacking. We illustrate a case of an elderly Indian-born
      man living in the USA with psoriatic arthritis who was on adalimumab for 10
      years. He presented with disseminated TB and herpes simplex virus type 1 (HSV-1)
      pharyngitis, a year after an innocuous trip to India. Our case draws attention to
      the adverse effects of biologic drugs and highlights the importance of regular
      rescreening for a high-risk population. As the use of biologic treatment
      increases, physicians must be vigilant in more frequent screening, monitoring and
      identifying related opportunistic infections, notably M. tuberculosis infections.

PMID- 30279251
TI  - Dual ectopic thyroid gland.

PMID- 30279252
TI  - Beliefs and reality of e-cigarette smoking.
AB  - In this global health case study, we describe a case of nicotine addiction due to
      chronic use of electronic cigarettes (e-cigarette) and discuss the beliefs on
      safety and awareness of their side effects. Many people believe that smoking an e
      cigarette (vaping) does not have any side effects, especially among teenagers and
      young adults. Teenagers using an e-cigarette at a young age are twice as likely
      to try cigarettes later in their life because of nicotine dependency or other
      social factors. More recent studies have shown long-term systemic side effects of
      vaping regardless of traditional cigarette smoking history. This report was done
      for further assessing their risk and to clear out misconceptions of this large
      scale condition.

PMID- 30279253
TI  - Troubleshooting a dialysis line: when blue runs red.
AB  - We present the case of a critically ill woman whose dialysis line was noted to be
      circulating bright red blood. Located in the right internal jugular vein, the
      line had previously been working normally with the change occurring shortly after
      the patient was liberated from positive pressure mechanical ventilation. An
      arterial malposition was ruled out and subsequent investigations revealed the
      presence of a left-sided partial anomalous pulmonary venous connection (PAPVC)
      that had been previously undiagnosed. The identification of a left-sided PAPVC
      from blood gas measurements taken from a right internal jugular vein dialysis
      catheter in this case provides an informative opportunity to consider the
      intricate physiological relationship between the respiratory and cardiovascular
      systems in critically ill patients requiring invasive procedures and treatments.

PMID- 30279254
TI  - Diabetic ketoalkalosis: misnomer or undiagnosed variant of diabetic ketoacidosis.
AB  - Usually, hyperglycaemia crisis presents with acidotic pH, but ketoalkalosis is a
      rare and unheard entity presenting in diabetic ketoacidosis. We describe three
      unique cases where the patients present with hyperglycaemia >250 mg/dL, normal or
      alkalotic pH, and bicarbonate >20 meq/L, which does not meet criteria for
      diabetic ketoacidosis. However, once these patients were supplemented with
      intravenous fluids, diagnosis of diabetic ketoacidosis was evident in laboratory
      analysis. These case series provide a learning opportunity in diagnosing and
      management of this rare phenomenon.

PMID- 30279255
TI  - First-line ibrutinib for Bing-Neel syndrome.
AB  - The authors present a case of an elderly man with a history of Waldenstrom
      macroglobulinaemia in remission who presented with progressively worsening gait
      abnormalities and falls for several months. His examination was notable for
      bilateral lower extremity weakness and an unsteady gait. Brain and spinal MRI
      showed focal leptomeningeal enhancement in the brain and spinal column. Lumbar
      puncture was performed and cerebrospinal fluid flow cytometry demonstrated a
      monoclonal CD5/CD10-negative, CD20-positive B-cell lymphocyte population
      consistent with a diagnosis of Bing-Neel syndrome. He was started on ibrutinib,
      an oral Bruton's tyrosine kinase inhibitor, and had marked improvement in his
      weakness and gait. Repeat imaging 2 months after starting ibrutinib showed
      improvement in his leptomeningeal enhancement. During subsequent follow-up, he
      continued to tolerate ibrutinib and had a sustained clinical response.

PMID- 30279256
TI  - Giant right coronary artery aneurysm complicated by a fistula to the right
      atrium, mimicking a ruptured sinus of Valsalva aneurysm.
AB  - Patients with a coronary aneurysm alone do not generally exhibit continuous
      murmurs; however, murmurs may be detected in the presence of a fistula. A 57-year
      old woman with chest pain was referred to us with a suspected diagnosis of a
      ruptured sinus of Valsalva aneurysm owing to the presence of a continuous murmur
      that was detected on physical examination. However, CT revealed a giant right
      coronary artery aneurysm draining into the right atrium. Consequently, surgery
      was performed. This case highlights the importance of implementing multiple
      imaging modalities for adequate differential diagnoses of patients presenting
      with continuous murmurs.

PMID- 30279257
TI  - Spontaneous rupture of a pancreatic pseudocyst.

PMID- 30279258
TI  - Advancement of the Harrington technique for reconstruction of pathological
      fractures of the acetabulum.
AB  - A 59-year-old man presented with hip pain secondary to metastatic prostate
      carcinoma affecting multiple sites, including his left acetabulum. The patient's
      prognosis was good, he was active, independent, with a good quality of life, so
      was offered surgical reconstruction. The Harrington method involves passing metal
      rods from the ileum to the ischium and pubis to create a scaffold for hip
      replacement. This is the gold standard for reconstruction of acetabular
      metastatic defects. However, this method is prone to failure by medialisation of
      the construct in the long term. We present our technique of employing a novel
      modification to the Harrington reconstruction that offers additional support
      medially with a suprapectineal plate. This construct is strong and durable enough
      to facilitate immediate weight-bearing and prevent long-term medialisation.

PMID- 30279259
TI  - Ace the case: a 14-year-old with lower extremity weakness and blurry vision.

PMID- 30279260
TI  - Ehrlichiosis masquerading as thrombotic thrombocytopenic purpura.
AB  - Ehrlichiosis is a rare tickborne illness that can manifest from an asymptomatic,
      self-limiting disease to a severe presentation with encephalopathy and renal
      failure. Ehrlichiosis is diagnosed largely based on patient history with
      confirmatory tests including peripheral blood smear, serology and PCR. Empiric
      treatment is warranted in patients with suspected tick bites as a delay in
      treatment can result in multiorgan failure. We discuss a case of ehrlichiosis
      that presented with the classic pentad of thrombotic thrombocytopenic purpura
      (TTP). A history of a tick bite was elicited and intravenous doxycycline 100 mg
      two times a day was initiated. Tick panel results revealed a positive Ehrlichia
      chaffeensis IgG and IgM titres, consistent with human monocytic ehrlichiosis.
      Autoimmune workup and antibodies to Borreliaburgdorferi were negative, and
      ADAMTS13 activity assay results were inconsistent with TTP. The patient completed
      14 days of intravenous doxycycline and had an uneventful recovery.

PMID- 30279261
TI  - Haematometrocolpos due to transverse vaginal septum with distal atretic vagina.

PMID- 30279262
TI  - Pancake kidney: an incidental finding in a young man.

PMID- 30279263
TI  - Third-degree burns associated with transcutaneous pacing.
AB  - A 69-year-old severely obese diabetic woman developed nausea, vomiting and
      diarrhoea which caused multiple metabolic alterations leading to hypotension and
      bradycardia due to slow atrioventricular junctional rhythm. Transcutaneous pacing
      (TCP) was initiated and maintained until the underlying heart rate and blood
      pressure normalised. TCP gel pads were kept in place prophylactically after
      pacing was terminated. Gel pads remained attached to the anterior thorax and back
      for a total of 36 hours. During this time the patient developed third-degree
      burns at the side of gel pad attachment. With appropriate wound care and after a
      long hospitalisation, the patient was discharged in stable condition. This case
      demonstrates that prolonged use of TCP gel pads without frequent replacement may
      lead to third-degree burns. It also suggest that prophylactic use of TCP gel pads
      should be avoided.

PMID- 30279264
TI  - Case of pneumomediastinum due to alveolar rupture following endotracheal
      intubation.

PMID- 30279265
TI  - Saccular internal carotid artery aneurysm masquerading as a pituitary
      macroadenoma.

PMID- 30279266
TI  - Pigmentary retinopathy in Kearns-Sayre syndrome.

PMID- 30279267
TI  - Tocilizumab in patients with adult-onset still's disease refractory to
      glucocorticoid treatment: a randomised, double-blind, placebo-controlled phase
      III trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of tocilizumab, an interleukin-6
      receptor antibody, in patients with adult-onset Still's disease. METHODS: In this
      double-blind, randomised, placebo-controlled phase III trial, 27 patients with
      adult-onset Still's disease refractory to glucocorticoids were randomised to
      tocilizumab at a dose of 8 mg/kg or placebo given intravenously every 2 weeks
      during the 12-week, double-blind phase. Patients received open-label tocilizumab
      for 40 weeks subsequently. The primary outcome was American College of
      Rheumatology (ACR) 50 response at week 4. The secondary outcomes included ACR
      20/50/70, systemic feature score, glucocorticoid dose and adverse events at each
      point. RESULTS: In the full analysis set, ACR50 response at week 4 was achieved
      in 61.5% (95% CI 31.6 to 86.1) in the tocilizumab group and 30.8% (95% CI 9.1 to
      61.4) in the placebo group (p=0.24). The least squares means for change in
      systemic feature score at week 12 were -4.1 in the tocilizumab group and -2.3 in
      the placebo group (p=0.003). The dose of glucocorticoids at week 12 decreased by
      46.2% in the tocilizumab group and 21.0% in the placebo group (p=0.017). At week
      52, the rates of ACR20, ACR50 and ACR70 were 84.6%, 84.6% and 61.5%,
      respectively, in both groups. Serious adverse events in all participants who
      received one dose of tocilizumab were infections, aseptic necrosis in the hips,
      exacerbation of adult-onset Still's disease, drug eruption and anaphylactic
      shock. CONCLUSION: The study suggests that tocilizumab is effective in adult
      onset Still's disease, although the primary endpoint was not met and solid
      conclusion was not drawn.

PMID- 30279269
TI  - NF-kappaB-Responsive miRNA-31-5p elicits endothelial dysfunction associated with
      preeclampsia via downregulation of endothelial nitric oxide synthase.
AB  - Inflammatory cytokines, including TNF-alpha, were elevated in patients with
      cardiovascular diseases and are also considered as crucial factors in the
      pathogenesis of preeclampsia; however, the underlying pathogenic mechanism has
      not been clearly elucidated. The present study provides novel evidence that TNF
      alpha leads to endothelial dysfunction associated with hypertension and vascular
      remodeling in preeclampsia through downregulation of eNOS by NF-kappaB-dependent
      biogenesis of microRNA (miR)-31-5p, which targets eNOS mRNA. In this study, we
      found that miR-31-5p was upregulated in sera from patients with preeclampsia and
      in human endothelial cells treated with TNF-alpha. TNF-alpha-mediated induction
      of miR-31-5p was blocked by an NF-kappaB inhibitor and NF-kappaB p65 knockdown,
      but not by MAPK and PI3K inhibitors, indicating that NF-kappaB is essential for
      biogenesis of miR-31-5p. The treatment of human endothelial cells with TNF-alpha
      or miR-31-5p mimic decreased endothelial nitric oxide synthase (eNOS) mRNA
      stability without affecting eNOS promoter activity, resulting in inhibition of
      eNOS expression and NO/cGMP production through blocking of the functional
      activity of the eNOS mRNA 3'-untranslated region. Moreover, TNF-alpha and miR-31
      5p mimic evoked endothelial dysfunction associated with defects in angiogenesis,
      trophoblastic invasion, and vasorelaxation in an ex vivo cultured model of human
      placental arterial vessels, which are typical features of preeclampsia. These
      results suggest that NF-kappaB-responsive miR-31-5p elicits endothelial
      dysfunction, hypertension, and vascular remodeling via post-transcriptional
      downregulation of eNOS and is a molecular risk factor in the pathogenesis and
      development of preeclampsia.

PMID- 30279271
TI  - Leading US cancer hospital alters conflict of interest rules after controversies.

PMID- 30279270
TI  - Crystal structure of a human ubiquitin E1-ubiquitin complex reveals conserved
      functional elements essential for activity.
AB  - Ubiquitin (Ub) signaling plays a key regulatory role in nearly every aspect of
      eukaryotic biology and is initiated by E1 enzymes that activate and transfer Ub
      to E2 Ub-conjugating enzymes. Despite Ub E1's fundamental importance to the cell
      and its attractiveness as a target for therapeutic intervention in cancer and
      other diseases, its only available structural information is derived from yeast
      orthologs of human ubiquitin-like modifier-activating enzyme 1 (hUBA1). To
      illuminate structural differences between yeast and hUBA1 structures that might
      be exploited for the development of small-molecule therapeutics, we determined
      the first crystal structure of a hUBA1-Ub complex. Using structural analysis,
      molecular modeling, and biochemical analysis, we demonstrate that hUBA1 shares a
      conserved overall structure and mechanism with previously characterized yeast
      orthologs, but displays subtle structural differences, particularly within the
      active site. Computational analysis revealed four potential ligand-binding hot
      spots on the surface of hUBA1 that might serve as targets to inhibit hUBA1 at the
      level of Ub activation or E2 recruitment or that might potentially be used in
      approaches such as protein-targeting chimeric molecules. Taken together, our work
      enhances our understanding of the hUBA1 mechanism, provides an improved framework
      for the development of small-molecule inhibitors of UBA1, and serves as a
      stepping stone for structural studies that involve the enzymes of the human Ub
      system at the level of both E1 and E2.

PMID- 30279272
TI  - Inhibitory Anti-Peroxidasin Antibodies in Pulmonary-Renal Syndromes.
AB  - BACKGROUND: Goodpasture syndrome (GP) is a pulmonary-renal syndrome characterized
      by autoantibodies directed against the NC1 domains of collagen IV in the
      glomerular and alveolar basement membranes. Exposure of the cryptic epitope is
      thought to occur via disruption of sulfilimine crosslinks in the NC1 domain that
      are formed by peroxidasin-dependent production of hypobromous acid. Peroxidasin,
      a heme peroxidase, has significant structural overlap with myeloperoxidase (MPO),
      and MPO-ANCA is present both before and at GP diagnosis in some patients. We
      determined whether autoantibodies directed against peroxidasin are also detected
      in GP. METHODS: We used ELISA and competitive binding assays to assess the
      presence and specificity of autoantibodies in serum from patients with GP and
      healthy controls. Peroxidasin activity was fluorometrically measured in the
      presence of partially purified IgG from patients or controls. Clinical disease
      severity was gauged by Birmingham Vasculitis Activity Score. RESULTS: We detected
      anti-peroxidasin autoantibodies in the serum of patients with GP before and at
      clinical presentation. Enriched anti-peroxidasin antibodies inhibited peroxidasin
      mediated hypobromous acid production in vitro. The anti-peroxidasin antibodies
      recognized peroxidasin but not soluble MPO. However, these antibodies did
      crossreact with MPO coated on the polystyrene plates used for ELISAs. Finally,
      peroxidasin-specific antibodies were also found in serum from patients with anti
      MPO vasculitis and were associated with significantly more active clinical
      disease. CONCLUSIONS: Anti-peroxidasin antibodies, which would previously have
      been mischaracterized, are associated with pulmonary-renal syndromes, both before
      and during active disease, and may be involved in disease activity and
      pathogenesis in some patients.

PMID- 30279274
TI  - Translational Methods in Nephrology: Individual Treatment Effect Modeling.

PMID- 30279273
TI  - Dickkopf-3 (DKK3) in Urine Identifies Patients with Short-Term Risk of eGFR Loss.
AB  - BACKGROUND: The individual course of CKD may vary, and improved methods for
      identifying which patients will experience short-term eGFR loss are needed.
      Assessing urinary Dickkopf-3 (DKK3), a stress-induced tubular epithelia-derived
      profibrotic glycoprotein, may provide information about ongoing
      tubulointerstitial fibrosis and short-term eGFR loss. METHODS: To investigate
      urinary DKK3's potential as a biomarker of short-term eGFR loss (over 12 months),
      we prospectively assessed eGFR and urinary DKK3 levels in patients with CKD of
      various etiologies at baseline and annual follow-ups. We also measured urinary
      DKK3 in a general population sample and patients with diagnostic kidney biopsies
      or IgA nephropathy under treatment. RESULTS: Median urinary DKK3-to-creatinine
      concentration at baseline was significantly higher in patients with CKD than the
      general population sample (431 versus 33 pg/mg). In the CKD cohort, having a
      urinary DKK3-to-creatinine level >4000 pg/mg was independently and significantly
      associated after multiple adjustments with mean annual decline in eGFR of 7.6%
      over 12 months. Urinary DKK3 significantly improved prediction of kidney function
      decline compared with eGFR or albuminuria alone. Urinary DKK3-to-creatinine
      levels were related to the extent of tubulointerstitial fibrosis in kidney
      biopsies. In patients with IgA nephropathy, a rise in urinary DKK3 was associated
      with significant eGFR decline within 6 months, whereas stable or decreasing
      urinary DKK3 indicated a more favorable course. CONCLUSIONS: Urinary DKK3 levels
      identify patients at high risk for eGFR decline over the next 12 months
      regardless of the cause of kidney injury and beyond established biomarkers,
      potentially providing a tool to monitor CKD progression and assess effects of
      interventions.

PMID- 30279275
TI  - Savings Opportunity from Improved CKD Care Management.

PMID- 30279268
TI  - Impact of body mass index on the outcome of catheter ablation of atrial
      fibrillation.
AB  - OBJECTIVES: The association between obesity and atrial fibrillation (AF) is well
      established. We aimed to evaluate the impact of index body mass index (BMI) on AF
      recurrence at 12 months following catheter ablation using propensity-weighted
      analysis. In addition, periprocedural complications and fluoroscopy details were
      examined to assess overall safety in relationship to increasing BMI ranges.
      METHODS: Baseline, periprocedural and follow-up data were collected on
      consecutive patients scheduled for AF ablation. There were no specific exclusion
      criteria. Patients were categorised according to baseline BMI in order to assess
      the outcomes for each category. RESULTS: Among 3333 patients, 728 (21.8%) were
      classified as normal (BMI <25.0 kg/m2), 1537 (46.1%) as overweight (BMI 25.5-29.0
      kg/m2) and 1068 (32.0%) as obese (BMI >=30.0 kg/m2). Procedural duration and
      radiation dose were higher for overweight and obese patients compared with those
      with a normal BMI (p=0.002 and p<0.001, respectively). An index BMI >=30 kg/m2
      led to a 1.2-fold increased likelihood of experiencing recurrent AF at 12-months
      follow-up as compared with overweight patients (HR 1.223; 95% CI 1.047 to 1.429;
      p=0.011), while no significant correlation was found between overweight and
      normal BMI groups (HR 0.954; 95% CI 0.798 to 1.140; p=0.605) and obese versus
      normal BMI (HR 1.16; 95% CI 0.965 to 1.412; p=0.112). CONCLUSIONS: Patients with
      a baseline BMI >=30 kg/m2 have a higher recurrence rate of AF following catheter
      ablation and therefore lifestyle modification to target obesity preprocedure
      should be considered in these patients.

PMID- 30279277
TI  - Meeting the need for corrective spectacles in visually impaired Chinese school
      children: the potential of ready-made spectacles.
AB  - PURPOSE: To assess the potential of ready-made (spherical) spectacles (RMS) in
      meeting the need for refractive correction in visually impaired children in
      China. METHODS: Eligible children aged 5-17 years were identified from the three
      study sites in China. Distance visual acuity was measured with a retroilluminated
      logarithm of the minimum angle of resolution chart with tumbling E optotypes.
      Cycloplegic autorefraction was performed on all children using a handheld
      autorefractor. If uncorrected visual acuity (UCVA) was <=20/40 in either eye,
      best corrected visual acuity was measured with subjective refractive error.
      RESULTS : A total of 13 702 children were enumerated from the three studies, with
      12 334 (90.0%) having both reliable visual acuity measurements and successful
      cycloplegia. Among the 12 334 study children, the prevalence of UCVA <=20/40 in
      the better seeing eye was 16.4% (95% CI 15.0% to 17.8%), with 91.1% (1843) of
      these improving by >=3 lines of visual acuity with refractive correction.
      Prevalence was 12.7% (95% CI 11.5% to 13.9%) for UCVA <20/50 with 97.4% (1521)
      improving by >=3 lines, and 9.38% (95% CI 8.39% to 19.4%) for UCVA <=20/63 with
      98.4% (1138) improving by >=3 lines. Depending on the severity of visual
      impairment, 62.8%-64.0% of children could be accommodated with RMS if not
      correcting for astigmatism of <=0.75 dioptres and anisometropia of <=0.50
      spherical equivalent dioptres. Approximately 87% of children could be
      accommodated with RMS if astigmatism and anisometropia limits were increased to
      <=1.25 and <=1.50 dioptres, respectively. CONCLUSIONS: RMS could substantially
      alleviate visual morbidity in two-thirds or more of visually impaired
      schoolchildren in China. This cost-effective approach to refractive correction
      might also be useful in low/middle-income countries with poor access to
      optometric services.

PMID- 30279278
TI  - A Bosman ruling for science.

PMID- 30279276
TI  - Differential GAP requirement for Cdc42-GTP polarization during proliferation and
      sexual reproduction.
AB  - The formation of a local zone of Cdc42 GTPase activity, which governs cell
      polarization in many cell types, requires not only local activation but also
      switch-off mechanisms. In this study, we identify Rga3, a paralog of Rga4, as a
      novel Cdc42 GTPase-activating protein (GAP) in the fission yeast
      Schizosaccharomyces pombe Contrary to Rga4, Rga3 localizes with Cdc42-GTP to
      sites of polarity. Rga3 is dispensable for cell polarization during mitotic
      growth, but it limits the lifetime of unstable Cdc42-GTP patches that underlie
      cell pairing during sexual reproduction, masking a partly compensatory patch
      wandering motion. In consequence, cells lacking rga3 hyperpolarize and lose out
      in mating competition. Rga3 synergizes with the Cdc42 GAPs Rga4 and Rga6 to
      restrict Cdc42-GTP zone sizes during mitotic growth. Surprisingly, triple-mutant
      cells, which are almost fully round, retain pheromone-dependent dynamic
      polarization of Cdc42-GTP, extend a polarized projection, and mate. Thus, the
      requirement for Cdc42-GTP hydrolysis by GAPs is distinct during polarization by
      intrinsic or extrinsic cues.

PMID- 30279279
TI  - Co-inhibition of immunoproteasome subunits LMP2 and LMP7 is required to block
      autoimmunity.
AB  - Cells of hematopoietic origin express high levels of the immunoproteasome, a
      cytokine-inducible proteasome variant comprising the proteolytic subunits LMP2
      (beta1i), MECL-1 (beta2i), and LMP7 (beta5i). Targeting the immunoproteasome in
      pre-clinical models of autoimmune diseases with the epoxyketone inhibitor ONX
      0914 has proven to be effective. ONX 0914 was previously described as a selective
      LMP7 inhibitor. Here, we show that PRN1126, developed as an exclusively LMP7
      specific inhibitor, has limited effects on IL-6 secretion, experimental colitis,
      and experimental autoimmune encephalomyelitis (EAE). We demonstrate that
      prolonged exposure of cells with ONX 0914 leads to inhibition of both LMP7 and
      LMP2. Co-inhibition of LMP7 and LMP2 with PRN1126 and LMP2 inhibitors LU-001i or
      ML604440 impairs MHC class I cell surface expression, IL-6 secretion, and
      differentiation of naive T helper cells to T helper 17 cells, and strongly
      ameliorates disease in experimental colitis and EAE. Hence, co-inhibition of LMP2
      and LMP7 appears to be synergistic and advantageous for the treatment of
      autoimmune diseases.

PMID- 30279281
TI  - Cyclosporine Biosynthesis in Tolypocladium inflatum Benefits Fungal Adaptation to
      the Environment.
AB  - The cycloundecapeptide cyclosporin A (CsA) was first isolated from the insect
      pathogenic fungus Tolypocladium inflatum for its antifungal activity and later
      developed as an immunosuppressant drug. However, the full biosynthetic mechanism
      of CsA remains unknown and has puzzled researchers for decades. In this study,
      the biosynthetic gene cluster is suggested to include 12 genes encoding enzymes,
      including the nonribosomal peptide synthetase (NRPS) (SimA) responsible for
      assembling the 11 amino acid substrates of cyclosporine and a polyketide synthase
      (PKS) (SimG) to mediate the production of the unusual amino acid (4R)-4-[(E)-2
      butenyl]-4-methyl-l-threonine (Bmt). Individual deletion of 10 genes, isolation
      of intermediates, and substrate feeding experiments show that Bmt is
      biosynthesized by three enzymes, including SimG, SimI, and SimJ. The substrate d
      alanine is catalyzed from l-alanine by alanine racemase SimB. Gene cluster
      transcription is regulated by a putative basic leucine zipper (bZIP)-type protein
      encoded by the cluster gene SimL We also found that the cluster cyclophilin
      (SimC) and transporter (SimD) genes contribute to the tolerance of CsA in the CsA
      producing fungus. We also found that cyclosporine production could enable the
      fungus to outcompete other fungi during cocultivation tests. Deletion of the CsA
      biosynthetic genes also impaired fungal virulence against insect hosts. Taking
      all the data together, in addition to proposing a biosynthetic pathway of
      cyclosporines, the results of this study suggest that CsA produced by this fungus
      might play important ecological roles in fungal environment
      interactions.IMPORTANCE The cyclopeptide cyclosporin A was first isolated from
      the filamentous fungus Tolypocladium inflatum showing antifungal activity and was
      later developed as an immunosuppressant drug. We report the biosynthetic
      mechanism of cyclosporines that are mediated by a cluster of genes encoding NRPS
      and PKS controlled by a bZIP-type transcriptional regulator. The two unusual
      amino acids Bmt and d-Ala are produced by the PKS pathway and alanine racemase,
      respectively. The cyclophilin and transporter genes jointly contribute to fungal
      self-protection against cyclosporines. Cyclosporine confers on T. inflatum the
      abilities to outcompete other fungi in competitive interactions and to facilitate
      fungal infection of insect hosts, which therefore benefits fungal adaptations to
      different environments.

PMID- 30279280
TI  - SsaV Interacts with SsaL to Control the Translocon-to-Effector Switch in the
      Salmonella SPI-2 Type Three Secretion System.
AB  - Nonflagellar type III secretion systems (nf T3SSs) form a cell surface needle
      like structure and an associated translocon that deliver bacterial effector
      proteins into eukaryotic host cells. This involves a tightly regulated hierarchy
      of protein secretion. A switch involving SctP and SctU stops secretion of the
      needle protein. The gatekeeper protein SctW is required for secretion of
      translocon proteins and controls a second switch to start effector secretion.
      Salmonella enterica serovar Typhimurium encodes two T3SSs in Salmonella
      pathogenicity island 1 (SPI-1) and SPI-2. The acidic vacuole containing
      intracellular bacteria stimulates assembly of the SPI-2 T3SS and its translocon.
      Sensing the nearly neutral host cytosolic pH is required for effector
      translocation. Here, we investigated the involvement of SPI-2-encoded proteins
      SsaP (SctP), SsaU (SctU), SsaV (SctV), and SsaL (SctW) in regulation of
      secretion. We found that SsaP and SsaU are involved in the first but not the
      second secretion switch. A random-mutagenesis screen identified amino acids of
      SsaV that regulate translocon and effector secretion. Single substitutions in
      subdomain 4 of SsaV or InvA (SPI-1-encoded SctV) phenocopied mutations of their
      corresponding gatekeepers with respect to translocon and effector protein
      secretion and host cell interactions. SsaL interacted with SsaV in bacteria
      exposed to low ambient pH but not after the pH was raised to 7.2. We propose that
      SsaP and SsaU enable the apparatus to become competent for a secretion switch and
      facilitate the SsaL-SsaV interaction. This mediates secretion of translocon
      proteins until neutral pH is sensed, which causes their dissociation, resulting
      in arrest of translocon secretion and derepression of effector
      translocation.IMPORTANCE Salmonella Typhimurium is an intracellular pathogen that
      uses the SPI-2 type III secretion system to deliver virulence proteins across the
      vacuole membrane surrounding intracellular bacteria. This involves a tightly
      regulated hierarchy of protein secretion controlled by two molecular switches. We
      found that SPI-2-encoded proteins SsaP and SsaU are involved in the first but not
      the second secretion switch. We identify key amino acids of the inner membrane
      protein SsaV that are required to interact with the so-called gatekeeper protein
      SsaL and show that the dissociation of SsaV-SsaL causes the second switch,
      leading to delivery of effector proteins. Our results provide insights into the
      molecular events controlling virulence-associated type III secretion and suggest
      a broader model describing how the process is regulated.

PMID- 30279284
TI  - Ethanolamine Influences Human Commensal Escherichia coli Growth, Gene Expression,
      and Competition with Enterohemorrhagic E. coli O157:H7.
AB  - A core principle of bacterial pathogenesis is that pathogens preferentially
      utilize metabolites that commensal bacteria do not in order to sidestep
      nutritional competition. The metabolite ethanolamine (EA) is well recognized to
      play a central role in host adaptation for diverse pathogens. EA promotes growth
      and influences virulence during host infection. Although genes encoding EA
      utilization have been identified in diverse bacteria (nonpathogenic and
      pathogenic), a prevailing idea is that commensal bacteria do not utilize EA to
      enhance growth, and thus, EA is a noncompetitive metabolite for pathogens. Here,
      we show that EA augments growth of two human commensal strains of Escherichia
      coli Significantly, these commensal strains grow more rapidly than, and even
      outcompete, the pathogen enterohemorrhagic E. coli O157:H7 specifically when EA
      is provided as the sole nitrogen source. Moreover, EA-dependent signaling is
      similarly conserved in the human commensal E. coli strain HS and influences
      expression of adhesins. These findings suggest a more extensive role for EA
      utilization in bacterial physiology and host-microbiota-pathogen interactions
      than previously appreciated.IMPORTANCE The microbiota protects the host from
      invading pathogens by limiting access to nutrients. In turn, bacterial pathogens
      selectively exploit metabolites not readily used by the microbiota to establish
      infection. Ethanolamine has been linked to pathogenesis of diverse pathogens by
      serving as a noncompetitive metabolite that enhances pathogen growth as well as a
      signal that modulates virulence. Although ethanolamine is abundant in the
      gastrointestinal tract, the prevailing idea is that commensal bacteria do not
      utilize EA, and thus, EA utilization has been particularly associated with
      pathogenesis. Here, we provide evidence that two human commensal Escherichia coli
      isolates readily utilize ethanolamine to enhance growth, modulate gene
      expression, and outgrow the pathogen enterohemorrhagic E. coli These data
      indicate a more complex role for ethanolamine in host-microbiota-pathogen
      interactions.

PMID- 30279283
TI  - An Introduced Crop Plant Is Driving Diversification of the Virulent Bacterial
      Pathogen Erwinia tracheiphila.
AB  - Erwinia tracheiphila is the causal agent of bacterial wilt of cucurbits, an
      economically important phytopathogen affecting an economically important
      phytopathogen affecting few cultivated Cucurbitaceae few cultivated Cucurbitaceae
      host plant species in temperate eastern North America. However, essentially
      nothing is known about E. tracheiphila population structure or genetic diversity.
      To address this shortcoming, a representative collection of 88 E. tracheiphila
      isolates was gathered from throughout its geographic range, and their genomes
      were sequenced. Phylogenomic analysis revealed three genetic clusters with
      distinct hrpT3SS virulence gene repertoires, host plant association patterns, and
      geographic distributions. Low genetic heterogeneity within each cluster suggests
      a recent population bottleneck followed by population expansion. We showed that
      in the field and greenhouse, cucumber (Cucumis sativus), which was introduced to
      North America by early Spanish conquistadors, is the most susceptible host plant
      species and the only species susceptible to isolates from all three lineages. The
      establishment of large agricultural populations of highly susceptible C. sativus
      in temperate eastern North America may have facilitated the original emergence of
      E. tracheiphila into cucurbit agroecosystems, and this introduced plant species
      may now be acting as a highly susceptible reservoir host. Our findings have broad
      implications for agricultural sustainability by drawing attention to how
      worldwide crop plant movement, agricultural intensification, and locally unique
      environments may affect the emergence, evolution, and epidemic persistence of
      virulent microbial pathogens.IMPORTANCE Erwinia tracheiphila is a virulent
      phytopathogen that infects two genera of cucurbit crop plants, Cucurbita spp.
      (pumpkin and squash) and Cucumis spp. (muskmelon and cucumber). One of the
      unusual ecological traits of this pathogen is that it is limited to temperate
      eastern North America. Here, we complete the first large-scale sequencing of an
      E. tracheiphila isolate collection. From phylogenomic, comparative genomic, and
      empirical analyses, we find that introduced Cucumis spp. crop plants are driving
      the diversification of E. tracheiphila into multiple lineages. Together, the
      results from this study show that locally unique biotic (plant population) and
      abiotic (climate) conditions can drive the evolutionary trajectories of locally
      endemic pathogens in unexpected ways.

PMID- 30279282
TI  - Dual Role of a Viral Polymerase in Viral Genome Replication and Particle Self
      Assembly.
AB  - Double-stranded RNA (dsRNA) viruses package several RNA-dependent RNA polymerases
      (RdRp) together with their dsRNA genome into an icosahedral protein capsid known
      as the polymerase complex. This structure is highly conserved among dsRNA viruses
      but is not found in any other virus group. RdRp subunits typically interact
      directly with the main capsid proteins, close to the 5-fold symmetric axes, and
      perform viral genome replication and transcription within the icosahedral protein
      shell. In this study, we utilized Pseudomonas phage Phi6, a well-established
      virus self-assembly model, to probe the potential roles of the RdRp in dsRNA
      virus assembly. We demonstrated that Phi6 RdRp accelerates the polymerase complex
      self-assembly process and contributes to its conformational stability and
      integrity. We highlight the role of specific amino acid residues on the surface
      of the RdRp in its incorporation during the self-assembly reaction. Substitutions
      of these residues reduce RdRp incorporation into the polymerase complex during
      the self-assembly reaction. Furthermore, we determined that the overall
      transcription efficiency of the Phi6 polymerase complex increased when the number
      of RdRp subunits exceeded the number of genome segments. These results suggest a
      mechanism for RdRp recruitment in the polymerase complex and highlight its novel
      role in virion assembly, in addition to the canonical RNA transcription and
      replication functions.IMPORTANCE Double-stranded RNA viruses infect a wide
      spectrum of hosts, including animals, plants, fungi, and bacteria. Yet genome
      replication mechanisms of these viruses are conserved. During the infection
      cycle, a proteinaceous capsid, the polymerase complex, is formed. An essential
      component of this capsid is the viral RNA polymerase that replicates and
      transcribes the enclosed viral genome. The polymerase complex structure is well
      characterized for many double-stranded RNA viruses. However, much less is known
      about the hierarchical molecular interactions that take place in building up such
      complexes. Using the bacteriophage Phi6 self-assembly system, we obtained novel
      insights into the processes that mediate polymerase subunit incorporation into
      the polymerase complex for generation of functional structures. The results
      presented pave the way for the exploitation and engineering of viral self
      assembly processes for biomedical and synthetic biology applications. An
      understanding of viral assembly processes at the molecular level may also
      facilitate the development of antivirals that target viral capsid assembly.

PMID- 30279285
TI  - A Member of the Ferlin Calcium Sensor Family Is Essential for Toxoplasma gondii
      Rhoptry Secretion.
AB  - Invasion of host cells by apicomplexan parasites such as Toxoplasma gondii is
      critical for their infectivity and pathogenesis. In Toxoplasma, secretion of
      essential egress, motility, and invasion-related proteins from microneme
      organelles is regulated by oscillations of intracellular Ca2+ Later stages of
      invasion are considered Ca2+ independent, including the secretion of proteins
      required for host cell entry and remodeling from the parasite's rhoptries. We
      identified a family of three Toxoplasma proteins with homology to the ferlin
      family of double C2 domain-containing Ca2+ sensors. In humans and model
      organisms, such Ca2+ sensors orchestrate Ca2+-dependent exocytic membrane fusion
      with the plasma membrane. Here we focus on one ferlin that is conserved across
      the Apicomplexa, T. gondii FER2 (TgFER2). Unexpectedly, conditionally TgFER2
      depleted parasites secreted their micronemes normally and were completely motile.
      However, these parasites were unable to invade host cells and were therefore not
      viable. Knockdown of TgFER2 prevented rhoptry secretion, and these parasites
      failed to form the moving junction at the parasite-host interface necessary for
      host cell invasion. Collectively, these data demonstrate the requirement of
      TgFER2 for rhoptry secretion in Toxoplasma tachyzoites and suggest a possible
      Ca2+ dependence of rhoptry secretion. These findings provide the first
      mechanistic insights into this critical yet poorly understood aspect of
      apicomplexan host cell invasion.IMPORTANCE Apicomplexan protozoan parasites, such
      as those causing malaria and toxoplasmosis, must invade the cells of their hosts
      in order to establish a pathogenic infection. Timely release of proteins from a
      series of apical organelles is required for invasion. Neither the vesicular
      fusion events that underlie secretion nor the observed reliance of the various
      processes on changes in intracellular calcium concentrations is completely
      understood. We identified a group of three proteins with strong homology to the
      calcium-sensing ferlin family, which are known to be involved in protein
      secretion in other organisms. Surprisingly, decreasing the amounts of one of
      these proteins (TgFER2) did not have any effect on the typically calcium
      dependent steps in invasion. Instead, TgFER2 was essential for the release of
      proteins from organelles called rhoptries. These data provide a tantalizing first
      look at the mechanisms controlling the very poorly understood process of rhoptry
      secretion, which is essential for the parasite's infection cycle.

PMID- 30279287
TI  - Erratum for Abisado et al., "Bacterial Quorum Sensing and Microbial Community
      Interactions".

PMID- 30279288
TI  - Contradictory Results in Microbiome Science Exemplified by Recent Drosophila
      Research.
AB  - The bacterium Lactobacillus plantarum is prevalent in animal guts and is widely
      regarded as beneficial and probiotic. D. Fast et al. (mBio 9:e01114-18, 2018,
      https://doi.org/10.1128/mBio.01114-18) make the surprising discovery that L.
      plantarum reduces the life span of Drosophila melanogaster and link this effect
      with the loss and weakened proliferation of stem cells in the Drosophila gut.
      These results are apparently at odds with published evidence for beneficial
      effects of L. plantarum, especially promoting high developmental rates and
      stimulating stem cell proliferation in young Drosophila The among-study
      discrepancies highlight the context dependence of many effects of gut microbes on
      host health, likely influenced by host age and genotype, variation among
      bacterial strains, and diet. The diversity of results offers an opportunity to
      elucidate a fundamental mechanism(s) and the circumstances that dictate whether
      gut bacteria have positive or negative effects on host health. These studies also
      reinforce the value of Drosophila as an emerging model system for probiotic
      science.

PMID- 30279289
TI  - Erratum for Penewit et al., "Efficient and Scalable Precision Genome Editing in
      Staphylococcus aureus through Conditional Recombineering and CRISPR/Cas9-Mediated
      Counterselection".

PMID- 30279286
TI  - Proteome Analysis Reveals the Conidial Surface Protein CcpA Essential for
      Virulence of the Pathogenic Fungus Aspergillus fumigatus.
AB  - Aspergillus fumigatus is a common airborne fungal pathogen of humans and a
      significant source of mortality in immunocompromised individuals. Here, we
      provide the most extensive cell wall proteome profiling to date of A. fumigatus
      resting conidia, the fungal morphotype pertinent to first contact with the host.
      Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified
      proteins within the conidial cell wall by hydrogen-fluoride (HF)-pyridine
      extraction and proteins exposed on the surface using a trypsin-shaving approach.
      One protein, designated conidial cell wall protein A (CcpA), was identified by
      both methods and was found to be nearly as abundant as hydrophobic rodlet layer
      forming protein RodA. CcpA, an amphiphilic protein, like RodA, peaks in
      expression during sporulation on resting conidia. Despite high cell wall
      abundance, the cell surface structure of DeltaccpA resting conidia appeared
      normal. However, trypsin shaving of DeltaccpA conidia revealed novel surface
      exposed proteins not detected on conidia of the wild-type strain. Interestingly,
      the presence of swollen DeltaccpA conidia led to higher activation of neutrophils
      and dendritic cells than was seen with wild-type conidia and caused significantly
      less damage to epithelial cells in vitro In addition, virulence was highly
      attenuated when cortisone-treated, immunosuppressed mice were infected with
      DeltaccpA conidia. CcpA-specific memory T cell responses were detectable in
      healthy human donors naturally exposed to A. fumigatus conidia, suggesting a role
      for CcpA as a structural protein impacting conidial immunogenicity rather than
      possessing a protein-intrinsic immunosuppressive effect. Together, these data
      suggest that CcpA serves as a conidial stealth protein by altering the conidial
      surface structure to minimize innate immune recognition.IMPORTANCE The mammalian
      immune system relies on recognition of pathogen surface antigens for targeting
      and clearance. In the absence of immune evasion strategies, pathogen clearance is
      rapid. In the case of Aspergillus fumigatus, the successful fungus must avoid
      phagocytosis in the lung to establish invasive infection. In healthy individuals,
      fungal spores are cleared by immune cells; however, in immunocompromised
      patients, clearance mechanisms are impaired. Here, using proteome analyses, we
      identified CcpA as an important fungal spore protein involved in pathogenesis. A.
      fumigatus lacking CcpA was more susceptible to immune recognition and prompt
      eradication and, consequently, exhibited drastically attenuated virulence. In
      infection studies, CcpA was required for virulence in infected immunocompromised
      mice, suggesting that it could be used as a possible immunotherapeutic or
      diagnostic target in the future. In summary, our report adds a protein to the
      list of those known to be critical to the complex fungal spore surface
      environment and, more importantly, identifies a protein important for conidial
      immunogenicity during infection.

PMID- 30279290
TI  - Erratum for Franco et al., "A Novel Secreted Protein, MYR1, Is Central to
      Toxoplasma's Manipulation of Host Cells".

PMID- 30279291
TI  - First person - Lotte de Winde.
AB  - First Person is a series of interviews with the first authors of a selection of
      papers published in Journal of Cell Science, helping early-career researchers
      promote themselves alongside their papers. Lotte de Winde is the first author on
      'C-type lectin-like receptor 2 (CLEC-2)-dependent dendritic cell migration is
      controlled by tetraspanin CD37', published in Journal of Cell Science. Lotte
      conducted the research in this article while a PhD student at the Radboud
      Institute for Molecular Life Sciences, The Netherlands, under the supervision of
      Prof. Annemiek van Spriel and Prof. Carl Figdor. She is now a Postdoctoral
      Research Fellow in the lab of Dr Sophie Acton at the MRC Laboratory for Molecular
      Cell Biology, UK. Here, she studies the plasma membrane organisation and dynamics
      of podoplanin and its partner proteins on fibroblastic reticular cells (FRCs),
      and how changes in this organisation shape downstream signalling and FRC
      function.

PMID- 30279292
TI  - Use of the STEMI Team for Treatment of Patients With Pulmonary Embolism: A Pilot
      Study.
AB  - BACKGROUND: Patients with massive and submassive pulmonary embolism (PE) require
      rapid identification, triage, and consideration for reperfusion therapy. Use of
      an existing ST-segment elevation myocardial infarction (STEMI) team and
      activation protocol may be an effective means to care for these patients.
      OBJECTIVE: The objective of this analysis was to evaluate a pilot study using the
      STEMI team and a dedicated PE protocol for treatment of patients with massive and
      submassive PE. METHODS: From June 2014 to April 2016, a total of 40 patients with
      massive and submassive PE were evaluated. Baseline demographics, mode of hospital
      entry (transfer-in, in-hospital, and emergency department [ED] arrival),
      treatment time intervals (door to computed tomography PE protocol [CTPE], CTPE to
      invasive pulmonary angiogram, door to treatment time), procedures performed, and
      in-hospital clinical events were collected. RESULTS: Mean age was 56 +/- 14
      years, 17 (42%) were male, and 12 (30%) had a prior history of deep venous
      thrombosis or PE. Twenty-three patients (57%) had massive PE and 17 patients
      (43%) had submassive PE. Mode of hospital entry was transfer-in (38%), in
      hospital (20%), and ED arrival (42%). Four patients (10%) presented with cardiac
      arrest, 8 patients (20%) required intubation, and 5 patients (12%) required
      extracorporeal membrane oxygenation. Ten patients (25%) received anticoagulation
      therapy or placement of inferior vena cava filter, 3 patients (7.5%) received
      diagnostic pulmonary angiography alone, and 27 patients (67.5%) received
      endovascular treatment. For patients arriving via the ED, door to CTPE was 4.9 +/
      3.6 hours, CTPE to diagnostic pulmonary angiography was 7.8 +/- 8.5 hours, and
      door to treatment time was 10.2 +/- 9.0 hours. Endovascular devices utilized
      included combinations of rheolytic and other thrombectomy devices as well as
      catheter-directed fibrinolysis. Length of hospital stay was 15 +/- 15 days and in
      hospital survival rate was 90%. CONCLUSIONS: Use of an existing STEMI team and
      activation protocol is a feasible method to care for patients with massive and
      submassive PE. This pilot study demonstrated rapid treatment times with low in
      hospital mortality.

PMID- 30279293
TI  - Comparative Effectiveness Study of Drug-Eluting and Bare-Metal Peripheral Artery
      Stents in Endovascular Femoropopliteal Artery Revascularization.
AB  - OBJECTIVES: Paclitaxel drug-eluting stents (DESs) have been shown to improve
      primary patency of femoropopliteal lesions compared to plain balloon angioplasty
      with provisional bare-metal stents (BMSs) in randomized controlled studies.
      However, data are lacking on patency outcomes of real-world DES use relative to
      BMS use. This study compared clinically driven target-lesion revascularization
      (TLR), target-vessel revascularization (TVR), and target-limb revascularization
      outcomes at 1 year between DES and BMS treatments in a real-world setting.
      METHODS: The study identified 174 DES (Zilver PTX; Cook Medical) and 784 BMS
      femoropopliteal interventions from the available 969 Excellence in Peripheral
      Artery Disease (XLPAD) registry patients between October 2013 and December 2016.
      We analyzed both unmatched (174 DES and 784 BMS) and propensity score (PS)
      matched datasets (174 for each). RESULTS: This study found that patients who
      underwent DES femoropopliteal endovascular revascularization had significantly
      lower TLR rates in both unmatched (hazard ratio [HR], 0.57; 95% confidence
      interval [CI], 0.35-0.91; P=.02) and matched data (HR, 0.50 95% CI, 0.27-0.91;
      P=.02). The DES group had a 43% lower TVR risk than the BMS group in the PS
      matched cohort (HR, 0.57; 95% CI, 0.33-0.98; P=.04). Mortality rate in the DES
      group (5%) was significantly higher than the BMS group in both unmatched (2%;
      P=.04) and matched groups (1%; P=.046) at 1 year. CONCLUSIONS: Patients treated
      with DES had higher lesion and vessel patency than BMS after adjusting for
      confounding, which included complexity of lesion characteristics and operators'
      clinical decision-making regarding selection of treatment modalities, in
      femoropopliteal endovascular interventions in a real-world registry.

PMID- 30279294
TI  - Outcome of Patients Undergoing Transcatheter Aortic Valve Implantation After
      Prior Balloon Aortic Valvuloplasty.
AB  - OBJECTIVES: Transcatheter aortic valve implantation (TAVI) is an effective
      treatment for severe aortic stenosis. Yet, balloon aortic valvuloplasty (BAV) is
      still occasionally offered to apparently inoperable patients as bridge or
      destination therapy, with some eventually receiving TAVI. We aimed to determine
      whether prior BAV would unfavorably impact TAVI. METHODS: The RISPEVA dataset was
      analyzed to compare the outcomes of non-BAV subjects undergoing TAVI vs those
      with prior BAV. Outcomes of interest were procedural results, hospital stay, and
      in-hospital outcomes, including major adverse events. Unadjusted and propensity
      matched analyses were performed. RESULTS: A total of 1683 patients were included
      (1541 [91.6%] non-BAV and 142 [8.4%] prior BAV). Device success, procedural
      success, major adverse events and their individual components were all similar in
      the two groups, in both unadjusted and propensity-matched analyses. However, non
      BAV patients had significantly shorter intensive/coronary care unit stay (8.1 +/-
      23.0 days vs 13.4 +/- 35.2 days; P=.03) and total hospital stay (12.4 +/- 22.1
      days vs 17.2 +/- 32.7 days; P=.02). Similar findings were obtained even in the
      propensity-matched groups (6.3 +/- 11.9 days vs 13.6 +/- 35.5 days [P=.05] and
      10.5 +/- 13.8 days vs 17.4 +/- 33.1 days [P=.03], respectively). No significant
      interaction was found between device type and prior BAV status. CONCLUSION: BAV
      continues to offer a palliative solution to patients with unclear or poor
      prognosis and deemed at too high risk for emergent TAVI or surgery. Subjects
      undergoing BAV and surviving the post-BAV period can undergo TAVI without a
      significantly increased risk of in-hospital adverse events in comparison with non
      BAV patients.

PMID- 30279295
TI  - Use of Ultrasound-Accelerated, Catheter-Directed Local Thrombolysis for Venous
      and Arterial Occlusions in a Pediatric Hospital.
AB  - OBJECTIVES: Acute vascular thrombosis is associated with significant morbidity
      and mortality in children. Traditional therapies with angioplasty and manual
      aspiration thrombectomy are described in the pediatric population; however, data
      regarding the use of ultrasound-assisted catheter-directed thrombolysis in a
      pediatric hospital are lacking. METHODS: All patients treated at our center with
      ultrasound-assisted catheter-directed thrombolysis from 2014-2018 were reviewed.
      RESULTS: Ten patients with systemic venous (n = 5), pulmonary artery (n = 4), and
      systemic arterial (n = 1) were treated (20 total vessels), including 2 adults
      post Fontan palliation. The median age was 11.2 years (range, 9 months to 34.2
      years) and median weight was 46.6 kg (range, 6.81-01.6 kg). Therapy was not
      completed in 1 patient. Significant improvement in clot burden/symptomatic
      improvement was seen in 8 patients (no improvement seen in 1 patient with acute
      and chronic thrombosis). There were no major bleeding or neurologic complications
      related to therapy. CONCLUSIONS: The use of ultrasound-assisted catheter-directed
      thrombolysis in a pediatric center is a valuable modality for treating acute
      thrombosis with an acceptable safety profile.

PMID- 30279296
TI  - Identification of Coronary Vasospasm as a Cause of Recurrent Acute Coronary
      Syndrome.
AB  - A case highlighting the importance of nitrate administration, as routinely
      performed during coronary arteriography.

PMID- 30279297
TI  - Thrombotic Occlusion of Ectatic Coronary Arteries in a Young Patient.
AB  - Multiple rounds of aspiration thrombectomy followed by balloon angioplasty of the
      left anterior descending (LAD) failed to completely restore the flow into the
      distal LAD secondary to re-occlusion from thrombus formation.

PMID- 30279298
TI  - Aortic Pseudoaneurysm Causing Compression of the Left Main Coronary Artery.
AB  - A 75-year-old man with a history of mechanical aortic valve replacement with
      aortic conduit for severe aortic insufficiency underwent routine screening
      computed tomography evaluation revealing right coronary anastomosis endoleak and
      proximal aortic root pseudoaneurysm.

PMID- 30279299
TI  - Recannulation of Distal Radial Artery for Staged Procedure After Successful
      Primary Percutaneous Coronary Intervention.
AB  - There are limited data regarding the snuffbox approach. Our experience highlights
      the feasibility of snuffbox approach as the access route for primary PCI and
      recannulation of distal radial artery for staged PCI.

PMID- 30279300
TI  - Layered Neointimal Pattern Secondary to Intraluminal Clot Organization in an
      Optical Coherence Tomography Longitudinal Study.
AB  - We present a patient with non-obstructive intraluminal clot protrusion treated
      with medical therapy. Follow-up OCT scan showed layered neointimal changes
      similar to images observed in stent failure.

PMID- 30279301
TI  - Four-Layer Stent Sandwich for Recurrent In-Stent Occlusion of the Right Coronary
      Artery: "The Four Musketeers" Fighting for Coronary Flow.
AB  - A 70-year-old man with a history of two successfully treated in-stent chronic
      total occlusions of the ostial right coronary artery using drug-eluting stents
      presented with typical angina.

PMID- 30279302
TI  - Compartment Syndrome: A Rare and Frightening Complication of Transradial
      Catheterization.
AB  - The compartment syndrome is a severe complication of transradial approach and can
      be prevented by prompt treatment of forearm hematoma; otherwise, fasciotomies are
      urgent.

PMID- 30279303
TI  - The effect of Tropaeolum majus L. on bacterial infections and in vitro efficacy
      on apoptosis and DNA lesions in hyperosmotic stress.
AB  - Tropaeolum majus L. (T. majus) or nasturtium is a medicinal plant widespread in
      the areas with temperate climate, commonly used in culinary and in traditional
      medicine due to therapeutic properties. In the last few years, various effects of
      the flowers and leaves of this plant have been studied, but their benefits are
      not fully known. The aim of the study was to identify the phenolic compounds from
      T. majus edible flowers in relation with its antioxidant capacity and the
      antimicrobial activity against different bacteria and Candida albicans. In
      addition, the impact of natural extract on oxidative stress, inflammation and
      apoptosis was analysed on human umbilical vein endothelial cells (HUVECs) exposed
      to normotonic and hypertonic conditions. The major phenolic acids, identified by
      HPLC-RP with UV detection, were gallic acid, caffeic acid and p-coumaric and
      predominant flavonoids were quercetin, epicatechin and luteolin. The both
      fractions of T. majus were rich sources of polyphenols with marked antioxidant
      activity, evidenced by TEAC or DPPH methods. The extract exhibited a week
      antibacterial effect on some strains of streptococcus, without antifungal or
      antibacterial effect on gram negative bacteria. T. majus extract increased the
      p53 and Bcl-2 expressions and diminished the DNA lesions indicating the
      protective and antiapoptotic effects in vitro, on endothelial cells exposed to
      hyperosmotic stress. These experimental findings suggest that T. majus can exert
      some protection against bacterial infections and reduce apoptosis and DNA lesions
      in hypertonic conditions.

PMID- 30279304
TI  - Recent advances in the role of AMP-activated protein kinase in metabolic
      reprogramming of metastatic cancer cells: targeting cellular bioenergetics and
      biosynthetic pathways for anti-tumor treatment.
AB  - Growing data indicate that tumor progression and metastasis is dependent on the
      reprograming of cellular metabolism. Rapidly growing cancer cells undergo
      metabolic stress in a harsh microenvironment. AMP-activated protein kinase (AMPK)
      is an energy sensing factor that regulates bioenergetics and biosynthetic
      pathways within the cell, but its role under metastasis is in dispute. The best
      studied phenotype of cancer cells is aerobic glycolysis (the Warburg effect), an
      increased catabolism of glucose to lactate. However, glycolysis and mitochondrial
      oxidative phosphorylation may operate simultaneously in cancer cells. Many tumors
      may switch between these pathways accordingly to the current requirements. The
      alterations in metabolism of cancer cells combined with the overexpression of
      oncogenes (c-Myc) and transcription factors (Hypoxia-inducible factor 1a) confer
      a great advantage to malignant cells to avoid reactive oxygen species induced
      apoptosis. The determination of the role of AMPK network in metabolic
      reprogramming of metastatic cancer cells may help to identify the selective
      molecular targets for efficient anti-cancer therapies. In this review, we discuss
      the implications of AMPK activation in metabolic reprogramming of cancer cells
      and we present several potential therapeutic strategies targeting cancer cell
      metabolism. AMPK activator, biguanide metformin, either alone or in combination
      with other drugs, may selectively modulate signaling pathways, expresses the
      chemopreventive potential and can be used in current anti-cancer approaches.
      However, the ambiguous data suggest that the activation of AMPK may induce
      multiple effects and thus potential therapeutic anti-cancer approach should be
      carefully considered in relation to metabolic network of cancer cell signaling
      and other determinants such tumor stage and origin as well.

PMID- 30279305
TI  - Hydrogen sulfide modulates gastric acid secretion in rats via involvement of
      substance P and nuclear factor-kappaB signaling.
AB  - Hydrogen sulfide (H2S) promotes gastric acid secretion in rats. The present study
      aimed to test the hypothesis that H2S regulates this response via activating
      TRPV1 channel and through activation of the nuclear factor-kappaB (NF-kappaB)
      pathway. Male Wistar rats were randomly divided into the sodium hydrosulfide
      (NaHS, 100 MUmol/kg b.w.) group, pyrrolidine dithiocarbamate (PDTC, 100 MUmol/kg
      b.w.) group, PDTC (100 MUmol/kg b.w.) + NaHS (100 MUmol /kg b.w.) group,
      capsazepine (0.1 mM) + NaHS (100 MUmol /kg b.w.) group and L703606 (0.1 mM) +
      NaHS (100 MUmol /kg b.w.) group. The acidity of gastric juice before injection
      and after injection were determined by a pH meter. The results showed that sodium
      hydrosulfide (NaHS), an exogenous H2S donor, significantly reduced the pH of
      gastric juice when injected into the enterocoelia. Further, the promotional
      effect of NaHS on gastric acid secretion could be attenuated by capsazepine, a
      transient receptor potential vanilloid 1 (TRPV1) antagonist; L703606, a
      neurokinin 1 (NK1) receptor antagonist; and PDTC, a NF-kappaB inhibitor. The data
      from these experiments suggest that NaHS exerts an excitatory effect on gastric
      acid secretion possibly mediated by TRPV1 channel activation in sensory nerve
      terminals with the consequent release of substance P and in a NF-kappaB 
      dependent manner.

PMID- 30279306
TI  - Sleep disturbance and disease activity in adult patients with inflammatory bowel
      diseases.
AB  - The aim of the study was to identify whether poor quality of sleep is connected
      to inflammatory bowel disease (IBD) and if so, whether sleep disturbances are
      related to disease activity. Prospective, observational cohort study was
      performed. In all enrolled adult patients, the disease activity was assessed by
      using Crohn's Disease Activity Index (CDAI) for Crohn's disease (CD) and Partial
      Mayo Score for ulcerative colitis (UC), respectively. All patients were also
      asked to respond to a questionnaire to define Pittsburgh Quality Sleep Index
      (PSQI). Sixty-five patients were enrolled in our study: n = 30 with CD and n = 35
      with UC. The poor sleep was noted in 78% (40/51) patients with clinically
      exacerbation and in 35% (5/14) patients in remission (P = 0.002; OR 6.5, 95%
      confidence interval, 1.8 - 23.6). A global PSQI score of 5 points yielded a
      sensitivity of 84%, a specificity of 39%, and a positive predictive value of 89%
      for discriminating participants with exacerbation of IBD from those in clinical
      remission; PSQI higher than 6 indicates the exacerbation of IBD with 77%
      sensitivity and 62% specificity. The poorest sleep quality was reported in IBD
      patients with severe exacerbations (9.1 +/- 2.9). Sleep disturbance was confirmed
      in adult IBD patients, both in CD and UC. Confirmation of the relationship
      between sleep abnormalities and IBD may show the new pathway in pathophysiology,
      course and treatment of IBD.

PMID- 30279307
TI  - Vasodilating, spasmolytic, inotropic and chronotropic activities of curcuminoids
      from Curcuma longa in isolated organ preparations of guinea pigs.
AB  - Turmeric is a yellowish orange spice, widely used in Asian cuisine and obtained
      from the rhizome of Curcuma longa. It is a mixture of three curcuminoids namely,
      curcumin, demethoxycurcumin and bisdemethoxycurcumin. Turmeric has been used as a
      medicinal substance since ancient times for respiratory and gastrointestinal
      problems. The aim of the present study was to investigate which curcuminoid
      contributes to the observed pharmacological activities, all three curcuminoids,
      the major curcumin metabolite tetrahydrocurcumin, and the non-enzymatic curcumin
      hydrolysis products ferulic acid, feruloyl methane and vanillin were analyzed for
      spasmolytic, inotropic and chronotropic activity. Furthermore, their uptake in
      respective tissue samples was also investigated and correlated with activity.
      Spasmolytic activity was determined in guinea pig ileum, aorta and pulmonary
      artery. Inotropic and chronotropic activity was determined on guinea pig
      papillary muscles and right atrium respectively, while tissue uptake was
      quantified by using high-performance liquid chromatography (HPLC). All the
      curcuminoids exhibited significant spasmolytic activity with highest EC50 values
      for bisdemethoxycurcumin (5.8 +/- 0.6 MUM) followed by curcumin (12.9 +/- 0.7
      MUM), demethoxycurcumin (16.8 +/- 3 MUM) and tetrahydrocurcumin (22.9 +/- 1.5
      MUM). While only demethoxycurcumin was able to significantly relax the pulmonary
      artery with EC50 value of 15.78 +/- 0.85 MUM. All three curcuminoids showed mild
      negative chronotropic effects in the isolated right atrium; tetrahydrocurcumin
      demonstrated no activity. Curcumin and bisdemethoxycurcumin also showed mild
      positive inotropic effect whereas demethoxycurcumin and tetrahydrocurcumin
      exhibited weak negative inotropic one. Interestingly, ferulic acid, feruloyl
      methane and vanillin demonstrated no pharmacologicical activity at all in the
      various isolated organs. All three curcuminoids and tetrahydrocurcumin showed
      high uptake into the various tissues where concentrations correlated with
      pharmacological activity. The results indicate pronounced differences in the in
      vitro pharmacological activities of curcumin, demethoxycurcumin,
      bisdemethoxycurcumin and tetrahydrocurcumin which have to be considered in humans
      after per-oral intake of turmeric powder.

PMID- 30279309
TI  - Compact convolutional neural networks for classification of asynchronous steady
      state visual evoked potentials.
AB  - OBJECTIVE: Steady-state visual evoked potentials (SSVEPs) are neural oscillations
      from the parietal and occipital regions of the brain that are evoked from
      flickering visual stimuli. SSVEPs are robust signals measurable in the
      electroencephalogram (EEG) and are commonly used in brain-computer interfaces
      (BCIs). However, methods for high-accuracy decoding of SSVEPs usually require
      hand-crafted approaches that leverage domain-specific knowledge of the stimulus
      signals, such as specific temporal frequencies in the visual stimuli and their
      relative spatial arrangement. When this knowledge is unavailable, such as when
      SSVEP signals are acquired asynchronously, such approaches tend to fail.
      APPROACH: In this paper, we show how a compact convolutional neural network
      (Compact-CNN), which only requires raw EEG signals for automatic feature
      extraction, can be used to decode signals from a 12-class SSVEP dataset without
      the need for user-specific calibration. MAIN RESULTS: The Compact-CNN
      demonstrates across subject mean accuracy of approximately 80%, out-performing
      current state-of-the-art, hand-crafted approaches using canonical correlation
      analysis (CCA) and Combined-CCA. Furthermore, the Compact-CNN approach can reveal
      the underlying feature representation, revealing that the deep learner extracts
      additional phase- and amplitude-related features associated with the structure of
      the dataset. SIGNIFICANCE: We discuss how our Compact-CNN shows promise for BCI
      applications that allow users to freely gaze/attend to any stimulus at any time
      (e.g. asynchronous BCI) as well as provides a method for analyzing SSVEP signals
      in a way that might augment our understanding about the basic processing in the
      visual cortex.

PMID- 30279308
TI  - An endogeous defensive concept, renewed cytoprotection/adaptive cytoprotection:
      intra(per)-oral/intraastric strong alcohol in rat. Involvement of
      pentadecapeptide BPC 157 and nitric oxide system.
AB  - With intra(per)-oral strong alcohol application at the tongue, swallowed, we
      renewed Robert's stomach cytoprotection/adaptive cytoprotection concept. We
      assessed strong (96%) alcohol-induced severe or minute lesions in stomach, tongue
      esophagus-stomach-duodenum lesions, and sphincter pressure (lower esophageal and
      pyloric) upon administration intragastrically (at 1 h) or intra(per)-orally at
      the tongue, and swallowed (at 1, 5, 15, 30 min; and 1, 2, 24 h). The assessment
      also included combined administrations (intra(per)-oral at the tongue, swallowed
      and intragastric (at 1 h)). Immediate post-alcohol intraperitoneal medication
      (mg/kg) was the stable gastric pentadecapeptide BPC 157 (0.01, 0.00001; a
      Robert's cytoprotection mediator; with a therapeutic effect), NOS-blocker L-NAME
      (5), and NOS-substrate L-arginine (100 mg), (NO-system involvement). After
      intragastric strong alcohol administration, severe stomach ulcerations appeared
      along with widespread tongue, esophagus, duodenum redness, and minimal sphincter
      pressures. By contrast, a particular syndrome (immediate overlapping of
      cytoprotection/adaptive cytoprotection) (minute gastric lesion or largely
      attenuated hemorrhagic ulceration, tongue affected, minute esophageal and
      duodenal lesions, but with intact mucosa; sphincters pressures lowered) appeared
      after intra(per)-oral administration (1 min-24 h) as well as after combined
      administrations (intra(per)-oral + intragastric). BPC 157 apparently cured all
      alcohol-lesions, amplified the spontaneously initiated strong mucosal beneficial
      effect, rescued sphincter pressures; NO-agents (L-arginine (slight mucosal
      amelioration) and L-NAME (aggravation)) showed NO-system involvement, but no
      comparable effects on dropped sphincters pressures. In conclusion, minute gastric
      lesions (with oral application of strong alcohol at the tongue and swallowed,
      without, or with intragastric application of strong alcohol) renew and revise
      Robert's stomach cytoprotection/adaptive cytoprotection concept. The tongue
      becomes a new initial target, resulting in spontaneous reversal of strong alcohol
      stomach lesions. BPC 157 therapy functions also within the redirected complexity
      of Robert's stomach cytoprotection/adaptive cytoprotection concept.

PMID- 30279310
TI  - Cryo-neutron crystallographic data collection and preliminary refinement of left
      handed Z-DNA d(CGCGCG).
AB  - Crystals of left-handed Z-DNA [d(CGCGCG)]2 diffract X-rays to beyond 1 A
      resolution, feature a small unit cell (~18 * 31 * 44 A) and are well hydrated,
      with around 90 water molecules surrounding the duplex in the asymmetric unit. The
      duplex shows regular hydration patterns in the narrow minor groove, on the convex
      surface and around sugar-phosphate backbones. Therefore, Z-DNA offers an ideal
      case to test the benefits of low-temperature neutron diffraction data collection
      to potentially determine the donor-acceptor patterns of first- and second-shell
      water molecules. Nucleic acid fragments pose challenges for neutron
      crystallography because water molecules are located on the surface rather than
      inside sequestered spaces such as protein active sites or channels. Water
      molecules can be expected to display dynamic behavior, particularly in cases
      where water is not part of an inner shell and directly coordinated to DNA atoms.
      Thus, nuclear density maps based on room-temperature diffraction data with a
      resolution of 1.6 A did not allow an unequivocal determination of the
      orientations of water molecules. Here, cryo-neutron diffraction data collection
      for a Z-DNA crystal on the Macromolecular Neutron Diffractometer at the
      Spallation Neutron Source at Oak Ridge National Laboratory and the outcome of an
      initial refinement of the structure are reported. A total of 12 diffraction
      images were recorded with an exposure time of 3.5 h per image, whereby the
      crystal was static for each diffraction image with a 10 degrees  phi rotation
      between images. Initial refinements using these neutron data indicated the
      positions and orientations of 30 water molecules within the first hydration shell
      of the DNA molecule. This experiment constitutes a state-of-the-art approach and
      is the first attempt to our knowledge to determine the low-temperature neutron
      structure of a DNA crystal.

PMID- 30279312
TI  - Structure of glyoxysomal malate dehydrogenase (MDH3) from Saccharomyces
      cerevisiae.
AB  - Malate dehydrogenase (MDH), a carbohydrate and energy metabolism enzyme in
      eukaryotes, catalyzes the interconversion of malate to oxaloacetate (OAA) in
      conjunction with that of nicotinamide adenine dinucleotide (NAD+) to NADH. Three
      isozymes of MDH have been reported in Saccharomyces cerevisiae: MDH1, MDH2 and
      MDH3. MDH1 is a mitochondrial enzyme and a member of the tricarboxylic acid
      cycle, whereas MDH2 is a cytosolic enzyme that functions in the glyoxylate cycle.
      MDH3 is a glyoxysomal enzyme that is involved in the reoxidation of NADH, which
      is produced during fatty-acid beta-oxidation. The affinity of MDH3 for OAA is
      lower than those of MDH1 and MDH2. Here, the crystal structures of yeast apo
      MDH3, the MDH3-NAD+ complex and the MDH3-NAD+-OAA ternary complex were
      determined. The structure of the ternary complex suggests that the active-site
      loop is in the open conformation, differing from the closed conformations in
      mitochondrial and cytosolic malate dehydrogenases.

PMID- 30279311
TI  - Conformational changes on substrate binding revealed by structures of
      Methylobacterium extorquens malate dehydrogenase.
AB  - Three high-resolution X-ray crystal structures of malate dehydrogenase (MDH; EC
      1.1.1.37) from the methylotroph Methylobacterium extorquens AM1 are presented. By
      comparing the structures of apo MDH, a binary complex of MDH and NAD+, and a
      ternary complex of MDH and oxaloacetate with ADP-ribose occupying the pyridine
      nucleotide-binding site, conformational changes associated with the formation of
      the catalytic complex were characterized. While the substrate-binding site is
      accessible in the enzyme resting state or NAD+-bound forms, the substrate-bound
      form exhibits a closed conformation. This conformational change involves the
      transition of an alpha-helix to a 310-helix, which causes the adjacent loop to
      close the active site following coenzyme and substrate binding. In the ternary
      complex, His284 forms a hydrogen bond to the C2 carbonyl of oxaloacetate, placing
      it in a position to donate a proton in the formation of (2S)-malate.

PMID- 30279313
TI  - Crystal structure of Arabidopsis thaliana peroxiredoxin A C119S mutant.
AB  - Peroxiredoxins (Prxs), a large family of antioxidant enzymes, are abundant in all
      living organisms. Peroxiredoxin A (PrxA) from Arabidopsis thaliana belongs to the
      typical 2-Cys Prx family and is localized in the chloroplast. This article
      reports the crystal structure of a PrxA C119S mutant refined to 2.6 A resolution.
      The protein exists as a decamer both in the crystal structure and in solution.
      The structure is in the reduced state suitable for the approach of peroxide,
      though conformational changes are needed for the resolving process.

PMID- 30279314
TI  - Crystal structure of the ribonuclease-P-protein subunit from Staphylococcus
      aureus.
AB  - Staphylococcus aureus ribonuclease-P-protein subunit (RnpA) is a promising
      antimicrobial target that is a key protein component for two essential cellular
      processes, RNA degradation and transfer-RNA (tRNA) maturation. The first crystal
      structure of RnpA from the pathogenic bacterial species, S. aureus, is reported
      at 2.0 A resolution. The structure presented maintains key similarities with
      previously reported RnpA structures from bacteria and archaea, including the
      highly conserved RNR-box region and aromatic residues in the precursor-tRNA 5'
      leader-binding domain. This structure will be instrumental in the pursuit of
      structure-based designed inhibitors targeting RnpA-mediated RNA processing as a
      novel therapeutic approach for treating S. aureus infections.

PMID- 30279315
TI  - Crystal structure of mutant carboxypeptidase T from Thermoactinomyces vulgaris
      with an implanted S1' subsite from pancreatic carboxypeptidase B.
AB  - A site-directed mutagenesis method has been used to obtain the
      G215S/A251G/T257A/D260G/T262D mutant of carboxypeptidase T from Thermoactinomyces
      vulgaris (CPT), in which the amino-acid residues of the S1' subsite are
      substituted by the corresponding residues from pancreatic carboxypeptidase B
      (CPB). It was shown that the mutant enzyme retained the broad, mainly hydrophobic
      selectivity of wild-type CPT. The mutant containing the implanted CPB S1' subsite
      was crystallized and its three-dimensional structure was determined at 1.29 A
      resolution by X-ray crystallography. A comparison of the three-dimensional
      structures of CPT, the G215S/A251G/T257A/D260G/T262D CPT mutant and CPB showed
      that the S1' subsite of CPT has not been distorted by the mutagenesis and
      adequately reproduces the structure of the CPB S1' subsite. The CPB-like mutant
      differs from CPB in substrate selectivity owing to differences between the two
      enzymes outside the S1' subsite. Moreover, the difference in substrate
      specificity between the enzymes was shown to be affected by residues other than
      those that directly contact the substrate.

PMID- 30279316
TI  - The novel metallo-beta-lactamase PNGM-1 from a deep-sea sediment metagenome:
      crystallization and X-ray crystallographic analysis.
AB  - Metallo-beta-lactamases (MBLs) are present in major Gram-negative pathogens and
      environmental species, and pose great health risks because of their ability to
      hydrolyze the beta-lactam rings of antibiotics such as carbapenems. PNGM-1 was
      the first reported case of a subclass B3 MBL protein that was identified from a
      metagenomic library from deep-sea sediments that predate the antibiotic era. In
      this study, PNGM-1 was overexpressed, purified and crystallized. Crystals of
      native and selenomethionine-substituted PNGM-1 diffracted to 2.10 and 2.30 A
      resolution, respectively. Both the native and the selenomethionine-labelled PNGM
      1 crystals belonged to the monoclinic space group P21, with unit-cell parameters
      a = 122, b = 83, c = 163 A, beta = 110 degrees . Matthews coefficient (VM)
      calculations suggested the presence of 6-10 molecules in the asymmetric unit,
      corresponding to a solvent content of ~31-58%. Structure determination is
      currently in progress.

PMID- 30279318
TI  - Comparative structure analysis of the ETSi domain of ERG3 and its complex with
      the E74 promoter DNA sequence.
AB  - ERG3 (ETS-related gene) is a member of the ETS (erythroblast transformation
      specific) family of transcription factors, which contain a highly conserved DNA
      binding domain. The ETS family of transcription factors differ in their binding
      to promoter DNA sequences, and the mechanism of their DNA-sequence discrimination
      is little known. In the current study, crystals of the ETSi domain (the ETS
      domain of ERG3 containing a CID motif) in space group P41212 and of its complex
      with the E74 DNA sequence (DNA9) in space group C2221 were obtained and their
      structures were determined. Comparative structure analysis of the ETSi domain and
      its complex with DNA9 with previously determined structures of the ERGi domain
      (the ETS domain of ERG containing inhibitory motifs) in space group P65212 and of
      the ERGi-DNA12 complex in space group P41212 were performed. The ETSi domain is
      observed as a homodimer in solution as well as in the crystallographic asymmetric
      unit. Superposition of the structure of the ETSi domain on that of the ERGi
      domain showed a major conformational change at the C-terminal DNA-binding
      autoinhibitory (CID) motif, while minor changes are observed in the loop regions
      of the ETSi-domain structure. The ETSi-DNA9 complex in space group C2221 forms a
      structure that is quite similar to that of the ERG-DNA12 complex in space group
      P41212. Upon superposition of the complexes, major conformational changes are
      observed at the 5' and 3' ends of DNA9, while the conformation of the core GGA
      nucleotides was quite conserved. Comparison of the ETSi-DNA9 structure with known
      structures of ETS class 1 protein-DNA complexes shows the similarities and
      differences in the promoter DNA binding and specificity of the class 1 ETS
      proteins.

PMID- 30279317
TI  - Crystal structures of green fluorescent protein with the unnatural amino acid 4
      nitro-L-phenylalanine.
AB  - The X-ray crystal structures of two superfolder green fluorescent protein (sfGFP)
      constructs containing a genetically incorporated spectroscopic reporter unnatural
      amino acid, 4-nitro-L-phenylalanine (pNO2F), at two unique sites in the protein
      have been determined. Amber codon-suppression methodology was used to site
      specifically incorporate pNO2F at a solvent-accessible (Asp133) and a partially
      buried (Asn149) site in sfGFP. The Asp133pNO2F sfGFP construct crystallized with
      two molecules per asymmetric unit in space group P3221 and the crystal structure
      was refined to 2.05 A resolution. Crystals of Asn149pNO2F sfGFP contained one
      molecule of sfGFP per asymmetric unit in space group P4122 and the structure was
      refined to 1.60 A resolution. The alignment of Asp133pNO2F or Asn149pNO2F sfGFP
      with wild-type sfGFP resulted in small root-mean-square deviations, illustrating
      that these residues do not significantly alter the protein structure and
      supporting the use of pNO2F as an effective spectroscopic reporter of local
      protein structure and dynamics.

PMID- 30279319
TI  - Re-refinement of Plasmodium falciparum orotidine 5'-monophosphate decarboxylase
      provides a clearer picture of an important malarial drug target.
AB  - The development of antimalarial drugs remains a public health priority, and the
      orotidine 5'-monophosphate decarboxylase from Plasmodium falciparum (PfOMPDC) has
      great potential as a drug target. The crystallization of PfOMPDC with substrate
      bound represents an important advance for structure-based drug-design efforts
      [Tokuoka et al. (2008), J. Biochem. 143, 69-78]. The complex of the enzyme bound
      to the substrate OMP (PDB entry 2za1) would be of particular utility in this
      regard. However, re-refinement of this structure of the Michaelis complex shows
      that the bound ligand is the product rather than the substrate. Here, the re
      refinement of a set of three structures, the apo enzyme and two versions of the
      product-bound form (PDB entries 2za1, 2za2 and 2za3), is reported. The improved
      geometry and fit of these structures to the observed electron density will
      enhance their utility in antimalarial drug design.

PMID- 30279320
TI  - X-ray structure of Arthrobacter globiformis M30 ketose 3-epimerase for the
      production of D-allulose from D-fructose.
AB  - The X-ray structure of ketose 3-epimerase from Arthrobacter globiformis M30,
      which was previously reported to be a D-allulose 3-epimerase (AgD-AE), was
      determined at 1.96 A resolution. The crystal belonged to the hexagonal space
      group P6522, with unit-cell parameters a = b = 103.98, c = 256.53 A. The
      structure was solved by molecular replacement using the structure of
      Mesorhizobium loti L-ribulose 3-epimerase (MlL-RE), which has 41% sequence
      identity, as a search model. A hexagonal crystal contained two molecules in the
      asymmetric unit, and AgD-AE formed a homotetramer with twofold symmetry. The
      overall structure of AgD-AE was more similar to that of MlL-RE than to the known
      structures of D-psicose (alternative name D-allulose) 3-epimerases (D-PEs or D
      AEs), although AgD-AE and MlL-RE have different substrate specificities. Both AgD
      AE and MlL-RE have long helices in the C-terminal region that would contribute to
      the stability of the homotetramer. AgD-AE showed higher enzymatic activity for L
      ribulose than D-allulose; however, AgD-AE is stable and is a unique useful enzyme
      for the production of D-allulose from D-fructose.

PMID- 30279321
TI  - Redox manipulation of the manganese metal in human manganese superoxide dismutase
      for neutron diffraction.
AB  - Human manganese superoxide dismutase (MnSOD) is one of the most significant
      enzymes in preventing mitochondrial dysfunction and related diseases by combating
      reactive oxygen species (ROS) in the mitochondrial matrix. Mitochondria are the
      source of up to 90% of cellular ROS generation, and MnSOD performs its necessary
      bioprotective role by converting superoxide into oxygen and hydrogen peroxide.
      This vital catalytic function is conducted via cyclic redox reactions between the
      substrate and the active-site manganese using proton-coupled electron transfers.
      Owing to protons being difficult to detect experimentally, the series of proton
      transfers that compose the catalytic mechanism of MnSOD are unknown. Here,
      methods are described to discern the proton-based mechanism using chemical
      treatments to control the redox state of large perdeuterated MnSOD crystals and
      subsequent neutron diffraction. These methods could be applicable to other
      crystal systems in which proton information on the molecule in question in
      specific chemical states is desired.

PMID- 30279322
TI  - Fluorescence Tumor-Imaging Using a Thermo-Responsive Molecule with an Emissive
      Aminoquinoline Derivative.
AB  - We synthesized (2,4-trifluoromethyl-7-N-bis(2,5,8,11-tetraoxatridecane-13-yl)
      aminoquinoline) TFMAQ-diEg4, an emissive aminoquinoline derivative that
      incorporated two tetraethyleneglycol chains into an amino group. TFMAQ-diEg4
      showed fluorescence and thermo-responsive properties accompanied by a lower
      critical solution temperature (LCST), due to the introduction of the
      oligoethylene glycol chain. This thermo-responsive LCST behavior occurred at the
      border of a cloud point. Below and above the cloud point, self-assemblies of 6-7
      nm nanoparticles and ~2000-nm microparticles were observed, in vitro. In
      addition, TFMAQ-diEg4 showed a high solubility, over 20 mM for aqueous solution,
      in vivo, which not only prevented thrombosis but also allowed various
      examinations, such as single intravenous administration and intravenous drips.
      Intravenous administration of TFMAQ-diEg4, to tumor-bearing, mice led to the
      accumulation of the molecule in the tumor tissue, as observed by fluorescence
      imaging. A subset of mice was treated with local heat around their tumor tissue
      and an intravenous drip of TFMAQ-diEg4, which led to a high intensity of TFMAQ
      diEg4 emission within the tumor tissue. Therefore, we revealed that TFMAQ-diEg4
      was useful as a fluorescence probe with thermo-responsive properties.

PMID- 30279323
TI  - Optimization of Polyphenol Extraction from Allium ampeloprasum var. porrum
      through Response Surface Methodology.
AB  - Allium ampeloprasum var. porrum has been recognized as a rich source of secondary
      metabolites, including phenolic acids, flavonoids and flavonoid polymers
      (proanthocyanidins or condensed tannins), with related health benefits. Both
      parts of Allium ampeloprasum var. porrum (white bulb and pseudostem) are
      traditionally consumed either as a vegetable or as a condiment in many
      Mediterranean countries. The aim of the present study was to optimize the
      extraction conditions of polyphenols from white leek stem and green leek leaf by
      implementing a Box-Behnken design (BBD). The optimization considered basic
      factors affecting extraction efficiency, including extraction time, solvent to
      plant material ratio and solvent mixture composition. Maximum polyphenol yield
      was achieved at an extraction time of 80 and 100 min for white leek stem and
      green leek leaf extracts respectively, solvent to plant material ratio of 5:1
      (v/w) and methanol to water ratio of 40:60 (v/v), for both leek extracts.
      Interestingly, higher total phenolic content was found in green leek leaf
      extracts compared to white leek stem extracts, due to a possible relationship
      between polyphenol production and sunlight radiation. High correlation values
      were also observed between total phenolic content and antioxidant-antiradical
      activity of optimized leek extracts.

PMID- 30279325
TI  - An Alternative Perspective for the Theory of Biological Control.
AB  - Importation biological control represents the planned introduction of a
      specialist natural enemy from the region of origin of an invasive pest or weed.
      For this study, the author considered why attempts to develop a predictive theory
      for biological control have been misguided and what future directions might be
      more promising and effective. Despite considerable interest in the theory of
      consumer-resource population dynamics, such theory has contributed little to
      improvements in the success of biological control due to a focus on persistence
      and equilibrium dynamics rather than establishment and impact. A broader
      consideration of invasion biology in addition to population ecology offers new
      opportunities for a more inclusive theory of biological control that incorporates
      the demographic and genetic processes that more specifically address the
      establishment and impact of introduced natural enemies. The importance of
      propagule size and genetic variance for successful establishment, and of
      contributions to host population growth, relative population growth rates,
      interaction strength, and coevolution for suppression of host abundance are
      discussed as promising future directions for a theory of biological control.

PMID- 30279324
TI  - Preparation and Enrichment Properties of Magnetic Dodecyl Chitosan/Silica
      Composite for Emerging Bisphenol Contaminants.
AB  - Magnetic dodecyl chitosan/silica composite was synthesized and characterized for
      the enrichment of emerging bisphenol contaminants. The result demonstrated that
      bispehnol A, bisphenol AF, bisphenol F, and bisphenol S can be efficiently
      extracted via the resulting composite from aqueous solution. The adsorption rate
      of four investigated bisphenols on the resulting composite was achieved in the
      range of 87-99% within 15 min. Bispehnol A was taken as a representative
      adsorbate to investigate the adsorption studies in detail. The hydrophobic
      interaction was proposed as the principal mechanism for the adsorption of BPs.
      The satisfactory reusability of the resulting composite can be quickly achieved
      by magnetic separation technologies. Magnetic dodecyl chitosan/silica composite
      has a potential to be applied as a type of efficient and easily recyclable
      sorbent for the removal of trace organic pollutants from aqueous sample.

PMID- 30279326
TI  - A Water-Soluble Extract from Actinidia arguta Ameliorates Psoriasis-Like Skin
      Inflammation in Mice by Inhibition of Neutrophil Infiltration.
AB  - Psoriasis is a chronic inflammatory disease with complex etiology involving
      multiple factors. Current treatment methods are highly limited and there is a
      strong need for the development of safer and efficacious agents. We have
      previously shown that a water-soluble extract derived from hardy kiwifruit
      Actinidia arguta, called PG102, shows potent anti-inflammatory effects. Based on
      its reported biological activities, the effects of PG102 were examined on
      imiquimod-induced psoriasis-like skin inflammation. Our results showed that
      topical application of PG102 ameliorates clinical symptoms of psoriasis, reducing
      skin thickness and Interleukin (IL)-17A level in draining lymph nodes without
      causing any adverse effects. Treatment with PG102 on cytokine-stimulated HaCaT
      cells suppressed hyperproliferation and downregulated the expression of various
      chemokines and antimicrobial peptides known to induce neutrophil infiltration.
      These anti-inflammatory activities of PG102 were mediated via inhibition of NF
      kappaB and signal transducer of activation (STAT) signaling. We also found
      decreased neutrophil chemotaxis both in vitro and in vivo. Taken together, PG102
      has potential as a safe and effective reagent for the treatment of psoriasis.

PMID- 30279327
TI  - An Improved Method for Prediction of Cancer Prognosis by Network Learning.
AB  - Accurate identification of prognostic biomarkers is an important yet challenging
      goal in bioinformatics. Many bioinformatics approaches have been proposed for
      this purpose, but there is still room for improvement. In this paper, we propose
      a novel machine learning-based method for more accurate identification of
      prognostic biomarker genes and use them for prediction of cancer prognosis. The
      proposed method specifies the candidate prognostic gene module by graph learning
      using the generative adversarial networks (GANs) model, and scores genes using a
      PageRank algorithm. We applied the proposed method to multiple-omics data that
      included copy number, gene expression, DNA methylation, and somatic mutation data
      for five cancer types. The proposed method showed better prediction accuracy than
      did existing methods. We identified many prognostic genes and their roles in
      their biological pathways. We also showed that the genes identified from
      different omics data were complementary, which led to improved accuracy in
      prediction using multi-omics data.

PMID- 30279328
TI  - Dietary Iron Overload Abrogates Chemically-Induced Liver Cirrhosis in Rats.
AB  - Chronic liver disease is an intractable disease, which can progress to cirrhosis
      and hepatocellular carcinoma. Hepatic iron overload is considered to be involved
      in the progression of chronic liver diseases; however, the mechanism remains to
      be elucidated. Here we investigate the role of dietary iron overload using
      chemically-induced liver cirrhosis model. Rats were fed a high-iron or standard
      diet and were injected intraperitoneally with thioacetamide (TAA) or saline twice
      a week for 20 weeks. Rats with TAA treatment (TAA group) had progressive liver
      cirrhosis characterized by persistent hepatocellular injury, mononuclear cell
      inflammation and bridging fibrosis; these lesions were markedly reduced in rats
      with iron feeding and TAA treatment (Fe-TAA group). Rats with iron feeding alone
      (Fe group) had no evidence of liver injury. Hepatic expression of cleaved caspase
      3, but not phospho-RIP3, was decreased in Fe-TAA group compared with that in TAA
      group. The number of TUNEL-positive (terminal deoxynucleotidyl transferase dUTP
      nick end labeling) apoptotic hepatocytes was lower in the Fe-TAA group than in
      the TAA group. Hepatic xenobiotic metabolism and lipid peroxidation were shown to
      be less related to the abrogation of liver cirrhosis. Our results suggested that
      dietary hepatic iron overload abrogates chemically-induced liver cirrhosis in
      rats, which could partly involve decreased hepatocellular apoptosis.

PMID- 30279329
TI  - Novel Anti-Obesity Properties of Palmaria mollis in Zebrafish and Mouse Models.
AB  - (1) Background: The red seaweed Palmaria mollis (PM), which has a bacon-like
      taste, is increasingly being included in Western diets. In this study, we
      evaluate anti-obesity effects of PM using diet-induced obese (DIO) zebrafish and
      mice models. (2) Methods: We fed PM-containing feed to DIO-zebrafish and mice,
      and evaluated the anti-obesity effects We also analyzed gene expression changes
      in their liver and visceral adipose tissues (VAT). (3) Results: PM ameliorated
      several anti-obesity traits in both animals, including dyslipidaemia, hepatic
      steatosis, and visceral adiposity. In liver tissues of DIO-zebrafish and mice, PM
      upregulated gene expressions involved in peroxisome proliferator-activated
      receptor alpha (PPARA) pathways, and downregulated peroxisome proliferator
      activated receptor gamma (PPARG) pathways, suggesting that the lipid-lowering
      effect of PM might be caused by activation of beta-oxidation and inhibition of
      lipogenesis. In VAT, PM downregulated genes involved in early and late adipocyte
      differentiation in zebrafish, but not in mice. (4) Conclusions: We have
      demonstrated that PM can prevent hepatic steatosis and visceral adiposity for the
      first time. Dietary supplementation of PM as a functional food may be suitable
      for obesity prevention and reduction in the prevalence of obesity-related
      diseases.

PMID- 30279330
TI  - MicroRNA-Attenuated Virus Vaccines.
AB  - Live-attenuated vaccines are the most effective way to establish robust, long
      lasting immunity against viruses. However, the possibility of reversion to wild
      type replication and pathogenicity raises concerns over the safety of these
      vaccines. The use of host-derived microRNAs (miRNAs) to attenuate viruses has
      been accomplished in an array of biological contexts. The broad assortment of
      effective tissue- and species-specific miRNAs, and the ability to target a virus
      with multiple miRNAs, allow for targeting to be tailored to the virus of
      interest. While escape is always a concern, effective strategies have been
      developed to improve the safety and stability of miRNA-attenuated viruses. In
      this review, we discuss the various approaches that have been used to engineer
      miRNA-attenuated viruses, the steps that have been taken to improve their safety,
      and the potential use of these viruses as vaccines.

PMID- 30279331
TI  - Artificial Intelligence in Drug Design.
AB  - Artificial Intelligence (AI) plays a pivotal role in drug discovery. In
      particular artificial neural networks such as deep neural networks or recurrent
      networks drive this area. Numerous applications in property or activity
      predictions like physicochemical and ADMET properties have recently appeared and
      underpin the strength of this technology in quantitative structure-property
      relationships (QSPR) or quantitative structure-activity relationships (QSAR).
      Artificial intelligence in de novo design drives the generation of meaningful new
      biologically active molecules towards desired properties. Several examples
      establish the strength of artificial intelligence in this field. Combination with
      synthesis planning and ease of synthesis is feasible and more and more automated
      drug discovery by computers is expected in the near future.

PMID- 30279332
TI  - Impact of Agaricus bisporus Mushroom Consumption on Gut Health Markers in Healthy
      Adults.
AB  - Eating Agaricus bisporus mushrooms may impact gut health, because they contain
      known prebiotics. This study assessed mushroom consumption compared to meat on
      gastrointestinal tolerance, short chain fatty acid (SCFA) production, laxation,
      and fecal microbiota. A randomized open-label crossover study was conducted in
      healthy adults (n = 32) consuming protein-matched amounts of mushrooms or meat
      twice daily for ten days. Breath hydrogen measures were taken on day one, and
      gastrointestinal tolerance was evaluated throughout treatments. Fecal sample
      collection was completed days 6-10, and samples were assessed for bacterial
      composition, SCFA concentrations, weight, pH, and consistency. There were no
      differences in breath hydrogen, stool frequency, consistency, fecal pH, or SCFA
      concentrations between the two diets. The mushroom diet led to greater overall
      gastrointestinal symptoms than the meat diet on days one and two. The mushroom
      rich diet resulted in higher average stool weight (p = 0.002) and a different
      fecal microbiota composition compared to the meat diet, with greater abundance of
      Bacteroidetes (p = 0.0002) and lower abundance of Firmicutes (p = 0.0009). The
      increase in stool weight and presence of undigested mushrooms in stool suggests
      that mushroom consumption may impact laxation in healthy adults. Additional
      research is needed to interpret the health implications of fecal microbiota
      shifts with mushroom feeding.

PMID- 30279333
TI  - Effects of Whole Milk Supplementation on Gut Microbiota and Cardiometabolic
      Biomarkers in Subjects with and without Lactose Malabsorption.
AB  - The aim of this study was to compare the impact of whole milk supplementation on
      gut microbiota and cardiometabolic biomarkers between lactose malabsorbers (LM)
      and absorbers (LA). We performed a pair-wise intervention study of 31 LM and 31
      LA, 1:1 matched by age, sex, body mass index, and daily dairy intake. Subjects
      were required to add 250 mL/day whole milk for four weeks in their routine diet.
      At the beginning and the end of the intervention period, we collected data on gut
      microbiota and cardiometabolic biomarkers. Whole milk supplementation
      significantly increased Actinobacteria (P < 0.01), Bifidobacterium (P < 0.01),
      Anaerostipe (P < 0.01), and Blautia (P = 0.04), and decreased Megamonas (P =
      0.04) in LM, but not LA. Microbial richness and diversity were not affected. The
      fecal levels of short-chain fatty acids (SCFAs) remained stable throughout the
      study. Body fat mass (P < 0.01) and body fat percentage (P < 0.01) reduced in
      both groups, but the changes did not differ between groups. No significant
      differences in other cardiometabolic markers were found between LM and LA. When
      compared with LA, whole milk supplementation could alter the intestinal
      microbiota composition in LM, without significant changes in fecal SCFAs and
      cardiometabolic biomarkers.

PMID- 30279334
TI  - Comparison on Photosynthesis and Antioxidant Defense Systems in Wheat with
      Different Ploidy Levels and Octoploid Triticale.
AB  - To investigate the evolutionary differences of wheat with different ploidy levels
      and octoploid Triticale, photosynthetic capacity, and antioxidant defenses system
      were compared within and between diploid, tetraploid and hexaploid wheat, and
      octoploid Triticale seedlings. The results showed that seed germination rate,
      chlorophyll content, and photochemical activity of photosystems, and the
      activities of antioxidative enzymes in hexaploid wheat and octoploid Triticale
      were significantly higher than in diploid and tetraploid wheat. Compared to other
      two wheat species and octoploid Triticale, hexaploid wheat presented lower levels
      of reactive oxygen species (ROS). Furthermore, we found that the levels of
      photosystem II reaction center protein D1, light-harvesting complex II b4 (CP29),
      and D subunit of photosystem I (PsaD) in diploid wheat were significantly lower
      compared with hexaploid wheat and octoploid Triticale. Taken together, we
      concluded that hexaploid wheat and octoploid Triticale have higher photosynthetic
      capacities and better antioxidant systems. These findings indicate that different
      ploidy levels of chromosome probably play an important regulatory role in
      photosystems and antioxidative systems of plants.

PMID- 30279336
TI  - Isolation and Identification of the Five Novel Flavonoids from Genipa americana
      Leaves.
AB  - Genipa americana is a medicinal plant popularly known as "jenipapo", which occurs
      in Brazil and belongs to the Rubiaceae family. It is a species widely distributed
      in the tropical Central and South America, especially in the Cerrado biome. Their
      leaves and fruits are used as food and popularly in folk medicine to treat
      anemias, as an antidiarrheal, and anti-syphilitic. Iridoids are the main
      secondary metabolites described from G. americana, but few studies have been
      conducted with their leaves. In this study, the aim was to chemical approach for
      identify the main compounds present at the extract of G. americana leaves. The
      powdered leaves were extracted by maceration with EtOH: water (70:30, v/v),
      following liquid-liquid partition with petroleum ether, chloroform, ethyl acetate
      and n-butanol. A total of 13 compounds were identified. In addition three
      flavonoids were isolated from the ethyl acetate fraction: quercetin-3-O
      robinoside (GAF 1), kaempferol-3-O-robinoside (GAF 2) and isorhamnetin-3-O
      robinoside (GAF 3) and, from n-butanol fraction more two flavonoids were
      isolated, kaempferol-3-O-robinoside-7-O-rhamnoside (robinin) (GAF 4) and
      isorhamnetin-3-O-robinoside-7-rhamnoside (GAF 5). Chemical structures of these
      five flavonoids were elucidated using spectroscopic methods (MS, 1H and 13C-NMR
      1D and 2D). These flavonoids glycosides were described for the first time in G.
      americana.

PMID- 30279335
TI  - Nutrigenetic Contributions to Dyslipidemia: A Focus on Physiologically Relevant
      Pathways of Lipid and Lipoprotein Metabolism.
AB  - Cardiovascular disease (CVD) remains the number one cause of death worldwide, and
      dyslipidemia is a major predictor of CVD mortality. Elevated lipid concentrations
      are the result of multiple genetic and environmental factors. Over 150 genetic
      loci have been associated with blood lipid levels. However, not all variants are
      present in pathways relevant to the pathophysiology of dyslipidemia. The study of
      these physiologically relevant variants can provide mechanistic understanding of
      dyslipidemia and identify potential novel therapeutic targets. Additionally,
      dietary fatty acids have been evidenced to exert both positive and negative
      effects on lipid profiles. The metabolism of both dietary and endogenously
      synthesized lipids can be affected by individual genetic variation to produce
      elevated lipid concentrations. This review will explore the genetic, dietary, and
      nutrigenetic contributions to dyslipidemia.

PMID- 30279337
TI  - High Throughput Identification of Antihypertensive Peptides from Fish Proteome
      Datasets.
AB  - Antihypertensive peptides (AHTPs) are a group of small peptides with the main
      role to block key enzymes or receptors in the angiotensin genesis pathway. A
      great number of AHTPs have been isolated or digested from natural food resources;
      however, comprehensive studies on comparisons of AHTPs in various species from
      the perspective of big data are rare. Here, we established a simplified local
      AHTP database, and performed in situ mapping for high throughput identification
      of AHTPs with high antihypertensive activity from high-quality whole proteome
      datasets of 18 fish species. In the 35 identified AHTPs with reported high
      activity, we observed that Gly-Leu-Pro, Leu-Pro-Gly, and Val-Ser-Val are the
      major components of fish proteins, and AHTP hit numbers in various species
      demonstrated a similar distributing pattern. Interestingly, Atlantic salmon
      (Salmo salar) is in possession of far more abundant AHTPs compared with other
      fish species. In addition, collagen subunit protein is the largest group with
      more matching AHTPs. Further exploration of two collagen subunits (col4a5 and
      col8a1) in more fish species suggested that the hit pattern of these conserved
      proteins among teleost is almost the same, and their phylogeny is consistent with
      the evolution of these fish species. In summary, our present study provides basic
      information for the relationship of AHTPs with fish proteins, which sheds light
      on rapid discovery of marine drugs or food additives from fish protein
      hydrolysates to alleviate hypertension.

PMID- 30279338
TI  - The Microbiome and Radiation Induced-Bowel Injury: Evidence for Potential
      Mechanistic Role in Disease Pathogenesis.
AB  - Radiotherapy has played a major role in both the curative and palliative
      treatment of cancer patients for decades. However, its toxic effect to the
      surrounding normal healthy tissue remains a major drawback. In cases of intra
      abdominal and/or pelvic malignancy, healthy bowel is inevitably included in the
      radiation field, causing undesirable consequences that subsequently manifest as
      radiation-induced bowel injury, which is associated with significant morbidity
      and mortality. The pathophysiology of radiation-induced bowel injury is poorly
      understood, although we now know that it derives from a complex interplay of
      epithelial injury and alterations in the enteric immune, nervous, and vascular
      systems in genetically predisposed individuals. Furthermore, evidence supporting
      a pivotal role for the gut microbiota in the development of radiation-induced
      bowel injury has been growing. In this review, we aim to appraise our current
      understanding of radiation-induced bowel injury and the role of the microbiome in
      its pathogenesis as well as prevention and treatment. Greater understanding of
      the relationship between the disease mechanism of radiation-induced bowel injury
      and gut microbiome might shed light on potential future prevention and treatment
      strategies through the modification of a patient's gut microbiome.

PMID- 30279340
TI  - Atomic Surface Segregation and Structural Characterization of PdPt Bimetallic
      Nanoparticles.
AB  - Bimetallic nanoparticles are of interest since they lead to many interesting
      electrical, chemical, catalytic, and optical properties. They are particularly
      important in the field of catalysis since they show superior catalytic properties
      than their monometallic counterparts. The structures of bimetallic nanoparticles
      depend mainly on the synthesis conditions and the miscibility of the two
      components. In this work, PdPt alloyed-bimetallic nanoparticles (NPs) were
      synthesized through the polyol method, and characterized using spherical
      aberration (Cs) corrected scanning transmission electron microscopy (STEM). High
      angle annular dark-field (HAADF)-STEM images of bimetallic nanoparticles were
      obtained. The contrast of images shows that nanoparticles have an alloy structure
      with an average size of 8.2 nm. Together with the characterization of
      nanoparticles, a systematic molecular dynamics simulations study focused on the
      structural stability and atomic surface segregation trends in 923-atom PdPt
      alloyed-bimetallic NPs was carried out.

PMID- 30279339
TI  - Annurca Apple Polyphenols Ignite Keratin Production in Hair Follicles by
      Inhibiting the Pentose Phosphate Pathway and Amino Acid Oxidation.
AB  - Patterned hair loss (PHL) affects around 50% of the adult population worldwide.
      The negative impact that this condition exerts on people's life quality has
      boosted the appearance of over-the-counter products endowed with hair-promoting
      activity. Nutraceuticals enriched in polyphenols have been recently shown to
      promote hair growth and counteract PHL. Malus pumila Miller cv. Annurca is an
      apple native to Southern Italy presenting one of the highest contents of
      Procyanidin B2. We have recently shown that oral consumption of Annurca
      polyphenolic extracts (AAE) stimulates hair growth, hair number, hair weight and
      keratin content in healthy human subjects. Despite its activity, the analysis of
      the molecular mechanism behind its hair promoting effect is still partially
      unclear. In this work we performed an unprecedented metabolite analysis of hair
      follicles (HFs) in mice topically treated with AAE. The metabolomic profile,
      based on a high-resolution mass spectrometry approach, revealed that AAE re
      programs murine HF metabolism. AAE acts by inhibiting several NADPH dependent
      reactions. Glutaminolysis, pentose phosphate pathway, glutathione, citrulline and
      nucleotide synthesis are all halted in vivo by the treatment of HFs with AAE. On
      the contrary, mitochondrial respiration, beta-oxidation and keratin production
      are stimulated by the treatment with AAE. The metabolic shift induced by AAE
      spares amino acids from being oxidized, ultimately keeping them available for
      keratin biosynthesis.

PMID- 30279341
TI  - Maternal Melatonin Therapy Attenuates Methyl-Donor Diet-Induced Programmed
      Hypertension in Male Adult Rat Offspring.
AB  - Although pregnant women are advised to consume methyl-donor food, some reports
      suggest an adverse outcome. We investigated whether maternal melatonin therapy
      can prevent hypertension induced by a high methyl-donor diet. Female Sprague
      Dawley rats received either a normal diet, a methyl-deficient diet (L-MD), or a
      high methyl-donor diet (H-MD) during gestation and lactation. Male offspring were
      assigned to four groups (n = 7-8/group): control, L-MD, H-MD, and H-MD rats were
      given melatonin (100 mg/L) with their drinking water throughout the period of
      pregnancy and lactation (H-MD+M). At 12 weeks of age, male offspring exposed to a
      L-MD or a H-MD diet developed programmed hypertension. Maternal melatonin therapy
      attenuated high methyl-donor diet-induced programmed hypertension. A maternal L
      MD diet and H-MD diet caused respectively 938 and 806 renal transcripts to be
      modified in adult offspring. The protective effects of melatonin against
      programmed hypertension relate to reduced oxidative stress, increased urinary NO2
      level, and reduced renal expression of sodium transporters. A H-MD or L-MD diet
      may upset the balance of methylation status, leading to alterations of renal
      transcriptome and programmed hypertension. A better understanding of
      reprogramming effects of melatonin might aid in developing a therapeutic strategy
      for the prevention of hypertension in adult offspring exposed to an excessive
      maternal methyl-supplemented diet.

PMID- 30279342
TI  - Inhibition of Tetraspanin Functions Impairs Human Papillomavirus and
      Cytomegalovirus Infections.
AB  - Tetraspanins are suggested to regulate the composition of cell membrane
      components and control intracellular transport, which leaves them vulnerable to
      utilization by pathogens such as human papillomaviruses (HPV) and
      cytomegaloviruses (HCMV) to facilitate host cell entry and subsequent infection.
      In this study, by means of cellular depletion, the cluster of differentiation
      (CD) tetraspanins CD9, CD63, and CD151 were found to reduce HPV16 infection in
      HeLa cells by 50 to 80%. Moreover, we tested recombinant proteins or peptides of
      specific tetraspanin domains on their effect on the most oncogenic HPV type,
      HPV16, and HCMV. We found that the C-terminal tails of CD63 and CD151
      significantly inhibited infections of both HPV16 and HCMV. Although CD9 was newly
      identified as a key cellular factor for HPV16 infection, the recombinant CD9 C
      terminal peptide had no effect on infection. Based on the determined half-maximal
      inhibitory concentration (IC50), we classified CD63 and CD151 C-terminal peptides
      as moderate to potent inhibitors of HPV16 infection in HeLa and HaCaT cells, and
      in EA.hy926, HFF (human foreskin fibroblast) cells, and HEC-LTT (human
      endothelial cell-large T antigen and telomerase) cells for HCMV, respectively.
      These results indicate that HPV16 and HCMV share similar cellular requirements
      for their entry into host cells and reveal the necessity of the cytoplasmic CD151
      and CD63 C-termini in virus infections. Furthermore, this highlights the
      suitability of these peptides for functional investigation of tetraspanin domains
      and as inhibitors of pathogen infections.

PMID- 30279344
TI  - Preparation and Assessment of Heat-Treated alpha-Chitin Nanowhiskers Reinforced
      Poly(viny alcohol) Film for Packaging Application.
AB  - In this study, poly(vinyl alcohol) (PVA) composite films enhanced by alpha-chitin
      nanowhiskers (ChWs) were prepared through heat treatment. The obtained membranes
      were assessed by means of FTIR spectroscopy, X-ray diffraction, thermogravimetric
      analysis, regular light transmittance, mechanical tests, permeability and water
      absorption. The influence of the nano-component and heat treatment on the
      mechanical, thermal and water-resistant properties of the composite membrane were
      analyzed. From the results of the work, the produced films with excellent barrier
      properties and inexpensive raw processed materials have great prospects in
      packaging applications.

PMID- 30279343
TI  - New N-(oxazolylmethyl)-thiazolidinedione Active against Candida albicans Biofilm:
      Potential Als Proteins Inhibitors.
AB  - C. albicans is the most frequently occurring fungal pathogen, and is becoming an
      increasing public health problem, especially in the context of increased
      microbial resistance. This opportunistic pathogen is characterized by a
      versatility explained mainly by its ability to form complex biofilm structures
      that lead to enhanced virulence and antibiotic resistance. In this context, a
      review of the known C. albicans biofilm formation inhibitors were performed and a
      new N-(oxazolylmethyl)-thiazolidinedione scaffold was constructed. 16 new
      compounds were synthesized and characterized in order to confirm their proposed
      structures. A general antimicrobial screening against Gram-positive and Gram
      negative bacteria, as well as fungi, was performed and revealed that the
      compounds do not have direct antimicrobial activity. The anti-biofilm activity
      evaluation confirmed the compounds act as selective inhibitors of C. albicans
      biofilm formation. In an effort to substantiate this biologic profile, we used in
      silico investigations which suggest that the compounds could act by binding, and
      thus obstructing the functions of, the C. albicans Als surface proteins,
      especially Als1, Als3, Als5 and Als6. Considering the well documented role of
      Als1 and Als3 in biofilm formation, our new class of compounds that target these
      proteins could represent a new approach in C. albicans infection prevention and
      management.

PMID- 30279345
TI  - Post-Exercise Appetite and Ad Libitum Energy Intake in Response to High-Intensity
      Interval Training versus Moderate- or Vigorous-Intensity Continuous Training
      among Physically Inactive Middle-Aged Adults.
AB  - High-intensity interval training (HIIT) is considered a time-efficient exercise
      strategy for weight management. However, data regarding the acute appetite and
      energy intake responses to HIIT versus continuous training remain inconclusive.
      This study investigated the ad libitum energy intake and appetite responses to a
      single session of HIIT versus moderate-intensity continuous training (MICT) and
      vigorous-intensity continuous training (VICT). Using a randomized crossover
      design, 11 middle-aged physically inactive men (45.7 +/- 7.4 years, 23.5 +/- 2.1
      kg m-2) participated in three treadmill trials at 7-day intervals. HIIT comprised
      10 1-min periods at 100% VO2max interspersed with 1-min periods of active
      recovery. MICT comprised a 40-min session at 65% VO2max, while VICT comprised a
      20-min session at 80% VO2max. After each trial, the participants consumed an ad
      libitum buffet meal for which the energy intake was recorded. The participants'
      perceived appetite was assessed before and after exercise sessions using the
      Visual Analogue Scale (VAS). No significant differences in post-exercise ad
      libitum energy intake were observed between trials (HIIT: 645 +/- 262.9 kcal;
      MICT: 614.7 +/- 271.2 kcal; VICT: 623.1 +/- 249.0 kcal, p > 0.05). Although the
      perceived appetite responses exhibited a significant main effect of time (p <
      0.01), no group differences were observed (p > 0.05). In summary, these findings
      suggest that the interval or continuous nature of exercise has no significant
      effect on appetite responses in physically inactive middle-aged adults, at least
      during the short-term post-exercise period.

PMID- 30279346
TI  - Comparative Genomics among Closely Related Streptomyces Strains Revealed
      Specialized Metabolite Biosynthetic Gene Cluster Diversity.
AB  - Specialized metabolites are of great interest due to their possible industrial
      and clinical applications. The increasing number of antimicrobial resistant
      infectious agents is a major health threat and therefore, the discovery of
      chemical diversity and new antimicrobials is crucial. Extensive genomic data from
      Streptomyces spp. confirm their production potential and great importance. Genome
      sequencing of the same species strains indicates that specialized metabolite
      biosynthetic gene cluster (SMBGC) diversity is not exhausted, and instead, a pool
      of novel specialized metabolites still exists. Here, we analyze the genome
      sequence data from six phylogenetically close Streptomyces strains. The results
      reveal that the closer strains are phylogenetically, the number of shared gene
      clusters is higher. Eight specialized metabolites comprise the core metabolome,
      although some strains have only six core gene clusters. The number of conserved
      gene clusters common between the isolated strains and their closest phylogenetic
      counterparts varies from nine to 23 SMBGCs. However, the analysis of these
      phylogenetic relationships is not affected by the acquisition of gene clusters,
      probably by horizontal gene transfer events, as each strain also harbors strain
      specific SMBGCs. Between one and 15 strain-specific gene clusters were
      identified, of which up to six gene clusters in a single strain are unknown and
      have no identifiable orthologs in other species, attesting to the existing SMBGC
      novelty at the strain level.

PMID- 30279349
TI  - Cadmium-Free Quantum Dots as Fluorescent Labels for Exosomes.
AB  - Quantum dots are attractive alternatives to organic fluorophores for the purposes
      of fluorescent labeling and the detection of biomarkers. They can also be made to
      specifically target a protein of interest by conjugating biomolecules, such as
      antibodies. However, the majority of the fluorescent labeling using quantum dots
      is done using toxic materials such as cadmium or lead due to the well-established
      synthetic processes for these quantum dots. Here, we demonstrate the use of
      indium phosphide quantum dots with a zinc sulfide shell for the purposes of
      labeling and the detection of exosomes derived from the THP-1 cell line (monocyte
      cell line). Exosomes are nano-sized vesicles that have the potential to be used
      as biomarkers due to their involvement in complex cell processes. However, the
      lack of standardized methodology around the detection and analysis of exosomes
      has made it difficult to detect these membrane-containing vesicles. We targeted a
      protein that is known to exist on the surface of the exosomes (CD63) using a CD63
      antibody. The antibody was conjugated to the quantum dots that were first made
      water-soluble using a ligand-exchange method. The conjugation was done using
      carbodiimide coupling, and was confirmed using a range of different methods such
      as dynamic light scattering, surface plasmon resonance, fluorescent microscopy,
      and Fourier transform infrared spectroscopy. The conjugation of the quantum dot
      antibody to the exosomes was further confirmed using similar methods. This
      demonstrates the potential for the use of a non-toxic conjugate to target nano
      sized biomarkers that could be further used for the detection of different
      diseases.

PMID- 30279348
TI  - Hospital-Acquired Hyponatremia in Children Following Hypotonic versus Isotonic
      Intravenous Fluids Infusion.
AB  - Hypotonic solutions have been used in pediatrics for maintenance of intravenous
      (IV) hydration. However, recent randomized control trials and cohort studies have
      raised significant concerns for association with hospital-acquired hyponatremia
      (HAH). The study aimed to assess whether the use of hypotonic parenteral
      solutions (PS) compared with isotonic PS is associated with increased HAH risk in
      children with common pediatric conditions. Retrospective chart review of 472
      patients aged 2 months to 18 years who received either isotonic or hypotonic PS
      as maintenance fluids. Administration of hypotonic PS was associated with a four
      fold increase in risk of developing HAH in the univariate analysis, (unadjusted
      odds ratio (OR) = 3.99; 95% confidence interval (CI): 1.36-11.69, p = 0.01).
      Hypotonic PS were associated with HAH (p = 0.04) when adjusted for the level of
      admission serum CO2. There was a mean decrease of serum sodium of 0.53 mEq/L in
      the hypotonic group compared to the mean increase of 4.88 mEq/L in the isotonic
      group. These data suggest that hypotonic PS are associated with HAH in children
      admitted for common pediatric conditions. Isotonic PS should be considered as a
      safer choice for maintenance fluid hydration.

PMID- 30279350
TI  - Hand Laser Perfusion Imaging to Assess Radial Artery Patency: A Pilot Study.
AB  - OBJECTIVES: To test a novel diagnostic technique to assess radial artery
      perfusion after transradial catheterization. BACKGROUND: Despite being mostly
      asymptomatic, radial artery occlusion (RAO) is not a benign complication, and its
      diagnosis is frequently missed because it requires time-consuming diagnostic
      testing. We developed a novel operator-independent diagnostic test to assess RAO
      after coronary procedures through a transradial access (TRA) by means of hand
      Laser Perfusion Imaging (LPI). METHODS: One hundred patients were evaluated
      before and after TRA by means of the LPI. A radial perfusion index (RPI) was
      calculated as the ratio between the total perfusion measured during ulnar
      occlusion and total basal perfusion. Vascular Duplex scan (VDS) was used as the
      standard of reference to assess the artery patency. RESULTS: LPI correctly
      identified RAO in 100% of cases. Post-procedural RPI was 0.89 +/- 0.13 in
      patients with radial patency vs. 0.15 +/- 0.04 in patients with RAO (p < 0.001).
      In line with these results, ROC analysis showed an excellent diagnostic
      performance of the LPI, that correctly identified all RAO cases (Area Under the
      Curve, AUC = 1.0; p < 0.001), with an optimal diagnostic cutoff at 0.2 RPI.
      CONCLUSIONS: LPI is a reliable diagnostic technique for RAO, offering the
      advantages of being quick and simple to perform.

PMID- 30279351
TI  - Structural Optimization of Foldamer-Dendrimer Conjugates as Multivalent Agents
      against the Toxic Effects of Amyloid Beta Oligomers.
AB  - Alzheimer's disease is one of the most common chronic neurodegenerative
      disorders. Despite several in vivo and clinical studies, the cause of the disease
      is poorly understood. Currently, amyloid beta (Abeta) peptide and its tendency to
      assemble into soluble oligomers are known as a main pathogenic event leading to
      the interruption of synapses and brain degeneration. Targeting neurotoxic Abeta
      oligomers can help recognize the disease at an early stage or it can be a
      potential therapeutic approach. Unnatural beta-peptidic foldamers are
      successfully used against many different protein targets due to their favorable
      structural and pharmacokinetic properties compared to small molecule or protein
      like drug candidates. We have previously reported a tetravalent foldamer
      dendrimer conjugate which can selectively bind Abeta oligomers. Taking advantage
      of multivalency and foldamers, we synthesized different multivalent foldamer
      based conjugates to optimize the geometry of the ligand. Isothermal titration
      calorimetry (ITC) was used to measure binding affinity to Abeta, thereafter 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based tissue
      viability assay and impedance-based viability assay on SH-SY5Y cells were applied
      to monitor Abeta toxicity and protective effects of the compounds. Important
      factors for high binding affinity were determined and a good correlation was
      found between influencing the valence and the capability of the conjugates for
      Abeta binding.

PMID- 30279347
TI  - Oncogenic Signaling Induced by HCV Infection.
AB  - The liver is frequently exposed to toxins, metabolites, and oxidative stress,
      which can challenge organ function and genomic stability. Liver regeneration is
      therefore a highly regulated process involving several sequential signaling
      events. It is thus not surprising that individual oncogenic mutations in
      hepatocytes do not necessarily lead to cancer and that the genetic profiles of
      hepatocellular carcinomas (HCCs) are highly heterogeneous. Long-term infection
      with hepatitis C virus (HCV) creates an oncogenic environment by a combination of
      viral protein expression, persistent liver inflammation, oxidative stress, and
      chronically deregulated signaling events that cumulate as a tipping point for
      genetic stability. Although novel direct-acting antivirals (DAA)-based treatments
      efficiently eradicate HCV, the associated HCC risk cannot be fully eliminated by
      viral cure in patients with advanced liver disease. This suggests that HCV may
      persistently deregulate signaling pathways beyond viral cure and thereby continue
      to perturb cancer-relevant gene function. In this review, we summarize the
      current knowledge about oncogenic signaling pathways derailed by chronic HCV
      infection. This will not only help to understand the mechanisms of
      hepatocarcinogenesis but will also highlight potential chemopreventive strategies
      to help patients with a high-risk profile of developing HCC.

PMID- 30279353
TI  - Resistance of Superhydrophobic Surface-Functionalized TiO2 Nanotubes to Corrosion
      and Intense Cavitation.
AB  - The availability of robust superhydrophobic materials with the ability to
      withstand harsh environments are in high demand for many applications. In this
      study, we have presented a simple method to fabricate superhydrophobic materials
      from TiO2 nanotube arrays (TNTAs) and investigated the resilience of the
      materials when they are subjected to harsh conditions such as intense cavitation
      upon ultrasonication, corrosion in saline water, water-jet impact, and abrasion.
      The TNTAs were prepared by anodization of Ti foil in buffered aqueous electrolyte
      containing fluoride ions. The hydrophilic TNTAs were functionalized with
      octadecylphosphonic acid (ODPA) or 1H, 1H', 2H, 2H'-perfluorodecyl phosphonic
      acid (PFDPA) to form a self-assembled monolayer on the TNTA surface to produce
      superhydrophobic ODPA@TNTA or PFDPA@TNTA surfaces. The superhydrophobic ODPA@TNTA
      and PFDPA@TNTA have contact angles of 156.0 degrees  +/- 1.5 degrees  and 168
      degrees  +/- 1.5 degrees , and contact angle hysteresis of 3.0 degrees  and 0.8
      degrees , respectively. The superhydrophobic ODPA@TNTA and PFDPA@TNTA were
      subjected to ultrasonication, corrosion in saline water, and water-jet impact and
      abrasion, and the resilience of the systems was characterized by electrochemical
      impedance spectroscopy (EIS), contact angle (CA) measurements, diffuse
      reflectance Fourier transform infrared spectroscopy (DRIFTS), and field-emission
      scanning electron microscopy (FESEM). The results presented here show that
      superhydrophobic ODPA@TNTA and PFDPA@TNTA are robust and resilient under the
      harsh conditions studied in this work, and indicate the potential of these
      materials to be deployed in practical applications.

PMID- 30279355
TI  - Impact of Genomics on Clarifying the Evolutionary Relationships amongst
      Mycobacteria: Identification of Molecular Signatures Specific for the
      Tuberculosis-Complex of Bacteria with Potential Applications for Novel
      Diagnostics and Therapeutics.
AB  - An alarming increase in tuberculosis (TB) caused by drug-resistant strains of
      Mycobacterium tuberculosis has created an urgent need for new antituberculosis
      drugs acting via novel mechanisms. Phylogenomic and comparative genomic analyses
      reviewed here reveal that the TB causing bacteria comprise a small group of
      organisms differing from all other mycobacteria in numerous regards.
      Comprehensive analyses of protein sequences from mycobacterial genomes have
      identified 63 conserved signature inserts and deletions (indels) (CSIs) in
      important proteins that are distinctive characteristics of the TB-complex of
      bacteria. The identified CSIs provide potential means for development of novel
      diagnostics as well as therapeutics for the TB-complex of bacteria based on four
      key observations: (i) The CSIs exhibit a high degree of exclusivity towards the
      TB-complex of bacteria; (ii) Earlier work on CSIs provide evidence that they play
      important/essential functions in the organisms for which they exhibit
      specificity; (iii) CSIs are located in surface-exposed loops of the proteins
      implicated in mediating novel interactions; (iv) Homologs of the CSIs containing
      proteins, or the CSIs in such homologs, are generally not found in humans. Based
      on these characteristics, it is hypothesized that the high-throughput virtual
      screening for compounds binding specifically to the CSIs (or CSI containing
      regions) and thereby inhibiting the cellular functions of the CSIs could lead to
      the discovery of a novel class of drugs specifically targeting the TB-complex of
      organisms.

PMID- 30279352
TI  - The Effect of Aspergillus Thermomutatus Chrysovirus 1 on the Biology of Three
      Aspergillus Species.
AB  - This study determined the effects of Aspergillus thermomutatus chrysovirus 1
      (AthCV1), isolated from Aspergillus thermomutatus, on A. fumigatus, A. nidulans
      and A. niger. Protoplasts of virus-free isolates of A. fumigatus, A. nidulans and
      A. niger were transfected with purified AthCV1 particles and the phenotype,
      growth and sporulation of the isogenic AthCV1-free and AthCV1-infected lines
      assessed at 20  degrees C and 37  degrees C and gene expression data collected at
      37  degrees C. AthCV1-free and AthCV1-infected A. fumigatus produced only conidia
      at both temperatures but more than ten-fold reduced compared to the AthCV1
      infected line. Conidiation was also significantly reduced in infected lines of A.
      nidulans and A. niger at 37  degrees C. AthCV1-infected lines of A. thermomutatus
      and A. nidulans produced large numbers of ascospores at both temperatures,
      whereas the AthCV1-free line of the former did not produce ascospores. AthCV1
      infected lines of all species developed sectoring phenotypes with sclerotia
      produced in aconidial sectors of A. niger at 37  degrees C. AthCV1 was detected
      in 18% of sclerotia produced by AthCV1-infected A. niger and 31% of ascospores
      from AthCV1-infected A. nidulans. Transcriptome analysis of the naturally AthCV1
      infected A. thermomutatus and the three AthCV1-transfected Aspergillus species
      showed altered gene expression as a result of AthCV1-infection. The results
      demonstrate that AthCV1 can infect a range of Aspergillus species resulting in
      reduced sporulation, a potentially useful attribute for a biological control
      agent.

PMID- 30279354
TI  - Effects of Polyacrylic Acid Pre-Treatment on Bonded-Dentine Interfaces Created
      with a Modern Bioactive Resin-Modified Glass Ionomer Cement and Subjected to
      Cycling Mechanical Stress.
AB  - OBJECTIVES: Resin-modified glass ionomer cements (RMGIC) are considered excellent
      restorative materials with unique therapeutic and anti-cariogenic activity.
      However, concerns exist regarding the use of polyacrylic acid as a dentine
      conditioner as it may influence the bonding performance of RMGIC. The aim of this
      study was to evaluate the effect of different protocols for cycling mechanical
      stress on the bond durability and interfacial ultramorphology of a modern RMGIC
      applied to dentine pre-treated with/without polyacrylic acid conditioner (PAA).
      METHODS: The RMGIC was applied onto human dentine specimens prepared with silicon
      carbide (SiC) abrasive paper with or without the use of a PAA conditioner. The
      specimens were immersed in deionised water for 24 h then divided in 3 groups. The
      first group was cut into matchsticks (cross-sectional area of 0.9 mm2) and tested
      immediately for microtensile bond strength (MTBS). The second was first subjected
      to load cycling (250,000 cycles; 3 Hz; 70 N) and then cut into matchsticks and
      tested for MTBS. The third group was subjected to load cycling (250,000 cycles; 3
      Hz; 70 N), cut into matchsticks, and then immersed for 8 months storage in
      artificial saliva (AS); these were finally tested for MTBS. The results were
      analysed statistically using two-way ANOVA and the Student-Newman-Keuls test
      (alpha = 0.05). Fractographic analysis was performed using FE-SEM, while further
      RMCGIC-bonded dentine specimens were aged as previously described and used for
      interfacial ultramorphology characterisation (dye nanoleakage) using confocal
      microscopy. RESULTS: The RMGIC applied onto dentine that received no pre
      treatment (10% PAA gel) showed no significant reduction in MTBS after load
      cycling followed by 8 months of storage in AS (p > 0.05). The RMGIC-dentine
      interface created in PAA-conditioned SiC-abraded dentine specimens showed no sign
      of degradation, but with porosities within the bonding interface both after load
      cycling and after 8 months of storage in AS. Conversely, the RMGIC-dentine
      interface of the specimens with no PAA pre-treatment showed no sign of porosity
      within the interface after any of the aging protocols, although some bonded
      dentine interfaces presented cohesive cracks within the cement after prolonged AS
      storage. However, the specimens of this group showed no significant reduction in
      bond strength (p < 0.05) after 8 months of storage in AS or load cycling (p >
      0.05). After prolonged AS storage, the bond strength value attained in RMGIC
      dentine specimens created in PAA pre-treated dentine were significantly higher
      than those observed in the specimens created with no PAA pre-treatment in
      dentine. CONCLUSIONS: PAA conditioning of dentine prior to application of RMGIC
      induces no substantial effect on the bond strength after short-term storage, but
      its use may increase the risk of collagen degradation at the bonding interface
      after prolonged aging. Modern RMGIC applied without PAA dentine pre-treatment may
      have greater therapeutic synergy with saliva during cycle occlusal load, thereby
      enhancing the remineralisation and protection of the bonding interface.

PMID- 30279357
TI  - Genetic Abnormalities, Clonal Evolution, and Cancer Stem Cells of Brain Tumors.
AB  - Brain tumors are highly heterogeneous and have been classified by the World
      Health Organization in various histological and molecular subtypes. Gliomas have
      been classified as ranging from low-grade astrocytomas and oligodendrogliomas to
      high-grade astrocytomas or glioblastomas. These tumors are characterized by a
      peculiar pattern of genetic alterations. Pediatric high-grade gliomas are
      histologically indistinguishable from adult glioblastomas, but they are
      considered distinct from adult glioblastomas because they possess a different
      spectrum of driver mutations (genes encoding histones H3.3 and H3.1).
      Medulloblastomas, the most frequent pediatric brain tumors, are considered to be
      of embryonic derivation and are currently subdivided into distinct subgroups
      depending on histological features and genetic profiling. There is emerging
      evidence that brain tumors are maintained by a special neural or glial stem cell
      like population that self-renews and gives rise to differentiated progeny. In
      many instances, the prognosis of the majority of brain tumors remains negative
      and there is hope that the new acquisition of information on the molecular and
      cellular bases of these tumors will be translated in the development of new, more
      active treatments.

PMID- 30279356
TI  - Rice Routes of Countering Xanthomonas oryzae.
AB  - Bacterial blight (BB) and bacterial leaf streak (BLS), caused by Xanthomonas
      oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola, respectively, are two
      devastating diseases in rice planting areas worldwide. It has been proven that
      adoption of rice resistance is the most effective, economic, and environment
      friendly strategy to avoid yield loss caused by BB and BLS. As a model system for
      plant-pathogen interaction, the rice-X. oryzae pathosystem has been intensively
      investigated in the past decade. Abundant studies have shown that the resistance
      and susceptibility of rice to X. oryzae is determined by molecular interactions
      between rice genes or their products and various pathogen effectors. In this
      review, we briefly overviewed the literature regarding the diverse interactions,
      focusing on recent advances in uncovering mechanisms of rice resistance and X.
      oryzae virulence. Our analysis and discussions will not only be helpful for
      getting a better understanding of coevolution of the rice innate immunity and X.
      oryzae virulence, but it will also provide new insights for application of plant
      R genes in crop breeding.

PMID- 30279359
TI  - Antimicrobial and Antibiofilm Activity of a Recombinant Fragment of beta-Thymosin
      of Sea Urchin Paracentrotus lividus.
AB  - With the aim to obtain new antimicrobials against important pathogens such as
      Staphylococcus aureus and Pseudomonas aeruginosa, we focused on antimicrobial
      peptides (AMPs) from Echinoderms. An example of such peptides is Paracentrin 1
      (SP1), a chemically synthesised peptide fragment of a sea urchin thymosin. In the
      present paper, we report on the biological activity of a Paracentrin 1 derivative
      obtained by recombination. The recombinant paracentrin RP1, in comparison to the
      synthetic SP1, is 22 amino acids longer and it was considerably more active
      against the planktonic forms of S. aureus ATCC 25923 and P. aeruginosa ATCC 15442
      at concentrations of 50 ug/mL. Moreover, it was able to inhibit biofilm formation
      of staphylococcal and P. aeruginosa strains at concentrations equal to 5.0 and
      10.7 ug/mL, respectively. Molecular dynamics (MD) simulations allowed to
      rationalise the results of the experimental investigations, providing atomistic
      insights on the binding of RP1 toward models of mammalian and bacterial cell
      membranes. Overall, the results obtained point out that RP1 shows a remarkable
      preference for bacterial membranes, in excellent agreement with the antibacterial
      activity, highlighting the promising potential of using the tested peptide as a
      template for the development of novel antimicrobial agents.

PMID- 30279358
TI  - A Systematic Review of Access to Rehabilitation for People with Disabilities in
      Low- and Middle-Income Countries.
AB  - Rehabilitation seeks to optimize functioning of people with impairments and
      includes a range of specific health services-diagnosis, treatment, surgery,
      assistive devices, and therapy. Evidence on access to rehabilitation services for
      people with disabilities in low- and middle-income countries (LMICs) is limited.
      A systematic review was conducted to examine this in depth. In February 2017, six
      databases were searched for studies measuring access to rehabilitation among
      people with disabilities in LMICs. Eligible measures of access to rehabilitation
      included: use of assistive devices, use of specialist health services, and
      adherence to treatment. Two reviewers independently screened titles, abstracts,
      and full texts. Data was extracted by one reviewer and checked by a second. Of
      13,048 screened studies, 77 were eligible for inclusion. These covered a broad
      geographic area. 17% of studies measured access to hearing-specific services; 22%
      vision-specific; 31% physical impairment-specific; and 44% measured access to
      mental impairment-specific services. A further 35% measured access to services
      for any disability. A diverse range of measures of disability and access were
      used across studies making comparability difficult. However, there was some
      evidence that access to rehabilitation is low among people with disabilities. No
      clear patterns were seen in access by equity measures such as age, locality,
      socioeconomic status, or country income group due to the limited number of
      studies measuring these indicators, and the range of measures used. Access to
      rehabilitation services was highly variable and poorly measured within the
      studies in the review, but generally shown to be low. Far better metrics are
      needed, including through clinical assessment, before we have a true appreciation
      of the population level need for and coverage of these services.

PMID- 30279361
TI  - Effects of 1-Methyltryptophan on Immune Responses and the Kynurenine Pathway
      after Lipopolysaccharide Challenge in Pigs.
AB  - An enhanced indoleamine 2,3-dioxygenase 1 (IDO1) activity is associated with an
      increased mortality risk in sepsis patients. Thus, the preventive inhibition of
      IDO1 activity may be a promising strategy to attenuate the severity of septic
      shock. 1-methyltryptophan (1-MT) is currently in the interest of research due to
      its potential inhibitory effects on IDO1 and immunomodulatory properties. The
      present study aims to investigate the protective and immunomodulatory effects of
      1-methyltryptophan against endotoxin-induced shock in a porcine in vivo model.
      Effects of 1-MT were determined on lipopolysaccharide (LPS)-induced tryptophan
      (TRP) degradation, immune response and sickness behaviour. 1-MT increased TRP and
      its metabolite kynurenic acid (KYNA) in plasma and tissues, suppressed the LPS
      induced maturation of neutrophils and increased inactivity of the animals. 1-MT
      did not inhibit the LPS-induced degradation of TRP to kynurenine (KYN)-a marker
      for IDO1 activity-although the increase in KYNA indicates that degradation to one
      branch of the KYN pathway is facilitated. In conclusion, our findings provide no
      evidence for IDO1 inhibition but reveal the side effects of 1-MT that may result
      from the proven interference of KYNA and 1-MT with aryl hydrocarbon receptor
      signalling. These effects should be considered for therapeutic applications of 1
      MT.

PMID- 30279360
TI  - Towards a Food-Based Intervention to Increase Protein Intakes in Older Adults:
      Challenges to and Facilitators of Egg Consumption.
AB  - : Abstract: Background: Dietary protein intake is important for health. Eggs, as
      a protein-rich food with characteristics that appeal to older adults, may provide
      opportunities for increasing protein intake. Interventions that focus on the
      challenges or facilitators that affect a large proportion of the population will
      be of increased impact on a population-wide scale. This work aimed to investigate
      the relative importance of a number of challenges to and facilitators of egg
      consumption in a UK population-wide sample of older adults. METHODS: A cross
      sectional postal questionnaire, measuring habitual egg intake, reasons for
      eating/not eating eggs and a range of demographic and lifestyle characteristics,
      was administered by post to 1082 older adults. RESULTS: 230 questionnaires
      suitable for analysis were returned (110 females, ages 55-80+ years). Habitual
      egg intake ranged from 1-89 eggs/month, mean (standard deviation) = 18 (13)
      eggs/month. Reasons for eating/not eating eggs were reduced using Principal
      Components Analysis to 23 challenges and facilitators of egg consumption.
      Regression analyses revealed habitual egg intake to be associated with 10
      challenges and facilitators (smallest beta = 0.14, p = 0.04), and with protein
      consumption, age and Body Mass Index (smallest beta = 0.14, p = 0.03).
      DISCUSSION: Many possibilities for future intervention based on existing
      challenges or facilitators were found. Our results suggest that strategies to
      increase egg consumption in older adults should focus on: improving liking,
      tastiness and adding variety; promoting eggs as an everyday type of food;
      reducing stereotypes about who does and who does not consume eggs; and promoting
      eggs for people who have noticed the effects of ageing on their food intake.
      Strategies that highlight value-for-money may be counterproductive. Future work
      evaluating the value of these strategies for improving protein intake in this age
      group would be of value.

PMID- 30279362
TI  - Soil Contamination by a Lead Smelter in Brazil in the View of the Local
      Residents.
AB  - A primary lead smelter operated in Santo Amaro City in Brazil from 1960 to 1993,
      leaving approximately 500,000 tons of industrial dross containing 2-3% of lead
      and other toxic elements that contaminated the industry grounds and the urban
      environment. This study aimed to present the local residents' perception towards
      soil contamination by the smelter. In a cross-sectional study, 208 residents from
      randomly selected households were interviewed about dross hazards and proposals
      for its management. A city map depicts the distribution and concentration of
      lead, cadmium, arsenic, zinc, nickel, and antimony, measured in the soil of the
      39 households with visible smelter dross. Only one site complies with the soil
      quality reference values; 27 (69.2%) call for preventive measures, and 11 (28.2%)
      require intervention. The smelter dross continues widely spread over the city.
      Thirty (76.9%) out of the 39 residents were able to recognize the smelter dross
      on household surroundings. However, this ability was not associated with the
      concentrations of toxic elements in the soil of their residences and
      surroundings. The smelter and the local Prefecture were most frequently held
      liable for taking soil cleanup actions. The most frequently (38.0%) cited
      solution for managing the dross found in the households was "to provide the
      residents with information about health risks related to the dross".

PMID- 30279364
TI  - Development and Validation of a Recipe Method for Doughs.
AB  - Recipes have a great impact on consumers' behavior in the kitchen; building a
      recipe requires the understanding of the potential user. The objective of this
      study was to develop and evaluate different recipe styles for the preparation of
      doughs by understanding people's descriptions of these. Two qualitative studies
      were performed (43 wheat and 50 corn dough preparers). During interviews,
      participants described the preparation process of the doughs using the Think
      Aloud technique. Finished doughs were described as not sticky, soft, and pliable.
      Based on these descriptions, five recipes were created: not detailed, detailed,
      very detailed, paragraph-form, and 'with images'. Recipes were validated in two
      online surveys (total n = 600), where respondents evaluated the easiness,
      likeability, likelihood of using, helpfulness, and amount of information.
      Respondents considered the recipe with images as easier and more helpful. The
      very detailed recipe was considered more difficult, less helpful, and was liked
      less than the other recipes. Understanding and identifying the terms and
      techniques people use is a good way to communicate how to prepare a food product
      and can be used to develop and improve recipes. However, the format in which the
      recipe is presented is an important factor considered by users when following
      recipes.

PMID- 30279363
TI  - Gap Junction Intercellular Communication Positively Regulates Cisplatin Toxicity
      by Inducing DNA Damage through Bystander Signaling.
AB  - The radiation-induced bystander effect (RIBE) can increase cellular toxicity in a
      gap junction dependent manner in unirradiated bystander cells. Recent reports
      have suggested that cisplatin toxicity can also be mediated by functional gap
      junction intercellular communication (GJIC). In this study using lung and ovarian
      cancer cell lines, we showed that cisplatin cytotoxicity is mediated by cellular
      density. This effect is ablated when GJA1 or Connexin 43 (Cx43) is targeted, a
      gap junction gene and protein, respectively, leading to cisplatin resistance but
      only at high or gap junction forming density. We also observed that the cisplatin
      mediated bystander effect was elicited as DNA Double Strand Breaks (DSBs) with
      positive H2AX Ser139 phosphorylation (gammaH2AX) formation, an indicator of DNA
      DSBs. These DSBs are not observed when gap junction formation is prevented. We
      next showed that cisplatin is not the "death" signal traversing the gap junctions
      by utilizing the cisplatin-GG intrastrand adduct specific antibody. Finally, we
      also showed that cells deficient in the structure-specific DNA endonuclease ERCC1
      ERCC4 (ERCC1-XPF), an important mediator of cisplatin resistance, further
      sensitized when treated with cisplatin in the presence of gap junction forming
      density. Taken together, these results demonstrate the positive effect of GJIC on
      increasing cisplatin cytotoxicity.

PMID- 30279365
TI  - Exogenous C8-Ceramide Induces Apoptosis by Overproduction of ROS and the Switch
      of Superoxide Dismutases SOD1 to SOD2 in Human Lung Cancer Cells.
AB  - Ceramides, abundant sphingolipids on the cell membrane, can act as signaling
      molecules to regulate cellular functions including cell viability. Exogenous
      ceramide has been shown to exert potent anti-proliferative effects against cancer
      cells, but little is known about how it affects reactive oxygen species (ROS) in
      lung cancer cells. In this study, we investigated the effect of N-octanoyl-D
      erythro-sphingosine (C8-ceramide) on human non-small-cell lung cancer H1299
      cells. Flow cytometry-based assays indicated that C8-ceramide increased the level
      of endogenous ROS in H1299 cells. Interestingly, the ratio of superoxide
      dismutases (SODs) SOD1 and SOD2 seem to be regulated by C8-ceramide treatment.
      Furthermore, the accumulation of cell cycle G1 phase and apoptotic populations in
      C8-ceramide-treated H1299 cells was observed. The results of the Western blot
      showed that C8-ceramide causes a dramatically increased protein level of cyclin
      D1, a critical regulator of cell cycle G1/S transition. These results suggest
      that C8-ceramide acts as a potent chemotherapeutic agent and may increase the
      endogenous ROS level by regulating the switch of SOD1 and SOD2, causing the anti
      proliferation, and consequently triggering the apoptosis of NSCLC H1299 cells.
      Accordingly, our works may give a promising strategy for lung cancer treatment in
      the future.

PMID- 30279367
TI  - Interference of Biodegradable Plastics in the Polypropylene Recycling Process.
AB  - Recycling polymers is common due to the need to reduce the environmental impact
      of these materials. Polypropylene (PP) is one of the polymers called 'commodities
      polymers' and it is commonly used in a wide variety of short-term applications
      such as food packaging and agricultural products. That is why a large amount of
      PP residues that can be recycled are generated every year. However, the current
      increasing introduction of biodegradable polymers in the food packaging industry
      can negatively affect the properties of recycled PP if those kinds of plastics
      are disposed with traditional plastics. For this reason, the influence that
      generates small amounts of biodegradable polymers such as polylactic acid (PLA),
      polyhydroxybutyrate (PHB) and thermoplastic starch (TPS) in the recycled PP were
      analyzed in this work. Thus, recycled PP was blended with biodegradables polymers
      by melt extrusion followed by injection moulding process to simulate the
      industrial conditions. Then, the obtained materials were evaluated by studding
      the changes on the thermal and mechanical performance. The results revealed that
      the vicat softening temperature is negatively affected by the presence of
      biodegradable polymers in recycled PP. Meanwhile, the melt flow index was
      negatively affected for PLA and PHB added blends. The mechanical properties were
      affected when more than 5 wt.% of biodegradable polymers were present. Moreover,
      structural changes were detected when biodegradable polymers were added to the
      recycled PP by means of FTIR, because of the characteristic bands of the carbonyl
      group (between the band 1700-1800 cm-1) appeared due to the presence of PLA, PHB
      or TPS. Thus, low amounts (lower than 5 wt.%) of biodegradable polymers can be
      introduced in the recycled PP process without affecting the overall performance
      of the final material intended for several applications, such as food packaging,
      agricultural films for farming and crop protection.

PMID- 30279366
TI  - 2D Material Science: Defect Engineering by Particle Irradiation.
AB  - Two-dimensional (2D) materials are at the heart of many novel devices due to
      their unique and often superior properties. For simplicity, 2D materials are
      often assumed to exist in their text-book form, i.e., as an ideal solid with no
      imperfections. However, defects are ubiquitous in macroscopic samples and play an
      important - if not imperative - role for the performance of any device. Thus,
      many independent studies have targeted the artificial introduction of defects
      into 2D materials by particle irradiation. In our view it would be beneficial to
      develop general defect engineering strategies for 2D materials based on a
      thorough understanding of the defect creation mechanisms, which may significantly
      vary from the ones relevant for 3D materials. This paper reviews the state-of-the
      art in defect engineering of 2D materials by electron and ion irradiation with a
      clear focus on defect creation on the atomic scale and by individual impacts.
      Whenever possible we compile reported experimental data alongside corresponding
      theoretical studies. We show that, on the one hand, defect engineering by
      particle irradiation covers a wide range of defect types that can be fabricated
      with great precision in the most commonly investigated 2D materials. On the other
      hand, gaining a complete understanding still remains a challenge, that can be met
      by combining advanced theoretical methods and improved experimental set-ups, both
      of which only now begin to emerge. In conjunction with novel 2D materials, this
      challenge promises attractive future opportunities for researchers in this field.

PMID- 30279368
TI  - Establishing the Phenolic Composition of Olea europaea L. Leaves from Cultivars
      Grown in Morocco as a Crucial Step Towards Their Subsequent Exploitation.
AB  - In Morocco, the recovery of olive agro-industrial by-products as potential
      sources of high-added value substances has been underestimated so far. A
      comprehensive quantitative characterization of olive leaves' bioactive compounds
      is crucial for any attempt to change this situation and to implement the
      valorization concept in emerging countries. Thus, the phenolic fraction of olive
      leaves of 11 varieties ('Arbequina', 'Hojiblanca', 'Frantoio', 'Koroneiki',
      'Lechin', 'Lucque', 'Manzanilla', 'Picholine de Languedoc', 'Picholine
      Marocaine', 'Picual' and 'Verdal'), cultivated in the Moroccan Meknes region, was
      investigated. Thirty eight phenolic or related compounds (including 16
      secoiridoids, nine flavonoids in their aglycone form, seven flavonoids in
      glycosylated form, four simple phenols, one phenolic acid and one lignan) were
      determined in a total of 55 samples by using ultrasonic-assisted extraction and
      liquid chromatography coupled to electrospray ionization-ion trap mass
      spectrometry (LC-ESI-IT MS). Very remarkable quantitative differences were
      observed among the profiles of the studied cultivars. 'Picholine Marocaine'
      variety exhibited the highest total phenolic content (around 44 g/kg dry weight
      (DW)), and logically showed the highest concentration in terms of various
      individual compounds. In addition, chemometrics (principal components analysis
      (PCA) and stepwise-linear discriminant analysis (s-LDA)) were applied to the
      quantitative phenolic compound data, allowing good discrimination of the selected
      samples according to their varietal origin.

PMID- 30279369
TI  - A Population-Based Approach to Mapping Vulnerability to Diabetes.
AB  - Of the 382 million people worldwide with diabetes, and if current trends
      continue, nearly half a billion people worldwide will have diabetes by 2035. Two
      thirds of current diabetics are living in urban centers and the urban
      concentration of individuals with diabetes is on the rise. The problem is that in
      the absence of widespread clinical testing, there is no reliable way to predict
      which segments of the population are the most vulnerable to the onset of
      diabetes. Knowing who the most vulnerable are, and where they live, can guide the
      efficient allocation of prevention resources. Toward this end, we introduce the
      concept of composite vulnerability, which includes both group and individual
      level attributes, and we provide a demonstration of its application to a large
      urban setting. The components of composite vulnerability are estimated using a
      novel, population-based, procedure that relies on sample survey data and
      nonparametric statistical techniques. First, cluster analysis identified three
      multivariate profiles of adult residents with type 2 diabetes, based on 35
      socioeconomic indicators. Second, the undiagnosed population was screened for
      vulnerability based on their resemblance or fit to these multivariate profiles.
      Geographic neighborhoods with high concentrations of "vulnerables" could then be
      identified. In parallel, recursive partitioning found the best predictors of type
      2 diabetes in this urban population, combined them with indicators of
      disadvantage, and applied them to residents in the selected neighborhoods to
      establish relative levels of composite vulnerability. Neighborhoods with high
      concentrations of residents manifesting composite vulnerability can be easily
      identified for targeting community-based prevention measures.

PMID- 30279370
TI  - A Hybrid Textile Electrode for Electrocardiogram (ECG) Measurement and Motion
      Tracking.
AB  - Wearable sensors have great potential uses in personal health monitoring systems,
      in which textile-based electrodes are particularly useful because they are
      comfortable to wear and are skin and environmentally friendly. In this paper, a
      hybrid textile electrode for electrocardiogram (ECG) measurement and motion
      tracking was introduced. The hybrid textile electrode consists of two parts: A
      textile electrode for ECG monitoring, and a motion sensor for patient activity
      tracking. In designing the textile electrodes, their performance in ECG
      measurement was investigated. Two main influencing factors on the skin-electrode
      impedance of the electrodes were found: Textile material properties, and
      electrode sizes. The optimum textile electrode was silver plated, made of a high
      stitch density weft knitted conductive fabric and its size was 20 mm * 40 mm. A
      flexible motion sensor circuit was designed and integrated within the textile
      electrode. Systematic measurements were performed, and results have shown that
      the hybrid textile electrode is capable of recording ECG and motion signals
      synchronously, and is suitable for ambulatory ECG measurement and motion tracking
      applications.

PMID- 30279371
TI  - Effect of Oxygen Partial Pressure on the Phase Stability of Copper-Iron
      Delafossites at Elevated Temperatures.
AB  - Oxide-based materials are promising candidates for use in high temperature
      thermoelectric generators. While their thermoelectric performance is inferior to
      commonly used thermoelectrics, oxides are environmentally friendly and cost
      effective. In this study, Cu-based delafossites (CuFeO2), a material class with
      promising thermoelectric properties at high temperatures, were investigated. This
      work focuses on the phase stability of CuFeO2 with respect to the temperature and
      the oxygen partial pressure. For this reason, classical material characterization
      methods, such as scanning electron microscopy, energy dispersive X-ray
      spectroscopy, and X-ray diffraction, were combined in order to elucidate the
      phase composition of delafossites at 900  degrees C at various oxygen partial
      pressures. The experimentally obtained results are supported by the theoretical
      calculation of the Ellingham diagram of the copper-oxygen system. In addition,
      hot-stage X-ray diffraction and long-term annealing tests of CuFeO2 were
      performed in order to obtain a holistic review of the phase stability of
      delafossites at high temperatures and varying oxygen partial pressure. The
      results support the thermoelectric measurements in previous publications and
      provide a process window for the use of CuFeO2 in thermoelectric generators.

PMID- 30279372
TI  - Assay Challenges for Emerging Infectious Diseases: The Zika Experience.
AB  - From the perspective of vaccine development, it is imperative to accurately
      diagnose target infections in order to exclude subjects with prior exposure from
      evaluations of vaccine effectiveness, to track incident infection during the
      course of a clinical trial and to differentiate immune reactions due to natural
      infections from responses that are vaccine related. When vaccine development is
      accelerated to a rapid pace in response to emerging infectious disease threats,
      the challenges to develop such diagnostic tools is even greater. This was
      observed through the recent expansion of Zika virus infections into the Western
      Hemisphere in 2014-2017. When initial Zika vaccine clinical trials were being
      designed and launched in response to the outbreak, there were no standardized
      sets of viral and immunological assays, and no approved diagnostic tests for Zika
      virus infection. The diagnosis of Zika virus infection is still an area of active
      research and development on many fronts. Here we review emerging infectious
      disease vaccine clinical assay development and trial execution with a special
      focus on the state of Zika virus clinical assays and diagnostics.

PMID- 30279373
TI  - Many-Objective Automated Optimization of a Four-Band Antenna for Multiband
      Wireless Sensor Networks.
AB  - This paper describes a new design and an optimization framework for a four-band
      antenna to be used in wireless sensor networks. The antenna is designed to
      operate effectively in two open frequency bands (ISM-Industrial, Scientific,
      Medical), 2.4 GHz and 5.8 GHz, as well as in two bands allocated for the fifth
      generation (5G) cellular networks, 0.7 GHz and 3.5 GHz. Our initial design was
      developed using the trial and error approach, modifying a circular disc monopole
      antenna widely used in ultra wideband (UWB) systems. This initial design covered
      the three upper bands, but impedance matching within the 700 MHz band was
      unsatisfactory. The antenna performance was then improved significantly using an
      optimization algorithm that applies a bi-objective fully-Paretian approach to its
      nine-parameter geometry. The optimization criteria were impedance matching and
      radiation efficiency. The final design exhibits good impedance matching in all
      four desired bands with the Voltage Standing Wave Ratio (VSWR) value below 2 and
      radiation efficiency of 88%. The simulated antenna performance was verified
      experimentally.

PMID- 30279374
TI  - Towards an Automated Unsupervised Mobility Assessment for Older People Based on
      Inertial TUG Measurements.
AB  - One of the most common assessments for the mobility of older people is the Timed
      Up and Go test (TUG). Due to its sensitivity regarding the indication of
      Parkinson's disease (PD) or increased fall risk in elderly people, this
      assessment test becomes increasingly relevant, should be automated and should
      become applicable for unsupervised self-assessments to enable regular
      examinations of the functional status. With Inertial Measurement Units (IMU)
      being well suited for automated analyses, we evaluate an IMU-based analysis
      system, which automatically detects the TUG execution via machine learning and
      calculates the test duration. as well as the duration of its single components.
      The complete TUG was classified with an accuracy of 96% via a rule-based model in
      a study with 157 participants aged over 70 years. A comparison between the TUG
      durations determined by IMU and criterion standard measurements (stopwatch and
      automated/ambient TUG (aTUG) system) showed significant correlations of 0.97 and
      0.99, respectively. The classification of the instrumented TUG (iTUG)-components
      achieved accuracies over 96%, as well. Additionally, the system's suitability for
      self-assessments was investigated within a semi-unsupervised situation where a
      similar movement sequence to the TUG was executed. This preliminary analysis
      confirmed that the self-selected speed correlates moderately with the speed in
      the test situation, but differed significantly from each other.

PMID- 30279376
TI  - Wide-Angle, Ultra-Wideband ISAR Imaging of Vehicles and Drones.
AB  - In-situ, wide-angle, and ultra-wideband inverse synthetic aperture radar (ISAR)
      imaging of vehicles and drones is demonstrated using a portable ultra-wideband
      radar. In order to form well-focused ISAR images, motion compensation is
      performed before applying the k-space imaging algorithm. While the same basic
      motion compensation methodology is applied to both types of targets, a more
      complex motion model is needed to better capture the flight path of the drone.
      The resulting ISAR images clearly show the geometrical outline of the targets and
      highlight locations of prominent backscattering. The ISAR images are also
      assessed against images generated through instrumented targets or laboratory
      measurements, and the image quality is shown to be comparable.

PMID- 30279375
TI  - Genome-Wide Association Study Reveals Novel Genomic Regions for Grain Yield and
      Yield-Related Traits in Drought-Stressed Synthetic Hexaploid Wheat.
AB  - Synthetic hexaploid wheat (SHW; 2n = 6x = 42, AABBDD, Triticum aestivum L.) is
      produced from an interspecific cross between durum wheat (2n = 4x = 28, AABB, T.
      turgidum L.) and goat grass (2n = 2x = 14, DD, Aegilops tauschii Coss.) and is
      reported to have significant novel alleles-controlling biotic and abiotic
      stresses resistance. A genome-wide association study (GWAS) was conducted to
      unravel these loci [marker-trait associations (MTAs)] using 35,648 genotyping-by
      sequencing-derived single nucleotide polymorphisms in 123 SHWs. We identified 90
      novel MTAs (45, 11, and 34 on the A, B, and D genomes, respectively) and
      haplotype blocks associated with grain yield and yield-related traits including
      root traits under drought stress. The phenotypic variance explained by the MTAs
      ranged from 1.1% to 32.3%. Most of the MTAs (120 out of 194) identified were
      found in genes, and of these 45 MTAs were in genes annotated as having a
      potential role in drought stress. This result provides further evidence for the
      reliability of MTAs identified. The large number of MTAs (53) identified
      especially on the D-genome demonstrate the potential of SHWs for elucidating the
      genetic architecture of complex traits and provide an opportunity for further
      improvement of wheat under rapidly changing climatic conditions.

PMID- 30279377
TI  - Early Responses to Severe Drought Stress in the Arabidopsis thaliana Cell
      Suspension Culture Proteome.
AB  - Abiotic stresses are considered the most deleterious factor affecting growth and
      development of plants worldwide. Such stresses are largely unavoidable and
      trigger adaptive responses affecting different cellular processes and target
      different compartments. Shotgun proteomic and mass spectrometry-based approaches
      offer an opportunity to elucidate the response of the proteome to abiotic
      stresses. In this study, the severe drought or water-deficit response in
      Arabidopsis thaliana was mimicked by treating cell suspension callus with 40%
      polyethylene glycol for 10 and 30 min. Resulting data demonstrated that 310
      proteins were differentially expressed in response to this treatment with a
      strict +/-2.0-fold change. Over-representation was observed in the gene ontology
      categories of 'ribosome' and its related functions as well as 'oxidative
      phosphorylation', indicating both structural and functional drought responses at
      the cellular level. Proteins in the category 'endocytosis' also show significant
      enrichment and this is consistent with increased active transport and recycling
      of membrane proteins in response to abiotic stress. This is supported by the
      particularly pronounced enrichment in proteins of the endosomal sorting complexes
      that are required for membrane remodelling. Taken together, the findings point to
      rapid and complex physiological and structural changes essential for survival in
      response to sudden severe drought stress.

PMID- 30279378
TI  - Coencapsulation of Polyphenols and Anthocyanins from Blueberry Pomace by Double
      Emulsion Stabilized by Whey Proteins: Effect of Homogenization Parameters.
AB  - Blueberry pomace is a rich source of high-value bioactive polyphenols with
      presumed health benefits. Their incorporation into functional foods and health
      related products benefits from coencapsulation and protection of polyphenol-rich
      extracts in suitable carriers. This study aimed to create a water-in-oil-in-water
      (W1/O/W2) double emulsion system suitable for the coencapsulation of total
      phenolics (TP) and anthocyanins (TA) from a polyphenol-rich extract of blueberry
      pomace (W1). The effect of critical physical parameters for preparing stable
      double emulsions, namely homogenization pressure, stirring speed and time, was
      investigated by measuring the hydrodynamic diameter, size dispersity and zeta
      potential of the oil droplets, and the encapsulation efficiency of TP and TA. The
      oil droplets were negatively charged (negative zeta potential values), which was
      related to the pH and composition of W2 (whey protein isolate solution) and
      suggests stabilization by the charged whey proteins. Increasing W1/O/W2
      microfluidization pressure from 50 to 200 MPa or homogenization speed from 6000
      to 12,000 rpm significantly increased droplet diameter and zeta potential and
      decreased TA and TP encapsulation efficiency. Increasing W1/O/W2 homogenization
      time from 15 to 20 min also increased droplet diameter and zeta potential and
      lowered TA encapsulation efficiency, while TP encapsulation did not vary
      significantly. In contrast, increasing W1/O homogenization time from 5 to 10 min
      at 10,000 rpm markedly increased TA encapsulation efficiency and reduced droplet
      diameter and zeta potential. High coencapsulation rates of blueberry polyphenols
      and anthocyanins around 80% or greater were achieved when the oil droplets were
      relatively small (mean diameter < 400 nm), with low dispersity (<0.25) and a high
      negative surface charge (-40 mV or less). These characteristics were obtained by
      homogenizing for 10 min at 10,000 rpm (W1/O), then 6000 rpm for 15 min, followed
      by microfluidization at 50 MPa.

PMID- 30279379
TI  - SRSF3, a Splicer of the PKM Gene, Regulates Cell Growth and Maintenance of Cancer
      Specific Energy Metabolism in Colon Cancer Cells.
AB  - Serine and arginine rich splicing factor 3 (SRSF3), an SR-rich family protein,
      has an oncogenic function in various kinds of cancer. However, the detailed
      mechanism of the function had not been previously clarified. Here, we showed that
      the SRSF3 splicer regulated the expression profile of the pyruvate kinase, which
      is one of the rate-limiting enzymes in glycolysis. Most cancer cells express
      pyruvate kinase muscle 2 (PKM2) dominantly to maintain a glycolysis-dominant
      energy metabolism. Overexpression of SRSF3, as well as that of another splicer,
      polypyrimidine tract binding protein 1 (PTBP1) and heterogeneous nuclear
      ribonucleoprotein A1 (hnRNPA1), in clinical cancer samples supported the notion
      that these proteins decreased the Pyruvate kinase muscle 1 (PKM1)/PKM2 ratio,
      which positively contributed to a glycolysis-dominant metabolism. The silencing
      of SRSF3 in human colon cancer cells induced a marked growth inhibition in both
      in vitro and in vivo experiments and caused an increase in the PKM1/PKM2 ratio,
      thus resulting in a metabolic shift from glycolysis to oxidative phosphorylation.
      At the same time, the silenced cells were induced to undergo autophagy. SRSF3
      contributed to PKM mRNA splicing by co-operating with PTBP1 and hnRNPA1, which
      was validated by the results of RNP immunoprecipitation (RIP) and
      immunoprecipitation (IP) experiments. These findings altogether indicated that
      SRSF3 as a PKM splicer played a positive role in cancer-specific energy
      metabolism.

PMID- 30279381
TI  - Analysis of the Bearing Capacity of Helical Pile with Hexagonal Joints.
AB  - This study aims to improve shafts with hexagonal joints so that they will not
      require welding or bolts in static load tests. In order to evaluate the bearing
      capacity of helical piles, two sites were selected to conduct pile installation
      for the field test and the pile load test. For the pile load test, a static pile
      load test and a dynamic pile load test were carried out, and torque was measured
      during pile installation in a field test to compare and analyze the expected
      bearing capacity and thus assess the feasibility of the method for estimating the
      bearing capacity. The field pile load test revealed that the bearing capacity of
      the gravity grout pile was the same or greater than 600 kN in the static pile
      load test in accordance with the AC 358 code. The non-grout pile showed a bearing
      capacity that was the same or smaller than 600 kN, suggesting that gravity
      grouting is required. Moreover, the field pile load test was used to establish
      the bearing capacity equation considering the torque in the pile installation,
      and a small number of samples were used to establish the equation, which can be
      used as basic data.

PMID- 30279382
TI  - Probing the Action of Permeation Enhancers Sodium Cholate and N-dodecyl-beta-D
      maltoside in a Porcine Jejunal Mucosal Explant System.
AB  - The small intestinal epithelium constitutes a major permeability barrier for the
      oral administration of therapeutic drugs with poor bioavailability, and
      permeation enhancers (PEs) are required to increase the paracellular and/or
      transcellular uptake of such drugs. Many PEs act as surfactants by perturbing
      cell membrane integrity and causing permeabilization by leakage or endocytosis.
      The aim of the present work was to study the action of sodium cholate (NaC) and N
      dodecyl-beta-D-maltoside (DDM), using a small intestinal mucosal explant system.
      At 2 mM, both NaC and DDM caused leakage into the enterocyte cytosol of the
      fluorescent probe Lucifer Yellow, but they also blocked the constitutive
      endocytotic pathway from the brush border. In addition, an increased paracellular
      passage of 3-kDa Texas Red Dextran into the lamina propria was observed. By
      electron microscopy, both PEs disrupted the hexagonal organization of microvilli
      of the brush border and led to the apical extrusion of vesicle-like and amorphous
      cell debris to the lumen. In conclusion, NaC and DDM acted in a multimodal way to
      increase the permeability of the jejunal epithelium both by paracellular and
      transcellular mechanisms. However, endocytosis, commonly thought to be an uptake
      mechanism that may be stimulated by PEs, was not involved in the transcellular
      process.

PMID- 30279380
TI  - Biodegradation of Some Organic Materials in Soils and Soil Constructions:
      Experiments, Modeling and Prevention.
AB  - The decomposition of natural and synthetic polymeric materials (peat, humates,
      biochar, strongly swelling hydrogels and other soil conditioners) in a
      biologically and chemically active soil environment inevitably leads to a reduced
      ability to improve the structure, water-retention, absorptive capacity and
      fertility of artificial soil constructions in urbanized ecosystems and agro
      landscapes (constructozems). Quantitative assessment of the biodegradation
      process using field and laboratory incubation experiments, as well as
      mathematical modeling, showed the possibility of significant (up to 30-50% per
      year) losses of organic matter of constructozems and a corresponding
      deterioration of soil quality. Incubation experiments that track the carbon
      dioxide emission rates of polymeric materials under given thermodynamic
      conditions allow for the estimation of decomposition rates in addition to an
      exploration on the dependence of such rates on additions of microbial inhibitors.
      The use of nomographs provide an opportunity to optimize long-term amendment
      performance in soil constructions by identifying the most favorable depths to
      apply amendments to ensure stable functioning during desired in-service timelines
      in the built environment. The results of the study are useful for geo-engineers
      and landscaping practitioners.

PMID- 30279383
TI  - Self-Adaptive Spectrum Analysis Based Bearing Fault Diagnosis.
AB  - Bearings are critical parts of rotating machines, making bearing fault diagnosis
      based on signals a research hotspot through the ages. In real application
      scenarios, bearing signals are normally non-linear and unstable, and thus
      difficult to analyze in the time or frequency domain only. Meanwhile, fault
      feature vectors extracted conventionally with fixed dimensions may cause
      insufficiency or redundancy of diagnostic information and result in poor
      diagnostic performance. In this paper, Self-adaptive Spectrum Analysis (SSA) and
      a SSA-based diagnosis framework are proposed to solve these problems. Firstly,
      signals are decomposed into components with better analyzability. Then, SSA is
      developed to extract fault features adaptively and construct non-fixed dimension
      feature vectors. Finally, Support Vector Machine (SVM) is applied to classify
      different fault features. Data collected under different working conditions are
      selected for experiments. Results show that the diagnosis method based on the
      proposed diagnostic framework has better performance. In conclusion, combined
      with signal decomposition methods, the SSA method proposed in this paper achieves
      higher reliability and robustness than other tested feature extraction methods.
      Simultaneously, the diagnosis methods based on SSA achieve higher accuracy and
      stability under different working conditions with different sample division
      schemes.

PMID- 30279385
TI  - Physical Activity and Gastric Cancer Risk in Patients with and without
      Helicobacter pylori Infection in A Korean Population: A Hospital-Based Case
      Control Study.
AB  - Although physical activity (PA) is beneficial for prolonging lifespan, evidence
      for the protective role of PA against the development of gastric cancer (GC) is
      not yet well established. This study assessed the association between PA and GC
      risk in patients with and without Helicobacter pylori (H. pylori) infection in a
      Korean population. In total, 415 GC patients and 830 controls were enrolled at
      the National Cancer Center, Korea. The International Physical Activity
      Questionnaire-Short Form was used to collect PA data. The odds ratios (ORs) and
      95% confidence intervals (CIs) were estimated using unconditional logistic
      regression models. In the H. pylori-positive group, subjects who engaged in
      regular exercise showed a significantly reduced risk of GC in the entire
      population (OR = 0.52, 95% CI = 0.38-0.70) and in females (OR = 0.60, 95% CI =
      0.21-0.64). Subjects who engaged in a high level of total PA showed a
      significantly reduced risk of GC relative to subjects in the lowest tertile in
      the fully adjusted model (OR = 0.46, 95% CI = 0.32-0.65, p-trend < 0.001). There
      was an inverse association between PA and GC risk in the entire population, and
      in the H. pylori-positive subgroup. Our data indicate the need for the promotion
      of all domains of PA, especially for Korean populations.

PMID- 30279384
TI  - A Review on the Gluten-Free Diet: Technological and Nutritional Challenges.
AB  - Consumers, food manufacturers and health professionals are uniquely influenced by
      the growing popularity of the gluten-free diet. Consumer expectations have urged
      the food industry to continuously adjust and improve the formulations and
      processing techniques used in gluten-free product manufacturing. Health experts
      have been interested in the nutritional adequacy of the diet, as well as its
      effectiveness in managing gluten-related disorders and other conditions. In this
      review, we aim to provide a clear picture of the current motivations behind the
      use of gluten-free diets, as well as the technological and nutritional challenges
      of the diet as a whole. Alternative starches and flours, hydrocolloids, and fiber
      sources were found to play a complex role in mimicking the functional and sensory
      effects of gluten in gluten-free products. However, the quality of gluten-free
      alternatives is often still inferior to the gluten-containing products.
      Furthermore, the gluten-free diet has demonstrated benefits in managing some
      gluten-related disorders, though nutritional imbalances have been reported. As
      there is limited evidence supporting the use of the gluten-free diet beyond its
      role in managing gluten-related disorders, consumers are urged to be mindful of
      the sensorial limitations and nutritional inadequacies of the diet despite
      ongoing strategies to improve them.

PMID- 30279386
TI  - Preparation of a Defined Gluten Hydrolysate for Diagnosis and Clinical
      Investigations of Wheat Hypersensitivities.
AB  - Gluten is the trigger for celiac disease (CD), non-celiac gluten/wheat
      sensitivity (NCGS), and wheat allergy. An oral food challenge is often needed for
      diagnosis, but there are no standardized gluten challenge materials with known
      composition available. To fill this gap, two materials, commercially available
      gluten and a food-grade gluten hydrolysate (pepgluten), were extensively
      characterized. Pepgluten was prepared from gluten by incubation with a pepsin
      dietary supplement and acetic acid at 37  degrees C for 120 min. The components
      of pepgluten were crude protein (707 mg/g), starch (104 mg/g), water (59 mg/g),
      fat (47 mg/g), dietary fiber (41 mg/g) and ash (11 mg/g). The protein/peptide
      fraction of pepgluten (1 g) contained equivalents derived from 369 mg gliadins
      and 196 mg glutenins, resulting in 565 mg total gluten equivalents, 25 mg
      albumins/globulins, 22 mg alpha-amylase/trypsin inhibitors and 48 mg pepsin
      capsule proteins. The slightly acidic, dough-like smell and bitter taste of
      pepgluten could be completely camouflaged in multivitamin juice with bitter
      lemon, grapefruit juice, or vegetable and fruit smoothies. Thus, pepgluten met
      the criteria for placebo-controlled challenges (active and placebo materials are
      identical regarding appearance, taste, smell, and texture) and is appropriate as
      a standard preparation for the oral food challenge and clinical investigations to
      study wheat hypersensitivities.

PMID- 30279387
TI  - Integration of a 2D Touch Sensor with an Electroluminescent Display by Using a
      Screen-Printing Technology on Textile Substrate.
AB  - Many types of solutions have been studied and developed in order to give the user
      feedback when using touchpads, buttons, or keyboards in textile industry. Their
      application on textiles could allow a wide range of applications in the field of
      medicine, sports or the automotive industry. In this work, we introduce a novel
      solution that combines a 2D touchpad with an electroluminescent display (ELD).
      This approach physically has two circuits over a flexible textile substrate using
      the screen-printing technique for wearable electronics applications. Screen
      printing technology is widely used in the textile industry and does not require
      heavy investments. For the proposed solution, different layer structures are
      presented, considering several fabric materials and inks, to obtain the best
      results.

PMID- 30279388
TI  - Melaleuca styphelioides Sm. Polyphenols Modulate Interferon Gamma/Histamine
      Induced Inflammation in Human NCTC 2544 Keratinocytes.
AB  - Melaleuca styphelioides, known as the prickly-leaf tea tree, contains a variety
      of bioactive compounds. The purposes of this study were to characterize the
      polyphenols extracted from Melaleuca styphelioides leaves and assess their
      potential antioxidant and anti-inflammatory effects. The polyphenol extracts were
      prepared by maceration with solvents of increasing polarity. The LC/MS-MS
      technique was used to identify and quantify the phenolic compounds. An assessment
      of the radical scavenging activity of all extracts was performed using 2,2
      diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6
      sulphonate) (ABTS+), and ferric reducing antioxidant power (FRAP) assays. The
      anti-inflammatory activity was determined on interferon gamma (IFN
      gamma)/histamine (H)-stimulated human NCTC 2544 keratinocytes by Western blot and
      RT-PCR. Compared to other solvents, methanolic extract presented the highest
      level of phenolic contents. The most frequent phenolic compounds were quercetin,
      followed by gallic acid and ellagic acid. DPPH, ABTS+, and FRAP assays showed
      that methanolic extract exhibits strong concentration-dependent antioxidant
      activity. IFN-gamma/H treatment of human NCTC 2544 keratinocytes induced the
      secretion of high levels of the pro-inflammatory mediator inter-cellular adhesion
      molecule-1 (ICAM-1), nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and
      nuclear factor kappa B (NF-kappaB), which were inhibited by extract. In
      conclusion, the extract of Melaleuca styphelioides leaves is rich in flavonoids,
      and presents antioxidant and anti-inflammatory proprieties. It can be proposed as
      a useful compound to treat inflammatory skin diseases.

PMID- 30279390
TI  - Real-Time Lossless Compression Algorithm for Ultrasound Data Using BL Universal
      Code.
AB  - Software-based ultrasound imaging systems provide high flexibility that allows
      easy and fast adoption of newly developed algorithms. However, the extremely high
      data rate required for data transfer from sensors (e.g., transducers) to the
      ultrasound imaging systems is a major bottleneck in the software-based
      architecture, especially in the context of real-time imaging. To overcome this
      limitation, in this paper, we present a Binary cLuster (BL) code, which yields an
      improved compression ratio compared to the exponential Golomb code. Owing to the
      real-time encoding/decoding features without overheads, the universal code is a
      good solution to reduce the data transfer rate for software-based ultrasound
      imaging. The performance of the proposed method was evaluated using in vitro and
      in vivo data sets. It was demonstrated that the BL-beta code has a good stable
      lossless compression performance of 20%~30% while requiring no auxiliary memory
      or storage.

PMID- 30279391
TI  - Beta-Glucanemia after Coronary Artery Bypass Graft Surgery: A Case Report.
AB  - Blood salvage techniques are increasingly being used during surgical procedures
      to reduce the need for exogenous blood products. The blood recovered from the
      surgical field through aspiration or absorption by surgical sponges is reinfused
      into a patient. A 65-year old patient who underwent coronary artery bypass
      grafting using blood salvage techniques developed a fever on post-op day 3 and
      was noted to have an elevated beta-d-glucan level, a marker of systemic fungal
      infections. Ultimately, no fungal infection was identified, beta-d-glucan levels
      slowly decreased and the patient demonstrated clinical improvement. To determine
      whether blood salvage procedures led to his elevated beta-d-glucan levels, the
      surgical sponges were tested for elutable levels of beta-d-glucan. The beta-d
      glucan content of the eluents was measured using the Fungitell(r) IVD kit
      (Associates of Cape Cod, Inc.; East Falmouth, MA). The beta-d-glucan levels were
      found to be in concentrations 10,000-times greater than the limit of detection
      for human serum. While various studies have demonstrated both the
      immunomodulatory and pro-inflammatory effects of beta-d-glucan, the physiologic
      impact of such high levels of beta-d-glucan post-operatively remains unknown.
      Additionally, the persistence of detectable beta-d-glucan up to several weeks
      after surgical procedures presents a challenge for the diagnosis of invasive
      fungal infections. Further studies are needed to assess the beta-glucanemia
      related safety of surgical materials and their potential biological effects.

PMID- 30279389
TI  - Effects of Phytoremediation Treatment on Bacterial Community Structure and
      Diversity in Different Petroleum-Contaminated Soils.
AB  - Increased exploitation and use of petroleum resources is leading to increased
      risk of petroleum contamination of soil and groundwater. Although
      phytoremediation is a widely-used and cost-effective method for rehabilitating
      soils polluted by petroleum, bacterial community structure and diversity in soils
      undergoing phytoremediation is poorly understood. We investigate bacterial
      community response to phytoremediation in two distinct petroleum-contaminated
      soils (add prepared petroleum-contaminated soils) from northwest China, Weihe
      Terrace soil and silty loam from loess tableland. High-throughput sequencing
      technology was used to compare the bacterial communities in 24 different samples,
      yielding 18,670 operational taxonomic units (OTUs). The dominant bacterial
      groups, Proteobacteria (31.92%), Actinobacteria (16.67%), Acidobacteria (13.29%)
      and Bacteroidetes (6.58%), increased with increasing petroleum concentration from
      3000 mg/kg-10,000 mg/kg, while Crenarchaeota (13.58%) and Chloroflexi (4.7%)
      decreased. At the order level, RB41, Actinomycetales, Cytophagales, envOPS12,
      Rhodospirillales, MND1 and Xanthomonadales, except Nitrososphaerales, were
      dominant in Weihe Terrace soil. Bacterial community structure and diversity in
      the two soils were significantly different at similar petroleum concentrations.
      In addition, the dominant genera were affected by available nitrogen, which is
      strongly associated with the plants used for remediation. Overall, the bacterial
      community structure and diversity were markedly different in the two soils,
      depending on the species of plants used and the petroleum concentration.

PMID- 30279392
TI  - Growth, Carcass Traits, Blood Hematology, Serum Metabolites, Immunity, and
      Oxidative Indices of Growing Rabbits Fed Diets Supplemented with Red or Black
      Pepper Oils.
AB  - The present study aimed to examine the impacts of the supplementation of red or
      black pepper oils to rabbit diet as growth promoters on New Zealand white (NZW)
      rabbits. One hundred and forty weaned NZW rabbits were divided randomly into
      seven groups in a completely randomized experiment using different quantities of
      red pepper oil (RPO; 0.5, 1.0, 1.5 g/kg diet) or black pepper oil (BPO; 0.5, 1.0,
      1.5 g/kg diet), in addition to the control group. Compared to the control, values
      of live body weight (LBW) for rabbits fed either RPO or BPO enriched diets were
      greater. The concentrations of serum triglycerides and cholesterol were lower (p
      < 0.01) in the RPO- and BPO-treated groups than in the control. Immunity
      parameters and antioxidant indices were improved in treated groups in comparison
      to the control. Dietary RPO or BPO can affect some growth traits, improve
      immunity parameters and the antioxidant activity, and decrease the lipid profile
      and lipid peroxidation. The use of 0.5 g RPO/kg diet as a dietary supplement had
      a larger effect on growth parameters than the other treatment groups.

PMID- 30279393
TI  - Assessment of Long-Term Watershed Management on Reservoir Phosphorus
      Concentrations and Export Fluxes.
AB  - Source water nutrient management to prevent eutrophication requires critical
      strategies to reduce watershed phosphorus (P) loadings. Shanxi Drinking-Water
      Source Area (SDWSA) in eastern China experienced severe water quality
      deterioration before 2010, but showed considerable improvement following
      application of several watershed management actions to reduce P. This paper
      assessed the changes in total phosphorus (TP) concentrations and fluxes at the
      SDWSA outlet relative to watershed anthropogenic P sources during 2005-2016.
      Overall anthropogenic P inputs decreased by 21.5% over the study period. Domestic
      sewage, livestock, and fertilizer accounted for (mean +/- SD) 18.4 +/- 0.6%, 30.1
      +/- 1.9%, and 51.5 +/- 1.5% of total anthropogenic P inputs during 2005-2010,
      compared to 24.3 +/- 2.7%, 8.8 +/- 10.7%, and 66.9 +/- 8.0% for the 2011-2016
      period, respectively. Annual average TP concentrations in SDWSA decreased from
      0.041 +/- 0.019 mg/L in 2009 to 0.025 +/- 0.013 mg/L in 2016, a total decrease of
      38.2%. Annual P flux exported from SDWSA decreased from 0.46 +/- 0.04 kg P/(ha.a)
      in 2010 to 0.25 +/- 0.02 kg P/(ha.a) in 2016, a decrease of 44.9%. The success in
      reducing TP concentrations was mainly due to the development of domestic
      sewage/refuse collection/treatment and improved livestock management. These P
      management practices have prevented harmful algal blooms, providing for safe
      drinking water.

PMID- 30279394
TI  - Research on Formation Conditions of the Ultrafine-Grained Structure of the
      Cylindrical Parts Manufactured by Power Spinning Based on Small Strains.
AB  - Two different methods, power spinning and annealing (PSA), quenching and power
      spinning followed by annealing (QPSA), for manufacturing the cylindrical parts
      with ultrafine-grained (UFG) structure were reviewed, the dislocation density and
      microstructural evolution during the two different processes of PSA and QPSA were
      further studied. The results show that the required strains for obtaining the UFG
      structure by power spinning is only 0.92 when the initial microstructure of the
      material is in the phase of lath martensite. The dislocation density and storage
      energy are increased to 10 times that of the blank after quenching and power
      spinning and decreased to the level of the blank after recrystallization
      annealing. Microstructures with fine grain size after quenching, storage energy
      of 1.8 * 105 kJ/m3 obtained after power spinning and second phase particle with
      nano-scale precipitated during annealing are the necessary formation conditions
      for manufacturing the cylindrical parts with UFG structure based on small
      strains. Compared with the original tubular blank, the mechanical properties of
      the spun parts with UFG structure improves significantly. The tensile strength
      and hardness of the spun parts manufactured by QPSA method is 815 MPa and 305 HV,
      respectively, and the elongation is 17.5%.

PMID- 30279396
TI  - Resolving Digital Staphylococcal Osteomyelitis Using Bacteriophage-A Case Report.
AB  - Infections involving diabetic foot ulcers (DFU) are a major public health problem
      and have a substantial negative impact on patient outcomes. Osteomyelitis in an
      ulcerated foot substantially increases the difficulty of successful treatment.
      While literature suggests that osteomyelitis in selected patients can sometimes
      be treated conservatively, with no, or minimal removal of bone, we do not yet
      have clear treatment guidelines and the standard treatment failure fallback
      remains amputation. The authors report on the successful treatment, with a long
      term follow up, of a 63 YO diabetic female with distal phalangeal osteomyelitis
      using bacteriophage, a form of treatment offering the potential for improved
      outcomes in this era of escalating antibiotic resistance and the increasingly
      recognized harms associated with antibiotic therapy.

PMID- 30279395
TI  - Meat, Meat Products and Seafood as Sources of Energy and Nutrients in the Average
      Polish Diet.
AB  - The aim of this study was to identify the share of meat, meat products and
      seafood in the contribution of energy and 22 nutrients to the average Polish
      diet. Data from the nationally representative sample of Polish population (2016
      Household Budget Survey) on meat and seafood product consumption from 38,886
      households (n = 99,230) were calculated into one person per month. The analyses
      were conducted for seven food groups (e.g., red meat, poultry) and 16 products
      (e.g., beef, chicken). Approximately 18.5% of energy is delivered from the
      sources such as meat, meat products and seafood, providing a higher percentage of
      18 nutrients to the diet (e.g., 56.0% of vitamin B12, 52.3% of niacin, 44.9% of
      cholesterol, 41.5% of protein, 41.4%of vitamin D, 37.6% of monounsaturated fatty
      acids (MUFA), 37.4% of thiamin, 33.8% of zinc, 32.0% of total fats, 30.3% of
      saturated fatty acids (SFA), 29.6% of vitamin B6, 25.3% of riboflavin, 24.9% of
      phosphorus, 24.8% of iron, 22.5% of vitamin A, 21.6% of polyunsaturated fatty
      acids (PUFA) and 20.3% of sodium). For the contribution of 18 nutrients and
      energy, processed meat products were ranked first. These results should be taken
      into consideration in order to compose diets with adequate energy and nutrient
      contribution and also to analyze benefits and risk resulting from the current
      level of consumption of red and processed meat, fish and other seafood.

PMID- 30279397
TI  - Effects of Long Chain Omega-3 Polyunsaturated Fatty Acids on Brain Function in
      Mildly Hypertensive Older Adults.
AB  - Purported benefits of long chain omega-3 polyunsaturated fatty acid (LCn-3PUFA)
      for brain function may be attributable, at least in part, to improved cerebral
      perfusion. A pilot randomised controlled trial was undertaken to investigate
      effects of taking a DHA-rich fish oil supplement for 20 weeks on cerebrovascular
      function, mood and cognitive performance. Borderline hypertensives aged 40-85
      years with low habitual LCn-3PUFA intake took four capsules/day of EPAX (1600 mg
      DHA + 400 mg EPA) or placebo (corn oil). Cerebrovascular function was assessed at
      baseline and after 20 weeks in 38 completers (19 on each supplement) using
      transcranial Doppler ultrasound of blood flow in the middle cerebral artery at
      rest and whilst performing a battery of cognitive tasks (neurovascular coupling).
      The primary outcome, cerebrovascular responsiveness (CVR) to hypercapnia,
      increased 26% (p = 0.024) in women; there was no change in men. In contrast,
      neurovascular coupling increased significantly (p = 0.01 for the overall
      response) in men only; the latter correlated with an increase of EPA in
      erythrocytes (r = 0.616, p = 0.002). There was no associated improvement of mood
      or cognition in either men or women. These preliminary observations indicate that
      LCn-3PUFA supplementation has the potential to enhance blood flow in the brain in
      response to both hypercapnic and cognitive stimuli. Future studies should examine
      differential effects of EPA and DHA and take account of the gender differences in
      responsiveness to supplementation.

PMID- 30279398
TI  - Characterization of MS/MS Product Ions for the Differentiation of Structurally
      Isomeric Pesticides by High-Resolution Mass Spectrometry.
AB  - Structural isomeric pesticides are used in agriculture and may be challenging to
      differentiate for accurate identification in pesticide monitoring programs. Due
      to structural similarity, isomeric pesticides are difficult to separate
      chromatographically, and thus, their accurate identification may rely solely on
      mass spectrometric analysis (MS). In this study, we challenged the ability of
      high-resolution quadrupole-orbitrap (Q-Orbitrap) mass spectrometry to produce and
      evaluate the tandem mass spectrometry (MS/MS) product ions for the selected five
      pairs of isomeric pesticides from different classes: Pebulate and vernolate,
      methiocarb and ethiofencarb, uniconazole and cyproconazole, sebuthylazine and
      terbuthylazine, and orbencarb and thiobencarb. The use of Q-Orbitrap instrument
      with a mass error <3 ppm allowed proposed elucidation of the product ion
      structures with consideration of the ion formulae, data interpretation, and
      literature searches. Product ions unique to pebulate, vernolate, methiocarb,
      ethiofencarb, and uniconazole were observed. Elucidation of the observed MS/MS
      product ion structures was conducted, and the fragmentation pathways were
      proposed. This information is valuable to increase selectivity in MS/MS analysis
      and differentiate isomeric pesticides, and thereby reduce the rates of false
      positives in pesticide monitoring programs.

PMID- 30279400
TI  - Report from the 'One Health' 9th Tick and Tick-Borne Pathogen Conference and the
      1st Asia-Pacific Rickettsia Conference, Cairns, Australia, 27th August-1st
      September 2017.
AB  - The 9th Tick and Tick-borne Pathogen (TTP9) Conference was held in conjunction
      with the first Asia Pacific Rickettsia Conference (APRC1) in Cairns, Australia
      from 27 August until 1 September in 2017. This MDPI Veterinary Sciences Special
      Issue has been dedicated to selected veterinary science articles from the
      conference associated with the control of animal diseases in the context of ticks
      and tick-borne pathogens, including Rickettsia species. The articles presented in
      this Special Issue include novel developments for the future control of ticks and
      tick-borne diseases. This editorial describes the meeting content, the plenaries,
      the TTP awards, the MDPI Veterinary Science Special Issue articles, and serves as
      a legacy report for TTP9APRC1.

PMID- 30279401
TI  - Possible Emergence of Sequence Specific RNA Aminoacylation via Peptide
      Intermediary to Initiate Darwinian Evolution and Code Through Origin of Life.
AB  - One of the most intriguing questions in biological science is how life originated
      on Earth. A large number of hypotheses have been proposed to explain it, each
      putting an emphasis on different events leading to functional translation and
      self-sustained system. Here, we propose a set of interactions that could have
      taken place in the prebiotic environment. According to our hypothesis,
      hybridization-induced proximity of short aminoacylated RNAs led to the synthesis
      of peptides of random sequence. We postulate that among these emerged a type of
      peptide(s) capable of stimulating the interaction between specific RNAs and
      specific amino acids, which we call "bridge peptide" (BP). We conclude that
      translation should have emerged at the same time when the standard genetic code
      begun to evolve due to the stabilizing effect on RNA-peptide complexes with the
      help of BPs. Ribosomes, ribozymes, and the enzyme-directed RNA replication could
      co-evolve within the same period, as logical outcome of RNA-peptide world without
      the need of RNA only self-sustained step.

PMID- 30279399
TI  - Characterization of Histone Genes from the Bivalve Lucina Pectinata.
AB  - Lucina pectinata is a clam that lives in sulfide-rich environments and houses
      intracellular sulfide-oxidizing endosymbionts. To identify new Lucina pectinata
      proteins, we produced libraries for genome and transcriptome sequencing and
      assembled them de novo. We searched for histone-like sequences using the Lucina
      pectinata histone H3 partial nucleotide sequence against our previously described
      genome assembly to obtain the complete coding region and identify H3 coding
      sequences from mollusk sequences in Genbank. Solen marginatus histone nucleotide
      sequences were used as query sequences using the genome and transcriptome
      assemblies to identify the Lucina pectinata H1, H2A, H2B and H4 genes and mRNAs
      and obtained the complete coding regions of the five histone genes by RT-PCR
      combined with automated Sanger DNA sequencing. The amino acid sequence
      conservation between the Lucina pectinata and Solen marginatus histones was: 77%,
      93%, 83%, 96% and 97% for H1, H2A, H2B, H3 and H4, respectively. As expected, the
      H3 and H4 proteins were the most conserved and the H1 proteins were most similar
      to H1's from aquatic organisms like Crassostrea gigas, Aplysia californica,
      Mytilus trossulus and Biomphalaria glabrata. The Lucina pectinata draft genome
      and transcriptome assemblies, obtained by semiconductor sequencing, were adequate
      for identification of conserved proteins as evidenced by our results for the
      histone genes.

PMID- 30279402
TI  - Preclinical Models of Pediatric Brain Tumors-Forging Ahead.
AB  - Approximately five out of 100,000 children from 0 to 19 years old are diagnosed
      with a brain tumor. These children are treated with medication designed for
      adults that are highly toxic to a developing brain. Those that survive are at
      high risk for a lifetime of limited physical, psychological, and cognitive
      abilities. Despite much effort, not one drug exists that was designed
      specifically for pediatric patients. Stagnant government funding and the lack of
      economic incentives for the pharmaceutical industry greatly limits preclinical
      research and the development of clinically applicable pediatric brain tumor
      models. As more data are collected, the recognition of disease sub-groups based
      on molecular heterogeneity increases the need for designing specific models
      suitable for predictive drug screening. To overcome these challenges, preclinical
      approaches will need continual enhancement. In this review, we examine the
      advantages and shortcomings of in vitro and in vivo preclinical pediatric brain
      tumor models and explore potential solutions based on past, present, and future
      strategies for improving their clinical relevancy.

PMID- 30279403
TI  - New Perspectives on the Use of Cannabis in the Treatment of Psychiatric
      Disorders.
AB  - Following the discovery of the endocannabinoid system and its potential as a
      therapeutic target for various pathological conditions, growing interest led
      researchers to investigate the role of cannabis and its derivatives for medical
      purposes. The compounds Delta9-tetrahydrocannabinol and cannabidiol are the most
      abundant phytocannabinoids found in cannabis extracts, as well as the most
      studied. The present review aims to provide an overview of the current evidence
      for their beneficial effects in treating psychiatric disorders, including
      schizophrenia, anxiety, and depression. Nevertheless, further investigations are
      required to clarify many pending issues, especially those relative to the
      assessment of benefits and risks when using cannabis for therapeutic purposes,
      thereby also helping national and federal jurisdictions to remain updated.

PMID- 30279404
TI  - Identification of Differentially Expressed Genes in BALB/c Mouse Liver upon
      Primary Infection with DENV1 and Sequential Heterologous Infection with DENV2.
AB  - Dengue virus (DENV) results in 100 million cases of infections and 22,000 deaths
      per year. Liver involvement, thrombocytopenia, haemorrhage and plasma leakage are
      characteristic manifestations of severe forms of DENV infection. However, the
      molecular pathways of DENV infection have not been comprehensively studied
      compared to the host immunological responses. We performed an in vivo study using
      the BALB/c mouse model with a modified mRNA differential display methodology
      (GeneFishingTM) using the annealing control primer (ACP) system to capture
      differentially expressed genes (DEGs) in mice liver upon primary infection with
      DENV1 and sequential heterologous infection with DENV2. Secondary heterologous
      infection with DENV2 was carried out at Immunoglobulin IgM and IgG peaks
      following the primary DENV1 infection with the hope of determining any potential
      effect antibodies IgM and IgG may have on sequential heterologous infection. 30
      DEGs were identified and sequenced across all three treatment groups and they
      belong to a variety of important pathways such as apoptosis, innate immune
      response, inflammatory response, metabolic processes and oxidative stress.
      Analysis of differentially expressed genes in response to viral infection offers
      valuable knowledge about the dynamic and complex association between host cell
      and the virus. Furthermore, some DEGs identified support DENV induced liver
      damage.

PMID- 30279405
TI  - Polymeric Nanocarriers for the Delivery of Antimalarials.
AB  - Malaria is an infectious disease caused by a protozoan parasite which is
      transmitted by female Anopheles mosquitoes around tropical and sub-tropical
      regions. Half of the world's population is at risk of being infected by malaria.
      This mainly includes children, pregnant women and people living with chronic
      diseases. The main factor that has contributed to the spread of this disease is
      the increase in the number of drug-resistant parasites. To overcome drug
      resistance, researchers have developed drug delivery systems from biodegradable
      polymers for the loading of antimalarials. The drug delivery systems were
      characterized by distinct features such as good biocompatibility, high percentage
      drug encapsulation, reduced drug toxicity and targeted drug delivery. In this
      review article, we highlight the various types of drug delivery systems developed
      from polymeric nanocarriers used for the delivery of antimalarials.

PMID- 30279406
TI  - Development of a Rapid Fluorescent Immunochromatographic Test to Detect
      Respiratory Syncytial Virus.
AB  - Human respiratory syncytial virus (RSV) is one of the most common viruses
      infecting the respiratory tracts of infants. The rapid and sensitive detection of
      RSV is important to minimize the incidence of infection. In this study, novel
      monoclonal antibodies (mAbs; B11A5 and E8A11) against RSV nucleoprotein (NP) were
      developed and applied to develop a rapid fluorescent immunochromatographic strip
      test (FICT), employing europium nanoparticles as the fluorescent material. For
      the FICT, the limits of detection of the antigen and virus were 1.25 ug/mL and
      4.23 * 106 TCID50/mL, respectively, corresponding to 4.75 * 106 +/- 5.8 *105
      (mean +/- SD) RNA copy numbers per reaction mixture for RSV NP. A clinical study
      revealed a sensitivity of 90% (18/20) and specificity of 98.18% (108/110) for RSV
      detection when comparing the performance to that of reverse transcription
      polymerase chain reaction (RT-PCR), representing a 15% improvement in sensitivity
      over the SD Bioline rapid kit. This newly developed FICT could be a useful tool
      for the rapid diagnosis of RSV infection.

PMID- 30279407
TI  - Association of ERCC2 Gene Polymorphisms with Susceptibility to Diffuse Large B
      Cell Lymphoma.
AB  - BACKGROUND The objective of this study was to detect the association between ERCC
      excision repair 2, TFIIH core complex helicase subunit (ERCC2) gene polymorphisms
      and diffuse large B-cell lymphoma (DLBCL) susceptibility. MATERIAL AND METHODS
      This study used a case-control design. ERCC2 gene rs1799793 (Asp312Asn) and
      rs13181 (Lys751Gln) polymorphisms were genotyped by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) both in DLBCL patients and
      healthy controls. The association between ERCC2 gene polymorphisms and DLBCL risk
      was assessed by chi2 test. Odds ratios (ORs) with corresponding 95% confidence
      intervals (95% CIs) were used to address the association strength. Subgroup
      analyses were also performed to investigate the genetic effects of ERCC2
      polymorphisms on clinical characteristics of DLBCL patients. RESULTS A
      significant association was discovered between the rs1799793 A allele and
      increased DLBCL risk (P=0.031, OR=1.928, 95% CI=1.052-3.534). The C allele of
      rs13181 was obviously associated with elevated DLBCL susceptibility (P=0.047,
      OR=1.820, 95% CI=1.002-3.305). The subgroup analysis demonstrated that rs1799793
      and rs13181 polymorphisms had no relationship with serum lactate dehydrogenase
      level, nidus number, B-symptoms, Ann Arbor stages, or immunological types in
      DLBCL cases (P>0.05 for all). CONCLUSIONS Minor allele carriers of ERCC2 gene
      rs1799793 (Asp312Asn) and rs13181 (Lys751Gln) polymorphisms had higher
      susceptibility to DLBCL.

PMID- 30279408
TI  - Endoscopic Retrograde Cholangiopancreatography (ERCP) with Laparotomic Small
      Intestinal Incision Approach for Extraction of a Common Bile Duct (CBD) Stone
      Following Total Gastrectomy and Roux-en-Y (R-Y) Anastomosis: A Case Report.
AB  - BACKGROUND Endoscopic retrograde cholangiopancreatography for common bile duct
      stone in patients who underwent gastrectomy and Roux-en-Y anastomosis is
      challenging. We report a case in which we performed endoscopic retrograde
      cholangiopancreatography through a small-intestinal incision approach for a
      common bile duct stone, which had developed after total gastrectomy and Roux-en-Y
      anastomosis. CASE REPORT An 86-year-old woman with a history of laparoscopic
      assisted total gastrectomy and R-Y anastomosis and incision of the common bile
      duct and cholecystectomy for common bile duct stone by open surgery 3 years ago
      presented with abdominal pain. Examination revealed a 10-mm stone in the lower
      part of common bile duct. We planned a combined endoscopic and open surgical
      approach. An incision on the Y limb of the Roux-en-Y anastomosis 20 cm from the
      jejunojejunal anastomosis and insertion of an endoscope through this opening were
      performed to extract the common bile duct stone. The patient was discharged on
      postoperative day 22 without complications. CONCLUSIONS For a patient with a
      common bile duct stone, who underwent gastrectomy and Roux-en-Y anastomosis, with
      firm adhesions at the porta hepatis, combined endoscopy and open surgery using a
      small-intestinal incision approach can be effective when small-bowel endoscopes
      are unavailable or the cannulation to Vater's papilla by them is difficult.

PMID- 30279409
TI  - In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom
      by oligoclonal human IgG antibodies.
AB  - The black mamba (Dendroaspis polylepis) is one of the most feared snake species
      of the African savanna. It has a potent, fast-acting neurotoxic venom comprised
      of dendrotoxins and alpha-neurotoxins associated with high fatality in untreated
      victims. Current antivenoms are both scarce on the African continent and present
      a number of drawbacks as they are derived from the plasma of hyper-immunized
      large mammals. Here, we describe the development of an experimental recombinant
      antivenom by a combined toxicovenomics and phage display approach. The
      recombinant antivenom is based on a cocktail of fully human immunoglobulin G
      (IgG) monoclonal antibodies capable of neutralizing dendrotoxin-mediated
      neurotoxicity of black mamba whole venom in a rodent model. Our results show the
      potential use of fully human monoclonal IgGs against animal toxins and the first
      use of oligoclonal human IgG mixtures against experimental snakebite envenoming.

PMID- 30279410
TI  - A polygenic p factor for major psychiatric disorders.
AB  - It has recently been proposed that a single dimension, called the p factor, can
      capture a person's liability to mental disorder. Relevant to the p hypothesis,
      recent genetic research has found surprisingly high genetic correlations between
      pairs of psychiatric disorders. Here, for the first time, we compare genetic
      correlations from different methods and examine their support for a genetic p
      factor. We tested the hypothesis of a genetic p factor by applying principal
      component analysis to matrices of genetic correlations between major psychiatric
      disorders estimated by three methods-family study, genome-wide complex trait
      analysis, and linkage-disequilibrium score regression-and on a matrix of
      polygenic score correlations constructed for each individual in a UK
      representative sample of 7 026 unrelated individuals. All disorders loaded
      positively on a first unrotated principal component, which accounted for 57, 43,
      35, and 22% of the variance respectively for the four methods. Our results showed
      that all four methods provided strong support for a genetic p factor that
      represents the pinnacle of the hierarchical genetic architecture of
      psychopathology.

PMID- 30279411
TI  - Observing of the super-Planckian near-field thermal radiation between graphene
      sheets.
AB  - Thermal radiation can be substantially enhanced in the near-field scenario due to
      the tunneling of evanescent waves. Monolayer graphene could play a vital role in
      this process owing to its strong infrared plasmonic response, however, which
      still lacks an experimental verification due to the technical challenges. Here,
      we manage to make a direct measurement about plasmon-mediated thermal radiation
      between two macroscopic graphene sheets using a custom-made setup. Super
      Planckian radiation with efficiency 4.5 times larger than the blackbody limit is
      observed at a 430-nm vacuum gap on insulating silicon hosting substrates. The
      positive role of graphene plasmons is further confirmed on conductive silicon
      substrates which have strong infrared loss and thermal emittance. Based on these,
      a thermophotovoltaic cell made of the graphene-silicon heterostructure is lastly
      discussed. The current work validates the classic thermodynamical theory in
      treating graphene and also paves a way to pursue the application of near-field
      thermal management.

PMID- 30279412
TI  - Preventing acute asthmatic symptoms by targeting a neuronal mechanism involving
      carotid body lysophosphatidic acid receptors.
AB  - Asthma accounts for 380,000 deaths a year. Carotid body denervation has been
      shown to have a profound effect on airway hyper-responsiveness in animal models
      but a mechanistic explanation is lacking. Here we demonstrate, using a rat model
      of asthma (OVA-sensitized), that carotid body activation during airborne allergic
      provocation is caused by systemic release of lysophosphatidic acid (LPA). Carotid
      body activation by LPA involves TRPV1 and LPA-specific receptors, and induces
      parasympathetic (vagal) activity. We demonstrate that this activation is
      sufficient to cause acute bronchoconstriction. Moreover, we show that
      prophylactic administration of TRPV1 (AMG9810) and LPA (BrP-LPA) receptor
      antagonists prevents bradykinin-induced asthmatic bronchoconstriction and, if
      administered following allergen exposure, reduces the associated respiratory
      distress. Our discovery provides mechanistic insight into the critical roles of
      carotid body LPA receptors in allergen-induced respiratory distress and suggests
      alternate treatment options for asthma.

PMID- 30279413
TI  - Cdk1 inactivation induces post-anaphase-onset spindle migration and membrane
      protrusion required for extreme asymmetry in mouse oocytes.
AB  - Female meiotic divisions are extremely asymmetric, producing large oocytes and
      small polar bodies (PBs). In mouse oocytes, the spindle relocates to the cortex
      before anaphase of meiosis I (MI). It is presumed that by displacing the future
      midzone, pre-anaphase spindle repositioning alone ensures asymmetry. But how
      subsequent anaphase events might contribute to asymmetric PB extrusion (PBE) is
      unknown. Here, we find that inactivation of cyclin-dependent kinase 1 (Cdk1)
      induces anaphase and simultaneously triggers cytoplasmic formin-mediated F-actin
      polymerisation that propels the spindle into the cortex causing it to protrude
      while anaphase progresses. Significantly, if post-anaphase-onset spindle
      migration fails, protrusion and asymmetry are severely threatened even with
      intact pre-anaphase migration. Conversely, post-anaphase migration can completely
      compensate for failed pre-anaphase migration. These data identify a cell-cycle
      triggered phase of spindle displacement occurring after anaphase-onset, which, by
      inducing protrusion, is necessary for extreme asymmetry in mouse oocytes and
      uncover a pathway for maximising unequal division.

PMID- 30279414
TI  - Publisher Correction: Necroptosis mediates myofibre death in dystrophin-deficient
      mice.
AB  - The original version of this article contained an error in Fig. 3. In panel c,
      the labels 'mdx' and 'mdx Ripk3-/-' were inadvertently inverted. This has now
      been corrected in the PDF and HTML versions of the Article.

PMID- 30279415
TI  - Molecular architecture and regulation of BCL10-MALT1 filaments.
AB  - The CARD11-BCL10-MALT1 (CBM) complex triggers the adaptive immune response in
      lymphocytes and lymphoma cells. CARD11/CARMA1 acts as a molecular seed inducing
      BCL10 filaments, but the integration of MALT1 and the assembly of a functional
      CBM complex has remained elusive. Using cryo-EM we solved the helical structure
      of the BCL10-MALT1 filament. The structural model of the filament core solved at
      4.9 A resolution identified the interface between the N-terminal MALT1 DD and the
      BCL10 caspase recruitment domain. The C-terminal MALT1 Ig and paracaspase domains
      protrude from this core to orchestrate binding of mediators and substrates at the
      filament periphery. Mutagenesis studies support the importance of the identified
      BCL10-MALT1 interface for CBM complex assembly, MALT1 protease activation and NF
      kappaB signaling in Jurkat and primary CD4 T-cells. Collectively, we present a
      model for the assembly and architecture of the CBM signaling complex and how it
      functions as a signaling hub in T-lymphocytes.

PMID- 30279416
TI  - Two-dimensional amorphous NiO as a plasmonic photocatalyst for solar H2
      evolution.
AB  - Amorphous materials are usually evaluated as photocatalytically inactive due to
      the amorphous nature-induced self-trapping of tail states, in spite of their
      achievements in electrochemistry. NiO crystals fail to act as an individual
      reactor for photocatalytic H2 evolution because of the intrinsic hole doping,
      regardless of their impressive cocatalytic ability for proton/electron transfer.
      Here we demonstrate that two-dimensional amorphous NiO nanostructure can act as
      an efficient and robust photocatalyst for solar H2 evolution without any
      cocatalysts. Further, the antenna effect of surface plasmon resonance can be
      introduced to construct an incorporate antenna-reactor structure by increasing
      the electron doping. The solar H2 evolution rate is improved by a factor of 19.4
      through the surface plasmon resonance-mediated charge releasing. These findings
      thus open a door to applications of two-dimensional amorphous NiO as an advanced
      photocatalyst.

PMID- 30279417
TI  - Dye-incorporated coordination polymers for direct photocatalytic
      trifluoromethylation of aromatics at metabolically susceptible positions.
AB  - Direct trifluoromethylation of unactivated aromatic rings at metabolically
      susceptible positions is highly desirable in pharmaceutical applications. By
      incorporating thiophenes into the backbone of triphenylamine to enlarge its pi
      system, a new approach for constructing coordination polymers is reported for
      direct trifluoromethylation without prefunctionalization of the aryl precursors.
      The improved light-harvesting ability and well-modulated excited state redox
      potential of the designed polymers endow the generated CF3 radicals with suitable
      reactivity and enhance radical adduct oxidation in pores. The well-configurated
      interactions between the organic ligands distort the coordination geometry to
      create active interaction sites within the coordination polymer; thus, the
      substrates could be docked near the photoredox-active centres. The synergistic
      electronic and spatial effects in the confined pores balance the contradictory
      demands of electronic effects and reaction dynamics, achieving regio- and
      diastereoselective discrimination among reaction sites with unremarkable
      electronic/steric differences.

PMID- 30279418
TI  - Clinical value of bioelectrical properties of cancerous tissue in advanced
      epithelial ovarian cancer patients.
AB  - Currently, there are no valid pre-operatively established biomarkers or
      algorithms that can accurately predict surgical and clinical outcome for patients
      with advanced epithelial ovarian cancer (EOC). In this study, we suggest that
      profiling of tumour parameters such as bioelectrical-potential and metabolites,
      detectable by electronic sensors, could facilitate the future development of
      devices to better monitor disease and predict surgical and treatment outcomes.
      Biopotential was recorded, using a potentiometric measurement system, in ex vivo
      paired non-cancerous and cancerous omental tissues from advanced stage EOC (n =
      36), and lysates collected for metabolite measurement by microdialysis.
      Consistently different biopotential values were detected in cancerous tissue
      versus non-cancerous tissue across all cases (p < 0.001). High tumour
      biopotential levels correlated with advanced tumour stage (p = 0.048) and tumour
      load, and negatively correlated with stroma. Within our EOC cohort and
      specifically the high-grade serous subtype, low biopotential levels associated
      with poorer progression-free survival (p = 0.0179, p = 0.0143 respectively).
      Changes in biopotential levels significantly correlated with common apoptosis
      related pathways. Lactate and glucose levels measured in paired tissues showed
      significantly higher lactate/glucose ratio in tissues with low biopotential (p <
      0.01, n = 12). Our study proposes the feasibility of biopotential and metabolite
      monitoring as a biomarker modality profiling EOC to predict surgical and clinical
      outcomes.

PMID- 30279419
TI  - Permissiveness to form pluripotent stem cells may be an evolutionarily derived
      characteristic in Mus musculus.
AB  - Mus musculus is the only known species from which embryonic stem cells (ESC) can
      be isolated under conditions requiring only leukemia inhibitory factor (LIF).
      Other species are non-permissive in LIF media, and form developmentally primed
      epiblast stem cells (EpiSC) similar to cells derived from post-implantation, egg
      cylinders. To evaluate whether non-permissiveness extends to induced pluripotent
      stem cells (iPSC), we derived iPSC from the eight founder strains of the mouse
      Collaborative Cross. Two strains, NOD/ShiLtJ and the WSB/EiJ, were non
      permissive, consistent with the previous classification of NOD/ShiLtJ as non
      permissive to ESC derivation. We determined non-permissiveness is recessive, and
      that non-permissive genomes do not compliment. We overcame iPSC non
      permissiveness by using GSK3B and MEK inhibitors with serum, a technique we
      termed 2iS reprogramming. Although used for ESC derivation, GSK3B and MEK
      inhibitors have not been used during iPSC reprogramming because they inhibit
      survival of progenitor differentiated cells. iPSC derived in 2iS are more
      transcriptionally similar to ESC than EpiSC, indicating that 2iS reprogramming
      acts to overcome genetic background constraints. Finally, of species tested for
      ESC or iPSC derivation, only some M. musculus strains are permissive under LIF
      culture conditions suggesting that this is an evolutionarily derived
      characteristic in the M. musculus lineage.

PMID- 30279421
TI  - Motor recruitment to the TIM23 channel's lateral gate restricts polypeptide
      release into the inner membrane.
AB  - The presequence translocase of the mitochondrial inner membrane (TIM23 complex)
      facilitates anterograde precursor transport into the matrix and lateral release
      of precursors with stop-transfer signal into the membrane (sorting). Sorting
      requires precursor exit from the translocation channel into the lipid phase
      through the lateral gate of the TIM23 complex. How the two transport modes are
      regulated and balanced against each other is unknown. Here we show that the
      import motor J-protein Pam18, which is essential for matrix import, controls
      lateral protein release into the lipid bilayer. Constitutively translocase
      associated Pam18 obstructs lateral precursor transport. Concomitantly, Mgr2,
      implicated in precursor quality control, is displaced from the translocase. We
      conclude that during motor-dependent matrix protein transport, the transmembrane
      segment of Pam18 closes the lateral gate to promote anterograde polypeptide
      movement. This finding explains why a motor-free form of the translocase
      facilitates the lateral movement of precursors with a stop-transfer signal.

PMID- 30279423
TI  - Design of polarization-insensitive high-visibility silicon-on-insulator quantum
      interferometer.
AB  - We based on integrated silicon-on-insulator platforms design the key components
      of an on-chip interferometer, beam splitter and directional coupler included,
      valid in high-visibility interference at telecommunication wavelengths. Special
      attention is given to the equal-proportion beam splitting and directional
      coupling, which is achieved by carefully designing the geometric dimension of
      multi-mode interferometer structure. The proposed interferometer facilitates low
      loss, broad operating bandwidth, anticipated large tolerance on size variation
      induced in fabrication procedures, based on a particular wafer with silicon layer
      thickness of 320 nm. The most highlight property of polarization-insensitive,
      enables the path-selective qubits generation for bi-polarization that further
      makes possible quantum key distribution using high dimensional protocols. We
      numerically demonstrate interference at 1550 nm with visibilities of 99.50% and
      93.99% for transverse-electric and transverse-magnetic polarization,
      respectively, revealing that the proposed interferometer structure is well
      capable of on-chip optical control especially in quantum optics regime.

PMID- 30279420
TI  - Dereplication of microbial metabolites through database search of mass spectra.
AB  - Natural products have traditionally been rich sources for drug discovery. In
      order to clear the road toward the discovery of unknown natural products,
      biologists need dereplication strategies that identify known ones. Here we report
      DEREPLICATOR+, an algorithm that improves on the previous approaches for
      identifying peptidic natural products, and extends them for identification of
      polyketides, terpenes, benzenoids, alkaloids, flavonoids, and other classes of
      natural products. We show that DEREPLICATOR+ can search all spectra in the
      recently launched Global Natural Products Social molecular network and identify
      an order of magnitude more natural products than previous dereplication efforts.
      We further demonstrate that DEREPLICATOR+ enables cross-validation of genome
      mining and peptidogenomics/glycogenomics results.

PMID- 30279422
TI  - The potential of eye-tracking as a sensitive measure of behavioural change in
      response to intervention.
AB  - One challenge to the development of effective interventions to support learning
      and behavioural change in neurodevelopmental disorders is a lack of suitable
      outcome measures. Eye-tracking has been used widely to chart cognitive
      development and clinically-relevant group differences in many populations. This
      proof-of-concept study investigates whether it also has the potential to act as a
      marker of treatment effects, by testing its sensitivity to differential change
      over a short period of exposure to an iPad app in typically developing children.
      The app targets a key skill in early social communication development, by
      rewarding attention to people, operationalised via a finger-tap on screen. We
      measured attention to images taken from the app, and a selection of matched
      stimuli to test generalisation of effects, at baseline and two weeks later.
      Children were assigned to either an app-exposure or no-app condition in the
      intervening period. The app exposure group showed increases in fixation on people
      for images from the app, and for distant-generalisation photographs, at high
      levels of complexity. We conclude that, with careful selection of stimuli, eye
      tracking has the potential to make a valuable contribution to the range of
      outcome measures available for psycho-behavioural interventions in
      neurodevelopmental disorders.

PMID- 30279424
TI  - Electromagnetic Fields Due to the Wake of a Moving Slender Body in a Finite-Depth
      Ocean with Density Stratification.
AB  - Weak electric currents are induced in moving seawater by cutting the geomagnetic
      fields. These electric currents can produce measurable electromagnetic fields
      that may be used for some purposes such as monitoring of ocean internal waves.
      This article is aimed at presenting the procedure to calculate the
      electromagnetic fields owing to the wake raised by an undersea moving slender
      body. A pair of Havelock point sources are introduced to model the moving body,
      which generate the similar wake at places far from the body. The ocean is taken
      to be of finite-depth with density stratification due to thermocline. Three
      distinct forms of water-flow wake can be identified, the free-surface Kelvin
      wake, the internal interfacial wake, and the localized volume wake. The electric
      currents evoked by the motional wake may produce observable electromagnetic
      fields, which may be solved using rigorous electromagnetic field theory. At the
      sea level, the magnitudes of the induced electric field and magnetic field are on
      the order of a few microvolts per meter and one nano-Tesla, respectively, which
      are appreciable in terms of nowadays marine electric and magnetic sensors.

PMID- 30279425
TI  - Increased TIMP-3 expression alters the cellular secretome through dual inhibition
      of the metalloprotease ADAM10 and ligand-binding of the LRP-1 receptor.
AB  - The tissue inhibitor of metalloproteinases-3 (TIMP-3) is a major regulator of
      extracellular matrix turnover and protein shedding by inhibiting different
      classes of metalloproteinases, including disintegrin metalloproteinases (ADAMs).
      Tissue bioavailability of TIMP-3 is regulated by the endocytic receptor low
      density-lipoprotein receptor-related protein-1 (LRP-1). TIMP-3 plays protective
      roles in disease. Thus, different approaches have been developed aiming to
      increase TIMP-3 bioavailability, yet overall effects of increased TIMP-3 in vivo
      have not been investigated. Herein, by using unbiased mass-spectrometry we
      demonstrate that TIMP-3-overexpression in HEK293 cells has a dual effect on
      shedding of transmembrane proteins and turnover of soluble proteins. Several
      membrane proteins showing reduced shedding are known as ADAM10 substrates,
      suggesting that exogenous TIMP-3 preferentially inhibits ADAM10 in HEK293 cells.
      Additionally identified shed membrane proteins may be novel ADAM10 substrate
      candidates. TIMP-3-overexpression also increased extracellular levels of several
      soluble proteins, including TIMP-1, MIF and SPARC. Levels of these proteins
      similarly increased upon LRP-1 inactivation, suggesting that TIMP-3 increases
      soluble protein levels by competing for their binding to LRP-1 and their
      subsequent internalization. In conclusion, our study reveals that increased
      levels of TIMP-3 induce substantial modifications in the cellular secretome and
      that TIMP-3-based therapies may potentially provoke undesired, dysregulated
      functions of ADAM10 and LRP-1.

PMID- 30279426
TI  - OligoPVP: Phenotype-driven analysis of individual genomic information to
      prioritize oligogenic disease variants.
AB  - An increasing number of disorders have been identified for which two or more
      distinct alleles in two or more genes are required to either cause the disease or
      to significantly modify its onset, severity or phenotype. It is difficult to
      discover such interactions using existing approaches. The purpose of our work is
      to develop and evaluate a system that can identify combinations of alleles
      underlying digenic and oligogenic diseases in individual whole exome or whole
      genome sequences. Information that links patient phenotypes to databases of gene
      phenotype associations observed in clinical or non-human model organism research
      can provide useful information and improve variant prioritization for genetic
      diseases. Additional background knowledge about interactions between genes can be
      utilized to identify sets of variants in different genes in the same individual
      which may then contribute to the overall disease phenotype. We have developed
      OligoPVP, an algorithm that can be used to prioritize causative combinations of
      variants in digenic and oligogenic diseases, using whole exome or whole genome
      sequences together with patient phenotypes as input. We demonstrate that OligoPVP
      has significantly improved performance when compared to state of the art
      pathogenicity detection methods in the case of digenic diseases. Our results show
      that OligoPVP can efficiently prioritize sets of variants in digenic diseases
      using a phenotype-driven approach and identify etiologically important variants
      in whole genomes. OligoPVP naturally extends to oligogenic disease involving
      interactions between variants in two or more genes. It can be applied to the
      identification of multiple interacting candidate variants contributing to
      phenotype, where the action of modifier genes is suspected from pedigree analysis
      or failure of traditional causative variant identification.

PMID- 30279427
TI  - The terpenes of leaves, pollen, and nectar of thyme (Thymus vulgaris) inhibit
      growth of bee disease-associated microbes.
AB  - Honey bees are highly prone to infectious diseases, causing colony losses in the
      worst case. However, they combat diseases through a combination of their innate
      immune system and social defence behaviours like foraging for health-enhancing
      plant products (e.g. nectar, pollen and resin). Plant secondary metabolites are
      not only highly active against bacteria and fungi, they might even enhance
      selective foraging and feeding decisions in the colony. Here, we tested six major
      plant terpenes and their corresponding acetates, characterizing six natural
      Thymus vulgaris chemotypes, for their antimicrobial activity on bacteria
      associated with European foulbrood. Comparison of the inhibitory activity
      revealed the highest activity for carvacrol and thymol whereas the acetates
      mostly did not inhibit bacterial growth. All terpenes and acetates are present in
      the nectar and pollen of thyme, with pollen containing concentrations higher by
      several orders of magnitude. The physiological response was tested on forager and
      freshly emerged bees by means of antennal electroantennography. Both responded
      much stronger to geraniol and trans-sabinene hydrate compared to carvacrol and
      thymol. In conclusion, bee-forageable thyme product terpenes (mainly from pollen)
      yield effective antibiotic activity by reducing the growth of bee disease
      associated bacteria and can be detected with different response levels by the
      honey bees' antennae. This is a further step forward in understanding the complex
      pathogen-pollinator-plant network.

PMID- 30279428
TI  - Exposure to heat-stress environment affects the physiology, circulation levels of
      cytokines, and microbiome in dairy cows.
AB  - The microbiome has emerged as a new player on behavior, physiology and stress
      because of its significant effects on the brain-gut axis. The aim of this study
      was to increase our understanding of brain-gut function in dairy cows. We
      investigated the effects of a heat-stress (HS) environment and individual
      differences of heat sensitivity (IH) on bovine physiological characteristics and
      microbial composition. Results indicate that both HS and IH increased rectal
      temperature (RT) (P < 0.05). An HS environment increased plasma, as well as milk
      cortisol and cytokines in plasma; however, it decreased plasma, and milk
      oxytocin, triiodothyronine, and thyroxine (P < 0.05) levels. Exposure to an HS
      environment reduced the diversity of the fecal microbial population, and resulted
      in a higher expression of diseases, the environmental adaptation pathway, and the
      immune related pathway, whereas it lowered the expression of metabolic pathways
      (P < 0.05). High heat sensitive cows have upregulated metabolisms, environmental
      adaptation and cellular process pathways, and a downregulated neurodegenerative
      disease pathway (P < 0.05). Thus, we conclude that exposure to an HS environment
      modulates physiological characteristics, which may interplay with microbial
      activity, and in turn, alter the circulation levels of cytokines, implicating the
      role of the brain-gut axis in dairy cows. The HS environment affected
      physiological characteristics, cytokine levels, and microbial composition, but IH
      influenced RT and fecal microbial functions.

PMID- 30279429
TI  - Computerised Dynamic Posturography in Premanifest and Manifest individuals with
      Huntington's Disease.
AB  - Evidence from small-scale studies indicates that impairments in postural
      stability are an early and disabling feature of Huntington's disease (HD) and may
      be a useful clinical endpoint for disease modifying trials. Larger studies are
      needed to confirm these preliminary findings and the suitability of postural
      stability outcomes as clinical endpoints. Static and dynamic postural stability
      were evaluated in 54 premanifest HD, 36 manifest HD and 45 healthy individuals
      using the Sensory Organization Test (SOT) and Limits of Stability (LOS) test.
      Manifest HD displayed significantly lower scores on all SOT conditions and on the
      SOT composite score and had more falls than healthy and premanifest HD (p <
      0.05). Premanifest and manifest HD demonstrated significantly lower endpoint
      excursion (p < 0.001), maximum excursion (p <= 0.001), and directional control (p
      <= 0.004) values than healthy individuals on the LOS test. Deficits in LOS were
      found to manifest on the left side of premanifest HD. Significant but low
      associations were observed between UHDRS-TMS, disease burden score, diagnostic
      confidence level, SOT conditions and SOT composite score. We confirm here that
      individuals with premanifest and manifest HD display significant impairments in
      static and dynamic postural stability. Dynamic posturography assessments should
      be considered as clinical endpoints for future disease modifying trials.

PMID- 30279430
TI  - A novel ulvan lyase family with broad-spectrum activity from the ulvan
      utilisation loci of Formosa agariphila KMM 3901.
AB  - Ulvan, which is one of the major structural polysaccharides of the cell walls of
      green macroalgae, is degraded by ulvan lyases via the beta-elimination mechanism
      with the release of oligosaccharides that have unsaturated 4-deoxy-L-threo-hex-4
      enopyranosiduronic acid (?) at the non-reducing end. These ulvan lyases belong to
      the PL24 or PL25 or PL28 family in the CAZy database. In this study, we identify
      and biochemically characterise a periplasmic novel broad-spectrum ulvan lyase
      from Formosa agariphila KMM 3901. The lyase was overexpressed in Escherichia
      coli, and the purified recombinant enzyme depolymerised ulvan in an endolytic
      manner with a Km of 0.77 mg/ml, and displayed optimum activity at 40  degrees C
      and pH 8. This lyase also degraded heparan sulphate and chondroitin sulphate.
      Detailed analyses of the end-products of the enzymatic degradation of ulvan using
      1H- and 13C-NMR and LC-MS revealed an unsaturated disaccharide (?Rha3S) and a
      tetrasaccharide (?Rha3S-Xyl-Rha) as the principal end-products. In contrast to
      the previously described ulvan lyases, this novel lyase is mostly composed of
      alpha-helices that form an (alpha/alpha)6 incomplete toroid domain and displays a
      remarkably broad-spectrum activity. This novel lyase is the first member of a new
      family of ulvan lyases.

PMID- 30279431
TI  - The role of scene summary statistics in object recognition.
AB  - Objects that are semantically related to the visual scene context are typically
      better recognized than unrelated objects. While context effects on object
      recognition are well studied, the question which particular visual information of
      an object's surroundings modulates its semantic processing is still unresolved.
      Typically, one would expect contextual influences to arise from high-level,
      semantic components of a scene but what if even low-level features could modulate
      object processing? Here, we generated seemingly meaningless textures of real
      world scenes, which preserved similar summary statistics but discarded spatial
      layout information. In Experiment 1, participants categorized such textures
      better than colour controls that lacked higher-order scene statistics while
      original scenes resulted in the highest performance. In Experiment 2,
      participants recognized briefly presented consistent objects on scenes
      significantly better than inconsistent objects, whereas on textures, consistent
      objects were recognized only slightly more accurately. In Experiment 3, we
      recorded event-related potentials and observed a pronounced mid-central
      negativity in the N300/N400 time windows for inconsistent relative to consistent
      objects on scenes. Critically, inconsistent objects on textures also triggered
      N300/N400 effects with a comparable time course, though less pronounced. Our
      results suggest that a scene's low-level features contribute to the effective
      processing of objects in complex real-world environments.

PMID- 30279432
TI  - 3D laser nano-printing on fibre paves the way for super-focusing of multimode
      laser radiation.
AB  - Multimode high-power laser diodes suffer from inefficient beam focusing, leading
      to a focal spot 10-100 times greater than the diffraction limit. This inevitably
      restricts their wider use in 'direct-diode' applications in materials processing
      and biomedical photonics. We report here a 'super-focusing' characteristic for
      laser diodes, where the exploitation of self-interference of modes enables a
      significant reduction of the focal spot size. This is achieved by employing a
      conical microlens fabricated on the tip of a multimode optical fibre using 3D
      laser nano-printing (also known as multi-photon lithography). When refracted by
      the conical surface, the modes of the fibre-coupled laser beam self-interfere and
      form an elongated narrow focus, usually referred to as a 'needle' beam. The
      multiphoton lithography technique allows the realisation of almost any optical
      element on a fibre tip, thus providing the most suitable interface for free-space
      applications of multimode fibre-delivered laser beams. In addition, we
      demonstrate the optical trapping of microscopic objects with a super-focused
      multimode laser diode beam thus rising new opportunities within the applications
      sector where lab-on-chip configurations can be exploited. Most importantly, the
      demonstrated super-focusing approach opens up new avenues for the 'direct-diode'
      applications in material processing and 3D printing, where both high power and
      tight focusing is required.

PMID- 30279433
TI  - Single shot femtosecond laser nano-ablation of CVD monolayer graphene.
AB  - We investigate ablation of CVD monolayer graphene by femtosecond pulses in the
      single shot regime. We show that the ablation probability of flat graphene
      drastically reduces for small illumination diameters even if the ablation
      threshold is exceeded. However, the presence of graphene wrinkles enhances the
      ablation probability. This is interpreted in terms of electron and energy
      diffusion within the graphene layer. This differentiated behavior is a drawback
      for single shot laser nanopatterning. The morphology of the holes with minimal
      diameter depends on the fluence distribution at ablation threshold. Strong
      fluence gradients due to strong focussing produce an explosive folding of
      graphene during ablation.

PMID- 30279434
TI  - Detection and characterization of traumatic bile leaks using Gd-EOB-DTPA enhanced
      magnetic resonance cholangiography.
AB  - Expanding bile leaks after blunt liver trauma require more aggressive treatment
      than contained bile leaks. In this retrospective study approved by institution
      review board, we analyzed if non-invasive contrast-enhanced magnetic resonance
      cholangiography (CEMRC) using hepatocyte-specific contrast agent (gadoxetic acid
      disodium) could detect and characterize traumatic bile leaks. Between March 2012
      and December 2014, written informed consents from 22 included patients (17 men, 5
      women) with a median age of 24.5 years (IQR 21.8, 36.0 years) were obtained.
      Biliary tree visualization and bile leak detection on CEMRC acquired at 10, 20,
      30, 90 minutes time points were independently graded by three radiologists on a 5
      point Likert scale. Intraclass Correlation (ICC) was computed as estimates of
      interrater reliability. Accuracy was measured by area under receiver operating
      characteristic curves (AUROC). Biliary tree visualization was the best on CEMRC
      at 90 minutes (score 4.30) with excellent inter-rater reliability (ICC = 0.930).
      Of 22 CEMRC, 15 had bile leak (8 expanding, 7 contained). The largest AUROC of
      bile leak detection by three radiologists were 0.824, 0.914, 0.929 respectively
      on CEMRC at 90 minutes with ICC of 0.816. In conclusion, bile leaks of blunt
      liver trauma can be accurately detected and characterized on CEMRC.

PMID- 30279436
TI  - Longitudinal analysis of biomarker data from a personalized nutrition platform in
      healthy subjects.
AB  - The trend toward personalized approaches to health and medicine has resulted in a
      need to collect high-dimensional datasets on individuals from a wide variety of
      populations, in order to generate customized intervention strategies. However, it
      is not always clear whether insights derived from studies in patient populations
      or in controlled trial settings are transferable to individuals in the general
      population. To address this issue, a longitudinal analysis was conducted on blood
      biomarker data from 1032 generally healthy individuals who used an automated, web
      based personalized nutrition and lifestyle platform. The study had two main aims:
      to analyze correlations between biomarkers for biological insights, and to
      characterize the effectiveness of the platform in improving biomarker levels.
      First, a biomarker correlation network was constructed to generate biological
      hypotheses that are relevant to researchers and, potentially, to users of
      personalized wellness tools. The correlation network revealed expected patterns,
      such as the established relationships between blood lipid levels, as well as
      novel insights, such as a connection between neutrophil and triglyceride
      concentrations that has been suggested as a relevant indicator of cardiovascular
      risk. Next, biomarker changes during platform use were assessed, showing a trend
      toward normalcy for most biomarkers in those participants whose values were out
      of the clinically normal range at baseline. Finally, associations were found
      between the selection of specific interventions and corresponding biomarker
      changes, suggesting directions for future study.

PMID- 30279435
TI  - Exposure to childhood abuse is associated with human sperm DNA methylation.
AB  - Offspring of persons exposed to childhood abuse are at higher risk of
      neurodevelopmental and physical health disparities across the life course. Animal
      experiments have indicated that paternal environmental stressors can affect sperm
      DNA methylation and gene expression in an offspring. Childhood abuse has been
      associated with epigenetic marks in human blood, saliva, and brain tissue, with
      statistically significant methylation differences ranging widely. However, no
      studies have examined the association of childhood abuse with DNA methylation in
      gametes. We examined the association of childhood abuse with DNA methylation in
      human sperm. Combined physical, emotional, and sexual abuse in childhood was
      characterized as none, medium, or high. DNA methylation was assayed in 46 sperm
      samples from 34 men in a longitudinal non-clinical cohort using
      HumanMethylation450 BeadChips. We performed principal component analysis and
      examined the correlation of principal components with abuse exposure. Childhood
      abuse was associated with a component that captured 6.2% of total variance in DNA
      methylation (p < 0.05). Next, we investigated the regions differentially
      methylated by abuse exposure. We identified 12 DNA regions differentially
      methylated by childhood abuse, containing 64 probes and including sites on genes
      associated with neuronal function (MAPT, CLU), fat cell regulation (PRDM16), and
      immune function (SDK1). We examined adulthood health behaviors, mental health,
      and trauma exposure as potential mediators of an association between abuse and
      DNAm, and found that mental health and trauma exposure partly mediated the
      association. Finally, we constructed a parsimonious epigenetic marker for
      childhood abuse using a machine learning approach, which identified three probes
      that predicted high vs. no childhood abuse in 71% of participants. Our results
      suggested that childhood abuse is associated with sperm DNA methylation, which
      may have implications for offspring development. Larger samples are needed to
      identify with greater confidence specific genomic regions differentially
      methylated by childhood abuse.

PMID- 30279437
TI  - Mesenchymal stem cells are attracted to latent HIV-1-infected cells and enable
      virus reactivation via a non-canonical PI3K-NFkappaB signaling pathway.
AB  - Persistence of latent HIV-1 in macrophages (MACs) and T-helper lymphocytes (THLs)
      remain a major therapeutic challenge. Currently available latency reversing
      agents (LRAs) are not very effective in vivo. Therefore, understanding of
      physiologic mechanisms that dictate HIV-1 latency/reactivation in reservoirs is
      clearly needed. Mesenchymal stromal/stem cells (MSCs) regulate the function of
      immune cells; however, their role in regulating virus production from latently
      infected MACs & THLs is not known. We documented that exposure to MSCs or their
      conditioned media (MSC-CM) rapidly increased HIV-1 p24 production from the
      latently-infected U1 (MAC) & ACH2 (THL) cell lines. Exposure to MSCs also
      increased HIV-1 long terminal repeat (LTR) directed gene expression in the MAC
      and THL reporter lines, U937-VRX and J-Lat (9.2), respectively. MSCs exposed to
      CM from U1 cells (U1-CM) showed enhanced migratory ability towards latently
      infected cells and retained their latency-reactivation potential. Molecular
      studies showed that MSC-mediated latency-reactivation was dependent upon both the
      phosphatidyl inositol-3-kinase (PI3K) and nuclear factor-kappaB (NFkappaB)
      signaling pathways. The pre-clinically tested inhibitors of PI3K (PX-866) and
      NFkappaB (CDDO-Me) suppressed MSC-mediated HIV-1 reactivation. Furthermore,
      coexposure to MSC-CM enhanced the latency-reactivation efficacy of the approved
      LRAs, vorinostat and panobinostat. Our findings on MSC-mediated latency
      reactivation may provide novel strategies against persistent HIV-1 reservoirs.

PMID- 30279438
TI  - Local confinement of disease-related microbiome facilitates recovery of gorgonian
      sea fans from necrotic-patch disease.
AB  - Microbiome disruptions triggering disease outbreaks are increasingly threatening
      corals worldwide. In the Tropical Eastern Pacific, a necrotic-patch disease
      affecting gorgonian corals (sea fans, Pacifigorgia spp.) has been observed in
      recent years. However, the composition of the microbiome and its disease-related
      disruptions remain unknown in these gorgonian corals. Therefore, we analysed 16S
      rRNA gene amplicons from tissues of healthy colonies (n = 19) and from
      symptomatic-asymptomatic tissues of diseased colonies (n = 19) of Pacifigorgia
      cairnsi (Gorgoniidae: Octocorallia) in order to test for disease-related changes
      in the bacterial microbiome. We found that potential endosymbionts (mostly
      Endozoicomonas spp.) dominate the core microbiome in healthy colonies. Moreover,
      healthy tissues differed in community composition and functional profile from
      those of the symptomatic tissues but did not show differences to asymptomatic
      tissues of the diseased colonies. A more diverse set of bacteria was observed in
      symptomatic tissues, together with the decline in abundance of the potential
      endosymbionts from the healthy core microbiome. Furthermore, according to a
      comparative taxonomy-based functional profiling, these symptomatic tissues were
      characterized by the increase in heterotrophic, ammonia oxidizer and
      dehalogenating bacteria and by the depletion of nitrite and sulphate reducers.
      Overall, our results suggest that the bacterial microbiome associated with the
      disease behaves opportunistically and is likely in a state of microbial
      dysbiosis. We also conclude that the confinement of the disease-related
      consortium to symptomatic tissues may facilitate colony recovery.

PMID- 30279440
TI  - Primary rat LSECs preserve their characteristic phenotype after cryopreservation.
AB  - Liver disease is a leading cause of morbidity and mortality worldwide. Recently,
      the liver non-parenchymal cells have gained increasing attention for their
      potential role in the development of liver disease. Liver sinusoidal endothelial
      cells (LSECs), a specialized type of endothelial cells that have unique
      morphology and function, play a fundamental role in maintaining liver
      homeostasis. Current protocols for LSEC isolation and cultivation rely on freshly
      isolated cells which can only be maintained differentiated in culture for a few
      days. This creates a limitation in the use of LSECs for research and a need for a
      consistent and reliable source of these cells. To date, no LSEC cryopreservation
      protocols have been reported that enable LSECs to retain their functional and
      morphological characteristics upon thawing and culturing. Here, we report a
      protocol to cryopreserve rat LSECs that, upon thawing, maintain full LSEC
      signature features: fenestrations, scavenger receptor expression and endocytic
      function on par with freshly isolated cells. We have confirmed these features by
      a combination of biochemical and functional techniques, and super-resolution
      microscopy. Our findings offer a means to standardize research using LSECs,
      opening the prospects for designing pharmacological strategies for various liver
      diseases, and considering LSECs as a therapeutic target.

PMID- 30279439
TI  - Genetic conflicts with Plasmodium parasites and functional constraints shape the
      evolution of erythrocyte cytoskeletal proteins.
AB  - Plasmodium parasites exerted a strong selective pressure on primate genomes and
      mutations in genes encoding erythrocyte cytoskeleton proteins (ECP) determine
      protective effects against Plasmodium infection/pathogenesis. We thus
      hypothesized that ECP-encoding genes have evolved in response to Plasmodium
      driven selection. We analyzed the evolutionary history of 15 ECP-encoding genes
      in primates, as well as of their Plasmodium-encoded ligands (KAHRP, MESA and
      EMP3). Results indicated that EPB42, SLC4A1, and SPTA1 evolved under pervasive
      positive selection and that episodes of positive selection tended to occur more
      frequently in primate species that host a larger number of Plasmodium parasites.
      Conversely, several genes, including ANK1 and SPTB, displayed extensive
      signatures of purifying selection in primate phylogenies, Homininae lineages, and
      human populations, suggesting strong functional constraints. Analysis of
      Plasmodium genes indicated adaptive evolution in MESA and KAHRP; in the latter,
      different positively selected sites were located in the spectrin-binding domains.
      Because most of the positively selected sites in alpha-spectrin localized to the
      domains involved in the interaction with KAHRP, we suggest that the two proteins
      are engaged in an arms-race scenario. This observation is relevant because KAHRP
      is essential for the formation of "knobs", which represent a major virulence
      determinant for P. falciparum.

PMID- 30279442
TI  - Computational design of chemogenetic and optogenetic split proteins.
AB  - Controlling protein activity with chemogenetics and optogenetics has proven to be
      powerful for testing hypotheses regarding protein function in rapid biological
      processes. Controlling proteins by splitting them and then rescuing their
      activity through inducible reassembly offers great potential to control diverse
      protein activities. Building split proteins has been difficult due to spontaneous
      assembly, difficulty in identifying appropriate split sites, and inefficient
      induction of effective reassembly. Here we present an automated approach to
      design effective split proteins regulated by a ligand or by light (SPELL). We
      develop a scoring function together with an engineered domain to enable
      reassembly of protein halves with high efficiency and with reduced spontaneous
      assembly. We demonstrate SPELL by applying it to proteins of various shapes and
      sizes in living cells. The SPELL server (spell.dokhlab.org) offers an automated
      prediction of split sites.

PMID- 30279441
TI  - Hydrogen sulfide limits neutrophil transmigration, inflammation, and oxidative
      burst in lipopolysaccharide-induced acute lung injury.
AB  - Transmigration and activation of neutrophils in the lung reflect key steps in the
      progression of acute lung injury (ALI). It is known that hydrogen sulfide (H2S)
      can limit neutrophil activation, but the respective mechanisms remain elusive.
      Here, we aimed to examine the underlying pathways in pulmonary inflammation. In
      vivo, C57BL/6N mice received the H2S slow releasing compound GYY4137 prior to
      lipopolysaccharide (LPS) inhalation. LPS challenge led to pulmonary injury,
      inflammation, and neutrophil transmigration that were inhibited in response to
      H2S pretreatment. Moreover, H2S reduced mRNA expression of macrophage
      inflammatory protein-2 (MIP-2) and its receptor in lung tissue, as well as the
      accumulation of MIP-2 and interleukin-1beta in the alveolar space. In vitro,
      GYY4137 did not exert toxic effects on Hoxb8 neutrophils, but prevented their
      transmigration through an endothelial barrier in the presence and absence of MIP
      2. In addition, the release of MIP-2 and reactive oxygen species from LPS
      stimulated Hoxb8 neutrophils were directly inhibited by H2S. Taken together, we
      provide first evidence that H2S limits lung neutrophil sequestration upon LPS
      challenge. As proposed underlying mechanisms, H2S prevents neutrophil
      transmigration through the inflamed endothelium and directly inhibits pro
      inflammatory as well as oxidative signalling in neutrophils. Subsequently, H2S
      pretreatment ameliorates LPS-induced ALI.

PMID- 30279443
TI  - Bridging of membrane surfaces by annexin A2.
AB  - The protein-mediated formation of membrane contacts is a crucial event in many
      cellular processes ranging from the establishment of organelle contacts to the
      docking of vesicles to a target membrane. Annexins are Ca2+ regulated membrane
      binding proteins implicated in providing such membrane contacts; however, the
      molecular basis of membrane bridging by annexins is not fully understood. We
      addressed this central question using annexin A2 (AnxA2) that functions in
      secretory vesicle exocytosis possibly by providing membrane bridges. By
      quantitatively analyzing membrane contact formation using a novel assay based on
      quartz crystal microbalance recordings, we show that monomeric AnxA2 can bridge
      membrane surfaces Ca2+ dependently. However, this activity depends on an
      oxidative crosslink involving a cysteine residue in the N-terminal domain and
      thus formation of disulfide-linked dimers. Alkylated AnxA2 in which this cysteine
      residue has been modified and AnxA2 mutants lacking the N-terminal domain are not
      capable of bridging membrane surfaces. In contrast, a heterotetrameric complex
      comprising two membrane binding AnxA2 subunits linked by a S100A10 dimer can
      provide membrane contacts irrespective of oxidation status. Thus, monomeric AnxA2
      only contains one lipid binding site and AnxA2-mediated linking of membrane
      surfaces under non-oxidative intracellular conditions most likely requires AnxA2
      S100 complex formation.

PMID- 30279444
TI  - Global patterns of change and variation in sea surface temperature and
      chlorophyll a.
AB  - Changes over the scale of decades in oceanic environments present a range of
      challenges for management and utilisation of ocean resources. Here we investigate
      sources of global temporal variation in Sea Surface Temperature (SST) and Ocean
      Colour (Chl-a) and their co-variation, over a 14 year period using statistical
      methodologies that partition sources of variation into inter-annual and annual
      components and explicitly account for daily auto-correlation. The variation in
      SST shows bands of increasing variability with increasing latitude, while the
      analysis of annual variability in Chl-a shows mostly mid-latitude high
      variability bands. Covariation patterns of SST and Chl-a suggests several
      different mechanisms impacting Chl-a change and variance. Our high spatial
      resolution analysis indicates these are likely to be operating at relatively
      small spatial scales. There are large regions showing warming and rising of Chl
      a, contrasting with regions that show warming and decreasing Chl-a. The
      covariation pattern in annual variation in SST and Chl-a reveals broad
      latitudinal bands. On smaller scales there are significant regional anomalies
      where upwellings are known to occur. Over decadal time scales both trend and
      variation in SST, Chl-a and their covariance is highly spatially heterogeneous,
      indicating that monitoring and resource management must be regionally
      appropriate.

PMID- 30279445
TI  - Molecular characterization and prospective isolation of human fetal cochlear hair
      cell progenitors.
AB  - Sensory hair cells located in the organ of Corti are essential for cochlear
      mechanosensation. Their loss is irreversible in humans resulting in permanent
      hearing loss. The development of therapeutic interventions for hearing loss
      requires fundamental knowledge about similarities and potential differences
      between animal models and human development as well as the establishment of human
      cell based-assays. Here we analyze gene and protein expression of the developing
      human inner ear in a temporal window spanning from week 8 to 12 post conception,
      when cochlear hair cells become specified. Utilizing surface markers for the
      cochlear prosensory domain, namely EPCAM and CD271, we purify postmitotic hair
      cell progenitors that, when placed in culture in three-dimensional organoids,
      regain proliferative potential and eventually differentiate to hair cell-like
      cells in vitro. These results provide a foundation for comparative studies with
      otic cells generated from human pluripotent stem cells and for establishing novel
      platforms for drug validation.

PMID- 30279447
TI  - Spatial Characterization of Soybean Yield and Quality (Amino Acids, Oil, and
      Protein) for United States.
AB  - Continued economic relevancy of soybean is a function of seed quality. The
      objectives of this study were to: (i) assess the spatial association between
      soybean yield and quality across major US soybean producing regions, (ii)
      investigate the relationship between protein, oil, and yield with amino acids
      (AAs) composition, and (iii) study interrelationship among essential AAs in
      soybean seed. Data from soybean testing programs conducted across 14 US states
      from 2012 to 2016 period (n = 35,101 data points) were analyzed. Results indicate
      that for each Mg ha-1 yield increase, protein yield increased by 0.35 Mg protein
      ha-1 and oil yield improved by 0.20 Mg oil ha-1. Essential AA concentrations
      exhibit a spatial autocorrelation and there was a negative relationship between
      concentration of AA, protein, and oil, with latitude. There was a positive
      interrelationship with different degree of strength among all AAs, and the
      correlation between Isoleucine and Valine was the strongest (r = 0.93) followed
      by the correlation among Arginine, Leucine, Lysine, and Threonine (0.71 < r <
      0.88). We concluded that the variability in genotype (G) x management (M) x
      environment (E) across latitudes influencing yield also affected soybean quality;
      AA, protein, and oil content in a similar manner.

PMID- 30279448
TI  - Barriers to the evaluation of evidence-based public health policy.
AB  - Public health policy has the potential to produce great benefits for individuals
      and communities. There is growing demand that such efforts be rigorously
      evaluated to ensure that the expected benefits are, in fact, realised. Commonly,
      public health policy is evaluated by consumer acceptability, reach, or changes in
      knowledge and attitudes. Non-robust research designs are often used. But these
      approaches to evaluation do not answer three critical questions: Has a change in
      the desired outcome occurred? Was it a consequence of the policy and not some
      extraneous factor? Was the size of the change considered significant and cost
      effective? We, a team of government and academic scholars working in research and
      evaluation, have examined some of the more common impediments to robust
      evaluation: political impediments, a lack of investment in evaluation capacity
      within bureaucracy, and the failure of academic researchers to understand the
      need for the evaluation of public health policy.

PMID- 30279446
TI  - Total syntheses of shizukaols A and E.
AB  - Shizukaols possess a common heptacyclic framework containing more than ten
      contiguous stereocenters and potential biological activities. Here we report that
      the total syntheses of shizukaols A (1) and E (2), two lindenane-type dimers from
      the Chloranthaceae family, are achieved via a modified biomimetic Diels-Alder
      reaction. The common crucial biomimetic diene 23 and ethylene species (6, 17) are
      obtained through either a highly Z-selective olefination of alpha-siloxy ketone
      with ynolate anions or an intramolecular Horner-Wadsworth-Emmons olefination from
      commercially available Wieland-Miescher ketone (7). This synthetic approach here
      opens up practical avenues for the total syntheses of the intriguing
      Chloranthaceae family members, as well as the understanding of their relevant
      biological action in nature.

PMID- 30279449
TI  - A stably self-renewing adult blood-derived induced neural stem cell exhibiting
      patternability and epigenetic rejuvenation.
AB  - Recent reports suggest that induced neurons (iNs), but not induced pluripotent
      stem cell (iPSC)-derived neurons, largely preserve age-associated traits. Here,
      we report on the extent of preserved epigenetic and transcriptional aging
      signatures in directly converted induced neural stem cells (iNSCs). Employing
      restricted and integration-free expression of SOX2 and c-MYC, we generated a
      fully functional, bona fide NSC population from adult blood cells that remains
      highly responsive to regional patterning cues. Upon conversion, low passage iNSCs
      display a profound loss of age-related DNA methylation signatures, which further
      erode across extended passaging, thereby approximating the DNA methylation age of
      isogenic iPSC-derived neural precursors. This epigenetic rejuvenation is
      accompanied by a lack of age-associated transcriptional signatures and absence of
      cellular aging hallmarks. We find iNSCs to be competent for modeling pathological
      protein aggregation and for neurotransplantation, depicting blood-to-NSC
      conversion as a rapid alternative route for both disease modeling and
      neuroregeneration.

PMID- 30279451
TI  - Assembly of Schizosaccharomyces cryophilus chromosomes and their comparative
      genomic analyses revealed principles of genome evolution of the haploid fission
      yeasts.
AB  - The fission yeast clade, which has a distinct life history from other yeasts, can
      provide important clues about evolutionary changes. To reveal these changes the
      large S. cryophilus supercontigs were assembled into chromosomes using synteny
      relationships and the conserved pericentromeric, subtelomeric genes. Togetherness
      of the supercontigs was confirmed by PCR. Investigation of the gene order
      revealed localisation of the rDNA arrays, more than 300 new conserved orthologues
      and proved that S. cryophilus supercontigs were mosaics of collinear blocks. PFGE
      analysis showed that size of the S. cryophilus chromosomes differ from the S.
      pombe chromosomes. Comparative genomic analyses of the newly assembled
      chromosomes confirmed that the closest relative of S. cryophilus was S.
      octosporus not just in sequence similarity but also in a structural way, and
      revealed that preservation of the conserved regions did not arise from the lower
      number of chromosomal rearrangements. Translocations were more typical in the
      closely related species, while the number of inversions increased with the
      phylogenetic distances. Our data suggested that sites of the chromosomal
      rearrangements were not random and often associated with repetitive sequences,
      structural- and nucleotide evolution might correlate. Chromosomal rearrangements
      of the fission yeasts compared to other lineages were also discussed.

PMID- 30279453
TI  - From WCLC 2018.

PMID- 30279452
TI  - Risk factors of chronic kidney diseases in Chinese adults with type 2 diabetes.
AB  - In this study we conducted a cross sectional study to comprehensively evaluated
      the risk factors of chronic kidney disease (CKD) in a large sample of Chinese
      adults under primary care for type 2 diabetes mellitus (T2DM). We investigated
      the risk factors associated with the prevalence of CKD in adults with T2DM, who
      were enrolled in the Risk Factor Assessment and Management Programme for Patients
      with Diabetes Mellitus (RAMP-DM) of Hong Kong from July 2014 to June 2017. We
      collected the individual data of 31,574 subjects, with mean age of 63.0 (+/-10.8)
      years and mean DM duration of 7.4 (+/-6.4) years. Of them 9,386 (29.7%) had CKD
      and 7,452 (23.6%) had micro- or macro-albuminuria. After adjustment for multiple
      demographic and lifestyle confounders, we identified several modifiable risk
      factors associated with higher rate of CKD: obesity (OR = 1.54), current smoking
      (OR = 1.33), higher systolic blood pressure (OR = 1.01), dyslipidemia (OR = 1.32
      and 0.61 for triglycerides (TG) and high-density lipoprotein cholesterol (HDL
      C)), hyperglycemia (OR = 1.11 for HbA1c), diabetic retinopathy (OR = 1.36 and
      2.60 for non-sight and sight threatening retinopathy), and stroke (OR = 1.43).
      The risk factors of lower dialytic blood pressure and coronary heart disease were
      identified only in men, whereas peripheral arterial disease only in women. In
      conclusion, several modifiable and gender specific risk factors were
      significantly associated with higher prevalence of CKD in Chinese adults with
      T2DM. The high-risk populations identified in this study shall receive regular
      screening for renal functions to achieve better patient management in primary
      care settings.

PMID- 30279450
TI  - A systems-approach reveals human nestin is an endothelial-enriched, angiogenesis
      independent intermediate filament protein.
AB  - The intermediate filament protein nestin is expressed during embryonic
      development, but considered largely restricted to areas of regeneration in the
      adult. Here, we perform a body-wide transcriptome and protein-profiling analysis
      to reveal that nestin is constitutively, and highly-selectively, expressed in
      adult human endothelial cells (EC), independent of proliferative status.
      Correspondingly, we demonstrate that it is not a marker for tumour EC in multiple
      malignancy types. Imaging of EC from different vascular beds reveals nestin
      subcellular distribution is shear-modulated. siRNA inhibition of nestin increases
      EC proliferation, and nestin expression is reduced in atherosclerotic plaque
      neovessels. eQTL analysis reveals an association between SNPs linked to
      cardiovascular disease and reduced aortic EC nestin mRNA expression. Our study
      challenges the dogma that nestin is a marker of proliferation, and provides
      insight into its regulation and function in EC. Furthermore, our systems-based
      approach can be applied to investigate body-wide expression profiles of any
      candidate protein.

PMID- 30279454
TI  - A novel antimicrobial peptide acting via formyl peptide receptor 2 shows
      therapeutic effects against rheumatoid arthritis.
AB  - In oriental medicine, centipede Scolopendra subspinipes mutilans has long been
      used as a remedy for rheumatoid arthritis (RA), a well-known chronic autoimmune
      disorder. However, the molecular identities of its bioactive components have not
      yet been extensively investigated. We sought to identify bioactive molecules that
      control RA with a centipede. A novel antimicrobial peptide (AMP) (scolopendrasin
      IX) was identified from Scolopendra subspinipes mutilans. Scolopendrasin IX
      markedly activated mouse neutrophils, by enhancing cytosolic calcium increase,
      chemotactic cellular migration, and generation of superoxide anion in
      neutrophils. As a target receptor for scolopendrasin IX, formyl peptide receptor
      (FPR)2 mediates neutrophil activation induced by the AMP. Furthermore,
      scolopendrasin IX administration strongly blocked the clinical phenotype of RA in
      an autoantibody-injected model. Mechanistically, the novel AMP inhibited
      inflammatory cytokine synthesis from the joints and neutrophil recruitment into
      the joint area. Collectively, we suggest that scolopendrasin IX is a novel
      potential therapeutic agent for the control of RA via FPR2.

PMID- 30279456
TI  - SSRIs target prefrontal to raphe circuits during development modulating synaptic
      connectivity and emotional behavior.
AB  - Antidepressants that block the serotonin transporter, (Slc6a4/SERT), selective
      serotonin reuptake inhibitors (SSRIs) improve mood in adults but have paradoxical
      long-term effects when administered during perinatal periods, increasing the risk
      to develop anxiety and depression. The basis for this developmental effect is not
      known. Here, we show that during an early postnatal period in mice (P0-P10),
      Slc6a4/SERT is transiently expressed in a subset of layer 5-6 pyramidal neurons
      of the prefrontal cortex (PFC). PFC-SERT+ neurons establish glutamatergic
      synapses with subcortical targets, including the serotonin (5-HT) and GABA
      neurons of the dorsal raphe nucleus (DRN). PFC-to-DRN circuits develop
      postnatally, coinciding with the period of PFC Slc6a4/SERT expression. Complete
      or cortex-specific ablation of SERT increases the number of functional PFC
      glutamate synapses on both 5-HT and GABA neurons in the DRN. This PFC-to-DRN
      hyperinnervation is replicated by early-life exposure to the SSRI, fluoxetine
      (from P2 to P14), that also causes anxiety/depressive-like symptoms. We show that
      pharmacogenetic manipulation of PFC-SERT+ neuron activity bidirectionally
      modulates these symptoms, suggesting that PFC hypofunctionality has a causal role
      in these altered responses to stress. Overall, our data identify specific PFC
      descending circuits that are targets of antidepressant drugs during development.
      We demonstrate that developmental expression of SERT in this subset of PFC
      neurons controls synaptic maturation of PFC-to-DRN circuits, and that remodeling
      of these circuits in early life modulates behavioral responses to stress in
      adulthood.

PMID- 30279455
TI  - Predictors for a dementia gene mutation based on gene-panel next-generation
      sequencing of a large dementia referral series.
AB  - Next-generation genetic sequencing (NGS) technologies facilitate the screening of
      multiple genes linked to neurodegenerative dementia, but there are few reports
      about their use in clinical practice. Which patients would most profit from
      testing, and information on the likelihood of discovery of a causal variant in a
      clinical syndrome, are conspicuously absent from the literature, mostly for a
      lack of large-scale studies. We applied a validated NGS dementia panel to 3241
      patients with dementia and healthy aged controls; 13,152 variants were classified
      by likelihood of pathogenicity. We identified 354 deleterious variants (DV, 12.6%
      of patients); 39 were novel DVs. Age at clinical onset, clinical syndrome and
      family history each strongly predict the likelihood of finding a DV, but
      healthcare setting and gender did not. DVs were frequently found in genes not
      usually associated with the clinical syndrome. Patients recruited from primary
      referral centres were compared with those seen at higher-level research centres
      and a national clinical neurogenetic laboratory; rates of discovery were
      comparable, making selection bias unlikely and the results generalisable to
      clinical practice. We estimated penetrance of DVs using large-scale online
      genomic population databases and found 71 with evidence of reduced penetrance.
      Two DVs in the same patient were found more frequently than expected. These data
      should provide a basis for more informed counselling and clinical decision
      making.

PMID- 30279457
TI  - Uncovering the complex genetics of human temperament.
AB  - Experimental studies of learning suggest that human temperament may depend on the
      molecular mechanisms for associative conditioning, which are highly conserved in
      animals. The main genetic pathways for associative conditioning are known in
      experimental animals, but have not been identified in prior genome-wide
      association studies (GWAS) of human temperament. We used a data-driven machine
      learning method for GWAS to uncover the complex genotypic-phenotypic networks and
      environmental interactions related to human temperament. In a discovery sample of
      2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs)
      that cluster within particular individuals (i.e., SNP sets) regardless of
      phenotype. Second, we identified 3 clusters of people with distinct temperament
      profiles measured by the Temperament and Character Inventory regardless of
      genotype. Third, we found 51 SNP sets that identified 736 gene loci and were
      significantly associated with temperament. The identified genes were enriched in
      pathways activated by associative conditioning in animals, including the ERK,
      PI3K, and PKC pathways. 74% of the identified genes were unique to a specific
      temperament profile. Environmental influences measured in childhood and adulthood
      had small but significant effects. We confirmed the replicability of the 51
      Finnish SNP sets in healthy Korean (90%) and German samples (89%), as well as
      their associations with temperament. The identified SNPs explained nearly all the
      heritability expected in each sample (37-53%) despite variable cultures and
      environments. We conclude that human temperament is strongly influenced by more
      than 700 genes that modulate associative conditioning by molecular processes for
      synaptic plasticity and long-term memory.

PMID- 30279458
TI  - Connectomics of bipolar disorder: a critical review, and evidence for dynamic
      instabilities within interoceptive networks.
AB  - The notion that specific cognitive and emotional processes arise from
      functionally distinct brain regions has lately shifted toward a connectivity
      based approach that emphasizes the role of network-mediated integration across
      regions. The clinical neurosciences have likewise shifted from a predominantly
      lesion-based approach to a connectomic paradigm-framing disorders as diverse as
      stroke, schizophrenia (SCZ), and dementia as "dysconnection syndromes". Here we
      position bipolar disorder (BD) within this paradigm. We first summarise the
      disruptions in structural, functional and effective connectivity that have been
      documented in BD. Not surprisingly, these disturbances show a preferential impact
      on circuits that support emotional processes, cognitive control and executive
      functions. Those at high risk (HR) for BD also show patterns of connectivity that
      differ from both matched control populations and those with BD, and which may
      thus speak to neurobiological markers of both risk and resilience. We highlight
      research fields that aim to link brain network disturbances to the phenotype of
      BD, including the study of large-scale brain dynamics, the principles of network
      stability and control, and the study of interoception (the perception of
      physiological states). Together, these findings suggest that the affective
      dysregulation of BD arises from dynamic instabilities in interoceptive circuits
      which subsequently impact on fear circuitry and cognitive control systems. We
      describe the resulting disturbance as a "psychosis of interoception".

PMID- 30279460
TI  - Downregulation of autophagy by 12/15Lipoxygenase worsens the phenotype of an
      Alzheimer's disease mouse model with plaques, tangles, and memory impairments.
AB  - Among the different initiating events in Alzheimer's disease (AD) pathogenesis,
      oxidative stress and neuroinflammation are some of the most iimportant. In the
      central nervous system, the 12/15Lipoxygenase (12/15LO) enzyme is the source of
      potent pro-oxidants and inflammatory lipid mediators. Previous works showed that
      this pathway is up-regulated in AD brains and that its pharmacological targeting
      modulates the phenotype of transgenic mouse models of the disease. Here we
      investigate the effect of brain 12/15LO gene delivery on the AD-like phenotype of
      a mouse model with plaques, tangles and behavioral deficits, the 3xTg mice.
      Compared with controls, mice over-expressing 12/15LO manifested an exacerbation
      of spatial learning and memory impairments, which was associated with significant
      increase in Abeta formation and deposition, and accumulation of hyper
      phosphorylated insoluble tau secondary to a down-regulation of autophagy. In
      addition, the same mice manifested a worsening of neuroinflammation and synaptic
      pathology. Taken together our study supports the hypothesis that the 12/15LO
      enzymatic pathway by impairing neuronal autophagy plays a functional role in
      exacerbating AD-related neuropathologies and cognitive impairments. It provides
      further critical preclinical evidence to justify developing and testing new and
      selective 12/15LO inhibitors for AD treatment.

PMID- 30279459
TI  - Brain scans from 21,297 individuals reveal the genetic architecture of
      hippocampal subfield volumes.
AB  - The hippocampus is a heterogeneous structure, comprising histologically
      distinguishable subfields. These subfields are differentially involved in memory
      consolidation, spatial navigation and pattern separation, complex functions often
      impaired in individuals with brain disorders characterized by reduced hippocampal
      volume, including Alzheimer's disease (AD) and schizophrenia. Given the
      structural and functional heterogeneity of the hippocampal formation, we sought
      to characterize the subfields' genetic architecture. T1-weighted brain scans (n =
      21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in
      FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co
      varying for whole hippocampal volume. We further calculated the single-nucleotide
      polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic
      correlation with each other, with other structural brain features and with AD and
      schizophrenia. All outcome measures were corrected for age, sex and intracranial
      volume. We found 15 unique genome-wide significant loci across six subfields, of
      which eight had not been previously linked to the hippocampus. Top SNPs were
      mapped to genes associated with neuronal differentiation, locomotor behaviour,
      schizophrenia and AD. The volumes of all the subfields were estimated to be
      heritable (h2 from 0.14 to 0.27, all p < 1 * 10-16) and clustered together based
      on their genetic correlations compared with other structural brain features.
      There was also evidence of genetic overlap of subicular subfield volumes with
      schizophrenia. We conclude that hippocampal subfields have partly distinct
      genetic determinants associated with specific biological processes and traits.
      Taking into account this specificity may increase our understanding of
      hippocampal neurobiology and associated pathologies.

PMID- 30279461
TI  - Multisite de novo mutations in human offspring after paternal exposure to
      ionizing radiation.
AB  - A genome-wide evaluation of the effects of ionizing radiation on mutation
      induction in the mouse germline has identified multisite de novo mutations
      (MSDNs) as marker for previous exposure. Here we present the results of a small
      pilot study of whole genome sequencing in offspring of soldiers who served in
      radar units on weapon systems that were emitting high-frequency radiation. We
      found cases of exceptionally high MSDN rates as well as an increased mean in our
      cohort: While a MSDN mutation is detected in average in 1 out of 5 offspring of
      unexposed controls, we observed 12 MSDNs in altogether 18 offspring, including a
      family with 6 MSDNs in 3 offspring. Moreover, we found two translocations, also
      resulting from neighboring mutations. Our findings indicate that MSDNs might be
      suited in principle for the assessment of DNA damage from ionizing radiation also
      in humans. However, as exact person-related dose values in risk groups are
      usually not available, the interpretation of MSDNs in single families would
      benefit from larger molecular epidemiologic studies on this new biomarker.

PMID- 30279462
TI  - Development of multi-layered and multi-sensitive polymeric nanocontainers for
      cancer therapy: in vitro evaluation.
AB  - Nanoscale drug delivery systems represent a promising strategy to treat cancer
      and to overcome the side effects of chemotherapy. In particular, hollow polymeric
      nanocontainers have attracted great interest because of their structural and
      morphological advantages and the variety of polymers that can be used, allowing
      the synthesis of stimuli-responsive materials capable of responding to the
      biochemical alterations of the tumour microenvironment. Here are reported the
      synthesis, characterization and in vitro evaluation of a three-stimuli-sensitive
      hollow nanocontainer consisting of three different shells, each one sensitive to
      a specific tumoral stimulus: in order pH, temperature and reducing environment.
      To test its properties, daunorubicin was used as a model drug, for which the
      nanocontainers exhibited excellent encapsulation ability. The in vitro drug
      release behaviour was studied under different conditions, where the system proved
      capable of responding to the selected tumoral stimuli by releasing a larger
      amount of drug than in physiological environment. The hollow system itself showed
      negligible cytotoxicity but the loaded nanocontainers and free drug showed
      identical cytotoxicity and intracellular localization. Therefore, this
      formulation can be considered as a promising platform to develop an injectable
      delivery system capable of improving systematic toxicity without affecting or
      reducing the activity of the encapsulated drug.

PMID- 30279463
TI  - A High-Speed SSVEP-Based BCI Using Dry EEG Electrodes.
AB  - A high-speed steady-state visual evoked potentials (SSVEP)-based brain-computer
      interface (BCI) system using dry EEG electrodes was demonstrated in this study.
      The dry electrode was fabricated in our laboratory. It was designed as claw-like
      structure with a diameter of 14 mm, featuring 8 small fingers of 6 mm length and
      2 mm diameter. The structure and elasticity can help the fingers pass through the
      hair and contact the scalp when the electrode is placed on head. The electrode
      was capable of recording spontaneous EEG and evoked brain activities such as
      SSVEP with high signal-to-noise ratio. This study implemented a twelve-class
      SSVEP-based BCI system with eight electrodes embedded in a headband. Subjects
      also completed a comfort level questionnaire with the dry electrodes. Using a
      preprocessing algorithm of filter bank analysis (FBA) and a classification
      algorithm based on task-related component analysis (TRCA), the average
      classification accuracy of eleven participants was 93.2% using 1-second-long
      SSVEPs, leading to an average information transfer rate (ITR) of 92.35 bits/min.
      All subjects did not report obvious discomfort with the dry electrodes. This
      result represented the highest communication speed in the dry-electrode based BCI
      systems. The proposed system could provide a comfortable user experience and a
      stable control method for developing practical BCIs.

PMID- 30279464
TI  - Tensorial neutron tomography of three-dimensional magnetic vector fields in bulk
      materials.
AB  - Knowing the distribution of a magnetic field in bulk materials is important for
      understanding basic phenomena and developing functional magnetic materials.
      Microscopic imaging techniques employing X-rays, light, electrons, or scanning
      probe methods have been used to quantify magnetic fields within planar thin
      magnetic films in 2D or magnetic vector fields within comparable thin volumes in
      3D. Some years ago, neutron imaging has been demonstrated to be a unique tool to
      detect magnetic fields and magnetic domain structures within bulk materials.
      Here, we show how arbitrary magnetic vector fields within bulk materials can be
      visualized and quantified in 3D using a set of nine spin-polarized neutron
      imaging measurements and a novel tensorial multiplicative algebraic
      reconstruction technique (TMART). We first verify the method by measuring the
      known magnetic field of an electric coil and then investigate the unknown trapped
      magnetic flux within the type-I superconductor lead.

PMID- 30279465
TI  - Ecological conditions drive pace-of-life syndromes by shaping relationships
      between life history, physiology and behaviour in two populations of Eastern
      mosquitofish.
AB  - The pace-of-life syndrome (POLS) hypothesis predicts variation in behaviour and
      physiology among individuals to be associated with variation in life history.
      Thus, individuals on the "fast" end of POLS continuum grow faster, exhibit higher
      metabolism, are more risk prone, but die earlier than ones on the "slow" end.
      Empirical support is nevertheless mixed and modelling studies suggested POLS to
      vary along selection gradients. Therefore, including ecological variation when
      testing POLS is vastly needed to determine whether POLS is a fixed construct or
      the result of specific selection processes. Here, we tested POLS predictions
      between and within two fish populations originating from different ecological
      conditions. We observed opposing life histories between populations,
      characterized by differential investments into growth, fecundity, and functional
      morphology under identical laboratory conditions. A slower life history was, on
      average, associated with boldness (latency to emergence from a refuge), high
      activity (short freezing time and long distance travelled), and increased
      standard metabolism. Correlation structures among POLS traits were not consistent
      between populations, with the expression of POLS observed in the slow-growing but
      not in the fast-growing population. Our results suggest that POLS traits can
      evolve independently from one another and that their coevolution depends upon
      specific ecological processes.

PMID- 30279466
TI  - Early (<4 Weeks) Versus Standard (>= 4 Weeks) Endoscopically Centered Step-Up
      Interventions for Necrotizing Pancreatitis.
AB  - OBJECTIVES: Current guidelines for necrotizing pancreatitis (NP) recommend delay
      in drainage +/- necrosectomy until 4 or more weeks after initial presentation to
      allow collections to wall off. However, evidence of infection with clinical
      deterioration despite maximum support may mandate earlier (<4 weeks)
      intervention. There are concerns, but scant data regarding risk of complications
      and outcomes with early endoscopic intervention. Our aim was to compare the
      results of an endoscopic centered step-up approach to NP when initiated before
      versus 4 or more weeks. METHODS: All patients undergoing intervention for NP were
      managed using an endoscopically centered step-up approach, with transluminal
      drainage whenever feasible, +/-necrosectomy, and/or percutaneous catheter
      drainage as needed, with surgery only for failures. Interventions were
      categorized as early or standard based on timing of intervention (<4 weeks or >=
      4 weeks from onset of pancreatitis). Demographic data, indications and timing for
      interventions, number and type of intervention, mortality and morbidity (length
      of stay in hospital and ICU) and complications were compared. RESULTS: Of 305
      patients with collections associated with NP, 193 (63%) (median age-52 years)
      required intervention, performed by a step-up approach. Of the 193 patients, 76
      patients underwent early and 117 patients standard intervention. 144 (75%)
      interventions included endoscopic drainage +/- necrosectomy. As compared with
      standard intervention, early intervention was more often performed for infection
      (91% vs. 39%, p < 0.05), more associated with acute kidney injury (43% vs. 32%, p
      = 0.09), respiratory failure (41% vs. 22%, p = 0.005), and shock (13% vs. 4%, p <
      0.05). Organ failure improved significantly after intervention in both groups.
      There was a significant difference in mortality (13% vs. 4%, p = 0.02) and need
      for rescue open necrosectomy (7% vs. 1%, p = 0.03) between groups. Patients
      undergoing early intervention had increased median hospital (37 days vs. 26 days,
      p = 0.01) and ICU stay (median 2.5 days vs. 0 days, p = 0.001). There was no
      difference in complications. CONCLUSIONS: When using an endoscopically centered
      step-up strategy in necrotizing pancreatitis, early (<4 weeks) interventions were
      more often performed for infection and organ failure, with no increase in
      complications, similar improvement in organ failure, slightly increased need for
      surgery, and relatively low mortality. Early endoscopic drainage +/- necrosectomy
      should be considered when there is a strong indication for intervention.

PMID- 30279467
TI  - Personalized response prediction.

PMID- 30279468
TI  - Lymphocyte activation gene 3 (Lag3) expression is increased in prion infections
      but does not modify disease progression.
AB  - Prion diseases, Alzheimer's disease and Parkinson's disease (PD) are fatal
      degenerative disorders that share common neuropathological and biochemical
      features, including the aggregation of pathological protein conformers.
      Lymphocyte activation gene 3 (Lag3, also known as CD223) is a member of the
      immunoglobulin superfamily of receptors expressed on peripheral immune cells,
      microglia and neurons, which serves as a receptor for alpha-synuclein aggregates
      in PD. Here we examined the possible role of Lag3 in the pathogenesis of prion
      diseases. Through quantitative real-time PCR and RNA-sequencing, we found that
      the expression levels of Lag3 were relatively low in the adult mouse brains, yet
      its expression was increased after prion infection. However, we failed finding
      significant differences regarding the incubation time, PrPSc load,
      neurodegeneration, astrocyte and microglia reactions and inflammatory gene
      expression between the Lag3 knockout mice and wild-type littermate controls after
      prion infection. We conclude that loss of Lag3 has no significant influence on
      prion disease pathogenesis. Considering that Lag3 is an immune checkpoint
      receptor, our results suggest that immune checkpoint inhibition (an increasingly
      prevalent therapeutic modality against many types of cancer) might not exert
      positive or negative effects on the progression of prion diseases.

PMID- 30279469
TI  - A hierarchical anti-Hebbian network model for the formation of spatial cells in
      three-dimensional space.
AB  - Three-dimensional (3D) spatial cells in the mammalian hippocampal formation are
      believed to support the existence of 3D cognitive maps. Modeling studies are
      crucial to comprehend the neural principles governing the formation of these
      maps, yet to date very few have addressed this topic in 3D space. Here we present
      a hierarchical network model for the formation of 3D spatial cells using anti
      Hebbian network. Built on empirical data, the model accounts for the natural
      emergence of 3D place, border, and grid cells, as well as a new type of
      previously undescribed spatial cell type which we call plane cells. It further
      explains the plausible reason behind the place and grid-cell anisotropic coding
      that has been observed in rodents and the potential discrepancy with the
      predicted periodic coding during 3D volumetric navigation. Lastly, it provides
      evidence for the importance of unsupervised learning rules in guiding the
      formation of higher-dimensional cognitive maps.

PMID- 30279471
TI  - Homozygosity mapping provides supporting evidence of pathogenicity in recessive
      Mendelian disease.
AB  - PURPOSE: One of the greatest challenges currently facing those studying Mendelian
      disease is identifying the pathogenic variant from the long list produced by a
      next-generation sequencing test. We investigate the predictive ability of
      homozygosity mapping for identifying the regions likely to contain the causative
      variant. METHODS: We use 179 homozygous pathogenic variants from three
      independent cohorts to investigate the predictive power of homozygosity mapping.
      RESULTS: We demonstrate that homozygous pathogenic variants in our cohorts are
      disproportionately likely to be found within one of the largest regions of
      homozygosity: 80% of pathogenic variants are found in a homozygous region that is
      in the ten largest regions in a sample. The maximal predictive power is achieved
      in patients with <8% homozygosity and variants >3 Mb from a telomere; this gives
      an area under the curve (AUC) of 0.735 and results in 92% of the causative
      variants being in one of the ten largest homozygous regions. CONCLUSION: This
      predictive power can be used to prioritize the list of candidate variants in gene
      discovery studies. When classifying a homozygous variant the size and rank of the
      region of homozygosity in which the candidate variant is located can also be
      considered as supporting evidence for pathogenicity.

PMID- 30279472
TI  - Mutations at the hydrophobic core affect Hal3 trimer stability, reducing its Ppz1
      inhibitory capacity but not its PPCDC moonlighting function.
AB  - S. cerevisiae Hal3 (ScHal3) is a moonlighting protein that, is in its monomeric
      state, regulates the Ser/Thr protein phosphatase Ppz1, but also joins ScCab3 (and
      in some instances the Hal3 paralog Vhs3) to form an unusual heterotrimeric
      phosphopantothenoylcysteine decarboxylase (PPCDC) enzyme. PPCDC is required for
      CoA biosynthesis and in most eukaryotes is a homotrimeric complex with three
      identical catalytic sites at the trimer interfaces. However, in S. cerevisiae the
      heterotrimeric arrangement results in a single functional catalytic center.
      Importantly, the specific structural determinants that direct Hal3's oligomeric
      state and those required for Ppz1 inhibition remain largely unknown. We
      mutagenized residues in the predicted hydrophobic core of ScHal3 (L403-L405) and
      the plant Arabidopsis thaliana Hal3 (AtHal3, G115-L117) oligomers and
      characterized their properties as PPCDC components and, for ScHal3, also as Ppz1
      inhibitor. We found that in AtHal3 these changes do not affect trimerization or
      PPCDC function. Similarly, mutation of ScHal3 L403 has no effect. In contrast,
      ScHal3 L405E fails to form homotrimers, but retains the capacity to bind Cab3
      explaining its ability to rescue a hal3 vhs3 synthetically lethal mutation.
      Remarkably, the L405E mutation decreases Hal3's ability to interact with and to
      inhibit Ppz1, confirming the importance of the oligomer/monomer equilibrium in
      Hal3's Ppz1 regulating function.

PMID- 30279470
TI  - Correction: IQSEC2-related encephalopathy in males and females: a comparative
      study including 37 novel patients.
AB  - This Article was originally published under Nature Research's License to Publish,
      but has now been made available under a CC BY 4.0 license. The PDF and HTML
      versions of the Article have been modified accordingly.

PMID- 30279473
TI  - Genomic assemblies of newly sequenced Trypanosoma cruzi strains reveal new
      genomic expansion and greater complexity.
AB  - Chagas disease is a complex illness caused by the protozoan Trypanosoma cruzi
      displaying highly diverse clinical outcomes. In this sense, the genome sequence
      elucidation and comparison between strains may lead to disease understanding.
      Here, two new T. cruzi strains, have been sequenced, Y using Illumina and Bug2148
      using PacBio, assembled, analyzed and compared with the T. cruzi annotated
      genomes available to date. The assembly stats from the new sequences show
      effective improvement of T. cruzi genome over the actual ones. Such as, the
      largest contig assembled (1.3 Mb in Bug2148) in de novo attempts and the highest
      mean assembly coverage (71X for Y). Our analysis reveals a new genomic expansion
      and greater complexity for those multi-copy gene families related to infection
      process and disease development, such as Trans-sialidases, Mucins and Mucin
      Associated Surface Proteins, among others. On one side, we demonstrate that multi
      copy gene families are located near telomeric regions of the "chromosome-like"
      1.3 Mb contig assembled of Bug2148, where they likely suffer high evolutive
      pressure. On the other hand, we identified several strain-specific single copy
      genes that might help to understand the differences in infectivity and physiology
      among strains. In summary, our results indicate that T. cruzi has a complex
      genomic architecture that may have promoted its evolution.

PMID- 30279474
TI  - Polystyrene microplastics increase microbial release of marine Chromophoric
      Dissolved Organic Matter in microcosm experiments.
AB  - About 5 trillion plastic particles are present in our oceans, from the macro to
      the micro size. Like any other aquatic particulate, plastics and microplastics
      can create a micro-environment, within which microbial and chemical conditions
      differ significantly from the surrounding water. Despite the high and increasing
      abundance of microplastics in the ocean, their influence on the transformation
      and composition of marine organic matter is largely unknown. Chromophoric
      dissolved organic matter (CDOM) is the photo-reactive fraction of the marine
      dissolved organic matter (DOM) pool. Changes in CDOM quality and quantity have
      impacts on marine microbial dynamics and the underwater light environment. One
      major source of CDOM is produced by marine bacteria through their alteration of
      pre-existing DOM substrates. In a series of microcosm experiments in controlled
      marine conditions, we explored the impact of microplastics on the quality and
      quantity of microbial CDOM. In the presence of microplastics we observed an
      increased production of CDOM with changes in its molecular weight, which resulted
      from either an increased microbial CDOM production or an enhanced transformation
      of DOM from lower to higher molecular weight CDOM. Our results point to the
      possibility that marine microplastics act as localized hot spots for microbial
      activity, with the potential to influence marine carbon dynamics.

PMID- 30279475
TI  - Dysregulation of the endothelin pathway in lymphangioleiomyomatosis with no
      direct effect on cell proliferation and migration.
AB  - LAM is a rare low-grade metastasizing lung neoplasm. Inhibitors of mTOR improve
      clinical outcome of LAM patients by preventing loss of lung function.
      Nevertheless, other cell targets may be of interest for drug development.
      Therefore, we explored the potential role of EDN1 (endothelin) in LAM. We report
      an increased endothelin blood level in LAM patients as well as EDN1
      overexpression and EDN1 receptor downregulation in LAM-derived primary cells and
      in TSC2NEG cells mutated in TSC2. We evidenced EDN pathway dysregulation based on
      EDN1, EDNRA, EDNRB and ARRB1 mRNA expression in LAM-derived primary cells. We
      showed overexpression of EDN1 and ARRB1 mRNAs in TSC2NEG cells; these cells lost
      their ability to respond to stimulation by endothelin. We analyzed the effects of
      endothelin receptor antagonists alone or in combination with rapamycin, an mTOR
      inhibitor, on proliferation and migration of LAM cells. Rapamycin treatment of
      TSC2NEG cells significantly reduced cell proliferation or migration, while none
      of the tested inhibitors of EDN receptors impaired these functions. We showed
      that TSC2NEG cells have acquired a transformed phenotype as showed by their
      ability to grow as spheroids in semi-solid medium and that unlike endothelin
      receptors antagonists, rapamycin reduced anchorage-independent cell growth and
      prevented expansion of TSC2NEG spheroids.

PMID- 30279476
TI  - Riemerella anatipestifer AS87_RS09170 gene is responsible for biotin synthesis,
      bacterial morphology and virulence.
AB  - Riemerella anatipestifer is a bacterial pathogen responsible for major economic
      losses within the duck industry. Recent studies have revealed that biotin
      biosynthesis is critical for the bacterium's survival and virulence. We
      previously found that R. anatipestifer AS87_RS09170, a putative bioF gene, is
      important for bacterial virulence. In the present study, we characterized the
      AS87_RS09170 gene in R. anatipestifer strain Yb2. Sequence analysis indicated
      that the AS87_RS09170 gene is highly conserved among R. anatipestifer strains;
      the deduced protein harbored the conserved pyridoxal 5'-phosphate binding pocket
      of 8-amino-7-oxononanoate synthase. Western blot analysis demonstrated that the
      biotin-dependent enzyme was present in smaller quantities in the mutant strain
      Yb2DeltabioF compared to that of the wide-type strain Yb2, suggesting that the
      biotin biosynthesis was defective. The mutant strain Yb2DeltabioF displayed a
      decreased growth rate at the exponential phase in tryptic soy broth culture and
      in BeaverBeads Streptavidin treated tryptic soy broth culture, but recovered when
      biotin was supplemented. In addition, the mutant strain Yb2DeltabioF showed an
      enhanced biofilm formation, as well as increased adhesion and invasion capacities
      to duck embryo fibroblasts. Moreover, the mutant strain Yb2DeltabioF exhibited
      irregular shapes with budding vegetations and relatively thickened cell walls
      under scanning and transmission electron microscope observation, as well as a
      reduced capacity to establish systemic infection in a duck infection model. These
      results provide the first evidence that the R. anatipestifer AS87_RS09170 gene is
      responsible for biotin synthesis, bacterial morphology and virulence.

PMID- 30279477
TI  - Additive Manufactured and Topology Optimized Passive Shimming Elements for
      Permanent Magnetic Systems.
AB  - A method to create a highly homogeneous magnetic field by applying topology
      optimized, additively manufactured passive shimming elements is investigated. The
      topology optimization algorithm can calculate a suitable permanent and nonlinear
      soft magnetic design that fulfills the desired field properties. The permanent
      magnetic particles are bonded in a polyamide matrix and they are manufactured
      with a low-cost, end-user 3D printer. Stray field measurements and an inverse
      stray field simulation framework can determine printing and magnetization errors.
      The customized shimming elements are manufactured by a selective melting process
      which produces completely dense soft magnetic metal parts. The methodology is
      demonstrated on a simple example of two axial symmetric cylindrical magnets,
      which generates a high inhomogeneous magnetic field. In this case, the maximum
      magnetic field density is 25 mT and the the homogeneity can be increased by a
      factor of 35 or down to 60/00. Simulation and measurement results point out a
      good conformity. Additional topology optimizations of more than one shimming
      element layer show the opportunity to make the manufactured magnetic system even
      more homogeneous.

PMID- 30279478
TI  - Cationic domains in particle-forming and assembly-deficient HBV core antigens
      capture mammalian RNA that stimulates Th1-biased antibody responses by DNA
      vaccination.
AB  - The HBV core protein self-assembles into particles and encapsidates immune
      stimulatory bacterial RNA through a cationic COOH-terminal (C150-183) domain. To
      investigate if different cationic domains have an impact on the endogenous RNA
      binding of HBV-C antigens in mammalian cells, we developed a strep-tag (st) based
      expression/purification system for HBV-C/RNA antigens in vector-transfected HEK
      293 cells. We showed that HBV-stC but not HBV-stC149 particles (lacking the
      cationic domain) capture low amounts of mammalian RNA. Prevention of specific
      phosphorylation in cationic domains, either by exchanging the serine residues
      S155, S162 and S170 with alanines (HBV-stCAAA) or by exchanging the entire
      cationic domain with a HIV-tat48-57-like sequence (HBV-stC149tat) enhanced the
      encapsidation of RNA into mutant core particles. Particle-bound mammalian RNA
      functioned as TLR-7 ligand and induced a Th1-biased humoral immunity in B6 but
      not in TLR-7-/- mice by exogenous (protein) and endogenous (DNA) vaccines.
      Compared to core particles, binding of mammalian RNA to freely exposed cationic
      domains in assembly-deficient antigens was enhanced. However, RNA bound to non
      particulate antigens unleash its Th1-stimulating adjuvant activity by DNA- but
      not protein-based vaccination. Mammalian RNAs targeted by an endogenously
      expressed antigen thus function as a natural adjuvant in the host that
      facilitates priming of Th1-biased immune responses by DNA-based immunization.

PMID- 30279479
TI  - Vibrational control of selective bond cleavage in dissociative chemisorption of
      methanol on Cu(111).
AB  - Controlling product branching ratios in a chemical reaction represents a desired
      but difficult achievement in chemistry. In this work, we demonstrate the first
      example of altering the branching ratios in a multichannel reaction, i.e.,
      methanol dissociative chemisorption on Cu(111), via selectively exciting specific
      vibrational modes. To this end, we develop a globally accurate full-dimensional
      potential energy surface for the CH3OH/Cu(111) system and perform extensive
      vibrational state-selected molecular dynamics simulations. Our results show that
      O-H/C-H/C-O stretching vibrational excitations substantially enhance the
      respective bond scission processes, representing extraordinary bond selectivity.
      At a given total energy, the branching ratio of C-O/C-H dissociation can increase
      by as large as 100 times by exciting the C-O stretching mode which possesses an
      unprecedentedly strong vibrational efficacy on reactivity. This vibrational
      control can be realized by the well-designed experiment using a linearly
      polarized laser.

PMID- 30279481
TI  - Fast neural learning in dogs: A multimodal sensory fMRI study.
AB  - Dogs may follow their nose, but they learn associations to many types of sensory
      stimuli. Are some modalities learned better than others? We used awake fMRI in 19
      dogs over a series of three experiments to measure reward-related learning of
      visual, olfactory, and verbal stimuli. Neurobiological learning curves were
      generated for individual dogs by measuring activation over time within three
      regions of interest: the caudate nucleus, amygdala, and parietotemporal cortex.
      The learning curves showed that dogs formed stimulus-reward associations in as
      little as 22 trials. Consistent with neuroimaging studies of associative
      learning, the caudate showed a main effect for reward-related stimuli, but not a
      significant interaction with modality. However, there were significant
      differences in the time courses, suggesting that although multiple modalities are
      represented in the caudate, the rates of acquisition and habituation are modality
      dependent and are potentially gated by their salience in the amygdala. Visual and
      olfactory modalities resulted in the fastest learning, while verbal stimuli were
      least effective, suggesting that verbal commands may be the least efficient way
      to train dogs.

PMID- 30279480
TI  - Arc/Arg3.1 has an activity-regulated interaction with PICK1 that results in
      altered spatial dynamics.
AB  - Activity-regulated cytoskeleton-associated protein (Arc; also known as Arg3.1) is
      an immediate early gene product that is transcribed in dendritic spines and, to
      date, has been best characterized as a positive regulator of AMPAR endocytosis
      during long-term depression (LTD) through interaction with endocytic proteins.
      Here, we show that protein interacting with C terminal kinase 1 (PICK1), a
      protein known to bind to the GluA2 subunit of AMPARs and associated with AMPAR
      trafficking, was pulled-down from brain homogenates and synaptosomes when using
      Arc as immobilized bait. Fluctuation and FLIM-FRET-Phasor analysis revealed
      direct interaction between these proteins when co-expressed that was increased
      under depolarizing conditions in live cells. At the plasma membrane, Arc-mCherry
      oligomerization was found to be concentration dependent. Additionally, co
      expression of Arc-mCherry and EGFP-PICK1 followed by depolarizing conditions
      resulted in significant increases in the number and size of puncta containing
      both proteins. Furthermore, we identified the Arc binding region to be the first
      126 amino acids of the PICK1 BAR domain. Overall, our data support a novel
      interaction and model where PICK1 mediates Arc regulation of AMPARs particularly
      under depolarizing conditions.

PMID- 30279482
TI  - Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation
      and crotonylation in vivo.
AB  - Proteomic analysis of histones has shown that they are subject to a
      superabundance of acylations, which extend far beyond acetylation, to include:
      crotonylation, propionylation, butyrylation, malonylation, succinylation, beta
      hydroxybutyrylation and 2-hydroxyisobutyrylation. To date, much of the functional
      data has focussed on histone crotonylation which, similar to acetylation, has
      been associated with positive gene regulation and is added by the
      acyltransferase, p300. Although Sirtuins 1-3, along with HDAC3, have been shown
      to possess decrotonylase activity in vitro, there is relatively little known
      about the regulation of histone crotonylation in vivo. Here we show that Histone
      Deacetylase 1 and 2 (HDAC1/2), the catalytic core of numerous co-repressor
      complexes, are important histone decrotonylase enzymes. A ternary complex of
      HDAC1/CoREST1/LSD1 is able to hydrolyse both histone H3 Lys18-acetyl (H3K18ac)
      and H3 Lys18-crotonyl (H3K18cr) peptide substrates. Genetic deletion of HDAC1/2
      in ES cells increases global levels of histone crotonylation and causes an 85%
      reduction in total decrotonylase activity. Furthermore, we mapped H3K18cr in
      cells using ChIP-seq, with and without HDAC1/2, and observed increased levels of
      crotonylation, which largely overlaps with H3K18ac in the vicinity of
      transcriptional start sites. Collectively, our data indicate that HDAC1/2
      containing complexes are critical regulators of histone crotonylation in vivo.

PMID- 30279483
TI  - Angiogenic Properties of 'Leukocyte- and Platelet-Rich Fibrin'.
AB  - Leukocyte- and Platelet-Rich Fibrin (L-PRF) is an autologous platelet
      concentrate, consisting of a fibrin matrix enriched with platelets, leukocytes
      and a plethora of cytokines and growth factors. Since L-PRF is produced bedside
      from whole blood without the use of an anti-coagulant, it is becoming a popular
      adjuvant in regenerative medicine. While other types of platelet concentrates
      have been described to stimulate blood vessel formation, little is known about
      the angiogenic capacities of L-PRF. Therefore, this study aimed to fully
      characterize the angiogenic potential of L-PRF. With an antibody array, the
      growth factors released by L-PRF were determined and high levels of CXC chemokine
      receptor 2 (CXCR-2) ligands and epidermal growth factor (EGF) were found. L-PRF
      induced in vitro key steps of the angiogenic process: endothelial proliferation,
      migration and tube formation. In addition, we could clearly demonstrate that L
      PRF is able to induce blood vessel formation in vivo, the chorioallantoic
      membrane assay. In conclusion, we could demonstrate the angiogenic capacity of L
      PRF both in vitro and in vivo, underlying the clinical potential of this easy-to
      use platelet concentrate.

PMID- 30279484
TI  - Drug screening of biopsy-derived spheroids using a self-generated microfluidic
      concentration gradient.
AB  - Performing drug screening of tissue derived from cancer patient biopsies using
      physiologically relevant 3D tumour models presents challenges due to the limited
      amount of available cell material. Here, we present a microfluidic platform that
      enables drug screening of cancer cell-enriched multicellular spheroids derived
      from tumour biopsies, allowing extensive anticancer compound screening prior to
      treatment. This technology was validated using cell lines and then used to screen
      primary human prostate cancer cells, grown in 3D as a heterogeneous culture from
      biopsy-derived tissue. The technology enabled the formation of repeatable drug
      concentration gradients across an array of spheroids without external fluid
      actuation, delivering simultaneously a range of drug concentrations to multiple
      sized spheroids, as well as replicates for each concentration. As proof-of
      concept screening, spheroids were generated from two patient biopsies and a panel
      of standard-of-care compounds for prostate cancer were tested. Brightfield and
      fluorescence images were analysed to provide readouts of spheroid growth and
      health, as well as drug efficacy over time. Overall, this technology could prove
      a useful tool for personalised medicine and future drug development, with the
      potential to provide cost- and time-reduction in the healthcare delivery.

PMID- 30279486
TI  - A systems biology approach to explore the impact of maple tree dormancy release
      on sap variation and maple syrup quality.
AB  - Maple sap is a complex nutrient matrix collected during spring to produce maple
      syrup. The characteristics of sap change over the production period and its
      composition directly impacts syrup quality. This variability could in part be
      attributed to changes in tree metabolism following dormancy release, but little
      is known about these changes in deciduous trees. Therefore, understanding the
      variation in sap composition associated with dormancy release could help pinpoint
      the causes of some defects in maple syrup. In particular, a defect known as
      "buddy", is an increasing concern for the industry. This off-flavor appears
      around the time of bud break, hence its name. To investigate sap variation
      related to bud break and the buddy defect, we monitored sap variation with
      respect to a dormancy release index (Sbb) and syrup quality. First, we looked at
      variation in amino acid content during this period. We observed a shift in amino
      acid relative proportions associated with dormancy release and found that most of
      them increase rapidly near the point of bud break, correlating with changes in
      syrup quality. Second, we identified biological processes that respond to
      variation in maple sap by performing a competition assay using the barcoded
      Saccharomyces cerevisiae prototroph deletion collection. This untargeted approach
      revealed that the organic sulfur content may be responsible for the development
      of the buddy off-flavor, and that dormancy release is necessary for the
      appearance of the defect, but other factors such as microbial activity may also
      be contributing.

PMID- 30279485
TI  - RIP2 filament formation is required for NOD2 dependent NF-kappaB signalling.
AB  - Activation of the innate immune pattern recognition receptor NOD2 by the
      bacterial muramyl-dipeptide peptidoglycan fragment triggers recruitment of the
      downstream adaptor kinase RIP2, eventually leading to NF-kappaB activation and
      proinflammatory cytokine production. Here we show that full-length RIP2 can form
      long filaments mediated by its caspase recruitment domain (CARD), in common with
      other innate immune adaptor proteins. We further show that the NOD2 tandem CARDs
      bind to one end of the RIP2 CARD filament, suggesting a mechanism for polar
      filament nucleation by activated NOD2. We combine X-ray crystallography, solid
      state NMR and high-resolution cryo-electron microscopy to determine the atomic
      structure of the helical RIP2 CARD filament, which reveals the intermolecular
      interactions that stabilize the assembly. Using structure-guided mutagenesis, we
      demonstrate the importance of RIP2 polymerization for the activation of NF-kappaB
      signalling by NOD2. Our results could be of use to develop new pharmacological
      strategies to treat inflammatory diseases characterised by aberrant NOD2
      signalling.

PMID- 30279487
TI  - Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators.
AB  - In view of the role of sEH (soluble epoxide hydrolase) in hypertension, we have
      developed a rigorously validated pharmacophore model containing one HBA (Hydrogen
      Bond Acceptor), two HY (Hydrophobic) and one RA (Ring Aromatic) features. The
      model was used as a query to search the NCI (National Cancer Institute) and
      Maybridge database leading to retrieval of many compounds which were sorted on
      the basis of predicted activity, fit value and Lipinski's violation. The selected
      compounds were docked into the active site of enzyme soluble epoxide hydrolase.
      Potential interactions were observed between the features of the identified hits
      and the amino acids present in the docking site. The three selected compounds
      were subjected to in vitro evaluation using enzyme- based assay and the isolated
      rat aortic model followed by cytotoxicity studies. The results demonstrate that
      the identified compounds are potent, safe and novel soluble epoxide hydrolase
      inhibitors.

PMID- 30279488
TI  - A phage-based assay for the rapid, quantitative, and single CFU visualization of
      E. coli (ECOR #13) in drinking water.
AB  - Drinking water standards in the United States mandate a zero tolerance of generic
      E. coli in 100 mL of water. The presence of E. coli in drinking water indicates
      that favorable environmental conditions exist that could have resulted in
      pathogen contamination. Therefore, the rapid and specific enumeration of E. coli
      in contaminated drinking water is critical to mitigate significant risks to
      public health. To meet this challenge, we developed a bacteriophage-based
      membrane filtration assay that employs novel fusion reporter enzymes to fully
      quantify E. coli in less than half the time required for traditional enrichment
      assays. A luciferase and an alkaline phosphatase, both specifically engineered
      for increased enzymatic activity, were selected as reporter probes due to their
      strong signal, small size, and low background. The genes for the reporter enzymes
      were fused to genes for carbohydrate binding modules specific to cellulose. These
      constructs were then inserted into the E. coli-specific phage T7 which were used
      to infect E. coli trapped on a cellulose filter. During the infection, the
      reporters were expressed and released from the bacterial cells following the
      lytic infection cycle. The binding modules facilitated the immobilization of the
      reporter probes on the cellulose filter in proximity to the lysed cells.
      Following substrate addition, the location and quantification of E. coli cells
      could then be determined visually or using bioluminescence imaging for the
      alkaline phosphatase and luciferase reporters, respectively. As a result, a
      detection assay capable of quantitatively detecting E. coli in drinking water
      with similar results to established methods, but less than half the assay time
      was developed.

PMID- 30279489
TI  - Paradoxical positive association of serum adiponectin with all-cause mortality
      based on body composition in Japanese haemodialysis patients.
AB  - We have previously reported a paradoxical association of serum adiponectin with
      aortic calcification in haemodialysis patients. Because serum adiponectin is a
      nutritional marker, we examined the association between serum adiponectin and all
      cause mortality based on body composition in haemodialysis patients. The trunk
      and total body fat were determined. The patients were divided into two groups
      based on serum adiponectin levels. In Kaplan-Meier analysis, the higher
      adiponectin group showed higher mortality than the lower adiponectin group. Serum
      adiponectin showed an inverse correlation with the percentage of truncal fat,
      suggesting serum adiponectin as an inverse marker for adiposity in haemodialysis
      patients. However, even after adjustment for other factors, multivariate Cox
      proportional hazards analysis identified higher serum adiponectin as an
      independent factor positively associated with higher mortality in haemodialysis
      patients. This association held true even when the total fat mass was replaced
      with the percentage of truncal fat, and when total fat mass and percentage of
      truncal fat were simultaneously included. Thus, we found a paradoxical
      association of higher serum adiponectin with higher all-cause mortality in
      Japanese haemodialysis patients, independent of adiposity.

PMID- 30279490
TI  - Tailoring manganese oxide with atomic precision to increase surface site
      availability for oxygen reduction catalysis.
AB  - Controlling the structure of catalysts at the atomic level provides an
      opportunity to establish detailed understanding of the catalytic form-to-function
      and realize new, non-equilibrium catalytic structures. Here, advanced thin-film
      deposition is used to control the atomic structure of La2/3Sr1/3MnO3, a well
      known catalyst for the oxygen reduction reaction. The surface and sub-surface is
      customized, whereas the overall composition and d-electron configuration of the
      oxide is kept constant. Although the addition of SrMnO3 benefits the oxygen
      reduction reaction via electronic structure and conductivity improvements, SrMnO3
      can react with ambient air to reduce the surface site availability. Placing
      SrMnO3 in the sub-surface underneath a LaMnO3 overlayer allows the catalyst to
      maintain the surface site availability while benefiting from improved electronic
      effects. The results show the promise of advanced thin-film deposition for
      realizing atomically precise catalysts, in which the surface and sub-surface
      structure and stoichiometry are tailored for functionality, over controlling only
      bulk compositions.

PMID- 30279491
TI  - Hyperglycaemia-induced methylglyoxal accumulation potentiates VEGF resistance of
      diabetic monocytes through the aberrant activation of tyrosine phosphatase SHP
      2/SRC kinase signalling axis.
AB  - Diabetes mellitus (DM) is a major cardiovascular risk factor contributing to
      cardiovascular complications by inducing vascular cell dysfunction. Monocyte
      dysfunction could contribute to impaired arteriogenesis response in DM patients.
      DM monocytes show blunted chemotactic responses to arteriogenic stimuli, a
      condition termed as vascular endothelial growth factor (VEGF) resistance. We
      hypothesize that methylglyoxal (MG), a glucose metabolite, induces monocyte
      dysfunction and aimed to elucidate the underlying molecular mechanisms. Human
      monocytes exposed to MG or monocytes from DM patients or mice (db/db) showed VEGF
      resistance secondary to a pro-migratory phenotype. Mechanistically, DM conditions
      or MG exposure resulted in the upregulation of the expression of SHP-2
      phosphatase. This led to the enhanced activity of SHP-2 and aided an interaction
      with SRC kinase. SHP-2 dephosphorylated the inhibitory phosphorylation site of
      SRC leading to its abnormal activation and phosphorylation of cytoskeletal
      protein, paxillin. We demonstrated that MG-induced molecular changes could be
      reversed by pharmacological inhibitors of SHP-2 and SRC and by genetic depletion
      of SHP-2. Finally, a SHP-2 inhibitor completely reversed the dysfunction of
      monocytes isolated from DM patients and db/db mice. In conclusion, we identified
      SHP-2 as a hitherto unknown target for improving monocyte function in diabetes.
      This opens novel perspectives for treating diabetic complications associated with
      impaired monocyte function.

PMID- 30279494
TI  - The Role of p53 in Determining Mitochondrial Adaptations to Endurance Training in
      Skeletal Muscle.
AB  - p53 plays an important role in regulating mitochondrial homeostasis. However, it
      is unknown whether p53 is required for the physiological and mitochondrial
      adaptations with exercise training. Furthermore, it is also unknown whether
      impairments in the absence of p53 are a result of its loss in skeletal muscle, or
      a secondary effect due to its deletion in alternative tissues. Thus, we
      investigated the role of p53 in regulating mitochondria both basally, and under
      the influence of exercise, by subjecting C57Bl/6J whole-body (WB) and muscle
      specific p53 knockout (mKO) mice to a 6-week training program. Our results
      confirm that p53 is important for regulating mitochondrial content and function,
      as well as proteins within the autophagy and apoptosis pathways. Despite an
      increased proportion of phosphorylated p53 (Ser15) in the mitochondria, p53 is
      not required for training-induced adaptations in exercise capacity or
      mitochondrial content and function. In comparing mouse models, similar
      directional alterations were observed in basal and exercise-induced signaling
      modifications in WB and mKO mice, however the magnitude of change was less
      pronounced in the mKO mice. Our data suggest that p53 is required for basal
      mitochondrial maintenance in skeletal muscle, but is not required for the
      adaptive responses to exercise training.

PMID- 30279493
TI  - Correcting glucose-6-phosphate dehydrogenase deficiency with a small-molecule
      activator.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human
      genetic enzymopathies, is caused by over 160 different point mutations and
      contributes to the severity of many acute and chronic diseases associated with
      oxidative stress, including hemolytic anemia and bilirubin-induced neurological
      damage particularly in newborns. As no medications are available to treat G6PD
      deficiency, here we seek to identify a small molecule that corrects it.
      Crystallographic study and mutagenesis analysis identify the structural and
      functional defect of one common mutant (Canton, R459L). Using high-throughput
      screening, we subsequently identify AG1, a small molecule that increases the
      activity of the wild-type, the Canton mutant and several other common G6PD
      mutants. AG1 reduces oxidative stress in cells and zebrafish. Furthermore, AG1
      decreases chloroquine- or diamide-induced oxidative stress in human erythrocytes.
      Our study suggests that a pharmacological agent, of which AG1 may be a lead, will
      likely alleviate the challenges associated with G6PD deficiency.

PMID- 30279496
TI  - Non-alcoholic beverage and depression.

PMID- 30279495
TI  - Label-free Evaluation of Myocardial Infarct in Surgically Excised Ventricular
      Myocardium by Raman Spectroscopy.
AB  - Understanding the viability of the ischemic myocardial tissue is a critical issue
      in determining the appropriate surgical procedure for patients with chronic heart
      failure after myocardial infarction (MI). Conventional MI evaluation methods are;
      however, preoperatively performed and/or give an indirect information of
      myocardial viability such as shape, color, and blood flow. In this study, we
      realize the evaluation of MI in patients undergoing cardiac surgery by Raman
      spectroscopy under label-free conditions, which is based on intrinsic molecular
      constituents related to myocardial viability. We identify key signatures of Raman
      spectra for the evaluation of myocardial viability by evaluating the infarct
      border zone myocardium that were excised from five patients under surgical
      ventricular restoration. We also obtain a prediction model to differentiate the
      infarcted myocardium from the non-infarcted myocardium by applying partial least
      squares regression-discriminant analysis (PLS-DA) to the Raman spectra. Our
      prediction model enables identification of the infarcted tissues and the non
      infarcted tissues with sensitivities of 99.98% and 99.92%, respectively.
      Furthermore, the prediction model of the Raman images of the infarct border zone
      enabled us to visualize boundaries between these distinct regions. Our novel
      application of Raman spectroscopy to the human heart would be a useful means for
      the detection of myocardial viability during surgery.

PMID- 30279498
TI  - Advanced sulfide solid electrolyte by core-shell structural design.
AB  - Solid electrolyte is critical to next-generation solid-state lithium-ion
      batteries with high energy density and improved safety. Sulfide solid
      electrolytes show some unique properties, such as the high ionic conductivity and
      low mechanical stiffness. Here we show that the electrochemical stability window
      of sulfide electrolytes can be improved by controlling synthesis parameters and
      the consequent core-shell microstructural compositions. This results in a
      stability window of 0.7-3.1 V and quasi-stability window of up to 5 V for Li-Si-P
      S sulfide electrolytes with high Si composition in the shell, a window much
      larger than the previously predicted one of 1.7-2.1 V. Theoretical and
      computational work explains this improved voltage window in terms of volume
      constriction, which resists the decomposition accompanying expansion of the solid
      electrolyte. It is shown that in the limiting case of a core-shell morphology
      that imposes a constant volume constraint on the electrolyte, the stability
      window can be further opened up. Advanced strategies to design the next
      generation sulfide solid electrolytes are also discussed based on our
      understanding.

PMID- 30279497
TI  - Zebra finches identify individuals using vocal signatures unique to each call
      type.
AB  - Individual recognition is critical in social animal communication, but it has not
      been demonstrated for a complete vocal repertoire. Deciphering the nature of
      individual signatures across call types is necessary to understand how animals
      solve the problem of combining, in the same signal, information about identity
      and behavioral state. We show that distinct signatures differentiate zebra finch
      individuals for each call type. The distinctiveness of these signatures varies:
      contact calls bear strong individual signatures while calls used during
      aggressive encounters are less individualized. We propose that the costly
      solution of using multiple signatures evolved because of the limitations of the
      passive filtering properties of the birds' vocal organ for generating
      sufficiently individualized features. Thus, individual recognition requires the
      memorization of multiple signatures for the entire repertoire of conspecifics of
      interests. We show that zebra finches excel at these tasks.

PMID- 30279492
TI  - Megahertz serial crystallography.
AB  - The new European X-ray Free-Electron Laser is the first X-ray free-electron laser
      capable of delivering X-ray pulses with a megahertz inter-pulse spacing, more
      than four orders of magnitude higher than previously possible. However, to date,
      it has been unclear whether it would indeed be possible to measure high-quality
      diffraction data at megahertz pulse repetition rates. Here, we show that high
      quality structures can indeed be obtained using currently available operating
      conditions at the European XFEL. We present two complete data sets, one from the
      well-known model system lysozyme and the other from a so far unknown complex of a
      beta-lactamase from K. pneumoniae involved in antibiotic resistance. This result
      opens up megahertz serial femtosecond crystallography (SFX) as a tool for
      reliable structure determination, substrate screening and the efficient
      measurement of the evolution and dynamics of molecular structures using megahertz
      repetition rate pulses available at this new class of X-ray laser source.

PMID- 30279499
TI  - Lower extremity joint-level responses to pelvis perturbation during human
      walking.
AB  - The human leg joints play a major role in balance control during walking. They
      facilitate leg swing, and modulate the ground (re)action forces to prevent a
      fall. The aim of this study is to provide and explore data on perturbed human
      walking to gain a better understanding of balance recovery during walking through
      joint-level control. Healthy walking subjects randomly received anteroposterior
      and mediolateral pelvis perturbations at the instance of toe-off. The open-source
      modeling tool OpenSim was used to perform inverse kinematics and inverse dynamics
      analysis. We found hip joint involvement in accelerating and then halting leg
      swing, suggesting active preparation for foot placement. Additionally, responses
      in the stance leg's ankle and hip joints contribute to balance recovery by
      decreasing the body's velocity in the perturbation direction. Modulation also
      occurs in the plane perpendicular to the perturbation direction, to safeguard
      balance in both planes. Finally, the recorded muscle activity suggests both
      spinal and supra-spinal mediated contributions to balance recovery, scaling with
      perturbation magnitude and direction. The presented data provide a unique and
      multi-joint insight in the complexity of both frontal and sagittal plane balance
      control during human walking in terms of joint angles, moments, and power, as
      well as muscle EMG responses.

PMID- 30279500
TI  - The Chemokine CCL3 Regulates Myeloid Differentiation and Hematopoietic Stem Cell
      Numbers.
AB  - The chemokine CCL3 is frequently overexpressed in malignancies and overexpression
      leads to microenvironmental dysfunction. In murine models of chronic myelogenous
      leukemia (CML), CCL3 is critical for the maintenance of a leukemia stem cell
      population, and leukemia progression. With CCL3 implicated as a potentially
      viable therapeutic target, it is important to carefully characterize its role in
      normal hematopoietic homeostasis. CCL3-/- mice were used to evaluate the role of
      CCL3 in regulating hematopoietic stem and progenitor cell (HSPC) populations.
      CCL3-/- mice had loss of mature myeloid populations, while myeloid progenitors
      and HSPCs were increased, and microenvironmental populations were unchanged.
      These data show that CCL3 promotes myeloid lineage differentiation and the size
      of the HSPC pool independent of the supportive bone marrow microenvironment. Our
      results demonstrate a previously unrecognized role of CCL3 in the maintenance of
      homeostatic hematopoiesis that should be evaluated when targeting CCL3 signaling
      for the treatment of hematologic malignancy.

PMID- 30279502
TI  - Sin3A recruits Tet1 to the PAH1 domain via a highly conserved Sin3-Interaction
      Domain.
AB  - The Sin3A complex acts as a transcriptional hub, integrating the function of
      diverse transcription factors with histone modifying enzymes, notably, histone
      deacetylases (HDAC) 1 and 2. The Sin3A protein sits at the centre of the complex,
      mediating multiple simultaneous protein-protein interactions via its four paired
      amphipathic helix (PAH) domains (PAH1-4). The PAH domains contain a conserved
      four helical bundle, generating a hydrophobic cleft into which the single-helix
      of a Sin3-interaction domain (SID) is able to insert and bind with high affinity.
      Although they share a similar mode of interaction, the SIDs of different
      repressor proteins bind to only one of four potential PAH domains, due to the
      specific combination of hydrophobic residues at the interface. Here we report the
      identification of a highly conserved SID in the 5-methylcytosine dioxygenase,
      Tet1 (Tet1-SID), which interacts directly with the PAH1 domain of Sin3A. Using a
      combination of NMR spectroscopy and homology modelling we present a model of the
      PAH1/Tet1-SID complex, which binds in a Type-II orientation similar to Sap25.
      Mutagenesis of key residues show that the 11-amino acid Tet1-SID is necessary and
      sufficient for the interaction with Sin3A and is absolutely required for Tet1 to
      repress transcription in cells.

PMID- 30279503
TI  - Author Correction: Multilayer networks reveal the spatial structure of seed
      dispersal interactions across the Great Rift landscapes.
AB  - The original version of this Article contained Figshare links in the Code
      availability statement that were not functional. The correct Figshare links to
      MATLAB scripts and R code used in this study are
      https://doi.org/10.6084/m9.figshare.4955651 and
      https://doi.org/10.6084/m9.figshare.4836383, respectively. These errors have now
      been corrected in both the PDF and HTML versions of the Article.

PMID- 30279501
TI  - Cell cycle-resolved chromatin proteomics reveals the extent of mitotic
      preservation of the genomic regulatory landscape.
AB  - Regulation of transcription, replication, and cell division relies on
      differential protein binding to DNA and chromatin, yet it is unclear which
      regulatory components remain bound to compacted mitotic chromosomes. By utilizing
      the buoyant density of DNA-protein complexes after cross-linking, we here develop
      a mass spectrometry-based approach to quantify the chromatin-associated proteome
      at separate stages of the cell cycle. While epigenetic modifiers that promote
      transcription are lost from mitotic chromatin, repressive modifiers generally
      remain associated. Furthermore, while proteins involved in transcriptional
      elongation are evicted, most identified transcription factors are retained on
      mitotic chromatin to varying degrees, including core promoter binding proteins.
      This predicts conservation of the regulatory landscape on mitotic chromosomes,
      which we confirm by genome-wide measurements of chromatin accessibility. In
      summary, this work establishes an approach to study chromatin, provides a
      comprehensive catalog of chromatin changes during the cell cycle, and reveals the
      degree to which the genomic regulatory landscape is maintained through mitosis.

PMID- 30279504
TI  - Metabolic Alterations Associated with Atorvastatin/Fenofibric Acid Combination in
      Patients with Atherogenic Dyslipidaemia: A Randomized Trial for Comparison with
      Escalated-Dose Atorvastatin.
AB  - In the current study, the metabolic effects of atorvastatin dose escalation
      versus atorvastatin/fenofibric acid combination were compared using metabolomics
      analyses. Men and women with combined hyperlipidaemia were initially prescribed
      atorvastatin (10 mg, >=4 weeks). Patients who reached low-density lipoprotein
      cholesterol targets, but had triglyceride and high-density lipoprotein
      cholesterol levels >=150 mg/dL and <50 mg/dL, respectively, were randomized to
      receive atorvastatin 20 mg or atorvastatin 10 mg/fenofibric acid 135 mg for 12
      weeks. Metabolite profiling of serum was performed and changes in metabolites
      after drug treatment in the two groups were compared. Analysis was performed
      using patients' samples obtained before and after treatment. Of 89 screened
      patients, 37 who met the inclusion criteria were randomized, and 34 completed the
      study. Unlike that in the dose-escalation group, distinct clustering of both
      lipid and aqueous metabolites was observed in the combination group after
      treatment. Most lipid metabolites of acylglycerols and many of ceramides
      decreased, while many of sphingomyelins increased in the combination group.
      Atorvastatin dose escalation modestly decreased lysophosphatidylcholines;
      however, the effect of combination therapy was variable. Most aqueous metabolites
      decreased, while L-carnitine remarkably increased in the combination group. In
      conclusion, the atorvastatin/fenofibric acid combination induced distinct
      metabolite clustering. Our results provide comprehensive information regarding
      metabolic changes beyond conventional lipid profiles for this combination
      therapy.

PMID- 30279505
TI  - Defects, Dopants and Sodium Mobility in Na2MnSiO4.
AB  - Sodium manganese orthosilicate, Na2MnSiO4, is a promising positive electrode
      material in rechargeable sodium ion batteries. Atomistic scale simulations are
      used to study the defects, doping behaviour and sodium migration paths in
      Na2MnSiO4. The most favourable intrinsic defect type is the cation anti-site
      (0.44 eV/defect), in which, Na and Mn exchange their positions. The second most
      favourable defect energy process is found to be the Na Frenkel (1.60 eV/defect)
      indicating that Na diffusion is assisted by the formation of Na vacancies via the
      vacancy mechanism. Long range sodium paths via vacancy mechanism were constructed
      and it is confirmed that the lowest activation energy (0.81 eV) migration path is
      three dimensional with zig-zag pattern. Subvalent doping by Al on the Si site is
      energetically favourable suggesting that this defect engineering stratergy to
      increase the Na content in Na2MnSiO4 warrants experimental verification.

PMID- 30279506
TI  - Renoprotective effect of Zhenwu decoction against renal fibrosis by regulation of
      oxidative damage and energy metabolism disorder.
AB  - Zhenwu decoction (ZWD) is a promising traditional Chinese prescription against
      renal fibrosis, while its underlying mechanism remains unclear. Rat model of
      renal fibrosis were established and divided into control group, model group, ZWD
      treatment group and enalapril maleate treatment group. Metabolic profiles on
      serum samples from each group were acquired by using ultra performance liquid
      chromatography coupled with quadrupole time-of-flight high-resolution mass
      spectrometry. Metabolomics combined with molecular biology were comparatively
      conducted on samples of various groups. Fifteen potential biomarkers were
      identified and these biomarkers are mainly phospholipids and fatty acids. The
      results showed renal fibrosis was associated with oxidative damage and energy
      metabolism disorder. The results of histopathology, biochemistry and metabolomics
      demonstrated that ZWD exhibited an efficient renoprotective effect by alleviating
      oxidative stress, increasing energy metabolism and regulating fibrotic cytokines.
      This study provided scientific support for the research and development of new
      drugs from traditional Chinese medicine.

PMID- 30279507
TI  - Single Dose Administration of Taheebo Polyphenol Enhances Endurance Capacity in
      Mice.
AB  - Endurance capacity is important for maintenance of quality of life as well as
      performance of endurance athletes. In order to improve endurance, intake of
      nutritional supplements as well as exercise training is also important. Indeed,
      polyphenolic extracts from plants are known to improve endurance capacity via
      increase of fatty acid utilization, mitochondrial biogenesis or inhibition of
      oxidative stress. Taheebo, the extract obtained from inner bark of Tabebuia
      avellanedae has been reported to have beneficial effects for treatment of
      inflammation, oxidative stress and obesity. Here, we investigated the effects and
      mechanisms of polyphenol fraction of taheebo (taheebo polyphenol; TP) on
      endurance capacity of mice. Single dose administration of TP significantly
      increased running time until exhaustion. Acute TP administration increased blood
      glucose and muscle glycogen levels (p < 0.05) through alteration on expression
      level of genes involved with glycogen metabolism and gluconeogenesis.
      Furthermore, TP administration decreased exercise-induced increase of protein
      carbonyls in skeletal muscle. These results suggest that TP administration
      improve endurance capacity via up-regulation of skeletal muscle glycogen levels
      and maintenance of blood glucose by acceleration of gluconeogenesis as well as
      inhibition of exercise-induced oxidative stress. Single administration of TP also
      increased phosphorylation of AMP-activated protein kinase (AMPK) and gene
      expression level of sirtuin 1 (SIRT1) but did not change the marker of
      mitochondrial biogenesis.

PMID- 30279508
TI  - Locally-curved geometry generates bending cracks in the African elephant skin.
AB  - An intricate network of crevices adorns the skin surface of the African bush
      elephant, Loxodonta africana. These micrometre-wide channels enhance the
      effectiveness of thermal regulation (by water retention) as well as protection
      against parasites and intense solar radiation (by mud adherence). While the
      adaptive value of these structures is well established, their morphological
      characterisation and generative mechanism are unknown. Using microscopy, computed
      tomography and a custom physics-based lattice model, we show that African
      elephant skin channels are fractures of the animal brittle and desquamation
      deficient skin outermost layer. We suggest that the progressive thickening of the
      hyperkeratinised stratum corneum causes its fracture due to local bending
      mechanical stress in the troughs of a lattice of skin millimetric elevations. The
      African elephant skin channels are therefore generated by thickening of a brittle
      material on a locally-curved substrate rather than by a canonical tensile
      cracking process caused by frustrated shrinkage.

PMID- 30279510
TI  - The mapping of cancer incidence and mortality trends in the UK from 1980-2013
      reveals a potential for overdiagnosis.
AB  - The incidence of cancer in the United Kingdom has increased significantly over
      the last four decades. The aim of this study was to examine trends in UK cancer
      incidence and mortality by cancer site and assess the potential for
      overdiagnosis. Using Cancer Research UK incidence and mortality data for the
      period (1971-2014) we estimated percentage change in incidence and mortality
      rates and the incidence-mortality ratio (IMR) for cancers in which incidence had
      increased >50%. Incidence and mortality trend plots were used to assess the
      potential for overdiagnosis. Incidence rates increased from 67% (uterine) to 375%
      (melanoma). Change in mortality rates ranged from -69% (cervical) to +239%
      (liver). The greatest divergences occurred in uterine (IMR = 132), prostate (IMR
      = 9.6), oral (IMR = 9.8) and thyroid cancer (IMR = 5.3). Only in liver cancer did
      mortality track incidence (IMR = 1.1). For four cancer sites; uterine, prostate,
      oral and thyroid, incidence and mortality trends are suggestive of overdiagnosis.
      Trends in melanoma and kidney cancer suggest potential overdiagnosis and an
      underlying increase in true risk, whereas for cervical and breast cancer, trends
      may also reflect improvements in treatments or earlier diagnosis. A more detailed
      analysis is required to fully understand these patterns.

PMID- 30279511
TI  - Airway epithelial cells prime plasmacytoid dendritic cells to respond to
      pathogens via secretion of growth factors.
AB  - Plasmacytoid dendritic cells (PDCs) are critical for defense against respiratory
      viruses because of their propensity to secrete high levels of type I interferons
      (IFN). The functions of PDCs in the lung can be influenced by airway epithelial
      cells. We examined the effect of human primary bronchial epithelial cells (PBECs)
      on PDC functions by performing RNA-sequencing of PDCs after co-culture with air
      liquid interface differentiated PBECs. Functional analysis revealed that PDCs co
      cultured with PBECs displayed upregulation of type I IFN production and response
      genes. Upregulated transcripts included those encoding cytosolic sensors of DNA,
      ZBP-1,IRF-3, and NFkB as well as genes involved in amplification of the IFN
      response, such as IFNAR1, JAK/STAT, ISG15. In keeping with the RNA-seq data, we
      observe increased secretion of type I IFN and other cytokines in response to
      influenza in PDCs co-cultured with PBECs. The PDCs also primed Th1 responses in T
      cells. The enhanced response of PDCs co-cultured with PBECs was due to the action
      of growth factors, GMCSF, GCSF, and VEGF, which were secreted by PBECs on
      differentiation. These data highlight possible mechanisms to enhance the
      production of type-I IFN in the airways, which is critical for host defense
      against respiratory infections.

PMID- 30279509
TI  - Functional equivalence of genome sequencing analysis pipelines enables harmonized
      variant calling across human genetics projects.
AB  - Hundreds of thousands of human whole genome sequencing (WGS) datasets will be
      generated over the next few years. These data are more valuable in aggregate:
      joint analysis of genomes from many sources increases sample size and statistical
      power. A central challenge for joint analysis is that different WGS data
      processing pipelines cause substantial differences in variant calling in combined
      datasets, necessitating computationally expensive reprocessing. This approach is
      no longer tenable given the scale of current studies and data volumes. Here, we
      define WGS data processing standards that allow different groups to produce
      functionally equivalent (FE) results, yet still innovate on data processing
      pipelines. We present initial FE pipelines developed at five genome centers and
      show that they yield similar variant calling results and produce significantly
      less variability than sequencing replicates. This work alleviates a key technical
      bottleneck for genome aggregation and helps lay the foundation for community-wide
      human genetics studies.

PMID- 30279512
TI  - A dendritic cell-based systemic vaccine induces long-lived lung-resident memory
      Th17 cells and ameliorates pulmonary mycosis.
AB  - Tissue-resident memory T cells (TRMs) are a novel nonvascular memory T cell
      subset. Although CD8+ TRMs are well-characterized, CD4+ TRMs-especially lung
      resident memory Th17 cells-are still being defined. In this study, we
      characterized lung-resident memory Th17 cells (lung TRM17) and their role in
      protection against the highly virulent fungus Cryptococcus gattii. We found that
      intravenously transferred DCs preferentially migrated to lungs and attracted
      recipient DCs and led to the induction of long-lived Th17 cells expressing
      characteristic markers. This population could be clearly discriminated from
      circulating T cells by intravascular staining and was not depleted by the
      immunosuppressive agent FTY720. The C. gattii antigen re-stimulation assay
      revealed that vaccine-induced lung Th17 cells produced IL-17A but not IFNgamma.
      The DC vaccine significantly increased IL-17A production and suppressed fungal
      burden in the lungs and improved the survival of mice infected with C. gattii.
      This protective effect was significantly reduced in the IL-17A knockout (KO)
      mice, but not in the FTY720-treated mice. The protective effect also coincided
      with the activation of neutrophils and multinucleated giant cells, and these
      inflammatory responses were suppressed in the vaccinated IL-17A KO mice. Overall,
      these data demonstrated that the systemic DC vaccine induced lung TRM17, which
      played a substantial role in anti-fungal immunity.

PMID- 30279514
TI  - NLRC4 suppresses IL-17A-mediated neutrophil-dependent host defense through
      upregulation of IL-18 and induction of necroptosis during Gram-positive
      pneumonia.
AB  - Gram-positive pathogens, including Staphylococcus aureus, cause necrotizing
      pneumonia. The central feature of S. aureus pneumonia is toxin-induced
      necroptosis of immune and resident cells, which impedes host defense. However,
      the role of the NLRC4 in the lung following S. aureus infection remains elusive.
      Here, we demonstrate that S. aureus activates the NLRC4 to drive necroptosis and
      IL-18 production, which impaired IL-17A-dependent neutrophil-mediated host
      susceptibility. In particular, Nlrc4-/- mice exhibit reduced necroptosis,
      enhanced neutrophil influx into the lungs, decreased bacterial burden, and
      improved host survival. Loss of NLRC4 signaling in both hematopoietic and non
      hematopoietic cells contributes to the host protection against S. aureus
      pneumonia. Secretion of IL-17A by gammadelta T cells is essential for neutrophil
      recruitment into the lungs of Nlrc4-/- mice following infection. Moreover,
      treatment of wild-type mice with necroptosis inhibitors or genetic ablation of
      MLKL and IL-18 improves host defense against S. aureus infection, which is
      associated with increased IL-17A+gammadelta T cells and neutrophils. Taken
      together, these novel findings reveal that S. aureus activates the NLRC4 to
      dampen IL-17A-dependent neutrophil accumulation through induction of necroptosis
      and IL-18. Thus, modulating the function of the NLRC4 may be an attractive
      therapeutic approach for treating S. aureus infections.

PMID- 30279513
TI  - Resolvin D1 treatment on goblet cell mucin and immune responses in the chronic
      allergic eye disease (AED) model.
AB  - Severe, chronic eye allergy is an understudied, vision-threatening condition.
      Treatments remain limited. We used a mouse model of severe allergic eye disease
      (AED) to determine whether topical application of the pro-resolution mediator
      Resolvin D1 (RvD1) terminates the response. AED was induced by injection of
      ovalbumin (OVA) followed by topical challenge of OVA daily. RvD1 was applied
      topically prior to OVA. Clinical symptoms were scored. Eye washes were assayed
      for MUC5AC. After 7 days, eyes were removed and the number of goblet cells, T
      helper cell responses and presence of immune cells in draining lymph nodes and
      conjunctiva determined. Topical RvD1 treatment significantly reduced symptoms of
      AED. RvD1 did not alter the systemic type 2 immune response in the lymph nodes.
      AED increased the total amount of goblet cell mucin secretion, but not the number
      of goblet cells. RvD1 prevented this increase, but did not alter goblet cell
      number. Absolute numbers of CD4 + T cells, total CD11b + myeloid cells,
      eosinophils, neutrophils, and monocytes, but not macrophages increased in AED
      versus RvD1-treated mice. We conclude that topical application of RvD1 reduced
      the ocular allergic response by local actions in conjunctival immune response and
      a decrease in goblet cell mucin secretion.

PMID- 30279515
TI  - CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF
      beta-producing macrophages and T cells.
AB  - Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor
      PPAR-gamma and modulate metabolic and immune functions. Despite the worldwide use
      of CLA dietary supplementation, strong scientific evidence for its proposed
      beneficial actions are missing. We found that CLA-supplemented diet reduced
      mucosal damage and inflammatory infiltrate in the dextran sodium sulfate (DSS)
      induced colitis model. Conditional deletion of PPAR-gamma in macrophages from
      mice supplemented with CLA diet resulted in loss of this protective effect of
      CLA, suggesting a PPAR-gamma-dependent mechanism mediated by macrophages.
      However, CLA supplementation significantly worsened colorectal tumor formation
      induced by azoxymethane and DSS by inducing macrophage and T-cell-producing TGF
      beta via PPAR-gamma activation. Accordingly, either macrophage-specific deletion
      of PPAR-gamma or in vivo neutralization of latency-associated peptide (LAP, a
      membrane-bound TGF-beta)-expressing cells abrogated the protumorigenic effect of
      CLA. Thus, the anti-inflammatory properties of CLA are associated with prevention
      of colitis but also with development of colorectal cancer.

PMID- 30279516
TI  - NOX1-derived ROS drive the expression of Lipocalin-2 in colonic epithelial cells
      in inflammatory conditions.
AB  - Inflammatory bowel disease (IBD) is characterized by severe and recurrent
      inflammation of the gastrointestinal tract, associated with altered patterns of
      cytokine synthesis, excessive reactive oxygen species (ROS) production, and high
      levels of the innate immune protein, lipocalin-2 (LCN-2), in the mucosa. The
      major source of ROS in intestinal epithelial cells is the NADPH oxidase NOX1,
      which consists of the transmembrane proteins, NOX1 and p22PHOX, and the cytosolic
      proteins, NOXO1, NOXA1, and Rac1. Here, we investigated whether NOX1 activation
      and ROS production induced by key inflammatory cytokines in IBD causally affects
      LCN-2 production in colonic epithelial cells. We found that the combination of
      TNFalpha and IL-17 induced a dramatic upregulation of NOXO1 expression that was
      dependent on the activation of p38MAPK and JNK1/2, and resulted into an increase
      of NOX1 activity and ROS production. NOX1-derived ROS drive the expression of LCN
      2 by controlling the expression of IkappaBzeta, a master inducer of LCN-2.
      Furthermore, LCN-2 production and colon damage were decreased in NOX1-deficient
      mice during TNBS-induced colitis. Finally, analyses of biopsies from patients
      with Crohn's disease showed increased JNK1/2 activation, and NOXO1 and LCN-2
      expression. Therefore, NOX1 might play a key role in mucosal immunity and
      inflammation by controlling LCN-2 expression.

PMID- 30279517
TI  - Succinate receptor mediates intestinal inflammation and fibrosis.
AB  - Succinate, an intermediate of the tricarboxylic acid cycle, is accumulated in
      inflamed areas and its signaling through succinate receptor (SUCNR1) regulates
      immune function. We analyze SUCNR1 expression in the intestine of Crohn's disease
      patients and its role in murine intestinal inflammation and fibrosis. We show
      that both serum and intestinal succinate levels and SUCNR1 expression in
      intestinal surgical resections were higher in CD patients than in controls.
      SUCNR1 co-localized with CD86, CD206, and alpha-SMA+ cells in human intestine and
      we found a positive and significant correlation between SUCNR1 and alpha-SMA
      expression. In human isolated fibroblasts from CD patients SUCNR1 expression was
      higher than in those from controls and treatment with succinate increased SUCNR1
      expression, fibrotic markers and inflammatory cytokines through SUCNR1. This
      receptor modulated the expression of pro-inflammatory cytokines in resting murine
      macrophages, macrophage polarization and fibroblast activation and Sucnr1-/- mice
      were protected against both acute TNBS-colitis and intestinal fibrosis induced by
      the heterotopic transplant of colonic tissue. We demonstrate increased succinate
      levels in serum and SUCNR1 expression in intestinal tissue of CD patients and
      show a role for SUCNR1 in murine intestinal inflammation and fibrosis.

PMID- 30279518
TI  - Non-toxigenic Bacteroides fragilis (NTBF) administration reduces bacteria-driven
      chronic colitis and tumor development independent of polysaccharide A.
AB  - Polysaccharide A (PSA), an immunogenic capsular component of non-toxigenic
      Bacteroides fragilis (NTBF) strain NCTC 9343, is reported to promote mucosal
      immune development and suppress colitis. Contrastingly, enterotoxigenic
      Bacteroides fragilis (ETBF) is highly associated with inflammatory bowel disease
      (IBD) and colorectal cancer (CRC), rapidly inducing IL-17-dependent murine
      colitis and tumorigenesis. In specific-pathogen-free (SPF) C57BL/6 wild-type (WT)
      and multiple intestinal neoplasia (MinApc716+/-) mice, we show that sequential
      treatment of the NTBF strain, 9343, followed by the ETBF strain, 86-5443-2-2
      (86), diminished colitis and tumorigenesis. Mice treated simultaneously with 9343
      and 86 exhibited both severe colitis and tumorigenesis. Abrogated disease
      severity in sequentially treated mice was attributed to 9343 strain dominance and
      decreased IL-17A, but 86 colonization prior to or simultaneous with 9343
      mitigated the anti-inflammatory effect of 9343. Remarkably, 9343-mediated
      protection was independent of PSA, as sequentially treated mice receiving
      DeltaPSA 9343 exhibited similar protection. Further, SPF WT and Min mice
      colonized with PSA-competent or PSA-deficient 9343 exhibited similar IL-10, IL
      17, and IFN-gamma responses. Treatment of 86-colonized mice with 9343 failed to
      disrupt 86 pathogenesis. Our findings demonstrate that 9343 colonization,
      independent of PSA, offers prophylaxis against colitis-inducing 86 but may not be
      a valid therapy once colitis is established.

PMID- 30279519
TI  - Diagnostic value of plasma tryptophan and symmetric dimethylarginine levels for
      acute kidney injury among tacrolimus-treated kidney transplant patients by
      targeted metabolomics analysis.
AB  - Few literatures have evaluated the exact role of metabolomics in the
      identification process of potential biomarkers for acute kidney injury among the
      patients receiving renal transplantation. On top of this, the success of
      metabolomics in biomarker translation seems to lie in the robust quantitative
      method. As such, a single-center retrospective observational study was conducted
      enrolling 42 patients underwent renal transplantation with/without acute kidney
      injury, as well as 24 healthy volunteers, in Shanghai Changzheng Hospital. Plasma
      amino acid metabolic patterns for the participants were investigated by targeted
      UHPLC-MS/MS metabolic profiling. The most significant changes of the explored
      metabolites were related to the disturbance of tryptophan metabolism and arginine
      metabolism. Abnormal circulating tryptophan and symmetric dimethylarginine were
      identified to be potential biomarkers of acute kidney injury, combination of
      which showed a higher area under receiver-operator curve value (AUC = 0.901),
      improved sensitivity (0.889) and specificity (0.831) compared with creatinine
      only. Overall, these results revealed that targeted metabolomics analysis would
      be a potent and promising strategy for identification and pre-validation of
      biomarkers of acute kidney injury in renal transplantation patients.

PMID- 30279522
TI  - Discordant multi-decadal trend in the intensity of the Kuroshio along its path
      during 1993-2013.
AB  - The Kuroshio transports warm water in the Pacific poleward from the tropics and
      plays a crucial role in modulating surrounding climate. Based on independent data
      sets, we demonstrated that the Kuroshio weakened downstream east of Taiwan, but
      intensified upstream east of Luzon Island during 1993-2013. The surface velocity
      (volume transport) of the Kuroshio has decreased 12.5% (4~5%) off east Taiwan but
      increased 18% (8~18%) off east Luzon. The discordant upstream-downstream trend
      was attributable to changes in oceanic eddies and basin surface winds: greater
      (lesser) cyclonic eddies, lesser (greater) anticyclonic eddies, and positive
      (negative) tendency in the Pacific Basin wind curl contributed to a weakened
      (intensified) downstream (upstream) Kuroshio. The difference in water mass
      between the upstream and downstream Kuroshio was balanced by an anomalous
      eastward flow, the southern branch of the Subtropical Counter Current which was
      enhanced and evacuated the redundant water eastward into the Pacific.

PMID- 30279520
TI  - An African loss-of-function CACNA1C variant p.T1787M associated with a risk of
      ventricular fibrillation.
AB  - Calcium regulation plays a central role in cardiac function. Several variants in
      the calcium channel Cav1.2 have been implicated in arrhythmic syndromes. We
      screened patients with Brugada syndrome, short QT syndrome, early repolarisation
      syndrome, and idiopathic ventricular fibrillation to determine the frequency and
      pathogenicity of Cav1.2 variants. Cav1.2 related genes, CACNA1C, CACNB2 and
      CACNA2D1, were screened in 65 probands. Missense variants were introduced in the
      Cav1.2 alpha subunit plasmid by mutagenesis to assess their pathogenicity using
      patch clamp approaches. Six missense variants were identified in CACNA1C in five
      individuals. Five of them, A1648T, A1689T, G1795R, R1973Q, C1992F, showed no
      major alterations of the channel function. The sixth C-terminal variant,
      Cavalpha1c-T1787M, present mostly in the African population, was identified in
      two patients with resuscitated cardiac arrest. The first patient originated from
      Cameroon and the second was an inhabitant of La Reunion Island with idiopathic
      ventricular fibrillation originating from Purkinje tissues. Patch-clamp analysis
      revealed that Cavalpha1c-T1787M reduces the calcium and barium currents by
      increasing the auto-inhibition mediated by the C-terminal part and increases the
      voltage-dependent inhibition. We identified a loss-of-function variant,
      Cavalpha1c-T1787M, present in 0.8% of the African population, as a new risk
      factor for ventricular arrhythmia.

PMID- 30279521
TI  - Developmental transitions in amygdala PKC isoforms and AMPA receptor expression
      associated with threat memory in infant rats.
AB  - Although infants learn and remember, they rapidly forget, a phenomenon known as
      infantile amnesia. While myriad mechanisms impact this rapid forgetting, the
      molecular events supporting memory maintenance have yet to be explored. To
      explore memory mechanisms across development, we used amygdala-dependent odor
      shock conditioning and focused on mechanisms important in adult memory, the AMPA
      receptor subunits GluA1/2 and upstream protein kinases important for trafficking
      AMPAR, protein kinase M zeta (PKMzeta) and iota/lambda (PKCiota/lambda). We use
      odor-shock conditioning in infant rats because it is late-developing (postnatal
      day, PN10) and can be modulated by corticosterone during a sensitive period in
      early life. Our results show that memory-related molecules did not change in pups
      too young to learn threat (PN8) but were activated in pups old enough to learn
      (PN12), with increased PKMzeta-PKCiota/lambda and GluA2 similar to that observed
      in adult memory, but with an uncharacteristic decrease in GluA1. This molecular
      signature and behavioral avoidance of the conditioned odor was recapitulated in
      PN8 pups injected with CORT before conditioning to precociously induce learning.
      Blocking learning via CORT inhibition in older pups (PN12) blocked the expression
      of these molecules. PN16 pups showed a more adult-like molecular cascade of
      increased PKMzeta-PKCiota/lambda and GluA1-2. Finally, at all ages, zeta
      inhibitory peptide (ZIP) infusions into the amygdala 24 hr after conditioning
      blocked memory. Together, these results identify unique features of memory
      processes across early development: AMPAR subunits GluA1/2 and PKC isoform
      expression are differentially used, which may contribute to mechanisms of early
      life forgetting.

PMID- 30279523
TI  - The evolutionary conserved FOXJ1 target gene Fam183b is essential for motile
      cilia in Xenopus but dispensable for ciliary function in mice.
AB  - The transcription factor FOXJ1 is essential for the formation of motile cilia
      throughout the animal kingdom. Target genes therefore likely constitute an
      important part of the motile cilia program. Here, we report on the analysis of
      one of these targets, Fam183b, in Xenopus and mice. Fam183b encodes a protein
      with unknown function which is conserved from the green algae Chlamydomonas to
      humans. Fam183b is expressed in tissues harbouring motile cilia in both mouse and
      frog embryos. FAM183b protein localises to basal bodies of cilia in mIMCD3 cells
      and of multiciliated cells of the frog larval epidermis. In addition, FAM183b
      interacts with NUP93, which also localises to basal bodies. During frog
      embryogenesis, Fam183b was dispensable for laterality specification and brain
      development, but required for ciliogenesis and motility of epidermal
      multiciliated cells and nephrostomes, i.e. the embryonic kidney. Surprisingly,
      mice homozygous for a null allele did not display any defects indicative of
      disrupted motile ciliary function. The lack of a cilia phenotype in mouse and the
      limited requirements in frog contrast with high sequence conservation and the
      correlation of gene expression with the presence of motile cilia. This finding
      may be explained through compensatory mechanisms at sites where no defects were
      observed in our FAM183b-loss-of-function studies.

PMID- 30279525
TI  - Putting genetic variants to a fitness test.

PMID- 30279524
TI  - Microgravity induces autophagy via mitochondrial dysfunction in human Hodgkin's
      lymphoma cells.
AB  - Gravitational forces can impose physical stresses on the human body as it
      functions to maintain homeostasis. It has been reported that astronauts exposed
      to microgravity experience altered biological functions and many subsequent
      studies on the effects of microgravity have therefore been conducted. However,
      the anticancer mechanisms of simulated microgravity remain unclear. We previously
      showed that the proliferation of human Hodgkin's lymphoma (HL) cells was
      inhibited when these cells were cultured in time-averaged simulated microgravity
      (taSMG). In the present study, we investigated whether taSMG produced an
      anticancer effect. Exposure of human HL cells to taSMG for 2 days increased their
      reactive oxygen species (ROS) production and NADPH oxidase family gene
      expression, while mitochondrial mass, ATPase, ATP synthase, and intracellular ATP
      levels were decreased. Furthermore, human HL cells exposed to taSMG underwent
      autophagy via AMPK/Akt/mTOR and MAPK pathway modulation; such autophagy was
      inhibited by the ROS scavenger N-acetylcysteine (NAC). These results suggest an
      innovative therapeutic approach to HL that is markedly different from
      conventional chemotherapy and radiotherapy.

PMID- 30279526
TI  - LOTUS domain protein MARF1 binds CCR4-NOT deadenylase complex to post
      transcriptionally regulate gene expression in oocytes.
AB  - Post-transcriptional regulation of gene expression plays an essential role during
      oocyte maturation. Here we report that Drosophila MARF1 (Meiosis Regulator And
      mRNA Stability Factor 1), which consists of one RNA-recognition motif and six
      tandem LOTUS domains with unknown molecular function, is essential for oocyte
      maturation. When tethered to a reporter mRNA, MARF1 post-transcriptionally
      silences reporter expression by shortening reporter mRNA poly-A tail length and
      thereby reducing reporter protein level. This activity is mediated by the MARF1
      LOTUS domain, which binds the CCR4-NOT deadenylase complex. MARF1 binds cyclin A
      mRNA and shortens its poly-A tail to reduce Cyclin A protein level during oocyte
      maturation. This study identifies MARF1 as a regulator in oocyte maturation and
      defines the conserved LOTUS domain as a post-transcriptional effector domain that
      recruits CCR4-NOT deadenylase complex to shorten target mRNA poly-A tails and
      suppress their translation.

PMID- 30279528
TI  - Control of proline utilization by the Lrp-like regulator PutR in Caulobacter
      crescentus.
AB  - Cellular metabolism recently emerged as a central player modulating the bacterial
      cell cycle. The Alphaproteobacterium Caulobacter crescentus appears as one of the
      best models to study these connections, but its metabolism is still poorly
      characterized. Considering that it lives in oligotrophic environments, its
      capacity to use amino-acids is often critical for its growth. Here, we
      characterized the C. crescentus PutA bi-functional enzyme and showed that it is
      required for the utilization of proline as a carbon source. We also found that
      putA transcription and proline utilization by PutA are strictly dependent on the
      Lrp-like PutR activator. The activation of putA by PutR needs proline, which most
      likely acts as an effector molecule for PutR. Surprisingly, we also observed that
      an over-production of PutR leads to cell elongation in liquid medium containing
      proline, while it inhibits colony formation even in the absence of proline on
      solid medium. These cell division and growth defects were equally pronounced in a
      DeltaputA mutant background, indicating that PutR can play other roles beyond the
      control of proline catabolism. Altogether, these findings suggest that PutR might
      connect central metabolism with cell cycle processes.

PMID- 30279527
TI  - Chronic noise exposure exacerbates AD-like neuropathology in SAMP8 mice in
      relation to Wnt signaling in the PFC and hippocampus.
AB  - Non-genetic environmental hazards are thought to be associated with genetic
      susceptibility factors that increase Alzheimer's disease (AD) pathogenesis. Aging
      and chronic noise exposure have been considered important factors in the AD.
      Here, we investigated the impact of chronic noise exposure on the AD-like
      neuropathology in the senescence-accelerated prone mouse (SAMP8) and the
      underlying mechanisms of such effects. We examined the consequences of AD-like
      neuropathology in 3-month-old SAMP8 mice using low- and high-intensity noise
      exposure and 8-month-old SAMP8 mice as aging positive controls. Immunoblotting
      and immunohistochemistry were conducted to examine AD-like pathological changes
      and potential mechanisms. Chronic noise exposure led to progressive
      overproduction of Abeta and increased the hyperphosphorylation of tau at Ser396,
      Thr205, and Thr231 sites in the hippocampus and the prefrontal cortex (PFC) in
      young SAMP8 mice, similar to that observed in aging SAMP8 mice. Both noise
      exposure and aging could cause a significant downregulation in Wnt signaling
      expression. These findings demonstrate that chronic noise stress exacerbated AD
      like neuropathology, possibly by disrupting Wnt signaling and triggering aberrant
      tau hyperphosphorylation and Abeta in the PFC and hippocampus.

PMID- 30279529
TI  - Human and mouse albumin bind their respective neonatal Fc receptors differently.
AB  - Albumin has a serum half-life of three weeks in humans and is utilized to extend
      the serum persistence of drugs that are genetically fused or conjugated directly
      to albumin or albumin-binding molecules. Responsible for the long half-life is
      FcRn that protects albumin from intracellular degradation. An in-depth
      understanding of how FcRn binds albumin across species is of importance for
      design and evaluation of albumin-based therapeutics. Albumin consists of three
      homologous domains where domain I and domain III of human albumin are crucial for
      binding to human FcRn. Here, we show that swapping of two loops in domain I or
      the whole domain with the corresponding sequence in mouse albumin results in
      reduced binding to human FcRn. In contrast, humanizing domain I of mouse albumin
      improves binding. We reveal that domain I of mouse albumin plays a minor role in
      the interaction with the mouse and human receptors, as domain III on its own
      binds with similar affinity as full-length mouse albumin. Further, we show that
      P573 in domain III of mouse albumin is required for strong receptor binding. Our
      study highlights distinct differences in structural requirements for the
      interactions between mouse and human albumin with their respective receptor,
      which should be taken into consideration in design of albumin-based drugs and
      evaluation in mouse models.

PMID- 30279530
TI  - Identification of target genes for RNAi-mediated control of the Twospotted Spider
      Mite.
AB  - RNA interference (RNAi) is being developed for the management of pests that
      destroy crops. The twospotted Spider Mite (TSSM), Tetranychus urticae is a
      worldwide pest due to its unique physiological and behavioral characteristics
      including extraordinary ability to detoxify a wide range of pesticides and feed
      on many host plants. In this study, we conducted experiments to identify target
      genes that could be used for the development of RNAi-based methods to control
      TSSM. Leaf disc feeding assays revealed that knockdown in the expression genes
      coding for proteins involved in the biosynthesis and action of juvenile hormone
      (JH) and action of ecdysteroids [Methoprene-tolerant (Met), retinoid X receptor
      beta, farnesoic acid O-methyltransferase, and CREB-binding protein] caused 35-56%
      mortality. Transgenic tobacco plants expressing hairpin dsRNA targeting Met gene
      were generated and tested. About 48% mortality was observed in TSSM raised on
      transgenic tobacco plants expressing dsMet. These studies not only broaden our
      knowledge on understanding hormone action in TSSM but also identified target
      genes that could be used in RNAi-mediated control of TSSM.

PMID- 30279531
TI  - A genetic perspective on the relationship between eudaimonic -and hedonic well
      being.
AB  - Whether hedonism or eudaimonia are two distinguishable forms of well-being is a
      topic of ongoing debate. To shed light on the relation between the two, large
      scale available molecular genetic data were leveraged to gain more insight into
      the genetic architecture of the overlap between hedonic and eudaimonic well
      being. Hence, we conducted the first genome-wide association studies (GWAS) of
      eudaimonic well-being (N = ~108 K) and linked it to a GWAS of hedonic well-being
      (N = ~222 K). We identified the first two genome-wide significant independent
      loci for eudaimonic well-being and six independent loci for hedonic well-being.
      Joint analyses revealed a moderate phenotypic correlation (r = 0.53) and a high
      genetic correlation (rg = 0.78) between eudaimonic and hedonic well-being. This
      indicates that the genetic etiology of hedonic and eudaimonic well-being is
      substantially shared, with divergent (environmental) factors contributing to
      their phenotypic divergence. Loci regulating expression showed significant
      enrichment in the brain cortex, brain cerebellum, frontal cortex, as well as the
      cerebellar hemisphere for eudaimonic well-being. No significant enrichment for
      hedonic well-being is observed, although brain tissues were top ranked. Genetic
      correlations patterns with a range of positive and negative related phenotypes
      were largely similar for hedonic -and eudaimonic well-being. Our results reveal a
      large overlap between the genes that influence hedonism and the genes that
      influence eudaimonia.

PMID- 30279534
TI  - Autosomal dominant PKD gets an atomic map.

PMID- 30279532
TI  - Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac
      dysfunction.
AB  - Oxidative stress plays an important role in the pathogenesis of many disease
      states. In the heart, reactive oxygen species are linked with cardiac
      ischemia/reperfusion injury, hypertrophy, and heart failure. While this
      correlation between ROS and cardiac pathology has been observed in multiple
      models of heart failure, the independent role of hydrogen peroxide (H2O2) in
      vitro and in vivo is unclear, owing to a lack of tools for precise manipulation
      of intracellular redox state. Here we apply a chemogenetic system based on a
      yeast D-amino acid oxidase to show that chronic generation of H2O2 in the heart
      induces a dilated cardiomyopathy with significant systolic dysfunction. We
      anticipate that chemogenetic approaches will enable future studies of in vivo
      H2O2 signaling not only in the heart, but also in the many other organ systems
      where the relationship between redox events and physiology remains unclear.

PMID- 30279533
TI  - How phosphorylation influences E1 subunit pyruvate dehydrogenase: A computational
      study.
AB  - Pyruvate (PYR) dehydrogenase complex (PDC) is an enzymatic system that plays a
      crucial role in cellular metabolism as it controls the entry of carbon into the
      Krebs cycle. From a structural point of view, PDC is formed by three different
      subunits (E1, E2 and E3) capable of catalyzing the three reaction steps necessary
      for the full conversion of pyruvate to acetyl-CoA. Recent investigations pointed
      out the crucial role of this enzyme in the replication and survival of specific
      cancer cell lines, renewing the interest of the scientific community. Here, we
      report the results of our molecular dynamics studies on the mechanism by which
      posttranslational modifications, in particular the phosphorylation of three
      serine residues (Ser-264-alpha, Ser-271-alpha, and Ser-203-alpha), influence the
      enzymatic function of the protein. Our results support the hypothesis that the
      phosphorylation of Ser-264-alpha and Ser-271-alpha leads to (1) a perturbation of
      the catalytic site structure and dynamics and, especially in the case of Ser-264
      alpha, to (2) a reduction in the affinity of E1 for the substrate. Additionally,
      an analysis of the channels connecting the external environment with the
      catalytic site indicates that the inhibitory effect should not be due to the
      occlusion of the access/egress pathways to/from the active site.

PMID- 30279535
TI  - Genome-wide polygenic risk predictors for kidney disease.

PMID- 30279537
TI  - A magnetically recyclable photocatalyst with commendable dye degradation activity
      at ambient conditions.
AB  - An efficient, economical, environment-friendly and easy separable catalyst to
      treat environmental contaminants is an enduring attention in recent years due to
      their great potential for environmental protection and remediation. Here we have
      reported the excellent performance of polyaniline activated heterojunctured
      Ni0.5Zn0.5Fe2O4 catalyst to degrade azo dye in an aqueous solution at ambient
      condition. The catalyst was prepared via a simple facile polymerization
      procedure. The physicochemical properties and structure of the synthesized
      catalyst was confirmed by TGA, PXRD, FTIR, SEM, HRTEM, XPS, EDX, and DRS
      techniques. The developed catalyst has shown an accelerated degradation ability
      of an organic pollutant Orange ll Sodium salt azo dye about 100% for the dye
      concentration of 50 ppm within five minutes at ambient conditions with 1 g/l
      loading of catalyst. Simple facile synthesis, easy separation by an external
      magnet, good reusability and high degradation capability of the catalyst may
      promote the practical applications of the heterostructured catalyst at ambient
      condition for water remediation. The present study also explored possible
      credible charge transfer directions and mechanism of photocatalysis supported by
      trapping experiments and electrochemical impedance spectroscopy (EIS) measurement
      for the effective improvement of photocatalytic activity and enhancement of the
      visible light adsorption.

PMID- 30279536
TI  - Solar simulated light exposure alters metabolization and genotoxicity induced by
      benzo[a]pyrene in human skin.
AB  - Skin is a major barrier against external insults and is exposed to combinations
      of chemical and/or physical toxic agents. Co-exposure to the carcinogenic
      benzo[a]pyrene (B[a]P) and solar UV radiation is highly relevant in human health,
      especially in occupational safety. In vitro studies have suggested that UVB
      enhances B[a]P genotoxicity by activating the AhR pathway and overexpressing the
      cytochrome P450 enzymes responsible for the conversion of B[a]P into DNA damaging
      metabolites. Our present work involved more realistic conditions, namely ex vivo
      human skin explants and simulated sunlight (SSL) as a UV source. We found that
      topically applied B[a]P strongly induced expression of cutaneous cytochrome P450
      genes and formation of DNA adducts. However, gene induction was significantly
      reduced when B[a]P was combined with SSL. Consequently, formation of BPDE-adducts
      was also reduced when B[a]P was associated with SSL. Similar results were
      obtained with primary cultures of human keratinocytes. These results indicate
      that UV significantly impairs B[a]P metabolism, and decreases rather than
      increases immediate toxicity. However, it cannot be ruled out that decreased
      metabolism leads to accumulation of B[a]P and delayed genotoxicity.

PMID- 30279539
TI  - A Frequency Independent Framework for Synthesis of Programmable Non-reciprocal
      Networks.
AB  - Passive and linear nonreciprocal networks at microwave frequencies hold great
      promises in enabling new front-end architectures for wireless communication
      systems. Their non-reciprocity has been achieved by disrupting the time-reversal
      symmetry using various forms of biasing schemes, but only over a limited
      frequency range. Here we demonstrate a framework for synthesizing theoretically
      frequency-independent multi-port nonreciprocal networks. The framework is highly
      expandable and can have an arbitrary number of ports while simultaneously
      sustaining balanced performance and providing unprecedented programmability of
      non-reciprocity. A 4-port circulator based on such a framework is implemented and
      tested to produce a broadband nonreciprocal performance from 10 MHz to 900 MHz
      with a temporal switching effort at 23.8 MHz. With the combination of broad
      bandwidth, low temporal effort, and high programmability, the framework could
      inspire new ways of implementing multiple input multiple output (MIMO)
      communication systems for 5G.

PMID- 30279538
TI  - Chromatin architecture changes and DNA replication fork collapse are critical
      features in cryopreserved cells that are differentially controlled by
      cryoprotectants.
AB  - In this work, we shed new light on the highly debated issue of chromatin
      fragmentation in cryopreserved cells. Moreover, for the first time, we describe
      replicating cell-specific DNA damage and higher-order chromatin alterations after
      freezing and thawing. We identified DNA structural changes associated with the
      freeze-thaw process and correlated them with the viability of frozen and thawed
      cells. We simultaneously evaluated DNA defects and the higher-order chromatin
      structure of frozen and thawed cells with and without cryoprotectant treatment.
      We found that in replicating (S phase) cells, DNA was preferentially damaged by
      replication fork collapse, potentially leading to DNA double strand breaks
      (DSBs), which represent an important source of both genome instability and
      defects in epigenome maintenance. This induction of DNA defects by the freeze
      thaw process was not prevented by any cryoprotectant studied. Both in replicating
      and non-replicating cells, freezing and thawing altered the chromatin structure
      in a cryoprotectant-dependent manner. Interestingly, cells with condensed
      chromatin, which was strongly stimulated by dimethyl sulfoxide (DMSO) prior to
      freezing had the highest rate of survival after thawing. Our results will
      facilitate the design of compounds and procedures to decrease injury to
      cryopreserved cells.

PMID- 30279540
TI  - Pyrophosphate inhibits gluconeogenesis by restricting UDP-glucose formation in
      vivo.
AB  - Pyrophosphate (PPi) is produced by anabolic reactions and serves as an energy
      donor in the cytosol of plant cells; however, its accumulation to toxic levels
      disrupts several common biosynthetic pathways and is lethal. Before acquiring
      photosynthetic capacity, young seedlings must endure a short but critical
      heterotrophic period, during which they are nourished solely by sugar produced
      from seed reserves by the anabolic process of gluconeogenesis. Previously, we
      reported that excess PPi in H+-PPase-knockout fugu5 mutants of Arabidopsis
      thaliana severely compromised gluconeogenesis. However, the precise metabolic
      target of PPi inhibition in vivo remained elusive. Here, CE-TOF MS analyses of
      major metabolites characteristic of gluconeogenesis from seed lipids showed that
      the Glc6P;Fru6P level significantly increased and that Glc1P level was
      consistently somewhat higher in fugu5 compared to wild type. In contrast, the UDP
      Glc level decreased significantly in the mutants. Importantly, specific removal
      of PPi in fugu5, and thus in AVP1pro:IPP1 transgenic lines, restored the Glc1P
      and the Glc6P;Fru6P levels, increased the UDP-Glc level ~2.0-fold, and
      subsequently increased sucrose synthesis. Given the reversible nature of the
      Glc1P/UDP-Glc reaction, our results indicate that UGP-Glc pyrophosphorylase is
      the major target when excess PPi exerts inhibitory effects in vivo. To validate
      our findings, we analyzed metabolite responses using a mathematical theory called
      structural sensitivity analysis (SSA), in which the responses of concentrations
      in reaction systems to perturbations in enzyme activity are determined from the
      structure of the network alone. A comparison of our experimental data with the
      results of pure structural theory predicted the existence of unknown reactions as
      the necessary condition for the above metabolic profiles, and confirmed the above
      results. Our data support the notion that H+-PPase plays a pivotal role in
      cytosolic PPi homeostasis in plant cells. We propose that the combination of
      metabolomics and SSA is powerful when seeking to identify and predict metabolic
      targets in living cells.

PMID- 30279541
TI  - A Non-Targeted LC-MS Profiling Reveals Elevated Levels of Carnitine Precursors
      and Trimethylated Compounds in the Cord Plasma of Pre-Eclamptic Infants.
AB  - Preeclampsia (PE) is a complex pregnancy disorder. It is not extensively known
      how the metabolic alterations of PE women contribute to the metabolism of
      newborn. We applied liquid chromatography-mass spectrometry (LC-MS) based non
      targeted metabolomics to determine whether the metabolic profile of plasma from
      umbilical cord differs between infants born to PE and non-PE pregnancies in the
      FINNPEC study. Cord plasma was available from 42 newborns born from PE and 53
      from non-PE pregnancies. 133 molecular features differed between PE and non-PE
      newborns after correction for multiple testing. Decreased levels of 4-pyridoxic
      acid were observed in the cord plasma samples of PE newborns when compared to non
      PE newborns. Compounds representing following areas of metabolism were increased
      in the cord plasma of PE newborns: urea and creatine metabolism; carnitine
      biosynthesis and acylcarnitines; putrescine metabolites; tryptophan metabolism
      and phosphatidylcholines. To our knowledge, this study is the first one to apply
      LC-MS based metabolomics in cord plasma of PE newborns. We demonstrate that this
      strategy provides a global picture of the widespread metabolic alterations
      associated with PE and particularly the elevated levels of carnitine precursors
      and trimethylated compounds appear to be associated with PE at birth.

PMID- 30279542
TI  - Genome sequencing of Prototheca zopfii genotypes 1 and 2 provides evidence of a
      severe reduction in organellar genomes.
AB  - Prototheca zopfii (P. zopfii, class Trebouxiophyceae, order Chlorellales, family
      Chlorellaceae), a non-photosynthetic predominantly free-living unicellular alga,
      is one of the few pathogens belonging to the plant kingdom. This alga can affect
      many vertebrate hosts, sustaining systemic infections and diseases such as
      mastitis in cows. The aim of our work was to sequence and assemble the P. zopfii
      genotype 1 and genotype 2 mitochondrial and plastid genomes. Remarkably, the P.
      zopfii mitochondrial (38 Kb) and plastid (28 Kb) genomes are models of compaction
      and the smallest known in the Trebouxiophyceae. As expected, the P. zopfii
      genotype 1 and 2 plastid genomes lack all the genes involved in photosynthesis,
      but, surprisingly, they also lack those coding for RNA polymerases. Our results
      showed that plastid genes are actively transcribed in P. zopfii, which suggests
      that the missing RNA polymerases are substituted by nuclear-encoded paralogs. The
      simplified architecture and highly-reduced gene complement of the P. zopfii
      mitochondrial and plastid genomes are closer to those of P. stagnora and the
      achlorophyllous obligate parasite Helicosporidium than to those of P. wickerhamii
      or P. cutis. This similarity is also supported by maximum likelihood phylogenetic
      analyses inferences. Overall, the P. zopfii sequences reported here, which
      include nuclear genome drafts for both genotypes, will help provide both a deeper
      understanding of the evolution of Prototheca spp. and insights into the
      corresponding host/pathogen interactions.

PMID- 30279543
TI  - A novel system-level approach using RNA-sequencing data identifies miR-30-5p and
      miR-142a-5p as key regulators of apoptosis in myocardial infarction.
AB  - This study identified microRNAs involved in myocardial infarction (MI) through a
      novel system-level approach using RNA sequencing data in an MI mouse model. This
      approach involved the extraction of DEGs and DEmiRs from RNA-seq data in sham and
      MI samples and the subsequent selection of two miRNAs: miR-30-5p (family) and miR
      142a-5p, which were downregulated and upregulated in MI, respectively. Gene Set
      Enrichment Analysis (GSEA) using the predicted targets of the two miRNAs
      suggested that apoptosis is an essential gene ontology (GO)-associated term. In
      vitro functional assays using neonatal rat ventricular myocytes (NRVMs)
      demonstrated that miR-30-5p is anti-apoptotic and miR-142a-5p is pro-apoptotic.
      Luciferase assays showed that the apoptotic genes, Picalm and Skil, and the anti
      apoptotic genes, Ghr and Kitl, are direct targets of miR-30-5p and miR-142a-5p,
      respectively. siRNA studies verified the results of the luciferase assays for
      target validation. The results of the system-level high throughput approach
      identified a pair of functionally antagonistic miRNAs and their targets in MI.
      This study provides an in-depth analysis of the role of miRNAs in the
      pathogenesis of MI which could lead to the development of therapeutic tools. The
      system-level approach could be used to identify miRNAs involved in variety of
      other diseases.

PMID- 30279544
TI  - The intracellular proteome of African swine fever virus.
AB  - African swine fever (ASF) is a viral disease that affects members of the Suidae
      family such as African bush pigs, warthogs, but also domestic pigs, and wild
      boar. It is transmitted by direct contact of naive with infected animals, by soft
      ticks of the Ornithodoros genus, or indirectly by movement of infected animals,
      improper disposal of contaminated animal products or other sources related to
      human activity. The recent spread of ASF into Eastern and Central European
      countries is currently threatening the European pig industry. The situation is
      aggravated as to-date no efficient vaccine is available. African swine fever
      virus (ASFV) is a large enveloped ds DNA-virus encoding at least 150 open reading
      frames. Many of the deduced gene products have not been described, less
      functionally characterized. We have analysed ASFV protein expression in three
      susceptible mammalian cell lines representing a susceptible host (wild boar) and
      two non-susceptible species (human and green monkey) by mass spectrometry and
      provide first evidence for the expression of 23 so far uncharacterized ASFV ORFs.
      Expression levels of several newly identified ASFV proteins were remarkably high
      indicating importance in the viral replication cycle. Moreover, expression
      profiles of ASFV proteins in the three cell lines differed markedly.

PMID- 30279545
TI  - Contrast-enhanced ultrasound tractography for 3D vascular imaging of the
      prostate.
AB  - Diffusion tensor tractography (DTT) enables visualization of fiber trajectories
      in soft tissue using magnetic resonance imaging. DTT exploits the anisotropic
      nature of water diffusion in fibrous structures to identify diffusion pathways by
      generating streamlines based on the principal diffusion vector. Anomalies in
      these pathways can be linked to neural deficits. In a different field, contrast
      enhanced ultrasound is used to assess anomalies in blood flow with the aim of
      locating cancer-induced angiogenesis. Like water diffusion, blood flow and
      transport of contrast agents also shows a principal direction; however, this is
      now determined by the local vasculature. Here we show how the tractographic
      techniques developed for magnetic resonance imaging DTT can be translated to
      contrast-enhanced ultrasound, by first estimating contrast flow velocity fields
      from contrast-enhanced ultrasound acquisitions, and then applying tractography.
      We performed 4D in-vivo contrast-enhanced ultrasound of three human prostates,
      proving the feasibility of the proposed approach with clinically acquired
      datasets. By comparing the results to histopathology after prostate resection, we
      observed qualitative agreement between the contrast flow tracts and typical
      markers of cancer angiogenic microvasculature: higher densities and tortuous
      geometries in tumor areas. The method can be used in-vivo using a standard
      contrast-enhanced ultrasound protocol, opening up new possibilities in the area
      of vascular characterization for cancer diagnostics.

PMID- 30279547
TI  - Counterfactual Bell-State Analysis.
AB  - The Bell-state analysis to distinguish between the four maximally entangled Bell
      states requires the joint measurement on entangled particles. However, spatially
      separated parties cannot perform the joint measurement. In this paper, we present
      a counterfactual Bell-state analysis based on the chained quantum Zeno effect.
      This counterfactual analysis not only enables us to perform a complete Bell-state
      analysis, but also enables spatially separated parties to distinguish between the
      four Bell states without transmitting any physical particle over the channel.

PMID- 30279546
TI  - Authenticity and geographic origin of global honeys determined using carbon
      isotope ratios and trace elements.
AB  - Honey is the world's third most adulterated food. The addition of cane sugar or
      corn syrup and the mislabelling of geographic origin are common fraudulent
      practices in honey markets. This study examined 100 honey samples from Australia
      (mainland and Tasmania) along with 18 other countries covering Africa, Asia,
      Europe, North America and Oceania. Carbon isotopic analyses of honey and protein
      showed that 27% of commercial honey samples tested were of questionable
      authenticity. The remaining 69 authentic samples were subject to trace element
      analysis for geographic determination. One-way ANOVA analysis showed a
      statistical difference (p < 0.05) in trace element concentrations of honey from
      Australian regions and different continents. Principal component analysis (PCA)
      and canonical discriminant analysis (CDA) coupled with C5.0 classification
      modelling of honey carbon isotopes and trace element concentrations showed
      distinct clusters according to their geographic origin. The C5.0 model revealed
      trace elements Sr, P, Mn and K can be used to differentiate honey according to
      its geographic origin. The findings show the common and prevalent issues of honey
      authenticity and the mislabelling of its geographic origin can be identified
      using a combination of stable carbon isotopes and trace element concentrations.

PMID- 30279548
TI  - NMR spectroscopy enables simultaneous quantification of carbohydrates for
      diagnosis of intestinal and gastric permeability.
AB  - Increased intestinal or gastric permeability is one of the major hallmarks of
      liver cirrhosis. The current gold standard for diagnosis of aberrant gut
      permeability due to disease is the triple-sugar test, where carbohydrates are
      orally administered and urinary excretion is measured. Hereby, elevated lactulose
      levels indicate intestinal permeability, whereas increased sucrose levels reveal
      gastric permeability. However, reliable detection and quantification of these
      sugars in a complex biological fluid still remains challenging due to interfering
      substances. Here we used Nuclear Magnetic Resonance (NMR) spectroscopy with a
      simple and fast protocol, without any additional sample extraction steps, for
      straight-forward simultaneous quantification of sugars in urine in order to
      detect increased intestinal and gastric permeability. Collected urine samples
      were diluted in buffer and one- and two-dimensional proton spectra were recorded
      in order to reveal carbohydrate concentrations in individual urine samples
      containing mannitol, sucrose and/or lactulose. Overall, this article presents a
      fast and robust method for simultaneous quantification of different sugars down
      to low micro-molar concentrations for research studies and can be further
      extended for clinical studies with automation of the quantification process.

PMID- 30279549
TI  - Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up
      regulates Survivin/NF-kappaB/p65 Expression.
AB  - This study is aimed to investigate whether simvastatin induces cardiomyocytes
      survival signaling in endotoxin (lipopolysaccharide, LSP)-induced myocardial
      injury, and if so, further to determine a role of survivin in simvastatin-anti
      apoptotic effect. Wistar rats were pretreated with simvastatin (10-40 mg/kg po)
      before a single non-lethal dose of LPS. In myocardial tissue, LPS induced
      structural disorganization of myofibrils with significant inflammatory infiltrate
      (cardiac damage score, CDS = 3.87 +/- 0.51, p < 0.05), whereas simvastatin dose
      dependently abolished structural changes induced by LPS (p < 0.01). Simvastatin
      in 20 mg/kg and 40 mg/kg pretreatment, dose dependently, attenuated myocardial
      apoptosis determined as apoptotic index (28.8 +/- 4.5% and 18.9 +/- 3.5, p <
      0.05), decreased cleaved caspase-3 expression (32.1 +/- 5.8%, p < 0.01), along
      with significant Bcl-xL expression in the simvastatin groups (p < 0.01).
      Interestingly, in the simvastatin groups were determined significantly increased
      expression of survivin (p < 0.01), but in negative correlation with cleaved
      caspase-3 and apoptotic indices (p < 0.01). Simvastatin has a cardioprotective
      effects against LPS induced apoptosis. The effect may be mediated by up
      regulation of survivin via activation of NF-kappaB, which leads to reduced
      activation of caspase-3 and consequent apoptosis of cardiomyocytes in
      experimental sepsis.

PMID- 30279550
TI  - Atorvastatin provides a new lipidome improving early regeneration after partial
      hepatectomy in osteopontin deficient mice.
AB  - Osteopontin (OPN), a multifunctional cytokine that controls liver glycerolipid
      metabolism, is involved in activation and proliferation of several liver cell
      types during regeneration, a condition of high metabolic demands. Here we
      investigated the role of OPN in modulating the liver lipidome during regeneration
      after partial-hepatectomy (PH) and the impact that atorvastatin treatment has
      over regeneration in OPN knockout (KO) mice. The results showed that OPN
      deficiency leads to remodeling of phosphatidylcholine and triacylglycerol (TG)
      species primarily during the first 24 h after PH, with minimal effects on
      regeneration. Changes in the quiescent liver lipidome in OPN-KO mice included TG
      enrichment with linoleic acid and were associated with higher lysosome TG
      hydrolase activity that maintained 24 h after PH but increased in WT mice. OPN-KO
      mice showed increased beta-oxidation 24 h after PH with less body weight loss. In
      OPN-KO mice, atorvastatin treatment induced changes in the lipidome 24 h after PH
      and improved liver regeneration while no effect was observed 48 h post-PH. These
      results suggest that increased dietary-lipid uptake in OPN-KO mice provides the
      metabolic precursors required for regeneration 24 h and 48 h after PH. However,
      atorvastatin treatment offers a new metabolic program that improves early
      regeneration when OPN is deficient.

PMID- 30279551
TI  - Spider silk proteome provides insight into the structural characterization of
      Nephila clavipes flagelliform spidroin.
AB  - The capture spiral of web from N. clavipes spider consists of a single type of
      spidroin - the flagelliform silk protein, a natural material representing a
      combination of strength and high elasticity. Flagelliform spider silk is the most
      extensible silk fibre produced by orb weaver spiders and the structure of this
      remarkable material is still largely unknown. In the present study we used a
      proteomic approach to elucidate the complete sequence and the post-translational
      modifications of flagelliform silk proteins. The long sequence of flagelliform
      silk protein presents 45 hydroxylated proline residues, which may contribute to
      explain the mechanoelastic property of these fibres, since they are located in
      the GPGGX motif. The 3D-structure of the protein was modelled considering the
      three domains together, i.e., the N- and C-terminal non-repetitive domains, and
      the central repetitive domain. In the resulting molecular model there is a
      predominance of random structures in the solid fibres of the silk protein. The N
      terminal domain is composed of three alpha-helices and the C-terminal domain is
      composed of one small helical section. Proteomic data reported herein may be
      relevant for the development of novel approaches for the synthetic or recombinant
      production of novel silk-based spider polymers.

PMID- 30279552
TI  - Robustness of Voltage-induced Magnetocapacitance.
AB  - One of the most important achievements in the field of spintronics is the
      development of magnetic tunnel junctions (MTJs). MTJs exhibit a large tunneling
      magnetoresistance (TMR). However, TMR is strongly dependent on biasing voltage,
      generally, decreasing with applying bias. The rapid decay of TMR was a major
      deficiency of MTJs. Here we report a new phenomenon at room temperature, in which
      the tunneling magnetocapacitance (TMC) increases with biasing voltage in an MTJ
      system based on Co40Fe40B20/MgO/Co40Fe40B20. We have observed a maximum TMC value
      of 102% under appropriate biasing, which is the largest voltage-induced TMC
      effect ever reported for MTJs. We have found excellent agreement between theory
      and experiment for the bipolar biasing regions using Debye-Frohlich model
      combined with quartic barrier approximation and spin-dependent drift-diffusion
      model. Based on our calculation, we predict that the voltage-induced TMC ratio
      could reach 1100% in MTJs with a corresponding TMR value of 604%. Our work has
      provided a new understanding on the voltage-induced AC spin-dependent transport
      in MTJs. The results reported here may open a novel pathway for spintronics
      applications, e.g., non-volatile memories and spin logic circuits.

PMID- 30279553
TI  - Arrowtail RNA for Ligand Display on Ginger Exosome-like Nanovesicles to Systemic
      Deliver siRNA for Cancer Suppression.
AB  - Exosomes have shown increasing potential as delivery vesicles for therapy, but
      challenges like cost/yield, drug payload, and targeting specificity still exist.
      Plant derived exosome-like nanoparticles have been reported as a promising
      substitution and exhibit biocompatibility through oral, intranasal
      administration; however, systemic delivery of siRNA by exosome-like nanoparticles
      directly isolated from plants has not been reported. Recently, we reported the
      control of RNA orientation to decorate human derived exosome with cell targeting
      ligands for specific delivery of siRNA to tumors. Here, we expand to the
      application of arrowtail RNA nanoparticles for displaying ligands on ginger
      derived exosome-like nanovesicles (GDENs) for siRNA delivery and tumor inhibition
      through IV administration. Cushion ultracentrifugation coupled with equilibrium
      density gradient ultracentrifugation were used for purifying GDENs that displayed
      size, density, and morphology similar to human derived exosomes. Folic acid (FA),
      as a ligand, was displayed on the surface of GDENs for targeted delivery of
      survivin siRNA to KB cancer models. In vitro gene knockdown efficacy by FA
      3WJ/GDENs/siRNA complex was comparable to transfection. We observed inhibition of
      tumor growth on a xenograft model by intravenous administration, which reveals
      the potential of GDENs as an economic delivery system for siRNA.

PMID- 30279554
TI  - Development of a deep residual learning algorithm to screen for glaucoma from
      fundus photography.
AB  - The Purpose of the study was to develop a deep residual learning algorithm to
      screen for glaucoma from fundus photography and measure its diagnostic
      performance compared to Residents in Ophthalmology. A training dataset consisted
      of 1,364 color fundus photographs with glaucomatous indications and 1,768 color
      fundus photographs without glaucomatous features. A testing dataset consisted of
      60 eyes of 60 glaucoma patients and 50 eyes of 50 normal subjects. Using the
      training dataset, a deep learning algorithm known as Deep Residual Learning for
      Image Recognition (ResNet) was developed to discriminate glaucoma, and its
      diagnostic accuracy was validated in the testing dataset, using the area under
      the receiver operating characteristic curve (AROC). The Deep Residual Learning
      for Image Recognition was constructed using the training dataset and validated
      using the testing dataset. The presence of glaucoma in the testing dataset was
      also confirmed by three Residents in Ophthalmology. The deep learning algorithm
      achieved significantly higher diagnostic performance compared to Residents in
      Ophthalmology; with ResNet, the AROC from all testing data was 96.5 (95%
      confidence interval [CI]: 93.5 to 99.6)% while the AROCs obtained by the three
      Residents were between 72.6% and 91.2%.

PMID- 30279555
TI  - Comparative study of substrate free and amniotic membrane scaffolds for
      cultivation of limbal epithelial sheet.
AB  - Transplantation of cultivated limbal epithelial transplantation has been proven
      to restore the corneal surface in limbal stem cell deficiency (LSCD). Here we
      comparatively investigated the optimized conditions and the efficiency of limbal
      epithelial sheet growth in three media conditions as well as with substrate free
      (transwell), human amniotic membrane (HAM) sutured onto transwell inserts
      (HAMTW), and HAM slide scaffold (HAMS). Outcomes evaluated were outgrowth sheet
      size from limbal explants, expression of stem/progenitor cell markers p63alpha,
      ABCG2 and CK15, and colony formation efficiency (CFE). Additionally, limbal
      epithelial sheets on HAMS were transplanted into corneas of LSCD rabbit models.
      Limbal epithelial sheets with 5% human AB serum showed the greatest increase in
      ABCG2 efflux activity (JC1low), p63alpha expression, and CFE compared in both
      conditions without HAM and with HAM, respectively. The outgrowth sheet size, cell
      yield, and Ki67 expression were increased in limbal epithelial sheets on HAMS
      compared to transwell and HAMTW. ABCG2 efflux activity, p63alpha and CK15
      expressions, and CFE were also increased in limbal epithelial sheets on HAMS as
      well. In corneas of transplanted rabbit LSCD models, p63alpha expressions were
      noted in the basal layers and CK12 expressions were observed in superficial
      layers. Cultivation of limbal epithelial sheet on HAMS with xeno-free medium
      enhances the growth and stemness of limbal epithelial sheets.

PMID- 30279557
TI  - Author Correction: Active neutron and gamma-ray imaging of highly enriched
      uranium for treaty verification.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30279556
TI  - Analysis of the antimicrobial mechanism of porcine beta defensin 2 against E.
      coli by electron microscopy and differentially expressed genes.
AB  - Porcine beta defensin 2 (pBD2) is a cationic antimicrobial peptide with broad
      spectrum antibacterial activity, which makes it a potential alternative to
      antibiotics to prevent and cure diseases of pigs. However, development of pBD2 as
      an effective antibiotic agent requires molecular understanding of its functional
      mechanism against pathogens. In this study, we investigated the functional
      mechanism of pBD2 antibacterial activity. Escherichia coli was incubated with
      different pBD2 concentrations for different times. Electron microscopy was used
      to analyze the locations of pBD2 and its induced morphological changes in E.
      coli. Gene expression analysis was also performed to further understand the
      molecular changes of E. coli in response to pBD2 incubation. The results
      demonstrated that E. coli membranes were broken, holed, and wrinkled after
      treatment with pBD2, and pBD2 was located on the cell membranes and manly in the
      cytoplasm. Furthermore, 38 differentially expressed genes (DEGs) were detected,
      successfully sequenced and confirmed by quantitative real-time PCR (qRT-PCR).
      Most of the known functional DEGs were associated with DNA transcription and
      translation and located in the cytoplasm. Collectively, the results suggest that
      pBD2 could have multiple modes of action and the main mechanism for killing E.
      coli might be influence on DNA transcription and translation by targeting
      intracellular molecules after membrane damage, although transport and metabolism
      proteins were also affected.

PMID- 30279558
TI  - Dynamics of error-related activity in deterministic learning - an EEG and fMRI
      study.
AB  - There is a close relationship between progress in learning and the error
      monitoring system. EEG and fMRI studies using probabilistic learning have
      revealed the distinct dynamics of this system after response and feedback, i.e.
      an increase of error-related and a decrease of feedback-related activity in the
      anterior cingulate cortex (ACC). Based on the existing theories, it can be
      presumed that during deterministic learning feedback-related activity in ACC
      would also increase. Since these assumptions have not yet been confirmed, it can
      be only speculated based on the data from the probabilistic paradigms how the
      information is being integrated within the ACC during deterministic learning.
      Here we implemented the Paired Associate Deterministic Learning task to the EEG
      and fMRI experiments. The analysis of EEG data showed a significant increase in
      the amplitude for both ERN and FN. Similarly, the fMRI results showed an increase
      in response-related and feedback-related activity of the ACC in erroneous trials.
      Our findings are in line with the current theories of ACC function: increasing
      ACC activity can be linked to the detected discrepancy between expected and
      obtained outcomes. We argue that expectancy violations in the course of
      deterministic learning are signalled by both, internal and external evaluation
      system.

PMID- 30279559
TI  - Profiling circRNA and miRNA of radiation-induced esophageal injury in a rat
      model.
AB  - Evidence has also shown that micro ribonucleic acid (miRNA) plays an important
      role in many cellular processes. However, it is unclear how ionizing radiation
      causes the miRNA and circular ribonucleic acid (circRNA) expression levels to
      change and how this change relates to esophageal injury. We analyzed RNA
      Sequencing (RNA-seq) data from normal esophageal tissue and irradiated esophageal
      tissues and used computational approaches to identify and characterize
      differentially expressed miRNAs and circRNAs. We detected 27 miRNAs and 197
      circRNAs that had significantly different expression levels after ionizing
      radiation treatment compared with normal control.Among the 27 miRNAs, 7 miRNAs
      were down-regulated, and the other 20 were up-regulated. Their target genes were
      found to be involved in responses to wound, lipid biosynthesis, cell
      proliferation, cell migration, chemokine activity, hairpin binding, and the cell
      membrane system. We also found 197 differentially expressed circRNAs in total, of
      which 87 were up-regulated and 110 were down-regulated. Notably, we found that
      differentially expressed circRNAs were enriched in cell differentiation,
      epithelial cell migration, striatum development, protein binding, extracellular
      exosome, and focal adhesion functions. Of the related processes, sphingolipid
      metabolism was notable. Many of the differentially expressed circRNAs were
      involved in sphingolipid metabolism pathways. Cells responded to ionizing
      radiation (IR) using multiple pathways, which led to sphingolipid metabolism and
      other immune responses, ultimately leading to esophageal injury.IR-induced
      esophageal injury is worth studying, especially the dynamic network of circRNA
      and miRNA. By knowing the regulatory details of related pathways, radiation
      related esophageal injury can be prevented, and the efficiency of radiation
      therapy can be enhanced.

PMID- 30279560
TI  - Correction: Prefrontal GABA levels, hippocampal resting perfusion and the risk of
      psychosis.
AB  - This article was originally published under NPG's License to Publish, but has now
      been made available under a [CC BY 4.0] license. The PDF and HTML versions of the
      paper have been modified accordingly.

PMID- 30279562
TI  - Resilience to climate variation in a spatially structured amphibian population.
AB  - Understanding the impact of weather fluctuations on demographic parameters is of
      crucial interest to biodiversity research in a context of global climate change.
      Amphibians are valuable candidates for investigating this topic due to their
      strong physiological dependence on water availability and temperature. In this
      study, we took advantage of data from a long-term capture-mark-recapture (CMR)
      monitoring program of a great crested newt (Triturus cristatus) population
      inhabiting a 12-pond archipelago in southeastern France. We investigated the
      interactions between vital rates (survival and recruitment), the internal
      structure of the population, and climatic variables both at a local and a
      regional (North Atlantic Oscillation: NAO) scale. Overall, we found a weak
      relationship between climatic variables and the survival of large-bodied newts.
      The only strong relationship was found to be a high NAO index during the post
      breeding period, suggesting that dry, hot summers negatively impact survival. In
      terms of recruitment, the results indicated that hot weather during the activity
      period had delayed deleterious effects on adult recruitment two years later,
      suggesting high larval and juvenile mortality due to unsuitable growing
      conditions. Recruitment was also impacted by a high NAO index during the
      overwintering period preceding recruitment, suggesting that mild weather
      increases the mortality of juveniles, probably by enhancing the depletion of
      energy reserves without any possibility of refueling.

PMID- 30279561
TI  - In Utero Heat Stress Alters the Offspring Epigenome.
AB  - Exposure to intrauterine heat stress during late gestation affects offspring
      performance into adulthood. However, underlying mechanistic links between thermal
      insult in fetal life and postnatal outcomes are not completely understood. We
      examined morphology, DNA methylation, and gene expression of liver and mammary
      gland for bull calves and heifers that were gestated under maternal conditions of
      heat stress or cooling (i.e. in utero heat stressed vs. in utero cooled calves).
      Mammary tissue was harvested from dairy heifers during their first lactation and
      liver from bull calves at birth. The liver of in utero heat stressed bull calves
      contained more cells and the mammary glands of in utero heat stressed heifers
      were comprised of smaller alveoli. We identified more than 1,500 CpG sites
      differently methylated between maternal treatment groups. These CpGs were
      associated with approximately 400 genes, which play a role in processes, such as
      development, innate immune defense, cell signaling, and transcription and
      translation. We also identified over 100 differentially expressed genes in the
      mammary gland with similar functions. Interestingly, fifty differentially
      methylated genes were shared by both bull calf liver and heifer mammary gland.
      Intrauterine heat stress alters the methylation profile of liver and mammary DNA
      and programs their morphology in postnatal life, which may contribute to the
      poorer performance of in utero heat stressed calves.

PMID- 30279564
TI  - Exacerbated fires in Mediterranean Europe due to anthropogenic warming projected
      with non-stationary climate-fire models.
AB  - The observed trend towards warmer and drier conditions in southern Europe is
      projected to continue in the next decades, possibly leading to increased risk of
      large fires. However, an assessment of climate change impacts on fires at and
      above the 1.5  degrees C Paris target is still missing. Here, we estimate future
      summer burned area in Mediterranean Europe under 1.5, 2, and 3  degrees C global
      warming scenarios, accounting for possible modifications of climate-fire
      relationships under changed climatic conditions owing to productivity
      alterations. We found that such modifications could be beneficial, roughly
      halving the fire-intensifying signals. In any case, the burned area is robustly
      projected to increase. The higher the warming level is, the larger is the
      increase of burned area, ranging from ~40% to ~100% across the scenarios. Our
      results indicate that significant benefits would be obtained if warming were
      limited to well below 2  degrees C.

PMID- 30279566
TI  - 'FORWARD GENETICS' AND THE CAUSES OF ALS.

PMID- 30279563
TI  - The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell
      metabolic state, and self-renewal.
AB  - Pw1/Peg3 is an imprinted gene expressed from the paternally inherited allele.
      Several imprinted genes, including Pw1/Peg3, have been shown to regulate overall
      body size and play a role in adult stem cells. Pw1/Peg3 is expressed in muscle
      stem cells (satellite cells) as well as a progenitor subset of muscle
      interstitial cells (PICs) in adult skeletal muscle. We therefore examined the
      impact of loss-of-function of Pw1/Peg3 during skeletal muscle growth and in
      muscle stem cell behavior. We found that constitutive loss of Pw1/Peg3 function
      leads to a reduced muscle mass and myofiber number. In newborn mice, the
      reduction in fiber number is increased in homozygous mutants as compared to the
      deletion of only the paternal Pw1/Peg3 allele, indicating that the maternal
      allele is developmentally functional. Constitutive and a satellite cell-specific
      deletion of Pw1/Peg3, revealed impaired muscle regeneration and a reduced
      capacity of satellite cells for self-renewal. RNA sequencing analyses revealed a
      deregulation of genes that control mitochondrial function. Consistent with these
      observations, Pw1/Peg3 mutant satellite cells displayed increased mitochondrial
      activity coupled with accelerated proliferation and differentiation. Our data
      show that Pw1/Peg3 regulates muscle fiber number determination during fetal
      development in a gene-dosage manner and regulates satellite cell metabolism in
      the adult.

PMID- 30279565
TI  - Facial expression and oxytocin as possible markers of positive emotions in
      horses.
AB  - Behavioural and physiological markers of discrete positive emotions remain little
      investigated in animals. To characterise new markers in horses, we used tactile
      stimulations to induce emotional situation of contrasting valence. In the Gentle
      grooming group (G, N = 13) horses were gently groomed during 11 sessions on the
      body areas they appreciated the most. Horses in the Standard grooming group (S, N
      = 14) were groomed using a fixed procedure, reported to induce avoidance
      reactions in some horses. At session 11, G horses expressed significantly more
      contact-seeking behaviours than S horses, which expressed significantly more
      avoidance behaviours. This result suggests positive emotions in G horses and
      negative emotions in S horses. Blood cortisol, oxytocin, heart rate and heart
      rate variability never differed between before and after the grooming session.
      However, after the 11 sessions, basal oxytocin levels were lower in the G than in
      the S group. This difference was unexpected, but supports studies showing that a
      low level of basal oxytocin could be a marker of better well-being. Analyses of
      facial expressions during grooming revealed significant differences between
      groups. These expressions appear to be more sensitive than behavioural indicators
      because they alone enabled differentiating emotions according to the group when
      horses were re-exposed to neutral grooming one year after the treatment.

PMID- 30279568
TI  - Relationship between the Second to Fourth Finger Length Ratio and Calcaneus
      Quantitative Ultrasound.
AB  - This study aimed to characterize the relationship between the ratio of the length
      of the second and fourth fingers (2D:4D value) and the speed of sound of the
      calcaneus by quantitative ultrasound (QUS-SOS) in undergraduate female students.
      We recruited 138 young women with a mean age of 19.6 +/- 1.4 years. The
      participants' calcaneus QUS-SOS was measured using an ultrasound bone
      densitometer. We also measured the participants' weight, height, and grip
      strength. A self-reported questionnaire was used to obtain information on
      participants' secondary sexual characteristics, and exercise habits. The present
      study showed that the 2D:4D value of both hands was significantly correlated with
      the calcaneus QUS-SOS. The 2D:4D value of the left hand was also positively
      associated with the calcaneus QUS-SOS results in several respects. These findings
      suggest that the 2D:4D value may be useful for the screening of risk for a low
      bone quality in undergraduate female students.

PMID- 30279567
TI  - Autophagy and Akt in the protective effect of erythropoietin helix B surface
      peptide against hepatic ischaemia/reperfusion injury in mice.
AB  - Helix B surface peptide (HBSP) is an erythropoietin (EPO)-derived peptide that
      protects tissue from the risks of elevated blood pressure and thrombosis. This
      study focused on the protection of HBSP in hepatic ischaemia/reperfusion (I/R) by
      enhancing the level of autophagy. In detail, we randomly divided C57BL/6 mice
      into sham-operated, hepatic ischaemia/reperfusion (I/R), I/R + HBSP, I/R + HBSP +
      3-methyladenine (autophagy inhibitor), I/R + HBSP + rapamycin (mTOR inhibitor),
      and I/R + HBSP + Ly294002 (Akt inhibitor) groups. We assessed alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and lactate
      dehydrogenase (LDH) levels in mouse sera, and performed haematoxylin/eosin (HE)
      staining, immunohistochemistry, electron microscopy, immunofluorescence
      microscopy, and western blotting on liver tissue to detect the degree of liver
      injury, liver apoptosis, autophagy, and the expression of microtubule associated
      protein 1 light chain 3 alpha (Map1lc3, or LC3), Beclin 1, phospho-mTOR, mTOR,
      phospho-Akt (P-Akt), and Akt. HBSP relieved hepatic I/R injury in a concentration
      independent manner. The expression of LC3II, LC3I, and Beclin 1, and the
      formation of autophagosomes, in the I/R + HBSP group were higher than those in
      the I/R group. The protective effects of HBSP were abolished by 3-methyladenine
      and, to a lesser extent, Ly294002, but enhanced by rapamycin. Furthermore, In
      vivo, HBSP also protected against hypoxia injury induced by cobalt chloride
      (CoCl2) through improving the level of autophagy. Therefore, HBSP protected
      against hepatic I/R injury, mainly via regulating autophagy by targeting mTOR.

PMID- 30279569
TI  - Publisher Correction: Critical Southern Ocean climate model biases traced to
      atmospheric model cloud errors.
AB  - 'In the original HTML version of this Article, ref.12 was incorrectly cited in
      the first sentence of the first paragraph of the Introduction. The correct
      citation is ref. 2. This has now been corrected in the HTML version of the
      Article; the PDF version was correct at the time of publication.'

PMID- 30279571
TI  - Surfactant/organic solvent free single-step engineering of hybrid graphene
      Pt/TiO2 nanostructure: Efficient photocatalytic system for the treatment of
      wastewater coming from textile industries.
AB  - In this study, hybrid graphene-Pt/TiO2 nanostructure were synthesized by single
      step, inexpensive and surfactant/organic solvent free route; hydrothermal
      technique. The physicochemical properties of hybrid graphene-Pt/TiO2
      nanostructure were carefully analyzed by multiple techniques, including X-ray
      diffractometer (XRD), X-ray photoelectron spectroscopy (XPS), field emission
      scanning electron microscope (FESEM) and transmission electron microscope (TEM).
      The synthesized hybrid nanostructures were utilized as photocatalyst for the
      degradation of methylene blue (MB) dye under natural environment at average
      ambient temperature and mean daily global solar radiation, of about 22-25 
      degrees C and 374.9 mWh/cm2, respectively. The activity performance indicated
      considerable degradation of methylene blue (MB) dye and was in the following
      order Gr (13%), TiO2 (60%) and hybrid graphene-Pt/TiO2 nanostructure (90%) over
      21 min under the natural light illumination. The physiochemical characterization
      suggests that, the tightly attached metalized TiO2 nanoparticles (Pt-TiO2) on the
      high surface area graphene sheets improved utilization of visible light and
      increased separation and transfer of photo-excited electron (e) hole (h+) pairs.
      Notably, the hybrid graphene-Pt/TiO2 nanostructure exhibited an excellent cyclic
      stability for methylene blue (MB) dye removal. Finally, the kinetic behavior
      indicated that the photocatalytic degradation reaction of the dye obeyed the
      pseudo-first order (Langmuir-Hinshelwood) kinetics model.

PMID- 30279570
TI  - Reconstructing the evolutionary history of pandemic foot-and-mouth disease
      viruses: the impact of recombination within the emerging O/ME-SA/Ind-2001
      lineage.
AB  - Foot-and-mouth disease (FMD) is a highly contagious disease of livestock
      affecting animal production and trade throughout Asia and Africa. Understanding
      FMD virus (FMDV) global movements and evolution can help to reconstruct the
      disease spread between endemic regions and predict the risks of incursion into
      FMD-free countries. Global expansion of a single FMDV lineage is rare but can
      result in severe economic consequences. Using extensive sequence data we have
      reconstructed the global space-time transmission history of the O/ME-SA/Ind-2001
      lineage (which normally circulates in the Indian sub-continent) providing
      evidence of at least 15 independent escapes during 2013-2017 that have led to
      outbreaks in North Africa, the Middle East, Southeast Asia, the Far East and the
      FMD-free islands of Mauritius. We demonstrated that sequence heterogeneity of
      this emerging FMDV lineage is accommodated within two co-evolving divergent
      sublineages and that recombination by exchange of capsid-coding sequences can
      impact upon the reconstructed evolutionary histories. Thus, we recommend that
      only sequences encoding the outer capsid proteins should be used for broad-scale
      phylogeographical reconstruction. These data emphasise the importance of the
      Indian subcontinent as a source of FMDV that can spread across large distances
      and illustrates the impact of FMDV genome recombination on FMDV molecular
      epidemiology.

PMID- 30279573
TI  - Pre-transplant expressions of microRNAs, comorbidities, and post-transplant
      mortality.
AB  - We analyzed micro-RNAs (miRs) as possible diagnostic biomarkers for relevant
      comorbidities prior to and prognostic biomarkers for mortality following
      hematopoietic cell transplantation (HCT). A randomly selected group of patients
      (n = 36) were divided into low-risk (HCT-comorbidity index [HCT-CI] score of 0
      and survived HCT) and high-risk (HCT-CI scores >= 4 and deceased after HCT)
      groups. There were 654 miRs tested and 19 met the pre-specified significance
      level of p < 0.1. In subsequent models, only eight miRs maintained statistical
      significance in regression models after adjusting for baseline demographic
      factors; miRs-374b and -454 were underexpressed, whereas miRs-142-3p, -191, -424,
      -590-3p, -29c, and -15b were overexpressed among high-risk patients relative to
      low-risk patients. Areas under the curve for these eight miRs ranged between 0.74
      and 0.81, suggesting strong predictive capacity. Consideration of miRs may
      improve risk assessment of mortality and should be further explored in larger
      future prospective studies.

PMID- 30279572
TI  - Urinary Exosomal and cell-free DNA Detects Somatic Mutation and Copy Number
      Alteration in Urothelial Carcinoma of Bladder.
AB  - Urothelial bladder carcinoma (UBC) is characterized by a large number of genetic
      alterations. DNA from urine is a promising source for liquid biopsy in urological
      malignancies. We aimed to assess the availability of cell-free DNA (cfDNA) and
      exosomal DNA (exoDNA) in urine as a source for liquid biopsy in UBC. We included
      9 patients who underwent surgery for UBC and performed genomic profiling of tumor
      samples and matched urinary cfDNA and exoDNA. For mutation analysis, deep
      sequencing was performed for 9 gene targets and shallow whole genome sequencing
      (sWGS) was used for the detection of copy number variation (CNV). We analyzed
      whether genetic alteration in tumor samples was reflected in urinary cfDNA or
      exoDNA. To measure the similarity between copy number profiles of tumor tissue
      and urinary DNA, the Pearson's correlation coefficient was calculated. We found
      17 somatic mutations in 6 patients. Of the 17 somatic mutations, 14 and 12 were
      identified by analysis of cfDNA and exoDNA with AFs of 56.2% and 65.6%,
      respectively. In CNV analysis using sWGS, although the mean depth was 0.6X, we
      found amplification of MDM2, ERBB2, CCND1 and CCNE1, and deletion of CDKN2A, PTEN
      and RB1, all known to be frequently altered in UBC. CNV plots of cfDNA and exoDNA
      showed a similar pattern with those from the tumor samples. Pearson's correlation
      coefficients of tumor vs. cfDNA (0.481) and tumor vs. exoDNA (0.412) were higher
      than that of tumor vs. normal (0.086). We successfully identified somatic
      mutations and CNV in UBC using urinary cfDNA and exoDNA. Urinary exoDNA could be
      another source for liquid biopsy. Also, CNV analysis using sWGS is an alternative
      strategy for liquid biopsy, providing data from the whole genome at a low cost.

PMID- 30279574
TI  - Prof. Franco Mandelli: Leukaemia therapy pioneer.

PMID- 30279575
TI  - The effect of NIMA matching in adult unrelated mismatched hematopoietic stem cell
      transplantation - a joint study of the Acute Leukemia Working Party of the EBMT
      and the CIBMTR.
AB  - Hematological malignancies can be cured by unrelated donor allogeneic HSCT and
      outcomes are optimized by high-resolution HLA matching at HLA-A, -B, -C, -DRB1
      and -DQB1 (10/10 match). If a 10/10 match is unavailable, 9/10 matches may be
      suitable. Fetal exposure to non-inherited maternal antigens (NIMA) may impart
      lifelong NIMA tolerance modulating the immune response, as shown in adult
      haploidentical transplantation. In cord blood transplantation, NIMA matching
      lowered rates of aGvHD and TRM; in haploidentical transplantation, sibling donors
      with non-shared maternal antigens showed less grade II-IV aGvHD. This
      retrospective analysis examined if 9/10 matched unrelated donor HSCT benefits
      from NIMA matching. DKMS contacted 1,735 donors and obtained 733 (42%) maternal
      samples. NIMA-matched and -mismatched cases with a minimum follow-up of 1 year
      were compared by univariate and multivariate analyses adjusted for co-variates
      for OS, DFS, relapse, TRM and a/cGvHD. The study population (N = 445) comprised
      31 NIMA-matched and 414 NIMA-mismatched cases. No significant differences between
      NIMA-matched and NIMA-mismatched groups were found for any outcomes with similar
      OS and TRM rates within both groups. This study provides the proof of principle
      that NIMA matching is possible in the unrelated donor HSCT setting; larger
      studies may be able to provide significant results.

PMID- 30279577
TI  - Updates in advanced prostate cancer 2018.

PMID- 30279576
TI  - Publisher Correction: The NORAD lncRNA assembles a topoisomerase complex critical
      for genome stability.
AB  - A typo in the 'Reviewer information' section of this Letter was corrected online.

PMID- 30279578
TI  - Prostate cancer disparities in Hispanics by country of origin: a nationwide
      population-based analysis.
AB  - BACKGROUND: We sought to evaluate prostate cancer (PCa) characteristics and
      outcomes of Hispanics living in the United States by country of origin in the
      Surveillance, Epidemiology and End Results (SEER) program. METHODS: Retrospective
      analysis of 72,134 adult Hispanics with PCa between 1995 and 2014. Origin was
      Mexican (N = 16,995; 24%), South/Central American (N = 6949; 10%), Puerto Rican
      (N = 3582; 5%), Cuban (N = 2587; 4%), Dominican (N = 725; 1%), Hispanic not
      specified (NOS, N = 41,296; 57%), as coded by SEER. Patient and PCa
      characteristics were analyzed with chi-square and Kruskal-Wallis tests. Overall
      and PCa survival were analyzed with Kaplan-Meier and Cox models adjusting for
      baseline variables. RESULTS: At diagnosis, Mexicans had more advanced stage,
      higher prostate-specific antigen, and higher Gleason score while Cubans and
      Dominicans had more favorable PCa at diagnosis (all P < 0.05). After a median
      follow-up of 69 months, 20,317 men died, including 6223 PCa deaths. Compared to
      Mexicans, Cubans (HR = 1.22, 95% CI = [1.14-1.30]) and Puerto Ricans (HR = 1.15
      [1.08-1.22]) had worse overall survival while Dominicans (HR = 0.76 [0.64-0.91]),
      South/Central Americans (HR = 0.68 [0.65-0.72]), and NOS (HR = 0.81 [0.78-0.84])
      had better overall survival. Compared to Mexicans, Cubans (HR = 1.08 [0.96-1.22])
      and Puerto Ricans (HR = 1.03 [0.92-1.15]) had similar PCa survival while
      Dominicans (HR = 0.72 [0.53-0.98]), South/Central Americans (HR = 0.67 [0.60
      0.74]), and NOS (HR = 0.68 [0.64-0.73]) had significantly better PCa survival.
      CONCLUSIONS: Among Hispanics in the United States, disparities in PCa
      characteristics and survival by country of origin exist, with Dominicans,
      South/Central Americans, and Hispanic NOS having better PCa survival compared to
      Mexicans, Cubans, and Puerto Ricans.

PMID- 30279579
TI  - PTEN status assessment in the Johns Hopkins active surveillance cohort.
AB  - BACKGROUND: Up to half of men with Gleason score 6 (GS6) prostate cancers
      initially managed with active surveillance (AS) will eventually require
      definitive therapy, usually due to tumor grade reclassification during follow-up.
      We examined the association between PTEN status on biopsy and subsequent
      clinicopathologic outcomes in men with GS6 cancers who enrolled in AS. METHODS:
      We performed a case-control study of men enrolled in the Johns Hopkins AS cohort
      with diagnostic biopsy tissue available for immunohistochemical (IHC) staining.
      IHC was performed for PTEN using genetically validated protocols for all
      patients. Cases included men who underwent grade reclassification to GS >= 3 + 4
      = 7 on biopsy within 2 years of follow-up (i.e., early reclassification) or
      reclassification to GS >= 4 + 3 = 7 on biopsy or radical prostatectomy during
      follow-up (i.e., extreme reclassification). Control patients were diagnosed with
      GS6 cancer and monitored on AS for at least 8 years without undergoing biopsy
      reclassification. RESULTS: Among 67 cases with adequate tissue, 31 men underwent
      early reclassification and 36 men underwent extreme reclassification. Cases were
      compared to 65 control patients with adequate tissue for assessment. On initial
      prostate biopsy, cases were older (median age 67 vs. 65, p = 0.024) and were less
      likely to meet very-low-risk criteria (64 vs 79%, p = 0.042) as compared to
      controls. Although not statistically significant, PTEN loss was observed in only
      1 (1.5%) of 65 controls as compared to 6 (9%) of 67 cases (p = 0.062).
      CONCLUSIONS: PTEN loss was rare among men with GS6 prostate cancer enrolled in AS
      at Johns Hopkins. Despite this, PTEN loss was more frequent among men who
      underwent early or extreme reclassification to higher-grade cancer as compared to
      controls. Additional studies in larger low-risk cohorts may better elucidate a
      potential role for PTEN in selecting patients for AS.

PMID- 30279580
TI  - Impact of age on exposure to oral antiandrogen therapies in clinical practice.
AB  - BACKGROUND: Oral antiandrogen therapies are predominantly used in older men, but
      real-life studies evaluating the impact of age on pharmacokinetic exposure are
      lacking. This study aims to evaluate the impact of age on the pharmacokinetic
      profiles of abiraterone acetate and enzalutamide in clinical practice. PATIENTS
      AND METHODS: Retrospective observational study to evaluate the impact of age on
      the first steady-state sample of patients treated with abiraterone acetate or
      enzalutamide in routine daily clinical practice. The effect of age on target
      attainment was assessed. RESULTS: For abiraterone acetate and enzalutamide, 71
      and 64 patients were included, respectively. Baseline patients' characteristics
      and administered doses were not age-dependent. No age-related differences were
      observed in exposure to the main metabolites of abiraterone acetate, except for
      active metabolite Delta(4)-Abiraterone (D4A) with a median plasma concentration
      of 2.5 * 10-3 mg/L in the oldest versus 1.3 * 10-3 mg/L in the youngest age
      quartile (coefficient of variation, CV, 72%, p = 0.03). For enzalutamide, no
      significant differences in exposure were found, except for carboxylic acid
      enzalutamide, having a median plasma concentration of 5.8 mg/L versus 3.9 mg/L in
      the oldest versus the youngest age quartile (CV 66%, p = 0.03). However, this was
      driven by one patient aged 99 years old. Age had no significant influence on
      target attainment of either compound. CONCLUSIONS: This study showed no
      significant impact of age on the pharmacokinetic profiles of abiraterone acetate
      and enzalutamide, except for the active metabolite D4A and the inactive
      metabolite carboxylic acid enzalutamide, both having significantly higher
      exposure in older males. Target attainments of abiraterone and enzalutamide were
      not significantly affected by age, which suggests that age has no clinically
      relevant impact on exposure to these oral antiandrogen therapies. However, the
      clinical impact of higher exposure to D4A in older males remains undetermined.

PMID- 30279581
TI  - Predictors of fluoroquinolone-resistant bacteria in the rectal vault of men
      undergoing prostate biopsy.
AB  - IMPORTANCE: Fluoroquinolone (FQ)-resistant rectal vault flora is associated with
      infectious complications in men undergoing transrectal ultrasound-guided prostate
      needle biopsy (TRUS-PNB). OBJECTIVE: To determine the patient factors that
      predict FQ-resistant rectal cultures in men who are undergoing transrectal
      ultrasound-guided prostate needle biopsy. METHODS: An IRB approved retrospective
      review of 6183 consecutive men who had undergone a rectal swab culture in
      preparation for TRUS-PNB between January 2013 and December 2014 was performed.
      Multivariable logistic regression was used to determine the clinical and
      demographic factors associated with FQ-resistant Enterobacteriaceae in the rectal
      vault. RESULTS: Of the 6179 rectal swabs analyzed, 4842 (78%) were FQ-sensitive,
      and 1337 (22%) were FQ-resistant. On univariable analysis, increasing age, prior
      TRUS-PNB, higher number of biopsy cores obtained, diabetes mellitus,
      antimicrobial use within the past 6 months and non-Caucasian race were predictors
      of FQ-resistance (all p < 0.05). Men with FQ-resistant cultures were more likely
      to have benign pathology on TRUS-PNB (p = 0.004). On multivariable analysis,
      increasing patient age (OR = 1.01/year [1.00-1.02]), use of antimicrobials in the
      last 6 months (OR = 2.85[2.18-3.72]), African American (OR = 1.99 [1.66-2.37]),
      Asian (OR = 3.39 [2.63-4.37]), and Hispanic (OR = 2.10 [1.72-2.55]) races were
      independently associated with FQ-resistant rectal cultures. The overall
      infectious rate was 1.1% (56/5214) and the sepsis rate was 0.46% (24/5214). The
      infection rate in the FQ-resistant group was 3.9% (43/1107) compared to FQ
      sensitive group 0.3% (13/4107), p < 0.001. CONCLUSION: In this cohort, increasing
      age, recent antimicrobial-use, and non-Caucasian race were independent predictors
      of FQ-resistance in the rectal vault. As FQ-resistance is associated with
      infectious complications from transrectal ultrasound-guided prostate needle
      biopsy, understanding risk factors may assist infection control efforts.

PMID- 30279582
TI  - Impact of age, comorbidity, and PSA doubling time on long-term competing risks
      for mortality among men with non-metastatic castration-resistant prostate cancer.
AB  - BACKGROUND: Understanding competing risks for mortality is critical in
      determining prognosis among men with non-metastatic castration-resistant prostate
      cancer (nmCRPC), a disease state that often affects older men and has substantial
      heterogeneity in risk of cancer mortality. We sought to determine the impact of
      age, comorbidity, and PSA doubling time (PSADT) on competing risks for mortality
      in men with nmCRPC. METHODS: We conducted a retrospective analysis of 1238
      patients diagnosed with nmCRPC in 2000-2015 in the SEARCH database. Multivariable
      Cox proportional hazards and competing risks regression were used to determine
      the hazards of overall, prostate cancer-specific (PCSM), and other-cause
      mortality (OCM) across age, Charlson comorbidity index (CCI), and PSADT
      subgroups. RESULTS: Men with nmCRPC were elderly (median age 77) and had
      substantial comorbidity burdens (CCI > 1 n = 701, 57%). Multivariable Cox
      analysis showed higher CCI was associated with higher hazard of OCM, while slower
      PSADT was associated with lower hazard of PCSM across all age subgroups. Among
      those with CCI >= 3 (vs. CCI0), the hazard ratio of OCM was 2.7 (95% CI 1.1-6.3),
      2.0 (95% CI 1.1-3.6), and 2.5 (95% CI 1.5-4.0) for those aged <70, 70-79, and
      >=80, respectively. Among those with PSADT >= 9 months (vs. < 9 months), the
      hazard ratios for PCSM were 0.5 (95% CI 0.3-0.9), 0.6 (95% CI 0.4-0.9), and 0.6
      (95% CI 0.4-0.9) for those aged <70, 70-79, and >=80. Competing risks curves
      revealed PCSM was the predominant cause of death for those with PSADT < 9 months
      across all age and comorbidity groups. PCSM and OCM were relatively equal
      competitors for mortality among those with PSADT>=9 months except those aged > 80
      with CCI >= 3, in whom OCM was the predominant cause of death. CONCLUSIONS: Among
      men with nmCRPC, age, comorbidity, and PSADT are associated with risk and cause
      of death and may assist clinicians in counseling patients regarding cancer
      prognosis.

PMID- 30279584
TI  - Nutrition care guidelines for men with prostate cancer undergoing androgen
      deprivation therapy: do we have enough evidence?
AB  - BACKGROUND: To review the evidence available to support clinical practice
      guidelines for dietary interventions aimed at mitigating the side effects of
      androgen deprivation therapy (ADT) in men with prostate cancer, and to identify
      future research priorities. METHODS: An analytical model was designed to select
      and interpret evidence for the effect of dietary interventions on ADT side
      effects. Key terms identified articles that investigated dietary interventions to
      mitigate ADT side effects among men treated for prostate cancer. Medline, Embase,
      Proquest, CINAHL, Cochrane databases, and PubMed were searched from inception
      through June, 2018. Clinical trial registries were also searched for up-to-date
      study protocols. Articles were not restricted on design. Methodological quality
      was assessed using the mixed methods appraisal tool. RESULTS: Sixteen articles
      met inclusion criteria, each with distinct dietary interventions. Twelve studies
      used interventions that combined diet with physical activity and/or medication
      and/or counselling. Four articles examined the effect of diet alone on ADT side
      effects. Of those, three articles measured changes to participants' dietary
      intake and influence on ADT side effects. One article showed daily caffeinated
      beverages improved cancer-related fatigue. Two articles showed no impact of
      isoflavone supplementation on hot flushes, quality of life, body mass index, or
      blood lipids. Dietary intake and compliance was poorly reported across all
      studies limiting knowledge of acceptability and feasibility for dietary
      interventions. Information on the nutrition care practices and views of
      clinicians treating men for prostate cancer is limited. No articles measured the
      impact of diet on long-term ADT side effects. Methodological quality of included
      papers ranged from weak to strong. CONCLUSIONS: Current evidence for dietary
      interventions to mitigate ADT side effects is limited. Further investigations are
      warranted to explore the impact of changes in dietary intake on ADT side effects
      before practice guidelines can be considered.

PMID- 30279583
TI  - Prostate Imaging Compared to Transperineal Ultrasound-guided biopsy for
      significant prostate cancer Risk Evaluation (PICTURE): a prospective cohort
      validating study assessing Prostate HistoScanning.
AB  - BACKGROUND: Men with negative prostate biopsies or those diagnosed with low-risk
      or low-volume intermediate-risk prostate cancers often require a second prostate
      biopsy prior to a treatment decision. Prostate HistoScanning (PHS) is an
      ultrasound imaging test that might inform prostate biopsy in such men. METHODS:
      PICTURE was a prospective, paired-cohort validating trial to assess the
      diagnostic accuracy of imaging in men requiring a further biopsy
      (clinicaltrials.gov, NCT01492270) (11 January 2012-29 January 2014). We enrolled
      330 men who had undergone a prior TRUS biopsy but where diagnostic uncertainty
      remained. All eligible men underwent PHS and transperineal template prostate
      mapping (TTPM) biopsy (reference standard). Men were blinded to the imaging
      results until after undergoing TTPM biopsies. We primarily assessed the ability
      of PHS to rule out clinically significant prostate (negative predictive value
      [NPV] and sensitivity) for a target histological condition of Gleason >=4+3
      and/or a cancer core length (MCCL) >=6 mm. We also assessed the role of visually
      estimated PHS-targeted biopsies. RESULTS: Of the 330 men enrolled, 249 underwent
      both PHS and TTPM biopsy. Mean (SD) age was 62 (7) years, median (IQR) PSA 6.8
      (4.98-9.50) ng/ml, median (IQR) number of previous biopsies 1 (1-2) and mean (SD)
      gland size 37 (15.5) ml. One hundred and forty six (59%) had no clinically
      significant cancer. PHS classified 174 (70%) as suspicious. Sensitivity was 70.3%
      (95% CI 59.8-79.5) and NPV 41.3% (95% CI 27.0-56.8). Specificity and positive
      predictive value (PPV) were 14.7% (95% CI 9.1-22.0) and 36.8% (95% CI 29.6-44.4),
      respectively. In all, 213/220 had PHS suspicious areas targeted with targeting
      sensitivity 13.6% (95% CI 7.3-22.6), specificity 97.6% (95% CI 93.1-99.5), NPV
      61.6% (95% CI 54.5-68.4) and PPV 80.0% (95% CI 51.9-95.7). CONCLUSIONS: PHS is
      not a useful test in men seeking risk stratification following initial prostate
      biopsy.

PMID- 30279585
TI  - Computational analysis of the amino acid interactions that promote or decrease
      protein solubility.
AB  - The solubility of globular proteins is a basic biophysical property that is
      usually a prerequisite for their functioning. In this study, we probed the
      solubility of globular proteins with the help of the statistical potential
      formalism, in view of objectifying the connection of solubility with structural
      and energetic properties and of the solubility-dependence of specific amino acid
      interactions. We started by setting up two independent datasets containing either
      soluble or aggregation-prone proteins with known structures. From these two
      datasets, we computed solubility-dependent distance potentials that are by
      construction biased towards the solubility of the proteins from which they are
      derived. Their analysis showed the clear preference of amino acid interactions
      such as Lys-containing salt bridges and aliphatic interactions to promote protein
      solubility, whereas others such as aromatic, His-pi, cation-pi, amino-pi and
      anion-pi interactions rather tend to reduce it. These results indicate that
      interactions involving delocalized pi-electrons favor aggregation, unlike those
      involving no (or few) dispersion forces. Furthermore, using our potentials
      derived from either highly or weakly soluble proteins to compute protein folding
      free energies, we found that the difference between these two energies correlates
      better with solubility than other properties analyzed before such as protein
      length, isoelectric point and aliphatic index. This is, to the best of our
      knowledge, the first comprehensive in silico study of the impact of residue
      residue interactions on protein solubility properties.The results of this
      analysis provide new insights that will facilitate future rational protein design
      applications aimed at modulating the solubility of targeted proteins.

PMID- 30279587
TI  - Synthesis and Evaluation of Herbal Chitosan from Ganoderma Lucidum Spore Powder
      for Biomedical Applications.
AB  - Chitosan is an extremely valuable biopolymer and is usually obtained as a
      byproduct from the shells of crustaceans. In the current work, chitosan is
      obtained from an herbal source (Ganoderma lucidum spore powder (GLSP)) for the
      first time. To show this, both standard (thermochemical deacetylation, (TCD)) and
      emerging (ultrasound-assisted deacetylation (USAD)) methods of chitosan
      preparation were used. The obtained chitosan was characterized by elemental
      analysis, XRD (X-ray diffraction), FT-IR (Fourier transform infrared
      spectroscopy) and thermogravimetric measurements. The process resulted in
      chitosan possessing comparable values of DD, [eta] and [Formula: see text] to the
      commercial product. Chitosan obtained via both processes (TCD and USAD) displayed
      excellent biocompatibility; although the USAD prepared biopolymer exhibited
      significantly improved fibroblast (L929 cell) viability and enhanced
      antibacterial zones for both Escherichia coli (E. coli) and Staphylococcus aureus
      (S. aureus). The findings of new herbal chitosan mark key developments of natural
      biomaterials; marking a potential shift from conventional sea-based organisms.

PMID- 30279586
TI  - Supplementation with a selective amino acid formula ameliorates muscular
      dystrophy in mdx mice.
AB  - Duchenne muscular dystrophy (DMD) is one of the most common and severe forms of
      muscular dystrophy. Oxidative myofibre content, muscle vasculature architecture
      and exercise tolerance are impaired in DMD. Several studies have demonstrated
      that nutrient supplements ameliorate dystrophic features, thereby enhancing
      muscle performance. Here, we report that dietary supplementation with a specific
      branched-chain amino acid-enriched mixture (BCAAem) increased the abundance of
      oxidative muscle fibres associated with increased muscle endurance in dystrophic
      mdx mice. Amelioration of the fatigue index in BCAAem-treated mdx mice was caused
      by a cascade of events in the muscle tissue, which were promoted by endothelial
      nitric oxide synthase (eNOS) activation and vascular endothelial growth factor
      (VEGF) expression. VEGF induction led to recruitment of bone marrow (BM)-derived
      endothelial progenitors (EPs), which increased the capillary density of
      dystrophic skeletal muscle. Functionally, BCAAem mitigated the dystrophic
      phenotype of mdx mice without inducing dystrophin protein expression or replacing
      the dystrophin-associated glycoprotein (DAG) complex in the membrane, which is
      typically lost in DMD. BCAAem supplementation could be an effective adjuvant
      strategy in DMD treatment.

PMID- 30279589
TI  - Multivariate analysis of short time series in terms of ensembles of correlation
      matrices.
AB  - When dealing with non-stationary systems, for which many time series are
      available, it is common to divide time in epochs, i.e. smaller time intervals and
      deal with short time series in the hope to have some form of approximate
      stationarity on that time scale. We can then study time evolution by looking at
      properties as a function of the epochs. This leads to singular correlation
      matrices and thus poor statistics. In the present paper, we propose an ensemble
      technique to deal with a large set of short time series without any consideration
      of non-stationarity. Given a singular data matrix, we randomly select subsets of
      time series and thus create an ensemble of non-singular correlation matrices. As
      the selection possibilities are binomially large, we will obtain good statistics
      for eigenvalues of correlation matrices, which are typically not independent.
      Once we defined the ensemble, we analyze its behavior for constant and block
      diagonal correlations and compare numerics with analytic results for the
      corresponding correlated Wishart ensembles. We discuss differences resulting from
      spurious correlations due to repetitive use of time-series. The usefulness of
      this technique should extend beyond the stationary case if, on the time scale of
      the epochs, we have quasi-stationarity at least for most epochs.

PMID- 30279588
TI  - Allosteric Role of Substrate Occupancy Toward the Alignment of P-glycoprotein
      Nucleotide Binding Domains.
AB  - P-glycoprotein (Pgp) is an ATP-binding cassette transporter that eliminates
      toxins from the cell but causes multidrug resistance in chemotherapies. The
      crystal structures of Pgp revealed drug-like compounds bound to an inward-facing
      conformation in which the energy-harnessing nucleotide binding domains (NBDs)
      were widely separated with no interfacial interaction. Following drug binding,
      inward-facing Pgp must transition to an NBD dimer conformation to achieve ATP
      binding and hydrolysis at canonical sites defined by both halves of the
      interface. However, given the high degree of flexibility shown for this
      transporter, it is difficult to envision how NBDs overcome entropic
      considerations for achieving proper alignment in order to form the canonical ATP
      binding site. We explored the hypothesis that substrate occupancy of the
      polyspecific drug-binding cavity plays a role in the proper alignment of NBDs
      using computational approaches. We conducted twelve atomistic molecular dynamics
      (MD) simulations (100-300 ns) on inward-facing Pgp in a lipid bilayer with and
      without small molecule substrates to ascertain effects of drug occupancy on NBD
      dimerization. Both apo- and drug-occupied simulations showed NBDs approaching
      each other compared to the crystal structures. Apo-Pgp reached a pseudo
      dimerization in which NBD signature motifs for ATP binding exhibited a
      significant misalignment during closure. In contrast, occupancy of three
      established substrates positioned by molecular docking achieved NBD alignment
      that was much more compatible with a canonical NBD dimerization trajectory.
      Additionally, aromatic amino acids, known to confer the polyspecific drug-binding
      characteristic of the internal pocket, may also govern polyspecific drug access
      to the cavity. The enrichment of aromatics comprising the TM4-TM6 portal
      suggested a preferential pathway over the aromatic-poor TM10-TM12 for lateral
      drug entry from the lipid bilayer. Our study also suggested that drug
      polyspecificity is enhanced due to a synergism between multiple drug-domain
      interactions involving 36 residues identified in TM1, 5, 6, 7, 11 and 12.

PMID- 30279590
TI  - Heterogeneity of a landscape influences size of home range in a North American
      cervid.
AB  - In the northeastern United States, chronic wasting disease has recently been
      detected in white-tailed deer (Odocoileus virginianus) populations, and
      understanding the relationship between landscape configuration and home range may
      improve disease surveillance and containment efforts. The objectives of our study
      were to compare size of home range for deer occupying a continuum of forested
      landscapes and to investigate relationships between size of home range and
      measures of landscape configuration. We used a movement-based kernel density
      estimator to estimate home range at five spatial scales among deer across study
      areas. We developed 7 linear regression models that used measures of the
      configuration of the forested landscape to explain size of home range. We
      observed differences in size of home range between sexes among areas that
      differed based on landscape configuration. We documented size of home range
      changed with various metrics that identifying connectivity of forested patches.
      Generally, size of home range increased with an increasing proportion of
      homogenous forest. Our results suggest that deer in our region occupy a landscape
      at hierarchically-nested scales that is controlled by the connectivity of the
      forested landscape across local or broad geographical regions.

PMID- 30279593
TI  - Trump administration launches sweeping review of fetal-tissue research.

PMID- 30279591
TI  - An engineered arginine-rich alpha-helical antimicrobial peptide exhibits broad
      spectrum bactericidal activity against pathogenic bacteria and reduces bacterial
      infections in mice.
AB  - The increase in the prevalence of antibiotic-resistant bacteria has become a
      major public health concern. Antimicrobial peptides (AMPs) are emerging as
      promising candidates addressing this issue. In this study, we designed several
      AMPs by increasing alpha-helical contents and positive charges and optimizing
      hydrophobicity and amphipathicity in the Sushi 1 peptide from horseshoe crabs. A
      neural network-based bioinformatic prediction tool was used for the first stage
      evaluations of peptide properties. Among the peptides designed, Sushi-replacement
      peptide (SRP)-2, an arginine-rich and highly alpha-helical peptide, showed broad
      spectrum bactericidal activity against both Gram-positive and Gram-negative
      bacteria, including methicillin-resistant Staphylococcus aureus and multidrug
      resistant Acinetobacter baumannii; nevertheless, it showed little hemolytic and
      cytotoxic activity against mammalian cells. Atomic force microscopy results
      indicated that SRP-2 should interact directly with cell membrane components,
      resulting in bacterial cell death. SRP-2 also neutralized LPS-induced macrophage
      activation. Moreover, in an intraperitoneal multidrug-resistant A. baumannii
      infection mouse model, SRP-2 successfully reduced the bacterial number in ascitic
      fluid and tumor necrosis factor-alpha production. Our study findings demonstrate
      that bioinformatic calculations can be powerful tools to help design potent AMPs
      and that arginine is superior to lysine for providing positive charges for AMPs
      to exhibit better bactericidal activity and selectivity against bacterial cells.

PMID- 30279594
TI  - Why Canada's immigration regulations may be pushing postdocs out.

PMID- 30279595
TI  - South Africa's largest dinosaur upends theories of how four-legged walking began.

PMID- 30279596
TI  - What the Nobels are - and aren't - doing to encourage diversity.

PMID- 30279592
TI  - Effect of Differences in Metabolic Activity of Melanoma Models on Response to
      Lonidamine plus Doxorubicin.
AB  - Lonidamine (LND), a metabolic modulator, sensitizes DB-1 human melanoma to
      doxorubicin (DOX) chemotherapy by acidifying and de-energizing the tumor. This
      report compares the effects of LND on two human melanoma lines, DB-1 and WM983B,
      which exhibit different metabolic properties. Using liquid chromatography mass
      spectrometry and Seahorse analysis, we show that DB-1 was more glycolytic than
      WM983B in vitro. 31P magnetic resonance spectroscopy (MRS) indicates that LND
      (100 mg/kg, i.p.) induces similar selective acidification and de-energization of
      WM983B xenografts in immunosuppressed mice. Over three hours, intracellular pH
      (pHi) of WM983B decreased from 6.91 +/- 0.03 to 6.59 +/- 0.10 (p = 0.03), whereas
      extracellular pH (pHe) of this tumor changed from 7.03 +/- 0.05 to 6.89 +/- 0.06
      (p = 0.19). A decline in bioenergetics (beta-NTP/Pi) of 55 +/- 5.0% (p = 0.03)
      accompanied the decline in pHi of WM983B. Using 1H MRS with a selective
      multiquantum pulse sequence and Hadamard localization, we show that LND induced a
      significant increase in tumor lactate levels (p < 0.01). LND pre-treatment
      followed by DOX (10 mg/kg, i.v.) produced a growth delay of 13.7 days in WM983B
      (p < 0.01 versus control), a growth delay significantly smaller than the 25.4
      days that occurred with DB-1 (p = 0.03 versus WM983B). Differences in relative
      levels of glycolysis may produce differential therapeutic responses of DB-1 and
      WM983B melanomas.

PMID- 30279598
TI  - Degree completion linked to peer support.

PMID- 30279599
TI  - Supercharge your data wrangling with a graphics card.

PMID- 30279600
TI  - Cancer immunologists scoop medicine Nobel prize.

PMID- 30279601
TI  - From the archive.

PMID- 30279602
TI  - Physics Nobel won by laser wizardry - laureates include first woman in 55 years.

PMID- 30279603
TI  - Peru's oldest and largest Amazonian oil field poised for clean up.

PMID- 30279604
TI  - China t o train African scientists as part of $60-billion development plan.

PMID- 30279605
TI  - Super-tomato shows what plant scientists can do.

PMID- 30279608
TI  - Apomorphine infusion in advanced Parkinson disease.

PMID- 30279607
TI  - Sex-specific alterations in preterm brain.
AB  - BACKGROUND: The literature on brain imaging in premature infants is mostly made
      up of studies that evaluate neonates, yet the most dynamic time of brain
      development happens from birth to 1 year of age. This study was designed to
      obtain quantitative brain measures from magnetic resonance imaging scans of
      infants born prematurely at 12 months of age. METHODS: The subject group was
      designed to capture a wide range of gestational age (GA) from premature to full
      term infants. An age-specific atlas generated quantitative brain measures. A
      regression model was used to predict effects of GA and sex on brain measures.
      RESULTS: There was a primary effect of sex on: (1) intracranial volume, males >
      females; (2) proportional cerebral cortical gray matter (females > males), and
      (3) cerebral white matter (males > females). GA predicted cerebral volume and
      cerebral spinal fluid. GA also predicted cortical gray matter in a sex-specific
      manner with GA having a significant effect on cortical volume in the males, but
      not in females. CONCLUSIONS AND RELEVANCE: Sex differences in brain structure are
      large early in life. GA had sex-specific effects highlighting the importance
      evaluating sex effects in neurodevelopmental outcomes of premature infants.

PMID- 30279606
TI  - Direct Photochemical C-H Carboxylation of Aromatic Diamines with CO2 under
      Electron-Donor- and Base-free Conditions.
AB  - We report the photochemical carboxylation of o-phenylenedimamine in the absence
      of a base and an electron donor under an atmosphere of CO2, which afforded 2,3
      diaminobenzoic acid (DBA) in 28% synthetic yield and 0.22% quantum yield
      (Phi(%)). The synthetic yield of DBA in this reaction increased to 58% (Phi(%) =
      0.47) in the presence of Fe(II). The photochemical reaction described in this
      work provides an effective strategy to use light as the driving force for the
      direct carboxylation of organic molecules by CO2.

PMID- 30279609
TI  - Do inflammatory profiles explain ALS-FTD spectrum?

PMID- 30279610
TI  - Effect of pulsed electric field (PEF) treatment on sugarcane juice.
AB  - This study was carried out to evaluate the effect of PEF process using static
      treatment chamber on fresh sugarcane juice with and without addition of lemon and
      ginger with respect to microbial content, chemical properties, nutrient content
      and shelf life extention of the product. The fresh sugar cane juice without
      addition of lemon and ginger treated at different field strengths (30 kV cm-1 and
      50 kV cm-1) and different pulse numbers (150, 300) was initially investigated by
      storage at room temperature (31  degrees C) and refrigeration temperature (4 
      degrees C) for 30 days. The PEF effect on fresh sugar cane juice at room
      temperature and refrigerated temperature was compared with untreated sample (31 
      degrees C). At the end of the storage period samples treated at field strength 30
      kV cm-1, 150 pulses were found to be stable compared with untreated sample. The
      second experimental study of PEF process was done on fresh sugarcane juice with
      the addition of lemon and ginger for fourteen days at different electric field
      intensities (10 kV cm-1, 20 kV cm-1 and 30 kV cm-1) with the same pulse number
      (150 pulses) and stored 4  degrees C. Even better reduction of microbes was
      achieved with PEF treatment condition of field strength 20 kV cm-1, 150 pulses in
      the presence of lemon and ginger. The sensory attributes of untreated fresh
      sugarcane juice were maintained up to only two days, but for the PEF treated
      sample, shelf life was extened up to seven days. Further, addition of lemon and
      ginger in the PEF treated sugarcane juice doubled the shelf life up to fourteen
      days.

PMID- 30279611
TI  - Televised Medical Talk Shows: What They Recommend and the Evidence to Support
      Their Recommendations: A Prospective Observational Study.
AB  - Objective: To determine the quality of health recommendations and claims made on
      popular medical talk shows. Design: Prospective observational study. Setting:
      Mainstream television media. Sources: Internationally syndicated medical
      television talk shows that air daily (The Dr Oz Show and The Doctors).
      Interventions: Investigators randomly selected 40 episodes of each of The Dr Oz
      Show and The Doctors from early 2013 and identified and evaluated all
      recommendations made on each program. A group of experienced evidence reviewers
      independently searched for, and evaluated as a team, evidence to support 80
      randomly selected recommendations from each show. Main Outcomes Measures:
      Percentage of recommendations that are supported by evidence as determined by a
      team of experienced evidence reviewers. Secondary outcomes included topics
      discussed, the number of recommendations made on the shows, and the types and
      details of recommendations that were made. Results: We could find at least a case
      study or better evidence to support 54% (95% confidence interval 47% to 62%) of
      the 160 recommendations (80 from each show). For recommendations in The Dr Oz
      Show, evidence supported 46%, contradicted 15%, and was not found for 39%. For
      recommendations in The Doctors, evidence supported 63%, contradicted 14%, and was
      not found for 24%. Believable or somewhat believable evidence supported 33% of
      the recommendations on The Dr Oz Show and 53% on The Doctors. On average, The Dr
      Oz Show had 12 recommendations per episode and The Doctors 11. The most common
      recommendation category on The Dr Oz Show was dietary advice (39%) and on The
      Doctors was to consult a healthcare provider (18%). A specific benefit was
      described for 43% and 41% of the recommendations made on the shows respectively.
      The magnitude of benefit was described for 17% of the recommendations on The Dr
      Oz Show and 11% on The Doctors. Disclosure of potential conflicts of interest
      accompanied 0.4% of recommendations. Conclusions: Recommendations made on medical
      talk shows often lack adequate information on specific benefits or the magnitude
      of the effects of these benefits. Approximately half of the recommendations have
      either no evidence or are contradicted by the best available evidence. Potential
      conflicts of interest are rarely addressed. The public should be skeptical about
      recommendations made on medical talk shows.

PMID- 30279613
TI  - Missouri Medicine Annual Statement of Ownership, Management & Circulation.

PMID- 30279612
TI  - MSMA Members in the News.

PMID- 30279615
TI  - Zooplankton monitoring to contribute towards addressing global biodiversity
      conservation challenges.
AB  - Oceanographers have an increasing responsibility to ensure that the outcomes of
      scientific research are conveyed to the policy-making sphere to achieve
      conservation and sustainable use of marine biodiversity. Zooplankton monitoring
      projects have helped to increase our understanding of the processes by which
      marine ecosystems respond to climate change and other environmental variations,
      ranging from regional to global scales, and its scientific value is recognized in
      the contexts of fisheries, biodiversity and global change studies. Nevertheless,
      zooplankton data have rarely been used at policy level for conservation and
      management of marine ecosystems services. One way that this can be pragmatically
      and effectively achieved is via the development of zooplankton indicators, which
      could for instance contribute to filling in gaps in the suite of global
      indicators to track progress against the Aichi Biodiversity Targets of the United
      Nations Strategic Plan for Biodiversity 2010-2020. This article begins by
      highlighting how under-represented the marine realm is within the current suite
      of global Aichi Target indicators. We then examine the potential to develop
      global indicators for relevant Aichi Targets, using existing zooplankton
      monitoring data, to address global biodiversity conservation challenges.

PMID- 30279614
TI  - Intranuclear Mobility of Estrogen Receptor: Implication for Transcriptional
      Regulation.
AB  - The estrogen receptor (ER) is a ligand-dependent transcription factor that has
      two subtypes: ERalpha and ERbeta. ERs regulate transcription of estrogen
      responsive genes through interactions with multiple intranuclear components, such
      as cofactors and the nuclear matrix. Live cell imaging using fluorescent protein
      labeled ERs has revealed that ligand-activated ERs are highly mobile in the
      nucleus, with transient association with the DNA and nuclear matrix. Scaffold
      attachment factor B (SAFB) 1 and its paralogue, SAFB2, are nuclear matrix-binding
      proteins that negatively modulate ERalpha-mediated transcription. Expression of
      SAFB1 and SAFB2 reduces the mobility of ERalpha in the presence of ligand. This
      regulatory machinery is emerging as an epigenetic-like mechanism that alters
      transcriptional activity through control of intranuclear molecular mobility.

PMID- 30279616
TI  - The 13C method as a robust alternative to 14C-based measurements of primary
      productivity in the Mediterranean Sea.
AB  - Due to the increasing constraints on using the radioactive isotope 14C to measure
      primary productivity (14C-PP), we determined the surface carbon fixation rates in
      the Mediterranean Sea, using the alternative stable isotope 13C method (13C-PP).
      Rates obtained (13C-POCp) were compared with simultaneous 14C-POCp measurements
      in samples of different volumes (72 mL and 1.2 L). We also tested the variation
      of the percentage of dissolved primary production (PER), to the total
      productivity using organic and inorganic filters (14C method). 13C-POCp rates
      ranged from 0.4, in the Ionian basin, to 1.5 mgC m-3 h-1 in the Ligurian region.
      These results agreed with those found with the 14C-PP in 1.2-L samples (two
      sample t-test, t = 1.035, df = 22, P = 0.31). However, we found that 14C-POCp
      rates derived from 72-mL incubations were 46% lower than those measured with 13C
      PP. The discrepancy between large and small volume incubations was likely due to
      differences in the number of large phytoplankton cells within the community. PER
      values measured with silver membrane filters yielded similar results than those
      obtained using polycarbonate filters. Our findings showed that when the sample
      size is carefully chosen, the 13C-PP provide comparable results to 14C-PP even in
      waters of low productivity in the Mediterranean Sea.

PMID- 30279617
TI  - 5-N-Carboxyimino-6-N-chloroaminopyrimidine-2,4(3H)-dione as a hypochlorite
      specific oxidation product of uric acid.
AB  - Although uric acid is known to react with many reactive oxygen species, its
      specific oxidation products have not been fully characterized. We now report that
      5-N-carboxyimino-6-N-chloroaminopyrimidine-2,4(3H)-dione (CCPD) is a hypochlorite
      (ClO-)-specific oxidation product of uric acid. The yield of CCPD was 40-70%
      regardless of the rate of mixing of ClO- with uric acid. A previously reported
      product, allantoin (AL), was a minor product. Its yield (0-20%) decreased with
      decreasing rate of mixing of ClO- with uric acid, indicating that allantoin is
      less important in vivo. Kinetic studies revealed that the formation of CCPD
      required two molecules of ClO- per uric acid reacted. The identity of CCPD was
      determined from its molecular formula (C5H3ClN4O4) measured by LC/time-of-flight
      mass spectrometry and a plausible reaction mechanism. This assumption was
      verified by the fact that all mass fragments (m/z -173, -138, -113, and -110) fit
      with the chemical structure of CCPD and its tautomers. Isolated CCPD was stable
      at pH 6.0-8.0 at 37 degrees C for at least 6 h. The above results and the fact
      that uric acid is widely distributed in the human body at relatively high
      concentrations indicate that CCPD is a good marker of ClO- generation in vivo.

PMID- 30279618
TI  - Radical formation in individual aqueous solutions of some unsaturated fatty acids
      and in their mixtures.
AB  - This study examines oxidizability in individual aqueous solutions of oleic acid,
      linoleic acid, alpha-linolenic acid, gamma-linolenic acid and arachidonic acid,
      and in their mixtures. We used electron spin resonance (ESR), high performance
      liquid chromatography-electron spin resonance (HPLC-ESR) and high performance
      liquid chromatography-electron spin resonance-mass spectrometries (HPLC-ESR-MS).
      We detected 4-carboxybutyl radical derived from gamma-linolenic acid, ethyl and 7
      carboxyheptyl radicals derived from alpha-linolenic acid, and pentyl and 7
      carboxyheptyl radicals derived from linoleic acid. HPLC-ESR analyses for the
      individual aqueous solutions of linoleic acid, alpha-linolenic acid, gamma
      linolenic acid and arachidonic acid showed less radical form for polyunsaturated
      fatty acids with more double bonds. On the other hand, HPLC-ESR peak height of 4
      carboxybutyl radical, which form through hydrogen atom abstraction at the carbon
      close to the carboxy end, increased for linoleic acid/gamma-linolenic acid, alpha
      linolenic acid/gamma-linolenic acid, and gamma-linolenic acid/oleic acid mixtures
      compared to before mixing. Conversely, HPLC-ESR peak heights of ethyl, 7
      carboxyheptyl and pentyl radicals, which form through hydrogen atom abstraction
      at the carbons close to the methyl end, decreased for linoleic acid/alpha
      linolenic acid, linoleic acid/gamma-linolenic acid, linoleic acid/oleic acid,
      linoleic acid/arachidonic acid, alpha-linolenic acid/gamma-linolenic acid, and
      alpha-linolenic acid/oleic acid mixtures compared to before mixing.

PMID- 30279619
TI  - Localized hydroxyl radical generation at mmol/L and mol/L levels in water by
      photon irradiation.
AB  - The generation of localized hydroxyl radical (*OH) in aqueous samples by low
      linear energy transfer irradiation was investigated. Several concentrations of
      5,5-dimethyl-1-pyrroline-N-oxid solution (from 0.5 to 1,680 mmol/L) were prepared
      and irradiated with an identical dose of X-ray or gamma-ray. The density of *OH
      generation in aqueous solution was evaluated by the electron paramagnetic
      resonance spin-trapping technique using 5,5-dimethyl-1-pyrroline-N-oxid as an
      electron paramagnetic resonance spin-trapping agent. The relationship between the
      molecular density of 5,5-dimethyl-1-pyrroline-N-oxid in the samples and the
      concentration of 5,5-dimethyl-1-pyrroline-N-oxid-OH generated in the irradiated
      samples was analyzed. Two different characteristic linear trends were observed in
      the 5,5-dimethyl-1-pyrroline-N-oxid-OH/5,5-dimethyl-1-pyrroline-N-oxid plots,
      which suggested *OH generation in two fashions, i.e., mmol/L- and mol/L-level
      local concentrations. The dose, dose rate, and/or the energy of photon
      irradiation did not affect the shapes of the 5,5-dimethyl-1-pyrroline-N-oxid
      OH/5,5-dimethyl-1-pyrroline-N-oxid plots. Moreover, the addition of 5 mmol/L
      caffeine could cancel the contribution of mmol/L-level *OH generation, leaving a
      trace of mol/L-level *OH generation. Thus, the localized mmol/L- and mol/L-level
      generations of *OH, which were independent of experimental parameters such as
      dose, dose rate, and/or the energy of photon of low linear energy transfer
      radiation, were established.

PMID- 30279620
TI  - Luminal plant sterol promotes brush border membrane-to-lumen cholesterol efflux
      in the small intestine.
AB  - Plant sterols are used as food additives to reduce intestinal cholesterol
      absorption. They also increase fecal neutral sterol (FNS) excretion irrespective
      of the absorption inhibition. Intestine-mediated reverse cholesterol transport,
      or trans-intestinal cholesterol efflux (TICE), provides the major part of the
      increase of FNS excretion. However, it is unknown whether plant sterols stimulate
      TICE or not. We have shown previously that TICE can be evaluated by brush border
      membrane (BBM)-to-lumen cholesterol efflux. Thus, we examined whether luminal
      plant sterols stimulate BBM-to-lumen cholesterol efflux in the intestinal tract
      or not in mice. Cannulated upper jejunum that had been pre-labeled with orally
      given 3H-cholesterol, was flushed and perfused to collect 3H-cholesterol effluxed
      back into the lumen from the BBM to estimate the efflux efficiency. Adding 0.5
      mg/ml of plant sterols, but not cholesterol, in the perfusion solution doubled
      the efflux. Plant sterols enter the BBM and are effluxed back to the lumen
      rapidly, in which process cholesterol transporters in the BBM are involved. We
      thus speculate that phytosterols alter cholesterol flux in the BBM; thereby,
      increases BBM-to-lumen cholesterol efflux, resulting in the increased TICE.

PMID- 30279621
TI  - Dipeptidyl peptidase-4 inhibitors have adverse effects for the proliferation of
      human T cells.
AB  - Dipeptidyl peptidase-4 (DPP-4) is a critical molecule for the metabolism of
      incretins. In addition, DPP-4 is known as CD26, the receptor of T cells, and
      plays important role in activation of T cells. Recently, DPP-4 inhibitors (DPP4i)
      are reported to have several immunologic effects beyond glycemic control. DPP4i
      seem to have anti-inflammatory effects in patients with type 2 diabetes. This
      might be direct effects on T cells. However, the close mechanism is not clear. To
      evaluate the possibility, we performed ex vivo assays by using primarily human
      CD4+ T cells (CD4) and CD8+ T cells (CD8). We purified primary naive CD4 and CD8
      from human peripheral blood. Then, we evaluated the effect of DPP4i on the
      proliferation of naive T cells and the cytokine production in ex vivo
      experiments. The proliferation of CD4 and CD8 were suppressed by adding DPP4i in
      a dose dependent manner. However, DPP4i did not inhibit cytokine production from
      CD4. It was revealed by phospho-flow that the T cell receptor (TCR) signaling was
      attenuated in the presence of DPP4i. Taken together, DPP4i modulated TCR
      signaling, which contributed to attenuate the proliferation of CD4 and CD8. DPP4i
      have adverse effects for the proliferation of human T cells.

PMID- 30279622
TI  - Short-term replacement of starch with isomaltulose enhances both insulin
      dependent and -independent glucose uptake in rat skeletal muscle.
AB  - Dietary intervention for preventing postprandial increases in glucose level by
      replacing high-glycemic index (GI) carbohydrates with lower-GI carbohydrate has
      been proposed as a strategy for treating insulin-resistant metabolic disorders
      such as type II diabetes. In this study, we examined the effect of short-term
      replacement of starch with a low-GI disaccharide, isomaltulose, on insulin action
      in skeletal muscle. Male Wistar rats were fed isomaltulose for 12 h during their
      dark cycle. In isolated epitrochlearis muscle, insulin-induced glucose uptake was
      greater in tissue from rats treated with isomaltulose than from those treated
      with starch. This insulin-sensitizing effect occurred independently of changes
      visceral fat mass. To determine whether this sensitization was specific to
      insulin stimulation, we also measured glucose uptake in response to exercise. In
      isolated epitrochlearis muscles from rats that performed swimming exercise,
      exercise-induced glucose uptake was higher in isomaltulose-treated than starch
      treated animals. This amplification was associated with increased phosphorylation
      of exercise-induced AMP-activated protein kinase. In conclusion, our results
      demonstrate that short-term replacement of starch with isomaltulose enhances both
      insulin-dependent and -independent glucose uptake in isolated skeletal muscle.
      This transient replacement of carbohydrate with isomaltulose, together with
      exercise, represents a potentially effective approach for the management of
      insulin resistance.

PMID- 30279623
TI  - Nrf2-mediated anti-oxidant effects contribute to suppression of non-alcoholic
      steatohepatitis-associated hepatocellular carcinoma in murine model.
AB  - The exact mechanisms of hepatocellular carcinoma development in non-alcoholic
      steatohepatitis remain unclear. In this study, we used a new class of high-fat
      diet, which could induce hepatocellular carcinoma development without the use of
      general chemical carcinogens or knockout mice. We investigated the correlation
      between hepatocellular carcinoma and oxidative stress/anti-oxidant effects after
      depletion of the gut microbiota by treatment with antibiotics. Mice fed with the
      steatohepatitis-inducing high-fat diet (STHD-01) for 41 weeks developed
      hepatocellular carcinoma. Antibiotic-treatment in mice fed with STHD-01
      significantly depleted the gut microbiota and significantly ameliorated liver
      injury/histology. The tumor numbers of hepatocellular carcinoma were dramatically
      decreased by the antibiotics-treatment. We analyzed the factors involved in
      oxidative stress and anti-oxidant effects. Oxidative stress was elevated in mice
      fed with STHD-01, whereas some anti-oxidant factors were significantly elevated
      after antibiotics treatment. These results suggest that the gut microbiota is a
      key factor in improving oxidative stress induced by STHD-01 feeding.

PMID- 30279624
TI  - Increased oxidative stress and coenzyme Q10 deficiency in centenarians.
AB  - Aging populations are expanding worldwide, and the increasing requirement for
      nursing care has become a serious problem. Furthermore, successful aging is one
      of the highest priorities for individuals and societies. Centenarians are an
      informative cohort to study and inflammation has been found to be a key factor in
      predicting cognition and physical capabilities. Inflammation scores have been
      determined based on the levels of cytokines and C-reactive protein, however,
      serum antioxidants and lipid profiles have not been carefully examined. We found
      that the redox balance of coenzyme Q10 significantly shifted to the oxidized form
      and levels of strong antioxidants, such as ascorbic acid and unconjugated
      bilirubin, decreased significantly compared to 76-year-old controls, indicating
      an increased oxidative stress in centenarians. Levels of uric acid, an endogenous
      peroxynitrite scavenger, remained unchanged, suggesting that centenarians were
      experiencing moderate, chronic inflammatory conditions. Centenarians exhibited a
      hypocholesterolemic condition, while an increase in the ratio of free cholesterol
      to cholesterol esters suggests some impairment of liver function. Serum free
      fatty acids and monoenoic acid composition, markers of tissue oxidative damage,
      were significantly decreased in centenarians, indicating an impairment in the
      tissue repair system. Despite an elevation of the coenzyme Q10 binding protein
      Psap, serum total coenzyme Q10 levels decreased in centenarians. This suggests a
      serious deficiency of coenzyme Q10 in tissues, since tissue levels of coenzyme
      Q10 significantly decrease with age. Therefore, coenzyme Q10 supplementation
      could be beneficial for centenarians.

PMID- 30279625
TI  - Increased oxidative stress and renal injury in patients with sepsis.
AB  - Sepsis remains one of the leading causes of death in intensive care units. The
      early phase of sepsis is characterized by a massive formation of reactive oxygen
      and nitrogen species such as superoxide and nitric oxide. However, few
      comprehensive studies on plasma antioxidants have been reported. Increased
      oxidative stress was confirmed in sepsis patients (n = 18) at the time of
      hospitalization by a significant decrease in plasma ascorbic acid and a
      significant increase in the percentage of oxidized form of coenzyme Q10 in total
      coenzyme Q10 compared to age-matched healthy controls (n = 62). Tissue oxidative
      damage in patients was suggested by a significant decrease in polyunsaturated
      fatty acid contents and a significant increase in oleic acid contents in total
      free fatty acids. Thus, it is reasonable that plasma uric acid (end product of
      purines) would be significantly elevated. However, uric acid levels were
      continuously decreased during hospitalization for 7 days, indicating a continuous
      formation of peroxynitrite. A greater decrease in free cholesterol (FC) compared
      to cholesterol esters (CE) was observed. Thus, the FC/CE ratio significantly
      increased, suggesting deficiency of lecithin-cholesterol acyltransferase secreted
      from the liver. Plasma levels of prosaposin, a coenzyme Q10 binding protein,
      significantly decreased as compared to healthy controls. This may be correlated
      with renal injury in sepsis patients, since the kidney is thought to be a major
      secretor of prosaposin.

PMID- 30279626
TI  - Gender differences in LDL- and HDL-cholesterol subfractions in patients after the
      acute ischemic stroke and their association with oxidative stress markers.
AB  - The aim of our study was to examine gender differences of LDL- and HDL
      cholesterol subfractions in patients after the acute ischemic stroke with focus
      on small LDL and HDL subfractions, and their association with oxidative stress
      markers. In addition, we have monitored the 7-day effect of cholesterol-lowering
      drugs administered to patients after the acute ischemic stroke, on these
      subfractions. Eighty two stroke patients and 81 age matched controls were
      included in this study. Blood was collected from patients within 24 h after the
      stroke (group A) and re-examined at the 7-day follow-up (group B). We have found
      gender differences in LDL- and HDL-subfractions in stroke patients, lipid
      lowering drugs administered to acute ischemic stroke patients significantly
      reduced all measured parameters of lipoprotein profile. In the group A LDL1
      subfraction positively correlated with activity of antioxidant enzymes
      (superoxide dismutase, catalase, glutathione peroxidase) indicating a protective
      role of this subfraction. On the contrary, small HDL subfractions positively
      correlated with lipoperoxide levels and negatively with trolox equivalent
      antioxidant capacity in plasma suggesting a negative role of these subfractions.
      In this work we have confirmed the hypothesis of atherogenic properties of small
      HDL subfractions and anti-atherogenic properties of large LDL1-subfractions.

PMID- 30279627
TI  - Does discontinuation of antithrombotics affect the diagnostic yield of small
      bowel capsule endoscopy in patients demonstrating obscure gastrointestinal
      bleeding?
AB  - A large proportion of patients demonstrating obscure gastrointestinal bleeding
      (OGIB) are antithrombotic users and need to undergo small bowel capsule endoscopy
      (SBCE). We examined the effect of discontinuation of antithrombotics on the
      diagnostic yield of SBCE. Additionally, we assessed predictive factors associated
      with positive SBCE findings. Our study included 130 patients using
      antithrombotics who underwent SBCE for overt OGIB. The primary endpoint was the
      difference in the rate of positive SBCE findings between patients who continued
      and those who discontinued antithrombotics. Secondary endpoints were to
      investigate the effect of discontinuation of antithrombotics using a propensity
      score analysis, and to assess predictive factors associated with a positive SBCE.
      Among the 73 patients who continued use of antithrombotics, 36 (49.3%) patients
      demonstrated positive findings, while among the 57 patients who discontinued
      antithrombotics, 35 (61.4%) patients showed positive findings. Rates of positive
      SBCE findings didn't differ between the two groups. After we performed propensity
      score matching, discontinuation didn't affect the rate of positive SBCE findings.
      The lowest hemoglobin level was the only independent predictive factor associated
      with positive SBCE findings. In conclusion, discontinuation of antithrombotic
      therapy didn't affect the diagnostic yield of SBCE in patients presenting with
      overt OGIB.

PMID- 30279628
TI  - Sex differences in associations among metabolic syndrome, obesity, related
      biomarkers, and colorectal adenomatous polyp risk in a Japanese population.
AB  - To investigate sex differences in the associations among metabolic syndrome,
      obesity, adipose tissue-related biomarkers, and colorectal adenomatous polyps, a
      cross-sectional, multicenter study was conducted on 489 consecutive individuals
      who underwent their first colonoscopy at 3 hospitals. Plasma concentrations of
      adiponectin and leptin, as well as homeostatic model assessment of insulin
      resistance were also evaluated. The presence and number of adenomatous polyps,
      including advanced adenoma, were higher in men than in women. Metabolic syndrome
      was a risk factor for adenomatous polyps in both sexes. Large waist circumference
      was an independent risk factor for adenomatous polyps in men, and high BMI and
      large waist circumference were risk factors for adenomatous polyps in women.
      Interestingly, low BMI was associated with large adenomatous polyps (>=10 mm) and
      advanced adenoma, and waist-hip ratio was involved in proximal adenomatous polyp
      development only in women. In contrast, the highest quartile of leptin
      concentration had a 3.67-fold increased adenomatous polyp risk compared with the
      lowest quartile only in men. These results indicate that regarding colorectal
      pathogenesis, sex differences were identified in obesity but not in metabolic
      syndrome. Visceral obesity and a high serum leptin level may be risk factors for
      colorectal adenomatous polyp development in Japanese men.

PMID- 30279630
TI  - First report of partial albinism in the blue lobster Panulirusinflatus (Bouvier,
      1895) from the Mexican Pacific (Crustacea, Decapoda, Palinuridae).
AB  - The first case of partial albinism registered in the Mexican Pacific by the blue
      lobster Panulirusinflatus is presented. The specimen was collected on the
      southern coast of Jalisco know as Punta "El Estrecho". It constitutes one of the
      few registered cases of albinism in invertebrates from the Eastern Tropical
      Pacific.

PMID- 30279629
TI  - Estimation of perioperative invasiveness of colorectal endoscopic submucosal
      dissection evaluated by energy metabolism.
AB  - The aim of this study was to assess the perioperative invasiveness of endoscopic
      submucosal dissection for colorectal cancer quantitatively by using energy
      metabolism. In fifty-three patients who underwent endoscopic submucosal
      dissection for colorectal cancer, resting energy expenditure using an indirect
      calorimeter, body weight and basal energy expenditure using the Harris-Benedict
      equation before and after endoscopic submucosal dissection. Resting energy
      expenditure/body weight and resting energy expenditure/basal energy expenditure
      were 19.7 +/- 2.5 kcal/kg/day and 0.96 +/- 0.12 on the day of endoscopic
      submucosal dissection, whereas one day after the endoscopic submucosal dissection
      they increased to 21.0 +/- 2.9 kcal/kg/day and 1.00 +/- 0.13 (p<0.001 and p<0.05,
      respectively). The stress factor on the postoperative day 1 was computed as 1.06.
      The increase was lower comparing with that experienced for surgery, suggesting
      that the perioperative invasiveness of colorectal endoscopic submucosal
      dissection is lower in comparison to that during surgery. Furthermore, in spite
      of technical difficulty, stress factor of colorectal endoscopic submucosal
      dissection was approximately equal to that of gastric endoscopic submucosal
      dissection. (The study of the resting energy metabolism and stress factor using
      an indirect calorimeter in the perioperative period of endoscopic operation:
      UMIN000027135).

PMID- 30279632
TI  - Stigmellamultispicata Rociene. & Stonis, an Asian leafminer on Siberian elm, now
      widespread in eastern North America (Lepidoptera, Nepticulidae).
AB  - Stigmellamultispicata Rociene & Stonis, 2014, previously known from the single
      male holotype from Primorye, Russia, is reported as a new invasive species mining
      leaves of Siberian elm, Ulmuspumila L., in eastern North America. Both adults and
      leafmines have been reported from many sites as unidentified Nepticulidae since
      2010. Crucial for the identification was a match of the DNA barcode of a single
      larva collected on Ulmuspumila in Beijing with adults from North America. The
      single larva constitutes a new record for China. Stigmellamultispicata is closely
      related to the European S.ulmivora (Fologne, 1860), feeding likewise on Ulmus,
      but differs in details of external morphology and genitalia, particularly in the
      female, where S.multispicata has a remarkable elongated narrow ovipositor,
      suitable for oviposition in underside hairy leaf vein axils, where all mines
      start. In North America S.multispicata is the only Ulmus-feeding nepticulid with
      green larvae. Currently the species is known from USA: Illinois, Indiana, Iowa,
      Maryland, Massachusetts, Minnesota, New York, Ohio, Tennessee, Wisconsin, and
      Canada: Ontario and Quebec. In Sagaponack, on Long Island, New York, larvae have
      been reported to occur en masse on Siberian elms from at least two sites. The
      current distribution could be reconstructed thanks also to many online
      photographs from observation websites. The species is redescribed, with the first
      descriptions of female, larva, and leafmine, and compared with S.ulmivora, which
      is fully redescribed. The two native North American nepticulid Ulmus leafminers,
      S.apicialbella (Chambers, 1873) and Ectoedemiaulmella (Braun, 1912), are
      diagnosed and new provincial and state records are provided. A key to linear
      mines on Ulmus in North America is provided. We suspect that trade of live plants
      through nurseries played a role in the sudden spread of this invasive species.

PMID- 30279631
TI  - A first phylogenetic analysis reveals a new arboreal tarantula genus from South
      America with description of a new species and two new species of Tapinauchenius
      Ausserer, 1871 (Araneae, Mygalomorphae, Theraphosidae).
AB  - Based on molecular and morphological phylogenetic analyses a new genus of
      Theraphosidae is described, Pseudoclamoris gen. n. Tapinaucheniusgigas and
      Tapinaucheniuselenae are transferred to Pseudoclamoris and a new species of
      Pseudoclamoris from the Amazon Region is described: P.burgessi sp. n. Two new
      species of Tapinauchenius from the Caribbean are described: T.rasti sp. n. and
      T.polybotes sp. n. Tapinaucheniussubcaeruleus is considered a nomen dubium.
      Psalmopoeinae subfamily is diagnosed based on molecular and morphological
      phylogenies, and Pseudoclamoris gen. n. and Ephebopus Simon, 1892 are included. A
      taxonomic key for Psalmopoeinae genera Tapinauchenius, Pseudoclamoris,
      Psalmopoeus, and Ephebopus is provided.

PMID- 30279633
TI  - BumbleKey: an interactive key for the identification of bumblebees of Italy and
      Corsica (Hymenoptera, Apidae).
AB  - BumbleKey is a matrix-based, interactive key to all 45 species of bumblebees of
      Italy and Corsica. The key allows to identify adult males and females (queens and
      workers) using morphological characters. The key is published online, open
      access, at http://www.interactive-keys.eu/bumblekey/default.aspx.

PMID- 30279634
TI  - Chiropteran diversity in the peripheral areas of the Maduru-Oya National Park in
      Sri Lanka: insights for conservation and management.
AB  - In Sri Lanka, there are 31 species of bats distributed from lowlands to
      mountains. To document bat diversity and their habitat associations, 58 roosting
      sites in Maduru-Oya National Park periphery were surveyed. Fifteen bat species
      were recorded occupying 16 different roosting sites in this area. Among all the
      species recorded, Rhinolophusrouxii was the most abundant species per roosting
      site whereas Kerivoulapicta was the least abundant. A road-kill specimen similar
      to genus Phoniscus was found during the survey, a genus so far only documented in
      Southeast Asia and Australasia. Although our study area provided habitats for a
      diverse chiropteran community, the colony size per roost was remarkably low.
      Although our study area is supposedly a part of the park's buffer zone, many
      anthropogenic activities are threatening the bat community: felling large trees,
      slash-and-burn agriculture, excessive use of agrochemicals, vengeful killing, and
      subsidized predation. We strongly recommend adoption of wildlife-friendly
      sustainable land management practices in the buffer zone such as forest
      gardening, agroforestry (alley cropping, mixed-cropping), and integrated farming.
      Bat conservation in this region should take a landscape-scale conservation
      approach which includes Maduru-Oya National Park and other surrounding protected
      areas into a regional conservation network. Extents of undisturbed wilderness are
      dramatically declining in Sri Lanka; thus, future conservation efforts must be
      retrofitted into anthropocentric multiuse landscapes and novel ecosystems like
      areas surrounding Maduru-Oya National Park.

PMID- 30279635
TI  - Sample Entropy on Multidistance Signal Level Difference for Epileptic EEG
      Classification.
AB  - Epilepsy is a disorder of the brain's nerves as a result of excessive brain cell
      activity. It is generally characterized by the recurrent unprovoked seizures.
      This neurological abnormality can be detected and evaluated using
      Electroencephalogram (EEG) signal. Many algorithms have been applied to achieve
      high performance for the EEG classification of epileptic. However, the complexity
      and randomness of EEG signals become a challenge to researchers in applying the
      appropriate algorithms. In this research, sample entropy on Multidistance Signal
      Level Difference (MSLD) was applied to obtain the characteristic of EEG signals,
      especially towards the epilepsy patients. The test was performed on three classes
      of EEG data: EEG signals of epilepsy patient in ictal (seizure), interictal
      conditions (occurring between seizures) and normal EEG signals from healthy
      subjects with a closed eye condition. In this study, classification and
      verification were done using the Support Vector Machine (SVM) method. Through the
      5-fold cross-validation, experimental results showed the highest accuracy of
      97.7%.

PMID- 30279636
TI  - Understanding and Managing IBS and CIC in the Primary Care Setting.

PMID- 30279637
TI  - Serial electron crystallography for structure determination and phase analysis of
      nanocrystalline materials.
AB  - Serial electron crystallography has been developed as a fully automated method to
      collect diffraction data on polycrystalline materials using a transmission
      electron microscope. This enables useful data to be collected on materials that
      are sensitive to the electron beam and thus difficult to measure using the
      conventional methods that require long exposure of the same crystal. The data
      collection strategy combines goniometer translation with electron beam shift,
      which allows the entire sample stage to be probed. At each position of the
      goniometer, the locations of the crystals are identified using image recognition
      techniques. Diffraction data are then collected on each crystal using a quasi
      parallel focused beam with a predefined size (usually 300-500 nm). It is shown
      that with a fast and sensitive Timepix hybrid pixel area detector it is possible
      to collect diffraction data of up to 3500 crystals per hour. These data can be
      indexed using a brute-force forward-projection algorithm. Results from several
      test samples show that 100-200 frames are enough for structure determination
      using direct methods or dual-space methods. The large number of crystals examined
      enables quantitative phase analysis and automatic screening of materials for
      known and unknown phases.

PMID- 30279638
TI  - Glassy carbon, NIST Standard Reference Material (SRM 3600): hydrogen content,
      neutron vibrational density of states and heat capacity.
AB  - Commercial glassy carbon plates being used as absolute intensity calibration
      standards in small-angle X-ray scattering applications (NIST SRM 3600) have been
      characterized in several recent publications. This contribution adds to the
      characterization by measuring the hydrogen content of a plate to be (4.8 +/- 0.2)
      * 10-4 (mol H)/(mol C), and by measuring the vibrational spectrum by neutron
      inelastic scattering. The spectrum bears a strong resemblance to published
      measurements on graphite, allowing the identification of several spectral
      features. The measured spectrum is used to calculate the heat capacity of low
      hydrogen-content glassy carbon for comparison with measurements reported here
      from 20 to 295 K.

PMID- 30279639
TI  - Stacking faults in beta-Ga2O3 crystals observed by X-ray topography.
AB  - Planar defects in -oriented beta-Ga2O3 wafers were studied using X-ray
      topography. These planar defects were rectangular with dimensions of 50-150 um,
      and the X-ray topography analysis revealed that they were stacking faults (SFs)
      enclosed by a single partial dislocation loop on the plane. The SF formation was
      found to be supported by a unique structural feature of the plane as a slip
      plane; the plane consists of close-packed octahedral Ga and O layers, allowing
      slips to form SFs. Vacancy arrays along the b axis in the octahedral Ga layer
      reduce the self-energy of the edge component in the partial dislocation extending
      along the b axis. It is speculated that the SFs occur during the crystal growth
      process for unknown reasons and then recover owing to elastic instability after
      initially increasing in size as crystal growth proceeds. Based on this analysis,
      a structural model for the SFs is proposed.

PMID- 30279640
TI  - Model-free classification of X-ray scattering signals applied to image
      segmentation.
AB  - In most cases, the analysis of small-angle and wide-angle X-ray scattering (SAXS
      and WAXS, respectively) requires a theoretical model to describe the sample's
      scattering, complicating the interpretation of the scattering resulting from
      complex heterogeneous samples. This is the reason why, in general, the analysis
      of a large number of scattering patterns, such as are generated by time-resolved
      and scanning methods, remains challenging. Here, a model-free classification
      method to separate SAXS/WAXS signals on the basis of their inflection points is
      introduced and demonstrated. This article focuses on the segmentation of scanning
      SAXS/WAXS maps for which each pixel corresponds to an azimuthally integrated
      scattering curve. In such a way, the sample composition distribution can be
      segmented through signal classification without applying a model or previous
      sample knowledge. Dimensionality reduction and clustering algorithms are employed
      to classify SAXS/WAXS signals according to their similarity. The number of
      clusters, i.e. the main sample regions detected by SAXS/WAXS signal similarity,
      is automatically estimated. From each cluster, a main representative SAXS/WAXS
      signal is extracted to uncover the spatial distribution of the mixtures of phases
      that form the sample. As examples of applications, a mudrock sample and two
      breast tissue lesions are segmented.

PMID- 30279641
TI  - Calibration of rotation axes for multi-axis goniometers in macromolecular
      crystallography.
AB  - The installation of multi-axis goniometers such as the ESRF/EMBL miniKappa
      goniometer system has allowed the increased use of sample reorientation in
      macromolecular crystallography. Old and newly appearing data collection methods
      require precision and accuracy in crystal reorientation. The proper use of such
      multi-axis systems has necessitated the development of rapid and easy to perform
      methods for establishing and evaluating device calibration. A new diffraction
      based method meeting these criteria has been developed for the calibration of the
      motors responsible for rotational motion. This method takes advantage of crystal
      symmetry by comparing the orientations of a sample rotated about a given axis and
      checking that the magnitude of the real rotation fits the calculated angle
      between these two orientations. Hence, the accuracy and precision of rotational
      motion can be assessed. This rotation calibration procedure has been performed on
      several beamlines at the ESRF and other synchrotrons. Some resulting data are
      presented here for reference.

PMID- 30279642
TI  - Effects of multiple scattering encountered for various small-angle scattering
      model functions.
AB  - In small-angle scattering theory and data modeling, it is generally assumed that
      each scattered ray - photon or neutron - is only scattered once on its path
      through the sample. This assumption greatly simplifies the interpretation of the
      data and is valid in many cases. However, it breaks down under conditions of high
      scattering power, increasing with sample concentration, scattering contrast,
      sample path length and ray wavelength. For samples with a significant scattering
      power, disregarding multiple scattering effects can lead to erroneous conclusions
      on the structure of the investigated sample. In this paper, the impact of
      multiple scattering effects on different types of scattering pattern are
      determined, and methods for assessing and addressing them are discussed,
      including the general implementation of multiple scattering effects in structural
      model fits. The modification of scattering patterns by multiple scattering is
      determined for the sphere scattering function and the Gaussian function, as well
      as for different Sabine-type functions, including the Debye-Andersen-Brumberger
      (DAB) model and the Lorentzian scattering function. The calculations are
      performed using the semi-analytical convolution method developed by Schelten &
      Schmatz [J. Appl. Cryst. (1980 ?). 13, 385-390], facilitated by analytical
      expressions for intermediate functions, and checked with Monte Carlo simulations.
      The results show how a difference in the shape of the scattering function plotted
      versus momentum transfer q results in different multiple scattering effects at
      low q, where information on the particle mass and radius of gyration is
      contained.

PMID- 30279643
TI  - Variations in morphological traits of bermudagrass and relationship with soil and
      climate along latitudinal gradients.
AB  - Background: This complex environmental heterogeneity coupled with the long
      standing history offers scenario suitable for and favoring the evolution and
      existence of variation of morphological traits. Methods: In this study, we
      measured 10 morphological traits of 310 Cynodon dactylon individuals sampled at
      16 different locations along latitudinal gradients between 22 degrees 35'N and 36
      degrees 18'N to reveal phenotypic plasticity influenced by latitude. In addition,
      the relationships between morphological variation and soil nutrient and climate
      factors were analyzed. Results: Analysis of variance, divesity examination and
      Mantel correlation test detected a significant effect of latitude on
      morphological traits. Cluster analysis and principal component analysis clearly
      separated the selected populations into four groups according to latitude. Larger
      morphological sizes of C. dactylon appeared at the low- and high-latitude
      regions. Correlation analysis indicated that high morphological variations were
      significantly correlated with climate factors and soil nutrient. Conclusion: This
      study suggests morphological variation of wild bermudagrass is greatly influenced
      by latitude as well as soil and climate, which could be useful resources for
      genetic studies and evolution.

PMID- 30279644
TI  - Long-read sequencing identified a causal structural variant in an exome-negative
      case and enabled preimplantation genetic diagnosis.
AB  - Background: For a proportion of individuals judged clinically to have a recessive
      Mendelian disease, only one heterozygous pathogenic variant can be found from
      clinical whole exome sequencing (WES), posing a challenge to genetic diagnosis
      and genetic counseling. One possible reason is the limited ability to detect
      disease causal structural variants (SVs) from short reads sequencing
      technologies. Long reads sequencing can produce longer reads (typically 1000 bp
      or longer), therefore offering greatly improved ability to detect SVs that may be
      missed by short-read sequencing. Results: Here we describe a case study, where
      WES identified only one heterozygous pathogenic variant for an individual
      suspected to have glycogen storage disease type Ia (GSD-Ia), which is an
      autosomal recessive disease caused by bi-allelic mutations in the G6PC gene.
      Through Nanopore long-read whole-genome sequencing, we identified a 7.1 kb
      deletion covering two exons on the other allele, suggesting that complex
      structural variants (SVs) may explain a fraction of cases when the second
      pathogenic allele is missing from WES on recessive diseases. Both breakpoints of
      the deletion are within Alu elements, and we designed Sanger sequencing and
      quantitative PCR assays based on the breakpoints for preimplantation genetic
      diagnosis (PGD) for the family planning on another child. Four embryos were
      obtained after in vitro fertilization (IVF), and an embryo without deletion in
      G6PC was transplanted after PGD and was confirmed by prenatal diagnosis,
      postnatal diagnosis, and subsequent lack of disease symptoms after birth.
      Conclusions: In summary, we present one of the first examples of using long-read
      sequencing to identify causal yet complex SVs in exome-negative patients, which
      subsequently enabled successful personalized PGD.

PMID- 30279645
TI  - Variable Neural Contributions to Explicit and Implicit Learning During Visuomotor
      Adaptation.
AB  - We routinely make fine motor adjustments to maintain optimal motor performance.
      These adaptations have been attributed to both implicit, error-based mechanisms,
      and explicit, strategy-based mechanisms. However, little is known about the
      neural basis of implicit vs. explicit learning. Here, we aimed to use anodal
      transcranial direct current stimulation (tDCS) to probe the relationship between
      different brain regions and learning mechanisms during a visuomotor adaptation
      task in humans. We hypothesized that anodal tDCS over the cerebellum (CB) should
      increase implicit learning while anodal tDCS over the dorsolateral prefrontal
      cortex (dlPFC), a region associated with higher-level cognition, should
      facilitate explicit learning. Using a horizontal visuomotor adaptation task that
      measures explicit/implicit contributions to learning (Taylor et al., 2014), we
      found that dlPFC stimulation significantly improved performance compared to the
      other groups, and weakly increased explicit learning. However, CB stimulation had
      no effects on either target error or implicit learning. Previous work showed
      variable CB stimulation effects only on a vertical visuomotor adaptation task
      (Jalali et al., 2017), so in Experiment 2, we conducted the same study using a
      vertical context to see if we could find effects of CB stimulation. We found only
      weak effects of CB stimulation on target error and implicit learning, and now the
      dlPFC effect did not replicate. To resolve this discrepancy, in Experiment 3, we
      examined the effect of context (vertical vs. horizontal) on implicit and explicit
      contributions and found that individuals performed significantly worse and used
      greater implicit learning in the vertical screen condition compared to the
      horizontal screen condition. Across all experiments, however, there was high
      inter-individual variability, with strong influences of a few individuals,
      suggesting that these effects are not consistent across individuals. Overall,
      this work provides preliminary support for the idea that different neural regions
      can be engaged to improve visuomotor adaptation, but shows that each region's
      effects are highly context-dependent and not clearly dissociable from one
      another. This holds implications especially in neurorehabilitation, where an
      intact neural region could be engaged to potentially compensate if another region
      is impaired. Future work should examine factors influencing interindividual
      variability during these processes.

PMID- 30279646
TI  - Inhibition of DNA Methylation With Zebularine Alters Lipopolysaccharide-Induced
      Sickness Behavior and Neuroinflammation in Mice.
AB  - Activity of DNA methyltransferases (DNMTs), the enzymes that catalyze DNA
      methylation, is dynamically regulated in the brain. DNMT inhibitors alter DNA
      methylation globally in the brain and at individual neural plasticity-associated
      genes, but how DNMT inhibitors centrally influence lipopolysaccharide (LPS)
      induced neuroinflammation is not known. We investigated whether the DMNT
      inhibitor, zebularine, would alter sickness behavior, DNA methylation of the Il
      1beta promoter and expression of inflammatory genes in hippocampus and microglia.
      Contrary to our hypothesis that zebularine may exaggerate LPS-induced sickness
      response and neuroinflammation, adult mice treated with an
      intracerebroventricular (ICV) injection of zebularine prior to LPS had
      surprisingly faster recovery of burrowing behavior compared to mice treated with
      LPS. Further, genes of inflammatory markers, epigenetic regulators, and the
      microglial sensory apparatus (i.e., the sensome) were differentially expressed by
      zebularine alone or in combination with LPS. Bisulfite pyrosequencing revealed
      that ICV zebularine led to decreased DNA methylation of two CpG sites near the Il
      1beta proximal promoter alone or in combination with LPS. Zebularine treated mice
      still exhibited decreased DNA methylation 48 h after treatment when LPS-induced
      sickness behavior as well as hippocampal and microglial gene expression were
      similar to control mice. Taken together, these data suggest that decreased DNA
      methylation, specifically of the Il-1beta promoter region, with a DNMT inhibitor
      in the brain disrupts molecular mechanisms of neuroinflammation.

PMID- 30279647
TI  - Presynaptic mGlu1 Receptors Control GABAB Receptors in an Antagonist-Like Manner
      in Mouse Cortical GABAergic and Glutamatergic Nerve Endings.
AB  - Mouse cortical GABAergic synaptosomes possess presynaptic inhibitory GABAB
      autoreceptors. Accordingly, (+/-)baclofen (3 MUM) inhibits in a CGP53423
      sensitive manner the 12 mM KCl-evoked release of preloaded [3H]GABA. Differently,
      the existence of presynaptic release-regulating metabotropic glutamate type 1
      (mGlu1) heteroreceptors in these terminals is still matter of discussion,
      although confocal microscopy unveiled the existence of mGlu1alpha with GABAB1 or
      GABAB2 proteins in cortical VGAT-positive synaptosomes. The group I mGlu agonist
      3,5-DHPG failed to modify on its own the 12 mM KCl-evoked [3H]GABA exocytosis
      from cortical nerve endings, but, when added concomitantly to the GABAB agonist,
      it significantly reduced the 3 MUM (+/-)baclofen-induced inhibition of [3H]GABA
      exocytosis. Conversely, the mGlu1 antagonist LY367385 (0.03-1 MUM), inactive on
      its own on GABA exocytosis, amplified the 3 MUM (+/-)baclofen-induced inhibition
      of [3H]GABA overflow. The ( +/- )baclofen-induced inhibition of [3H]GABA
      exocytosis was more pronounced in cortical synaptosomes from Grm1crv4/crv4 mice,
      which bear a spontaneous mutation of the Grm1 gene leading to the functional
      inactivation of the mGlu1 receptor. Inasmuch, the expression of GABAB2 receptor
      protein in cortical synaptosomal lysates from Grm1crv4/crv4 mice was increased
      when compared to controls. Altogether, these observations seem best interpreted
      by assuming that mGlu1 coexist with GABAB receptors in GABAergic cortical
      synaptosomes, where they control GABA receptors in an antagonist-like manner. We
      then asked whether the mGlu1-mediated control of GABAB receptors is restricted to
      GABAergic terminals, or if it occurs also in other subpopulations of nerve
      endings. Release-regulating GABAB receptors also exist in glutamatergic nerve
      endings. (+/-)baclofen (1 MUM) diminished the 12 mM KCl-evoked [3H]D-aspartate
      overflow. Also in these terminals, the concomitant presence of 1 MUM LY367385,
      inactive on its own, significantly amplified the inhibitory effect exerted by (+/
      )baclofen on [3H]D-aspartate exocytosis. Confocal microscopy confirmed the
      colocalization of mGlu1 with GABAB1 and GABAB2 labeling in vesicular glutamate
      type1 transporter-positive particles. Our results support the conclusion that
      mGlu1 receptors modulate in an antagonist-like manner presynaptic release
      regulating GABAB receptors. This receptor-receptor interaction could be
      neuroprotective in central disease typified by hyperglutamatergicity.

PMID- 30279648
TI  - Drug Screening Identifies Sigma-1-Receptor as a Target for the Therapy of VWM
      Leukodystrophy.
AB  - Vanishing white matter (VWM) disease is an autosomal genetic leukodystrophy
      caused by mutations in subunits of eukaryotic translation initiation factor 2B
      (eIF2B). The clinical symptoms exhibit progressive loss of white matter in both
      hemispheres of the brain, accompanied by motor functions deterioration,
      neurological deficits, and early death. To date there is no treatment for VWM
      disease. The aim of this work was to expedite rational development of a
      therapeutic opportunity. Our approach was to design a computer-aided strategy for
      an efficient and reliable screening of drug-like molecules; and to use primary
      cultures of fibroblasts isolated from the Eif2b5R132H/R132H VWM mouse model for
      screening. The abnormal mitochondria content phenotype of the mutant cells was
      chosen as a read-out for a simple cell-based fluorescent assay to assess the
      effect of the tested compounds. We obtained a hit rate of 0.04% (20 hits out of
      50,000 compounds from the selected library). All primary hits decreased
      mitochondria content and brought it closer to WT levels. Structural similarities
      between our primary hits and other compounds with known targets allowed the
      identification of three putative cellular pathways/targets: 11beta-hydroxysteroid
      dehydrogenase type 1, Sonic hedgehog (Shh), and Sigma-1-Receptor (S1R). In
      addition to initial experimental indication of Shh pathway impairment in VWM
      mouse brains, the current study provides evidence that S1R is a relevant target
      for pharmaceutical intervention for potential treatment of the disease.
      Specifically, we found lower expression level of S1R protein in fibroblasts,
      astrocytes, and whole brains isolated from Eif2b5R132H/R132H compared to WT mice,
      and confirmed that one of the hits is a direct binder of S1R, acting as agonist.
      Furthermore, we provide evidence that treatment of mutant mouse fibroblasts and
      astrocytes with various S1R agonists corrects the functional impairments of their
      mitochondria and prevents their need to increase their mitochondria content for
      compensation purposes. Moreover, S1R activation enhances the survival rate of
      mutant cells under ER stress conditions, bringing it to WT levels. This study
      marks S1R as a target for drug development toward treatment of VWM disease.
      Moreover, it further establishes the important connection between white matter
      well-being and S1R-mediated proper mitochondria/ER function.

PMID- 30279650
TI  - Spontaneous Neural Activity in the Superior Temporal Gyrus Recapitulates Tuning
      for Speech Features.
AB  - Background: Numerous studies have demonstrated that individuals exhibit
      structured neural activity in many brain regions during rest that is also
      observed during different tasks, however it is still not clear whether and how
      resting state activity patterns may relate to underlying tuning for specific
      stimuli. In the posterior superior temporal gyrus (STG), distinct neural activity
      patterns are observed during the perception of specific linguistic speech
      features. We hypothesized that spontaneous resting-state neural dynamics of the
      STG would be structured to reflect its role in speech perception, exhibiting an
      organization along speech features as seen during speech perception. Methods:
      Human cortical local field potentials were recorded from the superior temporal
      gyrus (STG) in 8 patients undergoing surgical treatment of epilepsy. Signals were
      recorded during speech perception and rest. Patterns of neural activity (high
      gamma power: 70-150 Hz) during rest, extracted with spatiotemporal principal
      component analysis, were compared to spatiotemporal neural responses to speech
      features during perception. Hierarchical clustering was applied to look for
      patterns in rest that corresponded to speech feature tuning. Results: Significant
      correlations were found between neural responses to speech features (sentence
      onsets, consonants, and vowels) and the spontaneous neural activity in the STG.
      Across subjects, these correlations clustered into five groups, demonstrating
      tuning for speech features-most robustly for acoustic onsets. These correlations
      were not seen in other brain areas, or during motor and spectrally-rotated speech
      control tasks. Conclusions: In this study, we present evidence that the RS
      structure of STG activity robustly recapitulates its stimulus-evoked response to
      acoustic onsets. Further, secondary patterns in RS activity appear to correlate
      with stimulus-evoked responses to speech features. The role of these spontaneous
      spatiotemporal activity patterns remains to be elucidated.

PMID- 30279649
TI  - Eight Weddings and Six Funerals: An fMRI Study on Autobiographical Memories.
AB  - "Autobiographical memory" (AM) refers to remote memories from one's own life.
      Previous neuroimaging studies have highlighted that voluntary retrieval processes
      from AM involve different forms of memory and cognitive functions. Thus, a
      complex and widespread brain functional network has been found to support AM. The
      present functional magnetic resonance imaging (fMRI) study used a multivariate
      approach to determine whether neural activity within the AM circuit would
      recognize memories of real autobiographical events, and to evaluate individual
      differences in the recruitment of this network. Fourteen right-handed females
      took part in the study. During scanning, subjects were presented with sentences
      representing a detail of a highly emotional real event (positive or negative) and
      were asked to indicate whether the sentence described something that had or had
      not really happened to them. Group analysis showed a set of cortical areas able
      to discriminate the truthfulness of the recalled events: medial prefrontal
      cortex, posterior cingulate/retrosplenial cortex, precuneus, bilateral angular,
      superior frontal gyri, and early visual cortical areas. Single-subject results
      showed that the decoding occurred at different time points. No differences were
      found between recalling a positive or a negative event. Our results show that the
      entire AM network is engaged in monitoring the veracity of AMs. This process is
      not affected by the emotional valence of the experience but rather by individual
      differences in cognitive strategies used to retrieve AMs.

PMID- 30279651
TI  - Altered Functional Connectivity in Resting State Networks in Tourette's Disorder.
AB  - Introduction: Brain regions are anatomically and functionally interconnected in
      order to facilitate important functions like cognition and movement. It remains
      incompletely understood how brain connectivity contributes to the pathophysiology
      of Tourette's disorder (TD). By using resting-state functional MRI, we aimed to
      identify alterations in the default mode network (DMN), frontal-parietal network
      (FPN), sensori-motor network (SMN), and salience network (SN) in TD compared with
      healthy control (HC) subjects. Method: In 23 adult TD patients and 22 HC, 3T-MRI
      resting-state scans were obtained. Independent component analysis was performed
      comparing TD and HC to investigate connectivity patterns within and between
      resting-state networks. Results: TD patients showed higher involvement of the
      dorsal medial prefrontal cortex in the connectivity of the DMN and less
      involvement of the inferior parietal cortex in the connectivity of the FPN when
      compared to HC. Moreover, TD patients showed a stronger coupling between DMN and
      left FPN than HC. Finally, in TD patients, functional connectivity within DMN
      correlated negatively with tic severity. Conclusion: We tentatively interpret the
      increased functional connectivity within DMN in TD patients as compensatory to
      the lower functional connectivity within left FPN. The stronger coupling between
      DMN and left FPN, together with the finding that higher DMN intrinsic
      connectivity is associated with lower tic severity would indicate that DMN is
      recruited to exert motor inhibition.

PMID- 30279654
TI  - Editorial: Synaptic Assembly and Neural Circuit Development.

PMID- 30279652
TI  - Common and Unique Neural Systems Underlying the Working Memory Maintenance of
      Emotional vs. Bodily Reactions to Affective Stimuli: The Moderating Role of Trait
      Emotional Awareness.
AB  - Many leading theories suggest that the neural processes underlying the experience
      of one's own emotional reactions partially overlap with those underlying bodily
      perception (i.e., interoception, somatosensation, and proprioception). However,
      the goal-directed maintenance of one's own emotions in working memory (EWM) has
      not yet been compared to WM maintenance of one's own bodily reactions (BWM). In
      this study, we contrasted WM maintenance of emotional vs. bodily reactions to
      affective stimuli in 26 healthy individuals while they underwent functional
      magnetic resonance imaging. Specifically, we examined the a priori hypothesis
      that individual differences in trait emotional awareness (tEA) would lead to
      greater differences between these two WM conditions within medial prefrontal
      cortex (MPFC). We observed that MPFC activation during EWM (relative to BWM) was
      positively associated with tEA. Whole-brain analyses otherwise suggested
      considerable similarity in the neural activation patterns associated with EWM and
      BWM. In conjunction with previous literature, our findings not only support a
      central role of body state representation/maintenance in EWM, but also suggest
      greater engagement of MPFC-mediated conceptualization processes during EWM in
      those with higher tEA.

PMID- 30279653
TI  - Optimal Localist and Distributed Coding of Spatiotemporal Spike Patterns Through
      STDP and Coincidence Detection.
AB  - Repeating spatiotemporal spike patterns exist and carry information. Here we
      investigated how a single spiking neuron can optimally respond to one given
      pattern (localist coding), or to either one of several patterns (distributed
      coding, i.e., the neuron's response is ambiguous but the identity of the pattern
      could be inferred from the response of multiple neurons), but not to random
      inputs. To do so, we extended a theory developed in a previous paper (Masquelier,
      2017), which was limited to localist coding. More specifically, we computed
      analytically the signal-to-noise ratio (SNR) of a multi-pattern-detector neuron,
      using a threshold-free leaky integrate-and-fire (LIF) neuron model with non
      plastic unitary synapses and homogeneous Poisson inputs. Surprisingly, when
      increasing the number of patterns, the SNR decreases slowly, and remains
      acceptable for several tens of independent patterns. In addition, we investigated
      whether spike-timing-dependent plasticity (STDP) could enable a neuron to reach
      the theoretical optimal SNR. To this aim, we simulated a LIF equipped with STDP,
      and repeatedly exposed it to multiple input spike patterns, embedded in equally
      dense Poisson spike trains. The LIF progressively became selective to every
      repeating pattern with no supervision, and stopped discharging during the Poisson
      spike trains. Furthermore, tuning certain STDP parameters, the resulting pattern
      detectors were optimal. Tens of independent patterns could be learned by a single
      neuron using a low adaptive threshold, in contrast with previous studies, in
      which higher thresholds led to localist coding only. Taken together these results
      suggest that coincidence detection and STDP are powerful mechanisms, fully
      compatible with distributed coding. Yet we acknowledge that our theory is limited
      to single neurons, and thus also applies to feed-forward networks, but not to
      recurrent ones.

PMID- 30279655
TI  - Cognitive Reserve Factors in a Developing Country: Education and Occupational
      Attainment Lower the Risk of Dementia in a Sample of Lebanese Older Adults.
AB  - Background: Dementia secondary to neurodegenerative diseases is prevalent among
      older adults and leads to social, psychological and economic burden on patients,
      caregivers and the community as a whole. Cognitive reserve factors such as
      education, and mental stimulation among others were hypothesized to contribute to
      the resilience against age-related cognitive impairment. Educational attainment,
      occupation complexity, physical activity, and leisure activity are explored in
      the context of protecting the older adults' cognitive function. We investigated
      the cognitive reserve effect on dementia, cognitive decline and impairment, and
      global cognitive function. Methods: This study is a secondary analysis of data
      from a cross-sectional, community-based cohort study that aimed at investigating
      factors associated with dementia and their prevalence. The sample was of 508
      community based older adults in Lebanon, aged 65 years and above in addition to
      502 informants designated by these older adults. Older adults and informants
      answered structured questionnaires administered by interviewers, as well as a
      physical assessment and a neurological examination. Older adults were diagnosed
      for dementia. Global cognitive function, depression, and cognitive decline were
      assessed. Results: Older adults with dementia had lower levels of education, and
      attained lower occupational complexity. Factors such as high education, complex
      occupation attainment, and leisure activity, significantly predicted better
      global cognitive function. An older adult who attained high education levels or
      high complexity level occupation was 7.1 or 4.6 times more likely to have better
      global cognitive function than another who attained lower education or complexity
      level occupation respectively. Conclusion: These results suggest that cognitive
      reserve factors ought to be taken into consideration clinically during the course
      of dementia diagnosis and when initiating community-based preventive strategies.

PMID- 30279656
TI  - Cerebral Blood Flow and Cognitive Functioning in a Community-Based, Multi-Ethnic
      Cohort: The SABRE Study.
AB  - Introduction: Lower cerebral blood flow (CBF) is associated with cardiovascular
      disease and vascular risk factors, and is increasingly acknowledged as an
      important contributor to cognitive decline and dementia. In this cross-sectional
      study, we examined the association between CBF and cognitive functioning in a
      community-based, multi-ethnic cohort. Methods: From the SABRE (Southall and Brent
      Revisited) study, we included 214 European, 151 South Asian and 87 African
      Caribbean participants (71 +/- 5 years; 39%F). We used 3T pseudo-continuous
      arterial spin labeling to estimate whole-brain, hematocrit corrected CBF. We
      measured global cognition and three cognitive domains (memory, executive
      functioning/attention and language) with a neuropsychological test battery.
      Associations were investigated using linear regression analyses, adjusted for
      demographic variables, vascular risk factors and MRI measures. Results: Across
      groups, we found an association between higher CBF and better performance on
      executive functioning/attention (standardized beta [stbeta] = 0.11, p < 0.05).
      Stratification for ethnicity showed associations between higher CBF and better
      performance on memory and executive functioning/attention in the white European
      group (stbeta = 0.14; p < 0.05 and stbeta = 0.18; p < 0.01 respectively),
      associations were weaker in the South Asian and African Caribbean groups.
      Conclusions: In a multi-ethnic community-based cohort we showed modest
      associations between CBF and cognitive functioning. In particular, we found an
      association between higher CBF and better performance on executive
      functioning/attention and memory in the white European group. The observations
      are consistent with the proposed role of cerebral hemodynamics in cognitive
      decline.

PMID- 30279657
TI  - The Influence of Universal Health Coverage on Life Expectancy at Birth (LEAB) and
      Healthy Life Expectancy (HALE): A Multi-Country Cross-Sectional Study.
AB  - Background: There are substantial differences in long term health outcomes across
      countries, particularly in terms of both life expectancy at birth (LEAB) and
      healthy life expectancy (HALE). Socio-economic status, disease prevention
      approaches, life style and health financing systems all influence long-term
      health goals such as life expectancy. Within this context, universal health
      coverage (UHC) is expected to influence life expectancy as a comprehensive health
      policy. The aim of the study is to investigate this relationship between
      Universal Health Coverage (UHC) and life expectancy. Method: A multi-country
      cross-sectional study was performed drawing on different sources of data (World
      Health Organization, UNDP-Education and World Bank) from 193 UN member countries,
      applying administrative record linkage theory. Descriptive statistics, t-tests,
      Pearson correlations, hierarchical linear regressions were utilized as
      appropriate. Result: Global average healthy life years was shown to be 61.34 +/-
      8.40 and life expectancy at birth was 70.00 +/- 9.3. Standardized coefficients
      from regression analysis found UHC (0.34), child vaccination (Diphtheria
      Pertussis Tetanus-3: 0.17) and sanitation coverage (0.31) were associated with
      significantly increased life expectancy at birth. In contrast, population growth
      was associated with a decrease (0.29). Likewise, unit increases in child
      vaccination (DPT 3), sanitation and UHC would increase healthy life expectancy
      considerably (0.18, 0.31, and 0.40 respectively), whereas the same for population
      growth reduces healthy life expectancy by 0.28. Conclusion: Universal Health
      Coverage (UHC) is a comprehensive health system approach that facilitates a wide
      range of health services and significantly improves the life expectancy at birth
      and healthy life expectancy. This study suggests that specific programs to
      achieve UHC should be considered for countries that have not seen sufficient
      gains in life expectancy as part of the wider push to achieve the Sustainable
      Development Goal (SDG).

PMID- 30279658
TI  - Propensity Score-Based Approaches in High Dimension for Pharmacovigilance Signal
      Detection: an Empirical Comparison on the French Spontaneous Reporting Database.
AB  - Classical methods used for signal detection in pharmacovigilance rely on
      disproportionality analysis of counts aggregating spontaneous reports of a given
      adverse drug reaction. In recent years, alternative methods have been proposed to
      analyze individual spontaneous reports such as penalized multiple logistic
      regression approaches. These approaches address some well-known biases resulting
      from disproportionality methods. However, while penalization accounts for
      computational constraints due to high-dimensional data, it raises the issue of
      determining the regularization parameter and eventually that of an error
      controlling decision rule. We present a new automated signal detection strategy
      for pharmacovigilance systems, based on propensity scores (PS) in high dimension.
      PSs are increasingly used to assess a given association with high-dimensional
      observational healthcare databases in accounting for confusion bias. Our main aim
      was to develop a method having the same advantages as multiple regression
      approaches in dealing with bias, while relying on the statistical multiple
      comparison framework as regards decision thresholds, by considering false
      discovery rate (FDR)-based decision rules. We investigate four PS estimation
      methods in high dimension: a gradient tree boosting (GTB) algorithm from machine
      learning and three variable selection algorithms. For each (drug, adverse event)
      pair, the PS is then applied as adjustment covariate or by using two kinds of
      weighting: inverse proportional treatment weighting and matching weights. The
      different versions of the new approach were compared to a univariate approach,
      which is a disproportionality method, and to two penalized multiple logistic
      regression approaches, directly applied on spontaneous reporting data.
      Performance was assessed through an empirical comparative study conducted on a
      reference signal set in the French national pharmacovigilance database (2000
      2016) that was recently proposed for drug-induced liver injury. Multiple
      regression approaches performed better in detecting true positives and false
      positives. Nonetheless, the performances of the PS-based methods using matching
      weights was very similar to that of multiple regression and better than with the
      univariate approach. In addition to being able to control FDR statistical errors,
      the proposed PS-based strategy is an interesting alternative to multiple
      regression approaches.

PMID- 30279659
TI  - Bystander Effects of Hypoxia-Activated Prodrugs: Agent-Based Modeling Using Three
      Dimensional Cell Cultures.
AB  - Intra-tumor heterogeneity represents a major barrier to anti-cancer therapies.
      One strategy to minimize this limitation relies on bystander effects via
      diffusion of cytotoxins from targeted cells. Hypoxia-activated prodrugs (HAPs)
      have the potential to exploit hypoxia in this way, but robust methods for
      measuring bystander effects are lacking. The objective of this study is to
      develop experimental models (monolayer, multilayer, and multicellular spheroid co
      cultures) comprising 'activator' cells with high expression of prodrug-activating
      reductases and reductase-deficient 'target' cells, and to couple these with agent
      based models (ABMs) that describe diffusion and reaction of prodrugs and their
      active metabolites, and killing probability for each cell. HCT116 cells were
      engineered as activators by overexpressing P450 oxidoreductase (POR) and as
      targets by knockout of POR, with fluorescent protein and antibiotic resistance
      markers to enable their quantitation in co-cultures. We investigated two HAPs
      with very different pharmacology: SN30000 is metabolized to DNA-breaking free
      radicals under hypoxia, while the dinitrobenzamide PR104A generates DNA
      crosslinking nitrogen mustard metabolites. In anoxic spheroid co-cultures,
      increasing the proportion of activator cells decreased killing of both activators
      and targets by SN30000. An ABM parameterized by measuring SN30000 cytotoxicity in
      monolayers and diffusion-reaction in multilayers accurately predicted SN30000
      activity in spheroids, demonstrating the lack of bystander effects and that rapid
      metabolic consumption of SN30000 inhibited prodrug penetration. In contrast,
      killing of targets by PR104A in anoxic spheroids was markedly increased by
      activators, demonstrating that a bystander effect more than compensates any
      penetration limitation. However, the ABM based on the well-studied hydroxylamine
      and amine metabolites of PR104A did not fit the cell survival data, indicating a
      need to reassess its cellular pharmacology. Characterization of extracellular
      metabolites of PR104A in anoxic cultures identified more stable, lipophilic,
      activated dichloro mustards with greater tissue diffusion distances. Including
      these metabolites explicitly in the ABM provided a good description of activator
      and target cell killing by PR104A in spheroids. This study represents the most
      direct demonstration of a hypoxic bystander effect for PR104A to date, and
      demonstrates the power of combining mathematical modeling of
      pharmacokinetics/pharmacodynamics with multicellular culture models to dissect
      bystander effects of targeted drug carriers.

PMID- 30279661
TI  - Dietary Lipids Affect the Onset of Hibernation in the Garden Dormouse (Eliomys
      quercinus): Implications for Cardiac Function.
AB  - Dietary lipids strongly influence patterns of hibernation in heterotherms.
      Increased dietary uptake of n-6 polyunsaturated fatty acids (PUFAs), particularly
      of linoleic acid (LA, C18:2 n-6), enables animals to reach lower body
      temperatures (Tb), lengthens torpor bout duration, and results in lower energy
      expenditure during hibernation. Conversely, dietary n-3 PUFA impacts negatively
      on hibernation performance. PUFA in surrounding phospholipids (PLs) presumably
      modulate the temperature-dependent activity of the sarcoplasmic reticulum (SR)
      Ca2+ ATPase 2 (SERCA2) and thus determine the threshold Tb still allowing proper
      heart function during torpor. We tested the effect of diets enriched with 10% of
      either corn oil ("CO," high n-6 PUFA, e.g., LA) or menhaden oil ["MO," long-chain
      n-3 PUFA, e.g., docosahexaenoic acid (DHA)] on hibernation performance and SERCA2
      activity levels during torpor in garden dormice, an insectivorous, fat-storing
      hibernator. Prior to hibernation, individuals fed the MO diet showed an almost
      nine-times higher DHA levels and 30% lower LA proportions in white adipose tissue
      (WAT), reflecting the fatty acid composition of SR membranes, compared to CO-diet
      fed animals. When fed the MO diet, dormice significantly delayed their mean onset
      of hibernation by almost 4 days (range: 0-12 days), compared with CO-diet fed
      animals. Hibernation onset correlated positively with WAT-DHA levels and
      negatively with WAT-LA proportions prior to hibernation. Subsequently,
      hibernating patterns were similar between the two dietary groups, despite a
      significant difference in WAT-LA but not in WAT-DHA levels in mid-hibernation. SR
      PL fatty acid composition and SERCA2 activity were identical in torpid
      individuals from the two dietary groups in mid-hibernation. In line with our
      previous findings on Syrian hamsters, a granivorous, food-storing hibernator,
      SERCA2 activity correlated positively with LA and negatively with DHA levels of
      SR-PL in torpid dormice, although SERCA2 activity was about three-times higher in
      garden dormice than in Syrian hamsters at similar PL-DHA proportions. Similarly,
      minimal Tb during torpor decreased as SERCA2 activity increased. We conclude
      that: (1) fatty acid composition of SR membranes modulates cardiac SERCA2
      activity, hence determining the minimum Tb tolerated by hibernators, and (2) high
      DHA levels prevent hibernators from entering into torpor, but the critical levels
      differ substantially between species.

PMID- 30279660
TI  - Targeting the Substrate in Ablation of Persistent Atrial Fibrillation: Recent
      Lessons and Future Directions.
AB  - While isolation of the pulmonary veins is firmly established as effective
      treatment for the majority of paroxysmal atrial fibrillation (AF) patients, there
      is recognition that patients with persistent AF have substrate for perpetuation
      of arrhythmia existing outside of the pulmonary veins. Various computational
      approaches have been used to identify targets for effective ablation of
      persistent AF. This paper aims to discuss the clinical aspects of computational
      approaches that aim to identify critical sites for treatment. Various analyses of
      electrogram characteristics have been performed with this aim. Leading techniques
      for electrogram analysis are Complex Fractionated Atrial Electrograms (CFAE) and
      Dominant Frequency (DF). These techniques have been the subject of clinical
      trials of which the results are discussed. Evaluation of the activation patterns
      of atria in AF has been another avenue of research. Focal Impulse and Rotor
      Modulation (FIRM) mapping and forms of Body Surface Mapping aim to characterize
      multiple atrial wavelets, macro-reentry and focal sources which have been
      proposed as basic mechanisms perpetuating AF. Both invasive and non-invasive
      activation mapping techniques are reviewed. The presence of atrial fibrosis
      causes non-uniform anisotropic impulse propagation. Therefore, identification of
      fibrosis by imaging techniques is an avenue of potential research. The leading
      contender for imaging-based techniques is Cardiac Magnetic Resonance (CMR). As
      this technology advances, improvements in resolution and scar identification have
      positioned CMR as the mode of choice for analysis of atrial structure. AF has
      been demonstrated to be associated with obesity, inactivity and diseases of
      modern life. An opportunity exists for detailed computational analysis of the
      impact of risk factor modification on atrial substrate. This ranges from
      microstructural investigation through to examination at a population level via
      registries and public health interventions. Computational analysis of atrial
      substrate has moved from basic science toward clinical application. Future
      directions and potential limitations of such analyses are examined in this
      review.

PMID- 30279662
TI  - Characterization of Vitellogenin and Vitellogenin Receptor of Conopomorpha
      sinensis Bradley and Their Responses to Sublethal Concentrations of Insecticide.
AB  - Conopomorpha sinensis Bradley is the dominant borer pest of Litchi chinesis and
      Euphoria longan. Current management of C. sinensis relies upon insecticide
      application to adult moths. In addition to the direct mortality induced by
      insecticides, a sublethal dose of insecticides also affects growth, survival, and
      reproduction in the exposed insects. Vitellogenin (Vg) and vitellogenin receptor
      (VgR) are normally identified as essential reproduction-related proteins in
      insects. In this study, we characterized these two genes from C. sinensis, and
      investigated their differential responses to sublethal concentrations of
      insecticide. Cloned CsVg and CsVgR consist of 5391 and 5424-bp open reading
      frames, which encode proteins of 1796 and 1807 amino acid residues, respectively.
      The CsVg protein contains the typical vitellogenin, DUF1943 and VWFD domains as
      other reported lepidopteran Vgs. The CsVgR was characterized as a typical low
      density lipoprotein receptor with two highly conserved LBD and EGF precursor
      domains, one hydrophobic transmembrane domain, one cytoplasmic domain, and 13
      putative N-glycosylation sites. We next assessed the sublethal effect of four
      major insecticides on egg-laying in C. sinensis. The toxicity against C. sinensis
      varied among the insecticides tested, with LC50 values ranging from 0.23 ppm for
      chlorpyrifos to 20.00 ppm for beta-cypermethrin, among which emamectin benzoate
      (EB) showed a significant negative impact on egg-laying, survival rate, ovarian
      development, and mating rate of C. sinensis at LC30 doses. Further investigation
      showed that the transcriptional level of CsVg and CsVgR were impaired in
      different way at 24, 48, and 72 h after EB exposure, and this result was in
      agreement with the diminished egg-laying of C. sinensis in the sublethal
      concentration EB-treated group. A repressed transcription level of CsVgR was
      observed at 48 h after treatment, suggesting that EB elicits a delayed response
      in the abundance of CsVgR. These results established different roles of CsVg and
      CsVgR in response to the sublethal effect of insecticides. CsVg might be a better
      parameter than CsVgR for assessing the effect of sublethal insecticides on
      reproduction in C. sinensis.

PMID- 30279664
TI  - Development of a Measure of Postpartum PTSD: The City Birth Trauma Scale.
AB  - Post-traumatic stress disorder (PTSD) affects 4% of women after birth yet there
      are very few questionnaire measures of postpartum PTSD that have been validated
      in this population. In addition, none of the available questionnaires assess
      postpartum PTSD in accordance with criteria specified in the latest edition of
      the Diagnostic and Statistical Manual [DSM-5, (1)]. The City Birth Trauma Scale
      is a 29-item questionnaire developed to measure birth-related PTSD according to
      DSM-5 criteria of: stressor criteria (A), symptoms of re-experiencing (B),
      avoidance (C), negative cognitions and mood (D), and hyperarousal (E), as well as
      duration of symptoms (F), significant distress or impairment (E), and exclusion
      criteria or other causes (H). Two additional items from DSM-IV were also included
      on the basis of evidence suggesting they might be important in this population.
      The first was criterion A2 that women responded to events during birth with
      intense fear, helplessness or horror. The second was symptoms of emotional
      numbing. Items were first reviewed by researchers (n = 9) and postpartum women (n
      = 8) and revised accordingly. The questionnaire was then completed by 950 women
      recruited online. Results showed the City Birth Trauma Scale had excellent
      reliability (Cronbach's alpha = 0.92) and is easy to understand (Flesch reading
      score 64.17). Exploratory factor analysis found two factors which together
      accounted for 56% of the variance: (i) Birth-related symptoms (40.8% variance)
      and (ii) General symptoms (15.5% variance). PTSD symptoms were highly associated
      with distress, impaired functioning, and women reporting they wanted treatment (r
      = 0.50-0.61). Removing DSM-IV A2 criteria only increased births classified as
      traumatic by 2%. Adding the item on emotional numbing did not change the
      psychometric properties of the scale. These items were therefore removed. The
      City Birth Trauma Scale has good psychometric properties and the two symptom
      clusters identified are consistent with previous research on symptoms of
      postpartum PTSD. This scale therefore provides a promising measure of PTSD
      following childbirth that can be used in research and clinical practice. Future
      research should examine the scale's predictive validity using clinical
      interviews.

PMID- 30279663
TI  - Effects of Polarized Training on Cardiometabolic Risk Factors in Young Overweight
      and Obese Women: A Randomized-Controlled Trial.
AB  - Introduction: Volume and intensity are major variables governing exercise
      training-mediated beneficial effects in both athletes and patients. Although
      polarized endurance training optimizes and maximizes physiological gains in
      highly trained individuals, its cardiometabolic protective-effects have not been
      established. The purpose of the present single site, randomized-controlled trial
      was to compare the effects of 12-weeks of high-intensity interval training
      (HIIT), moderate-intensity continuous training (MICT), and polarized volume
      training (POL) programs on cardiometabolic risk factors in young overweight and
      obese women. Materials and Methods: A total of 64 overweight/obese young women
      (age 23.3 +/- 3.8 years, body mass index 33.8 +/- 3.8 kg/m2) were randomly
      assigned to four groups: control group (CTRL), polarized volume training group,
      moderate-intensity endurance training group, and HIIT group. The
      cardiorespiratory capacity, glycemic and lipid profiles, whole-body substrate
      utilization, and body composition were assessed before and after the
      intervention. Results: After the intervention, VO2peak and power output at
      VO2peak increased in all exercised-groups (time effect: p < 0.0001). Power output
      at VT1 was increased only in the POL group compared to the CTRL group (p =
      0.019). Relative fold changes in fasting plasma glucose concentrations decreased
      only in POL group (p = 0.002). Training induced a significant increase in
      relative fat oxidation in all the groups (time effect: p < 0.001). Relative fat
      oxidation increased only in the POL group compared to the CTRL group (training
      effect: p = 0.032). Conclusion: Twelve-weeks of polarized volume training showed
      overall superior effects on cardiorespiratory fitness, basal glycemic control,
      and substrate oxidation in comparison to MICT and HIIT training modalities. These
      data suggest that polarized volume training is an effective non-pharmacological
      treatment strategy for reducing cardiovascular disease risk factors in young
      overweight and obese women. The trial is registered at ISRCTN, number
      ISRCTN34421723.

PMID- 30279665
TI  - Five Interpersonal Factors Are Predictive of the Response to Treatment of Major
      Depression With Antidepressants in Primary Care.
AB  - Introduction: Factors relating to the interpersonal relationship between the
      patient and their physician and social environment are important components,
      which contribute to their response to treatment for major depressive disorder.
      This study aimed to assess the influence of optimism, perfectionism, therapeutic
      alliance, empathy, social support, and adherence to medication regimen in the
      response to antidepressant treatments in the context of normal primary care
      clinical practice. Method: We conducted a prospective study in which 24 primary
      care physicians administered sertraline or escitalopram to 89 patients diagnosed
      with major depressive disorder. The response to treatment and remission of the
      episode was assessed at 4 and 12 weeks by Cox regression. The effect of adherence
      to the medication regimen was assessed by multiple regression statistical
      techniques. Results: Adherence to medication (HR = 0.262, 95% CI = 0.125-0.553, p
      < 0.001) and patient perfectionism (HR = 0.259, 95% CI = 0.017-0.624, p < 0.01)
      negatively predicted the initial response to treatment, whereas patient optimism
      (HR = 1.221, 95% CI = 1.080-1.380, p < 0.05) positively predicted it. Patient
      optimism (HR = 1.247, 95% CI = 1.1-1.4, p < 0.05), empathy perceived by the
      patient (HR = 1.01, 95% CI = 1001-1002, p < 0.05), and therapeutic alliance (HR =
      1.02, 95% CI = 1001-1.04, p < 0.05) positively predicted episode remission, while
      patient perfectionism (HR = 0.219, 95% CI = 0.093-0.515, p < 0.001) and low
      adherence to the treatment regimen (HR = 0.293, 95% CI = 0.145-0.595, p < 0.001)
      negatively predicted it. Finally, social support (p < 0.01) and therapeutic
      alliance (p < 0.05) predicted adherence to the medication regimen. Conclusions:
      In addition to taking the antidepressant drug, other factors including the
      personal interactions between the patient with their primary care physician and
      with their social environment significantly influenced the patients' initial
      response and the final rate of episode remission.

PMID- 30279666
TI  - Methylation of FKBP5 and SLC6A4 in Relation to Treatment Response to Mindfulness
      Based Stress Reduction for Posttraumatic Stress Disorder.
AB  - Mindfulness Based Stress Reduction (MBSR) is an effective non-pharmacologic
      treatment for veterans with PTSD. Extensive work has identified epigenetic
      factors related to PTSD disease risk and pathophysiology, but how these factors
      influence treatment response is unclear. Serotonin signaling and hypothalamic
      pituitary-adrenal (HPA) axis functioning may be perturbed in PTSD and are
      molecular pathways targeted by PTSD treatments. To identify potential biomarkers
      for treatment response, we utilized genomic DNA isolated from peripheral blood
      samples from veterans with PTSD who were responders (n = 11) or non-responders (n
      = 11) to MBSR as part of a clinical trial. We assessed methylation levels at CpG
      sites in regions of the serotonin transporter (SLC6A4) previously associated with
      expression and depression outcomes, as well as the Intron 7 region of the FK506
      binding protein 5 (FKBP5) containing known glucocorticoid response elements
      suggested to regulate this gene. Selected subjects were matched across MBSR
      responder status by baseline symptoms, age, sex, current smoking status, and
      current antidepressant use. Percent methylation was compared between responders
      and non-responders at baseline (pre-MBSR treatment). Additionally, percent change
      in methylation from baseline to post-treatment was compared between responders
      and non-responders. There was a significant time x responder group interaction
      for methylation in FKBP5 intron 7 bin 2 [F (1, 19) = 7.492, p = 0.013] whereby
      responders had a decrease in methylation and non-responders had an increase in
      methylation from before to after treatment in this region. Analyses of the three
      CpG sites within bin 2 revealed a significant time x responder group interaction
      for CpG_35558513 [F (1, 19) = 5.551, p = 0.029] which resides in a known
      glucocorticoid response element (GRE). Decreases in FKBP5 methylation after
      treatment in responders as compared to increases in non-responders suggest that
      effective meditation intervention may be associated with stress-related pathways
      at the molecular level. These preliminary findings suggest that DNA methylation
      signatures within FKBP5 are potential indicators of response to meditation
      treatment in PTSD and require validation in larger cohorts.

PMID- 30279667
TI  - Psychosocial Risk Factors, Burnout and Hardy Personality as Variables Associated
      With Mental Health in Police Officers.
AB  - Among the variables associated with occupational stress, two of the most studied
      are the adverse perceptions of psychosocial risk factors in the workplace and
      burnout. With the rise of positive psychology, other variables of the individual
      type, such as hardy personality have also been the subject of study. No studies
      have been found that jointly examine these variables related to mental health in
      police officers. The aim of this research was to analyze which variables were
      associated with mental health in police officers. A total of 223 policemen (202
      men and 21 women) participated in a cross-sectional study. Of all the variables,
      emotional exhaustion and perception of problems as challenges were the only
      factors introduced in the regression model. These factors must be considered to
      improve both human resource interventions and occupational health practices in
      this professional group.

PMID- 30279668
TI  - The Use of Local and Global Ordering Strategies in Number Line Estimation in
      Early Childhood.
AB  - A lot of research has been devoted to number line estimation in primary school.
      However, less is known about the early onset of number line estimation before
      children enter formal education. We propose that ordering strategies are building
      blocks of number line estimation in early childhood. In a longitudinal study,
      children completed a non-symbolic number line estimation task at age 3.5 and 5
      years. Two ordering strategies were identified based on the children's estimation
      patterns: local and global ordering. Local ordering refers to the correct
      ordering of successive quantities, whereas global ordering refers to the correct
      ordering of all quantities across the number line. Results indicated a
      developmental trend for both strategies. The percentage of children applying
      local and global ordering strategies increased steeply from 3.5 to 5 years of
      age. Moreover, children used more advanced local and global ordering strategies
      at 5 years of age. Importantly, level of strategy use was related to more
      traditional number line estimation outcome measures, such as estimation accuracy
      and regression fit scores. These results provide evidence that children use
      dynamic ordering strategies when solving the number line estimation task in early
      stages of numerical development.

PMID- 30279669
TI  - Cultural Differences in Answerability Judgments.
AB  - Judgments about whether anyone can provide a relevant and correct answer to a
      question are called answerability judgments. Such judgements can be important in
      societal planning and decision making and may vary in different cultural
      contexts. Six hundred participants in each of China, India, and Sweden made
      answerability judgments of six difficult knowledge questions. For each question,
      they choose between three options indicating that they thought the question was
      answerable and a fourth option: "Nobody can answer that question." After each
      question, they rated their confidence that their judgment was correct. Choosing
      "Nobody can answer that question" was significantly more common for the Swedes
      and was uncommon in the Asian samples. The Asian samples showed higher confidence
      in their judgments. We suggest that these differences may be explained by results
      from cross-cultural research, but this study did not investigate specific
      mechanisms. Hence, more research is needed.

PMID- 30279670
TI  - Imagined Intergroup Physical Contact Improves Attitudes Toward Immigrants.
AB  - In this set of research, we investigated the effects of intergroup physical
      contact on intergroup attitudes by relying on indirect contact strategies, namely
      the imagined contact paradigm. We implemented the imagined contact paradigm by
      leading participants to shape the mental imagery upon pictorial information.
      Specifically, in Study 1 participants saw a picture of a white hand touching a
      black hand [i.e., intergroup physical contact condition (InterPC)] or a picture
      of an outdoor scene (i.e., control condition), and were asked to imagine being
      either the toucher or in the outdoor scene, respectively. Results demonstrated
      that InterPC compared to control condition reduced intergroup bias. In Study 2 we
      compared the InterPC condition to a condition in which participants saw a white
      hand touching another white hand [i.e., intragroup physical contact (IntraPC)],
      and imagined to be the toucher. Again, we found that participants in the InterPC
      condition showed reduced intergroup bias compared to the IntraPC. Study 3
      replicated results of Studies 1 and 2 by using an implicit measure of prejudice.
      Also, Study 3 further showed that asking participants to merely look at the
      picture of a white hand touching a black hand, without imagining being the
      toucher was not effective in reducing implicit prejudice. Results were discussed
      with respect to the literature on physical contact and prejudice reduction
      processes.

PMID- 30279671
TI  - Construct Validity and Psychometric Properties of the Hebrew Version of the City
      Birth Trauma Scale.
AB  - As many as third of the women perceive their childbirth as traumatic and although
      prevalence rates vary between studies, around 2-5% of women in community samples
      may develop childbirth-related postpartum post-traumatic stress disorder (PPTSD).
      The City Birth Trauma Scale (BiTS) was developed to address the need for a DSM-5
      based instrument that assesses PPTSD. The BiTS is a self-report questionnaire,
      which covers all DSM-5 PTSD criteria, including the four symptom clusters - re
      experiencing, avoidance, negative mood and cognitions and hyperarousal symptoms.
      The present study aimed to describe the psychometric properties and validate the
      Hebrew version of the BiTS. Five hundred and four mothers of 0- to 12-month-old
      infants were sampled using social media and the snowball method. Respondents
      completed an online survey consisting of a demographic questionnaire and the
      Hebrew versions of the BiTS, the impact of event scale-revised (IES-R), the
      Edinburgh postpartum depression scale (EPDS), and the Pittsburgh Sleep Quality
      Index (PSQI). The Hebrew BiTS demonstrated high internal consistency for the
      total scale (Cronbach alpha = 0.90) and good internal consistency (Cronbach's
      alpha = 0.75-0.85) for the subscales. An exploratory factor (EFA) analysis
      yielded a two-factors solution, accounting for 45% of variance, with general
      symptoms loaded on Factor 1, and childbirth-related symptoms loaded on Factor 2,
      with both factors demonstrating high internal consistency (Cronbach's alpha =
      0.90, 0.85, respectively). High convergent validity for the symptom cluster
      subscales was demonstrated with the parallel IES-R subscales, EPDS and PSQI. A
      two-step cluster analysis indicated that dysphoric and hyperarousal symptoms best
      differentiated the severity of symptoms of respondents across measures. In sum,
      the Hebrew BiTS was psychometrically sound, indicating its utility for clinical
      and non-clinical research. The EFA and cluster analyses support the
      differentiation between symptoms of dysphoria and hyperarousal from trauma (i.e.,
      childbirth) specific symptoms, suggesting that symptoms relating to specific
      aspects of the trauma differ qualitatively from general symptom in the
      phenomenology of PPTSD. Further research using clinical samples and comparing the
      BiTS to DSM-5 diagnosis using clinical interview is needed.

PMID- 30279672
TI  - The Role of Approximate Number System in Different Mathematics Skills Across
      Grades.
AB  - Although approximate number system (ANS) has been found to predict mathematics
      ability, it remains unclear if both aspects of ANS (symbolic and non-symbolic
      estimation) contribute equally well to mathematics performance and if their
      contribution varies as a function of the mathematics outcome and grade level.
      Thus, in this study, we examined the effects of both aspects of ANS on different
      mathematics skills across three grade levels. Three hundred eleven children (100
      children from kindergarten, 107 children from Grade 2, and 104 children from
      Grade 4) from two kindergartens and three elementary schools in Shanghai, China,
      were assessed on measures of ANS (dot estimation and number line estimation),
      general cognitive ability (nonverbal intelligence, inhibition, and working
      memory), and mathematics abilities (numerical operations and mathematical problem
      solving in all grades, early mathematical skills in kindergarten, and calculation
      fluency in Grades 2 and 4). Results of hierarchical regression analyses showed
      that, in kindergarten, non-symbolic estimation predicted all mathematics skills
      even after controlling for age, gender, and general cognitive ability. In Grades
      2 and 4, symbolic estimation accounted for unique variance in mathematical
      problem solving, but not in calculation fluency. Symbolic estimation also
      predicted numerical operations in Grade 4. Taken together, these findings suggest
      that in the early phases of mathematics development different aspects of ANS
      contribute to different mathematics skills.

PMID- 30279673
TI  - How Eye Movements Stabilize Posture in Patients With Bilateral Vestibular
      Hypofunction.
AB  - Chronic patients with bilateral vestibular hypofunction (BVH) complain of
      oscillopsia and great instability particularly when vision is excluded and on
      irregular surfaces. The real nature of the visual input substituting to the
      missing vestibular afferents and improving posture control remains however under
      debate. Is retinal slip involved? Do eye movements play a substantial role? The
      present study tends to answer this question in BVH patients by investigating
      their posture stability during quiet standing in four different visual
      conditions: total darkness, fixation of a stable space-fixed target, and pursuit
      of a visual target under goggles delivering visual input rate at flicker
      frequency inducing either slow eye movements (4.5 Hz) or saccades (1.2 Hz).
      Twenty one chronic BVH patients attested by both the caloric and head impulse
      test were examined by means of static posturography, and compared to a control
      group made of 21 sex-and age-matched healthy participants. The posturography data
      were analyzed using non-linear computation of the center of foot pressure (CoP)
      by means of the wavelet transform (Power Spectral Density in the visual frequency
      part, Postural Instability Index) and the fractional Brownian-motion analysis
      (stabilogram-diffusion analysis, Hausdorff fractal dimension). Results showed
      that posture stability was significantly deteriorated in darkness in the BVH
      patients compared to the healthy controls. Strong improvement of BVH patients'
      posture stability was observed during fixation of a visual target, pursuit with
      slow eye movements, and saccades, whereas the postural performance of the control
      group was less affected by the different visual conditions. It is concluded that
      BVH patients improve their posture stability by (1) using extraocular signals
      from eye movements (efference copy, muscle re-afferences) much more than the
      healthy participants, and (2) shifting more systematically than the controls to a
      more automatic mode of posture control when they are in dual-task conditions
      associating the postural task and a concomitant visuo- motor task.

PMID- 30279674
TI  - Degraded Synergistic Recruitment of sEMG Oscillations for Cerebral Palsy Infants
      Crawling.
AB  - Background: Synergistic recruitment of muscular activities is a generally
      accepted mechanism for motor function control, and motor dysfunction, such as
      cerebral palsy (CP), destroyed the synergistic electromyography activities of
      muscle group for limb movement. However, very little is known how motor
      dysfunction of CP affects the organization of the myoelectric frequency
      components due to the abnormal motor unit recruiting patterns. Objectives:
      Exploring whether the myoelectric activity can be represented with synergistic
      recruitment of surface electromyography (sEMG) frequency components; evaluating
      the effect of CP motor dysfunction on the synergistic recruitment of sEMG
      oscillations. Methods: Twelve CP infants and 17 typically developed (TD) infants
      are recruited for self-paced crawling on hands and knees. sEMG signals have been
      recorded from bilateral biceps brachii (BB) and triceps brachii (TB) muscles.
      Multi-scale oscillations are extracted via multivariate empirical mode
      decomposition (MEMD), and non-negative matrix factorization (NMF) method is
      employed to obtain synergistic pattern of these sEMG oscillations. The
      coefficient curve of sEMG oscillation synergies are adopted to quantify the time
      varying recruitment of BB and TB myoelectric activity during infants crawling.
      Results: Three patterns of sEMG oscillation synergies with specific frequency
      ranges are extracted in BB and TB of CP or TD infants. The contribution of low
      frequency oscillation synergy of BB in CP group is significantly less than that
      in TD group (p < 0.05) during forward swing phase for slow contraction; however,
      this low-frequency oscillation synergy keep higher level during the backward
      swing phase crawling. For the myoelectric activities of TB, there is not enough
      high-frequency oscillation recruitment of sEMG for the fast contraction in
      propulsive phase of CP infants crawling. Conclusion: Our results reveal that, the
      myoelectric activities of a muscle can be manifested as sEMG oscillation
      synergies, and motor dysfunction of CP degrade the synergistic recruitment of
      sEMG oscillations due to the impaired CNS regulation and destroyed MU/muscle
      fiber. Our preliminary work suggests that time-varying coefficient curve of sEMG
      oscillation synergies is a potential index to evaluate the abnormal recruitment
      of electromyography activities affected by CP disorders.

PMID- 30279676
TI  - Concussions in Sledding Sports and the Unrecognized "Sled Head": A Systematic
      Review.
AB  - Background: Sport-related concussion is a significant public health concern.
      Little research has been conducted on sport-related concussion and injury
      prevention strategies in competitive sledding sports like bobsleigh, luge, and
      skeleton. Athletes have identified "sled head" as a key concern due to its
      symptom burden. Purpose: To summarize our knowledge of the prevalence of
      concussion and related symptoms in sledding sports; to utilize Haddon's Matrix to
      inform and define strategies for injury prevention. Methods: An independent
      information specialist conducted a search for the known literature on injuries in
      non-recreational sledding sports, and specifically for concussion via OVID
      Medline, CINAHL, the Cochrane Database, EMBASE, PsycInfo, PubMed, Scopus, and the
      Web of Sciences from 1946 to December 2017. After iterative searches of reference
      sections, a total of 844 articles were assessed for inclusion. Results: Nine
      articles were included for review. Concussions are a common occurrence in elite
      sledding sport athletes, affecting 13-18% of all sledding athletes. Significant
      variance exists between events, indicating a potential effect of the ice track in
      injury risk. The condition known as "sled head" is discussed and identified as a
      key point of further investigation. A number of potential injury prevention
      strategies are discussed. Interpretation: Head injuries and concussions are an
      important injury for elite sledding sports and a number of avenues exist for
      prevention. More work is required to delineate the mechanisms, characteristics,
      natural history and management of "sled head."

PMID- 30279675
TI  - Structural, Microstructural, and Metabolic Alterations in Primary Progressive
      Aphasia Variants.
AB  - Neuroimaging studies have described the brain alterations in primary progressive
      aphasia (PPA) variants (semantic, logopenic, nonfluent/agrammatic). However, few
      studies combined T1, FDG-PET, and diffusion MRI techniques to study atrophy,
      hypometabolism, and tract alterations across the three PPA main variants. We
      therefore explored a large early-stage cohort of semantic, logopenic and
      nonfluent/agrammatic variants (N = 86) and of 23 matched healthy controls with
      anatomical MRI (cortical thickness), FDG PET (metabolism) and diffusion MRI
      (white matter tracts analyses), aiming at identifying cortical and sub-cortical
      brain alterations, and confronting these alterations across imaging modalities
      and aphasia variants. In the semantic variant, there was cortical thinning and
      hypometabolism in anterior temporal cortices, with left-hemisphere predominance,
      extending toward posterior temporal regions, and affecting tracts projecting to
      the anterior temporal lobes (inferior longitudinal fasciculus, uncinate
      fasciculus) and tracts projecting to or running nearby posterior temporal
      cortices: (superior longitudinal fasciculus, inferior frontal-occipital
      fasciculus). In the logopenic variant metabolic alterations were more extensive
      than atrophy affecting mainly the left temporal-parietal junction and extending
      toward more anterior temporal cortices. Metabolic and tract data were coherent
      given the alterations of the left superior and inferior longitudinal fasciculus
      and the left inferior frontal-occipital fasciculus. In the nonfluent/agrammatic
      variant cortical thinning and hypometabolism were located in the left frontal
      cortex but Broca's area was only affected on metabolic measures. Metabolic and
      tract alterations were coherent as reflected by damage to the left uncinate
      fasciculus connecting with Broca's area. Our findings provide a full-blown
      statistically robust picture of brain alterations in early-stage variants of
      primary progressive aphasia which has implications for diagnosis, classification
      and future therapeutic strategies. They demonstrate that in logopenic and
      semantic variants patterns of brain damage display a non-negligible overlap in
      temporal regions whereas they are substantially distinct in the
      nonfluent/agrammatic variant (frontal regions). These results also indicate that
      frontal networks (combinatorial syntax/phonology) and temporal networks
      (lexical/semantic representations) constitute distinct anatomo-functional
      entities with differential vulnerability to degenerative processes in aphasia
      variants. Finally, the identification of the specific damage patterns could open
      an avenue for trans-cranial stimulation approaches by indicating the appropriate
      target-entry into the damaged language system.

PMID- 30279678
TI  - Socioeconomic Position and Picky Eating Behavior Predict Disparate Weight
      Trajectories in Infancy.
AB  - Infant weight gain has long-term implications for the establishment of overall
      health. We examined whether socioeconomic position (SEP), the use of pressure as
      a feeding practice, and picky eating relate to changes infant in weight-for
      length (WFL). A modified developmental design was used to examine whether current
      levels of child picky eating, parental use of pressure, and SEP were associated
      with changes in WFL during infancy. Health providers distributed survey packets
      during routine well-child visits made in the homes of families with young
      children in New Zealand (n = 193). Primary caregivers of young children provided
      their child's current level of picky eating, their use of pressure, and their
      SEP. They also reported their child's professionally-measured WFL from birth, 8,
      15, and 21 months of age. A multi-level modeling analysis yielded an interaction
      between SEP and picky eating in predicting infant weight change over time.
      Children who had a low SEP and were not picky eaters were on the highest WFL
      trajectory and children who had a low SEP and were picky eaters were lowest on
      the WFL trajectory. A main effect revealed that higher levels of parental
      pressure predicted lower WFL in infants at each age, but did not interact with
      SEP or picky eating. Findings from this study indicate that the combination of
      eating behavior and SEP are associated with differential infant growth patterns.
      These results suggest that eating behavior and SEP should be included in the
      development of interventions designed to achieve healthy weight during childhood.

PMID- 30279677
TI  - Progestin and Nuclear Progestin Receptor Are Essential for Upregulation of
      Metalloproteinase in Zebrafish Preovulatory Follicles.
AB  - Ovulation requires proteinases to promote the rupture of ovarian follicles.
      However, the identity of these proteinases remains unclear. In our previous
      studies using RNA-seq analysis of differential expressed genes, we found
      significant down-regulation of five metalloproteinases: adam8b (a disintegrin and
      metalloproteinase domain 8b), adamts8a (a disintegrin and metalloproteinase with
      thrombospondin motif 8a), adamts9, mmp2 (matrix metalloproteinase 2), and mmp9 in
      the nuclear progestin receptor knockout (pgr -/-) zebrafish that have failed to
      ovulate. We hypothesize that these metalloproteinases are responsible for
      ovulation and are regulated by progestin and Pgr. In this study, we first
      determined the expression of these five metalloproteinases and adamts1 in
      preovulatory follicles at different times within the spawning cycle in pgr -/-
      and wildtype (wt) zebrafish and under varying hormonal treatments. We found that
      transcripts of adam8b, adamts1, adamts9, and mmp9 increased drastically in the
      preovulatory follicular cells of wt female zebrafish, while changes of adamts8a
      and mmp2 were not significant. This increase of adam8b, adamts9, and mmp9 was
      significantly reduced in pgr -/-, whereas expression of adamts1 was not affected
      in pgr -/- zebrafish. Among upregulated metalloproteinases, adamts9 mRNA was
      found to be expressed specifically in follicular cells. Strong immunostaining of
      Adamts9 protein was observed in the follicular cells of wt fish, and this
      expression was reduced drastically in pgr -/-. Interestingly, about an hour prior
      to the increase of metalloproteinases in wt fish, both Pgr transcript and protein
      increased transiently in preovulatory follicular cells. The results from in vitro
      experiments showed that adamts9 expression markedly increased in a dose, time and
      Pgr-dependent manner when preovulatory follicles were exposed to a progestin,
      17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP). Taken together, our results
      provide the first evidence that upregulation of adamts9 occurs specifically in
      preovulatory follicular cells of zebrafish prior to ovulation. Progestin and its
      receptor (Pgr) are essential for the upregulation of metalloproteinases.

PMID- 30279679
TI  - The New TNM Staging System for Thyroid Cancer and the Risk of Disease
      Downstaging.
AB  - In October 2016 the American Joint Committee on Cancer (AJCC) published the 8th
      edition of the AJCC/TNM cancer staging system and it has been introduced in
      clinical practice since 1st January 2018. The effect of most of the changes in
      the new edition was the downstaging of a significant number of patients into
      lower stages, reflecting their low risk of thyroid cancer-related death. One of
      the most relevant modification refers to the role of the microscopic extra
      thyroidal tumor invasion, which is no longer considered as criterion for the
      classification of T3 tumors. With the present study we want to assess the impact
      of the changes of the new staging system and therefore we analyzed or casistic of
      84 T1-T3 thyroid-cancer patients. The results of our analysis show that he
      downstaging of patients according to the 8th TNM edition does not necessarily
      reflect less aggressive disease: we actually reported 2 lymph-nodal recurrences
      (40%) in the five patients that were downstaged from pT3 to pT2 and the lypmh
      nodal recurrence rate for stage I rises from 0% with the 7th TNM edition to 5.3%
      with the 8th edition.

PMID- 30279680
TI  - Expanding the Current Knowledge About the Role of Interleukin-10 to Major
      Concerning Bacteria.
AB  - Interleukin-10 (IL-10) is one of the most important anti-inflammatory cytokine
      produced during bacterial infection. Two related phenomena explain the importance
      of IL-10 production in this context: first, the wide range of cells able to
      produce this cytokine and second, the wide effects that it causes on target
      cells. In a previous report we described opposing roles of IL-10 production
      during bacterial infection. Overall, during infections caused by intracellular
      bacteria or by pathogens that modulate the inflammatory response, IL-10
      production facilitates bacterial persistence and dissemination within the host.
      Whereas during infections caused by extracellular or highly inflammatory
      bacteria, IL-10 production reduces host tissue damage and facilitates host
      survival. Given that these data were obtained using antibiotic susceptible
      bacteria, the potential application of these studies to multi-drug resistant
      (MDR) bacteria needs to be evaluated. MDR bacteria can become by 2050 a major
      death cause worldwide, not only for its ability to resist antimicrobial therapy
      but also because the virulence of these strains is different as compared to
      antibiotic susceptible strains. Therefore, it is important to understand the
      interaction of MDR-bacteria with the immune system during infection. This review
      discusses the current data about the role of IL-10 during infections caused by
      major circulating antibiotic resistant bacteria. We conclude that the production
      of IL-10 improves host survival during infections caused by extracellular or
      highly inflammatory bacteria, however, it is detrimental during infections caused
      by intracellular bacteria or bacterial pathogens that modulate the inflammatory
      response. Importantly, during MDR-bacterial infections a differential IL-10
      production has been described, compared to non-MDR bacteria, which might be due
      to virulence factors specific of MDR bacteria that modulate production of IL-10.
      This knowledge is important for the development of new therapies against
      infections caused by these bacteria, where antibiotics effectiveness is
      dramatically decreasing.

PMID- 30279682
TI  - Switching and Torque Generation in Swarming E. coli.
AB  - Escherichia coli swarm on semi-solid surfaces with the aid of flagella. It has
      been hypothesized that swarmer cells overcome the increased viscous drag near
      surfaces by developing higher flagellar thrust and by promoting surface wetness
      with the aid of a flagellar switch. The switch enables reversals between
      clockwise (CW) and counterclockwise (CCW) directions of rotation of the flagellar
      motor. Here, we measured the behavior of flagellar motors in swarmer cells.
      Results indicated that although the torque was similar to that in planktonic
      cells, the tendency to rotate CCW was higher in swarmer cells. This suggested
      that swarmers likely have a smaller pool of phosphorylated CheY. Results further
      indicated that the upregulation of the flagellin gene was not critical for
      flagellar thrust or swarming. Consistent with earlier reports, moisture added to
      the swarm surface restored swarming in a CCW-only mutant, but not in a FliG
      mutant that rotated motors CW-only (FliGCW). Fluorescence assays revealed that
      FliGCW cells grown on agar surfaces carried fewer flagella than planktonic FliGCW
      cells. The surface-dependent reduction in flagella correlated with a reduction in
      the number of putative flagellar preassemblies. These results hint toward a
      possibility that the conformational dynamics of switch proteins play a role in
      the proper assembly of flagellar complexes and flagellar export, thereby aiding
      bacterial swarming.

PMID- 30279681
TI  - Microbial Communities Associated With Indigo Fermentation That Thrive in
      Anaerobic Alkaline Environments.
AB  - Indigo fermentation, which depends on the indigo-reducing action of
      microorganisms, has traditionally been performed to dye textiles blue in Asia as
      well as in Europe. This fermentation process is carried out by naturally
      occurring microbial communities and occurs under alkaline, anaerobic conditions.
      Therefore, there is uncertainty regarding the fermentation process, and many
      unknown microorganisms thrive in this unique fermentation environment. Until
      recently, there was limited information available on bacteria associated with
      this fermentation process. Indigo reduction normally occurs from 4 days to 2
      weeks after initiation of fermentation. However, the changes in the microbiota
      that occur during the transition to an indigo-reducing state have not been
      elucidated. Here, the structural changes in the bacterial community were
      estimated by PCR-based methods. On the second day of fermentation, a large change
      in the redox potential occurred. On the fourth day, distinct substitution of the
      genus Halomonas with the aerotolerant genus Amphibacillus was observed,
      corresponding to marked changes in indigo reduction. Under open-air conditions,
      indigo reduction during the fermentation process continued for 6 months on
      average. The microbiota, including indigo-reducing bacteria, was continuously
      replaced with other microbial communities that consisted of other types of indigo
      reducing bacteria. A stable state consisting mainly of the genus Anaerobacillus
      was also observed in a long-term fermentation sample. The stability of the
      microbiota, proportion of indigo-reducing microorganisms, and appropriate
      diversity and microbiota within the fluid may play key factors in the maintenance
      of a reducing state during long-term indigo fermentation. Although more than 10
      species of indigo-reducing bacteria were identified, the reduction mechanism of
      indigo particle is riddle. It can be predicted that the mechanism involves
      electrons, as byproducts of metabolism, being discarded by analogs mechanisms
      reported in bacterial extracellular solid Fe3+ reduction under alkaline anaerobic
      condition.

PMID- 30279684
TI  - A Major Facilitator Superfamily Transporter Regulated by the Stress-Responsive
      Transcription Factor Yap1 Is Required for Resistance to Fungicides, Xenobiotics,
      and Oxidants and Full Virulence in Alternaria alternata.
AB  - Alternaria alternata relies on the ability to produce a host-selective toxin and
      to detoxify reactive oxygen species to successfully colonize the host. An A.
      alternata major facilitator superfamily transporter designated AaMFS54 was
      functionally characterized by analysis of loss- and gain-of-function mutations to
      better understand the factors required for fungal pathogenesis. AaMFS54 was
      originally identified from a wild-type expression library after being subtracted
      with that of a mutant impaired for the oxidative stress-responsive transcription
      regulator Yap1. AaMFS54 contains 14 transmembrane helixes. Fungal mutant lacking
      AaMFS54 produced fewer conidia and increased sensitivity to many potent oxidants
      (potassium superoxide and singlet-oxygen generating compounds), xenobiotics
      (2,3,5-triiodobenzoic acid and 2-chloro-5-hydroxypyridine), and fungicides
      (clotrimazole, fludioxonil, vinclozolin, and iprodione). AaMFS54 mutant induced
      necrotic lesion sizes similar to those induced by wild-type on leaves of
      susceptible citrus cultivars after point inoculation with spore suspensions.
      However, the mutant produced smaller colonies and less fluffy hyphae on the
      affected leaves. Virulence assays on citrus leaves inoculated by spraying with
      spores revealed that AaMFS54 mutant induced less severe lesions than wild-type,
      indicating the requirement of AaMFS54 in pathogenesis. All defective phenotypes
      were restored in a strain re-acquiring a functional copy of AaMFS54. Northern
      blotting analysis revealed that the expression of AaMFS54 was suppressed by
      xenobiotics. The current studies indicate that the Yap1-mediated transporter
      plays a role in resistance to toxic oxidants and fungicides in A. alternata. The
      relationships of MFS transporters with other regulatory components conferring
      stress resistance and A. alternata pathogenesis are also discussed.

PMID- 30279683
TI  - Dietary Bile Salt Types Influence the Composition of Biliary Bile Acids and Gut
      Microbiota in Grass Carp.
AB  - Lipid metabolism can influence host's health. There is increasing evidence for
      interplay between two key regulating factors in lipid metabolism: bile acids
      (BAs) and gut microbiota. However, very little is known about how types of
      different diet-supplemented bile salts (BS) influence this interaction in vivo.
      We sought to explore these relationships using grass carp (Ctenopharyngodon
      idellus), which often suffers functional disorder of liver and gallbladder. We
      studied fluctuations of BAs in the gall and changes of microbial communities in
      the gut in response to seven different diets: five different BS, chelating BS
      agent, and control. The BS comprised two primary BS [sodium taurochololate (TCAS)
      and sodium taurochenodeoxycholate (TCDCAS)], sodium tauroursodeoxycholate
      (TUDCAS), and two secondary BS [sodium taurodeoxycholate (TDCAS) and sodium
      taurolithocholate (TLCAS)]. Supplementation of primary BS caused a more
      significant fluctuation of biliary BAs than secondary BS, and TCAS caused a more
      prominent increase than TCDCAS and TUDCAS. For the gut microbiota, primary BS
      tended to increase their diversity and induce community succession, secondary BS
      resulted in a higher firmicutes/bacteroidetes ratio, while TUDCAS had no
      significant effects. Changes of the gut microbiota triggered by different types
      of BS caused alteration in BAs biotransformation. Two-obesity-associated
      families, Lachnospiraceae and Ruminococcaceae were positively correlated with
      biliary cholic acid (CA), taurochenodeoxycholic acid (TCDCA), and deoxycholic
      acid (DCA). As both primary and secondary BS resulted in increased synthesis of
      toxic secondary Bas by the gut microbiota, future studies should pay closer
      attention to gut microbiota when considering BA treatment.

PMID- 30279685
TI  - Low-Dose Radiotherapy Ameliorates Advanced Arthritis in hTNF-alpha tg Mice by
      Particularly Positively Impacting on Bone Metabolism.
AB  - Inflammation and bone erosion are central in rheumatoid arthritis (RA). Even
      though effective medications for control and treatment of RA are available,
      remission is only seen in a subset of patients. Treatment with low-dose
      radiotherapy (LD-RT) which has been already successfully used for amelioration of
      symptoms in benign diseases should be a promising approach to reduce pain,
      inflammation, and particularly bone erosion in patients with RA. Even though anti
      inflammatory effects of LD-RT are already described with non-linear dose response
      relationships, and pain-reducing effects have been clinically observed, the
      underlying mechanisms are widely unknown. Besides immune cells many other cell
      types, such as fibroblast-like synoviocytes (FLS), osteoclasts, and osteoblast
      are present in the affected joint and might be modulated by LD-RT. For this
      study, these cell types were obtained from human tumor necrosis factor-alpha
      transgenic (hTNF-alpha tg) mice and were consecutively exposed to different doses
      of ionizing radiation (0.1, 0.5, 1.0, and 2.0 Gy, respectively) in vitro. In
      order to study the in vivo effects of LD-RT within the arthritic joint, hind paws
      of arthritic hTNF-alpha tg mice were locally irradiated with 0.5 Gy, a single
      dose per fraction that is known for good clinical responses. Starting at a dose
      of 0.5 Gy, proliferation of FLS was reduced and apoptosis significantly enhanced
      with no changes in necrosis. Further, expression of RANK-L was slightly reduced
      following irradiation with particularly 0.5 Gy. Starting from 0.5 Gy, the numbers
      of differentiated osteoclasts were significantly reduced, and a lower bone
      resorbing activity of treated osteoclasts was also observed, as monitored via pit
      formation and Cross Laps presence. LD-RT had further a positive effect on
      osteoblast-induced mineralization in a discontinuous dose response relationship
      with 0.5 Gy being most efficient. An increase of the gene expression ratio of
      OPG/RANK-L at 0.1 and 0.5 Gy and of production of OPG at 0.5 and 1.0 Gy was
      observed. In vivo, LD-RT resulted in less severe arthritis in arthritic hTNF
      alpha tg mice and in significant reduction of inflammatory and erosive area with
      reduced osteoclasts and neutrophils. Locally applied LD-RT can, therefore, induce
      a beneficial micro-environment within arthritic joints by predominantly
      positively impacting on bone metabolism.

PMID- 30279687
TI  - FIBCD1 Binds Aspergillus fumigatus and Regulates Lung Epithelial Response to Cell
      Wall Components.
AB  - Aspergillus fumigatus (A. fumigatus) is a ubiquitous fungus of clinical
      importance associated with development of various pulmonary diseases and allergic
      hypersensitivity reactions. It is protected against environmental stress by a
      cell wall that contains polysaccharides such as chitin. We previously
      demonstrated that fibrinogen C domain-containing protein 1 (FIBCD1) is a membrane
      bound protein that binds chitin through a conserved S1 binding site and is
      expressed in intestinal epithelium and salivary glands. Here, we further
      localized FIBCD1 protein expression at the surface of bronchial and alveolar
      human lung epithelium, observed recognition of A. fumigatus cell wall with S1
      site-independent recognition. We observed FIBCD1-mediated suppression of IL-8
      secretion, mucin production, and transcription of genes associated with airway
      inflammation and homeostasis in FIBCD1-transfected lung epithelial cells. These
      modulations were generally enforced by stimulation with A. fumigatus cell wall
      polysaccharides. In parallel, we demonstrated a FIBCD1-mediated modulation of IL
      8 secretion induced by TLR2,-4, and -5. Collectively, our findings support FIBCD1
      as a human lung epithelial pattern recognition receptor that recognizes the
      complex A. fumigatus cell wall polysaccharides and modulates the lung epithelial
      inflammatory response by suppressing inflammatory mediators and mucins.

PMID- 30279686
TI  - Anti-LL37 Antibodies Are Present in Psoriatic Arthritis (PsA) Patients: New
      Biomarkers in PsA.
AB  - Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with
      psoriasis. A third of psoriatic patients develop PsA via unknown mechanisms. No
      reliable diagnostic markers are available for PsA, or prognostic biomarkers for
      PsA development in psoriasis. We previously uncovered a pro-inflammatory role for
      cathelicidin LL37 in lesional psoriasis skin. LL37 binds nucleic acids and
      stimulates plasmacytoid/myeloid dendritic cells (pDC, mDCs) to secrete type I
      interferon (IFN-I) and pro-inflammatory factors. LL37 becomes an autoantigen for
      psoriatic Th1-Th17/CD8 T cells. Anti-LL37 antibodies were detected in systemic
      lupus erythematosus, an autoimmune disease characterized by neutrophil
      extracellular-traps release (NETosis) in target organs. LL37 can be substrate of
      irreversible post-translational modifications, citrullination or carbamylation,
      linked to neutrophil activity. Here we analyzed inflammatory factors, included
      LL37, in PsA and psoriasis plasma and PsA synovial fluids (SF)/biopsies. We show
      that LL37 (as a product of infiltrating neutrophils) and autoantibodies to LL37
      are elevated in PsA, but not OA SF. Anti-LL37 antibodies correlate with clinical
      inflammatory markers. Anti-carbamylated/citrullinated-LL37 antibodies are present
      in PsA SF/plasma and, at lower extent, in psoriasis plasma, but not in controls.
      Plasma anti-carbamylated-LL37 antibodies correlate with PsA (DAS44) but not
      psoriasis (PASI) disease activity. Ectopic lymphoid structures, and deposition of
      immunoglobulin-(Ig)G-complexes (IC) co-localizing with infiltrating neutrophils,
      are observed in PsA and not OA synovial tissues (ST). Activated complement (C5a,
      C9), GM-CSF and IFN-I are up-regulated in PsA and not OA synovia and in PsA and
      psoriasis plasma but not in HD. C9 and GM-CSF levels in PsA SF correlate with
      clinical inflammatory markers and DAS44 (C9) and with anti
      carbamylated/citrullinated-LL37 antibodies (GM-CSF and IFN-I). Thus, we uncover a
      role for LL37 as a novel PsA autoantibody target and correlation studies suggest
      participation of anti-LL37 antibodies to PsA pathogenesis. Notably, plasma
      antibodies to carbamylated-LL37, which correlate with DAS44, suggest their use as
      new disease activity markers. GM-CSF and complement C5a and C9 elevation may be
      responsible for autoantigens release by neutrophils and their modification,
      fueling inflammation and autoreactivity establishment. Finally, targeting GM-CSF,
      C5a, C9 can be beneficial in PsA.

PMID- 30279689
TI  - Treatment of Granulomas in Patients With Ataxia Telangiectasia.
AB  - Background: Ataxia telangiectasia (A-T) is a devastating multi-system disorder
      characterized by progressive cerebellar ataxia, growth retardation,
      immunodeficiency, chronic pulmonary disease and chromosomal instability.
      Cutaneous granulomas are a known phenomenon in A-T but extra-dermal manifestation
      of granulomas at bone and synovia has not been reported so far. The clinical
      presentation, immunological findings, the long-term course and treatment options
      of eight patients with severe granulomas will be reported. Methods: From our
      cohort of 44 classical A-T patients, eight patients aged 2-11 years (18.2%)
      presented with granulomas. Immunological features of patients with and without
      granulomas were compared. Five patients suffered from cutaneous manifestation, in
      two patients we detected a bone and in one a joint involvement. Patients with
      significant extra-dermal involvement as well as one patient with massive skin
      manifestation were treated with TNF inhibitors. The patient with granulomas at
      his finger joint and elbow was treated with hematopoietic stem cell
      transplantation (HSCT). Results: Interestingly, seven of eight patients with
      granulomas were total IgA deficient, but there were no differences in IgG and IgM
      levels. All lymphocytes subsets were equally distributed except patients with
      granuloma had significantly lower naive CD8 cells. In patients without treatment,
      four of eight showed a slow but significant enlargement of the granuloma.
      Treatment success with TNF inhibitors was variable. In one patient, treatment
      with TNF inhibitors led to a total remission for 3 years up to now. In two
      patients, treatment with TNF inhibitors led to a partial regression of
      granulomas. Treatment interruptions caused deterioration again. Conclusions:
      Granulomas in A-T progress slowly over years and can lead to significant
      morbidity.Treatment with TNF inhibitors was safe and in part successful in our
      patients. Interestingly HSCT leads to complete remission, and indicates that
      aberrant immune function is responsible for granulomas in A-T patients. What This
      Study Adds to the Field: Granulomas in A-T progress slowly over years and can
      lead to significant morbidity. Treatment with TNF inhibitors was safe and in part
      successful in our patients. AT A GLANCE COMMENTARY: Scientific knowledge on the
      subject: Little is known about the clinical presentation, course and treatment of
      granulomas in ataxia telangiectasia (A-T). In addition, this is the first report
      of extra-dermal manifestation of granulomas at bone and synovia in patients with
      A-T. What This Study Adds to the Field: Granulomas in A-T progress slowly over
      years and can lead to significant morbidity. Treatment with TNF inhibitors was
      safe and in part successful in our patients.

PMID- 30279688
TI  - Taurodeoxycholate Increases the Number of Myeloid-Derived Suppressor Cells That
      Ameliorate Sepsis in Mice.
AB  - Bile acids (BAs) control metabolism and inflammation by interacting with several
      receptors. Here, we report that intravenous infusion of taurodeoxycholate (TDCA)
      decreases serum pro-inflammatory cytokines, normalizes hypotension, protects
      against renal injury, and prolongs mouse survival during sepsis. TDCA increases
      the number of granulocytic myeloid-derived suppressor cells (MDSCLT) distinctive
      from MDSCs obtained without TDCA treatment (MDSCL) in the spleen of septic mice.
      FACS-sorted MDSCLT cells suppress T-cell proliferation and confer protection
      against sepsis when adoptively transferred better than MDSCL. Proteogenomic
      analysis indicated that TDCA controls chromatin silencing, alternative splicing,
      and translation of the immune proteome of MDSCLT, which increases the expression
      of anti-inflammatory molecules such as oncostatin, lactoferrin and CD244. TDCA
      also decreases the expression of pro-inflammatory molecules such as neutrophil
      elastase. These findings suggest that TDCA globally edits the proteome to
      increase the number of MDSCLT cells and affect their immune-regulatory functions
      to resolve systemic inflammation during sepsis.

PMID- 30279690
TI  - Physiological Stimuli Induce PAD4-Dependent, ROS-Independent NETosis, With Early
      and Late Events Controlled by Discrete Signaling Pathways.
AB  - Neutrophils are known to extrude decondensed chromatin, thus forming NETs
      (neutrophil extracellular traps). These structures immobilize pathogens, thereby
      preventing their spreading, and are also adorned with antimicrobial molecules.
      NETs can also influence pathogenesis in chronic inflammation, autoimmunity, and
      cancer. Despite the importance of NETs, the molecular mechanisms underlying their
      formation, as well as the upstream signaling pathways involved, are only
      partially understood. Likewise, current methodological approaches to quantify
      NETs suffer from significant drawbacks, not the least being the inclusion of a
      significant non-specific signal. In this study, we used novel, fluorescent
      polymers that only bind extruded chromatin, allowing a specific and standardized
      quantification of NETosis. This allowed us to reliably rank the relative potency
      of various physiologic NET inducers. In neutrophils activated with such stimuli,
      inhibition of the Syk or PI3K pathways blocked NETosis by acting upon late events
      in NET formation. Inhibition of the TAK1, p38 MAPK, or MEK pathways also hindered
      NETosis, but by acting on early events. By contrast, inhibiting PKC, Src family
      kinases, or JNK failed to prevent NETosis; cycloheximide or actinomycin D were
      also ineffective. Expectedly, NET formation was deeply compromised following
      inhibition of the NADPH oxidase in PMA-activated neutrophils, but was found to be
      ROS-independent in response to physiological agonists. Conversely, we show for
      the first time in human neutrophils that selective inhibition of PAD4 potently
      prevents NETosis by all stimuli tested. Our data substantially extends current
      knowledge of the signaling pathways controlling NETosis, and reveals how they
      affect early or late stages of the phenomenon. In view of the involvement of NETs
      in several pathologies, our findings also identify molecular targets that could
      be exploited for therapeutic intervention.

PMID- 30279692
TI  - T Cells on Engineered Substrates: The Impact of TCR Clustering Is Enhanced by LFA
      1 Engagement.
AB  - We created APC-mimetic synthetic substrates to study the impact of ligand
      clustering on T cell activation and spreading. The substrates exhibit antibodies
      directed against the TCR-complex in the form of a patterned array of sub
      micrometric dots surrounded by a fluid supported lipid bilayer (SLB) which may
      itself be functionalized with another bio-molecule. We show that for T cell
      adhesion mediated by T cell receptor (TCR) alone, in the patterned, but not in
      the corresponding homogeneous controls, the TCR, ZAP-70 and actin are present in
      the form of clusters or patches that co-localize with the ligand-dots. However,
      global cell scale parameters like cell area and actin distribution are only
      weakly impacted by ligand clustering. In presence of ICAM-1 - the ligand of the T
      cell integrin LFA-1 - on the SLB, the TCR is still clustered due to the
      patterning of its ligands, but now global parameters are also impacted. The actin
      organization changes to a peripheral ring, resembling the classical actin
      distribution seen on homogeneous substrates, the patterned membrane topography
      disappears and the membrane is flat, whereas the cell area increases
      significantly. These observations taken together point to a possible pivotal role
      for LFA-1 in amplifying the effect of TCR-clustering. No such effect is evident
      for co-engagement of CD28, affected via its ligand B7.2. Unlike on ICAM-1, on
      B7.2 cell spreading and actin organization are similar for homogeneous and
      patterned substrates. However, TCR and ZAP-70 clusters are still formed in the
      patterned case. These results indicate complementary role for LFA-1 and CD28 in
      the regulation and putative coupling of TCR micro-clusters to actin. The
      engineered substrates presented here clearly have the potential to act as
      platform for fundamental research in immune cell biology, as well as
      translational analyses in immunotherapy, for example to screen molecules for
      their role in T cell adhesion/activation.

PMID- 30279693
TI  - Unraveling Rice Tolerance Mechanisms Against Schizotetranychus oryzae Mite
      Infestation.
AB  - Rice is the staple food for over half of the world's population. Infestation of
      Schizotetranychus oryzae (Acari: Tetranychidae) causes great losses in rice
      productivity. To search for rice genotypes that could better tolerate S. oryzae
      infestation, we evaluated morphological and production parameters in Brazilian
      cultivars, and identified two cultivars with contrasting responses. Leaf damage
      during infestation was similar for all cultivars. However, infestation in Puita
      INTA-CL resulted in reduction in the number of seeds per plant, percentage of
      full seeds, weight of 1,000 seeds, and seed length, whereas infestation in IRGA
      423 increased weight of 1,000 seeds and seed length. Reduction in seed weight per
      plant caused by infestation was clearly higher in Puita INTA-CL (62%) compared to
      IRGA 423 (no reduction detected), thus Puita INTA-CL was established as
      susceptible, and IRGA 423 as tolerant to S. oryzae infestation. Photosynthetic
      parameters were less affected by infestation in IRGA 423 than in Puita INTA-CL,
      evidencing higher efficiency of energy absorption and use. S. oryzae infestation
      also caused accumulation of H2O2, decreased cell membrane integrity (indicative
      of cell death), and accelerated senescence in leaves of Puita INTA-CL, while
      leaves of IRGA 423 presented higher levels of total phenolics compounds. We
      performed proteomics analysis of Puita INTA-CL and IRGA 423 leaves after 7 days
      of infestation, and identified 60 differentially abundant proteins (28 more
      abundant in leaves of Puita INTA-CL and 32 in IRGA 423). Proteins related to
      plant defense, such as jasmonate synthesis, and related to other mechanisms of
      tolerance such as oxidative stress, photosynthesis, and DNA structure
      maintenance, together with energy production and general metabolic processes,
      were more abundant in IRGA 423. We also detected higher levels of silicon (as
      amorphous silica cells) in leaves of infested IRGA 423 plants compared to Puita
      INTA-CL, an element previously linked to plant defense, indicating that it could
      be involved in tolerance mechanisms. Taken together, our data show that IRGA 423
      presents tolerance to S. oryzae infestation, and that multiple mechanisms might
      be employed by this cultivar. These findings could be used in biotechnological
      approaches aiming to increase rice tolerance to mite infestation.

PMID- 30279691
TI  - Mathematical Analysis of Cytokine-Induced Differentiation of Granulocyte-Monocyte
      Progenitor Cells.
AB  - Granulocyte-monocyte progenitor (GMP) cells play a vital role in the immune
      system by maturing into a variety of white blood cells, including neutrophils and
      macrophages, depending on exposure to cytokines such as various types of colony
      stimulating factors (CSF). Granulocyte-CSF (G-CSF) induces granulopoiesis and
      macrophage-CSF (M-CSF) induces monopoiesis, while granulocyte/macrophage-CSF (GM
      CSF) favors monocytic and granulocytic differentiation at low and high
      concentrations, respectively. Although these differentiation pathways are well
      documented, the mechanisms behind the diverse behavioral responses of GMP cells
      to CSFs are not well understood. In this paper, we propose a mechanism of
      interacting CSF-receptors and transcription factors that control GMP
      differentiation, convert the mechanism into a set of differential equations, and
      explore the properties of this mathematical model using dynamical systems theory.
      Our model reproduces numerous experimental observations of GMP cell
      differentiation in response to varying dosages of G-CSF, M-CSF, and GM-CSF. In
      particular, we are able to reproduce the concentration-dependent behavior of GM
      CSF induced differentiation, and propose a mechanism driving this behavior. In
      addition, we explore the differentiation of a fourth phenotype, monocytic myeloid
      derived suppressor cells (M-MDSC), showing how they might fit into the classical
      pathways of GMP differentiation and how progenitor cells can be primed for M-MDSC
      differentiation. Finally, we use the model to make novel predictions that can be
      explored by future experimental studies.

PMID- 30279695
TI  - Malaysian Carica papaya L. var. Eksotika: Current Research Strategies Fronting
      Challenges.
AB  - Carica papaya L. or commonly known as papaya, is a major tropical crop consumed
      worldwide either as a vegetable or fresh fruit or processed products. In
      Malaysia, papaya was initially planted as a smallholder crop throughout the
      country. Eventually after 15 years of breeding and selection, a new variety,
      named C. papaya L. var. Eksotika, was released by the Malaysian Agricultural
      Research and Development Institute (MARDI) in 1987. This event changed the
      outlook of papaya planting from a smallholder crop to a plantation crop. Despite
      the blooming papaya business, the industry faced various disease issues that
      jeopardize its future. The most devastating was the papaya dieback disease, which
      affected approximately 800 hectares of plantation, destroyed approximately 1
      million trees nationwide with total losses estimated at US$ 58 million. Even
      though Eksotika is a favored commercial variety with good eating and aesthetic
      quality fruit, its potential for more lucrative distant markets is tarnished with
      its short-shelf life fruits. Several strategies had been reported to address the
      challenges faced by Eksotika specifically against the dieback disease and the
      fruit's short shelf-life. This review focuses on C. papaya L. var. Eksotika
      particularly on the strategies to address the challenges faced in order to
      sustain the economic value of this crop plant, which had contributed
      significantly to the Malaysian economy.

PMID- 30279694
TI  - Light, Ethylene and Auxin Signaling Interaction Regulates Carotenoid Biosynthesis
      During Tomato Fruit Ripening.
AB  - Light signaling and plant hormones, particularly ethylene and auxins, have been
      identified as important regulators of carotenoid biosynthesis during tomato fruit
      ripening. However, whether and how the light and hormonal signaling cascades
      crosstalk to control this metabolic route remain poorly elucidated. Here, the
      potential involvement of ethylene and auxins in the light-mediated regulation of
      tomato fruit carotenogenesis was investigated by comparing the impacts of light
      treatments and the light-hyperresponsive high pigment-2 (hp2) mutation on both
      carotenoid synthesis and hormonal signaling. Under either light or dark
      conditions, the overaccumulation of carotenoids in hp2 ripening fruits was
      associated with disturbed ethylene production, increased expression of genes
      encoding master regulators of ripening and higher ethylene sensitivity and
      signaling output. The increased ethylene sensitivity observed in hp2 fruits was
      associated with the differential expression of genes encoding ethylene receptors
      and downstream signaling transduction elements, including the downregulation of
      the transcription factor ETHYLENE RESPONSE FACTOR.E4, a repressor of carotenoid
      synthesis. Accordingly, treatments with exogenous ethylene promoted carotenoid
      biosynthetic genes more intensively in hp2 than in wild-type fruits. Moreover,
      the loss of HP2 function drastically altered auxin signaling in tomato fruits,
      resulting in higher activation of the auxin-responsive promoter DR5, severe down
      regulation of AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) genes and altered accumulation
      of AUXIN RESPONSE FACTOR (ARF) transcripts. Both tomato ARF2 paralogues (Sl-ARF2a
      and SlARF2b) were up-regulated in hp2 fruits, which agrees with the promotive
      roles played by these ARFs in tomato fruit ripening and carotenoid biosynthesis.
      Among the genes differentially expressed in hp2 fruits, the additive effect of
      light treatment and loss of HP2 function was particularly evident for those
      encoding carotenoid biosynthetic enzymes, ethylene-related transcription factors,
      Aux/IAAs and ARFs. Altogether, the data uncover the involvement of ethylene and
      auxin as part of the light signaling cascades controlling tomato fruit metabolism
      and provide a new link between light signaling, plant hormone sensitivity and
      carotenoid metabolism in ripening fruits.

PMID- 30279696
TI  - Dietary Oxidative Balance Scores and Biomarkers of Inflammation among Individuals
      with and without Chronic Kidney Disease.
AB  - Background: Oxidative stress and inflammation are proposed mechanisms of
      nonspecific kidney injury and progressive kidney failure. Higher dietary
      oxidative balance scores (OBS) are associated with lower prevalence of chronic
      kidney disease (CKD). Methods: We investigated the association between OBS and
      biomarkers of inflammation using data from the Reasons for Geographic and Racial
      Differences in Stroke (REGARDS) study. Nutrient estimates from the Block Food
      Frequency Questionnaires were used to define tertiles of 11 pro- and antioxidant
      factors. Points for each OBS component were summed, with a higher score
      indicating predominance of antioxidant exposures. Multivariable linear regression
      models were used to estimate the association between OBS and biomarkers of
      inflammation (interleukin-6 [IL-6], interleukin-8 [IL-8], interleukin-10 [IL-10],
      fibrinogen, C-reactive protein [CRP], white blood cell count, and cystatin C). An
      interaction term was included to determine if associations between OBS and
      inflammatory markers differed between individuals with and without CKD. Results:
      Of 682 participants, 22.4% had CKD. In adjusted models, OBS was associated with
      CRP and IL-6. For every 5-unit increase in OBS, the CRP concentration was -15.3%
      lower (95% CI: -25.6, -3.6). The association of OBS with IL-6 differed by CKD
      status; for every 5-unit increase in OBS, IL-6 was -10.7% lower (95% CI: -16.3, 
      4.7) among those without CKD, but there was no association among those with CKD
      (p = 0.03). Conclusion: This study suggests that a higher OBS is associated with
      more favorable levels of IL-6 and CRP, and that the association of OBS and IL-6
      may be modified by CKD status.

PMID- 30279697
TI  - Cognitive Deficits and Associated ERP N400 Abnormalities in FXTAS With
      Parkinsonism.
AB  - Objective: To examine cognitive deficits and associated brain activity in fragile
      X-associated tremor/ataxia syndrome (FXTAS) patients with parkinsonism (FXTp+),
      in relation to FXTAS patients without parkinsonism (FXTp-), and normal elderly
      controls (NC). Methods: Retrospective reviews were performed in 65 FXTAS patients
      who participated in the event-related brain potential (ERP) study and also had
      either a videotaped neurological examination or a neurological examination for
      extrapyramidal signs. Parkinsonism was defined as having bradykinesia with at
      least one of the following: rest tremor, postural instability, hypermyotonia, or
      rigidity. Eleven FXTp+ patients were identified and compared to 11 matched FXTp-
      and 11 NC. Main ERP measures included the N400 congruity effect, N400 repetition
      effect, and the late positive component (LPC) repetition effect. Results: When
      compared with FXTp- and NC, the FXTp+ group showed more severe deficits in
      executive function, cued-recall, recognition memory, along with a significantly
      reduced N400 repetition effect (thought to index semantic processing and verbal
      learning/memory) which was correlated with poorer verbal memory. Across all
      patients, FMR1 mRNA levels were inversely correlated with delayed recall on the
      California Verbal Learning Test (CVLT). Interpretation: The findings of more
      prominent executive dysfunction and verbal learning/memory deficits in FXTp+ than
      FXTp- are consistent with findings in Parkinson's disease (PD), and may indicate
      that concomitant and/or synergistic pathogenetic mechanisms associated with PD
      play a role in FXTAS. These results have implications not only for understanding
      the cognitive impairments associated with the parkinsonism subtype of FXTAS, but
      also for the development of new interventions for these patients.

PMID- 30279698
TI  - Prioritized High-Confidence Risk Genes for Intellectual Disability Reveal
      Molecular Convergence During Brain Development.
AB  - Dissecting the genetic susceptibility to intellectual disability (ID) based on de
      novo mutations (DNMs) will aid our understanding of the neurobiological and
      genetic basis of ID. In this study, we identify 63 high-confidence ID genes with
      q-values < 0.1 based on four background DNM rates and coding DNM data sets from
      multiple sequencing cohorts. Bioinformatic annotations revealed a higher burden
      of these 63 ID genes in FMRP targets and CHD8 targets, and these genes show
      evolutionary constraint against functional genetic variation. Moreover, these ID
      risk genes were preferentially expressed in the cortical regions from the early
      fetal to late mid-fetal stages. In particular, a genome-wide weighted co
      expression network analysis suggested that ID genes tightly converge onto two
      biological modules (M1 and M2) during human brain development. Functional
      annotations showed specific enrichment of chromatin modification and
      transcriptional regulation for M1 and synaptic function for M2, implying the
      divergent etiology of the two modules. In addition, we curated 12 additional
      strong ID risk genes whose molecular interconnectivity with known ID genes (q
      values < 0.3) was greater than random. These findings further highlight the
      biological convergence of ID risk genes and help improve our understanding of the
      genetic architecture of ID.

PMID- 30279700
TI  - SUMO-Targeted Ubiquitin Ligases (STUbLs) Reduce the Toxicity and Abnormal
      Transcriptional Activity Associated With a Mutant, Aggregation-Prone Fragment of
      Huntingtin.
AB  - Cell viability and gene expression profiles are altered in cellular models of
      neurodegenerative disorders such as Huntington's Disease (HD). Using the yeast
      model system, we show that the SUMO-targeted ubiquitin ligase (STUbL) Slx5
      reduces the toxicity and abnormal transcriptional activity associated with a
      mutant, aggregation-prone fragment of huntingtin (Htt), the causative agent of
      HD. We demonstrate that expression of an aggregation-prone Htt construct with 103
      glutamine residues (103Q), but not the non-expanded form (25Q), results in severe
      growth defects in slx5Delta and slx8Delta cells. Since Slx5 is a nuclear protein
      and because Htt expression affects gene transcription, we assessed the effect of
      STUbLs on the transcriptional properties of aggregation-prone Htt. Expression of
      Htt 25Q and 55Q fused to the Gal4 activation domain (AD) resulted in reporter
      gene auto-activation. Remarkably, the auto-activation of Htt constructs was
      abolished by expression of Slx5 fused to the Gal4 DNA-binding domain (BD-Slx5).
      In support of these observations, RNF4, the human ortholog of Slx5, curbs the
      aberrant transcriptional activity of aggregation-prone Htt in yeast and a variety
      of cultured human cell lines. Functionally, we find that an extra copy of SLX5
      specifically reduces Htt aggregates in the cytosol as well as chromatin
      associated Htt aggregates in the nucleus. Finally, using RNA sequencing, we
      identified and confirmed specific targets of Htt's transcriptional activity that
      are modulated by Slx5. In summary, this study of STUbLs uncovers a conserved
      pathway that counteracts the accumulation of aggregating, transcriptionally
      active Htt (and possibly other poly-glutamine expanded proteins) on chromatin in
      both yeast and in mammalian cells.

PMID- 30279699
TI  - Epigenetics and Metabolism in Health and Disease.
AB  - In the next 10 years, one billion people are estimated to suffer from disabling
      consequences of metabolic disorders, making them the number one noncommunicable
      disease on a global scale by 2030. Lots of risk factors such as dietary intake,
      lack of exercise and other life style behaviors are considered to play a role in
      the development of metabolic disorders. Despite the efforts that have been
      undertaken to unravel their potential causes, the underlying molecular mechanisms
      remain elusive. Evidence suggests that the pathogenesis involves changes on
      chromatin and chromatin-modifying enzymes, which can contribute to a persistent
      dysregulated metabolic phenotype. Indeed, a rising number of studies links
      epigenetic alterations with the diagnosis and prognosis of metabolic disorders. A
      prerequisite for exploiting these findings for pharmacological intervention is a
      detailed understanding of how differential epigenetic modifications control cell
      metabolism. In this mini review, we summarize the recent advances in uncovering
      the interplay between epigenetics and metabolic pathways on a cellular level and
      highlight potential new avenues for alternative treatment strategies.

PMID- 30279703
TI  - Corrigendum: Emergence of Members of TRAF and DUB of Ubiquitin Proteasome System
      in the Regulation of Hypertrophic Cardiomyopathy.
AB  - [This corrects the article DOI: 10.3389/fgene.2018.00336.].

PMID- 30279701
TI  - Rapid Intraspecific Diversification of the Alpine Species Saxifraga sinomontana
      (Saxifragaceae) in the Qinghai-Tibetan Plateau and Himalayas.
AB  - An increasing number of phylogeographic studies have been conducted for plant
      species in the Qinghai-Tibetan Plateau (QTP) and its flanking mountains. However,
      these studies have mainly focused on the determination of glacial refugia and
      routes of inter-/post-glacial expansions. Rapid intraspecific diversification of
      plants in this region have not been thoroughly discussed. Herein, we investigate
      the effects of the Quaternary climate changes on population genetic structure and
      diversifications of a herbaceous alpine species, Saxifraga sinomontana, which may
      have an evolutionary time scale <5 million years in the QTP and Himalayan
      regions. Using a total of 350 individuals from 29 populations, we studied the
      evolutionary history of S. sinomontana by analyzing cpDNA trnL-trnF, rpl16 and
      nrDNA ITS sequences. A total of 89 haplotypes and 158 genotypes were detected for
      cpDNA and ITS sequences, respectively. Only a few haplotypes/genotypes were
      widespread, while an extremely large number of haplotypes/genotypes were
      restricted to single populations, which were scattered throughout the current
      geographical range of S. sinomontana. This suggests the existence of microrefugia
      of this species during the Quaternary glaciations. In addition, the relationships
      of the haplotypes/genotypes were almost completely not resolved by phylogenetic
      reconstruction. Combining characteristics in terms of high haplotype richness,
      large proportion of private haplotypes, and shallow haplotype divergence, we
      speculate that recent intraspecific diversification has occurred in S.
      sinomontana. Molecular clock analysis estimated that the onset diversification
      within S. sinomontana to be 1.09 Ma (95% HPD = 0.80-1.45), coinciding with the
      extensive Quaternary glaciations on the QTP which started ca. 1.17 Ma. The
      Quaternary climatic oscillations may have triggered rapid intraspecific
      diversification in this QTP-Himalayan species. However, large niche breadth, as
      well as introgression/hybridization between the studied species and its closely
      related sympatric saxifrages, may also played a role to some extent on the
      current genetic structure of S. sinomontana, which need to be further studied.

PMID- 30279702
TI  - Analysis of Time-Series Gene Expression Data to Explore Mechanisms of Chemical
      Induced Hepatic Steatosis Toxicity.
AB  - Non-alcoholic fatty liver disease (NAFLD) represents a wide spectrum of disease,
      ranging from simple fatty liver through steatosis with inflammation and necrosis
      to cirrhosis. One of the most challenging problems in biomedical research and
      within the chemical industry is to understand the underlying mechanisms of
      complex disease, and complex adverse outcome pathways (AOPs). Based on a set of
      28 steatotic chemicals with gene expression data measured on primary hepatocytes
      at three times (2, 8, and 24 h) and three doses (low, medium, and high), we
      identified genes and pathways, defined as molecular initiating events (MIEs) and
      key events (KEs) of steatosis using a combination of a time series and pathway
      analyses. Among the genes deregulated by these compounds, the study highlighted
      OSBPL9, ALDH7A1, MYADM, SLC51B, PRDX6, GPAT3, TMEM135, DLGDA5, BCO2, APO10LA,
      TSPAN6, NEURL1B, and DUSP1. Furthermore, pathway analysis indicated deregulation
      of pathways related to lipid accumulation, such as fat digestion and absorption,
      linoleic and linolenic acid metabolism, calcium signaling pathway, fatty acid
      metabolism, peroxisome, retinol metabolism, and steroid metabolic pathways in a
      time dependent manner. Such transcription profile analysis can help in the
      understanding of the steatosis evolution over time generated by chemical
      exposure.

PMID- 30279704
TI  - Benign Enlargement of Subarachnoid Space in Infancy: "A Review with Emphasis on
      Diagnostic Work-Up".
AB  - Macrocephaly is one of the most frequent reasons for referral to a pediatric
      neurologist. Benign enlargement of subarachnoid space (BESS) in infancy is the
      most common cause of macrocephaly and characterized clinically with large head
      circumference, normal or mildly motor and language delay and increased
      cerebrospinal fluid (CSF) in the subarachnoid space with normal ventricles or
      mild ventriculomegaly. In this review, we describe the etiology, epidemiology,
      clinical presentation, pathogenesis, neuroimaging, differential diagnosis,
      treatment and outcome of this entity from current literature with emphasis on
      diagnostic work-up.

PMID- 30279705
TI  - The Effects of Constraint-Induced Movement Therapy on Functions of Cerebral Palsy
      Children.
AB  - Objectives: Constraint-Induced Movement Therapy (CIMT) is an intervention method
      that can enhance cerebral palsy (CP) children's hand function. CP is a pervasive
      and common disorder which affects many aspects of a child life. Hemiplegic CP
      affects one side of a child's hand and has great effect on child's independence.
      We investigated the CIMT's studies conducted in Iran, and indicated the
      effectiveness of CIMT on duration and children age? Materials & Methods: This
      systematic review was conducted using the electronic databases such as Medline
      PubMed, CINAHL, etc. performed from 1990 to 2016. Iranian and foreigner famous
      journals in the fields of pediatrics such as Iranian Journal of Pediatrics (IJP),
      Iranian Rehabilitation Journal (IRJ) and Google scholar with some specific
      keywords such as CP, CIMT, and occupational therapy were searched. Results:
      Overall, 43 articles were found, from which, 28 articles were removed because of
      lack of relevancy. Ten article were omitted because of duplication and exclusion
      criteria, so finally 15 articles were included. Conclusion: CIMT is effective
      compared to no intervention but there are some inconsistencies regarding some
      parts of CIMT effectiveness such as its effectiveness on muscle tone and
      protective extension.

PMID- 30279706
TI  - Clinical Trial of Efficacy Evaluation of Omega-3 with Risperidone on Seizures
      Frequency in Children with Refractory Epilepsy and Attention
      Deficit/Hyperactivity Disorder.
AB  - Objectives: We aimed to answer the question whether or not previous antiepileptic
      drugs with combination of omega-3 and risperidone are more efficient than
      previous antiepileptic drugs with risperidone alone in decreasing of seizures
      monthly frequency of children with refractory epilepsy and attention
      deficit/hyperactivity disorder (ADHD). Material & Methods: In a randomized
      clinical trial (IRCT201604212639N18), participants referred to Pediatric
      Neurology Clinic of Shahid Sadoughi Hospital, Yazd, Iran from Jun 2015 were
      distributed randomly into two groups. In group I, one capsule of omega-3 daily
      and 0.5 mg of risperidone was divided into two doses with previous antiepileptic
      drugs and in group II, 0.5 mg of risperidone was divided into two doses with
      previous antiepileptic drugs were given. The drugs use was continued for three
      months and the children were followed up monthly for three consecutive months.
      Primary outcomes included seizure monthly frequency and good response (more than
      50% of reduction in seizures monthly frequency). Secondary outcome was clinical
      side effects. Results: Overall, 23 girls and 33 boys with mean age of 9.24+0.15
      yr (29 children in omega-3 group and 27 children in control group) were
      evaluated. Omega-3 therapy was effective in decreasing of seizures monthly
      frequency (10.41+/-3.92 times vs. 17.01+/-4.98, P=0.03). Good response was seen
      in three children (11.1%) in control (95% confidence interval: 8%-22.8%) and in 9
      children (31%) in omega-3 (95% CI: 47.83%-14.17%) group, which showed that omega
      3 was more effective in seizure control. (P=0.001). Frequency of side effects was
      not different in the two groups (14.8 % in control vs. 20.7% in omega-3 groups,
      P=0.5). Conclusion: Omega-3 might be used as an effective and safe drug in
      seizures control of children with refractory epilepsy and ADHD.

PMID- 30279707
TI  - Autistic Children Are More Responsive to Tactile Sensory Stimulus.
AB  - Objective: This research was an experimental study that was aimed to detect
      differences response of tactile sensory stimulus between normal children and
      children with sensory brain development disorders such as Autism Spectrum
      Disorder (ASD). Materials & Methods: A total of 134 children, in two groups
      including 67 healthy children (control) and 67 children with autism were studied.
      Tactile sensory stimulus responses in children were tested directly using a
      Reflex Hammer. In addition, tactile sensory sensitivity was also assessed via
      questionnaire Short Sensory Profile (SSP) filled out by the child's parents. All
      response data were analyzed using Fisher's Exact Test; questionnaire data was
      analyzed with the Mann-Whitney U Test. Results: Autistic children were more
      sensitive to palpation and pain than children who were not autistic. Furthermore,
      the value of SSP was also significantly higher (P<0.05) in autistic children,
      which means that they always responded to all categories in the SSP questionnaire
      than children who are not autistic. Conclusion: Autistic children are more
      sensitive to tactile sensory stimulus and all categories of SSP than children who
      are not autistic.

PMID- 30279708
TI  - Comparison of the Quality of Sleep and Intensity of Headache between Migraine,
      Tension Headache, and Healthy Children.
AB  - Objectives: Headache and sleep problems are commonly reported in children, and
      both can adversely impact the child's life. We aimed to compare the sleep quality
      and intensity of headache between school-age children with migraine as well as
      tension headache and healthy children. Materials & Methods: In this cross
      sectional study, 198 children 6-12 yr old in three groups were enrolled from Aug
      2015 to Mar 2016. Migraine and tension headache groups from the Outpatient Clinic
      of Imam Khomeini of Hamadan, western Iran and healthy group from elementary
      schools were randomly selected (66 children in each group). Data were collected
      using demographic questionnaire, Child Sleep Habits Questionnaire (CSHQ), Numeric
      Scale of Pain Intensity and Wong-Baker Faces Pain Rating Scale. The data were
      analyzed using SPSS by descriptive statistic and multivariate ANOVA, one way
      ANOVA, Chi-square, Kruskal-Wallis and linear regression tests. Results:
      Approximately, 45.5% of children with migraine and 37.9% of them with tension
      headache had experienced severe headache. Only a significant relationship was
      seen between mean scores of headache intensity and sleep quality in migraine
      group (P<0.05). There was a significant difference in mean scores of sleep
      quality among three groups (P<0.001). Conclusion: The children with migraine
      experienced more unsuitable sleep in duration of severe headache. Highlighting
      the co-morbidity between intensity of headache and sleep problem of children with
      migraine and tension headache is important to improve treatment strategies and to
      know the impact of headache on their normal life.

PMID- 30279709
TI  - The Effect of Non-Nutritive Sucking and Maternal Milk Odor on the Independent
      Oral Feeding in Preterm Infants.
AB  - Objectives: Given the positive effects of stimulation with breast milk odor and
      non-nutritive sucking (NNS) on preterm feeding skills, we examined the effect of
      NNS and milk odor, on the time of achieving independent oral feeding in preterm
      infants. Materials & Methods: This study was conducted at two Neonatal Intensive
      Care Units of Tehran, Iran in 2016. Overall, 32 neonates with gestational ages of
      28-32 wk were enrolled in two groups; NNS with and without olfactory stimuli
      (breast milk odor). The simulations were performed in both groups during the
      first five minutes of gavage, three times per day, and over ten consecutive days.
      Weight gain, time of achieving oral feeding and chronological age at discharge
      were as measures of the effectiveness of the interventions. The results of the
      interventions were analyzed and compared using SPSS.18. Results: NNS with breast
      milk odor resulted to a lower post-menstrual age at the first oral feeding,
      independent oral feeding and discharge from the hospital, but had no effects on
      their daily weight gain and weight at the time of discharge. Conclusion: These
      results show the effectiveness of combining milk odor and NNS as two important
      stimuli in achieving oral feeding and earlier discharge from the hospital.

PMID- 30279710
TI  - A Web-Based Caring Training for Caregivers of Children with Cerebral Palsy:
      Development and Evaluation.
AB  - Objectives: Caregivers of children with cerebral palsy (CP) have to spend a long
      time to take care of their children. We aimed to develop a user-friendly web
      based intervention for training parents of children with CP and evaluate the
      process of development using modified CeHRes roadmap. Materials & Methods: The
      study was conducted from September 2016 to September 2017 in Tehran, Iran. We did
      it in four main steps including determining the needs of users, content
      development, design, operational development and evaluation. Results: The website
      for caregiver training provided nine general topics and had the possibility that
      the caregivers could determine their educational priorities. Moreover, the users
      could share their experiences with other users and could ask questions from an
      expert. Ten caregivers completed a usability questionnaire after four weeks of
      use. The average score of 70.5 out of 100 was shown among caregivers. The average
      score of all statements was above three on a Likert scale between 1 and 5.
      Conclusion: The website has the possibilities including registering caregivers of
      children with CP, the possibility to confirm registration with an SMS and the
      possibility to determine the caregiver educational priorities. It has the
      usability for training caregivers of children with CP.

PMID- 30279711
TI  - Comparison of the Effect of Phenobarbital versus Sodium Valproate in Management
      of Children with Status Epilepticus.
AB  - Objectives: Acute prolonged seizure is the most common neurological emergency in
      children. This research was conducted to compare the effect of intravenous
      phenobarbital and Sodium valproate in control of seizure in children with status
      epilepticus, referred to emergency ward from Mar to Nov 2013. Materials &
      Methods: In this randomized clinical trial, registered with the code number
      IRCT2015051722300N1, 80 children aged 6 months to 10 years with prolonged seizure
      and with no response to one dose of diazepam (0.2 mg/kg) administered through IV
      injection during the five min were selected. Children were randomly divided into
      two groups, intervention, and control through permutation blocks. In intervention
      group, intravenous Sodium valproate (20 mg/kg) and in control group, intravenous
      phenobarbital (20 mg/kg) were prescribed. Data such as age, gender, history of
      previous seizure, seizure type, and recovery time after receiving drug was
      recorded in the form. Data analysis was done through descriptive statistics, Chi
      square and Independent t- test. Results: Two groups were the same in terms of age
      and gender and had no statistically significant difference, but they were
      different in terms of seizure type. In valproate group, 18 patients (45%) and in
      phenobarbital group, 32 patients (80%) had positive response to the treatment and
      the chi-square test showed the significant difference. Conclusion: With regards
      to this point that in phenobarbital group, patients had more rapid response to
      drug in comparison with patients in Sodium valproate group, phenobarbital is a
      suitable and effective drug for controlling of seizure in children.

PMID- 30279712
TI  - Goodenough-Harris Drawing a Man Test (GHDAMT) as a Substitute of Ages and Stages
      Questionnaires (ASQ2) for Evaluation of Cognition.
AB  - Objective: The main aim of the current research was evaluation of concurrent
      validity of the Goodenough-Harris Draw-A-Man Test (GHDAMT) with the problem
      solving subscale of ASQ2 among children between 54-60 months old in Tabriz City,
      northwestern Iran. Materials & Methods: In this cross-sectional study, 136 males
      and 105 females were selected by simple random sampling from nursery schools in
      Tabriz City, northwestern Iran in 2014 and tested with GHDAMT and ASQ2 to compare
      the concurrent validity of these tests in evaluation of cognition. Data were
      analyzed using Pearson or Spearman correlation coefficients and SPSS.16. Results:
      The mean Intelligence Quotient (IQ) in girls was 128+/-18.18 and in boys 118+/
      18.50, and the difference was statistically significant P<0.001. There was no
      statistically significant correlation between GHDAMT and ASQ2 .The statistical
      correlation was significant between IQ and mental age among children who had -2SD
      score in problem-solving subscale, but there was no statistical correlation
      between children who had -1SD score P<0.002. There was no statistically
      significant correlation between problem-solving subscale of ASQ2 and mental age
      and IQ. Conclusion: GHDAMT did not have acceptable validity and concurrent
      validity of the test was less than 0.3. So GHDAMT cannot be used as a substitute
      of ASQ questionnaire. However, the correlation of two tests in children with
      intellectual and developmental disability was significant. After doing more
      studies in further research, it is possible to use GHDAMT as a proper tool for
      cognition evaluation of these children.

PMID- 30279713
TI  - Oral Levetiracetam as Add-On Therapy in Refractory Neonatal Seizures.
AB  - Objective: Seizure is the most common signs of nervous system disease in
      neonates. The first line of treatments in neonatal seizures (after ruling out and
      emergency treatment of electrolyte imbalance and hypoglycemia) are phenobarbital
      and phenytoin. We aimed to evaluate drugs that are more effective on neonatal
      seizure. Materials & Methods: Patients admitted to neonatal wards & NICUs (level 
      IIa&  IIb) in Qom hospitals (2015-2017), central Iran with presentation of
      seizure, were enrolled in this clinical trial study. After ruling out electrolyte
      imbalance and hypoglycemia these neonates were managed by intravenous
      phenobarbital, then if no response was seen we added intravenous phenytoin and
      for remaining neonates with refractory seizure we applied oral levetiracetam as
      add on therapy. The study was registered as code number of IRCT2016051527896N1.
      Results: Initially, 245 neonates were enrolled. According to exclusion criteria,
      12 cases were excluded, and phenobarbital was prescribed to the remaining
      patients. Out of these, 86 patients did not respond, and phenytoin was prescribed
      for them. Forty two patients who were not responding to phenytoin were finally
      treated with oral levetiracetam. Finally, 95.3% of seizures were controlled with
      oral levetiracetam but 4.7% were not cured. Conclusion: When the intravenous form
      of levetiracetam is not available and neonatal seizure does not respond to first
      line classic drugs, oral levetiracetam as add on therapy maybe effective.

PMID- 30279714
TI  - A Novel Splice Site Mutation of the ATM Gene Associated with Ataxia
      Telangiectasia.
AB  - Objectives: Ataxia telangiectasia (AT) is a rare autosomal recessive disorder
      caused by mutation in the Ataxia telangiectasia mutated (ATM) gene. This disorder
      is characterized by progressive cerebellar ataxia, telangiectasia,
      immunodeficiency and a predisposition to leukemia/lymphoma. In this study, we
      investigated a family with a new mutation in ATM, confirmed by molecular genetic
      test. Materials&Methods: Four members of a family including a symptomatic AT
      patient, his parents and sibling were examined for ATM gene defects at Kerman
      University Hospital, Kerman, Iran in 2016. DNA was extracted from peripheral
      leukocytes and the coding regions and exon-intron boundaries of ATM gene were
      amplified by next-generation sequencing technique. The identified mutation was
      tested in all members of the family. Results: Molecular analyses identified a
      homozygous T to G substitution in c.7308-6 position resulting in a novel acceptor
      splice site in intron 49 of the ATM gene in the index patient. Parents and
      sibling of the proband were heterozygous for the same mutation. Conclusion: The
      variant c.7308-6T>G is predicted to be pathogenic due to impaired splice site
      causing exon skipping. This newly found frameshift mutation cosegregated as an
      autosomal recessive trait as expected for Ataxia telangiectasia syndrome.

PMID- 30279715
TI  - The Relation between Urinary Tract Infection and Febrile Seizure.
AB  - Objectives: Febrile seizure is the most common type of seizure among children.
      Identification of factors involved in febrile seizure is highly critical. The
      present study was conducted to determine the association between children's
      urinary tract infection and febrile seizure. Materials & Methods: In this case
      control study, 165 children with simple febrile seizure (case group) were
      compared with 165 children with fever and without seizure (control group) in
      terms of urinary tract infection (UTI) in Qazvin, central Iran in 2015-2016. The
      age of children was between 6 months to 5 yr. Results: Among 165 children with
      febrile seizure, 25 (15.2%) had urinary tract infection. In the control group,
      only 2 patients (1.2%) had UTI. There was significant difference between two
      groups regarding urinary tract infection (P=0.001). Among 25 children with UTI in
      the case group, 17 children (68%) had acute pyelonephritis, and the remaining 8
      children (32%) had cystitis. The two patients with UTI in control group had
      cystitis (P=0.055). Conclusion: Urinary tract infection could be a risk factor
      for febrile seizure. Therefore, all patients with febrile seizure are examined in
      terms of urinary tract infection.

PMID- 30279716
TI  - A look at the normal development of Pointing and Reaching Gestures in 12-16-Month
      Old Farsi-Speaking Children: A Longitudinal Study.
AB  - Objectives: Human beings can use gestures such as pointing and reaching to
      communicate with others before they have the ability to use verbal communication
      to produce speech. Given the importance of children's communication development
      and the key role of gestures development in communicating, the main purpose of
      this study was to analyze the normal development of pointing and reaching
      gestures and their relationship in 12-16-month-old children speaking Farsi.
      Materials & Methods: In this prospective, observational and longitudinal study
      the gestures of 11 monolingual Farsi-speaking children (7 boys and 4 girls, from
      Oct 2015 to Jan 2017 in the homes of participants across Tehran, Iran) were
      evaluated via non-randomized sampling method. Child-mother interactions were
      videotaped monthly in a semi-structured context to capture the emergence and
      consistent use of targeted gestures. Afterward, the data were coded and
      statistically analyzed for this purpose Repetitive measured; independent t-test
      and Pearson correlation were used. Results: The mean of the pointing gesture
      increased significantly from 12 to 16 months (P<0.05). However, this was not
      significant for the reaching gesture. Moreover, there was no relationship between
      pointing and reaching gestures. Conclusion: Pointing gestures increase with age
      from 12-16 months in Farsi-speaking children. However, reaching gestures stay the
      same between 12-16 months of age. The study provided rich details of common
      gestures that children use to signal their intentions before verbal
      communication.

PMID- 30279717
TI  - The Relationship between Emotional Content and Word Processing in Normal Persian
      Speaking Children.
AB  - Objectives: Emotion is a key component in language processing, but emotional
      words processing in children is still controversial. We aimed to investigate the
      relationship between emotional dimensions, arousal and valence, word familiarity,
      comprehension, use, and emotional content recognition. Eventually, a list of
      emotional content words for this age was prepared in Persian. Materials&Methods:
      The study was conducted in selected elementary schools in Tehran, Iran from April
      to June 2017. Emotional words, from adult emotional words list, were categorized
      into 5 groups according to their arousal and valence scores, including neutral,
      happy, calm, anxious and sad. Evaluation of familiarity, use, comprehension and
      emotional content recognition of the list was conducted with a checklist in 60
      first grade children by speech and language pathologist. Results: Neutral words
      gained the highest score in familiarity, use, comprehension and emotional content
      recognition (the mean=0.74). Afterward, there were the emotional words with high
      valence, calm (the mean=0.64) and happy (the mean=0.52). Finally, it was found
      the low score for valence emotional words, sad (the mean=0.46) anxious (the mean
      =0.43) in end of score rating. There was a significant difference between all
      word groups in four aspects (P-value<0.001). There were no significant
      differences between boys and girls in four aspects. Conclusion: Neutral words are
      better comprehended and expressed than emotional words. Valence is more effective
      than arousal in emotional words. Gender was not a determinant factor in all of
      the aspects. An emotional word list which is comprehensible for children in
      Persian language was prepared.

PMID- 30279718
TI  - Risk Factors for Hearing Loss and Its Prevalence in Neonates Older than 6 Months
      with History of Hospitalization in Intensive Care Unit.
AB  - Objectives: Hearing loss is one of the most important disabilities in neonates.
      Delay in the detection of hearing loss leads to impaired development and may
      prevent the acquisition of speech. We aimed to determine the risk factors
      associated with hearing loss in neonatal patients aged more than 6 months with a
      history of hospitalization in Neonatal Intensive Care Unit (NICU). Methods: In
      this case-control study, screening for hearing loss was carried out on 325
      neonates aged 6-12 months referred to Pediatric Neurology Office of Vali-e-Asr
      Hospital, Tehran, Iran up to 2011. Hearing loss was confirmed using Auditory
      Brainstem Response screening test (ABR). Results: The prevalence of mildly and
      moderately hearing loss in neonates was determined as 3.6%. The most significant
      risk factors for hearing loss in neonates were neonatal icterus associated with
      phototherapy, respiratory distress syndrome (RDS) and lower Apgar score.
      Conclusion: It seems to quantitative auditory system screening using ABR is
      necessary for all neonates; because rehabilitation support such as speech therapy
      and hearing training in this age period is more effective than older ages.

PMID- 30279719
TI  - Cockayne Syndrome Misdiagnosed as Cerebral Palsy.
AB  - A 7-yr-old patient was referred to pediatric orthopedic clinic of Imam hospital
      (2016) with the diagnosis of cerebral palsy (CP). His parents were concerned
      about some inconsistency of his disease progression. After initial evaluations,
      the diagnosis of CP was incorrect. The true diagnosis was suspected and confirmed
      with molecular genetic analysis. A rare autosomal recessive disorder -Cockayne
      syndrome- was diagnosed. Although untreatable, it can be prevented by appropriate
      prenatal diagnostic tests for their future children.

PMID- 30279720
TI  - Enterobacter Meningitis Due To Dermoid Cyst Manipulation.
AB  - Gram-negative meningitis can occurssubsequent to dura-arachnoid barrier
      disruption because of trauma, surgery and rarely an infected dermoid cyst.
      Association of neurosurgical procedures with Gram-negative meningitis was
      described for the first time in 1940. Intracranial infections from gram-negative
      bacilli like Enterobacter are serious and difficult to treat as many antibiotics
      fail to achieve bactericidal concentrations in the cerebrospinal fluid. Here in,
      we report a rare case of pediatric Enterobacter meningitis in a patient with a
      dermoid cyst that had been manipulated. She was managed with antibiotic therapy
      plus surgical removal of the infected cyst.

PMID- 30279721
TI  - Offspring dependence on parental care and the role of parental transfer of oral
      fluids in burying beetles.
AB  - Background: Immature stages of many animals can forage and feed on their own,
      whereas others depend on their parents' assistance to obtain or process food. But
      how does such dependency evolve, and which offspring and parental traits are
      involved? Burying beetles (Nicrophorus) provide extensive biparental care,
      including food provisioning to their offspring. Interestingly, there is
      substantial variation in the reliance of offspring on post-hatching care among
      species. Here, we examine the proximate mechanisms underlying offspring
      dependence, focusing on the larvae of N. orbicollis, which are not able to
      survive in the absence of parents. We specifically asked whether the high
      offspring dependence is caused by (1) a low starvation tolerance, (2) a low
      ability to self-feed or (3) the need to obtain parental oral fluids. Finally, we
      determined how much care (i.e. duration of care) they require to be able to
      survive. Results: We demonstrate that N. orbicollis larvae are not characterized
      by a lower starvation tolerance than larvae of the more independent species.
      Hatchlings of N. orbicollis are generally able to self-feed, but the efficiency
      depends on the kind of food presented and differs from the more independent
      species. Further, we show that even when providing highly dependent N. orbicollis
      larvae with easy ingestible liquefied mice carrion, only few of them survived to
      pupation. However, adding parental oral fluids significantly increased their
      survival rate. Finally, we demonstrate that survival and growth of dependent N.
      orbicollis larvae is increased greatly by only a few hours of parental care.
      Conclusions: Considering the fact that larvae of other burying beetle species are
      able to survive in the absence of care, the high dependence of N. orbicollis
      larvae is puzzling. Even though they have not lost the ability to self-feed, an
      easily digestible, liquefied carrion meal is not sufficient to ensure their
      survival. However, our results indicate that the transfer of parental oral fluids
      is an essential component of care. In the majority of mammals, offspring rely on
      the exchange of fluids (i.e. milk) to survive, and our findings suggest that even
      in subsocial insects, such as burying beetles, parental fluids can significantly
      affect offspring survival.

PMID- 30279722
TI  - Improved secretory expression of lignocellulolytic enzymes in Kluyveromyces
      marxianus by promoter and signal sequence engineering.
AB  - Background: Taking into account its thermotolerance, high growth rate, and broad
      substrate spectrum, Kluyveromyces marxianus can be considered an ideal
      consolidated bioprocessing (CBP). A major obstacle to ethanol production using K.
      marxianus is the low production of lignocellulolytic enzymes, which reduces the
      cellulose hydrolysis and ethanol production. Thus, further improvement of enzyme
      expression and secretion is essential. Results: To improve the expression of
      lignocellulolytic enzymes, the inulinase promoter and signal sequence from K.
      marxianus was optimized through mutagenesis. A T(-361)A mutation inside the
      promoter, a deletion of AT-rich region inside 5'UTR (UTR?A), and a P10L
      substitution in the signal sequence increased the secretory expression of the
      feruloyl esterase Est1E by up to sixfold. T(-361)A and UTR?A increased the mRNA
      expression, while the P10L substitution extended the hydrophobic core of signal
      sequence and promoted secretion of mature protein. P10L and T(-361)A mutations
      increased secretory expressions of other types of lignocellulolytic enzymes by up
      to threefold, including endo-1,4-beta-glucanase RuCelA, endo-1,4-beta
      endoxylanase Xyn-CDBFV, and endo-1,4-beta-mannanase MAN330. During the fed-batch
      fermentation of strains carrying optimized modules, the peak activities of
      RuCelA, Xyn-CDBFV, MAN330, and Est1E reached 24 U/mL, 25,600 U/mL, 10,200 U/mL,
      and 1220 U/mL, respectively. Importantly, higher yield of enzymes by optimized
      promoter and signal sequence were achieved in all tested carbon sources,
      including the major end products of lignocellulose saccharification and
      fermentation, with growth on xylose resulting in the highest production.
      Conclusions: The engineered promoter and signal sequence presented increased
      secretory expressions of different lignocellulolytic enzymes in K. marxianus by
      means of various carbon resources. Activities of lignocellulolytic enzymes in fed
      batch fermentation were the highest activities reported for K. marxianus so far.
      Our engineered modules are valuable in producing lignocellulolytic enzymes by K.
      marxianus and in constructing efficient CBP strains for cellulosic ethanol
      production.

PMID- 30279723
TI  - Combination of NIR therapy and regulatory T cell modulation using layer-by-layer
      hybrid nanoparticles for effective cancer photoimmunotherapy.
AB  - The efficacy of combined near-infrared (NIR) and immune therapies for inhibiting
      tumor growth and recurrence has gained increasing research attention. Regulatory
      T cells in the tumor microenvironment constitute a major obstacle in achieving
      robust CD8+ T cell antitumor immunotherapy. In the present study, we designed a
      photoimmunotherapy-based strategy involving a combination of photothermal and
      photodynamic therapies, followed by Treg cell suppression, for eliciting an
      immune response with IR-780- and imatinib-loaded layer-by-layer hybrid
      nanoparticles. Methods: The layer-by-layer hybrid nanoparticles were prepared
      through electrostatic interactions. Their photothermal effect, photodynamic
      effect as well as their effect on inhibiting Treg cells' suppressive function
      were investigated in vitro and in vivo. Their antitumor effect was evaluated
      using B16/BL6 and MC-38 tumor-bearing mice. Results: The layer-by-layer hybrid
      nanoparticles, which were pH-sensitive, enabled the release of IR-780 dye for NIR
      induced photothermal and photodynamic effects, and the release of imatinib-loaded
      glucocorticoid-induced TNF receptor family-related protein/poly(lactic-co
      glycolic acid) (GITR-PLGA) nanoparticles to initiate antitumor immunotherapy. The
      photothermal and photodynamic effects caused by IR-780 under NIR exposure
      resulted in direct tumor apoptosis/necrosis and the production of tumor
      associated antigen, promoted dendritic cell maturation, and enhanced the
      presentation of tumor-associated antigen to T cells, while the imatinib-loaded
      GITR-PLGA cores reduced the suppressive function of Treg cells, and consequently
      activated effective CD8+ T cells towards tumors. Conclusion: With the significant
      photothermal, photodynamic and immunotherapies, the system successfully
      eradicated tumor growth, diminished tumor recurrence, and improved survival in
      vivo. The proposed nanoparticles provide a novel and versatile approach to boost
      antitumor photoimmunotherapy.

PMID- 30279724
TI  - Radiopaque and uniform alginate microspheres loaded with tantalum nanoparticles
      for real-time imaging during transcatheter arterial embolization.
AB  - One restriction to the development and application of transcatheter arterial
      chemoembolization (TACE) therapy is the lack of an inherently radiopaque embolic
      whose location and distribution can be precisely visualized in real time and be
      used for non-invasive examination after surgery. Methods: A one-step electrospray
      method was developed to fabricate calcium alginate microspheres loaded with
      tantalum nanoparticles (Ta@CaAlg). The parameters of electrospraying were
      assessed. The in vivo X-ray imaging capability and embolic effect of Ta@CaAlg
      microspheres were evaluated in the renal arteries of normal rabbits by digital
      radiography and computed tomography. Doxorubicin hydrochloride (Dox) was chosen
      as a model drug, and the drug loading capacity and release behavior of these
      microspheres was valuated in vitro. Results: Spherical Ta@CaAlg microspheres with
      monodisperse sizes ranging from 150 to 1200 MUm were fabricated by
      electrospraying. The results of an in vivo study showed that Ta@CaAlg
      microspheres possessed the qualities of both embolic agents and contrast media.
      They could not only feed back the real-time location and distribution of the
      embolic microspheres but also maintained clear X-ray imaging of embolized sites
      for up to 4 weeks as assessed by digital radiography and computed tomography.
      Digital subtraction angiography showed that they had an excellent embolic effect.
      Ta@CaAlg microspheres could be loaded with Dox to form "3-in-1" embolic
      microspheres. The maximum Dox loading was 97.3 mg Dox per mL beads and loaded
      microspheres exhibited pH-dependent release profiles. Conclusion: The X-ray
      opacity and drug-loading capability of Ta@CaAlg microspheres offers great promise
      in direct, real-time, in vivo investigation for TACE and long-term non-invasive
      re-examination.

PMID- 30279725
TI  - Erratum: Early Assessment of Tumor Response to Radiation Therapy using High
      Resolution Quantitative Microvascular Ultrasound Imaging: Erratum.
AB  - [This corrects the article DOI: 10.7150/thno.19703.].

PMID- 30279726
TI  - ATP-activated decrosslinking and charge-reversal vectors for siRNA delivery and
      cancer therapy.
AB  - Stimuli-responsive polycations have been developed for improved nucleic acid
      transfection and enhanced therapeutic efficacy. The most reported mechanisms for
      controlled release of siRNA are based on polyelectrolyte exchange reactions in
      the cytoplasm and the degradation of polycations initiated by specific triggers.
      However, the degradation strategy has not always been sufficient due to
      unsatisfactory kinetics and binding of cationic fragments to siRNA, which limits
      the gene silencing effect. In this study, a new strategy that combines
      degradation and charge reversal is proposed. Methods: We prepared a polycation
      (CrossPPA) by crosslinking of phenylboronic acid (PBA)-grafted 1.8k PEI with
      alginate. It was compared with 25k PEI, 1.8k PEI and 1.8k PEI-PBA on siRNA
      encapsulation, ATP-responsive behavior and mechanism, cytotoxicity, cell uptake,
      siRNA transfection, in vivo biodistribution and in vivo anti-tumor efficacy. The
      in vitro and in vivo experiments were performed on 4T1 murine breast cancer cells
      and 4T1 tumor model separately. Results: The crosslinking strategy obviously
      improve the siRNA loading ability of 1.8k PEI. We validated that intracellular
      levels of ATP could trigger CrossPPA disassembly and charge reversal, which
      resulted in efficient and rapid siRNA release due to electrostatic repulsion.
      Besides, CrossPPA/siRNA showed strong cell uptake in 4T1 cells compared with 1.8k
      PEI/siRNA. Notably, the cytotoxicity of CrossPPA was pretty low, which was owing
      to its biodegradability. Furthermore, the crosslinked polyplexes significantly
      enhanced siRNA transfection and improved tumor accumulation. The high gene
      silencing ability of CrossPPA polyplex led to strong anti-tumor efficacy when
      using Bcl2-targeted siRNA. Conclusion: These results indicated that the ATP
      triggered disassembly and charge reversal strategy provided a new way for
      developing stimuli-responsive siRNA carriers and showed potential for nucleic
      acid delivery in the treatment of cancer.

PMID- 30279727
TI  - Senescent fibroblasts drive ageing pigmentation: A potential therapeutic target
      for senile lentigo.
AB  - Cutaneous ageing is an important extrinsic process that modifies the pigmentary
      system. Because cellular senescence is a fundamental ageing mechanism, we
      examined the role of senescent cells in ageing pigmentation. Methods: Biopsies
      obtained from senile lentigo and perilesional normal skin were assayed for a
      marker of cellular senescence, p16INK4A. To determine the secretory phenotypes of
      senescent fibroblasts, we performed microarray, RNA sequencing and methylation
      array analyses in senile lentigo and senescent fibroblasts. To further
      investigate the impact of senescent cells on ageing-related pigmentation, an
      intervention that targeted senescent cells using radiofrequency was performed.
      Results: In vivo, senescent fibroblasts accumulated at the sites of age-related
      pigmentation. Phenotype switching of the cells resulted in the repression of
      stromal-derived factor 1 (SDF1) by promoter methylation. SDF1 induced melanocyte
      differentiation via stromal-epithelial interactions, ultimately driving skin
      pigmentation. Furthermore, the elimination of senescent fibroblasts from
      pigmented skin using radiofrequency was accompanied by skin lightening, rendering
      it a potential target for treatment. Conclusion: Aged pigmented skin contains an
      increasing proportion of senescent fibroblasts. Cells with phenotype switching
      exhibited a loss of SDF1, which stimulates the melanogenic process and thereby
      contributes to aging pigmentation. These data may promote the development of new
      therapeutic paradigms, such as a stroma-targeting therapy for pigmentary
      disorders.

PMID- 30279728
TI  - Aphthous ulcer drug inhibits prostate tumor metastasis by targeting IKKE/TBK1/NF
      kappaB signaling.
AB  - Tumor metastasis is the major cause of death for prostate cancer (PCa) patients.
      However, the treatment options for metastatic PCa are very limited. Epithelial
      mesenchymal transition (EMT) has been reported to be an indispensable step for
      tumor metastasis and is suggested to associate with acquisition of cancer stem
      cell (CSC) attributes. We propose that small-molecule compounds that can reverse
      EMT or induce mesenchymal-epithelial transition (MET) of PCa cells may serve as
      drug candidates for anti-metastasis therapy. Methods: The promoters of CDH1 and
      VIM genes were sub-cloned to drive the expression of firefly and renilla
      luciferase reporter in a lentiviral vector. Mesenchymal-like PCa cells were
      infected with the luciferase reporter lentivirus and subjected to drug screening
      from a 1274 approved small-molecule drug library for the identification of agents
      to reverse EMT. The dosage-dependent effect of candidate compounds was confirmed
      by luciferase reporter assay and immunoblotting. Wound-healing assay, sphere
      formation, transwell migration assay, and in vivo intracardiac and orthotopic
      tumor xenograft experiments were used to evaluate the mobility, metastasis and
      tumor initiating capacity of PCa cells upon treatment. Possible downstream
      signaling pathways affected by the candidate compound treatment were analyzed by
      RNA sequencing and immunoblotting. Results: Drug screening identified Amlexanox,
      a drug used for recurrent aphthous ulcers, as a strong agent to reverse EMT.
      Amlexanox induced significant suppression of cell mobility, invasion, serial
      sphere formation and in vivo metastasis and tumor initiating capacity of PCa
      cells. Amlexanox treatment led to downregulation of the IKK-E/ TBK1/ NF-kappaB
      signaling pathway. The effect of Amlexanox on EMT reversion and cell mobility
      inhibition can be mimicked by other IKK-E/TBK1 inhibitors and rescued by
      reconstitution of dominant active NF-kappaB. Conclusions: Amlexanox can
      sufficiently suppress PCa metastasis by reversing EMT through downregulating the
      IKK-E/TBK1/NF-kappaB signaling axis.

PMID- 30279729
TI  - Hypoxia-induced up-regulation of VASP promotes invasiveness and metastasis of
      hepatocellular carcinoma.
AB  - Rational: Patients with hepatocellular carcinoma (HCC) have a poor prognosis
      mostly due to intrahepatic as well as distal metastasis. Vasodilator-stimulated
      phosphoprotein (VASP), a regulator of actin cytoskeleton and cell migration, is
      overexpressed in HCC and correlated with its malignant features and poor
      prognosis. Very little is known about its function in HCC. Methods: qRT-PCR,
      Western blot and IHC were used to detect the VASP expression in tissues and
      cells. Transwell and wound healing assays were used to measure the migration and
      invasion of HCC cells. Immunoblotting and immunofluorescence were used for
      detection of epithelial-to-mesenchymal transition (EMT) progression in HCC cells.
      A lung metastasis mouse model was used to evaluate metastasis of HCC in vivo. The
      putative targets of miR-204 were disclosed by public databases and a dual
      luciferase reporter assay. IP was used to show the interaction between VASP and
      CRKL. ChIP was used to analyze the binding of HIF-1alpha to VASP promoter region.
      Results: Our data involving both gain- and loss-of-function studies revealed that
      VASP activated AKT and ERK signaling and promoted HCC migration and invasion in
      vitro and in vivo by altering the EMT phenotype and expression of MMPs. We
      investigated the positive correlation between VASP and an adapter protein, CRKL.
      VASP dynamically co-localized at the SH3N domain of CRKL and mediated its
      function. Mechanistically, VASP overexpression at the transcriptional level was
      mediated by HIF-1alpha through direct binding to two hypoxia response elements
      (HRE) in the VASP promoter region. Furthermore, we identified hypoxia-induced
      down-regulation of miR-204, which functioned as the regulator of VASP
      overexpression at the post-transcriptional level. Also, hypoxia-activated p-Smad3
      dependent TGF-beta signaling indirectly promoted VASP expression. Conclusion: A
      variety of hypoxia-induced molecular mechanisms contributed to the upregulation
      of VASP at transcriptional and post-transcriptional levels. These mechanisms
      involved CRKL, HIF-1alpha, miR-204, and TGF-beta activating the AKT and ERK
      signaling to promote EMT and expression of MMPs. Taken together, our results
      defined VASP as an oncogene of HCC pathogenesis and metastasis with the potential
      to serve as a prognostic biomarker.

PMID- 30279730
TI  - Pepducin-mediated cardioprotection via beta-arrestin-biased beta2-adrenergic
      receptor-specific signaling.
AB  - Reperfusion as a therapeutic intervention for acute myocardial infarction-induced
      cardiac injury itself induces further cardiomyocyte death. beta-arrestin
      (betaarr)-biased beta-adrenergic receptor (betaAR) activation promotes survival
      signaling responses in vitro; thus, we hypothesize that this pathway can mitigate
      cardiomyocyte death at the time of reperfusion to better preserve function.
      However, a lack of efficacious betaarr-biased orthosteric small molecules has
      prevented investigation into whether this pathway relays protection against
      ischemic injury in vivo. We recently demonstrated that the pepducin ICL1-9, a
      small lipidated peptide fragment designed from the first intracellular loop of
      beta2AR, allosterically engaged pro-survival signaling cascades in a betaarr
      dependent manner in vitro. Thus, in this study we tested whether ICL1-9 relays
      cardioprotection against ischemia/reperfusion (I/R)-induced injury in vivo.
      Methods: Wild-type (WT) C57BL/6, beta2AR knockout (KO), betaarr1KO and betaarr2KO
      mice received intracardiac injections of either ICL1-9 or a scrambled control
      pepducin (Scr) at the time of ischemia (30 min) followed by reperfusion for
      either 24 h, to assess infarct size and cardiomyocyte death, or 4 weeks, to
      monitor the impact of ICL1-9 on long-term cardiac structure and function.
      Neonatal rat ventricular myocytes (NRVM) were used to assess the impact of ICL1-9
      versus Scr pepducin on cardiomyocyte survival and mitochondrial superoxide
      formation in response to either serum deprivation or hypoxia/reoxygenation (H/R)
      in vitro and to investigate the associated mechanism(s). Results: Intramyocardial
      injection of ICL1-9 at the time of I/R reduced infarct size, cardiomyocyte death
      and improved cardiac function in a beta2AR- and betaarr-dependent manner, which
      led to improved contractile function early and less fibrotic remodeling over
      time. Mechanistically, ICL1-9 attenuated mitochondrial superoxide production and
      promoted cardiomyocyte survival in a RhoA/ROCK-dependent manner. RhoA activation
      could be detected in cardiomyocytes and whole heart up to 24 h post-treatment,
      demonstrating the stability of ICL1-9 effects on betaarr-dependent beta2AR
      signaling. Conclusion: Pepducin-based allosteric modulation of betaarr-dependent
      beta2AR signaling represents a novel therapeutic approach to reduce reperfusion
      induced cardiac injury and relay long-term cardiac remodeling benefits.

PMID- 30279731
TI  - Dopaminergic precursors differentiated from human blood-derived induced neural
      stem cells improve symptoms of a mouse Parkinson's disease model.
AB  - Autologous neural stem cells (NSCs) may offer a promising source for deriving
      dopaminergic (DA) cells for treatment of Parkinson's disease (PD). Methods: By
      using Sendai virus, human peripheral blood mononuclear cells (PBMNCs) were
      reprogrammed to induced NSCs (iNSCs), which were then differentiated to
      dopaminergic neurons in vitro. Whole-genome deep sequencing was performed to
      search for mutations that had accumulated during the reprogramming and expansion
      processes. To find the optimal differentiation stage of cells for
      transplantation, DA precursors obtained at various differentiation time points
      were tested by engraftment into brains of naive immunodeficient mice. At last,
      the safety and efficacy of iNSC-derived DA precursors were tested by
      transplantation into the striatum of immunodeficient PD mouse models. Results:
      PBMNC-derived iNSCs showed similar characteristics to fetal NSCs, and were able
      to specifically differentiate to DA neurons with high efficiency in vitro. The
      sequencing data proved that no harmful SNVs, Indels and CNVs were generated
      during the reprogramming and expansion processes. DA precursors obtained between
      differentiation day 10 to 13 in vitro were most suitable for transplantation when
      a balanced graft survival and maturation were taken into account. Two weeks after
      transplantation of DA precursors into mouse PD models, the motor functions of PD
      mice started to improve, and continued to improve until the end of the
      experiments. No graft overgrowth or tumor was observed, and a significant number
      of A9-specific midbrain DA neurons were surviving in the striatum. Conclusion:
      This study confirmed the efficacy of iNSC-derived DA precursors in a mouse PD
      model, and emphasized the necessity of genomic sequencing and vigorous safety
      assessment before any clinical translation using iNSCs.

PMID- 30279732
TI  - Galphai1 and Galphai3mediate VEGF-induced VEGFR2 endocytosis, signaling and
      angiogenesis.
AB  - VEGF binding to VEGFR2 leads to VEGFR2 endocytosis and downstream signaling
      activation to promote angiogenesis. Methods: Using genetic strategies, we tested
      the requirement of alpha subunits of heterotrimeric G proteins (Galphai1/3) in
      the process. Results: Galphai1/3 are located in the VEGFR2 endocytosis complex
      (VEGFR2-Ephrin-B2-Dab2-PAR-3), where they are required for VEGFR2 endocytosis and
      downstream signaling transduction. Galphai1/3 knockdown, knockout or dominant
      negative mutation inhibited VEGF-induced VEGFR2 endocytosis, and downstream Akt
      mTOR and Erk-MAPK activation. Functional studies show that Galphai1/3 shRNA
      inhibited VEGF-induced proliferation, invasion, migration and vessel-like tube
      formation of HUVECs. In vivo, Galphai1/3 shRNA lentivirus inhibited alkali burn
      induced neovascularization in mouse cornea. Further, oxygen-induced retinopathy
      (OIR)-induced retinal neovascularization was inhibited by intravitreal injection
      of Galphai1/3 shRNA lentivirus. Moreover, in vivo angiogenesis by alkali burn and
      OIR was significantly attenuated in Galphai1/3 double knockout mice.
      Significantly, Galphai1/3 proteins are upregulated in proliferative retinal
      tissues of proliferative diabetic retinopathy (PDR) patients. Conclusion: These
      results provide mechanistic insights into the critical role played by Galphai1/3
      proteins in VEGF-induced VEGFR2 endocytosis, signaling and angiogenesis.

PMID- 30279733
TI  - Nanoparticles for diagnosis and therapy of atherosclerosis and myocardial
      infarction: evolution toward prospective theranostic approaches.
AB  - Cardiovascular diseases are the leading cause of death worldwide. Despite
      preventive efforts, early detection of atherosclerosis, the common
      pathophysiological mechanism underlying cardiovascular diseases remains elusive,
      and overt coronary artery disease or myocardial infarction is often the first
      clinical manifestation. Nanoparticles represent a novel strategy for prevention,
      diagnosis, and treatment of atherosclerosis, and new multifunctional
      nanoparticles with combined diagnostic and therapeutic capacities hold the
      promise for theranostic approaches to this disease. This review focuses on the
      development of nanosystems for therapy and diagnosis of subclinical
      atherosclerosis, coronary artery disease, and myocardial infarction and the
      evolution of nanosystems as theranostic tools. We also discuss the use of
      nanoparticles in noninvasive imaging, targeted drug delivery, photothermal
      therapies together with the challenges faced by nanosystems during clinical
      translation.

PMID- 30279734
TI  - Mesenchymal glioblastoma constitutes a major ceRNA signature in the TGF-beta
      pathway.
AB  - Rationale: Competitive endogenous RNA (ceRNA) networks play important roles in
      posttranscriptional regulation. Their dysregulation is common in cancer. However,
      ceRNA signatures have been poorly examined in the invasive and aggressive
      phenotypes of mesenchymal glioblastoma (GBM). This study aims to characterize
      mesenchymal glioblastoma at the mRNA-miRNA level and identify the mRNAs in ceRNA
      networks (micNET) markers and their mechanisms in tumorigenesis. Methods: The
      mRNAs in ceRNA networks (micNETs) of glioblastoma were investigated by
      constructing a GBM ceRNA network followed by integration with a STRING protein
      interaction network. The prognostic micNET markers of mesenchymal GBM were
      identified and validated across multiple datasets. ceRNA interactions were
      identified between micNETs and miR181 family members. LY2109761, an inhibitor of
      TGFBR2, demonstrated tumor-suppressive effects on both primary cultured cells and
      a patient-derived xenograft intracranial model. Results: We characterized
      mesenchymal glioblastoma at the mRNA-miRNA level and reported a ceRNA network
      that could separate the mesenchymal subtype from other subtypes. Six genes
      (TGFBR2, RUNX1, PPARG, ACSL1, GIT2 and RAP1B) that interacted with each other in
      both a ceRNA-related manner and in terms of their protein functions were
      identified as markers of the mesenchymal subtype. The coding sequence (CDS) and
      3'-untranslated region (UTR) of TGFBR2 upregulated the expression of these genes,
      whereas TGFBR2 inhibition by siRNA or miR-181a/d suppressed their expression
      levels. Furthermore, mesenchymal subtype-related genes and the invasion phenotype
      could be reversed by suppressing the six mesenchymal marker genes. Conclusions:
      This study suggests that the micNETs may have translational significance in the
      diagnosis of mesenchymal GBM and may be novel therapeutic targets.

PMID- 30279735
TI  - Optogenetic sensors in the zebrafish heart: a novel in vivo electrophysiological
      tool to study cardiac arrhythmogenesis.
AB  - Cardiac arrhythmias are among the most challenging human disorders to diagnose
      and treat due to their complex underlying pathophysiology. Suitable experimental
      animal models are needed to study the mechanisms causative for cardiac
      arrhythmogenesis. To enable in vivo analysis of cardiac cellular
      electrophysiology with a high spatial and temporal resolution, we generated and
      carefully validated two zebrafish models, one expressing an optogenetic voltage
      indicator (chimeric VSFP-butterfly CY) and the other a genetically encoded
      calcium indicator (GCaMP6f) in the heart. Methods: High-speed epifluorescence
      microscopy was used to image chimeric VSFP-butterfly CY and GCaMP6f in the
      embryonic zebrafish heart, providing information about the spatiotemporal
      patterning of electrical activation, action potential configuration and
      intracellular Ca2+ dynamics. Plotting VSFP or GCaMP6f signals on a line along the
      myocardial wall over time facilitated the visualization and analysis of
      electrical impulse propagation throughout the heart. Administration of drugs
      targeting the sympathetic nervous system or cardiac ion channels was used to
      validate sensitivity and kinetics of both zebrafish sensor lines. Using the same
      microscope setup, we imaged transparent juvenile casper fish expressing GCaMP6f,
      demonstrating the feasibility of imaging cardiac optogenetic sensors at later
      stages of development. Results: Isoproterenol slightly increased heart rate,
      diastolic Ca2+ levels and Ca2+ transient amplitudes, whereas propranolol caused a
      profound decrease in heart rate and Ca2+ transient parameters in VSFP-Butterfly
      and GCaMP6f embryonic fish. Ikr blocker E-4031 decreased heart rate and increased
      action potential duration in VSFP-Butterfly fish. ICa,L blocker nifedipine caused
      total blockade of Ca2+ transients in GCaMP6f fish and a reduced heart rate,
      altered ventricular action potential duration and disrupted atrial-ventricular
      electrical conduction in VSFP-Butterfly fish. Imaging of juvenile animals
      demonstrated the possibility of employing an older zebrafish model for in vivo
      cardiac electrophysiology studies. We observed differences in atrial and
      ventricular Ca2+ recovery dynamics between 3 dpf and 14 dpf casper fish, but not
      in Ca2+ upstroke dynamics. Conclusion: By introducing the optogenetic sensors
      chimeric VSFP-butterfly CY and GCaMP6f into the zebrafish we successfully
      generated an in vivo cellular electrophysiological readout tool for the zebrafish
      heart. Complementary use of both sensor lines demonstrated the ability to study
      heart rate, cardiac action potential configuration, spatiotemporal patterning of
      electrical activation and intracellular Ca2+ homeostasis in embryonic zebrafish.
      In addition, we demonstrated the first successful use of an optogenetic sensor to
      study cardiac function in older zebrafish. These models present a promising new
      research tool to study the underlying mechanisms of cardiac arrhythmogenesis.

PMID- 30279736
TI  - Simultaneous characterization of tumor cellularity and the Warburg effect with
      PET, MRI and hyperpolarized 13C-MRSI.
AB  - Modern oncology aims at patient-specific therapy approaches, which triggered the
      development of biomedical imaging techniques to synergistically address tumor
      biology at the cellular and molecular level. PET/MR is a new hybrid modality that
      allows acquisition of high-resolution anatomic images and quantification of
      functional and metabolic information at the same time. Key steps of the Warburg
      effect-one of the hallmarks of tumors-can be measured non-invasively with this
      emerging technique. The aim of this study was to quantify and compare
      simultaneously imaged augmented glucose uptake and LDH activity in a subcutaneous
      breast cancer model in rats (MAT-B-III) and to study the effect of varying tumor
      cellularity on image-derived metabolic information. Methods: For this purpose, we
      established and validated a multimodal imaging workflow for a clinical PET/MR
      system including proton magnetic resonance (MR) imaging to acquire accurate
      morphologic information and diffusion-weighted imaging (DWI) to address tumor
      cellularity. Metabolic data were measured with dynamic [18F]FDG-PET and
      hyperpolarized (HP) 13C-pyruvate MR spectroscopic imaging (MRSI). We applied our
      workflow in a longitudinal study and analyzed the effect of growth dependent
      variations of cellular density on glycolytic parameters. Results: Tumors of
      similar cellularity with similar apparent diffusion coefficients (ADC) showed a
      significant positive correlation of FDG uptake and pyruvate-to-lactate exchange.
      Longitudinal DWI data indicated a decreasing tumor cellularity with tumor growth,
      while ADCs exhibited a significant inverse correlation with PET standard uptake
      values (SUV). Similar but not significant trends were observed with HP-13C-MRSI,
      but we found that partial volume effects and point spread function artifacts are
      major confounders for the quantification of 13C-data when the spatial resolution
      is limited and major blood vessels are close to the tumor. Nevertheless, analysis
      of longitudinal data with varying tumor cellularity further detected a positive
      correlation between quantitative PET and 13C-data. Conclusions: Our workflow
      allows the quantification of simultaneously acquired PET, MRSI and DWI data in
      rodents on a clinical PET/MR scanner. The correlations and findings suggest that
      a major portion of consumed glucose is metabolized by aerobic glycolysis in the
      investigated tumor model. Furthermore, we conclude that variations in cell
      density affect PET and 13C-data in a similar manner and correlations of
      longitudinal metabolic data appear to reflect both biochemical processes and
      tumor cellularity.

PMID- 30279737
TI  - RGS4 deficit in prefrontal cortex contributes to the behaviors related to
      schizophrenia via system xc --mediated glutamatergic dysfunction in mice.
AB  - Rationale: Although molecular investigations of regulator of G-protein signaling
      4 (RGS4) alterations in schizophrenia patients yielded partially inconsistent
      findings, the previous studies suggested that RGS4 is both a positional and
      functional candidate gene for schizophrenia and is significantly decreased in the
      prefrontal cortex. However, the exact role of RGS4 in the pathophysiology of
      schizophrenia is unclear. Moreover, a whole genome transcription profile study
      showed the possibility of RGS4-regulated expression of SLC7A11(xCT), a component
      of cysteine/glutamate transporter or system xc -. We hypothesized that system xc 
      is a therapeutic target of RGS4 deficit-mediated schizophrenia. Methods:
      Pharmacological and genetic manipulation of RGS4 in organotypic brain slice
      cultures were used as an ex vivo model to investigate its role in system xc - and
      glutamatergic function. Lentiviral-based mouse models with RGS4 deficit in the
      prefrontal cortex and treatment with system xc - activator, N-acetyl cysteine
      (NAC), were utilized to observe their impacts on glutamatergic function and
      schizophrenic behaviors. Results: Genetic and pharmacological inhibition of RGS4
      resulted in a significant decrease in SLC7A11 (xCT) expression and hypofunction
      of system xc - and reduced glutamatergic function in organotypic brain slice
      cultures. However, NAC restored the dysregulation of RGS4-mediated functional
      deficits of glutamate. Moreover, knockdown of RGS4 specifically in the prefrontal
      cortex caused mice to exhibit behaviors related to schizophrenia such as
      increased stereotypy, impaired prepulse inhibition, deficits in social
      interactions, working memory, and nesting behavior, while enhancing sensitivity
      to the locomotor stimulatory effect of MK-801. These mice displayed glutamatergic
      dysfunction in the prefrontal cortex, which may have contributed to the
      behavioral deficits. RGS4 knockdown mice that received NAC treatment had improved
      glutamatergic dysfunction and schizophrenia behaviors. Conclusion: Our results
      suggest that RGS4 deficit induces dysregulation and dysfunction of system xc -,
      which further results in functional deficits of the glutamatergic system and
      subsequently to schizophrenia-related behavioral phenotypes. Activation of system
      xc - offers a promising strategy to treat RGS4 deficit-mediated schizophrenia.

PMID- 30279738
TI  - Inhibition of Notch1 induces population and suppressive activity of regulatory T
      cell in inflammatory arthritis.
AB  - Inhibition of Notch signalling has shown anti-inflammatory properties in vivo and
      in vitro models of rheumatoid arthritis (RA). The objective of this study was to
      determine whether Notch1 might play a role in regulating T-regulatory cells
      (Tregs) in animal models of RA. Methods: Collagen-induced arthritis (CIA) and
      collagen antibody-induced arthritis (CAIA) were induced in C57BL/6, Notch1
      antisense transgenic (NAS) or DBA1/J mice. We examined whether pharmacological
      inhibitors of gamma-secretase (an enzyme required for Notch1 activation) and
      antisense-mediated knockdown of Notch1 could attenuate the severity of
      inflammatory arthritis in CIA and CAIA mice. Proportions of CD4+CD25+Foxp3+ Treg
      cells were measured by flow cytometry. To assess the suppressive capacity of Treg
      toward responder cells, CFSE-based suppression assay of Treg was performed.
      Results: gamma-secretase inhibitors and antisense-mediated knockdown of Notch1
      reduced the severity of inflammatory arthritis in both CIA and CAIA mice.
      Pharmacological and genetic inhibition of Notch1 signalling induced significant
      elevation of Treg cell population in CIA and CAIA mice. We also demonstrated that
      inhibition of Notch signalling suppressed the progression of inflammatory
      arthritis through modulating the expansion and suppressive function of regulatory
      T (Treg) cells. Conclusion: Pharmacological and genetic inhibition of Notch1
      signalling suppresses the progression of inflammatory arthritis through
      modulating the population and suppressive function of Treg cells in animal models
      of RA.

PMID- 30279739
TI  - WNT6 is a novel oncogenic prognostic biomarker in human glioblastoma.
AB  - Glioblastoma (GBM) is a universally fatal brain cancer, for which novel therapies
      targeting specific underlying oncogenic events are urgently needed. While the WNT
      pathway has been shown to be frequently activated in GBM, constituting a
      potential therapeutic target, the relevance of WNT6, an activator of this
      pathway, remains unknown. Methods: WNT6 protein and mRNA levels were evaluated in
      GBM. WNT6 levels were silenced or overexpressed in GBM cells to assess functional
      effects in vitro and in vivo. Phospho-kinase arrays and TCF/LEF reporter assays
      were used to identify WNT6-signaling pathways, and significant associations with
      stem cell features and cancer-related pathways were validated in patients.
      Survival analyses were performed with Cox regression and Log-rank tests. Meta
      analyses were used to calculate the estimated pooled effect. Results: We show
      that WNT6 is significantly overexpressed in GBMs, as compared to lower-grade
      gliomas and normal brain, at mRNA and protein levels. Functionally, WNT6
      increases typical oncogenic activities in GBM cells, including viability,
      proliferation, glioma stem cell capacity, invasion, migration, and resistance to
      temozolomide chemotherapy. Concordantly, in in vivo orthotopic GBM mice models,
      using both overexpressing and silencing models, WNT6 expression was associated
      with shorter overall survival, and increased features of tumor aggressiveness.
      Mechanistically, WNT6 contributes to activate typical oncogenic pathways,
      including Src and STAT, which intertwined with the WNT pathway may be critical
      effectors of WNT6-associated aggressiveness in GBM. Clinically, we establish WNT6
      as an independent prognostic biomarker of shorter survival in GBM patients from
      several independent cohorts. Conclusion: Our findings establish WNT6 as a novel
      oncogene in GBM, opening opportunities to develop more rational therapies to
      treat this highly aggressive tumor.

PMID- 30279740
TI  - Neurogliovascular dysfunction in a model of repeated traumatic brain injury.
AB  - Traumatic brain injury (TBI) research has focused on moderate to severe injuries
      as their outcomes are significantly worse than those of a mild TBI (mTBI).
      However, recent epidemiological evidence has indicated that a series of even mild
      TBIs greatly increases the risk of neurodegenerative and psychiatric disorders.
      Neuropathological studies of repeated TBI have identified changes in neuronal
      ionic concentrations, axonal injury, and cytoskeletal damage as important
      determinants of later life neurological and mood compromise; yet, there is a
      paucity of data on the contribution of neurogliovascular dysfunction to the
      progression of repeated TBI and alterations of brain function in the intervening
      period. Methods: Here, we established a mouse model of repeated TBI induced via
      three electromagnetically actuated impacts delivered to the intact skull at three
      day intervals and determined the long-term deficits in neurogliovascular
      functioning in Thy1-ChR2 mice. Two weeks post the third impact, cerebral blood
      flow and cerebrovascular reactivity were measured with arterial spin labelling
      magnetic resonance imaging. Neuronal function was investigated through bilateral
      intracranial electrophysiological responses to optogenetic photostimulation.
      Vascular density of the site of impacts was measured with in vivo two photon
      fluorescence microscopy. Pathological analysis of neuronal survival and
      astrogliosis was performed via NeuN and GFAP immunofluorescence. Results:
      Cerebral blood flow and cerebrovascular reactivity were decreased by 50+/-16% and
      70+/-20%, respectively, in the TBI cohort relative to sham-treated animals.
      Concomitantly, electrophysiological recordings revealed a 97+/-1% attenuation in
      peri-contusional neuronal reactivity relative to sham. Peri-contusional vascular
      volume was increased by 33+/-2% relative to sham-treated mice. Pathological
      analysis of the peri-contusional cortex demonstrated astrogliosis, but no changes
      in neuronal survival. Conclusion: This work provides the first in-situ
      characterization of the long-term deficits of the neurogliovascular unit
      following repeated TBI. The findings will help guide the development of
      diagnostic markers as well as therapeutics targeting neurogliovascular
      dysfunction.

PMID- 30279742
TI  - Evaluation of antibody fragment properties for near-infrared fluorescence imaging
      of HER3-positive cancer xenografts.
AB  - In vivo imaging is influenced by the half-life, tissue penetration,
      biodistribution, and affinity of the imaging probe. Immunoglobulin G (IgG) is
      composed of discrete domains with known functions, providing a template for
      engineering antibody fragments with desired imaging properties. Here, we
      engineered antibody-based imaging probes, consisting of different combinations of
      antibody domains, labeled them with the near-infrared fluorescent dye IRDye800CW,
      and evaluated their in vivo imaging properties. Antibody-based imaging probes
      were based on an anti-HER3 antigen binding fragment (Fab) isolated using phage
      display. Methods: We constructed six anti-HER3 antibody-based imaging probes: a
      single chain variable fragment (scFv), Fab, diabody, scFv-CH3, scFv-Fc, and IgG.
      IRDye800CW-labeled, antibody-based probes were injected into nude mice bearing
      FaDu xenografts and their distribution to the xenograft, liver, and kidneys was
      evaluated. Results: These imaging probes bound to recombinant HER3 and to the
      HER3-positive cell line, FaDu. Small antibody fragments with molecular weight <60
      kDa (scFv, diabody, and Fab) accumulated rapidly in the xenograft (maximum
      accumulation between 2-4 h post injection (hpi)) and cleared primarily through
      the kidneys. scFv-CH3 (80 kDa) had fast clearance and peaked in the xenograft
      between 2-3 hpi and cleared from xenograft in a rate comparable to Fab and
      diabody. IgG and scFv-Fc persisted in the xenografts for up to 72 hpi and
      distributed mainly to the xenograft and liver. The highest xenograft fluorescence
      signals were observed with IgG and scFv-Fc imaging probes and persisted for 2-3
      days. Conclusion: These results highlight the utility of using antibody fragments
      to optimize clearance, tumor labeling, and biodistribution properties for
      developing anti-HER3 probes for image-guided surgery or PET imaging.

PMID- 30279741
TI  - MRI and histological evaluation of pulsed focused ultrasound and microbubbles
      treatment effects in the brain.
AB  - Magnetic resonance imaging (MRI)-guided pulsed focused ultrasound (pFUS) combined
      with microbubbles (MB) contrast agent infusion has been shown to transiently
      disrupt the blood-brain barrier (BBBD), increasing the delivery of
      neurotherapeutics to treat central nervous system (CNS) diseases. pFUS
      interaction with the intravascular MB results in acoustic cavitation forces
      passing through the neurovascular unit (NVU), inducing BBBD detected on contrast
      enhanced MRI. Multiple pFUS+MB exposures in Alzheimer's disease (AD) models are
      being investigated as a method to clear amyloid plaques by activated microglia or
      infiltrating immune cells. Since it has been reported that pFUS+MB can induce a
      sterile inflammatory response (SIR) [1-5] in the rat, the goal of this study was
      to investigate the potential long-term effects of SIR in the brain following
      single and six weekly sonications by serial high-resolution MRI and pathology.
      Methods: Female Sprague Dawley rats weighing 217+/-16.6 g prior to sonication
      received bromo-deoxyuridine (BrdU) to tag proliferating cells in the brain. pFUS
      was performed at 548 kHz, ultrasound burst 10 ms and initial peak negative
      pressure of 0.3 MPa (in water) for 120 s coupled with a slow infusion of ~460
      uL/kg (5-8*107 MB) that started 30 s before and 30 s during sonication. Nine 2 mm
      focal regions in the left cortex and four regions over the right hippocampus were
      treated with pFUS+MB. Serial high-resolution brain MRIs at 3 T and 9.4 T were
      obtained following a single or during the course of six weekly pFUS+MB resulting
      in BBBD in the left cortex and the right hippocampus. Animals were monitored over
      7 to 13 weeks and imaging results were compared to histology. Results: Fewer than
      half of the rats receiving a single pFUS+MB exposure displayed hypointense voxels
      on T2*-weighted (w) MRI at week 7 or 13 in the cortex or hippocampus without
      differences compared to the contralateral side on histograms of T2* maps. Single
      sonicated rats had evidence of limited microglia activation on pathology compared
      to the contralateral hemisphere. Six weekly pFUS+MB treatments resulted in
      pathological changes on T2*w images with multiple hypointense regions, cortical
      atrophy, along with 50% of rats having persistent BBBD and astrogliosis by MRI.
      Pathologic analysis of the multiple sonicated animals demonstrated the presence
      of metallophagocytic Prussian blue-positive cells in the parenchyma with
      significantly (p<0.05) increased areas of activated astrocytes and microglia, and
      high numbers of systemic infiltrating CD68+ macrophages along with BrdU+ cells
      compared to contralateral brain. In addition, multiple treatments caused an
      increase in the number of hyperphosphorylated Tau (pTau)-positive neurons
      containing neurofibrillary tangles (NFT) in the sonicated cortex but not in the
      hippocampus when compared to contralateral brain, which was confirmed by Western
      blot (WB) (p<0.04). Conclusions: The repeated SIR following multiple pFUS+MB
      treatments could contribute to changes on MR imaging including persistent BBBD,
      cortical atrophy, and hypointense voxels on T2w and T2*w images consistent with
      pathological injury. Moreover, areas of astrogliosis, activated microglia, along
      with higher numbers of CD68+ infiltrating macrophages and BrdU+ cells were
      detected in multiple sonicated areas of the cortex and hippocampus. Elevations in
      pTau and NFT were detected in neurons of the multiple sonicated cortex. Minimal
      changes on MRI and histology were observed in single pFUS+MB-treated rats at 7
      and 13 weeks post sonication. In comparison, animals that received 6 weekly
      sonications demonstrated evidence on MRI and histology of vascular damage,
      inflammation and neurodegeneration associated with the NVU commonly observed in
      trauma. Further investigation is recommended of the long-term effects of multiple
      pFUS+MB in clinical trials.

PMID- 30279744
TI  - A case of reverse takotsubo cardiomyopathy caused by an eating disorder.
AB  - Takotsubo cardiomyopathy is an acquired transient cardiomyopathy that causes
      severe systolic dysfunction in the absence of coronary disease. Here we present a
      case of reverse takotsubo cardiomyopathy. A 67-year-old female was admitted for
      weakness and falls due to severe malnutrition. During her stay she was diagnosed
      with an eating disorder. She also developed chest pain during her hospitalization
      and was taken urgently for catheterization which showed normal coronary arteries
      with akinetic basal and inferior walls and hyperkinesis of the apex. Her ejection
      fraction decreased to 25% from 60% five days previously. She was diagnosed with
      reverse takotsubo. She was placed on an appropriate heart failure regimen and
      eventually transferred to inpatient rehabilitation. In its typical form,
      takotsubo causes apical ballooning due to hyperkinetic basal and inferior wall
      motion and apical hypokinesis. Reverse takotsubo causes a depressed basal segment
      with apical hyperkinesis usually brought on by severe emotional or physical
      stress. Our case is the first documented report of an eating disorder causing the
      reverse type of takotsubo cardiomyopathy. <Learning objective: The reader will be
      able to recognize stress-induced cardiomyopathy in the right clinical setting and
      understand that there are different variants of this condition that can present
      with multiple different wall motion abnormalities.>.

PMID- 30279745
TI  - Interesting electrophysiological findings in a patient with coexistence of atrial
      tachycardia originating from coronary sinus and slow-fast atrioventricular nodal
      reentrant tachycardia.
AB  - Slow-fast atrioventricular nodal tachycardia (AVNRT) has various
      electrophysiological aspects due to atrioventricular (AV) nodal physiology. In
      addition, concomitantly another form of arrhythmia with AVNRT, especially atrial
      tachycardia (AT), was an infrequent arrhythmia. A 38-year-old female with narrow
      QRS tachycardia underwent electrophysiological study due to frequent faintness.
      The electrophysiological study disclosed the coexistence of AT originating from
      coronary sinus (CS) with slow-fast AVNRT. We easily diagnosed AT originating from
      CS and terminated with several radiofrequency ablations (RFA) around CS. The
      diagnosis of slow-fast AVNRT, however, was somewhat difficult due to the
      following findings: (1) small amount of adenosine triphosphate (ATP) could
      terminate slow-fast AVNRT reproducibly; (2) we could provoke slow-fast AVNRT only
      by RV pacing with isoproterenol infusion. With other electrophysiological
      findings, we diagnosed slow-fast AVNRT. Radiofrequency energy was delivered
      initially in the posteroseptal region, followed by inside CS, and finally in the
      middle septal region, which completed the slow pathway ablation. After the
      procedure, we could never provoke these arrhythmias. <Learning objective:
      Coexistence of focal AT originating from CS with slow-fast AVNRT is a rare
      phenomenon. Furthermore, slow-fast AVNRT could show unusual characteristic as
      following: (1) small amount of ATP terminates slow-fast AVNRT; (2) atrial pacing
      never provoked slow-fast AVNRT with isoproterenol infusion whereas ventricular
      pacing did, which depends on the physiological characteristic of the dual AV
      nodal pathway. Accordingly, we should precisely assess the obtained
      electrophysiological findings.>.

PMID- 30279746
TI  - Simultaneous occurrence of spontaneous coronary artery dissections of the left
      anterior descending and right coronary arteries in acute myocardial infarction.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare and often fatal cause of
      ischemic heart disease that occurs predominantly in young or middle-aged patients
      who are otherwise healthy. Therefore, the accurate diagnosis of SCAD and
      initiation of appropriate treatment may be life-saving. Although recent case
      reports have described patients with SCAD who exhibited multiple coronary
      dissections in addition to the culprit lesion, the authors could not determine
      whether the multiple dissections occurred simultaneously or at different times.
      In this report, we describe a case involving the simultaneous occurrence of
      multiple SCADs in the right coronary artery and left anterior descending artery.
      Intravascular ultrasound helped us to confirm the diagnosis of multiple SCADs,
      confirm their simultaneous occurrence, and navigate the guidewire into the true
      lumen. <Learning objective: In general, spontaneous coronary artery dissection
      (SCAD) is a single-vessel disease; the left anterior descending artery is the
      vessel most often involved, followed by the right coronary artery. However, the
      possibility of other coronary dissections distant from the culprit lesion should
      be considered in patients who present with an acute coronary syndrome due to
      SCAD. A prompt diagnosis and patient-tailored management can reduce morbidity and
      mortality in this population.>.

PMID- 30279747
TI  - Unilateral recurrent nerve palsy and cardiovascular disease - Ortner's syndrome.
AB  - Recurrent laryngeal palsies are relatively common. Frequently, surgical
      procedures precede paresis. In rare cases a compression of the recurrent
      laryngeal nerve can be caused by enlarged cardiovascular structures. The
      phenomenon of compression of the left recurrent laryngeal nerve is explicitly
      designated as Ortner's syndrome, first described in 1897 by Norbert Ortner.
      Nowadays the compression of the right recurrent laryngeal nerve by cardiovascular
      structures is also associated with Ortner's syndrome. We report two cases of an
      82- and a 71-year-old patient who presented with hoarseness and each right- and
      left-sided vocal cord paralysis for further diagnosis. The ear, nose, and throat
      (ENT) examinations revealed no clarifying findings besides the vocal cord palsy,
      so extensive imaging techniques were used. The cause of left-sided recurrent
      laryngeal nerve palsy was a penetrated aortic ulcer caused by large thrombosed
      aneurysm of the aortic arch. The right-sided paresis arose due to aneurysmal
      enlargement of the brachiocephalic trunk and an aneurysm of right subclavian
      artery. These cases demonstrate that interdisciplinary medical work is important.
      The internal medical presentation of a patient with hoarseness without ENT
      medical findings should be considered. <Learning objective: Ortner's syndrome is
      described as the compression of the recurrent laryngeal nerve of pathologically
      enlarged cardiac structures such as left atrium in mitral stenosis, aortic
      aneurysm, and others. It is a rare cause of vocal cord paralysis and thus
      hoarseness but should be considered as a differential diagnosis, particularly if
      the patient has a cardiac history.>.

PMID- 30279749
TI  - Unmasking the culprit: MAPCA masquerading as RV failure in post surgical
      correction of TOF.
AB  - Pulmonary regurgitation and right ventricular dilatation are major determinants
      of long-term follow up of surgically corrected tetralogy of Fallot. Occasionally,
      there are undiagnosed associated anomalies, which can exaggerate pulmonary
      regurgitation. The present report describes long-term effect of major aorto
      pulmonary collateral on right ventricular volume also a result of successful
      intervention. <Learning objective: Following pulmonary valvotomy in conotruncal
      anomalies there is development of significant pulmonary regurgitation. On long
      term follow up, they are candidates for pulmonary valve replacement. A thorough
      search and management of associated defects (such as major aorto pulmonary
      collaterals, peripheral pulmonary stenosis) can reverse right ventricular
      dilatation and postpone pulmonary valve placement.>.

PMID- 30279743
TI  - Biomarker of food intake for assessing the consumption of dairy and egg products.
AB  - Dairy and egg products constitute an important part of Western diets as they
      represent an excellent source of high-quality proteins, vitamins, minerals and
      fats. Dairy and egg products are highly diverse and their associations with a
      range of nutritional and health outcomes are therefore heterogeneous. Such
      associations are also often weak or debated due to the difficulty in establishing
      correct assessments of dietary intake. Therefore, in order to better characterize
      associations between the consumption of these foods and health outcomes, it is
      important to identify reliable biomarkers of their intake. Biomarkers of food
      intake (BFIs) provide an accurate measure of intake, which is independent of the
      memory and sincerity of the subjects as well as of their knowledge about the
      consumed foods. We have, therefore, conducted a systematic search of the
      scientific literature to evaluate the current status of potential BFIs for dairy
      products and BFIs for egg products commonly consumed in Europe. Strikingly, only
      a limited number of compounds have been reported as markers for the intake of
      these products and none of them have been sufficiently validated. A series of
      challenges hinders the identification and validation of BFI for dairy and egg
      products, in particular, the heterogeneous composition of these foods and the
      lack of specificity of the markers identified so far. Further studies are,
      therefore, necessary to validate these compounds and to discover new candidate
      BFIs. Untargeted metabolomic strategies may allow the identification of novel
      biomarkers, which, when taken separately or in combination, could be used to
      assess the intake of dairy and egg products.

PMID- 30279748
TI  - A case of biventricular thrombi in a patient with dilated cardiomyopathy: Utility
      of multimodality imaging for diagnosis and management of treatment strategy.
AB  - A 54-year-old man was transferred to our hospital due to congestive heart failure
      and left ventricular thrombi. Transthoracic echocardiography (TTE) showed mobile
      "ball-like" not only left ventricular but also right ventricular thrombi
      associated with severe impaired left and right ventricular function. Contrast
      enhanced computed tomography (CT) and cardiac magnetic resonance imaging (MRI)
      also detected biventricular apical thrombi complicated with right renal
      infarction. Coronary angiography showed non-significant stenosis. Due to the
      mobility of thrombi and complication of systemic infarction, the surgical
      transatrial video-assisted removal of biventricular thrombi was performed and
      postoperative course has been uneventful over a period of 6 months.
      Endomyocardial biopsy performed during an operation showed no specific findings
      such as endomyocarditis, indicating the diagnosis of dilated cardiomyopathy
      (DCM). This is a rare case of DCM complicated with biventricular apical thrombi
      detected clearly by multimodality imaging such as TTE, contrast-enhanced CT and
      cardiac MRI, and surgical removal was performed successfully. <Learning
      objective: The incidence of biventricular thrombi is rare and has been reported
      to be associated with coagulation abnormality and severe ventricular dysfunction.
      The detection of ventricular thrombi using echocardiography is sometimes
      difficult, and treatment strategy often becomes a major topic of debate. The
      usefulness of multimodality imaging for the detection of ventricular thrombi
      leads to accurate diagnosis and provides helpful information regarding the
      selection of appropriate treatment.>.

PMID- 30279750
TI  - Left circumflex coronary artery to coronary sinus fistula diagnosed in infancy.
AB  - Coronary artery fistulas are rare anomalies, their incidence range from 0.1 to
      0.2% of congenital heart defects. The left circumflex coronary artery (LCX)
      fistula draining into the coronary sinus (CS) is a less common form, and most
      cases described in the literature were adult cases. We are describing this type
      of fistula in an 8-month-old asymptomatic female presenting with a continuous
      murmur over the pericordium. Electrocardiogram was normal. Echocardiography
      revealed a dilated LCX and CS with turbulent flow in CS; 2-D speckle tracking
      echocardiography revealed normal left ventricular strain with no regional wall
      abnormalities. Multidetector computed tomography demonstrated the fistula. As the
      patient was asymptomatic, with no ventricular dilatation or dysfunction, we
      decided conservatively. <Learning objective: Coronary artery fistulas are rare
      anomalies that require complementary diagnostic modalities. 2D echocardiography,
      color flow Doppler, 2D speckle tracking, and multidetector computed tomography
      are needed to delineate the anomaly and to conclude the prognosis and long-term
      follow-up plans.>.

PMID- 30279751
TI  - A case of fatal heart and liver failure accompanied by thyroid storm treated with
      prompt plasma exchange.
AB  - A 36-year-old man with a history of Graves' disease was admitted complaining of
      dyspnea. He was diagnosed with acute heart failure and severe liver dysfunction
      accompanied by thyroid storm. Left ventricular ejection fraction was 19%, and
      liver enzyme levels were markedly elevated followed with coagulation disorders.
      In addition to the conventional therapy, we performed plasma exchange emergently.
      Thyroid hormone levels promptly normalized, then his clinical condition improved.
      Finally, his cardiac and liver function almost normalized from a fatal condition
      without serious complications. Hyperthyroidism can cause myocardial and liver
      injury, hence thyroid hormone removal in acute phase is important. Prompt plasma
      exchange is effective in the acute phase for heart and liver failure accompanied
      by thyroid storm. <Learning objective: Thyroid storm is a life-threatening
      condition. Prompt reduction of serum free thyroid hormone is important in fatal
      conditions. Because plasma exchange (PE) can decrease serum thyroid hormone and
      improve critical condition, PE should be conducted emergently. In the present
      case, we promptly performed PE for the patient with potentially fatal heart and
      liver failure. We could treat him without any complication. We wish to emphasize
      the importance of prompt PE in acute phase of thyroid storm.>.

PMID- 30279752
TI  - Penetration of inferior vena cava filter strut through an introducer sheath
      inserted from the left internal jugular vein: An anatomical pitfall.
AB  - The report describes a case of penetration of an inferior vena cava filter (IVCF)
      strut through an introducer sheath inserted from the left internal jugular vein.
      A 64-year-old woman was admitted to our hospital with pulmonary embolism and
      lower extremity deep vein thrombosis. We attempted to implant a retrievable type
      IVCF via the left internal jugular vein. However, an unexpected resistance
      occurred during the advancement of the filter after passing the first few inches
      within the 8-Fr introducer sheath. Immediately, we checked the insertion site
      using fluoroscopy, which demonstrated penetration of the filter struts to the
      outside of the sheath. We speculate that a strong angulation in the vessel from
      the left internal jugular to superior vena cava might have contributed to this
      rare complication. <Learning objective: Penetration of an inferior vena cava
      filter (IVCF) strut through an introducer sheath is a rare complication. However,
      physicians should recognize that this complication could occur in cases of IVCF
      placement, especially when insertion is done via the left internal jugular
      vein.>.

PMID- 30279753
TI  - An infant with truncus arteriosus with situs inversus with single atrium: A case
      report.
AB  - Truncus arteriosus is a rare heart defect comprising <1% of congenital cyanotic
      heart disease. Rarely it may be associated with single ventricle, but association
      with single atrium is very rare. We report a case of truncus arteriosus (Van
      Praag type A2) with single atrium and single ventricle. <Learning objective: In
      our case truncus arteriosus was associated with single atrium, single ventricle,
      and situs inversus which is rare and has not been reported in the literature.>.

PMID- 30279754
TI  - Right-sided cardiac resynchronization therapy with defibrillator implantation in
      a patient with corrected transposition of great arteries and persistent left
      superior vena cava.
AB  - Patients with corrected transposition of great arteries (c-TGA) are generally
      known to develop atrioventricular block, systemic right ventricular dysfunction,
      and tricuspid regurgitation over time, which are associated with tachyarrhythmia
      and progressive heart failure. A 76-year-old man had been diagnosed with c-TGA.
      He developed a cardiopulmonary arrest while playing tennis, and an automated
      external defibrillator detected ventricular fibrillation (VF). Immediate
      cardiopulmonary resuscitation and intensive treatment were performed. He fully
      recovered without neurological sequelae. QRS duration was 172 ms.
      Echocardiography showed marked dysfunction and dyssynchrony of the systemic right
      ventricle (systemic right ventricular end-diastolic diameter/end-systolic
      diameter = 73/60 mm, systemic right ventricular ejection fraction = 34%). For
      secondary prevention and treatment of progressive heart failure, cardiac
      resynchronization therapy with defibrillator (CRT-D) implantation was
      recommended. Venography via the left cubital superficial vein revealed a
      persistent left superior vena cava (PLSVC) and giant coronary sinus that did not
      connect with the right superior vena cava (SVC). Because of the acute angle
      between the PLSVC and great cardiac vein, we selected a right-sided approach via
      the right SVC. We were finally able to deliver a coronary sinus lead to the
      lateral vein. CRT-D implantation can be achieved even in patients with c-TGA and
      PLSVC. <Learning objective: CRT-D implantation can be achieved even in a patient
      with c-TGA and PLSVC.>.

PMID- 30279755
TI  - Coronary vasospasm complicating cannabinoid hyperemesis syndrome.
AB  - Cannabinoid hyperemesis syndrome (CHS) is a clinical condition that was first
      described in 2004. The syndrome may occasionally be observed in long-term
      cannabis users and is characterized by a set of features: severe cyclic nausea
      and vomiting, recurrent epigastric or periumbilical pain, relief of symptoms with
      hot baths, and cannabis use cessation. The pathophysiology is not fully
      understood but is probably related to Cannabinoid-1 (CB-1) receptors
      dysregulation. On the other hand, there is also growing epidemiological evidence
      that cannabis smoking may trigger acute coronary syndrome (ACS) in young men. We
      describe the case of 41-year-old man with a long history of cannabis smoking who
      not only complained of recurrent epigastric but also of retrosternal pain. He had
      undergone several negative radiological or endoscopic investigations. During the
      last episode, electrocardiographic and echocardiographic changes were consistent
      with takotsubo cardiomyopathy. However, the patient was readmitted very soon with
      a ST-elevation myocardial infarction related to coronary vasospasm. While the
      link between CHS and ACS is not established, CHS patients with atypical pain
      should be investigated carefully to exclude any serious cardiac event. <Learning
      objective: Cannabinoid hyperemesis syndrome is a rare medical entity than can be
      observed in some long-term heavy cannabis users. While most patients usually
      complain of recurrent epigastric or periumbilical pain with negative
      investigations, the possibility of some serious cardiac event should not be
      neglected as cannabis seems also able to trigger coronary vasospasm in patients
      presenting with atypical pain or electrocardiographic changes.>.

PMID- 30279756
TI  - Transradial retrograde percutaneous transluminal angioplasty with stenting of
      long segment occlusion of subclavian artery.
AB  - We report a case of retrograde percutaneous transluminal angioplasty with
      stenting to chronically occluded upper limb vessels in a young female with
      Takayasu arteritis. A self-expanding stent (Supera peripheral stent system -
      Abbott Vascular, Santa Clara, CA, USA) was tracked retrogradely via ipsilateral
      radial access and the procedure was successful with good results. To our
      knowledge this is the first report of a Supera stent being tracked retrogradely
      through the radial artery. <Learning objective: This case demonstrates the
      feasibility of tracking and successful deployment of Supera stent
      transradially.>.

PMID- 30279758
TI  - A case of life-threatening supraventricular tachycardia storm associated with
      theophylline toxicity.
AB  - A 76-year-old man taking theophylline was admitted to our hospital with
      congestive heart failure and supraventricular tachycardia (SVT). After admission,
      he developed cardiogenic shock as a result of SVT storm, which was refractory to
      medical treatment including adenosine and electrical cardioversion. The serum
      theophylline concentration at admission was identified as toxic. Therefore,
      theophylline toxicity was considered as a major cause of the SVT storm.
      Hemodynamic stability was achieved by using mechanical circulatory support.
      Additionally, continuous hemodiafiltration was performed to remove theophylline,
      and it was effective for suppression of SVT. The patient was successfully weaned
      off mechanical circulatory support. After the patient's general status had
      improved, an electrophysiological study was performed, and it showed orthodromic
      atrioventricular reentrant tachycardia with a right free wall accessory pathway.
      Radiofrequency catheter ablation was successfully performed. <Learning objective:
      SVT is often hemodynamically stable and medically well-controllable with
      adenosine. However, SVT is occasionally refractory or life-threatening under
      specific conditions such as theophylline toxicity, since theophylline has an
      inhibitor effect on adenosine. Mechanical circulatory support should be used in
      case of life-threatening SVT storm associated with theophylline toxicity.>.

PMID- 30279757
TI  - Comprehensive arrhythmic surgery for sustained ventricular tachycardia revisited.
AB  - A 68-year-old woman with a history of old inferior myocardial infarction was
      admitted because of sustained ventricular tachycardia. Double vessel coronary
      disease was found with subtotal obstruction of the right coronary artery (#1) and
      severe stenosis of the left circumflex coronary artery (#13). Dilated left
      ventricle with a large ventricular aneurysm at the inferior wall and severely
      reduced systolic function were also present. A comprehensive surgical ablation
      using subendocardial resection and cryoablation was performed in combination with
      aneurysmectomy, left ventricular reconstruction, and coronary bypass grafting to
      the circumflex coronary artery. An implantable cardioverter-defibrillator was
      also implanted. She has remained well without recurrence of sustained ventricular
      tachycardia for one year. Although radiofrequency catheter ablation is nowadays
      considered a first-line therapy for patients with sustained ventricular
      tachycardia, surgical ablation remains a valuable option for selected patients,
      particularly for those requiring left ventricular aneurysmectomy and coronary
      artery bypass grafting, in order to gain a better long-term prognosis through
      total cure of ventricular tachycardia. <Learning objective: Although
      radiofrequency catheter ablation is nowadays considered a first-line therapy for
      patients with sustained ventricular tachycardia, surgical ablation remains a
      valuable option for selected patients, particularly for those requiring left
      ventricular aneurysmectomy and coronary artery bypass grafting, in order to gain
      a better long-term prognosis through total cure of ventricular tachycardia.>.

PMID- 30279759
TI  - Giant left atrial appendage aneurysm: A case of mistaken identity.
AB  - Left atrial appendage (LAA) aneurysm is a rare condition that can be congenital
      or acquired. Most cases are discovered incidentally. However, the most frequent
      clinical presentations include supraventricular tachycardias and systemic
      embolization. Most cases in the literature were treated by resection of the LAA,
      and it has been recommended to perform LAA resection even in asymptomatic
      patients in order to prevent thromboembolic events. Here, we describe the safe,
      conservative management of a patient who was initially felt to have congenital
      partial absence of the left pericardium but at surgery the diagnosis of LAA
      aneurysm was established. <Learning objective: LAA aneurysm is a rare condition
      which has typically been managed with prompt surgical excision due to the
      perceived high risk of thromboembolic events. Our case demonstrates that LAA
      aneurysm and its associated arrhythmias can be treated medically with AV-nodal
      blockade and oral anticoagulation in the asymptomatic patient. Conservative
      management of asymptomatic patients with a LAA aneurysm with close monitoring of
      LAA size may allow for a delay or possible avoidance of surgery.>.

PMID- 30279760
TI  - Silent cardiac tumor with neurological manifestations.
AB  - Atrial myxoma is rare and can be completely asymptomatic. However, an untreated
      myxoma may result in catastrophic events. Diagnosis is usually suggested by
      echocardiography, and other imaging modalities can add important information.
      Myxoma can be cured surgically, and histological analysis usually gives the
      definite diagnosis. This article describes the case of a 61-year-old woman whose
      clinical presentation of an atrial myxoma was a stroke. Echocardiographic
      findings were highly suggestive of a cardiac myxoma. However, cardiac magnetic
      resonance showed unusual features for myxoma, since the mass was hyperintense in
      T1-weighted images and hypointense in T2-weighted sequences. Histology confirmed
      myxoma and the patient was surgically treated. This case enhances the importance
      of multimodality imaging in the differential diagnosis of cardiac masses.
      <Learning objective: This case report describes a patient presenting with a
      stroke. Echocardiography demonstrated an atrial mass, suggestive of a cardiac
      myxoma. Cardiac magnetic resonance revealed a mass with unusual features for a
      myxoma, namely hyperintensity in FSE-T1 and hyposignal in FSE-T2. The authors
      make a brief summary of the neurological manifestations and imaging
      characteristics of the atrial myxoma. The importance of multimodality imaging in
      the diagnosis of cardiac tumors is also discussed.>.

PMID- 30279762
TI  - Kounis syndrome type I in a victim of cardiopulmonary arrest after hymenoptera
      sting.
AB  - Kounis syndrome is a relatively rare entity in which allergic or hypersensitivity
      reactions (including anaphylaxis) coexist with acute coronary syndromes. We
      report a case of Kounis syndrome type I variant in a 51-year-old male, victim of
      an out-of-hospital cardiac arrest a few minutes after a hymenoptera sting. Iotan
      hospital cardiopulmonary resuscitation was provided and return of spontaneous
      circulation was achieved. The post-resuscitation electrocardiogram revealed ST
      segment elevation in leads II, III, aVF, and ST depression in leads V2, V3, and
      V4. After administration of corticosteroids, antihistamines, nitrates, and a
      calcium-channel blocker the electrocardiogram rapidly returned to normal. There
      was no elevation in markers of myocardial necrosis and the coronary angiography
      revealed normal coronary arteries. According to the clinical course and the
      laboratory findings the diagnosis of Kounis syndrome type I variant was made.
      Only a few cases of Kounis syndrome in the setting of cardiopulmonary arrest have
      been published. We believe that in these cases, the recognition of the main
      underlying cause that lead to arrest (acute coronary syndrome or severe
      anaphylactic reaction) plays an important role in the choice of the most
      appropriate treatment for the patient. <Learning objective: Kounis syndrome is a
      rare clinical condition. However, every cardiologist should be capable of
      diagnosing it, because under specific circumstances it can be life-threatening.>.

PMID- 30279761
TI  - Role of 99mTc-sestamibi gated SPECT/CT myocardial perfusion imaging in the
      management of patients with myocardial bridging and its correlation with coronary
      angiography.
AB  - Myocardial bridging (MB)-a congenital coronary abnormality in its severe form
      leads to myocardial edema, fibrosis, and ischemia due to coronary artery
      compression during systole and early part of the diastole. This study evaluated
      the hemodynamic significance of MB by detecting severity and extent of perfusion
      abnormality using 99mTc-sestamibi (MIBI) gated single photon emission computed
      tomography (SPECT)/CT myocardial perfusion imaging (MPI), its correlation with
      coronary angiography and role in patient's management. Five patients with
      complaints of atypical chest pain, exertional angina, or dyspnea underwent
      stress/rest 99mTc-MIBI SPECT/CT MPI. The gated stress and rest SPECT/CT images on
      17 segment model using quantitative gated-SPECT (QGS) softwarewere analyzed and
      compared with coronary angiography. Four out of five patients showed reversible
      perfusion defect in the left anterior descending (LAD) territory segments
      involved with myocardial bridging (3 patients had already proven MB; while MB was
      detected in 1 patient after MPI). The fifth patient with MB in the distal LAD
      revealed normal myocardial perfusion. All the patients were conservatively
      managed either due to small reversible perfusion defects or normal study except
      one patient. The gated SPECT/CT MPI of five patients with MB in the present study
      revealed their perfusion status, information on myocardial wall thickening,
      contractility, and ejection fraction. <Learning objective: Myocardial bridging
      may be one of the underlying causes for angina or sudden death even in absence of
      cardiovascular risk factors. The proven or clinical suspicious myocardial
      bridging in patients with typical/atypical chest pain and low probability of
      atherosclerosis should be evaluated with gated SPECT/CTMPI. It helps in detection
      of coronary artery disease along with severity and extent of myocardial ischemia
      for their further management.>.

PMID- 30279763
TI  - A case of heparin-induced thrombocytopenia with subacute stent thrombosis,
      multiple cerebral infarction, and acute limb ischemia.
AB  - Heparin-induced thrombocytopenia (HIT) is an adverse immune-mediated drug
      reaction that is associated with thromboembolic complications. We report the case
      of an 82-year-old man with unstable angina pectoris who suffered from recurrent
      arterial thromboembolism due to HIT. Coronary angiography (CAG) was performed
      while we administered unfractionated heparin bolus. CAG showed triple-vessel
      disease without left main coronary artery. We performed elective percutaneous
      coronary angioplasty (PCI) to the left anterior descending coronary artery (LAD).
      The sudden thrombus formation in the LAD occurred during the procedure. We
      suspected HIT and administered argatroban. We deployed four everolimus-eluting
      stents in the LAD and intra-aortic balloon pumping (IABP) support was started.
      The platelet counts were rapidly reduced almost 50% next day after PCI and IgG
      specific anti-PF4/heparin antibodies were elevated. Multiple cerebral infarctions
      were detected by magnetic resonance imaging after the PCI. The patient received
      the continuous argatroban administration and IABP support for 4 days. Subacute
      stent thrombosis occurred after quitting argatroban. We performed thrombus
      aspiration and fibrinolytic treatment. Finally we re-inserted IABP and stabilized
      the hemodynamic state. Right popliteal arterial thromboembolism occurred after
      emergency PCI. Argatroban is essential and following oral anticoagulant therapy
      is necessary to prevent thromboembolic complications. <Learning objective:
      Heparin-induced thrombocytopenia (HIT) is an adverse immune-mediated drug
      reaction that is associated with thromboembolic complications. The incidence of
      HIT in patients who received unfractionated heparin is reported to be 0.1- 1%. We
      should be aware of HIT when thromboembolic complications occur during the
      percutaneous coronary intervention procedure. Argatroban is essential and
      following oral anticoagulant therapy is necessary to prevent thromboembolic
      complications among patients with HIT.>.

PMID- 30279764
TI  - Ascending aortic dissection in a young patient using a synephrine-containing
      workout supplement.
AB  - Aortic dissection in young patients presents a clinical and diagnostic challenge.
      Atypical symptoms of ascending aortic dissection can delay presentation and
      diagnosis. Here, we describe a patient with delayed diagnosis of an atypical
      presentation of ascending aortic dissection after using a synephrine-containing
      pre-workout supplement. The diagnosis was initially missed on computed
      tomography, but subsequently made on echocardiography. This is the first reported
      case of ascending aortic dissection in the setting of synephrine supplementation.
      This case illustrates a potential cardiovascular adverse effect of synephrine and
      highlights the need for clinical trials without conflicts of interest assessing
      its safety. <Learning objective: The aims of this report are to highlight the
      diagnostic challenge of an atypical presentation of ascending aortic dissection
      and to illustrate a potential cardiovascular adverse effect of synephrine
      supplementation.>.

PMID- 30279765
TI  - An unusual cause of cardiogenic shock: Left atrial compression by a spontaneous
      rupture of an aneurysm of the descending thoracic aorta.
AB  - A 77-year-old woman presented with a feverish hemodynamic collapse, acute
      respiratory distress, and dorsal pain, initially treated as a septic shock.
      Transthoracic echocardiogram revealed an impressive compression of the left
      atrial cavity, by an extrinsic mass preventing the left ventricle from refilling.
      Thoracic computed tomography revealed a large hemomediastinum emerging from an
      aneurysm of the descending thoracic aorta compressing the left atrium. The
      patient died in refractory cardiogenic collapse. <Learning objective: In the
      management of cardiovascular collapse, the understanding of the mechanism or the
      cause is essential. For this purpose, echocardiogram is a fast and indispensable
      tool, sometimes allowing discovering surprising etiology.>.

PMID- 30279766
TI  - Familial Carney complex with biatrial cardiac myxoma.
AB  - We report a case of Carney complex (CNC) with biatrial cardiac myxoma. The
      patient had left and right atrial myxomas which were resected in a surgery. She
      showed bilateral adrenal tumors and multiple mammary tumors. She had pigmentation
      on her lower lip. Previously, her daughter was also diagnosed with CNC with
      cardiac myxoma. Both of them showed mutations in the PRKAR1A gene. <Learning
      objective: Carney complex is a syndrome with skin pigmentation, myxomas, and
      endocrine abnormalities. It is an autosomal dominant disease and shows PRKAR1A
      gene mutation. We experienced a rare case of familial Carney complex with
      biatrial cardiac myoxomas found by echocardiography and treated surgically.>.

PMID- 30279767
TI  - Simultaneous transcatheter aortic valve implantation and off-pump coronary artery
      bypass grafting for Takayasu arteritis.
AB  - We report a patient who underwent simultaneous transcatheter aortic valve
      implantation and off-pump coronary artery bypass grafting for Takayasu arteritis
      with diffuse porcelain aorta. The patient was a 59-year-old female with severe
      aortic stenosis and regurgitation, as well as both coronary ostial stenosis and
      porcelain aorta. Bilateral internal thoracic arteries were unavailable due to
      Takayasu arteritis. Therefore, composite radial artery with in-situ
      gastroepiploic artery was used as graft material. Radial artery was anastomosed
      to left anterior descending artery and posterior descending artery sequentially.
      Surgical procedures were successfully accomplished and major perioperative
      complications did not occur. <Learning objective: Takayasu arteritis is a rare
      disease with vasculitis of aorta and its main branches. In addition, it is
      associated with a low incidence of coronary ostial stenosis and coronary ischemia
      can be fatal. Porcelain aorta with aortic valve lesion also complicates with
      Takayasu arteritis and it makes difficult to perform cardiac surgery. The optimal
      surgical strategy and process for those who combined with coronary ostial
      stenosis, aortic valve lesion and porcelain aorta remains a subject of debate.>.

PMID- 30279768
TI  - Ruptured pseudo-aneurysm of the mitral-aortic intervalvular fibrosa - A 3D
      transesophageal echocardiographic depiction.
AB  - Pseudo-aneurysm of the mitral-aortic intervalvular fibrosa (MAIVF) is a rare
      complication of native or prosthetic valve endocarditis. Good imaging is the key
      to successful diagnosis of this rare entity. This report describes a pseudo -
      aneurysm of the MAIVF rupturing into left atrium in a patient with double valve
      replacement with special reference to 3-dimensional transesophageal
      echocardiographic imaging. <Learning objective: Transesophageal real-time 3
      dimensional echocardiography provides useful information in understanding the
      anatomy of pseudo-aneurysm of mitral-aortic intervalvular fibrosa and
      differentiating it from abscess. In our case, it clearly showed a pouch-like,
      pulsatile structure moving in and out of the left atrium. This can be of immense
      help in formulating an appropriate surgical or device strategy.>.

PMID- 30279769
TI  - A rare case of eosinophilic granulomatosis with polyangiitis complicated with
      progressive pericardial effusion.
AB  - A 44-year-old woman had a 15-year history of asthma and had recently been treated
      for sinusitis and unidentified limb eruption. She had presented at a nearby
      clinic with inspiratory chest pain one week before hospitalization, and was
      diagnosed as having eosinophilic pneumonia based on peripheral blood eosinophilia
      and ground glass opacities in the right lung field, without pericardial effusion,
      as detected by chest computed tomography. She additionally presented with a
      feeling of chest tightness, and extensive pericardial effusion appeared within a
      week. She developed heart failure on admission, and we performed
      pericardiocentesis. We gave a clinical diagnosis of acute probable
      myopericarditis as the cause of pericardial effusion based on pleuritic chest
      pain, pericardial effusion, and elevation of cardiac enzymes, as well as
      eosinophilic granulomatosis with polyangiitis (EGPA) based on eosinophilia, her
      history of sinusitis, asthma, and migratory pulmonary opacities. We initiated
      oral prednisone 25 mg daily and pericardial effusion disappeared. In patients
      with EGPA, cardiac involvement is more serious than the involvement of other
      organs, and is associated with a poor prognosis. In this report we describe a
      rare case of EGPA complicated with progressive pericardial effusion and discuss
      the importance of the early diagnosis and treatment of EGPA. <Learning objective:
      Eosinophilic granulomatosis with polyangiitis (EGPA), or Churg Strauss syndrome,
      is a multisystem disorder. It is important for patients with EGPA complicated
      with cardiac involvement to be diagnosed and treated early because cardiac
      involvement may lead to a fatal outcome.>.

PMID- 30279770
TI  - Normalization of biventricular strain post steroid treatment of effusive
      constrictive pericarditis.
AB  - Peak left ventricular strain measured by speckle tracking echocardiography has
      previously been shown to normalize following pericardectomy in constrictive
      pericarditis, as indicated by an increase of the strain ratio between the lateral
      wall and septum. Here we present a case of effusive constrictive pericarditis
      treated with corticosteroids. Pre-treatment we observed reduced contractility of
      the lateral walls of both ventricles as measured by peak strain, with sparing of
      overall septal function, but with hypercontractility of the basal septal segment.
      Septal and lateral wall function normalized with corticosteroid treatment. Our
      observations from this case prompts investigation into the value of
      lateral/septal wall strain ratios in both ventricles for quantitatively
      monitoring the response of constrictive pericarditis to medical therapy.
      <Learning objective: Change in peak strain ratios between the lateral and septal
      walls of both ventricles may be a novel marker of response to medical therapy in
      effusive constrictive pericarditis.>.

PMID- 30279771
TI  - Fistula formation following repair of a pseudoaneurysm of the mitral-aortic
      intervalvular fibrosa - A rare complication.
AB  - The mitral-aortic intervalvular fibrosa is an avascular fibrous structure
      connecting the mitral and aortic annuli that is prone to pseudoaneurysm
      formation. Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a known
      complication of many conditions such as infective endocarditis and valvular
      surgery. It requires surgical correction. Its long-term consequences are little
      known. We present in this report the case of a 62-year-old male with history of
      pseudoaneurysm of the mitral-aortic intervalvular fibrosa repair and redo mitral
      and aortic prosthetic valve replacements. After five years of asymptomatic follow
      up, the patient presented with sudden-onset heart failure. Echocardiographic
      investigation demonstrated two aorto-atrial fistulae at the site of his previous
      repair and adequate function of both prosthetic valves. The fistulae were
      repaired and the prosthetic valves were left in place. This represents a
      potential late surgical complication of pseudoaneurysm of the mitral-aortic
      intervalvular fibrosa. <Learning Objectives: This case report describes a rare
      complication occurring many years after the repair of a pseudoaneurysm of the
      mitral-aortic intervalvular fibrosa. Surgical and follow-up history is discussed
      to familiarize clinicians with this atypical presentation type.>.

PMID- 30279772
TI  - Right ventricular mobile thrombus in end-stage hypertrophic cardiomyopathy.
AB  - We report the first case of a mobile right ventricular apical thrombus in
      hypertrophic cardiomyopathy in the absence of right ventricular apical aneurysm.
      An 87-year-old man who had been diagnosed as having hypertrophic cardiomyopathy
      presented with gross peripheral edema and exertional dyspnea. He had been on
      warfarin, beta-blockade, and diuretics. Electrocardiograms indicated progression
      of the disease with atrial fibrillation, low voltage and prominent Q waves in the
      left precordial leads. Echocardiograms revealed ventricular septal and apical
      hypertrophy, hypokinetic distal left ventricle, and dilated and severely
      hypokinetic right ventricle. A mobile thrombus (18 mm * 18 mm) was detected in
      the right ventricular apex. Cardiac computed tomography and magnetic resonance
      imaging confirmed a large thrombus in the right ventricular apex. Late gadolinium
      enhancement was present in the interventricular septum and distal segments of
      both ventricles, indicating myocardial fibrosis and scar. A dilated and poorly
      contracting right ventricle, particularly right ventricular apex, in end-stage
      hypertrophic cardiomyopathy, associated with stagnant blood flow in the apex, was
      hypothesized as being responsible for right ventricular apical thrombus formation
      in the absence of right ventricular aneurysm. <Learning objective: This is the
      first report of a mobile thrombus in the right ventricle in hypertrophic
      cardiomyopathy. Since mobile right ventricular thrombi may cause life-threatening
      pulmonary embolism, and detection of thrombi in the right ventricular apex may be
      difficult by echocardiographic examination, we suggest the use of cardiac
      computed tomography and/or magnetic resonance imaging that are useful tools to
      detect right ventricular apical thrombi when severe right ventricular dysfunction
      is suspected in end-stage hypertrophic cardiomyopathy.>.

PMID- 30279773
TI  - A case of in-stent restenosis with pathologically proven chronic inflammation
      seven years after sirolimus-eluting stent implantation.
AB  - A 67-year-old man was admitted to our hospital due to chest pain at rest. Seven
      years previously, the patient underwent percutaneous coronary intervention (PCI)
      of the left ascending artery and implanted sirolimus-eluting stent (SES).
      Coronary angioscopy (CAS) performed at that time showed a white plaque at the SES
      site. Two years after the first PCI, repeat CAS demonstrated light yellow plaques
      at the SES site. At the time of his presentation to our hospital, coronary
      angiography showed in-stent restenosis at the SES site, and CAS demonstrated the
      plaque rupture with presence of dense yellow plaque and various thrombi. After
      distal protection, drug-eluting balloon treatment was performed. Collected
      specimens from culprit sites included foamy macrophages, cholesterin crystals,
      neutrophils, and fibrin, suggesting that progressive neoatherosclerosis at the
      SES site triggered the acute coronary syndrome. This study highlights the
      importance of ensuring careful patient follow-up after SES implantation.
      <Learning objective: After 1st generation drug-eluting stent implantation,
      careful follow up is warranted, as the process of neoatherosclerosis can be
      ongoing and contribute to in-stent restenosis.>.

PMID- 30279774
TI  - Primary cardiac rhabdomyosarcoma developed after receiving radiotherapy for left
      breast cancer 18 years prior.
AB  - The heart is an organ where primary malignant tumors rarely develop. In
      particular, the incidence of cardiac rhabdomyosarcoma (RMS) is extremely low. It
      has been reported that the risk of second malignant tumors in mediastinum is
      increased by radiotherapy in women with breast cancer. However, little is known
      about the association between irradiation to heart and cardiac RMS. Here, we
      report a case of a 68-year-old woman with primary cardiac RMS. She suddenly
      presented syncope at a workplace, and was taken to the emergency room at our
      hospital. Several imaging tests, including echocardiogram and cine magnetic
      resonance imaging, detected two tumors in the right ventricle (RV) and its
      outflow tract, which had almost obstructed the main trunk of the pulmonary artery
      (PA). To avoid sudden PA occlusion by the tumor, we emergently performed surgical
      excision of the tumors from the RV. Pathological analysis revealed that these
      tumors were embryonal type RMS. She had received radiotherapy after mastectomy
      for left breast cancer 18 years previously, and no recurrence of breast cancer
      had been detected. This cardiac RMS is considered as a second malignant tumor
      related to radiotherapy for breast cancer. <Learning objective: We experienced a
      68-year-old woman having two tumors of the RMS in RV, who had received
      radiotherapy for left breast cancer 18 years previously and had previously
      presented no recurrence. There is literature suggesting that radiotherapy may
      increase the risk of soft-tissue sarcoma in women with breast cancer. We should
      be aware of cardiac RMS as a second malignant tumor related to radiotherapy for
      breast cancer, although its incidence is extremely low.>.

PMID- 30279775
TI  - A case of unexpected early battery depletion caused by lithium cluster formation
      in implantable cardioverter-defibrillator.
AB  - Device failure from unexpected battery depletion is uncommon but can be life
      threatening. Lithium cluster formation at the cathode is a novel mechanism of
      sudden implantable cardioverter-defibrillator (ICD) battery depletion that was
      first reported in 2014. We report a rare case of a 78-year-old woman with an ICD
      battery failure due to lithium cluster formation. Although she had never received
      ICD therapy, the battery voltage had dropped from 2.9 V to 2.54 V (end of life)
      unexpectedly for only 2 days. The prevalence of this rare phenomenon was reported
      to be 0.004% in 2014. However, it had gone up to 0.21% in October 2016. Both
      device manufacturers and clinicians should be aware of this phenomenon, and
      remote monitoring systems and vibratory patient notifier alerts should be
      considered for early detection and early treatment. <Learning objective: Lithium
      cluster formation is a novel mechanism of premature ICD battery depletion that
      was first reported in 2014. Although the prevalence of this rare phenomenon was
      first reported as 0.004% in 2014, according to the data of St. Jude Medical, it
      had gone up to 0.21% in October 2016. We should be aware of this rare but
      important phenomenon and use remote monitoring systems and vibratory patient
      notifier alerts for early detection and treatment.>.

PMID- 30279776
TI  - Lex parsimoniae.
AB  - We present a noteworthy case of dual pathology in a 62-year-old female with
      recurrent chest pains and extensive cardiac risk factors. From computed
      tomography coronary angiography, a left anterior descending artery lesion was
      identified and successfully revascularized with a drug-eluting stent. Due to
      persistent chest pain, further investigation revealed a descending aortic
      dissection, which was conservatively managed. This case highlights the potential
      challenges of diagnosis in dual pathologies and emphasizes initiating appropriate
      investigations. <Learning objectives: It is important to consider all
      differential diagnoses in atypical presentations of possible acute coronary
      syndrome. As clinical presentations and risk factors may be similar, initiating
      appropriate diagnostic and management pathways are crucial to avoid
      misdiagnosis.>.

PMID- 30279777
TI  - Tricuspid stenosis: An emerging disease in cardiac implantable electronic devices
      era. Case report and literature review.
AB  - Tricuspid valve dysfunction and in particular tricuspid stenosis has recently
      been described secondary to cardiac implantable electronic devices. The valve is
      subjected to different mechanisms of injury related to the endocardial lead
      passing through its plane. The lead can form a loop or perforate one of the
      leaflets and initiate inflammatory response and fibrotic changes. Multimodality
      cardiac imaging is required to diagnose this clinical entity and decide on the
      best treatment plan. Here we present a case of a young female who developed
      tricuspid stenosis secondary to permanent pacemaker lead that was implanted 24
      years before. We performed a review for all cases reported in the literature with
      a similar condition and various treatment approaches. <Learning objectives: 1.
      Tricuspid valve dysfunction can develop secondary to cardiac implantable
      electronic devices. Tricuspid regurgitation is the most common valve lesion
      however, tricuspid stenosis is reported as well. 2. Endocardial leads can cause
      injury to the valve initiating a cascade of inflammatory response and fibrosis.
      3. Trans-thoracic echocardiography is the initial diagnostic modality but
      visualization of lead injury requires further cardiac imaging such as cardiac
      computed tomography and trans-esophageal echocardiography. 4. Various treatment
      modalities are reported in the literature; medical therapy, percutaneous
      valvoplasty; and surgery.>.

PMID- 30279778
TI  - Acute myocardial infarction due to left main embolization of calcified tissue
      from mitral valve subapparatus.
AB  - An 81-year-old woman was referred for primary angioplasty due to a myocardial
      infarction. Upon her arrival, the patient was in cardiogenic shock.
      Coronarography revealed a large filling defect within the left main coronary
      artery. Thromboaspiration was performed, obtaining thrombotic material and tissue
      of different consistencies. Balloon angioplasty in the left anterior descending
      and left main arteries was performed, resulting in incomplete reperfusion,
      leading to irreversible electromechanical dissociation. Analysis of the aspirated
      material was consistent with thrombus, atheroma, and calcified tissue. Autopsy
      revealed a heavily calcified mitral valve, and distal embolization of amorphous
      material in the microvasculature identical to that found in the mitral valve
      subapparatus. <Learning objective: Acute myocardial infarction due to left main
      embolization of tissue from mitral valve subapparatus is a rare condition but
      lethal. Early recognition of this condition is important for establishing the
      best option of treatment, between a percutaneous or surgical approach.>.

PMID- 30279779
TI  - Dual loop reentrant tachycardia with a combination of a localized reentry and a
      macro-reentry.
AB  - A 78-year-old woman presented 2 years after mitral valve replacement for
      rheumatic mitral stenosis with cardioversion-resistant atrial tachycardia (AT).
      Dual-loop AT was identified by activation mapping with the RhythmiaTM system
      (Boston Scientific, Marlborough, MA, USA) and confirmed by entrainment-mapping;
      one circuit with localized re-entry turned around the scar on the posterior left
      atrium and the other circuit, which was macro re-entrant, turned around the left
      superior pulmonary vein (LSPV) using the PV-carina, the ridge beween the left
      atrial appendage and the LSPV, and the roof. The two wavefronts fused on the
      posterior wall close to the LSPV. Radiofrequency ablation of an area of slow
      conduction on the posterior wall changed the tachycardia to roof-dependent AT
      which was then terminated by completion of a roof line. <Learning objective: In
      this case report, we demonstrate the importance of using both conventional
      entrainment mapping methods and a novel ultra-high density mapping system to
      precisely understand the mechanism and appropriately terminate the complex atrial
      tachycardia in patients with prior atrial fibrillation ablation.>.

PMID- 30279780
TI  - Successful hybrid treatment with endovascular aorto-iliac revascularization and
      coronary bypass surgery in a patient with an advanced complex polyvascular
      disease.
AB  - A 72-year-old Japanese man was admitted to our hospital for effort chest pain and
      bilateral claudication. He was diagnosed as having severe ischemic heart disease
      and chronic bilateral aorto-iliac occlusions (Leriche syndrome) by a diagnostic
      angiography. Manifest collaterals via bilateral internal thoracic arteries (ITA)
      supplied sufficient blood flow for his lower limbs. We planned a two-stage
      operation for both the severe coronary artery disease and peripheral artery
      occlusive disease. He first underwent endovascular therapy (EVT) for bilateral
      aorto-iliac occlusion. One month later he underwent coronary artery bypass
      grafting (CABG) that was carried out for three coronary arteries with bilateral
      ITAs, also known as the internal thoracic artery, and the gastroepiploic artery.
      His chest symptoms and claudication were completely relieved and he was
      discharged uneventfully. We hereby suggest that EVT can be a safe, effective, and
      minimally invasive treatment to enable the patient to undergo CABG with all
      arterial grafts. <Learning objective: Patients with polyvascular disease are at a
      high risk for major vascular events. The priority among the revascularizations
      should be considered based on the less-invasiveness and better long-term patency.
      Hybrid treatment of EVT and CABG could be one of the choices among such
      patients.>.

PMID- 30279781
TI  - Coronary artery bypass graft pseudoaneurysm from saphenous vein graft stent
      fracture.
AB  - Saphenous venous graft (SVG) pseudoaneurysms are a rare complication of coronary
      artery bypass grafting (CABG). An 85-year-old man with CABG and a distal SVG
      stent presented with dyspnea. Chest computed tomography (CT) revealed a large
      partially thrombosed pseudoaneurysm at the distal SVG with stent fracture.
      Endoluminal exclusion of the distal SVG pseudoaneurysm using a covered stent was
      performed. Follow-up chest CT and angiography showed persistent pseudoaneurysm
      filling and enlargement. The SVG proximal to the pseudoaneurysm was embolized
      with coils to reduce rupture risk. Following embolization, the patient's left
      ventricular ejection fraction was moderately depressed but the patient remained
      stable and was discharged. <Learning objective: Saphenous venous graft
      pseudoaneurysms are a rare post-operative complication of coronary artery bypass
      graft procedures with a risk of impending rupture if left untreated. Fracture of
      a vein graft stent is an even further unique etiology of pseudoaneurysms. Covered
      stents are a practical therapeutic option for the treatment of vein graft
      pseudoaneurysms, especially in high risk patients who are not surgical
      candidates.>.

PMID- 30279782
TI  - Disopyramide as rescue treatment in a critically ill infant with obstructive
      hypertrophic cardiomyopathy refractory to beta blockers.
AB  - Hypertrophic obstructive cardiomyopathy (HOCM) is the most common known cause of
      sudden death in children beyond infancy and in young athletes. Cases reported
      indicate that steroid-induced HOCM is usually a benign disorder. The
      normalization of cardiac morphological changes and clinical signs observed after
      the discontinuation of steroid therapy indicates that the effects on cardiac
      muscle are dose-dependent and reversible. However, the management of patients
      with symptomatic-HOCM presenting in infancy represents a major challenge because
      left ventricular outflow tract obstruction is a major risk factor associated with
      increased mortality in pediatric patients. We report a critically ill infant with
      steroid-induced HOCM resistant to beta-blockers who was successfully treated with
      disopyramide without relevant adverse events. Adult guidelines and pediatric
      experts suggest pharmacological therapy with beta-blockers or verapamil as the
      first- and second-line approach. However, these drugs are not always an option,
      especially in critical patients, hence, alternative therapeutic options are
      required. For these cases, disopyramide could be an alternative drug in spite of
      the little evidence on its safety and efficacy in pediatric patients. Our
      experience supports this cause, and the need for prospective studies on its use
      in the management of hypertrophic cardiomyopathy in children. <Learning
      objective: Patients with symptomatic-HOCM resistant to first-line therapy with
      beta-blockers represent a challenge and are often referred for advanced care. In
      children, many authors suggest that disopyramide in combination with beta
      blockers could be a useful adjunct therapy option in these cases, resulting in
      decrease of left ventricular outflow tract obstruction, symptoms, and survival
      improvement, without significant pro-arrhythmia mortality.>.

PMID- 30279783
TI  - Left superior pulmonary venous thrombosis complicated with splenic infarction
      after video-assisted thoracoscopic left upper lobectomy.
AB  - A 72-year-old man underwent video-assisted thoracoscopic left upper lobectomy for
      small cell lung cancer. After 16 days, he experienced epigastric abdominal pain
      and vomiting, and was taken by ambulance to our hospital. Contrast-enhanced
      computed tomography (CT) showed a propagation of thrombus in the stump of the
      left superior pulmonary vein (LSPV) complicated with splenic infarction. The
      patient received anticoagulation therapy with heparin and warfarin, and further
      progression of the thrombus or any systemic embolic event was not observed during
      hospitalization. Here, we report a patient presenting with LSPV thrombosis
      complicated with splenic infarction after video-assisted thoracoscopic surgery
      (VATS), and describe several months follow-up CT imaging results after
      administration of an oral anticoagulation therapy. <Learning objective: Pulmonary
      venous thrombosis after lung surgery is a rare, but critical, condition. Only few
      cases have been previously reported and all cases described LSPV thrombus. We
      also demonstrated LSPV thrombus after VATS lobectomy, and clearly showed follow
      up results after anticoagulation therapy. Our case indicates the need for
      periodic CT imaging follow-up after left upper lobectomy and may call attention
      to thoracic surgeons, internal medicine, and cardiology physicians regarding this
      complication.>.

PMID- 30279784
TI  - Acute necrotizing eosinophilic myocarditis complicated by complete
      atrioventricular block promptly responded to glucocorticoid therapy.
AB  - Acute myocarditis is frequently accompanied with conduction disturbances.
      Complete atrioventricular (AV) block may occur in acute myocarditis, but rarely
      in eosinophilic myocarditis. Acute necrotizing eosinophilic myocarditis, the most
      severe form of eosinophilic myocarditis, is generally fatal, and rarely
      complicated by complete AV block. We report a case of a 66-year-old woman with
      acute necrotizing eosinophilic myocarditis who presented with general malaise and
      nausea. She suddenly fell into cardiogenic shock because of complete AV block and
      worsened heart failure. Ultrasound cardiography revealed pericardial effusion,
      edematous myocardium, and reduced contractility of the left ventricle. The
      biopsied specimens showed marked interstitial infiltration with predominant
      eosinophils accompanied with myocardial necrosis. Oral administration of
      glucocorticoid in moderate dose promptly resolved the complete AV block, her
      clinical symptoms, and cardiac function. We recognized that acute necrotizing
      eosinophilic myocarditis can be complicated by complete AV block. Steroid therapy
      could be effective in the treatment of conduction disturbance as well as
      myocardial inflammation. <Learning objective: We experienced a case of acute
      necrotizing eosinophilic myocarditis complicated by complete atrioventricular
      block. This case report documents the rare complication of acute necrotizing
      eosinophilic myocarditis and the great benefit of early steroid therapy for the
      condition.>.

PMID- 30279785
TI  - Left atrial ball thrombus after edge-to-edge mitral valve repair.
AB  - A thrombus can develop in the left atrium during atrial fibrillation because the
      loss of contractile function leads to blood flow stasis. Anticoagulation therapy
      is indicated for prevention of systemic embolism, usually maintaining an
      international normalized ratio between 2 and 3. Rarely a massive thrombosis
      develops in the atrium resulting in a peduncolated ball valve thrombus or in a
      free-floating thrombus. These two conditions are characterized by variables in
      the physical findings. Such masses are hazardous and upon discovery surgical
      treatment, often in emergency, is mandatory. We present here the case of a
      patient who developed an unnoticed huge left atrial ball thrombus despite
      warfarin therapy after previous mitral valve surgery. <Learning objective: Risk
      of atrial thrombosis threatens patients suffering from atrial fibrillation. The
      presence of a ring and a modified valve anatomy following a surgical repair could
      represent an additional drive in the thrombus formation pathway. A free-floating
      ball thrombus in the left atrium is an unusual occurrence that may cause fatal
      systemic emboli or left ventricular inflow obstruction, often resulting in sudden
      death. In such cases, even in the absence of symptoms, prompt surgical excision
      is recommended.>.

PMID- 30279786
TI  - Improvement of pulmonary arterial hypertension following medication and shunt
      closure in a BMPR2 mutation carrier with atrial septal defect.
AB  - Mutation of the BMPR2 gene is the most common genetic cause of pulmonary arterial
      hypertension (PAH). Although there have been some reports of BMPR2 mutation
      carriers among PAH patients with congenital heart disease, there have been few
      reports of their treatment. Here, we describe a 13-year-old female BMPR2 mutation
      carrier who presented with heritable PAH and atrial septal defect (ASD). She
      complained of fatigue, and cardiac catheterization showed a mean pulmonary artery
      pressure (PAP) of 56 mmHg, a pulmonary vascular resistance (PVR) of 8 Wood units
      and a pulmonary to systemic blood flow ratio (Qp/Qs) of 1.3. Following 2 years of
      medication therapy, the mean PAP had decreased to 30 mmHg, the Qp/Qs had
      increased to 2.7, and her symptoms persisted. We closed the ASD interventionally,
      and her symptoms improved after closure. Medication therapy was continued. Four
      years after closure, the PAH had improved with a mean PAP of 20 mmHg and a PVR of
      3.1 Wood units. To the best of our knowledge, this is the first report of PAH
      improvement following medication and ASD closure in a BMPR2 mutation carrier with
      heritable PAH. ASD closure following medication appears to be effective in some
      ASD patients with heritable PAH. <Learning objective: Mutation of the BMPR2 gene
      is the most common genetic cause of pulmonary arterial hypertension (PAH).
      Heritable PAH with BMPR2 mutations has been reported to have a poorer prognosis
      once PAH has developed. Recent reports have described treatment of atrial septal
      defect (ASD) patients with PAH by surgical or interventional ASD closure
      following medication therapy. This case suggests that medication followed by ASD
      closure could also be effective for BMPR2 mutation carriers with ASD and
      heritable PAH.>.

PMID- 30279787
TI  - Subacute effusive-constrictive pericarditis: Echocardiography-guided diagnosis
      and management.
AB  - A 49-year-old man presented with flu-like symptoms of two weeks.
      Electrocardiogram showed diffuse ST elevation. Blood samples revealed severe
      renal failure and moderate inflammatory results. Echocardiogram showed large
      pericardial effusion, dilated inferior vena cava, but no right ventricular
      collapse. The patient underwent hemodialysis, after which he developed clinical
      signs of cardiac tamponade with echocardiographic features of collapse of the
      right ventricle. Pericardial drainage was then performed revealing purulent fluid
      of 800 ml. Streptococcus agalactiae was found in the cultures of urine, blood,
      and pericardial fluid. Despite removal of the pericardial fluid, echocardiogram
      failed to show any improvement in dilated inferior vena cava and estimated right
      atrial pressure remained elevated. Thus, a diagnosis of subacute effusive
      constrictive pericarditis was made. Following antibiotic treatment for purulent
      pericarditis, early pericardiectomy was performed under transesophageal
      echocardiographic monitoring which successfully guided surgeons to careful
      removal of thick and adhesive visceral pericardium as well as an additional
      Waffle procedure resulting in significant clinical and hemodynamic improvement.
      Echo-guided approach is most practical in establishing the diagnosis of effusive
      constrictive pericarditis and also most helpful in obtaining successful surgical
      results. <Learning objective: Diagnosis of effusive-constrictive pericarditis is
      difficult and is not often made because of mixtures of clinical findings
      associated with effusion/tamponade and constriction. Echo-guided approach is most
      practical in establishing the diagnosis by detecting absence of normalization in
      dilatation of the inferior vena cava after pericardial drainage. Also, since
      careful removal of visceral pericardium is mandatory, transesophageal
      echocardiographic monitoring during pericardiectomy plays an essential role in
      obtaining successful surgical results.>.

PMID- 30279788
TI  - Organophosphate poisoning presenting as out-of-hospital cardiac arrest: A
      clinical challenge.
AB  - Out-of-hospital cardiac arrest (OHCA) remains a challenge for physicians since
      effective management and definitive salvage depend upon correct determination of
      the etiology and the extent of injury. Definitive diagnosis of organophosphate
      poisoning (OP) requires physicians' clinical awareness of a typical toxidrome,
      that is, characteristic signs and symptoms of poisoning, and laboratory
      confirmation. Here we report a case of an OHCA patient with OP, which was
      initially misdiagnosed as an acute ST segment elevation myocardial infarction
      based on the patient's medical history and clinical manifestations. <Learning
      objective: Organophospate poisoning is associated with an increasing mortality
      with widely used pesticides in the developing world. Differential diagnosis of
      out-of-hospital cardiac arrest should include such etiology that can be reversed
      by early intervention.>.

PMID- 30279789
TI  - Delayed cardiac tamponade 8 months after pulmonary vein isolation.
AB  - We herein report the case of a 55 year-old male who underwent pulmonary vein
      isolation (PVI) for paroxysmal atrial fibrillation. From 8 months after PVI,
      exertional dyspnea rapidly appeared. When he was referred to our hospital,
      massive pericardial effusion was observed by transthoracic echography. The
      pericardiocentesis revealed bloody pericardial effusion, and improved symptoms.
      Although aortic dissection, autoimmune disease, infection, metastatic pericardial
      tumor, primary pericardial tumor, and malignant neoplasm were considered as
      differential diagnosis, the cause of pericardial effusion failed to be found.
      From these findings, the cause of hemorrhagic pericardial effusion was considered
      delayed cardiac tamponade induced by PVI performed 8 months earlier. <Learning
      objective: Cardiac tamponade occurring after pulmonary vein isolation (PVI)
      procedure called delayed cardiac tamponade (DCT) is not widely recognized.
      However, mortality from DCT is far less than 5%, and we believe that it is a
      complication that requires due care. This report describes that DCT can occur
      even after 8 months of PVI.>.

PMID- 30279790
TI  - A case of ventricular fibrillation as a consequence of capecitabine-induced
      secondary QT prolongation: A case report.
AB  - Capecitabine is an oral fluoropyrimidine which can prolong QT interval. However,
      there have been no reports that capecitabine induced ventricular fibrillation
      (VF) due to secondary QT prolongation in patients with no structural heart
      disease. A 39-year-old woman developed VF during the chemotherapy of capecitabine
      for colon cancer. At the administration, corrected QT interval (QTc) was
      prolonged to 559 ms despite no evidence of organic heart disease. Discontinuation
      of capecitabline normalized the QTc (414 ms). During the follow-up of eight
      years, neither the QTc prolongation nor the recurrent VF has been detected. We
      report the rare case of capecitabine-related VF without any organic heart
      disease. <Learning objective: Capecitabine is an oral fluoropyrimidine carbamate
      commonly used to treat colorectal and breast cancer. Capecitabine has been
      reported to be associated with VF due to vasospasm. However, capecitabine is also
      associated with QT elongation. This is the first report to describe VF due to
      capecitabine-related secondary long QT syndrome in a patient with no cardiac
      heart disease. Physicians must carefully follow up patients during capecitabine
      chemotherapy with serial electrocardiograms.>.

PMID- 30279791
TI  - Therapeutic potential of tofogliflozin on nephrotic syndrome secondary to
      diabetic nephropathy.
AB  - Diabetic nephropathy (DN) is a critical complication in patients with type 2
      diabetes and regarded as a progressive disorder with a poor prognosis. The degree
      of albuminuria is associated closely with worse renal and cardiovascular
      outcomes. It is therefore important to achieve remission of proteinuria to avoid
      progression of DN and improve outcomes. Although a recent clinical trial
      demonstrated that a sodium glucose cotransporter 2 (SGLT2) inhibitor could
      improve cardiovascular and renal outcomes in cardiovascular high risk patients
      with type 2 diabetes, little is known whether SGLT2 inhibitors have favorably
      renal effects in patients with nephrotic syndrome associated with DN. Herein, we
      report a 54-year-old patient with refractory nephrotic syndrome accompanied by
      diabetic nephropathy. Tofogliflozin, a SGLT2 inhibitor, successfully increased
      urine volume, and reduced body weight, HbA1c, and urinary protein excretion (10.8
      to 2.6 g/day) during 24 weeks. His severe edema also was diminished after
      administration of tofogliflozin. This case indicates that an SGLT2 inhibitor may
      be a useful choice in the treatment of patients with diabetic nephropathy and the
      nephrotic syndrome. <Learning objective: Little is known whether SGLT2 inhibitor
      can attenuate nephrotic-range of proteinuria in patients with diabetic
      nephropathy. The present case is the first to demonstrate that tofogliflozin
      markedly reduced urinary protein excretion, body weight, and relevant markers in
      patient with nephrotic syndrome secondary to diabetic nephropathy. Thus, it is
      suggested that SGLT2 inhibitor has a therapeutic potential to attenuate nephrotic
      syndrome-related symptoms and markers as well as glycemic control.>.

PMID- 30279792
TI  - Differences of plaque characterization of high-intensity and non high-intensity
      plaques on non-contrast T1-weighted magnetic resonance imaging using angioscopy
      and optical coherence tomography.
AB  - Coronary high-intensity plaques (HIPs) visualized by non-contrast T1-weighted
      imaging (T1WI) in cardiac magnetic resonance (CMR) were associated with coronary
      events. We report a case of a 68-year-old man with an old myocardial infarction.
      He had undergone CMR to exclude new coronary artery disease, because he sometimes
      had an atypical chest symptom. The moderate stenosis in the right coronary artery
      (RCA) showed non HIP on non-contrast T1WI. We observed HIP in the proximal left
      anterior descending artery (LAD) without significant stenosis. Non HIP lesion in
      the RCA showed fibrous and calcified plaque without thrombus by optical coherence
      tomography (OCT) and angioscopy. On the other hand, the HIP lesion in the LAD
      showed lipid plaque with thrombus by OCT, and yellow plaque with mobile mixed
      thrombus by angioscopy. <Learning objective: These intracoronary modalities
      suggested that the HIP lesion is correlated with vulnerable plaques. Invasive
      coronary angiography (CAG) is considered the gold standard for the diagnosis of
      coronary disease, but CAG is thought not to be able to predict future events. Non
      contrast T1WI on CMR may be able to use for screening of vulnerable plaques.>.

PMID- 30279793
TI  - An adult case of Bland-White-Garland syndrome with collaterals from giant right
      coronary artery and bronchial artery.
AB  - Bland-White-Garland syndrome (BWG) is a congenital heart disease characterized by
      anomalous origin of left coronary artery from main pulmonary artery. The anomaly
      causes significant myocardial ischemia, mitral insufficiency, and high infant
      mortality. Several investigators have reported that the subjects who survived to
      adulthood showed extensive collateral flow from right coronary artery (RCA). We
      report a case of newly diagnosed BWG in an elderly patient who had well-developed
      collaterals from aneurysmal giant RCA and bronchial artery, which were identified
      by coronary angiography with multi-detector computed tomography. <Learning
      objective: Structural heart disease is occasionally hard to assess with invasive
      angiography. In this case, multi-detector computed tomography demonstrated
      complicated structure of anomalous coronary morphology including collateral
      sources from extra-cardiac anastomoses. The severity of anomaly related
      myocardial ischemia was evaluated by image fusion with radionuclide myocardial
      perfusion. Multimodal imaging approach can provide comprehensive and incremental
      information.>.

PMID- 30279794
TI  - Occasionally increased 18F-fluorodeoxyglucose uptake in apical hypertrophic
      cardiomyopathy with mid-ventricular obstruction.
AB  - We report on a 77-year-old man who was diagnosed with apical hypertrophic
      cardiomyopathy (HCM) with mid-ventricular obstruction. He had a cured hepatitis C
      infection. We detected occasionally increased 18F-fluorodeoxyglucose (18F-FDG)
      uptake on whole-body positron emission tomography (PET)/computed tomography (CT)
      performed to examine the involvement of bladder carcinoma. 18F-FDG-PET was
      restudied following specific preparation involving an 18-h low-carbohydrate diet
      and following 15-h fasting plus heparin pre-administration. Increased uptake of
      18F-FDG was observed reproducibly in the hypertrophic apical to mid left
      ventricular myocardium, with a maximum standardized uptake value of 6.2. In
      contrast, relatively lower 18F-FDG-uptake areas tended to match areas of late
      gadolinium enhancement on cardiac magnetic resonance (CMR). Histopathological
      examination of myocardial biopsy showed disarried hypertrophic myocytes with
      cellular infiltration. Increased uptake of 18F-FDG may reflect the phenomenon of
      increased glucose utilization in hypertrophied myocardium. The increasing
      clinical utility of whole-body PET/CT for evaluating malignancies may increase
      the detection of occasional abnormal 18F-FDG uptake in the heart. It is necessary
      to clarify that 18F-FDG myocardial PET in combination with CMR may provide a more
      detailed risk assessment in patients with HCM. <Learning objective: Increased 18F
      fluorodeoxyglucose (18F-FDG) uptake was occasionally found in the apex of the
      heart on whole-body positron emission tomography performed to evaluate bladder
      cancer involvement. Increased uptake of 18F-FDG was observed in the hypertrophic
      apical to mid left ventricular myocardium, while relatively lower 18F-FDG-uptake
      areas tended to match areas of late gadolinium enhancement.>.

PMID- 30279795
TI  - Replacement myocardial fibrosis at the site of late gadolinium enhancement on
      magnetic resonance imaging in a patient with diffuse cutaneous systemic
      sclerosis: An autopsy report.
AB  - Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a well
      known finding indicative of cardiac involvement in systemic sclerosis (SSc
      heart). However, few studies have reported the precise histopathology at the site
      of LGE. We present an autopsy report of a 51-year-old man diagnosed with diffuse
      cutaneous SSc according to a systematic diagnostic workup, including skin biopsy.
      CMR indicated left ventricular (LV) dilatation and broadly distributed
      subendocardial LGE in the LV walls. The patient was treated with
      methylprednisolone pulse therapy because of multiple episodes of ventricular
      tachycardia, whereas he subsequently died of left heart failure. An autopsy study
      revealed broad subendocardial replacement fibrosis, concomitant with the
      distribution of LGE on CMR, without inflammatory or edematous changes. Notably,
      myocardial fibrosis was evident around the intramural coronary arteries, although
      the arteries themselves were intact. These findings demonstrated that broad
      subendocardial LGE on CMR reflected replacement myocardial fibrosis in a patient
      with diffuse cutaneous SSc. These clinicopathological observations suggested that
      spasms in the intramyocardial arteries or the cardiac Raynaud's phenomenon may
      have provoked broad subendocardial fibrosis of the LV walls. <Learning objective:
      The present autopsy report pathologically validated the presence of broad
      myocardial fibrosis in the area of subendocardial late gadolinium enhancement
      (LGE) on cardiac magnetic resonance in a patient with systemic sclerosis (SSc).
      Lack of inflammatory changes along with intact coronary arteries suggested the
      involvement of intramural coronary spasm in the development of cardiac
      involvement in SSc. Such an LGE pattern may suggest end-stage cardiac involvement
      and portend a poor prognosis.>.

PMID- 30279796
TI  - "Slipstream technique"-New concept of intravascular ultrasound guided wiring
      technique with double lumen catheter in the treatment of coronary total
      occlusions.
AB  - Intravascular ultrasound (IVUS)-guided guidewire manipulation technique is often
      useful to cross the lesion of chronic total occlusion (CTO) antegradely and solve
      retrograde CTO failure cases. However, this technique is usually complex because
      we need many devices and it requires many steps. Some steps usually take time
      and/or sometimes create a large dissection space which cause the procedure to
      fail. To overcome a weakness in this technique, we introduce the new IVUS-guided
      wiring technique with double lumen catheter named "Slipstream technique" here.
      This technique is simple, easy, and associated with less injury. It will be
      helpful for penetrating into the true lumen from the subintimal space with a
      guidewire correctly and safely. <Learning objective: IVUS-guided wiring technique
      in the treatment of chronic total occlusion is usually complex. The key point of
      new IVUS-guided wiring technique is to put both the IVUS catheter and double
      lumen catheter on the same wire. This manner is simple. Moreover, it will
      increase the stability of double lumen catheter and be helpful to manipulate the
      second guidewire effectively.>.

PMID- 30279798
TI  - Percutaneous closure of a giant pulmonary arteriovenous malformation using
      multiple devices.
AB  - Percutaneous device closure is an established method to treat pulmonary
      arteriovenous malformation (PAVM). This report describes the case of a 23-year
      old man with hereditary hemorrhagic telangiectasia (HHT) presenting with dyspnea
      and hypoxia. The patient was found to have a giant left-sided PAVM. The patient
      underwent percutaneous closure of PAVM with multiple devices with a good outcome.
      At 12-month follow up, the patient was asymptomatic with near complete
      obliteration of the arteriovenous malformation. <Learning objective: This case
      demonstrates the feasibility and safety of using multiple devices to treat
      pulmonary arteriovenous malformation percutaneously. Good short-term (12-month)
      outcomes are demonstrated and there were no complications.>.

PMID- 30279797
TI  - A rare case of acute myocardial infarction with a non-specific symptom in a young
      female with systemic lupus erythematosus.
AB  - A 31-year-old female with an 18-year history of systemic lupus erythematosus
      (SLE) complained of epigastralgia and consulted the emergency outpatient
      department at our hospital. Her physical examination revealed tenderness at the
      scrobiculus cordis, which was a non-specific symptom of coronary heart disease
      (CHD). We ultimately gave a diagnosis of acute myocardial infarction based on
      coronary angiography and performed percutaneous coronary intervention. Although
      pre-interventional intravascular ultrasound demonstrated distinct atherosclerotic
      lesions in the coronary arteries, there were no atherosclerotic lesions in other
      systemic arteries. Although CHD in young SLE patients is a significant cause of
      morbidity and premature death, it tends to be misdiagnosed because their symptoms
      may be non-specific. In addition, this case highlights the fact that even SLE
      patients with no systemic atherosclerosis are at risk for the development of CHD.
      <Learning objective: Coronary heart disease (CHD) in young systemic lupus
      erythematosus (SLE) patients is a significant cause of morbidity and premature
      death, but it tends to be misdiagnosed because their symptoms may be non
      specific. Moreover, SLE patients are at risk for the development of CHD.>.

PMID- 30279799
TI  - Percutaneous isolation of left atrial appendage thrombus.
AB  - Most physicians regard left atrial appendage (LAA) thrombus as a contraindication
      for LAA occlusion due to risk of distal embolization which is a serious
      complication. Here we report a case of successfully implanted Amplazter cardiac
      plug without complication in elderly patients having LAA thrombus with recurrent
      embolic events despite oral anticoagulants for prevention of thromboembolic
      events. <Learning objective: LAA thrombus is not completely resolved in all cases
      and can be a potential source of stroke or embolization even during anti
      coagulation. We would like to share a case that suffered from 6 strokes or
      embolizations despite anti-coagulation, warfarin or non-vitamin K antagonist oral
      anti-coagulants due to incomplete resolution of LAA thrombus. In this clinical
      situation, we can suggest LAA occlusion to isolate thrombus from LA and prevent
      further stroke or embolization.>.

PMID- 30279800
TI  - A daytime normotensive patient with nocturnal hypoxia-induced hypertension and
      severe obstructive sleep apnea.
AB  - This is the case of a 60-year-old male. He had no past medical history at a
      regular medical check-up. According to findings at the regular medical check-up,
      he was obese (body mass index, 32.8 kg/m2), and had short neck, small jaw, and
      low soft palate; therefore, it was suspected that he may have sleep-disordered
      breathing. Blood pressure (BP) at the medical check-up was 121/80 mmHg, and the
      results of electrocardiogram and chest radiography were normal. Blood test data
      at the medical check-up indicated abnormality of lipid metabolism and
      hyperuricemia. No other abnormalities were found. It became clear that he became
      sleepy during daytime at an additional medical interview. Accordingly, he was
      diagnosed as having severe obstructive sleep apnea (OSA) with apnea-hypopnea
      index 65.3/h and arousal index 64.4/h by polysomnography. The oxygen-triggered
      nocturnal BP monitoring that was conducted at home around the same time indicated
      remarkable hypoxia-induced hypertension (Day 1: hypoxia-peak nocturnal BP 181/117
      mmHg, Day 2: hypoxia-peak nocturnal BP 204/137 mmHg). The patient recognized the
      risk of OSA by visualizing the hypoxia-induced hypertension; therefore,
      introduction of continuous positive airway pressure (CPAP) therapy for severe OSA
      was smooth. As the results of CPAP therapy, we could confirm disappearance of
      hypoxia-induced hypertension. <Learning objective: An office worker without
      cardiovascular disease was diagnosed as having severe obstructive sleep apnea.
      Remarkable hypoxia-induced nocturnal hypertension was identified by oxygen
      triggered blood pressure (BP) monitoring. It was considered that nocturnal
      hypertension, which was not able to be recorded by previous ambulatory blood
      pressure monitoring, was recorded by the oxygen-triggered BP monitoring method.>.

PMID- 30279801
TI  - An unusual cause of myocardial ischemia: Compression of a left internal mammary
      artery grafting to the left anterior descending artery by a pacemaker lead.
AB  - An 83-year-old patient, with prior history of coronary artery disease treated by
      coronary-artery bypass graft with left internal mammary artery (LIMA) to the left
      anterior descending artery (2001) and angioplasty of the right coronary artery
      (2012) and prior pacemaker through left subclavian vein (2014), was referred to
      coronary angiography for an anterior silent ischemia. It found no evolving lesion
      on the native coronary artery network (compared with 2012 review) but revealed an
      external compression of the LIMA bridge by the pacemaker lead. Conservative
      treatment was chosen rather than explantation and reimplantation of stimulus
      material or LIMA angioplasty. <Learning objective: This case highlights the
      interest for preferential use of the cephalic pathway in patients with left
      internal mammary bypass graft undergoing cardiac pacing.>.

PMID- 30279803
TI  - Streptococcus pyogenes meningitis and endocarditis in a patient with prosthetic
      mitral valve.
AB  - Streptococcus pyogenes is commonly found in cutaneous and pharyngeal infections,
      but rarely causes meningitis and endocarditis. We report a 77-year-old male with
      history of prosthetic mitral valve, presenting with meningitis and endocarditis
      secondary to S. pyogenes. We aim to raise awareness among clinicians of rare
      infectious etiology as the cause of endocarditis and meningitis, and importance
      of prompt diagnosis in ensuring success of medical treatment and long-term
      survival. <Learning objective: Main learning objectives are: (1) Rare sources of
      infection should be considered in setting of endocarditis and meningitis. (2) In
      high-risk patients, transesophageal echocardiogram is indicated although initial
      transthoracic echocardiogram may not show classic vegetation.>.

PMID- 30279802
TI  - Coronary artery stenting in acute coronary syndrome associated with giant cell
      arteritis.
AB  - Coronary vasculitis is a rare but devastating complication of giant cell
      arteritis, otherwise known as temporal arteritis. Originally named for its
      propensity to attack the superficial temporal arteries, it is now recognized that
      it commonly involves a number of medium and large arteries throughout the body.
      Here we describe two cases of giant cell arteritis affecting the coronary
      arteries, one discovered at post-mortem and one which was successfully treated
      with immunosuppressive therapy and drug-eluting coronary stents. <Learning
      objective: Giant cell arteritis is a large vessel vasculitis which commonly
      affects the superficial temporal, subclavian arteries, and aorta but in rare
      cases can involve the coronary arteries. In addition to standard corticosteroid
      therapy, drug-eluting stents may be useful in treating this rare but serious
      disease. Clinicians should both consider this condition in patients with atypical
      features of coronary artery disease and recognize drug-eluting stents as a
      potential effective therapy.>.

PMID- 30279804
TI  - A case of premature ventricular complexes/ventricular tachycardia from the left
      ventricular outflow tract successfully ablated from the distal great cardiac
      vein.
AB  - We experienced a 41-year-old male with premature ventricular
      complexes/ventricular tachycardia from the left coronary cusp and distal great
      cardiac vein of the left ventricular outflow tract successfully treated by
      radiofrequency catheter ablation utilizing a 3D mapping system
      (EnSiteNavX/VelocityTM Cardiac Mapping System, St. Jude Medical, St. Paul, MN,
      USA) without any complications. <Learning objective: The approach from the distal
      great cardiac vein should be considered as a potential approach and may be one of
      the effective strategies for ablation of left ventricular outflow tract-premature
      ventricular complexes/ventricular tachycardia (PVC/VTs). Radiofrequency catheter
      ablation of frequent PVC/VTs may improve the clinical status and cardiac
      function.>.

PMID- 30279805
TI  - Development of an iatrogenic aneurysm nine months after pacemaker implantation:
      Consideration of causes and treatment.
AB  - Careful technique is required in pacemaker implantation to avoid serious
      iatrogenic complications. A 70-year-old woman on an anticoagulant agent underwent
      pacemaker implantation. Nine months after implantation, a 35-mm pulsatile mass
      appeared just near the cranial edge of the generator. An iatrogenic
      pseudoaneurysm was suspected because ultrasonography showed communication with
      the blood stream through tiny artery. The resected mass proved to be a
      pseudoaneurysm. This was a rare case of iatrogenic delayed pseudoaneurysm
      appearing nine months later. It is essential to keep in mind the risk of
      pseudoaneurysm after pacemaker implantation, especially when the patient takes
      anticoagulant agents. <Learning objective: Iatrogenic delayed pseudoaneurysm
      might develop after pacemaker implantation. It is essential to avoid risk factors
      for a pseudoaneurysm after pacemaker implantation when the patient is taking
      anticoagulant agents and to keep in mind careful follow-up even after discharge.
      Prospective measures such as suspension of antithrombotic agents, minimizing
      puncture attempts, and wound compression are also important.>.

PMID- 30279806
TI  - Change in type of sleep-disordered breathing from predominant central to
      obstructive sleep apnea following coronary artery bypass grafting.
AB  - We report the case of a 67-year-old overweight man with reduced left ventricular
      ejection fraction (LVEF) due to myocardial infarction. He had an implantable
      cardioverter defibrillator (ICD) for frequent episodes of ventricular
      tachyarrhythmia and was initiated into adaptive-servo ventilation therapy for
      severe central sleep apnea (CSA), which was not suppressed by continuous positive
      airway pressure (CPAP). Since he still had several episodes of appropriate ICD
      therapies, coronary angiogram was performed, and severe three-vessel disease was
      found. He then underwent coronary artery bypass grafting (CABG). After CABG, his
      LVEF did not improve (from 29 to 25%); however, the B-type natriuretic peptide
      level decreased (from 560 to 330 pg/mL). Although the apnea-hypopnea index did
      not change (49.4 before and 55.1/h after CABG), his CSA converted to predominant
      obstructive sleep apnea accompanied by a shortening of the lung-to-finger
      circulation time (from 43 to 29 s) 2 weeks after CABG, which was completely
      suppressed by CPAP. <Learning objective: Central sleep apnea (CSA) can be
      alleviated by treatments for heart failure. However, limited data are available
      regarding resolution of CSA after coronary revascularization. We describe a case
      whose predominant CSA converted to obstructive sleep apnea after surgical
      coronary revascularization without any improvements in systolic function.
      Coronary revascularization can alleviate CSA possibly through altering congestive
      status and may unmask obstructive phenotype in patients with severe coronary
      artery disease.>.

PMID- 30279807
TI  - Contrast induced spinal myoclonus after percutaneous coronary intervention.
AB  - We present a case of a 77-year-old man diagnosed with contrast-induced spinal
      myoclonus following primary percutaneous coronary intervention. After being
      admitted with a diagnosis of anteroseptal myocardial infarction, he underwent
      primary percutaneous coronary intervention to the left anterior descending artery
      and was prescribed aspirin, clopidogrel, and intravenous heparin. The following
      day he developed non-intentional irregular jerky movements confined to the
      truncal area. In view of rhythmic jerking confined to muscles innervated by a
      restricted segment of the spinal cord, resistance to supra-spinal influences and
      voluntary action, and no preceding electroencephalography activity in the
      contralateral sensorimotor cortex, a diagnosis of spinal myoclonus was made.
      Spinal myoclonus is a rare entity in which myoclonic movements occur in muscles
      originating from few (segmental), or many adjacent spinal motor roots
      (propriospinal). Structural lesions are found in the majority of cases but the
      actual pathophysiology is still unknown. Contrast-induced spinal myoclonus is an
      even rarer phenomenon with few published reports. We describe postulated
      mechanisms and the management of this phenomenon. <Learning objective: Myoclonus
      is a jerky movement due to abrupt involuntary contractions involving agonist and
      antagonist muscles. Spinal myoclonus is a rare disorder where myoclonic movements
      occur in muscles originating from spinal motor roots. The cause is usually a
      structural lesion, but in rare cases it can be induced by contrast. A video of
      this rare phenomenon is available with this article and the proposed
      pathophysiological mechanisms and treatment are discussed.>.

PMID- 30279808
TI  - Successful revascularization of advanced coronary artery disease associated with
      pseudoxanthoma elasticum.
AB  - Pseudoxanthoma elasticum (PXE) is caused by loss-of-function mutations of the ATP
      binding cassette subfamily C member 6 gene. A 58-year-old man was diagnosed as
      having PXE based on typical findings in orbital and skin biopsies. Coronary
      computed tomography (CT) showed severe coronary stenosis in the proximal right
      coronary artery (RCA), and chronic total occlusion (CTO) of the mid left anterior
      descending coronary artery (LAD) with bridging collaterals. Coronary angiography
      revealed 99% stenosis in the RCA (#1) and CTO in the mid LAD (#7) with well
      developed collaterals from the LAD to the RCA. We performed percutaneous coronary
      intervention (PCI) and achieved complete revascularization. Intravascular
      ultrasound (IVUS) showed a superficial high echoic component around the vessels
      throughout the length of coronary arteries including non-stenotic regions. In the
      IVUS findings, the main cause of stenosis of the RCA lesion was large amounts of
      plaque, and the cause of the CTO in the LAD was coronary negative remodeling. In
      this case, coronary CT was clinically useful in the identification of ischemic
      heart disease. Since IVUS demonstrates variable findings in each coronary artery
      lesion and the morphologic characteristics might alter the strategy of PCI, IVUS
      should be performed at the time of PCI in PXE patients. <Learning objective:
      Pseudoxanthoma elasticum (PXE) has higher incidence of coronary artery disease
      (CAD). Coronary computed tomography is clinically useful in the identification of
      CAD in PXE patients. Intravascular ultrasound should be performed at the time of
      percutaneous coronary intervention in PXE patients, since the stenotic lesions of
      PXE have some morphological variations with a superficial high echoic
      component.>.

PMID- 30279809
TI  - Coronary artery stent dislodgement and aortic dissection in a patient with a
      severely calcified lesion in the proximal right coronary artery.
AB  - In atherosclerosis progression, calcium deposition may have an impact on the
      natural history of coronary atherosclerosis, and the amount of calcium may affect
      the success rate of percutaneous coronary intervention (PCI). Coronary stent
      dislodgement does not commonly occur in the modern PCI era; however, it may lead
      to fatal death. If it occurs, retrieval of a dislodged stent can be performed
      either surgically or percutaneously using a variety of retrieval techniques,
      including inflating a catheter balloon distal to the undeployed stent, twirling 2
      wires around the stent, a loop snare, or forceps. Here, we report a rare case
      that coronary artery stent dislodgement and aortic dissection simultaneously
      occurred during PCI for a severely calcified lesion in the proximal right
      coronary artery with shepherd's crook morphology. The situation was successfully
      rectified by using balloons to deploy the stent, as well as by applying an
      additional stent and minimizing the contrast used to treat aortic dissection.
      Learning objective: During percutaneous coronary intervention (PCI), stent
      dislodgement and aortic dissection are extremely rare, but life-threatening
      complications. In this rare case of simultaneous stent dislodgement in the
      coronary artery and aortic dissection during PCI for a severely calcified lesion
      in the right coronary artery with shepherd's crook morphology, the situation was
      successfully rectified by using balloons to retrieve and deploy the stent, as
      well as by applying an additional stent and minimizing the contrast used to treat
      aortic dissection.

PMID- 30279810
TI  - Successful early steroid and anticoagulant treatment for Loeffler's endocarditis
      related to eosinophilic granulomatosis with polyangiitis.
AB  - Loeffler's endocarditis is cardiac damage mediated by hypereosinophilia with a
      poor prognosis. A 45-year-old woman with Loeffler's endocarditis caused by
      eosinophilic granulomatosis with polyangiitis had hypereosinophilia (blood
      eosinophil count 32.4 * 109/L) and left ventricular systolic and diastolic
      dysfunction (left ventricular ejection fraction 45%, e' 5.1 cm/s).
      Echocardiography showed a left ventricular apical thrombus (32 * 30 mm). The
      cardiac magnetic resonance imaging scan showed a subacute thrombus (an iso
      intensity area on T1-weighted images and a high-intensity area on T2-weighted
      images). We administered prednisolone and anticoagulant immediately. The
      eosinophil count rapidly decreased. After 8 weeks, the thrombus gradually
      decreased in size (28 * 17 mm) and cardiac function improved (left ventricular
      ejection fraction 58%, e' 8 cm/s). On the follow-up cardiac magnetic resonance
      imaging scan, the thrombus gradually became organized (the high-intensity area on
      T2-weighted images became iso-intense). The subendocardial late gadolinium
      enhancement showed fibrosis only in a small part of the anterior left ventricular
      wall. Early steroids and optimal anticoagulant therapy may improve cardiac
      function and prognosis. Additionally, cardiac magnetic resonance imaging may be
      an important modality for diagnosis and follow-up. <Learning objective: In
      patients with Loeffler's endocarditis, early steroid treatment inhibits
      progression to the fibrotic stage and improves cardiac function. Anticoagulants
      decrease the size of the thrombus and also lead to improvement in left
      ventricular function. Cardiac magnetic resonance imaging can detect the phase of
      Loeffler's endocarditis by identifying fibrosis and characteristics of the
      thrombus. Therefore, cardiac magnetic resonance imaging may be an important
      modality for diagnosis and follow-up.>.

PMID- 30279811
TI  - Clinicopathological features of bi-ventricular cardiac intimal sarcoma-Report of
      an autopsy case.
AB  - We present the clinicopathological characteristics of primary cardiac intimal
      sarcoma which was widely spread throughout bi-ventricles. The patient had a wide
      range of clinical manifestations starting with left-sided heart failure then
      finally developing refractory right-sided heart failure during 44 months of
      follow-up. <Learning objective: The present clinicopathological characteristics
      with a wide spectrum of clinical features may provide a pivotal insight into
      understanding primary cardiac intimal sarcoma.>.

PMID- 30279812
TI  - Primary cardiac angiosarcoma. Histopathology imaging correlation.
AB  - We report a novel observation of a cardiac hemangioma possible transformation
      into cardiac angiosarcoma. This report should give a new insight on the
      pathogenesis of the tumor, always thought to have a de-novo genesis. We emphasize
      in our report the value of combining imaging modalities to examine the anatomic
      and metabolic properties of cardiac tumors providing a valuable tool for
      comprehensive assessment. <Learning objective: Assessment of cardiac tumors
      should combine different imaging modalities to examine the anatomic and metabolic
      properties of the lesions. We report a novel observation on cardiac angiosarcoma
      possible transformation from a cardiac hemangioma. This report should give a new
      insight into the pathogenesis of the tumor, always thought to have a de-novo
      genesis.>.

PMID- 30279813
TI  - Stent collapse caused by balloon occlusion and aspiration system in saphenous
      vein graft intervention.
AB  - We present the case of an 82-year-old male patient with unstable angina pectoris
      referred for percutaneous coronary intervention in the saphenous vein graft (SVG)
      to left circumflex coronary artery. An everolimus-eluting cobalt chrome stent was
      successfully deployed, using an embolic protection device with balloon occlusion
      and aspiration system. During the procedure of aspiration thrombectomy, the
      deployed stent unexpectedly collapsed. We re-dilated the collapsed stent using
      the same distal protection and aspiration system. However, the stent collapsed
      again during the aspiration procedure. As we could successfully re-dilate the
      collapsed stent using the same balloon occlusion and aspiration system after
      pulling the guide catheter out from the ostium of SVG, we concluded that the
      collapse of the stent was caused by the excess negative pressure generated by the
      distal occlusion and aspiration procedure under the completely wedged guide
      catheter into the ostium of SVG. We believe this is the first report of stent
      collapse due to excess negative pressure during aspiration thrombectomy.
      <Learning objective: Since the radial strength of coronary stents is high enough,
      deployed stent collapse is a rare complication. This case report describes a
      novel mechanism of stent collapse, which was caused by the excess negative
      pressure generated by the distal occlusion and aspiration procedure in saphenous
      vein graft intervention. To avoid this type of complication, in using distal
      protection devices, the side-hole guide catheter should be used, or the guide
      catheter should be carefully manipulated not to be wedged.>.

PMID- 30279814
TI  - Late rupture of artificial neochordae associated with hemolytic anemia.
AB  - A 63-year-old man, status post-mitral valve repair for severe mitral
      regurgitation secondary to ruptured chordae of the anterior leaflet, was admitted
      seven years after surgery because of a recent history of hematuria. A new apical
      pansystolic murmur was audible. Hemoglobin level was 5.7 g/dL. Results of other
      hematologic studies and a peripheral blood smear were indicative of mechanical
      hemolysis. Transesophageal echocardiography showed a high-velocity jet of mitral
      regurgitation that directly collided with the annuloplasty ring. At re-operation,
      one of the artificial neochordae to A2 and A3 segments was found to be disrupted.
      The mitral valve was replaced with a 33/31 mm On-X valve. Hemolytic anemia
      disappeared immediately after surgery. Although mitral valve repair with
      artificial neochodae has been shown to have long-term durability, it should be
      recognized that artificial neochordae may rupture a long time after mitral valve
      repair. Also, although hemolytic anemia is known as an early complication after
      mitral valve repair, it is worth knowing that hemolytic anemia may occur as a
      late complication after mitral valve repair. Continuous long-term monitoring of
      the patients after mitral valve repair is recommended. <Learning objectives:
      Artificial neochordae may at times rupture long period after mitral valve repair.
      Also, although hemolytic anemia is known as an early complication after mitral
      valve repair, it may occur as a complication due to late rupture of artificial
      neochordae. Continuous long-term monitoring of the patient after mitral valve
      repair is recommended.>.

PMID- 30279815
TI  - Congenital left main coronary artery atresia presenting as syncope and
      generalized seizure during exercise in a 13-year-old boy.
AB  - We report the case of a 13-year-old boy who, while running in a school gymnasium,
      experienced sudden syncope and seizure. CPR was started immediately, and an
      automated external defibrillator (AED) was attached, but shock was not induced.
      He was referred to our hospital for loss of consciousness and intermittent
      general tonic-clonic seizure. A 12-lead electrocardiogram showed normal sinus
      rhythm and no ST-T wave abnormalities. Echocardiography showed normal structural
      heart and normal cardiac function. On the second day of hospitalization, AED
      electrocardiogram showed complete atrioventricular (AV) block at syncope and
      seizure. After the patient recovered from this neurological state, we performed
      the treadmill exercise test, and it did not show ST-T wave abnormalities or AV
      block, and he did not complain of chest pain. Coronary angiography showed atresia
      of the left main trunk and the collateral vessel from the right coronary artery
      connected to the left coronary artery. He was diagnosed with congenital left main
      coronary artery atresia. We began administration of calcium antagonist and
      aspirin to prevent a coronary artery spasm and then performed a coronary artery
      bypass graft (CABG) to prevent sudden cardiac death. After CABG, he has had no
      syncope episodes at rest or during light exercise. <Learning objective: In
      pediatric patients, syncope during strenuous exercise should mandate exclusion of
      cardiac events, especially coronary artery anomalies. Coronary artery anomalies
      that could cause sudden cardiac death sometimes show no abnormalities at rest or
      even during exercise stress on 12-lead electrocardiogram. It is very important to
      suspect cardiogenic syncope during strenuous exercise.>.

PMID- 30279816
TI  - Transfemoral implantation of Edwards SAPIEN-XT(r) transcatheter heart valve in a
      degenerated tricuspid bioprosthesis.
AB  - We report on a percutaneous transcatheter valve-in-valve implantation (Edwards
      SAPIEN-XT(r)) (Edwards Lifesciences Corp., One Edwards Way Irvine, CA 92614) in a
      50-year-old i.v. drug user with a history of biological tricuspid valve
      replacement (Perimount 31 mm) (Edwards Lifesciences Corp., One Edwards Way
      Irvine, CA 92614) due to tricuspid valve endocarditis five years earlier. Re
      operation was considered unfavorable due to general and specific risk factors.
      The case was discussed by the heart team. Obviously, some type of valve
      replacement was required. Given the high risk of tricuspid valve re-operation in
      general and the specific risk factors of the patient (New York Heart Association
      functional class III, reduced right ventricular function, continued drug abuse,
      active hepatitis C and human immunodeficiency virus infection, suspected non
      compliance, unfavorable social background) the consensus was to attempt
      percutaneous transcatheter valve-in-valve implantation. Implantation of an
      Edwards-SAPIEN-XT(r) valve (Edwards Lifesciences Corp., One Edwards Way Irvine,
      CA 92614) in tricuspid position was successfully performed and the patient was
      transferred to the ward on day 2, completely free of symptoms. Pre-discharge
      echocadiographic control on day 6 again confirmed adequate position and regular
      function of the Edwards-SAPIEN-XT(r) valve (Edwards Lifesciences Corp., One
      Edwards Way Irvine, CA 92614) without any signs of regurgitation or stenosis.
      <Learning objective: Transcatheter valve-in-valve implantation in tricuspid
      position is feasible and offers a valuable therapeutic alternative in selected
      patients. Despite encouraging initial experience with transcatheter valve
      implantation in native or prosthetic tricuspid valves, further studies are needed
      to establish the clinical value of this technique.>.

PMID- 30279817
TI  - Focal right atrial tachycardia with three foci in a patient with polymyositis.
AB  - Cardiac involvement secondary to polymyositis is not infrequent. In addition, it
      sometimes presents various forms of arrhythmia, including atrial tachycardia
      (AT). A 72-year-old female who had 5-years history of polymyositis was referred
      to our clinic with symptomatic supraventricular tachycardia with 2:1
      atrioventricular conduction. Electrophysiological study revealed a total of three
      focal AT in right atrium with the origin of the basal right atrial appendage
      (AT1), coronary sinus ostium (AT2), and low lateral right atrium (AT3),
      respectively. Endocardial bipolar voltage mapping showed low voltage area in the
      limited area, partially overlapping with the focus of AT3. We finally terminated
      AT2 targeting an early fractionated potential and AT3 at early activation site
      with a support of flexibly-bended deflectable sheath while accidentally
      eliminating AT3 with the bumping of a catheter. With the additional applications,
      we completely eliminated all AT. AT were never provoked by any inductions with
      isoproterenol infusion. <Learning objective: Polymyositis is a broad-spectrum
      inflammatory disease which could involve myocardium, sometimes leading to the
      arrhythmogenicity. We should recognize the possibility of arrhythmia occurrence
      with multiple foci in patients with polymyositis when performing catheter
      ablation even if there were no obvious structural and functional heart
      abnormality.>.

PMID- 30279818
TI  - Cardiac hydatid cyst of the right ventricle: Severe localization.
AB  - A 24-year-old male was admitted for syncope and epigastric pain and fever.
      Biological examination showed leukocytosis and marked eosinophilia, the brain
      computed tomography (CT) was normal. The echocardiography revealed a voluminous
      mass in the free wall of the right ventricle compressing the right cavities
      without communication confirmed with thoracic CT. Hydatid serology was positive.
      Early and urgent surgery was decided. The postoperative period was uneventful and
      the patient was discharged home on albendazole. Hydatid cyst is an endemic
      parasitic infection in cattle-breading countries, and migration has played a
      significant role to expand this infection worldwide. Cardiac hydatidosis is rare
      (0.5-2%) in comparison with hydatidosis of the liver (65%) and lung (25%). The
      right ventricle location is even rarer, 10% versus 60% for the left ventricle,
      and can cause fatal complications such as anaphylactic shock, dissemination, and
      pulmonary embolism. <Learning objective: Report of a rare occurrence of right
      ventricle hydatid cyst, and underlining the atypical clinical presentation and
      difficulties of treatment.>.

PMID- 30279819
TI  - Untreated cardiac sarcoidosis with active inflammation: Severe left ventricular
      dysfunction and ventricular wall thinning in three years.
AB  - A 74-year-old female was admitted for the treatment of complete atrioventricular
      block. Echocardiography showed thickening of interventricular septum and a slight
      thinning in the basal region with normal left ventricular (LV) function. She was
      clinically diagnosed with cardiac sarcoidosis accompanied by active inflammation
      from the findings of blood test, nuclear scanning, and magnetic resonance
      imaging. After pacemaker implantation, we recommended corticosteroid therapy,
      which she refused for the fear of side effects. Three years later, she was re
      admitted to our hospital due to heart failure. Echocardiography showed severe LV
      systolic dysfunction and dilatation with wall thinning. Even though we started
      corticosteroid therapy and continued it for one year, LV function was not
      improved. In patients with cardiac sarcoidosis accompanied by active
      inflammation, LV dysfunction, and dilatation may rapidly progress. Early
      diagnosis and treatment with corticosteroid may be important to preserve cardiac
      function. <Learning objective: Left ventricular (LV) dysfunction in patients with
      cardiac sarcoidosis accompanied by active inflammation may rapidly progress in a
      short period. Corticosteroid therapy is demonstrated to improve the long-term
      clinical outcome, however, it may not be effective once LV function is worsened
      with wall thinning. Early diagnosis and treatment with corticosteroid may be
      important to preserve cardiac function in patients with cardiac sarcoidosis
      accompanied by active inflammation.>.

PMID- 30279820
TI  - Successful treatment of a massive pulmonary embolism using rivaroxaban in a
      patient with antithrombin III deficiency.
AB  - We report a case of acute massive pulmonary embolism in a patient with
      antithrombin III deficiency. The patient was treated with rivaroxaban. The
      patient responded well to the therapy, and contrast-enhanced computed tomography
      showed nearly complete disappearance of the pulmonary embolism. Patients with low
      antithrombin III activity may have resistance to heparin therapy, leading to
      insufficient anticoagulation during the acute phase of thromboembolism. This case
      suggests that direct oral anticoagulants, such as rivaroxaban, may be effective
      first-line agents for treating venous thromboembolism in patients with
      antithrombin III deficiency. <Learning objective: Recently, direct oral
      anticoagulants represent a novel treatment option for venous thromboembolism with
      several practical advantages over conventional therapy. Antithrombin-III
      deficiency may lead to insufficient anticoagulation during the acute phase of
      thromboembolism. The present case suggests that rivaroxaban is a direct Factor Xa
      inhibitor and does not require cofactors such as antithrombin-III, thus it is
      suitable for anticoagulation therapy in patients with low antithrombin-III
      activity.>.

PMID- 30279821
TI  - Late perforation of a passively fixated pacemaker lead through the right
      ventricle. A report and review of literature.
AB  - Lead perforation is one of the serious complications associated with cardiac
      pacemakers and implantable cardiac defibrillators. Late perforations - occurring
      more than one month after placement - are exceedingly rare and are usually more
      associated with actively fixed leads rather than passively fixed tined leads. We
      present a case of blunt ended tined lead perforation after 4 months of
      implantation managed by a two-step hybrid minimally invasive approach consisting
      of mini-thoracotomy and lead tip transection, followed by trans-venous lead
      extraction. <Learning objective: Late perforation of a pacemaker lead (occurring
      more than one month after placement) is an exceedingly rare complication and is
      usually more associated with actively fixed leads rather than passively fixed
      tined leads. We describe management of a blunt-ended tined lead perforation by a
      two-step hybrid minimally invasive approach consisting of mini-thoracotomy and
      lead tip transection, followed by trans-venous lead extraction.>.

PMID- 30279822
TI  - Acute right to left shunt-Combination of tricuspid valve endocarditis, Chiari
      network, and ostium secundum atrial septal defect.
AB  - A 72-year-old Tongan female was admitted to our facility with dyspnea and
      refractory hypoxia. She became febrile and blood cultures were positive for
      Enterococcus faecalis. Transesophageal echocardiography was performed showing two
      large vegetations on the tricuspid valve causing severe regurgitation. The
      tricuspid regurgitant jet with the assistance of a large Chiari network was being
      directed across an ostium secundum atrial septal defect. This clinical scenario
      represented an unusual cause of acute right to left shunt explaining the
      patient's refractory hypoxia. <Learning objective: Acute right to left intra
      cardiac shunts occur rarely however should be considered in any patient with
      acute onset refractory hypoxia.>.

PMID- 30279823
TI  - Out-of-hospital cardiac arrest related to coronary arterial spasm in three
      elderly patients with no obstructive coronary artery disease.
AB  - Coronary spastic angina (CSA) is relatively more common in young people than in
      elderly people. Here, we present three cases of elderly male patients who
      experienced out-of-hospital cardiac arrest (OHCA) likely due to coronary spasm
      induced ventricular fibrillation (Vf) from 2013 to 2016. After defibrillation,
      emergency coronary arteriography demonstrated severe coronary vasospasm that
      resolved following intracoronary infusion of nitroglycerin in the right coronary
      arteries in all three patients, with no organic obstructive lesion in the
      coronary arteries after nitroglycerin infusion. Case 1 was a 74-year-old patient
      with a past history of unstable angina and no organic obstructive lesion on
      coronary arteriography. He was administered oral amlodipine, isosorbide
      mononitrate, and nicorandil. He survived an OHCA and underwent implantable
      cardioverter defibrillator (ICD) implantation on day 57. Case 2 was a 71-year-old
      patient without prior CSA, who suddenly lost consciousness during a break after
      tennis. Vf was reversed to sinus rhythm by defibrillation in the ambulance. He
      died of multi-organ failure on day 7. Case 3 was a 66-year-old patient diagnosed
      with multi-vessel CSA by coronary arteriography with acetylcholine provocation
      test. He survived an OHCA associated with inferior acute myocardial infarction,
      rejected ICD implantation, and has not had a chest pain attack or syncope since
      discharge. <Learning objective: This article reports a case series of out-of
      hospital cardiac arrest (OHCA) likely due to coronary spastic angina (CSA) in the
      presence of non-obstructive coronary artery disease in elderly patients. Although
      CSA is associated with an increased risk of OHCA, little is known regarding
      clinical risk factors, the effectiveness of implanted defibrillators for the
      secondary prevention of cardiac arrest, or the long-term prognosis of elderly CSA
      patients who survive OHCA.>.

PMID- 30279824
TI  - Angle-tipped guidewire-induced vascular perforation at branch of superior
      thoracic artery during sheath insertion: Case report.
AB  - An 84-year-old woman was admitted to our hospital because of congestive heart
      failure, rapid atrial fibrillation, and ischemic heart disease. Percutaneous
      coronary intervention (PCI) via the left radial artery was performed, and a stent
      was deployed successfully into left anterior descending coronary artery (LAD).
      She got into shock state one hour after PCI. Chest X-ray and computed tomography
      scan revealed increase of soft tissue around the left axilla and implied the
      existence of hematoma. Hemoglobin level decreased from 13.3 g/dL to 8.2 g/dL and
      hemorrhagic shock was suspected. Angiography of the left axillary artery
      demonstrated contrast extravasation, and selective angiography using a micro
      catheter identified bleeding from a branch of the superior thoracic artery.
      Hemostasis was performed successfully by embolization using a gelatin sponge, and
      improvement of the general condition was obtained. Aberration of 0.025-in. angle
      tipped guidewire was considered to induce arterial perforation during sheath
      insertion. <Learning objective: Guidewire-induced perforation is a known rare and
      sometimes fatal complication of percutaneous interventional procedures. The
      incidence of angiographic-evident peripheral artery perforation has been reported
      to be 0.9%. In particular, a guidewire advanced into a small branch artery can
      potentially cause perforation. This risk suggests that clinicians should use
      caution when manipulating a guidewire during sheath insertion.>.

PMID- 30279825
TI  - Thrombolytic treatment for acute prosthetic valve thrombosis: Is it better than
      surgery?
AB  - Prosthetic valve thrombosis (PVT) is a rare but often lethal complication of
      valve replacement. Despite advances in surgical techniques, surgical mortality
      remains high and emergent cardiac surgery is not widely available. Herein, we
      present the case of an acute PVT successfully treated with thrombolytic therapy.
      A 48-year-old female presented to the emergency department with acute onset of
      shortness of breath. Her medical history was remarkable for mitral valve
      replacement at the age of 42 years. Her symptoms began 4 h before, when she
      suddenly presented severe resting dyspnea. At arrival she showed pulmonary edema
      and hemodynamic instability. Echocardiography showed a prosthetic mitral valve
      stuck in a semi-closed position with a gradient of 39 mm Hg. Treatment was
      started with alteplase and the patient presented marked clinical improvement in
      subsequent hours. Recent evidence suggests that thrombolysis could be elected as
      the first choice of treatment in patients with left-side PVT because of the
      effectiveness, safety profile, availability, and low cost. This case illustrates
      the importance of prompt diagnosis and treatment and proposes thrombolytic
      therapy for PVT as an option at least as efficient as and far more accessible
      than surgery. <Learning objective: This case illustrates the importance of prompt
      diagnosis of prosthetic valve thrombosis (PVT) and proposes thrombolytic therapy
      for PVT as an option at least as efficient as and far more accessible than
      surgery.>.

PMID- 30279826
TI  - Percutaneous closure of an iatrogenic ventricular septal defect following
      transcatheter aortic valve implantation.
AB  - Transcatheter aortic valve implantation (TAVI) has been increasingly used in
      symptomatic patients with severe aortic stenosis who are at high risk for
      conventional open heart surgery. However, it might be associated with serious
      complications. We report a case with an iatrogenic ventricular septal defect as a
      rare complication following TAVI procedure. <Learning objective: To highlight a
      rare complication of iatrogenic ventricular septal defect (VSD) following
      transcatheter aortic valve implantation procedure and its treatment with
      percutaneous interventional VSD closure.>.

PMID- 30279827
TI  - Metastatic obliterating mass of right ventricular cavity: A report of case and
      echocardiographic features.
AB  - We present the case of a 63-year-old man with a history of non-small cell lung
      carcinoma (NSCLC) and systemic chemotherapy who suffered from progressive
      shortness of breath and peripheral edema. Transthoracic echocardiography showed a
      huge non-homogenous mass nearly completely filling the dilated right ventricle.
      The border of mass was not differentiable from the right ventricular myocardium.
      The findings of echocardiographic study were highly suggestive for cardiac
      metastasis. Computed tomography and positron emission computed tomography
      confirmed the presumed diagnosis. Lung cancer is one of the most common primary
      tumors of cardiac metastasis and NSCLC accounts for about 85% of all lung
      cancers. Lymphatic spread or direct invasion usually involves the pericardium or
      epicardium. However, metastasis to the myocardium and endocardium is extremely
      rare. The huge size, location, direct invasion to myocardium and
      echocardiographic features of this cardiac mass have made it a unique case for
      presentation. <Learning objective: Despite the versatility and high accuracy of
      cardiac computed tomography (CT), magnetic resonance imaging, and 18
      fluorodeoxyglucose positron emission CT, echocardiography remains the modality of
      choice for the initial evaluation and follow-up examinations of cardiac masses.
      Although echocardiography is limited in regard to tissue characterization and
      characterization of extra cardiac structures, this image modality is widely
      accessible without relevant side effects, and allows the assessment of
      hemodynamic consequences of cardiac masses involving the myocardium valves, or
      pericardium.>.

PMID- 30279828
TI  - Acute ischemic stroke what is hidden behind?
AB  - Acute aortic dissection (AAD) is a rare and potentially fatal disease. The
      classic presentation is sudden and severe pain in the chest, back, or abdomen,
      described as tearing or ripping pain radiating to the interscapular region.
      Cerebral ischemic complications occur in 18-30% of aortic dissections and
      patients may present to the emergency department (ED) with isolated focal
      neurology and no chest pain. In AAD patients, presenting with stroke and
      subsequently thrombolized, a 71% mortality rate has been reported in patients
      receiving recombinant tissue plasminogen activator (r-TPA). We present a case of
      a 58-year-old male patient that presented to ED with sudden onset of headache and
      left-sided hemiparesis, computed tomography (CT) demonstrated an ischemic stroke
      of the right middle cerebral artery. When the question of whether to start r-TPA
      or mechanical thrombectomy was discussed, a cardiac point-of-care ultrasound was
      performed in ED and showed a type A aortic dissection; immediately a CT aortic
      angiogram was performed and confirmed the diagnosis. The patient was taken to
      theater and had a favorable outcome. <Learning objective: Acute aortic dissection
      (AAD) may present as acute ischemic stroke with no chest pain. In patients with
      acute ischemic stroke with an unclear etiology point-of-care ultrasound (POCUS),
      cardiac, and aortic ultrasound are important rapidly to diagnose AAD and avoid
      the deleterious effect of thrombolysis. This case supports the feasibility of
      emergency physicians performing POCUS assessments for AAD.>.

PMID- 30279829
TI  - Mitochondrial deformity confined to a single cardiomyocyte in human
      endomyocardial biopsy specimens: Report of 4 cases.
AB  - During electron microscopic examination of 156 consecutive human endomyocardial
      biopsy specimens, we found marked mitochondrial deformity within a single
      cardiomyocyte in each of 4 specimens. The deformed mitochondria were unevenly
      distributed, but the deformities were confined to the one cardiomyocyte. Those
      affected cardiomyocytes were accompanied by nonspecific degenerative changes such
      as nuclear hypertrophy and/or rarefaction of the myofibrils. Mitochondria in all
      other cells within the specimens appeared normal. Such an abnormality has never
      been reported to date. Each of the four cases was diagnosed with a different
      ailment: post-myocarditis, dilated cardiomyopathy, amyloidosis, and tachycardia
      induced heart failure. However, all four cases were accompanied by left
      ventricular systolic dysfunction at biopsy. The very limited mitochondrial
      deformation may thus reflect a type of degenerative change that accompanies heart
      failure. <Learning objective: A marked mitochondrial deformity must have been
      overlooked to date, which is confined to a single cardiomyocyte in an
      endomyocardial biopsy specimen. Its etiology is still unknown but may reflect a
      type of degenerative change that accompanies heart failure.>.

PMID- 30279830
TI  - Acute compartment syndrome: A rare but important complication of transradial
      cardiac catheterization.
AB  - The transradial approach has become the gold-standard for coronary angiography.
      It is better tolerated by patients, associated with less bleeding, earlier post
      procedure mobilization, and reduced mortality in patients with myocardial
      infarction. Given the hand's dual arterial supply and extensive collateral
      circulation, the risk of serious functional injury after radial catheterization
      is essentially reduced to zero. However, even a small amount of bleeding in the
      volar compartment can lead to compartment syndrome (CS) and permanent
      neurovascular injury. The purpose of this paper is to describe our experience
      with an unusual case of late-onset acute CS following transradial coronary
      angiography, and to summarize the available literature on this topic. <Learning
      objective: The transradial approach has become the gold-standard for coronary
      angiography. However, in rare cases, this approach may be associated with
      bleeding and acute compartment syndrome. Patients on anticoagulants, and those
      who have severe atherosclerosis appear to be at increased risk of this
      complication. The diagnosis relies upon clinician awareness and vigilance, and
      affected patients require early decompressive fasciotomy to prevent permanent
      neurovascular injury.>.

PMID- 30279831
TI  - An autopsy case of aortic root rupture with thin porcelain aorta during balloon
      expandable transcatheter aortic valve implantation.
AB  - A 92-year-old woman was transferred to our institute due to drug-resistant heart
      failure from severe aortic stenosis. She seemed to be a candidate for
      transcatheter aortic valve implantation (TAVI) because of her frailty and
      porcelain aorta. There were no severe calcified nodules in the left-ventricular
      outflow tract area. Because three-dimensional computed tomography analysis showed
      that her basal annulus area was 419 mm2, a 26-mm SAPIEN XT (Edwards Lifesciences,
      Irvine, CA, USA) was selected for implantation. After deployment of the valve
      with 10% reduced volume, aortic root rupture occurred and her blood pressure fell
      due to acute cardiac tamponade. Emergent cardiac pericardial fenestration was
      done and drained blood was continuously returned to the circulation through
      percutaneous cardiopulmonary bypass. Despite strenuous efforts to save her life,
      she died 13 h after the event. An autopsy revealed a thin porcelain aorta and
      aortic root rupture with a fragile aortic wall. <Learning objective: Porcelain
      aorta is known to be a risk factor for perioperative stroke during surgical
      aortic valve replacement, and TAVI could be chosen for a treatment strategy in
      those cases. We present a case of aortic root rupture caused by unusually fragile
      aortic wall during TAVI and the lesson from the autopsy results.>.

PMID- 30279832
TI  - Evaluation and medical therapy for coronary endothelial dysfunction induced by
      sirolimus-eluting stent in patient with an atherosclerotic lesion of the left
      main coronary artery: Case report.
AB  - Sirolimus-eluting stents (SES), especially those deployed at distal sites, cause
      more coronary vasospasm and endothelial dysfunction in the chronic phase compared
      to bare-metal stents (BMS). In comparison, endothelial dysfunction is less
      frequently induced by the Biolimus-A9 eluting stent (BES). A 75-year-old man with
      effort-induced angina pectoris previously underwent a total of three SES
      implantations in the left anterior descending coronary artery (LAD) and right
      coronary artery (RCA) in 2010 and 2011. He was referred to our hospital for the
      management of chest discomfort at rest in August 2014. We diagnosed this patient
      with coronary spastic angina (CSA) and coronary endothelial dysfunction (CED)
      induced by the SES, together with an atherosclerotic lesion in the left main
      coronary artery (LMCA). Adequate medication for CSA and CED and intervention for
      the atherosclerotic lesion contributed to improvement of vascular function and
      disappearance of his symptoms. <Learning objective: The frequency of endothelial
      dysfunction induced by Biolimus-A9 eluting stents (BES) is less than that induced
      by Sirolimus-eluting stents (SES), although all drug-eluting stents are more
      likely to cause coronary vasospasm and endothelial dysfunction in the chronic
      phase, especially at distal deployment sites, as compared to bare-metal stents
      (BMS). Adequate medication for coronary spastic angina (CSA) and endothelial
      dysfunction, and interventions for atherosclerotic lesions are useful for
      improving vascular function and cardiac symptoms.>.

PMID- 30279833
TI  - A case of upper extremity deep vein thrombosis with long-term patency using
      pharmaco-mechanical catheter-directed thrombolysis in the acute phase.
AB  - Although upper-extremity deep vein thrombosis (UEDVT) is considered rare, its
      prevalence appears to be increasing, and this may be related to expanding
      indications for catheter-based interventions. In contrast, few cases have been
      reported related to strenuous exercise, especially in healthy young adults with
      thoracic outlet syndrome (Paget-Schroetter syndrome). In contrast to lower
      extremity DVT, optimal treatment strategies for UEDVT have not been robustly
      studied. In this report, we describe a 56-year-old man with primary UEDVT
      presenting with left arm swelling, paresthesia, and visible collateral veins
      around the shoulder. Venography revealed thrombotic occlusion of the left
      subclavian vein. Emergent pharmaco-mechanical catheter-directed thrombolysis
      (PCDT) was performed, and his left subclavian vein was recanalized. A novel oral
      anticoagulant was initiated to prevent reclosure. The patient's symptoms subsided
      without major bleeding complications and at six months, he has no disability for
      daily activities. Follow-up ultrasonography revealed almost complete patency of
      the left subclavian vein, after which anticoagulation therapy was terminated. We
      discuss the role of PCDT in the management of primary UEDVT from the perspective
      of efficacy and contribution to quality of life. <Learning objective: UEDVT is
      relatively rare and has not been examined as extensively as lower-extremity DVT.
      Nonetheless, patients may have a variety of unpleasant symptoms that
      substantially decrease quality of life. Pharmaco-mechanical catheter-directed
      thrombolysis may be effective to reduce clot burden and mitigate the risk of post
      thrombotic syndrome. Although there is no current consensus about exact
      indications for UEDVT patients, the procedure may be more useful than the
      standard anticoagulant therapy.>.

PMID- 30279834
TI  - Successful angioplasty with intravascular ultrasound and optical frequency domain
      imaging guidance for tandem intramural hematoma caused by coronary artery spasm.
AB  - A 39-year-old woman with no coronary risk factors was admitted due to repetitive
      morning chest pain. Coronary angiography revealed subtotal occlusion of the
      distal obtuse marginal branch that was not recanalized by intracoronary
      nitroglycerin administration. Intravascular ultrasound and optical frequency
      domain imaging showed tandem intramural hematomas in the culprit vessel. We
      performed cutting balloon angioplasty successfully with dual intracoronary
      imaging modality guidance. The 4-month follow-up angiography revealed favorable
      vascular healing and the provocation test induced multiple spasms, including in
      the culprit vessel, by intracoronary acetylcholine administration. <Learning
      objective: Coronary artery spasm could be the cause of tandem intramural
      hematomas with clinical presentation of acute coronary syndrome. Angioplasty with
      dual imaging modality guidance is a useful option for diagnosing and treating for
      intramural hematoma.>.

PMID- 30279835
TI  - A remarkable case of late-onset biatrial bacterial endocarditis of the Gore HELEX
      septal occluder.
AB  - The HELEX septal occluder (W.L. Gore & Associates, Newark, DE, USA) is a popular
      closure device for patent foramen ovale (PFO) and secundum atrial septal defect
      (ASD). Composed of a versatile polymer and a wire frame, it has been used for
      nearly a decade. A 50-year-old African American man with a PFO repaired 5 years
      previously with the HELEX was admitted to our hospital with methicillin-resistant
      Staphylococcus aureus bacteremia. A transesophageal echocardiogram demonstrated
      large mobile vegetations on the left and right atrial aspects of the occluder.
      Cardiothoracic surgery was consulted for removal of the vegetations and device,
      but hesitated owing to concurrent foot osteomyelitis and concern for re-infection
      of a potential replacement device. The patient was persistently bacteremic, his
      course complicated by septic pulmonary and cerebral emboli, but eventually
      cleared his infection on antibiotic therapy. Seventy days since admission, the
      patient was discharged to a rehabilitation facility. The case illustrates that
      infection is possible years after PFO/ASD closure despite a theoretical
      neoendothelialization within 6 months of implantation. Furthermore, it
      accentuates the success of timely and aggressive medical treatment, thereby
      averting high-risk open cardiac surgery. <Learning objective: The Gore HELEX
      atrial septal occluder was designed to minimize post-implantation infection.
      However, our case illustrates that the device can be vulnerable to infection even
      years after placement. Additionally, treatment success with non-operative
      management underpins the value of swift and aggressive antimicrobial therapy.>.

PMID- 30279836
TI  - Dislodged stent after stent reverse controlled antegrade and retrograde
      subintimal tracking (CART) - Is stent reverse CART a necessary tool or an
      unnecessary evil?
AB  - We report a case of stent reverse controlled antegrade and retrograde subintimal
      tracking (CART) in left anterior descending artery (LAD) chronic total occlusion.
      Reverse CART is the method used to make a connection between the retrograde wire
      and the antegrade true lumen by using a balloon to dilate the antegrade space and
      pushing the retrograde wire into this space. We successfully crossed the septal
      channel from right coronary to the LAD, and proceeded to reverse CART, which was
      unsuccessful. After demonstrating that both the retrograde and antegrade wires
      were in the same subintimal space by intravascular ultrasound (IVUS), we placed
      the distal stent edge at the connection point of the wires and deployed the
      stent. We could easily wire the stent lumen with the retrograde conquest 9 g
      wire. Afterwards we tried to push the retrograde corsair microcatheter through
      the CTO and into the antegrade guiding, but unfortunately, the retrograde corsair
      could not pass into the antegrade guiding and was stuck just outside the
      antegrade guiding ostium. At this point IVUS showed that the stent had been
      dislodged from the LAD and pushed into the aorta just outside the left main by
      the retrograde corsair because the retrograde wire passed into the stent lumen
      through a distal side strut opening and not through the true distal end of the
      stent. Due to unstable hemodynamics we had to remove the retrograde system and
      this led to stent embolism. The case illustrates stent dislodgement after stent
      reverse CART and stresses the importance of using IVUS to check fully the
      retrograde wire path before pushing the corsair. We discuss the role of stent
      reverse CART in the contemporary reverse CART era and conclude that it should be
      relegated to the very last resort after trying transit balloon technique. We
      conclude that stent reverse CART is mostly an unnecessary evil. <Learning
      objective: The case illustrates the dangers of stent reverse controlled antegrade
      and retrograde subintimal tracking (CART) and discusses the alternative options
      to stent reverse CART, as well as how to perform stent reverse CART safely with
      the use of intravascular ultrasound both before stenting and after stenting to
      ensure correct wire passage through the stent.>.

PMID- 30279837
TI  - A case of aortic valve laceration after balloon aortic valvuloplasty with
      morphological features.
AB  - A 71-year-old man suffered from congestive heart failure due to severe aortic
      stenosis. We performed balloon aortic valvuloplasty (BAV) as a bridge to
      transcatheter aortic valve replacement using transesophageal echocardiogram (TEE)
      by the retrograde approach. Balloon dilatation was carefully performed using an
      18 mm balloon. After balloon dilation, TEE showed right coronary cusp (RCC)
      laceration and severe aortic regurgitation. We discontinued the procedure despite
      the incomplete result. Aortic valve laceration is a rare complication considered
      to be mainly caused by the use of large balloon or by balloon slipping. In the
      present case, TEE showed that the commissure of RCC fused strongly with both the
      other cusps by thick calcification, and the center of RCC had a spotty low echoic
      area with soft tissue. The force of the balloon dilatation concentrated to soft
      tissue area and lacerated the center of RCC. We verified the finding in the
      operative specimen. When performing BAV, we should pay attention to the
      morphology of the aortic valve using TEE to avoid aortic valve laceration as a
      fatal complication. <Learning objective: Aortic valve laceration is a rare
      complication. The main reasons of laceration are considered to be a large size
      balloon or balloon slipping. The morphology of the aortic valve may cause the
      laceration as observed in the present case. It is important to pay attention to
      the morphology of the aortic valve by preoperative transesophageal
      echocardiogram.>.

PMID- 30279838
TI  - Transcatheter aortic valve implantation in a patient with aplastic anemia.
AB  - Aplastic anemia is a syndrome involving pancytopenia caused by bone marrow
      insufficiency. Pancytopenia increases the surgical risk of bleeding and
      infection. Here, we report a successful transcatheter aortic valve implantation
      (TAVI) in a patient with aplastic anemia. The patient was a 76-year-old woman who
      was admitted to our hospital with syncope. Laboratory testing showed
      pancytopenia, and echocardiography revealed severe aortic valve stenosis.
      Although the log.EuroSCORE and STS Score were not overly high, because of the
      presence of pancytopenia, surgical aortic valve replacement was considered too
      high risk, making her a candidate for TAVI. In this case, the patient's
      pancytopenia was so severe that even TAVI without preparation was considered high
      risk. In light of this, we carried out a two-day preoperative administration of
      granulocyte colony-stimulating factor and transfused packed red blood cells and
      platelet concentrates. TAVI was performed via the left femoral artery using the
      cut-down procedure under general anesthesia. The postoperative course was
      uneventful, and she was discharged on the sixth postoperative day. With adequate
      preoperative preparation, TAVI may be performed safely in high-risk patients with
      hematologic disorders. <Learning objective: Transcatheter aortic valve
      implantation (TAVI) is widely performed for aortic stenosis patients at high
      surgical risk. Although patients with severe pancytopenia can be candidates for
      TAVI, severe pancytopenia may increase the surgical risk even for TAVI. To reduce
      the risk, adequate preparations before the procedure are required. Here, we
      report the preoperative preparation before TAVI that lowered the surgical risk in
      a patient with severe pancytopenia.>.

PMID- 30279839
TI  - Progressive spontaneous coronary artery dissection secondary to fibromuscular
      dysplasia requiring mechanical circulatory support.
AB  - Spontaneous coronary artery dissection (SCAD) usually appears as an acute
      coronary syndrome with good prognosis. We present the case of a 39-year-old woman
      with progressive SCAD secondary to fibromuscular dysplasia with catastrophic
      course. The patient required several mechanical circulatory support systems
      including a left ventricular assist device (CentriMag(r), Thoratec, Pleasanton,
      CA, USA) as bridge to recovery. <Learning objective: The beneficial use of
      mechanical circulatory support devices as a bridge to recovery or heart
      transplant in the setting of refractory cardiogenic shock in spontaneous coronary
      artery dissection.>.

PMID- 30279840
TI  - Incorrect Holter-ECG analysis caused by the pacemaker delivering small high
      frequency currents for thoracic impedance measurement.
AB  - In an 86-year-old woman who had been treated for sick sinus syndrome, the small
      high-frequency current delivered by pacemaker in order to measure the minutes
      ventilation for utilizing the rate-response mode was transiently over-sensed on
      the Holter electrocardiogram. Although her pacing system was working
      appropriately, the numbers of the paced beats on the automatic Holter analysis
      were undercounted (from >60% to <5%) during the over-sensing periods because
      these currents were recognized as multiple pacing spikes. Physicians need to pay
      attention to such multiple pacing spike markers, because these can be a cause of
      unreliable results of the Holter analysis. <Learning objective: Paying attention
      to multiple pacing spike markers on Holter electrocardiogram is clinically
      important in patients treated by a rate-response pacemaker. This is because (1)
      this does not imply the malfunction of the pacemaker system, and (2) results from
      automatic Holter analysis would not be reliable during the period when these
      multiple pacing markers were recorded.>.

PMID- 30279841
TI  - Dog-bone inflation to salvage and redeploy a deformed, dislodged expandable stent
      in the external iliac artery.
AB  - A 64-year-old man with a history of right external iliac artery stenosis after
      stenting with a self-expandable stent was admitted for repetitive in-stent
      restenosis (ISR). To treat ISR, we selected a balloon expandable stent (BES) that
      was prepared with negative suction before being inserted into the sheath. BES
      dislodged when the stent balloon was incompletely inflated and was simultaneously
      deformed in a funnel shape. When BES was retrieved using a short noncompliant
      balloon, it dislodged again because of an imbalanced proximal inflation of the
      balloon. We finally retrieved BES using a long noncompliant balloon and deployed
      it with dog-bone inflation without any additional devices. <Learning objective:
      To report an easy method for retrieving and redeploying a deformed, dislodged
      stent without using an additional device. Retrieving a relatively large
      peripheral stent that becomes deformed and dislodged is difficult and may require
      surgery. Balloon catheter retrieval is a useful strategy to salvage and redeploy
      the dislodged stent. However, a large size short noncompliant balloon catheter
      had the risk for dislodging the retrieved deformed stent again. To retrieve and
      salvage a deformed and dislodged stent, a long balloon and dog-bone inflation may
      be useful.>.

PMID- 30279842
TI  - Three-year follow-up optical coherence tomography of under-expanded drug-eluting
      stent in-stent restenosis treated with ABSORB bioresorbable vascular scaffold
      following ultra-high pressure pre-dilatation.
AB  - The management of in-stent restenosis continues to be a common challenge in
      modern interventional cardiology. Drug-eluting stents have emerged to be an
      effective treatment following bare-metal stent in-stent restenosis as compared
      with drug-coated balloon angioplasty and repeat bare-metal stenting. The addition
      of another metallic layer is however undesirable and may limit further treatment
      options. In the last few years, everolimus-eluting bioresorbable vascular
      scaffolds have become available in treating native coronary artery disease with
      complete hydrolysis into water and carbon dioxide within 3-5 years. To exploit
      this property, we successfully used it to manage a case of drug-eluting stent in
      stent restenosis from a previously under-expanded stent as demonstrated in this
      case. Small registry series have also recently been published supporting
      favorable outcomes with this approach. To the best of our knowledge, this case
      has the longest optical coherence tomography follow-up beyond 3 years. <Learning
      objective: The dedicated dual-layer OPN NC balloon (Schwager Medica, Winterthur,
      Switzerland) could be used in the under-expanded metallic stent that is not
      overcome by conventional non-compliant balloons as demonstrated in our case. The
      application of bioresorbable vascular scaffold in drug-eluting stent in-stent
      restenosis has satisfactory medium- to long-term clinical outcome. The 3-year
      follow-up intracoronary study demonstrated complete tissue coverage of the
      scaffold. Complete bioresorption of the scaffold, by hydrolysis into carbon
      dioxide and water, takes approximately 3-5 years, thus avoiding another layer of
      metallic cage.>.

PMID- 30279843
TI  - Superior vena cava syndrome complicated with acute pulmonary thromboembolism in a
      patient with lung cancer.
AB  - Thrombosis involving the subclavian vein and superior vena cava is relatively
      common, especially in cancer patients. Edema of the arms and head is a well-known
      clinical consequence of this thrombosis. The intrinsic risk of pulmonary embolism
      has not been reported previously. Herein, we describe the case of a 63-year-old
      male patient with extensive stage small cell lung cancer who developed superior
      vena cava syndrome. Pulmonary thromboembolism was complicated after receiving
      systemic chemotherapy and localized radiotherapy. <Learning objective: Superior
      vena cava (SVC) syndrome may pose a significant risk factor of pulmonary
      thromboembolism. Although SVC syndrome and pulmonary thromboembolism may have
      similar comorbidities, pulmonary thromboembolism might occur after treatment of
      SVC syndrome. Possible mechanisms may be related to tumor debris and
      hypercoagulable central vein thrombosis. Physicians must be vigilant with
      patients whom have dyspnea after treatment of SVC syndrome. Computed tomography
      angiography may help make an early diagnosis if clinical suspicion is made.>.

PMID- 30279844
TI  - Support with a twist: New approaches in CTOs and complex lesions.
AB  - One-third of patients undergoing coronary angiography have coronary chronic total
      occlusions (CTOs) with the incidence increasing with age. Successful
      recanalization of a CTO is associated with a reduction in the future need for
      coronary artery bypass graft surgery (CABG), improvement in left ventricular
      function, and angina status as well as long-term survival. Success rates for
      treating CTOs with conventional techniques have remained unchanged over time
      averaging 65%-70% in experienced hands, well below the success rates for non
      occlusive coronary lesions. The antegrade approach is utilized in standard
      balloon angioplasty. Modification of this technique has been used with an
      anchoring balloon to more successfully open up CTOs. We describe a new device
      that in addition to allowing increased support, also centers one in the lumen for
      both coronary and peripheral intervention. <Learning objective: Coronary total
      occlusions (CTOs) are the biggest reason patients are sent for coronary bypass
      when multi-vessel coronary disease is found. In most peripheral artery disease
      (PAD) patients, at least one peripheral vessel is 100% occluded. Current device
      designs have improved success rates in treating coronary and peripheral CTOs. The
      CrossLockTM catheter centers the lumen and gives better support to a chronically
      occluded vessel. The reader will find this device helpful in treating coronary
      and peripheral complex disease.>.

PMID- 30279845
TI  - Percutaneous pulmonary debanding for an infant complicated by spontaneously
      closing muscular ventricular septal defect: A case report and in vitro study.
AB  - Pulmonary artery banding (PAB) is a standard operation for various congenital
      heart defects complicated by pulmonary hypertension (PH) and judged unsuitable
      for primary intracardiac repair. We report successful percutaneous pulmonary
      artery debanding in a baby complicated by muscular ventricular septal defect
      (VSD), that was initially large and multiple, but closed spontaneously later. The
      5-month-old boy was referred to our hospital on day 3, diagnosed as having aortic
      coarctation (CoA), with multiple muscular VSDs and severe PH. On day 6, he
      underwent CoA repair and PAB using expanded polytetrafluoroethylene (ePTFE),
      while the muscular VSDs were left open. We planned percutaneous pulmonary
      debanding at the age of 5 months, as the muscular VSDs had become small. After
      dilation with a Mustang(r) (Boston Scientific, Marlborough, Massachusetts, United
      State) balloon (12 mm diameter) there was a persistent waist indicating a
      residual narrowing. Use of an extra-high pressure balloon, Conquest(r) (Medicon,
      Osaka, Japan) balloon of the same size, completely eliminated the waist. In in
      vitro experiments, the Mustang(r) partially tore the ePTFE, while a Conquest(r)
      of the same diameter completely opened the band. The mechanism of debanding was
      tearing of the ePTFE by the knot of the suture thread. Percutaneous pulmonary
      debanding to avoid unnecessary surgery is feasible in such a patient if the VSD
      becomes small. <Learning objective: Use of an extra-high pressure balloon,
      Conquest(r) (Medicon, Osaka, Japan) balloon could open the pulmonary artery
      banding made of expanded polytetrafluoroethylene (ePTFE). The mechanism of
      debanding was tearing of the ePTFE by the knot of the suture thread. Percutaneous
      pulmonary debanding to avoid unnecessary surgery is feasible in such a patient if
      the ventricular septal defect (VSD) becomes small.>.

PMID- 30279846
TI  - Clinical efficacy of a stent-in-stent procedure for stent fracture in a narrowing
      anastomosis of femoral-popliteal bypass represented repetitive acute limb
      ischemia.
AB  - A 72-year-old male with sudden onset pain and coldness in his left lower limb was
      referred to our hospital. An emergency angiography of the lower limbs
      demonstrated the cause of acute limb ischemia as a subsequent acute
      thromboembolism at the site of a narrowing anastomosis of femoral-popliteal
      bypass (FPB). In particular, the site of the narrowing anastomosis had already
      been fixed using a nitinol stent 4 years previously. We confirmed that the severe
      stent fracture resulted from misalignment. After local lysis therapy, we decided
      to deploy another nitinol stent to in-stent restenosis (ISR) lesion of the stent
      fracture. Final angiography confirmed full patency in FPB without flow delay.
      Additionally, to maintain the patency of arterial flow, we prescribed aspirin and
      warfarin. After 2 years of operation, his follow-up ankle-brachial pressure index
      on the left side remained 0.86 and no ischemic leg pain was observed to date.
      Stent-in-stent procedure using another nitinol stent for ISR treatment for the
      narrowing anastomosis in FPB indicated feasible and effective results. <Learning
      objective: Endovascular intervention for acute limb ischemia (ALI) is one of the
      most challenging cases. Physicians often come up against a problem as no-flow
      phenomenon after revascularization. Local lysis therapy has established its own
      position in ALI treatment. However, the effectiveness of various interventional
      treatments for ALI has not been clarified. This report highlights the potential
      of a combination of local lysis and intervention in achieving good outcomes in
      represented repetitive ALI.>.

PMID- 30279847
TI  - Retrograde parallel wire technique using a dual lumen catheter can be useful for
      percutaneous coronary intervention with chronic total occlusion.
AB  - The patient was a 61-year-old male with chronic total occlusion (CTO) of the
      right coronary artery (RCA). We performed percutaneous coronary intervention
      (PCI) to RCA-CTO with the bidirectional approach via the left anterior descending
      artery. In retrograde approach, the first wire entered the false lumen at the
      segment of severe stenosis of the CTO distal site. We performed parallel wire
      technique using a dual lumen catheter to avoid branch loss and succeeded to get
      the proximal true lumen through the second wire. When the first wire enters the
      false lumen, continued advancement of this wire easily should be avoided as it
      can collapse the true lumen and make reentry difficult. On top of that, in
      retrograde approach, it is difficult to perform parallel wire technique without
      using a dual lumen catheter. This case reveals that retrograde parallel wire
      technique using a dual lumen catheter is an extremely effective strategy to treat
      CTO. <Learning objective: The dual lumen catheter is one of the most helpful
      devices. However, in the field of percutaneous coronary intervention for chronic
      total occlusion (CTO-PCI), especially retrograde approach, the usage of them has
      not been established. Retrograde parallel wire technique using a dual lumen
      catheter may be useful for CTO-PCI.>.

PMID- 30279848
TI  - Transcatheter bicuspid aortic valve replacement in Turner syndrome: A unique
      experience of interventional cardiologist.
AB  - A 69-year-old short-statured Turner syndrome (TS) patient with a history of
      poliomyelitis in childhood and moderate bicuspid aortic stenosis (BAS) reported
      worsening dyspnea and fatigue over six months. A repeat transthoracic
      echocardiogram revealed progression to severe aortic stenosis with dilated
      ascending aorta (AA). As part of the work-up for aortic valve replacement, the
      patient underwent cardiac catheterization, which revealed a severely calcified AV
      with an area of 0.5 sq. cm and a mean gradient of 37 mmHg. On coronary
      angiography, there was 70% stenosis of the proximal left anterior descending
      artery (LAD). Due to poor rehabilitation potential, she was deemed high-risk for
      surgical aortic valve replacement. A recommendation for transcatheter aortic
      valve replacement (TAVR) with stenting of the proximal LAD was made. Dilated AA
      was managed conservatively with serial noninvasive imaging. The patient underwent
      TAVR with Edwards-Sapien valve (23 mm S3) and stenting of proximal LAD. The
      procedure was successful without complications. To our knowledge, our patient is
      the first case of TAVR in BAS with aortopathy in TS. <Learning objective:
      Therapeutically, transcatheter aortic valve replacement is an off-label
      indication for bicuspid aortic stenosis. In real-life practice, many of these
      patients are poor surgical candidates and demand careful and judicious decision
      making in the presence of diverse clinical scenarios. In such circumstances, a
      multidisciplinary approach with shared decision-making is required to recommend
      best possible therapeutic solution in the presence of limited data.>.

PMID- 30279849
TI  - Formation of a left atrial thrombus during percutaneous mitral valve edge-to-edge
      repair induced by acute reduction of mitral regurgitation.
AB  - Percutaneous mitral valve repair (PMVR) using the MitraClip system (Abbott,
      Abbott Park, IL, USA) is an innovative method allowing treatment of mitral
      regurgitation (MR) for patients that are not accessible by conventional
      operation. Thrombogenicity in the left atrium (LA) in general is increased in the
      presence of atrial fibrillation and mitral valve disease. We observed in a
      patient who underwent PMVR an acute change in thrombogenicity in the LA with
      thrombus formation in the left atrial appendix (LAA) immediately after clip
      placement. Thrombus formation occurred under verified therapeutic anticoagulation
      using unfractionated heparin. To our knowledge this is the first patient with
      documented acute and solid intra-interventional thrombus formation. The
      observation implies that acute reduction of mitral valve regurgitation and
      changes in hemodynamics within the LA enhances the risk of thrombus formation.
      <Learning objective: Percutaneous mitral valve repair is associated with acute
      changes in the thrombogenicity within the left atrium despite adequate
      periinterventional anticoagulation.>.

PMID- 30279850
TI  - Conservatively treated coronary malperfusion associated with acute type A
      dissection before aortic root replacement.
AB  - Coronary malperfusion associated with aortic dissection usually requires
      aggressive surgical treatment or catheter revascularization. Here, we report a
      case of conservatively treated coronary malperfusion associated with acute type A
      dissection before aortic root replacement. An 81-year-old woman was rushed to our
      hospital in a state of circulatory shock after developing chest pain. She was
      severely hypotensive on admission, and the electrocardiogram (ECG) revealed
      anterior and lateral ST elevation. However, the initial fluid resuscitation
      increased her blood pressure to a normal level, and the ischemic ECG changes
      disappeared in about 20 min. ECG-gated cardiac multidetector computed tomography
      showed a type A aortic dissection complicated with left main trunk dissection. A
      primary entry tear was located 5 mm below the left coronary ostium. The patient
      successfully underwent composite graft replacement of the aortic root in a stable
      hemodynamic condition. <Learning objective: Emergency clinicians should be aware
      that coronary malperfusion associated with aortic dissection can be improved by
      conservative management in some cases. Electrocardiogram-gated cardiac
      multidetector computed tomography is a useful tool for the diagnosis and clinical
      management of this condition.>.

PMID- 30279851
TI  - An enlarging pacemaker pocket: A case report of a plasmablastic lymphoma arising
      as a primary tumor around a cardiac pacemaker and systematic literature review of
      various malignancies arising at the pacemaker pocket.
AB  - To date, there have been limited reports of oncogenesis occurring within
      pacemaker pockets. We report the case of a 100-year-old male who presented to the
      emergency department complaining of expansion of his pacemaker pocket over the
      period of 8 days. Dissection of the pacemaker pocket and pathological analysis of
      tissue samples revealed plasmablastic lymphoma, a subset of diffuse large B-cell
      lymphoma, commonly seen in immunocompromised elderly patients. This is the first
      known reported case of plasmablastic lymphoma occurring within a pacemaker
      pocket. <Learning objective: We describe the first case of a plasmablastic
      lymphoma arising as a primary tumor around a pacemaker site. A thorough
      literature review of primary tumors arising around pacemakers is provided. As the
      life expectancy of our population increases, the amount of time that pacemakers
      are in place increases as well. Therefore, we discuss several mechanisms that may
      have led to the oncogenicty of pacemakers, as well as the role of titanium in
      carcinogenesis.>.

PMID- 30279852
TI  - The effect of pannus and weight gain in mitral stenosis after mitral ring
      annuloplasty.
AB  - Pannus formation is a known complication of valve replacement surgery. However,
      few cases describe pannus formation in the mitral position, and they are mostly
      associated with prosthetic valves rather than only annuloplasty. We describe the
      case of a 62-year-old woman who first underwent reductive annuloplasty using a
      Carpentier-Edwards 28 mm ring prosthesis in 2009 that performed well on regular
      follow-up for 5 years. In 2014, the patient presented with significant weight
      gain, shortness of breath (New York Heart Association functional class III) and
      signs of severe mitral stenosis. Echocardiography demonstrated the formation of a
      pannus and increased pressure gradients. Removal of the ring prosthesis and
      pannus-like fibrotic tissue was performed. The native valve was left in place as
      it had supple leaflets and performed well once properly debrided. The patient
      remained well throughout a 24-month follow-up. <Learning objective: This case
      report presents a rare phenomenon that will help familiarize readers with this
      complication type. Pannus formation of this type is rarely documented and
      encountered.>.

PMID- 30279853
TI  - Acute myocardial infarction in dextrocardia - A diagnostic and therapeutic
      challenge. Can dextrocardia be a risk factor?
AB  - Acute myocardial infarction in dextrocardia may present several challenges either
      in electrocardiographic diagnosis or coronary intervention or both, due to
      abnormal location of the heart, mirror images o the aorta and its branches, and
      abnormal coronary origin and orientation. Also, dextrocardia as a risk factor for
      coronary artery disease is less well established. We report the case of a young
      patient with dextrocardia and situs inversus without any risk factor who
      presented with acute extensive anterior wall myocardial infarction diagnosed
      after lead reversal and who successfully underwent coronary intervention using
      "double inversion technique". <Learning objective: Dextrocardia imposes a big
      challenge in diagnosing acute myocardial infarction on electrocardiography (ECG).
      Both limb and precordial leads should be reversed to reveal all ECG changes. Also
      because of the unfamiliar anatomy of coronaries and great vessels, double
      inversion technique is useful during the intervention. It is not well-established
      whether dextrocardia can be a risk factor for myocardial infarction.>.

PMID- 30279854
TI  - Successful combined intravenous and subcutaneous immunoglobulin treatment for
      intractable protein-losing enteropathy in a patient long after Fontan-type
      operation.
AB  - A 20-year-old patient, who had double outlet right ventricle, mitral atresia,
      pulmonary atresia, and bilateral superior vena cava and underwent successful
      lateral tunnel total cavo-pulmonary connection at 6 years old, presented with
      frequent watery diarrhea, general malaise, and tetany. He was known to have
      intractable protein-losing enteropathy (PLE) from 7 years of age that was
      resistant to various treatments. To keep hemodynamics stable, he required
      intravenous albumin infusion every day. Fontan fenestration partially improved
      his condition and allowed to stop albumin infusion, however still he showed muddy
      stool and cachexia with low serum albumin <20 g/L and immunoglobulin <3 g/L.
      Because of serious risk of infection, we placed him on regular subcutaneous
      immunoglobulin supplementation with rescue intravenous immunoglobulin that
      improved his PLE within a month and allowed him to be discharged. This case
      illustrates that immunoglobulin supplementation can be one of the choices of
      treatment for intractable PLE. <Learning objective: Combined subcutaneous and
      intravenous immunoglobulin infusion therapy can be one of the choices of
      treatment for intractable protein-losing enteropathy that does not respond to
      multiple medications.>.

PMID- 30279855
TI  - Aortic coarctation endarteritis: The importance of a systematic echocardiographic
      study.
AB  - Aortic coarctation determines a favorable anatomical condition for the
      development of endocarditis-endarteritis due to the presence of an alteration in
      blood flow dynamics that favors the appearance of endothelial damage and the
      adhesion of microorganisms. At present, endarteritis of aortic coarctation is a
      rare entity due to early detection and surgical treatment of patient carriers of
      aortic coarctation. We present a case of a patient affected with a previously
      unknown aortic coarctation, who developed infective endarteritis with secondary
      formation of mycotic aneurysm. The echocardiography techniques proved determinant
      in establishing the diagnosis of aortic coarctation, as well as the associated
      infectious complications. <Learning objectives: In this paper we show an
      infrequent case of vascular infection nowadays, as a complication of a congenital
      heart disease. Physical examination and echocardiography were clues for an early
      diagnosis, and should emphasize the performance of a complete echocardiography
      that includes the suprasternal view.>.

PMID- 30279856
TI  - Narrowing of the QRS complex, elimination of late gadolinium enhancement and
      remarkable reverse remodeling achieved by optimal medical treatment in non
      ischemic dilated cardiomyopathy.
AB  - A 67-year-old woman presented with exertional dyspnea. An electrocardiogram
      showed complete left bundle branch block. Cardiac magnetic resonance imaging
      revealed left ventricular (LV) dilatation with reduced ejection fraction, no
      evidence of myocardial ischemia and late gadolinium enhancement (LGE) in the
      inferior LV wall. She was diagnosed with decompensated heart failure (HF)
      secondary to non-ischemic dilated cardiomyopathy. Narrowing of the QRS complex,
      disappearance of LGE, and remarkable LV reverse remodeling along with improvement
      in HF symptoms were achieved by combination therapy with angiotensin II receptor
      blocker, beta-blocker, and mineralocorticoid receptor antagonist. This case
      highlights the role of triple-blockade therapy in the treatment of HF. <Learning
      objective: Complete left bundle branch block and late gadolinium enhancement
      usually represent irreversible damage of myocardial tissue, and are related to
      left ventricular (LV) remodeling. However, the clinical course of the present
      case indicated that optimal medical therapies including sufficient amount of
      renin-angiotensin-aldosterone inhibition and beta-adrenergic blockade can improve
      ventricular conduction delay and myocardial tissue injury, and consequent
      remarkable LV reverse remodeling.>.

PMID- 30279857
TI  - A unique case of ST-elevation myocardial infarction related to very late stent
      thrombosis.
AB  - A 67-year-old man was transferred to our hospital because of anterior ST
      elevation myocardial infarction (STEMI). He had a history of a sirolimus-eluting
      stent implantation from the left main to the left anterior descending coronary
      artery (LAD) 9 years before and had undergone laparoscopic prostatectomy 8 days
      before in the setting of discontinuation of dual antiplatelet therapy. Emergent
      coronary angiography showed total occlusion in the distal LAD that was
      successfully treated by aspiration alone. Optical coherence tomography (OCT)
      showed no vulnerable lesion from the occluded lesion to the proximal LAD. OCT
      demonstrated that the thrombus attached to floating struts at the left main
      bifurcation and non-apposed struts at the left coronary ostium partly protruding
      to aorta, while the other struts were covered and well-apposed. Based on OCT
      findings, this case of STEMI was thought to be caused by distal embolism of a
      thrombus that formed at the stent site before it evolved into total occlusion.
      <Learning objective: We demonstrated how optical coherence tomography can be
      essential in revealing the underlying pathology. The patient showed an unusual
      manifestation of ST-elevation myocardial infarction caused by distal embolism of
      a thrombus that formed at the sirolimus-eluting stent due to dual antiplatelet
      therapy discontinuation during perioperative period. Optical coherence tomography
      revealed very late stent thrombosis at the left coronary ostium and could
      elucidate the underlying mechanism.>.

PMID- 30279858
TI  - Late complications of an atrial septal occluder provoked by anticoagulant
      therapy.
AB  - Late complications of an atrial septal occluder device (ASO) are rare but may be
      serious. We report a case with extensive hemopericardium five years after ASO
      implantation most likely triggered by anticoagulant therapy. Although not
      surgically confirmed, indirect clues for erosion of the atrial wall by the device
      were the exclusion of other etiologies, lack of recurrence after pericardial
      drainage and withdrawal of anticoagulants. In addition, multimodality imaging
      using echocardiography, computed tomography, and cardiac magnetic resonance
      imaging were helpful to elucidate this unusual cause. Initiation of anticoagulant
      treatment in patients with an ASO should be carefully balanced and may warrant
      more frequent echocardiographic follow-up. <Learning objective: Late
      complications of an atrial septal occlude device (ASO) are rare. Initiation of
      anticoagulant therapy in patients with an ASO may lead to late hemopericardium,
      suggesting that more frequent echocardiographic follow-up is warranted.>.

PMID- 30279859
TI  - Catheter-induced aortocoronary dissection at the ostium of anomalous left
      coronary artery during percutaneous coronary intervention for acute inferior
      myocardial infarction.
AB  - We report a case of catheter-induced aortocoronary dissection at the ostium of
      anomalous left coronary artery (LCA) during percutaneous coronary intervention
      (PCI) for acute inferior myocardial infarction (MI). Urgent coronary angiography
      revealed the culprit lesion of MI was the proximal segment of the right coronary
      artery (RCA). The anomalous LCA arose from the right sinus of Valsalva the same
      as the RCA. Catheter-induced aortocoronary dissection at the ostium of RCA was
      extended to the ostium of anomalous LCA by contrast injection. The patient fell
      into hemodynamic collapse due to acute occlusion of the anomalous LCA. The
      patient underwent successful bailout stenting at the ostium of anomalous LCA
      under percutaneous cardiopulmonary support (PCPS). He was weaned from PCPS system
      five days after PCI and was discharged. This is the first report about bailout
      procedure for catheter-induced aortocoronary dissection at the ostium of
      anomalous LCA. <Learning objective: We present a case of catheter-induced
      aortocoronary dissection at the ostium of anomalous left coronary artery in a
      patient with acute inferior myocardial infarction. Anomalous origin of the
      coronary artery arising from the opposite sinus of Valsalva is a rare congenital
      anomaly. Aortocoronary dissection is also a rare but well-known complication
      during cardiac catheterization. Precise information on anatomy of anomalous
      coronary arteries is essential for percutaneous coronary intervention and
      attention should be paid to the potential risk of complications.>.

PMID- 30279860
TI  - Nature's balancing act: Infective endocarditis of pulmonary valve with
      ventricular septal defect in fifth decade; a rare and unusual presentation.
AB  - It is unusual for a moderate-size ventricular septal defect (VSD) to remain
      asymptomatic and complication-free until the age of 45 years. Similarly,
      infective endocarditis of anatomically normal pulmonary valve is also rare. Here
      we report a case in which nature created a protection for VSD, i.e. right
      ventricular outflow tract (RVOT) obstruction, which led to a complication, i.e.
      pulmonary valve endocarditis. A 45-year-old sick-looking man presented in medical
      emergency with fever and progressively increasing breathlessness for the previous
      2 weeks. He had no significant past history. The patient was febrile and on
      cardiovascular (CVS) examination, ejection systolic murmur in left upper
      parasternal region was heard, suggesting a diagnosis of infective endocarditis.
      Echocardiography revealed subaortic VSD of 1.2 cm size with left to right shunt.
      There was moderator band hypertrophy in sub-infundibular right ventricle (RVOT
      obstruction) creating obstruction to blood flow, thus preventing development of
      pulmonary artery hypertension. There were two large vegetations (4 * 3 mm) on
      each leaflet of pulmonary valve. High speed turbulent jet of blood generated from
      right ventricle obstruction was striking the pulmonary valve leaflets which led
      to injury and subsequent development of infective endocarditis of pulmonary
      valve. The patient improved on intravenous antibiotics. The plan was to give 6
      weeks of antibiotics followed by surgical closure of VSD and resection of
      moderator band. <Learning objective: It is rare for a moderate size ventricular
      septal defect to remain asymptomatic and complication-free until the age of 45
      years. Sometimes nature creates a barrier in the form of moderator band
      hypertrophy in sub infundibular right ventricle i.e. RVOT obstruction, leading to
      obstruction to blood flow and preventing development of pulmonary hypertension.>.

PMID- 30279861
TI  - Treatment of hypochloremia with acetazolamide in an advanced heart failure
      patient and importance of monitoring urinary electrolytes.
AB  - Chloride was recently recognized to play an important role in the pathophysiology
      of heart failure (HF). Chloride manipulation, including the use of acetazolamide,
      may be a requisite therapeutic target in HF treatment. An 87-year-old male
      patient with advanced HF and hypertrophic cardiomyopathy was admitted to the
      hospital due to hypochloremia (94 mEq/L) and hyponatremia (134 mEq/L) under
      diuretic treatment with azosemide, spironolactone, and tolvaptan. On admission,
      HF-related signs of overhydration were lacking, but B-type natriuretic peptide
      was moderately elevated. The etiology of the hypochloremia/natremia state was
      depletion of both electrolytes based on serum analysis and spot urinary
      concentrations. Immediately after admission, acetazolamide (500 mg/d) was
      prescribed to correct the hypochloremia in parallel with cessation of the
      preceding administration of azosemide and spironolactone, and tapering off of the
      tolvaptan over 7 days. Under treatment, both serum chloride and sodium
      concentrations recovered to normal (108 mEq/L and 148 mEq/L, respectively), and
      the serum potassium concentration decreased from 3.9 mEq/L to 2.4 mEq/L. Urinary
      concentrations of sodium and potassium increased from 18 mEq/L to 31 mEq/L and
      from 19 mEq/L to 51.5 mEq/L respectively, in concordance with the changes in
      serum concentrations, but the chloride concentration decreased from 18 mEq/L to
      12 mEq/L, opposite the changes in the serum concentration. <Learning objective:
      The present case confirms that the classic drug acetazolamide, although rarely
      used now for HF treatment, is a potent "chloride-regaining" or "chloride
      retaining diuretic" with concomitant activity to reduce serum potassium.
      Additionally, this case study highlights the importance of monitoring both serum
      and urinary electrolyte concentrations to determine the electrolyte disturbance
      and efficacy of diuretic treatment through analytic evaluation of changes in the
      serum electrolytes and their tubular reabsorption in the kidney.>.

PMID- 30279863
TI  - The novel use of retrograde CTO PCI techniques as a rescue strategy for an acute
      right coronary artery occlusion due to iatrogenic dissection.
AB  - Coronary artery dissection is a known complication of percutaneous coronary
      intervention (PCI). Such dissections are often treated by antegrade PCI. When
      antegrade PCI fails, the options become limited to conservative management or
      coronary artery bypass grafting (CABG). CABG comes with its own risks, and
      conservative management can result in a potentially larger infarct. Here we
      present a novel use of retrograde chronic total occlusion (CTO) PCI techniques to
      treat an iatrogenic, type D dissection of the right coronary artery in a young
      male with an acute coronary syndrome. Reentrance of the true lumen by standard
      antegrade approaches failed. The rescue strategy using a retrograde CTO PCI
      approach not only had advantages over surgery and conservative management, but
      also over antegrade PCI. A soft wire, designed for collaterals, was used to
      "surf" the dissection and reach the antegrade guiding catheter. Thus, the true
      lumen could be used. This novel approach provided the advantages both of
      preserving major side branches, which are often lost with antegrade PCI
      approaches, and of not unnecessarily puncturing the dissection membrane.
      <Learning objective: Extensive iatrogenic coronary artery dissections not
      amenable to antegrade PCI are typically managed conservatively or by CABG. A
      novel, bail-out strategy using retrograde CTO PCI techniques provided another
      treatment strategy. A soft wire, designed for collaterals, was used to "surf" the
      dissection and reach the antegrade guiding catheter. This method has the great
      advantage of preserving major side branches, which are often lost with antegrade
      PCI approaches.>.

PMID- 30279862
TI  - Unilateral cardiogenic pulmonary edema.
AB  - A 45-year-old man presented with fatigue for the previous two days. Because of
      severe hypoxemia and chest radiograph showing severe consolidation only in the
      right lung field, he was admitted to a near-by district hospital under the
      diagnosis of acute pneumonia. Since his respiratory condition rapidly
      deteriorated, he was transferred to our hospital. The diagnosis of unilateral
      cardiogenic pulmonary edema was made based upon the echocardiographic examination
      which showed severe mitral regurgitation secondary to chordal rupture of the
      posterior mitral valve leaflet (P2). After successful intensive medical treatment
      with diuretics and extracorporeal membrane oxygenation, mitral valve repair was
      performed with quadrangular resection of the posterior mitral leaflet (P2) and
      insertion of 28 mm Cosgrove ring. It is important to recognize acute and severe
      mitral regurgitation as a main cause of unilateral cardiogenic pulmonary edema.
      Prompt differentiation from acute pneumonia is critical to save lives of the
      patients. <Learning objective: Unilateral cardiogenic pulmonary edema is an
      unusual condition and may often be misdiagnosed as acute pneumonia, resulting in
      an increased risk of mortality. A correct differentiation from pneumonia is
      critical to save lives of the patients. It is important to recognize acute and
      severe mitral regurgitation as a main cause of this unusual condition.>.

PMID- 30279864
TI  - Time course of restenosis with "black hole" on intravascular ultrasound after
      implantation of platinum-chromium everolimus-eluting stent: Assessment using
      optical frequency-domain imaging.
AB  - Management of in-stent restenosis (ISR) remains challenging even in the drug
      eluting stent era. We report the case of a Japanese female with repeated ISR
      after primary percutaneous coronary intervention (PCI) for acute coronary
      syndrome. We observed ISR tissue with "black hole" on intravascular ultrasound,
      which appeared to be heterogeneous tissue on optical frequency-domain imaging
      (OFDI). Paclitaxel-coated balloon dilatation of the ISR lesion with "black hole"
      was ineffective. The morphological assessment of ISR tissue using OFDI might be
      important to treat ISR lesions by PCI. OFDI is a novel tool to observe the
      difference in the in-stent tissue characteristics. <Learning objective: In-stent
      restenosis (ISR) remains a clinical problem even in the drug-eluting stent (DES)
      era. The morphological assessment of ISR tissue using optical frequency-domain
      imaging (i.e. homogeneous, heterogeneous, and layered types) might be important
      to treat ISR lesions by percutaneous coronary intervention since the reaction to
      DES and drug-coating balloon seems to be different according to the in-stent
      tissue characteristics.>.

PMID- 30279865
TI  - Ablate and his bundle pace.
AB  - Atrioventricular junction (AVJ) ablation and pacing therapy is a safe and
      effective method to control heart rate in patients with atrial fibrillation and
      rapid ventricular rates who have failed pharmacologic rate control therapies.
      Usually, the pacing lead of the pacemaker is located at the right ventricular
      apex or septum, and sometimes the patient has a cardiac resynchronization therapy
      device with an additional lead implanted through the coronary sinus for left
      ventricular pacing. We present a 72-year-old woman with permanent atrial
      fibrillation who developed tachycardia-induced cardiomyopathy. She underwent AVJ
      ablation following pacemaker implantation with a single lead located at the His
      bundle region resulting in significant clinical and hemodynamic improvement at
      follow-up. <Learning objective: We present a case report of a 72-year-old woman
      with permanent atrial fibrillation who developed tachycardia-induced
      cardiomyopathy. She underwent atrioventricular junction ablation following
      pacemaker implantation with a single lead located at the His bundle region, as an
      alternative to the standard right ventricular apical pacing, with significant
      clinical and hemodynamic improvement at follow-up.>.

PMID- 30279866
TI  - A rare case of spontaneously dissolved calcification of the mitral annulus:
      Caseous calcification of the mitral annulus.
AB  - Caseous calcification of the mitral annulus is a rare variant of mitral annular
      calcification (MAC). MAC is detected using conventional echocardiography and is
      prevalent in the elderly. However, limited information is currently available on
      the transformation of MAC. We herein report a case of a sudden liquified change
      in MAC, which was diagnosed using echocardiography and computed tomography.
      <Learning objective: The mechanisms underlying the pathogenesis of caseous
      calcification of the mitral annulus (CCMA) have not been elucidated in detail.
      This case report revealed the transition from mitral annular calcification to
      CCMA, indicating the marked transformation of calcification, which leads to
      spontaneous liquefaction.>.

PMID- 30279867
TI  - Primary cardiac MYC/BCL6 double hit non-Hodgkin lymphoma.
AB  - Cardiac and pericardial involvement by malignant lymphoma is a rare condition.
      The present case report describes a case of primary cardiac MYC/BCL6 double hit
      non-Hodgkin lymphoma in the pericardium, and highlights the importance of a
      prompt diagnosis and aggressive pharmacologic treatment of this disease. In a
      symptomatic patient, a minimally invasive 3 cm sub-xiphoidal incision was
      performed under deep sedation with spontaneous ventilation to perform a
      pericardial biopsy. A 5 cm * 3 cm portion of pericardium was removed from above
      the right ventricle, thus ameliorating the extrinsic compression on the right
      chambers. The patient received 6 cycles of immuno-chemotherapy (rituximab plus
      cyclophosphamide, vincristine, and methylprednisolone), with no complications,
      achieving complete remission with no symptoms. Malignancies must be excluded in
      every case of acute pericardial disease with imaging techniques, and lymphomas
      should be always considered in the differential diagnosis of cardiac tumors.
      Complete surgical removal of the tumor is not necessary to achieve complete
      remission, and minimally invasive surgical approaches are an effective tool to
      confirm diagnosis and allow a precise histologic characterization. <Learning
      objective: Primary MYC/BCL6 double hit non-Hodgkin lymphoma is a rare tumor of
      the pericardium, which requires prompt diagnosis and treatment. Minimally
      invasive surgical approaches are an effective tool to confirm diagnosis and allow
      a precise histologic characterization. Pericardial tumors should always be
      considered in the differential diagnosis of acute pericardial disease presenting
      with pericardial effusion. Double hit diffuse large B cell-lymphoma has a poor
      prognosis with standard chemotherapy and the treatment should be tailored
      according to the patient's comorbidities and performance status.>.

PMID- 30279869
TI  - Endovascular entry closure using Amplatzer vascular plug for the aortic
      dissection in sub-acute phase.
AB  - Enlargement due to residual dissection after surgical ascending aortic
      replacement is technically challenging to treat. Endovascular entry closure using
      an Amplatzer vascular plug 2 (AVP2) in the sub-acute phase has not been reported.
      A 75-year-old female underwent emergent ascending aorta replacement for Stanford
      type A aortic dissection. Postoperative computed tomography angiography (CTA)
      showed a distal aortic arch diameter of 41 mm and a patent false lumen. CTA one
      month after the operation revealed distal aortic arch enlargement to 52 mm, which
      is considered high-risk for rupture. Repeat open surgery was considered but
      carried a high risk of perioperative complications. Therefore, we performed
      endovascular closure for the entry at the proximal descending aorta using an AVP2
      and stent graft coverage and coil embolization for the re-entries at the
      bilateral iliac arteries. CTA one month after the procedure revealed that the
      false lumen of the aortic arch was thrombosed and that the distal aortic arch had
      shrunk to 38 mm, indicating the efficacy of endovascular entry closure with the
      AVP2 after aortic dissection. <Learning objective: Endovascular entry closure for
      residual dissection more than 2 years after ascending aorta replacement has
      already been reported. We conducted this procedure in the sub-acute phase and
      induced favorable aortic remodeling. The endovascular entry closure was
      successfully conducted for a patient presenting residual tears after emergent
      ascending aorta replacement, considering a treatment option with high risk for
      repeat open surgery.>.

PMID- 30279868
TI  - A case of acute coronary syndrome caused by delayed coronary ischemia after
      transcatheter aortic valve implantation.
AB  - An 84-year-old female patient suffered from dyspnea due to severe aortic
      stenosis. Several comorbidities and her advanced age made her acceptable for
      transcatheter aortic valve implantation (TAVI). The TAVI procedure was performed
      via a femoral access and a 26-mm CoreValve prosthesis (Medtronic, Minneapolis,
      MN, USA) was implanted. The prosthesis was deployed at a high position because of
      short distance between the annulus base and coronary arteries. Aortic angiography
      indicated normal contrast flow into both coronary arteries. Six months later she
      was readmitted to our hospital because of acute coronary syndrome. Although
      selective intubation of coronary arteries could not be achieved because of high
      valve position, both coronary arteries seemed to be well contrasted. As a
      consequence, the second coronary angiography was undertaken because of recurring
      chest pains. The aortic root angiogram showed a decreased contrast flow into both
      coronary arteries. During the examination she deteriorated rapidly, developed
      cardiopulmonary arrest, and a percutaneous cardiopulmonary support and an intra
      aortic balloon pump needed to be inserted. She was then transferred to the
      operating room for aortic valve replacement. This is the first case of delayed
      coronary ischemia after TAVI, necessitating the removal of an implanted CoreValve
      and its replacement with a new prosthetic valve. <Learning objective: The higher
      position of the CoreValve implanted in the transcatheter aortic valve
      implantation (TAVI) procedure can rarely induce coronary obstruction, especially
      in patients with low lying coronary ostia and a small sinus of Valsalva.
      Percutaneous coronary intervention and coronary artery bypass graft are sometimes
      difficult in these patients, and replacement of the prosthetic valve may be an
      alternative. Patients with higher CoreValve position require close follow up to
      recognize any coronary perfusion defects at an early stage.>.

PMID- 30279870
TI  - Rapid snare sliding technique: An easy approach to difficult percutaneous
      transmitral commissurotomy.
AB  - Rheumatic heart disease (RHD) is a major health hazard in most developing
      countries as well as sporadically in developed economies with high prevalence
      rates. Mitral stenosis is among the important morbid valvular conditions
      accounting for 25% of RHD cases. Percutaneous transmitral commissurotomy (PTMC)
      using Inoue balloon is the standard treatment for severe mitral stenosis with
      favorable Wilkins score. In certain cases it is difficult to cross mitral valve
      (MV) either due to dilated left atrium (LA), low septal puncture, or severe
      mitral valvular and subvalvular stenosis leading to prolonged procedure time or
      failure of PTMC procedure. We describe a case of RHD with severe mitral stenosis
      and dilated LA where crossing MV was difficult and successful PTMC was performed
      using rapid snare sliding technique to cross the MV. <Learning objective:
      Percutaneous transmitral commissurotomy using Inoue balloon is the standard
      intervention used to treat severe mitral valvular stenosis worldwide. Sometimes
      we come across difficulty in crossing mitral valve (MV) due to varied reasons
      leading to failure of this technique. We present a case of rheumatic heart
      disease with severe mitral stenosis where we had difficulty to cross MV using
      various techniques and a rapid snare sliding technique was found to be quick,
      safe, and a good alternative with good results and few complications. We describe
      the interventional steps of this technique in this case report.>.

PMID- 30279871
TI  - Acute right ventricular failure and pulseless electrical activity arrest
      following auto-transfusion of blood.
AB  - Air embolism is a rare but potentially catastrophic complication of
      interventional procedures. The occurrence of acute right ventricular dysfunction
      during intraoperative auto-transfusion of blood, presumably related to pulmonary
      embolism of agitated air microbubbles and microthrombi, is less commonly
      recognized. We report a case of auto-transfusion complicated by acute right
      ventricular failure and pulseless electrical activity arrest. Auto-transfusion of
      recovered blood is a practical solution to reduce need for post-procedure
      allogenic transfusions. Although such interventions are frequently performed
      without complications, they do have inherent risks that should be readily
      acknowledged. This case clearly describes a severe complication and sequelae of
      auto-transfusion. <Learning objective: Auto-transfusion of recovered blood is
      commonly performed in surgical and interventional procedures to reduce the need
      for allogenic transfusion. Despite this benefit, the risks and complications of
      auto-transfusion can be severe and must be considered. We report a case of
      intraprocedural auto-transfusion resulting in introduction of air emboli and
      subsequent cardiac arrest. Additionally, we provide a brief review of air emboli
      and underlying pathophysiology that leads to cardiovascular decline.>.

PMID- 30279872
TI  - Simultaneous transcatheter aortic valve implantation and endovascular aneurysm
      repair in a patient with very severe aortic stenosis with abdominal aortic
      aneurysm.
AB  - The safety of non-cardiac surgery is uncertain for asymptomatic patients with
      very severe aortic stenosis (AS). Herein, we describe a case involving an elderly
      and frail patient with asymptomatic, very severe AS. The patient was considered a
      high-risk candidate for aortic valve replacement (AVR); thus, transcatheter
      aortic valve implantation (TAVI) was planned. On perioperative examination, an
      abdominal aortic aneurysm (AAA) was observed, which required endovascular
      aneurysm repair (EVAR). To reduce the risks involved with sequential procedures,
      TAVI and EVAR were performed simultaneously. In patients with severe AS who are
      high-risk candidates for AVR, TAVI can be considered as an alternative therapy
      before non-cardiac surgery. In addition, the combined TAVI and EVAR procedure can
      reduce the risks associated with the perioperative period. <Learning objective:
      For patients with severe aortic stenosis who are high-risk candidates for aortic
      valve replacement (e.g. elderly patients with comorbidities), transcatheter
      aortic valve implantation (TAVI) can be considered as an alternative therapy
      before non-cardiac surgery. In addition, combining TAVI and endovascular aneurysm
      repair can reduce the perioperative risks compared with those for sequential
      procedures. However, additional research is needed.>.

PMID- 30279873
TI  - Different behaviors of bioresorbable vascular scaffold in different types of
      calcified lesion: Insights from intravascular imaging.
AB  - A 55-year-old male underwent percutaneous coronary intervention (PCI) for left
      anterior descending artery chronic total occlusion. After lesion preparation with
      non-compliant (NC) balloon, two bioresorbable vascular scaffolds (2.5/28 mm,
      3.0/28 mm, Absorb BVS, Abbott Vascular, Santa Clara, CA, USA) were implanted
      followed by 1:1 sized NC balloon post-dilatation at 20 atm. Final intravascular
      ultrasound (IVUS) showed acceptable BVS expansion in diffusely calcified lesions.
      Twenty-one months' follow-up coronary angiography revealed severe restenosis with
      reocclusion at the distal edge of the distal BVS. After recanalization with a 1.0
      mm balloon, optical coherence tomography (OCT) was performed. Quantitative
      analysis comparing OCT and IVUS at the index procedure demonstrated that minimum
      scaffold area at follow-up became significantly smaller and with higher
      eccentricity, suggesting severe recoil at the lesions with thick calcium spot,
      whereas these changes were not observed at the lesion with relatively thin
      calcification. The lesions were successfully revascularized with drug-eluting
      stents and final OCT showed symmetric expansion of metallic stents. Our case
      demonstrates that different types of calcification can have an impact on BVS
      expansion and recoil. In calcified lesions, an optimal implantation technique is
      mandatory to achieve the best possible results, and characterization of calcified
      lesions with intravascular imaging may be helpful to decide PCI strategy with
      BVS. <Learning objective: Calcified lesions represent a challenging lesion subset
      for bioresorbable vascular scaffold (BVS) because of less radial strength of the
      latter. Quantitative analysis with intravascular imaging demonstrated that
      different types of calcification can have an impact on BVS expansion and recoil.
      In calcified lesions, an optimal implantation technique is mandatory to achieve
      the best possible results, and characterization of calcified lesions with
      intravascular imaging may be helpful to decide percutaneous coronary intervention
      strategy with BVS.>.

PMID- 30279874
TI  - Giant abdominal sarcoma that caused aortic rupture at the twelfth thoracic level.
AB  - There are no previous reports of intraabdominal sarcoma with metastasis to the
      thoraco-abdominal aorta causing rupture. Here we present the case of a previously
      healthy 50-year old male who presented to our institution with sudden, sharp back
      pain. Chest and abdominal computed tomography revealed aortic rupture at the
      twelfth thoracic level as well as a giant mass in the left upper abdomen. We
      performed thoracic endovascular aortic aneurysm repair. Histopathology of a
      biopsy taken from a rib metastasis was thought to be either differentiated
      liposarcoma or malignant fibrous histocytoma. The patient is currently undergoing
      chemotherapy. <Learning objective: Abdominal aortic rupture due to direct
      infiltration of sarcoma has been reported. However, there is no report that the
      metastasis of sarcoma caused the aortic rupture. Our report indicates the
      possibility that giant intraperitoneal sarcoma can cause aortic rupture due to
      para-aortic lymph node metastasis.>.

PMID- 30279875
TI  - Multiple coronary artery spasms triggering life-threatening ventricular
      arrhythmia associated with the radiofrequency ablation of ganglionated plexuses
      of the left atrium.
AB  - We report a case of multiple coronary spasms leading to life-threatening
      ventricular arrhythmia, during left atrium (LA) ablation. Coronary artery spasm
      is a rare complication during radiofrequency catheter ablation of atrial
      fibrillation (AF). Previous reports mention that autonomic imbalance leads to
      coronary artery spasm and ST-segment elevation in the inferior leads, during
      trans-septal LA catheterization and AF ablation procedures. However, there are
      few reports detailing the association between ablation sites and changes in the
      electrocardiogram. We encountered transient ST-segment elevation and refractory
      ventricular arrhythmia, associated with coronary artery spasm, during
      radiofrequency ablation of ganglionated plexuses (superior surface of left and
      right atrium). <Learning objective: Our case report shows that ablation of
      ganglionated plexus sites during pulmonary vein isolation, can induce ST-segment
      elevation in various leads, and cause multiple coronary spasms associated with
      refractory ventricular fibrillation. There is an inherent risk of multiple
      coronary spasms during catheter ablation of atrial fibrillation (AF), in patients
      with vasospastic angina. We recommend continuous intravenous infusion of
      nitroglycerin during ablation for AF to prevent coronary spasms in patients with
      vasospastic angina.>.

PMID- 30279876
TI  - A case of acute and late coronary events after blunt chest trauma: Attention to
      the late onset angina.
AB  - Mechanisms of acute myocardial infarction caused by traumatic coronary artery
      injury have been reported. However, late-onset coronary artery stenosis
      associated with trauma is less well known. We experienced a case in which acute
      myocardial infarction of the right coronary artery occurred at the time of blunt
      chest trauma (BCT) caused by a traffic accident and an increase in coronary
      artery stenosis in the left anterior descending artery (LAD) branch about 1 year
      later. A comparison of a volume-rendering image created from enhanced-contrast
      computed tomography at the time of trauma and coronary angiography revealed that
      the trauma site and the stenotic lesion in the LAD were in very close proximity,
      suggesting to us that traumatic coronary artery injury without flow limitation
      may have developed into high-grade stenosis in the LAD 1 year later. In this case
      we were able to demonstrate a causal relationship between BCT and delayed
      coronary artery stenosis. After BCT, it is necessary to be aware of the
      possibility of delayed coronary artery stenosis even if coronary injury is absent
      in the acute phase. <Learning objective: Careful follow up for the onset of
      angina pectoris is necessary to prevent coronary events after blunt chest
      trauma.>.

PMID- 30279877
TI  - Ultrasonographic and radiological imaging demonstrating an anomalous origin of
      the left coronary artery causing acute coronary syndrome in an adolescent.
AB  - We report the case of a 13-year-old girl who presented with cardiac collapse
      secondary to compression of the left main coronary artery (LMCA) between the
      pulmonary artery and the ascending aorta. In the acute phase, we performed
      aortography, intra-vascular ultrasound (IVUS), coronary computed tomography
      angiography (CCTA), transthoracic echocardiography (TTE), and transesophageal
      echocardiography (TEE). Aortography and CCTA showed that her LMCA was located
      between her pulmonary artery and the ascending aorta. IVUS and TEE showed that
      her LMCA was narrowed owing to compression by both great vessels during systole
      with release of the pressure during diastole. TTE and TEE showed that the left
      coronary artery flow was faster in the systole than that observed in the
      diastole. She was initially treated at our hospital but was transferred to
      another hospital for an unroofing operation. This was a rare case of a patient
      presenting with a coronary artery anomaly causing cardiac collapse. We conclude
      that her LMCA stenosis secondary to compression and narrowing of the great
      vessels led to her cardiac collapse. <Learning objective: A 13-year-old girl
      presented with cardiac collapse secondary to an anomaly of the left main coronary
      artery. Although, this anomaly is rare, it requires close and careful attention
      in the clinical setting. We reckon that the distinctive multi-modal images of
      this coronary artery anomaly that we present with this report are impressive and
      would be valuable to other clinicians.>.

PMID- 30279878
TI  - Concurrent diagnosis of infective endocarditis and acute rheumatic fever: A case
      report.
AB  - Rheumatic heart disease has been classically considered as a risk factor for
      infective endocarditis (IE). Although valvulitis is frequently present in
      patients with acute rheumatic fever (ARF), the established valve disease after
      initial episode of ARF is usually considered as a predisposing factor for IE. We
      hereby present a biopsy-proven case of IE co-diagnosed with the first episode of
      ARF. <Learning objective: Infective endocarditis and acute rheumatic fever are
      both diagnosed with clinical criteria. When both of these conditions are possible
      in a single case, however, the diagnosis might be challenging. We highlight this
      issue in the presented case.>.

PMID- 30279879
TI  - Successful alcohol septal ablation in a pregnant patient with symptomatic
      hypertrophic obstructive cardiomyopathy.
AB  - Hypertrophic cardiomyopathy is a clinically heterogeneous disease with common
      findings of ventricular hypertrophy, left ventricular outflow tract (LVOT)
      obstruction, mitral regurgitation, and diastolic dysfunction. Sometimes, the
      condition can lead to catastrophic cardiac events. Pregnancy can pose a larger
      challenge, due to medication restrictions associated with pregnancy. We report a
      case of a 43-year-old pregnant woman presenting with symptomatic hypertrophic
      obstructive cardiomyopathy (HOCM). As her pregnancy progressed, her HOCM worsened
      both symptomatically and by objective echocardiographic data. These changes
      continued despite optimized medical therapy. After an in-depth discussion with
      both the patient and family, we proceeded with alcohol septal ablation, which was
      successful in both reducing her LVOT gradient and her symptoms. Her pregnancy was
      overall uneventful, and both she and her child are doing well more than 4 years
      from the date of the procedure. <Learning objective: While medical therapy is the
      first-line approach to patients with hypertrophic cardiomyopathy (HCM), symptoms
      may still persist despite optimized medical therapy. If medical therapy fails in
      a pregnant patient with symptomatic HCM and a significant left ventricular
      outflow tract gradient, successful alcohol septal ablation can improve the
      gradient and relieve symptoms.>.

PMID- 30279880
TI  - Acute peri-operative coronary subclavian steal syndrome: A diagnostic and
      treatment challenge.
AB  - The coronary subclavian steal syndrome (CSSS) generally occurs during follow up
      after coronary surgery. The case demonstrates an immediate peri-operative CSSS
      followed by myocardial infarction, notwithstanding a preoperative computed
      tomography scan quantifying subclavian artery calcifications as non-stenosing,
      and a subjective patent blood flow through the transected left internal mammary
      artery (LIMA). Blood flow inversion in the LIMA to anterior descending artery
      (LAD) bypass was detected by transit time flow measurement (TTFM). Following an
      elective brachiocephalic bypass a complementary, emergent subclavian bypass was
      performed, which restored antegrade LIMA flow, as confirmed by TTFM and
      angiography, but the patient suffered a peri-operative myocardial infarction.
      Reports about elective, concomitant subclavian and coronary surgery for sub-acute
      CSSS, allowing diagnostic investigations, have been published; however this case
      demonstrates diagnostic and treatment challenges in acute CSSS and emphasizes the
      role of peri-operative TTFM. <Learning objective: Despite a visible, pulsatile,
      and apparently patent antegrade flow through the left internal mammary artery,
      blood flow inversion through the completed bypass, creating acute myocardial
      ischemia, is possible. The recognition of this, potentially severe, ischemic
      complication during bypass surgery might not be evident without transit time flow
      measurement, due to poor clinical signs. The major learning objective is the fast
      recognition of this complication, preventing infarction and reducing operative
      morbidity and mortality in the future in similar settings.>.

PMID- 30279881
TI  - The histological findings in transposition of the great artery with severe
      persistent pulmonary hypertension of the newborn.
AB  - The combination of persistent pulmonary hypertension of the newborn (PPHN) and
      transposition of the great arteries (TGA) has serious impacts on treatment and
      prognosis, often with adverse outcomes. We report the case of a male full-term
      newborn with TGA with intact ventricular septum and severe PPHN who died 2 h
      after birth; further, we examined his vascular histology. On autopsy, lung
      histology showed mild fibrous hypertrophy in the intima and moderate medial
      hypertrophy of the minimal pulmonary artery. Hypoplasia of the pulmonary artery
      was not detected. Pulmonary congestion was detected and pneumatization was poor.
      Debris was present in the alveoli. Hemosiderin deposition was detected,
      suggesting prenatal hemostasis or hemorrhage. Severe PPHN may have occurred
      because of pulmonary arterial spasm accompanying pulmonary congestion which had
      been in the fetal stage. A wide range of lesions can be present in the pulmonary
      vascular bed in TGA. The pathologies of pulmonary vascular tissues with TGA and
      PPHN are not uniform. <Learning objective: Neonates with transposition of the
      great arteries with intact ventricular septum (TGA/IVS) may have severe pulmonary
      hypertension. The progression of pulmonary vascular disease in TGA/IVS is
      unpredictable; therefore, the delivery of a fetus diagnosed with TGA/IVS should
      be performed at an institution in which catheterization and balloon atrial
      septostomy can be performed.>.

PMID- 30279882
TI  - Transcatheter aortic valve implantation in a patient with severe aortic valve
      stenosis, colon cancer, and obstructive ileus: A case report.
AB  - An 82-year-old woman with symptomatic severe aortic stenosis (AS) developed an
      obstructive ileus caused by colon cancer. Colectomy was considered a high-risk
      surgery due to both the severe AS and obstructive ileus. Therefore, we planned
      placement of a colonic stent for the obstructive ileus. After stenting, we
      performed transcatheter aortic valve implantation (TAVI) instead of surgical
      aortic valve replacement (SAVR), because of the risk of bleeding during
      extracorporeal circulation and the perioperative risk of AVR (Society of Thoracic
      Surgery predicted risk of mortality: 7.4%). Successful colonic stenting and TAVI
      allowed a safer colectomy. The period from TAVI to colectomy was 12 days. TAVI
      could be useful for symptomatic severe AS in high-risk patients prior to non
      cardiac surgery, especially for malignant tumors. <Learning objective: In
      patients with symptomatic severe aortic stenosis, aortic valve replacement is
      recommended prior to non-cardiac surgery. However, in patients with a malignancy,
      the complications due to the tumor and the risk of extracorporeal circulation
      remain a challenge in surgical aortic valve replacement. In such cases,
      transcatheter aortic valve implantation may be a useful option to reduce the
      incidence of complications and the time to surgery for the malignancy.>.

PMID- 30279883
TI  - A case of conservative management for left ventricular giant pseudoaneurysm
      without ST segment changes.
AB  - Left ventricular (LV) rupture after myocardial infarction (MI) occasionally
      results in formation of LV pseudoaneurysm (LVPA) which is prone to rupture
      because of its thin wall. However, cases of LVPA without ST changes including
      segment elevation in electrocardiogram (ECG) are rare. In this case, we describe
      a patient who had relatively mild symptoms and giant LVPA with no specific ECG
      changes following MI with a confirmed diagnosis via transthoracic
      echocardiography. Although surgical treatment options are often recommended,
      conservative therapy was adopted, following which the patient had been well
      medicated using antihypertensive drugs and anticoagulants. <Leaning objectives:
      Left ventricular pseudoaneurysm (LVPA) is usually accompanied by ST segment
      changes on electrocardiogram (ECG) due to myocardial damage. However, we should
      take into account a LVPA without ECG specific changes, so echocardiography is
      better to be considered for an identification. Although many LVPA patients
      undergo surgery because of risk for rupture, some cases with stable hemodynamic
      status can have long-term survival with conservative therapy such as anti
      hypertension and coagulation.>.

PMID- 30279884
TI  - Reversible atrioventricular block and the importance of close follow-up: Two
      cases of Lyme carditis.
AB  - Lyme carditis is an uncommon presentation of the early-disseminated phase of Lyme
      disease, although it is recognizable and often curable. Because of its rarity,
      diagnosing Lyme carditis requires a high level of suspicion, especially when
      young patients in certain endemic areas present with symptoms of bradycardia
      and/or evidence of high-degree atrioventricular (AV) block. Temporary cardiac
      pacing along with antibiotic therapy has been shown to aid in the management of
      Lyme carditis until symptoms and conduction blocks have resolved. Herein, we
      report two cases of Lyme carditis-induced AV block that were successfully managed
      and reversed with temporary cardiac pacing and antibiotics. In order to monitor
      for any late sequela that may arise, we also recommend close follow-up for
      patients treated for Lyme carditis with high-degree AV block. <Learning
      objective: Lyme carditis manifests as a conduction system disease, predominantly
      involving the atrioventricular (AV) node. It can present without the classical
      signs of Lyme disease. It is critical to have a high suspicion of Lyme carditis
      in patients who present with symptoms of bradycardia or high-degree AV block in
      high prevalence areas. Early initiation of antibiotics, along with external
      temporary pacing, dramatically improves mortality rates. Close follow-up is
      important in patients that develop high-degree AV block.>.

PMID- 30279885
TI  - Recurrent nonbacterial thrombotic endocarditis: A novel therapeutic approach.
AB  - We present the case of a 29-year-old male with a history of Mizuho hemolytic
      anemia, a rare form of unstable hemoglobinopathy, who presented with congestive
      heart failure secondary to recurrent valve thrombosis despite appropriate oral
      anticoagulation. He subsequently required mitral and aortic valve replacement.
      Pathologic examination revealed extensive nonbacterial thrombotic endocarditis.
      Due to recurrent thrombosis despite therapeutic anticoagulation, we elected to
      treat him with red blood cell exchange transfusions and hydroxyurea. He has
      remained free of symptoms for almost two years with this treatment regimen
      without side effects. <Learning objective: The management of nonbacterial
      thrombotic endocarditis (NBTE) is well described in the literature. However, the
      treatment for refractory NBTE in aggressive forms of unstable hemoglobinopathy
      remains difficult. The use of hydroxyurea and serial red blood cell exchange, in
      addition to the usual therapies, may be useful in the treatment of refractory
      NBTE.>.

PMID- 30279886
TI  - Limited effects of long-term enzyme replacement therapy on the cardiac conduction
      system in Fabry disease.
AB  - The long-term effects of enzyme replacement therapy (ERT) on cardiac function and
      the conduction system in Fabry disease are not clearly understood. We report a
      case of a 48-year-old man with non-classical Fabry disease treated with ERT for
      11 years. He was diagnosed with Fabry disease at age 27 years based on the
      presence of decreased alpha-galactosidase A activity in the peripheral leukocytes
      and of the causal alpha-galactosidase A mutation (Val339Gln). Subsequently,
      peritoneal dialysis was initiated for renal failure at age 35 years. ERT was
      initiated at age 39 years to halt the progression of cardiac dysfunction.
      Electrical conduction disturbances progressed gradually to complete
      atrioventricular block with atrial standstill during 9 years of ERT despite the
      lack of progression of ventricular hypertrophy. Although he underwent permanent
      pacemaker implantation to prevent sudden cardiac death, the atrioventricular
      junctional rhythm remained, thereby lowering the ventricular pacing rate. Based
      on this case, we recognize that the effects of ERT are limited for inhibiting the
      progression of Fabry disease and especially for inhibiting arrhythmia and
      conduction disturbances. Early diagnosis of Fabry disease and early initiation of
      ERT might be the key to further improvements in this disease and its associated
      conditions. <Learning objective: We encountered a patient with Fabry disease
      treated with long-term enzyme replacement therapy (ERT) in whom conduction
      disturbances progressed without progression of left ventricular hypertrophy. This
      case suggests that ERT is limited for inhibiting the progression of Fabry disease
      and especially of arrhythmia and conduction disturbances. Early diagnosis of
      Fabry disease and initiation of ERT may be important for providing further
      improvements of this condition.>.

PMID- 30279887
TI  - A single-stage hybrid approach for the management of severely stenotic bicuspid
      aortic valve, ascending aortic aneurysm, and coarctation of the aorta with a
      literature review.
AB  - The combination of aortic stenosis in the context of bicuspid aortic valve,
      aneurysmal dilatation of the ascending aorta, and coarctation is not uncommon.
      This condition has conventionally been addressed either by a complex open
      surgical approach or by staged hybrid approach combining open surgery of the
      ascending aorta with subsequent endovascular stenting of the coarctation. So far,
      the risk of a complex open approach for the aortic valve and ascending aorta and
      the cumulative risk of a staged second procedure for management of the
      coarctation are unknown; and similarly, the risk of a complex single-staged
      surgical procedure as an option instead of a single-staged hybrid approach is
      unknown. For the first time, we present a case of a patient with bicuspid
      aortopathy and concomitant coarctation who was simultaneously managed with both
      stenting of the coarctation and subsequent surgical replacement of the aortic
      valve and ascending aorta in one session. This new strategy has potential to
      become a future standard of care with various advantages. <Learning objective:
      Endovascular techniques are more frequently being used in the management of
      coarctation of the aorta, especially when associated with other cardiac
      pathologies. The definitive role of these techniques is still to be defined. A
      review of the risks and benefits of different management strategies may be
      beneficial with regard to making the right choice for each patient and a hybrid
      technique may be superior to purely surgical management, especially in a high
      risk patient.>.

PMID- 30279888
TI  - Effect of subcutaneous oxycodone for end-stage heart failure due to severe aortic
      stenosis - A case report.
AB  - It is difficult to manage the symptoms of patients who are dying of end-stage
      heart failure (HF). Opioids are sometimes required to relieve their symptoms in
      addition to oxygen therapy and medical management. Oxycodone is a MU receptor
      agonist that is known to be a safer opioid than morphine in patients with chronic
      kidney disease (CKD) because its metabolites have weak pharmacological activity.
      We treated a 99-year-old woman who had end-stage HF (secondary to severe aortic
      stenosis) and CKD. It was also difficult to maintain an intravenous line because
      of severe edema. We administered oxycodone subcutaneously and successfully
      alleviated her severe symptoms without severe adverse effects of opioids until a
      few days before her death. We report this case and discuss the possibility of
      using subcutaneous oxycodone as a new palliative care strategy in patients with
      end-stage HF. <Learning objective: We report the management of chest symptoms of
      an elderly patient with end-stage heart failure (HF) due to severe aortic
      stenosis by subcutaneous infusion of oxycodone. This method has a possibility to
      alleviate chest symptoms of end-stage HF with less severe adverse effects until a
      few days before death than morphine, and may be useful to manage the symptoms
      even in patients with severe edema. Further investigation will be required to
      compare subcutaneous oxycodone with intravenous morphine.>.

PMID- 30279889
TI  - Right coronary artery fistula with giant pseudoaneurysm presenting as
      intrapericardial mass.
AB  - Coronary artery fistulas are rare congenital anomalies usually discovered
      incidentally on imaging studies. Coronary artery pseudoaneurysms are unusual
      complications of coronary artery fistulas, which can be due to atherosclerosis,
      inflammatory, traumatic or iatrogenic causes. We present a case of a 55 year old
      female with no known atherosclerotic risk factors, history of trauma or
      connective tissue disease referred because of recurrent palpitations. Work ups
      revealed a cardiac mass with an initial assessment of pericardial cyst. A multi
      modality approach of two dimensional echocardiography with Doppler studies,
      multidetector computed tomography and coronary angiogram revealed coronary artery
      fistula draining into a pericardial mass. The patient underwent surgical excision
      of the mass and ligation of the feeding vessel. Histopathology revealed features
      suggestive of a pseudoaneurysm. Postoperative course was uneventful and she was
      discharged stable and improved. Coronary artery fistula complicated by
      pseudoaneurysm is a rare clinical entity especially in patients without history
      of trauma or other risk factors. It can have an unusual presentation which can
      confound the diagnosis. Multimodality imaging is essential and adjunctive in
      order to determine a conclusive assessment. <Learning objective: Coronary artery
      pseudoaneurysm secondary to a congenital coronary artery fistula is an unusual
      cardiovascular pathology and can present as a rare diagnostic challenge for the
      clinician. This case emphasizes the importance of meticulous integration of both
      clinical assessment and complementary multimodality imaging approaches to better
      define the best therapeutic plan and facilitation of definitive surgical
      management.>.

PMID- 30279890
TI  - Left ventricular reverse remodeling after transcatheter aortic valve implantation
      complicated by paroxysmal complete atrioventricular block.
AB  - An 86-year-old man with unremarkable clinical history complaining of asthenia and
      dyspnea was diagnosed with low-flow low-gradient aortic stenosis [LFLG-AS; left
      ventricular ejection fraction (LVEF) 40% and transaortic mean gradient 37 mmHg,
      increasing to 52% and 55 mmHg after dobutamine infusion]. The patient underwent
      transcatheter aortic valve implantation (TAVI; Edwards CENTERATM 29, Irvine, CA,
      USA). The procedure and the following hospital stay were free from complications,
      with no changes on electrocardiography (ECG). Six months later, few syncopal
      episodes occurred. No signs of orthostatic hypotension or neurologic disorders
      were present. Echocardiography showed normal functioning of the prosthetic valve
      and recovery of LV systolic function (LVEF 55%). Baseline ECG and 24-h Holter
      monitoring were unremarkable. An implantable loop recorder (ILR) was implanted to
      verify the occurrence of paroxysmal conduction disturbances. One month later,
      during a syncopal episode, ILR interrogation showed a complete atrioventricular
      (AV) block. Therefore, a dual chamber, single lead pacemaker was implanted. We
      are providing the first report of complete AV block occurring months after TAVI,
      possibly because of reverse LV remodeling following TAVI, with ensuing relative
      oversizing of the prosthetic valve. This possibility should be considered in
      patients with syncope not otherwise explained, and previous TAVI, especially in
      cases of LFLG-AS. <Learning objective: Complete atrioventricular block can occur
      even months after transcatheter aortic valve implantation (TAVI), possibly
      because of left ventricular reverse remodeling following valve replacement, with
      ensuing relative valve oversizing. This possibility should be considered in
      patients with syncope not otherwise explained, and previous TAVI, especially in
      cases of low flow low gradient aortic stenosis. Loop recorder implantation should
      be considered in this group of patients.>.

PMID- 30279891
TI  - Familial pulmonary thromboembolism with a prothrombin mutation and antithrombin
      resistance.
AB  - We describe the case of a 45-year-old man with congenital thrombophilia induced
      by antithrombin resistance. He had recurrent venous thrombosis without
      traditional risk factors or abnormal coagulation function and had a family
      history of venous thrombosis which included his mother, brother, and nephew. We
      suspected the association of hereditary antithrombin resistance, which has been
      reported in some cases of familial venous thromboses due to prothrombin
      mutations. Although prothrombin abnormality typically shows a bleeding tendency,
      variations of arginine at position 596 in the gene encoding prothrombin have been
      reported to conversely cause thrombosis. Therefore, we tested and detected
      antithrombin resistance in the patient's plasma. We also performed genetic
      analysis for his second filial generation, and found a missense mutation
      (c.1787G>A), resulting in a substitution of arginine for glutamine at position
      596 (p.Arg596Gln) in the gene encoding prothrombin (called prothrombin Belgrade).
      The Gln596 substitution caused the susceptibility to thrombosis. This variation
      is the same as one previously reported in Serbia and India, and it is the third
      report in Japan. <Learning objective: Venous thrombosis is caused by multiple
      factors. However, approximately 20% of the patients with venous thrombosis of
      unknown cause have no risk factors. The present case had no known risk factors,
      rather he has a family history of thrombosis. Therefore, we suspected an
      association with inherited thrombophilia. Although several gene mutations have
      been found in some families with inherited thrombophilia, many mutations remain
      to be detected.>.

PMID- 30279892
TI  - Emergent caesarean section under mechanical circulatory support for acute severe
      peripartum cardiomyopathy.
AB  - Peripartum cardiomyopathy (PPCM) is an idiopathic left ventricular dysfunction in
      women who are in late pregnancy or the postpartum period. PPCM is a rare but
      sometimes fatal disease, and mechanical circulatory support is required if heart
      failure is refractory to conventional therapy. A 28-year-old woman in late
      pregnancy was admitted to our hospital due to congestive heart failure with
      cardiogenic shock. Her heart rate was 200 beats per minute (sinus tachycardia),
      and left ventricular ejection fraction (LVEF) was 10%. Additionally, fetal heart
      rate decreased to 80 beats per minute. It was extremely difficult to continue her
      pregnancy because of decompensated heart failure and fetal asphyxia; therefore,
      we delivered her baby via caesarean section after initiating mechanical
      circulatory support. With optimal medical therapy, including bromocriptine, we
      were able to remove mechanical circulatory support. Additionally, LVEF improved
      to 42%, and she was discharged with her baby who had no growth failure. This case
      highlights the safety and risk of caesarean section under mechanical circulatory
      support, and the effectiveness of bromocriptine. <Learning objective: Mechanical
      circulatory support is occasionally required if heart failure is refractory to
      conventional medical therapy in peripartum cardiomyopathy (PPCM). Mechanical
      circulatory support, particularly extracorporeal membrane oxygenation needing
      sufficient anticoagulation, should be initiated following delivery via caesarean
      section because of bleeding from the uterus. Moreover, bromocriptine may be
      effective in improving PPCM and should be the first-line treatment in clinical
      practice.>.

PMID- 30279893
TI  - Multiple potency of ezetimibe in a patient with macroproteinuric chronic kidney
      disease and statin-intolerant dyslipidemia.
AB  - Dyslipidemia is often complicated by chronic kidney disease (CKD). Lipid-lowering
      medications may be effective, in part, for inhibiting development and progression
      of CKD. Ezetimibe, a cholesterol absorption inhibitor, has pleiotropic actions,
      including anti-inflammatory and anti-oxidant effects, contributing to a decreased
      risk of cardiovascular diseases. A 40-year-old woman was admitted with
      dyslipidemia and macroproteinuria, whose samples of renal biopsy showed exudative
      lesions, but without glomerular basement membrane thickening or nodular lesions,
      in some glomeruli. Blood glycemic parameters were normal. After initiation of
      atorvastatin, she developed muscle pain and an increase in serum creatine kinase.
      Twelve months after switching to ezetimibe, serum levels of low-density
      lipoprotein cholesterol and triglyceride reduced from 170 mg/dL to 116 mg/dL and
      from 320 mg/dL to 160 mg/dL, respectively. Although serum creatinine levels
      remained unchanged after 12 months, urinary protein excretion and urinary liver
      type fatty acid binding protein were reduced. Flow-mediated dilatation also
      increased from 4.9% to 5.5% after 12 months, associated with a slight decrease in
      mean intima-media thickness in the common carotid artery from 0.722 mm to 0.718
      mm. These results suggest that ezetimibe protects against renal and vascular
      damage in patients with CKD and statin-intolerant dyslipidemia. <Learning
      objective: Little is known whether ezetimibe monotherapy is safe and effective
      for renal/vascular function in patients with chronic kidney disease (CKD). We
      report that ezetimibe monotherapy for 12 months improved lipid profiles in a
      patient with CKD and statin-intolerant dyslipidemia. Ezetimibe also reduced
      proteinuria and urinary liver-type fatty acid binding protein levels, improved
      endothelial function, and decreased carotid atherosclerosis. These findings
      suggest that ezetimibe monotherapy may have beneficial multipotent effects on
      renal/vascular function.>.

PMID- 30279894
TI  - Transcatheter aortic valve implantation for severe aortic stenosis in
      dextrocardia with situs inversus using a self-expanding aortic valve.
AB  - Transcatheter aortic valve implantation (TAVI) has evolved into a standard
      therapy for aged patients with severe aortic valve stenosis who are not
      candidates for surgery. However, the reports about the safety of TAVI for
      patients with dextrocardia situs inversus are few. An 84-year-old man with
      dextrocardia situs inversus underwent a TAVI for severe aortic stenosis (AS) with
      an aortic valve area of 0.5 cm2, and a mean pressure gradient of 46 mmHg.
      Preoperative computed tomography (CT) revealed an inverted (rightward)
      orientation of the ventricle apex as well as the great vessels. The TAVI was
      performed through a transfemoral approach under general anesthesia. A left and
      right reversed fluoroscopic image was used for the TAVI. Finally, a 26-mm
      CoreValve Evolut R (Medtronic, Minneapolis, MN, USA) was successfully deployed at
      the aortic annulus under angiographic guidance. Post-procedural transthoracic
      echocardiography demonstrated a well-functioning CoreValve Evolut R with a mean
      pressure gradient of 8 mmHg. No complications occurred during the procedure or
      peri-procedural period. The patient's symptoms subsequently improved from New
      York Heart Association class III to class I. In conclusion, a TAVI procedure was
      safely performed in a patient with dextrocardia situs inversus through a
      transfemoral approach by evaluating the anatomical details with preoperative CT.
      <Learning objective: Transcatheter aortic valve implantation (TAVI) has evolved
      into a standard therapy for aged patients with severe aortic valve stenosis who
      are not candidates for surgery. On the other hand, dextrocardia situs inversus is
      associated with a number of additional cardiac and vascular malformations. In
      this case, we report on a case in which a TAVI procedure was safely performed in
      a patient with dextrocardia situs inversus through a transfemoral approach.>.

PMID- 30279896
TI  - Pseudo-vanishing lung syndrome in a patient with tricuspid valve bacterial
      endocarditis.
AB  - Infective endocarditis is a major cause of morbidity and mortality among
      individuals with opioid use disorder who use injection drugs. It is frequently
      associated with tricuspid valve endocarditis and Staphylococcus aureus
      bacteremia, with secondary pulmonary septic emboli. Herein, we report a unique
      case of pulmonary cavitation injury following pulmonary septic emboli in the
      setting of tricuspid valve endocarditis in an injection drug user with opioid use
      disorder. The pattern of cavitary lung injury mimics radiographically
      indistinguishable features from vanishing lung syndrome during the most advanced
      stage of her illness. <Learning objective: This manuscript aims to highlight a
      new complication of bacterial endocarditis secondary to septic emboli showered
      from the infected tricuspid valve. This complication, which resembles a pulmonary
      disease by the name of vanishing lung syndrome, is characterized by extensive
      pneumatoceles that give the appearance of vanishing lung on chest radiography.>.

PMID- 30279895
TI  - Leadless pacing in a patient with superior vena cava syndrome undergoing lead
      extraction and percutaneous angioplasty.
AB  - Superior vena cava (SVC) syndrome is an uncommon but serious complication
      associated with chronic transvenous implanted leads. In the recent past, open
      heart surgery combining lead extraction and epicardial implant was usually
      performed to reduce syndrome recurrences. We describe the case of a 78-year-old
      man successfully treated by percutaneous lead extraction associated with venous
      balloon angioplasty and reimplantation of leadless pacemaker. <Learning
      objective: Chronic vascular complications following lead implantation usually
      require surgical treatment, due to the need for subsequent epicardial
      implantation. Percutaneous lead extraction along with leadless pacing allowed
      effective non-surgical management of chronic complications of transvenous
      pacing.>.

PMID- 30279897
TI  - Right internal jugular vein thrombosis caused by aneurysm of right-sided aortic
      arch.
AB  - A right-sided aortic arch is normally asymptomatic. We report the case of an 84
      year-old man with right internal jugular vein thrombosis caused by an aneurysm in
      a right-sided aortic arch. The patient had undergone open repair of an abdominal
      aortic aneurysm and had an uneventful postoperative course. However, a routine
      postoperative contrast-enhanced thoracic and abdominal computed tomography scan
      showed right internal jugular vein thrombosis. The patient had no history of
      catheter insertion in the right jugular veins and had no hereditary coagulopathy.
      It was presumed that the cause of this thrombosis was compression of the right
      brachiocephalic vein by an aneurysm of the right-sided ascending aorta that was
      considered too small to require surgical repair. The right internal jugular vein
      thrombosis was successfully treated with edoxaban. <Learning objective: This case
      report alerts us to consider that a right-sided aortic arch aneurysm considered
      too small for surgery can later cause upper-extremity deep vein thrombosis.>.

PMID- 30279898
TI  - Subacute aortic regurgitation due to traumatic tear in the aortic wall.
AB  - A 37-year-old man presented with heart failure caused by severe aortic
      regurgitation (AR). He had a history of being involved in a traffic accident 3
      months earlier. Imaging tests at admission detected no abnormalities in the
      aortic valve or aortic wall; however, the left coronary cusp prolapsed slightly
      on transthoracic echocardiography. He underwent aortic valve replacement because
      of uncontrolled heart failure and severe AR. Intraoperatively, the intima of the
      aortic wall just above the commissure of the left and right coronary cusps was
      torn to the short axial direction. Local aortic tear was the final diagnosis for
      the subacute AR. <Learning objective: Acute or subacute aortic regurgitation (AR)
      is comparatively rare, and it is sometimes difficult to clinically recognize. The
      tear in the aortic wall just above the commissure caused by a traffic accident
      led to the gradual progression of AR, and the diagnosis of the cause of AR was
      difficult despite using transesophageal echocardiography and contrast-enhanced
      computed tomography. We should recognize that the detection of subacute AR caused
      by a local aortic tear can be challenging.>.

PMID- 30279899
TI  - Hemorrhagic shock due to branch injury of the left internal thoracic artery two
      days after pericardiocentesis.
AB  - Pericardiocentesis is a definitive strategy to remove pericardial effusion. In
      this report, we present a rare case of a 23-year-old man with sudden delayed
      hemorrhagic shock due to branch bleeding of the left internal thoracic artery
      (LITA) two days after undergoing pericardiocentesis. Angiography, embolization,
      and drainage were effective. As far as we know, this is the first report that
      shows delayed bleeding due to branch injury of the LITA as a possible
      complication after pericardiocentesis. <Learning objective: Pericardiocentesis
      using an apical approach under echocardiography is considered safe; however, in
      this case, unexpected complications after pericardiocentesis for hemorrhagic
      shock occurred. Patients who undergo pericardiocentesis should be observed in the
      hospital for several days. If sudden changes in vital signs occur, the underlying
      complications should also be considered, and it is important to act promptly and
      review the patient's prior procedures.>.

PMID- 30279900
TI  - Pacemaker malfunction after acute myocardial infarction in a patient with wrap
      around left anterior descending artery supplying the right ventricular apex.
AB  - A 50-year-old man with a dual-chamber pacemaker was admitted to our hospital
      complaining of chest pain. Anterior ST segment elevation myocardial infarction
      (STEMI) was diagnosed. Emergency coronary angiography revealed total occlusion of
      the proximal left anterior descending artery (LAD), and primary percutaneous
      coronary intervention was performed. Angiograms showed that the LAD was wrapped
      around the apex of both ventricles. On day 8, ventricular fibrillation and
      cardiopulmonary arrest occurred due to elevation of the pacing threshold because
      of pacemaker malfunction. The pacemaker was upgraded to an implantable
      cardioverter-defibrillator and the lead was inserted into the right ventricular
      septum. Myocardial scintigraphy with thallium-201 and technetium-99m
      pyrophosphate located the infarct zone around the apex of both ventricles. We
      conclude that pacing failure of the right ventricular lead occurred in this case
      of LAD occlusion due to a LAD supplying the right ventricular apex. Clinicians
      should be aware of the possibility of pacemaker failure in patients presenting
      with anterior STEMI due to a wrap-around LAD. <Learning objective: Pacemaker
      failure due to right ventricular lead malfunction can also occur in patients
      presenting with myocardial infarction of the left coronary arteries. In our case
      the culprit lesion was located in the left anterior descending artery, which
      wrapped around the apex to supply parts of the right ventricle.>.

PMID- 30279902
TI  - Simultaneous suction debulking of lead vegetation prior to percutaneous lead
      extraction.
AB  - The infection rates of implanted cardiac devices have increased disproportionate
      to the dramatic increase in implantation rates, possibly related to rising
      patient comorbidities. Optimum strategy in cases with larger size vegetations,
      however, remains to be ascertained. In the absence of an effective and less
      invasive alternative, such patients usually undergo open thoracotomy for lead
      extraction. We describe the case of a 50-year-old female presenting with
      recurrent methicillin-resistant Staphylococcus aureus bacteremia found to have 3
      cm highly mobile vegetation on the right ventricular lead of her implanted
      defibrillator. While being intermediate-to-low surgical risk, she underwent
      AngioVac-directed suction debulking (AngioDynamics, Latham, NY, USA) of the
      vegetation simultaneously preceding percutaneous laser lead extraction in a
      single session. This less invasive alternative to open thoracotomy has been
      described in high surgical risk patients, but its widespread role remains
      unexplored. <Learning objective: Complete lead extraction is recommended in all
      cases of lead infection. However in the presence of large-size lead vegetation,
      the optimum management strategy is still controversial, especially among high
      risk surgical patients. AngioVac system (AngioDynamics, Latham, NY, USA) has a
      centrifugal suction cannula which can offer a safer and less invasive
      percutaneous alternative to open thoracotomy approach, with a possibility of
      large-scale application due to faster recovery.>.

PMID- 30279901
TI  - Two rare cases of congenital aortic stenosis showing a discrepancy between
      preoperative imaging diagnosis, intraoperative findings, and histopathological
      diagnosis.
AB  - Unicuspid aortic valve (UAV) is an extremely rare congenital heart valve
      abnormality while bicuspid valve (BAV) has been reported as one of the most
      common cardiac anomalies. With a UAV usually showing similar presentations to a
      BAV, such as aortic regurgitation or aortic stenosis (AS), it is challenging to
      differentiate them from each other in clinical settings. Despite some features
      shared between both valve disorders, there can be a clinical significance in
      distinguishing UAV from BAV for the management of patients with these heart
      anomalies. Herein, we describe two cases where patients with hemodynamically
      severe AS were diagnosed with BAV and UAV, respectively based on preoperative
      examinations and intraoperative findings, but subsequent pathological
      examinations confirmed the opposite diagnosis in both cases. <Learning objective:
      Preoperative diagnosis of congenital aortic valve diseases can often be
      challenging. There remains a remarkable number of misleading cases. Thus, it is
      strongly recommended that an accurate diagnosis should be attempted at the
      earliest stages of congenital aortic valve disease. Additionally, both careful
      follow-ups using multiple imaging modalities and confirmations via pathological
      diagnosis for patients undergoing surgery, if they are first found to be at an
      advanced stage or remain undiagnosed preoperatively are important.>.

PMID- 30279903
TI  - Left ventricle pseudoaneurysm: Diagnosis by a new murmur.
AB  - Incomplete rupture of the ventricle free wall can occur after myocardial
      infarction. This occurs when an organized thrombus and the pericardium seal the
      ventricular perforation. This can progress to the formation of a left ventricle
      pseudoaneurysm (LVPA). A 70-year-old male with an antero-septal ST-elevation
      myocardial infarction (STEMI) underwent an emergent left heart catheterization
      which revealed severe three-vessel disease with occluded grafts, non-amenable to
      re-vascularization, and an apical thrombus. As he was high-risk for repeat
      coronary artery bypass graft, he was medically managed. Transthoracic
      echocardiogram (TTE) showed a normal left ventricle ejection fraction (LVEF),
      apical anterior and inferior wall akinesis, moderate sized apical thrombus, and
      pericardial thickening. On hospital day 7, examination revealed a new 3/6 to-and
      fro murmur that was loudest at the apex. The patient was asymptomatic with normal
      vital signs. A repeat TTE revealed an apical wall rupture with flow into the
      pericardial cavity and absence of the apical thrombus. A LVPA was diagnosed and
      the patient was immediately referred for surgical repair. This case illustrates
      the potential for developing LVPA in STEMI patients and the importance of
      physical examination. If identified early a potential emergent situation in a
      previously asymptomatic patient can be averted, thereby preventing fatal
      consequences. <Learning objective: With the growing use of diagnostic testing the
      importance of physical examination is being lost. However, with an astute cardiac
      examination, potential complications such as a left ventricular pseudoaneurysm
      can be identified and promptly managed. In addition, a ventricular pseudoaneurysm
      must be considered in the differential as a rare complication in post ST
      elevation myocardial infarction patients with a new murmur.>.

PMID- 30279904
TI  - Atrial tachycardia originating from an incompletely isolated box lesion in a
      patient undergoing thoracoscopic left atrial appendectomy and surgical ablation
      for long-standing persistent atrial fibrillation.
AB  - The efficacy of pulmonary vein isolation for persistent atrial fibrillation or
      long-standing persistent atrial fibrillation is limited. Thoracoscopic surgical
      ablation was introduced as an alternative treatment, but additional catheter
      ablation is needed to treat postoperative atrial tachycardia in some cases.
      Little is known about electrophysiological characteristics or mapping techniques
      of recurrent tachycardia after total thoracoscopic surgical ablation and left
      atrial appendectomy. A 63-year-old man underwent catheter ablation of atrial
      tachycardia after total thoracoscopic left atrial appendectomy and surgical
      ablation of atrial fibrillation lasting longer than 5 years. Catheter ablation
      was performed using a three-dimensional mapping system. Electroanatomical mapping
      outside the box lesion revealed a centrifugal activation pattern with the origin
      located at the gap of the roofline, and further activation mapping inside the box
      lesion was conducted again with the reference catheter positioned at the left
      atrial posterior wall, which revealed localized reentrant atrial tachycardia.
      Atrial tachycardia was smoothly treated with activation mappings. This case
      indicated the utility of activation mappings separating outside the box lesions
      from inside the box lesions. <Learning objective: Electroanatomical mapping
      outside a box lesion might help to ablate postoperative atrial tachycardia in a
      patient undergoing surgical box isolation, and reentry localized in the left
      atrial posterior wall could be visualized using a three-dimensional mapping
      system with the reference catheter positioned at the box lesion. Confirmation of
      a completely isolated box lesion is vital, because such patients have a
      sufficiently enlarged left atrium that has the arrhythmogenicity to maintain
      atrial tachycardia.>.

PMID- 30279905
TI  - A case of hypertensive emergency, primary hypothyroidism and large pericardial
      effusion with early tamponade.
AB  - Thyroid hormones and the cardiovascular system are strongly intertwined with
      known risk of coronary disease, atrial fibrillation, and cardiomyopathy.
      Pericardial effusions are commonly seen in cases of severe hypothyroidism,
      however large to massive pericardial effusions with cardiac tamponade are
      exceptionally rare. We report a case of a patient presenting with hypertensive
      emergency and a concomitant diagnosis of primary hypothyroidism with a large
      pericardial effusion and early echocardiographic features of tamponade. Following
      pericardiocentesis, hypertension management, and thyroid replacement therapy the
      patient's symptoms improved with no recurrence of pericardial effusion. <Learning
      objective: Hypothyroidism is a common medical comorbidity with many clinical
      manifestations and cardiovascular effects including hypertension. Pericardial
      effusion is a known complication of hypothyroidism, however cases of massive
      effusion and tamponade are rare. Management of large effusions is unclear, with
      some patients treated with thyroid supplement and others requiring
      pericardiocentesis.>.

PMID- 30279906
TI  - The TNNI3 Arg192His mutation in a 13-year-old girl with left ventricular
      noncompaction.
AB  - Left ventricular noncompaction (LVNC) is a distinct cardiomyopathy that is
      morphologically characterized by a two-layered myocardium, numerous prominent
      trabeculations, and deep intertrabecular recesses communicating with the left
      ventricular cavity. We present a case report regarding the identification of a
      new mutation in TNNI3 in a patient with LVNC using next-generation sequencing. A
      13-year-old girl who had no family history of cardiac disease was hospitalized
      with dyspnea after exercise and electrocardiographic abnormalities during a
      school screening. Based on her clinical features, she was diagnosed with LVNC.
      Via genetic analysis, a TNNI3 heterozygous missense variant was identified in the
      proband. Although mutations in TNNI3 have been reported in patients with
      hypertrophic cardiomyopathy and restrictive cardiomyopathy, this is the first
      report of a mutation in this gene in a patient with LVNC. <Learning objective: We
      identified a variant in TNNI3 in a patient with isolated left ventricular
      noncompaction using next-generation sequencing (NGS). Mutations in TNNI3 have
      been reported in patients with hypertrophic cardiomyopathy and restrictive
      cardiomyopathy. The use of NGS also results in the identification of multiple
      genetic variants of unknown significance to the investigated disease.>.

PMID- 30279907
TI  - Leuconostoc species endocarditis in an intravenous drug user.
AB  - Infective endocarditis is a potentially lethal infection, which predominantly
      affects the atrioventricular valves. Rapid identification and management is
      critical to reduce morbidity and mortality in this patient population. Herein, we
      present a case of a 24-year-old man with Leuconostoc species infective
      endocarditis of the aortic valve. Disease course was complicated by several
      septic emboli to the brain, central retinal artery, and spleen. This case serves
      to remind clinicians that Leuconostoc species, which are typically not pathogenic
      to human species, can cause infective endocarditis in individuals with a history
      of intravenous drug use. <Learning objective: It is crucial that clinicians
      maintain a high index of suspicion in high-risk patients for infective
      endocarditis with Leuconostoc species, especially in the setting of positive
      blood cultures with group viridans streptococcus resistant to penicillin.
      Although cases of penicillin resistant group viridans streptococci have been
      reported, it is not common and merits further review. Leuconostoc is a Gram
      positive ovoid cocci that is intrinsically vancomycin-resistant and is typically
      non-pathogenic to the human species.>.

PMID- 30279908
TI  - Acute cardiac tamponade secondary to ruptured pericardial cyst: Case report and
      literature review.
AB  - Pericardial cysts are a rare disorder with an incidence of about 1 in 100,000,
      the majority of which are benign and incidentally identified. Pericardial cyst
      causing cardiac tamponade is an extremely rare phenomenon. The exact incidence of
      cardiac tamponade secondary to pericardial cyst is unknown. To the best of our
      knowledge limited case reports showing this association have been published. We
      have summarized cases showing this association in a tabular fashion. We present a
      case of a 36-year-old male who presented with symptoms of shortness of breath,
      chest pain, and fevers found to have ruptured pericardial cyst causing cardiac
      tamponade. <Learning objective: The majority of pericardial cysts are diagnosed
      incidentally and have benign course. Pericardial cyst causing cardiac tamponade
      is an extremely rare phenomenon. Ruptured pericardial cysts should be considered
      in the differential diagnosis of cardiac tamponade in patients with history of
      pericardial cyst. Interventions such as immediate pericardiocentesis, sternotomy,
      and surgical resection of cyst can be life-saving.>.

PMID- 30279909
TI  - An incomplete pacemaker lead fracture causing inappropriate pacing inhibition due
      to oversensing of the minute ventilation sensor pulses.
AB  - Cardiac pacemakers using rate response technologies represent the effectiveness
      of increasing the heart rate and cardiac output during exercise. Minute
      ventilation (MV) sensors are popular and estimate rates using transthoracic
      impedance by emitting very low amperage short electrical current pulses between
      the pacemaker lead tip and pulse generator. We present a case of an incomplete
      pacemaker lead fracture developing inappropriate pacing inhibition due to
      oversensing caused by the electrical current emitted by the MV sensor. A
      permanent pacemaker replacement was performed, resulting in no further abnormal
      findings such as inappropriate pacing inhibition. <Learning objective: The minute
      ventilation (MV) sensor is estimated using the transthoracic impedance by
      emitting a very low amperage and short pulses of electrical current between the
      pacemaker lead tip and pulse generator. Therefore, if a fractured lead occurs,
      the voltage from the current pulses emitted for the MV sensor might be high
      enough to be oversensed as ventricular waves. We recommend that it is necessary
      to keep in mind the possibility of a fractured lead if oversensing of the
      thoracic impedance measurement current is observed.>.

PMID- 30279910
TI  - Urgent cardiac resynchronization therapy is useful in patients with decompensated
      heart failure requiring inotropes and mechanical circulatory support.
AB  - Although cardiac resynchronization therapy (CRT) is beneficial in patients with
      heart failure (HF) and left ventricular dyssynchrony, its effectiveness has not
      been established in patients with decompensated HF on mechanical support. Here,
      we report two patients with decompensated HF depending on inotropes and intra
      aortic balloon pumping (IABP), who were rescued by urgent CRT implantations. Both
      patients had non-ischemic cardiomyopathy with wide QRS of left bundle brunch
      block. IABP could be weaned just after introducing CRT. CRT can dramatically
      improve hemodynamics even in severely decompensated HF, and thus could be
      considered when left ventricular dyssynchrony is present. <Learning objective:
      The efficacy of cardiac resynchronization therapy (CRT) for acutely decompensated
      heart failure (HF) is controversial. However, the patients with wide QRS complex
      with left bundle brunch block and non-ischemic etiology can be the candidates of
      CRT implantation in order to wean inotrope and mechanical circulatory support.>.

PMID- 30279911
TI  - Right atrium floating thrombus and bilateral pulmonary embolism in a patient with
      pancreatic pseudocyst.
AB  - Pulmonary embolism in the context of pancreatitis is a rare condition and even
      fewer cases of pulmonary embolism associated with pancreatic pseudocyst and
      chronic pancreatitis have been reported in the literature. We present the case of
      a patient diagnosed with chronic pancreatitis due to alcohol ingestion
      complicated with pancreatic pseudocyst, with no classic thrombogenic risk
      factors, who developed right atrial thrombus and massive bilateral pulmonary
      embolism. <Learning objective: Venous thromboembolism risk is present in acute
      pancreatitis or pancreatic cancer, but even chronic pancreatitis may promote
      thrombogenesis and trigger the development of a life-threatening condition such
      as pulmonary embolism. The presence of pancreatic pseudocyst may further increase
      this risk. Thromboembolism prophylaxis should be considered in patients with
      chronic pancreatitis.>.

PMID- 30279912
TI  - Dynamic left ventricular outflow tract obstruction complicated with takotsubo
      cardiomyopathy: The acute phase of takotsubo cardiomyopathy manifests latent left
      ventricular outflow tract obstruction.
AB  - Dynamic left ventricular (LV) outflow tract (LVOT) obstruction is sometimes
      complicated with takotsubo cardiomyopathy (TC). The present case involves a 70
      year-old woman with chest discomfort. Seven years earlier, transthoracic
      echocardiography revealed LVOT obstruction due to a sigmoid-shaped septum. She
      underwent urgent cardiac catheterization for suspected acute coronary syndrome.
      She was diagnosed as having TC with LVOT obstruction. After undergoing
      conservative treatment, her LV function normalized and the LVOT obstruction
      resolved. After the LV wall motion normalized, administering an intravenous
      infusion of dobutamine again provoked LVOT obstruction. In this situation, the
      presence of TC manifested latent LVOT obstruction. <Learning objective: Although
      dynamic left ventricular outflow tract (LVOT) obstruction is the important
      compication of takotsubo cardiomyopaty (TC), the mechanism of LVOT obstruction
      remains unclear. This case had latent LVOT obstruction due to sigmoid-shaped
      septum, and LVOT obstruction might be manifested in the acute phase of TC. This
      phenomenon has potential for mechanism of LVOT obstruction complicated with TC.>.

PMID- 30279913
TI  - Transcatheter occlusion of complex pulmonary arteriovenous malformations in a
      cyanotic child.
AB  - This case report presents a 16-month-old boy with isolated mild cyanosis
      diagnosed to have complex pulmonary arteriovenous malformations. Three
      dimensional computed tomography with volume rendering has provided the diagnosis,
      enabled detailed imaging, and facilitated transcatheter device occlusion of the
      complex arteriovenous malformations by vascular plugs and coils. Magnetic
      resonance of the brain revealed associated dural arteriovenous malformation.
      Genetic testing showed a missense disease-causing variant in the ENG gene that
      encodes endoglin, and the diagnosis of hereditary hemorrhagic telangiectasia was
      made. <Learning objective: The initial clinical presentation of isolated mild
      cyanosis in a child with pulmonary arteriovenous Malformations (PAVMs) has led to
      the diagnosis of hereditary hemorrhagic telangiectasia may pose a diagnostic
      challenge. The use of three-dimensional computed tomography with volume rendering
      enables the diagnosis of complex PAVMs and facilitates the planning of
      transcatheter device occlusion.>.

PMID- 30279914
TI  - Mid-axillary pacemaker re-implantation after contralateral pocket infection in an
      emaciated elderly case.
AB  - The number of implantations of cardiac implantable electrophysiological devices
      (CIEDs) has increased over the past several years. However, the aging population
      and expansion of indications for CIEDs have led to an increase in associated
      infections. We experienced a case of a 99-year-old man presenting with skin
      erosion at the pocket site, where a 6-month-old implantable pacemaker was
      replaced. He was referred for pacemaker pocket infection and presented with fever
      accompanied by pain and swelling around pacemaker generator. We could not explant
      7-year-old pacemaker leads and the patient refused to undergo either laser lead
      extraction or surgical removal. We planned to re-implant in the contralateral
      chest. However, the patient was emaciated with low body-mass-index (15.2 kg/m2),
      thus concerns arose about the possibility of tissue disruption and re-infection
      owing to thin skin and absence of sufficient subcutaneous tissue in contralateral
      subclavian region. Axillary placement of CIEDs has been adopted in patients with
      limited venous access. We applied a mid-axillary pacemaker implant procedure to
      this elderly and emaciated patient. Postoperative clinical course was uneventful.
      After discharge, no history of unexplained fever or illness was recorded. Mid
      axillary pacemaker pocket could be an alternative approach for re-implantation in
      patients with emaciated, cachexic, or limited pocket preparation. <Learning
      objective: We apply the mid-axillary pacemaker implant procedure to a
      nonagenarian with contralateral pacemaker infection to minimize the risk of skin
      disruption after implantation. This implies that implantation is possible in
      patients with emaciated or cachexic or infection of the contralateral subclavian
      pocket. Mid-axillary pacemaker pocket could be an alternative approach for re
      implantation in patients with emaciated, cachexic, or limited pocket
      preparation.> .

PMID- 30279916
TI  - Two adherent blood cysts in subvalvular apparatus of the mitral valve causing
      severe left ventricular outflow tract obstruction.
AB  - Blood cysts in the heart are often incidentally found during post-mortem
      examinations in infants, and usually do not cause clinical symptoms. They almost
      always regress spontaneously, and only a few cases of embolization or valvular
      dysfunction have been reported previously. We report a 62-year-old man who
      presented with chest discomfort and dyspnea on exertion for several years, and
      was found to have a dynamic murmur in left ventricular outflow tract (LVOT) on
      physical examination. His echocardiogram demonstrated two large blood cysts
      attached to the subvalvular apparatus of mitral valve, causing significant LVOT
      obstruction and mild to moderate mitral regurgitation. The cysts were surgically
      excised and pathology confirmed simple blood cysts. <Learning objective: To the
      best of our knowledge, this is the first reported case of twin blood cysts with
      severe left ventricular outflow tract obstruction in an adult, since most of
      these cysts either regress spontaneously in childhood or remain asymptomatic in
      adults.>.

PMID- 30279915
TI  - Evaluation of repeated progression of native coronary artery stenosis by optical
      frequency domain imaging in a patient with essential thrombocytosis.
AB  - Essential thrombocytosis (ET) is a myeloproliferative disorder with abnormal
      proliferation of the megakaryocytes and is manifested clinically by the
      overproduction of dysfunctional platelets, leading to thrombus formation.
      Therefore, the accurate evaluation of the morphological features for coronary
      stenosis and initiation of appropriate treatment may be life-saving for ET
      patients. In this report, we describe a case of the rapid development of repeated
      stenosis in the native coronary artery in an ET patient, and optical frequency
      domain imaging confirmed the etiology of the stenoses. These findings may be
      helpful for consideration of etiology and therapeutic strategy for thrombotic
      complications in ET patients. <Learning objective: Although coronary thrombosis
      could occur in essential thrombocytosis patients with particularly high platelet
      counts, strong antiplatelet therapy with the use of multiple antiplatelet agents
      together with a cytoreductive drug for maintaining peripheral platelet count
      under 60 * 104/mm3 should be considered to reduce the risk of recurrence of
      coronary events. An accurate assessment of lesion morphology and patient-tailored
      management can reduce morbidity and mortality in this population.>.

PMID- 30279917
TI  - Promising method for management of venoarterial extracorporeal membrane
      oxygenation: A case of severe heart failure successfully stabilized by "high
      flow/vasodilation method".
AB  - We report the case of a 58-year-old man with dilated cardiomyopathy who was
      hospitalized because of worsening heart failure. As his symptoms were refractory
      even with the administration of inotropes, he was given peripheral venoarterial
      extracorporeal membrane oxygenation (VA-ECMO) upon transfer to our hospital. On
      admission, serum creatinine was 2.62 mg/dL and total bilirubin 10.8 mg/dL. The
      cannulas inserted were 16-Fr for infusion and 21-Fr for drainage. When the blood
      flow was increased to 2.14 L/min/m2 to improve organ dysfunction, the aortic
      valve became continuously close with the mean arterial pressure of 85 mmHg.
      Therefore, we administrated vasodilators to decrease mean arterial pressure, or
      left ventricular afterload, which achieved opening aortic valve continuously.
      After the cannula sizes were scaled up to 18Fr for infusion and 24Fr for drainage
      to gain further blood flow, the aortic valve opened continuously and mean
      pulmonary pressure decreased. Our strategy to maintain adequate flow rate of VA
      ECMO using vasodilator, "high-flow/vasodilation method", achieved hemodynamic
      stability. Additionally, the concentration of serum creatinine and total
      bilirubin gradually decreased to within the normal range, although the patient
      succumbed 58 days after transfer to our hospital. <Learning objective:
      Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is often used as a
      first-line mechanical circulatory support in patients with severe heart failure.
      However, its management is difficult and not established. We discuss the efficacy
      and potency of our "high-flow/vasodilation method" in the management of VA
      ECMO.>.

PMID- 30279918
TI  - Adult aortic coarctation presenting with refractory heart failure and pulsation
      below the bilateral clavicle.
AB  - Adult aortic coarctation is often asymptomatic and this condition can be detected
      because of a murmur or unexplained hypertension. Here, we report an adult case of
      aortic coarctaion with heart failure and a characteristic finding of pulsation
      below the bilateral clavicle.  A 58-year-old man with refractory heart failure
      due to unknown reasons was referred to our hospital. Auscultation presented no
      murmur and high blood pressure had been treated with medicine. Interestingly,
      precise physical examination revealed the bilateral pulsation at the
      midclavicular line from the 2nd to the 5th intercostal areas. Echographic
      examination revealed the dilated vessel and arterial blood flow 1-2 cm in depth
      from the body surface at the midclavicular 2nd intercostal areas. Contrast
      enhanced computed tomography showed thoracic aortic coarctation and a well
      developed collateral circulation via the bilateral internal thoracic arteries and
      epigastric arteries. The cause of heart failure was diagnosed as aortic
      coarctation. Palliative revascularization was performed and his blood pressure
      was lowered. When we see the patients with refractory heart failure due to
      unknown reasons, pulsation below the bilateral clavicle may give us a clue to
      diagnose the "hidden" aortic coarctation. <Learning objective: We must consider
      adult aortic coarctation when we see patients with refractory heart failure.
      Although the present case did not show a cardiac murmur characteristic of aortic
      coarctation, we found out the very unique sign of pulsation below the bilateral
      clavicle. When we see patients with refractory heart failure due to unknown
      reasons, pulsation below the bilateral clavicle may give us an important clue to
      diagnose the "hidden" aortic coarctation.>.

PMID- 30279919
TI  - Novel assessment of retrospective on-demand analysis of venous thromboembolism by
      dual-layer spectral-detector CT.
AB  - Because the prognosis of pulmonary thromboembolism (PTE) will be often poor,
      early diagnosis and assessing severity at the first visit is important. A 76-year
      old man with suspected venous thromboembolism and a contrast deficit in the
      pulmonary artery (PA) was revealed by contrast-enhanced computed tomography (CT)
      imaging by dual-layer spectral-detector CT (IQon Spectral CT(r), Philips
      Healthcare, Best, The Netherlands). The lung perfusion image showed decreased
      perfusion in the culprit lesion. The dual-energy analysis of the virtual
      monoenergetic imaging showed clear visualization of deep vein thrombosis (DVT).
      In a 64-year-old man, an IQon Spectral CT(r) revealed a small contrast deficit in
      the PA. However, no perfusion abnormality was detected in the lung perfusion
      analysis. The IQon Spectral CT(r) enables the detection of lung perfusion
      abnormalities in addition to PTE. The IQon Spectral CT(r) imaging may be useful
      for the "one-stop shop" evaluation of PTE and DVT. <Learning objective: The
      prognosis of pulmonary thromboembolism (PTE) will be often poor, so early
      diagnosis and assessing severity at the first visit is important. The dual-layer
      spectral-detector computed tomography imaging for PTE, whereby the iodine map
      provided information regarding lung perfusion, whereas virtual monoenergetic
      images enabled clear visualization of deep vein thrombosis.>.

PMID- 30279920
TI  - Visceral malperfusion after thoracic endovascular aortic repair for type B aortic
      dissection in a post-abdominal aortic grafting patient.
AB  - A 69-year-old woman with a history of graft replacement for abdominal aortic
      aneurysm developed a complicated type B aortic dissection that resulted in renal
      malperfusion after thoracic endovascular aortic repair (TEVAR). The primary entry
      tear was formed at the aortic arch and the false lumen (FL) continued to the
      abdominal aorta. The distal end of the FL formed a pouch-like blind alley above
      the suture line of the bifurcated abdominal graft. The true lumen (TL) was
      compressed and caused severe limb ischemia. The right renal artery (rRA)
      originated from the FL. The patient had initially undergone emergent
      axillofemoral bypass for limb malperfusion. Three weeks later, restenosis of the
      TL caused visceral malperfusion, and a huge thrombus formed in the FL pouch.
      TEVAR expanded the TL and restored visceral vascularization. However, the
      expanded TL compressed the thrombus in the blind alley to the rRA orifice and
      caused right renal malperfusion. The history of abdominal graft replacement may
      have increased the risk of a thrombotic event after TEVAR. Primary TEVAR may have
      helped prevent thrombus formation in the FL pouch. <Learning objective: This case
      report describes visceral arterial embolism induced by endovascular aortic repair
      (TEVAR) for type B aortic dissection in a patient with prior abdominal aortic
      grafting. A huge thrombus formed in the blind pouch of the false lumen (FL) above
      the graft suture line. TEVAR expanded the true lumen and the FL thrombus occluded
      a visceral artery with FL origin. Post-graft replacement has a risk of thrombus
      formation in the FL pouch and thrombus compression in visceral arteries.>.

PMID- 30279921
TI  - A case of acute heart failure due to myocardial infiltration of mycosis
      fungoides.
AB  - Mycosis fungoides (MF) has been reported to be the most common cutaneous lymphoma
      with a good prognosis and myocardial infiltration is clinically rare. We hereby
      report a case of rapidly progressing acute heart failure due to myocardial
      infiltration by MF. Perfusion cardiac magnetic resonance imaging (MRI)
      demonstrated a massive perfusion defect in the left ventricle (LV) where multiple
      nodular enhancement areas by delayed enhancement MRI could be documented in the
      postero-lateral wall of the LV, which resulted in a deterioration of the LV
      function and mitral regurgitation. Autopsy confirmed the myocardial infiltration
      by the MF, which corresponded with the MRI findings. <Learning objective:
      Symptomatic heart failure patients with myocardial infiltration by mycosis
      fungoides (MF) have a poor prognosis because they could not undergo chemotherapy
      for primary disease. Therefore, early diagnosis is important for improvement of
      prognosis. The routine assessment of the cardiac involvement by cardiac magnetic
      resonance imaging as well as transthoracic echocardiography should be performed
      for an early recognition of myocardial infiltration even in asymptomatic MF
      patients.>.

PMID- 30279922
TI  - Long-standing persistent effects of atrial volume reduction combined with
      pulmonary vein isolation.
AB  - Although surgical left atrial (LA) volume reduction combined with mitral valve
      surgery and/or surgical ablation for atrial fibrillation has been reported to be
      effective, its long-term outcomes in the absence of mitral procedure are not well
      established. A 74-year-old man with two previous sternotomies-the first for
      pericardiectomy due to constrictive pericarditis and the second for mitral valve
      replacement with mechanical valve and tricuspid annuloplasty-presented with heart
      failure and thrombus in his giant left atrium (1291 mL), complicated by cerebral
      infarction. His electrocardiogram showed rate-controlled persistent atrial
      fibrillation. His mechanical valve was functioning well. A third atrial volume
      reduction combined with pulmonary vein isolation, without valve surgery, was
      performed. The postoperative course was uneventful, and the patient has remained
      asymptomatic with regular junctional rhythm and without any episodes of
      thromboembolism or re-dilation of LA (approximately 550 mL). His left ventricular
      filling improved with end-diastolic volume (96 mL vs 140 mL) and forced vital
      capacity (2.60 L vs 2.89 L) increased. Both remained relatively constant for 6
      years. The combination of atrial volume reduction with pulmonary vein isolation
      prevented thromboembolism, improved left ventricular filling, and continued to
      improve symptoms associated with heart failure and respiratory condition for 6
      years. <Learning objective: The long-term outcomes of surgical left atrial volume
      reduction combined with ablation for atrial fibrillation in the absence of mitral
      valve procedure are not well established. We hereby report a case of left atrial
      volume reduction combined with pulmonary vein isolation, without valve surgery,
      whose beneficial effects on symptoms associated with heart failure, particularly
      left ventricular filling, respiratory function, and stroke prevention, have
      persisted for 6 years postoperatively.>.

PMID- 30279924
TI  - Percutaneous atrial septal defect closure through femoral and transjugular
      approaches in patients with interrupted inferior vena cava.
AB  - Femoral venous approach is the classic route of percutaneous atrial septal defect
      (ASD) closure. But in patients with interrupted inferior vena cava (IVC) with
      azygos continuation the normal connection is lost rendering transcatheter
      intervention more complicated and innovative approaches should be sought.
      Transhepatic approach has been used with success but this approach is technically
      demanding and could lead to major complications. We report successful
      percutaneous secundum ASD closure in 2 patients with interrupted IVC.
      Transjugular route was used to close the secundum ASD in a 15-month-old girl.
      Percutaneous ASD closure through femoral venous route was performed in a 49-year
      old woman. We found that both these approaches of percutaneous ASD device
      occlusion can be performed with success and safety. <Learning objective:
      Interrupted inferior vena cava with azygos or hemiazygos continuation is a rare
      congenital anomaly but potentially complicates the usual percutaneous atrial
      septal defect (ASD) closure and therefore merits an accurate diagnosis before the
      procedure. Percutaneous ASD device closure can be performed with success and
      safety through femoral and transjugular approaches in patients with ostium
      secundum ASD who present with interrupted inferior vena cava.>.

PMID- 30279923
TI  - Complete healing of spontaneous coronary artery dissection extending from the
      left main trunk to the left anterior descending and the left circumflex artery.
AB  - Spontaneous coronary artery dissection (SCAD) is defined as a spontaneous
      separation of the coronary artery wall that is not iatrogenic or related to
      trauma and usually affects young women. We describe a 65-year-old woman who
      presented with SCAD extending from the left main trunk involving the left
      anterior descending artery and the left circumflex artery, and coronary artery
      bypass graft surgery was performed to treat the dissection. Coronary angiography
      performed 3 months later, showed complete angiographic healing. A conservative
      management strategy is known to be associated with spontaneous angiographic
      healing in patients with SCAD who are hemodynamically stable. Healthcare
      providers should consider SCAD among the differential diagnoses in patients
      presenting with acute coronary syndrome, particularly in women. Further studies
      are needed to establish an optimal management strategy for SCAD. <Learning
      objective: Spontaneous coronary artery dissection (SCAD) might be a cause of
      acute coronary syndrome not only in younger but also in older women. Even if the
      area of the dissection is broad, healing can be expected in future. Therefore, it
      is important to select between conservative and invasive therapy such as
      percutaneous coronary intervention or coronary artery bypass graft including
      selection of graft, i.e. saphenous vein graft and radial arteries, and internal
      mammalian arteries.>.

PMID- 30279925
TI  - Fourth mitral valve replacement in a 15-year span in a woman of childbearing age.
AB  - There is no report of four valve replacement surgeries in a woman during 15-year
      follow-up. A 23-year-old female was diagnosed at 7 years with rheumatic fever.
      She developed severe mitral regurgitation and at the same age a prosthetic valve
      was placed. In the next 15 years her mitral valve was changed 3 times because of
      clinical, echocardiographic, and histopathologic evidence of thrombosis. Her
      coagulation tests all showed infratherapeutic international normalized ratio and
      by the age of 15 years she had had an ischemic stroke with total recovery. She
      developed a normal pregnancy by the age of 19 years with no complications. This
      case exposes the complexity of the decision making that cardiologists face in
      terms of choosing the type of prosthetic valve that should be indicated in a
      woman of childbearing age. With each surgical valve replacement prognosis is less
      favorable and choosing the best therapy remains a challenge for the heart team.
      <Learning objective: Valvular heart disease remains a challenging problem due to
      anticoagulation issues. Prosthetic valvular replacements need a thorough follow
      up for anticoagulation goals. Women of childbearing age can both have mechanic
      and biologic prosthesis.>.

PMID- 30279926
TI  - Accessory and solitary main papillary muscle hypertrophy resulting in dynamic mid
      left ventricular obstruction: Contribution of multimodality imaging in
      highlighting of dynamic and structural abnormalities.
AB  - Solitary main and/or accessory papillary muscle (PM) hypertrophy may be an
      uncommon type of hypertrophic cardiomyopathy that does not meet all the usual
      criteria. The dynamic intraventricular obstruction related to this PM hypertrophy
      can be deleterious with an important clinical impact on patients. The mechanisms
      of such obstruction attracted a lot of attention in order to propose an
      appropriate treatment. We report a case of a 36-year-old man presenting with a
      chief complaint of progressively worsening exertional dyspnea. He had
      demonstrated labile systolic murmur for more than 3 years. Rest echocardiography
      revealed coexistence of a solitary main PM hypertrophy and additional accessory
      PM with no left ventricular outflow tract or mid ventricle obstructions. The
      patient underwent exercise stress echocardiography unmasking severe mid-ventricle
      obstruction (peak systolic gradient at exercise of 100 mmHg). There was no
      obvious parietal hypertrophy elsewhere. Cardiac magnetic resonance imaging
      provided us with anatomical arguments that could explain the dynamic process of
      obstruction. In fact, multimodality imaging has a determinant role in the
      screening of spatial configuration and structural abnormalities of PMs in order
      to avoid the misinterpreting of some atypical presentations of hypertrophic
      cardiomyopathy. <Learning objective: Solitary main and/or accessory papillary
      muscle (PM) hypertrophy is an uncommon type of hypertrophic cardiomyopathy:
      hypertrophy concerns only the PM and spares the other parietal left ventricle
      segments. Multimodality imaging has a crucial role in the characterization of PM
      morphology and their incrimination in the pathological process of dynamic
      obstruction. Surgical treatment depends on the concerned PM, its extent to the
      mitral leaflet or the septum, or both, and the severity of hypertrophy.>.

PMID- 30279927
TI  - T-wave alternans in a case with systemic lupus erythematosus-related myocarditis.
AB  - A 42-year-old woman presented with fever, dyspnea, lower-leg edema, significant
      pulmonary congestion, pleural effusion, and severely reduced left ventricular
      contractions. She was resistant to treatment for heart failure, including
      catecholamines, furosemide, phosphodiesterase III inhibitors, and human atrial
      natriuretic peptide, and antibiotics failed to reduce her inflammation. She had
      renal dysfunction and hypocomplementemia and was positive for anti-nuclear and
      anti-ds-DNA antibodies. The patient was diagnosed with myocarditis and pleurisy
      associated with systemic lupus erythematosus (SLE). Prednisolone administration
      improved her general condition, reducing inflammation and improving left
      ventricular function. On day 1, an electrocardiography (ECG) revealed a T-wave
      inversion similar to a T-U complex configuration in leads II, aVF, and V3-6. By
      day 8, however, ECG showed prolonged corrected QT (QTc) and T-wave alternans
      (alternating beat-to-beat T-wave patterns) in lead V3-6. Careful ECG monitoring
      should be used to identify potentially fatal ventricular arrhythmias during the
      recovery phase of SLE-related myocarditis. <Learning objective: This was a case
      of significant T-wave alternans (TWA) during recovery from systemic lupus
      erythematosus (SLE)-related myocarditis. Fatal ventricular arrhythmia appears to
      be a risk during recovery from myocardial damage caused by SLE. Up to now, there
      have been no published case reports of TWA during this period. Patients with
      myocarditis should be carefully monitored for arrhythmia, even after ventricular
      function and inflammation have improved with prednisolone therapy.>.

PMID- 30279929
TI  - The utility of atrial overdrive pacing during catheter ablation of premature
      ventricular contractions originating from the posterior-superior process of the
      left ventricle.
AB  - A 76-year-old man presented with frequent premature ventricular contractions
      (PVCs). The electrophysiological findings revealed the origin of the PVCs was in
      the posterior-superior process of the left ventricle (PSP-LV), which is
      anatomically adjacent to the infero-medial aspect of the right atrium (RA). After
      a failed ablation from the LV, ablation in the RA eliminated the PVCs. During
      additional ablation, the atrio-his (AH) interval was monitored by atrial
      overdrive pacing, and ablation was terminated immediately after the AH interval
      prolonged to 174 ms. We believe that the atrial overdrive pacing was useful for
      monitoring the AH interval to prevent atrioventricular block during ablation of
      PVCs from the PSP-LV. <Learning objective: PVCs from posterior-superior process
      of the LV (PSP-LV) could be eliminated by radiofrequency ablation at the
      posterior-septum of the RA. It is important to closely examine the AH interval in
      order to prevent any atrioventricular block during the ablation of PVCs
      originating from the PSP-LV. Atrial overdrive pacing is helpful to monitor the AH
      interval during the ablation of PVCs originating from the PSP-LV.>.

PMID- 30279928
TI  - Restoration of vision by endovascular revascularization in Takayasu arteritis: A
      case series.
AB  - Takayasu arteritis (TA) is a rare, inflammatory vasculitis affecting aorta and
      its branches. Stenotic occlusive lesions of multiple arch arteries can cause
      severe cerebral ischemia leading to impaired vision. We present three consecutive
      young patients of TA with severe diminution of vision on upright posture, where
      we attempted restoration of sight by improving cerebral blood flow by
      percutaneous endovascular revascularization. All three patients could be
      successfully revascularized with substantial improvement in vision. There was no
      complication. On follow up, one patient developed recurrence of visual symptoms
      due to restenosis, which was successfully treated by cutting balloon angioplasty.
      The objective of this case series is to highlight the role of endovascular
      techniques in reversing visual loss in such situations. <Learning objective:
      Takayasu arteritis (TA) is an inflammatory vasculitis that can affect arch
      arteries leading to near complete obliteration and often disabling symptoms such
      as loss of vision. This case series (3 cases) shows that stent-supported
      angioplasty is a minimally invasive technique which is safe and effective in
      restoring impaired vision caused by severe cerebral hypoperfusion in TA.>.

PMID- 30279930
TI  - Assessment of myocardial fibrosis using T1-mapping and extracellular volume
      measurement on cardiac magnetic resonance imaging for the diagnosis of radiation
      induced cardiomyopathy.
AB  - Radiation-induced heart disease (RIHD) is a serious side effect of thoracic
      radiation therapy (RT) and is associated with significant morbidity and
      mortality. Radiation-induced cardiomyopathy (RICM) is one of the manifestations
      of RIHD, which represents with left ventricular (LV) systolic and diastolic
      dysfunction due to myocardial fibrosis. Although the diagnosis of RIHD is
      challenging and is generally an exclusion diagnosis, multimodality imaging
      including echocardiography, cardiac computed tomography and cardiac magnetic
      resonance (CMR) imaging could help the diagnosis. Herein, we report a case of 70
      years-old male, who had been treated with chemo-radiation therapy for early
      esophageal cancer, was suffered from medically refractory heart failure due to
      severely reduced LV systolic function and constrictive pericarditis 8 years after
      chemo-radiation therapy. Although no gadolinium-enhancement (LGE) was detected on
      CMR, T1 mapping depicted increased extracellular matrix volumes of 45%, which
      suggested global myocardial fibrosis. Histopathological analysis by
      endomyocardial biopsy (EBM) revealed marked degeneration of myocytes and
      interstitial fibrosis, while vacuolation in myocytes which is characteristics of
      chemotherapy induced cardiomyopathy was not specific by electron microscopy.
      Therefore, we diagnosed that the present case was likely to the RICM. <Learning
      objective: RICM is characterized by inflammation followed by the development of a
      diffuse, patchy interstitial fibrosis of the myocardium, which is usually
      obtained either by EBM or at autopsy. Native and post-contrast T1-mapping by CMR
      enables to estimate extracellular volume (ECV), which is believed to be increased
      as a result of diffuse myocardial fibrosis. The assessment of myocardial fibrosis
      using ECV should be useful for early detection of myocardial damage due to RT,
      and which probably taking place of EBM.>.

PMID- 30279931
TI  - Brugada syndrome unmasked by malaria-induced fever.
AB  - Brugada syndrome is typically an autosomal dominant genetic disorder with
      variable expression, characterized by three specific electrocardiogram (ECG)
      patterns. While Type I Brugada ECG pattern is used as a classic marker for the
      disease, it is generally masked from ECG except in special cases such as malaria
      induced fever. This vignette highlights a unique clinical scenario that can lead
      to the unmasking of Brugada type 1 pattern. <Learning objective: Brugada syndrome
      is associated with ventricular arrhythmias which if left untreated can result in
      syncope or premature death. Early intervention involving lifestyle modifications
      and recommendation of implantable defibrillator is based on diagnosis. Yet,
      Brugada syndrome is hard to detect from an electrocardiogram (ECG) alone. Still
      there are certain circumstances that unmask the Brugada syndrome ECG pattern.
      This case report provides one clinical scenario leading to the incidental
      unmasking of Brugada syndrome.>.

PMID- 30279932
TI  - Improved hemodynamics following endovascular treatment for acquired aortic
      coarctation: A case report.
AB  - A 38-year-old man underwent surgical repair of a type A aortic dissection. After
      aortic surgery, his left ventricular ejection fraction was progressively reduced
      from 65% to 15%, causing a refractory low cardiac output depending on the
      intravenous inotropes. There was a luminal stenosis of the descending aorta due
      to enlarged pseudolumen. The peak-to-peak pressure gradient at the stenosis was
      25 mmHg, which was thought to contribute to the systolic dysfunction. He
      underwent thoracic endovascular aortic repair (TEVAR) with the use of a bare self
      expanding stent. After TEVAR, the peak-to-peak pressure gradient was decreased to
      9 mmHg, resulting in hemodynamic improvement. <Learning objective: A case of
      refractory heart failure with severe impairment of left ventricular contractility
      aggravated by excessive left ventricular afterload due to a luminal stenosis in
      the descending aorta after surgical repair for type A aortic dissection was
      presented. Endovascular treatment for dilation of the stenosis contributed to the
      improved hemodynamics.>.

PMID- 30279933
TI  - Trans-catheter aortic valve implantation without contrast using the Lotus
      mechanically-expanded heart valve.
AB  - Trans-catheter aortic valve implantation (TAVI) has become an established
      treatment for inoperable and high-surgical risk patients with severe, symptomatic
      aortic stenosis (AS). Post-procedural acute kidney injury (AKI) is a frequent
      complication following TAVI and is associated with increased mortality. Patients
      with pre-existing chronic renal impairment are at particularly high risk. The
      etiology of post-TAVI AKI is multi-factorial, but the principal procedural issues
      are contrast-induced nephropathy, and renal hypoperfusion secondary to intra
      procedural hypotension. We report a case of a TAVI in an 80-year-old patient with
      severe AS and significant chronic kidney disease (CKD), which was carried out
      without the use of contrast and with minimal procedural hypotension. Pre
      procedural imaging was carried out using 3D trans-esophageal echocardiography
      (TEE) rather than computed tomography (CT) to avoid contrast administration. The
      Lotus valve (Boston Scientific, Marlborough, MA, USA) was chosen due to a number
      of design features which minimize both the need for contrast injection and
      procedural hypotension during valve positioning and deployment. The procedure was
      carried out successfully and produced an excellent result with no decline in
      renal function. We believe that the approach of using TEE and the mechanically
      expanded Lotus valve illustrates an important therapeutic approach in patients
      with severe CKD. <Learning objective: Post-procedural acute kidney injury (AKI)
      is a frequent complication following trans-catheter aortic valve implantation
      (TAVI), and is associated with increased mortality. The principal procedural
      issues are contrast-induced nephropathy and intra-procedural hypotension. Our
      case report demonstrates how TAVI can be performed with zero contrast and
      minimization of procedural hypotension, facilitated by the use of trans
      esophageal echocardiography and the mechanically-expanded Lotus valve. This
      approach should only be used in exceptional circumstances, but can be
      particularly relevant for patients with pre-existing chronic renal impairment,
      who are at increased risk of post-TAVI AKI.>.

PMID- 30279935
TI  - Left subclavian and right femoral vein thrombosis in a pregnant patient with
      antithrombin deficiency.
AB  - Pregnancy is well-known risk factor for deep vein thrombosis (DVT), which usually
      occurs during the third trimester and in the left-sided lower extremity. We
      present a case of left subclavian and right femoral vein thrombosis in a pregnant
      woman with a gestational age of 10 weeks. A 39-year-old woman visited the
      emergency department complaining of acute pain and swelling of the left upper arm
      and right lower extremity. She showed swelling of the left upper arm and right
      lower extremity and a low antithrombin level of 40%. Ultrasound examination
      showed right femoral and left subclavian vein thrombosis. Her DVTs were treated
      with unfractionated heparin. Five months later, she received a cesarean delivery
      with intravenous unfractionated heparin and antithrombin replacement to prevent
      DVT, and she successfully gave birth. A genetic test for antithrombin deficiency
      confirmed hereditary antithrombin deficiency. DVT during pregnancy can occur in
      an upper extremity and at multiple sites. An undiagnosed coagulation disorder
      magnifies the risk of DVT in pregnant patients. We should examine all extremities
      for which there are complaints of pain and swelling with suspicion of DVT and
      consecutively search for an underlying coagulation disorder in pregnant patients
      with unusual clinical features of DVT. <Learning objective: Deep venous
      thrombosis (DVT) during pregnancy can occur in an upper extremity and at multiple
      sites. An undiagnosed coagulation disorder magnifies the risk of DVT in pregnant
      patients. We should examine all extremities for which there are complaints of
      pain and swelling with suspicion of DVT and consecutively search for an
      underlying coagulation disorder in pregnant patients with unusual clinical
      features of DVT.>.

PMID- 30279934
TI  - Successfully treated eosinophilic granulomatosis with polyangiitis relapse
      presenting as myocarditis and followed by multimodality imaging.
AB  - A 60-year-old man with eosinophilic granulomatosis with polyangiitis (EGPA),
      which was diagnosed 12 years earlier and managed with prednisolone, was admitted
      to our hospital because of dyspnea and paresthesias in both hands. Laboratory
      test revealed peripheral eosinophilia along with elevated troponin T and brain
      natriuretic peptide (BNP). The patient's clinical picture was consistent with
      myocarditis and relapse of EGPA. Endomyocardial biopsy showed marked infiltration
      of eosinophils in myocardium, which confirmed relapse of EGPA with myocarditis.
      Thallium-201 and iodine-123-beta-methyl iodophenyl pentadecanoic acid dual single
      photon emission computed tomography (TL-BMIPP SPECT), as well as cardiac magnetic
      resonance imaging (CMR), also confirmed cardiac involvement. The patient was
      treated with methylprednisolone and improved dramatically. CMR and TL-BMIPP SPECT
      performed after discharge showed improvement of abnormal lesions, while anomalies
      detected by these modalities remained. This is a case of EGPA relapse presenting
      as myocarditis despite treatment with prednisolone. <Learning objective: Cardiac
      involvement and relapse are frequent in eosinophilic granulomatosis with
      polyangiitis patients. Patients should be screened and monitored carefully for
      cardiac involvement during follow-up by multimodality imaging.>.

PMID- 30279936
TI  - Handball Research: State of the Art.

PMID- 30279937
TI  - Systematic Review and Meta-Analysis on Proximal-to-Distal Sequencing in Team
      Handball: Prospects for Talent Detection?
AB  - The proximal-to-distal sequence has previously been discussed in the light of
      performance and injury prevention. Sports biomechanics literature in general, and
      in team handball in specific, has claimed to be of importance to inform coaches
      on what constitutes a 'good' technical performance. However, hitherto no
      prospective studies exist on how this information may be used and this may in
      part be due to the general small sample sizes. We therefore performed a
      systematic review and meta-analysis of proximal-to-distal sequencing in team
      handball throwing motions. A total of fourteen articles were included in the
      systematic review. Meta-analyses were performed for the timing of maximal angles
      and angular velocities as well as initiation of joint angular velocities in the
      penalty throw, the standing throw with run-up and the jump shot of experienced
      team handball players. For the initiation of joint angular velocities, the
      overall sequence was estimated to start with pelvis rotation, followed by trunk
      rotation, trunk flexion, shoulder internal rotation and elbow extension. For
      maximal velocities, the sequence started with pelvis rotation, followed by trunk
      rotation, trunk flexion, elbow extension, and shoulder internal rotation (post
      ball release). The obtained results were discussed in the light of talent
      identification purposes. Limitations to individual study methodology and of the
      present meta-analysis were also discussed. Much more research will be necessary,
      but at the very least, this review can provide a starting point for evidence
      based discussions between movement scientists and team handball coaches to
      include proximal-to-distal sequencing as a measure of coordination to gauge early
      onset of talent.

PMID- 30279938
TI  - Influence of Physical Aspects and Throwing Velocity in Opposition Situations in
      Top-Elite and Elite Female Handball Players.
AB  - The relationship between anthropometric and physical characteristics of female
      handball players and throwing velocity is considered an important factor in
      handball performance. The aim of this study was to examine key differences in
      anthropometric and fitness characteristics between top elite and elite female
      players competing in the first Spanish handball league. A total of 89 players
      from the first Spanish handball league were divided into two groups, top elite
      (38) and elite (51) players, and assessed for anthropometric and fitness
      characteristics (throwing velocity, vertical jump and hand grip strength). A
      Student's t-test was used to determine whether a statistically significant
      difference between the two different levels of play occurred. Significant
      differences were found in age, body height, body mass, arm span, muscle mass,
      different girths (tensed and flexed arm, forearm, wrist, ankle), dominant hand
      width and length, different breadths (biacromial, bitrochanteric, bistyloid
      breadth and biepicondylar humerus) and fitness characteristics (hand grip
      strength and throwing velocity for different positions). Top elite players
      compared to elite players showed differences in anthropometric characteristics
      which were mainly located in the upper limbs and mostly were nonmodifiable
      aspects by training. Furthermore, the best players were able to maintain a high
      throwing velocity in different tactical situations.

PMID- 30279939
TI  - Relative Age Effect and the Re-Selection of Danish Male Handball Players for
      National Teams.
AB  - The relationship between the date of birth and expertise in various sports among
      both elite and youth level athletes is well established, and known as the
      relative age effect (RAE). However, new results in for example Canadian Hockey
      and British cricket and rugby have indicated a reversal of RAE among selected
      talents where the youngest athletes are more likely to remain selected than their
      older peers. As such, RAE may therefore depend on the age and the level of
      competition. The purpose of this study was therefore to analyse RAE from the
      youth to senior national level in a sample of successful Danish male national
      teams. The sample included 244 players from Danish under-19, under-21 and senior
      national levels. These players have been part of successful teams, winning 18
      medals at 24 youth European and World championships and 8 medals during 12 years
      at the senior level. The results showed a significant RAE on both youth and
      national levels. However, RAE was less marked from the under-19 to under-21 and
      further to the senior national level. Results show that at the national youth
      level talent selection favours the relatively older players, of whom a larger
      proportion fails to be re-selected to the senior level compared to their younger
      peers. RAE appears to play a central and reversing role in the identification and
      re-selection in Danish male handball. The results also show that the presence of
      both a constant and constituent year structure affects RAE, even when introduced
      at late adolescence.

PMID- 30279940
TI  - Effect of Inspiratory Muscle Training on Performance of Handball Athletes.
AB  - Inspiratory muscle training (IMT) is a strategy that has been used to improve
      performance in different sports modalities. This study investigated the effects
      of an IMT program on respiratory muscle strength and resistance as well as
      aerobic physical performance (PP) of handball athletes. Nineteen 20 +/- 3 year
      old male athletes were allocated into an experimental (EG, n = 10) or a placebo
      group (PG, n = 9). Their respiratory muscle strength was evaluated by measuring
      the maximum inspiratory and expiratory pressures (MIP and MEP), muscular
      respiratory resistance by maximum voluntary ventilation (MVV) and aerobic PP by
      the cardiopulmonary exercise test. The study was designed to evaluate the effects
      of a 12-week IMT program with five sessions a week. A significant difference was
      observed in the pre and post IMT values of the MIP (170 +/- 34 to 262 +/- 33
      cmH2O) and MEP (177 +/- 36 to 218 +/- 37 cmH2O) in the EG, and MIP (173 +/- 45 to
      213 +/- 21 cmH2O) in the PG, with a large effect size for the MIP, when the
      groups were compared. MVV showed a significant increase (162 +/- 24 to 173 +/- 30
      L) in the EG, with a small effect size. There was a significant difference in
      maximum oxygen uptake (54 +/- 8 to 60 +/- 7 ml/kg/min) in aerobic PP. Oxygen
      uptake at the respiratory compensation point (RCP) (46 +/- 6 to 50 +/- 5
      ml/kg/min), with a moderate effect size for both variables, was observed in the
      EG after IMT. We concluded that IMT provided a significant increase in
      respiratory muscle strength and resistance, contributing to increased aerobic PP
      in the EG, which suggests that IMT could be incorporated in handball players'
      training.

PMID- 30279941
TI  - Foul or No Foul? Effects of Permitted Fouls on the Defence Performance in Team
      Handball.
AB  - Attacking phases in team handball are highly dynamic, characterized by fast
      movements and a high frequency of fast passes with the aim to score a goal.
      Consequently, the opposing/defending team tries to prevent successful offensive
      actions by restraining the offensive opportunities and the probabilities of
      scoring a goal. According to the rules, defensive players are allowed to use body
      contact (e.g. with bent arms) to get in and keep their optimal defending
      position. If such a contact is not in line with the rules (e.g. clutching or
      pushing) and results in a turnover of ball possession, a foul is called and a
      free-throw awarded. However, there is a lack of research answering the question
      if a permitted foul (without personal sanction) is an effective way to increase
      the probability of defending the own goal successfully, because afterwards the
      attacking team keeps possession of the ball. Thus, we investigated 1052 attacking
      phases during games at the elite level to verify whether fouls committed by a
      defender influenced successful attacking (goal vs. no goal). It was found that
      when the attack was interrupted by a permitted foul, 50.60% of the attacks ended
      with a goal. Yet, when no foul was committed, only 47.09% of the attacks ended
      with a goal, however, the analysis revealed that this difference was not
      significant. Therefore, we concluded that neither a strategy of stopping
      offensive actions by body contact nor avoiding fouls and focusing only on
      intercepting the ball were favourable solutions in successful defending in team
      handball. It seems effective to implement a defence strategy with clearly defined
      fouling zones and situations, to deal with the tactical possibility of permitted
      fouls in handball. This idea and further considerations are discussed for sports
      practice.

PMID- 30279942
TI  - Performance and Home Advantage in Handball.
AB  - The main objective of this research was to delve into the concept of playing
      handball at home from a classical perspective of previous studies. The emergence
      of regularities or certain patterns of play can be explained by the location of
      matches. Through an observational methodology and a nomothetic, monitoring and
      multidimensional design, thirty-nine European elite handball matches were
      selected (N = 39). A mixed 'ad hoc' registration system was designed. Records
      were made of the last three minutes of home and visiting games of which images
      were available. Two observers with observational methodology experience
      participated in the study. The quality of the records was dealt with in an
      intraobserver and interobserver way. Two different techniques were applied for
      the treatment of the data: a) detection of behavioral patterns by Theme (p <
      .005) (Magnusson, 2000) and b) Chaid decision trees (p < .05) using SPSSv.24. The
      results showed the existence of T-patterns according to the location (different T
      patterns: home: 1085; away: 1242) of the matches. The categories most involved in
      effective launches were unveiled. On the other hand, the Chaid model also showed
      the effect of location (p < .001): home-win (node 9) (n = 149, 69%), away-win
      (node 10) (n = 15, 16%) in handball. Crossing analysis offered enriched
      interpretations to advance in the home advantage concept. From this study,
      guidelines can be drawn that may help handball coaches to build training tasks as
      differences in behavioral patterns between home or away play in handball were
      identified. Thus, designing tasks considering a match location has requires
      specificity.

PMID- 30279943
TI  - The Relationship Between Early and Senior Level Participation in International
      Women's and Men's Handball.
AB  - International competitions at the youth elite level have become an important part
      of attempts to identify, foster and develop sporting talent. However, sports
      science scholars disagree strongly about the value and importance of such
      competitions because little is known about the relationship between early
      performance, at both the team and individual level, and later success in adult
      elite sports. The first aim of this study was therefore to explore the
      relationship between international match experience at the youth international
      team level and subsequent match experience at the junior and the senior
      international team levels. The second aim of this study was to explore the
      relationship between youth national team results and subsequent junior and senior
      national team results in international competitions. The individual-level
      analysis was based on official match participation statistics of all Norwegian
      handball players with either youth, junior and/or senior national team experience
      (n = 657) between the years 1993 and 2017. The team level analysis was based on
      team result rankings from the handball European and World Championships at the
      youth, junior and senior national team levels during this period. Statistical
      analysis at the individual level showed a significant difference between those
      handball players who did and did not have international match exposure at the
      youth and junior levels, and the number of matches they played at the senior
      international team level. No to weak correlations were found between the number
      of matches played at the youth, junior and senior international team levels.
      Statistical analysis at the team level showed a strong correlation between result
      rankings at the youth, junior and senior international team levels. Collectively,
      these findings suggest that having youth and junior international experience is
      strongly associated with the number of matches played at the senior international
      level. However, the number of matches played at the youth and junior
      international levels does not appear to determine success or predict which
      players will or will not achieve success at the senior international level.

PMID- 30279944
TI  - Differences in Speed and Power Capacities Between Female National College Team
      and National Olympic Team Handball Athletes.
AB  - The aim of this study was to compare and examine differences in several
      neuromuscular assessments between female national Olympic team (Rio-2016) and
      national college team handball players (2015-Gwangju Summer Universiade). Twenty
      eight elite female handball players of the national Brazilian Olympic (n = 12)
      and college (n = 16) teams participated in this study. The Olympic and college
      athletes performed the following speed-power tests assessing mean propulsive
      power (MPP) in loaded jump squat (JS) and bench press (BP) exercises, unloaded
      squat and countermovement jumps (SJ and CMJ), sprint performance over 5-, 10-,
      and 20-m, and change of direction ability in a standard Zig-zag test and a T
      Test. The differences between Olympic and college team performances in all
      variables were analyzed using the magnitude-based inference. The Olympic group
      presented likely higher performances in the SJ, CMJ, and MPP JS and very likely
      higher performances in the MPP BP and T-Test than the college group. The
      differences in the linear sprint velocity in 5-, 10-, and 20-m tests as well as
      in the Zig-zag test were all rated as unclear. These findings may have
      substantial implications for the development of effective strength-power training
      and testing strategies in elite handball. In addition, coaches and researchers
      can use these data to create efficient talent identification programs for youth
      handball players.

PMID- 30279945
TI  - Changes of Strength and Maximum Power of Lower Extremities in Adolescent Handball
      Players During a Two-year Training Cycle.
AB  - The aim of the study was to investigate changes of strength and power of the
      lower extremities in adolescent handball players during a two-year training
      cycle. Thirty-one male handball players (age 16.0 +/- 0.2 years, body mass 81.4
      +/- 9.7 kg, body height 188.2 +/- 6.4 cm) took part in this study. All tests were
      conducted three times at the beginning of a one-year training programme. The
      maximum joint torque (JT) of flexors and extensors of the elbow, shoulder, hip,
      knee and trunk was measured under static conditions. Power of lower extremities
      was assessed with a repeated sprint ability (RSA) test on a cycloergometer and
      jump tests: akimbo counter-movement jump (ACMJ), counter-movement jump (CMJ) and
      spike jump tests on a force plate. Peak power (PP) increased from 914.8 +/- 93.9
      to 970.0 +/- 89.2 and 1037.8 +/- 114.4 W (p < 0.05) following the RSA test
      results. Maximum power increased significantly (p < 0.05) in ACMJ (1951.9 +/-
      359.7 to 2141.9 +/- 378.5 and 2268.5 +/- 395.9 W) and CMJ tests (2646.3 +/- 415.6
      to 2831.2 +/- 510.8 and 3064.6 +/- 444.5 W). Although significant differences in
      JT (p < 0.05) were observed during the two year period, their values related to
      body mass for the lower right extremity, sum of the trunk and sum of all muscle
      groups increased significantly between the first and the second measurement (from
      13.7 +/- 1.8 to 14.58 +/- 1.99 N.m.kg-1, from 9.3 +/- 1.5 to 10.39 +/- 2.16
      N.m.kg-1, from 43.4 +/- 5.2 to 46.31 +/- 6.83 N.m.kg-1, respectively). The main
      finding of the study is that PP in the RSA test and maximal power in the ACMJ and
      CMJ increase in relation to training experience and age in the group of youth
      handball players.

PMID- 30279946
TI  - Muscle Strength Variations of Knee Joint Muscles in Elite Female Handball Players
      after Pre-Season Conditioning.
AB  - Monitoring seasonal variations in strength performance and the relative risk of
      injury indicators related to strength of hamstring (H) and quadriceps (Q) in
      female elite athletes is beneficial for the training process. The aim of this
      study was to examine and compare the level of muscle strength, the conventional
      ratio (HCONC/QCONC) as well as two functional and strength ratios reflecting the
      movement of knee extension (HECC/QCONC) and flexion (HCONC/QECC), and the
      bilateral percentage strength deficit (BSD) in elite female handball players. The
      concentric and eccentric isokinetic peak torque was measured at an angular
      velocity of 60 degrees /s on three occasions (in-season cessation, 4 weeks of
      rest followed by 4 weeks of individual conditioning and 6 weeks of group
      conditioning) in eleven female handball players (age: 23.1 +/- 3.5 years, body
      height: 1.73 +/- 0.6 m). According to ANOVA results, the BSD of H muscles in the
      concentric mode decreased between the in-season cessation and the end of the pre
      season, and HCONC/QCONC increased at the beginning of the pre-season and at the
      end of the pre-season in comparison with inseason cessation measurement. The
      effect size analyses showed that the off-season rest followed by 10 weeks of the
      conditioning programme increased Q and H strength in comparison with the previous
      season with a large effect. Coaches should include progressive conditioning in
      the pre-season phase to decrease the bilateral strength deficit and to support
      further conditioning development.

PMID- 30279947
TI  - Diurnal Variations in Physical Performance: Are there Morning-to-Evening
      Differences in Elite Male Handball Players?
AB  - The purposes of this study were to determine: 1) morning-to-evening differences
      in physical performance with and without a ball; and 2) associations between
      sleep outcomes (duration and quality) and physical performance in handball
      players. Sixteen elite, male handball players (25.4 +/- 5.8 yr, 94.0 +/- 7.4 kg,
      193.5 +/- 7.5 cm) completed physical performance tests without a ball (a zig-zag
      test assessing closed-skill agility, linear sprints, and countermovement (CMJ)
      and squat jumps) and with a ball (a zig-zag test and linear sprints) in the
      morning and evening. In addition, sleep quality and quantity during the night
      before testing were obtained using self-reported measures. Superior physical
      performance was evident in all tests during the evening compared to the morning
      hours (p < 0.003). Specifically, jump height was moderately (effect size (ES) =
      0.73 to 1.02) higher during the evening. Similarly, moderate (ES = 1.17) and
      large (ES = 1.67) improvements in zig-zag test performance were apparent during
      the evening with and without the ball, respectively. Also, large to very large
      (ES = 1.29 to 2.09) increases in sprint performance with and without the ball
      were evident in the evening. No significant correlations (p > 0.05) were apparent
      between sleep duration and quality and physical performance in both the morning
      and evening sessions. Diurnal variations in physical performance were apparent in
      elite male handball players with enhanced performance with and without the ball
      in the evening compared to morning hours. These findings indicate that morning-to
      evening differences in physical performance should be considered when developing
      conditioning plans or preparing for competition in handball.

PMID- 30279949
TI  - Effects of Short-Term Plyometric Training on Physical Performance in Male
      Handball Players.
AB  - The aim of this study was to compare the effects of plyometric and jump training
      on physical performance in young male handball players. Twenty-six young male
      handball players were divided into two sub-groups to perform a five-week pre
      season training programme supplemented with two ground-reactive protocols with an
      equal number of jumping exercises referred as to ground contacts: plyometric
      training (PLY; n = 14) and standard jump training (CON; n = 12). Before and after
      training, repeated sprint ability (RSA), jumping ability (JA), maximal oxygen
      uptake (VO2max) and aerobic power at the anaerobic threshold (PAT) were measured.
      A two-factor analysis revealed significant time effects with improvements in fat
      mass (p = 0.012), maximal power during the incremental cycling test (p = 0.001)
      and PAT (p < 0.001), power decline (PDEC) and maximal power (Pmax) in the 5th
      repetition (p < 0.05 and p < 0.01, respectively). The training-induced changes in
      absolute and relative peak power in the RSA test and absolute VO2max approached
      significance (p = 0.06, p = 0.053 and p = 0.06). No intervention time * exercise
      protocol effects were observed for any indices of JA, RSA and aerobic capacity. A
      five-week pre-season conditioning programme supplemented with only 15 sessions of
      plyometric exercise did not induce any additional benefits, compared to a matched
      format of standard jump training, in terms of improving jumping performance and
      maximal power in the RSA test. Aerobic capacity and the fatigue index in RSA were
      maintained under these two training conditions.

PMID- 30279950
TI  - Modification of Strength Training Programs in Handball Players and its Influence
      on Power During the Competitive Period.
AB  - A high level of muscle power is necessary for the effective use of technique
      during handball competitions. The presented research concentrated on comparing
      the effectiveness of two training modes directed towards the development of
      muscle power - plyometric and traditional strength training. Furthermore, we
      evaluated whether resistance training performed twice a week was sufficient to
      guarantee an increase in muscle power of handball players. We also investigated
      whether strength training designed according to the "waving" model (one training
      session per week oriented towards the development of maximal strength and one
      towards the development of power) was sufficient to increase muscle power in
      handball players. The study included 28 professional handball players who were
      divided into 3 groups: Group 1 subjected to additional strength training (8
      individuals), Group 2 subjected to traditional plyometric training (8
      individuals) and Group 3 following standard training (12 individuals). Research
      was conducted at the beginning and at the end of the 1st round of competitions
      and consisted of the following measurements: CMJ (countermovement jump) and SJ
      (squat jump), a 10-s trial on a cycle-ergometer and ball-throwing velocity.
      Analysis of the results showed that both the plyometric and strength training
      programs induced a statistically significant increase in jumping height and
      generated power during the CMJ. The group subjected to additional strength
      training achieved greater increases in CMJ power than the group carrying out
      plyometric training, which in case of the CMJ peak power turned out to be
      statistically significant (p < 0.05). Different results were obtained when
      studying changes in the flight speed of the thrown ball; the group undergoing
      plyometric training registered minor increases (significant in the standing throw
      ), and there were decreases in the flight speed of the thrown ball (significant
      in the leaning back throw) in the group following the traditional strength
      training program.

PMID- 30279948
TI  - The Relationship Between Handball Players and Alcohol and Smoking Habits.
AB  - Recent studies have revealed that sport activity is a protective factor regarding
      smoking, but a risk factor for alcohol abuse. Considering these findings, it is
      necessary to investigate the occurrence of substance misuse. Sports that are
      associated with a substantial amount of physical/mental stress are very
      interesting from the perspective of substance misuse (e.g., handball). This
      research was performed to more closely study the population engaged in handball
      regarding the risk for alcohol and/or tobacco consumption. The sample of
      respondents consisted of 150 senior handball players who were members of 9 first
      league handball clubs from Croatia and abroad. The respondents were grouped into
      sub-samples according to sex, age, experience, the number of weekly training
      sessions and their social environment (clubs). Alcohol consumption data were
      obtained using the AUDIT questionnaire. The differences between groups were
      tested using the Kruskal-Wallis and Mann-Whitney U tests. The study revealed that
      handball players engaged in alcohol misuse, and they were grouped in the harmful
      drinking category (AUDIT score, 16-19 for all groups). Regarding tobacco product
      consumption, the risk groups were women (who smoked significantly more than men,
      MWU test: Z = 3.30. p < 0.001), handball players with less experience (who smoked
      significantly more than experienced players, MWU test: Z = 3.68, p < 0.001).
      Borderline significance was observed for the impact made by social environments,
      and age was not a significant predictor of tobacco consumption. Regarding alcohol
      consumption, the highest hazard group were national handball players, who drank
      much more than foreign players did (MWU test: Z = 2.04, p = 0.04); however, sex,
      age, experience and training habits were not alcohol consumption predictors in
      handball. This study reveal that the typical behaviors regarding alcohol and
      tobacco consumption followed by the general population do not apply to handball
      players. Targeted prevention can be much more precisely established considering
      this research.

PMID- 30279951
TI  - Postural Stability in Goalkeepers of the Polish National Junior Handball Team.
AB  - The aim of the study was to assess postural stability of goalkeepers from the
      Polish national junior handball team. Eleven juniors of the Polish national
      handball team (age 16.82 +/- 1.6 years, body height 191.27 +/- 3.1 cm, body mass
      88.41 +/- 12.26 kg, BMI 24.18 +/- 3.22 kg/m2) were selected for the study. The
      Biodex Balance System and AccuGait AM!TI platform were used to evaluate postural
      stability. The obtained results indicated good postural stability of the
      subjects. During the Biodex Balance System platform tests, all subjects presented
      very good postural stability and maintained within Zone A. Postural sway was
      greater in the sagittal plane compared to the frontal one. Most of the
      participants demonstrated slight backward tilts, but maintained in Quadrant IV.
      During the AccuGait AMTI platform trial, Path Length and Average COP Speed
      significantly increased in the test performed with closed eyes. Furthermore,
      there were significant positive correlations between the number of variables
      obtained during the Biodex Balance System and AccuGait AMTI tests. Proper and
      stable posture are necessary conditions to be met to carry out most free
      movements and locomotion. They play a significant role in the game of a handball
      goalkeeper and for that reason, postural stability testing of handball
      goalkeepers is an important element of coordination training. Thus, the use of
      postural stability exercises implementing the biofeedback method on stabilo and
      dynamometric platforms is practical and justifiable.

PMID- 30279952
TI  - Relation between cutaneous and extracutaneous complications in pediatric patients
      with type 1 diabetes.
AB  - Background: The relationship between cutaneous and extracutaneous complications
      in pediatric patients with type 1 diabetes is unclear. Objective: The objective
      of the current study is to investigate the relationship between skin disorders
      and diabetic microangiopathic changes in pediatric and adolescent patients with
      type 1 diabetes. Patients and methods: Eighty patients with type 1 diabetes and
      50 healthy controls were enrolled in the study. All recruited patients were
      followed up monthly for a total period of 12 month. Monthly visit included
      thorough clinical examination with system review, as well as whole-body cutaneous
      examination. HbA1c was assessed every 3 month. Twenty-four hours urine was
      collected for measurement of urinary albumin. Results: Fifty percent of the
      screened diabetic cohort had diabetic nephropathy (DN). The overall prevalence of
      cutaneous lesion among the studied diabetic cohort was high (72.5%), with
      cutaneous infections (40%) and xerosis (30%) being the most prevalent. The
      frequency of cutaneous infections, xerosis and rubeosis faciei was higher in
      patients with nephropathy than in those without nephropathy. Conclusion:
      cutaneous affection in patients with diabetes may be a clue to the presence of
      associated microangioapthic complications. The significant association between
      diabetic nephropathy and cutaneous lesions support the concept that cutaneous
      lesion in diabetes is a reflection of diabetic angiopathy, highlighting the
      importance of identifying patients at risk of other microvascular complications.

PMID- 30279954
TI  - Drug repurposing using high-throughput screening identifies a promising drug
      combination to treat adrenocortical carcinoma.

PMID- 30279953
TI  - Acanthosis nigricans in the knuckles: An early, accessible, straightforward, and
      sensitive clinical tool to predict insulin resistance.
AB  - Any clinical/biochemical marker revealing obesity or diabetes before their
      appearance is valuable. Insulin resistance (IR) is present in both disorders many
      years before occurrence. Accordingly, we determined whether acanthosis nigricans
      (AN) in the knuckles is associated to higher insulin and homeostasis model
      assessment for estimated insulin resistance (HOMA-IR) index values, and assessed
      the influence of body-mass index (BMI) and the diagnostic performance of AN in
      the knuckles to detect IR. In this cross-sectional controlled study, we included
      men or women, 18 to 23 years old, with or without AN in the knuckles. In 149
      cases with AN in the knuckles and 145 controls, fasting insulin was higher in
      cases (13.45 uU/mL +/- 7.8 vs. 8.59 uU/mL +/- 3.63, P < .001, respectively). Mean
      HOMA-IR index was also higher (2.86 +/- 1.68 vs. 1.78 +/- 0.77, P < .001). A
      significant increase in fasting insulin and HOMA-IR values between and within BMI
      groups from normal through obese category was identified in controls and cases.
      By multivariate regression analysis, cases with normal BMI were significantly
      associated to a HOMA-IR >=2.5 (OR = 3.09, CI95% = 1.75-5.48, P = .001). A model
      of AN in the knuckles, normal BMI, and increased waist circumference allowed
      identifying 2 out of 3 cases with HOMA-IR index >=2.5. AN in the knuckles could
      be addressed with two aims: as an easy, accessible, and costless diagnostic tool
      suggesting hyperinsulinemia secondary to IR, and, an early marker of IR even in
      the absence of overweight or obesity.

PMID- 30279955
TI  - The role of p16 as a biomarker in nonoropharyngeal head and neck cancer.

PMID- 30279956
TI  - Modeling and antitumor studies of a modified L-penetratin peptide targeting E2F
      in lung cancer and prostate cancer.
AB  - E2F1-3a overexpression due to amplification or to mutation or loss of the
      retinoblastoma gene, induces genes involved in DNA synthesis and leads to
      abnormal cellular proliferation, tumor growth, and invasion. Therefore,
      inhibiting the overexpression of one or more of these activating E2Fs is a
      recognized target in cancer therapeutics. In previous studies we identified by
      phage display, a novel 7-mer peptide (PEP) that bound tightly to an immobilized
      consensus E2F1 promoter sequence, and when conjugated to penetratin to increase
      its uptake into cells, was cytotoxic to several malignant cell lines and human
      prostate and small cell lung cancer xenografts. Based on molecular simulation
      studies that showed that the D-Arg penetratin peptide (D-Arg PEP) secondary
      structure is more stable than the L-Arg PEP, the L-Arg in the peptide was
      substituted with D-Arg. In vitro studies confirmed that it was more stable than
      the L- form and was more cytotoxic as compared to the L-Arg PEP when tested
      against the human castrate resistant cell line, DU145 and the human lung cancer
      H196 cell line. When encapsulated in PEGylated liposomes, the D-Arg-PEP potently
      inhibited growth of the DU145 xenograft in mice. Our findings validate D- Arg
      PEP, an inhibitor of E2F1and 3a transcription, as an improved second generation
      drug candidate for targeted molecular therapy of cancers with elevated levels of
      activated E2F(s).

PMID- 30279958
TI  - Glioblastoma in the setting of prior lower grade gliomas - insights from SEER
      database.
AB  - Introduction: Secondary glioblastomas (GBs) constitute a small subset of all GBs
      and tend to arise after a lower grade glioma. Though knowledge regarding this
      subset has gained traction in recent years, its definition continues to evolve,
      complicating its clinical management. Investigation of epidemiology and survival
      patterns may help provide needed insights. Results: The age at GB diagnosis is
      significantly lower (46.22 vs 60.25 years) for group B. The distribution among
      type of GB (glioblastoma, giant cell glioblastoma, or gliosarcoma) was
      significantly different, with no diagnosis of giant cell GB in Group B. Compared
      to Group A, Group B exhibited a higher proportion of females, not married,
      smaller tumors, no GTR, and no radiation (all p < 0.05). GB-related observed
      survivals were comparable. Cox regression with inclusion of co-variates reveal no
      significant influence of GB group on observed survival. Regarding group B, mean
      age was 40.197 for diagnosis of initial lower grade glioma. The most common
      initial ICD-O-3 pathology was oligodendroglioma, NOS; astrocytoma, NOS;
      astrocytoma, anaplastic; and mixed glioma. Methods: The SEER-18 registry was
      queried for patients with GBs. Patients were further classified into two GB
      groups: Group A - those with GB as the only primary tumor, and Group B - those
      with GB as a 2nd primary or subsequent tumor and with history of lower grade
      gliomas. Demographics and clinical factors were compared between group A and B.
      Appropriate statistics were employed to calculate incidences and differences
      among factors and GB-related survivals between the groups. Conclusions: Overall,
      Group B develops GBs at an earlier age, but observed survival remains similar to
      those with GBs as the only primary. Moreover, this subset also exhibit different
      proportions of the types of GBs, and well as differences in other key clinical
      factors (namely, gender and tumor size at presentation). Prior treatments for
      lower grade gliomas likely explain some of the differences noted regarding
      management course after diagnosis of GB.

PMID- 30279957
TI  - Outcome analysis of Phase I trial patients with metastatic KRAS and/or TP53
      mutant non-small cell lung cancer.
AB  - KRAS and TP53 mutations, which are the most common genetic drivers of
      tumorigenesis, are still considered undruggable targets. Therefore, we analyzed
      these genetic aberrations in metastatic non-small cell lung cancer (NSCLC) for
      the development of potential therapeutics. One hundred eighty-five consecutive
      patients with metastatic NSCLC in a phase 1 trial center were included. Their
      genomic aberrations, clinical characteristics, survivals, and phase 1 trial
      therapies were analyzed. About 10%, 18%, 36%, and 36% of the patients had
      metastatic KRAS+/TP53+, KRAS+/TP53-,KRAS-/TP53+, and KRAS-/TP53- NSCLC,
      respectively. The most common concurrent genetic aberrations beside KRAS and/or
      TP53 (>5%) were KIT, epidermal growth factor receptor, PIK3CA, c-MET, BRAF,
      STK11, ATM, CDKN2A, and APC. KRAS+/TP53+ NSCLC did not respond well to the phase
      1 trial therapy and was associated with markedly worse progression-free (PFS) and
      overall (OS) survivals than the other three groups together. KRAS hotspot
      mutations at locations other than codon G12 were associated with considerably
      worse OS than those at this codon. Gene aberration-matched therapy produced
      prolonged PFS and so was anti-angiogenesis in patients with TP53 mutations.
      Introduction of the evolutionary action score system of TP53 missense mutations
      enabled us to identify a subgroup of NSCLC patients with low-risk mutant p53
      proteins having a median OS duration of 64.5 months after initial diagnosis of
      metastasis. These data suggested that patients with metastatic dual KRAS+/TP53+
      hotspot-mutant NSCLC had poor clinical outcomes. Further analysis identified
      remarkably prolonged survival in patients with low-risk mutant p53 proteins,
      which warrants confirmatory studies.

PMID- 30279959
TI  - Metabolite quantification of faecal extracts from colorectal cancer patients and
      healthy controls.
AB  - Colorectal cancer (CRC), a primary cause of morbidity and mortality worldwide is
      expected to rise in the coming years. A better understanding of the metabolic
      changes taking place during the disease progression is needed for effective
      improvements of screening strategies and treatments. In the present study,
      Nuclear Magnetic Resonance (NMR) metabolomics was used to quantify the absolute
      concentrations of metabolites in faecal extracts from two cohorts of CRC patients
      and healthy controls. The quantification of over 80 compounds revealed that
      patients with CRC had increased faecal concentrations of branched chain fatty
      acids (BCFA), isovalerate and isobutyrate plus valerate and phenylacetate but
      diminished concentrations of amino acids, sugars, methanol and bile acids
      (deoxycholate, lithodeoxycholate and cholate). These results suggest that
      alterations in microbial activity and composition could have triggered an
      increase in utilisation of host intestinal slough cells and mucins and led to an
      increase in BCFA, valerate and phenylacetate. Concurrently, a general reduction
      in the microbial metabolic function may have led to reduced levels of other
      components (amino acids, sugars and bile acids) normally produced under healthy
      conditions. This study provides a thorough listing of the most abundant compounds
      found in human faecal waters and presents a template for absolute quantification
      of metabolites. The production of BCFA and phenylacetate in colonic
      carcinogenesis warrants further investigations.

PMID- 30279960
TI  - Single-cell transcriptomes reveal the mechanism for a breast cancer prognostic
      gene panel.
AB  - The clinical benefits of the MammaPrint(r) signature for breast cancer is well
      documented; however, how these genes are related to cell cycle perturbation have
      not been well determined. Our single-cell transcriptome mapping (algorithm)
      provides details into the fine perturbation of all individual genes during a cell
      cycle, providing a view of the cell-cycle-phase specific landscape of any given
      human genes. Specifically, we identified that 38 out of the 70 (54%)
      MammaPrint(r) signature genes are perturbated to a specific phase of the cell
      cycle. The MammaPrint(r) signature panel derived its clinical prognosis power
      from measuring the cell cycle activity of specific breast cancer samples. Such
      cell cycle phase index of the MammaPrint(r) signature suggested that measurement
      of the cell cycle index from tumors could be developed into a prognosis tool for
      various types of cancer beyond breast cancer, potentially improving therapy
      through targeting a specific phase of the cell cycle of cancer cells.

PMID- 30279962
TI  - Role of textural heterogeneity parameters in patient selection for 177Lu-PSMA
      therapy via response prediction.
AB  - Purpose: Prostate cancer is most common tumor in men causing significant patient
      mortality and morbidity. In newer diagnostic/therapeutic agents PSMA linked ones
      are specifically important. Analysis of textural heterogeneity parameters is
      associated with determination of innately aggressive and therapy resistant cell
      lines thus emphasizing their importance in therapy planning. The objective of
      current study was to assess predictive ability of tumor textural heterogeneity
      parameters from baseline 68Ga-PSMA PET prior to 177Lu-PSMA therapy. Results:
      Entropy showed a negative correlation (rs = -0.327, p = 0.006, AUC = 0.695) and
      homogeneity showed a positive correlation (rs = 0.315, p = 0.008, AUC = 0.683)
      with change in pre and post therapy PSA levels. Conclusions: Study showed
      potential for response prediction through baseline PET scan using textural
      features. It suggested that increase in heterogeneity of PSMA expression seems to
      be associated with an increased response to PSMA radionuclide therapy. Materials
      and Methods: Retrospective analysis of 70 patients was performed. All patients
      had metastatic prostate cancer and were planned to undergo 177Lu-PSMA therapy.
      Pre-therapeutic 68Ga- PSMA PET scans were used for analysis. 3D volumes (VOIs) of
      3 lesions each in bones and lymph nodes were manually delineated in static PET
      images. Five PET based textural heterogeneity parameters (COV, entropy,
      homogeneity, contrast, size variation) were determined. Results obtained were
      then compared with clinical parameters including pre and post therapy PSA,
      alkaline phosphate, bone specific alkaline phosphate levels and ECOG criteria.
      Spearman correlation was used to determine statistical dependence among
      variables. ROC analysis was performed to estimate the optimal cutoff value and
      AUC.

PMID- 30279963
TI  - A safety study of newly generated anti-podoplanin-neutralizing antibody in
      cynomolgus monkey (Macaca fascicularis).
AB  - Hematogenous metastases are enhanced by platelet aggregation induced by tumor
      cell-platelet interaction. Podoplanin is a key molecule to enhance the platelet
      aggregation and interacts with C-type lectin-like receptor 2 (CLEC-2) on platelet
      via PLAG domains. Our previous reports have shown that blocking podoplanin
      binding to platelets by neutralizing antibody specific to PLAG4 domain strongly
      reduces hematogenous metastasis. However, podoplanin is expressed in a variety of
      normal tissues such as lymphatic vessels and the question remains whether
      treatment of tumors with anti-podoplanin neutralizing antibodies would be toxic.
      Monkeys are the most suitable species for that purpose. PLAG3 and PLAG4 domains
      had high homology among various monkey species and human. PLAG domain deleted
      mutants were indicated that monkey PLAG4 domain played a more crucial role in
      podoplanin-induced platelet aggregation than did the PLAG3 domain as in human.
      Moreover, newly established neutralizing antibodies (1F6, 2F7, and 3F4) targeting
      the monkey PLAG4 domain blocked interaction between monkey podoplanin and CLEC-2.
      Especially, the 2F7 neutralizing antibody strongly suppressed platelet
      aggregation and pulmonary metastasis. Furthermore, inhibiting podoplanin function
      with 2F7 neutralizing antibody exhibited no acute toxicity in cynomolgus monkeys.
      Our results suggested that targeting podoplanin with specific neutralizing
      antibodies may be an effective anticancer treatment.

PMID- 30279961
TI  - The vesicular transfer of CLIC1 from glioblastoma to microvascular endothelial
      cells requires TRPM7.
AB  - Chloride intracellular channel 1 (CLIC1) is highly expressed and secreted by
      human glioblastoma cells and cell lines such as U87, initiating cell migration
      and tumor growth. Here, we examined whether CLIC1 could be transferred to human
      primary microvascular endothelial cells (HMEC). We previously reported that the
      oncogenic microRNA, miR-5096, increased the release of extracellular vesicles
      (EVs) by which it increased its own transfer from U87 to surrounding cells. Thus,
      we also examined its effect on the CLIC1 transfer. In homotypic cultures, miR
      5096 did not increase the expression of CLIC1 in U87 nor in HMEC. However, the
      endothelial CLIC1 level increased after exposure to EVs released by U87, and even
      more by miR-5096-loaded U87. The EVs-transferred CLIC1 was active in HMEC,
      promoting endothelial sprouting in matrigel. Cell exposure to EVs induced
      cytosolic Ca2+ spikes which were dependent on the transient receptor potential
      melastatin member 7 (TRPM7). TRPM7 silencing prevented Ca2+ spikes and the
      subsequent CLIC1 delivery into HMEC. Our data suggest that the vesicular transfer
      of CLIC1 between cells requires TRMP7 expression in recipient endothelial cells.
      How the vesicular transfer of CLIC1 is modulated in cancer therapy is a future
      challenge.

PMID- 30279964
TI  - Intratumor heterogeneity of HMCN1 mutant alleles associated with poor prognosis
      in patients with breast cancer.
AB  - Human breast cancers comprise a complex and highly heterogeneous population of
      tumor cells. Intratumor heterogeneity is an underlying cause of resistance to
      effective therapies and disease recurrence. To explore prognostic factors based
      on intratumor heterogeneity, we analyzed genomic mutations in breast cancer
      patients registered in The Cancer Genome Atlas. We calculated the variant allele
      frequency (VAF) at each mutation site and evaluated the associations of VAFs with
      the prognosis of breast cancer. VAFs of HMCN1 correlated with the prognosis and
      lymph node status. Although the detailed function of HMCN1 remains unknown, it is
      located in extracellular matrix and the mutation in the gene might be associated
      with cancer cell invasion and metastasis. This finding suggests that HMCN1 is a
      potential metastatic factor and can be a candidate gene for targeted breast
      cancer therapy.

PMID- 30279965
TI  - Assessing the efficacy of androgen receptor and Sox10 as independent markers of
      the triple-negative breast cancer subtype by transcriptome profiling.
AB  - The Androgen Receptor (AR) has recently garnered a lot of attention as a
      potential biomarker and therapeutic target in hormone-dependent cancers,
      including breast cancer. However, several inconsistencies exist within the
      literature as to which subtypes of breast cancer express AR or whether it can be
      used to define its own unique subtype. Here, we analyze 1246 invasive breast
      cancer samples from the Cancer Genome Atlas and show that human breast cancers
      that have been subtyped based on their HER2, ESR1, or PGR expression contain four
      clusters of genes that are differentially expressed across all subtypes. We
      demonstrate that Sox10 is highly expressed in approximately one-third of all
      HER2/ESR1/PGR-low tumors and is a candidate biomarker of the triple-negative
      subtype. Although AR expression is acquired in many breast cancer cases, its
      expression could not define a unique subtype. Despite several reports stating
      that AR expression is acquired in HER2/ESR1/PGR triple-negative cancers, here we
      show that a low percentage of these cancers express AR (~20%). In contrast, AR is
      highly expressed in HER2-positive or ESR1/PGR-positive cancers (> 95%). Although
      AR expression cannot be used as an independent subtype biomarker, our analysis
      shows that routine evaluation of AR expression in tumors which express HER2, ESR1
      and/or PGR may identify a unique subset of tumors which would benefit from anti
      androgen based therapies.

PMID- 30279966
TI  - Loss of Gadd45b accelerates BCR-ABL-driven CML.
AB  - Gadd45b is a member of Gadd45 stress sensor protein family that also includes
      Gadd45a & Gadd45g. To investigate the effect of Gadd45b in bcr-abl oncogene
      driven chronic myeloid leukemia (CML) development, syngeneic wild type lethally
      irradiated mice were reconstituted with either wild type or Gadd45b null myeloid
      progenitors transduced with a retroviral vector expressing BCR-ABL. Loss of
      Gadd45b was observed to accelerate BCR-ABL driven CML development with shortened
      median mouse survival time. BCR-ABL Gadd45b deficient CML progenitors exhibited
      increased proliferation and decreased apoptosis, associated with hyper-activation
      of c-Jun NH2-terminal kinase and Stat5. These results provide novel evidence that
      gadd45b, like gadd45a, functions as a suppressor of BCR-ABL driven leukemia,
      albeit via a different mechanism.

PMID- 30279967
TI  - N-(2'-Hydroxyphenyl)-2-propylpentanamide (OH-VPA), a histone deacetylase
      inhibitor, induces the release of nuclear HMGB1 and modifies ROS levels in HeLa
      cells.
AB  - N-(2'-Hydroxyphenyl)-2-propylpentanamide (OH-VPA) is a valproic acid (VPA)
      derivative with improved antiproliferative activity toward breast cancer (MCF-7,
      MDA-MB-231, and SKBr3) and human cervical cancer cell lines (HeLa) compared to
      that of VPA. However, the pharmacological mechanism of OH-VPA activity remains
      unknown. High-mobility group box 1 (HMGB1) is an important enzyme that is highly
      expressed in tumor cells and has a subcellular localization that is dependent on
      its acetylation or oxidative state. Therefore, in this study, we analyzed changes
      in HMGB1 sub-cellular localization and reactive oxygen species (ROS) as well as
      changes in HeLa cell viability in response to treatment with various
      concentrations of OH-VPA. This compound is formed by the covalent bond coupling
      VPA to a phenol group, which is capable of acting as a free radical scavenger due
      to its chemical similarities to quercetin. Our results show that OH-VPA induces
      nuclear to cytoplasmic translocation of HMGB1, as demonstrated by confocal
      microscopy observations and infrared spectra that revealed high quantities of
      acetylated HMGB1 in HeLa cells. Cells treated with 0.8 mM OH-VA exhibited
      decreased viability and increased ROS levels compared with the lower OH-VPA
      concentrations tested. Therefore, the antiproliferative mechanism of OH-VPA may
      be related to histone deacetylase (HDAC) inhibition, as is the case for VPA,
      which promotes high HMBG1 acetylation, which alters its subcellular localization.
      In addition, OH-VPA generates an imbalance in cellular ROS levels due to its
      biochemical activity.

PMID- 30279969
TI  - Meta-analysis of the likelihood of FOXC2 expression in early- and late-stage
      tumors.
AB  - Background: Aberrations in the expression of the transcription factor forkhead
      box C2 (FOXC2) have been linked to a number of malignancies. Here, we
      characterized the relationship between FOXC2 and cancer progression by conducting
      a meta-analysis of studies that reported the frequency of FOXC2 expression in
      tumors of different stages (T1, T2, T3, T4). Methods: Relevant articles were
      retrieved from the Medline database by searching for the terms "FOXC2" and
      "cancer"; then, the retrieved articles were reviewed individually, and studies
      that were of multivariate cohort design, evaluated FOXC2 expression via
      immunohistochemical staining, and assessed the relationship between FOXC2
      expression and cancer T-stage were included in our meta-analysis. Results: Our
      search terms identified 139 studies, 9 of which met all inclusion criteria. A
      total of 1433 tumor samples were evaluated in the 9 studies; 596 samples were
      from early-stage (T1-T2) tumors, and 838 were from late-stage (T3-T4) tumors.
      FOXC2 was expressed in 46.0% of all samples, in 32.4% of early-stage tumor
      samples, and in 55.6% of late-stage tumor samples. When calculated relative to
      early-stage samples, the pooled risk for FOXC2 expression in late-stage samples
      was 1.367 (95% CI = 1.103-1.695, p = 0.004). Conclusion: The results from our
      meta-analysis of 9 studies indicate that FOXC2 is 36.7% more likely to be
      expressed in late-stage tumors than in early-stage tumors.

PMID- 30279968
TI  - Genetic disruption of calpain-1 and calpain-2 attenuates tumorigenesis in mouse
      models of HER2+ breast cancer and sensitizes cancer cells to doxorubicin and
      lapatinib.
AB  - Calpains are a family of calcium activated cysteine proteases which participate
      in a wide range of cellular functions including migration, invasion, autophagy,
      programmed cell death, and gene expression. Calpain-1 and calpain-2 isoforms are
      ubiquitously expressed heterodimers composed of isoform specific catalytic
      subunits coupled with an obligate common regulatory subunit encoded by capns1.
      Here, we report that conditional deletion of capns1 disrupted calpain-1 and
      calpain-2 expression and activity, and this was associated with delayed
      tumorigenesis and altered signaling in a transgenic mouse model of spontaneous
      HER2+ breast cancer and effectively blocked tumorigenesis in an orthotopic
      engraftment model. Furthermore, capns1 knockout in a tumor derived cell line
      correlated with enhanced sensitivity to the chemotherapeutic doxorubicin and the
      HER2/EGFR tyrosine kinase inhibitor lapatinib. Collectively, these results
      indicate pro-tumorigenic roles for calpains-1/2 in HER2+ breast cancer and
      provide evidence that calpain-1/2 inhibitors could have anti-tumor effects if
      used either alone or in combination with chemotherapeutics and targeted agents.

PMID- 30279972
TI  - Correction: Checkpoint inhibitor induced cardiotoxicity: managing the drawbacks
      of our newest agents against cancer.
AB  - [This corrects the article DOI: 10.18632/oncotarget.22579.].

PMID- 30279970
TI  - Cancer stem cells in progression of colorectal cancer.
AB  - Colorectal cancer is one of the most common cancers worldwide with high
      mortality. Distant metastasis and relapse are major causes of patient death.
      Cancer stem cells (CSCs) play a critical role in the metastasis and relapse of
      colorectal cancer. CSCs are a subpopulation of cancer cells with unique
      properties of self-renewal, infinite division and multi-directional
      differentiation potential. Colorectal CSCs are defined with a group of cell
      surface markers, such as CD44, CD133, CD24, EpCAM, LGR5 and ALDH. They are highly
      tumorigenic, chemoresistant and radioresistant and thus are critical in the
      metastasis and recurrence of colorectal cancer and disease-free survival. This
      review article updates the colorectal CSCs with a focus on their role in tumor
      initiation, progression, drug resistance and tumor relapse.

PMID- 30279973
TI  - Correction: Comparative oncology DNA sequencing of canine T cell lymphoma via
      human hotspot panel.
AB  - [This corrects the article DOI: 10.18632/oncotarget.25209.].

PMID- 30279974
TI  - Silicone breast implant associated fibromatosis.
AB  - Extra-abdominal desmoid tumors, also known as aggressive or deep fibromatosis,
      are uncommon soft tissue tumors that rarely involve the breast. Although the
      exact etiology is unknown, the development of these tumors has been correlated
      with sites of previous trauma, surgery or in association with familial
      adenomatous polyposis. Clinically, breast fibromatosis is often mistaken for
      carcinoma but lacks metastatic potential. It is locally aggressive with high
      rates of recurrence. The treatment is primarily wide local excision with negative
      margins. Adjuvant treatments have been suggested and include radiotherapy,
      chemotherapy and hormonal therapy, however, there are no evidence-based treatment
      protocols to support their use. Here, we describe a case of fibromatosis that
      developed within the capsule around a silicone breast implant treated with
      surgical excision alone. The patient remains recurrence free at 3 months post
      operative magnetic resonance imaging.

PMID- 30279971
TI  - Inhibition of interleukin-1 receptor-associated kinase 1 (IRAK1) as a therapeutic
      strategy.
AB  - Interleukin-1 receptor-associated kinases (IRAK1, IRAK2, IRAK3 [IRAK-M], and
      IRAK4) are serine-threonine kinases involved in toll-like receptor and
      interleukin-1 signaling pathways, through which they regulate innate immunity and
      inflammation. Evidence exists that IRAKs play key roles in the pathophysiologies
      of cancers, and metabolic and inflammatory diseases, and that IRAK inhibition has
      potential therapeutic benefits. Molecules capable of selectively interfering with
      IRAK function and expression have been reported, paving the way for the clinical
      evaluation of IRAK inhibition. Herein, we focus on IRAK1, review its structure
      and physiological roles, and summarize emerging data for IRAK1 inhibitors in
      preclinical and clinical studies.

PMID- 30271579
TI  - WordCommentsAnalyzer: A windows software tool for qualitative research.
AB  - There is a lack of free software that provides a professional and smooth
      experience in text editing and markup for qualitative data analysis. Word
      processing software like Microsoft Word provides a good editing experience,
      allowing the researcher to effortlessly add comments to text portions. However,
      organizing the keywords and categories in the comments can become a more
      difficult task when the amount of data increases. We present
      WordCommentsAnalyzer, a software tool that is written in C# using .NET Framework
      and OpenXml, which helps a qualitative researcher to organize codes when using
      Microsoft Word as the primary text markup software. WordCommentsAnalyzer provides
      an effective user interface to count codes, to organize codes in a code
      hierarchy, and to see various data extracts belonging to each code. It also
      offers basic visualization tools. We illustrate how to use this software by
      conducting a preliminary content analysis on Tweets with the #successfulaging
      hashtag. We also demonstrate that the software has satisfactory performance on a
      large dataset of Iranian journals abstracts. We hope this open-source software
      will facilitate qualitative data analysis by researchers who are interested in
      using Word for this purpose.

PMID- 30271571
TI  - Patent foramen ovale closure versus medical therapy for stroke prevention: A
      systematic review and meta-analysis of randomized controlled trials.
AB  - Background: Previous randomized trials on patent foramen ovale (PFO) closure
      versus medical therapy for stroke prevention were inconclusive. Recently, two new
      randomized trials and new findings from an extended follow-up of a previous trial
      have been published on this topic. We conducted a systematic review and meta
      analysis of randomized trials comparing PFO closure with medical therapy for
      stroke prevention. Methods: PubMed and Cochrane Library were searched until 16 th
      September 2017.  The following search terms were used for PubMed: "patent foramen
      ovale" AND (stroke OR embolism) and "randomized" AND "Trial". For Cochrane
      Library, the following terms were used: "patent foramen ovale" AND "closure" AND
      (stroke OR embolism). Results: A total of 91 and 55 entries were retrieved from
      each database using our search strategy respectively, of which six studies on
      five trials met the inclusion criteria. This meta-analysis included 1829 patients
      in the PFO closure arm (mean age: 45.3 years; 54% male) and 1972 patients in the
      medical therapy arm (mean age: 45.1 years; 51% male). The median follow-up
      duration was 50 +/- 30 months. When compared to medical therapy, PFO closure
      significantly reduced primary endpoint events with a risk ratio [RR] of 0.60 (95%
      CI: 0.44-0.83, P < 0.0001; I 2: 15%). It also reduced stroke (RR: 0.50, 95% CI:
      0.35-0.73, P < 0.0001; I 2: 32%) despite increasing the risk of atrial
      fibrillation/flutter (RR: 1.90, 95% CI: 1.23-2.93, P < 0.01; I 2: 43%). However,
      it did not reduce transient ischemic accident events (0.75; 95% CI: 0.51-1.10, P
      = 0.14; I 2: 0%), all-cause bleeding (RR: 0.89; 95% CI: 0.44-1.78, P = 0.74; I 2:
      51%) or gastrointestinal complications (RR: 0.92; 95% CI: 0.32-2.70, P = 0.88; I
      2: 0%). Conclusions: PFO closure significantly reduces risk of stroke when
      compared to medical treatment and should therefore be considered for stroke
      prevention in PFO patients.

PMID- 30271581
TI  - An opportunity for clinical pharmacology trained physicians to improve patient
      drug safety: A retrospective analysis of adverse drug reactions in teenagers.
AB  - Background: Adverse drug reactions (ADRs) are a major cause of hospital
      admissions, prolonged hospital stays, morbidity, and drug-related mortality. In
      this study, we sought to identify the most frequently reported medications and
      associated side effects in adolescent-aged patients in an effort to prioritize
      clinical pharmacology consultation efforts for hospitals seeking to improve
      patient safety.   Methods: Quarterly reported data were obtained from the United
      States Food and Drug Administration Adverse Events Reporting System (FAERS) from
      the third quarter of 2014 and ending in the third quarter of 2017. We then used
      the GeneCards database to map the pharmacogenomic biomarkers associated with the
      most reported FAERS drugs. Data homogenization and statistics analysis were all
      conducted in R for statistical programming. Results: We identified risperidone
      (10.64%) as the compound with the most reported ADRs from all reported cases.
      Males represented 90.1% of reported risperidone cases with gynecomastia being the
      most reported ADR. Ibuprofen OR=188 (95% CI, 105.00 - 335.00) and quetiapine
      fumarate OR=116 (95% CI, 48.40 - 278.00) were associated with the highest odds of
      completed suicide in teenagers. Ondansetron hydrochloride OR=7.12 (95% CI, 1.59 -
      31.9) resulted in the highest odds of pneumothorax. Lastly, olanzapine (8.96%)
      represented the compound with the most reported drug-drug interactions cases,
      while valproic acid OR=221 (95% CI, 93.900 - 522.00) was associated with the
      highest odds of drug-drug interactions. Conclusion: Despite any data limitations,
      physicians prescribing risperidone in males should be aware of the high rates of
      adverse drug events and an alternative psychotropic should be considered in male
      patients. Further, patients with a history of pneumothorax or genetically
      predisposed to pneumothorax should be considered for an alternative antiemetic to
      ondansetron hydrochloride, due to increased odds associated with the drug and
      adverse event.

PMID- 30271582
TI  - Clinical application of high frequency jet ventilation in stereotactic liver
      ablations - a methodological study.
AB  - Background: Computer-assisted navigation during thermal ablation of liver
      tumours, may help to correct needle placement and improve ablation efficacy in
      percutaneous, laparoscopic and open interventions. The potential advantage of
      using high frequency jet-ventilation technique (HFJV) during the procedure is by
      minimising the amplitude of respiration-related upper-abdominal organs movements.
      The aim of this clinical methodological trial was to establish whether HFJV would
      give less ventilatory induced liver movements than conventional ventilation,
      during stereotactic navigated ablation of liver metastases under open surgery.
      Methods: Five consecutive patients scheduled for elective, open liver ablation
      under general propofol and remifentanil anaesthesia were included in the study
      protocol. During the stereotactic targeting of the tumours, HFJV was chosen for
      intraoperative lung ventilation. For tracking of liver movement, a rigid marker
      shield was placed on the liver surface and tracked with an optical position
      measurement system. A 4D position of the marker shield was measured for HFJV and
      conventional tidal volume lung ventilation (TV). At each time point the magnitude
      of liver displacement was calculated as an Euclidean distance between
      translational component of the marker shield's 3D position and previously
      estimated centroid of the translational motion. Results: The mean Euclidean liver
      displacement was 0.80 (0.10) mm for HFJV and 2,90 (1.03) mm for TV with maximum
      displacement going as far as 12 mm on standard ventilation (p=0.0001).
      Conclusion: HFJV is a valuable lung ventilation method for patients undergoing
      stereotactic surgical procedures in general anaesthesia when reduction of organ
      displacement is crucial.

PMID- 30279980
TI  - Computer assisted system for precise lung surgery based on medical image
      computing and mixed reality.
AB  - The key of a surgical treatment for the lung cancer is to remove the infected
      part with the least excision and to retain most of the healthy lung tissue. The
      traditional computer surgery assisted system show that the patient's CT images or
      three-dimensional structure in the PC screen. This assisted system is not a real
      three-dimensional system and can't display well the position of pulmonary vessels
      and trachea of the patients to surgeon. To solve the problem, a computer assisted
      system for precise lung surgery for precise surgery based on medical image and VR
      is developed in this paper. Firstly, the regional growth and filling algorithm is
      designed to segment lung trachea and lung vessels. Then, the reference edge grid
      algorithm is used to construct the model of the segmentation trachea and lung
      vessels. And the models are saved as an identifiable STL type file. Finally,
      according to the system analysis for the specific system function, the computer
      assisted system is implemented to display the three-dimensional pulmonary vessels
      and trachea on the mixed reality device. The surgeons can observe and interface
      precisely the real three-dimensional lung structure of the patient to help them
      operate accurately the lung surgery.

PMID- 30271584
TI  - A systematic performance evaluation of clustering methods for single-cell RNA-seq
      data.
AB  - Subpopulation identification, usually via some form of unsupervised clustering,
      is a fundamental step in the analysis of many single-cell RNA-seq data sets. This
      has motivated the development and application of a broad range of clustering
      methods, based on various underlying algorithms. Here, we provide a systematic
      and extensible performance evaluation of 14 clustering algorithms implemented in
      R, including both methods developed explicitly for scRNA-seq data and more
      general-purpose methods. The methods were evaluated using nine publicly available
      scRNA-seq data sets as well as three simulations with varying degree of cluster
      separability. The same feature selection approaches were used for all methods,
      allowing us to focus on the investigation of the performance of the clustering
      algorithms themselves. We evaluated the ability of recovering known
      subpopulations, the stability and the run time and scalability of the methods.
      Additionally, we investigated whether the performance could be improved by
      generating consensus partitions from multiple individual clustering methods. We
      found substantial differences in the performance, run time and stability between
      the methods, with SC3 and Seurat showing the most favorable results.
      Additionally, we found that consensus clustering typically did not improve the
      performance compared to the best of the combined methods, but that several of the
      top-performing methods already perform some type of consensus clustering. All the
      code used for the evaluation is available on GitHub (
      https://github.com/markrobinsonuzh/scRNAseq_clustering_comparison). In addition,
      an R package providing access to data and clustering results, thereby
      facilitating inclusion of new methods and data sets, is available from
      Bioconductor ( https://bioconductor.org/packages/DuoClustering2018).

PMID- 30279981
TI  - Optimizing spatial healthcare assets with Internet of Things.
AB  - Six percent of the total cost of healthcare delivery in Australia is from buying,
      building and maintaining physical assets. Current practice does not measure the
      efficient use of existing clinical spaces prior to making funding decisions for
      service expansion, remodeling or relocation. Healthcare service delivery can be
      increased through existing assets by optimizing the use of clinical space. The
      wait times for healthcare service consumers and capital expenditure pressures
      could be reduced, which would result in increased funds available for frontline
      services. Sensor technology has been used to study aspects of time in ambulatory
      outpatient clinics using Infra-red Tags or Radio Frequency Identification tags.
      This paper proposes the use of Internet of Things (IoT) technology to assist in
      the optimization of high-value clinical spaces and presents phase one of the
      project where a trial was held in a non-clinical location to evaluate sensor
      performance. In Phase two, sensors will be installed to count people across an
      ambulatory outpatient clinic in a live public healthcare environment to
      understand clinical space utilization and inform decision-makers. The data
      produced by the sensors on room use is processed for visualization in "dashboard"
      format so frontline and executive staff have evidence-based decision-making
      support for space optimization strategies. This paper presents the phase one
      trial and preliminary results that show the disparity space utilization patterns
      between the IoT sensed occupancy data with the current room reservation system in
      a non-clinical space.

PMID- 30279982
TI  - Emotion classification using flexible analytic wavelet transform for
      electroencephalogram signals.
AB  - Emotion based brain computer system finds applications for impaired people to
      communicate with surroundings. In this paper, electroencephalogram (EEG) database
      of four emotions (happy, fear, sad, and relax) is recorded and flexible analytic
      wavelet transform (FAWT) is proposed for the emotion classification. FAWT
      analyzes the EEG signal into sub-bands and statistical measures are computed from
      the sub-bands for extraction of emotion specific information. The emotion
      classification performance of sub-band wise extracted features is examined over
      the variants of k-nearest-neighbor (KNN) classifier. The weighted-KNN provides
      the best emotion classification performance 86.1% as compared to other KNN
      variants. The proposed method shows better emotion classification performance as
      compared to other existing four emotions classification methods.

PMID- 30279983
TI  - Features based on variational mode decomposition for identification of
      neuromuscular disorder using EMG signals.
AB  - Neuromuscular disorder is a muscular and nervous disorder resulting in muscular
      weakness and progressively damages nervous control, such as amyotrophic lateral
      sclerosis (ALS) and myopathy (MYO). Its diagnosis can be possible by
      classification of ALS, MYO, and normal electromyogram (EMG) signals. In this
      paper, an effective method based on variational mode decomposition (VMD) is
      proposed for identification of neuromuscular disorder of EMG signals. VMD is an
      adaptive signal decomposition which decomposes EMG signals nonrecursively into
      band-limited functions or modes. These modes are used for extraction of spectral
      features, particularly spectral flatness, spectral spread, spectral decrease and
      statistical features like kurtosis, mean absolute deviation, and interquartile
      range. The extracted features are fed to the extreme learning machine classifier
      in order to classify neuromuscular disorder of EMG signals. The performance of
      obtained results shows that the method used provides a better classification for
      neuromuscular disorder of EMG signals as compared to existing methods.

PMID- 30279985
TI  - Survey of energy drink consumption and adverse health effects in Lebanon.
AB  - Consumption of energy is a national and international phenomenon that showed
      increase in market spread and profits from 1990 and made the emergence of many
      brands. Energy drinks are aggressively marketed with the claim that these
      products give an energy boost to improve physical and cognitive performance.
      However, studies supporting these claims are limited. The study examines the new
      phenomena of energy drinks among university students in Lebanon, based on the
      participants' personnel characteristics, university grade and the impact on
      health status. The study also determined whether high frequency of consumption
      was correlated with negative physical health symptoms. A cross-sectional study
      survey was undertaken on students aged between 18 and 30 years in private
      university over three branches (Beirut, Tripoli and Saida). A self-administered
      questionnaire was used inquiring about socio-demographic characteristics,
      consumption patterns and side effect of energy drinks. Data was analyzed using
      SPSS 24. Findings showed a serious concern exists for the health and safety of
      the most at risk students who engaged in daily energy drink usage when two-thirds
      of these reported difficulties sleeping, more than one experienced heart
      palpitation and blood pressure; one-third had anxiety, nervousness and feeling
      thirsty, and one fifth indicated tiredness and headache. Such symptoms are
      reported with excessive consumption of caffeine that had adverse health effect on
      the body.

PMID- 30279984
TI  - A study on medical Internet of Things and Big Data in personalized healthcare
      system.
AB  - Personalized healthcare systems deliver e-health services to fulfill the medical
      and assistive needs of the aging population. Internet of Things (IoT) is a
      significant advancement in the Big Data era, which supports many real-time
      engineering applications through enhanced services. Analytics over data streams
      from IoT has become a source of user data for the healthcare systems to discover
      new information, predict early detection, and makes decision over the critical
      situation for the improvement of the quality of life. In this paper, we have made
      a detailed study on the recent emerging technologies in the personalized
      healthcare systems with the focus towards cloud computing, fog computing, Big
      Data analytics, IoT and mobile based applications. We have analyzed the
      challenges in designing a better healthcare system to make early detection and
      diagnosis of diseases and discussed the possible solutions while providing e
      health services in secure manner. This paper poses a light on the rapidly growing
      needs of the better healthcare systems in real-time and provides possible future
      work guidelines.

PMID- 30279987
TI  - Evolution of blood pressure control identification in lieu of post-surgery
      diabetic patients: a review.
AB  - The blood pressure disparity is the major problem in post-operative surgery
      especially diabetic patients, because there is substantial interrelation between
      diabetic and hypertension and this abnormality creates complicated problems and
      needs to be controlled by continuous monitoring based on the severity. To
      overcome this problem, implementation of automatic drug infusion is required for
      critical patients, by which workload of the clinical staffs are reduced. Most
      commonly the sodium nitroprusside (SNP) is used to reduce the blood pressure in
      fast action based on the prescribed level. In this paper three different types of
      estimation techniques (PID, IMC and MPC) are uses to identify the valuation. The
      strength of the projected controller performance is evaluated under different
      types of patients such as sensitive, and normal along with insensitive patients.
      Therefore, this paper review the validation results based on the optimized SNP
      infusion rate for persistent Blood pressure control compare then the reviewed
      methods. The MATLAB simulation is used to evaluate the efficiency of the proposed
      work and obtain the results based on the projected values.

PMID- 30279986
TI  - Cloud based framework for diagnosis of diabetes mellitus using K-means
      clustering.
AB  - Diabetes mellitus is a serious health problem affecting the entire population all
      over the world for many decades. It is a group of metabolic disorder
      characterized by chronic disease which occurs due to high blood sugar, unhealthy
      foods, lack of physical activity and also hereditary. The sorts of diabetes
      mellitus are type1, type2 and gestational diabetes. The type1 appears during
      childhood and type2 diabetes develop at any age, mostly affects older than 40.
      The gestational diabetes occurs for pregnant women. According to the statistical
      report of WHO 79% of deaths occurred in people under the age of 60, due to
      diabetes. With a specific end goal to deal with the vast volume, speed,
      assortment, veracity and estimation of information a scalable environment is
      needed. Cloud computing is an interesting computing model suitable for
      accommodating huge volume of dynamic data. To overcome the data handling problems
      this work focused on Hadoop framework along with clustering technique. This work
      also predicts the occurrence of diabetes under various circumstances which is
      more useful for the human. This paper also compares the efficiency of two
      different clustering techniques suitable for the environment. The predicted
      result is used to diagnose which age group and gender are mostly affected by
      diabetes. Further some of the attributes such as hyper tension and work nature
      are also taken into consideration for analysis.

PMID- 30279988
TI  - Transfer learning based histopathologic image classification for breast cancer
      detection.
AB  - Breast cancer is one of the leading cancer type among women in worldwide. Many
      breast cancer patients die every year due to the late diagnosis and treatment.
      Thus, in recent years, early breast cancer detection systems based on patient's
      imagery are in demand. Deep learning attracts many researchers recently and many
      computer vision applications have come out in various environments. Convolutional
      neural network (CNN) which is known as deep learning architecture, has achieved
      impressive results in many applications. CNNs generally suffer from tuning a huge
      number of parameters which bring a great amount of complexity to the system. In
      addition, the initialization of the weights of the CNN is another handicap that
      needs to be handle carefully. In this paper, transfer learning and deep feature
      extraction methods are used which adapt a pre-trained CNN model to the problem at
      hand. AlexNet and Vgg16 models are considered in the presented work for feature
      extraction and AlexNet is used for further fine-tuning. The obtained features are
      then classified by support vector machines (SVM). Extensive experiments on a
      publicly available histopathologic breast cancer dataset are carried out and the
      accuracy scores are calculated for performance evaluation. The evaluation results
      show that the transfer learning produced better result than deep feature
      extraction and SVM classification.

PMID- 30279989
TI  - Clinical factors affecting perioperative outcomes in robot-assisted radical
      prostatectomy.
AB  - The present study investigated clinical factors affecting perioperative outcomes
      in robot-assisted radical prostatectomy (RARP). The study included 625 Japanese
      cases treated with RARP between 2009 and 2017. The association between clinical
      factors (age, overweight status, prostate volume, clinical T-stage, nerve
      sparing, lympho-node dissection, and the number of experienced cases) and
      perioperative outcomes (operation time, estimated blood loss, catheterization
      duration, and perioperative complication) were analyzed. Results revealed that
      overweight status, prostate volume, lymph-node dissection, and the number of
      experienced cases were associated with operation time. For estimated blood loss,
      the identified risk factors were overweight status, prostate volume, nerve
      sparing, lymph-node dissection, and the number of experienced cases. Lymph-node
      dissection and the number of experienced cases were also associated with
      catheterization duration. Additionally, only lymph-node dissection was associated
      with increased perioperative complication. Taken together, the present study
      identified several clinical factors affecting perioperative outcomes in RARP.
      This information may help surgeons to estimate perioperative outcomes as well as
      to inform patients.

PMID- 30279990
TI  - Suppression of LOX activity enhanced seed vigour and longevity of tobacco
      (Nicotiana tabacum L.) seeds during storage.
AB  - The preservation of seed viability and quality in storage is an important trait
      both for commercial and germplasm usage. To better explore potential mechanisms
      of tobacco seed deterioration, seed packed in cloth bag (C) and vacuum bag (V)
      were stored under room temperature (RT) and low temperature (LT, 18 degrees C),
      and sampled periodically for laboratory testing. Seed stored in low temperature
      with vacuum bag (LT/V) owned the highest seed vigour after 25 months of storage
      and in room temperature with cloth bag (RT/C) lost seed vigour and germination
      ability after 20-month storage. Meanwhile, seed in RT/C notably increased about 5
      fold endogenous hydrogen peroxide (H2O2), 4-fold malondialdehyde (MDA) contents,
      12-fold Lipoxygenases (LOX) activity and 2-fold the expression of NtLOX3
      comparing with LT/V at the end of 15-month storage. In addition, regression
      analysis indicated that LOX activity was strongly negatively correlated with seed
      vigour as the R 2 value reached 0.970 in RT/C. Furthermore, caffeic acid and
      catechin, the inhibitors of LOX activity, were applied to tobacco seeds pre
      treatment and followed with artificial accelerated aging. Seeds pretreated with
      inhibitors, especially caffeic acid, reduced LOX activity by 50%, MDA and H2O2
      contents by 40% and 20%, respectively, and increased more than 1.2-fold seed
      vigour and seedling quality comparing with seeds pretreated with H2O after 6-day
      artificial aging, indicating a better seed storability after artificial
      accelerated aging. These results suggest that LOX accelerated seed aging, and
      suppression of LOX activity enhanced seed vigour and viability in accelerated
      aging tobacco seed, opening new opportunities for effective management of seed
      germplasm under long-term storage and conservation.

PMID- 30279991
TI  - Integrating physiological stress into the movement ecology of migratory
      ungulates: a spatial analysis with mule deer.
AB  - Rapid climate and human land-use change may limit the ability of long-distance
      migratory herbivores to optimally track or 'surf' high-quality forage during
      spring green-up. Understanding how anthropogenic and environmental stressors
      influence migratory movements is of critical importance because of their
      potential to cause a mismatch between the timing of animal movements and the
      emergence of high-quality forage. We measured stress hormones (fecal
      glucocorticoid metabolites; FGMs) to test hypotheses about the effects of high
      quality forage tracking, human land-use and use of stopover sites on the
      physiological state of individuals along a migratory route. We collected and
      analysed FGM concentrations from 399 mule deer (Odocoileus hemionus) samples
      obtained along a 241-km migratory route in western Wyoming, USA, during spring
      2015 and 2016. In support of a fitness benefit hypothesis, individuals occupying
      areas closer to peak forage quality had decreased FGM levels. Specifically, for
      every 10-day interval closer to peak forage quality, we observed a 7% decrease in
      FGMs. Additionally, we observed support for both an additive anthropogenic stress
      hypothesis and a hypothesis that stopovers act as physiological refugia, wherein
      individuals sampled far from stopover sites exhibited 341% higher FGM levels if
      in areas of low landscape integrity compared to areas of high landscape
      integrity. Overall, our findings indicate that the physiological state of mule
      deer during migration is influenced by both anthropogenic disturbances and their
      ability to track high-quality forage. The availability of stopovers, however,
      modulates physiological responses to those stressors. Thus, our results support a
      recent call for the prioritization of stopover locations and connectivity between
      those locations in conservation planning for migratory large herbivores.

PMID- 30279992
TI  - Assay validation and interspecific comparison of salivary glucocorticoids in
      three amphibian species.
AB  - Amphibians are one of the most threatened groups of species, facing stressors
      ranging from habitat degradation and pollution to disease and overexploitation.
      Stress hormones (glucocorticoids, GCs) provide one quantitative metric of stress,
      and developing non-invasive methods for measuring GCs in amphibians would clarify
      how diverse environmental stressors impact individual health in this taxonomic
      group. Saliva is an advantageous matrix for quantifying GCs, as it is sampled
      less invasively than plasma while still detecting both baseline and acute
      elevation of GCs within a short timeframe. Little work has employed this method
      in amphibian species, and it has never been pharmacologically and biologically
      validated. Here, we conduct analytical, pharmacological and biological validation
      experiments for measuring salivary corticosterone in three amphibian species: the
      American bullfrog (Rana catesbeiana), the green frog (Rana clamitans) and the
      northern leopard frog (Rana pipiens). These species are faced with a broad range
      of environmental challenges, and in part of its range R. pipiens populations are
      currently in decline. In addition to demonstrating that this method can be
      reliably used in multiple amphibian species, we present an examination of
      intrinsic biological factors (sex, body condition) that may contribute to GC
      secretion, and a demonstration that saliva can be collected from free-living
      animals in the field to quantify corticosterone. Our findings suggest that saliva
      may be useful for less invasively quantifying GCs in many amphibian species.

PMID- 30279993
TI  - Lipoma in dogs under primary veterinary care in the UK: prevalence and breed
      associations.
AB  - Background: Lipomas are masses of mesenchymal origin, comprising of adipocytes,
      and are often clinically unremarkable but can be alarming to owners. Although
      lipomas are reportedly common in dogs, no studies have specifically investigated
      risk factors associated with their occurrence. This study was a large-scale
      retrospective analysis of electronic patient records of dogs attending practices
      participating in VetCompassTM. Univariable and multivariable logistic regression
      methods were used to evaluate associations between risk factors and primary-care
      veterinary diagnosis of lipoma. Results: From 384,284 dogs under veterinary care
      during 2013 at 215 primary practice clinics in the UK, there were 2765 lipoma
      cases identified giving a one-year prevalence of 1.94% (95% CI: 1.87-2.01).
      Breeds with the highest lipoma prevalence included Weimaraner (7.84%, 95% CI 6.46
      9.40), Dobermann Pinscher (6.96%, 95% CI 5.67-8.44), German Pointer (5.23%, 95%
      CI 3.93-6.80), Springer Spaniel (5.19%, 95% CI 4.76-5.66), and Labrador Retriever
      (5.15%, 95% CI 4.90-5.41). Dogs with an adult bodyweight equal or higher than
      their breed/sex mean had 1.96 (95% CI 1.81-2.14, P <  0.001) times the odds of
      lipoma compared with dogs that weighed below their breed/sex mean. The odds of
      lipoma increased as adult bodyweight increased. Increased age was strongly
      associated with increasing odds of lipoma. Compared with dogs aged 3.0 to < 6.0
      years, dogs aged 9.0 - < 12.0 years had 17.52 times the odds (95% CI 14.71-20.85,
      P <  0.001) of lipoma. Neutered males (OR: 1.99, 95% CI 1.69-2.36, P <  0.001)
      and neutered females (OR: 1.62, 95% CI 1.37-1.91, P <  0.001) had higher odds
      than entire females. Insured dogs had 1.78 (95% CI 1.53-2.07, P <  0.001) times
      the odds of lipoma compared with uninsured dogs. Conclusions: Lipomas appear to
      be a relatively common diagnosis in primary-care practice. Certain breeds were
      identified with remarkably high lipoma prevalence, highlighting the risk that
      owners should be prepared for. Lipoma predisposition of larger bodyweight
      individuals within breed/sex suggests that being overweight or obese may be a
      predisposing factor but would need further work to confirm.

PMID- 30279994
TI  - Diagnosis and management of a heterotopic pregnancy and ruptured rudimentary
      uterine horn.
AB  - Background: Heterotopic pregnancies implanted in a rudimentary uterine horn
      account for 1 in 2-3 million gestations, and confer significant risk of morbidity
      due to uterine rupture and hemorrhage. Case presentation: A 34-year-old nullipara
      presented with acute pelvic pain at 17 weeks of gestation with dichorionic
      diamniotic twins, one in each horn of an anomalous uterus first diagnosed in
      pregnancy as bicornuate. Three-dimensional ultrasound and MRI revealed myometrial
      disruption in the left rudimentary uterine horn, and the patient underwent an
      uncomplicated abdominal hemi-hysterectomy. Fourteen days later, an uncomplicated
      dilation and curettage was performed for a fetal anomaly in the remaining twin in
      the right unicornuate uterus. Conclusion: This case demonstrates the utility of
      magnetic resonance imaging and three-dimensional ultrasound in the assessment of
      myometrial integrity in a gravid patient with a heterotopic pregnancy and
      ruptured rudimentary uterine horn. This case demonstrates the importance of pre
      pregnancy diagnosis and management of mullerian anomalies.

PMID- 30279995
TI  - Flexible Bronchoscopy Under Bronchoscopist-Administered Moderate Sedation Versus
      General Anesthesia: A Comparative Study in Children.
AB  - Background: Flexible bronchoscopy (FB) can be performed under bronchoscopist
      administered moderate sedation (BAMS) with a midazolam/fentanyl combination or
      general anesthesia (GA). However, the outcome of BAMS has not been well
      established in children. Currently, most of the centers prefer FB under GA. Both
      techniques have their advantages and disadvantages with implications for safety,
      complications, and diagnostic yield. The primary objective of our study was to
      evaluate the safety, time efficiency, and cost-effectiveness of FB under BAMS as
      compared with FB under GA in a similar setting. Methods: We performed a
      retrospective chart review to compare BAMS versus GA for FB in children. We
      recruited BAMS children (n = 295) from University of Florida (UF) Health Shands
      Children's Hospital, and GA children (n = 100) from Penn State Children's
      Hospital (PSHCH). Both the groups had similar indications, complexities, and
      procedural environments. Comparisons of various time-intervals including
      preprocedure time, sedation-induction time, scope time, and post-procedure time
      among different BAMS versus GA age-groups were the primary outcomes. The
      secondary outcomes were the determination of the rates of complications, the
      dosages of sedative/anesthetic, cost-effectiveness, and sedation patterns under
      BAMS. Results: FB under BAMS required significantly higher preprocedure times and
      sedation-induction times (P < 0.001** and P < 0.001** respectively) but shorter
      scope and post-procedure times compared with the GA group times (P < 0.001** and
      P < 0.001** respectively). Younger children had a deeper level of sedation for an
      extended period under BAMS. The costs for the sedation services and the
      complication rates were lower in the BAMS group compared with the GA group.
      Conclusion: Our study demonstrated the feasibility of BAMS in children. FB under
      BAMS had an advantage of lower cost and fewer procedural complications compared
      with FB under GA. Despite that, the safety of BAMS could not be conclusively
      established from this retrospective study. Moreover, BAMS can potentially
      compromise the diagnostic yield because the bronchoscopist is also responsible
      for monitoring sedation and managing the airway.

PMID- 30279996
TI  - Recent Trends in Unpasteurized Fluid Milk Outbreaks, Legalization, and
      Consumption in the United States.
AB  - INTRODUCTION: Determining the potential risk of foodborne illness has become
      critical for informing policy decisions, due to the increasing availability and
      popularity of unpasteurized (raw) milk. METHODS: Trends in foodborne illnesses
      reported to the Centers for Disease Control in the United States from 2005 to
      2016 were analyzed, with comparison to state legal status and to consumption, as
      estimated by licensing records. RESULTS: The rate of unpasteurized milk
      associated outbreaks has been declining since 2010, despite increasing legal
      distribution. Controlling for growth in population and consumption, the outbreak
      rate has effectively decreased by 74% since 2005. DISCUSSION: Studies of the role
      of on-farm food safety programs to promote the further reduction of unpasteurized
      milk outbreaks should be initiated, to investigate the efficacy of such risk
      management tools.

PMID- 30279997
TI  - Removal of the Mitochondrial Fission Factor Mff Exacerbates Neuronal Loss and
      Neurological Phenotypes in a Huntington's Disease Mouse Model.
AB  - OBJECTIVE: Excessive mitochondrial fission has been associated with several
      neurodegenerative diseases, including Huntington's disease (HD). Consequently,
      mitochondrial dynamics has been suggested to be a promising therapeutic target
      for Huntington's disease. Mitochondrial fission depends on recruitment of Drp1 to
      mitochondria, and Mff (mitochondrial fission factor) is one of the key adaptor
      proteins for this process. Removal of Mff therefore greatly reduces mitochondrial
      fission. Here we investigate whether removal of Mff can mitigate HD-associated
      pathologies in HD transgenic mice (R6/2) expressing mutant Htt. METHOD: We
      compared the phenotype of HD mice with and without Mff. The mice were monitored
      for lifespan, neurological phenotypes, Htt aggregate formation, and brain
      histology. RESULTS: We found that HD mice lacking Mff display more severe
      neurological phenotypes and have shortened lifespans. Loss of Mff does not affect
      mutant Htt aggregation, but it accelerates HD pathology, including neuronal loss
      and neuroinflammation. CONCLUSIONS: Our data indicate a protective role for
      mitochondrial fission in HD and suggest that more studies are needed before
      manipulation of mitochondrial dynamics can be applied to HD therapy.

PMID- 30279998
TI  - Comparison of Green Versus Blue Fundus Autofluorescence in ABCA4-Related
      Retinopathy.
AB  - Purpose: To investigate the interreader and intermodality agreement for grading
      of retinal pigment epithelium (RPE) atrophy lesion size in ABCA4-related
      retinopathy using green (GAF) and blue fundus autofluorescence (BAF) imaging.
      Methods: In this cross-sectional case series, 97 eyes of 49 patients with RPE
      atrophy secondary to ABCA4-related retinopathy underwent GAF- (518 nm excitation
      light) and BAF- (488 nm excitation light) imaging using confocal scanning laser
      ophthalmoscopy (Spectralis HRA, Heidelberg Engineering, Heidelberg, Germany).
      Lesions with definitely decreased autofluorescence (DDAF) and questionably
      decreased autofluorescence (QDAF) in GAF and BAF imaging were analyzed separately
      by five independent readers using semiautomated software (RegionFinder,
      Heidelberg Engineering). Intermodality and interreader agreements were assessed
      for the square-root lesion size, lesion perimeter, and circularity. Results: GAF-
      and BAF-based measurements of DDAF and QDAF showed high intermodality and
      interreader agreement concerning square-root lesion size, as well as shape
      descriptive parameters (perimeter and circularity). Interreader agreement of
      square-root lesion size was slightly, hence not significantly higher for GAF
      based grading ([95% coefficients of repeatability, intraclass correlation
      coefficient] DDAF: 0.215 mm, 0.997; QDAF: 0.712 mm, 0.981) compared to BAF-based
      grading (DDAF: 0.232 mm, 0.997; QDAF: 0.764 mm, 0.978). However, DDAF
      measurements revealed distinctly more reproducible results than QDAF
      measurements. Foveal sparing did not interfere with intermodality agreement.
      Conclusions: Both GAF- and BAF-based quantification of RPE atrophy showed very
      reliable results with possible superiority of GAF in the context of less
      energetic excitation light. Translational Relevance: The high interreader
      agreement qualifies the use of DDAF progression in GAF and BAF imaging as
      potential morphologic outcome measure for interventional clinical trials and
      disease monitoring.

PMID- 30279999
TI  - Development and Validation of the Singapore Thyroid Eye Disease Quality of Life
      Questionnaire.
AB  - Purpose: Current instruments to assess thyroid eye disease (TED) quality of life
      (QoL) were not developed using modern psychometric theory and may not be
      applicable to Asian populations. Therefore, we developed a psychometrically
      robust questionnaire, the Singapore Thyroid Eye Disease Quality of Life
      questionnaire (STED-QoL), for assessing QoL in Asian patients. Methods: This
      cross-sectional study was conducted at the Singapore National Eye Centre between
      2012 and 2015. In Phase 1, content for the questionnaire was developed using
      qualitative methods. A total of 20 patients participated in three different focus
      groups. Thematic analysis was conducted to identify relevant themes from which 12
      items, rated on a 5-point Likert-type scale, were generated. In Phase 2, the
      pilot instrument was administered to 59 TED patients and psychometric assessment
      of the STED-QoL was conducted using Rasch analysis. Results: After collapsing
      categories from five to four and deleting two misfitting items, we generated a 10
      item STED-QoL befitting the Rasch model. The scale showed good criterion
      validity, with scores decreasing as severity of TED worsened: mild (1.78 logits),
      moderate (0.27 logits), and severe (0.92 logits). A 'Psychosocial' subscale also
      had adequate psychometric properties and psychosocial scores were significantly
      worse in those who underwent surgery for TED compared to those who had not (0.41
      vs. 1.82 logits, P = 0.021). Conclusions: The STED-QoL is a robust 10-item
      questionnaire specifically developed to measure the impact of TED on QoL and
      psychosocial well-being in an Asian population. Translational Relevance: QoL
      assessment is important for holistic management of TED patients.

PMID- 30280000
TI  - Functional Staging of Corneal Neovascularization Using Fluorescein and
      Indocyanine Green Angiography.
AB  - Purpose: Corneal neovascularization (CoNV) is a major risk factor for corneal
      graft rejection and other corneal conditions. The maturity of CoNV is important
      to guide treatment. This study investigated associations between clinical and
      angiographic characteristics of CoNV. Methods: In a prospective cross-sectional
      study patients with CoNV of variable but known duration and etiology were
      included. All cases were clinically staged according to a simplified three-grade
      scale as active, inactive, and regressed and assessed using color photography,
      anterior-segment optical coherence tomography, and fluorescein and indocyanine
      green (ICG) angiography. Outcome parameters included age and depth of CoNV,
      perfusion times and time to leakage of fluorescein and ICG. Results: Forty eyes
      of 39 patients with CoNV were included, active (14), inactive (22), and regressed
      CoNV (4). There were significant associations between the time to fluorescein or
      ICG leakage and clinical staging of CoNV (R 2 = 0.24; P = 0.0011, and R 2 = 0.3;
      P = 0.0001). In addition, there was a significant association between the time to
      fluorescein leakage and the age of CoNV (R 2 = 0.32; P = 0.0002). ICG leakage
      within 10 minutes was observed significantly more frequently in active than the
      inactive group and was not observed in regressed cases (P < 0.0001). Conclusions:
      Simplification of the staging of CoNV to active, inactive, and regressed to is
      significantly associated with the time to extravascular leakage of fluorescein
      and indocyanine and may be useful to guide the selection of appropriate
      treatments. Translational Relevance: The association between clinical and
      angiographic characteristics of CoNV may provide guidance to the treatment
      approaches.

PMID- 30280001
TI  - Measurable Range of Subfoveal Choroidal Thickness With Conventional Spectral
      Domain Optical Coherence Tomography.
AB  - Purpose: We investigate the measurable range of subfoveal choroidal thickness
      (SFCT) with conventional spectral domain optical coherence tomography (SD-OCT) in
      normal healthy eyes. Methods: All subjects underwent an SD-OCT horizontal line
      scan centered at the fovea with standard and enhanced depth imaging (EDI)
      techniques. Two independent observers manually measured SFCT on standard and EDI
      OCT images, if two choroidal borders were identified. The rate of successful
      measurement with standard OCT was evaluated. Inter- and intraclass correlation
      coefficients and Bland-Altman plots were used for analysis. Results: OCT images
      of 724 normal healthy eyes from 374 subjects were evaluated. Although the inner
      choroidal border was identified on all OCT images, the outer choroidal border was
      identified on 378 of 724 (52.2%) conventional OCT images. Mean SFCT of all study
      eyes measured by EDI-OCT images was 292.6 +/- 94.0. The number of successful
      measurements with conventional OCT was 100%, 87.5%, 48.1%, 33.0%, and 0%, in the
      SFCT ranges of <241, 241-280, 281-320, 321-360, and >360 MUm, respectively. The
      accumulated rate of successful measurement with conventional OCT was 100%, 96.4%,
      and 82.2% in the SFCT ranges of <=240, <=280, and <=320 MUm, respectively. Two
      protocols showed good inter-correlation of SFCT, when SFCT were measurable in
      both scans. Conclusions: SFCT can be measured by conventional OCT in eyes with
      thin choroid, and the measured value shows high agreement with those measured by
      EDI-OCT. In such eyes, conventional OCT can be used potentially to evaluate the
      retina and choroid. Translational Relevance: In eyes with a thin choroid,
      conventional OCT can be used potentially to evaluate the retina and choroid with
      high agreement with EDI-OCT.

PMID- 30280002
TI  - A Comparative Analysis of the Fear of Falling Between Glaucoma and Age-Related
      Macular Degeneration Patients From a Developing Country.
AB  - Purpose: Falls are very prevalent in the older population. Visually impaired
      elderly patients are prone to falls as the result of visual loss and ageing. The
      purpose of the study was to compare the fear of falling (FoF) between primary
      open angle glaucoma (POAG) and age-related macular degeneration (ARMD) patients
      who live in a developing country. Methods: This was a cross-sectional
      observational study. After a complete eye examination including measurement of
      best-corrected visual acuity, ophthalmoscopy, and automated visual field, all
      subjects completed the Fall Efficacy Scale International Brazil (FES-I-Brazil)
      questionnaire. Results: The sample comprised 64 patients with POAG, 48 with ARMD,
      and 52 controls. All groups were matched for age, sex, comorbidity, and ethnic
      distribution. The FES-I score was 24.6 +/- 8.7, 25.3 +/- 6.3, and 24.2 +/- 7.7
      for glaucoma, ARMD, and controls, respectively (P = 0.894). A post hoc analysis
      comparing all subjects with advanced visual field defect (mean deviation [MD] < 
      12 dB) revealed a higher FES-I score in ARMD patients as compared to POAG ones
      (46.2 +/- 16.8 and 24.0 +/- 7.7 for ARMD and POAG, respectively, P < 0.001).
      Conclusion: In this cohort of elderly subjects with eye diseases, the FoF was
      similar among groups; however, ARMD patients with more compromised visual field
      had higher FoF as compared to POAG patients and controls. Translational
      Relevance: A high rate of fear of falling exists in ARMD patients with
      compromised visual field. This finding may be useful in developing
      multidimensional strategies to decrease fear of falling and improve quality of
      life in older persons living in a developing country.

PMID- 30280003
TI  - Effect of Ultrasonic Moisture Glasses on Dry Eye Signs and Symptoms.
AB  - Purpose: This study was undertaken to evaluate the effect of a novel humidifying
      eyeglass-shaped device-ultrasonic moisture glasses-on dry eye signs and symptoms.
      Methods: A total of 18 subjects with dry eye symptoms underwent a crossover test.
      A water cartridge was set on each temple of the eyeglass-shaped device. All
      subjects randomly wore the device twice in different settings, each for 10
      minutes. Subjects wore the glasses once with the cartridges filled with water
      (the intervention group), and once with the cartridges empty (the control group).
      The order was randomized. We evaluated tear film break-up time (TBUT) and
      fluorescein staining score just before, immediately after, and 10 minutes after
      wearing the device. We also assessed functional visual acuity (FVA), blink
      frequency, and visual analog scale (VAS) score just before and immediately after
      wearing the device. Results: TBUT, blink frequency, and VAS improved in the
      intervention group (all P < 0.001) and exhibited significant differences between
      the intervention and control groups. Conclusions: Wearing the ultrasonic moisture
      glasses for 10 minutes improved tear stability and decreased dry eye symptoms in
      this cohort of subjects. Translational Relevance: These findings show that the
      ultrasonic moisture glasses are an effective device for improving dry eye signs
      and symptoms.

PMID- 30280004
TI  - Prevalence of Subclinical CNV and Choriocapillaris Nonperfusion in Fellow Eyes of
      Unilateral Exudative AMD on OCT Angiography.
AB  - Purpose: To determine the prevalence of subclinical choroidal neovascularization
      (CNV) in fellow eyes of patients with unilateral exudative age-related macular
      degeneration (AMD) using optical coherence tomography angiography (OCTA) and to
      quantify choriocapillaris nonperfusion adjacent to CNV. Methods: We
      retrospectively reviewed all patients with AMD who underwent OCTA and identified
      eyes with unilateral exudative AMD. We determined the presence of subclinical CNV
      on custom en face macular slabs of the outer retina and choriocapillaris and
      confirmed on cross-sectional scans. Two graders quantified the percent
      choriocapillaris area of nonperfusion (PCAN) in the entire choriocapillaris slab
      as well as in the "halo" zone (200 MUm) surrounding subclinical and exudative CNV
      lesions. Results: Of 140 AMD patients who underwent OCTA, 34 had unilateral
      exudative AMD, with five of the 34 fellow eyes (14.7%) having subclinical CNV.
      Compared with PCAN in the entire slab (10.333 +/- 4.288%), we found that "halo"
      PCAN, surrounding CNV, was significantly higher (13.045 +/- 5.809%; P < 0.001).
      Further, there was a trend for higher PCAN in exudative CNV eyes (15.267 +/-
      7.230%) compared with their fellow subclinical CNV eyes (10.823 +/- 3.365%, P =
      0.115). Conclusions: There is a notable prevalence of subclinical CNV in fellow
      eyes with unilateral exudative CNV, and significantly greater choriocapillaris
      nonperfusion adjacent to all CNV lesions. We identified a trend for increased
      choriocapillaris nonperfusion in exudative AMD eyes as compared with their fellow
      subclinical CNV eyes, which deserves further study. Translational Relevance: OCTA
      can be useful in clinical practice to detect subclinical CNV and study
      choriocapillaris dysfunction.

PMID- 30280005
TI  - Variability of Foveal Avascular Zone Metrics Derived From Optical Coherence
      Tomography Angiography Images.
AB  - Purpose: To characterize sources of inter- and intrasubject variability in
      quantitative foveal avascular zone (FAZ) metrics. Methods: Two 3*3-mm optical
      coherence tomography angiography scans (centered on the fovea) were acquired in
      both eyes of 175 subjects. An image of the superficial plexus was extracted from
      each scan and segmented twice by a single observer. Four quantitative FAZ
      morphology metrics (area, axis ratio, acircularity, major horizontal axis angle)
      were calculated, and a variance components analysis was performed. Results: Mean
      (+/-SD) age was 27.9 +/- 11.9 years, and 55% were female. Area had the largest
      amount of variance resulting from intersubject differences (93.1%). In contrast,
      there was large interocular variance for axis ratio, acircularity, and major
      horizontal axis angle (55.0%, 53.7%, 70.7%, respectively), though only axis ratio
      showed significant asymmetry between fellow eyes (P < 0.05). Neither repeated
      images from the same eye nor repeated segmentation on the same image were
      significant sources of variance. Conclusions: Metrics of FAZ morphology show
      excellent repeatability and reliability. Excluding FAZ area, there was a high
      amount of variance attributed to interocular differences for the other FAZ
      metrics; therefore, the fellow eye should not be considered a control for FAZ
      studies when using these metrics. Translational Relevance: Vision scientists must
      be prudent when choosing FAZ metrics, as they display varying degrees of within
      subject differences relative to between-subject differences. It seems likely that
      different metrics will be best suited for different tasks, such as monitoring
      small changes over time within a single subject or assessing whether a given FAZ
      is abnormal.

PMID- 30280006
TI  - A Smartphone-Based Tool for Rapid, Portable, and Automated Wide-Field Retinal
      Imaging.
AB  - Purpose: High-quality, wide-field retinal imaging is a valuable method for
      screening preventable, vision-threatening diseases of the retina. Smartphone
      based retinal cameras hold promise for increasing access to retinal imaging, but
      variable image quality and restricted field of view can limit their utility. We
      developed and clinically tested a smartphone-based system that addresses these
      challenges with automation-assisted imaging. Methods: The system was designed to
      improve smartphone retinal imaging by combining automated fixation guidance,
      photomontage, and multicolored illumination with optimized optics, user-tested
      ergonomics, and touch-screen interface. System performance was evaluated from
      images of ophthalmic patients taken by nonophthalmic personnel. Two masked
      ophthalmologists evaluated images for abnormalities and disease severity.
      Results: The system automatically generated 100 degrees  retinal photomontages
      from five overlapping images in under 1 minute at full resolution (52.3 pixels
      per retinal degree) fully on-phone, revealing numerous retinal abnormalities.
      Feasibility of the system for diabetic retinopathy (DR) screening using the
      retinal photomontages was performed in 71 diabetics by masked graders. DR grade
      matched perfectly with dilated clinical examination in 55.1% of eyes and within 1
      severity level for 85.2% of eyes. For referral-warranted DR, average sensitivity
      was 93.3% and specificity 56.8%. Conclusions: Automation-assisted imaging
      produced high-quality, wide-field retinal images that demonstrate the potential
      of smartphone-based retinal cameras to be used for retinal disease screening.
      Translational Relevance: Enhancement of smartphone-based retinal imaging through
      automation and software intelligence holds great promise for increasing the
      accessibility of retinal screening.

PMID- 30280008
TI  - Correction: Accumulation and expression of horizontally acquired genes in
      Arcobacter cryaerophilus that thrives in sewage.
AB  - [This corrects the article DOI: 10.7717/peerj.3269.].

PMID- 30280007
TI  - Differences in Static and Kinetic Perimetry Results are Eliminated in Retinal
      Disease when Psychophysical Procedures are Equated.
AB  - Purpose: We tested the hypothesis that clinical statokinetic dissociation (SKD,
      defined as the difference in sensitivity to static and kinetic stimuli) at the
      scotoma border in retinal disease is due to individual criterion bias and that
      SKD can be eliminated by equating the psychophysical procedures for testing
      static and kinetic stimulus detection. Methods: Six subjects with glaucoma and
      six with retinitis pigmentosa (RP) were tested. Clinical procedures (standard
      automated perimetry [SAP] and manual kinetic perimetry [MKP]) were used to
      determine clinical SKD and the region of interest for laboratory-based testing.
      Two-way Method of Limits (MoL) was used to establish the isocontrast region at
      the scotoma border in glaucoma and RP subjects. Method of Constant Stimuli (MoCS)
      and a two-interval forced choice (2IFC) procedure then were used to present
      static or kinetic (inward or outward) stimuli at different eccentricities within
      the isocontrast region. The results were fitted with psychometric functions to
      determine threshold eccentricities. Results: Clinical SKD was found in glaucoma
      and RP subjects, with variable magnitude among subjects, but significantly
      exceeding expected typical measurement variability. The resultant psychometric
      functions when using MoCS and 2IFC showed equal sensitivity to static and kinetic
      targets, thus eliminating SKD. Conclusions: Clinical SKD found using clinical
      techniques is due to methodologic differences and criterion bias, and is
      eliminated by using an equated and more objective psychophysical task, similar to
      normal subjects. Translational relevance: Eliminating SKD using a psychophysical
      approach minimizing criterion bias suggests that it is not useful to distinguish
      between normal and diseased fields.

PMID- 30280010
TI  - Effectiveness of winter temperatures for satisfying chilling requirements for
      reproductive budburst of red alder (Alnus rubra).
AB  - Background: Experiencing an adequate amount of cold temperatures over winter is
      necessary for many temperate tree species to break dormancy and flower in spring.
      Thus, changes in winter and spring temperatures associated with climate change
      may influence when trees break dormancy and flower in the future. There have been
      several experimental studies that have quantified the effectiveness of cold
      temperatures for chilling requirements for vegetative budburst of temperate
      trees; however, there are few experimental studies addressing the chilling
      requirements for reproductive budburst of trees, as it is difficult to place
      reproductively mature trees in temperature-controlled environments. Methods: To
      identify how changing temperatures associated with climate change may impact
      reproductive phenology, we completed a temperature-controlled growth chamber
      experiment using cuttings of reproductive branches of red alder (Alnus rubra),
      one of the most widespread hardwood tree species of the Pacific Northwest, USA.
      The purpose of this study was to examine how colder (4  degrees C) and warmer (9 
      degrees C) winter temperature regimes influenced the timing of reproductive
      budburst of red alder cuttings in spring. We also compared the date of budburst
      of cuttings to that of branches from intact trees. Results: We found that
      cuttings flowered earlier after pretreatment with a 4  degrees C winter
      temperature regime than after a 9  degrees C winter temperature regime. We found
      no significant differences between the timing of male budburst of cuttings
      exposed to ambient conditions compared to male budburst of branches from intact
      trees. We used our experimental data to estimate a "possibility-line" that shows
      the accumulated chilling and forcing temperatures necessary prior to reproductive
      budburst of red alder. Discussion: This study provides a preliminary indication
      that warmer winters with climate change may not be as effective as colder winters
      for satisfying chilling temperature requirements of a Northwest hardwood tree
      species.

PMID- 30280011
TI  - New records of the archaic dolphin Agorophius (Mammalia: Cetacea) from the upper
      Oligocene Chandler Bridge Formation of South Carolina, USA.
AB  - The stem odontocete Agorophius pygmaeus (Ashley Formation, lower Oligocene, South
      Carolina; 29.0-26.57 Ma) has been a critical point of comparison for studies of
      early neocete evolution owing to its early discovery as well as its transitional
      anatomy relative to archaeocete whales and modern odontocetes. Some time during
      the late nineteenth century the holotype skull went missing and has never been
      relocated; supplementary reference specimens have since been recently referred to
      the species from the Ashley Formation and the overlying Chandler Bridge Formation
      (upper Oligocene; 24.7-23.5). New crania referable to Agorophius sp. are
      identifiable to the genus based on several features of the intertemporal region.
      Furthermore, all published specimens from the Chandler Bridge Formation
      consistently share larger absolute size and a proportionally shorter exposure of
      the parietal in the skull roof than specimens from the Ashley Formation
      (including the holotype). Furthermore, these specimens include well-preserved
      ethmoid labyrinths and cribriform plates, indicating that Agorophius primitively
      retained a strong olfactory sense. These new crania suggest that at least two
      species of Agorophius are present in the Oligocene of South Carolina, revealing a
      somewhat more complicated taxonomic perspective.

PMID- 30280009
TI  - Using bioinformatics tools for the discovery of Dengue RNA-dependent RNA
      polymerase inhibitors.
AB  - Background: Dengue fever has rapidly manifested into a serious global health
      concern. The emergence of various viral serotypes has prompted the urgent need
      for innovative drug design techniques. Of the viral non-structural enzymes, the
      NS5 RNA-dependent RNA polymerase has been established as a promising target due
      to its lack of an enzymatic counterpart in mammalian cells and its conserved
      structure amongst all serotypes. The onus is now on scientists to probe further
      into understanding this enzyme and its mechanism of action. The field of
      bioinformatics has evolved greatly over recent decades, with updated drug design
      tools now being publically available. Methods: In this study, bioinformatics
      tools were used to provide a comprehensive sequence and structural analysis of
      the two most prominent serotypes of Dengue RNA-dependent RNA polymerase. A list
      of popular flavivirus inhibitors were also chosen to dock to the active site of
      the enzyme. The best docked compound was then used as a template to generate a
      pharmacophore model that may assist in the design of target-specific Dengue virus
      inhibitors. Results: Comparative sequence alignment exhibited similarity between
      all three domains of serotype 2 and 3.Sequence analysis revealed highly conserved
      regions at residues Meth530, Thr543 Asp597, Glu616, Arg659 and Pro671. Mapping of
      the active site demonstrated two highly conserved residues: Ser710 and Arg729. Of
      the active site interacting residues, Ser796 was common amongst all ten docked
      compounds, indicating its importance in the drug design process. Of the ten
      docked flavivirus inhibitors, NITD-203 showed the best binding affinity to the
      active site. Further pharmacophore modeling of NITD-203 depicted significant
      pharmacophoric elements that are necessary for stable binding to the active site.
      Discussion: This study utilized publically available bioinformatics tools to
      provide a comprehensive framework on Dengue RNA-dependent RNA polymerase. Based
      on docking studies, a pharmacophore model was also designed to unveil the crucial
      pharmacophoric elements that are required when constructing an efficacious DENV
      inhibitor. We believe that this study will be a cornerstone in paving the road
      toward the design of target-specific inhibitors against DENV RdRp.

PMID- 30280013
TI  - Assessing bird avoidance of high-contrast lights using a choice test approach:
      implications for reducing human-induced avian mortality.
AB  - Background: Avian collisions with man-made objects and vehicles (e.g., buildings,
      cars, airplanes, power lines) have increased recently. Lights have been proposed
      to alert birds and minimize the chances of collisions, but it is challenging to
      choose lights that are tuned to the avian eye and can also lead to avoidance
      given the differences between human and avian vision. We propose a choice test to
      address this problem by first identifying wavelengths of light that would over
      stimulate the retina using species-specific perceptual models and by then
      assessing the avoidance/attraction responses of brown-headed cowbirds to these
      lights during daytime using a behavioral assay. Methods: We used perceptual
      models to estimate wavelength-specific light emitting diode (LED) lights with
      high chromatic contrast. The behavioral assay consisted of an arena where the
      bird moved in a single direction and was forced to make a choice (right/left)
      using a single-choice design (one side with the light on, the other with the
      light off) under diurnal light conditions. Results: First, we identified lights
      with high saliency from the cowbird visual perspective: LED lights with peaks at
      380 nm (ultraviolet), 470 nm (blue), 525 nm (green), 630 nm (red), and broad
      spectrum (white) LED lights. Second, we found that cowbirds significantly avoided
      LED lights with peaks at 470 and 630 nm, but did not avoid or prefer LED lights
      with peaks at 380 and 525 nm or white lights. Discussion: The two lights avoided
      had the highest chromatic contrast but relatively lower levels of achromatic
      contrast. Our approach can optimize limited resources to narrow down wavelengths
      of light with high visual saliency for a target species leading to avoidance.
      These lights can be used as candidates for visual deterrents to reduce collisions
      with man-made objects and vehicles.

PMID- 30280015
TI  - First record of Holothuria (Metriatyla) scabra Jaeger, 1833 (Echinodermata:
      Holothuroidea) from the coastal waters of the United Arab Emirates.
AB  - The presence of an endangered and economically valuable species of sea cucumber,
      Holothuria (Metriatyla) scabra Jaeger, 1833, was investigated in the Alqurm Wa
      Lehhfaiiah Protected Area near the city of Kalba in the Emirate of Sharjah. Sea
      cucumber specimens were collected, and identification was first conducted using
      morphological keys. H. scabra identification was confirmed through microscopic
      observation of ossicles. Though this species is known to occur in other regions
      along the Gulf of Oman, this paper represents the first published record of H.
      scabra, in the coastal waters of the United Arab Emirates.

PMID- 30280014
TI  - Leaf photosynthetic function duration during yield formation of large-spike wheat
      in rainfed cropping systems.
AB  - Improving photosynthetic capacity significantly affects the yield of wheat
      (Triticum aestivum L.) in rainfed regions. In this study, the physiological
      characteristics of eight large-spike wheat lines were compared with a multiple
      spike cultivar as a control (CK) in a field over two consecutive seasons: 2010
      2012. The tillering peak was 7-21 d after returning green for line 2040, the
      average rate of decline of relative water content was slower, and the average
      duration time of photosynthetic rate was longer than CK in vitro. There was a
      strong linear and positive correlation between photosynthetic rate and root
      activity at jointing, flowering, and grain-filling stages. In addition, average
      yields were higher in large-spike lines than CK (multiple-spike cultivar). The
      results suggest that large-spike lines might have greater water retaining
      capacity during yield formation under rainfed conditions.

PMID- 30280012
TI  - Crystal structure and functional analysis of human C1ORF123.
AB  - Proteins of the DUF866 superfamily are exclusively found in eukaryotic cells. A
      member of the DUF866 superfamily, C1ORF123, is a human protein found in the open
      reading frame 123 of chromosome 1. The physiological role of C1ORF123 is yet to
      be determined. The only available protein structure of the DUF866 family shares
      just 26% sequence similarity and does not contain a zinc binding motif. Here, we
      present the crystal structure of the recombinant human C1ORF123 protein
      (rC1ORF123). The structure has a 2-fold internal symmetry dividing the monomeric
      protein into two mirrored halves that comprise of distinct electrostatic
      potential. The N-terminal half of rC1ORF123 includes a zinc-binding domain
      interacting with a zinc ion near to a potential ligand binding cavity. Functional
      studies of human C1ORF123 and its homologue in the fission yeast
      Schizosaccharomyces pombe (SpEss1) point to a role of DUF866 protein in
      mitochondrial oxidative phosphorylation.

PMID- 30280016
TI  - Morphometric traits in the fine-leaved fescues depend on ploidy level: the case
      of Festuca amethystina L.
AB  - Background: Polyploid specimens are usually characterized by greater exuberance:
      they reach larger sizes and/or have a larger number of some organs. Festuca
      amethystina L. belongs to the section Aulaxyper. Based on morphological features,
      four subspecies of F. amethystina have been already identified. On the other
      hand, it has two cytotypes: diploid and tetraploid. The main aim of our study was
      to distinguish morphological differences between the cytotypes of F. amethystina,
      assuming that its phenotype differs significantly. Methods: The nuclear DNA
      content was measured by flow cytometry in dry leaves from specimens originating
      from 13 populations of F. amethystina. Several macrometric and micrometric traits
      of stems, spikelets and leaf blades were taken into account in the comparative
      analysis of two cytotypes. Results: In the case of cytotypes, specimens of
      tetraploids were larger than diploids. The conducted morphometric analysis of
      leaf cross-sections showed significant differences between the cytotypes.
      Discussion: The research has confirmed for the first time that in the case of F.
      amethystina the principle of greater exuberance of polyploids is true.
      Differences between the cytotypes are statistically significant, however, they
      are not enough to make easy the distinction of cytotypes on the basis of the
      measurements themselves. Our findings favor the rule known in Festuca taxonomy as
      a whole, i.e. that the ploidy level can be one of the main classification
      criteria.

PMID- 30280017
TI  - Pre-imaginal conditioning alters adult sex pheromone response in Drosophila.
AB  - Pheromones are chemical signals that induce innate responses in individuals of
      the same species that may vary with physiological and developmental state. In
      Drosophila melanogaster, the most intensively studied pheromone is 11-cis
      vaccenyl acetate (cVA), which is synthezised in the male ejaculatory bulb and is
      transferred to the female during copulation. Among other effects, cVA inhibits
      male courtship of mated females. We found that male courtship inhibition depends
      on the amount of cVA and this effect is reduced in male flies derived from eggs
      covered with low to zero levels of cVA. This effect is not observed if the eggs
      are washed, or if the eggs are laid several days after copulation. This suggests
      that courtship suppression involves a form of pre-imaginal conditioning, which we
      show occurs during the early larval stage. The conditioning effect could not be
      rescued by synthetic cVA, indicating that it largely depends on conditioning by
      cVA and other maternally-transmitted factor(s). These experiments suggest that
      one of the primary behavioral effects of cVA is more plastic and less
      stereotypical than had hitherto been realised.

PMID- 30280018
TI  - Identification of an aquaculture poriferan "Pest with Potential" and its
      phylogenetic implications.
AB  - Correct identification and classification of sponges is challenging due to
      ambiguous or misleading morphological features. A particular case is a blue
      keratose sponge occasionally referred to as the "Blue Photo Sponge" among
      aquarists, which appears frequently (and in several cases unintended) in private
      aquaria. This spicule-less species, occasionally specified as Collospongia auris
      Bergquist, Cambie & Kernan 1990, not only displays a high phenotypic plasticity
      in growth form and colour, it also proliferates in aquacultures under standard
      conditions unlike most other sponges. Therefore, this species is regarded as a
      pest for most aquarists. In turn, the ease of cultivation and propagation in
      aquacultures qualifies this species as a model organism for a wide array of
      scientific applications. For these purposes, correct identification and
      classification are indispensable. We reconstructed ribosomal gene trees and
      determined this species as Lendenfeldia chondrodes (De Laubenfels, 1954)
      (Phyllospongiinae), distant to Collospongia auris, and corroborated by skeletal
      features. Additionally, the resulting phylogeny corroborated major shortcomings
      of the current Phyllospongiinae classification-its consequences are discussed.

PMID- 30280020
TI  - Different environmental gradients affect different measures of snake beta
      diversity in the Amazon rainforests.
AB  - Mechanisms generating and maintaining biodiversity at regional scales may be
      evaluated by quantifying beta-diversity along environmental gradients.
      Differences in assemblages result in biotic complementarities and redundancies
      among sites, which may be quantified through multi-dimensional approaches
      incorporating taxonomic beta-diversity (TBD), functional beta-diversity (FBD) and
      phylogenetic beta-diversity (PBD). Here we test the hypothesis that snake TBD,
      FBD and PBD are influenced by environmental gradients, independently of
      geographic distance. The gradients tested are expected to affect snake
      assemblages indirectly, such as clay content in the soil determining primary
      production and height above the nearest drainage determining prey availability,
      or directly, such as percentage of tree cover determining availability of resting
      and nesting sites, and climate (temperature and precipitation) causing
      physiological filtering. We sampled snakes in 21 sampling plots, each covering
      five km2, distributed over 880 km in the central-southern Amazon Basin. We used
      dissimilarities between sampling sites to quantify TBD, FBD and PBD, which were
      response variables in multiple-linear-regression and redundancy analysis models.
      We show that patterns of snake community composition based on TBD, FBD and PBD
      are associated with environmental heterogeneity in the Amazon. Despite positive
      correlations between all beta-diversity measures, TBD responded to different
      environmental gradients compared to FBD and PBD. Our findings suggest that multi
      dimensional approaches are more informative for ecological studies and
      conservation actions compared to a single diversity measure.

PMID- 30280021
TI  - Finding wolf homesites: improving the efficacy of howl surveys to study wolves.
AB  - Locating wolf (Canis lupus) homesites is valuable for understanding the foraging
      behavior, population dynamics, and reproductive ecology of wolves during summer.
      During this period wolf pack members (adults and pups) readily respond to
      simulated wolf howls (i.e., howl surveys), which allows researchers to estimate
      the location of the homesite via triangulation. Confirming the actual locations
      of homesites via ground truthing is labor intensive because of the error
      surrounding estimated locations. Our objectives were (1) to quantify observer
      error during howl surveys and compare amongst experience levels, (2) provide a
      simple method for locating homesites in the field by incorporating observer
      error, and (3) further document the value of this method for monitoring wolf
      packs throughout the summer. We located 17 homesites by howl surveys during 2015
      2017 in the Greater Voyageurs Ecosystem, Minnesota, USA. Of 62 bearings taken by
      observers during howl surveys, bearings erred by an average of 7.6 degrees  +/-
      6.3 degrees  (SD). There was no difference in observer error between novice and
      experienced observers. A simple way to increase efficiency when searching for
      homesites is to search concentric areas (bands) based on estimated observer
      error, specifically by: (1) adding +/-10 degrees  error bands around howl survey
      bearings when >=3 bearings can be obtained, (2) +/-10 degrees  and +/-20 degrees 
      error bands when 2 bearings are obtained, and (3) +/-10 degrees  and +/-26
      degrees  error bands when 1 bearing is obtained. By incorporating observer error
      and understanding how frequently and how far wolves move homesites, it is
      possible to monitor wolf packs and confirm most, if not all, homesites used by a
      pack from at least June until August without having a collared individual in a
      pack.

PMID- 30280019
TI  - E-cigarettes versus nicotine patches for perioperative smoking cessation: a pilot
      randomized trial.
AB  - Introduction: Cigarette smoking by surgical patients is associated with increased
      complications. E-cigarettes have emerged as a potential smoking cessation tool.
      We sought to determine the feasibility and acceptability of e-cigarettes,
      compared to nicotine patch, for perioperative smoking cessation in veterans.
      Methods: Preoperative patients were randomized to either the nicotine patch group
      (n = 10) or the e-cigarette group (n = 20). Both groups were given a free 6-week
      supply in a tapering dose. All patients received brief counseling, a brochure on
      perioperative smoking cessation, and referral to the California Smokers'
      Helpline. The primary outcome was rate of smoking cessation on day of surgery
      confirmed by exhaled carbon monoxide. Secondary outcomes included smoking habits,
      pulmonary function, adverse events, and satisfaction with the products on day of
      surgery and at 8-weeks follow-up. Results: Biochemically verified smoking
      cessation on day of surgery was similar in both groups. Change in forced
      expiratory volume in one second (FEV1) was 592 ml greater in the e-cigarette
      group (95% CI [153-1,031] ml, p = 0.01) and change in forced expiratory volume in
      one second to forced vital capacity ratio (FEV1/FVC ratio) was 40.1% greater in
      the e-cigarette group (95% CI [18.2%-78.4%], p = 0.04). Satisfaction with the
      product was similar in both groups. Discussion: E-cigarettes are a feasible tool
      for perioperative smoking cessation in veterans with quit rates comparable to
      nicotine replacement patch. Spirometry appears to be improved 8-weeks after
      initiating e-cigarettes compared to nicotine patch, possibly due to worse
      baseline spirometry and more smoking reduction in the e-cigarette group. An
      adequately powered study is recommended to determine if these results can be
      duplicated.

PMID- 30280022
TI  - Functional responses of a cosmopolitan invader demonstrate intraspecific
      variability in consumer-resource dynamics.
AB  - Background: Variability in the ecological impacts of invasive species across
      their geographical ranges may decrease the accuracy of risk assessments.
      Comparative functional response analysis can be used to estimate invasive
      consumer-resource dynamics, explain impact variability, and thus potentially
      inform impact predictions. The European green crab (Carcinus maenas) has been
      introduced on multiple continents beyond its native range, although its
      ecological impacts appear to vary among populations and regions. Our aim was to
      test whether consumer-resource dynamics under standardized conditions are
      similarly variable across the current geographic distribution of green crab, and
      to identify correlated morphological features. Methods: Crabs were collected from
      multiple populations within both native (Northern Ireland) and invasive regions
      (South Africa and Canada). Their functional responses to local mussels (Mytilus
      spp.) were tested. Attack rates and handling times were compared among green crab
      populations within each region, and among regions (Pacific Canada, Atlantic
      Canada, South Africa, and Northern Ireland). The effect of predator and prey
      morphology on prey consumption was investigated. Results: Across regions, green
      crabs consumed prey according to a Type II (hyperbolic) functional response
      curve. Attack rates (i.e., the rate at which a predator finds and attacks prey),
      handling times and maximum feeding rates differed among regions. There was a
      trend toward higher attack rates in invasive than in native populations. Green
      crabs from Canada had lower handling times and thus higher maximum feeding rates
      than those from South Africa and Northern Ireland. Canadian and Northern Ireland
      crabs had significantly larger claws than South African crabs. Claw size was a
      more important predictor of the proportion of mussels killed than prey shell
      strength. Discussion: The differences in functional response between regions
      reflect observed impacts of green crabs in the wild. This suggests that an
      understanding of consumer-resource dynamics (e.g., the per capita measure of
      predation), derived from simple, standardized experiments, might yield useful
      predictions of invader impacts across geographical ranges.

PMID- 30280023
TI  - Successful transplantation of guinea pig gut microbiota in mice and its effect on
      pneumonic plague sensitivity.
AB  - Microbiota-driven variations in the inflammatory response are predicted to
      regulate host responses to infection. Increasing evidence indicates that the
      gastrointestinal and respiratory tracts have an intimate relationship with each
      other. Gut microbiota can influence lung immunity whereby gut-derived injurious
      factors can reach the lungs and systemic circulation via the intestinal
      lymphatics. The intestinal microbiota's ability to resist colonization can be
      extended to systemic infections or to pathogens infecting distant sites such as
      the lungs. Unlike the situation with large mammals, the microtus Yersinia pestis
      201 strain exhibits strong virulence in mice, but nearly no virulence to large
      mammals (such as guinea pigs). Hence, to assess whether the intestinal microbiota
      from guinea pigs was able to affect the sensitivity of mice to challenge
      infection with the Y. pestis 201 strain, we fed mice with guinea pig diets for
      two months, after which they were administered 0.5 ml of guinea pig fecal
      suspension for 30 days by oral gavage. The stools from each mouse were collected
      on days 0, 15, and 30, DNA was extracted from them, and 16S rRNA sequencing was
      performed to assess the diversity and composition of the gut microbiota. We found
      that the intestinal microbiota transplants from the guinea pigs were able to
      colonize the mouse intestines. The mice were then infected with Yersinia pestis
      201 by lung invasion, but no statistical difference was found in the survival
      rates of the mice that were colonized with the guinea pig's gut microbiota and
      the control mice. This indicates that the intestinal microbiota transplantation
      from the guinea pigs did not affect the sensitivity of the mice to pneumonic
      plague.

PMID- 30280024
TI  - Analysis of relative abundances with zeros on environmental gradients: a
      multinomial regression model.
AB  - Ecologists often analyze relative abundances, which are an example of
      compositional data. However, they have made surprisingly little use of recent
      advances in the field of compositional data analysis. Compositions form a vector
      space in which addition and scalar multiplication are replaced by operations
      known as perturbation and powering. This algebraic structure makes it easy to
      understand how relative abundances change along environmental gradients. We
      illustrate this with an analysis of changes in hard-substrate marine communities
      along a depth gradient. We fit a quadratic multivariate regression model with
      multinomial observations to point count data obtained from video transects. As
      well as being an appropriate observation model in this case, the multinomial
      deals with the problem of zeros, which often makes compositional data analysis
      difficult. We show how the algebra of compositions can be used to understand
      patterns in dissimilarity. We use the calculus of simplex-valued functions to
      estimate rates of change, and to summarize the structure of the community over a
      vertical slice. We discuss the benefits of the compositional approach in the
      interpretation and visualization of relative abundance data.

PMID- 30280025
TI  - Dynamics of nitrogen and active nitrogen components across seasons under varying
      stand densities in a Larix principis-rupprechtii (Pinaceae) plantation.
AB  - Changes in the concentration of soil nitrogen (N) or its components may directly
      affect ecosystem functioning in forestry. Thinning of forest stands, a widely
      used forestry management practice, may transform soil nutrients directly by
      altering the soil environment, or indirectly by changing above- or belowground
      plant biomass. The study objectives were to determine how tree stem density
      affects the soil N pool and what mechanisms drive any potential changes. In this
      study, N and its active components were measured in the soil of a Larix principis
      rupprechtii plantation across two full growing seasons, in 12 (25 * 25 m) plots:
      (low thinning, removal of 15% of the trees, three plot repetitions), moderate
      thinning (MT) (35% removal) and heavy thinning (HT) (50% removal) and no thinning
      control. Environmental indices, like the light condition, soil respiration, soil
      temperatures, and prescription, were measured in the plots also. Results
      indicated that soil total nitrogen (STN) was affected by tree stem density
      adjustments in the short-term; STN generally increased with decreasing tree stem
      density, reaching its highest concentration in the MT treatment before decreasing
      in HT. This pattern was echoed by the DON/STN ratio dissolved organic nitrogen
      (DON) under MT. A lower DON/STN was measured across the seasons. Microbial
      biomass nitrogen (MBN) and the SOC/STN (soil organic carbon (SOC)) ratio and
      density treatments influenced MBN concentration and inhibited SOC/STN. MT tended
      to accumulate more STN, produce lower DON/STN and had a generally higher
      microbial activity, which may be partly ascribed to the higher MBN value, MBN/STN
      ratio and lower DON/STN. The water conditions (soil moisture), light and soil
      temperatures could partly be responsible for the N pool dynamic in the different
      density treatments.

PMID- 30280026
TI  - Variation of soil bacterial communities along a chronosequence of Eucalyptus
      plantation.
AB  - Eucalyptus is harvested for wood and fiber production in many tropical and sub
      tropical habitats globally. Plantation has been controversial because of its
      influence on the surrounding environment, however, the influence of massive
      Eucalyptus planting on soil microbial communities is unclear. Here we applied
      high-throughput sequencing of the 16S rRNA gene to assess the microbial community
      composition and diversity of planting chronosequences, involving two, five and
      ten years of Eucalyptus plantation, comparing to that of secondary-forest in
      South China. We found that significant changes in the composition of soil
      bacteria occurred when the forests were converted from secondary-forest to
      Eucalyptus. The bacterial community structure was clearly distinct from control
      and five year samples after Eucalyptus was grown for 2 and 10 years, highlighting
      the influence of this plantation on local soil microbial communities. These
      groupings indicated a cycle of impact (2 and 10 year plantations) and low impact
      (5-year plantations) in this chronosequence of Eucalyptus plantation. Community
      patterns were underpinned by shifts in soil properties such as pH and phosphorus
      concentration. Concurrently, key soil taxonomic groups such as Actinobacteria
      showed abundance shifts, increasing in impacted plantations and decreasing in low
      impacted samples. Shifts in taxonomy were reflected in a shift in metabolic
      potential, including pathways for nutrient cycles such as carbon fixation, which
      changed in abundance over time following Eucalyptus plantation. Combined these
      results confirm that Eucalyptus plantation can change the community structure and
      diversity of soil microorganisms with strong implications for land-management and
      maintaining the health of these ecosystems.

PMID- 30280028
TI  - Xeno-miRNet: a comprehensive database and analytics platform to explore xeno
      miRNAs and their potential targets.
AB  - Xeno-miRNAs are microRNAs originating from exogenous species detected in host
      biofluids. A growing number of studies have suggested that many of these xeno
      miRNAs may be involved in cross-species interactions and manipulations. To date,
      hundreds of xeno-miRNAs have been reported in different hosts at various
      abundance levels. Based on computational predictions, many more miRNAs could be
      potentially transferred to human circulation system. There is a clear need for
      bioinformatics resources and tools dedicated to xeno-miRNA annotations and their
      potential functions. To address this need, we have systematically curated xeno
      miRNAs from multiple sources, performed target predictions using well-established
      algorithms, and developed a user-friendly web-based tool-Xeno-miRNet-to allow
      researchers to search and explore xeno-miRNAs and their potential targets within
      different host species. Xeno-miRNet currently contains 1,702 (including both
      detected and predicted) xeno-miRNAs from 54 species and 98,053 potential gene
      targets in six hosts. The web application is freely available at
      http://xeno.mirnet.ca.

PMID- 30280029
TI  - Closing the gap: mixed stock analysis of three foraging populations of green
      turtles (Chelonia mydas) on the Great Barrier Reef.
AB  - A solid understanding of the spatial ecology of green turtles (Chelonia mydas) is
      fundamental to their effective conservation. Yet this species, like many marine
      migratory species, is challenging to monitor and manage because they utilise a
      variety of habitats that span wide spatio-temporal scales. To further elucidate
      the connectivity between green turtle rookeries and foraging populations, we
      sequenced the mtDNA control region of 278 turtles across three foraging sites
      from the northern Great Barrier Reef (GBR) spanning more than 330 km: Cockle Bay,
      Green Island and Low Isles. This was performed with a newly developed assay,
      which targets a longer fragment of mtDNA than previous studies. We used a mixed
      stock analysis (MSA), which utilises genetic data to estimate the relative
      proportion of genetically distinct breeding populations found at a given foraging
      ground. Haplotype and nucleotide diversity was also assessed. A total of 35
      haplotypes were identified across all sites, 13 of which had not been found
      previously in any rookery. The MSA showed that the northern GBR (nGBR), Coral Sea
      (CS), southern GBR (sGBR) and New Caledonia (NC) stocks supplied the bulk of the
      turtles at all three sites, with small contributions from other rookeries in the
      region. Stock contribution shifted gradually from north to south, although
      sGBR/CS stock dominated at all three sites. The major change in composition
      occured between Cockle Bay and Low Isles. Our findings, together with other
      recent studies in this field, show that stock composition shifts with latitude as
      a natural progression along a coastal gradient. This phenomenon is likely to be
      the result of ocean currents influencing both post-hatchling dispersal and
      subsequent juvenile recruitment to diverse coastal foraging sites.

PMID- 30280030
TI  - New mud dragons from Svalbard: three new species of Cristaphyes and the first
      Arctic species of Pycnophyes (Kinorhyncha: Allomalorhagida: Pycnophyidae).
AB  - Background: Kinorhynchs are marine, microscopic invertebrates inhabiting the
      seafloors. Their segmented trunk equipped with spines and processes has inspired
      scientists to give them the common name "mud dragons." Even though kinorhynchs
      have been known since the 19th century, less than 300 species are known to
      science, and it is still considered a largely understudied animal group-in
      particular in the Arctic, from which only 23 species are known so far. Methods:
      Samples were collected at eight stations around Svalbard and in the fjords of
      Spitsbergen. Meiofauna was extracted from the sediment cores with LUDOX
      centrifugation method, and kinorhynchs were picked up and mounted for light- and
      scanning electron microscopy. Results: Four new species of the kinorhynch family
      Pycnophyidae are described from Svalbard: Cristaphyes dordaidelosensis sp. nov.,
      C. glaurung sp. nov., C. scatha sp. nov., and Pycnophyes ancalagon sp. nov. The
      new species are generally recognized by their distribution of setae along the
      trunk segments. Discussion: After the discovery of the new species, Pycnophyidae
      becomes with 14 species the most diverse kinorhynch genus in the Arctic, closely
      followed by Echinoderidae with 13 species. So far, these are the only kinorhynch
      families with an Arctic distribution.

PMID- 30280027
TI  - Molecular analysis of oral microflora in patients with primary Sjogren's syndrome
      by using high-throughput sequencing.
AB  - Background: The objective of this study was to characterize the oral microflora
      profile of primary Sjogren's syndrome (pSS) patients, thereby revealing the
      connection between oral bacterial composition and dental caries, and to identify
      the "core microbiome" in the oral cavities of pSS patients and systemic healthy
      individuals by using a high-throughput sequencing technique. Methods: Twenty-two
      pSS patients and 23 healthy controls were enrolled in this study. Their clinical
      data and oral rinse samples were collected. The V3-V4 hypervariable regions of
      the bacterial 16S rRNA gene of samples were amplified and analyzed by high
      throughput sequencing on the Illumina Miseq PE300 platform. Results: Both two
      groups were age- and sex-matched. There were significantly higher decayed,
      missing and filled teeth (DMFT) and decayed, missing and filled surfaces (DMFS)
      in the pSS group than in the control group (p < 0.01). Alpha diversity was
      depleted in pSS patients, compared with healthy controls (p < 0.01), while beta
      diversity between the two groups was not significantly different. Seven
      discriminative genera (LDA > 4) were found between the two groups in LEfSe (LDA
      Effect Size) analysis. The relative abundance of Veillonella in pSS patients was
      fourfold higher, while Actinomyces, Haemophilus, Neisseria, Rothia, Porphyromonas
      and Peptostreptococcus were significantly lower in pSS patients than in healthy
      controls. However, the correlation between Veillonella and DMFT/DMFS was not
      significant (p > 0.05). In Venn diagram analysis, nine genera shared by all
      samples of two groups, which comprised 71.88% and 67.64% in pSS patients and
      controls, respectively. Discussion: These findings indicate a microbial dysbiosis
      in pSS patients; notably, Veillonella might be recognized as a biomarker in pSS
      patients. The core microbiome in pSS patients was similar to the systemic healthy
      population. These provide insight regarding advanced microbial prevention and
      treatment of severe dental caries in pSS patients. This study also provides basic
      data regarding microbiology in pSS.

PMID- 30280032
TI  - Human dimensions of wildfires in NW Spain: causes, value of the burned vegetation
      and administrative measures.
AB  - Exploring the human dimensions of forest fires is a crucial, although often
      overlooked, aspect of wildfire research, since wildfires often have important
      socio-economic impacts and humans are nowadays the main cause of wildfires in
      many areas of the world. We carried out a telephone survey (N = 345 interviews)
      in one of the most fire-prone areas in Europe (NW Spain) in order to assess
      citizens' awareness about wildfire causes and risks, their perception of the
      value of the vegetation and of administrative measures to fight against fires.
      Perceptions of respondents about fire causes were in general realistic although
      fires caused by pyromaniacs and for profit were overestimated, while vegetation
      management was comparatively underestimated. Citizens were broadly aware of the
      fire risk associated with different vegetation types, rightly considering native
      oak forests and agricultural fields as less risky than shrublands and pine and
      eucalypt plantations. Tree-dominated vegetation was more valued than treeless
      formations, and native forests more than tree plantations, which seems related to
      a preference for ecological value over utilitarian considerations. In addition,
      the value of eucalypt plantations was clearly affected by the education level of
      respondents, being less valued as the education level increased. Most citizens
      considered that the administration was not doing enough to fight against fires.
      The law that compels landowners to reduce fuels in wildland-urban interfaces was
      considered effective by most respondents (72%), but 50% considered it difficult
      to implement by landowners. This may explain the poor degree of compliance of
      this law.

PMID- 30280031
TI  - Assessing the role of dispersed floral resources for managed bees in providing
      supporting ecosystem services for crop pollination.
AB  - Most pollination ecosystem services studies have focussed on wild pollinators and
      their dependence on natural floral resources adjacent to crop fields. However,
      managed pollinators depend on a mixture of floral resources that are spatially
      separated from the crop field. Here, we consider the supporting role these
      resources play as an ecosystem services provider to quantify the use and
      availability of floral resources, and to estimate their relative contribution to
      support pollination services of managed honeybees. Beekeepers supplying
      pollination services to the Western Cape deciduous fruit industry were
      interviewed to obtain information on their use of floral resources. For 120
      apiary sites, we also analysed floral resources within a two km radius of each
      site based on geographic data. The relative availability of floral resources at
      sites was compared to regional availability. The relative contribution of floral
      resources-types to sustain managed honeybees was estimated. Beekeepers showed a
      strong preference for eucalypts and canola. Beekeepers selectively placed more
      hives at sites with eucalypt and canola and less with natural vegetation.
      However, at the landscape-scale, eucalypt was the least available resource,
      whereas natural vegetation was most common. Based on analysis of apiary sites, we
      estimated that 700,818 ha of natural vegetation, 73,910 ha of canola fields, and
      10,485 ha of eucalypt are used to support the managed honeybee industry in the
      Western Cape. Whereas the Cape managed honeybee system uses a bee native to the
      region, alien plant species appear disproportionately important among the floral
      resources being exploited. We suggest that an integrated approach, including
      evidence from interview and landscape data, and fine-scale biological data is
      needed to study floral resources supporting managed honeybees.

PMID- 30280034
TI  - Effect of changes in the fractal structure of a littoral zone in the course of
      lake succession on the abundance, body size sequence and biomass of beetles.
AB  - Dystrophic lakes undergo natural disharmonic succession, in the course of which
      an increasingly complex and diverse, mosaic-like pattern of habitats evolves. In
      the final seral stage, the most important role is played by a spreading Sphagnum
      mat, which gradually reduces the lake's open water surface area. Long-term
      transformations in the primary structure of lakes cause changes in the structure
      of lake-dwelling fauna assemblages. Knowledge of the succession mechanisms in
      lake fauna is essential for proper lake management. The use of fractal concepts
      helps to explain the character of fauna in relation to other aspects of the
      changing complexity of habitats. Our 12-year-long study into the succession of
      water beetles has covered habitats of 40 selected lakes which are diverse in
      terms of the fractal dimension. The taxonomic diversity and density of lake
      beetles increase parallel to an increase in the fractal dimension. An in-depth
      analysis of the fractal structure proved to be helpful in explaining the
      directional changes in fauna induced by the natural succession of lakes. Negative
      correlations appear between the body size and abundance. An increase in the
      density of beetles within the higher dimension fractals is counterbalanced by a
      change in the size of individual organisms. As a result, the biomass is constant,
      regardless of the fractal dimension.

PMID- 30280033
TI  - High-throughput metabarcoding reveals the effect of physicochemical soil
      properties on soil and litter biodiversity and community turnover across
      Amazonia.
AB  - Background: Knowledge on the globally outstanding Amazonian biodiversity and its
      environmental determinants stems almost exclusively from aboveground organisms,
      notably plants. In contrast, the environmental factors and habitat preferences
      that drive diversity patterns for micro-organisms in the ground remain elusive,
      despite the fact that micro-organisms constitute the overwhelming majority of
      life forms in any given location, in terms of both diversity and abundance. Here
      we address how the diversity and community turnover of operational taxonomic
      units (OTU) of organisms in soil and litter respond to soil physicochemical
      properties; whether OTU diversities and community composition in soil and litter
      are correlated with each other; and whether they respond in a similar way to soil
      properties. Methods: We used recently inferred OTUs from high-throughput
      metabarcoding of the 16S (prokaryotes) and 18S (eukaryotes) genes to estimate OTU
      diversity (OTU richness and effective number of OTUs) and community composition
      for prokaryotes and eukaryotes in soil and litter across four localities in
      Brazilian Amazonia. All analyses were run separately for prokaryote and eukaryote
      OTUs, and for each group using both presence-absence and abundance data.
      Combining these with novel data on soil chemical and physical properties, we
      identify abiotic correlates of soil and litter organism diversity and community
      structure using regression, ordination, and variance partitioning analysis.
      Results: Soil organic carbon content was the strongest factor explaining OTU
      diversity (negative correlation) and pH was the strongest factor explaining
      community turnover for prokaryotes and eukaryotes in both soil and litter. We
      found significant effects also for other soil variables, including both chemical
      and physical properties. The correlation between OTU diversity in litter and in
      soil was non-significant for eukaryotes and weak for prokaryotes. The community
      compositions of both prokaryotes and eukaryotes were more separated among habitat
      types (terra-firme, varzea, igapo and campina) than between substrates (soil and
      litter). Discussion: In spite of the limited sampling (four localities, 39
      plots), our results provide a broad-scale view of the physical and chemical
      correlations of soil and litter biodiversity in a longitudinal transect across
      the world's largest rainforest. Our methods help to understand links between soil
      properties, OTU diversity patterns, and community composition and turnover. The
      lack of strong correlation between OTU diversity in litter and in soil suggests
      independence of diversity drives of these substrates and highlights the
      importance of including both measures in biodiversity assessments. Massive
      sequencing of soil and litter samples holds the potential to complement
      traditional biological inventories in advancing our understanding of the factors
      affecting tropical diversity.

PMID- 30280035
TI  - Wind-driven spume droplet production and the transport of Pseudomonas syringae
      from aquatic environments.
AB  - Natural aquatic environments such as oceans, lakes, and rivers are home to a
      tremendous diversity of microorganisms. Some may cross the air-water interface
      within droplets and become airborne, with the potential to impact the Earth's
      radiation budget, precipitation processes, and spread of disease. Larger droplets
      are likely to return to the water or adjacent land, but smaller droplets may be
      suspended in the atmosphere for transport over long distances. Here, we report on
      a series of controlled laboratory experiments to quantify wind-driven droplet
      production from a freshwater source for low wind speeds. The rate of droplet
      production increased quadratically with wind speed above a critical value (10-m
      equivalent 5.7 m/s) where droplet production initiated. Droplet diameter and
      ejection speeds were fit by a gamma distribution. The droplet mass flux and
      momentum flux increased with wind speed. Two mechanisms of droplet production,
      bubble bursting and fragmentation, yielded different distributions for diameter,
      speed, and angle. At a wind speed of about 3.5 m/s, aqueous suspensions of the
      ice-nucleating bacterium Pseudomonas syringae were collected at rates of 283
      cells m-2 s-1 at 5 cm above the water surface, and at 14 cells m-2 s-1 at 10 cm
      above the water surface. At a wind speed of about 4.0 m/s, aqueous suspensions of
      P. syringae were collected at rates of 509 cells m-2 s-1 at 5 cm above the water
      surface, and at 81 cells m-2 s-1 at 10 cm above the water surface. The potential
      for microbial flux into the atmosphere from aquatic environments was calculated
      using known concentrations of bacteria in natural freshwater systems. Up to 3.1 *
      104 cells m-2 s-1 of water surface were estimated to leave the water in
      potentially suspended droplets (diameters <100 um). Understanding the sources and
      mechanisms for bacteria to aerosolize from freshwater aquatic sources may aid in
      designing management strategies for pathogenic bacteria, and could shed light on
      how bacteria are involved in mesoscale atmospheric processes.

PMID- 30280036
TI  - Plurality in multi-disciplinary research: multiple institutional affiliations are
      associated with increased citations.
AB  - Background: The institutional affiliations and associated collaborative networks
      that scientists foster during their research careers are salient in the
      production of high-quality science. The phenomenon of multiple institutional
      affiliations and its relationship to research output remains relatively
      unexplored in the literature. Methods: We examined 27,612 scientific articles,
      modelling the normalized citation counts received against the number of authors
      and affiliations held. Results: In agreement with previous research, we found
      that teamwork is an important factor in high impact papers, with average
      citations received increasing concordant with the number of co-authors listed.
      For articles with more than five co-authors, we noted an increase in average
      citations received when authors with more than one institutional affiliation
      contributed to the research. Discussion: Multiple author affiliations may play a
      positive role in the production of high-impact science. This increased researcher
      mobility should be viewed by institutional boards as meritorious in the pursuit
      of scientific discovery.

PMID- 30280037
TI  - Tumor-preventing activity of aspirin in multiple cancers based on bioinformatic
      analyses.
AB  - Background: Acetylsalicylic acid was renamed aspirin in 1899, and it has been
      widely used for its multiple biological actions. Because of the diversity of the
      cellular processes and diseases that aspirin reportedly affects and benefits,
      uncertainty remains regarding its mechanism in different biological systems.
      Methods: The Drugbank and STITCH databases were used to find direct protein
      targets (DPTs) of aspirin. The Mentha database was used to analyze protein
      protein interactions (PPIs) to find DPT-associated genes. DAVID was used for the
      GO and KEGG enrichment analyses. The cBio Cancer Genomics Portal database was
      used to mine genetic alterations and networks of aspirin-associated genes in
      cancer. Results: Eighteen direct protein targets (DPT) and 961 DPT-associated
      genes were identified for aspirin. This enrichment analysis resulted in eight
      identified KEGG pathways that were associated with cancers. Analysis using the
      cBio portal indicated that aspirin might have effects on multiple tumor
      suppressors, such as TP53, PTEN, and RB1 and that TP53 might play a central role
      in aspirin-associated genes. Discussion: The results not only suggest that
      aspirin might have anti-tumor actions against multiple cancers but could also
      provide new directions for further research on aspirin using a bioinformatics
      analysis approach.

PMID- 30280038
TI  - Distribution, habitat associations, and conservation status updates for the
      pilose crayfish Pacifastacus gambelii (Girard, 1852) and Snake River pilose
      crayfish Pacifastacus connectens (Faxon, 1914) of the western United States.
AB  - Our study evaluates the distribution, habitat associations, and current
      conservation status of the Snake River pilose crayfish Pacifastacus connectens
      (Faxon, 1914) and pilose crayfish Pacifastacus gambelii (Girard, 1852), two
      little-studied and data-deficient species endemic to the western United States.
      We first developed a species distribution model (SDM) for the pilose crayfishes
      based on their historical occurrence records using boosted regression trees and
      freshwater GIS data layers. We then sampled 163 sites in the summers of 2016 and
      2017 within the distribution of these crayfishes, including 50 where these
      species were observed historically. We next compared our field results to modeled
      predictions of suitable habitat from the SDM. Our SDM predicted 73 sites (45%) we
      sampled as suitable for the pilose crayfishes, with a moderate AUC value of
      0.824. The pilose crayfishes were generally predicted to occur in larger streams
      and rivers with less extreme upstream temperature and precipitation seasonality.
      We found the pilose crayfishes at only 20 (12%) of the 163 total sites we
      sampled, 14 (20%) of the 73 sites predicted as suitable for them by our SDM, and
      12 (24%) of 50 historical sites that we sampled. We found the invasive virile
      crayfish Faxonius virilis (Hagen, 1870) at 22 sites total and 12 (24%) historical
      sites for the pilose crayfishes, and we found the "native invader" signal
      crayfish Pacifastacus leniusculus (Dana, 1852) at 29 sites total and 6 (12%)
      historical sites for the pilose crayfishes. We subsequently used a single
      classification tree to identify factors associated with our high rate of false
      positives for contemporary pilose crayfish distributions relative to our SDM.
      This classification tree identified the presence of invasive crayfishes,
      impairment of the benthic community, and sampling method as some of the factors
      differentiating false positives relative to true positives for the pilose
      crayfishes. Our study identified the historical distribution and habitat
      associations for P. connectens and P. gambelii using an SDM and contrasted this
      prediction to results of contemporary field sampling. We found that the pilose
      crayfishes have seemingly experienced substantial range declines, attributable to
      apparent displacement by invasive crayfishes and impairment or change to stream
      communities and habitat. We recommend increased conservation and management
      attention to P. connectens and P. gambelii in response to these findings.

PMID- 30280039
TI  - Growth and feeding of deep-sea coral Lophelia pertusa from the California margin
      under simulated ocean acidification conditions.
AB  - The global decrease in seawater pH known as ocean acidification has important
      ecological consequences and is an imminent threat for numerous marine organisms.
      Even though the deep sea is generally considered to be a stable environment, it
      can be dynamic and vulnerable to anthropogenic disturbances including increasing
      temperature, deoxygenation, ocean acidification and pollution. Lophelia pertusa
      is among the better-studied cold-water corals but was only recently documented
      along the US West Coast, growing in acidified conditions. In the present study,
      coral fragments were collected at ~300 m depth along the southern California
      margin and kept in recirculating tanks simulating conditions normally found in
      the natural environment for this species. At the collection site, waters
      exhibited persistently low pH and aragonite saturation states (Omegaarag) with
      average values for pH of 7.66 +/- 0.01 and Omegaarag of 0.81 +/- 0.07. In the
      laboratory, fragments were grown for three weeks in "favorable" pH/Omegaarag of
      7.9/1.47 (aragonite saturated) and "unfavorable" pH/Omegaarag of 7.6/0.84
      (aragonite undersaturated) conditions. There was a highly significant treatment
      effect (P < 0.001) with an average% net calcification for favorable conditions of
      0.023 +/- 0.009% d-1 and net dissolution of -0.010 +/- 0.014% d-1 for unfavorable
      conditions. We did not find any treatment effect on feeding rates, which suggests
      that corals did not depress feeding in low pH/ Omegaarag in an attempt to
      conserve energy. However, these results suggest that the suboptimal conditions
      for L. pertusa from the California margin could potentially threaten the
      persistence of this cold-water coral with negative consequences for the future
      stability of this already fragile ecosystem.

PMID- 30280040
TI  - Biosorption potential of natural, pyrolysed and acid-assisted pyrolysed sugarcane
      bagasse for the removal of lead from contaminated water.
AB  - Lead (Pb) is a ubiquitous pollutant which poses serious threats to plants,
      animals and humans once entered into the food chain via contaminated industrial
      effluents on their discharge into the surface of water bodies and/or geological
      materials. This study aimed to examine and compare the biosorption potential of
      natural sugarcane bagasse (NB), pyrolysed sugarcane bagasse (PB) and acid
      assisted pyrolysed sugarcane bagasse (APB) for the removal of Pb from
      contaminated water. To explore this objective, a series of batch experiments were
      conducted at various adsorbent mass (0.25, 0.5, 0.75, 1.0 g per 100 ml
      contaminated water), initial Pb concentration (7, 15, 30, 60 and 120 ppm), and
      contact time (7, 15, 30, 60 and 120 min). Results revealed that all the tested
      bio-sorbents have potential to adsorb and remove Pb ions from the contaminated
      water. In this regard, APB proved more effective since it removed 98% of Pb from
      aqueous solution at initial Pb concentration of 7 ppm and mass of 0.25 g per 100
      ml of aqueous solution. The respective values in case of NB and PB were 90 and
      95%. For a given adsorbent type, Pb adsorption decreased by increasing the mass
      from 0.25 to 1.0 g per 100 ml of aqueous solution. However, the greatest Pb
      removal occurred at adsorbent mass of 1.0 g per 100 ml of aqueous solution.
      Initial Pb concentration had a great impact on Pb adsorption and removal by
      adsorbent. The former increased and the latter decreased with the increase in
      initial Pb concentration from seven to 120 ppm. At seven ppm Pb concentration,
      maximum Pb removal took place irrespective to the adsorbent type. Out of the
      total Pb adsorption and removal, maximum contribution occurred within 15 min of
      contact time between the adsorbate and adsorbent, which slightly increased till
      30 min, thereafter, it reached to equilibrium. Application of equilibrium
      isotherm models revealed that our results were better fitted with Freundlich
      adsorption isotherm model. Overall, and for the reasons detailed above, it is
      concluded that sugarcane bagasse has capabilities to adsorb and remove Pb ions
      from contaminated water. Its bio-sorption potential was considerably increased
      after pyrolysis and acid treatment.

PMID- 30280041
TI  - Population history of deep-sea vent and seep Provanna snails (Mollusca:
      Abyssochrysoidea) in the northwestern Pacific.
AB  - Background: Gastropods of the genus Provanna are abundant and widely distributed
      in deep-sea chemosynthetic environments with seven extant species described in
      the northwestern Pacific. Methods: We investigated the population history and
      connectivity of five Provanna species in the northwestern Pacific through
      population genetic analyses using partial sequences of the cytochrome c oxidase
      subunit I gene. Results: We found that P. subglabra, the most abundant and
      genetically diverse species, is genetically segregated by depth. Among the five
      species, the three comparatively shallower species (P. lucida, P. kuroshimensis,
      P. glabra) had a more constant demographic history compared to the deeper species
      (P. subglabra, P.  clathrata). Discussion: Environmental differences, especially
      depth, appears to have a role in the segregation of Provanna snails. The
      population of P. clathrata in the Irabu Knoll appears to have expanded after P.
      subglabra population. The remaining three species, P. lucida, P. kuroshimensis,
      and P. glabra, are only known from a single site each, all of which were
      shallower than 1,000 m. These data indicate that Provanna gastropods are
      vertically segregated, and that their population characteristics likely depend on
      hydrothermal activities.

PMID- 30280042
TI  - Size dimorphism and sexual segregation in pheasants: tests of three competing
      hypotheses.
AB  - Fine scale sexual segregation outside of the mating season is common in sexually
      dimorphic and polygamous species, particularly in ungulates. A number of
      hypotheses predict sexual segregation but these are often contradictory with no
      agreement as to a common cause, perhaps because they are species specific. We
      explicitly tested three of these hypotheses which are commonly linked by a
      dependence on sexual dimorphism for animals which exhibit fine-scale sexual
      segregation; the Predation Risk Hypothesis, the Forage Selection Hypothesis, and
      the Activity Budget Hypothesis, in a single system the pheasant, Phasianus
      colchicus; a large, sedentary bird that is predominantly terrestrial and
      therefore analogous to ungulates rather than many avian species which sexually
      segregate. Over four years we reared 2,400 individually tagged pheasants from one
      day old and after a period of 8-10 weeks we released them into the wild. We then
      followed the birds for 7 months, during the period that they sexually segregate,
      determined their fate and collected behavioural and morphological measures
      pertinent to the hypotheses. Pheasants are sexually dimorphic during the entire
      period that they sexually segregate in the wild; males are larger than females in
      both body size and gut measurements. However, this did not influence predation
      risk and predation rates (as predicted by the Predation Risk Hypothesis), diet
      choice (as predicted by the Forage Selection Hypothesis), or the amount of time
      spent foraging, resting or walking (as predicted by the Activity Budget
      Hypothesis). We conclude that adult sexual size dimorphism is not responsible for
      sexual segregation in the pheasant in the wild. Instead, we consider that
      segregation may be mediated by other, perhaps social, factors. We highlight the
      importance of studies on a wide range of taxa to help further the knowledge of
      sexual segregation.

PMID- 30280043
TI  - Distinguishing between enduring and dynamic concussion symptoms: applying
      Generalisability Theory to the Rivermead Post Concussion Symptoms Questionnaire
      (RPQ).
AB  - Background: The Rivermead Post Concussion Symptoms Questionnaire (RPQ) is a
      widely-used, 16-item measure of concussion symptoms yet its ability to assess
      change in the symptom experience over time has come under criticism. We applied
      Generalisability theory to differentiate between dynamic and enduring aspects of
      post-concussion symptoms and to examine sources of measurement error in the RPQ.
      Materials and Methods: Generalisability theory was applied using the longitudinal
      design with persons as the object of measurement. Patients with a traumatic brain
      injury (n = 145; aged >=16 years) were assessed at three time occasions (1, 6 and
      12 months post-injury) using the RPQ. Results: The RPQ showed overall strong
      generalisability of scores (G = .98) across persons and occasions with a minor
      proportion of variance attributed to the dynamic aspect of symptoms reflected by
      interaction between person and occasion. Items measuring concentration, fatigue,
      restlessness and irritability reflected more dynamic patterns compared to more
      enduring patterns of sensitivity to noise, impatience, nausea and sleep
      disturbance. Conclusion: The RPQ demonstrated strong reliability in assessing
      enduring post-concussion symptoms but its ability to assess dynamic symptoms is
      limited. Clinicians should exercise caution in use of the RPQ to track dynamic
      symptom change over time. Further investigation is necessary to enhance the RPQ's
      ability to assess dynamic symptoms and to address measurement error associated
      with individual items.

PMID- 30280044
TI  - In silico study of medical decision-making for rare diseases: heterogeneity of
      decision-makers in a population improves overall benefit.
AB  - Background: Medical decision-making is difficult when information is limited due
      to its rareness. For example, there are two treatment options for patients
      affected by a rare disease with high lethality. The information about both
      treatment effects is unavailable or very limited. Patients are inclined to accept
      one of the interventions rather than waiting for death, but they are reluctant to
      be assigned the inferior one. While a single patient selects one treatment that
      seems better based on the limited information, he or she loses the chance to
      select the other treatment, which may be the better option. This is the so-called
      dilemma between exploitation (enjoying the benefits of using current knowledge)
      and exploration (taking the risk to obtain new knowledge). In clinical settings,
      the statistical advice for individual patients seems to be the maximum expected
      success rate or something equivalent and patients' selections tend to be
      homogeneous, which does not solve the dilemma. In this study, our aim is to
      investigate the effects of the heterogeneity of decision-makers in the decision
      process. Methods: Here, we proposed a decision strategy that introduced the
      heterogeneity of decision-makers by considering patients' self-decisions where
      the patients' heterogeneous attitudes towards the treatment are integrated into
      the probabilistic utility function based on the Beta Bayesian posterior. Based on
      the context of two-armed bandit treatment options with limited information, we
      compared the overall success rate of treatment between our heterogeneous decision
      strategy and a homogeneous decision strategy that is defined to select the
      treatment with the largest posterior mean. Results: The heterogeneity of decision
      makers in a population improved the overall benefit of treatment under some
      conditions. Discussion: In clinical settings, there exists heterogeneity of
      decision-making among patients. Our study investigated a targeting strategy by
      respecting the self-decision of all individuals and found that the heterogeneity
      of decision-making can improve the overall benefit under some conditions. In
      addition, this outperformance may suggest that heterogeneity of decision-making
      is of importance to human beings. Besides the ethical merit, our findings provide
      meaningful ideas for better strategies towards decision-making dilemmas in
      clinical settings for rare diseases or cases where only limited information is
      available. Furthermore, it is suggested to investigate the effects of
      heterogeneity of decision-making in other fashions, such as genetic heterogeneity
      and phenotypic heterogeneity.

PMID- 30280045
TI  - Cellular production of a counterfeit viral protein confers immunity to infection
      by a related virus.
AB  - DNA copies of many non-retroviral RNA virus genes or portions thereof (NIRVs) are
      present in the nuclear genomes of many eukaryotes. These have often been
      preserved for millions of years of evolution, suggesting that they play an
      important cellular function. One possible function is resistance to infection by
      related viruses. In some cases, this appears to occur through the piRNA system,
      but in others by way of counterfeit viral proteins encoded by NIRVs. In the
      fungi, NIRVs may be as long as 1,400 uninterrupted codons. In one such case in
      the yeast Debaryomyces hansenii, one of these genes provides immunity to a
      related virus by virtue of expression of a counterfeit viral capsid protein,
      which interferes with assembly of viral capsids by negative complementation. The
      widespread occurrence of non-retroviral RNA virus genes in eukaryotes may reflect
      an underappreciated method of host resistance to infection. This work
      demonstrates for the first time that an endogenous host protein encoded by a gene
      that has been naturally acquired from a virus and fixed in a eukaryote can
      interfere with the replication of a related virus and do so by negative
      complementation.

PMID- 30280046
TI  - Investigating the relationship between intergroup physical contact and attitudes
      towards foreigners: the mediating role of quality of intergroup contact.
AB  - Recent research has shown that a brief, casual touch administered by an outgroup
      member reduces prejudice towards the group to which the toucher belongs. In this
      study, we take the research on physical contact and prejudice a step further by
      addressing the relation between individuals' amount of Experienced Intergroup
      Physical Contact (EIPC), across distinct contexts and involving different body
      parts, and attitudes towards foreign people. Specifically, we hypothesized that
      the amount of EIPC would be positively associated with both quantity and quality
      of intergroup contact, but that only quality would mediate the relationship
      between the amount of EIPC and outgroup attitudes, quality being more directly
      linked to the evaluative component of outgroup attitudes. To attain this aim, we
      asked participants to self-report the amount of EIPC, the quantity and quality of
      their intergroup contact and their attitudes towards foreign people. Consistent
      with our hypothesis: (1) as EIPC increased, positive attitudes towards foreign
      people increased; (2) higher levels of EIPC were associated with better quality
      and higher quantity of intergroup contact; (3) only quality of intergroup contact
      mediated the relationship between the amount of EIPC and attitudes towards
      foreign people. Results were discussed in relation to research on intergroup
      contact and physical contact.

PMID- 30280047
TI  - Meta-analysis of northeast Atlantic marine taxa shows contrasting phylogeographic
      patterns following post-LGM expansions.
AB  - Background: Comparative phylogeography enables the study of historical and
      evolutionary processes that have contributed to shaping patterns of contemporary
      genetic diversity across co-distributed species. In this study, we explored
      genetic structure and historical demography in a range of coastal marine species
      across the northeast Atlantic to assess whether there are commonalities in
      phylogeographic patterns across taxa and to evaluate whether the timings of
      population expansions were linked to the Last Glacial Maximum (LGM). Methods: A
      literature search was conducted using Web of Science. Search terms were chosen to
      maximise the inclusion of articles reporting on population structure and
      phylogeography from the northeast Atlantic; titles and abstracts were screened to
      identify suitable articles within the scope of this study. Given the proven
      utility of mtDNA in comparative phylogeography and the availability of these data
      in the public domain, a meta-analysis was conducted using published mtDNA gene
      sequences. A standardised methodology was implemented to ensure that the
      genealogy and demographic history of all mtDNA datasets were reanalysed in a
      consistent and directly comparable manner. Results: Mitochondrial DNA datasets
      were built for 21 species. The meta-analysis revealed significant population
      differentiation in 16 species and four main types of haplotype network were
      found, with haplotypes in some species unique to specific geographical locations.
      A signal of rapid expansion was detected in 16 species, whereas five species
      showed evidence of a stable population size. Corrected mutation rates indicated
      that the majority of expansions were estimated to have occurred after the
      earliest estimate for the LGM (~26.5 Kyr), while few expansions were estimated to
      have pre-dated the LGM. Conclusion: This study suggests that post-LGM expansion
      appeared to be common in a range of marine taxa, supporting the concept of rapid
      expansions after the LGM as the ice sheets started to retreat. However, despite
      the commonality of expansion patterns in many of these taxa, phylogeographic
      patterns appear to differ in the species included in this study. This suggests
      that species-specific evolutionary processes, as well as historical events, have
      likely influenced the distribution of genetic diversity of marine taxa in the
      northeast Atlantic.

PMID- 30280048
TI  - Functions of Candida albicans cell wall glycosidases Dfg5p and Dcw1p in biofilm
      formation and HOG MAPK pathway.
AB  - Background: Candida albicans is a commensal fungus that inhabits the oral mucosal
      surface and causes oral and systemic candidiasis. Oral candidiasis most commonly
      occurs in patients with AIDS, denture wearers and newborn children. Systemic
      candidiasis occurs mainly in immunocompromised patients and patients admitted to
      hospitals for prolonged periods. C. albicans homologous genes, DFG5 and DCW1,
      encode for two closely related cell wall proteins with putative
      glycosyltransferase enzyme activity and C-terminal GPI-anchors. Past studies have
      shown that individual DFG5 and DCW1 mutations are viable but simultaneous
      deletion of DFG5 and DCW1 in C. albicans results in lethality. However, the exact
      functions of these cell wall based enzymes, which represent potential drug
      targets, are not understood. Methods: C. albicans DFG5/DCW1 heterologous and
      conditional double mutant strains were assessed for growth and biofilm formation
      in comparison to wild type and parental strains. Cell wall and heat stress
      susceptibility of the mutant and control strains were assessed using agar
      spotting assays. Growth was assessed under normal and osmotic stress conditions
      along with light microscopy imaging. Biofilm dry weight and microscopic imaging
      analysis of biofilms was performed. Hypha formation in response to serum was
      analyzed using light microscopy imaging. Western blot analysis of mutant strains
      and control strains was performed to assess Hog1 basal levels and phosphorylation
      status. Results: Analysis of the heterologous mutants indicated that Dfg5p is
      more important for growth while Dcw1p appeared to play a role in cell wall
      integrity response. The conditional double mutant was observed to be less
      resistant to cell wall stress. However, growth of the mutants was similar under
      control and osmotic stress conditions. The mutants were also able to grow similar
      to wild type under heat stress. Biofilm formation was reduced in the mutants
      where DFG5 was deleted or suppressed. Hyphal morphogenesis was reduced although
      germ tube formation was observed in the biofilms of the mutant strains. Basal
      Hog1 protein levels were reduced or absent in the DFG5 and DCW1 mutants. However,
      osmotic stress was able to induce Hog1 protein levels comparable to wild type.
      Hog1 phosphorylation appeared to be slightly reduced although not significantly.
      In addition to biofilm assays, serum dose response imaging analysis indicated
      that hyphae formation in DFG5 and DCW1 mutants was defective. Conclusions: These
      data indicate that DFG5 and DCW1 are required for hyphal morphogenesis and
      biofilm formation in C. albicans. These functions may be regulated via basal Hog1
      MAPK which is required for transcriptional regulation of chitin synthesis.

PMID- 30280049
TI  - Modeled larval connectivity of a multi-species reef fish and invertebrate
      assemblage off the coast of Moloka'i, Hawai'i.
AB  - We use a novel individual-based model (IBM) to simulate larval dispersal around
      the island of Moloka'i in the Hawaiian Archipelago. Our model uses ocean current
      output from the Massachusetts Institute of Technology general circulation model
      (MITgcm) as well as biological data on four invertebrate and seven fish species
      of management relevance to produce connectivity maps among sites around the
      island of Moloka'i. These 11 species span the range of life history
      characteristics of Hawaiian coral reef species and show different spatial and
      temporal patterns of connectivity as a result. As expected, the longer the
      pelagic larval duration (PLD), the greater the proportion of larvae that disperse
      longer distances, but regardless of PLD (3-270 d) most successful dispersal
      occurs either over short distances within an island (<30 km) or to adjacent
      islands (50-125 km). Again, regardless of PLD, around the island of Moloka'i,
      connectivity tends to be greatest among sites along the same coastline and
      exchange between northward, southward, eastward and westward-facing shores is
      limited. Using a graph-theoretic approach to visualize the data, we highlight
      that the eastern side of the island tends to show the greatest out-degree and
      betweenness centrality, which indicate important larval sources and connectivity
      pathways for the rest of the island. The marine protected area surrounding
      Kalaupapa National Historical Park emerges as a potential source for between
      island larval connections, and the west coast of the Park is one of the few
      regions on Moloka'i that acts as a net larval source across all species. Using
      this IBM and visualization approach reveals patterns of exchange between habitat
      regions and highlights critical larval sources and multi-generational pathways to
      indicate priority areas for marine resource managers.

PMID- 30280050
TI  - Sunset Yellow and Allura Red modulate Bcl2 and COX2 expression levels and confer
      oxidative stress-mediated renal and hepatic toxicity in male rats.
AB  - Studies on the adverse health effects caused by azo dyes are insufficient and
      quite contradictory. This work aims to investigate the possible toxic effect of
      two types of widely used food additives, Sunset Yellow and Allura Red, by
      assessing the physiological, histopathological and ultrastructural changes in the
      liver and kidney. Also, we investigated the genotoxic effect of both dyes on
      white blood cells. Thirty adult male albino rats were divided into three groups
      of 10 animals each: control (received water), Sunset Yellow-treated (2.5 mg/kg
      body weight) and Allura Red-treated (seven mg/kg body weight). The doses were
      orally applied for 4 weeks. Our results indicated an increase in the biochemical
      markers of hepatic and renal function (Aspartate aminotransferase, alanine
      aminotransferase, urea, uric acid and creatinine) in animals administered with
      the azo dyes. We also observed a noticeable increase in MDA and a marked decrease
      in total antioxidant levels in azo dye-treated animals compared to controls.
      Conversely, both dyes adversely affected the liver and kidney of albino rats and
      altered their histological and fine structure, with downregulation of Bcl2 and
      upregulation of COX2 expression. Our comet assay results showed a significant
      elevation in the fold change of tail moment in response to application of Sunset
      Yellow but not Allura Red. Collectively, we show that Sunset Yellow and Allura
      Red cause histopathological and physiological aberrations in the liver and kidney
      of male Wistar albino rats. Moreover, Sunset Yellow but not Allura Red induces a
      potential genotoxic effect.

PMID- 30280051
TI  - Influence of sports expertise level on attention in multiple object tracking.
AB  - Background: This study aimed to investigate whether performance in a multiple
      object tracking (MOT) task could be improved incrementally with sports expertise,
      and whether differences between experienced and less experienced athletes, or non
      athletes, were modulated by load. Methods: We asked 22 elite and 20 intermediate
      basketball players, and 23 non-athletes, to perform an MOT task under three
      attentional load conditions (two, three, and four targets). Accuracies were
      analyzed to examine whether different levels of sports expertise influence MOT
      task performance. Results: The elite athletes displayed better tracking
      performance compared with the intermediate or non-athletes when tracking three or
      four targets. However, no significant difference was found between the
      intermediate athletes and the non-athletes. Further, no differences were observed
      among the three groups when tracking two targets. Discussion: The results suggest
      that the effects of expertise in team ball sports could transfer to a non-sports
      specific attention task. These transfer effects to general cognitive functions
      occur only in elite athletes with extensive training under higher attentional
      load.

PMID- 30280052
TI  - Hepatocellular Carcinoma Occurrence and Recurrence in Hepatitis C-infected
      Patients Treated with Direct-acting Antivirals.
AB  - Introduction Multiple studies have shown the efficacy of the new direct-acting
      antivirals (DAAs) with a cure rate of over 90% in hepatitis C virus (HCV)
      infected patients. Some recently published studies have suggested an increased
      incidence of de novo and recurrent hepatocellular carcinoma (HCC) in cirrhotic
      patients in sustained virological response (SVR) after completing therapy. A
      possible mechanism is the breakdown of immune surveillance after starting DAAs.
      We report a retrospective analysis on a population of chronic HCV infected
      patients, with and without a prior history of HCC, who developed HCC after
      receiving DAAs in the hope of adding to existing literature and in pursuit of
      greater clarity into this emerging concern with DAAs. Methods We analyzed 497 HCV
      infected patients who were treated with DAAs, or a combination of DAA with
      interferon, from January 2014 to April 2017 at the Veterans Medical Center,
      Oklahoma City. Descriptive analysis, including the mean and standard deviation
      for different variables, was used. The cohort was divided into two groups:
      cirrhotic and non-cirrhotic. The analysis was run in the cirrhotic group between
      the subgroups who developed HCC and who did not. Results Data from a total of 233
      cirrhotic patients were analyzed. We further subdivided these patients into those
      who eventually were diagnosed with HCC (group 1) and those who were not (group
      2). These subgroups were comparable in regards to race, gender, baseline serum
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelets,
      sodium, HCV genotypes, and pretreatment viral load. All patients completed
      therapy. The rate of SVR was much lower in group 1 compared to group 2 (62.5% vs
      88.94%, p = 0.002), respectively. Model End-stage Liver Disease (MELD) score,
      Child-Turcotte-Pugh (CTP) score, and Fibrosis-4 (FIB-4) score were higher in the
      group that developed HCC. The average time period (weeks) from DAA therapy to HCC
      diagnosis was 48.2 weeks. The remaining 264 non-cirrhotic patients had no
      reported cases of HCC. Conclusion From a total of 497 treated HCV-infected
      patients, 233 (46.88 %) had cirrhosis, out of which 16 (6.86%) were reported to
      develop HCC during or after DAA therapy was initiated. The remaining 217 (93.1%)
      cirrhotic patients did not develop HCC. As per our comparison, achieving SVR in
      cirrhotic patients should not preclude HCC screening, and more studies are needed
      to assess the risk of HCC in patients who achieve SVR but have a high FIB-4
      score. In fact, patients who do not achieve SVR may be at a higher risk of
      eventually developing HCC and may be candidates for closer surveillance.

PMID- 30280054
TI  - Persistent Alopecia in a Breast Cancer Patient Following Taxane Chemotherapy and
      Adjuvant Endocrine Therapy: Case Report and Review of Post-treatment Hair Loss in
      Oncology Patients with Breast Cancer.
AB  - Taxane chemotherapy and adjuvant endocrine therapy are commonly used in breast
      cancer patients following surgery. We describe a 59-year-old woman with a triple
      positive invasive right breast cancer that was treated with surgery, radiation,
      chemotherapy, and adjuvant hormonal therapy. She subsequently developed scalp
      alopecia, with histopathological features of both androgenetic alopecia and
      alopecia areata; the hair loss did not resolve after completion of her
      chemotherapy. Significant clinical improvement was observed with topical
      minoxidil therapy. PubMed was searched for the following terms: alopecia, breast,
      cancer, chemotherapy, endocrine, hair, loss, minoxidil, permanent, and taxane.
      The papers containing these terms and their references were reviewed. Temporary
      hair loss is frequently observed following taxane chemotherapy; however, albeit
      uncommon, persistent or permanent alopecia may occur in women with breast cancer
      who have been treated with taxane chemotherapy and endocrine therapy. It may be
      reasonable to initiate therapy with topical minoxidil in breast cancer patients
      who develop alopecia after treatment with either taxane chemotherapy or endocrine
      therapy alone or both.

PMID- 30280053
TI  - Impact of Neoadjuvant Chemotherapy on the Administration of Concurrent
      Chemoradiation for Locally Advanced Nasopharyngeal Carcinoma.
AB  - Objectives The standard of care for locally advanced nasopharyngeal carcinoma
      (NPC) is concurrent cisplatin chemoradiotherapy. Neoadjuvant chemotherapy can be
      administered to downsize tumors before concurrent treatment to optimize radiation
      volumes. Our hypothesis was that the use of cisplatin in the neoadjuvant phase
      could limit the amount of cisplatin that patients could tolerate in the
      concurrent phase of treatment. Methods This is a retrospective analysis of
      Canadian NPC patients who received neoadjuvant chemotherapy with the intention to
      downsize locally advanced tumors prior to concurrent cisplatin plus radiation.
      Baseline demographic and treatment data were obtained from institutional
      databases and chart review; all data were analyzed with SPSS (SPSS Inc. Released
      2005. SPSS for Windows, Version 14.0. Chicago: SPSS Inc.) Overall survival (OS),
      disease-specific survival (DSS), and local/regional relapse-free survival (LRRFS)
      were analyzed using Kaplan-Meier survival functions. Univariate and multivariate
      models were used to determine factors associated with the total dose of
      concurrent chemotherapy. Results Forty-six patients were identified as receiving
      neoadjuvant chemotherapy before concurrent chemoradiotherapy. In the univariate
      and multivariate analyses of patients who received concurrent chemotherapy,
      receiving over 200 mg/m2 concurrent cisplatin with radiation was associated with
      a higher neoadjuvant dose of chemotherapy received. The median follow-up time was
      2.6 years (range, 0.17 years to 10.6 years). At three years, the OS was 83%, DSS
      was 86%, and LRRFS was 74%. Conclusions NPC patients have been treated with
      neoadjuvant chemotherapy at this center with favorable outcomes. Most patients
      could tolerate concurrent chemotherapy after radiotherapy. Receiving higher doses
      of concurrent chemotherapy was associated with also having higher doses of
      neoadjuvant cisplatin. This suggests that neoadjuvant cisplatin is not a limiting
      factor in the delivery of full-dose concurrent chemotherapy.

PMID- 30280055
TI  - Persistent Psychosis due to Single Dose of Ecstasy.
AB  - Ecstasy, a popular drug among the younger generation, the primary psychoactive
      component of which is 3,4-Methylenedioxymethamphetamine (MDMA), is rarely known
      to have acute psychiatric effects and when it does, it is usually short term. We
      describe a patient who presented to the emergency room in a psychotic state after
      using ecstasy recreationally. Given his aggressive behavior in the community and
      risk for self-harm, he was emergently hospitalized to ensure safety. He developed
      persistent psychotic symptoms (delusions) after one dose of recreational MDMA and
      the team had the opportunity to observe, monitor, and treat his psychosis. This
      case along with few other documented cases highlights the gaps in research about
      the chronic, persistent effects and long-term consequences of MDMA. It also
      suggests that neuropsychiatric symptoms may not be readily reversible after
      cessation of use. There is an emphasis on the need for physicians to inquire
      about MDMA use and include it in toxicology screenings and as a potential
      differential diagnosis.

PMID- 30280056
TI  - Comparative Evaluation of the Remineralization Potential of Monofluorophosphate,
      Casein Phosphopeptide-Amorphous Calcium Phosphate and Calcium Sodium
      Phosphosilicate on Demineralized Enamel Lesions: An In Vitro Study.
AB  - AIM: The aim of the study is to compare the remineralization potential of
      monofluorophosphate, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP),
      and calcium sodium phosphosilicate on demineralized enamel lesions. MATERIALS AND
      METHODS: Enamel sections from 30 sound human premolar crowns were prepared and
      sectioned into quadrants. Early enamel lesions were created in each sample by
      immersion in a demineralizing solution for 72 hours. Of the four sections, the
      first quadrant (A) was not given any surface treatment, the second quadrant (B)
      was treated with monofluorophosphate dentifrice, the third (C) was treated with
      casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), and the fourth (D)
      was treated with calcium sodium phosphosilicate while being subjected to a five
      day pH cycling protocol. The sections were further cross-sectioned to expose the
      lesion depth and were then viewed under the confocal laser scanning microscope
      after staining with 0.1 mM rhodamine B dye for 24 hours. The two parameters
      evaluated were the cross-sectional demineralized lesion area and total
      fluorescence. RESULTS: Amongst the dentifrices tested, the lowest values for
      lesion area and total fluorescence were recorded by calcium sodium
      phosphosilicate (3874.1 u2 and 107282.6, respectively), followed by casein
      phosphopeptide-amorphous calcium phosphate (5776.6 u2 and 129470.8) and then by
      monofluorophosphate dentifrice (7371.2 u2 and 233765.9) in increasing order. The
      highest values for lesion area and total fluorescence were recorded by the no
      treatment group (16449.2 u2 and 759743.1). One-way analysis of variance (ANOVA)
      showed significant variations (p<0.01) between the groups and Scheffe multiple
      comparisons confirmed the significance (p<0.01) of intergroup variations.
      CONCLUSION: The results of this study suggest that, among the three agents
      tested, calcium sodium phosphosilicate is the most effective remineralizing agent
      followed by casein phosphopeptide-amorphous calcium phosphate.
      Monofluorophosphate is the least effective remineralizing agent when tested under
      the conditions mentioned in this study.

PMID- 30280057
TI  - Antidromic Atrioventricular Reentrant Tachycardia Dependent on a Unidirectional
      Left Anterior Accessory Pathway Mimicking Peri-mitral Ventricular Tachycardia:
      Successful Ablation via a Transseptal Approach.
AB  - Antidromic atrioventricular reentrant tachycardia (aAVRT) is rare compared to
      orthodromic atrioventricular reentrant tachycardia (oAVRT). An aAVRT that is
      dependent on a unidirectional, decremental accessory pathway (AP) is even rarer.
      Idiopathic ventricular tachycardias (iVT) that have benign prognoses and respond
      well to medical therapy can be confused with aAVRTs dependent on APs having
      ventricular insertion sites close to the iVT focus and have a real risk of sudden
      death. The preferred approach of ablation for such tachycardias with anterograde
      conduction only is a retrograde aortic approach, which facilitates the mapping of
      the earliest ventricular activation during atrial pacing or tachycardia from the
      ventricular side. This, however, necessitates access to the arterial system with
      accompanying complications. We describe herein the case of a wide complex
      tachycardia, which was treated initially as VT with intravenous lidocaine. The
      baseline electrocardiogram (ECG) did not show preexcitation. An electrophysiology
      study (EPS) revealed a left anterior AP that conducted anterograde only. AVRT was
      easily inducible at a cycle length of 290 ms. Successful ablation was undertaken
      via the transseptal approach without recurrence.

PMID- 30280059
TI  - Clinical Context Generation for Imaging: A Design Thinking-based Analysis of a
      Pilot Project.
AB  - Design Thinking is a method for the practical, creative resolution of problems
      using the strategies used during the process of designing. It is increasingly
      being used in Medical enterprise to develop a solution-based approach to identify
      ambiguous problems and create alternative paths to the solution. We faced several
      challenges in the development of a clinical context generation tool and in this
      article, we retrospectively assess the usefulness of a Design Thinking approach
      had it been applied to a project related to Medical Imaging-related clinical
      context generation.

PMID- 30280058
TI  - Vitamin C: A Preventative, Therapeutic Agent Against Helicobacter pylori.
AB  - The treatment of Helicobacter pylori (H. pylori) induced infections using
      antibiotic therapies is clinically well accepted; however, using a noninvasive
      approach with the implementation of therapeutic agents such as vitamin C is not
      well investigated. Vitamin C has certain characteristics, which allow for it to
      be considered as a potential treatment option for patients with H. pylori
      infections. Vitamin C's hostility and mechanism of action towards H. pylori
      infection in peptic ulcer disease can be classified into two categories: as a
      preventative agent and alternatively as a therapeutic agent. Preventatively
      vitamin C acts as a biological antioxidant as well as an immune boosting agent,
      while therapeutically it acts as an inhibitor of urease, a potential collagen
      synthesizing agent, and a stimulant in prostaglandin synthesis. As a result, the
      dosage of vitamin C should be highly regulated. Furthermore, numerous studies
      have shown that vitamin C supplementation if taken with antibiotics can increase
      the efficiency of the treatment leading to an increased possibility of
      eradication of H. pylori in infected individuals. This paper will investigate the
      recent studies that show different mechanisms through which vitamin C can be used
      as a preventative or a therapeutic agent for the treatment of H. pylori related
      infections.

PMID- 30280060
TI  - An Overview of Our Current Understanding of Diabetic Macular Ischemia (DMI).
AB  - Diabetic macular ischemia (DMI) is a troublesome complication of diabetes
      mellitus. The pathogenesis, progression, consequences, and treatment options for
      this disease are still poorly understood. However, it is believed that this
      complication is associated with several risk factors like poor glycemic control
      and high blood pressure. Two factors have been identified in the pathogenesis of
      the disease that play pivotal roles in disease development and progression. One
      of these factors includes extensive damage to the microvasculature of the retina.
      This includes narrowing of the vascular lumen and extensive damage to the
      endothelial cells, pericytes and the extracellular matrix. The second factor
      includes extensive damage to the neurosensory layer of the retina. DMI is always
      associated with other complications of diabetic retinopathy like retinal edema,
      so it is very difficult to find an isolated case of DMI. Moreover, the condition
      is also very rare making it very difficult to study and diagnose. However, a
      number of diagnostic tests like optical coherence tomography (OCT), fluorescence
      angiography (FA), and perimetry can be used as tools for the early detection of
      DMI. Since this disease damages the retina, loss of vision is an inevitable
      consequence that can progressively worsen over time. Also, DMI has been
      implicated as a risk factor for retinal edema and progressive diabetic
      retinopathy. Until now, no defined treatment protocol has been devised. The only
      available treatments focus on the management of risk factors (hyperglycemia and
      hypertension). Still, many aspects of DMI remain poorly studied and understood.
      This review paper aims to add to our current understanding of diabetic macular
      ischemia (DMI).

PMID- 30280061
TI  - Use of MitraClip for Postmyocardial Infarction Mitral Regurgitation Secondary to
      Papillary Muscle Dysfunction.
AB  - Papillary muscle rupture after acute myocardial infarction (AMI) is a dreadful
      complication and it is associated with five percent of deaths following AMI.
      Surgery is the recommended treatment of choice; however, it is usually deferred
      due to the high risk of mortality. MitraClip implantation using a transcatheter
      approach is an alternative option for patients with severe mitral regurgitation
      (MR) following AMI or those with high operative risk. We report a case of a 68
      year-old male patient who developed severe MR secondary to AMI and underwent
      successful mitral valve repair using the MitraClip device.

PMID- 30280063
TI  - How To Be a Leader: A Course for Residents.
AB  - BACKGROUND: Physicians are required to assume a leadership role as part of their
      career. For most, this is not an innate characteristic and must be developed
      throughout their medical training. There are few residency courses designed to
      assist in the enhancement of these leadership skills. We created and implemented
      a novel course on leadership, utilizing weekly presentations designed to
      stimulate discussions and improve the leadership qualities of trainees. METHODS:
      Senior residents provided leadership lectures stimulated by assigned readings
      from the book "The Founding Fathers on Leadership." The traits and
      characteristics demonstrated throughout course readings and discussions were
      subsequently incorporated into everyday resident activities. Baseline and post
      course survey responses were evaluated to assess changes in leadership qualities.
      RESULTS: Seven senior (postgraduate year (PGY) 3-5) participated as course
      leaders. All seven filled out pre- and post-course surveys. Seventeen junior
      residents (PGY 1-2) were involved as audience members. Significant pre- and post
      course differences were noted in the following areas: feelings of increased
      encouragement of personal development (4.86 vs. 5.43, p=0.03); increased team
      participation in decision-making (4.00 vs. 4.57, p=0.03); increased ease of
      obtaining answers to difficult questions (4.57 vs. 5.23, p=0.047); increased team
      member work (4.86 vs. 5.71, p=0.047), and a sense of leading a more balanced life
      (3.86 vs. 4.43, p=0.03). CONCLUSION: The initiation of a novel leadership course
      for senior surgical residents led to an enjoyable experience, resulting in
      enhanced leadership skills for all participants. We believe this process resulted
      in a more cohesive, efficient, communicative, and supportive residency program.

PMID- 30280062
TI  - Endogenous Endophthalmitis: A Five-year Review of Cases at the Raja Perempuan
      Zainab II Hospital, Kelantan, Malaysia.
AB  - Background Endogenous endophthalmitis (EE) is a type of intraocular inflammation
      secondary to hematogenous spread from a distant infective source within the body
      and usually occurs in immunocompromised patients. Objectives The aim of this
      study was to profile the patient characteristics, sources of infection, microbial
      profiles, and visual outcomes of patients with EE in Raja Perempuan Zainab II
      Hospital in Kelantan, Malaysia. Materials and methods Data from 18 eyes of 17
      patients diagnosed with EE and admitted to the eye ward of Raja Perempuan Zainab
      II Hospital from January 2012 to December 2016 were retrospectively reviewed.
      Factors analyzed included patient age, sources of infection, visual acuity,
      microbial profiles, and treatment outcomes. Results The mean age of the 17
      patients was 53.2 years. Twelve patients (70.6%) had EE of left eye, four (23.5%)
      had EE of right eye, and one (5.9%) had EE involving both the eyes. Sixteen
      patients (91.1%) had at least one predisposing condition, the most common of
      which was diabetes mellitus in 15 patients (88.2%). A source of infection was
      identified in 12 of the 17 patients, with urinary tract infection being the most
      common (five patients, 29.4%). Organisms were successfully isolated from 10
      (58.8%) patients, including seven (41.2%) with Gram-negative and three (17.6%)
      with Gram-positive organisms. All patients presented with a visual acuity worse
      than 6/60. Nine (52.9%) patients underwent vitrectomy, with only two of these
      patients achieving a final visual acuity better than 6/60. Eleven patients became
      nonperceptive to light, with four of them undergoing evisceration. Conclusions EE
      is a rare but often devastating ocular condition. Visual outcomes are often poor
      especially in patients infected with Gram-negative bacteria.

PMID- 30280064
TI  - A Rare Case of Melanotic Schwannoma: Utility of Susceptibility Weighted Sequences
      in Preoperative Imaging.
AB  - Intracranial schwannomas account for 8% of all intracranial tumors, out of which
      90% are acoustic schwannomas. Other rare varieties include trigeminal melanotic
      schwannomas that account for 0.2% of all intracranial tumors. Melanotic
      schwannomas are intracranial tumors that are heavily pigmented due to the
      presence of melanin. The most common origination of the tumor involves being
      confined to Meckel's cave, presenting with features of trigeminal neuralgia,
      neurasthenia, and numbness. We report a case of a 48-year-old male presenting
      with dysarthria, left-sided hemiparesis, dysphagia, and headache for the past six
      months. Magnetic resonance imaging (MRI) confirmed a mass in the right
      cerebellopontine (CP) angle, which extended into the middle cranial fossa. Our
      case is interesting because it is the fourth case reported worldwide.

PMID- 30280065
TI  - The Incisive Canal: A Comprehensive Review.
AB  - The incisive canal, also known as the nasopalatine canal, is an interosseous
      conduit through the anterior maxilla connecting the oral and nasal cavities.
      Within this canal lies the nasopalatine nerve and the vascular anastomosis
      between the greater palatine and sphenopalatine arteries. The embryology of the
      canal has led to interesting theories explaining its function. Efforts have been
      made to describe the morphometrics of the incisive canal by radiologic evaluation
      across sex and ethnicities. This paper aims to review the current literature on
      the embryology, anatomy, and clinical relevance of the incisive canal.

PMID- 30280066
TI  - Netherton Syndrome: A Case Report and Review of Literature.
AB  - Netherton syndrome (NS) is a rare autosomal recessive disorder characterized by a
      triad of congenital ichthyosiform erythroderma (CIE) or ichthyosis linearis
      circumflexa (ILC), hair shaft abnormalities, and atopic diathesis (elevated serum
      IgE ). We report a case of a two-year-old boy presented with intractable
      pruritus, scaling, dry skin and generalized eczematous lesions resistant to
      atopic dermatitis therapy. Netherton syndrome misdiagnosed as atopic dermatitis
      due to the presence of eczematous skin lesions and allergic problems. The family
      counseled about the diagnosis and need of genetic testing for confirmation, but
      they refused for genetic testing. The patient got treatment with topical
      corticosteroids and skin moisturizers. There is no cure or satisfactory treatment
      currently available for NS. Further understanding of the underlying
      pathophysiology of integumentary changes will lead to more effective treatment.
      Netherton syndrome should be in the differential diagnosis when characteristic
      skin manifestation of CIE or ILC, and elevated serum IgE present.

PMID- 30280067
TI  - Laboratory Evaluation of a Robotic Operative Microscope - Visualization Platform
      for Neurosurgery.
AB  - Background We assessed a new robotic visualization platform with novel user
      control features and compared its performance to the previous model of operative
      microscope. Methods In a neurosurgery research laboratory, we performed
      anatomical dissections and assessed robotic, exoscopic, endoscopic, fluorescence
      functionality. Usability and functionality were tested in the operating room over
      1 year. Results The robotic microscope showed higher sensitivity for fluorescein
      sodium, higher detail in non-fluorescent background, and recorded/presented
      pictures with color quality similar to observation through the oculars. PpIX
      visualization was comparable to the previous microscope. Near-infrared
      indocyanine green imaging 3-step replay allowed for more convenient accurate
      assessment of blood flow. Point lock and pivot point functions were used in
      dissections to create 3D virtual reality microsurgical anatomy demonstrations.
      Pivot point control was particularly useful in deep surgical corridors with
      dynamic retraction. 3D exoscopic function was successfully used in brain tumor
      and spine cases. Endoscopic assistance was used for around-the-corner views in
      minimally invasive approaches. We present illustrative cases highlighting utility
      and new ways to control the operative microscope. Conclusion Improvements of the
      robotic visualization platform include intraoperative fluorescence visualization
      using FNa, integrated micro-inspection tool, improved ocular imaging clarity, and
      exoscopic mode. New robotic movements positively assist the surgeon and provide
      improved ergonomics and a greater level of intraoperative comfort, with the
      potential to increase the viewing quality. New operational modes also allow
      significant impact for anatomy instruction. With the increasing number and
      complexity of functions, surgeons should receive additional training in order to
      avail themselves of the advantages of the numerous novel features.

PMID- 30280068
TI  - Successful Transplantation of Pediatric Kidneys Despite Vascular Injuries.
AB  - The gap between the kidney transplant recipient list and the number of organs
      available for transplantation continues to grow. Pediatric donors help fill a
      small and valuable portion of that gap. Normally these organs are transplanted en
      bloc by closing the proximal vascular caps and using the distal aorta and distal
      inferior vena cava (IVC) for inflow. They are however commonly injured during the
      donor operation making the standard operation for pediatric en-bloc
      transplantation not possible. This case report presents two cases in which
      injured small pediatric kidneys were transplanted successfully in adult patients.
      We are presenting two examples of common vascular injuries to small pediatric
      kidneys, one venous and one arterial. In both scenarios, the kidneys were
      transplanted using a modification to the standard technique. The two kidneys were
      separated and the technique of implantation was modified to allow safe
      transplantation. This way we were able to transplant both kidneys successfully
      and using a reproducible methodology. Both recipients were young adults. There
      were no surgical complications.

PMID- 30280069
TI  - Subcutaneous Fat Necrosis and Hypercalcemia After Therapeutic Hypothermia in
      Patients With Hypoxic-ischemic Encephalopathy: A Case Series.
AB  - Therapeutic hypothermia (TH) is provided to newborns with moderate to severe
      hypoxic-ischemic encephalopathy (HIE) to improve survival and long-term
      neurodevelopmental outcomes. Although the benefits certainly outweigh the risks
      associated with therapeutic hypothermia, it is important to be mindful of
      potential rare side effects in the background of asphyxia-related injury to
      various body organs. One of those side effects includes subcutaneous fat necrosis
      (SCFN) that can occur in term newborns after perinatal hypoxia-ischemia or other
      stressing factors such as systemic hypothermia. It is usually a self-limited
      condition, however, in some cases, it can lead to severe hypercalcemia. We report
      three such cases of SCFN in newborns with HIE treated with TH. Due to potential
      long-term complications, such as metastatic calcifications, caregivers should be
      informed about this potential complication prior to discharge from hospital so
      that they can help diagnose or continue to monitor cases of severe hypercalcemia.

PMID- 30280071
TI  - The Impact of the Hippocratic Oath in 2018: The Conflict of the Ideal of the
      Physician, the Knowledgeable Humanitarian, Versus the Corporate Medical
      Allegiance to Financial Models Contributes to Burnout.
AB  - The tradition in medical school includes taking the Hippocratic Oath usually at
      graduation. The purpose of this review is to examine what that oath has been,
      what forms it currently has, and the implications for physicians in today's
      healthcare environment. The changes in health economics affect physicians as they
      try to follow the oath's allegiance to the individual patient's needs. At times,
      this goal conflicts with the perspective of the financial world's controls of
      insurance companies and medical groups and institutions. This difference of the
      physicians' ethical perspectives from the business leaders regarding the
      philosophy of the value of the individual's health and life may be related to
      some aspect of physician burnout.

PMID- 30280070
TI  - Outcomes of Metastatic Brain Lesions Treated with Radioactive Cs-131 Seeds after
      Surgery: Experience from One Institution.
AB  - Introduction Brain metastases are common in patients with advanced systemic
      cancer and often recur despite treatment with surgical resection and
      radiotherapy. Whole brain radiation therapy (WBRT) and stereotactic radiosurgery
      (SRS) have significantly improved local control rates but are limited by
      complications including neurocognitive deficits and radiation necrosis. These
      risks can be higher in the re-irradiation setting. Brachytherapy may be an
      alternative method of additional targeted adjuvant radiotherapy with acceptable
      rates of toxicity. Methods A retrospective chart review of all patients
      undergoing resection for metastatic brain lesions and permanent low-dose rate Cs
      131 brachytherapy was performed for one institution over a 10-year period. All
      patients had previous radiation therapy already and, after surgery, were followed
      with imaging every three months. Patient demographics, disease characteristics,
      intracranial disease, peri- and post-operative complications, and outcomes were
      recorded. The primary outcome of interest was local tumor recurrence at the site
      of brachytherapy while secondary outcomes included distant disease progression
      (within the brain) and complications such as radiation necrosis. Results During
      the study period, nine cases of individual patients met inclusion criteria. The
      median preoperative lesion diameter was 3 cm (0.8-4.1). The median overall
      survival after surgery and brachytherapy was 10.3 months, after excluding two
      patients who were lost to follow-up. Six of nine patients had no local
      recurrence, while three patients had development or progression of distant
      lesions. No patients experienced acute or delayed complications. Conclusion Cs
      131 brachytherapy is a promising alternative method for controlling brain
      metastases after previous radiation interventions and surgical resection. In this
      case series, there were no incidences of local tumor recurrence or complications
      such as radiation necrosis.

PMID- 30280072
TI  - Extending the Concept of Vaccinology to the Control of Multidrug-resistant Sepsis
      in Neonates.
AB  - Standard infection control bundles have not been consistently effective in
      combating sepsis due to multidrug-resistant organisms (MDROs). Recent trials
      showing the beneficial effects of probiotics in controlling late-onset sepsis,
      the so-called "cross-contamination" or "cross-colonization" phenomenon that draws
      a parallel with the herd immunity concept in vaccinology. This editorial
      highlights the putative benefits of adapting the vaccinology-based concept using
      probiotic bacteria in our combat against MDROs.

PMID- 30280073
TI  - Natural History of Isolated Skull Fractures in Children.
AB  - Head injury is the most common cause of neurologic disability and mortality in
      children. We had hypothesized that in children with isolated skull fractures
      (SFs) and a normal neurological examination on presentation, the risk of
      neurosurgical intervention is very low. We retrospectively reviewed the medical
      records of all children aged six to sixteen years presenting to our Level 1
      trauma center with traumatic brain injuries between January 1, 2006 and December
      31, 2014. We also analyzed the National Trauma Data Bank (NTDB) research data set
      for the years 2012-2014 using the same metrics. During this study period, our
      center admitted 575 children with skull fractures, 197 of which were isolated (no
      associated intracranial lesions (ICLs)). Of the 197 patients with isolated SFs,
      155 had a normal neurological examination at presentation. In these patients,
      there were no fatalities and only three (1.9%) required surgery, all for the
      elevation of the depressed skull fracture. Analyzing the NTDB yielded similar
      results. In 5,194 children with isolated SFs and a normal neurological
      examination on presentation, there were no fatalities and 249 (4.8%) required
      neurosurgical intervention, almost all involving craniotomy/craniectomy and/or
      elevation of the SF segments. In conclusion, children with non-depressed isolated
      skull fractures and a normal Glasgow coma scale (GCS) at the time of initial
      presentation are at extremely low risk of death or needing neurosurgical
      intervention.

PMID- 30280074
TI  - Bacterial lactase genes diversity in intestinal mucosa of dysbacterial diarrhea
      mice treated with Qiweibaizhu powder.
AB  - The current research tried to investigate the effect of Qiweibaizhu powder
      (QWBZP) on intestinal mucosa bacterial lactase gene from dysbacterial diarrhea
      mice, as the good therapeutic mechanism of QWBZP on antibiotics-induced diarrhea.
      Dysbacterial diarrhea mice model was constructed by gastric perfusion with
      mixture of cephradine capsules and gentamicin sulfate (23.33 mL kg-1 day-1) for 5
      days. After the success of establishing diarrhea, the mice in treatment group
      were gavaged with QWBZP for 3 days. Intestinal mucosa in each group was
      collected, and diversity of bacterial lactase genes in intestinal mucosa of mice
      was carried out by Miseq metagenome sequencing. The results showed the Chao1,
      ACE, Simpson and Shannon indices in treatment group were lower than model group
      and were similar to control group. The same result was obtained from the
      operational taxonomic units (OTUs). There were 298, 435 and 254 OTUs in the
      control group, model group and treatment group, respectively. Principal component
      analysis (PCA) indicated that samples distribution in both normal and treatment
      groups were relatively intensive, distances among individuals were small, while
      opposite results were observed in model group. Moreover, antibiotics increased
      the diversity and abundance of bacterial lactase genes at phylum and genus
      levels. However, they decreased and were similar to control group after treating
      with QWBZP. Our results indicate that QWBZP has a positive effect on the recovery
      of bacterial lactase gene diversity to normal level. In addition, QWBZP increase
      the abundance of Lysobacter and Eukaryota.

PMID- 30280075
TI  - Disappearance of a thrombotic microangiopathy-like glomerular lesion in a patient
      with a placental site trophoblastic tumor after hysterectomy.
AB  - A 32-year-old woman presented with amenorrhea after a normal childbirth and
      subsequently developed nephrotic syndrome. Renal biopsy showed a thrombotic
      microangiopathy (TMA)-like glomerular lesion with deposits of immunoglobulins,
      complements, and fibrinogen. Increased serum levels of the beta subunit of human
      chorionic gonadotropin, abnormal uterine findings from imaging studies, and
      endometrial biopsy findings suggested gestational trophoblastic disease. She was
      diagnosed with a placental site trophoblastic tumor (PSTT) after hysterectomy
      and, following treatment, her proteinuria disappeared. Follow-up renal biopsy
      showed the disappearance of the TMA-like lesion. To our knowledge, this is the
      first case report of the pathological remission of renal disease associated with
      PSTT.

PMID- 30280076
TI  - A Comparison of Three Different Methods of Fixation in the Management of
      Thoracolumbar Fractures.
AB  - Background: Management of thoracolumbar fractures remains controversial in the
      literature. The primary aims of this study were to assess different levels of
      fixation with respect to radiological outcomes in terms of fracture reduction and
      future loss of correction. Methods: This is a single center, retrospective study.
      Fifty-five patients presenting with thoracolumbar fractures between January 2012
      and December 2015 were analyzed in the study. The levels of fixation were divided
      in 3 groups: 1 vertebra above and 1 below the fracture (1/1), 2 above and 2 below
      (2/2), and 2 above and 1 below (2/1). Results: The most common mechanism was high
      fall injury, and the most common vertebra L1. Burst fractures were the ones with
      the highest incidence. The 2/2 fixation achieved the best reduction of the
      fracture, but with no statistical significance. The correction is maintained
      better by the 2/2 fixation, but there is no statistical difference compared to
      the other fixations. Insertion of screws at the fracture level did not improve
      outcomes. Conclusion: The data of this study identified a trend toward better
      radiological outcomes for fracture reduction and maintenance of the correction in
      the 2/2 fixations. However, these results are not statistically significant.
      Future multicenter prospective clinical trials are needed in order to agree on
      the ideal management and method of fixation for thoracolumbar fractures.

PMID- 30280077
TI  - Anatomical Modifications during the Lateral Transpsoas Approach to the Lumbar
      Spine. The Impact of Vertebral Rotation.
AB  - Background: We investigated impact of vertebral axial rotation on neurovascular
      anatomy in adult spinal deformity (ASD) patients and provided recommendations on
      the approach based on degree of axial rotation. In order to isolate vertebral
      rotation (VR) impact from the superimposed degenerative cascade observed in
      adulthood, adolescent idiopathic scoliosis (AIS) patients were analyzed. Methods:
      Magnetic resonance imaging (MRI) scans (L1-S1) from 50 right-convex thoracic
      (left-convex lumbar) AIS patients were analyzed. At each intervertebral level,
      VR, lumbar plexus depth (LPD), and vascular structure depth (VSD) were evaluated.
      Paired t test analyses were used to describe anatomic differences between the
      concave and convex aspect of our patients' curves. Correlation analysis was used
      to investigate relationships with soft tissue modifications and VR. Results:
      Fifty AIS patients (17M, 33F) with mean thoracic Cobb of 50.6 degrees  +/- 17.0
      degrees  and mean lumbar Cobb of 41.9 degrees  +/- 13.0 degrees  were included.
      Mean VR at each level was L1-2 = -6.6 degrees , L2-3 = -7.7 degrees , L3-4 = -6.5
      degrees , L4-5 = -4.7 degrees , L5-S1 = -2.6 degrees  (negative value denotes
      clockwise rotation). We found significant differences (P < .05) between concave
      convex (right-left) LPD at each level (L1-2 = 3.7 mm, L2-3 = 5.1 mm, L3-4 = 4.2
      mm, L4-5 = 2.2 mm, L5-S1 = 2.2 mm). Vascular structure depth was significantly
      different at L1-L2 (3.2 mm) and L5-S1 (3 mm). Significant correlation was found
      between increasing VR and concave-convex LPD difference (r = 0.68, P < .001).
      Conclusions: This study demonstrates that displacement of the lumbar plexus is
      tied to the magnitude of VR in patients with AIS. When approaching the lumbar
      spine, this displacement widens the safe surgical corridor on the convex side and
      narrows the corridor on the concave side. Level of Evidence: IV. Clinical
      Relevance: Preoperative review of MRI scans should occur to assess the patient's
      safe surgical corridor for lateral lumbar interbody fusion (LLIF). Adult spinal
      deformity surgeons who approach a degenerated spine in patients with progressive
      AIS in adulthood must carefully plan for patient positioning, neurovascular
      anatomy, and realignment objectives prior to the day of surgical intervention.

PMID- 30280078
TI  - Etiology and Management of Spinal Deformity in Patients With Parkinson's Disease.
AB  - Patients with Parkinson's disease (PD) commonly develop severe spinal deformity,
      including scoliosis, antecollis, camptocormia, and Pisa syndrome. The etiology of
      PD-associated spinal deformity is not completely understood and in most cases is
      likely due to multiple interrelated factors, including central dystonia and focal
      myopathy. Once spinal deformity has occurred, surgery is often the only modality
      that can correct the condition, although control of the movement disorder through
      medication and deep brain stimulation may slow progression. Advances in spinal
      instrumentation and deformity correction techniques have improved the outcomes of
      PD spinal deformity patients, though complications and revision surgery rates
      remain high. Surgical intervention is reserved for individuals who are
      physiologically healthy and whose condition is refractory to nonoperative
      management and follows similar treatment principles as other causes of
      neuromuscular scoliosis/kyphosis. Spinal deformity patients with PD are optimally
      treated by spinal deformity surgeons who are familiar with the unique needs of PD
      patients, with vigilant preoperative and postoperative treatment of their
      movement disorder and bone density.

PMID- 30280079
TI  - Spontaneous Epidural Hematoma of Cervical Spine.
AB  - Spontaneous cervical epidural hematoma is an uncommon cause of acute spinal cord
      compression. This is a rare idiopathic condition that leads to acute onset of
      neurologic deficits, which if not recognized early can have catastrophic
      consequences. Acute cervical epidural hematoma is definitely a condition of
      neurologic emergency. Although it is a rare condition, it must be considered in
      nontraumatic patients with sudden onset of neurologic deficits. Patients with
      spontaneous spinal epidural hematoma typically present with acute onset of severe
      back pain, and they rapidly develop signs of compression of the spinal cord or
      cauda equina. Here, we present a case of a 31-year-old man who presented with
      acute onset of neck pain with radicular component with progressive neurologic
      deficit. Emergent magnetic resonance imaging revealed cervical extradural
      hematoma with cord compression that was promptly evacuated. Functional recovery
      was achieved within 48 hours. The level of preoperative neurologic deficit and
      its severity, as well as operative interval, are important factors significantly
      affecting the postoperative outcome.

PMID- 30280080
TI  - Radiologic Analysis of C2 to Predict Safe Placement of Pedicle Screws.
AB  - Background: Preoperative assessment of C2 pedicle morphology is critical to safe
      pedicle screw placement. To avoid iatrogenic injury, complex digital templating
      software has been introduced; however, this technology may not be available in
      many centers. We report a technique for preoperative assessment of C2 pedicle
      screw placement safety based upon 2-dimensional sagittal computed tomography (CT)
      scan images and verify its utility in clinical practice. Methods: A total of 46
      consecutive patients underwent cervical spine CT scans between 2005 and 2011. The
      C2 pedicle morphology was assessed on sagittal CT imaging by 5 independent
      reviewers to determine the feasibility and risk associated with pedicle screw
      placement. Thirty consecutive patients underwent C2 pedicle screw placement and
      were followed clinically for a minimum of 2 years. The ability to place a screw
      was noted, and accuracy of screw placement was assessed postoperatively by CT
      scan. Results: The CT scan analysis demonstrated that 11% (5/46) of patients had
      sufficient pedicle size bilaterally to allow safe placement of long pedicle
      screws with a low risk of vertebral artery injury, whereas 15% (7/46) were
      considered a high risk bilaterally. Screw placement was deemed low risk in 28%,
      moderate risk in 38%, and high risk in 34%. Excellent intraobserver reliability
      and good interobserver reliability was observed. Clinically, 18 of 20 (90%) low
      risk and 21 of 24 (88%) moderate-risk pedicle screws were placed safely versus 5
      of 16 (31%) high-risk pedicle screws (P < .001). Conclusions: Using the described
      technique for evaluating the C2 pedicle via sagittal CT scan images allows for
      safe and reliable pedicle screw placement without relying upon complex digital
      templating software, which may have limited availability. Level of Evidence: II.
      Clinical Relevance: This study aids in the surgical decision-making behind the
      placement of C2 pedicle screws using CT scans without reliance upon complex
      digital templating software.

PMID- 30280081
TI  - Physician-Specific Variability in Spine Fusion Patients.
AB  - Background: It is often assumed that each surgeon's patient population is similar
      to that of his or her peers. Differences in patient characteristics naturally may
      lead to diverse outcomes. To date, the variability of individual surgeons'
      patient populations has not been adequately characterized. The purpose of this
      study is to describe the variation in physician-specific patient characteristics
      among surgeons performing spine fusion surgery at a large, urban academic medical
      center. Methods: We analyzed administrative data from a single institution for
      spine fusion surgery from 2009 to 2013. There were 6585 primary and 362 revision
      cases of spine fusion performed within this time period. Variability between
      surgeons and their respective patient populations was compared using descriptive
      statistics. Results: The mean annual percentage of primary fusion patients with
      diabetes mellitus ranged from 0 to 16.17% (mean +/- SD, 7.79% +/- 3.96%) but
      constituted anywhere from 0 to 41.58% (mean +/- SD, 8.15% +/- 12.09%) of revision
      fusions. The mean annual percentage of primary fusion patients who were obese
      ranged from 0 to 9% (mean +/- SD, 2.95% +/- 2.7%), and 0 to 25% in revision cases
      (mean +/- SD, 3.43% +/- 6.43%). The annual mean percentage of patients with
      American Society of Anesthesiologists (ASA) scores greater than 3 ranged from
      8.8% to 44.43% (mean +/- SD, 20.42% +/- 8.85%) in primary fusions and 0 to 100%
      (mean +/- SD, 32.79% +/- 23.47%) in revision fusions. Conclusion: There was a
      large amount of variability among surgeons' patient populations when looking at
      characteristics such as obesity, diabetes, and ASA scores >3. These factors have
      been shown to impact patient outcomes. The variability in the patient populations
      of individual surgeons' practices even within the same medical center must be
      taken into account when evaluating physician specific outcomes and quality of
      care.

PMID- 30280082
TI  - Enchondroma Protuberans of the Transverse Process of D8 Vertebra Extending to the
      7th and 8th Ribs: A Rare Case Report.
AB  - Background: Enchondroma protuberans (EP) is rare, benign cartilaginous bone tumor
      arising from the intramedullary cavity of long bones and usually protrudes beyond
      the cortex with an exophytic growth pattern resembling osteochondroma. This study
      reports on a rare case of EP arising from the transverse process of the D8
      vertebra and extending to the adjacent 7th and 8th ribs and the paraspinal
      tissues. Methods: A 45-year-old female patient came in with complaints of upper
      back pain radiating up to the left costal margin for the past 6 months. There
      were no parasthesias, and there was no history of any sensory or motor symptoms.
      On physical examination there was midline and left paraspinal tenderness over the
      D6 to D8 region. Anteroposterior and lateral X-ray images revealed a well-defined
      oval ossific mass lesion over the lateral aspect of the D8 vertebra, extending to
      the 7th and 8th ribs on the left side, and multiple bridging osteophytes were
      noted. Computed tomography scan showed an ossific mass lesion arising from the D8
      transverse process with extension to the adjacent 7th and 8th ribs; its margins
      were well defined, with no periosteal reaction. Magnetic resonance imaging showed
      a well-defined expansile mass lesion arising from the transverse process of the
      D8 vertebra matrix; it was was isointense with adjacent marrow and had no
      evidence of calcifications or vascular flow voids and no encroachment into the
      spinal canal. Results: Complete resection of the mass lesion with the adjacent
      part of the 7th and 8th ribs and with intramedullary curettage was performed and
      sent for histopathologic examination. Histopathology showed bony trabeculae with
      normal mucosal elements, and a mild hypercellularity with binucleation.
      Chondrocytes in the myxoid matrix located in round lacunae were compatible with
      enchondroma, with no evidence of atypia. The postoperative period was uneventful,
      and after 12 months there were no signs of recurrence noted in computed
      tomography scan. Conclusions: EP is a rare presentation in the dorsal spine; it
      should be considered in the differential diagnosis of osteochondroma,
      enchondroma, chondrosarcoma, and periosteal chondroid tumors.

PMID- 30280083
TI  - Elastomeric Lumbar Total Disc Replacement: Clinical and Radiological Results With
      Minimum 84 Months Follow-Up.
AB  - Background: Total lumbar disc replacement (TDR) devices have been designed to
      maintain motion, but both biomechanical and clinical data have indicated that a
      more controlled motion and additional load absorption in TDR would be beneficial.
      This work analyzed long-term results of an elastomeric disc (Physio-L) for
      degenerative lumbar conditions. Material and Methods: This was a prospective,
      noncomparative, single-center clinical and radiological study. A total of 15
      patients with predominant low back pain due degenerative disc disease received
      anterior total disc replacement with a Physio-L disc. Clinical outcomes were
      assessed both with a visual analog scale for pain and Oswestry Disability Index
      questionnaires. Radiological outcomes included implant failure, range of motion
      (ROM), facet degeneration, and adjacent level disease. Complication and
      reoperation rates were also recorded. The cases were assessed with a minimum
      follow-up of 84 months. Results: A total of 15 patients were enrolled (20 TDRs)
      10 single-level cases (L5S1) and 5 two-level cases (L4L5/L5S1). After 84 months,
      clinical outcomes scores still demonstrated significant improvement compared with
      baseline (P < .001). Mean visual analog scale scores dropped from 7.1 to 2.9, and
      the Oswestry Disability Index improved from 50 to 16. No disc has experienced
      migration or breakage. The average range of motion value went from a baseline of
      12.0 degrees  to 13.3 degrees  at 12 months, and at the final follow-up it
      decreased to 9.9 degrees . Regarding the double-level cases, 3 of 5 (60%) had
      adverse events; just 1 single-level (10%) had adverse events. At final follow-up,
      radiological signs of facet degeneration were present in 7 of 15 patients (47%)
      but with only 1 of 15 (6.7%) symptomatic. Two patients (13%) required surgery at
      the adjacent level. At the 84-month follow-up, 16 of 18 prostheses (89%) were
      still active (2 revised to fusion and 2 were lost to follow-up). Conclusion: The
      long-term follow-up data shows satisfactory clinical results for the use of
      Physio-L elastomeric TDR in the treatment of degenerative disc disease. Studies
      with bigger cohorts are needed to replicate results and add new information
      regarding other details.

PMID- 30280084
TI  - A Prospective Analysis of the Supine and Sitting Straight-Leg Raise Test and Its
      Performance in Litigation Patients.
AB  - Background: The supine straight-leg raise (SLR) test has the potential to be
      exploited by malingering patients. The sitting SLR is believed to be less
      recognizable, therefore decreasing the chance of fabrication. The authors aim to
      compare the supine and sitting SLR test in patients with radiculopathy. Methods:
      A total of 107 patients with radiculopathy were included in this study. Two
      groups were created: patients with workman's compensation (Group 1) and a control
      group of patients without litigation claims (Group 2). Results: Mean age was 47.3
      +/- 1.3 years with a 51% female population. Correlation analysis demonstrated
      association between mean angles in both positions, r = 0.248 with significance P
      = .01. There was equivalence in the mean angles in sitting position of 37 +/- 3
      degrees  compared to 35 +/- 2 degrees  in supine position (P = .549). There was
      no significant difference in the mean angle at which the test became positive in
      the litigation group in the sitting or supine position compared to the
      nonlitigation group, P = .616 and P = .49 respectively. Conclusion: This study
      demonstrated that the SLR test is equivalent in the sitting and supine position.
      Therefore, patients with a positive test should have similar angles in both
      positions, decreasing the chance of falsifying the examination. Level of
      Evidence: Prospective analysis. Clinical Relevance: Clinical practice.

PMID- 30280085
TI  - Spinal Stenosis in the Absence of Spondylolisthesis: Can Interlaminar
      Stabilization at Single and Multi-levels Provide Sustainable Relief?
AB  - Background: In the absence of spondylolisthesis, fusion procedures are generally
      not recommended. However, decompression alone often does not provide long-term
      clinical success of intractable leg and back pain. Decompression with
      interlaminar stabilization (ILS) offers a new option within the clinical
      continuum of care by providing a nonfusion surgical alternative. The objective of
      this study is to examine the sustainability of decompression with ILS and to
      understand the clinical success at either 1 or 2 levels as a surgical treatment
      for nonspondylolisthesis patients with spinal stenosis. Methods: Under an FDA
      regulated investigational device exemption (IDE) study, a total of 322 patients
      were enrolled in the prospective, randomized trial. This investigation focuses
      only on the subset of patients (116 total) from this overall cohort who were
      treated with decompression plus ILS at 1 or 2 levels and who did not present with
      spondylolisthesis preoperatively. The patients were assessed before and after
      surgery up to 60 months. Results: At 60-month follow up, there was no
      statistically significant difference in ODI >= 15 point improvement between
      patient populations (81.6% of 1 level, 90.3% of 2 level). At 60 months, 83.1% of
      1 level and 86.3% of 2 level patients did not require a secondary surgical
      procedure. At 60 months, 94.7% of 1 level and 100% of 2 level reported >=20 mm
      improvement in Visual Analogue Scale leg pain. Patients reported improvement in
      their physical state according to Short Form-12 scores (89.3% of 1 level, 88.9%
      of 2 level). Patient satisfaction at 60 months was 97.4% for 1 level and 93.3%
      for 2 level. Conclusions: The therapeutic sustainability for the treatment of
      spinal stenosis without spondylolisthesis with ILS at 1 or 2 levels in the lumbar
      region has been shown to be safe and efficacious for patients who have failed
      conservative treatment. Clinical Relevance: Decompression with ILS offers a
      nonterminal surgical option for the treatment of the symptomology of spinal
      stenosis, a progressive degenerative condition, that potentially can provide
      longer durability and stability than decompression alone.

PMID- 30280086
TI  - Transforaminal Lumbar Interbody Fusion With Local Bone Graft Alone for Single
      Level Isthmic Spondylolisthesis.
AB  - Background: A retrospective study of patients treated by transforaminal lumbar
      interbody fusion (TLIF) with local bone graft alone for single-level isthmic
      spondylolisthesis (IS) between April 2009 and July 2014 in a single facility.
      Methods: Demographic and operative data, complications, preoperative and
      postoperative clinical records, and radiographs were revised. The Visual Analogue
      Scale (VAS) and Denis Work Scale were used for clinical and functional
      assessment. Modified Lee et al. classification was used for assessment of union.
      Results: Twenty-three patients with mean age of 45.04 +/- 7.19 years had single
      level TLIF with local bone graft alone for symptomatic IS with mean follow-up
      period of 28.39 +/- 4.01 months and mean operative time of 170.09 +/- 11.22
      minutes. The VAS and Denis Work Scale improved from 8.48 +/- 0.58 and 4.67 +/-
      0.47 preoperative to 2.91 +/- 1.25 and 1.33 +/- 0.58 at the latest follow up,
      respectively. Anterior vertebral translation improved from 27.22 +/- 9.54%
      preoperatively to 8.38 +/- 3.63% postoperatively and 10.39 +/- 3.49 at the latest
      follow up. Disc space height was 9.67 +/- 5.55% preoperatively, 21.60 +/- 4.11%
      postoperative, and 16.24 +/- 4.02% at the latest follow up. Lumbar lordosis
      improved from 29.39 +/- 10.33 degrees  to 45.13 +/- 6.84 degrees  postoperatively
      and 39.96 +/- 7.52 degrees  at the latest follow up. Eighteen patients had
      definitive union, 4 patients with possible union, 1 patient with possible
      pseudoarthrosis. Conclusions: Transforaminal lumbar interbody fusion with local
      bone graft alone is an appropriate option for single-level IS, yet we do not
      recommend it for higher grades of slippage with anterior vertebral translation
      more than 25%.

PMID- 30280087
TI  - Transforaminal Lumbar Interbody Fusion With Viable Allograft: 75 Consecutive
      Cases at 12-Month Follow-up.
AB  - Background: When conservative treatments fail to alleviate the discomfort of
      abnormal motion, spinal fusion has been shown to provide symptomatic treatment
      for spinal instability, stenosis, spondylolisthesis, and symptomatic degenerative
      disc disease. The trend and rates of fusion over the past few years have been
      dramatic in the United States. Accompanying that higher incidence has been the
      shifting from traditional open surgery to minimally invasive techniques to reduce
      scar tissue formation, extent of muscle stripping, and muscle retraction which
      all have been shown to adversely affect outcomes. Other reasons supporting the
      widespread transition to minimally invasive surgical (MIS) techniques include
      decreased postoperative pain, decreased intraoperative blood loss, shorter
      postoperative hospital stay, faster return to normal activity, and reduced
      reoperation rates. Spinal fusion procedures rely on a bony fusion substrate in
      addition to fixation hardware. While available grafting options include
      autogenous, allogeneic, and synthetic materials, recent interest in viable
      allograft material with living cells has drawn attention and attraction for
      incorporating a biologic basis for regenerative consideration. A recent viable
      allograft, complete with cellular and designated bone carrier (VIA Graft, Vivex
      Biomedical, Marietta, Georgia) has been developed. This study represents a
      retrospective review of a single-practice, single-surgeon evaluation of the
      product in 75 consecutive patients for fusion by computed tomography (CT) and
      radiographic evaluation at 12 months in conjunction with a MIS approach. Viable
      allograft was used to fill the peri-implant space, and central implant lumen was
      filled with a cancellous bone sponge soaked in perivertebral bone marrow.
      Posterolateral supplementation was attained with beta-tricalcium phosphate as a
      bulking agent. Methods: A retrospective review identified patients treated for
      both primary and revision surgery who received VIA Graft cellular bone matrix
      material in minimally invasive interbody fusion (MIS-TLIF) with a minimum of 12
      month follow up. The patient diagnoses included radiculopathy in all instances
      and varied collateral indications such as foraminal collapse, recurrent disc
      herniation, and spondylolisthesis to which pain and morbidity had been unresolved
      by conservative treatment. Adverse events including infection, revisions, and
      evidence of immune response were evaluated and patient comorbidities defined for
      the entire population of patients. Patient fusion status was assessed using thin
      slice CT by 2 independent radiologists separate from the surgeon. There were 75
      consecutive adult patients with degenerative conditions of the lumbar spine who
      underwent MIS-TLIF surgery of which 40 (53%) were male and 35 (47%) were female.
      Mean age, height, and weight were 58 years, 170.18 cm (67 in), and 88.45 kg (195
      lbs), respectively. The mean body mass index was 30. There were 16 patients (21%)
      who smoked and 12 (16%) with a history of diabetes. Independent blinded review of
      fusion was obtained by a board certified musculoskeletal radiologist and an
      experienced board certified orthopaedic surgeon to assess patient fusion status.
      Spinal segments were deemed fused if 12-month CT scans demonstrated evidence of
      bridging bone at the fusion site without observed motion on flexion-extension
      radiographs. Findings such as osteolysis around the implant or pedicle screws,
      extensive endplate cystic changes, or linear defects parallel to the endplates
      through intradiscal new bone formation were interpreted as signs of
      pseudarthrosis. Interobserver and intraobserver error and kappa assessments were
      analyzed to assure agreement in the CT outcomes assessment where interpretation
      of kappa were as follows: <0.00 = poor agreement, 0.00-0.20 = slight agreement,
      0.21-0.40 = fair agreement, 0.41-0.60 = moderate agreement, 0.61-0.80 =
      substantial agreement, and 0.81-1.00 = almost perfect agreement. Differences were
      resolved by consensus amongst the observers. Results: In total, 96% of the 75
      patients with a total of 85 levels (96.5% of levels treated) achieved a fusion at
      12 months. There were no perioperative or latent complications and no
      transfusions in all 75 patients. Conclusions: In this population, 96% of the
      patients treated achieved the surgical objective in 96.5% of the levels treated.
      Level of Evidence: IV. Clinical Relevance: The high rate of fusion, the lack of
      secondary morbidity with autologous bone harvest, and the clinical success
      account for the benefits of viable allograft matrix for MIS-TLIF use.

PMID- 30280088
TI  - Anterior Fixation of Floating Facet Fractures in the Cervical Spine: A
      Prospective Case Series and Biomechanical Analysis.
AB  - Background: Unilateral fractures involving complete separation of the lateral
      mass from the vertebra and lamina (floating lateral mass fractures) are a unique
      subset of cervical spine fractures. These injuries are at significant risk for
      displacement without operative fixation. Posterior fixation has proven to
      facilitate adequate fusion. However, there are few data supporting the clinical
      success of single-level anterior fixation. Methods: Biomechanical evaluation of
      floating lateral mass fractures and a consecutive case series of patients with
      rotationally unstable floating lateral mass fractures treated with anterior
      fixation using an integrated cage-screw device with anterior plating (ICSD) was
      performed. The study comprised 7 fresh human cadaver cervical spines (C2-C7), and
      11 patients with floating lateral mass fractures. Segmental flexibility testing
      evaluating axial rotation, flexion/extension, and lateral bending was performed
      in a cadaveric model after 2 types of single-level anterior fixation and 1 type
      of 2-level posterior fixation. Eleven patients with a floating lateral mass
      fracture of the cervical spine underwent anterior fixation with an ICSD.
      Radiographs and clinical outcomes were retrospectively reviewed. Results:
      Compared with the intact condition, posterior instrumentation significantly (P <
      .05) reduced range of motion (ROM) in all 3 planes; anterior fixation with
      cervical plate and interbody spacer significantly reduced ROM in lateral bending
      only; and the ICSD significantly reduced ROM in flexion/extension and lateral
      bending. In the clinical arm, there were no long-term complications, subsidence
      >2 mm, failure of fixation, reoperation, pseudoarthrosis, or listhesis at final
      follow-up. Conclusions: The addition of 2 screws placed through a cervical cage
      can improve anterior fixation in a human cadaveric model of floating lateral mass
      fractures. Early clinical results demonstrate a low complication rate and a high
      rate of healing with single-level anterior fixation using this technique.

PMID- 30280089
TI  - Corrigendum: Circular RNAs in Cancer - Lessons Learned From microRNAs.
AB  - [This corrects the article DOI: 10.3389/fonc.2018.00179.].

PMID- 30280092
TI  - The Virulence Effect of CpxRA in Citrobacter rodentium Is Independent of the
      Auxiliary Proteins NlpE and CpxP.
AB  - Citrobacter rodentium is a murine pathogen used to model the intestinal infection
      caused by Enteropathogenic and Enterohemorrhagic Escherichia coli (EPEC and
      EHEC), two diarrheal pathogens responsible for morbidity and mortality in
      developing and developed countries, respectively. During infection, these
      bacteria must sense and adapt to the gut environment of the host. In order to
      adapt to changing environmental cues and modulate expression of specific genes,
      bacteria can use two-component signal transduction systems (TCS). We have shown
      that the deletion of the Cpx TCS in C. rodentium leads to a marked attenuation in
      virulence in C3H/HeJ mice. In E. coli, the Cpx TCS is reportedly activated in
      response to signals from the outer-membrane lipoprotein NlpE. We therefore
      investigated the role of NlpE in C. rodentium virulence. We also assessed the
      role of the reported negative regulator of CpxRA, CpxP. We found that as opposed
      to the DeltacpxRA strain, neither the DeltanlpE, DeltacpxP nor the
      DeltanlpEDeltacpxP strains were significantly attenuated, and had similar in vivo
      localization to wild-type C. rodentium. The in vitro adherence of the Cpx
      auxiliary protein mutants, DeltanlpE, DeltacpxP, DeltanlpEDeltacpxP, was
      comparable to wild-type C. rodentium, whereas the DeltacpxRA strain showed
      significantly decreased adherence. To further elucidate the mechanisms behind the
      contrasting virulence phenotypes, we performed microarrays in order to define the
      regulon of the Cpx TCS. We detected 393 genes differentially regulated in the
      DeltacpxRA strain. The gene expression profile of the DeltanlpE strain is
      strikingly different than the profile of DeltacpxRA with regards to the genes
      activated by CpxRA. Further, there is no clear inverse correlation in the
      expression pattern of the DeltacpxP strain in comparison to DeltacpxRA. Taken
      together, these data suggest that in these conditions, CpxRA activates gene
      expression in a largely NlpE- and CpxP-independent manner. Compared to wildtype,
      161 genes were downregulated in the DeltacpxRA strain, while being upregulated or
      unchanged in the Cpx auxiliary protein deletion strains. This group of genes,
      which we hypothesize may contribute to the loss of virulence of DeltacpxRA,
      includes T6SS components, ompF, the regulator for colanic acid synthesis, and
      several genes involved in maltose metabolism.

PMID- 30280090
TI  - The Role of Immunohistochemical Analysis as a Tool for the Diagnosis, Prognostic
      Evaluation and Treatment of Prostate Cancer: A Systematic Review of the
      Literature.
AB  - Background: Prostate cancer (PCa) is a heterogeneous disease that lends itself
      toward numerous therapeutic options depending on its risk stratification. One of
      the greatest challenges in PCa urologic practice is to select patients who should
      be referred for biopsy and, for those patients who are diagnosed with cancer, to
      differentiate between patients with indolent disease from those with an
      unfavorable prognosis and, to determine ideal patient management and avoid
      unnecessary interventions. Accordingly, there is a growing body of literature
      reporting immunohistochemical studies with the objective of determining a
      prostate cancer prognosis. Among the most frequent biomarkers studied are Ki-67,
      p53, PTEN, MYC, and ERG. Based on these findings, we systematically reviewed
      articles that assessed the role of these main prognostic markers in prostate
      cancer. Methods: Consistent with PRISMA guidelines, we performed a systematic
      literature search throughout the Web of Science and PubMed Medline databases. We
      considered all types of studies evaluating the role of Ki-67, p53, PTEN, MYC, and
      ERG immunohistochemical analysis in prostate cancer until July 2017. Results: We
      identified 361 articles, 44 of which were summarized in this review.
      Diagnostically, no single immunohistochemical marker was able to define a tumor
      as benign or malignant. Prognostically, Ki-67, p53, and MYC were related to the
      tumor grade given by Gleason score and to the tumor stage (higher levels related
      to higher tumor grade). Furthermore, Ki-67 was also related to higher PSA levels,
      shorter disease-free intervals and shorter tumor-specific survival; the latter
      was also related to p53. The loss of PTEN protein expression showed a higher
      association with biochemical recurrence and with a worse prognosis, beyond that
      predicted by the Gleason score and tumor stage. ERG staining also showed a strong
      association with biochemical recurrence. Conclusion: There are several studies
      relating immunohistochemical markers with clinical-laboratorial outcomes in
      prostate cancer, the most frequent being Ki-67, p53, ERG, PTEN, and MYC. However,
      none of these markers have been validated by literary consensus to be routinely
      applied in medical practice.

PMID- 30280093
TI  - Yersinia pseudotuberculosis BarA-UvrY Two-Component Regulatory System Represses
      Biofilms via CsrB.
AB  - The formation of biofilms by Yersinia pseudotuberculosis (Yptb) and Y. pestis
      requires the hmsHFRS genes, which direct production of a polysaccharide
      extracellular matrix (Hms-ECM). Despite possessing identical hmsHFRS sequences,
      Yptb produces much less Hms-ECM than Y. pestis. The regulatory influences that
      control Yptb Hms-ECM production and biofilm formation are not fully understood.
      In this study, negative regulators of biofilm production in Yptb were identified.
      Inactivation of the BarA/UvrY two-component system or the CsrB regulatory RNA
      increased binding of Congo Red dye, which correlates with extracellular
      polysaccharide production. These mutants also produced biofilms that were
      substantially more cohesive than the wild type strain. Disruption of uvrY was not
      sufficient for Yptb to cause proventricular blockage during infection of
      Xenopsylla cheopis fleas. However, this strain was less acutely toxic toward
      fleas than wild type Yptb. Flow cytometry measurements of lectin binding
      indicated that Yptb BarA/UvrY/CsrB mutants may produce higher levels of other
      carbohydrates in addition to poly-GlcNAc Hms-ECM. In an effort to characterize
      the relevant downstream targets of the BarA/UvrY system, we conducted a proteomic
      analysis to identify proteins with lower abundance in the csrB::Tn5 mutant
      strain. Urease subunit proteins were less abundant and urease enzymatic activity
      was lower, which likely reduced toxicity toward fleas. Loss of CsrB impacted
      expression of several potential regulatory proteins that may influence biofilms,
      including the RcsB regulator. Overexpression of CsrB did not alter the Congo-red
      binding phenotype of an rcsB::Tn5 mutant, suggesting that the effect of CsrB on
      biofilms may require RcsB. These results underscore the regulatory and
      compositional differences between Yptb and Y. pestis biofilms. By activating CsrB
      expression, the Yptb BarA/UvrY two-component system has pleiotropic effects that
      impact biofilm production and stability.

PMID- 30280091
TI  - The Redox-Sensing Regulator Rex Contributes to the Virulence and Oxidative Stress
      Response of Streptococcus suis Serotype 2.
AB  - Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen responsible
      for septicemia and meningitis. The redox-sensing regulator Rex has been reported
      to play critical roles in the metabolism regulation, oxidative stress response,
      and virulence of various pathogens. In this study, we identified and
      characterized a Rex ortholog in the SS2 virulent strain SS2-1 that is involved in
      bacterial pathogenicity and stress environment susceptibility. Our data show that
      the Rex-knockout mutant strain Deltarex exhibited impaired growth in medium with
      hydrogen peroxide or a low pH compared with the wildtype strain SS2-1 and the
      complementary strain CDeltarex. In addition, Deltarex showed a decreased level of
      survival in whole blood and in RAW264.7 macrophages. Further analyses revealed
      that Rex deficiency significantly attenuated bacterial virulence in an animal
      model. A comparative proteome analysis found that the expression levels of
      several proteins involved in virulence and oxidative stress were significantly
      different in Deltarex compared with SS2-1. Electrophoretic mobility shift assays
      revealed that recombinant Rex specifically bound to the promoters of target genes
      in a manner that was modulated by NADH and NAD+. Taken together, our data suggest
      that Rex plays critical roles in the virulence and oxidative stress response of
      SS2.

PMID- 30280094
TI  - Bovine Epithelial in vitro Infection Models for Mycoplasma bovis.
AB  - Mycoplasma bovis causes bovine mycoplasmosis. The major clinical manifestations
      are pneumonia and mastitis. Recently an increase in the severity of mastitis
      cases was reported in Switzerland. At the molecular level, there is limited
      understanding of the mechanisms of pathogenicity of M. bovis. Host-pathogen
      interactions were primarily studied using primary bovine blood cells. Therefore,
      little is known about the impact of M. bovis on other cell types present in
      infected tissues. Clear in vitro phenotypes linked to the virulence of M. bovis
      strains or tissue predilection of specific M. bovis strains have not yet been
      described. We adapted bovine in vitro systems to investigate infection of
      epithelial cells with M. bovis using a cell line (MDBK: Madin-Darby bovine kidney
      cells) and two primary cells (PECT: bovine embryonic turbinate cells and bMec:
      bovine mammary gland epithelial cells). Two strains isolated before and after the
      emergence of severe mastitis cases were selected. Strain JF4278 isolated from a
      cow with mastitis and pneumonia in 2008 and strain L22/93 isolated in 1993 were
      used to assess the virulence of M. bovis genotypes toward epithelial cells with
      particular emphasis on mammary gland cells. Our findings indicate that M. bovis
      is able to adhere to and invade different epithelial cell types. Higher titers of
      JF4278 than L22/93 were observed in co-cultures with cells. The differences in
      titers reached between the two strains was more prominent for bMec cells than for
      MDBK and PECT cells. Moreover, M. bovis strain L22/93 induced apoptosis in MDBK
      cells and cytotoxicity in PECT cells but not in bMec cells. Dose-dependent
      variations in proliferation of primary epithelial cells were observed after M.
      bovis infection. Nevertheless, an indisputable phenotype that could be related to
      the increased virulence toward mammary gland cells is not obvious.

PMID- 30280096
TI  - Ubiquitin Receptor RPN13 Mediates the Inhibitory Interaction of
      Diphenyldihaloketones CLEFMA and EF24 With the 26S Proteasome.
AB  - The proteasome is a validated target in drug discovery for diseases associated
      with unusual proteasomal activity. Here we report that two diphenyldihaloketones,
      CLEFMA and EF24, inhibit the peptidase activity of the 26S proteasome. The
      objective of this study was to investigate interaction of these compounds with
      the proteasome and identify a putative target within the protein components of
      the 26S proteasome. We employed standard fluorogenic peptide-based proteasome
      activity assay for trypsin-like, chymotrypsin-like, and caspase-like activities
      of human purified 26S proteasome in cell-free conditions. GFPu-1 and HUVEC cells
      were used as proteasome reporter cells. Direct binding studies used purified 19S,
      20S, 26S, and recombinant RPN13-Pru for interaction with biotinylated analogs of
      CLEFMA and EF24. The reaction mixtures were subjected to horizontal gel
      electrophoresis, streptavidin-blotting, pull-down assays, and immunoblotting. The
      identity of the interacting protein was determined by 2D gel electrophoresis and
      LC-MS/MS. Drug affinity responsive target stability technique was utilized to
      examine if CLEFMA binding confers protection to RPN13 against thermolysin
      catalyzed proteolysis. We found that trypsin-and chymotrypsin-like activities of
      the 26S proteasome were reduced significantly by both compounds. The compounds
      also reduced the proteolytic activity in GFPu-1 and HUVEC cells, resulting in
      accumulation of ubiquitinated proteins without affecting the autophagy process.
      From direct binding assays a 43 kDa protein in the 26S proteasome was found to be
      the interacting partner. This protein was identified by tandem mass spectroscopy
      as regulatory particle subunit 13 (RPN13), a ubiquitin receptor in the 19S
      regulatory particle. Furthermore, binding of CLEFMA to RPN13 did not protect
      latter from thermolysin-mediated proteolysis. Together, this study showed
      diphenyldihaloketones as potential proteasome inhibitors for treatment of
      diseases with perturbed proteasome function. The results also unraveled RPN13 as
      a unique target of CLEFMA and EF24. As a result, these compounds inhibit both
      trypsin-like and chymotrypsin-like proteasome activities.

PMID- 30280098
TI  - Abundantly Present miRNAs in Milk-Derived Extracellular Vesicles Are Conserved
      Between Mammals.
AB  - Mammalian milk is not only a source of nutrition for the newborn, but also
      contains various components that regulate further development. For instance, milk
      is an abundant source of microRNAs (miRNAs), which are evolutionary conserved
      small non-coding RNAs that are involved in post-transcriptional regulation of
      target mRNA. MiRNAs present in milk can occur in extracellular vesicles (EVs),
      which are nanosized membrane vesicles released by many cell types as a means of
      intercellular communication. The membrane of EVs protects enclosed miRNAs from
      degradation and harbors molecules that allow specific targeting to recipient
      cells. Although several studies have investigated the miRNA content in milk EVs
      from individual species, little is known about the evolutionary conserved nature
      of EV-associated miRNAs among different species. In this study, we profiled the
      miRNA content of purified EVs from human and porcine milk. These data were
      compared to published studies on EVs from human, cow, porcine, and panda milk to
      assess the overlap in the top 20 most abundant miRNAs. Interestingly, several
      abundant miRNAs were shared between species (e.g., let-7 family members let-7a,
      let-7b, let-7f, and miR-148a). Moreover, these miRNAs have been implicated in
      immune-related functions and regulation of cell growth and signal transduction.
      The conservation of these miRNA among species, not only in their sequence
      homology, but also in their incorporation in milk EVs of several species,
      suggests that they are evolutionarily selected to regulate cell function in the
      newborn.

PMID- 30280097
TI  - Analysis of the Transcriptome in Aspergillus tamarii During Enzymatic Degradation
      of Sugarcane Bagasse.
AB  - The production of bioethanol from non-food agricultural residues represents an
      alternative energy source to fossil fuels for incorporation into the world's
      economy. Within the context of bioconversion of plant biomass into renewable
      energy using improved enzymatic cocktails, Illumina RNA-seq transcriptome
      profiling was conducted on a strain of Aspergillus tamarii, efficient in biomass
      polysaccharide degradation, in order to identify genes encoding proteins involved
      in plant biomass saccharification. Enzyme production and gene expression was
      compared following growth in liquid and semi-solid culture with steam-exploded
      sugarcane bagasse (SB) (1% w/v) and glucose (1% w/v) employed as contrasting sole
      carbon sources. Enzyme production following growth in liquid minimum medium
      supplemented with SB resulted in 0.626 and 0.711 UI.mL-1 xylanases after 24 and
      48 h incubation, respectively. Transcriptome profiling revealed expression of
      over 7120 genes, with groups of genes modulated according to solid or semi-solid
      culture, as well as according to carbon source. Gene ontology analysis of genes
      expressed following SB hydrolysis revealed enrichment in xyloglucan metabolic
      process and xylan, pectin and glucan catabolic process, indicating up-regulation
      of genes involved in xylanase secretion. According to carbohydrate-active enzyme
      (CAZy) classification, 209 CAZyme-encoding genes were identified with significant
      differential expression on liquid or semi-solid SB, in comparison to equivalent
      growth on glucose as carbon source. Up-regulated CAZyme-encoding genes related to
      cellulases (CelA, CelB, CelC, CelD) and hemicellulases (XynG1, XynG2, XynF1,
      XylA, AxeA, arabinofuranosidase) showed up to a 10-fold log2FoldChange in
      expression levels. Five genes from the AA9 (GH61) family, related to lytic
      polysaccharide monooxygenase (LPMO), were also identified with significant
      expression up-regulation. The transcription factor gene XlnR, involved in
      induction of hemicellulases, showed up-regulation on liquid and semi-solid SB
      culture. Similarly, the gene ClrA, responsible for regulation of cellulases,
      showed increased expression on liquid SB culture. Over 150 potential transporter
      genes were also identified with increased expression on liquid and semi-solid SB
      culture. This first comprehensive analysis of the transcriptome of A. tamarii
      contributes to our understanding of genes and regulatory systems involved in
      cellulose and hemicellulose degradation in this fungus, offering potential for
      application in improved enzymatic cocktail development for plant biomass
      degradation in biorefinery applications.

PMID- 30280099
TI  - Outcome of the "Manchester Groin Repair" (Laparoscopic Totally Extraperitoneal
      Approach With Fibrin Sealant Mesh Fixation) in 434 Consecutive Inguinal Hernia
      Repairs.
AB  - Introduction: This study looks at the outcome of 352 patients that underwent the
      "Manchester groin repair" in the period from 2007 to 2016. The effect of
      laterality on chronic groin pain and the reduction of pain scores post-surgery
      are evaluated as well as the rate of hernia recurrence for the inguinal hernia
      repairs. Methods: The "Manchester groin repair" is a modification of a
      laparoscopic totally extra-peritoneal approach with fibrin sealant mesh fixation.
      Data were collected prospectively. In addition to demographic data and the
      European Hernia Society classification grading of each hernia, pain scores were
      assessed prior to surgery and at 4-6 weeks post-operatively using a ten-point
      visual analog pain scale. Data were collected on a bespoke database and
      differences between time-points analyzed by non-parametric Wilcoxon signed rank
      tests with Kruskal-Wallis rank sum test for three-group comparisons. Significance
      was at the P < 0.05 level. The study was undertaken as an institutional audit.
      Results: Three hundred and fifty two patients underwent TEP repair as per the
      "Manchester Groin Repair" modification during the period of interest with a
      median follow-up period of 109.5 (IQR 57.0-318.5) weeks. Of these 274 (77.8%)
      were for the repair of true hernias and 78 (22.2%) were for inguinal disruptions.
      All inguinal hernia repairs patients were evaluated (254 m, 20 f); median
      [interquartile range] age 50 (39-65) years. There were 75 right inguinal hernias
      (27.4%), 39 Left inguinal hernias (14.2%), and 160 bilateral inguinal hernias
      (58.4%), giving a total of 434 hernia repairs. During follow-up there were 6
      recurrences (1.4%).Of the 274 patients evaluated, 145 (52.9%) had both pre and
      post-operative pain scores available. Median pre-operative pain score was 5 [IQR
      4-7]. Median post-operative pain score was 1 [IQR 1-2]. This difference was
      significant (P < 0.001). Pre-operative pain scores were higher for those with a
      bilateral hernia (median 6 vs. 5 and 4, respectively; P = 0.005), but there was
      no difference in post-operative scores (P = 0.347). One patient (0.3%) presented
      with chronic groin pain (pain after 3 months). Conclusion: This study
      demonstrates that the "Manchester groin repair" provides an excellent repair with
      a low rate of recurrence and low incidence of chronic pain. Longer-term
      evaluation and larger patient series will add to the understanding of the role of
      this procedure in groin hernia repair.

PMID- 30280101
TI  - Response Gene to Complement 32 in Vascular Diseases.
AB  - Response gene to complement 32 (RGC32) is a protein that was identified in rat
      oligodendrocytes after complement activation. It is expressed in most of the
      organs and tissues, such as brain, placenta, heart, and the liver. Functionally,
      RGC32 is involved in various physiological and pathological processes, including
      cell proliferation, differentiation, fibrosis, metabolic disease, and cancer.
      Emerging evidences support the roles of RGC32 in vascular diseases. RGC32
      promotes injury-induced vascular neointima formation by mediating smooth muscle
      cell (SMC) proliferation and migration. Moreover, RGC32 mediates endothelial cell
      activation and facilitates atherosclerosis development. Its involvement in
      macrophage phagocytosis and activation as well as T-lymphocyte cell cycle
      activation also suggests that RGC32 is important for the development and
      progression of inflammatory vascular diseases. In this mini-review, we provide an
      overview on the roles of RGC32 in regulating functions of SMCs, endothelial
      cells, and immune cells, and discuss their contributions to vascular diseases.

PMID- 30280102
TI  - Single telomere length analysis in Ustilago maydis, a high-resolution tool for
      examining fungal telomere length distribution and C-strand 5'-end processing.
AB  - Telomeres play important roles in genome stability and cell proliferation.
      Telomere lengths are heterogeneous and because just a few abnormal telomeres are
      sufficient to trigger significant cellular response, it is informative to have
      accurate assays that reveal not only average telomere lengths, but also the
      distribution of the longest and shortest telomeres in a given sample. Herein we
      report for the first time, the development of single telomere length analysis
      (STELA) - a PCR-based assay that amplifies multiple, individual telomeres - for
      Ustilago maydis, a basidiomycete fungus. Compared to the standard telomere
      Southern technique, STELA revealed a broader distribution of telomere size as
      well as the existence of relatively short telomeres in wild type cells. When
      applied to blm?, a mutant thought to be defective in telomere replication, STELA
      revealed preferential loss of long telomeres, whose maintenance may thus be
      especially dependent upon efficient replication. In comparison to blm?, the trt1?
      (telomerase null) mutant exhibited greater erosion of short telomeres, consistent
      with a special role for telomerase in re-lengthening extra-short telomeres. We
      also used STELA to characterize the 5' ends of telomere C-strand, and found that
      in U. maydis, they terminate preferentially at selected nucleotide positions
      within the telomere repeat. Deleting trt1 altered the 5'-end distributions,
      suggesting that telomerase may directly or indirectly modulate C-strand 5' end
      formation. These findings illustrate the utility of STELA as well as the
      strengths of U. maydis as a model system for telomere research.

PMID- 30280100
TI  - Mapping and Ablation of Idiopathic Ventricular Fibrillation.
AB  - Idiopathic ventricular fibrillation (IVF) is the main cause of unexplained sudden
      cardiac death, particularly in young patients under the age of 35. IVF is a
      diagnosis of exclusion in patients who have survived a VF episode without any
      identifiable structural or metabolic causes despite extensive diagnostic testing.
      Genetic testing allows identification of a likely causative mutation in up to 27%
      of unexplained sudden deaths in children and young adults. In the majority of
      cases, VF is triggered by PVCs that originate from the Purkinje network. Ablation
      of VF triggers in this setting is associated with high rates of acute success and
      long-term freedom from VF recurrence. Recent studies demonstrate that a
      significant subset of IVF defined by negative comprehensive investigations,
      demonstrate in fact subclinical structural alterations. These localized
      myocardial alterations are identified by high density electrogram mapping, are of
      small size and are mainly located in the epicardium. As reentrant VF drivers are
      often colocated with regions of abnormal electrograms, this localized substrate
      can be shown to be mechanistically linked with VF. Such areas may represent an
      important target for ablation.

PMID- 30280095
TI  - Viral Sepsis in Children.
AB  - Sepsis in children is typically presumed to be bacterial in origin until proven
      otherwise, but frequently bacterial cultures ultimately return negative. Although
      viruses may be important causative agents of culture-negative sepsis worldwide,
      the incidence, disease burden and mortality of viral-induced sepsis is poorly
      elucidated. Consideration of viral sepsis is critical as its recognition carries
      implications on appropriate use of antibacterial agents, infection control
      measures, and, in some cases, specific, time-sensitive antiviral therapies. This
      review outlines our current understanding of viral sepsis in children and
      addresses its epidemiology and pathophysiology, including pathogen-host
      interaction during active infection. Clinical manifestation, diagnostic testing,
      and management options unique to viral infections will be outlined.

PMID- 30280103
TI  - Temporal analysis of the autophagic and apoptotic phenotypes in Leishmania
      parasites.
AB  - The leishmaniases are worldwide neglected tropical diseases caused by parasitic
      protozoa of the Leishmania genus. Different stimuli induce Leishmania cell death,
      but the proteins involved remain poorly understood. Furthermore, confusion often
      appears between cell death and the cell survival process autophagy, whose
      phenotype is not clearly defined. In this article, we present a comprehensive and
      temporal analysis of the cellular events occurring during miltefosine-induced
      cell death and autophagy in L. major. We also provide a list of features in order
      to clearly identify apoptotic cells, autophagic cells and to distinguish both
      processes. Furthermore, we demonstrate that autophagy is followed by apoptosis in
      the absence of nutrients. Finally, we show that cells treated with the generic
      kinase inhibitor staurosporine express apoptotic as well as autophagic markers
      and therefore cannot be used as an apoptosis inducer in Leishmania. These
      descriptions lead to a better recognition and understanding of apoptosis and
      autophagy, enabling their targeting in the development of new anti-leishmanial
      drugs. These researches also make it possible to better understand these
      processes in general, through the study of an ancestral eukaryote.

PMID- 30280104
TI  - Escherichia coli hijack Caspr1 receptor to invade cerebral vascular and neuronal
      hosts.
AB  - Escherichia coli (E. coli) penetration of the blood-brain barrier (BBB) is the
      key step essential for the development of meningitis. In a recent paper (Nat
      Commun 9:2296), we identify Caspr1 as a host receptor for E. coli virulence
      factor IbeA to pave the way the penetration of bacteria through the BBB.
      Bacterial IbeA interacts with endothelial Caspr1 to trigger intracellular focal
      adhesion kinase activation, leading to E. coli internalization into the brain
      endothelial cells. Importantly, endothelial knockout of Caspr1 in mice
      significantly reduced E. coli crossing through the BBB. Based on the results that
      extracellular aa 203-355 of Caspr1 bind with IbeA, we tested the blocking effect
      of recombinant Caspr1(203-355) peptides in neonatal rat model of meningitis. The
      results showed that Caspr1(203-355) peptides effectively attenuated E. coli
      penetration into the brain during meningitis, indicating that Caspr1(203-355)
      peptides could be used to neutralize the virulent IbeA to prevent meningitis. We
      further found that E. coli can directly invade into hippocampal neurons causing
      apoptosis which required the interaction between bacterial IbeA and neuronal
      Caspr1. These findings demonstrate that E. coli hijack Caspr1 as a host receptor
      for penetration of BBB and invasion of hippocampal neurons, resulting in
      progression of meningitis.

PMID- 30280105
TI  - Toxin release mediated by the novel autolysin Cwp19 in Clostridium difficile.
AB  - Clostridium difficile, also known as Clostriodioides difficile, is a Gram
      positive, spore-forming bacterium and a leading cause of antibiotic-associated
      diarrhea in nosocomial environments. The key virulence factors of this pathogen
      are two toxins, toxin A and toxin B, released from the cells to the gut and
      causing colonic injury and inflammation. Although their mechanism of action is
      well known, the toxins A and B have no peptide signals and their secretion
      mechanisms involving the holin-like protein TcdE and autolysis are still under
      active investigation. Autolysis is primarily mediated by peptidoglycan
      hydrolases, an important group of enzymes that cleave covalent bonds in the cell
      wall peptidoglycan. Peptidoglycan hydrolases are essential for peptidoglycan
      remodeling but most of them also have the potential to lyse the cells under
      various conditions. In a recent report by Wydau-Dematteis et al. (MBio 9(3):
      e00648-18), we characterized a novel peptidoglycan hydrolase Cwp19 in C.
      difficile. Importantly, Cwp19 mediates toxins secretion in a glucose-dependent
      fashion suggesting a potential role in C. difficile pathogenesis. Peptidoglycan
      hydrolases are not very well characterized in C. difficile despite the important
      role of these enzymes in cell division and sporulation as shown in model
      organisms like Bacillus subtilis. In addition, these enzymes can be implicated in
      pathogenicity as exemplified by the release of pneumococcal virulence factors.

PMID- 30280106
TI  - Spontaneous Intramural Esophageal Rupture: An Uncommon Presentation of
      Eosinophilic Esophagitis Requiring Endoscopic Clipping.
AB  - Spontaneous intramural esophageal rupture (SIER) is a form of acute esophageal
      trauma defined as an injury deeper than a Mallory-Weiss tear but not extending
      completely through the muscular propria as in Boerhaave syndrome. SIER is a rare
      complication of eosinophilic esophagitis (EoE); after extensive literature
      review, we found 7 case reports of SIER complicating EoE. We present a case of
      SIER complicating EoE in a 46-year-old man with an atypical presentation
      requiring endoscopic clipping to achieve successful hemostasis.

PMID- 30280107
TI  - Osteomyelitis as a Result of Pancreaticojejunostomy Stent Migration after Whipple
      Procedure.
AB  - Pancreaticoduodenectomy, or Whipple procedure, is a high-risk surgical procedure
      commonly performed for tumors of the pancreatic head. The pancreatico-enteric
      anastomosis is an important component of this procedure. The maturation and
      adequate healing of this anastomotic site is critical to decrease the risk of
      postoperative pancreatic fistulas. The use of stents can help in the healing of
      this anastomotic site. We present a patient with pancreatic adenocarcinoma who
      underwent pancreaticoduodenectomy, and presented with progressively worsening
      lumbar pain 7 years later. The patient was found to have osteomyelitis as a
      complication from an entero-spinal fistula secondary to a migrated pediatric
      feeding tube that was placed at the pancreaticojejunal anastomosis.

PMID- 30280108
TI  - Endoscopic Doppler Probe in the Diagnosis and Management of Upper
      Gastrointestinal Hemorrhage.
AB  - Through-the-scope (TTS) endoscopic Doppler ultrasound probe technology is a tool
      that has garnered interest for the evaluation of variceal and non-variceal
      bleeding. In previous studies, this technology has been proposed as a more
      objective method of identifying the bleeding subsurface blood vessel in peptic
      ulcer hemorrhage. We describe 3 cases where the use of an endoscopic Doppler
      probe guided the diagnosis and management of upper gastrointestinal (GI)
      hemorrhage due to causes other than peptic ulcer disease. The first case
      describes a patient with a duodenal Dieulafoy lesion, while the other 2 cases
      outline patients with a gastroesophageal varix as the etiology of the bleed.

PMID- 30280109
TI  - Intragastric Balloon Hyperinsufflation as a Cause of Acute Obstructive Abdomen.
AB  - Recently, the Food and Drug Administration approved the use of the Orbera balloon
      for obesity treatment. However, the Food and Drug Administration later issued a
      warning about the possibility of 2 complications not previously reported: acute
      pancreatitis and balloon hyperinsufflation. This case report is intended to alert
      all clinicians that, although rare, cases of hyperinsufflation should be
      considered in patients with an intragastric balloon (IGB) and acute abdomen. IGB
      removal will resolve the complaints, provided there is no irreversible ischemia
      of the stomach walls. Care should be taken with respect to an increased risk of
      pulmonary aspiration at the time of balloon removal, and endotracheal intubation
      is highly recommended.

PMID- 30280110
TI  - Multiple Hepatic Abscess from Parvimonas micra: An Emerging Gastrointestinal
      Microbe.
AB  - Parvimonas micra is an obligate anaerobic bacterium and a known commensal of the
      human oral cavity and gastrointestinal tract. It is rarely associated with
      infections outside the oral cavity. Recently it has been isolated as a causative
      agent in a variety of systemic infections, but it has never been previously
      identified to cause a hepatic abscess. We report a 90-year-old woman with
      multiple hepatic abscesses caused by P. micra.

PMID- 30280111
TI  - Barium Enema for Treatment for Diverticular Bleeding.
AB  - Diverticula of the colon are the most common cause of lower gastrointestinal
      bleeding in adults. In cases of persistent loss of blood or severe acute
      hemorrhage, treatment is required. However, if these modern intervention
      techniques are inadequate, surgical resection of the colon may be required.
      Diverticular bleeding often concerns patients with a high surgical risk, so a
      less invasive treatment is preferable. A forgotten but excellent treatment,
      namely that of the obsolete barium contrast enema to staunch diverticular
      bleeding, is the focus of this case series. We describe 3 patients who were
      successfully treated with barium enema.

PMID- 30280112
TI  - The prevalence of malnutrition based on anthropometry among primary
      schoolchildren in Binh Dinh province, Vietnam in 2016.
AB  - Objective: The study was conducted to determine the prevalence of malnutrition
      based on anthropometry among primary schoolchildren in Binh Dinh province,
      Vietnam. Material and Methods: This was a school-based cross-sectional survey
      using random sample technique with multistage process. Variables in malnutrition
      were classifed as thinness, stunting, underweight, overweight, and obesity based
      on z-scores according to the World Health Organization (WHO) (2007).
      Anthropometric measurements were taken according to WHO's standard procedures.
      The Chi-square test was used to compare prevalences and the Chi-square test for
      trend was employed to assess the trend of the prevalence of malnutrition forms by
      age. Results: 6,514 pupils from 6 to 10 years old including 3,298 males and 3,216
      females were observed. The prevalence of thinness, stunting, underweight,
      overweight and obesity among schoolchildren accounted for 11.19%, 6.16%, 10.79%,
      and 30.1%, respectively. The prevalence of underweight and that of overweight
      obesity of all pupils at the age of 6 were 13.1% and 32.11%, respectively, and
      tended to decrease to age 10 (p < 0.01). The prevalence of thin and stunted
      pupils had little sign of change over ages (p > 0.05). There was a statistically
      significant difference in the prevalence of malnutrition in three areas of Binh
      Dinh (p < 0.05), in which the highest prevalence of undernutrition was in
      mountainous area and midland, and the highest prevalence of overweight-obesity
      was in urban areas. Conclusion: The prevalence of malnutrition of primary
      schoolchildren in Binh Dinh was relatively high, in which the prevalence of
      overweight-obesity was rather high in urban areas and the prevalence of
      undernutrition was pretty high in mountainous area and midland. This study has
      characterized an important public health challenge, highlighting the need for
      attention to potential interventions.

PMID- 30280113
TI  - Emergency department performances during overcrowding: the experience of the
      health protection agency of Brianza.
AB  - Background: Hospital emergency departments (ED) can contribute to improve health
      outcomes and reduce costs of health care system. This study evaluated ED
      admissions during a twelve months period, analyzing characteristics of patients
      who underwent to emergency care in order to understand factors involved in ED
      overcrowding and promote adequate management. Methods: This retrospective study
      analyzed a twelve months window, with in-depth focus on December/January when
      almost all EDs reported overcrowding. All ED admissions were recorded in
      electronic schedules including: demographic characteristics, time/date of the
      access, incoming triage code, diagnosis, performed procedures, discharge,
      time/date of discharge. A backward multivariable logistic regression model was
      used to estimate relationships between investigated variables and ED pattern
      mortality. Results: A total of 416,299 ED admissions were analyzed. During the
      overcrowded period there was an increase in patients admissions (+32 patients per
      day, p = 0.0079) with a statistically significant rise of critical patients
      (+1.7% yellow codes and +0.7% red codes, p < 0.001) and older subjects (+1.4%
      patients aged 75 or more years, p < 0.001). Moreover, there were statistically
      significant increases in waiting times and in length of visits, a higher
      percentage of patients who were hospitalized (13.3% vs. 12.2%, p < 0.001), left
      ED (4.46% vs. 4.15%, p < 0.001) and died (0.27% vs. 0.17%, p < 0.0001). This
      latter result maintained a marginal statistical significance (OR = 1.16, 95% CI =
      0.98-1.38, p = 0.075) after adjustment for confounding. Conclusion: Our study
      highlights that ED crowding can determine measurable worsening in ED services and
      patient outcomes as mortality, waiting times, lengths of stay, percentage of
      abandonment without being seen and, probably, costs. Thus, address ED crowding
      has to be considered an important public health priority requiring policymakers
      involvement.

PMID- 30280114
TI  - Impact of online, video-based wellness training on Girl Scout leaders' wellness
      promotion self-efficacy, intention, and knowledge: A pilot randomized controlled
      trial.
AB  - Objective: To examine the effectiveness of tailored, online, video-based training
      on Girl Scout troop leaders' wellness promotion self-efficacy, intention, and
      knowledge regarding physical activity and fruit and vegetable practices during
      troop meetings. Design: Randomized controlled trial. Methods: Thirty Girl Scouts
      leaders were randomized to control (CON; n = 16) or intervention (INT; n = 14)
      conditions. INT leaders received six online weekly training videos on
      implementation of physical activity (PA) and fruit and vegetable (FV) practices
      during troop meetings. Videos addressed leader-identified improvement areas and
      strategies to overcome barriers. Leaders set PA and FV goals for upcoming
      meetings and self-monitored their progress. Questionnaires were completed at
      baseline and post-intervention on leaders' task and barrier self-efficacy,
      intention, and knowledge regarding meeting-time PA and FV practices. Results: INT
      leaders increased PA practices barrier self-efficacy (INT = 16.5 +/- 24.1%, CON =
      -4.8 +/- 21.5%; p = 0.036), vegetable practices self-efficacy (INT = 10.3 +/-
      13.3%, CON = -3.5 +/- 28.9%; p = 0.049), and FV practices barrier self-efficacy
      (INT = 12.4 +/- 4.6%, CON = 1.6 +/- 28.7%; p = 0.036), when compared to CON
      leaders. There were no changes (p > 0.05) in PA or FV knowledge. Conclusions and
      implications: Results suggest the potential for using online video-based training
      for improvements in wellness-promoting practices of Girl Scout troop leaders.

PMID- 30280115
TI  - Criterion scores, construct validity and reliability of a web-based instrument to
      assess physiotherapists' clinical reasoning focused on behaviour change:
      'Reasoning 4 Change'.
AB  - Background and aim: 'Reasoning 4 Change' (R4C) is a newly developed instrument,
      including four domains (D1-D4), to assess clinical practitioners' and students'
      clinical reasoning with a focus on clients' behaviour change in a physiotherapy
      context. To establish its use in education and research, its psychometric
      properties needed to be evaluated. The aim of the study was to generate criterion
      scores and evaluate the reliability and construct validity of a web-based version
      of the R4C instrument. Methods: Fourteen physiotherapy experts and 39 final-year
      physiotherapy students completed the R4C instrument and the Pain Attitudes and
      Beliefs Scale for Physiotherapists (PABS-PT). Twelve experts and 17 students
      completed the R4C instrument on a second occasion. The R4C instrument was
      evaluated with regard to: internal consistency (five subscales of D1); test
      retest reliability (D1-D4); inter-rater reliability (D2-D4); and construct
      validity in terms of convergent validity (D1.4, D2, D4). Criterion scores were
      generated based on the experts' responses to identify the scores of qualified
      practitioners' clinical reasoning abilities. Results: For the expert and student
      samples, the analyses demonstrated satisfactory internal consistency (alpha
      range: 0.67-0.91), satisfactory test-retest reliability (ICC range: 0.46-0.94)
      except for D3 for the experts and D4 for the students. The inter-rater
      reliability demonstrated excellent agreement within the expert group (ICC range:
      0.94-1.0). The correlations between the R4C instrument and PABS-PT (r range: 0.06
      0.76) supported acceptable construct validity. Conclusions: The web-based R4C
      instrument shows satisfactory psychometric properties and could be useful in
      education and research. The use of the instrument may contribute to a deeper
      understanding of physiotherapists' and students' clinical reasoning, valuable for
      curriculum development and improvements of competencies in clinical reasoning
      related to clients' behavioural change.

PMID- 30280117
TI  - Behavioral risk factor clusters among university students at nine universities in
      Libya.
AB  - Objectives: This study identifies and describes the clustering of 5 behavioral
      risk factors (BRFs) among university students. We also investigated whether
      cluster membership is associated with the students' self-rated academic
      performance and self-rated health. Material and methods: A sample of 1300
      undergraduates at 6 universities and 3 colleges in Libya completed a self
      administered questionnaire that assessed BRFs (nutrition, physical activity,
      alcohol consumption, smoking, illicit drug use, inadequate sleep). A two-step
      cluster analysis generated student clusters with similar lifestyles. Results: Two
      contrasting clusters of almost even size emerged (after exclusion of alcohol and
      illicit drug use due to very low prevalence). Cluster 1 comprised students with
      higher engagement in all forms of physical activity, higher levels of health
      consciousness, greater daily fruit/vegetable intake and better sleep patterns
      than students in cluster 2. Only as regards the consumption of sweets, cluster 1
      students had less favorable practices than cluster 2 students. The prevalence of
      smoking was equally low in both clusters. Students in cluster 2, depicting a less
      healthy lifestyle, were characterized by a higher proportion of women, of
      students with less income and of higher years of study. Belonging to cluster 2
      was associated with lower self-rated health (OR: 0.46, p < 0.001) and with lower
      self-rated academic performance (OR: 0.66, p < 0.001). Conclusion: Preventive
      programs should not address BRFs in isolation and should particularly target
      students with clustering of BRFs using specifically tailored approaches.

PMID- 30280119
TI  - Assessment of levels of awareness towards blood donation in Saudi Arabia.
AB  - Background: blood products is an interesting term as all blood and blood
      transfusion procedures carry risk even with advance screening of donors and
      donated blood. In Saudi Arabia voluntary donors are either the only source or
      not, the other source is paid donors and the lack of volunteers represents a
      major challenge. This is usually attributed to low community awareness regarding
      voluntary blood donation. Therefore, the objective of this study was to assess
      the levels of awareness towards blood donation in northern Saudi Arabia.
      Methodology: in this descriptive cross sectional survey, data about blood
      donation were obtained from 717 Saudi volunteers living in the city of Hail,
      Saudi Arabia. A Purposeful questionnaire was designed and used for obtaining of
      the necessary data. Results: When asking the participants to rate the level of
      awareness about blood donation in Saudi Society, the majority of participants
      categorized the levels as good followed by very good and poor, representing
      48.8%, 29.3%, and 22% participants, respectively. Conclusion: the broad concept
      of blood donation is still poor in Saudi Arabia. Further educational plans are
      needed to raise the level of awareness and increase the perception of blood
      donation among Saudi population. Efforts should be made to involve females in
      blood donation duties.

PMID- 30280116
TI  - Review of the prevalence of postnatal depression across cultures.
AB  - The purpose of this review was to examine articles related to recent
      epidemiological evidence of the prevalence of maternal postnatal depression (PND)
      across different countries and cultures and to identify specific epidemiological
      studies that have been carried out exclusively in Malaysia on the prevalence of
      maternal PND. The review was undertaken in two stages, an initial review and an
      updated review. At both stages systematic literature searches of online databases
      were performed to identify articles on the prevalence of maternal PND. A total of
      124 articles concerning research conducted in more than 50 countries were
      included in the final analysis. There were wide variations in the screening
      instruments and diagnostic tools used although the Edinburgh Postnatal Depression
      Scale (EPDS) was the most common instrument applied to identify PND. The
      prevalence of maternal PND ranged from 4.0% to 63.9%, with Japan and America
      recording the lowest and highest rates, respectively. Within continents, a wide
      variation in reported prevalence was also found. The reported rates of maternal
      PND in Malaysia were much higher than that previously documented with a range of
      6.8-27.3%. This review indicated that the widely cited prevalence of maternal PND
      of 10-15% underestimates rates of PND worldwide. The reasons for this variability
      may not be fully explained by review methods. Future studies should evaluate the
      nature of women's PND experiences across cultures to explain these wide
      variations.

PMID- 30280120
TI  - A Qualitative Study of the Real-world Experiences of Infectious Diseases Fellows
      Regarding Antibiotic Stewardship.
AB  - Background: Antibiotic-resistant bacterial infections are a major threat to
      public health, yet improper use of antibiotics remains high. Infectious Diseases
      (ID) fellows play a major role in antibiotic stewardship efforts, but there is
      little research on how they view stewardship activities. We performed a
      qualitative study to explore ID fellows' experiences and perspectives regarding
      their antibiotic stewardship training and their role as future antibiotic
      stewards. Methods: We conducted 17 in-depth interviews with ID fellows across the
      country. The interviews were transcribed verbatim by the study team, and we used
      grounded theory to generate themes from these interviews. Results: Fellows
      focused on concrete tasks of stewardship such as performing antibiotic approvals,
      didactic and case-based education, and interactions with other physicians and
      pharmacists. There was little focus on the broader public health relevance of
      antibiotic stewardship. Pharmacists, not ID physician leaders, were identified as
      fellows' primary resource for antibiotic teaching. Several fellows suggested that
      stewardship programs should be led by pharmacists. Conclusions: ID fellowship
      training is not successfully conveying the public health importance of antibiotic
      stewardship or the role of ID physicians as leaders of antibiotic stewardship
      programs. Fellows are more focused on concrete tasks related to stewardship. ID
      training programs and societies should consider developing robust curricula
      involving fellows in the operation of the stewardship program itself, not solely
      in antibiotic approvals, emphasizing aspects of the program such as complex
      problem solving that fellows find most compelling, and emphasizing the important
      role these programs serve in improving public health.

PMID- 30280118
TI  - Paternal race/ethnicity and risk of adverse birth outcomes in the United States,
      1989-2013.
AB  - Objectives: Investigate adverse birth outcomes in the United States (US) from
      1989-2013 in relation to paternal and maternal race/ethnicity. Design: We used US
      natality data for singleton births to women 15-44 with information on
      birthweight, gestational age, and covariates (n = 90,771,339). We calculated
      unadjusted and adjusted probabilities of preterm birth (PTB, < 37 weeks
      gestation) and small for gestational age (SGA, < 10th percentile) among all
      combinations of maternal and paternal race/ethnicity: non-Hispanic black (NHB),
      non-Hispanic white (NHW), Hispanic, and Asian, and where paternal race/ethnicity
      was missing. Results: Missing, followed by NHB, paternal race/ethnicity had the
      two highest risks of PTB within each maternal racial/ethnic group. Asian,
      followed by NHW, paternal race/ethnicity had the two lowest risks of PTB. For
      SGA, however, Asian, followed by missing, paternal race/ethnicity had the two
      highest risks, and NHW race/ethnicity had the lowest risk. Our findings also
      demonstrate effect modification on the additive scale, with missing and NHB
      paternal race/ethnicity conferring a larger increase in risk of PTB for NHB women
      compared to women of other race/ethnicity groups. Conclusions: These data confirm
      US disparities in adverse birth outcomes by maternal and paternal race/ethnicity
      and argue for increased resources and interventions in response.

PMID- 30280122
TI  - Alternative REST Splicing Underappreciated.

PMID- 30280121
TI  - Characterizing the Short-Term Habituation of Event-Related Evoked Potentials.
AB  - Fast-rising sensory events evoke a series of functionally heterogeneous event
      related potentials (ERPs). Stimulus repetition at 1 Hz induces a strong
      habituation of the largest ERP responses, the vertex waves (VWs). VWs are
      elicited by stimuli regardless of their modality, provided that they are salient
      and behaviorally relevant. In contrast, the effect of stimulus repetition on the
      earlier sensory components of ERPs has been less explored, and the few existing
      results are inconsistent. To characterize how the different ERP waves habituate
      over time, we recorded the responses elicited by 60 identical somatosensory
      stimuli (activating either non-nociceptive Abeta or nociceptive Adelta
      afferents), delivered at 1 Hz to healthy human participants. We show that the
      well-described spatiotemporal sequence of lateralized and vertex ERP components
      elicited by the first stimulus of the series is largely preserved in the smaller
      amplitude, habituated response elicited by the last stimuli of the series. We
      also found that the earlier lateralized sensory wave habituates across the 60
      trials following the same decay function of the VWs: this decay function is
      characterized by a large drop at the first stimulus repetition followed by
      smaller decreases at subsequent repetitions. Interestingly, the same decay
      functions described the habituation of ERPs elicited by repeated non-nociceptive
      and nociceptive stimuli. This study provides a neurophysiological
      characterization of the effect of prolonged and repeated stimulation on the main
      components of somatosensory ERPs. It also demonstrates that both lateralized
      waves and VWs are obligatory components of ERPs elicited by non-nociceptive and
      nociceptive stimuli.

PMID- 30280123
TI  - Tackling the Social Determinants of Health: A Critical Component of Safe and
      Effective Healthcare.

PMID- 30280124
TI  - There's an App for That; Improving Communication during Pediatric Cardiothoracic
      Surgery.
AB  - Introduction: Waiting while a loved one is in surgery can be a very stressful
      time. Current processes for updating families vary from institution to
      institution. Providing timely and relevant updates, while important to the
      family, may strain a surgical team's operational system. In our initial
      experience with the Electronic Access for Surgical Events (EASE) application
      (app), we tested the extent to which its implementation improved communication
      with patient families. Methods: We compared compliance data collected pre-EASE
      (December 2013 through September 2014) and post-EASE implementation (October 2014
      until December 2015). Results: Although the pre-EASE compliance rate for bi
      hourly updates was 46% (118/255) of cases, post-EASE implementation achieved a
      compliance rate of 97% (171/176). A 2-sample test of proportions confirmed a
      significant improvement in compliance after the introduction of EASE technology
      (P < 0.001). Analysis of the 177 noncompliant cases in the pre-EASE period
      indicated that noncompliance occurred most frequently at the end of the case
      (97/177, 55%) when the patient remained in the operating room > 2 hours after the
      last update to the family. We also observed noncompliance at the beginning of the
      case (46/177, 26%), when the patient arrived in the operating room > 2 hours
      before the time of the first update. Family satisfaction scores that rated their
      experience during surgery as "Very Good" improved from 80% pre-EASE
      implementation to 97% postimplementation. We sustained this improvement for 1
      year. Conclusions: A mobile technology app (EASE) improved both frequency and
      compliance with surgical updates to families, which resulted in a statistically
      significant increase in family satisfaction scores.

PMID- 30280125
TI  - The Effect of Operating Room Temperature on the Performance of Clinical and
      Cognitive Tasks.
AB  - Introduction: Operating room (OR) temperature may impact the performance of
      health care providers. This study assesses whether hot or cold room temperature
      diminishes the performance of OR personnel measured by psychomotor vigilance
      testing (PVT) and self-report scales. Methods: This prospective observational
      study enrolled surgical/anesthesia trainees, student registered nurse
      anesthetists, and certified registered nurse anesthetists. Each provider
      participated in a test of psychomotor function and a questionnaire using a self
      report scale of personal comfort and well-being. The PVT and questionnaires were
      completed after 30 minutes of exposure to 3 different conditions (temperature of
      21 degrees C, 23 degrees C, and 26 degrees C). Results: The cohort of 22
      personnel included 9 certified registered nurse anesthetists, 7
      anesthesia/surgical trainees, and 6 student registered nurse anesthetists. Mean
      reaction time on the PVT was comparable among baseline (280 +/- 47 ms), hot (286
      +/- 55 ms; P = 0.171), and cold (303 +/- 114 ms; P = 0.378) conditions. On the
      self-report score (range, 1-21), there was no difference in the self-rated
      subjective performance between baseline and cold conditions. However, the self
      rated subjective performance scale was lower (12 +/- 6, P = 0.003) during hot
      conditions. Discussion: No difference was noted in reaction time depending on the
      temperature; however, excessive heat in the OR environment was associated with
      worse self-rated subjective performance among health care providers.
      Particularly, self-rated subjective physical demand and frustration were greater
      under hot condition.

PMID- 30280128
TI  - Erratum: Standardized Note Templates Improve Electronic Medical Record
      Documentation of Neurovascular Examinations for Pediatric Supracondylar Humeral
      Fractures.

PMID- 30280126
TI  - 10,000 Good Catches: Increasing Safety Event Reporting In A Pediatric Health Care
      System.
AB  - Background: In 2014, Children's National Health System's executive leadership
      team challenged the organization to double the number of voluntary safety event
      reports submitted over a 3-year period; the intent was to increase reliability
      and promote our safety culture by hardwiring employee event reporting. Methods:
      Following a Donabedian quality improvement framework of structure, process, and
      outcomes, a multidisciplinary team was formed and areas for improvement were
      identified. The multidisciplinary team focused on 3 major areas: the perceived
      ease of reporting (ie, how difficult is it to report an event?); the perceived
      safety of reporting (ie, will I get in trouble for reporting?); and the perceived
      impact of reporting (ie, does my report make a difference?) technology, making it
      safe to report, and how reporting makes a difference. The team developed a key
      driver diagram and implemented interventions designed to impact the key drivers
      and to increase reporting. Results: Children's National increased the number of
      safety event reports from 4,668 in fiscal year 2014 to 10,971 safety event
      reports in fiscal year 2017. Median event report submission time was decreased by
      nearly 30%, anonymous reporting decreased by 69%, the number of submitting
      departments increased by 94%, and the number of reports submitted as "other"
      decreased from a baseline of 6% to 2%. Conclusions: Children's National Health
      System's focus on increasing safety event reporting resulted in increased
      organizational engagement and attention. This initiative served as a tangible
      step to improve organizational reliability and the culture of safety and is
      readily generalizable to other hospitals.

PMID- 30280127
TI  - Impact of a Hands-free Wireless Communication Device on Communication and
      Clinical Outcomes in a Pediatric Intensive Care.
AB  - Introduction: Timely communication is essential in the intensive care
      environment. Delays may occur if communication relies on identification of
      individuals through line of sight, or use of telephones and pagers. We measured
      communication delays, staff perceptions, and clinical outcomes before and after
      implementation of a hands-free wireless communication device (HWCD) in a
      pediatric intensive care unit (PICU). Methods: Single-center study comprising 3
      components: observational study of verbal communication among PICU staff; staff
      survey regarding perceptions of communication delays; analysis of clinical data
      (length of stay, risk adjusted mortality, emergency events). All components were
      conducted before and after implementation of the HWCD. Results: Four hundred
      sixteen hours of staff working time were observed (210 pre- and 206
      postimplementation). These data showed significant reduction in communication
      delays-most notably among roaming staff [median time to response to verbal
      queries before and after implementation 120 seconds (interquartile range, 6-255)
      and 9 seconds (interquartile range, 7-30), respectively: P < 0.001]. The results
      of the staff survey showed significant improvements in staff perceptions of
      communication delays in all roaming staff groups utilizing the HWCD. The survey
      response rate was 205/361: 56.8%. There were no differences in clinical outcomes
      from the routinely collected clinical data. There was a significant reduction in
      emergency event rate-emergency summoning of assistance to bedside (per 100 bed
      days)-before and after implementation, 2.17 and 1.69, respectively: rate ratio =
      0.78 (95% confidence interval, 0.63-0.95; P < 0.05). Conclusions: Implementation
      of a HWCD was associated with significant reduction in communication delays among
      roaming staff members in PICU.

PMID- 30280129
TI  - Essential Amino Acid Supplementation Mitigates Muscle Atrophy After Total Knee
      Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial.
AB  - Background: Substantial muscle atrophy occurs after total knee arthroplasty
      (TKA), resulting in decreased strength and impaired mobility. We sought to
      determine whether perioperative supplementation with essential amino acids (EAA)
      would attenuate muscle atrophy following TKA and whether the supplements were
      safe for ingestion in an older surgical population. Methods: We performed a
      double-blind, placebo-controlled, randomized trial of 39 adults (age range, 53 to
      76 years) undergoing primary unilateral TKA who ingested 20 g of EAA (n = 19) or
      placebo (n = 20) twice daily for 7 days preoperatively and for 6 weeks
      postoperatively. At baseline and 6 weeks postoperatively, magnetic resonance
      imaging (MRI) scans were obtained to measure quadriceps and hamstrings muscle
      volume. Secondary outcomes included functional mobility and strength. Data on
      physical activity, diet, and patient-reported outcomes (Veterans RAND 12-Item
      Health Survey and Knee injury and Osteoarthritis Outcome Score) were collected.
      Safety was determined through blood tests evaluating blood urea nitrogen,
      creatinine, creatinine clearance, homocysteine, and renal and liver function.
      Laboratory values at baseline, on the day of surgery, and at 2 days, 2 weeks, and
      6 weeks postoperatively were compared between treatment groups. Analysis of
      covariance models, with baseline values as covariates, were used to evaluate
      outcomes between treatment groups. P values were adjusted for multiple tests.
      Results: Compared with baseline, the EAA group had significantly less decrease in
      mean quadriceps muscle volume compared with the placebo group in the involved leg
      (-8.5% +/- 2.5% compared with -13.4% +/- 1.9%; p = 0.033) and the contralateral
      leg (-1.5% +/- 1.6% compared with -7.2% +/- 1.4%; p = 0.014). The hamstrings also
      demonstrated a greater muscle-volume-sparing effect for the EAA group than for
      the placebo group in the involved leg (-7.4% +/- 2.0% compared with -12.2% +/-
      1.4%; p = 0.036) and contralateral leg (-2.1% +/- 1.3% compared with -7.5% +/-
      1.5%; p = 0.005). There were no differences between the groups in terms of
      functional measures or strength. Blood chemistry values varied significantly
      between assessments periods but did not statistically differ between groups.
      Conclusions: The results of the present study suggest that EAA supplementation is
      safe and reduces the loss of muscle volume in older adults recovering from TKA.
      Level of Evidence: Therapeutic Level II. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 30280130
TI  - Patients at the Highest Risk for Reherniation Following Lumbar Discectomy in a
      Multicenter Randomized Controlled Trial.
AB  - Background: The purposes of the present study were to (1) confirm the risk of
      recurrent lumbar disc herniation in patients with a large anular defect who had
      undergone limited discectomy and (2) assess potential risk factors within this
      population. Methods: The patient population was extracted from the control cohort
      of a prospective, randomized, multicenter controlled trial investigating the
      efficacy of an anular closure device following standard limited discectomy. All
      control patients underwent limited discectomy for the treatment of a single-level
      symptomatic posterior or posterolateral lumbar disc herniation. Only patients
      presenting with a large anular defect (6 to 10 mm wide by 4 to 6 mm long) were
      included in the study (n = 278). Baseline demographic, clinical, and surgical
      characteristics were recorded. Follow-up evaluations were performed at 6 weeks
      and at 3, 6, 12, and 24 months. Imaging modalities included magnetic resonance
      imaging, low-dose computed tomography, and radiographs. Symptomatic recurrent
      lumbar disc herniation was defined as any symptomatic postoperative herniation on
      either side of the index level. A multivariate logistic regression analysis of
      demographic and surgical variables associated with the incidence of recurrent
      lumbar disc herniation was performed. Results: The mean anular defect area (and
      standard deviation) was 39.3 +/- 9.1 mm2, and the mean excised nuclear tissue
      volume was 1.3 +/- 0.8 mL. At 2 years, the incidence of symptomatic recurrent
      lumbar disc herniation was 25.3% (64 of 253), with the herniation occurring at a
      mean of 264 days after the index procedure. Of the 64 patients with recurrent
      lumbar disc herniation, 36 underwent a subsequent surgical procedure. Logistic
      regression analysis identified an increased risk for recurrent lumbar disc
      herniation in females (odds ratio, 2.2) and in patients with greater anular
      defect widths (odds ratio, 1.3). Furthermore, multivariate logistic regression
      analyses revealed a significant interaction between age and sex (p = 0.005).
      Conclusions: The outcomes of the present study provide the most substantial
      evidence to date in confirming previous reports of a high risk of reherniation
      among patients with large anular defects. Among those with large anular defects
      (width, >=6 mm), females <=50 years of age had the highest risk (up to ~10 times
      higher) of recurrent lumbar disc herniation. It is recommended that an anular
      repair or closure should be performed after limited discectomies in patients with
      large anular defects. Level of Evidence: Therapeutic Level IV. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 30280131
TI  - Incidence and Characterization of Major Upper-Extremity Amputations in the
      National Trauma Data Bank.
AB  - Background: There are few recent data examining the epidemiology of severe upper
      extremity trauma in non-military patients. We used the National Trauma Data Bank
      (NTDB) to investigate the epidemiology and descriptive characteristics of upper
      extremity amputations in U.S. trauma centers. Methods: We queried the 2009 to
      2012 NTDB research datasets for patients undergoing major upper-extremity
      amputation and extracted characteristics of the patient population, injury
      distribution, and treating facilities. In addition, multivariable regression
      models were fit to identify correlates of reoperation, major in-hospital
      complications, duration of hospitalization, and in-hospital mortality. Results: A
      total of 1,386 patients underwent a major upper-extremity amputation secondary to
      a trauma-related upper-extremity injury, representing 46 per 100,000 NTDB trauma
      admissions from 2009 to 2012. The most frequent definitive procedures performed
      were amputations through the humerus (35%), forearm (30%), and hand (14%). The
      average duration of hospitalization for all amputees was 17 days. Thirty-one
      percent of patients underwent at least 1 reoperation. The rate of reoperation was
      significantly higher at university-associated hospitals compared with nonteaching
      or community hospitals (p < 0.0001). Patients who had at least 1 reoperation
      stayed in the hospital approximately 7 days longer than patients who did not
      undergo reoperation. The Injury Severity Score, hospital teaching status,
      concomitant neurovascular injury, and occurrence of a complication were
      significantly associated with reoperation. Conclusions: The present study
      provides an updated report on the epidemiology and characteristics of trauma
      related major upper-extremity amputation in the U.S. civilian population.
      Additional work is necessary to assess the long-term outcomes following attempted
      upper-extremity salvage. The population-level data provided by the present study
      may help to inform the design and implementation of future studies on the optimum
      treatment for this survivable but life-altering injury.

PMID- 30280132
TI  - The Effect of Age, Sex, Area Deprivation, and Living Arrangements on Total Knee
      Replacement Outcomes: A Study Involving the United Kingdom National Joint
      Registry Dataset.
AB  - Background: Total knee replacement (TKR) is a common procedure for the treatment
      of osteoarthritis that provides a substantial reduction of knee pain and improved
      function in most patients. We investigated whether sociodemographic factors could
      explain variations in the benefit resulting from TKR. Methods: Data were
      collected from 3 sources: the National Joint Registry for England, Wales,
      Northern Ireland, and the Isle of Man; National Health Service (NHS) England
      Patient Reported Outcome Measures; and Hospital Episode Statistics. These 3
      sources were linked for analysis. Pain and function of the knee were measured
      with use of the Oxford Knee Score (OKS). The risk factors of interest were age
      group, sex, deprivation, and social support. The outcomes of interest were
      sociodemographic differences in preoperative scores, 6-month postoperative
      scores, and change in scores. Results: Ninety-one thousand nine hundred and
      thirty-six adults underwent primary TKR for the treatment of osteoarthritis in an
      NHS England unit from 2009 to 2012. Sixty-six thousand seven hundred and sixty
      nine of those patients had complete knee score data and were included in the
      analyses for the present study. The preoperative knee scores were worst in female
      patients, younger patients, and patients from deprived areas. At 6 months
      postoperatively, the mean knee score had improved by 15.2 points. There were
      small sociodemographic differences in the benefit of surgery, with greater area
      deprivation (-0.71 per quintile of increase in deprivation; 95% confidence
      interval [CI], -0.76 to -0.66; p < 0.001) and younger age group (-3.51 for <=50
      years compared with 66 to 75 years; 95% CI, -4.00 to -3.02; p < 0.001) associated
      with less benefit. Cumulatively, sociodemographic factors explained <1% of the
      total variability in improvement. Conclusions: Sociodemographic factors have a
      small influence on the benefit resulting from TKR. However, as they are
      associated with the clinical threshold at which the procedure is performed, they
      do affect the eventual outcomes of TKR. Level of Evidence: Prognostic Level IV.
      See Instructions for Authors for a complete description of evidence.

PMID- 30280133
TI  - Treatment of Brachymetatarsia Involving the Great Toe.
AB  - Background: Brachymetatarsia is usually treated by lengthening the metatarsals,
      but excessive lengthening can be associated with complications. Our technique
      combines 1-stage step-cut lengthening of the first metatarsal with shortening
      and/or lengthening of the neighboring metatarsals and/or phalanges. Methods:
      Twenty-four feet (15 patients) were treated for first-ray brachymetatarsia.
      Widely available commercial image-editing software was used to make a
      preoperative plan for each patient, with emphasis on the creation of a
      cosmetically satisfying toe-length arc with minimum shortening and lengthening of
      the affected metatarsals and proximal phalanges. Length gain and percentage
      increase were also recorded postoperatively. The American Orthopaedic Foot &
      Ankle Society (AOFAS) hallux metatarsophalangeal-interphalangeal scoring system
      was used for clinical evaluation. Results: In all 24 feet, smooth parabolas were
      created at the level of the metatarsal heads and at the toe tips. All patients
      showed osseous union, and no complications were noted. However, most patients
      showed mildly restricted range of motion of the first metatarsophalangeal joint.
      The mean AOFAS score of the hallux significantly improved from 88.3
      preoperatively to 98.1 at the latest follow-up (p < 0.001). Conclusions: One
      stage step-cut lengthening of the first metatarsal combined with shortening
      and/or lengthening of the adjacent metatarsal and phalangeal bones provides
      excellent cosmetic and functional results. Level of Evidence: Therapeutic Level
      IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 30280135
TI  - The Use of a Free Fibular Strut as a "Biological Intramedullary Nail" for the
      Treatment of Complex Nonunion of Long Bones.
AB  - Background: Nonunion of long-bone fractures is difficult to treat, especially
      when the bones are osteoporotic or there is a large bone gap as a result of
      repeated failure of the metallic nails or implants. In such cases, the use of an
      autologous intramedullary fibular strut graft may be a viable treatment option.
      Methods: Twenty-two patients with a complex nonunion of the shaft of the femur,
      humerus, or tibia were managed with a free autologous fibular strut graft for
      intramedullary fixation with use of closed or open methods. All patients had
      evidence of moderate to severe local osteoporosis and had a bone gap ranging from
      4 to 20 mm. Nineteen patients had had 1 to 4 prior operations. The mean age was
      51.5 years. The duration of nonunion ranged from 9 months to 4 years. Results:
      The mean time to union was 17 weeks (range, 8 to 26 weeks), and the mean duration
      of follow-up was 4 years (range, 6 months to 17 years). All but 2 patients had
      healing at the time of the latest follow-up. Conclusions: The identification of a
      viable option for the treatment of difficult nonunion in osteoporotic bones has
      been a challenge. The insertion of a free autologous intramedullary fibular strut
      graft provided mechanical stability, and osteogenesis occurred inside the
      medullary canal of the host bone. Level of Evidence: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30280134
TI  - Clinical Outcomes According to Femoral and Acetabular Version After
      Periacetabular Osteotomy.
AB  - Background: Patients with acetabular dysplasia often have abnormal femoral and
      acetabular version. The effect of combined femoral and acetabular version on
      clinical outcomes after periacetabular osteotomy for the treatment of acetabular
      dysplasia remains unclear. The purposes of the present study were (1) to evaluate
      the association of combined femoral and acetabular version with clinical outcome
      after periacetabular osteotomy and (2) to investigate the association of femoral
      version independently with clinical outcome after periacetabular osteotomy.
      Methods: We retrospectively reviewed the records for 92 consecutive patients (95
      hips) who had undergone periacetabular osteotomy for the treatment of symptomatic
      acetabular dysplasia. The patient cohort comprised 85 females and 7 males with a
      mean age of 38.9 years at the time of surgery. The mean duration of follow-up was
      4.8 years (range, 2.0 to 7.2 years). Femoral and acetabular version and the alpha
      angle were measured on postoperative computed tomography scans. Clinical outcomes
      included range of motion and the modified Harris hip score. Analysis of variance
      was used to investigate the effect of femoral version on clinical outcomes.
      Analysis of covariance was used to adjust for potential covariates. Results:
      Combined femoral and acetabular version after periacetabular osteotomy was
      slightly, but significantly, correlated with postoperative flexion (r = 0.222; p
      = 0.031) and internal rotation in flexion (r = 0.326; p = 0.001). Patients with
      mild femoral version (<15 degrees ) experienced significantly less postoperative
      internal rotation in flexion than those with severe femoral version (>35 degrees
      ); however, this difference was lost after adjustment for potential covariates.
      There were no differences among femoral version groups (mild, moderate, and
      severe) in terms of improvements in the clinical outcomes of pain, function, and
      activity. Conclusions: Combined femoral and acetabular version after
      periacetabular osteotomy was significantly correlated with postoperative range of
      motion. Abnormality of femoral version associated with acetabular dysplasia did
      not demonstrate any effect on the clinical outcomes of periacetabular osteotomy.
      Level of Evidence: Prognostic Level IV. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 30280136
TI  - Patient Profiling Can Identify Spondylolisthesis Patients at Risk for Conversion
      from Nonoperative to Operative Treatment.
AB  - Background: Factors that are relevant to the decision regarding the use of
      surgical treatment for degenerative spondylolisthesis include disease-state
      severity and patient quality-of-life expectations. Some factors may not be easily
      appraised by the surgeon. In prospective trials involving patients undergoing
      nonoperative and operative treatment, there are instances of crossover in which
      patients from the nonoperative group undergo surgery. Identifying and
      understanding patient characteristics that may influence crossover from
      nonoperative to operative treatment will aid understanding of what motivates
      patients toward pursuing surgery. Methods: Patients with degenerative
      spondylolisthesis who were randomized to nonoperative care in a prospective,
      multicenter study were evaluated over 8 years of enrollment. Two cohorts were
      defined: (1) the surgery cohort (patients who underwent surgery at any point) and
      (2) the nonoperative cohort (patients who did not undergo surgery). A Cox
      proportional hazards model, modeling time to surgery, was used to explore
      demographic data, clinical diagnoses, and patient expectations and attitudes
      after adjusting for other variables. A subanalysis was performed on surgery
      within 6 months after enrollment and surgery >6 months after enrollment. Results:
      One hundred and forty-five patients who had been randomized to nonoperative
      treatment, 80 of whom crossed over to surgery, were included. In analyzing
      baseline differences between the 2 cohorts, patients who underwent surgery were
      younger; however, there were no significant difference between the cohorts in
      terms of race, sex, or comorbidities. Treatment preference, greater Oswestry
      Disability Index score, marital status, and no joint problems were predictors of
      crossover to surgery. Clinical factors, including stenosis, neurological
      deficits, and listhesis levels, did not show a significant relationship with
      crossover. At the time of long-term follow-up, the surgery cohort showed
      significantly greater long-term improvement in health-related quality of life (p
      < 0.001). The difference was maintained throughout follow-up. Conclusions:
      Neurological symptoms and diagnoses, including listhesis and stenosis severity,
      did not predict crossover from nonoperative care to surgery. Attitudes toward
      surgery, greater Oswestry Disability Index score, marital status, and no joint
      problems were independent predictors of crossover from nonoperative to operative
      care. Certain demographic characteristics were associated with higher rates of
      crossover, although they were connected to patient attitudes toward surgery.
      Level of Evidence: Prognostic Level II. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 30280137
TI  - Restoration of External Rotation Following Reverse Shoulder Arthroplasty without
      Latissimus Dorsi Transfer.
AB  - Background: Latissimus dorsi transfers have been considered necessary to restore
      active external rotation following reverse shoulder arthroplasty (RSA). The
      purpose of this study was to assess the effectiveness of an RSA system that
      lateralizes the center of rotation in restoring active external rotation without
      a latissimus dorsi transfer in patients with a preoperative external rotation
      deficit (external rotation of <0 degrees ). Methods: We retrospectively reviewed
      the records of patients who had undergone RSA with a lateralized center of
      rotation without a latissimus dorsi transfer. All patients had had a preoperative
      external rotation deficit (active external rotation of <0 degrees ), and all were
      followed for a minimum of 2 years. Patients were stratified into 2 groups on the
      basis of the preoperative diagnosis: (1) those with a combined loss of active
      elevation and external rotation as a result of rotator cuff tear arthropathy
      (CLEER group) and (2) those with a combined loss of active elevation and external
      rotation as a result of other posttraumatic etiologies (non-CLEER group). The
      mean improvement of external rotation was analyzed. Subgroup analysis was
      performed on the basis of the Goutallier classification, glenosphere
      lateralization, and total prosthetic lateralization. Results: Thirty-three
      patients (24 in the CLEER group and 9 in the non-CLEER group) met the inclusion
      criteria. The average follow-up was 43.4 months (range, 24 to 77 months).
      External rotation improved significantly in both the CLEER group (from -21
      degrees  preoperatively to 28 degrees  postoperatively; p < 0.001) and the non
      CLEER group (from -19 degrees  preoperatively to 26 degrees  postoperatively; p =
      0.001). Goutallier classification, glenosphere lateralization, and total
      prosthetic lateralization were not correlated with the degree of improvement of
      external rotation in either group (p > 0.05 for all). Conclusions: RSA with a
      lateralized center of rotation can effectively restore external rotation without
      the use of a latissimus dorsi transfer in patients with a preoperative external
      rotation deficit as a result of rotator cuff arthropathy or other posttraumatic
      etiologies. Level of Evidence: Therapeutic Level IV. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 30280138
TI  - Characteristics of Benign and Malignant Bone Tumors Registered in the Hiroshima
      Tumor Tissue Registry, 1973-2012.
AB  - Background: Reported information on the characteristics of benign bone tumors is
      disjointed, and the long-term trends in the occurrence of malignant bone tumors
      by histological type have not been reported in Japan. Our aim was to describe the
      characteristics of both benign and malignant bone tumors as described in cases
      registered in the Hiroshima Tumor Tissue Registry from 1973 to 2012. Methods:
      Cases were identified with the International Classification of Diseases for
      Oncology (ICD-O-3) topography code C40-C41 (bones, joints, and articular
      cartilage), and histological types were classified according to the World Health
      Organization 2013 system. We described the distribution of the cases by behavior,
      sex, skeletal site of tumor occurrence, histological type, period at diagnosis
      (in 10-year groups), and age at diagnosis (in 10-year groups). Results: We
      observed 2,542 benign bone tumors, 272 intermediate bone tumors, and 506
      malignant bone tumors. We confirmed that 81.6% of benign bone tumors were
      chondrogenic, consisting primarily of osteochondromas and enchondromas. Giant
      cell tumor of bone was the most dominant type of intermediate tumor, whereas
      osteogenic tumors and chondrogenic tumors were the most dominant types of
      malignant tumors. Among malignant bone tumors, 41.7% of tumors occurred in the
      long bones of the lower limb, and there were different peaks of age at the time
      of diagnosis for osteogenic tumors and chondrogenic tumors. A similar
      distribution of histological types was seen throughout the 40-year observation
      period. Conclusions: Osteochondroma and enchondroma differed in terms of the age
      of the patient at the time of diagnosis and the skeletal sites where the tumors
      most frequently occurred. Giant cell tumor had a large impact on occurrence as a
      common type of intermediate bone tumor. Clinical Relevance: The results of the
      present study, based on pathological tissue registry data, provide knowledge
      about the epidemiological and pathological features of bone tumors in Japan.

PMID- 30280139
TI  - Fifty Most-cited Articles on Lateral Epicondylitis of the Elbow.
AB  - Introduction: Citation number can be used as a marker of a scientific article's
      influence. This study sought to determine and characterize the most-cited
      investigations on lateral epicondylitis and identify the most influential studies
      pertaining to this pathology. Methods: The Institute for Scientific Information
      Web of Science database was queried for articles investigating lateral
      epicondylitis, and the 50 most-cited articles were selected. For each article,
      number of citations, citation density, journal, publication year, country of
      origin, language, article type, article subtype, and level of evidence were
      recorded. Results: Citation numbers ranged from 72 to 332 (mean, 127.4), and
      densities ranged from 1.6 to 34.0 (mean, 9.4). Articles were published across 26
      different journals. Most articles (41) were clinical, with randomized controlled
      trials (29.3%) being the most commonly cited articles. Discussion: Compared with
      previous investigations looking at citation density within orthopaedics, the most
      commonly cited clinical articles on lateral epicondylitis had a high percentage
      of level I or II evidence (39.0%). This compilation of the literature can aid in
      establishing reading curriculums for trainees in both orthopaedic residencies and
      fellowships. This is a Level V study.

PMID- 30280140
TI  - Orthopaedic Academic Activity in the United States: Bibliometric Analysis of
      Publications by City and State.
AB  - Background: The purpose of this study was to conduct a bibliometric analysis of
      orthopaedic academic output in the United States. Methods: Publications based on
      city and state origin, corrected for population size, median household income,
      total number of surgeons, and the number of various subspecialties were
      evaluated. The 15 highest-ranked orthopaedic journals were audited from 2010 to
      2014 and then subdivided into anatomic regions and 14 subspecialties. Results: A
      total of 8,100 articles were published during the study period. Most originated
      from New York, California, Pennsylvania, Massachusetts, and Minnesota. New York
      published the greatest number by city, followed by Philadelphia, Boston, Chicago,
      and Rochester. When adjusted for the number of publications per city, surgeons
      per population, publications per surgeon population, publications per population,
      and publications per median income per capita, Vail and New York led in two and
      Stanford in one of the metrics. Conclusions: New York was the leader for the
      total publications, greatest activity within subspecialties, and publications per
      surgeon/population and per median income/capita. Vail was the leader for
      publications/surgeon and population. The top four cities of New York,
      Philadelphia, Boston, and Chicago were responsible for 28% of the academic output
      over the 5-year study period.

PMID- 30280141
TI  - A High-fidelity Tactile Hand Simulator as a Training Tool to Develop Competency
      in Percutaneous Pinning in Residents.
AB  - Introduction: We developed an economical three-dimensional printed and casted
      simulator of the hand for the training of percutaneous pinning. This simulator
      augments the traditional "See one, do one, teach one" training model. Methods: To
      evaluate the simulator, five expert orthopaedic surgeons were recruited to
      perform percutaneous pinning on the simulator and then to complete a
      questionnaire on its realism and expected usefulness. Evaluation was based on
      responses to multiple-choice questions and a Likert-type scale. Results: All
      subjects expressed that the tactile hand simulator is useful for residency
      training. They would recommend the simulator to their colleagues and indicated
      interest in testing future iterations. Subjects rated highly the realism of the
      material, the purchase of the pin, and the cortical-cancellous bone interface.
      Conclusion: The learning of tactile skills in addition to visual cues on a
      tactile simulator is expected to benefit residents. It provides a low-cost and
      low-risk environment outside the operating room for residents to hone their
      skills.

PMID- 30280142
TI  - Patient Dose Comparison for Intraoperative Imaging Devices Used in Orthopaedic
      Lumbar Spinal Surgery.
AB  - Background: The aim of this study was to determine the amount of radiation
      exposure from intraoperative imaging during two-level and four-level lumbar
      fusions. Methods: Five imaging systems were studied: multidetector CT (MDCT)
      scanner (CT A); two mobile CT units (CT B and CT C); a C-arm (D); and fluoroscopy
      (E). Metal oxide semiconductor field effect transistor dosimeters measured doses
      at 25 organ locations using an anthropomorphic phantom. A fat-equivalent phantom
      was used to simulate an obese body mass index (BMI). Results: The effective dose
      (ED) for C-arm D was estimated using commercial software. The ED for others was
      computed from the measured mean organ doses. EDs for a normal BMI patient,
      receiving a four-level fusion, are as follows: CT A (12.00 +/- 0.30 mSv), CT B
      (5.90 +/- 0.25 mSv), CT C (2.35 +/- 0.44 mSv), C-arm D (0.44 mSv), and
      fluoroscopy E (0.30 +/- 0.3 mSv). The rankings are consistent across all three
      BMI values except CT C and fluoroscopy E, which peaked in the overweight size
      because of system limitations. The other machines' ED trended with patient BMI.
      Conclusion: The dose reduction protocols were confirmed according to the
      manufacturer's specifications. The results of this study emphasize the need for
      the appropriate selection of the imaging system, especially because the type of
      device could have a substantial effect on patient radiation risk.

PMID- 30280143
TI  - Idiopathic Charcot Arthropathy of the Knee Presenting as a Bicondylar Tibial
      Plateau Fracture.
AB  - Charcot arthropathy is an infrequent condition that primarily involves the foot
      and ankle; rarely, it has been reported to affect the knee. Risk factors for
      Charcot arthropathy are well described with diabetes being the most common cause.
      Idiopathic Charcot arthropathy without a secondary etiology is extremely rare,
      with only a few cases described involving the foot and shoulder. Clinically,
      idiopathic Charcot arthropathy presents a notable challenge because delayed
      diagnosis can lead to surgical complications and advancement of joint
      destruction. We report idiopathic Charcot arthropathy of the knee presenting as a
      bicondylar tibial plateau fracture successfully managed with total knee
      arthroplasty after failed open reduction internal fixation. We diagnosed the
      patient when the clinical/surgical presentation was indicative of Charcot
      arthropathy and after excluding all other diagnoses. This previously unreported
      case describes the complexity of idiopathic Charcot arthropathy with subsequent
      fractures and highlights the importance of patient history, presentation, and
      surgical intervention.

PMID- 30280144
TI  - Erratum: Use of Three-dimensional Printing in Orthopaedic Surgical Planning:
      Erratum.
AB  - [This corrects the article DOI: 10.1097/YIC.0000000000000215.].

PMID- 30280145
TI  - Pyogenic Sacroiliitis in a Pediatric Patient: A Rare Case of Infection by
      Streptococcus intermedius.
AB  - This is a case report of pyogenic sacroiliitis in a pediatric patient caused by
      Streptococcus intermedius. The patient is a 16-year-old boy who presented to an
      emergency department with sudden onset of back pain radiating to the left lower
      extremity. The diagnosis was confounded by the presence of isthmic
      spondylolisthesis. Plain radiography demonstrated mild isthmic spondylolisthesis
      but no radiographic signs of tumor, trauma, infection, arthritis, or other
      developmental problems. The C-reactive protein level was 23 mg/L. Over the next
      24 hours, the patient developed fever, and the C-reactive protein level increased
      to 233 mg/L. Sacroiliitis and an iliopsoas abscess were identified on MRI. Blood
      cultures grew S intermedius. The patient responded to antibiotic treatment and
      needle aspiration under CT guidance. Sacroiliitis is an uncommon condition and,
      to our knowledge, there is only one other case report of its being caused by S
      intermedius. The previous report was in an adult.

PMID- 30280147
TI  - Microbiota-accessible pectic poly- and oligosaccharides in gut health.
AB  - Diverse human intestinal microbiota are regarded as a prerequisite for a healthy
      intestine. Commercial prebiotic products have a limited ability to provide
      microbial diversity in the human gut, because they mostly comprise oligomers of
      the same monosaccharide residues and a small fraction of them can reach the
      distal colon. Therefore, the demand for diverse prebiotic ingredients and dietary
      fibers with improved functional properties is increasing tremendously. The main
      sources of carbohydrates in our diet are plant-derived polysaccharides, which are
      consumed by the bacteria present in the intestine. Among these, pectin-derived
      poly- and oligosaccharides serve as the best alternative, as they are resistant
      to human gastric juice and are fermented slowly in the large intestine to impart
      a prebiotic effect. The main components of pectin are polygalacturonic acids in
      association with neutral polysaccharides such as arabinan, arabinogalactan, and
      galactan. The present review deals with the health-related functional properties
      of pectic poly- and oligosaccharides and their applications in the food industry.
      Different mechanisms involved in the hydrolysis of these carbohydrates by the
      intestinal bacteria and in maintaining the microbial diversity of the intestine
      are also discussed. It also emphasizes the current methods for the production and
      purification of different pectins and their oligosaccharides.

PMID- 30280146
TI  - Reliability and Construct Validity of the Adapted Norwegian Version of the Early
      Onset Scoliosis 24-item Questionnaire.
AB  - Background: The Early-Onset Scoliosis 24-item Questionnaire (EOSQ-24) reflects
      issues important for patients with early-onset scoliosis (EOS) and their parents.
      The aim of this study was to translate the original EOSQ-24 into Norwegian and to
      evaluate the resulting questionnaire's reliability and construct validity.
      Methods: The EOSQ-24 was translated using a forward-backward translation method,
      followed by an expert review. One hundred parents of a heterogenic group of
      patients with EOS answered the EOSQ-24 and scored Numeric Rating Scales (NRSs) to
      evaluate the children's general health, pain, and physical function. Two weeks
      later, 55 parents (55%) answered the retest questionnaire. Data quality, internal
      consistency, and test-retest reliability were assessed, including the minimal
      detectable change. Construct validity was evaluated by predefined hypotheses and
      correlations with NRS scores. Results: There were considerable ceiling (19.0% to
      63.0%) and floor effects (zero to 26.0%). The internal consistency was excellent
      (Cronbach alpha = 0.95). The minimal detectable change for the EOSQ-24 total
      score was 15.2 and ranged from 21.6 to 33.0 for the subdomains scores. The EOSQ
      24 showed discriminate capabilities among patients with different etiology,
      treatment status, and severity of deformity. High correlations were found between
      the EOSQ-24 total score and the NRS scores for general health (r = -0.66), pain
      (r = -0.63), and physical function (r = -0.78). Conclusion: The Norwegian version
      of the EOSQ-24 has acceptable reliability and validity for measuring quality of
      life and caregiver burden among EOS children. The EOSQ-24 total score is
      acceptable for evaluation of these patients over time. Level of Evidence: Level
      III, diagnostic study.

PMID- 30280148
TI  - MOF based on a longer linear ligand: electrochemical performance, reaction
      kinetics, and use as a novel anode material for sodium-ion batteries.
AB  - A metal-organic framework based on a longer linear ligand was rationally designed
      and evaluated as a novel anode material for sodium-ion batteries. It delivered a
      high specific capacity of 269 mA h g-1 with a desired voltage plateau and
      demonstrated excellent capacity retention (79.0% after 1000 cycles). In addition,
      its reaction kinetics was also investigated in detail by performing cyclic
      voltammetry and a predominantly diffusion-controlled process was clearly
      revealed.

PMID- 30280149
TI  - Characterization of phenolic compounds in tincture of edible Nepeta nuda:
      development of antimicrobial mouthwash.
AB  - The activity of edible Nepeta nuda L. (Lamiaceae) tincture and Listerine towards
      a selected group of oral pathogenic microorganisms (4 bacterial and 9 fungal
      strains) has been explored. Their potentials to inhibit the formation of biofilm
      and to diminish established biofilm have been compared. The amount of N. nuda
      tincture and swishing time necessary for reaching better or equivalent
      antimicrobial effect than that of Listerine have been predicted. Phenolic
      compounds in N. nuda tincture are determined by LC-DAD/ESI-MSn. Both Listerine
      and N. nuda tincture possess good antimicrobial potentials (MIC in the range of
      0.8-15 MUL per well) including inhibition of biofilms. Rosmarinic acid and
      verminoside are the most dominant phenolic compounds present in the N. nuda
      tincture. Based on in vitro results, we infer that it is more desirable to swish
      20 mL of mouthwashes (Listerine and N. nuda tincture, 100 mg mL-1) for 30 s when
      dealing with selected microorganisms in general and for 60 s (N. nuda tincture)
      when dealing with bacterial biofilms.

PMID- 30280150
TI  - Polymerization led selective detection and removal of Zn2+ and Cd2+ ions:
      isolation of Zn- and Cd-MOFs and reversibility studies.
AB  - This work illustrates two post-functionalized chemosensors and their remarkable
      role in the sensing of Zn2+ and Cd2+ ions via producing the corresponding
      insoluble metal-organic frameworks (MOFs). The structural characterization of the
      resultant Zn- and Cd-MOFs revealed their polymeric one- or two-dimensional
      architectures. Importantly, nitrate and nitrite ions reversed the MOF
      polymerization process and regenerated the chemosensors and the corresponding
      metal salts. These results are significant in terms of recyclability and
      remediation processes for the removal of metals both from living organisms and
      the environment.

PMID- 30280151
TI  - Electrolyte solvents for high voltage lithium ion batteries: ion correlation and
      specific anion effects in adiponitrile.
AB  - We studied dynamic and structural properties of two lithium conducting salts in
      the aprotic organic solvent adiponitrile by a combination of atomistic molecular
      dynamics (MD) simulations, quantum chemical calculations, and experimental
      findings. The outcomes of our simulations reveal significant differences between
      both lithium salts, namely lithium tetrafluoroborate (LiBF4) and lithium
      bis(trifluoromethanesulfonyl)imide (LiTFSI) at various concentrations, which can
      be mainly attributed to the solvation behavior of the individual anions. The
      increased tendency of ion complex formation for LiBF4 is reflected by lower
      values regarding the measured and computed effective ionic conductivities when
      compared to LiTFSI. All findings highlight the crucial importance of specific
      anion effects in combination with molecular details of solvation, and advocate
      the use of adiponitrile as a beneficial solvent in modern lithium ion battery
      technology with high voltage electrodes.

PMID- 30280152
TI  - Assembled anti-adhesion polypropylene mesh with self-fixable and degradable in
      situ mussel-inspired hydrogel coating for abdominal wall defect repair.
AB  - Abdominal adhesion to polypropylene (PP) mesh remains one of the major
      complications in hernia repair. Thus, a challenge exists to endow PP mesh with
      powerful anti-adhesion properties in hernia repair. To investigate potential
      options, the assembled PP mesh was developed with effective anti-adhesion
      properties through an in situ coating of the mesh surface with self-fixable and
      biodegradable mussel-inspired hydrogels. Through mixing oxidized
      carboxymethylcellulose functionalized with dopamine (OCMC-DA) with
      carboxymethylchitosan (CMCS), a layer of hydrogel (OCMC-DA/CMCS) can be formed in
      situ on the PP mesh without the addition of crosslinking agents; the dopamine
      then acts as an immobilization group to fix these hydrogels to the PP mesh and
      the tissue surface. In this way, the assembled PP mesh (OCMC-DA/CMCS/PP) was
      obtained. The properties of the OCMC-DA/CMCS hydrogels were optimized, and the
      OCMC-DA4/CMCS hydrogel was selected to construct the assembled PP mesh. The lap
      shear test revealed that OCMC-DA4/CMCS has tissue-adhesive properties. In vitro
      cell tests proved the excellent biocompatibility of the hydrogel. An optimized
      bioabsorption time and significant anti-adhesion properties were demonstrated
      through an in vivo test with a rat model. The adhesion area and tenacity of the
      OCMC-DA4/CMCS/PP group were more than 80% lower than those of the native PP mesh
      group and created a slightly inflammatory reaction.

PMID- 30280153
TI  - Methanol as hydrogen source: transfer hydrogenation of aromatic aldehydes with a
      rhodacycle.
AB  - A cyclometalated rhodium complex has been shown to perform highly selective and
      efficient reduction of aldehydes, deriving the hydrogen from methanol. With
      methanol as both the solvent and hydrogen donor under mild conditions and an open
      atmosphere, a wide range of aromatic aldehydes were reduced to the corresponding
      alcohols, without affecting other functional groups.

PMID- 30280154
TI  - Engineering enzymes for noncanonical amino acid synthesis.
AB  - The standard proteinogenic amino acids grant access to a myriad of chemistries
      that harmonize to create life. Outside of these twenty canonical protein building
      blocks are countless noncanonical amino acids (ncAAs), either found in nature or
      created by man. Interest in ncAAs has grown as research has unveiled their
      importance as precursors to natural products and pharmaceuticals, biological
      probes, and more. Despite their broad applications, synthesis of ncAAs remains a
      challenge, as poor stereoselectivity and low functional-group compatibility
      stymie effective preparative routes. The use of enzymes has emerged as a
      versatile approach to prepare ncAAs, and nature's enzymes can be engineered to
      synthesize ncAAs more efficiently and expand the amino acid alphabet. In this
      tutorial review, we briefly outline different enzyme engineering strategies and
      then discuss examples where engineering has generated new 'ncAA synthases' for
      efficient, environmentally benign production of a wide and growing collection of
      valuable ncAAs.

PMID- 30280155
TI  - Reactive nano-patterns in triple structured bio-inspired honeycomb films as a
      clickable platform.
AB  - A hierarchically structured platform was obtained from directed self-assembly of
      a poly(styrene)-b-poly(4-vinylbenzylchloride) (PS-b-PVBC) block copolymer (BCP)
      during breath figure (BF) templating. The BF process using a water/ethanol
      atmosphere gave a unique double porosity in which hexagonally arranged micron
      sized pores were encircled by a secondary population of smaller, nano-sized
      pores. A third level of structuration was simultaneously introduced between the
      pores by BCP self-assembly to form out-of-the-plane nano-cylinders, offering a
      film with an unprecedented triple structure, which could be used as a reactive
      platform. Indeed the surface nano-domains of VBC were exploited as reactive nano
      patterns for site-specific chemical functionalization.

PMID- 30280156
TI  - CGG repeat DNA assisted dimerization of CGG/CGG binding molecule through
      intermolecular disulfide formation.
AB  - A new DNA binding small molecule, NCD-CC is reported. NCD-CC has a NCD domain,
      which recognizes the G-G mismatch in a CGG/CGG triad, and a cysteinylcystein (CC)
      moiety. Dimerization of NCD-CC through intermolecular disulfide bond formation
      was accelerated in the presence of CGG repeat DNA.

PMID- 30280157
TI  - Photoreduction of ferricytochrome c in the presence of potassium ferrocyanide.
AB  - Ferricytochrome c has been previously shown to photoreduce in the presence of
      ferrocyanide anions, but the process has been poorly understood. Here, we propose
      a kinetic model for this phenomenon and support it with resonance Raman
      measurements that show a clear dependence of photoreduction on the concentration
      of mixture components and laser power. Our data are consistent with the
      photoreduction process that is driven by photoexcitation of the heme followed by
      an electron transfer from the excited state of the heme macrocycle to the heme
      iron. Concomitantly, the hole in the heme ground state is filled with an electron
      transferred from a ferrocyanide ion residing in the heme pocket.

PMID- 30280158
TI  - Highly enantioselective addition of dimethylzinc to fluorinated alkyl ketones,
      and the mechanism behind it.
AB  - Chiral-diamine catalyzed addition of ZnMe2 to PhC(O)CF2X (in dichloromethane at 
      30  degrees C) affords fluorinated alkyl tertiary alcohols in high yield
      (quantitative for X = H, F, Cl; 84% for X = CF3) and up to 99% ee. These
      conditions are similarly very efficient for other various ArC(O)CF3 molecules. A
      fine analysis of the results can be performed based on a double-cycle mechanism.

PMID- 30280159
TI  - An integrated micro-millifluidic processing system.
AB  - The development of integrated microfluidic systems/platforms concerns many
      fields. Current remarkable integrated systems based on stacking multi-layer
      polydimethylsiloxane (PDMS) require complicated fabrication and operation and
      still remain challenging. We propose a novel micro-millifluidic processing system
      (MPS) comprising three core modules: a motherboard, a control panel and
      microfluidic chips. Fluids are handled in sub-millichannels in a motherboard and
      functional operations occur in microchannels in microfluidic chips. A motherboard
      with versatile functional units for fluid handling was monolithically fabricated
      via multimaterial 3D printing, which avoids multi-layer structures, and the major
      disadvantage of current 3D printing, i.e. low resolution, has been overcome by
      integrating novel microfluidic chips based on our developed maskless lithography
      platform. Both numerical and experimental studies were conducted to validate our
      system. Potential applications such as droplet generation and distribution,
      microfluidic mixing and simple bacterial resistance tests have been demonstrated
      via our MPS.

PMID- 30280160
TI  - Multi-wavelength tailoring of a ZnGa2O4 nanosheet phosphor via defect
      engineering.
AB  - The multi-wavelength luminescence tailoring of an individual phosphor free of
      external dopants is of great interest and technologically important for practical
      applications. Using ZnGa2O4 nanosheets as a target phosphor, we demonstrate how
      to artificially control the luminescence wavelength centers and their emission
      intensities to simultaneously emit ultraviolet/blue, green and red light via a
      feasible defect engineering strategy. Simple high-temperature annealing of
      hydrothermally synthesized ZnGa2O4 nanosheets leads to the effective tunability
      of their emission process to present multi-wavelength luminescence due to the
      structural distortion and the formation of oxygen vacancies. Controlling the
      annealing temperature and time can further precisely modulate the wavelengths and
      their corresponding intensities. It is speculated that the migration of Ga into
      the [GaO4] tetrahedron and the O vacancy are responsible for the multi-wavelength
      luminescence of the ZnGa2O4 nanosheet phosphor. Finally, the tentative multi
      wavelength luminescence behavior of the ZnGa2O4 nanosheet phosphor via defect
      engineering is discussed based on a series of evidenced experimental observations
      of XRD, XPS, HRTEM and CL.

PMID- 30280161
TI  - Fuel-independent and membrane-less self-charging biosupercapacitor.
AB  - We present a fuel-independent self-charging biosupercapacitor comprising an
      oxygen reducing enzymatic biocathode and an opposing bioelectrode, in which the
      supercapacitive properties of immobilised protein were utilised. Our findings
      disclose a novel hybrid type of bioelectrochemical systems, which can potentially
      be employed as an autonomous power supplier under substrate-deficient conditions.

PMID- 30280162
TI  - Encoding function into polypeptide-oligonucleotide precision biopolymers.
AB  - We report a novel synthesis strategy to prepare precision polymers providing
      exact chain lengths, molecular weights and monomer sequences that allow post
      modifications by convenient DNA hybridization. Two grafted single strand DNA
      (ssDNA) side chains serve as a versatile platform for sequence-specific
      attachment of chromophores, proteins, cell-targeting peptide, and a Y-shape DNA
      linker. This approach resembles a LEGO(r)-type incorporation of functionalities
      to create functional biopolymers of high structure definition under mild
      conditions.

PMID- 30280163
TI  - Achieving high-performance nitrate electrocatalysis with PdCu nanoparticles
      confined in nitrogen-doped carbon coralline.
AB  - Complex porous carbon nanostructures with homogeneously embedded nanoparticles
      and intricate architectures show promise as high-performance catalysts. Herein,
      we demonstrate a direct surfactant co-assembly approach for the fabrication of
      well-dispersed PdCu nanoparticles encapsulated in N-doped porous carbon with
      three-dimensional coralline structures. Owing to their porous features and unique
      frameworks, the PdxCuy@N-pC coralline-like nanostructures offer large surface
      areas, accessible active sites, and excellent nitrate electrocatalytic ability.
      The composite catalyst Pd4Cu4@N-pC exhibits outstanding catalytic performance
      with a high nitrate removal rate of ~95%, nitrogen selectivity of ~80%, and
      removal capacity of 22 000 mg N per g PdCu. More importantly, the present work
      opens up a broad horizon for architectures of nanoparticles confined in coralline
      like 3D porous carbon structures with superior performance and promising large
      scale applications.

PMID- 30280164
TI  - Modified surface states of NaGdF4:Yb3+/Tm3+ up-conversion nanoparticles via a
      post-chemical annealing process.
AB  - An amorphous layer acting as a quenching center at the surface of oleic acid
      capped NaGdF4:Yb3+/Tm3+ nanoparticles is observed directly, which can be
      reconstructed via a novel post-chemical annealing process. The amorphous phase of
      the surface layer of NaGdF4:Yb3+/Tm3+ nanoparticles gradually crystallizes as the
      post-chemical annealing temperature increases; meanwhile, the good dispersibility
      of the as-obtained nanoparticles is maintained. The reduction of surface defects
      and higher local symmetry of the crystal field environment around the doped rare
      earth ions contribute to drastically increased up-conversion (UC) emission
      intensity of the NaGdF4:Yb3+/Tm3+ nanoparticles. In particular, the blue emission
      of Tm3+ at 450 nm enhances 10-fold after the post-chemical annealing process at
      250  degrees C compared with the counterpart without further surface-state
      treatments. The color gamut of well-crystallized NaGdF4:Yb3+/Tm3+ with a modified
      surface covers the blue to yellow region in CIE chromaticity coordinates via a
      non-steady-state UC process. The results indicate that the surface states of
      these UC nanoparticles can be feasibly improved via the post-chemical annealing
      process without encouraging agglomeration, which further optimizes their UC
      properties for practical applications.

PMID- 30280165
TI  - Expedient stereospecific Co-catalyzed tandem C-N and C-O bond formation of N
      methylanilines with styrene oxides.
AB  - Cobalt(ii)-catalyzed stereospecific coupling of N-methylanilines with styrene
      oxides is developed via tandem C-N and C-O bond formation using tert-butyl
      hydroperoxide (TBHP) as an oxidant. Optically active epoxide can be reacted with
      high optical purity.

PMID- 30280166
TI  - Detection of opium alkaloids in a Cypriot base-ring juglet.
AB  - A method has been developed for extracting poppy alkaloids from oily matrices,
      specifically lipid residues associated with archaeological ceramics. The protocol
      has been applied to fresh and artificially aged poppyseed oil and to residue from
      a Late Bronze Age Cypriot juglet in the collections of the British Museum. The
      juglet is of a type that has been linked with ancient trade in opium due to its
      poppy-head shape and wide distribution; it is a rare example of an intact vessel
      with contents sealed inside. Bulk analysis of the residue by GC-EI-MS and pyGC-EI
      MS indicated a degraded plant oil and possible presence of papaverine. Analysis
      of the alkaloid extracts by HPLC-ESI-MS using both triple quadrupole and FTICR
      mass spectrometers detected the five primary opium alkaloids in fresh poppyseed
      oil and papaverine in most of the aged samples. Papaverine and thebaine were
      detected in the juglet residue, providing the first rigorous chemical evidence to
      support a link between this vessel type and opium, or at least poppies. The
      association of opium with oil raises new questions about the ancient purpose of
      the commodities within these vessels, and the low levels (ng g-1) of opiates
      detected in this unusually well-preserved residue shed doubt on the scope for
      their detection in more fragmentary ceramic remains (potsherds). Papaverine was
      found to exhibit challenging carryover behaviour in all the analytical methods
      used in this study. The phenomenon has not been reported before and should be
      considered in future analyses of this analyte in all application areas.

PMID- 30280167
TI  - The fluorescent biomarkers for lipid droplets with quinolone-coumarin unit.
AB  - Two quinolone-coumarin skeleton derivatives (1a, 1b) have been prepared by
      Friedlander synthesis with 2-aminoaryl ketone and 3-acetyl-7
      diethylaminocoumarin. The dyes showed excellent photo stability. Their optical
      properties in five organic solvents have been measured, and the wavelength range
      of the maximum fluorescence emission peaks was from 469 nm to 509 nm. Besides,
      both of them exhibited high fluorescence quantum yields (0.79-0.96) in these
      organic solvents. The pH influenced optical properties tests indicated dyes 1a-b
      have strong fluorescence in sub acid (pH = 6.0) to alkaline environment (pH =
      9.0). Their fluorescence quantum yields in neutral aqueous solution (pH = 7.0)
      were 0.82 (1a) and 0.78 (1b) respectively. In addition, dyes 1a-b exhibited
      stable fluorescence intensity in the presence of some metal cations and
      biomolecules in neutral solution (pH = 7.0). Subsequently, confocal microscopy
      imaging indicated that dyes 1a-b could be used as biomarkers for lipid droplets
      in living and fixed cells (I929 and HeLa cells).

PMID- 30280168
TI  - Understanding the axial chirality control of quinidine-derived ammonium cation
      directed O-alkylation: a computational study.
AB  - As a privileged chiral scaffold, cinchona alkaloid and its derivatives have
      reached remarkable success in catalytic asymmetric organic synthesis. In addition
      to the wide applications of point chirality control, Smith and co-workers
      recently discovered a quinidine-derived ammonium cation-catalyzed O-alkylation of
      tetralones, providing an effective approach for the synthesis of axially chiral
      biaryls. Using density functional theory (DFT) calculations, we studied the
      reaction mechanism and origins of enantioselectivity of this novel
      transformation. A stepwise strategy is adopted to ensure efficient and thorough
      exploration of the massive conformational space of transition state. Our
      computations suggested that enolate oxygen forms two hydrogen bonds with the
      chiral ammonium catalyst, and the non-covalent interactions between the cationic
      benzylic fragment and the methoxy group of enolate plays a critical role in
      determining the enantioselectivity.

PMID- 30280169
TI  - Temperature dependence of dynamic, tunnelling and kinetic isotope effects in
      formate dehydrogenase.
AB  - The origin of the catalytic power of enzymes has been a question of debate for a
      long time. In this regard, the possible contribution of protein dynamics in
      enzymatic catalysis has become one of the most controversial topics. In the
      present work, the hydride transfer step in the formate dehydrogenase (FDH EC
      1.2.1.2) enzyme is studied by means of molecular dynamic (MD) simulations with
      quantum mechanics/molecular mechanics (QM/MM) potentials in order to explore any
      correlation between dynamics, tunnelling effects and the rate constant. The
      temperature dependence of the kinetic isotope effects (KIEs), which is one of the
      few tests that can be studied by experiments and simulations to shed light on
      this debate, has been computed and the results have been compared with previous
      experimental data. The classical mechanical free energy barrier and the number of
      recrossing trajectories seem to be temperature-independent while the quantum
      vibrational corrections and the tunnelling effects are slightly temperature
      dependent over the interval of 5-45  degrees C. The computed primary KIEs are in
      very good agreement with previous experimental data, being almost temperature
      independent within the standard deviations. The modest dependence on the
      temperature is due to just the quantum vibrational correction contribution. These
      results, together with the analysis of the evolution of the collective variables
      such as the electrostatic potential or the electric field created by the protein
      on the key atoms involved in the reaction, confirm that while the protein is well
      preorganised, some changes take place along the reaction that favour the hydride
      transfer and the product release. Coordinates defining these movements are, in
      fact, part of the real reaction coordinate.

PMID- 30280170
TI  - Direct observation of Mg2+ complexes in ionic liquid solutions by 31Mg beta-NMR
      spectroscopy.
AB  - NMR spectra of Mg2+ ions in ionic liquids were recorded using a highly sensitive
      variant of NMR spectroscopy known as beta-NMR. The beta-NMR spectra of MgCl2 in
      EMIM-Ac and EMIM-DCA compare favourably with conventional NMR, and exhibit
      linewidths of ~3 ppm, allowing for discrimination of species with oxygen and
      nitrogen coordination.

PMID- 30280171
TI  - Bi2Se3 nanoplates for contrast-enhanced photoacoustic imaging at 1064 nm.
AB  - Photoacoustic (PA) imaging is a high-resolution biomedical imaging modality,
      which can be used to visualize biological tissues located beyond the limited
      penetration depth of existing optical imaging techniques. An optical wavelength
      of 1064 nm is of great interest in PA imaging due to low intrinsic absorption at
      this wavelength. Reduced absorption implies an increased depth of imaging, which
      enables several new clinical applications such as bladder imaging,
      gastrointestinal (GI) imaging, and sentinel lymph node (SLN) imaging. In
      addition, a 1064 nm Nd:YAG laser system enables a high power, cost-effective, and
      compact laser-based PA imaging system. However, at this wavelength, due to low
      intrinsic contrast, high absorption exogenous PA contrast agents are necessary
      for imaging. To this end, we present new Bi2Se3 nanoplates as PA contrast agents
      at 1064 nm wavelength for PA imaging. We successfully synthesized Bi2Se3
      nanoplates and they exhibited relatively strong PA signals at 1064 nm. We
      confirmed the increased imaging depth of penetration by imaging the Bi2Se3
      containing tube located 4.6 cm deep in biological tissues. We present in vivo PA
      imaging of the bladder, GI tract, and SLN in mice using a Bi2Se3 contrast agent
      establishing the clinical feasibility of these agents with a clinical
      photoacoustic/ultrasound imaging system. Our results confirm that Bi2Se3
      nanoplates are promising PA contrast agents at 1064 nm that offer a high optical
      absorbance in the second NIR region providing a high contrast imaging and
      increased depth of penetration.

PMID- 30280172
TI  - Effects of thermal disorder on the electronic structure of halide perovskites:
      insights from MD simulations.
AB  - The effects of thermal disorder on the electronic properties of organic/inorganic
      halide perovskites were investigated using ab initio molecular dynamics
      simulations. It was generally found that band gap variations due to effects of
      thermal disorder are the largest in materials with the smallest lattice constant.
      The factors that may lead to departure from this trend include the degree of
      rotational and translational motion of the organic cation and the strength of its
      dipole. It was found that the contribution of the flexible organic part to the
      band gap variations is considerably smaller than the contribution of the
      inorganic part of the material. The results of our simulations indicate that band
      gap variations in halide perovskites fall within the range exhibited in inorganic
      semiconductors.

PMID- 30280173
TI  - Label-free imaging of epidermal growth factor receptor-induced response in single
      living cells.
AB  - Epidermal growth factor receptor (EGFR), which belongs to the second-largest
      protein family for cell signal transduction, plays crucial roles in homeostasis,
      cellular organized patterns and most human cancers. In EGFR-activated signaling
      networks, the detection of the spatial and temporal dynamics of cascades that
      encode the many cell fates is still a challenge. Here, we report real-time
      imaging of epidermal growth factor (EGF)-induced EGFR activation and its
      signaling cascade in single A431 cells using surface plasmon resonance (SPR)
      microscopy. A two-phase SPR response pattern was observed within 30 min after EGF
      treatment, including a positive SPR response that was related to the EGFR
      activated mass redistribution in the first 600 s, and a subsequent negative SPR
      signal caused by the morphological change of the cells. Furthermore, the
      inhibitor analysis verified that AG1478 inhibited the response from the whole the
      cell, whereas cytochalasin B strongly inhibited the response from the cell edge
      region.

PMID- 30280174
TI  - Characteristics of the excited triplet states of thiolated guanosine derivatives
      and singlet oxygen generation.
AB  - Thioguanine is sensitive to UVA light and generates singlet molecular oxygen
      (1O2*) when exposed to UVA. Three thioguanosine derivatives, 2',3',5'-tri-O
      acetyl-6-thioguanosine (ta6TGuo), 2',3',5'-tri-O-acetyl-8-thioguanosine
      (ta8TGuo), and 2',3',5'-tri-O-acetyl-6,8-dithioguanosine (taDTGuo) were explored
      photophysically and photochemically. Nanosecond transient absorption and time
      resolved near-infrared emission measurements were carried out to investigate the
      characteristics of their excited triplet states in acetonitrile solution. The
      quantum yield of intersystem crossing (PhiISC), the intrinsic decay rate constant
      (k0), the quenching rate constant by 3O2 (kq) and the self-quenching rate
      constant (kSQ) of their triplet states were all determined. From the precise
      analysis of the quantum yield of 1O2* generation (PhiDelta) against the
      concentration of dissolved molecular oxygen, the fraction of the triplet states
      quenched by dissolved oxygen which gives rise to 1O2* formation (SDelta) was
      successfully obtained with high accuracy. The PhiDelta values at low oxygen
      concentrations reveal that these thioguanosines, particularly taDTGuo, can still
      effectively generate 1O2* at low molecular oxygen concentrations like
      carcinomatous microenvironments. These findings indicate that taDTGuo would
      perform well as a potential agent for photo-induced cancer therapies.

PMID- 30280175
TI  - Ferromagnetically coupled dinuclear MII complexes based on a boratriazine ligand
      framework.
AB  - A boratriazine ligand, which incorporates attractive features from both bodipy
      and terpy, has been used to synthesize [Fe2II(MU1,1-N3)2(Py2F2BTA)2(N3)2] (1) and
      [Co2II(MU1,1-N3)2(Py2F2BTA)2(N3)2] (2). Both 1 and 2 feature a double end-on
      azido bridging motif, which promotes ferromagnetic interactions between the metal
      centres. Indeed, 1 represents the first report of a dinuclear FeII complex with
      this bridging mode exhibiting J = 5.7(9) cm-1 and D = -6.0(4) cm-1, while the
      isostructural Co analogue shows J = 7.1(9) cm-1 and D = 17.3(9) cm-1.

PMID- 30280176
TI  - Controlling stacking order and charge transport in pi-stacks of aromatic
      molecules based on surface assembly.
AB  - Here, we report a facile procedure based on surface self-assembly for controlling
      the pi-pi stacking order and relevant rectified charge transport properties in
      stacks of aromatic molecules on a single-molecule scale. A high rectification
      ratio of 10 was achieved and the rectification direction was uniquely determined
      by the controlled stacking order of the aromatic molecules on the graphene layers
      of HOPG.

PMID- 30280177
TI  - A sulphur and uranium fiesta! Synthesis, structure, and characterization of
      neutral terminal uranium(vi) monosulphide, uranium(vi) eta2-disulphide, and
      uranium(iv) phosphine sulphide complexes.
AB  - Three new uranium species (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2
      C6H3)([double bond, length as m-dash]S), (C5Me5)2U([double bond, length as m
      dash]N-2,6-iPr2-C6H3)(eta2-S2), and (C5Me5)2U([double bond, length as m-dash]N
      2,6-iPr2-C6H3)(S[double bond, length as m-dash]PMe3) were synthesized and fully
      characterized by a combination of NMR, IR, and UV/vis-NIR spectroscopies,
      elemental analysis, and cyclic voltammetry. The solid state structures of
      (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)([double bond, length as
      m-dash]S) and (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)(eta2-S2)
      were also determined. The compound (C5Me5)2U([double bond, length as m-dash]N-2,6
      iPr2-C6H3)([double bond, length as m-dash]S) is the first neutral uranium complex
      with a terminal sulphido ligand, and (C5Me5)2U([double bond, length as m-dash]N
      2,6-iPr2-C6H3)(S[double bond, length as m-dash]PMe3) is the first uranium
      compound with a coordinated phosphine sulphide ligand. The phosphine sulphide
      adduct, (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)(S[double bond,
      length as m-dash]PMe3), can be synthesized either by reaction of the uranium(iv)
      complex (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)(thf) with
      S[double bond, length as m-dash]PMe3 or by the reaction of the uranium(vi)
      terminal sulphido complex (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2
      C6H3)([double bond, length as m-dash]S) with PMe3.

PMID- 30280178
TI  - Palladium-catalyzed heck-type cascade cyclization of (Z)-1-iodo-1,6-dienes with N
      tosyl hydrazones.
AB  - A palladium-catalyzed heck-type cascade cyclization of (Z)-1-iodo-1,6-dienes with
      N-tosyl hydrazones is reported. The alkylpalladium intermediate coupled with the
      diazo compound, generating the second alkylpalladium species bearing two beta-H,
      which generated a terminal alkene as the major products in the anti-Zaitsev way
      via the highly regioselective beta-H elimination. It provided a new way to
      synthesize tetrahydropyridine derivatives bearing a terminal alkene.

PMID- 30280179
TI  - Single-compartment hydrogen peroxide fuel cells with poly(3,4
      ethylenedioxythiophene) cathodes.
AB  - Single-compartment hydrogen peroxide fuel cells have recently emerged as a
      promising energy conversion platform since H2O2 is a high energy-density liquid
      that functions as both fuel and oxidizer. Finding suitable electrocatalysts is
      challenging since most metallic electrodes also catalyze the disproportionation
      reaction of H2O2 into H2O and O2, representing a significant loss mechanism in
      peroxide fuel cells. Herein we demonstrate that the conducting polymer poly(3,4
      ethylenedioxythiophene), PEDOT, is a versatile electrocatalyst for peroxide fuel
      cells without generating losses due to disproportionation. We find that PEDOT is
      a cathodic catalyst for reduction of peroxide to water, performing at a level on
      par with the best reported inorganic catalysts. Using PEDOT as the cathode and
      nickel as the anode material, open circuit potentials in the range of 0.5-0.6 V
      are possible, with power densities of 0.20-0.30 mW cm-2. We provide evidence to
      understand mechanistically how PEDOT functions as a catalyst for hydrogen
      peroxide reduction to water. The result of our efforts is a scalable hydrogen
      peroxide fuel cell cathode, which serves to demonstrate also the capabilities of
      organic semiconducting materials as electrocatalysts.

PMID- 30280180
TI  - Arsenene nanoribbon edge-resolved strong magnetism.
AB  - We proposed a mechanism to induce strong magnetism of up to 10.92 emu g-1 in
      hexagonal-phase arsenene nanoribbon (AsNR) from the perspective of edge quantum
      entrapment. Consistency between bond-order-length-strength correlation (BOLS)
      theory and density functional theory (DFT) calculations verified that: (i) the
      edge bond contraction of 9.54% deepened the edge potential well of AsNR, (ii) a
      net charge of 0.06 e- transferred from the inner region to the edge; and (iii)
      the edge quantum well polarized the unpaired electron and the net spin
      (antiferromagnetic or ferromagnetic depending on the width) is localized at the
      zigzag edge. The finding sheds a light on applications of AsNR in magnetic
      storage devices.

PMID- 30280181
TI  - Movement of palladium nanoparticles in hollow graphitised nanofibres: the role of
      migration and coalescence in nanocatalyst sintering during the Suzuki-Miyaura
      reaction.
AB  - The evolution of individual palladium nanoparticle (PdNP) catalysts in
      graphitised nanofibres (GNF) in the liquid-phase Suzuki-Miyaura (SM) reaction has
      been appraised. The combination of identical location-transmission electron
      microscopy (IL-TEM) and a nano test tube approach allowed spatiotemporally
      continuous observations at the single nanoparticle level, revealing that
      migration and coalescence is the most significant pathway to coarsening of the
      nanocatalyst, rather than Ostwald ripening. IL-TEM gave unprecedented levels of
      detail regarding the movement of PdNP on carbon surfaces at the nanoscale,
      including size-dependent migration and directional movement, opening horizons for
      the optimisation of future catalysts through surface morphology design.

PMID- 30280182
TI  - The role of focal adhesion kinase in transforming growth factor-beta2 induced
      migration of human lens epithelial cells.
AB  - The migration of lens epithelial cells towards the posterior capsule is a key
      event in the development of posterior capsule opacification (PCO). Accumulating
      evidence has described crosstalk between growth factors and adhesive signaling
      pathways in wound healing and cell migration. The aim of the present study was to
      elucidate an aberrant transforming growth factor (TGF)-beta2 signaling pathway
      that regulated the migration of lens epithelial cells in the pathological context
      of PCO. The expression of fibronectin, focal adhesion kinase (FAK) and
      phosphorylated (p)-FAK in HLE-B3 cells following TGF-beta2 treatment was
      determined by western blot analysis and the expression of integrin alpha5beta1
      was detected by flow cytometry. Cell migration capacity was measured by wound
      healing and Transwell assays in the presence of 1,2,4,5-tetraaminobenzene
      tetrahydrochloride, a selective FAK inhibitor, fibronectin small interfering RNA
      interference, arginylglycylaspartic acid peptides or alpha5beta1-integrin
      neutralizing antibodies. The 1,2,4,5-tetraaminobenzene tetrahydrochloride was
      administered daily to 16 rabbits following cataract surgery. Fibronectin and TGF
      beta expression were increased in the PCO group, demonstrated by
      immunofluorescence assays. PCO grading was conducted by slit-lamp biomicroscopy
      and evaluation of posterior capsule opacification software. It was observed that
      TGF-beta2 promoted HLE-B3 cell migration and upregulated fibronectin expression,
      which was followed by an increased phosphorylation of FAK. In addition, TGF-beta2
      treatment and fibronectin surface coating significantly increased cell migration
      and FAK activation, which was inhibited by disrupting fibronectin-integrin
      alpha5beta1 interaction with the arginylglycylaspartic acid peptide, alpha5beta1
      integrin neutralizing antibody or fibronectin depletion. Finally, suppression of
      FAK signaling by its inhibitor significantly decreased cell migration in vitro
      and attenuated PCO development in vivo. In summary, TGF-beta2 was indicated to
      promote the migration of lens epithelial cells through the TGF
      beta2/fibronectin/integrin/FAK axis. Inhibition of FAK activity decreased TGF
      beta2-mediated cell migration in vitro and improved the symptoms of PCO in a
      rabbit model.

PMID- 30280183
TI  - Protective effect of luteolin on skin ischemia-reperfusion injury through an AKT
      dependent mechanism.
AB  - Cutaneous ischemia-reperfusion (I/R) injury is one of the most crucial problems
      in flap surgery, which affects the survival of the skin flap and patient
      prognosis, luteolin, a plant derived flavonoid, has previously been shown to
      exert a variety of beneficial effects for reducing I/R injury in several organs.
      The aim of the present study was to evaluate the anti-inflammatory and anti
      oxidative stress effects of luteolin on cutaneous I/R injury. The in vitro study
      were performed using a permanent human immortalized epidermal keratinocyte cell
      line (HaCaT), cells were cultured in the presence of luteolin and were then
      treated with hydrogen peroxide, the cell viability, mitochondrial membrane
      potential and the cell survival/apoptosis related signaling pathway activation
      were assessed to investigate the cytoprotective effects of luteolin. For in vivo
      experiments, skin flap I/R injury animal model was established in Sprague-Dawley
      rats, by measuring the area of flap survival, analyzing the expression of pro
      inflammatory cytokine and evaluation of the histological changes in the skin
      tissue, the protective effects of luteolin on skin I/R injury were investigated.
      The function of protein kinase B (AKT) and heme oxygenase-1 (HO-1) activation on
      luteolin mediated I/R injury protection was assessed by administration of
      phosphoinositide-3-kinase/AKT inhibitor LY294002 and HO-1 inhibitor ZNPP. The
      results showed that luteolin treatment significantly increased the viability of
      HaCaT cells upon exposure to hydrogen peroxide, and the administration of
      luteolin in vivo significantly improved skin flap survival in the I/R injury rat
      model. The mechanisms underlying these beneficial effects included increased
      phosphoinositide-3-kinase/protein kinase B activation, improved expression of
      antioxidant enzyme, and scavenging the cytotoxic effects of reactive oxygen
      species (ROS). Taken together, the results suggested that luteolin
      preconditioning yielded significant protection against cutaneous I/R injury by
      protecting skin keratinocytes from ROS-induced damage.

PMID- 30280185
TI  - Suppressing cell growth and inducing apoptosis by inhibiting miR-23a-5p in human
      bladder cancer.
AB  - MicroRNAs (miRNAs) are a class of non-coding RNAs, which are important in the
      initiation and progression of cancer. miRNA-23a-5p (miR-23a-5p) is a novel miRNA,
      which promotes cell growth and survival in several types of cancer. The aim of
      the present study was to investigate the expression and functional significance
      of miR-23a-5p in bladder cancer. Microchip assays have shown that miR-23a-5p is
      significantly upregulated in human bladder cancer. In the present study, it was
      found that miR-23a-5p was upregulated in bladder cancer tissues, compared with
      paired normal urothelial tissues by reverse transcription-quantitative polymerase
      chain reaction. The impact of miR-23a-5p on cell proliferation, cell migration
      and apoptosis was determined by a 3-(4,5-dimethylthi-azol-2-yl)-2,5
      diphenyltetrazolium bromide assay, wound scratch assay and flow cytometry. The
      inhibition of cell proliferation and induction of apoptosis were also observed in
      miR-23a-5p inhibitor-transfected T24 and SW780 human bladder cancer cells. These
      data suggested that miR-23a-5p has an oncogenic role and may be a therapeutic
      target for bladder cancer.

PMID- 30280187
TI  - Mangiferin: An effective therapeutic agent against several disorders (Review).
AB  - Mangiferin (1,3,6,7-tetrahydroxyxanthone-C2-beta-D-glucoside) is a bioactive
      ingredient predominantly isolated from the mango tree, with potent antioxidant
      activity and multifactorial pharmacological effects, including antidiabetic,
      antitumor, lipometabolism regulating, cardioprotective, anti-hyperuricemic,
      neuroprotective, antioxidant, anti-inflammatory, antipyretic, analgesic,
      antibacterial, antiviral and immunomodulatory effects. Therefore, it possesses
      several health-endorsing properties and is a promising candidate for further
      research and development. However, low solubility, mucosal permeability and
      bioavailability restrict the development of mangiferin as a clinical therapeutic,
      and chemical and physical modification is required to expand its application.
      This review comprehensively analyzed and collectively summarized the primary
      pharmacological actions of mangiferin that have been demonstrated in the
      literature, to support the potential future development of mangiferin as a novel
      therapeutic drug.

PMID- 30280184
TI  - Maintenance of intracellular Ca2+ basal concentration in airway smooth muscle
      (Review).
AB  - In airway smooth muscle, the intracellular basal Ca2+ concentration [b(Ca2+)i]
      must be tightly regulated by several mechanisms in order to maintain a proper
      airway patency. The b[Ca2+]i is efficiently regulated by sarcoplasmic reticulum
      Ca2+-ATPase 2b, plasma membrane Ca2+-ATPase 1 or 4 and by the Na+/Ca2+ exchanger.
      Membranal Ca2+ channels, including the L-type voltage dependent Ca2+ channel (L
      VDCC), T-type voltage dependent Ca2+ channel (T-VDCC) and transient receptor
      potential canonical 3 (TRPC3), appear to be constitutively active under basal
      conditions via the action of different signaling pathways, and are responsible
      for Ca2+ influx to maintain b[Ca2+]i. The two types of voltage-dependent Ca2+
      channels (L- and T-type) are modulated by phosphorylation processes mediated by
      mitogen-activated protein kinase kinase (MEK) and extracellular-signal-regulated
      kinase 1 and 2 (ERK1/2). The MEK/ERK signaling pathway can be activated by G
      protein-coupled receptors through the alphaq subunit when the endogenous ligand
      (i.e., acetylcholine, histamine, leukotrienes, etc.) is present under basal
      conditions. It may also be stimulated when receptor tyrosine kinases are occupied
      by the appropriate ligand (cytokines, growth factors, etc.). ERK1/2
      phosphorylates L-VDCC on Ser496 of the beta2 subunit and Ser1928 of the alpha1
      subunit, decreasing or increasing the channel activity, respectively, and
      enabling it to switch between an open and closed state. T-VDCC is also probably
      phosphorylated by ERK1/2, although further research is required to identify the
      phosphorylation sites. TRPC3 is directly activated by diacylglycerol produced by
      phospholipase C (PLCbeta or gamma). Constitutive inositol 1,4,5-trisphosphate
      production induces the release of Ca2+ from the sarcoplasmic reticulum through
      inositol triphosphate receptor 1. This ion induces Ca2+-induced Ca2+ release
      through the ryanodine receptor 2 (designated as Ca2+ 'sparks'). Therefore,
      several Ca2+ handling mechanisms are finely tuned to regulate basal intracellular
      Ca2+ concentrations. It is conceivable that alterations in any of these processes
      may render airway smooth muscle susceptible to develop hyperresponsiveness that
      is observed in ailments such as asthma.

PMID- 30280186
TI  - Long non-coding RNA C5orf66-AS1 prevents oral squamous cell carcinoma through
      inhibiting cell growth and metastasis.
AB  - Oral squamous cell carcinoma (OSCC) is a major cancer type in the head and neck
      region. Recent studies have reported a marked rise in the incidence of OSCC. The
      present study was performed to better understand the roles that long non-coding
      RNAs (lncRNAs) serve in OSCC carcinogenesis. The levels of the lncRNA C5orf66
      antisense RNA 1 (C5orf66-AS1) and of cytochrome c1 (CYC1) in OSCC tissues and
      cells were measured through reverse transcription-quantitative polymerase chain
      reaction. In addition, the levels of associated proteins were analyzed by western
      blotting, while MTT assay was used to detect the cell proliferation ability.
      Wound healing and transwell assays were also used to detect the migration and
      invasion abilities of OSCC cells in the experimental groups, while flow cytometry
      was applied to analyze cell apoptosis. The findings revealed that the expression
      of lncRNA C5orf66-AS1 in OSCC tissues and cells was significantly decreased.
      Overexpression of lncRNA C5orf66-AS1 significantly inhibited the proliferation,
      invasion and migration ability of OSCC cells, and promoted cell apoptosis, while
      lncRNA C5orf66-AS1 downregulation presented the opposite effects. In addition, it
      was observed that CYC1 was upregulated in OSCC tissues and cells, and was
      negatively regulated by lncRNA C5orf66-AS1. Notably, CYC1 silencing markedly
      eliminated the effects of lncRNA C5orf66-AS1 downregulation on OSCC cells. Taken
      together, these findings indicated that lncRNA C5orf66-AS1 may prevent OSCC
      progression by inhibiting OSCC cell growth and metastasis via the regulation of
      CYC1 expression.

PMID- 30280188
TI  - Ketamine destabilizes growth of dendritic spines in developing hippocampal
      neurons in vitro via a Rho-dependent mechanism.
AB  - The safety of anesthetics on the developing brain has caused concern. Ketamine,
      an N-methyl-D-aspartate receptor antagonist, is widely used as a general
      pediatric anesthetic. Recent studies suggested that ketamine alters the
      plasticity of dendritic spines in the developing brain and may be an important
      contributing factor to learning and cognitive impairment. However, the underlying
      molecular mechanism remains poorly understood. Therefore, the aim of the present
      study was to investigate the effect of ketamine on the plasticity of dendritic
      spines in cultured hippocampal neurons and the potential underlying mechanisms.
      After 5 days in vitro, rat hippocampal neurons were exposed to different
      concentrations (100, 300 and 500 uM) of ketamine for 6 h. Ketamine decreased the
      number and length of dendritic spines in a dose-dependent manner. Ketamine at a
      concentration of 300 uM caused an upregulation of transforming protein RhoA
      (RhoA) and Rho-associated kinase (ROCK) protein. These effects were inhibited by
      the ROCK inhibitor Y27632. These results suggested that ketamine induces loss and
      shortening of dendritic spines in hippocampal neurons via activation of the
      RhoA/ROCK signaling pathway.

PMID- 30280189
TI  - MrgX2-mediated internalization of LL-37 and degranulation of human LAD2 mast
      cells.
AB  - LL-37 is the sole antimicrobial peptide of human cathelicidin comprising 37 amino
      acids, which is expressed mainly in epithelial cells and neutrophils, and
      activates mast cells. In the present study, in order to elucidate the mechanism
      of mast cell activation by LL-37, the associations between the internalization of
      LL-37 and Mas-related gene X2 (MrgX2)-mediated mast cell activation
      (degranulation) was investigated using the human mast cell line, LAD2. LL-37 was
      rapidly internalized into the cells, and induced degranulation, as assessed by
      the extracellular release of beta-hexosaminidase. Pertussis toxin, a G-protein
      inhibitor, significantly suppressed the internalization of LL-37 and the
      degranulation of LAD2 cells. Furthermore, small interfering (si)-RNA-mediated
      knockdown of MrgX2, a putative G protein-coupled receptor for LL-37, inhibited
      the internalization of LL-37 and degranulation of LAD2 cells. Notably, LL-37
      internalization was enhanced by the stable expression of MrgX2 in HMC-1 and 293
      cells. In addition, the internalized LL-37 mainly colocalized with MrgX2 in the
      perinuclear region of LAD2 cells. Furthermore, neuraminidase treatment, which
      removes negatively charged sialic acid from the cell surface, markedly reduced
      the internalization of LL-37 and degranulation of LAD2 cells, and clathrin
      mediated endocytosis inhibitors (dynasore and chlorpromazine) inhibited the
      internalization and degranulation of LAD2 cells. Taken together, these
      observations indicated that LL-37 may bind the negatively charged cell surface
      molecules, rapidly internalize into the cells via clathrin-mediated endocytosis
      and interact with MrgX2 to activate mast cells (LAD2 cells).

PMID- 30280190
TI  - Secretogranin III may be an indicator of paraquat-induced astrocyte activation
      and affects the recruitment of BDNF during this process.
AB  - Astrocyte activation has been described as a multi-stage defensive response,
      which is characterized by the morphological alteration of astrocytes and the
      overexpression of intermediate filament proteins. However, the functional
      mechanism of the secretion system in activated astroglia remains unclear. It has
      previously been demonstrated that secretogranin II, a member of the granin
      family, may be involved in the sorting and expression of inflammatory factors and
      excitatory neurotransmitters in paraquat (PQ)-induced astroglial activation.
      Secretogranin III (SCG3) has been reported to represent an important component of
      the regulated secretory pathway in neuroendocrine cells; however, its role as an
      anchor protein of dense-core vesicles in astrocytes remains to be elucidated. In
      the present study, a PQ-activated U118MG astrocytoma cell model established in
      our previous study was used to investigate the effects of SCG3. The results
      revealed that SCG3 was highly expressed and subsequently released from cells in
      response to PQ. Inhibition of SCG3 expression via transfection with small
      interfering RNA partially restored astrocyte morphology, but did not affect the
      expression of astrocytic factors. Further studies investigating the association
      between SCG3 and other cellular factors were conducted, in order to determine the
      expression levels and subcellular localization of these proteins. Neurotrophins
      and inflammatory factors exhibited an increase in characteristic expression
      patterns, paralleling the alterations in SCG3 expression. The results further
      demonstrated that brain-derived neurotrophic factor partially colocalized with
      SCG3-positive vesicles; however, the localization of interleukin-6 was not
      affected. In conclusion, SCG3 may be involved in PQ-induced astrocyte activation
      via regulation of the expression and selective recruitment of cellular factors,
      thus suggesting that SCG3 may represent an indicator of astrocyte activation.

PMID- 30280191
TI  - Overexpression of small ubiquitin-like modifier 2 ameliorates high glucose
      induced reductions in cardiomyocyte proliferation via the transforming growth
      factor-beta/Smad pathway.
AB  - Hyperglycemia may induce diabetic cardiomyopathy (DC). In the current study, the
      mechanism underlying the alleviation of high glucose (HG)-induced impairments in
      the proliferation of H9c2 embryo cardiomyocyte proliferation by small ubiquitin
      like modifier 2 (SUMO2) overexpression was investigated. H9c2 cell morphology was
      identified as classical long shuttle type by optical microscopy. The viability of
      HG-injured H9c2 cells was evaluated by a Cell Counting Kit-8 assay and the
      results indicated that viability was inhibited in a dose-dependent (5.6, 10, 20
      and 30 mmol/l) and time-dependent (6, 12 and 24 h) manner. H9c2 cells treated
      with 20 mmol/l HG for 24 h were selected for subsequent experiments due to the
      extent of injury caused at a low density. Flow cytometry was conducted to confirm
      cell cycle arrest between G1/S phases and apoptosis promotion in HG-injured H9c2
      cells, and the subsequent alleviating effect of SUMO2 overexpression on these HG
      induced effects. Reverse transcription-quantitative polymerase chain reaction (RT
      qPCR) and western blot analysis were performed to detect mRNA and protein
      expression levels of cell cycle-and apoptosis-associated factors. The results
      indicated that the expression ofthe cell cycle-associated factors CyclinA2 and C
      Myc was upregulated, and cyclin-dependent kinase inhibitor 1a was downregulated.
      The expression of the apoptosis-associated factor Bcl-2 was upregulated, while
      Bcl-2-associated X and caspase-3 expression was downregulated, by SUMO2
      overexpression. Furthermore, the effect of SUMO2 overexpression on the
      transforming growth factor (TGF)-beta/Smad pathway was also determined using RT
      qPCR and western blot analysis. The results indicated the mRNA and protein levels
      of TGF-beta1 and Smad3 in HG-injured H9c2 cells were significantly decreased
      following SUMO2 overexpression. Thus, the results demonstrated that
      overexpression of SUMO2 may alleviate H9c2 cardiomyocyte cell cycle arrest and
      apoptosis promotion induced by HG via regulation of cell cycle- and apoptosis
      associated factors, as well as inhibition of the TGF-beta/Smad pathway. These
      results may therefore provide a novel strategy for the protection of
      cardiomyocytes and may aid the diagnosis and prognosis of patients with DC.

PMID- 30280192
TI  - Whole exome sequencing identification of a novel insertion mutation in the
      phospholipase C epsilon-1 gene in a family with steroid resistant inherited
      nephrotic syndrome.
AB  - Nephrotic syndrome (NS) represents a heterogeneous group of kidney disorders
      characterized by excessive proteinuria, hypoalbuminemia and edema. Defects in the
      filtration barrier of the glomeruli results in the development of NS. The genetic
      cause of NS remains to be fully elucidated. However, previous studies based on
      positional cloning of genes mutated in NS have provided limited insight into the
      pathogenesis of this disease. Mutations in phospholipase C epsilon-1 (PLCE1) have
      been reported as a cause of early onset NS characterized by histology of diffuse
      mesangial sclerosis. In the present study, the underlying cause of NS in a
      consanguineous family was identified. Clinical and molecular aspects of a
      consanguineous Saudi family comprised of five individuals with steroid resistant
      NS were examined. Seven healthy individuals from the same family were also
      studied. Whole exome sequencing (WES) was performed to detect the genetic defect
      underlying NS. WES identified a homozygous novel insertion mutation
      (c.6272_6273insT) in the PLCE1 gene. Pedigree and segregation analysis confirmed
      an autosomal recessive inheritance pattern. This mutation may result in a bi
      allelic loss of the C-terminal Ras-associating domain in PLCE1 that results in
      NS. The present study expanded the mutational spectrum of PLCE1 in NS. In
      addition, the present study provided further evidence that supports the important
      involvement of PLCE1 in the physiological function of the glomerular filtration
      barrier.

PMID- 30280193
TI  - Evidence and perspective for the role of the NLRP3 inflammasome signaling pathway
      in ischemic stroke and its therapeutic potential (Review).
AB  - Ischemic stroke is one of the main causes of death and disablement globally. The
      NLR family pyrin domain containing 3 (NLRP3) inflammasome is established as a
      sensor of detecting cellular damage and modulating inflammatory responses to
      injury during the progress of ischemic stroke. Inhibiting or blocking the NLRP3
      inflammasome at different stages, including expression, assembly, and secretion,
      may have great promise to improve the neurological deficits during ischemic
      stroke. The current review provides a comprehensive summary of the current
      understanding in the literature of the molecular structure, expression, and
      assembly of the NLRP3 inflammasome, and highlights its potential as a novel
      therapeutic target for ischemic stroke.

PMID- 30280194
TI  - Compound pathogenic mutation in the USH2A gene in Chinese RP families detected by
      whole-exome sequencing.
AB  - Retinitis pigmentosa (RP) is a common form of inherited retinal degeneration that
      causes progressive loss of vision or adult blindness, characterized by the
      impairment of rod and cone photoreceptors. At present, mutations in >60
      pathogenic genes have been confirmed to cause RP. The predominant modes of
      inheritance are autosomal dominant, autosomal recessive and X-linked. In
      addition, other modes of inheritance, including digenic or mitochondrial
      inheritance, have been reported. In previous decades, with the development of
      sequencing techniques, significant advances in identifying novel RP pathogenic
      genes and screening mutations have been made. In the present study, whole-exome
      sequencing was performed on samples from two Chinese pedigrees diagnosed with RP.
      A compound heterozygous mutation in the gene usherin 2A (USH2A;
      c.6,485+5G>A/c.11,156G>A) and a heterozygous X-linked mutation in the gene
      retinitis pigmentosa 2 (RP2) ARL3 GTPase-activating protein (RP2; c.358C>T) were
      identified by Sanger sequencing and co-segregation analysis, of which the
      pathogenic mutation (c.6,485+5G>A) in USH2A has not been previously reported
      among Chinese patients. The findings of the present study may expand on current
      knowledge of RP among the Chinese population, providing essential assistance in
      the molecular diagnosis and screening of RP, and promoting further investigation
      of the pathogenesis of RP.

PMID- 30280196
TI  - MicroRNA-944 targets vascular endothelial growth factor to inhibit cell
      proliferation and invasion in osteosarcoma.
AB  - Emerging evidence has demonstrated that the dysregulation of microRNA (miRNA/miR)
      serves a crucial role in the tumorigenesis and tumor development of osteosarcoma
      (OS), primarily by affecting various pathological behaviors. Therefore, better
      knowledge of miRNA in OS may provide novel insights into the pathogenesis of OS,
      and may facilitate the development of promising therapeutics for patients with
      this disease. MiRNA-944 is frequently dysregulated in human cancers. However, the
      expression levels, functions and underlying mechanisms of miR-944 in OS remain
      largely elusive. In the present study, reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR) was performed to detect miR-944 expression in
      OS tissues and cell lines. The regulatory influence of miR-944 in OS
      proliferation and invasion was determined with MTT and Transwell invasion assays.
      In addition, the mechanisms underlying the action of miR-944 in OS cells were
      elucidated through a series of experiments, including bioinformatics analysis,
      luciferase reporter assay, RT-qPCR and western blot analysis. Spearman's
      correlation analysis was utilized to examine the relationship between miR-944 and
      VEGF expression levels, and rescue experiments were applied to further verify
      whether VEGF mediates the role of miR-944 in OS. The results demonstrated that
      miR-944 was downregulated in cancer tissues and cell lines. Furthermore,
      exogenous miR-944 expression inhibited cell proliferation and invasion in OS in
      vitro. Vascular endothelial growth factor (VEGF) was identified as a direct
      target of miR-944 in OS and was overexpressed in cancer tissues. VEGF expression
      was inversely correlated with miR-944 expression in cancer tissues. Rescue
      experiments demonstrated that overexpression of VEGF partially prevented the miR
      944-induced inhibition of OS cell proliferation and invasion. These results
      suggested that miR-944 may serve a tumor suppressive role in OS by directly
      targeting VEGF. Therefore, miR-944 may be a promising target in the treatment of
      OS.

PMID- 30280195
TI  - Salmonella-induced miR-155 enhances necroptotic death in macrophage cells via
      targeting RIP1/3.
AB  - Salmonella enterica serovar Typhimurium (hereafter referred to as Salmonella), a
      virulent pathogen, is known to induce host-cell death. Using reverse
      transcription-quantitative polymerase chain reaction, a 28-fold increase of
      microRNA (miR)-155 expression in RAW 264.7 macrophages was observed following
      infection with Salmonella for 24 h. This miR-155 upregulation increased
      macrophage cell death by up to 40% in 48 h following infection. Western blot
      analysis revealed that receptor interacting protein 1 (RIP1) and 3 (RIP3) were
      increased at 18 h following miR-155 transfection to macrophages, similar to
      Salmonella infection. In addition, inhibition of RIP1 by pre-incubating
      macrophages with necrostatin-1, a RIP1 specific inhibitor, increased the
      viability of Salmonella-infected cells and miR-155-transfected cells by up to
      20%. The cleavage of poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1)
      was also enhanced by miR-155 induction upon Salmonella infection. Therefore, it
      was suggested that RIP1/3-induced necroptosis and PARP-1-mediated necrosis caused
      by miR-155 induction may represent distinct routes of programmed necrotic cell
      death of Salmonella-infected macrophages.

PMID- 30280197
TI  - An RGD small-molecule integrin antagonist induces detachment-mediated anoikis in
      glioma cancer stem cells.
AB  - The malignancy of glioblastoma (GB) is primarily due to the ability of glioma
      cancer stem cells (GSC) to disseminate into surrounding brain tissues, despite
      surgery and chemotherapy, and to form new tumoral masses. Members of the RGD
      binding integrin family, which recognize the arginine-glycine-aspartic acid (RGD)
      sequence present in components of the extracellular matrix, and which serve a
      crucial function in the dissemination of GCS, are overexpressed in GB. Small
      molecule integrin antagonists (SMIAs) designed to recognize RGD-integrins may
      therefore be an effective tool for decreasing GB infiltration and recurrence. In
      the present study, in vitro pro-apoptotic and infiltrative effects elicited by
      the SMIA 1a-RGD in human GSC were investigated. Reverse transcription
      quantitative polymerase chain reaction analysis revealed that, compared with
      normal human astrocytes, GSC grown on laminin-coated dishes overexpressed
      stemness markers as well as alphavbeta3 and alphavbeta5 integrins. In addition,
      dissociated GSC were identified to exhibit tumorigenic capacity when injected
      into immunodeficient mice. Using annexin/fluorescence-activated cell sorting
      analysis and ELISA nucleosome assays, it was identified that treatment of GSC
      with 25 uM 1a-RGD for 48 h elicited detachment-dependent anoikis not accompanied
      by necrosis-dependent cell death. A colorimetric proliferation assay indicated
      that 1a-RGD did not affect cell viability, but that, instead, it markedly
      inhibited GSC migration as assessed using a Transwell assay. Western blot
      experiments revealed a decrease in focal adhesion kinase and protein kinase B
      phosphorylation with a concomitant increase in caspase-9 and -3/7 activity
      following 1a-RGD treatment, suggesting that the pro-anoikis effects of 1a-RGD may
      be mediated by these molecular mechanisms. Western blot analysis revealed no
      changes in specific markers of autophagy, suggesting further that 1a-RGD-induced
      cell death is primarily sustained by anoikis-associated mechanisms. In
      conclusion, the results of the present study indicate that SMIA have potential as
      a therapeutic tool for decreasing GSC dissemination.

PMID- 30280198
TI  - Profiling cytochrome P450 family 4 gene expression in human hepatocellular
      carcinoma.
AB  - Cytochrome P450 family 4 (CYP4) enzymes are known as microsomal omega (omega)
      hydroxylases that metabolize fatty acids, eicosanoids, vitamin D and carcinogens.
      Thus, CYP4 enzymes may influence tumor development and progression. The aim of
      the present study was to evaluate the CYP4 expression profile in hepatocellular
      carcinoma (HCC) and its clinical relevance. The present study obtained CYP4 mRNA
      expression data for 377 HCC cases from The Cancer Genome Atlas cohort and
      performed Kaplan-Meier survival, Gene Ontology functional enrichment, and gene
      set enrichment analysis (GSEA). In addition, the level of CYP4F2 protein
      expression was evaluated in matched pairs of HCC and non-tumor tissue samples and
      the results were correlated with the clinicopathological characteristics of HCC
      (n=113). HCC survival analyses indicated better overall survival in patients with
      high CYP4F2, CYP4F12 and CYP4V2 mRNA expression levels; the results for
      histological grade and Tumor-Node-Metastasis stage supported these results. GSEA
      revealed high levels of CYP4F2, CYP4F12 and CYP4V2 mRNA expression to be
      negatively correlated with the expression of cell cycle-associated genes. CYP4F2
      protein expression was higher in non-neoplastic liver tissue than in HCC tissue
      and positively correlated with favorable pathological tumor stage (I vs. II-IV;
      P=0.022) and was a good independent prognostic factor for overall survival
      (P=0.004). These results demonstrate that the expression levels of the genes
      CYP4F2, CYP4F12 and CYPV2 are favorable prognostic factors in HCC and suggest the
      potential predictive diagnostic and prognostic roles of CYP4F2, CYP4F12 and CYPV2
      gene expression in HCC.

PMID- 30280199
TI  - BML-111 suppresses TGF-beta1-induced lung fibroblast activation in vitro and
      decreases experimental pulmonary fibrosis in vivo.
AB  - Pulmonary fibrosis is an aggressive end-stage disease. Transforming growth factor
      beta1 (TGF-beta1) mediates lung fibroblast activation and is essential for the
      progress of pulmonary fibrosis. BML-111, a lipoxinA4 (LXA4) receptor (ALX)
      agonist, has been reported to possess anti-fibrotic properties. The present study
      aimed to elucidate whether BML-111 inhibits TGF-beta1-induced mouse embryo lung
      fibroblast (NIH3T3 cell line) activation in vitro and bleomycin (BLM)-induced
      pulmonary fibrosis in vivo. In vitro experiments demonstrated that BML-111
      treatment inhibits TGF-beta1-induced NIH3T3 cell viability and the expression of
      smooth muscle alpha actin (alpha-SMA), fibronectin and total collagen.
      Furthermore, this suppressive effect was associated with mothers against
      decapentaplegic homolog (Smad)2/3, extracellular signal-regulated kinase (ERK)
      and Akt phosphorylation interference. In vivo experiments revealed that BML-111
      treatment markedly improved survival rate and ameliorated the destruction of lung
      tissue structure. It also reduced interleukin-1beta (IL-1beta), tumor necrosis
      factor-alpha (TNF-alpha) and TGF-beta1 expression in the BLM intratracheal mouse
      model. In addition, the expression ofalpha-SMA and extracellular matrix (ECM)
      deposition (total collagen, hydroxyproline and fibronectin) were also suppressed
      following BML-111 treatment. However, BOC-2, an antagonist of ALX, partially
      weakened the effects of BML-111. In conclusion, these results indicated that BML
      111 inhibits TGF-beta1-induced fibroblasts activation and alleviates BLM-induced
      pulmonary fibrosis. Therefore, BML-111 may be used as a potential therapeutic
      agent for pulmonary fibrosis treatment.

PMID- 30280201
TI  - Metastatic cancer cells compensate for low energy supplies in hostile
      microenvironments with bioenergetic adaptation and metabolic reprogramming.
AB  - Metastasis accounts for the majority of cancer-related mortalities, and the
      complex processes of metastasis remain the least understood aspect of cancer
      biology. Metabolic reprogramming is associated with cancer cell survival and
      metastasis in a hostile envi-ronment with a limited nutrient supply, such as
      solid tumors. Little is known regarding the differences of bioenergetic
      adaptation between primary tumor cells and metastatic tumor cells in unfavorable
      microenvironments; to clarify these differences, the present study aimed to
      compare metabolic reprogramming of primary tumor cells and metastatic tumor
      cells. SW620 metastatic tumor cells exhibited stronger bioenergetic adaptation in
      unfavorable conditions compared with SW480 primary tumor-derived cells, as
      determined by the sustained elevation of glycolysis and regulation of the cell
      cycle. This remarkable glycolytic ability of SW620 cells was associated with high
      expression levels of hexokinase (HK)1, HK2, glucose transporter type 1 and
      hypoxia-inducible factor 1alpha. Compared with SW480 cells, the expression of
      cell cycle regulatory proteins was effectively inhibited in SW620 cells to
      sustain cell survival when there was a lack of energy. Furthermore, SW620 cells
      exhibited a stronger mesenchymal phenotype and stem cell characteristics compared
      with SW480 cells; CD133 and CD166 were highly expressed in SW620 cells, whereas
      expression was not detected in SW480 cells. These data may explain why metastatic
      cancer cells exhibit greater microenvironmental adaptability and survivability;
      specifically, this may be achieved by upregulating glycolysis, optimizing the
      cell cycle and reprogramming cell metabolism. The present study may provide a
      target metabolic pathway for cancer metastasis therapy.

PMID- 30280200
TI  - S100B regulates inflammatory response during osteoarthritis via fibroblast growth
      factor receptor 1 signaling.
AB  - The present study aimed to investigate the role of S100B in the inflammation
      process during osteoarthritis (OA). OA cartilage samples were collected for S100B
      expression analysis. S100B expression levels were significantly increased in
      patients with OA compared with the Controls (1.28+/-0.66 vs. 0.42+/-0.31; P=0.01)
      and were determined to be correlated with TNF-alpha (r=0.42; P=0.04) and IL-1beta
      (r=0.73; P=0.001) expression levels. Orthopedic casting tape was used to
      immobilize the right knee at 180 extension of adult female New Zealand white
      rabbits for 4 weeks to establish an OA model. Cartilage specimens from the medial
      femoral condyle of these rabbits were used for histological confirmation and
      immunohistochemical analyses, whereas synovial fluid was used in ELISA assays for
      tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta expression levels.
      Human synovial fibroblasts from the knee synovial tissues of normal patients with
      traumatic injury were transfected with S100B overexpression and knockdown
      plasmids and subjected to lipopolysaccharide (LPS) stimulation; subsequently, TNF
      alpha and IL-1beta expression levels in conditioned medium were determined by
      ELISA; S100B overexpression and knockdown significantly increased and decreased
      the TNF-alpha and IL-1beta expression levels, respectively. Increased TNF-alpha
      (573.3+/-15.4 vs. 102.6+/-8.7 pg) and IL-1beta (378.6+/-7.2 vs. 170.1+/-5.8 pg)
      expression levels were detected in OA model rabbits compared with the Control
      rabbits. Additionally, S100B, fibroblast growth factor (FGF)-1 and FGF receptor
      (FGFR)-1 mRNA and protein expression levels were increased in OA model rabbits
      compared with the Control group. FGFR1 knockdown significantly decreased TNF
      alpha and IL-1beta expression levels in LPS-stimulated S100B-overexpressing human
      synovial fibroblasts. S100B is involved in FGFR1 signaling-mediated inflammatory
      response during OA, which may be considered as a potential therapeutic target.

PMID- 30280202
TI  - Iliopsoas snapping hip: improving the diagnostic value of magnetic resonance
      imaging with a novel parameter.
AB  - OBJECTIVE: To illustrate an advanced imaging parameter that describes the course
      of the iliopsoas tendon, and evaluate its correlations with iliopsoas internal
      hip snapping syndrome. METHODS: This retrospective cohort study reviewed hip MRI
      images of all patients seen by a single surgeon between January 2015 and March
      2016. The comparison group included all patients with clinical internal hip
      snapping, versus the control group that did not. MRI images were processed using
      minimum intensity projection. Measurements obtained of the pelvis and course of
      the iliopsoas tendon included: pelvic incidence, coronal angle, and sagittal
      opening angle (SOA). Comparison of measurements between the groups was performed
      with Mann-Whitney U analysis and receiver operator curve (ROC) plotting, with a
      significance cutoff of p = 0.05. RESULTS: The control group (n = 85) and
      comparison group (n = 48) demonstrated no difference in age or gender. Pelvic
      incidence was similar [51.3 (+/- 10.7) degrees control versus 52.2 (+/- 7.7)
      degrees comparison (p = 0.36)], as was coronal angle [13.9 (+/- 4.6) degrees
      control versus 14.8 (+/-4.8) degrees comparison (p = 0.15)]. There was a
      significant difference in SOA [137.0 (+/- 5.9) degrees control versus 141.9 (+/-
      6.5) degrees comparison (p < 0.01)]. ROC analysis revealed SOA threshold of 140
      degrees for clinical IP hip snapping (p < 0.01), with odds ratio 5.2 (2.4-11.3)
      for SOA > 140 degrees. CONCLUSIONS: Iliopsoas hip snapping is often part of a
      more complex disease process. While challenging to diagnose, advanced imaging
      parameters, like the sagittal opening angle, relate with clinical pathology. The
      SOA offers diagnostic value, with a threshold of greater than 140 degrees
      significantly correlating with clinical presentation.

PMID- 30280203
TI  - Perioperative adverse events in women undergoing concurrent urogynecologic and
      gynecologic oncology surgeries for suspected malignancy.
AB  - INTRODUCTION AND HYPOTHESIS: This study's objectives were to compare the
      incidence of adverse events after concurrent urogynecologic and gynecologic
      oncology surgery to gynecologic oncology surgery alone and to describe the
      frequency of modification in planned urogynecologic procedures. The authors
      hypothesized there would be no difference in major complications. METHODS: This
      was a retrospective matched cohort study of women who underwent concurrent
      surgery at a large tertiary care center between January 2004 and June 2017.
      Cohorts were matched by surgeon, surgery route, date, and final pathologic
      diagnosis. Perioperative data and postoperative adverse events classified by
      Clavien-Dindo grade were compared. RESULTS: One hundred and eight patients
      underwent concurrent surgeries, with 216 matched cohorts. Concurrent-case
      patients were more likely to be older, postmenopausal, have greater vaginal
      parity, have had preoperative chemotherapy, and have preoperative cardiac or
      pulmonary disease. There were no differences in intraoperative complications or
      Dindo grade >= 3 adverse events between groups, but there were more grade 2
      adverse events in the concurrent cohort (44 vs 19%, p < 0.0001) including
      postoperative urinary tract infection (UTI) (26 vs 7%, p < 0.0001). Concurrent
      surgery remained associated with a higher incidence of grade >= 2 events on
      multivariate analysis [odds ratio (OR) 2.5, 95% confidence interval (CI) 1.5-4.2,
      p = 0.0004). Discharge with a urinary catheter was more frequent after concurrent
      cases (35 vs 2%, p < 0.0001). Planned urogynecologic procedures were modified in
      10% (n = 11) of cases. CONCLUSIONS: Concurrent surgeries have an increased
      incidence of minor but not serious perioperative adverse events. One in ten
      planned urogynecologic procedures is either modified or abandoned during combined
      surgeries.

PMID- 30280205
TI  - Tips and tricks for endoscopic negative pressure therapy.
AB  - Endoscopic negative-pressure therapy (ENPT) is becoming a valuable tool in
      surgical complication management of transmural intestinal defects and wounds in
      the upper and lower gastrointestinal tract. Innovative materials for drains have
      been developed, endoscopic techniques adapted, and new indications for ENPT have
      been found. Based on our broad clinical experience, numerous tips and tricks are
      described, which contribute to the safety of dealing with the new therapy. The
      aim of this work is to present these methods. The focus is on describing the
      treatment in the esophagus.

PMID- 30280204
TI  - [Preconditioning prior to visceral oncological surgery : A paradigm shift in
      visceral surgery?]
AB  - BACKGROUND: Postoperative complications after complex visceral oncological
      surgery can lead to substantial impairment of patients. In addition, preoperative
      physical performance and the severity of postoperative complications determine
      the long-term recovery process of physical function. Therefore, preconditioning
      in the preoperative period should be an important part of the
      preoperative/neoadjuvant treatment. OBJECTIVE: The aim of this article is a
      critical appraisal of current concepts of prehabilitation as well as their
      development potential and applicability in visceral surgery. MATERIAL AND
      METHODS: Based on a selective literature review, current studies and implemented
      concepts are presented and therapy algorithms are provided. RESULTS: This study
      differs in primary outcome, design and temporal framework of the intervention.
      The study results showed positive effects of an active increase in physical
      fitness in the preoperative period with respect to the quality of life,
      convalescence and postoperative pulmonary complication rate. DISCUSSION: In
      addition to the assessment of the individual risk of complications by means of
      spiroergometry, a targeted nutrition and exercise program can increase the
      individual performance level prior to visceral surgery and, thus, influence the
      postoperative risk of complications. The performance should be understood as a
      modifiable risk factor, which can also be positively influenced in the
      preoperative phase, even in a short time period. Individual preoperative care
      optimizes the physical and psychological situation of patients. To ensure the
      required individual care, approaches must be created and pursued, which can be
      implemented in a decentralized way.

PMID- 30280206
TI  - [Update on endocrine hypertension].
AB  - Endocrine disorders are the most common causes of secondary hypertension. Early
      diagnosis and specific treatment are crucial for improvement of the prognosis.
      This article provides an overview on which clinical constellations point to an
      increased risk of secondary causes of hypertension. These include spontaneous
      hypokalemia, young age at onset of hypertension, adrenal incidentaloma and
      therapy refractive arterial hypertension. The basic diagnostics include
      determination of the aldosterone to renin ratio, measurement of free plasma
      metanephrines and a 1 mg dexamethasone suppression test. Borderline results
      require repeated control testing and/or confirmatory testing under standardized
      test conditions. In cases of repeatedly conspicuous results referral to a
      specialized clinic should be considered for further clarification and
      confirmation of the diagnosis. Imaging diagnostics may constitute an adjunct to
      laboratory testing after the diagnosis has been confirmed. Therapeutic algorithms
      vary depending on the underlying endocrine disease.

PMID- 30280207
TI  - Twelve-year trend in the use of zolpidem and physicians' non-compliance with
      recommended duration: a Korean national health insurance database study.
AB  - OBJECTIVES: Abuse of zolpidem has sporadically been reported and little is known
      regarding nationwide patterns of zolpidem use in Korea. This study investigates
      the extent of zolpidem usage exceeding the recommended duration and the
      predictors. METHODS: We conducted a drug utilization study using the national
      sample cohort database of the Korea National Health Insurance Corporation between
      2002 and 2013. The study subjects were patients treated with zolpidem in the
      outpatient setting. An episode was defined as a period of continuous zolpidem
      therapy. The provider-based episode allowed for a gap of up to 3 days between two
      consecutive prescriptions from the same institution. The person-based episode
      allowed for a gap of up to 3 days, regardless of institution. We calculated the
      proportion of zolpidem use for periods over 30 days and conducted logistic
      regression analyses to investigate the relevant predictors. An adjusted odds
      ratio (aOR) with a 95% confidence interval (CI) was estimated for each predictor.
      RESULTS: The usage of zolpidem is dramatically increased by approximately 18
      times since zolpidem was authorized in the market (1181 in 2002 vs. 21,399 in
      2013). The treatment duration in 8.3% of episodes exceeded 30 days out of 75,087
      zolpidem users. The odds of zolpidem prescription exceeding 30 days were highest
      in patients aged 65 years and older (aOR = 2.13, 95% CI 1.78-2.53) and at
      tertiary hospitals (aOR = 2.14, 95% CI 1.68-2.72). Women were more likely than
      men to be treated with zolpidem for over 30 days. CONCLUSION: We found dramatic
      increase of zolpidem use from 2002 to 2013. In 8.3% of the prescribed episodes of
      zolpidem, the recommended duration was exceeded. Efforts are required to reduce
      prescriptions that are inconsistent with the recommended guidelines for older
      patients, women, and in tertiary hospitals.

PMID- 30280208
TI  - Non-steroidal anti-inflammatory drugs and risk of Parkinson's disease in the
      elderly population: a meta-analysis.
AB  - PURPOSE: Several studies have explored the impact of non-steroidal anti
      inflammatory drugs (NSAIDs) and the risk of Parkinson disease (PD). However, the
      extent to which NSAIDs may increase or decrease the risk of PD remains
      unresolved. We, therefore, performed a meta-analysis of relevant studies to
      quantify the magnitude of the association between NSAID use and PD risk in the
      elderly population. METHODS: The electronic databases such as PubMed, EMBASE,
      Scopus, Google Scholar, and Web of Science were used to search the relevant
      articles published between January 1990 and December 2017. Large (n >= 1000)
      observational design studies with a follow-up at least 1 year were considered.
      Two authors independently extracted information from the included studies. Random
      effect model was used to calculate risk ratios (RRs) with 95% confidence interval
      (Cl). RESULTS: A total of 17 studies with 2,498,258 participants and nearly
      14,713 PD patients were included in the final analysis. The overall pooled RR of
      PD was 0.95 (95%CI 0.860-1.048) with significant heterogeneity (I2 = 63.093, Q =
      43.352, p < 0.0001). In the subgroup analysis, the overall pooled RR of PD was
      0.90 (95%CI 0.738-1.109), 0.96 (95%CI 0.882-1.055), and 0.99 (95%CI 0.841-0.982)
      from the studies of North America, Europe, and Asia. Additionally, long-term use,
      study design, individual NSAID use, and risk of PD were also evaluated.
      CONCLUSION: Despite the neuroprotective potential of NSAIDs demonstrated in some
      experimental studies, our findings suggest that there is no association between
      NSAIDs and the risk of Parkinson disease at the population level. Until further
      evidence is established, clinicians need to be vigilant ensuring that the use of
      NSAIDs remains restricted to their approved anti-inflammatory and analgesic
      effect.

PMID- 30280209
TI  - [Focused sonography in orthopedic emergencies].
AB  - Focused sonography of the musculoskeletal system in the emergency room should be
      done for time-effective and symptom-oriented detection of suspected findings.
      Analogous to other point-of-care ultrasound in emergency medicine, it is by
      definition not a complete ultrasound examination of the respective organ (e.g.,
      shoulder, elbow). It allows detection of important findings (luxation, effusion,
      fracture or rupture) with good to excellent diagnostic accuracy. Afterwards
      computed tomography, magnetic resonance imaging or complete sonographic
      examination (according to the guidelines of the working group Bewegungsorgane der
      Deutschen Gesellschaft fur Ultraschall in der Medizin, which are identical to
      those of the working group Orthopadie und Unfallchirurgie) should be added as
      clinically required. Sonography of the musculoskeletal system in the emergency
      room can be performed on the lying or sitting patient, except when examining the
      shoulder, in which there is a difference. The interventional procedures are safe,
      useful and time saving.

PMID- 30280211
TI  - Assessment of the Australian Bureau of Meteorology wet bulb globe temperature
      model using weather station data.
AB  - Exertional heat illnesses affect thousands of athletes each year and are a
      leading cause of death in sports. The wet bulb globe temperature (WBGT) is widely
      used as a heat stress metric in athletics for adjusting activities. The WBGT can
      be measured on-site with portable sensors, but instrument cost may provide a
      barrier for usage. Modeling WBGT from weather station data, then, presents an
      affordable option. Our study compares two WBGT models of varying levels of
      sophistication: the Australian Bureau of Meteorology (ABM) model which uses only
      temperature and humidity as inputs and a physically based model by Liljegren that
      incorporates temperature, humidity, wind speed, and solar radiation in
      determining WBGT outputs. The setting for the study is 19 University of Georgia
      Weather Network stations selected from across the state of Georgia, USA, over a 6
      year period (2008-2014) during late summer and early fall months. Results show
      that the ABM model's performance relative to the Liljegren model varies based on
      time of day and weather conditions. WBGTs from the ABM model are most similar to
      those from the Liljegren model during midday when the assumption of moderately
      high sun most frequently occurs. We observed increasingly large positive biases
      with the ABM model both earlier and later in the day during periods with lower
      solar radiation. Even during midday, large (>= 3  degrees C) underestimates may
      occur during low wind conditions and overestimates during periods with high cloud
      cover. Such differences can lead to inaccurate activity modification and pose
      dangers for athletes either by underestimating heat-related hazards or by
      imposing an opportunity cost if practice activities are limited by overestimating
      the heat hazard.

PMID- 30280212
TI  - Valuation of the human thermal discomfort index for the five Brazilian regions in
      the period of El Nino-Southern Oscillation (ENSO).
AB  - Brazil is an extensive country with five administrative regions that have
      different climates, mainly due to their geographic locations. The El Nino
      Southern Oscillation influences the regime of temperature and precipitation of
      the Brazilian regions, which can directly affect the thermal discomfort of the
      population. The objective of this study was to evaluate the human thermal
      discomfort index (HDI) in the five regions of Brazil for El Nino, La Nina, and
      neutral years from 1979 to 2017, as well as the influence of the degree of
      intensity of the Pacific Ocean anomaly in the thermal conditions of the Brazilian
      regions. Monthly data on air temperature and dewpoint temperature obtained from
      the ERA-Interim reanalysis were used. The HDI was calculated using specific
      equations. The results were analyzed by means of composition fields. From the
      results, it was possible to conclude that the El Nino and La Nina phenomena
      influence the HDI of the Brazilian regions. El Nino increases the discomfort due
      to the heat and the La Nina causes them to decrease. This study is important
      since these phenomena, by influencing thermal conditions, directly affect the
      well-being and health of the Brazilian population.

PMID- 30280213
TI  - Treatment of steroid-resistant nephrotic syndrome in the genomic era.
AB  - The pathogenesis of steroid-resistant nephrotic syndrome (SRNS) is not completely
      known. Recent advances in genomics have elucidated some of the molecular
      mechanisms and pathophysiology of the disease. More than 50 monogenic causes of
      SRNS have been identified; however, these genes are responsible for only a small
      fraction of SRNS in outbred populations. There are currently no guidelines for
      genetic testing in SRNS, but evidence from the literature suggests that testing
      should be guided by the genetic architecture of the disease in the population.
      Notably, most genetic forms of SRNS do not respond to current immunosuppressive
      therapies; however, a small subset of patients with monogenic SRNS will achieve
      partial or complete remission with specific immunomodulatory agents, presumably
      due to non-immunosuppressive effects of these agents. We suggest a pragmatic
      approach to the therapy of genetic SRNS, as there is no evidence-based algorithm
      for the management of the disease.

PMID- 30280214
TI  - Expression profiles of pro-inflammatory and pro-apoptotic mediators in secondary
      tethered cord syndrome after myelomeningocele repair surgery.
AB  - PURPOSE: The literature on histopathological and molecular changes that might
      underlie secondary tethered cord syndrome (TCS) after myelomeningocele (MMC)
      repair surgeries remains sparse. To address this problem, we analyzed specimens,
      which were obtained during untethering surgeries of patients who had a history of
      MMC repair surgery after birth. METHODS: Specimens of 12 patients were analyzed
      in this study. Clinical characteristics were obtained retrospectively including
      pre-operative neurological and bowel/bladder-function, contractures and
      spasticity of lower extremities, leg and back pain, syringomyelia, and conus
      position on spinal MRI. Cellular marker expression profiles were established.
      Further, immunoreactivities (IR) of IL-1beta/IL-1R1, TNF-alpha/TNF-R1, and HIF
      1alpha/-2alpha were analyzed qualitatively and semi-quantitatively by
      densitometry. Co-labeling with cellular markers was determined by multi
      fluorescence-labeling. Cytokines were further analyzed on mRNA level.
      Immunostaining for cleaved PARP and TUNEL was performed to detect apoptotic
      cells. RESULTS: Astrocytosis, appearance of monocytes, activated microglia, and
      apoptotic cells in TCS specimens were one substantial finding of these studies.
      Besides neurons, these cells co-stained with IL-1beta and TNF-alpha and their
      receptors, which were found on significantly elevated IR-level and partially mRNA
      level in TCS specimens. Staining for HIF-1alpha/-2alpha confirmed induction of
      hypoxia-related factors in TCS specimens that were co-labeled with IL-1beta.
      Further, hints for apoptotic cell death became evident by TUNEL and PARP-positive
      cells in TCS neuroepithelia. CONCLUSIONS: Our studies identified pro-inflammatory
      and pro-apoptotic mediators that, besides mechanical damaging and along with
      hypoxia, might promote TCS development. Besides optimizing surgical techniques,
      these factors should also be taken into account when searching for further
      options to improve TCS treatment.

PMID- 30280215
TI  - Risk factors for refracture of the forearm in children treated with elastic
      stable intramedullary nailing.
AB  - PURPOSE: This study aims to investigate risk factors for refracture of the
      forearm in children treated with elastic stable intramedullary nailing (ESIN).
      METHODS: Clinical data of 267 patients who had been treated for forearm fractures
      by ESIN in our hospital from January 2010 to December 2014 were retrospectively
      reviewed. Risk factors for forearm refractures were determined using logistic
      regression analysis. RESULTS: Forearm refractures occurred in 11 children.
      Univariate analysis revealed that age, body weight, number of fractures, open
      fracture, nail diameter, and immobilization time were not associated with
      refractures. However, gender (male, P = 0.042) and fracture location (lower
      third, P = 0.007) were significantly associated with refractures. Multivariate
      analysis revealed that fracture location was an independent risk factor for
      forearm refractures (P = 0.031). CONCLUSION: Forearm refracture is uncommon in
      children treated with ESIN. Fracture location is an independent risk factor for
      forearm refractures in these patients.

PMID- 30280216
TI  - Induced membrane technique for the treatment of severe acute tibial bone loss:
      preliminary experience at medium-term follow-up.
AB  - PURPOSE: Management of acute open tibial fractures with critical bone defect
      remains a challenge in trauma surgery. Few and heterogeneous cases have been
      reported about the treatment with the induced membrane technique. METHODS: We
      prospectively evaluated three patients treated with the induced membrane
      technique for acute Gustilo IIIB tibial fractures with critical bone defect.
      Success treatment was defined by bone union with patient pain free. Clinical and
      radiological evaluations were performed regularly until healing, then annually
      and with a minimum follow-up of five years. RESULTS: In all patients but one, a
      success was recorded, respectively, at four and six months. These two patients
      were pain free until the final follow-up, and no graft resorption or secondary
      complications related to the index surgery were observed. The third case was
      managed successfully with a bone transport technique. CONCLUSION: The induced
      membrane technique is an alternative good option for the treatment of these
      severe lesions.

PMID- 30280217
TI  - Computed tomography evaluation of total knee arthroplasty implants position after
      two different surgical methods of implantation.
AB  - PURPOSE: The objectives of this study were to determine the reliability of a
      novel method of measuring the rotational alignment of an anatomical tibial tray,
      the difference in the rotational alignment of the femoral and tibial component
      according to pure measured resection or blended technique with tensor, and,
      finally, the difference in terms of clinical results according to the two
      different methods. PATIENTS AND METHODS: We performed a total of 60 consecutive
      TKAs: 30 according to pure measured resection and 30 according to blended
      technique with tensor (FuZion(r)). Clinical scores and CT scan were done at six
      months to measure patient's outcome and prosthetic components rotation. RESULTS:
      The method of measurement of tibial tray had high agreement between different
      radiological observers. Mean external rotation alignment of the femur was 2.7
      degrees  in standard group and 0.5 degrees  in the FuZion(r) group. For all
      clinical indices, we observed a large and significant improvement at follow-up,
      better in blended technique group, but without a clear superiority, and no
      statistically significant difference was evident between the two groups. At
      follow-up, HSS was to 89.7 in the FuZion(r) group and 89.0 in the standard group,
      KSS (clinical) was 92.6 in and 91.3 respectively, and KSS (Functional) was 91.0
      in the FuZion(r) group and 87.6 in the standard group. CONCLUSIONS: Our CT
      measurement method is reliable and reproducible. All patients operated with this
      personalized knee system design obtained excellent results; the customization of
      femoral rotation with a blended technique is, probably, the key to optimize the
      outcomes and achieve the state of forgotten knee.

PMID- 30280218
TI  - Preliminary results of autologous adipose-derived stem cells in early knee
      osteoarthritis: identification of a subpopulation with greater response.
AB  - PURPOSE: The purpose of this study was to report the clinical and functional
      results of a series of patients with early knee osteoarthritis (KOA) treated with
      the intra-articular injection of autologous adipose-derived stem cells (aASCs)
      plus arthroscopic debridement. The hypothesis was that protocol would
      significantly improve the clinical and functional outcomes in patients with early
      KOA. METHODS: Fifty-two patients with early KOA, who received arthroscopic
      debridement followed by percutaneous injection of aASCs, were enrolled into the
      study and retrospectively analyzed with an average follow-up of 15.3 (range, 6 to
      24) months. Patients were assessed through the IKS knee and function scores and
      VAS pain scale. RESULTS: The mean IKS knee score improved from 37.4 (range, 14 to
      79) points pre-operatively to 62.6 (range, 27 to 95) points at the latest follow
      up (p < < 0.01). The mean IKS function score improved from 57.2 (range, 25 to
      100) points pre-operatively to 83.0 (range, 35 to 100) points at the latest
      follow-up (p < < 0.01). The mean VAS score decreased from 8.5 (range, 3 to 10)
      pre-operatively to 5.1 (range, 0 to 8) at the latest follow-up (p < < 0.01).
      Additionally, patients with a pre-operative VAS score greater than 8 were found
      to show greater clinical and functional benefits compared with patients with VAS
      score lower than 8. CONCLUSIONS: The knee injection of aASCs associated to
      arthroscopic debridement increased significantly the clinical and functional
      scores in patients with early KOA at a mid-term follow-up, especially those with
      higher pre-operative VAS scores.

PMID- 30280219
TI  - Two cases of subcutaneous dirofilariasis in Barcelona, Spain.
AB  - In recent years, the number of reported cases of human dirofilariasis in Europe
      has increased and the circulation of Dirofilaria spp. in mosquitoes in several
      European countries has been proven. We report here two likely autochthonous cases
      of subcutaneous human dirofilariasis from Barcelona, Spain, caused by Dirofilaria
      repens. The potential for an increase in human infection is high given the number
      of cases published recently and the ability of vectors to spread through the
      Mediterranean basin.

PMID- 30280221
TI  - Intrahepatic Balloon Tamponade for Penetrating Liver Injury: Rarely Needed but
      Highly Effective.
AB  - BACKGROUND: Severe penetrating liver injuries are associated with high rates of
      morbidity and mortality. The objective of this study was to demonstrate the 15
      year experience of a Level 1 US trauma center with use of intrahepatic balloon
      tamponade for penetrating liver injuries in adult patients. METHODS: Operative
      notes were used to identify cases employing intrahepatic balloon tamponade.
      Charts were reviewed for patient characteristics, injury characteristics,
      morbidity, and in-hospital mortality. RESULTS: Of the 4961 penetrating trauma
      patients admitted during the study period, 279 (5.6%) had liver injury and
      underwent exploratory laparotomy. Intrahepatic balloon tamponade was attempted in
      nine patients (3.2%). Two of the nine patients (22%) were in cardiac arrest at
      time of balloon placement and died during the index operation; both had
      retrohepatic IVC injury combined with cardiopulmonary injury. In patients who
      reached the operating room alive and had spontaneous circulation at the time of
      balloon placement, utilization of this technique was associated with 100%
      survival. CONCLUSION: Although rarely needed, trauma surgeons must be prepared to
      use intrahepatic balloon tamponade as one surgical technique to control major
      hepatic injuries.

PMID- 30280222
TI  - Relationships Between Expertise, Crew Familiarity and Surgical Workflow
      Disruptions: An Observational Study.
AB  - BACKGROUND: Teamwork is an essential factor in reducing workflow disruption (WD)
      in the operating room. Team familiarity (TF) has been recognized as an antecedent
      to surgical quality and safety. To date, no study has examined the link between
      team members' role and expertise, TF and WD in surgical setting. This study aimed
      to examine the relationships between expertise, surgeon-scrub nurse familiarity
      and WD. METHODS: We observed a convenience sample of 12 elective neurosurgical
      procedures carried out by 4 surgeons and 11 SN with different levels of expertise
      and different degrees of familiarity between surgeons and SN. We calculated the
      number of WD per unit of coding time to control for the duration of operation. We
      explored the type and frequency of WD, and the differences between the surgeons
      and SN. We examined the relationships between duration of WD, staff expertise and
      surgeon-scrub nurse familiarity. RESULTS: 9.91% of the coded surgical time
      concerned WD. The most frequent causes of WD were distractions (29.7%) and
      colleagues' interruptions (25.2%). This proportion was seen for SN, whereas
      teaching moments and colleagues' interruptions were the most frequent WD for
      surgeons. The WD was less high among expert surgeons and less frequent when
      surgeon was familiar with SN. CONCLUSIONS: The frequency of WD during surgical
      time can compromise surgical quality and patient safety. WD seems to decrease in
      teams with high levels of surgeon-scrub nurse familiarity and with development of
      surgical expertise. Favoring TF and giving feedback to the team about WD issues
      could be interesting ways to improve teamwork.

PMID- 30280220
TI  - The potential effects of silver and gold nanoparticles as molluscicides and
      cercaricides on Schistosoma mansoni.
AB  - Schistosomiasis seriously affects human health in tropical regions. Its
      prevention is more important than treatment, raising the need for effective
      control methods. Recently, the role of nanomaterials in medical science has been
      growing. The present study aimed to evaluate the potential effects of silver (Ag)
      and gold (Au) nanoparticles (NPs) on Biomphalaria alexandrina snails and
      Schistosoma mansoni cercariae in vitro and to assess their effects on the
      infectivity of cercariae in vivo. The in vitro study proved that Ag and Au NPs
      were effective in killing B. alexandrina snails, with 30 MUg/ml Ag and 160 MUg/ml
      Au causing 100% mortality. The LC50 of 9.68 MUg/ml for Ag NPs and 133.7 MUg/ml
      for Au NPs prevented snail infection with S. mansoni miracidia. Furthermore, Ag
      NPs at 50 MUg/ml and Au NPs at 100 MUg/ml increased the mortality of S. mansoni
      cercariae in a dose- and time-dependent manner, reaching 100% mortality after 1
      h. The in vivo study found that Ag NPs prevented the occurrence of infection when
      cercariae were treated before the infection by either the tail immersion (TI) or
      subcutaneous (SC) route, as proven by parasitological parameters and by the
      absence of granuloma formation in hepatic tissue. Meanwhile, infection of mice by
      untreated cercariae followed by treatment with NPs 1 h post-infection (PI) caused
      a decrease in egg count/g intestine and egg count/g liver in the TI-infected
      group only. The oogram patterns and granuloma formation results were similar
      between infection control and the SC-infected group. On the other hand, Au NPs
      led to a decrease in total worm burden (TWB) in all tested groups, with a
      decrease in egg count/g intestine and egg count/g liver in TI-infected groups
      with either pre-treated or post-treated cercariae, in contrast to SC-infected
      groups. However, the oogram patterns and granuloma formation showed similar
      results to infection control. Ag and Au NPs have potential as molluscicides and
      cercaricides in vitro and can prevent or modulate the infectivity of cercariae in
      vivo.

PMID- 30280223
TI  - Correction to: Fecal calprotectin is not a clinically useful marker for the
      prediction of the early nonresponse to exclusive enteral nutrition in pediatric
      patients with Crohn disease.
AB  - This article was originally published with all author names incorrectly listed.
      All author names have now been transposed and appear correctly above. The
      original article was corrected.

PMID- 30280224
TI  - Are mechanical and chemical trauma the reason of meatal stenosis after newborn
      circumcision?
AB  - : Mechanical and chemical trauma are a widely accepted theories to explain the
      pathogenesis of meatalstenosis after newborn circumcision. The aim of the present
      study was to explore the theory that an exposed glans is prone to meatal
      stenosis. This was done by a novel investigation of boys who were born with
      "hooded prepuce", a condition in which the glans is completely exposed. Physical
      examination, lower urinary tract symptoms, urethral meatus configuration, and
      surgical procedures of 18 children admitted for routine circumcision, who had
      congenital hooded prepuce with normally located urethral meatus, were analyzed.
      The study period was 2013 and 2018. All the cases have been seen because of
      neonatal circumcision request, but was postponed due to hooded prepuce. The only
      presenting complaint in children was a cosmetically unattractive appearance.
      There were no symptoms associated with meatal stenosis, they circumcised in an
      average of 6 years and non of them required any additional procedure. CONCLUSION:
      Meatal stenosis did not occur in cases whose glans penis are naked with hooded
      prepuce. These findings do not support the default chemical and mechanical trauma
      theories. Hooded prepuce without any penile anomalies is only a cosmetically
      unattractive appearance and circumcision can correct this. What is known: * The
      common theory of meatal stenosis etiology is that the meatus undergoes irritation
      with chemical/mechanical trauma in the absence of a prepuce after newborn
      circumcision. * Circumcision is usually postponed in newborns with hooded
      prepuce. What is new: * We did not notice meatal stenosis in cases whose urethral
      meatus were not covered with a prepuce congenitally. Ammoniacal dermatitis or
      mechanical trauma theories may not explain the cause of meatal stenosis. * Hooded
      prepuce is not a handicap to newborn circumcision. It is just a cosmetic problem
      and circumcision can solve it.

PMID- 30280226
TI  - High-affinity graphene oxide-encapsulated magnetic Zr-MOF for pretreatment and
      rapid determination of the photosensitizers hematoporphyrin and hematoporphyrin
      monomethyl ether in human urine prior to UPLC-HRMS.
AB  - In this paper, a high-affinity graphene oxide-encapsulated magnetic Zr-MOF (GO
      Mag@Zr-MOF) was synthesized and characterized by SEM, TEM, and XPS for its
      morphology, structure, and components. Subsequently, the as-prepared GO-Mag@Zr
      MOF was, for the first time, employed as magnetic solid-phase extraction (MSPE)
      adsorbent for pretreatment and determination of photodynamic therapy (PDT) with
      the photosensitizers hematoporphyrin (Hp) and hematoporphyrin monomethyl ether
      (HMME) in human urine samples coupled with ultra-performance liquid
      chromatography-high resolution mass spectrometry (UPLC-HRMS). The synthesized GO
      Mag@Zr-MOF revealed excellent adsorption efficiency for Hp and HMME in urine
      samples. Under optimal conditions, the spiked recoveries of the developed method
      were in the range of 89.5-105.6% with RSDs less than 10%. The limits of detection
      (LODs) were found to be 0.036 and 0.042 MUg/L for Hp and HMME, respectively,
      while limits of quantitation (LOQs) were 0.12 and 0.14 MUg/L. The proposed method
      was found to be rapid, effective, sensitive, and accurate for clinical analysis.
      Moreover, this paper, for the first time, carefully expounded the mass spectrum
      cracking mechanisms of Hp and HMME. Graphical abstract ?.

PMID- 30280225
TI  - Direct bacteria analysis using laserspray ionization miniature mass spectrometry.
AB  - An atmospheric pressure laserspray ionization mass spectrometry (AP-LSI mini MS)
      has been developed and employed in the fast analysis of bacteria. Without using
      surfactants or any extracting methods, 21 foodborne bacteria from 12 genera were
      directly analyzed. Typical fingerprints of small molecules and lipids were
      detected and recognized in the mass spectra with high reproducibility.
      Furthermore, a supervised multivariate statistics method, orthogonal partial
      least squares (OPLS), was applied, and these bacteria could be differentiated at
      both genus and species levels. With improved performance in the future, AP-LSI
      mini MS could be a simple, effective, and fast approach for direct bacteria
      analysis on the field.

PMID- 30280227
TI  - Development and validation of an LC-MS/MS assay for the quantification of
      dolutegravir extracted from human hair.
AB  - Measurement of drug concentrations in hair provides a non-invasive approach to
      assess drug adherence. Here, we report on the development and validation of a
      method for the quantification of the antiretroviral dolutegravir (DTG) extracted
      from human hair. DTG is extracted from hair samples by sonication and incubation
      in 50:50 methanol:acetonitrile with 2% formic acid overnight at 40  degrees C.
      Following extraction, samples are analyzed by reverse-phase chromatography on a
      Waters Atlantis T3 (50 * 2.1 mm, 3-MUm particle size) column with subsequent
      detection by electrospray ionization in positive ion mode on an AB Sciex API-5000
      triple quadrupole mass spectrometer. The stable, isotopically labeled 13C,d5-DTG
      is used as an internal standard in the assay. The calibration range is 5-10,000
      pg DTG/mL of extraction solvent with the ability to extract between 1 and 10 mg
      of hair/mL of extraction solvent. The assay was linear, accurate (inter-assay
      %bias within +/- 6.5%), and precise (inter-assay %CV <= 10.3%). The assay was
      successfully used to analyze clinical samples from subjects on DTG regimens.
      Analysis of clinical samples suggested the potential presence of a degradation
      product, which was subsequently confirmed to occur with exposure to sunlight. The
      degradation of DTG could complicate absolute interpretation of clinical results,
      but the presence of this degradation product is easily evaluated with this assay
      to aid in data interpretation.

PMID- 30280228
TI  - Portable glucose meter: trends in techniques and its potential application in
      analysis.
AB  - A blood glucose meter is an electronic medical device used for determining the
      concentration of glucose in blood. These meters have undergone five phases of
      development: washed blood glucose meters, wiped blood glucose meters,
      colorimetric blood glucose meters, electrochemical blood glucose meters, and
      micro, multiple site blood glucose meters. Thanks to their speed, portability,
      low cost, and easy operation, blood glucose meters have been widely available for
      use in clinical diagnosis. Recently, coupling of target recognition elements
      (antibody-antigen recognition, nucleic acid hybridization, enzyme recognition,
      and click chemistry) with signal transduction and amplification strategies
      (glucose-generating enzymes, nicotinamide adenine dinucleotide (NADH)-generating
      enzymes, encapsulated glucose, nanomaterials, and cyclic amplification of DNA)
      has allowed various targets to be determined via the relationship between the
      signal of the blood glucose meter and the concentration of targets. In this
      paper, a brief review of the development and mechanism of blood glucose meters is
      given first. Then, more details on the application of blood glucose meters in
      analysis are described, including biomedical analysis, food analysis, and
      environmental analysis. Finally, the prospect of future development of blood
      glucose meters is also discussed. Graphical abstract ?.

PMID- 30280229
TI  - Drosophila melanogaster odorant receptors as volatile compound detectors in
      forensic science: a proof-of-concept study.
AB  - The ability to detect and identify substances based on the volatile compounds
      (odors) they emit is relied upon heavily for numerous investigative purposes.
      Animals have an innate olfactory sensitivity and selectivity that out-performs
      current instrumentation. This has led to immense interest in their employment as
      chemical sensors for a range of applications, including forensic science, both as
      whole organisms and as sensing elements in biosensors. Using electrophysiological
      and calcium imaging assays, this research examined the response of Drosophila
      melanogaster olfactory receptors (ORs) to odor compounds significant in forensic
      science and assessed their potential utility as volatile compound sensors. This
      investigation illustrated the different sensitivities, selectivities, and sensing
      features of individual ORs and demonstrated that their employment for detection
      purposes is feasible. While further research expanding on this study will be
      required to demonstrate the performance characteristics that an OR-based
      detection system will ultimately possess, this research provides an encouraging
      first step towards the goal of utilizing isolated biological ORs as volatile
      compound sensors in forensic science.

PMID- 30280231
TI  - [Systematic literature search in PubMed : A short introduction].
AB  - In order to identify current (and relevant) evidence for a specific clinical
      question within the unmanageable amount of information available, solid skills in
      performing a systematic literature search are essential. An efficient approach is
      to search a biomedical database containing relevant literature citations of study
      reports. In this article, we explain step by step how to perform a systematic
      literature search via PubMed (MEDLINE) by means of an example research question
      in the field of ophthalmology. First, we demonstrate how to translate the
      clinical problem into a well-framed and searchable research question, how to
      identify relevant search terms and how to conduct a text word search and a search
      with keywords in MeSH terms. We then show how to limit the number of search
      results if the search yields too many irrelevant hits and how to increase the
      number in the case of too few citations. Finally, we summarize all essential
      principles that guide a literature search via PubMed.

PMID- 30280230
TI  - Preparation and characterization of large-format macroporous cryogel disks for
      use in affinity chromatography and biotechnological applications.
AB  - We have prepared and evaluated larger format phage-bound epoxy-cryogel columns in
      order to increase the yield of bound target. Freezing thermograms showed that
      larger column formats (2.5-5 cm diameter) are not usable due to irregular
      polymerization phenomena. Preparing thin disks of 0.5 cm height with similar
      diameter proved to be an excellent alternative. Disks could be stacked and run in
      a chromatographic setup. In this way, we could increase the matrix volume, ligand
      binding capacity, and finally the yield of bound target. By increasing the column
      volume about sevenfold, we observed a 12-fold increase of ligand density and a
      sevenfold increase in the yield of protein recovery in a column where phages were
      attached without spacer and a 10- to 34-fold increase in a spacer column,
      depending on the spacer used.

PMID- 30280232
TI  - [Update DVO guidelines 2017 on "Prophylaxis, diagnostics and treatment of
      osteoporosis in postmenopausal women and men" : What is new, what remains for
      rheumatologists?]

PMID- 30280233
TI  - [Differential diagnostics of lipedema and lymphedema : A practical guideline].
AB  - Lipedema is a symmetrical disorder of the subcutaneous adipose tissue that
      affects almost exclusively women in postpubescent age. The trinity of disfiguring
      hyperplastic adipose tissue of the proximal extremities, increasing pain over
      time and bruising is characteristic. Lymphedema can occur in both sexes and is
      differentiated into primary and secondary subtypes. Symmetry is not a
      prerequisite for diagnosis. Characteristic for lymphedema is the disproportion
      between lymphatic fluid and the capacity of lymphatic vessels. The most distal
      body parts are always more severely affected than proximal parts. In the initial
      phases lymphedema is painless but in advanced stages tension pain can occur. The
      combination of both disorders has been described; however, lipedema is not
      responsible for subsequent lymphedema in contrast to central obesity, which
      significantly increases the risk of lymphedema. The differential diagnosis is of
      utmost importance for a meaningful management.

PMID- 30280234
TI  - Phenotyping Thermal Responses of Yeasts and Yeast-like Microorganisms at the
      Individual and Population Levels: Proof-of-Concept, Development and Application
      of an Experimental Framework to a Plant Pathogen.
AB  - Deciphering the responses of microbial populations to spatiotemporal changes in
      their thermal environment is instrumental in improving our understanding of their
      eco-evolutionary dynamics. Recent studies have shown that current phenotyping
      protocols do not adequately address all dimensions of phenotype expression.
      Therefore, these methods can give biased assessments of sensitivity to
      temperature, leading to misunderstandings concerning the ecological processes
      underlying thermal plasticity. We describe here a new robust and versatile
      experimental framework for the accurate investigation of thermal performance and
      phenotypic diversity in yeasts and yeast-like microorganisms, at the individual
      and population levels. In addition to proof-of-concept, the application of this
      framework to the fungal wheat pathogen Zymoseptoria tritici resulted in detailed
      characterisations for this yeast-like microorganism of (i) the patterns of
      temperature-dependent changes in performance for four fitness traits; (ii) the
      consistency in thermal sensitivity rankings of strains between in planta and in
      vitro growth assessments; (iii) significant interindividual variation in thermal
      responses, with four principal thermotypes detected in a sample of 66 strains;
      and (iv) the ecological consequences of this diversity for population-level
      processes through pairwise competition experiments highlighting temperature
      dependent outcomes. These findings extend our knowledge and ability to quantify
      and categorise the phenotypic heterogeneity of thermal responses. As such, they
      lay the foundations for further studies elucidating local adaptation patterns and
      the effects of temperature variations on eco-evolutionary and epidemiological
      processes.

PMID- 30280235
TI  - [Biologics and further new drugs for rheumatic diseases since 2000].
AB  - BACKGROUND: Rheumatoid arthritis (RA), psoriatic arthritis and axial
      spondyloarthritis are severe diseases, which without adequate treatment lead to
      extremely reduced mobility, functional status and quality of life. OBJECTIVE: The
      effects of biologics and further new antirheumatic drugs on the burden of
      disease. METHODS: Evaluation of study results and register data dealing with the
      efficacy and safety of these drugs. RESULTS: Biologics have been proven to
      dramatically improve the outcome of all three diseases and contributed to the
      fact that remission is a realistic target today. In addition, the cardiovascular
      risk and mortality in RA have been reduced and structural damage is considerably
      blocked by biologics. Recently Janus kinase (JAK) inhibitors contributed to the
      treatment possibilities in the same way. Biologics as well as JAK inhibitors
      offer an excellent safety profile and tolerability with infections being the most
      important risk. CONCLUSION: With the availability of biologics and additional new
      drugs all three diseases have lost the status of difficult to treat diseases.
      Their usage according to the guidelines ensures that the burden of disease can
      been minimalized in most cases. The benefit-risk profile of these drugs has been
      shown to be excellent.

PMID- 30280236
TI  - Zoledronic acid : Treatment option for Gorham-Stout disease.
AB  - Gorham-Stout disease is a rare bone resorption disease, the etiology and
      prognosis of which is uncertain but it is thought to be benign. It can involve
      one or more bones and can cause pain, swelling, deformity and fractures in
      affected bones. Diagnosis is made with a combination of clinical, radiological
      and histopathological examinations once other causes of osteolysis have been
      excluded. Due to its rarity, there is no standard therapeutic approach.

PMID- 30280237
TI  - Gender differences in paid employment after retirement : Psychosocial working
      conditions and well-being.
AB  - BACKGROUND: An increasing number of persons continue to work after retirement
      age. This decision is often different between men and women as well as working
      histories, sectors and hierarchical positions; however, whether gender
      differences in working conditions and occupational well-being also exist in paid
      employment after retirement (PEAR) has not yet been investigated. OBJECTIVE: This
      study aimed to examine gender differences in working conditions and well-being of
      workers in PEAR. MATERIAL AND METHODS: In this study 784 employees (23.5% female)
      aged 65 years and older who were contracted by a Dutch temporary employment
      agency, participated in the baseline survey in 2011. Furthermore, a panel of 228
      employees (25.9% female) participated again during a second wave in 2012. Job
      demands, job control, emotional exhaustion and job engagement were assessed at
      both time points by validated self-reporting measures. RESULTS: Female employees
      worked fewer years in paid employment before 65 years of age, were more likely to
      be single, divorced or widowed, had a smaller income and worked less hours during
      PEAR than men. In the baseline analysis, females reported less job control and
      higher job stress than men. No gender differences were found on emotional
      exhaustion, engagement or job demands. Over the study period emotional exhaustion
      only increased in females. The longitudinal trend of job demands, control and
      engagement did not significantly differ between both sexes. CONCLUSION: The
      results suggest that working conditions of PEAR are less favorable for women than
      for men. Furthermore, the longitudinal trend of emotional exhaustion seems to be
      more disadvantageous for women.

PMID- 30280238
TI  - [Development and validation of the Mini Dental Assessment : A procedure for
      improved estimation of need for dental treatment in geriatrics].
AB  - BACKGROUND: In the future there will be an increasing demand for professional
      care with simultaneous retention of the dentition in older people. Due to
      inadequate dental knowledge, it is often not possible for caregivers to
      adequately assess dental deficits. OBJECTIVE: The aim of the study was to develop
      and validate a simple tool (Mini Dental Assessment, MDA) to assess possible
      dental treatment needs (DTN) of residential geriatric facilities by nursing
      personnel. MATERIAL AND METHODS: In the study 169 patients (51 from the
      University Hospital Giessen, 118 from the Bonifatius Hospital Lingen) underwent a
      dental examination. The dental status was evaluated based on the California
      Dental Association (CDA) criteria and the DTN determined. In addition, the time
      since the patients last visit to a dentist (TLVD) and denture age (DA) were
      documented and a chewing function test (carrot eating test, CET) was carried out.
      In a second study 155 patients were examined (115 from the University Hospital
      Giessen, 40 from the Bonifatius Hospital Lingen) corresponding to the reference
      sample and including a further chewing function test (after Schimmel und
      Slavicek) and questionnaires on quality of life (Oral Health Impact Profile
      (OHIP), Denatl Impact on Daily Living (DiDDL)). RESULTS: A total of 108 patients
      required dental treatment. The mean value (+/-SD) for the TLVD was 2.5 +/- 3.8
      years and 10.8 +/- 8.9 years for the DA. There was a positive correlation
      (Spearman, P < 0.005) between the DTN and degree of comminution in the CET (3.4
      +/- 1.8 grade). Based on the results an assessment tool was developed using the
      variables CET, TLVD and DA weighted by the respective regression coefficients
      (10:3:1). The resulting mean total MDA score was 51.32 +/- 28.14. A
      sensitivity/specificity analysis was conducted and a receiver operating
      characteristic (ROC) curve calculated (area under curve, AUC: 0.805; 95% CI:
      0.738-0.873). The ROC curve from the follow-up study showed a good agreement with
      the ROC curve from the reference study (AUC 0.829, 95% CI: 0.751-0.907).
      CONCLUSION: Based on the results of the study it could be shown that the MDA is a
      suitable instrument for making a valid statement on the assessment of DTN of
      patients in long-term care facilities. The validation study revealed the validity
      of the MDA in its originally developed form and the addition of two further
      chewing function tests did not significantly improve the validity of the MDA.
      Overall, the MDA appears to be an appropriate tool to help nursing home personnel
      to assess the necessity for nursing home residents to visit a dentist.

PMID- 30280239
TI  - Transition to retirement in the healthcare sector : Working conditions and
      attitudes of older workers.
AB  - BACKGROUND: The aging of societies will increase the need for healthcare services
      and lead to a growing number of older employees. These two developments are
      relevant in the healthcare sector (HCS), which is of rising societal and economic
      importance and at the same time employs many older people. OBJECTIVE: This
      article, which was written within the EXTEND project, investigates the working
      conditions and the prospective retirement age of older employees in the HCS in
      comparison to other sectors and explores what companies are doing to address the
      needs of this group. MATERIAL AND METHODS: The analysis was conducted as a mixed
      methods approach. The quantitative part was based on data derived from the
      Transitions and Old Age Potential (TOP) study in which older German employees
      were asked about their working conditions and retirement transitions. Matching
      techniques (coarsened exact matching) were used to investigate differences
      between sectors. The sample consisted of 114 employees aged between 55 and 65
      years, working in the HCS and their statistical twins. The qualitative analysis
      was based on case studies in two inpatient care organizations and two hospitals
      in Germany. A total of 23 semistructured interviews with staff members and with
      representatives of the management were carried out and thematically analyzed.
      RESULTS: The results showed that older employees in the HCS do not expect to
      retire earlier but preferred to do so significantly more often. Furthermore, HCS
      employees are more likely to face physically burdensome working conditions than
      in other sectors of the economy. The case studies indicated that there are very
      diverse and unsystematic strategies in addressing and supporting older employees.
      DISCUSSION: Older employees in the HCS sector are employed in much harsher
      working conditions than their peers in other sectors. This must be kept in mind
      when trying to extend their working lives.

PMID- 30280240
TI  - [Vertical and horizontal social inequality and motivation for early retirement].
AB  - BACKGROUND: Over the course of the demographic transition with an aging and
      shrinking work force, work participation of older employees becomes more and more
      important. Earlier investigations found social groups to be different in work
      related and individual aspects, which were shown to be associated with motivation
      for early retirement. OBJECTIVE: The aim of the study was to investigate the
      differences between older employees from distinct social groups in the motivation
      and determinants for early retirement. MATERIAL AND METHODS: Within the framework
      of the prospective lidA cohort study ( www.lida-studie.de ) socially insured
      employees born in 1959 and 1965 were asked about work, health and work
      participation. Based on data from the 3961 participants who were employed at the
      time of both study waves (2011, 2014), associations between variables of
      horizontal (gender, migration background) and vertical (education) social
      inequality and motivation for early retirement were analyzed with multiple
      logistic regression and interaction analysis. RESULTS: There was an educational
      gradient regarding the motivation to retire in the expected direction. The wish
      to retire before the age of 65 years was less common in male than in female older
      employees. Employees with a lower level of education and with a first generation
      migration background wished to retire early significantly less frequently than
      those without a migration background. Besides the interaction between migration
      background and education there were no further significant moderating effects of
      work-related or non-work-related variables on the association of social variables
      and the wish to retire early. CONCLUSION: According to the results there are
      differences between social groups of older employees in the motivation to retire
      early. The reasons and the final realization still have to be investigated. As a
      result, consequences for companies and politics with respect to the preservation
      of the work force can arise.

PMID- 30280241
TI  - Immunobiosis and probiosis: antimicrobial activity of lactic acid bacteria with a
      focus on their antiviral and antifungal properties.
AB  - Lactic acid bacteria (LAB), a heterogeneous group of bacteria that produce lactic
      acid as the main product of carbohydrate degradation, play an important role in
      the production and protection of fermented foods. Moreover, beside the
      technological use of these microorganisms added to control and steer food
      fermentations, their beneficial healthy properties are largely overt. Thus,
      numerous LAB strains have obtained the probiotic status, which entails the
      ability to maintain and promote a good health of consumers. In particular,
      increasing consideration is being focused on probiotic microorganisms that can
      improve the human immune response against dangerous viral and fungal enemies. For
      such beneficial microbes, the term "immunobiotics" has been coined. Together with
      an indirect host-mediated adverse effect against undesirable microorganisms, also
      a direct antagonistic activity of several LAB strains has been largely
      demonstrated. The purpose of this review is to provide a fullest possible
      overview of the antiviral and antifungal activities ascribed to probiotic LAB.
      The interest in this research field is substantiated by a large number of studies
      exploring the potential application of these beneficial microorganisms both as
      biopreservatives and immune-enhancers, aiming to reduce and/or eliminate the use
      of chemical agents to prevent the development of pathogenic, infectious, and/or
      degrading causes.

PMID- 30280242
TI  - Air-blood barrier thickening and alterations of alveolar epithelial type 2 cells
      in mouse lungs with disrupted hepcidin/ferroportin regulatory system.
AB  - Iron accumulates in the lungs of patients with common respiratory diseases or
      transfusion-dependent beta-thalassemia. Based on our previous work, we
      hypothesized that systemic iron overload affects the alveolar region of the lung
      and in particular the surfactant producing alveolar epithelial type II (AE2)
      cells. Mice with a point mutation in the iron exporter ferroportin, a model for
      human hemochromatosis type 4 were compared to wildtype mice (n = 5 each). Lungs
      were fixed and prepared for light and electron microscopy (EM) according to state
      of-the-art protocols to detect subcellular iron localization by scanning EM/EDX
      and to perform design-based stereology. Iron was detected as electron dense
      particles in membrane-bound organelles, likely lysosomes, in AE1 cells. AE2 cells
      were higher in number but had a lower mean volume in mutated mice. Lamellar body
      volume per AE2 cell was lower but total volume of lamellar bodies in the lung was
      comparable to wildtype mice. While the volume of alveoli was lower in mutated
      mice, the volume of alveolar ducts as well as the surface area, volume and the
      mean thickness and composition of the septa was similar in both genotypes. The
      thickness of the air-blood barrier was greater in the mutated than in the WT
      mice. In conclusion, disruption of systemic iron homeostasis affects the
      ultrastructure of interalveolar septa which is characterized by membrane-bound
      iron storage in AE1 cells, thickening of the air-blood barrier and hyperplasia
      and hypotrophy of AE2 cells despite normal total intracellular surfactant pools.
      The functional relevance of these findings requires further analysis to better
      understand the impact of iron on intra-alveolar surfactant function.

PMID- 30280243
TI  - How cancer cells attach to urinary bladder epithelium in vivo: study of the early
      stages of tumorigenesis in an orthotopic mouse bladder tumor model.
AB  - The majority of bladder cancers in humans are non-muscle-invasive cancers that
      recur frequently after standard treatment procedures. Mouse models are widely
      used to develop anti-tumor treatments. The purpose of our work was to establish
      an orthotopic mouse bladder tumor model and to explore early stages of
      implantation of cancerous MB49 cells in vivo using various labeling and
      microscopic techniques. To distinguish cancer cells from normal urothelial cells
      in mouse urinary bladders, we performed molecular characterization of MB49 cells
      before intravesical injection experiments. In this new approach we applied
      internalized metal nanoparticles to unequivocally discriminate cancer cells from
      normal cells. This method revealed that cancer cells attached to the urothelium
      or basal lamina within just 1 hour of intravesical injection, whereas small
      tumors and localized hyperplastic urothelial regions developed within two days.
      We found that cancer cells initially adhere to normal urothelial cells through
      filopodia and by focal contacts with basal lamina. This is the first in vivo
      characterization of intercellular contacts between cancerous and normal
      urothelial cells in the bladder. Our study yields new data about poorly known
      early events of tumorigenesis in vivo, which could be helpful for the translation
      into clinic.

PMID- 30280244
TI  - [Pacemaker and MRI in clinical practice].
AB  - The number of cardiac pacemaker wearers is continuously increasing in Germany as
      well as worldwide. The probability of indications for a magnetic resonance
      imaging (MRI) examination during the lifetime is approximately 50-75% for every
      person. An MRI examination is nowadays possible for pacemaker wearers under
      certain conditions. Due to the technical developments during the last 10 years
      certain MRI-conditional pacemakers are available. The recommendations of the
      German and American medical specialist societies currently allow an MRI
      examination in patients with conventional pacemakers beyond the approval
      conditions (off-label use) under prespecified conditions, based on the study
      data. This article summarizes the information on conditions of use and
      reprogramming strategies as well as on the study situation for the clinical
      routine.

PMID- 30280245
TI  - Comparison of radiomics machine-learning classifiers and feature selection for
      differentiation of sacral chordoma and sacral giant cell tumour based on 3D
      computed tomography features.
AB  - OBJECTIVE: We aimed to identify optimal machine-learning methods for preoperative
      differentiation of sacral chordoma (SC) and sacral giant cell tumour (SGCT) based
      on 3D non-enhanced computed tomography (CT) and CT-enhanced (CTE) features.
      METHODS: A total of 95 patients were divided into a training set and a validation
      set. Three best feature selection methods (Relief, least absolute shrinkage and
      selection operator (LASSO) and Random Forest (RF)) and three classification
      methods, including generalised linear models (GLM), support vector machines (SVM)
      and RF, were compared for their performance in distinguishing SC and SGCT. The
      performance of the radiomics model was investigated via area under the receiver
      operating characteristic curve (AUC) and accuracy (ACC) analysis. RESULTS: The
      selection method LASSO + classifier GLM had the highest AUC of 0.984 and ACC of
      0.897 in the validating set, followed by Relief + GLM (AUC = 0.909, ACC = 0.862)
      and LASSO + SVM (AUC = 0.900, ACC = 0.862) based on CTE features. For CT
      features, RF + GLM had the highest AUC of 0.889, while LASSO + GLM achieved a
      high ACC of 0.793 in the validating set. Regardless of the methods, CTE features
      significantly outperformed those from CT for the differentiation of SC and SGCT
      (ZAUC = -3.029, ZACC = -4.553; p < 0.05). CONCLUSIONS: Our study demonstrated CTE
      features performed better than CT features. The selection method LASSO +
      classifier GLM had the best performance in differentiation of SC and SGCT, which
      could enhance the application of radiomics methods in sacral tumours. KEY POINTS:
      * Sacral chordoma and sacral giant cell tumour are the two most common primary
      tumours of the sacrum with many common clinical and imaging characteristics. * A
      radiomics model helps clinicians to identify the histology of a sacral tumour. *
      CTE features should be preferred.

PMID- 30280246
TI  - Gastric cancer and imaging biomarkers: Part 1 - a critical review of DW-MRI and
      CE-MDCT findings.
AB  - : The current standard of care for gastric cancer imaging includes heterogeneity
      in image acquisition techniques and qualitative image interpretation. In addition
      to qualitative assessment, several imaging techniques, including diffusion
      weighted magnetic resonance imaging (DW-MRI), contrast-enhanced multidetector
      computed tomography (CE-MDCT), dynamic-contrast enhanced MRI and 18F
      fluorodeoxyglucose positron emission tomography, can allow quantitative analysis.
      However, so far there is no consensus regarding the application of functional
      imaging in the management of gastric cancer. The aim of this article is to
      specifically review two promising biomarkers for gastric cancer with reasonable
      spatial resolution: the apparent diffusion coefficient (ADC) from DW-MRI and
      textural features from CE-MDCT. We searched MEDLINE/ PubMed for manuscripts
      published from inception to 6 February 2018. Initially, we searched for (gastric
      cancer OR gastric tumour) AND diffusion weighted magnetic resonance imaging.
      Then, we searched for (gastric cancer OR gastric tumour) AND texture analysis AND
      computed tomography. We collated the results from the studies related to this
      query. There is evidence that: (1) the ADC is a promising biomarker for the
      evaluation of the aggressiveness (T and N stage), treatment response and
      prognosis of gastric cancer; (2) textural features are related to the degree of
      differentiation, Lauren classification, treatment response and prognosis of
      gastric cancer. We conclude that these imaging biomarkers hold promise as
      effective additional tools in the diagnostic pathway of gastric cancer and may
      facilitate the multidisciplinary work between the radiologist and clinician, and
      across different institutions, to provide a greater biological understanding of
      gastric cancer. KEY POINTS: * Quantitative imaging is the extraction of
      quantifiable features from medical images for the assessment of normal or
      pathological conditions and represents a promising area for gastric cancer. *
      Quantitative analysis from CE-MDCT and DW-MRI allows the extrapolation of
      multiple imaging biomarkers. * ADC from DW-MRI and CE- MDCT-based texture
      features are non-invasive, quantitative imaging biomarkers that hold promise in
      the evaluation of the aggressiveness, treatment response and prognosis of gastric
      cancer.

PMID- 30280247
TI  - Ultra-high-field arterial spin labelling MRI for non-contrast assessment of
      cortical lesion perfusion in multiple sclerosis.
AB  - OBJECTIVES: To assess the feasibility of using an optimised ultra-high-field high
      spatial-resolution low-distortion arterial spin labelling (ASL) MRI acquisition
      to measure focal haemodynamic pathology in cortical lesions (CLs) in multiple
      sclerosis (MS). METHODS: Twelve MS patients (eight female, mean age 50 years;
      range 35-64 years) gave informed consent and were scanned on a 7 Tesla Philips
      Achieva scanner. Perfusion data were collected at multiple post-labelling delay
      times using a single-slice flow-sensitive alternating inversion recovery ASL
      protocol with a balanced steady-state free precession readout scheme. CLs were
      identified using a high-resolution Phase-Sensitive Inversion Recovery (PSIR)
      scan. Significant differences in perfusion within CLs compared to immediately
      surrounding normal appearing grey matter (NAGMlocal) and total cortical normal
      appearing grey matter (NAGMcortical) were assessed using paired t-tests. RESULTS:
      Forty CLs were identified in PSIR scans that overlapped with the ASL acquisition
      coverage. After excluding lesions due to small size or intravascular
      contamination, 27 lesions were eligible for analysis. Mean perfusion was 40 +/-
      25 ml/100 g/min in CLs, 53 +/- 12 ml/100 g/min in NAGMlocal, and 53 +/- 8 ml/100
      g/min in NAGMcortical. CL perfusion was significantly reduced by 23 +/- 9% (mean
      +/- SE, p = 0.013) and 26 +/- 9% (p = 0.006) relative to NAGMlocal and
      NAGMcortical perfusion, respectively. CONCLUSION: This is the first ASL MRI study
      quantifying CL perfusion in MS at 7 Tesla, demonstrating that an optimised ASL
      acquisition is sensitive to focal haemodynamic pathology previously observed
      using dynamic susceptibility contrast MRI. ASL requires no exogenous contrast
      agent, making it a more appropriate tool to monitor longitudinal perfusion
      changes in MS, providing a new window to study lesion development. KEY POINTS: *
      Perfusion can be quantified within cortical lesions in multiple sclerosis using
      an optimised high spatial resolution arterial spin Labelling MRI acquisition at
      ultra-high-field. * The majority of cortical lesions assessed using arterial spin
      labelling are hypo-perfused compared to normal appearing grey matter, in
      agreement with dynamic susceptibility contrast MRI literature. * Arterial spin
      labelling MRI, which does not involve the injection of a contrast agent, is a
      safe and appropriate technique for repeat scanning of an individual patient.

PMID- 30280248
TI  - Pelvic MRI after induction chemotherapy and before long-course chemoradiation
      therapy for rectal cancer: What are the imaging findings?
AB  - OBJECTIVES: To determine the appearance of rectal cancer on MRI after oxaliplatin
      based chemotherapy (ICT) and make a preliminary assessment of MRI's value in
      predicting response to total neoadjuvant treatment (TNT). METHODS: In this IRB
      approved, HIPAA-compliant, retrospective study between 1 January 2010-20 October
      2014, pre- and post-ICT tumour T2 volume, relative T2 signal intensity (rT2SI),
      node size, signal intensity and border characteristics were assessed in 63
      patients (65 tumours) by three readers. The strength of association between the
      reference standard of histopathological percent tumour response and tumour volume
      change, rT2SI and lymph node characteristics was assessed with Spearman's
      correlation coefficient and Wilcoxon's rank sum test. Cox regression was used to
      assess association between DFS and radiological measures. RESULTS: Change in T2
      volume was not associated with TNT response. Change in rT2SI showed correlation
      with TNT response for one reader only using selective regions of interest (ROIs)
      and borderline correlation with response using total volume ROI. There was a
      significant negative correlation between baseline and post-ICT node size and TNT
      response (r = -0.25, p = 0.05; r = -0.35, p = 0.005, readers 1 and 2,
      respectively). Both baseline and post-induction median node sizes were
      significantly smaller in complete responders (p = 0.03, 0.001; readers 1 and 2,
      respectively). Change in largest baseline node size and decrease in post-ICT node
      signal heterogeneity were associated with 100% tumour response (p = 0.04). Nodal
      sizes at baseline and post-ICT MRI correlated with DFS. CONCLUSION: In patients
      undergoing post-ICT MRI, tumour volume did not correlate with TNT response, but
      decreased lymph node sizes were significantly associated with complete response
      to TNT as well as DFS. Relative T2SI showed borderline correlation with TNT
      response. KEY POINTS: * MRI-based tumour volume after induction chemotherapy and
      before chemoradiotherapy did not correlate with overall tumour response at the
      end of all treatment. * Lymph node size after induction chemotherapy and before
      chemoradiotherapy was strongly associated with complete pathological response
      after all treatment. * Lymph node sizes at baseline and post-induction
      chemotherapy MRI correlated with disease-free survival.

PMID- 30280249
TI  - Impact of image reconstruction methods on quantitative accuracy and variability
      of FDG-PET volumetric and textural measures in solid tumors.
AB  - OBJECTIVE: This study aims to assess the impact of different image reconstruction
      methods on PET/CT quantitative volumetric and textural parameters and the inter
      reconstruction variability of these measurements. METHODS: A total of 25 oncology
      patients with 65 lesions (between 2017 and 2018) and a phantom with signal-to
      background ratios (SBR) of 2 and 4 were included. All images were retrospectively
      reconstructed using OSEM, PSF only, TOF only, and TOFPSF with 3-, 5-, and 6.4-mm
      Gaussian filters. The metabolic tumor volume (MTV) and total lesion glycolysis
      (TLG) were measured. The relative percent error (DeltaMTV and DeltaTLG) with
      respect to true values, volume recovery coefficients, and Dice similarity
      coefficient, as well as inter-reconstruction variabilities were quantified and
      assessed. In clinical scans, textural features (coefficient of variation,
      skewness, and kurtosis) were determined. RESULTS: Among reconstruction methods,
      mean DeltaMTV differed by -163.5 +/- 14.1% to 6.3 +/- 6.2% at SBR2 and -42.7 +/-
      36.7% to 8.6 +/- 3.1 at SBR4. Dice similarity coefficient significantly increased
      by increasing SBR from 2 to 4, ranging from 25.7 to 83.4% between reconstruction
      methods. Mean DeltaTLG was -12.0 +/- 1.7 for diameters > 17 mm and -17.8 +/- 7.8
      for diameters <= 17 mm at SBR4. It was -31.7 +/- 4.3 for diameters > 17 mm and 
      14.2 +/- 5.8 for diameters <= 17 mm at SBR2. Textural features were prone to
      variations by reconstruction methods (p < 0.05). CONCLUSIONS: Inter
      reconstruction variability was significantly affected by the target size, SBR,
      and cut-off threshold value. In small tumors, inter-reconstruction variability
      was noteworthy, and quantitative parameters were strongly affected. TOFPSF
      reconstruction with small filter size produced greater improvements in
      performance and accuracy in quantitative PET/CT imaging. KEY POINTS: *
      Quantitative volumetric PET evaluation is critical for the analysis of tumors. *
      However, volumetric and textural evaluation is prone to important variations
      according to different image reconstruction settings. * TOFPSF reconstruction
      with small filter size improves quantitative analysis.

PMID- 30280250
TI  - Meniscal body extrusion and cartilage coverage in middle-aged and elderly without
      radiographic knee osteoarthritis.
AB  - OBJECTIVES: To determine meniscal extrusion and cartilage coverage on magnetic
      resonance (MR) images and factors associated with these parameters in knees of
      middle-aged and elderly persons free from radiographic tibiofemoral
      osteoarthritis (OA). METHODS: Seven hundred eighteen persons, free of
      radiographic tibiofemoral OA, aged 50-90 years from Framingham, MA, USA, were
      included. We measured meniscal extrusion on 1.5 T MRI of both knees to evaluate
      both medial and lateral meniscal body extrusion and cartilage coverage. We also
      determined meniscal morphology and structural integrity. The multivariable
      association with age, body mass index (BMI), and ipsilateral meniscal damage was
      also evaluated. RESULTS: The mean meniscal body extrusion medially was 2.7 mm and
      laterally 1.8 mm. The tibial cartilage coverage was about 30% of ipsilateral
      cartilage surface (both compartments). The presence of ipsilateral meniscal
      damage was associated with more extrusion in only the medial compartment, 1.0 mm
      in men and 0.6 mm in women, and less cartilage coverage proportion, -5.5% in men
      and -4.6% in women. CONCLUSIONS: Mean medial meniscal body extrusion in middle
      aged or older persons without radiographic tibiofemoral OA approximates the
      commonly used cutoff (3 mm) to denote pathological extrusion. Medial meniscal
      damage is a factor associated with medial meniscal body extrusion and less
      cartilage coverage. KEY POINTS: * Medial meniscal extrusion in middle-aged/older
      persons without OA is around 3 mm. * Lateral meniscal extrusion in middle
      aged/older persons without OA is around 2 mm. * Meniscal damage is associated
      with medial meniscal extrusion and less cartilage coverage.

PMID- 30280251
TI  - Did cis- and trans-defensins derive from a common ancestor?
AB  - Defensins are small, cysteine-rich, cationic antimicrobial peptides, serving as
      effectors of the innate immune system and modulators of the adaptive immune
      system. They extensively exist in multicellular organisms and are divided into
      cis and trans according to their disulfide bridge connectivity patterns. It has
      been proposed that these two types of defensins convergently originated from
      different ancestors. Here, we report the discovery of a structural signature
      involved in the formation of the cysteine-stabilized alpha-helix/beta-sheet
      (CSalphabeta) fold of the cis-defensins in some trans-beta-defensins, with only
      one amino acid indel (CXC vs. CC. C, cysteine; X, any amino acid). The indel of
      the X residue in the structural signature provides a possible explanation as to
      why cis- and trans-defensins possess different folds and connectivity patterns of
      disulfide bridges formed in evolution. Although our attempt to convert the
      structure type of a present-day trans-defensin with the X residue deleted was
      unsuccessful due to the low solubility of the synthetic peptide, a combination of
      data from structural signature, function, and phylogenetic distribution suggests
      that these defensins may have descended from a common ancestor. In this
      evolutionary scenario, we propose that a progenitor cis-scaffold might gradually
      evolve into a trans-defensin after deleting the X residue in specific lineages.
      This proposal adds a new dimension to more deeply studying the evolutionary
      relationship of defensins with different folds and of other distantly related
      proteins.

PMID- 30280252
TI  - Trends and outcomes of sphincter-preserving surgery for rectal cancer: a national
      cancer database study.
AB  - PURPOSE: Previous studies have shown that sphincter-preserving surgery is
      associated with better quality of life in postsurgical rectal cancer patients.
      However, the factors predicting the likelihood of undergoing sphincter-preserving
      surgery have not been well-described. The aim of this study was to report the
      factors that determined the likelihood of undergoing sphincter-preserving
      surgery. METHODS: Characteristics of 24,018 rectal cancer patients undergoing
      sphincter-preserving surgery and abdominoperineal resection diagnosed from 2008
      to 2012 from the National Cancer Database were investigated retrospectively for
      rate, pattern, and differences in mortality. Cox proportional hazards models were
      used to calculate hazard ratios for assessing mortality. Odds ratios were
      calculated using logistic regressions models for outcome sphincter-preserving
      surgery. RESULTS: Eighteen thousand four hundred fifty-two (77%) patients had
      sphincter-preserving surgery. Majority of sphincter-preserving surgery patients
      were aged < 70 (74%), had private insurance (52%), and got treatment at a
      comprehensive community cancer program (54%). Multivariable analysis showed that
      patients with age >= 70 (OR 0.87, 95% CI 0.80-0.95), male gender (OR 0.90, 95% CI
      0.84-0.96), having Medicare (OR 0.83, 95% CI 0.76-0.90), Medicaid (OR 0.72, 95%
      CI 0.63-0.81), and poorly differentiated grade (OR 0.78, 95% CI 0.71-0.85) were
      less likely to undergo sphincter-preserving surgery. Multivariable analysis
      showed that patients having abdominoperineal resection have higher likelihood of
      mortality than sphincter-preserving surgery (HR 1.26, 95% CI 1.16-1.36).
      CONCLUSIONS: We were able to identify several patient and tumor-related factors
      impacting the likelihood of undergoing sphincter-preserving surgery. Patients
      undergoing non-sphincter sparing surgery had a higher mortality that sphincter
      preservation.

PMID- 30280253
TI  - Starry-sky bowels.
AB  - PURPOSE: Because of the increasing usage of lanthanum carbonate in dialysis
      patients, clinicians should be aware of its typical radiographic appearance.
      METHODS: A dialysis patient received a plain film and a computed tomography, both
      showing a "starry-sky" appearance in the nearly whole colon, and the radiological
      report mistakenly denoted it as barium. RESULTS: The patient denied any exposure
      to barium or radiocontrast medium. Tracing back her medication history, lanthanum
      carbonate, 500 mg twice a day, has been prescribed for her hyperphosphatemia in
      recent 5 months. CONCLUSIONS: Clinicians should be aware of typical radiographic
      appearance of lanthanum carbonate to avoid unnecessary management and may also
      take its radiopaque characteristic as an advantage to assess the patient's drug
      adherence.

PMID- 30280254
TI  - Feature Extraction Using Dominant Local Texture-Color Patterns (DLTCP) and
      Classification of Color Images.
AB  - Feature extraction and classification are considered to be the major tasks in
      image processing applications. This paper proposes a novel method to extract the
      features of a color image for classification. The proposed method, Dominant Local
      Texture-Color Patterns (DLTCP) is based on the Dominant Texture and Dominant
      Color channels in a RGB color space. The dominant texture pattern represents a
      channel among RGB with maximum variations in the texture and the dominant color
      pattern represents the color channel with the maximum pixel intensity. The
      combination of channels with dominant texture pattern and dominant color pattern
      is assigned a unique value which is used to extract the features of an image. The
      proposed texture-color features is tested for rotational, illumination and scale
      invariance property using the color images taken from Outex and Vistex databases.
      It is experimentally shown that the proposed method achieves the highest accuracy
      in classification using K-Nearest Neighbor (KNN) classifier under various
      challenges.

PMID- 30280255
TI  - Correction to: Ultrastructure and secretion of glandular trichomes in species of
      subtribe Cajaninae Benth (Leguminosae, Phaseoleae).
AB  - In the original version of this article unfortunately some symbols did not appear
      in the plates caused by technical problems of the journal. We apologize for any
      inconvenience caused.

PMID- 30280256
TI  - A comparison of the effects of selected mono-ethnic urban environments on the
      autonomic functions of Muslim and Jewish women in Israel.
AB  - Few previous studies evaluated ethnic differences in the effects of urban
      environments on the autonomic balance in intra-ethnic environments and the
      mediation effects of environmental exposures (air pollution, noise, and thermal
      load). In a field experimental study, we exposed 48 Muslim and 24 Jewish women to
      park, town center, and residential street in Israeli mono-ethnic small towns.
      Heart rate variability (HRV), noise, thermal load, and carbon monoxide (CO) were
      measured by portable devices while visiting the environments and were analyzed
      using mixed models. The results highlight the restorative effect of parks on both
      ethnic groups with stronger effect for Jewish women compared to Muslim women
      (beta coefficient (95% confidence interval (CI)): - 6.45(- 6.70, - 6.20); - 4.99
      (- 5.15, - 4.83), respectively). However, significant differences were recorded
      in Muslim and Jewish coping with the environments and the environmental exposures
      as measured by HRV.

PMID- 30280257
TI  - The difference of stress distribution of maxillary expansion using rapid
      maxillary expander (RME) and maxillary skeletal expander (MSE)-a finite element
      analysis.
AB  - BACKGROUND: Maxillary skeletal expander (MSE) in combination with miniscrews was
      developed to overcome the drawbacks that may have resulted from the application
      of conventional rapid maxillary expander (RME). This research was conducted to
      analyze the difference of stress distribution of maxillary expansion using RME
      and MSE in the region of interests (ROIs): first molars (M1), palatal alveolar
      bones of M1, palatine sutures, zygomatic sutures, miniscrews, and their
      surrounding bones. METHODS: A dry skull was scanned using CBCT and rendered into
      a three-dimensional (3D) model of craniomaxillary structures. The data analysis
      was done both visually and numerically. RESULT: The stress distributions in RME
      group were located at the palatal side of M1, mesial side of palatal alveolar of
      M1, pulp chamber of M1, and inferior cortex of palatine sutures. The stress
      distributions in the MSE group were located at the distopalatal cusp of M1,
      palatal side of palatal alveolar of M1, and inferior and superior cortex of
      palatine sutures. The stress distributions in zygomatic sutures on both groups
      were located at the zygomaticotemporal sutures, whereas in the miniscrews, the
      stress were located at the anterior miniscrews and palatal side of surrounding
      bones. CONCLUSIONS: There were significant differences of stress distribution of
      maxillary expansion measured in the ROIs in the craniomaxillary 3D model using
      RME and MSE.

PMID- 30280259
TI  - Post-traumatic hydrocephalus following decompressive craniectomy: how well can it
      be predicted?

PMID- 30280260
TI  - Earlier detection of Alzheimer disease using N-fold cross validation approach.
AB  - According to the recent study, world-wide 40 million patients are affected by
      Alzheimer disease (AD) because it is one of the dangerous neurodegenerative
      disorders. This AD disease has less symptoms such as short term memory loss, mood
      swings, problem with language understanding and behavioral issues. Due to these
      low symptoms, AD disease is difficult to recognize in the early stage. So, the
      automated computer aided system need to be developed for recognizing the AD
      disease for minimizing the mortality rate. Initially, brain MRI image is
      collected from patients which are processed by applying different processing
      steps such as noise removal, segmentation, feature extraction, feature selection
      and classification. The captured MRI image has noise that is eliminated by
      applying the Lucy-Richardson approach which examines the each pixel in the image
      and removes the Gaussian noise which also eliminates the blur image. After
      eliminating the noise pixel from the image, affected region is segmented by
      Prolong adaptive exclusive analytical Atlas approach. From the segmented region,
      different GLCM statistical features are extracted and optimal features subset is
      selected by applying the hybrid wrapper filtering approach. This selected
      features are analyzed by N-fold cross validation approach which recognizes the AD
      related features successfully. Then the efficiency of the system is evaluated
      with the help of MATLAB based experimental results, in which Alzheimer's Disease
      Neuroimaging Initiative (ADNI) dataset images are utilized for examining the
      efficiency in terms of sensitivity, specificity, ROC curve and accuracy.

PMID- 30280258
TI  - Colorimetric adenosine aptasensor based on DNA cycling amplification and salt
      induced aggregation of gold nanoparticles.
AB  - An aptamer based assay is described for the colorimetric detection of adenosine.
      The presence of adenosine triggers the deformation of hairpin DNA oligonucleotide
      (HP1) containing adenosine aptamer and then hybridizes another unlabeled hairpin
      DNA oligonucleotide (HP2). This leads to the formation of a double strand with a
      blunt 3' terminal. After exonuclease III (Exo III)-assisted degradation, the
      guanine-rich strand (GRS) is released from HP2. Hence, the adenosine-HP1 complex
      is released to the solution where it can hybridize another HP2 and initiate many
      cycles of the digestion reaction with the assistance of Exo III. This leads to
      the generation of a large number of GRS strands after multiple cycles. The GRS
      stabilize the red AuNPs against aggregation in the presence of potassium ions.
      If, however, GRS forms a G-quadruplex, it loses its ability to protect gold
      nanoparticles (AuNPs) from salt-induced AuNP aggregation. Therefore, the color of
      the solution changes from red to blue which can be visually observed. This
      colorimetric assay has a 0.13 nM detection limit and a wide linear range that
      extends from 5 nM to 1 MUM. Graphical abstract Schematic presentation of a
      colorimetric aptamer biosensor for adenosine detection based on DNA cycling
      amplification and salt-induced aggregation of gold nanoparticles.

PMID- 30280262
TI  - Population Pharmacokinetics and Exposure-Response Relationships of Naldemedine.
AB  - PURPOSE: To characterize population pharmacokinetic (PK) of naldemedine, to
      identify factors which influence naldemedine PK, and to evaluate their clinical
      relevancy based on exposure-response relationships. METHODS: A population PK
      model was developed with pooled naldemedine concentrations from healthy subjects,
      patients with chronic non-cancer pain and opioid-induced constipation (OIC), and
      cancer patients with OIC. Exposure-response analyses were performed with efficacy
      (responder or non-responder) and safety (occurrence of gastrointestinal disorders
      or not) data in phase 2b and phase 3 studies. RESULTS: Naldemedine plasma
      concentrations were adequately described by a 2-compartment model with first
      order absorption and absorption lag time. The final model included the effects of
      age, creatinine clearance, race, and gender on apparent total clearance; the
      effects of body weight, health status, and food condition on apparent volume of
      central compartment; and the effect of age on first-order rate of absorption.
      When subjects took 0.2 mg of naldemedine once daily, the probability of
      spontaneous bowel movement (SBM) responders was predicted to be approximately
      50%, while that of severe gastrointestinal disorders was predicted to be less
      than 3%. The influence of the covariates on PK was not considered clinically
      significant because similar efficacy and safety were expected based on the
      exposure-response analysis. CONCLUSIONS: The covariates are identified in the
      population PK analysis; however, no dose-adjustment is required for them based on
      the exposure-response analysis.

PMID- 30280261
TI  - Septic Encephalopathy.
AB  - PURPOSE OF THE REVIEW: To discuss the diagnostic approach to patients with septic
      encephalopathy as well as the need for specific neuro-monitoring and the
      perspectives on future therapeutic approaches in this setting. RECENT FINDINGS:
      Most of data-concern experimental studies evaluating the pathophysiology of
      septic encephalopathy. A combination of neurodegenerative pathways with
      neurovascular injury is the cornerstone for the development of such complication
      and the long-term neurological sequelae among survivors. Septic encephalopathy is
      a common complication in septic patients. Clinical presentation may range from
      mild confusion and disorientation to convulsions and deep coma. The diagnosis of
      septic encephalopathy is made difficult by the lack of any specific clinical and
      non-clinical feature, in particular among sedated patients in whom neurological
      examination is unreliable. In spite of the high mortality rate associated with
      this condition, there is no prophylactic or targeted therapy to reduce or
      minimize brain damage in septic patients and clinical management is limited to
      the treatment of the underlying infection.

PMID- 30280264
TI  - Adaptive Real-Time Removal of Impulse Noise in Medical Images.
AB  - Noise is an important factor that degrades the quality of medical images. Impulse
      noise is a common noise caused by malfunctioning of sensor elements or errors in
      the transmission of images. In medical images due to presence of white foreground
      and black background, many pixels have intensities similar to impulse noise and
      hence the distinction between noisy and regular pixels is difficult. Therefore,
      it is important to design a method to accurately remove this type of noise. In
      addition to the accuracy, the complexity of the method is very important in terms
      of hardware implementation. In this paper a low complexity de-noising method is
      proposed that distinguishes between noisy and non-noisy pixels and removes the
      noise by local analysis of the image blocks. All steps are designed to have low
      hardware complexity. Simulation results show that in the case of magnetic
      resonance images, the proposed method removes impulse noise with an acceptable
      accuracy.

PMID- 30280263
TI  - Privacy-Preserving and Efficient Truly Three-Factor Authentication Scheme for
      Telecare Medical Information Systems.
AB  - Significant development of information technologies has made Telecare Medical
      Information Systems (TMISs) increasingly popular. In a TMIS, patients upload
      their medical data through smart devices to obtain a doctor's diagnosis. However,
      these smart devices have limited computing and storage capacities, so it is
      difficult to store substantial patient information and to support time-consuming
      operations. Moreover, although many three-factor authentication protocols have
      been proposed for TMISs, the problems of privacy leaks and other security flaws
      are serious. In addition, authentication factors are verified at the user side in
      most protocols, giving users a high level of trust and resulting in a potential
      lack of security. In this paper, we propose a novel efficient truly three-factor
      authentication protocol for TMISs. In our proposed protocol, three factors (i.e.,
      password, smart card and biometrics) are verified at the server side, which
      reduces the storage and computational burden of the user side. Additionally, our
      proposed protocol uses only lightweight operators and is thus efficient. A formal
      proof analysis demonstrates that our proposed protocol is provably secure in the
      random oracle model. The performance evaluation shows that the proposed protocol
      is very efficient and suitable for TMISs.

PMID- 30280265
TI  - The easy-to-hard training advantage with real-world medical images.
AB  - Many medical professions require practitioners to perform visual categorizations
      in domains such as radiology, dermatology, and neurology. However, acquiring
      visual expertise is tedious and time-consuming and the perceptual strategies
      mediating visual categorization skills are poorly understood. In this paper, the
      Ease algorithm was developed to predict an item's categorization difficulty (Ease
      value) based on the item's perceptual similarity to all within-category items
      versus between-category items in the dataset. In this study, Ease values were
      used to construct an easy-to-hard and hard-to-easy training schedule for teaching
      melanoma diagnosis. Whereas previous visual training studies suggest that an easy
      to-hard schedule benefits learning outcomes, no studies to date have demonstrated
      the easy-to-hard advantage with complex, real-world images. In our study, 237
      melanoma and benign images were collected for training and testing purposes. The
      diagnostic accuracy of images was verified by an expert dermatologist. Based on
      their Ease values, the items were grouped into easy, medium, and hard categories,
      each containing an equal number of melanoma and benign lesions. During training,
      participants categorized images of skin lesions as either benign or melanoma and
      were given corrective feedback after each trial. In the easy-to-hard training
      condition, participants learned to categorize all the easy items first, followed
      by the medium items, and finally the hard items. Participants in the hard-to-easy
      training condition learned items in the reverse order. Post-training results
      showed that training in both conditions transferred to the classification of new
      melanoma and benign images. Participants in the easy-to-hard condition showed
      modest advantages both in the acquisition and retention of the melanoma diagnosis
      skills, but neither scheduling condition exhibited a gross advantage. The Ease
      values of the items predicted categorization accuracy after, but not before
      training, suggesting that the Ease algorithm is a promising tool for optimizing
      medical training in visual categorization.

PMID- 30280266
TI  - Theoretical design of novel energetic salts derived from bicyclo-HMX.
AB  - We designed three novel cage energetic anions by introducing ionic bridges
      containing NTheta, N(OTheta) and N(NThetaNO2) into cis-2,4,6,8-tetranitro-1H,5H
      2,4,6,8- tetraazabicyclo[3.3.0] octane (bicyclo-HMX or BCMHX). The properties of
      21 energetic salts, based on cage anions and ammonium-based cations, were studied
      by density functional theory (DFT) and volume-based thermodynamics (VBT)
      calculations. Compared to the parent nonionic BCHMX, most title salts have lower
      predicted impact sensitivities, higher predicted densities, larger predicted
      heats of formation (HOFs) and better predicted detonation properties. In
      particular, 11 energetic salts not only exhibit excellent predicted energetic
      properties, superior to 2,4,6,8,10,12-hexanitrohexaazaisowurtzitane (CL-20), but
      also have lower predicted sensitivity than CL-20. The best salt had a predicted
      detonation velocity of 10.06 km s-1, a predicted detonation pressure of 48.54 GPa
      and a predicted sensitivity (h50) of 23.99 cm. By introducing ionic bridges into
      highly nitrated rings, or modifying the original bridge with ionic bridges, some
      highly nitrated cage compounds with both excellent performance and low
      sensitivity can be developed strategically. Graphical abstract Heats of
      detonation, detonation velocities, and detonation pressures of salts derived from
      bicyclo-HMX.

PMID- 30280268
TI  - Lanthanide doped carbon dots as a fluorescence chromaticity-based pH probe.
AB  - A colorimetric and fluorescent pH probe was designed by doping carbon dots (C
      dots) with Eu(III), Tb(III) and 2,6-pyridinedicarboxylic acid (DPA). The
      resulting nanoparticles were applied as fluorescent indicators for pH values
      (best detected at excitation/emission wavelengths of 272/545, 614 nm). The pH
      induced optical effects are due to pH induced variations in energy transfer. The
      fluorescence of the probe shows a continuous color variation, and a linear change
      with pH values in the range from 3.0 to 10.0 can be established by using a
      Commission Internationale de L'Eclairage (CIE) chromaticity diagram. This new
      kind of pH nanoprobe is more accurate than previously reported pH indicator
      probes because the pH value can be calculated by using chromaticity coordinates
      that only depend on the chromaticity. The pH nanoprobe was applied to visualize
      pH values in human breast adenocarcinoma cells (MCF-7). Graphical abstract Carbon
      dots modified with Eu(III) and Tb(III) complexes of 2,6-pyridinedicarboxylic acid
      (DPA) were prepared. The doped carbon dots were used as a pH-sensitive
      nanosensor. The fluorescence chromaticity of the nanoparticles changes with the
      variation of pH value.

PMID- 30280267
TI  - Longitudinal Progression Markers of Parkinson's Disease: Current View on
      Structural Imaging.
AB  - PURPOSE OF REVIEW: Advances in neuroimaging techniques pave a rich avenue for in
      vivo progression biomarkers, which can objectively and noninvasively assess the
      long-term dynamic alterations in the brain of Parkinson's disease (PD) patients.
      This article reviews recent progress in structural magnetic resonance imaging
      (MRI) tools to track disease progression in PD, and discusses specific criteria a
      neuroimaging tool needs to meet to be a progression biomarker of PD and the
      potential applications of these techniques in PD based on current evidence.
      RECENT FINDINGS: Recent longitudinal studies showed that quantitative structural
      MRI markers derived from T1-weighted, diffusion-weighted, neuromelanin-sensitive,
      and iron-sensitive imaging have the potential to track disease progression in PD.
      However, validation of these progression biomarkers is only beginning, and more
      work is required for multisite validation, the sample size for use in a clinical
      trial, and drug-responsiveness of most of these biomarkers. At present, the most
      clinical trial-ready biomarker is free-water diffusion imaging of the substantia
      nigra and seems well established to be used in disease-modifying studies in PD. A
      variety of structural imaging biomarkers are promising candidates to be
      progression biomarkers in PD. Further studies are needed to elucidate the
      sensitivity, reliability, sample size, and effect of confounding factors of these
      progression biomarkers.

PMID- 30280269
TI  - Compression of CT Images using Contextual Vector Quantization with Simulated
      Annealing for Telemedicine Application.
AB  - The role of compression is vital in telemedicine for the storage and transmission
      of medical images. This work is based on Contextual Vector Quantization (CVQ)
      compression algorithm with codebook optimization by Simulated Annealing (SA) for
      the compression of CT images. The region of interest (foreground) and background
      are separated initially by region growing algorithm. The region of interest is
      encoded with low compression ratio and high bit rate; the background region is
      encoded with high compression ratio and low bit rate. The codebook generated from
      foreground and background is merged, optimized by simulated annealing algorithm.
      The performance of CVQ-SA algorithm was validated in terms of metrics like Peak
      to Signal Noise Ratio (PSNR), Mean Square Error (MSE) and Compression Ratio (CR),
      the result was superior when compared with classical VQ, CVQ, JPEG lossless and
      JPEG lossy algorithms. The algorithms are developed in Matlab 2010a and tested on
      real-time abdomen CT datasets. The quality of reconstructed image was also
      validated by metrics like Structural Content (SC), Normalized Absolute Error
      (NAE), Normalized Cross Correlation (NCC) and statistical analysis was performed
      by Mann Whitney U Test. The outcome of this work will be an aid in the field of
      telemedicine for the transfer of medical images.

PMID- 30280270
TI  - Epigenetics Variation and Pathogenesis in Diabetes.
AB  - PURPOSE OF REVIEW: Great strides have recently been made in elucidating the role
      of genetic sequence variation in diabetes pathogenesis. Increasingly, studies are
      focusing on other factors that may contribute to the pathogenesis of diabetes,
      such as epigenetics, a term "traditionally" encompassing changes to the DNA that
      do not alter sequence and are heritable (primary methylation and histone
      modification) but often expanded to include microRNAs. This review summarizes
      latest findings on the role of epigenetics in diabetes pathogenesis. RECENT
      FINDINGS: Recent studies illustrate roles for methylation changes, histone
      modification, imprinting, and microRNAs across several diabetes types and
      complications. Notably, methylation changes in the human leukocyte antigen (HLA)
      region have been found to precede the development of type 1 diabetes. In type 2
      diabetes, lifestyle factors appear to interact with epigenetic mechanisms in
      pathogenesis. Emerging technologies have allowed increasingly comprehensive
      descriptive analysis of the role of epigenetic mechanisms in diabetes
      pathogenesis which have yielded meaningful insights into effects on expression of
      relevant genes. These findings have the potential to inform future development of
      predictive testing to enable primary prevention and further work to uncover the
      complex pathogenesis of diabetes.

PMID- 30280271
TI  - A Novel Enhanced Gray Scale Adaptive Method for Prediction of Breast Cancer.
AB  - Breast cancer is the important problem across the globe in which, most of the
      women are suffering without knowing the causes and effects of the cancer cells.
      Mammographic is the most powerful tool for the diagnosis of the Breast cancer.
      The analysis of this mammogram images proves to be more vital in terms of
      diagnosis but the accuracy level still needs improvisation. Several intelligent
      techniques are suggested for the detection of Microcalcification, Clusters,
      Masses, Spiculate lesions, Asymmetry and Architectural distortions in the
      mammograms. But the prediction of the cancer levels needs more research light.
      For the determination of the higher level of accuracy and prediction, the
      proposed algorithm called Enhanced Gray Scale Adaptive Method (EGAM) which works
      on the principle of combination of K-GLCM and Extreme Fuzzy Learning Machines
      (EFLM). The proposed algorithm has achieved 99% accuracy and less computation
      time in terms of classification, detection and prediction when compared with the
      existing intelligent algorithms.

PMID- 30280272
TI  - Origin and distribution of nitrate in water well of settlement areas in
      Yogyakarta, Indonesia.
AB  - Pollution of nitrate in water wells in Yogyakarta City was reported to increase
      for two decades. This study aimed to describe nitrate contamination in the water
      wells of colorectal cancer (CRC) and inflammatory bowel disease (IBD) patients,
      previously described elsewhere. Nitrate and chloride content of 150 water samples
      from the wells of patients with CRC and IBD who were residing in Yogyakarta,
      Sleman, or Bantul districts were examined. Description of nitrate contamination
      was presented in the form of box plot charts and map. Kruskal-Wallis analysis was
      used to measure the difference of nitrate concentration in three areas of study.
      Comparisons of nitrate and chloride concentrations were used to determine the
      source of nitrate contamination in water well. Fisher's exact test was used to
      describe the relationship of well distance with the septic tank to nitrate
      concentration in water well. The wells in Yogyakarta City had the highest median
      nitrate content compared to Sleman and Bantul (P = 0.001) with the median of
      56.6, 13.1, and 7.7 for Yogyakarta, Sleman, and Bantul, respectively, and most
      tested samples exceed WHO safe drinking water standards. The spread of nitrate
      contamination has occurred in areas adjacent to Yogyakarta City compared to the
      previous report. The ratio of nitrate to chloride (1-8:1) suggested that the
      source of nitrate contamination in water wells in the study area came from feces
      due to inadequate on-site sanitation. The mapping showed nitrate contamination in
      water wells in Yogyakarta City, Sleman, and Bantul districts had spread according
      to urban development.

PMID- 30280274
TI  - Ketosis-Prone Diabetes (Flatbush Diabetes): an Emerging Worldwide Clinically
      Important Entity.
AB  - PURPOSE OF REVIEW: Ketosis-prone diabetes or Flatbush diabetes has been widely
      recognized as a clinical entity since 1984. Most of the early clinical studies
      focused on African American or Afro-Caribbean individuals. It is now being
      recognized as an important clinical entity in sub-Saharan Africans, Asian and
      Indian populations, and Hispanic populations. Major questions remain as to its
      pathogenesis and whether it is a unique type of diabetes or a subset of more
      severe type 2 diabetes with greater loss of insulin action in target tissues.
      This review summarizes the main clinical and mechanistic studies to improve the
      understanding of ketosis-prone (Flatbush) diabetes. RECENT FINDINGS: Little data
      are available on the magnitude of KPD in the different susceptible populations.
      It is relatively common in black populations. KPD is defined as a syndrome in
      which diabetes commences with ketoacidosis in individuals who are GAD and anti
      islet cell antibody negative and have no known precipitating causes. The patients
      present during middle age, are overweight or mildly obese, and in many reports
      are more likely to be male. After intensive initial insulin therapy, many
      patients become insulin independent and can be well controlled on diet alone or
      diet plus oral medications. The clinical course of KPD is like that of patients
      with type 2 diabetes rather than that of type 1 diabetes. Little differences are
      found in the clinical characteristics and clinical outcomes between patients
      presenting with KPD and those presenting with severe hyperglycemia with no
      ketoacidosis. The mechanisms responsible for the development of ketosis-prone
      diabetes as well its remission remain unknown.

PMID- 30280273
TI  - A Cell Assay for Detecting Anti-PEG Immune Response against PEG-Modified
      Therapeutics.
AB  - PURPOSE: Immunogenicity of PEGylated proteins and nanomedicines represents a
      potential impediment against their development and use in clinical settings. The
      purpose of this study is to develop a method for detecting anti-PEG immunity of
      PEGylated proteins and/or nanomedicines using flow cytometry. METHODS: The
      binding of fluorescence-labeled mPEG-modified liposomes to HIK-G11 cells, PEG
      specific hybridoma cells, or spleen cells was evaluated by flow cytometry for
      detecting immunogenicity of PEGylated therapeutics. RESULTS: The fluorescence
      labeled methoxy PEG (mPEG)-modified liposomes were efficiently bound to HIK-G11
      cells. Such staining with fluorescence-labeled mPEG-modified liposomes was
      significantly inhibited in the presence of either non-labeled mPEG-modified
      liposomes or mPEG-modified ovalbumin (OVA) but not polyglycerol-modified
      liposomes. In addition, we found that mPEG-modified liposomes, highly
      immunogenic, caused proliferation of PEG-specific cells, while hydroxyl PEG
      modified liposomes, less immunogenic, scarcely caused. Furthermore, after
      intravenous injection of mPEG-modified liposomes, the percentage of PEG-specific
      cells in the splenocytes, as determined by flow cytometry, corresponded well with
      the production level of anti-PEG antibodies, as determined by ELISA. CONCLUSIONS:
      PEG-specific B cell assay we introduced may become a useful method to detect an
      anti-PEG immune response against PEGylated therapeutics and clarify the mechanism
      for anti-PEG immune responses.

PMID- 30280275
TI  - Combination Metabolomics Approach for Identifying Endogenous Substrates of
      Carnitine/Organic Cation Transporter OCTN1.
AB  - PURPOSE: Solute carrier SLC22A4 encodes the carnitine/organic cation transporter
      OCTN1 and is associated with inflammatory bowel disease, although little is known
      about how this gene is linked to pathogenesis. The aim of the present study was
      to identify endogenous substrates that are associated with gastrointestinal
      inflammation. METHODS: HEK293/OCTN1 and mock cells were incubated with colon
      extracts isolated from dextran sodium sulfate-induced colitis mice; the
      subsequent cell lysates were mixed with the amino group selective reagent 3
      aminopyridyl-N-hydroxysuccinimidyl carbamate (APDS), to selectively label OCTN1
      substrates. Precursor ion scanning against the fragment ion of APDS was then used
      to identify candidate OCTN1 substrates. RESULTS: Over 10,000 peaks were detected
      by precursor ion scanning; m/z 342 had a higher signal in HEK293/OCTN1 compared
      to mock cells. This peak was detected as a divalent ion that contained four APDS
      derived fragments and was identified as spermine. Spermine concentration in
      peripheral blood mononuclear cells from octn1 gene knockout mice (octn1-/-) was
      significantly lower than in wild-type mice. Lipopolysaccharide-induced gene
      expression of inflammatory cytokines in peritoneal macrophages from octn1-/- mice
      was lower than in wild-type mice. CONCLUSIONS: The combination metabolomics
      approach can provide a novel tool to identify endogenous substrates of OCTN1.

PMID- 30280276
TI  - Microplastics in municipal wastewater treatment plants in Turkey: a comparison of
      the influent and secondary effluent concentrations.
AB  - Wastewater treatment plants are one of the primary pathways through which
      microplastics enter aquatic environments. In this study, we have determined the
      microplastic concentrations of the influent and secondary effluent water of two
      wastewater treatment plants in Turkey. For this purpose, we have taken samples of
      the influent and effluent water of Seyhan and Yuregir wastewater treatment
      facilities for 6 days in August 2017 and determined their microplastics' content
      both visually and using MU-Raman spectroscopy. The results showed that the
      influent of the wastewater treatment contained 1 million-6.5 million particles
      per day, while the effluent contained 220,000-1.5 million particles per day. The
      removal rate of microplastics was found to be between 73 and 79%. In total, seven
      different types of polymers were detected. The most frequently observed polymer
      type was polyester.

PMID- 30280277
TI  - Quality Comparison of Biosimilar and Copy Filgrastim Products with the Innovator
      Product.
AB  - PURPOSE: Filgrastim, a recombinant human granulocyte-colony stimulating factor,
      is widely used to treat congenital and acquired neutropenia. Following patent
      expiration of the innovator filgrastim product, biosimilar filgrastim products
      have been approved in the EU and shown to be comparable with the innovator with
      respect to quality, safety and efficacy. In less regulated markets, copy
      filgrastim products are available but data about their quality are scarce. In the
      present study, we provide a head-to-head comparative study on the quality of
      biosimilar and copy filgrastim products. METHODS: Innovator filgrastim product,
      Neupogen(r), two EU-licensed biosimilars, Zarzio(r) and Tevagrastim(r), and two
      copy filgrastim products, Biocilin(r) and PDgrastim(r), were subjected to peptide
      mapping, circular dichroism spectroscopy, fluorescence spectroscopy, sodium
      dodecyl sulfate polyacrylamide gel electrophoresis, high performance size
      exclusion chromatography, reversed-phase ultra-performance liquid chromatography,
      endotoxin test, flow imaging microscopy and in vitro potency assay. RESULTS:
      Zarzio(r) and Tevagrastim(r) have comparable quality to Neupogen(r), while
      Biocilin(r) showed a significantly lower and PDgrastim(r) a higher specific
      activity. Moreover, PDgrastim(r) showed a higher level of impurities and a lower
      thermo stability than the other products. CONCLUSIONS: Except for the deviating
      specific activities of the two copy filgrastim products, we found no substantial
      differences in product quality between the filgrastim products studied.

PMID- 30280278
TI  - Evaluation of the air pollution in a Mediterranean region by the air quality
      index.
AB  - The increasing expansion of the cities together with activities carried out on
      the environment by men have contributed to the deterioration of air quality. Air
      quality index measures how much air is free from pollution. Being aware of the
      healthiness of the breathed air is a right for the people. Public authorities
      must constantly inform the population on air quality status. Even though several
      pollutants are monitored by the air quality monitoring networks, providing a
      significant amount of data, their interpretation and presentation to the
      population by the public authorities is a difficult task. Some countries, for
      several years, have adopted evaluation procedures through daily indices that
      succinctly describe the air quality status in different areas of the city. The
      use of an index which is able to give a simple and quick information to the
      population represents a possible solution for the public authorities. Concerning
      a Mediterranean area, it has not yet been possible to adopt a single indicator to
      be used for informing the population. In this work, the air quality status is
      highlighted by the air quality index (AQI) whose purpose is to inform, in a
      simple and immediate way, the population. Analyzing the AQI's trend from 2013 to
      2015, it was possible to assess the air quality status, obtaining an overall
      scenario for the purpose of protecting human health and the ecosystems. We point
      out that this kind of research could be applied to every region or municipality.

PMID- 30280280
TI  - Clinical cases and metaphysical theories of personal identity.
AB  - In this article, we consider three metaphysical theories of personal identity:
      the soul theory, the body theory, and the psychological theory. Clinical cases
      are discussed as they present conceptual problems for each of these theories. For
      the soul theory, the case of Phineas Gage, and cases of pedophilic behavior due
      to a brain tumor are discussed. For the body theory, hypothetical cases of
      cephalosomatic anastomosis and actual cases of dicephalic parapagus and
      craniopagus parasiticus are discussed. For the psychological theory, cases of
      delusions and memory impairments are discussed. After a discussion of all these
      cases, we conclude that it is very difficult to unequivocally favor one of these
      theories, yet we argue that this discussion must be based not on abstract
      armchair speculation, but rather, consideration of real clinical cases.

PMID- 30280279
TI  - Can We Re-Engineer the Endocrine Pancreas?
AB  - PURPOSE OF REVIEW: Engineering endocrine pancreatic tissue is an emerging topic
      in type 1 diabetes with the intent to overcome the current limitation of beta
      cell transplantation. During islet isolation, the vascularized structure and
      surrounding extracellular matrix (ECM) are completely disrupted. Once implanted,
      islets slowly engraft and mostly are lost for the initial avascular phase. This
      review discusses the main building blocks required to engineer the endocrine
      pancreas: (i) islet niche ECM, (ii) islet niche vascular network, and (iii) new
      available sources of endocrine cells. RECENT FINDINGS: Current approaches include
      the following: tissue engineering of endocrine grafts by seeding of native or
      synthetic ECM scaffolds with human islets, vascularization of native or synthetic
      ECM prior to implantation, vascular functionalization of ECM structures to
      enhance angiogenesis after implantation, generation of engineered animals as
      human organ donors, and embryonic and pluripotent stem cell-derived endocrine
      cells that may be encapsulated or genetically engineered to be immunotolerated.
      Substantial technological improvements have been made to regenerate or engineer
      endocrine pancreatic tissue; however, significant hurdles remain, and more
      research is needed to develop a technology to integrate all components of viable
      endocrine tissue for clinical application.

PMID- 30280281
TI  - Limit to steady-state aerobic power of skeletal muscles.
AB  - Like any other kind of cell, muscle cells produce energy by oxidizing the fuel
      substrate that they absorb together with the needed oxygen from the surroundings.
      Oxidation occurs entirely within the cell. It means that the reactants and
      products of reaction must at some time be dissolved in the cell's cytosol. If a
      cell operates at steady state, its cytosol composition remains constant.
      Therefore, the cytosol in a muscle that produces work at steady state must
      contain a constant amount of fuel, oxygen, and product of reaction dissolved in
      it. The greater the power produced, the higher the concentration of these
      solutes. There is a limit, however, to the maximum amount of solutes that the
      cytosol can contain without damaging the cell. General thermodynamic arguments,
      which are reviewed in this paper, help relate this limit to the dehydration and
      overhydration limits of the cell. The present analysis shows that the same limits
      entail a limit to the maximum power that a muscle can produce at steady state.
      This limit depends on the composition of the fuel mixture used by the muscle. The
      analysis also determines the number of fuel carbon atoms that must be oxidized in
      parallel within a cell to produce a given power. It may well happen that a muscle
      cannot reach the maximum attainable power because it cannot activate all the
      parallel oxidation paths that are needed to produce it. This may be due to a
      series of reasons ranging from health issues to a lack of training. The paper
      shows how the methods of indirect calorimetry can provide all the experimental
      data needed to determine the actual number of parallel oxidation paths that at
      steady state must be active in a muscle in a given exercise. A diagram relating
      muscle power to the number of parallel oxidation paths and fuel composition is
      finally presented. It provides a means to assess the power capacity of animal
      muscles and can be applied to evaluate their fitness, stamina, margins for
      improvement, and athletic potential.

PMID- 30280283
TI  - Correction to: Medical Treatment Options for Patients with Epidermal Growth
      Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer Suffering from Brain
      Metastases and/or Leptomeningeal Disease.
AB  - Enhanced digital features were retrospectively added to this article.

PMID- 30280282
TI  - Detection of lncRNA-mRNA interaction modules by integrating eQTL with weighted
      gene co-expression network analysis.
AB  - One major function of lncRNA is to regulate the expression of mRNA, but the
      patterns of their interactions were largely unknown. We attempted to construct
      lncRNA-mRNA interaction modules at a genome-wide scale. We performed a genome
      wide lncRNA-mRNA eQTL analysis in peripheral blood mononuclear cells of 43
      individuals, followed by weighted gene co-expression network analysis and
      functional enrichment analysis which sought to detect functional modules. There
      were 4627 significant cis lnc-eQTL pairs (P < 1.4 * 10-6) and 1,587,128
      significant trans lnc-eQTL pairs (P < 3.46 * 10-9). We detected 11 eQTL modules
      for the lnc-eQTL networks. Among them, five modules showed significant
      enrichments in GO terms, and three modules showed significant enrichments in
      specific KEGG pathways (e.g., Toll-like receptor, PI3K-Akt, NF-kappa B, and TNF
      signaling pathways). lncRNA-protein interaction analysis showed that some well
      known functional lncRNAs (HOTAIR, CCDC26, RHPN1-AS1, WT1-AS, and TCL6) in the
      eQTL module interacted with genes in focal adhesion and PI3K-Akt signaling
      pathway. We identified biologically functional lncRNA-mRNA interaction modules by
      integrating eQTL and weighted gene co-expression network analysis. Integrative
      analysis of lncRNA and mRNA data by applying eQTL analysis and weighted gene co
      expression network analysis methods could be helpful for functional annotation of
      lncRNAs.

PMID- 30280284
TI  - Endocrine paraneoplastic syndromes in patients with neuroendocrine neoplasms.
AB  - OBJECTIVE: Our aim was to assess the prevalence of endocrine paraneoplastic
      syndromes (EPNS) in neuroendocrine neoplasms (NENs) and estimate its impact on
      patient outcomes. DESIGN: This is a retrospective analysis of 834 patients with
      NENs (611 gastrointestinal, 166 thoracic, 57 of unknown and various other primary
      origin). We included 719 consecutive NEN patients treated at EKPA-Laiko Hospital,
      Athens, Greece and 115 patients with lung carcinoid (LC) treated at Uppsala
      University Hospital, Uppsala, Sweden. EPNS diagnosis was based on standard
      criteria. METHODS: Twenty-one patients with EPNS were detected: 16 with ectopic
      Cushing's syndrome (ECS), one with hypercalcaemia due to parathyroid hormone
      related protein (PTHrP) secretion, three with hypercalcitonaemia and one patient
      with dual secretion of calcitonin and beta-human chorionic gonadotropin (beta
      HCG). All tumours were well-differentiated; 10 patients had Stage IV disease at
      diagnosis. RESULTS: The prevalence of EPNS in the Greek cohort was 1.9%, whereas
      that of ECS among LC patients in both centres was 6.7%. Median overall survival
      (OS) for patients with EPNS was 160.7 months (95%CI, 86-235.4) and median event
      free survival (EFS) was 25.9 months (95%CI, 0-57.2). Patients presenting with
      EPNS prior to NEN diagnosis had longer EFS compared to patients with synchronous
      or metachronous EPNS (log-rank P = 0.013). Patients with ECS of extra-thoracic
      origin demonstrated shorter OS and EFS compared to patients with ECS of lung or
      thymic origin (log-rank P = 0.001 and P < 0.001, respectively). LC patients with
      and without ECS were comparable in 5-year and 10-year OS rates (66.7% and 33.3%
      versus 89.8% and 60.2%, respectively; 95%CI [189.6-300.4 months], log-rank P =
      0.94) and in median EFS, 67 versus 183 months, 95%CI [50.5-207.5], log-rank P =
      0.12). CONCLUSION: EPNS are relatively rare in patients with NENs and mainly
      concern well-differentiated tumours of the foregut. Among patients with EPNS, LC
      related ECS may not adversely affect patient outcomes when diagnosed prior to NEN
      and effectively been treated.

PMID- 30280285
TI  - Gallic acid activates hippocampal BDNF-Akt-mTOR signaling in chronic mild stress.
AB  - Gallic acid (3,4,5-trihydroxybenzoic acid) is a naturally occurring polyphenolic
      compound. Previous study has shown that gallic acid possessed significant
      antidepressant-like activity in mice, which was partly mediated by increasing
      serotonin and catecholamine levels. The main aim of the present study is to
      investigate the possible effects of gallic acid on brain-derived neurotrophic
      factor (BDNF) signaling activation. Mice were exposed to chronic mild stress
      (CMS) and orally administrated with gallic acid for four weeks. The behavioral
      results showed that gallic acid not only reversed the decreased sucrose
      preference, but also attenuated the increased immobility time. In addition,
      gallic acid promoted both the BDNF and p-TrkB levels in the hippocampus induced
      by CMS. Moreover, the results also demonstrated that the inactivated Akt-mTOR
      signaling pathway, as well as its downstream effectors induced by CMS was
      activated again by gallic acid. Last, immunofluorescence detection indicated that
      gallic acid reversed the newborn neurons inhibition in the dentate gyrus by CMS.
      In conclusion, these results show that the activation of the hippocampal BDNF-Akt
      mTOR signaling is involved in the antidepressant-like effects of gallic acid.

PMID- 30280286
TI  - A Gyrolab Assay for the Quantitation of Free Complement Protein C5a in Human
      Plasma.
AB  - Complement protein C5a is recognized as an important component of the alternative
      complement pathway. Its role is prominent enough to garner interest not only as a
      biomarker, but also as a potential therapeutic target. Bioanalytical challenges
      have been posed in proper quantitation of free C5a due to interference from its
      precursor, C5. Additionally, free therapeutic target quantitation can be
      difficult due to effects of sample dilution and prolonged sample incubation when
      therapeutic is used as capture reagent. Gyrolab technology enables quantitation
      of free target analyte with minimal sample dilution and rapid sample incubations,
      thus enabling in vitro results that are more representative of in vivo
      pharmacodynamics. When coupled with strategic sample pretreatment, Gyrolab offers
      an opportunity to quantitate free C5a in human plasma with an assay that vastly
      diminishes C5 interference. A Gyrolab assay for the quantitation of free C5a in
      human plasma was developed and validated. Validation results confirmed that
      proper sample pretreatment and use of the Gyrolab platform yield accurate and
      reliable results. Due to the advantages that it provides, Gyrolab has become our
      default technology of choice for quantitation of free target.

PMID- 30280288
TI  - Bispecific Antibodies for the Treatment of Acute Myeloid Leukemia.
AB  - PURPOSE OF REVIEW: Bispecific antibodies combine antigen recognition sites from
      two or more antibodies into a single construct allowing simultaneous binding to
      multiple targets. Bispecific antibodies exist which can redirect immune effector
      cells against acute myeloid leukemia (AML) targets. This review will highlight
      the progress to date and the challenges in developing bispecific antibodies for
      the treatment of AML. RECENT FINDINGS: Currently, a number of bispecific antibody
      formats including bispecific T cell engagers, dual affinity retargeting proteins,
      and tandem diabodies are in clinical development for AML. These antibodies target
      antigens present on AML blasts, including CD33, and the low affinity IL3
      receptor, CD123. T cell redirecting bispecific antibodies in early phase clinical
      trials for AML include AG330, flotetuzumab, JNJ-63709178, and AMV564. Bispecific
      antibodies represent a promising immunotherapeutic approach for the treatment of
      cancer. The results of ongoing studies in AML will elucidate the potential for
      these agents in AML.

PMID- 30280287
TI  - Evaluation and Management of Pyogenic and Tubercular Spine Infections.
AB  - PURPOSE OF REVIEW: To review the most current diagnostic tools and treatment
      options for pyogenic and tubercular spine infection. RECENT FINDINGS: Recent
      studies have focused on risk factors for failed nonoperative management in order
      to improve patient selection. Also, spine instrumentation and different grafting
      options have been safely utilized in the setting of an active infection without
      increasing the incidence of reoccurrence. However, the optimal surgical technique
      has yet to be established and instead should be patient specific. Spine
      infections include a broad spectrum of disorders including discitis, vertebral
      osteomyelitis, and spinal epidural abscess. It is paramount to recognized spine
      infections early due to the potential catastrophic consequences of paralysis and
      sepsis. The management of spine infections continues to evolve as newer
      diagnostic tools and surgical techniques become available. Magnetic resonance
      imaging with contrast is the imaging study of choice and computed tomography
      guided biopsies are crucial for guiding antibiotic selection. Antibiotics are the
      mainstay of treatment and surgery is indicated in patients with neurological
      deficits, sepsis, spinal instability, and those who have failed nonoperative
      treatment.

PMID- 30280289
TI  - Hematopoietic Stem Cell Transplantation in the Era of Engineered Cell Therapy.
AB  - PURPOSE OF REVIEW: Cellular therapy using T cells modified to express chimeric
      antigen receptors (CAR-T cells) has had striking success in patients that have
      failed previous treatment for CD19+ B cell non-Hodgkin lymphoma (NHL), chronic
      lymphocytic leukemia (CLL), or acute lymphoblastic leukemia (ALL). Curative
      therapy for this group of diseases has previously been limited to allogeneic
      hematopoietic cell transplantation HCT (alloHCT). The recent results of CAR-T
      cell therapy raise the question of how best to integrate CAR-T cell therapy and
      alloHCT in the care of these patients. RECENT FINDINGS: Within the past 2 years,
      results from larger trials and increased follow-up of patients treated with CD19
      CAR-T cell therapy suggest that some may achieve durable remission without
      transplant. The balance of efficacy and toxicity for CAR-T cell therapy and
      alloHCT vary by disease type, disease status at the time of treatment, patient
      characteristics, and the specific therapy employed. There are early signals that
      subsequent transplantation of patients who have achieved remission with CAR-T may
      be a potentially viable (though expensive) strategy.

PMID- 30280291
TI  - Immobilization of heparin on decellularized kidney scaffold to construct
      microenvironment for antithrombosis and inducing reendothelialization.
AB  - In recent years, rapid development of tissue engineering technology provides
      possibilities for the construction of artificial tissues or organs. In
      construction of engineered kidneys, researchers used native decellularized
      extracellular matrix (ECM) as the scaffolds to recellularization. However,
      thrombosis has been a great issue that hinders the progress of transplantation in
      vivo. In this study, heparin was immobilized to the collagen part of
      decellularized scaffold with collagen-binding peptide (CBP). Through the
      anticoagulant and endothelial cell reperfusion experiments, it can be
      demonstrated that the heparinized scaffolds absorbed less platelets and red blood
      cells which can effectively reduce the formation of thrombosis. Moreover, it is
      conducive to long-term adhesion of endothelial cells which is important for the
      formation of subsequent vascularization. Taken together, our results reveal that
      the whole kidney can be modified by CBP-heparin composite to reduce the
      thrombosis and provide the better conditions for neovascularization.

PMID- 30280290
TI  - Curative and palliative surgery in patients with neuroendocrine tumors of the
      gastro-entero-pancreatic (GEP) tract.
AB  - The incidence of neuroendocrine tumors (NET) increases with age. Lately, the
      diagnosis of NET was mainly caused by early detection of small NET (<1 cm) in the
      rectum and stomach, which are depicted by chance during routine and prophylactic
      endoscopy. Also in patients with large and metastatic pancreatic and intestinal
      tumors thorough pathologic investigation with use of different immunohistologic
      markers discovers more neuroendocrine tumors with low differentiation grade (G2
      G3) and more neuroendocrine carcinomas (NEC), nowadays, than in former times.
      While gastric and rectal NET are discovered as small (<1 cm in diameter) and
      mainly highly differentiated tumors, demonstrating lymph node metastases in less
      than 10% of the patients, the majority of pancreatic and small bowel NET have
      already metastasized at the time of diagnosis. This is of clinical importance,
      since tumor stage and differentiation grade not only influence prognosis but also
      surgical procedure and may define whether a combination of surgery with systemic
      biologic therapy, chemotherapy or local cytoreductive procedures may be used. The
      indication for surgery and the preferred surgical procedure will have to consider
      personal risk factors of each patient (i.e. general health, additional illnesses,
      etc.) and tumor specific factors (i.e. tumor stage, grade of differentiation,
      functional activity, mass and variety of loco regional as well as distant
      metastases etc.). Together they define, whether radical curative or only
      palliative surgery can be applied. Altogether surgery is the only cure for
      locally advanced NET and helps to increase quality of life and overall survival
      in many patients with metastatic neuroendocrine tumors. The question of cure
      versus palliative therapy sometimes only can be answered with time, however. Many
      different aspects and various questions concerning the indication and extent of
      surgery and the best therapeutic procedure are still unanswered. Therefore, a
      close multidisciplinary cooperation of colleagues involved in biochemical and
      localization diagnostics and those active in various treatment areas is warranted
      to search for the optimal strategy in each individual patient. How far genetic
      screening impacts survival remains to be seen. Since surgeons do have a central
      role in the treatment of NET patients, they have to understand the need for
      integration into such an interdisciplinary team.

PMID- 30280292
TI  - Monitoring the Progression of Chronic Liver Damage in Rats Using [18F]PBR06.
AB  - PURPOSE: Accurate and rapid assessment of liver condition is the key to therapy
      for hepatitis patients. This study aim is to evaluate the peripheral
      benzodiazepine receptor (PBR) radioligand [18F]N-fluoroacetyl-N-(2,5
      dimethoxybenzyl)-2-phenoxyaniline ([18F]PBR06) as a positron emission tomography
      (PET) imaging tracer of chronic liver damage in a rat model. PROCEDURES: A rat
      model of liver damage was made by bile duct ligation (BDL), which initiates a
      complex cascade of pathological events that leads to cholestasis and
      inflammation, eventually resulting in a severe fibrotic and severe hepatocyte
      injury. PET scanning, immunofluorescence staining, H&E staining, Masson's
      staining, and Quantitative real time polymerase chain reaction(qRT-PCR) were
      performed to elucidate the correlation among the expression level of PBR,
      radioactivity uptake, and the level of liver damage in the rat model of chronic
      inflammatory. RESULTS: Alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), and total bilirubin (TBIL) increased after BDL and peaked in 1 week, then
      gradually decreased over the following 3 weeks, although still higher than that
      of control (all P < 0.05). Histological analysis demonstrated chronic severe
      damage in rat livers after BDL. The uptake of [18F]PBR06  increased in livers and
      was correlated with severity of liver damage. Further, the mRNA level of PBR was
      obviously higher compared to controls. CONCLUSIONS: [18F]PBR06 can serve as a
      sensitive probe to monitor the progression of inflammation in liver. [18F]PBR06
      imaging may be used to accurately assess liver damage degree and guide the
      therapeutic schedule, especially for those patients with severe liver
      inflammation and damage but with normal or mildly elevated serum ALT and AST. As
      a non-invasive diagnostic application, [18F]PBR06 PET scan could be an
      alternative for patients who is unwilling to perform liver biopsy.

PMID- 30280293
TI  - Ripor2 is involved in auditory hair cell stereociliary bundle structure and
      orientation.
AB  - RIPOR2 (previously known as FAM65B) localizes to stereocilia of auditory hair
      cells and causes deafness when its function is disturbed by mutations. Here, we
      demonstrate that during the morphogenesis of the hair cell bundle, absence of
      Ripor2 affects the orientation of this key subcellular structure. We show that
      Ripor2 interacts with Myh9, a protein encoded by a known deafness gene. Absence
      of Ripor2 is associated with low Myh9 abundance in the mouse cochlea despite
      increased amount of Myh9 transcripts. While Myh9 is mainly expressed in
      stereocilia, a phosphorylated form of Myh9 is particularly enriched in the
      kinocilium. In Ripor2-deficient mice, kinocilium shows an aberrant localization
      which associates with a reduced content of phosphorylated Myh9. Acetylated alpha
      tubulin, another specific kinociliary protein which contributes to microtubule
      stabilization, is reduced in the absence of Ripor2 as well. We propose that
      Ripor2 deficiency influences abundance and/or post-translational modifications of
      proteins expressed in both stereocilia and kinocilia. This effect may have a
      negative impact on the structure and function of the auditory hair cell bundle.

PMID- 30280295
TI  - Different Secretory Activity of Articular and Subcutaneous Adipose Tissues from
      Rheumatoid Arthritis and Osteoarthritis Patients.
AB  - Rheumatoid arthritis (RA) and osteoarthritis (OA) are characterized by joint and
      systemic high- or low-grade inflammation, respectively. Adipose tissue (AT) may
      contribute to the pathogenesis of these diseases. To address this issue, we
      investigated whether basal and pro-inflammatory cytokine (IL-1beta)-triggered
      release of adipocytokines (TNF, IL-6, IL-10, IL-1Ra, TGFbeta, CCL2/MCP-1,
      CCL5/RANTES, MMP-3) from subcutaneous (ScAT) and intraarticular (AAT) adipose
      tissues of RA and OA patients mirror differences between these diseases in an
      intensity of systemic and local inflammation. We found that in both diseases
      basal adipocytokine release was usually higher from AAT than ScAT, reflecting
      stronger local than systemic inflammation. However, ScAT secreted considerable
      amounts of pro- and anti-inflammatory factors as well. Spontaneous secretion of
      some adipocytokines (MMP-3 and/or TNF, CCL2/MCP-1, IL-1Ra) was higher in
      osteoarthritis than rheumatoid ATs and probably caused by weaker anti
      inflammatory treatment of OA patients. By contrast, reactivity of ATs to IL-1beta
      was significantly lower in OA than RA and IL-1beta antagonist (IL-1Ra) could be
      responsible for this because we found its overproduction in OA ATs.
      Interestingly, higher reactivity of ScAT than AAT to IL-1beta was a
      characteristic for OA while reactivity of rheumatoid ScAT and AAT to this
      stimulus was equal. We conclude that differences between OA and RA in reactivity
      of AAT and ScAT to pro-inflammatory stimulus mimicking in vivo condition reflect
      dissimilarity in an intensity of disease-specific inflammation and thus support
      contribution of ATs to these pathological processes. Moreover, we propose that
      more efficient anti-inflammatory mechanism(s) are preserved in ATs of OA than RA
      patients.

PMID- 30280296
TI  - LGBT+ Individuals' Perceptions of Healthcare Services in Turkey: A Cross
      sectional Qualitative Study.
AB  - When accessing healthcare services, LGBT+ individuals are often exposed to
      segregating and marginalizing discourses. Knowledge about how such experiences
      are reflected in the moral world of LGBT+ individuals living in Turkey is
      limited. This study examined LGBT+ individuals' lived experiences when utilizing
      healthcare services. The findings are discussed in terms of moral discourses
      related to LGBT+ individuals' gender identity and sexual orientation. A
      qualitative field study was conducted using semi-structured interviews with fifty
      five LGBT+ individuals from Turkish cities who were in contact with various non
      governmental organizations that conduct studies on gender identity and sexual
      orientation. A questionnaire was administered with items on participants'
      demographic information, experiences, behavioural patterns, and knowledge
      regarding healthcare services. The data were analysed thematically. The findings
      were evaluated within the framework of "access to healthcare service" theme
      related to "healthcare service demand" context. Additionally, the "interaction
      with physicians" theme was addressed in the context of "physician
      patient/counselee relationship." LGBT+ individuals state that they are exposed to
      stigmatizing and segregating discourses by healthcare professionals, which might
      pose an obstacle for adaptive health-seeking behaviours. These results suggest
      that physicians' professional approach has a considerable influence on LGBT+
      individuals' capacity for utilizing healthcare services.

PMID- 30280294
TI  - Reverse Engineering the 1-Month Lupron Depot(r).
AB  - The 1-month Lupron Depot(r) (LD) encapsulating water-soluble leuprolide in
      poly(lactic-co-glycolic acid) (PLGA) microspheres is a benchmark product upon
      which modern long-acting release products are often compared. Despite expiration
      of patent coverage, no generic product for the LD has been approved in the USA,
      likely due to the complexity of components and manufacturing processes involved
      in the product. Here, we describe the reverse engineering of the LD composition
      and important product attributes. Specific attributes analyzed for microspheres
      were as follows: leuprolide content by three methods; gelatin content, type, and
      molecular weight distribution; PLGA content, lactic acid/glycolic acid ratio, and
      molecular weight distribution; mannitol content; in vitro drug release; residual
      solvent and moisture content; particle size distribution and morphology; and
      glass transition temperature. For the diluent, composition, viscosity, and
      specific gravity were analyzed. Analyzed contents of the formulation and the
      determined PLGA characteristics matched well with the official numbers stated in
      the package insert and those found in literature, respectively. The gelatin was
      identified as type B consistent with ~ 300 bloom. The 11-MUm volume-median
      microspheres in the LD slowly released the drug in vitro in a zero-order manner
      after ~ 23% initial burst release. Very low content of residual moisture (< 0.5%)
      and methylene chloride (< 1 ppm) in the product indicates in-water drying is
      capable of removing solvents to extremely low levels during manufacturing. The
      rigorous approach of reverse engineering described here may be useful for
      development of generic leuprolide-PLGA microspheres as well as other new and
      generic PLGA microsphere formulations.

PMID- 30280297
TI  - Critical biochemistry values and patient safety in primary care.

PMID- 30280298
TI  - Investigation by Fluorescence Technique of the Quenching Effect of Co2+ and Mn2+
      Transition Metals, on Naphthalene-Methyl-Beta-Cyclodextrin Host-Guest Inclusion
      Complex.
AB  - Inclusion complex of naphthalene with methyl-beta-cyclodextrin in water has been
      formed. The aqueous solutions of the various amounts of Co2+ve Mn2+salts have
      been added to naphthalene-methyl-beta-cyclodextrin (NAP-Me-beta-CD) inclusion
      complexes. Fluorescence properties of the naphthalene (NAP) compound have been
      utilized to observe the changes in fluorescence intensities. Stern-Volmer
      quenching constants and fluorescence quantum yields have been calculated.
      Characterization of the resulting complex by FT-IR and 1H NMR technique has been
      determined. Fluorescence lifetime measurements have been made in the presence and
      absence of the quenching reagent and Gibbs free energy change has been
      calculated.

PMID- 30280299
TI  - Prediction of femtosecond laser ablation profile on human teeth.
AB  - To predict the laser ablation profile on dental hard tissue which will enable the
      user to optimize laser parameters so as to carry out the laser treatment with
      minimal tissue damage. The present study constructs a mathematical model to
      predict the ablation profile based on Gaussian beam distribution of laser
      intensity and correlates the model with experimentally obtained ablation
      parameters (effective Gaussian beam radius, ablation threshold fluence, and
      effective energy penetration depth). To obtain the ablation parameters, laser
      ablation experiments were carried out on dental hard tissues using Ti:Sapphire
      femtosecond laser (800 nm, 100 fs, 10 kHz). The method is further extended to
      predict the ablation rate and efficiency as well. The profile predicted from the
      mathematical model is compared with that of experimental results. It is found
      that the predicted ablation profile agrees well with the experimental profile for
      both enamel and dentin except a slight deviation at higher fluence for dentin.
      The calculated ablation rate is comparable to that of experimental results
      whereas for ablation efficiency appreciable deviation is observed in the case of
      dentin. The model succinctly predicts the ablation profile, ablation rate, and
      ablation efficiency which will enable to perform dental surgery at optimized
      laser processing conditions with high precision thus reducing the tissue damage
      appreciably. Once the details of lesion are known through proper diagnostic
      tools, the method enables the user to readily obtain optimum laser parameters. It
      can be used as a handy reference for dentists to perform damage-free surgery,
      ensuring quicker healing.

PMID- 30280300
TI  - Quantitative evaluation of skin shrinkage associated with non-invasive skin
      tightening: a simple method for reproducible linear measurement using
      microtattoos.
AB  - Non-invasive skin-tightening devices can induce thermal denaturation and skin
      shrinkage via externally applied radiofrequency emissions or high-frequency
      ultrasound. Therefore, the purpose of this study is to develop and test a method
      for measurement of skin reduction associated with application of such energy
      devices. Twenty-five healthy participants with mild to moderate skin laxity of
      the arms were enrolled. Pinpoint microtattoos were placed at each of the
      treatment sites to delineate two 6 * 12 cm rectangles per subject. A non
      stretchable filament, tape and marking pen apparatus was used to measure the size
      of each rectangle before treatment and at follow-up visit by two blinded
      investigators. After randomization, one side received a single pass with a
      radiofrequency device (6.78 MHz), while the contralateral side received multiple
      passes. Participants underwent two treatment sessions to each side 2 weeks apart,
      and returned for follow-up 4 weeks after the second treatment. Length and area
      measurement were analyzed to assess precision and accuracy of measurements and to
      compare efficacy of treatment between pre- and post-treatment. Concordance
      correlation coefficients (CCC) demonstrated substantial inter-investigator
      reliability and precision in length measurements (CCC, 0.94 to 0.98 in pre
      treatment; 0.95 to 0.98 in post-treatment). Measurements at the 6-week post
      treatment follow-up demonstrated a statistically significant skin reduction in
      all six of the measured parameters. A simple skin measurement method requiring
      minimal instrumentation can quantitatively evaluate skin shrinkage associated
      with non-invasive skin-tightening devices.

PMID- 30280301
TI  - Stochastic Modelling of Air Pollution Impacts on Respiratory Infection Risk.
AB  - The impact of air pollution on people's health and daily activities in China has
      recently aroused much attention. By using stochastic differential equations,
      variation in a 6 year long time series of air quality index (AQI) data, gathered
      from air quality monitoring sites in Xi'an from 15 November 2010 to 14 November
      2016 was studied. Every year the extent of air pollution shifts from being
      serious to not so serious due to alterations in heat production systems. The
      distribution of such changes can be predicted by a Bayesian approach and the
      Gibbs sampler algorithm. The intervals between changes in a sequence indicate
      when the air pollution becomes increasingly serious. Also, the inflow rate of
      pollutants during the main pollution periods each year has an increasing trend.
      This study used a stochastic SEIS model associated with the AQI to explore the
      impact of air pollution on respiratory infections. Good fits to both the AQI data
      and the numbers of influenza-like illness cases were obtained by stochastic
      numerical simulation of the model. Based on the model's dynamics, the AQI time
      series and the daily number of respiratory infection cases under various
      government intervention measures and human protection strategies were forecasted.
      The AQI data in the last 15 months verified that government interventions on
      vehicles are effective in controlling air pollution, thus providing numerical
      support for policy formulation to address the haze crisis.

PMID- 30280302
TI  - Occupational and patient radiation doses in a modern cardiac electrophysiology
      laboratory.
AB  - PURPOSE: Technological advancements have greatly expanded the field of cardiac
      electrophysiology, requiring greater demands on imaging systems and potentially
      delivering higher radiation doses to patients and operators. With little
      contemporary research on occupational and patient radiation risk in the
      electrophysiology laboratory, the aim of this study was to analyze radiation
      doses, including occupational fetal doses, over approximately the last decade. We
      benchmarked the occupational data to our patient radiation dose data to allow for
      comparison and to put into perspective the associated radiation risks. METHODS:
      Occupational radiation dosimetry analyzed included data from an 11-year period
      for physicians, a 7-year period for nurses, and a 9-year period for fetal doses.
      Patient-related dose metrics over an 8-year period were also analyzed. RESULTS:
      In the physician and nursing groups, there was a nearly 70% decrease in the
      average occupational radiation doses over the given periods. Within the
      electrophysiology department, the average fetal occupational doses were very low,
      close to 0 MUSv. The average reference point air kerma per patient for all
      electrophysiology procedures decreased from nearly 600 mGy/procedure in 2010 to
      just over 100 mGy/procedure in 2017. CONCLUSIONS: Patient and occupational
      radiation doses in our laboratories significantly decreased over the periods
      analyzed as a result of clinical and technical staff efforts as well as advances
      in imaging technology. The radiation-related risk to individuals working in our
      electrophysiology laboratories, including pregnant women, is very low. Data
      reported herein could be used by other institutions to evaluate their
      occupational and patient radiation safety practices.

PMID- 30280303
TI  - Idiopathic ventricular arrhythmias arising from the posterior septum of tricuspid
      and mitral annuli: comparison of electrocardiographic characteristics and
      outcomes of catheter ablation.
AB  - PURPOSE: Ventricular arrhythmia (VA) arising from the tricuspid annulus in the
      posterior septum (PS) (TAPS-VA) has similar electrocardiographic characteristics
      as VA arising from the mitral annulus in the PS (MAPS-VA) because the two
      locations are adjacent. We examined the electrocardiographic characteristics that
      differentiate MAPS-VA from TAPS-VA and the efficacy of catheter ablation.
      METHODS: We studied 13 patients whose VAs were successfully ablated in the TAPS
      (n = 7) and MAPS (n = 6). RESULTS: QRS morphologies of both groups were
      characterized by left and right bundle block morphologies in lead V1, superior
      axis deviation, and precordial transition at <= lead V3 in nine patients.
      Compared with TAPS-VA, MAPS-VA had (1) R < S wave in lead II, (2) precordial
      transition in lead V2, (3) s-wave in lead V6, and (4) slurred initial part of the
      QRS complex in the precordial leads, e.g., [4a] pseudo delta wave >= 34 ms, [4b]
      intrinsicoid deflection time >= 85 ms, and [4c] maximum deflection index >= 0.55.
      Patients who met >= 2 of (1)-(3) and any of [4a]-[4c] could be classified as
      having MAPS-VA, with a sensitivity and specificity of 100%. VA recurred in one
      patient in the TAPS group during the median follow-up of 7 (interquartile range 6
      to 15.5) months. CONCLUSIONS: VA arising from the PS has superior axis deviation,
      and left and right bundle block morphologies with relatively early precordial
      transition. MAPS-VA can be differentiated from TAPS-VA based on
      electrocardiographic characteristics. This study provides useful information for
      treatment involving catheter ablation for VA arising from the PS.

PMID- 30280304
TI  - Machine learning approach to identify a resting-state functional connectivity
      pattern serving as an endophenotype of autism spectrum disorder.
AB  - Endophenotype refers to a measurable and heritable component between genetics and
      diagnosis, and the same endophenotype is present in both individuals with a
      diagnosis and their unaffected siblings. Determination of the neural correlates
      of an endophenotype and diagnosis is important in autism spectrum disorder (ASD).
      However, prior studies enrolling individuals with ASD and their unaffected
      siblings have generally included only one group of typically developing (TD)
      subjects; they have not accounted for differences between TD siblings. Thus, they
      could not differentiate the neural correlates for endophenotype from the clinical
      diagnosis. In this context, we enrolled pairs of siblings with an ASD
      endophenotype (individuals with ASD and their unaffected siblings) and pairs of
      siblings without this endophenotype (pairs of TD siblings). Using resting-state
      functional MRI, we first aimed to identify an endophenotype pattern consisting of
      multiple functional connections (FCs) then examined the neural correlates of FCs
      for ASD diagnosis, controlling for differences between TD siblings. Sparse
      logistic regression successfully classified subjects as to the endophenotype
      (area under the curve = 0.78, classification accuracy = 75%). Then, a
      bootstrapping approach controlling for differences between TD siblings revealed
      that an FC between the right middle temporal gyrus and right anterior cingulate
      cortex was substantially different between individuals with ASD and their
      unaffected siblings, suggesting that this FC may be a neural correlate for the
      diagnosis, while the other FCs represent the endophenotype. The current findings
      suggest that an ASD endophenotype pattern exists in FCs, and a neural correlate
      for ASD diagnosis is dissociable from this endophenotype. (250 words).

PMID- 30280305
TI  - Treatment of Hereditary Angioedema Attacks with Icatibant and Recombinant C1
      Inhibitor During Pregnancy.
AB  - PURPOSE: Hereditary angioedema (HAE) is a rare disease caused by a C1 inhibitor
      (C1-INH) deficit. Clinically, HAE is manifested by repeated episodes of localized
      subcutaneous or submucosal oedema attacks. Managing HAE patients in pregnancy is
      challenging, since there are only limited data on the safety and efficacy of
      various therapeutic approaches. METHODS: We present our clinical experience
      treating acute HAE attacks during pregnancy in six consecutive patients. RESULTS:
      During the pregnancies, 79 HAE attacks occurred. The most frequent were abdominal
      53 (67.1%) followed by peripheral 21 (26.6%), facial 10 (12.7%), and laryngeal 10
      (12.7%) oedemas; 13 (16.5%) attacks were combined. Fifty (63.3%) attacks were
      treated with recombinant human C1-INH (rhC1-INH); 17 (21.5%) with plasma-derived,
      pasteurized, nanofiltered C1-INH (pnfC1-INH); 13 (16.5%) with icatibant; and 1
      (1.3%) with plasma-derived, nanofiltered C1-INH (nfC1-INH). Treatment had to be
      repeated in 5 attacks (6.3%). All six deliveries (one caesarean section and five
      spontaneous vaginal deliveries) were complication free. All pregnancies went to
      the full term and the patients delivered healthy babies with a birth weight
      ranging from 2850 to 3690 g. No congenital abnormalities were detected in the
      neonates. No abortions occurred. CONCLUSIONS: Our results show good C1-INH or
      icatibant treatment efficacy for HAE attacks in pregnancy. The treatment by the
      first drug used was effective in 93.7% of all attacks. In 6.3% of attacks, a
      second treatment had to be used. No adverse effects were observed.

PMID- 30280306
TI  - Pseudo-Sarcoidosis Revealing MonoMAC Syndrome.

PMID- 30280307
TI  - Histone variants: critical determinants in tumour heterogeneity.
AB  - Malignant cell transformation could be considered as a series of cell
      reprogramming events driven by oncogenic transcription factors and upstream
      signalling pathways. Chromatin plasticity and dynamics are critical determinants
      in the control of cell reprograming. An increase in chromatin dynamics could
      therefore constitute an essential step in driving oncogenesis and in generating
      tumour cell heterogeneity, which is indispensable for the selection of aggressive
      properties, including the ability of cells to disseminate and acquire resistance
      to treatments. Histone supply and dosage, as well as histone variants, are the
      best-known regulators of chromatin dynamics. By facilitating cell reprogramming,
      histone under-dosage and histone variants should also be crucial in cell
      transformation and tumour metastasis. Here we summarize and discuss our knowledge
      of the role of histone supply and histone variants in chromatin dynamics and
      their ability to enhance oncogenic cell reprogramming and tumour heterogeneity.

PMID- 30280308
TI  - Epidemic obesity in children and adolescents: risk factors and prevention.
AB  - The prevalence of obesity among children and adolescents (aged 2-18 years) has
      increased rapidly, with more than 100 million affected in 2015. Moreover, the
      epidemic of obesity in this population has been an important public health
      problem in developed and developing countries for the following reasons.
      Childhood and adolescent obesity tracks adulthood obesity and has been implicated
      in many chronic diseases, including type 2 diabetes, hypertension, and
      cardiovascular disease. Furthermore, childhood and adolescent obesity is linked
      to adulthood mortality and premature death. Although an imbalance between caloric
      intake and physical activity is a principal cause of childhood and adolescent
      obesity, environmental factors are exclusively important for development of
      obesity among children and adolescents. In addition to genetic and biological
      factors, socioenvironmental factors, including family, school, community, and
      national policies, can play a crucial role. The complexity of risk factors for
      developing obesity among children and adolescents leads to difficulty in
      treatment for this population. Many interventional trials for childhood and
      adolescent obesity have been proven ineffective. Therefore, early identification
      and prevention is the key to control the global epidemic of obesity. Given that
      the proportion of overweight children and adolescents is far greater than that of
      obesity, an effective prevention strategy is to focus on overweight youth, who
      are at high risk for developing obesity. Multifaceted, comprehensive strategies
      involving behavioral, psychological, and environmental risk factors must also be
      developed to prevent obesity among children and adolescents.

PMID- 30280309
TI  - Iodine Nutrition and Thyroid Function in Pregnant Women Exposed to Different
      Iodine Sources.
AB  - Pregnant women are more vulnerable to iodine deficiency and iodine excess. The
      study aimed to assess the changes in iodine nutrition and thyroid function of
      pregnant women exposed to different iodine sources resulting in various iodine
      intakes during pregnancy. From 2016 to 2017, 2004 healthy pregnant women aged 20
      35 years from Shandong and Tianjin, China, were enrolled. Urinary iodine
      concentration (UIC), drinking water iodine content (WIC), thyroid-stimulating
      hormone (TSH), free triiodothyronine (FT3), free thyroid hormone (FT4),
      thyroglobulin (Tg), serum thyroid peroxidase antibody (TPOAb), and thyroglobulin
      antibody (TgAb) were measured. Pregnant women in both Shandong and Tianjin were
      iodine sufficient, but the median UIC in pregnant women was significantly higher
      in Shandong (244 MUg/L) than that in Tianjin (159 MUg/L). No differences were
      found in UIC over the course of gestation in Shandong. In Tianjin, the UIC
      decreased during 13-24 weeks and stabilized thereafter. Compared with Tianjin,
      TSH levels were higher and FT3 and FT4 levels were lower in Shandong. Both FT3
      and FT4 significantly decreased during pregnancy in Shandong and Tianjin. TSH and
      Tg increased over the course of gestation in both Shandong and Tianjin. The
      iodine status of pregnant women in Tianjin and Shandong were sufficient, but
      different changing patterns in UIC and thyroid function during pregnancy were
      presented. More attention should be focused on iodine nutrition of pregnant
      women, even in iodine-sufficient areas.

PMID- 30280310
TI  - Impact of fixation, coil, and number of excitations on diffusion tensor imaging
      of rat brains at 7.0 T.
AB  - BACKGROUND: We sought to compare diffusion tensor imaging (DTI) parameters in
      vivo and ex vivo in the brain and to explore the effects of radiofrequency coil
      and number of excitations on ex vivo DTI parameters. METHODS: Six Sprague-Dawley
      rat brains were used to obtain in vivo and ex vivo DTI maps with different coils
      and number of excitations. DTI parameters of white matter and grey matter
      including diffusivities, fractional anisotropy, and other dimensionless ratios
      (lambda2/lambda1, lambda3/lambda1, and lambda2/lambda3) were obtained from
      reconstruction maps. Comparisons of ex vivo signal-to-noise ratio with different
      coils and number of excitations were conducted. RESULTS: Diffusivities decreased
      significantly after fixation in all the selected white matter and grey matter
      regions of interest (all at p < 0.001). The diffusivities in white matter
      integrity decreased more than in grey matter integrity after fixation (all at p <
      0.001). The ratio of lambda2/lambda3 in the major brain structures changed after
      fixation (most at p < 0.05). There were differences in major ex vivo brain
      structures in DTI parameters and signal-to-noise ratio between surface coil and
      volume coil, and between one and four excitations (most at p < 0.05). CONCLUSION:
      The impact of fixation, coil, and number of excitations on DTI parameters should
      be taken into consideration in clinical and experimental studies at 7.0 T.

PMID- 30280311
TI  - In vitro comparison of microleakge between preformed metal crowns and aesthetic
      crowns of primary molars using different adhesive luting cements.
AB  - AIM: To assess and compare the microleakage extent between preformed metal crowns
      (PMCs), preveneered PMCs and zirconia crowns using different adhesive luting
      cements. METHODS: Thirty-six primary first molars were divided into three groups
      (n = 12) each prepared to receive different crowns (PMCs, preveneered PMCs, or
      zirconia crowns). Each group was further sub-grouped (n = 4) according to the
      luting cement (resin cement, resin modified glass ionomer cement, or glass
      ionomer cement). After cementation, the teeth were thermocycled, placed in 0.5%
      basic fuchsin, and sectioned to assess dye penetration. The results were analysed
      using ANOVA and Bonferroni statistical tests. The level of significance was set
      at p < 0.05. RESULTS: The microleakage recorded in zirconia crowns was
      significantly worse than that in preveneered PMCs and PMCs (p < 0.001).
      Regardless of the crown type, resin cement resulted in the least microleakage
      with statistically significant differences from glass ionomer cement (p < 0.05).
      CONCLUSIONS: As far as microleakage is concerned, preveneered PMCs seem to be an
      aesthetic and suitable alternative to PMCs. In addition, resin cement stands to
      be the most optimum luting cement.

PMID- 30280312
TI  - Sodium acetate improves disrupted glucoregulation and hepatic triglyceride
      content in insulin-resistant female rats: involvement of adenosine deaminase and
      dipeptidyl peptidase-4 activities.
AB  - Combined oral contraceptive (COC) treatment has been shown to be associated with
      glucose deregulation and increased triglyceride levels, but the mechanisms are
      elusive. Soluble dipeptidyl peptidase-4 (sDPP-4) and adenosine deaminase (ADA)
      are involved in the initiation and/or progression of cardiometabolic disorders.
      We therefore, hypothesized that increased DPP-4 and ADA activities are involved
      in glucose deregulation and hepatic triglyceride accumulation induced by COC
      treatment. This study also investigated whether short-chain fatty acid, acetate,
      would protect against COC-induced dysmetabolic effects. Female Wistar rats
      received (p.o.) vehicle and COC (1.0 MUg ethinylestradiol plus 5.0 MUg
      levonorgestrel) with or without sodium acetate (ACE; 200 mg) for 8 weeks.
      Treatment with COC led to increased plasma triglyceride-glucose index, 1-h
      postload glucose response, insulin, free fatty acid, insulin resistance, and
      impaired glucose tolerance. COC treatment also resulted in increased plasma and
      hepatic triglycerides (TG), TG/HDL-cholesterol ratio, malondialdehyde, uric acid,
      lactate dehydrogenase, DPP-4, ADA, and xanthine oxidase (XO) activities. On the
      other hand, COC led to reduction in nitric oxide level. However, ACE
      significantly ameliorated the alterations induced by COC treatment, but XO
      activity remains elevated during COC treatment. This result also demonstrates
      that increased DPP-4 and ADA activities are at least in part involved in glucose
      deregulation and hepatic TG accumulation induced by COC treatment. Therefore,
      sodium acetate would impact positively on cardiometabolic disorders, at least in
      part, by inhibition of DPP-4 and ADA activities.

PMID- 30280315
TI  - Quantitative Evaluation of Native Protein Folds and Assemblies by Hydrogen
      Deuterium Exchange Mass Spectrometry (HDX-MS).
AB  - Hydrogen deuterium exchange mass spectrometry (HDX-MS) has significant potential
      for protein structure initiatives but its relationship with protein conformations
      is unclear. We report on the efficacy of HDX-MS to distinguish between native and
      non-native proteins using a popular approach to calculate HDX protection factors
      (PFs) from protein structures. The ability of HDX-MS to identify native protein
      conformations is quantified by binary structural classification such that merits
      of the approach for protein modelling can be quantified and better understood. We
      show that highly accurate PF calculations are not a prerequisite for HDX-MS
      simulations that are capable of effectively discriminating between native and non
      native protein folds. The simulations can also be performed directly on unique
      structures facilitating high-throughput evaluation of many alternate
      conformations. The ability of HDX-MS to classify the conformations of homo
      protein assemblies is also investigated. In contrast to protein monomers, we show
      a significant lack of correspondence between the simulated and experimental HDX
      MS data for these systems with a subsequent decrease in the ability of HDX-MS to
      identify native states. However, we demonstrate surprisingly high diagnostic
      ability of the simulated data for assemblies in which a significant proportion of
      the individual chains occupy protein-protein interfaces. We relate this to the
      number of peptides that can sample alternate subunit orientations and discuss
      these observations within the larger context of applying HDX-MS to evaluate
      protein structures. Graphical Abstract.

PMID- 30280314
TI  - On-substrate Enzymatic Reaction to Determine Acetylcholinesterase Activity in
      Whole Blood by Paper Spray Mass Spectrometry.
AB  - Currently, all assays measuring acetylcholinesterase (AChE) activity following a
      suspected nerve agent exposure leverage methodologies that fail to identify the
      agent. This limits the overall effectiveness and ability to administer proper
      countermeasures. As such, there is an urgent need to identify novel, rapid, and
      more comprehensive approaches to establish AChE activity, including
      identification of the toxicant. Paper spray mass spectrometry was used to monitor
      the activity of acetylcholinesterase, both in-solution and on modified
      hydrophobic paper surface. Hydrophobic paper surfaces were prepared using
      vaporized trichloro(3,3,3-trifluoropropyl)silane. In both approaches, mixtures of
      diluted human whole blood with and without VX were mixed with a non-endogenous
      AChE specific substrate, 1,1-dimethyl-4-acetylthiomethylpiperidinium (MATP+).
      Formation of the cleaved MATP+ product was monitored over time and compared to
      MATP+ to determine relative AChE activity. This on-substrate assay was effective
      at determining AChE activity and identifying the toxicant; however, determination
      of AChE activity in-solution proceeded at a slower rate. The on-substrate assay
      serves as a pioneering example of an enzymatic reaction occurring on the surface
      of a paper spray ionization ticket. This work broadens the range of applications
      relating to paper spray ionization-based clinical diagnostic assays. Graphical
      Abstract ?.

PMID- 30280316
TI  - Early life stress and trauma: developmental neuroendocrine aspects of prolonged
      stress system dysregulation.
AB  - Experience of early life stress (ELS) and trauma is highly prevalent in the
      general population and has a high public health impact, as it can trigger a
      health-related risk cascade and lead to impaired homeostatic balance and elevated
      cacostatic load even decades later. The prolonged neuropsychobiological impact of
      ELS can, thus, be conceptualized as a common developmental risk factor for
      disease associated with increased physical and mental morbidity in later life.
      ELS during critical periods of brain development with elevated neuroplasticity
      could exert a programming effect on particular neuronal networks related to the
      stress response and lead to enduring neuroendocrine alterations, i.e., hyper- or
      hypoactivation of the stress system, associated with adult hypothalamic-pituitary
      adrenal axis and glucocorticoid signaling dysregulation. This paper reviews the
      pathophysiology of the human stress response and provides evidence from human
      research on the most acknowledged stress axis-related neuroendocrine pathways
      exerting the enduring adverse effects of ELS and mediating the cumulative long
      term risk of disease vulnerability in adulthood.

PMID- 30280313
TI  - Chinese guidelines for the diagnosis and treatment of hand, foot and mouth
      disease (2018 edition).
AB  - BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common infectious disease
      in childhood caused by an enterovirus (EV), and which is principally seen in
      children under 5 years of age. To promote diagnostic awareness and effective
      treatments, to further standardize and strengthen the clinical management and to
      reduce the mortality of HFMD, the guidelines for diagnosis and treatment have
      been developed. METHODS: National Health Commission of China assembled an expert
      committee for a revision of the guidelines. The committee included 33 members who
      are specialized in diagnosis and treatment of HFMD. RESULTS: Early recognition of
      severe cases is utmost important in diagnosis and treatment of patients with
      HFMD. The key to diagnosis and treatment of severe cases lies in the timely and
      accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to
      stage 4. Clinicians should particularly pay attention to those EV-A71 cases in
      children aged less than 3 years, and those with disease duration less than 3
      days. The following indicators should alert the clinician of possible
      deterioration and impending critical disease: (1) persistent hyperthermia; (2)
      involvement of nervous system; (3) worsening respiratory rate and rhythm; (4)
      circulatory dysfunction; (5) elevated peripheral WBC count; (6) elevated blood
      glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be
      treated as outpatients. Patients should be isolated to avoid cross-infection.
      Intense treatment modalities should be given for those severe cases. CONCLUSION:
      The guidelines can provide systematic guidance on the diagnosis and management of
      HFMD.

PMID- 30280317
TI  - Environmental Selenium and Human Health: an Update.
AB  - PURPOSE OF REVIEW: Selenium, a trace element, is ubiquitous in the environment.
      The main source of human exposure is diet. Despite its nutritional benefits, it
      is one of the most toxic naturally occurring elements. Selenium deficiency and
      overexposure have been associated with adverse health effects. Its level of
      toxicity may depend on its chemical form, as inorganic and organic species have
      distinct biological properties. RECENT FINDINGS: Nonexperimental and experimental
      studies have generated insufficient evidence for a role of selenium deficiency in
      human disease, with the exception of Keshan disease, a cardiomyopathy.
      Conversely, recent randomized trials have indicated that selenium overexposure is
      positively associated with type 2 diabetes and high-grade prostate cancer. In
      addition, a natural experiment has suggested an association between overexposure
      to inorganic hexavalent selenium and two neurodegenerative diseases, amyotrophic
      lateral sclerosis and Parkinson's disease. Risk assessments should be revised to
      incorporate the results of studies demonstrating toxic effects of selenium.
      Additional observational studies and secondary analyses of completed randomized
      trials are needed to address the uncertainties regarding the health risks of
      selenium exposure.

PMID- 30280318
TI  - The folate receptor beta as a macrophage-mediated imaging and therapeutic target
      in rheumatoid arthritis.
AB  - Macrophages play a key role in the pathophysiology of rheumatoid arthritis (RA).
      Notably, positive correlations have been reported between synovial macrophage
      infiltration and disease activity as well as therapy outcome in RA patients.
      Hence, macrophages can serve as an important target for both imaging disease
      activity and drug delivery in RA. Folate receptor beta (FRbeta) is a
      glycosylphosphatidyl (GPI)-anchored plasma membrane protein being expressed on
      myeloid cells and activated macrophages. FRbeta harbors a nanomolar binding
      affinity for folic acid allowing this receptor to be exploited for RA disease
      imaging (e.g., folate-conjugated PET tracers) and therapeutic targeting (e.g.,
      folate antagonists and folate-conjugated drugs). This review provides an overview
      of these emerging applications in RA by summarizing and discussing properties of
      FRbeta, expression of FRbeta in relation to macrophage polarization, FRbeta
      targeted in vivo imaging modalities, and FRbeta-directed drug targeting.

PMID- 30280319
TI  - The Development and Validation of a Workplace-Based Leadership Program for Senior
      Residents in Psychiatry.

PMID- 30280320
TI  - Changes in automated external defibrillator use and survival after out-of
      hospital cardiac arrest in the Nijmegen area.
AB  - PURPOSE: Out-of-hospital cardiac arrests (OHCAs) are a major healthcare problem.
      Over the years, several initiatives have contributed to more lay volunteers
      providing cardiopulmonary resuscitation (CPR) and increased use of automated
      external defibrillators (AEDs) in the Netherlands. As part of a quality and
      outcomes program, we registered bystander CPR, AED use and outcome in the
      Nijmegen area. METHODS: Prospective resuscitation registry with a study cohort of
      non-traumatic OHCA cases from 2013-2016 and historical controls from 2008-2011.
      In line with previous reports, we studied patients transported to the hospital
      (Radboudumc, Nijmegen, the Netherlands) and excluded arrests witnessed by the
      emergency medical service (EMS). Primary outcomes were return of spontaneous
      circulation (ROSC) and survival to discharge. RESULTS: In the study cohort (n =
      349) the AED was attached more often than in the historical cohort (n = 180): 46%
      vs. 23% and the proportion of bystander CPR was higher: 78% vs. 63% (both p <
      0.001). A higher proportion of patients received an AED shock (39% vs. 15%, p <
      0.001) and the number of required shocks by the EMS was lower (2 vs. 4, p =
      0.004). Survival to discharge was higher (47% vs. 33%, p = 0.002) without
      differences in ROSC. The survival benefit was restricted to patients with a
      shockable initial rhythm. In both cohorts, bystander CPR and AED use were
      independently associated with survival. CONCLUSION: In patients admitted after
      OHCA, survival to discharge has markedly improved to 40-50%, comparable with
      other Dutch registries. As increased bystander CPR and the doubled use of AEDs
      seem to have contributed, all civilian-based resuscitation initiatives should be
      encouraged.

PMID- 30280321
TI  - Leptoceridae (Insecta, Trichoptera) from Serra da Canastra Mountain Range,
      Southeast Brazil: Diversity, Distribution, and Description of Two New Species.
AB  - The Brazilian savanna, also known as Cerrado, is one of the world's biodiversity
      hotspots, covering about 22% of the country. Nevertheless, this region has been
      suffering an accelerated process of degradation due to the agribusiness
      expansion. This study contributes to increasing knowledge on the Leptoceridae
      fauna of the Serra da Canastra Mountains at the Minas Gerais State, Brazil.
      Herein, we illustrate and describe two new species of Leptoceridae, Notalina
      franciscana sp. nov. and Oecetis catagua sp. nov., and provide additional data on
      the richness and distribution of Leptoceridae species in the Parque Nacional da
      Serra da Canastra and surrounding areas. Furthermore, ten species are firstly
      recorded from Minas Gerais State, increasing the number of Leptoceridae species
      recorded in the state from 30 to 42.

PMID- 30280323
TI  - [Lung cancer under stress].
AB  - BACKGROUND: Autophagy is a cellular mechanism involved in maintaining cellular
      homeostasis and warranting cellular survival under stress, and may be
      therapeutically exploited. Autophagy assessment in vitro is well established, but
      analysis in formalin-fixed and paraffin-embedded (FFPE) tissue is still poorly
      standardized. Expression analysis of autophagy-associated markers in diagnostic
      FFPE tissue aids in translating in vitro findings to the clinic and may
      contribute to a future quest for predictive markers. MATERIAL AND METHODS: We
      have established a reliable visualization of autophagy-related proteins in FFPE
      tissue by immunohistochemistry, using lung cancer cell lines with functionally
      modified autophagy states and marker-depletion, respectively, and evaluated the
      prognostic impact of autophagy-related markers in lung cancer patients. RESULTS:
      Dot-like staining was observed for LC3 and p62, representing the degrading
      autophagic vesicles. Stainings correlated significantly with quantitative protein
      expression assessed by western blot in cell lines and FFPE tumor tissue. In stage
      I/II non-small cell lung cancer cases and a large cohort of pulmonary squamous
      cell carcinomas, dot-like LC3 and p62 staining lacked clear prognostic value, but
      p62 expression was an independent prognostic factor for shorter survival in both
      cohorts and using internal validation models. CONCLUSIONS: Valid visualization of
      autophagy-related markers in FFPE tissue is feasible. We could not demonstrate a
      clear prognostic role of autophagy status as deducted from LC3-p62 co-expression.
      The autophagy independent role of p62 in lung cancer warrants further
      investigation, as well as crosstalk with other stress factors or the role of
      autophagy induction during or after treatment.

PMID- 30280322
TI  - Interactions of cantharidin-like inhibitors with human protein phosphatase-5 in a
      Mg2+ system: molecular dynamics and quantum calculations.
AB  - The serine/threonine protein phosphatase type 5 (PP5) is a promising target for
      designing new antitumor drugs. This enzyme is a member of the PPP phosphatases
      gene family, which catalyzes a dephosphorylation reaction: a regulatory process
      in the signal transduction pathway that controls various biological processes.
      The aim of this work is to study and compare the inhibition of PP5 by ten
      cantharidin-like inhibitors in order to bring about contributions relevant to the
      better comprehension of their inhibitory activity. In this theoretical
      investigation, we used molecular dynamics techniques to understand the role of
      key interactions that occur in the protein active site; QM calculations were
      employed to study the interaction mode of these inhibitors in the enzyme. In
      addition, atoms in molecules (AIM) calculations were carried out to characterize
      the chemical bonds among the atoms involved and investigate the orbital
      interactions with their respective energy values. The obtained results suggest
      that the Arg275, Asn303, His304, His352, Arg400, His427, Glu428, Val429, Tyr451,
      and Phe446 residues favorably contribute to the interactions between inhibitors
      and PP5. However, the Asp271 and Asp244 amino acid residues do not favor such
      interactions for some inhibitors. Through the QM calculations, we can suggest
      that the reactional energy of the coordination mechanism of these inhibitors in
      the PP5 active site is quite important and is responsible for the inhibitory
      activity. The AIM technique employed in this work was essential to get a better
      comprehension of the transition states acquired from the mechanism simulation.
      This work offers insights of how cantharidin-like inhibitors interact with human
      PP5, potentially allowing the design of more specific and even less cytotoxic
      drugs for cancer treatments. Graphical Abstract Interactions of cantharidin-like
      inhibitors with human protein phosphatase-5 in a Mg2+ system.

PMID- 30280325
TI  - Microflora of normal maxillary sinuses: does it justify perioperative antibiotic
      treatment in sinus augmentation procedures.
AB  - OBJECTIVES: To investigate bacterial flora of normal maxillary sinuses in order
      to facilitate perioperative antibiotic management in sinus augmentation
      procedures. MATERIALS AND METHODS: Specimens of maxillary sinus mucosa were
      harvested during planned orthognatic surgery in 18 patients with no evidence of
      rhinosinusitis. The samples were processed according to hospital routine for
      aerobic and anaerobic cultures. RESULTS: Ten maxillary sinuses were found
      sterile. Twenty-six (72%) maxillary mucosa specimens were culture-positive.
      Aerobes were recovered in 21 sinus samples (58%), predominantly as polymicrobial
      flora (18 cultures, 50% of all specimens), S. aureus in 2 sinuses of the same
      patient (6% of the samples), and Bacillus sp. in 1 sinus (3%). Anaerobes were
      isolated in 20 of 26 culture-positive specimens (56% of all sinus samples). They
      were recovered alone in 5 samples. Fifteen anaerobic cultures were polymicrobial
      (42% of all samples). Propionibacterium acnes was isolated from another 5 sinuses
      (14%) of 3 patients. CONCLUSIONS: Our data support the policy of perioperative
      antibiotic prophylaxis in sinus augmentation procedures where Schneiderian
      membrane is perforated. CLINICAL RELEVANCE: Evaluating the need of a
      perioperative antibiotic therapy in sinus augmentation procedures.

PMID- 30280324
TI  - Evaluation of the genotoxic potential of different delivery methods of at-home
      bleaching gels: a single-blind, randomized clinical trial.
AB  - OBJECTIVE: This single-blind, parallel, randomized clinical trial evaluated the
      genotoxic potential and effectiveness of 10% hydrogen peroxide (HP) in patients
      submitted to at-home bleaching. MATERIALS AND METHODS: Sixty young volunteers
      with maxillary incisors equal to or darker than M1.5 were included in the study.
      Patients were submitted to bleaching for 14 days (30 min/day) with one of the
      three 10% HP treatments: the bleaching agent was delivered in a bleaching tray
      (White Class, FGM), whitening strips (White Strips, Oral-b), or in prefilled
      disposable trays (Opalescence Go, Ultradent). The color change was evaluated with
      the Vita Bleachedguide, and the micronucleus test of exfoliative oral mucosa was
      carried out, starting from a count of 1000 cells, at the baseline, immediately
      after and 30 days after the end of the treatment. The micronucleus data were
      evaluated with the Kruskal-Wallis and Wilcoxon tests and color change with the
      two-way ANOVA test and the Tukey test (alpha = 0.05). RESULTS: Significant
      whitening was observed for all groups after 14 days (p = 0.001) and was
      maintained after 30 days, with no difference between groups (p = 0.42). The
      micronucleus count did not indicate genotoxic potential in any of the groups
      studied (p = 0.32), irrespective of the time intervals (p = 0.62). CONCLUSION: No
      genotoxic effects of 10% HP were observed in patients submitted to at-home
      bleaching systems (30 min/day for 14 days), even 30 days after the end of
      treatment. CLINICAL SIGNIFICANCE: It is safe to use different systems to deliver
      10% HP during at-home bleaching according to the manufacturers' recommendations,
      with no risk of genotoxic effects applied.

PMID- 30280326
TI  - Influence of different thickeners in at-home tooth bleaching: a randomized
      clinical trial study.
AB  - OBJECTIVES: To evaluate the effects of 10% carbamide peroxide (CP) with two
      different thickeners, carbopol (CPc) and natrosol (CPn), on color variation (CV),
      tooth sensitivity (TS), and cytotoxicity (CC). METHODS: Seventy subjects were
      distributed into the CPc or CPn groups (n = 35), in a parallel group, randomized,
      controlled, single-blind clinical trial. Bleaching gels were used by volunteers
      for 4 h daily for 2 weeks. Color evaluation was performed using a reflectance
      spectrophotometer, before bleaching treatment (BT), immediately after the first
      and second weeks of BT, and 1 week and 1 month after BT ended. TS was evaluated
      using two pain scales, before, during, and after BT. CC was evaluated using MTT
      after exposure of MDPC-23 cells to the bleaching gels for 4 h. Epoxy replicas of
      the subjects teeth were made before and after BT and analyzed using a scanning
      electronic microscope. The data was analyzed using statistical methods. RESULTS:
      CV and TS showed similar variation between both bleaching gels (p <= 0.05). None
      of the protocols affected cellular metabolism or the surface morphology of
      enamel. CONCLUSIONS: Bleaching gels with carbopol and natrosol as thickening
      agents produced similarly effective tooth bleaching and TS, but did not cause
      cytotoxicity. CLINICAL RELEVANCE: Natrosol could be an alternative as a thickener
      used in bleaching gels due to its similar bleaching effect and TS when compared
      with Carbopol.

PMID- 30280328
TI  - Combined effects of new complete denture fabrication and simplified dietary
      advice on nutrient intake in edentulous elderly patients for 6 months.
AB  - OBJECTIVE: The aim was to evaluate the combined effects of a new complete denture
      fabrication and simple dietary advice (using unique pamphlets) by dentists on
      nutrient intake in edentulous elderly patients. MATERIALS AND METHODS: A
      randomized controlled trial was performed on edentulous elderly patients who were
      randomly allocated to either an intervention or a control group. The intervention
      group received a new complete denture and simple dietary advice, whereas the
      control group received a new complete denture and denture care advice. The
      outcomes of this trial (nutrient intakes) were calculated using a brief-type self
      administered diet history questionnaire (BDHQ) and assessed at three time points
      (pretreatment and 3 and 6 months post-treatment). RESULTS: At 3 months post
      treatment, the intake of several nutrients such as proteins (p = 0.004),
      magnesium (p < 0.001), and vitamin B1 (p = 0.014) was significantly higher in the
      intervention group than the control group, whereas at 6 months post-treatment,
      plant protein (p = 0.028) intake was significantly higher in the intervention
      group than the control group. On the contrary, animal protein (p = 0.049) and
      vitamin B12 (p = 0.028) intakes were significantly higher in the control group.
      CONCLUSIONS: New complete denture fabrication with simple dietary advice might
      improve nutrient intake in elderly edentulous patients; however, the effect is
      probably short term. CLINICAL SIGNIFICANCE: New complete denture fabrication
      along with simple dietary advice by dentists might improve nutrient intake in
      edentulous elderly patients. Therefore, regular use of these interventions in the
      dental setting might have long-term effects on nutrient intake in elderly
      edentulous patients. TRIAL REGISTRATION: UMIN-CTR Clinical Trial, unique trial
      number: UMIN000017879.

PMID- 30280327
TI  - The effect of age, gender, and time between blood draw and start of
      centrifugation on the size outcomes of platelet-rich fibrin (PRF) membranes.
AB  - OBJECTIVES: Platelet-rich fibrin (PRF) has been utilized in regenerative
      dentistry as a supra-physiological concentrate of autologous growth factors
      capable of stimulating tissue regeneration. Due to the variability in the
      macroscopic morphology/size of PRF membranes observed between patients, we were
      interested in studying the effects of patient age, gender, and time between blood
      draw and the start of centrifugation on the size outcomes of PRF membranes.
      Despite PRF therapy being increasingly more popular in private practice, to date,
      no study has investigated the effects of the delay between blood draw and the
      start of centrifugation in a clinical setting. MATERIALS AND METHODS: A total of
      60 patients enrolled in this study were divided into 6 groups of 10 patients
      each, including male and female patients categorized into age groups 21-40, 41
      60, and 61-80 years. From each patient, a total of five PRF membranes were
      fabricated from 10-mL tubes following centrifugation starting after 0, 30, 60,
      90, and 120 s. In total, 300 PRF membranes were produced in this study to
      investigate the effects of patient age, gender, and time on the size outcomes of
      PRF membranes. RESULTS: A longer delay by the clinician before starting
      centrifugation following blood draw led to a smaller final size of PRF membranes.
      At 90 s following blood draw, a significant (13%) reduction in PRF membrane size
      was observed. After 120 s, a significant (23%) reduction was observed.
      Additionally, female patients had on average 17% larger membranes compared to men
      (p < 0.05, 300 samples). Lastly, the size outcomes of the PRF membranes was
      largest in patients aged 61-80, followed by those aged 41-60 and 21-40. However,
      no statistically significant differences in PRF membrane sizes were reported
      between age groups. CONCLUSIONS: The time at which a centrifugation procedure
      begins following blood draw is critical to optimize the size outcomes of PRF
      membranes. In general, approximately 15 s is required per tube to harvest 9-10 cc
      of blood. Therefore, a 60- to 90-s interval between blood draw and the start of
      centrifugation should be a parameter that is respected by clinicians to avoid
      significant changes in the macroscopic morphology/size of fabricated PRF
      membranes. Furthermore, females and older patients produced larger membranes,
      likely due to lower red blood cell counts derived from their peripheral blood.
      CLINICAL RELEVANCE: The findings from the present study demonstrate that on
      average, a clinician has approximately 60-90 s between blood draw and the start
      of the centrifugation cycle to produce standard-sized PRF membranes. Shortly
      thereafter, a significant reduction in size is observed. Additionally, females
      and older patients were found to produce larger PRF membranes. Centrifugation
      protocols may therefore be adapted accordingly.

PMID- 30280330
TI  - Multiregional viscoelastic characterization of the corona radiata in the sagittal
      plane of the porcine brain.
AB  - Detailed finite element (FE) models are used as promising tools to investigate
      traumatic brain injuries, although their accuracy is strongly dependent on the
      characterization of the mechanical behaviors of the different anatomic structures
      in the brain. In some cases, when the FE models require finer spatial resolution,
      the heterogeneous and anisotropic corona radiata cannot be taken as a homogeneous
      whole body. In this work, indentation experiments were conducted on the anterior,
      superior, and posterior regions of the corona radiata in the sagittal plane. To
      determine the parameters available for computational modeling purposes, a linear
      viscoelastic model using the Boltzmann hereditary integral was fitted to the
      force-time data of the three regions. In the indentation tests, the superior
      region appeared to be the stiffest, while no significant differences were
      observed between the anterior and posterior regions until the viscoelastic tissue
      reached equilibrium. During the period of relaxation, statistical comparisons
      among the different regions indicated significant differences between the
      superior and anterior regions, and between the superior and posterior regions.
      This work complements existing investigations into the anatomic heterogeneity of
      the brain, and contributes toward improving the spatial resolution of future
      computational models. Graphical abstract Relaxation functions of different
      regions based on the Prony series parameters and the multiregional Kolmogorov
      Smirnov comparisons (*p < 0.017). The anisotropy and interregional differences of
      the corona radiata observed in this study are supplementary to the previous
      explorations of the mechanical properties of different brain anatomic structures.

PMID- 30280329
TI  - Mitigation of Oxidation in Therapeutic Antibody Formulations: a Biochemical
      Efficacy and Safety Evaluation of N-Acetyl-Tryptophan and L-Methionine.
AB  - PURPOSE: Biotherapeutics can be susceptible to oxidation during manufacturing and
      storage. Free L-methionine is known to protect methionine residues in proteins
      from oxidation. Similarly, free tryptophan and other indole derivatives have been
      shown to protect tryptophan residues from oxidation. N-acetyl-DL-tryptophan was
      previously identified as a potentially superior antioxidant to tryptophan as it
      has a lower oxidation potential and produces less peroxide upon light exposure.
      This study sought to confirm the antioxidant efficacy and safety of N-acetyl-DL
      tryptophan and L-methionine as formulation components for biotherapeutic drugs.
      METHODS: Antibodies were subjected to AAPH and light exposure in the presence of
      N-acetyl-DL-tryptophan and L-methionine. Oxidation in relevant CDR and Fc
      residues was quantified by peptide map. In silico, in vitro, and in vivo studies
      were performed to evaluate the safety of N-acetyl-DL-tryptophan and L-methionine.
      RESULTS: Peptide mapping demonstrated that N-acetyl-DL-tryptophan was effective
      at protecting tryptophans from AAPH stress, and that the combination of N-acetyl
      DL-tryptophan and L-methionine protected both tryptophan and methionine from AAPH
      stress. The safety assessment suggested an acceptable safety profile for both
      excipients. CONCLUSIONS: N-acetyl-tryptophan and L-methionine effectively reduce
      the oxidation of susceptible tryptophan and methionine residues in antibodies and
      are safe for use in parenteral biotherapeutic formulations.

PMID- 30280331
TI  - Head-mounted interface for intuitive vision control and continuous surgical
      operation in a surgical robot system.
AB  - Although robot-assisted surgeries offer various advantages, the discontinuous
      surgical operation flow resulting from switching the control between the patient
      side manipulators and the endoscopic robot arm can be improved to enhance the
      efficiency further. Therefore, in this study, a head-mounted master interface
      (HMI) that can be implemented to an existing surgical robot system and allows
      continuous surgical operation flow using the head motion is proposed. The
      proposed system includes an HMI, a four degrees of freedom endoscope control
      system, a simple three-dimensional endoscope, and a da Vinci Research Kit. Eight
      volunteers performed seven head movements and their data from HMI was collected
      to perform support vector machine (SVM) classification. Further, ten-fold cross
      validation was performed to optimize its parameters. Using the ten-fold cross
      validation result, the SVM classifier with the Gaussian kernel (sigma = 0.85) was
      chosen, which had an accuracy of 92.28%. An endoscopic control algorithm was
      developed using the SVM classification result. A peg transfer task was conducted
      to check the time-related effect of HMI's usability on the system, and the paired
      t test result showed that the task completion time was reduced. Further, the time
      delay of the system was measured to be 0.72 s. Graphical abstract A head-mounted
      master interface (HMI), which can be implemented to an existing surgical robot
      system, was developed to allow simultaneous surgical operation flow. The
      surgeon's head motion is detected through the proposed HMI and classified using a
      support vector machine to manipulate the endoscopic robotic arm. A classification
      accuracy of 92.28% was achieved.

PMID- 30280332
TI  - Does Sleeve Gastrectomy Cause Barrett's Oesophagus?

PMID- 30280333
TI  - Gastric Banding: Complications Identified by CT.
AB  - PURPOSE: Laparoscopic adjustable gastric banding (LAGB) used to be a common
      procedure at the turn of the century and is still frequently encountered on CT
      scans in common clinical practice. Our aim is to present the frequency and
      spectrum of complication associated with LAGB, as observed in CT. MATERIALS AND
      METHODS: After approval of our institutional review board, a retrospective search
      for LAGB in CT interpretations using the term "band" between December 2011 and
      April 2017 was conducted. CT scans were reviewed to identify complications. The
      findings were divided into two groups: symptomatic, in which the complications
      caused acute symptoms for which CT scans were conducted, and incidental, in which
      complications were incidentally identified. The frequency of complications was
      calculated. RESULTS: We identified 160 patients who underwent LAGB and performed
      a CT scan. Complications were identified in 69/160 (43.1%) patients, with a total
      of 83 findings: 47/160 (29.4%) esophageal dilatation, 13/160 (8.2%) pulmonary
      complications, 6/160 (3.8%) abdominal abscesses, 5/160 (3.1%) small bowel
      obstructions, 4/160 (2.5%) intragastric band erosions, 4/160 (2.5%) tube
      disconnections, 3/160 (1.9%) port site and tube course infections, and 1/160
      (0.6%) small pouch bezoars. When compared with patients' referral notes, 38/83
      (45.8%) of the findings were associated with acute symptoms, whereas 45/83
      (54.2%) of the findings were incidental. Eighteen percent of the incidental
      complications were clinically important. CONCLUSION: Complications were found in
      43% of CT scans of patients who underwent LAGB; less than half of the findings
      were symptomatic. Some of the incidentally identified complications had
      substantial clinical importance.

PMID- 30280334
TI  - Characterization of pyrolysis bio-oil derived from intermediate pyrolysis of
      Aegle marmelos de-oiled cake: study on performance and emission characteristics
      of C.I. engine fueled with Aegle marmelos pyrolysis oil-blends.
AB  - The present research focuses on the analyzing the characteristics of bio-oil
      derived from intermediate pyrolysis of Aegle marmelos (AM) seed cake and its
      suitability for C.I. engine adaptation. Owing to the high volatile matter content
      of 73.69%, Aegle marmelos biomass was selected as the feedstock for this
      research. The intermediate pyrolysis was carried out at 600  degrees C in a 2-kg
      fixed bed type pyrolysis reactor at a heating rate of 10  degrees C/min and the
      obtained bio-oil was characterized by different analytical methods. As per
      American Society for Testing and Materials (ASTM) standards, physicochemical
      properties of the bio-oil were tested and it was observed that bio-oil is a
      highly viscous fluid with low calorific value. Analysis of bio-oil through FT-IR
      and GC-MS examination confirmed the presence of phenol, esters, alkyl, and
      oxygenated compounds. The performance and emission testing of direct injection
      diesel engine were conducted with various bio-oil blends and the results were
      compared with baseline diesel fuel. The experimental results showed that the
      addition of bio-oil decreased BTE (%) while increasing the BSEC (MJ/kW-h). At the
      same time, increasing the bio-oil ratio with diesel decreases dangerous emissions
      such as carbon monoxide and oxides of nitrogen emissions in the engine exhaust.
      According to engine test result, it was suggested that up to 20% of AM bio-oil
      (F20) can be employed as engine fuel for better engine operating characteristics.

PMID- 30280335
TI  - Accumulation of heavy metals in native Andean plants: potential tools for soil
      phytoremediation in Ancash (Peru).
AB  - Metal contamination is a recurring problem in Peru, caused mainly by mine
      tailings from a past active mining activity. The Ancash region has the largest
      number of environmental liabilities, which mobilizes high levels of metals and
      acid drainages into soils and freshwater sources, posing a standing risk on human
      and environmental health. Native plant species spontaneously growing on naturally
      acidified soils and acid mine tailings show a unique tolerance to high metal
      concentrations and are thus potential candidates for soil phytoremediation.
      However, little is known about their propagation capacity and metal accumulation
      under controlled conditions. In this study, we aimed at characterizing nine
      native plant species, previously identified as potential hyperaccumulators, from
      areas impacted by mine tailings in the Ancash region. Plants were grown on mine
      soils under greenhouse conditions during 5 months, after which the concentration
      of Cd, Cu, Ni, Pb, and Zn was analyzed in roots, shoots, and soils. The
      bioaccumulation (BAF) and translocation factor (TF) were calculated to determine
      the amount of each metal accumulated in the roots and shoots and to identify
      which species could be better suited for phytoremediation purposes. Soil samples
      contained high Cd (6.50-49.80 mg/kg), Cu (159.50-1187.00 mg/kg), Ni (3.50-8.70
      mg/kg), Pb (1707.00-4243.00 mg/kg), and Zn (909.00-7100.00 mg/kg) concentrations
      exceeding national environmental quality standards. After exposure to mine
      tailings, concentrations of metals in shoots were highest in Werneria nubigena
      (Cd, 16.68 mg/kg; Cu, 41.36 mg/kg; Ni, 26.85 mg/kg; Zn, 1691.03 mg/kg),
      Pennisetum clandestinum (Pb, 236.86 mg/kg), and Medicago lupulina (Zn, 1078.10
      mg/kg). Metal concentrations in the roots were highest in Juncus bufonius (Cd,
      34.34 mg/kg; Cu, 251.07 mg/kg; Ni, 6.60 mg/kg; Pb, 718.44 mg/kg) and M. lupulina
      (Zn, 2415.73 mg/kg). The greatest BAF was calculated for W. nubigena (Cd, 1.92;
      Cu, 1.20; Ni, 6.50; Zn, 3.50) and J. bufonius (Ni, 3.02; Zn, 1.30); BCF for
      Calamagrostis recta (Cd, 1.09; Cu, 1.80; Ni, 1.09), J. bufonius (Cd, 3.91; Cu,
      1.79; Ni, 18.36), and Achyrocline alata (Ni, 137; Zn, 1.85); and TF for W.
      nubigena (Cd, 2.36; Cu, 1.70; Ni, 2.42; Pb, 1.17; Zn, 1.43), A. alata (Cd, 1.14;
      Pb, 1.94), J. bufonius (Ni, 2.72; Zn, 1.63), and P. clandestinum (Zn, 1.14). Our
      results suggest that these plant species have a great potential for soil
      phytoremediation, given their capability to accumulate and transfer metals and
      their tolerance to highly metal-polluted environments in the Andean region.

PMID- 30280336
TI  - Metals in a northern Nile Delta lake: water, suspended particulates, sediments,
      and biota.
AB  - Lake Edku is one of the important fishing areas in the Nile Delta. It is exposed
      to different quantities of serious pollutants in particular metals. To overall
      appraise the risk and status of metals in the lake, a comprehensive study of
      total concentrations of cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe),
      manganese (Mn), nickel (Ni), and zinc (Zn) in sediments and spatial-temporal
      variations of these metals in the dissolved and suspended particulates, and some
      tissues of Tilapias niloticus, was conducted from ten sampling sites during 2016.
      Results showed that none of the investigated metals exceeded the limits
      considered as hazardous for aquatic life in water. The highest concentrations of
      Cd, Cu, Ni, and Zn were observed in suspended particulate matter, which may
      precipitate on the surface of the sediments. Potential ecological risk analysis
      of the majority of the investigated metals in the sediment indicated that Lake
      Edku posed a low ecological risk. The estimated values of all metals in tissues
      of Tilapia niloticus were below the international permissible limits. Moreover,
      the potential risk of metals to human via the consumption of Tilapia niloticus
      was estimated using the weekly intake levels, which was lower than the WHO's safe
      provisional tolerant weekly intake levels. These results prove the importance of
      performing measurements of contaminants in various compartments of Lake Ecosystem
      including sediment, biota, and suspended particulate matter for proper
      management.

PMID- 30280337
TI  - Performance of full-scale coagulation-flocculation/DAF as a pre-treatment
      technology for biodegradability enhancement of high strength wastepaper-recycling
      wastewater.
AB  - Paper mill wastewater leads to a serious damage on the environment owing to the
      high content of organic matters, suspended solids, toxic substances, and lignin.
      Hence, exploring new treatment technologies is the passion of environmental
      engineers to minimize the effluent impact on the environment and cleaner
      production aspects. This research focused on the performance of full-scale
      coagulation-fluctuation/DAF system for pre-treatment of high strength wastepaper
      recycling wastewater and its effect on biodegradability improvement. To optimize
      unit performance, optimum coagulant and flocculant doses were firstly determined
      by jar test without prior change and adjustment of pH in lab-scale experiments.
      The optimum dosages were obtained by 1500 mg L-1 polyaluminum chloride (PACl) as
      coagulant coupled with 40 mg L-1 cationic polyacrylamide (C-PAM) as flocculant.
      Percentage removals of 39 +/- 10, 6.8 +/- 3.6, 31.0 +/- 6.7, 24.0 +/- 3.8, and
      33.0 +/- 20.0 were achieved for COD, sCOD, BOD5, sBOD5, and color, respectively.
      The average BOD5 to COD ratio after pre-treatment increased from 0.44 to 0.5,
      whereas the ratio of sBOD5/sCOD dropped from 0.65 to 0.53. A superior
      effectiveness in reduction of TSS (98.1%) and VSS (98.4%) was also achieved. The
      results show that the application process is able to prevent malfunction
      operation in the following bioreactors which is obtainable through bio
      treatability enhancement of pre-treated wastewater and reducing the risks of
      clogging and sludge washout. Attached growth processes are suggested to be
      applied in the further anaerobic/aerobic processes because of high proportion of
      soluble fraction of COD in the effluent to avoid poor floc formation and
      dispersed growth problems.

PMID- 30280338
TI  - An empirical model for the evaluation of the dissolution rate from a DNAPL
      contaminated area.
AB  - This paper investigates dynamic variation in the morphologic distribution of
      dense non-aqueous phase liquids (DNAPLs), which take into account the coupled
      mass transfer. Experiments were carried out in a 2D tank representing a
      reconstructed aquifer model. DNAPL dissolution rates were investigated over a
      wide range of DNAPL saturations, several source configurations, and different
      hydraulic conditions. Morphometric indexes are presented that take into
      consideration further factors affecting the dissolution process. Local
      information regarding transport parameters related to the characteristics of the
      medium was obtained through a neural network and an optimization algorithm
      applied to experimental tracer tests. The history of DNAPL source architecture,
      in terms of saturation, indentation grade, and orientation, was determined by
      image analysis. Dissolved concentrations were registered and mass transfer rate
      coefficients were obtained for a wide range of source-zone configurations. A
      statistical analysis was performed to develop a constitutive equation that is
      descriptive of the mass transfer rate as a function of source-zone metric
      characteristics. A new empirical dissolution model using the proposed
      morphometric parameters is presented and compared with other models. The mass
      transfer correlation reported incorporates morphometric parameters and considers
      the complex and variable architecture of non-miscible contaminants. The proposed
      correlation can be used for an initial assessment of non-aqueous phase liquid
      (NAPL) dissolution rates over a wide range of saturation (residual and non
      residual) conditions and different aqueous phase velocities within the NAPL
      source zone.

PMID- 30280339
TI  - Pesticide residues in Indian raw honeys, an indicator of environmental pollution.
AB  - Honey has multifaceted beneficial properties, but polluted environment and
      unapproved apicultural practices have led to its contamination. In this study,
      QuEChERS method followed by chromatographic analysis by GC-MUECD/FTD and GC-MS
      was validated and used for determination of 24 pesticides in 100 raw honey
      samples from various floral origins of Northern India. Matrix-matched
      calibrations showed that the method was selective and linear (r2 > 0.99) with
      detection limit < 9.1 ng g-1 for all the studied pesticides except for
      monocrotophos (21.3 ng g-1). The average recoveries at different fortification
      levels ranged from 86.0 to 107.7% with relative standard deviation < 20%.
      Pesticide residues were detected in 19.0% samples, and most prevalent compounds
      detected were dichlorvos in 6.0% samples followed by monocrotophos (5.0%),
      profenofos (5.0%), permethrin (4.0%), ethion (3.0%), and lindane (3.0%) with
      concentrations ranging from 58.8 to 225.5, from 96.0 to 430.1, from 14.6 to 43.2,
      from 27.8 to 39.6, from 25.6 to 28.0, and from 19.6 to 99.2 ng g-1, respectively.
      Honey samples originating from cotton, sunflower, and mustard crops (33.3%) that
      tested positive for pesticide residues were found to be significantly higher (p <
      0.05) than the honey originating from natural and fruity vegetation (13.5%).
      Therefore, considering the contamination of environmental compartments due to
      extensive application of pesticides in the study area and their potential for
      subsequent transfer to honey by the expeditious bees, the results of present
      study proclaim that honey may be used as an indicator of environmental pollution.
      Further, estimated daily intakes of all contaminants were found to be at levels
      well below their acceptable daily intakes suggesting that consumption of honeys
      at current levels does not pose deleterious effects on human health. However,
      precautionary measures should always be taken considering the customary honey
      feeding in infants and cumulative effect of these chemicals in the foreseeable
      future.

PMID- 30280340
TI  - Versatility of iron-rich steel waste for the removal of high arsenic and sulfate
      concentrations in water.
AB  - The aim of this work is to evaluate the application of a steel waste, basic
      oxygen furnace sludge (BOFS), rich in iron, to treat water contaminated with
      elevated arsenic and sulfate concentrations. In the first step, three doses (10,
      60, and 80 g L-1) of BOFS were tested to investigate the removal of As(III) and
      As(V) (67 mg L-1) and sulfate (3700 mg L-1) separately from an aqueous solution.
      In the second step, the efficacies of BOFS (10 g L-1) and commercial ZVI (5 g L
      1) were compared to simultaneously remove arsenic and sulfate. The pH of the feed
      solution was adjusted to 2.5 and monitored during the experiment. The use of BOFS
      achieved arsenic removal up to 92% and sulfate removal of nearly 40% after 72 h
      of contact time. Use of BOFS also increased the solution pH to 12. Similar
      removal levels were achieved with both BOFS and ZVI. These results confirm the
      potential application of BOFS to remove high arsenic and sulfate concentrations
      from acidic solutions. The data obtained here should be used as a basis for
      further studies on the remediation of acid mine drainage with high concentrations
      of arsenic and sulfate using an abundant and low-cost steel waste.

PMID- 30280341
TI  - Efficient water decontamination using layered double hydroxide beads
      nanocomposites.
AB  - Ni-Al-CO3-layered double hydroxide (LDH) with Ni:Al ratio (3:1) and their
      nanocomposites with alginate and chitosan beads were prepared and examined for
      their efficiency in removal of Cd2+ and Cu2+ ions from wastewater. Different
      parameters such as contact time, pH value, adsorbent weight, and heavy metal ion
      concentration on the removal efficiency were examined and reported. The prepared
      beads were examined using X-ray diffraction (XRD), TEM, SEM, and FTIR. Our
      results revealed a successful preparation of the LDH in rhombohedral hexognal
      crystal form and the alginate-LDH-chitosan beads. The optimized batch experiment
      conditions in ambient room temperature were found to be 2 g/L adsorbent dose, 50
      mg/L initial concentration of meal, contact time of 2 h, and pH ~ 5 and 6 for
      removal of Cu2+ and Cd2+, respectively. The adsorption process was well fitted
      with Langmuir and Freundlich isotherm models (higher R2), with trivial advantage
      for Freundlich approach. Kinetic studies showed that the adsorption of both Cd2+
      and Cu2+ followed the pseudo-second-order. The current study demonstrated that
      the Ni-Al-CO3 LDH and their novel alginate-chitosan-based nanocomposite could be
      further tailored and used as efficient adsorbents for the uptake of heavy metals
      from wastewater.

PMID- 30280342
TI  - Effects of site-specific climatic conditions on the radial growth of the lichen
      biomonitor Xanthoria parietina.
AB  - The protocols commonly applied in surveys with lichens as biomonitors of airborne
      trace elements require analyses of samples derived from thalli or parts of thalli
      grown in the last year before sampling, under the postulation that samples of the
      same size are of the same age. Unfortunately, the influence of ecological site
      specific factors on lichen growth is still largely ignored, so that samples of
      the same size collected in environmentally and climatically diverse sites might
      actually differ in age. This work aims at quantifying the influence of climatic
      conditions on the radial growth rates (RaGRs) of Xanthoria parietina, one of the
      most popular lichen biomonitors. RaGR was monitored in seven populations
      distributed along an altitudinal transect of 30 km in the Classical Karst (NE
      Italy), from 20 to 500 m above sea level. For c. 17 months, lobe growth was
      measured seasonally with a digital calliper, and site-specific climatic variables
      were monitored by means of thermo-hygrometric sensors and implemented by
      meteorological data. Finally, the lobe growth of X. parietina was modelled as a
      function of 18 environmental variables. Results revealed that thalli of
      relatively dry sites had significantly lower seasonal RaGR with respect to
      moister ones. Considering that cumulative precipitations were equally distributed
      along the transect, it was concluded that RaGR of X. parietina is affected
      negatively by high air temperatures and positively by high relative humidity. The
      importance of RaGR variation in lichen bioaccumulation studies is critically
      discussed.

PMID- 30280343
TI  - Biomechanical response of a submerged, rosette-forming macrophyte to wave action
      in a eutrophic lake on the Yungui Plateau, China.
AB  - Few studies have focused on the biomechanical responses of submerged, rosette
      forming macrophytes to wave action, water depth, or their co-occurrence in
      naturally eutrophic systems. The plant architecture, root anchorage strength
      related traits, leaf morphology, and biomechanics of Vallisneria natans
      inhabiting a range of water depths were examined along three transects (T1, T2,
      and T3) in a eutrophic lake, Lake Erhai, in Yunnan Province, China. These
      transects were exposed to weak wave action and hyper-eutrophication (T1),
      moderate wave action and eutrophication (T2), or strong wave action and
      eutrophication (T3). The results showed that V. natans was mainly distributed at
      intermediate depths, with the widest colonization depth in T1. The values of
      plant architecture, root anchorage strength-related traits, leaf morphology, and
      biomechanics were generally highest in T3 and smallest in T2. Along the depth
      gradient, these values were generally highest at 3.5, 2.5, and 2.5 m for the
      plants growing in T1, T2, and T3, respectively. These findings suggest that V.
      natans adopts a "tolerance" strategy to cope with the effects of strong wave
      action in eutrophic habitats and an "avoidance" strategy when exposed to moderate
      wave action in eutrophic areas. Since the absence of an avoidance strategy
      increases the resistance to low-light stress at the expense of increased drag
      forces, there is a limit to the wave action that V. natans can withstand. This
      study indicates that biomechanics could be important when determining the
      distribution pattern of V. natans in Lake Erhai.

PMID- 30280346
TI  - Sublethal effects of chronic exposure to CdO or PbO nanoparticles or their binary
      mixture on the honey bee (Apis millefera L.).
AB  - Cadmium and lead-based nanotechnologies are increasingly used in agricultural,
      industrial, and biological processes; however, potential adverse effects of
      nanomaterials on honey bees had not been assessed. In this study, effects of
      exposures to sublethal concentrations of PbO and CdO nanoparticles (NPs), either
      separately or in combination on honey bee (Apis mellifera) workers, were
      assessed. Honey bee workers were orally exposed for 9 days under laboratory
      conditions to sublethal concentrations (20% of LC50) of CdO (0.01 mg/ml-) and PbO
      (0.65 mg/ml-) NPs either separately or combined. Effects on survival, feeding
      rate, activity of acetylcholinesterase (AChE), and expression of selected stress
      related detoxifying enzymes were quantified. Survival and feeding rates decreased
      particularly in bees fed sugar syrup containing CdO NPs or binary mixtures of NPs
      of both metal oxides. Expressions of genes involved in detoxification of
      xenobiotics were affected by various combinations. Expression of catalase was
      13.6-fold greater in bees consumed sugar syrup diet containing binary mixture of
      sublethal concentrations of both CdO and PbO NPs than it was in unexposed,
      control bees. AChE activity in heads of honey bees was inhibited by 3.8-, 3.0-,
      and 2.8-fold relative to control, respectively, in response to exposure to Cd
      or/and Pb oxide NPs. This result indicates potential neurotoxic effects of these
      NPs to honey bees. CdO NPs exhibited greater potency to honey bees. Overall,
      sublethal concentrations of CdO or/and PbO NPs resulted in detrimental effects on
      honeybee workers.

PMID- 30280345
TI  - Competitive adsorption and desorption of arsenate, vanadate, and molybdate onto
      the low-cost adsorbent materials alum water treatment sludge and bauxite.
AB  - When low-cost adsorbents are being used to remove contaminant ions (e.g.
      arsenate, vanadate, and molybdate) from wastewater, competitive
      adsorption/desorption are central processes determining their removal efficiency.
      Competitive adsorption of As, V, and Mo was investigated using equimolar oxyanion
      concentrations in single, binary, and tertiary combinations in adsorption
      isotherm and pH envelope studies while desorption of previously adsorbed
      oxyanions was examined in solutions containing single and binary oxyanion
      combinations. The low-cost adsorbent materials used were alum water treatment
      sludge (amorphous hydroxy-Al) and bauxite ore (crystalline Al oxides). Adsorption
      isotherm and pH envelope studies showed that Mo had only a small effect in
      decreasing adsorption of As and V but V and As had substantial and similar
      effects in reducing adsorption of the other. As had a greater effect than V in
      reducing adsorption of Mo and it was concluded that the affinity of oxyanions for
      the surfaces of water treatment sludge and bauxite followed the order As > V >>
      Mo. In 0.3 M NaCl electrolyte, desorption of previously adsorbed oxyanions
      amounted to 0.3-3.4% for V and As, and 11-20% for Mo. As had approximately four
      times greater effect than Mo in increasing desorption of V while V had about
      three times the effect of Mo in increasing desorption of As. Thus, the order of
      oxyanions in inducing desorption of the other oxyanions (i.e. As on V and As) was
      the same as that for adsorption selectivity: As > V >> Mo. Water treatment sludge
      was a more effective adsorbent than bauxite because it had a greater adsorption
      capacity for all three anions and, in addition, they were held more strongly so
      desorption in the background electrolyte was proportionately less. It was
      concluded that at similar molar concentrations, arsenate would tend to reduce
      adsorption of vanadate as well as displace vanadate already held on adsorbent
      surfaces while both anions will compete effectively with molybdate. The limiting
      factor for simultaneous removal of As, V, and Mo from multielement solutions by
      adsorption will therefore be the removal of Mo.

PMID- 30280347
TI  - Assessment of elemental composition and properties of copper smelter-affected
      dust and its nano- and micron size fractions.
AB  - A comprehensive approach has been developed to the assessment of composition and
      properties of atmospherically deposited dust in the area affected by a copper
      smelter. The approach is based on the analysis of initial dust samples, dynamic
      leaching of water soluble fractions in a rotating coiled column (RCC) followed by
      the determination of recovered elements and characterization of size, morphology
      and elemental composition of nano-, submicron, and micron par ticles of dust
      separated using field-flow fractionation in a RCC. Three separated size fractions
      of dust (<0.2, 0.2-2, and >2 MUm) were characterized by static light scattering
      and scanning electron microscopy, whereupon the fractions were analyzed by ICP
      AES and ICP-MS (after digestion). It has been evaluated that toxic elements,
      which are characteristics for copper smelter emissions (As, Cu, Zn), are
      accumulated in fraction >2 MUm. At the same time, up to 2.4, 3.1, 8.2, 6.7 g/kg
      of As, Cu, Zn, Pb, correspondently, were found in nanoparticles (<0.2 MUm). It
      has been also shown that some trace elements (Sn, Sb, Ag, Bi, and Tl) are
      accumulated in fraction <0.2, and their content in this fraction may be one order
      of magnitude higher than that in the fraction >2 MUm, or the bulk sample. It may
      be assumed that Sn, Sb, Ag, Bi, Tl compounds are adsorbed onto the finest dust
      particles as compared to As, Cu, Zn compounds, which are directly emitted from
      the copper smelter as microparticles.

PMID- 30280344
TI  - Association of benzene exposure with insulin resistance, SOD, and MDA as markers
      of oxidative stress in children and adolescents.
AB  - Benzene is a ubiquitous environmental pollutant with various health effects. It
      is reported that benzene exposure might be associated with insulin resistance in
      elderly adults. The aim of this study is to investigate the association between
      urinary benzene metabolite, trans, trans-muconic acid (t,t-ma) and markers of
      oxidative stress and insulin resistance in children and adolescents. This cross
      sectional study was conducted in 2017 among 86 children and adolescents, aged 6
      18 years, living in Isfahan, Iran. t,t-ma was measured as urinary benzene
      metabolite and homeostasis model assessment (HOMA-IR) was determined as an index
      of insulin resistance. Moreover, malondialdehyde (MDA) and superoxide dismutase
      (SOD) were assessed as oxidative stress markers. We found significant association
      between insulin resistance, fasting blood glucose, and fasting blood insulin with
      t,t-ma (p values = 0.002, 0.03, and 0.001, respectively). Results of this study
      indicate that benzene metabolite in higher concentrations in comparison with
      lower concentrations is associated with increased risk of insulin resistance.
      Moreover, after adjustment for age, sex, and household passive smoking,
      statistically significant increase were documented in SOD and MDA (4.49- and 3.54
      fold, respectively) in intermediate levels of t,t-ma vs. low levels of t,t-ma (p
      values = 0.01 and 0.034, respectively). To the best of our knowledge, this is the
      first study in its kind in the pediatric age group. It showed that benzene
      exposures, even in environmental levels, might be associated with insulin
      resistance and oxidative stress in children and adolescents. Further longitudinal
      studies are necessary to assess the clinical impacts of this finding.

PMID- 30280348
TI  - The legacy of pesticides and POPs stockpiles-a threat to health and the
      environment.

PMID- 30280349
TI  - Interactions Between Biological Products and Product Packaging and Potential
      Approaches to Overcome Them.
AB  - Biological products such as protein-based biopharmaceuticals are playing an
      important role in the healthcare and pharmaceutical industry. The interaction
      between biological products and packaging materials has become the focus of many
      studies since it can reduce the effectiveness of biological products. These
      interactions are heavily influenced by the surface properties and physicochemical
      nature of the therapeutic agents and the packaging materials. Therefore, it is
      critical to understand the interactions between packaging materials and
      biological products in order to design biocompatible packaging materials and
      develop approaches to minimize adverse interactions. We describe the interactions
      that occur when using several common packaging materials, including glass and
      polymer. We discuss the interaction between these materials and biological
      products such as blood, blood derivatives, recombinant proteins, monoclonal
      antibodies, and gene therapeutics. We also summarize approaches for overcoming
      these interactions. Understanding the interactions between biological materials
      and packaging materials is critical for the development of novel packaging
      materials that improve the safety of pharmaceutical products.

PMID- 30280350
TI  - Nanocarrier-Based Combination Chemotherapy for Resistant Tumor: Development,
      Characterization, and Ex Vivo Cytotoxicity Assessment.
AB  - A folic acid-conjugated paclitaxel (PTX)-doxorubicin (DOX)-loaded nanostructured
      lipid carrier(s) (FA-PTX-DOX NLCs) were prepared by using emulsion-evaporation
      method and extensively characterized for particle size, polydispersity index,
      zeta potential, and % entrapment efficiency which were found to be 196 +/- 2.5
      nm, 0.214 +/- 0.04, +23.4 +/- 0.3 mV and 88.3 +/- 0.2% (PTX), and 89.6 +/- 0.5%
      (DOX) respectively. In vitro drug release study of optimized formulation was
      carried out using dialysis tube method. FA-conjugated PTX-DOX-loaded NLCs showed
      75.6 and 78.4% (cumulative drug release) of PTX and DOX respectively in 72 h in
      PBS (pH 7.4)/methanol (7:3), while in the case of FA-conjugated PTX-DOX-loaded
      NLCs, cumulative drug release recorded was 80.4 and 82.8% of PTX and DOX
      respectively in 72 h in PBS (pH 4.0)/methanol (7:3). Further, the formulation(s)
      were evaluated for ex vivo cytotoxicity study. The cytotoxicity assay in
      doxorubicin-resistant human breast cancer MCF-7/ADR cell lines revealed lowest
      GI50 value of FA-D-P NLCs which was 1.04 +/- 0.012 MUg/ml, followed by D-P NLCs
      and D-P solution with GI50 values of 3.12 +/- 0.023 and 3.89 +/- 0.007 MUg/ml,
      respectively. Findings indicated that the folic acid-conjugated PTX and DOX co
      loaded NLCs exhibited lower GI50 values as compared to unconjugated PTX and DOX
      co-loaded NLCs; thus, they have relatively potential anticancer efficacy against
      resistant tumor.

PMID- 30280351
TI  - Intratumoral Injection Administration of Irinotecan-Loaded Microspheres: In Vitro
      and In Vivo Evaluation.
AB  - To reduce the toxic and side effects of intravenous chemotherapeutic drugs on the
      tumor-patients, the aims of this study were to design and study intratumor
      administrated irinotecan-loaded PLGA microspheres (CPT-11-PLGA-MS) in vitro and
      in vivo according to the structure characteristics of CPT-11. PLGA microspheres
      containing irinotecan were prepared by emulsion solvent evaporation method and
      evaluated in terms of their morphology, particle size analysis, in vitro drug
      release, drug retention and leakage studies in vivo, and pharmacodynamics
      studies. The CPT-11-PLGA-MS were spherical with mean size of 9.29 +/- 0.02 MUm,
      and average encapsulation efficiency were measured of 77.97 +/- 1.26% along with
      the average drug loading of 7.08 +/- 0.11%. DSC results indicated that the drug
      existed in the phase of uncrystallization in the microspheres. The formulation of
      CPT-11-PLGA-MS could prolong the in vitro drug release to 16 days following
      Weibull equation. In CPT-11-PLGA-MS after intratumor injection administration was
      significantly improved. The results demonstrated that the slow-sustained release
      of CPT-11-PLGA-MS in tumor tissue after intratumor injection of microspheres can
      reduce the drug leakage to the circulation system, maintain the drug retention,
      and improve the therapeutic effect, which could become a promising drug delivery
      system for CPT-11 and could maintain the most effective concentration at the
      target site to maximum limit.

PMID- 30280352
TI  - Comparing a Statistical Model and Bayesian Approach to Establish the Design Space
      for the Coating of Ciprofloxacin HCl Beads at Different Scales of Production.
AB  - The primary objective of this study was to compare two methods for establishing a
      design space for critical process parameters that affect ethylcellulose film
      coating of multiparticulate beads and assess this design space validity across
      manufacturing scales. While there are many factors that can affect film coating,
      this study will focus on the effects processing conditions have on the quality
      and extent of film formation, as evaluated by their impact coating yield and drug
      release. Ciprofloxacin HCl layered beads were utilized as an active substrate
      core, ethylcellulose aqueous dispersion as a controlled release polymer, and
      triethyl citrate as a plasticizer. Thirty experiments were conducted using a
      central composite design to optimize the coating process and map the response
      surface to build a design space using either statistical least squares or a
      Bayesian approach. The response surface was fitted using a linear two-factor
      interaction model with spraying temperature, curing temperature, and curing time
      as significant model terms. The design spaces established by the two approaches
      were in close agreement with the statistical least squares approach being more
      conservative than the Bayesian approach. The design space established for the
      critical process parameters using small-scale batches was tested using scale-up
      batches and found to be scale-independent. The robustness of the design space was
      confirmed across scales and was successfully utilized to establish process
      signature for the coating process.

PMID- 30280353
TI  - Enhanced Oral Bioavailability of Chlormadinone Acetate through a Self
      Microemulsifying Drug Delivery System for a Potential Dose Reduction.
AB  - Chlormadinone acetate (CMA) is a derivative of the naturally secreted hormone
      progesterone and exhibits reliable contraceptive and non-contraceptive benefits.
      Although the marketed product of CMA as oral tablets under the trade name
      Belara(r) has been highly successful, there is still room for further
      improvements in oral bioavailability and a reduction in the clinical dose to
      decrease related adverse effects. In the current study, a CMA-based self
      microemulsifying drug delivery system (SMEDDS) was developed using 32% ethyl
      oleate as an oil phase, 40% Tween-80 as a surfactant, and 12% Transcutol P
      combined with 16% PEG400 as a cosurfactant, resulting in spherical droplets with
      a z-average particle size of 38.92 nm and an average zeta potential of - 3.18 mv.
      The in vitro release rate of CMA from CMA-SMEDDS in different media (distilled
      water, HCl solution at pH 1.2, phosphate buffers at pH 4.5 and pH 6.8) was
      significantly faster than that from Belara(r) in the first 15 min. A
      pharmacokinetic study in rats showed that the Cmax and AUC of CMA-SMEDDS were
      significantly higher (P < 0.01) than those of Belara(r), with a 1.98-fold
      increase in oral bioavailability. In comparison with Belara(r), the developed CMA
      SMEDDS showed promising release profiles both in vitro and in vivo, which could
      potentially be useful in enhancing oral bioavailability and reducing the clinical
      dose of CMA.

PMID- 30280354
TI  - Preparation and Characterization of an Oral Vaccine Formulation Using
      Electrosprayed Chitosan Microparticles.
AB  - Chitosan particles loaded with the antigen ovalbumin (OVA) and the adjuvant Quil
      A were produced by electrospray, using mixtures of water/ethanol/acetic acid as a
      solvent. Three different chitosans designed as HMC+70, HMC+85, and HMC+90 (called
      as 705010, 855010, and 905010) were tested and its efficacy to be used in oral
      vaccine delivery applications was investigated. The morphology, size, and zeta
      potential of the produced particles were investigated, together with the
      encapsulation efficiency and release of OVA from the three chitosan formulations.
      Moreover, the mucoadhesion and cytotoxicity of the chitosan microparticles was
      examined. All the three formulations with OVA and Quil-A were in the micrometer
      size range and had a positive zeta potential between 46 and 75 mV. Furthermore,
      all the three formulations displayed encapsulation efficiencies above 80% and the
      release of OVA over a period of 80 h was observed to be between 38 and 47%. None
      of the developed formulations exhibited high mucoadhesive properties, either
      cytotoxicity. The formulation prepared with HMC+70, OVA, and Quil-A had the
      highest stability within 2 h in buffer solution, as measured by dynamic light
      scattering. The electrosprayed formulation consisting of HMC+70 with OVA and Quil
      A showed to be the most promising as an oral vaccine system.

PMID- 30280355
TI  - Aggregate Elasticity and Tabletability of Molecular Solids: a Validation and
      Application of Powder Brillouin Light Scattering.
AB  - Describing the elastic deformation of single-crystal molecular solids under
      stress requires a comprehensive determination of the fourth-rank stiffness tensor
      (Cijkl). Single crystals are, however, rarely utilized in industrial
      applications, and thus averaging techniques (e.g., the Voigt or Reuss approach)
      are employed to reduce the Cijkl (or its inverse Sijkl) to polycrystalline
      aggregate mechanical moduli. With increasing elastic anisotropy, the Voigt and
      Reuss-averaged aggregate moduli can diverge dramatically and, provided that drug
      molecules almost exclusively crystallize into low-symmetry space groups, warrants
      a significant need for accurate aggregate mechanical moduli. This elasticity
      data, which currently is largely absent for pharmaceutical materials, is expected
      to aid understanding how materials respond to direct compression and tablet
      formation. Powder Brillouin light scattering (p-BLS) has recently demonstrated
      facile access to porosity-independent, aggregate mechanical moduli. In this
      study, we extend our previous p-BLS model for obtaining mechanical properties and
      validate our approach against a broad library of molecular solids with diverse
      intermolecular interaction topologies and with previously determined Cijkl which
      permits benchmarking our results. Our Young's and shear moduli determined with p
      BLS strongly correlate, with limited bias (i.e., a near 1:1 relation), with the
      Voigt-averaged Young's and shear moduli determined using the Cijkl. Through
      follow-on tabletability studies, we introduce initial classifications of
      tabletability behavior based on the results of our p-BLS studies and the apparent
      elastic anisotropy. With further development, this approach represents a robust
      and novel method to potentially identify materials for optimum tabletability at
      early developmental stages.

PMID- 30280356
TI  - Investigating a Novel Hot Melt Extrusion-Based Drying Technique to Solidify an
      Amorphous Nanosuspension Using Design of Experiment Methodology.
AB  - The hot melt extrusion (HME) technology was explored and optimized to solidify an
      amorphous nanosuspension using Quality by Design (QbD) methodology. A design of
      experiments (DoE) approach was used to perform a set of 15 experiments, varying
      independent variables (feed rate, input temperature, and screw speed) within a
      design space. Redispersibility index (RDI), moisture content, and process yield
      constituted the critical quality attributes (CQAs) of the experimental design.
      Regression analysis and ANOVA were employed to identify and estimate significant
      main effects and two-way interactions, and model the process of HME drying for
      predictive purposes. The optimized HME-dried end product was characterized for
      physicochemical properties using differential scanning calorimetry (DSC), X-ray
      powder diffractions (XRPD), polarized light microscopy (PLM), Fourier transform
      infrared spectroscopy (FTIR), and in vitro dissolution studies. The statistical
      analysis reveals feed rate and input temperature as significant independent
      variables, critically influencing RDI and moisture content of solidified end
      product. The model developed for process yield was insignificant at a p-value of
      0.05. The API retained its amorphous nature after the extrusion process which was
      confirmed using DSC and XRPD techniques. PLM was unsuitable to differentiate and
      determine crystallinity of drug moiety in the presence of a semi-crystalline
      bulking agent, microcrystalline cellulose (MCC). In vitro dissolution study
      depicted solubility and dissolution enhancement for HME-dried amorphous
      nanosuspension in both the dissolution media which can be attributed to amorphous
      nature of nanosized drug particles. A well-designed study implemented by DoE
      aided in developing a robust and novel HME technique to dry aqueous
      nanosuspension.

PMID- 30280358
TI  - Intranasal Surface-Modified Mosapride Citrate-Loaded Nanostructured Lipid
      Carriers (MOS-SMNLCs) for Treatment of Reflux Diseases: In vitro Optimization,
      Pharmacodynamics, and Pharmacokinetic Studies.
AB  - Gastroesophageal reflux disease (GERD) is an esophageal injury occurred when the
      stomach contents reflux abnormally into the esophagus. GERD complications include
      esophageal adenocarcinoma. Mosapride (MOS) is a safe prokinetic agent potentially
      used to treat GERD. Yet, its low solubility and bioavailability due to extensive
      first-pass metabolism limits its applications. This study aimed to formulate MOS
      nanostructured lipid carriers (MOS-NLCs) via the intranasal route to improve its
      bioavailability. Melt-emulsification low temperature-solidification technique
      using 23 full factorial design was adopted to formulate MOS-NLCs. Eight formulae
      were prepared and assessed in terms of entrapment efficiency (%EE), particle
      size, and in vitro release. Glycerol addition significantly reduced the particle
      sizes and improved %EE and %drug released. Surface modification using chitosan
      was applied. The optimized MOS surface-modified nanostructured lipid carriers
      (MOS-SMNLCs-F7)(stearic acid, 4% glycerol, 0.5% LuterolF127, 0.5% chitosan)
      showed low particle size 413.8 nm +/- 11.46 nm and high %EE 90.19% +/- 0.06% and
      a threefold increase in permeation of MOS with respect to the drug suspension.
      MOS-SMNLCs (F7) was also evaluated for its bioavailability compared with drug
      suspension and commercial product. Statistical analysis revealed a significant
      increase in gastric emptying rate to be 21.54 +/- 1.88 contractions/min compared
      with10.02 +/- 0.62 contractions/min and 8.9 +/- 0.72 contractions/min for drug
      suspension and oral marketed product respectively. Pharmacokinetic studies showed
      2.44-fold rise in bioavailability as compared to MOS suspension and 4.54-fold as
      compared to the oral marketed product. In vitro/in vivo studies proven to level A
      correlation between in vitro permeation through sheep nasal mucosa and in vivo
      absorption. Therefore, MOS-SMNLCs could be considered a step forward towards
      enhancing the clinical efficacy of Mosapride.

PMID- 30280357
TI  - Nano-lipid Complex of Rutin: Development, Characterisation and In Vivo
      Investigation of Hepatoprotective, Antioxidant Activity and Bioavailability Study
      in Rats.
AB  - The current study was aimed to develop an amphiphilic drug-lipid nano-complex of
      rutin:egg phosphatidylcholine (EPC) to enhance its poor absorption and
      bioavailability, and investigated the impact of the complex on hepatoprotective
      and antioxidant activity. Rutin nano-complexes were prepared by solvent
      evaporation, salting out and lyophilisation methods and compared for the complex
      formation. For the selected lyophilisation method, principal solvent DMSO, co
      solvent (t-butyl alcohol) and rutin:EPC ratios (1:1, 1:2 and 1:3) were selected
      after optimisation. The properties of the nano-complexes such as complexation,
      thermal behaviour, surface morphology, molecular crystallinity, particle size,
      zeta potential, drug content, solubility, in vitro stability study, in vitro drug
      release, in vitro and in vivo antioxidant study, in vivo hepatoprotective
      activity and oral bioavailability/pharmacokinetic studies were investigated.
      Rutin nano-complexes were developed successfully via the lyophilisation method
      and found to be in nanometric range. Rutin nano-complexes significantly improved
      the solubility and in vitro drug release, and kinetic studies confirmed the
      diffusion-controlled release of the drug from the formulation. The nano-complex
      showed better antioxidant activity in vitro and exhibited well in vitro stability
      in different pH media. The in vivo study showed better hepatoprotective activity
      of the formulation compared to pure rutin at the same dose levels with improved
      oral bioavailability. Carbon tetrachloride (CCl4)-treated animals (group II)
      failed to restore the normal levels of serum hepatic marker enzymes and liver
      antioxidant enzyme compared to the nano-complex-treated animals. The results
      obtained from solubility, hepatoprotective activity and oral bioavailability
      studies proved the better efficacy of the nano-complex compared to the pure drug.

PMID- 30280359
TI  - In-Line Film Coating Thickness Estimation of Minitablets in a Fluid-Bed Coating
      Equipment.
AB  - Film coating thickness of minitablets was estimated in-line during coating in a
      fluid-bed equipment by means of visual imaging. An existing, commercially
      available image acquisition system was used for image acquisition, while
      dedicated image analysis and data analysis methods were developed for this
      purpose. The methods were first tested against simulated minitablet's images and
      after that examined on a laboratory-scale fluid-bed Wurster coating process. An
      observation window cleaning mechanism was developed for this purpose. Six batches
      of minitablets were coated in total, using two different dispersions, where for
      the second dispersion coating endpoint was determined based on the in-line
      measurement. Coating thickness estimates were calculated from the increasing size
      distributions of the minitablet's major and minor lengths, assessed from the
      acquired images. Information on both the minitablet's average band and average
      cap coating thicknesses was obtained. The in-line coating thickness estimates
      were compared to the coating thickness weight gain calculations and the optical
      microscope measurements as a reference method. Average band coating thickness
      estimate was found the most accurate in comparison to microscope measurements,
      with root mean square error of 1.30 MUm. The window cleaning mechanism was
      crucial for the accuracy of the in-line measurements as was evident from the
      corresponding decrease of the root mean square error (9.52 MUm, band coating
      thickness). The presented visual imaging approach exhibits accuracy of at least 2
      MUm and is not susceptible to coating formulation or color variations. It
      presents a promising alternative to other existing techniques for the in-line
      coating thickness estimation.

PMID- 30280360
TI  - Can we now say that commonalities between restless leg syndrome and migraine
      exist?
AB  - The recent manuscript by Xinglong Yang and colleagues provided the first
      relatively reliable estimate of restless leg syndrome (RLS) prevalence among
      migraine sufferers, which was estimated at 19% (95% CI 14-24%). The implications
      of the association between the two conditions are wide, and call for further
      action aimed to address common disease mechanism-associated conditions such as
      sleep-related ones and associated burden.

PMID- 30280361
TI  - Hyperresponsivity in migraine: a network dysfunction or an analytic cognitive
      style-connected feature?

PMID- 30280362
TI  - Olfactory bulb atrophy in migraine patients.
AB  - OBJECTIVE: Osmophobia and headache triggered by odors are commonly seen in
      migraine, and these are symptoms that differentiate migraine from other primary
      headaches. Since these odor-related symptoms are disease-specific, we aimed to
      measure the volume of olfactory bulb and depth of olfactory sulcus in migraine
      patients. PATIENTS AND METHOD: A total of 93 subjects, consisting of 62 episodic
      migraine (32 with osmophobia, 30 without osmophobia) patients and 31 healthy
      controls, were included in this study. Diagnosis and classification of migraine
      were performed according to the beta version criteria of International
      Classification of Headache Disorders (ICHD-3 Beta version). Beck depression and
      beck anxiety inventory were applied to the patients, and the measurement of
      bilateral olfactory bulb volume (OBV) and olfactory sulcus depth (OSD) was
      performed manually in the brain magnetic resonance imaging (MRI). RESULTS: More
      significantly in the left OBV, low OBV has been determined in migraine patients
      compared to the control group (p < 0.001, p = 0.020). When migraine patients with
      or without osmophobia were compared to the control group; OBV was determined to
      be the lowest in migraine group with osmophobia, and left-weighted bilateral OBV
      was determined to be low (p < 0.001, p = 0.046). No statistically significant
      difference was determined between groups in OSD measurements (p = 0.646, p =
      0.490). CONCLUSION: Left-weighted bilateral OBV atrophy determined in migraine
      patients may be guiding for the clarification of migraine pathophysiology and
      enlightening of the relation between migraine and odor.

PMID- 30280363
TI  - Having Siblings is Associated with Better Social Functioning in Autism Spectrum
      Disorder.
AB  - Sibling relationships play a unique developmental role, especially in emotional
      and social domains. In autism spectrum disorder (ASD), social-communication
      skills are often impaired in comparison to typical development. Therefore,
      studying siblings' effects on social skills of the child with ASD is important.
      This retrospective study examined how autism severity and functioning were
      affected by having older and younger sibling/s, the sex of the index child and of
      the sibling, and the number of siblings. The study population included 150
      participants with ASD (mean age = 4:0 +/- 1:6), divided into three equal groups
      (no sibling, older and younger siblings), matched for cognitive level. The
      evaluation included neurological and standardized behavioral, cognitive, and
      functional assessments. Children with ASD with older siblings showed less severe
      social interaction deficits and better social adaptive skills than only children.
      No significant differences in autism severity and adaptive functioning were noted
      between the group with younger siblings and the other groups. The more older
      siblings the affected child had, the better their social functioning. The sex of
      the participants with ASD and that of the sibling were not associated with social
      functioning. Social interaction deficits, the presence of older or younger
      siblings for children with ASD, and higher cognitive ability contributed
      significantly to the explained variance (48.9%) in social adaptive skills. These
      findings emphasize that older siblings positively influence the social skills of
      their younger sibling with ASD. The effect of typically developing younger
      siblings was modest and seen only in children with ASD and better cognition.

PMID- 30280364
TI  - Children Sleep and Antisocial Behavior: Differential Association of Sleep with
      Aggression and Rule-Breaking.
AB  - There is a strong relationship between sleep and behavioral problems. These
      findings are often interpreted via environmental explanations, such that poor
      sleep directly exacerbates or causes symptoms of aggression and behavior
      problems. However, there are other possible explanations, such that the genes
      predicting poor sleep also predict aggression or rule-breaking. The current study
      sought to elucidate the origin of this relationship. The sample was composed of
      1030 twin pairs (426 monozygotic and 604 dizygotic). The sample was 51.3% male
      with a mean age of 8.06 years (range 6-11.96; SD = 1.45). Aggression, rule
      breaking and sleep were assessed through the Child Behavior Checklist (CBCL). We
      fitted bivariate Cholesky genetic models to the data, decomposing the variance
      within, and the covariance among, aggression, rule-breaking, and sleep
      functioning into their genetic and environmental components. Genetic correlations
      between all sleep variables and aggression were significant and moderate to large
      in magnitude, but mostly small and non-significant between sleep and rule
      breaking. We did not find evidence of a causal or environmental relationship
      between the majority of sleep variables and aggression, but rather clear evidence
      of genetic pleiotropy. However, the pattern of associations between rule-breaking
      and sleep measures was less consistent. Aggression and rule-breaking appear to be
      differentially associated with sleep.

PMID- 30280365
TI  - Using Early Childhood Behavior Problems to Predict Adult Convictions.
AB  - The current study examined whether teacher and parent ratings of externalizing
      behavior during kindergarten and 1st grade accurately predicted the presence of
      adult convictions by age 25. Data were collected as part of the Fast Track
      Project. Schools were identified based on poverty and crime rates in four
      locations: Durham, NC, Nashville, TN, Seattle, WA, and rural, central PA. Teacher
      and parent screening measures of externalizing behavior were collected at the end
      of kindergarten and 1st grade. ROC curves were used to visually depict the
      tradeoff between sensitivity and specificity and best model fit was determined.
      Five of the six combinations of screen scores across time points and raters met
      both the specificity and sensitivity cutoffs for a well-performing screening
      tool. When data were examined within each site separately, screen scores
      performed better in sites with high base rates and models including single
      teacher screens accurately predicted convictions. Similarly, screen scores
      performed better and could be used more parsimoniously for males, but not females
      (whose base rates were lower in this sample). Overall, results indicated that
      early elementary screens for conduct problems perform remarkably well when
      predicting criminal convictions 20 years later. However, because of variations in
      base rates, screens operated differently by gender and location. The results
      indicated that for populations with high base rates, convictions can be
      accurately predicted with as little as one teacher screen taken during
      kindergarten or 1st grade, increasing the cost-effectiveness of preventative
      interventions.

PMID- 30280367
TI  - PF-05280014: A Trastuzumab Biosimilar.
AB  - PF-05280014 (TrazimeraTM) is the fourth biosimilar of the reference anti-HER2
      antibody trastuzumab to be approved in the EU. It is approved for use in all
      indications for which reference trastuzumab is approved, including HER2-positive
      metastatic or early breast cancer and metastatic gastric cancer. PF-05280014 has
      similar physicochemical and pharmacodynamic properties to those of reference
      trastuzumab, and the pharmacokinetic similarity of the agents has been shown in
      women with metastatic or early HER2-positive breast cancer and healthy male
      volunteers. The efficacy of PF-05280014 was equivalent to that of reference
      trastuzumab in women with HER2-positive metastatic breast cancer and was
      comparable to that of reference trastuzumab in those with HER2-positive early
      breast cancer. The immunogenicity, tolerability and safety profiles of PF
      05280014 were similar to those of reference trastuzumab. The role of reference
      trastuzumab in the management of HER2-positive breast and gastric cancers is well
      established and PF-05280014 provides an effective biosimilar alternative for
      patients requiring trastuzumab therapy.

PMID- 30280366
TI  - Gasdermin Family: a Promising Therapeutic Target for Stroke.
AB  - Stroke is one of the leading causes of death worldwide and therapies are limited.
      According to the mechanisms underlying stroke, direct cell demise, destruction of
      organelles, blood-brain barrier disruption, neuroinflammation are potential
      therapeutic targets. Gasdermin (GSDM) family is a series of recently discovered
      proteins, which acts as the executor of pyroptosis and protagonist of membrane
      pore formation. It can be cleaved by inflammatory caspases that are activated by
      multi-protein complexes, named as inflammasomes, and divided into two domains.
      The N-terminal domain interacts with lipid localized in the plasma membrane as
      well as organelle membrane and perforates them. After the formation of pores, the
      dysfunctional structures suffer lytic death and their contents are released. In
      this review, we discuss the biological characteristic of GSDM family and their
      possible roles in stroke-induced brain injury, and based on the review, we
      hypothesize the feasibility of using GSDMs as a potential target for stroke
      treatment.

PMID- 30280368
TI  - The efficacy and safety of total glucosides of peony in the treatment of primary
      Sjogren's syndrome: a multi-center, randomized, double-blinded, placebo
      controlled clinical trial.
AB  - To evaluate the efficacy and safety of total glucosides of peony (TGP) in adults
      with primary Sjogren's syndrome (pSS). A multi-center, randomized, double
      blinded, placebo-controlled study was conducted between March 2012 and July 2014
      at ten Chinese hospitals. In total, 320 pSS patients-classified according to the
      2002 American-European Consensus Group Criteria-were randomized (2:1 ratio) to
      receive TGP(600 mg, tid) in the TGP group or placebo for 24 weeks in the placebo
      group. Study personnel, investigators, and patients were blinded to the treatment
      grouping. The primary endpoint was the improvement of EULAR Sjogren's Syndrome
      Patient Reported Index (ESSPRI) at week 24. The secondary endpoints were dry
      eyes/mouth/skin/nose/throat/vagina visual analogue scale (VAS), pain and
      discomfort VAS, fatigue VAS, mental discomfort VAS, patient global assessment
      (PGA), EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI), Schirmer's test,
      basal/stimulated salivary flow-rate values, and erythrocyte sedimentation rate
      (ESR). All adverse events were recorded during the trial period. ESSPRI improved
      more in the TGP than the placebo group (p < 0.001). Dry eyes/throat/vagina VAS,
      fatigue VAS, mental discomfort VAS, PGA, Schirmer's test, and ESR also improved
      more in the TGP group than in the placebo group (all p < 0.05). Stimulated
      salivary flow-rate values increased in the TGP group at week 12 but not at week
      24. Adverse events in TGP group were 10.9%. TGP can alleviate some dryness
      symptoms as well as disease activity in pSS patients over 24 weeks. TGP was well
      tolerated by study subjects. TGP seems to be an effective and safe treatment for
      pSS.

PMID- 30280370
TI  - Introduction of a uniform record keeping practice for rheumatology clinics in Sri
      Lanka-an ILAR project.
AB  - In Sri Lanka, record keeping in rheumatology clinics is purely paper-based.
      Clinic record books are given to patients, and the hospital does not retain
      clinical data. Different clinics and different rheumatology specialists practice
      different formats of record keeping in Sri Lanka. This project was aimed to
      develop a uniform record keeping system which can be used in all government
      rheumatology clinics in Sri Lanka. Project was carried out in two phases. First
      phase was carried out in seven rheumatology clinics to identify deficiencies in
      existing practice of record keeping in rheumatoid arthritis (RA),
      spondyloarthritis (SPA), and systemic lupus erythematosus (SLE). Second phase was
      to develop new clinic documents and a computer-based system, using the findings
      of the first phase. Recording of classification criteria at the time of diagnosis
      was 40.6% for RA and 90.3% for SLE. Initial clinical notes were not available in
      18.3% of RA patients. Recording of individual classification criteria in SPA was
      ranged between 10% and70%, and it was 100% for arthritis. During second phase,
      new paper-based and computer-based record keeping systems were developed.
      Existing practice of record keeping is incomplete, especially in RA and SPA. The
      necessity of new, uniform record keeping system was recognized. Paper-based and
      computer-based record keeping systems acceptable to specialist rheumatologists,
      medical officers, and the Ministry of Health were developed and tested. The newly
      developed paper-based system is being used nationally while the electronic system
      is yet to introduced.

PMID- 30280369
TI  - Chronic lung disease in U.S. Veterans with rheumatoid arthritis and the impact on
      survival.
AB  - Assess the impact of chronic lung diseases (CLD) on survival in rheumatoid
      arthritis (RA). Among participants in the Veterans Affairs Rheumatoid Arthritis
      (VARA) Registry, a prospective cohort of U.S. Veterans with RA, we identified CLD
      and cardiovascular disease (CVD) using administrative and registry data.
      Demographics, smoking status, RA characteristics including Disease Activity Score
      in 28 joints (DAS28), and disease-modifying anti-rheumatic drug (DMARD) use were
      obtained from registry data, which were linked to the National Death Index to
      obtain vital status. We evaluated associations of CLD with survival using the
      multivariable Cox regression models. Among a large (n = 2053), male-predominant
      (91%) RA cohort, 554 (27%) had CLD at enrollment. Mortality risk was increased
      1.51-fold (95% CI 1.26-1.81) in RA patients with CLD after multivariable
      adjustment, a risk that was similar to that observed with CVD (HR CLD alone 1.46
      [1.03-2.06]; CVD alone 1.62 [1.35-1.94]). Survival was significantly reduced in
      those with interstitial lung disease (ILD) as well as other forms of CLD.
      Mortality risk with methotrexate and biologic use was not different in those with
      CLD compared to those without (p interaction >= 0.15) using multiple exposure
      definitions and propensity score adjustment. Mortality risk is significantly
      increased in RA patients with CLD. This risk is attributable not only to ILD but
      also to other chronic lung conditions and does not appear to be substantially
      greater in those receiving methotrexate or biologic therapies. Comorbid lung
      disease should be targeted as a means of improving long-term outcomes in RA.

PMID- 30280372
TI  - Cobalt ions stimulate a fibrotic response through matrix remodelling, fibroblast
      contraction and release of pro-fibrotic signals from macrophages.
AB  - Many studies report the adverse responses to metal-on-metal (MoM) hip prostheses,
      with tissues surrounding failed MoM hip prostheses revealing abundant tissue
      necrosis and fibrosis. These local effects appear to be initiated by metal ions
      released from the prosthesis causing the secretion of inflammatory mediators.
      However, little is known about the effect of the metal ions on tissue remodelling
      and pseudotumor formation, which are also associated with the failure of MoM hip
      prostheses. The peri-prosthetic soft tissue masses can lead to pain, swelling,
      limited range of joint movement and extensive tissue lesion. To elucidate this
      cellular response, a multidisciplinary approach using both two- and three
      dimensional (2D and 3D) in vitro culture systems was employed to study the
      effects of Co2+ and Cr3+ on human fibroblast activation and mechanobiology. Co2+
      induced a fibrotic response, characterised by cytoskeletal remodelling and
      enhanced collagen matrix contraction. This was associated with increased cell
      stiffness and contractile forces as measured by atomic force microscopy and
      traction force microscopy, respectively. These effects were triggered by the
      generation of reactive oxygen species (ROS). Moreover, this fibrotic response was
      enhanced in the presence of macrophages, which increased the prevalence of a
      smooth muscle actin (a-SMA)-positive fibroblasts and collagen synthesis. Cr3+ did
      not show any significant effect on fibroblast activation. Co2+ promoted matrix
      remodelling by fibroblasts that was further enhanced by macrophage signalling.
      Use of alternative implant materials or manipulation of this fibrotic response
      could provide an opportunity for enhancing the success of prostheses utilising
      CoCr alloys.

PMID- 30280373
TI  - Circumaortic left renal vein (circumaortic renal collar) associated with the
      presence of vascular anomalies: a case series and review of literature.
AB  - Renal vessels exhibit a high degree of anatomical variations in terms of their
      number, level of origin, diameter and topographical relationships. In particular,
      it applies to the left renal vein which can take retroaortic or even circumaortic
      placement. Anatomical variations of the left renal vein may be of great clinical
      significance, particularly in the case of renal transplantation, retroperitoneal
      surgery as well as vascular or diagnostic procedures. Thus, the aim of this
      report was to present a complete anatomical description of two cases of the
      circumaortic left renal vein (circumaortic renal collar) co-existing with the
      presence of various vascular anomalies. In the first case, the circumaortic renal
      collar was connected via a large anastomosis with the hemiazygos vein and was
      associated with the presence of the supernumerary left renal artery located below
      the main left renal artery. In the second case, the circumaortic renal collar was
      accompanied by the renal artery dividing close to its origin. Moreover, in the
      latter case, the fusiform aneurysm of the abdominal aorta was observed. In both
      cases, the circumaortic left renal vein began as a single and short trunk. On its
      further course, the initial segment of the circumaortic left renal vein was
      divided into two limbs - anterior (anterior left renal vein) and posterior
      (posterior left renal vein). Both anterior and posterior limb of the circumaortic
      left renal vein opened into the inferior vena cava.

PMID- 30280374
TI  - Assessment of paranasal sinus parameters according to ancient skulls' gender and
      age by using cone beam computed tomography.
AB  - BACKGROUND: The aim of this study was to determine whether paranasal sinus
      dimensions and volume can be useful to identify gender and age estimation for
      ancient skulls using cone beam computed tomography (CBCT) images. MATERIALS AND
      METHODS: CBCT scans of 32 ancient skulls from app. 1000 years of age were
      included in this retrospective study. The gender and age estimation of the skulls
      were made by an independent anthropologist which was served as the gold standard.
      Paranasal sinuses dimensions (width and height) and volumes of each sinus were
      measured from the CBCT data set that were linked to the 3D rendering software
      (Anatomage, Invivo 5.2). All measurements were performed by an independent
      observer. Intra-observer analysis was made. Mann-Whitney test and Kruskal-Wallis
      tests were used to compare paranasal sinus parameters in terms of age estimation
      and gender (p<0.05). RESULTS: The results demonstrated no statistically
      significant difference between measurements (p<0.05). The measurements were found
      to be high reproducibility. The mean volumes for frontal and sphenoid sinus were
      found to be higher in males. The distance from anterior-posterior wall of
      sphenoid sinus in axial sections is larger in males (p>0.05). The frontal sinus
      width and volume increased statistically with age above 60 yrs. of age (p>0.05).
      CONCLUSIONS: The paranasal volume and dimensions measurements from CBCT data can
      be a promising technique to determine gender and age estimation from ancient
      skulls because of its lower voxel sizes and higher resolution.

PMID- 30280371
TI  - Switchable DNA-origami nanostructures that respond to their environment and their
      applications.
AB  - Structural DNA nanotechnology, in which Watson-Crick base pairing drives the
      formation of self-assembling nanostructures, has rapidly expanded in complexity
      and functionality since its inception in 1981. DNA nanostructures can now be made
      in arbitrary three-dimensional shapes and used to scaffold many other functional
      molecules such as proteins, metallic nanoparticles, polymers, fluorescent dyes
      and small molecules. In parallel, the field of dynamic DNA nanotechnology has
      built DNA circuits, motors and switches. More recently, these two areas have
      begun to merge-to produce switchable DNA nanostructures, which change state in
      response to their environment. In this review, we summarise switchable DNA
      nanostructures into two major classes based on response type: molecular actuation
      triggered by local chemical changes such as pH or concentration and external
      actuation driven by light, electric or magnetic fields. While molecular actuation
      has been well explored, external actuation of DNA nanostructures is a relatively
      new area that allows for the remote control of nanoscale devices. We discuss
      recent applications for DNA nanostructures where switching is used to perform
      specific functions-such as opening a capsule to deliver a molecular payload to a
      target cell. We then discuss challenges and future directions towards achieving
      synthetic nanomachines with complexity on the level of the protein machinery in
      living cells.

PMID- 30280377
TI  - Comparative effectiveness research using registries, databases, and networks in
      women's and children's health: Time to embrace the future?

PMID- 30280376
TI  - GRIN2D variants in three cases of developmental and epileptic encephalopathy.
AB  - N-methyl-d-aspartate (NMDA) receptors are glutamate-activated ion channels that
      are widely distributed in the central nervous system and essential for brain
      development and function. Dysfunction of NMDA receptors has been associated with
      various neurodevelopmental disorders. Recently, a de novo recurrent GRIN2D
      missense variant was found in two unrelated patients with developmental and
      epileptic encephalopathy. In this study, we identified by whole exome sequencing
      novel heterozygous GRIN2D missense variants in three unrelated patients with
      severe developmental delay and intractable epilepsy. All altered residues were
      highly conserved across vertebrates and among the four GluN2 subunits. Structural
      consideration indicated that all three variants are probably to impair GluN2D
      function, either by affecting intersubunit interaction or altering channel gating
      activity. We assessed the clinical features of our three cases and compared them
      to those of the two previously reported GRIN2D variant cases, and found that they
      all show similar clinical features. This study provides further evidence of
      GRIN2D variants being causal for epilepsy. Genetic diagnosis for GluN2-related
      disorders may be clinically useful when considering drug therapy targeting NMDA
      receptors.

PMID- 30280378
TI  - Complex effects of laminopathy mutations on nuclear structure and function.
AB  - The nuclear lamins are important members of the intermediate filament (IF) family
      of proteins, involved in structural support and regulation of the nuclear lamina.
      Different mutations in various members of these type V IF proteins produce a
      staggering range of human disease phenotypes, which collectively have been termed
      "laminopathies." Compelling examples are the wide range of inherited disorders
      that result from rare variants in LMNA encoding lamin A/C. These laminopathies
      include skeletal and cardiac muscle disorders, neuropathies, multisystem
      progeroid disorders, and lipodystrophies, of which the latter are associated with
      several metabolic complications. Functions of lamin A/C that have been shown to
      be compromised by distinct mutations in LMNA include loss of nuclear structural
      integrity, altered interaction with transcription factors, and changes to post
      translational processing of pre-lamins. Recently, evidence has emerged that
      certain LMNA mutations, such as those causing partial lipodystrophy, alter the
      interaction between chromatin and lamin A, in turn affecting the spatial
      orientation and distribution of chromatin within the nucleus. Because chromatin
      organization is exquisitely tied to global patterns of gene expression, the
      findings suggest a novel mechanism to explain the tissue-specific impact of a
      subset of laminopathy-associated LMNA mutations.

PMID- 30280379
TI  - Occasional long distance dispersal increases spatial synchrony of population
      cycles.
AB  - Spatially separated populations of the same species often exhibit correlated
      fluctuations in abundance, a phenomenon known as spatial synchrony. Dispersal can
      generate spatial synchrony. In nature, most individuals disperse short distances
      with a minority dispersing long distances. The effect of occasional long distance
      dispersal on synchrony is untested, and theoretical predictions are
      contradictory. Occasional long distance dispersal might either increase both
      overall synchrony and the spatial scale of synchrony, or reduce them. We
      conducted a protist microcosm experiment to test whether occasional long distance
      dispersal increases or decreases overall synchrony and the spatial scale of
      synchrony. We assembled replicate 15-patch ring metapopulations of the protist
      predator Euplotes patella and its protist prey Tetrahymena pyriformis. All
      metapopulations experienced the same dispersal rate, but differed in dispersal
      distance. Some metapopulations experienced strictly short distance (nearest
      neighbour) dispersal, others experienced a mixture of short- and long distance
      dispersal. Occasional long distance dispersal increased overall spatial synchrony
      and the spatial scale of synchrony for both prey and predators, though the
      effects were not statistically significant for predators. As predicted by theory,
      dispersal generated spatial synchrony by entraining the phases of the predator
      prey cycles in different patches, a phenomenon known as phase locking. Our
      results are consistent with theoretical models predicting that occasional long
      distance dispersal increases spatial synchrony. However, our results also
      illustrate that the spatial scale of synchrony need not match the spatial scale
      of the processes generating synchrony. Even strictly short distance dispersal
      maintained high spatial synchrony for many generations at spatial scales much
      longer than the dispersal distance, thanks to phase locking.

PMID- 30280380
TI  - Responses of ant communities to disturbance: Five principles for understanding
      the disturbance dynamics of a globally dominant faunal group.
AB  - Ecological disturbance is fundamental to the dynamics of biological communities,
      yet a conceptual framework for understanding the responses of faunal communities
      to disturbance remains elusive. Here, I propose five principles for understanding
      the disturbance dynamics of ants-a globally dominant faunal group that is widely
      used as bioindicators in land management, which appear to have wide applicability
      to other taxa. These principles are as follows: (1) The most important effects of
      habitat disturbance on ants are typically indirect, through its effects on
      habitat structure, microclimate, resource availability and competitive
      interactions; (2) habitat openness is a key driver of variation in ant
      communities; (3) ant species responses to disturbance are to a large degree
      determined by their responses to habitat openness; (4) the same disturbance will
      have different effects on ants in different habitats, because of different
      impacts on habitat openness; and (5) ant community responses to the same
      disturbance will vary according to ant functional composition and biogeographical
      history in relation to habitat openness. I illustrate these principles using
      results primarily from studies of ant responses to fire, a dominant agent of
      disturbance globally, to provide a common disturbance currency for comparative
      analysis. I argue that many of the principles also apply to other faunal groups
      and so can be considered as general ecological "laws." As is the case for ants,
      many impacts of habitat disturbance on other faunal groups are fundamentally
      related to habitat openness, the effects of disturbance on it and the functional
      composition of species in relation to it.

PMID- 30280381
TI  - Multiple density-dependent processes shape the dynamics of a spatially structured
      amphibian population.
AB  - Understanding the mechanisms that regulate the dynamics of spatially structured
      populations (SSP) is a critical challenge for ecologists and conservation
      managers. Internal population processes such as births and deaths occur at a
      local level, while external processes such as dispersal take place at an inter
      population level. At both levels, density dependence is expected to play a
      critical role. At a patch scale, demographic traits (e.g., survival, breeding
      success) and the population growth rate can be influenced by density either
      negatively (e.g., competition effect) or positively (e.g., Allee effects). At the
      scale of an SSP, although positive density-dependent dispersal has been widely
      reported, an increasing number of studies have highlighted negative density
      dependent dispersal. While many studies have investigated the effects of density
      on population growth or on dispersal, few have simultaneously examined density
      dependent effects at the scale of both the local population and the entire SSP.
      In this study, we examine how density is related to demographic processes at both
      the pond level (survival and population growth) and the SSP level (between-pond
      dispersal) in a pond-breeding amphibian, the great crested newt (Triturus
      cristatus). The study was based on 20 years of individual capture-recapture (CR)
      data (from 1996 to 2015) gathered from an SSP made up of 12 experimental ponds
      ("patches"). We first used a CR multievent model to estimate both survival and
      dispersal rates in specific ponds as a function of distance between ponds. Then,
      using a second CR multievent model, we examined whether survival and recapture
      rates were influenced by population density in a pond. Lastly, we used state
      space time series models to investigate whether density affected population
      growth in each pond. Our results found a positive density-dependent effect on
      survival and a negative density-dependent effect on departure. In addition, the
      findings indicate that population growth was negatively related to density in all
      12 ponds. These results support the hypothesis that in SSPs, density may have
      multiple and contrasting effects on demographic parameters and growth rates
      within local populations as well as on dispersal. This study underlines the need
      to better understand how density dependence may influence potential trade-offs
      between life-history strategies and life-history stages.

PMID- 30280382
TI  - Exploring bone volume and skeletal weight in the Middle Pleistocene humans from
      the Sima de los Huesos site (Sierra de Atapuerca, Spain).
AB  - Body mass estimation in fossil human species is a crucial topic in
      paleoanthropology as it yields information about ecologically relevant
      characteristics. Nevertheless, variables crucial to body mass estimation such as
      bone volume and skeletal weight have never before been calculated in a fossil
      human species. The exceptional state of preservation of several fossil human long
      bones from the Sima de los Huesos (SH) Middle Pleistocene site, in the Sierra de
      Atapuerca, makes it possible to calculate for the first time the absolute bone
      volume in five complete long bones (two femora and three humeri) of a fossil
      human species, an approach not possible in fragmentary or poorly preserved
      fossils. We have relied on computed tomography scans and 3D reconstructions to
      calculate bone volume. A sample of 62 complete bones of robust recent humans was
      also used for comparative purposes. The male SH femora (weight-bearing bones) and
      humeri (non-weight-bearing bones) have, relative to their size, greater bone
      volume (volume of bone tissue over total bone volume) than the equivalent bones
      in our recent human sample. As mass is volume * density, and bone tissue density
      (as a material) is similar across mammals, we calculate bone mass, and our
      results show that the SH hominins had on average heavier long bones than extant
      humans of the same size. From the femoral weight at hand, we have estimated the
      total skeletal weight in two SH individuals, which is about 36% heavier than in
      the recent humans of the equivalent body size. Using different methods and
      skeletal variables, including skeletal weight, to estimate body mass in these two
      SH humans, we highlight the considerable differences in body mass estimates we
      obtained, and that the largest body mass estimate is the one based on the
      skeletal weight. Our results suggest that we cannot assume the same relative
      proportion of bone volume and bone and skeletal weight characterized the entire
      genus Homo. Given that skeletal weight has a significant influence on body mass,
      current body mass estimates of fossil Homo specimens could be systematically
      underestimated. Thus, the significantly larger bone volume and heavier bones,
      probably throughout the entire skeleton, of SH humans could have had consequences
      for many biological parameters in this Pleistocene population and considerable
      importance for studies focusing on adaptive and ecologically relevant
      characteristics. Although more recent human samples should be analyzed, in our
      view, the high skeletal robusticity of the SH sample, including larger bone
      volume and skeletal weight, is part of their adaptive body type selected for
      throughout the Pleistocene to support different mechanical and activity regimes
      and formed under tight genetic control, including control over bone formative and
      regulatory processes.

PMID- 30280383
TI  - Porphyromonas gingivalis triggers NLRP3-mediated inflammasome activation in
      macrophages in a bacterial gingipains-independent manner.
AB  - Porphyromonas gingivalis is a Gram-negative anaerobic bacterium that has been
      considered to be one of the bacteria associated with progression of human
      periodontitis. Subgingival biofilms formed by bacteria, including P. gingivalis,
      induce chronic inflammation, and activation of inflammasome in the gingival
      tissue. However, the mechanisms of P. gingivalis-triggering inflammasome
      activation and the role of bacteria-host interactions are controversial. In this
      study, we investigated the potential of P. gingivalis for triggering inflammasome
      activation in human cells and mouse models. We demonstrated that secreted or
      released factors from bacteria are involved in triggering NLR family, pyrin
      domain containing 3 protein (NLRP3) inflammasome in a gingipain-independent
      manner. Our data indicated that released active caspase-1 and mature IL-1beta are
      eliminated by proteolytic activity of secreted gingipains. These results
      elucidate the molecular bases for the mechanisms underlying P. gingivalis
      triggered inflammasome activation.

PMID- 30280384
TI  - Zebra diel migrations reduce encounter risk with lions at night.
AB  - Diel migrations (DM; back and forth diel movements along an ecological gradient)
      undertaken by prey to avoid predators during the day have been demonstrated in
      many taxa in aquatic ecosystems. In terrestrial ecosystems, prey often shift
      between various vegetation types whose cover determine their vulnerability (i.e.,
      likelihood of being killed when attacked). We conceptualized that in terrestrial
      ecosystems, DM could also occur and that the contribution of DM and shifts in
      vegetation cover use in reducing predation risk should depend upon the predator
      behaviour and the correlation between encounter risk and vulnerability across
      vegetation types. We further hypothesized that when the predator distribution is
      predictable, terrestrial prey could have evolved DM strategies taking them away
      from the predator when it is active or efficient. We investigated whether plains
      zebras Equus quagga perform DM in Hwange National Park (Zimbabwe). There, zebras
      can forage in large patches of open grasslands located near waterholes where they
      can also easily detect predators. However, they are there at high risk of
      encountering their main predator, lions Panthera leo, especially at night. We
      found out that zebras employ a DM anti-predator strategy. Zebras forage near
      waterholes during the day but move away from them at sunset, when lions become
      active. We demonstrated that this DM, occurring over a few kilometres,
      dramatically reduces their night-time risk of encountering lions, which generally
      remain close to waterholes. Zebra changes in night-time selection for vegetation
      cover types reduced their risk of encountering lions much less. This may arise
      from a trade-off between encounter risk and vulnerability across vegetation
      types, with zebras favouring low vulnerability once DM has reduced encounter
      risk. In summary, here we (a) quantify, in a terrestrial system, the effect of a
      predator-induced DM on the likelihood of encountering a predator and (b)
      distinguish the effects of the DM on encounter risk from those related to
      day/night changes in selection for vegetation types. We discuss how prey
      partition their risk between encounter risk and habitat-driven vulnerability and
      why it is likely critical to understand the emergence of anti-predator
      behavioural strategies.

PMID- 30280386
TI  - Urbanization-driven changes in web building and body size in an orb web spider.
AB  - In animals, behavioural responses may play an important role in determining
      population persistence in the face of environmental changes. Body size is a key
      trait central to many life-history traits and behaviours. Correlations with body
      size may constrain behavioural variation in response to environmental changes,
      especially when size itself is influenced by environmental conditions.
      Urbanization is an important human-induced rapid environmental change that
      imposes multiple selection pressures on both body size and (size-constrained)
      behaviour. How these combine to shape behavioural responses of urban-dwelling
      species is unclear. Using web building, an easily quantifiable behaviour linked
      to body size and the garden spider Araneus diadematus as a model, we evaluated
      direct behavioural responses to urbanization and body size constraints across a
      network of 63 selected populations differing in urbanization intensity. We
      additionally studied urbanization at two spatial scales to account for some
      environmental pressures varying across scales and to obtain first qualitative
      insights about the role of plasticity and genetic selection. Spiders were smaller
      in highly urbanized sites (local scale only), in line with expectations based on
      reduced prey biomass availability and the Urban Heat Island effect. Web surface
      and mesh width decreased with urbanization at the local scale, while web surface
      also increased with urbanization at the landscape scale. The latter two responses
      are expected to compensate, at least in part, for reduced prey biomass
      availability in cities. The use of multivariate mixed modelling reveals that
      although web traits and body size are correlated within populations, behavioural
      responses to urbanization do not appear to be constrained by size: there is no
      evidence of size-web correlations among populations or among landscapes, and web
      traits appear independent from each other. Our results demonstrate that responses
      in size-dependent behaviours may be decoupled from size changes, thereby allowing
      fitness maximization in novel environments. The spatial scale at which traits
      respond suggests contributions of both genetic adaptation (for web investment)
      and plasticity (for mesh width). Although fecundity decreased with local-scale
      urbanization, A. diadematus abundances were similar across urbanization
      gradients; behavioural responses thus appear overall successful at the population
      level.

PMID- 30280387
TI  - Explaining the variability in the response of annual eusocial insects to mass
      flowering events.
AB  - Empirical studies of annual eusocial insects in agricultural landscapes report
      contrasting findings with regard to colony responses to mass-flowering of crops
      such as oilseed rape. In particular, total sexual production is often unaffected
      by such events, whereas worker number responds with a prominent increase. To
      resolve these conflicting observations, we model-using an established approach
      the expected change in worker and sexual numbers in response to an increased
      worker productivity induced by mass-flowering events at different times of the
      season. We find that the predicted response pattern is mainly shaped by the
      degree to which individual worker productivity is reduced by an increasing number
      of workers in the colony. Different environmental conditions and colony
      characteristics result in different levels of interference of workers, for
      example, during foraging or nest construction. Reduction in individual
      productivity is low, when worker interference is negligible ("weak limitation")
      and high when an increasing number of workers substantially decreases per-capita
      efficiency ("strong limitation"). For weak limitation, any mass-flowering event
      that ends before the production of sexuals starts has a strong multiplicative
      impact on both worker and sexual numbers. The magnitude of the effect is quite
      independent of the precise timing of such an event. After the onset of sexual
      production, mass-flowering has a weaker effect, as the added resource supply is
      only linearly transferred into production of additional sexuals. For colonies
      under strong limitation, the predicted impact of mass-flowering events is
      generally weaker, especially on the production of sexuals, and the timing of mass
      flowering events becomes more influential: Production of sexuals profits more
      from late than from early mass-flowering events. Consequently, early mass
      flowering events are predicted to have a prominent effect on worker numbers but a
      negligible one on the output of sexuals. The model presented provides a
      mechanistic explanation of why increased worker abundances do not necessarily
      translate into increased production of sexuals. The model is also applicable to
      other eusocial insects such as paper wasps whenever brief pulses of massive
      resource availability shortly elevate resource intake rates above the "normal"
      levels.

PMID- 30280388
TI  - The hypolipidemic effects of Tamarindus indica fruit pulp extract in normal and
      diet-induced hypercholesterolemic hamsters are associated with altered levels of
      serum proteins.
AB  - The hypolipidemic effects of Tamarindus indica fruit pulp extract (Ti-FPE) have
      been earlier reported but the underlying molecular mechanisms are still
      uncertain. In this study, hamsters fed with Ti-FPE, both in the absence and
      presence of high-cholesterol diet, were shown to have significantly reduced
      levels of serum triglyceride, LDL-C and total cholesterol. The Ti-FPE-fed non
      hypercholesterolemic hamsters also showed significant enhanced levels of serum
      apolipoprotein A1, antithrombin III, transferrin and vitamin D binding protein.
      In diet-induced hypercholesterolemic hamsters, apolipoprotein A1, antithrombin
      III and transferrin, which were relatively low in levels, became significantly
      enhanced when the hamsters were fed with Ti-FPE. These Ti-FPE-fed
      hypercholesterolemic hamsters also showed significant higher levels of serum
      vitamin D binding protein. When the different treated groups of hamsters were
      analyzed for the levels of the four serum proteins by ELISA, similar altered
      abundance were detected. Ingenuity Pathway Analysis of the Ti-FPE modulated serum
      proteins singled out "Lipid metabolism, molecular transport, small molecule
      biochemistry" as the top network. Our results suggest that the hypolipidemic
      effects of Ti-FPE are associated with alterations of serum proteins that are
      known to be cardioprotective and involved in the metabolism of lipids. The MS
      data have been deposited to the ProteomeXchange Consortium with the dataset
      identifier PXD010232.

PMID- 30280389
TI  - Separation-free single-base extension assay with fluorescence resonance energy
      transfer for rapid and convenient determination of DNA methylation status at
      specific cytosine and guanine dinucleotide sites.
AB  - A separation-free single-base extension (SBE) assay utilizing fluorescence
      resonance energy transfer (FRET) was developed for rapid and convenient
      interrogation of DNA methylation status at specific cytosine and guanine
      dinucleotide sites. In this assay, the SBE was performed in a tube using an
      allele-specific oligonucleotide primer (i.e., extension primer) labeled with Cy3
      as a FRET donor fluorophore at the 5'-end, a nucleotide terminator
      (dideoxynucleotide triphosphate) labeled with Cy5 as a FRET acceptor, a PCR
      amplicon derived from bisulfite-converted genomic DNA, and a DNA polymerase. A
      single base-extended primer (i.e., SBE product) that was 5'-Cy3- and 3'-Cy5
      tagged was formed by incorporation of the Cy5-labeled terminator into the 3'-end
      of the extension primer, but only if the terminator added was complementary to
      the target nucleotide. The resulting SBE product brought the Cy3 donor and the
      Cy5 acceptor into close proximity. Illumination of the Cy3 donor resulted in
      successful FRET and excitation of the Cy5 acceptor, generating fluorescence
      emission from the acceptor. The capacity of the developed assay to discriminate
      as low as 10% methylation from a mixture of methylated and unmethylated DNA was
      demonstrated at multiple cytosine and guanine dinucleotide sites.

PMID- 30280390
TI  - First-time-in-human randomized clinical trial in healthy volunteers and
      haemodialysis patients with SNF472, a novel inhibitor of vascular calcification.
AB  - AIMS: SNF472 is a calcification inhibitor being developed for the treatment of
      cardiovascular calcification in haemodialysis (HD) and in calciphylaxis patients.
      This study investigated the safety, tolerability and pharmacokinetics (PK) of
      intravenous (IV) SNF472 in healthy volunteers (HV) and HD patients. METHODS: This
      is a first-time-in-human, double-blind, randomized, placebo-controlled Phase I
      study to assess the safety, tolerability and PK of SNF472 after ascending single
      IV doses in HV and a single IV dose in HD patients. A pharmacodynamic analysis
      was performed to assess the capability of IV SNF472 to inhibit hydroxyapatite
      formation. RESULTS: Twenty HV and eight HD patients were enrolled. The starting
      dose in HV was 0.5 mg kg-1 and the dose ascended to 12.5 mg kg-1 . The dose
      selected for HD patients was 9 mg kg-1 . Safety analyses support the safety and
      tolerability of IV SNF472 in HD patients and HV. Most treatment-emergent adverse
      events were mild in intensity. No clinically significant effects were observed on
      vital signs or laboratory tests. PK results were similar in HD patients and HV
      and indicate a lack of significant dialysability. Pharmacodynamic analyses
      demonstrated that SNF472 administration reduced hydroxyapatite crystallization
      potential in HD patients who received IV SNF472 9 mg kg-1 by 80.0 +/- 2.4% (mean
      +/- standard error of the mean, 95% CI, 75.3-84.8) compared to placebo (8.7 +/-
      21.0%, P < 0.001, 95% CI, -32.4 to 49.7). CONCLUSION: The results from this study
      showed acceptable safety and tolerability, and lack of significant dialysability
      of IV SNF472. It is a potential novel treatment for cardiovascular calcification
      in end-stage renal disease and calciphylaxis warranting further human studies.

PMID- 30280391
TI  - Monitoring Early Breast Cancer Response to Neoadjuvant Therapy Using H-Scan
      Ultrasound Imaging: Preliminary Preclinical Results.
AB  - OBJECTIVE: H-scan imaging is a new ultrasound technique used to visualize the
      relative size of acoustic scatterers. The purpose of this study was to evaluate
      the use of H-scan ultrasound imaging for monitoring early tumor response to
      neoadjuvant treatment using a preclinical breast cancer animal model. METHODS:
      Real-time H-scan ultrasound imaging was implemented on a programmable ultrasound
      scanner (Vantage 256; Verasonics Inc., Kirkland, WA) equipped with an L11-4v
      transducer. Bioluminescence and H-scan ultrasound was used to image luciferase
      positive breast cancer-bearing mice at baseline and at 24, 48, and 168 hours
      after administration of a single dose of neoadjuvant (paclitaxel) or sham
      treatment. Animals were euthanized at 48 or 168 hours, and tumors underwent
      histologic processing to identify cancer cell proliferation and apoptosis.
      RESULTS: Baseline H-scan ultrasound images of control and therapy group tumors
      were comparable, but the latter exhibited significant changes over the 7-day
      study (P < .05). At termination, there was a marked difference between the H-scan
      ultrasound images of control and treated tumors (P < .05). Specifically, H-scan
      ultrasound images of treated tumors were more blue in hue than images obtained
      from control tumors. There was a significant linear correlation between the
      predominance of the blue hue found in the H-scan ultrasound images and
      intratumoral apoptotic activity (R2  > 0.40, P < .04). CONCLUSION: Preliminary
      preclinical results suggest that H-scan ultrasound imaging is a new and promising
      tissue characterization modality. H-scan ultrasound imaging may provide
      prognostic value when monitoring early tumor response to neoadjuvant treatment.

PMID- 30280393
TI  - Factors associated with false-negative pathologic diagnosis of calciphylaxis.
AB  - BACKGROUND: Calciphylaxis is a rare, painful, and debilitating disorder of
      vascular calcification and skin necrosis that typically affects patients with
      advanced kidney disease. During our routine pathology practice, we noted several
      missed diagnoses on calciphylaxis consultation cases originating from outside
      institutions and sought to explore factors associated with false-negative
      pathologic diagnosis of calciphylaxis. METHODS: The pathology database of a large
      tertiary academic medical center was retrospectively searched for "calciphylaxis"
      in inside reports on outside surgical consultation cases between 2007 and 2017.
      Inside and outside pathology reports were compared and medical records were
      searched for calciphylaxis clinical diagnosis and risk factors. RESULTS: Twenty
      four calciphylaxis patients were identified, with median age of 63.5 years. Seven
      of 24 (29%) of specimens were inadequate (e.g., lack of subcutaneous adipose
      tissue for evaluation). Eight of 17 (47%) of adequate specimens had a first false
      negative pathologic diagnosis of calciphylaxis. Histochemical staining for
      calcium significantly correlated with true-positive diagnosis (93% vs 55%, P =
      0.004). Dermatopathology fellowship training significantly correlated with true
      positive diagnosis (82% vs 38%, P = 0.047). CONCLUSIONS: Adequate sampling,
      dermatopathology training, and use of histochemical stains to identify calcium
      associate with decreased false-negative rate for calciphylaxis diagnosis. These
      findings need further evaluation in larger prospective studies.

PMID- 30280392
TI  - Response to 'Comment on ''Massive' metformin overdose' by Chiew et al.'

PMID- 30280394
TI  - Public engagement lectures targeting prospective medical students: an opportunity
      for dermatology.

PMID- 30280395
TI  - Establishment of normative values for the fetal posterior fossa by magnetic
      resonance imaging.
AB  - OBJECTIVE: Suspected Dandy-Walker continuum anomalies constitute a significant
      percentage of prenatal cases evaluated by magnetic resonance imaging (MRI). To
      unify the description of posterior fossa malformations, we sought to establish
      objective measurements for the posterior fossa in normal fetuses between 18 and
      37 weeks gestation. METHODS: T2-weighted images of normal fetal brains in
      sagittal projection were obtained from fetal magnetic resonance (MR) studies of
      normal brains performed from 2009 to 2017.121 fetal brains were included in the
      analysis. Three radiologists reviewed images and recorded the following for each
      case: superior posterior fossa angle (SPFA), posterior fossa perimeter, and
      tegmento-vermian angle (TVA). RESULTS: For each feature, the mean of the
      measurements, the percentage of absolute difference of the reader measurement
      compared with mean measurement, and the interclass correlation (ICC) were
      calculated. Values are reported as mean +/- standard deviation. Perimeter
      increases linearly with age, whereas the SPFA and the TVA are independent of
      gestational age. For all included cases, the SPFA averaged 100.9 degrees  +/- 8
      degrees  and the TVA averaged 2.5 degrees  +/- 2.3 degrees . CONCLUSION: The
      superior posterior fossa angle, a novel measurement, and the posterior fossa
      perimeter can be used for establishing the expected size of the posterior fossa
      in second- and third-trimester fetuses by MRI.

PMID- 30280396
TI  - The Use of Transesophageal Echocardiography During Cardiac Arrest Resuscitation:
      A Literature Review.
AB  - We propose that transesophageal echocardiography (TEE) can be used to guide
      cardiac arrest resuscitation. We undertook a literature search (Medline and
      EMBase) to assess articles on that topic. Our search yielded 55 articles falling
      into 3 categories: TEE used in operating rooms, TEE used in emergency
      departments, and TEE used in other settings. In many cases, TEE changed the
      direction of the resuscitation; however, it is unclear whether TEE changed
      patient-oriented outcomes, such as neurologically intact survival. Few adverse
      events related to TEE have been documented. There is growing evidence that
      physicians can learn to use TEE during resuscitations and apply the findings to
      clinical decisions.

PMID- 30280397
TI  - Wrist Flexion Exercise Increases the Width of the Medial Elbow Joint Space During
      a Valgus Stress Test.
AB  - OBJECTIVES: The medial elbow is stabilized during valgus loading by the ulnar
      collateral ligament, the flexor pronator mass (FPM), and the radial head.
      Impairment of the FPM can occur as a result of repeated wrist flexion activity.
      The purpose of this study was to determine the effect of repeated elbow flexion
      exercise on medial elbow stability. METHODS: Thirty volunteers were included in
      this study. Ultrasound images of the medial joint space of the nondominant elbow
      of the participants were collected during a valgus stress test. The images were
      collected before and immediately after a wrist flexion exercise protocol.
      RESULTS: The wrist flexion strength measure decreased (7.5%) after the exercise
      protocol (t = 3.840; P = .001). The medial elbow width increased between
      unstressed (mean +/- SD, 2.8 +/- 0.1 mm) and stressed (3.6 +/- 0.1 mm) conditions
      (P < .001). The stress-by-fatigue interaction was significant (P = .048). The
      medial elbow width increased after fatigue (0.9 +/- 0.09 mm) while remaining
      unchanged in the unstressed condition. CONCLUSIONS: This study found an effect of
      repeated wrist flexion exercise on decreasing the stability of the medial elbow.
      Future research needs to explore the mechanisms leading to the decrease in medial
      elbow stability and to identify the effect of FPM fatigue on the development of
      medial elbow pain associated with activities.

PMID- 30280399
TI  - Percutaneous Ultrasonic Tenotomy Reduces Insertional Achilles Tendinopathy Pain
      With High Patient Satisfaction and a Low Complication Rate.
AB  - Due to the novelty of percutaneous ultrasonic tenotomy, the risks and benefits of
      this minimally invasive procedure for insertional Achilles tendinopathy pain have
      only been examined in case studies and retrospective chart reviews for other
      diagnoses. This retrospective chart review over a 3.5-year period identified 34
      patients with insertional Achilles tendinopathy who had percutaneous ultrasonic
      tenotomy (mean age +/- SD, 52.2 +/- 11.6 years; mean body mass index, 32.9 +/-
      7.5 kg/m2 ; 62% female). This procedure reduced the rate of moderate/severe pain
      from 68% at baseline to 15% at the long-term follow-up and had a satisfaction
      rate of 70%. There was 1 minor complication out of 40 procedures in 34 patients.

PMID- 30280398
TI  - Comparison of free-energy methods using a tripeptide-water model system.
AB  - We investigate the ability of several free-energy calculation methods to combine
      two alchemical changes. We use Bennett acceptance ratio (BAR), thermodynamic
      integration (TI), extended TI (X-TI), and enveloping distribution sampling (EDS)
      to perturb a water molecule, which is restrained to an amino acid that is also
      being perturbed. In addition to these pairwise methods, we present two two
      dimensional approaches, EDS-TI and two-dimensional TI (2D-TI). We compare
      feasibility, efficiency and usability of these methods in regard to our simple
      model system, which mimics the displacement of a water molecule in the active
      site of a protein on residue mutation. The correct treatment of structural water
      has been shown to greatly aid binding affinity calculations in some cases that
      remained elusive otherwise. This is of broad interest in, for example, drug
      design, and we conclude that thus far, the pairwise method BAR and also the newer
      X-TI remain the most suitable methods to treat this problem as long as few end
      states are involved. (c) 2018 Wiley Periodicals, Inc.

PMID- 30280400
TI  - Real-time ultrasound elastography evaluation of achilles tendon properties in
      patients with mild hemiplegic stroke after rehabilitation training.
AB  - OBJECTIVE: This study aims to evaluate the Achilles tendon's properties after
      rehabilitation training in patients with stroke using real-time ultrasound
      elastography. METHODS: A total of 24 patients with mild hemiplegic stroke in the
      past 6 to 12 months and unilateral lower limb movement disorder were
      prospectively enrolled. All patients accepted 9-week rehabilitation training with
      the same schema. The 2-dimensional elastography and real-time elastography
      findings in the impaired and contralateral normal Achilles tendon were measured
      at pretraining and at 3, 6, and 9 weeks after training, which included tendon
      length, thickness, elasticity score (grade 1-3), and strain ratio of fat to
      tendon. The functional properties, which include the 10-meter walk test and timed
      up-and-go scores, were evaluated before and after the 9-week training. RESULTS:
      The impaired Achilles tendon had a longer length (P = .002), lower frequency of
      grade 1 (P = .012), and lower strain ratio (P = .009) than the contralateral
      tendon before training. The impaired tendons at the third, sixth, and ninth weeks
      after training were compared to ones before training, respectively, which
      revealed shorter length, increased frequency of grade 1, and increased strain
      ratio. The first statistically significant changes in the length were observed at
      the sixth week, while such changes in elasticity score and strain ratio were
      observed at the ninth week. CONCLUSIONS: Two-dimensional elastography and real
      time elastography can provide valuable imaging markers for quantitatively
      evaluating the Achilles tendon's properties after rehabilitation training in
      patients with stroke.

PMID- 30280401
TI  - Bedside Ultrasound Versus Chest Radiography for Detection of Pulmonary Edema: A
      Prospective Cohort Study.
AB  - OBJECTIVES: Chest radiography has been the preferred imaging study to assess
      pulmonary congestion. However, chest radiography interpretation is influenced by
      the level of expertise and high interobserver variability. Lung ultrasound (US)
      may produce more objective findings through evaluation of vertical comet tail
      artifacts known as B-lines, which are created by a decrease in the ratio of
      alveolar air to fluid pulmonary content. Few studies have directly compared chest
      radiography to bedside US against a reference standard for the diagnosis of
      pulmonary edema. This study compared the sensitivity and specificity of bedside
      US and chest radiography in diagnosing pulmonary edema. METHODS: This prospective
      observational cohort study involved adult patients presenting to the emergency
      department of an urban tertiary hospital with dyspnea. The primary outcome was
      the presence or absence of pulmonary edema, as indicated by B-lines on a bedside
      lung US examination or radiologist-interpreted chest radiography. Patients
      underwent a US examination within about 1 hour of chest radiography. The final
      diagnosis from the discharge summary served as the reference standard. RESULTS:
      Ninety-nine patients were enrolled; 32.3% had congestive heart failure, and 40.4%
      had chronic obstructive pulmonary disease. Bedside US showed significantly higher
      sensitivity (96%) compared to chest radiography (65%; P < .001). Of 18 patients
      with negative radiographic findings and a discharge diagnosis of pulmonary edema,
      16 (89%) had positive US findings (P < .001). CONCLUSIONS: Bedside US has the
      potential to identify pulmonary edema more accurately than chest radiography. As
      current practice within the United States uses chest radiography, reflecting
      American College of Cardiology Foundation/American Heart Association guidelines
      for management of heart failure, the results of this study warrant further
      evaluation.

PMID- 30280402
TI  - Prenatal Evaluation for Detection of Anorectal Atresia: Value of Ultrasound.
AB  - OBJECTIVES: To investigate the applicability and value of ultrasound (US) in the
      diagnosis of anorectal atresia. METHODS: Between January 2008 and January 2016,
      we prospectively evaluated 63,101 fetuses (gestational age, 20-38 weeks),
      including low- and high-risk populations using 2-dimensional US scans. An
      abnormal imaging finding was defined as an anal canal diameter of less than the
      95% confidence interval (small anal canal) of the normal range or the absence of
      an anal canal and rectum. Imaging findings were considered normal on detection of
      an anal canal with a normal width and the absence of abnormalities. Prenatal
      imaging findings were confirmed by a postnatal or postmortem examination.
      RESULTS: Among the investigated fetuses, 28 showed evidence of anorectal atresia
      on US scans, and 22 of those with anorectal atresia had additional anomalies. Six
      cases of isolated anorectal atresia were successfully detected during the
      preclusive prenatal US scans. Four cases of a low imperforate anus (including 2
      covered anuses) yielded false-negative results, indicating a diagnostic rate of
      87.5% (28 of 32). The normal appearance of the fetal rectum and anal canal ruled
      out anorectal atresia in 30 fetuses with a dilated colon. Additionally, there
      were 3 false-positive cases, in which a narrow anal canal was observed.
      CONCLUSIONS: Identifying the abnormal appearance or absence of the fetal anal
      canal and rectum on preclusive US anomaly scans is useful for prenatal diagnosis
      or exclusion of anorectal atresia, which may help improve the detection of
      isolated anorectal atresia. Furthermore, a combined evaluation of the
      longitudinal and axial appearances of the fetal anal canal and rectum can improve
      diagnostic accuracy.

PMID- 30280403
TI  - Diving into chemical bonding: An immersive analysis of the electron charge
      rearrangement through virtual reality.
AB  - An integrated environment for the analysis of chemical bonding based on immersive
      virtual reality is presented. Using a multiscreen stereoscopic projection system,
      researchers are cast into the world of atoms and molecules, where they can
      visualize at a human scale the electron charge rearrangement (computed via state
      of-the-art quantum-chemical methods) occurring on bond formation throughout the
      molecular region. Thanks to specifically designed features, such a virtual
      laboratory couples the immediacy of an immersive experience with a powerful,
      recently developed method yielding quantitative, spatially detailed pictures of
      the several charge flows involved in the formation of a chemical bond. By means
      of two case studies on organometallic complexes, we show how familiar concepts in
      coordination chemistry, such as donation and back-donation charge flows, can be
      effectively identified and quantified to predict experimental observables. (c)
      2018 Wiley Periodicals, Inc.

PMID- 30280404
TI  - Comprehensive Evaluation of Fetal Cardiac Ventricular Widths and Ratios Using a
      24-Segment Speckle Tracking Technique.
AB  - INTRODUCTION: This study was conducted to evaluate the 24-segment transverse
      widths of the right and left ventricles distributed from the base to the apex of
      the ventricular chambers and compute the right ventricular (RV)/left ventricular
      (LV) ratios for each segment. METHODS: Two hundred control fetuses were examined
      between 20 and 40 weeks' gestation. Using offline speckle-tracking software, the
      24 end-diastolic transverse widths were computed and the RV/LV ratios were
      regressed against 7 independent variables related to the size, weight, and age of
      the fetuses. Five fetuses with coarctation of the aorta and 5 fetuses with
      pulmonary stenosis were examined to exemplify the utility of these measurements.
      FINDINGS: The 24-segment transverse widths were associated with changes in fetal
      size, weight, and age. Regression equations were developed to describe these
      changes with R2 values between .5 and .82. The measurements were normally
      distributed (Shapiro-Wilk > 0.5). The RV/LV ratio for the 24 segments did not
      strongly correlate (R2  = .001 to -.2) with fetal size, weight, or gestational
      age. Fetuses with coarctation of the aorta and pulmonary stenosis demonstrated
      characteristic changes in the 24-segment transverse widths and the RV/LV ratios
      in the basal (segments 1-8), mid (segments 9-16) and apical (segments 17-24)
      sections of the ventricles. CONCLUSIONS: The 24-segment transverse widths of the
      right and left ventricles and the RV/LV ratios provide a comprehensive method to
      examine the width of the ventricular chambers.

PMID- 30280405
TI  - High-Frequency Ultrasound Investigation of Port-Wine Stains: Hemodynamic Features
      Revealed By 10- and 22-MHz Transducers.
AB  - OBJECTIVES: The hemodynamics of the ultrasound (US) features of port-wine stains
      (PWSs) have not been reported. The purpose of this study was to evaluate the high
      frequency US findings of PWSs. METHODS: We retrospectively reviewed 98 PWS cases
      and categorized them into 4 groups based on clinical manifestations and
      pathologic findings (14 nodular, 28 thickened, 52 flattened, and 4 acquired). We
      evaluated the US findings with 10- and 22-MHz transducers. RESULTS: For nodular
      PWSs, the mean thickened skin +/- SD was 0.6 +/- 0.5 mm, and the nodule thickness
      was 5.7 +/- 3.3 mm; 63.6% of skin lesions showed vessel density of 2.16 +/-
      0.93/cm2 with venous flow of 4.6 +/- 1.1 cm/s, and all nodules showed vessel
      density of 6.14 +/- 1.92/cm2 with arterial and venous flow of 26.6 +/- 17.9 and
      9.9 +/- 5.1 cm/s, respectively. The thickened skin of the thickened type was 1.4
      +/- 2.7 mm; 76.5% of skin lesions showed vessel density of 3.81 +/- 1.98/cm2 with
      venous flow 4.6 +/- 2.1 cm/s. The thickened skin of 36 flattened lesions was 0.1
      +/- 0.1 mm; 91.7% of skin lesions showed vessel density of 1.08 +/- 0.28/cm2 .
      The thickened skin of 4 acquired lesions was 0.7 +/- 0.4 mm; 50% showed vessel
      density of 1.08 +/- 0.28/cm2 . The thickened skin and vessel density of nodular
      and thickened PWSs were thicker and higher than those of the flattened ones. The
      22-MHz transducer produced clearer contrast and higher vessel density than the 10
      MHz transducer. CONCLUSIONS: These results showed differences in US findings of
      PWSs, which may be useful for clinical diagnosis.

PMID- 30280406
TI  - Keratosis pilaris rubra with mucin deposition.
AB  - Keratosis pilaris (KP) is a benign cutaneous disorder characterized by
      folliculocentric hyperkeratotic papules most often occurring on the proximal
      extremities. Erythema is usually limited to perifollicular skin, but when
      keratosis pilaris presents on a background of confluent erythema, the term
      keratosis pilaris rubra (KPR) is used. The histological findings associated with
      KP have not been well described in the literature. Herein, we present a case of a
      14-year-old male with a 7-year history of erythema and follicular-based papules
      over his bilateral cheeks, consistent with KPR. Histological examination revealed
      abundant mucin, keratotic follicular plugging, and periadnexal lymphocytosis. Our
      novel finding of abundant dermal mucin expands the histopathologic description of
      KPR.

PMID- 30280407
TI  - Riluzole induces AR degradation via endoplasmic reticulum stress pathway in
      androgen-dependent and castration-resistant prostate cancer cells.
AB  - BACKGROUND: Prostate cancer (PCa) is diagnosed at the highest rate of all non
      cutaneous male cancers in the United States. The androgen-dependent (AD)
      transcription factor, androgen receptor (AR), drives PCa-but inhibiting AR or
      androgen biosynthesis induces remission for only a short time. At which point,
      patients acquire more aggressive castration-resistant (CR) disease with re
      activated AR-dependent signaling. To combat treatment resistance, down-regulating
      AR protein expression has been considered as a potential treatment strategy for
      CR-PCa. METHODS: AD- and CR-PCa cell lines were treated with the well-tolerated
      FDA-approved oral medicine, riluzole. Expression of full-length or wild-type AR
      (AR-FL) and constitutively active AR-splice variant 7 (AR-V7) was assessed by
      immunoblotting. AR-FL/AR-V7 activity was measured using qRT-PCR of AR-target
      genes. Cytoplasmic [Ca2+ ] levels were measured using a fluorescent Ca2+
      indicator microplate assay. Markers of the endoplasmic reticulum stress (ERS)
      pathway and autophagy were assessed by immunoblotting. Direct interaction between
      AR and selective autophagy receptor p62 was demonstrated by co
      immunoprecipitation. RESULTS: We demonstrate that riluzole downregulates AR-FL,
      mutant ARs, and AR-V7 proteins expression by protein degradation through ERS
      pathway and selective autophagy. Riluzole also significantly inhibited AR
      transcription activity by decreasing its target genes expression (PSA, TMPRSS2,
      and KLK2). CONCLUSIONS: We provide key mechanistic insights by which riluzole
      exerts its anti-tumorigenic effects and induces AR protein degradation via ERS
      pathways. Our findings support the potential utility of riluzole for treatment of
      PCa.

PMID- 30280408
TI  - Acitretin as a successful treatment for Hailey-Hailey disease.

PMID- 30280409
TI  - Homocysteine plasma levels in patients affected by hidradenitis suppurativa: an
      Italian experience.

PMID- 30280410
TI  - Risk factors for development of systemic lupus erythematosus in patients with
      cutaneous lupus: a retrospective review.

PMID- 30280411
TI  - Investigation of high-frequency hearing loss and outer hair cell function of the
      cochlea in patients with psoriasis: a case-control study.
AB  - The inner ear can be the target of autoimmune attacks, and sensorineural hearing
      loss can occur as a complication in various non-organ-specific autoimmune
      diseases. The aim of this study was to compare cochlear functions and hearing
      evaluation in patients with psoriasis and controls. In total, 29 patients with
      psoriasis and 30 healthy controls (HCs) were included in the study. Pure-tone
      audiometry at 250, 500, 1000, 2000, 4000, 8000, 10 000, 12 000, 14 000 and 16 000
      Hz was performed for patients as HCs, as were immittance measures including
      tympanometry, acoustic reflex and otoacoustic emission testing. There were
      statistically significant (P < 0.05) differences between patients and HCs for
      pure-tone thresholds at high frequencies, and for distortion product otoacoustic
      emission (DPOAE) responses and signal : noise ratio at all frequencies. In our
      study, based on DPOAE and audiological findings, there was damage to the outer
      hair cells of the cochlea, resulting in high-frequency hearing loss in patients
      with psoriasis.

PMID- 30280412
TI  - Sporadic pemphigus foliaceus and class II human leucocyte antigen allele
      associations in the white British and Indo-Asian populations in the UK.
AB  - BACKGROUND: Pemphigus foliaceus (PF) has both genetic and environmental
      susceptibility factors. Current data on human leucocyte antigen (HLA) in patients
      with sporadic PF are limited. AIM: To better define the distribution of HLA
      alleles in patients with PF in the UK. METHODS: We recruited 36 patients [26 of
      white British (WB) descent, 10 of Indo-Asian (IA) descent] with PF who were
      living in the UK and 159 ethnically matched normal controls, and analysed their
      class II HLA DRB1 and DQB1 allele distribution. RESULTS: There was an increased
      frequency of DRB1*1404 in association with DQB1*0503 in IA patients with PF. The
      DRB1*04 allele group as a whole had an increased frequency (P < 0.001) in the WB
      patient group compared with controls. The alleles contributing to this
      significance were DRB1*0401 (P = 0.03) and DRB1*0404 (P < 0.01). CONCLUSION: This
      is the largest HLA association study in sporadic PF from the UK to date. There
      appears to be a difference in PF susceptibility alleles between WB and IA
      patients, highlighting the importance of racial variation in genetic
      susceptibility to disease development.

PMID- 30280413
TI  - Penile necrobiosis lipoidica: case report and literature review.

PMID- 30280414
TI  - A rare case of a tattoo-induced morphoea reaction.

PMID- 30280415
TI  - Reflections on the Mental Health Parity and Addiction Equity Act After 10 Years.

PMID- 30280417
TI  - Skin cancer and welding.
AB  - Many workers in several different occupations can be exposed to ultraviolet
      radiation (UVR), which may increase their risk of developing skin cancer.
      Welding, an occupation employing an estimated 11 million people worldwide, is one
      such occupation. Welders are known to be exposed to the full spectrum of UVR from
      the welding arc and often experience burns and localized cutaneous erythema. In
      2017, UVR from welding was classified as carcinogenic to humans based on
      sufficient evidence of ocular melanoma in humans. It has been hypothesized that
      exposure to UVR from the welding arc also may increase the risk of skin cancer
      among workers in this occupation. This review summarizes the current literature
      on skin cancer risk in welders.

PMID- 30280418
TI  - Dental implants-associated release of titanium particles: A systematic review.
AB  - OBJECTIVES: The presence of titanium (Ti) particles around dental implants has
      been reported in the literature for decades. The prospective presence of Ti
      debris on soft tissues surrounding dental implants has not been systematically
      investigated and remains to be explored. Hence, this review aimed to evaluate the
      origin, presence, characteristics, and location of Ti particles in relation to
      dental implants. MATERIAL AND METHODS: Literature searches were conducted by two
      reviewers independently based on the PRISMA guidelines. The systematic review
      identified studies on Ti particles derived from dental implants. We evaluated
      several parameters, including anatomical location, and the suspected methods of
      Ti particles release. RESULTS: The search resulted in 141 articles, of which 26
      were eligible and included in the systematic review of the literature. The
      investigations reported Ti and metal-like particles in the soft (i.e., epithelial
      cells, connective tissue, and inflammatory cells) and hard (bone crest and bone
      marrow) tissues around the dental implants. Shape and size of the particles
      varied. The current literature reported a size range from 100 nm to 54 um
      identified by multiple particles identification methods. CONCLUSION: Ti particles
      surrounding peri-implant tissues are a common finding. Peri-implantitis sites
      presented a higher number of particles compared to healthy implants. The
      particles were mostly around the implants and inside epithelial cells, connective
      tissue, macrophages, and bone. Various mechanisms were described as causes of Ti
      release, including friction during implant insertion, corrosion of the implant
      surface, friction at the implant-abutment interface, implantoplasty, and several
      methods used for implant surface detoxification.

PMID- 30280419
TI  - Promoting medical student self-awareness through a challenging patient workshop.

PMID- 30280420
TI  - Cutaneous chromoblastomycosis effectively treated with local heat monotherapy.

PMID- 30280421
TI  - Cutaneous hyperpigmentation and familial gastrointestinal stromal tumour
      associated with KIT mutation.
AB  - Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours arising in the
      gastrointestinal tract. Early detection, before metastasis occurs, is important
      as complete surgical excision achieves cure. Approximately 85% of GISTs are
      associated with mutations in the KIT gene, and although the majority of GISTs are
      sporadic, familial GISTs have been identified. Several families with multiple
      GIST tumours have also been described with various cutaneous findings including
      hyperpigmentation, multiple lentigines, vitiligo and urticaria pigmentosa. We
      discuss a 6-year-old boy who presented with an unusual pattern of
      hyperpigmentation in association with a family history of GIST. A causative KIT
      mutation was identified in DNA from the pigmented skin and from the resected
      GIST, and the patient was referred to the Paediatric Gastroenterology department
      for GIST screening. The term 'GIST cutaneous hyperpigmentation disease' has been
      suggested previously for the association of familial GIST with cutaneous
      hyperpigmentation caused by a germline KIT mutation.

PMID- 30280422
TI  - Hypereosinophilia successfully treated with the novel antihistamine bilastine.

PMID- 30280416
TI  - Imaging of Motor Cortex Physiology in Parkinson's Disease.
AB  - There is abundant evidence that the pathophysiology of Parkinson's disease (PD)
      is not confined to the nigrostriatal dopaminergic pathway but propagates along
      the cortico-basal ganglia-thalamo-cortical neural network. A critical node in
      this functional circuit impacted by PD is the primary motor cortex (M1), which
      plays a key role in generating neural impulses that regulate movements. The past
      several decades have lay witness to numerous in vivo neuroimaging techniques that
      provide a window into the function and structure of M1. A consistent observation
      from numerous studies is that during voluntary movement, but also at rest, the
      functional activity of M1 is altered in PD relative to healthy individuals, and
      it relates to many of the motor signs. Although this abnormal functional activity
      can be partially restored with acute dopaminergic medication, it continues to
      deteriorate with disease progression and may predate structural degeneration of
      M1. The current review discusses the evidence that M1 is fundamental to the
      pathophysiology of PD, as measured by neuroimaging techniques such as positron
      emission tomography, single-photon emission computed tomography,
      electroencephalography, magnetoencephalography, and functional and structural
      MRI. Although novel treatments that target the cortex will not cure PD, they
      could significantly slow down and alter the progressive course of the disease and
      thus improve clinical care for this degenerative disease. (c) 2018 The Authors.
      Movement Disorders published by Wiley Periodicals, Inc. on behalf of
      International Parkinson and Movement Disorder Society.

PMID- 30280423
TI  - Differential expression of interferon-induced genes and other tissue-based
      biomarkers in acute graft-versus-host disease vs. lupus erythematosus in skin.
AB  - BACKGROUND: In both acute graft-versus-host disease (GVHD) and lupus
      erythematosus (LE), the patient's own tissues are subjected to immunological
      assault via complex mechanisms influenced by interferon (IFN) and other
      cytokines. Although not typically confused clinically, these entities have
      overlapping histopathological findings in the skin. AIM: To assess whether GVHD
      can be differentiated from LE using molecular methods on skin specimens. METHODS:
      We developed a quantitative reverse transcription PCR assay based on previously
      identified tissue-based biomarkers of cutaneous GVHD, and compared gene
      expression in GVHD with that in LE. RESULTS: Both entities showed robust
      expression of IFN-induced genes and of genes encoding proteins involved in
      antigen presentation, cell signalling and tissue repair. Levels of gene
      expression differed significantly in GVHD compared with LE, particularly those of
      IFN-induced genes such as MX1, OAS3, TAP1 and STAT3 (P < 0.01). Three logistic
      regression models could differentiate the two entities with a high degree of
      certainty (receiver operating characteristic area under the curve of 1.0).
      CONCLUSION: The study demonstrates the feasibility of distinguishing between
      microscopically similar inflammatory dermatoses using tissue-based molecular
      techniques.

PMID- 30280424
TI  - Efficacy of localized hand and foot phototherapy: a review of patients treated in
      a teaching hospital setting.

PMID- 30280425
TI  - Prevalence and Characteristics of Atypical Periprosthetic Femoral Fractures.
AB  - Bisphosphonate use has been associated with atypical femoral fractures (AFFs),
      defined by the American Society of Bone and Mineral Research (ASBMR) Task Force
      criteria, which currently exclude periprosthetic fractures. The objectives of
      this study were to establish the prevalence of atypical periprosthetic femoral
      fractures (APFFs) in patients with hip and knee arthroplasties and to determine
      the clinical and radiological risk factors associated with these fractures. We
      performed a retrospective radiological review of all femoral fractures between
      January 1, 2006, and March 31, 2015, in Quebec City, Canada. Patients who
      sustained a periprosthetic femoral fracture (PFF) were identified and included in
      this study. We used the ASBMR Task Force criteria to identify atypical fractures
      and establish their prevalence. Data from medical records and radiological
      assessments of the femoral anatomy, the characteristics of the fracture, and the
      positioning of the prosthesis were collected. The prevalence of APFFs among PFFs
      was 8.3% (11/133). A strong association with bisphosphonates (p = 0.007) was
      observed, as well as an increased risk of APFFs among alendronate users compared
      to risedronate users (p = 0.04). A transverse fracture (p < 0.0001), a periosteal
      thickening of the lateral cortex at the fracture (p < 0.0001), a unicortical
      fracture (p = 0.02), and prodromal symptoms (p = 0.03) were associated with
      APFFs. The type of implant, its positioning, and the femoral geometry did not
      appear to be risk factors for APFFs compared to PFFs. (c) 2018 American Society
      for Bone and Mineral Research.

PMID- 30280426
TI  - Systematic review and meta-analysis of prevalence of dermatological toxicities
      associated with vemurafenib treatment in patients with melanoma.
AB  - BACKGROUND: Vemurafenib has been linked to dermatological adverse events in
      patients with melanoma, including an increased risk of rash, cutaneous squamous
      cell carcinoma, photosensitivity reaction and keratoacanthoma. However, there has
      been no systematic attempt to assess the dermatological toxicity data of
      vemurafenib associated with melanoma treatment. AIM: To evaluate the point
      prevalence of dermatological toxicities associated with vemurafenib treatment in
      patients with melanoma. METHODS: Searches were conducted of the electronic
      databases PubMed and EMBASE and of conference abstracts published by the American
      Society of Clinical Oncology. Eligible studies included prospective clinical
      trials and expanded-access programmes (i.e. outside a clinical trial) of patients
      with melanoma assigned to vemurafenib treatment. Outcomes included prevalence of
      dermatological toxicities treated with vemurafenib. Statistical analyses were
      performed using the R2.8.1 meta package. RESULTS: In total, 11 studies comprising
      4197 patients were included in the meta-analysis. For patients assigned to
      vemurafenib, the overall prevalence of all-grade cutaneous squamous cell
      carcinoma (cSCC) was 18.00% (95% CI 12.00-26.00%), rash 45.00% (95% CI 34.00
      57.00%), photosensitivity reaction (PR) 30.00% (95% CI 23.00-38.00%),
      keratoacanthoma (KA) 10.00% (95% CI 6.00-15.00%) and hand-foot skin reaction
      (HFSR) 9.00% (95% CI 4.00-20.00%), while the prevalence of high-grade events was:
      cSCC 16.00% (95% CI 11.00-23.00%), rash 12.00% (95% CI 3.00-38.00%), PR 4% (95%
      CI 2.00-8.00%) and KA 6.00% (95% CI 5.00-7.00%). CONCLUSION: The most frequent
      dermatological toxicities associated with vemurafenib treatment in patients with
      melanoma were cSCC, rash, PR and KA. These data may be useful for estimation of
      the efficacy and safety of the drug during clinical treatment and for reducing
      the prevalence of adverse reactions to vemurafenib treatment in patients with
      melanoma.

PMID- 30280427
TI  - The nose as the predominant site for pemphigus foliaceous.

PMID- 30280428
TI  - Carcass yields, muscle amino acid and fatty acid profiles, and antioxidant
      indices of broilers supplemented with synbiotic and/or organic acids.
AB  - The objective of the current research was to explore the possible impacts of
      dietary supplementation with synbiotic and/or organic acids (OA) on the
      performance traits, carcass yields and muscle amino acid and fatty acid (FA)
      profiles of broilers. Randomly, a total of 160 day-old chicks (Ross 308) were
      assigned into four equal groups (40 birds each), with each group subdivided into
      eight replicates (five birds/pen). The control group (CON) fed the basal diet
      with no supplements, while diets of the treated groups were supplemented with OA
      (Sodium butyrate 40%; 1 g/kg), synbiotic (comprised Bacillus subtilis,
      Saccharomyces cerivisiae, Streptococcus faecium, Mannan-Oligosaccharides and beta
      Glucan; 1 g/kg) and equal mix of OA and synbiotic (2 g/kg). Broilers fed the
      diets supplemented with synbiotic or synbiotic plus OA produced a significantly
      higher feed utilization efficiency (p = 0.021) and carcass yields (p = 0.038)
      than the CON and OA-supplemented groups. The group fed the diet supplemented with
      the synbiotic showed lowered serum cholesterol (p = 0.049), triglycerides (p =
      0.001) and very low density lipoprotein (p = 0.032) when compared with the CON
      group. Regarding the polyunsaturated FA (PUFA) of breast muscles, synbiotic
      supplemented birds had significantly lower n-6:n-3 ratio (p = 0.047), however, a
      greater hypocholesterolaemic to hypercholesterolaemic FA (H/H) ratio was reported
      when compared with the CON group (p = 0.002). Among the essential amino acids,
      the contents of leucine and methionine in the breast (p = 0.032 and 0.007
      respectively) and thigh (p = 0.023 and 0.003 respectively) muscles were greater
      in the synbiotic-supplemented birds compared with the CON group. In conclusion,
      the synbiotic-supplemented diet improved the PUFA:SFA, n-6:n-3 and H/H ratios by
      altering the FA composition of broiler muscles, which are important with regards
      to human health.

PMID- 30280429
TI  - Contribution of different rumen microbial groups to gas, short-chain fatty acid
      and ammonium production from different diets-an approach in an in vitro
      fermentation system.
AB  - In this study, the relative contribution of different microbial groups to ruminal
      metabolism was investigated for different diets. The rumen microbial cultures
      included whole rumen fluid, fungi + protozoa, bacteria + protozoa, protozoa and
      bacteria + fungi and were established by physical and chemical methods. Gas
      production, short-chain fatty acid (SCFA) and ammonium production were measured
      at 24 hr in in vitro incubations using the Hohenheim gas test (HGT) procedure.
      Seven donor animal diets with different concentrate-to-roughage ratios (C:R:
      10:90, 30:70, 50:50, 70:30, 70:30BC (BC = NaHCO3 ), 90:10 and 90:10BC) and five
      HGT diets (C:R: 10:90, 30:70, 50:50, 70:30 and 90:10) were formulated.
      Incubations in the HGT were always based on inoculum from sheep diets with the
      respective C:R ratio. Gas and ammonium production increased (p < 0.001) as a
      result of a gradual increase in concentrate proportion of the diets. In general,
      SCFA production followed the same trend. Whole rumen fluid and bacteria + fungi
      produced approximately 50% higher gas volume than protozoa and fungi + protozoa
      fractions, whereas gas production with bacteria + protozoa was at an intermediate
      level. Coculture of protozoa either with bacteria or with fungi produced more
      ammonium. Populations without bacteria were characterized by a particularly high
      acetate/propionate ratio. Although an interaction between microbial group and
      diet was observed for several variables, no clear direction could be established.
      Manipulating rumen fluid by selectively suppressing specific rumen microbial
      groups may be a helpful tool in elucidating their role in nutrient degradation
      and turnover in vitro.

PMID- 30280430
TI  - Fast-Charging and High Volumetric Capacity Anode Based on Co3 O4 /CuO@TiO2
      Composites for Lithium-Ion Batteries.
AB  - This paper presents an investigation of anodic TiO2 nanotube arrays (TNAs), with
      a Co3 O4 /CuO coating, for lithium-ion batteries (LIBs). The coated TNAs are
      investigated using various analytical techniques, with the results clearly
      suggesting that the molar ratio of Co3 O4 /CuO in the TiO2 nanotubes
      substantially influences its battery performance. In particular, a cobalt/copper
      molar ratio of 2:1 on the TNAs (Co2 Cu1 @TNAs) features the best LIBs anode
      performance, exhibiting high reversible capacity and enhanced cycling stability.
      Noticeably, Co2 Cu1 @TNAs achieve excellent rate capability even after quite a
      high current density of 20.0 A g-1 (~25 C, where C corresponds to complete
      discharge in 1 h) and superior volumetric reversible capacity of ~3330 mA h-1  cm
      3 . This value is approximately seven times higher than those of a graphite-based
      anode. This outstanding performance is attributed to the synergistic effects of
      Co2 Cu1 @TNAs: 1) the structural advantage of TNAs, with their large amount of
      free space to accommodate the large volume expansion during Li+
      insertion/extraction and 2) the optimized ratio of Co3 O4 and CuO in the
      composite for improved capacity. In addition, no binder or conductive agent is
      used, which is partly responsible for the overall improved volumetric capacity
      and electrochemical performance.

PMID- 30280431
TI  - Synthesis of Biomass-Derived Carbon Induced by Cellular Respiration in Yeast for
      Supercapacitor Applications.
AB  - Because activated carbon is extensively used in supercapacitors, optimization of
      its precursors and synthetic strategies are crucial. Inspired by the rich sugar
      content of banana peel waste, which can be transformed through the respiration of
      yeast into alcohol with the release of CO2 , we developed an environmentally
      benign and highly efficient process for the production of renewable heteroatom
      doped hierarchical porous carbon materials (yeast-treated banana-peel-based
      carbon, denoted as YBP) without any additional templates or activation agents.
      The resulting biologically activated carbon was characterized by near-edge X-ray
      absorption fine-structure spectroscopy, X-ray photoelectron spectroscopy, and
      other physical methods. The biologically activated carbon achieved a maximum
      gravimetric specific capacitance of 476 F g-1 in 1 m H2 SO4 electrolyte.
      Remarkably, with a moderate specific surface area of 1084 m2  g-1 , the as
      obtained activated carbon was found to have a high packing density. With enriched
      pseudocapacitance sites, the YBP symmetric supercapacitor has a high volumetric
      specific capacitance and energy density (maximum values of 264 F cm-3 and 23.5 Wh
      L-1 , respectively). The supercapacitor showed superior cyclic stability, with 94
      % capacitance retention for voltage values up to 1.6 V after 10 000 cycles, which
      confirmed the promising application of this supercapacitor in miniature
      electronic devices.

PMID- 30280432
TI  - Sleeping beauty transposon-mediated poly(A)-trapping and insertion mutagenesis in
      mouse embryonic stem cells.
AB  - Saturation mutagenesis of all endogenous genes within the mouse genome remains a
      challenging task, although a plenty of gene-editing approaches are available for
      this purpose. Here, a poly(A)-trap vector was generated for insertion mutagenesis
      in mouse embryonic stem (mES) cells. This vector contains an expression cassette
      of neomycin (Neo)-resistant gene lacking a poly(A) signal and flanked by two
      inverted terminal repeats of the Sleeping Beauty (SB) transposon. The whole
      poly(A)-trap cassette can transpose into target TA dinucleotides, properly splice
      with endogenous genes and effectively interrupt the transcription of trapped
      genes in mES cells after transient induction of SB expression by doxycycline
      (DOX)-treatment at 1 MUg/ml, leading to the formation of multiple geneticin
      (G418)-resistant cell clones. In the first round of mutation screening, we
      identified six transposition events from 23 cell clones, including four inserted
      into an endogenous gene and two landed between endogenous genes. The abilities of
      self-renewal, totipotency, genetic stability and differentiation of syngap1+/-
      cells were not affected by DOX-treatment and G418-selection. These findings
      suggest that this SB transposon-mediated poly(A)-trap vector can be used as an
      alternative tool for a large-scale screening of mES cells with a gene mutation
      and for further generation of mutant mouse strains. Environ. Mol. Mutagen. 59:687
      697, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30280433
TI  - Medium-chain glycerides affect gut morphology, immune- and goblet cells in post
      weaning piglets: In vitro fatty acid screening with Escherichia coli and in vivo
      consolidation with LPS challenge.
AB  - The influence of medium-chain glycerides on performance and gastrointestinal well
      being in weaning piglets was assessed. First, caproic (C6), caprylic (C8) and
      capric (C10) acid activity against Escherichia coli was screened in vitro. Pig
      flora of the whole small intestine was used as inoculum. Seven in vitro
      incubations were done in duplicate at pH = 3 and 5: C10 (15 mM), C8 (12 mM), C6
      (15, 12, 10 mM), a non-incubated-negative control and incubated negative control.
      Culture suspensions were plated on E. coli-selective agar. Controls showed
      bacterial growth. C6 and C8 showed no growth at both pH-values, where C10 showed
      growth at pH = 5. Secondly, an in vivo study was done with 80 weaned piglets over
      42 days, housed in pens of eight animals (five pens/treatment), fed a basal diet
      containing broken rice/soya bean meal/fish meal and supplemented with C6 and C8
      in medium-chain glyceride form (MCT6/8, 0.175%) or antibiotic growth promoter
      (AGP, 0.020%) (Kasetsart University, Thailand) serving as control. Feed intake,
      daily gain and feed-to-gain ratio did not differ between MCT6/8 and AGP. Per
      replicate, two random selected piglets were challenged intravenously with E. coli
      lipopolysaccharide (LPS) or saline solution (S) at Days 21 and 28. All challenged
      animals were sacrificed; blood and digestive tract samples (jejunum/ileum) were
      collected at Day 35. LPS challenge consistently reduced villus height and crypt
      depth for MCT6/8 and AGP. However, LPS-challenged piglets supplemented with
      MCT6/8 restored villus height, where AGP did not. MCT6/8 piglets had higher serum
      IgA, more jejunal IgA-positive plasma cells and goblet cells than AGP. At the
      ileal level, results were similar, though less pronounced. The present study
      offers new insight in the benefits of MCT6/8 over AGP in the post-weaning period.
      There is in vitro anti-microbial action of C6 and C8 on E. coli. In vivo, MCT6/8
      also has protective effects in the small intestine that may result in growth
      promotion.

PMID- 30280434
TI  - Application of Six Sigma for evaluating the analytical quality of tumor marker
      assays.
AB  - CONTEXT: The results of detection assays for the same specimen are usually quite
      different in different laboratories or when tested with different detection
      systems. OBJECTIVE: This study was designed to investigate the value of applying
      sigma metrics derived from different standards for allowable total error (TEa) in
      evaluating the analytical quality of tumor marker assays. METHODS: Assays were
      evaluated for these six tumor markers: total prostate-specific antigen (tPSA),
      carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 199
      (CA199), carbohydrate antigen 125 (CA125), and carbohydrate antigen 153 (CA153).
      Sigma values were calculated for two concentrations of quality control products
      to assess differences in quality of tumor marker assays. Improvement measures
      were recommended according to the quality goal index, and appropriate quality
      control rules were selected according to the sigma value. RESULTS: The sigma
      value was highest using the higher biological variation-derived "appropriate" TEa
      standard: it was sigma >=6 or higher in 16.7% of tumor markers. Sigma was below 6
      for all tumor markers using the other three TEa. CEA, AFP, CA199, CA125, and
      CA153 required improved precision. The marker tPSA required improve precision and
      accuracy. According to sigma values by using China's external quality assessment
      standards, CEA, AFP, CA125, and CA153 require 13s /22s /R4s /41s multirules for
      internal quality control, CA199 requires use of 13s /22s /R4s /41s /8x
      multirules, and tPSA requires maximum quality control rules. CONCLUSION: Six
      Sigma is useful for evaluating performance of tumor markers assays and has
      important application value in the quality control of these assays.

PMID- 30280435
TI  - Searching for solutions to the conflict over Europe's oldest forest.

PMID- 30280436
TI  - Experiences of coeliac disease in a changing gluten-free landscape.
AB  - BACKGROUND: Coeliac disease is an autoimmune disorder triggered by the ingestion
      of gluten. In recent years, there has been considerable increase in the
      availability of gluten-free products in North America. The present study
      investigated how the recent proliferation of the gluten-free industry has
      affected individuals living with coeliac disease, with a primary focus on their
      social lives and relationships. METHODS: Interpretive phenomenology was utilised
      for study design and analysis. Semi-structured interviews were conducted with 17
      adults diagnosed with coeliac disease in Calgary, Alberta. Interviews were audio
      recorded and then transcribed for analysis. RESULTS: People living with coeliac
      disease experience the growth of the gluten-free industry as a 'double-edged
      sword'. Although they are grateful for more palatable gluten-free options, they
      are increasingly faced with misunderstandings about the severity of coeliac
      disease as a result of many noncoeliac disease individuals subscribing to the
      gluten-free diet. This 'double-edged sword' made certain types of social
      situations more easily manageable (e.g. more gluten-free options available at
      restaurants), whereas others produced distress (e.g. increased risk of
      inadvertently consuming gluten). Participants also felt they may be perceived or
      even perceived themselves differently (e.g. felt high maintenance). To help
      mitigate these social ramifications of following the gluten-free diet,
      participants utilised various strategies. CONCLUSIONS: The sole medical
      recommendation of a gluten-free diet fails to acknowledge the ongoing
      difficulties those with coeliac disease can endure in the current gluten-free
      landscape. Recommendations beyond the gluten-free diet are advisable to alleviate
      many of the indirect burdens revealed in the present study.

PMID- 30280437
TI  - Determination of copper and lead in tequila by conventional matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry and partial least squares
      regression.
AB  - RATIONALE: Quantification of small molecules by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) is
      challenging yet attractive, due to micro-scale procedural simplicity, high
      throughput and lack of memory effects. Since these features are important while
      analyzing trace elements in quality control schemes, MALDI-TOFMS was used for the
      determination of copper (Cu) and lead (Pb) in tequila with quantification carried
      out by partial least squares regression (PLS2) and by univariate calibration
      (UC). METHODS: In the proposed procedure, Bi(III) was added as internal standard
      (IS), diethyldithiocarbamate complexes were formed (pH 7.4) and extracted into
      chloroform; after solvent evaporation and re-constitution in acetonitrile, the
      sample was co-crystallized with alpha-cyano-4-hydroxycinnamic acid on a steel
      target. From the acquired mass spectra, UC was performed using IS-normalized
      signals of the monoisotopic ions of analytes, and the m/z range 350-513 was used
      for PLS2. Accuracy was tested by recovery experiments and by inductively coupled
      plasma (ICP)-MS analysis. RESULTS: When compared with direct analyte signal
      measurements, application of IS yielded enhanced analytical performance using
      either UC or PLS2; the method quantification limits were: 11.1 MUg L-1 , 23.4 MUg
      L-1 for Cu and 89.8 MUg L-1 , 97.1 MUg L-1 for Pb, respectively. In tequila,
      MALDI-TOFMS and ICP-MS provided consistent results for Cu (165-2599 MUg L-1 ); Pb
      was not detected in any sample by MALDI-TOFMS, yet recoveries obtained after
      standard addition were indicative of acceptable accuracy (400 MUg L-1 Pb added;
      recoveries: 91.2-108% for UC and 98.8-120% for PLS2). CONCLUSIONS: New
      experimental evidence has been provided supporting the inclusion of trace metals
      quantification within a range of MALDI-TOFMS applications. Slightly better
      results were obtained for UC as compared with PLS2 yet both methods can be
      recommended for testing the compliance of Cu and Pb levels with Official Mexican
      Norm. Of note, while using PLS2, there is no need for signal integration nor for
      IS normalization.

PMID- 30280438
TI  - Stable isotope ratios of carbon, nitrogen and selenium concentration in the scalp
      hair of Crohn's disease patients who ingested the elemental diet, Elental(r).
AB  - RATIONALE: Elental(r) is an elemental diet widely used as a nutritional
      supplement for Crohn's disease (CD) patients in Japan. Elental(r) contains amino
      acids as N-sources and does not contain selenium (Se), and the delta13 C and
      delta15 N values of Elental(r) are markedly higher and lower, respectively, than
      those of normal diet. METHODS: We compared the delta13 C and delta15 N values and
      Se concentration in the scalp hair of CD patients with those of control subjects
      who ate a regular diet, and estimated the amount of Elental(r) ingested as a
      supplement. The delta13 C and delta15 N values and the Se concentration were
      quantified using IRMS and ICP-MS, respectively. RESULTS: An increase of
      Elental(r) ingestion increased the delta13 C value in the hair of CD patients
      (p<0.05), while it reduced the delta15 N value (p<0.05) and tended to reduce the
      Se concentration in female patients. CONCLUSIONS: The amount of Elental(r)
      ingested could be estimated by the delta13 C and delta15 N values in the hair of
      CD patients. Furthermore, the Se deficiency in female patients may be predicted
      from the delta13 C and delta15 N values.

PMID- 30280439
TI  - The role of the cerebellum in drug-cue associative memory: functional
      interactions with the medial prefrontal cortex.
AB  - Drug-induced Pavlovian memories are thought to be crucial for drug addiction
      because they guide behaviour towards environments with drug availability. Drug
      related memory depends on persistent changes in dopamine-glutamate interactions
      in the medial prefrontal cortex (mPFC), basolateral amygdala, nucleus accumbens
      core and hippocampus. Recent evidence from our laboratory indicated that the
      cerebellum is also a relevant node for drug-cue associations. In the present
      study, we tested the role that specific regions of the cerebellum and mPFC play
      in the acquisition of cocaine-induced preference conditioning. Quinolinic acid
      was used to manage a permanent deactivation of lobule VIII in the vermis prior to
      conditioning. Additionally, lidocaine was infused into the prelimbic and
      infralimbic (IL) cortices for reversible deactivation before every training
      session. The present findings show, for the first time, that the cerebellum and
      mPFC might act together in order to acquire drug-cue Pavlovian associations.
      Either a dorsal lesion in lobule VIII or an IL deactivation encouraged cocaine
      induced preference conditioning. Moreover, simultaneous IL-cerebellar
      deactivation prevented the effect of either of the separate deactivations.
      Therefore, similar to the IL cortex, neural activity in the cerebellum may be
      crucial for ensuring inhibitory control of the expression of cocaine-related
      memories.

PMID- 30280440
TI  - Gas-phase rearrangement reaction of Schiff-base-modified peptide ions.
AB  - RATIONALE: Schiff base modification of peptides has been shown to facilitate
      their primary structural characterization via tandem mass spectrometry. However,
      we have discovered a novel rearrangement reaction via ion trap collisional
      activation involving the imine of the Schiff base and one of several functional
      groups, particularly the side chains of the basic residues lysine, arginine, and
      histidine, in the peptide. METHODS: Gas-phase ion/ion reactions involving an
      aldehyde-containing reagent were used to generate Schiff-base-modified model
      peptides in a hybrid triple quadrupole/linear ion trap tandem mass spectrometer.
      Subsequent ion trap collisional activation was used to study the rearrangement
      reaction. RESULTS: Schiff-base-modified peptide ions were found to undergo a
      rearrangement reaction that was observed to be either a major or minor
      contributor to the product ion spectrum, depending upon a variety of factors that
      include, for example, ion polarity, identity of the nucleophile in the peptide
      (e.g., side chains of lysine, histidine, and arginine), and the position of the
      nucleophile relative to the imine. CONCLUSIONS: Relatively low-energy
      rearrangement reactions can occur in Schiff-base-modified peptide ions that
      involve the imine of the Schiff base and a nucleophile present in the
      polypeptide. While this rearrangement process does not appear to compromise the
      structural information that can be generated via collisional activation of Schiff
      base-modified peptide ions, it can siphon away signal from the structurally
      diagnostic processes in some instances.

PMID- 30280441
TI  - Commentary on Stanesby et al. (2018): The importance of social change and trends
      in understanding increases in women's drinking in post-WWII Australia.

PMID- 30280442
TI  - Synthesis of the Highly Branched Hexasaccharide Core of Chlorella Virus N-Linked
      Glycans.
AB  - Chlorella viruses produce N-linked glycoproteins with carbohydrate moieties that
      differ in structure from all other N-linked glycans. In addition, unlike most
      viruses, these organisms do not hijack the biosynthetic machinery of the host to
      make glycocoproteins; instead, they produce their own carbohydrate-processing
      enzymes. A better understanding of the function and assembly of these fascinating
      and structurally-unprecedented glycans requires access to probe molecules. This
      work describes the first synthesis of a chlorella virus N-linked glycan, a highly
      branched hexasaccharide that contains the pentasaccharide present in all of the
      >15 structures reported to date. The target molecule includes a glucosyl
      asparagine linkage and a "hyperbranched" fucose residue in which all of the
      hydroxyl groups are glycosylated. Both convergent and linear approaches were
      investigated with the latter being successful in providing the target in 16 steps
      and 13 % overall yield.

PMID- 30280443
TI  - A developmental cascade model for early adolescent-onset substance use: the role
      of early childhood stress.
AB  - BACKGROUNDS AND AIMS: Despite the link between stress and addictive behavior in
      adulthood, little is known about how early life stress in families predicts the
      early emergence of substance use in adolescence. This study tested a
      developmental cascade model, proposing that early stressful life events and
      negative parent-child interaction covary, and both disrupt the refinement of
      inhibitory control, which evolves into problem behavior in middle/late childhood
      and subsequent substance use exploration in early adolescence. METHODS: Data came
      from the Early Steps Multisite study, a community sample of at-risk families in
      the metropolitan US areas of Pittsburgh (Pennsylvania), Eugene (Oregon) and
      Charlottesville (Virginia) with children aged 2 years at the start of the study
      and 14 years at the last measurement (n = 364). Structural equation modeling was
      used to test the proposed model. RESULTS: Early stressful life events and
      negative parent-child interaction assessed at ages 2-5 were negatively related to
      inhibitory control at ages 7 and 8. Low levels of inhibitory control were
      prognostic of childhood problem behavior at ages 9 and 10. Finally, late
      childhood problem behavior was associated with substance use at age 14. Parental
      drug use was directly related to substance use at age 14. CONCLUSIONS: Early life
      stress may disrupt child inhibitory control, which can cascade into behavioral
      and peer problem behavior in childhood and, in turn, heighten the risk for early
      adolescent substance use.

PMID- 30280444
TI  - A new UHPLC-MS/MS method for the direct determination of strigolactones in root
      exudates and extracts.
AB  - INTRODUCTION: Strigolactones (SLs) are the most representative germination
      stimulants for seeds of root parasitic plants, and they show activity even at
      concentrations below 10-10  M. The low amounts of stimulants produced by the host
      and their rapid degradability make it crucial to develop analytical methods with
      very low limits of quantification. OBJECTIVE: To develop a sensitive and
      validated analytical method for the simultaneous quantification of seven SLs [7
      oxoorobanchyl acetate (1), solanacol (2), orobanchol (4), strigol (5), fabacyl
      acetate (6), orobanchyl acetate (7), and 5-deoxystrigol (8)]. METHODS: SLs were
      analysed using ultra-high performance liquid chromatography coupled to tandem
      mass spectrometry (UHPLC-MS/MS), with (+/-)-GR24 (3) employed as internal
      standard (IS). Validation was based on selectivity, linearity, precision of the
      peak areas (repeatability and intermediate precision), detection and
      quantification limits, and stability. RESULTS: A simple, rapid and reliable UHPLC
      MS/MS method has been validated for the routine analysis of seven SLs and has
      been successfully applied to quantify them in exudates and extracts from tomato
      roots (Solanum lycopersicum). The limits of quantifications range from 0.05 MUg/L
      for 5-deoxystrigol to 0.96 MUg/L for solanacol. CONCLUSION: The method provides a
      useful tool for research in all the fields related to SLs, both for studies
      related to their function as hormones, and signalling molecules in the
      rhizosphere, without sample preparation required for extracts and root exudates
      in less than 11 minutes.

PMID- 30280445
TI  - The mir-200 family regulates key pathogenic events in ascending aortas of
      individuals with bicuspid aortic valves.
AB  - BACKGROUND: An individual with a bicuspid aortic valve (BAV) runs a substantially
      higher risk of developing aneurysm in the ascending aorta compared to the normal
      population with tricuspid aortic valves (TAV). Aneurysm formation in patients
      with BAV and TAV is known to be distinct at the molecular level but the
      underlying mechanisms are undefined. Here, we investigated the still incompletely
      described role of microRNAs (miRNAs), important post-transcriptional regulators
      of gene expression, in such aortic disease of patients with BAV as compared with
      TAV. METHODS AND RESULTS: Using a system biology approach, based on data obtained
      from proteomic analysis of non-dilated aortas from BAV and TAV patients, we
      constructed a gene-interaction network of regulatory microRNAs associated with
      the observed differential protein signature. The miR-200 family was the highest
      ranked miRNA, hence potentially having the strongest effect on the signalling
      network associated with BAV. Further, qRT-PCR and ChIP analyses showed lower
      expression of miR-200c, higher expression of miR-200 target genes, ZEB1/ZEB2
      transcription factors, and higher chromatin occupancy of the miR-200c promoter by
      ZEB1/ZEB2 in BAV patients, indicating a miR-200c/ZEBs negative feedback loop and
      induction of endothelial/epithelial mesenchymal transition (EndMT/EMT).
      CONCLUSION: We propose that a miR-200-dependent process of EndMT/EMT is a
      plausible biological mechanism rendering the BAV ascending aorta more prone to
      aneurysm development. Although initially supported by a miR-200c/ZEB feedback
      loop, this process is most probably advanced by cooperation of other miRNAs.

PMID- 30280446
TI  - Oligonol, a low-molecular-weight polyphenol derived from lychee peel, attenuates
      diabetes-induced pancreatic damage by inhibiting inflammatory responses via
      oxidative stress-dependent mitogen-activated protein kinase/nuclear factor-kappa
      B signaling.
AB  - This study investigated the effects of oligonol, a low-molecular-polyphenol
      derived from lychee peel, against diabetes-induced pancreatic damage via
      oxidative stress-induced inflammation. Oligonol was orally administered at 10 or
      20 mg/kg body weight/day for 10 days to streptozotocin-induced diabetic rats, and
      the rats were compared with nondiabetic and diabetic control rats. The diabetic
      rats showed loss of body weight and increased pancreatic weight, and the oral
      administration of oligonol attenuated these parameters. Moreover, the
      administration of oligonol caused a significant decrease in the serum glucose
      level and a significant increase in the serum and pancreatic insulin and C
      peptide levels in the diabetic rats. Oligonol also significantly reduced the
      enhanced levels of reactive oxygen species and 2-thiobarbituric acid reactive
      substance, which are oxidative stress biomarkers, in the serum and pancreas.
      Oligonol treatment reduced the overexpression of phospho-p38, phospho-ERK1/2,
      phospho-inhibitor of nuclear factor-kappa B (NF-kappaB), NF-kappaBp65, and NF
      kappaBp65-induced inflammatory protein such as cyclooxygenase-2, inducible nitric
      oxide synthase, tumor necrosis factor-alpha, and interleukin-6. Furthermore,
      oligonol treatment led to significantly attenuated histological damage in the
      pancreas. On the basis of these results, we conclude that a plausible mechanism
      of oligonol's antidiabetic action may be its antioxidative stress-related anti
      inflammatory action.

PMID- 30280447
TI  - Characterisation and screening of antimicrobial essential oil components against
      clinically important antibiotic-resistant bacteria using thin layer
      chromatography-direct bioautography hyphenated with GC-MS, LC-MS and NMR.
AB  - INTRODUCTION: The antimicrobial activity of many essential oils (EOs) is well
      established, indicating that EOs may be a source of compounds for antimicrobial
      drug development. Thin layer chromatography-direct bioautography (TLC-DB) can
      quickly identify antimicrobial components in complex mixtures and can be applied
      to the screening of EOs for lead compounds. OBJECTIVES: This study aimed to
      identify antimicrobial components of oregano, rosewood and cumin EOs against
      antibiotic-sensitive and -resistant bacteria using TLC-DB and a multi-faceted
      approach of GC-MS, LC-MS and NMR techniques to characterise bioactive compounds.
      The study also aimed to quantify the antimicrobial activity of bioactive
      compounds in order to evaluate their potential for the development of therapies
      against antibiotic-resistant bacteria. MATERIALS AND METHODS: EOs were eluted on
      TLC plates and sprayed with a suspension of Staphylococcus aureus, Enterococcus
      faecium, Escherichia coli or Pseudomonas aeruginosa (antibiotic-sensitive and 
      resistant isolates). Zones of inhibition, visualised with iodonitrotetrazolium
      chloride, were subject to GC-MS, LC-MS and NMR to characterise the bioactive
      compounds. RESULTS: Seven compounds were identified from the three EOs using GC
      MS, while LC-MS and NMR failed to detect the presence of any further non-volatile
      or heat labile compounds. Carvacrol was most antimicrobial compound identified,
      with minimum inhibitory concentrations ranging 0.99-31.62 mM. CONCLUSION: The
      identified antimicrobial compounds present in oregano, rosewood and cumin EOs
      including carvacrol may be candidates for the development of novel antimicrobial
      therapies against antibiotic-resistant bacteria.

PMID- 30280448
TI  - Understanding an emerging treatment population: Protocol for and baseline
      characteristics of a prospective cohort of people receiving treatment for
      pharmaceutical opioid dependence.
AB  - INTRODUCTION AND AIMS: Despite large increases in pharmaceutical opioid
      dependence and related mortality, few studies have focused on the characteristics
      and treatment experiences of those with pharmaceutical opioid dependence. We
      describe the formation of a prospective cohort of people receiving treatment for
      pharmaceutical opioid dependence and describe their baseline characteristics.
      DESIGN AND METHODS: People who had entered treatment for pharmaceutical opioid
      dependence (n = 108) were recruited through drug treatment services in New South
      Wales, Australia. We describe baseline characteristics of those that commenced
      pharmaceutical opioids for pain or other reasons and conducted a thematic
      analysis of responses regarding their treatment experience. RESULTS: Mean age was
      41 years (SD 11), half were male (48%). Just over half reported lifetime heroin
      use (57%). Oxycodone (49%) and codeine (29%) were the most common opioids
      reported. Most (85%) reported past-year problematic pain, 38% reported chronic
      pain. Half (52%) reported moderate to severe depression symptoms. Most (66%)
      commenced opioids for pain, and this group were older, less likely to report a
      previous overdose and less likely to report use of illicit drugs compared to
      those commencing for other reasons. Five themes related to treatment
      expectations: (i) stigma; (ii) the restrictive nature of treatment; (iii)
      knowledge; (iv) pain; and (v) positive experience with buprenorphine. DISCUSSION
      AND CONCLUSIONS: This study describes the complexities in an important emerging
      treatment population of pharmaceutical opioid-dependent people. Findings
      highlights that addressing knowledge and perceptions around treatment may be
      critical to address the rising mortality associated with pharmaceutical opioid
      dependence.

PMID- 30280449
TI  - An inclusive, online Delphi process for setting targets for best practice
      implementation for spinal cord injury.
AB  - RATIONALE, AIMS, AND OBJECTIVES: The Spinal Cord Injury Knowledge Mobilization
      Network is a pan-Canadian community of practice composed of seven rehabilitation
      hospitals. The goal of this network is to utilize implementation science
      processes to facilitate the adoption of best practice in spinal cord injury (SCI)
      rehabilitation. In addition to selecting specific practices for implementation, a
      key aspect of effective implementation is the engagement of stakeholders in
      decision-making processes. To achieve this, the network utilized a Delphi process
      to reach consensus on two pressure ulcer prevention and management practices to
      be implemented in SCI inpatient rehabilitation. A diverse, multidisciplinary
      panel of clinicians, researchers, sponsoring agency representatives, and persons
      with SCI participated in this process. METHOD: An online Delphi process was
      conducted in order to prioritize pressure ulcer prevention and management best
      practice recommendations and performance indicators for implementation. The
      process was conducted in six stages: (1) steering committee selection; (2)
      identification and selection of evidence; (3) participant selection and
      recruitment; (4) survey development; (5) identification of voting criteria; and
      (6) five rounds of voting. RESULTS: The Delphi process resulted in the selection
      of two best practices: (1) comprehensive risk assessment and (2) education for
      pressure ulcer prevention and management in persons with SCI. CONCLUSIONS: In
      this Delphi process, a large expert panel achieved consensus on best practice
      recommendations and associated performance indicators for implementation. This
      process was undertaken as a first step towards optimization of service delivery
      and outcomes for persons with SCI across Canada.

PMID- 30280450
TI  - Case series and systematic review of acquired diaphragmatic hernia after liver
      transplantation.
AB  - BACKGROUND: ADH is a rare and potentially fatal complication following LT. In
      this study, a systematic review was completed to identify risk factors which may
      contribute to ADH. METHODS: Transplant databases at three LT programs were
      reviewed. Four pediatric and zero adult cases were identified. Next, a systematic
      review was completed. Fourteen studies describing 41 patients with ADH were
      identified. Patient demographics, transplant characteristics, and features of ADH
      diagnosis were examined. RESULTS: The majority (90.2%) of ADH were in children.
      In pediatric LT, 95.1% received a segmental allograft. ADH occurred in the right
      P diaphragm 92.7% of the time, and 87.8% were repaired primarily. Patient
      demographics, post-transplant complications, and immunosuppression regimens were
      broad and failed to predict ADH. Most patients presented with either respiratory
      or gastrointestinal symptoms. There were two pediatric deaths related to
      undiagnosed ADH. The combined worldwide incidence of ADH in pediatric LT is 1.5%
      (34/2319 patients). CONCLUSION: ADH is a rare complication post-LT that primarily
      occurs in pediatric recipients. When diagnosed early, ADH can be repaired
      primarily with good outcomes.

PMID- 30280451
TI  - Unravelling the role and mechanism of adipokine and gastrointestinal signals in
      animal models in the nonhomeostatic control of energy homeostasis: Implications
      for binge eating disorder.
AB  - Central and peripheral signals regulating energy homeostasis interact tightly
      with neuronal pathways to modulate the hedonic component of food intake.
      Dysregulation of these interactions could explain the development of binge eating
      disorder (BED) and/or obesity and the increasing incidence of food addiction. In
      this review, we have highlighted the crucial role of peripheral hormones, such as
      leptin and ghrelin, among others, in these nonhomeostatic pathways. We have also
      emphasised the relevance of central cannabinoid pathway and lateral hypothalamus,
      with orexin and melanin-concentrating hormone neurons, as the critical hub
      controlling motivation and reward. Throughout the manuscript, we have focused on
      mechanisms learned from animal models of BED/food addiction in order to
      understand how these peripheral signals can modulate the motivation to eat.
      Understanding these mechanisms could help us to develop new treatment options for
      BED and/or obesity.

PMID- 30280452
TI  - Patient-reported and morbidity-mortality endpoints: can one have the best of both
      worlds?

PMID- 30280454
TI  - Frailty in TOPCAT: a deep dive into the deficit index approach for defining
      frailty.

PMID- 30280453
TI  - Patient-reported health-related quality of life outcomes in supportive-care
      interventions for adults with brain tumors: A systematic review.
AB  - OBJECTIVES: The objectives of this systematic review were to (a) identify
      supportive-care (psychosocial/behavioral, pharmacological, complementary, or
      alternative) interventions that have been evaluated via randomized controlled
      trials (RCTs) to improve patient-reported health-related quality of life (HRQoL)
      among adults with brain tumors, (b) evaluate the quality of the intervention
      studies, and (c) evaluate if developed interventions have been efficacious at
      improving HRQoL, as compared with control conditions in RCTs. METHODS: This
      systematic review was conducted using preferred reporting items for systematic
      reviews and meta-analyses (PRISMA) guidelines. Four databases were searched for
      RCTs of supportive-care interventions for adults with brain tumors, primary or
      metastatic, that included a patient-reported HRQoL outcome. Quality of the
      included studies was assessed using the Effective Public Health Practice Project
      Quality Assessment Tool for Quantitative Studies. RESULTS: Ten RCTs involving 640
      patients with either a primary or metastatic brain tumor investigating supportive
      care interventions with a HRQoL outcome were identified. In terms of quality,
      three of the studies received a "strong" rating, three received a "moderate"
      rating, and four of the studies received a "weak" rating. Only two of the
      interventions (ie, a home-based psychosocial intervention and individualized
      acupuncture with standard rehabilitation) demonstrated improvements in HRQoL over
      control conditions. CONCLUSIONS: HRQoL is of the utmost importance when treating
      patients with brain tumors. Yet there is a notable paucity of research to inform
      clinical decisions and evidence-based practice. More high-quality studies of
      interventions aimed at improving HRQoL are needed.

PMID- 30280455
TI  - Novel technique for pediatric living donor liver transplantation in patients with
      portal vein obstruction: The "pullout technique".
AB  - PV hypoplasia may increase the risk of posttransplant complications, especially
      when it extends to near the SMV and SpV junction. We described our experience of
      10 pediatric cases of PV hypoplasia/thrombus in which the pullout technique was
      required for PV reconstruction. There were five male and five female patients.
      The median age was 9 months, and the median weight was 8.1 kg. The indications
      for the pullout technique were PV hypoplasia in seven patients and PV thrombus in
      3. The inflow sites of the enlarged LGV were as follows: the main PV trunk (n =
      2), the SMV and SpV junction (n = 4), and the SpV (n = 4). The posterior face of
      the pancreas was tunneled along the PV, and the PV was returned to its original
      position with or without the use of an interposed vein graft. The pullout
      technique created a good operative field, which allowed for the complete removal
      of the hypoplastic PV or thrombectomy with the safe use of various interposed
      vein grafts.

PMID- 30280456
TI  - Construction of a risk prediction model of vancomycin-associated nephrotoxicity
      to be used at the time of initial therapeutic drug monitoring: A data mining
      analysis using a decision tree model.
AB  - OBJECTIVES: In our previous study, we built a risk prediction model of vancomycin
      (VCM)-associated nephrotoxicity using decision tree (DT) analysis. However, this
      has several limitations in clinical applications. Our objective here was to
      construct a clinically applicable risk prediction model to be used at the time of
      initial therapeutic drug monitoring (TDM), in patients with uncomplicated
      infections. METHOD: A retrospective study was conducted at Hokkaido University
      Hospital. Subjects that had received VCM were extracted between November 2011 and
      April 2017. Nephrotoxicity was defined as an increase in serum creatinine of 0.5
      mg/dL or 50% or higher from baseline. The additional inclusion criteria in this
      study were as follows: (1) the target trough level of VCM was set to 10 to 15
      mg/L, and (2) the duration of therapy was 7 to 14 days. Patients were assumed to
      have uncomplicated infections. Risk factors for nephrotoxicity were evaluated,
      which could be extracted at the initial TDM. In the DT analysis, a chi-squared
      automatic interaction detection algorithm was constructed. RESULTS: A total of
      402 patients were enrolled, and 56 (13.9%) patients developed nephrotoxicity. In
      the DT analysis, concomitant medications (furosemide, piperacillin-tazobactam,
      and vasopressor drugs) and an initial VCM trough concentration >= 15.0 mg/L were
      extracted as predictive variables by which patients were divided into six
      subgroups. The incidence of nephrotoxicity was 5.2% to 70.0%, with subgroups
      classified as low to high risk of nephrotoxicity. The accuracy of DT model was
      favourable (87.1%). CONCLUSION: We propose that the DT model built in this study
      is applicable to clinical practice.

PMID- 30280457
TI  - Knowledge about risk factors for falls and practice about fall prevention in
      older adults among physiotherapists in Nigeria.
AB  - BACKGROUND AND OBJECTIVE: Falling is a major health concern that has contributed
      significantly to older people's injury and loss of life worldwide, warranting the
      development of fall-prevention strategies, the success of which has been
      attributed to the levels of knowledge and practice about fall prevention among
      physiotherapists and other health professionals. The objective of this study was
      to determine the self-reported levels of knowledge on risk factors of fall and
      practices about fall prevention in older adults among physiotherapists in
      Nigeria. METHODS: Physiotherapists (N = 237) recruited from the six geopolitical
      zones of Nigeria completed a three-part structured questionnaire that asked
      questions about risk factors for fall and common practices for fall prevention
      using a 5-point-rated Likert scale. Data were analysed using descriptive
      analysis, chi-square, and Kruskal-Wallis tests. RESULTS: Among physiotherapists
      in Nigeria, 89% rated their level of knowledge about preventing falls among older
      adults as high, and 64% of them rated their level of practice on this topic as
      high. Among the individual items that measured knowledge, 40% of the participants
      reported a moderate level of knowledge about multiple medications as a risk
      factor for falls. Fifty percent of the participants reported a low level of
      practice of referral to other health care professionals, whereas 40% and 41%
      reported a moderate level of practice on documenting risk factors and treatment
      plans, respectively. There was no association between age, gender, or years of
      practice with levels of knowledge or practice. CONCLUSION: This study suggests
      that physiotherapists in Nigeria have adequate knowledge and practice for fall
      prevention in older adults. However, there are potential gaps in knowledge of
      risk factors, documentation, and referrals to other professions that may be
      addressed through developing context-specific fall-prevention clinical guidelines
      for practice in Nigeria.

PMID- 30280458
TI  - Synthesis of the Campylobacter jejuni 81-176 Strain Capsular Polysaccharide
      Repeating Unit Reveals the Absolute Configuration of its O-Methyl Phosphoramidate
      Motif.
AB  - The O-methyl phosphoramidate (MeOPN) motif is a non-stoichiometric modification
      of capsular polysaccharides (CPS) in ~70 % of all Campylobacter jejuni strains.
      Infections by C. jejuni lead to food-borne illnesses and the CPS they produce are
      key virulence factors. The MeOPN phosphorus atom in these CPS is stereogenic and
      is found as a single stereoisomer. However, to date, the absolute stereochemistry
      at this atom has been undefined. We report the synthesis of the three repeating
      units found in C. jejuni 81-176 CPS; one of these possesses a MeOPN group. In the
      course of these studies we established that the stereochemistry of the phosphorus
      atom in this MeOPN group is R. These studies represent the first unequivocal
      proof of stereochemistry of this group in any C. jejuni CPS. The compounds
      produced are anticipated to be useful tools in investigations targeting the
      function and biosynthesis of this structurally-interesting modification, which so
      far has only been identified in campylobacter.

PMID- 30280459
TI  - Effect of selenium supplementation on changes in HbA1c: Results from a multiple
      dose, randomized controlled trial.
AB  - AIM: To investigate the effect of selenium supplementation at different dose
      levels on changes in HbA1c after 6 months and 2 years in a population of low
      selenium status. MATERIALS AND METHODS: The Denmark PRECISE study was a single
      centre, randomized, double-blinded, placebo-controlled, multi-arm, parallel
      clinical trial with four groups. In total, 491 volunteers aged 60 to 74 years
      were randomly assigned to treatment with 100, 200 or 300 MUg selenium/day as
      selenium-enriched yeast or placebo-yeast. HbA1c measurements were available for
      489 participants at baseline, 435 at 6 months, and 369 after 2 years of selenium
      supplementation. Analyses were performed by intention to treat. RESULTS: The mean
      (SD) age, plasma-selenium concentration, and blood HbA1c at baseline were 66.1
      (4.1) years, 86.5 (16.3) ng/g and 36.6 (7.0) mmol/mol, respectively. During the
      initial 6-month intervention period, mean HbA1c (95% CI) decreased by 1.5 (-2.8
      to -0.2) mmol/mol for 100 MUg/d of selenium supplementation and by 0.7 (-2.0 to
      0.6) mmol/mol for the 200 and 300 MUg/d groups compared with placebo (P = 0.16
      for homogeneity of changes across the four groups). After 2 years of selenium
      supplementation, HbA1c had decreased significantly in all treatment groups, with
      no difference between active treatment and placebo. CONCLUSIONS: Selenium
      supplementation in an elderly European population of low selenium status did not
      significantly affect HbA1c levels after 2 years. Our findings corroborate a
      possible U-shaped response of selenium supplementation on glucose metabolism.

PMID- 30280460
TI  - Molecular and pathophysiological links between heart failure with preserved
      ejection fraction and type 2 diabetes mellitus.

PMID- 30280461
TI  - Fibrosis-matched outcomes between chronic hepatitis B patients with drug-induced
      virological response and inactive carriers.
AB  - BACKGROUND & AIMS: We compared the risk of hepatocellular carcinoma (HCC)
      development between patients with chronic hepatitis B (CHB) who achieved
      virological response (VR; HBV-DNA < 2000 IU/mL) with nucleos(t)ide analogues
      (NUCs) treatment (NUC-VR group) and patients with inactive CHB phase (ICHBP
      group). METHODS: To adjust for imbalances between NUC-VR and ICHBP groups,
      propensity score matching (PSM) models with 1:1 ratios were performed. RESULTS:
      This study included 2032 patients (n = 1291 in NUC-VR group and n = 741 in ICHBP
      group). Before PSM, NUC-VR group was at higher risk of HCC development than ICHBP
      group at 7 years (9.4% in NUC-VR group vs 3.3% in ICHBP group; P < 0.001).
      However, after PSM, the cumulative HCC development rates at 7 years were similar
      in NUC-VR and ICHBP groups using the three PSM models [2.0% vs 4.3%, PSM model-1
      (612 pairs); 3.7% vs 4.4%, PSM model-2 (618 pairs); and 2.4% vs 4.3%, PSM model-3
      (610 pairs)] (all P > 0.05). CONCLUSIONS: After adjusting heavier hepatic
      fibrosis burden in NUC-VR group, overall clinical outcomes between 2 groups had
      become comparable. Therefore, if appropriate, NUCs to prevent viral replication
      and hepatic inflammation are required for achieving better prognosis.

PMID- 30280462
TI  - Risk factors of pre-hypertension and hypertension among non-pregnant women of
      reproductive age in northeastern Tanzania: a community based cross-sectional
      study.
AB  - OBJECTIVES: To determine risk factors of pre-hypertension and hypertension in a
      cohort of 1247 rural Tanzanian women before conception. METHODS: Demographic and
      socioeconomic data, anthropometric measurements, past medical and obstetric
      history and other risk factors for pre-hypertension and hypertension were
      collected using a structured questionnaire. Multiple logistic regression analysis
      was used to evaluate the associations between anthropometric indices and other
      risk factors of pre-hypertension and hypertension. The predictive power of
      different anthropometric indicators for identification of pre-hypertension and
      hypertension patients was determined by Receiver Operating Characteristic curves
      (ROC). RESULTS: The median (range) age was 28.0 (18-40) years. The age
      standardised prevalences of pre-hypertension and hypertension were 37.2 (95% CI
      34.0-40.6) and 8.5% (95%CI 6.7-10.8), respectively. Of hypertensive patients (n =
      98), only 20 (20.4%) were aware of their condition. In multivariate analysis,
      increasing age, obesity and haemoglobin levels were significantly associated with
      pre-hypertension and hypertension. CONCLUSION: Despite a low prevalence of
      hypertension, over one third of the women had pre-hypertension. This poses a
      great challenge ahead as pre-hypertensive women may progress into hypertension as
      they grow older without appropriate interventions. Obesity was the single most
      important modifiable risk factor for pre-hypertension and hypertension.

PMID- 30280464
TI  - Angiographic and clinical outcomes of antegrade versus retrograde techniques for
      chronic total occlusion revascularizations: Insights from the PRISON IV trial.
AB  - OBJECTIVES: Available data indicate mixed outcomes after using retrograde
      techniques for chronic total occlusion(CTO) recanalization, with generally higher
      need for repeat revascularization. Aim of this study is to analyze the
      angiographic and clinical outcome of patients treated with retrograde techniques
      in the PRISON-IV trial. METHODS AND RESULTS: This is a post-hoc sub-analysis from
      the randomized PRISON-IV trial. Briefly, 330 patients with a successfully
      recanalized CTO lesion were randomized 1:1 to receive either hybrid-SES or EES.
      The hybrid-SES failed to reach the non-inferiority primary endpoint of in-segment
      late lumen loss at 9-month angiography follow-up. In the present analysis, we
      divided the population according to the first technical approach, namely
      antegrade (n = 285) or retrograde approach (n = 45). Demographic characteristics
      were similar between the two groups, while angiographic features disclosed higher
      CTO lesion complexity in the group treated with retrograde techniques (J-CTO
      score: 1.8 +/- 1.1 vs 2.6 +/- 1.1, respectively, P < 0.001), with longer
      occlusions (17.6 +/- 10 mm vs 28.8 +/- 18.7 mm, P < 0.001) and longer stented
      segment (48.9 +/- 24.4 mm vs 73.1 +/- 33.2 mm, P < 0.001). Quantitative coronary
      analysis disclosed similar results at follow-up angiography, with a non
      significantly higher in-stent late-lumen loss in the retrograde group (0.08 +/-
      0.52 mm vs 0.18 +/- 0.56 mm, P = 0.32). Clinical follow-up at 12-months showed
      similar outcome, with a non-significantly higher target-lesions revascularization
      rate in the retrograde group (6% vs 11.1% respectively, P = 0.2). Significant
      improvements in angina functional class were observed in both groups.
      CONCLUSIONS: The present analysis supports the benefits of retrograde techniques
      in CTO revascularization, with non-significant differences in angiographic and
      clinical outcomes at late follow-up.

PMID- 30280463
TI  - Vitamin D insufficiency predicts mortality among older men, but not women: A
      nationwide retrospective cohort from Thailand.
AB  - AIM: Previous studies on the association between low vitamin D level and
      increased mortality mainly came from high-income countries. The primary objective
      of the present study was to examine the effect of sex on the association between
      25-hydroxyvitamin D2 and D3 and mortality among community-dwelling older people
      in Thailand. METHODS: A cohort of individuals aged >=60 years from the Thai 4th
      National Health Examination Survey carried out in 2008 were followed and linked
      to a vital registry in 2015. Data regarding comorbid diseases, physical activity
      and serum vitamin D were obtained at the baseline assessment. Factors associated
      with all-cause mortality were determined using Cox proportional hazards models.
      RESULTS: A total of 1268 participants with a median age of 74.0 years
      (interquartile range 67.0-81.0) were included. The prevalence of vitamin D
      insufficiency was 24.5% and 43.9% in men and women, respectively. Vitamin D
      insufficiency was significantly associated with all-cause mortality only among
      men (adjusted HR 1.77, 95% CI 1.25-2.51), but not women. Analysis of 25
      hydroxyvitamin D3 divided into tertiles also showed an association with an
      adjusted HR of 1.83 (95% CI 1.23-2.72) for the lowest tertile in men. Diabetes
      was an effect modifier for low serum vitamin D and male sex, with HR 3.34 (95% CI
      1.76-6.33, P < 0.001) in diabetic men with vitamin D insufficiency. CONCLUSIONS:
      Low serum vitamin D is an independent risk factor for increased mortality in
      community-dwelling Thai older men. Further randomized controlled study to
      investigate the benefit of vitamin D3 supplementation in older persons,
      particularly men, is warranted. Geriatr Gerontol Int 2018; **: **-**.

PMID- 30280465
TI  - Association between diabetic eye disease and other complications of diabetes:
      Implications for care. A systematic review.
AB  - The aim of this systematic review was to examine the associations between
      diabetic retinopathy (DR) and the common micro- and macrovascular complications
      of diabetes mellitus, and how these could potentially affect clinical practice. A
      structured search of the PubMed database identified studies of patients with
      diabetes that assessed the presence or development of DR in conjunction with
      other vascular complications of diabetes. From 70 included studies, we found that
      DR is consistently associated with other complications of diabetes, with the
      severity of DR linked to a higher risk of the presence of, or of developing,
      other micro- and macrovascular complications. In particular, DR increases the
      likelihood of having or developing nephropathy and is also a strong predictor of
      stroke and cardiovascular disease, and progression of DR significantly increases
      this risk. Proliferative DR is a strong risk factor for peripheral arterial
      disease, which carries a risk of lower extremity ulceration and amputation.
      Additionally, our findings suggest that a patient with DR has an overall worse
      prognosis than a patient without DR. In conclusion, this analysis highlights the
      need for a coordinated and collaborative approach to patient management. Given
      the widespread use of DR screening programmes that can be performed outside of an
      ophthalmology office, and the overall cost-effectiveness of DR screening, the
      presence and severity of DR can be a means of identifying patients at increased
      risk for micro- and macrovascular complications, enabling earlier detection,
      referral and intervention with the aim of reducing morbidity and mortality among
      patients with diabetes. Healthcare professionals involved in the management of
      diabetes should encourage regular DR screening.

PMID- 30280466
TI  - Real-world comparison of the new 34 mm self-expandable transcatheter aortic
      prosthesis Evolut R to its 31 mm core valve predecessor.
AB  - OBJECTIVES: The aim of the present study was to compare the incidence of
      periprocedural complications and short-term outcomes between the second
      generation recapturable 34 mm Evolut-R and its first-generation 31 mm
      predecessor. BACKGROUND: Although already in extensive clinical use in real world
      patients, the periprocedural complications and clinical outcomes of the new 34 mm
      device have not been investigated yet. METHODS: Consecutive patients who had
      undergone transcatheter aortic valve implantation in two centers with either a 31
      mm CoreValve or a 34 mm Evolut-R device were retrospectively studied.
      Periprocedural complications of malpositioning, valve-in-valve implantation,
      conversion to full sternotomy or percutaneous coronary intervention and vascular
      complications were compared between the two groups. Short-term outcomes at
      discharge were compared using Valve Academic Research Consortium (VARC-2)
      criteria. RESULTS: The study group included 106 patients (35 Evolut-R 34 mm; 71
      CoreValve 31 mm). Significantly lower rates of valve-in-valve implantation were
      demonstrated for the 34 mm group compared to the first-generation device (0% vs.
      11.9%, respectively, P = 0.036). All other periprocedural complications were
      similar between groups. At discharge, the rates of new pacemaker implantation
      (5.7% vs. 26.8%, P = 0.037) and bleeding complications (2.9% vs. 19.6%, P =
      0.025) were statistically significantly lower among the 34 mm group. With regards
      to VARC-2 defined combined endpoints, rates of early safety were significantly
      improved among the 34 mm group compared to 31 mm group (0% vs. 27.9%,
      respectively, P = 0.004). CONCLUSIONS: The recently introduced 34 mm Evolut-R
      seems to demonstrate an improved safety profile, as evidenced by the reduced
      bleeding rates, lower rates of valve-in-valve implantation and lower PPM rates
      compared to its 31 mm predecessor.

PMID- 30280467
TI  - Awareness of oral medicine among medical practitioners, evidence of the unbridged
      interdisciplinary gap.
AB  - RATIONALE, AIMS, AND OBJECTIVES: Inadequate awareness of oral health and related
      disciplines appears to be common among medical practitioners. This study was
      designed to evaluate the awareness of oral medicine (OM) specialty and its scope
      of practice among Jordanian medical practitioners and to outline potential
      strategies for improvement where appropriate. METHOD: A specially designed
      questionnaire was electronically distributed to Jordanian medical practitioners
      and thereafter via personal interviews to improve the response rate. The
      questionnaire comprised nine questions and covered demographical details and
      characteristics of participants, in addition to their awareness of OM and
      agreement to refer a group of common oral and dental conditions to OM
      specialists. Pearson Chi-square tests were used to examine the significance of
      association between the variables of respondents and awareness of OM.
      Significance level was set at P values < 0.05. RESULTS: A total of 1492
      respondents completed the questionnaire, of which 779 (52.2%) were aware of OM as
      an independent specialty. Age group, higher degrees in medicine, country of
      graduation, and the specialty type were significant determinants of OM awareness
      level. Oral ulceration and other mucosal pathology, including fungal infections,
      were the most likely conditions to be referred to OM specialists while
      participants had apparent problems separating the scope of practice of OM from
      other dental disciplines. CONCLUSION: This study provides evidence on the
      profound interdisciplinary gap between medicine and dentistry and highlights the
      importance of more focused education and training in oral health-related
      disciplines to be provided to clinicians and medical trainees as described.

PMID- 30280468
TI  - The efficacy of non-assisted reproductive technology treatment might be limited
      in infertile patients with advanced endometriosis in their 30s.
AB  - AIM: To determine the efficacious treatment for infertile couples, we assessed
      the impact of infertility factors including endometriosis on assisted
      reproductive technology (ART) and non-ART treatment, and the effect of age in
      infertility treatment outcomes was also investigated. METHODS: The medical
      records of 1864 females, infertile patients from January 2000 to December 2015 at
      our hospital, were retrospectively reviewed under the approval of the
      Institutional Review Board. We extracted 10 representative factors and calculated
      the cumulative live birth rate (CLBR) in these patients. Multivariate analysis of
      ART and non-ART treatment was performed to assess the impact of infertility
      factors, and the age-related decline in cumulative live birth rate was calculated
      by creating eight age-stratified subgroups. RESULTS: In total, 21.9% and 49.4% of
      the patients conceived after being treated with non-ART and ART, respectively.
      Multivariate analysis revealed that age > 35, advanced endometriosis defined by
      the revised American Society for Reproductive Medicine classification system
      stages III to IV, and the past history or current presence of uterine fibroid had
      significantly negative impact on the outcome of non-ART. Age stratification
      revealed that advanced endometriosis adversely affected the outcome of non-ART,
      especially for patients in their 30s. Assisted reproductive technology treatment
      for patients with advanced endometriosis was shown to be efficacious because the
      negative impact had been diminished. CONCLUSION: Considering that non-ART
      treatment had limited role in patients with advanced endometriosis, prompt
      initiation of ART in these patients aged as young as 30 years can be recommended
      to achieve conception.

PMID- 30280469
TI  - Role of contractile reserve as a predictor of mortality in low-flow, low-gradient
      severe aortic stenosis following transcatheter aortic valve replacement.
AB  - OBJECTIVES: The aim of this study was to determine the prognostic value of
      contractile reserve (CR) at baseline in patients with low-flow, low-gradient
      severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement
      (TAVR). BACKGROUND: Patients with severe AS, left ventricular dysfunction, and
      low transaortic gradient are at high risk for mortality during surgical aortic
      valve replacement (SAVR). Furthermore, patients without CR have been shown to
      have perioperative mortality comparable to that of patients treated medically for
      severe AS. METHODS: We retrospectively analyzed patients who underwent TAVR with
      a diagnosis of low-gradient severe AS (mean transvalvular aortic gradient < 40
      mmHg, LVEF < 50%, and AVA <= 1.0 cm2 or AVAi <= 0.6 cm2 ) and who had a pre-TAVR
      dobutamine stress echocardiogram (DSE). Patients were stratified by the presence
      or absence of CR, defined as an increase in stroke volume >= 20% during DSE.
      RESULTS: From 2008 to 2016, 61 patients with low-gradient severe AS underwent
      TAVR and had pre-TAVR DSE. CR was present in 31 patients (51%) and absent in 30
      (49%). There was no significant difference between the two groups in baseline
      demographics, medical history, access site, or types of valves. All-cause
      mortality was similar in both groups at 30 days (13% with CR vs 10% without CR, P
      = 1.00) and 1 year (29% with CR vs 33% without CR, HR 1.20, 95% CI 0.49-2.96, P =
      0.69). CONCLUSION: In patients with low-flow, low-gradient severe AS undergoing
      TAVR, the presence or absence of CR does not predict all-cause mortality at 30
      days or 1 year.

PMID- 30280471
TI  - Percutaneous closure of paravalvular leak after Cone repair for Ebstein's
      anomaly.
AB  - We report the use of an Amplatzer Vascular plug for percutaneous closure of a
      paravalvular leak after Cone repair in a 5-year-old boy with Ebstein's anomaly. A
      paravalvular leak of the tricuspid valve developed gradually after Cone repair
      surgery. The combination of fluoroscopy, transesophageal and transthoracic
      imaging during general anesthesia was necessary for correct and safe positioning
      of the device by percutaneous approach. The results were promising.

PMID- 30280470
TI  - A comparative study of ammonia transport across ruminal epithelia from Bos
      indicus crossbreds versus Bos taurus.
AB  - Absorption of ammonia from the rumen of cattle decreases nitrogen availability
      for fermentational protein synthesis, leading to increased competition of cattle
      with humans for protein and enhancing the release of toxic nitrogenous compounds
      into the environment. Given that differences in feeding and breeding might induce
      differences in ruminal ammonia transport, we compared electrophysiological,
      histological, and molecular biological characteristics of ruminal epithelia of
      Bos indicus crossbreds (Sahiwal-Mix, SWM) with those of Bos taurus (Holstein
      Friesian, HF). As in HF, the stratified cornified epithelium of SWM expressed
      claudin 1 and 4. Measurements of ammonia flux (HF) and serosal pH (both breeds)
      suggested that at a mucosal pH of 6.4, net transport primarily occurred as NH4 +
      . As shown previously for HF, NH4 + induced a concentration-dependent rise in
      short circuit current (Isc ) in SWM that could be further stimulated by the TRP
      channel agonist menthol. Relative mRNA expression levels for TRPV3, TRPV4, TRPM6,
      and TRPM7 were significantly lower in SWM than in HF, with TRPA1 expression near
      the limit of detection. We conclude that uptake of ammonia from the rumen of both
      breeds occurs electrogenically as NH4 + with functional and molecular biological
      evidence pointing towards involvement of TRPV3 and TRPV4.

PMID- 30280472
TI  - Predictors and etiologies of 30-day readmissions in patients with non-ST
      elevation acute coronary syndrome.
AB  - BACKGROUND: Despite improvements in acute care and survival after non-ST
      elevation acute coronary syndrome (NSTE-ACS) hospitalization, early readmissions
      remain common, and have significant clinical and financial impact. OBJECTIVES:
      Determine the predictors and etiologies of 30-day readmissions in NSTE-ACS.
      METHOD: The study cohort was derived from the National Readmission Database 2014
      identifying patients with a primary diagnosis of NSTE-ACS using ICD9 code.
      RESULTS: We identified a total of 300,269 patients admitted with NSTE-ACS; 13.4%
      were readmitted within 30-day. The most common cause of readmission was heart
      failure (HF) (15.6%), followed by a recurrent myocardial infarction (MI) (10%).
      Predictors of increased readmissions were age >= 75 years (OR: 1.34, 95% CI: 1.30
      1.39), female gender (OR 1.12, 95% CI 1.09-1.16), a Charlson Comorbidity Index
      (CCI) >3 (OR 2.11, 95% CI: 2.04-2.18), ESRD (OR 2.01, 95% CI 1.89-2.14), CKD (OR:
      1.58, 95% CI: 1.51-1.64), length of stay >=5 days (OR: 1.51, 95% CI 1.46-1.56)
      and adverse events during the index admission such as AKI (OR:1.31, 95% CI: 1.25
      1.36), major bleeding (OR:1.20, 95% CI: 1.12-1.24); whereas admission to a
      teaching hospital (OR 0.92, 95% CI 0.89-0.95) and PCI (OR 0.70, 95% CI 0.67-0.72)
      were associated with less likelihood of 30-day readmission. CONCLUSION:
      Readmission rate at 30-days is high among NSTE-ACS patients and the most common
      readmission etiologies are HF and recurrent MI. A CCI more than 3 and ESRD were
      the most significant predictors for readmission; patients undergoing PCI had less
      odds of readmission.

PMID- 30280473
TI  - Skin surface lipid differences in sensitive skin caused by psychological stress
      and distinguished by support vector machine.
AB  - BACKGROUND: Sensitive skin refers to skin that tends to be highly responsive to
      stimuli such as physical, chemical, and psychological. Psychological factors play
      an important role in the pathology of sensitive skin. OBJECTIVE: This study
      investigated lipid difference between sensitive skin caused by psychological
      stress and normal skin, followed by construction of a support vector machine
      (SVM). METHODS: A noninvasive method was used to collect lipid samples from the
      skin surface. Ultra-performance liquid chromatography quadrupole time of flight
      mass spectrometry (UPLC-Q-TOF-MS) technique and partial least squares
      discriminant analysis (PLS-DA) was used to screen for differential lipids. A
      correlation analysis was performed on differential lipids, and a support vector
      model was established based on the differential lipids. RESULTS: Twelve
      differential lipids were obtained, and the most differentiating species were
      triacylglycerols (TGs), followed by monounsaturated fatty acids (MUFAs),
      saturated fatty acids (SFAs), diacylglycerols (DGs), and 6-hydroxysphingosine
      levels. Triglyceride, SFA, and MUFA species showed a high correlation, and the
      support vector machine (SVM) differentiation model based on differential lipids
      had a 100% accuracy rate. CONCLUSION: Psychological stress may cause damage to
      the permeability and antimicrobial barriers of the skin, thereby resulting in
      sensitive skin. Differentiation models based on SVMs have good prospects for
      distinguishing sensitive skin caused by psychological stress.

PMID- 30280474
TI  - Low-fluence Q-switched Nd:YAG laser for the treatment of melasma in Asian
      patients.
AB  - BACKGROUND: Melasma is a common acquired facial pigmentary disorder that is
      resistant to various modalities of treatment. Recently, the low-fluence 1064-nm Q
      switched neodymium-doped yttrium aluminum garnet laser (QSNY) has emerged as the
      new gold standard of melasma treatment in Asia. OBJECTIVE: To evaluate the
      efficacy and safety of low-fluence 1064-nm QSNY in Asian patients with melasma.
      METHODS: Data of patients with melasma treated with low-fluence QSNY in the
      department of dermatology at the Korea University Anam Hospital were reviewed
      retrospectively. A 1064-nm QSNY with 8 mm spot size and fluence of 1.2-2.0 J/cm2
      at 10 Hz was used. The results were evaluated using the modified Melasma Area and
      Severity Index (mMASI) score and the physician's global assessment (PGA).
      RESULTS: A total of 40 Korean patients with Fitzpatrick skin type III to IV were
      included. Patients were treated for a median of 10 sessions at a median of 1-week
      intervals. The mean mMASI score decreased by 54.23% from a baseline of 3.19 +/-
      2.64 to 1.46 +/- 1.06 after treatment. On PGA, 1 out of 40 patients (2.5%) showed
      excellent improvement, 14 (35%) good, 15 (37.5%) fair, 6 (15%) poor, and 4 (10%)
      no improvement. However, two patients showed mottled hypopigmentation and rebound
      hyperpigmentation. CONCLUSION: Low-fluence 1064-nm QSNY appears to be a safe and
      effective treatment for Asian patients with melasma.

PMID- 30280475
TI  - Comparison of coronary revascularization appropriateness for non-acute coronary
      syndrome cases under the 2017 update vs the 2012 appropriate use criteria.
AB  - OBJECTIVES: To compare coronary revascularization appropriateness for non-acute
      coronary syndrome cases under the 2017 update vs the 2012 appropriate use
      criteria (AUC). BACKGROUND: In 2017, the 2012 AUC for coronary revascularization
      were updated. We examined how applying these new 2017 updates to our previous
      inappropriate cases would change their appropriateness. METHODS: We identified 50
      cases of patients who underwent coronary revascularization for stable ischemic
      heart disease who were deemed inappropriate under the 2012 AUC. Two separate
      physicians reviewed the cases and applied a new AUC based on the 2017 AUC. Next,
      if there was a change, the reason was identified. RESULTS: Average age was 64,
      majority being male (29; 58%). Forty-two (84%) were asymptomatic upon
      presentation. Most cases (27, 54%) dealt with percutaneous coronary intervention
      (PCI) of the right coronary artery. After applying the 2017 AUC, 34 of the 50
      inappropriate failures (68%) would be changed from "inappropriate" to "may be
      appropriate care." Of the 34 cases, 25 (73.5%) were changed due to the new AUC no
      longer expecting the patient to be on >=2 anti-angina medications prior to PCI.
      Of the 34 cases, eight (23.5%) were changed due to the new AUC expanding the use
      of non-invasive modalities. CONCLUSIONS: Applying the 2017 AUC led to a
      statistically higher number of cases being deemed "may be appropriate." The most
      common cause for the change included the change in requirement for anti-angina
      regimen and the expanded role of non-invasive modalities.

PMID- 30280476
TI  - Rate of major adverse renal or cardiac events with iohexol compared to other low
      osmolar contrast media during interventional cardiovascular procedures.
AB  - OBJECTIVE: This study assessed the rate of major adverse renal or cardiac events
      (MARCE) when iohexol is used during interventional cardiovascular procedures
      compared to other low osmolar contrast media (LOCMs). BACKGROUND: Interventional
      cardiovascular procedures are often essential for diagnosis and treatment, the
      risk of MARCE should be considered. METHODS: Data were derived from the Premier
      Hospital Database January 1, 2010 through September 30, 2015. Patient encounters
      with an inpatient primary interventional cardiovascular procedure with a single
      LOCM (iohexol, ioversol, ioxilan, ioxaglate, or iopamidol) were included. The
      primary outcome was a composite endpoint of MARCE, which included: renal failure
      with dialysis, acute kidney injury (AKI) with or without dialysis, contrast
      induced AKI, acute myocardial infarction, angina, stent occlusion/thrombosis,
      stroke, transient ischemic attack, or death. Multivariable regression analysis
      was performed using the hospital fixed-effects specification to assess the
      relationship between MARCE and iohexol compared to other LOCMs, while controlling
      for patient demographics, comorbid conditions and reason for hospitalization. As
      a sensitivity analysis, direct comparisons of iohexol were made to other LOCMs.
      RESULTS: A total of 458,091 inpatient encounters met inclusion criteria of which
      26% used iohexol and 74% used other LOCMs. Results of multivariable modeling
      revealed no differences in MARCE rates between iohexol and other LOCMs. When
      direct comparisons of iohexol vs. ioversol and iopamidol were modeled, no
      differences in MARCE nor the renal component of MARCE were found. CONCLUSIONS: In
      this retrospective multicenter study, there were no differences in MARCE events
      with iohexol compared to other LOCMs during inpatient interventional
      cardiovascular procedures.

PMID- 30280477
TI  - Using the Value of Information to improve conservation decision making.
AB  - Conservation decisions are challenging, not only because they often involve
      difficult conflicts among outcomes that people value, but because our
      understanding of the natural world and our effects on it is fraught with
      uncertainty. Value of Information (VoI) methods provide an approach for
      understanding and managing uncertainty from the standpoint of the decision maker.
      These methods are commonly used in other fields (e.g. economics, public health)
      and are increasingly used in biodiversity conservation. This decision-analytical
      approach can identify the best management alternative to select where the
      effectiveness of interventions is uncertain, and can help to decide when to act
      and when to delay action until after further research. We review the use of VoI
      in the environmental domain, reflect on the need for greater uptake of VoI,
      particularly for strategic conservation planning, and suggest promising areas for
      new research. We also suggest common reporting standards as a means of increasing
      the leverage of this powerful tool. The environmental science, ecology and
      biodiversity categories of the Web of Knowledge were searched using the terms
      'Value of Information,' 'Expected Value of Perfect Information,' and the
      abbreviation 'EVPI.' Google Scholar was searched with the same terms, and
      additionally the terms decision and biology, biodiversity conservation, fish, or
      ecology. We identified 1225 papers from these searches. Included studies were
      limited to those that showed an application of VoI in biodiversity conservation
      rather than simply describing the method. All examples of use of VOI were
      summarised regarding the application of VoI, the management objectives, the
      uncertainties, the models used, how the objectives were measured, and the type of
      VoI. While the use of VoI appears to be on the increase in biodiversity
      conservation, the reporting of results is highly variable, which can make it
      difficult to understand the decision context and which uncertainties were
      considered. Moreover, it was unclear if, and how, the papers informed management
      and policy interventions, which is why we suggest a range of reporting standards
      that would aid the use of VoI. The use of VoI in conservation settings is at an
      early stage. There are opportunities for broader applications, not only for
      species-focussed management problems, but also for setting local or global
      research priorities for biodiversity conservation, making funding decisions, or
      designing or improving protected area networks and management. The long-term
      benefits of applying VoI methods to biodiversity conservation include a more
      structured and decision-focused allocation of resources to research.

PMID- 30280478
TI  - Angiographic characteristics and long-term prognostic impact of coronary artery
      disease in survivors after sudden cardiac arrest with a non-diagnostic
      electrocardiogram.
AB  - OBJECTIVES: Our purpose was to describe the prevalence, distribution, extension,
      and prognostic value of coronary artery disease (CAD) in patients resuscitated
      from sudden cardiac arrest (SCA) with non-diagnostic electrocardiogram (ECG).
      BACKGROUND: The impact of CAD and the indication for cardiac catheterization (CC)
      in patients resuscitated from SCA with non-diagnostic ECG are uncertain. METHODS:
      We included prospectively and consecutively 545 patients resuscitated from SCA
      with at least one CC during hospitalization. From them, 203 patients with a non
      diagnostic ECG formed our study population. Patients were followed-up 5 years
      after discharge. RESULTS: Overall, 125 (61.6%) patients had significant CAD, and
      at least one acute culprit lesion was found in 25 (12.4%). Regarding the burden
      and complexity of CAD, 78 (38.4%) patients had a CAD Prognostic Index of 0 and a
      SYNTAX score of 0. There was higher 5-year mortality only in patients with very
      high burden of CAD: three vessels with severe stenosis (P = 0.015) and CAD
      Prognostic Index Score >= 56 (P < 0.001). Tertiles of SYNTAX score did not
      predict higher 5-year mortality. CONCLUSIONS: In survivors from SCA with a non
      diagnostic ECG, significant CAD is highly prevalent. SYNTAX score was not
      associated with a different long-term prognosis in this patient population.
      Patients with severe disease in the three main coronary vessels and patients with
      higher (>=56) CAD Prognostic Index Score had a worse long-term prognosis.

PMID- 30280480
TI  - Long-term outcome of brachytherapy treatment for coronary in-stent restenosis:
      Ten-year follow-up.
AB  - OBJECTIVES: The objective of this study was to determine the long-term major
      adverse cardiac events (MACE) in patients treated with intracoronary
      brachytherapy (ICBT) for coronary in-stent restenosis (ISR). BACKGROUND: ICBT was
      commonly used to treat coronary ISR prior to the availability of drug-eluting
      stents (DES). The long-term outcomes of ICBT for ISR remain unknown. METHODS: Six
      hundred and eighty consecutive patients who underwent ICBT treated for ISR
      between September 1998 and April 2005 were included in the study. Clinical and
      angiographic data were collected and the long-term MACE were measured for all
      cause death, myocardial infarction (MI), and target vessel revascularization
      (TVR) at 10-year follow-up. RESULTS: Patients were 63 +/- 11 years old (66%
      male). The majority of patients were treated with a bare metal stent 670/680
      (99%) prior to ICBT. Significant baseline clinical findings include high
      incidence of smokers 479/680 (70%), hyperlipidemia 638/680 (94%), and multivessel
      disease 526/680 (77%). The majority of target lesions were diffuse 407/680 (60%),
      and either in the left anterior descending 258/680 (38%) or right coronary artery
      215/680 (32%). At 10-year follow-up, the rate of death was 25%, MI was 22.4%, and
      TVR was 48%. CONCLUSION: MACE at 10-year follow-up following ICBT for ISR
      indicates steady rate of death and MI and declining rate of TVR after 5 years.

PMID- 30280479
TI  - Favorable neurological outcome after ischemic cerebrovascular events in patients
      treated with percutaneous left atrial appendage occlusion compared with warfarin.
AB  - OBJECTIVES: This study sought to investigate neurological disability after
      ischemic cerebrovascular events in patients treated with left atrial appendage
      (LAA) occlusion compared with those on warfarin. BACKGROUND: Prior studies
      demonstrated that cerebrovascular events after LAA occlusion in patients with
      nonvalvular atrial fibrillation (NVAF) is largely nondisabling. METHODS: From the
      1,189 patients in the Korean LAA Occlusion and European Amplatzer Cardiac Plug
      Multi-Center Registry, 24 patients who experienced ischemic cerebrovascular
      events after LAA occlusion were enrolled. The neurological outcomes were compared
      with those in 68 patients who experienced an ischemic cerebrovascular event while
      on warfarin (Yonsei Stroke Registry). A modified Rankin scale (mRS) score of 3-6
      categorized the cerebrovascular event as disabling. The mRS at discharge and at 3
      and 12 months postcerebrovascular event in the two groups was compared. RESULTS:
      The percentages of disabling cerebrovascular events were 37.5% and 58.8% at
      discharge (P = 0.07), 20.8% and 42.6% at 3 months (P = 0.08), and 12.5% and 39.7%
      at 12 months (P = 0.02) in the LAA occlusion and warfarin groups, respectively.
      The mRS was significantly lower in the LAA occlusion group at discharge and at 3
      months (P < 0.01) and 12 months (P < 0.01) postcerebrovascular event despite no
      significant difference in mRS before cerebrovascular events (P = 0.98). Patients
      in the LAA occlusion group demonstrated a significant reduction in mRS between
      discharge and 12 months (P < 0.01), unlike patients in the warfarin group (P =
      0.10). CONCLUSIONS: Ischemic cerebrovascular events in patients who previously
      underwent percutaneous LAA occlusion for NVAF were more favorable than in
      patients on warfarin.

PMID- 30280481
TI  - Effect of percutaneous paravalvular leak closure on hemolysis.
AB  - OBJECTIVE: To study the effect of percutaneous paravalvular leak closure on
      hemolysis. BACKGROUND: Although transcatheter PVL closure reduces heart failure
      and mortality in symptomatic patients with paravalvular leaks (PVL), little is
      known about its effect on hemolysis. METHODS: We retrospectively analyzed
      patients undergoing transcatheter mitral or aortic PVL closure (January 2005
      December 2016) at Mayo Clinic. Patients with anemia or abnormal hemolysis markers
      (LDH, haptoglobin) were included in the analysis. The primary outcome was defined
      as hemoglobin increase >= 1.5 mg/dL, decrease in LDH above median or improvement
      in haptoglobin. Univariate and multivariate binary logistic regression modeling
      were used to determine predictors of successful treatment of hemolysis. RESULTS:
      Final study population included 168 patients (130 [77%] mitral, 38 [23%] aortic
      PVL). Primary outcome occurred in 70 patients (42%). Hemoglobin increased by 1.74
      +/- 1.69 mg/dL in patients who reached primary outcome. 57/168 (34%) patients
      required blood transfusion prior to PVL closure compared to 35/168 (21%)
      postprocedure. The mean reduction in LDH was 403 U/L. Multivariate regression
      showed that patients with mechanical valves were more likely to have successful
      outcome (P = 0.044). CONCLUSION: Percutaneous PVL closure is associated with
      modest improvement in hemolysis markers, increase in hemoglobin levels and
      reduction in blood transfusion requirements. This benefit is most significant in
      patients with mechanical valves.

PMID- 30280482
TI  - Prospective, large-scale multicenter trial for the use of drug-coated balloons in
      coronary lesions: The DCB-only All-Comers Registry.
AB  - OBJECTIVES: This prospective, observational all-comers registry assessed the
      safety and efficacy of a Drug Coated Balloon-only strategy (DCB-only) in patients
      with coronary lesions. BACKGROUND: Data regarding the performance of a DCB-only
      approach, especially in patients with previously untreated de-novo coronary
      artery disease (CAD), are still limited. METHODS: This study was conducted as an
      international, multicenter registry primarily enrolling patients with de-novo
      CAD. However, it was also possible to include patients with in-stent restenosis
      (ISR). The primary endpoint was the rate of clinically driven target lesion
      revascularization (TLR) after 9 months. RESULTS: A total of 1,025 patients with a
      mean age of 64.0 +/- 11.2 years were enrolled. The majority of treated lesions
      were de-novo (66.9%), followed by drug-eluting-stent ISR (DES-ISR; 22.6%) and
      bare-metal-stent ISR (BMS-ISR; 10.5%). The TLR rate was lower in the de-novo
      group (2.3%) when compared to BMS- (2.9%) and DES-ISR (5.8%) (P = 0.049).
      Regarding MACE, there was a trend toward fewer events in the de-novo group (5.6%)
      than in the BMS- (7.8%) and DES-ISR cohort (9.6%) (P = 0.131). Subgroup analyses
      revealed that lesion type (95% CI 1.127-6.587); P = 0.026) and additional stent
      implantation (95% CI 0.054-0.464; P = 0.001) were associated with higher TLR
      rates. CONCLUSIONS: Our results show that DCB-only angioplasty of de-novo
      coronary lesions is associated with low MACE and TLR rates. Thus, DCBs appear to
      be an attractive alternative for the interventional, stentless treatment of
      suitable de-novo coronary lesions.

PMID- 30280483
TI  - Effect of platelet-rich plasma on proliferation and migration in human dermal
      fibroblasts.
AB  - BACKGROUND: Platelet-rich plasma (PRP) is a blood fraction that contains high
      concentrations of several growth factors. PRP has been recently used in skin
      wound healing and rejuvenation. However, the precise molecular mechanisms
      underlying PRP-induced wound healing are unknown. AIMS: This study aimed to
      evaluate the effects of PRP on extracellular matrix remodeling, which requires
      the activation of dermal fibroblasts. METHODS: Cell proliferation and migration
      assay, enzyme-linked immunosorbent analysis, and Western blotting were performed
      on PRP-treated human skin fibroblasts. RESULTS: Platelet numbers were enhanced by
      4.6-fold in PRP compared to that in whole blood. PRP stimulated the proliferation
      and migration of human dermal fibroblasts and increased the expression of human
      procollagen I alpha 1, elastin, MMP-1, and MMP-2 in human dermal fibroblasts. PRP
      treated human dermal fibroblasts also showed a dramatic reduction in the
      phosphorylation of c-Jun N-terminal kinase (JNK), whereas total JNK levels were
      not significantly reduced. CONCLUSIONS: Collectively, PRP induced increased
      expression of type I collagen, elastin, MMP-1, and MMP-2, thereby accelerating
      wound healing. Our findings reveal basic mechanisms underlying PRP-mediated
      tissue remodeling. Thus, these results could be exploited for clinical
      dermatology and skin rejuvenation.

PMID- 30280484
TI  - Effectiveness of short-pulse width Nd:YAG in laser hair reduction.
AB  - INTRODUCTION: Laser hair reduction (LHR) is a safe and effective way of reducing
      unwanted hairs over body. Long-pulse Nd:YAG laser has over the years, been proven
      to be particularly safe and effective in darker skin types. While conventionally,
      long-pulse Nd:YAG laser has been used, recently short-pulse width Nd:YAG laser of
      0.6-1.6 ms which is 10-50 times less than the standard method (long-pulse) of
      Nd:YAG LHR, has become available. OBJECTIVES: To study the effectiveness of short
      pulse width Nd:YAG laser in LHR in Indian patients. MATERIAL AND METHODS: This
      was a prospective observational study conducted over a period of 1 year. Fifty
      female patients with fitzpatrick skin type 3-5 were included. Patients underwent
      four sessions of LHR, with an interval of 6 weeks and then follow up was done for
      6 months after the last session. RESULTS: The mean age of patient was 29.92 years
      ranging from 17 to 48 years. After finishing four sessions of LHR procedure 58%,
      34%, 6%, and 2% of the patients showed excellent, good, moderate, and poor
      improvement respectively. No complications were seen during the treatment and
      after follow-up. Statistical analysis by paired t test showed the results to be
      statistically significant. CONCLUSION: Hair reduction using unique short-pulse
      width Nd:YAG laser is easy to use, safe, and effective in Indian skin.

PMID- 30280485
TI  - The effect of NB-UVB on noncultured melanocyte and keratinocyte transplantation
      in treatment of generalized vitiligo using two different donor-to-recipient
      ratios.
AB  - BACKGROUND: The melanocyte and keratinocyte transplantation procedure (MKTP) is a
      safe and effective procedure in treatment of vitiligo. Major advantage of this
      technique is that a small area of donor skin is needed to cover a large recipient
      area. To date, there is no consensus on the optimal donor-to-recipient ratio
      (D/R) required to achieve acceptable repigmentation following melanocyte and
      keratinocyte transplantation procedure (MKTP) in generalized vitiligo. It has
      been postulated that the addition of post-transplantation phototherapy may
      enhance the results. This is first study to assess two different (D/R) ratios
      with or without adjuvant phototherapy. OBJECTIVE: To compare the repigmentation
      after MKTP using two different D/R ratios (1/3 and 1/10) with and without
      adjuvant phototherapy (NB-UVB). METHODS AND MATERIALS: In this non randomized
      prospective clinical trial, 42 patients with stable generalized vitiligo
      bilateral and symmetrical in distribution were included. Patients were divided
      into two groups, 21 patients with a total of 50 lesions were treated with MKTP
      using a D/R ratio of 1/3 (Group I; 3000 +/- 500 cell/mm2 ) and the other 21
      patients with a total of 52 lesions were treated by MKTP using a D/R ratio of
      1/10 (Group II; 1000 +/- 200 cell/mm2 ). To study the role of adjuvant
      phototherapy on repigmentation, lesions in each patient were divided into two
      subgroups (a and b): lesions in subgroups Ia and IIa (did not receive NB-UVB) and
      lesions in subgroups Ib and IIb (received adjuvant phototherapy NB-UVB, two
      sessions per week for 6 months). The overall grading of repigmentation used was
      excellent (90%-100% repigmentation), good (75%-89%), fair (50%-74%), and poor
      (<50%). Also, the percentage of VASI change and color matching were used to
      assess the results. The study design was approved by the ethical committee of the
      Faculty of Medicine, Assiut University (IRB attached). RESULTS: The mean
      percentage of repigmentation was significantly better in group I than group II
      cases in both areas with or without adjuvant NB-UVB. It was 86.00 +/- 16.21 and
      87.62 +/- 11.66 in subgroups Ia and Ib, respectively, vs 24.14 +/- 18.08 and
      29.98 +/- 16.34 in subgroups IIa and IIb, respectively (P value was 0.000). The
      percent of excellent response was significantly better in group I than group II.
      It was 60% and 64% in subgroups Ia and Ib, respectively, and 7.6 and 11.5 in
      subgroups IIa and IIb, respectively (P value was 0.000). The mean percentage of
      VASI change was significantly better in group I than group II cases in both
      areas. It was -90.74 +/- 15.84 and -92.06 +/- 11.86 in subgroups Ia and Ib,
      respectively, vs -23.10 +/- 32.85 and -26.03 +/- 35.15 in subgroups IIa and IIb,
      respectively (P value was 0.000). The percent of excellent color match was better
      in group I than group II. It was 84% and 88% in subgroups Ia and Ib,
      respectively, vs 34.6 in both subgroups IIa and IIb (P < 0.05). A higher density
      of epidermal cells was transplanted in the recipient area in group I (3000 +/-
      500 cell/mm2 ) compared to group II (1000 +/- 200 cell/mm2 ). There were no
      statistically significant differences between subgroups (Ia vs Ib and IIa vs IIb)
      although percentage of repigmentation was slightly better in NB-UVB subgroups.
      CONCLUSIONS: The higher density of epidermal cells used in the suspension, the
      higher the percentage of repigmentation obtained. The usage of adjuvant
      phototherapy following NKMT can enhance the repigmentation response.

PMID- 30280486
TI  - Closure of mid-bore venotomies with VASCADE VCD after right and left heart
      catheterization.
AB  - OBJECTIVE: This single-center, retrospective analysis investigated the clinical
      outcomes of a novel vascular closure device (VASCADE, Cardiva Medical, Santa
      Clara, CA) for closure of 7F femoral venotomies. BACKGROUND: The VASCADE closure
      device has been widely used to close arteriotomy sites following femoral
      procedures; however, little data have been published regarding the device's
      utility in closure of venotomy sites after procedures such as right-heart
      catheterization. METHODS: This was a retrospective analysis of outcomes in 102
      consecutive patients who underwent venous closure using the VASCADE device
      following diagnostic right and left-heart catheterization between March 2017 and
      May 2018. Patients' age, gender, valvular disease status, comorbidities, and
      periprocedural use of antiplatelet/anticoagulant therapy were analyzed. RESULTS:
      Closure was successful in 99% (101/102) of patients with respect to achieving the
      primary outcome of rapid hemostasis in <=3 min. There was one device failure
      requiring manual compression, with no further complications. There were no other
      related adverse events or complications through 30 days of follow-up.
      CONCLUSIONS: The VASCADE device achieved venous hemostasis in nearly all our
      patients. We believe devices for venous closure can aid in improving patient
      experience, safety, and efficiency during these procedures.

PMID- 30280487
TI  - Is a covered stent justifiable in the treatment of coronary artery perforation?
      An observational analysis of long-term results of two different covered stent
      types.
AB  - OBJECTIVES: In this retrospective observational study, we investigate outcome of
      patients treated with or without covered stent (CS) implantation in the
      management of coronary artery perforation (CAP) during coronary intervention.
      BACKGROUND: CSs have shown to be effective devices to achieve acute hemostasis in
      large CAP. However, doubts have been raised regarding their long-term outcome.
      METHODS: Data of 19 061 PCI procedures during a 10-year period were reviewed.
      Fifty-five cases of large CAP were withheld (Ellis type 2, 3 or cavity spilling).
      All medical and procedural records of these cases were retrospectively reviewed.
      RESULTS: Twenty-four (43.6%) patients were treated with CS implantation (15
      polytetrafluoroethylene and 9 pericardium CSs). Twenty-six (47.3%) patients were
      managed without CS implantation, of whom five had unsuccessful delivery of a CS
      (stent delivery failure 17.2%). Although significantly more Ellis type-3
      perforations were present in the CS group compared to the Non-CS group (75.0% vs
      45.2%; P = 0.03), in-hospital mortality was not significantly different (8.3% vs
      6.4%; [P = 0.79]). We observed a high rate of CS restenosis (29.2%) but a lower
      rate of CS thrombosis (4.2%). Despite these observations, 5-year MACE and all
      cause mortality were not significantly different between CS and Non-CS group
      (respectively, 58.8% vs 50.0% (P = 0.26) and 26.7% vs 13.3% (P = 0.36)).
      CONCLUSION: Although deliverability of CSs was not flawless and a high rate of CS
      restenosis appeared, short- and long-term outcome were comparable between
      patients treated with or without CS. Therefore, CSs are justifiable in the
      treatment of CAP.

PMID- 30280488
TI  - Truck-mounted area-wide applications of larvicides and adulticides for extended
      suppression of adult Aedes albopictus.
AB  - BACKGROUND: Given the lack of vaccines for most vector-borne diseases, vector
      control is often the primary option for disease control. Aedes albopictus are
      difficult to control because the immatures primarily develop in containers
      ubiquitous in residential properties. Conventional adulticide campaigns often
      result in brief, rebounding population declines, so incorporating new techniques
      into an integrated pest management program is imperative. We performed combined
      area-wide applications of the larvicides Bacillus thuringiensis var. israelensis
      and pyriproxyfen with the adulticide sumithrin and prallethrin to achieve
      extended suppression of Ae. albopictus populations in Trenton, NJ, USA. We
      deployed bioassay cups to assess the spatial penetration and efficacy of the
      applications. RESULTS: Inhibition of adult emergence was significantly higher in
      the treatment bioassay cups than in laboratory controls (z = 4.65, P < 0.0001)
      and field control bioassay cups (z = 8.93, P < 0.0001). We observed a lower trend
      in adult numbers following season-long combined application of pyriproxyfen and
      adulticide, with numbers of adult Ae. albopictus at the treatment site up to five
      times lower than at the control site. CONCLUSION: Pyriproxyfen is a powerful
      mosquito larvicide and pupacide with low mammalian toxicity that shows promise
      for area-wide vehicle-mounted (either ground or airborne) applications. (c) 2018
      Society of Chemical Industry.

PMID- 30280489
TI  - Reducing radiation exposure by lowering frame rate in children undergoing cardiac
      catheterization: A quality improvement study.
AB  - INTRODUCTION: Reduction of radiation dosage in the pediatric cardiac
      catheterization laboratory (PCL) is important to reduce the risk of its
      stochastic effect in children with congenital heart disease. Lowering the frame
      rate would reduce radiation dosage possibly at the expense of image quality,
      potentially resulting in higher fluoroscopic time and procedural complication
      rate. METHODS: The data were retrospectively analyzed in three eras: era 1 (n =
      234), cineangiography 30 frames/sec (f/s) and fluoroscopy 15 pulse/sec (p/s); era
      2 (n = 381), cineangiography 30 f/s and fluoroscopy 6 p/s; and era 3 (n = 328),
      cineangiography 15 f/s and fluoroscopy 6 p/s. Also, three operators blinded to
      the frame rate setting evaluated cineangiography image quality. In this study,
      the impact of lowering the default frame rates on radiation dosage, fluoroscopic
      time, contrast volume, diagnostic image quality, and complication rates in the
      PCL was assessed. RESULTS: Overall radiation dosage progressively declined during
      these eras (70.0 vs 64.1 vs 36.6 uGym2 /kg, P < .001) without a difference in
      significant adverse event rates. There was no significant increase in either
      fluoroscopy time or contrast volume. There was no difference in the diagnostic
      image quality between cineangiography 30 and 15 f/s. Lowering the default
      frame/pulse rates of both fluoroscopy and cineangiography significantly decreased
      the overall radiation dosage in the PCL. Importantly, fluoroscopy time, contrast
      volume, and complication rates did not increase while maintaining diagnostic
      image quality. CONCLUSION: This quality improvement project proved successful in
      lowering radiation dosage without compromising the efficacy and safety of
      catheterizations.

PMID- 30280490
TI  - Correlation between retinal vein occlusion and cancer - a nationwide Danish
      cohort study.
AB  - PURPOSE: To explore the association between retinal vein occlusion (RVO) and
      incident cancer. METHODS: All Danish citizens with a first-time diagnosis of RVO
      and no previous diagnosis of cancer in the period from 1 January 2004 to 31
      December 2014 were included. Five likewise cancer-free, age- and gender-matched
      controls were included in a control cohort. All were followed up for 5 years or
      until either first diagnosis of cancer or death. Proportional hazards models with
      adjustment for age, gender, year of diagnosis and covariates and death as
      competing risk were used to estimate the risk of being diagnosed with cancer.
      RESULTS: There were 7963 RVO patients without cancer at the time of diagnosis,
      and all could be matched to likewise cancer-free controls. Half of RVO patients
      were male, and the median age at RVO diagnosis was 70 years (61-79). The control
      cohort was similar in terms of gender and age. The risk of cancer within 1 year
      was 1.8 among RVO patients and 1.5 among controls. The crude risk of cancer was
      1.22 (1.11;1.34) and upon full adjustment 1.15 (1.05;1.27). No time dependency
      was detected, and the types of cancer developed in RVO patients and controls were
      similar. CONCLUSION: Retinal vein occlusion (RVO) diagnosis is associated with an
      increased risk of being diagnosed with cancer. This risk is likely to reflect
      shared risk factors rather than a causal association.

PMID- 30280492
TI  - Is population-based screening for rheumatic heart disease precluded by the Cairo
      accord? Echocardiography...and beyond.
AB  - In the 2017, "Cairo Accord on Rheumatic Heart Disease-From Molecules to The
      Global Community" experts from endemic areas enumerated an approach to reduce the
      population burden of rheumatic heart disease. The 10 key recommendations include
      immediate logistical objectives as well as domains for further study.
      Echocardiographic population screening programs were relegated to research alone.
      Given the large body of supporting data, relegating echo screening to an
      investigational modality is an opportunity lost.

PMID- 30280491
TI  - Clinical and biological relevance of genetic alterations in pediatric T-cell
      acute lymphoblastic leukemia in Taiwan.
AB  - BACKGROUND: The leukemogenesis of T-cell acute lymphoblastic leukemia (T-ALL)
      involves multistep processes of genetic alterations. We aimed to determine the
      genetic alterations including common fusion transcripts, overexpression of T-cell
      transcription factor oncogenes, and deletion or mutation of targeted genes in
      pediatric T-ALL in Taiwan as well as their impact on outcomes in those treated
      with the Taiwan Pediatric Oncology Group-ALL-2002 protocol. PROCEDURE: Between
      1995 and 2015, bone marrow samples obtained from 102 children aged <18 years
      consecutively diagnosed with T-ALL were examined. Thirty-two genetic alterations
      were examined by reverse transcription polymerase chain reaction (PCR) assays-PCR
      based assays-followed by direct sequencing, real time quantitative PCR with
      TaqMan assays, or multiplex ligase probe amplification. RESULTS: TAL1
      overexpression, CDKN2A/2B deletions, and NOTCH1 mutation were the most frequent
      aberrations while none had NF1, SUZ12 deletion, JAK1 or JAK2 mutations, or NUP214
      ABL1 fusion in our cohort. The most frequent cooperating occurrence of genetic
      alterations included CDKN2A/2B and MTAP, MTAP and CDKN2B, LEF1 and PTPN2, and
      HOX11L2 and PHF6 mutation/deletion. NOTCH1 mutations conferred a favorable
      overall survival, whereas SIL-TAL1 fusion, TAL overexpression, LEF1 deletion, and
      PHF6 deletion/mutation were associated with an inferior outcome. By multivariate
      analysis, PHF6 mutation/deletion was the only independent predictor for inferior
      overall survival. CONCLUSIONS: The present study showed that the frequencies of
      genetic alterations in Taiwanese children with T-ALL differed considerably from
      those reported in Western countries. PHF6 mutation/deletion was an independently
      adverse predictor.

PMID- 30280493
TI  - The association between complement factor H rs1061170 polymorphism and age
      related macular degeneration: a comprehensive meta-analysis stratified by stage
      of disease and ethnicity.
AB  - PURPOSE: The strength of association between complement factor H (CFH) rs1061170
      polymorphism and age-related macular degeneration (AMD) differs between AMD
      subtypes and ethnicities. The main aim was to provide a systematic review and an
      updated meta-analysis stratified by stage of disease and ethnicity. METHODS: A
      literature search in the PubMed-Medline, EMBASE and Web of Science databases was
      conducted to identify epidemiological studies, published before September 2017,
      that included at least twp comparison groups (a control group with no signs of
      AMD and a case group of AMD patients). Genotype distribution, phenotype of the
      cases, ethnicity, mean age and gender ratio were collected. Odds ratios (ORs) and
      95%CIs were estimated under the allelic, homozygous and heterozygous models.
      Sensitivity and subgroup analyses, by AMD subtype and ethnicity, were performed.
      RESULTS: The meta-analysis included data of 27 418 AMD patients and 32 843
      controls from 76 studies. In Caucasians, the rs1061170 showed a significant
      association with early AMD (OR: 1.44; 95%CI 1.27-1.63), dry AMD (OR: 2.90; 95%CI
      1.89-4.47) and wet AMD (OR: 2.46; 95%CI 2.15-2.83), under an allelic model. In
      Asians, the rs1061170 showed a significant association with advanced AMD (OR:
      2.09; 95%CI 1.67-2.60), especially wet AMD (OR: 2.24; 95%CI 1.81-2.77).
      CONCLUSIONS: Our work provides a more comprehensive meta-analysis of studies
      investigating the effect of the CFH rs1061170 polymorphism on AMD risk. These
      findings not only improve the assessment of disease risk associated with the
      polymorphism, but also constitute a scientific background to be translated into
      clinical practice for AMD prevention.

PMID- 30280494
TI  - The first idea of IOL implantation.

PMID- 30280495
TI  - Determinants of mobile technology use and smartphone application interest in
      cancer patients.
AB  - BACKGROUND: Supportive care is a critical component of the treatment of cancer
      patients that is underutilized; patient lack of information about these services
      is an important barrier. Mobile technologies may be useful tools for delivering
      information, but cancer patient use of and interest in using them to learn about
      supportive care services have not been described. This study evaluates factors
      associated with cancer patient use of mobile technologies and interest in
      smartphone applications for information delivery about supportive care. METHODS:
      We conducted a cross-sectional survey among cancer patients from one urban
      academic hospital and 11 community hospitals. Patients self-reported use of
      mobile technologies and interest in smartphone applications. Multivariate
      logistic analysis was used to identify determinants of mobile technology use and
      smartphone interest. RESULTS: Among 631 participants, 466 (74%) reported regular
      use of mobile devices and 242 (39%) expressed an interest in supportive care
      information via smartphone applications. Patients under 45 were more likely to
      use a mobile device (Adjusted Odds Ratio [AOR] 6.8, 2.8-16.9 95% CI, P < 0.001)
      and were interested in smartphone applications for delivery of information (AOR
      3.2, 1.8-5.9 95% CI, P < 0.001). Non-white patients had similar use of mobile
      technology compared to whites but reported greater interest in smartphone
      application-based information (AOR 3.4, 2.1-5.5 95% CI, P < 0.001). CONCLUSION:
      Many patients expressed interest in smartphone application-based information
      about supportive care services, especially those who are younger and non-white.
      Future studies should investigate the characteristics of patients and smartphones
      applications that will optimize information delivery through a mobile technology
      platform.

PMID- 30280497
TI  - A novel genomic approach to herbicide and herbicide mode of action discovery.
AB  - A herbicide with a new mode of action has not been commercialized for more than
      30 years. A recent paper describes a novel genomic approach to herbicide and
      herbicide mode of action discovery. Analysis of a microbial gene cluster revealed
      that it encodes genes for both the biosynthetic pathway for production of the
      sesquiterpene aspterric acid and an aspterric acid-resistant form of dihydroxy
      acid dehydratase (DHAD), its target enzyme. Aspterric acid is weak compared with
      commercial synthetic herbicides, and whether DHAD is a good herbicide target is
      unclear from this study. Nevertheless, this genomic approach provides a novel
      strategy for the discovery of herbicides with new modes action. (c) 2018 Society
      of Chemical Industry.

PMID- 30280498
TI  - Soft contact lens induced blepharoptosis.

PMID- 30280496
TI  - Visual acuity and amblyopia prevalence in 11- to 12-year-old Danish children from
      the Copenhagen Child Cohort 2000.
AB  - PURPOSE: To evaluate the prevalence of amblyopia and associated biometric factors
      in Danish children. METHODS: Determination of best-corrected visual acuity (BCVA)
      using ETDRS charts, non-cycloplegic subjective refractioning guided by automated
      refractometry, axial length and corneal curvature, fundus photography and optical
      coherence tomography (OCT) in 1335 children from the population-based Copenhagen
      Child Cohort 2000 (CCC2000) Eye Study. Birth data were obtained from the Danish
      Medical Birth Registry. RESULTS: The mean (+/-SD) age of children was 11.7 (+/
      0.4) years, and 47% were boys. Amblyopia prevalence was 1.5 (95% CL 0.8-2.2) %.
      Unilateral amblyopic eyes [BCVA < 80 ETDRS letters (0.8 snellen) and >=2 lines
      difference between the eyes] was 0.6 (95% CL 0.3-1.0) mm shorter, 1.34 (95% CL
      0.30-2.37) D more hyperopic and had 0.79 (95% CL 0.14-1.44) D more astigmatism
      compared with fellow eyes. Compared with the right eyes of the non-amblyopic
      children, unilateral amblyopic eyes were 1.0 (95% CL 0.5-1.6) mm shorter, 2.48
      (95% CL 1.11-3.86) D more hyperopic, 1.09 (95% CL 0.43-1.75) D more astigmatic
      and had a 47 (95% CL 13-81) MUm thicker subfoveal choroid. CONCLUSION: Amblyopia
      was found in 1.5% of Danish children born 22 years after the inception of the
      nationwide preschool visual screening programme. Amblyopia was associated with
      anisometropia, astigmatism, a thicker subfoveal choroid and a history of
      childhood strabismus.

PMID- 30280499
TI  - Application of an activity-based receptor bioassay to investigate the in vitro
      activity of selected indole- and indazole-3-carboxamide-based synthetic
      cannabinoids at CB1 and CB2 receptors.
AB  - Synthetic cannabinoids (SCs) are the most chemically diverse group of new
      psychoactive substances. This group has been associated with several
      intoxications, many with fatal outcomes. Although advancements have been achieved
      in pharmacology, metabolism, and detection of these compounds in recent years,
      these aspects are still unresolved for many SCs. The aim of this study was to
      investigate the in vitro potency of 14 indole- and indazole-based SCs by applying
      a stable CB1 or CB2 receptor activation assay and correlating the activity with
      their structure. The half-maximal effective concentration (EC50 ) of 5
      chloropentyl, 5-bromopentyl, and 5-iodopentyl JWH-122 analogs varied from 74.1 to
      283.7 nM for CB1 and 7.05 to 23.4 nM for CB2, where the addition of a chlorine
      atom enhanced the potency at CB1 compared with the bromo and iodo analogs. AM
      2201 was the most active at CB1 within this naphthoylindole family, with an EC50
      of 23.5 nM but with the lowest efficacy (Emax 98.8%). Within the indole-3
      carboxamide derivatives, 5F-MDMB-PICA was the most active compound, with a
      CB1/CB2 EC50 of 3.26/0.87 nM and an Emax around three times higher than JWH-018.
      ADB-FUBINACA was the most potent tested SC overall, with a CB1/CB2 EC50 of
      0.69/0.59 nM, and an Emax around 3-fold higher than that for JWH-018 at CB1. The
      data obtained in this study confirm how small differences in the structure of SCs
      might lead to large differences in their activity, especially at CB1, which may
      be correlated with differences in their toxic effects in humans.

PMID- 30280500
TI  - Optimization of a dispersive liquid-liquid microextraction method followed by
      UHPLC analysis for fluoxetine quantification in environmental water resources.
AB  - Fluoxetine is the most prescribed drug for treatment of depression. Recently, its
      presence in aquatic environment has been receiving a growing interest as several
      studies assessed its effects on aquatic fauna. Therefore, it's important to have
      an analytical method capable of monitoring these compounds at low concentrations.
      In this study, a new method was developed based on dispersive liquid-liquid
      microextraction to preconcentrate fluoxetine in a small volume of water sample (6
      mL) before chromatographic analysis using ultra high performance liquid
      chromatography with fluorescence detection. Effect of composition and volume of
      extracting mixture, sample pH, vortexing time and salt addition were evaluated.
      Optimization of extraction conditions lead to an enrichment factor of 61 +/- 18.
      After extraction optimization, recovery percentages of fluoxetine spiked into
      different water matrices between 83-110% were obtained. For the optimized method,
      the calibration curve was obtained in the range of 160-2500 ng/L with a limit of
      detection of 98.9 ng/L and a limit of quantification of 329.8 ng/L.

PMID- 30280501
TI  - Miniphocibacter massiliensis gen. nov., sp. nov., a new species isolated from the
      human gut and its taxono-genomics description.
AB  - With the aim of describing the human microbiota by the means of culture methods,
      culturomics was developed in order to target previously un-isolated bacterial
      species and describe it via the taxono-genomics approach. While performing a
      descriptive study of the human gut microbiota of the pygmy people, strain
      Marseille-P4678T has been isolated from a stool sample of a healthy 39-year-old
      pygmy male. Cells of this strain were Gram-positive cocci, spore-forming, non
      motile, catalase-positive and oxidase-negative, and grow optimally at 37 degrees
      C under anaerobic conditions. Its 16S rRNA gene sequence exhibited 89.69% of
      sequence similarity with Parvimonas micra strain 3119BT (NR 036934.1), its
      phylogenetically closest species with standing in nomenclature. The genome of
      strain Marseille-P4678T is 2,083,161 long with 28.26 mol% of G+C content. Based
      on its phenotypic, biochemical, genotypic and proteomic profile, this bacterium
      was classified as a new bacterial genus and species Miniphocibacter massiliensis
      gen. nov., sp. nov. with the type strain Marseille-P4678T .

PMID- 30280502
TI  - Pulsatile Glenn as long-term palliation for single ventricle physiology patients.
AB  - OBJECTIVE: There are limited studies analyzing pulsatile Glenn as a long-term
      palliation strategy for single ventricle patients. This study sought to determine
      their outcomes at a single institution. DESIGN: A retrospective review was
      performed. SETTING: Study performed at a single pediatric hospital. PATIENTS: All
      single ventricle patients who underwent pulsatile Glenn from 1995 to 2016 were
      included. OUTCOME MEASURES: Pulsatile Glenn failure was defined as takedown,
      transplant, or death. Further palliation was defined as Fontan, 1.5, or
      biventricular repair. Risk factors were assessed by Cox multivariable competing
      risk analyses. RESULTS: Seventy-eight patients underwent pulsatile Glenn at age 9
      months (interquartile range, 5-14). In total, 28% had heterotaxy, 18% had a
      genetic syndrome, and 24% had an abnormal inferior vena cava. There were 3 (4%)
      perioperative mortalities. Further palliation was performed in 41 (53%) patients
      with a median time-to-palliation of 4 years (interquartile range, 3-5). Pulsatile
      Glenn failure occurred in 10 (13%) patients with 8 total mortalities. Five- and
      10-year transplant-free survival were 91% and 84%, respectively. At a median
      follow-up of 6 years (interquartile range, 2-8), 27 patients (35%) remained with
      PG (age 7 years [interquartile range, 3-11], oxygen saturation 83% +/- 4%).
      Preoperative moderate-severe atrioventricular valve regurgitation (AVVR) (hazard
      ratio 7.77; 95% confidence interval 1.80-33.43; P =.005) and higher pulmonary
      vascular resistance (hazard ratio 2.59; 95% confidence interval 1.08-6.15; P
      =.031) were predictors of pulsatile Glenn failure after adjusting for covariates.
      Reaching further palliation was less likely in patients with preoperative
      moderate-severe AVVR (hazard ratio 0.22, 95% confidence interval 0.08-0.59; P
      =.002). CONCLUSION: Pulsatile Glenn can be an effective tool to be used in
      challenging circumstances, these patients can have a favorable long-term
      prognosis without reducing their suitability for further palliation.

PMID- 30280503
TI  - An Unprecedented, Lewis Acid-Mediated, Metal-Free Iodoannulation Strategy to
      Aromatic Iodides.
AB  - A direct transformation of ortho-alkynylated aromatic vinyl ethers to 1
      iodonaphthalenes and other iodo-heterocycles under mild Lewis acidic conditions
      in the presence of iodide as an external nucleophile is reported. The first
      example of an iodoannulation strategy using a nucleophilic source of iodine,
      coupled with good to excellent yields, exclusive alpha regioselectivity and a
      broad substrate scope makes this work an attractive avenue towards the
      construction of aromatic iodides.

PMID- 30280504
TI  - Laser pointer maculopathy - on the rise?
AB  - PURPOSE: To report symptoms and ocular pathology in 13 patients exposed to light
      from laser pointers. METHODS: We conducted a multi-centre consecutive case series
      from eight ophthalmology departments. RESULTS: Eleven boys aged 9-15 years and
      two girls aged 7 (sister of one of the aforementioned boys) and 12 years,
      respectively, were included. Laser wavelengths were 572 nm (green), 450 nm
      (blue), and red laser of unknown wavelength. Output powers were between 5 and
      5000 mW. Evaluation included slit lamp examination, colour fundus photography
      (CFP), and optical coherence tomography (OCT). All subjects complained of
      unilateral vision loss. Initial visual acuities in exposed eyes ranged from 0.05
      to 1.0 Snellen equivalent or better. Nine subjects showed pathology on CFP and
      OCT abnormalities. One subject had a macular hole, which closed after vitrectomy.
      Long-term visual acuity ranged from 0.3 to 1.0 Snellen equivalent or better.
      CONCLUSION: High-powered laser pointers have become readily available on the
      internet, and they have the potential to induce lasting visual loss. More than
      half of the published laser pointer maculopathy cases since the first incidence
      in 1999 have been published in 2014-2017. We suspect that incidence of exposure
      and subsequent visual loss is rising, and we encourage national legislators to
      regulate this market.

PMID- 30280505
TI  - Temporal and spatial expression of the Fox gene family in the Leech Helobdella
      austinensis.
AB  - The Forkhead box (Fox) gene family is an evolutionarily ancient gene family named
      after the Drosophila melanogaster forkhead gene (fkh). Fox genes are highly
      conserved transcription factors critical for embryogenesis and carcinogenesis. In
      the current study, we report a whole-genome survey of Fox genes and their
      expression patterns in the leech Helobdella austienesis. Phylogenetic analysis
      suggests that some Fox genes of leeches are correlated with other Lophotrochozoa
      and vertebrate Fox genes. Here we have performed semiquantitative reverse
      transcription polymerase chain reaction and whole-mount in situ hybridization of
      Fox genes throughout the embryonic development of H. austinensis. We found that
      each one of the leech Fox genes (FoxA1, FoxA3, FoxC, FoxL2, FoxO1, and FoxO2) is
      expressed in a specific set of cells or tissue type. From Stages 9-11, Hau-FoxA1
      was expressed in the foregut of the anterior region, and Hau-FoxL2 was expressed
      in mesodermal muscle fiber. Hau-FoxA3 was temporally expressed in the ventral
      neuroectoderm. At Stage 11, Hau-FoxC was expressed in the foregut. Hau-FoxO genes
      have a ubiquitous expression. Our results provide more insight on the
      evolutionary linkage and role of the Fox gene function in Bilateria.

PMID- 30280506
TI  - Associations between muscle mass, physical activity and dietary behaviour in
      adolescents.
AB  - BACKGROUND AND OBJECTIVES: Investigations in older individuals suggest that
      adequate nutrition and physical activity are particularly important to skeletal
      muscle health; however, data in adolescents are scant and equivocal. The
      objective was to determine the associations among diet, physical activity and
      skeletal muscle mass in adolescents. METHODS: We assessed diet with four to seven
      24-h recalls and physical activity by accelerometry in 640 adolescents. Using
      total body measures of fat-free soft tissue mass and fat mass assessed by dual
      energy X-ray absorptiometry, the skeletal muscle mass index (SMMI) was derived by
      adjusting fat-free soft tissue mass for fat mass in addition to height. RESULTS:
      Skeletal muscle mass index (SMMI) was negatively associated with consumption of
      sugar-sweetened beverages (standardized beta coefficient [beta] = -0.10, P =
      0.001) and saturated fats (beta = -0.28, P < 0.001). SMMI was positively
      associated with physical activity (moderate + vigorous) (beta = 0.20, P < 0.001).
      In further analysis, we observed a significant interaction between physical
      activity and sugar-sweetened beverage intake on SMMI (P = 0.002). CONCLUSION: Our
      study in adolescence suggests that physical activity and consumption of both
      sugar-sweetened beverages and saturated fats are associated with skeletal muscle
      mass. More importantly, our findings suggest that sugar-sweetened beverage intake
      may attenuate the beneficial effects of physical activity on skeletal muscle
      mass.

PMID- 30280507
TI  - Alterations in cerebral blood flow in children with congestive heart failure due
      to ventricular septal defect.
AB  - OBJECTIVE: We aimed to investigate the effect of ventricular septal defect (VSD)
      and heart failure on cerebral blood flow (CBF) in children, whether heart failure
      treatment improves CBF, and if there is any relationship between CBF and serum N
      terminal pro-brain natriuretic peptide (NT-proBNP) level. METHOD: Forty children
      with VSD (13 with heart failure) aged between 1 and 36 months were studied. The
      control group comprised 25 healthy children in the same age group. Maximum,
      minimum, and mean blood flow velocities and pulsatility indices of the right and
      left middle cerebral arteries were assessed using transcranial Doppler
      ultrasonography. Measurements of CBF and serum NT-proBNP levels were repeated in
      patients with heart failure a month post-heart failure treatment initiation. The
      groups were also compared in terms of defect diameters, cardiac structural
      changes, left ventricular systolic function, and findings related to pulmonary
      hypertension determined by echocardiography. Correlations between
      echocardiographic measurements and CBF parameters were analyzed. RESULTS:
      Although no significant difference was found between patient and control groups
      for CBF, right and left maximum CBF velocities significantly increased
      posttreatment in patients with heart failure (P = .04 and P = .01, respectively).
      Serum NT-proBNP levels in children with VSD associated with heart failure were
      significantly higher than those in children with VSD alone (P = .04) or in
      healthy children (P < .001). NT-proBNP levels were negatively correlated with
      right and left maximum CBF velocities (r = -0.39, P = .013 and r = -0.32, P =
      .043, respectively). CONCLUSION: Although no significant difference was found in
      CBF velocity among the study groups, increase in the CBF velocity post heart
      failure treatment and negative correlations between CBF velocity and both the VSD
      diameter and NT-proBNP levels indicate that the hemodynamic status due to VSD
      associated with heart failure has an effect on CBF.

PMID- 30280508
TI  - Electrochemical transition-metal-catalyzed C-H bonds functionalization:
      electricity as clean surrogates of chemical oxidants.
AB  - Transition-metal-catalyzed C-H activation attracts tremendous attentions in
      organic synthetic community because it obviates pre-functionalization of
      substrates.[1] Significant advances have been dedicated in the past several
      decades. However, it should be notated that super stoichiometric chemical
      oxidants, such as copper- or silver-based metal oxidants, benzoquinones (BQ),
      organic peroxides, potassium persulfate (K2S2O8), hypervalent iodine molecular
      oxygen (O2) and so on that are required for most of the reactions.[2] The
      disadvantages associated with above mentioned chemical oxidants, e.g. organic
      and/or heavy metal pollution, toxicity, highly risk of explosibility, especially
      because of the large scale usage and high costs limit its application in
      industry.[3] Thus, development of environmentally benign and user-friendly C-H
      bonds activation protocols in the absence of chemical oxidants would be urgently
      desirable. Organic electrosynthesis witnesses the renaissance because of its
      inherent advantages and unique characters.[4] Many advancements of
      electrochemistry in organic synthesis[5] as well as in organometallics have been
      made.[6] Redox reactions involve electron transfer. Therefore, in principle,
      losing or obtaining electrons on the surface of electrodes can be treated as
      clean surrogates of chemical redox reagents and thus environmental pollution,
      high costs, notorious toxicity and high risk of explosibility could be
      significantly reduced and/or suppressed. The result is fundamentally in line with
      the purpose of green chemistry. However, successful examples utilizing
      electricity as the clean surrogates of oxidants in transition-metal-catalyzed C-H
      activation are very elusive.[6] In order to aid the reader to understand this
      area, we wish to summarize recent progress in this area until the end of
      September 2018 in the format of minireview which is built on different transition
      metals.

PMID- 30280510
TI  - Retinal oxygen saturation as a non-invasive estimate for mixed venous oxygen
      saturation and cardiac output.
AB  - PURPOSE: To investigate the correlation between retinal vessel oxygen saturation
      and mixed venous oxygen saturation (SvO2-mixed ) and cardiac output (CO).
      METHODS: Retinal arterial (SaO2-retinal ) and venous (SvO2-retinal ) oxygen
      saturation were measured non-invasively with dual-wavelength retinal oximetry in
      subjects receiving invasive measurements of SvO2-mixed and CO through right heart
      catheterization. Correlations were analysed using Spearman's rank correlation
      coefficients and linear regression models. RESULTS: Fourteen patients (median age
      62.7 years, range: 21-77) were included in the analysis. When adjusted for age,
      SvO2-retinal showed a positive correlation with SvO2-mixed (beta = 0.80, p =
      0.003). Retinal arteriovenous oxygen saturation difference was significantly
      correlated with the inverse of CO (Spearman's rho = 0.59, p = 0.026). CONCLUSION:
      This pilot study provides proof of concept for the use of retinal oximetry as a
      non-invasive tool to assess systemic cardiovascular function.

PMID- 30280511
TI  - Changes in cardiometabolic markers in children with Prader-Willi syndrome and
      nonsyndromic obesity following participation in a home-based physical activity
      intervention.
AB  - BACKGROUND: Physical activity is associated with improved cardiometabolic markers
      in children with nonsyndromic obesity (NSO). Prader-Willi Syndrome (PWS) is a
      neurodevelopmental disorder characterized by obesity. OBJECTIVE: To compare
      cardiometabolic changes in response to a home-based parent-facilitated physical
      activity intervention between children with PWS or with NSO. METHODS:
      Participants included 18 children with PWS (age = 10.5 +/- 0.7y; body fat = 44.6
      +/- 2.0%) and 30 children with NSO (age = 9.7 +/- 0.2y; body fat = 44.8 +/-
      1.2%). Active Play @ Home was a 24-week physical activity intervention curriculum
      containing playground-based and active video games completed 4 days per week. Pre
      and post-intervention measurements included physical activity, body composition,
      blood samples analysed for glucose, insulin, lipids and cytokines, and insulin
      resistance computed using the homeostatic model of assessment for insulin
      resistance (HOMA-IR). RESULTS: All children (n = 48) showed a significant
      decrease in Interleukin-8 (3.64 +/- 0.24 vs. 3.06 +/- 0.22 pg/mL). Children with
      obesity who did not gain or who lost body fat percentage (n = 18) demonstrated a
      significant decrease in HOMA-IR (3.17 +/- 0.39 vs. 2.72 +/- 0.34) and an increase
      in high-density lipoprotein (44.30 +/- 2.51 vs. 47.29 +/- 2.59 mg/dL). All other
      measurements showed no significant changes. CONCLUSIONS: The most favourable
      changes in cardiometabolic factors were observed in children with nonsyndromic
      obesity who demonstrated no gain or a decrease in body fat percentage.

PMID- 30280509
TI  - Timing for cranioplasty to improve neurological outcome: A systematic review.
AB  - INTRODUCTION: Cranioplasty is a surgical technique applied for the reconstruction
      of the skullcap removed during decompressive craniectomy (DC). Cranioplasty
      improves rehabilitation from a motor and cognitive perspective. However, it may
      increase the possibility of postoperative complications, such as seizures and
      infections. Timing of cranioplasty is therefore crucial even though literature is
      controversial. In this study, we compared motor and cognitive effects of early
      cranioplasty after DC and assess the optimal timing to perform it. METHODS: A
      literature research was conducted in PubMed, Web of Science, and Cochrane Library
      databases. We selected studies including at least one of the following test: Mini
      Mental State Examination, Rey Auditory Verbal Learning Test immediate and 30-min
      delayed recall, Digit Span Test, Glasgow Coma Scale, Glasgow Outcome Scale, Coma
      Recovery Scale-Revised, Level of Cognitive Functioning Scale, Functional
      Independence Measure, and Barthel Index. RESULTS: Six articles and two systematic
      reviews were included in the present study. Analysis of changes in pre- and
      postcranioplasty scores showed that an early procedure (within 90 days from
      decompressive craniectomy) is more effective in improving motor functions
      (standardized mean difference [SMD] = 0.51 [0.05; 0.97], p-value = 0.03), whereas
      an early procedure did not significantly improve neither MMSE score (SMD = 0.06 [
      0.49; 0.61], p-value = 0.83) nor memory functions (SMD = -0.63 [-0.97; -0.28], p
      value < 0.001). No statistical significance emerged when we compared studies
      according to the timing from DC. CONCLUSIONS: It is believed that cranioplasty
      performed from 3 to 6 months after DC may significantly improve both motor and
      cognitive recovery.

PMID- 30280512
TI  - Endoplasmic reticulum stress-induced accumulation of VAMP721/722 requires
      CALRETICULIN 1 and CALRETICULIN 2 in Arabidopsis.
AB  - Excessive demand for translation and protein folding in the endoplasmic reticulum
      (ER) can cause ER stress in plants. Here, we show that CALRETICULIN 1 (CRT1) and
      CRT2 are critical components in the accumulation of VESICLE-ASSOCIATED MEMBRANE
      PROTEIN 721 (VAMP721) and VAMP722 during ER stress responses. We show that CRT2
      interacts with VAMP722 and that CRT1/2 post-translationally maintain elevated
      VAMP721/722 levels under ER stress. The greater growth inhibition in VAMP721/722
      deficient plants, induced by tunicamycin, suggests that plants under ER stress
      maintain physiological homeostasis, at least in part, by regulating VAMP721/722
      levels, as VAMP721/722 are known to participate in various biological processes.

PMID- 30280513
TI  - Impact of a 6-month family-based weight management programme on child food and
      activity behaviours: short-term and long-term outcomes of the PEACHTM
      intervention.
AB  - BACKGROUND: The PEACHTM randomized controlled trial measured changes to
      children's food and activity behaviours following participation in a weight
      management programme. We have previously reported a 10% reduction in body mass
      index z-score at intervention end (6-month post-baseline) that was maintained to
      24 months with no further intervention for the full study sample. OBJECTIVES: The
      objective of the study is to report changes in food and activity outcomes in the
      full sample at (i) the end of the 6-month intervention and (ii) 24-month post
      baseline (18-month post-intervention). METHODS: Changes in dietary and activity
      outcomes were assessed over time (baseline: n = 169, 8.1 +/- 1.2 years, body mass
      index z-score 2.72 +/- 0.62). Dietary intake was assessed using the Child Dietary
      Questionnaire, and times spent active and sedentary were assessed using a study
      specific questionnaire. Linear mixed models were used. RESULTS: There were
      significant time effects for all Child Dietary Questionnaire scores and activity
      and sedentary behaviours in the expected direction. Significant sex effects were
      observed for fruit and vegetable and sweetened beverages scores and for time
      spent in small screen-based activity. CONCLUSIONS: This is one of few child
      weight management studies to report short-term and long-term behaviour outcomes.
      It demonstrates that an intervention promoting food and activity behaviours
      consistent with guidelines can achieve modest changes, mediating improvements in
      relative weight.

PMID- 30280514
TI  - Downregulated miR-144-3p contributes to progression of lung adenocarcinoma
      through elevating the expression of EZH2.
AB  - OBJECTIVES: The intention of our study was to investigate the relationship
      between miR-144-3p and EZH2 as well as the effects of their interaction on cell
      propagation and invasiveness in lung adenocarcinoma (LUAD). METHODS: The
      expression levels of miR-144-3p and EZH2 in LUAD tissues and normal tissues were
      determined by qRT-PCR. The dual-luciferase reporter assay was utilized to
      validate the targeting relationship between miR-144-3p and EZH2. MTT assay and
      colony formation assay were performed to evaluate the viability and propagation
      of LUAD cells, while the effects of miR-144-3p and EZH2 on LUAD cell invasiveness
      were confirmed by transwell assay. Protein expression levels of VEGFA, MMP2, and
      MMP9 were measured by Western blot. Furthermore, xenograft tumor models were
      established to verify the effects of miR-144-3p on tumor formation and EZH2,
      VEGFA, MMP2 and MMP9 expressions in vivo. RESULTS: miR-144-3P was downregulated
      in LUAD tissues, and overexpression of miR-144-3p inhibited propagation and
      invasiveness of LUAD cells. EZH2 was a target of miR-144-3p and was highly
      expressed in LUAD cells. Knockdown of EZH2 could suppress the propagation and
      invasion of LUAD cells. Increased miR-144-3p expression exerted an inhibitory
      effect on LUAD tumor formation in vivo. CONCLUSION: Overexpression of miR-144-3p
      impeded the propagation and invasiveness of LUAD cells by targeting EZH2.

PMID- 30280515
TI  - Evaluation of tear meniscus by optical coherence tomography after different
      sodium hyaluronate eyedrops instillation.
AB  - PURPOSE: To evaluate changes in tear meniscus dynamics using optical coherence
      tomography (OCT) after the instillation of different concentrations of sodium
      hyaluronate (SH) ophthalmic solutions. METHODS: An experimental, double-masked,
      randomized study was performed. Twenty-three healthy subjects (16 women and seven
      men; mean age 23.57 +/- 2.56 years) participated in this study. About 35 MUl of
      0.1%, 0.2%, 0.3% SH ophthalmic solutions and saline solution was instilled in a
      randomly assigned eye. Tear meniscus measurements (height, depth and turbidity)
      were taken with OCT at 30 seconds and 1, 3, 5, 10 and 20 min after instillation.
      Subsequently, the Schirmer test and tear break-up time (TBUT) were evaluated.
      RESULTS: Tear meniscus depth and tear meniscus height showed a significant
      increase with all solutions compared to basal values: up to 3 min for 0.1% SH, up
      to 5 min for 0.2% and up to 10 min for 0.3% SH ophthalmic solution. Tear meniscus
      turbidity was also increased at 30 seconds for 0.1%, 0.2% and 0.3% SH artificial
      tears (p < 0.05). This increase remained significant for up to 1 min for 0.2% and
      0.3% SH solutions (p < 0.05). After 5 min of saline and 0.1% SH instillation, the
      turbidity was lower than basal values (p < 0.05). There was a significant
      increase in the TBUT for all solutions after instillation (p < 0.05). No
      differences between the Schirmer pre- and postinstillation were found (p > 0.05).
      Finally, the comfort was significantly improved for all ophthalmic solutions (p <
      0.05). CONCLUSION: Sodium hyaluronate (SH) ophthalmic solutions increase
      residence time in healthy subjects and are positively correlated with its
      concentration and therefore the viscosity.

PMID- 30280516
TI  - The vitreopapillary interface in healthy and glaucoma: posterior vitreous
      detachment in the vitreopapillary interface study.
AB  - PURPOSE: To investigate the vitreopapillary interface (VPI) in health and
      glaucoma according to the different stages of posterior vitreous detachment (PVD)
      formation. METHODS: Prospective single centre study including healthy subjects
      and glaucoma patients. PVD staging was performed with spectral domain optical
      coherence tomography. Gender, age, lens status and refractive error were assessed
      in both groups. Glaucoma patients additionally had a comprehensive
      ophthalmological investigation including intraocular pressure measurement, visual
      field testing and confocal imaging of the optic nerve head. RESULTS: Data on 523
      subjects (993 eyes) were included from the VPI study (clinicaltrials.gov
      NCT02290795) database (493 eyes of 258 healthy subjects and 500 eyes of 265
      glaucoma patients). Healthy subjects were significantly younger than primary open
      angle glaucoma patients (59.7 +/- 14.81 versus 70.0 +/- 10.78 years, p < 0.001),
      but were otherwise matched for refractive error and gender. Significantly more
      glaucomatous eyes were pseudophakic (26.6% versus 5.1%). Including only phakic
      nonoperated eyes from subjects between 50 and 80 years old decreased the age
      difference between healthy and open angle glaucoma (64.1 +/- 8.0 versus 65.9 +/-
      6.7 years, p = 0.051). Comparing these subgroups rendered similar average ages
      for PVD stages 0 and 4, in contrast to the significant older age for the glaucoma
      subgroup in stage 1 (64.1 +/- 6.01 versus 61.4 +/- 8.38 years, p < 0.001) and a
      trend towards significance in stage 3 (70.8 +/- 69.8 versus 67.5 +/- 5.92 years,
      p = 0.051). CONCLUSION: The VPI study is a large clinical trial investigating the
      VPI in health and glaucoma. A subset of glaucoma patients seems to experience
      stages 1-3 of PVD formation at older age compared to healthy subjects.

PMID- 30280517
TI  - Proteomic analysis of posterior capsular plaques in congenital unilateral
      cataract.
AB  - PURPOSE: To obtain insights on the protein composition of posterior capsular
      plaques (PCP) in congenital unilateral cataract with anterior vitreolenticular
      interface dysgenesis (AVLID). METHODS: Posterior capsular plaque's were collected
      during surgery in children presenting with congenital unilateral cataract.
      Surgeries were analysed focusing on the type of cataract, the integrity of the
      posterior capsule after peeling the PCP and the presence of vitreolenticular
      adherences when performing primary posterior capsulorhexis. Proteome analysis was
      performed on the collected PCPs. RESULTS: Posterior capsular plaques collection
      and proteome analysis were feasible from four children presenting with unilateral
      idiopathic congenital cataract and AVLID. A large portion of the proteins found
      in the PCPs was similar to the proteins known to be present in lens epithelial
      cells and fibres. Proteins like vimentin, fibronectin, collagen type I, collagen
      type VI and lumican were also found, which typically are present in mesenchymal
      tissue but not in lens tissue or capsule. CONCLUSION: Posterior capsular plaques
      in cases of unilateral idiopathic congenital cataract of the AVLID type present a
      protein composition of mainly proteins found in lens epithelial cells and fibres.
      Some proteins however are a specific for lens tissue and are typically seen in
      mesenchymal tissue.

PMID- 30280518
TI  - Influence of CTNNB1 rs2953 polymorphism on schizophrenia susceptibility in
      Chinese Han population through modifying miR-485 binding to CTNNB1.
AB  - Schizophrenia (SCZ) and bipolar disorder (BD) are two major neuropsychiatric
      diseases that are the most substantial causes of disability and mortality
      worldwide. CTNNB1 encodes beta-catenin, an important protein in canonical Wnt
      signaling. We aimed to investigate the association between the rs2953 of CTNNB1
      and the risk of SCZ and BD and to further explore the function of rs2953. A total
      of 1658 samples (548 SCZ cases, 512 BD cases, and 598 controls) were examined in
      terms of the genotype of CTNNB1 rs2953. The mRNA expression level of CTNNB1
      significantly increased in the SCZ and BD groups compared with that in the
      control group. Significant association remained between CTNNB1 3'-untranslated
      region (UTR) variant rs2953 and SCZ susceptibility (additive and dominant model)
      after gender and age were adjusted. rs2953 disrupted the binding of CTNNB1 and
      miR-485. miR-485 significantly suppressed the luciferase activity of CTNNB1-T
      vector by binding to the CTNNB1 3'-UTR containing the T allele of rs2953. The
      mRNA expression of CTNNB1 can be used as a biomarker for the diagnosis of SCZ and
      BD. The 3'-UTR variant rs2953 in CTNNB1 influences the risk of SCZ in the Han
      Chinese population and modifies the binding of miR-485 to CTNNB1.

PMID- 30280519
TI  - Evaluation of vision screening in five- to eight-year-old children living in
      Region Vastra Gotaland, Sweden - a prospective multicentre study.
AB  - PURPOSE: To evaluate the current vision screening criteria regarding amblyopia
      and refractive errors, with emphasis on screening limits and retesting, in Region
      Vastra Gotaland (VGR), Sweden. Visual acuity (VA) screening is performed by
      nurses at primary healthcare centres (PHCs) in 4-year-old children and at school
      in 6- or 7-year-old children. Children with VA <0.65 (>0.19 logMAR) at either eye
      are referred. If VA is 0.65 in one or both eyes, a retest is performed by nurses
      at PHCs and schools, the children are then referred if VA is <0.8 (>0.10 logMAR).
      METHODS: We included all children aged >=5 and <8 years referred between October
      2014 and June 2015 from PHCs and schools to the four eye clinics in VGR, with VA
      >=0.65 in one or both eyes. At the eye clinic, children underwent assessment of
      VA, refraction in cycloplegia, eye motility, cover test, stereo test and a slit
      lamp examination. RESULTS: Among the 259/295 children (139 female) participating,
      median age was 5.7 years (5.0-7.8 years) at referral. Glasses were prescribed due
      to subnormal VA with refractive errors in 20% of the children, 22% displayed
      heterophoria, none had heterotropia and one younger child had amblyopia. Accurate
      retesting gave fewer false-positive referrals. CONCLUSION: Our results showed
      that a vision screening referral cut-off limit of VA <0.65 would leave undetected
      refractive errors. Residual amblyopia was uncommon. Accurate referral criteria,
      retesting and training of those performing the screening as well as re-evaluation
      of the screening programme are all important.

PMID- 30280521
TI  - Subcutaneous Leydig Stem Cell Autograft: A Promising Strategy to Increase Serum
      Testosterone.
AB  - Exogenous testosterone therapy can be used to treat testosterone deficiency;
      however, it has several adverse effects including infertility due to negative
      feedback on the hypothalamic-pituitary--gonadal (HPG) axis. Leydig stem cell
      (LSC) transplantation could provide a new strategy for treating testosterone
      deficiency, but clinical translatability of injecting stem cells inside the
      testis is not feasible. Here, we explore the feasibility of subcutaneously
      autografting LSCs in combination with Sertoli and myoid cells to increase
      testosterone. We also studied whether the grafted LSCs can be regulated by the
      HPG axis and the molecular mechanism behind this regulation. LSCs were isolated
      from the testes of 12-week-old C57BL/6 mice, and subcutaneously autografted in
      combination with Sertoli cells and myoid cells. We found that LSCs alone were
      incapable of self-renewal and differentiation. However, in combination with
      Sertoli cells and myoid cells, LSCs underwent self-renewal as well as
      differentiation into mature Leydig cells. As a result, the recipient mice that
      received the LSC autograft showed testosterone production with preserved
      luteinizing hormone. We found that testosterone production from the autograft was
      regulated by hedgehog (HH) signaling. Gain of function and loss of function study
      confirmed that Desert HH (DHH) agonist increased and DHH antagonist decreased
      testosterone production from autograft. This study is the first to demonstrate
      that LSCs, when autografted subcutaneously in combination with Sertoli cells and
      myoid cells, can increase testosterone production. Therefore, LSC autograft may
      provide a new treatment for testosterone deficiency while simultaneously
      preserving the HPG axis. Stem Cells Translational Medicine 2018.

PMID- 30280522
TI  - Psychological autopsy review on mental health crises and suicide among youth in
      Pakistan.
AB  - INTRODUCTION: Ascertaining putative sociodemographic and clinical causes for
      death by probable suicide can potentially help implement region-specific
      strategies to reduce suicide rates. In this study, we wanted to investigate
      methods utilized and the psychosocial and mental health characteristics of youths
      (aged 12-26 y) who died by probable suicide. METHOD: We examined data from mental
      health clinical files and forensic reports and performed qualitative
      psychological autopsy interview from more than multiple sources for each youth
      who died by probable suicide between 1 May and 31 December 2015 in the Khyber
      Pakhtunkhwa Province of Pakistan. RESULTS: The two most common methods of
      probable suicide were by firearm use and self-poisoning utilizing pesticides that
      were significantly associated with male and female gender, respectively. The most
      common mental health difficulties were major depressive disorder and harmful use
      of psychoactive substances. Other clinical features particularly evident included
      thoughts of self-harm, irritability and aggression, low self-esteem, treatment
      nonadherence, family dispute, and financial distress. CONCLUSION: Efforts to
      reduce the ease of access to firearms and pesticides may potentially have a
      beneficial effect in reducing the suicide rate in this region of Pakistan.

PMID- 30280520
TI  - Generation and characterization of hepatocellular carcinoma cell lines with
      enhanced cancer stem cell potential.
AB  - Hepatocellular carcinoma (HCC) is one of the most common causes for cancer
      related death worldwide with rapidly increasing incidence and mortality rates. As
      for other types of cancers, also in HCC cancer stem cells (CSCs) are thought to
      be responsible for tumour initiation, progression and therapy failure. However,
      as rare subpopulations of tumour tissue, CSCs are difficult to isolate, thus
      making the development of suitable and reliable model systems necessary. In our
      study, we generated HepG2 subclones with enriched CSC potential by application of
      the spheroid formation method and subsequent single-cell cloning. Analyses in
      several 2D and 3D cell culture systems as well as a panel of functional assays
      both in vitro and in vivo revealed that the generated subclones displayed
      characteristic and sustained features of tumour initiating cells as well as
      highly aggressive properties related to tumour progression and metastasis. These
      characteristics could clearly be correlated with the expression of CSC markers
      that might have prognostic value in the clinical HCC setting. Therefore, we
      conclude that our CSC enriched HepG2 clones certainly represent suitable model
      systems to study the role of CSCs during HCC initiation, progression and drug
      resistance.

PMID- 30280523
TI  - Synapse-selective rapid potentiation of hippocampal synaptic transmission by 7,8
      dihydroxyflavone.
AB  - AIM: The identification of 7,8-dihydroxyflavone (DHF) as a small molecule agonist
      for tropomyosin-related kinase B (TrkB) facilitated understanding of the role of
      TrkB signaling in regulating higher brain functions. DHF can penetrate the blood
      brain barrier after systemic administration and changes the performance of
      cognitive and emotional behavioral tasks. However, it is poorly understood how
      DHF modulates neuronal functions at cellular levels. Aiming to understand the
      cellular basis underlying DHF-induced modifications of the brain functions, we
      examined the effects of DHF on the hippocampal excitatory synaptic transmission.
      METHODS: Field excitatory postsynaptic potentials were recorded using hippocampal
      slices prepared from adult male mice. Effects of bath-applied DHF on the synaptic
      efficacy were examined. RESULTS: We found that DHF induced robust synaptic
      potentiation at the mossy fiber to CA3 synapse. DHF had minimal effects at other
      hippocampal excitatory synapses or at immature mossy fiber synapse in juvenile
      mice. The TrkB receptor blockers K252a and ANA-12 did not affect the DHF-induced
      synaptic potentiation. Drug screening revealed that relatively low concentrations
      of 2-aminoethoxydiphenylborane blocked the DHF-induced synaptic potentiation.
      CONCLUSION: Our results demonstrate that DHF selectively potentiates hippocampal
      mossy fiber synaptic transmission via a TrkB receptor-independent mechanism. This
      novel neuromodulatory effect of DHF may influence higher brain functions by
      itself or together with the activation of the TrkB receptor. The rapid induction
      of the potentiation implies its potential importance in the acute behavioral
      effects of DHF.

PMID- 30280524
TI  - The Care Continuum Universe: Delivering on the Promise.

PMID- 30280525
TI  - Strengthening Post-Acute Partnerships: 8 Factors for Success.

PMID- 30280527
TI  - Year in Review: ACHE in 2016.

PMID- 30280526
TI  - Congress Preview: An Interview with Opening Session Speaker Ann Compton.

PMID- 30280529
TI  - Reacquired Memories.

PMID- 30280528
TI  - Rethinking the Traditional Ethics Committee.

PMID- 30280530
TI  - Supporting Patient Dignity, One Outfit at a Time.

PMID- 30280531
TI  - The Election - A New Emphasis on State Innovation.

PMID- 30280532
TI  - Leading a Multigenerational Workforce.

PMID- 30280534
TI  - Ensuring Healthcare Improvements Stick.

PMID- 30280533
TI  - What's your Organization's Value Proposition?

PMID- 30280535
TI  - Developing Front-Line Physician Leaders.

PMID- 30280536
TI  - [Nondestructive Measurement of RDX Grain's Internal Pressure by Using Raman
      Spectrum Method].
AB  - RDX is a most widely used military explosive. As the development of new warheads,
      there are more and more applications of RDX with abnormal grain shapes. To ensure
      the operational effectiveness of the new warheads, it is necessary to find an on
      line nondestructive methods that can measure the RDX grain's internal pressure.
      In this paper, we use Raman spectrum and first-principles methods to determine
      the characteristic spectral line of the RDX samples and have studied the shift of
      the Raman spectral lines under various pressures. In particular, we measured the
      RDX samples under the pressures of 10, 20 and 30 MPa, respectively, and checked
      the fitting errors by measuring the RDX samples under the pressures of 15, 25 and
      35 MPa, respectively. It is found that the shift of the characteristic Raman
      spectral line has a good linear dependence on the external pressures. Therefore,
      we can at first calibrate the linear relation between the shift of the Raman
      spectral line of regular RDX and the pressures in laboratory and then measure the
      Raman spectral line shift of the RDX with abnormal shapes. Based on the
      calibrated linear relation and the measurement of Raman spectra, one can
      determine the internal pressure in RDX. In this way, we can realize the
      nondestructive detection of the internal pressure of RDX. The experiment results
      show that this method has the advantage of good sensitivity and reproducibility.
      The Raman spectrum method has been successfully tested in the warhead production
      line.

PMID- 30280537
TI  - [Fluorescence Properties of Single-Trp Peptide: Response to pH and Metal Ions].
AB  - Considering the important role of metal ions including copper ions are playing in
      human body, a novel single-Trp peptide WDAHSS was designed and synthesized in
      this study to achieve sensitive detection of copper ions via fluorescence
      spectroscopy. The intrinsic fluorescence of a tryptophan residue in WDAHSS, which
      was the only source of the molecular fluorescence, could be easily quenched with
      copper ions. By comparing fluorescence spectra of WDAHSS with those of tryptophan
      molecules at different pH values, the quenching mechanism of WDAHSS was explored
      in detail. Research showed that the histidine in WDAHSS bound copper ions with
      metal coordination. With participation of peptide bond, a square planar structure
      was formed. It was a consequent chelation of copper ions that caused the
      quenching of tryptophan residue. At the same time, this study discussed how pH
      conditions affected the fluorescence spectra of WDAHSS. Furthermore, association
      constants of copper ions towards WDAHSS were calculated through fluorescence
      measurements and fitting analyses. To enhance the anti-jamming ability to pH
      variation, the amino terminal of WDAHSS was intentionally acetylized, leading to
      a stable fluorescence emission under physiological pH conditions. Besides, WDAHSS
      was designed as a special structure to enhance the selectivity and
      biocompatibility of its sensitive detection of copper ions. Further studies on
      WDAHSS may help to improve the fluorescence imaging detection in vivo.

PMID- 30280538
TI  - [Preliminary Study on Atom O in High-Enthalpy Flow Field].
AB  - With Two-photon absorption laser-induced fluorescence(TALIF) technology, leads
      pulse laser in pure high-enthply flow field from the direction of perpendicular
      to flow field, and obtains the two-dimension atom O fluorescent signal with ICCD
      setting outside of test section on the vertical direction of flat made with flow
      field and laser, this signal reflects the relative concentration of atom O. In
      paper, given the experimental environment and experimental equipment, to ensure
      that excitation laser wavelength in experiment is the best one, different angular
      quantum number on ground state of atom O are tested; finally, it is determined
      that J=2, wavelength 225.584 nm shall be experimental excitation laser
      wavelength. To make sure that the obtaining atom O fluorescent signal is in
      unsaturated linear region, in same condition, changing the excitation laser
      energy from small to large to test fluorescent signal, ultimately acquiring laser
      energy linear region is below 3.4 mJ. To record ICCD fluorescent image clearly
      with optimum contrast, Nikon f=105 mm F/2.8 lens is chosen as experimental lens,
      and the results are got with an accumulation of 50 times exposure. By analyzing
      the experimental fluorescent signal, we can get two peak positions on left and
      right of central line about +/-50 mm wide which are generated with compressional
      wave in supersonic flow field, and atom O concentration has 60 mm wide uniform
      area in central zone of subsonic flow field, the concentration decreases
      dramatically. This phenomenon is consistent with flow characteristics of wind
      tunnel, so the method can be applied to flow parameters measurement in the
      future.

PMID- 30280539
TI  - [Separation of Chlorophyll Fluorescence from Scattering Light of Algal Water
      Based on the Polarization Technique].
AB  - Once chlorophyll molecules within the planktonic algae cells absorb light energy,
      they will release energy in the form of chlorophyll fluorescence emission. The
      elastic scattering light of particles in water is partially polarized, while
      chlorophyll fluorescence is unpolarized, so we can use the properties to separate
      the fluorescence signal from total scattering spectra for further retrieval the
      concentration of chlorophyll. But for coastal waters, the approach feasibility is
      still unclear. Based on this, we conducted the experiment in laboratory to
      analyze the influence of different concentrations of inorganic particles (IOP)
      and chlorophyll on the fluorescence extraction using polarization discrimination
      technique. The results indicate that, for algae water with different
      concentrations of IOP, the fluorescence peak will decrease while the
      concentration increase, but the retrieval result is still reliable when the
      concentration up to 300 mg.L(-1). For algae water with different concentrations
      of chlorophyll, the concentration of chlorophyll more higher, the efficiency of
      extracted fluorescence using polarization method is better, for common water,
      this approach can still work. The study proves that the polarization method is
      also applicable for complex water; it is of great importance for further
      detecting the concentration of chlorophyll in coastal waters using remote
      sensing.

PMID- 30280540
TI  - [EROSIVE-ULCERATIVE COMPLICATIONS OF ANTIPLATELET AND/OR ANTICOAGULANT THERAPY IN
      ELDERLY PATIENTS].

PMID- 30280541
TI  - [Application of Two-Dimensional Near-Infrared Correlation Spectroscopy in the
      Specificity Analysis of Noninvasive Blood Glucose Sensing].
AB  - In this paper, two-dimensional (2D) correlation spectroscopy analysis was applied
      to investigate the influence of the main component in blood and the systematic
      drift during the measurement on the specificity of glucose in the near-infrared
      (NIR) spectroscopy. First, the NIR transmittance of glucose aqueous solutions was
      measured and the 2D correlation NIR spectra were calculated under the
      perturbation of glucose concentration. Based on the comparative analysis for
      synchronous and asynchronous 2D correlation spectra, the characteristic
      absorption peaks of glucose in the combination band and the overtone band were
      determined. Then a small amount of albumin was added into glucose aqueous
      solutions, and the transmittance was recorded to perform 2D correlation
      spectroscopy analysis under the perturbation of glucose concentration. However,
      the absorption of glucose in the first overtone band (1590nm) and second overtone
      band (1195nm) was no longer homologous in the 2D correlation spectra, which means
      that the albumin may reduce the specificity of glucose. Further, the oral glucose
      tolerance test of healthy volunteer was conducted and the NIR diffuse reflectance
      of left palm was collected in vivo. The 2D correlation analysis results showed
      that, the homology of glucose in the diffuse reflectance was also destroyed.
      Moreover, as the spectral variation from the glucose concentration change is too
      low to be covered by that induced by systematic drift easily, some background
      correction methods were usually required. For the transmittance experiment of
      glucose aqueous solutions and the diffuse reflectance experiment of human body,
      the pure water sample and 5% diffuse reflectance standard were used as the
      reference, respectively. Then 2D correlation spectroscopy was developed under the
      perturbation of measurement time. Results showed that, smaller band shift was
      observed in the slice spectra of 2D correlation synchronous spectra after the
      corresponding background correction, and the specificity of glucose was improved
      both in the in vitro and in vivo experiments. So for the non-invasive glucose
      sensing by NIR spectroscopy, the wavelengths should be chosen carefully to avoid
      the absorption band of some interfering components which may destroy the homology
      of glucose and make spectral interpretation more complicated. And the selection
      of reference samples for relative measurement is also important to improve the
      specificity of glucose.

PMID- 30280542
TI  - [FEATURES OF HEART RATE VARIABILITY IN PATIENTS WITH ASSOCIATIVE COURSE OF
      GASTROESOPHAGEAL REFLUX DISEASE AND HYPERTENSION].
AB  - The paper presents the results of a study of 83 patients with gastroesophageal
      reflux disease, hypertension and in their comorbidial course. The purpose of the
      study is to examine the characteristics of heart rate variability (HRV) in the
      given cohort of patients. Materials and Methods: The main group consisted of 68
      patients with a mean age of 35,37 +/- 10,34 years. Patients with isolated
      pathologies: 20 - with gastroesophageal reflux disease (GERD), 25 - with arterial
      disease (hypertension) without concomitant diseases. 23 patients had a
      combination of hypertension and GERD. The comparison group consisted of 15
      healthy men. All the subjects were comparable in terms of age, sex, duration of
      Arterial hypertension and GERD. Results: Patients with associated course of
      arterial hypertension and GERD were found to have distinctions in HRV parameters,
      which indicate an increase in sympathetic nervous system activation and a
      decrease in parasympathetic influence. HRV was non-uniform in patients with
      different clinical and endoscopic GERD variants. In patients with endoscopically
      positive GERD (EPRD), there was a significant increase in both time (SDNN, SDANN,
      SDNN-index), and spectral parameters of HRV (VLF, HF). Conclusion: In associated
      course of acid dependent diseases (GERD) and hypertension, time and spectral
      parameters of heart rate variability significantly reduce, reaching the lowest
      values in patients with signs of reflux esophagitis. Comorbidity of GERD and
      hypertension exacerbates originally existing excessive influence of the
      sympathetic nervous system in patients with hypertension, leading to
      parasympathetic failure, and, ultimately, significantly weakening adaptive
      capabilities. Revealed changes in HRV parameters among patients with the given
      sintropy defines such a combination of diseases as undesirable, both for
      cardiovascular and autonomic nervous systems.

PMID- 30280543
TI  - [ROLE OF TGFbeta-INDUCTION AND GASTROINTESTINAL MYOFIBROBLASTS IN
      PATHOMORPHOGENESIS OF CHRONIC GASTRITIS IN PATIENTS WITH MARFAN SYNDROME AND
      MARFAN-LIKE STATES].
AB  - Aim: The aim was to explore the features of epithelial morphogenesis and
      reparation of gastric mucosa in chronic gastritis in patients with Marfan
      syndrome and Marfan -like states. Materials and methods: A histological
      evaluation and immunohistochemical analysis of the expression of antibodies
      against alpha-actin smooth muscle (alpha-SMA), collagen type III and transforming
      growth factor beta (TGFbeta) in the gastric mucosa in 50 patients with hereditary
      disorders of connective tissue between the ages of 17 to 41 years were performed.
      Results: In patients with Marfan syndrome and marfan-like states chronic
      gastritis was an unfavorable factor for the progression of the background
      atrophic and fibrotic processes in the gastric mucosa. It proved a key role
      disinhibited to TGFbeta activity-dependent activation of fibrogenesis of
      subepithelial myofibroblasts (alpha-SMA +) with the development of a special
      morphogenetic variants of early chronic atrophic multifocal gastritis at a young
      age.

PMID- 30280544
TI  - [Online Analysis of Dynamic Trend Regression and Endpoint Determination for
      Chinese Traditional Medicine Extraction Process Based on Ultraviolet
      spectroscopy].
AB  - With the transition of Chinese traditional medicine manufacture industry,
      modernization has become the inexorable tendency in its future development.
      However, during the current Chinese traditional medicine producing process, the
      lack of online monitoring leads to the lagging of quality detection, as well as
      quality differences between products. In this paper, aiming at realizing online
      monitoring and end point automatic determination for Chinese traditional medicine
      (CTM) extraction unit, which is one of the most important units in CTM producing,
      ultraviolet (UV) spectroscopy is applied to build UV absorbance dynamic model
      based on the Lambert-Beer law and the CTM extraction kinetic model which presents
      a new method of UV absorbance dynamic analysis and endpoint determination,
      including curve regression, robustness analysis and endpoint calculation. In the
      experiment for online monitoring homalomena occulta extraction, the online UV
      spectral collection system for CTM extraction, developed by our laboratory, was
      applied for spectral collection; meanwhile, solid component contents in the
      offline samples were measured as reference. During the analysis, first of all, we
      pretreated the spectrum collected in the current period with interpolation and
      smoothing, and calculated the mean value within a UV region of 230.2~400 nm to
      form an absorbance mean value sequence with data obtained in the early
      measurements; then we verified the linear correlation between the sequence of
      absorbance and the concentrations of effective component in the solution, the
      linear correlation coefficient equals 0.982 8, showing a high linearity between
      UV spectra and solid component contents; finally, we regressed the absorbance
      mean value sequence with the dynamic model, analyzing its robustness and the
      extraction endpoint. Experimental results demonstrate that, the robustness
      analysis could recognize the bad points of measurement during the regression
      process, and improve the consistency between the regression and the original
      curves, raising its squared correlation coefficient to more than 0.99; meanwhile,
      with endpoint determination, we shortened the homalomena occulta extraction
      process from the original manually set 180 to 122 min effectively. The experiment
      above proves that this method with UV spectroscopy realizes online monitoring and
      automatic endpoint determination for the CTM extraction process, and is of
      significant importance for stabilizing production as well as improving economic
      benefit.

PMID- 30280545
TI  - [CLINICAL CHARACTERISTICS OF PATIENTS WITH ARTERIAL HYPERTENSION ASSOCIATED WITH
      PEPTIC DUODENAL ULCER AFTER ACUTE GASTROINTESTINAL BLEEDING].
AB  - Objective of the investigation was to examine clinical characteristics of peptic
      duodenal ulcer (DU) associated with arterial hypertension (AH) after acute
      gastrointestinal bleeding (AGB). The study included 25 patients with AH
      associated with DU, 45 patients with AH in AGB, 63 patients with AGB without AH,
      48 patients with AH without AGB and 69 patients with DU without AH. If AH joins
      the existing DU, it increases the intensity of pain and dyspeptic syndromes. If
      DU joins AH, on the other hand, the clinical picture of ulcer disease was
      unclear. The largest concentration of Helicobacter pylori antibodies was found in
      patients with AH in AGB. Hypertensive crises were detected more often in
      combination of AH and DU.

PMID- 30280546
TI  - [Multi-Spectrum CT Imaging Method Based on Spectrum Matching Priors].
AB  - In the process of X-ray computed tomography (CT) imaging, the traditional single
      energy X-ray CT imaging technology is only applicable to structural analysis but
      can't meet the needs of functioning for substance distinction and identification
      because of the multispectral hardening artifacts and inconsistency between the
      projection acquisition process and reconstruction assumption. A multispectral CT
      imaging method based on the spectrum matching priors is presented. First, energy
      spectrum filtering matching model is built and range spectrum parameters are set
      according to the material composition; then multi-spectrum projection sequence is
      acquired by filtering. Second, the different reference energy is selected
      according to the material composition, befor using the improved Algebraic
      Reconstruction Techniques (ART) to achieve a multi-spectral CT imaging.
      Simulation result shows that we improved the contrast of the reconstructed image
      effectively, while meeting the needs of substance distinction. The actual data
      collection process is achieved by reconstructing in different spectrum and
      different corresponding reference energy.

PMID- 30280547
TI  - [ULCER DAMAGE TO THE GASTROINTESTINAL PATH ASSOCIATED WITH HYPERTENSION AS A
      MANIFESTATION OF COMORBIDITY AMONG RAILWAY WORKERS].
AB  - Purpose of the study: The investigation of clinical and laboratory parameters
      that characterize the pathogenetic connections of association of ulcerative
      lesions of the gastrointestinal tract and hypertension as work-related diseases
      among workers of locomotive brigades. Materials and methods: 192 railway workers
      were examined. The level of general clinical and biochemical parameters in the
      blood serum were investigated. Results: Due to the syntopy of duodenal ulcers and
      (or) the stomach and hypertension on the background of the negative impact of
      harmful factors of production the abnormalities in the vascular endothelium with
      signs of systemic inflammation are revealed. Conclusion: The identified
      parameters can be considered as an early predictor of formation of hypertension
      as well as a comorbid flow of duodenal ulcers and (or) of the stomach and
      hypertension, assessing it as work-related diseases.

PMID- 30280548
TI  - [CHRONIC PANCREATITIS AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE: CLINICAL ASPECTS
      OF COMORBIDITY].
AB  - Objective: To identify chronic obstructive pulmonary disease (COPD) features of
      the clinical manifestations in patients with chronic pancreatitis (CP). Materials
      and methods: 67 patients with comorbidity of CP and COPD (main group), 54 - with
      isolated COPD (compared group) have been examined. Assessment of clinical
      symptoms severity was perfomed by Modified Medical Research Council (mMRC)
      Dyspnea Scale and a 4-point scale of COPD patients symptoms (P. L. Paggiaro).
      Integral assessment of the impact of COPD on patient was conducted in accordance
      with the GOLD guidelines (2015). Results: It has been found out that patients
      with comorbid pathology are characterized by the significant increase rate of
      infectious exacerbation of COPD than in the compared group: 67.2% vs. 48.1% (p =
      0.03). The seasonal nature of COPD exacerbation was observed in isolated COPD in
      88.9% of cases, in comorbid pathology - 73.1% (p = 0.03). In compared group 1,4
      +/- 0,2 exacerbations per year were recorded, in patients of the main group - 2,3
      +/- 0,4 (p = 0.03). Severity of dyspnea in patients of the main group was 2,4 +/-
      0,5 points, in compared group - 2,1 +/- 0,6 points (p = 0.03). The expressiveness
      of cough in isolated COPD made up to 2,3 +/- 0,4 points, while comorbid disease -
      2,6 +/- 0,5 points (p = 0.03). Intensity of sputum in patients of the main group
      reached 1,7 +/- 0,6 points, in compared group 1,6 +/- 0,7 points (p = 0.66).
      Integral assessment of the COPD impact on patient (GOLD, 2015) showed that the
      distribution of patients with comorbid pathology by groups of risk had a
      significant difference from the one in the compared group (df = 2, chi2 = 14,201,
      p < 0.001). Conclusions: The presence of concomitant chronic pancreatitis in
      patients with COPD brings in a certain deviation in the clinical characteristics
      of the disease: significantly more often as a trigger were acute respiratory
      viral infections, less pronounced seasonal nature of exacerbations, significantly
      increasing the number of exacerbations per year, a significant increase of
      dyspnea, cough and changes of sputum. Carrying out the integrated assessment of
      the impact of COPD on patient it has been observed that redistribution of main
      group patients into risk groups in the side of its aggravation.

PMID- 30280549
TI  - [ROLE OF C-REACTIVE PROTEIN AND TUMOR NECROSIS FACTOR-alpha IN IMMUNOREGULATION
      SYSTEM IN PATIENTS WITH CONCOMITANT COURSE OF CHRONIC PANCREATITIS AND TYPE 2
      DIABETES MELLITUS].
AB  - Purpose: To determine the content of markers of inflammation, namely C-reactive
      protein and tumor necrosis factor-alpha in patients with combined course of
      chronic pancreatitis and type 2 diabetes mellitus. Materials and methods: The
      investigation involved of 20 patients with isolated chronic pancreatitis and 20
      patients with combined course of chronic pancreatitis and type 2 diabetes
      mellitus. The control group consisted of 20 healthy individuals. Results: It was
      found that patients with combined course of chronic pancreatitis and type 2
      diabetes had significantly higher levels of C-reactive protein and hyper-TNF
      alpha-emia (p < 0.05). Patients of all study groups revealed a close correlation
      between C-reactive protein and tumor necrosis factor-alpha (p < 0.05)/
      Conclusions: The results of the study suggest that the levels of C-reactive
      protein and tumor necrosis factor-alpha are important diagnostic markers of
      inflammation in patients with chronic pancreatitis and type 2 diabetes mellitus.

PMID- 30280550
TI  - [PREDICTION OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEART FAILURE AND
      METABOLIC SYNDROME].
AB  - : Currently, the non-alcoholic fatty liver disease (NAFLD) is recognized as the
      most common chronic liver disease. 27.8% of patients with NAFLD have diseases of
      the cardiovascular system (cardiovascular), which are the leading cause of death
      in patients with NAFLD. Objective: To study the probability of liver fibrosis in
      patients with metabolic syndrome and chronic heart failure (CHF). Materials and
      Methods: The study included 77 patients with CHF. The diagnosis of CHF was
      confirmed by the qualitative measurement of NT-proBNP. The severity of the
      clinical manifestations of heart failure, functional status of the patient was
      assessed. All patients underwent clinical and biochemical blood tests, ECG,
      ultrasound examination of the liver. The size of the heart chambers, wall
      thickness of the myocardium and epicardial fat were evaluated by
      echocardiography. The NAFLD Fibrosis Score (NFS) was calculated in all patients
      enrolled in the study. Results: In the study group patients The direct
      correlations between the value of NFS: weight (r = 0,38; p = 0,001), glucose
      levels (r = 0,54; p = 0,001), the level of glycosylated hemoglobin (r = 0,51; p =
      0,002), LV myocardium mass (r = 0, 51; p = 0,005), the sizes of the right atrium
      (RA) (r = 0,45; p = 0,013), sizes of the left atrium (LA) (r = 0,41; p = 0,023)
      were found in the study group patients. Inverse correlation between the value of
      NFS: total cholesterol (r = -0,43; p = 0,008), epicardial fat thickness (EFT) (r
      = 0,29; p = 0,014), end-diastolic (CD) left ventricular size (r = 0,27; p =
      0,02), end-systolic (CS), left ventricular size (r = 0,27; p = 0,02), CD
      ventricular volume (r = 0,25; p = 0,02), CS LV volume (r = 0,28; p = 0,02). NFS
      is correlated with the six-minute walk test (6MWT) (p = 0,023; U-Mann-Whitney).
      Using the NAFLD fibrosis score in internist routine practice help to identify
      patients with NAFLD and cardiovascular diseases by non-invasive way in the early
      stages of the disease and to adjust the current treatment, if necessary.

PMID- 30280551
TI  - [Rapid Determination of Dodecylmorpholine in Aqueous Solutions with UV-Vis
      Spectrophotometry].
AB  - A rapid UV-Vis spectrophotometric method was proposed to determine the
      concentration of DMP in aqueous solutions. The linear concentration range of DMP
      solution at the range of 250~400 nm is 0.5~70 mmol.L(-1). At 275 nm, the linear
      fitting equation is A=0.030 7c+0.133 0 with a correlation of 0.980 9. The
      detection limitation is 9.46*10-5 mmol.L-1, the RSD (n=6) of the method were at
      the range of 0.100%~0.612%. The recovery ratio for salt solutions sample is
      95%~104%. Temperature, pH, and coexisting K(+), Na(+), Mg(2+), Cl(-), Br(-), I(
      ), SO(2-)(4) ions do not affect the detection. The coexisting CO(2-)(3) and HCO(
      )(3) ions can be eliminated with acidification. The results showed that the
      proposed method is simple in pretreatment process and has high accuracy and
      precision. It is a quick measurement method of DMP concentration in water
      solution, and can be used to measure DMP concentration in reverse flotation tail
      liquid and reverse flotation material pulp.

PMID- 30280552
TI  - [CLINICAL EFFICACY OF THE RECEPTOR BETA AND ALPHA BLOCKERS - CARVEDILOL AND
      ORNITHINE-ASPARTATE IN PATIENTS WITH CHD AND CHF COMBINED WITH ALCOHOLIC LIVER
      DISEASE].
AB  - Aim: The aim of the paper is to study the clinical efficacy of carvedilol and
      ornithine-aspartate in the complex therapy (ACE inhibitors, diuretics, cardiac
      glycosides, nitrates indication), to assess their impact on quality of life,
      intracardiac hemodynamics, remodeling of the left (LV) and right ventricular
      (RV), indicators of the inflammatory enzyme activity in blood serum of patients
      with coronary heart disease with CHF II-III FC and alcoholic liver disease (ALD).
      Materials and Methods: 95 patients were studied 45-75 years (mean age - 58,2 +/-
      1,2) with CHF II-III FC and postinfarction cardiosclerosis, LVEF less than 45%.
      ALD was diagnosed in 58 patients. In 23 (39%) patients among them had steatosis,
      18 (30.5%) - chronic hepatitis (CH), 17 (30.5%) - liver cirrhosis (LC). Patients
      were divided into 3 groups. Patients in the first group (37 people) with coronary
      artery disease and heart failure without a UPS received an average dose of
      carvedilol in - 32,8 +/- 4,7 mg / day. Patients in the 2nd group (32 persons)
      suffering from coronary artery disease, heart failure, and UPS received
      carvedilol in an average dose of 25,4 +/- 1,6- mg / day and L-ornithine-L
      aspartate in a dose of 10 g granulate per day for 2 weeks, and then by 5g a day
      for 4 months. Patients in the third control group (26 people) with CHD and CHF
      and CHF ABP received basic therapy (without beta-blocker) and ademetionine at a
      dose of 800 mg / day for 2 weeks, followed by 400 mg / day for 4 months. Results:
      After 4 months of observation, it was noted that CHF patients with IHD in
      combination with BPO flows less favorably. In all groups, the clinical status of
      patients was improved on the background of the therapy, however, the clinical
      status was more pronounced while using carvedilol and ornithine-aspartate (Group
      2): summary measure of quality of life has improved by 38 points, the speed of
      the test increased with a digital sequence up to 54.4, decreased shortness of
      breath, edema, ascites, portal hypertension effects, hepatocellular insufficiency
      and hepatic encephalopathy. In general, was shown the normalization of sleep
      rhythm, reducing sleepiness, improved memory, attention, reduced asterixis and
      sweeping hand tremor, asthenia. Conclusions: The use of carvedilol and ornithine
      aspartate in the treatment of patients with CHF FC II-III with CHD and BPO
      improves the clinical condition of patients, quality of life, hemodynamics,
      reduces the severity of pulmonary hypertension and normalizes serum biochemical
      parameters.

PMID- 30280553
TI  - [LIPID PROFILE AND LIVER DISEASES AMONG PATIENTS WITH MORBID OBESITY].
AB  - Objectives: The aim of our study was to investigate associations between the
      lipid profile, liver condition and the level of BMI. Methods: Our sample
      consisted of 58 patients: 30 - with morbid obesity and BMI - 40-49 (1 group), 28 
      with superobesity, BMI - 50-69 (2 group). Lipids and hepatic functional tests
      were measured just prior to surgery. Ultrasound examination was used to estimate
      liver condition. Liver biopsy specimens were obtained at the time of surgery,
      classified according to the nonalcoholic fatty liver disease and steatohepatitis
      activity score. Results: Lower level of cholesterol has been found in the first
      group with morbid obesity. Higher level of triglycerides and very low-density
      lipoprotein has been found in the second group with superobesity (r=0,000 ANOVA).
      High-density lipoprotein was normal but significantly associated with BMI. The
      level of low-density lipoprotein was higher in the second group, but the
      difference between ptoups was not significant. BMI was associated with higher
      scores of ultrasonographic parameters and severity of steatosis, the increased
      prevalence of steatohepatitis and it activity. We also realized the positive
      correlation between ultrasonographic parameters and histological features.
      Conclusion: BMI has significantly positive correlations with the level of
      triglycerides and very low-density lipoprotein, ultrasonographic parameters,
      histological features of steatosis and steatohepatitis. The level of total
      cholesterol did not reflect all changes of lipid profile.

PMID- 30280554
TI  - [DISLIPOPROTEINEMIA AND HEPATOTOXICITY - OCCUPATIONALLY RELATED PATHOLOGY IN
      WORKERS OF CHEMICAL PRODUCTION].
AB  - The article discusses the development of occupational pathologies of the
      digestive system and it is associated with dyslipidemia. Selected the most
      informative indicators for timely identification of metabolic "targets" of damage
      in workers in chemical production of methanol.

PMID- 30280556
TI  - [CLINICAL FEATURES DURING THE ACUTE CHOLECYSTITIS IN THE OLDER AGE GROUP OF
      PATIENTS].
AB  - One of the most popular abdominal diseases is an acute cholecystitis. that's why
      is very actual in acute cholecystitis the study of clinical features in the older
      age group of patients in improving of preoperative diagnosis and adequate option
      of treatment. In the research were involved 1273 patients, wiich were the
      patients during 2007-2014 years in Medical center of Yerevan, department of
      Laporacopic surgery, who suffered from acute cholecystitis. Research findings
      from the data analysis allows us to assume that the characteristics of the older
      age group of patients during the acute cholecystitis are difficult to do some
      surgical intervention and it needs very clever prediction for treatment.

PMID- 30280555
TI  - [DISBIOTIC AND IMMUNOLOGICAL CHANGES OF PATIENTS WITH CHRONIC OBSTRUCTIVE
      PULMONARY DISEASE AND ITS COMBINATION WITH ARTERIAL HYPERTENSION].
AB  - Studied indicators microflora and immune parameters in 75 patients with chronic
      obstructive pulmonary disease (COPD). Of these, 54 - COPD with arterial
      hypertension, at 21-isolated leaking COPD. The degree of dysbiosis evaluated on
      caseinolitic activity feces, immune status - by performance of leukogram and
      immunograms at determining the levels of CD3+-, CD4+-, CD8+-, CD19+-cells, Ig A,
      Ig M, Ig G, NST-test. For most COPD patients with hypertension compared with
      patients with COPD characterized by more pronounced dysbiosis, inflammatory
      syndrome, the weakening of the functioning of cellular immunity, increased
      tension of humoral immunity and changed reactions in phagocytic immunity.
      Disbiotic and immune changes increase with increasing the degree of hypertension
      from I to III.

PMID- 30280557
TI  - [SOME PECULIARITIES OF ENDOSCOPIC ANATOMY OF THE GASTRODUODENAL TRANSITION AND
      ITS CHANGES IN DUODENAL PEPTIC ULCER].
AB  - Objective: To improve the diagnosis of the diseases of the pylorus and prepyloric
      region in patients with duodenal peptic ulcer based on the study of the mucous
      membrane folds Materials and methods: Endoscopic examination of 208 patients
      without diseases of the gastroduodenal transition (healthy) and 112 patients with
      duodenal peptic ulcer of three age groups from 35 to 90 years. Men were 72 and
      61, women - 136 and 51 respectively groups. Endoscopic examinations were
      performed by endoscopes EVIS GIF-130, XP-150 N, GIF H-180 and instruments of the
      company "Olympus" (Japan). Results: Individual differences were revealed in the
      formation of mucous membrane folds of the pylorus and prepyloric region, in the
      frequency of participation of the walls in healthy people and patients with
      duodenal peptic ulcer. Age differences were revealed. Gender differences were not
      revealed. The clinical case of the patient with duodenal peptic ulcer and maltoma
      in prepyloric region was presented. Conclusion: The features of the formation of
      mucous membrane folds, the relief of the mucous membrane of the pylorus and
      prepyloric region in healthy people and patients with peptic ulcer of the
      duodenum are necessary to consider. It is important to perform a biopsy,
      histological, c.

PMID- 30280558
TI  - Interface Design Strategy for the Fabrication of Highly Stretchable Strain
      Sensors.
AB  - Simultaneously achieving high piezoresistive sensitivity, stretchability, and
      good electrical conductivity in conductive elastomer composites (CECs) with
      carbon nanofillers is crucial for stretchable strain sensor and electrode
      applications. Here, we report a facile and environmentally friendly strategy to
      realize these three goals at once by using branched carbon nanotubes, also known
      as the carbon nanostructure (CNS). Inspired by the brick-wall structure, a robust
      segregated conductive network of a CNS is formed in the thermoplastic
      polyurethane (TPU) matrix at a very low filler fraction, which renders the
      composite very good electrical, mechanical, and piezoresistive properties. An
      extremely low percolation threshold of 0.06 wt %, currently the lowest for TPU
      based CECs, is achieved via this strategy. Meanwhile, the electrical conductivity
      is up to 1 and 40 S/m for the composites with 0.7 and 4 wt % CNS, respectively.
      Tunable piezoresistive sensitivity dependent on CNS content is obtained, and the
      composite with 0.7 wt % filler has a gauge factor up to 6861 at strain epsilon =
      660% (elongation at break is 950%). In addition, this strategy also renders the
      composites' attractive tensile modulus. The composite with 3 wt % CNS shows 450%
      improvement in Young's modulus versus neat TPU. This work introduces a facile
      strategy to fabricate highly stretchable strain sensors by designing CNS network
      structures, advancing understanding of the effects of polymer-filler interfaces
      on the mechanical and electrical property enhancements for polymer
      nanocomposites.

PMID- 30280559
TI  - Fabrication of Strain Gauges via Contact Printing: A Simple Route to Healthcare
      Sensors Based on Cross-Linked Gold Nanoparticles.
AB  - In this study, we developed a novel and efficient process for the fabrication of
      resistive strain gauges for healthcare-related applications. First, 1,9
      nonanedithiol cross-linked gold nanoparticle (GNP) films were prepared via layer
      by-layer (LbL) spin-coating and subsequently transferred onto flexible polyimide
      foil by contact printing. Four-point bending tests revealed linear response
      characteristics with gauge factors of ~14 for 4 nm GNPs and ~26 for 7 nm GNPs.
      This dependency of strain sensitivity is attributed to the perturbation of charge
      carrier tunneling between neighboring GNPs, which becomes more efficient with
      increasing particle size. Fatigue tests revealed that the strain-resistance
      performance remained nearly the same after 10.000 strain/relaxation cycles. We
      demonstrate that these sensors are well suited to monitor muscle movements.
      Furthermore, we fabricated all-printed strain sensors by directly transferring
      cross-linked GNP films onto soft PDMS sheets equipped with interdigitated
      electrodes. Due to the low elastic modulus of poly(dimethylsiloxane) (PDMS),
      these sensors are easily deformed and, therefore, they respond sensitively to
      faint forces. When taped onto the skin above the radial artery, they enable the
      well-resolved and robust recording of pulse waves with diagnostically relevant
      details.

PMID- 30280561
TI  - A Method for the Preparation of Highly Oriented MAPbI3 Crystallites for High
      Efficiency Perovskite Solar Cells to Achieve an 86% Fill Factor.
AB  - The quality of the perovskite absorber is known to be the most crucial parameter
      for the photovoltaic performance of perovskite solar cells. By combining the one
      step anti-solvent engineering method followed by gas blowing, MAPbI3 film
      containing highly oriented multi-crystalline nanograins (150~500 nm) was made
      first. A user-friendly, simple, large-throughput, and reproducible post-solvent
      annealing (made by treating the film with anti-solvent containing H2O under
      spinning) was used to enlarge the perovskite grains up to 1.5 MUm. Inverted (p-i
      n) perovskite solar cells based on this highly ordered, large-grain MAPbI3 film
      achieve the highest efficiency of 21% with an extremely high fill factor (FF) of
      86%. The high-efficiency cell shows almost no current hysteresis and is stable
      under 1 sun illustration in a glovebox or standing in the ambient atmosphere
      (20~25  degrees C, ca. 30% humidity) under room lighting (T5 lamp, 500 lux). A
      creative method combining the gas blowing with quick and simple post-treatment to
      prepare a highly oriented MAPbI3 film with large multi-crystalline grains to
      achieve excellent photovoltaic performance was demonstrated. This creative film
      preparation method was also successfully applied to fabricate large area MAPbI3
      film for high-efficiency perovskite mini-modules. Being able to control the
      crystallization and growth of perovskite crystallites definitely makes the
      fabrication of perovskite solar cells more reproducible.

PMID- 30280560
TI  - Polarity Control within One Monolayer at ZnO/GaN Heterointerface: (0001) Plane
      Inversion Domain Boundary.
AB  - In semiconductor heterojunction, polarity critically governs the physical
      properties, with an impact on electronic or optoelectronic devices through the
      presence of pyroelectric and piezoelectric fields at the active heteropolar
      interface. In the present work, the abrupt O-polar ZnO/Ga-polar GaN
      heterointerface was successfully achieved by using high O/Zn ratio flux during
      the ZnO nucleation growth. Atomic-resolution high-angle annular dark-field and
      bright-field transmission electron microscopy observation revealed that this
      polarity inversion confines within one monolayer by forming the (0001) plane
      inversion domain boundary (IDB) at the ZnO/GaN heterointerface. Through
      theoretical calculation and topology analysis, the geometry of this IDB was
      determined to possess an octahedral Ga atomic layer in the interface, with one
      O/N layer symmetrically bonded at the tetrahedral site. The computed electronic
      structure of all considered IDBs revealed a metallic character at the
      heterointerface. More interestingly, the presence of two-dimensional (2D) hole
      gas (2DHG) or 2D electron gas (2DEG) is uncovered by investigating the chemical
      bonding and charge transfer at the heterointerface. This work not only clarifies
      the polarity control and interfacial configuration of the O-polar ZnO/Ga-polar
      GaN heterojunction but, more importantly, also gives insight into their further
      application on heterojunction field-effect transistors as well as hybrid ZnO/GaN
      optoelectronic devices. Moreover, such polarity control at the monolayer scale
      might have practical implications for heterojunction devices based on other polar
      semiconductors.

PMID- 30280562
TI  - Cathodic Quantum Dot Facilitated Electrochemiluminescent Detection in Blood.
AB  - The expansion of electrochemical sensors to biomedical applications at point of
      care requires these sensors to undergo analysis without any pretreatment or
      extraction. This poses a major challenge for all electrochemical sensors
      including electrochemiluminescent (ECL)-based sensors. ECL offers many advantages
      for biomedical applications; however, obtaining results from complex matrixes has
      proven to be a large hurdle for the application of ECL sensors within this field.
      This work demonstrates the potential of cathodic ECL to detect and quantify
      homocysteine (Hcy) with a 0.1 nM limit of detection, which is associated with
      hyperhomocysteinemia, in blood. This near-infrared quantum dot (NIR QD)-based ECL
      sensor displays good linearity allowing for rapid detection and providing a basis
      for exploitation of ECL-based sensors for biomedical diagnostics utilizing Hcy as
      a model cathodic coreactant. This work will lay the foundations for future
      developments in biosensing and imaging fields and stands as an initial proof of
      concept for the utilization of cathodic ECL technologies for biomedical
      applications once the limits of detection within clinically relevant levels has
      been achieved. This work illustrates the potential of cathodic ECL sensors, using
      Hcy as a model complex, for the detection of biomolecules.

PMID- 30280563
TI  - Construction of Highly Hierarchical Layered Structure Consisting of Titanate
      Nanosheets, Tungstate Nanosheets, Ru(bpy)32+, and Pt(terpy) for Vectorial
      Photoinduced Z-Scheme Electron Transfer.
AB  - To imitate the precisely ordered structure of the photoantennas and electron
      mediators in the natural photosynthesis system, we have constructed the
      Ru(bpy)32+-intercalated alternate-layered structure of titanate nanosheets and
      tungstate nanosheets via thiol-ene click reaction. Before nanosheet stacking,
      Pt(terpy) was immobilized at the edge of the titanate nanosheets. The visible
      light-induced vectorial Z-scheme electron transfer reaction from the valence band
      of tungstate to the conduction band of titanate via the photoexcited Ru(bpy)32+
      was demonstrated by the following two evidences: (1) From the results of the
      fluorescence decay of Ru(bpy)32+, the rate of the forward electron transfer from
      the photoexcited Ru(bpy)32+ to the conduction band of titanate was estimated as
      1.16 * 108 s-1, which was 10 times faster than the backward electron transfer
      from the photoexcited Ru(bpy)3 to the conduction band of tungstate (1.02 * 107 s
      1) due to a localization of Ru(bpy)32+ on the titanate nanosheets. (2) We
      observed the decrease of the electrons accumulated in the conduction band of the
      tungstate induced by photoexcitation of Ru(bpy)32+, demonstrating the forward
      electron transfer from the conduction band of tugnstate to the vacant highest
      occupied molecular orbital level of the photoexcitation Ru(bpy)32+. Finally, H2
      gas was produced from the water dispersion of the alternate-layered structure
      under visible light irradiation, suggesting that the electrons getting to the
      conduction band of the titanate were transferred to the Pt(terpy) placed at the
      edge of the nanosheets, and reduced water to dihydrogen. Herein, n-octylamine
      species at the interlayer space played a role as hole scavenger; in other words,
      these molecules were oxidized by the hole in the conduction band of the tungstate
      nanosheets.

PMID- 30280564
TI  - ReaxFF Molecular Dynamics Study on the Influence of Temperature on Adsorption,
      Desorption, and Decomposition at the Acetic Acid/Water/ZnO(1010) Interface
      Enabling Cold Sintering.
AB  - The reaction dynamics of a liquid-solid interface with the example of an acetic
      acid/water solution interacting with a ZnO(1010) surface was investigated using
      ReaxFF reactive force field-based molecular dynamics. The interactions were
      studied over a broad temperature range to assess the kinetics and reaction
      pathways. Two different acetic acid dissociation mechanisms are observed in the
      simulations: (1) deprotonation to surface cation, which produces a terminal
      hydroxyl and (2) deprotonation to a bridging hydroxyl, which results in water
      production. An increase in temperature promotes the dissociation of acetic acids
      and its adsorption to surface at first, but as the temperature increase
      continues, the surface coverage by acetates decreases due to evaporation from the
      surface or decomposition. The acetate decomposition starts with a nucleophilic
      attack of oxygen to methyl carbon and results in the production of carbon
      dioxide, which is consistent with experimental findings in the literature. The
      coverage of the surface by water molecules decreases as the system is heated up,
      which is also observed in other molecular dynamics studies. At elevated
      temperatures, acetate molecules are more stable than water molecules or bridging
      hydroxyls on the surface. These simulations validate the ReaxFF method for the
      water/organic mixture and metal oxide surface interactions and provide insights
      into structure and reactivity of aqueous solvents on metal oxide surfaces at
      elevated temperatures. Adsorption trends that are observed in this study are
      consistent with phenomenological Langmuir models. The reaction of acetic acid
      decomposition to smaller molecules such as CO2 and CH2O agrees with experimental
      observations. Understanding the details of these dynamic surface reactions are
      critical to understand important new cold sintering processes that utilize
      transient liquid and solid reactions, and the latter could be used to predict
      solvent selection for cold sintering.

PMID- 30280565
TI  - Enhanced Environmental Stability Coupled with a 12.5% Power Conversion Efficiency
      in an Aluminum Oxide-Encapsulated n-Graphene/p-Silicon Solar Cell.
AB  - A significant improvement in the power conversion efficiency (PCE) and the
      environmental stability of n-Graphene/p-Si solar cells is indicated through
      effective n-doping of graphene, using low work function oxide capping layers. AlO
      x, deposited through atomic layer deposition, is particularly effective for such
      doping and in addition serves as an antireflection coating and a cell
      encapsulating layer. It is shown that the related charge transfer doping and
      interfacial engineering was crucial to achieve a record PCE of 12.5%. The work
      indicates a path forward, through work function engineering, for further
      efficiency gains in Gr-based solar cells.

PMID- 30280567
TI  - The Muscarinic Acetylcholine Receptor M5: Therapeutic Implications and Allosteric
      Modulation.
AB  - The muscarinic acetylcholine receptor (mAChR) subtype 5 (M5) was the most recent
      mAChR to be cloned and has since emerged as a potential therapeutic target for a
      number of indications. Early studies with knockout animals have provided clues to
      the receptor's role in physiological processes related to Alzheimer's disease,
      schizophrenia, and addiction, and until recently, useful subtype-selective tools
      to further probe the pharmacology of M5 have remained elusive. Small-molecule
      allosteric modulators have since gained traction as a means by which to
      selectively examine muscarinic pharmacology. This review highlights the discovery
      and optimization of M5 positive allosteric modulators (PAMs) and negative
      allosteric modulators (NAMs).

PMID- 30280566
TI  - Nonenzymatic Polymerization into Long Linear RNA Templated by Liquid Crystal Self
      Assembly.
AB  - Self-synthesizing materials, in which supramolecular structuring enhances the
      formation of new molecules that participate to the process, represent an
      intriguing notion to account for the first appearance of biomolecules in an
      abiotic Earth. We present here a study of the abiotic formation of interchain
      phosphodiester bonds in solutions of short RNA oligomers in various states of
      supramolecular arrangement and their reaction kinetics. We found a spectrum of
      conditions in which RNA oligomers self-assemble and phase separate into highly
      concentrated ordered fluid liquid crystal (LC) microdomains. We show that such
      supramolecular state provides a template guiding their ligation into hundred
      bases long chains. The quantitative analysis presented here demonstrates that
      nucleic acid LC boosts the rate of end-to-end ligation and suppresses the
      formation of the otherwise dominant cyclic oligomers. These results strengthen
      the concept of supramolecular ordering as an efficient pathway toward the
      emergence of the RNA World in the primordial Earth.

PMID- 30280568
TI  - Single-Molecule Kinetic Investigation of Cocaine-Dependent Split-Aptamer
      Assembly.
AB  - Aptamers are short nucleic-acid biopolymers selected to have high affinity and
      specificity for protein or small-molecule target analytes. Aptamers can be
      engineered into split-aptamer biosensors comprising two nucleic acid strands that
      coassemble as they bind to a target, resulting in a large signal change from
      attached molecular probes (e.g., molecular beacons). The kinetics of split
      aptamer assembly and their dependence on target recognition are largely unknown;
      knowledge of these kinetics could help in design and optimization of split
      aptamer biosensors. In this work, we measure assembly kinetics of cocaine
      dependent split-aptamer molecules using single-molecule fluorescence imaging.
      Assembly is monitored between a DNA strand tethered to a glass substrate and
      solutions containing the other strand tagged with a fluorescent label, with
      varying concentrations of the cocaine analyte. Dissociation rates are measured by
      tracking individual molecules and measuring their bound lifetimes. Dissociation
      time distributions are biexponential, possibly indicating different folded states
      of the aptamer. The dissociation rate of only the longer-lived complex decreases
      with cocaine concentration, suggesting that cocaine stabilizes the long-lived
      aptamer complex. The variation in the slow dissociation rate with cocaine
      concentration is well described with an equilibrium-binding model, where the
      dissociation rate approaches a saturation limit consistent with the dissociation
      equilibrium constant for cocaine-binding to the split aptamer. This single
      molecule methodology provides a sensitive readout of cocaine-binding based on the
      dissociation kinetics of the split aptamer, allowing one to distinguish target
      dependent aptamer assembly from background assembly. This methodology could be
      used to study other systems where target association affects the stability of
      aptamer duplexes.

PMID- 30280569
TI  - Fabrication of Air-Stable and Conductive Silk Fibroin Gels.
AB  - Owing to their promising applications in flexible electronics, researchers have
      extensively explored flexible and conductive gels. However, these gels have
      unsatisfactory strength and flexibility as well as easily dry in air. Herein, a
      rationally designed robust regenerated silk fibroin (RSF)-based gel with
      significant flexibility and strength, favorable conductivity, and excellent air
      stability is fabricated by inducing the conformation transition of RSF from
      random coil to beta-sheet in ionic liquid (IL)/water mixtures. We found that such
      RSF-based gels have a unique homogeneous network structure of RSF nanofibers,
      which is likely formed because of evenly distributed cross-links dominated by
      small-sized beta-sheet domains created during the conformation transition of RSF.
      Although the unique homogeneous nanostructure/network contributes toward
      improving the mechanical properties of these gels, it also provides pathways for
      ionic transport to help the gels preserve high conductivity of ILs. The prepared
      RSF-based gels display a remarkable air stability and reversible loss/absorption
      water capability in a wide humidity range environment primarily because of the
      distinguished combination of the IL and water. Therefore, the novel RSF-based
      gels hold a great potential in various applications as multifunctional, flexible,
      conductive materials, which are dispensed with encapsulation.

PMID- 30280570
TI  - Nanoid Canyons On-Demand: Electrically Switchable Surface Topography in Liquid
      Crystal Networks.
AB  - Topography is a key factor that governs important properties of surfaces, such as
      adhesion and wettability, and materials with switchable surface topographies will
      have switchable surface properties. We demonstrate a principle to generate
      electrically switchable surface topographies on the surface of a thin nematic
      liquid crystal elastomer film which is sandwiched between a continuous electrode
      and a random metal network. Voltage-controlled displacement of the metal network
      toward the continuous electrode is achieved, resulting in unprecedented
      topographical modulations in the range of 0-2.5 MUm. We show that this depth
      variation is significantly larger than the expected deformation because of
      electrostatic attraction between the network and the continuous electrode. This
      effect is explained by deformation due to the rotation of the liquid crystal side
      groups along the electric field lines.

PMID- 30280571
TI  - Stability and Transport of Spent Hen-Derived ACE-Inhibitory Peptides IWHHT, IWH,
      and IW in Human Intestinal Caco-2 Cell Monolayers.
AB  - Ile-Trp-His-His-Thr (IWHHT), initially identified as an ACE inhibitory peptide,
      was shown to have antioxidant and anti-inflammatory activities in cells and blood
      pressure lowering activity in animals. IWHHT was degraded into IWH and IW during
      simulated gastrointestinal digestion. The purpose of this study was to
      investigate the stability, permeability, and transport pathways of IWHHT, IWH,
      and IW across intestinal epithelium using human intestinal Caco-2 cell
      monolayers. IWHHT, IWH, and IW were partly degraded by aminopeptidase N or
      dipeptidyl peptidase IV, but they were transported intact, with apparent
      permeability coefficients of (22.0 +/- 1.42) * 10-8, (37.5 +/- 1.11) * 10-8, and
      (19.6 +/- 0.62) * 10-8 cm s-1, respectively. The results firstly evidenced an
      important role of aminopeptidase N in cleaving small ACE inhibitory peptides
      during transport. IWH was transported via both peptide transporter 1 (PepT1) and
      paracellular route, while IW was via PepT1 and IWHHT was via paracellular route
      only. Transport of IW implied that hydrophobic peptides (even with a small size),
      consisting of only highly hydrophobic amino acid residues, might not be
      transported via paracellular diffusion. This study suggested that all three
      peptides could pass through the intestinal epithelium and that the degraded IWH
      and IW might also contribute to the antihypertensive activity of IWHHT.

PMID- 30280572
TI  - Energy Harvesting in a Bodipy-Functionalized Rotaxane.
AB  - A rotaxane composed of two separate Bodipy-functionalized units can be
      synthesized with a high yield. The resulting structure shows a very efficient
      through-space energy transfer (FRET), acting as an energy funnel. Thus, maximum
      solar output in the visible region can be collected and converted into red light,
      which can be transformed efficiently with a fine-tuned photovoltaic device. The
      versatility of the synthetic pathway demonstrates the potential utility of
      rotaxane-based energy harvesting supramolecules assemblies.

PMID- 30280573
TI  - Lepadins I-K, 3- O-(3'-Methylthio)acryloyloxy-decahydroquinoline Esters from a
      Bahamian Ascidian Didemnum sp. Assignment of Absolute Stereostructures.
AB  - Three decahydroisoquinoline alkaloids, lepadins I-K, were isolated from a
      specimen of Didemnum sp. collected in the Bahamas. The structures of the new
      compounds were assigned by an integrated analysis of MS, IR, and 1H, 13C, and 2D
      NMR spectra. Like previously reported lepadins, the structures of the new
      compounds contain a decahydroquinoline heterocyclic core in lepadin I, and a new
      variation, an octahydroquinoline in lepadin J, but differ from earlier reported
      compounds by acylation of the 3-hydroxyl group by a rare 3'-methylthioacrylate.
      The absolute configuration of lepadin I was solved by interpretation of NOE
      measurements, and exciton coupled circular dichroism (ECCD) of the corresponding
      N- p-bromobenzoyl derivative. The latter constitutes a general method for
      determination of absolute configuration of the entire lepadin family. The
      configuration of the remote side-chain secondary carbinol was solved by the
      modified Mosher's esters method. Lepadin I inhibited butyrylcholineesterase
      (BuChE, IC50 3.1 MUM), but only weakly inhibited acetylcholineesterase (AChE)
      (10% at 100 MUM).

PMID- 30280575
TI  - Interpretation of Mass Spectral Data for the Cisplatin 1,2 Intrastrand Guanine
      Guanine Adduct.

PMID- 30280574
TI  - Absorption and Metabolism of Luteolin in Rats and Humans in Relation to in Vitro
      Anti-inflammatory Effects.
AB  - Luteolin is a flavonoid present in plants in the form of aglycone or glucosides.
      In this study, luteolin glucosides (i.e., luteolin-7- O-beta-d-glucoside,
      luteolin-7- O-[2-(beta-d-apiosyl)-beta-d-glucoside], and luteolin-7- O-[2-(beta-d
      apiosyl)-6-malonyl-beta-d-glucoside]) prepared from green pepper leaves as well
      as luteolin aglycone were orally administered to rats. Regardless of the
      administered luteolin form, luteolin glucuronides were mainly detected from
      plasma and organs. Subsequently, luteolin aglycone, the most absorbed form of
      luteolin in rats, was orally administered to humans. As a result, luteolin-3'- O
      sulfate was mainly identified from plasma, suggesting that not only luteolin form
      but also animal species affect the absorption and metabolism of luteolin. When
      LPS-treated RAW264.7 cells were treated with luteolin glucuronides and luteolin
      sulfate (the characteristic metabolites identified from rats and humans,
      respectively), the different luteolin conjugates were metabolized in different
      ways, suggesting that such difference in metabolism results in their difference
      in anti-inflammatory effects.

PMID- 30280577
TI  - Chromosome 17 Missing Proteins: Recent Progress and Future Directions as Part of
      the neXt-MP50 Challenge.
AB  - The Chromosome-centric Human Proteome Project (C-HPP), announced in September
      2016, is an initiative to accelerate progress on the detection and
      characterization of neXtProt PE2,3,4 "missing proteins" (MPs) with a mandate to
      each chromosome team to find about 50 MPs over 2 years. Here we report major
      progress toward the neXt-MP50 challenge with 43 newly validated Chr 17 PE1
      proteins, of which 25 were based on mass spectrometry, 12 on protein-protein
      interactions, 3 on a combination of MS and PPI, and 3 with other types of data.
      Notable among these new PE1 proteins were five keratin-associated proteins, a
      single olfactory receptor, and five additional membrane-embedded proteins. We
      evaluate the prospects of finding the remaining 105 MPs coded for on Chr 17,
      focusing on mass spectrometry and protein-protein interaction approaches. We
      present a list of 35 prioritized MPs with specific approaches that may be used in
      further MS and PPI experimental studies. Additionally, we demonstrate how in
      silico studies can be used to capture individual peptides from major data
      repositories, documenting one MP that appears to be a strong candidate for PE1.
      We are close to our goal of finding 50 MPs for Chr 17.

PMID- 30280576
TI  - Multiproteases Combined with High-pH Reverse-Phase Separation Strategy Verified
      Fourteen Missing Proteins in Human Testis Tissue.
AB  - Subsequent to conducting the Chromosome-Centric Human Proteome Project, we have
      focused on human testis-enriched missing proteins (MPs) since 2015. For protein
      coverage to be enhanced, a multiprotease strategy was used for separation of
      samples by 10% SDS-PAGE. For the separating efficiency to be improved, a high-pH
      reverse phase (RP) separation strategy was applied to fractionate complex samples
      in this study. A total of 11,558 proteins was identified, which is the largest
      proteome data set for single human tissue sample so far. On the basis of this
      large-scale data set, we verified 14 MPs (PE2) in neXtProt (2018-01) after
      spectrum quality analysis, isobaric post-translational modification, and single
      amino acid variant filtering, and synthesized peptide matching. Tissue expression
      analysis showed that 3 of 14 MPs were testis-specific proteins. Functional
      analysis showed that 10 of 14 MPs were closely related to liver tumor, liver
      carcinoma, and hepatocellular carcinoma. Another 100 MPs were listed as
      candidates but required additional verification information. All MS data sets
      have been deposited into the ProteomeXchange with the identifier PXD009737.

PMID- 30280578
TI  - Clozapine-Associated Cytomegalovirus Colitis and Related Critical Illness in a
      Patient With Neither Neutropenia Nor Agranulocytosis.

PMID- 30280579
TI  - Exposure to community violence and substance use among Black men who have sex
      with men: examining the role of psychological distress and criminal justice
      involvement.
AB  - Young Black MSM (YBMSM) are disproportionately affected by violence, criminal
      justice involvement, and other structural factors that also increase
      vulnerability to HIV. This study examined associations between exposure to
      community violence (ECV) and substance use, psychological distress, and criminal
      justice involvement (CJI) among YBMSM in Chicago, IL. Respondent driven sampling
      was used to recruit a sample of 618 YBMSM (aged 16-29) from the South Side of
      Chicago between June 2013 and July 2014. Weighted logistic regression assessed
      the direct effects of ECV, CJI, and psychological distress on substance use
      outcomes. Indirect effects were assessed via path analysis with mean and variance
      adjusted weighted least squares estimation and sampling weights. Over 90%
      reported lifetime exposure to violence, 41% had history of CJI, and substance use
      was common. Almost one-third reported daily or more frequent marijuana use; 17%
      reported substance use related problems and drug use other than marijuana. ECV
      was directly and positively associated with CJI, psychological distress, and
      problematic substance use, with significant indirect effects from ECV to?
      problematic substance use via CJI and psychological distress. HIV prevention
      interventions for YBMSM should address the underlying contextual drivers of
      substance use and psychological distress, including violence exposure and
      criminal justice involvement.

PMID- 30280581
TI  - Previously Banned Magnets as Foreign Bodies in the Lower Urinary System: A Single
      Institution Case Series and Review of the Literature.

PMID- 30280580
TI  - A Brief Provider Training Video Improves Comfort With Recommending the Human
      Papillomavirus Vaccine.
AB  - The American Academy of Pediatrics California Chapter 3 created a 20-minute
      training video targeting barriers to strong provider recommendation of the human
      papillomavirus (HPV) vaccine. The video included clinical vignettes featuring
      pediatricians modeling counseling techniques with vaccine-hesitant families.
      Ninety-six multidisciplinary providers (including pediatric residents) at 6 sites
      viewed the video and completed baseline and posttest questionnaires assessing
      their vaccine knowledge, attitudes toward vaccination, and comfort with skills
      needed to facilitate vaccination. Following the intervention, providers had
      substantial and statistically significant ( P < .05) improvements in multiple
      areas assessed, particularly knowledge of the burden of HPV-related disease in
      males and changes in vaccine response with age; likelihood of "strongly agreeing"
      that vaccination should not be delayed beyond preadolescence and that HPV vaccine
      is safe; and feeling "very comfortable" counseling vaccine-hesitant parents and
      facilitating vaccine completion. This cost-effective and easily disseminated
      training modality shows promise in increasing provider comfort with HPV vaccine
      counseling.

PMID- 30280582
TI  - Understanding preferences regarding consent for pragmatic trials in acute care.
AB  - BACKGROUND: There has been debate about the role of consent in pragmatic trials
      comparing qualitatively similar interventions. Consent preferences may differ in
      acute care contexts, given severe illness, time constraints, and other barriers
      to consent. In addition, studies have not assessed the impact of disclosing
      financial considerations as a justification for trials. This study was designed
      to assess preferences of the general public regarding consent for a pragmatic
      trial in ST-elevation myocardial infarction. METHODS: This survey was completed
      using an online, probability-based panel representative of the US population. It
      incorporated a randomized, experimental (2 * 2) design assessing (1) preference
      for written consent versus an alternative (notification after enrollment or brief
      verbal consent) and (2) impact of including cost as a motivating factor for the
      trial. The survey used a scenario based on a recent pragmatic trial in ST
      elevation myocardial infarction. Primary independent variables were personal
      preference and recommendation as a member of a review board regarding written
      consent versus the assigned alternative strategy and personal attitude toward
      trial enrollment. Descriptive analyses were conducted using post-stratification
      weights. Regression models were created to examine relationships between
      demographic variables and consent preference and willingness to enroll. Provision
      of cost information was incorporated into a regression model to examine its
      impact on consent preference. RESULTS: The study included 2027 participants. Of
      those participants, 51.1% versus 45.8% stated a personal preference for written
      consent versus notification after enrollment; however, 60.0% versus 35.5%
      preferred brief verbal consent to written consent. Even among respondents stating
      they would be unlikely to enroll in the trial if asked, more respondents (50.6%)
      preferred brief verbal consent. The preference for verbal consent was generally
      shared across demographic categories, although lower educational attainment was
      associated with reduced acceptance (p = 0.001 for trend). Respondents were more
      likely to support an alternative to written consent when asked their personal
      preference than when asked their recommendation as a member of a review board.
      The provision of cost information did not have a meaningful effect on consent
      preferences, attitudes toward enrollment, or views about the study. CONCLUSION:
      Respondents generally supported prospective involvement in enrollment decisions
      in the setting of acute myocardial infarction and were particularly supportive of
      brief verbal consent. This support persisted across demographic categories. The
      finding that individuals were more likely to support alternatives to written
      consent when asked for a personal preference rather than as a "committee member"
      suggests that conservative institutional approaches to consent could hinder
      implementation of more patient-centered approaches. The role of cost transparency
      in consent discussions warrants further study.

PMID- 30280583
TI  - Variability and Influencing Factors of QOL in Breast Cancer Patients Having
      Chemotherapy.
AB  - Variability and factors influencing quality of life (QOL) in breast cancer
      patients having chemotherapy were examined in a longitudinal prospective cohort
      study in two teaching hospitals in China. Physical, mental, social/family, and
      functional QOL changed significantly over time with varying patterns. In
      addition, various factors influenced the QOL of breast cancer patients at each
      chemotherapy cycle. Health professionals should focus on critical time periods
      during chemotherapy, particularly at baseline and during the fourth and fifth
      cycles when the QOL in our sample was at the lowest point, and they should
      provide additional support to patients to ensure that chemotherapy is delivered
      in an optimal fashion.

PMID- 30280584
TI  - Peripheral Eosinophilia Found in Pediatric Enterobius vermicularis Infections.
AB  - Enterobius vermicularis, the common pinworm, is well known in North America as a
      parasitic infection, mainly affecting children. It is a very contagious organism,
      and it is responsible for a high number of infections in the United States each
      year. A rise in eosinophilia is linked to most parasitic infections. However, the
      correlation between eosinophilia and enterobiasis infections is not well
      documented in the literature. In this article, we present 3 cases involving
      patients seen for pediatric gastroenterology consultation with concern for
      inflammatory bowel disease. As part of their evaluation, each patient was found
      to have eosinophilia of unknown significance with an ultimate diagnosis of
      pinworm infections made by endoscopy. Their illness presentation did not include
      classic enterobiasis symptoms such as rectal pruritus or nighttime irritability.
      These cases support a link between eosinophilia and enterobiasis that may be
      instructive for pediatric providers seeing patients with eosinophilia for which
      there is no readily apparent underlying cause.

PMID- 30280585
TI  - Faculty Attitudes Toward Rhinology Fellowship Training: A Survey of Rhinology
      Fellowship Programs.
AB  - Background The number of rhinology fellowship programs has grown rapidly over the
      past decade. To date, no standardization or accreditation process exists, raising
      the potential for disparate programs. The attitudes of faculty regarding training
      are important to elucidate the educational experience of rhinology fellowship.
      Methods An anonymous, web-based survey of rhinology faculty assessed the
      subjective attitudes toward various domains of fellowship training including
      surgery, office-based procedures, research, and career development. A 5-point
      Likert-type scale assessing importance was used (1-not at all important, 5
      extremely important). Results A total of 34 faculty (response rate 35.8%)
      completed the survey. The surgical procedures that received the highest mean
      importance scores were endoscopic surgery for advanced inflammatory disease
      (median = 5), cerebrospinal fluid leak closure (5), and extended endoscopic sinus
      surgery (5). The procedures with the lowest scores were nasal valve repair (2),
      inferior turbinate surgery (3), and open approaches to the sinuses (4). A wide
      range of responses was noted for the minimum target number of fellow cases for
      the surveyed procedures. Higher importance scores were noted for direct attending
      supervision (5) when compared to fellow autonomy (4, P < .001) or shadowing (3.5,
      P < .001) in the operating room. Higher scores were noted for career preparation
      in academic (4) versus private practice (3, P < .001) and providing opportunities
      for clinical (4) versus basic science research (2, P < .001). The majority of
      faculty felt that there were too many fellowship positions with respect to the
      market place for private practice (58.8%), academic jobs (85.3%), and overall
      societal need (61.8%). Conclusion A range of faculty attitudes with respect to
      fellowship training was noted in this study. Continued assessment and refinement
      of the educational experience in rhinology fellowships is necessary.

PMID- 30280587
TI  - Co-occurrence of acute ophthalmoplegia (without ataxia) and idiopathic
      intracranial hypertension.
AB  - BACKGROUND: Acute ophthalmoparesis without ataxia was designated as 'atypical
      Miller Fisher syndrome' as it presents with progressive, relatively symmetrical
      ophthalmoplegia, but without ataxia nor limb weakness, in the presence of anti
      GQ1b antibody. Idiopathic intracranial hypertension is characterized by signs of
      raised intracranial pressure occurring in the absence of cerebral pathology, with
      normal composition of cerebrospinal fluid and a raised opening pressure of more
      than 20 cmH2O during lumbar puncture. We aim to report a rare case of acute
      ophthalmoplegia with co-occurrence of raised intracranial pressure. CASE
      DESCRIPTION: A 28-year-old gentleman with body mass index of 34.3 was referred to
      us for management of double vision of 2 weeks duration. His symptom started after
      a brief episode of upper respiratory tract infection. His best corrected visual
      acuity was 6/6 OU. He had bilateral sixth nerve palsy worse on the left eye and
      bilateral hypometric saccade. His deep tendon reflexes were found to be
      hyporeflexic in all four limbs. No sensory or motor power deficit was detected,
      and his gait was normal. Plantar reflexes were downwards bilaterally and
      cerebellar examination was normal. Both optic discs developed hyperaemia and
      swelling. Magnetic resonance imaging of brain was normal and lumbar puncture
      revealed an opening pressure of 50 cmH2O. Anti-GQ1b IgG and anti-GT1a IgG
      antibody were tested positive. CONCLUSION: Acute ophthalmoparesis without ataxia
      can present with co-occurrence of raised intracranial pressure. It is important
      to have a full fundoscopic assessment to look for papilloedema in patients
      presenting with Miller Fisher syndrome or acute ophthalmoparesis without ataxia.

PMID- 30280586
TI  - Two-Year Follow-Up and Remodeling Kinetics of ChonDux Hydrogel for Full-Thickness
      Cartilage Defect Repair in the Knee.
AB  - Objective To determine performance and repair kinetics of the ChonDux hydrogel
      scaffold for treating focal articular cartilage defects in the knee over 24
      months. Design This assessor-blinded trial evaluates ChonDux hydrogel scaffold
      implantation in combination with microfracture in 18 patients across 6 sites.
      Male and female patients 18 to 65 years of age with full-thickness femoral
      condyle defects 2 to 4 cm2 in area were enrolled. Eligible patients received
      ChonDux treatment followed by rehabilitation. Defect volume fill was evaluated
      after 3, 6 (primary outcome), 12, 18, and 24 months by assessor blinded magnetic
      resonance imaging (MRI) analysis. Secondary outcomes were T2-weighted MRI
      relaxation time and patient surveys via visual analogue scale (VAS) pain and
      International Knee Documentation Committee (IKDC) knee function scoring. Results
      ChonDux maintained durable tissue restoration over 24 months with final defect
      percent fill of 94.2% +/- 16.3% and no significant loss of fill volume at any
      time points. Tissues treated with ChonDux maintained T2 relaxation times similar
      to uninjured cartilage between 12 and 24 months. VAS pain scoring decreased
      between 1 and 6 weeks, and IKDC knee function scores improved by approximately
      30.1 with ChonDux over 24 months. Conclusion ChonDux treatment is a safe adjunct
      to microfracture therapy and promotes stable restoration of full thickness
      articular cartilage defects for at least 24 months.

PMID- 30280588
TI  - An in vivo confocal microscopy study of corneal changes in pseudoexfoliation
      syndrome.
AB  - PURPOSE: To evaluate, through the in vivo confocal microscopy, the pathological
      changes of each corneal layer in eyes affected by pseudoexfoliation syndrome.
      METHODS: We studied 40 eyes of 40 patients with diagnosis of unilateral senile
      cataract associated with pseudoexfoliation syndrome and 40 eyes of 40 control
      subjects with senile cataract without pseudoexfoliation syndrome. All patients
      underwent a complete ophthalmic examination including best corrected visual
      acuity, slit-lamp examination, corneal sensitivity measurement using a Cochet
      Bonnet nylon thread esthesiometer, and anterior segment optical coherence
      tomography (Visante OCT, Carl Zeiss Meditec AG, Germany); in vivo confocal
      microscopy of corneal sections (endothelium, stroma, sub-basal nerve plexus, and
      superficial and basal epithelium) was performed with the ConfoScan 4.0 (Nidek,
      Japan). RESULTS: In pseudoexfoliation syndrome group, the mean corneal
      sensitivity was 44.1 +/- 1.3 mm and in the control group was 55.6 +/- 4.7 mm. The
      corneas of the eyes with pseudoexfoliation syndrome were significantly less
      sensitive than those of control group eyes (p < 0.001). Pseudoexfoliation
      syndrome eyes had a lower nerve density and less nerve beadings and a higher
      degree of tortuosity in sub-basal plexus compared to the control group. The cell
      density of epithelial and endothelial layers was significantly lower in
      pseudoexfoliation syndrome eyes than controls. In 80% of pseudoexfoliation
      syndrome eyes, we found activated keratocytes and inflammatory cells in the
      anterior stroma. CONCLUSION: Our study demonstrates the morpho-structural corneal
      alterations in eyes affected by pseudoexfoliation syndrome, using corneal in vivo
      confocal microscopy as a non-invasive and high-reproducible technique to evaluate
      pathophysiology of each corneal layer; the sub-basal nerve plexus alterations are
      correlated with the lower corneal sensitivity.

PMID- 30280590
TI  - Bilateral noncalcified astrocytic hamartomas in retinitis pigmentosa: Multimodal
      imaging evaluation over 8 years of follow-up.
AB  - PURPOSE: To report the evolution of optic disk noncalcified astrocytic hamartomas
      in a patient with retinitis pigmentosa throughout 8 years of follow-up. METHODS:
      Case report. RESULTS: A 42-year-old white man with a diagnosis of retinitis
      pigmentosa was referred to our medical retinal center for the first time in 2010,
      for the development of a new optic nerve head lesion in the right eye. Fundus
      examination, fundus autofluorescence, fluorescein and green indocyanine
      angiography, spectral-domain optical coherence tomography were performed and
      confirmed the presence of a papillary noncalcified astrocytic hamartoma in the
      right eye. Four years later, multimodal imaging evaluation revealed in the left
      eye the presence of a first optic disk benign tumor, and in 2018, a second in the
      nasal retina, while in the right eye the sole papillary lesion increased slightly
      in size. CONCLUSIONS: Noncalcified astrocytic hamartomas can occur in patients
      with retinitis pigmentosa and can increase in size and number in time. A complete
      multimodal imaging evaluation is necessary to identify and classify any kind of
      new lesion that, as known, are associated with these group of hereditary retinal
      degenerations.

PMID- 30280589
TI  - Molecular modelling studies on cinnoline-based BTK inhibitors using docking and
      structure-based 3D-QSAR.
AB  - BTK inhibitors have been proved as an effective target for B-cell malignancies.
      Ibrutinib is the most advanced irreversible BTK inhibitor for treating mantle
      cell lymphoma/chronic lymphocytic leukaemia but with existing drug resistance and
      adverse effects. To design novel effective and safety reversible BTK inhibitors,
      115 newly cinnoline analogues were selected to perform molecular docking and 3D
      QSAR study because of the main scaffold similarity to Ibrutinib. Both established
      CoMFA and CoMSIA models obtained high predictive and satisfactory value.
      CoMFA/CoMSIA contour maps demonstrated that bulky substitutions are preferred at
      R1 and R3 positions, and introducing hydrophilic and negative electrostatic
      substitutions at R1 positions is important for improving BTK inhibitory
      activities. These results will be useful to provide clues for rationally
      designing novel and high potency BTK inhibitors.

PMID- 30280591
TI  - Amplitude Instability of Somatosensory Evoked Potentials as an Indicator of
      Delayed Cerebral Ischemia in a Case of Subarachnoid Hemorrhage.
AB  - We describe a 55-year-old male patient with a subarachnoid hemorrhage (SAH) as a
      result of left middle cerebral artery (MCA) aneurysm rupture, who underwent
      continuous electroencephalogram (EEG) and somatosensory evoked potential (cEEG
      SEP) monitoring that showed an unusual SEP trend pattern. EEG was continuously
      recorded, and SEPs following stimulation of median nerves were recorded every 50
      minutes, with the amplitude and latency of the cortical components automatically
      trended. An increase in intracranial pressure required a left decompressive
      craniectomy. cEEG-SEP monitoring was started on day 7, which showed a prolonged
      (24 hours) instability of SEPs in the left hemisphere. During this phase, left
      MCA vasospasm was demonstrated by transcranial Doppler (TCD), and computed
      tomography perfusion (CTP) showed a temporo-parieto-occipital ischemic penumbra.
      Following intravascular treatment, hypoperfusion and the amplitude of cortical
      SEPs improved. In our case, a prolonged phase of SEP amplitude instability during
      vasospasm in SAH correlated with a phase of ischemic penumbra, as demonstrated by
      CTP. In SAH, SEP instability during continuous monitoring is a pattern of alert
      that can allow treatments capable of avoiding irreversible neurological
      deterioration.

PMID- 30280592
TI  - Nitrogen isotope fractionation factors (alpha) measured and estimated from the
      volatilisation of ammonia from water at pH 9.2 and pH 8.5.
AB  - This paper examines the nitrogen isotope fractionation factors (alpha) associated
      with the volatilisation of ammonia from water under controlled conditions at two
      pH values (8.5 and 9.2). This experiment assumed the continuous removal of
      ammonia at a single purge rate of 10 mL air min-1. The fractionation resulting
      from the removal of total ammonia from the water into an acid trap was named the
      observed isotope fractionation factor (alphaobs), and it was measured as 1.019
      (+/-0.0025) at pH 8.5 and 1.030 (+/-0.0025) at pH 9.2. The observed isotope
      fractionation factor includes the equilibrium isotope fractionation factor
      (alphaeq) and the kinetic isotope fractionation factor (alphakin), each one
      mathematically derived from the experimental data. The equilibrium and kinetic
      isotope fractionation factors were estimated as alphaeq = 1.036 (+/-0.0014) and
      alphakin = 1.050 (+/-0.003), respectively. Our results are compared to other
      previously measured and estimated fractionation factors.

PMID- 30280593
TI  - One-Stage Metatarsal Interposition Lengthening With an Autologous Fibula Graft
      for Treatment of Brachymetatarsia.
AB  - OBJECTIVE: Brachymetatarsia is defined as the pathological shortening of a
      metatarsal bone, which can cause cosmetic problems and pain in the forefoot. The
      main surgical treatment options are: extension osteotomy, interposition of a bone
      graft, and callus distraction. Usually, a bone graft from the iliac crest is used
      for the interposition osteotomy. The operative technique of graft extraction from
      the fibula has not been described in the literature yet. METHODS: Eight feet with
      brachymetatarsia in 5 patients were evaluated retrospectively. The minimum follow
      up period was 2 years. Via a dorsal V/Y skin incision, a central osteotomy on the
      metatarsal bone was done. A graft was obtained from the anterior fibula. The
      graft was inserted and fixed by a locking plate. Additional soft tissue
      procedures were done. RESULTS: We had bony consolidation in all cases. The mean
      extension was 9.01 mm (5.49 to 12.54 mm). This corresponded to a mean 20.3%
      extension of the entire metatarsal. High patient satisfaction as well as high
      satisfaction regarding the cosmetic results were achieved. There were no
      postoperative complications. The range of motion of the metatarsal-phalangeal
      joint IV was 20% less preoperative in terms of plantar flexion. Standing up on
      tiptoes was possible in all patients postoperatively. One patient reported mild
      symptoms after sports activities. CONCLUSIONS: Because of its anatomy the graft
      adapts to the metatarsal IV bone. As our study showed, harvesting from the distal
      fibula causes no functional restriction. In terms of wound and bone healing as
      well as pain symptoms, this method should be considered as an alternative to the
      standard iliac graft.

PMID- 30280594
TI  - The efficacy of "IOL-Vip Revolution" telescopic intraocular lens in age-related
      macular degeneration cases with senile cataract.
AB  - PURPOSE: To evaluate the efficacy of the IOL-Vip Revolution telescopic
      intraocular lens in age-related macular degeneration patients. METHODS: A total
      of 13 eyes of 12 age-related macular degeneration patients with senile cataract
      were enrolled. Selection of the patients was done by means of a low vision
      diagnostic and rehabilitative program (IOL-Vip software) that evaluates residual
      visual function. After standard phacoemulsification surgery, the incision site
      was enlarged and the IOL-Vip Revolution system was implanted in the capsular bag.
      The outcome measures were best corrected visual acuity, contrast sensitivity,
      anterior chamber depth, endothelial cell density, central corneal thickness, and
      quality-of-life questionnaire. RESULTS: The mean age of the subjects was 72.3 +/-
      8.5 years. The mean positive power of the intraocular lens was 59 +/- 2 D and the
      negative intraocular lens power was standard (-46 D). Pre- and postoperative best
      corrected visual acuity were 1.08 +/- 0.14 and 0.81 +/- 0.16 logMAR in the
      operated eye and 1.13 +/- 0.36 and 1.01 +/- 0.40 logMAR in the unoperated eye,
      respectively. The best corrected visual acuity was increased significantly in
      both operated and unoperated eyes (p = 0.005 and 0.021, respectively). Quality of
      life and anterior chamber depth increased significantly (p = 0.018 and 0.008,
      respectively), while endothelial cell density decreased (p = 0.002). No
      significant differences were detected in central corneal thickness or contrast
      sensitivity (p = 0.133 and 0.684, respectively). CONCLUSION: The results showed
      that IOL-Vip Revolution telescopic intraocular lens is a promising treatment
      option in age-related macular degeneration patients. The rehabilitation program
      may have an important role in the restored clinical results, which also provided
      visual improvement in the unoperated eyes.

PMID- 30280595
TI  - Altered Functional Connectivity of Alpha Rhythm in Obsessive-Compulsive Disorder
      During Rest.
AB  - Obsessive-compulsive disorder (OCD) is a common inheritable psychiatric disorder
      characteristic of repetitive thinking, imagination (obsession), and stereotyped
      behaviors (compulsive). To explore whether there is an alteration of brain
      functional connectivity (BFC) in patients with OCD during rest,
      electroencephalogram (EEG) data of healthy controls (HCs) and patients with OCD
      were collected during rest in both eyes-closed and eyes-open states.
      Synchronization likelihood and graph theory were applied to construct and analyze
      brain functional networks of patients with OCD and HCs. Patients with OCD showed
      abnormal graph-theoretic parameters and impaired small world features in the
      alpha and beta bands. In addition, the topological analysis consistently showed
      that the long-range BFC of alpha rhythm was significantly reduced in the
      bilateral posterior areas in patients with OCD in comparison with HCs, while the
      BFC in the beta rhythm was significantly increased only in the eyes-open state.
      The findings suggest that the BFC of patients with OCD show abnormal small-world
      features and altered topological structure during rest, mainly in alpha and beta
      bands, which may provide a new insight for the diagnosis and treatment of OCD.

PMID- 30280597
TI  - Periarterial fat from two human vascular beds is not a source of aldosterone to
      promote vasoconstriction.
AB  - Mouse adipocytes have been reported to release aldosterone and reduce endothelium
      dependent relaxation. It is unknown if perivascular adipose tissue (PVAT)
      releases aldosterone in humans. The present experiments were designed to test the
      hypothesis that human PVAT releases aldosterone and induces endothelial
      dysfunction. Vascular reactivity was assessed in human internal mammary and renal
      segmental arteries obtained at surgery. The arteries were prepared with/without
      PVAT and changes in isometric tension were measured in response to the
      vasoconstrictor thromboxane prostanoid (TP) receptor agonist U46619 and the
      endothelium-dependent vasodilator acetylcholine. The effects of exogenous
      aldosterone and of MR antagonist eplerenone were determined. Aldosterone
      concentrations were measured by ELISA in conditioned media incubated with human
      adipose tissue with/without angiotensin II stimulation. Presence of aldosterone
      synthase and MR mRNA was examined in perirenal, abdominal and mammary PVAT by
      PCR. U46619-induced tension and acetylcholine-induced relaxation were unaffected
      by exogenous and endogenous aldosterone (addition of aldosterone and MR blocker)
      in mammary and renal segmental arteries, both in the presence and absence of
      PVAT. Aldosterone release from incubated perivascular fat was not detectable.
      Aldosterone synthase expression was not consistently observed in human adipose
      tissues in contrast to that of MR. Thus, exogenous aldosterone does not affect
      vascular reactivity and endothelial function in ex vivo human arterial segments
      and the tested human adipose tissues have no capacity to synthesize/release
      aldosterone. In perspective, physiologically relevant effects of aldosterone on
      vascular function in humans are caused by systemic aldosterone originating from
      the adrenal gland.

PMID- 30280596
TI  - Umbilical Cord Nonseverance and Adverse Neonatal Outcomes.

PMID- 30280598
TI  - Dicer deficiency in proximal tubules exacerbates renal injury and
      tubulointerstitial fibrosis and upregulates Smad2/3.
AB  - Renal fibrosis is a common pathological feature in chronic kidney disease (CKD),
      including diabetic kidney disease (DKD) and obstructive nephropathy. Multiple
      microRNAs have been implicated in the pathogenesis of both DKD and obstructive
      nephropathy although the overall role of microRNAs in tubular injury and renal
      fibrosis in CKD is unclear. Dicer (a key RNase III enzyme for microRNA
      biogenesis) was specifically ablated from kidney proximal tubules in mice via the
      Cre/lox system to deplete micoRNAs. Proximal tubular Dicer knockout (PT- Dicer
      KO) mice and wild-type (WT) littermates were subjected to streptozotocin (STZ)
      treatment to induce DKD or unilateral ureteral obstruction (UUO) to induce
      obstructive nephropathy. Renal hypertrophy, renal tubular apoptosis, kidney
      inflammation, and tubulointerstitial fibrosis were examined. Comparing to WT
      mice, PT- Dicer KO mice showed more severe tubular injury and renal inflammation
      following STZ treatment. These mice also developed higher levels of
      tubolointerstitial fibrosis. Meanwhile, PT- Dicer KO mice had a significantly
      higher Smad2/3 expression in kidneys than WT mice (6 months of age) in both
      control and STZ treated mice. Similarly, UUO induced more severe renal injury,
      inflammation, and interstitial fibrosis in PT- Dicer KO mice than WT. Although we
      did not detect obvious Smad2/3 expression in sham-operated mice (2-3 months old),
      significantly more Smad2/3 was induced in obstructed PT- Dicer KO kidneys. These
      results supported a protective role of microRNA synthesis in renal injury and
      fibrosis development in CKD, specifically in DKD and obstructive nephropathy.
      Depletion of Dicer and microRNAs may up-regulate Smad2/3 related signaling
      pathway to enhance the progression of CKD.

PMID- 30280599
TI  - Skeletal muscle fibrosis is associated with decreased muscle inflammation and
      weakness in patients with chronic kidney disease.
AB  - Muscle dysfunction is an important cause of morbidity among patients with chronic
      kidney disease (CKD). Although muscle fibrosis is present in a CKD rodent model,
      its existence in humans and its impact on physical function are currently
      unknown. We examined isometric leg extension strength and measures of skeletal
      muscle fibrosis and inflammation in vastus lateralis muscle from CKD patients
      (n=10) and healthy, sedentary controls (n=10). Histochemistry and
      immunohistochemistry were used to assess muscle collagen and macrophage and
      fibro/adipogenic progenitor (FAP) cell populations, and RT-qPCR was used to
      assess muscle-specific inflammatory marker expression. Muscle collagen content
      was significantly greater in CKD compared with control (18.8 +/- 2.1% vs. 11.7 +/
      0.7% collagen area, p=0.008), as was staining for collagen I, pro-collagen I,
      and a novel collagen-hybridizing peptide that binds remodeling collagen. Muscle
      collagen was inversely associated with leg extension strength in CKD (r= -0.74,
      p=0.01). FAP abundance was increased in CKD, was highly correlated with muscle
      collagen (r=0.84, p<0.001), and was inversely associated with TNF-alpha
      expression (r= -0.65, p=0.003). TNF-alpha, CD68, CCL2, and CCL5 mRNA were
      significantly lower in CKD than control, despite higher serum TNF-alpha and IL-6.
      Immunohistochemistry confirmed fewer CD68+ and CD11b+ macrophages in CKD muscle.
      In conclusion, skeletal muscle collagen content is increased in humans with CKD
      and is associated with functional parameters. Muscle fibrosis correlated with
      increased FAP abundance, which may be due to insufficient macrophage-mediated TNF
      alpha secretion. These data provide a foundation for future research elucidating
      the mechanisms responsible for this newly identified human muscle pathology.

PMID- 30280600
TI  - Arginine reprogramming in ADPKD results in arginine-dependent cystogenesis.
AB  - Research into metabolic reprogramming in cancer has become commonplace, yet this
      area of research has only recently come of age in nephrology. In light of the
      parallels between cancer and ADPKD, the latter is currently being studied as a
      metabolic disease. In clear cell renal cell carcinoma (RCC), which is now
      considered a metabolic disease, we and others have shown derangements in the
      enzyme arginosuccinate synthase (ASS1) resulting in RCC cells becoming
      auxotrophic for arginine and leading to a new therapeutic paradigm involving
      reducing extracellular arginine. Based on our earlier finding that glutamine
      pathways are reprogrammed in ARPKD, and given the connection between arginine and
      glutamine synthetic pathways via citrulline, we investigated the possibility of
      arginine reprogramming in ADPKD. We now show that, in a remarkable parallel to
      RCC, ASS1 expression is reduced in murine and human ADPKD, and arginine depletion
      results in a dose dependent compensatory increase in ASS1 levels as well as
      decreased cystogenesis in vitro and ex vivo with minimal toxicity to normal
      cells. Non-targeted metabolomics analysis of mouse kidney cell lines grown in
      arginine-deficient vs. arginine-replete media suggests arginine-dependent
      alterations in the glutamine and proline pathways. Thus, depletion of this
      conditionally-essential amino acid by dietary or pharmacological means, such as
      with arginine-degrading enzymes, may be a novel treatment for this disease.

PMID- 30280602
TI  - Beyond the microscope: interpreting renal biopsy findings in the era of precision
      medicine.
AB  - As rapid progress in science and biotechnology is affecting the practice of renal
      medicine, increasingly precise diagnostic assessment is needed to select the most
      effective therapeutic approach for individual patients. The kidney biopsy remains
      the gold standard for the diagnosis of renal disease, but the field of renal
      pathology is evolving, classification of renal parenchyma lesions and
      histopathological diagnostic criteria are undergoing more validation and updates,
      and new technologies and assays are sought to improve efficiency and accuracy of
      the diagnostic process. How new knowledge and scientific advances may potentially
      affect renal pathology is discussed.

PMID- 30280601
TI  - Anti-C5a complementary peptide mitigates zymosan-induced severe peritonitis with
      fibrotic encapsulation in rat pretreated with methylglyoxal.
AB  - In a previous study of fungal peritoneal injury in peritoneal dialysis (PD)
      patients, complement (C)-dependent pathological changes were developed in zymosan
      (Zy)-induced peritonitis by peritoneal scraping. However, the injuries were
      limited to the parietal peritoneum and did not show any fibrous encapsulation of
      the visceral peritoneum, which differs from human encapsular peritoneal sclerosis
      (EPS). We investigated peritoneal injury in a rat model of Zy-induced peritonitis
      pretreated with methylglyoxal instead of scraping (Zy/MGO peritonitis) to clarify
      the role of C in the process of fibrous encapsulation of the visceral peritoneum.
      Therapeutic effects of an anti-C5a complementary peptide, AcPepA, on peritonitis
      were also studied. In Zy/MGO peritonitis, peritoneal thickness, fibrin exudation,
      accumulation of inflammatory cells, and deposition of C3b and C5b-9 with loss of
      membrane C regulators were increased along the peritoneum until day 5. On day 14,
      fibrous encapsulation of the visceral peritoneum was observed, resembling human
      EPS. Peritoneal injuries and fibrous changes were significantly improved with
      AcPepA treatment, even when AcPepA was administered following injection of Zy in
      Zy/MGO peritonitis. The data show that C5a might play a role in the development
      of encapsulation-like changes in the visceral peritoneum in Zy/MGO peritonitis.
      AcPepA might have therapeutic effects in fungal infection-induced peritoneal
      injury by preventing subsequent development of peritoneal encapsulation.

PMID- 30280603
TI  - Variations of perceived load and well-being between normal and congested weeks in
      elite case study handball team.
AB  - The aim of this study was two-fold: (i) to analyze the variations in internal
      load and well-being in professional handball players between normal and congested
      weeks and (ii) to analyze the variations between training days within weeks.
      Twenty male players (26.5 +/- 4.9 yo) were monitored during a full season. MD-1
      (match day -1) revealed larger decreases in muscle soreness (-17.3%, [-26.6;
      6.9]) and fatigue (-16.6%, [-24.8;-7.4]) in congested weeks. Regarding MD-2,
      larger decreases in DOMS (-19.9%, [-30.5;-7.6]), fatigue (-19.7%, [-30.0;-7.9]
      and the Hooper index (-16.7%, [-25.6;-6.7]) were found in congested weeks. The
      results of this study reveal that larger variations between normal and congested
      weeks occurred in MD-2 and MD-3, with greater values of load and lower levels of
      well-being occurring in normal weeks. Within-weeks changes revealed greater loads
      occurring on MD-3 and MD-2 in comparison to MD-1; in the opposite way, greater
      values of muscle soreness and fatigue occurred on MD-1.

PMID- 30280604
TI  - Prospective evaluation of anesthetic protocols during pediatric ophthalmic
      surgery.
AB  - PURPOSE: To date, no protocol of anesthesia for pediatric ophthalmic surgery is
      unanimously recognized. The primary anesthetic risks are associated with
      strabismus surgery, including oculocardiac reflex, postoperative nausea and
      vomiting, and postoperative pain. METHODS: This was a prospective, monocentric,
      observational study conducted in a tertiary pediatric ophthalmic unit. Our
      anesthetic protocol for strabismus surgery included postoperative nausea and
      vomiting prevention using dexamethasone and ondansetron. No drug-based prevention
      of oculocardiac reflex or local/locoregional anesthesia was employed. RESULTS: A
      total of 106 pediatric ophthalmic surgeries completed between November 2015 and
      May 2016 were analyzed. The mean patient age was 4.4 (range: 0.2-7.3, standard
      deviation: 2.4) years. Ambulatory rate was 90%. Oculocardiac reflex incidence was
      65% during strabismus surgery (34/52), 50% during congenital cataract surgery
      (4/8), 33% during intramuscular injection of botulinum toxin (1/3), and 0% during
      other procedures. No asystole occurred. Postoperative nausea and vomiting
      incidence was 9.6% after strabismus surgery (5/52) and 0% following the other
      procedures. One child was hospitalized for one night because of persistent
      postoperative nausea and vomiting. Postoperative pain generally occurred early on
      in the recovery room and was quickly controlled. Its incidence was higher in
      patients who underwent strabismus surgery (27%) than in those who underwent other
      procedures (9%). CONCLUSION: Morbidity associated with ophthalmic pediatric
      surgery is low and predominantly associated with strabismus surgery. The benefit
      risk ratio and cost-effectiveness of oculocardiac reflex prevention should be
      questioned. Our postoperative nausea and vomiting rate is low, thanks to the use
      of a well-managed multimodal strategy. Early postoperative pain is usually well
      treated but could probably be more effectively prevented.

PMID- 30280605
TI  - Foraging Behavior Patterns of Sheep and Horses Under a Mixed Species Grazing
      System.
AB  - The research objective was to assess the behavior patterns of the Polish Konik
      horse breed and the Uhruska variety of the Polish Lowland Sheep breed under a
      mixed-grazing system, and their relationship with climatic factors. The
      observation included 4 adult horses, 27 ewes with lambs and 10 primiparous ewes.
      The behavior of the animals and the weather conditions were recorded at 60-min
      intervals. Horses and sheep displayed similarities in both species-specific
      behavioral patterns and timing of grazing activity, and the duration of foraging
      sessions was mostly influenced by time of day, lower temperature and relative
      humidity. In addition, the two species showed more interest in the watering place
      in the afternoon, and drinking frequency was mainly dependent on air temperature.
      The animals that pastured together gradually began to mix, but at first, they
      remained within their species group. Both animal species can be used for
      environmental protection and landscape conservation making rational use of
      pastures within protected areas.

PMID- 30280607
TI  - Animal Welfare in Nepal.
AB  - The small densely populated country of Nepal rises from just above sea level to
      more than 8800 m and encompasses many agro-ecological zones. Rich in both nature
      and culture, livestock are integral to household and national economies. Most
      Nepalese consider the cow sacred, and slaughter is forbidden. Other nonhuman
      animals are less esteemed, slaughter is not proscribed, and many are sacrificed
      during religious festivals. Limited financial and material resources, inadequate
      feed supplies, poor access to veterinary services, absence of appropriate
      legislation, and ignoring the needs of livestock as sentient beings can
      compromise welfare and lead to inhumane treatment. This article reviews the
      welfare status of various groups (food-producing stock, work animals, street
      dogs, experimental animals, and elephants in captivity). Several animal welfare
      charities are represented. Suggestions for improved welfare are discussed, but
      the prognosis is not encouraging especially in view of the widespread struggle
      and people's own struggle for survival.

PMID- 30280606
TI  - Assessing the Feasibility of Measuring Variation in Facility Design Among
      American Childbirth Facilities.
AB  - OBJECTIVE: To assess the feasibility of quantifying variation in childbirth
      facility design and explore the implications for childbirth service delivery
      across the United States. BACKGROUND: Design has been shown to impact quality of
      care in childbirth. However, most prior studies use qualitative data to examine
      associations between the design of patient rooms and patient experience. There
      has been limited exploration of measures of unit design and its impact on care
      provision. METHOD: We recruited 12 childbirth facilities that were diverse with
      regard to facility type, location, delivery volume, cesarean delivery rate, and
      practice model. Each facility provided annotated floor plans and participated in
      a site visit or telephone interview to provide information on their design and
      clinical practices. These data were analyzed with self-reported primary cesarean
      delivery rates to assess associations between design and care delivery. RESULTS:
      We observed wide variation in childbirth unit design. Deliveries per labor room
      per year ranged from 75 to 479. The ratio of operating rooms to labor rooms
      ranged from 1:1 to 1:9. The average distance between labor rooms and workstations
      ranged from 23 to 114 ft, and the maximum distance between labor rooms ranged
      from 9 to 242 ft. More deliveries per room, fewer labor rooms per operating room,
      and longer distances between spaces were all associated with higher primary
      cesarean delivery rates. CONCLUSIONS: Clinically relevant differences in design
      can be feasibly measured across diverse childbirth facilities. The design of
      these facilities may not be optimally matched to service delivery needs.

PMID- 30280608
TI  - Oral insulin delivery by carboxymethyl-beta-cyclodextrin-grafted chitosan
      nanoparticles for improving diabetic treatment.
AB  - In this paper, a new oral insulin formulation, insulin-loaded carboxymethyl-beta
      cyclodextrin-grafted chitosan nanoparticles (insulin/CMCD-g-CS NPs), was
      fabricated by ionic crosslinking technique. The therapeutic efficacy of new
      formulation was investigated in detail. Firstly, the CMCD-g-CS was synthesized by
      EDC-mediated esterification reaction. The prepared CMCD-g-CS exhibited favourable
      loading capacity and encapsulation efficiency of drug. The release experiment in
      vitro showed that the nanocarrier could efficiently protect encapsulated insulin
      at simulated gastric environment and release drug in the simulated colonic fluid.
      The insulin/CMCD-g-CS NPs effectively promoted drug internalization into Caco-2
      cells and could reversibly open the tight junction between cells. The oral
      administration of insulin/CMCD-g-CS NPs could lastingly decrease blood sugar
      level in diabetic mice. The liver function study verified that the insulin/CMCD-g
      CS NPs had not obvious toxicity to experimental mice. Therefore, the CMCD-g-CS
      could be an effective and safe oral insulin delivery carrier for future clinical
      application. [Formula: see text] A new biocompatible polysaccharide nanoparticle
      was fabricated as oral insulin delivery carrier for improving diabetic treatment.

PMID- 30280610
TI  - STAT1 and STAT3 mutations: important lessons for clinical immunologists.
AB  - INTRODUCTION: The transcription factors signal transducer and activator of
      transcription (STAT) 1 and STAT3 fulfill fundamental functions in nonimmune and
      immune cells. The description and follow-up of patients with germline mutations
      that result in either loss-of-function or gain-of-function have contributed to
      our understanding of the pathophysiology of these regulators. Depending on the
      type of mutations, clinical symptoms are complex and can include infection
      susceptibility, immune dysregulation as well as characteristic nonimmune
      features. Areas covered: In this review, we provide an overview about mechanistic
      concepts, clinical manifestations, diagnostic process, and traditional as well as
      innovative treatment options aiming to help the clinical immunologist to better
      understand and manage these complex and rare diseases. Clinical and research
      papers were identified and summarized through PubMed Internet searches, and
      expert opinions are provided. Expert commentary: The last several years have seen
      an explosion in the clinical descriptions and pathogenesis knowledge of the
      diseases caused by GOF and LOF mutations in STAT1 and STAT3. However,
      harmonization of laboratory testing and follow-up in international cohorts is
      needed to increase our knowledge about the natural history of these disorders as
      well as the development of curative or supportive targeted therapies.

PMID- 30280609
TI  - Decoding cold ischaemia time impact on kidney graft: the kinetics of the unfolded
      protein response pathways.
AB  - The relationship between cold ischaemia time (CIT) and adverse outcome is now
      acknowledged. However, the underlying mechanisms remain to be defined, which
      slows the development of adapted therapeutics and diagnostics. We explored the
      impact of CIT in both preclinical and in vitro models of preservation. We
      determined that the endoplasmic reticulum (ER) and its stress response (unfolded
      protein response, UPR) were regulated in close association with CIT; the
      eIF2alpha-ATF4 pathway was inhibited early (1-8 h) at the detriment of cell
      survival, while the ATF6 pathway was activated late (12-24 h) and associated with
      cell death. The IRE1alpha-XBP1 branch was activated at reperfusion only if CIT
      extended beyond 8 h, and had a dual role on cell fate - deleterious through
      IRE1's RNase activity and beneficial through IRE1alpha other roles. Finally, the
      pro-apoptotic factor CHOP was a common target of both ATF6 and IRE1alpha pathways
      and was associated with elongated CIT and increased cell death. Microarray
      analysis of human transplanted kidney confirmed that UPR markers were regulated
      by CIT and that CHOP was associated with adverse outcome. We show that UPR could
      be a critical pathway explaining the relationship between CIT and graft outcome,
      highlighting the potential for UPR-based therapeutics and diagnostics to improve
      transplantation.

PMID- 30280611
TI  - Is exposure to personal music players a confounder in adolescent mobile phone use
      and hearing health studies?
AB  - OBJECTIVE: This study was performed to determine whether exposure to personal
      music players (PMPs) in the immediate morning prior to hearing testing confounds
      the association between mobile phone use and hearing thresholds of adolescents.
      DESIGN: In this cohort study of cognitive function in year 7 students (median age
      13 years, range 11-14), information regarding the weekly use of mobile phones and
      the use of PMPs was assessed by a questionnaire. Pure-tone audiometry was used to
      establish hearing thresholds for all participants. RESULTS: Among a cohort of 317
      adolescents (60.9% females), 130 were unexposed to PMP use while 33 were exposed
      to PMP use in the morning prior to hearing testing. No statistically significant
      difference in hearing threshold shifts was found between adolescents who were and
      were not exposed to PMP use prior to hearing testing. Likewise, the difference in
      the use of mobile phones according to the PMP use status was not statistically
      significant. CONCLUSION: Exposure to PMPs prior to hearing testing did not
      introduce confounding in the present study of mobile phone use and hearing loss
      among adolescents.

PMID- 30280612
TI  - Effect of progesterone/estradiol ratio on pregnancy outcome of patients with high
      trigger-day progesterone levels undergoing gonadotropin-releasing hormone
      antagonist intracytoplasmic sperm injection cycles: a retrospective cohort study.
AB  - This study investigates the predictive power of serum progesterone/estradiol
      (P/E2) level for estimating the live birth rate in patients who had a serum
      progesterone (P) rate >= 1.5 ng/mL on the human chorionic gonadotropin (hCG)
      administration day and who received the gonadotropin-releasing hormone (GnRH)
      antagonist protocol and intracytoplasmic sperm injection (ICSI). This
      retrospective cohort study included 176 cycles. The P/E2 ratio was lower in
      patients with a live birth (0.73 +/- 0.54) than those without a live birth (1.05
      +/- 1.38), but the difference was not statistically significant (p = .158).
      According to the receiver operating characteristic curve analysis of the hCG day
      P/E2 ratio, the area under the curve was 0.579 (95% confidence interval: 0.478 -
      0.680, p = .158) for predicting live birth. In conclusion, this study suggests
      that a P/E2 ratio is not a significant predictor of a live birth rate in the
      patients with an hCG-day serum progesterone level of >=1.5 ng/mL undergoing GnRH
      antagonist ICSI cycles with a fresh embryo transfer. Impact statement What is
      already known on this subject? As the progesterone (P) levels in the late
      follicular phase correlate with the estradiol (E2) levels and the increase in
      mature follicles, earlier studies have proposed the trigger-day
      progesterone/estradiol (P/E2) ratio as a potential new marker for a premature
      luteinisation and live birth success. Most of these studies were conducted on
      long agonist cycles, and found that arbitrarily defined P/E2 ratio of >1 to be
      associated with poor pregnancy outcomes. What do the results of this study add?
      This study retrospectively examines the gonadotropin-releasing hormone (GnRH)
      antagonist cycles with a trigger-day serum P value of >=1.5 ng/mL undergoing the
      intracytoplasmic sperm injection (ICSI) treatment. The receiver operating
      characteristic (ROC) curve analysis did not identify a statistically significant
      threshold value for the trigger-day P/E2 ratio that was beneficial in predicting
      a live birth. The P/E2 ratio was also lower in the cycles with a live birth than
      those without a live birth, although the difference was not statistically
      significant. What are the implications of these findings for clinical practice
      and/or further research? The trigger-day P/E2 ratio does not seem to be an
      efficient prognostic factor for a live birth in the GnRH antagonist ICSI cycles
      with a trigger-day serum progesterone level of >=1.5 ng/mL. Further studies are
      needed to clarify the association of the trigger-day P/E2 ratio and the pregnancy
      outcomes in GnRH antagonist ICSI cycles.

PMID- 30280613
TI  - Deepening Partnerships through Co-Leadership: Integrating First Voice
      Perspectives into the Recreation for Mental Health (R4MH) Project.
AB  - : With a common goal of increasing social inclusion through collaboration between
      the mental health and recreation sectors, the Recreation for Mental Health
      Project was a partnership between Dalhousie University, Recreation Nova Scotia,
      and the local Canadian Mental Health Association branch. AIMS: Central to this
      project was the meaningful involvement of individuals with First Voice
      perspectives-in this case, people with lived experience of mental health
      challenges. This paper describes key strategies used to privilege First Voice
      perspectives throughout this project. METHODS: The strategies included (a)
      advisory committee membership, (b) arts-based activities, (c) community-based
      research, and (d) co-leadership in project dissemination. FINDINGS AND
      CONCLUSION: Initial strategies related to the project's overall direction and
      research activities culminated in shared dissemination activities that fostered
      co-leadership. This co-leadership created the opportunity to intentionally
      discuss the challenges and facilitators of partnerships between people with First
      Voice experience and researchers throughout the project. SIGNIFICANCE: This
      intentional process of exploring multiple perspectives bridged notions of 'us'
      and 'them', cultivating a sense of solidarity across shared experiences of
      exclusion and agency. Key principles related to relationships, multiple
      identities, and power-sharing are synthesized.

PMID- 30280614
TI  - Economic evaluation of a pharmacogenomic multi-gene panel test to optimize anti
      hypertension therapy: simulation study.
AB  - AIMS: Hypertension is the strongest modifiable risk factor for cardiovascular
      disease, affecting 80 million individuals in the US and responsible for ~360,000
      deaths, at total annual costs of $93.5 billion. Antihypertension therapies guided
      by single genotypes are clinically more effective and may avert more adverse
      events than the standard of care of layering anti-hypertensive drug therapies,
      thus potentially decreasing costs. This study aimed to determine the economic
      benefits of the implementation of multi-gene panel guided therapies for
      hypertension from the payer perspective within a 3-year time horizon. MATERIALS
      AND METHODS: A simulation analysis was conducted for a panel of 10 million
      insured patients categorized clinically as untreated, treated but uncontrolled,
      and treated and controlled over a 3-year treatment period. Inputs included
      research data; empirical data from a 11-gene panel with known functional, heart,
      blood vessel, and kidney genotypes; and therapy efficacy and safety estimates
      from literature. Cost estimates were categorized as related to genetic testing,
      evaluation and management, medication, or adverse events. RESULTS: Multi-gene
      panel guided therapy yielding savings of $6,256,607,500 for evaluation and
      management, $908,160,000 for medications, and $37,467,508,716 for adverse events,
      after accounting for incremental genetic testing costs of $2,355,540,000. This
      represents total 3-year savings of $42,276,736,216, or a 47% reduction, and 3
      year savings of $4,228 and annual savings of $1,409 per covered patient.
      CONCLUSIONS: A precision medicine approach to genetically guided therapy for
      hypertension patients using a multi-gene panel reduced total 3-year costs by 47%,
      yielding savings exceeding $42.3 billion in an insured panel of 10 million
      patients. Importantly, 89% of these savings are generated by averting specific
      adverse events and, thus, optimizing choice of therapy in function of both safety
      and efficacy.

PMID- 30280615
TI  - Development of the Pediatric Disability Inventory-Patient Reported Outcome (PEDI
      PRO) measurement conceptual framework and item candidates.
AB  - BACKGROUND: To address the gap in patient reported outcome measures (PROMs) of
      functional performance appropriate for youth and young adults with developmental
      disabilities (DD) we developed the Pediatric Evaluation of Disability Inventory
      Patient Reported Outcome (PEDI-PRO). AIM/OBJECTIVE: We used a participatory
      process to: (1) Develop the measurement conceptual framework; (2) Identify
      discrete functional tasks to include in the PEDI-PRO; and (3) Refine item
      candidates. METHODS: We collaborated with eight youth with DD over 33 months.
      These youth and university researchers explored the construct of functional
      performance, developed and refined items, and collected and analyzed data. We
      also conducted focus groups with youth with DD (n = 62) and rehabilitation
      professionals (n = 26), and consulted with PEDI measurement experts (n = 3).
      RESULTS: Youth's understanding of their functional performance is embedded in
      their experiences participating in everyday life situations. We developed 78
      Daily Activities, 65 Social/Cognitive, and 52 Mobility item candidates that are
      linked to 11 everyday life situations to assess discrete functional tasks
      important to youth with DD and rehabilitation professionals. CONCLUSION AND
      IMPLICATIONS: As a result of our participatory development process, the PEDI
      PRO's proposed conceptual framework and item candidates are grounded in the lived
      experience of youth with DD.

PMID- 30280616
TI  - Metabolic syndrome is associated to high-sensitivity cardiac troponin T
      elevation.
AB  - INTRODUCTION: Metabolic syndrome (MetS) and high-sensitivity cardiac troponin T
      (hs-TnT) are associated with higher risk for cardiovascular diseases (CVD). Our
      aim was to assess the relation between hs-TnT elevation and MetS in a general
      population sample. MATERIALS AND METHODS: Individuals participating in an annual
      health survey program between 2010 and 2016 were included in the study. Blood
      samples including hs-TnT levels were collected. The study population was divided
      into three groups based on hs-TnT levels - undetectable (<5 ng/L), intermediate
      (5-14 ng/L) and elevated (>14 ng/L). RESULTS: A total of 5994 subjects were
      included in the study, the mean age was 48.5 and 4336 (72%) were males. Compared
      with subjects with undetectable hs-TnT the prevalence of MetS was higher in those
      with detectable and elevated levels - 392 (10%) vs. 270 (15%) and 51 (33%),
      respectively (p < 0.001). In a multivariate model adjusted for age, gender and
      multiple co-morbidities, the number of MetS components and presence of MetS were
      significantly associated with an increased risk for detectable hs-TnT levels (OR
      = 1.02 {for each component}; 95% CI [1.00-1.05], p = 0.04) and (OR = 1.13; 95% CI
      [1.07-1.2], p < 0.001) respectively. Only the waist, glucose and hypertension
      components of the MetS were significantly associated with elevated troponin.
      CONCLUSIONS: The MetS and its distinct components have a cumulative impact on hs
      TnT levels in apparently healthy subjects.

PMID- 30280617
TI  - A discrete choice experiment to investigate patient preferences for HIV testing
      programs in Bogota, Colombia.
AB  - BACKGROUND: To assess patients' preferences for HIV testing in Colombia. METHODS:
      A discrete choice experiment was used to assess preferences of patients diagnosed
      with HIV, for HIV testing in two HIV clinics in Bogota, Colombia. Patients were
      asked to choose repeatedly between two hypothetical HIV testing options that
      varied with respect to five attributes: distance to testing site,
      confidentiality, testing days, sample collection method, and the services if HIV
      positive. A random parameter model was used to analyze the data. RESULTS: A total
      of 249 questionnaires were eligible for data analysis. Respondents showed a
      preference for testing on weekdays, nobody being aware, a sample taken from the
      arm, and receiving medications through a referral. The respondents showed a high
      negative preference for many people being aware, followed by testing during the
      weekend and home testing. Subgroup analyses by gender and prior testing history
      did not reveal significant differences. CONCLUSION: This study suggests that
      patients' preferences for HIV testing focused especially on confidentiality,
      availability during weekdays, and using a sample from the arm. This information
      could be useful to improve uptake of HIV testing in Bogota, Colombia.

PMID- 30280618
TI  - Stereotactic body radiation therapy for mediastinal lymph node metastases: how do
      we fly in a 'no-fly zone'?
AB  - PURPOSE: To evaluate the treatment-induced toxicity (as primary endpoint) and the
      efficacy (as secondary endpoint) of stereotactic body radiation therapy (SBRT) in
      the treatment of mediastinal lymph nodes (LNs) in the so-called no-fly zone (NFZ)
      in cancers with various histology. MATERIAL AND METHODS: Forty-two patients were
      retrospectively analyzed. Institutional dose/volume constraints for organs at
      risk (OARs) derived by published data were strictly respected. The correlation
      between treatment-related variables and toxicity was investigated by logistic
      regression, Chi-squared test or Fisher's exact test. Overall survival (OS), cause
      specific survival (CSS), progression-free survival (PFS) and local control (LC)
      were collected from the follow-up reports. The impact of potential predictive
      factors on LC, PFS and OS were estimated by Cox proportional-hazard regression.
      RESULTS: Median follow-up time was 16 months (range 1-41). Four patients had
      esophageal G1 toxicity. Ten and six patients had G1 and G2 pulmonary toxicity,
      respectively. Treatment site and irradiation technique were significantly
      correlated with G >= 2 and G >= 1 toxicity, respectively. OS probability at 19
      months was 88.3% and corresponded to CSS. LC probability at 16 months was 66.3%
      (median LC duration: 22 months, range 1-41). Fifteen patients (35.7%) were
      disease-free at 25 months (median time, range 1-41). The biologically effective
      dose (BED) and the target dose coverage indexes were significantly correlated
      with LC. CONCLUSIONS: SBRT can be considered as a safe treatment option for
      selected patients with oligo-metastases/recurrences in the NFZ, if strict
      dose/volume constraints are applied.

PMID- 30280619
TI  - Disparities in colorectal cancer between Northern and SouthernSweden - a report
      from the new RISK North database.
AB  - BACKGROUND: Geographic cancer health disparities have been reported in Sweden.
      The disparities are not fully understood, but may be attributed to differences in
      exposure to risk factors as well as differences in health care, socioeconomics
      and demography. The aim of this study was to describe the new nationwide
      population based RISK North database and its potential by analysing health
      disparities in colorectal cancer between Northern and Southern Sweden. METHODS:
      Cancer-specific data from the National Cancer Quality Registers for colorectal,
      gastric and oesophageal cancer and brain tumours were linked to several
      nationwide registers hereby creating a new database - RISK North. To exemplify
      the potential of RISK North, we analyzed differences in colorectal cancer
      incidence, mortality and survival in relation to gender, age, cohabitation and
      education between Northern and Southern Sweden 2007-2013. RESULTS: In colon
      cancer, the age-adjusted incidence per 100.000 was lower in Northern than
      Southern Sweden, 35.9 in the North vs. 41.1 in the South (p < .01); mortality
      rates were 11.0 vs. 12.2 (p < .01). For rectal cancer, incidence rates were 17.6
      vs. 19.7 (p < .01) and mortality rates 5.33 vs. 5.89 (p = .07), respectively. The
      largest difference in incidence was demonstrated for colon cancer among
      individuals >79 years old (190. vs. 237, i.e., ~20%). Survival in colon cancer
      was higher in Southern Sweden, HR 0.92 (0.87-0.98) adjusted for age, gender, co
      habiting, education and m-stage at diagnosis. No difference in survival was seen
      for rectal cancer. CONCLUSIONS: The new RISK North database enabled analysis of
      cancer disparities between Northern and Southern Sweden. The incidence of
      colorectal cancer were lower in the North of Sweden whereas colon cancer survival
      was higher in the South. These differences can be further analysed utilising the
      RISK North database.

PMID- 30280620
TI  - National practice patterns of proton versus photon therapy in the treatment of
      adult patients with primary brain tumors in the United States.
AB  - OBJECTIVES: To examine patterns of care associated with the administration of
      proton versus photon therapy for adult patients with primary brain tumors in a
      large national cohort from the United States. METHODS: The National Cancer
      Database (NCDB) was queried for newly diagnosed primary brain tumors (2004-2014)
      in adult patients aged 18 and older receiving proton or photon radiotherapy.
      Clinical features, patient demographics and treatment parameters were extracted.
      Differences between groups were assessed using multivariable logistic regression
      analysis. RESULTS: In total, 73,073 patients were analyzed (n = 72,635 [99.4%]
      photon therapy, n = 438 [0.6%] proton therapy). On multivariable analysis of
      photon versus proton therapy, several factors predicted for receipt of proton
      therapy, including younger age (p = .041), highest income quartile (p = .007),
      treatment at academic institutions (p < .001), in regional facilities outside the
      Midwest/South (p < .001), diagnosis in more recent years (p = .003), fewer
      comorbidities (p < .001) and non-glioblastoma histology (p < .001). CONCLUSIONS:
      There are several significant socioeconomic variables that influence receipt of
      proton therapy for primary brain tumors. Although not implying causation, the
      socioeconomic findings discovered herein should be taken into account when
      delivering cancer care to all patients.

PMID- 30280621
TI  - Everyday managing and living with autoimmune Addison's disease: Exploring
      experiences using photovoice methods.
AB  - People with rare diseases are a minority group that faces risks for healthcare
      and work inequities because knowledge and resources on how to systematically
      support health or working life are limited. Integrating voices of persons living
      with rare diseases are an important aspect in inclusive and relevant healthcare
      practices. This study sought to actively involve persons with autoimmune
      Addison's disease (AAD), a rare condition, in exploring challenges and
      possibilities situated in everyday life. Photovoice methods were utilized to
      incorporate experiences through photographic documentation and group discussions
      with five persons over seven weeks. Data generated from group sessions were
      visually analyzed or transcribed and analyzed with thematic analysis. Five themes
      emerged: Individual and fine tuning in everyday life; It is not how it was; The
      power of knowledge and support; Becoming the expert in an uncertain context; and,
      Finding balance and paving new ways. The findings showed that everyday life with
      AAD was more complex than earlier portrayed; entailing several barriers and
      negotiations. In order to meet the needs of persons with AAD, more extensive and
      relevant information, support and self-management education is needed. Moreover,
      a complementary focus on everyday life to promote their health and wellbeing is
      also important.

PMID- 30280622
TI  - Re-irradiation for painful bone metastases using stereotactic body radiotherapy.
AB  - PURPOSE: Stereotactic body radiotherapy (SBRT) is expected to achieve safe and
      effective re-irradiation for painful bone metastases. This study aimed to clarify
      the efficacy of re-irradiation using SBRT for painful bone metastases. METHODS:
      Prospective database at our institution for the period between September 2013 and
      December 2017 were retrospectively reviewed for patients with: (1) painful bone
      metastases; (2) history of radiotherapy to the metastasis; and (3) SBRT performed
      as re-irradiation. Pain response, pain failure-free duration, analgesics
      medications, and adverse events were evaluated. Pain was evaluated using the
      Numerical Rating Pain Score, and pain response was evaluated based on
      International Consensus Pain Response Endpoints. Best response during follow-up
      was noted. Patients with complete or partial response were defined as showing
      pain response, and patients with pain progression were defined as showing pain
      failure. Adverse events were evaluated based on the RTOG/EORTC Late Radiation
      Morbidity Scoring Schema. RESULTS: Sixty-six patients selected from our database
      showed: median age, 65 years (range, 33-82 years); ECOG performance status, 0
      1/2/3/4, 51/10/3/2; lesion histopathology, rectal/lung/renal/thyroid/other
      cancer, 13/11/9/5/28; median previous irradiated dose, 30 Gy (range, 8-70.4 Gy);
      median interval from latest irradiation, 21 months (range, 4-192 months);
      prescribed dose for SBRT, 24 Gy in 2 fractions/30 Gy in 5 fractions/35 Gy in 5
      fractions, 51/13/2. Median follow-up after SBRT was 10 months (range, 1-37
      months). Fifty-seven patients achieved pain response (86%). The 1-year pain
      failure-free rate was 55%. Median pain failure-free duration was 13 months
      (range, 1-24 months). Grade 4 adverse events were observed in six patients
      (vertebral compression fracture, n = 5; radiation myelopathy, n = 1). No other
      toxicities of Grade 3 or greater were encountered. CONCLUSIONS: Re-irradiation
      SBRT has potential to achieve good response and long-term pain control for
      painful bone metastases. Prospective analysis is necessary to confirm the safety
      and efficacy of SBRT as re-irradiation.

PMID- 30280623
TI  - Dose painting for re-irradiation of head and neck cancer.
AB  - BACKGROUND: For patients with recurrent or second primary disease, re-irradiation
      can be challenging due to overlap with previously irradiated volumes. Dose
      painting may be attractive for these patients, as the focus is on delivering
      maximal dose to areas of high tumor activity. Here, we compare dose painting by
      contours (DPBC) treatment plans based on 18F-fluorodeoxyglucose (FDG) positron
      emission tomography (PET) with conventional plans. MATERIAL AND METHODS: We
      included 10 patients with recurrent or second primary head and neck cancer (HNC)
      eligible for re-irradiation. Our conventional re-irradiation regimen is
      hyperfractionated radiotherapy 1.5 Gy twice daily over 4 weeks, giving a total
      dose of 60 Gy. For DPBC, we defined two prescription volumes, PV33 and PV66,
      corresponding to 33 and 66% of the highest FDG uptake in the tumor. The clinical
      target volume (CTV) prescription dose was 60 Gy, PV33; 65-67 Gy and PV66; 70-73
      Gy. The DPBC plan is to be given the first 20 fractions and the conventional plan
      the last 20 fractions. Dose to organs at risk (OARs) were compared for DPBC and
      conventional treatment. By summation of the initial curative plan and the re
      irradiation plan, we also evaluated differences in dose to the 2 ccm hot spot
      (D2cc). RESULTS: We achieved DPBC plans with adequate target coverage for all 10
      patients. There were no significant differences in OAR doses between the standard
      plans and the DPBC plans (p=.7). Summation of the initial curative plan and the
      re-irradiation plan showed that the median D2cc increased from 130 Gy (range 113
      132 Gy; conventional) to 140 Gy (range 115-145 Gy; DPBC). CONCLUSIONS: Our
      proposed DPBC could be straightforwardly implemented and all plans met the
      objectives. Re-irradiation of HNC with DPBC may increase tumor control without
      more side effects compared to conventional radiotherapy.

PMID- 30280624
TI  - Increasing kidney cancer incidence and survival in Estonia: role of age and
      stage.
AB  - BACKGROUND: Kidney cancer rates in Estonia are high. The study aimed to examine
      long-term trends in kidney cancer incidence, mortality and survival in Estonia,
      with special focus on age, birth cohorts, morphology and TNM stage. MATERIAL AND
      METHODS: Estonian Cancer Registry provided data on all incident cases of kidney
      cancer (ICD-10 C64), diagnosed in adults (age >=15 years) in Estonia during 1995 
      2014. Relative survival ratios (RSR) were calculated and excess hazard ratios of
      dying were estimated with gender, age, period of diagnosis and TNM stage as
      independent variables. Joinpoint regression modeling was used to calculate
      estimated annual percentage change for incidence (1970-2014) and mortality (1995
      2016) trends. Age-specific incidence rates were presented by birth cohort and
      period of diagnosis. RESULTS: Incidence increased significantly in both sexes,
      with the steepest rise seen for localized cancer. Cohort effects were pronounced
      particularly in men, while period effects were seen from the mid-1980s to mid
      1990s in both sexes. Age-standardized five-year RSR for total kidney cancer
      increased by 13 percentage units (from 53% to 65%) over the study period; the
      increase was larger for renal cell carcinoma (from 63% to 78%). Survival
      increases of about five percentage units were seen for stages I/II and III. Age
      and gender were not associated with excess risk of dying from renal cell
      carcinoma after adjusting for stage. CONCLUSION: Estonia is currently among
      countries with the highest incidence of kidney cancer. The results suggest a
      combined effect of changing risk profiles in successive birth cohorts and
      increasing diagnostic activity around 1990. Large survival increase can mostly be
      attributed to earlier detection, but improved diagnosis and treatment have
      probably influenced stage-specific survival. High proportion of tumors with
      unspecified morphology and those with unknown stage among the elderly warrants
      further investigation of diagnostic and treatment practices.

PMID- 30280625
TI  - Frailty status but not age predicts complications in elderly cancer patients: a
      follow-up study.
AB  - OBJECTIVES: The purposes were to investigate the health status of elderly cancer
      patients by comprehensive geriatric assessment (CGA) and to compare the
      complications with respect to baseline CGA and to evaluate the need for geriatric
      interventions in an elderly cancer patients' population. MATERIAL: Patients aged
      >=70 years with lung cancer (LC), cancer of the head and neck (HNC), colorectal
      cancer (CRC), or upper gastro-intestinal cancer (UGIC) are referred to the
      Department of Oncology for cancer treatment. METHODS: CGA was performed prior to
      cancer treatment and addressed the following domains: Activities of daily living
      (ADL), instrumental ADL (IADL), comorbidity, polypharmacy, nutrition, cognition,
      and depression. Complications, defined as dose reduction and discontinuation of
      treatment due to grade 3-4 toxicity, hospital admission, shift to palliative
      treatment, or death within 90 days, were identified from the medical files.
      Patients were classified as fit, vulnerable, or frail by CGA. PRINCIPAL RESULTS:
      Patients (N = 217) with a median age of 75 years (range: 70-93 yeas) were
      included: 13% were fit, 35% vulnerable, and 52% frail. CGA significantly
      predicted admittance to hospital in frail and vulnerable patients compared to fit
      patients: risk ratio (RR) 2.12 (95% CI: 1.01; 4.46). Vulnerable and frail
      patients had higher absolute risk of death within 90 days compared to fit
      patients: 7% and 23% versus 0%. HR for death within 90 days in frail patients as
      compared to vulnerable patients was 3.50 (95% CI: 1.34; 9.15). More frail
      patients (88%) needed geriatric interventions than the vulnerable (46%) and fit
      patients (32%). Major conclusion: Few elderly cancer patients seem to be fit. CGA
      predicts admittance to hospital in a population of elderly patients with mixed
      cancer diseases. Frail and vulnerable patients have higher risk of death within
      90 days as compared to fit patients.

PMID- 30280626
TI  - Comparative treatment planning study for mediastinal Hodgkin's lymphoma: impact
      on normal tissue dose using deep inspiration breath hold proton and photon
      therapy.
AB  - BACKGROUND: Late effects induced by radiotherapy (RT) are of great concern for
      mediastinal Hodgkin's lymphoma (HL) patients and it is therefore important to
      reduce normal tissue dose. The aim of this study was to investigate the impact on
      the normal tissue dose and target coverage, using various combinations of
      intensity modulated proton therapy (IMPT), volumetric modulated arc therapy
      (VMAT) and 3-dimensional conformal RT (3D-CRT), planned in both deep inspiration
      breath hold (DIBH) and free breathing (FB). MATERIAL AND METHODS: Eighteen
      patients were enrolled in this study and planned with involved site RT. Two
      computed tomography images were acquired for each patient, one during DIBH and
      one during FB. Six treatment plans were created for each patient; 3D-CRT in FB,
      3D-CRT in DIBH, VMAT in FB, VMAT in DIBH, IMPT in FB and IMPT in DIBH. Dosimetric
      impact on the heart, left anterior descending (LAD) coronary artery, lungs,
      female breasts, target coverage, and also conformity index and integral dose
      (ID), was compared between the different treatment techniques. RESULTS: The use
      of DIBH significantly reduced the lung dose for all three treatment techniques,
      however, no significant difference in the dose to the female breasts was
      observed. Regarding the heart and LAD doses, large individual variations were
      observed. For VMAT, the mean heart and LAD doses were significantly reduced using
      DIBH, but no significant difference was observed for 3D-CRT and IMPT. Both IMPT
      and VMAT resulted in improved target coverage and more conform dose distributions
      compared to 3D-CRT. IMPT generally showed the lowest organs at risk (OAR) doses
      and significantly reduced the ID compared to both 3D-CRT and VMAT. CONCLUSIONS:
      The majority of patients benefited from treatment in DIBH, however, the impact on
      the normal tissue dose was highly individual and therefore comparative treatment
      planning is encouraged. The lowest OAR doses were generally observed for IMPT in
      combination with DIBH.

PMID- 30280627
TI  - Life filming as a means of participatory approach together with older community
      dwelling persons regarding their local environment.
AB  - BACKGROUND: The potential to influence the design of one's local environment is
      especially important to older people since age-related problems, in combination
      with a less supportive environment, can prevent the performance of meaningful
      activities. It is unclear how best to tailor a participatory approach to support
      the task of collaborating with older persons about their local environment. Life
      filming was used in such a project. OBJECTIVE: To describe Life filming as a
      means of participatory approach in relation to older community-dwelling persons
      and the design of their local environment. MATERIAL AND METHOD: A descriptive
      single case study. Data were generated through field notes and memos, and
      analyzed utilizing thematic analysis. Participants have validated the findings.
      FINDINGS: Five themes describe central aspects of Life filming in the given
      context: Anchoring the concept of participation, Practical application of Life
      filming, The film as a product, Making a real difference, and An identity as a
      capable older person. CONCLUSION: Life filming supported participation, both as a
      process and an outcome. It had benefits on multiple levels: for the individual
      person, for older persons as a group, and for the municipality. Life filming
      could constitute a useful digital tool for practice when a participatory approach
      is desired.

PMID- 30280628
TI  - Real-world use of PCSK9 inhibitors: A single-center experience.
AB  - Objective Hyperlipidemia is an important risk factor for atherosclerotic
      cardiovascular disease. Many patients are intolerant to or have limited benefit
      from statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors
      have been approved for treating hyperlipidemia in these patients. We sought to
      investigate the impact of these medications in a real-world cardiology practice.
      Methods This was a retrospective study of 17 patients with either heterozygous
      familial hypercholesterolemia or established atherosclerotic cardiovascular
      disease with low-density lipoprotein cholesterol (LDL-C) levels above the
      treatment target despite maximally tolerated statins. Baseline lipid profile was
      compared with a repeat lipid profile obtained 4 to 6 weeks after initiating
      treatment with a PCSK9 inhibitor. Results The average duration of PCSK9 inhibitor
      treatment was 10.7 months. Lipid profile comparison showed that total cholesterol
      decreased from 243 +/- 72 to 148 +/- 39 (mg/dL) (39% reduction), triglycerides
      decreased from 185 +/- 86 to 149 +/- 62 (mg/dL) (19.5% reduction), high-density
      lipoprotein cholesterol increased from 56 +/- 20 to 62 +/- 26 (mg/dL) (10.7%
      increase), and LDL-C decreased from 154 +/- 30 to 57 +/- 32 (mg/dL) (63%
      reduction) from baseline. Conclusions PCSK9 inhibitors as add-on therapy to
      maximally tolerated statins resulted in an approximately 63% reduction in LDL-C.

PMID- 30280629
TI  - Creating opportunities for occupational development using the concerns report
      method.
AB  - BACKGROUND: Little research has focused on working with communities to promote
      and support children's occupational development. AIM/OBJECTIVE: We used the
      Concerns Report Method (CRM) to identify community supports for parents with
      young children that could enhance children's occupational development. MATERIAL
      AND METHOD: We conducted interviews/focus groups with parents (n = 29) and
      service providers (n = 11). We used content analysis to identify four themes:
      availability, barriers and facilitators, parent/child transitions, and making
      connections. The themes were used to create a concerns report survey for parents
      and service providers. A random sample of parents (n = 319) and convenience
      sample of service providers (n = 47) in one community area of a Canadian urban
      center completed the on-line survey. We held a community forum to review the
      results and identify solutions for action. RESULTS: Parents' highest priorities
      included childcare, supports in community schools, preschool programs, and
      supports in one location. Service providers highest priorities included:
      identification of developmental concerns; parenting education; programs for
      fathers, programs that offer child care, a doctor, and child care. CONCLUSIONS:
      Service providers need to engage parents and consider parents' perspectives when
      planning services to ensure community supports will meet parent identified needs.
      SIGNIFICANCE: Using community-based participatory research approaches,
      occupational therapists can contribute to children's occupational development.

PMID- 30280630
TI  - Caregivers of patients receiving long-term treatment with a tyrosine kinase
      inhibitor (TKI) for gastrointestinal stromal tumour (GIST): a cross-sectional
      assessment of their distress and burden.
AB  - BACKGROUND: TKIs are a long-term treatment for GIST, and may have an impact on
      caregivers. MATERIAL AND METHODS: For this cross-sectional study, patients and
      caregivers were both included when patients had been treated with TKIs for at
      least six months. Caregivers completed questionnaires including demographics,
      distress (Hospital Anxiety and Depression scale), burden (Self-Perceived Pressure
      from Informal Care) general health (RAND-36), comorbidity (Self-administered
      Comorbidity Questionnaire), social support (Social Support List - Discrepancies)
      and marital satisfaction (Maudsley Marital Questionnaire). Patients completed
      similar questionnaires, without 'burden'. We conducted analyses to explore
      differences between caregivers with low/moderate versus high levels of burden and
      low versus high levels of distress. RESULTS: Sixty-one out of seventy-one
      eligible couples (84%) were included in the analysis. The median age of the
      caregivers was 60 years; 66% were female and 78% were the patients' spouse. The
      median age of the patients was 66 years; 43% were female. Caregivers experienced
      high levels of burden and distress in 10% and 23%, respectively. Caregivers with
      high levels of burden perceived significantly lower mental health, less vitality,
      lower general health and high levels of distress. Significantly higher levels of
      burden were found in non-spouses, caregivers of patients with more treatment
      related side-effects, caregivers who spent more hours caring, and those caring
      for more than one person. For distress, caregivers with high levels of distress
      perceived significantly more burden, lower social functioning, more role physical
      and emotional problems, lower mental health, less vitality and lower general
      health. Furthermore, high levels of distress were found in caregivers of more
      dependent patients and those caring for more than one person. CONCLUSIONS:
      Caregivers of the patients with GIST treated with TKI are managing well. There is
      a small, vulnerable group of caregivers with high levels of burden and/or
      distress, show more health-related problems, both physical and mental, and
      require adequate support.

PMID- 30280631
TI  - Simulated dosimetric impact of online replanning for stereotactic body radiation
      therapy of lymph node oligometastases on the 1.5T MR-linac.
AB  - PURPOSE: Online 1.5T MR imaging on the MR-linac gives better target visualization
      compared to CBCT and facilitates online adaptive treatment strategies including
      daily replanning. In this simulation study, the dosimetric impact of online
      replanning was investigated for SBRT of lymph node oligometastases as a method
      for correcting for inter-fraction anatomical changes. METHODS: Pre-treatment
      plans were created for 17 pelvic and para-aortic lymph nodes, with 3 and 8 mm PTV
      margins reflecting our clinical practice for lymph nodes with good and poor
      visibility on CBCT. The dose-volume parameters of the pre-treatment plans were
      evaluated on daily anatomy as visible on the repeated MRIs and compared to online
      replanning. RESULTS: With online MRI-based replanning significant dosimetric
      improvements are obtained for the rectum, bladder, bowel and sigmoid without
      compromising the target dose. The amount of unintended violations of the dose
      constraints for target and surrounding organs could be reduced by 75% for 8 mm
      and 66% for 3 mm PTV margins. CONCLUSION: The use of online replanning based on
      the actual anatomy as seen on repeated MRI compared to online position correction
      for lymph node oligometastases SBRT gives beneficial dosimetric outcomes and
      reduces the amount of unplanned violations of dose constraints.

PMID- 30280632
TI  - Neurocognitive Disorder Diagnoses Matter: A Brief Report on Caregiver Appraisal
      of Driving Ability.
AB  - BACKGROUND: Age-associated neurocognitive disorders (NCDs) are associated with
      progressive loss of abilities for instrumental activities of daily living,
      including driving. This study assesses the impact of NCD diagnosis, while
      controlling for reported level of cognitive impairment, on family caregiver
      judgment of driving safety. METHOD: An intervention sample of 152
      intergenerational caregivers who assist an older adult with medical tasks was
      used. Caregiver's pre-intervention response to a single item of confidence in the
      older adult driving was used to determine judgment of driving ability. Cognitive
      impairment was assessed using caregivers' report for Clinical Dementia Rating
      (CDR) Sum of Boxes score. RESULTS: Older adults with a diagnosis were rated as
      less capable of driving safely than those without a diagnosis, while controlling
      for reported level of cognitive impairment. CONCLUSION: Results of this study
      highlight the importance of NCD diagnosis on caregiver judgments. Results of this
      study have implications for health care and driving safety.

PMID- 30280633
TI  - Survival and prognostic factors of pulmonary oligometastases treated with
      stereotactic body radiotherapy.
AB  - BACKGROUND: Stereotactic body radiotherapy (SBRT) for pulmonary oligometastatic
      disease achieves excellent treatment outcomes in terms of local control and
      toxicity. Patients treated with SBRT are often elderly and have multiple co
      morbidities. This subset of patients may experience different survival as
      compared to young and fit patients subjected to radical metastasectomies. The
      purpose of this retrospective study was to evaluate OS and identify factors
      associated with OS for inoperable pulmonary oligometastases treated with SBRT.
      MATERIAL AND METHODS: Criteria used for selection of patients with
      oligometastases included: metastases limited to <=2 organs and in total <=5
      metastases at the time of treatment. Peripheral tumors were treated with 51 Gy to
      60 Gy in three fractions or a single fraction of 30 Gy. Central tumors received a
      dose of 45-60 Gy in 5-8 fractions. Survival probabilities were estimated by means
      of Kaplan-Meier method and the relation between potential prognostic factors and
      OS was studied by means of Cox regression analyses. RESULTS: In this study, 327
      inoperable pulmonary oligometastases in 206 patients were treated with SBRT from
      the year 2005 to 2015. Primary sites of pulmonary oligometastases included
      colorectal carcinoma (n = 118), lung carcinoma (n = 36), melanoma (n = 11),
      sarcoma (n = 10), breast carcinoma (n = 7), and other tumors sites (n = 24).
      Median follow-up was 26 months. Median survival was 33 months. The 2-year and 5
      year OS rates were 63% and 30%, respectively. On univariate analysis synchronous
      oligometastases (HR 0.59) and colorectal primary (HR 0.64) were associated with
      improved OS. On multivariable analysis synchronous oligometastases (HR 0.56),
      colorectal primary (HR 0.62) and tumor size <3 cm (HR 0.68) were independently
      associated with OS. CONCLUSIONS: SBRT to pulmonary oligometastases was associated
      with a 2-year OS of 63%. Tumor size <3 cm and colorectal primary tumors
      experienced improved OS compared to tumors >3 cm and non-colorectal primary
      tumors.

PMID- 30280634
TI  - The Impact of Adverse Childhood Events on the Sexual and Mental Health of Women
      Experiencing Intimate Partner Violence.
AB  - Women experiencing intimate partner violence (IPV) are at an increased risk of
      engaging in sexual risk behaviors and experiencing depressive and posttraumatic
      stress symptoms. Adverse childhood events (ACEs) can put women at increased risk
      of poor sexual and mental health. Women experiencing IPV report ACEs, but few
      studies have examined the heterogeneity in women's experiences of ACEs and its
      effects on sexual and mental health. Therefore, the current study used latent
      profile analysis to identify profiles of ACEs (i.e., witnessing maternal and
      paternal IPV victimization; childhood physical, sexual, and emotional abuse; and
      physical and emotional neglect) and their association with sexual risk behaviors
      and depressive and posttraumatic stress symptoms. Women experiencing IPV aged 18
      to 58 years ( N = 212) were recruited from community establishments and completed
      face-to-face, computer-assisted interviews. Three profiles were identified: Low
      ACEs class ( n = 115), Moderate ACEs class ( n = 62), and High ACEs class ( n =
      35). Path analyses revealed that profiles of ACEs directly predicted women's IPV
      victimization severity and depressive and posttraumatic stress symptoms.
      Secondary and tertiary mental health interventions may be more effective if the
      heterogeneity in women's ACEs is addressed by integrating intervention strategies
      specific to these ACE subgroups.

PMID- 30280637
TI  - Is a delay in the introduction of human papillomavirus-based cervical screening
      affordable?
AB  - Objective It often takes considerable time for sufficient evidence to accumulate
      to support implementation of new methods in routine screening. Where national
      screening programmes are already effective, switching to a more sensitive
      screening test may not be a priority. Although risk associated with overly rapid
      implementation exists, postponement is also associated with a (to date
      unquantified) missed opportunity to prevent deaths. This risk tends not to be
      addressed where effective screening methods are already in use. We here estimate
      the monetary value of a one-year delay in replacing cytology cervical screening
      with human papillomavirus testing. Methods Using a previously validated model, we
      calculated the number of incident and fatal cervical cancers that would be
      diagnosed by 2030 in England, under the assumption that human papillomavirus
      testing replaces cytology in 2020 rather than 2019, and the monetary value of the
      quality-adjusted life years lost in preventable cases. Results A one-year delay
      in the implementation of human papillomavirus screening would miss the
      opportunity to prevent 581 cases of cervical cancer, and lead to a loss of 1595
      quality-adjusted life years (3.5% discount rate) with a monetary value of L32
      million (at L20,000 per quality-adjusted life year). Conclusion This is a
      measurable loss and should be considered in prioritising decision-making in
      screening.

PMID- 30280638
TI  - Region-Specific Phenotypes of Microglia: The Role of Local Regulatory Cues.
AB  - Microglia are ubiquitous, macrophage like cells within the central nervous system
      (CNS) that play critical roles in supporting neuronal health and viability. They
      can also influence neuronal membrane properties and synaptic connectivity,
      positioning microglia as key cellular players in both physiological and
      pathological contexts. Microglia have generally been assumed to be equivalent
      throughout the CNS, but accumulating evidence indicates that their properties
      vary substantially across distinct CNS regions. In comparison to our
      understanding of neuronal diversity and its functional importance, our knowledge
      about causes and consequences of microglial regional heterogeneity is extremely
      limited. To fully understand how microglia influence the function of specific
      neuronal populations and shape heightened susceptibility of some neurons to
      damage and disease, greater focus on microglial heterogeneity is needed.

PMID- 30280636
TI  - Mouse mast cells and mast cell proteases do not play a significant role in acute
      tissue injury pain induced by formalin.
AB  - Subcutaneous formalin injections are used as a model for tissue injury-induced
      pain where formalin induces pain and inflammation indirectly by crosslinking
      proteins and directly through activation of the transient receptor potential A1
      receptor on primary afferents. Activation of primary afferents leads to both
      central and peripheral release of neurotransmitters. Mast cells are found in
      close proximity to peripheral sensory nerve endings and express receptors for
      neurotransmitters released by the primary afferents, contributing to the
      neuro/immune interface. Mast cell proteases are found in large quantities within
      mast cell granules and are released continuously in small amounts and upon mast
      cell activation. They have a wide repertoire of proposed substrates, including
      Substance P and calcitonin gene-related peptide, but knowledge of their in vivo
      function is limited. We evaluated the role of mouse mast cell proteases (mMCPs)
      in tissue injury pain responses induced by formalin, using transgenic mice
      lacking either mMCP4, mMCP6, or carboxypeptidase A3 (CPA3), or mast cells in
      their entirety. Further, we investigated the role of mast cells in heat
      hypersensitivity following a nerve growth factor injection. No statistical
      difference was observed between the respective mast cell protease knockout lines
      and wild-type controls in the formalin test. Mast cell deficiency did not have an
      effect on formalin-induced nociceptive responses nor nerve growth factor-induced
      heat hypersensitivity. Our data thus show that mMCP4, mMCP6, and CPA3 as well as
      mast cells as a whole, do not play a significant role in the pain responses
      associated with acute tissue injury and inflammation in the formalin test. Our
      data also indicate that mast cells are not essential to heat hypersensitivity
      induced by nerve growth factor.

PMID- 30280639
TI  - Digital Intimate Partner Violence Among Peruvian Youths: Validation of an
      Instrument and a Theoretical Proposal.
AB  - The present study presents psychometric information on a new instrument, the
      Digital Intimate Partner Violence Questionnaire (DIPVQ), and explores the
      similitudes and differences between in-person and digital-based abuses (those
      that involve the use of information and communication technologies [ICTs]). In
      all, 449 Peruvian students took part in the study ( X = 21.2 years; SD = 4.3
      years; 73% women). DIPVQ structure was determined by carrying out an exploratory
      factor analysis (EFA) with polychoric correlation matrices and oblique rotation.
      In-person violence was assessed using the Dating Violence Questionnaire (DVQ) and
      self-labeling questions (e.g., feeling trapped, afraid, and abused). Relationship
      satisfaction was assessed using the Perceived Relationship Quality Components
      Short Form (PRQC-SF). EFA showed a two-scale structure for the DIPVQ: control
      centered cyberabuse ( N = 5; control, monitoring, and identity theft; EAP alpha =
      .96) and damage-centered cyberabuse ( N = 7; unwanted sexual contents,
      blackmailing, and causing debts throughout ICT; Expected-A-Posteriori alpha =
      .97). DIPVQ had direct relationship to DVQ and self-labeling ( p < .001; d = 0.38
      1.18), and inverse to PRQC-SF ( p = .11; d = .22-.33). Behaviors such as
      impersonation and monitoring were reported by more than 20% of participants.
      Online and offline victimization coexist in 42% of cases, while 3.6% of
      aggressions happened exclusively via ICT. DIPVQ is a valid and reliable measure
      of digital victimization. The control-centered scale had a higher frequency,
      although the damage-centered scale had stronger relationship to feeling afraid
      and abused. While previous literature has classified online aggressions regarding
      their aesthetic appearance, it seems that their functional value (control vs.
      hurting) could provide a better framework for understanding these aggressions.

PMID- 30280640
TI  - Transcatheter Mitral-Valve Repair in Patients with Heart Failure.
AB  - BACKGROUND: Among patients with heart failure who have mitral regurgitation due
      to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral
      valve repair may improve their clinical outcomes. METHODS: At 78 sites in the
      United States and Canada, we enrolled patients with heart failure and moderate-to
      severe or severe secondary mitral regurgitation who remained symptomatic despite
      the use of maximal doses of guideline-directed medical therapy. Patients were
      randomly assigned to transcatheter mitral-valve repair plus medical therapy
      (device group) or medical therapy alone (control group). The primary
      effectiveness end point was all hospitalizations for heart failure within 24
      months of follow-up. The primary safety end point was freedom from device-related
      complications at 12 months; the rate for this end point was compared with a
      prespecified objective performance goal of 88.0%. RESULTS: Of the 614 patients
      who were enrolled in the trial, 302 were assigned to the device group and 312 to
      the control group. The annualized rate of all hospitalizations for heart failure
      within 24 months was 35.8% per patient-year in the device group as compared with
      67.9% per patient-year in the control group (hazard ratio, 0.53; 95% confidence
      interval [CI], 0.40 to 0.70; P<0.001). The rate of freedom from device-related
      complications at 12 months was 96.6% (lower 95% confidence limit, 94.8%; P<0.001
      for comparison with the performance goal). Death from any cause within 24 months
      occurred in 29.1% of the patients in the device group as compared with 46.1% in
      the control group (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P<0.001).
      CONCLUSIONS: Among patients with heart failure and moderate-to-severe or severe
      secondary mitral regurgitation who remained symptomatic despite the use of
      maximal doses of guideline-directed medical therapy, transcatheter mitral-valve
      repair resulted in a lower rate of hospitalization for heart failure and lower
      all-cause mortality within 24 months of follow-up than medical therapy alone. The
      rate of freedom from device-related complications exceeded a prespecified safety
      threshold. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079 .).

PMID- 30280635
TI  - Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer.
AB  - BACKGROUND: Standard first-line therapy for metastatic, squamous non-small-cell
      lung cancer (NSCLC) is platinum-based chemotherapy or pembrolizumab (for patients
      with programmed death ligand 1 [PD-L1] expression on >=50% of tumor cells). More
      recently, pembrolizumab plus chemotherapy was shown to significantly prolong
      overall survival among patients with nonsquamous NSCLC. METHODS: In this double
      blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, 559 patients with
      untreated metastatic, squamous NSCLC to receive 200 mg of pembrolizumab or saline
      placebo for up to 35 cycles; all the patients also received carboplatin and
      either paclitaxel or nanoparticle albumin-bound [nab]-paclitaxel for the first 4
      cycles. Primary end points were overall survival and progression-free survival.
      RESULTS: After a median follow-up of 7.8 months, the median overall survival was
      15.9 months (95% confidence interval [CI], 13.2 to not reached) in the
      pembrolizumab-combination group and 11.3 months (95% CI, 9.5 to 14.8) in the
      placebo-combination group (hazard ratio for death, 0.64; 95% CI, 0.49 to 0.85;
      P<0.001). The overall survival benefit was consistent regardless of the level of
      PD-L1 expression. The median progression-free survival was 6.4 months (95% CI,
      6.2 to 8.3) in the pembrolizumab-combination group and 4.8 months (95% CI, 4.3 to
      5.7) in the placebo-combination group (hazard ratio for disease progression or
      death, 0.56; 95% CI, 0.45 to 0.70; P<0.001). Adverse events of grade 3 or higher
      occurred in 69.8% of the patients in the pembrolizumab-combination group and in
      68.2% of the patients in the placebo-combination group. Discontinuation of
      treatment because of adverse events was more frequent in the pembrolizumab
      combination group than in the placebo-combination group (13.3% vs. 6.4%).
      CONCLUSIONS: In patients with previously untreated metastatic, squamous NSCLC,
      the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or
      nab-paclitaxel resulted in significantly longer overall survival and progression
      free survival than chemotherapy alone. (Funded by Merck Sharp & Dohme; KEYNOTE
      407 ClinicalTrials.gov number, NCT02775435 .).

PMID- 30280642
TI  - Acute neuropathic pain and the transition to chronic postsurgical pain.

PMID- 30280641
TI  - First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung
      Cancer.
AB  - BACKGROUND: Enhancing tumor-specific T-cell immunity by inhibiting programmed
      death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in
      the treatment of extensive-stage small-cell lung cancer. Combining checkpoint
      inhibition with cytotoxic chemotherapy may have a synergistic effect and improve
      efficacy. METHODS: We conducted this double-blind, placebo-controlled, phase 3
      trial to evaluate atezolizumab plus carboplatin and etoposide in patients with
      extensive-stage small-cell lung cancer who had not previously received treatment.
      Patients were randomly assigned in a 1:1 ratio to receive carboplatin and
      etoposide with either atezolizumab or placebo for four 21-day cycles (induction
      phase), followed by a maintenance phase during which they received either
      atezolizumab or placebo (according to the previous random assignment) until they
      had unacceptable toxic effects, disease progression according to Response
      Evaluation Criteria in Solid Tumors, version 1.1, or no additional clinical
      benefit. The two primary end points were investigator-assessed progression-free
      survival and overall survival in the intention-to-treat population. RESULTS: A
      total of 201 patients were randomly assigned to the atezolizumab group, and 202
      patients to the placebo group. At a median follow-up of 13.9 months, the median
      overall survival was 12.3 months in the atezolizumab group and 10.3 months in the
      placebo group (hazard ratio for death, 0.70; 95% confidence interval [CI], 0.54
      to 0.91; P=0.007). The median progression-free survival was 5.2 months and 4.3
      months, respectively (hazard ratio for disease progression or death, 0.77; 95%
      CI, 0.62 to 0.96; P=0.02). The safety profile of atezolizumab plus carboplatin
      and etoposide was consistent with the previously reported safety profile of the
      individual agents, with no new findings observed. CONCLUSIONS: The addition of
      atezolizumab to chemotherapy in the first-line treatment of extensive-stage small
      cell lung cancer resulted in significantly longer overall survival and
      progression-free survival than chemotherapy alone. (Funded by F. Hoffmann-La
      Roche/Genentech; IMpower133 ClinicalTrials.gov number, NCT02763579 .).

PMID- 30280643
TI  - A subject-specific integrative biomechanical framework of the pelvis for gait
      analysis.
AB  - Analysis of the human locomotor system using rigid-body musculoskeletal models
      has increased in the biomechanical community with the objective of studying
      muscle activations of different movements. Simultaneously, the finite element
      method has emerged as a complementary approach for analyzing the mechanical
      behavior of tissues. This study presents an integrative biomechanical framework
      for gait analysis by linking a musculoskeletal model and a subject-specific
      finite element model of the pelvis. To investigate its performance, a convergence
      study was performed and its sensitivity to the use of non-subject-specific
      material properties was studied. The total hip joint force estimated by the rigid
      musculoskeletal model and by the finite element model showed good agreement,
      suggesting that the integrative approach estimates adequately (in shape and
      magnitude) the hip total contact force. Previous studies found movements of up to
      1.4 mm in the anterior-posterior direction, for single leg stance. These results
      are comparable with the displacement values found in this study: 0-0.5 mm in the
      sagittal axis. Maximum von Mises stress values of approximately 17 MPa were found
      in the pelvic bone. Comparing this results with a previous study of our group,
      the new findings show that the introduction of muscular boundary conditions and
      the flexion-extension movement of the hip reduce the regions of high stress and
      distributes more uniformly the stress across the pelvic bone. Thus, it is thought
      that muscle force has a relevant impact in reducing stresses in pelvic bone
      during walking of the finite element model proposed in this study. Future work
      will focus on including other deformable structures, such as the femur and the
      tibia, and subject-specific material properties.

PMID- 30280644
TI  - Fumonisin occurrence in wheat-based products from Argentina.
AB  - In Argentina, wheat is the most consumed cereal by the human population. Since
      fumonisins occurence in wheat grains and wheat-based products have been reported
      worldwide, a survey was conducted in order to determine fumonisin contamination
      in 91 wheat-based products (white wheat flour samples, wheat flour used at bakery
      products and whole-wheat flour samples) collected from different retail stores of
      Rio Cuarto city in Argentina using HPLC-MS/MS. Sixty-seven samples (74%) showed
      contamination by fumonisins. From these samples, 16 showed fumonisin levels
      between LOD and LOQ (between 0.01 to 0.05 ng/g), while fumonisins (FB1 + FB2) in
      quantifiable samples ranged from 0.05 ng/g to 18.9 ng/g. Although FB1 was more
      prevalent, FB2 was foun3d in higher levels than FB1. Overall, fumonisin
      prevalence was high, but concentrations were far below EU or USA limits set for
      maize and maize-based products.

PMID- 30280645
TI  - Comparison of conventional methods of simultaneous intrusion and retraction of
      maxillary anterior: a finite element analysis.
AB  - OBJECTIVE: To study the biomechanical effects of the three-piece intrusion arch
      and Kalra simultaneous intrusion and retraction arch (K-SIR) on simultaneous
      intrusion and retraction of maxillary anterior teeth. DESIGN: Three-dimensional
      analysis of stresses and displacement of the anterior and posterior teeth with
      the three-piece intrusion arch and K-SIR arch was done using the finite element
      method (FEM). SETTING: Department of Orthodontics, Surendera Dental College and
      Research Institute, India. MATERIAL AND METHODS: For this investigation, the
      geometric model of the maxilla was constructed using a computed tomography scan.
      0.022 * 0.028-inch MBT brackets and molar tubes were modelled, with the specified
      tip and torque values for all maxillary teeth. The wire components for the three
      piece intrusion arch and K-SIR arch were modelled initially as a line diagram and
      then converted to three dimensional models. The material characteristics which
      include the Young's modulus and Poisson's ratio were assigned. After defining the
      boundary conditions, force systems were applied as per design. The analysis was
      carried out using ANSYS Version 12.1 software. The von Mises stress, principal
      stress on PDL and alveolar bone, change in the inclination of incisors and
      initial displacement of the teeth in bucco-palatal, mesio- distal and vertical
      direction were analysed. RESULTS: Stresses in cortical bone were greater than
      cancellous. Both modalities showed intrusion of the anterior teeth, although this
      was slightly more in the three- piece intrusion arch. On studying the principal
      stresses in the PDL, the three-piece intrusion arch displayed uniform stress
      distribution compared to K-SIR arch. CONCLUSION: The FEM cannot reflect actual
      biological responses within the human body to orthodontic forces but based on
      these findings, the three-piece intrusion arch showed better stress distribution
      and controlled tooth movement than the K-SIR arch.

PMID- 30280647
TI  - Comparison of cross-matching method for detection of DEA 7 blood incompatibility.
AB  - We compared 3 major cross-match (XM) tests to identify dog erythrocyte antigen
      (DEA) 7 blood incompatibilities in dogs as a result of anti-DEA 7 antibodies: gel
      (GEL), standard tube (TUBE) agglutination, and immunochromatography strips
      (STRIP). Blood samples from 42 dogs were typed for DEA 7; 2 tested DEA 7-positive
      (DEA 7+). The 40 DEA 7-negative (DEA 7-) plasma samples were cross-matched
      against the 2 DEA 7+ and 3 DEA 7- red blood cell (RBC) samples by GEL to identify
      samples with anti-DEA 7 antibodies. Twenty DEA 7- plasma samples without and with
      anti-DEA 7 antibodies were cross-matched with samples of the 2 DEA 7+ RBCs in a
      double-blind fashion using the TUBE and STRIP XM methods. GEL results were used
      as the reference method for comparison. To determine relationships between
      results, 2 * 2 tables were used. Cohen kappa coefficient (kappa) was calculated
      between results of GEL and the other 2 methods. With GEL, 21 of 40 XM tests were
      positive and 19 of 40 negative for anti-DEA 7 antibodies. The same results were
      obtained by TUBE, whereas only 1 of 40 XM tests was positive by STRIP. There was
      a statistically significant relationship between results of GEL and TUBE ( p <
      0.000) with perfect agreement (kappa = 1.000), but not between GEL and STRIP
      results ( p = 1.000) in which agreement was equivalent to chance (kappa =
      0.0453). The GEL and TUBE XM tests, but not STRIP, are useful methods for
      identification of DEA 7 incompatibilities caused by anti-DEA 7 antibodies.

PMID- 30280648
TI  - Drug-Coated Balloon Treatment of Femoropopliteal Lesions Typically Excluded From
      Clinical Trials: 12-Month Findings From the IN.PACT Global Study.
AB  - PURPOSE: To report a post hoc analysis comparing outcomes between subjects who
      would have been included in the IN.PACT SFA randomized controlled trial vs those
      who would have been excluded. METHODS: The 1406 subjects enrolled in the IN.PACT
      Global Study ( ClinicalTrials.gov identifier NCT01609296) were retrospectively
      assigned to a standard-use group (n=281) based on the inclusion and exclusion
      criteria from the randomized IN.PACT SFA trial; the remaining 1125 patients were
      assigned to the broader-use group. Freedom from clinically-driven target lesion
      revascularization (CD-TLR) was evaluated at 12 months. The composite primary
      safety endpoint was freedom from 30-day device- and procedure-related death plus
      freedom from 12-month target limb major amputation and clinically-driven target
      vessel revascularization (CD-TVR). Functional outcomes were evaluated with
      dedicated questionnaires. RESULTS: Compared with the standard-use cohort, the
      broader-use lesions were longer, more calcified, and had more popliteal
      involvement, bilateral disease, and in-stent restenosis (p<0.001 for all).
      Freedom from 12-month CD-TLR by Kaplan-Meier analysis was 96.6% for the standard
      use group and 91.6% for the broader-use group (p=0.005). The safety endpoint was
      96.2% in the standard-use group and 91.0% in the broader-use group (p=0.003). The
      12-month CD-TLR (3.4% standard-use vs 8.5% broader-use, p=0.004) and CD-TVR (4.2%
      standard-use vs 9.1% broader-use, p=0.008) were increased in the broader-use
      group. Twelve-month all-cause mortality was not increased (3.8% standard-use vs
      3.4% broader-use, p=0.852). CONCLUSION: Post hoc analysis of the IN.PACT Global
      Study of real-world patients demonstrated consistent outcomes with significant
      clinical improvement to 12 months in subjects with complex lesions typically
      excluded from a randomized controlled trial.

PMID- 30280646
TI  - Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing.
AB  - BACKGROUND: The World Health Organization recommends drug-susceptibility testing
      of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide
      treatment decisions and improve outcomes. Whether DNA sequencing can be used to
      accurately predict profiles of susceptibility to first-line antituberculosis
      drugs has not been clear. METHODS: We obtained whole-genome sequences and
      associated phenotypes of resistance or susceptibility to the first-line
      antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for
      isolates from 16 countries across six continents. For each isolate, mutations
      associated with drug resistance and drug susceptibility were identified across
      nine genes, and individual phenotypes were predicted unless mutations of unknown
      association were also present. To identify how whole-genome sequencing might
      direct first-line drug therapy, complete susceptibility profiles were predicted.
      These profiles were predicted to be susceptible to all four drugs (i.e.,
      pansusceptible) if they were predicted to be susceptible to isoniazid and to the
      other drugs or if they contained mutations of unknown association in genes that
      affect susceptibility to the other drugs. We simulated the way in which the
      negative predictive value changed with the prevalence of drug resistance.
      RESULTS: A total of 10,209 isolates were analyzed. The largest proportion of
      phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest
      was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid,
      rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%,
      94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was
      correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516
      isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had
      complete genotypic predictions, among which 5250 profiles (89.5%) were correctly
      predicted. Among the 4037 phenotypic profiles that were predicted to be
      pansusceptible, 3952 (97.9%) were correctly predicted. CONCLUSIONS: Genotypic
      predictions of the susceptibility of M. tuberculosis to first-line drugs were
      found to be correlated with phenotypic susceptibility to these drugs. (Funded by
      the Bill and Melinda Gates Foundation and others.).

PMID- 30280649
TI  - Global Post-Market Clinical Follow-up of the Treovance Stent-Graft for
      Endovascular Aneurysm Repair: One-Year Results From the RATIONALE Registry.
AB  - PURPOSE:: To evaluate the safety and performance of the Treovance stent-graft.
      METHODS:: The global, multicenter RATIONALE registry ( ClinicalTrials.gov;
      identifier NCT03449875) prospectively enrolled 202 patients (mean age 73.0+/-7.8
      years; 187 men) with abdominal aortic aneurysms (AAA) suitable for endovascular
      aneurysm repair (EVAR) using the Treovance. The composite primary safety endpoint
      was site-reported all-cause mortality and major morbidity. The primary efficacy
      outcome was clinical success. Further outcomes evaluated included technical
      success; stent-graft migration, patency, and integrity; endoleak; and aneurysm
      size changes. RESULTS:: Technical success was 96% (194/202); 8 patients had
      unresolved type I endoleaks at the end of the procedure. There was no 30-day
      mortality and 1% major morbidity (1 myocardial infarction and 1 bowel ischemia).
      Clinical success at 1 year was confirmed in 194 (96%) patients; 6 of 8 patients
      had new/persistent endoleaks and 2 had aneurysm expansion without identified
      endoleak. A total of 8 (4%) reinterventions were required during the mean 13.7+/
      3.1 months of follow-up (median 12.8). At 1 year, the Kaplan-Meier estimate for
      freedom from reintervention was 95.6% (95% CI 91.4% to 97.8%). Other estimates
      were 95.5% (95% CI 91.7% to 97.6%) for freedom from endoleak type I/III and 97.4%
      (95% CI 94.2% to 98.9%) for freedom from aneurysm expansion. Thirteen (6.4%)
      patients died; no death was aneurysm related. CONCLUSION:: The RATIONALE registry
      showed favorable safety and clinical performance of the Treovance stent-graft for
      the treatment of infrarenal AAAs in a real-world setting.

PMID- 30280650
TI  - Rapid differentiation of Staphylococcus aureus subspecies based on MALDI-TOF MS
      profiles.
AB  - Staphylococcus aureus encompasses 2 subspecies ( aureus and anaerobius) with
      significant differences in their epidemiology and pathogenicity. We evaluated the
      suitability of matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) for the rapid identification of both subspecies using
      a panel of 52 S. aureus isolates (30 subsp. anaerobius and 22 subsp. aureus)
      recovered from different origins, countries, and years. The on-board library
      identification system correctly identified 42 of 52 (81%) S. aureus isolates at
      the species level with score values >2.0. Limited performance was observed for
      differentiation of S. aureus subspecies (particularly subsp. anaerobius). Visual
      inspection of MALDI-TOF MS profiles identified 5 subspecies-specific mass peaks (
      m/ z 3430 and 6861 in S. aureus subsp. anaerobius, and m/ z 4046, 6890, and 8093
      in S. aureus subsp. aureus) with 100% sensitivity and specificity values, which
      is potentially useful for differentiating these subspecies. The suitability of 3
      models, Genetic Analysis (GA), Quick Classifier (QC), and Supervised Neural
      Network, for automatic identification of both subspecies was evaluated using the
      Recognition Capability (RC) and Cross Validation (CV) values provided by the on
      board ClinProTools software. The GA and QC models reached RC and CV values of
      100%. Both models were externally validated using a panel of 26 S. aureus
      isolates of both subspecies, with both models correctly classifying all isolates
      of both subspecies. MALDI-TOF MS coupled with ClinProTools software represents a
      rapid and simple approach for S. aureus subspecies discrimination.

PMID- 30280652
TI  - Externally triggered patient-controlled local anesthesia.

PMID- 30280653
TI  - Blood-Brain Barrier: From Physiology to Disease and Back.
AB  - The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells,
      and pathogens from entering the brain. At the same time, the BBB regulates
      transport of molecules into and out of the central nervous system (CNS), which
      maintains tightly controlled chemical composition of the neuronal milieu that is
      required for proper neuronal functioning. In this review, we first examine
      molecular and cellular mechanisms underlying the establishment of the BBB. Then,
      we focus on BBB transport physiology, endothelial and pericyte transporters, and
      perivascular and paravascular transport. Next, we discuss rare human monogenic
      neurological disorders with the primary genetic defect in BBB-associated cells
      demonstrating the link between BBB breakdown and neurodegeneration. Then, we
      review the effects of genes underlying inheritance and/or increased
      susceptibility for Alzheimer's disease (AD), Parkinson's disease (PD),
      Huntington's disease, and amyotrophic lateral sclerosis (ALS) on BBB in relation
      to other pathologies and neurological deficits. We next examine how BBB
      dysfunction relates to neurological deficits and other pathologies in the
      majority of sporadic AD, PD, and ALS cases, multiple sclerosis, other
      neurodegenerative disorders, and acute CNS disorders such as stroke, traumatic
      brain injury, spinal cord injury, and epilepsy. Lastly, we discuss BBB-based
      therapeutic opportunities. We conclude with lessons learned and future
      directions, with emphasis on technological advances to investigate the BBB
      functions in the living human brain, and at the molecular and cellular level, and
      address key unanswered questions.

PMID- 30280651
TI  - Phase 2b Controlled Trial of M72/AS01E Vaccine to Prevent Tuberculosis.
AB  - BACKGROUND: A vaccine to interrupt the transmission of tuberculosis is needed.
      METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2b
      trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia.
      Human immunodeficiency virus (HIV)-negative adults 18 to 50 years of age with
      latent M. tuberculosis infection (by interferon-gamma release assay) were
      randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or
      placebo intramuscularly 1 month apart. Most participants had previously received
      the bacille Calmette-Guerin vaccine. We assessed the safety of M72/AS01E and its
      efficacy against progression to bacteriologically confirmed active pulmonary
      tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with
      sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or
      both. RESULTS: We report the primary analysis (conducted after a mean of 2.3
      years of follow-up) of the ongoing trial. A total of 1786 participants received
      M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the
      respective groups were included in the according-to-protocol efficacy cohort. A
      total of 10 participants in the M72/AS01E group met the primary case definition
      (bacteriologically confirmed active pulmonary tuberculosis, with confirmation
      before treatment), as compared with 22 participants in the placebo group
      (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy
      was 54.0% (90% confidence interval [CI], 13.9 to 75.4; 95% CI, 2.9 to 78.2;
      P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine
      efficacy, 57.0%; 90% CI, 19.9 to 76.9; 95% CI, 9.7 to 79.5; P=0.03). There were
      more unsolicited reports of adverse events in the M72/AS01E group (67.4%) than in
      the placebo group (45.4%) within 30 days after injection, with the difference
      attributed mainly to injection-site reactions and influenza-like symptoms.
      Serious adverse events, potential immune-mediated diseases, and deaths occurred
      with similar frequencies in the two groups. CONCLUSIONS: M72/AS01E provided 54.0%
      protection for M. tuberculosis-infected adults against active pulmonary
      tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline
      Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598 .).

PMID- 30280656
TI  - [EXPRESS] CD11b activated Src signal attenuates neuroinflammatory pain by
      orchestrating inflammatory and anti-inflammatory cytokines in microglia.
AB  - Neuroinflammation plays an important role in the induction and maintenance of
      chronic pain. Orchestra of pattern-recognition receptors (PRRs) induced pro
      inflammatory and anti-inflammatory cytokines are critical for inflammation
      homeostasis. CD11b on macrophages could inhibit toll like receptor (TLR)
      activation induced inflammatory responses. However, the function of CD11b on
      microglia remains unknown. In the current study, we demonstrated that CD11b
      deficient microglia cells produced more inflammatory cytokines such as IL-6 and
      TNF-alpha, while less anti-inflammatory cytokines. Signal transduction assay
      confirmed that NF-kappaB activation was increased in CD11b deficient microglia
      cells, which was resulted from decreased activation of Src. Inhibition of Src by
      PP1 increased inflammation in wildtype microglia cells significantly, but not in
      CD11b deficient microglia cells. In vivo, CD11b deficient mice were more
      susceptible to CCI induced allodynia and hyperalgesia with significantly more
      inflammatory cytokines expression. All these results indicated that the
      regulatory function of CD11b-Src signal pathway on both inflammatory and anti
      inflammatory cytokines in microglia cells, which is a potential target in
      neuropathic pain treatment.

PMID- 30280655
TI  - An Outbreak of Synthetic Cannabinoid-Associated Coagulopathy in Illinois.
AB  - BACKGROUND: In March and April 2018, more than 150 patients presented to
      hospitals in Illinois with coagulopathy and bleeding diathesis. Area physicians
      and public health organizations identified an association between coagulopathy
      and synthetic cannabinoid use. Preliminary tests of patient serum samples and
      drug samples revealed that brodifacoum, an anticoagulant, was the likely
      adulterant. METHODS: We reviewed physician-reported data from patients admitted
      to Saint Francis Medical Center in Peoria, Illinois, between March 28 and April
      21, 2018, and included in a case series adult patients who met the criteria used
      to diagnose synthetic cannabinoid-associated coagulopathy. A confirmatory
      anticoagulant poisoning panel was ordered at the discretion of the treating
      physician. RESULTS: A total of 34 patients were identified as having synthetic
      cannabinoid-associated coagulopathy during 45 hospitalizations. Confirmatory
      anticoagulant testing was performed in 15 of the 34 patients, and superwarfarin
      poisoning was confirmed in the 15 patients tested. Anticoagulant tests were
      positive for brodifacoum in 15 patients (100%), difenacoum in 5 (33%),
      bromadiolone in 2 (13%), and warfarin in 1 (7%). Common symptoms at presentation
      included gross hematuria in 19 patients (56%) and abdominal pain in 16 (47%).
      Computed tomography was performed to evaluate abdominal pain and revealed renal
      abnormalities in 12 patients. Vitamin K1 (phytonadione) was administered orally
      in all 34 patients and was also administered intravenously in 23 (68%). Red-cell
      transfusion was performed in 5 patients (15%), and fresh-frozen plasma infusion
      in 19 (56%). Four-factor prothrombin complex concentrate was used in 1 patient.
      One patient died from complications of spontaneous intracranial hemorrhage.
      CONCLUSIONS: Our data indicate that superwarfarin adulterants of synthetic
      cannabinoids can lead to clinically significant coagulopathy. In our series, in
      most of the cases in which the patient presented with bleeding diathesis,
      symptoms were controlled with the use of vitamin K1 replacement therapy. The
      specific synthetic cannabinoid compounds are not known.

PMID- 30280657
TI  - Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer.
AB  - BACKGROUND: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK)
      inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung
      cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as
      compared with crizotinib, in patients with advanced ALK-positive NSCLC who have
      not previously received an ALK inhibitor is unclear. METHODS: In an open-label,
      phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK
      positive NSCLC who had not previously received ALK inhibitors to receive
      brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg)
      or crizotinib at a dose of 250 mg twice daily. The primary end point was
      progression-free survival as assessed by blinded independent central review.
      Secondary end points included the objective response rate and intracranial
      response. The first interim analysis was planned when approximately 50% of 198
      expected events of disease progression or death had occurred. RESULTS: A total of
      275 patients underwent randomization; 137 were assigned to brigatinib and 138 to
      crizotinib. At the first interim analysis (99 events), the median follow-up was
      11.0 months in the brigatinib group and 9.3 months in the crizotinib group. The
      rate of progression-free survival was higher with brigatinib than with crizotinib
      (estimated 12-month progression-free survival, 67% [95% confidence interval {CI},
      56 to 75] vs. 43% [95% CI, 32 to 53]; hazard ratio for disease progression or
      death, 0.49 [95% CI, 0.33 to 0.74]; P<0.001 by the log-rank test). The confirmed
      objective response rate was 71% (95% CI, 62 to 78) with brigatinib and 60% (95%
      CI, 51 to 68) with crizotinib; the confirmed rate of intracranial response among
      patients with measurable lesions was 78% (95% CI, 52 to 94) and 29% (95% CI, 11
      to 52), respectively. No new safety concerns were noted. CONCLUSIONS: Among
      patients with ALK-positive NSCLC who had not previously received an ALK
      inhibitor, progression-free survival was significantly longer among patients who
      received brigatinib than among those who received crizotinib. (Funded by Ariad
      Pharmaceuticals; ALTA-1L ClinicalTrials.gov number, NCT02737501 .).

PMID- 30280659
TI  - New Mechanisms of GI Ulceration & Healing: Physiology, Pharmacology & Pathology.

PMID- 30280654
TI  - Wearable Cardioverter-Defibrillator after Myocardial Infarction.
AB  - BACKGROUND: Despite the high rate of sudden death after myocardial infarction
      among patients with a low ejection fraction, implantable cardioverter
      defibrillators are contraindicated until 40 to 90 days after myocardial
      infarction. Whether a wearable cardioverter-defibrillator would reduce the
      incidence of sudden death during this high-risk period is unclear. METHODS: We
      randomly assigned (in a 2:1 ratio) patients with acute myocardial infarction and
      an ejection fraction of 35% or less to receive a wearable cardioverter
      defibrillator plus guideline-directed therapy (the device group) or to receive
      only guideline-directed therapy (the control group). The primary outcome was the
      composite of sudden death or death from ventricular tachyarrhythmia at 90 days
      (arrhythmic death). Secondary outcomes included death from any cause and
      nonarrhythmic death. RESULTS: Of 2302 participants, 1524 were randomly assigned
      to the device group and 778 to the control group. Participants in the device
      group wore the device for a median of 18.0 hours per day (interquartile range,
      3.8 to 22.7). Arrhythmic death occurred in 1.6% of the participants in the device
      group and in 2.4% of those in the control group (relative risk, 0.67; 95%
      confidence interval [CI], 0.37 to 1.21; P=0.18). Death from any cause occurred in
      3.1% of the participants in the device group and in 4.9% of those in the control
      group (relative risk, 0.64; 95% CI, 0.43 to 0.98; uncorrected P=0.04), and
      nonarrhythmic death in 1.4% and 2.2%, respectively (relative risk, 0.63; 95% CI,
      0.33 to 1.19; uncorrected P=0.15). Of the 48 participants in the device group who
      died, 12 were wearing the device at the time of death. A total of 20 participants
      in the device group (1.3%) received an appropriate shock, and 9 (0.6%) received
      an inappropriate shock. CONCLUSIONS: Among patients with a recent myocardial
      infarction and an ejection fraction of 35% or less, the wearable cardioverter
      defibrillator did not lead to a significantly lower rate of the primary outcome
      of arrhythmic death than control. (Funded by the National Institutes of Health
      and Zoll Medical; VEST ClinicalTrials.gov number, NCT01446965 .).

PMID- 30280660
TI  - Activation of the glutathione peroxidase by metformin in the bile-duct ligation
      induced liver injury: in vivo combined with molecular docking studies.
AB  - Inhibition of hepatic fibrosis is an attainable objective in managing the chronic
      liver disease. The present study aimed to investigate possible defensive effects
      of metformin on activities of antioxidant enzymes, hydroxyproline content, and
      biochemical factors in bile duct ligation (BDL)-induced cholestatic rats. The
      interactive behavior of metformin with glutathione peroxidase (GPx) enzyme was
      also explained by molecular docking and conformation characterization. The
      present study was conducted on 28-adult male Wistar rats classified into four 7
      animal groups: sham-control, mere BDL, and BDL+ metformin received daily
      metformin as gavage in two doses 250 and 500 mg/kg bw for 10 days. Biochemical
      analysis, hydroxyproline content, and antioxidant enzymes activity were also
      determined. The hydroxyproline content significantly increased, but the GPx
      enzyme activity significantly decreased in the hepatic tissue following BDL
      indicating that an oxidative stress-related model in rats was successfully
      constituted. Administration of metformin at two doses attenuated hydroxyproline
      content in the cholestatic liver and ameliorated the depletion of GPx enzyme
      activities compared to a non-treated BDL group (P-value <= 0.05). Molecular
      docking study provides the evidence for metformin ability to regulate enzymatic
      activity of GPx. The research data indicated that due to novel hepatoprotective
      effects of metformin in an animal model with BDL-induced liver injury, it was a
      potential beneficial therapeutic agent for treating the cholestatic liver
      disease. The main mechanism might contribute to antioxidant actions particularly
      via GPx enzyme.

PMID- 30280658
TI  - Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC.
AB  - BACKGROUND: An earlier analysis in this phase 3 trial showed that durvalumab
      significantly prolonged progression-free survival, as compared with placebo,
      among patients with stage III, unresectable non-small-cell lung cancer (NSCLC)
      who did not have disease progression after concurrent chemoradiotherapy. Here we
      report the results for the second primary end point of overall survival. METHODS:
      We randomly assigned patients, in a 2:1 ratio, to receive durvalumab
      intravenously, at a dose of 10 mg per kilogram of body weight, or matching
      placebo every 2 weeks for up to 12 months. Randomization occurred 1 to 42 days
      after the patients had received chemoradiotherapy and was stratified according to
      age, sex, and smoking history. The primary end points were progression-free
      survival (as assessed by blinded independent central review) and overall
      survival. Secondary end points included the time to death or distant metastasis,
      the time to second progression, and safety. RESULTS: Of the 713 patients who
      underwent randomization, 709 received the assigned intervention (473 patients
      received durvalumab and 236 received placebo). As of March 22, 2018, the median
      follow-up was 25.2 months. The 24-month overall survival rate was 66.3% (95%
      confidence interval [CI], 61.7 to 70.4) in the durvalumab group, as compared with
      55.6% (95% CI, 48.9 to 61.8) in the placebo group (two-sided P=0.005). Durvalumab
      significantly prolonged overall survival, as compared with placebo (stratified
      hazard ratio for death, 0.68; 99.73% CI, 0.47 to 0.997; P=0.0025). Updated
      analyses regarding progression-free survival were similar to those previously
      reported, with a median duration of 17.2 months in the durvalumab group and 5.6
      months in the placebo group (stratified hazard ratio for disease progression or
      death, 0.51; 95% CI, 0.41 to 0.63). The median time to death or distant
      metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo
      group (stratified hazard ratio, 0.53; 95% CI, 0.41 to 0.68). A total of 30.5% of
      the patients in the durvalumab group and 26.1% of those in the placebo group had
      grade 3 or 4 adverse events of any cause; 15.4% and 9.8% of the patients,
      respectively, discontinued the trial regimen because of adverse events.
      CONCLUSIONS: Durvalumab therapy resulted in significantly longer overall survival
      than placebo. No new safety signals were identified. (Funded by AstraZeneca;
      PACIFIC ClinicalTrials.gov number, NCT02125461 .).

PMID- 30280662
TI  - Pharmacological Effects Of Carvacrol In Vitro Studies: A Review.
AB  - : During early development of a drug, in vivo studies precede or complement
      pharmacological bioassays in laboratory animals (in vivo studies). Carvacrol is a
      product with high therapeutic potential, which in vitro studies have been showing
      favorable results in different cellular models or methodological designs.
      Therefore, the objective was to conduct a systematic review to analyze
      pharmacological effects of carvacrol in in vitro studies. A comprehensive
      literature research using Science Direct, Scopus, MEDLINE-PubMed, Web of Science.
      SELECTION CRITERIA: Four databases were used (Internet sources), such as:
      National Library of Medicine (MEDLINE-PubMed), Science Direct, Web of Science and
      Scopus, using different combinations of the following keywords: carvacrol, drug
      therapy, therapeutic uses, in vitro study. The searches on databases were for
      studies conducted in the period up to and including September 2016. A total of
      3,269 studies were initially identified, with only 31 meeting the inclusion
      criteria. The included studies showed a variety of in vitro models able to
      determine the properties of Carvacrol. Many mechanisms of action of Carvacrol
      were noted: antimicrobial effect (7 studies), bactericidal (4), bactericidal and
      antifungal (1), anti-inflammatory (4), anticancer (4), mutagenic activity (4),
      antioxidant (3), antifungal (3), antidepressant (1), modulator of nerve impulses
      (1) and immunological modulator (1). The In vitro studies with Carvacrol included
      in this review showed a diversity of models and confirmed the therapeutic
      potential of this product in relation to several diseases.

PMID- 30280661
TI  - Nutraceutical-based integrative medicine: Adopting a Mediterranean diet pyramid
      for attaining healthy ageing in veterans with disabilities.
AB  - Veterans with disability represent a big burden worldwide and often require long
      term rehabilitation. Unhealthy dietary and lifestyle habits, including smoke and
      alcohol abuse, are common in veterans. In the context of integrative medicine
      approaches, the "complementary and alternative medicine" has been suggested for
      the management of chronic diseases. However, the potential risk of interaction
      between herbal products, dietary supplements and drugs must be considered in
      veterans. The Mediterranean diet has been suggested as a natural, non
      pharmacological nutraceutical for healthy ageing. Although there is a broad
      consensus on the positive effect of plant foods consumption, the presence of
      glucosinolates, flavonoids and furanocoumarins in some plant foods and beverages
      must be taken into consideration owing to their potential interfering with drugs
      metabolism and bioavailability. Albeit seasonality could ensure the maintenance
      of the single dose of phytochemical below that at which adverse effects in some
      individuals genetically predisposed or unpleasant drug interactions in diseased
      subjects can occur, a personalized nutrition is recommended in veterans who are
      in treatment for comorbidities. Furthermore, sports practice can lead veterans
      with motor disabilities and mental impairments to excel in some disciplines,
      giving rise to the phenomenon of the Paralympics and the development of
      "recreational therapy". Moreover, outdoor lifestyle, through vitamin D synthesis,
      and conviviality, improving socialization, could account for the Mediterranean
      lifestyle health benefits. In this work we propose for veterans a Mediterranean
      Pyramid, which could be the basis for integrative medicine for veterans with
      disabilities, patient-centered approaches and interprofessional (including
      physical medicine and rehabilitation clinicians, pharmacists and nutritionists)
      interventions.

PMID- 30280663
TI  - Drug-drug interactions of P-gp substrates unrelated to CYP metabolism.
AB  - Background: Recent US Food and Drug Administration (FDA) draft guidance on
      pharmacokinetic drug-drug interactions (DDIs) has highlighted the clinical
      importance of ABC transporters B1 or P-glycoprotein (P-gp), hepatic organic anion
      transporting polypeptide transporters and breast cancer resistant protein because
      of their broad substrate specificity and the potential to be involved in DDIs.
      This guidance has indicated that digoxin, dabigatran etexilate and fexofenadine
      are P-gp substrate drugs and has defined P-gp inhibitors as those that increase
      the AUC of digoxin by ?1.25-fold in clinical DDI studies. However, when substrate
      drugs of both CYPs and P-gp are involved in DDIs, it remains that the mechanisms
      of DDIs will be quite ambiguous in assessing how much the CYPs and/or drug
      transporters partially contribute to DDIs. Objective: Since there are no detailed
      manuscripts that summarizes P-gp interactions unrelated to CYP metabolism, this
      article reviews the effects of potent P-gp inhibitors and P-gp inducers on the
      pharmacokinetics of P-gp substrate drugs, including digoxin, talinolol,
      dabigatran etexilate, and fexofenadine in human studies. In addition, the present
      outcome were to determine the PK changes caused by DDIs among P-gp substrate
      drugs without CYP metabolism in human DDI studies. Conclusion: Our manuscript
      concludes that the PK changes of the DDIs among P-gp drugs unrelated to CYP
      metabolism are less likely to be serious, and it appears to be convincing that
      the absences of clinical effects caused to the PK changes by the P-gp inducers is
      predominant compared with the excessive effects caused to those by the P-gp
      inhibitors.

PMID- 30280664
TI  - Survey of Drug Oxidation Activities in Liver and Intestine Microsomes of
      Individual Common Marmosets, a New Nonhuman Primate Animal Model.
AB  - BACKGROUND: Common marmosets (Callithrix jacchus) are potentially useful nonhuman
      primate models for preclinical studies. Information for major drug-metabolizing
      cytochrome P450 (P450) enzymes is now available that supports the use of this
      primate species as an animal model for drug development. Here, we collect and
      provide an overview of information on the activities of common marmoset liver and
      intestine microsomes with respect to 28 typical human P450 probe oxidations.
      RESULTS: Marmoset P450 2D6/8-dependent R-metoprolol O-demethylation activities in
      liver microsomes were significantly correlated with those of midazolam 1'- and 4
      hydroxylations, testosterone 6beta-hydroxylation, and progesterone 6beta
      hydroxylation, which are probe reactions for marmoset P450 3A4/5/90. In
      marmosets, the oxidation activities of liver microsomes and intestine microsomes
      were roughly comparable for midazolam and terfenadine. Overall, multiple forms of
      marmoset P450 enzymes in livers and intestines had generally similar substrate
      recognition functionalities to those of human and/or cynomolgus monkey P450
      enzymes. CONCLUSION: The marmoset could be a model animal for humans with respect
      to the first-pass extraction of terfenadine and related substrates. These
      findings provide a foundation for understanding individual pharmacokinetic and
      toxicological results in nonhuman primates as preclinical models and will help to
      further support understanding of the molecular mechanisms of human P450 function.

PMID- 30280665
TI  - Nanomedicine for gene delivery for the treatment of cardiovascular diseases.
AB  - Myocardial infarction (MI) is the most severe ischemic heart disease and directly
      leads to heart failure till death. Target molecules have been identified in the
      event of MI including increasing angiogenesis, promoting cardiomyocyte survival,
      improving heart function and restraining inflammation and myocyte activation and
      subsequent fibrosis. All of which are substantial in cardiomyocyte protection and
      preservation of cardiac function. To modulate target molecule expression, virus
      and non-virus-mediated gene transfer have been investigated. Despite successful
      in animal models of MI, virus-mediated gene transfer is hampered by poor
      targeting efficiency, low packaging capacity for large DNA sequences,
      immunogenicity induced by virus and random integration into human genome.
      Nanoparticles could be synthesized and equipped on purpose for large scale
      production. They are relatively small in size and do not incorporate into genome.
      They could carry DNA and drug within the same transfer. All of these properties
      make them an alternative strategy for gene transfer. In the review, we first
      introduce the pathological progression of MI. After concise discussion the
      current status of virus-mediated gene therapy in treating MI, we overview the
      history and development of nanoparticle-based gene delivery system. We point out
      the limitations and future perspective in the field of nanoparticle vehicle.
      Ultimately, we hope that this review could help to better understand how far we
      are with nanoparticle-facilitated gene transfer strategy and what obstacles we
      need to solve for utilization of nanomedicine in the treatment of MI.

PMID- 30280666
TI  - Stroke as a Cause of Death in Death Certificates of Patients with Dementia: A
      Cohort Study from the Swedish Dementia Registry.
AB  - INTRODUCTION: Patients with dementia may be at a higher risk for death from
      stroke. We aimed to describe characteristics of dementia patients that died from
      ischemic stroke (IS) in Sweden. METHODS: A retrospective longitudinal analysis of
      prospectively collected data of patients registered into the Swedish Dementia
      Registry was conducted. Data on causes of death, drugs and comorbidities were
      acquired from the Swedish nationwide health registers. Deaths were attributed to
      stroke if the death certificate contained stroke as a cause of death and the
      patient had a stroke registered in Riksstroke, the Swedish Stroke Register, in
      the year preceding death. Demographic data at the time of dementia diagnosis was
      compared between patients dying from IS and registered in Riksstroke, patients
      dying from IS without being registered in Riksstroke and those dying from other
      causes. RESULTS: Out of 49823 patients diagnosed with dementia between 2007 and
      2014 in primary care or specialist clinics, 14170 (28.4%) had died by the end of
      2014. Of these 1180 (8.3%) had IS in their death certificate, of which 459
      (38.9%) had been registered in Riksstroke. In patients who died of IS the most
      common type of dementia was vascular dementia while those died from other causes
      were most often diagnosed with Alzheimer's dementia (AD). Patients who died from
      IS and were registered in Riksstroke had higher MMSE score compared to other
      groups. Patients who died from IS took more cardiovascular medications. There
      were no differences in the use of antipsychotics, antidepressants,
      acetylcholinesterase inhibitors, memantine, anxiolytics, or hypnotics between the
      groups. CONCLUSIONS: There was a relatively high number of patients who died from
      IS as shown in their death certificate but had not been registered in Riksstroke
      in the year before death. This creates concerns on the accuracy of death
      certificate stroke diagnoses, particularly for deaths taking place outside
      hospitals.

PMID- 30280667
TI  - Cardiovascular risk in perimenopausal women.
AB  - Cardiovascular disease, and particularly coronary heart disease (CHD), has a low
      incidence in premenopausal women. Loss of ovarian hormones during the
      perimenopause and menopause leads to a sharp increase in incidence. Although most
      CHD risk factors are common to both men and women, the menopause is a unique
      additional risk factor for women. Sex steroids have profound effects on many CHD
      risk factors. Their loss leads to adverse changes in lipids and lipoproteins,
      with increases being seen in low density lipoprotein (LDL) cholesterol and
      triglycerides, and decreases in high density lipoprotein (HDL) cholesterol. There
      is a reduction in insulin secretion and elimination, but increases in insulin
      resistance eventually result in increasing circulating insulin levels. There are
      changes body fat distributionwith accumulation in central and visceral fat which
      links to the other adverse metabolic changes. There is an increase in the
      incidence of hypertension and of type 2 diabetes mellitus, both major risk
      factors for CHD. Oestrogens have potent effects on blood vessels and their loss
      leads to dysfunction of the vascular endothelium. All of these changes resulting
      from loss of ovarian function contribute to the increased development of CHD.
      Risk factor assessment in perimenopausal women is recommended, thereby permitting
      the timely introduction of lifestyle, hormonal and therapeutic interventions to
      modify or reverse these adverse changes.

PMID- 30280668
TI  - HHIV Associated Neurodegenerative Disorders: A New Perspective on the Role of
      Lipid Rafts in Gp120-Mediated Neurotoxicity.
AB  - The implementation of combination antiretroviral therapy (cART) as the primary
      means of treatment for HIV infection has achieved a dramatic decline in deaths
      attributed to AIDS and the reduced incidence of severe forms of HIV-associated
      neurocognitive disorders (HAND) in infected individuals. Despite these advances,
      milder forms of HAND persist and prevalence of these forms of neurocognitive
      impairment are rising with the aging population of HIV infected individuals. HIV
      enters the CNS early in the pathophysiology establishing persistent infection in
      resident macrophages and glial cells. These infected cells in turn secrete
      neurotoxic viral proteins, inflammatory cytokines, and small metabolites thought
      to contribute to neurodegenerative processes. The viral envelope protein gp120
      has been identified as a potent neurotoxin affecting neurodegeneration via
      indirect and direct mechanisms involving interactions with chemokine co-receptors
      CCR5 and CXCR4. This short review focuses on gp120 neurotropism and associated
      mechanisms of neurotoxicity linked to chemokine receptors CCR5 and CXCR4 with a
      new perspective on plasma membrane lipid rafts as an active participant in gp120
      mediated neurodegeneration underlying HIV induced CNS pathology.

PMID- 30280669
TI  - Natural Starch in Biomedical and Food Industry: Perception and Overview.
AB  - Utilization of the native starch is increasing globally because of its wide
      distribution and occurring naturally. Starch is mainly abundant in tubers and
      food grains. Scientific research on starch is increasing in recent years due to
      their unique physiochemical and biomedical properties. Native starch is an
      emerging biopolymer and copolymer in front of biomedical and pharmaceutical areas
      due to their renewability, biocompatibility, biodegradability and their relative
      inexpensiveness. There is increasing interest in natural starches to design and
      produce diverse products due to their pertinent structural properties and non
      toxicity. Due to these attributes, these natural polymers are becoming functional
      core material for different applications including biomedical, construction
      materials, medicine industry, food industry and food supplements, food packaging,
      and carrier for active drugs. So in this paper, we mainly attempt to analyze the
      physicochemical attributions and the biomedical applications on native or non
      conventional starches obtained from the natural botanical sources.

PMID- 30280670
TI  - Iron Bisglycinate Chelate and Polymaltose Iron for the Treatment of Iron
      Deficiency Anemia: a Pilot Randomized Trial.
AB  - BACKGROUND: Iron deficiency anemia (IDA) is a major public health problem
      worldwide. Iron bisglycinate chelate (FeBC) and polymaltose iron (FeP) are used
      for the treatment of IDA and exhibit good tolerability with a low incidence of
      adverse effects. However, these compounds have important differences in their
      structures and bioavailability. OBJECTIVE: To compare the efficacy of oral
      supplementation with FeBC and FeP in anemic children. METHODS: In this double
      blind study, children aged 1 to 13 years who were diagnosed with IDA were
      randomly divided into two groups: i) FeBC, supplemented with iron bisglycinate
      chelate, and ii) FeP, supplemented with polymaltose iron (3.0 mg iron/kg body
      weight/day for 45 days for both groups). RESULTS: Both treatments resulted in
      significant increases in hemoglobin levels, mean corpuscular volume (MCV) and
      cell distribution width (RDW) and in a reduction of transferrin levels, relative
      to initial values. However, only FeBC treatment significantly increased ferritin
      and mean corpuscular hemoglobin (MCH) levels. A significant negative correlation
      was observed between the increase in ferritin and initial hemoglobin levels in
      the FeBC group, indicating that the absorption of FeBC is regulated by the body
      iron demand. CONCLUSION: These results provide preliminary evidence to suggest a
      greater efficacy of FeBC than FeP in increasing iron stores.

PMID- 30280671
TI  - 3D-QSAR and molecular docking studies on oxadiazole substituted benzimidazole
      derivatives: Validation of experimental inhibitory potencies towards COX-2.
AB  - ? Background: In past few decades, computational chemistry has seen significant
      advancements in design and development of novel therapeutics. Benzimidazole
      derivatives showed promising anti-inflammatory activity through the inhibition of
      COX-2 enzyme. ? Objective: The structural features necessary for COX-2 inhibitory
      activityfor a series of oxadiazole substituted benzimidazoles were explored
      through3D-QSAR, combinatorial library generation (Combi Lab) and molecular
      docking. ? Method: 3D-QSAR (using kNN-MFA (SW-FB) and PLSR (GA) methods) and
      Combi Lab studies were performed by using VLife MDS Molecular Design Suite. The
      molecular docking study was performed by using AutoDockVina. ? Results:
      Significant QSAR models generated by PLSR exhibited r2 = 0.79, q2 = 0.68 and
      pred_r2 = 0. 84 values whereas kNN showed q2 = 0.71 and pred_r2 = 0.84. External
      validation of developed models by various parameters assures their reliability
      and predictive efficacy. A library of 72 compounds was generated by combinatorial
      technique in which 11 compounds (A1-A5 and B1-B6) have shown better predicted
      biological activity than the most active compound 27 (pIC50 = 7.22) from the
      dataset. These compounds showed proximal interaction with amino acid residues
      like TYR355 and/or ARG120 on COX-2(PDB ID: 4RS0). ? Conclusion: The present work
      resulted in design of more potent benzimidazoles as COX-2 inhibitors with good
      interaction as compared to reference ligand. The results of the study may be
      helpful in the development of novel COX-2 inhibitors for inflammatory disorders.

PMID- 30280672
TI  - Broad Spectrum Peptide Vaccine Design against Hepatitis C Virus.
AB  - Hepatitis C virus infection is a global burden. Vaccination is the main proposed
      modality to control this disease. No peptide vaccine has been released to market
      due to weak cellular immune responses and the limitation of vaccine ability to
      induce humoral immune responses. Five predominated HCV subtypes in Indonesia (1a,
      1b, 1c, 3a, and 3k) were aligned and the conserved regions were selected. All
      conserved regions were undergone epitopes prediction for class I HLA, class II
      HLA, and B cells. Twenty class I HLA ranging from HLA-A, HLA-B, to HLA-C were
      used to predict the potential epitopes by using NetMHCPan and IEDB. Eight HLA
      DRB1 and combination of 3 HLA-DQA1 and 5 HLA-DQB1 were utilized for Class II
      epitopes prediction by using NetMHCIIPan and IEDB. LBtope and IgPred were used to
      predict B cells epitopes. For Class I HLA, proteasome analysis was performed by
      NetCTL and stability of the epitopes to HLA binding was calculated by using
      NetMHCStabPan. All predicted epitopes were analyzed for antigenicity, toxicity,
      and stability. Population coverage was calculated for several best epitopes. Two
      best epitopes from E2 (Envelope 2) protein, GHRMAWDMMMNWSP and PALSTGLIHLHQN were
      selected as B cells and CD8+ T cell inducer. Other two peptides, LGIGTVLDQAETAG
      and VLVLNPSVAATLGF, taken from NS3 protein were selected as CD4+ T Cell inducer.
      This study suggested the utilization of all four peptides above to make a
      combinational peptide vaccine for in vivo study to prove its ability to induce
      secondary response to prevent HCV infection.

PMID- 30280673
TI  - Image-based QSAR model for prediction of P-gp inhibitory activity of
      epigallocatechin and gallocatechin derivatives.
AB  - BACKGROUND: Permeability glycoprotein (P-gp) is one of the cell membrane proteins
      that can pushed some drugs out of the cell and it causes drug tolerance and its
      inhibition can prevent drug resistant. OBJECTIVE: In this study, we used image
      based quantitative structure-activity relationship (QSAR) models to predict the P
      gp inhibitory activity of epigallocatechin and gallocatechin derivatives.
      METHODS: The 2D-chemical structures and their P-gp inhibitory activity were taken
      from literature. The pixels of images and their principal components (PCs) were
      calculated using MATLAB software. Principle component regression (PCR),
      artificial neural network (ANN) and support vector machine (SVM) approaches were
      used to develop QSAR models. Statistical parameters included the leave one out
      cross-validated correlation coefficient (q2) for internal validation of the
      models and R2 of test set, root mean square error (RMSE) and concordance
      correlation coefficient (CCC) were applied for external validation. RESULTS: Six
      PCs from image analysis method were selected by stepwise regression for
      developing linear and non-linear models. Non-linear models i.e. ANN (with the R2
      of 0.80 for test set) were chosen as the best for the established QSAR models.
      CONCLUSION: According to the result of the external validation, ANN model based
      on image analysis method can predict the P-gp inhibitory activity of
      epigallocatechin and gallocatechin derivatives better than the PCR and SVM
      models.

PMID- 30280674
TI  - Synthesis, Anti-inflammatory Activity and Docking Studies of Some Newer 1,3
      Thiazolidine-2,4-dione Derivatives as Dual Inhibitors of PDE4 and PDE7.
AB  - BACKGROUND: Phosphodiesterase 4 (PDE4) and phosphodiesterase 7 (PDE7), members of
      PDE superfamily, catalyse hydrolysis of cyclic adenosine monophosphate in pro
      inflammatory and immunomodulatory cells leading to increased inflammatory
      processes. Dual inhibitors of PDE4 and PDE7 are a novel class of drug candidates
      which can regulate pro-inflammatory as well as immune T-cell function and can be
      particularly useful in the treatment of a wide variety of immune and inflammatory
      disorders with less undesirable adverse effects. OBJECTIVE: The present research
      work was designed to synthesize and evaluate the anti-inflammatory activity as
      well as in silico docking studies of some newer substituted 1,3-thiazolidine-2,4
      dione derivatives as dual inhibitors of PDE4-PDE7. METHOD: A new series of
      substituted 1,3-thiazolidine-2,4-dione derivatives was synthesized and evaluated
      for anti-inflammatory activity in animal models followed by docking studies to
      determine the binding interactions for the best fit conformations in the binding
      site of PDE4 and PDE7 proteins. RESULTS: Amongst the synthesized molecules,
      compounds 5 and 12 showed higher anti-inflammatory activity in the carrageenan
      induced rat paw oedema method. The in vivo experimental results were found to be
      in concordance with that of the in silico results. CONCLUSION: These molecules
      can act as the starting hits for the design of safe and effective dual inhibitors
      of PDE4 and PDE7 for the potential treatment of various inflammatory disorders.

PMID- 30280675
TI  - Integrin alpha6 (CD49f), The Microenvironment and Cancer Stem Cells
AB  - Cancer is a highly prevalent and potentially terminal disease that affects
      millions of individuals worldwide. Here, we review the literature exploring the
      intricacies of stem cells bearing tumorigenic characteristics and collect
      evidence demonstrating the importance of integrin &alpha;6 (ITGA6, also known as
      CD49f) in cancer stem cell (CSC) activity. ITGA6 is commonly used to identify CSC
      populations in various tissues and plays an important role sustaining the self
      renewal of CSCs by interconnecting them with the tumorigenic microenvironment.

PMID- 30280676
TI  - Recent biomedical applications on stem cell therapy: A brief overview.
AB  - The unique self-renewal and differentiation ability of stem cells drag the
      attention of many scientists and researchers towards the clinical application of
      stem cells. Stem cells are basically the normal living cells of multicellular
      organisms with some special ability to proliferate and transform into any kind of
      the body cells with their characteristic feature. Talking about human stem cells,
      it is originated from various sources like embryonic stem cells, somatic stem
      cells, hematopoietic stem cells, bone marrow stem cells, neural stem cells etc.
      which differs in their differentiation potency. On the basis of their potency
      they can be applied in treatment or regeneration of different cells. Stem cell
      therapy having very wide range application in treatment of various diseases. In
      this review article we have summarized the application of stem cell as
      regenerative medicine and treatment of chronic disorders.

PMID- 30280677
TI  - Stem cell-based therapies: A New ray of hope for diabetic patients.
AB  - Diabetes and its complications are a significant health concern throughout the
      globe. There are physiological differences in the mechanism of type-I and type-II
      diabetes and the conventional drug therapy as well as insulin administration seem
      insufficient to address the problem at large successfully. Hypoglycemic swings,
      frequent dose adjustments and resistance to the drug are major problems
      associated with drug therapy. Cellular approaches through stem cell based
      therapeutic interventions offer a promising solution to the problem. The need for
      pancreatic transplants in case of Type-I diabetes can also be by-passed/reduced
      due the formation of insulin producing beta cells via stem cells. Embryonic stem
      cells and (ESCs) and induced pluripotent stem cells (iPSCs), successfully used
      for generating insulin producing beta cells. Although many experiments have shown
      promising results with stem cells in vitro, their clinical testing still needs
      more exploration. The review attempts to bring into light clinical studies
      favoring the transplantation of stem cells in diabetic patients with an objective
      of improving insulin secretion and improving degeneration of different tissues in
      response to diabetes. It also focuses on the problems associated with successful
      implementation of the technique and possible directions for future research.

PMID- 30280678
TI  - Theranostic platforms proposed for cancerous stem cells: A review.
AB  - It is a near-to-impossible not to accept that cancer takes position as the main
      cause of global burden of disease, for it is hard to ignore the outnumbered
      people dying from cancer. Looking at the statistics proves that progress in
      cancer therapy is always beyond cancer in a race of pessimism about the future;
      for various kinds of cancers yearly cause death in the world, whereas the
      conventional and even modern therapies often exhibit lack of reliability in
      treatment of cancer. In principal, various reasons are identified for cancer
      resistance and recurrence. Recognizing the cells/tissue from which cancer takes
      origin enables its early detection, and optimistically saying protection of
      patients against death. It has been recognized that cancer stem cells are
      responsible for cancer cell proliferation and metastasis. Conventional therapies
      cannot eradicate the cancer stem cell; therefore, cancer recurrence is
      unavoidable. In this regards, designing smart platforms with specific properties
      is an essential step in cancer treatment. Theranostic platforms have been
      facilitated the cancer diagnosis and treatment, simultaneously. In this respect,
      several sorts of smart materials have been designed to detect and cure the
      cancer. Cancer stem cell as a root of the cancerous tumor should be eradicated to
      achieve the complete treatment; hence, cancer stem cell mechanism must be known
      precisely to architect the appropriate platform making possible to encounter with
      cancer stem cell. In this review paper, various therapeutic and diagnostic
      techniques of cancerous stem cell are discussed to pave a way for designing
      proper platforms for cancer eradication.

PMID- 30280679
TI  - Lifestyle patterns as a modifiable risk factor for late-life cognitive decline: a
      narrative review regarding dementia prevention.
AB  - BACKGROUND: Dementias due to neurodegenerative disorders and more specifically,
      Alzheimer's disease (AD) are the most frequent of all diseases within the
      industrialized world. Besides this alarming fact, it is noted too that almost
      three-quarter of people with AD reside in low or middle-income nations. In recent
      years, cognitive and behavioral neuroscientists have focused on a possible
      correlation between environmental agents and genetic risk factors for these
      dementias. METHOD: In this narrative review, a close review of Medical Literature
      Analysis and Retrieval System was conducted. The authors aimed at analyzing
      possible interactions between lifestyle patterns and major risk factors
      responsible for cognitive decline and dementia, considering that the prevention
      or treatment of midlife modifiable risks may possibly reduce population-wide late
      life pathological neurodegeneration. RESULTS: This review focuses on modifiable
      risk factors for late-life cognitive decline. A growing number of studies have
      indicated that the impact of genetics and epigenetic factors on dementia risk is
      dependent on different lifestyle factors, ranging from leisure activities and
      nutritional habits, through to social interaction and toxic exposure. CONCLUSION:
      Despite all evidence regarding modifiable risk factors possibly reducing the risk
      of developing dementia in later life, many unanswered questions remain regarding
      the direct influence of these variables in later life. People who regularly and
      actively participate in different lifelong activities (social, cultural and
      intellectual) do tend to perform better on formal cognitive tests, experience
      fewer cognitive complaints, and are less likely to develop neurodegenerative
      disorders.

PMID- 30280680
TI  - Hyperkinetic disorder in a community service for people with intellectual
      disability.
AB  - BACKGROUND: There appears to be a higher rate of prevalence of hyperkinetic
      disorder in the intellectual disability (ID) population, although there is a
      large variability in rates in previous studies. Hyperkinetic disorder can be a
      challenge to diagnose in a population with ID and can present a barrier to the
      development of the activities of daily living in an already vulnerable
      population. OBJECTIVES: Our objective was to examine the point prevalence of
      hyperkinetic disorder in the ID population in a community ID service and also to
      determine the prevalence of hyperkinetic disorder based on the level of ID.
      METHODS: A cross-sectional review of the Online Information Service 'OLIS'
      database was undertaken to establish the total number of patients with ID and
      those with comorbid hyperkinetic disorder. The overall point prevalence and
      prevalence based on the level of ID was calculated from the collected data.
      RESULTS: The point prevalence of hyperkinetic disorder in the population with ID
      was similar to that found in studies in the general population at 3.1% in adults
      and 32.6% in children. When divided by the level of disability, the calculated
      point prevalence in both adults and children was highest in the population with
      mild ID and decreased as the level of disability increased. CONCLUSION: This
      report contributes to previous research establishing the rates of hyperkinetic
      disorder in an ID population and establishes the point prevalence of hyperkinetic
      disorder in individuals diagnosed with ID in a clinical sample.

PMID- 30280681
TI  - Climatic influences on the mortality of sheep during long-distance sea transport.
AB  - Research on the causes of sheep death in sea voyages from Australia to the Middle
      East is limited, in particular little is known about the influence of climatic
      factors. Mortality data from 417 shipments of sheep exported over an 11-year
      period (November 2004 to June 2015) were modelled retrospectively to determine
      associated climatic factors. The statistical analysis were performed for both the
      full data set with 417 voyages based on actual and estimated departure and
      arrival dates and a restricted data set with 71 voyages based on actual dates.
      The results of the full data set demonstrated a seasonal mortality pattern, with
      more deaths occurring on sea voyages leaving Australia in the southern hemisphere
      winter or spring than those departing in Australian summer or autumn. Heat stress
      and inadequate fat mobilisation for energy supply when sheep are inappetant on
      shipments may explain this seasonality. Based on these two models, the voyage and
      weather factors associated with sheep mortalities included departure year, autumn
      departure in the southern hemisphere, voyage duration, single or multiple loading
      port(s), weekly mean dry bulb temperature and wind speed at departure ports, and
      humidity at destination ports. Significant correlations were observed between
      weather variables at the departure ports in the Australian winter and a high
      sheep mortality rate during voyages. This, together with the anticipated
      increased heat stress risk as a result of climate change, suggests that there
      could be review of the trade from Australia in the southern hemisphere winter.
      The influence of weather at the departure ports should be considered in sheep
      mortality prediction models, especially Australia's heat stress risk assessment
      model.

PMID- 30280682
TI  - Mitochondrial activity and cytoskeleton organization in three pronuclei oocytes
      after intracytoplasmic sperm injection.
AB  - SummaryDigyny, the presence of a third pronucleus due to the failure of second
      polar body extrusion, is problematic after intracytoplasmic sperm injection
      (ICSI) practices. Mitochondria have critical roles such as production of
      adenosine triphosphate (ATP) and regulation of Ca2+ homeostasis during oocyte
      maturation, fertilization and the following development, while the regulation of
      meiotic spindle formation, chromosome segregation, pronuclear apposition and
      cytokinesis is closely associated with the cytoskeleton. In this study,
      mitochondrial membrane potential, distribution of F-actin and gamma-tubulin, and
      the ultrastructure of three pronuclear (3PN) oocytes were investigated. 3PN
      oocytes after ICSI procedure were taken from patients who were enrolled in
      assisted reproduction programmes. For mitochondrial membrane potential analysis,
      fresh oocytes stained with the mitochondrial membrane potential probe JC-1, were
      evaluated under fluorescence microscopy. The mitochondrial membrane potential of
      three pronuclear oocytes showed similar results to normal zygotes. gamma-Tubulin
      was stained strongly at the subplasmalemmal domain and microfilaments were
      localized at the cortical, but not the perinuclear, area. Cytoplasmic halos were
      moderately or not detected by electron microscopy; lipofuscin granules,
      degenerated mitochondria, and multilamellated bodies were seen in the ooplasm.
      Immunohistochemistry and electron microscopic findings suggested that
      mitochondrial membrane potential has no direct effect on second polar body
      extrusion. This abnormality can be associated with an altered cytoskeleton due to
      poor oocyte quality.

PMID- 30280683
TI  - Estimating development and temperature thresholds of Ephestia kuehniella: toward
      improving a mass production system.
AB  - The development of the Mediterranean flour moth, Ephestia kuehniella (Zeller),
      was evaluated at 10, 15, 17.5, 20, 22.5, 25, 27.5, 30 and 32.5 degrees C with no
      lighting. None successfully completed development at 10 and 32.5 degrees C. The
      total development time from egg to adult emergence was 164, 140, 98, 76, 61, 62
      and 50 days, respectively, at the remaining temperatures. The developmental rate
      of E. kuehniella was described by the common linear model and six non-linear
      models. The lower temperature threshold for the immature stages and the thermal
      constant for E. kuehniella were 9 degrees C and 1111 degree-days (DD) to complete
      development from egg to newly emerged adult. Non-linear models estimated the
      lower and upper thermal thresholds (Tmin and Tmax) and optimal temperature
      (Topt). The values of Tmax calculated by three nonlinear models ranged from 34
      degrees C to 46 degrees C; Topt for each stage of development varied from 24 and
      31 degrees C, consistent with the temperature (30 degrees C) at which the most
      rapid development occurred. Information on the threshold temperatures for
      development and thermal requirements can be utilized to predict E. kuehniella
      population dynamics and phenology and to evaluate optimal temperature conditions
      for mass rearing in stored products.

PMID- 30280684
TI  - Maturational gene upregulation and mitochondrial activity enhancement in mouse in
      vitro matured oocytes and using granulosa cell conditioned medium.
AB  - SummaryThe high miscarriage rates that result following transfer of embryos
      derived from in vitro maturation (IVM) of oocytes necessitate improvements in the
      processes involved. This study aimed to improve the quality of in vitro matured
      oocytes using granulosa cell conditioned medium (GCCM) as the culture medium. In
      this work, germinal vesicle (GV)-stage oocytes from NMRI mice were collected and
      cultured using three types of culture medium: Base medium (BM) (control), 50%
      granulosa cell conditioned medium (GCCM50) and 100% GCCM (GCCM100). After IVM,
      the mitochondria activity potential and viability of metaphase II (MII) oocytes
      were evaluated by JC-1 and trypan blue staining, respectively. Maturational gene
      expression levels of CyclinB1, Cdk1 and Gdf9 in the control, GCCM50 and GCCM100
      samples were analyzed using real-time polymerase chain reaction (PCR). The
      viability rate of in vitro matured oocytes was highest in the GCCM50 group. JC-1
      staining showed that GCCM50 enhances mitochondrial activity more than the other
      groups (P < 0.05). Gene expression levels of Cdk1 and Gdf9 were higher in the
      group with GCCM50 treatment, than in the control and GCCM100 groups (P < 0.05),
      while the expression level of CyclinB1 did not differ among the groups. The
      results indicated that a 50% concentration of GCCM in combination with BM
      components enhanced MII and viability rates and mitochondria activity of mouse
      immature oocytes.

PMID- 30280686
TI  - In the national epidemiological bulletins - a selection from recent issues.

PMID- 30280688
TI  - Uptake and effectiveness of influenza vaccine in those aged 65 years and older in
      the United Kingdom, influenza seasons 2010/11 to 2016/17.
AB  - BackgroundIn 2016/17, seasonal influenza vaccine was less effective in those aged
      65 years and older in the United Kingdom. We describe the uptake, influenza
      associated mortality and adjusted vaccine effectiveness (aVE) in this age group
      over influenza seasons 2010/11-2016/17. Methods: Vaccine uptake in 2016/17 and
      five previous seasons were measured using a sentinel general practitioners cohort
      in England; the test-negative case-control design was used to estimate pooled aVE
      by subtype and age group against laboratory-confirmed influenza in primary care
      from 2010-2017. Results: Vaccine uptake was 64% in 65-69-year-olds, 74% in 70-74
      year-olds and 80% in those aged 75 and older. Overall aVE was 32.5% (95% CI: 11.6
      to 48.5); aVE by sub-type was 60.8% (95% CI: 33.9 to 76.7) and 50.0% (95% CI:
      21.6 to 68.1) against influenza A(H1N1)pdm09 and influenza B, respectively, but
      only 5.6% (95% CI: - 39.2 to 35.9) against A(H3N2). Against all laboratory
      confirmed influenza aVE was 45.2% (95% CI: 25.1 to 60.0) in 65-74 year olds; -
      26.2% (95% CI: - 149.3 to 36.0) in 75-84 year olds and - 3.2% (95% CI: - 237.8 to
      68.5) in those aged 85 years and older. Influenza-attributable mortality was
      highest in seasons dominated by A(H3N2). Conclusions: Vaccine uptake with non
      adjuvanted, normal-dose vaccines remained high, with evidence of effectiveness
      against influenza A(H1N1)pdm09 and B, though poor against A(H3N2), particularly
      in those aged 75 years and older. Forthcoming availability of newly licensed
      vaccines with wider use of antivirals can potentially further improve prevention
      and control of influenza in this group.

PMID- 30280690
TI  - Toxoplasma gondii IgG Seroprevalence in Patients with HIV/AIDS.
AB  - OBJECTIVE: Toxoplasmosis is a common opportunistic infection in patients with
      HIV/AIDS and may cause life-threatening clinical courses, such as encephalitis
      and pneumonia. METHODS: Patients admitted between January 2006 and August 2017
      with anti-HIV positivity confirmed by Western blotting were included in the
      study. Demographic data, CD4+ T-lymphocyte counts, and Toxoplasma gondii IgG/IgM
      levels were retrospectively obtained from patient records. RESULTS: T. gondii IgM
      positivity was not detected in patients, whereas T. gondii IgG positivity was
      detected in 267 (43.5%) patients. The T. gondii IgG positivity rate was 37.6% in
      men who had sex with men (MSM) and 48.4% in heterosexual patients. Furthermore,
      42.6% of MSM and 21% of heterosexual patients were university graduates, of which
      T. gondii IgG positivity was detected in only 33.6% of MSM patients and 42.3% of
      heterosexual patients. CONCLUSION: In our study, high seronegativity was
      remarkable in MSM patients, particularly those who were highly educated, thus
      emphasizing the importance of prevention of primary infection in seronegative
      patients; necessity of prophylaxis in appropriate patients due to encephalitis,
      which has a high mortality rate and almost always develops after a latent
      infection; and necessity of screening for toxoplasmosis seropositivity at the
      time of diagnosis.

PMID- 30280687
TI  - The shift in rabies epidemiology in France: time to adjust rabies post-exposure
      risk assessment.
AB  - The epidemiology of rabies in France and western Europe has changed during the
      past 22 years. In France, rabies in non-flying terrestrial mammals was declared
      to be eliminated in 2001, and the risk of rabies is now limited to contact with
      bats, rabid animals illegally imported from rabies-enzootic countries and
      traveller exposure in enzootic areas. We analysed the epidemiology of rabies in
      France from 1995 to 2016, describing and analysing data on human rabies
      surveillance as well as data on post-exposure prophylaxis (PEP) collected from
      the network of French antirabies clinics. Over the study period, seven
      individuals were diagnosed with rabies in France, all of whom were infected
      outside mainland France. PEP data analysis revealed an expected overall decrease
      in PEP administration for individuals exposed in mainland France, but there was
      still overuse of anti-rabies drugs, given the very low epidemiological risk. On
      the other hand, a significant increase in PEP delivered to individuals exposed
      abroad was evidenced. These epidemiological trends indicate that clear guidelines
      should be provided to support physicians' efforts to adjust rabies risk
      assessment to the evolution of the epidemiological situation.

PMID- 30280689
TI  - Transmission of toxigenic Corynebacterium diphtheriae by a fully immunised
      resident returning from a visit to West Africa, United Kingdom, 2017.
AB  - In early 2017, a United Kingdom (UK)-born person in their 20s presented with a
      skin ulcer on the foot 3 weeks after returning from Ghana. The patient had last
      received a diphtheria-containing vaccine in 2013, completing the recommended
      course. MALDI-TOF of a cutaneous swab identified Corynebacterium diphtheriae.
      Real-time PCR ascertained the species and presence of the diphtheria toxin gene.
      An Elek test confirmed toxigenicity. The isolate was macrolide sensitive and
      penicillin resistant. The local Public Health England (PHE) Health Protection
      Team obtained the patient's clinical history and traced contacts to inform
      appropriate public health action. One close contact (in their early 80s with
      uncertain immunisation status who had not recently travelled) had a positive
      throat swab for toxigenic C. diphtheriae and reported a history of mild coryzal
      symptoms. Multilocus sequence typing revealed that strains from the index case
      and contact had Sequence Type 463. Diphtheria is extremely rare in the UK due to
      high vaccine coverage and this is the first documented transmission in 30 years.
      Clinicians and laboratory staff should remain highly suspicious of lesions in
      overseas travellers, even when patients are fully vaccinated. Older individuals
      who might not have completed a full immunisation course may have higher
      diphtheria susceptibility.

PMID- 30280691
TI  - Intestinal Protozoa in Hiv-Infected Patients: A Retrospective Analysis.
AB  - OBJECTIVE: Intestinal parasitic infections are common in immunodeficient
      patients. In developing countries, the incidence of diarrhea due to parasitic
      infections in HIV (human immunodeficiency virus)-positive individuals is reported
      to be over 90%. The present study aimed to investigate the presence of intestinal
      protozoa in HIV-positive patients with gastrointestinal complaints. METHODS: The
      fecal samples of 65 HIV-positive patients (14 women, 51 men) were included.
      Clinical data obtained from patients' files and laboratory results were
      retrospectively scanned using laboratory information system. Age, sex, parasite
      positivity, CD4+ count, HIV RNA level, and antiretroviral therapy information
      were recorded. RESULTS: Fourteen Cryptosporidium spp. (21.5%), 2 Cyclospora spp.
      (3.1%), 7 Blastocystis spp. (10.8%), and 1 Cryptosporidium spp.+Blastocystis spp.
      (1.5%) were detected. The median duration of antiretroviral treatment was 3
      months and 12 months in patients with and without parasites in fecal samples,
      respectively. The duration of antiretroviral treatment was significantly higher
      in non-infected patients (p=0.002). No significant correlations were found
      between parasite presence and CD4+ T cell counts or HIV RNA levels. CONCLUSION:
      Our findings suggest that positive effects of antiretroviral therapy on the
      immune system of HIV-infected patients reduce the risk of intestinal parasitic
      infection, and thus, this treatment may play an important role in protection.

PMID- 30280692
TI  - Prediction of Cutaneous Leishmaniasis Epidemiology in Mersin Using Ecological
      Niche Modeling.
AB  - OBJECTIVE: In our study, we aimed to develop an ecological niche model showing
      current distribution of cutaneous leishmaniasis (CL) by using location
      information on 630 cases of CL reported in the Mersin province between 2005 and
      2015 and bioclimatic and environmental variables. METHODS: The ecological niche
      model was based on interpretation of patient locations and climatic data entered
      in geographical information systems and maximum entropy databases. RESULTS: In
      the model produced for the Mersin province, the area under the curve was
      calculated as 0.918. Also, the mean temperature of the driest quarter (BIO9),
      mean temperature of the warmest quarter (BIO10), and maximum temperature of the
      warmest month (BIO5) were determined as climatic factors that are most effective
      for CL distribution. CONCLUSION: There is a relationship between distribution of
      CL and climatic factors in the Mersin province. The developed model will
      contribute to better understanding of epidemiology and control of vector-borne
      diseases by authorities in the ministry of health.

PMID- 30280693
TI  - Light Microscopy and Scanning Electron Microscopy of Colpocephalum nanum Piaget,
      1890 (Phthiraptera: Amblycera: Colpocephalidae).
AB  - OBJECTIVE: The aim of this study was to examine the morphological characteristics
      of Colpocephalum nanum (C. nanum) Piaget, 1890 using light microscopy (LM) and
      scanning electron microscopy (SEM). METHODS: For this purpose, the C. nanum
      specimens collected from long-legged buzzards, Buteo rufinus (B. rufinus)
      (Accipitriformes: Accipitridae), in Turkey were examined under LM and SM for
      morphological characteristics. The specimens were fixed and kept in 70% ethanol,
      cleared and mounted on the slides in Canada balsam. They were examined for
      morphological characteristics under LM. Some of the samples were put in a plate
      on absorbing paper and kept overnight, for ether to evaporate. These samples were
      mounted on aluminum stubs to study the ventral surface by placing them on their
      dorsal or ventral surface on double-sided adhesive tape. They were sputter-coated
      three times with gold, each time for approximately 7 minutes and later viewed
      using SEM (Zeiss SUPRA 55 VP FE-SEM and Zeiss EVO lS 10). RESULTS: Parts of the
      specimens were photographed, and the obtained data about morphological
      characteristic were evaluated in detail. CONCLUSION: The LM and SEM photos of C.
      nanum were compared, and information about the important criteria for diagnosis
      and other morphological characteristics was obtained.

PMID- 30280694
TI  - Insecticidal, Oxidative, and Genotoxic Activities of Syzygium aromaticum and
      Eucalyptus globulus on Culex pipiens Adults and Larvae.
AB  - OBJECTIVE: The wide-reaching Culex pipiens has long been a public apprehension.
      Combating serious vector-borne diseases requires the use of insecticides
      effective against both humans and the ecosystem. The wide variation of botanicals
      that nature has to offer tempts researchers to study their interactions with the
      insects. Environment-friendly insecticides light up hope for maintaining
      ecological balance and pollution mitigation. This study aimed at evaluating the
      insecticidal, oxidative, and genotoxic activities of eucalyptus and clove oils on
      C. pipiens adults and larvae. METHODS: The chemical composition of essential oils
      was determined via gas chromatography/mass spectrometry. The bioassay was
      performed, with eucalyptus oil showing the highest toxicity index (LC50 of 0.108%
      after 24 h in adults and LC50 of 0.014% after 48 h in larvae). RESULTS:
      Fumigation effects showed Eucalyptus to have higher toxicity than clove oil, with
      an LC50 of 0.108% and 0.014% after 24 h and 48 h, respectively, in adults and
      larvae. The effect of tested oils on the activities of glutathione peroxidase,
      catalase, and superoxide dismutase varied with increasing oil concentrations. The
      genotoxic effects of the tested oils were dose-dependent, with an increase of all
      comet parameters compared with those in the control. CONCLUSION: The tested oils
      showed encouraging potentiality as green insecticides in combating C. pipiens.

PMID- 30280696
TI  - Myiasis Phenomenon in a Patient Receiving Maggot Debridement Therapy.
AB  - OBJECTIVE: Classical treatment was administered on the wound on the left foot of
      the patient, but no improvement was observed. When advised to undergo amputation,
      the patient came to the wound care unit to treat the larval wound. It was
      observed that the wound had been wormed while the patient was undergoing larval
      treatment. Interestingly, this incidental encounter was thought to be appropriate
      for case presentation. METHODS: The larvae seen in the left hand of the patient
      were removed using forceps and sent to a laboratory. The larvae as well as adult
      flies obtained from them were examined directly and stereomicroscopically, their
      photographs were captured, and they were typed. RESULTS: The larvae in the third
      stage and adult flies were identified as Sarcophaga sp. CONCLUSION: Hygiene
      deficiency, inadequate sanitation, and improper wound care are important factors
      responsible for myiasis formation. We believe that myiasis can be avoided if
      adequate sanitation and hygiene and appropriate and regular wound care are
      provided.

PMID- 30280695
TI  - Molecular Characterization of Myiasis-Causing Moth Flies (Diptera: Psychodidae).
AB  - OBJECTIVE: The aim of this study is to examine the molecular characterization of
      moth flies (Diptera: Psychodidae) based on their mitochondrial DNA sequences and
      determine the vectorial potential and damage caused by moth flies in future
      researches. METHODS: A total of 240 adult moth flies were collected from toilet,
      bathroom, and basement walls of houses from different locations of the Kayseri
      region between May 2016 and April 2017. The polymerase chain reaction (PCR)
      analyses were performed using primer pairs, specificaly targeting the
      mitochondrial cytochrome oxidase c subunit I (mt-COI) gene of adult flies.
      RESULTS: In total, five isolates were gel purified and sequenced for molecular
      characterization and phylogenetic analyses. Two species, namely Telmatoscopus
      albipunctatus (ERU-Telmatos3 and ERU-Telmatos6) and Psychodidae sp. (ERU
      Psycho1,4,5), were successfully identified with the sequence alignment of
      isolates. According to the phylogenetic analysis, it was determined that the ERU
      Telmatos3 and ERU-Telmatos6 isolates are clustered in the haplogroup A, while the
      ERU-Psycho1,4,5 isolate was clustered within the haplogroup B. The ERU-Psycho1
      isolate was characterized as a new haplotype within the haplogroup B. CONCLUSION:
      This study represents the first molecular characterization and phylogenetic
      status of moth flies in Turkey. The obtained findings should be the first step in
      the future investigation based on detecting the transmission of bacterial
      pathogens by moth flies.

PMID- 30280697
TI  - Detection of Toxoplasma gondii in a Eurasian Badger (Meles meles) Living in
      Wildlife Areas of Izmir, Turkey.
AB  - Toxoplasma gondii is an obligatory intracellular protozoon parasite that causes
      toxoplasmosis in humans and all warm-blooded animals. In this study, we aimed to
      investigate the presence of T. gondii DNA in a Eurasian badger (Meles meles) that
      was found dead in the wildlife area of Izmir. According to the results of real
      time polymerase chain reaction, T. gondii REP gene was found to be positive in
      the Eurasian badger brain homogenate. In conclusion, Eurasian badger, a known
      carnivore, can be a potential source of toxoplasmosis in the natural settings of
      Izmir, Turkey.

PMID- 30280698
TI  - Importance of spin current generation and detection by spin injection and the
      spin Hall effect for lateral spin valve performance.
AB  - Lateral spin valves are attractive device geometries where functional spin
      currents can be generated and detected by various mechanisms, such as spin
      injection and the direct and the inverse spin Hall effect. To understand the
      mechanisms behind these effects better, as well as their potential for
      application in devices, we combine multiple mechanisms in multi-terminal Pt-Py-Cu
      lateral spin valves: we generate pure spin currents in the copper spin conduit
      both via the spin Hall effect in platinum and electric spin injection from
      permalloy and detect signals both via conventional non-local detection and via
      the inverse spin Hall effect in the same device at variable temperatures.
      Differences are observed, which we explain by the different spin injection and
      detection mechanisms, revealing their importance for the temperature dependence,
      which is not just governed by the spin transport in the conduit as previously
      claimed. By determining a different sensitivity of the observed effects on the
      interfaces, we highlight the importance of the exact current path for the device
      operation.

PMID- 30280699
TI  - Prevascularized bladder acellular matrix hydrogel/silk fibroin composite
      scaffolds promote the regeneration of urethra in a rabbit model.
AB  - OBJECTIVE: To evaluate the effects of urethral regeneration with prevascularized
      bladder acellular matrix hydrogel (BAMH)/silk fibroin (SF) composite scaffolds in
      a rabbit model. MATERIALS AND METHODS: BAMH/SF and collagen Type I hydrogel/SF
      (CH/SF) scaffolds were prepared and the structure of the scaffolds was assessed
      using scanning electron microscopy. BAMH/SF, CH/SF and SF scaffolds were
      incubated in the omentum of male rabbits for two weeks and then harvested for
      repairing autologous urethral defects. Histological analysis of the incubated
      scaffolds was performed to evaluate the neovascularization capacity, and the
      outcomes of urethroplasty were evaluated at one and three months post
      operatively. RESULTS: The composited scaffolds were composed of a highly porous
      BAMH or CH buttressed by compact SF outer layer. The histological analysis of the
      incubated BAMH/SF revealed a signifcant increase of the neovascularization among
      three groups after a two-week incubation. At three months, the urethra maintained
      wide caliber in the BAMH/SF group. Strictures were found in the CH/SF and SF
      groups. Histologically, at one month, intact and multilayer epithelium occurred
      in the BAMH/SF group, and one layer epithelium was found in the CH/SF and SF
      groups. However, there was similar epithelial regeneration in BAMH/SF and CH/SF
      groups at three months (p > 0.05). Comparisons of smooth muscle content and
      vessel density among the SF, CH/SF and BAMH/SF revealed a significant increase at
      each time point (p < 0.05). CONCLUSION: Our results demonstrate that incubated
      BAMH/SF promote neovascularization, and prevascularized BAMH/SF promote the
      regeneration of the urethral epithelium and smooth muscle, which indicates its
      potential for urethral reconstruction.

PMID- 30280700
TI  - Unconventional field-effect transistor composed of electrons floating on liquid
      helium.
AB  - We report on an unconventional macroscopic field effect transistor composed of
      electrons floating above the surface of superfluid helium. With this device
      unique transport regimes are realized in which the charge density of the electron
      layer can be controlled in a manner not possible in other material systems. In
      particular, we are able to manipulate the collective behavior of the electrons to
      produce a highly non-uniform, but precisely controlled, charge density to reveal
      a negative source-drain current. This behavior can be understood by considering
      the propagation of damped charge oscillations along a transmission line formed by
      the inhomogeneous sheet of two-dimensional electrons above, and between, the
      source and drain electrodes of the transistor.

PMID- 30280701
TI  - Surface states of gapped electron systems and semi-metals.
AB  - With a generic lattice model for electrons occupying a semi-infinite crystal with
      a hard surface, we study the eigenstates of the system with a bulk band gap (or
      the gap with nodal points). The exact solution to the wave functions of
      scattering states is obtained. From the scattering states, we derive the
      criterion for the existence of surface states. The wave functions and the energy
      of the surface states are then determined. We obtain a connection between the
      wave functions of the bulk states and the surface states. For electrons in a
      system with time-reversal symmetry, with this connection, we rigorously prove the
      correspondence between the change of Kramers degeneracy of the surface states and
      the bulk time-reversal Z 2 invariant. The theory is applicable to systems of
      (topological) insulators, superconductors, and semi-metals. Examples for solving
      the edge states of electrons with/without the spin-orbit interactions in graphene
      with a hard zigzag edge and that in a two-dimensional d-wave superconductor with
      a ([Formula: see text]) edge are given in appendices.

PMID- 30280702
TI  - Protein refractive index increment is determined by conformation as well as
      composition.
AB  - The refractive index gradient of the eye lens is controlled by the concentration
      and distribution of its component crystallin proteins, which are highly enriched
      in polarizable amino acids. The current understanding of the refractive index
      increment ([Formula: see text]) of proteins is described using an additive model
      wherein the refractivity and specific volume of each amino acid type contributes
      according to abundance in the primary sequence. Here we present experimental
      measurements of [Formula: see text] for crystallins from the human lens and those
      of aquatic animals under uniform solvent conditions. In all cases, the measured
      values are much higher than those predicted from primary sequence alone,
      suggesting that structural factors also contribute to protein refractive index.

PMID- 30280703
TI  - Torsion-induced vortex switching and skyrmion-like state in ferroelectric
      nanodisks.
AB  - The controllability of vortex state in ferroelectric nanodisks under the effect
      of external torsion is investigated in this work based on phase-field simulation.
      We discover a novel Bloch skyrmion-like state in ferroelectric nanodisks due to
      the combining effect of the torsion and the depolarization field. Moreover, a new
      strategy is proposed to achieve deterministic switching of the vortex chirality
      in the ferroelectric nanodisks. On the one hand, if a fixed external electric
      field is applied to the nanodisk, the vortex chirality can be switched by the
      torsion force. On the other hand, if we apply a fixed torsion force to the
      nanodisk, the vortex chirality can be readily switched by an external electric
      field. The feasibility of both mechanical and electrical switching of the vortex
      in the ferroelectric nanodisks is based on the trilinear coupling between the
      toroidization, polarization and shear strain of the system. The influences of
      temperature, electric field, torsion, and size of the nanodisk on the control of
      the vortex state are further revealed. Our findings shed light on the practical
      control and application of ferroelectric dipole vortices.

PMID- 30280704
TI  - Role of gut inhabitants on vectorial capacity of mosquitoes.
AB  - Mosquito-borne diseases are spreading at an alarming rate. Globally millions of
      deaths occur due to the diseases transmitted by mosquitoes, next to AIDS and
      tuberculosis. Several methods have been used to control these vectors and the
      diseases caused by them. Earlier studies have shown the potential role of
      mosquito gut inhabitants on disease transmission. Their findings can be used as
      an innovative approach for devising strategies to modify the survival of
      mosquitoes by reducing their lifespan, reproduction and disease transmission
      abilities. In this study, microbiome of the three genera of mosquitoes, namely
      Aedes, Anopheles, and Culex along with their vectorial capacity have been
      reviewed for assessing their role in mosquito control and transmission. Relevant
      articles were accessed using different databases, including LILACS, Embase,
      Science Direct and PubMed from inception to June 2017. The search keywords
      included "Aedes", "Anopheles", "Culex", "gut inhabitants", "vectors", and
      "mosquito". The titles, abstract, and keywords of the retrieved articles were
      screened, and eligible research articles were sorted. The review indicates that
      paratransgenesis may be considered as a versatile and effective strategy to
      eradicate the spurt of mosquito transmitting diseases. Enterobacter species is
      the most common type of gram-negative bacteria associated with the gut of all the
      three genera of mosquitoes. It was found to have a beneficial effect on humans as
      it helps in destroying dreadful disease-transmitting vectors. These symbiotic
      qualities of the microbes need to be thoroughly investigated further to reveal
      their antipathogenic effect on the vector.

PMID- 30280705
TI  - Predictive and diagnostic test accuracy of ultrasonography in differentiating
      severe dengue from nonsevere dengue.
AB  - Diagnosing severe dengue from those who do not develop complication is important
      to prevent death. The objective of this systematic review was to evaluate the
      diagnostic test accuracy of ultrasonography in differentiating severe dengue from
      nonsevere dengue; and to assess if ultrasonography/ultrasound can be used as a
      predictive (screening) and diagnostic tool in the course of dengue infection. An
      electronic search was conducted in different databases via OvidSP platform. The
      included studies were cohort studies between 1995 and 2016 wherein cases were
      confirmed by dengue blood test. Severity of dengue was assessed and compared
      using standard WHO references. The methodological quality of the paper was
      assessed by two independent reviewers by using QUADAS-2 tool. In total 12 studies
      were included in this review after suitable screening. Overall, the studies
      included had a low and unclear risk of bias. Seven out of nine studies that
      compared severe dengue and nonsevere dengue, performed an ultrasonography on
      gallbladder (wall thickness cutoff-3 mm) with a sensitivity of 24.2-100% and a
      specificity of 13.2-98.7%. Other parameters such as splenic subcapsular fluid
      collection, pericardial fluid and hepatic subcapsular fluid collection had a
      specificity of >90%, though the sensitivity was poor. There were insufficient
      evidence that ultrasonography is able to differentiate severe dengue from
      nonsevere dengue accurately. The predictive and diagnostic value of
      ultrasonography could not be concluded due to insufficient reporting on the
      temporality of the ultrasonography performed with regard to the diagnosis.
      However, it might serve as an adjunct investigation to support the clinical
      diagnosis.

PMID- 30280706
TI  - Transcriptional responses of attractin gene in the mosquito Anopheles
      culicifacies: A synergistic neuro-olfactory regulation.
AB  - Background & objectives: Attractin, is a large multi-domain protein which has
      regulatory functions in multiple physiological processes and thus have strong
      therapeutic potential. In invertebrates, it was first identified as a water-borne
      protein pheromone that plays important role in chemical communication and
      coordinates reproductive activities. But its role in mosquitoes/insects remains
      unknown. Our unexpected discovery of attractin homolog from the olfactory tissue
      of Anopheles culicifacies mosquito prompted us to investigate the possible role
      of Ac-attractin (Ac-atrn) in diverse behavioural responses, e.g. feeding, mating
      and other non-genetic stresses. Methods: A homology search analysis was performed
      to identify the full length attractin (Ac-atrn) gene of Anopheles culicifacies
      mosquito. To unravel its molecular function during external and internal
      stresses, extensive real-time PCR was performed in the neuro-olfactory tissues of
      the adult mosquitoes as well as in the larval stages. Further, a behavioural
      assay was conducted to elucidate its role in mosquitoes mating behaviour.
      Results: The results indicated that Ac-atrn is a 3942 bp long transcript which
      encodes a 1313 amino acid protein, having multiple domains including CUB, EGF,
      Keltch, etc, with 80-90% homology to other insect/mosquito homologs. Ac-atrn gene
      was dominantly expressed in the young larvae and its expression was elevated in
      response to the fresh food supply in the starved larvae. Cold stress temporarily
      arrested the expression of Ac-atrn gene. In case of adult mosquitoes, olfactory
      and brain tissue showed relatively higher expression of Ac-atrn than reproductive
      organs. Although, starvation did not yield significant changes in olfactory
      tissues, but aging and nutritional stress modulated Ac-atrn expression in the
      brain tissue. Furthermore, a circadian rhythm dependent change in the expression
      of Ac-atrn of virgin and mated mosquitoes (both sexes), indicates that Ac-atrn
      might also have a pheromone guided role during swarm formation and mating
      behaviour. Interpretation & conclusion: The relative expression profiling of Ac
      atrn gene in the larvae during nutritional and cold stress suggested its possible
      role in mediating chemical communication towards the food source and in thermal
      regulation of young larvae. Similarly, it might have crucial regulatory role in
      the stress management and survival of adult mosquitoes. The results revealed that
      Ac-atrn gene is a global regulator of many physiological processes in mosquitoes
      including stress response and mating behaviour and thus might be a potential
      target to design novel intervention strategy against mosquitoes.

PMID- 30280707
TI  - Comparative proteomics of salivary glands of Anopheles culicifacies mosquitoes
      using tandem mass tag (TMT) mass spectrometry.
AB  - Background & objectives: Salivary gland proteins play a pivotal role in blood
      feeding, epithelial interactions, and parasite transmission in mosquito vectors.
      Anopheles culicifacies is a complex of five sibling species, viz. A, B, C, D, and
      E, with diverse geographical distribution patterns. Among these, sibling species
      B has been identified as poor vector. Exploring the differentially expressed
      salivary proteins in An. culicifacies may potentially identify refractoriness
      factors during malaria parasite maturation and may help to elucidate the
      mechanism of refractoriness. Methods: A comparative proteomic analysis was
      carried out using tandem mass tag (TMT) technology combined with LC-MS/MS mass
      spectrometry and bioinformatics analysis, to identify the differentially
      expressed salivary gland proteins among An. culicifacies species A (susceptible)
      and An. culicifacies species B (refractory) mosquitoes. Results: A total of 82
      proteins were found to be differentially expressed. Out of these, seven proteins
      including TRIO, translation initiation factor 5C, glutathione S-transferase, and
      5' nucleotidase were up-regulated, and 75 proteins including calreticulin,
      elongation factors, fructose biphosphatase, isocitrate dehydrogenase, histone
      proteins and anti-platelet proteins, etc. were down-regulated in refractory
      species. Analysis of KEGG pathways showed that the up-regulated proteins were
      related to fatty acid metabolism and RNA transport pathways. Interpretation &
      conclusion: This comparative proteomic analysis of susceptible and refractory An.
      culicifacies salivary gland proteins identifies the plausible role of the
      differential proteome in immune responses, digestion, energy, and carbon
      metabolic pathways. This information may serve as a basis for future work
      concerning the possible role of these proteins in refractoriness dependent
      metabolic function of mosquitoes.

PMID- 30280708
TI  - Potent antileishmanial activity of chitosan against Iranian strain of Leishmania
      major (MRHO/IR/75/ER): In vitro and in vivo assay.
AB  - Background & objectives: Leishmaniasis is one of the major neglected zoonotic
      parasitic diseases whose treatment and control is very complex. Pentavalent
      antimonials remain the primary drugs against different forms of leishmaniasis,
      however, resistance to antimony and its toxic effects has necessitated the
      development of alternative medications such as use of medicinal plants and
      natural compounds. The aim of the current study was to assess the in vitro and in
      vivo activities of chitosan as a natural resource against Leishmania major.
      Methods: Low molecular weight chitosan, with 95% degree of deacetylation was
      melted in normal saline to a final concentration of 50, 100, 200 and 400 MUg/ml.
      Then, the promastigotes of L. major (Iranian strain) were added to the wells of
      96-well plate and 20 MUl of each concentration was added to the RPMI 1640 medium.
      Live and dead promastigotes were counted after adding 0.1% eosin stain. The
      efficacy of the chitosan was also examined in BALB/c mice infected with Iranian
      strain of L. major. All in vitro experiments were performed in triplicate and the
      results of in vitro and in vivo tests were compared to the acetic acid and NaOH
      as negative control and glucantime as positive control. Results: The low
      molecular weight chitosan was completely effective at concentrations of 100, 200
      and 400 MUg/ml on promastigotes of L. major after 180 min of application.
      Moreover, in the in vivo study, the mean size of dermal lesions significantly
      decreased in the groups treated with the chitosan compared to the control group.
      Interpretation & conclusion: According to the results of the study, it can be
      concluded that chitosan is a potent active compound against L. major and could be
      evaluated as a new antileishmanial drug in the future.

PMID- 30280709
TI  - Schistosoma mansoni infection in human and nonhuman primates in selected areas of
      Oromia Regional State, Ethiopia.
AB  - Background & objectives: The transmission of schistosomiasis, caused by
      trematodes of the genus Schistosoma, relies on freshwater snails that act as an
      intermediate host while human and other mammalian act as the definitive hosts.
      Many non-human primates (NHPs) such as Chlorocebus aethiops (vervet) and Papio
      anubis (baboon) are reported to be infected with Schistosoma mansoni in Ethiopia,
      but the role they play in parasite maintenance and transmission is still not
      clear. The objective of this study was, therefore, to determine the prevalence of
      S. mansoni infection in human and NHPs living in close proximities to villages in
      selected endemic areas of Ethiopia. Methods: In this cross-sectional study, stool
      specimens were collected from 911 humans, and fresh faecal droppings from 106
      NHPs from Bochesa (Ziway), Bishan Gari (Kime) and Finchaa (Camp 7) endemic
      localities in Oromia Regional State, and examined for S. mansoni and other
      helminth infections using Kato-Katz method for human participants and direct
      microscopic examination for NHPs. Results: The prevalence of helminthiasis among
      the human study population was 42.4% (386/911), and for soil-transmitted helminth
      infections (A. lumbricoides, hookworms, and T. trichiura) it was 13.4% (122/911).
      In humans S. mansoni was the predominant parasite, 23.1% (210/911) followed by A.
      lumbricoides, 8.7% (79/911); hookworms, 5.8% (53/911); T. trichiura, 4.8%
      (44/911); Taenia species, 2.2% (20/911); E. vermicularis, 2.1% (19/911); and H.
      nana, 3.2% (29/911). NHPs were found positive for Trichuris species and
      Strongyloides species besides S. mansoni. Interpretation & conclusion: NHPs might
      play a significant role in local transmission and maintenance of S. mansoni
      infection even in the absence of human hosts. This calls for supplementation of
      chemotherapy for schistosomiasis along with measures such as snail control to
      interrupt transmission of the disease from humans to NHPs, and vice-versa.

PMID- 30280710
TI  - Small-scale (Phase II) evaluation of the efficacy and residual activity of
      SumiShield(r) 50 WG (clothianidin 50%, w/w) for indoor residual spraying in
      comparison to deltamethrin, bendiocarb and pirimiphos-methyl for malaria vector
      control in Karnataka state, India.
AB  - Background & objectives: There is an urgent need of introducing new insecticide
      molecules with novel modes of action to counter the ever growing insecticide
      resistance in mosquito vectors. In the present study, a new insecticide molecule,
      SumiShield 50 WG (clothianidin 50%, w/w) was investigated for its efficacy as an
      indoor residual spray along with its residual action in comparison to
      deltamethrin, pirimiphos-methyl and bendiocarb. Methods: The study area included
      three villages in Almatti Dam catchment area in Bagalkot district, Karnataka,
      India. Spraying was done using Hudson sprayers with the following dosages
      Clothianidin, 300 mg AI/m2; deltamethrin, 25 mg AI/m2; bendiocarb, 400 mg AI/m2;
      and pirimiphos-methyl, 1 g AI/m2. Cone bioassays were conducted on cement and mud
      plastered surfaces at fortnightly intervals to assess the bioefficacy and
      residual activity. Mosquito densities in the sprayed houses were recorded at
      regular intervals for assessment of the insecticidal efficacy. Filter paper
      samples collected from the sprayed houses were analyzed for insecticide content
      sprayed on different wall surfaces at the Walloon Agricultural Research
      Institute, Gembloux, Belgium. Results: Chemical content analysis of filter paper
      samples revealed that the applied to target ratios were in the acceptable range
      (1 + 0.5) for all the treatment types. Duration of persistence of effectiveness
      of bendiocarb (>=80% mortality in cone bioassays) was 19 to 21 wk on cement
      plastered surfaces and 15 to 19 wk on mud plastered surfaces. Duration of
      persistence of effectiveness of deltamethrin was 17 to 21 wk on both mud and
      cement plastered surfaces and that of pirimiphos-methyl was 15 to 19 wk. For
      SumiShield, it was 17 to 25 wk on both types of surfaces, indicating slow action
      of SumiShield. The densities of Anopheles culicifacies were lower in bendiocarb
      sprayed houses throughout the observation period, followed by pirimiphos methyl,
      deltamethrin and clothianidin sprayed houses. In case of other mosquitoes also,
      similar trend was observed. Interpretation & conclusion: Considering the
      persistence of effectiveness of SumiShield on sprayed surfaces, effectiveness in
      reducing the density of mosquitoes, operational feasibility, safety and community
      acceptance, the formulation of clothianidin is a better option for IRS for the
      control of insecticide-resistant mosquito vectors.

PMID- 30280711
TI  - Coinfections as an aetiology of acute undifferentiated febrile illness among
      adult patients in the sub-Himalayan region of north India.
AB  - Background & objectives: In India, certain geographic regions witness
      simultaneous outbreaks of two or more diseases like scrub typhus, dengue fever,
      malaria, leptospirosis and chikungunya during monsoon and post-monsoon period,
      sharing common indication of acute febrile illness. The objective of the present
      study was to assess the prevalence of coinfections among patients with acute
      undifferentiated fevers (AUF) admitted in a tertiary care hospital in the
      northern hilly state of Himachal Pradesh, India. Methods: This was a hospital
      based open cohort study conducted over a period of two months (September and
      October) in 2016. All the patients above the age of 18 yr admitted in medical
      wards and fulfilling the definition of AUF were included. The patients diagnosed
      with dual infections were the subjects of the study. Standard guidelines were
      used for case definitions of scrub typhus, dengue, chikungunya, malaria and
      leptospirosis. Results: Dual infections were noted in 16 patients admitted with
      AUF. The most common coinfection was scrub typhus and dengue, reported in 10
      patients. Scrub typhus and leptospirosis coinfection was observed in three
      patients. Dengue and chikungunya was observed in one patient. Scrub typhus,
      dengue and vivax malaria was detected in one patient. Scrub typhus and vivax
      malaria was detected in one patient. Out of the 10 cases positive for both scrub
      and dengue, four had no history of travel outside Himachal Pradesh. All three
      cases positive for both scrub and leptospirosis were indigenous without any
      history of travel outside Kangra, Himachal Pradesh. The outcome of all the
      patients was with full recovery. Interpretation & conclusion: The study
      established the presence of coinfections (mainly dengue fever and leptospirosis)
      as a cause of AUF in the study area, which is a nonendemic region. The role of
      easily available and widely performed serological tests in the aetiological
      diagnosis of AUF is significant. Studies are required to determine the normal
      titres in the local population before using the imported commercially available
      serological tests in the diagnosis of AUF.

PMID- 30280712
TI  - Chikungunya virus outbreak in Sint Maarten: Long-term arthralgia after a 15-month
      period.
AB  - Background & objectives: The first chikungunya (CHIK) epidemic in the Americas
      was reported in December 2013. Chikungunya virus (CHIKV) causes an acute febrile
      illness and is transmitted to humans by Aedes mosquitoes. Although earlier
      studies have described long-term clinical manifestations of CHIK patients
      infected with the East/Central/South African (ECSA) genotype, little is known
      about persistent manifestations in the Caribbean region, for which the Asian
      genotype is responsible. The objective of this study was to describe the presence
      of persisting clinical manifestations, specifically arthralgia, in CHIKV-infected
      patients on the Caribbean Island, Sint Maarten, 15 months after onset of the
      disease. Methods: This retrospective cohort study included confirmed CHIK
      patients that were recorded by the participating general practitioners (GPs)
      during the chikungunya outbreak in 2014 in Sint Maarten. Between March and July
      2015, 15 months after the onset of disease, patients were interviewed via
      telephone about the presence, duration and impact of clinical CHIKV
      manifestations. Results: In total, 56 patients were interviewed (median age 47
      yr), of which 30 (54%) were females. Out of the total interviewed patients, 52
      (93%) reported arthralgia for the first three months after the disease onset, of
      which 23 (44%) patients reported to have persistent arthralgia, 15 months after
      the disease onset. Pain intensity of persistent arthralgia was perceived as mild
      in the majority of patients (n = 14; 60%), moderate in 7 (30%) patients and
      severe in 2 (9%) patients. During the acute phase of disease, most patients had
      to miss school or work (n = 39; 72%) due to clinical CHIKV manifestations and
      reported a negative impact on daily activities (n = 36; 57%). Interpretation &
      conclusion: Results suggested that persisting arthralgia is a frequent
      complication in CHIK patients included in the study. Future research on strain
      specific clinical long-term manifestations and on their impact on daily life of
      patients, in the form of a comparative study between patients and controls, is
      recommended.

PMID- 30280713
TI  - Serological evidence of spotted fever group rickettsiosis in and around
      Puducherry, south India-A three years study.
AB  - Background & objectives: Rickettsial diseases are important re-emerging
      infections that mostly go unnoticed or are misdiagnosed. Though few case reports
      of Indian tick typhus have been reported in Indian literature in the past 10 yr,
      prevalence surveys are few and far between. The objective of this research was to
      study the seroprevalence of spotted fever (SF) group rickettsiosis and its
      coinfection with scrub typhus (ST) in Puducherry region of south India, as these
      two diseases may show similar clinical presentations. Methods: During 2012-2015,
      paired sera of 320 febrile patients were examined for Rickettsia conorii IgM/IgG
      by ELISA and OX19 and OX2 agglutinins by Weil-Felix test. Additionally, patients
      were screened for ST IgM ELISA. Statistical analysis was performed for clinical
      and laboratory parameters in children and adults using Fisher's exact test and
      chi-square test with Yates correction. Results: Out of 320 patients, 142 (44.38%)
      had R. conorii IgM and/or IgG antibodies. Only IgM was present in 72 (22.5%)
      patients, while 36 patients were positive for IgG only and 34 were positive for
      both IgG and IgM. A total of 68 patients (21.25%) showed only OX19 and/or OX2
      antibodies (titres >= 1 : 80). SF and ST coinfection was observed in 47 cases
      (14.69%). Interpretation & conclusion: Seroprevalence of SF in Puducherry was
      found to be quite high (44.38%). ST and SF coinfection was observed in 34.50% of
      the SG IgG positive patients, however, this require further evaluation by PCR to
      rule out cross-reaction or false positivity. At present ELISA seems to be an
      affordable alternative to highly subjective and technically demanding
      immunofluorescence assay (IFA) for serodiagnosis of SF.

PMID- 30280714
TI  - Molecular detection of Dirofilaria immitis in dogs and mosquitoes in Tabasco,
      Mexico.
AB  - Background & objectives: Dirofilaria immitis is a filarial nematode that causes
      heartworm disease in domestic as well as wild canines and felines; and cutaneous
      or pulmonary infections in humans. The purpose of the study was to estimate the
      prevalence of D. immitis in domestic dogs in Tabasco, Mexico and to assay
      mosquitoes temporally and spatially associated with dogs for evidence of
      infection. Methods: Blood was collected from 1050 dogs in 1039 houses during a
      random household survey performed in 2016 and 2017. Genomic DNA was extracted and
      assayed by polymerase chain reaction (PCR) using pan-filarial primers and various
      species-specific primers. Dog owners were interviewed using a structured
      questionnaire designed to collect information on factors that may impact the
      occurrence of filarial infection. The association between canine dirofilariasis
      prevalence and factors likely to impact infection was determined by univariate
      logistic regression analysis, followed by multivariate binomial logistic
      regression analysis. Indoor and outdoor resting mosquitoes were collected from
      houses by manual aspiration. Mosquitoes were identified according to species,
      homogenized and tested by PCR for filarial nematodes. Results: A total of 84 (8%)
      dogs were positive for D. immitis DNA, while 3 (0.3%) dogs contained
      Acanthocheilonema reconditum DNA. Several factors were significantly associated
      with D. immitis infection. For example, dogs that lived <100 m from a large
      source of open standing water were significantly more likely (p = 0.002) to
      become infected with D. immitis than other dogs. Additionally, dogs with
      infrequent or no anthelmintic treatment were significantly more likely (p = 0.0)
      to become infected than dogs that were regularly treated. The entomologic
      investigation yielded 2618 female mosquitoes from 14 species. Four pools of Culex
      quinquefasciatus were positive for D. immitis DNA and the minimum infection rate,
      calculated as the number of positive pools per 1000 mosquitoes tested, was 2.9.
      Interpretation & conclusion: The study identified several factors positively
      associated with an increased risk of D. immitis infection in domestic dogs in
      Tabasco and provides evidence that Cx. quinquefasciatus is potentially an
      important vector in this region. This information can be used by local
      veterinarians and dog owners to reduce the burden of D. immitis on canine health.

PMID- 30280715
TI  - Nontoxic water soluble nanocarbons prevent respiration of mosquito larvae,
      causing anoxia.

PMID- 30280716
TI  - Diagnostic validation of IgM and IgG ELISA and real-time PCR in detecting scrub
      typhus infection in endemic regions.

PMID- 30280717
TI  - Circulation of all dengue virus serotypes during dengue outbreak in Sandakan,
      Sabah, Malaysia (2016).

PMID- 30280718
TI  - Disseminated microinfarctions of the right kidney requiring nephrectomy: an
      unusual complication of acquired hemophilia A.

PMID- 30280719
TI  - Primary Cultivation and Identification of Vascular Smooth Muscle Cells from the
      Spiral Modiolar Artery of Guinea Pigs.
AB  - BACKGROUND This article reports a method to obtain vascular smooth muscle cells
      (SMCs) from the spiral modiolar artery (SMA) of guinea pigs and provides
      materials for related experimental studies. MATERIAL AND METHODS SMA was
      separated from the cochlea of guinea pigs, digested with trypsin (1.25 g/L) and
      allowed to adhere in a 35-mm culture dish. The morphology of the sample was
      investigated, and the sample was identified by immunofluorescence analysis, flow
      cytometry, Western blot, and RT-PCR. Cell viability was calculated using trypan
      blue and flow cytometry. Whole-cell patch clamp was used to record the membrane
      input resistance (Rinput), reciprocal membrane input conductance (Ginput),
      membrane input capacitance (Cinput), and resting membrane potential (RP) of the
      SMCs. RESULTS Microscopy results showed that the cells had typical peak-valley
      growth pattern. The cell growth curve was similar to an S curve, and flow
      cytometry results showed that the cell apoptosis rate was less than 10%.
      Moreover, flow cytometry, immunofluorescent staining, Western blot and RT-PCR
      detected the specific and intensely positive expression of cell type-specific
      markers alpha-SM-actin, SM22alpha, calponin and desmin. Furthermore, following
      properties of the P3 and P6 cells were obtained: Rinput, 2611+/-356 and 2477+/
      338 MOmega; Ginput, 0.454+/-0.071 and 0.273+/-0.037 ns; Cinput, 17.029+/-0.917
      and 18.042+/-1.051 pF, and RP -20.602+/-1.503 and -22.192+/-1.905 mV. CONCLUSIONS
      Various highly purified SMCs were obtained from the SMA of guinea pigs. We
      provide an ideal experimental material for the study of the pathogenesis of
      diseases related to the circulation disturbances in the inner ear in vitro. The
      results can be used to evaluate the effects of drugs on vascular smooth muscle.

PMID- 30280720
TI  - [Epidemiology of invasive pneumococcal disease in Tarragona, Spain, 2012-2015:
      incidence, lethality and serotype-coverage for distinct antipneumococcal vaccine
      formulations].
AB  - OBJECTIVE: Nowadays, after licensure of the second generation new pneumococcal
      conjugate vaccines (PCV10/PCV13). The epidemiology of the pneumococcal disease
      must be re-evaluated. The present study described incidence, lethality and
      serotype distribution of invasive pneumococcal disease (IPD) in the general
      population of Tarragona's region (Spain) after licensure of these vaccines.
      METHODS: Retrospective study that included all cases of IPD (pneumococcus
      isolated in sterile sites) diagnosed among all-age individuals in the Spanish
      region of Tarragona (Tarragones, Alt Camp and Baix Penedes counties) from
      01/01/2012 to 31/12/2015. Incidence and lethality rates were estimated by age
      strata and globally. Similarly, it was determined the prevalence of IPD cases
      caused by serotypes included in the distinct formulations of multivalent
      conjugate vaccines (pcv7), PCV10 and PCV13) or 23-valent polysaccharide vaccine
      (PPV23). RESULTS: A total of 171 IPD cases were observed, which means a global
      incidence (per 100,000 persons-year) of 10.82 (7.86 in <=14 years, 5.94 in 15-64
      years and 36.46 in >=65 years; p<0.001). Overall lethality rate was 6.8% (none in
      children, 9,3% in people 15-64 years and 6.9% in people >=65 years). A serotype
      was identified in 132 (77.2%) of the 171 studied samples. Serotype-vaccine
      coverages (cases due to vaccine-type serotypes) were 14.4%, 26.5%, 42.4% and
      78.8% for the PCV7, PCV10, PCV13 and PPV23, respectively (p<0.001). CONCLUSIONS:
      Incidence and lethality of IPD were intermediate-low in the region of Tarragona
      throughout 2012-2015. During this period, Serotype- vaccine coverage was almost
      double for the 23-valent than for the 13-valent vaccine.

PMID- 30280721
TI  - Evaluation of a novel cloud-based software platform for structured experiment
      design and linked data analytics.
AB  - Open data in science requires precise definition of experimental procedures used
      in data generation, but traditional practices for sharing protocols and data
      cannot provide the required data contextualization. Here, we explore
      implementation, in an academic research setting, of a novel cloud-based software
      system designed to address this challenge. The software supports systematic
      definition of experimental procedures as visual processes, acquisition and
      analysis of primary data, and linking of data and procedures in machine
      computable form. The software was tested on a set of quantitative microbial
      physiology experiments. Though time-intensive, definition of experimental
      procedures in the software enabled much more precise, unambiguous definitions of
      experiments than conventional protocols. Once defined, processes were easily
      reusable and composable into more complex experimental flows. Automatic coupling
      of process definitions to experimental data enables immediate identification of
      correlations between procedural details, intended and unintended experimental
      perturbations, and experimental outcomes. Software-based experiment descriptions
      could ultimately replace terse and ambiguous 'Materials and Methods' sections in
      scientific journals, thus promoting reproducibility and reusability of published
      studies.

PMID- 30280722
TI  - Ratiometric red-emission fluorescence detection of Al3+ in pure aqueous solution
      and live cells by a fluorescent peptidyl probe using aggregation-induced
      emission.
AB  - The development of a fluorescence method for the selective ratiometric detection
      of Al3+ ions in pure aqueous solutions and live cells is still a significant
      challenge. In the present study, we synthesized a new type of fluorescent probe
      using an Al3+-triggered self-assembly based on the dipeptide receptor and an
      aggregation-induced emission fluorophore. The fluorescent probe (1) bearing
      cyanostilbene with excitation by visible light detected Al3+ ions sensitively in
      pure aqueous buffered solution by ratiometric red-emission at 600 nm. 1 provided
      a highly selective ratiometric detection of Al3+ among 16 metal ions in aqueous
      solution. 1 exhibited sensitive ratiometric response to Al3+ in aqueous buffered
      solutions at pH ranging from 5 to 7.4. The detection limit (145 nM, R2 = 0.999)
      for Al3+ ions in pure aqueous solution was much lower than the maximum allowable
      level of Al3+ in drinking water demanded by the Environmental Protection Agency
      (EPA). The probe provided an efficient approach to detect low concentrations of
      Al3+ in ground water, tap water, and live cells by ratiometric red-emissions at
      600 nm. The binding study using dynamic light scattering, NMR, IR, and TEM
      revealed that the complex between 1 and Al3+ self-assembled to form
      nanoparticles, resulting in the enhancement of the emission at 600 nm and a
      concomitant decrease in the emission at 535 nm.

PMID- 30280723
TI  - Human-level blood cell counting on lens-free shadow images exploiting deep neural
      networks.
AB  - In point-of-care testing, in-line holographic microscopes paved the way for
      realizing portable cell counting systems at marginal cost. To maximize their
      accuracy, it is critically important to reliably count the number of cells even
      in noisy blood images overcoming various problems due to out-of-focus blurry
      cells and background brightness variations. However, previous studies could
      detect cells only on clean images while they failed to accurately distinguish
      blurry cells from background noises. To address this problem, we present a human
      level blood cell counting system by synergistically integrating the methods of
      normalized cross-correlation (NCC) and a convolutional neural network (CNN). Our
      comprehensive performance evaluation demonstrates that the proposed system
      achieves the highest level of accuracy (96.7-98.4%) for any kinds of blood cells
      on a lens-free shadow image while others suffer from significant accuracy
      degradations (12.9-38.9%) when detecting blurry cells. Moreover, it outperforms
      others by up to 36.8% in accurately analyzing noisy blood images and is 24.0
      40.8* faster, thus maximizing both accuracy and computational efficiency.

PMID- 30280724
TI  - Graphene-based nanoplatforms for surface-enhanced Raman scattering sensing.
AB  - Surface-enhanced Raman scattering (SERS) is one of the important techniques for
      sensing applications in biological analysis, disease diagnosis, environmental
      science, and food safety. Graphene provides an excellent nanoplatform for SERS
      sensing due to its two-dimensional flat structure, uniform electronic and
      photonic properties, excellent mechanical stability, atomic uniformity, and high
      biocompatibility. In this review, we summarize recent advances in the fabrication
      of various graphene-based nanoplatforms for SERS sensing. We present the
      strategies, such as self-assembly, in situ synthesis, one-pot synthesis, liquid
      phase reduction, and biomimetic synthesis, for the fabrication of graphene-based
      hybrid metallic and alloy nanoplatforms, and then demonstrate the potential
      applications of graphene-based nanoplatforms for the SERS sensing of ions,
      organic dyes, pesticides, bacteria, DNA, proteins, cells, and other chemicals in
      great detail. In addition, we also discuss the future development of this
      interesting research field and provide several perspectives. This work will be
      helpful for readers to understand the fabrication and sensing mechanisms of
      graphene-based SERS sensing nanoplatforms; meanwhile, it will promote the
      development of new materials and novel methods for high performance sensing and
      biosensing applications.

PMID- 30280725
TI  - Hierarchically porous UiO-66: facile synthesis, characterization and application.
AB  - Hierarchically porous UiO-66 (HP-UiO-66) with a particle size of ~5 nm was
      synthesized without the use of modulating reagents. The HP-UiO-66 material
      exhibits good thermal and structural stability, and shows excellent performance
      in uptaking large molecules and catalyzing the acetalization reaction of
      furfural.

PMID- 30280726
TI  - Edge-on adsorption of multi-chain functional alkanes stabilizes noncovalent
      monolayers on MoS2.
AB  - Modified long-chain alkanes are often used to functionalize graphene and MoS2
      noncovalently, with the goal of controlling the substrate electronic structure or
      interactions with the environment. Alkyl chain adsorption enthalpy is lower on
      MoS2 than on graphite; the decreased molecule-substrate interaction strength
      suggests utility for monolayer structures that increase stability through other
      means. Previously, we have found that diyne phospholipid monolayers on HOPG are
      more stable toward solution processing than monolayers of single-chain
      amphiphiles. Here, we show that this is also true for assembly on MoS2, but that
      the additional stability appears to arise from edge-on adsorption, producing
      monolayers in which alkyl chains form two stacked layers on the substrate.

PMID- 30280727
TI  - Heavy pnictogen chalcohalides: the synthesis, structure and properties of these
      rediscovered semiconductors.
AB  - This review focuses on the synthesis, properties and selected applications of
      heavy pnictogen chalcohalides, i.e. compounds of the MQX stoichiometry, where M =
      As, Sb, and Bi; Q = O, S, Se, and Te; and X = F, Cl, Br and I. The first section
      focuses on their synthesis and crystal structures, and the second section
      discusses the electronic structure on the basis of quantum chemical modelling and
      selected experimental data. Finally, the third section discusses their
      electrical, photoelectrochemical and photocatalytic properties and applications.
      In contrast to perovskites, chalcopyrites and kesterites, chalcohalides have
      attracted relatively less attention, but their structure and properties are well
      suited for numerous applications.

PMID- 30280728
TI  - Multilayer sensing platform: gold nanoparticles/prussian blue decorated graphite
      paper for NADH and H2O2 detection.
AB  - In this study, an exfoliated graphite paper (EGP) was employed as a supported
      electrode for prussian blue (PB) and gold nanoparticles (AuNPs) modification to
      fabricate a novel electrochemical sensor. The scanning electron microscopy image
      showed the multilayer structure of the sensor with PB and AuNPs uniform coating.
      Due to the high surface area and good conductivity of the multilayer structure,
      as well as the conductivity of AuNPs, the prepared sensor exhibited an obvious
      improvement for sensitive detection of nicotinamide adenine dinucleotide (NADH)
      with a linear range of 5.0 * 10-7 mol L-1-1.0 * 10-3 mol L-1. Moreover, the
      modified PB film endowed the sensor with good electrocatalytic activity for
      hydrogen peroxide (H2O2) sensing. Under the optimal conditions, the linear range
      and limit of detection for H2O2 sensitive detection were 5.0 * 10-8 mol L-1-1.0 *
      10-3 mol L-1 and 4.8 * 10-9 mol L-1, respectively. The sensor can also be used
      for detection in real samples with satisfactory results. The advantages of low
      cost, easy modification, multilayer structure, and good conductivity made the EGP
      an alternative candidate for supported electrode materials in the preparation and
      application of various electrochemical sensors.

PMID- 30280729
TI  - A one-step structure-switching electrochemical sensor for transcription factor
      detection enhanced with synergistic catalysis of PtNi@MIL-101 and Exo III
      assisted cycling amplification.
AB  - Inspired by MOFs themselves as unique matrices and electrocatalysts, we present a
      surprising discovery that rare PtNi@MIL-101 exhibits excellent synergistic
      catalysis for methylene blue. Using PtNi@MIL-101 as an efficient electrocatalyst,
      a one-step structure-switching electrochemical sensor for transcription factor
      detection has been developed for the first time.

PMID- 30280730
TI  - A fluoride ion-mediated continuous etching-redeposition strategy to synthesize Si
      nanocomposites with appropriate SiO2 coating layers for Li-ion batteries.
AB  - Silicon nanocomposites with surface coating have been promising candidates for
      high-performance anodes in Li-ion batteries. Here we report a simple yet
      effective way to synthesize Si@SiO2 nanocomposites with amorphous SiO2 coating
      through a fluoride ion-mediated continuous etching-redeposition process. The
      Si@SiO2 nanocomposite anode exhibits significantly improved lithium storage
      properties, with a reversible capacity of 1356 mA h g-1 at 2.1 A g-1 for 300
      cycles.

PMID- 30280731
TI  - A novel electrochemical immunoassay for carcinoembryonic antigen based on glucose
      oxidase-encapsulated nanogold hollow spheres with a pH meter readout.
AB  - A portable electrochemical immunosensing protocol was designed for the sensitive
      detection of a disease-related tumor biomarker (carcinoembryonic antigen, CEA,
      used in this case) on a pH meter using glucose oxidase (GOx)-encapsulated gold
      hollow microspheres (AuHMs) for signal amplification. The assay was carried out
      on a monoclonal anti-CEA capture antibody-coated microplate with a sandwich-type
      reaction mode. The GOx-entrapped AuHM was first synthesized using the reverse
      micelle method and then used as the signal-generation tag for the labeling of
      polyclonal anti-CEA detection antibody. Accompanying the formation of the
      sandwiched immunocomplexes, the loaded GOx molecules in the microsphere could
      catalyze glucose into gluconic acid and hydrogen peroxide. The as-produced
      gluconic acid changed the microenvironment of the detection solution, thus
      resulting in the shift of the pH value, which could be quantitatively determined
      on a portable pH meter. The use of gold hollow microspheres was expected to
      enhance the loaded amount of GOx for signal amplification. Two labeling protocols
      including GOx-labeled secondary antibody and GOx-AuHM-labeled secondary antibody
      were investigated for CEA detection, and improved analytical features were
      acquired with GOx-AuHM labeling. With the GOx-AuHM labeling strategy, the pH
      meter-based immunosensing device exhibited a good analytical performance for CEA
      detection within the dynamic linear range of 0.1-100 ng mL-1 at a detection limit
      of 0.062 ng mL-1. The strong attachment of anti-CEA antibodies to GOx-AuHM
      brought a good repeatability and intermediate precision down to 10%. Importantly,
      no significant differences at the 0.05 significance level were encountered in the
      analysis of 12 human serum specimens between the developed immunoassay and the
      commercialized electrochemiluminescent method for CEA determination.

PMID- 30280732
TI  - Exonuclease III-assisted multiple cycle amplification for the sensitive detection
      of DNA with zero background signal.
AB  - Detection of low-abundant DNA is essential for disease diagnosis and treatment.
      DNA polymerase-based amplification is frequently used due to its excellent
      sensitivity, but it suffers from time-consuming and labour-intensive procedures,
      complex template/primer design, and inherent nonspecific amplification.
      Alternatively, Exonuclease III (Exo III)-assisted target recycling provides a new
      approach for DNA assay because of its simplicity and general applicability, but
      it suffers from high background signal due to the nonspecific Exo III digestion
      and poor sensitivity due to single cycle signal amplification. Herein, we
      demonstrate the development of Exo III-assisted multiple cycle amplification
      (exonuclease chain reaction) for the sensitive detection of DNA with zero
      background signal. The binding of single-stranded DNA binding protein (SSB) to
      the hairpin probes can protect them from nonspecific digestion by Exo III,
      resulting in near zero background signal. The presence of the target DNA
      initiates the Exo III-triggered multiple cycle amplification, enabling the
      achievement of high sensitivity with a detection limit of 3 fM and excellent
      selectivity with single base mismatch discrimination capability, holding great
      potential in disease diagnosis and biomedical research.

PMID- 30280733
TI  - Wheel-type heterometallic ferromagnetic clusters: [Ni7-xMx(HL)6(MU3-OMe)4(MU3
      OH)2]Cl2 (M = Zn, Co, Mn; x = 1, 3).
AB  - Wheel-type heptanuclear heterometallic clusters of stoichiometry [Ni7
      xMx(HL)6(MU3-OMe)4(MU3-OH)2]Cl2 (L = 1-(2-hydroxy-3-methoxybenzamido)-2
      (benzylideneamino)ethane; M = Zn2+, Co2+, Mn2+; x = 1, 3) were synthesized, and
      their metal ion dependent ferromagnetic properties were investigated. It was
      demonstrated that the central position of each cluster was occupied by a Ni2+ ion
      while other metal ions (Zn2+, Co2+ or Mn2+) were accommodated in peripheral
      positions. The magnetic interactions, anisotropy and magnetization of the
      resultant clusters were all influenced by the combinations of metal ions present.

PMID- 30280734
TI  - Controllable synthesized heterostructure photocatalyst Mo2C@C/2D g-C3N4: enhanced
      catalytic performance for hydrogen production.
AB  - Photocatalysis is a promising technology which can be applied in the fields of
      energy and environment. However, low charge separation efficiency has limited its
      commercial applications. In this work, we report a route to a controllable
      synthesized visible-light-driven heterostructure photocatalyst Mo2C@C/2D g-C3N4.
      The interfacial conductivity was improved by introducing Mo2C@C, which promoted
      the transportation of photogenerated carriers and suppressed their recombination.
      The optimal composite achieved a hydrogen (H2) generation rate of 2269.47 MUmol g
      1 h-1, and an external quantum efficiency (EQE) achieved 9.07% at lambda = 405
      nm. Thus, the great co-catalytic activity of Mo2C@C was unambiguously
      demonstrated.

PMID- 30280735
TI  - Protein-protein interactions in trans-AT polyketide synthases.
AB  - Covering: up to 2018 The construction of polyketide natural products by type I
      modular polyketide synthases (PKSs) requires the coordinated action of several
      protein subunits to ensure biosynthetic fidelity. This is particularly the case
      for trans-AT PKSs, which in contrast to most cis-AT PKSs, contain split modules
      and employ several trans-acting catalytic domains. This article summarises recent
      advances in understanding the protein-protein interactions underpinning subunit
      assembly and intra-subunit communication in such systems and highlights potential
      avenues and approaches for future research.

PMID- 30280736
TI  - A new quinoline based luminescent Zr(iv) metal-organic framework for the
      ultrasensitive recognition of 4-nitrophenol and Fe(iii) ions.
AB  - A Zr(iv) based luminescent metal-organic framework (MOF; 1) was synthesized by a
      solvothermal method using a mixture of ZrCl4, quinoline-2,6-dicarboxylic acid
      (H2QDA) ligand and trifluoroacetic acid (modulator) having a 1 : 1 : 10 molar
      ratio in N,N-dimethylformamide (DMF). For activation, the methanol-exchanged
      sample was heated under high vacuum at 120  degrees C for 1 day. Different
      techniques like X-ray powder diffraction (XRPD), thermogravimetric analysis
      (TGA), Fourier transform infrared (FT-IR) spectroscopy and energy dispersive X
      ray (EDX) analysis were applied to fully characterize 1. The activated form of 1
      (called 1') has the formula [Zr6O6(OH)2(CF3COO)2(C11H5NO4)4(H2O)4]. It exhibited
      quick response and great selectivity for the fluorimetric sensing of 4
      nitrophenol (4-NP) in acetonitrile and Fe3+ ions in water. The probe maintained
      its high selectivity for 4-NP and Fe3+ ions even in the presence of potentially
      intrusive nitroaromatics and metal ions, respectively. The detection limits for 4
      NP and Fe3+ were found to be 1.40 ppt and 0.71 ppb, respectively. These values
      are the lowest among the existing MOF probes for Fe3+ and 4-NP. The electron and
      energy transfer processes along with the electrostatic interactions of 4-NP with
      the MOF can be the possible reasons for the selectivity for 4-NP. The
      fluorescence resonance energy transfer (FRET) process can be the major reason
      behind the quenching mechanism for Fe3+ ions. The recyclability test indicates
      that 1' is a promising probe for the long-term detection of 4-NP and Fe3+ ions.

PMID- 30280741
TI  - Three microporous metal-organic frameworks assembled from dodecanuclear {NiLn}
      subunits: synthesis, structure, gas adsorption and magnetism.
AB  - Three isostructural heterometallic metal-organic frameworks (MOFs)
      {[Ln2Ni(OAc)5(HL)(L)].solvent molecules}n (H2L = 2-hydroxyimino-N-[1-(2
      pyrazinyl)ethylidene]-propanohydrazone, Ln = Dy for 1, Tb for 2 and Gd for 3)
      were solvothermally synthesized by varying rare-earth metal ions with different
      electron configurations. Their crystal structures, gas adsorption and magnetic
      behaviors were fully investigated. The three isomorphous MOFs exhibit three
      dimensional microporous frameworks with two different orientated dodecane
      metallic {NiIILnIII(HL)}6 metallomacrocycles alternately connected by {LnIII(L)}
      connectors, in which an empty one-dimensional channel decorated by the basic
      hydrazone interior is generated. Due to their LnIII-independent microporous
      nature, the activated sample of 1 as a representative example has a significant
      CO2 uptake up to 42.2 cm3 g-1 and an unusually high CO2/N2 and CO2/CH4 adsorption
      selectivity of up to 98.8 and 16.8 at 298 K and 100 kPa. Magnetically, apparent
      antiferromagnetic interactions for both 1 and 2 as well as ferromagnetic coupling
      for 3 are respectively observed at low temperature resulting from the competition
      of magnetic anisotropy and intermetallic ferromagnetic superexchange.
      Additionally, 1 with highly anisotropic DyIII spin shows slow magnetization
      relaxation under zero dc field, whereas 3 possessing isotropic GdIII ions
      displays a significant cryogenic magnetocaloric effect with a maximum entropy
      change of 26.6 J kg-1 K-1 at 3.0 K and 70 kOe. These interesting results can
      provide valuable information on gas separation-based multifunctional 3d-4f MOF
      materials.

PMID- 30280742
TI  - The suppression of CMR in Nd(Mn1-xCox)AsO0.95F0.05.
AB  - The colossal magnetoresistance (CMR) observed in the oxypnictide NdMnAsO1-xFx has
      been further investigated. The magnetotransport is dominated by magnetopolarons.
      Magnetoresistance measurements of the series Nd(Mn1-xCox)AsO0.95F0.05 show that
      doping with cobalt on the manganese site pins the magnetopolarons and suppresses
      the CMR, which is completely destroyed by x = 0.047. The chemical doping results
      in non-stoichiometric samples, with both As and O vacancies. The relationship
      between the non-stoichiometry, magnetic order, electron doping and CMR is
      explored. The Nd antiferromagnetic transition and simultaneous reorientation of
      the Mn spins into the basal plane at 23 K (TSR) is not effected by Co doping.
      However, there is a significant decrease in TN(Mn) as the antiferromagnetic
      transition is suppressed from 360 K to 300 K as x increases from 0-0.047. The
      manganese moment at 10 K is also reduced from 3.86(2)MUB to 3.21(2)MUB over the
      same doping range. This reduction in the in-plane Mn moment decreases the
      electron-electron correlations below TSR and acts to further diminish the
      magnetoresistance.

PMID- 30280743
TI  - A facile synthesis of two new IR optical perovskites based on 1,4
      diazabicyclo[2,2,2]octane with a high laser damage threshold.
AB  - The main commercial infrared nonlinear optical (IR NLO) crystals, typically,
      AgGaS2, have some inherent disadvantages, for example, low laser damage threshold
      (LDT) or relatively poor stability, which limit their wide application. Here, we
      discover two new IR optical perovskites based on 1,4-diazabicyclo[2,2,2]octane,
      namely, (H2dabco)(PbCl3)2 (1) and (H2dabco)(H2PbBr6).H2O (2). 1 and 2 crystallize
      in the noncentrosymmetric space groups P43212 and P63mc, respectively, displaying
      a broad transparent range with high transmission. Particularly, compound 2
      exhibits a moderate SHG response of 1.8 times that of KH2PO4 (KDP) at 1064 nm
      with a high laser-induced damage threshold of 328.8 MW cm-2, indicating that it
      is a new promising NLO material.

PMID- 30280744
TI  - Pyrite FeS2/C nanoparticles as an efficient bi-functional catalyst for overall
      water splitting.
AB  - Exploration and fabrication of low-cost but highly active electrocatalysts,
      alternatives to noble metals, have remained a challenge for overall water
      splitting reaction. To date, few studies have reported that the Earth-abundant
      pyrite FeS2 is catalytically active for hydrogen evolution reaction, while there
      is no study on the oxygen evolution reaction and overall water splitting reaction
      using pyrite FeS2 as an electrocatalyst. Here, we offer a facile hydrothermal
      approach for the synthesis of FeS2 nanoparticles by the reduction of FeCl3.6H2O
      with C5H10NS2Na.3H2O. The FeS2/C nanoparticles on Ni foam (NF) deliver 10 mA cm-2
      at an overpotential of 240 mV towards the oxygen evolution reaction, which is
      lower than that of IrO2. It requires 202 mV to drive the hydrogen evolution
      reaction to reach 10 mA cm-2, while long-term durability and faster charge
      transfer kinetics confirm the good hydrogen evolution reaction performance on
      FeS2/C/Ni foam. Moreover, the pyrite FeS2/C/nanoparticles on Ni foam are
      assembled as an anode and cathode in a two-electrode alkaline electrolyzer and
      show good overall water splitting efficiency with 1.72 V at 10 mA cm-2.

PMID- 30280745
TI  - Synthesis, structure, and condensed-phase reactivity of [Ag3(MU3-H)(MU3
      BH4)LPh3](BF4) (LPh = bis(diphenylphosphino)amine) with CS2.
AB  - Electrospray ionisation mass spectrometry (ESI-MS) was used to monitor the
      reaction of AgBF4, bis(diphenylphosphino)amine (dppa = (Ph2P)2NH = LPh) and NaBH4
      in acetonitrile and thereby direct the synthesis of the silver nanocluster
      [Ag3(MU3-H)(MU3-BH4)LPh3](BF4), 3b.BF4, formed via reaction of AgBF4,
      bis(diphenylphosphino)amine (dppa = (Ph2P)2NH = LPh) and NaBH4 in acetonitrile.
      The X-ray structure of 3b.BF4 highlights that the cation adopts a planar
      trinuclear Ag3 geometry surrounded by three dppa ligands and coordinated on the
      bottom face by a MU3-hydride and on the top face by a MU3-BH4. The solution phase
      structure of 3b.BF4 was characterised by multinuclear NMR and DOSY NMR, which
      showed that the borohydride anion remains bound in the [Ag3(MU3-H)(MU3-BH4)LPh3]+
      cluster cation in solution. ESI-MS and in situ1H and HSQC NMR spectroscopy
      reveals that 3b.BF4 reacts with CS2 in solution at the BH4 site to yield
      [Ag3(H)(S2CH)LPh3]+, 4b, which has to date eluded structural characterisation via
      X-ray crystallography due to lack of formation of suitable crystals. The gas
      phase ion chemistry of [Ag3(H)(S2CH)LPh3]+ was examined under multistage mass
      spectrometry conditions using collision-induced dissociation (CID) and compared
      to that of the previously examined copper analogue, [Cu3(H)(S2CH)LPh3]+. While
      both cluster cations fragment via ligand loss, the CID spectra of the resultant
      [M3(H)(S2CH)LPh2]+ are different. Unlike [Cu3(H)(S2CH)LPh2]+, which solely
      undergoes loss of thioformaldehyde to give [Cu3(S)LPh2]+, [Ag3(H)(S2CH)LPh2]+
      gives a richer CID spectrum with fragmentation channels that include ligand loss,
      CH2S loss and reductive elimination of dithioformic acid. DFT calculations
      exploring rearrangement and fragmentation of the model systems [M3(H)(S2CH)LMe2]+
      ((Me2P)2NH = dmpa = LMe) were used to suggest plausible mechanisms and examine
      the energetics of the three competing channels: ligand loss, CH2S loss and
      reductive elimination of dithioformic acid.

PMID- 30280746
TI  - The synergistic effect of layered double hydroxides with other flame retardant
      additives for polymer nanocomposites: a critical review.
AB  - Layered double hydroxides (LDHs) are a new type of inorganic flame retardant
      additive for polymer nanocomposites. Although their unique structural properties
      and tunable chemical compositions make them highly promising, it has been noticed
      that on their own, LDHs can hardly fulfill all the requirements for commercial
      applications. In recent years, the application of LDHs together with other
      synergistic additives has been proposed as a new route for obtaining highly
      efficient flame retardant polymer nanocomposites. It is believed that the
      synergistic additives can overcome the shortcomings of LDHs. As great progress
      has been made in this field so far, we believe that a timely review is warranted.
      Thus, in this contribution, the synergistic effect of LDHs with other flame
      retardant additives including (1) phosphorus-containing compounds, (2) graphene
      and carbon compounds, (3) intumescent flame retardants, (4) magnesium hydroxide,
      (5) borate-containing compounds, and (6) some other flame retardant compounds
      will be critically reviewed. For each type of additive, the synergistic mechanism
      with LDHs, and their performance on both flame retardancy and thermal stability
      will be discussed. We believe that this work will inspire and guide researchers
      from a wide range of backgrounds and help to pave the way for major breakthroughs
      in both fundamental studies and industrial applications in this field.

PMID- 30280748
TI  - Leveraging plant exine capsules as pH-responsive delivery vehicles for
      hydrophobic nutraceutical encapsulation.
AB  - Plant exine capsules are natural microscale capsules that are highly physically
      robust and chemically resilient. They are extracted from pollen grains and plant
      spores, and can be used as renewable and safe microcapsules for encapsulation
      applications. Herein, we report the successful evacuation of natural sunflower
      pollen grains (SPGs) and Lycopodiastrum casuarinoides spore exine capsules (SECs)
      and investigated the effects of different loading methods on the encapsulation
      and release of nobiletin, a model hydrophobic nutraceutical. The compositional
      and morphological characterizations of SPGs and SECs obtained by the developed
      extraction protocol confirmed that the inside contents had been removed and
      hollow pollen cavities were obtained successfully. In addition, coumarin-6, a
      hydrophobic fluorescent probe, was encapsulated into SPGs and SECs, which proved
      the possibility of using them to encapsulate hydrophobic nutraceuticals.
      Furthermore, controlled release in simulated digestive fluids (SDF) was achieved
      by coating calcium alginate onto the outside of the SPGs and SECs. Looking
      forward, this may provide an effective and potential delivery model to protect
      loads from degradation in the stomach and achieve pH-responsive delivery of
      hydrophobic nutraceuticals after oral administration.

PMID- 30280749
TI  - Reactions of dicobalt octacarbonyl with dinucleating and mononucleating
      bis(imino)pyridine ligands.
AB  - This work focuses on the application of dicobalt octacarbonyl (Co2(CO)8) as a
      metal precursor in the chemistry of formally low-valent cobalt with redox-active
      bis(imino)pyridine [NNN] ligands. The reactions of both mononucleating mesityl
      substituted bis(aldimino)pyridine (L1) and dinucleating macrocyclic xanthene
      bridged di(bis(aldimino)pyridine) (L2) with Co2(CO)8 were investigated.
      Independent of the metal-to-ligand ratio (1 : 1 or 1 : 2 ligand to Co2(CO)8), the
      reaction of the dinucleating ligand L2 with Co2(CO)8 produces a tetranuclear
      complex [Co4(L2)(CO)10] featuring two discrete [Co2[NNN](CO)5] units. In
      contrast, a related mononucleating bis(aldimino)pyridine ligand, L1, produces
      different species at different ligand to Co2(CO)8 ratios, including dinuclear
      [Co2(CO)5(L1)] and zwitterionic [Co(L1)2][Co(CO)4]. Interestingly,
      [Co4(L2)(CO)10] features metal-metal bonds, and no bridging carbonyls, whereas
      [Co2(CO)5(L1)] contains cobalt centers bridged by one or two carbonyl ligands. In
      either case, treatment with excess acetonitrile leads to disproportionation to
      the zwitterionic [Co[NNN](NCMe)2][Co(CO)4] units. The electronic structures of
      the complexes described above were studied with density functional theory. All
      the obtained bis(imino)pyridine complexes serve as catalysts for
      cyclotrimerization of methyl propiolate, albeit their reactivity is inferior
      compared with Co2(CO)8.

PMID- 30280750
TI  - Enhanced charge extraction with all-carbon electrodes for inorganic CsPbBr3
      perovskite solar cells.
AB  - Perovskite-structured cesium lead bromide (CsPbBr3) halide provides new
      opportunities for promoting the commercialization of perovskite solar cells (PSC)
      due to its high carrier mobility and light absorption coefficient as well as
      remarkable environmental stability at high humidity and high temperatures.
      Herein, all-carbon electrodes from multi-walled carbon nanotubes (MWCNT) and
      carbon black (CB) were prepared for all-inorganic CsPbBr3 PSCs with the
      configuration of FTO/c-TiO2/m-TiO2/CsPbBr3/carbon. The as-prepared electrodes
      were free of hole-transporting layers and precious metals. The work function and
      electrical conductivity of the carbon electrode were tuned by changing the
      MWCNT/CB ratio to reduce charge recombination at the perovskite/carbon interface.
      The optimal all-inorganic PSC achieves a maximum power conversion efficiency of
      7.62% using the MWCNT (75 wt%)/CB (25 wt%) electrode in comparison with 6.24% for
      the pure MWCNT-based device. Upon persistent attack by 80% RH in air atmosphere,
      the solar cell retains 95% of its initial efficiency over 1100 h.

PMID- 30280751
TI  - Differential responses of endothelial integrity upon the intake of
      microencapsulated garlic, tomato extract or a mixture: a single-intake,
      randomized, double-blind, placebo-controlled crossover trial.
AB  - This study investigated the effect of microencapsulated garlic and/or tomato on
      endothelial dysfunction induced by the PhenFlex test (PFT) in healthy male
      smokers. In a randomized, double-blind, placebo-controlled crossover trial, 41
      healthy male smokers were randomly assigned to one of four groups to receive the
      test groups (in microencapsulated garlic powder, tomato extract and a mixture
      thereof) or the placebo group. Proteomic biomarkers related to endothelial
      integrity were measured in plasma. Microencapsulated garlic, tomato extract and
      the mixture affected endothelial integrity biomarkers differently. Garlic
      consumption increased prothrombin time and decreased SAA and IL-12. Tomato
      extract intake increased activated partial thrombin time and decreased d-dimer,
      SAA, sVCAM-1, IL-13 and MCP-3 levels. Consumption of the mixture increased sE
      selectin and lowered D-dimer, SAA, IL-13 and IL-10 responses after PFT challenge
      for 6 h. The different responses became clearer under high compliance in the
      dietary restriction groups. This single-intake clinical trial addressed the
      different responses of biomarkers related to endothelial integrity.

PMID- 30280752
TI  - Comment on: Omega-3 polyunsaturated fatty acid inhibits the malignant progression
      of hepatocarcinoma by inhibiting the Wnt/beta-catenin pathway.

PMID- 30280753
TI  - MiR-340-5p is a potential prognostic indicator of colorectal cancer and modulates
      ANXA3. It is a cost-effective genetic test.

PMID- 30280754
TI  - Neurodegenerative disorders, gut human microbiome and diet: future research for
      prevention and supportive therapies.

PMID- 30280755
TI  - Microbiome and bariatric surgery: new options to precision surgery.

PMID- 30280756
TI  - Relationship between oral microbiota and periodontal disease: a systematic
      review.
AB  - OBJECTIVE: In recent years metagenomic analysis has become more accessible for
      the characterization of biological specimens. There has been an important
      increase of studies using this technique for subgingival human samples. To date,
      there are no updated systematic reviews on the relationship between oral
      microbiota and periodontal disease. The aim of the present systematic review was
      to update data about studies concerning the influences of changes in oral
      microbiota composition on the periodontal status in human subjects. MATERIALS AND
      METHODS: An electronic search was conducted in four databases (MEDLINE, Scopus,
      CENTRAL and Web of Science) for articles published in English from January 2014
      to April 2018. In vitro or animal studies, case reports, case series,
      retrospective studies, review articles, abstracts and discussions were excluded.
      Also, studies that evaluated less than 5 microbial species, only viruses or
      already known periodontal pathogens were excluded. Two independent researches
      selected the studies and extracted the data. The quality of evidence was assessed
      as high, moderate or low for each microorganism. RESULTS: Eight studies and three
      additional publications recovered from the bibliography search of the selected
      articles were included in the review. The Bacteria domain was the main detected
      among the others and it included 53 species. The review confirmed the presence of
      recognized periodontal pathogens such as the members of the red complex but also
      identified, with high weight of evidence, the presence of new pathogens.
      CONCLUSIONS: The results of this systematic review support high evidence for the
      association of 3 new species/genera with the etiology of periodontitis. Future
      investigations on the actual role of these new pathogens in the onset and
      progression of the disease are needed.

PMID- 30280757
TI  - p38-MAPK pathway is activated in retinopathy of microvascular disease of STZ
      induced diabetic rat model.
AB  - OBJECTIVE: To investigate the role of corticotropin releasing hormone (CRH) in
      diabetic retinopathy of microvascular disease and the potential mechanism.
      MATERIALS AND METHODS: The diabetic rat model was constructed by a single
      intraperitoneal injection of streptozotocin (STZ). The expression of CRH in the
      retina of diabetic rats and wild-type rats was detected by Real-Time Polymerase
      Chain Reaction (RT-PCR). CRH shRNA or Scr shRNA adenovirus was injected into the
      eyes of diabetic rats and wild-type rats, respectively. The effect of down
      regulated CRH on visual electrophysiology in rats was evaluated. Protein
      expressions of vascular endothelial growth factor (VEGF) and inflammatory factors
      that were related to the microvascular lesion after CRH downregulation were
      detected by Western blot. Furthermore, p38 expression was detected by Western
      blot to explore whether mitogen-activated protein kinase (MAPK) signaling pathway
      was involved in the function of retinal endothelial cells regulated by CRH.
      RESULTS: The expression of CRH was significantly up-regulated in the retina of
      diabetic rats. RT-PCR results showed that the mRNA level of CRH in the retina of
      diabetic rats injected with CRH shRNA was decreased. However, no significant
      change in CRH level was observed in rats injected with Scr shRNA adenovirus. The
      down-regulated CRH could improve the diabetes-induced visual impairment and
      retinal inflammatory response. Moreover, the down-regulated CRH led to a
      decreased phosphorylation level of p38. CONCLUSIONS: CRH improves the diabetic
      retinopathy of microvascular disease via the p38-MAPK pathway, which is expected
      to be a new target for the treatment of diabetic microangiopathy.

PMID- 30280758
TI  - Hsa-miR-203 inhibits fracture healing via targeting PBOV1.
AB  - OBJECTIVE: To explore the role of hsa-miR-203 in fracture healing and its
      underlying mechanism. PATIENTS AND METHODS: Expression levels of hsa-miR-203 and
      PBOV1 in patients with hand fractures and intra-articular fractures after
      treatment were detected by quantitative Real-Time-Polymerase Chain Reaction (qRT
      PCR). Viability and apoptosis of osteoblast cell line hFOB1.19 after hsa-miR-203
      overexpression or knockdown were detected by cell counting kit-8 (CCK-8) assay
      and flow cytometry, respectively. The target gene of hsa-miR-203 was predicted by
      bioinformatics and verified by dual-luciferase reporter gene assay. Rescue
      experiments were conducted to further verify whether hsa-miR-203 could
      participate in fracture healing via PBOV1. RESULTS: No significant hsa-miR-203
      expression was found in patients with hand fractures and intra-articular
      fractures after treatment for 7 days, which was remarkably upregulated on the
      14th day. PBOV1 expression was gradually downregulated as treatment time
      prolongation. Overexpression of hsa-miR-203 decreased cell viability, but induced
      apoptosis of hFOB1.19 cells. Bioinformatics predicted that PBOV1 might be the
      target gene of hsa-miR-203, which was further verified by dual-luciferase
      reporter gene assay. The effect of hsa-miR-203 on viability and apoptosis of
      hFOB1.19 cells was reversed after the PBOV1 knockdown. CONCLUSIONS: Hsa-miR-203
      inhibits fracture healing by regulating osteoblast viability and apoptosis via
      targeting PBOV1.

PMID- 30280759
TI  - MiR-203 is essential for the shift from osteogenic differentiation to adipogenic
      differentiation of mesenchymal stem cells in postmenopausal osteoporosis.
AB  - OBJECTIVE: The purpose of this study was to investigate how miR-203 promotes
      osteogenic differentiation of bone marrow mesenchymal cells (BMSCs) by regulating
      its target gene DKK1, thereby inhibiting the occurrence of osteoporosis. PATIENTS
      AND METHODS: A total of 60 cases with postmenopausal osteoporosis and 40 cases of
      normal individuals were recruited. The expression of miR-203 in serum of all
      cases was detected by quantitative reverse transcriptase-polymerase chain
      reaction (qRT-PCR). The capacity of osteogenesis and adipogenic differentiation
      of MSCs was determined by alizarin red staining and oil red staining,
      respectively. Transfection of miR-203 mimics and miR-203 inhibitor were mediated
      by Liposomes, and then the MSCs were induced osteogenic and adipogenic
      differentiation. MiR-203 mimic was co-transfected with wild-type or mutant DKK1
      for luciferase reporter gene detection. In the osteoporosis model of rats, the
      tibia was taken for micro-CT examination of bone mineral density (BMD) and bone
      volume/structural parameters (BV/TV), while the femur was taken for the
      measurement of absorption parameters (Ob.S)./BS) and the number of osteoclasts
      per circumference of bone (N.Oc/B.Pm). RESULTS: The expression level of miR-203
      was significantly lower in patients with postmenopausal osteoporosis than that in
      normal individuals. The osteogenic capacity of BMSCs in these patients was
      reduced, while their adipogenic capacity was enhanced. MiR-203 promoted the
      expression of osteogenic genes and inhibited that of adipogenic genes. Knockdown
      of miR-203 decreased the level of osteogenic related genes but increased that of
      adipogenic related genes, while overexpression of miR-203 led to the opposite
      results. Furthermore, miR-203 inhibited the protein expression of DKK1. In
      addition, bone density and bone volume/structural parameters were lower in
      ovariectomized rats than those in normal rats. Meanwhile, bone resorption
      parameters and the number of osteoclasts per bone circumference in ovariectomized
      rats were higher than those in normal rats. CONCLUSIONS: MiR-203 can promote
      osteogenic differentiation of mesenchymal stem cells by downregulating the gene
      expression of DKK1.

PMID- 30280760
TI  - CRNDE impacts the proliferation of osteoclast by estrogen deficiency in
      postmenopausal osteoporosis.
AB  - OBJECTIVE: Bone loss is the main reason for postmenopausal osteoporosis, caused
      by estrogen deficiency. ERT (estrogen replacement therapy) has been demonstrated
      to protect bone loss efficiently. LncRNA (long non-coding RNA) has been proved to
      be important in different disease progression. We aimed at analyzing whether the
      lncRNAs influence the activity of osteoclasts and the progression of this
      disease. PATIENTS AND METHODS: RT-PCR (reverse transcriptase-polymerase chain
      reaction) was used to detect the expression of lncRNA CRNDE in OH (osteoclast
      from healthy people) and OP (osteoclast from patients with postmenopausal
      osteoporosis). MTT (methylthiazolyl tetrazolium) assay was used to detect the
      viability of the cells. The cell cycle and apoptosis rate in OH and OP were
      measured by the flow cytometry analysis. Western blot was used to analyze the
      possible related mechanism that CRNDE regulated the cells proliferation in
      postmenopausal osteoporosis. RESULTS: We found that the CRNDE was highly
      expressed in the osteoclast from patients with OP, compared with OH. We also
      found that overexpressing CRNDE increased the viability in OH whilst reducing
      CRNDE in OP decreased the viability. The cell cycle was arrested in G0/G1 phase
      and the apoptosis rate was improved in OP after transfection with siRNA.
      Moreover, CRNDE could impact the proliferation of osteoclasts by PI3K/Akt
      signaling pathway and estrogen could inhibit this proliferation. CONCLUSIONS: We
      found that lncRNA CRNDE was closely related to the postmenopausal osteoporosis
      with estrogen deficiency. CRNDE may be involved in the development and
      progression of postmenopausal osteoporosis in the absence of estrogen and become
      a potential target for treating.

PMID- 30280761
TI  - The impact of collagen sponge composite bone marrow mesenchymal stem cells
      (BMSCs) in inducing interbody fusion.
AB  - OBJECTIVE: To assess the effectiveness of bone mesenchymal stem cells (BMSCs) in
      the induction of interbody fusion. PATIENTS AND METHODS: The 3rd generation BMSCs
      were seeded on collagen sponge scaffold and cultured in osteoblast induction
      medium for 3 weeks to prepare cell-scaffold complex. Thirty patients were
      randomly divided into three groups to establish the L4/L5 interbody fusion model.
      The cell-scaffold complex was implanted in the intervertebral space in group I,
      the collagen sponge scaffold was implanted in group II, and the autologous iliac
      crest spongy bone was implanted in group III. Palpation, radiography, micro-CT,
      and histology were performed on the 12th weeks after operation to evaluate
      osteogenesis and spinal fusion. RESULTS: BMSCs differentiated into osteoblasts in
      the cell-scaffold complex after osteogenic induction for 3 weeks. The spinal
      fusion rates in group I, II, and III were 40%, 0%, and 70%, respectively. Micro
      CT and histological examination showed mature bone marrow and trabecular bone
      formation in the fusion segments. The new bone was integrated with the upper and
      lower vertebral body. The bone trabecula in group III was stronger than group I.
      The surgical segments in group II was scar tissue without collagen sponge
      residue. CONCLUSIONS: BMSCs can induce osseous fusion in the lumbar vertebra.

PMID- 30280762
TI  - Targeted inhibition of beta-catenin by miR-320 and decreased MMP-13 expression in
      suppressing chondrocyte collagen degradation.
AB  - OBJECTIVE: Wnt/beta-catenin pathway plays a critical role in modulating embryonic
      development, cell growth, and differentiation. The over-expression of beta
      catenin activates this pathway and up-regulates expression of matrix
      metalloproteinase-13 (MMP-13), and promotes matrix degradation and occurrence of
      osteoarthritis (OA). This study aims to explore the effect of miR-320 expression
      in OA chondrocyte and underlying mechanisms. PATIENTS AND METHODS: Chondrocyte
      tissues from OA patients and normal individuals were collected for the detection
      of expression levels of miR-320, beta-catenin, MMP-13, and alpha-1 chain of type
      II collagen (COL2A1). Dual luciferase reporter assay was performed to test
      targeted regulation between miR-320 and beta-catenin. IL-1beta was used to
      simulate in vitro cultured chondrocytes, which were transfected with miR-320
      mimic and/or si-beta-catenin, followed by quantification of miR-320, beta
      catenin, MMP-13, and COL2A1. RESULTS: In chondrocytes of OA patients, expression
      of microRNA (miR)-320 is decreased. Bioinformatics analysis revealed
      complementary binding sites between miR-320 and beta-catenin. Compared to control
      group, increasing levels of beta-catenin and MMP-13 expression with reduction of
      miR-320 and COL2A1 expressions were observed in OA chondrocytes. Transfection of
      miR-320 mimic and/or si-beta-catenin depressed expression of beta-catenin and MMP
      13 inside chondrocytes, accompanied with elevation of COL2A1 expression.
      CONCLUSIONS: MiR-320 expression in OA chondrocyte is decreased, accompanied with
      up regulation of beta-catenin and MMP-13. MiR-320 can inhibit beta-catenin and
      MMP-13 expressions, elevates COL2A1 expression, which provides novel insights for
      the treatment of osteoarthritis.

PMID- 30280763
TI  - The down-regulation of long non-coding RNA LINC01088 is associated with the poor
      prognosis of epithelial ovarian cancer patients.
AB  - OBJECTIVE: Long intergenic non-coding RNA 1088 (LINC01088) has been suggested to
      act as a tumor suppressor in epithelial ovarian cancer (EOC); however, the
      prognostic role of LINC01088 has not been evaluated in cancer patients. This
      study aimed to investigate the expression of LINC01088 in EOC, along with
      evaluating its clinical-pathological and prognostic importance. PATIENTS AND
      METHODS: A bioinformatics tool (GEPIA) was used to screen the dysregulated
      lncRNAs. Quantitative Real-time PCR (qRT-PCR) was used to measure expression
      level of LINC01088 in EOC tumor samples and adjacent non-tumor tissues. Then, the
      association between LINC01088 expression and pathological parameters were further
      evaluated. Overall survival (OS) was estimated using the Kaplan-Meier method, and
      the differences in survival were compared using the log-rank test. Univariate and
      multivariate analysis were performed using the Cox proportional hazard analysis.
      RESULTS: We found that LINC01088 expression was significantly down-regulated in
      EOC tissues via "GEPIA". Then, the results of RT-PCT confirmed that the
      expression levels of LINC01088 were significantly lower in EOC tissues compared
      to adjacent noncancerous tissues (p < 0.01). Interestingly, lower LINC01088
      expression levels were associated with FIGO stage (p = 0.000), grade (p = 0.003)
      and distant metastasis (p = 0.006). Moreover, Kaplan-Meier analysis indicated
      that patients with low LINC01088 expression had a poor overall survival (p =
      0.0013). Finally, univariate and multivariate analysis show that LINC01088
      expression is an independent predictor for overall survival. CONCLUSIONS: Low
      LINC01088 expression was associated with the progression of EOC and could serve
      as a potential independent prognostic biomarker for patients with EOC.

PMID- 30280764
TI  - miR-532-5p is a prognostic marker and suppresses cells proliferation and invasion
      by targeting TWIST1 in epithelial ovarian cancer.
AB  - OBJECTIVE: Dysregulated miR-532-5p has been observed in epithelial ovarian cancer
      (EOC). However, the potential biological function and clinical significance have
      not been fully explained. The study aimed to investigate the prognostic value and
      potential role of miR-532-5p in EOC. PATIENTS AND METHODS: MiR-532-5p and Twist
      homolog 1 (TWIST1) mRNA expression were examined using quantitative real-time
      PCR. The correlation of miR-532-5p expression with clinicopathological factors
      was statistically analyzed. Kaplan-Meier analysis and Cox proportional hazards
      regression models were explored to reveal the correlations of miR-532-5p
      expression with survival of patients. Cell Counting Kit-8, colony formation and
      transwell invasion assays were performed to evaluate the effects of miR-532-5p on
      cell proliferation and invasion, respectively. MiR-532-5p target genes were
      confirmed using luciferase activity, RT-PCR and Western blot assays. RESULTS: We
      found that miR-532-5p was significantly decreased in EOC tissue and cell lines,
      and its expression levels were highly correlated with grade (p = 0.011), FIGO
      stage (p = 0.004) and distant metastasis (p = 0.008). In addition, overall
      patient survival for those with high miR-532-5p expression was significantly
      longer than those patients with low miR-532-5p expression (p = 0.0058).
      Multivariate regression analysis identified miR-532-5p down-regulation as an
      independent unfavorable prognostic factor in EOC patients. Function assays showed
      that overexpression of miR-532-5p inhibited proliferation, colony formation and
      invasion of EOC cells. Mechanistic investigations confirmed TWIST1 as a direct
      target of miR-532-5p. Further in vitro assay indicated that restored expression
      of TWIST1 dampened miR-532-5p-mediated suppression of tumor progression.
      CONCLUSIONS: Our data suggested that miR-532-5p may act not only as a novel
      prognostic marker, but also as a potential target for molecular therapy of EOC.

PMID- 30280765
TI  - Reduced expression of miR-564 is associated with worse prognosis in patients with
      osteosarcoma.
AB  - OBJECTIVE: MiR-564 has been reported to be involved in the development of several
      types of cancers. However, its clinical significance in osteosarcoma (OS) has not
      been investigated. We aimed to explore the prognostic value of miR-564 in OS
      patients. PATIENTS AND METHODS: Quantitative RT-PCR assay was used to detect the
      expression levels of miR-564 in OS tissues and matched normal bone tissues. The
      correlation between miR-564 expression and clinicopathological features was
      analyzed by Pearson's chi2-test. The disease-free survival and overall survival
      rates of OS patients were calculated by the Kaplan-Meier method. Cox regression
      analysis was used to assess factors related to survival. RESULTS: We observed
      that the level of miR-564 was significantly reduced in OS tissues compared with
      that in the paired noncancerous bone tissues (p < 0.01). In addition, low miR-564
      expression was found to be closely correlated with advanced clinical stage (p =
      0.000) and distant metastasis (p = 0.003). Furthermore, survival analyses showed
      that patients with low expression of miR-564 had a shorter overall survival (p =
      0.001) and disease-free survival (p = 0.001) than those with high expression of
      miR-564. Finally, we showed that miR-564 was an independent poor prognostic
      factor for both 5-year overall survival (p = 0.001) and 5-year disease-free
      survival (p = 0.001) through multivariate analysis. CONCLUSIONS: Overall, our
      data for the first time suggest that downregulated miR-564 may be used as a novel
      prognosis predictor of OS.

PMID- 30280766
TI  - MiR-100 up-regulation enhanced cell autophagy and apoptosis induced by cisplatin
      in osteosarcoma by targeting mTOR.
AB  - OBJECTIVE: Mammalian target of rapamycin (mTOR) can negatively regulate cell
      autophagy, while its expression and activity are associated with the pathogenesis
      of osteosarcoma. MicroRNA 100 (MiR-100) down-regulation is associated with the
      pathogenesis and chemo-sensitivity of osteosarcoma. Bioinformatics analysis
      revealed the targeted relationship between miR-100 and the 3'-UTR of mTOR. We
      investigate the role of miR-100 in affecting mTOR expression, osteosarcoma cell
      autophagy, and sensitivity to cisplatin. PATIENTS AND METHODS: MiR-100, mTOR, and
      Beclin-1 expressions in osteosarcoma tissue and normal control were compared. The
      relationship between miR-100 and mTOR was verified by dual luciferase assay. MiR
      100, mTOR, and Beclin-1 levels in MG-63 cells and MG-63/DDP cells were tested.
      Cell apoptosis was determined by using flow cytometry. Cell malignancy was
      evaluated by colony formation assay. RESULTS: MiR-100 and Beclin-1 significantly
      declined, while mTOR significantly increased in osteosarcoma tissue compared with
      that of normal tissue (p<0.05). MiR-100 targeting significantly inhibited mTOR
      expression compared to that of untreated (p<0.05). MiR-100 expression was down
      regulated and mTOR level was elevated in MG-63/DDP cells compared with MG-63
      cells (p<0.05). MG-63/DDP cells exhibited reduced cell autophagy and apoptosis,
      and enhanced colony formation induced by DDP. MiR-100 mimic and/or small
      interfere mTOR (si-mTOR) significantly promoted Beclin-1 expression, cell
      autophagy, and cell apoptosis, while attenuated colony formation. CONCLUSIONS:
      MiR-100 declined, while mTOR up-regulated in osteosarcoma tissue. MiR-100 up
      regulation enhanced cell autophagy and apoptosis induced by cisplatin via
      targeted inhibiting of mTOR.

PMID- 30280767
TI  - LncRNA LINC00628 overexpression inhibits the growth and invasion through
      regulating PI3K/Akt signaling pathway in osteosarcoma.
AB  - OBJECTIVE: Osteosarcoma (OS) is the most common primary malignancy, mainly
      arising from the metaphysic of the long bones of adolescents and young adults.
      Although osteosarcoma has been studied widely, the underlying molecular mechanism
      remains unclear. Increasing evidence shows that abnormal long non-coding RNAs
      (LncRNAs) expression is involved in tumorigenesis. The aim of this study was to
      identify the detailed role of LncRNA LINC00628 in osteosarcoma. MATERIALS AND
      METHODS: The relative mRNA expression level of LINC00628 in adjacent tissues,
      osteosarcoma tissues with or without metastasis and osteosarcoma cell lines were
      detected by qRT-PCR. Overall survival curves for two groups defined by high and
      low expression level of LINC00628 in osteosarcoma patients. The cell
      proliferation, invasion and migration in osteosarcoma cells after transfection
      with lncRNA- NC or lncRNA-LINC00628 were detected. The cell cycle distribution
      and apoptosis rate in osteosarcoma cells after transfection with lncRNA- NC or
      lncRNA-LINC00628 were measured using the Flow cytometry analysis. The relative
      protein expression level of p-PI3K, p-Akt, P53 and Bcl-2 in osteosarcoma cells
      after transfection with lncRNA- NC or lncRNA-LINC00628 were detected by Western
      blot. RESULTS: LINC00628 expression was significantly decreased in osteosarcoma
      tissues compared with adjacent tissues. Meanwhile, osteosarcoma tissues with
      metastasis were significantly associated with a low expression level of LINC00628
      and the low expression level of LINC00628 has a lower overall survival rate.
      LINC00628 expression was increased in osteosarcoma cell lines after transfection
      with lncRNA-LINC00628 and the cell proliferation, invasion and migration in
      osteosarcoma cells after transfection with lncRNA-LINC00628 were significantly
      inhibited. Moreover, the cell cycle was arrested in G0/G1 phase and the apoptosis
      rate was increased in osteosarcoma cells after transfection with lncRNA
      LINC00628. Mechanistically, the relative protein expression level of p-PI3K, p
      Akt and Bcl-2 were significantly increased and the relative expression of P53 was
      significantly decreased in osteosarcoma cells after transfection with lncRNA
      LINC00628. CONCLUSIONS: LINC00628 expression was decreased in osteosarcoma. The
      overexpression of LINC00628 inhibited the proliferation, invasion and migration
      and promoted cell apoptosis in osteosarcoma cells through the inactivation of
      PI3K/Akt signaling pathway. This lncRNA may be involved in the development and
      progression of osteosarcoma.

PMID- 30280768
TI  - Biomarkers and new therapeutic targets in renal cell carcinoma.
AB  - OBJECTIVE: Renal Cell Carcinoma (RCC) is the most common malignancy in adult
      kidneys. The American Cancer Society estimated 62,700 new cases and 14,240 deaths
      in 2018. Although early detection has improved in recent years, the treatment
      remains a challenge and reliable biomarkers for poor outcomes become necessary
      for the prevention of metastases and improve the quality of patients' life during
      and after treatment. Then, the current status of the search for new RCC
      biomarkers was discussed, as well as the latest discoveries in the RCC risk and
      metastatic treatment were discussed in this review. MATERIALS AND METHODS:
      Extensive research was carried out in the online databases and full-free text
      articles published in the last 5 years, or more when convenient, were evaluated.
      Articles were included that addressed the proposed theme and were published in
      the English language. RESULTS: The present state of knowledge on biomarkers for
      RCC carcinogenesis and progression is still much to be understood about RCC risk
      factors and molecular pathways resulting in metastatic progression. Newest RCC
      target therapies were discussed, mainly in relation to immunological therapy, and
      vaccines that have been tested in numerous trials with different cancer types.
      CONCLUSIONS: The development of targeted therapies has revolutionized the
      treatment of advanced and metastatic cancers or non-responder patients. Combined
      therapy between classical chemotherapy and adjuvant immunotherapies has been
      modifying the cancer patients prognosis and bringing the hope of a cure in many
      cases.

PMID- 30280769
TI  - Evaluating the diagnostic and prognostic value of long non-coding RNA SNHG15 in
      pancreatic ductal adenocarcinoma.
AB  - OBJECTIVE: Long non-coding RNA SNHG15 (SNHG15) has been reported to play very
      important roles in the malignancy behaviors of various tumors, including
      pancreatic ductal adenocarcinoma (PDAC). However, its clinical significance in
      PDAC remains largely unclear. The aim of this study was to investigate whether
      the aberrant expression of SNHG15 can be used as potential prognostic and
      diagnostic markers of human PDAC. MATERIALS AND METHODS: TaqMan Real Time-PCR was
      performed to investigate the expression of SNHG15 in PDAC tissues and serum
      samples. Receiver operator characteristic (ROC) analysis was applied to obtain
      the diagnostic utility of SNHG15. Association between SNHG15 levels and
      clinicopathological factors was analyzed. Kaplan-Meier curves and multivariate
      Cox proportional models were used to study the impact on clinical outcome.
      RESULTS: SNHG15 levels were significantly up-regulated in both sera and tumors
      tissues from PDAC patients. ROC curve analysis revealed that SNHG15 may be a
      potential biomarker for differentiating PDAC tissues from normal pancreatic
      tissues, and the plasma levels of SNHG15 may be a potential biomarker for
      differentiating PDAC patients from healthy controls. Clinicopathologic analysis
      revealed that high SNHG15 expression was associated with tumor differentiation (p
      = 0.000), lymph node metastasis (p = 0.001) and tumor stage (p = 0.005).
      Furthermore, patients with high SNHG15 expression had a shorter overall survival
      compared with the low SNHG15 expression group (p = 0.003). Also, Cox multivariate
      analyses confirmed that SNHG15 expression was an independent prognostic factor in
      PDAC (p < 0.004). CONCLUSIONS: Our study firstly indicated the potential value of
      SNHG15 as an important biomarker for the diagnosis and prognosis prediction of
      PDAC.

PMID- 30280770
TI  - MicroRNA-23a induces apoptosis of hepatocarcinoma cell line MHCC97H via down
      regulating KIAP: a mechanism study.
AB  - OBJECTIVE: Hepatocarcinoma is a great threat to global health. MicroRNA-23a was
      suggested to regulate growth and apoptosis in certain cell lines. Our study was
      focused on growth, proliferation, and apoptosis of hepatocarcinoma cell line
      MHCC97H under the influence of microRNA-23a, and explored the mechanism of pro
      apoptosis microRNA-23a. MATERIALS AND METHODS: MicroRNA-23a and control microRNA
      (scramble miRNA, for short as miRNA) were synthesized with the routine protocol.
      Lipofection transfection was performed in hepatocarcinoma cell line MHCC97H. 3
      (4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay,
      caspase-3 activity detection, and flow cytometry were performed to examine
      growth, proliferation, and apoptosis of hepatocarcinoma cell line MHCC97H,
      respectively. Kidney inhibitor of apoptosis protein (KIAP) and small interfere
      RNA (siRNA) was synthesized for inhibition of KIAP. KIAP plasmid was established
      for activation of KIAP. Western blot was performed to examine the protein
      expression of KIAP and caspase protein family after transfection of KIAP siRNA or
      KIAP plasmid. RESULTS: Compared with miRNA transfection, microRNA-23a
      transfection significantly reduced the growth of MHCC97H cells, and decreased the
      expression of KIAP (p < 0.05). Enhanced translocation of phosphatidylserine and
      activation of caspase-3 were observed in microRNA-23a transfection cells.
      Moreover, inhibition of KIAP enhanced the pro-apoptosis effect of microRNA-23a,
      while activation of KIAP abrogated pro-apoptosis effect of microRNA-23a.
      CONCLUSIONS: MicroRNA-23a inhibits growth and proliferation of MHCC97H cells, and
      induces apoptosis of MHCC97H cells via down-regulating KIAP. KIAP could be a
      potential therapeutic target for hepatocarcinoma treatment.

PMID- 30280771
TI  - Expressions of HBV X gene regulated by different promoters and their effects on
      cell apoptosis.
AB  - OBJECTIVE:   To investigate the difference in expression level of hepatitis B
      virus (HBV) X gene, and to further study the difference of HBV X protein (HBx) at
      varied expression levels in apoptosis regulation of hepatocellular carcinoma
      cells. The recombinant plasmid rPX with HBV enhancer 1 (Enh1), X gene promoter, X
      gene and polyA tail were constructed, respectively. PATIENTS AND METHODS: HepG2
      cells were transiently transfected with the recombinant plasmids and control
      vector pGEM(r)-7Zf (+) by virtue of Fugene(r)HD; reverse transcription PCR (RT
      PCR) and Western blotting were applied to analyze the transcription and
      expression of HBV X gene as well as the difference in the expression level in
      multiple groups. The activity of the transfected cells in each group was detected
      by using the methyl thiazolyl tetrazolium (MTT) method for 6 consecutive days
      after transfection. A flow cytometer was utilized to measure the cell apoptosis
      rate. RESULTS: The RT-PCR results showed that messenger RNA expression of HBV X
      gene was detected in all HepG2 cells transfected by different recombinant
      plasmids, of which the relationships of the expression levels were rCX>rEX1 and
      rEX2> rPX (p<0.05). Only HepG2/rCX cells in each group of transfected cells
      showed HBx expression by Western blot. MTT method revealed that there were
      notable differences between HepG2/rCX, HepG2/rEX1, HepG2/rPX and HepG2/pGEM(r)
      7Zf (+) (p<0.05). The apoptosis rates of HepG2/rCX, HepG2/rEX1 and HepG2/rPX were
      significantly higher than that of HepG2/pGEM(r)-7Zf (+) (p<0.05). CONCLUSIONS:
      HBx can promote cell apoptosis. Results of this research also indicate that there
      is a significant difference in the pro-apoptotic role of HBx when its expression
      is regulated by different promoters, and such a difference may be a part of the
      complex pathogenic mechanisms of HBV and hepatocellular carcinoma.

PMID- 30280772
TI  - Down-regulation of miR-1236-3p is correlated with clinical progression and
      unfavorable prognosis in gastric cancer.
AB  - OBJECTIVE: MiRNAs have been considered to participate in many processes of
      various cancers, including gastric cancer (GC). However, the significance of
      miRNAs in the progression prognosis of GC is largely unknown. The goal of this
      study was to determine the expression level of miR-1236-3p in GC and its clinical
      association. PATIENTS AND METHODS: Clinical specimens from GC patients were
      obtained to quantify the expression level of miR-1236-3p using quantitative Real
      time PCR. The correlation between the miR-1236-3p levels and the
      clinicopathological factors of the GC patients was analyzed. The association
      between miR-1236-3p expression and overall survival was estimated by the Kaplan
      Meier method. The significance of different variables with respect to survival
      was analyzed using the univariate and multivariate Cox proportional hazards
      model. RESULTS: We found that miR-1236-3p was significantly downregulated in GC
      tissues compared to non-tumor gastric tissues (p < 0.01). The levels of miR-1236
      3p expression were associated significantly with clinical stage (p = 0.002),
      lymph node metastasis (p = 0.000) and distant metastasis (p = 0.017). Kaplan
      Meier survival analysis showed that patients in the high miR-1236-3p expression
      group had better overall survival than those in the low miR-1236-3p expression
      group (p = 0.0039). Moreover, we confirmed that miR-1236-3p was an independent
      poor prognostic factor for GC patients through univariate and multivariate
      analysis. CONCLUSIONS: Our findings provide evidence that miR-1236-3p expression
      is frequently decreased in GC tissues, and its low expression may be a
      significant prognostic factor for poor survival in GC patients.

PMID- 30280773
TI  - Expression and prognosis of MYOZ2 in gastric cancer.
AB  - OBJECTIVE: To investigate the expression of human myozenin 2 (MYOZ2) in cancer
      tissues and its effect on the prognosis of patients with gastric cancer. PATIENTS
      AND METHODS: Gastric cancer tissue and adjacent normal tissue specimens were
      obtained from a total of 258 patients together with complete clinicopathological
      data. Those patients were treated in Harbin Medical University Cancer Hospital
      from March 2007 to March 2012. Quantitative Real Time-Polymerase Chain Reaction
      (RT-PCR) was used to detect the expression of MYOZ2 messenger RNA (mRNA) in
      gastric cancer tissues and normal gastric tissues, and correlations between the
      expression level of MYOZ2 in gastric cancer tissues and the clinicopathological
      parameters of patients were analyzed. MYOZ2 protein expression levels in
      different gastric cancer cells were detected by Western blotting; transwell
      chamber assay was used to detect the effect of MYOZ2 expression on the in-vitro
      migration and invasion abilities of gastric cancer cells; 3-(4,5-Dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to examine the in
      vitro proliferation and growth abilities of gastric cancer cells. RESULTS: The
      expression level of MYOZ2 mRNA in gastric cancer tissues was significantly higher
      than that in cancer-adjacent tissues in 258 cases (p<0.05). Western blotting
      results showed that the expression level of MYOZ2 protein in gastric cancer
      tissues was significantly increased compared with that in the corresponding
      adjacent healthy tissues (p<0.05). In-vitro growth, migration and invasion
      abilities of MYOZ2 positive gastric cancer cells were significantly higher than
      those of normal tissue cells. Univariate analysis showed that the high expression
      level of MYOZ2 in gastric cancer tissues was closely related to tumor size, lymph
      node metastasis, and pathological tumor-node-metastasis (pTNM) staging (p<0.05),
      but not associated with gender, age, differentiation degree, and tumor location
      (p>0.05). The 1-, 3- and 5-year survival rates of patients with low expression
      level of MYOZ2 (n=130) were higher than those of patients with high expression
      level of MYOZ2 (n=128). Multivariate analysis revealed that the expression level
      of MYOZ2 (p=0.000), lymph node metastasis (p=0.002), and pTNM staging (p=0.015)
      were independent risk factors influencing the prognosis of gastric cancer.
      CONCLUSIONS: Our results showed that the expression level of MYOZ2 may play an
      important role in the occurrence and development of gastric cancer, and can also
      provide references for the clinical diagnosis and treatment of gastric cancer.

PMID- 30280774
TI  - CD82/KAI1 inhibits invasion and metastasis of esophageal squamous cell carcinoma
      via TGF-beta1.
AB  - OBJECTIVE: Previous studies have found that CD82/KAI1 is a tumor suppressor gene.
      However, the role of CD82/KAI1 in esophageal squamous cell carcinoma (ESCC) has
      not been reported. This study aims to investigate the specific role of CD82/KAI1
      in ESCC, so as to further explore the relationship between CD82/KAI1 expression
      and clinical characteristics of ESCC. PATIENTS AND METHODS: The expression of
      CD82/KAI1 in 96 pairs of ESCC tissues and adjacent normal tissues was detected by
      Real-time quantitative polymerase chain reaction (qRT-PCR). The relationship
      between CD82/KAI1 expression and the pathological indicators of ESCC patients was
      analyzed by Kaplan-Meier method. QRT-PCR further validated the expression level
      of CD82/KAI1 in ESCC cells. In addition, the CD82/KAI1 knockdown expression model
      was constructed using small interfering RNA in ESCC cell lines TE-1 and EC-109
      cells. Cell counting kit-8 (CCK-8) and transwell assay were performed to detect
      cell viability, invasion and migration. Finally, the potential mechanism of
      CD82/KAI1 in regulating ESCC was explored using Western blot. RESULTS: QRT-PCR
      results showed that the expression level of CD82/KAI1 in ESCC was significantly
      lower than that of normal tissues, and the difference was statistically
      significant. Higher rates of lymph node metastasis and distant metastasis, as
      well as shorter overall survival were observed in ESCC patients with lower
      expression of CD82/KAI1 compared with those with higher expression. CD82/KAI1
      overexpression decreased cell proliferation, invasion and metastasis in ESCC
      cells. Western blot results showed that the expressions of TGF-beta1, Smad2/3,
      MMP-2 and MMP-9 were regulated by CD82/KAI1. In addition, rescue experiments
      demonstrated an interaction between CD82/KAI1 and TGF-beta1, indicating that
      CD82/KAI1 inhibits the malignant progression of ESCC via regulating TGF-beta1.
      CONCLUSIONS: Lowly expressed CD82/KAI1 in ESCC was significantly associated with
      the pathological stage, distant metastasis and poor prognosis of ESCC patients.
      CD82/KAI1 may inhibit the malignant progression of ESCC by interacting with TGF
      beta1.

PMID- 30280775
TI  - High expression of lncRNA MEG3 participates in non-small cell lung cancer by
      regulating microRNA-7-5p.
AB  - OBJECTIVE: This study was made to investigate whether long noncoding RNA (lncRNA)
      MEG3 could participate in the occurrence and development of non-small cell lung
      cancer (NSCLC) by regulating the expression of BRCA1 through competitive binding
      to microRNA-7-5p. PATIENTS AND METHODS: We used quantitative Real Time-Polymerase
      Chain Reaction (qRT-PCR) to explore the expression of lncRNA MEG3 and BRCA1 in
      NSCLC tissues and adjacent normal tissues, as well as NSCLC cell lines. The dual
      luciferase reporter gene assay was used to detect the binding of microRNA-7-5p to
      lncRNA MEG3 and BRCA1. Meanwhile, the expression of BRCA1, B-cell lymphoma-2 (Bcl
      2) and BCL2-associated X (Bax) was detected by Western blot after the cells were
      overexpressed or knocked down of lncRNA MEG3. All these experiments were designed
      to investigate whether lncRNA MEG3 participated in the pathogenesis of NSCLC
      through inhibiting the expression of BRCA1 and Bcl-2 and promoting Bax
      expression. RESULTS: The expressions of lncRNA MEG3 and BRCA1 in NSCLC tissues
      and A549 and HCC823 cell lines were significantly lower than those in the normal
      group. Overexpression of lncRNA MEG3 and BRCA1 in A549 and HCC823 cell lines
      resulted in increased apoptosis of lung cancer cells. Dual luciferase reporter
      assay demonstrated that lncRNA MEG3 can regulate the expression of BRCA1 through
      competitively binding to microRNA-7-5p to form the lncRNA MEG3/microRNA-7
      5p/BRCA1 regulatory network. Besides, lncRNA MEG3 could inhibit the apoptosis
      inhibitory protein Bcl-2 and promote the expression of apoptosis-promoting factor
      Bax. CONCLUSIONS: LncRNA MEG3 was significantly downregulated in NSCLC, and it
      could regulate the BRCA1 expression by competitive binding to microRNA-7-5p.

PMID- 30280776
TI  - LncRNA H19 serves as a ceRNA and participates in non-small cell lung cancer
      development by regulating microRNA-107.
AB  - OBJECTIVE: To investigate whether lncRNA H19 can regulate NF1 expression through
      competitive binding to microRNA-107, thereby participating in the occurrence and
      development of non-small cell lung cancer (NSCLC). PATIENTS AND METHODS:
      Expression levels of H19 and NF1 in NSCLC tissues, paracancerous tissues and
      NSCLC cell lines were detected by quantitative reverse transcriptase-polymerase
      chain reaction (qRT-PCR). The binding condition of microRNA-107, H19 and NF1 was
      detected by dual-luciferase reporter gene assay. Corresponding lentiviruses of
      H19 were constructed. The regulatory effects of H19 on proliferative and
      migratory abilities of A549 cells were detected by cell counting kit-8 (CCK-8)
      and transwell assay, respectively. Rescue experiments were conducted to explore
      the regulatory interaction between H19 and microRNA-107 in A549 cells. RESULTS:
      H19 and NF1 were highly expressed in NSCLC tissues and NSCLC cell lines (A549 and
      HCC823) than those of controls. Overexpressed H19 increased proliferative and
      migratory abilities of A549 cells. Dual-luciferase reporter gene assay
      demonstrated that H19 regulates NF1 expression through competitive binding to
      microRNA-107, thereafter participating in NSCLC development. CONCLUSIONS: H19 is
      highly expressed in NSCLC, which promotes NSCLC development by regulating NF1 via
      competitive binding to microRNA-107.

PMID- 30280777
TI  - MicroRNA-590-5p suppresses the proliferation and invasion of non-small cell lung
      cancer by regulating GAB1.
AB  - OBJECTIVE: Some specific microRNAs (miRNAs) have been identified to regulate the
      tumorigenesis of non-small cell lung cancer (NSCLC). MiR-590-5p was found to
      involve in the carcinogenesis of human cancers. This study aims at exploring the
      role of miR-590-5p in the pathogenesis of NSCLC. PATIENTS AND METHODS: The
      expressions of miR-590-5p and GAB1 were measured by quantitative Real-Time
      Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. The
      biological functions of miR-590-5p and GAB1 on cell viability and invasion were
      investigated through MTT and transwell assays. The binding site between miR-590
      5p and GAB1 was verified by dual-luciferase reporter gene assay (DLR). RESULTS:
      MiR-590-5p expression was downregulated in NSCLC. MiR-590-5p overexpression
      inhibited the proliferation and invasion of NSCLC cells. Furthermore, miR-590-5p
      was confirmed to directly target GAB1. GAB1 knockdown had the same effect as
      overexpression of miR-590-5p in NSCLC. Moreover, overexpression of GAB1 partially
      reversed the suppressive effect of miR-590-5p on NSCLC. CONCLUSIONS: MiR-590-5p
      suppressed cell proliferation and invasion of NSCLC by inhibiting GAB1
      expression, indicating that miR-590-5p was a suppressive miRNA in NSCLC.

PMID- 30280778
TI  - MiR-940 inhibits the progression of NSCLC by targeting FAM83F.
AB  - OBJECTIVE: We investigate whether miR-940 could target family sequence similarity
      83 member F (FAM83F) and further inhibit the progression of non-small cell lung
      cancer (NSCLC). PATIENTS AND METHODS: The expression levels of miR-940 and FAM83F
      in tumor tissues and paracancerous tissues of 72 NSCLC patients were detected
      through quantitative real time-polymerase chain reaction (qRT-PCR). The
      relationship between their expression levels, tumor size, and prognosis of NSCLC
      was analyzed. Transfection plasmids were constructed to knockdown or overexpress
      miR-940 in H1299 cells (inhibitor group) and SK-MES-1 cells (mimic group). The
      viability of H1299 cells and SK-MES-1 cells was evaluated using cell counting kit
      8 (CCK-8) assay after transfection. The combination of miR-940 and Ago2 was
      confirmed by RNA immunoprecipitation (RIP) experiment. The binding condition of
      miR-940 in FAM83F-WT and FAM83F-MUT groups was verified by luciferase reporter
      gene assay. RESULTS: MiR-940 expression was noticeably decreased, while FAM83F
      expression was distinctly upregulated in NSCLC tissues than that of paracancerous
      tissues. The overall survival rate of NSCLC patients with highly-expressed miR
      940 was significantly higher than those with lowly-expressed miR-940. Besides,
      miR-940 level was negatively correlated with tumor stage and size of NSCLC
      patients. Knockdown of miR-940 evidently enhanced the activity of H1299 cells,
      while overexpression of miR-940 decreased the viability of SK-MES-1 cells. In
      addition, miR-940 was confirmed to combine with FAM83F. Luciferase activity of
      cells co-transfected with FAM83F-WT and miR-940 mimic was significantly
      decreased. CONCLUSIONS: MiR-940 inhibited the proliferation of cancer cells by
      targeting FAM83F and further restrained the progression of NSCLC.

PMID- 30280779
TI  - MicroRNA-217 alleviates development of non-small cell lung cancer by inhibiting
      AKT3 via PI3K pathway.
AB  - OBJECTIVE: To explore the role of microRNA-217 in non-small cell lung cancer
      (NSCLC) and its underlying mechanism. PATIENTS AND METHODS: MicroRNA-217
      expression in 48 NSCLC tissues and paracancerous tissues were detected by qRT-PCR
      (quantitative Real-time polymerase chain reaction). The relationship between
      microRNA-217 expression and prognosis of NSCLC patients was analyzed. Target gene
      of microRNA-217 was predicted by bioinformatics method and further verified by
      luciferase reporter gene assay. Cell proliferation, cell cycle and apoptosis were
      detected after altering microRNA-217 expression in NSCLC cells. The effect of
      microRNA-217 on regulating PI3K pathway was detected by Western blot. RESULTS:
      MicroRNA-217 was downregulated in NSCLC tissues than that of paracancerous
      tissues. Shorter overall survival (OS) was observed in NSCLC patients with lower
      expression of microRNA-217 than those with higher expression. Overexpressed
      microRNA-217 remarkably inhibited proliferation and cell cycle, whereas induced
      apoptosis of NSCLC cells. AKT3 was screened out to be the target gene of microRNA
      217. Western blot results demonstrated that microRNA-217 upregulated AKT3 and
      PI3K pathway-related genes. CONCLUSIONS: Downregulated microRNA-217 promotes the
      occurrence and progression of NSCLC through upregulating AKT3 via PI3K pathway.

PMID- 30280780
TI  - HDAC1 is indirectly involved in the epigenetic regulation of p38 MAPK that drive
      the lung cancer progression.
AB  - OBJECTIVE: p38 MAPK are a class of protein kinase that may induce or prevent
      apoptosis in different circumstance. Emerging researches show that it plays a
      vital role in tumor progression and therefore understanding its dual role in
      different stages of lung cancer are important to investigate. Also in this study,
      we planned to understand its upstream target proteins like HDAC1 and uPAR which
      are responsible for p38 MAPK activation in the pathway. MATERIALS AND METHODS: We
      initially develop lung cancer mice model by exposing them to high nicotine
      content tobacco smoke. The pathological stages of initial and advanced lung
      cancer are observed and confirmed through histological sectioning. The expression
      of HDAC1, uPAR and p38 MAPK are observed and analyzed in different stages of lung
      cancer using immunohistochemistry and Western blotting. RESULTS: After 4 and 6
      months of regular exposure of high nicotine content smoke, the A/J strain mice
      develop initial and advanced stage of lung cancer. The initial stage cancer
      develops thick tissue layers with fibrosis whereas advanced stages of lung cancer
      show more proliferative cells. The expression of HDAC1 and uPAR shows the minimal
      expression pattern in control and initial stages of lung cancer, but its
      expression increased in advanced stage of cancer. In case of phospho-p38 MAPK,
      mild expression was observed almost in every individual cell in the initial
      stages of cancer, which implies its protective role in preventing advanced stage
      of cancer. But in advanced stage of lung cancer, we observed dysregulated
      overexpression of phospho-p38 MAPK. CONCLUSIONS: The epigenetic regulation of
      uPAR by HDAC1 confirms its indirect role in regulating p38 MAPK as tumor
      progress.

PMID- 30280781
TI  - MiR-410 affects the proliferation and apoptosis of lung cancer A549 cells through
      regulation of SOCS3/JAK-STAT signaling pathway.
AB  - OBJECTIVE: Janus kinase (JAK) - signal transducer and activator of transcription
      (STAT) signal pathway participates in regulating cell proliferation,
      differentiation, and apoptosis, and is correlated with non-small cell lung cancer
      (NSCLC) onset. Suppressors of cytokine signaling 3 (SOCS3) negatively regulates
      JAK-STAT pathway. SOCS3 is down-regulated in NSCLC tissues, with an elevation of
      miR-410 expression. This study thus intends to investigate if miR-410 plays a
      role in mediating NSCLC onset and underlying mechanism in this regulatory
      process. PATIENTS AND METHODS: NSCLC patients were collected for tumor and
      adjacent tissues, among which, miR-410 and SOCS3 expression were measured. Dual
      luciferase reporter gene assay was employed to confirm the targeting relationship
      between miR-410 and SOCS3. Their expression levels were compared between A549 and
      BEAS-2B cells. Cultured A549 cells were treated with anti-miR-410 and/or SOCS3.
      Expression levels of SOCS3, p-JAK1/2, p-STAT3, and Bcl-2 were compared along with
      the apoptotic rate of cells. RESULTS: Bioinformatics analysis revealed targeted
      binding site between miR-410 and 3'-UTR of SOCS3 mRNA. Compared to those in tumor
      tissues, a significant increase of miR-410 and reduction of SOCS3 were found in
      NSCLC tissue (p < 0.05). Dual luciferase reporter gene assay indicated that SOCS3
      was targeted regulated by miR-410. Significantly higher miR-410 and lower SOCS3
      levels were shown in A549 cells, compared to those in BEAS-2B cells. Transfection
      of anti-miR-410 and/or SOCS3 in A549 cells, SOCS3 expression and apoptosis were
      significantly induced, while JAK1, JAK2, and STAT3 phosphorylation were
      statistically decreased with the reduction of the Bcl-2 level (p < 0.05).
      CONCLUSIONS: miR-410 level was increased while SOCS3 expression was declined in
      NSCLS tissues. MiR-410 induces the apoptosis of A549 cells through downregulating
      JAK/STAT3/SOCS3 signaling pathway, which provides new insights for the therapy of
      pulmonary carcinoma in clinic.

PMID- 30280782
TI  - MiR-410 affects the proliferation and apoptosis of lung cancer A549 cells through
      regulation of SOCS3/JAK-STAT signaling pathway.
AB  - OBJECTIVE: Larynx carcinoma is a common head-neck malignant tumor. Recent
      investigations showed the involvement of microRNA (miR) in regulation of multiple
      tumors. miR-140-5p showed decreased expression in various cancers, but without
      knowledge regarding its expression in larynx carcinoma and effects on cell
      invasion and angiogenesis. MATERIALS AND METHODS: Real-time quantitative PCR was
      firstly employed to measure miR-140-5p expression in larynx carcinoma and
      controlled tumor adjacent tissues. In larynx cancer cell line, agomir or
      antagomir of miR-140-5p was applied to up-regulate or down-regulate miR-140-5p,
      respectively. Western blot was used to evaluate vascular endothelial growth
      factor A (VEGF-A) expression, and cell proliferation was modified by 3-(4,5
      dimethyl-2-thiazolyl)-2,5-diphenyl-2-H- tetrazolium bromide (MTT) approach.
      Transwell approach was used to measure cell invasion, and angiogenesis assay was
      used to detect the effect on angiogenesis. Luciferase report assay (LRA) measured
      targeting binding between miR-140-5p and VEGF-A. RESULTS: Comparing to tumor
      adjacent tissues, larynx carcinoma cells showed significantly decreased miR-140
      5p expression. Agomir up-regulated miR-140-5p expression and weakened
      proliferation and invasion potency, and inhibited angiogenesis. Antagomir down
      regulated miR-140-5p and presented the opposite results. Finally, LRA confirmed
      direct binding between miR-140-5p and VEGF-A. CONCLUSIONS: MiR-140-5p can target
      VEGF-A in larynx carcinoma cell line to inhibit cell invasion and angiogenesis.
      MiR-140-5p thus may work as the direct molecular target of larynx carcinoma.

PMID- 30280783
TI  - LncRNA LET function as a tumor suppressor in breast cancer development.
AB  - OBJECTIVE: To evaluate the effect of long-chain non-coding RNA LET (lncRNA LET)
      on the regulatory of human breast cancer and its underlying mechanism. PATIENTS
      AND METHODS: The expression levels of lncRNA LET in breast cancer tissues, MDA-MB
      231 cells and MCF-10A breast epithelial cells were detected by quantitative Real
      Time Polymerase Chain Reaction (qRT-PCR). The proliferation of lncRNA LET was
      detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide).
      Cell apoptosis was examined via flow cytometry. The invasion and migration of
      cells were detected by transwell and scratch assay. RESULTS: The expression of
      lncRNA LET was reduced in breast cancer tissues and MDA-MB-231 cells.
      Overexpression of lncRNA LET resulted in the inhibition of cell proliferation,
      invasion and migration ability, and promotion of cell apoptosis (p<0.05). Up
      regulation of lncRNA LET repressed epithelial mesenchymal transition (EMT)
      process. CONCLUSIONS: LncRNA LET is a new type of molecule involved in the
      development of breast cancer, which may become a potential target for the
      treatment of breast cancer.

PMID- 30280784
TI  - Jagged2 promotes cancer stem cell properties of triple negative breast cancer
      cells and paclitaxel resistance via regulating microRNA-200.
AB  - OBJECTIVE: To investigate the role of Jagged2 in triple negative breast cancer
      (TNBC) and its underlying mechanism. PATIENTS AND METHODS: Breast cancer tissues
      of patients diagnosed with TNBC in Fujian Medical University Affiliated MinDong
      Hospital from January 2015 to September 2017 were selected. TNBC patients were
      divided into the paclitaxel-resistant group (n=34) and non-resistance group
      (n=11). Jagged2 expression in paclitaxel-resistant group and non-resistance group
      before and after treatment was detected by quantitative Real-time-polymerase
      chain reaction (qRT-PCR), respectively. After Jagged2 knockdown in paclitaxel
      resistant MDA-MB-231 cells (MDA-MB-231/TXR), expression of CD44+CD24-ESA+ subset
      was detected by flow cytometry. MicroRNA-200 expression was detected after
      Jagged2 knockdown in MDA-MB-231/TXR cells. RESULTS: Jagged2 was highly expressed
      in paclitaxel-resistant TNBC tissues and cells. Jagged2 expression was found to
      be associated with cancer stem cell (CSC) properties of TNBC cells. Knockdown of
      Jagged2 inhibited CSC properties and paclitaxel resistance, whereas upregulated
      microRNA-200 expression. The inhibited CSC properties and paclitaxel resistance
      induced by Jagged2 knockdown were reversed by microRNA-200 knockdown.
      CONCLUSIONS: Jagged2 maintains CSC properties of TNBC cells and paclitaxel
      resistance via regulating microRNA-200.

PMID- 30280785
TI  - Central nervous disease in pediatric patients during acute lymphoblastic leukemia
      (ALL): a review.
AB  - Acute lymphoblastic leukemia (ALL) is one of the frequently reported malignancies
      of childhood age. Earlier it was thought to be a fatal pathological state with no
      cure, but with advancements in medicine and science, new therapeutic approaches
      have resulted in better management and cure. However, one of the major hurdles in
      achieving a complete cure is the relapse of ALL at extra-medullary sites like the
      central nervous system (CNS). The present review article is focused on recent
      diagnostic avenues available for the detection of CNS disease during acute
      lymphoblastic leukemia (ALL) in young patients.

PMID- 30280786
TI  - The therapeutic efficacy of pediatric ALL patients with MLL gene rearrangement
      treated with CCLG-ALL2008 protocol.
AB  - OBJECTIVE: In this study, we retrospectively evaluated the therapeutic efficacy
      of China Children Leukemia Group-ALL2008 (CCLG-ALL 2008) protocol in pediatric
      patients with mixed-lineage leukaemia (MLL) gene rearrangement of acute
      lymphoblastic leukemia (ALL) to identify the prognostic factors. PATIENTS AND
      METHODS: Six hundred and thirty-four patients with ALL were enrolled in this
      study between June 2008 and Dec 2014. High-risk group (HR) consisted of 217
      cases, of which 28 cases were MLL related positive (first group), 22 cases were
      BCR/ABL positive (second group), and 167 cases were negative with MLL related or
      BCR/ABL (third group). The therapeutic efficacy was evaluated at the time points
      of day 8 (TP1), day 15 (TP2), day 33 (TP3) and 12th week (TP4) with the protocol,
      respectively. Overall-survival (OS) and relapse-free-survival (RFS) and treatment
      related mortality (TRD) were analyzed as well. RESULTS: The first group accounted
      for 4.4% of all patients. Compared with the second and third group, the first
      group had more cases younger than 2 years, with initial leukocytes >=50*109/L,
      and poor response on TP2. Moreover, patients older than 2 years old had a good 5
      years OS (84% +/- 9% vs. 37% +/- 20%, p<0.05) and RFS (84% +/- 9% vs. 29% +/-
      17%, p<0.05). There were no significant differences in the recurrence rate, TRD,
      5 years OS and RFS among three groups. For the first group, compared with good
      response to prednisone, patients with poor response to prednisone had a poor 5
      years RFS (41% +/- 17% vs. 81% +/- 10%, p<0.05). Multivariate Cox regression
      analysis identified that RFS and OS were influenced by such factors as age, MLL
      fusion partners, and prednisone response (p<0.05). CONCLUSIONS: Such factors as
      younger age than 2 years old, MLL/AF4 fusion gene, poor response to prednisone,
      or no complete remission (CR) on TP3 were poor prognostic parameters in
      predicting the outcome in childhood ALL with MLL gene rearrangement treated with
      CCLG-ALL 2008 protocol.

PMID- 30280787
TI  - DUSP facilitates RPMI8226 myeloma cell aging and inhibited TLR4 expression.
AB  - OBJECTIVE: Myeloma severely threatens public health, and molecular targeting
      treatment becomes the future perspective. Dual specificity phosphatases (DSUP)
      protein has multiple functions including modulating cell proliferation,
      differentiation, aging, and apoptosis. Whether DUSP can regulate myeloma cell is
      unclear. This study thus aimed to investigate the effect of DUSP on myeloma cell
      line RPMI8226 cell aging and provide evidence for the clinical treatment of
      myeloma. MATERIALS AND METHODS: H2O2-induced aging model of myeloma cell line
      RPMI8226 was generated. DUSP over-expression plasmid or specific siRNA was
      transfected by liposome. Western blot was used to detect the expression of DUSP
      in RPMI8226 cells. Cell aging condition was evaluated by beta-galactosidase
      assay. Aging proteins P53 and P16 expression levels, the activation of TLR4
      signal pathway were tested by immunoblotting. TLR4 signal pathway was then
      suppressed by Verteporfin for testing RPMI8226 cell aging. RESULTS: Growing
      levels of DUSP, aging proteins P53 and P16, with inhibition of TLR4 signal
      pathway were found in the H2O2-induced aging model of myeloma cell line RPMI8226.
      Transfection of DUSP over-expression plasmid or siRNA potentiated or inhibited
      the aging of RPMI8226 cells induced by H2O2 and suppressed or enhanced TLR4
      signal pathway, respectively. Verteporfin, an inhibitor of TLR4, increased the
      level of P53 and aging of RPMI8226 cells. CONCLUSIONS: DUSP facilitates H2O2
      induced aging of myeloma cell line RPMI8226 and suppresses TLR4 expression, which
      provides academic basis for clinical intervention.

PMID- 30280788
TI  - SETD5-AS1 stimulates neuron death in stroke via promoting PTEN expression.
AB  - OBJECTIVE: To investigate the specific role of long non-coding RNA (lncRNA) SETD5
      AS1 in regulating stroke development, and its underlying mechanism. MATERIALS AND
      METHODS: Middle cerebral artery occlusion (MCAO) model and OGD/R (oxygen-glucose
      deprivation/reoxygenation) model were constructed for exploring the mechanism of
      ischemia-reperfusion injury induced by ischemic stroke. SETD5-AS1 expression in
      brain tissues of ischemic stroke mice and control mice was detected by
      quantitative Real-time-polymerase chain reaction (qRT-PCR). Proliferation and
      apoptosis of N2a cells were detected after transfection of overexpression plasmid
      or siRNA SETD5-AS1. The downstream gene of SETP5-AS1 was predicted by Starbase
      and PTEN was screened out. Both mRNA and protein expressions of PTEN in MCAO
      model and OGD/R model were detected. Furthermore, the binding condition of SETD5
      AS1 and PTEN was verified by dual-luciferase reporter gene assay, RNA pull-down
      assay and RNA binding protein immunoprecipitation (RIP). The regulatory effect of
      SETD5-AS1 on PI3K/AKT pathway was detected by Western blot. RESULTS: SETD5-AS1
      was highly expressed in the ischemia-reperfusion injury model. Overexpression of
      SETD5-AS1 in N2a cells resulted in increased apoptosis and decreased
      proliferation. PTEN expression was upregulated in MCAO model and OGD/R model.
      Dual-luciferase reporter gene assay indicated that SETD5-AS1 can promote PTEN
      transcription. The binding condition of SETD5-AS1 and PTEN was further verified
      by RNA pull-down assay and RIP. Overexpression of SETD5-AS1 in N2a cells
      inhibited PI3K/AKT pathway. CONCLUSIONS: SETD5-AS1 is highly expressed in the
      ischemia-reperfusion injury model. SETD5-AS1 participates in the development of
      ischemic stroke by activating PTEN and inhibiting PI3K/AKT pathway.

PMID- 30280789
TI  - Effects of IL-1beta on hippocampus cell apoptosis and learning ability of
      vascular dementia rats.
AB  - OBJECTIVE: Vascular dementia (VD) is a type of memory, cognition, and behavior
      disorder caused by ischemic stroke or hemorrhagic stroke. It is a common
      pathogenesis of dementia that is only second to Alzheimer's disease. Inflammation
      plays a key role in VD. Interleukin-1beta (IL-1beta) is a kind of pro
      inflammatory cytokine, while its mechanism in VD occurrence and development is
      still unclear. MATERIALS AND METHODS: The healthy male rats were randomly divided
      into three groups, including sham group, VD model group (established by bilateral
      common carotid artery ligation), and IL-1beta group (treated by IL-1beta
      monoclonal antibody intracerebroventricular injection on based on model group).
      Rat learning ability was evaluated by Morris water maze assay. IL-1beta
      expression in brain tissue and peripheral blood was examined by using Real Time
      PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Hippocampus
      apoptosis was detected by caspase 3 activity detection kit. B-cell lymphoma-2
      (Bcl-2) and p38 mitogen-activated protein kinase (MAPK) protein levels were
      assessed by Western blot assay. RESULTS: IL-1beta expression was increased,
      caspase 3 activity was enhanced, Bcl-2 level was declined, and p-P38
      phosphorylation was elevated in brain tissue and peripheral blood from VD model
      group compared to sham group (p<0.05). IL-1beta monoclonal antibody significantly
      reduced IL-1beta expression, improved learning ability, attenuated caspase 3
      activity, increased Bcl-2 level, and declined p-P38 expression in VD rats
      compared to model group (p<0.05). CONCLUSIONS: IL-1beta can delay VD occurrence
      and development through the P38-MAPK signaling pathway to regulate cell apoptosis
      and improve learning ability.

PMID- 30280790
TI  - Inhibition of PARP overactivation protects acute kidney injury of septic shock.
AB  - OBJECTIVE: To evaluate pathological lesions in New Zealand white rabbits with
      acute kidney injury (AKI) of septic shock and to explore the potential role of
      poly (ADP-ribose) polymerase (PARP) in regulating AKI development. MATERIALS AND
      METHODS: Endotoxic shock model in New Zealand white rabbits was first
      constructed. CVP (central venous pressure) was maintained at the baseline level
      by the saline administration. Rabbits were randomly assigned into sham group, LPS
      group, and LPS+3-AB group, respectively. Blood samples and kidney samples of
      rabbits were collected 4 h after LPS administration. Pathological kidney lesions
      were observed by HE (hematoxylin-eosin) staining and immunohistochemistry. Serum
      levels of renal damage markers (Scr, Cys-C, KIM-1, and NGAL) were detected by an
      automatic biochemical analyzer, immunoturbidimetry, and ELISA (enzyme-linked
      immunosorbent assay), respectively. Kidney energy metabolism changes (ATP, ADP,
      PCr, and NAD) were detected by HPLC (high performance liquid chromatography
      analysis). Western blot was conducted to detect protein expressions of NF-kappaB
      (nuclear factor-kappa B), TNF-alpha (tumor necrosis factor-alpha), ICAM-1
      (intercellular cell adhesion molecule-1) and P-selectin in kidney tissues.
      RESULTS: Significant pathological lesions in kidney tissues and higher
      pathological grade were seen in the LPS group. Multiple PARP-positive nuclei were
      found in renal tubular cells at the junction of renal cortex and renal cortex in
      the LPS group. Serum levels of Scr, KIM-1, NGAL, and Cys-C were remarkably higher
      in the LPS group than those of sham group. HPLC results showed decreased levels
      of ATP, ADP, PCr, and NAD in kidney cortex of LPS group compared with those of
      sham group. Western blot results suggested that protein expressions of NF-kappaB,
      TNF-alpha, ICAM-1, and P-selectin were remarkably upregulated in kidney tissues
      of LPS group. 3-AB pretreatment, the PARP inhibitor, remarkably alleviated
      pathological lesions and inflammation induced by AKI. CONCLUSIONS: Inhibition of
      PARP overactivation alleviated pathological kidney lesions, improved kidney
      energy metabolism and inhibited inflammatory response resulted from AKI.

PMID- 30280791
TI  - IgG cryoglobulinemia.
AB  - OBJECTIVE: Mixed Cryoglobulinemia is the most well-known Hepatitis C Virus (HCV)
      associated extrahepatic manifestation. MC is both an autoimmune and B
      lymphoproliferative disorder. Cryoglobulins (CGs) are classified into three
      groups according to immunoglobulin (Ig) composition: type I is composed of one
      isotype or Ig class. Type II and type III mixed CGs are immune complexes composed
      of polyclonal IgGs acting as autoantigens and mono, polyclonal or oligoclonal IgM
      with rheumatoid factor activity. IgG1 and IgG3 are the predominant subclasses
      involved. This study shows the simultaneous presence of IgG-RF and IgG3,
      supporting the hypothesis of an involvement of this subclass in the initiation of
      early stages of CGs. PATIENTS AND METHODS: We describe a case series of six HCV
      positive patients, all of whom had peripheral neuropathy and transient ischemic
      attacks, presenting cryoprecipitates formed by IgG3 and IgG1. Cryoprecipitate IgG
      subclass research was carried out by immunofixation electrophoresis by using
      antisera against IgG1, IgG2, IgG3, and IgG4. RESULTS: Our six patients presented
      with an immunochemical pattern characterized by the mere presence of IgG1 and
      IgG3 subclasses with probable RF activity and one of these six patients exhibited
      monoclonal IgG3 in his cerebrospinal fluid. CONCLUSIONS: We can hypothesize that
      the IgG passage through the blood-brain barrier could have contributed to the
      cause of TIAs, through a mechanism involving the precipitation of circulating
      immune complexes formed by the two subclasses in the intrathecal vessels.

PMID- 30280792
TI  - Multilocus sequence typing for Candida albicans strains from the intestinal tract
      of patients with cirrhosis.
AB  - OBJECTIVE: Multilocus sequence typing (MLST) was applied to investigate the
      genetic diversity of Candida albicans in the intestinal tract of cirrhosis
      patients. PATIENTS AND METHODS: We used CHROM agar Candida medium to obtain 105
      Candida sp. isolates from fecal samples (276 subjects), including 63 isolates
      from the cirrhosis group (141 subjects) and 42 isolates from the healthy control
      group (135 subjects). RESULTS: Among the 105 Candida strains isolated, 60 strains
      were identified as Candida albicans. Patients with cirrhosis had significantly
      higher rates of colonization by Candida sp. (44.68% vs. 31.11%, p < 0.05) and C.
      albicans (27.66% vs. 15.56%, p < 0.05) relative to healthy controls. In the
      cirrhosis group, the rate of colonization further increased with disease
      progression and antibiotic treatment (p < 0.01). Sixty C. albicans isolates were
      analyzed by MLST. Fifty diploid sequence types (DST) were observed, and 26 new
      DSTs and 3 novel alleles were found. The majority of isolates were distributed
      among three clades, clade 8 (31.67%), clade 14 (15.00%) and clade 18 (21.67%).
      Among 39 strains from the cirrhosis group, 16 strains (41.02%) belonged to clade
      8, while only 3 strains (14.29%) from healthy group belonged to clade 8 (p <
      0.05). In addition, concatenated sequences of the 7 housekeeping gene fragments
      were analyzed for all the different DSTs in clade 8 to evaluate the loss of
      heterozygosity (LOH), which indicates C. albicans microvariation in the gut of
      cirrhosis patients. CONCLUSIONS: This study suggests that cirrhosis disease
      progression and antibiotic treatment is associated with increased colonization by
      Candida sp. and C. albicans. We are the first to provide MLST-based genotype
      profiles for C. albicans Guizhou China, and to identify clade 8 as the potential
      main clade of C. albicans colonization in the gut of cirrhosis patients.

PMID- 30280793
TI  - An analysis of the iatrogenic biliary injury after robotic cholecystectomy.
      Current data and future considerations.
AB  - OBJECTIVE: Minimally invasive techniques are the gold standard in surgery. Since
      conventional laparoscopic approach has been widely adopted, surgeons in their
      effort to further improve their skills passed to the era of the robotic
      assistance. The widespread adoption of robotics has led to the inevitable usage
      of robotic technology both in simple, as well as in more complicated procedures.
      Cholecystectomy is the "simple" surgical procedure to which every surgeon from
      the beginning of his career and besides specialization or subspecialization is
      exposed to, but the ran complications have a dramatic impact both for patient and
      doctor. The elimination of bile duct injury is crucial and robotics in the new
      era of surgery has to be the gold standard to a safe cholecystectomy. MATERIALS
      AND METHODS: A comprehensive search of PubMed Database was conducted for English
      language studies using the MeSH terms [Robotic cholecystectomy, bile duct
      injury]. We reviewed references of all reports for additional cases from 2000 to
      nowadays. We used the related articles link and searched the citations of reports
      in the ISI Science Citation Index to identify additional reports. RESULTS: A
      total of 16 studies, including 2.264 patients that underwent robotic
      cholecystectomy were analyzed. Postoperative data and complications were
      collected from these studies. Bile duct injuries were more likely to be
      discovered during the first postoperative days as a bile leakage (8/2.264). One
      major bile duct injury was noticed, and most injuries were definitively treated
      at the hospital where the injury occurred with postoperative endoscopic
      retrograde cholangiopancreatography (ERCP) and stenting. CONCLUSIONS: Robotic
      cholecystectomy is a safe and adequate alternative to conventional laparoscopic
      or open approach in term of safety. Furthermore, surgeons must be already
      experienced and familiar with robotic techniques, so as to overcome the problem
      of the bile duct injury.

PMID- 30280794
TI  - HIF-1alpha promotes inflammatory response of chronic obstructive pulmonary
      disease by activating EGFR/PI3K/AKT pathway.
AB  - OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is an incomplete,
      reversible disease with progressive inflammation obstruction in airways. This
      study aims to explore the regulatory mechanism of hypoxia-inducible factor-1alpha
      (HIF-1alpha) in inflammatory response and progression of COPD. PATIENTS AND
      METHODS: 71 bronchoalveolar lavage fluid (BALF) samples were collected, including
      59 samples from COPD patients (COPD group) and 12 from patients with normal
      pulmonary function (control group). The mRNA and protein levels of HIF-1alpha and
      epidermal growth factor receptor (EGFR) in BALF were detected by quantitative
      Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively.
      Serum levels of interleukin-13 (IL-13), IL-9, IL-1, and tumor necrosis factor
      alpha (TNF-alpha) were detected by enzyme-linked immunosorbent assay (ELISA).
      Hypoxia cell model was constructed by COCl2 induction in human embryonic lung
      cells. Expression levels of HIF-1alpha, EGFR and p-AKT in NCI-H1563 cells treated
      with 740Y-P, the phosphoinositide 3-kinase (PI3K) agonist were detected. Finally,
      we detected proliferation and apoptosis in NCI-H1563 cells with HIF-1alpha
      overexpression by cell counting kit-8 (CCK-8) assay and flow cytometry,
      respectively. RESULTS: The mRNA and protein levels of HIF-1alpha and EGFR were
      higher in COPD groups compared with those of control group. Serum levels of IL
      13, IL-9, IL-1, and TNF-alpha in COPD patients were elevated. CoCl2 induction in
      NCI-H1563 cells led to upregulated levels of IL-13, IL-9, IL-1, and TNF-alpha.
      740Y-P treatment remarkably activated EGFR/PI3K/AKT pathway. Overexpressed HIF
      1alpha inhibited proliferation but induced apoptosis of NCI-H1563 cells.
      CONCLUSIONS: HIF-1alpha was overexpressed in COPD, which upregulated expressions
      of inflammatory factors via activating the EGFR/PI3K/AKT pathway. The activated
      EGFR/PI3K/AKT pathway induced by pulmonary inflammation further upregulated HIF
      1alpha expression in a feedback loop, thus aggravating COPD pathological changes.

PMID- 30280796
TI  - The mechanisms of Ang II-induced hypertensive vascular remodeling under
      suppression of CD68 in macrophages.
AB  - OBJECTIVE: High blood pressure (hypertension) is one of the most common
      cardiovascular diseases. In recent years, there were more and more studies on the
      function of inflammation in hypertension. CD68 mainly mediates the activation of
      cytokine interleukin-17 (IL-17) signaling pathway and participates in
      inflammatory responses. It has been studied the function of CD68 and IL-17 in
      hypertension, but it has not been reported whether it affected hypertension and
      vascular remodeling when macrophage CD68 expression inhibited. In this study,
      antisense-CD68 mice were used to study the effect and mechanism of angiotensin II
      induced hypertensive vascular remodeling under specific suppression of macrophage
      CD68. MATERIALS AND METHODS: Fifty 8-week-old male antisense-CD681 and C57 mice
      were divided into control and experimental group (angiotensin II group, 1000
      ng*kg-1*min-1). After infusion of angiotensin II for 28 days, hematoxylin-eosin
      (HE) staining and immunohistochemical staining were used to observe the remodel
      of vascular. The changes of aortic inflammatory factors were detected by Real
      time PCR (RT-PCR) and Western blotting. RESULTS: By specifically inhibiting the
      expression of macrophage CD68, macrophage infiltration was mitigated in Ang II
      induced hypertensive vascular remodeling model mouse, which also down-regulated
      the expression of vascular tissue inflammatory factor and activation of vascular
      smooth muscle cell p65. CONCLUSIONS: CD68 regulates the Ang II-induced
      hypertensive vascular remodeling through mediating macrophage inflammatory factor
      release.

PMID- 30280795
TI  - IL-10 promotes development of acute respiratory distress syndrome via inhibiting
      differentiation of bone marrow stem cells to alveolar type 2 epithelial cells.
AB  - OBJECTIVE: To explore whether interleukin-10 (IL-10) could promote the
      development of acute respiratory distress syndrome (ARDS) via inhibiting
      differentiation of bone marrow stem cells (BMSCs) to alveolar type 2 (AT II)
      epithelial cells. PATIENTS AND METHODS: 25 ARDS (acute respiratory distress
      syndrome) patients admitted in our hospital from December 2015 to February 2018
      were enrolled. Meanwhile, 25 healthy controls in the same period were selected as
      control group. Serum level of IL-10 in each subject was detected via ELISA
      (enzyme-linked immunosorbent assay). BMSCs were isolated and cultured, followed
      by identification of surface antigens and morphology observation using flow
      cytometry. For in vitro experiments, expression levels of AT II-related genes
      induced with or without IL-10 were detected by qRT-PCR (quantitative Real-time
      polymerase chain reaction) and Western blot, respectively. The culture medium of
      BMSCs induced with or without IL-10 was collected for detecting expression levels
      of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha
      (TNF-alpha) by ELISA. RESULTS: IL-10 was overexpressed in ARDS patients than that
      of healthy controls. Primary BMSCs were elongated after culturing for 1-3 days.
      Negative-antigen CD34 (4.32%) and positive-antigen (99.87%) on the surface of
      BMSCs were identified by flow cytometry. Both mRNA and protein expressions of AT
      II-related genes increased in a time-dependent manner. ELISA results showed that
      IL-10 level in cell supernatant decreased with the prolongation of induction
      days. Moreover, IL-10 intervention downregulated the expressions of AT II-related
      genes. CONCLUSIONS: IL-10 promotes ARDS development via inhibiting cell
      differentiation of BMSCs to AT II.

PMID- 30280797
TI  - Correlation between adiponectin polymorphism and atherosclerotic plaque
      compositions under intravascular ultrasound (IVUS).
AB  - OBJECTIVE: To discuss the correlation between polymorphism of rs266729 (
      11377C/G, Cytosine/Guanine) (adiponectin promoter) site and atherosclerotic
      plaque compositions as well as related indicators under intravascular ultrasound
      (IVUS). PATIENTS AND METHODS: 76 patients with coronary heart disease from
      December 2014 to December 2016 were enrolled. The PCR-RFLP method was used to
      analyze the adiponectin gene polymorphism in rs266729 site. All the objects were
      divided into CC type group (n=26), CG type group (n=23), and GG type group (n=27)
      according to the results of polymorphism. The amount of lesions and length of
      lesion in the vessel were determined according to the images of coronary
      angiography. The indicators from each group, including minimum external elastic
      membrane area, the smallest lumen area, the patch area, the patch load, the lipid
      pool area, the lipid pool/plaque area, the fiber cap thickness, the
      reconstruction index, the positive reconstruction, the negative reconstruction
      and the patch character were measured according to the IVUS results. RESULTS: The
      baseline data from distinct the gene types showed no significant difference. The
      results of quantitative IVUS plaque analysis indicated a statistical difference
      of factors such as plaque area, plaque burden, lipid pool area, lipid pool/plaque
      area, and remodeling index between the CC and GG types (p<0.05). The levels of
      aminopeptidase N (APN), tumor necrosis factor alpha (TNF-alpha), interleukin 1
      beta (IL-1beta), fasting serum insulin (FIN), triglyceride (TG), and low-density
      lipoprotein cholesterol (LDL-C) among diverse groups presented statistical
      difference (p<0.05). Of note, the analysis results of IVUS qualitative components
      of plaque showed that soft plaque in CC group was 42.3% (11/26), which was
      significantly lower than GG group 11.1% (3/27) (p<0.05). The vascular remodeling
      ratio in CC group 26.9% (7/26) was also significantly decreased compared to that
      in GG group 66.7% (18/27) (p<0.05). The tubular and diffuse ratio in CC groups
      according to the comparison of diseased vessel, count, length of the lesion were
      34.6% (9/26) and 42.3% (11/26), respectively. CONCLUSIONS: Our data on
      biochemical indicators demonstrates CC type gives rise to poor prognosis compared
      to GG type does, which suggests that close attention should be paid in the impact
      of adiponectin polymorphism on atherosclerotic plaque compositions.

PMID- 30280798
TI  - Down-regulation of miR-192 protects against rat ischemia-reperfusion injury after
      myocardial infarction.
AB  - OBJECTIVE: DJ-1-phosphate and tension homology deleted on chromosome
      ten/phosphatidylinositol-3-kinase/protein kinase B (PTEN/PI3K/AKT) signaling
      pathway plays a role in the regulation of ischemic reperfusion (I-R) injury.
      Bioinformatics analysis demonstrated that there is a complementary binding site
      between microRNA-192 (miR-192) and the 3'-UTR of DJ-1 mRNA. This study
      investigated the role of miR-192 in regulating DJ-1-PTEN/PI3K/AKT signaling
      pathway and myocardial I-R injury. MATERIALS AND METHODS: miR-122 and DJ-1 mRNA
      expressions in myocardial tissue were detected by Real-time PCR (RT-PCR). DJ-1,
      PTEN, and phosphorylated AKT (p-AKT) protein expressions were tested by Western
      blot. Reactive oxygen species (ROS) content was measured by flow cytometry.
      Malondialdehyde (MDA) content and superoxide dismutase (SOD) enzyme activity were
      detected by the kits. I-R treatment was performed at 72 h after transfection.
      Cell apoptosis was evaluated with flow cytometry. RESULTS: Compared with sham
      group, miR-192, PTEN expressions and MDA content were significantly increased
      (p<0.05), while DJ-1, p-AKT levels and SOD activities were significantly reduced
      (p<0.05) in myocardial tissue of I-R group. Compared with control, I-R treatment
      significantly up-regulated miR-192 level, significantly decreased DJ-1 and p-AKT
      proteins, significantly elevated PTEN expression, and significantly induced
      apoptosis and ROS production in H9C2 cells (p<0.05). Transfection of miR-192
      inhibitor significantly enhanced DJ-1 level, declined PTEN expression, elevated p
      AKT level, and restrained apoptosis, ROS production and MDA content, and promoted
      SOD activity in H9C2 cells under I-R condition. CONCLUSIONS: The expression of
      miR-192 increased significantly, while the expression of DJ-1 reduced obviously
      during I-R injury after myocardial infarction. Down-regulation of miR-192
      markedly enhanced DJ-1 expression and PTEN/PI3K/AKT pathway activity, inhibited
      cell apoptosis and ROS generation, and reduced I-R injury in cardiomyocytes.

PMID- 30280799
TI  - MiR-223 promotes cardiomyocyte apoptosis by inhibiting Foxo3a expression.
AB  - OBJECTIVE: MicroRNAs (miRs) are proven to possess diversified functions in the
      pathogenesis of cardiac diseases. The current study is designed aiming at
      determining the effect of miR-223 on oxidative stress induced apoptosis in
      cardiomyocytes. MATERIALS AND METHODS: Mouse model of myocardial infarction (MI)
      was constructed, and endogenous level of miR-223 in the border zone of infarcted
      heart tissues was determined. Primarily cultured cardiomyocytes were exposed to
      H2O2 treatment to mimic the oxidative stress stimulation. Multiple approaches
      including quantitative reverse transcription polymerase chain reaction (qRT-PCR),
      cell viability assay, luciferase assay, Western blot assay and flow cytometry
      assay were employed to determine its expression, function and mechanism in
      apoptosis. RESULTS: MiR-223 expression was significantly upregulated in the
      border zone of infarcted heart ventricular tissues and in cardiomyocytes treated
      with H2O2. Overexpression of miR-223 in cardiomyocytes promoted apoptosis,
      whereas inhibition of endogenous miR-223 protected cardiomyocytes from oxidative
      stress induced apoptosis. MiR-223 directly targets the 3'untranslated region
      (UTR) of Foxo3a mRNA. Overexpression of miR-223 inhibited Foxo3a protein
      expression, however, inhibition of miR-223 suppressed its expression. Silencing
      Foxo3a using small interfering RNA (siRNA) mimicked the effect of miR-223,
      indicating its functional significance. CONCLUSIONS: MiR-223 is an important
      regulator of cardiomyocyte apoptosis under oxidative stress. Inhibition of the
      miR-223/Foxo3a signaling axis may be a potential therapeutic strategy for cardiac
      injuries.

PMID- 30280800
TI  - Using intra-articular tranexamic acid in total knee replacement surgery with and
      without bleeding control: a prospective randomized double blind study.
AB  - OBJECTIVE: To investigate the effectiveness of tranexamic acid (TA) application
      in two techniques: in the first one wound closure is performed before the
      tourniquet is released; in the second one, wound closure is performed after the
      tourniquet is released. PATIENTS AND METHODS: The study is conducted on four
      groups of patients: (1) TA + TNR (tourniquet not released) where there is no
      bleeding control and TA is applied after wound closure without tourniquet
      release; (2) TA - TNR where placebo is applied after wound closure without
      tourniquet release; (3) TA + TR (tourniquet released) where tourniquet is
      released first and TA is applied after bleeding control and wound closure; and
      (4) TA - TR where tourniquet release is followed by bleeding control and placebo
      application. RESULTS: The amount of hemorrhage in hemovac drains in each group
      was as follows: 217.4 +/- 99.6 (100-590) ml in the TA + TNR group; 411.6 +/-
      133.7 (175-850) ml in the TA - TNR group; 291.2 +/- 89.5 (160-650) ml in the TA +
      TR group; and 458.2 +/- 138.6 (200-920) ml in the TA - TR group (p<0.0001). The
      TA + TNR group differed significantly from other groups in terms of the
      hemorrhage in drains.  Similarly, the TA + TNR group was notably different from
      the TA - TNR and TA - TR groups with regard to the hemoglobin and hematocrit
      values. CONCLUSIONS: The study reveals that the amount of blood in hemovac drains
      is reduced significantly after the application of tranexamic acid to the
      suprapatellar space in the technique where wound closure is performed without
      bleeding control and before the tourniquet is released.

PMID- 30280801
TI  - Diazoxide induces endoplasmic reticulum stress-related neuroprotection mediated
      by p38 MAPK against Abeta25-35 insults.
AB  - OBJECTIVE: The endoplasmic reticulum (ER) -resident caspase-12 was identified as
      a mediator of Abeta neurotoxicity. Recent evidence indicates that mitochondrial
      ATP-sensitive potassium (KATP) channel openers mediate their neuroprotective role
      by adjusting ER stress pathways, but the molecular details remain largely unknown
      and have been investigated. MATERIALS AND METHODS: In this study, the protein
      expression levels of calreticulin (CRT) and caspase-12 activation and
      phosphorylated p38 MAPK were observed by immunoblotting in cultured PC12 cells
      from different groups: treatment with Abeta25-35 (group Abeta25-35), treatment
      with diazoxide (group diazoxide), pretreatment with diazoxide and then exposure
      to Abeta25-35 (group diazoxide + Abeta25-35), pretreatment with p38 MAPK
      inhibitor SB 203580 and then exposure to diazoxide and Abeta25-35 (group SB
      203580 + diazoxide + Abeta25-35), and the control (group control). RESULTS: In
      response to the treatment with Abeta25-35 (10 uM) for 24 h, the protein
      expression levels of CRT and caspase-12 activation were increased and
      phosphorylated p38 MAPK was decreased significantly. Diazoxide reduced CRT
      overexpression and caspase-12 activation and increased the up-regulation of
      phosphorylated p38 MAPK. When SB 203580 was presented before exposure to
      diazoxide and Abeta25-35, CRT expression was markedly suppressed, and the
      inhibition effect of diazoxide on caspase-12 activation was almost eliminated.
      CONCLUSIONS: We showed that diazoxide induced ERS-related neuroprotection
      mediated by p38 MAPK against Abeta25-35 insults. From the clinical point of view,
      these results are of considerable importance for the understanding of AD
      pathogenesis. However, further studies are required to explore more detailed
      mechanisms of the observed effects.

PMID- 30280802
TI  - Octreotide protects doxorubicin-induced cardiac toxicity via regulating oxidative
      stress.
AB  - OBJECTIVE: To explore the role of octreotide in doxorubicin-induced (DOX) cardiac
      toxicity in rats, and to investigate its underlying mechanism. MATERIALS AND
      METHODS: A total of 24 male Sprague Dawley (SD) rats were randomly assigned into
      3 groups, including: the control group (NS group), the DOX-induced cardiac
      toxicity group (DOX group) and the OCT pretreatment + DOX-induced cardiac
      toxicity group (OCT group). Each group had 8 experimental SD rats.
      Electrocardiogram was performed in each rat before and after animal procedure,
      respectively. The serum and heart samples of each rat were collected 10 days
      after the surgical procedure. Cardiomyocyte apoptosis in the myocardial ischemic
      area of rats was determined by hematoxylin and eosin (HE) staining and Terminal
      Deoxynucleotidyl Transferase dUTP Nick-end Labeling (TUNEL) staining. DOX-induced
      oxidative stress was evaluated by detecting the activities of SOD (superoxide
      dismutase), MDA (malondialdehyde), GSH (glutathione), T-AOC (total antioxidant
      capacity) and CAT (catalase). The expression levels of nuclear factor E2 related
      factor-2 (Nrf2), heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1) were
      detected by Western blot and immunohistochemistry. RESULTS: Compared with the NS
      group, heart rate and voltage of QRS wave were both significantly reduced in the
      DOX group, whereas Q-T interval was significantly prolonged (p < 0.05).
      Arrhythmia was even found in some rats of the DOX group. However, rats in the OCT
      group had significantly higher heart rate and voltage of QRS wave, as well as
      shorter Q-T interval when compared with those of the DOX group (p < 0.05). The
      levels of plasma CK-MB and LDH were remarkably lower in the OCT group than those
      of the DOX group. The activities of SOD, GSH, CAT and T-AOC in cardiac homogenate
      of the OCT group were higher than those of the DOX group. However, MDA activity
      and ROS level in cardiac homogenate were remarkably reduced in the OCT group when
      compared with those of the DOX group (p < 0.05). Cardiac pathological lesions
      were alleviated by OCT pretreatment. Moreover, the expression levels of Nrf2, HO
      1 and NQO1 were significantly upregulated in the OCT group than those of the DOX
      group. CONCLUSIONS: Octreotide improves the anti-oxidant capacity of
      cardiomyocytes via activating the Nrf2 pathway, thereby protecting doxorubicin
      induced cardiac toxicity in rats.

PMID- 30280803
TI  - Protective effect of simvastatin on arterial plaque instability induced by p
      cresyl sulfate.
AB  - OBJECTIVE: To study the protective effect of simvastatin on arterial plaque
      instability induced by p-cresyl sulfate (PCS). MATERIALS AND METHODS:
      Apolipoprotein E (ApoE)-/- mice were selected as objects of this study. All mice
      were randomly divided into three groups: 1) the control group, 2) the PCS group
      and 3) the PCS + simvastatin group. After successful modeling, the levels of
      plasma cholesterol, triglyceride, low-density lipoprotein, high-density
      lipoprotein, interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor
      beta (TNF-beta) were detected. The gross specimen of coronary artery was stained.
      Meanwhile, oil red O staining and Sirius red staining were performed for coronary
      arterial sections to observe the lipid and collagen components. The expression
      levels of smooth muscle cells and macrophages were observed by
      immunohistochemistry. In addition, the expression levels of matrix
      metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and
      monocyte chemoattractant protein-1 (MCP-1) in tissues were detected by Western
      blotting. RESULTS: Simvastatin could improve atherosclerotic plaque growth and
      atherosclerotic plaque instability induced by PCS. Moreover, simvastatin could
      also improve the changes of MMPs and TIMPs caused by PCS as well as the
      inflammatory status in mice. CONCLUSIONS: Simvastatin can improve the
      inflammatory status in mice, eventually improving the arterial plaque instability
      caused by PCS.

PMID- 30280804
TI  - Experimental study on application of polypropylene hernia of fat stem cells in
      rats.
AB  - OBJECTIVE: An inguinal hernia is the most common type of external abdominal
      hernia. Normal surgery utilized polypropylene mesh to fix a hernia, but often
      leads to adverse effects including pain and foreign body sensation. Adipose
      derived stem cells are pluripotent stem cells that can be differentiated into
      adipocytes, chondrocytes, skeletal myoblast and osteoblast. The compatibility of
      stem cells with absorbent material mesh or cellular biology mesh has been
      studied. This study investigated the application of adipose-derived stem cells
      coated polypropylene mesh in treating an inguinal hernia. MATERIALS AND METHODS:
      Adipose-derived stem cells were separated and cultured from adipose tissues of SD
      rats. Flow cytometry was utilized to determine antigen subtype including CD90,
      CD34, CD44, and CD45 on the cell surface. Those cells were then induced to be
      differentiated into adipocytes, osteocytes and chondrocytes. Adipose-derived stem
      cells coated polypropylene mesh was then prepared and implanted under a muscular
      layer of rat peritoneal cavity. The occurrence of hematoma and routine blood
      indexes were examined. RESULTS: Adipose-derived stem cells showed attached growth
      with satisfactory proliferation ability. Flow cytometry results showed positive
      rates for CD90, CD44, CD34, and CD45 at 98.2% +/- 1.4%, 97.6% +/- 2.3%, 54.3% +/-
      6.3%, and 13.4% +/- 4.2%, respectively. Adipose-derived stem cells had the
      potency of differentiation. The application of novel mesh decreased macrophage
      number and lymphocytes (p < 0.01) but not leukocytes or neutrophils (p > 0.05).
      CONCLUSIONS: Adipose-derived stem cells coated polypropylene mesh can decrease
      the inflammation post inguinal hernia and can be used as one novel biomaterial in
      treating an inguinal hernia.

PMID- 30280805
TI  - Efficacy of romiplostim in the treatment of ITP in children: a meta-analysis.
AB  - OBJECTIVE: We aimed to analyze the efficacy and safety of romiplostim in the
      treatment of primary immune thrombocytopenia (ITP) in children. MATERIALS AND
      METHODS: PubMed, the Cochrane Database of Systematic Reviews, the Cochrane
      Central Register of Controlled Trials, Chinese biomedical literature database
      (CBM), Chinese Journal Full Text Database (CNKI), Wanfang and VIP database were
      searched. The bibliography was screened according to the inclusion and exclusion
      criteria and the target literature was selected. The data were extracted, and the
      quality of included literature was evaluated. RevMan 5.3 software was used to
      carry out the meta-analysis. The rate of effective, adverse and bleeding events
      was collected, and meta-analysis was performed. RESULTS: 3 out of 43 papers met
      the inclusion criteria. Meta-analysis showed that there was a statistical
      significance in effective rate and median time to platelet rise to response
      criteria of in romiplostim group, RR=5.05, [95% CI (2.21, 11.53), p<0.01] and
      RR=9.67, [95% CI (1.89, 49.46), p<0.01]. Similar results occurred in the rate of
      adverse event and serious adverse event, [RR=0.95, 95% CI (0.69,1.31), p>0.05]
      and [RR=1.65, 95% CI (0.53,5.31), p>0.05]; bleeding event of the two groups was
      similar [RR=1.27, 95% CI (0.92,1.75), p>0.05]. CONCLUSIONS: On the aspect of
      treating ITP, romiplostim is more effective and safer than placebo.

PMID- 30280806
TI  - Research on the protective effects of antioxidants on metabolic syndrome induced
      by thyroid dysfunction.

PMID- 30280807
TI  - FGF23 promotes renal interstitial fibrosis by activating beta-catenin.

PMID- 30280808
TI  - [Spectral Study of LaCl3 in Aqueous Solutions].
AB  - In this study, the Raman and fluorescence spectra of LaCl3 solution were studied
      with theoretical calculation and spectroscopic experiments. Based on B3LYP method
      of density functional theory, with the 6-31G(D,P)+Def2-SV (P) based on the group
      level the lanthanum chloride solution of micro cluster structure is calculated.
      The results show that the micro cluster molecules tend to form a 9 coordination
      structure, which verifies the feasibility of the method. Theoretical and
      experimental Raman values are compared to the basic consistent. The addition of
      LaCl(3) leads to the increase of the peak intensity of the Raman spectra in the
      300~600 cm-1 range, which may be caused by the superposition of the La-O
      vibration and the rocking peaks of O-H in aqueous solutions; In the 3 000~4 000
      cm(-1) range, the peak of lanthanum chloride solution is narrow compared with
      water, which may be caused by the stretching vibration of O-H in lanthanum
      hydrate. Fluorescence emission spectra at 350 nm appear obvious new peak, the
      good linearity was obtained between the peak intensity and the concentrations,
      and a rapid method for the quantitative analysis of lanthanum chloride solution
      from the angle of the complex is also realized. On the same basis set level
      calculated fluorescence emission center of clusters, in the range of allowable
      error, the theoretical calculation and the experimental spectra are basically
      consistent, and the new peak of the experimental spectra are identified.

PMID- 30280809
TI  - [INVOLVEMENT OF THE GASTROINTESTINAL TRACT IN RHEUMATIC DISEASES].
AB  - Aim: The aim of the present study was to show different aspects of the
      interrelation between pathology of the gastrointestinal tract and rheumatic
      diseases based on literature rewiev, single-centers data and case reports.
      Materials and methods: First literature review was performed (databases PubMed,
      Medline). Then was analyzed information according presence of gastrointestinal
      disease in 126 patients with axial spondyloarthritis (SpA) and collected case
      reports as illustration the problem. Results: Involvement of the gastrointestinal
      tract in rheumatic diseases in general is characterized by clinical, etiologycal
      and pathogenetic heterogeneity. It was found a few typical combinations: the
      defeat of the digestive tract as one of the clinical manifestations of rheumatic
      disease (hemorrhagic vasculitis, etc.); the defeat of the digestive tract and
      rheumatic disease as equal related conditions (Crohn's disease and ankylosing
      spondylitis); the defeat of the digestive tract as a consequence of long-existing
      inflammation (amyloidosis, esophagus Barrett); gastrointestinal tract involvement
      as complication of treatment of the rheumatic disease (bleeding when using
      nonsteroidal anti-inflammatory drugs); rheumatic disease as a manifestation of
      paraneoplastic syndrome of the digestive tract. The presence of diseases of the
      gastrointestinal tract is established in more than half (58%) patients with axial
      SpA. In the group of patients considered the most frequently met gastritis (15%),
      chronic pancreatitis (15.9%) and chronic cholecystitis (19%). Conclusions:
      Gastrointestinal tract occurs no less than half of the patients with rheumatic
      diseases and may be either primary or secondary to systemic disease. The
      possibility of coexistence of diseases of the gastrointestinal tract and
      rheumatic disease must be taken into account in the course of patient care. In
      some cases, treatment should be carried out together - a gastroenterologist and a
      rheumatologist.

PMID- 30280810
TI  - [ENDOTHELIAL DYSFUNCTION AS A FACTOR OF DEVELOPMENT ISCHEMIC DISORDERS OF
      INTERSTITIAL CIRCULATION IN BILE PERITONITIS].
AB  - In a review article analyzes and summarizes information on the current
      pathogenesis of bile peritonitis. The role of endothelial dysfunction markers, as
      a factor in the development of ischemic disorders interstitial circulation
      contributes to the elucidation of the molecular mechanisms of the pathogenesis of
      peritonitis, including bile peritonitis. This review is an attempt to synthesize
      and analyze accumulated information on the pathogenetic aspects of the
      development of peritonitis, which will optimize the diagnosis, the development of
      methods of prevention and treatment. This study dysfunction of vascular
      endothelium, will provide additional information relevant to the prediction of
      the adaptation of the organism in the syndrome of endogenous intoxication.

PMID- 30280811
TI  - [COMORBIDITY AND POLYMORBIDITY IN ADULTS AND CHILDREN IN THE LIGHT OF THE PROBLEM
      OF NSAID-GASTROPATHY].
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most demanded drugs.
      Paper presents the data review on the drug activity mechanisms, effectiveness,
      safety, and major drug interactions of NSAIDs at co-morbid conditions in
      different age groups, as well as measures of prevention of NSAID-gastropathy,
      which can occur even against the use of small doses of NSAIDs. The existing
      recommendations on the selection of NSAIDs and the complex therapy with drugs of
      this pharmacological group are shown in considering the individual
      characteristics of the patient, the pharmacological properties of drugs, the
      clinical picture of the disease, the presence of risk factors for adverse
      reactions and drug interactions.

PMID- 30280812
TI  - BIOBANKING Grassroots initiative aims to address community health in
      Pennsylvania.

PMID- 30280813
TI  - BABA BOOMERS The future of age-friendly care.

PMID- 30280814
TI  - MACHINE LEARNING Smarter than 21 dermatologists.

PMID- 30280815
TI  - Making your EHR nurse-friendly.

PMID- 30280816
TI  - HIGHER LEARNING Value a core part of med school curriculum.

PMID- 30280817
TI  - A HIP JOINT Three questions with: Louis Shapiro.

PMID- 30280818
TI  - HOSPITALS AGAINST VIOLENCE.

PMID- 30280819
TI  - How Hospitals Can Better Manage Energy Use.

PMID- 30280820
TI  - The Rapidly Evolving Role of NURSE EXECS.

PMID- 30280821
TI  - 3 Robust Approaches to DEMENTIA CARE.

PMID- 30280822
TI  - Palliative and hospice care design comforts patients, families OFFERING RELIEF.

PMID- 30280823
TI  - Ensuring access to care, regulatory relief top themes.

PMID- 30280824
TI  - Grassroots Innovation.

PMID- 30280825
TI  - My Hospital: Advancing Health in America.

PMID- 30280826
TI  - AVOIDING A FUMBLE That's not a wrap.

PMID- 30280827
TI  - OUT ON A LIMB Two health care top 10 lists for the new year.

PMID- 30280828
TI  - THE BALDRIGE GOES TO... Texas Two-Step.

PMID- 30280829
TI  - MOST WIRED Opt In: Creating a community health record.

PMID- 30280831
TI  - SmnalL,Rural' +Sart Hospitals take advantage of their size and agility to meet
      new health care demands. Still, some worry about their ability to remain
      independent.

PMID- 30280830
TI  - TIME IS BRAIN Pioneers hope mobile stroke unit will help save lives and dollars.

PMID- 30280832
TI  - Hospitals Play 'Exctraordmnary' Role.

PMID- 30280833
TI  - State Medicaid programs are COOKING UP some interesting approaches to reform.

PMID- 30280834
TI  - SERVICE LINE MANAGEET: NOW IT'S CRITICAL Strategies vary, but the goals are the
      same: Control costs, boost quality: improve the patient experience.

PMID- 30280835
TI  - Three Different Paths to Clinical Integration.

PMID- 30280836
TI  - Chitosan-based Nanoparticles in Mucosal Vaccine Delivery.
AB  - Most infectious diseases are caused by pathogenic infiltrations from the mucosal
      tract. Nowadays, the use of vaccines has been widely investigated for the
      prevention of different infectious diseases, infertility, immune disorders,
      malignancies, and allergies. Broad-spectrum adjuvant substances have been studied
      for immune system stimulation with a greater efficiency against specific
      antigens. Various adjuvants have been developed such as inorganic, oil-based, and
      emulsion adjuvants, bacterial products and their derivatives, cytokines, cytosine
      guanine dinucleotide (CpG) motifs, and particulate systems. Mucosal vaccine
      delivery is an alternative route to induce both humoral and cellular immune
      responses. Applying nanoparticles in vaccine formulations allows not only
      improved antigen stability and immunogenicity, but also targeted delivery, and
      consequently, more specific release of the agent of interest. Chitosan
      nanoparticles have immunological activity and mucoadhesive properties. They have
      been used as a mucosal vaccine delivery system for many antigens. This review
      provides an overview of the recent advances in chitosan nanoparticles as a novel
      mucosal vaccine delivery system.

PMID- 30280837
TI  - Development and Evaluation of Real-Time RT-PCR Test for Quantitative and
      Qualitative Recognition of Current H9N2 Subtype Avian Influenza Viruses in Iran.
AB  - Avian influenza H9N2 subtype viruses have had a great impact on Iranian
      industrial poultry production economy since introduction in the country. To
      approach Rapid and precise identification of this viruses as control measures in
      poultry industry, a real time probe base assay was developed to directly detect a
      specific influenza virus of H9N2 subtype -instead of general detection of
      Influenza A viruses- which has been endemic over two last decades in the country.
      An Iranian avian influenza virus strain of A/Iran/chicken/772/1998 H9N2 subtype
      were selected as reference strain for of primers and probe designing. The high
      agreement value of 99% indicated that the devolved real time assay for detection
      of H9 subtype viruses could easily replace the conventional method of virus
      isolation particularly in investigation of viruses like national surveillance
      plan. The limit of detection was almost one EID50 which was the least real
      infectious unit could be detected. So it can be said that this sensitive assay
      provided a powerful tool to not to miss any significant viral biological activity
      neither in the host body nor in the environment. A high level of correlation
      coefficient (R2 = 0.998) also indicated a good correlation between Ct values and
      viral concentrations. , it can be conclude that the real time RT-PCR could be
      easily replace virus isolation in detection of H9N2 influenza viruses especially
      in large monitoring program. The ability in quantifying of the virus
      concentration extends usage of test in more accurate studies.

PMID- 30280838
TI  - Sequencing and In Silico Multi-aspect Analysis of S1 Glycoprotein in 793/B
      Serotype of Infectious Bronchitis Virus Isolated From Iran in 2003 and 2011.
AB  - Infectious bronchitis (IB) is an acute, highly contagious, and economically
      important viral disease of chickens. The S1 subunit from Spike (S) protein plays
      the major role in protective immunity and is involved in the host-virus
      interactions, as well as infectious bronchitis virus (IBV) serotyping. Aim of the
      present study was multi-aspect analysis of the molecular and immunological
      features of 5&#39; part belonging to the S1 glycoprotein sequence of Iranian
      793/B IBV strain isolates. This might ideally help in characterization,
      prevention, and vaccine development. The tissue samples were prepared, followed
      by virus isolation, reverse transcription polymerase chain reaction and
      restriction fragment length polymorphism analysis. In addition, sequencing and
      registration of the sequences in the National Center for Biotechnology
      Information were performed. Moreover, 12 sequences were retrieved from Fars
      province, Iran. The next steps included evaluation of conservation/variability
      along the sequences, phylogenetic analysis, estimation of the average
      evolutionary divergence over all the sequence pairs, predicting the
      phosphorylation/N-glycosylation/palmitoylation sites, and the final analysis of
      antigenicity. The findings of alignment, entropy plot, and pairwise similarity
      analysis revealed 17 hypervariable regions. The isolates belonging to Tehran were
      clustered in phylogenetic tree, and the most similar isolates to them were
      ADW11182 and ADW11183. Location of some of the N
      glycosylation/phosphorylation/palmitoylation points indicated that these sites
      were conserved among the isolates. Furthermore, the frequency of epitopes and
      their scores reflect the high immunogenicity of S1 protein in 793/B serotype.
      Analysis of the primary and secondary structures demonstrated that their
      parameters had variable values and were different regarding the number and
      location of &alpha;-helix, &beta;-strand, and coils. According to our findings,
      the Iranian isolates of 793/B serotype change their molecular characteristics
      during time and in different geographical regions. These alterations might
      account for failure in prevention programs and differences in virulence and
      pathogenicity.

PMID- 30280839
TI  - Design and Production of a Novel Recombinant Chimeric IL2-Omp31 Antigen against
      Brucella Infection.
AB  - Brucellosis is a zoonotic disease in human and animals. Brucella melitensis is
      one of the most pathogenic species of Brucella in goat and sheep. Omp31 is an
      outer membrane protein of Brucella that acts as an immunogenic protein. Cytokines
      are glycoproteins with low molecular weight that play the role of an immune
      adjuvant and regulate immune responses. Interleukin-2 is one of the most
      important cytokines, which are secreted by the white blood cells and involved in
      T cell immune responses. In the present study, a chimeric Omp31-Interleukin2
      recombinant protein was generated by means of genetic engineering techniques.
      This chimeric coding sequence was amplified by using specific primers and using
      Splicing Overlap Extension (SOE) PCR technique. The fusion of the two mentioned
      proteins was accomplished using a rigid linker. The generated chimeric IL2-Omp31
      fragment was TA cloned, and then subcloned into pEt22b vector as an expression
      vector. The chimeric protein was successfully expressed in E. coli BL21 (DE3) and
      confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      and also Western-blotting analysis. Finally, in order to assess the antigenic
      features of the recombinant chimeric IL2-Opm31 protein, its secondary structure
      and antigenicity were predicted in silico.

PMID- 30280841
TI  - A Serological Survey of Neospora caninum Infection in Urban and Rural Dogs in
      Ahvaz District, Southwest of Iran.
AB  - Dogs are important in the epidemiology of Neospora caninum because they act as
      definitive hosts, shedding oocysts in the environment. The aim of the present
      survey was to evaluate the serological prevalence of Neospora caninum infection
      in urban and rural dogs in Ahvaz district, southwest of Iran. In this study,
      blood samples were taken from 100 rural dogs and 50 urban dogs. The dogs were
      categorized into two age groups (i.e., &le; 3 and > 3 years). Neospora
      agglutination test (NAT) was performed for the detection of infection. Among 150
      samples, 30 (20%) showed infection in 1:50 to 1:800 dilutions by NAT (confidence
      interval 95%: 13.60-26.40). The antibody titers were as follows: 1:50 (n=1),
      1:100 (n=14), 1:200 (n=3), 1:400 (n=10) and 1:800 (n=2). The highest serum
      dilution was 1:100 in 46.67% of the infected dogs and the lowest serum dilution
      was 1:50 in 3.33% of them. The obtained results showed a significant difference
      in seroprevalence between urban (10%) and rural (25%) dogs (P=0.03). Although the
      seroprevalence was higher in dogs above three years of age (23.33%) than below
      three years (17.78%), there was not a significant difference among different age
      groups in this regard (P>0.05). The possibility of infection in dogs above the
      age of three years was 1.3 more than those below three years of age (confidence
      interval 95%: 0.58-2.9). It can be concluded that a relatively considerable
      percentage of dogs in Ahvaz district are infected with N. caninum. These infected
      dogs can play an important role in the transmission of neosporosis to other
      animals.

PMID- 30280842
TI  - Comparative Evaluation of the Biochemical Effects of Ketamine plus Ketoprofen and
      Midazolam in the Premedication of Pigeons.
AB  - The present study was conducted with the aim of comparing the effects of
      premedication with ketoprofen and midazolam in birds. A total of 24 male pigeons
      with an approximate weight of 300 g were divided into four equal groups. The
      control group (Group I) was injected with ketamine alone. Groups II-IV were
      injected with ketoprofen alone, ketoprofen+ketamine, and midazolam+ketamine,
      respectively. The biochemical changes in the four groups were evaluated after
      intramuscular drug injections at different anesthetic levels. A record of
      biochemical changes was maintained for each group. Blood samples were taken
      before and after the administration of the medications in order to measure the
      levels of serum alkaline phosphatase (ALP), oxaloacetate transaminase (OT),
      prothrombin time (PT), glucose (GLU), lactate dehydrogenase (LDH), albumin (Alb),
      total protein (TP), and gamma-glutamyl transferase (GGTF). The results showed
      significant differences in the mean levels of ALP, OT, PT, GLU, LDH, Alb, and TP
      after anesthesia, compared to that before anesthesia. Therefore,
      ketoprofen+ketamine can be used for the induction of anesthesia in birds.The
      present study was conducted with the aim of comparing the effects of
      premedication with ketoprofen and midazolam in birds. A total of 24 male pigeons
      with an approximate weight of 300 g were divided into four equal groups. The
      control group (Group I) was injected with ketamine alone. Groups II-IV were
      injected with ketoprofen alone, ketoprofen+ketamine, and midazolam+ketamine,
      respectively. The biochemical changes in the four groups were evaluated after
      intramuscular drug injections at different anesthetic levels. A record of
      biochemical changes was maintained for each group. Blood samples were taken
      before and after the administration of the medications in order to measure the
      levels of serum alkaline phosphatase (ALP), oxaloacetate transaminase (OT),
      prothrombin time (PT), glucose (GLU), lactate dehydrogenase (LDH), albumin (Alb),
      total protein (TP), and gamma-glutamyl transferase (GGTF). The results showed
      significant differences in the mean levels of ALP, OT, PT, GLU, LDH, Alb, and TP
      after anesthesia, compared to that before anesthesia. Therefore,
      ketoprofen+ketamine can be used for the induction of anesthesia in birds.

PMID- 30280840
TI  - Antimicrobial Susceptibility Profile of Enterococcus Species Isolated from
      Companion Birds and Poultry in the Northeast of Iran.
AB  - Enterococci are Gram-positive facultative anaerobic bacteria commonly found in
      the gastrointestinal tract of the mammals and birds. These cocci are isolated
      from urinary tract infections, bacteremia, endocarditis, and burn wounds in
      humans. The evolution of antibiotic-resistant enterococci raised a problem due to
      the possibility of the transmission of these organisms between poultry and human.
      Regarding this, the present study was conducted to evaluate the prevalence of
      Enterococcus species among companion birds and poultry in the Northeastern of
      Iran and determine the antibiotic susceptibility profile of enterococci. To this
      end, oral and cloacal swabs were collected from 150 caged birds. Antibiotic
      susceptibility profile was determined using the standard disk diffusion method.
      The results revealed that out of 150 samples, 56 (37.33%) cases contained
      enterococci. Most of the specimens (25.33%) were Enterococcus faecalis isolated
      from 6.66% of the samples. Additionally, 2.66% and 1.33% of the samples were
      contaminated with Enterococcus mundtii and Enterococcus gallinarum, respectively.
      Furthermore, Enterococcus malodoratus and Enterococcus raffinosus were isolated
      from 0.66% of the samples. The results revealed that all of the isolates of E.
      faecalis and E. faecium were resistant to more than five antimicrobial agents.
      Most of E. faecalis and E. faecium isolates showed resistance to Cefazolin,
      Tiamulin, Flumequine, and Cephalexin. Accordingly, the majority of the isolates
      had multidrug resistance to the tested antibiotics. In conclusion, the presence
      of multidrug-resistant enterococci in the birds living close to humans requires
      thorough observations due to the transmission of these organisms to humans.

PMID- 30280843
TI  - Bioinformatics Analysis of Upstream Region and Protein Structure of Fungal
      Phytase Gene.
AB  - Phytase increases the bioavailability of phytate phosphorus in seed-based animal
      feeds and reduces the phosphorus pollution of animal waste. Since most animal
      feeds for pellets are heated up to 65-80 &deg;C, the production of a thermostable
      structure for phytase can be useful. In this study, we sought to perform
      bioinformatics analysis of the upstream region and protein structure of fungal
      phytase to improve its expression and thermostability properties. We used
      bioinformatics methods such as similarity search, multiple alignment, statistical
      analysis of physicochemical properties of amino acids, pattern recognition, and
      protein modeling to find out the effective factors in heat resistance of phytase.
      Change in Gibbs free energy (&Delta;G) of the best pattern promoter resulting
      from the interaction between RNA polymerase and the promoter sequences of
      modified genes of phytase was equal to -9 kcalmol-1, which is lower compared to
      other interactions. The evaluation of the three-dimensional structure of new
      phytases showed that amino acid substitutions aimed at improving thermostability
      did not change the form and structure of the protein. The results of Prochek,
      Whatcheck, and ERRAT for structural analysis and verification were 84, 72, and
      70, respectively, that were satisfactory.

PMID- 30280844
TI  - Diagnosis of Avian Mycoplasmas: A Comparison between PCR and Culture Technique.
AB  - Mycoplasma gallisepticum and Mycoplasma synoviae are the causative agents of
      avian mycoplasmosis in commercial poultry. Among the available tools, polymerase
      chain reaction (PCR) and culture are confirmatory tools for the diagnosis of
      mycoplasmosis after the initial serological screening of suspected birds.
      Overall, 181 samples were analyzed, 152 (84%) and 103 (57%) of which were found
      positive by PCR and culture, respectively. Further, 54 (92%) broiler samples were
      found positive for general avian mycoplasma. Among the total positive samples, MS
      positivity was as high as 72 (47%) by PCR, while it was 45 (44%) by culture. MG
      positivity was 23% and 25% in PCR- and culture-positive samples. MG grows more
      easily compared to MS. The agreement value between the tests was 67%. Overall,
      flock wise prevalence was not much varied. The prevalence of mycoplasmosis was
      higher during winter. Our study confirmed that PCR is the most sensitive and
      reliable tool for the diagnosis of avian mycoplasmosis in field samples.

PMID- 30280845
TI  - [Efficient Polymer Solar Cells Using ZnO Electron Transporting Layer with Layered
      Magentron Sputtered ZnO Film and/or Modified with Functionalized Carbon
      Nanopartilces].
AB  - Polymer solar cells (PSCs) with ZnO electron transporting layer has been widely
      studied because ZnO has superior electron transport capability and high light
      transmittivity. However, lots of defects existed in ZnO film fabricated with sol
      gel method and vacuum sputtering deposition can greatly increase carrier
      recombination at the ZnO interface. Therefore, it is important to enhance the
      performance of PSCs to inhibit defects and improve contact quality of ZnO
      interface. The regioregular poly(3-hexylthiophene) (P3HT) and 6,6-phenyl C61
      butyric acid methylester (PCBM) based inverted PSCs with ZnO electron
      transporting layer have been developed by using layered magnetron sputtered ZnO
      and/or ionic liquid functionalized carbon nanopartilces (ILCNs) modification. The
      power conversion efficiencies (PCEs) of PSCs with ZnO layer sputtered with Ar and
      Ar/O(2) gas are 2.2% and 2.8%, respectively. PSCs modified with ILCNs or layered
      sputtered ZnO can respectively reach 3.4% and 3.1%, and further up to 3.8% using
      layered sputtered ZnO and ILCNs integrated modification. PSCs using modified ZnO
      layer show the vanishment of negative capacitive behavior, lowering reverse dark
      current and better diode characteristics. The results indicated that using
      layered sputtered ZnO or ILCNs, or both integrated modification can efficiently
      inhibit the defects of ZnO interface and improve contact quality ZnO/P3HT?PCBM
      interface. However, this integrated modification method is a more efficient
      strategy to enhance ZnO layer electron transporting and extraction capabilities,
      and further improve PCEs of PSCs.

PMID- 30280846
TI  - [THE USE OF REMAXOL IN THE TREATMENT OF METABOLIC SYNDROME IN PATIENTS WITH
      NONALCOHOLIC STEATOHEPATITIS AND DIABETES MELLITUS 2 TYPE].
AB  - Aim: The aim of the study was to assess the effectiveness of the inclusion in the
      scheme remaxol treatment of metabolic syndrome in patients with nonalcoholic
      steatohepatitis and diabetes mellitus 2 type. Materials and methods: Data of 76
      patients with metabolic syndrome in a non-alcoholic steatohepatitis and type 2
      diabetes were analyzed. Patients were randomized by gender and age, and are
      divided into 2 groups according to the scheme of therapy: patients in group I
      (major - 38) conducted a basic therapy in combination with remaxol: intravenous
      infusion of 400 ml of 1 times a day for 10 days, group II patients (comparison -
      38) combined basic therapy with intravenous ademetionine: 400 mg, in a solution
      diluted NaCL 0,9% 400 ml 1 time per day for 10 days. In addition to standard
      clinical and laboratory tests were studied biochemical parameters of liver
      activity, lipid and carbohydrate metabolism in the dynamics: before therapy and
      after its completion. Results: It was found that the inclusion in the scheme of
      drugs from the group of succinates (remaxol) reduces the severity of metabolic
      syndrome by reducing the manifestations of cholestasis and cytolysis, and
      improving lipid and glucose metabolism. As a result, significantly reduced the
      severity of the main clinical syndromes: asthenovegetative 46% and dyspeptic
      syndromes - 46% and 15%, respectively.

PMID- 30280848
TI  - [METHODOLOGICAL FEATURES OF THE pH-METRY IN PATIENTS WITH A COMBINATION OF
      GASTROESOPHAGEAL REFLUX DISEASE AND BRONCHIAL ASTHMA].
AB  - Conducting daily pH monitoring in patients with asthma has a number of features.
      Due to the fact that the introduction of the pH probe in such patients may
      provoke an asthma attack, necessary pre-treatment of the patients to the study.
      It is necessary to perform the procedure for achieving remission of asthma
      medication. Utility of the modified pH measuring techniques (prolonged, 48-hour)
      is the need to identify pathological gastroesophageal reflux in patients with
      asthma and evaluate the effectiveness of antisecretory drugs, allowing for
      improved asthma, increasing the period of remission, and to improve the quality
      of life of patients.

PMID- 30280849
TI  - [THE EFFICIENCY OF SCHOOL OF COMBINED PATHOLOGY IN THE REHABILITATION OF PATIENTS
      WITH PEPTIC DUODENAL ULCER ASSOCIATED WITH ARTERIAL HYPERTENSON AFTER ACUTE
      GASTROINTESTINAL BLEEDING].
AB  - Objectives of the investigation was to examine the dynamics of emotional and
      autonomic disorders in patients with peptic duodenal ulcer (DU) associated with
      arterial hypertension after acute gastrointestinal bleeding during training at
      School of Combined Pathology (SCP). Main group included 25 patients. The
      comparison group consisted of 26 patients with the matched pathology, sex and
      age, but not trained at SCP. Results. Both groups of patients demonstrated
      improvement in emotional sphere and autonomic regulation. However, in patients
      who had training at the SCP the indicators of emotional status improved earlier
      and got a greater extent. Optimization of autonomic regulation was identified in
      3 months, not six months, like in untrained patients. Conclusion. Training
      hypertensive patients with peptic DU at the SCP improves the efficiency of
      emotional state and autonomic regulation.

PMID- 30280850
TI  - [GUT AND VAGINAL MICROBIOTA IN FEMALE WITH REPRODUCTIVE DISORDERS ASSOCIATED WITH
      GASTROINTESTINAL DISTURBANCE].
AB  - The aim of research - a comparative study of the microflora of the vagina and
      bowel in women with secondary infertility and gastrointestinal distress.
      Materials and methods. We examined gut and vaginal microbiota in 17 infertile
      women according to the presence or absence of gastrointestinal diseases. We used
      a standard procedure for microbiological examination. Results. Certain changes of
      bacterial load and composition in both reservoirs were established. They allowed
      us to conclude the same trends in characterizing of the developing dysbiosis.
      Conclusion. Thus, the simultaneous studying of vaginal and gut microflora seems
      to be rational during the examination of women with childbearing disorders. It
      could possibly increase the treatment efficacy and/or prevent the development of
      some pathology.

PMID- 30280851
TI  - [GASTROENTEROLOGICAL MASK OF CARDIOVASCULAR DISEASE].
AB  - The article presents variants of the course of cardiovascular disease under a
      clinical mask of gastroenterological diseases. The author analyzes the clinical
      examples of atypical symptoms, discusses the diagnostic errors and shows ways to
      prevent them.

PMID- 30280852
TI  - [CURRENT ISSUES IN THE CHOICE OF ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH
      METABOLIC SYNDROME AND RELATED NON-ALCOHOLIC FATTY LIVER DISEASE].
AB  - Widespread in clinical practice, comorbid conditions and diseases, among which is
      the high prevalence of metabolic syndrome (MS), determine the need for selection
      of the optimal pharmacotherapy. The presence of certain liver diseases, including
      nonalcoholic fatty liver disease (NAFLD), may interfere with the processes of
      transformation of drugs, the metabolism of which occurs in the liver, which has
      been proved by experimental investigations. The article deals with the rational
      choice of antihypertensive drugs as a whole, and angiotensin-converting enzyme
      (ACE) in particular in patients with metabolic syndrome and NAFLD. Particular
      attention is paid to the possibilities of certain ACE inhibitors and their
      pharmacological properties.

PMID- 30280853
TI  - Calculated decisions: sequential organ failure assessment (SOFA) score
AB  - The SOFA score predicts mortality risk for patients in the intensive care unit
      based on lab results and clinical data.

PMID- 30280854
TI  - Calculated decisions: qSOFA (quick SOFA) score for sepsis
AB  - The qSOFA score identifies patients with suspected infection who are at high risk
      for in-hospital mortality outside of the intensive care unit.

PMID- 30280855
TI  - Putting Our Best-Protected Feet Forward.

PMID- 30280856
TI  - Proven Methods for Reducing Noise Exposures.
AB  - Noise dosimetry may be necessary if the workplace noise levels vary throughout
      the day or if the workers are mobile, driving vehicles, or working in areas where
      it is either unsafe or impractical for a sound level meter to be used.

PMID- 30280857
TI  - Can You Hear the Training Now?
AB  - There is no correct, best, or worst training effort. The main things to remember
      are consistency and repetition. Any information has to be repeated in order for
      us to actually remember and put it to use.

PMID- 30280858
TI  - Selecting Hearing Protectors--It's the Fit That Counts.
AB  - In addition to selecting HPDs and documenting the PAR achieved by each worker,
      hearing protector fit testing is a critical component to worker training.

PMID- 30280859
TI  - Our Anaheim Excursion.
AB  - Get ready for 2016's biggest U.S. safety show by viewing dozens of the new
      products exhibitors will be displaying.

PMID- 30280860
TI  - Basics of Indoor Air Quality in the Workplace.
AB  - OSHA suggests that a proactive approach be taken to address IAQ concerns. Failure
      to respond expeditiously and effectively to IAQ concerns can quickly lead to more
      numerous or serious adverse health issues.

PMID- 30280862
TI  - The Affordable Care Act's Impact on Small Business.
AB  - Issue: Small-business owners have seen significant gains in health care coverage
      for themselves and their employees thanks to the Affordable Care Act. Though
      efforts to repeal the law failed in 2017, the current administration continues to
      take steps that undermine the law's progress. In recent months, new rules have
      been announced that allow more groups to establish association health plans and
      extend the length of short-term health insurance plans. These changes are likely
      to impact the stability of the marketplaces and coverage rates for the small
      business community. Goal: Examine the Affordable Care Act's impact on small
      businesses, solo entrepreneurs, and small-business employees. Methods: Analysis
      of ACA small-business enrollment data from established sources, including federal
      agencies and nonpartisan health care research foundations, supplemented by
      analysis of U.S. Census data. Findings and Conclusions: Because of the creation
      of the individual marketplaces and the expansion of Medicaid, more entrepreneurs
      and small-business employees have health coverage than before the ACA was
      implemented. Indeed, the uninsured rate for small-business employees fell by
      almost 10 percentage points post-ACA. The ACA also has helped stabilize health
      costs for many small businesses that provide coverage, with the rate of small
      business premium increases falling by half following implementation of the law.

PMID- 30280861
TI  - Sick Building Syndrome: What It Is and Tips for Prevention.
AB  - Telltale clues include increased absenteeism, a large number of occupants
      complaining about vague but similar symptoms, and a common history of symptom
      resolution when people are not in the building.

PMID- 30280863
TI  - Creating an Effective Ergonomics Program.
AB  - With the right assessment, training, management support, and processes in place,
      you can proactively identify and eliminate ergonomic issues before they result in
      debilitating injuries.

PMID- 30280864
TI  - Maintaining Drug-Free Workplaces Where Marijuana is Legal.
AB  - How much marijuana (or THC) should be allowable? This is an extremely difficult
      question and is asked of the drug testing industry regularly.

PMID- 30280865
TI  - How to Maintain a Drug-Free Workplace and Ensure Audit Success.
AB  - Our drug-free workplace program should also get a checkup every year. Laws and
      regulations may have changed, and the company may need to adjust its policies and
      procedures.

PMID- 30280866
TI  - Transscrotal orchidopexy for palpable cryptorchid testis: follow-up and outcomes.
AB  - We retrospectively reviewed the results of transscrotal orchidopexy in the
      surgical management of palpable testis. From January 2014 to June 2017, 130 male
      children with a total of 140 palpable undescended testes (UDT) underwent
      transscrotal orchidopexy. The charts were retrospectively reviewed for
      demographic data, preoperative position and mobility of the testis, patency of
      the peritoneal vaginal duct (PVD), and post-operative complications. The resting
      position of the testis and its traction towards the scrotum were assessed before
      surgery and under anaesthesia. The mean age of the patients was 4.6 years. The
      position of the testis assessed at surgery was in most cases at the external
      inguinal ring (62.8%), at the neck of the scrotum (15.7%), in the inguinal canal
      (12.8%), or in an ectopic position (8,5%). A PVD was found in 66 testes (47.1%).
      Two surgical cases required an inguinal incision. In each patient, the
      postoperative course was unremarkable. The testicle at 1-year follow-up was in a
      scrotal position in 134 cases, but 6 patients required a second surgical
      intervention for re-ascent of the testis. No testicular atrophy or inguinal
      hernias were observed. Transscrotal orchidopexy is a simple and effective
      procedure for the treatment of palpable UDT. The incidence of complications is
      low and manageable, with rapid postoperative recovery and early resumption of
      normal activities.

PMID- 30280867
TI  - Fork Truck Free and New Materials Handling Innovations.
AB  - The ergonomic answer to moving heavy items without a fork truck, this innovative
      approach is designed for ease of use, higher productivity, and keeping workers on
      the job and free from injuries.

PMID- 30280868
TI  - Points & Pearls: Updates and controversies in the early management of sepsis and
      septic shock
AB  - Sepsis is a common and life-threatening condition that requires early recognition
      and swift initial management. Diagnosis and treatment of sepsis and septic shock
      are fundamental for emergency clinicians, and include knowledge of clinical and
      laboratory indicators of subtle and overt organ dysfunction, infection source
      control, and protocols for prompt identification of the early signs of septic
      shock. [Points & Pearls is a digest of Emergency Medicine Practice.]

PMID- 30280869
TI  - OSHA Guidelines, Incentives, and the Win-Win-Win-Win Scenario.
AB  - Improving employee engagement will greatly enhance the effectiveness of your
      safety training and meetings, increase participation in voluntary programs,
      improve two-way communications between employer and employee, and raise morale
      companywide.

PMID- 30280870
TI  - Points & Pearls: Diagnosing and managing common genital emergencies in pediatric
      girls
AB  - The presentation of genital injuries and emergencies in pediatric girls can
      sometimes be misleading. A traumatic injury with excessive bleeding may be a
      straddle injury that requires only conservative management, while a penetrating
      injury may have no recognizable signs or symptoms but require extensive surgery.
      This issue reviews the most common traumatic genital injuries in girls presenting
      to the emergency department, including straddle injuries, hematomas, and
      impalement injuries. Nontraumatic emergencies, including hematocolpos and
      urethral prolapse, are also discussed. Evidence-based recommendations are
      presented for identifying and managing these common genital injuries and
      emergencies in pediatric girls. [Points & Pearls is a digest of Pediatric
      Emergency Medicine Practice.]

PMID- 30280871
TI  - Safety Incentive and Reward Programs Can Help Increase Work Safety.
AB  - Ultimately, one of the keys to ensuring job satisfaction and happiness in the
      workplace is by celebrating your employees' achievements.

PMID- 30280872
TI  - A Standardized Process to Determine Appropriate and Effective Placement of
      Automated External Defibrillators.
AB  - The new tool is an innovative, standardized method of determining the most
      effective placement of these necessary devices.

PMID- 30280873
TI  - Your Heart: The Differences Between Sudden Cardiac Arrest and a Heart Attack.
AB  - Eating healthy, regularly exercising, and generally looking after the body are
      the best ways to reduce your chances of suffering a heart attack or an SCA.

PMID- 30280874
TI  - A Comprehensive Look at the FAST Act.
AB  - The law mandates that FMCSA provide recognition for motor carriers that make
      voluntary use of advanced technologies and enhanced driver fitness measures.

PMID- 30280875
TI  - Prevent Future Profits From Going 'Down the Crack'.
AB  - Nearly all leaks, overflows, broken lines/hoses, etc. involve chemicals/oils that
      should not get into our streams and drinking water sources.

PMID- 30280876
TI  - Protecting Our Future: Young Worker Safety on the Job.
AB  - Encourage young workers to ask questions about tasks or procedures that are
      unclear or not understood.

PMID- 30280877
TI  - Rethinking Safety Excellence.
AB  - Great performers are able to demonstrate the ability to win over and over again.

PMID- 30280878
TI  - Discovering Safety: Why Participation Does Not Equal Engagement.
AB  - Solely broadcasting "shoulds" and "have-tos" quashes energy and internal
      motivation.

PMID- 30280879
TI  - Hand Hygiene When Being Potentially Exposed to Heavy Metal Dust.
AB  - It is important to recognize that hand washing cannot replace safe and hygienic
      work practices and the use of personal protective equipment when handling heavy
      metal-containing materials.

PMID- 30280880
TI  - More Than Barrier Protection, Single-Use Gloves Manage Skin Health.
AB  - Skin health can be compromised from a continued cycle of hands going from a warm,
      wet glove interior to the rapid drying caused by evaporation when gloves are
      removed, and then back again.

PMID- 30280881
TI  - Real Threat or False Alarm: Aare You Prepared for the Next Time the Fire Alarm
      Sounds?
AB  - Each type of alarm requires its own unique response, and a fire alarm is no
      different.

PMID- 30280882
TI  - Getting Ready for Emergencies.
AB  - The Plan-Do-Check-Act model, which both DHS and FEMA use, really helps when
      implementing and practicing your emergency plans.

PMID- 30280883
TI  - Six Tips to Improve Your Lockout/Tagout Program.
AB  - A program that encourages communication can identify strengths and weaknesses
      much more efficiently than a program that remains static and unchanging after
      initial training.

PMID- 30280884
TI  - Biological Activation of Bioinert Medical High-Performance Oxide Ceramics by
      Hydrolytically Stable Immobilization of c(RGDyK) and BMP-2.
AB  - High-performance oxide ceramics (HPOC), such as alumina, zirconia, and dispersion
      ceramics thereof are successfully used as articulating components in joint
      arthroplasty. HPOC exhibit excellent wear resistance, high strength, and
      cytocompatible behavior; however, they lack sufficient tissue bonding capability.
      Thus, they are primarily deployed as low-wear-bearing articulating components in
      arthroplasty without direct tissue contact, although proper cellular stimulation
      would hold significant advantages. Here, we describe a surface modification
      approach for HPOC, enabling hydrolytically stable interfacial binding of c(RGDyK)
      peptides and BMP-2 proteins to significantly improve the adhesion and osteogenic
      differentiation of human mesenchymal stem cells (hMSCs) without altering the
      mechanical properties of the underlying ceramic substrates. Analyses of cellular
      attachment of murine fibroblasts (L929), human alveolar basal epithelial cells
      (A549), hMSCs on c(RGDyK), and osteogenic differentiation of hMSCs on BMP-2
      coated interfaces demonstrate significant improvements of cell adhesion and an
      enhanced osteogenic differentiation potential in vitro. The presented approach
      provides a strategy for the development of a novel class of bioactive HPOC with
      osseointegration potential that could lead to novel therapeutic solutions for
      biomedical applications. Furthermore, the developed surface modification is
      designed in a way to be readily translated to other medically employed bioinert
      materials in the future.

PMID- 30280885
TI  - High Throughput, Direct Determination of 226Ra in Water and Digested Geological
      Samples.
AB  - A method was developed for direct measurements of 226Ra in water samples with
      triple quadrupole inductively coupled plasma mass spectrometry (ICP-QQQ). The
      limit of detection was 0.42 pg L-1 226Ra (15 mBq L-1, 0.42 pCi L-1), which is
      compliant with the specifications for methods used for routine analysis of
      drinking water quality according to European and U.S. regulations. The use of N2O
      as reaction gas ensured that no separation before analysis was necessary. Water
      samples with high total dissolved solids (conductivity >100 mS cm-1) were also
      successfully analyzed after a simple dilution, yet the associated detection limit
      was higher (17 pg L-1, 0.61 Bq L-1, 16 pCi L-1). 226Ra content in soil and rock
      samples was determined with the same method after acid (HNO3 + H3PO4) digestion
      and dilution, resulting in a limit of detection of 0.75 ng kg-1 (27 Bq kg-1, 0.74
      nCi L-1). Analysis of water samples was achieved within 2 min on a running
      instrument, while the preparation and analysis of 15 geological samples can be
      completed in 3 h. The key advantages of this direct analysis method are short
      preparation time, low labor intensity, low sample input (2 mL for water samples,
      0.2 g for geological material), high sample throughput (2 min sample to sample,
      >150 samples measured in 8 h), and use of standard ICP-QQQ hardware. Overall, the
      proposed method offers a new opportunity for measuring a large number of samples
      with minimal effort and, in turn, for improving emergency preparedness,
      environmental monitoring, and data collection for environmental modeling.

PMID- 30280887
TI  - Comment on "Wavelength-Resolved Photon Fluxes of Indoor Light Sources:
      Implications for HO x Production".

PMID- 30280886
TI  - Quantifying Surface Temperature of Thermoplasmonic Nanostructures.
AB  - Precise measurement of the temperature right at the surface of thermoplasmonic
      nanostructures is a grand challenge but extremely important for the photochemical
      reaction and photothermal therapy. We present here a method capable of measuring
      the surface temperature of plasmonic nanostructures with surface-enhanced Raman
      spectroscopy, which is not achievable by existing methods. We observe a sensitive
      shift of stretching vibration of a phenyl isocyanide molecule with temperature
      (0.232 cm-1/ degrees C) as a result of the temperature-dependent molecular
      orientation change. We develop this phenomenon into a method capable of measuring
      the surface temperature of Au nanoparticles (NPs) during plasmonic excitation,
      which is validated by monitoring the laser-induced desorption process of the
      adsorbed CO on Au NP surface. We further extend the method into a more demanding
      single living cell thermometry that requires a high spatial resolution, which
      allows us to successfully monitor the extracellular temperature distribution of a
      single living cell experiencing cold resistance and the intracellular temperature
      change during the calcium ion transport process.

PMID- 30280888
TI  - Structural Characterization of Acidic Compounds in Pyrolysis Liquids Using
      Collision-Induced Dissociation and Fourier Transform Ion Cyclotron Resonance Mass
      Spectrometry.
AB  - In this study, a novel approach to characterize and identify acidic oil compounds
      utilizing the fragmentational behavior of their corresponding precursor ions is
      presented. Precursor ions of seven analyzed pyrolysis oils that were generated
      from pyrolysis educts of different origins and degrees of coalification were
      produced by electrospray ionization in the negative ion mode (ESI(-)). Following
      a fragmentation of all ions in the ion cloud by collision-induced dissociation
      (CID), the precursor and product ions were subsequently detected by ultrahigh
      resolving Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR
      MS). The ESI(-)-CID data sets were evaluated by applying either a targeted
      classification or untargeted clustering approach. In the case of the targeted
      classification, 10% of the ionized precursor ions of the analyzed pyrolysis
      liquid samples could be classified into one of 11 compound classes utilizing
      theoretical fragmentation pathways of these classes. In contrast, theoretical
      fragmentation pathways were not necessary for the untargeted clustering approach,
      making it the more transmittable method. Results from both approaches were
      verified by analyzing standard compounds of known structure. The analysis and
      data evaluation methods presented in this work can be used to characterize
      complex organic mixtures, such as pyrolysis oils, and their compounds in-depth on
      a structural level.

PMID- 30280889
TI  - Reduction and Increase in Thermal Conductivity of Si Irradiated with Ga+ via
      Focused Ion Beam.
AB  - Focused ion beam (FIB) technology has become a valuable tool for the
      microelectronics industry and for the fabrication and preparation of samples at
      the micro/nanoscale. Its effects on the thermal transport properties of Si,
      however, are not well understood nor do experimental data exist. This paper
      presents a carefully designed set of experiments for the determination of the
      thermal conductivity of Si samples irradiated by Ga+ FIB. Generally, the thermal
      conductivity decreases with increasing ion dose. For doses of >1016 (Ga+/cm2), a
      reversal of the trend was observed due to recrystallization of Si. This report
      provides insight on the thermal transport considerations relevant to engineering
      of Si nanostructures and interfaces fabricated or prepared by FIB.

PMID- 30280890
TI  - Posttranslational Chemical Mutagenesis: To Reveal the Role of Noncatalytic
      Cysteine Residues in Pathogenic Bacterial Phosphatases.
AB  - The field of chemical site-selective modification of proteins has progressed
      extensively in recent decades to enable protein functionalization for imaging,
      drug delivery, and functional studies. In this Perspective, we provide detailed
      insight into an alternative use of site-selective protein chemistry to probe the
      role(s) of unpaired Cys residues in the structure and function of disease
      relevant proteins. Phosphatases are important players in the successful infection
      of pathogenic bacteria, which represent a significant health burden, particularly
      in multi-drug-resistant strains. Therefore, a strategy for readily probing the
      key amino acid role(s) in structure and function may facilitate the targeting and
      inhibition of these virulence factors. With a dehydroalanine-based
      posttranslational chemical mutagenesis approach, it is possible to reveal
      hitherto unknown function(s) of noncatalytic Cys residues and confirm their role
      and interplay in pathogenic bacterial phosphatases. By selectively modifying
      reactive sulfhydryl side chains in different protein local environments, this
      posttranslational site-selective chemical mutagenesis approach reveals structural
      information about binding pockets and regulatory roles of the modified residues,
      which can be further validated by conventional site-directed mutagenesis.
      Ultimately, these new binding pockets can serve as templates for enhanced
      structure-based drug design platforms and aid the development of potent and
      specific inhibitors.

PMID- 30280891
TI  - Resonant Transport in Single Diketopyrrolopyrrole Junctions.
AB  - We study the single-molecule transport properties of small bandgap
      diketopyrrolopyrrole oligomers (DPP n, n = 1-4) with lengths varying from 1 to 5
      nm. At a low bias voltage, the conductance decays exponentially as a function of
      length indicative of nonresonant transport. However, at a high bias voltage, we
      observe a remarkably high conductance close to 10-2 G0 with currents reaching
      over 0.1 MUA across all four oligomers. These unique transport properties,
      together with density functional theory-based transport calculations, suggest a
      mechanism of resonant transport across the highly delocalized DPP backbones in
      the high bias regime. This study thus demonstrates the unique properties of
      diketopyrrolopyrrole derivatives in achieving highly efficient long-range charge
      transport in single-molecule devices.

PMID- 30280892
TI  - Metal-Doping of La5.4MoO11.1 Proton Conductors: Impact on the Structure and
      Electrical Properties.
AB  - La5.4MoO11.1 proton conductors with different metal doping (Ca2+, Sr2+, Ba2+,
      Ti4+, Zr4+, and Nb5+) have been prepared and structurally and electrically
      characterized. Different polymorphs are stabilized depending on the doping and
      cooling rate used during the synthesis process. The most interesting results are
      obtained for Nb-doping, La5.4Mo1- xNb xO11.1- x/2, where single compounds are
      obtained in the compositional range 0 <= x <= 0.2. These materials are fully
      characterized by structural techniques such as X-ray and neutron powder
      diffraction and transmission electron microscopy, which independently confirm the
      changes of polymorphism. Scanning electron microscopy and impedance spectroscopy
      measurements in dry/wet gases (N2, O2, and 5% H2-Ar) showed an enhancement of the
      sinterability and electrical properties of the materials after Nb-doping.
      Conductivity measurements under very reducing conditions revealed that these
      materials are mixed ionic-electronic conductors, making them potential candidates
      for hydrogen separation membranes.

PMID- 30280893
TI  - Ultrasensitive Characterization of Charge Heterogeneity of Therapeutic Monoclonal
      Antibodies Using Strong Cation Exchange Chromatography Coupled to Native Mass
      Spectrometry.
AB  - In therapeutic monoclonal antibody (mAb) development, charge heterogeneity of a
      mAb molecule is often associated with critical quality attributes and is
      therefore monitored throughout development and during QC release to ensure
      product and process consistency. Elucidating the cause of each charge variant
      species is an involved process that often requires offline fractionation by ion
      exchange chromatography (IEX) followed by mass spectrometry (MS) analysis,
      largely due to the incompatibility of conventional IEX buffers for direct MS
      detection. In this study, we have developed a method that combines a generic
      strong cation exchange (SCX) chromatography step with ultrasensitive online
      native MS analysis (SCX-MS) optimized for mAb separation and detection. As
      demonstrated by analyzing mAb molecules with a wide range of pI (isoelectric
      point) values, the developed method can consistently achieve both high-resolution
      IEX separation and ultrasensitive MS detection of low-abundance charge variant
      species. Using this method, we analyzed the charge heterogeneity of NISTmAb
      reference material 8671 (NISTmAb) at both whole antibody and subdomain levels. In
      particular, due to the high sensitivity, a nonconsensus Fab glycosylation site,
      present at a very low level (<0.1%), was directly detected in the NISTmAb sample
      without any enrichment. The structure and location of this Fab glycosylation was
      further characterized by peptide mapping analysis. Despite the extensive
      characterization of NISTmAb material in previous studies, this is the first time
      that this Fab-glycosylated variant has been identified in the NISTmAb,
      demonstrating the value of this new method in achieving a more comprehensive
      characterization of charge heterogeneity for therapeutic mAbs.

PMID- 30280895
TI  - Integrated and Quantitative Proteomic Approach for Charting Temporal and
      Endogenous Protein Complexes.
AB  - Proteins often assemble into multiprotein complexes for carrying out their
      biological functions. Affinity purification combined with mass spectrometry (AP
      MS) is a method of choice for unbiasedly charting protein complexes. Typically,
      genetically tagged bait protein and associated proteins are immunoprecipitated
      from cell lysate and subjected to in-gel or on-bead digestion for MS analysis.
      However, the sample preparation procedures are often time-consuming and skipping
      reduction and alkylation steps results in incomplete digestion. Here, by
      seamlessly combining AP with the simple and integrated spintip-based proteomics
      technology (SISPROT), we developed an integrated AP-MS workflow for
      simultaneously processing more than 10 AP samples from cells cultured in six-well
      plates in 2 h. Moreover, we developed a quantitation-based data analysis workflow
      for differentiating potential interacting proteins from nonspecific
      interferences. The AP-SISPROT ensures high digestion efficiency especially for
      large transmembrane proteins such as EGFR and high quantification precision for
      profiling temporal interaction network of key EGFR signaling protein GRB2 across
      four time points of EGF treatment. More importantly, the integration feature
      allows minimum sample lose and helps the development of an ideal AP-MS workflow
      for studying endogenous protein complexes by the CRISPR Cas9 technology for the
      first time. By generating endogenously expressed bait protein fused with affinity
      tag, protein complexes associated with endogenous Integrin-linked kinase (ILK)
      was identified with much higher selectivity as compared with overexpressed and
      tagged ILK. The AP-SISPROT technology and its combination with CRISPR Cas9
      technology should be generally applicable for studying protein complexes in a
      more efficient and physiologically relevant manner.

PMID- 30280896
TI  - Influences of Light Intensity and beta-Carotene on Polycyclic Aromatic
      Hydrocarbons and Aldehydes in Vegetable Oil: A Case Study Using Palm Oil.
AB  - This study investigated the effects of three light intensities on four types of
      palm oils during consecutive storage for 12 months at 4  degrees C. The
      concentrations of 4-hydroxy-2- trans-hexenal (4-HHE), 4-hydroxy-2- trans-nonenal
      (4-HNE), polycyclic aromatic hydrocarbon (PAH)4, and PAH8 in the oils
      significantly increased with the increasing light intensity after storage. The
      red palm oil had the lowest rate of increase of 4-HNE, while 5 degrees  palm oil
      had the highest rate of increase of the PAH, OPAH, 4-HNE, and peroxide values
      during storage. For the same type of oil, OPAHs increased significantly under a
      light intensity of 6000 lx (lx) after storage. The increasing concentrations of
      9FO, ATQ, and BaPO in the oils stored at 6000 lx showed a positive relation to
      their corresponding parent PAHs, indicating that PAH oxidation occurred at 6000
      lx. The results suggest that light intensity and beta-carotene may control PAHs,
      OPAHs, and 4-hydroxy-trans- alkenals for vegetable oil storage, transportation,
      and retail.

PMID- 30280894
TI  - Reversible and Site-Dependent Proton-Transfer in Zeolites Uncovered at the Single
      Molecule Level.
AB  - Zeolite activity and selectivity is often determined by the underlying proton and
      hydrogen-transfer reaction pathways. For the first time, we use single-molecule
      fluorescence microscopy to directly follow the real-time behavior of individual
      styrene-derived carbocationic species formed within zeolite ZSM-5. We find that
      intermittent fluorescence and remarkable photostability of carbocationic
      intermediates strongly depend on the local chemical environment imposed by
      zeolite framework and guest solvent molecules. The carbocationic stability can be
      additionally altered by changing para-substituent on the styrene moiety, as
      suggested by DFT calculations. Thermodynamically unstable carbocations are more
      likely to switch between fluorescent (carbocationic) and dark (neutral) states.
      However, the rate constants of this reversible change can significantly differ
      among individual carbocations, depending on their exact location in the zeolite
      framework. The lifetimes of fluorescent states and reversibility of the process
      can be additionally altered by changing the interaction between dimeric
      carbocations and solvated Bronsted acid sites in the MFI framework. Advanced
      multidimensional magic angle spinning solid-state NMR spectroscopy has been
      employed for the accurate structural elucidation of the reaction products during
      the zeolite-catalyzed dimerization of styrene in order to corroborate the single
      molecule fluorescence microscopy data. This complementary approach of single
      molecule fluorescence microscopy, NMR, and DFT collectively indicates that the
      relative stability of the carbocationic and the neutral states largely depends on
      the substituent and the local position of the Bronsted acid site within the
      zeolite framework. As a consequence, new insights into the host-guest chemistry
      between the zeolite and aromatics, in terms of their surface mobility and
      reactivity, have been obtained.

PMID- 30280897
TI  - Identification of beta-Sitosterol as in Vitro Anti-Inflammatory Constituent in
      Moringa oleifera.
AB  - beta-Sitosterol is a well known phytosterol in plants, but owing to its poor
      solubility in typical media, determining its cellular mechanisms has been proven
      to be difficult. In this study, we investigated the anti-inflammatory activity of
      beta-sitosterol (BSS) isolated from Moringa oleifera in two cell lines. Over a
      dose range of 7.5 to 30 MUM, BSS dispersed well in the medium as nanoparticles
      with diameters of 50 +/- 5 nm and suppressed the secretion of inflammatory
      factors from keratinocytes and macrophages induced by PGN, TNF-alpha, or LPS,
      such as TNF-alpha, IL-1beta, IL-6, IL-8, and ROS, separately. In addition, BSS
      significantly reduced the expression of NLRP3, a key component of NLRP3
      inflammasomes, and inhibited the activation of caspase-1. There was partial
      inhibition of NF-kappaB in macrophages. This is the first study to report an
      increase in the solubility of nearly water-insoluble phytosterols via the
      formation of nanoparticles and to delineate the formulation's capacity to inhibit
      the signal transduction pathways of inflammation in macrophages.

PMID- 30280898
TI  - Photocatalytic Activation of Less Reactive Bonds and Their Functionalization via
      Hydrogen-Evolution Cross-Couplings.
AB  - Cross-coupling reactions have been established as potential tools for manufacture
      of complex molecular frameworks of diversified interests by connecting two simple
      molecules through the formation of a carbon-carbon (C-C) or a carbon-heteroatom
      (C-X) bond. Conventional cross-couplings are transition metal-catalyzed reactions
      between electrophiles and nucleophiles. Generally, the electrophilic partner is
      an aryl or alkenyl halide, the nucleophile is an organometallic reagent, and both
      are obtained from prefunctionalization of their corresponding hydrocarbons.
      During the past decade, transition metal-catalyzed dehydrogenative cross
      couplings between two carbon-hydrogen (C-H) bonds and between one C-H bond and
      one heteroatom-hydrogen (X-H) bond, which build a C-C and a C-X linkage
      respectively, have emerged as an attractive strategy in synthetic chemistry. Such
      straightforward couplings allow use of less functionalized reagents, thus
      reducing the number of steps to the target molecule and minimizing waste
      production. However, such reactions involve the use of stoichiometric amounts of
      sacrificial oxidants such as peroxides, high-valent metals, and iodine(III)
      oxidants. This leads to low atom economy and possible generation of toxic wastes.
      Recently, visible light photocatalytic dehydrogenative cross-coupling reactions
      have received much attention due to their potential in utilizing sunlight as a
      source of energy making the process appealing. In this approach, metal complexes,
      organic dyes, or semiconductor quantum dots that absorb visible light are
      employed as photocatalysts. Upon irradiation, photocatalyst initiates single
      electron transfer with substrate(s) to generate a radical cation or radical anion
      of the substrate, which undergoes the desired reaction of interest. In this case,
      molecular oxygen is utilized as the oxidant with the formation of hydrogen
      peroxide as the only byproduct. These aspects make the process much greener than
      the corresponding transition metal-catalyzed dehydrogenative cross-coupling
      reactions. Research efforts from our group have led to the development of an
      environmentally benign strategy to construct a C-C bond from two different C-H
      bonds and to construct a C-X bond from one C-H bond and one X-H bond by visible
      light photocatalysis. Our approach, photocatalytic hydrogen-evolution cross
      coupling reactions, combines a photocatalyst with a proton reduction cocatalyst
      to create a dual catalyst system. The former catalyst uses light energy as the
      driving force for the cross-coupling, while the latter catalyst may capture
      electrons from the substrates or reaction intermediates to reduce the protons
      eliminated from the reactive scaffolds (C-H/C-H or C-H/X-H bonds) into molecular
      hydrogen (H2). Thus, without use of any sacrificial oxidant and under mild
      conditions, our dual catalyst system affords cross-coupling products with
      excellent yields with generation of an equimolar amount of H2 as the sole
      byproduct. The photocatalytic hydrogen-evolution cross-coupling is highly step
      and atom economical and particularly useful for reactions that involve species
      sensitive to oxidative conditions. This Account highlights the findings from our
      laboratories on photocatalytic hydrogen-evolution cross-coupling reactions
      featuring activation and functionalization of C(sp3)-H bonds adjacent to amino
      groups and to oxygen atoms in ethers, aromatic C(sp2)-H bonds, and several types
      of X-H bonds. We expect that this strategy for combining photocatalytic
      activation of C-H and X-H bonds with proton reduction holds significant potential
      for development of atom economical and environmentally benign transformations.

PMID- 30280899
TI  - Use of an Air-Stable Cu(I)-NHC Catalyst for the Synthesis of Peptidotriazoles.
AB  - We report the use of air-stable Cu(I)-NHC complex 4a as a catalyst for the
      efficient microwave-assisted synthesis of peptidotriazoles on solid phase.
      Compared with the usual conditions (CuI or CuSO4/NaAsc), catalyst 4a allowed the
      preparation of a series of peptidomimetic compounds containing a 1,2,3-triazole
      ring in their backbone without the oxidation of common side-chains. Overall, the
      peptidotriazoles were obtained in good yields (61-87%), in excellent purity
      (higher than 94%) and with low copper contamination.

PMID- 30280900
TI  - Delivery of Doxorubicin Using Double-Layered Core-Shell Nanocarrier Based on
      Magnetic Fe3O4 Core and Salep Shells.
AB  - Herein, we developed a magnetic drug delivery system based on magnetic Fe3O4
      nanoparticles with double shells of modified salep polysaccharide for the
      delivery of doxorubicin (Dox). The drug-loaded nanocarrier was synthesized in an
      easy way, and large amounts of drug molecules were loaded into the nanocarrier.
      The drug-loaded nanocarrier showed excellent pH responsibility in vitro, and
      large amounts of Dox were released at lower pH (60% release), whereas the
      nanocarrier was stable at neutral pH. The hemolysis assay results showed that the
      nanocarrier has negligible hemolytic effects on human red blood cells and showed
      good biocompatibility. Moreover, the result of coagulation assays showed that the
      nanocarrier was not active in any coagulation pathways. Cytotoxicity assays of
      nanocarrier and drug-loaded nanocarrier toward HeLa cells demonstrated that the
      nanocarrier has negligible toxicity, whereas the drug-loaded nanocarrier kills
      more than 90% of cells during 48 h. The flow cytometry analysis also showed that
      the uptake of drug-loaded nanocarrier into the cancerous cells is time-dependent
      and higher concentrations of drug internalized into the cells at longer
      incubation time. On the basis of the results, we suggest that the present
      nanocarrier can be applicable for in vivo drug delivery as an easy-made and cheap
      nanocarrier.

PMID- 30280901
TI  - Electrocatalytic Intermolecular C(sp3)-H/N-H Coupling of Methyl N-Heteroaromatics
      with Amines and Amino Acids: Access to Imidazo-Fused N-Heterocycles.
AB  - An efficient NH4I-mediated intermolecular annulation of methyl N-heteroaromatics
      with amines/amino acids was developed by virtue of anodic oxidation, providing a
      variety of functionalized imidazo-fused N-heterocycles with good to excellent
      yields. The practicality of this protocol was demonstrated by the readily
      available starting materials, broad substrate scope, water tolerance,
      scalability, and the diverse transformations of the electrolysis product.

PMID- 30280902
TI  - Diffusiophoresis of a Charged Porous Particle in a Charged Cavity.
AB  - The quasi-steady diffusiophoresis of a charged porous sphere situated at the
      center of a charged spherical cavity filled with a liquid solution of a symmetric
      electrolyte is analyzed. The porous particle can represent a solvent-permeable
      and ion-penetrable polyelectrolyte molecule or floc of nanoparticles in which
      fixed charges and frictional segments are uniformly distributed, whereas the
      spherical cavity can denote a charged pore involved in microfluidic or drug
      delivery systems. The linearized electrokinetic differential equations governing
      the ionic concentration, electric potential, and fluid velocity distributions in
      the system are solved by using a perturbation method with the fixed charge
      density of the particle and the zeta-potential of the cavity wall as the small
      perturbation parameters. An expression for the diffusiophoretic (electrophoretic
      and chemiphoretic) mobility of the confined particle with arbitrary values of a/
      b, kappa a, and lambda a is obtained in closed form, where a and b are the radii
      of the particle and cavity, respectively; kappa and lambda are the reciprocals of
      the Debye screening length and the length characterizing the extent of flow
      penetration into the porous particle, respectively. The presence of the charged
      cavity wall significantly affects the diffusiophoretic motion of the particle in
      typical cases. The diffusio-osmotic (electro-osmotic and chemiosmotic) flow
      occurring at the cavity wall can substantially alter the particle velocity and
      even reverse the direction of diffusiophoresis. In general, the particle velocity
      decreases with an increase in a/ b, increases with an increase in kappa a, and
      decreases with an increase in lambda a, but exceptions exist.

PMID- 30280903
TI  - Total Synthesis of the Proposed Structure of Mycobactin J.
AB  - The total synthesis of the proposed structure of mycobactin J (MJ), a metabolite
      of Mycobacterium tuberculosis, is presented. The highlights of the synthesis
      include a careful control of the Z-stereochemistry of the unsaturated long chain
      fatty acid, a biomimetic construction of the oxazoline building block and the
      carriage of an unprotected phenol throughout the synthesis.

PMID- 30280904
TI  - Trichophycins B-F, Chlorovinylidene-Containing Polyketides Isolated from a
      Cyanobacterial Bloom.
AB  - NMR-guided isolation (based on 1D 1H and 13C NMR resonances consistent with a
      chlorovinylidene moiety) resulted in the characterization of five new highly
      functionalized polyketides, trichophycins B-F (1-5), and one nonchlorinated
      metabolite tricholactone (6) from a collection of Trichodesmium bloom material
      from the Gulf of Mexico. The planar structures of 1-6 were determined using 1D
      and 2D NMR spectroscopy, mass spectrometry, and complementary spectroscopic
      procedures. Absolute configuration analysis of 1 and 2 were carried out by 1H NMR
      analysis of diastereomeric Mosher esters in addition to ECD spectroscopy, J-based
      configuration analysis, and DFT calculations. The absolute configurations of 3-6
      were proposed on the basis of comparative analysis of 13C NMR chemical shifts,
      relative configurations, and optical rotation values to compounds 1 and 2.
      Compounds 1-5 represent new additions to the trichophycin family and are
      hallmarked by a chlorovinylidene moiety. These new trichophycins and
      tricholactone (1-6) feature intriguing variations with respect to putative
      biosynthetic starting units, halogenation, and terminations, and trichophycin E
      (4) features a rare alkynyl bromide functionality. The phenyl-containing
      trichophycins showed low cytotoxicity to neuro-2A cells, while the alkyne
      containing trichophycins showed no toxicity.

PMID- 30280905
TI  - Alterations in serum zinc and polyunsaturated fatty acid concentrations in
      treatment naive HIV-diagnosed alcohol dependent subjects with liver injury.
AB  - Heavy alcohol drinking causes alterations in the metabolism of fatty acids and
      zinc that participate in inflammation and liver injury. Human Immunodeficiency
      Virus (HIV) infection has been reported to cause dysregulated polyunsaturated
      fatty acid (PUFAs) and zinc metabolism. In this pilot study, we examined the role
      of dysregulated PUFA metabolism and zinc deficiency in liver injury in the liver
      injury occurring in heavy drinkers with early stage HIV diagnosis. Fourteen heavy
      drinking alcohol dependent (AD) patients (seven with treatment naive HIV
      diagnosis [AD+HIV], and seven without HIV infection [AD]) participated in this
      study. Liver injury, serum zinc, PUFAs, viral load, CD4+ count, and drinking
      measures using Lifetime drinking history (LTDH), and Timeline Follow-back past 90
      days (TLFB90) assessments were evaluated. Liver injury was also assessed in seven
      age- and sex-matched socially drinking HIV treatment-naive patients who served as
      disease controls. Liver enzymes were significantly elevated in both AD+HIV and AD
      patients, and AD+HIV patients had significantly higher ALT levels than did AD
      patients, even with lower drinking. Serum zinc was significantly lower in AD+HIV
      patients. Only AD+HIV patients showed a significant elevation in linoleic acid
      (LA) and alpha-linoleic acid (ALA) levels. Serum zinc and ALT; LA and ALT; and
      ALA and ALT were significantly associated only in AD+HIV patients. The
      association between LA and ALT showed a higher effect than did the ALA?and ALT
      association in the AD+HIV patients. Interestingly, AD+HIV subjects (who drank
      less) nevertheless showed more liver injury compared to AD patients, who reported
      heavier drinking. HIV viral load by itself did not show any correlation with
      liver injury. We speculate that the the underlying proinflammatory response
      resulting from zinc deficiency and an elevation in serum LA likely contributed to
      liver injury in AD+HIV patients, even with a comparatively lower degree of heavy
      drinking.

PMID- 30280906
TI  - Association of Vitamin D Insufficiency and Protective Tenofovir Diphosphate
      Concentrations with Bone Toxicity in Adolescent Boys and Young Men Using
      Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Pre-Exposure Prophylaxis.
AB  - We examined associations of 25-hydroxy vitamin D (25-OHD), tenofovir disoproxil
      fumarate (TDF), and bone toxicity. We studied TDF/emtricitabine (FTC) HIV pre
      exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Bone
      toxicity was predefined using bone mineral density/content change from baseline
      to week 48. Baseline serum 25-OHD was dichotomized as <20 ng/mL
      (insufficient/deficient) versus >=20 (sufficient), and week 48 dried blood spot
      tenofovir diphosphate (TFV-DP) as >700 fmol/punch (protective against HIV
      acquisition) versus <=700. Associations were examined by univariate and
      multivariable logistic regression, reporting crude and adjusted odds ratios
      (ORs), with 95% confidence intervals (CIs). Of 101 enrolled, 69 had complete bone
      assessments and 25-OHD; of these, 59 had week 48 TFV-DP data. Median (Q1-Q3) age
      was 20 (18-21) years; 54% were black/African American. In univariate analysis,
      participants with baseline 25-OHD <20 ng/mL (OR = 5.4; 95% CI = 1.9-16.5) and
      blacks (OR = 4.9; 95% CI = 1.7-15.2) had greater odds of bone toxicity than those
      with 25-OHD >=20 or other races. TFV-DP was not associated with bone toxicity (OR
      = 1.6; 95% CI = 0.5-5.5). In multivariable analysis, compared with those with 25
      OHD >=20 and TFV-DP <=700, those with 25-OHD >=20 and TFV-DP >700 (OR = 11.5; 95%
      CI = 1.4-169.6), 25-OHD <20 and TFV-DP <=700 (OR = 19.4; 95% CI = 3.0-228.7), and
      25-OHD <20 and TFV-DP >700 (OR = 32.3; 95% CI = 3.3-653.6) had greater odds of
      bone toxicity after adjusting for race. In multivariable models, 25-OHD
      insufficiency, protective TFV-DP concentrations, and black race were
      significantly associated with bone toxicity after 48 weeks of TDF/FTC PrEP in
      YMSM. Clinical Trials Registration: NCT01769469.

PMID- 30280907
TI  - Demonstrating efficacy and effectiveness in clinical studies with recurrent event
      as primary end point: a chronic obstructive pulmonary disease example.
AB  - Pivotal clinical trials of persistent disorders such as chronic obstructive
      pulmonary disease and severe asthma often utilize recurrent event (e.g.,
      exacerbations) as primary study end point. Such infrequent and correlated end
      points usually have skewed distributions, which can result in clinical efficacy
      criterion being met even while clinical effectiveness may be poor. Patients,
      prescribers and, increasingly, payers want evidence of both a medicine's clinical
      efficacy and its effectiveness. This duality in evidentiary requirements is
      causing a shift from the traditional one-size-fits-all blockbuster drug
      development paradigm to newer patient-centric models. Using a simulated study, we
      illustrate how clinical studies using enrichment designs can collect and present
      such patient-centric evidence that will simultaneously demonstrate clinical
      efficacy and effectiveness, while increasing probability of trial success and
      overall efficiency.

PMID- 30280908
TI  - Percutaneous Nephrolithotomy with Different Temperature Irrigation and Effects on
      Surgical Complications and Anesthesiology Applications.
AB  - OBJECTIVE: Percutaneous nephrolithotomy (PCNL) is a widely accepted and
      frequently performed operation for large kidney stones. However, there is not
      much information about the effects of irrigation fluid temperature as well as
      many other factors that affect success and complications during the operation. In
      this study, we aimed to investigate the surgical and anesthesiological effects of
      irrigation fluid used in body temperature and room temperature during and after
      PCNL. MATERIAL AND METHODS: A total of 108 PCNL patients were performed between
      June 2016 and April 2018. The half of these patients (54) were performed with
      body temperature (37 degrees C) irrigation fluid, hence known as body temperature
      group (BTG), and the other half with room temperature (22 degrees C) irrigation
      fluid, called as room temperature group (RTG). For the study, we recorded the
      body temperature of the patients during and after the operation, the amount of
      irrigation fluid used, the size and location of the kidney stones, the duration
      of the operation, postoperative shivering time during the patient's wake-up
      period, pre- and postoperative hemoglobin value, additional blood requirements,
      postoperative analgesic requirements, and postoperative urinary tract infections.
      RESULTS: The age of patients, gender distribution, height, weight, body mass
      index, stone size, and postoperative analgesic requirement showed no significant
      differences in two groups. The postoperative body heat was significantly higher
      in the BTG than the RTG. The duration of waking was significantly higher in the
      RTG than the BTG. The amount of hemorrhage was significantly less in the patients
      who were irrigated in the RTG. CONCLUSION: The temperature of the irrigation
      fluid can affect many parameters in the PCNL. We recommend using irrigation in
      room temperature especially with patients having bleeding risks and irrigation
      fluid in body temperature especially with patients having anesthetic risks for
      easier waking process.

PMID- 30280909
TI  - Prospective Associations between Weekend Catch-Up Sleep, Physical Activity, and
      Childhood Obesity.
AB  - BACKGROUND: Catch-up sleep and low physical activity on weekends have been
      commonly documented. Preliminary evidence on Chinese children, however, has shown
      a variety of weekly physical activity patterns. This study examined the
      prospective associations between weekend catch-up patterns of sleep and physical
      activity and obesity over a 2-year period in Chinese children. METHODS:
      Prospective data from 599 children in the Understand Children's Activity and
      Nutrition (UCAN) cohort study were analyzed. Weekly patterns of obesogenic
      behaviors (physical activity and sleep duration) were assessed annually over a 2
      year period. Moderate-to-vigorous physical activity (MVPA) and sedentary time
      were determined by ActiGraph accelerometry. Data on sleep durations and
      sociodemographic factors were obtained from parental-reported questionnaires.
      Weekend catch-up sleep and MVPA patterns were calculated and examined in relation
      to childhood obesity after controlling for sociodemographic variables and
      sedentary time. RESULTS: Every additional hour of average weekly sleep duration
      was associated with a 16% decrease in the odds of obesity (OR: 0.841, 95%CI:
      0.709 - 0.999). After adjustment of average sleep duration, weekend sleep catch
      up categories showed no association with obesity risk. Over a 2-year period, half
      of the children demonstrated weekend catch-up MVPA. Weekend catch-up MVPA for
      less than 20 minutes (OR: 0.473, 95%CI: 0.258 - 0.867) or more than 20 minutes
      (OR: 0.505, 95%CI: 0.257 - 0.993) were both related to lower risk of obesity.
      CONCLUSIONS: Weekend catch-up sleep did not ameliorate the risk of childhood
      obesity, whereas weekend catch-up MVPA did reduce that risk. More research is
      needed to explore the factors contributing to these obesogenic behavior patterns.

PMID- 30280910
TI  - What gives them the right? Legal privilege and waivers of consent for research.
AB  - Waivers of informed consent for research participation are permitted in the
      United States under the Common Rule, the Health Insurance Portability and
      Accountability Act regulations, and the US Food and Drug Administration's
      Exception from Informed Consent rule for emergency research. We assess the novel
      question regarding what legal right researchers have to carry out research
      procedures on or about another person, be it experimental medical intervention,
      psychological or social manipulation, or invasion of privacy, without the
      permission of their subjects. Our analysis frames waivers of consent as a species
      of presumed consent, and we address the underlying empirical question of whether
      it is reasonable to believe that subjects from whom no consent is sought would in
      fact agree, if asked. A scoping review of what is known about participation and
      refusal rates in United States-based research suggests that a large minority, on
      average, do not agree to take part in research. Refusal rates vary widely. This
      suggests that, while researchers may assert the social utility of their studies
      are high enough to justify waivers, there is reason to suspect that many who
      would be enrolled under a waiver of consent would not want to be enrolled. We
      conclude that waivers should be rare and that institutional review boards and
      researchers must explicitly address study acceptability in the community at large
      and the target population of their proposed research.

PMID- 30280911
TI  - ENDOSCOPIC INTRAVESICAL FIBRIN GLUE APPLICATION IN THE TREATMENT OF REFRACTORY
      HEMORRHAGIC RADIATION CYSTITIS: A SINGLE COHORT PILOT STUDY.
AB  - Objective To evaluate the clinical value of endoscopic fibrin glue (FG)
      application therapy in treating hemorrhagic radiation cystitis (HRC). Patients
      and Methods This is a single cohort, prospective pilot study. We collected data
      from patients with HRC who were treated at our urology unit during the period May
      2014 to December 2016. Patients with grade >=2 HRC for whom conventional therapy
      and trans-urethral endoscopic electrocoagulation had failed were treated with
      endoscopic intravesical FG. The mean follow-up was 26.2 +/- 9.78 months. Our
      analysis included data on patient demographics, pelvic malignancies, radiotherapy
      regimens, total dose of radiation received, time of onset and severity of
      hematuria, and previous intravesical management. Following the FG intervention,
      patients' clinical status was defined as either: (1) clinical response, absence
      of dysuria, urgency, and frequency; discontinuation of analgesic medication; and
      Foley catheter removal, but with ongoing hematuria grade <2; (2) complete
      response, clinical response and no further hematuria; or (3) no response, no
      clinical response and sustained hematuria. Results A total of 20 patients (12
      women and 8 men, with a mean age of 69 +/- 7.5 years) were treated with 12 mL of
      FG intravesically, using endoscopic application. Of the 20 patients, 16 (80%) had
      a complete response and 4 (20%) had a clinical response. In the case of four
      patients (20%), treatment was carried out twice. Mean hospital stay was 6 +/- 2.5
      days. The intervention showed good tolerability in all patients. No major adverse
      events were reported. Bladder spasms were the only minor adverse events reported
      in 6 patients (30%). Conclusion Application of FG is an effective, practical,
      affordable and repeatable procedure for the treatment of grade >=2 HRC.

PMID- 30280912
TI  - Food Service Workers: Reliable Assessors of Food Intake in Hospitalized Patients.
AB  - Early detection of malnutrition in hospitalized patients is of paramount
      importance. As poor food intake is a marker of malnutrition risk, a simple and
      accurate method to monitor intake is valuable. This quality assurance project
      aimed to determine if food service workers (FSW) were able to provide accurate
      estimates of patient intakes through visually assessing meal trays at an acute
      care hospital. FSW conducted visual estimates of patient trays after meals using
      the meal plate pictorial rating scale adapted from the My Meal Intake Tool and
      translated their estimates into one of 5 consumption levels (0%, 25%, 50%, 75%,
      or 100%). A total of 401 patient meal estimates were validated using the food
      weighing method. Spearman's correlations between percent calories consumed
      (determined by weight) and estimates by FSW were 0.624 (n = 137, P < 0.001),
      0.771 (n = 134, P < 0.001), and 0.829 (n = 130, P < 0.001), for breakfast, lunch,
      and supper, respectively. Paired Wilcoxon tests and the Kruskal-Wallis H test
      showed that accuracy varied for breakfast, lunch, and supper. The overall
      sensitivity and specificity of FSW for detecting patient intake <=50% was 81% and
      88%, respectively. These findings identify that FSW can accurately estimate
      patient intake, contributing an important marker for the detection of
      malnutrition.

PMID- 30280913
TI  - Determining Student Food Insecurity at Memorial University of Newfoundland.
AB  - PURPOSE: Our study compared the prevalence of food insecurity among 3 student
      groups attending Memorial University of Newfoundland (MUN): International (INT),
      Canadian out-of-province (OOP), and Newfoundland and Labrador (NL). Factors
      associated with food insecurity were also investigated. METHODS: Data were
      collected via an online survey distributed to an estimated 10 400 returning MUN
      students registered at a campus in St. John's, NL. Respondents were recruited
      through e-mails, posters, and social media. Ten questions from the Canadian
      Household Food Security Survey Module adult scale were asked to assess food
      security. Logistic regression was used to compare rates of food insecurity
      between the three population subgroups. RESULTS: Of the 971 eligible student
      respondents, 39.9% were food insecure (moderate or severe). After controlling for
      program type, parental status, living arrangement, and primary income source, OOP
      and INT students were 1.63 (95% CI = 1.11-2.40) and 3.04 (95% CI = 1.89-4.88)
      times more likely, respectively, to be food insecure than NL students.
      CONCLUSIONS: Approximately 40% of participating MUN students experienced food
      insecurity, a higher proportion than reported for the overall provincial
      population. Groups at high risk of food insecurity include INT students, students
      with children, and those relying on government funding as their primary income.

PMID- 30280914
TI  - Parental views of antenatal testing and termination following a diagnosis of
      cleft lip.
AB  - Fetal anomaly screening at 18-21 weeks now routinely includes cleft lip. If
      detected, the manner in which the diagnosis is communicated can considerably
      influence prospective parents' decision-making in regard to further testing and
      termination of pregnancy (TOP). Given the known psychological impact of an
      antenatal diagnosis of cleft lip on prospective parents, this study aimed to
      explore the decision-making process from the parents' perspective, in order to
      evaluate how well current practice is meeting guidelines. Data from 217 parents
      of children born with cleft lip (with or without cleft palate) were collected
      using a mixed-methods online survey. Respondents reported feeling upset, offended
      and/or anxious following the diagnosis, due to unsatisfactory information and a
      perceived lack of empathy from health professionals. Some respondents had felt
      under pressure to make a decision quickly, with a minority having regretted
      undergoing amniocentesis, and/or experiencing significant distress at having come
      close to TOP unnecessarily. A number of suggestions are made as to how the
      discussion between parents and health professionals could be improved, to ensure
      that the information and support needs of families affected by cleft lip are
      fully addressed.

PMID- 30280915
TI  - Three Distraction Methods for Pain Reduction During Cystoscopy: A Randomized
      Controlled Trial Evaluating the Effects on Pain, Anxiety, and Satisfaction.
AB  - BACKGROUND: Cystoscopy is a safe diagnostic procedure commonly used to evaluate
      lower urinary tract symptoms. This can cause pain, anxiety, and dissatisfaction
      in patients undergoing cystoscopy. OBJECTIVES: The aim of this study was to
      compare the effects on pain, anxiety, and satisfaction of distraction methods
      used during cystoscopy. DESIGN: Single-center, open-label, randomized, parallel
      group trial. SETTING: Cystoscopy unit of a training and research hospital in
      Turkey. PARTICIPANTS: Male patients >=18 years of age who underwent rigid
      cystoscopy for the first time. METHODS: A total of 120 male patients were
      recruited and randomized into four groups as music, stress ball, video, and
      control group. Data were collected using visual analog scale for pain and
      satisfaction, State-Trait Anxiety Inventory for anxiety, and hemodynamic
      parameters. The primary outcome was the difference with respect to pain scores
      among intervention groups. Other outcome measures were anxiety and satisfaction
      scores. RESULTS: Pain severity during cystoscopy was found to be significantly
      lower in the intervention groups than the control group. In the video group, the
      severity of pain during cystoscopy was also found to be significantly lower than
      music and stress ball groups (p = 0.006, p < 0.001). After cystoscopy, anxiety
      levels were significantly lower and satisfaction levels were significantly higher
      in the intervention groups than in the control group. Anxiety levels were
      significantly lower in the video group than music and stress ball groups (p <
      0.001, p < 0.001). Satisfaction levels were also significantly higher after
      cystoscopy in the video group than in the music and stress ball groups (p =
      0.018, p = 0.018). CONCLUSIONS: According to this study, distraction methods used
      during rigid cystoscopy were found to have a reducing effect on pain, anxiety,
      and dissatisfaction. As the results of the study are evaluated, video should be
      recommended to be the first preferred distraction method during rigid cystoscopy.

PMID- 30280916
TI  - Nosocomial Pneumonia Elicits an Endothelial Proteinopathy: Evidence for a Source
      of Neurotoxic Amyloids in Critically Ill Patients.

PMID- 30280917
TI  - Exploring Social Justice Advocacy in Dietetic Education: A Content Analysis.
AB  - PURPOSE: To explore the extent to which knowledge- and skill-based learning
      regarding social justice and/or social justice advocacy is included in the course
      descriptions of required courses of accredited, English-speaking dietitian
      training programs in Canada. METHODS: This study is a mixed-methods content
      analysis of required course descriptions sampled from university academic
      calendars for accredited, English-speaking dietitian training programs across
      Canada. RESULTS: Quantitative analysis showed that required course descriptions
      (n = 403) included few instances of social justice-related terminology (n = 63).
      Two themes emerged from the qualitative analysis: competing conceptualizations of
      social issues and dietitians' roles; prioritization of science-based knowledge
      and ways of knowing. CONCLUSIONS: Accredited, English-speaking dietitian training
      programs in Canada appear to include little knowledge- or skill-based learning
      regarding social justice issues and advocacy. Supporting future dietitians to
      pursue leadership roles in redressing social injustices and socially just
      dietetic practice may require more explicit education and training about social
      justice issues and advocacy skills.

PMID- 30280918
TI  - Grocery Shopping, Dinner Preparation, and Dietary Habits among Adolescents and
      Young Adults in Canada.
AB  - PURPOSE: The current study aimed to characterize grocery shopping and dinner
      preparation behaviours among young people in Canada and to examine associations
      with eating habits. METHODS: A cross-sectional online survey was conducted with
      2008 participants aged 16-24 from across Canada. The survey measured self
      reported grocery shopping and dinner preparation behaviours, frequency of eating
      breakfast and eating meals prepared away from home, frequency of vegetable and
      fruit intake, and socio-demographic characteristics. Chi-square tests examined
      differences in proportions; logistic and linear regressions examined dietary
      habits, including covariates for grocery shopping and dinner preparation and
      socio-demographics. RESULTS: Overall, 37.3% had helped with grocery shopping in
      the past week, and 84.3% had participated in dinner preparation at least 1 day in
      the past week. Engaging in shopping at least once weekly was associated with
      increased vegetable and fruit consumption only, whereas more frequent engagement
      in dinner preparation was associated with increased vegetable and fruit
      consumption, more frequent breakfast consumption, and fewer meals consumed that
      were prepared away from home (P < 0.001 for all). CONCLUSIONS: Increased
      participation in grocery shopping and dinner preparation were associated with
      healthier dietary habits. Interventions that increase these behaviours may
      contribute to improving dietary behaviours among adolescents and young adults.

PMID- 30280919
TI  - Response to Barry re: Learning Curves and Timing of Surgical Trials: Robotic
      Kidney Transplantation with Regional Hypothermia.

PMID- 30280920
TI  - Describing Food Availability in Schools Using Different Healthy Eating
      Guidelines: Moving Forward with Simpler Nutrition Recommendations.
AB  - PURPOSE: Internationally, there is debate on whether a nutrient or a food-based
      approach to policy is more effective. This study describes the food/beverage
      availability in schools in Nova Scotia through a comparison of a traditional
      nutrient classification ("Maximum/Moderate/Minimum"), currently used in the
      provincial school policy and a simplified food-based system ("Core/Extra").
      METHODS: School food environment audits were conducted in schools (n = 25) to
      record the food and beverages available. Registered dietitians categorized
      information using both the nutrient-based and simplified food-based
      classification systems. Number and percent in each category were described for
      items. RESULTS: Food and beverage items consisted of breakfast, lunch, snacks,
      beverages, and vending of which 81% were permissible by the policy, whereas only
      54% were categorized as Core. Many snacks and vending items classified as Extra
      fell within either Moderate (45% and 35%, respectively) or Minimum (29% and 33%,
      respectively) categories. CONCLUSIONS: Dietitians have a role to support
      interpretation of classification systems for school nutrition policies. The
      nutrient-based classification used in the policy permitted some items not
      essential to a healthy diet as defined by the Extra food-based classification.
      However, the food-based Core/Extra categorization had less detail to classify
      nutrients.

PMID- 30280921
TI  - Effect of Testosterone Use on Bone Mineral Density in HIV-Infected Men.
AB  - HIV-infected men have increased rates of osteoporosis and fracture compared to
      HIV-uninfected men. Testosterone use among HIV-infected men is common. In HIV
      uninfected men, testosterone increases bone mineral density (BMD), but its
      effects have not been evaluated in HIV-infected men. In a substudy of Multicenter
      AIDS Cohort Study (MACS), the Bone Strength Substudy (BOSS) enrolled 202 HIV
      infected and 201 HIV-uninfected men aged between 50 and 69 years. Study
      participants underwent dual-energy X-ray absorptiometry (DXA) at the lumbar spine
      (LS), total hip (TH), and femoral neck (FN) and detailed assessment of
      osteoporosis risk factors. We used multivariable linear regression to determine
      associations and 95% confidence intervals (CIs) between self-reported
      testosterone use and T-scores at the LS, TH, and FN after adjustment for
      demographics, behavioral covariates, comorbidities, and other traditional
      osteoporosis risk factors. HIV-infected men reported more frequent testosterone
      use (22% vs. 4%; p < .001) and had lower median BMD T-score at TH than HIV
      uninfected men (0.0 vs. 0.3; p = .045) but similar T-scores at LS and FN. In the
      overall study population, testosterone use was associated with significantly
      greater BMD T-score at LS (0.68; 95% CI: 0.22-1.13). In HIV-infected men with
      virologic suppression, testosterone was significantly associated with higher BMD
      T-score at LS (0.95; 95% CI: 0.36-1.54) and TH (0.45; 95% CI: 0.04-0.86). Current
      testosterone use is common in HIV-infected men and was associated with higher
      BMD, compared to those not taking testosterone. Testosterone's role in reducing
      fracture risk in HIV-infected men should be investigated.

PMID- 30280922
TI  - Survey of Nutrition Practice in Patients with Severe Sepsis among Canadian
      Registered Dietitians.
AB  - PURPOSE: The purpose of this study was to determine the opinions and reported
      nutrition practices of Canadian Registered Dietitians (RDs) with regard to
      feeding patients with severe sepsis. METHODS: In 2017, surveys were sent to 112
      eligible Canadian RDs in 10 provinces who were practicing in an intensive care
      environment. The survey included embedded branching logic questions developed to
      address major facets of sepsis, critical illness, and nutrition. The survey
      instrument assimilated all data in an anonymous manner, so respondents could not
      be linked to their answers. RESULTS: Of the 64 RDs who responded (57% response
      rate), the majority practiced in adult intensive care (81%), within an academic
      center (59%), and in a mixed unit (73%). A wide variability of Canadian RDs'
      opinions and practice was reported in determining energy requirements, enteral
      nutrition (EN) practice, EN with vasoactive agents, parenteral nutrition (PN),
      and supplemental micronutrients. CONCLUSIONS: Practice variability of Canadian
      RDs likely reflects gaps in both evidence and guidelines for severe sepsis.
      Further research efforts are needed to customize nutritional requirements in the
      patient with evolving sepsis, EN with patients at high risk for gastrointestinal
      dysfunction, optimizing PN, and the role of micronutrients.

PMID- 30280923
TI  - 'It's different for girls': Gender differences in the friendships and conflict of
      autistic and neurotypical adolescents.
AB  - This mixed-methods study examined gender differences in the friendships and
      conflict experiences of autistic girls and boys relative to their neurotypical
      peers. In total, 102 adolescents (27 autistic girls, 26 autistic boys, 26
      neurotypical girls, and 23 neurotypical boys), aged between 11 and 18 years
      completed the Friendship Qualities Scale, the Revised Peer Experiences
      Questionnaire and were interviewed about their friendships. Results demonstrated
      that in many ways, the friendships and social experiences of autistic girls are
      similar to those of neurotypical girls. Autistic girls, however, have
      significantly more social challenges than their neurotypical peers, experiencing
      more conflict and finding that conflict harder to manage successfully. Autistic
      boys showed quantitatively different friendship patterns to all other groups.
      There were consistent gender differences in the type of conflict which boys and
      girls experienced, regardless of diagnostic status. These findings suggest that
      gender, rather than diagnosis per se, plays a critical role in the way that
      autistic adolescents perceive and experience their social relationships.

PMID- 30280924
TI  - The rationale for combination therapy in patients with aggressive B-cell non
      Hodgkin lymphoma: ten questions.
AB  - Rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone
      immunochemotherapy remains standard of care for first-line treatment of diffuse
      large B-cell lymphoma (DLBCL). High-dose chemotherapy and stem cell
      transplantation is offered to most relapsing/refractory patients who respond to
      salvage therapy. This Q&A review evaluates recommended management strategies for
      second and subsequent lines of therapy in patients with DLBCL, outlining the
      relative efficacies of currently available options including novel agents such as
      ibrutinib and CAR-T cells. The combination of pixantrone and rituximab is
      currently under investigation as a second-line treatment for patients ineligible
      for stem cell transplantation, while pixantrone monotherapy is the only
      therapeutic option approved for multiply relapsed and refractory DLBCL beyond the
      second line at this time.

PMID- 30280925
TI  - Dietary Changes Albertan Women Make During Pregnancy: Thematic Analysis of Self
      reported Changes and Reasons.
AB  - PURPOSE: To explore dietary changes Albertan women make during pregnancy, reasons
      they make changes, and alignment with prenatal nutrition recommendations.
      METHODS: Women up to 6 months postpartum were recruited in public health centres
      and Primary Care Networks. Qualitative data were collected through a self
      administered survey including 2 open-ended questions that asked about changes
      made to food/beverage intake during pregnancy and why these changes were made.
      RESULTS: A majority (n = 577) of the 737 women completing the survey described
      changes they made to their food/beverage intake during pregnancy and 193
      respondents provided reasons for these changes. Increased intake of
      fruits/vegetables, meat, milk, and their alternatives (n = 600); limiting or
      avoidance of foods/beverages known to be harmful during pregnancy (n = 445); and
      increased food/fluid intake or meal/snack frequency (n = 405) were commonly
      reported dietary changes. Motivations relating to health and to control
      physiological changes/manage health conditions were the most frequent reasons
      provided. CONCLUSIONS: Women make diverse dietary changes and have various
      motivations for food choices during pregnancy. A majority make dietary changes to
      support a healthy pregnancy. However, the motivation to control discomforts and
      respond to hunger and thirst sensations reflect a stronger influencer on women's
      choices than is currently addressed in prenatal nutrition messages.

PMID- 30280926
TI  - Dynamics of testosterone levels in patients with newly detected glucose
      abnormalities and acute myocardial infarction.
AB  - OBJECTIVE:: Low testosterone has been associated with increased cardiovascular
      risk and glucose abnormalities. This study explored the prevalence of low
      testosterone, dynamics over time and prognostic implications in acute myocardial
      infarction patients with or without glucose abnormalities. METHODS:: Male acute
      myocardial infarction patients (n = 123) and healthy controls (n = 124) were
      categorised as having normal or abnormal glucose tolerance (impaired glucose
      tolerance or diabetes) by oral glucose tolerance testing. Testosterone was
      measured at hospital admission, discharge, 3 and 12 months thereafter in
      patients. Patients and controls were followed for 11 years for major
      cardiovascular events (cardiovascular death/acute myocardial
      infarction/stroke/severe heart failure). RESULTS:: At hospital admission, more
      patients had low testosterone (?300 ng/dl) and lower median levels than controls
      (64 vs 28%; p < 0.001 and 243 vs 380 ng/dl; p < 0.01). At the subsequent time
      points, testosterone had increased to 311, 345 and 357 ng/dl. Patients with
      abnormal glucose tolerance had the highest prevalence (75%) of low levels. In
      adjusted Cox regression models, neither total nor free testosterone predicted
      major cardiovascular events. CONCLUSION:: Low testosterone levels were common in
      male acute myocardial infarction patients in the acute phase, especially in the
      presence of abnormal glucose tolerance, but increased over time indicating that
      testosterone measured in close proximity to acute myocardial infarction should be
      interpreted with caution.

PMID- 30280927
TI  - Maternal Prepregnancy Overweight and Obesity Are Associated with Reduced Physical
      Fitness But Do Not Affect Physical Activity in Childhood: The Amsterdam Born
      Children and Their Development Study.
AB  - BACKGROUND: Maternal overweight/obesity during pregnancy increases offspring's
      risks of obesity and cardiovascular disease (CVD). A possible pathway is by
      reduced physical fitness and physical activity (PA) levels in children of
      overweight/obese mother. We assessed whether maternal prepregnancy
      overweight/obesity independently determines cardiorespiratory fitness (CRF),
      muscular strength, moderate-to-vigorous physical activity (MVPA), and sedentary
      behavior (SB) in 8- to 9-year-old children. We also assessed whether child's fat
      mass (FM) mediates these associations. METHODS: One hundred ninety-four children
      of Dutch ethnicity aged 8.6 (+/- 0.4) years were randomly selected from a
      prospective birth cohort, the Amsterdam Born Children and their Development
      (ABCD) study. CRF was assessed by the 20-m multistage shuttle run test (20-m
      MSRT), muscular strength by hand dynamometry, and MVPA and SB by accelerometry.
      The association of prepregnancy body mass index (BMI) >= 25 kg/m2 with these
      outcome measures was assessed by multivariable linear regressions. RESULTS: Mean
      (+/- standard deviation) attained 20-m MSRT stage was 5.3 (+/- 1.7). Compared
      with children from normal weight women, children of women with prepregnancy
      overweight/obesity attained a 0.80 (95% confidence interval: 0.15-1.50) lower
      stage, adjusted for child's sex and MVPA. This association was not mediated by
      birthweight or child's FM at age 5 years. Maternal prepregnancy
      overweight/obesity was not associated with child's muscular strength, MVPA, or
      SB. CONCLUSIONS: Maternal prepregnancy overweight/obesity was associated with
      reduced childhood CRF, but not with muscular strength, PA, or SB. Birthweight and
      FM at age 5 years did not mediate this association. Reduced CRF may partly
      explain the increased CVD risk in children of overweight/obese women.

PMID- 30280928
TI  - Cephalometric comparison of adult anterior open bite treatment using clear
      aligners and fixed appliances.
AB  - OBJECTIVES:: To compare fixed appliances and clear aligner therapy in correcting
      anterior open bite and in controlling the vertical dimension in adult patients
      with hyperdivergent skeletal patterns. MATERIALS AND METHODS:: In this
      retrospective study, two treatment groups of adult (>=18 years old)
      hyperdivergent patients (mandibular plane angles of >=38 degrees ) with anterior
      open bites were included: 17 fixed appliance patients and 36 clear aligner
      patients. Thirteen cephalometric measurements representing the vertical dimension
      were reported for each group. A two-sample t-test was used to assess differences
      in changes in mandibular plane angle and overbite between the two treatment
      groups. RESULTS:: There were no statistical differences found in the magnitude of
      overbite correction and the changes in any of the cephalometric measurements for
      vertical control. The clear aligner group showed a slightly greater amount of
      lower incisor extrusion ( P = .009). The main mechanism of open bite correction
      was similar between the two treatment groups and was accomplished through
      retroclination of the upper and lower incisors while maintaining the vertical
      position of the upper and lower molars. CONCLUSIONS:: Cephalometric comparison of
      anterior open bite correction and changes in the mandibular plane angle
      associated with use of clear aligners and fixed appliances did not demonstrate
      statistically significant differences in adult hyperdivergent patients.

PMID- 30280931
TI  - In Vitro and In Vivo Performance of Tissue-Engineered Tendons for Anterior
      Cruciate Ligament Reconstruction: Response.

PMID- 30280929
TI  - Topology of the Structural Social Brain Network in Typical Adults.
AB  - Although a large body of research has identified discrete neuroanatomical regions
      involved in social cognition and behavior (the "social brain"), the existing
      findings are based largely on studies of specific brain structures defined within
      the context of particular tasks or for specific types of social behavior. The
      objective of the current work was to view these regions as nodes of a larger
      collective network and to quantitatively characterize both the topology of that
      network and the relative criticality of its many nodes. Large-scale data mining
      was performed to generate seed regions of the social brain. High-quality
      diffusion MRI data of typical adults were used to map anatomical networks of the
      social brain. Network topology and nodal centrality were analyzed using graph
      theory. The structural social brain network demonstrates a high degree of global
      functional integration with strong local segregation. Bilateral dorsomedial
      prefrontal cortices and amygdala play the most central roles in the network.
      Strong probabilistic evidence supports modular divisions of the social brain into
      subnetworks bearing good resemblance to functionally classified clusters. The
      present network-driven approach quantifies the structural topology of the social
      brain as a whole. This work can serve as a critical benchmark against which to
      compare (1) developmental change in social brain topology over time (from infancy
      through adolescence and beyond) and (2) atypical network topologies that may be a
      sign or symptom of disorder (as in conditions such as autism, Williams syndrome,
      schizophrenia, and others).

PMID- 30280933
TI  - Recurvatum.

PMID- 30280932
TI  - In Vitro and In Vivo Performance of Tissue-Engineered Tendons for Anterior
      Cruciate Ligament Reconstruction: Letter to the Editor.

PMID- 30280934
TI  - Procedural Shortcomings With Near Point of Convergence Assessment May Lead to
      Inappropriate Prognosis of Concussion Injury in Athletes: Letter to the Editor.

PMID- 30280935
TI  - Procedural Shortcomings With Near Point of Convergence Assessment May Lead to
      Inappropriate Prognosis of Concussion Injury in Athletes: Response.

PMID- 30280936
TI  - Purification and Characterization of Pasteuricin Produced by Staphylococcus
      pasteuri RSP-1 and Active against Multidrug-Resistant Staphylococcus aureus.
AB  - Staphylococcus aureus is an important pathogen implicated in various diseases,
      including staphylococcal food poisoning. Bacteriocins are considered safe and
      effective antimicrobial substances for the prevention of the growth of pathogenic
      bacteria. In this article, we describe the purification and characterization of
      pasteuricin, a novel bacteriocin produced by Staphylococcus pasteuri RSP-1. A
      cell-free supernatant of S. pasteuri RSP-1 exerted strong antimicrobial activity
      against staphylococci, including methicillin-resistant S. aureus (MRSA), and gram
      positive bacteria. The loss of antimicrobial activity upon treatment with
      proteolytic enzymes confirmed the proteinaceous nature of pasteuricin. A rapid
      and pronounced bactericidal effect of pasteuricin was confirmed by a live-dead
      bacterial viability assay. To our knowledge, pasteuricin is the first reported S.
      pasteuri bacteriocin that inhibits S. aureus. Because pasteuricin is
      characterized by strong antimicrobial activity and high stability, it has
      potential as an alternative antimicrobial agent to antibiotics.

PMID- 30280937
TI  - Cryopreservation of Human Adipose-Derived Stem Cells for Use in ex vivo Regional
      Gene Therapy for Bone Repair.
AB  - The development of an ex vivo regional gene therapy clinical pathway using
      adipose-derived stem cells (ASCs) may require cryopreservation for cell culture,
      storage, and transport prior to clinical use. ASCs isolated from five donors were
      transduced with a lentiviral vector containing BMP-2. Three groups were assessed:
      transduction without cell freezing (group 1), freezing of cells for 3 weeks
      followed by transduction (group 2), and cell transduction prior to freezing
      (group 3). Nontransduced cells were used as a control. The cluster of
      differentiation (CD) marker profiles, cell number, BMP-2 production, and
      osteogenic potential were measured. The CD marker profile (CD44, CD73, CD90, and
      CD105) was unchanged after cryopreservation. Cell number was equivalent among
      cryopreservation protocols in transduced and nontransduced cells. There was a
      trend toward decreased BMP-2 production in group 3 compared to groups 1 and 2.
      Osteogenic potential based on Alizarin red concentration was higher in group 2
      compared to group 3, with no difference compared to group 1. Freezing ASCs prior
      to transduction with a lentiviral vector containing BMP-2 has no detrimental
      effect on cell number, BMP-2 production, osteogenic potential, or
      immunophenotype. Transduction prior to freezing, however, may limit the BMP-2
      production and potential osteogenic differentiation of the ASCs.

PMID- 30280938
TI  - Hair follicle miRNAs: a novel biomarker for primary blast Induced-Mild traumatic
      brain injury.
AB  - CONTEXT: Due to the wide use of improvised explosive devices during modern
      warfare, primary blast-derived mild traumatic brain injury (mTBI) has become a
      major medical condition in the military. With minimal visually identifiable
      symptoms, an effective molecular biomarker system is desirable. OBJECTIVE: We
      assessed the potential of mammalian hair follicle miRNAs as an mTBI biomarker.
      MATERIALS AND METHODS: Due to their well-established roles in mTBI molecular
      pathology, the expression level of miR-183, miR-26a, miR-181c, miR-29a, miR-34a
      and miR-27b was determined using qRT-PCR in whisker hair follicles from rats
      subject to head-only exposure to a single-pulse shock wave. Based on established
      transcriptomics profiles, sub-network enrichment analysis (SNEA) was also
      conducted. RESULTS: The results revealed that molecular networks involving miR
      183, miR-26a and miR-181c were enriched in multiple treatments, whereas sub
      networks of miR-29a, miR-34a and miR-27b were unique to individual exposure
      groups. DISCUSSION: Our study showed that all six miRNAs were reflective of the
      mTBI signature involved in cellular responses. Noteworthy was that the decrease
      in the transcript levels of miR-181c was correlated with shockwave exposure
      severity. CONCLUSION: This study demonstrates for the first time that mammalian
      hair follicles are capable of housing miRNA biomarkers for TBI.

PMID- 30280939
TI  - Synthetic Toll-like receptor agonists for the development of powerful malaria
      vaccines: a patent review.
AB  - INTRODUCTION: Currently, there is no efficient vaccine available against clinical
      malaria. However, continuous efforts have been committed to develop powerful
      antimalarial vaccine by discovery of novel antigens with in-depth understanding
      of its nature, immunogenicity, and presentation (delivery adjuvants). Moreover,
      another important part of vaccine development includes discovery of better
      immunostimulatory formulation components (immunostimulants). A protective vaccine
      against malaria requires antigen-specific B and T helper cell responses as well
      as cytotoxic T lymphocyte (CTL) responses. A long-lasting B and T memory cell
      production is also required for effective malaria vaccine. Since activation of
      Toll-like receptors (TLRs) promotes both innate inflammatory responses as well as
      the induction of adaptive immunity, several initiatives have been mounted during
      the last few years for the use of TLR agonists as malaria vaccine adjuvants.
      Areas covered: The review summarizes reports related to the use and development
      of TLR agonists as malaria vaccine adjuvants and describes various strategies
      involved for the selection of specific antigens and TLR agonists. Expert opinion:
      TLR agonists are promising adjuvants for the development of effective malaria
      vaccine, allowing for both innate inflammatory responses as well as the induction
      of adaptive immunity.

PMID- 30280940
TI  - Pembrolizumab for the treatment of gastric cancer.
AB  - INTRODUCTION: Gastric cancer is one of a few gastrointestinal malignancies in
      which immunotherapy has shown meaningful activity. Pembrolizumab is the first and
      only immune checkpoint inhibitor to be FDA-approved in gastric cancer. Areas
      Covered: This review summarizes the current and emerging clinical evidence for
      immune checkpoint inhibitors in advanced and metastatic gastric cancer, with a
      focus on pembrolizumab. Expert Commentary: Pembrolizumab has shown impressive
      activity in the third-line treatment of locally advanced and metastatic gastric
      cancer. It is currently being studied as upfront therapy in combination with
      chemotherapy. The emerging understanding of the molecular alterations and tumor
      immune microenvironment as predictors of immunotherapy response in gastric cancer
      are discussed. The impact of gastric mucosal dysbiosis on gastric carcinogenesis
      and the modulation of immunotherapy response by the gut microbiome are also
      reviewed.

PMID- 30280941
TI  - The effect of polymer molecular weight and cell seeding density on viability of
      cells entrapped within PEGDA hydrogel microspheres.
AB  - Cell microencapsulation can be used in tissue engineering as a scaffold or
      physical barrier that provides immunoisolation for donor cells. When used as a
      barrier, microencapsulation shields donor cells from the host immune system when
      implanted for cell therapies. Maximizing therapeutic product delivery per volume
      of microencapsulated cells necessitates first optimising the viability of
      entrapped cells. Although cell microencapsulation within alginate is well
      described, best practices for cell microencapsulation within polyethylene glycol
      is still being elucidated. In this study we microencapsulate mouse preosteoblast
      cells within polyethylene glycol diacrylate (PEGDA) hydrogel microspheres of
      varying molecular weight or seeding densities to assess cell viability in
      relation to cell density and polymer molecular weight. Diffusion studies revealed
      molecule size permissible by each molecular weight PEGDA towards correlating
      viability with polymer mesh size. Results demonstrated higher cell viability in
      higher molecular weight PEGDA microspheres and when cells were seeded at higher
      cell densities.

PMID- 30280942
TI  - Using Photovoice as a participatory method to identify and strategize community
      participation with people with intellectual and developmental disabilities.
AB  - BACKGROUND: Adults with intellectual and developmental disabilities (I/DD)
      experience barriers to community participation, yet their insider experiences of
      environmental barriers and supports to participation are largely absent from the
      literature. AIM/OBJECTIVE: The aims of this research were to evaluate Photovoice
      as a participatory research method, examine environmental barriers and supports
      to community participation, and develop strategies to support self-determination
      and community participation for and with people with I/DD. MATERIAL AND METHOD:
      This study utilized a participatory action research (PAR) approach in which
      participants used Photovoice during interviews and audits of participation
      environments to identify high interest participation activities and document
      supports and barriers in these environments. Data analysis utilized an iterative,
      participatory approach in which researchers and participants teamed up to select,
      contextualize, and codify the data. Thematic analyses involved both inductive and
      realist approaches. RESULTS/FINDINGS: Participants included 146 community
      dwelling adults with I/DD from three U.S. urban sites. We present a conceptual
      model of nine themes at microsystem, mesosystem, exosystem, macrosystem, and
      chronosystem environmental levels. CONCLUSIONS: Using Photovoice as a
      participatory method to strategize community participation can help ground
      systems change efforts in the voices of people with I/DD. SIGNIFICANCE: By
      including people with I/DD in conversations that concern them, researchers and
      practitioners can support this population in ways that they find meaningful.

PMID- 30280943
TI  - PEG-PCL modification and intestinal sustained-release of solid lipid
      nanoparticles for improving oral bioavailability of 2-methoxyestradiol.
AB  - The primary purpose of the present study was to design and optimize a solid lipid
      nanoparticle (SLN) formulation of the poorly water-soluble drug 2
      methoxyestradiol (2-ME) to improve its oral bioavailability and prolong the
      duration of therapeutic drug level. SLN was modified by amphipathic PEG-PCL (PLN)
      and then encapsulated in pH-sensitive microparticles (MP) by spray drying
      technology. Several properties of 2-ME PLN-MP were characterized including
      particle size, drug loading and drug or PLN release. After oral administration of
      2-ME PLN-MP, retention time in mice were evaluated by in vivo imaging technology
      and the pharmacokinetic parameters in rats were determined by HPLC. The results
      demonstrated that PEG-PCL modification of 2-ME SLN significantly decreased
      particle size and delayed drug release without influencing IC50 in 4T1 cells. 2
      ME PLN in the microparticles showed significant pH-sensitive release in the
      simulated gastrointestinal fluid and controlled release in the intestine. The PLN
      (labeled with IR-780 iodide) prolonged significantly fluorescence duration time
      compared to the SLN and the prolongation was further enhanced by the PLN-MP
      formulation. Furthermore, as compared to the suspension, the PLN-MP formulation
      showed a 56.66-fold delay in Tmax, a 10.36-fold extension in MRT and a 140.86
      fold increase in the relative bioavailability in rat. The research work in the
      paper suggests that the PLN-MP could serve as a practical oral preparation for 2
      ME in future cancer therapy.

PMID- 30280944
TI  - A structural perspective on the PP-loop ATP pyrophosphatase family.
AB  - Derived from an ancient ATP-hydrolyzing Rossmann-like fold protein, members of
      the PP-loop ATP pyrophosphatase family feature an absolutely conserved P-loop
      like "SxGxDS/T" motif used for binding and presenting ATP for substrate
      adenylylation (AMPylation). Since the first family member was reported more than
      20 years ago, numerous representatives catalyzing very diverse reactions have
      been characterized both functionally and structurally. The availability of more
      than 100 high quality structures in the protein data bank provides an excellent
      opportunity to gain structural insights into the generally conserved catalytic
      mechanism and the uniqueness of the reactions catalyzed by family members. In
      this work, we conducted a thorough database search for the PP-loop ATP
      pyrophosphatase family members, resulting in the most comprehensive and up-to
      date collection that includes 18 enzyme families. Structure comparison of
      representative family members allowed us to identify common structure features in
      the core catalytic domain, as well as four highly variable regions that define
      the unique chemistry for each enzyme family. The newly identified enzymes,
      particularly those from pathogens, warrant further research to enlarge the scope
      of this ever-expanding and highly diverse enzyme superfamily for use in potential
      bioengineering and biomedical applications.

PMID- 30280945
TI  - Letter to the Editor: "Impact of Age on Disease Progression and Microenvironment
      in Oral Cancer".

PMID- 30280946
TI  - Vaginal bleeding/spotting with conjugated estrogens/bazedoxifene, conjugated
      estrogens/medroxyprogesterone acetate, and placebo.
AB  - OBJECTIVE: In the 1-year phase 3 Selective estrogens, Menopause, And Response to
      Therapy-5 trial, cumulative amenorrhea rates with conjugated
      estrogens/bazedoxifene (CE/BZA) were similar to placebo and higher than with
      conjugated estrogens/medroxyprogesterone acetate (CE/MPA). This post hoc analysis
      reports bleeding/spotting rates in 4-week intervals (cycles) and 3-month
      intervals (quarters) with these therapies and the percentage of cases
      attributable to spotting only. METHODS: Generally healthy postmenopausal women
      with menopausal symptoms recorded vaginal bleeding/spotting in daily diaries
      while receiving CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, CE 0.45 mg/MPA 1.5
      mg, or placebo. RESULTS: A total of 1596 women in the modified intent-to-treat
      population contributed data. Incidence of bleeding/spotting was significantly (p
      < 0.001) lower with CE 0.45 mg/BZA 20 mg (0.54-4.44%), CE 0.625 mg/BZA 20 mg
      (1.26-5.02%), and placebo (1.55-4.82%) compared with CE 0.45 mg/MPA 1.5 mg (8.81
      25.63%) in all 4-week cycles. Each quarter, <10% of women taking CE/BZA doses or
      placebo had bleeding/spotting, significantly (p < 0.001) less than the 21-36%
      with CE 0.45 mg/MPA 1.5 mg. Odds ratio for bleeding/spotting with CE 0.45 mg/BZA
      20 mg vs CE 0.45 mg/MPA 1.5 mg was 0.1 in each quarter (95% CI, Q1-Q3: 0.1-0.2;
      Q4: 0.1-0.3). Across all treatments, most (88-100%) bleeding/spotting cases were
      spotting only. Mean days of bleeding/spotting were <1 per quarter with CE/BZA
      doses and placebo, which was significantly (p < 0.01) less than the 3-5 days per
      quarter with CE/MPA. CONCLUSIONS: Bleeding/spotting with CE/BZA treatment was
      similar to placebo and significantly less frequent than with CE/MPA treatment.
      Most cases were spotting only across all treatments.

PMID- 30280947
TI  - Site specific hypermethylation of CpGs in Connexin genes 30, 26 and 43 in
      different grades of glioma and attenuated levels of their mRNAs.
AB  - AIM: Gliomas, the intracranial tumours are considered the deadliest malignancies.
      The gap junctional Connexins (Cxs) that maintain cellular homeostasis perform a
      unique function in glial tumour suppression. However, the differential
      methylation patterns of Cxs were not revealed in glioma so far. The current study
      attempts to categorise promoter methylation of Cx30 and Cx26 and intron
      methylation of Cx43 in different grades of human glioma. MATERIALS AND METHODS:
      About 85 glioma patients with pathologically confirmed grades and 15 control
      brain tissues were recruited in the study. Bisulphite-PCR-Single Stranded
      Conformation analysis(SSCA), Bisulphite sequencing and MeDIP-qPCR were carried
      out to assess methylation status and Cx mRNA levels were also analysed to
      evaluate the effect of methylation. RESULTS: We found that promoter CpG
      islands(CpGs) reside in Sp1 and Ap2 sites of Cx30 and 26 were hypermethylated in
      high grades (HG) of glioma rather than low grades. The input % of both was
      significantly increased (p < 0.03) in progressive grades. Interestingly, Cx43
      could exhibit a significant increase (p < 0.05) in input % only in grade IV.
      While, Cx30 and 26 mRNAs were downregulated according to their methylation status
      in progressive fashion with grades, Cx43 was downregulated irrespective of intron
      methylation. CONCLUSION: Thus, we suggest that the sites and extent of
      methylation of Cxs (30 and 26 but not in 43) are found to be altered. In
      different grades of glioma can provide better appreciation of the grade of the
      patient and might help in strategies based on epigenetic approaches.

PMID- 30280948
TI  - Health Benefits In 2018: Modest Growth In Premiums, Higher Worker Contributions
      At Firms With More Low-Wage Workers.
AB  - The annual Henry J. Kaiser Family Foundation Employer Health Benefits Survey
      found that in 2018 the average annual premium for single coverage rose 3 percent
      to $6,896 and the average annual premium for family coverage rose 5 percent to
      $19,616. Covered workers contributed 18 percent of the cost for single coverage
      and 29 percent of the cost for family coverage, on average, with considerable
      variation across firms. Eighty-five percent of covered workers face a general
      annual deductible before they use most services, including the 29 percent of
      covered workers who are enrolled in a high-deductible health plan with a savings
      option. The share of firms covering services provided via telemedicine has
      increased steadily over the past several years. Nearly a quarter of large
      employers expect the elimination of the individual mandate to result in lower
      take-up in plan offerings.

PMID- 30280949
TI  - Response to Letter to the Editor: "Impact of Age on Disease Progression and
      Microenvironment in Oral Cancer".

PMID- 30280950
TI  - Neonatal epidermolysis bullosa: Lessons to learn about genetic counselling.
AB  - Epidermolysis Bullosa (EB) is a heterogeneous group of congenital blistering
      diseases that usually presents in the neonatal period. EB is classified into
      three major categories, each with many subtypes based on the precise location at
      which separation or blistering occurs, namely epidermolysis bullosa simplex
      (EBS), junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis
      bullosa (DEB). We describe genetics of neonatal EB in Hong Kong. Two neonates of
      consanguineous Pakistani parents had the EB-Pyloric Atresia (EB-PA) variant. One
      had a 4 kb homozygous deletion of exon 19-25 of the ITGB4 gene, and the other
      with only a histopathological diagnosis. Both died of sepsis in infancy. Aberrant
      COL7A1 mutations in the dominant and recessive EB were described. Genetic
      analysis, together with histopathological classification is important to aid
      prognosis and counselling. JEB and EB-PA are associated with consanguinity and
      mortality during infancy. Morbidity and prognosis of the autosomal dominant DEB
      is optimistic. The autosomal recessive DEB is more severe, with neonatal onset
      and recurrent blistering. It is also associated with chronicity and malignant
      changes when the child reaches adulthood. Exact genetic diagnosis aids in
      counselling of the family concerning the prognosis in the affected child and the
      risk of affected children in future pregnancies.

PMID- 30280951
TI  - Community-based participatory research to promote healthy lifestyles among Latino
      immigrant families with youth with disabilities.
AB  - BACKGROUND/AIMS: Community-based participatory research (CBPR) is an optimal
      approach that brings together community stakeholders, researchers and
      practitioners in an effort to understand and address social issues and health
      disparities experienced by vulnerable populations. Latino immigrant families in
      the United States with youth and young families with disabilities have
      experienced a number of barriers in gaining positive health outcomes. These
      families face challenges in maintaining a healthy lifestyle, placing them at high
      risk for obesity, diabetes, and other chronic health conditions. The purpose of
      this study was to develop a healthy lifestyles intervention in collaboration with
      Latino immigrant families with youth and young adults with disabilities using a
      CBPR approach, and to examine the impact of the intervention from participants'
      perspectives. METHODS: Grounded in the principles of CBPR, we developed a
      partnership with community stakeholders to create a healthy lifestyles
      intervention aimed at meeting the needs of Latino families in the United States.
      During and following implementation of the intervention, we conducted focus
      groups with 12 intervention participants to examine the impact of the
      intervention. RESULTS: Participants identified the intervention program as
      meeting a need in the community and reported specific positive aspects related to
      health behaviors, social learning, inclusion, community participation, and peer
      advocacy. DISCUSSION: CBPR healthy lifestyle interventions are relevant to the
      needs of Latino immigrant families with youth and young adults with disabilities.
      Health professionals should involve community residents in the design of healthy
      lifestyles programming to ensure strategies for change are relevant and
      relatable.

PMID- 30280952
TI  - Understanding health disparities for individuals with intellectual disability
      using photovoice.
AB  - BACKGROUND: Individuals with intellectual disability (ID) are at an increased
      risk for health disparities that serve as barriers to participation in daily
      occupations. Understanding the lived experience of individuals with ID can
      illuminate barriers and facilitators to these health-promoting occupations.
      Commonly used methods examining health for individuals with ID may not reveal
      important information about their daily participation potentially due to
      cognitive or communication limitations. Participatory action research including
      Photovoice is a viable alternative to meet their unique needs. OBJECTIVE: The
      purpose of this study was to describe the process of using a Photovoice method
      with individuals with ID and present results from two participants to understand
      their meaning of health. METHOD: An analysis of two participants is provided to
      illustrate the use of Photovoice. RESULTS: Three themes, Personal Identity of
      Health, Nutrition, and Meaningful Occupation were identified using photos,
      personal narratives, and focus group data. CONCLUSIONS: Participants had complex
      definitions of health that are better understood through the composite of
      narrative descriptions and visual data as compared to more commonly used research
      methods. The use of a Photovoice method allowed participants to communicate
      additional depth and complexity of their understanding of health that has not
      been previously captured.

PMID- 30280953
TI  - Major effects on blood-retina barrier passage by minor alterations in design of
      polybutylcyanoacrylate nanoparticles.
AB  - Because the blood-brain barrier (BBB) is an obstacle for drug-delivery, carrier
      systems such as polybutylcyanoacrylate (PBCA) nanoparticles (NPs) have been
      studied. Yet, little is known of how physiochemical features such as size,
      surfactants and surface charge influence BBB passage in vivo. We now used a rat
      model of in vivo imaging of the retina - which is brain tissue and can reflect
      the situation at the BBB - to study how size and surface charge determine NPs'
      ability to cross the blood-retina barrier (BRB). Interestingly, for poloxamer 188
      modified, DEAE-dextran-stabilised, fluorescent PBCA NPs, decreasing the average
      zeta-size from 272 nm to 172 nm by centrifugation reduced the BRB passage of the
      NPs substantially. Varying the zeta potential within the narrow range of 0-15 mV
      by adding different amounts of stabiliser revealed that 0 mV and 15 mV were less
      desirable than 5 mV which facilitated the BRB passage. Moreover, whether the
      fluorescent marker was adsorbed or incorporated also influenced the transport
      into the retina tissue. Thus, minor changes in design of nano-carriers can alter
      physicochemical parameters such as size or zeta potential, thus substantially
      influencing NPs' biological distribution in vivo, possibly by interactions with
      blood constituents and peripheral organs.

PMID- 30280954
TI  - Toxicology and Pharmacology of an AAV Vector Expressing Codon-optimized RPGR in
      RPGR-deficient Rd9 Mice.
AB  - AGTC is developing a recombinant adeno-associated virus (rAAV) vector AGTC-501,
      also designated AAV2tYF-GRK1-RPGRco, to treat retinitis pigmentosa (RP) in
      patients with mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene.
      The vector contains a codon-optimized human RPGR cDNA (RPGRco) driven by a
      photoreceptor-specific promoter (G protein-coupled receptor kinase 1, GRK1) and
      is packaged in an AAV2 capsid with three surface tyrosine residues changed to
      phenylalanine (AAV2tYF). We conducted a safety and potency study of this vector
      administered by subretinal injection in the naturally occurring RPGR-deficient
      Rd9 mouse model. Sixty Rd9 mice (20 per group) received subretinal injection in
      the right eye of vehicle (control) or AAV2tYF-GRK1-RPGRco at one of two dose
      levels (4 * 108 or 4 * 109 vg/eye) and were followed for 12 weeks after
      injection. Vector injections were well tolerated with no systemic toxicity. There
      was a trend towards reduced ERG b-wave amplitudes in the high vector dose group
      that was not statistically significant. There were no clinically important
      changes in hematology or clinical chemistry parameters and no vector-related
      ocular changes in-life or by histological examination. Dose-dependent
      immunolabeling of RPGR protein expression, mainly in the inner segment of
      photoreceptors and the adjacent connecting cilium region, was observed in all
      vector-treated eyes examined. Sequence integrity of the codon-optimized RPGR was
      confirmed by sequencing of PCR-amplified DNA, or cDNA reverse transcribed from
      total RNA, extracted from vector-treated retinal tissues, and by sequencing of
      RPGR protein obtained from transfected HEK 293 cells. These results support the
      use of rAAV2tYF-GRK1-RPGRco in clinical studies in patients with XLRP caused by
      RPGR mutations.

PMID- 30280955
TI  - Transcriptional quiescence in primordial germ cells.
AB  - In most animal species, newly formed primordial germ cells (PGCs) acquire the
      special characteristics that distinguish them from the surrounding somatic cells.
      Proper fate specification of the PGCs is coupled with transcriptional quiescence,
      whether they are segregated by determinative or inductive mechanisms.
      Inappropriate differentiation of PGCs into somatic cells is thought to be
      prevented due to repression of RNA polymerase (Pol) II-dependent transcription.
      In the case of a determinative mode of PGC formation (Drosophila, Caenorhabditis
      elegans, etc.), there is a broad downregulation of Pol II activity. By contrast,
      PGCs display only gene-specific repression in organisms that rely on inductive
      signaling-based mechanism (e.g., mice). In addition to the global block of Pol II
      activity in PGCs, gene expression can be suppressed in other ways, such as
      chromatin remodeling and Piwi-mediated RNAi. Here, we discuss the mechanisms
      responsible for the transcriptionally silent state of PGCs in common experimental
      animals, such as Drosophila, C. elegans, Danio rerio, Xenopus, and mouse. While a
      PGC-specific downregulation of transcription is a common feature among these
      organisms, the diverse nature of underlying mechanisms suggests that this
      functional trait likely evolved independently on several instances. We discuss
      the possible biological relevance of these silencing mechanisms vis-a-vis fate
      determination of PGCs.

PMID- 30280956
TI  - CIZ1-F, an alternatively spliced variant of the DNA replication protein CIZ1 with
      distinct expression and localisation, is overrepresented in early stage common
      solid tumours.
AB  - CIZ1 promotes cyclin-dependent DNA replication and resides in sub-nuclear foci
      that are part of the protein nuclear matrix (NM), and in RNA assemblies that are
      enriched at the inactive X chromosome (Xi) in female cells. It is subjected to
      alternative splicing, with specific variants implicated in adult and pediatric
      cancers. CIZ1-F is characterized by a frame shift that results from splicing
      exons 8-12 leading to inclusion of a short alternative reading frame (ARF),
      excluding the previously characterized C-terminal NM anchor domain. Here, we
      apply a set of novel variant-selective molecular tools targeted to the ARF to
      profile the expression of CIZ1-F at both transcript and protein levels, with
      focus on its relationship with the RNA-dependent and -independent fractions of
      the NM. Unlike full-length CIZ1, CIZ1-F does not accumulate at Xi, though like
      full-length CIZ1 it does resist extraction with DNase. Notably, CIZ1-F is
      sensitive to RNase identifying it as part of the RNA-fraction of the NM. In
      quiescent cells CIZ1-F transcript expression is suppressed and CIZ1-F protein is
      excluded from the nucleus, with re-expression not observed until the second cell
      cycle after exit from quiescence. Importantly, CIZ1-F is over-expressed in common
      solid tumors including colon and breast, pronounced in early stage but not highly
      proliferative late stage tumors. Moreover, expression was significantly higher in
      hormone receptor negative breast tumors than receptor positive tumors. Together
      these data show that CIZ1-F is expressed in proliferating cells in an unusual
      cell cycle-dependent manner, and suggest that it may have potential as a tumor
      biomarker.

PMID- 30280957
TI  - Evaluating cellular uptake of gold nanoparticles in HL-7702 and HepG2 cells for
      plasmonic photothermal therapy.
AB  - AIM: A novel methodology is provided to quantitatively measure the gold (Au) mass
      internalized in a cell for effective implementation of plasmonic photothermal
      therapy (PPTT). MATERIALS & METHODS: The cellular uptake of 4-mercaptobenzoic
      acid-labeled Au nanoparticles (NPs) is investigated via Raman mapping and
      inductively coupled plasma-mass spectrometry and the efficiency of in vitro PPTT
      is evaluated. RESULTS & CONCLUSION: The cellular uptake is strongly affected by
      the size of the Au NPs, concentration of the Au NPs, incubation time and cell
      type. By optimizing the experimental parameters, the results show that a
      significant damage is caused to the HepG2 cells and slight harm is caused to the
      HL-7702 cells during PPTT. This demonstrates a high potential for developing
      effective photothermal therapy for tumor tissues.

PMID- 30280958
TI  - Experiences and perceptions of social constraints and social change among
      lesbian, gay, bisexual and transgender persons in Lesotho.
AB  - Lesbian, gay, bisexual, transgender and other sexually and gender diverse persons
      negotiate for their identities, create communities and advocate for their rights
      throughout the world. However, there are limited data about the perceptions of
      social change among sexually and gender diverse persons in contexts where same
      sex sexual practices have been recently decriminalised, such as in 2010 in
      Lesotho. We conducted semi-structured in-depth interviews with sexually and
      gender diverse persons (n = 46) and six key informants. Findings were analysed
      using Social Worlds Theory. Participants discussed social constraints and
      marginalisation across structural (legal systems, employment, education),
      community (beliefs that sexual and gender diversity are incongruent with Basotho
      culture; stigma), and familial (tensions with religion and cultural gendered
      economic traditions) dimensions. The narratives also revealed perceived change
      across structural (changing norms in legal, employment and education spheres),
      community (larger community and LGBT community change), familial (negotiating
      acceptance), and internal (active resistance) domains. The findings reported here
      can inform multi-faceted programmes to challenge stigma, violence and gender
      inequity; build social capital; and address the health and human rights
      priorities of sexually and gender diverse persons in Lesotho.

PMID- 30280959
TI  - 'Age of despair', or 'when life starts': migrant and refugee women negotiate
      constructions of menopause.
AB  - There has been a call for research on migrant and refugee women's negotiation of
      diverse discourses and cultural constraints associated with sexual embodiment,
      including menopause, in order to facilitate sexual and reproductive health and
      understand gendered subjectivity. This study examined the construction and
      experience of menopause among migrant and refugee women who had settled in
      Australia or Canada in the last 10 years. Eighty-four individual interviews and
      16 focus groups comprising 85 participants were conducted (total n = 169), with
      women aged 18 years and over from Afghanistan, India (Punjab), Iraq, Somalia,
      South Sudan, Sri-Lanka (Tamil), Sudan and various South American (Latina)
      backgrounds. Thematic decomposition identified three discursive themes: Menopause
      as the Age of Despair; a Discourse of Silence and Secrecy; and Menopause as a
      Life Stage - or when Life Starts. Negative constructions of menopause, associated
      with silence and secrecy, were evident across different cultural groups, with
      implications for women's positioning and experience of menopausal change and
      embodiment. However, resistance to negative discourse was also evident. This was
      primarily associated with having received menopause education and more open
      communication about menopausal change, suggesting that education and health
      information can facilitate affirming aspects of menopause.

PMID- 30280960
TI  - Primary Lymphedema of the Upper Extremities: Clinical and Lymphoscintigraphic
      Features in 23 Patients.
AB  - BACKGROUND: Primary idiopathic lymphedema is an uncommon condition that typically
      affects the lower extremities. Patients have a malformed lymphatic system that
      causes subcutaneous fluid and adipose deposition. Rarely, the disease also has
      been described in the upper extremities. The purpose of this study was to
      investigate a cohort of patients with primary arm lymphedema to better understand
      the disease. METHODS: Patients evaluated in our Lymphedema Program between 2008
      and 2018 were reviewed for individuals with upper extremity primary lymphedema.
      Gender, age of onset, morbidity, associated features, and management were
      identified. Transit of radiolabeled tracer and dermal backflow on
      lymphoscintigraphy were recorded. RESULTS: Twenty-three patients of 234
      individuals with primary lymphedema had upper extremity disease (9.8%). Eleven
      subjects were male. Age of onset was infancy (n = 15), adolescence (n = 5), or
      adulthood (n = 3). The disease affected the left arm (n = 11), right arm (n = 9),
      or both upper extremities (n = 3). Lymphoscintigraphy in 15 patients exhibited
      delayed transit of tracer and 2 illustrated dermal backflow. One-half of
      individuals also had primary lower extremity lymphedema (six unilateral and six
      bilateral). None of the patients in the cohort exhibited a family history of
      lymphedema. Two individuals had Turner syndrome. Morbidity included infection (n
      = 5), other lymphatic anomalies (n = 6), and lymphangiosarcoma (n = 1).
      CONCLUSIONS: The upper extremities are a rare location for primary lymphedema and
      patients often also have lymphedema of the legs. Compared with that of the lower
      extremities, primary disease of the arm is more likely to be associated with
      systemic lymphatic dysfunction and has a lower risk of familial transmission.

PMID- 30280961
TI  - Anti-Aging Passion and Pragmatism: Effective Bedfellows at Last.

PMID- 30280962
TI  - Biomechanical Effect Of Masticatory Forces In Tenting Screws Used For Vertical
      Ridge Augmentation : A 3D Finite Element Analysis.
AB  - The purpose of this study was to analyze stresses induced in tenting screws by
      occlusal forces in a vertically augmented ridge, using a three-dimensional finite
      element analysis (FEA).The study was performed by means of FEA with the use of
      tenting screws that stabilize non resorbable membrane in a vertically augmented
      ridge. A customized three-dimensional analysis was performed by computer
      simulation to determine the pattern of stress distribution in tenting screws and
      the surrounding bone when applying axial and off-axial forces. The magnitude of
      the stresses in the model were calculated during these simulations. Based on
      these findings, different stress patterns on tenting screws with axial and off
      axial forces did not cause mechanical instability. This study revealed that when
      applying vertical force, the maximum stress in the surrounding bone was found at
      the most coronal portion of it. The highest and lowest magnitude of stress can be
      seen at the top and end of screws, respectively. When oblique force was applied,
      the highest stress values are observed at the coronal and middle portion of the
      bone and screws, respectively. Overall, all of the tenting screws tested were
      sufficiently stable to maintain membrane volume against vertical and oblique
      forces.

PMID- 30280963
TI  - Transplanted Human Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Support
      Liver Regeneration in Gunn Rats.
AB  - Gunn rats bear a mutation within the uridine diphosphate glucuronosyltransferase
      1a1 (Ugt1a1) gene resulting in high serum bilirubin levels as seen in Crigler
      Najjar syndrome. In this study, the Gunn rat was used as an animal model for
      heritable liver dysfunction. Induced mesenchymal stem cells (iMSCs) derived from
      embryonic stem cells (H1) and induced pluripotent stem cells were transplanted
      into Gunn rats after partial hepatectomy. The iMSCs engrafted and survived in the
      liver for up to 2 months. The transplanted iMSCs differentiated into functional
      hepatocytes as evidenced by partially suppressed hyperbilirubinemia and
      expression of multiple human-specific hepatocyte markers such as albumin,
      hepatocyte nuclear factor 4alpha, UGT1A1, cytokeratin 18, bile salt export pump,
      multidrug resistance protein 2, Na/taurocholate-cotransporting polypeptide, and
      alpha-fetoprotein. These findings imply that transplanted human iMSCs can
      contribute to liver regeneration in vivo and thus represent a promising tool for
      the treatment of inherited liver diseases.

PMID- 30280964
TI  - In situ synthesis of bacterial cellulose/copper nanoparticles composite membranes
      with long-term antibacterial property.
AB  - Bacterial cellulose (BC), with unique structure and properties, has attracted
      much attention in the biomedical field, especially in using as wound dressing.
      However, pure BC lacks the antimicrobial activity, which limits its application
      in wound healing. To solve this problem, copper nanoparticles (Cu NPs) loaded BC
      membranes were fabricated by using in situ chemical reduction method. The
      morphology and chemical composition of the composite membranes were characterized
      by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier Transform
      Infrared (FTIR) and thermogravimetric analysis (TGA). The results showed that Cu
      NPs evenly distributed and anchored in the three-dimensional (3-D) nanofiber
      network of BC through physical bonding. Traces of Cu2O were observed on the
      membranes probably because the Cu2+ was incompletely reduced. The Cu NPs loaded
      BC membranes showed efficient long-term antibacterial activity against
      Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) even after
      immersion in deionized water for up to 90 days. The composite membranes kept
      sustained release of copper ion, which may contribute to the long-term
      antibacterial activity. Furthermore, with controlled Cu concentration, BC/Cu
      membranes did not show obvious cytotoxicity to normal human dermal fibroblasts
      (NHDF). In all, the present results reveal that BC/Cu membranes with efficient
      antibacterial activity are promising to be used as wound dressings.

PMID- 30280965
TI  - Mnemonic emotion regulation: a three-process model.
AB  - Emotion regulation comprises attempts to influence when and how emotions are
      experienced and expressed. It has mostly been conceived of as proactive (e.g.
      situation selection) or reactive (e.g. attentional distraction), but it may also
      be retroactive and involve memory. I term such past-oriented activity mnemonic
      emotion regulation and propose that it involves increasing or decreasing access
      to or altering the characteristics of a memory. People may increase access to a
      memory and make it more likely that it will be retrieved in the future, for
      example by rehearsing a pleasant memory. They may decrease access to a memory and
      make it less likely that intrusions will be experienced in the future, for
      example by repeatedly trying to stop an unpleasant memory from being retrieved.
      Finally, people may alter the characteristics of a memory and change its content
      or context, for example by replacing a negative impression with a productive
      interpretation. I discuss how mnemonic emotion regulation may be instigated (e.g.
      via elaborate rehearsal) as well as the different motives (e.g. hedonic motives)
      people may have for engaging in regulation. Also, I discuss possible benefits of,
      variations in, and improvements of mnemonic emotion regulation.

PMID- 30280966
TI  - Buccal fat pad-derived stem cells in three-dimensional rehabilitation of large
      alveolar defects: A report of two cases.
AB  - This case report sought to describe efficient clinical applications of adipose-
      derived stem cells (AdSCs) originated from buccal fat pad (BFP) in combination
      with conventional guided bone regeneration as protected healing space for
      reconstruction of large alveolar defects after multi-impacted teeth extractions.
      The first case was a 19-year-old female with several impacted teeth in the
      maxillary and mandibular regions, which were not capable to forced erupt and
      recommended by the orthodontist for surgical extraction. Following this
      procedure, a large bone defect created and this space was filled by AdSCs loaded
      natural bovine bone mineral (NBBM) which protected with lateral ramus cortical
      plates, micro-screws and collagen membrane. After 6 months post- guided bone
      regeneration, she was subjected to six and seven implants placements,
      respectively in the maxilla and mandible. At 10 months postoperatively,
      radiographic evaluations revealed thorough survival of implants. The second case
      was a 22-year-old male with the same complain and large bony defects created
      after his teeth extraction. After 6 months post- guided bone regeneration, he
      received four dental implants in his maxilla and seven implants in the mandible.
      At 48 months postoperatively, radiographies showed complete survival of implants.
      As the result, this approach represented a considerable amount of three
      dimensional bone formation in both cases which enable us to utilize dental
      implant therapy for rehabilitation of the whole dentition. The application of
      AdSCs isolated from BFP in combination with NBBM can be considered as an
      efficient treatment for bone regeneration in large alveolar bone defects.

PMID- 30280967
TI  - Marginal role of von Willebrand factor-binding protein and coagulase in the
      initiation of endocarditis in rats with catheter-induced aortic vegetations.
AB  - Staphylococcus aureus is the leading cause of infective endocarditis (IE). While
      the role of S. aureus cell-wall associated protein clumping factor A (ClfA) in
      promoting IE has been already demonstrated, that of the secreted plasma-clotting
      factors staphylocoagulase (Coa) and von Willebrand factor-binding protein (vWbp)
      has not yet been elucidated. We investigated the role of Coa and vWbp in IE
      initiation in rats with catheter-induced aortic vegetations, using Lactococcus
      lactis expressing coa, vWbp, clfA or vWbp/clfA, and S. aureus Newman Deltacoa,
      DeltavWbp, DeltaclfA or Deltacoa/DeltavWbp/DeltaclfA mutants. vWbp-expression
      increased L. lactis valve infection compared to parent and coa-expressing strains
      (incidence: 62%, versus 0% and 13%, respectively; P < 0.01). Likewise, expression
      of clfA increased L. lactis infectivity (incidence: 80%), which was not further
      affected by co-expression of vWbp. In symmetry, deletion of the coa or vWbp genes
      in S. aureus did not decrease infectivity (incidence: 68 and 64%, respectively)
      whereas deletion of clfA did decrease valve infection (incidence: 45%; P = 0.03
      versus parent), which was not further affected by the triple deletion
      Deltacoa/DeltavWbp/DeltaclfA (incidence: 36%; P > 0.05 versus DeltaclfA mutant).
      Coa does not support the initial colonization of IE (in L. lactis) without other
      key virulence factors and vWbp contributes to initiation of IE (in L. lactis) but
      is marginal in the present of ClfA.

PMID- 30280968
TI  - Preparation of Immunotolerant Space under the Skin and Transplantation of Islets
      in the Pockets.
AB  - A method which realizes allogeneic islets transplantation into a subcutaneous
      site under no immunosuppressive treatment has been desired for the treatment of
      type 1 diabetes. In this study, two donor-recipient combinations were employed:
      F344 rat donors (RT-1<sup>lv1</sup>) and ACI rat recipients (RT-1<sup>a</sup>);
      and Wistar rat donors (closed colony) and Lewis rat recipients (RT
      1<sup>l</sup>). An agarose rod , which carried basic fibroblast growth factor
      (bFGF; 50 MUg/rod, agarose-bFGF rod), was implanted into each of two dorsal
      subcutaneous sites of a streptozotocin induced diabetic rat for 7 days, and the
      space was formed by removal of the rod. 1500 allogeneic islets were transplanted
      into each of the subcutaneous spaces. No immunosuppressive medication was given
      before or after islet transplantation. The immunological analyses of the
      granulomatous tissue formed by agarose-bFGF rod were carried out with flow
      cytometry and gene expression to get some information for mechanism of acceptance
      of allogeneic islets. Subcutaneous spaces surrounded with highly vascularized
      granulomatous tissue were formed by agarose-bFGF rod implantation for 7 days. All
      recipients demonstrated long-term nomoglycemia (>100 days) in both donor
      recipient combinations. The percentages of regulatory T (Treg) cells/CD4 cells in
      the granulomatous tissue increased by the implantation of agarose-bFGF rod and
      the percentages remained high after islet transplantation. In addition,
      expression levels of genes associated with chemotaxis and induction of Treg cells
      increased in the granulomatous tissue by the implantation of agarose-bFGF rod.
      The agarose-bFGF rod implantation is a useful method for preparation of
      immunotolerant site for successful allogeneic islet transplantation without
      immunosuppressive medication, and Treg cells might play a pivotal role in the
      graft acceptance.

PMID- 30280969
TI  - 'In the Islands people don't really talk about this stuff, so you go through life
      on your own': An arts-based study exploring intimate relationships with young
      people in Samoa.
AB  - This study explores conceptualisations and understandings of intimate
      relationships with young people in Samoa - an at-risk group experiencing high
      rates of intimate partner violence and alienation from sexual and relationship
      health promotion. Insights contribute to the immediate need to advance knowledge
      and practice around prevention with this group. An arts-based approach, which
      included a two-day interactive drama workshop coupled with follow-up, peer-led
      focus groups, was used to explore perceptions and understandings related to
      intimate relationships with 15 tertiary educated young people (nine female and
      six male) from across Samoa. Intersectionality informed the data collection and
      thematic analysis, examining participants' lived experiences and the ways
      multiple and intersecting identities interact within social and cultural systems
      to influence and inform these experiences. Outcomes highlight important tensions
      for young people, including the way in which age, gender, religion and sexuality
      interact with social hierarchies and power structures, socially prescribed gender
      norms, family structures and globalisation. This research provides insights that
      can inform the development of prevention strategies to address the root causes of
      intimate partner violence, building the knowledge and skills required for
      establishing intimate relationships free from violence with young people.

PMID- 30280970
TI  - Normative Interlimb Impedance Ratios: Implications for Early Diagnosis of Uni-
      and Bilateral, Upper and Lower Limb Lymphedema.
AB  - BACKGROUND: Bioimpedance spectroscopy detects unilateral lymphedema if the ratio
      of extracellular fluid (ECF) between arms or between legs is outside three
      standard deviations (SDs) of the normative mean. Detection of bilateral
      lymphedema, common after bilateral breast or gynecological cancer, is complicated
      by the unavailability of an unaffected contralateral limb. The objectives of this
      work were to (1) present normative values for interarm, interleg, and arm-to-leg
      impedance ratios of ECF and ECF normalized to intracellular fluid (ECF/ICF); (2)
      evaluate the influence of sex, age, and body mass index on ratios; and (3)
      describe the normal change in ratios within healthy individuals over time.
      METHODS: Data from five studies were combined to generate a normative data set (n
      = 808) from which mean and SD were calculated for interarm, interleg, and arm-to
      leg ratios of ECF and ECF/ICF. The influence of sex, age, and body mass index was
      evaluated using multiple linear regression, and normative change was calculated
      for participants with repeated measures by subtracting their lowest ratio from
      their highest ratio. RESULTS: Mean (SD) interarm, interleg, dominant arm-to-leg,
      and nondominant arm-to-leg ratios were 0.987 (0.067), 1.005 (0.072), 1.129
      (0.160), and 1.165 (0.174) for ECF ratios; and 0.957 (0.188), 1.024 (0.183),
      1.194 (0.453), and 1.117 (0.367) for ECF/ICF ratios, respectively. Arm-to-leg
      ratios were significantly affected by sex, age, and body mass index. Mean
      normative change ranged from 7.2% to 14.7% for ECF ratios and from 14.7% to 67.1%
      for ECF/ICF ratios. CONCLUSION: These findings provide the necessary platform for
      extending bioimpedance-based screening beyond unilateral lymphedema.

PMID- 30280971
TI  - Video-assisted thoracoscopic surgery for the treatment of pericardial hydatid
      cyst.
AB  - INTRODUCTION: We would like to present video-assisted thoracoscopic surgery for
      the treatment of pericardial hydatid cyst. PATIENT AND METHOD: Thirty two-year
      old female patient was referred for evaluation of a left mediastinal mass.
      Magnetic resonance image, computed tomography and transesophageal
      echocardiography confirmed a well circumscribed mass with compatible hydatid cyst
      at the left pericardial wall end of the differantial diagnosis. Our surgical plan
      entailed the endoscopic resection of pericardial hydatid cyst. We did not adopt a
      more precise strategy such as open procedure. We managed removal of the hydatid
      cyst by using video assisted thoracoscopic surgery. RESULTS: The patient has been
      doing well for 4 years now after her surgery. CONCLUSION: We think that
      endoscopic approach is an effective treatment modality for pericardial hydatid
      cyst.

PMID- 30280972
TI  - Dynamic culture substrates that mimic the topography of the epidermal-dermal
      junction.
AB  - The junction between the epidermal and dermal layers of human skin undulates, the
      width and depth of the undulations varying with age and disease. We previously
      showed that when primary human epidermal keratinocytes are seeded on collagen
      coated undulating static polydimethylsiloxane (PDMS) elastomer substrates, the
      stem cells, differentiated cells and proliferating cells become patterned in
      response to cues from the underlying substrate. To investigate how patterning
      occurs over time, we have now created a dynamic model, in which a collagen-coated
      PLGA membrane is placed over a polyimide sheet containing circular holes,
      differing in diameter and spacing. When a vacuum is applied the membrane is
      induced to undulate, the heights of the undulations depending on the pressure
      applied and the size of the holes. We observed clustering of cells with high
      levels of beta1 integrin expression, a stem cell marker, in the base of the
      undulations within 48h of applying the vacuum. Differentiating, involucrin
      positive cells did not cluster; however, there was clustering of cells with high
      E-cadherin expression and nuclear YAP. Rho kinase inhibition resulted in loss of
      clustering, implicating a role for Rho family members in the process.

PMID- 30280973
TI  - Seeding the gender revolution: Women's education and cohort fertility among the
      baby boom generations.
AB  - In Europe and the United States, women's educational attainment started to
      increase around the middle of the twentieth century. The expected implication was
      fertility decline and postponement, whereas in fact the opposite occurred. We
      analyse trends in the quantum of cohort fertility among the baby boom generations
      in 15 countries and how these relate to women's education. Over the 1901-45
      cohorts, the proportion of parents with exactly two children rose steadily and
      homogeneity in family sizes increased. Progression to a third child and beyond
      declined in all the countries, continuing the ongoing trends of the fertility
      transition. In countries with a baby boom, and especially among women with post
      primary education, this was compensated for by decreasing childlessness and
      increasing progression to a second child. These changes, linked to earlier stages
      of the fertility transition, laid the foundations for later fertility patterns
      associated with the gender revolution.

PMID- 30280974
TI  - Intrathoracic hooked wire migration managed by minimally invasive thoracoscopic
      surgery.
AB  - BACKGROUND: Needle-guided localization wire is widely used to locate non-palpable
      breast lesion before surgery. A rare complication of this technique is wire
      migration. We report a case of an intrathoracic hooked wire migration in a 41
      year-old female treated by video-assisted thoracoscopic surgery (VATS). METHODS:
      We report a recent patient history and we review the cases reported in the
      literature. RESULTS: Hook removal by thoracoscopy seemed to be the less invasive
      and most effective approach for this stable case. Even asymptomatic migration
      should be treated, and the device removed. The less invasive approach can be
      considered after estimating the risk and best possible timing. CONCLUSION: The
      loss of a hooked wire can lead to dramatic lesions. In every case, the device
      must be found or, if not, migration ruled out. The hooked wire must be removed,
      and the timing and the approach must be adapted to each case. VATS should be
      considered, in a stable patient to assess the lesions, to treat them and to
      remove the device.

PMID- 30280975
TI  - Community perceptions of obstetric fistula in Malawi.
AB  - It is well-documented that obstetric fistula, a severe birth injury, is caused by
      a prolonged obstructed labour that has not been relieved on time. Lay people
      often understand causation differently. This study sought to explore the
      awareness and local meanings attached to obstetric fistula in the rural parts of
      Malawi. We conducted interviews with key informants and focus group discussions
      with community members in purposively selected communities in the central region
      of Malawi. We categorised data using Nvivo 10 and conducted a thematic analysis.
      Findings indicate that there is considerable awareness about fistula in local
      communities; however, community members have very limited knowledge about its
      causes. Participants associated obstetric fistula with sexually transmitted
      diseases, the woman's laziness to push during labour, witchcraft and the
      husband's infidelity, which contributed to the isolation of the affected women.
      Strategies to eradicate obstetric fistula in general, and its social consequences
      in particular, should include more information on causes and prevention. This may
      help to dispel misconceptions about fistula, increase acceptance and support for
      women with fistula, and subsequently improve the quality of their lives and the
      lives of girls and women who may suffer from this condition in the future.

PMID- 30280976
TI  - Pick-up Impression of Complete Arch Implant-supported Interim Prosthesis.
AB  - Not required.

PMID- 30280977
TI  - An Interview with Michele De Luca.

PMID- 30280978
TI  - Gene and Cell Therapy: Tearing Down Walls.

PMID- 30280979
TI  - Spring Forward: ESGCT Trains the Next Generation of Gene and Cell Therapists.

PMID- 30280980
TI  - Pharmacological Stimulation of Mitochondrial Biogenesis Using the Food and Drug
      Administration-Approved beta2-Adrenoreceptor Agonist Formoterol for the Treatment
      of Spinal Cord Injury.
AB  - A hallmark of the progressive cascade of damage referred to as secondary spinal
      cord injury (SCI) is vascular disruption resulting in decreased oxygen delivery
      and loss of mitochondria homeostasis. While therapeutics targeting restoration of
      single facets of mitochondrial function have proven largely ineffective
      clinically post-SCI, comprehensively addressing mitochondrial function via
      pharmacological stimulation of mitochondrial biogenesis (MB) is an underexplored
      strategy. This study examined the effects of formoterol, a mitochondrial biogenic
      Food and Drug Administration-approved selective and potent beta2-adrenoreceptor
      (ADRB2) agonist, on recovery from SCI in mice. Female C57BL/6 mice underwent
      moderate SCI using a force-controlled impactor-induced contusion model, followed
      by daily formoterol intraperitoneal administration (0.1 mg/kg) beginning 1 h post
      SCI. The SCI resulted in decreased mitochondrial protein expression, including
      PGC-1alpha, in the injury and peri-injury sites as early as 3 days post-injury.
      Formoterol treatment attenuated this decrease in PGC-1alpha, indicating enhanced
      MB, and restored downstream mitochondrial protein expression to that of controls
      by 15 days. Formoterol-treated mice also exhibited less histological damage than
      vehicle-treated mice 3 days after injury-namely, decreased lesion volume and
      increased white and gray matter sparing in regions rostral and caudal to the
      injury epicenter. Importantly, locomotor capability of formoterol-treated mice
      was greater than vehicle-treated mice by 7 days, reaching a Basso Mouse Scale
      score two points greater than that of vehicle-treated SCI mice by 15 days.
      Interestingly, similar locomotor restoration was observed when initiation of
      treatment was delayed until 8 h post-injury. These data provide evidence of ADRB2
      mediated MB as a therapeutic approach for the management of SCI.

PMID- 30280981
TI  - Exploring Cross-Sectional Predictors of Suicide Ideation, Attempt, and Risk in a
      Large Online Sample of Transgender and Gender Nonconforming Youth and Young
      Adults.
AB  - PURPOSE: Rates of suicide ideation and attempt appear to be particularly high in
      the transgender and gender nonconforming (TGNC) population, yet little is known
      about which factors are the most salient contributors for TGNC young people and
      how these contributors vary across suicide-related outcomes. METHODS: Within the
      largest sample of TGNC young people to date (N = 1896; ages 14-30), we examined
      the contribution of demographics (age, assigned sex, gender identity, sexual
      orientation identity, race/ethnicity, and socioeconomic status), minority stress
      (gender-related affirmation, gender-related self-concept, victimization, and
      gender-affirming medical treatment desire/access), social support (from family
      and friends), and depressive symptoms in the cross-sectional prediction of three
      suicide-related outcomes: past-year attempt, past-year ideation, and a composite
      measure of suicide risk. RESULTS: Each set of factors explained significant
      variance in each outcome; however, only several predictors remained significant
      in each of the full models. Gender-related victimization and depressive symptoms
      were independent predictors for all three outcomes. Additional predictors varied
      across outcome. Age, male identity, sexual orientation-based victimization, and
      friend support were associated with suicide attempt. Age, queer identity, gender
      related self-concept negativity, and family support were associated with suicide
      ideation, and pansexual identity and gender-related self-concept negativity were
      associated with positive suicide risk screen. CONCLUSION: Prevention and
      intervention efforts aimed at building support and positive self-concept,
      decreasing victimization, and treating depression are likely to partially reduce
      suicide ideation and attempt in TGNC adolescents and young adults. Comprehensive
      interventions with younger adolescents are particularly critical.

PMID- 30280982
TI  - Characterization of a tubular electrochemical reactor for the degradation of the
      commercial diuron herbicide.
AB  - After designing and constructing an electrochemical reactor with concentric
      electrodes and tangential feed (RECT), it is necessary to characterize it and to
      study its performance. The experimental study of the residence time distribution
      (RTD) was conducted for flow rates of 2.78 * 10-6 m3 s-1, 8.33 * 10-6 m3 s-1 and
      13.9 * 10-6 m3 s-1. According to the values obtained from the Pe number (0.67
      1.52), the RECT fits as tubular with great dispersion. The determined empirical
      correlation (Sh = 18.16 Re0.50 Sc0.33) showed a laminar flow behavior in the
      range of Reynolds number (Re) between 23 and 117. In order to use RECT in
      effluent treatment, an electrochemical oxidation study of the Diuron model
      molecule (Nortox(r)) was performed to analyze reactor performance in a closed
      system with total reflux. A decay kinetics of pseudo-first order was associated
      with the decay of the concentration of diuron and 30% mineralization in 180 min
      of process were obtained, having a total volume of 4 * 10-3 m3 and an initial
      concentration of commercial Diuron in 215.83 mg dm-3. Eleven by-products were
      identified by HPLC-MS analysis and, from this, it was possible to propose a route
      of degradation of the diuron. From these observations, it can be inferred that
      the studied electrochemical reactor had applicability in the degradation of
      recalcitrant compounds, as is the case of commercial diuron. Make some changes in
      the electrochemical reactor studied and other advanced oxidative processes, such
      as electro-Fenton, can be associated with the studied system to achieve a better
      conversion efficiency.

PMID- 30280983
TI  - What Accounts for Prosocial Behavior? Roles of Moral Identity, Moral Judgment,
      and Self-Efficacy Beliefs.
AB  - Prior research suggests that moral identity influences individuals' willingness
      to engage in prosocial behavior. Little attention, however, has been given to the
      roles of and relations between moral identity and other factors, such as moral
      judgment, in accounting for types of prosocial behavior in adolescence. The
      current study examined the extent to which moral identity, moral judgment, and
      social self-efficacy contribute to prosocial behaviors in adolescence.
      Approximately 338 adolescents (Mage = 13.4 years) completed measures of moral
      identity, moral judgment, social self-efficacy, and prosocial behavior. Teachers
      rated adolescents' prosocial behaviors, which largely corroborated the
      adolescents' self-reports. Moral identity was found to predict most types of
      prosocial behavior. Moral judgment and moral identity were related and jointly
      predicted altruistic prosocial behaviors, but did not predict helping in front of
      others. Further, moral identity mediated the relationships between moral judgment
      and some forms of prosocial behavior (e.g., emotional, volunteering). Self
      efficacy beliefs were found to predict some types of prosocial behavior (e.g.,
      public), perhaps providing adolescents with confidence to engage in prosocial
      action. Overall, moral identity was especially effective in directly accounting
      for prosocial behavior, and may act as a mediator to bridge the moral judgment
      moral action gap among adolescents.

PMID- 30280984
TI  - John Tompkins Lyman (May 25, 1932 - May 30, 2018).

PMID- 30280985
TI  - Radiation-Drug Combinations to Improve Clinical Outcomes and Reduce Normal Tissue
      Toxicities: Current Challenges and New Approaches: Report of the Symposium Held
      at the 63rd Annual Meeting of the Radiation Research Society, 15-18 October 2017;
      Cancun, Mexico.
AB  - The National Cancer Institute's (NCI) Radiation Research Program (RRP) is
      endeavoring to increase the relevance of preclinical research to improve outcomes
      of radiation therapy for cancer patients. These efforts include conducting
      symposia, workshops and educational sessions at annual meetings of professional
      societies, including the American Association of Physicists in Medicine, American
      Society of Radiation Oncology, Radiation Research Society (RRS), Radiosurgery
      Society, Society of Nuclear Medicine and Molecular Imaging, Society for
      Immunotherapy of Cancer and the American Association of Immunology. A symposium
      entitled "Radiation-Drug Combinations to Improve Clinical Outcomes and Reduce
      Normal Tissue Toxicities" was conducted by the NCI's RRP during the 63rd Annual
      Meeting of the RRS on October 16, 2017 in Cancun, Mexico. In this symposium,
      discussions were held to address the challenges in developing radiation-drug
      combinations, optimal approaches with scientific evidence to replace standard-of
      care, approaches to reduce normal tissue toxicities and enhance post-treatment
      quality-of-life and recent advances in antibody-drug conjugates. The symposium
      included two broad overview talks followed by two talks illustrating examples of
      radiation-drug combinations under development. The overview talks identified the
      essential preclinical infrastructure necessary to accelerate progress in the
      development of evidence and important challenges in the translation of drug
      combinations to the clinic from the laboratory. Also addressed, in the example
      talks (in light of the suggested guidelines and identified challenges), were the
      development and translation of novel antibody drug conjugates as well as
      repurposing of drugs to improve efficacy and reduce normal tissue toxicities.
      Participation among a cross section of clinicians, scientists and scholars-in
      training alike who work in this focused area highlighted the importance of
      continued discussions to identify and address complex challenges in this emerging
      area in radiation oncology.

PMID- 30280986
TI  - A Woman'S Status and Prenatal Care Utilization in Patrilocal Households of Post
      Soviet Countries.
AB  - Women's household autonomy is associated with maternal healthcare utilization in
      developing countries, but its effects are not consistently positive. In the
      current study, the researchers test prenatal care utilization in Armenia and
      Azerbaijan (N = 2,159). After controlling for socioeconomic factors, we find that
      women's autonomy seems to be a mixed blessing. For instance, participating in
      daily purchases delays the start of prenatal care, but results in more prenatal
      care visits. Additionally, a woman's household position as a daughter-in-law has
      significant negative associations with accessing prenatal care during the first
      trimester of pregnancy.

PMID- 30280987
TI  - Vicarious Posttraumatic Growth in End-of-Life Care: How Filling Gaps in Knowledge
      Can Foster Clinicians' Growth.
AB  - Vicarious posttraumatic growth is a term used to describe the positive benefits
      from working with trauma patients who themselves have experienced a highly
      stressful or traumatic event and resultant growth. Research on vicarious
      posttraumatic growth remains in its initial stages and findings are inconsistent,
      leading to the need for additional research. A literature review was performed to
      ascertain the methodologies guiding research on vicarious posttraumatic growth
      and identify gaps in knowledge. This study found that 71% of research studies
      examined used survey instruments to measure vicarious posttraumatic growth and
      87% of these studies utilized the Posttraumatic Growth Inventory (alpha = 0.90).
      This instrument was not designed to measure secondary trauma. In order to support
      clinicians who are at high risk of adverse outcomes, the knowledge of vicarious
      posttraumatic growth must be broadened by conducting research with varying
      methodologies, among other populations, and by developing effective survey
      instruments to operationalize this concept.

PMID- 30280988
TI  - Egg Intake Has No Adverse Association With Blood Lipids Or Glucose In Adolescent
      Girls.
AB  - OBJECTIVE: Longitudinal data on cardiometabolic effects of egg intake during
      adolescence are lacking. The current analyses aim to evaluate the impact of usual
      adolescent egg consumption on lipid levels, fasting glucose, and insulin
      resistance during late adolescence (age 17-20 years). METHODS: Data from 1392
      girls, aged 9 to 10 at baseline and followed for 10 years, in the National Heart,
      Lung, and Blood Institute's National Growth and Health Study were used to examine
      the association between usual egg intake alone and in combination with other
      healthy lifestyle factors and late adolescent lipid levels, fasting glucose, and
      insulin resistance, measured as homeostasis model assessment of insulin
      resistance (HOMA-IR). Diet was assessed using 3-day food records during eight
      examination cycles. Girls were classified according to usual weekly egg intake,
      ages 9-17 years: <1 egg/wk (n = 361), 1 to <3 eggs/wk (n = 703), and >=3 eggs/wk
      (n = 328). Analysis of covariance modeling was used to control for confounding by
      other behavioral and biological risk factors. RESULTS: Girls with low, moderate,
      and high egg intakes had adjusted low-density lipoprotein cholesterol levels of
      99.7, 98.8, and 95.5 mg/dL, respectively (p = 0.0778). In combination with higher
      intakes of fiber, dairy, or fruits and vegetables, these beneficial effects were
      stronger and statistically significant. There was no evidence that >=3 eggs/wk
      had an adverse effect on lipids, glucose, or HOMA-IR. More active girls who
      consumed >=3 eggs/wk had the lowest levels of insulin resistance. CONCLUSION:
      These results suggest that eggs may be included as part of a healthy adolescent
      diet without adverse effects on glucose, lipid levels, or insulin resistance.

PMID- 30280989
TI  - Message and Delivery Preferences for Online Tobacco Education among Adolescents
      and Young Adults.
AB  - Use of cigarettes and noncigarette tobacco products (NCTPs) among adolescents and
      young adults remains high. Strategies to communicate the risks of cigarettes and
      NCTPs are needed. Online tobacco education is one such strategy; however, there
      is little guidance for message development. We conducted four focus groups (n =
      39) with adolescent and young adult to identify message and delivery preferences
      for online tobacco education. Participants evaluated three existing tobacco
      education websites. Transcripts were coded for preferred tobacco education
      message content, delivery, and willingness to use online tobacco education.
      Participants preferred novel, concise facts, embedded links to credible sources,
      and an anti-industry tone for website messages. Participants expressed an
      aversion to message strategies that relied on scare tactics or attempted to
      simulate youth media trends (e.g., overuse of hashtags). To increase exposure,
      participants recommended using social media to drive engagement. Results serve as
      guidelines for what information adolescents and young adults desire, as well as
      how they want this information communicated with online tobacco education. Our
      findings - youth prefer new, fact-based information that is conveyed concisely,
      with sources, without authoritative tones, and delivered via social media -
      provides guidance for how to develop online tobacco education for this at-risk
      population.

PMID- 30280990
TI  - Large Cytologically Benign Thyroid Nodules Do Not Have High Rates of Malignancy
      or False-Negative Rates and Clinical Observation Should be Considered: A Meta
      Analysis.
AB  - BACKGROUND: Management of large thyroid nodules is controversial, as data are
      conflicting regarding overall rates of malignancy (ROM) in all nodules and
      frequency of false-negative fine-needle aspiration results (FNR) in cytologically
      benign nodules. This meta-analysis aimed to evaluate and compare ROM and FNR in
      small versus large nodules published in the literature. METHODS: Articles indexed
      in PubMed, written in English, published electronically or in print on or prior
      to December 8 2017 were searched for "false negative thyroid size or cm" and
      "malignancy rates benign thyroid nodules." Three hundred fifty-two unique
      citations were identified. Multiple reviewers selected a final set of 35 articles
      that contained nodules stratified by size (3, 4, or 5 cm), with benign or all
      cytologic diagnoses, and with postsurgical histologic diagnoses. Multiple
      observers extracted data, including numbers of total, cytologically benign, and
      histologically malignant nodules. Size cutoffs of 3, 4, and/or 5 cm were analyzed
      in 14, 24, and 1 article, respectively. RESULTS: ROM in all nodules >=3 cm
      (13.1%) and >=4 cm (20.9%) was lower than those <3 cm (19.6%) and <4 cm (19.9%;
      odds ratio [OR] = 0.72 [confidence interval (CI) 0.64-0.81] and OR = 0.85 [CI
      0.77-0.95]). FNR in nodules >=3 cm (7.2%) was not different from smaller nodules
      (5.7%; OR = 1.47 [CI 0.80-2.69]). FNR in nodules >=4 cm (6.7%) was slightly
      higher than those <4 cm (4.5%; OR = 1.38 [CI 1.06-1.80]). The most frequently
      reported false-negative diagnosis was papillary thyroid carcinoma. CONCLUSIONS:
      Rates of malignancy and false-negative FNA results vary but, in most studies, are
      not higher in larger nodules. Patients with large, cytologically benign thyroid
      nodules need not undergo immediate surgical resection, as false-negative FNA
      rates are low and are expected to decrease in light of nomenclature revision of a
      subset of follicular variants of papillary thyroid carcinoma.

PMID- 30280995
TI  - Misreporting of Energy Intake in Older People: Comparison of Two Dietary
      Assessment Methods.
AB  - Accurate assessment of dietary intake is essential in clinical practice and
      research. While energy intake (EI) misreporting has been extensively studied in
      the general population, relatively little is known about misreporting among older
      people. This cross-sectional study used clinical data routinely collected in 127
      participants, aged 70-96 years, from the Toulouse Frailty Clinic. EI was assessed
      by diet history interview and three-day food record. Misreporters were identified
      with the Goldberg cut-off method, using the Harris-Benedict equation to estimate
      total energy expenditure. The response rate was 66% for three-day food record and
      93% for diet history interviews. EI from diet history interviews (1799 +/- 416
      kcal/day) was significantly higher than from food records (1400 +/- 381 kcal/day;
      p < 0.001) and closest to total energy expenditure (1758 +/- 437 kcal/day; (p >
      0.05). Thirty percent of participants were identified as underreporters with
      three-day food records vs. 9% with diet history interviews. Overreporters were
      found with diet history interviews only (11% of participants). In older people,
      the diet history interview has the advantage of obtaining a higher response rate
      and a lower underreporting rate, compared to three-day food record. Nevertheless,
      with this method, overreporting was observed and interpreting results should be
      done with caution.

PMID- 30280996
TI  - From Food for Survival to Food for Personalized Optimal Health: A Historical
      Perspective of How Food and Nutrition Gave Rise to Nutrigenomics.
AB  - Human nutrition has progressed impressively from the hunter-gatherer mode to that
      of promising personalized nutrition for health optimization through advanced and
      sophisticated omics technologies. The contemporary major diseases, while having
      strong genetic components, do not conform to Mendelian genetics; hence, their
      expression/manifestation is not controlled by a single gene. Noncommunicable
      diseases such as obesity, cancer, type 2 diabetes mellitus, and cardiovascular
      disease are attributed to a series of chronic anomalies closely related to
      dietary, among other, environmental factors, and consistent deregulation of one
      or more groups of genes (polygenic). Collectively, these diseases constitute the
      main cause of death globally and pose tremendous financial burden on healthcare
      systems. Dietary interventions offer significant possibilities for cost-effective
      strategies to reduce risk of a series of metabolic diseases and/or improve the
      outcome of prognosis. In recent decades, the ability of particular nutrients to
      influence certain cellular functions as well as the regulation of several
      metabolic pathways via genomic interplay has been demonstrated. Nutrients can
      influence cellular responses and hence exert an effect on health parameters and
      outcomes. Several nutrients have been documented to extend their regulatory
      capacity at various levels including gene expression profile signatures'
      modulation. In addition, specific nutrients can modulate expression/activation of
      genes that encode regulatory hormones, which in turn are signaling agents
      strongly affecting metabolism and subsequently risk levels for certain metabolic
      diseases. The field of nutrigenomics attempts to revolutionize modern thinking on
      diet, food, and health; whether it will deliver is still an open matter of debate
      Key teaching points: A brief, yet comprehensive account on how food and nutrition
      evolved to give rise to nutrigenomics. Discusses potential of nutrigenomics for
      public health contribution in noncommunicable diseases. Debates credibility of
      nutrigenomics' commercial products versus the bio-hype in the field. Presents
      experts' and stakeholders' opinions for future directions of nutrigenomics.

PMID- 30280998
TI  - Applying the Health Belief Model to Medication Adherence: The Role of Online
      Health Communities and Peer Reviews.
AB  - Millions of Americans are living with at least one chronic disease, and while the
      majority has been prescribed medication to control symptoms-medication adherence
      is a widespread problem. Medication nonadherence varies by chronic disease,
      patient characteristics, and insurance coverage, and previous research has
      identified non-financial barriers including disease-related knowledge, health
      literacy and polypharmacy. However, given the increasing popularity of online
      health communities, little research examines the influence of user-generated
      content on health behaviors. Many patients use the internet to seek and share
      information related to prescription medications. The current study examines
      patients' attitudes and behavioral intentions formed (in part) by the user
      generated content exchanged within online health communities. Specifically, the
      Health Belief Model's perceived barriers and perceived benefits are explored
      here. Twenty members from online health communities related to arthritis are
      interviewed to understand how peer-to-peer communication is used in regards to
      medication adherence. Three themes emerged from the data, including striving for
      pain relief, negotiating potential side effects, and finding the new normal.
      Theoretical and practical implications are discussed.

PMID- 30280997
TI  - Use of Mental Health Services Among College Students by Sexual Orientation.
AB  - PURPOSE: The current study examines differences between lesbian, gay, bisexual,
      and questioning (LGBQ) students and heterosexual students in terms of counseling
      and mental health services received (healthcare utilization), from whom students
      would seek help, and who contributed positively to students' ability to cope
      during a stressful period. METHODS: An online survey was administered among
      25,844 college students, enrolled in 76 schools (mean age = 25.52). The majority
      of participants was graduate students (42.81%) and reported their race/ethnicity
      as non-Hispanic White (70.49%). RESULTS: Compared with their heterosexual
      counterparts, gay males and lesbian/gay and bisexual females reported receiving
      more counseling or mental health services, most notably from counselors,
      therapists, psychologists, and/or social workers. Bisexual males and LGBQ females
      were less likely to seek help from a parent or family member compared with
      heterosexual males and females, respectively. Racial/ethnic minority bisexual
      females were less likely to seek help from a friend or roommate than non-Hispanic
      White bisexual females. Compared with their heterosexual counterparts, gay and
      questioning males and LGBQ females were more likely to report that religion
      reduced their ability to cope. CONCLUSION: The current findings illuminate
      important differences by sexual orientation in terms of seeking and receiving
      mental health services. Although we found that lesbian/gay and bisexual college
      students were more likely to receive counseling and mental healthcare, we cannot
      ascertain whether they were satisfied with the services they received. The
      findings also suggest that certain groups of LGBQ students do not find support
      with their clergy and family, which may indicate a lack of understanding or
      acceptance of LGBQ issues.

PMID- 30280999
TI  - Intravital Imaging for Tracking of Angiogenesis and Cellular Events Around
      Surgical Bone Implants.
AB  - IMPACT STATEMENT: These new experimental methods allow us to image, and quantify,
      angiogenesis and perivascular cell dynamics in the endosseous healing
      compartment. As such, the method is capable of providing a new perspective on,
      and unique information regarding, healing that occurs around orthopedic and
      dental implants.

PMID- 30281000
TI  - Towards Health Equity: Deaf Adults' Engagement in Social e-Health Activities and
      e-Communication with Health Care Providers.
AB  - Deaf people face significant barriers with accessing health information, health
      care services, and communication with their health care provider and as a result,
      show poorer health outcomes compared to the general population. Studies on the
      general population found that those who use social network sites (SNS) for health
      related activities were more likely to communicate with their health care
      provider via the Internet or email. For deaf individuals who use American Sign
      Language (ASL), using eHealth platforms to communicate with health care providers
      has the potential to navigate around communication barriers and create greater
      opportunity to discuss screening and treatment plans. Using national data from
      the HINTS-ASL survey, we explored whether engagement in social eHealth activities
      on SNS is linked to electronic communication with health care providers after
      controlling for deaf patient characteristics. Our sample for this study consisted
      of 515 deaf participants who reported using (social media/SNS) to read and share
      health information. Controlling for sociodemographic variables, participants who
      engaged in social eHealth activity were threefold more likely to communicate with
      their healthcare provider electronically. Using eHealth platforms for social
      health engagement demonstrates potential to reduce health inequality among deaf
      people.

PMID- 30281002
TI  - Legends in Urology.

PMID- 30281001
TI  - Why Doesn't Everyone Want To Be A Urologist, Our Tomorrows Will Be Better Than
      Our Yesterdays.

PMID- 30281003
TI  - Prostate Cancer: Clinical Case Scenarios.

PMID- 30281004
TI  - Cystectomy for benign disease: readmission, morbidity, and complications.
AB  - INTRODUCTION: We sought to elucidate outcomes and risks associated with
      cystectomy and urinary diversion for benign urological conditions compared to
      malignant conditions. MATERIALS AND METHODS: We identified patients who underwent
      cystectomy and urinary diversion for benign and malignant diseases through the
      American College of Surgeons National Surgery Quality Improvement Program
      database for the period 2007-2015. Patients were selected for inclusion based
      upon their current procedure terminology and International Classification of
      Disease, Ninth revision codes. Primary outcome was 30 day morbidity including
      return to the operating room (OR); infectious, respiratory, and/or cardiovascular
      complications; readmission to the hospital; and mortality. Multivariable
      regression analyses were performed to identify associated factors. RESULTS: A
      total of 317 patients underwent cystectomy and urinary diversion for benign
      disease, and 5510 patients underwent radical cystectomy with urinary diversion
      for cancer. Rates of major morbidity (43.2% versus 38.6%), mortality (0.9% versus
      1.9%), return to OR (5% versus 5.8%), readmission (19.7% versus 21.4%),
      postoperative sepsis (14.5% versus 12%), and wound complications (16.1% versus
      14.2%) were similar among patients undergoing cystectomy for benign and malignant
      conditions. In the group with cystectomy for benign conditions, smoking (OR:
      3.11) and longer operative duration (OR: 1.06) were significantly associated with
      increased overall morbidity. Wound complications were significantly higher in
      smokers (OR: 3.09) and with an ASA >= III (OR: 5.71) CONCLUSIONS: Patients
      undergoing cystectomy and urinary diversion for benign disease are at similar
      risk for 30 day morbidity and mortality as patients undergoing surgery for
      malignant conditions. Risk factors are identified that can potentially be
      targeted for morbidity reduction.

PMID- 30281005
TI  - Health-related quality of life after BCG or MMC induction for non-muscle invasive
      bladder cancer.
AB  - INTRODUCTION: To evaluate health-related quality of life (HRQoL) in patients with
      non-muscle invasive bladder cancer (NMIBC) during the induction phase of
      intravesical instillations with BCG or MMC. MATERIALS AND METHODS: HRQoL was
      measured by two questionnaires from EORTC (QLQ-C30 and QLQ-BLS24), stratifying
      results by gender, age and therapy at the start of the therapy (T0), at last
      instillation (T1) and at 3 months after T1 (T2). The persistence of QoL-related
      side effects after 3 months from the end of the induction cycle was evaluated.
      RESULTS: We enrolled 108 naive patients and 103 patients self-completed the
      questionnaires. Treatment was well tolerated in both groups. Side effects were
      reported by 46.6% of patients at T1 and 47.5% of patients at T2. QoL dropped at
      T1, returning to the baseline at T2. Drop of QoL was greater in the physical,
      role, emotional and social functioning domains and in some clinical domains as
      pain, fatigue and insomnia. Our stratified analysis showed that patients > 70
      years have a worsening of QoL, a higher incidence of patient-reported side
      effects or symptoms in the BCG arm as compared to MMC arm. CONCLUSIONS: Our study
      shows that intravesical instillations of BCG or MMC during the induction phase
      might have a relevant effect on HRQoL.

PMID- 30281006
TI  - Assessment of practices in screening and treating women with bacteriuria.
AB  - INTRODUCTION: Evidence-based screening and treatment for bacteriuria is crucial
      to prevent increasing antibiotic resistance. The Infectious Disease Society of
      America (IDSA) previously released guidelines on the management of asymptomatic
      bacteriuria (ASB) and uncomplicated urinary tract infections (UTIs) in women. The
      study's objective was to assess physicians' practices in managing women with
      bacteriuria relative to these guideline recommendations. MATERIALS AND METHODS:
      Cross-sectional data from physicians were collected using an anonymous
      questionnaire. Multivariable logistic regression analyses identified independent
      predictors of adherence to guidelines. RESULTS: Data were collected from 260
      physicians. Over half of physicians surveyed were unfamiliar with IDSA guidelines
      and overtreat ASB. Variables independently associated with overtreatment of ASB
      included a non-academic practice and practicing as an OBGYN. Nearly one third
      (30.1%) of physicians reported prescribing an antibiotic other than a recommended
      first-line agent for uncomplicated cystitis. Relative to internists, OBGYNs and
      urologists were more likely to prescribe a recommended first-line agent to women
      with uncomplicated cystitis. Of those who correctly selected a first-line agent,
      29.8% prescribed a longer than recommended duration of therapy. IDSA guideline
      awareness was not associated with physicians' practices in managing women with
      bacteriuria. CONCLUSIONS: Most physicians surveyed were unfamiliar with
      guidelines related to managing ASB and uncomplicated UTIs in women, likely
      contributing to overscreening and overtreatment of ASB and the use of
      inappropriate antibiotic regimens in treating uncomplicated cystitis. However,
      optimal antibiotic prescribing was not associated with knowledge of IDSA
      guidelines, suggesting that guideline dissemination alone may not alter practice
      patterns among physicians managing women with bacteriuria.

PMID- 30281007
TI  - Nephrostomy tube placement prior to percutaneous nephrolithotomy does not impact
      outcomes.
AB  - INTRODUCTION: This study aims to compare outcomes of percutaneous nephrolithotomy
      (PCNL) performed with a nephrostomy tube placed prior to surgery versus access at
      the time of surgery. MATERIALS AND METHODS: Between March 2005 and August 2014,
      233 PCNLs were performed. One hundred and nine of those cases underwent placement
      of nephrostomy tubes at least 1 day prior to surgery (Group A), and the remaining
      124 cases were performed in which access was obtained at the time of PCNL (Group
      B). Patient demographics, comorbidities, stone size, sepsis rates, and additional
      complication rates including bleeding and inability to access stone were
      compared. RESULTS: There were no significant differences in patient demographics,
      stone size, or comorbidities when comparing the two groups. Success rates were
      not significantly different, 92.7% in Group A compared to 94.4% in Group B.
      Similarly, there was no significant difference in complication rates or ICU
      admissions. The rate of sepsis in Group A was 1.83% compared to 2.42% in Group B,
      which showed no statistical significance. Notably, there were more patients with
      neurogenic bladders in the pre-placement group (p = 0.05). CONCLUSION: Pre
      placement of a nephrostomy tube prior to PCNL did not result in a decreased
      incidence of complications or sepsis and did not demonstrate increased success
      rates. Patients with neurogenic bladders may be more vulnerable to suffering from
      sepsis and therefore role of timing of nephrostomy tube placement must be further
      studied.

PMID- 30281008
TI  - Laparoscopic heminephrectomy for duplex system: observed difference in outcomes
      between upper and lower pole resections.
AB  - INTRODUCTION: Renal duplication is a relatively common congenital abnormality of
      the urinary tract, but symptomatic duplex kidney is a rare presentation in
      adults. Traditionally, the treatment of choice for poorly functioning moiety has
      been heminephrectomy. There is extensive literature detailing the outcomes of
      minimally invasive upper pole heminephrectomy, but comparatively little published
      regarding lower pole resection, especially in adult patients. We present a series
      of 13 patients who underwent minimally invasive heminephrectomy for duplex
      kidney. MATERIALS AND METHODS: Over a 6 year period (2011-2017) 13 patients at a
      single center underwent laparoscopic heminephrectomy for symptomatic duplex
      kidney with a poorly functioning moiety. A retrospective review of case notes and
      imaging was undertaken. RESULTS: Eight and 5 patients underwent upper and lower
      pole heminephrectomies, respectively. Laparoscopic transperitoneal approach was
      utilized in all cases. Median length of stay was 2 days (range 1 to 16 days). In
      the upper pole cohort, one patient had a postoperative infection requiring IV
      antibiotics. In the lower pole cohort by contrast, there were three major
      complications (60%). Conversion to complete nephrectomy was necessary in one
      case; one patient had urinary leakage requiring selective embolization and one
      patient required a second operation to resect remnant calyces. Furthermore, two
      patients (40%) developed late recurrence of symptoms. CONCLUSIONS: Symptomatic
      duplex kidney is a rare presentation in adults. In our experience,
      heminephrectomy for non-functioning renal unit is safe and reproducible in
      experienced hands with no major complications and resolution of symptoms in the
      majority of patients. We have, however, observed a higher complication rate in
      those undergoing resection of a lower pole moiety. Alternative management such as
      uretero-ureterostomy should be considered in these cases.

PMID- 30281009
TI  - Impact of diabetes and metformin use on prostate cancer outcome of patients
      treated with radiation therapy: results from a large institutional database.
AB  - INTRODUCTION: Conflicting data exists on the influence of metformin on prostate
      cancer. We investigated the importance of metformin in patients treated with
      radiotherapy or brachytherapy. MATERIALS AND METHODS: All patients from a large
      institutionalized database, treated for primary localized prostate cancer with
      either brachytherapy or external-beam radiotherapy +/- androgen deprivation
      therapy were identified. Groups were compared by Kaplan-Meier analyses and Cox
      regression models. Multivariate analysis was adjusted for CAPRA-Score, type of
      treatment and age. RESULTS: A total of 2441 patients with complete data was
      identified. Among the 382 patients (16% of total) were diabetic. Two-hundred and
      eighty-one of the 382 diabetics (74%) were treated with metformin and 101 were
      treated with other anti-diabetic medication. Median follow up was 48 months
      (interquartile range [IQR] 24-84). Two-hundred eighteen patients (9%) died and
      150 (6%) experienced biochemical recurrence (BCR). On unadjusted univariate
      analysis for BCR-free survival, metformin users showed a 50% reduction in BCR
      compared to non-metformin users. The results remained significant on multivariate
      analysis comparing diabetic metformin users to non-metformin users (diabetics and
      non-diabetics combined) (hazard ratio [HR] 0.5-0.6, p = 0.03-0.04) but lost its
      significance when adjusting for cancer aggressiveness. On multivariate analysis,
      diabetics had worse overall survival (OS) than non-diabetics (HR 1.5, 95%
      confidence interval [CI] 1.08-2.06, p = 0.01), but diabetics on metformin fared
      better than diabetics not taking metformin (HR 0.5, 95% CI 0.26-0.86, p = 0.01).
      CONCLUSION: Metformin use in this analysis appears to be associated with better
      BCR and OS. Larger datasets and prospective trials are warranted to validate
      these results.

PMID- 30281010
TI  - Survival and secondary interventions following treatment for locally-advanced
      prostate cancer.
AB  - INTRODUCTION: The utility of radical prostatectomy (RP) for locally-advanced
      prostate cancer remains unknown. Retrospective data has shown equivalent
      oncologic outcomes compared to radiation therapy (RT). RP may provide local tumor
      control and prevent secondary interventions from local invasion, and may decrease
      costs. MATERIALS AND METHODS: Using SEER-Medicare data from 1995-2011 we
      identified men with locally-advanced prostate cancer undergoing RP or RT. Rates
      of post-treatment diagnoses and interventions were identified using ICD-9 and CPT
      codes. Skeletal related events (SRE), androgen deprivation therapy (ADT)
      utilization, all-cause mortality, prostate cancer-specific mortality, and costs
      were compared. RESULTS: A total of 8367 men with locally-advanced prostate cancer
      were identified (6200 RP, 2167 RT). RT was associated with increased urinary
      obstruction, hematuria, infection, and cystoscopic intervention while RP was
      associated with increased urethral stricture intervention and erectile
      dysfunction. Compared to RT, RP was associated with decreased all-cause mortality
      (3.1 versus 5.2 deaths/100-person-years, p < 0.001), prostate cancer-specific
      mortality (0.8 versus 2.0 deaths/100-person-years, p < 0.001), SREs (2.0 versus
      3.4 events/100 person-years, p < 0.001), and ADT utilization overall (7.4 versus
      33.8 doses/100-person-years, p < 0.001) and > 3 years after treatment (3.6 versus
      4.6 doses/100-person-years, p < 0.001). Overall and cancer specific costs were
      significantly lower for RP versus RT. CONCLUSIONS: RT for locally-advanced
      prostate cancer has a higher incidence of mortality, secondary diagnoses and
      interventions, SRE, and ADT utilization compared to RP. This may lead to
      increased costs and have implications for quality of life. Our findings support
      the utility of RP in appropriately selected men with locally-advanced prostate
      cancer given the possible decreased morbidity and survival benefit.

PMID- 30281011
TI  - Ileal perforation in the setting of atezolizumab immunotherapy for advanced
      bladder cancer.
AB  - Atezolizumab is a promising immunotherapy for advanced urothelial carcinoma. Like
      other immune checkpoint inhibitors, it can produce rare immune-related adverse
      events (IRAEs). Here we present the recent case of a patient with metastatic
      bladder cancer who developed diarrhea and abdominal pain months after beginning
      atezolizumab therapy. He presented to our institution with an ileal perforation
      secondary to atezolizumab-induced enterocolitis. After surgical repair, the
      patient's condition improved, and he was discharged. We discuss the management of
      atezolizumab-induced enterocolitis, including the importance of early recognition
      and intervention to prevent more devastating complications.

PMID- 30281012
TI  - Epithelioid angiomyolipoma metastasis to the rectus abdominis.
AB  - A 37-year-old female presented with abdominal pain. An abdominal computed
      tomography scan demonstrated a 10 cm x 13 cm left renal mass. An open adrenal
      sparing radical nephrectomy was performed. The pathological diagnosis was
      epithelioid angiomyolipoma. Five-year surveillance did not demonstrate recurrence
      of disease. However, a 1.8 cm x 2.5 cm mass on the rectus abdominis muscle was
      identified after 5 years. Biopsy of the mass demonstrated histologic findings
      consistent with the primary tumor. Herein, we report a case of metastatic renal
      epithelioid angiomyolipoma to the rectus abdominis muscle more than 5 years after
      resection of primary renal tumor.

PMID- 30281014
TI  - Abstracts of the Mid-Atlantic Section of the American Urological Association
      Annual Meeting October 4 - 7, 2018 Washington, DC.

PMID- 30281013
TI  - Primitive neuroectodermal tumor arising from an untreated congenital undescended
      testicle.
AB  - A 26-year-old male with a personal history of schizophrenia initially presented
      with a 13 cm pelvic mass corresponding to a cryptorchidic testis. The patient was
      treated with primary and second-line chemotherapy for metastatic germ-cell tumor
      followed by surgical consolidation. Final pathology revealed a primitive
      neuroectodermal tumor (PNET) mixed with mature teratoma. Despite
      multidisciplinary management, significant patient non-compliance led to
      inadequate follow up and treatment delays ultimately resulting in death. To our
      knowledge, this is the only reported case of teratoma with malignant
      transformation arising from an untreated congenital undescended testicle.

PMID- 30281015
TI  - Notification that new names of prokaryotes, new combinations, and new taxonomic
      opinions have appeared in volume 68, part 7, of the IJSEM.

PMID- 30281016
TI  - Megasphaera stantonii sp. nov., a butyrate-producing bacterium isolated from the
      cecum of a healthy chicken.
AB  - A novel mesophilic, anaerobic, Gram-stain-negative bacterium was isolated from
      the cecum of a healthy white leghorn chicken, and designated AJH120T. Cells were
      coccoid or diplococcoid with an average size of 0.8-1.8 um and were non-motile
      with no evidence of spores. Phylogenetic analysis of 16S rRNA gene sequences
      revealed this organism to be a member of the genus Megasphaera, with the closest
      relatives being Megasphaera elsdenii (95 % sequence identity) and Megasphaera
      cerevisiae (95 % sequence identity). Growth was observed between 30 and 50 
      degrees C and between pH 5.0 and 9.0. AJH120T utilized a variety of carbon
      sources, including succinate, gluconate, fructose, ribose and pyruvate, as well
      as many individual amino acids. The DNA G+C content for the genome sequence of
      AJH120T was 52.1 mol%. Digital DNA-DNA hybridization (dDDH), average nucleotide
      identity (ANI) and average amino acid identity (AAI) between AJH120T and close
      taxonomic relatives, indicated divergence consistent with the strain representing
      a novel species. The major fatty acid methyl esters of the organism were C12 : 0,
      C14 : 0 3-OH, C18 : 1omega9c, C16 : 0 and C16 : 1omega9c. AJH120T was able to
      produce several short chain fatty acids, including butyrate, acetate, propionate
      and isovalerate. Together, these data indicate that AJH120T represents a novel
      species within the genus Megasphaera. We propose the name Megasphaerastantonii
      sp. nov. for the species. The type strain of this species is AJH120T (=DSM
      106750T=CCUG 71842T).

PMID- 30281017
TI  - Yeast Ded1 promotes 48S translation pre-initiation complex assembly in an mRNA
      specific and eIF4F-dependent manner.
AB  - DEAD-box RNA helicase Ded1 is thought to resolve secondary structures in mRNA 5'
      untranslated regions (5'-UTRs) that impede 48S preinitiation complex (PIC)
      formation at the initiation codon. We reconstituted Ded1 acceleration of 48S PIC
      assembly on native mRNAs in a pure system, and recapitulated increased Ded1
      dependence of mRNAs that are Ded1-hyperdependent in vivo. Stem-loop (SL)
      structures in 5'-UTRs of native and synthetic mRNAs increased the Ded1
      requirement to overcome their intrinsically low rates of 48S PIC recruitment.
      Ded1 acceleration of 48S assembly was greater in the presence of eIF4F, and
      domains mediating one or more Ded1 interactions with eIF4G or helicase eIF4A were
      required for efficient recruitment of all mRNAs; however, the relative importance
      of particular Ded1 and eIF4G domains were distinct for each mRNA. Our results
      account for the Ded1 hyper-dependence of mRNAs with structure-prone 5'-UTRs, and
      implicate an eIF4E.eIF4G.eIF4A.Ded1 complex in accelerating 48S PIC assembly on
      native mRNAs.

PMID- 30281018
TI  - Genetic basis for coordination of meiosis and sexual structure maturation in
      Cryptococcus neoformans.
AB  - In the human fungal pathogen Cryptococcus neoformans, sex can benefit its
      pathogenicity through production of meiospores, which are believed to offer both
      physical and meiosis-created lineage advantages for its infections. Cryptococcus
      sporulation occurs following two parallel events, meiosis and differentiation of
      the basidium, the characteristic sexual structure of the basidiomycetes. However,
      the circuit integrating these events to ensure subsequent sporulation is unclear.
      Here, we show the spatiotemporal coordination of meiosis and basidial maturation
      by visualizing event-specific molecules in developing basidia defined by a
      quantitative approach. Monitoring of gene induction timing together with genetic
      analysis reveals co-regulation of the coordinated events by a shared regulatory
      program. Two RRM family regulators, Csa1 and Csa2, are crucial components that
      bridge meiosis and basidial maturation, further determining sporulation. We
      propose that the regulatory coordination of meiosis and basidial development
      serves as a determinant underlying the production of infectious meiospores in C.
      neoformans.

PMID- 30281019
TI  - Visualization of the type III secretion mediated Salmonella-host cell interface
      using cryo-electron tomography.
AB  - Many important gram-negative bacterial pathogens use highly sophisticated type
      III protein secretion systems (T3SSs) to establish complex host-pathogen
      interactions. Bacterial-host cell contact triggers the activation of the T3SS and
      the subsequent insertion of a translocon pore into the target cell membrane,
      which serves as a conduit for the passage of effector proteins. Therefore the
      initial interaction between T3SS-bearing bacteria and host cells is the critical
      step in the deployment of the protein secretion machine, yet this process remains
      poorly understood. Here, we use high-throughput cryo-electron tomography (cryo
      ET) to visualize the T3SS-mediated Salmonella-host cell interface. Our analysis
      reveals the intact translocon at an unprecedented level of resolution, its
      deployment in the host cell membrane, and the establishment of an intimate
      association between the bacteria and the target cells, which is essential for
      effector translocation. Our studies provide critical data supporting the long
      postulated direct injection model for effector translocation.

PMID- 30281020
TI  - Medial orbitofrontal inactivation does not affect economic choice.
AB  - How are decisions made between different goods? One theory spanning several
      fields of neuroscience proposes that their values are distilled to a single
      common neural currency, the calculation of which allows for rational decisions.
      The orbitofrontal cortex (OFC) is thought to play a critical role in this
      process, based on the presence of neural correlates of economic value in lateral
      OFC in monkeys and medial OFC in humans. We previously inactivated lateral OFC in
      rats without affecting economic choice behavior. Here we inactivated medial OFC
      in the same task, again without effect. Behavior in the same rats was disrupted
      by inactivation during progressive ratio responding previously shown to depend on
      medial OFC, demonstrating the efficacy of the inactivation. These results
      indicate that medial OFC is not necessary for economic choice, bolstering the
      proposal that classic economic choice is likely mediated by multiple, overlapping
      neural circuits.

PMID- 30281021
TI  - Changes in mRNA abundance drive shuttling of RNA binding proteins, linking
      cytoplasmic RNA degradation to transcription.
AB  - Alterations in global mRNA decay broadly impact multiple stages of gene
      expression, although signals that connect these processes are incompletely
      defined. Here, we used tandem mass tag labeling coupled with mass spectrometry to
      reveal that changing the mRNA decay landscape, as frequently occurs during viral
      infection, results in subcellular redistribution of RNA binding proteins (RBPs)
      in human cells. Accelerating Xrn1-dependent mRNA decay through expression of a
      gammaherpesviral endonuclease drove nuclear translocation of many RBPs, including
      poly(A) tail-associated proteins. Conversely, cells lacking Xrn1 exhibited
      changes in the localization or abundance of numerous factors linked to mRNA
      turnover. Using these data, we uncovered a new role for relocalized cytoplasmic
      poly(A) binding protein in repressing recruitment of TATA binding protein and RNA
      polymerase II to promoters. Collectively, our results show that changes in
      cytoplasmic mRNA decay can directly impact protein localization, providing a
      mechanism to connect seemingly distal stages of gene expression.

PMID- 30281022
TI  - Differing isoforms of the cobalamin binding photoreceptor AerR oppositely
      regulate photosystem expression.
AB  - Phototrophic microorganisms adjust photosystem synthesis in response to changes
      in light intensity and wavelength. A variety of different photoreceptors regulate
      this process. Purple photosynthetic bacteria synthesize a novel photoreceptor
      AerR that uses cobalamin (B12) as a blue-light absorbing chromophore to control
      photosystem synthesis. AerR directly interacts with the redox responding
      transcription factor CrtJ, affecting CrtJ's interaction with photosystem
      promoters. In this study, we show that AerR is translated as two isoforms that
      differ by 41 amino acids at the amino terminus. The ratio of these isoforms was
      affected by light and cell growth phase with the long variant predominating
      during photosynthetic exponential growth and the short variant predominating in
      dark conditions and/or stationary phase. Pigmentation and transcriptomic analyses
      show that the short AerR variant represses, while long variant activates,
      photosynthesis genes. The long form of AerR also activates many genes involved in
      cellular metabolism and motility.

PMID- 30281023
TI  - Fusion surface structure, function, and dynamics of gamete fusogen HAP2.
AB  - HAP2 is a class II gamete fusogen in many eukaryotic kingdoms. A crystal
      structure of Chlamydomonas HAP2 shows a trimeric fusion state. Domains D1, D2.1
      and D2.2 line the 3-fold axis; D3 and a stem pack against the outer surface.
      Surprisingly, hydrogen-deuterium exchange shows that surfaces of D1, D2.2 and D3
      closest to the 3-fold axis are more dynamic than exposed surfaces. Three fusion
      helices in the fusion loops of each monomer expose hydrophobic residues at the
      trimer apex that are splayed from the 3-fold axis, leaving a solvent-filled
      cavity between the fusion loops in each monomer. At the base of the two fusion
      loops, Arg185 docks in a carbonyl cage. Comparisons to other structures,
      dynamics, and the greater effect on Chlamydomonas gamete fusion of mutation of
      axis-proximal than axis-distal fusion helices suggest that the apical portion of
      each monomer could tilt toward the 3-fold axis with merger of the fusion helices
      into a common fusion surface.

PMID- 30281025
TI  - Effects of antiretroviral combination therapies F/TAF, E/C/F/TAF and R/F/TAF on
      insulin resistance in healthy volunteers: the TAF-IR Study.
AB  - BACKGROUND: Increased insulin resistance (IR), associated with specific
      antiretroviral drugs or drug classes, is an established risk factor for type 2
      diabetes in HIV patients, ultimately increasing morbidity and mortality. To date,
      data on the risk of IR in tenofovir alafenamide (TAF)-based protocols are
      unavailable. METHODS: This prospective randomized, open-label study evaluated the
      effects of IR on 30 healthy volunteers receiving fixed-dose combinations (FDCs)
      of emtricitabine/tenofovir alafenamide (F/TAF),
      elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or
      rilpivirine/emtricitabine/tenofovir alafenamide (R/F/TAF). IR was measured before
      and after 14-day treatments using the hyperinsulinemic-euglycaemic clamp
      technique (HEGC). Changes in IR in each group were evaluated using the mean
      glucose disposal rate, normalized with body weight (MBW [mg glucose/(min*kg)]).
      RESULTS: A total of 30 subjects underwent randomization: one subject in the F/TAF
      arm withdrew consent after randomization and one in the R/F/TAF arm had to be
      excluded because of technical failure during HEGC, resulting in 28 subjects in
      the per-protocol population (F/TAF, n=9 subjects; E/C/F/TAF, n=10 subjects;
      R/F/TAF n=9 subjects). No significant differences were detected on the baseline
      characteristics. IR did not differ among the groups before treatment. None of the
      studied antiretroviral combinations resulted in a significant change in IR after
      14 days compared with baseline values, as measured by MBW (F/TAF, 11.42 +/-3.04
      mean [+/-sd] versus 11.43 +/-3.23, P=0.49; E/C/F/TAF, 10.04 +/-2.49 versus 10.95
      +/-4.26, P=0.30; R/F/TAF, 11.03 +/-1.96 versus 13.01 +/-4.11, P=0.13).
      CONCLUSIONS: Short-term treatment for F/TAF, E/C/F/TAF or R/F/TAF did not
      increase IR in healthy male volunteers.

PMID- 30281026
TI  - Cystic fibrosis survival: the changing epidemiology.
AB  - PURPOSE OF REVIEW: Tracking patient outcomes using cystic fibrosis (CF) national
      data registries, we have seen a dramatic improvement in patient survival. As
      there are multiple ways to measure survival, it is important for readers to
      understand these different metrics in order to clearly translate this information
      to patients and their families. The aims of this review were to describe measures
      of survival and to review the recent literature pertaining to survival in CF to
      capture the changing epidemiology. RECENT FINDINGS: Although survival has
      improved on a population level, several individual factors continue to impact
      survival such as sex, age of diagnosis, ethnic background and lung function.
      Survival estimates, conditional on surviving to a specified age, are more
      relevant to individuals living with CF today and are higher than the reported
      overall median age of survival. There is some evidence to suggest that newborn
      screening (NBS) has resulted in prolonged survival in CF. SUMMARY: Prognosis in
      CF is often described by reporting the median age of survival, the median age of
      death, the median survival conditional on living to a certain age and the
      survival by birth cohort. Each of these metrics provide useful information
      depending on an individual's personal disease trajectory. The median age of
      survival continues to increase in CF in many countries while mortality rates are
      decreasing. Several factors have been associated with worse survival such as
      female sex, ethnicity, worse nutritional status, lower lung function and
      microbiology. When comparing survival between countries, one needs to ensure that
      similar data collection and processing techniques are used to ensure valid and
      robust comparisons.

PMID- 30281027
TI  - Effectiveness of Cognitive Behavioral Therapy for Depression and Anxiety in
      Patients With Cardiovascular Disease: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: Depression and anxiety are highly prevalent in patients with
      cardiovascular disease (CVD) and influence their mental well-being and CVD
      prognosis. The primary objective was to assess the effectiveness of cognitive
      behavioral therapy (CBT) for depression and anxiety in patients with CVD.
      Secondary objectives were to assess the impact of CBT on cardiovascular
      mortality, cardiovascular events, patient satisfaction, and quality of life.
      METHODS: MEDLINE, PsycINFO, CINAHL, CENTRAL, and alternative sources were
      searched for randomized controlled trials and observational studies with a
      control. Studies were required to assess CBT in coronary heart disease, acute
      coronary syndrome, atrial fibrillation, or postmyocardial infarction patients,
      with anxiety and/or depression. Studies were independently screened by two
      reviewers and critically appraised using the Cochrane Risk of Bias tool. The
      random-effects model was used to pool standardized mean differences (SMD).
      RESULTS: Twelve randomized controlled trials were included. At follow-up,
      depression (SMD = -0.35, 95% confidence interval [CI] = -0.52 to -0.17, p < .001,
      I = 59%) and anxiety (SMD = -0.34, 95% CI = -0.65 to -0.03, p = .03, I = 71%)
      scores were significantly lower in CBT patients compared with controls. Change in
      mental health quality of life (SF-12) was also significantly greater for CBT
      patients, compared with controls (mean difference = 3.62, 95% CI = 0.22 to 7.02,
      p = .04, I = 0%). No differences in patient satisfaction or cardiovascular events
      were evident between CBT and control groups. Among the study reports included in
      this meta-analysis, data specific to cardiovascular mortality were not reported.
      CONCLUSIONS: Cognitive behavioral therapy seems to be an effective treatment for
      reducing depression and anxiety in patients with CVD and should be considered in
      standard clinical care.

PMID- 30281028
TI  - Chronic Family Stress and Adolescent Health: The Moderating Role of Emotion
      Regulation.
AB  - OBJECTIVE: The aim of the study was to assess whether the association between
      chronic family stress and physiological measures is moderated by emotion
      regulation strategies in an adolescent sample. METHODS: Chronic family stress was
      assessed via a semistructured interview and emotion regulation strategies
      (cognitive reappraisal and suppression) via questionnaire among 261 adolescents
      (14.57 (1.07) years). Several metabolic (waist-hip ratio, systolic and diastolic
      blood pressure) and inflammatory markers (basal and stimulated proinflammatory
      cytokine production in response to bacterial challenge) as well as glucocorticoid
      sensitivity were assessed. RESULTS: There were no main effects of chronic family
      stress, cognitive reappraisal, or suppression on physiological measures (all p's
      > .10). Emotion regulation moderated the association between chronic family
      stress and physiological measures. As chronic family stress increased,
      adolescents higher in cognitive reappraisal had smaller waist-hip ratios (B = 
      .003, SE = .001, p = .015) and lower systolic blood pressure (B = -.303, SE =
      .143, p = .035), although no moderation was found with respect to inflammatory
      markers and glucocorticoid sensitivity (all p's > .30). In addition, as chronic
      family stress increased, adolescents higher in suppression showed evidence of
      higher stimulated proinflammatory cytokine production (B = .046, SE = .020, p =
      .021) and lower glucocorticoid sensitivity (B = .051, SE = .021, p = .015),
      although basal inflammation and metabolic measures were not moderated by
      suppression (all p's > .50). CONCLUSIONS: This study suggests that the types of
      emotion regulation strategies used by adolescents may affect the extent to which
      chronic family stress affects important metabolic and immune processes.

PMID- 30281024
TI  - Bid maintains mitochondrial cristae structure and function and protects against
      cardiac disease in an integrative genomics study.
AB  - Bcl-2 family proteins reorganize mitochondrial membranes during apoptosis, to
      form pores and rearrange cristae. In vitro and in vivo analysis integrated with
      human genetics reveals a novel homeostatic mitochondrial function for Bcl-2
      family protein Bid. Loss of full-length Bid results in apoptosis-independent,
      irregular cristae with decreased respiration. Bid-/- mice display stress-induced
      myocardial dysfunction and damage. A gene-based approach applied to a biobank,
      validated in two independent GWAS studies, reveals that decreased genetically
      determined BID expression associates with myocardial infarction (MI)
      susceptibility. Patients in the bottom 5% of the expression distribution exhibit
      >4 fold increased MI risk. Carrier status with nonsynonymous variation in Bid's
      membrane binding domain, BidM148T, associates with MI predisposition.
      Furthermore, Bid but not BidM148T associates with Mcl-1Matrix, previously
      implicated in cristae stability; decreased MCL-1 expression associates with MI.
      Our results identify a role for Bid in homeostatic mitochondrial cristae
      reorganization, that we link to human cardiac disease.

PMID- 30281029
TI  - Ocular myasthenia gravis: an update on diagnosis and treatment.
AB  - PURPOSE OF REVIEW: Myasthenia gravis is an autoimmune disease that commonly
      affects the palpebral and extraocular muscles. Ocular myasthenia gravis (OMG) is
      a variant of the disease that is confined to the ocular muscles but frequently
      becomes generalized over time. The diagnosis of OMG is often challenging but both
      clinical and laboratory findings are helpful in confirming the clinical
      suspicion. This review provides an update on the diagnostic approach and
      therapeutic options for OMG. RECENT FINDINGS: Antimuscle-specific tyrosine kinase
      and LDL-related receptor-related protein 4 are newly available serologic testing
      for myasthenia gravis that can help in increasing the diagnostic sensitivity of
      OMG. They should be included to the diagnostic algorithm of OMG in appropriate
      clinical situations. SUMMARY: OMG remains a primarily clinical diagnosis, but
      recent advances in laboratory testing can improve the diagnostic accuracy and
      should be used in appropriate clinical settings. The mainstay of treatment for
      OMG has not significantly changed over the past years, but the increasing
      availability of steroid-sparing agents improved the disease control while
      minimizing steroid-induced complications.

PMID- 30281030
TI  - Myelin oligodendrocyte glycoprotein-IgG-associated optic neuritis.
AB  - PURPOSE OF REVIEW: Myelin oligodendrocyte glycoprotein (MOG)-IgG-associated optic
      neuritis has been established as a new entity of optic neuropathy. We will review
      recent advances in pathophysiology, diagnosis, and clinical manifestations of MOG
      IgG-associated optic neuritis to better understand its distinctive
      characteristics. RECENT FINDINGS: MOG is expressed on the surface of myelin
      sheaths and oligodendrocytes. MOG is highly immunogenic and is a potential target
      of inflammatory demyelinating disease. MOG-IgG activate immune responses and
      cause demyelination without astrocytopathy. MOG-IgG are measured by cell-based
      assays, which have higher sensitivity and specificity than ELISA. Patients with
      MOG-IgG-associated optic neuritis present with initially severe vision loss, are
      more likely to have optic disc edema, but have favorable visual outcomes.
      Furthermore, patients with MOG-IgG-associated optic neuritis have higher rates of
      recurrence compared with MOG-IgG seronegative patients. MOG-IgG-associated optic
      neuritis responds well to steroid treatment, however, close monitoring for signs
      of relapse and long-term immunosuppression may be necessary. SUMMARY: MOG-IgG
      associated optic neuritis demonstrates distinctive pathophysiological and
      clinical characteristics from optic neuritis in aquaporin4-IgG seropositive or
      multiple sclerosis patients. Measurements of MOG-IgG titers by cell-based assays
      will be helpful for the diagnosis and treatment of optic neuritis.

PMID- 30281031
TI  - Ocular manifestations of cytomegalovirus in immunocompetent hosts.
AB  - PURPOSE OF REVIEW: This review highlights recent studies that have increasingly
      implicated cytomegalovirus (CMV) as a significant cause of keratouveitis and
      retinitis in immunocompetent hosts. RECENT FINDINGS: Molecular testing has
      identified that CMV infection is frequently present in cases of Posner-Schlossman
      and Fuchs, keratouveitis syndromes previously presumed to be idiopathic
      conditions. Ocular hypertension and endothelial cell loss are important
      complications of CMV keratouveitis and are likely mediated by viral invasion of
      the trabecular meshwork and corneal endothelium. Topical ganciclovir is a well
      tolerated, effective, and economical therapy. CMV retinitis is possible in the
      absence of HIV/AIDS. SUMMARY: CMV has long been considered an innocuous infection
      in the general population, though recent studies have found otherwise.
      Intraocular reactivation, replication, and invasion of the trabecular meshwork
      and endothelium lead to recurrent bouts of ocular hypertension and endothelial
      cell loss, the complications of which may be tempered with initiation of
      antivirals. Topical ganciclovir is a promising therapy that needs investigation.
      CMV retinitis, an entity previously believed isolated to the severely
      immunosuppressed population, has been reported on numerous occasions in
      presumably immunocompetent individuals, particularly following local steroid
      injections. Further studies may elucidate the pathogenesis of CMV in
      immunocompetent populations.

PMID- 30281032
TI  - Multimodal imaging of diabetic retinopathy.
AB  - PURPOSE OF REVIEW: Diabetic retinopathy is the most common microvascular
      complication of diabetes mellitus and a leading cause of blindness throughout the
      world. Ocular imaging continues to play a vital role in the diagnosis, management
      and monitoring of diabetic retinopathy. Major technological advancements in
      imaging over the past decade have improved our understanding and knowledge of
      diabetic retinopathy and therefore a multimodal approach to imaging has become
      the standard of care. RECENT FINDINGS: Updates to traditional technologies such
      as digital fundus photography along with recent advancements in optical coherence
      tomography (OCT) and OCT angiography (OCTA) have provided clinicians with new
      information and improved efficiency. SUMMARY: In this review, we describe the
      benefits and clinical applications of several imaging techniques in diabetic
      retinopathy including color photography, fluorescein angiography, OCT, OCTA and
      adaptive optics. Understanding the indications and limitations of each technology
      allows clinicians to gain the most information from each modality and thereby
      optimize patient care.

PMID- 30281033
TI  - Next-generation sequencing-based minimal residual disease monitoring in patients
      receiving allogeneic hematopoietic stem cell transplantation for acute myeloid
      leukemia or myelodysplastic syndrome.
AB  - PURPOSE OF REVIEW: The monitoring of minimal residual disease (MRD) has important
      clinical implications in both the pre and postallogeneic stem cell transplant
      (SCT) setting in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
      Next-generation sequencing (NGS) is a rapidly improving technology whose
      application to the monitoring of MRD is an active area of research. We aim to
      describe existing methods of MRD in AML and MDS, with a focus on the utility of
      NGS in patients undergoing SCT. RECENT FINDINGS: Flow cytometry and quantitative
      PCR have been recommended by the European Leukemia Net as the preferred methods
      of MRD in AML and MDS, but these methods have limitations in cases without a
      disease-defining phenotype and genotype. Clinical trials are currently ongoing to
      assess the use of NGS in the setting of SCT for MDS and AML. Few studies have so
      far assessed the optimal method of MRD monitoring in the posttransplant setting.
      SUMMARY: The optimal method for the monitoring of MRD in AML and MDS both pre and
      post transplant may require more than one technology. NGS holds great promise for
      the monitoring of MRD, with prospective trials currently ongoing to evaluate its
      efficacy in this regard.

PMID- 30281034
TI  - When might transferrin, hemopexin or haptoglobin administration be of benefit
      following the transfusion of red blood cells?
AB  - PURPOSE OF REVIEW: After transfusion, a percentage of red blood cells undergo
      hemolysis within macrophages. Intravascular exposures to hemin and hemoglobin
      (Hb) can occur after storage bag hemolysis, some transfusion reactions, during
      use of medical assist devices and in response to bacterial hemolysins. Proteins
      that regulate iron, hemin and Hb either become saturated after iron excess
      (transferrin, Tf) or depleted after hemin (hemopexin, Hpx) and Hb (haptoglobin,
      Hp) excess. Protein saturation or stoichiometric imbalance created by transfusion
      increases exposure to non-Tf bound iron, hemin and Hb. Tf, Hpx and Hp are being
      developed for hematological disorders where iron, hemin and Hb contribute to
      pathophysiology. However, complexed to their ligands, each represents a potential
      iron source for pathogens, which may complicate the use of these proteins. RECENT
      FINDINGS: Erythrophagocytosis by macrophages and processes of cell death that
      lead to reactive iron exposure are increasingly described. In addition, the
      effects of transfusion introduced circulatory hemin and Hb are described in the
      literature, particularly following large volume transfusion, infection and during
      concomitant medical device use. SUMMARY: Supplementation with Tf, Hpx and Hp
      suggests therapeutic potential in conditions of extravascular/intravascular
      hemolysis. However, their administration following transfusion may require
      careful assessment of concomitant disease.

PMID- 30281035
TI  - To transfuse or not transfuse: an intensive appraisal of red blood cell
      transfusions in the ICU.
AB  - PURPOSE OF REVIEW: This review is a critical appraisal of the current data
      comparing restrictive vs. liberal transfusion strategies for patients who are
      critically ill in ICUs. We focus on four subsets of critically ill patients:
      pediatric patients, patients with gastrointestinal bleeds, septic patients and
      patients undergoing cardiac surgery. RECENT FINDINGS: Almost a decade after the
      TRICC trial, a randomized trial showing the safety of a restrictive transfusion
      threshold in critically ill patients, four large randomized controlled trials
      have shown that a restrictive transfusion strategy is safe in pediatric
      critically ill patients, patients with acute upper gastrointestinal bleeds,
      patients with septic shock and patients undergoing cardiac surgery. A large
      multicenter randomized trial is underway to determine the safety of a restrictive
      strategy in myocardial infarction. SUMMARY: A restrictive transfusion threshold
      is recommended in nearly all critically ill patients. This is at least
      noninferior to more liberal transfusion practice; in addition, a restrictive
      threshold has shown improved outcomes in some patients and decreased chances of
      adverse events in patients. Judicious use of red cells improves patient outcome
      and protects the blood supply, a limited resource. More data are needed to
      determine appropriate transfusion threshold recommendations for patients with
      traumatic brain injury and acute coronary syndrome.

PMID- 30281036
TI  - Restoring antiviral immunity with adoptive transfer of ex-vivo generated T cells.
AB  - PURPOSE OF REVIEW: Latent viruses such as cytomegalovirus (CMV), Epstein-Barr
      virus (EBV) and adenovirus (ADV) often reactivate in immunocompromised patients,
      contributing to poor clinical outcomes. A rapid reconstitution of antiviral
      responses via adoptive transfer of virus-specific T cells (VSTs) can prevent or
      eradicate even refractory infections. Here, we evaluate this strategy and the
      associated methodological, manufacturing and clinical advances. RECENT FINDINGS:
      From the early pioneering but cumbersome efforts to isolate CMV-specific T cell
      clones, new approaches and techniques have been developed to provide quicker,
      safer and broader-aimed ex-vivo antigen-specific cells. New manufacturing
      strategies, such as the use of G-Rex flasks or 'priming' with a library of
      overlapping viral peptides, allow for culturing greater numbers of cells that
      could be patient-specific or stored in cell banks for off-the-shelf applications.
      Rapid isolation of T cells using major histocompatibility complex tetramer or
      cytokine capture approaches, or genetic reprogramming of cells to target viral
      antigens can accelerate the generation of potent cellular products. SUMMARY:
      Advances in the ex-vivo generation of VSTs in academic medical centres and as off
      the-shelf blood bank-based or commercially produced reagents are likely to result
      in broader accessibility and possible manufacturing cost reduction of these cell
      products, and will open new therapeutic prospects for vulnerable and critically
      ill immunocompromised patients.

PMID- 30281037
TI  - Towards increasing shelf life and haemostatic potency of stored platelet
      concentrates.
AB  - PURPOSE OF REVIEW: Platelet transfusion is a widely used therapy in treating or
      preventing bleeding and haemorrhage in patients with thrombocytopenia or trauma.
      Compared with the relative ease of platelet transfusion, current practice for the
      storage of platelets is inefficient, costly and relatively unsafe, with platelets
      stored at room temperature (RT) for upto 5-7 days. RECENT FINDINGS: During
      storage, especially at cold temperatures, platelets undergo progressive and
      deleterious changes, collectively termed the 'platelet storage lesion', which
      decrease their haemostatic function and posttransfusion survival. Recent progress
      in understanding platelet activation and host clearance mechanisms is leading to
      the consideration of both old and novel storage conditions that use refrigeration
      and/or cryopreservation to overcome various storage lesions and significantly
      extend platelet shelf-life with a reduced risk of pathogen contamination.
      SUMMARY: A review of the advantages and disadvantages of alternative methods for
      platelet storage is presented from both a clinical and biological perspective. It
      is anticipated that future platelet preservation involving cold, frozen and/or
      pathogen reduction strategies in a proper platelet additive solution will enable
      longer term and safer platelet storage.

PMID- 30281038
TI  - Impact of air pollution on depression and suicide.
AB  - Air pollution is one of the greatest public health threats worldwide. All
      substances appearing in excessive quantities in the atmosphere, such as
      particulate matter, nitrogen oxides or sulphur oxides may be its ingredients.
      Depending on their size and nature, these compounds may cause greater risk of
      suffering from respiratory or cardiovascular diseases for exposed people as well
      as exacerbation and increased mortality due to these illnesses. Smaller particles
      may penetrate the brain's blood barrier and thus affect the central nervous
      system. In many studies, they have been shown to have negative effects on brain
      structure, like diminishing white matter or neuronal degeneration, leading to the
      earlier onset of Alzheimer or Parkinson disease. Nevertheless, there are reports
      of association of air pollution with mood disorders, depression, and even
      suicide. There are many risk factors for these conditions, most important of
      which are the social situation or chronic diseases. However, it has also been
      confirmed that the environment may affect mental health. This article will
      present experimental, clinical and epidemiological studies on exposure to air
      pollution and its impact on depressive disorders and suicide. Our goal is to
      determine the relationship between air pollution and incidence of depression and
      suicides.

PMID- 30281040
TI  - ?

PMID- 30281039
TI  - [Evaluation of adverse drug reactions associated with direct oral anticoagulants
      recorded in the Italian Pharmacovigilance Network database using a specifically
      developed risk index].
AB  - The introduction into clinical practice of direct oral anticoagulants (DOAC) has
      widened the scenario in the prevention and treatment of thromboembolism. However,
      the evaluation of the balance between the thrombotic and hemorrhagic risks is a
      critical issue in the choice of an oral anticoagulant agent. The availability of
      safety and efficacy data for each drug represents the basis to operate treatment
      choices. As there are no head-to-head studies comparing the different DOACs in
      terms of safety and efficacy, and considering the differences in registrative
      trial designs and characteristics of enrolled populations, several meta-analyses
      and real-life studies have tried to trace the safety and efficacy profiles on
      DOACs, but at present no definitive conclusions can be drawn due to numerous
      existing biases. One possible aid to help clinicians in their treatment choice is
      the evaluation of self-reported adverse drug reactions (ADRs) available in drug
      regulatory agency databases such as the Italian Medicines Agency (AIFA)
      pharmacovigilance database. We conducted a search in the National
      Pharmacovigilance Network database, available on AIFA website, in order to
      retrieve all the ADRs related to oral anticoagulants occurred in the period 2016
      2017. We then calculated an ADR risk index (RI) for each drug, where an RI =1
      indicates a balance between the percentage of ADR share and the percentage of
      market share for each DOAC; and an RI <1 indicates a rate of ADR lower than the
      rate of market share (more safe DOAC). The results showed that rivaroxaban is the
      DOAC with the lowest RI among the four molecules available today in Italy.
      Despite the limitations of this study, we believe that ADR RI can be a valuable
      adjunctive tool to help clinicians in their everyday clinical practice.

PMID- 30281041
TI  - [Which role today for intra-aortic balloon counterpulsation?]
AB  - Intra-aortic balloon pump (IABP) is a percutaneous assist device that is easy to
      implant, is associated with low complication rates and, therefore, is widely
      used. It is commonly applied by femoral access, although it can be used with
      axillary access. It reduces afterload and preload, with a slight increase in mean
      arterial pressure and coronary perfusion. For these characteristics, it has been
      extensively used in cardiogenic shock, even without a clear demonstration of
      efficacy from randomized clinical trials; the IABP-SHOCK II study, the largest
      trial carried out so far, failed to demonstrate the usefulness of IABP in this
      setting. Furthermore, the routine use of IABP in patients with acute anterior
      myocardial infarction was not associated with any benefit in reducing ischemic
      area at cardiac magnetic resonance, as shown by the CRISP-AMI trial. For these
      reasons, the international guidelines do not support the routine use of IABP in
      acute myocardial infarction complicated by cardiogenic shock, suggesting instead
      its use in different scenarios such as heart failure associated with acute
      mechanical complications or acute myocarditis. IABP is currently used in patients
      undergoing percutaneous coronary interventions or surgical coronary
      revascularization judged at high risk of complications. In the former scenario,
      the evidence from the literature is very scarce; in the latter one, small trials
      and meta-analytical studies suggest a treatment benefit with IABP in the
      preoperative period.Despite limited evidence of efficacy, IABP will continue to
      play an important role in today's cardiology and is going to remain the most
      widely used mechanical circulatory support device.

PMID- 30281042
TI  - [Prevention of cardioembolic events after intracranial hemorrhage].
AB  - In high thromboembolic risk patients who experienced hemorrhagic stroke, the
      prevention of cardioembolic events and recurrence of intracranial bleeding should
      be guaranteed. The consultant cardiologist should carefully identify the most
      appropriate therapeutic approach for these patients. Among patients with previous
      hemorrhagic stroke, only few restart oral anticoagulant therapy (OAT) after
      cerebral bleeding; however, as reported by some registries, it is likely that
      resuming OAT exerts a favorable effect on the combined outcome of ischemic
      stroke/systemic embolism/all-cause death. In these patients, several parameters
      should be evaluated, such as the type of intracranial bleeding, the presence of a
      previous thromboembolic event, the global thromboembolic risk, as well as the
      history of a previous OAT. This review deals with a particularly interesting
      matter, requiring a number of decision-making turning points, i.e. whether it is
      appropriate or not to start or resume OAT, what drug class and timing choice in
      such a case, and the potential valuable alternatives to OAT.

PMID- 30281043
TI  - [Antithrombotic therapy in patients with atrial fibrillation and acute coronary
      syndrome].
AB  - Antithrombotic therapy in patients with atrial fibrillation and acute coronary
      syndrome is a difficult challenge because of the need of taking into
      consideration three different issues: the cardiac ischemic risk related to
      coronary artery disease and its treatment with angioplasty and stenting; the
      thromboembolic risk associated with atrial fibrillation; and the hemorrhagic risk
      related to the combined use of antiplatelet therapy (with one or two agents) and
      oral anticoagulant therapy.Data from many trials and meta-analyses currently
      support a combination therapy with oral anticoagulants (vitamin K antagonists or
      direct oral anticoagulants) and antiplatelet agents (aspirin and clopidogrel in
      dual or single antiplatelet therapy).Recently completed and ongoing trials aim to
      tackle the still controversial issues of this therapy: the choice of the
      anticoagulant agent and its dosage; the choice of the antiplatelet agent; the use
      of single or dual antiplatelet therapy and its duration.

PMID- 30281044
TI  - [Percutaneous closure of a very large atrial septal defect: a case report and
      literature review].
AB  - Percutaneous transcatheter closure of ostium secundum atrial septal defects (ASD)
      is the gold-standard treatment, because of a comparable efficacy and less
      complications than heart surgery. Nevertheless, percutaneous treatment of very
      large ASD is still considered a challenging procedure and is discouraged for
      diameters larger than 38 mm, especially when atrial septal rims are absent. These
      patients are characterized by more frequent complications when a percutaneous
      approach is attempted. Hence, the treatment of choice is still debated. We report
      the case of a 75-year-old Caucasian male, admitted for congestive heart failure
      secondary to a very large ASD. After accurate sizing with transesophageal
      echocardiography and sizing balloon, percutaneous closure with an Amplatzer
      Septal Occluder was successfully performed, using few simple tricks.

PMID- 30281045
TI  - [ANMCO position paper on sacubitril/valsartan in the management of patients with
      heart failure].
AB  - Sacubitril/valsartan, the first-in-class angiotensin receptor neprilysin
      inhibitor (ARNI), is the first medication to demonstrate a mortality benefit in
      patients with chronic heart failure and reduced ejection fraction (HFrEF) since
      the early 2000s. Sacubitril/valsartan simultaneously suppresses renin-angiotensin
      aldosterone system activation through blockade of angiotensin II type 1 receptors
      and enhances the activity of vasoactive peptides including natriuretic peptides,
      through inhibition of neprilysin, the enzyme responsible for their degradation.
      In the landmark PARADIGM-HF trial, patients with HFrEF treated with
      sacubitril/valsartan had a 20% reduction in the primary composite endpoint of
      cardiovascular death or heart failure hospitalization, a 20% lower risk of
      cardiovascular death, a 21% to 20% lower risk of a first heart failure
      hospitalization, and a 16% to 20% lower risk of death from any cause, compared
      with subjects allocated to enalapril (all p<0.001).Following the trial, new
      international guidelines endorsed sacubitril/valsartan as a class I
      recommendation for the management of patients with HFrEF who remain symptomatic
      despite optimal medical management. In Italy, sacubitril/valsartan is reimbursed
      by the National Health Service since March 2017 within criteria set by the
      Italian Medicines Agency subject to patient inclusion in a dedicated monitoring
      registry. Although numerous post-hoc analyses of the original trial suggested
      that the benefits of this innovative medication may extend across a variety of
      subgroups, many questions do not yet have an evidence-based answer.In this
      position paper, we discuss the current role of sacubitril/valsartan in the
      management of chronic HFrEF, treatment eligibility and the modulating role of
      patients' characteristics. Moreover, we address concerns elicited by the PARADIGM
      HF study and shortcomings of this novel drug, to clarify the place of this new
      therapy in the context of global care of heart failure in Italy. Our aim is to
      provide clinical cardiologists with a concise and practical guidance on when and
      how to use sacubitril/valsartan, to assist clinicians in closing the gap between
      scientific innovation and real-world experience.

PMID- 30281046
TI  - [Appropriateness criteria for the management of anticoagulant therapy in complex
      patients with atrial fibrillation. The opinion of a group of expert Italian
      cardiologists].
AB  - Atrial fibrillation (AF) is a common arrhythmia often associated with high
      thromboembolic risk. The purpose of this position paper is to provide clinicians
      with recommendations useful in managing some important issues regarding the use
      of anticoagulant therapy in patients with AF in particularly complex clinical
      situations.The RAND/UCLA appropriateness method, validated to combine the best
      available scientific evidence with the collective judgment of experts, was used
      to assess the judgment of an expert panel of cardiologists. To this purpose, the
      benefit-to-harm ratio of 37 clinical scenarios was rated. Each indication was
      classified as "appropriate", "uncertain", or "inappropriate" in accordance with
      the panelists' median score.The present document reports the results of this
      consensus process, which led to the development of recommendations for clinical
      practice on how to use anticoagulant therapy in patients with AF in complex
      clinical settings, including the presence of comorbidities, cardioversion, or
      ablation. Non-vitamin K oral anticoagulants are a valid alternative to vitamin K
      antagonists in preventing embolic events in patients with non-valvular AF,
      particularly in case of clinical complexity.

PMID- 30281047
TI  - Polymeric hole-transport materials with side-chain redox-active groups for
      perovskite solar cells with good reproducibility.
AB  - Two monomers, M:OO and M:ON, and their corresponding polymers, P:OO and P:ON,
      were prepared from styrene derivatives N,N-diphenyl-4-vinyl-aniline with
      different substituents (-OCH3 and -N(CH3)2) in the N-phenyl para positions. The
      polymers were synthesised and fully characterised to study their function as hole
      transport materials (HTMs) in perovskite solar cells (PSCs). The thermal, optical
      and electrochemical properties and performance of these monomers and polymers as
      HTMs in PSCs were compared in terms of their structure. The polymers form more
      stable amorphous glassy states and showed higher thermal stability than the
      monomers. The different substituent in the para position influenced the highest
      occupied molecular orbital (HOMO) level, altering the oxidation potential. Both
      monomers and polymers were employed as HTMs in perovskite solar cells with a
      device configuration FTO/bl-TiO2/mp-TiO2/CH3NH3PbI3/HTM/Au resulting in power
      conversion efficiencies of 7.48% for M:OO, 5.14% for P:OO, 5.28% for P:ON and
      3.52% for M:ON. Although showing comparatively low efficiencies, the polymers
      showed much superior reproducibility in comparison with Spiro-OMeTAD or the
      monomers, suggesting further optimisation of polymeric HTMs with redox side
      groups is warranted.

PMID- 30281048
TI  - Phosphatidylcholine in the groove of endothelial cell protein C receptor (EPCR)
      regulates EPCR conformation and protein C recognition.
AB  - Endothelial cell protein C receptor (EPCR), the cellular receptor for protein C
      (PC), facilitates PC activation through the thrombin/thrombomodulin complex and
      regulates thrombin generation. Under pathophysiological conditions like sepsis,
      the interactions between EPCR and PC become impaired. Previous studies have
      demonstrated that the EPCR contains a phospholipid in the antigen-binding groove
      that is responsible for the structural stability of the EPCR and for PC
      recognition. However, an understanding at the atomic level during ligand
      recognition is not fully developed. Molecular dynamics simulations along with
      potential of mean force (PMF) calculations were carried out in order to provide
      molecular insight into the dynamics and free energies of EPCR-PC in the
      absence/presence of phospholipid, namely lysophosphatidylcholine (lysoPCh) and
      phosphatidylcholine (PCh) in the antigen-binding groove of the EPCR. Our data
      reveal that the presence of lipid maintains the optimal conformation of the EPCR
      for PC binding. PMF data further suggest that the PCh system is the most stable
      in comparison with the other systems (lysoPCh and no lipid). With regards to the
      two hydrophobic tails of PCh, one lipid tail regulates EPCR conformation while
      the other promotes ligand recognition by interacting with the keel residue (Phe
      4) of PC. Due to the lack of one hydrophobic tail for the lysoPCh system, the
      EPCR conformation is retained but the affinity of the EPCR towards the ligand
      (PC) is reduced. Our studies for the first time explore the possible mode of
      ligand recognition by the EPCR via the involvement of phosphatidylcholine within
      its hydrophobic groove. The present work provides insight into PCh-dependent
      ligand recognition and hence regulation of the protein C/EPCR complex formation.

PMID- 30281059
TI  - Molecular characterization of Indian pathotypes of Puccinia striiformis f. sp.
      tritici and multigene phylogenetic analysis to establish inter- and intraspecific
      relationships.
AB  - Stripe rust caused by Puccinia striiformis f. sp. tritici (Pst) is one of the
      most devastating diseases of wheat (Triticum spp.) worldwide. Indian isolates
      were characterised based on their phenotypic reaction on differential hosts
      carrying different Yr genes. Based on virulence/avirulence structure, isolates
      were characterised into ten different pathotypes viz. 70S0-2, 67S64, 70S4, 66S0,
      70S64, 66S64-1, 38S102, 47S102, 46S119, and 78S84. These Indian pathotypes of P.
      striiformis f. sp. tritici and 38 pathotypes of other rust species (P. graminis
      tritici and P. triticina) were used in this study to analyze their molecular
      phylogenetic relationship. The nucleotides of rDNA-ITS, partial beta-tubulin and
      ketopantoate reductase genes of all the pathotypes were sequenced directly after
      PCR. Based on sequence data of rDNA-ITS and beta-tubulin, three phylogenetic
      groups corresponding to three different species of Puccinia were obtained. Asian
      isolates formed a distinct evolutionary lineage than from those derived from USA.
      The sequence similarity of Indian pathotypes with other Asian (China and Iran)
      isolates indicated the same origin of pathotypes. The results will allow rapid
      identification of Indian P.striiformis f. sp. tritici pathotypes causing stripe
      rust in wheat, assist in making predictions regarding potential rust pathotypes,
      and identifying sources of resistance to the disease in advance.

PMID- 30281060
TI  - Translumbar hemodialysis long-term catheters: an alternative for vascular access
      failure.
AB  - INTRODUCTION: Vascular access (VA) in hemodialysis (HD) is essential to end-stage
      renal disease (ESRD) patients survival. Unfortunately, after some years in HD
      program, a significant number of patients may develop VA failure for many
      reasons. In this situation, arterial venous fistula (AVF) confection or catheters
      placement in traditional vascular sites (jugular, femoral or subclavian) are not
      feasible. In this scenario, translumbar tunneled dialysis catheter (TLDC) may be
      a salvage option. OBJECTIVES: To describe placement technic, complications, and
      patency of 12 TLDC. METHODS: A retrospective study was performed to analyze 12
      TLDC placement in an angiography suite using fluoroscopic guidance at the
      University Hospital of the Rio Grande do Norte Federal University from January
      2016 to October 2017. The data collected of the total procedures performed
      consisted of demographic characteristics, success rates, observed complications,
      patient survival, and catheter patency. RESULTS: All 12 TLDC were placed with
      success; there were only 2 significant periprocedure complications (major
      bleeding and extubation failure); 41.6% of patients presented a catheter-related
      first infection after 98 +/- 72.1 (6-201) days, but catheter withdrawal was not
      necessary, mean total access patency was 315.5 (range 65 - 631) catheter-days,
      and catheter patency at 3, 6 and 12 months was 91 %, 75%, and 45%. CONCLUSION:
      TLDC is an option for patients with VA failure, improving survival and acting as
      a bridge for renal transplantation.

PMID- 30281061
TI  - Successful multiple-exchange peritoneal dialysis in a patient with severe
      hematological toxicity by methotrexate: case report and literature review.
AB  - Methotrexate is an effective medication to control several diseases; however, it
      can be very toxic, being myelosuppression one of its main adverse effects, which
      increases in severity and frequency in patients with renal failure. We present
      the case of a 68-year-old man with chronic, end-stage renal disease associated
      with ANCA vasculitis, under treatment with peritoneal dialysis, who received the
      medication at a low dose, indicated by disease activity, which presented as a
      complication with severe pancytopenia with mucositis that improved with support
      measures and multiple-exchange peritoneal dialysis. We reviewed 20 cases
      published to date of pancytopenia associated with methotrexate in patients on
      dialysis and found high morbidity and mortality, which is why its use in this
      type of patient is not recommended. However, when this complication occurs, a
      therapeutic option could be the use of multiple-exchange peritoneal dialysis in
      addition to supportive therapy for drug-related toxicity, although it is
      recognized that studies are required to show the role of multiple-exchange
      peritoneal dialysis in the removal of this medication.

PMID- 30281062
TI  - Pathophysiological aspects of nephropathy caused by non-steroidal anti
      inflammatory drugs.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used medications
      associated with nephrotoxicity, especially when used chronically. Factors such as
      advanced age and comorbidities, which in themselves already lead to a decrease in
      glomerular filtration rate, increase the risk of NSAID-related nephrotoxicity.
      The main mechanism of NSAID action is cyclooxygenase (COX) enzyme inhibition,
      interfering on arachidonic acid conversion into E2 prostaglandins E2,
      prostacyclins and thromboxanes. Within the kidneys, prostaglandins act as
      vasodilators, increasing renal perfusion. This vasodilatation is a counter
      regulation of mechanisms, such as the renin-angiotensin-aldosterone system works
      and that of the sympathetic nervous system, culminating with compensation to
      ensure adequate flow to the organ. NSAIDs inhibit this mechanism and can lead to
      acute kidney injury (AKI). High doses of NSAIDs have been implicated as causes of
      AKI, especially in the elderly. The main form of AKI by NSAIDs is hemodynamically
      mediated. The second form of NSAID-induced AKI is acute interstitial nephritis,
      which may manifest as nephrotic proteinuria. Long-term NSAID use can lead to
      chronic kidney disease (CKD). In patients without renal diseases, young and
      without comorbidities, NSAIDs are not greatly harmful. However, because of its
      dose-dependent effect, caution should be exercised in chronic use, since it
      increases the risk of developing nephrotoxicity.

PMID- 30281063
TI  - Reversible posterior encephalopathy syndrome in a 10-year-old child.
AB  - INTRODUCTION: The posterior reversible encephalopathy (PRES) syndrome encompasses
      a set of clinical-radiological findings associated with severe systemic arterial
      hypertension. This case report proposes to discuss the identification, diagnosis,
      and management of PRES in the pediatric population. CASE PRESENTATION: Female
      patient, 10 years old, admitted to the emergency room with complaint of oliguria
      and generalized edema. At the initial physical exam, the only alteration present
      was anasarca. The diagnostic investigation revealed nephrotic syndrome, and
      clinical treatment was started. She evolved on the 8th day of hospitalization
      with peak hypertension, sudden visual loss, reduced level of consciousness,
      nystagmus, and focal seizures requiring intubation. She was transferred to the
      Intensive Care Unit, with neurological improvement, after the established
      therapy. CT scan revealed a discrete hypodense area in the white matter of the
      occipital lobe and anteroposterior groove asymmetry, compatible with PRES.
      DISCUSSION: PRES is due to vasogenic cerebral edema of acute or subacute
      installation. Symptoms include headache and altered consciousness, stupor, coma,
      neurological deficits, seizures and cortical blindness. Nephropathies are the
      main cause of PRES in pediatrics. Magnetic resonance imaging with diffusion of
      molecules is the gold standard for diagnosis. The initial treatment objectives
      are the reduction of blood pressure, antiepileptic therapy, correction of
      hydroelectrolytic and acid-base disorders and management of intracranial
      hypertension. CONCLUSION: PRES is associated with acute hypertension. Early
      diagnosis and proper management may determine a better prognosis and minimize the
      severity of the clinical course.

PMID- 30281064
TI  - Thumb adductor muscle thickness used in the nutritional assessment of chronic
      kidney disease patients under conservative treatment.
AB  - INTRODUCTION: Evaluate the association between the thumb adductor muscle
      thickness and the patient's nutritional status, and propose cutoff points for
      muscle mass depletion in elderly patients with chronic kidney disease (CKD) under
      conservative treatment. Epidemiological and cross-sectional study, including
      patients with CKD stages 3 to 5, older than 60 years. Socioeconomic, clinical,
      physical activity and anthropometric data was obtained. TAMT was described and
      compared according to CKD stage, socioeconomic data, physical activity,
      nutritional status and correlated with age, glomerular filtration rate and
      anthropometric variables. Receiver Operating Characteristic (ROC) curves were
      produced, considering the lean tissue index classification as reference. The cut
      off point was defined by the Youden index. RESULTS: We evaluated 137 individuals.
      The TAMT was lower in malnourished and/or depleted muscle mass individuals; among
      males it was higher among those who practiced physical activities (p <0.05). This
      measure was moderately correlated with BMI, calf and brachial circumferences,
      lean body tissue, lean tissue index and body cell mass (r <0.7); negatively with
      age (r = -0.34). The ROC curve analysis determined cut points of 15.33 mm for
      females and 20.33 mm for males, with 72.22% and 62.50% accuracy, respectively.
      CONCLUSION: TAMT is used to estimate muscle mass and we suggest the cutoff point
      is useful to rule out the likelihood of muscle mass depletion. It is recommended
      that it be used in a complementary way in nutritional assessment.

PMID- 30281065
TI  - IgA nephropathy in Salvador, Brazil: a more aggressive disease?

PMID- 30281066
TI  - A Phase II Randomized, Control Trial of Group B Streptococcus (GBS) Type III
      Capsular Polysaccharide -Tetanus Toxoid (GBS III-TT) Vaccine to Prevent Vaginal
      Colonization with GBS III.
AB  - Background: Group B Streptococcus (GBS) frequently colonizes pregnant women and
      can cause sepsis and meningitis in young infants. If colonization was prevented
      through maternal immunization, a reduction in perinatal GBS disease might be
      possible. A GBS type III capsular polysaccharide (CPS)-tetanus toxoid conjugate
      (III-TT) vaccine was evaluated for safety and efficacy in preventing acquisition
      of GBS colonization. Methods: Healthy, age 18-40 years, non-pregnant women,
      screened to be GBS III vaginal and rectal culture negative, were randomized to
      receive III-TT conjugate or tetanus diphtheria toxoid (Td) vaccine in a
      multicenter, observer blinded trial. GBS vaginal and rectal cultures and blood
      were obtained bimonthly over 18 months. Serum concentrations of GBS III CPS
      specific antibodies were determined by ELISA. Results: Among 1525 women screened
      650 were eligible for the intent to treat analysis. For time to first acquisition
      of vaginal GBS III, vaccine efficacy was 36% (95% CI 1-58%, P = .044) and for
      first rectal acquisition it was this was 43% (95% CI 11-63%, P =.014). Geometric
      mean concentrations of serum GBS type III CPS-specific IgG, 2 months post
      immunization were 12.6 ug/ml (95% CI 9.95-15.81) in GBS III-TT recipients
      representing a 4-fold increase from baseline in 95% of women which persisted.
      Both vaccines were well tolerated. Conclusion: GBS CPS III-TT conjugate vaccine
      significantly delayed acquisition of vaginal and rectal GBS III colonization.
      Besides its use for maternal immunization to passively protect infants with
      maternally-derived antibodies, a multivalent vaccine might also serve to reduce
      fetal and neonatal exposure to GBS.

PMID- 30281067
TI  - Catheter-related bloodstream infections in home parenteral nutrition patients and
      catheter salvage.

PMID- 30281068
TI  - Malocclusion Can Give Additional Hints for Diagnosis of Fetal Alcohol Spectrum
      Disorder.
AB  - Aims: Fetal alcohol spectrum disorder (FASD) is a developmental disorder caused
      by maternal alcohol intake (prevalence: 0.77%). Malocclusion has been described
      in case reports of patients with FASD, but reliable evidence for associations
      between FASD and malocclusion is not documented. Malocclusion is defined as tooth
      irregularity (prevalence: 14.6%) or incorrect relationship between the jaws such
      as lateral crossbites (prevalence: 3.1%). The purpose of this study was to
      investigate possible associations between malocclusion and FASD. Short summary:
      FASD prevalence is high and diagnosis is very difficult; Malocclusions can give
      additional hints for FASD diagnosis; Patients with FASD show growth deficits
      concerning the maxilla; Early and consistent orthodontic supervision and therapy
      can prevent facial asymmetries in FASD patients. Methods: Thirty patients with
      FASD and 30 patients of a healthy control group were examined. Inclusion criteria
      were mixed dentition, verified FASD/absence of FASD (control group), exclusion
      criteria were orthodontic treatment and disorders other than FASD. The extent and
      type of malocclusion were quantified with the peer assessment rating (PAR) index
      based on an analysis of orthodontic plaster models. In addition, anthropometric
      data such as gestational age, body weight and height at birth as well as present
      body weight, height and head circumference at examination date were assessed.
      Results: The PAR index showed a significant increase in malocclusions in FASD
      patients compared to the group that were not diagnosed with FASD (P = 0.002).
      FASD patients showed particular differences in the upper transversal dimension
      with a higher prevalence of crossbites (P = 0.018) and a lower head circumference
      (P < 0.001). Body weight (P < 0.001) and height (P < 0.001) were significantly
      lower for FASD patients at time of birth, but not at the present examination date
      (weight: P = 0.329; height: P = 0.496). When relating weight and height measures
      to age using percentile curves of physiological growth, clinically relevant
      discrepancies could be found for FASD patients. Conclusions: Our results show
      that malocclusion can provide additional evidence for FASD diagnosis. When FASD
      is diagnosed in a child, early referral to an orthodontist is advisable to
      stimulate maxillary growth and consequently prevent further malocclusions.

PMID- 30281069
TI  - Invasive pneumococcal disease in UK children under 1 year of age in the post
      PCV13 era: what are the risks now?
AB  - Background: Invasive pneumococcal disease (IPD) has declined significantly since
      the introduction of pneumococcal conjugate vaccines (PCV). It is not known
      whether certain infant populations remain at higher risk of IPD in countries with
      established PCV13 programmes. We aimed to describe the epidemiology, clinical
      characteristics, serotype distribution and outcomes of IPD in infants, and to
      estimate the relative risk of PCV13-type, non-PCV13 type and overall IPD in
      premature infants compared to term infants during a four-year period after the
      PCV13 programme was established. Methods: Prospective, enhanced national
      surveillance of laboratory-confirmed IPD in England in infants aged <1 year
      diagnosed during 2013-16. Results: There were 517 cases of IPD (incidence:
      19/100,000 infants). Incidence was significantly higher in premature infants
      compared with those born at term (49/100,000 vs 17/100,000; incidence rate ratio
      (IRR) 2.87; p<0.001) with infants born below 28 weeks gestation having the
      highest incidence (150/100,000; IRR 8.8; p<0.001). Of the 454 IPD cases with
      serotyped isolates, most were caused by non-PCV13 serotypes (369 cases, 71.4%),
      with 85 cases (16.4%) due to PCV13 serotypes. There were 31 deaths (case fatality
      rate 6.2%; 95% CI, 4.3-8.6%). Premature infants did not have a higher CFR than
      term infants (p=0.62). Conclusion & relevance: IPD incidence in infants remains
      lower than rates reported prior to PCV7 introduction in England. The risk of IPD
      remains significantly higher in premature infants compared to infants born at
      term, for both PCV13 and non-PCV13 serotypes. Any changes to the infant PCV13
      immunisation schedule may disproportionally affect premature infants.

PMID- 30281070
TI  - Infants at risk for Invasive Pneumococcal Disease in the PCV13 Era.

PMID- 30281071
TI  - New avenues for antimicrobial stewardship: the case for penicillin skin testing
      by pharmacists.
AB  - It is well-appreciated that patients with documented penicillin allergies often
      receive broader-spectrum antibiotics. This practice has been associated with
      increased antimicrobial resistance and cost. In recent years, considerable
      efforts have been made to spread awareness on the implications of self-reported
      penicillin allergies. The use of penicillin skin testing to evaluate for true
      allergies has been strongly recommended by major organizations for decades.
      However, testing remains underutilized. Current literature has suggested various
      models incorporating penicillin allergy screening and testing by different health
      care practitioners (i.e., physicians, allergists, nurses, pharmacists). We
      suggest broader adoption for the role of pharmacists in provision of penicillin
      skin testing. This would help expand the service and maximize the potential
      benefits of penicillin skin testing.

PMID- 30281073
TI  - Randomised study demonstrates sustained benefits of a pre-school intervention
      designed to improve nutrition and physical activity practices.
AB  - Background: Health-promoting programmes must demonstrate sustained efficacy in
      order to make a true impact on public health. This study aimed to determine the
      effect of the Healthy Incentive for Pre-schools project on health-promoting
      practices in full-day-care pre-schools 18 months after a training intervention.
      Methods: Thirty-seven pre-schools completed the initial study and were included
      in this follow-up study. The intervention consisted of one training session with
      either the pre-school 'manager-only' or 'manager and staff' using a specifically
      developed needs-based training resource pack comprised of written educational
      material and a validated health-promoting practice evaluation tool. Direct
      observation data of health-promoting practices were collected and allocated a
      score using the evaluation tool by a research dietitian at three time points; pre
      intervention, between 6 and 9 months post-intervention and at 18-month follow-up.
      An award system was used to incentivise pre-schools to improve their scores.
      Results: Health-promoting practice scores improved significantly (P < 0.001) from
      the 6-9 month post-intervention to the 18-month follow-up evaluation. No
      significant differences were observed between 'manager-only' and 'manager and
      staff' trained pre-schools. Conclusions: The introduction of a pre-school
      evaluation tool supported by a training resource was successfully used to
      incentivise pre-schools to sustain and improve health-promoting practices 18
      months after intervention training.

PMID- 30281072
TI  - Preoperative oral antibiotic prophylaxis reduces surgical site infections after
      elective colorectal surgery: results from a before-after study.
AB  - Background: Surgical site infections (SSI) are common complications after
      colorectal procedures and remain an important source of morbidity and costs.
      Preoperative oral antibiotic prophylaxis is a potential infection control
      strategy, but its effectiveness without simultaneous use of mechanical bowel
      preparation (MBP) is unclear. In this study, we aimed to determine whether
      preoperative oral antibiotics reduce the risk of deep SSI in elective colorectal
      surgery. Methods: We performed a before-after analysis in a teaching hospital in
      the Netherlands. Patients who underwent surgery between January 2012 and December
      2015 were included. On January 1 st, 2013, oral antibiotic prophylaxis with
      tobramycin and colistin was implemented as standard of care prior to colorectal
      surgery. The year before implementation was used as control period. The primary
      outcome was a composite of deep surgical site infection and/or mortality within
      30 days after surgery. Results: Of the 1,410 patients, 352 underwent colorectal
      surgery in the control period and 1,058 in the period after implementation of the
      antibiotic prophylaxis. We observed a decrease in incidence of the primary
      endpoint of 6.2% after prophylaxis implementation. When adjusted for confounders,
      the risk ratio for development of the primary outcome was 0.58 (95% CI 0.40 -
      0.79). Other findings included a decreased risk of anastomotic leakage and a
      reduction of the length of postoperative stay. Conclusions: reoperative oral
      antibiotic prophylaxis prior to colorectal surgery is associated with a
      significant decrease in SSI and/or mortality in a setting without MBP.
      Preoperative oral antibiotics can therefore be considered without MBP for
      patients undergoing colorectal surgery.

PMID- 30281074
TI  - Locking hemodialysis catheters with Trimethoprim-Ethanol-Ca-EDTA to prevent
      bloodstream infections. A randomized, evaluator blinded clinical trial.
AB  - Background: Central line associated bloodstream infections(CLABSI) often result
      from intraluminal microbial colonization and are associated with morbidity,
      mortality, and substantial costs. The use of antimicrobial catheter lock
      solutions may reduce the incidence of CLABSI. Methods: Patients undergoing
      hemodialysis through a prevalent central venous catheter(CVC) were randomly
      assigned to have their CVC locked between dialysis sessions with an antimicrobial
      catheter lock solution containing trimethoprim 5 mg/mL, Ethanol 25% and Ca-EDTA
      3%(Investigational Medical Device, IMD) or heparin 5,000 U/mL(Active Control
      Heparin, ACH). Exit site care was standardized by protocol-driven use of skin
      antiseptics and occlusive dressings. The composite primary endpoint consisted of
      the incidence of CLABSI and the use of intra-catheter thrombolytic treatment(TT).
      Given the viscosity and odor of the IMD, blinding was impossible. Therefore, the
      incidence of CLABSI was adjudicated by a blinded endpoint committee. Results: 270
      patients on hemodialysis were enrolled and followed for a total of 43,738 CVC
      days. Despite the low CLABSI incidence of 0.41/1,000 CVC days in patients
      randomized to ACH, the IMD further reduced the incidence 4.56-fold to 0.09/1,000
      CVC days(P<0.03). The product was well tolerated, and the frequency and severity
      of adverse events were comparable between groups. Intracatheter instillation of
      thrombolytics was more frequent in patients receiving the IMD (12% ACH, 40%
      IMD;P<0.001) but rates of catheter removal did not differ(13% in ACH and 11% in
      IMD). Overall dialysis adequacy was comparable between groups. Conclusions: In
      patients on chronic hemodialysis, a trimethoprim, ethanol and Ca-EDTA Lock
      solution significantly reduced the incidence of CLABSI.

PMID- 30281075
TI  - Does military veteran status and deployment history impact officer involved
      shootings? A case-control study.
AB  - Background: Despite veterans' preference hiring policies by law enforcement
      agencies, no studies have examined the nature or effects of military service or
      deployments on health outcomes. This study will examine the effect of military
      veteran status and deployment history on law enforcement officer (LEO)-involved
      shootings. Methods: Ten years of data were extracted from Dallas Police
      Department records. LEOs who were involved in a shooting in the past 10 years
      were frequency matched on sex to LEOs never involved in a shooting. Military
      discharge records were examined to quantify veteran status and deployment(s).
      Multivariable logistic regression was used to estimate the effect of veteran
      status and deployment history on officer-involved shooting involvement. Results:
      Records were abstracted for 516 officers. In the adjusted models, veteran LEOs
      who were not deployed were significantly more likely to be involved in a shooting
      than non-veteran officers. Veterans with a deployment history were 2.9 times more
      likely to be in a shooting than non-veteran officers. Conclusions: Military
      veteran status, regardless of deployment history, is associated with increased
      odds of shootings among LEOs. Future studies should identify mechanisms that
      explain this relationship, and whether officers who experienced firsthand combat
      exposure experience greater odds of shooting involvement.

PMID- 30281076
TI  - Additional Exertion, Unsupported Assertions, and Hyperhydration Confound
      Rhabdomyolysis Case Study.

PMID- 30281077
TI  - Failure after two-stage exchange arthroplasty for treatment of periprosthetic
      joint infection: the role of antibiotics in the cement spacer.
AB  - Introduction: Failure after a two-stage exchange surgery for periprosthetic joint
      infections (PJI) is high. Previous studies demonstrated that positive cultures at
      reimplantation are associated with failure afterwards. The aim of this
      multicenter study was to define the role of antibiotics in the cement spacer in
      relation to reimplantation cultures and subsequent failure. Methods: We
      retrospectively evaluated two-stage exchange procedures between 2000 and 2015.
      Culture-negative PJIs, cases in whom no cultures were obtained during
      reimplantation and cases without data on cement spacers were excluded. Results:
      344 cases were included. The rate of positive cultures during reimplantation was
      9.5% for cement spacers containing a glycopeptide (27/284) (with or without an
      aminoglycoside) versus 21.7% for those containing monotherapy with an
      aminoglycoside (13/60) (p 0.008), and was mostly attributed by a reduction in
      coagulase-negative staphylococci (CoNS) (17% versus 2%, p < 0.001). Failure rate
      was more than two-folds higher at 40.0% (16/40) in cases with positive cultures
      at reimplantation compared to 15.8% (48/304) for those with negative cultures (p
      < 0.001). Overall, a glycopeptide in the cement spacer was not associated with a
      lower failure rate (18% versus 23%, p 0.3), but was associated with lower failure
      due to CoNS (2.5% versus 13.3%, p < 0.001). Conclusion: In a two-stage exchange
      procedure for PJI, adding a glycopeptide to the cement spacer reduces the rate of
      positive cultures during reimplantation and is associated with a lower failure
      rate due to CoNS afterwards.

PMID- 30281078
TI  - Epidemiological scenario of anisakidosis in Spain based on associated
      hospitalizations: the tipping point of the iceberg.
AB  - Background: The risk of infection with Anisakis has been recognized for some
      time, but it is now emerging due to major awareness, better diagnostic techniques
      and increasing preference for raw or lightly cooked food. Spain has the second
      highest reported incidence after Japan, though the real anisakidosis burden is
      unknown because of the scarcity of epidemiological data. This study provides a 19
      years review of the anisakidosis related hospitalizations describing
      epidemiological trends and patients' characteristics. Methods: We performed a
      retrospective descriptive study using the Spanish Hospitalization Minimum Data
      Set (CMBD) from 1997 to 2015. Hospitalization rates were calculated and spatial
      distribution of cases and their temporal behavior were assessed. Clinical
      characteristics were described, including related co-diagnoses and procedures.
      Results and conclusions: A total of 2,471 hospital discharges were identified. A
      continuous increasing trend was observed, with several peaks. Most affected
      communities were located in the north-west inland part of the country. Almost 54%
      of hospitalized patients were male, mean age of 51.3 years. Median length of stay
      was 5 days, and the hospitalization median cost around 2,900 euros. Fatal outcome
      occurred in 0.5%. Most frequent co-diagnoses were digestive diseases, mainly
      intestinal obstruction. Urticaria, anaphylactic reaction and angioneurotic edema
      were only recorded in 2.2%, 2.4% and 1.2%, respectively. Knowing that
      hospitalization is unusual in anisakidosis, we offer calculations of the real
      disease burden. Improving disease surveillance in parallel to disease control
      will result useful both in gaining extended disease knowledge and reducing
      morbidity and related-costs.

PMID- 30281079
TI  - Long duration of asymptomatic Mycoplasma genitalium infection after syndromic
      treatment for nongonococcal urethritis.
AB  - Background: Although Mycoplasma genitalium (MG) is an acknowledged cause of
      nongonococcal urethritis (NGU), access to diagnostic testing is limited.
      Syndromic management is common, yet little is known about natural history.
      Methods: Between August 8, 2014-April 15, 2016 a case series of 13 heterosexual
      men >=16 years with MG was identified within a cohort study of men with and
      without NGU attending an urban Sexually Transmitted Diseases Clinic. Men had
      monthly visits for 6-7 months. NGU was defined as >=5 polymorphonuclear
      leukocytes per high power field on urethral Gram stain plus either visible
      urethral discharge or urethral symptoms. Men with NGU received one gram
      azithromycin. Men with persistent NGU received moxifloxacin 400mg x 14 days.
      First-void urine was retrospectively tested for MG using TMA. Resistance
      associated mutations were detected by PCR and sequencing. Organism load was
      determined by quantitative PCR. Results: Sixty-two percent of MG-positive men had
      a macrolide resistance mediating mutation (MRMM) at enrollment; 31% had parC
      mutations (all outside the quinolone resistance determining region). MG persisted
      after azithromycin in seven men, six of whom had MRMM. The median duration of
      persistence in the absence of curative therapy was 143 days (range 21-228). Five
      men experienced symptom resolution after azithromycin but MG persisted for
      another 89-186 days before moxifloxacin. Organism load was somewhat lower in MRMM
      than wild type infections (p=0.16). Conclusions: The high prevalence of macrolide
      resistance and long duration of persistent MG infection after symptom resolution
      highlights the need for diagnostic testing of men with NGU to direct therapy.

PMID- 30281080
TI  - Recent progress in organoid culture to model intestinal epithelial barrier
      functions.
AB  - The intestinal epithelium not only acts as the physical structure that separates
      the intestinal lumen from the body but also actively participates in intestinal
      barrier functions. In the past decade, significant progress has been made in the
      development of culture technologies to maintain intestinal epithelial cells
      (IECs) as various forms of intestinal organoids. As these organoids allow for
      restoration of the physiological composition of IECs, they represent suitable
      models to study the mechanisms of development and differentiation or the
      molecular basis of functions in specific types of IECs, such as goblet cells,
      Paneth cells, tuft cells and M cells. In addition, intestinal organoids are now
      widely used as model systems to investigate the dynamic processes occurring at
      the host-microbe interface and the mutual interactions between IECs and the cells
      involved in the maintenance of local immune homeostasis. In this review article,
      I showcase recent work that has utilized intestinal organoids to study various
      aspects of intestinal epithelial barrier functions.

PMID- 30281081
TI  - Impact of Infectious Disease Consultation on Clinical Management and Mortality in
      Patients with Candidemia.
AB  - Candidemia has a high attributable mortality. The objective of this study was to
      determine the impact of infectious disease consultation on mortality and clinical
      outcomes in candidemia. Infectious disease consultation was associated with
      better adherence to guidelines and improved survival, even in patients with high
      APACHE II scores.

PMID- 30281082
TI  - Clostridium difficile in Immunocompromised Hosts: A Review of Epidemiology, Risk
      Factors, Treatment, and Prevention.
AB  - Clostridium difficile is a significant pathogen in healthcare today, impacting
      both hospitalized and community-based patients. Immunocompromised patients
      experience a high incidence of C. difficile infection, ranging from 6% to 33% in
      the hematology-oncology population, up to 23% among lung transplant recipients,
      and a rate of 7.1-8.3 cases per 1000 patient years in patients with human
      immunodeficiency virus. Recurrence of C. difficile infections among
      immunocompromised patients is also high, with rates up to 40% in both the
      hematology-oncology population and solid organ transplant recipients. This higher
      incidence of C. difficile infection and recurrence is believed to be secondary to
      frequent antimicrobial use, suppressed immune function, increased exposure to
      healthcare settings, and higher prevalence of C. difficile colonization. This
      review summarizes published data describing the epidemiology, risk factors for
      acquisition and infection, treatment, and prevention of C. difficile in
      hematology-oncology, solid organ transplant, and human immunodeficiency virus
      infected patients.

PMID- 30281083
TI  - Drug-free holidays: Compliance, tolerability, and acceptability of a 3-day
      atovaquone/proguanil schedule for pre-travel malaria chemoprophylaxis in
      Australian travellers.
AB  - Background: Poor compliance with chemoprophylaxis is a major contributing factor
      to the risk of malaria in travellers. Pre-travel chemoprophylaxis may improve
      compliance by enabling 'drug-free holidays'. The standard treatment dose of
      atovaquone/proguanil (250mg/100mg, 4 tablets/day for 3 days) provides protection
      against malaria for at least 4 weeks, and could therefore potentially be used for
      pre-travel chemoprophylaxis. In this study, we assessed the compliance,
      tolerability, and acceptability of the 3-day atovaquone/proguanil schedule for
      malarial chemoprophylaxis. Methods: 233 participants were recruited from four
      specialised travel medicine clinics in Australia. Adults travelling to malaria
      endemic areas with low/medium risk for <=4 weeks were enrolled, and prescribed
      the 3-day schedule of atovaquone/proguanil, completed at least one day before
      departure. Questionnaires were used to collect data on demographics, travel
      destination, medication compliance, side effects, and reasons for choosing the 3
      day schedule. The study was registered with the Australian and New Zealand
      Clinical Trials Registry, number ACTRN12616000640404. Results: Overall, 97.7% of
      participants complied with the 3-day schedule. Although side effects were
      reported in 43.3% of the participants, these were well tolerated, and mainly
      occurred during the first and second day. None of the participants developed
      malaria. The main reasons for choosing the 3-day schedule over standard
      chemoprophylaxis options were that it was easier to remember (72.1%), required
      taking fewer tablets (54.0%), and to help scientific research (54.0%).
      Conclusions: The 3-day atovaquone/proguanil schedule had an impressively high
      compliance rate, and was well tolerated and accepted by travellers. Further
      studies are required to assess the effectiveness of this schedule for
      chemoprophylaxis in travellers.

PMID- 30281084
TI  - Deployment and Disaster Medicine in an Undergraduate Teaching Module.
AB  - Introduction: Modern health systems have to respond to a wide variety of
      catastrophic scenarios, from natural disasters to terror attacks. It is
      reasonable to already start educational approaches for physicians in this field
      at medical school level. An approach combining civilian disaster medicine and
      military deployment medicine can be beneficial both for clinical strategies and
      in undergraduate teaching. Materials and Methods: A curricular 4-week teaching
      module on "deployment and disaster medicine," interdisciplinarily combining over
      12 medical specialties, was launched in the summer semester of 2016 at a civilian
      medical school. The course was integrated into the undergraduate curriculum by
      learning spirals. Teaching formats encompassed a total of 72 hours of seminars,
      clinical case discussions, group work, e-Learning, and practical training. The
      students' gain in knowledge was analyzed with pre/post-multiple-choice tests and
      their attitude towards the offer was evaluated. Results: A total of 51 students
      participated in the module over three semesters. The evaluation revealed that the
      students were highly satisfied with the offer and felt motivated to increase
      their engagement with the topic. The students additionally valued the course as a
      good means of deepening the core curriculum. The pre/post-tests showed a
      significant gain in knowledge among the students (p < 0.001). Conclusions: The
      course presented received an overall highly positive feedback from the
      participating students. The experience of this approach suggests that the
      combination of civilian and military knowledge and expertise in deployment and
      disaster medicine may lead to the creation of effective interdisciplinary course
      concepts.

PMID- 30281085
TI  - Insecticidal Activity of Local Plants Essential Oils Against Laboratory and Field
      Strains of Anopheles gambiae s. l. (Diptera: Culicidae) From Burkina Faso.
AB  - The emergence and intensification of resistance to insecticides in malaria vector
      populations is the main obstacle to insecticide-based control efforts. The main
      objective of this study was to evaluate the larvicidal and adulticidal properties
      of the essential oils (EOs) of Ocimum canum, Hyptis suaveolens, Hyptis spicigera,
      and Lantana camara on field-collected, pyrethroids-resistant mosquitoes, local
      laboratory strains, and susceptible 'Kisumu' strain of Anopheles gambiae (Meigen)
      (Diptera: Culicidae) populations. Larvae and adults of these mosquitoes were
      challenged against four EOs. The mortality rates of larvae and adults were
      assessed 24 h after exposure to the EOs. Species identifications and detection of
      the L1014F and L1014S kdr mutations and the 1575Y super-kdr mutation were carried
      out using polymerase chain reaction on the pyrethroid-resistant mosquitoes from
      the field. EO compositions were analyzed by gas chromatography and mass
      spectrometry. Monoterpene hydrocarbons were the major components of H. suaveolens
      and H. spicigera EOs (49.8%) and (69.6%), respectively, whereas oxygenated
      monoterpenes (68.7%) were predominant in the O. canum EO. For L. camara, the
      component yields were variable, but it was the most effective EO against all
      strains. The LC50 values for the larvae were 7.73 and 25.63 ppm for the
      susceptible 'Kisumu' and resistant field strains, respectively. The LC50 for
      adults was 0.24% for the susceptible strain and 1.98% for the resistant strain.
      Molecular analysis confirmed the presence of L1014F and N1575Y mutations in
      resistant Anopheles arabiensis and Anopheles coluzzii mosquitoes from the field.
      Our results highlighted the potential of the EOs of local plants as insecticides
      against resistant and susceptible strains of An. gambiae populations.

PMID- 30281086
TI  - Single-Session Mobile-Augmented Intervention in Serious Mental Illness: A Three
      Arm Randomized Controlled Trial.
AB  - Psychosocial interventions for serious mental illness are resource intensive and
      poorly accessible. Brief interventions (eg, single session) that are augmented by
      follow-on automated mobile health intervention may expand treatment access. This
      was a randomized single-blind controlled trial with 255 individuals diagnosed
      with schizophrenia or bipolar disorder. Participants were randomized to one of
      three conditions: CBT2go, which combined one individual session of cognitive
      behavioral therapy with automated thought challenging/adaptive behavior delivered
      through mobile devices; Self-Monitoring (SM), which combined single-session
      illness psychoeducation with self-monitoring of symptoms; and treatment-as-usual
      (TAU). Participants were assessed at baseline, 6 weeks (midpoint), 12 weeks
      (posttreatment), and 24 weeks (follow-up) with our primary outcome global
      psychopathology (Brief Psychiatric Rating Scale-expanded version [BPRS-24]), and
      secondary outcomes community functioning (Specific Level of Function; SLOF) and
      defeatist performance beliefs (DPBs). We also collected data on adverse events.
      Outcome analyses on the primary outcome, BPRS Total score, indicated a
      significant time (0-24 wk) by group interaction with significant but modest
      improvement comparing two active conditions (CBT2go and SM) relative to TAU.
      Effects of CBT2go were not different from SM. There was a significant time *
      group interaction with better SLOF scores in CBT2go across 24 weeks, but not in
      SM. There were no time-by-group effects on DPBs. DPBs decreased in the CBT2go
      condition but not in SM. These results indicated that single intervention
      augmented by mobile intervention was feasible and associated with small yet
      sustained effects on global psychopathology and, when inclusive of CBT, community
      function compared with usual care.

PMID- 30281087
TI  - New applications of sonoelastography in rheumatology: where are we now?
AB  - Ultrasound elastography (UE) is a non-invasive imaging method that allows the
      assessment of tissue elastic property. Different UE techniques are currently
      available (i.e. strain UE and acoustic radiation force impulse UE), with several
      potential clinical applications. Recent studies investigated the role of UE in
      two systemic rheumatic diseases and psoriasis. This research added interesting
      information to the already known applications of UE in the assessment of
      tendinopathies. In SS, acoustic radiation force impulse UE has shown a potential
      role in the diagnosis of the disease, with lower sensitivity than and similar
      specificity to salivary gland histology. In SSc, a potential use of UE in
      screening pre-clinical disease has been reported. In psoriasis, the use of strain
      UE in evaluating treatment response has been highlighted. UE is a promising tool
      in rheumatology, with a potential role in the evaluation of various tissues and
      pathologies.

PMID- 30281088
TI  - Metacognition, Personal Distress, and Performance-Based Empathy in Schizophrenia.
AB  - Background: People with schizophrenia experience significant deficits in the
      kinds of empathic skills that are the foundation for interpersonal relationships.
      Researchers have speculated that deficits in empathic skills in schizophrenia may
      be related to disturbances in metacognition and heightened levels of personal
      distress. To explore this issue, this study examined whether better metacognition
      and reduced personal distress would be associated with improved performance on
      cognitive and affective empathy tasks. Further, we tested whether metacognition
      moderated the relationship between personal distress and empathy. Method: Fifty
      eight participants with schizophrenia-spectrum disorders receiving community
      based treatment completed a self-report questionnaire of personal distress, a
      performance-based measure of empathy, and an observer-rated interview to assess
      metacognitive capacity. Results: Correlation analyses revealed that metacognitive
      capacity, but not personal distress, was significantly associated with cognitive
      and affective empathy performance. Moderation results suggest the relationship
      between personal distress and affective empathy performance was significant for
      those with low metacognition, but that the relationship was the opposite of
      hypotheses-increased personal distress predicted better performance. This
      relationship changed at higher levels of metacognition, when increased personal
      distress became associated with reduced performance. Conclusions: This study is
      the first of its kind to examine performance-based empathy with metacognition and
      personal distress. Results suggest interventions targeted to improve
      metacognition may be useful in enhancing empathic skills.

PMID- 30281089
TI  - Mortality and causes of death across the systemic connective tissue diseases and
      the primary systemic vasculitides.
AB  - Objectives: Studies assessing relative mortality risks across the spectrum of
      systemic inflammatory rheumatic diseases are largely missing. In this study, we
      wanted to estimate standard mortality ratios (SMRs) and causes of death in an
      ethnically homogeneous cohort covering all major CTDs and primary systemic
      vasculitides (PSVs). Methods: We prospectively followed all incident CTD and PSV
      cases included in the Norwegian CTD and vasculitis registry (NOSVAR) between 1999
      and 2015. Fifteen controls for each patient matched for sex and age were randomly
      drawn from the Norwegian National Population Registry. Causes of death were
      obtained from the National Cause of Death Register, death certificates and
      hospital charts. Results: The cohort included 2140 patients (1534 with CTD, 606
      with PSV). During a mean follow-up time of 9 years, 279 of the patients (13%)
      died, compared with 2864 of 32 086 (9%) controls (P < 0.001). Ten years after
      diagnosis, the lowest survival was 60% in dcSSc, 73% in anti-synthetase syndrome
      (ASS) and 75% in lcSSc. In the CTD group, the highest SMRs were observed in dcSSc
      (SMR 5.8) and ASS (SMR 4.1). In the PSV group, Takayasu arteritis (SMR 2.5) and
      ANCA-associated vasculitis (SMR 1.5) had the highest SMRs. Major causes of death
      were cardiovascular disease (CTD 27%, PSV 28%), neoplasms (CTD 25%, PSV 27%),
      chronic respiratory disease (CTD 20%, PSV10%) and infections (CTD 9%, PSV 16%).
      Conclusion: We observed premature deaths across the spectrum of CTDs and PSVs,
      with highest SMRs in dcSSc and ASS. The overall mortality was highest in the CTD
      group.

PMID- 30281090
TI  - Polygenic Risk Score for Schizophrenia and Face-Processing Network in Young
      Adulthood.
AB  - Development of schizophrenia relates to both genetic and environmental factors.
      Functional deficits in many cognitive domains, including the ability to
      communicate in social interactions and impaired recognition of facial
      expressions, are common for patients with schizophrenia and might also be present
      in individuals at risk of developing schizophrenia. Here we explore whether an
      individual's polygenic risk score (PRS) for schizophrenia is associated with the
      degree of interregional similarities in blood oxygen level-dependent (BOLD)
      signal and gray matter volume of the face-processing network and whether the
      exposure to early adversity moderates this association. A total of 90 individuals
      (mean age 22 years, both functional and structural data available) were used for
      discovery analyses, and 211 individuals (mean age 26 years, structural data
      available) were used for replication of the structural findings. Both samples
      were drawn from the Northern Finland Birth Cohort 1986. We found that the degree
      of interregional similarities in BOLD signal and gray matter volume vary as a
      function of PRS; lowest interregional correlation (both measures) was observed in
      individuals with high PRS. We also replicated the gray matter volume finding. We
      did not find evidence for an interaction between early adversity and PRS on the
      interregional correlation of BOLD signal and gray matter volume. We speculate
      that the observed group differences in PRS-related correlations in both
      modalities may result from differences in the concurrent functional engagement of
      the face-processing regions over time, eg, via differences in exposure to social
      interaction with other people.

PMID- 30281091
TI  - Cis D4Z4 repeat duplications associated with facioscapulohumeral muscular
      dystrophy type 2.
AB  - Facioscapulohumeral muscular dystrophy, known in genetic forms FSHD1 and FSHD2,
      is associated with D4Z4 repeat array chromatin relaxation and somatic
      derepression of DUX4 located in D4Z4. A complete copy of DUX4 is present on 4qA
      chromosomes, but not on the D4Z4-like repeats of chromosomes 4qB or 10. Normally,
      the D4Z4 repeat varies between 8 and 100 units, while in FSHD1 it is only 1-10
      units. In the rare genetic form FSHD2, a combination of a 4qA allele with a D4Z4
      repeat size of 8-20 units and heterozygous pathogenic variants in the chromatin
      modifier SMCHD1 causes DUX4 derepression and disease. In this study, we
      identified 11/79 (14%) FSHD2 patients with unusually large 4qA alleles of 21-70
      D4Z4 units. By a combination of Southern blotting and molecular combing, we show
      that 8/11 (73%) of these unusually large 4qA alleles represent duplication
      alleles in which the long D4Z4 repeat arrays are followed by a small FSHD-sized
      D4Z4 repeat array duplication. We also show that these duplication alleles are
      associated with DUX4 expression. This duplication allele frequency is
      significantly higher than in controls (2.9%), FSHD1 patients (1.4%) and in FSHD2
      patients with typical 4qA alleles of 8-20 D4Z4 units (1.5%). Segregation analysis
      shows that, similar to typical 8-20 units FSHD2 alleles, duplication alleles only
      cause FSHD in combination with a pathogenic variant in SMCHD1. We conclude that
      cis duplications of D4Z4 repeats explain DUX4 expression and disease presentation
      in FSHD2 families with unusual long D4Z4 repeats on 4qA chromosomes.

PMID- 30281092
TI  - Cmah-dystrophin deficient mdx mice display an accelerated cardiac phenotype that
      is improved following peptide-PMO exon skipping treatment.
AB  - Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin protein,
      leading to progressive muscle weakness and premature death due to respiratory
      and/or cardiac complications. Cardiac involvement is characterized by progressive
      dilated cardiomyopathy, decreased fractional shortening and metabolic dysfunction
      involving reduced metabolism of fatty acids-the major cardiac metabolic
      substrate. Several mouse models have been developed to study molecular and
      pathological consequences of dystrophin deficiency, but do not recapitulate all
      aspects of human disease pathology and exhibit a mild cardiac phenotype. Here we
      demonstrate that Cmah (cytidine monophosphate-sialic acid hydroxylase)-deficient
      mdx mice (Cmah-/-;mdx) have an accelerated cardiac phenotype compared to the
      established mdx model. Cmah-/-;mdx mice display earlier functional deterioration,
      specifically a reduction in right ventricle (RV) ejection fraction and stroke
      volume (SV) at 12 weeks of age and decreased left ventricle diastolic volume with
      subsequent reduced SV compared to mdx mice by 24 weeks. They further show earlier
      elevation of cardiac damage markers for fibrosis (Ctgf), oxidative damage (Nox4)
      and haemodynamic load (Nppa). Cardiac metabolic substrate requirement was
      assessed using hyperpolarized magnetic resonance spectroscopy indicating
      increased in vivo glycolytic flux in Cmah-/-;mdx mice. Early upregulation of
      mitochondrial genes (Ucp3 and Cpt1) and downregulation of key glycolytic genes
      (Pdk1, Pdk4, Ppara), also denote disturbed cardiac metabolism and shift towards
      glucose utilization in Cmah-/-;mdx mice. Moreover, we show long-term treatment
      with peptide-conjugated exon skipping antisense oligonucleotides (20-week
      regimen), resulted in 20% cardiac dystrophin protein restoration and
      significantly improved RV cardiac function. Therefore, Cmah-/-;mdx mice represent
      an appropriate model for evaluating cardiac benefit of novel DMD therapeutics.

PMID- 30281093
TI  - Outcome of Pregnancies in Female Patients With Inflammatory Bowel Diseases
      Treated With Vedolizumab.
AB  - Background and Aims: Vedolizumab is an IgG1 anti-alpha4beta7 integrin antibody
      approved for the treatment of inflammatory bowel diseases [IBD], but without
      clear safety data during conception, pregnancy and nursing. Animal studies showed
      that mucosal vascular addressin cell adhesion molecule 1 [MAdCAM-1] is expressed
      by maternal vessels in the placenta and recruits alpha4beta7-expressing cells
      that are considered important for maternal/fetal tolerance. Blocking this
      interaction by vedolizumab might affect this process. We aimed to evaluate
      pregnancy outcomes in vedolizumab-treated female IBD patients. Methods: We
      conducted a retrospective, multicentre Belgian observational study. Details on
      disease activity, prenatal complications, delivery and neonatal outcome were
      collected through a case report form. Results: Twenty-four pregnancies were
      reported. Five women had active disease at conception and one patient flared
      during pregnancy. There were 23 live births. Complications were observed in 25%
      of pregnancies [premature rupture of membranes, pre-eclampsia, miscarriage,
      elective termination and stillbirth] and in 35% of infants [prematurity, intra
      uterine growth retardation, small for gestational age and congenital
      malformations including hip dysplasia, pulmonary valve stenosis and Hirschprung's
      disease]. Vedolizumab was continued throughout pregnancy in two females and
      stopped in the 1st and 2nd trimester in five and 16 patients, respectively. For
      live born children, the median [interquartile range] gestational age, weight and
      Apgar score 5 min after birth were 39 [37-39.6] weeks, 3270 [3080-3585] grams and
      10 [9-10], respectively. Conclusions: Although several complications were
      observed, both in mothers and in newborns, no firm conclusions can be drawn.
      Awaiting prospective and controlled registries, vigilance and strict follow-up of
      pregnant patients treated with vedolizumab seems mandatory.

PMID- 30281094
TI  - Hit Improves Aerobic Capacity Without a Detrimental Decline in Blood Glucose in
      People with Type 1 Diabetes.
AB  - AIMS: To investigate whether 1) six weeks of high-intensity interval training
      (HIT) induces similar improvements in cardio-metabolic health markers as moderate
      intensity continuous training (MICT) in people with type 1 diabetes, and 2)
      whether HIT abolishes acute reductions in plasma glucose observed following MICT
      sessions. METHODS: Fourteen sedentary individuals with type 1 diabetes (n=7 per
      group) completed six weeks of HIT or MICT 3 times per week. Pre- and post
      training measurements were made of 24h interstitial glucose profiles (using
      continuous glucose monitors (CGMS)) and cardio-metabolic health markers (VO2peak,
      blood lipid profile and aortic pulse wave velocity; aPWV). Capillary blood
      glucose concentrations were assessed before and after exercise sessions
      throughout the training programme to investigate changes in blood glucose during
      exercise in the fed state. RESULTS: Six weeks of HIT or MICT increased VO2peak by
      14% and 15%, respectively (P<0.001), and aPWV by 12% (P<0.001), with no
      difference between groups. 24h CGMS data revealed no differences in incidence or
      percentage of time spent in hypoglycaemia following training in either group
      (P>0.05). In the fed state, the mean change in capillary blood glucose
      concentration during the HIT sessions was -0.2+/-0.5 mmol/L, whereas blood
      glucose change was -5.5+/-0.4 mmol/L during MICT. CONCLUSIONS: Six weeks of HIT
      improved VO2peak and aortic PWV to a similar extent as MICT. The finding that
      blood glucose remained stable during HIT in the fed state, but consistently fell
      during MICT, suggests that HIT may be the preferred training mode for some people
      with type 1 diabetes.

PMID- 30281095
TI  - Therapeutic role of appendectomy in ulcerative colitis: a tangible perspective?

PMID- 30281096
TI  - Solve the problems for better health-from quality indicators to system audits.

PMID- 30281097
TI  - Caring for veterans in US civilian primary care: qualitative interviews with
      primary care providers.
AB  - Background: Non-VA health care providers in the USA have been called upon to
      screen patients for veteran status as a means to better identify military-related
      health sequelae. Despite this recognized need, many service members are still not
      being asked about veteran status. Objective: The purpose of this research was to
      qualitatively assess, from non-VA primary care providers' point-of-view, barriers
      to providing care to veterans, the training providers perceive as most useful and
      the tools and translational processes they think would be most valuable in
      increasing military cultural competency. Methods: Semi-structured qualitative
      interviews, with non-VA primary care providers (N = 10) as part of a larger
      quantitative study of primary care providers' attitudes around veteran care.
      Interviews asked about providers' approach to addressing veteran status in their
      practice and their thoughts on how to address the needs of this population.
      Qualitative data were analyzed using a thematic content analysis approach.
      Results: Three major themes were identified: (i) barriers to caring for patients
      who are identified as veterans, (ii) thoughts on tools that might help better
      identify and screen veteran patients and (iii) thoughts on translating and
      implementing new care processes for veteran patients into everyday practice.
      Conclusions: Our study identified barriers related to non-VA providers' ability
      to care for veterans among their patients and possible mechanisms for improving
      recognition of veterans in civilian health care settings. There is a need for
      further research to understand how assessment, screening and follow up care for
      veteran patients is best implemented into civilian primary care settings.

PMID- 30281098
TI  - Giant syphilitic aortic pseudoaneurysm with extrinsic compression of the left
      atrium, right pulmonary artery, and oesophagus.

PMID- 30281099
TI  - Genome-wide meta-analysis identifies BARX1 and EML4-MTA3 as new loci associated
      with infantile hypertrophic pyloric stenosis.
AB  - Infantile hypertrophic pyloric stenosis (IHPS) is a disorder of young infants
      with a population incidence of ~2/1000 live births, caused by hypertrophy of the
      pyloric sphincter smooth muscle. Reported genetic loci associated with IHPS
      explain only a minor proportion of IHPS risk. To identify new risk loci, we
      carried out a genome-wide meta-analysis on 1395 surgery-confirmed cases and 4438
      controls, with replication in a set of 2427 cases and 2524 controls. We
      identified and replicated six independent genomic loci associated with IHPS risk
      at genome wide significance (P<5x10-8), including novel associations with two
      SNPs. One of these SNPs, rs6736913 (odds ratio [OR] = 2.32; P = 3.0x10-15), is a
      low frequency missense variant in EML4 at 2p21. The second SNP, rs1933683 (OR =
      1.34; P = 3.1*10-9) is 1 kb downstream of BARX1 at 9q22.32, an essential gene for
      stomach formation in embryogenesis. Using the genome-wide complex trait analysis
      (GCTA) method, we estimated the IHPS SNP heritability to be 30%, and using the LD
      score regression method, we found support for a previously reported genetic
      correlation of IHPS with lipid metabolism. By combining the largest collection of
      IHPS cases to date (3822 cases), with results generalized across populations of
      different ancestry, we elucidate novel mechanistic avenues of IHPS disease
      architecture.

PMID- 30281100
TI  - Extrapolation of in vitro structural alerts for mutagenicity to the in vivo
      endpoint.
AB  - As part of the hazard and risk assessment of chemicals in man, it is important to
      assess the ability of a chemical to induce mutations in vivo. Because of the
      commonalities in the molecular initiating event, mutagenicity in vitro can
      correlate well to the in vivo endpoint for certain compound classes; however, the
      difficulty lies in identifying when this correlation holds true. In silico alerts
      for in vitro mutagenicity may therefore be used as the basis for alerts for
      mutagenicity in vivo where an expert assessment is carried out to establish the
      relevance of the correlation. Taking this into account, a data set of publicly
      available transgenic rodent gene mutation assay data, provided by the National
      Institute of Health Sciences of Japan, was processed in the expert system Derek
      Nexus against the in vitro mutagenicity endpoint. The resulting predictivity was
      expertly reviewed to assess the validity of the observed correlations in activity
      and mechanism of action between the two endpoints to identify suitable in vitro
      alerts for extension to the in vivo endpoint. In total, 20 alerts were extended
      to predict in vivo mutagenicity, which has significantly improved the coverage of
      this endpoint in Derek Nexus against the data set provided. Updating the Derek
      Nexus knowledge base in this way led to an increase in sensitivity for this data
      set against this endpoint from 9% to 66% while maintaining a good specificity of
      89%.

PMID- 30281101
TI  - 90th Anniversary Commentary: Dietary Diversity Is the Cornerstone of Good
      Nutrition.

PMID- 30281102
TI  - 90th Anniversary Commentary: The AIN-93 Purified Diets for Laboratory Rodents-The
      Development of a Landmark Article in The Journal of Nutrition and Its Impact on
      Health and Disease Research Using Rodent Models.

PMID- 30281103
TI  - 90th Anniversary Commentary: Caloric Restriction Effects on Aging.

PMID- 30281104
TI  - 90th Anniversary Commentary: Measurement of Energy Expenditure in Free-Living
      Humans by Using Doubly Labeled Water.

PMID- 30281105
TI  - High-Sugar, High-Saturated-Fat Dietary Patterns Are Not Associated with
      Depressive Symptoms in Middle-Aged Adults in a Prospective Study.
AB  - Background: The consumption of unhealthy "Western" dietary patterns has been
      previously associated with depressive symptoms in different populations.
      Objective: We examined whether high-sugar and high-saturated-fat dietary patterns
      are associated with depressive symptoms over 5 y in a British cohort of men and
      women. Methods: We used data from the Whitehall II study in 5044 individuals
      (aged 35-55 y). Diet was assessed at phase 7 (2003-2004) using a validated food
      frequency questionnaire. Dietary patterns were derived by using reduced rank
      regression with sugar, saturated fat, and total fat as response variables. The
      Center for Epidemiological Studies-Depression (CES-D) scale was used to assess
      depressive symptoms (CES-D sum score >=16 and/or use of antidepressant
      medication) at phase 7 and at phase 9 (2008-2009). We applied logistic regression
      analyses to test the association between dietary patterns and depressive
      symptoms. All analyses were stratified by sex. Results: In total, 398 cases of
      recurrent and 295 cases of incident depressive symptoms were observed. We
      identified 2 dietary patterns: a combined high-sugar and high-saturated-fat
      (HSHF) and a high-sugar dietary pattern. No association was observed between the
      dietary patterns and either incidence of or recurrent depressive symptoms in men
      or women. For example, higher consumption of the HSHF dietary pattern was not
      associated with recurrent depressive symptoms in men (model 3, quartile 4: OR:
      0.67; 95% CI: 0.36, 1.23; P-trend = 0.13) or in women (model 3, quartile 4: OR:
      1.26; 95% CI: 0.58, 2.77; P-trend = 0.97). Conclusion: Among middle-aged men and
      women living in the United Kingdom, dietary patterns containing high amounts of
      sugar and saturated fat are not associated with new onset or recurrence of
      depressive symptoms.

PMID- 30281106
TI  - Compared with Cow Milk, a Growing-Up Milk Increases Vitamin D and Iron Status in
      Healthy Children at 2 Years of Age: The Growing-Up Milk-Lite (GUMLi) Randomized
      Controlled Trial.
AB  - Background: Iron deficiency (ID) and vitamin D deficiency (VDD) are significant
      pediatric health issues in New Zealand and Australia and remain prevalent
      micronutrient deficiencies in young children globally. Objective: We aimed to
      investigate the effect of a micronutrient-fortified, reduced-energy growing-up
      milk (GUMLi) compared with cow milk (CM) consumed for 1 y on dietary iron and
      vitamin D intakes and the status of New Zealand and Australian children at 2 y of
      age. Methods: The GUMLi Trial was a multicenter, double-blind, randomized
      controlled trial in 160 healthy 1-y-old New Zealand and Australian children
      conducted in 2015-2017. Participants were randomly assigned 1:1 to receive GUMLi
      (1.7 mg Fe/100 mL; 1.3 ug cholecalciferol/100 mL) or CM (0.02 mg Fe/100 mL; 0.06
      ug cholecalciferol/100 mL) for 12 mo. Secondary outcomes, reported here, included
      change in dietary iron and vitamin D intakes, iron status, and 25-hydroxyvitamin
      D [25(OH)D] concentrations from blood samples at age 2 y. All regression models
      were adjusted for baseline outcome and study center. Results: GUMLi was a large
      contributor to dietary intakes of iron and vitamin D after 12 mo when compared
      with intakes from food and CM. The adjusted mean difference between groups for
      serum ferritin concentrations was 17.8 ug/L (95% CI: 13.6, 22.0 ug/L; P <
      0.0001), and for 25(OH)D it was 16.6 nmol/L (95% CI: 9.9, 23.3 nmol/L; P <
      0.0001). After 12 mo, ID was present in 16 (24%) participants in the CM group and
      5 (7%) participants in the GUMLi group (P = 0.009), and the prevalence of VDD in
      the CM group increased to 14% (n = 10) and decreased to 3% (n = 2) (P = 0.03) in
      the GUMLi group. Conclusion: In comparison with CM, GUMLi significantly improved
      dietary iron and vitamin D intakes and the iron and vitamin D status of healthy
      children at 2 y of age. This trial was registered with the Australian New Zealand
      Clinical Trials Registry (www.anzctr.org.au) as ACTRN12614000918628.

PMID- 30281107
TI  - 90th Anniversary Commentary: Obesity among Offspring of US Immigrants: After 20
      Years, a Need to Safeguard Children from the Obesogenic Environment.

PMID- 30281108
TI  - 90th Anniversary Commentary: Consumption of Sweetened Beverages Predicts the
      Occurrence of Type 2 Diabetes.

PMID- 30281109
TI  - 90th Anniversary Commentary: Vitamin D Is Critical for Human Nutrition, but
      Research Is Still Needed to Identify Optimal Blood Concentrations and Intake
      Levels for Human Health.

PMID- 30281110
TI  - 90th Anniversary Commentary: Beginning of the Selenoprotein Era.

PMID- 30281111
TI  - 90th Anniversary Commentary: Malnutrition Affects Cellular Growth and Competency;
      Propositions by Myron Winick.

PMID- 30281112
TI  - Hepatic Expression of PEMT, but Not Dietary Choline Supplementation, Reverses the
      Protection against Atherosclerosis in Pemt-/-/Ldlr-/- Mice.
AB  - Background: Phosphatidylethanolamine N-methyltransferase (PEMT) converts
      phosphatidylethanolamine to phosphatidylcholine. Pemt-/-/low density lipoprotein
      receptor (Ldlr)-/- mice have significantly reduced plasma lipids and are
      protected against atherosclerosis. Recent studies have shown that choline can be
      metabolized by the gut flora into trimethylamine-N-oxide (TMAO), which is an
      emerging risk factor for atherosclerosis. Objective: The objective of this study
      was to determine whether ectopic hepatic PEMT expression or choline
      supplementation would promote atherosclerosis in Pemt-/-/Ldlr-/- mice. Methods:
      Male 8- to 10-wk-old Pemt+/+/Ldlr-/- (SKO) and Pemt-/-/Ldlr-/- (DKO) mice were
      injected with an adeno-associated virus (AAV) expressing green fluorescent
      protein (GFP) or human PEMT and fed a Western diet (40% of calories from fat,
      0.5% cholesterol) for 8 wk. In a separate experiment, 8- to 10-wk-old SKO and
      half of the DKO male mice were fed a Western diet with normal (3 g/kg) choline
      for 12 wk. The remaining DKO mice [choline-supplemented (CS) DKO] were fed a CS
      Western diet (10 g choline/kg). Plasma lipid concentrations, choline metabolites,
      and aortic atherosclerosis were measured. Results: Plasma cholesterol, plasma
      TMAO, and aortic atherosclerosis were reduced by 60%, 40%, and 80%, respectively,
      in DKO mice compared with SKO mice. AAV-PEMT administration increased plasma
      cholesterol and TMAO by 30% and 40%, respectively, in DKO mice compared with AAV
      GFP-treated DKO mice. Furthermore, AAV-PEMT-injected DKO mice developed
      atherosclerotic lesions similar to SKO mice. In the second study, there was no
      difference in atherosclerosis or plasma cholesterol between DKO and CS-DKO mice.
      However, plasma TMAO concentrations were increased 2.5-fold in CS-DKO mice
      compared with DKO mice. Conclusions: Reintroducing hepatic PEMT reversed the
      atheroprotective phenotype of DKO mice. Choline supplementation did not increase
      atherosclerosis or plasma cholesterol in DKO mice. Our data suggest that plasma
      TMAO does not induce atherosclerosis when plasma cholesterol is low. Furthermore,
      this is the first report to our knowledge that suggests that de novo choline
      synthesis alters TMAO status.

PMID- 30281113
TI  - 90th Anniversary Commentary: The mTORC1 Complex-A Central Player in the Control
      and Regulation of Amino Acid Sufficiency.

PMID- 30281114
TI  - Intravenous Triacylglycerol Infusion Promotes Ceramide Accumulation and Hepatic
      Steatosis in Dairy Cows.
AB  - Background: Increased plasma free fatty acids (FFAs) impair insulin sensitivity
      in dairy cows via unknown mechanisms. In nonruminants, saturated FFAs upregulate
      the hepatic synthesis and secretion of ceramide, which inhibits insulin action.
      Objective: We aimed to determine whether an increase in plasma FFAs promotes
      hepatic and plasma ceramide accumulation in dairy cows. Methods: Six nonpregnant,
      nonlactating Holstein cows were used in a study with a crossover design and
      treatments consisting of intravenous infusion of either saline (control) or
      triacylglycerol emulsion (TG; 20 g/h) for 16 h. The feeding level was set at 120%
      of energy requirements. Blood was collected at regular intervals and liver was
      biopsied at 16 h. Ceramides, monohexosylceramides (Glc/Gal-Cer),
      lactosylceramides (LacCer), and sphingomyelins (SMs) in plasma and liver were
      profiled. Hepatic expression of ceramide synthases was determined. Data were
      analyzed with the use of mixed models, regressions, and Spearman rank
      correlations. Results: After 16 h of infusion, plasma FFA concentrations were >5
      fold and liver triacylglycerol concentrations were 4-fold greater in TG cows,
      relative to control. Plasma total and very long-chain ceramide (e.g., C24:0
      ceramide) concentrations increased ~4-fold in TG over control by hour 16 of
      infusion, while C16:0-ceramide were not modified by TG. Infusion of TG increased
      plasma Glc/Gal-Cer (e.g., C16:0-Glc/Gal-Cer, 4-fold by hour 16) relative to
      control, but did not alter LacCer or SM concentrations. Hepatic ceramide
      concentrations increased with TG relative to control (e.g., C24:0-ceramide by 1.7
      fold). Hepatic expression of ceramide synthase 2 was 60% greater after TG
      infusion compared with the control. Circulating ceramides were related to
      circulating FFA and hepatic triacylglycerol concentrations (e.g., C24:0-ceramide,
      rho = 0.73 and 0.80, respectively; P < 0.001). Conclusion: Hepatic ceramide
      synthesis is associated with elevations in circulating FFAs and hepatic
      triacylglycerol during the induction of hyperlipidemia in dairy cows. This work
      supports the emerging evidence for the role of ceramide during hepatic steatosis
      and insulin antagonism in cows.

PMID- 30281115
TI  - 90th Anniversary Commentary: omega-3 Fatty Acids, Cytokines, and Lymphocyte
      Proliferation in Young and Older Women.

PMID- 30281116
TI  - Erratum.

PMID- 30281118
TI  - Erratum.

PMID- 30281117
TI  - 90th Anniversary Commentary: Setting the Standard for Monitoring Dietary
      Supplement Use in the United States.

PMID- 30281119
TI  - Erratum.

PMID- 30281121
TI  - Erratum.

PMID- 30281120
TI  - 90th Anniversary Commentary: Amino Acid Imbalances: Still in the Balance.

PMID- 30281122
TI  - 90th Anniversary Commentary: Moderate Folate Depletion Increases Plasma
      Homocysteine and Decreases Lymphocyte DNA Methylation in Postmenopausal Women.

PMID- 30281123
TI  - 90th Anniversary Commentary: Diet Quality Indexes in Nutritional Epidemiology
      Inform Dietary Guidance and Public Health.

PMID- 30281124
TI  - 90th Anniversary Commentary: Prebiotics in Infancy for Allergy Prevention:
      Promising Findings, but No Consensus.

PMID- 30281125
TI  - Erratum.

PMID- 30281126
TI  - Chronic inflammation in end-stage renal disease and dialysis.
AB  - Under normal conditions, inflammation is a protective and physiological response
      to various harmful stimuli. However, in several chronic debilitating disorders,
      such as chronic kidney disease, inflammation becomes maladaptive, uncontrolled
      and persistent. Systemic persistent inflammation has, for almost 20 years, been
      recognized as a major contributor to the uraemic phenotype (such as
      cardiovascular disease, protein energy wasting, depression, osteoporosis and
      frailty), and a predictor of cardiovascular and total mortality. Since
      inflammation is mechanistically related to several ageing processes
      (inflammageing), it may be a major driver of a progeric phenotype in the uraemic
      milieu. Inflammation is likely the consequence of a multifactorial aetiology and
      interacts with a number of factors that emerge when uraemic toxins accumulate.
      Beside interventions aiming to decrease the production of inflammatory molecules
      in the uraemic milieu, novel strategies to increase the removal of large middle
      molecules, such as expanded haemodialysis, may be an opportunity to decrease the
      inflammatory allostatic load associated with retention of middle molecular weight
      uraemic toxins.

PMID- 30281127
TI  - Expanded haemodialysis: news from the field.
AB  - Expanded haemodialysis (HDx) has emerged as a promising solution to improve
      haemodialysis effectiveness. A medium cut-off membrane allows the removal of a
      wider range of uraemic toxins. However, little is known about the potential
      interesting applications of HDx therapy. Feedback from the first routine use of
      HDx therapy under real-life conditions in European facilities was excellent for
      priming and rinse back. There was no adverse event after 5191 HDx treatments.
      Patients suffering from itching, restless legs syndrome, persistent asthenia or
      malnourishment could benefit from HDx therapy. Moreover, we discuss here the
      promising applications in which HDx could be valuable (myeloma, rhabdomyolysis or
      cardiovascular diseases). This enthusiastic message is mitigated by reminding why
      and how prudence should be taken in the design of future HDx studies.

PMID- 30281128
TI  - Clinical evidence on haemodiafiltration.
AB  - Haemodiafiltration (HDF) combines diffusive and convective solute removal in a
      single treatment session. HDF provides a greater removal of higher molecular
      weight uraemic retention solutes than conventional high-flux haemodialysis (HD).
      Recently completed randomized clinical trials suggest better patient survival
      with online HDF. The treatment is mainly used in Europe and Japan. This review
      gives a brief overview of the presently available evidence of the effects of HDF
      on clinical end points, it speculates on possible mechanisms of a beneficial
      effect of HDF as compared with standard HD and ends with some perspectives for
      the future.

PMID- 30281129
TI  - Current approaches to middle molecule removal: room for innovation.
AB  - Aggressive removal of middle molecules or larger low-molecular-weight proteins
      (LMWPs) has been a growing concern following studies on their harmful effects on
      the mortality and morbidity of chronic dialysis patients. To remove larger LMWPs
      and some protein-bound uremic toxins (PBUTs), high- and medium-cutoff (HCOs and
      MCOs, respectively) membranes, convective therapy and protein adsorptive
      membranes are available. When we use HCO or MCO membranes for convective therapy,
      we have to take care to avoid massive albumin leakage during a dialysis session.
      Convection volume is an important element to increase middle molecule removal;
      however, a larger convection volume has a risk of larger leakage of albumin.
      Predilution hemodiafiltration is a useful measurement to increase larger LMWPs
      without massive albumin leakage. beta2-microglobulin (B2M), alpha1-microglobulin
      (A1M) and albumin leakage during a dialysis session are useful parameters for
      assessing middle-molecule removal. Reduction ratios of B2M >80% and of A1M >35%
      are favorable to improve severe dialysis-related symptoms. The efficacy of middle
      molecule removal should be evaluated in comparison with clinical outcomes,
      mortality, morbidity and the improvement of dialysis-related symptoms. Recently
      some dialysis-related symptoms such as sleep disturbance, skin itchiness and
      dialysis hypotension have been recognized as good surrogate makers for mortality.
      Further studies to evaluate the relationship between middle molecule or PBUTs
      removal and the improvement of patient symptoms should be performed in well
      designed randomized controlled trials.

PMID- 30281130
TI  - Membrane innovation: closer to native kidneys.
AB  - Modern methods in analytical biochemistry have established that uraemia is
      associated with the retention of proteins, both in their native state and post
      translationally modified, over a wide range of molecular weights up to 60 kDa.
      Evidence is accumulating that these higher molecular weight retention solutes are
      important uraemic toxins, and therapies such as online haemodiafiltration (HDF),
      which enhance their removal, are associated with improved outcomes. However, HDF
      has limitations regarding cost, clinical implementation and the need for an
      external source of sterile substitution solution to maintain fluid balance. New
      membranes that have a solute removal profile more closely approaching that of the
      glomerular filtration barrier when used for conventional haemodialysis, while at
      the same time not allowing the passage of clinically significant amounts of
      beneficial proteins, are needed to address these limitations. Tighter control of
      the molecular characteristics of the polymers used for membrane fabrication,
      along with the introduction of additives and improvements in the manufacturing
      process, has led to membranes with a tighter pore size distribution that allows
      the use of an increased absolute pore size without leaking substantial amounts of
      albumin. At the same time, the wall thickness and internal diameter of membrane
      fibres have been decreased, enhancing convective transport within the dialyser
      without the need for an external source of substitution solution. These new
      expanded range membranes provide a solute removal profile more like that of the
      native kidney than currently available membranes when used in conventional
      haemodialysis.

PMID- 30281131
TI  - Large uremic toxins: an unsolved problem in end-stage kidney disease.
AB  - Patients with end-stage kidney disease (ESKD) on maintenance hemodialysis are
      subject to a high burden of inflammation and cardiovascular disease, driven at
      least in part by retention of uremic solutes. Existing dialysis technologies
      using high-flux membranes offer limited clearance of solutes >15 kDa. New
      approaches to improve the removal of large uremic toxins include the novel medium
      cut-off dialysis membranes with pores larger than those in high-flux membranes.
      These new membranes provide the potential to improve the clearance of large
      middle molecules up to 50 kDa. In this review, we discuss 18 uremic toxins with
      molecular weights between 15 and 60 kDa that are retained in ESKD, for which
      there is evidence of a link to inflammation and/or cardiovascular disease. These
      include inflammatory proteins, cytokines, adipokines and other signaling
      proteins. Improved clearance of this group of difficult to remove molecules has
      the potential to lead to improved outcomes in dialysis patients by reducing the
      burden of cardiovascular disease, which now needs to be assessed in robust
      clinical trials.

PMID- 30281132
TI  - Cardiovascular disease in dialysis patients.
AB  - Cardiovascular disease (CVD) is a highly common complication and the first cause
      of death in patients with end-stage renal disease (ESRD) on haemodialysis (HD).
      In this population, mortality due to CVD is 20 times higher than in the general
      population and the majority of maintenance HD patients have CVD. This is likely
      due to ventricular hypertrophy as well as non-traditional risk factors, such as
      chronic volume overload, anaemia, inflammation, oxidative stress, chronic kidney
      disease-mineral bone disorder and other aspects of the 'uraemic milieu'. Better
      understanding the impact of these numerous factors on CVD would be an important
      step for prevention and treatment. In this review we focus non-traditional CVD
      risk factors in HD patients.

PMID- 30281133
TI  - From old uraemic toxins to new uraemic toxins: place of 'omics'.
AB  - Uraemic toxins seem to play an important role in the genesis of cardiovascular
      and renal damage in chronic kidney disease patients. This short article is
      divided into two thematic sections. The first part focuses on a selection of
      'old' toxins for which recent data (published between 2016 and 2018) have
      provided a better understanding of the associated harmful mechanisms and which,
      in our opinion, nephrologists should be more aware of. The second part highlights
      new perspectives for identifying and quantifying these compounds using 'omics'
      techniques.

PMID- 30281135
TI  - Erratum to: "Trophic ecology of the armadillo ant, Tatuidris tatusia, assessed by
      stable isotopes and behavioral observations".

PMID- 30281134
TI  - Expanded haemodialysis: from operational mechanism to clinical results.
AB  - Recent advances in chemical composition and new production techniques resulted in
      improved biocompatibility and permeability of dialysis membranes. Among these,
      the creation of a new class of membranes called medium cut-off (MCO) represents
      an important step towards improvement of clinical outcomes. Such membranes have
      been developed to improve the clearance of medium to high molecular weight (MW)
      solutes (i.e. uraemic toxins in the range of 5-50 kDa). MCO membranes have
      peculiar retention onset and cut-off characteristics. Due to a modified sieving
      profile, MCO membranes have also been described as high-retention onset. The
      significant internal filtration achieved in MCO haemodialysers provides a
      remarkable convective clearance of medium to high MW solutes. The marginal loss
      of albumin observed in MCO membranes compared with high cut-off membranes is
      considered acceptable, if not beneficial, producing a certain clearance of
      protein-bound solutes. The application of MCO membranes in a classic dialysis
      modality characterizes a new technique called expanded haemodialysis. This
      therapy does not need specific software or dedicated hardware, making its
      application possible in every setting where the quality of dialysis fluid meets
      current standards.

PMID- 30281136
TI  - A Case of Generalized Interstitial Granuloma Annulare and Arthritis Associated
      with Breast Cancer.

PMID- 30281137
TI  - Paraneoplastic Opsoclonus-myoclonus Syndrome Preceding a Mucosal Malignant
      Melanoma.

PMID- 30281138
TI  - A Case of Perforating Folliculitis Induced by Vemurafenib.

PMID- 30281139
TI  - Comparison of the Treatment Outcome of Oral Tofacitinib with Other Conventional
      Therapies in Refractory Alopecia Totalis and Universalis: A Retrospective Study.
AB  - Treatment of alopecia totalis and alopecia universalis is often challenging and
      unsatisfactory. Recently, Janus kinase inhibitor has shown promising results. The
      aim of this study is to compare the efficacy and tolerability of oral tofacitinib
      and conventional modalities for treating refractory alopecia totalis/universalis.
      A total of 74 patients (18 treated with tofacitinib, 26 treated with conventional
      oral treatment (steroid +/- cyclosporine), and 30 treated with
      diphenylcyclopropenone) were included in the study. The patients' medical records
      were reviewed retrospectively. After 6 months, 44.4% of patients in the
      tofacitinib group, 37.5% in the conventional oral treatment group, and 11.1% in
      the diphenylcyclopropenone group achieved 50% improvements in the Severity of
      Alopecia Tool score. During treatment, 10% of patients in the tofacitinib group,
      73.1% in the conventional oral treatment group, and 10% in the
      diphenylcyclopropenone group experienced adverse drug reactions. In conclusion,
      oral tofacitinib was more effective than diphenylcyclopropenone immunotherapy and
      more tolerable than conventional oral treatment after 6 months of treatment.

PMID- 30281140
TI  - Induced Vitiligo due to Talimogene Laherparepvec Injection for Metastatic
      Melanoma Associated with Long-term Complete Response.

PMID- 30281141
TI  - Fractional Ablative CO2 Laser Followed by Topical Application of Sodium
      Stibogluconate for Treatment of Active Cutaneous Leishmaniasis: A Randomized
      Controlled Trial.
AB  - Conventional treatment of cutaneous leishmaniasis often leaves permanent scars
      with frequent psychosocial sequelae. The aim of this study was to compare the
      efficacy, safety, associated pain and final cosmetic outcome of fractional carbon
      dioxide (CO2) laser followed by topical application of sodium stibogluconate vs.
      sodium stibogluconate injections for the treatment of cutaneous leishmaniasis. A
      total of 181 lesions (20 patients) were randomly assigned to receive
      intralesional injections of sodium stibogluconate (control group) or fractional
      CO2 laser treatment followed by topical application of sodium stibogluconate
      (study group). The visual analogue scale (VAS) score of the control group was
      much higher than that of the study group (6.85 vs. 3.5, respectively, p < 0.001).
      Both the patients and 2 blinded dermatologists found the final cosmetic outcome
      to be superior for laser-treated lesions (p = 0.001 vs. p =0.008 for controls).
      Fractional CO2 laser treatment followed by topical application of sodium
      stibogluconate is less painful and leads to a better final cosmetic outcome
      compared with intralesional injections of sodium stibogluconate.

PMID- 30281142
TI  - Ultrasound Assessment of Psoriatic Onychopathy: A Cross-sectional Study Comparing
      Psoriatic Onychopathy with Onychomycosis.
AB  - This cross-sectional study evaluated the usefulness of an ultrasound technique in
      assessment of nail changes in 35 patients with psoriatic onychopathy and 25 with
      nail dystrophy secondary to onychomycosis. All patients underwent 3 examinations:
      a complete clinical assessment; a nail ultrasound study; and fungal culture.
      Nails of patients with psoriatic onychopathy presented a thinner nail plate and
      nail bed, measured by ultrasound, than did those with onychomycosis. The
      percentage of patients with a power Doppler signal >=2 at nail bed was
      significantly higher in psoriatic onychopathy than in onychomycosis, and
      structural bone lesions were more frequent in psoriatic onychopathy than in
      onychomycosis. These results suggest that the presence of structural damage and
      high-power Doppler signal are the main ultrasound findings supporting a diagnosis
      of psoriatic onychopathy.

PMID- 30281143
TI  - Association Between Cataract and Risks of Osteoporosis and Fracture: A Nationwide
      Cohort Study.
AB  - OBJECTIVES: To evaluate the association between cataract and cataract surgery and
      risks of osteoporosis and fracture. DESIGN: Nationwide population-based
      retrospective cohort study. SETTING: Taiwan's National Health Insurance Research
      Database. PARTICIPANTS: Individuals with (n=57,972) and without (n=57,972)
      cataracts. MEASUREMENTS: Individuals with and without cataracts were matched 1:1
      for age, sex, and index year. Those with cataracts were further divided into
      cataract surgery and nonsurgery groups. Incidences and hazard ratios (HR) for
      risks of developing osteoporosis and fracture were calculated using Cox
      proportional hazard regression models. RESULTS: During mean follow-up of 6.4
      years, 17,450 participants with cataracts and 12,627 without developed
      osteoporosis or fractures. Having cataracts was significantly associated with
      risk of developing osteoporosis or fracture (adjusted HR (aHR) = 1.29, 95%
      confidence interval (CI) = 1.25-1.32, p < .001). In analyses for each event,
      cataract was significantly associated with greater likelihood of all outcomes
      (osteoporosis: aHR = 1.43, 95% CI = 1.37-1.50, p < .001; hip fracture: aHR =
      1.16, 95% CI = 1.07-1.26, p < .001; vertebral fracture: (aHR = 1.25, 95% CI =
      1.18-1.33, p < .001; other fractures: aHR = 1.24, 95% CI = 1.20-1.28, p < .001).
      Participants who underwent cataract surgery were at significantly lower risk of
      osteoporosis or fracture (aHR = 0.58, 95% CI = 0.56-0.59, p < .001), than those
      who did not. Undergoing cataract surgery was also associated with lower risks of
      all individual events (osteoporosis; hip, vertebral, other fracture). CONCLUSION:
      Cataract was independently associated with increased risks of osteoporosis and
      fracture. There might be an association between cataract surgery and lower risks
      of osteoporosis and fracture.

PMID- 30281144
TI  - Is there a burden attached to synaesthesia? Health screening of synaesthetes in
      the general population.
AB  - Synaesthesia has long been considered a benign alternative form of perception
      most often associated with positive rather than negative outcomes. The condition
      has been associated with a variety of cognitive and perceptual advantages,
      including benefits in memory, processing speed, and creativity. It is not
      currently recognized in the DSM-IV. Recently, however, several studies have
      raised the question of a possible link between synaesthesia and clinical
      conditions. Here, we present the first large-scale screening of the general
      population in which we (1) objectively identified grapheme-colour synaesthetes
      and (2) elicited information from our participants about a range of clinical
      conditions. We compared the prevalence rates of these conditions in synaesthetes
      versus non-synaesthetes to establish whether any conditions were found at a
      higher rate among synaesthetes. In our initial study, screening 3,742 people (95
      synaesthetes and 3,647 controls), we found initially that grapheme-colour was
      significantly comorbid with two conditions (anxiety disorder and obsessive
      compulsive disorder). In our second study, screening a new population of 120
      synaesthetes and 166 non-synaesthetes, we replicated our finding that grapheme
      colour synaesthesia is comorbid with anxiety disorder. At the same time, we also
      addressed a methodological concern that likely elevated rates of OCD in Study 1.
      We consider the aetiology of synaesthesia to determine whether there may be a
      shared genetic or neurological basis with anxiety disorder, and we question the
      status of synaesthesia within a mental health framework.

PMID- 30281146
TI  - Northern areas as refugia for temperate species under current climate warming:
      Atlantic salmon (Salmo salar L.) as a model in northern Europe.
AB  - In this work, patterns of geographical genetic diversity in Atlantic salmon Salmo
      salar were studied across the whole Atlantic Arc; whether these patterns (and
      thus genetic population structure) were affected by water temperatures was also
      evaluated. Salmo salar populations were characterized using microsatellite loci
      and then analysed with reference to ocean surface temperature data from across
      the region. Analysis showed the presence of a latitudinal cline of genetic
      variability (higher in northern areas) and water temperatures (sea surface
      temperatures) determining genetic population structure (the latter in combination
      with genetic drift in southern populations). Under the current global change
      scenario, northern areas of Europe would constitute refugia for diversity in the
      future. This is effectively the inverse of what appears to have happened in
      glacial refugia during the last glacial maximum. From this perspective, the still
      abundant and large northern populations S. salar should be considered as precious
      as the small almost relict southern ones and given appropriate protection.
      Careful management of the species, coordinated across countries and latitudes, is
      needed in order to avoid its extinction in Europe.

PMID- 30281147
TI  - Catch-related and genetic outcome of adult northern pike Esox lucius stocking in
      a large river system.
AB  - Genetic introgression from stocked adult northern pike Esox lucius to a wild self
      recruiting population was detected in a large river system and some stocked E.
      lucius survived up to two spawning seasons and dispersed over several kilometres
      in the river. Moreover, the catch rate of stocked E. lucius by anglers was low
      (9.6%), hence suggesting that the efficiency of stocking activity is
      questionable.

PMID- 30281145
TI  - Chemoprevention agents for melanoma: a path forward into phase 3 clinical trials.
AB  - Recent progress in the treatment of advanced melanoma has led to unprecedented
      improvements in overall survival and, as these new melanoma treatments have been
      developed and deployed in the clinic, much has been learned about the natural
      history of the disease. Now is the time to apply that knowledge toward the design
      and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention
      has the potential to reduce dramatically both the morbidity and the high costs
      associated with treating patients who have metastatic disease. In this work,
      scientific and clinical melanoma experts from the national Melanoma Prevention
      Working Group, composed of National Cancer Trials Network investigators, discuss
      research aimed at discovering and developing (or repurposing) drugs and natural
      products for the prevention of melanoma and propose an updated pipeline for
      translating the most promising agents into the clinic. The mechanism of action,
      preclinical data, epidemiological evidence, and results from available clinical
      trials are discussed for each class of compounds. Selected keratinocyte carcinoma
      chemoprevention studies also are considered, and a rationale for their inclusion
      is presented. These data are summarized in a table that lists the type and level
      of evidence available for each class of agents. Also included in the discussion
      is an assessment of additional research necessary and the likelihood that a given
      compound may be a suitable candidate for a phase 3 clinical trial within the next
      5 years.

PMID- 30281148
TI  - Progressive dissociation of cortical and subcortical network development in
      children with new-onset juvenile myoclonic epilepsy.
AB  - OBJECTIVE: Structural and functional magnetic resonance imaging (MRI) studies
      have consistently documented cortical and subcortical abnormalities in patients
      with juvenile myoclonic epilepsy (JME). However, little is known about how these
      structural abnormalities emerge from the time of epilepsy onset and how network
      interactions between and within cortical and subcortical regions may diverge in
      youth with JME compared to typically developing children. METHODS: We examined
      prospective covariations of volumetric differences derived from high-resolution
      structural MRI during the first 2 years of epilepsy diagnosis in a group of youth
      with JME (n = 21) compared to healthy controls (n = 22). We indexed developmental
      brain changes using graph theory by computing network metrics based on the
      correlation of the cortical and subcortical structural covariance near the time
      of epilepsy and 2 years later. RESULTS: Over 2 years, normally developing
      children showed modular cortical development and network integration between
      cortical and subcortical regions. In contrast, children with JME developed a
      highly correlated and less modular cortical network, which was atypically
      dissociated from subcortical structures. Furthermore, the JME group also
      presented higher clustering and lower modularity indices than controls,
      indicating weaker modules or communities. The local efficiency in JME was higher
      than controls across the majority of cortical nodes. Regarding network hubs,
      controls presented a higher number than youth with JME that were spread across
      the brain with ample representation from the different modules. In contrast,
      children with JME showed a lower number of hubs that were mainly from one module
      and comprised mostly subcortical structures. SIGNIFICANCE: Youth with JME
      prospectively developed a network of highly correlated cortical regions
      dissociated from subcortical structures during the first 2 years after epilepsy
      onset. The cortical-subcortical network dissociation provides converging insights
      into the disparate literature of cortical and subcortical abnormalities found in
      previous studies.

PMID- 30281149
TI  - Genomic and transcriptomic characterisation of undifferentiated pleomorphic
      sarcoma of bone.
AB  - Undifferentiated pleomorphic sarcoma of bone (UPSb), is a rare primary bone
      sarcoma that lacks a specific line of differentiation. There is very little
      information about the genetic alterations leading to tumourigenesis or malignant
      transformation. Distinguishing between UPSb and other malignant bone sarcomas,
      including dedifferentiated chondrosarcoma and osteosarcoma, can be challenging
      due to overlapping features. To explore the genomic and transcriptomic landscape
      of UPSb tumours, whole-exome sequencing (WES) and RNA Sequencing (RNA-Seq) were
      performed on UPSb tumours. All tumours lacked hotspot mutations in IDH1/2 132 or
      172 codons, thereby excluding the diagnosis of dedifferentiated chondrosarcoma.
      Recurrent somatic mutations in TP53 were identified in 4/14 samples (29%).
      Moreover, recurrent mutations in histone chromatin remodelling genes, including
      H3F3A, ATRX and DOT1L, were identified in 5/14 samples (36%), highlighting the
      potential role of deregulated chromatin remodelling pathways in UPSb
      tumourigenesis. The majority of recurrent mutations in chromatin remodelling
      genes identified here are reported in COSMIC, including the H3F3A G35 and K36
      hotspot residues. Copy number alteration analysis identified gains and losses in
      genes that have been previously altered in UPSb or UPS of soft tissue. Eight
      somatic gene fusions were identified by RNA-Seq, two of which, CLTC-VMP1 and
      FARP1-STK24, were reported previously in multiple cancers. Five gene fusions were
      genomically characterised. Hierarchical clustering analysis, using RNA-Seq data,
      distinctly clustered UPSb tumours from osteosarcoma and other sarcomas, thus
      molecularly distinguishing UPSb from other sarcomas. RNA-Seq expression profiling
      analysis and quantitative RT-PCR showed an elevated expression in FGF23 which can
      be a potential molecular biomarker in UPSb. To our knowledge, this study
      represents the first comprehensive WES and RNA-Seq analysis of UPSb tumours
      revealing novel protein-coding recurrent gene mutations, gene fusions and
      identifying a potential UPSb molecular biomarker, thereby broadening the
      understanding of the pathogenic mechanisms and highlighting the possibility of
      developing novel targeted therapeutics.

PMID- 30281150
TI  - Increased sensitivity of the circadian system to light in delayed sleep-wake
      phase disorder.
AB  - KEY POINTS: This is the first study to demonstrate an altered circadian phase
      shifting response in a circadian rhythm sleep disorder. Patients with delayed
      sleep-wake phase disorder (DSWPD) demonstrate greater sensitivity of the
      circadian system to the phase-delaying effects of light. Increased circadian
      sensitivity to light is associated with later circadian timing within both
      control and DSWPD groups. DSWPD patients had a greater sustained pupil response
      after light exposure. Treatments for DSWPD should consider sensitivity of the
      circadian system to light as a potential underlying vulnerability, making
      patients susceptible to relapse. ABSTRACT: Patients with delayed sleep-wake phase
      disorder (DSWPD) exhibit delayed sleep-wake behaviour relative to desired
      bedtime, often leading to chronic sleep restriction and daytime dysfunction. The
      majority of DSWPD patients also display delayed circadian timing in the melatonin
      rhythm. Hypersensitivity of the circadian system to phase-delaying light is a
      plausible physiological basis for DSWPD vulnerability. We compared the phase
      shifting response to a 6.5 h light exposure (~150 lux) between male patients with
      diagnosed DSWPD (n = 10; aged 20.8 +/- 2.3 years) and male healthy controls (n =
      11; aged 22.4 +/- 3.3 years). Salivary dim light melatonin onset (DLMO) was
      measured under controlled conditions in dim light (<3 lux) before and after light
      exposure. Correcting for the circadian time of the light exposure, DSWPD patients
      exhibited 31.5% greater phase delay shifts than healthy controls. In both groups,
      a later initial melatonin phase was associated with a greater magnitude phase
      shift, indicating that increased circadian sensitivity to light may be a factor
      that contributes to delayed phase, even in non-clinical groups. DSWPD patients
      also had reduced pupil size following the light exposure, and showed a trend
      towards increased melatonin suppression during light exposure. These findings
      indicate that, for patients with DSWPD, assessment of light sensitivity may be an
      important factor that can inform behavioural therapy, including minimization of
      exposure to phase-delaying night-time light.

PMID- 30281151
TI  - Gastrointestinal effects following acupuncture at Pericardium-6 and Stomach-36 in
      healthy dogs: a pilot study.
AB  - OBJECTIVES: To quantify changes in gastric and intestinal emptying times in the
      conscious dog following gastrointestinal acupoint stimulation. MATERIALS AND
      METHODS: In a randomised, blinded crossover study, six dogs were fed 30*1.5 mm
      barium-impregnated polyethylene spheres and underwent: (1) no acupuncture
      (Control); (2) stimulation of target points PC6 and ST36 (Target) and (3)
      stimulation of non-target points LU7 and BL55 (Sham). Abdominal radiographs were
      assessed immediately after feeding the spheres and every hour for 12 hours and
      their number in the stomach and large intestines was counted. RESULTS: The number
      of barium-impregnated polyethylene spheres found distal to the stomach was less
      in the Target group compared to the Control and Sham groups between hours 2 and
      4, but no differences between groups were seen for the remainder of the treatment
      period. The number of spheres found within the colon/rectum was less in the
      Target group compared to the Control and Sham groups between hours 4 and 6, and
      compared to the Sham group only at hour 7 but no differences between groups were
      seen after hour 8. CLINICAL SIGNIFICANCE: Acupuncture targeted at the
      gastrointestinal tract of dogs was associated briefly with slowed gastric
      emptying and gastrointestinal transit time. This foundational study lays the
      groundwork for additional studies of acupuncture effects associated with altered
      physiologic states.

PMID- 30281152
TI  - QRICH1 mutations cause a chondrodysplasia with developmental delay.
AB  - In many children with short stature, the etiology of the decreased linear growth
      remains unknown. We sought to identify the underlying genetic etiology in a
      patient with short stature, irregular growth plates of the proximal phalanges,
      developmental delay, and mildly dysmorphic facial features. Exome sequencing
      identified a de novo, heterozygous, nonsense mutation (c.1606C>T:p.R536X) in
      QRICH1. In vitro studies confirmed that the mutation impaired expression of the
      QRICH1 protein. SiRNA-mediated knockdown of Qrich1 in primary mouse epiphyseal
      chondrocytes caused downregulation of gene expression associated with
      hypertrophic differentiation. We then identified an unrelated individual with
      another heterozygous de novo nonsense mutation in QRICH1 who had a similar
      phenotype. A recently published study identified QRICH1 mutations in three
      patients with developmental delay, one of whom had short stature. Our findings
      indicate that QRICH1 mutations cause not only developmental delay but also a
      chondrodysplasia characterized by diminished linear growth and abnormal growth
      plate morphology due to impaired growth plate chondrocyte hypertrophic
      differentiation.

PMID- 30281153
TI  - Sex differences in adolescent physical aggression: Evidence from sixty-three low
      and middle-income countries.
AB  - A great deal of research shows that adolescent and adult males are more likely to
      engage in physical aggression and violence than females are. However, few studies
      have examined cross-cultural variation in sex differences, particularly among low
      and middle-income countries [LMICs]. Based on social role and sexual selection
      theories, we derived two hypotheses regarding possible variations in sex
      differences across societal contexts: 1) sex differences increase with societal
      gender polarization (social role theory) and 2) sex differences are exacerbated
      in societies where socio-economic opportunities are scarce, unequal, or insecure
      (prediction derived from sexual selection theory). The current study examined the
      prevalence of and variation in sex differences in physical aggression, as
      measured by frequent fighting, among 247,909 adolescents in 63 low- and middle
      income countries. The results show that, overall, males were over twice as likely
      (OR = 2.68; 95% CI = 2.60-2.76) to report frequent fighting in the past 12 months
      than females. However, sex differences vary significantly across LMICs, wherein
      countries with higher female prevalence rates have smaller sex differences in
      frequent fighting. Contrary to expectations derived from social role theory, sex
      differences in physical aggression decrease as societal gender inequality
      increased. In regards to sexual selection theory, we find no evidence that sex
      differences in frequent fighting varies according to societal rule of law or
      income inequality.

PMID- 30281154
TI  - miR-191 modulates B-cell development and targets transcription factors E2A,
      Foxp1, and Egr1.
AB  - The interdependence of posttranscriptional gene regulation via miRNA and
      transcriptional regulatory networks in lymphocyte development is poorly
      understood. Here, we identified miR-191 as direct upstream modulator of a
      transcriptional module comprising the transcription factors Foxp1, E2A, and Egr1.
      Deletion as well as ectopic expression of miR-191 resulted in developmental
      arrest in B lineage cells, indicating that fine tuning of the combined expression
      levels of Foxp1, E2A, and Egr1, which in turn control somatic recombination and
      cytokine-driven expansion, constitutes a prerequisite for efficient B-cell
      development. In conclusion, we propose that miR-191 acts as a rheostat in B-cell
      development by fine tuning a key transcriptional program.

PMID- 30281155
TI  - MYC-driven malignant transformation of mature murine B cells requires inhibition
      of both intrinsic apoptosis and p53 activity.
AB  - Increased expression of the oncogene MYC is a common feature of many B-cell
      malignancies, however MYC overexpression by itself is not sufficient for
      transformation, and additional genetic events are required, although the exact
      nature of these remains unknown. In patients and in transgenic mouse models,
      oncogenic transformation may occur in B cells at various differentiation stages
      interacting with complex microenvironments. B-cell oncogenesis often occurs after
      prolonged periods of time, making it difficult to accurately identify the genetic
      events required for transformation. An in vitro system, where malignant
      transformation of primary B cells could be analyzed, would facilitate the
      identification of genetic events required for transformation. Here, we describe
      such a system and show that primary murine B cells rapidly become transformed
      upon forced expression of MYC, in conjunction with simultaneous inhibition of the
      ARF/p53 axis via overexpression of BMI1, as well as through downregulation of
      p19ARF or expression of a dominant-negative p53 and suppression of intrinsic
      apoptosis through overexpression of BCLXL or MCL1. Established tumor cells
      remained addicted to expression of the lymphoma-inducing genes. In mice,
      transformed cells rapidly established fatal B-cell lymphomas. Our results suggest
      that transformation of normal mature B cells into lymphomas can occur as a
      consequence of three defined events.

PMID- 30281156
TI  - Cryopreservation of buffy coat-derived platelet concentrates photochemically
      treated with amotosalen and UVA light.
AB  - BACKGROUND: Cryopreserved platelets (CPPs) are considered a promising approach
      for extended platelet storage, bridging inventory shortages of conventionally
      stored platelets. It is unknown if platelet concentrates exposed to photochemical
      treatment (PCT) with amotosalen and ultraviolet A (UVA) light, to inactivate
      pathogens, are suitable for freezing. The objective of this study was to analyze
      potential effects of PCT on CPPs as compared with untreated CPPs. STUDY DESIGN
      AND METHODS: A total of 12 PCT-treated and 12 untreated platelet units from buffy
      coats were cryopreserved at -80 degrees C in 5% dimethyl sulfoxide. CPPs of both
      types were rapidly thawed at 37 degrees C and resuspended in 200 mL fresh plasma.
      In vitro properties were analyzed prefreezing, postfreezing and thawing, and on
      Day 1 after thawing. RESULTS: Directly after thawing, no major differences in
      platelet content, lactase hydrogenase, adenosine triphosphate, mitochondrial
      membrane potential, CD62P, CD42b, and platelet endothelial cell adhesion molecule
      were seen between PCT-CPPs and conventional CPPs. Agonist-induced PAC-1
      expression and contribution of CPPs to blood coagulation in an experimental
      rotational thromboelastometry setup were also similar between the groups. On Day
      1 after thawing, the CPPs of both types performed less well. The PCT-CPPs tended
      to be more affected by the freezing process than the conventional CPPs.
      CONCLUSIONS: PCT-CPPs appeared slightly more susceptible to lesion effects by
      freezing than conventional CPPs, in particular in assays on Day 1 after thawing,
      but these differences were small relative to the dramatic effects of the freezing
      process itself.

PMID- 30281157
TI  - Stronger effects of heterozygosity on survival in harsher environments.
AB  - The hypothesis that the effects of heterozygosity vary with environmental
      conditions was tested using six populations of marble trout Salmo marmoratus from
      western Slovenia as a model system. The hypotheses tested were: stronger effects
      of heterozygosity on survival in populations characterized by low average
      survival; no effects of heterozygosity on probability of surviving flash floods
      owing to their largely non-selective effects across traits; stronger effects of
      heterozygosity on survival for fish born after floods than fish born before. A
      significant effect of heterozygosity on survival was found in populations
      characterized by low average survival. There were no effects of heterozygosity on
      probability of surviving flash floods, but in one population a positive
      correlation between heterozygosity and survival for fish born after the extreme
      events was found, probably because crowding in a small section of the stream
      caused more intense competition for resources.

PMID- 30281158
TI  - Changes in gene and genotype frequencies during the development of the grass carp
      Ctenopharyngodon idella.
AB  - In this study, a full-sib population of Ctenopharyngodon idella was constructed
      and approximately 500 C. idella individuals were sampled at four early
      developmental stages (hatching, first feeding, juvenile fish and young fish).
      Four DNA pools were constructed and subjected to next-generation sequencing. On
      the basis of the identification of single nucleotide polymorphisms (SNP), changes
      in gene and genotype frequencies during the developmental progress of C. idella
      were revealed, which indicates that death during the early developmental stage is
      not a random process. These findings will establish the basis for further studies
      performed for identifying superior alleles or genotypes as target markers for
      molecular breeding.

PMID- 30281159
TI  - Seasonal aggregation and diel activity by the sicklefin devil ray Mobula
      tarapacana off a small, equatorial outcrop of the Mid-Atlantic Ridge.
AB  - The present study aimed to analyse occurrence patterns, relative abundance and
      habitat use by the sicklefin devil ray Mobula tarapacana in the Saint Peter and
      Saint Paul Archipelago (SPSPA), Brazil, located in the Mid-Atlantic Ridge.
      Sampling was conducted between December 2008 and December 2012 by surface surveys
      and tagging with conventional tags and acoustic transmitters. Mobula tarapacana
      were sighted in the SPSPA year round but the highest frequency of occurrence was
      observed from January to June, probably due to greater food availability during
      this season. However, M. tarapacana might also use the area for reproductive
      purposes based on evidence of mating behaviour. The residency period of tagged
      rays measured by three autonomous acoustic receivers deployed around SPSPA
      spanned from 1 to 74 days with most of the detections occurring during daytime.
      These results suggest that the SPSPA could be an ecologically-important
      aggregation area for M. tarapacana, possibly providing the species with a feeding
      or resting habitat while transiting in the equatorial Atlantic Ocean.

PMID- 30281160
TI  - Vacuum-driven fluid manipulation by a piezoelectric diaphragm micropump for
      microfluidic droplet generation with a rapid system response time.
AB  - Recently, we developed a convenient microfluidic droplet generation device based
      on vacuum-driven fluid manipulation with a piezoelectric diaphragm micropump. In
      the present study built on our previous work, we investigate the influence of
      settings applied to the piezoelectric pump, such as peak-to-peak drive voltage
      (Vp-p ) and wave frequency, on droplet generation characteristics. Stepwise
      adjustments to the drive voltage in +/-10-Vp-p increments over the range of 200
      250 Vp-p during droplet creation revealed that the droplet generation rate could
      be reproducibly controlled at a specific drive voltage. The droplet generation
      rate switched within <0.5 s after the input of a new voltage. Although the
      droplet generation rate depended on the drive voltage, this setting had almost no
      influence on droplet size. The frequency over the selected range (50-60 Hz) did
      not markedly influence the droplet generation rate or droplet size. We show that
      the current fluid manipulation system can be conveniently used for both droplet
      generation and for rapid droplet reading, which is required in many microfluidic
      based applications.

PMID- 30281162
TI  - Requirements and Pitfalls of Dialyzer Sieving Coefficients Comparisons.
AB  - Sieving coefficients reported in dialyzer data sheets and instructions for use
      (IFUs) indicate the potential of different solutes to pass across a particular
      membrane. Despite being measured in vitro, sieving coefficient data are often
      used as a predictor of the clinical performance of dialyzers. Although standards
      for the measurement of sieving coefficients exist, the stated methodologies do
      not offer sufficient guidance to ensure comparability of test results between
      different dialyzers. The aim of this work was to investigate the relationship
      between sieving coefficients and published clinical performance indicators for
      two solutes, albumin loss and beta-2 microglobulin (beta2 M) reduction ratio
      (RR), and to assess the impact of different in vitro test parameters on sieving
      coefficient values for albumin, beta2 M, and myoglobin. Clinical albumin loss and
      beta2 M RR for commercially available dialyzers used in hemodialysis (HD) and
      post-dilution hemodiafiltration (HDF) were extracted from the literature and
      plotted against sieving coefficients reported in data sheets and IFUs. Albumin,
      beta2 M, and myoglobin sieving coefficients of a selection of dialyzers were
      measured per the ISO 8637 standard. The impact of in vitro testing conditions was
      assessed by changing blood flow rate, ultrafiltration (UF) rate, sampling time,
      and origin of test plasma. Results showed variation in albumin loss and beta2 M
      RR for the same sieving coefficient across different dialyzers in HD and HDF.
      Changes in blood flow rates, UF rates, sampling time, and test plasma (bovine vs.
      human) caused marked differences in sieving coefficient values for all
      investigated solutes. When identical testing conditions were used, sieving
      coefficient values for the same dialyzer were reproducible. Testing conditions
      have a marked impact on the measurement of sieving coefficients, and values
      should not be compared unless identical conditions are used. Further, variability
      in observed clinical data in part reflects the lack of definition of test
      conditions.

PMID- 30281163
TI  - Vacuum-Assisted Closure for Mediastinitis in Pediatric Cardiac Surgery: A Single
      Center Experience.
AB  - Vacuum-assisted closure (VAC) has been widely used to treat mediastinitis after
      congenital cardiac surgery, which is associated with a high risk of morbidity and
      mortality. The aim in this study is to review our 14 cases of mediastinitis
      treated with VAC therapy after congenital cardiac surgery. We retrospectively
      reviewed the medical records of 14 congenital heart patients with mediastinitis
      from January 2012 to March 2017. Patients with fever, wound discharge, sternal
      dehiscence, a positive wound culture or abscess diagnosed with computed
      tomography are accepted as mediastinitis. A VAC was applied to all our patients
      without irrigation or dressing the wound because of sterility concerns. The
      vacuuming of the wound was either 50 mm Hg or 75 mm Hg according to the sternal
      intactness. We gradually decreased the pressures and changed the VAC systems once
      every three days, after wound healing was seen and a negative culture was
      obtained and VAC was terminated. There were 14 patients (8 male and 6 female)
      with mediastinitis and all of them were treated using VAC. The mean age of the
      patients was 6.96 months (ranging from 0.5-26 months). The mean weight was 5.16
      kg (2.8-12 kg). Three patients needed extracorporeal membrane oxygenation after
      the surgery. Mean onset of mediastinitis was 25.3 days. The wound cultures showed
      methicillin resistant coagulase negative streptococcus and methicillin-sensitive
      staphylococcus aureus in most cases. Acinetobacter, serratia, pseudomonas, and
      klebsiella were the other bacterial species seen in cultures. Two patients had
      mediastinitis symptoms, but their cultures were negative. VAC systems were
      changed 3.85 times on average. Mean duration of hospital stay was 49.9 days (21
      104 days). One patient needed a muscle flap to close the thoracic cavity after
      mediastinitis. Two patients did not survive. Mediastinitis is a serious
      postoperative condition in pediatric cardiac surgery patients. Classical wound
      dressing and irrigation methods are not suitable in mediastinitis for the
      pediatric age group. Therefore, VAC therapy can be an effective way to
      successfully treat the situation.

PMID- 30281161
TI  - Daily Drinking Is Associated with Increased Mortality.
AB  - BACKGROUND: There is evidence that low-level alcohol use, drinking 1 to 2 drinks
      on occasion, is protective for cardiovascular disease, but increases the risk of
      cancer. Synthesizing the overall impact of low-level alcohol use on health is
      therefore complex. The objective of this paper was to examine the association
      between frequency of low-level drinking and mortality. METHODS: Two data sets
      with self-reported alcohol use and mortality follow-up were analyzed: 340,668
      individuals from the National Health Interview Survey (NHIS) and 93,653
      individuals from the Veterans Health Administration (VA) outpatient medical
      records. Survival analyses were conducted to evaluate the association between low
      level drinking frequency and mortality. RESULTS: The minimum risk drinking
      frequency among those who drink 1 to 2 drinks per occasion was found to be 3.2
      times weekly in the NHIS data, based on a continuous measure of drinking
      frequency, and 2 to 3 times weekly in the VA data. Relative to these individuals
      with minimum risk, individuals who drink 7 times weekly had an adjusted hazard
      ratio (HR) of all-cause mortality of 1.23 (p < 0.0001) in the NHIS data, and
      individuals who drink 4 to 7 times weekly in the VA data also had an adjusted HR
      of 1.23 (p = 0.01). Secondary analyses in the NHIS data showed that the minimum
      risk was drinking 4 times weekly for cardiovascular mortality, and drinking
      monthly or less for cancer mortality. The associations were consistent in
      stratified analyses of men, women, and never smokers. CONCLUSIONS: The minimum
      risk of low-level drinking frequency for all-cause mortality appears to be
      approximately 3 occasions weekly. The robustness of this finding is highlighted
      in 2 distinctly different data sets: a large epidemiological data set and a data
      set of veterans sampled from an outpatient clinic. Daily drinking, even at low
      levels, is detrimental to one's health.

PMID- 30281164
TI  - To accept or not to accept: Level of moral concern impacts on tolerance of Muslim
      minority practices.
AB  - Living with diversity requires that we sometimes accept outgroup practices that
      we personally disapprove of (i.e., tolerance). Using an experimental design, we
      examined Dutch majority group members' tolerance of controversial practices with
      varying degrees of moral concern, performed by a culturally dissimilar (Muslims)
      or similar (orthodox Protestant) minority group. Furthermore, we examined whether
      arguments in favour or against (or a combination of both) the specific practice
      impacted tolerance. Results indicated that participants expressed less tolerance
      for provocative practices when it was associated with Muslims than orthodox
      Protestants, but not when such practices elicit high degrees of moral concern.
      This indicates that opposition towards specific practices is not just a question
      of dislike of Muslims, but can involve disapproval of specific practices.
      Argument framing did not have a consistent effect on the level of tolerance for
      the practices.

PMID- 30281165
TI  - Design and monitoring of survival trials in complex scenarios.
AB  - This paper proposes an approach to design and monitor survival trials accounting
      for complex scenarios such as delayed treatment effect, treatment dilution, and
      treatment crossover. These scenarios often lead to non-proportional hazards,
      making study design and monitoring more difficult. We demonstrate that, with
      event times following piecewise exponential distributions, the log-rank statistic
      as well as its variance-covariance structure can be easily computed, which
      greatly simplifies study design and monitoring. As the number of pieces in the
      exponential distributions can be arbitrary, this approach can handle a wide range
      of scenarios. Three hypothetical examples are used to demonstrate its potential
      use.

PMID- 30281166
TI  - Ultrasound imaging of the superior cluneal nerve: Sonoanatomy of the osteo
      fibrous tunnel revisited.

PMID- 30281167
TI  - Psychological impact of different primary treatments for prostate cancer: A
      critical analysis.
AB  - Limited attention has been given to the psychological impact of primary
      treatments in patients with prostate cancer. Aim of our analysis was to
      critically analyse the current evidence on the psychological impact of different
      primary treatments (surgery, radiotherapy and active surveillance), in patients
      with prostate cancer, using validated questionnaires. We searched in the MEDLINE
      and Cochrane library database from the literature of the past 15 years (primary
      fields: prostate neoplasm, AND radical prostatectomy or radiotherapy or active
      surveillance AND psychological distress or anxiety or depression; secondary
      fields: urinary, sexual, bowel modifications, non-randomised and randomised
      trials). Overall eighteen original and review articles were included and
      critically evaluated. Either radical prostatectomy or active surveillance and
      radiotherapy are well-tolerated in terms of definite anxiety and depression
      during the post-treatment follow-up. A mutual influence between functional and
      psychological modifications induced by treatments has been demonstrated. Urinary
      symptoms related to incontinence more than sexual and bowel dysfunction are able
      to induce psychological distress worsening. In conclusion, patients and their
      clinicians might wish to know how functional and psychological aspects may
      differently be influenced by treatment choice.

PMID- 30281168
TI  - Integration of anatomical and radiological analysis suggests more segments in the
      human kidney.
AB  - An increasing number of observations have called the general scheme of five renal
      segments into question: anatomists, radiologists, and surgeons have reported
      discrepancies between Graves's scheme and morphological observations. The aims of
      the present study are: (1) to assess the correspondence between a virtual and a
      real vascular cast of the kidney; (2) to analyze the arterial anatomy with
      reference to the renal segments. Fifteen kidneys were injected with acrylic
      resins to obtain vascular casts, which were also analyzed by computed tomography.
      A mean of 6.3 (range 4-8) avascular fissures was found, indicating a mean of 7.3
      segments (range 5-9). In the superior and middle territories there was a single
      segment in 4 (26.7%) and 8 (53.3%) cases, respectively, and there were two
      segments in 11 (73.3%) and in 7 (46.7%) cases, respectively. In the inferior
      territory there was a single segment in two cases (13.3%), two segments in nine
      (60%), and three segments in four (26.7%). A mean segmental volume of 550.5 mm3
      was calculated; the posterior (1,030.1 mm3 , 28.9%) and inferior (450.3 mm3 ,
      24.2%) segments were the largest. More third order branches were identified in
      the inferior segments than in the other segments (three branches of the inferior
      segmental artery in 26.6%). According to these data the inferior segment occupies
      the inferior pole, extending both anteriorly and posteriorly. In conclusion, the
      high correspondence between a virtual and a real vascular cast permits more
      segments to be identified than those described by Graves, and the volume of each
      segment can be calculated. Clin. Anat., 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30281169
TI  - Systematic High-Accuracy Prediction of Electron Affinities for Biological
      Quinones.
AB  - Quinones play vital roles as electron carriers in fundamental biological
      processes; therefore, the ability to accurately predict their electron affinities
      is crucial for understanding their properties and function. The increasing
      availability of cost-effective implementations of correlated wave function
      methods for both closed-shell and open-shell systems offers an alternative to
      density functional theory approaches that have traditionally dominated the field
      despite their shortcomings. Here, we define a benchmark set of quinones with
      experimentally available electron affinities and evaluate a range of electronic
      structure methods, setting a target accuracy of 0.1 eV. Among wave function
      methods, we test various implementations of coupled cluster (CC) theory,
      including local pair natural orbital (LPNO) approaches to canonical and
      parameterized CCSD, the domain-based DLPNO approximation, and the equations-of
      motion approach for electron affinities, EA-EOM-CCSD. In addition, several
      variants of canonical, spin-component-scaled, orbital-optimized, and explicitly
      correlated (F12) Moller-Plesset perturbation theory are benchmarked. Achieving
      systematically the target level of accuracy is challenging and a composite scheme
      that combines canonical CCSD(T) with large basis set LPNO-based extrapolation of
      correlation energy proves to be the most accurate approach. Methods that offer
      comparable performance are the parameterized LPNO-pCCSD, the DLPNO-CCSD(T0 ), and
      the orbital optimized OO-SCS-MP2. Among DFT methods, viable practical
      alternatives are only the M06 and the double hybrids, but the latter should be
      employed with caution because of significant basis set sensitivity. A highly
      accurate yet cost-effective DLPNO-based coupled cluster approach is used to
      investigate the methoxy conformation effect on the electron affinities of
      ubiquinones found in photosynthetic bacterial reaction centers. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30281170
TI  - Effects of maturation and size on population pharmacokinetics of pentoxifylline
      and its metabolites in very preterm infants with suspected late-onset sepsis or
      necrotizing enterocolitis: a pilot study incorporating clinical outcomes.
AB  - AIMS: Infection-induced inflammation is associated with adverse long-term
      outcomes in preterm infants. Pentoxifylline (PTX) is a candidate for adjunct
      immunomodulatory therapy in preterm infants with late-onset sepsis (LOS) and
      necrotizing enterocolitis (NEC), but pharmacokinetic data in this population are
      extremely limited. This study aims to characterize the pharmacokinetic properties
      of intravenous PTX and its metabolites in preterm infants. METHOD: An open label
      pilot clinical study of intravenous PTX as an adjunct therapy in preterm infants
      (gestation <32 weeks) with suspected LOS or NEC was undertaken. PTX was infused
      for 12 h for two days (60 mg kg-1 per 12 h), and in infants with confirmed
      diagnosis of LOS or NEC, for 6 h for another 4 days (30 mg kg-1 per 6 h). Plasma
      concentrations of PTX and its principal metabolites from collected blood samples
      were measured using a validated LCMS assay. NONMEM was used to analyse the data
      using population pharmacokinetic modelling. RESULTS: The preterm infants (n = 26)
      had a median (range) gestation of 24.8 weeks (23.3-30.4) and birthweight of 689 g
      (370-1285). PTX was well tolerated and without treatment-limiting adverse
      effects. Changes in size (weight) and maturation were successfully modelled for
      PTX and metabolites. After allometric scaling, clearance increased with
      postmenstrual age, increasing by approximately 30% per week for PTX and M1
      (lisofylline) and simulations of current dosing demonstrated a six-fold
      difference in exposure between 24 and 35 weeks postmenstrual age. CONCLUSIONS:
      The developed model can be used to explore dosing strategies based on size and
      maturation for preterm infants.

PMID- 30281171
TI  - Recombinant human BMP9 (RhBMP9) in comparison with rhBMP2 for ridge augmentation
      following tooth extraction: An experimental study in the Beagle dog.
AB  - OBJECTIVES: The purpose of this study was to compare the effects of rhBMP2 with
      rhBMP9 on ridge augmentation following healing of extraction sockets in dogs.
      MATERIAL AND METHODS: Five male Beagle dogs, approximately 12 months of age, were
      used. The mesial roots of the four maxillary premolars were endodontically
      treated. The distal roots were extracted, and the buccal bony walls removed. All
      extraction sockets were filled with deproteinized bovine bone mineral (DBBM). A
      collagen membrane was soaked with 4 MUg or 20 MUg of rhBMP9, 20 MUg of rhBMP2 or
      sterile saline and placed over the augmented sites. All animals were euthanized
      after 8 weeks of healing and investigated by micro-CT and histologic analysis. A
      one-way ANOVA with Tukey's HSD post hoc test was used to compare the differences
      between the four groups. RESULTS: New bone apposition in all defects was observed
      from the original bone. RhBMP samples showed an increase in bone formation in the
      buccal area and better integration of DBBM particles when compared to control
      sites. Both rhBMP9 defects showed higher values of bone (p = 0.024), bone marrow
      (p = 0.044), and total augmentation volume (p = 0.033) than the rhBMP2 (20 MUg)
      or control sites. Highest bone area was found in rhBMP9 defects (p = 0.895).
      CONCLUSIONS: Within the limitations of the present study, rhBMP9 sites
      demonstrated higher bone-inducing potential in combination with DBBM than rhBMP2.
      While rhBMP9s failed to demonstrate a clear dose-response relationship to the
      outcomes, future studies are necessary to evaluate the appropriate dose and
      carrier systems.

PMID- 30281172
TI  - A Self-Portrait of Michelangelo Buonarroti Hidden in a Drawing from the Ashmolean
      Museum.
AB  - The discovery was recently announced in the scientific literature of a self
      caricature of the great Renaissance artist and genius of human anatomy,
      Michelangelo Buonarroti (1475-1564), concealed in a drawing from 1525. This
      drawing is held in the collection of the British Museum in London, England. In
      it, the artist portrayed the Marchesa di Pescara, Vittoria Colonna (1490-1547).
      The present article considers evidence that Michelangelo may have depicted
      himself in another portrait of Vittoria Colonna, dated to approximately 1522,
      which is currently in the collection of the Ashmolean Museum in Oxford, England.
      This concealed silhouetted figure displays physical features strikingly similar
      to those depicted in portraits of Michelangelo by his contemporaries, and in the
      description of the artist by Michelangelo's biographer, Giorgio Vasari (1511
      1574): the large body, the shape of the face, the beard and the flattened nose.
      In this context, the present article could serve to facilitate analyses of the
      physical form and even of the state of health (from 1522) of one of the foremost
      anatomists of the Renaissance. Clin. Anat., 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 30281173
TI  - A Nano-Sized [MnII 18 ] Metallamacrocycle as a Building Unit to Construct Stable
      Metal-Organic Frameworks: Effective Gas Adsorption and Magnetic Properties.
AB  - A stable hex-type metal-organic framework (MOF, WMOF-1) was constructed by nano
      sized [MnII 18 ] metallamacrocycle secondary building unit, being the one with
      the highest nuclearity of manganese wheel-like node in the microporous MOF. WMOF
      1 displays an effective gas adsorption and the antiferromagnetic behavior.

PMID- 30281174
TI  - Licochalcone A attenuates acne symptoms mediated by suppression of NLRP3
      inflammasome.
AB  - Activation of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3)
      inflammasome by Propionibacterium acnes (P. acnes) is critical for inducing
      inflammation and aggravating the development of acne lesions. We searched for
      available small-molecule inhibitors of the NLRP3 inflammasome that could be
      topically administered for the treatment of acne. We found that licochalcone A, a
      chalconoid isolated from the root of Glycyrrhiza inflate, was an effective
      inhibitor for P. acnes-induced NLRP3 inflammasome activation. Licochalcone A
      blocked P. acnes-induced production of caspase-1(p10) and IL-1beta in primary
      mouse macrophages and human SZ95 sebocytes, indicating the suppression of NLRP3
      inflammasome. Licochalcone A suppressed P. acnes-induced ASC speck formation and
      mitochondrial reactive oxygen species. Topical application of licochalcone A to
      mouse ear skin attenuated P. acnes-induced skin inflammation as shown by
      histological assessment, ear thickness measurement, and inflammatory gene
      expression. Licochalcone A reduced caspase-1 activity and IL-1beta production in
      mouse ear injected with P. acnes. This study demonstrated that licochalcone A is
      effective in the control of P. acnes-induced skin inflammation as an efficient
      inhibitor for NLRP3 inflammasome. Our study provides a new paradigm for the
      development of anti-acne therapy via targeting NLRP3 inflammasome.

PMID- 30281175
TI  - A systematic review on the neuroprotective perspectives of beta-caryophyllene.
AB  - Beta (beta)-caryophyllene (BCAR) is a major sesquiterpene of various plant
      essential oils reported for several important pharmacological activities,
      including antioxidant, anti-inflammatory, anticancer, cardioprotective,
      hepatoprotective, gastroprotective, nephroprotective, antimicrobial, and immune
      modulatory activity. Recent studies suggest that it also possesses
      neuroprotective effect. This study reviews published reports pertaining to the
      neuropharmacological activities of BCAR. Databases such as PubMed, Scopus,
      MedLine Plus, and Google Scholar with keywords "beta (beta)-caryophyllene" and
      other neurological keywords were searched. Data were extracted by referring to
      articles with information about the dose or concentration/route of
      administration, test system, results and discussion, and proposed mechanism of
      action. A total of 545 research articles were recorded, and 41 experimental
      studies were included in this review, after application of exclusion criterion.
      Search results suggest that BCAR exhibits a protective role in a number of
      nervous system-related disorders including pain, anxiety, spasm, convulsion,
      depression, alcoholism, and Alzheimer's disease. Additionally, BCAR has local
      anesthetic-like activity, which could protect the nervous system from oxidative
      stress and inflammation and can act as an immunomodulatory agent. Most
      neurological activities of this natural product have been linked with the
      cannabinoid receptors (CBRs), especially the CB2R. This review suggests a
      possible application of BCAR as a neuroprotective agent.

PMID- 30281176
TI  - Flavonoid-rich fraction of Bauhinia forficata Link leaves prevents the intestinal
      toxic effects of irinotecan chemotherapy in IEC-6 cells and in mice.
AB  - This study evaluated the effects of flavonoid-rich fraction from Bauhinia
      forficata leaves (FRF-BF), against intestinal toxicity induced by irinotecan. The
      leaves of this plant are used like tea in Brazilian folk medicine, and it is rich
      in flavonoids, mainly kaempferitrin. First, the chemopreventive effects of FRF-BF
      and kaempferitrin were evaluated in intestinal cells (IEC-6 cells) exposed to
      irinotecan. Next, the effects were evaluated against irinotecan-induced mucositis
      in mice. Lastly, melanoma was induced in C57BL/6 mice to evaluate FRF-BF
      interference on irinotecan antitumor activity. The results showed that FRF-BF and
      kaempferitrin exert no cytotoxic effects in IEC-6 cells and confirmed that
      pretreatment with FRF-BF and kaempferitrin displays chemoprotective effects
      against cytotoxicity induced by irinotecan. Interestingly, the FRF-BF (100 mg/kg,
      p.o) reduced the intestinal motility in mice and attenuated parameters linked to
      irinotecan-induced intestinal mucositis, including diarrhea, histological damage,
      depletion of duodenal GSH, amount of TNF-alpha, and MPO activity in the small
      intestine. Also, FRF-BF does not interfere in the antitumor activity of
      irinotecan and exerted antitumoral activity in murine melanoma. In conclusion,
      FRF-BF (100 mg/kg, p.o) presents promising pharmacological potential to prevent
      and attenuate the severity of intestinal mucositis during chemotherapy treatment,
      related to the presence of kaempferitrin.

PMID- 30281177
TI  - Effect of purslane on blood lipids and glucose: A systematic review and meta
      analysis of randomized controlled trials.
AB  - Despite a history of purslane usage as a herbal treatment for dyslipidemia and
      hyperglycemia management, existing evidence from clinical trials is
      controversial. The aim for the current study was to evaluate the efficacy of
      purslane supplementation on lipid parameters and glycemic status in adult
      populations. A systematic review was conducted in PubMed, Scopus, ISI Web of
      Science, and Google Scholar up to January 15, 2018, searching for randomized
      controlled trials that assessed the impact of purslane on fasting blood glucose
      (FBG), triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol
      (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Based on the detected
      heterogeneity between studies, a random- or fixed-effect model was applied in the
      meta-analysis. The findings from six randomized controlled trials, comprising 352
      participants, indicated that purslane can reduce FBG (-4.54 mg/dl, 95% CI [-7.54,
      -1.53]; I2  = 0.53%) and triglycerides (-19.16 mg/dl, 95% CI [-38.17, -0.15]; I2 
      = 0%) levels. Changes in TC, LDL-C, and HDL-C concentrations did not reach a
      statistically significant level. Subgroup analysis showed a favorable effects of
      purslane on FBG, triglycerides, TC, and LDL-C in a subset of studies in which
      purslane was administered >1.5 g/day. Categorization based on gender showed that
      purslane was more effective in improving FBG, TC and LDL-C in females compared
      with males. This systematic review and meta-analysis suggested that the purslane
      might be effective on the improvement of blood lipid and glucose levels. Further
      robust studies with sufficient durations and dosages of supplementation are
      needed to confirm these results.

PMID- 30281178
TI  - Factors associated with adherence to antimicrobial stewardship after-hours.
AB  - OBJECTIVES: Assess restricted antimicrobials acquired after standard working
      hours for adherence to antimicrobial stewardship (AMS) and identify factors
      associated with increased likelihood of adherence at the time of acquisition, and
      the next standard working day. METHODS: All documented antimicrobials acquired
      from a paediatric hospital after-hours drug room from 1 July 2014 to 30 June 2015
      were reconciled with records of AMS approval, and documented AMS review in the
      medical record. KEY FINDINGS: Of the 758 antimicrobial acquisitions from the
      after-hours drug room, 62.3% were restricted. Only 29% were AMS adherent at the
      time of acquisition, 15% took place despite documented request for approval by a
      pharmacist. Antimicrobials for respiratory patients (OR 3.10, 95% CI 1.68-5.5)
      and antifungals (2.48, 95% CI 1.43-4.30) were more likely to be AMS adherent.
      Half of the acquisitions that required review the next standard working day were
      adherent to AMS (51.8%, 129/249). Weekday acquisitions (2.10, 95% CI 1.20-3.69)
      and those for patients in paediatric intensive care (2.26, 95% CI 1.07-4.79) were
      associated with AMS adherence. Interactions with pharmacists prior to acquisition
      did not change the likelihood of AMS adherence the next standard working day.
      Access to restricted antimicrobial held as routine ward stock did not change the
      likelihood of AMS adherence at the time of acquisition, or the next standard
      working day. CONCLUSION: Restricted antimicrobials acquired after-hours are not
      routinely AMS adherent at the time of acquisition or the next standard working
      day, limiting opportunities for AMS involvement.

PMID- 30281179
TI  - Barriers to medication adherence in patients prescribed medicines for the
      prevention of cardiovascular disease: a conceptual framework.
AB  - OBJECTIVES: To identify barriers to medication adherence in patients prescribed
      medicines for the prevention of cardiovascular disease and map these to the
      Theoretical Domains Framework (TDF), to produce a conceptual framework for
      developing a questionnaire-based medication adherence tool. METHODS: A scoping
      review of barriers to medication adherence in long-term conditions was conducted
      to generate an initial pool of barriers. After preliminary mapping to the TDF,
      these barriers were presented to two focus groups of patients prescribed
      medicines for the prevention of cardiovascular disease (n = 14) to stimulate
      discussion. The group discussions enabled the patients' interpretations of the
      adherence barriers to be determined, provided validity from the patient
      perspective and identified additional barriers unrepresented in the scoping
      review. KEY FINDINGS: The preliminary pool of adherence barriers was identified
      from 47 studies across a range of long-term conditions. The majority of TDF
      domains were represented by these literature-identified barriers except
      'social/professional role and identity' and 'behavioural regulation'. Barrier
      mapping was largely endorsed by focus group participants, who also contributed
      additional barriers, including those relating to not having a 'system' in place
      for managing their medicines and the negative emotions evoked by medicine taking.
      CONCLUSION: The TDF enabled full exploration of adherence barriers including
      those relating to emotions which have received limited attention in the
      literature. This work has provided a conceptual framework for developing a
      questionnaire to identify an individual's adherence barriers which may then be
      coupled with appropriate behaviour change techniques to deliver a theory-based
      intervention tailored for individual need.

PMID- 30281180
TI  - A randomized controlled trial of oral chloral hydrate vs intranasal
      dexmedetomidine plus buccal midazolam for auditory brainstem response testing in
      children.
AB  - BACKGROUND: Moderate to deep sedation is required for an auditory brainstem
      response test when high-intensity stimulation is used. Chloral hydrate is the
      most commonly used sedative, whereas intranasal dexmedetomidine is increasingly
      used in pediatric non-painful procedural sedations. OBJECTIVE: The aim of this
      study was to compare the sedation success rate after oral chloral hydrate at 50
      mg kg-1 and intranasal dexmedetomidine at 3 MUg kg-1 plus buccal midazolam at 0.1
      mg kg-1 for an auditory brainstem response test. METHODS: Children who required
      an auditory brainstem response test were recruited and randomly assigned to
      receive oral chloral hydrate at 50 mg kg-1 and intranasal placebo, or intranasal
      dexmedetomidine at 3 MUg kg-1 with buccal midazolam 0.1 mg kg-1 . The primary
      outcome was the rate of successful sedation for auditory brainstem response
      tests. RESULTS: Fifty-seven out of 82 (69.5%) were successfully sedated after
      chloral hydrate, while 70 out of 78 (89.7%) children were successfully sedated
      with dexmedetomidine plus midazolam combination, with the odd ratio (95% CI) for
      successful sedation between dexmedetomidine plus midazolam combination and
      chloral hydrate estimated to be 3.84 (1.61-9.16), P = 0.002. Dexmedetomidine plus
      midazolam was associated with quicker onset with median onset time 15 (IQR 11.0
      19.8) for dexmedetomidine plus midazolam and 20 (IQR 15.0-27.0) for chloral
      hydrate respectively, with difference between median (95% CI) of 5 [3-8], P <
      0.0001). The behavior observed during drug administration of intranasal
      dexmedetomidine and buccal midazolam was better that of the children who had oral
      chloral hydrate. No children required oxygen therapy or medical intervention for
      hemodynamic disturbances in this study and the incidence of hypotension and
      bradycardia was similar. CONCLUSION: Intranasal dexmedetomidine plus buccal
      midazolam was associated with higher sedation success with deeper level of
      sedation, with similar discharge time and adverse event rate when compared to
      chloral hydrate.

PMID- 30281181
TI  - Anesthetic management of thoracoscopic resection of lung lesions in small
      children.
AB  - BACKGROUND: Video-assisted thoracoscopic surgery has dramatically increased over
      the last decade because of both medical and cosmetic benefits. Anesthesia for
      video-assisted thoracoscopic surgery in small children is more challenging
      compared to adults due to the considerable problems posed by small airway
      dimensions and ventilation. The optimal technique for one-lung ventilation has
      yet to be established and the use of remifentanil infusion in this setting is not
      well described. AIMS: This study investigated the use of extraluminal bronchial
      blocker placement for one-lung ventilation and the effect of infusion of
      remifentanil in infants and small children undergoing video-assisted
      thoracoscopic surgery. METHODS: We retrospectively reviewed the technique of one
      lung ventilation and the hemodynamic effects of remifentanil infusion in 31 small
      children during elective video-assisted thoracoscopic surgery for congenital lung
      lesions under anesthesia with sevoflurane or isoflurane, oxygen, and air.
      Patients' heart rate, blood pressure, and endtidal carbon dioxide at baseline
      (after induction of anesthesia), immediately after one-lung ventilation, during
      carbon dioxide insufflation, and at the end of one-lung ventilation were
      extracted from the database and analyzed. The use of vasopressors or
      dexmedetomidine was also recorded and analyzed. RESULTS: Extraluminal placement
      of a bronchial blocker alongside the tracheal tube was successfully performed in
      90.3% of cases (28 patients) without any serious complications or arterial oxygen
      desaturation. There was no significant rise in blood pressure or heart rate even
      with the rise of endtidal carbon dioxide concentration during video-assisted
      thoracoscopic surgery. In 58% of patients (18 patients), phenylephrine was
      administered to maintain the blood pressure within 20% of the baseline value.
      There was no significant change in the heart rate of all patients at each time
      point. CONCLUSION: One-lung ventilation with an extraluminal parallel blocker was
      used effectively in this series of young children undergoing thoracoscopic
      excision of congenital pulmonary lesions. Remifentanil infusion attenuated
      surgical stress effectively in infants and small children undergoing video
      assisted thoracoscopic surgery.

PMID- 30281182
TI  - Determination of the minimal alveolar concentration of sevoflurane associated
      with isoelectric electroencephalogram in children: A prospective, randomized,
      double-blind study.
AB  - OBJECTIVE: We investigated the minimal alveolar concentration (MAC) of
      sevoflurane associated with the occurrence of isoelectric electroencephalogram in
      50% of children under steady-state conditions (MAC IE). The MAC IE was determined
      in 100% oxygen and with the addition of 50% nitrous oxide or after the injection
      of fentanyl. METHODS: Seventy-two children (ASA I or II, age 3-8 years)
      undergoing elective surgery were allocated to one of three groups: in 100% oxygen
      (group O2 ), in 50% oxygen and 50% nitrous oxide (group N2 O), or in 100% oxygen
      with a bolus of 3 MUg/kg fentanyl (group FENTANYL). The state of isoelectric EEG
      was considered as significant when a burst suppression ratio of 100% lasted for
      >1 minute. The MAC IE was determined by the Dixon's up-and-down method after a 15
      minute period with a stable endtidal concentration of sevoflurane. The
      concentration of sevoflurane was determined by the electroencephalogram of the
      previous patient: increase of 0.2% if isoelectric EEG were absent or decrease of
      0.2% if isoelectric EEG were present. RESULTS: The MAC IE in group O2 (MAC IEO 2
      ) was 5.30 (5.12-5.48)% (median [95% CI]). The MAC IE in group N2 O (MAC IEN 2O )
      was 5.83 (5.67-5.99)%. The MAC IE in group FENTANYL (MAC IEFENTANYL ) was 5.37
      (5.21-5.53)%, which was close to MAC IEO 2 . CONCLUSION: The MAC IE of
      sevoflurane calculated in 100% O2 was 5.30% in children. Addition of 50% N2 O
      modestly increased MAC IE of sevoflurane, while 3 MUg/kg fentanyl had no effect
      on MAC IE of sevoflurane.

PMID- 30281183
TI  - Clinical Comparative Evaluation of Nd:YAG Laser and a New Varnish Containing
      Casein Phosphopeptides-Amorphous Calcium Phosphate for the Treatment of Dentin
      Hypersensitivity: A Prospective Study.
AB  - PURPOSE: The aim of this study was to compare the effect of Nd:YAG laser to that
      of a new varnish: MI Varnish with RECALDENT (GC), for the treatment of dentin
      hypersensitivity, with a follow-up of 6 months. Dentinal hypersensitivity was
      evaluated using a new thermal test never before used on dental tissue. MATERIALS
      AND METHODS: A split-mouth design was used where teeth on one side received the
      same type of treatment. Twelve patients suffering from dentin hypersensitivity
      were chosen. Fifty-four teeth were divided into 27 pairs. Twenty-seven teeth
      received the Nd:YAG laser treatment, and the 27 contralateral teeth received MI
      Varnish application. Five parameters were measured, and the measurements were
      taken before treatment at baseline (T0), after 1 week (T1), 1 month (T2), 3
      months (T3), and 6 months (T4) of the application. Air stimulation to obtain the
      Schiff air score, the score of discomfort according to the visual analog scale
      (VAS), the tactile score, and the thermal test that determines the minimum cold
      stimulating temperature and the maximum heat-stimulating temperature were all
      used to assess sensitivity. Statistical analyses of the data were performed, and
      the significance level was set at p <= 0.05. Exact Fisher tests and Chi-Square
      tests were conducted to compare percentages. RESULTS: There was a clear decrease
      in dentin hypersensitivity for both treatments (Nd:YAG laser and MI Varnish)
      especially between baseline and 1 week, with maintenance of this state through
      the 6-month follow-up period. The difference between the two treatments was not
      significant, comparing, over time, the Schiff air score, the thermal test, and
      the VAS; however, the tactile score was significantly improved 6 months after the
      application of MI Varnish compared to the laser (p = 0.05). CONCLUSION: There was
      no significant difference between the two treatments, Nd:YAG laser and MI
      Varnish. Both treatments were effective and reduced dentin hypersensitivity
      immediately after treatment up to 6 months.

PMID- 30281184
TI  - Physical activity and sedentary behaviour in a residential aged care facility.
AB  - OBJECTIVE: To evaluate sedentary behaviour and physical activity levels in
      independently mobile older adults with and without dementia living in residential
      aged care. METHODS: Sedentary behaviour and physical activity were measured in 37
      residents of an aged care facility using an accelerometer worn during waking
      hours for five days. RESULTS: Participants with valid accelerometer data (n = 28)
      spent 85% of the time sedentary, and 12% in low-intensity, 2% in light-intensity
      and 1% in moderate-to-vigorous-intensity physical activity. Over half of
      sedentary time was accumulated in bouts of greater than 30 minutes. Physical
      activity at any level of intensity was performed in bouts of less than 10
      minutes. CONCLUSION: Residents were highly sedentary and inactive. In particular,
      the short duration of each bout of activity amongst lengthy periods of sedentary
      behaviour was a substantial finding. The study suggests the need to develop
      innovative ways of breaking up sedentary behaviour in residential aged care.

PMID- 30281185
TI  - Diagnosis and perioperative management in pediatric sleep-disordered breathing.
AB  - Sleep-disordered breathing has a prevalence of 12% in the pediatric population.
      It represents a spectrum of disorders encompassing abnormalities of the upper
      airway that lead to sleep disruption, including primary snoring, obstructive
      sleep apnea, central sleep apnea, and sleep-related hypoventilation. Sleep
      disordered breathing is the most common indication for adenotonsillectomy, one of
      the most common procedures performed in children. In recent years, the American
      Academy of Otolaryngology-Head and Neck Surgery, American Academy of Pediatrics,
      and the American Society of Anesthesiologists have crafted guidelines to help
      safely manage children with sleep-disordered breathing. Each organization
      recommends in-laboratory polysomnography for definitive diagnosis of obstructive
      sleep apnea in certain cases. However, because this test is both costly and
      inconvenient, there has been significant interest in alternative methods for
      diagnosing clinically significant sleep-disordered breathing. Accurate diagnosis
      is critical because sleep-disordered breathing confers certain perioperative
      risks and increased mortality in some instances. Recent studies have elucidated
      the danger of anesthesia and opioids in worsening obstructive sleep apnea, and
      recommendations for alternative analgesia are being created. In addition,
      determining the most appropriate level and duration of monitoring in the
      postoperative period is actively being evaluated. This article presents an
      overview of the recent literature on the perioperative care of pediatric patients
      with sleep-disordered breathing. It highlights innovative modalities and
      limitations in diagnosing obstructive sleep apnea, the importance of a tailored
      anesthetic/analgesic approach to children with obstructive sleep apnea, and the
      need for postoperative monitoring. It also brings to focus that further studies
      on the perioperative care of these children are necessary.

PMID- 30281186
TI  - Trends in adverse drug reactions related hospitalisations over 13 years in New
      South Wales, Australia.
AB  - AIMS: To examine trends in adverse drug reactions (ADR)-related hospitalisations
      in New South Wales (NSW). METHODS: Data were extracted from the Admitted Patient
      Data Collection (APDC), a census of hospital separations in NSW. We estimated age
      adjusted rates of ADE-related hospitalisation between 1st July 2001 and 30th June
      2014, and rates by patient characteristics, main therapeutic medication groups,
      and clinical condition groups that warranted the hospitalisation. We used the
      percent change annualised estimator to evaluate rates over time. RESULTS: A total
      of 315,274 NSW residents admitted for urgent care of ADRs were identified. The
      age-adjusted rates of ADR-related hospitalisations nearly doubled and increased
      by 5.8% (95%CI: 5.0-6.6%) per annum, with in-hospital death rate increase of 2.4%
      (1.6-3.3%). Agranulocytosis (2.7%), nausea and vomiting (2.4%), and heart failure
      (2.4%) were the most common conditions that lead to ADR-related hospitalisations
      over 13 years, with acute renal failure (1.4%) recently emerging as the leading
      adverse condition. Participants aged between 65 and 84 years accounted for nearly
      half of ADR-hospitalisations (45.6%), with age-adjusted rate increasing from
      103.9 in 2001-02 to 189.0 per 100,000 NSW residents in 2013-14. Anticoagulants
      (13.5%) were the most common medications contributing to ADR-related
      hospitalisation, followed by opioid analgesics (9.6%). CONCLUSIONS: ADR-related
      hospitalisation remains a population health burden with significant increase over
      time. The findings call for continuing efforts to prevent ADRs, especially among
      high risk populations such as older people. This article is protected by
      copyright. All rights reserved.

PMID- 30281187
TI  - Expectations of care within marriage for older couples.
AB  - OBJECTIVES: This study explores the intersection of marriage and caregiving
      amongst older spousal caregivers in regional Australia. Specifically, we address
      the research question: 'How do expectations of informal care impact spousal
      caregivers in later life?' METHODS: These comprise interpretive qualitative in
      depth interviews in order to understand the lived experience of caregiving within
      the context of long-term marriage. RESULTS: Findings highlight the complexity and
      diversity of marital relationships as the context of informal care. Individual
      and social obligations were evident in key themes, demonstrating how spouses
      automatically assume and continue in caregiver roles in later life. CONCLUSION:
      Caregiving is an expectation of couples in long-term marriages, regardless of the
      relationship quality and willingness to care. Normative expectations also impact
      decision-making around future care planning and transitions away from home-based
      care. These are important considerations for both policy and practice with older
      adults and their caregivers.

PMID- 30281188
TI  - Newly proposed electrocardiographic criteria for the diagnosis of left
      ventricular hypertrophy in a Chinese population.
AB  - BACKGROUND: The electrocardiographic criteria currently available for the
      diagnosis of left ventricular hypertrophy (LVH) are low in sensitivity. Thus, we
      compared the diagnostic performance of newly proposed electrocardiographic
      criteria to the existing criteria in a Chinese population. METHODS: A total of
      235 consecutive hypertensive patients, hospitalized in our department between May
      2017 and April 2018, were included. They were divided into two groups based on
      the gold standard echocardiogram: those with (n = 116) and without LVH (n = 119).
      The newly proposed ECG criteria were calculated by summating the amplitude of the
      deepest S wave (SD ) in any single lead and the S-wave amplitude of lead V4 (SV4
      ). The area under the curve was calculated and compared against the sex-specific
      Cornell limb lead and Sokolow-Lyon criteria. RESULTS: ECG analysis of the cohort
      showed that the newly proposed criteria had the highest sensitivity in diagnosing
      LVH (male: 65.5%; female: 81%), followed by the Cornell limb lead criteria (male:
      55.2%; female: 56.9%). The specificities of both sets of criteria were higher
      than 70%, with no significant differences between them. Receiver operator curve
      analysis showed an optimal cutoff of >=2.1 mV for females (AUC: 0.832; 95% CI:
      0.757-0.906) and >=2.6 mV for males (AUC: 0.772; 95% CI: 0.687-0.856).
      CONCLUSION: The newly proposed SD  + SV4 criteria provide an improved sensitivity
      for the ECG diagnosis of LVH compared to existing criteria, but its routine use
      will require further validation in larger populations.

PMID- 30281189
TI  - Predicting tubal factor infertility by using markers of humoral and cell-mediated
      immune response against Chlamydia trachomatis.
AB  - PROBLEM: The accuracy of Chlamydia trachomatis antibody test in predicting tubal
      factor infertility (TFI) is limited, and more accurate methods are needed. Cell
      mediated immune response (CMI) is crucial in the resolution of pathogen, but it
      may play an important role in the pathogenesis of C trachomatis-associated tubal
      damage. We studied whether combining the markers of C trachomatis-induced CMI to
      humoral immune response improves the accuracy of serology in TFI prediction.
      METHOD OF STUDY: Our prospective study consists of 258 subfertile women, of whom
      22 (8.5%) had TFI. Women with other causes for subfertility served as a reference
      group. Serum C trachomatis major outer membrane protein (MOMP) and chlamydial
      heat-shock protein 60 (cHSP60) IgG antibodies were measured by ELISA. CMI was
      studied by lymphocyte proliferation assay in vitro. RESULTS: Serological markers
      were more prevalent in women with TFI than in other subfertile women (40.9% vs
      12.3% for MOMP IgG and 27.3% vs 10.2% for cHSP60 IgG). The best test combination
      for TFI was C. trachomatis MOMP and cHSP60 antibody with an accuracy of 90.3%,
      sensitivity of 22.7% and specificity of 96.6%. Positive post-test probability of
      this combination was 54.2%, and negative post-test probability was 12.4%. Adding
      of the markers of CMI did not significantly improve the accuracy of serology in
      TFI prediction. CONCLUSION: The accuracy of TFI prediction increases when the
      combination of C trachomatis MOMP and cHSP60 antibody tests is used. C
      trachomatis-induced CMI was common in our study population, but the markers of
      CMI did not predict TFI.

PMID- 30281191
TI  - Shark Fin Titanium Hollow Bulb Obturator: A Treatment Concept.
AB  - Restoring esthetics and function for patients with maxillectomy defects presents
      a complex challenge for the clinician. Obturator prostheses are subject to
      rotational forces during function, allowing movement into the defect. Gaining
      prosthesis support from endosseous implants can limit the amount of rotation.
      Xerostomia and impaired tissue healing caused by radiation therapy further
      complicates the treatment for such patients. Several resilient and rigid
      obturator design concepts are available for restoration of such defects. This
      clinical report describes a design concept used to treat a patient with a
      maxillectomy defect caused by tumor resection secondary to a squamous cell
      carcinoma.

PMID- 30281192
TI  - The use of chromium (III) complexes to enhance peptide protonation by
      electrospray ionization mass spectrometry.
AB  - The addition of trivalent chromium, Cr (III), reagents to peptide solutions can
      increase the intensity of doubly protonated peptides, [M + 2H]2+ , through
      electrospray ionization (ESI). Three model heptapeptides were studied: neutral
      (AAAAAAA), acidic (AAEEEAA), and basic (AAAKAAA). The neutral and acidic peptides
      form almost no 2+ ions in the absence of Cr (III). Twenty Cr (III) complexes were
      used as potential enhanced protonation reagents, including eleven complexes with
      non-labile ligands and nine with labile ligands. The complexes that provide the
      most abundant [M + 2H]2+ , the greatest [M + 2H]2+ to [M + H]+ ratio, and the
      cleanest mass spectra are [Cr(H2 O)6 ](NO3 )3 .3H2 O and [Cr (THF)3 ]Cl3 . Anions
      in Cr (III) reagents can also affect the intensity of [M + 2H]2+ and the [M +
      2H]2+ to [M + H]+ ratio through cation-anion interactions. The influence of
      anions on the extent of peptide protonation follows the trend ClO4 - ? SO4 2- ?
      Br- ? Cl- ? F- ~ NO3 - . Solvent effects and complexes with varying number of
      water ligands were investigated to study the importance of water in enhanced
      protonation. Aqueous solvent systems and Cr (III) complexes that have at least
      one bound water ligand in solution must be used for successful increase in the
      intensity of [M + 2H]2+ , which indicates that water is involved in the mechanism
      of Cr (III)-induced enhanced protonation. The ESI source design is also important
      because no enhanced protonation was observed using a Z-spray source. The current
      results suggest that this Cr (III)-induced effect occurs during the ESI
      desolvation process.

PMID- 30281193
TI  - Successful use of "Choice Architecture" and "Nudge Theory" in a quality
      improvement initiative of analgesia administration after Caesarean section.
AB  - BACKGROUND: Regular, routine, multimodal analgesia provides better pain relief
      following Caesarean section than reliance on "as required" opiate dosing. This
      quality improvement report describes the effective use of an education programme
      coupled with a highlighted, preprinted medication chart, employing "Nudge Theory"
      principles to achieve significant improvements in the administration of analgesic
      medications to patients after Caesarean section operations. PROBLEM: An acute
      pain service audit identified a serious deficiency with delivery of regular
      postoperative analgesic medications to patients following Caesarean section
      operations. METHODS: An audit of pain medication delivery to patients following
      Caesarean section demonstrated that postoperative analgesia was not being
      administered in line with local prescribing guidelines. Two interventions were
      planned: Education sessions for anaesthetic recovery and ward staff. Introduction
      of a new preprinted and highlighted medication chart. A postintervention audit
      was then conducted. RESULTS: There were statistically significant improvements in
      all medications administered to patients following the two interventions. For
      analgesic medications, the rate of administration of drugs in compliance with
      guidelines rose from 39.6% to 89.9% (P < 0.001 using 2-sample z test). Each
      subgroup of medications also showed statistically significant improvements in
      administration compliance. CONCLUSION: A combined approach, including application
      of "Nudge Theory" to the administration of analgesic medication after Caesarean
      section, considerably improved delivery of medications prescribed for
      postoperative analgesia.

PMID- 30281194
TI  - A Janus Nickel Cobalt Phosphide Catalyst for High-Efficiency Neutral-pH Water
      Splitting.
AB  - Transition-metal phosphides have stimulated great interest as catalysts to drive
      the hydrogen evolution reaction (HER), but their use as bifunctional catalytic
      electrodes that enable efficient neutral-pH water splitting has rarely been
      achieved. Herein, we report the synthesis of ternary Ni0.1 Co0.9 P porous
      nanosheets onto conductive carbon fiber paper that can efficiently and robustly
      catalyze both the HER and water oxidation in 1 m phosphate buffer (PBS; pH 7)
      electrolyte under ambient conditions. A water electrolysis cell comprising the
      Ni0.1 Co0.9 P electrodes demonstrates remarkable activity and stability for the
      electrochemical splitting of neutral-pH water. We attribute this performance to
      the new ternary Ni0.1 Co0.9 P structure with porous surfaces and favorable
      electronic states resulting from the synergistic interplay between nickel and
      cobalt. Ternary metal phosphides hold promise as efficient and low-cost catalysts
      for neutral-pH water splitting devices.

PMID- 30281195
TI  - Perioperative respiratory adverse event risk assessment in children with upper
      respiratory tract infection: Validation of the COLDS score.
AB  - BACKGROUND: The decision to proceed with anesthesia and surgery has been
      controversial in pediatric patients with an upper respiratory tract infection.
      The COLDS score was proposed by Lee and August as a potential risk stratification
      scheme, but no validation has been performed on this scale. AIMS: The aim of this
      study was to evaluate the utility of the COLDS score in predicting perioperative
      respiratory adverse events and optimize its predictive ability. METHODS: COLDS
      scores, incidence of perioperative respiratory adverse events, surgical procedure
      type, and age were prospectively collected for 536 patients who met inclusion
      criteria. Area under the receiver operating characteristic curves was computed
      for total COLDS score and individual COLDS score categories. Multivariable
      regression was used create an optimized score. To quantify the decrease in risk
      associated with case cancelation due to illness, the other risk factors in COLDS
      were assessed separately from upper respiratory infection status and a risk model
      was created. RESULTS: The area under the receiver operating characteristic curve
      for the total COLDS score was 0.69, suggesting that the COLDS score has a
      moderate predictive ability for perioperative respiratory adverse events. When
      split into individual component scores, the area under the receiver operating
      characteristic curve ranged from 0.55 to 0.63. We also found that the area under
      the receiver operating characteristic curve for the scoring system was higher in
      younger children than for children aged 4-6 (area under receiver operating
      characteristic curve of 0.70-0.71 vs 0.66). The area under the receiver operating
      characteristic curve for the optimized scoring system was 0.71. CONCLUSION: The
      COLDS score has the potential to be a valuable risk assessment tool for
      prediction of perioperative respiratory adverse events and appears to have a
      better predictive value in certain subpopulations.

PMID- 30281196
TI  - A sluggish mid-Proterozoic biosphere and its effect on Earth's redox balance.
AB  - The possibility of low but nontrivial atmospheric oxygen (O2 ) levels during the
      mid-Proterozoic (between 1.8 and 0.8 billion years ago, Ga) has important
      ramifications for understanding Earth's O2 cycle, the evolution of complex life
      and evolving climate stability. However, the regulatory mechanisms and redox
      fluxes required to stabilize these O2 levels in the face of continued biological
      oxygen production remain uncertain. Here, we develop a biogeochemical model of
      the C-N-P-O2 -S cycles and use it to constrain global redox balance in the mid
      Proterozoic ocean-atmosphere system. By employing a Monte Carlo approach bounded
      by observations from the geologic record, we infer that the rate of net
      biospheric O2 production was 3.5-1.1+1.4 Tmol year-1 (1sigma), or ~25% of today's
      value, owing largely to phosphorus scarcity in the ocean interior. Pyrite burial
      in marine sediments would have represented a comparable or more significant O2
      source than organic carbon burial, implying a potentially important role for
      Earth's sulphur cycle in balancing the oxygen cycle and regulating atmospheric O2
      levels. Our statistical approach provides a uniquely comprehensive view of Earth
      system biogeochemistry and global O2 cycling during mid-Proterozoic time and
      implicates severe P biolimitation as the backdrop for Precambrian geochemical and
      biological evolution.

PMID- 30281197
TI  - Fear of Childbirth, Postpartum Depression, and Birth-Related Variables as
      Predictors of Posttraumatic Stress Disorder After Childbirth.
AB  - BACKGROUND: Childbirth may be a significant cause of postpartum posttraumatic
      stress disorder (PTSD) in women. AIMS: The objective of this study is to examine
      the effect of fear of childbirth, postpartum depression, and certain birth
      related variables on postpartum PTSD. METHODS: This study is a cross-sectional
      study. The study was carried out in a maternity hospital nonstress unit between
      December 1, 2015, and February 29, 2016. Three hundred and one pregnant women who
      met the criteria for inclusion in the study made up the research sample. RESULTS:
      Fear of childbirth and postpartum depression significantly and positively
      predicted the level of posttraumatic stress after childbirth (beta = 0.17, p <
      .01; beta = 0.68, p < .001). Fear of childbirth explains 3% of the total variance
      in posttraumatic stress (R2  = .03, adjusted R2  = .02, F = 7.141, p < .01),
      while postpartum depression explains 47% of it (R2  = .47, adjusted R2  = .46, F
      = 196.35, p < .001). Satisfaction with the attitudes of the medical staff during
      childbirth, defining the childbirth experience, and the state of experiencing
      postpartum problems by the mother are significant predictors of postpartum
      posttraumatic stress (beta = -0.21, p < .01; beta = -0.14, p < .05; beta = 0.17,
      p < .01). When these three variables are addressed together, they explain 14% of
      the total variance (R2  = .14, adjusted R2  = .13, F = 9.33, p < .001). LINKING
      EVIDENCE TO ACTION: Postpartum PTSD is a situation that must be carefully
      emphasized in terms of maternal, baby, and family health. For this reason, it is
      necessary to evaluate postpartum PTSD more quickly and objectively, and
      healthcare providers have major duties in this respect.

PMID- 30281199
TI  - Supplements.

PMID- 30281198
TI  - A hybrid planning strategy for stereotactic body radiation therapy of early stage
      non-small-cell lung cancer.
AB  - Currently dynamic conformal arcs (DCA) and volumetric modulated arc therapy
      (VMAT) are two popular planning techniques to treat lung stereotactic body
      radiation therapy (SBRT) patients. Of the two, DCA has advantages in terms of
      multi-leaf collimator (MLC) motion, positioning error, and delivery efficiency.
      However, VMAT is often the choice when critical organ sparing becomes important.
      We developed a hybrid strategy to incorporate DCA component into VMAT planning,
      results were compared with DCA and VMAT plans. Four planning techniques were
      retrospectively simulated for 10 lung SBRT patients: DCA, Hybrid-DCA (2/3 of the
      doses from DCA beams), Hybrid-VMAT (2/3 of the doses from VMAT beams) and VMAT.
      Plan complexity was accessed by modulation complexity score (MCS). Conformity
      index (CI) for the planning target volume (PTV), V20 and V5 for the lung, V30 for
      the chestwall, and maximum dose to all other critical organs were calculated.
      Plans were compared with regard to these metrics and measured agreement between
      the planned and delivered doses. DCA technique did not result in acceptable plan
      quality due to target location for five patients. Hybrid-DCA produced one
      unacceptable plan, and Hybrid-VMAT and VMAT produced no unacceptable plans. The
      CI improved with increasing VMAT usage, as did the dose sparing to critical
      structures. Compared to the VMAT technique, a total MU reduction of 14%, 25% and
      37% were found for Hybrid-VMAT, Hybrid-DCA and DCA techniques for 54 Gy patient
      group, and 9%, 23% and 34% for 50 Gy patient group, suggesting improvement in
      delivery efficiency with increasing DCA usage. No significant variations of plan
      complexity were observed between Hybrid-DCA and Hybrid-VMAT (P = 0.46 from Mann
      Whitney U-test), but significant differences were found among DCA, Hybrid and
      VMAT (P < 0.05). Better agreements between the planned and delivered doses were
      found with more DCA contributions. By adding DCA components to VMAT planning,
      hybrid technique offers comparable dosimetry to full VMAT, while increasing
      delivery efficiency and minimizing MLC complexity.

PMID- 30281200
TI  - Ethnic disparities in relationships of obesity indices with telomere length in
      Asians with type 2 diabetes.
AB  - BACKGROUND: Obesity and shorter telomeres increase the risk for diabetes
      complications and mortality. However, the relationship between obesity and
      telomere length in diverse Asian populations with type 2 diabetes (T2D) is not
      well understood. This study examined the association of baseline and changes in
      obesity indices with telomere length in multiethnic Asian populations with T2D.
      METHODS: Leukocyte telomere length (LTL) was measured by quantitative polymerase
      chain reaction in the SMART2D cohort (n = 1431 at baseline, n = 1039 after 3.2
      years median follow-up). Associations between obesity indices and LTL were
      assessed by linear regression. RESULTS: Compared with Chinese, LTL was longer in
      Malays (P < 0.0001) and similar in Indians. Cross-sectionally, body mass index
      (BMI)-adjusted (residual) visceral fat area (VFA; beta = -0.004, P = 0.006), and
      waist-to-hip ratio (beta = -1.95, P = 0.030) were significantly associated with
      LTL in Chinese but not in Malays and Indians. Changes in BMI (r = -0.080; P =
      0.053) and VFA (r = -0.126; P = 0.002) were inversely correlated with changes in
      LTL only in Chinese. Furthermore, in Chinese, 1-SD incremental changes in BMI
      (beta = -0.070; P = 0.040) and VFA (beta = -0.088, P = 0.028) were significantly
      associated with larger telomere attrition, independent of age, sex, diabetes
      condition, baseline LTL, obesity, and inflammation markers. CONCLUSIONS: Three
      year changes in BMI and VFA were associated with telomere dynamics in Chinese but
      not in Malays and Indians with T2D. Reducing obesity may reduce the risk of
      diabetes complications associated with shorter LTL in the Chinese population.

PMID- 30281201
TI  - Global Profiling of PknG Interactions Using a Human Proteome Microarray Reveals
      Novel Connections with CypA.
AB  - Mycobacterium tuberculosis (Mtb) serine/threonine kinase PknG plays an important
      role in the Mtb-host interaction by facilitating the survival of Mtb in
      macrophages. However, the human proteins with which the PknG interacts, and the
      underlying molecular mechanisms are still largely unknown. In this study, a
      HuProt array is been applied to globally identify the host proteins to which PknG
      binds. In this way, 125 interactors are discovered, including a cyclophilin
      protein, CypA. This interaction between PknG and CypA is validated both in vitro
      and in vivo, and functional studies show that PknG significantly reduces the
      protein levels of CypA through phosphorylation, which consequently inhibit the
      inflammatory response through downregulation of NF-kappaB and ERK1/2 pathways.
      Phenotypically, overexpression of PknG reduces cytokine levels and promotes the
      survival of Mycobacterium smegmatis (Msm) in macrophages. Overall, it is expected
      that the PknG interactors identified in this study will serve as a useful
      resource for further systematic studies of the roles that PknG plays in the Mtb
      host interactions.

PMID- 30281202
TI  - Rheumatic syndromes associated with immune-checkpoint inhibitors: a single-center
      cohort of 61 patients.
AB  - OBJECTIVES: To describe the prevalence, clinical presentation, and management of
      rheumatic immune-related adverse effects (Rh-irAEs) from immune checkpoint
      inhibitor therapy. METHODS: From a database of all patients who received any
      immune-checkpoint inhibitor at the Mayo Clinic Rochester, Minnesota campus
      between January 1st, 2011 and March 1st, 2018, we retrospectively identified
      those with Rh-irAEs using diagnostic codes, search terms, and manual chart
      review. RESULTS: Of the 1,293 patients who received any checkpoint inhibitor, 43
      were clinically diagnosed with Rh-irAEs. Eighteen patients with Rh-irAEs who
      received ICI therapy elsewhere were also analyzed. Clinical syndromes included
      inflammatory arthritis (IA) (n=34, prevalence 2%), myopathy (n=10), and other
      rheumatic syndromes (n=17). IA was most commonly polyarticular and 26 patients
      (76%) required glucocorticoids. Mean treatment duration was 18 weeks (SD 18
      weeks). Five patients (15%) also received disease-modifying drugs and 3 patients
      (9%) required discontinuation of ICI therapy. Myopathy was treated with
      glucocorticoids in all cases for a mean duration of 15 weeks (SD 17 weeks) and
      lead to two deaths and permanent ICI discontinuation in 9 patients (90%). Other
      syndromes included connective tissue diseases, vasculitis, PMR-like syndrome, and
      flared pre-existing rheumatic disease. Most (71%) were treated with
      immunosuppression with 12% requiring ICI discontinuation. CONCLUSION: This study
      represents the largest cohort of Rh-irAEs to date. Most patients received long
      courses of immune suppression, though only a minority required ICI
      discontinuation. This article is protected by copyright. All rights reserved.

PMID- 30281204
TI  - Dr David Pothier 1973-2018: Associate Editor; Correspondence, Letters.

PMID- 30281203
TI  - Monoacylglycerol and diacylglycerol production by hydrolysis of refined vegetable
      oil by-products using an immobilized lipase from Serratia sp. W3.
AB  - Unlike the synthetic surfactants, mono- and diacylglycerols have the advantage to
      be biodegradable and non-toxic. In the present work, the hydrolysis of lipid
      fraction by-products of refined vegetable oils was performed by Serratia sp. W3
      lipase immobilized on CaCO3 by combined adsorption and precipitation. This
      support was selected out of four carriers as it exhibited the finest activity
      support (950 U/g) and the most satisfactory behavior at use. The immobilized
      preparation with CaCO3 was stable and active in the whole range of pH (4 to 9)
      and temperature (37 to 55 degrees C), yielding a 75% degree of hydrolysis at
      optimal environmental conditions of pH 8.5 and temperature 55 degrees C. Thin
      layer chromatography, gas chromatography, and liquid chromatography methods were
      evaluated to determine the analytical characterization of hydrolysis products.
      For monoacylglycerols and diacylglycerol fractions identified in the samples, a
      novel approach by liquid chromatography method was employed, through a homemade
      linear retention index database and a dedicated software. The adopted approach
      allowed the use of basic instrumentation set-ups, without the need of
      sophisticated detectors, such as mass spectrometers. Thus, it could be an
      effective alternative to produce emulsifiers from cheap vegetable oils.

PMID- 30281205
TI  - Altered Cervical Spinal Cord Resting State Activity in Fibromyalgia.
AB  - OBJECTIVE: Altered afferent input and central neural modulation are thought to
      contribute to fibromyalgia symptoms, and these processes converge within the
      spinal cord. We hypothesized that, using resting state functional magnetic
      resonance imaging (rs-fMRI) of the cervical spinal cord, we would observe altered
      frequency dependent activity in fibromyalgia. METHODS: Cervical spinal cord rs
      fMRI was performed in fibromyalgia patients and healthy controls. We analyzed a
      measure of low frequency oscillatory power, the amplitude of low frequency
      fluctuations (ALFF), for frequencies 0.01 - 0.198 Hz and frequency sub-bands, to
      determine regional and frequency-specific alterations in fibromyalgia. Functional
      connectivity and graph metrics were also analyzed. RESULTS: As compared to
      controls, greater ventral and lesser dorsal Mean ALFF of the cervical spinal cord
      was observed in fibromyalgia (p < 0.05, uncorrected) for frequencies 0.01 - 0.198
      Hz and all sub-bands. Additionally, lesser Mean ALFF within the right dorsal
      quadrant (p < 0.05, corrected) for frequencies 0.01 - 0.198 Hz and sub-band
      frequencies 0.073 - 0.198 Hz was observed in fibromyalgia. Regional Mean ALFF was
      not correlated with pain, however, regional lesser Mean ALFF was correlated with
      fatigue in patients (r = 0.763, p = 0.001). Functional connectivity and graph
      metrics were similar between groups. CONCLUSION: Our results indicate unbalanced
      activity between the ventral and dorsal cervical spinal cord in fibromyalgia.
      Increased ventral neural processes and decreased dorsal neural processes may
      reflect the presence of central sensitization and contribute to fatigue and other
      bodily symptoms in fibromyalgia. This article is protected by copyright. All
      rights reserved.

PMID- 30281206
TI  - Do Consumers Think Front-of-Package "High in" Warnings are Harsh or Reduce their
      Control? A Test of Food Industry Concerns.
AB  - OBJECTIVE: This study aimed to test the industry claim that "high in" front-of
      package (FOP) labeling systems are perceived as harsh and reduce consumers'
      control over food choices. METHODS: Respondents aged 16 to 32 years completed a
      between-group experimental task in an online survey (n = 1,000). Participants
      viewed a beverage with one of four FOP labels (text-only, octagon, triangle, or
      health star rating) and rated the label on its "harshness" and whether it made
      them feel more or less "in control" of their healthy eating decisions. RESULTS:
      Across all label conditions, at least 88% of respondents indicated the symbols
      were "about right" or "not harsh enough." At least 93% felt the symbols made them
      feel "more in control" or "neither less nor more in control." Participants
      viewing the health star rating were more likely to rate the symbol as "not harsh
      enough" and less likely to state that the symbol made them feel "more in
      control." CONCLUSIONS: There was no evidence to support industry claims that
      consumers perceive "high in" FOP symbols as harsh or as restricting their
      control. Indeed, most participants reported that the symbols were about the right
      harshness, and that they increased their control, including "stop sign" FOP
      symbols similar to those implemented in Chile.

PMID- 30281207
TI  - Characteristics of Usual Physical Therapy Post-Total Knee Replacement and their
      Associations with Functional Outcomes.
AB  - OBJECTIVE: Although total knee replacement surgery (TKR) is highly prevalent and
      generally successful, functional outcomes post-TKR vary widely. Most patients
      receive some physical therapy (PT) following TKR, but PT practice is variable and
      associations between specific content and dosage of PT interventions and
      functional outcomes are unknown. Research has identified exercise interventions
      associated with better outcomes but studies have not assessed whether such
      evidence has been translated into clinical practice. We characterized the
      content, dosage and progression of usual post-acute PT services following TKR,
      and examined associations of specific details of post-acute PT with patients' 6
      month functional outcomes. METHODS: Post-acute PT data were collected from
      patients undergoing primary unilateral TKR and participating in a clinical trial
      of a phone-based coaching intervention. PT records from the terminal episode of
      care were reviewed and utilization and exercise content data were extracted.
      Descriptive statistics and linear regression models characterized PT treatment
      factors and identified associations with 6-month outcomes. RESULTS: We analyzed
      112 records from 30 PT sites. Content and dosage of specific exercises and
      incidence of progression varied widely. Open chain exercises were utilized more
      frequently than closed chain (median and interquartile range (21(4,49) vs
      13(4,28.5)). Median (interquartile range) occurrence of progression of closed and
      open chain exercise was 0 (0,2) and 1 (0,3) respectively. Shorter timed stair
      climb was associated with greater total number of PT interventions and use and
      progression of closed chain exercises. DISCUSSION: Data suggest that evidence
      based interventions are under-utilized and dosage may be insufficient to obtain
      optimal outcomes. This article is protected by copyright. All rights reserved.

PMID- 30281209
TI  - A Novel Strategy to Investigate Tissue-Secreted Tumor Microenvironmental Proteins
      in Serum toward Development of Breast Cancer Early Diagnosis Biomarker Signature.
AB  - PURPOSE: The study aims to discover and identify early grade diagnosis markers in
      tumor microenvironment and investigates their expression in serum. EXPERIMENTAL
      DESIGN: 2D fluorescence difference gel electrophoresis (2D-DIGE), a gel-based
      proteomics platform is used for tissue profiling and identifies deregulated
      proteins by matrix-assisted laser desorption/ionization-time-of-flight mass
      spectrometry. Western blot validation for statistically significant six different
      proteins is performed in an independent cohort of participant serum. RESULTS:
      Total 67 nonredundant tissue proteins are identified out of 230 protein spots
      obtained through Marker selection tool of EDA. GELS, DAPLE, IQCC, CATD, A1AT, and
      HS90B are selected for validation and found to be upregulated in early grade
      serum samples. Pathway analysis performed through PANTHER and DAVID indicates
      that apoptosis, CCKR, EGF, FAS, FGF, Wnt, p13 kinase, and p53 signaling pathways
      are expressed specifically during or early onset of grade I cancer lesions.
      CONCLUSIONS AND CLINICAL RELEVANCE: GELS, DAPLE, HS90B, A1AT, IQCC, and CATD may
      be promising potential serum biomarker signature for diagnosis of early grade
      breast cancer. This panel also contributes to better understanding of molecular
      mechanisms involved in inceptive stage of breast cancer.

PMID- 30281208
TI  - Mismatch in Children's Weight Assessment, Ideal Body Image, and Rapidly Increased
      Obesity Prevalence in China: A 10-Year, Nationwide, Longitudinal Study.
AB  - OBJECTIVE: This study examined secular trends in children's weight-status
      assessment, measured weight status, and ideal body image and their associations
      with subsequent changes in BMI, and it explored the differences between
      sociodemographic groups in China. METHODS: Longitudinal data from the China
      Health and Nutrition Survey of 4,605 children aged 6 to 17 collected between 2000
      and 2011 were used and fitted to mixed models. RESULTS: From 2000 to 2011,
      overweight/obesity prevalence increased from 6.5% to 16.8%, but the percentage of
      children with self-perceived weight status as "fat" remained around 2.0%; 49.0%
      of children underestimated their weight status at baseline. Self-perceived body
      image of most participants was tracked during follow-up. Children who perceived
      themselves as being fat at baseline had a higher BMI increase over time during
      follow-up than those with an average body image (beta [SE] = 0.99 [0.14] kg/m2
      per year, P < 0.001). Boys, young children, recent cohorts, and rural children
      had higher BMI increases than their counterparts. Over time, the thin-body
      silhouette became more desirable (8.4 percentage points higher, P < 0.001).
      CONCLUSIONS: Chinese children experience a large incongruence between their
      weight-status assessment, ideal body image, and actual weight status. Health
      promotion programs should examine their role in assisting children in developing
      a healthy body image and gaining greater self-motivation toward promoting a
      healthy lifestyle.

PMID- 30281210
TI  - Maternal and Postnatal Supplementation of Fish Oil Improves Metabolic Health of
      Mouse Male Offspring.
AB  - OBJECTIVE: Over half of American women of childbearing age have either obesity or
      overweight. Hence, maternal programming through diet is critical for prevention
      of diseases in the offspring. Clinical trials with fish oil (FO) report various
      health benefits; however, it remains unclear whether maternal and postnatal
      consumption of FO protects offspring from adverse effects of consuming a high-fat
      (HF) diet. METHODS: Female mice were fed HF diets supplemented without (HF) or
      with FO from 8 weeks before pregnancy through lactation. A low-fat (LF) diet was
      included as a control diet. After weaning, male offspring from HF or FO dams were
      either continued on their respective diet (HF-HF and FO-FO) or switched to the
      other diet (HF-FO and FO-HF) and compared with LF. Phenotypic and mechanistic
      studies were performed. RESULTS: FO-FO offspring demonstrated significantly
      higher glucose clearance and insulin sensitivity compared with other pups fed the
      HF diet (P < 0.05). Furthermore, FO-FO pups had lower adiposity, inflammation,
      and fat deposition in the liver, consistent with reduced markers of hepatic
      lipogenesis and increased hepatic lipid oxidation. CONCLUSIONS: Supplementation
      of FO during pregnancy and early life is more beneficial than treating with FO
      either during pregnancy or in pups.

PMID- 30281211
TI  - Time to Be All Eyes and Ears When it Comes to Protective Eyewear.
AB  - Proper eyewear starts with making sure the PPE fits the task at hand. This often
      requires employers to conduct a workplace hazard assessment.

PMID- 30281212
TI  - Five-year outcomes of a personalized pro re nata treatment regimen with anti
      vascular endothelial growth factor for neovascular age-related macular
      degeneration.

PMID- 30281213
TI  - Frontiers in pigment cell and melanoma research.
AB  - In this perspective, we identify emerging frontiers in clinical and basic
      research of melanocyte biology and its associated biomedical disciplines. We
      describe challenges and opportunities in clinical and basic research of normal
      and diseased melanocytes that impact current approaches to research in melanoma
      and the dermatological sciences. We focus on four themes: (1) clinical melanoma
      research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic
      pigment cell research, with the goal of outlining current highlights, challenges,
      and frontiers associated with pigmentation and melanocyte biology. Significantly,
      this document encapsulates important advances in melanocyte and melanoma research
      including emerging frontiers in melanoma immunotherapy, medical and surgical
      oncology, dermatology, vitiligo, albinism, genomics and systems biology,
      epidemiology, pigment biophysics and chemistry, and evolution.

PMID- 30281215
TI  - CCL21 as a potential biomarker for pulmonary arterial hypertension in systemic
      sclerosis.
AB  - We thank Zhou and co-workers for their interest regarding our newly published
      manuscript on the role of CCL21 in pulmonary arterial hypertension (PAH)
      associated with systemic sclerosis (SSc). Here, we want to respond to their
      concerns. Genome-wide association studies (GWASs) have been foreshadowed to be a
      major advance in biomedical discovery, with many robust associations to complex
      diseases. However, although there are found polymorphisms with SSc, there are, to
      date, no existing genetic loci for SSc-PAH. Secondly, despite this success, GWAS
      studies have met considerable skepticism regarding their clinical applicability;
      mainly arising from their unclear functional consequences. This article is
      protected by copyright. All rights reserved.

PMID- 30281214
TI  - Development and validation of a model to predict tyrosine kinase inhibitor
      sensitive EGFR mutations of non-small cell lung cancer based on multi
      institutional data.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) with different EGFR mutation types
      shows distinct sensitivity to tyrosine kinase inhibitors (TKIs). This study
      developed a patho-clinical profile-based prediction model of TKI-sensitive EGFR
      mutations. METHODS: The records of 1121 Chinese patients diagnosed with NSCLC
      from November 2008 to October 2014 (the development set) were reviewed.
      Multivariate logistic regression was conducted to identify any association
      between potential predictors and the classic sensitive EGFR mutations (exon 19
      deletion and exon 21 L858R point mutation). A prediction index was created by
      assigning weighted scores to each factor proportional to a regression
      coefficient. Validation was made in an independent cohort consisting of 864
      patients who were consecutively enrolled between November 2014 and January 2017
      (the validation set). RESULTS: Seven independent predictors were identified:
      gender (female vs. male), adenocarcinoma (yes vs. no), smoking history (no vs.
      yes), N stage (N+ vs. N0), M stage (M1 vs. M0), brain metastasis (yes vs. no),
      and elevated Cyfra 21-1 (no vs. yes). Each was assigned a number of points. In
      the validation set, the area under curve of the prediction index appeared as
      0.698 (95% confidence interval 0.663-0.733). The sensitivity, specificity,
      positive and negative predictive values, and concordance were 95.0%, 32.3%,
      61.4%, 85.1%, and 65.6%, respectively. CONCLUSION: We developed a patho-clinical
      profile-based model for predicting TKI-sensitive EGFR mutations. Our model may
      represent a noninvasive, economical choice for clinicians to inform TKI therapy.

PMID- 30281217
TI  - CCL21: a potential biomarker for pulmonary arterial hypertension in Systemic
      Sclerosis? Comment on the article by Hoffmann-Vold et al.
AB  - We read with great interest the manuscript by Hoffmann-Vold et al, that was
      published in a recent issue of Arthritis & Rheumatology. They found that serum
      levels of CCL21 were significantly higher in Systemic Sclerosis (SSc) patients
      than controls, and elevated prior to pulmonary arterial hypertension (PAH)
      diagnosis. Moreover, CCL21 serum levels were positively correlated with the PAH
      and occurrence of PAH related events, which suggested the potential of CCL21 to
      serve as a promising marker for SSc-PAH risk prediction and PAH progression.
      However, we have three main concerns regarding using CCL21 as a serum biomarker
      of SSc-PAH. This article is protected by copyright. All rights reserved.

PMID- 30281216
TI  - Topotecan monotherapy for the treatment of relapsed small cell lung cancer in
      elderly patients: A retrospective analysis.
AB  - BACKGROUND: Topotecan is one of the most active chemotherapeutic drugs for small
      cell lung cancer (SCLC). However, its efficacy in elderly patients with SCLC has
      not been validated. This study evaluated the feasibility and efficacy of
      topotecan monotherapy in elderly patients with relapsed SCLC. METHODS: Between
      January 2000 and March 2017, 43 patients aged >= 70 years received topotecan
      monotherapy for relapsed SCLC at four institutions. The clinical outcomes and
      adverse events of treatment were retrospectively analyzed. RESULTS: Twenty-nine
      patients (median age 75 years; range: 70-83 years) had sensitive-type relapse,
      while 14 (median age 78 years; range: 71-82 years) had refractory relapse. The
      median number of treatment cycles was two (range: 1-6). The response rate was
      7.0% (10.3% and 0% in sensitive and refractory patients, respectively), while the
      disease control rate was 23.2% (20.6% and 42.8% in sensitive and refractory
      patients, respectively). Median progression-free survival was 1.9 months in
      sensitive patients and 1.4 months in refractory patients (P = 0.87). The median
      survival time from the start of topotecan therapy was 5.5 months in sensitive
      patients and 4.0 months in refractory patients (P = 0.64). Grade >= 3
      hematological toxicities were as follows: leukopenia, 37.2%; neutropenia, 51.1%;
      anemia, 0%; thrombocytopenia, 32.5%; and febrile neutropenia, 9.3%. No treatment
      related deaths occurred. CONCLUSION: Although hematological toxicities
      (particularly neutropenia) were severe, topotecan showed favorable disease
      control in both sensitive and refractory patients. Topotecan may thus be a
      preferred treatment for elderly patients with relapsed SCLC.

PMID- 30281218
TI  - [Prevention and treatment of Herpes Labialis].
AB  - Herpes labialis, more commonly known as cold sores or fever blisters, is the most
      common clinical manifestation of infection with Herpes simplex virus type 1. It
      is a highly contagious and widespread infection. Generally benign, cold sores may
      however disturb those who suffer from them, because of the symptoms they cause or
      their unsightly and frequent appearance. The pharmacist is often consulted to
      relieve cold sore recurrences. As for any request for advice, the pharmacist will
      assess if he can help the patient himself or if medical advice is more
      appropriate. Besides a possible symptomatic treatment, the pharmacist will also
      advise the patient to prevent recurrence and the contamination of other people.

PMID- 30281219
TI  - [Communication on smoking in community pharmacy. Results of a survey in Belgium].
AB  - For several reasons the community pharmacist plays an important role in smoking
      cessation. In order to know how he is fulfilling this role, a survey was
      conducted among Belgian community pharmacists on smoking cessation communication
      in their pharmacy. The pharmacists and the pharmacy personnel were invited to
      answer an online questionnaire. In community pharmacy the patient is quite often
      asked if he smokes, however there still remain some obstacles to talk with the
      patient about smoking behaviour. The major obstacles are lack of time and the
      fear of a conflict with the patient. The results of the survey reveal that
      pharmacists and their assistants have a good knowledge of smoking cessation, but
      there is still some room to improve. In order to improve the smoking cessation
      support by pharmacists and their assistants, some efforts are necessary to
      overcome the obstacles. It would also be useful to organise more courses of
      tabacology at the faculties of pharmacy of the universities and in the continuing
      education programs for pharmacists.

PMID- 30281220
TI  - [Stability of amiodarone hydrochloride in intravenous fluids with 5% glucose].

PMID- 30281221
TI  - Top Ten Facts You Should Know about "Alpha-gal, the Newly Described Delayed Red
      Meat Allergy.

PMID- 30281222
TI  - Assessment of Secondary Causes of Osteoporosis and Racial Differences in Men with
      Normal vs. Abnormal Bone Mineral Density in a Cohort of Men Undergoing Bone Mass
      Measurement.
AB  - Osteoporosis is a condition generally associated with olderwomen, but it is
      rapidly becoming a growing problem for males as well. Screening and treating men
      early is the only way to address this problem. The known demographic factors of
      osteoporosis in males such as age, race and BMI as well as secondary causes oflow
      bone mineral density (BMD) i.e. osteoporosis, have not been well examined in the
      actual practice settingbased on available literature. This study aims to describe
      the prevalence of the demographic factors and secondary causes in men with low
      BMD and also to assess their individual contribution to the overall prevalence. A
      retrospective chart review of 585 men who underwent bone density scan at the
      University of Mississippi Medical Center from 2005-2012 was performed. At the
      time of their scans, patients were also asked to complete a questionnaire
      assessing demographics, comorbidities, social factors, and medication use. The
      results suggest that racial difference and differences in secondary causes exist
      in the epidemiology of male osteoporosis, and this needs to be assessed further.
      The notion that African American males are protected from OP is unsupported in
      our data as well as the literature. Overall our research demonstrated that low
      BMI is the most important factor associated with low BMD in male patients.

PMID- 30281223
TI  - The Spice of Life...and Death: A Case Presentation and Review of Synthetic
      Marijuana Use in Mississippi.
AB  - Like cocaine and heroin before, SCs represent a major health risk to individuals.
      The ever-changing formulations ofSCs make them potentially more toxic, as
      manufactures attempt to skirt current drug laws. Catastrophic neurologic,
      cardiovascular and renal disease may result from SCs and other impurities
      packaged with these "herbal products". Ongoing education to the public about
      these hazardous drugs is needed to 'Combat the fact that they are sometimes
      promoted as safe and natural. The epidemic of SC use must be emphasized to
      Mississippi physicians to improve recognition of SC symptoms until a rapid
      detection assay is available.

PMID- 30281224
TI  - The Inaugural Address of the 149th President LEE VOULTERS, MD - 2016-17 MSMA
      PRESIDENT AUGUST 12, 2016 - HILTON JACKSON.

PMID- 30281225
TI  - [Bisacodyl as laxative in Belgian pharmacy].
AB  - Obstipation is a common complaint in pharmacies and one of the treatment
      strategies is the delivery of enteric coated bisacodyL tablets. This article
      reviews the different aspects that are important for pharmacists to guarantee
      patient safety: whether medical treatment is required or not, which advice should
      be given on how to use the drug, and to conclude what is the analytical quality
      of the commercial products on the Belgian market.

PMID- 30281226
TI  - [Medication counselling and support with individual medication preparation for
      trail elderly living at home-preliminary results].
AB  - Background Medication safety and adherence are important aspects of quality of
      life, especially for frail elderly in our society. However, many elderly living
      at home may experience difficulties when taking their medication, and are
      therefore at risk for medication- related problems. The current living lab was
      implemented within the framework of the Flanders Care Living Labs and set the
      objective to develop a care pathway to improve medication safety and adherence
      for elderly living at home. Automated Individual Medication Preparation [IMP] was
      provided by a community-pharmacist in order to support frail elderly in taking
      their medication more correctly and thereby improving adherence. Methods In a
      before and after study, each patient was supported for 13 weeks through a
      multidisciplinary care pathway. Key in this pathway was the shared medication
      schedule (between GP and pharmacist) as the starting point for IMP and medication
      counselling. The increased medication support based on IMP was evaluated in frail
      elderly (age a 65 years, complex medication scheme a 5 medicines and a 3 intakes
      / day) before and after the study, by measuring adherence and satisfaction with
      counselling and repackaging the medication in sachets. Results The preliminary
      results of the current study showed that the self-reported adherence rate in
      frail elderly was significantly higher (p <0.05) after implementation of the
      pharmacists' intervention with automated IMP. At the end of the study every
      patient indicated that the repackaging of the medication by dose was helpful in
      order to take their medication correctly. Conclusion Increased medication
      counselling with IMP by the community-pharmacist may be a useful aid and
      supporting tool for frail elderly living at home with a complex medication
      scheme.

PMID- 30281227
TI  - [Care pathway for high urinary tract infection: an update in an emergency
      department of a French military hospital].
AB  - Objectives Assessing the impact of professional practices on a patient's course
      is an interesting way to optimize health care pathway. The aim of our study is to
      update and evaluate the compliance to the recommendations of the Societe de
      Pathologie Infectieuse de Langue Francaise with regards to professional practices
      and the route of patients admitted to the emergency department of a French
      military hospital for high urinary tract infection. Patients and methods A
      retrospective study was carried out on patients admitted to the emergency
      department and treated for high urinary tract infection from January 1st, 2015 to
      April 30th, 2015. Clinical and administrative data, medical exams, and antibiotic
      prescriptions were extracted from computerized patient medical files and from
      emergency medical files. Results Out of 91 medical cares, 57% were compliant with
      the recommendations. For 60% of the patients, blood cultures were not argued and
      in 70% of cases, imaging wasn't justified. Antibiotic prescriptions were not
      compliant in 31% of cases, mostly due to long prescription durations. Two third
      of patients received outpatient care. All hospitalizations were argued.
      Conclusions Drawing up a caring protocol, regularly raising awareness to the good
      use of antibiotics, as well as reinforcing a cross disciplinary approach will
      allow optimizing health care pathways for patients coming to the emergency
      department with high urinary tract infection.

PMID- 30281228
TI  - [Standardisation of methods for dilution of intravenous medications in hospital].
AB  - Introduction The administration of intravenous medications in hospital is a
      common practice. Although it may seem almost insignificant, this practice remains
      no less an act which involves risks, due to many factors identified. It is
      therefore important to gather, clarify and communicate the updated information on
      the modalities of the administration of these injections in order to facilitate
      and secure the work of the teams of care with a view of an optimal and
      standardized administration of intravenous medications. Method The tables of
      standardization of injectable drugs have been made on several occasions in the
      past and distributed in the care units. The latest version of these documents was
      reviewed and updated in the light of the recent editions of several sources. The
      data concerning each individual injectable medicine have individual as well been
      systematically updates. The updated data have been integrated into the electronic
      prescription of medicines, a standardized dilution is now proposed by default to
      the prescriber. For some drugs, special modalities of administration have been
      planned to meet the specific needs of patients hospitalized in the Intensive Care
      Unit (ICU). Results The methods for dilution of injections in classical
      hospitalization have been integrated in the electronic prescribing software (238
      "packages" in total. The specific dilutions used in the ICU (48 in total, have
      been validated but may not be used in the conventional care units. Conclusion All
      of the information relating to the methods of preparation and administration have
      been gathered and clarified in order to facilitate and secure the work of the
      teams of care and thus enable optimal administration of intravenous medications.
      The information is accessible on paper file and via the internal computer
      network, the PC of intensive care units and the software Computerized
      prescription.

PMID- 30281229
TI  - [Essential oils: good advice by the pharmacist is necessary].
AB  - Essential oils are highly concentrated products of a complex composition,
      obtained from plants. Their therapeutic use relies mostly on tradition and
      experience. Often few clinical trials are available. The quality and efficacy of
      only several essential oils are described in the European pharmacopeia and in
      monographs of the EMA. In addition, essential oils on the Belgian market have
      different statutes [medicine, food supplement, raw material...]. This results in
      a complicated legislation. Furthermore, the general public wrongly assumes that
      essential oils, because of their vegetal origin, can be used at any time without
      any danger. However, toxicological reactions are described after oral, topical
      and other routes of administration. Certain precautions need to be taken before
      using potentially hazardous essential oils. Children and pregnant women are
      particularly vulnerable populations that need extra attention.

PMID- 30281230
TI  - [Practical guidelines to ensure the quality of compounded preparations in
      community pharmacies].
AB  - Compounded preparations are an additional therapeutic option besides registered
      medicines. Because of their <<tailor made therapy>> they have a great value and
      thus an undeniable place in the therapeutic arsenal available to the physician.
      To maintain this position, however, they must be of unquestionable quality.
      Structuring and documenting the compounding operations, incorporating the
      necessary controls and respect for evident basic rules and precautions can reduce
      potential errors to a minimum. Pharmacists can rely for this on existing
      recommendations listed in the different reference books such as the Therapeutic
      Magistral Form and the Guidelines for Good Officinal Practices, but which aren't
      always commonly used by pharmacists.

PMID- 30281231
TI  - [Pharmaceutical care for pediatric hemato-oncology and stem cell transplantation
      patients. Inventory of experiences and needs].
AB  - Introduction Pharmacists can be faced with pediatric patients treated for a
      hemato-oncological condition or patients who underwent a hematopoietic stem cell
      transplantation [HSCT). This study aims to identify the roLe of the pharmacist
      and master in pharmacy students as well as their knowLedge of pharmaceutical care
      for this specific patient population. In addition, their experiences of basic
      education and expectations of continued education in pediatric hemato-oncology
      and HSCT are analyzed. Methods Pharmacists in Flanders and pharmacy students
      [Ghent University] were requested to complete and online survey with (1) general
      questions, (2) questions about knowledge by means of theoretical examples and
      practical cases and (3) questions about education (past and future) related to
      this topic. Results A total of 156 pharmacists and 67 students completed the
      survey. Results demonstrated that 22.0% of pharmacists and students already
      delivered medication to this particular patient group. A total of 98.2%
      [pharmacists and students] found that they had insufficient knowledge and
      experience to give optimal pharmaceutical advice. The pharmacist scored only
      34.0% [average] in the general knowledge section, students 44.0%. Both
      pharmacists [68.6%] and students [79.0%] agreed that this topic should be
      included in the basic curriculum. The vas majority [91.0% pharmacists, 89.6% of
      students] were asking for courses on this theme by means of and evening session
      or an e-learning tool. Conclusion Although the role of pharmacists and students
      in this patient group can be confirmed, the results of the survey demonstrate a
      lack of knowledge among pharmacists and students about pediatric hemato-oncology
      and HSCT. There is interest in education in the basic curriculum and the vast
      majority of pharmacists are interested in continuing education.

PMID- 30281232
TI  - [The social sciences at the Faculty of Pharmacy: and innovative course of
      community health at the University of Montreal].
AB  - Social sciences are important for training in pharmacy faculties. The course set
      up at the Faculty of Pharmacy of the University of Montreal in 2011 is a very
      innovative way to meet this challenge. The purpose of this report is to share
      this experience by providing a synthetic description. Many students were able to
      develop new skills and strengthen their skills, including leadership and critical
      thinking. The Faculty of Pharmacy was also able to achieve greater visibility in
      the Montreal community, that is to say from the associations, but also with what
      is out there called the "local health network" linking various health care
      professionals and institutions. Beyond the quantifiable results, this course is
      an evolving learning process in which the group interactions, individual and
      collective values and the task sharing allow students to build a working
      knowledge of social factors, which d.etermine health problems.

PMID- 30281233
TI  - Tetemedicine in Mississippi: Can It Improve Our Last Place in Health?.

PMID- 30281235
TI  - "I'm coughing up blood".
AB  - An 18-year-old female presents with acute hemoptysis and rapidly deteriorates
      into fulminant pulmonary and renal failure. She is ultimately diagnosed with
      microscopic polyangiitis with pauci- immune glomerulonephritis. This case report
      will delineate her presentation, work-up, broad differential diagnosis, and
      outcome.

PMID- 30281234
TI  - Reducing Barriers to 17-Hydroxprogestrone Caproate (17P) Injections to Prevent
      Recurrent Preterm Birth in Mississippi.

PMID- 30281236
TI  - Ten Things You Want to Know about Vaccines for Adults.

PMID- 30281237
TI  - Child Abuse & Neglect in Mississippi: Beginning the Conversation.
AB  - The Mississippi State Medical Association House of Delegates passed Resolution 18
      in 2016 to bring attention to child abuse and neglect in Mississippi. This
      descriptive article is the first of a number of articles that will be included in
      the Journal MSMA to educate further the medical community on a problem that
      impacts individuals throughout their life. Research has shown that our medical
      professionals, just like many other disciplines that encounter child abuse, are
      unprepared to identify and respond to the issue of child abuse. This article
      outlines the magnitude of child abuse in Mississippi as well as the life-long
      ramifications of that abuse. Lastly, this article outlines two current
      initiatives in Missis'sippi attempting to make systemic changes to identification
      and response to cases of child abuse.

PMID- 30281238
TI  - [Polymedication among elderly patients Preventing drug related problems and
      inappropriate medication].
AB  - Polypharmacy is a common phenomenon among elderly patients. A simultaneous intake
      of a large number of drugs can possibly lead to drug-related problems due to an
      increased risk of drug interactions, medication errors, contra-indications, but
      also a lack of patient compliance. Elderly patients are particularlyvulnerable
      because of physiological and pathological aging. Therefore we need to be
      particularly attentive to their medication, especially in case of polypharmacy. A
      systematic review of the medication for elderly patients should regularly be
      performed to prevent the occurrence of potentially drug-related problems. In view
      of his central role in the dispensing of medicines, the pharmacist can carry out
      this medication review in consultation with the treating physician.

PMID- 30281239
TI  - [Capsaicinoids, capsaicin and capsicum oleoresin].

PMID- 30281240
TI  - [Reliability of OTC advertisement Relevance and quality of cited literature].
AB  - Introduction Pharmacist receive a lot of publicity for OTC products. Often one or
      more literature references are mentioned to support the advertising claims.
      Objective In this study we examine: [1) whether the advertising claim is
      consistent with what is stated in the literature references mentioned on the
      leaflet and [2] whether these literature references are trustworthy. Method
      Through 60 randomly selected community pharmacies, pharmacist-directed
      advertisements for OTC products I= medicines, medical devices, dietary
      supplements and parapharmacy) with at least one bibliographic reference, were
      collected. The literature references listed in these leaflets were assessed in
      terms of content [= is the claim consistent with the information in the
      reference) and technically [= evaluation of the quality of the references].
      Results The 85 collected OTC advertisements made 214 claims that referred to 243
      references. Of these, 128 references did not support the promotional claim. The
      remaining 84 references did support the corresponding claim. From 31 references
      no full text was obtained. Of the 84 supporting references 44 were of dubious
      quality. The remaining 40 references were found to be reliable. Conclusion This
      study shows that the literature references in advertising leaflets for OTC
      products are not a reliable source of information on the advertised product.
      Pharmacists should deal critically with this information and should be encouraged
      to consult reliable scientific sources.

PMID- 30281241
TI  - [A practical program for outpatient parenteral antimicrobial therapy].
AB  - Some infections require prolonged parenteral antimicrobial therapy, which can be
      continued in an outpatient setting. The Ghent University Hospital has fifteen
      years of experience with Outpatient Parenteral Antimicrobial Therapy [OPAT) in
      the patient own home setting. As a quality improvement initiative, this process
      was critically reviewed in a multidisciplinary approach. Several challenges and
      barriers were identified, including regulatory obstacles for OPAT in Belgium,
      such as Lack of uniformity in ambulatory reimbursement of parenteral
      antimicrobials. There is no financial incentive for the patient with OPAT, as
      costs for the patient of outpatient therapy can be higher as compared with
      hospitalization. Other barriers include delayed approval of the certificate for
      reimbursement, low availability of medicines in the community pharmacies and
      limited knowledge of the medical devices for administration in ambulatory
      setting. All critical steps in the revised OPAT program are summarized in a
      flowchart with a checklist for all stakeholders. Firstly, a list with specific
      criteria to include patients in an OPAT program is provided. Secondly, the
      Multidisciplinary Infection Team received a formal mandate to review all eligible
      OPAT patients. In order to select the most appropriate catheter a decision tree
      was developed and standardized packages with medical devices were developed.
      Thirdly, patients receive oral and written information about the treatment with
      practical and financial implications. Fourthly, information is provided towards
      the general practitioners, community pharmacists and home care nurses.
      Standardization of the OPAT-program aims at improving quality and safety of
      intravenous antimicrobial therapy in the home setting.

PMID- 30281242
TI  - [Frequency and nature of drug related problems with corticosteroids in Belgian
      community pharmacies].
AB  - Aim Aims are: 1] Identify causes of Drug Related Problems (DRPs), interventions
      performed by pharmacists and results of corticosteroid- related problems and 2]
      distinguish between problems related to inhaled and general corticosteroids.
      Methods During 5 days of their internship, 534 final year students of
      pharmaceutical sciences in six Belgian universities collected DRPs encountered in
      community pharmacies, as well as related interventions performed by pharmacists
      and the result of the intervention. The DRPs' electronic registration was done
      through an adapted tool for Belgium based on the classification of Pharmaceutical
      Care Network Europe [PCNE- v 6.2]. Findings The frequency of DRPs is 24,8%. 766
      DRPs (4,8%) related to corticosteroids, of which 351 were inhaled
      corticosteroids. The most common causes of corticosteroid-related problems (53-
      59%) were technical causes. The most represented category of clinical causes was
      the inappropriate choice of drug [33-41%]. Pharmacists' intervention was similar
      for inhaled and general corticosteroids. Pharmacists intervened orally with
      patients in 38-40% of total interventions, and in writing in 16% of
      interventions. Pharmacists did not react in 16% of corticosteroid-related
      problems. 81-83% of PLMS were resolved partially or completely. Conclusion In
      conclusion, DRPs detected in community pharmacies related to corticosteroid are
      infrequent (4,8% of DRPs) but 82% of detected problems have been resolved.
      Furthermore, the study shows the importance for the Belgian health system to
      introduce an official DRPs classification and software facilitating their
      documentation in community pharmacies.

PMID- 30281243
TI  - [Medication screening by the community pharmacist in Belgium].
AB  - About 20% of the European population is older than 65 years. Because of
      multimorbidity (i.e. multiple chronic condition within a patient), older patients
      are often prescribed multiple drugs [i.e. polypharmacy). Both older age and
      polypharmacy significantly increase the risk for adverse drug events.
      International research showed that more or less 5% of all unplanned hospital
      admissions is related to the use of medication. About 70% of these drug related
      admissions happened in patients older than 65 years. Moreover, about half of the
      admissions could have been avoided. These preventable hospital admissions were
      caused by the intake of medication without an indication, problems with
      medication adherence, interactions and/or insufficient monitoring. We define this
      as (potential Drug Related Problems [DRPI. DRPs can occur on multiple occasions
      during the medication management process: prescribing, dispensing, intake and
      monitoring. When DRPs can be detected in an early stage, significant consequences
      can be avoided. To accomplish this, multiple strategies are possible. One of the
      possibilities is performing a periodic medication screening by the community
      pharmacist in patient groups at risk. During such a medication screening, the
      pharmacotherapy is critically evaluated in a systematic and structured way. The
      implementation of medication screening in first-line health care is currently
      limited. The community pharmacist is nevertheless ideally placed to perform this
      task. There is an important relation of trust between him and the patient and the
      community pharmacist has access to a full medication history. Furthermore, as an
      expert in drug-related issues, he possesses all necessary knowledge to perform
      the pharmacotherapeutic analysis.

PMID- 30281244
TI  - [Drug-drug interactions with risk of QT-prolongation. A epidemiological study in
      Belgian community pharmacies].
AB  - Introduction Community pharmacists have an important role in the management of
      drug-drug interactions (DD). One of the interactions that can lead to serious
      adverse drug events, more specifically Torsade de Pointes and sudden cardiac
      death, are DDI with risk of CT-prolongation. Many drugs from different
      therapeutic classes have been linked with the risk of QT-prolongation (as listed
      in the QT-drug lists of CredibleMeds]. Moreover, patient-specific risk factors
      should be taken into account. This leads to a complex risk estimation of QT
      prolongation for each patient. Aim The aim of this study is to investigate the
      prevalence of DDI and the management of these interactions in community
      pharmacies, with special attention for DDI with a risk of QT-prolongation. Method
      This epidemiological study is based on data of an interuniversity, observational
      study in 534 Belgian community pharmacies with a last-year pharmacy student
      (November 2012 - March 2013), in which all drug-related problems (DRP) and
      associated interventions of the pharmacist were registered for drugs on
      prescription. In this study, all DRP that were registered as a DDI were selected.
      The evidence for these DD was verified in four information sources (DelphiCare,
      Medscape, Drugs.com, handbook 'Commentaren Medicatiebewaking'). Finally, an in
      depth analysis was performed for DDI with risk of QT-prolongation. QT-prolonging
      drugs were identified with the QT-drug lists of CredibleMeds. Results In total,
      64.962 prescriptions and 15.952 DRP were registered in the interuniversity study,
      of which 1858 DRP (11.6%) described as a DDI that was confirmed in at least one
      of the information sources. Of these interactions, 223 [12.0%] were linked with a
      risk of QT- prolongation. The majority of the concerned drugs are situated in
      list 1 of CredibleMeds (known risk of Torsade de Pointes). In 69 CT-prolonging
      DDI, two drugs of list 1 were involved. The most frequent QT-prolonging DDI was
      between escitalopram and quetiapine (N=11J. In 69.5% of the QT-prolonging DDI, an
      intervention was performed by the community pharmacist. In 47.8% of these
      interventions, the DDI was discussed with the patient. In 28.3% of the QT
      prolonging DDI, the pharmacist contacted the physician. However, the proposed
      intervention was often considered unnecessary by the physician (42.9%). In only
      4.5% of the interventions, the involved CT-prolonging drug was replaced by an
      alternative. Conclusion DDI represent an important part of the DRP in community
      pharmacies, including DDI with a risk of CT-prolongation (12% of the
      interactions). In the majority of the QT-prolonging DDI, at least one QT
      prolonging drug of list 1 of CredibleMeds [known risk of Torsade de Pointes) was
      involved. In only 4.5% of the interventions, the involved QT-prolonging drug was
      replaced by an alternative.

PMID- 30281245
TI  - [Biosimilars, no generic biologicals!].
AB  - Biologicals are omnipresent in the current therapeutic arsenal for treating
      several chronic and life-threatening diseases. Following expiry of patent,
      'generic' versions of biological medicines are being developed, so-called
      biosimilars. In view of their potential to reduce the continuous economic
      pressure of biologicals on the healthcare system, the eagerness to introduce them
      at fast rate as alternative treatment options is huge. For all parties involved
      (patients, physicians, pharmacists and other healthcare professionals), it is of
      utmost importance to get acquainted with the features of biosimilars. Biosimilars
      differ from generic drugs as they are, as a result of a complex production
      process in living organisms, never 100% chemically identical to the originator
      drug. However, the stringent regulatory pathway for approval requires similarity
      to the reference biological medicine in terms of biological activity, safety and
      efficacy. Knowledge on immunogenicity, interchangeability and substitution is
      constantly evolving. As more biosimilars - possibly of the same reference
      biological - will entrance the market, traceability becomes key for an efficient
      pharmacovigilance system. Pharmacists, in their role to advice and support
      patients, should be adequately trained and have access to relevant information
      about all aspects on biosimilars.

PMID- 30281246
TI  - [Evaluation of preoperative nutritional status in visceral surgery Correlational
      study].
AB  - Objective Is to evaluate the nutritional status of preoperative patients in the
      visceral surgery department III of CHU Ibn Rushd of Casablanca and to correlate
      to postoperative length of stay. Patients and methods Prospective observational
      study of six months from February 2015 to late July 2015, in patients from being
      operated in the visceral surgery department II1. The nutritional status of 151
      patients preoperatively was evaluated the correlation between the various
      diagnostic tests and clinical and biological parameters was investigated and
      postoperative length of stay was calculated. Results 151 patients predominantly
      female (72.84%1, reporting their consent, were selected for this study. 51.56% of
      patients had risk factors for undernutrition. The cholelithiasis was the most
      responded diagnosis (57.61%). The Nutritional Risk Index (NRII allowed to
      identify 13 low nutritional risk patients, 7 moderate-risk and 3 major risk.
      According to the Mini Nutritional Assessment (MNA two elderly people [over 70
      years] were at risk of undernutrition and one person had a bad nutritional
      status. Nutritional risk stratification identified 19 patients with postoperative
      nutritional grade 3. The average length of stay was variable; it was not
      correlated with the nutritional status of patients against it is based on the
      type of surgery. Conclusion The risk of undernutrition was high; however, a
      single parameter is insufficient for the diagnosis of preoperative
      undernutrition, a combination of different parameters would be a more reliable
      method.

PMID- 30281247
TI  - Taking a Holistic Approach to Lab Safety.
AB  - OSHA has required employers to develop a Chemical Hygiene Plan that addresses
      labeling as well as all other aspects of the Laboratory standard.

PMID- 30281248
TI  - Impact: Developing an Attitude for Safety.
AB  - If workers are overly optimistic that no injuries will befall them, they may be
      more likely to take risks that could end up in injuries.

PMID- 30281249
TI  - How Cooling Boosts Productivity.
AB  - Training and company policies must help employees decide that they can protect
      themselves from heat stress. Reducing heat stress will improve productivity and
      reduce accidents in the workplace.

PMID- 30281250
TI  - Can an Industrial Vacuum Solve Confined Space Hazards?
AB  - From grain handling operations to heavy blast material, pit cleaning with vacuums
      allows workers to clean outside of confined space.

PMID- 30281251
TI  - Formula for Improving Safety Culture.
AB  - Good or bad, you have already created a safety culture.

PMID- 30281252
TI  - Preventing Strained Communications.
AB  - Strong communications are critical to supporting, guiding, and influencing; a
      leader's connections with others heighten the ability to influence, as well as
      quantity and quality of work performance.

PMID- 30281253
TI  - Checking the Safety of Closed system Transfer Devices.
AB  - The Nov. 7 meeting allows NIOSH personnel to give an update of new protocol
      developments.

PMID- 30281254
TI  - Prescription Safety Eyewear: Style, Design, Ergonomics, Delivery.
AB  - Glasses are more protective, resilient, and fashionable than ever before.

PMID- 30281255
TI  - Making Sense of a Safety Data Sheet.
AB  - According to OSHA, employers must ensure that Safety Data Sheets are readily
      accessible to employees for all hazardous chemicals in their workplace, and
      employees should have immediate access to the information without leaving their
      work area when needed, even during a power outage or other emergency.

PMID- 30281256
TI  - Residual Confined Space Hazards...An Unintended Booby Trap!
AB  - Using elements of the new construction industry regulation for confined spaces in
      a general industry program will go a long way to save the lives of those who
      would otherwise fall victim to them.

PMID- 30281257
TI  - Peer-to-Peer Wireless: A Game Changer for Confined Space Monitoring.
AB  - New advances in gas detection equipment take real-world scenarios to heart and
      ensure everyone working around confined spaces will know where and why
      instruments are alarming.

PMID- 30281258
TI  - Selecting Appropriate Respirators--A Complicated Matter.
AB  - When respiratory hazards cannot be eliminated and employers are considering using
      respiratory protection, choosing the right respirator is the key.

PMID- 30281259
TI  - Harnessing the Powered Air Purifying Respirator.
AB  - Differentiating between contaminants that are gaseous or dust can be crucial in
      ensuring your PAPR is the proper PAPR.

PMID- 30281260
TI  - Understanding Rotating Shift Workers' Health Risks.
AB  - Until we know more, it is recommended that lighting in health care facilities
      should be designed to minimize acute melatonin suppression in night shift
      workers.

PMID- 30281261
TI  - Your Ambulance Service: Friend or Foe?
AB  - Strive for consistency to avoid confusion when emergencies occur. Debrief and
      analyze how an emergency was handled and whether the appropriate transport style
      had been used.

PMID- 30281262
TI  - What You Need to Know About Prescription Painkillers and Safety Risks.
AB  - The low number of employers who offer training about workplace usage of
      prescription drugs must increase dramatically.

PMID- 30281263
TI  - Selecting the Best Hand Protection for the Task.
AB  - When the correct level of persistence is applied toward identifying the hazard
      exposures, true cost savings will be seen every time.

PMID- 30281264
TI  - Why Quality Manufacturing Matters.
AB  - Get a grip on safety with new single-use glove technologies.

PMID- 30281265
TI  - How Fall Protection Has Changed Dramatically Over the Decades.
AB  - Given all we know and the resources available to us, "rescue" today should be
      viewed as an expected event with a positive outcome.

PMID- 30281266
TI  - Slip Resistance.
AB  - To date no study has been performed that defines the safe threshold COF for a
      specific tribometer for all combinations of footwear, contaminant, and floor
      type.

PMID- 30281268
TI  - 3 E's For Steering Superior Safety.
AB  - Enlist these three critical, interlocking "E's" in your own way and you'll also
      achieve remarkable strides in Safety performance, communications, leadership, and
      culture.

PMID- 30281267
TI  - Oxidizer Selection and Technology Options.
AB  - As thermal oxidizer technologies have been applied to a wider range of industrial
      applications, new challenges are continually uncovered that test their efficacy
      and durability.

PMID- 30281269
TI  - Embracing the Safety Stand-Down's Message.
AB  - OSHA's construction industry fall protection standard, 29 CFR 1926.501, was its
      most-cited standard during fiscal year 2015, and construction standards for safe
      use of scaffolding and ladders also ranked among OSHA's Top Ten that year.

PMID- 30281270
TI  - On the Move.

PMID- 30281271
TI  - Safe Access to Any Space.
AB  - A variety of low-level access machines and aerial work platforms safely put jobs
      within reach.

PMID- 30281272
TI  - Welding Safety Best Practices.
AB  - Welders must be protected from electric shock, welding fumes, fire, and injuries
      that can be caused by insufficient PPE.

PMID- 30281273
TI  - Understanding the Modern Single Use Glove.
AB  - Glove construction now takes into account long-term usability to reduce finger
      fatigue, chronic skin conditions, and more troublesome musculoskeletal disorders.

PMID- 30281274
TI  - Flexible Peptide Linkers Enhance the Antimicrobial Activity of Surface
      Immobilized Bacteriolytic Enzymes.
AB  - Chemical linkers are frequently used in enzyme immobilization to improve enzyme
      flexibility and activity, whereas peptide linkers, although ubiquitous in protein
      engineering, are much less explored in enzyme immobilization. Here, we report
      peptide-linker-assisted noncovalent immobilization of the bacteriolytic enzyme
      lysostaphin (Lst) to generate anti- Staphylococcus aureus surfaces. Lst was
      immobilized through affinity tags onto a silica surface (glass slides) and nickel
      nitrilotriacetic acid (NiNTA) agarose beads via silica-binding peptides (SiBPs)
      or a hexahistidine tag (His-tag) fused at the C-terminus of Lst, respectively. By
      inserting specific peptide linkers upstream of the SiBP or His-tag, the
      immobilized enzymes killed >99.5% of S. aureus ATCC 6538 cells (108 CFU/mL)
      within 3 h in buffer and could be reused multiple times without significant loss
      of activity. In contrast, immobilized Lst without a peptide linker was less
      active/stable. Molecular modeling of Lst-linker-affinity tag constructs
      illustrated that the presence of the peptide linkers enhanced the molecular
      flexibility of the proximal Lst binding domain, which interacts with the
      bacterial substrate, and such increased flexibility correlated with increased
      antimicrobial activity. We further show that Lst immobilized onto NiNTA beads
      retained the ability to kill ~99% of a 108 CFU/mL microbial challenge even in the
      presence of 1% of a commercial anionic surfactant, C12-14 alcohol EO 3:1 sodium
      sulfate, when the Lst construct contained a decapeptide linker containing
      glycine, serine, and alanine residues. This linker-assisted immobilization
      strategy could be extended to an unrelated lytic enzyme, the endolysin PlyPH, to
      target Bacillus anthracis Sterne cells either in buffer or in the presence of
      anionic surfactants. Our approach, therefore, provides a facile route to the use
      of antimicrobial enzymes on surfaces.

PMID- 30281275
TI  - Assessing Substitution Effects on Surface Chemistry by in Situ Ambient Pressure X
      ray Photoelectron Spectroscopy on Perovskite Thin Films, BaCe xZr0.9- xY0.1O2.95
      ( x = 0; 0.2; 0.9).
AB  - Performance of proton-solid oxide fuel cells (H+-SOFC) is governed by ion
      transport through solid/gas interfaces. Major breakthroughs are then
      intrinsically linked to a detailed understanding of how parameters tailoring bulk
      proton conductivity affect surface chemistry in situ, at an early stage. In this
      work, we studied proton and oxygen transport at the interface between H+-SOFC
      electrolyte BaCe xZr0.9- xY0.1O2.95 ( x = 0; 0.2; 0.9) thin films and the gas
      (100 mTorr of H2O and O2) by using synchrotron-based ambient pressure X-ray
      photoelectron spectroscopy at operating temperature (>400  degrees C). We
      developed highly textured BaCe xZr0.9- xY0.1O2.95 epitaxial thin films, which
      exhibit high level of in-plane proton conductivity, that is, up to 0.08 S cm-1 at
      500  degrees C for x = 0.9. Upon applying 100 mTorr water partial pressure above
      300  degrees C, major changes are observed only in the O 1s and Y 3d core level
      spectra, with a clear Zr/Ce ratio dependency. OH- formation is favored by Ce
      content while initiated near Y. Hydration is also associated with surface
      secondary phase growth comprising oxygen-under-coordinated yttrium and/or yttrium
      hydroxide. With BaCe0.2Zr0.7Y0.1O2.95, high levels of ionic conductivities and
      chemical stability are obtained as a result of the optimized surface reaction
      kinetics, with low activation energy barrier for proton transport while
      restraining formation of OH-/SO42- adsorb species.

PMID- 30281276
TI  - Unidirectional Enhanced Emission from 2D Monolayer Suspended by Dielectric Pillar
      Array.
AB  - Monolayers of transition metal dichalcogenides show great promise for
      optoelectronic devices as atomically thin semiconductors. Although dielectric or
      metal nanostructures have been extensively studied for tailoring and enhancing
      emission from monolayers, their applications are limited because of the mode
      concentrating inside the dielectric or the high optical losses in metals,
      together with the low quantum yield in monolayers. Here, we demonstrate that a
      metal-backed dielectric pillar array can suspend monolayers to increase the
      radiative recombination, and simultaneously, create strongly confined band-edge
      modes on surface directly accessible to monolayers. We observe unidirectional
      enhanced emission from WSe2 monolayers on polymer pillar array.

PMID- 30281277
TI  - Cost-Effective, Wireless, Portable Device for Estimation of Hexavalent Chromium,
      Fluoride, and Iron in Drinking Water.
AB  - The quality of drinking water often remains unknown to people because of the
      inadequacy of cost-effective testing systems that can be used in the field. Major
      portable instruments for water-quality analysis include ion-selective electrodes
      (ISE) or colorimeters. These are low-cost devices, but in the case of multiple
      analyte detection, such as that of hexavalent chromium (Cr), fluoride (F-), and
      iron (Fe), with a single instrument, no portable systems are available, to the
      authors' knowledge. In this paper, we demonstrate the use of a low-cost
      (approximate price of INR 1500 or US$20), portable colorimetric system that can
      be operated with Android smartphones wirelessly to estimate the contamination
      levels of Cr(VI), F-, and Fe in drinking water. This system also generates
      absorption spectra by recording the absorbance of the analyte using a light
      dependent-resistor (LDR) sensor. An Android-application software named Spectruino
      was developed to calculate the concentrations of the analytes. We strongly
      believe that this cost-effective, portable system will be very useful in
      improving human health by ensuring drinking-water quality throughout India.

PMID- 30281279
TI  - Ion Mobility-Mass Spectrometry Using a Dual-Gated 3D Printed Ion Mobility
      Spectrometer.
AB  - Described herein is the development of a 3D-printed drift-tube ion mobility
      spectrometer (IMS) which operates in the open air and is capable of being coupled
      to any mass spectrometer. The IMS possesses one electrospray focusing electrode,
      31 drift electrodes with 7 mm inner diameters, and 2 ion gates at opposite ends
      of the IMS, totaling 109 mm in length. The second ion gate was timed with respect
      to the first ion gate to transmit portions of the separating ion packets to the
      MS at specified time intervals. By scanning the second ion gate and acquiring
      mass spectra during each time interval, we reconstructed ion mobility chronograms
      using mass spectra. Resolving powers of up to 45 were acquired using
      tetraalkylammonium cations. Separation is also demonstrated for solutions of
      amphetamines, opioids (fentanyls/fentanils), and bradykinin and angiotensin II.
      The highest mobility resolving powers were obtained when the injection times of
      the first and second ion gates were 0.3 and 1.0 ms, respectively. Experiments
      were performed on both an ion trap and triple quadruple mass analyzer to showcase
      the adaptability of the plastic IMS. Insights were gained into how ions separate
      in the open air compared to vacuum conditions with pure gas.

PMID- 30281278
TI  - Ultrathin Trilayer Assemblies as Long-Lived Barriers against Water and Ion
      Penetration in Flexible Bioelectronic Systems.
AB  - Biomedical implants that incorporate active electronics and offer the ability to
      operate in a safe, stable fashion for long periods of time must incorporate
      defect-free layers as barriers to biofluid penetration. This paper reports an
      engineered material approach to this challenge that combines ultrathin,
      physically transferred films of silicon dioxide (t-SiO2) thermally grown on
      silicon wafers, with layers of hafnium oxide (HfO2) formed by atomic layer
      deposition and coatings of parylene (Parylene C) created by chemical vapor
      deposition, as a dual-sided encapsulation structure for flexible bioelectronic
      systems. Accelerated aging tests on passive/active components in platforms that
      incorporate active, silicon-based transistors suggest that this trilayer
      construct can serve as a robust, long-lived, defect-free barrier to phosphate
      buffered saline (PBS) solution at a physiological pH of 7.4. Reactive diffusion
      modeling and systematic immersion experiments highlight fundamental aspects of
      water diffusion and hydrolysis behaviors, with results that suggest lifetimes of
      many decades at physiological conditions. A combination of ion-diffusion tests
      under continuous electrical bias, measurements of elemental concentration
      profiles, and temperature-dependent simulations reveals that this encapsulation
      strategy can also block transport of ions that would otherwise degrade the
      performance of the underlying electronics. These findings suggest broad utility
      of this trilayer assembly as a reliable encapsulation strategy for the most
      demanding applications in chronic biomedical implants and high-performance
      flexible bioelectronic systems.

PMID- 30281280
TI  - Proteins as Sustainable Building Blocks for the Next Generation of Bioinorganic
      Nanomaterials.

PMID- 30281281
TI  - Radial Growth Evolution of InGaAs/InP Multi-Quantum-Well Nanowires Grown by
      Selective-Area Metal Organic Vapor-Phase Epitaxy.
AB  - III-V semiconductor multi-quantum-well nanowires (MQW NWs) via selective-area
      epitaxy (SAE) is of great importance for the development of nanoscale light
      emitting devices for applications such as optical communication, silicon
      photonics, and quantum computing. To achieve highly efficient light-emitting
      devices, not only the high-quality materials but also a deep understanding of
      their growth mechanisms and material properties (structural, optical, and
      electrical) are extremely critical. In particular, the three-dimensional growth
      mechanism of MQWs embedded in a NW structure by SAE is expected to be different
      from that of those grown in a planar structure or with a catalyst and has not yet
      been thoroughly investigated. In this work, we reveal a distinctive radial growth
      evolution of InGaAs/InP MQW NWs grown by the SAE metal organic vapor-phase
      epitaxy (MOVPE) technique. We observe the formation of zinc blende (ZB) QW discs
      induced by the axial InGaAs QW growth on the wurtzite (WZ) base-InP NW and
      propose it as the key factor driving the overall structure of radial growth. The
      role of the ZB-to-WZ change in the driving of the overall growth evolution is
      supported by a growth formalism, taking into account the formation-energy
      difference between different facets. Despite a polytypic crystal structure with
      mixed ZB and WZ phases across the MQW region, the NWs exhibit high uniformity and
      desirable QW spatial layout with bright room-temperature photoluminescence at an
      optical communication wavelength of ~1.3 MUm, which is promising for the future
      development of high-efficiency light-emitting devices.

PMID- 30281283
TI  - Response to Comment on "Wavelength-Resolved Photon Fluxes of Indoor Light
      Sources: Implications for HO x Production".

PMID- 30281282
TI  - Structure-Activity Analysis of N-Type Calcium Channel Inhibitor SO-3.
AB  - As an omega-conopeptide originally discovered from Conus striatus, SO-3 contains
      25 amino acid residues and three disulfide bridges. Our previous study has shown
      that this peptide possesses potent analgesic activity in rodent pain models
      (mouse and rat), and it specifically inhibits an N-type calcium ion channel
      (Cav2.2). In the study presented here, we investigated the key amino acid
      residues for their inhibitory activity against Cav2.2 expressed in HEK 293 cells
      and analgesic activity in mice. To improve the inhibitory activity of SO-3, we
      also evaluated the effects of some amino acid residues derived from the
      corresponding residues of omega-peptide MVIIA, CVID, or GVIA. Our data reveal
      that Lys6, Ile11, and Asn14 are the important functional amino acid residues for
      SO-3. The replacement of some amino acid residues of SO-3 in loop 1 with the
      corresponding residues of CVID and GVIA improved the inhibitory activity of SO-3.
      The binding mode of Cav2.2 with SO-3 amino acids in loop 1 and loop 2 may be
      somewhat different from that of MVIIA. This study expanded our knowledge of the
      structure-activity relationship of omega-peptides and provided a new strategy for
      improving the potency of Cav2.2 inhibitors.

PMID- 30281284
TI  - Anisotropic Near-Zero Thermal Expansion in REAg xGa4- x ( RE = La-Nd, Sm, Eu, and
      Yb) Induced by Structural Reorganization.
AB  - In this work, we have discovered the anisotropic near-zero thermal expansion
      (NZTE) behavior in a family of compounds REAg xGa4- x ( RE = La-Nd, Sm, Eu, and
      Yb). The compounds adopt the CeAl2Ga2 structure type and were obtained as single
      crystals in high yield by metal flux growth technique using gallium as active
      flux. Temperature-dependent single crystal X-ray diffraction suggests that all
      the compounds exhibit near zero thermal expansion along c direction in the
      temperature range of 100-450 K. Temperature-dependent X-ray absorption near-edge
      spectroscopic study confirmed ZTE behavior is due to the geometrical features
      associated within the crystal structure. The anisotropic NZTE behavior was
      further established by anisotropic magnetic measurements on selected single
      crystals. The atomic displacement parameters, apparent bond lengths, bond angles,
      and structural distortion with respect to the temperature reveal that geometric
      features associated with the structural distortion cause the anisotropic NZTE
      along c-direction. The preliminary magnetic studies suggest all the compounds are
      paramagnetic at room temperature except LaAgGa3. Electrical resistivity study
      reveals that compounds from this series are metallic in nature.

PMID- 30281285
TI  - Reduction of Cisplatin-Induced Ototoxicity without Compromising Its Antitumor
      Activity.
AB  - Cisplatin is a major chemotherapeutic that continues to have a significant impact
      in the treatment of more than 50% of all cancers. Since its Food and Drug
      Administration approval in 1978 for the treatment of advanced ovarian and bladder
      cancer, this chemotherapeutic has made significant strides and its application
      has been extended to a large variety of other cancers. However, the vast majority
      of patients who receive cisplatin therapy often suffer from nephrotoxicity,
      neurotoxicity, nausea, and ototoxicity. Numerous methods currently exist for
      overcoming nephrotoxicity- and nausea-related side effects, but there is no clear
      prevention to fight ototoxicity and neurotoxicity. In this work, we examined
      Platin- A, a prodrug of cisplatin and aspirin, using preclinical mouse- and
      guinea pig-based models and demonstrated its efficacy with reduced ototoxicity.
      In addition, in vitro studies documented that when Platin- A is used in
      combination with a clinically relevant dose of radiation, its efficacy can
      further be improved by attacking cellular bioenergetic profiles, producing
      multiple modes of DNA damage, and delaying repair of damaged DNA. These studies
      demonstrated novel properties of the prodrug, Platin- A, highlighting its
      superior efficacy with reduced toxicity.

PMID- 30281286
TI  - Changes in the Local Structure of Nephila clavipes Dragline Silk Model Peptides
      upon Trifluoroacetic Acid, Low pH, Freeze-Drying, and Hydration Treatments
      Studied by 13C Solid-State NMR.
AB  - The conformational analysis of spider dragline silks is difficult because of the
      amorphous character of the silks. In this article, the fractions of several
      conformations were determined for three 47-mer peptides,
      (Glu)4(Ala)6GlyGly12Ala13Gly14GlnGlyGlyTyrGlyGlyLeuGlySerGlnGly25Ala26Gly27
      ArgGlyGlyLeuGlyGlyGlnGly35Ala36Gly37(Ala)6(Glu)4, with three underlined 13C
      labeled blocks using a 13C CP/MAS NMR method. The conformations of the 13C
      labeled sites change significantly depending on the location of the labeled
      blocks when treated with trifluoroacetic acid, low pH, and freeze-drying. The
      conformations of Ala36 and Gly37 residues are strongly influenced by the specific
      conformation of the (Ala)6 sequence at the C-terminal side, but those of other
      residues, Ala13 and Gly14, and Ala 26 and Gly27, are basically not influenced by
      the conformations of (Ala)6. Through hydration of the beta-sheet peptide, sharp
      peaks with random coil could be observed depending on the position of the
      residue, and this result could be interpreted via the change in the Ramachandran
      map obtained from the molecular dynamics simulation.

PMID- 30281287
TI  - Highly Selective Palladium-Catalyzed Hydroborylative Carbocyclization of
      Bisallenes to Seven-Membered Rings.
AB  - A highly selective palladium-catalyzed hydroborylative carbocyclization of
      bisallenes to afford seven-membered rings has been established. This ring-closing
      coupling reaction showed good functional group compatibility with high chemo- and
      regioselectivity, as seven-membered ring 3 was the only product obtained. The
      extensive use of different linkers, including nitrogen, oxygen, malononitrile,
      and malonate, showed a broad substrate scope for this approach. A one-pot cascade
      reaction was realized by trapping the primary allylboron compound with an
      aldehyde, affording a diastereomerically pure alcohol and a quaternary carbon
      center by formation of a new C-C bond. A comprehensive mechanistic DFT
      investigation is also presented. The calculations suggest that the reaction
      proceeds via a concerted hydropalladation pathway from a Pd(0)-olefin complex
      rather than via a pathway involving a defined palladium hydride species. The
      reaction was significantly accelerated by the coordination of the pendant olefin,
      as well as the introduction of suitable substituents in the bridge, due to the
      Thorpe-Ingold effect.

PMID- 30281288
TI  - Olefin Metathesis-Based Fluorescent Probes for the Selective Detection of
      Ethylene in Live Cells.
AB  - Ethylene is an important plant hormone that is involved in a variety of
      developmental processes including agriculturally important ripening of certain
      fruits. Owing to its significant roles, a number of approaches have previously
      been developed to detect ethylene via molecular interactions. However, there are
      no current approaches for detection that are selective via a discrete homogeneous
      molecular interaction. Here we report two profluorescent chemodosimeters for the
      selective detection of the plant hormone ethylene. The approach consists of a
      BODIPY fluorophore with a pendant ruthenium recognition element based on a
      Hoveyda-Grubbs second generation catalysts. A marked increase in fluorescence is
      observed upon exposure to ethylene and selectivity is observed for ethylene over
      other alkenes, providing a unique approach toward ethylene detection. Imaging in
      live cells demonstrated that ethylene could be detected from multiple relevant
      sources.

PMID- 30281289
TI  - Terminal Functionalization with a Triptycene Motif That Dramatically Changes the
      Structural and Physical Properties of an Amorphous Polymer.
AB  - A surprising terminal-group effect on the structural and physical properties of
      an amorphous polymer is reported. We recently demonstrated that triptycene
      derivatives with substituents at the 1,8,13-positions show specific self-assembly
      behavior, enabling the formation of a well-defined "2D + 1D" structure based on
      nested hexagonal packing of the triptycenes. Upon terminal functionalization with
      a 1,8-substituted triptycene (1,8-Trip), a liquid polymer, polydimethylsiloxane
      (PDMS, Mn = 18-24 kDa), turned into a highly viscous solid that exhibits
      birefringence at 25  degrees C. Small-angle and wide-angle X-ray scattering
      measurements revealed that the resulting telechelic PDMS assembles into a 2D + 1D
      structure, where layers of PDMS domains, formed between 2D assemblies of the
      triptycene termini, stack into a 1D multilayer structure with a layer spacing of
      18-20 nm. Because of this structuring, the complex viscosity of the telechelic
      PDMS was dramatically enhanced, providing a value 4 orders of magnitude greater
      than that of the original PDMS. Remarkably, the structural and physical
      properties of PDMS were hardly changed upon terminal functionalization with
      another regioisomer of triptycene (1,4-Trip), which differs only in the
      substitution pattern.

PMID- 30281290
TI  - Biomolecular Assemblies: Moving from Observation to Predictive Design.
AB  - Biomolecular assembly is a key driving force in nearly all life processes,
      providing structure, information storage, and communication within cells and at
      the whole organism level. These assembly processes rely on precise interactions
      between functional groups on nucleic acids, proteins, carbohydrates, and small
      molecules, and can be fine-tuned to span a range of time, length, and complexity
      scales. Recognizing the power of these motifs, researchers have sought to emulate
      and engineer biomolecular assemblies in the laboratory, with goals ranging from
      modulating cellular function to the creation of new polymeric materials. In most
      cases, engineering efforts are inspired or informed by understanding the
      structure and properties of naturally occurring assemblies, which has in turn
      fueled the development of predictive models that enable computational design of
      novel assemblies. This Review will focus on selected examples of protein
      assemblies, highlighting the story arc from initial discovery of an assembly,
      through initial engineering attempts, toward the ultimate goal of predictive
      design. The aim of this Review is to highlight areas where significant progress
      has been made, as well as to outline remaining challenges, as solving these
      challenges will be the key that unlocks the full power of biomolecules for
      advances in technology and medicine.

PMID- 30281292
TI  - On Fe-Fe Dumbbells in the Ideal and Real Structures of FeGa3.
AB  - The intermetallic phase FeGa3 belongs to the rare examples of substances with
      transition metals where semiconducting behavior is found. The necessary electron
      count of 17 ve/fu can be formally derived from eight Fe-Ga and one Fe-Fe two
      center-two-electron bond. The situation is reminiscent of the well-known Fe2(CO)9
      scenario, where a direct Fe-Fe two-center-two-electron bond was shown to not be
      present. Fe-Fe interaction in FeGa3 and its substitution variants represents the
      crucial point for explanation of electronic, thermal transport, and optical
      properties of this material. Chemical bonding analysis in position space of FeGa3
      and Fe2(CO)9 on the basis of the topology of the electron localizability
      indicator distribution, QTAIM atoms, two- and three-center delocalization
      indices, domain natural orbitals, IQA analysis, and an evaluation of the Fe-Fe
      dissociation energy yields a complete picture of the partially compensated Fe-Fe
      bond, which is nevertheless strong enough to be of decisive importance.
      Structural reinvestigation of differently synthesized single crystals leads to
      the composition Fe1+ xGa3 (0 <= x <= 0.018), where the additional Fe atoms are
      predicted from DFT/PBE calculations to yield a magnetic moment of about 2 MUB/Fe2
      atom and metallic in-gap states. Accompanying magnetization and ESR measurements
      are consistent with this picture.

PMID- 30281291
TI  - First Dimethyltin-Functionalized Rare-Earth Incorporated Tellurotungstates
      Consisting of {B-alpha-TeW7O28} and {W5O18} Mixed Building Units.
AB  - The facile one-step assembly reaction of Na2WO4.2H2O, Sn(CH3)2Cl2, RE(NO3)3.6H2O
      and K2TeO3 in the presence of dimethylamine hydrochloride as an organic
      solubilizing agent in acidic aqueous solution resulted in a family of dimethyltin
      functionalized rare-earth (RE) incorporated tellurotungstates consisting of {B
      alpha-TeW7O28} and {W5O18} mixed building units [H2N(CH3)2]8Na4H2[RE2(OH)(B-alpha
      TeW7O28)Sn2(CH3)4(W5O18)]2.18H2O [RE = ErIII (1), YbIII (2), HoIII (3), YIII
      (4)]. The most striking structural characteristic of 1-4 is that they all contain
      a novel tetrameric S-shaped [RE2(OH)(B-alpha-TeW7O28)Sn2(CH3)4(W5O18)]214- moiety
      simultaneously including two pentavacant Keggin [B-alpha-TeW7O28]12- and two
      monovacant Lindqvist [W5O18]6- fragments connected by RE and dimethyltin linkers.
      To the best of our knowledge, such dimethyltin-functionalized RE-containing
      tellurotungstates have not been reported before. The visible or NIR solid-state
      emission spectra of 1 and 3 display the characteristic emission bands arising
      from ErIII and HoIII centers. Moreover, various 1-Er/Yb co-doped samples were
      prepared by controlling different mass ratio of Er(NO3)3.6H2O/Yb(NO3).6H2O in the
      range of 0.96:0.04-0.02:0.98. In the visible region, the emission intensity of
      the 1-Er0.40/Yb0.60 co-doped sample reaches the maximum at the mass ratio of
      Er(NO3)3.6H2O/Yb(NO3).6H2O being 0.40:0.60, and this observation is mainly
      derived from the fact that the Yb3+ ions can sensitize the Er3+ ions to enhance
      the emission intensity in the visible region. However, no such phenomenon for the
      1-Er/Yb co-doped samples is seen in the NIR region. Besides, the upconversion
      spectra of the 1-Er/Yb co-doped samples were first observed. In addition, the
      thermal stabilities of 1-4 were also investigated on the crystalline samples and
      the thermal decomposition process of 1 has been deeply studied.

PMID- 30281293
TI  - Effect of Morphology and Concentration on Crossover between Antioxidant and Pro
      oxidant Activity of MgO Nanostructures.
AB  - The toxicity of nanomaterials can sometimes be attributed to photogenerated
      reactive oxygen species (ROS), but these ROS can also be scavenged by
      nanomaterials, yielding opportunities for crossover between the properties. The
      morphology of nanomaterials also influences such features due to defect-induced
      properties. Here we report morphology-induced crossover between pro-oxidant
      activity (ROS generation) and antioxidant activity (ROS scavenging) of MgO. To
      study this process in detail, we prepared three different nanostructures of MgO
      (nanoparticles, nanoplates, and nanorods) and characterized them by HRTEM. These
      three nanostructures effectively generate superoxide anions (O2*-) and hydroxyl
      radicals (*OH) at higher concentrations (>500 MUg/mL) but scavenge O2*- at lower
      concentrations (40 MUg/mL) with successful crossover at 200 MUg/mL. Nanorods of
      MgO generate the highest levels of O2*-, whereas nanoparticles scavenge O2*- to
      the highest extent (60%). Photoluminescence studies reveal that such crossover is
      based on the suppression of F2+ and the evolution of F+, F2+, and F23+ defect
      centers. The evolution of these defect centers reflects the antibacterial
      activity of MgO nanostructures which is initiated at 200 MUg/mL against Gram
      positive S. aureus ATCC 29737 and among different bacterial strains including
      Gram-positive B. subtilis ATCC 6633 and M. luteus ATCC 10240 and Gram-negative E.
      coli ATCC K88 and K. pneumoniae ATCC 10031. Nanoparticles exhibited the highest
      antibacterial (92%) and antibiofilm activity (17%) against B. subtilis ATCC 6633
      in the dark. Interestingly, the nitrogen-centered free radical DPPH is scavenged
      (100%) by nanoplates due to its large surface area (342.2 m2/g) and the presence
      of the F2+ defect state. The concentration-dependent interaction with an
      antioxidant defense system (ascorbic acid (AA)) highlights nanoparticles as
      potent scavengers of O2*- in the dark. Thus, our findings establish guidelines
      for the selection of MgO nanostructures for diverse therapeutic applications.

PMID- 30281294
TI  - Encapsulation of Phosphotungstic Acid into Metal-Organic Frameworks with Tunable
      Window Sizes: Screening of PTA@MOF Catalysts for Efficient Oxidative
      Desulfurization.
AB  - Clean fuels with extremely low sulfur content are highly desirable due to
      environmental concerns. Herein, three water-stable and eco-friendly metal-organic
      frameworks with tunable window diameters, denoted as MOF-808X, have been employed
      as PTA solid supports. An array of PTA@MOF-808X composites were facilely
      synthesized via the encapsulation strategy. With tunable window sizes and
      adjustable PTA loading amounts, the obtained PTA@MOF-808X composites were
      screened for catalytic oxidative desulfurization (ODS) with H2O2 serving as
      oxidant. The experiments found that 42%PTA@MOF-808A had the highest catalytic ODS
      activity and could completely remove dibenzothiophene (DBT) in a model fuel with
      an initial sulfur content of 1000 ppm within 30 min, which falls far below the
      acceptable limits for fuel standards (10 ppm). Further investigations revealed
      that this high catalytic activity could be attributed to the cooperative
      catalysis of metal clusters in the host framework and the guest PTA molecules.
      Moreover, 42%PTA@MOF-808A could be facilely recovered and reused for at least
      five runs without loss of catalytic activity. Having a combination of eco
      sustainability, high stability, high catalytic activity, and good recyclability,
      42%PTA@MOF-808A therefore represents a new benchmark material for catalytic ODS
      and provides a new perspective for ultradeep desulfurization.

PMID- 30281295
TI  - Seeking Redox Activity in a Tetrazinyl Pincer Ligand: Installing Zerovalent Cr
      and Mo.
AB  - Reaction of the readily reduced pincer ligand bis-tetrazinylpyridine, btzp, with
      the zerovalent metal source M(CO)3(MeCN)3 yields M(btzp)2 for M = Cr, Mo. These
      diamagnetic molecules show intrapincer bond lengths consistent with major charge
      transfer from metal to ligand, a result which is further supported by X-ray
      photoelectron spectroscopy. These molecules show up to five reversible outer
      sphere electron transfers by cyclic voltammetry. The electronic structure of
      neutral M(btzp)2 is analyzed by DFT and CASSCF calculations, which reveal the
      degree of back-donation from the metal into pincer pi* orbitals and also subtle
      differences in metal-ligand interaction for Mo vs Cr. Near-IR absorptions
      exhibited by both M(btzp)2 species originate from charge transfer among
      differently reduced tetrazine rings, which thus further support pincer reduction
      in these species.

PMID- 30281296
TI  - Identifying Charge Transfer Mechanisms across Semiconductor Heterostructures via
      Surface Dipole Modulation and Multiscale Modeling.
AB  - The design and fabrication of stable and efficient photoelectrochemical devices
      requires the use of multifunctional structures with complex heterojunctions
      composed of semiconducting, protecting, and catalytic layers. Understanding
      charge transport across such devices is challenging due to the interplay of bulk
      and interfacial properties. In this work, we analyze hole transfer across n
      Si(111)- R|TiO2 photoanodes where - R is a series of mixed aryl/methyl monolayers
      containing an increasing number of methoxy units (mono, di, and tri). In the
      dimethoxy case, triethylene glycol units were also appended to substantially
      enhance the dipolar character of the surface. We find that hole transport is
      limited at the n-Si(111)- R|TiO2 interface and occurs by two processes-
      thermionic emission and/or intraband tunneling-where the interplay between them
      is regulated by the interfacial molecular dipole. This was determined by
      characterizing the photoanode experimentally (X-ray photoelectron spectroscopy,
      voltammetry, impedance) with increasingly thick TiO2 films and complementing the
      characterization with a multiscale computational approach (first-principles
      density functional theory (DFT) and finite-element device modeling). The tested
      theoretical model that successfully distinguished thermionic emission and
      intraband tunneling was then used to predict the effect of solution potential on
      charge transport. This prediction was then experimentally validated using a
      series of nonaqueous redox couples (ferrocence derivatives spanning 800 mV). As a
      result, this work provides a fundamental understanding of charge transport across
      TiO2-protected electrodes, a widely used semiconductor passivation scheme, and
      demonstrates the predictive capability of the combined DFT/device-modeling
      approach.

PMID- 30281297
TI  - Molecular Origins of the Apparent Ideal CO2 Solubilities in Binary Ionic Liquid
      Mixtures.
AB  - Molecular dynamics (MD) simulations were conducted to investigate the variation
      of Henry's constant of CO2 in two binary ionic liquid mixtures. One of the
      mixtures is formed by pairing the cation 1- n-butyl-3-methylimidazolium [C4mim]+
      with chloride Cl- and methylsulfate [MeSO4]-, whereas the other binary ionic
      liquid mixture contains [C4mim]+ in combination with the anions Cl- and
      bis(trifluoromethanesulfonyl)imide [NTf2]-. In order to provide a microscopic
      understanding of the behavior of the Henry's constant with the anion composition,
      MD simulations of ionic liquid mixtures with and without CO2 saturation were
      performed at 353 K and 10 bar. Our calculations indicate that the Henry's
      constant for CO2 follows a highly nonlinear, although expected based on ideal
      solubility, trend with respect to the increasing concentration of Cl- in
      [C4mim]Cl x[NTf2]1- x, whereas the Henry's constant is almost independent of the
      anion composition in the [C4mim]Cl x[MeSO4]1- x system. Structural analyses
      presented in terms of radial, spatial, and angular distribution functions point
      to significant structural reorganization of the anions around cations in the
      [C4mim]Cl x[NTf2]1- x system. Because of the weakly coordinating ability of the
      [NTf2]- anion with the cation, the [NTf2]- anion is displaced from the equatorial
      plane of the imidazolium ring and occupies positions above and below the ring,
      enabling enhanced CO2-[NTf2]- association. The rearrangement also weakens the
      cation pi-pi interactions, resulting in the formation of increased local free
      volume aiding CO2 accommodation. On the contrary, such structural transitions are
      absent in the [C4mim]Cl x[MeSO4]1- x mixture system.

PMID- 30281298
TI  - Linear Bidentate Ligands (L) with Two Terminal Pyridyl N-Donor Groups Forming
      Pt(II)LCl2 Complexes with Rare Eight-Membered Chelate Rings.
AB  - NMR and X-ray diffraction studies were conducted on Pt(II)LCl2 complexes prepared
      with the new N-donor ligands N(SO2R)Me ndpa (R = Me, Tol; n = 2, 4). These
      ligands differ from N(H)dpa (di-2-picolylamine) in having the central N within a
      tertiary sulfonamide group instead of a secondary amine group and having Me
      groups at the 6,6'-positions ( n = 2) or 3,3',5,5'-positions ( n = 4) of the
      pyridyl rings. The N(SO2R)3,3',5,5'-Me4dpa ligands are coordinated in a bidentate
      fashion in Pt( N(SO2R)3,3',5,5'-Me4dpa)Cl2 complexes, forming a rare eight
      membered chelate ring. The sulfonamide N atom did not bind to Pt(II), consistent
      with indications in the literature that tertiary sulfonamides are unlikely to
      anchor two meridionally coordinated five-membered chelate rings in solutions of
      coordinating solvents. The N(SO2R)6,6'-Me2dpa ligands coordinate in a monodentate
      fashion to form the binuclear complexes [ trans-Pt(DMSO)Cl2]2( N(SO2R)6,6'
      Me2dpa). The monodentate instead of bidentate N(SO2R)6,6'-Me2dpa coordination is
      attributed to 6,6'-Me steric bulk. These binuclear complexes are indefinitely
      stable in DMF- d7, but in DMSO- d6 the N(SO2R)6,6'-Me2dpa ligands dissociate
      completely. In DMSO- d6, the bidentate ligands in Pt( N(SO2R)3,3',5,5'-Me4dpa)Cl2
      complexes also dissociate, but incompletely; these complexes provide rare
      examples of association-dissociation equilibria of N,N bidentate ligands in
      Pt(II) chemistry. Like typical cis-PtLCl2 complexes, the Pt( N(SO2R)3,3',5,5'
      Me4dpa)Cl2 complexes undergo monosolvolysis in DMSO- d6 to form the [Pt(
      N(SO2R)3,3',5,5'-Me4dpa)(DMSO- d6)Cl]+ cations. However, unlike typical cis
      PtLCl2 complexes, the Pt( N(SO2R)3,3',5,5'-Me4dpa)Cl2 complexes surprisingly do
      not react readily with the excellent N-donor bioligand guanosine. A comparison of
      the structural features of over 50 known relevant Pt(II) complexes having smaller
      chelate rings with those of the very few relevant Pt(II) complexes having eight
      membered chelate rings indicates that the pyridyl rings in Pt( N(SO2R)3,3',5,5'
      Me4dpa)Cl2 complexes are well positioned to form strong Pt-N bonds. Therefore,
      the dissociation of the bidentate ligand and the poor biomolecule reactivity of
      the Pt( N(SO2R)3,3',5,5'-Me4dpa)Cl2 complexes arise from steric consequences
      imposed by the -CH2-N(SO2R)-CH2- chain in the eight-membered chelate ring.

PMID- 30281299
TI  - The Role of Mixed Amine/Amide Ligation in Nickel Superoxide Dismutase.
AB  - Superoxide dismutases (SODs) utilize a ping-pong mechanism in which a redox
      active metal cycles between oxidized and reduced forms that differ by one
      electron to catalyze the disproportionation of superoxide to dioxygen and
      hydrogen peroxide. Nickel-dependent SOD (NiSOD) is a unique biological solution
      for controlling superoxide levels. This enzyme relies on the use of cysteinate
      ligands to bring the Ni(III/II) redox couple into the range required for
      catalysis (~300 mV vs. NHE). The use of cysteine thiolates, which are not found
      in any other SOD, is a curious choice because of their well-known oxidation by
      peroxide and dioxygen. The NiSOD active site cysteinate ligands are resistant to
      oxidation, and prior studies of synthetic and computational models point to the
      backbone N-donors in the active site (the N-terminal amine and the amide N atom
      of Cys2) as being involved in stabilizing the cysteines to oxidation. To test the
      role of the backbone N-donors, we have constructed a variant of NiSOD wherein an
      alanine residue was added to the N-terminus (Ala0-NiSOD), effectively altering
      the amine ligand to an amide. X-ray absorption, electronic absorption, and
      magnetic circular dichroism (MCD) spectroscopic analyses of as-isolated Ala0
      NiSOD coupled with density functional theory (DFT) geometry optimized models that
      were evaluated on the basis of the spectroscopic data within the framework of DFT
      and time-dependent DFT computations are consistent with a diamagnetic Ni(II) site
      with two cysteinate, one His1 amide, and one Cys2 amidate ligands. The variant
      protein is catalytically inactive, has an altered electronic absorption spectrum
      associated with the nickel site, and is sensitive to oxidation. Mass
      spectrometric analysis of the protein exposed to air shows the presence of a
      mixture of oxidation products, the principal ones being a disulfide, a bis
      sulfenate, and a bis-sulfinate derived from the active site cysteine ligands.
      Details of the electronic structure of the Ni(III) site available from the DFT
      calculations point to subtle changes in the unpaired spin density on the S-donors
      as being responsible for the altered sensitivity of Ala0-NiSOD to O2.

PMID- 30281300
TI  - Time-Dependent Formulation of Resonance Raman Optical Activity Spectroscopy.
AB  - In this work, we extend the theoretical framework recently developed for the
      simulation of resonance Raman (RR) spectra of medium-to-large sized systems to
      its chiral counterpart, namely, resonance Raman optical activity (RROA). The
      theory is based on a time-dependent (TD) formulation, with the transition tensors
      obtained as half-Fourier transforms of the appropriate cross-correlation
      functions. The implementation has been kept as general as possible, supporting
      adiabatic and vertical models for the PES representation, both in Cartesian and
      internal coordinates, with the possible inclusion of Herzberg-Teller (HT)
      effects. Thanks to the integration of this TD-RROA procedure within a general
      purpose quantum-chemistry program, both solvation and leading anharmonicity
      effects can be included in an effective way. The implementation is validated on
      one of the smallest chiral molecule (methyloxirane). Practical applications are
      illustrated with three medium-size organic molecules (naproxen-OCD3, quinidine
      and 2-Br-hexahelicene), whose simulated spectra are compared to the corresponding
      experimental data.

PMID- 30281301
TI  - S-Nitroso-N-acetylcysteine Generates Less Carcinogenic N-Nitrosamines in Meat
      Products than Nitrite.
AB  - Nitrite reacts with secondary amines to form N-nitrosamines (N-NA), which lead to
      gastrointestinal cancers. The aim of this study was to compare nitrite with S
      nitrosocysteine (Cys-SNO) and S-nitroso-N-acetylcysteine (NAC-SNO) with respect
      to N-NA formation, which was evaluated by determining the conversion of N
      methylaniline to N-nitrosomethylaniline. Under neutral and acidic pH conditions,
      N-NA formation rate was nitrite > Cys-SNO > NAC-SNO. In the presence of copper or
      nucleophiles, NAC-SNO generated much less N-NA than Cys-SNO. Nitrite and Cys-SNO
      produced higher amounts of N-NA in the presence of oxygen, whereas NAC-SNO was
      almost oxygen insensitive. In meat in the stomach medium, NAC-SNO produced much
      lower amounts of N-NA than other additives. In heated meat, Cys-SNO and NAC-SNO
      generated the nitrosyl-hemochrome pink pigment, better than nitrite. In
      conclusion, NAC-SNO was much less reactive for N-NA formation than nitrite and
      Cys-SNO in conditions relevant to meat production and stomach digestion.

PMID- 30281302
TI  - Thermal Gradient Approach for the Quasi-harmonic Approximation and Its
      Application to Improved Treatment of Anisotropic Expansion.
AB  - We present a novel approach to efficiently implement thermal expansion in the
      quasi-harmonic approximation (QHA) for both isotropic and more importantly,
      anisotropic expansion. In this approach, we rapidly determine a crystal's
      equilibrium volume and shape at a given temperature by integrating along the
      gradient of expansion from 0 Kelvin up to the desired temperature. We compare our
      approach to previous isotropic methods that rely on a brute-force grid search to
      determine the free energy minimum, which is infeasible to carry out for
      anisotropic expansion, as well as quasi-anisotropic approaches that take into
      account the contributions to anisotropic expansion from the lattice energy. We
      compare these methods for experimentally known polymorphs of piracetam and
      resorcinol and show that both isotropic methods agree to within error up to 300
      K. Using the Gruneisen parameter causes up to 0.04 kcal/mol deviation in the
      Gibbs free energy, but for polymorph free energy differences there is a
      cancellation in error with all isotropic methods within 0.025 kcal/mol at 300 K.
      Anisotropic expansion allows the crystals to relax into lattice geometries 0.01
      0.23 kcal/mol lower in energy at 300 K relative to isotropic expansion. For
      polymorph free energy differences all QHA methods produced results within 0.02
      kcal/mol of each other for resorcinol and 0.12 kcal/mol for piracetam, the two
      molecules tested here, demonstrating a cancellation of error for isotropic
      methods. We also find that with expansion in more than a single volume variable,
      there is a non-negligible rate of failure of the basic approximations of QHA.
      Specifically, while expanding into new harmonic modes as the box vectors are
      increased, the system often falls into alternate, structurally distinct harmonic
      modes unrelated by continuous deformation from the original harmonic mode.

PMID- 30281303
TI  - Bromopyrrole Alkaloid Inhibitors of the Proteasome Isolated from a Dictyonella
      sp. Marine Sponge Collected at the Amazon River Mouth.
AB  - The new pyrrole-imidazole and pyrrole-guanidine alkaloids 4-debromooroidin (1), 4
      debromougibohlin (2), 5-debromougibohlin (3), and 5-bromopalau'amine (4), along
      with the known hymenidin (5) and (+)-monobromoisophakellin (6), have been
      isolated from a Dictyonella sp. marine sponge, collected at the Amazon River
      mouth. The bromine-substitution pattern observed for compounds 1, 2 and 4 is
      unusual among bromopyrrole alkaloids isolated from marine sponges. The 20S
      proteasome inhibitory activities of compounds 1-6 have been recorded, with 5
      bromopalau'amine (4) being the most active in this series.

PMID- 30281304
TI  - Carbide-Supported Au Catalysts for Water-Gas Shift Reactions: A New Territory for
      the Strong Metal-Support Interaction Effect.
AB  - Strong metal-support interaction (SMSI) has been regarded as one of the most
      important concepts in heterogeneous catalysis, which has been almost exclusively
      discussed in metal/oxide catalysts. Here, we show that gold/molybdenum carbide
      (Au/MoC x) catalysts feature highly dispersed Au overlayers, strong interfacial
      charge transfer between metal and support, and excellent activity in the low
      temperature water-gas shift reaction (LT-WGSR), demonstrating the active SMSI
      state. Subsequent oxidation treatment results in strong aggregation of Au
      nanoparticles, weak interfacial electronic interaction, and poor LT-WGSR
      activity. The two interface states can be transformed into each other by
      alternative carbonization and oxidation treatments. This work reveals the active
      SMSI effect in metal/carbide catalysts induced by carbonization, which opens a
      new territory for this important concept.

PMID- 30281305
TI  - Preharvest Application of Elicitors to Monastrell Grapes: Impact on Wine
      Polysaccharide and Oligosaccharide Composition.
AB  - This work studied the effect of preharvest application in Monastrell grapes of
      four different elicitors [methyl jasmonate (MeJ), benzothiadiazole (BTH),
      chitosan from fungi (CHSf), and chitosan from seafood (CHSs)] on wine
      polysaccharide and oligosaccharide fractions. The polysaccharide and
      oligosaccharide fractions were isolated and characterized. Neutral
      monosaccharides were released after hydrolysis of polysaccharides and quantified
      by gas chromatography (GC). Sugar composition of oligosaccharides was determined
      after solvolysis by GC of their per-O-trimethylsilylated methyl glycoside
      derivatives. MeJ, BTH, CHSf, and particularly CHSs decrease the polysaccharide
      content in wine. The oligosaccharide concentration was also reduced after both
      CHS treatments. These results pointed to a lower degradation of the skin cell
      wall from treated grapes. We suggested that the cause would be a reinforcement of
      the skin cell wall as a result of the action of these elicitors. In conclusion,
      the application of any of these four elicitors in the clusters of the vineyard
      affected the complex carbohydrate composition of elaborated wine.

PMID- 30281306
TI  - Temperature-Dependent Kinetics of the Reaction of a Criegee Intermediate with
      Propionaldehyde: A Computational Investigation.
AB  - The temperature-dependent kinetics for the reaction of a Criegee intermediate
      (CH2OO) with propionaldehyde (CH3CH2CHO) was investigated using canonical
      variational transition state theory (CVT) in conjunction with the small curvature
      tunneling (SCT) method and the interpolated single point energy (ISPE) method at
      the CCSD(T)/AUG-cc-pVTZ//B3LYP/6-311G(d,p) level of theory. A rich chemistry was
      depicted by the title reaction, though the contributions of all of the reaction
      pathways were limited to atmospheric pressure conditions. The reaction of CH2OO
      with CH3CH2CHO was identified to proceed via the formation of secondary ozonide
      (SOZ), which then underwent a sequence of unimolecular isomerization and
      decomposition reactions to form a variety of products. The obtained rate
      coefficient for the formation of SOZ at 298 K was determined to be k = 2.44 * 10
      12 cm3 molecule-1 s-1. At low temperature, collisionally stabilized SOZ was found
      to be the more stable product. Contrarily, at high temperature, SOZ degraded to
      HCHO, and CH3CH2COOH was found to be the major product. The complete degradation
      mechanism and thermochemistry for the reaction of CH2OO with CH3CH2CHO along with
      their rate coefficients over the temperature range of 200-1000 K are reported.

PMID- 30281307
TI  - Polarizable Drude Model with s-Type Gaussian or Slater Charge Density for General
      Molecular Mechanics Force Fields.
AB  - Gas-phase electric properties of molecules can be computed routinely using wave
      function methods or density functional theory (DFT). However, these methods
      remain computationally expensive for high-throughput screening of the vast
      chemical space of virtual compounds. Therefore, empirical force fields are a more
      practical choice in many cases, particularly since force field methods allow one
      to routinely predict the physicochemical properties in the condensed phases. This
      work presents Drude polarizable models, to increase the physical realism in
      empirical force fields, where the core particle is treated as a point charge and
      the Drude particle is treated either as a 1 s-Gaussian or a ns-Slater ( n = 1, 2,
      3) charge density. Systematic parametrization to large high-quality quantum
      chemistry data obtained from the open access Alexandria Library (
      https://doi.org/10.5281/zenodo.1004711 ) ensures the transferability of these
      parameters. The dipole moments and isotropic polarizabilities of the isolated
      molecules predicted by the proposed Drude models are in agreement with experiment
      with accuracy similar to DFT calculations at the B3LYP/aug-cc-pVTZ level of
      theory. The results show that the inclusion of explicit polarization into the
      models reduces the root-mean-square deviation with respect to DFT calculations of
      the predicted dipole moments of 152 dimers and clusters by more than 50%.
      Finally, we show that the accuracy of the electrostatic interaction energy of the
      water dimers can be improved systematically by the introduction of polarizable
      smeared charges as a model for charge penetration.

PMID- 30281309
TI  - How the Ligand-Induced Reorganization of Protein Internal Energies Is Coupled to
      Conformational Events.
AB  - Here, we introduce a novel computational method to identify the protein
      substructures most likely to support the functionally oriented structural
      deformations that occur upon ligand-binding. To this aim, we study the modulation
      of protein energetics along the trajectory of a molecular dynamics simulation of
      different proteins in the presence and in the absence of their respective
      ligands, namely, human FGF, human second PDZ from human PTP1E/PTPL1, and the N
      terminal domain of human Hsp90. The method is based on the idea that a subset of
      protein residues (hotspots) may initiate the global response via the disassembly
      and reassembly of interactions, which is reflected in the modulation of the
      overall protein energetics. To identify structural hotspots and dynamic states
      linked to the onset of functionally relevant conformational transitions, we
      define an energy profile to monitor the protein energetics, based on a previously
      introduced approach that highlights the essential nonbonded couplings among all
      residues. The energy profiles are calculated along the trajectory to yield a time
      dependent evolution, and their relative population in the presence and absence of
      the ligand is evaluated by means of a clustering procedure. It is found that
      interconversion between clusters, as well as their population and the density of
      specific energy profiles in the vicinity of structural transitions, provides
      specific information on the impact of the ligand in driving the protein
      conformational response. This analysis also highlights the hotspot residues that
      are most responsive to the presence of the ligand. Importantly, identified
      hotspots are in agreement with experimental evidence in the three considered
      systems. We propose that this approach can be generally used in the prediction of
      "allosteric hotspots" and ligand-induced conformational responses, as well as to
      select conformations more likely to support functional transitions (e.g., in the
      framework of adaptive sampling approaches).

PMID- 30281308
TI  - Synthesis and Cytotoxic and Antiviral Profiling of Pyrrolo- and Furo-Fused 7
      Deazapurine Ribonucleosides.
AB  - Three series of isomeric pyrrolo- and furo-fused 7-deazapurine ribonucleosides
      were synthesized and screened for cytostatic and antiviral activity. The
      synthesis was based on heterocyclizations of hetaryl-azidopyrimidines to form the
      tricyclic heterocyclic bases, followed by glycosylation and final derivatizations
      through cross-coupling reactions or nucleophilic substitutions. The
      pyrrolo[2',3':4,5]pyrrolo[2,3- d]pyrimidine and furo[2',3':4,5]pyrrolo[2,3-
      d]pyrimidine ribonucleosides were found to be potent cytostatics, whereas the
      isomeric pyrrolo[3',2',4,5]pyrrolo[2,3- d]pyrimidine nucleosides were inactive.
      The most active were the methyl, methoxy, and methylsulfanyl derivatives exerting
      submicromolar cytostatic effects and good selectivity toward cancer cells. We
      have shown that the nucleosides are activated by intracellular phosphorylation
      and the nucleotides get incorporated to both RNA and DNA, where they cause DNA
      damage. They represent a new type of promising candidates for preclinical
      development toward antitumor agents.

PMID- 30281310
TI  - Preferred Binding Mechanism of Osh4's Amphipathic Lipid-Packing Sensor Motif,
      Insights from Molecular Dynamics.
AB  - Amphipathic helices are key domains of peripheral membrane proteins, targeting
      specific membranes to enable proper protein function as well as changing the
      local topology and lipid dynamics of the membranes they bind. Here, we use
      extended all-atom molecular dynamics to study, in detail, the binding mechanism
      and conformation of the N-terminus of the lipid-transport protein Osh4 in yeast,
      that is, the amphipathic lipid-packing sensor (ALPS) motif. We identified two
      binding conformations: (i) a vertical one with the N-terminus of the peptide
      embedded into the hydrophobic core and (ii) a horizontal, and energetically
      favored, conformation in which the hydrophobic side chains of ALPS are fully
      embedded into the membrane hydrophobic core. From extensive analysis on 21
      trajectories of 2 MUs each, we describe peptide binding in terms of the
      structural changes that both the peptide and the membrane undergo upon binding as
      well as energetics of this interaction. The membrane models in this study include
      a simple binary lipid mixture, with a neutral and a charged lipid (1,2-dioleoyl-
      sn-glycero-3-phosphocholine-1,2-dioleoyl- sn-glycero-3-phospho-l-serine) and
      complex mixtures with lipid compositions characteristic of two organelles in
      yeast (each with more than six lipid types and an accurate sterol content). Our
      conclusions are in agreement with available literature, showing that the ALPS
      peptide is more likely to bind membrane surfaces with packing defects and higher
      anionic character. In addition, we show that there is an interplay between ALPS
      binding an existing packing defect and creating or enhancing one as the peptide
      binds to the membrane, which was previously suggested in the literature.

PMID- 30281311
TI  - Ring-Polymer Molecular Dynamics with Coarse-Grained Treatment of the Rate
      Coefficients of Chlorine Atom Reactions with Methane, Ethane, and Propane.
AB  - To compute the rate coefficients of the hydrogen abstraction of chlorine plus
      methane (Me), ethane (Et), and propane (Pr), extensive ring-polymer molecular
      dynamics (RPMD) calculations are performed in conjunction with the potential
      energy surface of Cl + Me ( J. Chem. Phys. 2006 , 124 , 124306 ). To treat Cl +
      Et and Cl + Pr, the recently proposed coarse-grained treatment ( J. Chem. Phys.
      2017 , 146 , 024108 ) of RPMD is used. Compared with previous results, good
      agreement can be found. Several probable reasons for the temperature dependence
      feature of the rate coefficients of the heavy-light-heavy reactions are discussed
      through a mass coupling model.

PMID- 30281312
TI  - Spin-optotronic Properties of Organometal Halide Perovskites.
AB  - Spin is an intrinsic quantum mechanical property of fundamental particles
      including the electron. The spin property is intimately related to electronic and
      optical properties of molecules and materials. The combination of spin
      (magnetic), electronic, and optical properties of materials, such as organometal
      halide perovskites (OMHP), has attracted increasing attention, which has led to a
      new field termed spin-optotronics based on all three key properties. This growing
      field has implications in emerging technological applications across disciplines,
      including photonics, electronics, spintronics, quantum computation, and
      information storage. This Perspective provides a brief introduction to this field
      from both experimental and computational aspects, with a focus on the effect of
      spin on charge carrier dynamics in OMHP, a class of materials with novel
      properties and promising applications in a number of fields. For instance, recent
      studies have demonstrated the use of ultrafast laser techniques in probing the
      fundamental charge carrier dynamics in relation to spin properties. Because of
      strong spin-orbit coupling (SOC) and broken inversion symmetry that result in
      Rashba and Dresselhaus effects, OMHP are considered ideal for manipulating spin
      states for spin-optotronics applications. In the meantime, on the basis of first
      principles calculations and effective model Hamiltonians, the Rashba splitting in
      locally polarized domains can result in spin-forbidden recombination with
      significantly slow transition rate due to the mismatch of spin and momentum. We
      summarize the state-of-the-art first-principles methods and their current
      limitations for ultrafast charge and spin dynamics for realistic solid-state
      systems in general. To conclude, we note some promising future research and
      development directions for both experimental and theoretical ultrafast spin
      dynamics studies of OMHP.

PMID- 30281313
TI  - Correction to "Local Fluxionality of Surface-Deposited Cluster Catalysts: The
      Case of Pt7 on Al2O3".

PMID- 30281315
TI  - Band Renormalization of Blue Phosphorus on Au(111).
AB  - Most recently, theoretical calculations predicted the stability of a novel two
      dimensional phosphorus honeycomb lattice named blue phosphorus. Here, we report
      on the growth of blue phosphorus on Au(111) and unravel its structural details
      using diffraction, microscopy and theoretical calculations. Most importantly, by
      utilizing angle-resolved photoemission spectroscopy we identify its momentum
      resolved electronic structure. We find that Au(111) breaks the sublattice
      symmetry of blue phosphorus leading to an orbital-dependent band renormalization
      upon the formation of a (4 * 4) superstructure. Notably, the semiconducting two
      dimensional phosphorus realizes its valence band maximum at 0.9 eV binding
      energy, however, shifted in momentum space due to the substrate-induced band
      renormalization.

PMID- 30281316
TI  - Nanosecond-Laser-Based Charge Transfer Plasmon Engineering of Solution-Assembled
      Nanodimers.
AB  - The ability to re-engineer self-assembled functional structures with nanometer
      accuracy through solution-processing techniques represents a big challenge in
      nanotechnology. Herein we demonstrate that Ag+-soldered nanodimers with a steric
      confinement coating of silica can be harnessed to realize an in-solution
      nanosecond laser reshaping to form interparticle conductive pathway with finely
      controlled conductance. The high structural purity of the nanodimers, the rigid
      silica coating, and the uniform (but still adjustable) sub-1-nm interparticle gap
      together determine the success of the laser reshaping process. This method is
      applicable to DNA-assembled nanodimers, and thus promises DNA-based programming
      toward higher structural complexity. The resulting structures exhibit highly
      tunable charge transfer plasmons at visible and near-infrared frequencies
      dictated by the fluence of the laser pulses. Our work provides an in-solution,
      rapid, and nonperturbative route to realize charge transfer plasmonic coupling
      along prescribed paths defined by self-assembly, conferring great opportunities
      for functional metamaterials in the context of chemical, biological, and
      nanophotonic applications. The ability to continuously control a subnm
      interparticle gap and the nanomeric width of a conductive junction also provides
      a platform to investigate modern plasmonic theories involving quantum and
      nonlocal effects.

PMID- 30281314
TI  - Acetalated Dextran Microparticles for Codelivery of STING and TLR7/8 Agonists.
AB  - Vaccines are the most effective tool for preventing infectious diseases; however,
      subunit vaccines, considered the safest type, suffer from poor immunogenicity and
      require adjuvants to create a strong and sustained immune response. As adjuvants,
      pathogen-associated molecular patterns (PAMPs) offer potent immunostimulatory
      properties and defined mechanisms of action through their cognate pattern
      recognition receptors (PRRs). Their activity can be further enhanced through
      combining two or more PAMPs, particularly those that activate multiple immune
      signaling pathways. However, the cytosolic localization of many PRRs requires
      intracellular delivery of PAMPs for optimal biological activity, which is
      particularly true of the stimulator of interferon genes (STING) PRR. Using
      acetalated dextran (Ace-DEX) microparticles (MPs) encapsulating STING agonist
      3'3'-cyclic GMP-AMP (cGAMP) combined with soluble PAMPS, we screened the effect
      of codelivery of adjuvants using primary mouse bone marrow derived dendritic
      cells (BMDCs). We identified that codelivery of cGAMP MPs and soluble Toll-like
      receptor 7/8 (TLR7/8) agonist resiquimod (R848) elicited the broadest cytokine
      response. cGAMP and R848 were then coencapsulated within Ace-DEX MPs via
      electrospray. Using the model antigen ovalbumin, we observed that Ace-DEX MPs
      coencapsulating cGAMP and R848 (cGAMP/R848 Ace-DEX MPs) induced antigen-specific
      cellular immunity, and a balanced Th1/Th2 humoral response that was greater than
      cGAMP Ace-DEX MPs alone and PAMPs delivered in separate MPs. These data indicate
      that polymeric Ace-DEX MPs loaded with STING and TLR7/8 agonists represent a
      potent cellular and humoral vaccine adjuvant.

PMID- 30281317
TI  - Size-Dependent Catalytic Activity of Oxo-Hydroxo Titanium Sub-Nanoislets Grafted
      on Organically Modified Mesoporous Silica.
AB  - The reaction between titanium alkoxides, [Ti(OR)4], and surface silanol groups is
      widely used to generate grafted oxo-hydroxo titanium species, whose size is
      difficult to control. Partial capping of the surface silanols in the presence of
      the masking pattern of self-repelling tetramethylammonium ions allows us to
      isolate surface silanol islets, on which isolated titanium ions and dimeric oxo
      titanium species can be generated up to 2 Ti/Si mol %. Above this loading, and up
      to ~8 Ti/Si mol %, higher oligomers (trimers, hexamers, octamers, and so on) are
      formed, reaching the size obtained at much lower loadings (<1 Ti/Si mol %) on a
      nonmodified silica surface. The downsizing effect produced on our organically
      modified surface is monitored from the blue-shift of the charge-transfer band of
      the Ti(IV) ions, measured by reflectance UV-visible spectroscopy. It is also
      mirrored by a higher catalytic activity in cyclohexene epoxidation, revealing
      that it is not only the isolated Ti species that are active but also the
      oligomers. Regarding the latter, the smaller they are, the more active they are.

PMID- 30281318
TI  - Role of Substrate Stiffness in Tissue Spreading: Wetting Transition and Tissue
      Durotaxis.
AB  - Living tissues undergo wetting transitions: On a surface, they can either form a
      dropletlike cell aggregate or spread as a monolayer of migrating cells. Tissue
      wetting depends not only on the chemical but also on the mechanical properties of
      the substrate. Here, we study the role of substrate stiffness in tissue
      spreading, which we describe by means of an active polar fluid model. Taking into
      account that cells exert larger active traction forces on stiffer substrates, we
      predict a tissue wetting transition at a critical substrate stiffness that
      decreases with tissue size. On substrates with a stiffness gradient, we find that
      the tissue spreads faster on the stiffer side. Furthermore, we show that the
      tissue can wet the substrate on the stiffer side while dewetting from the softer
      side. We also show that, by means of viscous forces transmitted across the
      tissue, the stiffer-side interface can transiently drag the softer-side interface
      toward increasing stiffness, against its spreading tendency. These two effects
      result in directed tissue migration up the stiffness gradient. This phenomenon
      tissue durotaxis-can thus emerge both from dewetting on the soft side and from
      hydrodynamic interactions between the tissue interfaces. Overall, our work
      unveils mechanisms whereby substrate stiffness impacts the collective migration
      and the active wetting properties of living tissues, which are relevant in
      development, regeneration, and cancer.

PMID- 30281319
TI  - Recommended Reading from Rush University Medical Center Fellows.

PMID- 30281321
TI  - Tracheal Submucosal Lymphovenous Malformation.

PMID- 30281320
TI  - Bivalirudin versus heparin monotherapy in non-ST-segment elevation myocardial
      infarction.
AB  - BACKGROUND: The optimal anti-coagulation strategy for patients with non-ST
      elevation myocardial infarction treated with percutaneous coronary intervention
      is unclear in contemporary clinical practice of radial access and potent P2Y12
      inhibitors. The aim of this study was to investigate whether bivalirudin was
      superior to heparin monotherapy in patients with non-ST-elevation myocardial
      infarction without routine glycoprotein IIb/IIIa inhibitor use. METHODS: In a
      large pre-specified subgroup of the multicentre, prospective, randomised,
      registry-based, open-label clinical VALIDATE-SWEDEHEART trial we randomised
      patients with non-ST-elevation myocardial infarction undergoing percutaneous
      coronary intervention, treated with ticagrelor or prasugrel, to bivalirudin or
      heparin monotherapy with no planned use of glycoprotein IIb/IIIa inhibitors
      during percutaneous coronary intervention. The primary endpoint was the rate of a
      composite of all-cause death, myocardial infarction or major bleeding within 180
      days. RESULTS: A total of 3001 patients with non-ST-elevation myocardial
      infarction, were enrolled. The primary endpoint occurred in 12.1% (182 of 1503)
      and 12.5% (187 of 1498) of patients in the bivalirudin and heparin groups,
      respectively (hazard ratio of bivalirudin compared to heparin treatment 0.96, 95%
      confidence interval 0.78-1.18, p=0.69). The results were consistent in all major
      subgroups. All-cause death occurred in 2.0% versus 1.7% (hazard ratio 1.15, 0.68
      1.94, p=0.61), myocardial infarction in 2.3% versus 2.5% (hazard ratio 0.91, 0.58
      1.45, p=0.70), major bleeding in 8.9% versus 9.1% (hazard ratio 0.97, 0.77-1.24,
      p=0.82) and definite stent thrombosis in 0.3% versus 0.2% (hazard ratio 1.33,
      0.30-5.93, p=0.82). CONCLUSION: Bivalirudin as compared to heparin during
      percutaneous coronary intervention for non-ST-elevation myocardial infarction did
      not reduce the composite of all-cause death, myocardial infarction or major
      bleeding in non-ST-elevation myocardial infarction patients receiving current
      recommended treatments with modern P2Y12-inhibitors and predominantly radial
      access.

PMID- 30281322
TI  - USP10 promotes proliferation and migration and inhibits apoptosis of endometrial
      stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway.
AB  - Endometriosis has been initially described as endometrial-like tissue outside of
      the uterine cavity. Mitogen-activated protein kinase/ERK kinase
      (MEK)/extracellular-signal-regulated kinase (ERK) signaling pathway playing an
      important role in the regulation of cell proliferation, apoptosis and migration
      has been found to be activated in endometriosis. However, the regulation of
      MEK/ERK signaling pathway in endometriosis has not been fully understood. In this
      study, primary-cultured endometrial stromal cells were collected from patients
      with endometriosis and healthy controls, and the proliferation, apoptosis and
      migration of ectopic endometrial stromal cells transfected with ubiquitin
      specific protease 10 (USP10)-siRNA or pLVX-Puro-USP10 with or without MEK
      inhibitor PD98059 or exogenous signaling stimulation such as epidermal growth
      factor (EGF) were measured by CCK-8, flow cytometry and Transwell, respectively.
      The gene and protein expressions were measured by Real-time PCR or western blot.
      USP10 overexpression promoted ectopic endometrial stromal cell migration and
      proliferation, suppressed cell apoptosis, and activated MEK/ERK signaling that is
      a critical downstream target of the serine/threonine protein kinase Raf-1, which
      was significantly blocked by PD98059. USP10 silencing demonstrated the inverse
      effects, and these effects induced by USP10 silencing were significantly blocked
      by EGF. USP10 overexpression promoted Raf-1 protein expression, but not the mRNA
      expression, through deubiquitination. In conclusion, these results suggest that
      USP10 promotes proliferation and migration and inhibits apoptosis of endometrial
      stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway.

PMID- 30281323
TI  - Mammalian skeletal muscle does not express functional voltage-gated H+ channels.
AB  - High metabolic activity and existence of a large transmembrane inward
      electrochemical gradient for H+ at rest promote intracellular acidification of
      skeletal muscle. Exchangers and cotransports efficiently contend against
      accumulation of intracellular H+ and associated deleterious effects on muscle
      functions. Voltage-gated H+ channels have also been found to represent another H+
      extrusion pathway in cultured muscle cells. Up to now, the skeletal muscle cell
      was therefore the unique vertebrate excitable cell in which voltage-gated H+
      currents have been described. In this study, we show that, unlike cultured cells,
      single mouse muscle fibers do not generate H+ currents in response to
      depolarization. In contrast, expression of human voltage-gated H+ channels in
      mouse muscle gives rise to robust outward voltage-gated H+ currents. This result
      excludes that inappropriate experimental conditions may have failed to reveal
      voltage-gated H+ currents in control muscle. This work therefore demonstrates
      that fully differentiated mammalian muscle fibers do not express functional
      voltage-gated H+ channels and consequently can be no more considered as the only
      vertebrate excitable cells exhibiting voltage-gated H+ currents.

PMID- 30281325
TI  - Macrophage Polarization in Sarcoidosis: An Unexpected Accomplice?

PMID- 30281324
TI  - Elastase Exocytosis by Airway Neutrophils Associates with Early Lung Damage in
      Cystic Fibrosis Children.
AB  - RATIONALE: Neutrophils are recruited to the airways of individuals with cystic
      fibrosis (CF).In adolescents and adults with CF, airway neutrophils actively
      exocytose the primary granule protease elastase (NE), whose extracellular
      activity correlates with lung damage. During childhood, free extracellular NE
      activity is measurable only in a subset of patients, and the exocytic function of
      airway neutrophils is unknown. OBJECTIVE: We sought to measure NE exocytosis by
      airway neutrophils in relation to free extracellular NE activity and lung damage
      in CF children. METHODS: We measured lung damage using chest computed tomography
      (CT) coupled with the PRAGMA-CF scoring system. Concomitantly, we phenotyped
      blood and bronchoalveolar lavage fluid (BALF) leukocytes by flow and image
      cytometry, and measured free extracellular NE activity using spectrophotometric
      and Forster resonance energy transfer (FRET) assays. Children with airway
      inflammation linked to aerodigestive disorder were enrolled as controls.
      MEASUREMENTS AND MAIN RESULTS: CF but not disease control children harbored BALF
      neutrophils with high exocytosis of primary granules, prior to the detection of
      bronchiectasis. This measure of NE exocytosis correlated with lung damage
      (Rho=0.55, p=0.0008), while the molecular measure of free extracellular NE
      activity did not. This discrepancy may be due to the inhibition of extracellular
      NE by BALF antiproteases and its binding to leukocytes. CONCLUSIONS: NE
      exocytosis by airway neutrophils occurs in all CF children, and its cellular
      measure correlates with early lung damage. These findings implicate live airway
      neutrophils in early CF pathogenesis, which should instruct biomarker development
      and anti-inflammatory therapy in CF children.

PMID- 30281326
TI  - Activation of u-opioid receptors in the rostral ventrolateral medulla blocks the
      sympathetic counter-regulatory response to glucoprivation.
AB  - Activation of neurons in the rostral ventrolateral medulla (RVLM) following
      glucoprivation initiates sympathoadrenal activation, adrenaline release, and
      increased glucose production. Here, we aimed to determine the role of RVLM u
      opioid receptors in the counter-regulatory response to systemic glucoprivation.
      Experiments were performed in sodium pentobarbital anaesthetised male Sprague
      Dawley rats (n=30). Bilateral activation of RVLM u-opioid receptors with DAMGO
      (8mM, 50nl) depressed adrenal sympathetic nerve activity (ASNA), for ~60 minutes
      (n=6; Delta 49.9+/-5.8%, P<0.05). The counter-regulatory response to
      glucoprivation (measured by adrenal sympathetic efferent nerve activity) induced
      by 2-deoxyglucose (2-DG) (n=6; Delta63.6+/-16.5%, P<0.05) was completely blocked
      60 minutes after DAMGO microinjections (n=6; Delta-10.2+/-3.5%, P<0.05).
      Furthermore, DAMGO pre-treatment attenuated the increase in blood glucose levels
      following 2-DG infusion (n=6; 6.1+/-0.7mmol/L vs baseline 5.2+/-0.3mmol/L,
      P>0.05) compared to 2-DG alone (n=6; 7.6+/-0.4mmol/L vs baseline 6.0+/-0.4mmol/L,
      P<0.05). Thus, activation of RVLM u-opioid receptors attenuated the neural
      efferent response to glucoprivation, and reduced glucose production.

PMID- 30281327
TI  - Effect of anatomical change on dose distribution during radiotherapy for
      maxillary sinus carcinoma: passive scattering proton therapy versus volumetric
      modulated arc therapy.
AB  - OBJECTIVE:: Maxillary sinus carcinomas are anatomically situated next to many
      organs at risk (OARs), and anatomical change is often observed during
      radiotherapy. We analyzed the effect of anatomical change on dose distribution of
      passive scattering proton therapy (PSPT) and volumetric-modulated arc therapy
      (VMAT) for 20 patients. METHODS:: The first plans were generated based on the
      first CT images. The second CT images were acquired after 3 weeks, and the second
      plans were generated by copying the first plans to the second CT images. The
      effect of anatomical change was estimated by comparing both plans. RESULTS::
      Target volume change was observed in all cases, however, the influence on dose
      coverage of clinical target volume tended to be small. Alternatively, the doses
      to almost all OARs were increased. In particular, the increase in the dose to
      brainstem (p < 0.001) and optic chiasm (p < 0.001) was significantly higher in
      the second PSPT plan than in the first PSPT plan. Although PSPT is sensitive to
      anatomical change, the dose to OARs remained significantly lower in PSPT plans
      than that in VMAT plans. CONCLUSION:: PSPT was confirmed to be more effective
      than VMAT even the effect of anatomical change was taken into account. Therefore,
      it is expected that the contralateral vision can be preserved reliably while
      optimal target coverage is provided. ADVANCES IN KNOWLEDGE:: PSPT allowed
      significant sparing of OARs even in the result of the second plans affected by
      the anatomical change. PSPT offers benefits over VMAT in reducing dose to several
      OARs.

PMID- 30281328
TI  - Dusting Off Interleukin-9 as a New Therapeutic Target for Pulmonary Fibrosis.

PMID- 30281329
TI  - Feasibility of deriving a novel imaging biomarker based on patient-specific lung
      elasticity for characterizing the degree of COPD in lung SBRT patients.
AB  - OBJECTIVE:: Lung tissue elasticity is an effective spatial representation for
      Chronic Obstructive Pulmonary Disease phenotypes and pathophysiology. We
      investigated a novel imaging biomarker based on the voxel-by-voxel distribution
      of lung tissue elasticity. Our approach combines imaging and biomechanical
      modeling to characterize tissue elasticity. METHODS:: We acquired 4DCT images for
      13 lung cancer patients with known COPD diagnoses based on GOLD 2017 criteria.
      Deformation vector fields (DVFs) from the deformable registration of end
      inhalation and end-exhalation breathing phases were taken to be the ground-truth.
      A linear elastic biomechanical model was assembled from end-exhalation datasets
      with a density-guided initial elasticity distribution. The elasticity estimation
      was formulated as an iterative process, where the elasticity was optimized based
      on its ability to reconstruct the ground-truth. An imaging biomarker (denoted YM1
      3) derived from the optimized elasticity distribution, was compared with the
      current gold standard, RA950 using confusion matrix and area under the receiver
      operating characteristic (AUROC) curve analysis. RESULTS:: The estimated
      elasticity had 90 % accuracy when representing the ground-truth DVFs. The YM1-3
      biomarker had higher diagnostic accuracy (86% vs 71 %), higher sensitivity (0.875
      vs 0.5), and a higher AUROC curve (0.917 vs 0.875) as compared to RA950. Along
      with acting as an effective spatial indicator of lung pathophysiology, the YM1-3
      biomarker also proved to be a better indicator for diagnostic purposes than
      RA950. CONCLUSIONS:: Overall, the results suggest that, as a biomarker, lung
      tissue elasticity will lead to new end points for clinical trials and new
      targeted treatment for COPD subgroups. ADVANCES IN KNOWLEDGE:: The derivation of
      elasticity information directly from 4DCT imaging data is a novel method for
      performing lung elastography. The work demonstrates the need for a mechanics
      based biomarker for representing lung pathophysiology.

PMID- 30281330
TI  - The potential impact of ultrathin filter design on dosimetry and relative
      biological effectiveness in modern image-guided small animal irradiators.
AB  - OBJECTIVE:: Modern image-guided small animal irradiators like the Xstrahl Small
      Animal Radiation Research Platform (SARRP) are designed with ultrathin 0.15 mm Cu
      filters, which compared with more heavily filtrated traditional cabinet-style
      biological irradiators, produce X-ray spectra weighted toward lower energies,
      impacting the dosimetric properties and the relative biological effectiveness
      (RBE). This study quantifies the effect of ultrathin filter design on relative
      depth dose profiles, absolute dose output, and RBE using Monte Carlo techniques.
      METHODS:: The percent depth-dose and absolute dose output are calculated using
      kVDoseCalc and EGSnrc, respectively, while a tally based on the induction of
      double-strand breaks as a function of electron spectra invoked in PENELOPE is
      used to estimate the RBE. RESULTS:: The RBE increases by >2.4% in the ultrathin
      filter design compared to a traditional irradiator. Furthermore, minute
      variations in filter thickness have notable effects on the dosimetric properties
      of the X-ray beam, increasing the percent depth dose (at 2 cm in water) by +
      0.4%/0.01 mm Cu and decreasing absolute dose (at 2 cm depth in water) by 
      1.8%/0.01 mm Cu for the SARRP. CONCLUSIONS:: These results show that modern image
      guided irradiators are quite sensitive to small manufacturing variations in
      filter thickness, and show a small change in RBE compared to traditional X-ray
      irradiators. ADVANCES IN KNOWLEDGE:: We quantify the consequences of ultrathin
      filter design in modern image-guided biological irradiators on relative and
      absolute dose, and RBE. Our results show these to be small, but not
      insignificant, suggesting laboratories transitioning between irradiators should
      carefully design their radiobiological experiments.

PMID- 30281331
TI  - Adverse effects and radiological manifestations of new immunotherapy agents.
AB  - Immunotherapy has had increasing use in Medical Oncology for a diverse range of
      primary malignancies. There are various types of immunotherapy which are grouped
      based on mechanism of action. In recent decades, the immune checkpoint inhibitors
      (ICI) immunotherapies have been at the forefront of Medical Oncology, sparked by
      very encouraging results. Some patients with metastatic cancer who were
      previously deemed palliative were seeing durable response rates and significant
      increased survival with ICIs. The mechanism of action of ICIs vary wildly
      compared to the conventional, cytotoxic chemotherapy, upon which traditional
      radiology response criteria were based and validated upon. Novel responses such
      as pseudo progression, disease response in the context of new metastases and
      prolonged stable disease were observed and correlated with improved patient
      survival with ICI. New radiology response criteria were proposed to better
      capture disease response to ICI; however, the criteria have been applied
      heterogeneously and there is continued work in this sector. In addition to the
      novel responses, ICIs have been linked to numerous, diverse immune-related
      adverse events (irAE) affecting multiple systems. A large majority of these are
      mild, but some irAEs are life threatening. Only some of the irAEs have
      radiological manifestations. It is important that the reporting radiologist
      recognises potential irAE so clinical teams can be alerted, ICI treatment paused
      or cessated and steroid treatment initiated. This review will discuss the
      evolution of the radiology response criteria in ICI and the varied radiological
      appearances of irAE.

PMID- 30281332
TI  - TREM-1 Attenuates RIPK3 Mediated Necroptosis in Hyperoxia Induced Lung Injury in
      Neonatal Mice.
AB  - Hyperoxia-induced injury to the developing lung, impaired alveolarization and
      dysregulated vascularization are critical factors in the pathogenesis of
      bronchopulmonary dysplasia (BPD); however, mechanisms for hyperoxia-induced
      development of BPD are not fully known. Here we show that the triggering receptor
      expressed on myeloid cells 1 (TREM-1) is upregulated in hyperoxia-exposed
      neonatal mice lungs as well as in tracheal aspirates (TA) and lungs of human
      neonates with respiratory distress syndrome (RDS) and BPD as an adaptive response
      to survival in hyperoxia. Inhibition of TREM-1 function using siRNA approach or
      deletion of TREM-1 gene in mice showed enhanced lung inflammation, alveolar
      damage and mortality of hyperoxia-exposed neonatal mice. The treatment of
      hyperoxia-exposed neonatal mice with agonistic TREM-1 antibody decreased lung
      inflammation, improved alveolarization and was associated with diminished
      necroptosis regulating protein receptor-interacting protein kinase 3 (RIPK3).
      Mechanistically, we show that TREM-1 activation alleviates lung inflammation and
      improves alveolarization through down-regulating RIPK3 mediated necroptosis and
      nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3
      (NLRP3)-inflammasome activation in hyperoxia-exposed neonatal mice. These data
      show that activating TREM-1, enhancing angiopoietin 1 signaling or blocking RIPK3
      mediated necroptosis pathway may act as new therapeutic interventions to control
      adverse effects of hyperoxia on the development of BPD.

PMID- 30281333
TI  - Ski Boots Do Not Impair Standing Balance by Restricting Ankle-Joint Mobility.
AB  - OBJECTIVE: This study was undertaken in order to provide new insight into
      sensorimotor control of posture when wearing high-shaft (HS) boots as ski boots.
      BACKGROUND: Previous studies into the effects of HS boots on postural control
      have produced controversial results. Some studies reported postural control
      impairments with ski boots in bipedal postural tasks due to ankle movement
      restrictions without quantifying the actual restrictive effect of these boots and
      specifying the adaptations of the postural control system. METHOD: Eighteen young
      healthy subjects took part in the experiment. Bilateral postural control was
      assessed on stable and unstable surfaces, while standing barefoot or wearing ski
      boots. Center of pressure (COP) parameters, ankle, knee, and hip joints movements
      were calculated and EMG activity from main postural muscles was recorded.
      RESULTS: Ski boots did not restrict the amplitude of ankle angular movements and
      largely impacted COP parameters and EMG activity on stable ground. In conditions
      of mediolateral instability, COP data illustrated an enhanced postural control in
      the frontal plane when wearing ski boots. CONCLUSIONS: Ski boots do not affect
      bipedal postural balance by restricting the ankle angular motions but induce
      complex adaptations of the postural control system which combine factors of a
      mechanical, motor, and sensorial nature. They impede postural control mainly when
      standing on stable ground without producing similar deleterious effects on
      unstable surfaces. APPLICATION: Our results show that HS boots as ski boots can
      improve lateral balance on unstable surfaces, which can contribute to prevent
      fall risk and ankle sprain.

PMID- 30281334
TI  - Effects of Display Curvature, Presbyopia, and Task Duration on Visual Fatigue,
      Task Performance, and User Satisfaction.
AB  - OBJECTIVE: This study examined the effects of display curvature, presbyopia, and
      task duration on visual fatigue, task performance, and user satisfaction.
      BACKGROUND: Although curved displays have been applied to diverse display
      products, and some studies reported their benefits, it is still unknown whether
      the effects of display curvature are presbyopia-specific. METHOD: Each of 64
      individuals (eight nonpresbyopes and eight presbyopes per display curvature)
      performed four 15-min proofreading tasks at one display curvature radius setting
      (600R, 1140R, 4000R, and flat; mm). Diverse measurements were obtained to assess
      visual fatigue, task performance, and user satisfaction. RESULTS: The mean pupil
      diameter was the largest with 1140R, indicating this curvature radius was
      associated with the least development of visual fatigue; 600R was comparable with
      1140R in terms of pupil diameter. The presbyopic group showed a 28.5% slower
      proofreading speed compared with the nonpresbyopic group, whereas their
      proofreading accuracy was comparable. For both groups, the mean visual fatigue
      increased significantly during the first 15 min of proofreading, as indicated by
      a decrease of 0.11 mm in the mean pupil diameter, an increase of 3.8 in the mean
      bulbar conjunctival redness, and an increase of 9.13 in the mean eye complaint
      questionnaire score. CONCLUSION: The effect of display curvature was not
      presbyopia-specific. Low visual fatigue was observed with 1140R and 600R.
      APPLICATION: Display curvature radii near or in the range of 600R and 1140R and
      frequent breaks are recommended for both presbyopic and nonpresbyopic groups to
      reduce their visual fatigue due to visual display terminal tasks.

PMID- 30281335
TI  - Neutrophils engage the kallikrein-kinin system to open up the endothelial barrier
      in acute inflammation.
AB  - Neutrophil recruitment and plasma exudation are key elements in the immune
      response to injury or infection. Activated neutrophils stimulate opening of the
      endothelial barrier; however, the underlying mechanisms have remained largely
      unknown. In this study, we identified a pivotal role of the proinflammatory
      kallikrein-kinin system and consequent formation of bradykinin in neutrophil
      evoked vascular leak. In mouse and hamster models of acute inflammation,
      inhibitors of bradykinin generation, and signaling markedly reduced plasma
      exudation in response to chemoattractant activation of neutrophils. The
      neutrophil-driven leak was likewise suppressed in mice deficient in either the
      bradykinin B2 receptor or factor XII (initiator of the kallikrein-kinin system).
      In human endothelial cell monolayers, material secreted from activated
      neutrophils induced cytoskeletal rearrangement, leading to paracellular gap
      formation in a bradykinin-dependent manner. As a mechanistic basis, we found that
      a neutrophil-derived heparin-binding protein (HBP/azurocidin) displaced the
      bradykinin precursor high-molecular-weight kininogen from endothelial cells,
      thereby enabling proteolytic processing of kininogen into bradykinin by
      neutrophil and plasma proteases. These data provide novel insight into the
      signaling pathway by which neutrophils open up the endothelial barrier and
      identify the kallikrein-kinin system as a target for therapeutic interventions in
      acute inflammatory reactions.-Kenne, E., Rasmuson, J., Renne, T., Vieira, M. L.,
      Muller-Esterl, W., Herwald, H., Lindbom, L. Neutrophils engage the kallikrein
      kinin system to open up the endothelial barrier in acute inflammation.

PMID- 30281337
TI  - "There is Nothing New Except What Has Been Forgotten": The Story of Mechanical
      Ventilation During Extracorporeal Support.

PMID- 30281336
TI  - Gestational Diabetes Prevalence at Moderate and High Altitude.
AB  - : Euser, Anna G., Andrew Hammes, Jared T. Ahrendsen, Barbara Neistadt, David A.
      Weitzenkamp, Javier Gutierrez, Peppi Koivunen, Colleen G. Julian, and Lorna G.
      Moore. Gestational diabetes prevalence at moderate and high altitude. High Alt
      Med Biol. 00:000-000, 2018. BACKGROUND: High-altitude (HA) pregnancies have been
      associated with decreased glucose levels and increased insulin sensitivity versus
      sea level. Our objective was to determine if the prevalence of gestational
      diabetes mellitus (GDM) and the impact of demographic characteristics on GDM
      diagnosis differed at moderate altitude (MA) versus HA. METHODS: Using a
      retrospective cohort design, we compared women living at HA (>8250 ft) and MA
      (4000-7000 ft) during pregnancy. Exclusion criteria were as follows: multiple
      gestation, preexisting diabetes, unavailable GDM results, or relocation from a
      different altitude during pregnancy. GDM diagnosis was determined using Carpenter
      and Coustan criteria. Data were compared by t-test (continuous variables) or chi
      squared tests (categorical variables). Univariate, multivariate, and stepwise
      regression models were used to assess the impact of various factors on GDM
      prevalence. RESULTS: There was no difference in GDM prevalence between altitudes
      in these populations; the relationship between altitude and GDM was
      nonsignificant in all regression analyses. At MA, maternal age, Hispanic
      ethnicity, body mass index (BMI), and gestational age (GA) at testing increased
      GDM incidence in univariate analyses. At HA, maternal age, Hispanic ethnicity,
      and multiparity increased GDM incidence in univariate analyses. CONCLUSION: While
      GDM prevalence did not differ between MA and HA, the impact of maternal
      demographic characteristics on GDM risk varied by altitude group. Higher BMI and
      greater GA at testing increased the incidence of GDM at MA, but not at HA.
      Multiparity had an effect at HA, but not MA. These differences may represent
      subtle differences in glucose metabolism at HA.

PMID- 30281339
TI  - Keeping clinical skills updated.

PMID- 30281340
TI  - Delivering artificial nutrition and hydration safely by feeding pumps.

PMID- 30281342
TI  - An initiative to improve the safeguarding of vulnerable adults.
AB  - Emeritus Professor Alan Glasper, from the University of Southampton, discusses a
      recent guidance report from the Royal College of Nursing, designed to enhance the
      safeguarding of adults at risk of abuse.

PMID- 30281341
TI  - An audit of completion of diaries for rehabilitation in an intensive care unit.
AB  - Intensive care unit (ICU) diaries are increasingly being used in UK hospitals as
      a therapeutic means to address the psychological effects of an ICU stay on
      patients. The National Institute for Health and Care Excellence recommends that
      services are developed to meet the psychological needs of patients following
      critical illness. This article discusses ICU diaries as a service to meet these
      needs. There is a greater demand for evidence-based research to support the
      positive effects of the diaries. Equally, there is a need to highlight the
      negative impact they may have on patients who would not wish to have a diary
      because of the traumatic experience of critical illness. To gain an insight into
      the use of patient diaries, an audit was conducted at one ICU, which found
      compliance with completing them was poor. This article gives an overview of the
      available literature. Recommendations are made to improve the use of ICU diaries
      for clinical practice in the future.

PMID- 30281343
TI  - Identifying and managing acute migraine attacks in adults.
AB  - Paul Bates, Senior Lecturer/Advanced Nurse Practitioner, University of Lincoln,
      pbates@lincoln.ac.uk , explains the most common symptoms, triggers and treatments
      of migraine, and the role of the nurse in patient care.

PMID- 30281344
TI  - Exploring the impact of Brexit.
AB  - Sam Foster, Chief Nurse, Oxford University Hospitals, presents a risk assessment
      of the potential effects of leaving the European Union on nursing and the NHS
      more widely.

PMID- 30281346
TI  - Confronting the black, Asian, minority ethnic nursing degree attainment gap.

PMID- 30281345
TI  - Do we promote advocacy on behalf of our patients?

PMID- 30281347
TI  - Feeding tube securement in critical illness: implications for safety.
AB  - Over 50 % of tape-secured feeding tubes are inadvertently lost. The impact of
      nasal bridle securement on nasogastric (NG) and nasointestinal (NI) tube loss,
      outcome and duration of use was determined from 1 October 2014 (NG) and 1 January
      2010 respectively to 31 December 2017. From this and published data, the
      potential impact of nasal bridles on major complications was determined. Use of
      nasal bridles was independently associated with: an 80% reduction in inadvertent
      NI tube loss (odds ratio (OR): 95% confidence interval (CI): 0.2: 0.12-0.33,
      p<0.0001); increased duration of tube use (2.2 days, 95% CI: 0.7-3.7, p= 0.004);
      and an almost threefold likelihood of tubes being used until no longer needed
      (OR: 2.8, 95%CI: 1.9-4.3, p<0.0001). In a single-room intensive care unit,
      inadvertent tube loss dropped from 53% to 9% and tube redundancy (tube no longer
      required) rose from 20% to 64%. UK-wide bridle securement, by reducing premature
      tube loss and the need for replacement by 40%, could be associated with 1422
      fewer pneumonias or pneumothoraces and 768 fewer deaths.

PMID- 30281348
TI  - Identifying and managing non-complex fractures.
AB  - Helen Chilvers, Senior Lecturer in Nursing, University of Lincoln,
      HChilvers@lincoln.ac.uk , emphasises the importance of understanding the bone
      healing process and describes the care of patients with bony injuries.

PMID- 30281349
TI  - Immunosuppression following organ transplantation. Part 2: complications and
      their management.
AB  - Advances in the care of patients who have had a solid organ transplant has led to
      a growing population of post-transplant patients, who are also living for longer.
      As a result of their longer life expectancy, transplant recipients often face a
      multitude of challenges, including optimising their immunosuppressive regimens
      and managing potential complications. Life-threatening infections, malignancies,
      and organ-specific toxicities are the complications post-transplant patients
      commonly encounter and these complications are often associated with increased
      morbidity and mortality, adverse graft functioning and survival, profound
      impairment in the patient's quality of life, and significant healthcare burden.
      This article, the second of two parts, gives an overview of the issues involved
      in the care of patients who are receiving immunosuppressants. The common
      complications encountered by post-transplant patients are discussed and their
      assessment, management, prevention and treatment explored.

PMID- 30281350
TI  - Highlighting concerns about patient safety in mental health care.
AB  - John Tingle, Associate Professor (Teaching and Scholarship), Nottingham Trent
      University, discusses two recent reports on mental health care, which raise
      important patient safety issues.

PMID- 30281351
TI  - Critical exploration of the new NMC standards of proficiency for registered
      nurses.
AB  - Following its consultation with key stakeholder groups the Nursing and Midwifery
      Council (NMC) has launched Future nurse: standards of proficiency for registered
      nurses ( NMC, 2018a ). These compulsory new standards will be available for use
      in curricula by approved education institutions (AEIs) from the end of January
      2019. In this article, the authors provide their personal perspectives on the
      potential impact of the new standards, particularly focusing on those relating to
      supporting and assessing students from within the practice environment. The new
      roles of practice supervisor, practice assessor and academic assessor are
      explored, making comparisons to the current mentorship role. There is a clear
      need for effective partnerships between AEIs and healthcare organisations as they
      lead on the implementation of the standards. They must think creatively about
      practice placements and provide opportunities for interprofessional supervision,
      so that students can learn about the roles of other disciplines and how to
      collaborate in a multidisciplinary team.

PMID- 30281353
TI  - Understanding Alzheimer's research and the journey towards a cure.

PMID- 30281352
TI  - Developing a new one-stop urology diagnostics service.
AB  - A newly built NHS 'one-stop' urology diagnostics unit has been created to provide
      a genuinely patient-centred experience for all new patients presenting with
      urological symptoms. Patients across the region now receive not only their
      initial specialist consultation, but also all diagnostic investigations and a
      treatment plan during a single visit to the unit. The purpose-built service has
      reduced the patient diagnostic pathway from several visits over many weeks to a
      matter of hours. The unit has facilities for urodynamic studies, ultrasound,
      flexible cystoscopy and trans-rectal ultrasound prostate biopsy in addition to
      full physiological measurement capabilities. Designing a new purpose-built unit
      in the current healthcare climate brought its own challenges as the project
      progressed. Having the right nursing team in place was essential, and this
      article describes the insights afforded in developing the project.

PMID- 30281354
TI  - The testicular cancer nurse specialist: a pivotal role in patient care.

PMID- 30281355
TI  - Adult pressure area care: preventing pressure ulcers.
AB  - Pressure ulcers (PUs) are caused by tissue damage when the blood supply to an
      area of skin is diminished as a result of pressure. Although most pressure ulcers
      are preventable, all patients are at risk. Nurses have a central role in
      prevention and management of pressure areas. They should be able to assess
      patients' risk of developing PUs using evidence-based practice, recognised risk
      assessment tools and by completing a holistic assessment. Nurses must be able to
      identify the risk factors associated with developing PUs and implement
      appropriate measures to deliver harm-free care. Repositioning techniques,
      monitoring and ongoing care strategies are essential for pressure ulcer
      prevention in practice.

PMID- 30281356
TI  - Bladder cancer: overview and management. Part 2: muscle-invasive and metastatic
      bladder cancer.
AB  - This is Part 2 of an article on bladder cancer: an overview of disease and its
      management. Part 1 provided an overview of non-muscle-invasive bladder cancer,
      how the disease presents, is diagnosed and subsequently treated ( Anderson, 2018
      ). Part 2 provides an overview of muscle-invasive and metastatic bladder cancer
      and outlines treatment options currently available to manage the relevant stages
      of the disease. The management of muscle-invasive cancers comprise surgical
      intervention with transurethral resections, cystectomy (removal of the bladder),
      and systemic chemotherapy and radiotherapy (multi-modality treatment). For
      locally advanced and metastatic disease, systemic chemotherapy and radiotherapy
      are offered, but only as a palliative measure. The intent of treatments for
      muscle-invasive disease is curative. For metastatic disease, the intent is
      disease control, extending life, managing symptoms and improving quality-of-life
      outcomes. This article will include the treatments for the relevant stage of
      muscle-invasive and metastatic bladder cancer and highlight the respective risks
      and benefits. The risk factors for bladder cancer, such as smoking, and risks
      associated with relevant treatments are discussed. The role of the
      multidisciplinary team is underlined in the management of bladder cancer,
      specifically the role of the uro-oncology cancer nurse specialist in the
      provision of reassurance and support to patients.

PMID- 30281357
TI  - Bladder cancer: an overview of treatments.

PMID- 30281358
TI  - From staff nurse to nurse consultant Continuing professional development part 6:
      Mentoring and being mentored.
AB  - John Fowler, Educational Consultant, explores CPD for the clinically based nurse,
      looking at the qualities that make a good mentor and the times in a nursing
      career when mentoring is particularly helpful.

PMID- 30281359
TI  - Finding your voice.

PMID- 30281360
TI  - Intermittent self-catheterisation: patient perceptions and experience.

PMID- 30281361
TI  - Epstein-Barr Virus Hepatitis: A Review of Clinicopathologic Features and
      Differential Diagnosis.
AB  - CONTEXT.-: The liver is frequently affected by Epstein-Barr virus (EBV)
      infection, but involvement is commonly subclinical and self-limited. Severe and
      potentially fatal EBV hepatitis has also been occasionally reported in
      immunocompromised patients and, even more rarely, in immunocompetent individuals.
      OBJECTIVE.-: To provide a review of the clinicopathologic findings of EBV
      hepatitis, with a focus on microscopic features and ancillary testing with a
      brief discussion of the differential diagnosis. DATA SOURCES.-: Analysis of the
      pertinent literature (PubMed) and clinical practice experience based on
      institutional materials. CONCLUSIONS.-: Characteristic microscopic findings in
      EBV hepatitis include a diffuse lymphocytic sinusoidal infiltrate in a "string of
      beads" pattern, expansion of portal tracts by a predominantly lymphocytic
      infiltrate, and intact lobular architecture. In situ hybridization of EBV-encoded
      RNA is a helpful ancillary test. Correlation of clinical history, laboratory
      findings, and histopathologic features is essential to distinguish EBV hepatitis
      from autoimmune liver diseases, transplant rejection, lymphomas, and drug-induced
      liver injury.

PMID- 30281362
TI  - A Review of Smoking-Related Interstitial Fibrosis, Respiratory Bronchiolitis, and
      Desquamative Interstitial Pneumonia: Overlapping Histology and Confusing
      Terminology.
AB  - Smoking-related lung diseases traverse a spectrum of clinicopathologic entities,
      with cases often comprising a complex mixture of findings. The complexity of the
      diagnostic process extends beyond the histologic findings to the nomenclature,
      which is murky from a seemingly unending expansion of terms being applied to a
      handful of pathologic changes. Here, we focus our review on smoking-related
      interstitial fibrosis, respiratory bronchiolitis, and desquamative interstitial
      pneumonia, 3 entities that perhaps show the most histologic overlap and suffer
      from competing terminology.

PMID- 30281363
TI  - Approach to the Liver Biopsy in the Patient With Chronic Low-Level
      Aminotransferase Elevations.
AB  - Pathologists sometimes encounter a liver biopsy from an asymptomatic patient with
      unexplained low-level parenchymal liver enzyme elevations. These biopsies often
      have minor histologic changes but are otherwise almost entirely normal. This can
      lead to the quandary of whether or not the features are clinically meaningful and
      how one must formulate a diagnosis from the possibly nonspecific findings of a
      near-normal biopsy. The following discussion focuses on the histologic changes
      that can be seen in these biopsies and the practical issues involved in making a
      diagnosis that provides useful information to the clinician. The literature and
      textbooks addressing the histologic and clinical features of these cases are
      reviewed with an emphasis on the clinical implications of finding nonspecific
      histologic alterations in these patients.

PMID- 30281364
TI  - Succinate Dehydrogenase-Deficient Renal Cell Carcinoma: A Short Review.
AB  - Succinate dehydrogenase (SDH) is a mitochondrial enzyme complex composed of 4
      protein subunits (SDHA, SDHB, SDHC, and SDHD). Germ line mutations of the genes
      encoding these SDH subunits result in hereditary syndromes harboring
      pheochromocytomas/paragangliomas, gastrointestinal stromal tumors, renal cell
      carcinomas, and pituitary adenomas. SDH-deficient renal cell carcinomas are rare,
      with a mean age of 38 to 40 years. Histologically, these tumors show a
      characteristic appearance that includes a solid, nested, or tubular architecture
      with variable cysts. Cells are typically cuboidal, have indistinct cell borders
      and eosinophilic cytoplasm, and show flocculent intracytoplasmic inclusions. Loss
      of immunohistochemical staining for SDHB is the hallmark of these tumors.
      Although most SDH-deficient renal cell carcinomas are clinically indolent, some
      tumors may behave aggressively, particularly those with a high nuclear grade,
      tumor necrosis, or sarcomatoid differentiation. Accurate classification of these
      tumors is important for clinical follow-up, screening, and genetic evaluation of
      the patients and other family members for this hereditary tumor syndrome.

PMID- 30281365
TI  - Dedifferentiated Liposarcoma With Myofibroblastic Differentiation.
AB  - CONTEXT.-: Liposarcoma is divided into myxoid, pleomorphic, well-differentiated,
      and dedifferentiated subtypes. Dedifferentiated liposarcoma displays the greatest
      histomorphologic diversity, including a subset with myofibroblastic
      differentiation that shares similarities with a spectrum of reactive, benign, and
      malignant soft tissue lesions. Misdiagnosis may lead to deleterious consequences,
      as dedifferentiated liposarcoma differs significantly in its prognosis and
      treatment from its mimics. OBJECTIVE.-: To review the clinicopathologic,
      immunohistochemical, and molecular features of the myofibroblastic variant of
      dedifferentiated liposarcoma as well as the key distinguishing features from its
      mimics. DATA SOURCES.-: Review of pertinent literature on major features and
      current understanding of dedifferentiated liposarcoma with myofibroblastic
      differentiation. CONCLUSIONS.-: The myofibroblastic variant of dedifferentiated
      liposarcoma is an uncommon and underrecognized sarcoma with several important
      differential diagnoses, and likely represents the major subset of aggressive
      retroperitoneal tumors that may have been misdiagnosed as desmoid-type
      fibromatosis, inflammatory myofibroblastic tumor, or another type of sarcoma in
      the past.

PMID- 30281366
TI  - Signet Ring Stromal Cell Tumor: A Legitimate (Benign) Mimic of Krukenberg Tumor.
AB  - Signet ring stromal cell tumor is a rare, benign ovarian neoplasm thought to
      arise from ovarian stromal cells. The pathophysiology of these tumors is poorly
      understood. They present in women in a wide age range, often with nonspecific
      symptoms including lower abdominal or pelvic pain. Their morphologic appearance
      raises a critical differential diagnosis of Krukenberg tumor, an aggressive
      malignancy with significant implications for patient management. For this reason,
      it is important for the pathologist to be aware of signet ring stromal cell tumor
      and its differentiating features, including useful histochemical and
      immunohistochemical ancillary tests. These tumors are curable with surgical
      excision, and there have been no recurrences or metastases among reported cases.

PMID- 30281367
TI  - Glandular Tumors of the Urachus and Urinary Bladder: A Practical Overview of a
      Broad Differential Diagnosis.
AB  - Primary glandular tumors of the urachus and urinary bladder are an intriguing
      group of clinically and morphologically diverse neoplasms for which there have
      been recent refinements in diagnostic subclassification and advances in molecular
      pathology. In addition, the urachus and urinary bladder may be secondarily
      involved by tumors with glandular differentiation that demonstrate remarkable
      morphologic, immunophenotypic, and molecular overlap. Thus, surgical pathologists
      need to be aware of the broad differential diagnosis of glandular tumors that
      involve the urachus and urinary bladder and have a practical diagnostic framework
      to evaluate these lesions in routine clinical practice. In this review, we
      summarize the salient clinical, morphologic, immunohistochemical, and molecular
      features of glandular tumors of the urachus and urinary bladder, including
      mucinous cystic tumors of the urachus, noncystic urachal adenocarcinomas,
      urothelial carcinomas with glandular or pseudoglandular features, primary urinary
      bladder adenocarcinomas, and Mullerian-type carcinomas, highlighting the
      strengths and limitations of various diagnostic features and ancillary tests, as
      well as the need for close clinical and radiographic correlation.

PMID- 30281368
TI  - Biphenotypic Sinonasal Sarcoma: A Review and Update.
AB  - CONTEXT.-: Biphenotypic sinonasal sarcoma (BSNS) is a rare, slow-growing soft
      tissue sarcoma of the sinonasal tract, typically presenting with nonspecific
      obstructive nasal symptoms. Although recurrences are common, no metastases have
      been reported, and only 1 patient has died of disease thus far. It
      characteristically demonstrates rearrangements of PAX3 with multiple fusion
      partners, the most common of which is MAML3. OBJECTIVES.-: To highlight the most
      important diagnostic features, including morphologic, immunohistochemical, and
      molecular findings, and to provide comparisons to other entities in the
      differential diagnosis. We also aim to provide a summary of the clinical features
      and outcomes in cases reported to date. DATA SOURCES.-: Recently published
      literature encompassing BSNS and its synonym, low-grade sinonasal sarcoma with
      neural and myogenic differentiation. CONCLUSIONS.-: BSNS is a sinonasal tumor
      that is important to recognize because its biologic behavior differs from most of
      the entities in the differential diagnosis. The diagnosis can typically be
      rendered through a combination of morphology, immunohistochemical stains, and
      ancillary testing for characteristic PAX3 rearrangements.

PMID- 30281369
TI  - Contributions From University of Michigan 2017 New Frontiers in Pathology
      Conference.

PMID- 30281370
TI  - Atypical Ductal Lesions of the Breast: Criteria, Significance, and Laboratory
      Updates.
AB  - CONTEXT.-: Atypical ductal hyperplasia (ADH) is a challenging diagnosis defined
      by cytologic and architectural features that carries an increased risk of
      subsequent carcinoma when diagnosed in isolation. In addition, ADH may
      secondarily involve benign breast lesions, wherein it carries variable clinical
      significance. OBJECTIVES.-: To review the diagnostic criteria and clinical
      significance of ADH in isolation and as it involves benign breast lesions, and to
      review the evolving literature on its molecular signature. DATA SOURCES.-:
      Recently published studies that collectively examine ADH were reviewed.
      CONCLUSIONS.-: Atypical ductal hyperplasia carries an increased risk of
      subsequent carcinoma in isolation and when it involves most benign breast
      lesions. Identifying which cases of ADH will be upgraded to carcinoma has been
      challenging, and new laboratory developments, such as EZH2 overexpression, may
      have a future role.

PMID- 30281371
TI  - Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome (HLRCC): A
      Contemporary Review and Practical Discussion of the Differential Diagnosis for
      HLRCC-Associated Renal Cell Carcinoma.
AB  - CONTEXT.-: Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC) is
      an uncommon disorder with germline-inactivating mutations in the fumarate
      hydratase ( FH) gene. The kidney cancers that develop in patients with HLRCC are
      often unilateral and solitary, with a potentially aggressive clinical course;
      morphologic identification of suspicious cases is of the utmost importance.
      OBJECTIVE.-: To review classic morphologic features of HLRCC-associated renal
      cell carcinoma, the reported morphologic spectrum of these tumors and their
      mimics, and the evidence for use of immunohistochemistry and molecular testing in
      diagnosis of these tumors. DATA SOURCES.-: University of Michigan cases and
      review of pertinent literature about HLRCC and the morphologic spectrum of HLRCC
      associated renal cell carcinoma. CONCLUSIONS.-: Histologic features, such as
      prominent nucleoli with perinucleolar halos and multiple architectural patterns
      within one tumor, are suggestive of HLRCC-associated renal cell carcinoma.
      However, the morphologic spectrum is broad. Appropriate use of FH
      immunohistochemistry and referral to genetic counseling is important for
      detection of this syndrome.

PMID- 30281372
TI  - Sex-Dependent Choroidal Thickness Differences in Healthy Adults: A Study Based on
      Original and Synthesized Data.

PMID- 30281373
TI  - Lenticule Thickness Accuracy and Influence in Predictability and Stability for
      Different Refractive Errors after SMILE in Chinese Myopic Eyes.
AB  - PURPOSE: To evaluate the differences between the estimated and measured lenticule
      thickness and relationships in myopic eyes with different refractive errors after
      small-incision lenticule extraction (SMILE). METHODS: This prospective study
      included a total of 190 eyes (96 patients) with a manifest refraction spherical
      equivalent (MRSE) of -6.16 +/- 1.71 D. The measured lenticule thickness was
      obtained from digital spectral-domain optical coherence tomography image
      analysis. The estimated lenticule thickness was obtained from the software
      program. Comparative statistics and linear regression analyses were performed.
      RESULTS: At 1 month, the estimated lenticule thickness was 113.68 +/- 19.35 um
      and the measured lenticule thickness was 96.9 +/- 17.5 um. The difference between
      the estimated and measured lenticule thickness was 13.63 +/- 9.1 um (p < 0.001)
      thicker. The difference was lower than the mean data in the moderate myopia group
      (9.7 +/- 6.4 um) and larger in the high myopia group (12.3 +/- 8.8 um) and the
      super-high myopia group (17.9 +/- 6.9 um). The discrepancy between the estimated
      and measured lenticule thickness was significantly dependent on the MRSE (p <
      0.001). MRSE only showed significant differences between the three and six-month
      follow-up visit in the super-high myopic group (p = 0.03). CONCLUSION: The
      measured lenticule thickness was thinner than the estimated lenticule thickness
      for SMILE in most eyes. The higher the refraction, the larger the difference
      after SMILE surgery. The mismatch between the estimated and measured thickness
      did not influence the refractive precision and stability of different refractive
      errors.

PMID- 30281374
TI  - Photodynamic therapy on skin melanoma and epidermoid carcinoma cells using
      conjugated 5-aminolevulinic acid with microbial synthesised silver nanoparticles.
AB  - The present research work describes the use of photodynamic therapy (PDT) of drug
      5-aminolevulinic acid (5-ALA) conjugated with microbial synthesised silver
      nanoparticles on skin melanoma (B16F10) and epidermoid carcinoma (A431) cell
      lines. Silver nanoparticles were synthesised using the bacterial strain Bacillus
      licheniformis. The morphology of the nanoparticles was studied using scanning
      electron microscopy (SEM) and elemental analysis of nanoparticles was carried out
      using energy dispersive X-ray spectroscopy (EDX). Fourier-transform infrared
      spectroscopy (FTIR) analysis was performed to assess the functional groups of the
      nanoparticles. Crystalline nature of nanoparticles was assessed using powder X
      ray diffraction (XRD).The cytotoxicity of pure nanoparticles and conjugated
      nanoparticles with 5-ALA using polyethylene glycol (PEG) was assessed on B16F10
      and A431 cell lines and also compared with standard 5-ALA. Production of ROS
      molecules was measured using a 2,7-dichlorofluorescein-diacetate (DCFH-DA) probe.
      The results showed that the 5-ALA-silver nanoparticles conjugate had higher
      cytotoxicity on both the cell lines than the pure ALA and silver nanoparticles.
      Antimicrobial activity of silver nanoparticles was also carried out on food borne
      pathogens and nanoparticles showed comparable antimicrobial activity with
      standard antibiotics.

PMID- 30281375
TI  - Early Detection of Ovarian Dysfunction by Anti-Mullerian Hormone in Adolescent
      and Young Adult-Aged Survivors of Childhood Cancer.
AB  - PURPOSE: Current guidelines recommend screening at-risk childhood cancer
      survivors for ovarian dysfunction using follicle-stimulating hormone (FSH).
      However, FSH identifies diminished ovarian reserve (DOR), a component of ovarian
      dysfunction, in the later stages when fertility preservation is less likely to
      succeed. This analysis evaluates the utility of anti-Mullerian hormone (AMH) for
      the assessment of DOR in adolescent and young adult (AYA)-aged survivors of
      childhood cancer. METHODS: A retrospective chart review of 13- to 21-year-old
      female survivors who received gonadotoxic therapy and were >=2 years off therapy
      was performed. Gonadotoxic treatments were categorized as low, moderate, or high
      risk for future infertility. Patients with AMH below the assay's age-specific
      normal range were identified and stratified by FSH values (normal <=12 mIU/mL).
      Prevalence of low AMH and AMH-FSH subgroups was calculated and risk factors were
      evaluated using logistic regression. RESULTS: AMH was measured in 190 survivors
      who received gonadotoxic treatment; of them, 35.3% had low AMH. Among survivors
      who received <30 Gy cranial radiation and were not on hormone therapy (n = 141),
      18.4% had normal FSH with low AMH. Stratified by future infertility risk, 10.6%
      of low-risk, 38.1% of moderate-risk, and 25.7% of high-risk survivors had normal
      FSH with low AMH (p < 0.01). Within the low-risk group, normal FSH with low AMH
      was significantly associated with older age at diagnosis (p = 0.02). CONCLUSION:
      Nearly 20% of AYA-aged at-risk survivors had low AMH and normal FSH. DOR in these
      patients would have been missed in standard recommended surveillance practices.

PMID- 30281376
TI  - The Effects of Bilateral Priming on Motor Cortex Function in Healthy Adults.
AB  - Bilateral priming is a rehabilitation adjuvant that can improve upper limb motor
      recovery post-stroke. It uses a table-top device to couple the upper limbs
      together such that active flexion and extension of one wrist leads to passive
      movement of the opposite wrist in a mirror symmetric pattern. Bilateral priming
      increases corticomotor excitability (CME) in the primary motor cortex (M1) of the
      passively driven wrist, however the neurophysiological mechanisms underlying this
      increase remain unclear. This study explored these mechanisms by using
      transcranial magnetic stimulation over the right M1 and recording motor evoked
      potentials from the passively driven left extensor carpi radialis of healthy
      adults. Intracortical measures were recorded before and five and 35 minutes after
      a single 15-minute session of priming. 1 ms short-interval intracortical
      inhibition, long-interval intracortical inhibition, late cortical disinhibition
      (LCD) and intracortical facilitation were recorded with a posterior-anterior (PA)
      intracortical current, while CME and short-interval intracortical facilitation
      (SICF) were recorded with both PA and anterior-posterior (AP) currents. CME with
      PA stimulation was also recorded approximately one hour post-priming. PA CME was
      elevated 35 minutes post-priming and remained elevated approximately one hour
      post-priming. LCD decreased and AP SICF increased at both 5 and 35 minutes post
      priming. However, these changes in LCD and AP SICF are unlikely to be the cause
      of the increased PA CME due to the differing timelines of their effects and AP
      and PA currents activating separate interneuron circuits. These results suggest
      bilateral priming does not increase CME through alterations of the intracortical
      circuits investigated here.

PMID- 30281377
TI  - Safety and effectiveness of istradefylline in patients with Parkinson's disease:
      interim analysis of a post-marketing surveillance study in Japan.
AB  - BACKGROUND: Istradefylline is a first-in-class, non-dopaminergic, selective
      adenosine A2A receptor antagonist for the treatment of Parkinson's disease (PD)
      in patients experiencing the wearing-off phenomenon with levodopa (L-DOPA). The
      authors present an interim report from a post-marketing surveillance (PMS)
      evaluating the safety and effectiveness of long-term istradefylline in a real
      world setting. RESEARCH DESIGN AND METHODS: Istradefylline safety was assessed by
      the incidence of adverse events (AE) and adverse drug reactions (ADRs).
      Effectiveness was assessed using the physician's assessment of off-time, off-time
      symptoms and motor dysfunction, unified PD rating scale (UPDRS) Part III score,
      and the physician's global assessment. RESULTS: This analysis evaluated 476
      patients. Istradefylline was generally well tolerated, despite dyskinesia and
      hallucination being the most common ADRs. Reduction in off-time was observed in
      38.2% of patients, off-time symptoms were improved or markedly improved in 44.7%,
      and motor dysfunction was improved or markedly improved in 48.5%. The mean UPDRS
      Part III score decreased from 33.7 to 30.3 at the end of the study. The
      physician's global assessment rated the drug as effective in 61.3% of patients.
      CONCLUSIONS: This PMS provides useful safety and effectiveness data for long-term
      treatment with istradefylline in a real-world setting for patients with PD
      exhibiting the wearing-off phenomenon with L-DOPA.

PMID- 30281378
TI  - Axillary Lymph Node Dissection for Breast Cancer: Efficacy and Complication in
      Developing Countries.
AB  - PURPOSE: Axillary lymph node dissection (ALND) frequently is performed as part of
      the surgical management of breast cancer as a therapeutic and prognostic index,
      but increasingly has been perceived as associated with significant complications.
      Data on efficacy and complications of ALND in Sudan are lacking. The aim of this
      study was to assess the efficacy and complications of ALND in patients with
      breast cancer treated with mastectomy and breast-conserving surgery. METHODS: We
      performed a prospective, hospital-based study in women with invasive breast
      cancer who underwent modified radical mastectomy or breast-conserving surgery
      with ALND between September 2014 and August 2015. The efficacy of ALND was
      defined as retrieval of >= 10 lymph nodes. Complications of ALND were assessed
      objectively and subjectively and defined as either present or absent. RESULTS: Of
      96 patients with breast cancer included in the study, 40 (42%) developed
      postaxillary clearance complications. The median follow-up time was 18 months
      (range, 12 to 24 months). Numbness was reported by 21.9% of patients. Seroma was
      noted in 15.6% and lymphedema in 9.4%. Approximately 9% reported episodes of
      infection or inflammation at the surgical site. None of the studied factors were
      found to affect the incidence of complications significantly. Ten or more lymph
      nodes were retrieved in 81.3% of patients, and nodal metastasis was found in
      62.5%. CONCLUSION: This study shows that the prevalence of undesirable adverse
      effects after ALND is 42%, with paresthesia and seroma being the most prevalent.
      The lymphedema prevalence was low in relation to other evaluated symptoms.

PMID- 30281379
TI  - Cdt1 variants reveal unanticipated aspects of interactions with Cyclin/CDK and
      MCM important for normal genome replication.
AB  - The earliest step in DNA replication is origin licensing which is the DNA loading
      of MCM helicase complexes. The Cdt1 protein is essential for MCM loading during
      G1 phase of the cell cycle, yet the mechanism of Cdt1 function is still
      incompletely understood. We examined a collection of rare Cdt1 variants that
      cause a form of primordial dwarfism (Meier-Gorlin syndrome) plus one hypomorphic
      Drosophila allele to shed light on Cdt1 function. Three hypomorphic variants load
      MCM less efficiently than WT Cdt1, and their lower activity correlates with
      impaired MCM binding. A structural homology model of the human Cdt1-MCM complex
      position the altered Cdt1 residues at two distinct interfaces rather than the
      previously described single MCM interaction domain. Surprisingly, one dwarfism
      allele ( Cdt1-A66T) is more active than WT Cdt1. This hypermorphic variant binds
      both Cyclin A and SCFSkp2 poorly relative to WT Cdt1. Detailed quantitative live
      cell imaging analysis demonstrated no change in stability of this variant
      however. Instead, we propose that Cyclin A/CDK inhibits Cdt1 licensing function
      independently of the creation of the SCFSkp2 phosphodegron. Together, these
      findings identify key Cdt1 interactions required for both efficient origin
      licensing and tight Cdt1 regulation to ensure normal cell proliferation and
      genome stability.

PMID- 30281380
TI  - Anticipatory Postural Adjustments and Spatial Organization of Motor Cortex -
      Evidence of Adaptive Compensations in Healthy Older Adults.
AB  - During anticipated postural perturbations induced by limb movement, the central
      nervous system generates anticipatory postural adjustments (APAs) in the trunk
      and hip musculature to minimize disturbances to equilibrium. Age-related changes
      in functional organization of the nervous system may contribute to changes in
      APAs in older adults. Here we examined if altered APAs of trunk/hip musculature
      in older adults are accompanied by changes in the representation of these muscles
      in motor cortex. 12 healthy older adults, 5 with a history of falls and 7 non
      fallers, were compared to 13 young adults. APAs were assessed during a
      mediolateral arm raise task in standing. Temporal organization of postural
      adjustments was quantified as latency of APAs in the contralateral external
      oblique, lumbar paraspinals and gluteus medius relative to activation of the
      deltoid. Spatial organization was quantified as extent of synergistic
      coactivation between muscles. Volume and location of the muscle representations
      in motor cortex were mapped using transcranial magnetic stimulation. We found
      that older adults demonstrated significantly delayed APAs in the gluteus medius.
      Spatial organization of the muscles in motor cortex differed between groups, with
      the older adults demonstrating more lateral external oblique representation than
      the other two muscles. Separate comparisons of the fallers and non-fallers with
      young adults indicated that non-fallers had the greatest delay in gluteus medius
      APAs and a reduced distance between the representational areas of the lumbar
      paraspinals and gluteus medius. This study indicates that altered spatial
      organization of motor cortex accompanies altered temporal organization of APA
      synergies in older adults.

PMID- 30281381
TI  - The Effectiveness of Intermittent Pneumatic Compression in Therapy of Lymphedema
      of Lower Limbs: Methods of Evaluation and Results.
AB  - BACKGROUND: Evaluation of intermittent pneumatic compression (IPC) in lymphedema
      is classically based on measurements of circumferences and volume of the
      edematous limb. However, although important, it provides only a general
      information without insight into what proceeds under the skin with respect to
      hydromechanical and structural changes. AIM AND METHODS: We present the
      multimodal evaluation of the effectiveness of IPC device in limb edema by
      measuring tissue stiffness, fluid pressure, and flow volume, and
      lymphoscintigraphic and near-infrared fluorescence (NIRF) indocyanine green (ICG)
      lymphography imaging of edema fluid movement, before and after one 45-60 minute
      compression cycle in over 50 patients with lymphedema stage II and III. RESULTS:
      (1) Tissue fluid pressures were lower than those applied by IPC device. (2) The
      higher the applied compression force, the larger the flow volume. (3) Skin
      stiffness (superficial tonometry) decreased mainly in the calf, whereas,
      subcutaneous tissue (deep tonometry) was observed at all limb levels. (4) Skin
      water concentration (dielectric constant) was only insignificantly decreased, but
      subcutaneous extracellular water (bioimpedance Ldex index, fluid movement force
      test) was effectively moved away to limb proximal regions. (5) Imaging tissue
      (edema) fluid flow pathways on lymphoscintigram and real-time flow on NIRF ICG
      video could be observed and were evaluated semiquantitatively. CONCLUSIONS:
      Adjustment of compression parameters to tissue stiffness, fluid accumulation
      volumes, and fluid movement ability (hydraulic conductivity of tissues) at
      various limb levels is indispensable for effective therapy. Redesigning of
      compression devices will be needed to enable applying differentiated compression
      pressures and prolonged timings at various limb levels.

PMID- 30281382
TI  - Validity and Reliability of Three-Dimensional Imaging for Measuring Breast Cancer
      Related Lymphedema in the Upper Limb: A Cross-Sectional Study.
AB  - BACKGROUND: In the past, measurement of upper limb lymphedema was done by water
      displacement (WD), which is frequently cited as the gold standard. For various
      reasons, however, the use of WD is restricted in clinical settings. A more
      precise and easy-to-use method would be favorable. The high precision of three
      dimensional (3D) imaging in comparison to WD has already been reported for
      healthy subjects. The aim of this study is to determine the validity and
      reliability of 3D imaging by comparing it to the WD method in women with
      unilateral upper limb lymphedema. METHODS AND RESULTS: Thirty-nine women with
      unilateral breast cancer-related lymphedema (BCRL) were included, of which 37
      completed two volume measurement techniques (3D and WD) on the BCRL and
      contralateral healthy arm. Slightly larger volumes were measured by the WD method
      in healthy arms (+9.8 mL; p = 0.058) and also in BCRL arms (+18.5 mL; p < 0.001).
      All measurements were performed twice by the same researcher to evaluate
      reliability. There was no significant difference between the two measurements for
      healthy arms (p = 0.323) or BCRL arms (p = 0.807) in 3D imaging. Bland-Altman
      plots showed a high limit of agreement between the single measurements. 3D
      imaging had a high intrarater reliability (Intraclass Correlation Coefficient =
      0.999). CONCLUSION: Results show that 3D imaging is an innovative method for
      measuring upper limb volume in BCRL patients. Even though image processing is
      time consuming, 3D imaging combines high reproducibility with high precision. By
      software automation, this technique could easily be integrated into clinical
      routine. It is for this reason that we would recommend implementing the Vectra 3D
      imaging technique for measurement of BCRL.

PMID- 30281383
TI  - 80 Years Old, and Never Looked Better: Rebranding in 2019.

PMID- 30281384
TI  - Complex Decongestive Therapy in Breast Cancer-Related Lymphedema: Does Obesity
      Affect the Outcome Negatively?
AB  - BACKGROUND: The aim of this prospective clinical study was to compare the long
      term efficacy of complex decongestive therapy (CDT) in obese and nonobese
      patients with breast cancer-related lymphedema (BCRL). MATERIALS AND METHODS: A
      total of 59 patients (29 obese patients group 1, 30 normoweight overweight
      patients group 2) with unilateral BCRL were enrolled. All patients underwent CDT
      that included manual lymphatic drainage, intermittent pneumatic compression pump,
      multilayer compression bandaging, lymphedema exercises, and skin care. The CDT
      was performed for 1 hour a day, 5 days a week for 3 weeks. Patients were assessed
      according to limb volume difference before CDT, after CDT, and after 1 year.
      RESULTS: The initial lymphedema volume of group 1 was 866.34 +/- 389.34 mL and
      that of group 2 was 661.84 +/- 470.6 mL (p = 0.031). The lymphedema severity
      percentage of excess volume (PEV) of group 1 was 33.37 +/- 15.71 and that of
      group 2 was 31.86 +/- 19.63, which was moderate lymphedema. After 15 sessions of
      CDT program, in group 1, lymphedema volume decreased to 771.46 +/- 389.14 mL
      (post-CDT p = 0.013) and in group 2, lymphedema volume decreased to 468.38 +/-
      417.36 mL (post-CDT p < 0.0001), and in group 1, PEV decreased to 28.54 +/- 16.84
      (post-CDT p = 0.002) and that in group 2 decreased to 22.1 +/- 16.87 (post-CDT p
      < 0.0001). After 1 year, group 1 reached the baseline values of the extremity
      volumes, but in group 2, the volumes of extremities could maintain their post-CDT
      values. CONCLUSION: Obesity is a factor that deteriorates the CDT efficacy. Early
      treatment, before developing fat accumulation and fibrosis, must be primary goal
      in the treatment of BCRL.

PMID- 30281385
TI  - Highly Synergistic Effects of Melittin with Conventional Antibiotics Against
      Multidrug-Resistant Isolates of Acinetobacter baumannii and Pseudomonas
      aeruginosa.
AB  - BACKGROUND: Morbidity and mortality due to multidrug-resistant (MDR) bacteria are
      of great concern in burn patients. In this critical condition, synergism between
      antimicrobial peptides and conventional antibiotics would be a promising
      strategy. Accordingly, this study aimed to determine the therapeutic value of
      melittin as a natural peptide by examining its synergistic effect with
      conventional antibiotics against MDR isolates of Acinetobacter baumannii and
      Pseudomonas aeruginosa. MATERIALS AND METHODS: Fifteen clinical isolates for each
      kind of bacteria were collected from burn patients. Antibiotic susceptibility of
      all isolates was evaluated by disk diffusion method. The minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration for melittin,
      colistin, doripenem, doxycycline, and ceftazidime were also examined. Fractional
      inhibitory concentration (FIC) of melittin in combination with the antibiotics
      was determined for six MDR isolates. The cytotoxicity of melittin in combination
      with the antibiotics was examined on a normal human cell line. RESULTS: The
      geometric means of MIC (GMMIC) for melittin and doripenem after combination were
      reduced to 61.5- and 51.5-fold, respectively, against MDR A. baumannii isolates.
      These reductions for melittin-doripenem and melittin-ceftazidime against MDR P.
      aeruginosa isolates were (63.5 and 58)-fold and (16 and 11)-fold, respectively.
      FIC for melittin-doripenem against A. baumannii and FIC for melittin-doripenem
      and melittin-ceftazidime against P. aeruginosa strains were <=0.5. This issue
      caused a decrease of up to 104-, 68-, and 17-fold, respectively, in the
      cytotoxicity of melittin. CONCLUSION: In conclusion, the synergism of melittin at
      its nontoxic dose with doripenem and ceftazidime could be of great therapeutic
      value as a topical drug against burn infections caused by MDR bacteria.

PMID- 30281386
TI  - Organ of Corti vibration within the intact gerbil cochlea measured by volumetric
      optical coherence tomography and vibrometry.
AB  - There is indirect evidence that the mammalian cochlea in the low-frequency apical
      and the more commonly-studied high-frequency basal regions function in
      fundamentally different ways. Here, we directly tested this hypothesis by
      measuring sound-induced vibrations of the organ of Corti (OoC) at three turns of
      the gerbil cochlea using volumetric optical coherence tomography vibrometry
      (VOCTV), an approach that permits non-invasive imaging through the bone. In the
      apical turn, there was little frequency selectivity and the displacement-versus
      frequency curves had low-pass filter characteristics with a corner frequency of
      ~0.5-0.9 kHz. The vibratory magnitudes increased compressively with increasing
      stimulus intensity at all frequencies. In the middle turn, responses were similar
      except for a slight peak in the response at ~2.5 kHz. The gain was ~ 50 dB at the
      peak and 30-40 dB at lower frequencies. In the basal turn, responses were sharply
      tuned and compressively nonlinear, consistent with observations in the
      literature. These data demonstrated that there is a transition of the mechanical
      response of the OoC along the length of the cochlea such that frequency tuning is
      sharper in the base than in the apex. Since the responses are fundamentally
      different, it is not appropriate to simply frequency shift vibratory data
      measured at one cochlear location to predict the cochlear responses at other
      locations. Furthermore, this means that the number of hair cells stimulated by
      sound is larger for low-frequency stimuli and smaller for high-frequency stimuli
      for the same intensity level. Thus, the mechanisms of central processing of
      sounds must vary with frequency.

PMID- 30281388
TI  - Synergies in coordination: a comprehensive overview of neural, computational and
      behavioral approaches.
AB  - At face value, the term 'synergy' provides a unifying concept within a fractured
      field that encompasses complementary neural, computational and behavioral
      approaches. However, the term is not used synonymously by different researchers,
      but has substantially different meanings depending on the research approach. With
      so many operational definitions for the one term, it becomes difficult to use as
      either a descriptive or explanatory concept, yet it remains pervasive and
      apparently indispensable. Here we provide a summary of different approaches that
      invoke 'synergies' in a descriptive or explanatory context, summarizing progress,
      not within the one approach, but across the theoretical landscape. Bernstein's
      framework of flexible hierarchical control may provide a unifying framework here,
      since it can incorporate divergent ideas about synergies. In the current motor
      control literature, 'synergy' may refer to conceptually different processes that
      could potentially operate in parallel, across different levels within the same
      hierarchical control scheme. There is evidence for the concurrent existence of
      synergies with different features, both 'hard-wired' and 'soft-wired', task
      independent and task-dependent. By providing a comprehensive overview of the
      multifaceted ideas about synergies, our goal is to move away from the
      compartmentalization and narrow focus on one level and promote a broader
      perspective on the control and coordination of movement.

PMID- 30281387
TI  - Men's Fear of Mentoring in the #MeToo Era - What's at Stake for Academic
      Medicine?

PMID- 30281389
TI  - New Tools in the Ebola Arsenal.

PMID- 30281390
TI  - Choanoflagellate transfection illuminates their cell biology and the ancestry of
      animal septins.
AB  - As the closest living relatives of animals, choanoflagellates offer unique
      insights into animal origins and core mechanisms underlying animal cell biology.
      However, unlike traditional model organisms, such as yeast, flies and worms,
      choanoflagellates have been refractory to DNA delivery methods for expressing
      foreign genes. Here we report the establishment of a robust method for expressing
      transgenes in the choanoflagellate Salpingoeca rosetta, overcoming barriers that
      have previously hampered DNA delivery and expression. To demonstrate how this
      method accelerates the study of S. rosetta cell biology, we engineered a panel of
      fluorescent protein markers that illuminate key features of choanoflagellate
      cells. We then investigated the localization of choanoflagellate septins, a
      family of GTP-binding cytoskeletal proteins that are hypothesized to regulate
      multicellular rosette development in S. rosetta. Fluorescently tagged septins
      localized to the basal pole of S. rosetta single cells and rosettes in a pattern
      resembling septin localization in animal epithelia. The establishment of
      transfection in S. rosetta and its application to the study of septins represent
      critical advances in the growth of S. rosetta as an experimental model for
      investigating choanoflagellate cell biology, core mechanisms underlying animal
      cell biology, and the origin of animals.

PMID- 30281391
TI  - Application of the fluctuation theorem for non-invasive force measurement in
      living neuronal axons.
AB  - Although its importance is recently widely accepted, force measurement has been
      difficult in living biological systems, mainly due to the lack of the versatile
      non-invasive force measurement methods. The fluctuation theorem, which represents
      the thermodynamic properties of small fluctuating non-equilibrium systems, has
      been applied to the analysis of the thermodynamic properties of motor proteins in
      vitro. Here, we extend it to the axonal transport (displacement) of endosomes.
      The distribution of the displacement fluctuation had three or four distinct peaks
      around multiples of a unit value, which the fluctuation theorem can convert into
      the drag force exerted on the endosomes. The results demonstrated that a single
      cargo vesicle is conveyed by one to three or four units of force production.

PMID- 30281392
TI  - Advancing Freund's and AddaVax Adjuvant Regimens Using CpG Oligodeoxynucleotides.
AB  - Adjuvant can play an important role in vaccine formulation by aiding in the
      development of a robust immune response. In our hybridoma development work, we
      typically use both Freund's and AddaVaxTM adjuvant regimens for mouse
      immunizations. While we have repeatedly shown success with our protocols, we
      continually seek to improve upon the titer and affinity of the serum antibody
      response. To that end, we evaluated the use of CpG oligodeoxynucleotides (CpG
      DNA), a B cell stimulant, in our adjuvant regimens. Mice were immunized using our
      standard Freund's protocol (Adjulite Complete Freund's Adjuvant for the primary
      immunization followed by Adjulite Incomplete Freund's Adjuvant (AIFA) for all
      additional immunizations) or a test protocol using AIFA supplemented with CpG-DNA
      for all immunizations. A second group of mice were immunized with antigen
      emulsified in AddaVax adjuvant alone or AddaVax supplemented with CpG-DNA. Our
      results show a trend toward a higher titer response when CpG-DNA was used with
      either adjuvant. In addition, AIFA+CpG-DNA mice trended toward a higher relative
      affinity versus mice immunized using our standard Freund's methodology.
      Additional antigens will need to be studied to determine whether these
      observations are limited to the proteins (antigens) studied or whether this is a
      generalized response to any immunogen.

PMID- 30281393
TI  - Phage-displayed peptides targeting specific tissues and organs.
AB  - Phage display is a powerful and widely used technique to find novel peptide
      ligands. A massive amount of peptide sequences have been identified for all kinds
      of materials, and peptides that may have targeting capabilities towards specific
      cells and tissues have received special attention in biomedical sciences. As a
      result, it is increasingly harder to follow all the work that has been done,
      which sometimes leads to many promising ligands receiving little attention,
      together with the publication of false positives that have already been found.
      The aim of this review is to provide an updated and comprehensive list of phage
      displayed peptides targeting different tissues and organs. The limitations of the
      technique are carefully analysed and the future perspectives envisaged.

PMID- 30281394
TI  - Depletion of SMC5/6 sensitizes male germ cells to DNA damage.
AB  - The structural maintenance of chromosomes complex, SMC5/6, is thought to be
      essential for DNA repair and chromosome segregation during mitosis and meiosis.
      To determine the requirements of the SMC5/6 complex during mouse spermatogenesis
      we combined a conditional knockout allele for Smc5, with four germ cell specific
      Cre recombinase transgenes, Ddx4-Cre, Stra8-Cre, Spo11-Cre and Hspa2-Cre, to
      mutate Smc5 in spermatogonia, in spermatocytes prior to meiotic entry, during
      early meiotic stages, and during mid-meiotic stages, respectively. Conditional
      mutation of Smc5 resulted in destabilization of the SMC5/6 complex. Despite this,
      we observed only mild defects in spermatogenesis. Mutation of Smc5 mediated by
      Ddx4-Cre and Stra8-Cre resulted in partial loss of pre-leptotene spermatocytes;
      however, spermatogenesis progresses and mice are fertile. Mutation of Smc5 via
      Spo11-Cre or Hspa2-Cre did not result in detectable defects of spermatogenesis.
      Upon exposure to gamma irradiation or etoposide treatment, each conditional Smc5
      mutant demonstrated an increase in enlarged round spermatids with multiple
      acrosomes and supernumerary chromosome content. We propose that the SMC5/6
      complex is not acutely required for pre-meiotic DNA replication and meiotic
      progression during mouse spermatogenesis; however, when germ cells are challenged
      by exogenous DNA damage, the SMC5/6 complex ensures genome integrity, and thus,
      fertility.

PMID- 30281395
TI  - Serotonin regulates the dynamics of cerebellar granule cell activity by
      modulating tonic inhibition.
AB  - Understanding how afferent information is integrated by cortical structures
      requires identifying the factors shaping excitation and inhibition within their
      input layers. The input layer of the cerebellar cortex integrates diverse
      sensorimotor information to enable learned associations that refine the dynamics
      of movement. Specifically, mossy fiber afferents relay sensorimotor input into
      the cerebellum to excite granule cells, whose activity is regulated by inhibitory
      Golgi cells. To test how this integration can be modulated, we have used an acute
      brain slice preparation from young adult rats and found that encoding of mossy
      fiber input in the cerebellar granule cell layer can be regulated by serotonin (5
      HT) via a specific action on Golgi cells. We find that 5-HT depolarizes Golgi
      cells, likely by activating 5-HT2A receptors, but does not directly act on either
      granule cells or mossy fibers. As a result of Golgi cell depolarization, 5-HT
      significantly increases tonic inhibition onto both granule cells and Golgi cells.
      5-HT-mediated Golgi cell depolarization is not sufficient, however, to alter the
      probability or timing of mossy fiber-evoked feed-forward inhibition onto granule
      cells. Together, increased granule cell tonic inhibition paired with normal feed
      forward inhibition acts to reduce granule cell spike probability without altering
      spike timing. These data hence provide a circuit mechanism by which 5-HT can
      reduce granule cell activity without altering temporal representations of mossy
      fiber input. Such changes in network integration could enable flexible, state
      specific suppression of cerebellar sensorimotor input that should not be learned,
      or enable reversal learning for unwanted associations.

PMID- 30281397
TI  - Comparison of rate of tooth movement and pain perception during accelerated tooth
      movement associated with conventional fixed appliances with micro
      osteoperforations - a randomised controlled trial.
AB  - OBJECTIVES: To investigate the influence of micro-osteoperforation (MOP) on rate
      of orthodontic tooth movement and pain perception with fixed appliances. DESIGN:
      2 arm parallel randomized controlled trial with an allocation ratio of 1:1.
      SETTING: The outpatient department of a dental college. PARTICIPANTS: 105
      patients were screened, out of which 60 met the inclusion criteria and consented
      to participate; consisting of 33 females and 27 males requiring en-masse
      retraction following first premolar extractions. METHODS: The experimental group
      consisted of patients bonded with a fixed appliance (Gemini 3M) who received MOP
      distal to canines throughout the period of retraction every 28 days. These were
      compared with a control group treated with identical brackets without MOP and
      were assessed for rate of tooth movement (canine retraction) and pain perception
      using a Visual Analogue Scale (VAS) of 10 mm. RESULTS: Prior to commencement, all
      baseline parameters were matched between the two groups (p>0.05). A statistically
      significant increase in rate of tooth movement in the MOP group (p<0.05).
      CONCLUSION: MOP appears to enhance the rate of tooth movement with no differences
      in pain perception.

PMID- 30281396
TI  - Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the
      Thinking and Living With Cancer Study.
AB  - PURPOSE: To determine treatment and aging-related effects on longitudinal
      cognitive function in older breast cancer survivors. METHODS: Newly diagnosed
      nonmetastatic breast cancer survivors (n = 344) and matched controls without
      cancer (n = 347) 60 years of age and older without dementia or neurologic disease
      were recruited between August 2010 and December 2015. Data collection occurred
      during presystemic treatment/control enrollment and at 12 and 24 months through
      biospecimens; surveys; self-reported Functional Assessment of Cancer Therapy
      Cognitive Function; and neuropsychological tests that measured attention,
      processing speed, and executive function (APE) and learning and memory (LM).
      Linear mixed-effects models tested two-way interactions of treatment group
      (control, chemotherapy with or without hormonal therapy, and hormonal therapy)
      and time and explored three-way interactions of ApoE (epsilon4+ v not) by group
      by time; covariates included baseline age, frailty, race, and cognitive reserve.
      RESULTS: Survivors and controls were 60 to 98 years of age, were well educated,
      and had similar baseline cognitive scores. Treatment was related to longitudinal
      cognition scores, with survivors who received chemotherapy having increasingly
      worse APE scores ( P = .05) and those initiating hormonal therapy having lower LM
      scores at 12 months ( P = .03) than other groups. These group-by-time differences
      varied by ApoE genotype, where only epsilon4+ survivors receiving hormone therapy
      had short-term decreases in adjusted LM scores (three-way interaction P = .03).
      For APE, the three-way interaction was not significant ( P = .14), but scores
      were significantly lower for epsilon4+ survivors exposed to chemotherapy (-0.40;
      95% CI, -0.79 to -0.01) at 24 months than epsilon4+ controls (0.01; 95% CI, 0.16
      to 0.18; P < .05). Increasing age was associated with lower baseline scores on
      all cognitive measures ( P < .001); frailty was associated with baseline APE and
      self-reported decline ( P < .001). CONCLUSION: Breast cancer systemic treatment
      and aging-related phenotypes and genotypes are associated with longitudinal
      decreases in cognitive function scores in older survivors. These data could
      inform treatment decision making and survivorship care planning.

PMID- 30281399
TI  - A Call for Articles: Internet of Things, Artificial Intelligence, Sensors and
      Omics Convergence.

PMID- 30281398
TI  - Effervescent-assisted dispersive liquid-liquid microextraction based on the
      solidification of floating organic droplets for the determination of fungicides
      in vinegar and juice.
AB  - A method of effervescent-assisted dispersive liquid-liquid microextraction based
      on the solidification of a floating organic droplet is reported. This approach
      was used to measure the fungicides myclobutanil, tebuconazole and epoxiconazole
      in vinegar and juice. Acidic vinegar and juice reacted with the carbonate to
      produce effervescence in situ, which then promoted contact of the sample with the
      extraction solvent. The 1-dodecanol extraction solvent helped solidify the
      floating organic droplets and could be fully dispersed by effervescence. The
      extraction solvent, salt, carbonate, and extraction time were optimised. The
      optimal conditions were 200 MUL of 1-dodecanol, 100 mg of sodium chloride, 50 mg
      of sodium bicarbonate, and 30 s of extraction time. The proposed method has good
      linearity between 10 and 1000 ng mL-1. Recoveries were between 70.4% and 103.1%
      in different vinegar and juice samples. This method was successfully used to
      measure fungicides in vinegar and juice. This system is simple, fast and
      environmentally friendly.

PMID- 30281400
TI  - A review of dietary exposure and toxicological information on epoxidised soybean
      oil (ESBO) in food-contact applications.
AB  - Plasticisers have a long history of use in the industrial manufacture and
      processing of polymers for the purpose of increasing the flexibility and strength
      of the material. Approximately, 80-90% of the plasticiser market is devoted to
      the production of PVC, a highly versatile thermoplastic used to produce both
      rigid and flexible articles. Many types of plasticisers, including ortho
      phthalate esters (OPE), can be added to PVC to impart flexibility. Recently,
      alternatives to OPEs, such as epoxy esters and aliphatic adipates, are becoming
      more prevalent for use in PVC-based food-contact articles. Epoxidised soybean oil
      (ESBO) is used as a plasticiser in flexible PVC for many food-contact articles,
      including food packaging and food processing equipment, from which it can
      potentially migrate into food and become a component of an individual's daily
      diet. The purpose of this review is to provide an update on the US dietary
      exposure and toxicological information on ESBO used in PVC-based food-contact
      articles. The cumulative dietary concentration (CDC) and cumulative estimated
      daily intake (CEDI) for ESBO from its use as a plasticiser in PVC-based food
      contact articles (i.e. gaskets for glass jar lids and film wraps) was calculated
      to be 2.6 mg/kg (i.e. ppm) and 0.13 mg/kg bw/d, respectively, for the general
      population. Some regulatory agencies have reported safety levels for ESBO, and
      the most conservative no observed adverse effect level (NOAEL) was identified to
      be 100 mg/kg bw/d (i.e. 2000 ppm) based on a two-year feeding study in rats. The
      current CEDI is well below these levels, supporting the safe use of ESBO in food
      contact applications.

PMID- 30281401
TI  - Elite Handcycling: A Qualitative Analysis of Recumbent Handbike Configuration for
      Optimal Sports Performance.
AB  - Our understanding of handbike configuration is limited, yet it can be a key
      determinant of performance in handcycling. This study explored how fourteen
      handcycling experts (elite handcyclists, coaches, support staff and
      manufacturers) perceived aspects of recumbent handbike configuration to impact
      upon endurance performance via semi-structured interviews. Optimising the
      handbike for comfort, stability and power production were identified as key
      themes. Comfort and stability were identified to be the foundations of endurance
      performance and were primarily influenced by the seat, backrest, headrest and
      their associated padding. Power production was determined by the relationship
      between the athletes' shoulder and abdomen and the trajectories of the handgrips,
      which were determined by the crank axis position, crank arm length and handgrip
      width. Future studies should focus on quantifying the configuration of recumbent
      handbikes before determining the effects that crank arm length, handgrip width
      and crank position have on endurance performance. Practitioner Summary: To gain a
      greater understanding of the impact of handbike configurations on endurance
      performance the perceptions of expert handcyclists were explored qualitatively.
      Optimising the handbike for comfort and stability, primarily via backrest
      padding, and power production, the position of the shoulders relative to
      handgrips and crank axis, were critical.

PMID- 30281402
TI  - Dear Abby: Should I Give Advice or Receive It?
AB  - Typically, individuals struggling with goal achievement seek advice. However, in
      the present investigation ( N = 2,274), struggling individuals were more
      motivated by giving advice than receiving it. In a randomized, controlled, double
      blind field experiment, middle-school students who gave motivational advice to
      younger students spent more time on homework over the following month than
      students who received motivational advice from expert teachers (Experiment 1).
      This phenomenon was replicated across self-regulatory domains: Strugglers who
      gave advice, compared with those who received expert advice, were more motivated
      to save money, control their tempers, lose weight, and seek employment
      (Experiments 2 and 3). Nevertheless, across domains, people erroneously predicted
      the opposite, expecting themselves and others to be less motivated by giving
      advice than receiving it (Experiments 2 and 3). Why are people blind to the
      motivational power of giving? Giving advice motivated givers by raising their
      confidence-a reality that predictors fail to anticipate (Experiment 4).

PMID- 30281403
TI  - Cultivation of scenedesmus sp. using optimized minimal nutrients and flocculants 
      a potential platform for mass cultivation.
AB  - A major constraint in the microalgal technology is the economics involved in
      cultivation and harvesting. This work is focussed on the optimization of
      nutrients for cultivation and harvesting using 'Scenedesmus sp'. Response surface
      methodology (RSM) using 'Face centered central composite design' (FCCD) available
      in Design expert 10.0.4 was used to develop the regression model for optimization
      of nutrients and flocculation conditions. The optimum nutrient conditions were
      500 ppm of urea, 250 ppm of potassium dihydrogen phosphate and 1000 ppm of
      potassium hydrogen carbonate under artificial light conditions and 500 ppm of
      urea and 2000 ppm of potassium hydrogen carbonate under sunlight conditions. The
      optimum conditions were predicted using the model and compared with experimental
      data. The model has an R2 value of 0.9769 and 0.9798 for artificial light and
      sunlight conditions, respectively. In the case of harvesting studies, 98%
      flocculation efficiency was obtained for a combination of pH 10.4, temperature 45
      degrees C, 200 mg/l of leaf powder of Cassia auriculata. The model has an R2
      value of 0.9989. The present studies indicated that cultivation of Scenedesmus
      sp. with the optimized nutrients and harvesting conditions facilitate a platform
      for energy efficient mass cultivation.

PMID- 30281404
TI  - Recombinant NS3 Protein Induced Expression of Immune Modulatory Elements in
      Hepatic Stellate Cells During Its Fibrotic Activity.
AB  - There is a growing body of studies that show the important role of NS3 protein
      from hepatitis C virus in fibrosis. However, mechanisms of the effects of this
      protein on immune modulation of stellate cells remain to be investigated. Herein,
      the effect of NS3 protein on the expression level of suppressor of cytokine
      signaling (SOCS)1/3 and interleukin-24 (IL-24)-related genes was investigated in
      hepatic stellate cell (HSC), LX-2. Recombinant NS3 protein was added to LX-2 HSC
      culture. Leptin and standard medium treatments were also included in experiments
      as positive and negative controls, respectively. Total RNA was extracted from
      each well at 6, 12, and 24 h after NS3 addition. The expression levels of the
      fibrotic (transforming growth factor beta 1 [TGF-beta], alpha-smooth muscle actin
      [alpha-SMA], and COL1A1), inflammatory (IL-6 and IL-24), IL-20R, IL-22R, and
      immunosuppressive genes (SOCS1 and SOCS3) were evaluated by real-time polymerase
      chain reaction (PCR). Recombinant NS3 protein induced activated phenotypes of LX
      2 with a significant increase in the expression level of alpha-SMA COL1A1 (p <
      0.0001) and TGF-beta. Moreover, this exposure led to a meaningful elevation in
      the expression of IL-6. Furthermore, compared with leptin (control), after the
      stellate cell treatment with NS3, SOCS1 and SOCS3 gene expression induced at a
      comparable level. Compared with the control sample, the NS3 protein significantly
      increased the expression level of IL-24 and its related receptors, IL-20R and IL
      22R. This study not only confirmed the previously proved inflammatory and
      fibrotic effect of this protein but also indicated that high expression levels of
      SOCS1, SOCS3, and IL-24 have a significant effect on HSC activation. Therefore,
      these two molecules can be used as a potential therapeutic target candidate.

PMID- 30281406
TI  - Using the categorical data analyses in determination of dust related occupational
      diseases in mining.
AB  - Dust related occupational diseases are common in mining sector. It is important
      to identify employees who have high potential for having these diseases and to
      investigate the factors affecting disease formation. For this reason, dust and
      dust related occupational diseases should be carefully investigated in the mining
      operations. In this study, dust related occupational diseases in an open pit
      lignite mine were investigated. Firstly, dust measurements were performed and
      then, health check of all employees was implemented. The obtained data set was
      categorized by taking into account the occupation, age, experience and level of
      dust exposure of the employees. While the logistic regression analysis was
      performed to determine the probability of the diseases, hierarchical loglineer
      model was established to investigate the factors in the occurrence of the
      diseases for those employees with the disease. Therefore, the most important
      factors for the development of the diseases were determined by the hierarchical
      loglinear model.

PMID- 30281405
TI  - Chemical use in the semiconductor manufacturing industry.
AB  - BACKGROUND: The semiconductor industry is known to use a number of chemicals, but
      little is known about the exact chemicals used due to the ingredients being kept
      as a trade secret. OBJECTIVES: The objective of this study was to analyze
      chemical use using a safety data sheet (SDS) and chemical inventory provided by a
      major semiconductor company, which operated two factories (A and B). METHODS:
      Descriptive statistics were obtained on the number of chemical products and
      ingredients, photoresists, and carcinogens, classified by the International
      Agency for Research on Cancer (IARC), as well as trade secret ingredients. The
      total chemical use per year was estimated from chemical inventories mass (kg).
      RESULTS: A total of 428 and 432 chemical products were used in factories A and B,
      respectively. The number of pure chemical ingredients, after removing both trade
      secret ingredients and multiple counting, was 189 and 157 in factories A and B,
      respectively. The number of products containing carcinogens, such as sulfuric
      acid, catechol, and naphthalene was 47/428 (A) and 28/432 (B). Chemicals used in
      photolithography were 21% (A) and 26% (B) of all chemical products, and more than
      97% among them were chemicals containing trade secret ingredients. CONCLUSIONS:
      Each year, 4.3 and 8.3 tons of chemicals were used per person in factories A and
      B, respectively. Because of the high level of commercial secrecy and the use of
      many unregulated chemicals, more sustainable policies and methods should be
      implemented to address health and safety issues in the semiconductor industry.

PMID- 30281407
TI  - Effect of Zingiber officinale Roscoe essential oil in fungus control and
      deoxynivalenol production of Fusarium graminearum Schwabe in vitro.
AB  - Members of the Fusarium genus are capable of contaminating agricultural
      commodities, compromising the quality of maize and other grains, which leads to
      severe quality and yield losses. Contamination with mycotoxins is also a concern.
      Essential oils are possible alternatives to the use of synthetic pesticides for
      control of fungal contamination, as many have antifungal and anti-mycotoxigenic
      properties and are innocuous to human health. They also do not cause any sort of
      microbial resistance and do not promote environmental pollution. The aim of this
      study was to evaluate the antifungal and anti-mycotoxigenic effects of Zingiber
      officinale Roscoe essential oil (GEO) upon Fusarium graminearum Schwabe in vitro.
      The essential oil was extracted by hydrodistillation and analysed by GC/MS.
      Antifungal and anti-mycotoxigenic activities were assessed by HPLC/UV by
      quantifying ergosterol and deoxynivalenol (DON), respectively. Results indicated
      that GEO inhibited ergosterol production at a concentration of 1000 ug/mL and DON
      production at a concentration of 500 ug/mL, evidencing that the anti
      mycotoxigenic effect is independent of the antifungal effect due to its probable
      direct action upon toxin biosynthesis.

PMID- 30281408
TI  - Mir-206 partially rescues myogenesis deficiency by inhibiting CUGBP1 accumulation
      in the cell models of myotonic dystrophy.
AB  - OBJECTIVES: In this study, we aim to determine how CUG-expansion and the
      abundance of Celf1 regulates normal myocyte differentiation and reveal the role
      ofmiR-206 in myotonic dystrohy and explore a possible gene therapy vector.
      METHODS:  we set up CUG-expansion and Celf1 overexpression C2C12 cell models to
      imitate the myocyte differentiation defects of DM1, then transfected AdvmiR-206
      into cell models, tested the level of myogenic markers MyoD, MyoG, Mef2c, Celf1
      by RT-PCRand Western Blotting, detected myotube formation by myosin heavy chain
      immunostaining. Result: 3'-UTR CUG-expansion leads to myotube defects and
      impaired myoblasts differentiation. Overexpression of Celf1 inhibits myoblast
      differentiation and impairs differentiation. Knockdown of Celf1 partially rescues
      differentiation defects of myoblasts harboring CUG-expansion. miR-206
      incompletely reverses myoblast differentiation inhibition induced by CUG
      expansion and partially recuses myoblast differentiation defects induced by Celf1
      overexpression. CONCLUSIONS: Ectopic miR-206 mimicking the endogenous temporal
      patterns specifically drives a myocyte program that boosts myoblast lineages,
      likely by promoting the expression of MyoD to rectify the myogenic deficiency by
      stimulating the accumulation of Celf1. ABBREVIATIONS: DMPK: (dystrophia myotonica
      protein kinase); 3'-UTR: (3'-untranslated region); MBNL1: (muscleblind-like
      [Drosophila]); DM1: (myotonic dystrophy type 1); GFP: (green fluorescent
      protein); RT-PCR: (quantitative reverse transcriptase-polymerase chain reaction);
      shRNA: (short hairpin RNA).

PMID- 30281409
TI  - Interview with Shelley E. Taylor.
AB  - Shelley Taylor's autobiographical interview (conducted by Annual Review of
      Psychology Editor and long-time collaborator Susan Fiske) touches on some of her
      favorite ideas. For example, positive illusions: "The traditional textbook
      definition of mental health included the stipulation that people see the world
      accurately, and what we were suggesting is that actually, a lot of times, people
      don't see the world accurately. They see it with a positive spin on it." She also
      discusses how to found fields (social cognition, health psychology, and social
      neuroscience) and the challenges of boundary crossing (from social to
      biological). Her practical comments describe the joy of teaching methods, running
      a lab, and being a solo female. The interview ends with her advice to follow your
      instincts about the next big idea: "Trusting your own ideas is a very important
      way of coming up with a research program that is novel, and exciting, and that
      ultimately wins people over." Expected final online publication date for the
      Annual Review of Psychology Volume 70 is January 4, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30281410
TI  - The changes of systemic immune responses during the neuroprotection induced by
      remote ischemic postconditioning against focal cerebral ischemia in mice.
AB  - OBJECTIVE: Remote limb ischemic postconditioning (RIPostC) protects the brain
      from damage induced by transient focal ischemia/reperfusion. However, the
      underlying mechanism remains unclear. METHODS: RIPostC induced by 10 min of
      occlusion and another 10 min releasing of blood flow for three cycles in the hind
      limbs was performed immediately after the reperfusion in a focal ischemia mice
      model. Neurological scores, immune cell population in the blood, spleen and lymph
      node, and inflammatory factors in the blood and brain were analyzed 2 days after
      the reperfusion. RESULTS: Our results demonstrate that RIPostC reduced cerebral
      injuries and improved neurological functions 2 days after reperfusion. RIPostC
      significantly inhibited the reduction in the percentage of CD4 T cells in the
      spleen and lymph node, CD8 T cells in the blood and lymph node, and natural
      killer T (NKT) cells in the spleen by flow cytometry analysis. RIPostC attenuated
      the increase of B cells and NK cells in the spleen and noninflammatory monocytes
      in the blood. The cytokine assay showed that RIPostC decreased the elevation of
      IL-10, IL-6, and TNF-alpha in the blood after ischemia. The quantitative real
      time reverse transcription polymerase chain reaction (qRT-PCR) results indicated
      that the mRNA level of IL-4 in the brain increased in the middle cerebral artery
      occlusion mice after RIPostC treatment. CONCLUSIONS: The present study indicates
      that there were significant changes of inflammatory responses during the
      neuroprotection induced by RIPostC in stroke mice.

PMID- 30281411
TI  - Use of traditional and alternative healers by psychiatric patients: A descriptive
      study in urban South Africa.
AB  - This study investigates the pattern of use of traditional and alternative healers
      among psychiatric patients in Nelson Mandela Metropole. An interview schedule was
      applied to 254 subjects at six sites, enquiring about consultations with
      traditional and alternative healers in the past year. Multivariate analysis was
      performed to determine predictors of consultation. Overall, 78 (31%) of
      respondents had consulted a healer in the past year. The ethnic distribution was:
      156 (61%) Black, 53 (21%) Coloured (Mixed Race), 42 (17%) White and three (1%)
      Indian. The male to female ratio was 119 (46.85%):135 (53.14%). The healers gave
      no advice about psychiatric medication to 48 (61.5%) of consulters, 23 (29.5%)
      were told to continue their medication, four (5.1%) told to stop, and one (1.3%)
      told to stop and restart later. In multivariate models, predictors of
      consultation were being Black and of lower education. Although 45 (58%) of the
      consulters indicated that medical treatment was more helpful than the healer's,
      45 (58%) intended to consult again. Overall, 22% of consulters reported abuse by
      the healer.

PMID- 30281412
TI  - Stroke hospital admission rates in Brisbane and Queensland in 2015: Data from
      11,072 cases.
AB  - Background and aims Little data exist on the incidence of stroke in Australia.
      Our aim was to report age and sex disparities in hospital admission for stroke in
      Queensland, Australia's most populous northern state. Methods We identified all
      patients admitted to hospital in Queensland with a diagnosis of stroke from
      January to December 2015. Results Among 25,776 admissions with a diagnosis of
      stroke or TIA and related sequelae, stroke was the principal diagnosis in 11,072
      cases of whom 5270 (47.60%) were first-ever stroke. Based on incidents per
      100,000 population per year, the crude annual admission rate for first-ever
      strokes was 110 (95% CI, 107 to 113), 120 (95% CI, 115 to 124) for men and 101
      (95% CI, 97 to 105) for women. The corresponding rates adjusted to the world
      population were 69 (95% CI, 52 to 85), and 88 (95% CI, 70 to 107) adjusted to the
      European population. Gender and age-adjusted incidence was greater for men than
      women in all age-groups, except those aged 30-34 years, where occurrence was 10
      for men and 16 for women. Conclusions Based on the outcomes, hospital admission
      for stroke occurs less frequently in Queensland than in other regions of
      Australia. Men generally show a higher rate of hospitalization than women, with
      the notable exception of women aged 30-34, for whom the trend reverses.

PMID- 30281414
TI  - Factors associated with 1-year mortality after discharge for acute stroke: what
      matters?
AB  - OBJECTIVE: To evaluate factors associated with 1-year mortality after discharge
      for acute stroke. METHODS: In this retrospective cohort study, we studied 305
      patients with ischemic stroke or intracerebral hemorrhage discharged in
      2010/2011. We linked Get With The Guidelines(r)-Stroke clinical data with New
      York State administrative data and used multivariate regression models to examine
      variables related to 1-year all-cause mortality poststroke. RESULTS: The mean age
      was 68.6 +/- 14.8 years and 51.1% were women. A total of 146 (47.9%) were
      discharged directly home, 96 (31.5%) to inpatient rehabilitation facilities
      (IRFs), and 63 (20.7%) to skilled nursing facilities (SNFs). Overall, 24 (7.9%)
      patients died within 1-year post-discharge. Older age (adjusted odds ratio [OR]
      1.05, 95% confidence interval [CI] 1.00-1.10), higher National Institutes of
      Health Stroke Scale (NIHSS) on admission (OR 1.10, 95% CI 1.03-1.17), and
      discharge destination (IRF vs. home, OR 0.10, 95% CI 0.01-0.94; and SNF vs. home,
      OR 2.22, 95% CI 0.71-6.95) were factors associated with 1-year all-cause
      mortality. When ambulation status at discharge was added to the model, ambulation
      with assistance and non-ambulation were significantly associated with mortality
      (ambulatory with assistance vs. ambulatory, OR 9.42, 95% CI 1.87-47.61;
      nonambulatory vs. ambulatory, OR 12.65, 95% CI 1.89-84.89). CONCLUSIONS: While
      age and NIHSS on admission are important predictors of long-term outcomes,
      factors at discharge - ambulation status at discharge and discharge destination -
      are associated with 1-year mortality post-discharge for acute stroke and
      therefore could represent therapeutic targets to improve long-term survival in
      future studies.

PMID- 30281415
TI  - Rasch analysis of the upper-limb subscale of the stroke rehabilitation assessment
      of movement (STREAM) tool in an acute stroke cohort Rasch analysis of the upper
      limb subscale of the STREAM tool in an acute stroke population.
AB  - BACKGROUND: Stroke is a leading cause of disability worldwide. The most common
      impairment resulting from stroke is upper-limb weakness. OBJECTIVES: To determine
      the usefulness and psychometric validity of the upper-limb subscale of the STREAM
      in an acute stroke population. METHODS: Rasch Analysis, including
      unidimensionality assumption testing, determining model fit, and analysis of:
      reliability, residual correlations, and differential item functioning. RESULTS:
      125 individuals were assessed using the upper-limb subscale of the Stroke
      Rehabilitation Assessment of Movement (STREAM) tool. Rasch analysis suggests the
      STREAM is a unidimensional measure. However, when scored using the originally
      proposed method (0-2), or using the response pattern (0-5) neither variant fit
      the Rasch model (p < 0.05). Although, the reliability was good (Person-Separation
      Index - 0.847 and 0.903, respectively). Correcting for the disordered thresholds,
      and thereby producing the new scoring pattern, led to substantial improvement in
      the overall fit (chi-square probability of fit - 22%), however, the reliability
      was slightly reduced (PSI - 0.806). CONCLUSIONS: The study proposes a new scoring
      method for the upper-limb subscale of the STREAM outcome measure in the acute
      stroke population.

PMID- 30281413
TI  - Occupational health and safety in cannabis production: an Australian perspective.
AB  - The legal Australian cannabis industry has been rapidly expanding due to
      increased awareness of the plant's therapeutic potential, as well its diverse
      range of applications including biofuel, textiles, building materials, food,
      nutritional supplement, and animal feed. The objective of this paper is to
      describe the current landscape of the commercial Australian cannabis industry,
      summarise occupational health and safety (OHS) hazards in cannabis-related
      working environments, and provide suggestions for safeguarding worker health and
      well-being in this emerging industry. A comprehensive search of peer-reviewed and
      grey literature published between 1900 and 2017 was undertaken to identify case
      studies and original epidemiological research on OHS hazards associated with the
      cannabis cultivation and the manufacture of cannabis-based products. The review
      found that the majority of OHS studies were undertaken in the hemp textile
      industry during the late twentieth century, with a small number of articles
      published from a variety of occupational environments including forensic
      laboratories and recreational marijuana farms. Cannabis harvesting and initial
      processing is labour intensive, and presents a physical hazard Depending on the
      operation, workers may also be exposed to a variety of biological, chemical, and
      physical hazards including: organic dusts, bioaerosols, pollen/allergens,
      volatile organic compounds, psychoactive substances (tetrahydrocannabinol
      [THC])), noise, and ultraviolet radiation. Little research has been undertaken on
      the exposure to inhalable organic dust and other bioaerosols during the
      commercial cultivation and manufacture of cannabis-based products. Furthermore,
      there is an absence of Australian-based research and OHS guidance materials to
      help professionals develop risk management strategies in this evolving industry.
      It is recommended that: Investigation into the toxicological properties of
      cannabis dusts, specifically in relation to potential occupational exposures
      during cultivation and manufacture, should be a priority. The interim adoption of
      the respirable cotton dust exposure standard of 0.2 mg/m3 for workplace exposure
      in hemp facilities until a cannabis workplace exposure standard is developed, and
      that exposure to medicinal cannabis containing THC are kept as low as reasonably
      practicable. An industry partnership be established for the development of an
      Australian health and safety guideline for the production of medicinal cannabis
      and hemp. A classification to meet the requirements of the Global Harmonization
      Scheme should be undertaken to ensure consistency in the use of safety and risk
      phrases in cannabis-related industries.

PMID- 30281416
TI  - Poor Splice-Site Recognition in a Humanized Zebrafish Knockin Model for the
      Recurrent Deep-Intronic c.7595-2144A>G Mutation in USH2A.
AB  - The frequent deep-intronic c.7595-2144A>G mutation in intron 40 of USH2A
      generates a high-quality splice donor site, resulting in the incorporation of a
      pseudoexon (PE40) into the mature transcript that is predicted to prematurely
      terminate usherin translation. Aberrant USH2A pre-mRNA splicing could be
      corrected in patient-derived fibroblasts using antisense oligonucleotides. With
      the aim to study the effect of the c.7595-2144A>G mutation and USH2A splice
      redirection on retinal function, a humanized zebrafish knockin model was
      generated, in which 670 basepairs of ush2a intron 40 were exchanged for 557
      basepairs of the corresponding human sequence using an optimized CRISPR/Cas9
      based protocol. However, in the retina of adult homozygous humanized zebrafish,
      only 7.4% +/- 3.9% of ush2a transcripts contained the human PE40 sequence and
      immunohistochemical analyses revealed no differences in the usherin expression
      and localization between the retina of humanized and wild-type zebrafish larvae.
      Nevertheless, we were able to partially correct aberrant ush2a splicing using a
      PE40-targeting antisense morpholino. Our results indicate a clear difference in
      splice-site recognition by the human and zebrafish splicing machinery. Therefore,
      we propose a protocol in which the effect of human splice-modulating mutations is
      studied in a zebrafish-specific cell-based splice assay before the generation of
      a humanized zebrafish knockin model.

PMID- 30281417
TI  - Trunk alignment in different standing positions in healthy subjects and stroke
      patients -a comparative study with a simple method for the everyday practice.:
      Trunk alignment in healthy and stroke subjects.
AB  - OBJECTIVES: Weight-bearing (WB) on the lower extremities is an important outcome
      parameter in the rehabilitation of poststroke hemiparesis. However, the patients
      often regain this ability by compensatory movement patterns. METHODS: Our goal
      was to characterize with a simple method the trunk alignment of healthy subjects
      and stroke patients (n = 17 for both groups) during standing and following
      lateral weight shift (WS). To describe trunk alignment, five markers were placed
      on the subjects' back, and the angles of the trunk at both sides were defined by
      the lines drawn from the posterior angle of the acromion and the iliac crest on
      the same body side to the seventh thoracic spinal process. Weight distributions
      on the lower extremities during standing and lateral WS were determined with a
      force platform. RESULTS: The patients had significantly limited WB capacity on
      their paretic limb, which was accompanied with significant asymmetry in the trunk
      alignment during standing and following WS to the paretic side. DISCUSSION: Our
      results show that this patient population tends to use abnormal compensatory
      movement patterns to optimize weight shifting, and changes of trunk alignment
      play a key role in this. This should be taken into consideration during
      rehabilitation.

PMID- 30281418
TI  - Hybrid Soft-Rigid Actuators for Minimally Invasive Surgery.
AB  - Fluidic mechanisms have stimulated research and development in minimally invasive
      surgery instrumentations, because of their good performance in limited size and
      their force/torque generation with respect to other types of actuation systems.
      Fluidic solutions can be divided in two major classes: (i) elastic fluidic
      actuators and (ii) piston-cylinder actuators. Elastic fluidic actuators generate
      lower forces with smaller displacements; nevertheless, piston-cylinder solutions
      require seals, which can generate friction and require maintenance costs for a
      good reliability. The proposed solution is based on a hybrid soft-rigid
      actuation, which aims to overcome the limitations of both previous solutions
      while preserving the main advantages of the overall fluidic approach. This
      approach results in very compact, powerful, and low-cost actuators, which are
      highly customizable and adaptable to specific constraints, in medical
      applications but even beyond. This article proposes a novel design of hybrid soft
      rigid actuators to be used as basic mechanical joints for enabling pitch and roll
      degrees of freedom for a miniature robotic arm. Forces up to 1.4 N and up to 2.77
      N have been obtained for the above joints, respectively, and even better
      performance can be reached (up to 3 N) with further improvements, as demonstrated
      in this article.

PMID- 30281419
TI  - Verticillium Wilt on Fiber Flax: Symptoms and Pathogen Development In Planta.
AB  - Fiber flax (Linum usitatissimum L.), an important crop in Normandy (France), is
      increasingly affected by Verticillium wilt caused by the soilborne fungus
      Verticillium dahliae. This disease leads to nonnegligible yield losses and
      depreciated fibers that are consequently difficult to upgrade. Verticillium wilt
      is a major threat to a broad range of agriculture. In this study, susceptible
      fiber flax cultivar Adelie was infected by VdLu01 (isolated from fiber flax, this
      study) or green fluorescent protein-tagged VdLs17 (transformed and provided by
      the department of Plant Pathology, University of California, Davis). Between 3
      and 4 weeks postinoculation, wilting symptoms on leaves were first observed, with
      acropetal growth during the following weeks. Pathogen development was tracked by
      confocal laser-scanning microscopy during the asymptomatic and symptomatic
      stages. First, conidia germination led to the development of hyphae on root
      epidermis; more particularly, on the zone of cell differentiation and around
      emerging lateral roots, while the zone of cell division and the root tip were
      free of the pathogen. At 3 days postinoculation, the zone of cell differentiation
      and lateral roots were embedded into a fungal mass. Swelling structures such as
      appressoria were observed at 1 week postinoculation. At 2 weeks postinoculation
      and onward, the pathogen had colonized xylem vessels in roots, followed by the
      stem and, finally, leaves during the symptomatic stage. Additionally,
      observations of infected plants after retting in the field revealed
      microsclerotia embedded inside the bast fiber bundle, thus potentially
      contributing to weakening of fiber. All of these results provide a global account
      of V. dahliae development when infecting fiber flax.

PMID- 30281420
TI  - Epidemics and Yield Losses due to Corynespora cassiicola on Cotton.
AB  - Target spot, caused by Corynespora cassiicola, has recently emerged as a
      problematic foliar disease of cotton. This pathogen causes premature defoliation
      during boll set and maturation that can subsequently impact yield, and on certain
      cotton cultivars loss can be substantial. This study sought to better understand
      target spot epidemics and disease-incited yield losses on cotton. In order to
      establish a range of disease, varying numbers of fungicide applications were made
      to each of two cotton cultivars in each of four site-years. Target spot intensity
      was rated over several dates beginning in late July or early August and
      continuing into September. Yield of seed plus lint (seed cotton) was recorded at
      harvest. When analyzed across cultivars, a second or third fungicide application
      increased yield compared with no treatment. Lack of significant yield response
      with a single fungicide application may have been due to timing of that
      application which preceded disease onset. The cultivar PhytoGen 499 WRF had
      consistently greater defoliation than any of the three Deltapine cultivars grown
      in each site-year. However, yields of both cultivars responded similarly to the
      fungicide regimes. Yield loss models based on late August defoliation were only
      predictive at site-years where conditions favored target spot development, i.e.,
      abundant rain and moderate temperatures. Epidemic development fit the Gompertz
      growth model better than it did a logistic model. Knowledge of the underlying
      mathematical character of the epidemiology of target spot will prove useful for
      development of a predictive model for the disease.

PMID- 30281421
TI  - Influence of Cotton Root System Size on Tolerance to Rotylenchulus reniformis.
AB  - The factors that influence the ability of cotton to minimize yield loss despite
      parasitism by Rotylenchulus reniformis (i.e., tolerance) were evaluated for 12
      cotton genotypes. Reproduction of R. reniformis and total length of the root
      system were measured under greenhouse conditions, and the relationship of those
      variables to yield loss caused by R. reniformis in infested fields was evaluated.
      Values for nematodes per gram of root and root length were standardized by
      setting the genotype with greatest value as 100% and then calculating a
      percentage for each genotype. There was significant variability among genotypes
      in yield loss, resistance, and root length. Average yield loss for the genotypes
      ranged from 10.4% for IAC 26RMD to 43.2% for IMACD 5675B2RF. The least nematode
      reproduction was on IAC 26RMD, which had 49.6% of the reproduction on the
      susceptible check, Deltapine 16. The genotype with the shortest total root length
      was 34% less than the genotype with the greatest length. There was a significant
      linear relationship between percentage yield loss caused by R. reniformis and
      root length and nematodes per gram of root, both expressed as a percentage of the
      maximum, represented by the following equation: Yield loss (%) = 16.1258 -
      0.1918*(% maximum root length) + 0.3728*(% maximum eggs + vermiform/g of roots).
      We conclude that tolerance to R. reniformis in cotton is influenced by the size
      of the root system and the parasitic load on the plant (nematodes per gram of
      root). Management approaches that increase root growth may lower the parasitic
      load, thereby reducing losses in cotton to R. reniformis.

PMID- 30281422
TI  - Unsupervised Semantic-Based Aggregation of Deep Convolutional Features.
AB  - In this paper, we propose a simple but effective semantic-based aggregation (SBA)
      method. The proposed SBA utilizes the discriminative filters of deep
      convolutional layers as semantic detectors. Moreover, we propose the effective
      unsupervised strategy to select some semantic detectors to generate the "soft
      region proposals," which highlight certain discriminative pattern of objects and
      suppress the noise of background. The final global SBA representation could then
      be acquired by aggregating the regional representations weighted by the selected
      "soft region proposals" corresponding to various semantic content. Our
      unsupervised SBA is easy to generalize and achieves excellent performance on
      various tasks. We conduct comprehensive experiments and show that our
      unsupervised SBA outperforms the state-of-the-art unsupervised and supervised
      aggregation methods on image retrieval, place recognition, and cloud
      classification.

PMID- 30281423
TI  - Wrist and Finger Gesture Recognition with Single-element A-mode Ultrasound
      signal: A Comparison with Single-channel Surface Electromyogram.
AB  - With the ability to detect volumetric changes of contracting muscles, ultrasound
      (US) was a potential technique in the field of human-machine interface (HMI).
      Compared to the US imaging (B-mode US), the signal from a static single-element
      US transducer, A-mode US, was a more cost-effective and convenient way towards
      the real-world application, particularly the wearables. This study compared the
      performance of the single-channel A-mode US with single-channel surface
      electromyogram (sEMG) signals, one of the most popular signal modalities for
      wrist and finger gesture recognition. We demonstrated that A-mode US outperformed
      sEMG in six out of nine gestures recognition, while sEMG was superior to A-mode
      US on the detection of the Rest state. We also demonstrated that, through feature
      space analysis, the advantage of A-mode US over sEMG for gesture recognition was
      due to its superior ability in detecting information from deep musculature. This
      study presented the clear complementary advantages between A-mode US and sEMG,
      indicating the possibility of fusing two signal modalities for the gesture
      recognition applications.

PMID- 30281424
TI  - Deep Learning Models Unveiled Functional Difference between Cortical Gyri and
      Sulci.
AB  - It is largely unknown whether there is functional role difference between
      cortical gyral and sulcal regions. Recent advancements in neuroimaging studies
      demonstrate clear difference of structural connection profiles in gyral and
      sulcal areas, suggesting possible functional role difference in these convex and
      concave cortical regions. To explore and confirm such possible functional
      difference, we design and apply a powerful deep learning model of convolutional
      neural networks (CNN) that has been proven to be superior in learning
      discriminative and meaningful patterns on fMRI. By using the CNN model, gyral and
      sulcal fMRI signals are learned and predicted, and the prediction performance is
      adopted to demonstrate the functional difference between gyri and sulci. By using
      the Human Connectome Project (HCP) fMRI data and macaque brain fMRI data, an
      average of 83% and 90% classification accuracy has been achieved to separate
      gyral/sulcal HCP task fMRI signals at the population and individual subject level
      respectively; 81% and 86% classification accuracy for resting state fMRI signals
      at the group and individual subject level respectively. In addition, 78%
      classification accuracy has been achieved to separate gyral/sulcal resting state
      fMRI signals in macaque brains. Importantly, further analysis reveals that the
      discriminative features that are learned by CNNs to differentiate gyral/sulcal
      fMRI signals can be meaningfully interpreted, thus unveiling the fundamental
      functional difference between cortical gyri and sulci. That is, gyri are more
      global functional integration centers with simpler lower frequency signal
      components, while sulci are more local processing units with more complex higher
      frequency signal components.

PMID- 30281425
TI  - Sensitivity of shoulder musculoskeletal model predictions to muscle-tendon
      properties.
AB  - OBJECTIVE: While the sensitivity of estimated muscle forces to muscle-tendon
      properties is well documented for the lower limbs, little is known about the
      shoulder and upper limbs. The purpose of this study was to assess the sensitivity
      of estimated shoulder muscle forces and scapulohumeral joint force to muscle
      tendon properties. METHODS: One healthy male participant performed arm flexions
      and simulated throwing maneuvers. Kinematics were recorded using intra-cortical
      pins. Muscle forces were estimated using static optimization with the generic
      Delft Shoulder and Elbow in OpenSim, and scapulohumeral joint forces were
      calculated from the estimated forces. Then, variations from - 25% to +25% of the
      nominal values of the tendon slack length, the optimal fiber length, the maximal
      isometric force and the pennation angle were applied to the musculoskeletal model
      to compute affected muscle forces and scapulohumeral joint force. RESULTS: The
      variations in muscle-tendon properties led to changes up to 9.6 N or 174% in the
      muscle nominal forces. The more sensitive muscles were those that produced the
      greatest force: the rotator cuff muscles and the prime movers specific to the
      task. Among the four muscle-tendon properties, the maximal isometric force and
      the optimal fiber length had the greatest influence on the muscle force
      variability. Glenohumeral force was slightly influenced by muscle-tendon
      properties (). CONCLUSION: Generic models (i.e., those without personalization of
      muscle-tendon properties) can lead to misinterpretations of muscle force. Efforts
      should focus on the maximal isometric force and the optimal fiber length of the
      rotator cuff muscles and prime movers.

PMID- 30281426
TI  - Patient-Specific Computational Simulations of Hyperpolarized 3He MRI Ventilation
      Defects in Healthy and Asthmatic Subjects.
AB  - : Combined, medical imaging data and respiratory computer simulations may
      facilitate novel insight into pulmonary disease phenotypes, including the
      structure/function relationships within the airways. This integration may
      ultimately enable improved classification and treatment of asthma. Severe asthma
      (15% of asthmatics) is particularly challenging to treat, as these patients do
      not respond well to inhaled therapeutics. METHODS: This study combines medical
      image data with patient-specific computational models to predict gas
      distributions and airway mechanics in healthy and asthmatic subjects. We achieve
      this by integrating segmental volume defect percent (SVDP), measured from
      hyperpolarized 3He MRI and CT images, to create models of patient-specific gas
      flow within the conducting airways. Predicted and measured SVDP distributions are
      achieved when the prescribed resistances are increased systematically. RESULTS:
      Because of differences in airway morphology and regional function, airway
      resistances and flow structures varied between the asthmatic subjects.
      Specifically, while mean SVDP was similar between the severe asthmatics (4.30+/
      5.22 versus 3.54+/-5.98%), one subject exhibited abnormal flow structures, high
      near wall flow gradients, and enhanced conducting airway resistances (17.3E
      3versus 1.1E-3 cmH2O-s/mL) in comparison to the other severe asthmatic subject.
      CONCLUSION: By coupling medical imaging data with computer simulations, we
      provide detailed insight into pathological flow characteristics and airway
      mechanics in asthmatics, beyond what could be inferred independently.

PMID- 30281427
TI  - Non-Contact Monitoring of Temporal Volume Changes of a Hematoma in the Head by a
      Single Inductive Coil: A Numerical Study.
AB  - OBJECTIVE: This numerical study was designed to evaluate the feasibility of using
      an inductive coil for monitoring the changes in the volume of a hematoma in the
      head in situ and to compare the inductive coil performance to that of a spiral
      antenna based on the radar principle. METHODS: Numerical analysis was used to
      solve the complete set of Maxwell's equations in full 3D anatomical model of a
      head and brain with data on clinical occurrence of hematomas from the clinical
      literature, for frequencies of 100 MHz, 500 MHz and 1 GHz. RESULTS: (1) The
      analysis shows that the spiral radar antenna provides a better resolution when
      the antenna can be placed exactly facing the center of the volume of blood. Under
      any other circumstance, the inductive coil has a better resolution at both 500
      MHz and 1 GHz. (2) The induction coil is more sensitive to rotation artifacts
      than the spiral antenna. (3) Single frequency measurements do not provide
      conclusive results. CONCLUSION: The inductive coil has the ability to monitor
      small changes in the volume of a hematoma in the head. However, multifrequency
      measurements are required for correct diagnostic. SIGNIFICANCE: This study
      provides a new, low cost alternative to conventional medical imaging for
      monitoring hematoma increase.

PMID- 30281429
TI  - Flexible Platform for In Situ Impedimetric Detection and Bioelectric Effect
      Treatment of Escherichia coli Biofilms.
AB  - GOAL: This paper reports a platform for real-time monitoring and treatment of
      biofilm formation on 3D biomedical device surfaces. METHODS: We utilize a
      flexible platform consisting of gold interdigitated electrodes patterned on a
      polyimide substrate. The device was integrated onto the interior of a urinary
      catheter and characterization was performed in a custom-developed flow system.
      Biofilm growth was monitored via impedance change at 100 Hz AC with a 50 mV
      signal amplitude. RESULTS: A 30% impedance decrease over 24 hours corresponded to
      Escherichia coli biofilm formation. The platform also enabled removal of the
      biofilm through the bioelectric effect; a low concentration of antibiotic
      combined with the applied AC voltage signal led to a synergistic reduction in
      biofilm resulting in a 12% increase in impedance. Biomass characterization via
      crystal violet staining confirmed that the impedance detection results correlate
      with changes in the amount of biofilm biomass on the sensor. We also demonstrated
      integration with a chip-based impedance converter to enable miniaturization and
      allow in situ wireless implementation. A 5% impedance decrease measured with the
      impedance converter corresponded to biofilm growth, replicating the trend
      measured with the potentiostat. CONCLUSION: This platform represents a promising
      solution for biofilm infection management in diverse vulnerable environments.
      SIGNIFICANCE: Biofilms are the dominant mode of growth for microorganisms, where
      bacterial cells colonize hydrated surfaces and lead to recurring infections. Due
      to the inaccessible nature of the environments where biofilms grow and their
      increased tolerance of antimicrobials, identification and removal on medical
      devices poses a challenge.

PMID- 30281430
TI  - Lung ultrasound surface wave elastography for assessing interstitial lung
      disease.
AB  - OBJECTIVE: Our goal is to translate lung ultrasound surface wave elastography
      (LUSWE) for assessing patients with interstitial lung disease (ILD) and various
      connective tissue diseases including systemic sclerosis (SSc). METHODS: LUSWE was
      used to measure the surface wave speed of lung at 100 Hz, 150 Hz and 200 Hz
      through six intercostal lung spaces for 91 patients with ILD and 30 healthy
      control subjects. In addition, skin viscoelasticity was measured on both forearms
      and upper arms for patients and controls. RESULTS: The surface wave speeds of
      patients' lungs were significantly higher than those of control subjects. Patient
      skin elasticity and viscosity were significantly higher than those of control
      subjects. In dividing ILD patients into two groups, ILD with SSc patients and ILD
      without SSc patients, significant differences between each patient group with the
      control group were found for both the lung and skin. No significant differences
      were found between the two patient groups, although there were some differences
      at a few locations and at 100 Hz. for skin viscoelasticity. CONCLUSION:
      Significant differences of surface wave speed were found between ILD patients and
      healthy control subjects for both the lung and skin. SIGNIFICANCE: LUSWE may be
      useful for assessing ILD and SSc and screening early stage patients.

PMID- 30281428
TI  - Three-Dimensional Brain-Computer Interface Control Through Simultaneous Overt
      Spatial Attentional and Motor Imagery Tasks.
AB  - OBJECTIVE: While noninvasive electroenceph-alography (EEG) based brain-computer
      interfacing (BCI) has been successfully demonstrated in two-dimensional (2-D)
      control tasks, little work has been published regarding its extension to
      practical three-dimensional (3-D) control. METHODS: In this study, we developed a
      new BCI approach for 3-D control by combining a novel form of endogenous
      visuospatial attentional modulation, defined as overt spatial attention (OSA),
      and motor imagery (MI). RESULTS: OSA modulation was shown to provide comparable
      control to conventional MI modulation in both 1-D and 2-D tasks. Furthermore,
      this paper provides evidence for the functional independence of traditional MI
      and OSA, as well as an investigation into the simultaneous use of both. Using
      this newly proposed BCI paradigm, 16 participants successfully completed a 3-D
      eight-target control task. Nine of these subjects further demonstrated robust 3-D
      control in a 12-target task, significantly outperforming the information transfer
      rate achieved in the 1-D and 2-D control tasks (29.7 +/- 1.6 b/min). CONCLUSION:
      These results strongly support the hypothesis that noninvasive EEG-based BCI can
      provide robust 3-D control through endogenous neural modulation in broader
      populations with limited training. SIGNIFICANCE: Through the combination of the
      two strategies (MI and OSA), a substantial portion of the recruited subjects were
      capable of robustly controlling a virtual cursor in 3-D space. The proposed novel
      approach could broaden the dimensionality of BCI control and shorten the training
      time.

PMID- 30281431
TI  - Comparison of Bipolar and Unipolar Pulses in Cell Electrofusion: Simulation and
      Experimental Research.
AB  - OBJECTIVE: Unipolar pulses have been used in cell electrofusion over the last
      decades. However, the problem of high mortality with unipolar pulses has not been
      solved effectively. The cell fusion rate is restrict by cell mortality. By using
      the advantages of bipolar pulses which cause less cell damage, this paper
      attempts to use bipolar pulses to increase the cell fusion rate. METHODS: The
      transmembrane voltage and pore density of cells subjected to unipolar/bipolar
      pulses were simulated in COMSOL software. In an experiment, two 40 MUs unipolar
      and two 20 MUs-20 MUs bipolar pulses with electric fields of 2 kV/cm, 2.5 kV/cm,
      and 3 kV/cm were applied to SP2/0 murine myeloma cells. To determine the cell
      fusion rate and cell mortality, cells were stained with Hoechst 33342 and
      propidium iodide. RESULTS: The simulation in this paper showed that a high
      transmembrane voltage and a high pores density were concentrated only at the
      contact area of cells when bipolar pulses were used. The results of the cell
      staining experiment verified the simulation analysis. When bipolar pulses were
      applied, the cell mortality was significantly reduced. In addition, the cell
      fusion rate with bipolar pulses was almost two times higher than that with
      unipolar pulses. CONCLUSION: For cell electrofusion, compared with unipolar
      pulses, bipolar pulses can not only reduce the cell mortality remarkably but also
      improve the cell fusion rate obviously. SIGNIFICANCE: This article introduces a
      novel way to increase the fusion rate of cells.

PMID- 30281432
TI  - Reconstruction of Fluorescence Molecular Tomography via a Fused LASSO Method
      Based on Group Sparsity Prior.
AB  - OBJECTIVE: The aim of this study is to improve the reconstruction accuracy in
      both position and source region of fluorescence molecular tomography (FMT).
      METHODS: The reconstruction of FMT is challenging due to its serious ill
      posedness and ill-condition. Currently, to obtain the fluorescent sources
      accurately, more a priori information of the fluorescent sources is utilized and
      more efficient and practical methods are proposed. In this paper, we took the
      group sparsity of the fluorescent sources as a new type of priori information in
      FMT, and proposed the fused LASSO method (FLM) for FMT. The FLM based on group
      sparsity prior not only takes advantage of the sparsity of the fluorescent
      sources, but also utilizes the structure of the sources, thus making the
      reconstruction results more accuracy and morphologically similar to the sources.
      To further improve the reconstruction efficiency, we adopt Nesterov's method to
      solve the FLM. RESULTS: Both heterogeneous numerical simulation experiments and
      in vivo mouse experiments were carried out to verify the property of FLM. The
      results have verified the superiority of FLM over conventional methods in tumor
      detection and tumor morphological reconstruction. Furthermore, the in vivo
      experiments had demonstrated that the FLM has great potential in preclinical
      application of FMT. SIGNIFICANCE: The reconstruction method based on group
      sparsity prior has a great potential in FMT study, it can further improve the
      reconstruction quality, which has practical significance in preclinical research.

PMID- 30281433
TI  - Optogenetic excitation of ipsilesional sensorimotor neurons is protective in
      acute ischemic stroke: a laser speckle imaging study.
AB  - OBJECTIVE: Directly modulating targeted cortical function, brain stimulation
      provides promising techniques for stroke intervention. However, the cellular
      level mechanisms underlying preserved neurovascular function remains unclear.
      Optogenetics provides cell-specific approach to modulate neuronal activity. This
      study aims to investigate whether the exclusive excitation of sensorimotor
      neurons using optogenetics in acute stroke can protect neurovascular function and
      reduce infarct size. METHODS: Sensorimotor neurons were transfected with
      channelrhodopsin-2 and excited by 473 nm laser. Photothrombotic stroke was
      induced in the ipsilateral parietal cortex and the targeted area for modulation
      remained intact. Optogenetic stimulation was carried out within 2 hrs after
      stroke in the modulation group. Using laser speckle contrast imaging technique,
      we measured the cerebral blood flow at baseline, 0 hr, 2hrs and 24 hrs after
      stroke, and analyzed the hemodynamic changes in both modulation (n=12) and
      control (n=9) groups. Also, neurovascular response was measured 24 hrs after
      stroke. RESULTS: We found that neuronal-specific excitation of ipsilesional
      sensorimotor cortex at acute stage could reduce the expansion of ischemic area
      and promote the neurovascular response at 24 hrs after stroke. The histological
      and behavioral results consolidate the protective effects of optogenetic-guided
      neuronal modulation in acute stroke. CONCLUSION: Excitatory stimulation of
      ipsilesional sensorimotor neurons in acute stroke could protect neurovascular
      function and reduces expansion of ischemic area. SIGNIFICANCE: For the first
      time, this work demonstrates that specific neuronal modulation in acute stroke is
      neuroprotective and reduces infarct size.

PMID- 30281434
TI  - Localization of Activation Origin on Patient-Specific Epicardial Surface by
      Empirical Bayesian Method.
AB  - OBJECTIVE: Ablation treatment of ventricular arrhythmias can be facilitated by
      pre-procedure planning aided by electrocardiographic inverse solution, which can
      help to localize the origin of arrhythmia. Our aim was to improve localization
      accuracy of the inverse solution by using a novel Bayesian approach. METHODS: The
      inverse problem of electrocardiography was solved by reconstructing epicardial
      potentials from 120 body-surface electrocardiograms and from patient-specific
      geometry of the heart and torso for 4 patients suffering from scar-related
      ventricular tachycardia who underwent epicardial catheter mapping which included
      pace-mapping. Simulations using dipole sources in patient-specific geometry were
      also performed. The proposed method, using dynamic spatio-temporal a priori
      constraints of the solution, was compared with classical Tikhonov methods based
      on fixed constraints. RESULTS: The mean localization error of the proposed method
      for all available pacing sites (n = 78) was significantly smaller than that
      achieved by Tikhonov methods; specifically, the localization accuracy for pacing
      in the normal tissue (n = 17) was 8+/-6 mm (mean+/-SD) versus 13+/-9 mm (P <
      0.00001) reported in the previous study using the same clinical data and Tikhonov
      regularization. Simulation experiments further supported these clinical findings.
      CONCLUSION: The promising results of in vivo and in silico experiments presented
      in this study provide a strong incentive to pursuing further investigation of
      data-driven Bayesian methods in solving the electrocardiographic inverse problem.
      SIGNIFICANCE: The proposed approach to localizing origin of ventricular
      activation sequence may have important applications in pre-procedure assessment
      of arrhythmias and in guiding their ablation treatment.

PMID- 30281435
TI  - Roll off displacement in ex vivo experiments of RF ablation with refrigerated
      saline solution and refrigerated deionized water.
AB  - OBJECTIVE: The recurrence rate in the treatment of liver tumors using
      radiofrequency ablation (RFA) is often related to incomplete tissue necrosis and
      consequently the limitation in the ablation volume. This paper proposes an
      ablation protocol combined with the infusion of saline solution and deionized
      water aiming at achieving a time displacement in the roll-off occurrence and
      consequently increasing the volume of ablation. METHODS: An infusion of saline
      solution and deionized water at 5  degrees C and 23  degrees C was performed to
      evaluate the influence of these liquids on the RFA procedure in ex vivo bovine
      liver pieces. The results obtained were used to propose a mathematical model of
      the roll-off phenomenon by means of systems identification techniques. RESULTS:
      The RFA combined with the infusion of saline solution 0.9% at 5  degrees C
      presented optimal results, with a time delay of the roll-off occurrence in 27.8%
      compared to pure RFA (p = 0.002) and an increase in the necrotic volume of 51.2%
      (p = 0.0002). Two Box-Jenkins models were obtained to describe the roll-off
      phenomenon: (i) pure RFA and (ii) RFA combined with the saline solution 0.9% at 5
      degrees C. CONCLUSION: The RFA therapy combined with the saline solution 0.9% at
      5 degrees C increases the time range to the roll-off occurrence, leading to
      higher necrosis volumes in ex vivo bovine liver samples. The development of a
      mathematical model to describe the roll-off behavior demonstrated that the
      transient response is improved by the infusion of the saline solution 0.9% at 5
      degrees C.

PMID- 30281436
TI  - Real-Time Blood Pressure Estimation From Force-Measured Ultrasound.
AB  - OBJECTIVE: Our objective is to create a blood pressure measurement device, which
      may provide a way to easily acquire frequent measurements. Common techniques to
      measure blood pressure include an arterial catheter, an oscillometric pressure
      cuff, or an auscultatory pressure cuff. METHODS: The approach takes as input
      ultrasound images of an artery and contact force between the ultrasound array and
      subject. A subject may perform the self-measurements. Image and force data is
      analyzed for its quality and used to provide guidance or reject poor
      measurements. Tissue motions, due to probe contact forces and pulsing blood
      pressure, are estimated from the ultrasound image. Tissues elasticities and blood
      pressure are found by optimally fitting the observed tissue motion versus applied
      forces to a table of predicted motion-pre-generated with a finite element tissue
      deformation model. The output of the optimization is an estimate of systolic and
      diastolic blood pressure, arterial stiffness, and surrounding tissue stiffness.
      RESULTS: The real-time implementation of the algorithm was validated on a cohort
      of 21 single-visit volunteers and on four volunteers self-monitored
      longitudinally. The systolic and diastolic pressures were compared to
      oscillometric cuff readings. Regression and Bland-Altman analyses were performed.
      CONCLUSION: Systolic pressure and diastolic pressure can be estimated in real
      time and by the subject using this novel non-invasive ultrasound-based method
      (systolic accuracy/precision: -5.2 mmHg/10.7 mmHg; diastolic accuracy/precision: 
      3.9/8.0 mmHg). SIGNIFICANCE: The method occupies a middle ground between the
      arterial catheter and cuff-based techniques. It has the potential to give
      calibration-free results.

PMID- 30281437
TI  - A Novel Geometric Framework on Gram Matrix Trajectories for Human Behavior
      Understanding.
AB  - In this paper, we propose a novel space-time geometric representation of human
      landmark configurations and derive tools for comparison and classification. We
      model the temporal evolution of landmarks as parametrized trajectories on the
      Riemannian manifold of positive semidefinite matrices of fixed-rank. Our
      representation has the benefit to bring naturally a second desirable quantity
      when comparing shapes - the spatial covariance - in addition to the conventional
      affine-shape representation. We derived then geometric and computational tools
      for rate-invariant analysis and adaptive re-sampling of trajectories, grounding
      on the Riemannian geometry of the underlying manifold. Specifically, our approach
      involves three steps: (1) landmarks are first mapped into the Riemannian manifold
      of positive semidefinite matrices of fixed-rank to build time-parameterized
      trajectories; (2) a temporal warping is performed on the trajectories, providing
      a geometry-aware (dis-)similarity measure between them; (3) finally, a pairwise
      proximity function SVM is used to classify them, incorporating the (dis
      )similarity measure into the kernel function. We show that such representation
      and metric achieve competitive results in applications as action recognition and
      emotion recognition from 3D skeletal data, and facial expression recognition from
      videos. Experiments have been conducted on several publicly available up-to-date
      benchmarks.

PMID- 30281438
TI  - Semi-Calibrated Photometric Stereo.
AB  - While conventional calibrated photometric stereo methods assume that light
      intensities and sensor exposures are known or unknown but identical across
      observed images, this assumption easily breaks down in practical settings due to
      individual light bulb's characteristics and limited control over sensors. This
      paper studies the effect of unknown and possibly non-uniform light intensities
      and sensor exposures among observed images on the shape recovery based on
      photometric stereo. This leads to a development of a "semi-calibrated"
      photometric stereo method, where the light directions are known but light
      intensities (and sensor exposures) are unknown. We show that the semi-calibrated
      photometric stereo becomes a bilinear problem, whose general form is difficult to
      solve, but in the photometric stereo context, there exists a unique solution for
      the surface normal and light intensities (or sensor exposures). We further show
      that there exists a linear solution method for the problem, and develop efficient
      and stable solution methods. The semicalibrated photometric stereo is
      advantageous over a conventional calibrated photometric stereo in accurate
      determination of surface normal because it relaxes the assumption of known light
      intensity ratios/sensor exposures. The experimental results show superior
      accuracy of the semi-calibrated photometric stereo in comparison to conventional
      methods in practical settings.

PMID- 30281439
TI  - Holistic CNN Compression via Low-rank Decomposition with Knowledge Transfer.
AB  - Convolutional neural networks (CNNs) have achieved remarkable success in various
      computer vision tasks, which are extremely powerful to deal with massive training
      data by using tens of millions of parameters. However, CNNs often cost
      significant memory and computation consumption, which prohibits their usage in
      resource-limited environments such as mobile or embedded devices. To address the
      above issues, the existing approaches typically focus on either accelerating the
      convolutional layers or compressing the fully-connected layers separatedly,
      without pursuing a joint optimum. In this paper, we overcome such a limitation by
      introducing a holistic CNN compression framework, termed LRDKT, which works
      throughout both convolutional and fully-connected layers. First, a low-rank
      decomposition (LRD) scheme is proposed to remove redundancies across both
      convolutional kernels and fullyconnected matrices, which has a novel closed-form
      solver to significantly improve the efficiency of the existing iterative
      optimization solvers. Second, a novel knowledge transfer (KT) based training
      scheme is introduced. To recover the accumulated accuracy loss and overcome the
      vanishing gradient, KT explicitly aligns outputs and intermediate responses from
      a teacher (original) network to its student (compressed) network. We have
      comprehensively analyzed and evaluated the compression and speedup ratios of the
      proposed model on MNIST and ILSVRC 2012 benchmarks. In both benchmarks, the
      proposed scheme has demonstrated superior performance gains over the state-of-the
      art methods. We also demonstrate the proposed compression scheme for the task of
      transfer learning, including domain adaptation and object detection, which show
      exciting performance gains over the state-of-the-arts. Our source code and
      compressed models are available at https://github.com/ShaohuiLin/LRDKT.

PMID- 30281440
TI  - Dynamic Atlas-based segmentation and quantification of Neuromelanin-rich
      brainstem structures in Parkinson disease.
AB  - We present a dynamic atlas composed of neuromelanin-enhanced magnetic resonance
      brain images of 40 healthy subjects. The performance of this atlas is evaluated
      on the fully automated segmentation of two paired neuromelanin-rich brainstem
      healthy structures: the substantia nigra pars compacta and the locus coeruleus.
      We show that our dynamic atlas requires in average 60% less images, and therefore
      60% less computation time than a static multi-image atlas, while achieving
      similar segmentation performance. Then, we show that by applying our dynamic
      atlas, composed of healthy subjects, to the segmentation and neuromelanin
      quantification of a set of brain images of 39 Parkinson disease patients, we are
      able to find significant quantitative differences in the level of neuromelanin
      between healthy subjects and Parkinson disease patients, thus opening the door to
      the use of these structures as image biomarkers in future Computer Aided
      Diagnosis systems for the diagnosis of Parkinson disease.

PMID- 30281441
TI  - Accurate iterative FBP reconstruction method for material decomposition of dual
      energy CT.
AB  - Compared to traditional CT, dual energy CT (DECT) has the capability to improve
      material differentiation and reduce beam hardening artifacts, thus has wide
      prospects of applications. In this paper, by linearizing the polychromatic
      projections with their first order Taylor expansions, we derive an iterative
      reconstruction method for DECT. The method updates the basis material images by
      adding the residual images reconstructed from the residual projections to the
      current estimated basis material images, i.e., the iteration process of the
      proposed method is carried out in image domain, so it is applicable to both
      geometrically consistent and inconsistent projections. In addition, as the
      filtered back-projection (FBP) method is used in the reconstruction of the
      residual images, the proposed method has a high degree of parallelism. Both
      numerical simulation and real data experiments are performed, and the results
      confirm the effectiveness of the proposed reconstruction method.

PMID- 30281442
TI  - Portable Vector Flow Imaging Compared with Spectral Doppler Ultrasonography.
AB  - In this study, a vector flow imaging (VFI) method developed for a portable
      ultrasound scanner was used for estimating peak velocity values and variation in
      beam-to-flow angle over the cardiac cycle in vivo on healthy volunteers. Peak
      systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI)
      measured with VFI were compared to spectral Doppler ultrasonography (SDU).
      Seventeen healthy volunteers were scanned on the left and right common carotid
      arteries (CCAs). The standard deviation (SD) of VFI measurements averaged over
      the cardiac cycle was 7.3% for the magnitude and 3.84 degrees  for the angle.
      Bland-Altman plots showed a positive bias for the PSV measured with SDU (mean
      difference: 0.31ms-1), and Pearson correlation analysis showed a highly
      significant correlation (r = 0.6; p < 0.001). A slightly positive bias was found
      for EDV and RI measured with SDU (mean difference: 0.08ms-1 and -0.01ms-1,
      respectively). However, the correlation was low and not significant. The beam-to
      flow angle was estimated over the systolic part of the cardiac cycle, and its
      variations were for all measurements larger than the precision of the angle
      estimation. The range spanned deviations from -25.2 degrees  (-6.0 SD) to 23.7
      degrees  (4.2 SD) with an average deviation from -15.5 degrees  to 9.7 degrees .
      This can significantly affect PSV values measured by SDU as the beam-toflow angle
      is not constant and not aligned with the vessel surface. The study demonstrates
      that the proposed VFI method can be used in vivo for the measurement of PSV in
      the CCAs, and that angle variations across the cardiac cycle can lead to
      significant errors in SDU velocity estimates.

PMID- 30281444
TI  - Fast Segmentation of the Left Atrial Appendage in 3D Transesophageal
      Echocardiographic Images.
AB  - Left atrial appendage (LAA) has been generally described as "our most lethal
      attachment", being considered the major source of thromboembolism in patients
      with non-valvular atrial fibrillation. Currently, LAA occlusion can be offered as
      a treatment for these patients, obstructing the LAA through a percutaneously
      delivered device. Nevertheless, correct device sizing is not straightforward,
      requiring the manual analysis of peri-procedural images. This approach is sub
      optimal, time demanding and highly variable between experts, which can result in
      lengthy procedures and excess manipulations. In this article, a semi-automatic
      LAA segmentation technique for 3D transesophageal echocardiography (TEE) images
      is presented. Specifically, the proposed technique relies on a novel segmentation
      pipeline where a curvilinear blind-ended model is optimized through a double
      stage strategy: 1) fast contour evolution using global terms and 2) contour
      refinement based on regional energies. To reduce its computational cost, and thus
      make it more attractive to real interventions, the B-spline Explicit Active
      Surface framework was used. This novel method was evaluated in a clinical
      database of 20 patients. Manual analysis performed by two observers was used as
      ground truth. The 3D segmentation results corroborated the accuracy, robustness
      to the variation of the parameters and computationally attractiveness of the
      proposed method, taking approximately 14 seconds to segment the LAA with an
      average accuracy of ~0.9 mm. Moreover, a performance comparable to the inter
      observer variability was found. Finally, the advantages of the segmented model
      were evaluated while semi-automatically extracting the clinical measurements for
      device selection, showing a similar accuracy but with a higher reproducibility
      when compared to the current practice. Overall, the proposed segmentation method
      shows potential for an improved planning of LAA occlusion, demonstrating its
      added value for normal clinical practice.

PMID- 30281443
TI  - Soft-Tissue Aberration Correction for Histotripsy.
AB  - Acoustic aberrations caused by natural heterogeneities of biological soft tissue
      are a substantial problem for histotripsy, a therapeutic ultrasound technique
      that uses acoustic cavitation to mechanically fractionate and destroy unwanted
      target tissue without damaging surrounding tissue. These aberrations, primarily
      caused by sound speed variations, result in severe defocusing of histotripsy
      pulses, thereby decreasing treatment efficacy. The gold standard for aberration
      correction (AC) is to place a hydrophone at the desired focal location to
      directly measure phase aberrations, which is a method that is infeasible in vivo.
      We hypothesized that the acoustic cavitation emission (ACE) shockwaves from the
      initial expansion of inertially cavitating microbubbles generated by histotripsy
      can be used as a point source for AC. In this study, a 500-kHz, 112-element
      histotripsy phased array capable of transmitting and receiving ultrasound on all
      channels was used to acquire ACE shockwaves. These shockwaves were first
      characterized optically and acoustically. It was found that the shockwave
      pressure increases significantly as the source changes from a single bubble to a
      dense cavitation cloud. The first arrival of the shockwave received by the
      histotripsy array was from the outer-most cavitation bubbles located closest to
      the histotripsy array. Hydrophone and ACE AC methods were then tested on ex vivo
      porcine abdominal tissue samples. Without AC, the focal pressure is reduced by
      49.7% through the abdominal tissue. The hydrophone AC approach recovered 55.5% of
      the lost pressure. Using the ACE AC method, over 20% of the lost pressure was
      recovered, and the array power required to induce cavitation was reduced by
      approximately 31.5% compared to without AC. These results supported our
      hypothesis that the ACE shockwaves coupled with a histotripsy array with transmit
      and receive capability can be used for AC for histotripsy through soft tissue.

PMID- 30281445
TI  - Directivity and Frequency-Dependent Effective Sensitive Element Size of a
      Reflectance-Based Fiber Optic Hydrophone: Predictions from Theoretical Models
      Compared with Measurements.
AB  - The goal of this work was to measure directivity of a reflectance-based fiber
      optic hydrophone at multiple frequencies and to compare it to four theoretical
      models: Rigid Baffle (RB), Rigid Piston (RP), Unbaffled (UB), and Soft Baffle
      (SB). The fiber had a nominal 105 MUm diameter core and a 125 MUm overall
      diameter (core + cladding). Directivity measurements were performed at 2.25, 3.5,
      5, 7.5, 10, and 15 MHz from +/-90 degrees  in two orthogonal planes. Effective
      hydrophone sensitive element radius was estimated by least-squares fitting the
      four models to directivity measurements using the sensitive element radius as an
      adjustable parameter. Over the range from 2.25 to 15 MHz, the average magnitudes
      of differences between the effective and nominal sensitive element radii were 59
      +/- 49% (RB), 10 +/- 5% (RP), 46 +/- 38% (UB), and 71 +/- 19% (SB). Therefore,
      directivity of a reflectance-based fiber-optic hydrophone may be best estimated
      by the RP model.

PMID- 30281446
TI  - Sparse Doppler Sensing Based on Nested Arrays.
AB  - Spectral Doppler ultrasound imaging allows visualizing blood flow by estimating
      its velocity distribution over time. Duplex ultrasound is a modality in which an
      ultrasound system is used for displaying simultaneously both B-mode images and
      spectral Doppler data. In B-mode imaging short wide-band pulses are used to
      achieve sufficient spatial resolution in the images. In contrast, for Doppler
      imaging, narrow-band pulses are preferred in order to attain increased spectral
      resolution. Thus, the acquisition time must be shared between the two sequences.
      In this work, we propose a non-uniform slow-time transmission scheme for spectral
      Doppler, based on nested arrays, which reduces the number of pulses needed for
      accurate spectrum recovery. We derive the minimal number of Doppler emissions
      needed, using this approach, for perfect reconstruction of the blood spectrum in
      a noise-free environment. Next, we provide two spectrum recovery techniques which
      achieve this minimal number. The first method performs efficient recovery based
      on the fast Fourier transform. The second allows for continuous recovery of the
      Doppler frequencies, thus avoiding off-grid error leakage, at the expense of
      increased complexity. The performance of the techniques is evaluated using
      realistic Field II simulations as well as in vivo measurements, producing
      accurate spectrograms of the blood velocities using a significantly reduced
      number of transmissions. The time gained, where no Doppler pulses are sent, can
      be used to enable the display of both blood velocities and high quality B-mode
      images at a high frame rate.

PMID- 30281447
TI  - A Dual-frequency Co-linear Array for Acoustic Angiography in Prostate Cancer
      Evaluation.
AB  - Approximately 80% of men who reach 80-years of age will have some form of
      prostate cancer. The challenge remains to differentiate benign and malignant
      lesions. Based on recent research, acoustic angiography, a novel contrast
      enhanced ultrasound imaging technique, can provide high-resolution visualization
      of tissue microvasculature and has demonstrated the ability to differentiate
      vascular characteristics between healthy and tumor tissue in preclinical studies.
      We hypothesize that transrectal acoustic angiography may enhance the assessment
      of prostate cancer. In this paper, we describe the development of a dual
      frequency, dual-layer co-linear array transducer for transrectal acoustic
      angiography. The probe consists of 64 transmitting (TX) elements with a center
      frequency of 3 MHz and 128 receiving (RX) elements with a center frequency of 15
      MHz. The dimensions of the array are 18 mm in azimuth and 9 mm in elevation. The
      pitch is 280 MUm for TX elements and 140 MUm for RX elements. Pulse-echo tests of
      TX/RX elements and aperture acoustic field measurements were conducted, and the
      both results were compared with simulation results. Real-time contrast imaging
      was performed using a Verasonics system and a tissue-mimicking phantom. Non
      linear acoustic responses from microbubble contrast agents at a depth of 35 mm
      were clearly observed. In-vivo imaging in a rodent model demonstrated the ability
      to detect individual vessels underneath the skin. These results indicate the
      potential use of the array described herein for acoustic angiography imaging of
      prostate tumor and identification of regions of neovascularization for the
      guidance of prostate biopsies.

PMID- 30281448
TI  - Learning Effective RGB-D Representations for Scene Recognition.
AB  - Deep convolutional networks (CNN) can achieve impressive results on RGB scene
      recognition thanks to large datasets such as Places. In contrast, RGB-D scene
      recognition is still underdeveloped in comparison, due to two limitations of RGB
      D data we address in this paper. The first limitation is the lack of depth data
      for training deep learning models. Rather than fine tuning or transferring RGB
      specific features, we address this limitation by proposing an architecture and a
      twostep training approach that directly learns effective depth-specific features
      using weak supervision via patches. The resulting RGBD model also benefits from
      more complementary multimodal features. Another limitation is the short range of
      depth sensors (typically 0.5m to 5.5m), resulting in depth images not capturing
      distant objects in the scenes that RGB images can. We show that this limitation
      can be addressed by using RGB-D videos, where more comprehensive depth
      information is accumulated as the camera travels across the scenes. Focusing on
      this scenario, we introduce the ISIA RGB-D video dataset to evaluate RGB-D scene
      recognition with videos. Our video recognition architecture combines
      convolutional and recurrent neural networks (RNNs) that are trained in three
      steps with increasingly complex data to learn effective features (i.e. patches,
      frames and sequences). Our approach obtains state-of-the-art performances on RGB
      D image (NYUD2 and SUN RGB-D) and video (ISIA RGB-D) scene recognition.

PMID- 30281449
TI  - Spectral Total-Variation Local Scale Signatures for Image Manipulation and
      Fusion.
AB  - We propose a unified framework for isolating, comparing and differentiating
      objects within an image. We rely on the recently proposed total-variation
      transform, yielding a continuous, multi-scale, fully edge-preserving, local
      descriptor, referred to as spectral total-variation local scale signatures. We
      show and analyze several useful merits of this framework. Signatures are
      sensitive to size, local contrast and composition of structures; are invariant to
      translation, rotation, flip and linear illumination changes; and texture
      signatures are robust to the underlying structures. We prove exact conditions in
      the 1D case. We propose several applications for this framework: saliency map
      extraction for fusion of thermal and optical images or for medical imaging,
      clustering of vein-like features and size-based image manipulation.

PMID- 30281450
TI  - A Probabilistic Approach to Cross-Region Matching-Based Image Retrieval.
AB  - With deep convolutional features, cross-region matching (CRM) has recently shown
      superior performance on image retrieval. It evaluates image similarity by
      comparing image regions at different locations and scales, and is, therefore,
      more robust to geometric variance of objects. This paper first scrutinizes CRM
      based image retrieval to provide a rigorous probabilistic interpretation by
      following the probability ranking principle. In addition to manifesting the
      assumptions implicitly taken by CRM, our interpretation highlights a fundamental
      issue hindering the performance of CRM-when comparing two image regions, CRM
      ignores modeling the distribution of the visual concept class associated with an
      image region, making the similarity comparison less precise. Taking advantage of
      the unprecedented representation capability of deep convolutional features, this
      paper proposes one approach to tackle that issue. It treats locally clustered
      image regions as a pseudo-labeled class sharing the same visual concept and
      utilizes them to model the distribution of the visual concept class associated
      with an image region. Both non-parametric and parametric methods are developed
      for this purpose, with careful probabilistic justification. Extensive
      experimental study on multiple benchmark data sets demonstrates the superior
      performance of the proposed pseudo-label approach to CRM and other comparable
      methods, with the maximum improvement of more than 10 percentage points over CRM.

PMID- 30281451
TI  - DeepISP: Towards Learning an End-to-End Image Processing Pipeline.
AB  - We present DeepISP, a full end-to-end deep neural model of the camera image
      signal processing (ISP) pipeline. Our model learns a mapping from the raw low
      light mosaiced image to the final visually compelling image and encompasses low
      level tasks such as demosaicing and denoising as well as higher-level tasks such
      as color correction and image adjustment. The training and evaluation of the
      pipeline were performed on a dedicated dataset containing pairs of low-light and
      well-lit images captured by a Samsung S7 smartphone camera in both raw and
      processed JPEG formats. The proposed solution achieves state-of-the-art
      performance in objective evaluation of PSNR on the subtask of joint denoising and
      demosaicing. For the full end-to-end pipeline, it achieves better visual quality
      compared to the manufacturer ISP, in both a subjective human assessment and when
      rated by a deep model trained for assessing image quality.

PMID- 30281452
TI  - Graph-Based Joint Dequantization and Contrast Enhancement of Poorly Lit JPEG
      Images.
AB  - JPEG images captured in poor lighting conditions suffer from both low luminance
      contrast and coarse quantization artifacts due to lossy compression. Performing
      dequantization and contrast enhancement in separate back-to-back steps would
      amplify the residual compression artifacts, resulting in low visual quality.
      Leveraging on recent development in graph signal processing (GSP), we propose to
      jointly dequantize and contrast-enhance such images in a single graph-signal
      restoration framework. Specifically, we separate each observed pixel patch into
      illumination and reflectance via Retinex theory, where we define generalized
      smoothness prior and signed graph smoothness prior according to their respective
      unique signal characteristics. Given only a transform-coded image patch, we
      compute robust edge weights for each graph via low-pass filtering in the dual
      graph domain. We compute the illumination and reflectance components for each
      patch alternately, adopting accelerated proximal gradient (APG) algorithms in the
      transform domain, with backtracking line search for further speedup. Experimental
      results show that our generated images outperform the state-of-the-art schemes
      noticeably in the subjective quality evaluation.

PMID- 30281453
TI  - Learning a Convolutional Neural Network for Image Compact-Resolution.
AB  - We study the dual problem of image super-resolution (SR), which we term image
      compact-resolution (CR). Opposite to image SR that hallucinates a visually
      plausible high-resolution image given a low-resolution input, image CR provides a
      low-resolution version of a high-resolution image, such that the low-resolution
      version is both visually pleasing and as informative as possible compared to the
      high-resolution image. We propose a convolutional neural network (CNN) for image
      CR, namely, CNN-CR, inspired by the great success of CNN for image SR.
      Specifically, we translate the requirements of image CR into operable
      optimization targets for training CNN-CR: the visual quality of the compact
      resolved image is ensured by constraining its difference from a naively
      downsampled version and the information loss of image CR is measured by
      upsampling/super-resolving the compact-resolved image and comparing that to the
      original image. Accordingly, CNN-CR can be trained either separately or jointly
      with a CNN for image SR. We explore different training strategies as well as
      different network structures for CNN-CR. Our experimental results show that the
      proposed CNN-CR clearly outperforms simple bicubic downsampling and achieves on
      average 2.25 dB improvement in terms of the reconstruction quality on a large
      collection of natural images. We further investigate two applications of image
      CR, i.e., low-bit-rate image compression and image retargeting. Experimental
      results show that the proposed CNN-CR helps achieve significant bits saving than
      High Efficiency Video Coding when applied to image compression and produce
      visually pleasing results when applied to image retargeting.

PMID- 30281454
TI  - Multi-Domain & Multi-Task Learning for Human Action Recognition.
AB  - Domain-invariant (view-invariant & modalityinvariant) feature representation is
      essential for human action recognition. Moreover, given a discriminative visual
      representation, it is critical to discover the latent correlations among multiple
      actions in order to facilitate action modeling. To address these problems, we
      propose a multi-domain & multi-task learning (MDMTL) method to (1) extract domain
      invariant information for multi-view and multi-modal action representation and
      (2) explore the relatedness among multiple action categories. Specifically, we
      present a sparse transfer learning-based method to co-embed multi-domain (multi
      view & multi-modality) data into a single common space for discriminative feature
      learning. Additionally, visual feature learning is incorporated into the
      multitask learning framework, with the Frobenius-norm regularization term and the
      sparse constraint term, for joint task modeling and task relatedness-induced
      feature learning. To the best of our knowledge, MDMTL is the first supervised
      framework to jointly realize domain-invariant feature learning and task modeling
      for multi-domain action recognition. Experiments conducted on the INRIA Xmas
      Motion Acquisition Sequences (IXMAS) dataset, the MSR Daily Activity 3D
      (DailyActivity3D) dataset, and the Multi-modal & Multi-view & Interactive (M2I)
      dataset, which is the most recent and largest multi-view and multi-model action
      recognition dataset, demonstrate the superiority of MDMTL over the state-of-the
      art approaches.

PMID- 30281455
TI  - MSFD: Multi-Scale Segmentation-Based Feature Detection for Wide-Baseline Scene
      Reconstruction.
AB  - A common problem in wide-baseline matching is the sparse and non-uniform
      distribution of correspondences when using conventional detectors, such as SIFT,
      SURF, FAST, A-KAZE, and MSER. In this paper, we introduce a novel segmentation
      based feature detector (SFD) that produces an increased number of accurate
      features for wide-baseline matching. A multi-scale SFD is proposed using
      bilateral image decomposition to produce a large number of scale-invariant
      features for wide-baseline reconstruction. All input images are over-segmented
      into regions using any existing segmentation technique, such as Watershed, Mean
      shift, and simple linear iterative clustering. Feature points are then detected
      at the intersection of the boundaries of three or more regions. The detected
      feature points are local maxima of the image function. The key advantage of
      feature detection based on segmentation is that it does not require global
      threshold setting and can, therefore, detect features throughout the image. A
      comprehensive evaluation demonstrates that SFD gives an increased number of
      features that are accurately localized and matched between wide-baseline camera
      views; the number of features for a given matching error increases by a factor of
      3-5 compared with SIFT; feature detection and matching performance are maintained
      with increasing baseline between views; multi-scale SFD improves matching
      performance at varying scales. Application of SFD to sparse multi-view wide
      baseline reconstruction demonstrates a factor of 10 increases in the number of
      reconstructed points with improved scene coverage compared with SIFT/MSER/A-KAZE.
      Evaluation against ground-truth shows that SFD produces an increased number of
      wide-baseline matches with a reduced error.

PMID- 30281456
TI  - Zero-Shot Learning via Category-Specific Visual-Semantic Mapping and Label
      Refinement.
AB  - Zero-Shot Learning (ZSL) aims to classify a test instance from an unseen category
      based on the training instances from seen categories, in which the gap between
      seen categories and unseen categories is generally bridged via visual-semantic
      mapping between the low-level visual feature space and the intermediate semantic
      space. However, the visual-semantic mapping (i.e., projection) learnt based on
      seen categories may not generalize well to unseen categories, which is known as
      the projection domain shift in ZSL. To address this projection domain shift
      issue, we propose a method named Adaptive Embedding ZSL (AEZSL) to learn an
      adaptive visual-semantic mapping for each unseen category, followed by
      progressive label refinement. Moreover, to avoid learning visual-semantic mapping
      for each unseen category in the large-scale classification task, we additionally
      propose a deep adaptive embedding model named Deep AEZSL (DAEZSL) sharing the
      similar idea (i.e., visual-semantic mapping should be category-specific and
      related to the semantic space) with AEZSL, which only needs to be trained once,
      but can be applied to arbitrary number of unseen categories. Extensive
      experiments demonstrate that our proposed methods achieve the state-of-theart
      results for image classification on three small-scale benchmark datasets and one
      large-scale benchmark dataset.

PMID- 30281457
TI  - Deep Convolutional Neural Network for Natural Image Matting Using Initial Alpha
      Mattes.
AB  - We propose a deep convolutional neural network (CNN) method for natural image
      matting. Our method takes multiple initial alpha mattes of the previous methods
      and normalized RGB color images as inputs, and directly learns an end-to-end
      mapping between the inputs and reconstructed alpha mattes. Among the various
      existing methods, we focus on using two simple methods as initial alpha mattes:
      the closed-form matting and KNN matting. They are complementary to each other in
      terms of local and nonlocal principles. A major benefit of our method is that it
      can "recognize" different local image structures and then combine the results of
      local (closed-form matting) and nonlocal (KNN matting) mattings effectively to
      achieve higher quality alpha mattes than both of the inputs. Furthermore, we
      verify extendability of the proposed network to different combinations of initial
      alpha mattes from more advanced techniques such as KL divergence matting and
      information-flow matting. On the top of deep CNN matting, we build an RGB guided
      JPEG artifacts removal network to handle JPEG block artifacts in alpha matting.
      Extensive experiments demonstrate that our proposed deep CNN matting produces
      visually and quantitatively high-quality alpha mattes. We perform deeper
      experiments including studies to evaluate the importance of balancing training
      data and to measure the effects of initial alpha mattes and also consider results
      from variant versions of the proposed network to analyze our proposed DCNN
      matting. In addition, our method achieved high ranking in the public alpha
      matting evaluation dataset in terms of the sum of absolute differences, mean
      squared errors, and gradient errors. Also, our RGB guided JPEG artifacts removal
      network restores the damaged alpha mattes from compressed images in JPEG format.

PMID- 30281458
TI  - Context-Aware Text-Based Binary Image Stylization and Synthesis.
AB  - In this work, we present a new framework for the stylization of text-based binary
      images. First, our method stylizes the stroke-based geometric shape like text,
      symbols and icons in the target binary image based on an input style image.
      Second, the composition of the stylized geometric shape and a background image is
      explored. To accomplish the task, we propose legibilitypreserving structure and
      texture transfer algorithms, which progressively narrow the visual differences
      between the binary image and the style image. The stylization is then followed by
      a contextaware layout design algorithm, where cues for both seamlessness and
      aesthetics are employed to determine the optimal layout of the shape in the
      background. Given the layout, the binary image is seamlessly embedded into the
      background by texture synthesis under a context-aware boundary constraint.
      According to the contents of binary images, our method can be applied to many
      fields.We show that the proposed method is capable of addressing the unsupervised
      text stylization problem and is superior to stateof- the-art style transfer
      methods in automatic artistic typography creation. Besides, extensive experiments
      on various tasks, such as visual-textual presentation synthesis, icon/symbol
      rendering and structure-guided image inpainting, demonstrate the effectiveness of
      the proposed method.

PMID- 30281459
TI  - A Task-based Taxonomy of Cognitive Biases for Information Visualization.
AB  - Information visualization designers strive to design data displays that allow for
      efficient exploration, analysis, and communication of patterns in data, leading
      to informed decisions. Unfortunately, human judgment and decision making are
      imperfect and often plagued by cognitive biases. There is limited empirical
      research documenting how these biases affect visual data analysis activities.
      Existing taxonomies are organized by cognitive theories that are hard to
      associate with visualization tasks. Based on a survey of the literature we
      propose a task-based taxonomy of154 cognitive biases organized in 7 main
      categories. We hope the taxonomy will help visualization researchers relate their
      design to the corresponding possible biases, and lead to new research that
      detects and addresses biased judgment and decision making in data visualization.

PMID- 30281460
TI  - BRDF Analysis with Directional Statistics and Its Applications.
AB  - Data-driven BRDF models using real material measurements have become increasingly
      prevalent due to the development of novel gonioreflectometers, but efficient use
      of these models in many graphical applications remains challenging due to the few
      functionalities the raw data could provide. To ameliorate this issue, we propose
      to analyze BRDFs using directional statistics for better handling and exploring
      measured materials, especially isotropic materials, with efficient computation
      and compact storage. We conduct a thorough statistical analysis on both
      analytical BRDF models and measured materials from the MERL database. We show
      that different aspects of visual appearance can be characterized by different
      spherical moments, from which several descriptive measures can be derived to
      further facilitate their usage. We demonstrate how these measures are best
      leveraged in some graphical applications including gamut mapping using a new BRDF
      similarity measure, BRDF or SVBRDF reconstruction based on material clustering,
      and importance sampling for measured materials based on fast extracted GGX
      distributions. We finally show the potential of our approach in the
      categorization of surface reflectance types which is common for traditional
      photon mapping.

PMID- 30281461
TI  - ViSeq: Visual Analytics of Learning Sequence in Massive Open Online Courses.
AB  - The research on massive open online courses (MOOCs) data analytics has mushroomed
      recently because of the rapid development of MOOCs. The MOOC data not only
      contains learner profiles and learning outcomes, but also sequential information
      about when and which type of learning activities each learner performs, such as
      reviewing a lecture video before undertaking an assignment. Learning sequence
      analytics could help understand the correlations between learning sequences and
      performances, which further characterize different learner groups. However, few
      works have explored the sequence of learning activities, which have mostly been
      considered aggregated events. A visual analytics system called ViSeq is
      introduced to resolve the loss of sequential information, to visualize the
      learning sequence of different learner groups, and to help better understand the
      reasons behind the learning behaviors. The system facilitates users in exploring
      learning sequences from multiple levels of granularity. ViSeq incorporates four
      linked views: the projection view to identify learner groups, the pattern view to
      exhibit overall sequential patterns within a selected group, the sequence view to
      illustrate the transitions between consecutive events, and the individual view
      with an augmented sequence chain to compare selected personal learning sequences.
      Case studies and expert interviews were conducted to evaluate the system.

PMID- 30281462
TI  - Topic-based Exploration and Embedded Visualizations for Research Idea Generation.
AB  - This work analyzes sensemaking frameworks and experiments with an iteratively
      designed visual analysis tool to identify design implications for facilitating
      research idea generation using visualizations. Our tool, ThoughtFlow, structures
      and visualizes literature collections using topic models to bridge the
      information gap between core activities during research ideation. To help users
      stay focused on a topic while discovering relevant documents, we designed and
      analyzed usage patterns for two types of embedded visualization that help
      determine document relevance while minimizing distraction. We analyzed how
      research ideation outcomes and processes differ when using ThoughtFlow and
      conventional search engines by augmenting insight-based evaluation with concept
      map analysis. Our results suggest that operations afforded by topic models match
      well with later ideation stages when coherent topics have emerged, but not with
      early stages when users are still relying heavily on individual keywords to
      gather background knowledge. We also present qualitative evidence that citation
      sparklines encourage more exploration of recommended references, and that a
      preference for paper thumbnails may depend on the consistency between the
      evidence and the current mental frame.

PMID- 30281463
TI  - A Novel CNN-based Poisson Solver for Fluid Simulation.
AB  - Solving a large-scale Poisson system is computationally expensive for most of the
      Eulerian fluid simulation applications. We propose a novel machine learning-based
      approach to accelerate this process. At the heart of our approach is a deep
      convolutional neural network (CNN), with the capability of predicting the
      solution (pressure) of a Poisson system given the discretization structure and
      the intermediate velocities as input. Our system consists of four main
      components, namely, a deep neural network to solve the large linear equations, a
      geometric structure to describe the spatial hierarchies of the input vector, a
      Principal Component Analysis (PCA) process to reduce the dimension of input in
      training, and a novel loss function to control the incompressibility constraint.
      We have demonstrated the efficacy of our approach by simulating a variety of high
      resolution smoke and liquid phenomena. In particular, we have shown that our
      approach accelerates the projection step in a conventional Eulerian fluid
      simulator by two orders of magnitude. In addition, we have also demonstrated the
      generality of our approach by producing a diversity of animations deviating from
      the original datasets.

PMID- 30281464
TI  - Comparison of Convolutive Kernel Compensation and Non-Negative Matrix
      Factorization of Surface Electromyograms.
AB  - We compared non-negative matrix factorization (NMF) and convolution kernel
      compensation techniques for high-density electromyogram decomposition. The
      experimental data were recorded from nine healthy persons during controlled
      single degree of freedom (DOF) wrist flexion-extension, supination-pronation, and
      ulnar-radial deviation movements. We assembled the identified motor units and NMF
      components into three groups. Those active mostly during the first and the second
      movement direction per DOF were placed in the G1 and G3 groups, respectively. The
      remaining components were nonspecific for movement direction and were placed in
      the G2 group. In ulnar and radial deviation, the relative energies of identified
      cumulative motor unit spike trains (CSTs) and NMF components were similarly
      distributed among the groups. In other two movement types, the energy of NMF
      components in the G2 group was significantly larger than the energy of CSTs. We
      further performed a coherence analysis between CSTs and sums of NMF components in
      each group. Both decompositions demonstrated a solid match, but only at
      frequencies <3 Hz. At higher frequencies, the coherence hardly exceeded the value
      of 0.5. Potential reasons for these discrepancies include the negative impact of
      motor unit action potential shapes and noise on NMF decomposition.

PMID- 30281465
TI  - A Fatigue Involved Modification Framework for Force Estimation in Fatiguing
      Contraction.
AB  - To alleviate the negative impacts of muscle fatigue on a force estimation model,
      a modification framework taking use of fatigue index was put forward in this
      paper. Muscle force and surface electromyography were first collected using high
      density electrode grid and dynamometer. Then, multi-step signal pre-processing
      and a nonnegative matrix factorization-based signal optimization were conducted,
      with fatigue indices being extracted in the same time. Next, a degree 4
      polynomial fitting model was employed to undertake the training process, and the
      relationship between the generated model parameters and fatigue indices was built
      up. In the end, the parameter-index relationship was applied on different testing
      sets to complete fatigue-modified force estimation. Significant improvement was
      found in most testing cases across different sexes and ages. Relative decreases
      of 36.5%, 20.7%, and 20.4% in the percentage root mean square error were achieved
      by young males, young females, and elderly males. The proposed method can boost
      the performances of force estimation models, thereby contributing to the
      development of a variety of fields including biomechanical study, rehabilitation
      treatment, and prosthesis research.

PMID- 30281466
TI  - Reducing the Energy Cost of Human Running Using an Unpowered Exoskeleton.
AB  - In this paper, we present a new perspective to design an unpowered exoskeleton
      for metabolic rate reduction in running. According to our studies on human
      biomechanics, it was observed that having a torsional spring that applies torque
      as a linear function of the difference between two hips angles ( -angle),
      compared with a local spring which applies torque as a function of hip angle ( 
      angle), provides a better condition for hip moment compensation and,
      consequently, metabolic rate reduction. Accordingly, a new type of unpowered
      exoskeleton device for realization of this idea was designed, and a prototype of
      this exoskeleton was constructed. This exoskeleton was tested on 10 healthy
      active subjects for running at 2.5 m s-1. In this experiment, 8.0 +/- 1.5% (mean
      +/- s.e.m.) metabolic rate reduction (compared with the no-exoskeleton case) was
      achieved.

PMID- 30281467
TI  - STEW: Simultaneous Task EEG Workload Data Set.
AB  - This paper describes an open access electroencephalography (EEG) data set for
      multitasking mental workload activity induced by a single-session simultaneous
      capacity (SIMKAP) experiment with 48 subjects. To validate the database, EEG
      spectral activity was evaluated with EEGLAB and the significant channels and
      activities for the experiment are highlighted. Classification performance was
      evaluated by training a support vector regression model on selected features from
      neighborhood component analysis based on a nine-point workload rating scale. With
      a reduced feature dimension, 69% classification accuracy was obtained for 3
      identified workload levels from the rating scale with Cohen's kappa of 0.46.
      Accurate discrimination of mental workload is a desirable outcome in the field of
      operator performance analysis and BCI development; thus, we hope that our
      provided database and analyses can contribute to future investigations in this
      research field.

PMID- 30281468
TI  - simBCI - A framework for studying BCI methods by simulated EEG.
AB  - Brain-Computer Interface (BCI) methods are commonly studied using
      Electroencephalogram (EEG) data recorded from human experiments. For
      understanding and developing BCI signal processing techniques real data is costly
      to obtain and its composition is apriori unknown. The brain mechanisms generating
      the EEG are not directly observable and their states cannot be uniquely
      identified from the EEG. Subsequently, we do not have generative ground truth for
      real data. In this paper we propose a novel convenience framework called simBCI
      to alleviate testing and studying BCI signal processing methods in simulated,
      controlled conditions. The framework can be used to generate artificial BCI data
      and to test classification pipelines with such data. Models and parameters on
      both data generation and the signal processing side can be iterated over to
      examine the interplay of different combinations. The framework provides the first
      time open source implementations of several models and methods. We invite
      researchers to insert more advanced models. The proposed system does not intend
      to replace human experiments. Instead, it can be used to discover hypotheses,
      study algorithms, to educate about BCI, and to debug signal processing pipelines
      of other BCI systems. The proposed framework is modular, extensible and freely
      available as open source1. It currently requires Matlab.

PMID- 30281469
TI  - A Modeling Procedure of the Broadband Dielectric Spectroscopy for Ionic Liquids.
AB  - The dielectric spectroscopy (DS) measurement is an attractive noninvasive method
      to reveal the intrinsic information of biological materials and cell cultures.
      However, the presence of a double layer due to electrode polarization within the
      lower RF and microwave range significantly affects the accurate analysis of
      dielectric properties of ionic liquids. In this paper, we measure the broadband
      DS of five saline solutions with a microfluidic coplanar waveguide (CPW)
      transmission line sensor across the frequency range from 40 kHz to 110 GHz.
      Derived from a parallel-plate structure that is transformed from the quasi-TEM
      CPW sensor through a conformal mapping technique, a broadband spectroscopy
      modeling method is proposed, where a Cole-Cole function or a constant phase
      element formula is used depending on the ionic concentrations and the measurement
      window. Validation analysis on the five saline solutions demonstrates the
      capability of the modeling method in separating relaxation properties of the bulk
      sample from the double-layer effects.

PMID- 30281470
TI  - Modeling and Dynamic Behavior of eIF2 Dependent Regulatory System With
      Disturbances.
AB  - Eukaryotic initiation factor 2 (eIF2) is a central controller of the eukaryotic
      translational machinery. To sustain the on-going translation activity, eIF2
      cycles between its GTP and GDP bound states. However, in response to cellular
      stresses, the phosphorylation of eIF2 takes place, which acts as an inhibitor of
      the guanine nucleotide exchange factor eIF2B and switches the translation
      activity on physiological timescales. The main objective of this paper is to
      investigate the stability of the regulatory system under nominal conditions,
      parametric fluctuations, and structural damages. In this paper, a mathematical
      model of eIF2-dependent regulatory system is used to identify the stability
      conferring features within the system with the help of direct and indirect
      methods of Lyapunov stability theory. To investigate the impact of intrinsic
      fluctuations and structural damages on the stability of regulatory system, the
      mathematical model has been linearized around feasible equilibrium point and the
      variation of system poles has been observed. The investigations have revealed
      that the regulatory model is stable and able to tolerate the intrinsic stressors
      but becomes unstable when particular complex is targeted to override the
      undesirable interaction. Our analyses indicate that, the stability is a
      collective property and damage in the structure of the system changes the
      stability of the system.

PMID- 30281471
TI  - A Parallel Workflow Pattern Modeling Using Spiking Neural P Systems With Colored
      Spikes.
AB  - Spiking neural P systems, otherwise known as named SN P systems, are bio-inspired
      parallel and distributed neural-like computing models. Due to the spiking
      behavior, SN P systems fall into the category of spiking neural networks, and are
      considered to be an auspicious candidate of the 3G of neural networks. It has
      been reported that SN P systems with colored spikes are computationally capable,
      and perform well in describing behaviors of complex systems. Nonetheless, some
      practical issue is open to be investigate, such as workflow and traffic flow
      modeling. In this paper, a parallel workflow pattern modeling using SN P systems
      with colored spikes is proposed. As results, 20 designs are constructed using SN
      P systems for 20 classical workflow patterns. The functioning processes that
      operate both sequentially and simultaneously in the workflow pattern are able to
      be modeled and simulated. SN P systems with colored spikes have some similarity
      with Petri nets, hence can be used to model workflow patterns. This will provide
      a novel neural-like modeling method for modeling traffic flow.

PMID- 30281472
TI  - ASAPP: Architectural Similarity-based Automated Pathway Prediction System and its
      Application in Host-Pathogen Interactions.
AB  - The significance of metabolic pathway prediction is to envision the viable
      unknown transformations that can occur provided the appropriate enzymes are
      present. It can facilitate the prediction of the consequences of host-pathogen
      interactions. In this article, we have proposed a new algorithm ASAPP
      (Architectural Similarity-based Automated Pathway Prediction) to predict
      metabolic pathways based on the structural similarity among the metabolites.
      ASAPP takes two dimensional structure and molecular weight of metabolites as
      input, and generates a list of probable transformations without the knowledge of
      any externally established reactions, with an accuracy of 85.09%. ASAPP has also
      been applied to predict the outcome of pathogen liberated toxins on the
      carbohydrate and lipid pathways of the hosts. We have analyzed the disruption of
      host pathways in the presence of toxins, and have found that some metabolites in
      Glycolysis and the TCA cycle have a high chance of being the breakpoints in the
      pathway. The tool is available at http://asapp.droppages.com/.

PMID- 30281473
TI  - In Silico Design and Experimental Validation of Combination Therapy for
      Pancreatic Cancer.
AB  - The number of deaths associated with Pancreatic Cancer has been on the rise in
      the United States making it an especially dreaded disease. The overall prognosis
      for pancreatic cancer patients continues to be grim because of the complexity of
      the disease at the molecular level involving the potential
      activation/inactivation of several diverse signaling pathways. In this paper, we
      first model the aberrant signaling in pancreatic cancer using a multi-fault
      Boolean Network. Thereafter, we theoretically evaluate the efficacy of different
      drug combinations by simulating this boolean network with drugs at the relevant
      intervention points and arrive at the most effective drug(s) to achieve cell
      death. The simulation results indicate that drug combinations containing
      Cryptotanshinone, a traditional Chinese herb derivative, result in considerably
      enhanced cell death. These in silico results are validated using wet lab
      experiments we carried out on Human Pancreatic Cancer (HPAC) cell lines.

PMID- 30281474
TI  - Inferring disease-associated microRNAs in heterogeneous networks with node
      attributes.
AB  - Identification of disease-associated microRNAs (disease miRNAs) is an essential
      step towards discovering causal miRNAs and understanding disease pathogenesis.
      Two sources of information can be exploited for predicting disease miRNAs: one
      includes the connections between miRNAs, between diseases, and between miRNAs and
      diseases, and the other has the attributes of miRNA nodes. The former contains
      information of miRNA similarities, disease similarities, and miRNA-disease
      associations. The latter includes the information of the families and clusters
      that miRNAs belong to. Similar diseases are usually associated with miRNAs that
      have similar functions and common attributes. However, most of the existing
      methods for disease miRNA prediction focus only on the connections of miRNAs and
      diseases. It remains challenging to adequately integrate the connections and
      miRNA node attributes to identify more reliable candidate disease miRNAs. We
      propose a non-negative matrix factorization based method, FamCluRank, for
      predicting disease miRNAs in heterogeneous networks with node attributes. One of
      the novelties of FamCluRank is to fully utilize these two oversighted
      characteristics of miRNAs and focuses particularly on a deep integration of miRNA
      families and cluster attributes. In particular, the integration was achieved by
      three different means. We first constructed a miRNA-disease heterogeneous network
      with node attributes where the miRNA nodes have their family and cluster
      attributes. Second, miRNAs sharing more common families and clusters are more
      likely to be associated with the diseases that are also related to these families
      and clusters. On the basis of the biological premise, we constructed a novel
      prediction model of FamCluRank to deeply integrate the family and cluster
      attributes of miRNAs. Third, two similar diseases tend to be associated with more
      common miRNA families and clusters, and vice versa. Hence FamCluRank's prediction
      model is constructed by concerning not only the possible associations between
      miRNAs and diseases but also the possible disease-family and disease-cluster
      associations. Comparison with the state-of-the-art methods showed FamCluRank's
      superior performance not only on the well-characterized diseases but also on the
      new ones. Case studies on colorectal neoplasms, pancreatic neoplasms, lung
      neoplasms, and 32 new diseases demonstrated its ability for discovering potential
      disease miRNAs. FamCluRank is a potent prioritization tool for screening the
      reliable candidates for subsequent studies concerning their involvement in the
      pathogenesis of diseases. The web service of FamCluRank, the candidate disease
      miRNAs for 329 diseases, and the dataset used to develop FamCluRank are available
      at http://www.famclurank.top.

PMID- 30281475
TI  - Enhancing of Particle Swarm Optimization Based Method for Multiple Motifs
      Detection in DNA Sequences Collections.
AB  - Genome sequence data consists of DNA sequences or input sequences. Each one
      includes nucleotides with chemical structures presented as characters: 'A', 'C',
      'G', and 'T', and groups of motif sequences, called Transcription Factor Binding
      Sites (TFBSs), which are subsequences of DNA that lead to protein-synthesis. The
      detection of TFBSs is an important problem for bioinformatics research. With the
      similar patterns of motif sequences in TFBSs, computational algorithms for TFBSs
      detection have been improved to reduce resources used in laboratory setting. The
      metaheuristic algorithm is the important issue that has been continually improved
      to detect TFBSs with greater precision and recall. This paper proposes PSO_HD by
      applying Particle Swarm Optimization (PSO) as a pre-process and using Hamming
      distance to improve the efficiency of detecting TFBSs with more precision and
      recall. In order to measure its efficiency, the paper compares the TFBSs
      detection using PSO_HD algorithm with relevant algorithms in 8 datasets. F-score
      is used as a measurement unit and compared to the related algorithms. The
      experimental results show that PSO_HD algorithm gives the highest average F
      score, which can be indicated that the PSO_HD algorithm can improve the
      efficiency of detecting TFBSs with more precision and recall.

PMID- 30281477
TI  - Differential Expression Analysis of RNA-seq Reads: Overview, Taxonomy and Tools.
AB  - Analysis of RNA-sequence (RNA-seq) data is widely used in transcriptomic studies
      and it has many applications. We review RNA-seq data analysis from RNA-seq reads
      to the results of differential expression analysis. In addition, we perform
      descriptive comparison of tools used in each step of RNA-seq data analysis along
      with a discussion of important aspects for these tools. A taxonomy of tools is
      also provided. A discussion of issues in quality control and visualization of RNA
      seq data is also included along with useful tools. Finally, we provide some
      guidelines for the RNA-seq data analyst, along with research issues and
      challenges which should be addressed.

PMID- 30281476
TI  - Gene Regulatory Relationship Mining Using Improved Three-Phase Dependency
      Analysis Approach.
AB  - How to mine the gene regulatory relationship and construct gene regulatory
      network (GRN) is of utmost interest within the whole biological community,
      however, which has been consistently a challenging problem since the tremendous
      complexity in cellular systems. In present work, we construct gene regulatory
      network using an improved three-phase dependency analysis algorithm (TPDA)
      Bayesian network learning method, which includes the steps of Drafting,
      Thickening and Thinning. In order to solve the problem of learning result is not
      reliable due to the high order conditional independence test, we use the entropy
      estimation approach of Gaussian kernel probability density estimator to calculate
      the (conditional) mutual information between genes. The experiment on the public
      benchmark data sets show the improved method outperforms other 9 kinds of
      Bayesian network learning methods when to process the data with large sample
      size, with small number of discrete values, and the frequency of different
      discrete values is about same. In addition, the improved TPDA method was further
      applied on a real large gene expression data set on RNA-seq from a global
      collection with 368 elite maize inbred lines. Experiment results show it performs
      better than the original TPDA method and other 9 kinds of Bayesian network
      learning algorithms significantly.

PMID- 30281478
TI  - miRTRS: A Recommendation Algorithm for Predicting miRNA Targets.
AB  - microRNAs (miRNAs) are small and important non-coding RNAs that regulate gene
      expression in transcriptional and post-transcriptional level by combining with
      their targets(genes). Predicting miRNA targets is an important problem in
      biological research. It is expensive and time-consuming to identify miRNA targets
      by using biological experiments. Many computational methods have been proposed to
      predict miRNA targets. However, these methods suffer from the high false positive
      rate because of the complex relationships between miRNAs and their targets. In
      this study, we develop a novel method, named miRTRS, for predicting miRNA targets
      based on a recommendation algorithm. miRTRS can predict targets for an
      isolated(new) miRNA with miRNA sequence similarity, as well as isolated(new)
      targets for a miRNA with gene sequence similarity. Furthermore, comparing to
      supervised machine learning methods, miRTRS does not need to select negative
      samples. We use ten-fold cross validation and independent datasets to evaluate
      the performance of our method. The experimental results have shown that our
      method miRTRS outperforms other miRNA target prediction methods in terms of AUC
      and other evaluation metrics.

PMID- 30281479
TI  - Haptic Assistance Improves Tele-manipulation With Two Asymmetric Slaves.
AB  - Tele-manipulation of heavy loads typically requires the simultaneous use of two
      asymmetric slaves: a crane for vertical weight support; and a robot for accurate
      lateral positioning. The industrial standard prescribes a pair of operators for
      such tasks (one operator to control each slave), although in principle one
      operator might control both slaves with a single, hybrid interface. Accurate and
      safe co-operative handling of the expensive and fragile heavy components is
      difficult, presumably due to problems in the coordination of the subtasks and the
      lack of mutual awareness between the two operators. This study proposes a novel
      haptic assistance system to improve subtask coordination and task performance.
      Its novelty consists of haptically linking operators/interfaces through the joint
      task environment. The system's efficacy is evaluated with fifteen pairs of co
      operators and fifteen individual uni-manual operators who manoeuvred a heavy load
      through a bounded path in Virtual Reality. Haptic assistance improves task
      completion time for both groups. It also reduces control activity and self
      reported workload without affecting a number of critical errors made by the
      operators. Moreover, without haptic assistance, uni-manual operators perform
      worse than co-operators, but this difference between the interfaces disappears
      with haptic assistance.

PMID- 30281480
TI  - Evaluation of Skin Deformation Tactile Feedback for Teleoperated Surgical Tasks.
AB  - During interaction with objects using a tool, we experience force and tactile
      feedback. One form of tactile feedback is local fingerpad skin deformation. In
      this paper, we provide haptic feedback to users of a teleoperation system through
      a skin deformation tactile feedback device. The device is able to provide
      tangential and normal skin deformation in a coupled manner, and is designed so
      that users can grasp it with a precision grip using multiple fingerpads. By
      applying skin deformation feedback on multiple fingerpads, the device is able to
      provide multi-degree-of-freedom interaction force direction and magnitude
      information to the user. To evaluate the effectiveness of this approach for the
      performance of teleoperated manipulation tasks, we performed a study in which 20
      participants used a teleoperation system to perform one of two manipulation tasks
      (peg transfer and tube connection) using force feedback, skin deformation
      feedback, and the combination of both feedback. Results showed that participants
      are able to use all feedback to improve task performance compared to the case
      without haptic feedback, although the degree of improvement depended on the
      nature of the task. The feedback also improved situation awareness, felt
      consistent with prior experience, and did not affect concentration on the task,
      as reported by participants.

PMID- 30281481
TI  - Output-Feedback Adaptive Neural Controller for Uncertain Pure-Feedback Nonlinear
      Systems Using a High-Order Sliding Mode Observer.
AB  - A novel adaptive neural output-feedback controller for SISO nonaffine pure
      feedback nonlinear systems is proposed. The majority of the previously described
      adaptive neural controllers for pure-feedback nonlinear systems were based on the
      dynamic surface control (DSC) or backstepping schemes. This makes the control law
      as well as the stability analysis highly lengthy and complicated. Moreover, there
      has been very limited research till date on the output-feedback neural controller
      for this class of the systems. The proposed controller evades adopting adaptive
      backstepping or DSC scheme through reformulating the original system into the
      Brunovsky form, which considerably simplifies the control law. Combining a high
      order sliding mode observer and single radial-basis function network with
      universal approximation property, it is shown that the controller guarantees
      closed-loop system stability in the Lyapunov sense.

PMID- 30281482
TI  - Pool-Based Sequential Active Learning for Regression.
AB  - Active learning (AL) is a machine-learning approach for reducing the data
      labeling effort. Given a pool of unlabeled samples, it tries to select the most
      useful ones to label so that a model built from them can achieve the best
      possible performance. This paper focuses on pool-based sequential AL for
      regression (ALR). We first propose three essential criteria that an ALR approach
      should consider in selecting the most useful unlabeled samples: informativeness,
      representativeness, and diversity, and compare four existing ALR approaches
      against them. We then propose a new ALR approach using passive sampling, which
      considers both the representativeness and the diversity in both the
      initialization and subsequent iterations. Remarkably, this approach can also be
      integrated with other existing ALR approaches in the literature to further
      improve the performance. Extensive experiments on 11 University of California,
      Irvine, Carnegie Mellon University StatLib, and University of Florida Media Core
      data sets from various domains verified the effectiveness of our proposed ALR
      approaches.

PMID- 30281483
TI  - Feature Analysis of Marginalized Stacked Denoising Autoenconder for Unsupervised
      Domain Adaptation.
AB  - Marginalized stacked denoising autoencoder (mSDA), has recently emerged with
      demonstrated effectiveness in domain adaptation. In this paper, we investigate
      the rationale for why mSDA benefits domain adaptation tasks from the perspective
      of adaptive regularization. Our investigations focus on two types of feature
      corruption noise: Gaussian noise (mSDAg) and Bernoulli dropout noise (mSDAbd).
      Both theoretical and empirical results demonstrate that mSDAbd successfully
      boosts the adaptation performance but mSDAg fails to do so. We then propose a new
      mSDA with data-dependent multinomial dropout noise (mSDAmd) that overcomes the
      limitations of mSDAbd and further improves the adaptation performance. Our mSDAmd
      is based on a more realistic assumption: different features are correlated and,
      thus, should be corrupted with different probabilities. Experimental results
      demonstrate the superiority of mSDAmd to mSDAbd on the adaptation performance and
      the convergence speed. Finally, we propose a deep transferable feature coding
      (DTFC) framework for unsupervised domain adaptation. The motivation of DTFC is
      that mSDA fails to consider the distribution discrepancy across different domains
      in the feature learning process. We introduce a new element to mSDA: domain
      divergence minimization by maximum mean discrepancy. This element is essential
      for domain adaptation as it ensures the extracted deep features to have a small
      distribution discrepancy. The effectiveness of DTFC is verified by extensive
      experiments on three benchmark data sets for both Bernoulli dropout noise and
      multinomial dropout noise.

PMID- 30281484
TI  - On the Representational Power of Restricted Boltzmann Machines for Symmetric
      Functions and Boolean Functions.
AB  - Restricted Boltzmann machines (RBMs) are used to build deep-belief networks that
      are widely thought to be one of the first effective deep learning neural
      networks. This paper studies the ability of RBMs to represent distributions over
      {0,1}^n via softplus/hardplus RBM networks. It is shown that any distribution
      whose density depends on the number of 1's in their input can be approximated
      with arbitrarily high accuracy by an RBM of size 2n+1, which improves the result
      of a previous study by reducing the size from n2 to 2n+1. A theorem for
      representing partially symmetric Boolean functions by softplus RBM networks is
      established. Accordingly, the representational power of RBMs for distributions
      whose mass represents the Boolean functions is investigated in comparison with
      that of threshold circuits and polynomial threshold functions. It is shown that a
      distribution over {0,1}^n whose mass represents a Boolean function can be
      computed with a given margin delta by an RBM of size and parameters bounded by
      polynomials in n, if and only if it can be computed by a depth-2 threshold
      circuit with size and parameters bounded by polynomials in n.

PMID- 30281485
TI  - Quantized Minimum Error Entropy Criterion.
AB  - Comparing with traditional learning criteria, such as mean square error, the
      minimum error entropy (MEE) criterion is superior in nonlinear and non-Gaussian
      signal processing and machine learning. The argument of the logarithm in Renyi's
      entropy estimator, called information potential (IP), is a popular MEE cost in
      information theoretic learning. The computational complexity of IP is, however,
      quadratic in terms of sample number due to double summation. This creates the
      computational bottlenecks, especially for large-scale data sets. To address this
      problem, in this paper, we propose an efficient quantization approach to reduce
      the computational burden of IP, which decreases the complexity from O( N2 ) to O(
      MN ) with M ll N. The new learning criterion is called the quantized MEE (QMEE).
      Some basic properties of QMEE are presented. Illustrative examples with linear-in
      parameter models are provided to verify the excellent performance of QMEE.

PMID- 30281486
TI  - Stochastic Conjugate Gradient Algorithm With Variance Reduction.
AB  - Conjugate gradient (CG) methods are a class of important methods for solving
      linear equations and nonlinear optimization problems. In this paper, we propose a
      new stochastic CG algorithm with variance reduction and we prove its linear
      convergence with the Fletcher and Reeves method for strongly convex and smooth
      functions. We experimentally demonstrate that the CG with variance reduction
      algorithm converges faster than its counterparts for four learning models, which
      may be convex, nonconvex or nonsmooth. In addition, its area under the curve
      performance on six large-scale data sets is comparable to that of the LIBLINEAR
      solver for the L2-regularized L2-loss but with a significant improvement in
      computational efficiency.

PMID- 30281487
TI  - Hierarchical Feature Selection for Random Projection.
AB  - Random projection is a popular machine learning algorithm, which can be
      implemented by neural networks and trained in a very efficient manner. However,
      the number of features should be large enough when applied to a rather large
      scale data set, which results in slow speed in testing procedure and more storage
      space under some circumstances. Furthermore, some of the features are redundant
      and even noisy since they are randomly generated, so the performance may be
      affected by these features. To remedy these problems, an effective feature
      selection method is introduced to select useful features hierarchically.
      Specifically, a novel criterion is proposed to select useful neurons for neural
      networks, which establishes a new way for network architecture design. The
      testing time and accuracy of the proposed method are improved compared with
      traditional methods and some variations on both classification and regression
      tasks. Extensive experiments confirm the effectiveness of the proposed method.

PMID- 30281488
TI  - Generalized Uncorrelated Regression with Adaptive Graph for Unsupervised Feature
      Selection.
AB  - Unsupervised feature selection always occupies a key position as a preprocessing
      in the tasks of classification or clustering due to the existence of extra
      essential features within high-dimensional data. Although lots of efforts have
      been made, the existing methods neglect to consider the redundancy of features,
      and thus select redundant features. In this brief, by virtue of a generalized
      uncorrelated constraint, we present an improved sparse regression model
      [generalized uncorrelated regression model (GURM)] for seeking the uncorrelated
      yet discriminative features. Benefited from this, the structure of data is kept
      in the Stiefel manifold, which avoids the potential trivial solution triggered by
      a conventional ridge regression model. Besides that, the uncorrelated constraint
      equips the model with the closed-form solution. In addition, we also incorporate
      a graph regularization term based on the principle of maximum entropy into the
      GURM model (URAFS), so as to embed the local geometric structure of data into the
      manifold learning. An efficient algorithm is designed to perform URAFS by virtue
      of the existing generalized powered iteration method. Extensive experiments on
      eight benchmark data sets among seven state-of-the-art methods on the task of
      clustering are conducted to verify the effectiveness and superiority of the
      proposed method.

PMID- 30281489
TI  - Heterogeneous Domain Adaptation Through Progressive Alignment.
AB  - In real-world transfer learning tasks, especially in cross-modal applications,
      the source domain and the target domain often have different features and
      distributions, which are well known as the heterogeneous domain adaptation (HDA)
      problem. Yet, existing HDA methods focus on either alleviating the feature
      discrepancy or mitigating the distribution divergence due to the challenges of
      HDA. In fact, optimizing one of them can reinforce the other. In this paper, we
      propose a novel HDA method that can optimize both feature discrepancy and
      distribution divergence in a unified objective function. Specifically, we present
      progressive alignment, which first learns a new transferable feature space by
      dictionary-sharing coding, and then aligns the distribution gaps on the new
      space. Different from previous HDA methods that are limited to specific
      scenarios, our approach can handle diverse features with arbitrary dimensions.
      Extensive experiments on various transfer learning tasks, such as image
      classification, text categorization, and text-to-image recognition, verify the
      superiority of our method against several state-of-the-art approaches.

PMID- 30281490
TI  - Bounded Neural Network Control for Target Tracking of Underactuated Autonomous
      Surface Vehicles in the Presence of Uncertain Target Dynamics.
AB  - This paper is concerned with the target tracking of underactuated autonomous
      surface vehicles with unknown dynamics and limited control torques. The velocity
      of the target is unknown, and only the measurements of line-of-sight range and
      angle are obtained. First, a kinematic control law is designed based on an
      extended state observer, which is utilized to estimate the uncertain target
      dynamics due to the unknown velocities. Next, an estimation model based on a
      single-hidden-layer neural network is developed to approximate the unknown
      follower dynamics induced by uncertain model parameters, unmodeled dynamics, and
      environmental disturbances. A bounded control law is designed based on the neural
      estimation model and a saturated function. The salient feature of the proposed
      controller is twofold. First, only the measured line-of-sight range and angle are
      used, and the velocity information of the target is not required. Second, the
      control torques are bounded with the bounds known as a priori. The input-to-state
      stability of the closed-loop system is analyzed via cascade theory. Simulations
      illustrate the effectiveness of the proposed bounded controller for tracking a
      moving target.

PMID- 30281491
TI  - Generalization and Expressivity for Deep Nets.
AB  - Along with the rapid development of deep learning in practice, theoretical
      explanations for its success become urgent. Generalization and expressivity are
      two widely used measurements to quantify theoretical behaviors of deep nets. The
      expressivity focuses on finding functions expressible by deep nets but cannot be
      approximated by shallow nets with similar number of neurons. It usually implies
      the large capacity. The generalization aims at deriving fast learning rate for
      deep nets. It usually requires small capacity to reduce the variance. Different
      from previous studies on deep nets, pursuing either expressivity or
      generalization, we consider both the factors to explore theoretical advantages of
      deep nets. For this purpose, we construct a deep net with two hidden layers
      possessing excellent expressivity in terms of localized and sparse approximation.
      Then, utilizing the well known covering number to measure the capacity, we find
      that deep nets possess excellent expressive power (measured by localized and
      sparse approximation) without essentially enlarging the capacity of shallow nets.
      As a consequence, we derive near-optimal learning rates for implementing
      empirical risk minimization on deep nets. These results theoretically exhibit
      advantages of deep nets from the learning theory viewpoint.

PMID- 30281492
TI  - Bag-Level Aggregation for Multiple-Instance Active Learning in Instance
      Classification Problems.
AB  - A growing number of applications, e.g., video surveillance and medical image
      analysis, require training recognition systems from large amounts of weakly
      annotated data, while some targeted interactions with a domain expert are allowed
      to improve the training process. In such cases, active learning (AL) can reduce
      labeling costs for training a classifier by querying the expert to provide the
      labels of most informative instances. This paper focuses on AL methods for
      instance classification problems in multiple instance learning (MIL), where data
      are arranged into sets, called bags, which are weakly labeled. Most AL methods
      focus on single-instance learning problems. These methods are not suitable for
      MIL problems because they cannot account for the bag structure of data. In this
      paper, new methods for bag-level aggregation of instance informativeness are
      proposed for multiple instance AL (MIAL). The aggregated informativeness method
      identifies the most informative instances based on classifier uncertainty and
      queries bags incorporating the most information. The other proposed method,
      called cluster-based aggregative sampling, clusters data hierarchically in the
      instance space. The informativeness of instances is assessed by considering bag
      labels, inferred instance labels, and the proportion of labels that remain to be
      discovered in clusters. Both proposed methods significantly outperform reference
      methods in extensive experiments using benchmark data from several application
      domains. Results indicate that using an appropriate strategy to address MIAL
      problems yields a significant reduction in the number of queries needed to
      achieve the same level of performance as single-instance AL methods.

PMID- 30281493
TI  - Temporal Attention-Augmented Bilinear Network for Financial Time-Series Data
      Analysis.
AB  - Financial time-series forecasting has long been a challenging problem because of
      the inherently noisy and stochastic nature of the market. In the high-frequency
      trading, forecasting for trading purposes is even a more challenging task, since
      an automated inference system is required to be both accurate and fast. In this
      paper, we propose a neural network layer architecture that incorporates the idea
      of bilinear projection as well as an attention mechanism that enables the layer
      to detect and focus on crucial temporal information. The resulting network is
      highly interpretable, given its ability to highlight the importance and
      contribution of each temporal instance, thus allowing further analysis on the
      time instances of interest. Our experiments in a large-scale limit order book
      data set show that a two-hidden-layer network utilizing our proposed layer
      outperforms by a large margin all existing state-of-the-art results coming from
      much deeper architectures while requiring far fewer computations.

PMID- 30281494
TI  - Multiobjective Support Vector Machines: Handling Class Imbalance With Pareto
      Optimality.
AB  - Support vector machines (SVMs) seek to optimize three distinct objectives:
      maximization of margin, minimization of regularization from the positive class,
      and minimization of regularization from the negative class. The right choice of
      weightage for each of these objectives is critical to the quality of the
      classifier learned, especially in case of the class imbalanced data sets.
      Therefore, costly parameter tuning has to be undertaken to find a set of suitable
      relative weights. In this brief, we propose to train SVMs, on two-class as well
      as multiclass data sets, in a multiobjective optimization framework called radial
      boundary intersection to overcome this shortcoming. The experimental results
      suggest that the radial boundary intersection-based scheme is indeed effective in
      finding the best tradeoff among the objectives compared with parameter-tuning
      schemes.

PMID- 30281495
TI  - Face Sketch Synthesis by Multidomain Adversarial Learning.
AB  - Given a training set of face photo-sketch pairs, face sketch synthesis targets at
      learning a mapping from the photo domain to the sketch domain. Despite the
      exciting progresses made in the literature, it retains as an open problem to
      synthesize high-quality sketches against blurs and deformations. Recent advances
      in generative adversarial training provide a new insight into face sketch
      synthesis, from which perspective the existing synthesis pipelines can be
      fundamentally revisited. In this paper, we present a novel face sketch synthesis
      method by multidomain adversarial learning (termed MDAL), which overcomes the
      defects of blurs and deformations toward high-quality synthesis. The principle of
      our scheme relies on the concept of ''interpretation through synthesis.'' In
      particular, we first interpret face photographs in the photodomain and face
      sketches in the sketch domain by reconstructing themselves respectively via
      adversarial learning. We define the intermediate products in the reconstruction
      process as latent variables, which form a latent domain. Second, via adversarial
      learning, we make the distributions of latent variables being indistinguishable
      between the reconstruction process of the face photograph and that of the face
      sketch. Finally, given an input face photograph, the latent variable obtained by
      reconstructing this face photograph is applied for synthesizing the corresponding
      sketch. Quantitative comparisons to the state-of-the-art methods demonstrate the
      superiority of the proposed MDAL method.

PMID- 30281496
TI  - Deep Semantic-Preserving Ordinal Hashing for Cross-Modal Similarity Search.
AB  - Cross-modal hashing has attracted increasing research attention due to its
      efficiency for large-scale multimedia retrieval. With simultaneous feature
      representation and hash function learning, deep cross-modal hashing (DCMH)
      methods have shown superior performance. However, most existing methods on DCMH
      adopt binary quantization functions (e.g., sign(.)) to generate hash codes, which
      limit the retrieval performance since binary quantization functions are sensitive
      to the variations of numeric values. Toward this end, we propose a novel end-to
      end ranking-based hashing framework, in this paper, termed as deep semantic
      preserving ordinal hashing (DSPOH), to learn hash functions with deep neural
      networks by exploring the ranking structure of feature dimensions. In DSPOH, the
      ordinal representation, which encodes the relative rank ordering of feature
      dimensions, is explored to generate hash codes. Such ordinal embedding benefits
      from the numeric stability of rank correlation measures. To make the hash codes
      discriminative, the ordinal representation is expected to well predict the class
      labels so that the ranking-based hash function learning is optimally compatible
      with the label predicting. Meanwhile, the intermodality similarity is preserved
      to guarantee that the hash codes of different modalities are consistent.
      Importantly, DSPOH can be effectively integrated with different types of network
      architectures, which demonstrates the flexibility and scalability of our proposed
      hashing framework. Extensive experiments on three widely used multimodal data
      sets show that DSPOH outperforms state of the art for cross-modal retrieval
      tasks.

PMID- 30281497
TI  - Distributed Adaptive Tracking Synchronization for Coupled Reaction-Diffusion
      Neural Network.
AB  - This paper considers the tracking synchronization problem for a class of coupled
      reaction-diffusion neural networks (CRDNNs) with undirected topology. For the
      case where the tracking trajectory has identical individual dynamic as that of
      the network nodes, the edge-based and vertex-based adaptive strategies on
      coupling strengths as well as adaptive controllers, which demand merely the local
      neighbor information, are proposed to synchronize the CRDNNs to the tracking
      trajectory. To reduce the control costs, an adaptive pinning control technique is
      employed. For the case where the tracking trajectory has different individual
      dynamic from that of the network nodes, the vertex-based adaptive strategy is
      proposed to drive the synchronization error to a relatively small area, which is
      adjustable according to the parameters of the adaptive strategy. This kind of
      adaptive design can enhance the robustness of the network against the external
      disturbance posed on the tracking trajectory. The obtained theoretical results
      are verified by two representative examples.

PMID- 30281498
TI  - Deep Neural Network Initialization With Decision Trees.
AB  - In this paper, a novel, automated process for constructing and initializing deep
      feedforward neural networks based on decision trees is presented. The proposed
      algorithm maps a collection of decision trees trained on the data into a
      collection of initialized neural networks with the structures of the networks
      determined by the structures of the trees. The tree-informed initialization acts
      as a warm-start to the neural network training process, resulting in efficiently
      trained, accurate networks. These models, referred to as ''deep jointly informed
      neural networks'' (DJINN), demonstrate high predictive performance for a variety
      of regression and classification data sets and display comparable performance to
      Bayesian hyperparameter optimization at a lower computational cost. By combining
      the user-friendly features of decision tree models with the flexibility and
      scalability of deep neural networks, DJINN is an attractive algorithm for
      training predictive models on a wide range of complex data sets.

PMID- 30281499
TI  - Nonuniformly Sampled Data Processing Using LSTM Networks.
AB  - We investigate classification and regression for nonuniformly sampled variable
      length sequential data and introduce a novel long short-term memory (LSTM)
      architecture. In particular, we extend the classical LSTM network with additional
      time gates, which incorporate the time information as a nonlinear scaling factor
      on the conventional gates. We also provide forward-pass and backward-pass update
      equations for the proposed LSTM architecture. We show that our approach is
      superior to the classical LSTM architecture when there is correlation between
      time samples. In our experiments, we achieve significant performance gains with
      respect to the classical LSTM and phased-LSTM architectures. In this sense, the
      proposed LSTM architecture is highly appealing for the applications involving
      nonuniformly sampled sequential data.

PMID- 30281500
TI  - Neuroimaging Retrieval via Adaptive Ensemble Manifold Learning for Brain Disease
      Diagnosis.
AB  - Alzheimer's disease (AD) is a neurodegenerative and non-curable disease, with
      serious cognitive impairment, such as dementia. Clinically, it is critical to
      study the disease with multi-source data in order to capture a global picture of
      it. In this respect, an adaptive ensemble manifold learning (AEML) algorithm is
      proposed to retrieve multi-source neuroimaging data. Specifically, an objective
      function based on manifold learning is formulated to impose geometrical
      constraints by similarity learning. The complementary characteristics of various
      sources of brain disease data for disorder discovery are investigated by tuning
      weights from ensemble learning. In addition, a generalized norm is explicitly
      explored for adaptive sparseness degree control. The proposed AEML algorithm is
      evaluated by the public Alzheimer's disease neuroimaging initiative (ADNI)
      database. Results obtained from the extensive experiments demonstrate that our
      algorithm outperforms the traditional methods.

PMID- 30281501
TI  - Simultaneous Volumetric Segmentation of Vertebral Bodies and Intervertebral Discs
      on Fat-Water MR Images.
AB  - Fat-water magnetic resonance (MR) images allow automated noninvasive analysis of
      morphological properties and fat fractions of vertebral bodies (VBs) and
      intervertebral discs (IVDs) that constitute an important part of human
      biomechanical systems. In this paper, we propose a fully automated approach for
      simultaneously segmenting multiple VBs and IVDs on fat-water MR images without
      prior localization or geometry estimation. This method involved a hierarchical
      random forest (HRF) classifier and a hierarchical conditional random field (HCRF)
      that encoded amulti-resolution image pyramid based on a set of multiscale local
      and contextual features. The HRF classifier employed penalized multivariate
      linear discriminants and SMOTEBagging to handle limited and imbalanced training
      data with large feature dimension. The HCRF estimated optimum labels according to
      their spatial and hierarchical consistencies by using the layer-wise significant
      features determined over the trained HRF classifier. To handle variable sample
      numbers at different resolutions, resolutionspecific hyperparameters were used.
      This method was trained and evaluated for segmenting 15 thoracic and lumbar VBs
      and their IVDs on fat-water MR images of a subset of a large cohort data set. It
      was further evaluated for segmenting 7 IVDs of the lower spine on fat-water
      images of a public grand challenge. These evaluations revealed the comparable
      accuracy of this method with the state-ofthe-art while requiring less
      computational burden due to a simultaneous localization and segmentation.

PMID- 30281502
TI  - A hybrid feature selection method based on binary state transition algorithm and
      ReliefF.
AB  - Feature selection problems often appear in the application of data mining, which
      have been difficult to handle due to the NP-hard property of these problems. In
      this study, a simple but efficient hybrid feature selection method is proposed
      based on binary state transition algorithm (BSTA) and ReliefF, called ReliefF
      BSTA. This method contains two phases: the filter phase and the wrapper phase.
      There are three aspects of advantages in this method. First, an initialization
      approach based on feature ranking is designed to make sure that the initial
      solution is not easy to get tapped into local optimum. Then a probability
      substitute operator based on feature weights is developed to update the current
      solution according to the different mutation probabilities of the features.
      Finally, a new selection strategy based on relative dominance is presented to
      find the current best solution. The simple and efficient algorithm -Nearest
      Neighborhood (-NN) with the leave-one-out cross validation is used as a
      classifier to evaluate feature subset candidates. The experimental results
      indicate that the proposed method is more efficient in terms of the
      classification accuracy through a comparison to other feature selection methods
      using seven public datasets and several real biomedical datasets. For public
      datasets, the proposed method improved the classification average accuracy by
      about 2.5% compared with the filter method. For a specific biomedical dataset
      AID1284, the classification accuracy significantly increased from 77.24% to
      85.25% by using the proposed method.

PMID- 30281503
TI  - A Three-stage Deep Learning Model for Accurate Retinal Vessel Segmentation.
AB  - Automatic retinal vessel segmentation is a fundamental step in the diagnosis of
      eye-related diseases, in which both thick vessels and thin vessels are important
      features for symptom detection. All existing deep learning models attempt to
      segment both types of vessels simultaneously by using a unified pixelwise loss
      which treats all vessel pixels with equal importance. Due to the highly
      imbalanced ratio between thick vessels and thin vessels (namely the majority of
      vessel pixels belong to thick vessels), the pixel-wise loss would be dominantly
      guided by thick vessels and relatively little influence comes from thin vessels,
      often leading to low segmentation accuracy for thin vessels. To address the
      imbalance problem, in this paper, we explore to segment thick vessels and thin
      vessels separately by proposing a three-stage deep learning model. The vessel
      segmentation task is divided into three stages, namely thick vessel segmentation,
      thin vessel segmentation and vessel fusion. As better discriminative features
      could be learned for separate segmentation of thick vessels and thin vessels,
      this process minimizes the negative influence caused by their highly imbalanced
      ratio. The final vessel fusion stage refines the results by further identifying
      non-vessel pixels and improving the overall vessel thickness consistency. The
      experiments on public datasets DRIVE, STARE and CHASE DB1 clearly demonstrate
      that the proposed threestage deep learning model outperforms the current state-of
      theart vessel segmentation methods.

PMID- 30281504
TI  - Kinematic and Kinetic Validation of an Improved Depth Camera Motion Assessment
      System Using Rigid Bodies.
AB  - The study of joint kinematics and dynamics has broad clinical applications
      including the identification of pathological motions or compensation strategies
      and the analysis of dynamic stability. High-end motion capture systems, however,
      are expensive and require dedicated camera spaces with lengthy set-up and data
      processing commitments. Depth cameras, such as the Microsoft Kinect, provide an
      inexpensive, marker-free alternative at the sacrifice of joint-position accuracy.
      In this work, we present a fast framework for adding biomechanical constraints to
      the joint estimates provided by a depth camera system. We also present a new
      model for the lower lumbar joint angle. We validate key joint position, angle,
      and velocity measurements against a gold standard active motion-capture system on
      ten healthy subjects performing sit-to-stand (STS). Our method showed significant
      improvement in Mean Absolute Error and Intraclass Correlation Coefficients for
      the recovered joint angles and position-based metrics. These improvements suggest
      that depth cameras can provide an accurate and clinically viable method of
      rapidly assessing the kinematics and kinetics of the STS action, providing data
      for further analysis using biomechanical or machine learning methods.

PMID- 30281505
TI  - Distributed Hinfinity Estimation in Sensor Networks With Two-Channel Stochastic
      Attacks.
AB  - This paper is concerned with the distributed estimation problem in sensor
      networks subjected to unknown attacks. Network attacks are considered to exist in
      two classes of channels: 1) communication channels from the plant to sensors and
      2) communication channels among sensors. The status of an attack is viewed as a
      stochastic phenomenon, and the transmitted information will be affected when the
      attacker successfully carries out an attack on the related data packet. Based on
      the sensors' own measurements and their neighbors' local information, a novel
      distributed estimation model against two-channel stochastic attacks is presented.
      A sufficient condition on the existence of the desired distributed Hinfinity
      estimators is derived and the distributed estimator gains are designed by solving
      a linear matrix inequality. Two illustrative examples are provided to demonstrate
      the effectiveness of the new design techniques.

PMID- 30281506
TI  - Visual Tracking and Depth Estimation of Mobile Robots Without Desired Velocity
      Information.
AB  - In this paper, a visual servoing approach is developed for the trajectory
      tracking control and depth estimation problem of a mobile robot without a priori
      knowledge about desired velocities. By exploiting the multiple images captured by
      the on-board camera, the current and desired poses (i.e., scaled translation and
      orientation) of the mobile robot are reconstructed to define system errors. Then,
      an adaptive time-varying controller is proposed to achieve the trajectory
      tracking task in the presence of nonholonomic constraint and unknown depth
      parameters. Most of previous works require the measurement of the desired
      velocity information to facilitate the controller design, leading to tedious
      offline computation. In this paper, to eliminate this requirement, the desired
      velocities are estimated in real-time based on a reduced order observer.
      Moreover, an augmented update law is designed to compensate for the unknown depth
      parameters and identify the inverse depth constant. The Lyapunov-based method is
      employed to prove that the proposed controller achieves asymptotic tracking, and
      the inverse depth estimate converges to its actual value provided that a
      persistent excitation condition is satisfied. Subsequently, a robust data-driven
      algorithm is introduced to ensure the convergence of the inverse depth estimate
      under a relaxed finite excitation condition. Simulation and experimental results
      are provided to demonstrate the effectiveness of the proposed approach.

PMID- 30281507
TI  - R$2$BN: An Adaptive Model for Keystroke-Dynamics-Based Educational Level
      Classification.
AB  - Over the past decade, keystroke-based pattern recognition techniques, as a
      forensic tool for behavioral biometrics, have gained increasing attention.
      Although a number of machine learning-based approaches have been proposed, they
      are limited in terms of their capability to recognize and profile a set of an
      individual's characteristics. In addition, up to today, their focus was primarily
      gender and age, which seem to be more appropriate for commercial applications
      (such as developing commercial software), leaving out from research other
      characteristics, such as the educational level. Educational level is an acquired
      user characteristic, which can improve targeted advertising, as well as provide
      valuable information in a digital forensic investigation, when it is known. In
      this context, this paper proposes a novel machine learning model, the randomized
      radial basis function network, which recognizes and profiles the educational
      level of an individual who stands behind the keyboard. The performance of the
      proposed model is evaluated by using the empirical data obtained by recording
      volunteers' keystrokes during their daily usage of a computer. Its performance is
      also compared with other well-referenced machine learning models using our
      keystroke dynamic datasets. Although the proposed model achieves high accuracy in
      educational level prediction of an unknown user, it suffers from high
      computational cost. For this reason, we examine ways to reduce the time that is
      needed to build our model, including the use of a novel data condensation method,
      and discuss the tradeoff between an accurate and a fast prediction. To the best
      of our knowledge, this is the first model in the literature that predicts the
      educational level of an individual based on the keystroke dynamics information
      only.

PMID- 30281508
TI  - Hyper-Laplacian Regularized Multilinear Multiview Self-Representations for
      Clustering and Semisupervised Learning.
AB  - In this paper, we address the multiview nonlinear subspace representation
      problem. Traditional multiview subspace learning methods assume that the
      heterogeneous features of the data usually lie within the union of multiple
      linear subspaces. However, instead of linear subspaces, the data feature actually
      resides in multiple nonlinear subspaces in many real-world applications,
      resulting in unsatisfactory clustering performance. To overcome this, we propose
      a hyper-Laplacian regularized multilinear multiview self-representation model,
      which is referred to as HLR-M2VS, to jointly learn multiple views correlation and
      a local geometrical structure in a unified tensor space and view-specific self
      representation feature spaces, respectively. In unified tensor space, a well
      founded tensor low-rank regularization is adopted to impose on the self
      representation coefficient tensor to ensure global consensus among different
      views. In view-specific feature space, hypergraph-induced hyper-Laplacian
      regularization is utilized to preserve the local geometrical structure embedded
      in a high-dimensional ambient space. An efficient algorithm is then derived to
      solve the optimization problem of the established model with theoretical
      convergence guarantee. Furthermore, the proposed model can be extended to
      semisupervised classification without introducing any additional parameters. An
      extensive experiment of our method is conducted on many challenging datasets,
      where a clear advance over state-of-the-art multiview clustering and multiview
      semisupervised classification approaches is achieved.

PMID- 30281509
TI  - Automatic Tuning of the RBF Kernel Parameter for Batch-Mode Active Learning
      Algorithms: A Scalable Framework.
AB  - Batch-mode active learning algorithms can select a batch of valuable unlabeled
      samples to manually annotate for reducing the total cost of labeling every
      unlabeled sample. To facilitate selection of valuable unlabeled samples, many
      batch-mode active learning algorithms map samples to the reproducing kernel
      Hilbert space induced by a radial-basis function (RBF) kernel. Setting a proper
      value to the parameter for the RBF kernel is crucial for such batch-mode active
      learning algorithms. In this paper, for automatic tuning of the kernel parameter,
      a hypothesis-margin-based criterion function is proposed. Three frameworks are
      also developed to incorporate the function of automatic tuning of the kernel
      parameter with existing batch-model active learning algorithms. In the proposed
      frameworks, the kernel parameter can be tuned in a single stage or in multiple
      stages. Tuning the kernel parameter in a single stage aims for the kernel
      parameter to be suitable for selecting the specified number of unlabeled samples.
      When the kernel parameter is tuned in multiple stages, the incorporated active
      learning algorithm can be enforced to make coarse-to-fine evaluations of the
      importance of unlabeled samples. The proposed framework can also improve the
      scalability of existing batch-mode active learning algorithms satisfying a
      decomposition property. Experimental results on data sets comprising hundreds to
      hundreds of thousands of samples have shown the feasibility of the proposed
      framework.

PMID- 30281510
TI  - Adaptive Fuzzy Control of Stochastic Nonlinear Systems With Fuzzy Dead Zones and
      Unmodeled Dynamics.
AB  - This paper focuses on an input-to-state practical stability problem for a class
      of stochastic nonlinear systems with unmodeled dynamics and fuzzy dead zones. A
      feasible adaptive fuzzy control method is proposed for the developed stochastic
      system with the slope of dead zone being certain or fuzzy. Based on stochastic
      small-gain theorem and backstepping technique, the closed-loop system is
      guaranteed to be input-state-practically stable in probability. The main
      contributions of this paper lie in that the considered system is more general,
      and the modified Lemma 2 makes the presentation of the formulas in lemma
      consistent with their application forms. Finally, two simulation examples are
      provided to demonstrate the effectiveness of the proposed approach.

PMID- 30281511
TI  - Mitochondria-Driven Elimination of Cancer and Senescent Cells.
AB  - Mitochondria and oxidative phosphorylation (OXPHOS) are emerging as intriguing
      targets for efficient elimination of cancer cells. The specificity of this
      approach is aided by the capacity of non-proliferating non-cancerous cells to
      withstand oxidative insult induced by OXPHOS inhibition. Recently we discovered
      that mitochondrial targeting can also be employed to eliminate senescent cells,
      where it breaks the interplay between OXPHOS and ATP transporters that appear
      important for the maintenance of mitochondrial morphology and viability in the
      senescent setting. Hence, mitochondria/OXPHOS directed pharmacological
      interventions show promise in several clinically-relevant scenarios that call for
      selective removal of cancer and senescent cells.

PMID- 30281512
TI  - The frequency of testing for glycated haemoglobin, HbA1c, is linked to the
      probability of achieving target levels in patients with suboptimally controlled
      diabetes mellitus.
AB  - Background We previously showed, in patients with diabetes, that >50% of
      monitoring tests for glycated haemoglobin (HbA1c) are outside recommended
      intervals and that this is linked to diabetes control. Here, we examined the
      effect of tests/year on achievement of commonly utilised HbA1c targets and on
      HbA1c changes over time. Methods Data on 20,690 adults with diabetes with a
      baseline HbA1c of >53 mmol/mol (7%) were extracted from Clinical Biochemistry
      Laboratory records at three UK hospitals. We examined the effect of HbA1c
      tests/year on (i) the probability of achieving targets of <=53 mmol/mol (7%) and
      <=48 mmol/mol (6.5%) in a year using multi-state modelling and (ii) the changes
      in mean HbA1c using a linear mixed-effects model. Results The probabilities of
      achieving <=53 mmol/mol (7%) and <=48 mmol/mol (6.5%) targets within 1 year were
      0.20 (95% confidence interval: 0.19-0.21) and 0.10 (0.09-0.10), respectively.
      Compared with four tests/year, having one test or more than four tests/year were
      associated with lower likelihoods of achieving either target; two to three
      tests/year gave similar likelihoods to four tests/year. Mean HbA1c levels were
      higher in patients who had one test/year compared to those with four tests/year
      (mean difference: 2.64 mmol/mol [0.24%], p<0.001). Conclusions We showed that
      >=80% of patients with suboptimal control are not achieving commonly recommended
      HbA1c targets within 1 year, highlighting the major challenge facing healthcare
      services. We also demonstrated that, although appropriate monitoring frequency is
      important, testing every 6 months is as effective as quarterly testing,
      supporting international recommendations. We suggest that the importance HbA1c
      monitoring frequency is being insufficiently recognised in diabetes management.

PMID- 30281513
TI  - "Decide Now, Buy Marlboro": Examining the influence and appeal of Marlboro's new
      brand architecture among Filipino adolescents.
AB  - In recent years, Philip Morris International (PMI) launched a global rebranding
      strategy to expand the reach of Marlboro. Using a mixed-methods design, this
      study evaluated the appeal and influence of Marlboro advertising among Filipino
      youth. Six hundred and twenty-three adolescents aged 13-17 years old in Metro
      Manila participated in a survey, including three advertising conditions: two for
      Marlboro and one for Mighty, a local cigarette brand. One-way repeated measures
      analysis of variance (ANOVA) and paired t-tests evaluated differences between the
      three conditions on participants' attitudes toward advertisements [measured as
      identification, likeability, and perceived effectiveness (PE)]. Compared to
      Mighty, never-smokers rated Marlboro advertisements as more identifiable and
      likeable. Comparing by smoking status (never vs. ever), multivariable logistic
      regression assessed the influence of these attitudes on intention to smoke.
      Increased likeability was associated with greater intention to smoke among never
      smokers, and greater PE increased odds of intention to smoke for both never- and
      ever-smokers. Additionally, six focus group discussions (FGD) explored responses
      to campaign messaging. Themes were compared within and across groups. Marlboro
      was also appealing to FGD participants, who described the ads as attractive to
      youth and promoting "adventure" and "freedom", whereas the Mighty brand was seen
      as being for adults and current smokers. Our findings illustrate that Marlboro
      advertisements are distinctly appealing to youth. Marlboro rhetoric - where
      consumers are urged to "decide" to "Be Marlboro" - was particularly powerful.
      These findings support the need for addressing gaps in policies regulating the
      marketing and promotion of tobacco in the Philippines.

PMID- 30281514
TI  - Review of thiamine deficiency disorders: Wernicke encephalopathy and Korsakoff
      psychosis.
AB  - Wernicke encephalopathy (WE) and Korsakoff psychosis (KP), together termed
      Wernicke-Korsakoff syndrome (WKS), are distinct yet overlapping neuropsychiatric
      disorders associated with thiamine deficiency. Thiamine pyrophosphate, the
      biologically active form of thiamine, is essential for multiple biochemical
      pathways involved in carbohydrate utilization. Both genetic susceptibilities and
      acquired deficiencies as a result of alcoholic and non-alcoholic factors are
      associated with thiamine deficiency or its impaired utilization. WKS is
      underdiagnosed because of the inconsistent clinical presentation and overlapping
      of symptoms with other neurological conditions. The identification and
      individualized treatment of WE based on the etiology is vital to prevent the
      development of the amnestic state associated with KP in genetically predisposed
      individuals. Through this review, we bring together the existing data from animal
      and human models to expound the etiopathogenesis, diagnosis, and therapeutic
      interventions for WE and KP.

PMID- 30281515
TI  - Bipolar radiofrequency neurotomy for spinal pain - a promising technique but
      still some steps to go.

PMID- 30281516
TI  - Galactosaemia - should it be screened in newborns?

PMID- 30281517
TI  - Difficulties in the dietary management of a girl with two diseases requiring a
      special diet.
AB  - 3-Methylcrotonylglycinuria (3-MCG) is an autosomal recessive inborn error of
      leucine metabolism caused by the deficiency of 3-methylocrotonyl-CoA carboxylase
      (3-MCC deficiency). It is the most commonly detected organic aciduria in newborn
      screening conducted by tandem mass spectrometry (MS/MS) [1, 2]. The clinical
      phenotype is heterogeneous, ranging from asymptomatic to acute metabolic
      decompensations [3, 4]. Although at least in severe cases and in acute life
      threatening episodes limiting natural protein intake (particularly leucine)
      together with high caloric intake during catabolic periods is required, the need
      for specific dietary management often seems questionable [2]. In contrast with
      the 3-MCC deficiency, in diabetes mellitus type 1 (DM1) a diet based on
      carbohydrate and protein-fat exchangers is beyond dispute. However, as DM1 is
      quite a common disease, it may occur in a single patient with a rare disease,
      such as 3-MCC deficiency.

PMID- 30281518
TI  - The practical significance of perinatal cardiology based on own experience.
AB  - The article underlined the role of perinatal cardiology in contributing to the
      medical care of the pregnant woman taking into consideration the technical and
      medical progress which has made it possible to save not only human life but also
      its quality. The role of correct early diagnosis, as well as correct treatment
      was discussed and the results of such procedure demonstrated.

PMID- 30281519
TI  - Factors affecting the differentiation of the Apgar score and the biochemical
      correlation of fetal well-being - a prospective observational clinical study.
AB  - OBJECTIVE: Objective: The purpose of the study was to identify the features of
      both the labor and the assisting physicians when evaluating the newborn according
      to the Apgar score and how these correlate with the biochemical markers of fetal
      well-being in order to make the Apgar score more objective. PATIENTS AND METHODS:
      Material and methods: A prospective observational clinical study conducted in a
      3rd reference level center between 1st April 2014 and 31st March 2015. The study
      enrolled 17 neonatologists and 1527 term newborns. RESULTS: Results: The Apgar
      score is highest after natural vaginal delivery, lower after instrumental labor
      (p <0.001). The pH of the umbilical cord blood and lactate concentration
      correlate better with a high score than with a lowered one. The young age of a
      physician does not reduce Apgar score reliability. There were no differences in
      Apgar assessment according to physicians' training and the time of labor. There
      were no correlations between abnormalities in postnatal central nervous system
      ultrasound and the Apgar score. CONCLUSION: Conclusion: Biochemical tests of
      umbilical cord blood significantly increase the Apgar score reliability.

PMID- 30281520
TI  - [Development in the first year of life of newborns born prematurely - preliminary
      report].
AB  - OBJECTIVE: Introduction: Premature babies account for almost 7% of all newborns
      and the number of extremely premature infants is increasing. In the European
      Parliament the problem of premature birth was identified as a priority health
      task as early as 2011. It is emphasized that the problems of a premature newborn
      do not end with discharge from hospital. Objective: The aim of the paper was a
      tentative analysis of the development level of infants born before the 37th week
      of intrauterine life, taking into account various areas of development and
      searching for differences in the levels of the development of newborns born
      prematurely and on time. PATIENTS AND METHODS: Material and methods: The research
      covered two groups of babies: group I - infants born prematurely (between the
      25th and 36th week of their intrauterine life) examined in their 11.5-12.5 month,
      group II - infants born in due time, examined in their 11.5-12.5 month.
      Evaluation was carried out in accordance with the Munich Functional Developmental
      Diagnostics. The analysis comprised 50 questionnaires of prematurely born babies
      and 30 infants born in due time. Gross and fine motor skills were assessed, as
      well as autonomy and perception. RESULTS: Results: In our general evaluation, 80%
      of the children from group I were active in accordance with their birth age.
      However, as regards the analysis of development in particular areas, 50% of the
      children from group I undertook activity compliant with their birth age. The
      analysis of average values indicates the relationship between the level of
      prematurity and the level of activity presented by the children examined. As the
      level of prematurity increases, the level of activity presented by the children
      decreases. The greatest difficulties in group I were noted with regards to
      perception and autonomy. CONCLUSION: Conclusions: The level of activity presented
      by the children born prematurely at the age of 12 months depends on their level
      of prematurity. Newborn babies who were born prematurely require diagnostics
      specifying different spheres of development.

PMID- 30281521
TI  - Infant and baby feeding and the development of the maxillofacial complex based on
      own observations and the literature.
AB  - The method and technique of feeding a young child affect the shape of the
      maxillofacial complex. Breastfeeding is the recommended method of feeding in the
      first six months of life. It is encouraged to continue natural feeding in later
      months, simultaneously developing other food extraction techniques. The correct
      formation of the stomatognathic system is a result of the correct organization of
      the motor patterns during feeding.

PMID- 30281522
TI  - Early complications of extracorporeal shockwave lithotripsy in the records of the
      Department of Paediatrics, Nephrology and Allergology of the Military Institute
      of Medicine - preliminary results.
AB  - The aim of the study was to analyse the frequency and type of early complications
      of extracorporeal shock wave lithotripsy (ESWL) and to assess the safety of the
      procedure among paediatric patients. The study is a retrospective analysis of all
      ESWL procedures carried out due to urolithiasis in 2009-2015 in the Department of
      Paediatrics, Nephrology and Allergology of the Military Institute of Medicine.
      Medical records of 170 children were analysed: 94 girls (55.3%) and 76 boys
      (44.7%) aged 1 to 18 years. Out of the 272 procedures performed, 247 were
      included in the study. Among 233 effective ESWL treatments, complications were
      noted in 35 (15.02%) procedures: among 10 girls (40%) and 15 boys (60%). In 25
      cases (10.73%) surgical intervention was necessary due to urinary obstruction
      caused by a fragment of a disintegrated stone. Urinary tract infection was
      present among 3 patients (1.29%) who required surgical treatment. Nonsurgical
      complications included 7 urinary tract infections (3%) and 3 cases of severe
      abdominal pain (1.29%). Complications such as perirenal haematoma, subcapsular
      haematoma or ureteral perforation were not observed. The vast majority of
      complications observed in the study were associated with urinary obstruction
      caused by partial blockage of the ureter with kidney stone fragments
      ("steinstrasse"). Despite the complications that were documented, ESWL should be
      considered a safe procedure.

PMID- 30281523
TI  - Pathophysiology and symptoms of renal colic in children - a case report.
AB  - Urolithiasis is a disease characterized by the presence of stones in the kidney
      or urinary tract. It is often detected accidentally during an ultrasound or an
      abdominal x-ray performed for other reasons. However, the first symptom of kidney
      stone disease can be severe pain called renal colic. Pain caused by a colic
      attack is characterized by sudden onset. In half of the cases it is associated
      with nausea or vomiting and can lead to hypotension and fainting. The exact
      location and radiation of the pain depends on the location of the stone in the
      urinary tract. The first most commonly performed study is abdominal ultrasound
      with estimation of the deposit size and evaluation of urinary tract obstruction.
      Alternative or complementary studies are: an abdominal x-ray where radiopaque
      deposits can be shown, or unenhanced helical computed tomography of the abdomen.
      The severity of pain depends on the individual pain threshold and on the change
      in hydrostatic pressure in the part of the urinary system above the obstruction.
      Prolonged deposition of the stone in one place causes the activation of
      autoregulatory mechanisms to lower the pressure of the upper urinary tract, which
      limits the pain. The basic treatment for renal colic is analgetic therapy. The
      most commonly used drugs are NSAIDs and opiates. Another important component of
      renal colic treatment are medications that facilitate urinary stone passage by
      reducing oedema or limiting urethral contractions, such as: calcium channel
      blockers, alpha blockers, phosphodiesterase inhibitors. Intensive hydration is
      not currently recommended. Patients who are unlikely to spontaneously excrete the
      stone are eligible for minimally invasive treatment. The risk of urolithiasis
      recurring is high, reaching up to 40% in 5 years and up to 50% in 10 years.
      However, it can be reduced by proper prevention. The paper describes the
      pathophysiology of pain in renal colic, the treatment methods, and the case of a
      boy with recurrent renal colic.

PMID- 30281524
TI  - The role of perinatal cardiology in saving the life and its quality of fetuses,
      newborns and children (on the basis of own experience and review of the
      literature).
AB  - The role of prenatal cardiology and the organization of perinatal cardiological
      centers in early diagnostics and early therapeutic procedures in fetuses and
      newborns with cardiac malformations and circulatory disturbances was discussed on
      the basis of the literature and own experience. The possibilities of an early
      perinatal diagnosis and early therapeutic approaches to cardiac defects were
      presented. It was stressed that there is a necessity to broaden the educational
      aims in these areas and in the near future to prepare multidisciplinary teams
      working together in specialist centers.

PMID- 30281525
TI  - Cortisol deficiency as a rare cause of neonatal cholestasis.
AB  - Cortisol deficiency constitutes a rare cause of neonatal cholestasis. The aim of
      this manuscript was to present the pathogenesis of cortisol deficiency in
      neonatal cholestasis. The authors also present the characteristics of selected
      disorders resulting in cortisol deficiency.

PMID- 30281526
TI  - Chemoradiotherapy for Unresectable INI1-negative Chordoma in a Child.
AB  - The characteristics of chordomas in children are distinct from those in adults.
      In particular, the prognosis of patients with INI1-negative chordoma is dismal.
      The standard treatment for localized chordoma, complete surgical resection with a
      wide margin, is seldom feasible for chordomas arising at the clivus in children,
      mainly due to associated complications. Therefore, other treatments for
      unresectable chordomas in children, including chemoradiotherapy, must be
      explored. Here, we report a 7-year-old girl with an INI1-negative chordoma of the
      clivus, who responded to conventional chemotherapy plus radiotherapy. Without
      surgical resection, she remains alive after 1 year and 7 months of the initial
      diagnosis.

PMID- 30281527
TI  - Ophthalmic manifestations associated with RARB mutations.

PMID- 30281528
TI  - Nonrheumatoid Fibrinous Pericarditis: A Medical Examiner Algorithm for the
      Diagnosis of Viral Myocarditis and Use of Molecular Diagnostic Techniques.
AB  - Classic "bread-and-butter" appearance of fibrinous pericarditis had been
      described in rheumatic disease and other immunologic diseases such as systemic
      lupus erythematosus, post-myocardial infarct, uremia, tuberculosis, radiation
      effects, bacterial, and viral etiology. In most of the described cases,
      pericarditis occurs as a delayed complication. We present a case of a 21-year-old
      white woman who was seen in the emergency department to rule out pulmonary
      embolism for shortness of breath, chest pain, and lightheadedness. The autopsy
      showed a collection of serous fluid into the pericardial sac with bread-and
      butter appearance. Microscopically, the pericardium showed acute inflammation
      with fibrinous exudates. Sections of the heart showed areas of lymphocytic
      infiltration with acute fibrinous inflammation of the pericardium. Vasculitis was
      seen in small blood vessels in the heart and was negative in other organs. No
      granuloma or necrotizing lesion was seen in microscopic sections of all organs
      including the heart, ruling out rheumatologic disease. The present study
      highlights the quest and design of an algorithm for a nonrheumatic disorder as
      the cause of pericarditis. Molecular studies were performed on heart tissue
      blocks for identification of cardiotropic viruses. Human parvovirus B19 was
      isolated from heart tissue blocks. The present case study highlights on updates
      in pathophysiology and diagnostic criteria for myocarditis along with the use of
      new molecular techniques for detection of idiopathic cardiomyopathies in a
      medical examiner setup.

PMID- 30281530
TI  - Index: Authors of Abstracts.

PMID- 30281529
TI  - Schedule-at-a-Glance.

PMID- 30281531
TI  - Acquisition of analgesic properties by the cholecystokinin (CCK)/CCK2 receptor
      system within the amygdala in a persistent inflammatory pain condition.
AB  - Pain is associated with negative emotions such as anxiety, but the underlying
      neurocircuitry and modulators of the association of pain and anxiety remain
      unclear. The neuropeptide cholecystokinin (CCK) has both pronociceptive and
      anxiogenic properties, so we explored the role of CCK in anxiety and nociception
      in the central amygdala (CeA), a key area in control of emotions and descending
      pain pathways. Local infusion of CCK into the CeA of control rats increased
      anxiety, as measured in the light-dark box test, but had no effect on mechanical
      sensitivity. By contrast, intra-CeA CCK infusion 4 days after Complete Freund's
      Adjuvant (CFA) injection into the hindpaw resulted in analgesia, but also in loss
      of its anxiogenic capacity. Inflammatory conditions induced changes in the CeA
      CCK signaling system with an increase of CCK immunoreactivity and a decrease in
      CCK1, but not CCK2, receptor mRNA. In CFA rats, patch-clamp experiments revealed
      that CCK infusion increased CeA neuron excitability. It also partially blocked
      the discharge of wide dynamic range neurons in the dorsal spinal cord. These
      effects of CCK on CeA and spinal neurons in CFA rats were mimicked by the
      specific CCK2 receptor agonist, gastrin. This analgesic effect was likely
      mediated by identified CeA neurons projecting to the periaqueductal gray matter
      that express CCK receptors. Together, our data demonstrate that intra-CeA CCK
      infusion activated a descending CCK2 receptor-dependent pathway that inhibited
      spinal neuron discharge. Thus, persistent pain induces a functional switch to a
      newly identified analgesic capacity of CCK in the amygdala, indicating central
      emotion-related circuit controls pain transmission in spinal cord.

PMID- 30281532
TI  - Reply to: Predictors of Opioid Administration in the Acute Postoperative Period.

PMID- 30281533
TI  - Efficacy of Neulasta or Neupogen on H-ARS and GI-ARS Mortality and Hematopoietic
      Recovery in Nonhuman Primates after 10 Gy Irradiation with 2.5% Bone-marrow
      Sparing.
AB  - A nonhuman primate model of acute, partial-body, high-dose irradiation with
      minimal (2.5%) bone-marrow sparing was used to assess endogenous gastrointestinal
      and hematopoietic recovery and the ability of Neulasta (pegylated granulocyte
      colony-stimulating factor) or Neupogen (granulocyte colony-stimulating factor) to
      enhance recovery from myelosuppression when administered at an increased interval
      between exposure and initiation of treatment. A secondary objective was to assess
      the effect of Neulasta or Neupogen on mortality and morbidity due to the
      hematopoietic acute radiation syndrome and concomitant gastrointestinal acute
      radiation syndrome. Nonhuman primates were exposed to 10.0 Gy, 6 MV, linear
      accelerator-derived photons delivered at 0.80 Gy min. All nonhuman primates
      received subject-based medical management. Nonhuman primates were dosed daily
      with control article (5% dextrose in water), initiated on day 1 postexposure;
      Neulasta (300 MUg kg), administered on days 1, 8, and 15 or days 3, 10, and 17
      postexposure; or Neupogen (10 MUg kg), administered daily postexposure following
      its initiation on day 1 or day 3 until neutrophil recovery (absolute neutrophil
      count >=1,000 cells MUL for 3 consecutive days). Mortality in the irradiated
      cohorts suggested that administration of Neulasta or Neupogen on either schedule
      did not affect mortality due to gastrointestinal acute radiation syndrome or
      mitigate mortality due to hematopoietic acute radiation syndrome (plus
      gastrointestinal damage). Following 10.0 Gy partial-body irradiation with 2.5%
      bone-marrow sparing, the mean duration of neutropenia (absolute neutrophil count
      <500 cells MUL) was 22.4 d in the control cohort vs. 13.0 and 15.3 d in the
      Neulasta day 1, 8, 15 and day 3, 10, 17 cohorts, relative to 16.2 and 17.4 d in
      the Neupogen cohorts initiated on day 1 and day 3, respectively. The absolute
      neutrophil count nadirs were 48 cells MUL in the controls; 117 cells MUL and 40
      cells MUL in the Neulasta days 1, 8, and 15 or days 3, 10, and 17 cohorts,
      respectively; and 75 cells MUL and 37 cells MUL in the Neupogen day 1 and day 3
      cohorts, respectively. Therefore, the earlier administration of Neulasta or
      Neupogen was more effective in this model of marginal 2.5% bone-marrow sparing.
      The approximate 2.5% bone-marrow sparing may approach the threshold for efficacy
      of the lineage-specific medical countermeasure. The partial-body irradiation with
      2.5% bone-marrow sparing model can be used to assess medical countermeasure
      efficacy in the context of the concomitant gastrointestinal and hematopoietic
      acute radiation syndrome sequelae.

PMID- 30281534
TI  - Blue laser imaging: a new image-enhanced endoscopy for the diagnosis of
      colorectal lesions.
AB  - BACKGROUND: Image-enhanced endoscopy enables real-time differential diagnosis of
      colorectal lesions through the observation of microvascular architecture.
      PURPOSE: To evaluate the efficacy of using blue laser imaging (BLI) for capillary
      pattern analysis in the differential diagnosis of neoplastic and non-neoplastic
      lesions. PATIENTS AND METHODS: This prospective study included 920 consecutive
      superficial lesions diagnosed in 457 patients. The capillary pattern was analysed
      using BLI-bright magnification on the basis of the Teixeira classification.
      Histopathology was used as the reference standard. RESULTS: The adenoma detection
      rate was 42.3%, with a mean of 0.95 adenomas per patient. Neoplastic lesions were
      predominant (70.3%), of which 33 (5.1%) had advanced histology. Neoplastic
      progression was significantly increased in patients aged at least 50 years, in
      lesions at least 10 mm and in lesions located in the right colon (P<0.01). BLI
      based capillary pattern analysis showed 95.5% accuracy, 95.7% sensitivity, 95.2%
      specificity, 97.9% positive predictive value and 90.3% negative predictive value
      in the diagnosis of neoplastic lesions. For 672 diminutive lesions (<=5 mm), BLI
      based capillary pattern analysis showed 95.7% accuracy, 96.6% sensitivity, 93.6%
      specificity, 97.2% positive predictive value and 92.2% negative predictive value.
      Analysing only lesions up to 5 mm in the rectum and sigmoid colon, the values
      were 95.2, 93.9, 96.5, 95.8 and 94.8%, respectively. CONCLUSION: BLI associated
      with magnification yielded excellent results for the real-time predictive
      histological diagnosis of colorectal lesions.

PMID- 30281535
TI  - Role of the von Willebrand factor and the VITRO score as predictors for variceal
      bleeding in patients with hepatitis C-related cirrhosis.
AB  - BACKGROUND: Noninvasive methods have been established to detect clinically
      significant portal hypertension in liver cirrhosis with variable limitations. The
      von Willebrand factor (vEF) has been found to increase in liver cirrhosis. AIM:
      The aim of this study was to explore the vEF and VITRO (von Willebrand factor
      antigen/platelet ratio) score in the prediction of variceal bleeding in patients
      with portal hypertension. MATERIALS AND METHODS: Fifty patients with hepatitis C
      related liver cirrhosis (25 patients with variceal bleeding and 25 without
      variceal bleeding) as well as 80 healthy controls were included. Laboratory
      investigations and upper gastrointestinal endoscopy were performed in all
      patients. Serum vEF was measured in the patient and the control group. The VITRO
      score was calculated. RESULTS: The mean levels of the vEF antigen and the VITRO
      score were higher in patients with variceal bleeding compared with patients
      without variceal bleeding and controls (P<0.001). At levels of at least 100.1
      ng/ml and at least 0.732, the vEF and the VITRO score could predict variceal
      bleeding with a sensitivity and a specificity of 92 and 99.9% for the vEF and 80
      and 68% for the VITRO score (area under the curve=0.982 and 0.843), respectively.
      Levels of vEF were correlated positively with esophageal varices grade.
      CONCLUSION: Serum vEF level and the VITRO score are potential noninvasive
      biomarkers for the prediction and risk stratification of variceal bleeding in
      hepatitis C-related liver cirrhosis.

PMID- 30281536
TI  - CaP Coating and Low-Level Laser Therapy to Stimulate Early Bone Formation and
      Improve Fixation of Rough Threaded Implants.
AB  - PURPOSE: This study aimed to compare in vivo osteogenesis on rough threaded
      dental implants with and without calcium phosphate (CaP) coating deposition,
      alone or in association with low-level laser therapy (LLLT) by gallium aluminum
      arsenide. MATERIAL AND METHODS: Four groups were studied: G1: implant; G2:
      implant + CaP coating; G3: implant + LLLT; and G4: implant + CaP coating + LLLT.
      LLLT was applied for 7 days at the surgical site before and after placing the
      implant. Topographic characterization was performed before surgery using scanning
      electron microscopy and energy dispersion spectrophotometry. Bone-implant contact
      (BIC) was measured after 1, 2, and 6 weeks and reverse torque after 6 weeks. In
      short periods, G2, G3, and G4 showed significantly greater BIC than G1 (P <
      0.05), but no difference in BIC was observed at 6 weeks. However, the values for
      the removal torque test at 6 weeks were higher in G2 and G4 (P < 0.05).
      CONCLUSION: Both CaP coating alone and using LLLT induce cellular stimulation and
      improve BIC in short-term healing, resulting in higher implant fixation, and
      should be considered in clinical practice due to their low cost and high
      effectiveness.

PMID- 30281537
TI  - The effects of P2X7 receptor knockout on emotional conditions over the lifespan
      of mice.
AB  - Neuroinflammation is one of the key factors contributing to depression. Recent
      studies have identified P2X7 receptor (P2X7r) as a major inflammatory regulator.
      However, the effects of P2X7r knockout (KO) on emotional conditions over the
      lifespan of mice are unknown. In this study, the effects of P2X7r deletion on
      emotional conditions over the lifespan of mice were investigated in young-aged (2
      month old), middle-aged (10 month old), and old-aged (18 month old) female P2X7r
      KO mice and age-matched female C57BL/6 mice. Behavioral tasks were conducted by
      open field test, forced swimming test and sucrose preference test. Mitochondrial
      structures and spine synapses in hippocampus were examined by electron
      microscopy. Enzyme-linked immunosorbent assay was used to analyze the expression
      of interleukin-1beta and tumor necrosis factor-alpha. Western blot analysis was
      used to assess the expression of nuclear factor-kappa B (NF-kappaB) pathway
      related proteins. The results indicated that middle-aged P2X7r KO mice displayed
      better emotional conditions than middle-aged WT mice. However, worse emotional
      conditions were observed in young-aged P2X7r KO mice. Moreover, abnormal
      mitochondrial structures and less spine synapses were observed in young-aged
      P2X7r KO mice. Mitochondrial structures were recovered and more spine synapses
      occurred in middle-aged P2X7r KO mice. In addition, expressions of interleukin
      1beta, tumor necrosis factor-alpha, p-IKKalpha, p-IKKbeta, p-IkappaBalpha, and p
      NF-kappaBp65 were decreased in middle-aged P2X7r KO mice, but increased in young
      aged P2X7r KO mice. In conclusion, P2X7r KO improves the emotional conditions at
      later stages of the lifespan of mice, but not in all ages, suggesting time
      specific roles of immune response in nervous system through NF-kappaB signaling
      pathway. Video abstract: http://links.lww.com/WNR/A494.

PMID- 30281539
TI  - Nocturnal hemodialysis: an underutilized modality?
AB  - PURPOSE OF REVIEW: There is increasing evidence that extended-hours regimens are
      associated with improved outcomes for patients on maintenance hemodialysis
      programs. Home hemodialysis programs are a well established way for patients to
      benefit from extended-hours dialysis overnight; however, there are significant
      barriers to home hemodialysis, which means that for many this is not an option.
      In center, nocturnal hemodialysis is an increasingly recognized way of offering
      extended-hours treatment to patients unable to undertake home-based programs and
      is an underutilized modality for such patients to gain from the physiological
      benefits of extended-hours dialysis regimens. RECENT FINDINGS: Recent data
      suggest that nocturnal dialysis programs confer a significant survival advantage
      over both standard dialysis and short-daily dialysis regimens with evidence
      proposing that this is mediated through beneficial cardiovascular remodeling.
      Moreover, there is strong evidence that nocturnal dialysis regimens associate
      with significant improvements in quality-of-life measures and social well being.
      SUMMARY: Nocturnal hemodialysis is an underutilized way of offering extended
      hours hemodialysis to patients in both the home and in-center environments. As
      the evidence base around nocturnal dialysis grows, clinicians and dialysis
      providers are becoming increasingly obliged to investigate implementation
      strategies for nocturnal dialysis services to improve patient outcomes and
      experience of care.

PMID- 30281540
TI  - Survival and Functional Status After Bridge-to-Transplant with a Left Ventricular
      Assist Device.
AB  - The use left ventricular assist devices (LVAD) as a bridge-to-transplant (BTT)
      has become a common modality to treat end-stage heart failure. We sought to
      examine the impact of BTT on long-term survival and quality of life after heart
      transplant. The population was all adult patients undergoing isolated heart
      transplantation in the United States between 2007 and 2017. Inclusion criteria
      covered BTT patients with a LVAD (only Heartmate II [HMII] or HeartWare
      Ventricular Assist System [HVAD]) and compared these with patients undergoing de
      novo heart transplantation. Our primary end-point was survival at 1, 2, and 5
      years. Secondary end-points were functional status, return to work, and rates of
      hospital readmission and graft rejection. Unconditional and conditional survival
      was estimated with the Kaplan-Meier method. The independent influence of BTT on
      risk-adjusted mortality was determined using Cox proportional hazards models. In
      this period, 5,584 patients were bridged with an LVAD and 12,295 underwent de
      novo transplantation. Unconditional survival was 2% higher in de novo patients at
      1, 2, and 5 years. After risk adjustment, BTT was associated with increased
      mortality at each time point. Unadjusted 5 year survival, conditional on 90 day
      survival, was similar between groups (82.6% vs. 83.4%; p = 0.15). Functional
      status, return to work, and unadjusted rates of hospital readmission and graft
      rejection were similar at 1, 2, 5 years. Bridge-to-transplant with LVADs provides
      excellent survival and similar quality of life to that of patients undergoing de
      novo heart transplantation. Bridge-to-transplant patients experience a slightly
      higher mortality rate within 90 days of transplantation.

PMID- 30281541
TI  - Clinical Outcomes of Impella Microaxial Devices Used to Salvage Cardiogenic Shock
      as a Bridge to Durable Circulatory Support or Cardiac Transplantation.
AB  - Temporary mechanical circulatory support (MCS) can be a bridge to decision for
      patients in severe cardiogenic shock who may be eligible for durable support or
      transplantation. Outcomes with Impella microaxial devices for salvage of severe
      shock in the end-stage heart failure population are not well described. Patients
      who underwent Impella placement as a bridge to decision, durable MCS, or
      transplantation were included. Eighty Impella devices (2.5 [1.3%], CP [53.8%],
      and 5.0 [45.0%]) were placed in 64 patients. Implant age was 56.2 +/- 12.5 years.
      Mean duration of assisted support was 13.2 +/- 15.1 days, and median duration per
      device was 7 days (interquartile range: 3-14). A total of 48.4% were in
      Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS 1)
      shock at implant, 51.6% in profile 2. Recent CPR (26.7%), ventilator use (67.2%),
      and extracorporeal membrane oxygenation (ECMO) use (26.7%) were frequent. Forty
      four of sixty four (68.8%) survived to next therapy: durable MCS (40.9%), OHT
      (36.4%), and recovery (22.7%). Overall 30 and 60 day survival were 67.2% and
      65.6%, respectively. Thirty and 60 day survival conditional on having survived to
      next therapy were 94.1% and 91.2%, respectively. Survivors were less likely to be
      on ventilators (p = 0.049) or continuous renal replacement therapy (p < 0.001)
      but were otherwise not different from nonsurvivors by age, sex, INTERMACS
      profile, CPR, prevalence of ischemic cardiomyopathy, among other characteristics.
      Sixteen patients were directly bridged to heart transplantation, and all were
      alive at long-term follow-up. Impella devices can be used to salvage patients in
      severe heart failure as a bridge to decision, durable MCS, or transplantation.
      Baseline demographics are not predictive of survival. Their use for this
      indication is increasing and further investigations are warranted.

PMID- 30281542
TI  - A Proof of Concept Study, Demonstrating Extracorporeal Carbon Dioxide Removal
      Using Hemodialysis with a Low Bicarbonate Dialysate.
AB  - Extracorporeal carbon dioxide removal (ECCO2R) devices remove CO2 directly from
      blood, facilitating ultraprotective ventilation or even providing an alternative
      to mechanical ventilation. However, ECCO2R is not widely available, whereas
      dialysis is available in most intensive care units (ICUs). Prior attempts to
      provide ECCO2R with dialysis, by removing CO2 in the form of bicarbonate, have
      been plagued by metabolic acidosis. We hypothesized that bicarbonate dialysis is
      feasible, provided the plasma strong ion difference is maintained. We used a
      mathematical model to investigate the effects of bicarbonate removal on pH and
      CO2 in plasma, and performed in-vitro experiments to test CO2 removal using three
      dialysates with different bicarbonate concentrations (0, 16, and 32 mmol.L). Our
      modeling predicted a reduction in partial pressures of CO2 (PCO2) and increased
      pH with progressive lowering of plasma bicarbonate, provided strong ion
      difference and plasma proteins (Atot) were maintained. In our in-vitro
      experiments, total CO2 removal, scaled up to an adult size filter, was highest
      with our dialysate containing no bicarbonate, where we removed the equivalent of
      94 ml.min (+/-3.0) of CO2. Under the same conditions, our dialysate containing a
      conventional bicarbonate concentration (32 mmol.L) only removed 5 ml.min (+/-4; p
      < 0.001). As predicted, pH increased following bicarbonate removal. Our data show
      that dialysis using low bicarbonate dialysates is feasible and result in a
      reduction in plasma PCO2. When scaled up, to estimate equivalent CO2 removal with
      an adult dialysis circuit, the amount removed competes with existing low-flow
      ECCO2R devices.

PMID- 30281543
TI  - An Innovative Ventricular Assist Device Strategy as a Bridge-to-Recovery in an
      Infant with Glenn Physiology.
AB  - Mechanical circulatory support for infants with single ventricle physiology
      remains challenging. Utilization of a ventricular assist device (VAD) has
      potential advantages over extracorporeal circulatory membrane oxygenation. As
      such, VAD utilization in single ventricle patients with refractory heart failure
      continues to be explored. Herein, we describe a novel VAD strategy to support an
      infant with Glenn physiology who presented in cardiogenic shock related to
      myocardial depression of unknown etiology. This VAD configuration supported the
      systemic circulation independent of the Glenn circulation. Seven days of VAD
      support resulted in recovery of myocardial and end-organ function leading to VAD
      removal. The patient remains alive and free from transplantation 16 months post
      VAD explantation.

PMID- 30281544
TI  - Development and Validation of a Life-Sized Mock Circulatory Loop of the Human
      Circulation for Fluid-Mechanical Studies.
AB  - Mock circulatory loops (MCLs) are usually developed for assessment of ventricular
      assist devices and consist of abstracted anatomical structures represented by
      connecting tubing pipes and controllable actuators which could mimic oscillating
      flow processes. However, with increasing use of short-term peripheral mechanical
      support (extracorporeal life support [ECLS]) and the upcoming evidence of even
      counteracting flow processes between the failing native circulation and ECLS,
      MCLs incorporating the peripheral vascular system and preserved anatomical
      structures are becoming more important for systematic assessment of these
      processes. For reproducible and standardized fluid-mechanical studies using
      magnetic resonance imaging, Doppler ultrasound, and computational fluid dynamics
      measurements, we developed a MCL of the human circulation. Silicon-based life
      sized dummies of the human aorta and vena cava (vascular module) were driven by
      paracorporeal pneumatic assist devices. The vascular module is placed in a
      housing with all arterial branches merging into peripheral resistance and
      compliances modules, and blood-mimicking fluid returns to the heart module
      through the venous dummy. Compliance and resistance chambers provide for an
      adequate simulation of the capillary system. Extracorporeal life support
      cannulation can be performed in the femoral and subclavian arteries and in the
      femoral and jugular veins. After adjusting vessel diameters using variable
      Hoffmann clamps, physiologic flow rates were achieved in the supraaortic
      branches, the renal and mesenteric arteries, and the limb arteries with
      physiologic blood pressure and cardiac output (4 L/min). This MCL provides a
      virtually physiologic platform beyond conventional abstracted MCLs for simulation
      of flow interactions between the human circulation and external circulation
      generated by ECLS.

PMID- 30281545
TI  - Anything Goes? High Time for Smart Blood Volume Monitors.

PMID- 30281546
TI  - Pediatric Candidemia Epidemiology and Morbidities: A Nationwide Cohort.
AB  - INTRODUCTION: Candidemia is the most frequent pediatric fungal infection, but
      incompletely elucidated in population-based settings. We performed a nationwide
      cohort study including all pediatric patients with candidemia in Denmark from
      2004-2014 to determine age, incidence, species distribution, underlying diseases,
      patient management and outcomes. METHODS: All candidemia episodes were identified
      through the active nationwide fungemia surveillance program. Susceptibility
      testing followed the EUCAST E.Def 7 reference method. Chi-squared test, Fisher's
      exact test and Venn diagrams were used for statistical analyses. RESULTS: 153
      pediatric patients (<=15 years) with 158 candidemia episodes were identified. The
      overall annual incidence rate was 1.3/100,000 population, higher for neonates
      (5.7/100,000 live births) and low birth weight (LBW) neonates (103.8/100.000 live
      births). From 2004-9 to 2010-2014, the proportion of C. albicans decreased from
      74.4% to 64.7%, whereas fluconazole resistance increased from 7.8% to 17.7%.
      Virtually all patients had at least one underlying disease (98.6%) and multi
      morbidity was common (43.5%, >=2 underlying diseases). Underlying diseases
      differed by age with heart malformations and gastrointestinal disease prevalent
      in children younger than 3 years. The overall 30-days mortality was 10.2% and
      highest for neonates (17.1%). Mortality increased from 2004- to 2010-14, driven
      by an increase among older children. DISCUSSION: This first nationwide
      epidemiologic study of pediatric candidemia confirmed a high incidence among
      neonates and a substantial burden of comorbidities. Moreover, an increasing
      proportion of fluconazole resistant non-albicans species was observed. Our
      findings underline the importance of choosing correct treatment and continuous
      surveillance of pediatric candidemia.

PMID- 30281547
TI  - Antibiotic Resistance Among Pediatric-Sourced Ocular Pathogens: 8-year Findings
      from the ARMOR Surveillance Study.
AB  - BACKGROUND: The Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR)
      study is a nationwide longitudinal antibiotic resistance surveillance program
      specific to bacterial pathogens commonly encountered in ocular infections. We
      evaluated resistance rates and trends among isolates obtained from pediatric
      patients (<=17 years of age). METHODS: Clinical centers across the US were
      invited to submit ocular isolates of Staphylococcus aureus, coagulase-negative
      staphylococci (CoNS), Streptococcus pneumoniae, Haemophilus influenzae, and
      Pseudomonas aeruginosa to a central laboratory. Minimum inhibitory concentrations
      (MICs) for various antibiotic classes were determined by broth microdilution per
      Clinical and Laboratory Standards Institute guidelines and interpreted as
      susceptible, intermediate, or resistant based on available breakpoints.
      Longitudinal trends were analyzed using a Cochran-Armitage test for linear trends
      in a proportion. RESULTS: Of 4829 isolates collected from January 2009-December
      2016, 995 isolates, sourced primarily from hospitals and referral centers, were
      obtained from pediatric patients (n=286 H. influenzae, n=284 S. aureus, n=213
      CoNS, n=150 S. pneumoniae, and n=62 P. aeruginosa). With few exceptions, P.
      aeruginosa and H. influenzae were generally susceptible to the antibiotics
      tested. Of S. aureus and CoNS isolates, respectively, 56% and 72% were resistant
      to azithromycin and 24% and 47% were methicillin-resistant (MR); concurrent
      resistance to other drug classes and multidrug resistance (>=3 drug classes) were
      prevalent among MR staphylococci. Of S. pneumoniae isolates, 38% and 35%
      demonstrated resistance to azithromycin and penicillin, respectively.
      Besifloxacin had the lowest MIC against the Gram-positive isolates. CONCLUSIONS:
      These in vitro data suggest antibiotic resistance is common among staphylococcal
      and pneumococcal isolates collected from pediatric patients with ocular
      infections. Methicillin resistance was prevalent among staphylococci with many
      strains demonstrating multidrug resistance. These findings may not be
      representative of resistance trends in community-based practices.

PMID- 30281548
TI  - Community Origins and Regional Differences Highlight Risk of Plasmid-Mediated
      Fluoroquinolone Resistant Enterobacteriaceae Infections in Children.
AB  - BACKGROUND: Fluoroquinolones (FQs) are uncommonly prescribed in children, yet
      pediatric multidrug-resistant (MDR)-Enterobacteriaceae (Ent) infections often
      reveal FQ resistance (FQR). We sought to define the molecular epidemiology of FQR
      and MDR-Ent in children. METHODS: A case-control analysis of children with MDR
      Ent infections at 3 Chicago hospitals was performed. Cases were children with
      third-generation-cephalosporin-resistant (3GCR) and/or carbapenem-resistant (CR)
      Ent infections. PCR and DNA analysis assessed bla and plasmid-mediated FQR
      (PMFQR) genes. Controls were children with 3GC and carbapenem susceptible-Ent
      infections matched by age, source and hospital. We assessed clinical
      epidemiologic predictors of PMFQR Ent infection. RESULTS: Of 169 3GCR and/or CR
      Ent isolates from children (median age 4.8 years), 85 were FQR; 56 (66%)
      contained PMFQR genes. The predominant organism was E. coli and most common bla
      gene blaCTX-M-1 group. In FQR isolates, PMFQR gene mutations included aac6'1b-cr,
      oqxA/B, qepA, and qnrA/B/D/S in 83%, 15%, 13% and 11% of isolates, respectively.
      FQR E. coli was often associated with phylogroup B2, ST43/ST131. On multivariable
      analysis, PMFQR Ent infections occurred mostly in outpatients (OR 33.1) of non
      black-white-Hispanic race (OR 6.5). Residents of Southwest Chicago were >5 times
      more likely to have PMFQR-Ent infections than those in the reference region,
      while residence in Central Chicago was associated with a 97% decreased risk.
      Other demographic, comorbidity, invasive-device, antibiotic use, or healthcare
      differences were not found. CONCLUSIONS: The strong association of infection with
      MDROs showing FQR with patient residence rather than with traditional risk
      factors suggests that the community environment is a major contributor to spread
      of these pathogens in children.

PMID- 30281550
TI  - Factors Associated With First Medication Time for Children Treated in the
      Emergency Department for Asthma.
AB  - OBJECTIVES: Acute asthma exacerbations are among the most common reasons for
      childhood emergency department (ED) visits and hospitalizations. Although early
      ED administration of asthma medication has been shown to decrease
      hospitalizations, studies of factors associated with early ED asthma medication
      delivery have been limited. The objective of our study was to identify patient-
      and ED-related factors associated with early medication delivery among children
      treated in the ED for asthma exacerbations. METHODS: This retrospective study
      used electronic health record data from all encounters for a primary diagnosis of
      asthma in an academic children's hospital ED during the study period 2009 to
      2013. Using multivariate logistic regression, we identified the association
      between patient- and ED-related factors and the time to first medication defined
      as a binary outcome using a threshold of 1 hour from ED arrival. We then
      stratified our analysis by triage level (Emergency Severity Index [ESI]).
      RESULTS: Of the 4846 encounters during the study period, 62% were male, mean age
      was 7.30 years, 76% had public insurance, and 57% had an ESI level of 3.
      Medication was administered within 1 hour of arrival in 2236 encounters (46%).
      After adjusting for covariates, multivariate logistic regression revealed that
      patients were less likely to have medications within 1 hour when they had less
      severe ESI (ESI 2 vs ESI 4: odds ratio [OR], 0.139; confidence interval [CI],
      0.114-0.170), arrived via non-emergency medical services (OR, 0.525; CI, 0.413
      0.665), or arrived to a crowded ED (OR, 0.574; CI, 0.505-0.652). Age, sex, and
      insurance type were not associated with timeliness of initial medication
      administration. Stratified analyses demonstrated that the crowding effect was
      larger for less severely ill patients. CONCLUSIONS: Our study found that patient
      severity (acuity level, arrival mode) and level of ED crowing-but not demographic
      factors-are associated with the administration of medication in the first hour to
      pediatric patients with asthma. Our findings may be helpful in redesigning asthma
      care management strategies.

PMID- 30281549
TI  - Disease- and Treatment-Related Morbidity in Adolescents With Perinatal HIV
      Infection in Asia.
AB  - BACKGROUND: Perinatally HIV-infected adolescents (PHIVA) are exposed to a chronic
      systemic infection and long-term antiretroviral therapy (ART), leaving them
      susceptible to morbidities associated with inflammation, immunodeficiency, and
      drug toxicity. METHODS: Data collected 2001-2016 from PHIVA aged 10-19 years
      within a regional Asian cohort were analysed using competing risk time-to-event
      and Poisson regression analyses to describe the nature and incidence of morbidity
      events and hospitalisations, and identify factors associated with disease
      related, treatment-related, and overall morbidity. Morbidity was defined
      according to WHO clinical staging criteria and US National Institutes of Health
      Division of AIDS criteria. RESULTS: A total 3,448 PHIVA contributed 17,778 person
      years. Median age at HIV diagnosis was 5.5 years and ART initiation was 6.9
      years. There were 2,562 morbidity events and 307 hospitalisations. Cumulative
      incidence for any morbidity was 51.7% and hospitalisation was 10.0%. Early
      adolescence was dominated by disease-related infectious morbidity, with a trend
      toward non-infectious and treatment-related morbidity in later adolescence.
      Higher overall morbidity rates were associated with a CD4 count <350 cells/uL,
      HIV viral load >=10,000 copies/mL, and experiencing prior morbidity at age <10
      years. Lower overall morbidity rates were found for those aged 15-19 years
      compared to 10-14 years, and those who initiated ART at age 5-9 years compared to
      <5 or >=10 years. CONCLUSIONS: Half of our PHIVA cohort experienced a morbidity
      event, with a trend from disease-related infectious events to treatment-related
      and non-infectious events as PHIVA age. Antiretroviral therapy initiation to
      prevent immune system damage, optimise virologic control, and minimise childhood
      morbidity are key to limiting adolescent morbidity.

PMID- 30281551
TI  - A Time-and-Motion Study of Clinical Trial Eligibility Screening in a Pediatric
      Emergency Department.
AB  - OBJECTIVE: Challenges with efficient patient recruitment including sociotechnical
      barriers for clinical trials are major barriers to the timely and efficacious
      conduct of translational studies. We conducted a time-and-motion study to
      investigate the workflow of clinical trial enrollment in a pediatric emergency
      department. METHODS: We observed clinical research coordinators during 3
      clinically staffed shifts. One clinical research coordinator was shadowed at a
      time. Tasks were marked in 30-second intervals and annotated to include patient
      screening, patient contact, performing procedures, and physician contact.
      Statistical analysis was conducted on the patient enrollment activities. RESULTS:
      We conducted fifteen 120-minute observations from December 12, 2013, to January
      3, 2014 and shadowed 8 clinical research coordinators. Patient screening took
      31.62% of their time, patient contact took 18.67%, performing procedures took
      17.6%, physician contact was 1%, and other activities took 31.0%. CONCLUSIONS:
      Screening patients for eligibility constituted the most time. Automated screening
      methods could help reduce this time. The findings suggest improvement areas in
      recruitment planning to increase the efficiency of clinical trial enrollment.

PMID- 30281552
TI  - Management of Wheezy Preschoolers in the Emergency Department: A Discrete Choice
      Experiment.
AB  - OBJECTIVES: This study aimed to elicit pediatric emergency physician's treatment
      choices for preschool-aged children with wheeze, determine the characteristics of
      the presenting child that influence treatment choices, and determine whether
      there is clinical equipoise by eliciting physician willingness to enroll these
      children in a placebo-controlled trial of corticosteroids. METHODS: Discrete
      choice experiments varying the characteristics of the presenting child were
      designed to elicit Canadian emergency physician's treatment choices, both in the
      emergency department (ED) and at discharge, for young children presenting with
      wheeze and their willingness to enroll in a randomized controlled trial (RCT).
      RESULTS: Most physicians chose to treat children with albuterol both in the ED
      and at discharge for all clinical scenarios. The proportion of physicians who
      chose to treat children with oral corticosteroids both in the ED and at discharge
      varied widely (from 12% to 81%) across all scenarios. Physician preference
      whether preschool children with wheeze should be treated with corticosteroids
      varied depending on the child's age, history of atopy, and previous and
      continuous wheeze. Between 73% and 86% of physicians were willing to enroll these
      children in an RCT indicating clinical equipoise. CONCLUSIONS: Physician
      treatment choices varied widely indicating clinical equipoise as to the
      effectiveness of corticosteroids in this population of patients. Management
      choices with respect to albuterol and corticosteroids were not consistent with
      published national and international guidelines. In line with this finding,
      physician's considerable willingness to enroll these children in an RCT may
      suggest that they are seeking guidance on how to manage these patients.

PMID- 30281553
TI  - Missed Diagnosis of Anaphylaxis in Patients With Pediatric Urticaria in Emergency
      Department.
AB  - OBJECTIVES: This study was to determine the characteristics of missed diagnosis
      of pediatric anaphylaxis that were registered as urticaria only at the emergency
      department (ED) by comparing those who had only urticaria symptoms with those who
      had both anaphylaxis and urticaria symptoms. METHODS: Subjects were classified
      into missed anaphylaxis and urticaria group according to whether satisfied
      anaphylaxis diagnostic criteria or not. Anaphylaxis group, those who were
      initially registered as anaphylaxis with urticaria and anaphylaxis symptoms
      simultaneously, were further investigated. RESULTS: The missed anaphylaxis group
      included 37 patients of 1051 pediatric urticaria patients. The anaphylaxis group
      included 11 patients. The time from symptom onset to ED arrival in the missed
      anaphylaxis group was shorter than the urticaria group. More patients in the
      missed anaphylaxis group had a history of past food allergy. Seafood, egg, and
      milk were more common causes of allergy in the missed anaphylaxis group; however,
      idiopathic causes were more common in the urticaria group. Symptom was more
      severe in the missed anaphylaxis group than the urticaria group. More treatments
      except antihistamine were performed at ED in the missed anaphylaxis group.
      Cardiovascular symptoms were more common in the anaphylaxis group than the missed
      anaphylaxis group. CONCLUSIONS: Of all pediatric urticaria patients, 3.5% of
      patients were not registered as anaphylaxis although they had anaphylaxis
      symptoms. Missed diagnosis of anaphylaxis in pediatric urticaria patients at ED
      was associated with a history of past food allergy, milk, egg, and seafood as
      causes of allergy, treated with fluid administration, steroid, and epinephrine.

PMID- 30281554
TI  - Prehospital Analgesic Administration by Parents for Pain Relief in Children.
AB  - PURPOSE: Undertreatment of pain by caregivers before presentation to the
      pediatric emergency department (ED) has been well documented. What has yet to be
      elucidated are the reasons why caregivers fail to adequately treat pain before
      arrival in the ED and whether there are differences based on ethnic background or
      age of the child. The objectives of this study were to determine the barriers to
      giving pain medication for injuries before ED arrival and to determine if there
      are any ethnic- or age-related variations to giving pain relief at home. METHODS:
      This prospective descriptive study was conducted in the ED at a tertiary care,
      freestanding children's hospital with a current annual census of approximately
      80,000. An anonymous prospective questionnaire was given to caregivers of
      children between 2 and 17 years of age presenting to the ED between August 2013
      and September, 2014. The study population was obtained as a convenience sample.
      All were self-referred with chief complaints of head, ear, or extremity pain. The
      questionnaire asked about pain medications and doses given at home as well as the
      reasons parents gave medication or refused to give pain medication before
      arrival. Charts were then abstracted to obtain demographic information and care
      received in the ED. RESULTS: A total of 154 (45.6%) of the 338 patients enrolled
      did not receive pain relief before coming to the ED. There were no differences in
      pain medication received at home based on ethnicity (P = 0.423) or age (P =
      0.580). Parents could choose from a list of multiple reasons as to why pain
      medications were given and/or free text their own answer. The main reasons given
      by parents were that the accident did not happen at home (28.6%) and that they
      did not have time to give pain relief before coming to the ED (13%). Other common
      answers were "had no pain relievers at home" (12.4%) or "afraid it would be
      wrong/harmful/did not want to mask symptoms" (9.2%). Seventeen parents responded
      that their child did not complain of pain. Overall, only 28.1% of participants
      stated lack of pain medications at home. CONCLUSIONS: In this study,
      approximately half of all children receive an analgesic for their painful
      condition before coming to the ED. Continued education regarding pain relief
      before coming to the ED is needed. Future studies will focus on educating parents
      to provide analgesia at home.

PMID- 30281555
TI  - Detectability of Brain Metastases by Using Frequency-Selective Nonlinear Blending
      in Contrast-Enhanced Computed Tomography.
AB  - PURPOSE: The aim of this study to evaluate the role of frequency-selective
      nonlinear blending (FS-NLB) for the detectability of brain metastases with
      contrast-enhanced computed tomography (CECT) using magnetic resonance imaging
      (MRI) as standard of reference. MATERIALS AND METHODS: A retrospective patient
      data search at our institution yielded 91 patients who underwent both brain CECT
      and MRI for screening of brain metastases (n = 173) between 2014 and 2016 (mean
      time interval, 29 +/- 37 [malignant: 15 +/- 16/benign: 42 +/- 47] days). A
      recently introduced FS-NLB postprocessing technique was applied to CECT images.
      Two readers interpreted all CT images in an independent fashion. The
      conventional, linear blending (LB) CT images were evaluated first. After a
      washout period, the same readers evaluated the FS-NLB CT images. The standard of
      reference was established by a consensus interpretation of the brain MRI studies.
      Outcome variables included determination of best performing FS-NLB settings,
      region of interest (ROI)-based calculation of contrast-to-noise ratios (CNRs),
      size, and number of brain metastases. Based on the number of metastases, we
      classified patients in 5 therapeutically relevant categories (0, no metastasis;
      1, singular metastasis; 2, less than 4 metastases; 3, >4 and <10 metastases; 4,
      >10 metastases). Statistical comparison and diagnostic performance tests were
      applied. RESULTS: A center of 47 Hounsfield units (HU), delta of 5 HU, and slope
      of 5 resulted in the best delineation of hyperdense brain metastases, whereas for
      hypodense brain metastases, a center of 32 HU, delta of 5 HU, and slope of 5
      showed best delineation. Frequency-selective nonlinear blending significantly
      increased CNR in hyperdense cerebral metastases (CECT: 9.11 [6.9-10.9], FS-NLB:
      18.1 [11.9-22.8]; P < 0.0001) and hypodense cerebral metastases (CECT: 6.3 [5.2
      8], FS-NLB: 17.8 [14.5-19.7]; P < 0.0001). Sensitivity, specificity, negative
      predictive values, positive predictive values, and accuracy for LB, and FS-NLB
      were 40%, 98%, 99%, 31%, and 52%, and 62%, 94%, 97%, 40%, and 69%, respectively.
      Magnetic resonance imaging, LB, and FS-NLB classification of metastatic patients
      were group 0 (47, 47, 46), group 1 (14, 8, 11), group 2 (16, 12, 15), group 3 (8,
      7, 8), and group 4 (6, 4, 6). CONCLUSIONS: Frequency-selective nonlinear blending
      postprocessing of CECT significantly increases the detection of brain metastases
      over conventional CECT; however, the sensitivity remains lower than MRI.
      Frequency-selective nonlinear blending is slightly inferior in the categorization
      of patients into therapeutically relevant groups, when compared with MRI.

PMID- 30281556
TI  - Clinical Feasibility of Gadoxetic Acid-Enhanced Isotropic High-Resolution 3
      Dimensional Magnetic Resonance Cholangiography Using an Iterative Denoising
      Algorithm for Evaluation of the Biliary Anatomy of Living Liver Donors.
AB  - OBJECTIVES: The aim of this study was to evaluate the clinical feasibility of
      gadoxetic acid-enhanced isotropic high-resolution (IHR) 3-dimensional (3D) T1
      weighted (T1W) magnetic resonance cholangiography (MRC) using an iterative
      denoising (ID) algorithm for evaluation of the biliary anatomy of living liver
      donors in comparison with conventional 3D multislice T2-weighted (T2W) MRC.
      MATERIALS AND METHODS: In this institutional review board-approved retrospective
      study, a total of 75 living liver donors who underwent conventional 3D multislice
      T2W-MRC and IHR-3D-T1W-MRC on a 3 T scanner and subsequent right hepatectomy for
      liver donation were included. Isotropic high-resolution T1W-MRCs were obtained in
      both axial and coronal planes using the 3D VIBE Dixon sequence and an ID
      algorithm implemented with wavelet thresholding of 3D complex-valued data of the
      noise level, g-factor, and k-space filtering. Thereafter, 3 board-certified
      radiologists independently reviewed the examinations for visibility and sharpness
      of the bile ducts (BDs), as well as overall image quality on a 5-point scale. For
      diagnostic performance, anatomic variations of the BD, length of right hepatic
      duct, and the expected number of BD openings at right hepatectomy were also
      recorded. As the reference standard, BD variation was determined by surgeons in
      consensus using intraoperative real-time fluorescent cholangiography. RESULTS:
      Mean acquisition times of 3D-T2W-MRC and IHR-T1W-MRC were 367 seconds and 17
      seconds (P < 0.001), respectively. Compared with 3D-T2W-MRCs, IHR-T1W-MRCs
      yielded significantly improved visibility and sharpness of all evaluated
      intrahepatic bile ducts (all Ps < 0.05), and higher overall image quality (P <
      0.01). The IHR-T1W-MRCs also demonstrated significantly higher agreement in BD
      variation (87.6% vs 81.3%, P = 0.03) and expected BD openings (76.9% vs 70.2%, P
      = 0.006) than 3D-T2W-MRC compared with the reference standard. Interobserver
      agreement in estimating the length of right hepatic duct, IHR-T1W-MRC showed
      excellent interobserver agreement (intraclass correlation coefficient, 0.94),
      whereas 3D-T2W-MRC showed good interobserver agreement (intraclass correlation
      coefficient, 0.78). CONCLUSIONS: Isotropic high-resolution T1W-MRCs with ID
      provided significantly improved BD image quality and more accurate depiction of
      the BD anatomy and BD openings at right donor hemihepatetomy than 3D-T2W-MRC.

PMID- 30281557
TI  - Synthetic 2-Dimensional Mammography Can Replace Digital Mammography as an Adjunct
      to Wide-Angle Digital Breast Tomosynthesis.
AB  - OBJECTIVES: The aim of this study was to evaluate the detection rate and
      diagnostic performance of 2-dimensional synthetic mammography (SM) as an adjunct
      to wide-angle digital breast tomosynthesis (WA-DBT) compared with digital
      mammography (DM) alone or to DM in combination with WA-DBT. MATERIALS AND
      METHODS: There were 205 women with 179 lesions included in this retrospective
      reader study. Patients underwent bilateral, 2-view (2v) DM and WA-DBT between
      March and June 2015. The standard of reference was histology and/or 1-year
      stability at follow-up. Four blinded readers randomly evaluated images according
      to the BI-RADS lexicon from 3 different protocols: 2v DM alone, 2v DM with 2v WA
      DBT, and 2v SM with 2v WA-DBT. Detection rate, sensitivity, specificity, and
      accuracy were calculated and compared using multivariate analysis. Readers'
      confidence and image quality were evaluated. RESULTS: The detection rate ranged
      from 68.7% to 79.9% for DM, 76.5% to 84.4% for DM with WA-DBT, and 73.2% to 84.9%
      for SM with WA-DBT. Sensitivity and accuracy were significantly higher when DBT
      was available (P < 0.001). Specificity did not differ significantly between DM
      only, DM with WA-DBT, or SM with WA-DBT (P >= 0.846). Wide-angle DBT combined
      readings did not differ between SM and DM in terms of sensitivity, specificity,
      and accuracy (P >= 0.341). Readers' confidence and image quality was rated good
      to excellent. CONCLUSIONS: Wide-angle DBT combined with DM or SM increases
      sensitivity and accuracy without reducing specificity compared with DM alone.
      Wide-angle DBT combined readings did not differ between SM and DM; therefore, SM
      should replace DM for combined readings with WA-DBT.

PMID- 30281559
TI  - Living donor liver transplant from an HIV-positive individual to an HIV-negative
      individual: could this become a new reality?

PMID- 30281558
TI  - Living donor liver transplant from an HIV-positive mother to her HIV-negative
      child: opening up new therapeutic options.
AB  - OBJECTIVE: Transplant a liver from an HIV-positive mother to her HIV-negative
      child to save the child's life. DESIGN: A unique case of living donor liver
      transplantation from an HIV-positive mother to her HIV-negative child in South
      Africa. Two aspects of this case are ground-breaking. First, it involves living
      donation by someone who is HIV-positive and second it involves controlled
      transplant of an organ from an HIV-positive donor into an HIV-negative recipient,
      with the potential to prevent infection in the recipient. METHODS: Standard
      surgical procedure for living donor liver transplantation at our centre was
      followed. HIV-prophylaxis was administered preoperatively. Extensive,
      ultrasensitive HIV testing, over and above standard diagnostic assays, was
      undertaken to investigate recipient serostatus and is ongoing. RESULTS: Both
      mother and child are well, over 1 year posttransplantation. HIV seroconversion in
      our recipient was detected with serological testing at day 43 posttransplant.
      However, a decline in HIV antibody titres approaching undetectable levels is now
      being observed. No plasma, or cell-associated HIV-1 DNA has been detected in the
      recipient at any time-point since transplant. CONCLUSION: This case potentially
      opens up a new living liver donor pool which might have clinical relevance in
      countries where there is a high burden of HIV and a limited number of deceased
      donor organs or limited access to transplantation. However, our recipient's HIV
      status is equivocal at present and additional investigation regarding
      seroconversion events in this unique profile is ongoing.

PMID- 30281560
TI  - Secondary anal cancer prevention in the HIV-infected: a step ahead but a long way
      to go.

PMID- 30281561
TI  - Ocular syphilis, an old adversary is back in the old world too!

PMID- 30281562
TI  - Distinct paradoxical inflammatory reaction followed by postantiretroviral therapy
      immune reconstitution syndrome in cryptococcal meningitis.

PMID- 30281563
TI  - Severe refractory hidradenitis suppurativa successfully treated with adalimumab
      in an HIV-positive/hepatitis C virus-positive patient.

PMID- 30281564
TI  - Pediatric Critical Care Medicine: Serving Our Missions While Maintaining
      Excellence.

PMID- 30281565
TI  - Pediatric Delirium: Where Do We Go From Here?

PMID- 30281566
TI  - Interleukin-1 Receptor Antagonist and Interleukin-1beta: Risk Marker or Risk
      Factor for Pediatric Acute Respiratory Distress Syndrome?

PMID- 30281567
TI  - The SCARF Trial: A Veiled Statement on the PICU?

PMID- 30281568
TI  - Artificial Intelligence in Pediatric Critical Care Medicine: Are We (Finally)
      Ready?

PMID- 30281569
TI  - Phenotyping in Pediatric Traumatic Brain Injury.

PMID- 30281570
TI  - Venoarterial Extracorporeal Membrane Oxygenation in Severe Pediatric Septic
      Shock.

PMID- 30281571
TI  - Vancomycin Pharmacokinetics During Extracorporeal Membrane Oxygenation and Dosing
      Targets-A Constantly Moving Target?

PMID- 30281572
TI  - Artificial Intelligence: An Inkling of Caution.

PMID- 30281574
TI  - All Delirium May Not Be Created Equal: Consideration of Differential Effects of
      Delirium Based Upon Underlying Etiology.

PMID- 30281573
TI  - Understanding Disseminated Intravascular Coagulation and Hepatobiliary
      Dysfunction Multiple Organ Failure in Hyperferritinemic Critical Illness.

PMID- 30281575
TI  - Food for Thought-Pediatric Critical Illness and Feeding Outcomes.

PMID- 30281576
TI  - Physician Awareness and Management Practices of Fluid Overload in Critically Ill
      Children.

PMID- 30281577
TI  - A Quality Improvement Bundle Including Pay for Performance for the
      Standardization of Order Set Use in Moderate Asthma.
AB  - OBJECTIVE: In order to standardize use of our hospital's computerized asthma
      order set, which was developed based on an asthma clinical practice guideline,
      for moderately ill children presenting for care of asthma, we developed a quality
      improvement bundle, including a time-limited pay-for-performance component, for
      pediatric emergency department and pediatric urgent care faculty members.
      METHODS: Following baseline measurement, we used a run-in period for education,
      feedback, and improvement of the asthma order set. Then, faculty members earned
      0.1% of salary during each of 10 successive months (evaluation period) in which
      the asthma order set was used in managing 90% or more of eligible patients.
      RESULTS: At baseline, the asthma order set was used in managing 60.5% of eligible
      patients. Order set use rose sharply during the run-in period. During the 10
      month evaluation period, use of the asthma order set was significantly above
      baseline, with a mean of 91.6%; faculty earned pay-for-performance bonuses during
      8 of 10 possible months. Following completion of the evaluation period, asthma
      order set use remained high. CONCLUSIONS: A quality improvement bundle, including
      a time-limited pay-for-performance component, was associated with a sustained
      increase in the use of a computerized asthma order set for managing moderately
      ill asthmatic children.

PMID- 30281578
TI  - Infectious Endocarditis Prophylaxis in Children.
AB  - Infectious endocarditis (IE) is a rare illness with high morbidity and mortality.
      Incidence of IE is on the rise in industrialized countries, particularly as those
      with congenital heart defects are living longer and the use of indwelling central
      catheters increases. With the 2007 American Heart Association guidelines, there
      has been a shift in recommending antibiotic prophylaxis only to high-risk patient
      populations. This clinical review will highlight the changing epidemiology and
      etiology of IE, followed by an emphasis on the appropriate indications for
      antibiotic prophylaxis in high-risk populations undergoing specific procedures.

PMID- 30281580
TI  - A Case of Intracardiac Invasion of Hepatoblastoma Diagnosed With Point-of-Care
      Ultrasound.
AB  - Ultrasonography can be useful in the evaluation of children with abdominal
      complaints and may be the initial imaging modality in patients presenting with a
      newly recognized abdominal mass. Hepatoblastoma is an uncommon cause of acute
      abdominal pain in children and can rarely metastasize to the heart through
      vascular invasion. We report a case in which a 4-year-old girl who presented to
      the emergency department with abdominal pain promptly underwent point-of-care
      ultrasound and was subsequently diagnosed with intracardiac invasion of an
      abdominal tumor.

PMID- 30281581
TI  - Development and Pilot Testing of a Computerized Asthma Kiosk to Initiate Chronic
      Asthma Care in a Pediatric Emergency Department.
AB  - OBJECTIVES: Emergency department (ED) visits are an opportunity to initiate
      chronic asthma care. Ideally, this care should be implemented in a fashion that
      limits utilization of scarce ED resources. We developed, iteratively refined, and
      pilot tested the feasibility of a computerized asthma kiosk to (1) capture asthma
      information, (2) deliver asthma education, and (3) facilitate guideline-based
      chronic asthma management. METHODS: The following are the 4 phases of this study:
      (1) developing the content and structure of a computerized asthma kiosk, (2)
      iterative refinement through heuristic testing by human-computer interface
      experts, (3) usability testing with ED providers (n = 4) and caregivers of
      children with asthma (n = 4), and (4) pilot testing the kiosk with caregivers (n
      = 31) and providers in the ED (n = 18). Outcome measures for the pilot-testing
      phase were the proportion of ED providers who prescribed long-term controller
      medication (LTCM) and asthma action plans (AsAPs) and the proportion of children
      who took LTCMs and attended primary care providers follow-up. RESULTS: After
      kiosk development and refinement, pilot implementation resulted in LTCMs
      prescribing and AsAP provision for 19 (61%) of 31 and 17 (55%) of 31 patients,
      respectively. Before kiosk use, the proportion of the 18 ED providers who
      reported prescribing LTCM was 1 (5%) of 18, and providing AsAPs was 0 (0%) of 18.
      Eighteen (58%) of the 31 caregivers reported that their children used LTCMs after
      kiosk use and 13 (42%) of 31 reported following up with the primary care provider
      within 1 month of the ED visits. CONCLUSIONS: A rigorously developed asthma kiosk
      showed promise for initiating chronic asthma care in the ED.

PMID- 30281582
TI  - Comparing Performance of Airtraq Versus Macintosh Laryngoscope for Pediatric
      Intubation by Novices.

PMID- 30281583
TI  - Predictive Factors of Perforated Appendicitis in Children Younger Than 5 Years.

PMID- 30281584
TI  - Red Ear Syndrome in a Pediatric Patient.

PMID- 30281585
TI  - Curcumin Induces Autophagy via Inhibition of Yes-Associated Protein (YAP) in
      Human Colon Cancer Cells.
AB  - BACKGROUND Colon cancer is one of the most common cancers and it is the fourth
      leading cause of cancer-related deaths worldwide. YAP can promote cell
      proliferation and inhibit apoptosis, leading to loss of cell contact inhibition
      and promoting malignant cell transformation. MATERIAL AND METHODS In this study
      we analyzed the effects of different curcumin concentrations on the proliferation
      of colon cancer cells using MTT and colony formation assays. Western blot
      detection was performed to confirm the YAP, LC3-II, and P62 expression. RESULTS
      Curcumin inhibited proliferation and promoted colon cancer cell autophagy. In
      addition, Western blot results indicated that curcumin suppressed YAP expression
      in colon cancer cells. To assess the mechanism, we treated the cell lines with
      curcumin and assessed YAP overexpression and YAP knockdown. The results revealed
      that curcumin inhibits the proliferation and promotes autophagy of these cell
      lines. Western blot results showed that curcumin reversed the effect of YAP in
      colon cancer cells. CONCLUSIONS Our results suggest that YAP has great promise
      for treatment of colon cancer and that it might be a potential diagnostic marker
      for colon cancer.

PMID- 30281586
TI  - Smooth super-twisting sliding mode control for the class of underactuated
      systems.
AB  - In this article, Smooth Super-twisting Sliding Mode Control (SSTWSMC) is
      investigated for the class of underactuated system. In underactuated systems, the
      control design is not directly applicable as for other systems (known as fully
      actuated systems). Therefore, at initial step, a nonlinear uncertain model of
      systems is transformed into the controllable canonical form, and then Smooth
      Super Twisting (SSTW) based Sliding Mode Control (SMC) is devised for the control
      design purpose for the considered class. In addition, closed loop stability of
      the proposed technique is presented in a fascinating way. The effectiveness and
      supremacy of the proposed control technique is proven by extensive analysis
      between conventional Sliding Mode Control (SMC), Super twisting (STW) sliding
      mode control and Smooth Super-twisting Sliding Mode Control (SSTWSMC). The
      comprehensive analysis evaluates the attributes like robustness enhancement,
      settling time, control effort, chattering reduction, overshoot, sliding mode
      convergence, etc. and is supported by simulations as well as practical
      implementation on ball and beam balancer (which is considered as application
      example).

PMID- 30281588
TI  - Violence detection in surveillance video using low-level features.
AB  - It is very important to automatically detect violent behaviors in video
      surveillance scenarios, for instance, railway stations, gymnasiums and
      psychiatric centers. However, the previous detection methods usually extract
      descriptors around the spatiotemporal interesting points or extract statistic
      features in the motion regions, leading to limited abilities to effectively
      detect video-based violence activities. To address this issue, we propose a novel
      method to detect violence sequences. Firstly, the motion regions are segmented
      according to the distribution of optical flow fields. Secondly, in the motion
      regions, we propose to extract two kinds of low-level features to represent the
      appearance and dynamics for violent behaviors. The proposed low-level features
      are the Local Histogram of Oriented Gradient (LHOG) descriptor extracted from RGB
      images and the Local Histogram of Optical Flow (LHOF) descriptor extracted from
      optical flow images. Thirdly, the extracted features are coded using Bag of Words
      (BoW) model to eliminate redundant information and a specific-length vector is
      obtained for each video clip. At last, the video-level vectors are classified by
      Support Vector Machine (SVM). Experimental results on three challenging benchmark
      datasets demonstrate that the proposed detection approach is superior to the
      previous methods.

PMID- 30281587
TI  - Cross-resistance is modular in bacteria-phage interactions.
AB  - Phages shape the structure of natural bacterial communities and can be effective
      therapeutic agents. Bacterial resistance to phage infection, however, limits the
      usefulness of phage therapies and could destabilise community structures,
      especially if individual resistance mutations provide cross-resistance against
      multiple phages. We currently understand very little about the evolution of cross
      resistance in bacteria-phage interactions. Here we show that the network
      structure of cross-resistance among spontaneous resistance mutants of Pseudomonas
      aeruginosa evolved against each of 27 phages is highly modular. The cross
      resistance network contained both symmetric (reciprocal) and asymmetric
      (nonreciprocal) cross-resistance, forming two cross-resistance modules defined by
      high within- but low between-module cross-resistance. Mutations conferring cross
      resistance within modules targeted either lipopolysaccharide or type IV pilus
      biosynthesis, suggesting that the modularity of cross-resistance was structured
      by distinct phage receptors. In contrast, between-module cross-resistance was
      provided by mutations affecting the alternative sigma factor, RpoN, which
      controls many lifestyle-associated functions, including motility, biofilm
      formation, and quorum sensing. Broader cross-resistance range was not associated
      with higher fitness costs or weaker resistance against the focal phage used to
      select resistance. However, mutations in rpoN, providing between-module cross
      resistance, were associated with higher fitness costs than mutations associated
      with within-module cross-resistance, i.e., in genes encoding either
      lipopolysaccharide or type IV pilus biosynthesis. The observed structure of cross
      resistance predicted both the frequency of resistance mutations and the ability
      of phage combinations to suppress bacterial growth. These findings suggest that
      the evolution of cross-resistance is common, is likely to play an important role
      in the dynamic structure of bacteria-phage communities, and could inform the
      design principles for phage therapy treatments.

PMID- 30281589
TI  - Tooth crown tissue proportions and enamel thickness in Early Pleistocene Homo
      antecessor molars (Atapuerca, Spain).
AB  - Tooth crown tissue proportions and enamel thickness distribution are considered
      reliable characters for inferring taxonomic identity, phylogenetic relationships,
      dietary and behavioural adaptations in fossil and extant hominids. While most
      Pleistocene hominins display variations from thick to hyper-thick enamel,
      Neanderthals exhibit relatively thinner. However, the chronological and
      geographical origin for the appearance of this typical Neanderthal condition is
      still unknown. The European late Early Pleistocene species Homo antecessor (Gran
      Dolina-TD6 site, Sierra de Atapuerca) represents an opportunity to investigate
      the appearance of the thin condition in the fossil record. In this study, we aim
      to test the hypothesis if H. antecessor molars approximates the Neanderthal
      condition for tissue proportions and enamel thickness. To do so, for the first
      time we characterised the molar inner structural organization in this Early
      Pleistocene hominin taxon (n = 17) and compared it to extinct and extant
      populations of the genus Homo from African, Asian and European origin (n = 355).
      The comparative sample includes maxillary and mandibular molars belonging to H.
      erectus, East and North African Homo, European Middle Pleistocene Homo,
      Neanderthals, and fossil and extant H. sapiens. We used high-resolution images to
      investigate the endostructural configuration of TD6 molars (tissue proportions,
      enamel thickness and distribution). TD6 permanent molars tend to exhibit on
      average thick absolute and relative enamel in 2D and 3D estimates, both in the
      complete crown and the lateral enamel. This condition is shared with the majority
      of extinct and extant hominin sample, except for Neanderthals and some isolated
      specimens. However, while the total crown percentage of dentine in TD6 globally
      resembles the low modern values, the lateral crown percentage of dentine tends to
      be much higher, closer to the Neanderthal signal. Similarly, the H. antecessor
      molar enamel distribution maps reveal a relative distribution pattern that is
      more similar to the Neanderthal condition (with the thickest enamel more spread
      at the periphery of the occlusal basin) rather than that of other fossil
      specimens and modern humans (with thicker cuspal enamel). Future studies on
      European Middle Pleistocene populations will provide more insights into the
      evolutionary trajectory of the typical Neanderthal dental structural
      organization.

PMID- 30281590
TI  - Leisure time activities as mediating variables in functional disability
      progression: An application of parallel latent growth curve modeling.
AB  - OBJECTIVES: The aims of this study were to investigate (1) whether and (2) the
      extent to which Taiwanese older adults' leisure time activity (LTA) trajectories
      mediated the potential association between their sociodemographic factors and
      their functional disability trajectories. METHODS: Longitudinal data from four
      waves of the Taiwan Longitudinal Study on Aging (TLSA), collected between 1996
      and 2007, were used for analysis (N = 3,429). Parallel-process latent growth
      curve modeling was adopted to evaluate the process by which LTA mediated between
      sociodemographic factors (age, gender, education, self-rated health,
      comorbidities, and depression) and the outcome process of functional
      disabilities. RESULTS: When mediated by baseline level of LTA, five
      sociodemographic factors-age, gender, education level, self-rated health, and
      number of comorbidities-had significant and negative mediating effects on
      baseline or change in functional disability, thus improving disability outcomes.
      However, four of the sociodemographic factors (age, education level, and number
      of comorbidities), when mediated through the rate of change in LTA, were found to
      have significant and positive mediating effects, which increased disability
      levels. The proportion of effects mediated by the LTA trajectory ranged from 0%
      to 194%. DISCUSSION: The large proportion of effects mediated through the LTA
      process underlines the importance of LTA to public health policy and health
      programs for older adults. The study's findings shed light on how to better
      target populations of older adults to promote an active lifestyle and achieve
      more successful aging in late life in Asian countries.

PMID- 30281592
TI  - Wrangling distributed computing for high-throughput environmental science: An
      introduction to HTCondor.
AB  - Biologists and environmental scientists now routinely solve computational
      problems that were unimaginable a generation ago. Examples include processing
      geospatial data, analyzing -omics data, and running large-scale simulations.
      Conventional desktop computing cannot handle these tasks when they are large, and
      high-performance computing is not always available nor the most appropriate
      solution for all computationally intense problems. High-throughput computing
      (HTC) is one method for handling computationally intense research. In contrast to
      high-performance computing, which uses a single "supercomputer," HTC can
      distribute tasks over many computers (e.g., idle desktop computers, dedicated
      servers, or cloud-based resources). HTC facilities exist at many academic and
      government institutes and are relatively easy to create from commodity hardware.
      Additionally, consortia such as Open Science Grid facilitate HTC, and commercial
      entities sell cloud-based solutions for researchers who lack HTC at their
      institution. We provide an introduction to HTC for biologists and environmental
      scientists. Our examples from biology and the environmental sciences use
      HTCondor, an open source HTC system.

PMID- 30281591
TI  - Comparison of ultrasound imaging and cone-beam computed tomography for
      examination of the alveolar bone level: A systematic review.
AB  - BACKGROUND AND OBJECTIVE: The current methods to image alveolar bone in humans
      include intraoral 2D radiography and cone-beam computed tomography (CBCT).
      However, these methods expose the subject to ionizing radiation. Therefore,
      ultrasound imaging has been investigated as an alternative technique, as it is
      both non-invasive and free from ionizing radiation. In order to assess the
      validity and reliability of ultrasonography in visualizing alveolar bone, a
      systematic review was conducted comparing ultrasound imaging to CBCT for
      examination of the alveolar bone level. STUDY DESIGN: Seven databases were
      searched. Studies addressing examination of alveolar bone level via CBCT and
      ultrasound were selected. Risk of bias under Cochrane guidelines was used as a
      methodological quality assessment tool. RESULTS: All the four included studies
      were ex vivo studies that used porcine or human cadaver samples. The alveolar
      bone level was measured by the distance from the alveolar bone crest to certain
      landmarks such as cemento-enamel junction or gingival margin. The risk of bias
      was found as low. The mean difference between ultrasound and CBCT measurements
      ranged from 0.07 mm to 0.68 mm, equivalent to 1.6% - 8.8%. CONCLUSIONS: There is
      currently preliminary evidence to support the use of ultrasonography as compared
      to CBCT for the examination of alveolar bone level. Further studies comparing
      ultrasound to gold standard methods would be necessary to help validate the
      accuracy of ultrasonography as a diagnostic technique in periodontal imaging.

PMID- 30281593
TI  - Photosynthesis by marine algae produces sound, contributing to the daytime
      soundscape on coral reefs.
AB  - We have observed that marine macroalgae produce sound during photosynthesis. The
      resultant soundscapes correlate with benthic macroalgal cover across shallow
      Hawaiian coral reefs during the day, despite the presence of other biological
      noise. Likely ubiquitous but previously overlooked, this source of ambient
      biological noise in the coastal ocean is driven by local supersaturation of
      oxygen near the surface of macroalgal filaments, and the resultant formation and
      release of oxygen-containing bubbles into the water column. During release,
      relaxation of the bubble to a spherical shape creates a monopole sound source
      that 'rings' at the Minnaert frequency. Many such bubbles create a large,
      distributed sound source over the sea floor. Reef soundscapes contain vast
      quantities of biological information, making passive acoustic ecosystem
      evaluation a tantalizing prospect if the sources are known. Our observations
      introduce the possibility of a general, volumetrically integrative, noninvasive,
      rapid and remote technique for evaluating algal abundance and rates of primary
      productivity in littoral aquatic communities. Increased algal cover is one of the
      strongest indicators for coral reef ecosystem stress. Visually determining
      variations in algal abundance is a time-consuming and expensive process. This
      technique could therefore provide a valuable tool for ecosystem management but
      also for industrial monitoring of primary production, such as in algae-based
      biofuel synthesis.

PMID- 30281594
TI  - "I should have started earlier, but I was not feeling ill!" Perceptions of
      Kalenjin women on antenatal care and its implications on initial access and
      differentials in patterns of antenatal care utilization in rural Uasin Gishu
      County Kenya.
AB  - AIM: The aim of this study was to explore how Kalenjin women in rural Uasing
      Gishu County in Kenya perceive antenatal care and how their perceptions impede or
      motivate earlier access and continuous use of antenatal care services. METHODS: A
      study was conducted among 188 pregnant and post-natal mothers seeking care in 23
      rural public health facilities. Gestational age at the initial antenatal care
      booking was established from their medical cards. Further researcher-administered
      questionnaire with closed and open-ended questions was used. Key informant
      interviews with traditional birth attendants (n = 6) and maternal and child
      health nursing officers (n = 6) were also conducted for triangulation.
      Descriptive statistics were applied using SPSS programme. The interviews of women
      who gave consent to be audio recorded (n = 52) were transcribed and thematically
      analysed using MAXQDA program, based on Andersen and Newman's (1973) behavioural
      model of health services utilization. RESULTS: The mean gestational age at
      booking initial biomedical care was 23.36 weeks. Only 18 patients (10%) booked
      before 13 weeks and 45% made four or more visits. The main reasons given for
      early booking were: illness in index pregnancy (42%) checking the foetus position
      and monitoring foetus progress (7%). The main reasons given for late booking
      were: no reason (31%), was not feeling sick (16%), fear or shame due to
      unexpected pregnancy (13%). Almost half of the respondents (44%) used both
      biomedical and traditional antenatal care services. Main reasons for visiting
      traditional care were to: check foetus position and reposition it (63%), collect
      medicinal herbs (31%), relief discomforts through massage (18%). CONCLUSION:
      Early antenatal care booking is meant for women with unpleasant physical signs
      and symptoms. Later ANC is meant to check foetus position and reposition it to
      cephalic presentation and monitor its progress and this is only possible if the
      foetus is large.

PMID- 30281595
TI  - The Middle Pleistocene (MIS 12) human dental remains from Fontana Ranuccio
      (Latium) and Visogliano (Friuli-Venezia Giulia), Italy. A comparative high
      resolution endostructural assessment.
AB  - The penecontemporaneous Middle Pleistocene sites of Fontana Ranuccio (Latium) and
      Visogliano (Friuli-Venezia Giulia), set c. 450 km apart in central and
      northeastern Italy, respectively, have yielded some among the oldest human fossil
      remains testifying to a peopling phase of the Italian Peninsula broadly during
      the glacial MIS 12, a stage associated with one among the harshest climatic
      conditions in the Northern hemisphere during the entire Quaternary period.
      Together with the large samples from Atapuerca Sima de los Huesos, Spain, and
      Caune de l'Arago at Tautavel, France, the remains from Fontana Ranuccio and
      Visogliano are among the few mid-Middle Pleistocene dental assemblages from
      Western Europe available for investigating the presence of an early Neanderthal
      signature in their inner structure. We applied two- three-dimensional techniques
      of virtual imaging and geometric morphometrics to the high-resolution X-ray
      microtomography record of the dental remains from these two Italian sites and
      compared the results to the evidence from a selected number of Pleistocene and
      extant human specimens/samples from Europe and North Africa. Depending on their
      preservation quality and on the degree of occlusal wear, we comparatively
      assessed: (i) the crown enamel and radicular dentine thickness topographic
      variation of a uniquely represented lower incisor; (ii) the lateral crown tissue
      proportions of premolars and molars; (iii) the enamel-dentine junction, and (iv)
      the pulp cavity morphology of all available specimens. Our analyses reveal in
      both samples a Neanderthal-like inner structural signal, for some aspects also
      resembling the condition shown by the contemporary assemblage from Atapuerca SH,
      and clearly distinct from the recent human figures. This study provides
      additional evidence indicating that an overall Neanderthal morphological dental
      template was preconfigured in Western Europe at least 430 to 450 ka ago.

PMID- 30281596
TI  - Preservative effect of Chinese cabbage (Brassica rapa subsp. pekinensis) extract
      on their molecular docking, antioxidant and antimicrobial properties.
AB  - This study aimed at investigating the antimicrobial activity of different solvent
      extracts of Chinese cabbage Brassica rapa subsp. pekinensis (BRARP) and their
      antioxidant and cytotoxicity properties. Of the different solvents extracts, the
      chloroform extracts (CE) were significantly inhibited the bacterial pathogens at
      minimum inhibitory concentration (MIC) of 16.5 mg.mL-1. Biochemical analysis
      revealed that total phenol (62.6 +/- 0.05 mg GAE.g-1) and flavonoids (27.6 +/-
      0.04 mg QE.g-1) were higher in the extracts of BRARP, which resulted in enhanced
      antioxidant activity in CE. A total of eight dominant compounds were detected in
      the potent antimicrobial extract from BRARP based on GC-MS analysis. The
      molecular interactions study revealed that, among the screened compounds the 1,2
      benzenedicarboxylic acid and 2,3-dicyanopropionamide interacted with the active
      site of pathogenicity and survival related protein with lipopolysaccharide (LpxC)
      with higer binding energy. This work concluded that the 1, 2-Benzenedicarboxylic
      acid and 2, 3-Dicyanopropionamide from BRARP was reported to be good non
      cytotoxic and antioxidant antimicrobials against bacterial pathogens.

PMID- 30281597
TI  - Eprobe mediated RT-qPCR for the detection of leukemia-associated fusion genes.
AB  - The detection and quantification of leukemia-associated fusion gene transcripts
      play important roles in the diagnosis and follow-up of leukemias. To establish a
      standardized method without interlaboratory discrepancies, we developed a novel
      one-step reverse transcription quantitative PCR (RT-qPCR) assay, called "the
      Eprobe leukemia assay," for major and minor BCR-ABL1, RUNX1-RUNX1T1, and various
      isoforms of PML-RARA. This assay is comprised of Eprobes that are exciton
      controlled hybridization-sensitive fluorescent oligonucleotides. Melting curve
      analyses were performed on synthetic quantitative standard RNAs with strict
      quality control. Quantification capacity was evaluated by comparison with TaqMan
      RT-qPCR using 67 primary leukemia patient samples. The lower limit of detection
      and the limit of quantification of this assay were less than 31.3 copies/reaction
      and 62.5 copies/reaction, respectively. This assay correctly detected the fusion
      genes in samples with 100% sensitivity and specificity. The specificity of the
      reactions was confirmed by melting curve analyses. The assay detected low-level
      expression of minor BCR-ABL1 co-expressed with major BCR-ABL1. These results
      illustrate the feasibility and high accuracy of the Eprobe leukemia assay, even
      for minimal residual disease monitoring.

PMID- 30281598
TI  - Typhoid fever outbreak in the Democratic Republic of Congo: Case control and
      ecological study.
AB  - During 2011 a large outbreak of typhoid fever affected an estimated 1430 people
      in Kikwit, Democratic Republic of Congo. The outbreak started in military camps
      in the city but then spread to the general population. This paper reports the
      results of an ecological analysis and a case-control study undertaken to examine
      water and other possible transmission pathways. Attack rates were determined for
      health areas and risk ratios were estimated with respect to spatial exposures.
      Approximately 15 months after the outbreak, demographic, environmental and
      exposure data were collected for 320 cases and 640 controls residing in the worst
      affected areas, using a structured interview questionnaire. Unadjusted and
      adjusted odds ratios were estimated. Complete data were available for 956
      respondents. Residents of areas with water supplied via gravity on the mains
      network were at much greater risk of disease acquisition (risk ratio = 6.20,
      95%CI 3.39-11.35) than residents of areas not supplied by this mains network. In
      the case control study, typhoid was found to be associated with ever using tap
      water from the municipal supply (OR = 4.29, 95% CI 2.20-8.38). Visible urine or
      faeces in the latrine was also associated with increased risk of typhoid and
      having chosen a water source because it is protected was negatively associated.
      Knowledge that washing hands can prevent typhoid fever, and stated habit of
      handwashing habits before cooking or after toileting was associated with
      increased risk of disease. However, observed associations between handwashing or
      plate-sharing with disease risk could very likely be due to recall bias. This
      outbreak of typhoid fever was strongly associated with drinking water from the
      municipal drinking water supply, based on the descriptive and analytic
      epidemiology and the finding of high levels of faecal contamination of drinking
      water. Future outbreaks of potentially waterborne disease need an integrated
      response that includes epidemiology and environmental microbiology during early
      stages of the outbreak.

PMID- 30281599
TI  - Eldecalcitol is more effective in promoting osteogenesis than alfacalcidol in
      Cyp27b1-knockout mice.
AB  - Calcium (Ca) absorption from the intestinal tract is promoted by active vitamin D
      (1alpha,25D3). Vitamin D not only promotes Ca homeostasis, but it also inhibits
      bone resorption and promotes osteogenesis, thus playing a role in the maintenance
      of normal bone metabolism. Because 1alpha,25D3 plays an important role in
      osteogenesis, vitamin D formulations, such as alfacalcidol (ALF) and eldecalcitol
      (ELD), are used for treating osteoporosis. While it is known that, in contrast to
      ALF, ELD is an active ligand that directly acts on bone, the reason for its
      superior osteogenesis effects is unknown. Cyp27b1-knockout mice (Cyp27b1-/-mice)
      are congenitally deficient in 1alpha,25D3 and exhibit marked hypocalcemia and
      high parathyroid hormone levels, resulting in osteodystrophy involving bone
      hypocalcification and growth plate cartilage hypertrophy. However, because the
      vitamin D receptor is expressed normally in Cyp27b1-/-mice, they respond normally
      to 1alpha,25D3. Accordingly, in Cyp27b1-/-mice, the pharmacological effects of
      exogenously administered active vitamin D derivatives can be analyzed without
      being affected by 1alpha,25D3. We used Cyp27b1-/-mice to characterize and clarify
      the superior osteogenic effects of ELD on the bone in comparison with ALF. The
      results indicated that compared to ALF, ELD strongly induces ECaC2, calbindin
      D9k, and CYP24A1 in the duodenum, promoting Ca absorption and decreasing the
      plasma concentration of 1alpha,25D3, resulting in improved osteogenesis. Because
      bone morphological measurements demonstrated that ELD has stronger effects on
      bone calcification, trabecular formation, and cancellous bone density than ALF,
      ELD appears to be a more effective therapeutic agent for treating postmenopausal
      osteoporosis, in which cancellous bone density decreases markedly. By using
      Cyp27b1-/-mice, this study was the first to succeed in clarifying the osteogenic
      effect of ELD without any influence of endogenous 1alpha,25D3. Furthermore, ELD
      more strongly enhanced bone mineralization, trabecular proliferation, and
      cancellous bone density than did ALF. Thus, ELD is expected to show an effect on
      postmenopausal osteoporosis, in which cancellous bone mineral density decreases
      markedly. In the future, this study may enable the development of next-generation
      active vitamin D derivatives with higher affinity for bone than ELD.

PMID- 30281600
TI  - Vancomycin associated acute kidney injury in pediatric patients.
AB  - INTRODUCTION: Vancomycin associated acute kidney injury (vAKI) is a well known
      complication in pediatric patients. Identification and characterization of the
      incidence and risk factors for vAKI in the pediatric population would assist
      clinicians in potentially preventing or mitigating vAKI. METHODS AND MATERIALS: A
      6 year retrospective cohort study was designed. Patients were included if they
      were < 19 years of age, received vancomycin as inpatients, and had a baseline SCr
      and one other SCr drawn during and up to 72 hours after the discontinuation of
      vancomycin. Data collection included patient demographics, vancomycin doses and
      length of therapy, vancomycin serum concentrations, and concomitant medications.
      The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to
      characterize acute kidney injury. Descriptive statistical methods were used and
      ordinal logistic regression was employed to determine variables significantly
      associated with vAKI. RESULTS: A total of 7,095 patients met study criteria
      (55.4% male, median age 4.1 years (IQR 0.67-11.2 years)). Mechanical ventilation
      was used in 7.9% (n = 563) and mortality was 4.9% (n = 344). A total of 153
      concomitant medications were identified. A median of 5 (IQR 3-7) SCr values were
      obtained and median SCr prior to vancomycin was 0.39 (IQR 0.28-0.57) mg/dL (CrCl
      134+/-58 mL/min/1.73m2). Vancomycin was administered for a median of 2 (IQR 1-3)
      days (14.9+/-1.6 mg/kg/dose). vAKI was present in 12.2% (n = 862: KDIGO stage 1
      (8.30%, n = 589), KDIGO stage 2 (1.94%, n = 138) KDIGO stage 3 (1.89%, n = 134)).
      Mean vancomycin serum concentration at 6-8 hours after a dose for patients with
      vAKI (10.7+/-8.9 mg/L) was significantly, but not clinically different for
      patients with no vAKI (7.5+/-6.3 mg/L). (p<0.05) Ordinal logistic regression
      identified total dose of vancomycin, vancomycin administration in the intensive
      care unit, and concomitant medication administration as significant for vAKI. In
      particular, concomitant administration of several different medications,
      including nafcillin, clindamycin, and acetazolamide, were noted for strong
      associations with vAKI. (p<0.05). CONCLUSIONS: Moderate to severe acute kidney
      injury due to vancomycin is infrequent in children and associated with
      concomitant medication use and total dose of vancomycin. Serum vancomycin
      concentrations are not useful predictors of vAKI in the pediatric population.

PMID- 30281602
TI  - 90,000 year-old specialised bone technology in the Aterian Middle Stone Age of
      North Africa.
AB  - The question of cognitive complexity in early Homo sapiens in North Africa is
      intimately tied to the emergence of the Aterian culture (~145 ka). One of the
      diagnostic indicators of cognitive complexity is the presence of specialised bone
      tools, however significant uncertainty remains over the manufacture and use of
      these artefacts within the Aterian techno-complex. In this paper we report on a
      bone artefact from Aterian Middle Stone Age (MSA) deposits in Dar es-Soltan 1
      cave on the Atlantic coast of Morocco. It comes from a layer that can be securely
      dated to ~90 ka. The typological characteristics of this tool, which suggest its
      manufacture and use as a bone knife, are comparatively similar to other bone
      artefacts from dated Aterian levels at the nearby site of El Mnasra and
      significantly different from any other African MSA bone technology. The new find
      from Dar es-Soltan 1 cave combined with those from El Mnasra suggest the
      development of a bone technology unique to the Aterian.

PMID- 30281601
TI  - Learning-induced ribosomal RNA is required for memory consolidation in mice
      Evidence of differentially expressed rRNA variants in learning and memory.
AB  - The transition from short-term to long-term forms of synaptic plasticity requires
      protein synthesis and new gene expression. Most efforts to understand experience
      induced changes in neuronal gene expression have focused on the transcription
      products of RNA polymerase II-primarily mRNAs and the proteins they encode. We
      recently showed that nucleolar integrity and activity-dependent ribosomal RNA
      (rRNA) synthesis are essential for the maintenance of hippocampal long-term
      potentiation (LTP). Consequently, the synaptic plasticity and memory hypothesis
      predicts that nucleolar integrity and activity dependent rRNA synthesis would be
      required for Long-term memory (LTM). We tested this prediction using the
      hippocampus-dependent, Active Place Avoidance (APA) spatial memory task and found
      that training induces de novo rRNA synthesis in mouse dorsal hippocampus. This
      learning-induced increase in nucleolar activity and rRNA synthesis persists at
      least 24 h after training. In addition, intra-hippocampal injection of the Pol I
      specific inhibitor, CX-5461 prior to training, revealed that de novo rRNA
      synthesis is required for 24 h memory, but not for learning. Using qPCR to assess
      activity-dependent changes in gene expression, we found that of seven known rRNA
      expression variants (v-rRNAs), only one, v-rRNA IV, is significantly upregulated
      right after training. These data indicate that learning induced v-rRNAs are
      crucial for LTM, and constitute the first evidence that differential rRNA gene
      expression plays a role in memory.

PMID- 30281603
TI  - Informed consent learning: Needs and preferences in medical clerkship
      environments.
AB  - PURPOSE: Limited information exists regarding students' routine educational needs
      in support of ethics and professionalism practices faced in real clinical
      practice. As such the authors aimed to explore medical students learning needs
      and preferences for informed consent and relevant ethical issues in the clerkship
      environments. MATERIALS AND METHODS: A cross-sectional study using a self
      administered, printed survey distributed to final year clinical clerks. RESULTS:
      84% completed the survey. Students indicated the need for more attention to all
      topics related to informed consent (mean = 7.1 on a scale of 0 to 9; +/-1.2).
      Most additional instructional attention was requested for topics raised in
      discussions with patients concerning the risks, benefits and alternatives to
      recommended treatments (7.3 +/-1.4). The cohort expressed the need for education
      in the care of vulnerable patients (7.2 +/-1.2) with a maximum score for the care
      of abused children. Women perceived greater need for education concerning
      informed consent than male respondents (p>0.05). There were significant
      differences between students who scored high or low on the item "being treated in
      professional manner" and "endorsement of educational needs for care of
      adolescents" (p = 0.05). CONCLUSION: There was heightened perception among final
      year medical students of the need for greater attention to be paid to informed
      consent education.

PMID- 30281604
TI  - Oral cholera vaccine coverage during a preventive door-to-door mass vaccination
      campaign in Nampula, Mozambique.
AB  - BACKGROUND: In addition to improving water, sanitation and hygiene (WASH)
      measures and optimal case management, the introduction of Oral cholera vaccine
      (OCV) is a complementary strategy for cholera prevention and control for
      vulnerable population groups. In October 2016, the Mozambique Ministry of Health
      implemented a mass vaccination campaign using a two-dose regimen of the
      ShancholTM OCV in six high-risk neighborhoods of Nampula city, in Northern
      Mozambique. Overall 193,403 people were targeted by the campaign, which used a
      door-to-door strategy. During campaign follow-up, a population survey was
      conducted to assess: (1) OCV coverage; (2) frequency of adverse events following
      immunization; (3) vaccine acceptability and (4) reasons for non-vaccination.
      METHODOLOGY/PRINCIPAL FINDINGS: In the absence of a household listing and clear
      administrative neighborhood delimitations, we used geospatial technology to
      select households from satellite images and used the support of community
      leaders. One person per household was randomly selected for interview. In total,
      636 individuals were enrolled in the survey. The overall vaccination coverage
      with at least one dose (including card and oral reporting) was 69.5% (95%CI: 51.2
      88.2) and the two-dose coverage was 51.2% (95%CI: 37.9-64.3). The campaign was
      well accepted. Among the 185 non-vaccinated individuals, 83 (44.6%) did not take
      the vaccine because they were absent when the vaccination team visited their
      houses. Among the 451 vaccinated individuals, 47 (10%) reported minor and non
      specific complaints, and 78 (17.3%) mentioned they did not receive any
      information before the campaign. CONCLUSIONS/SIGNIFICANCE: In spite of overall
      coverage being slightly lower than expected, the use of a mobile door-to-door
      strategy remains a viable option even in densely-populated urban settings. Our
      results suggest that campaigns can be successfully implemented and well accepted
      in Mozambique in non-emergency contexts in order to prevent cholera outbreaks.
      These findings are encouraging and complement the previous Mozambican experience
      related to OCV.

PMID- 30281605
TI  - A prospective matched study on symptomatic dengue in pregnancy.
AB  - Dengue fever is an increasing problem worldwide, but consequences during
      pregnancy remain unclear. Much of the available literature suffers from
      methodological biases that compromise the validity of clinical recommendations.
      We conducted a matched cohort study during an epidemic in French Guiana to
      compare events and pregnancy outcomes between two paired groups of pregnant
      women: women having presented with symptomatic dengue during pregnancy (n = 73)
      and women having had neither fever nor dengue during pregnancy (n = 219). Women
      in each arm were matched by place of follow up, gestation weeks at inclusion, and
      place of residence. Dengue infection was considered to be confirmed if viral RNA,
      N S1 antigen, the seroconversion of IgM antibodies or the presence of IgM was
      detected in collected samples. According to the 2009 WHO classification, 27% of
      the women with symptomatic dengue had at least one clinical or biological warning
      sign. These complications occurred after the 28th week of gestation in 55% of
      cases. The medical history, socioeconomic status and demographic characteristics
      were included in multivariate analysis. Exposure to dengue during pregnancy was
      not significantly associated with prematurity, small for gestational age infants,
      hypertension or emergency caesarian section. Maternal dengue with warning signs
      was a risk factor for peripartum hemorrhage with adjusted relative risk = 8.6(95%
      CI = 1.2-62). There was a near significant association between dengue and in
      utero death (p = 0.09). This prospective comparative study underlined the
      importance of taking into account potential confounders between exposure to
      dengue and the occurrence of obstetrical events. It also confirms the need for
      increased vigilance for pregnant women with dengue, particularly for women who
      present with severe dengue.

PMID- 30281606
TI  - Receiving a hug is associated with the attenuation of negative mood that occurs
      on days with interpersonal conflict.
AB  - Interpersonal touch is emerging as an important topic in the study of adult
      relationships, with recent research showing that such behaviors can promote
      better relationship functioning and individual well-being. This investigation
      considers whether being hugged is associated with reduced conflict-related
      decreases in positive affect and increases in negative affect as well as whether
      these associations differ between women and men. A sample of 404 adults were
      interviewed every night for 14 consecutive days about their conflicts, hug
      receipt, and positive and negative affect. Results indicated that there was an
      interaction between hug receipt and conflict exposure such that receiving a hug
      was associated with a smaller conflict-related decrease in positive affect and a
      smaller conflict-related increase in negative affect when assessed concurrently.
      Hug receipt was also prospectively associated with a smaller conflict-related
      increase in next day negative affect but was not associated with next day
      positive affect. Associations between hug receipt and conflict-related changes in
      affect did not differ between women and men, between individuals who were married
      or in a marital-like relationship and those who were not, or as a function of
      individual differences in baseline perceived social support. While correlational,
      these results are consistent with the hypothesis that hugs buffer against
      deleterious changes in affect associated with experiencing interpersonal
      conflict. Possible mechanisms through which hugs facilitate positive adaptation
      to conflict are discussed.

PMID- 30281607
TI  - Conditioned increase of locomotor activity induced by haloperidol.
AB  - Dopamine antagonist drugs have profound effects on locomotor activity. In
      particular, the administration of the D2 antagonist haloperidol produces a state
      that is similar to catalepsy. In order to confirm whether the modulation of the
      dopaminergic activity produced by haloperidol can act as an unconditioned
      stimulus, we carried out two experiments in which the administration of
      haloperidol was repeatedly paired with the presence of distinctive contextual
      cues that served as a Conditioned Stimulus. Paradoxically, the results revealed a
      dose-dependent increase in locomotor activity following conditioning with
      dopamine antagonist (Experiments 1) that was susceptible of extinction when the
      conditioned stimulus was presented repeatedly by itself after conditioning
      (Experiment 2). These data are interpreted from an associative perspective,
      considering them as a result of a classical conditioning process.

PMID- 30281608
TI  - Evaluation of a set of refolded recombinant antigens for serodiagnosis of human
      fascioliasis.
AB  - Diagnosis of fascioliasis with high sensitivity and specificity antigens play a
      vital role in the management of the disease. Majority of commercial serological
      tests use F. hepatica native antigens and indicate wide diversities in test
      accuracy. Nowadays, recombinant antigens have been introduced as diagnostic
      reagents offer better test standardization. A combination of highly pure
      recombinant antigens associated with correct folding will leads to improve
      specificity and sensitivity of ELISA for diagnosis of Fascioliasis. In this
      article, Fasciola hepatica saposin-like protein 2 (SAP-2), ferritin protein (Ftn
      1) and leucine aminopeptidase (LAP) recombinant antigens were considered as tools
      for the detection of F. hepatica immunoglobulin G antibodies in persons with
      chronic human fasciolasis. The recombinant antigens were obtained as fusion
      proteins, expressed in Escherichia coli and purified by immobilized metal
      affinity chromatography (IMAC). The refolding processes of denatured recombinant
      proteins were performed using dialysis method in the presence of chemical
      additives, and reduced/oxidized glutathione (in vitro). The immunoreactivity of
      the recombinant antigens was assessed individually and in a combination compared
      with excretory/secretory antigen (E/S) in an enzyme-linked immunosorbent assay
      (ELISA) test. The experiments were optimized using 213 serum samples from humans,
      including patients with chronic fascioliasis, patients with other parasitic
      diseases, and healthy subjects. The results indicated 95% sensitivity and 98%
      specificity for rtFhSAP-2, 96% sensitivity and 91% specificity for E/S, 80% and
      83.3% for rtFhFtn-1, 84% and 88% for FhLAP, and also, 96% and 95% for combination
      of recombinant antigens, respectively. In conclusion, the results of this
      investigation showed that rtFhSAP-2 with the highest specificity and acceptable
      sensitivity has a considerable superiority compared to mentioned antigens and
      even in combination with these antigens in serodiagnosis of human fascioliasis.

PMID- 30281609
TI  - Thismia kelabitiana (Thismiaceae), a new unique Fairy Lantern from Borneo
      potentially threatened by commercial logging.
AB  - Thismia kelabitiana, a new unique species from the Sarawak state of Malaysia in
      the island of Borneo is described and illustrated. This new species is not
      similar to any species of Thismia described so far especially by having a unique
      form of mitre and outer perianth lobes deeply divided into 8-10 acute lobes and
      forming striking fringe around perianth tube opening. The species appears to be
      critically endangered due to ongoing logging activities in the region. It may
      potentially become a surrogate species for lower montane forests of the region
      and thus help protect them against further destruction.

PMID- 30281611
TI  - Turbulent particle pair diffusion: A theory based on local and non-local
      diffusional processes.
AB  - A re-appraisal of the Richardson's 1926 dataset [Richardson, L. F. Proc. Roy.
      Soc. Lond. A 100, 709-737, (1926)] displays an unequivocal non-local scaling for
      the pair diffusion coefficient, [Formula: see text], quite different to the
      previously assumed locality scaling law [Formula: see text], where sigmal is the
      pair separation. Consequently, the foundations of turbulent pair diffusion theory
      are re-examined here and it is shown that pair diffusion is governed by both
      local and non-local diffusional processess inside the inertial subrange. In the
      context of generalised energy spectra, E(k) ~ k-p for 1 < p <= 3, the new theory
      predicts two non-Richardson regimes depending on the size of the inertial
      subrange: (1) in the limit of asymptotically infinite subrange, non-local scaling
      laws is obtained, [Formula: see text], with gamma intermediate between the purely
      local and the purely non-local scalings, i.e. (1 + p)/2 < gamma <= 2; and (2) for
      finite (short) inertial subrange, local scaling laws are obtained, [Formula: see
      text]. The theory features a novel mathematical approach expressing the pair
      diffusion coefficient through a Fourier integral decomposition.

PMID- 30281610
TI  - Widespread detections of neonicotinoid contaminants in central Wisconsin
      groundwater.
AB  - Neonicotinoids are a popular and widely-used class of insecticides whose heavy
      usage rates and purported negative impacts on bees and other beneficial insects
      has led to questions about their mobility and accumulation in the environment.
      Neonicotinoid compounds are currently registered for over 140 different crop uses
      in the United States, with commercial growers continuing to rely heavily on
      neonicotinoid insecticides for the control of key insect pests through a
      combination of in-ground and foliar applications. In 2008, the Wisconsin
      Department of Agriculture, Trade and Consumer Protection (DATCP) began testing
      for neonicotinoids in groundwater test wells in the state, reporting detections
      of one or more neonicotinoids in dozens of shallow groundwater test wells. In
      2011, similar detection levels were confirmed in several high-capacity overhead
      center-pivot irrigation systems in central Wisconsin. The current study was
      initiated to investigate the spatial extent and magnitude of neonicotinoid
      contamination in groundwater in and around areas of irrigated commercial
      agriculture in central Wisconsin. From 2013-2015 a total of 317 samples were
      collected from 91 unique high-capacity irrigation wells and tested for the
      presence of thiamethoxam (TMX), a neonicotinoid, using enzyme-linked
      immunosorbent assays. 67% of all samples were positive for TMX at a concentration
      above the analytical limit of quantification (0.05 MUg/L) and 78% of all wells
      tested positive at least once. Mean detection was 0.28 MUg/L, with a maximum
      detection of 1.67 MUg/L. Five wells had at least one detection exceeding 1.00
      MUg/L. Furthermore, an analysis of the spatial structure of these well detects
      suggests that contamination profiles vary across the landscape, with differences
      in mean detection levels observed from landscape (25 km), to farm (5 km), to
      individual well (500 m) scales. We also provide an update of DATCP's
      neonicotinoid monitoring in Wisconsin's shallow groundwater test wells and
      private potable wells for the years 2011-2017.

PMID- 30281612
TI  - Mechanism of sea-ice expansion in the Indian Ocean sector of Antarctica: Insights
      from satellite observation and model reanalysis.
AB  - In the backdrop of global warming, Antarctic sea-ice variability showed an
      overall expansion with the regional heterogeneity of increasing and decreasing
      patterns. Analysis of satellite derived sea-ice extent, during 1979 to 2015, in
      the Indian Ocean sector of Antarctica (IOA) revealed expansion of 2.4+/-1.2%
      decade-1. We find strengthening of westerly wind during the austral summer
      (between 50 degrees S to 62 degrees S) facilitated northward advection of a cool
      and fresh layer. Also, the strong westerly wind cools the upper ocean due to net
      heat loss from the ocean surface. The combined effect of northward advection of
      cold fresh layer and net heat loss from the surface, favours sea-ice expansion in
      the subsequent seasons, in the IOA region, north of 62 degrees S. However, sea
      ice retreat was observed near the Kerguelen Plateau, due to upper ocean warming,
      and hence a non-annular pattern of sea-ice extent in the IOA was observed.

PMID- 30281613
TI  - In patients with unilateral pleural effusion, restricted lung inflation is the
      principal predictor of increased dyspnoea.
AB  - BACKGROUND AND OBJECTIVE: The mechanism of dyspnoea associated with pleural
      effusion is uncertain. A cohort of patients requiring thoracoscopy for unilateral
      exudative effusion were investigated for associations between dyspnoea and
      suggested predictors: impaired ipsilateral diaphragm movement, effusion volume
      and restricted lung inflation. METHODS: Baseline Dyspnoea Index, respiratory
      function, and ultrasound assessment of ipsilateral diaphragm movement were
      assessed prior to thoracoscopy, when effusion volume was measured. Transitional
      Dyspnoea Index (change from baseline) was assessed 4 and 8 weeks after
      thoracoscopy. Pearson product moment assessed bivariate correlations and a
      general linear model examined how well total lung capacity (measuring restricted
      lung inflation), effusion volume and impaired diaphragm movement predicted
      Baseline Dyspnoea Index. Un-paired t tests compared the groups with normal and
      impaired diaphragm movement. RESULTS: 19 patients were studied (14 malignant
      etiology). Total lung capacity was associated with Baseline Dyspnoea Index (r =
      0.68, P = 0.003). Effusion volume (r = -0.138, P = 0.60) and diaphragm movement
      (P = 0.09) were not associated with Baseline Dyspnoea Index. Effusion volume was
      larger with impaired diaphragm movement compared to normal diaphragm movement
      (2.16 +/-SD 0.95 vs.1.16 +/-0.92 L, P = 0.009). Total lung capacity was lower
      with impaired diaphragm movement compared to normal diaphragm movement (65.4 +/
      10.3 vs 78.2 +/-8.6% predicted, P = 0.011). The optimal general linear model to
      predict Baseline Dyspnoea Index used total lung capacity alone (adjusted R2 =
      0.42, P = 0.003). In nine participants with controlled effusion, baseline
      effusion volume (r = 0.775, P = 0.014) and total lung capacity (r = -0.690, P =
      0.040) were associated with Transitional Dyspnoea Index. CONCLUSIONS: Restricted
      lung inflation was the principal predictor of increased dyspnoea prior to
      thoracoscopic drainage of effusion, with no independent additional association
      with either effusion volume or impaired ipsilateral diaphragm movement.
      Restricted lung inflation may be an important determinant of the dyspnoea
      associated with pleural effusion.

PMID- 30281614
TI  - Automated tube voltage selection in pediatric non-contrast chest CT.
AB  - BACKGROUND: Modern CT scanners provide automatic dose adjustment systems, which
      are promising options for reducing radiation dose in pediatric CT scans. Their
      impact on patient dose, however, has not been investigated sufficiently thus far.
      OBJECTIVE: To evaluate automated tube voltage selection (ATVS) in combination
      with automated tube current modulation (ATCM) in non-contrast pediatric chest CT,
      with regard to the diagnostic image quality. MATERIALS AND METHODS: There were
      160 non-contrast pediatric chest CT scans (8.7+/-5.4 years) analyzed
      retrospectively without and with ATVS. Correlations of volume CT Dose Index
      (CTDIvol) and effective diameter, with and without ATVS, were compared using
      Fisher's z-transformation. Image quality was assessed by mean signal-difference
      to-noise ratios (SDNR) in the aorta and in the left main bronchus using the
      independent samples t-test. Two pediatric radiologists and a general radiologist
      rated overall subjective Image quality. Readers' agreement was assessed using
      weighted kappa coefficients. A p value <0.05 was considered significant. RESULTS:
      CTDIvol correlation with the effective diameter was r = 0.62 without and r = 0.80
      with ATVS (CI: -0.04 to -0.60; p = 0.025). Mean SDNR was 10.88 without and 10.03
      with ATVS (p = 0.0089). Readers' agreement improved with ATVS (weighted kappa
      between pediatric radiologists from 0.1 (0.03-0.16) to 0.27 (0.09-0.45) with
      ATVS; between general and each pediatric radiologist from 0.1 (0.06-0.14) to 0.12
      (0.05-0.20), and from 0.22 (0.11-0.34) to 0.36 (0.24-0.49)). CONCLUSION: ATVS,
      combined with ATCM, results in a radiation dose reduction for pediatric non
      contrast chest CT without a loss of diagnostic image quality and prevents errors
      in manual tube voltage setting, and thus protecting larger children against an
      unnecessarily high radiation exposure.

PMID- 30281615
TI  - Efficacy and safety of 5 alpha-reductase inhibitor monotherapy in patients with
      benign prostatic hyperplasia: A meta-analysis.
AB  - BACKGROUND: Although combination therapy with 5 alpha-reductase inhibitor (5ARI)
      and alpha-blocker is one of the standard interventions in symptomatic benign
      prostatic hyperplasia (BPH), 5ARI monotherapy is seldom the focus of attention.
      Adverse events associated with 5ARI include depression and suicidal attempts in
      addition to persistent erectile dysfunction. The aim of this study is to update
      our knowledge of clinical efficacy and incidence of adverse events associated
      with 5ARI treatment in symptomatic BPH. METHODS AND FINDINGS: A meta-analysis of
      randomized controlled clinical trials (RCTs) from 1966 until March, 2017 was
      performed using database from PubMed, Cochrane Collaboration and Embase. A total
      of 23395 patients were included in this study and the inclusion criteria were:
      RCTs with 5ARI and placebo in symptomatic BPH patients. Parameters included
      prostate specific antigen (PSA), prostate volume (PV), International Prostate
      Symptom Score (IPPS), post-void residual urine (PVR), voiding symptoms of IPSS
      (voiding IPSS), maximum urinary flow rate (Qmax), and adverse events (AEs). A
      meta-analysis with meta-regression was performed for each effect size and adverse
      events, sensitivity analysis, cumulative analysis along with the analysis of
      ratio of means (ROM) in the placebo group. A total of 42 studies were included in
      this study for review, and a total of 37 studies were included in the meta
      analysis, including a total of 23395 patients (treatment group: 11392, placebo
      group: 12003). The effect size of all variables except PVR showed a significant
      improvement following 5ARI treatment compared with placebo. However, the effect
      size of differences showed declining trend in PV, IPSS and Qmax according to
      recent years of publication. In ROM analysis, PV showed no significant increase
      in the placebo group, with a ROM of 1.00 (95% CI, 0.88, 1.14). The 5ARI treatment
      resulted in a significantly higher incidence of decreased libido (OR = 1.7; 95%
      CI, 1.36, 2.13), ejaculatory disorder (OR = 2.94; 95% CI, 2.15, 4.03),
      gynecomastia (OR = 2.32; 95% CI, 1.41, 3.83), and impotence (OR = 1.74; 95% CI,
      1.32, 2.29). Our study has the following limitations: included studies were
      heterogeneous and direct comparison of efficacy between alpha blocker and 5ARI
      was not performed. Adverse events including depression or suicidal attempt could
      not be analyzed in this meta-analysis setting. CONCLUSIONS: Although there was a
      significant clinical benefit of 5ARI monotherapy compared with placebo, the
      effective size was small. Moreover, the risk of adverse events including sexually
      related complications were high. Additional head-to-head studies are needed to re
      evaluate the clinical efficacy of 5ARI compared with alpha-adrenergic receptor
      blockers.

PMID- 30281616
TI  - HCV seroconversion in a cohort of people who use drugs followed in a mobile harm
      reduction unit in Madrid: Breaking barriers for HCV elimination.
AB  - BACKGROUND AND AIMS: Harm reduction strategies have been shown to decrease the
      incidence of human immunodeficiency virus (HIV) infection in people who inject
      drugs (PWID), but the results have been inconsistent when it comes to prevention
      of hepatitis C virus (HCV) infection. We aimed to examine the rate of HCV
      seroconversion among people who use drugs (PWUD) followed at a mobile harm
      reduction unit (MHRU) to evaluate if a low-threshold methadone substitution
      program (LTMSP) is associated with a low HCV seroconversion rate and subsequently
      identify barriers for elimination. MATERIALS AND METHODS: A cohort of PWUD have
      been followed at a MRHU in Madrid between 2013 and 2016. Individuals who were
      negative for HCV antibodies at baseline and who had at least one retest for HCV
      antibodies were eligible. Kaplan-Meier methods were employed to estimate the
      global incidence density. RESULTS: During the study period, 946 PWUD were
      screened for HCV at least once. At baseline 127 PWUD were negative for HCV
      antibodies and had at least one follow-up HCV antibodies test. The baseline HCV
      prevalence was 33%. After a median 0.89 (IQR 0.3-1.5) years of follow-up and 135
      person-years of risk for HCV infection, 28 subjects seroconverted. The incidence
      density for HCV seroconversion for this sample was 20.7 cases (95% CI: 14.3-29.7)
      per 100 person-years. Injecting drugs in the last year was strongly associated to
      HCV seroconversion (AHR 15.5, 95%CI 4.3-55.8, p < 0.001). Methadone status was
      not associated to HCV seroconversion. CONCLUSIONS: A high incidence of HCV
      infection was found among PWUD at a MHRU in Madrid. In this setting opiate
      substitutive treatment (OST) as a LTMSP does not appear to protect against HCV
      seroconversion.

PMID- 30281617
TI  - Neurodevelopmental disorder-associated ZBTB20 gene variants affect dendritic and
      synaptic structure.
AB  - Dendritic spine morphology and dendritic arborization are key determinants of
      neuronal connectivity and play critical roles in learning, memory and behavior
      function. Recently, defects of ZBTB20, a BTB and zinc finger domain containing
      transcriptional repressor, have been implicated in a wide range of
      neurodevelopmental disorders, including intellectual disability and autism. Here
      we show distinct effects of expression of two major isoforms, long and short, of
      ZBTB20, and its neurodevelopmental disorder-linked variants, on dendritic
      architecture of cultured rat cortical pyramidal neurons. The N-terminal of ZBTB20
      showed a role in regulating dendritic spine morphology. Two ZBTB20 single
      nucleotide variants, located at the N-terminal and central regions of the protein
      and potentially conferring autism risk, altered dendritic spine morphology. In
      contrast, a single nucleotide variant identified in patients with intellectual
      disability and located at the C-terminus of ZBTB20 affected dendritic
      arborization and dendritic length but had no effect on dendritic spine
      morphology. Furthermore, truncation of the extreme C-terminus of ZBTB20 caused
      spine and dendritic morphological changes that were similar but distinct from
      those caused by the C-terminal variant. Taken together, our study suggests
      ZBTB20's role in dendritic and synaptic structure and provide possible mechanisms
      of its effect in neurodevelopmental disorders.

PMID- 30281619
TI  - Antibacterial effects of nano-imprinted moth-eye film in practical settings.
AB  - BACKGROUND: Recent studies report that surfaces displaying micrometer- or
      nanometer-sized undulating structures exhibit antibacterial effects. In previous
      work, we described the use of an advanced nanofabrication technique to generate
      an artificial biomimetic Moth-eye film by coating a polyethylene terephthalate
      (PET) film with nanoscale moth-eye protrusions made from a hydrophilic resin.
      This moth-eye film exhibited enhanced antibacterial effects in in vitro
      experiments. The aim of the present study was to verify the antibacterial
      efficacy of the Moth-eye film in practical environments. MATERIALS AND METHODS:
      The antibacterial effects of three types of film (Moth-eye film, Flat film, and
      PET film) were compared. Sample films were pasted onto hand washing basins at the
      testing locations. After several hours, bacteria were collected from the surface
      of the sample films with one of three kinds of culture media stamper (to permit
      identification of bacterial species). The stampers were incubated for 48 hours at
      35 degrees C, and the numbers of colonies were counted. RESULTS AND DISCUSSION:
      The number of common bacteria including E. coli and S. aureus obtained from the
      Moth-eye film was significantly lower than those from the PET film (p<0.05) and
      Flat film at 1 hour (p<0.05). This study found that the Moth-eye film showed a
      long-term (6h) antibacterial effect and the Moth-eye structure (PET coated with
      nanoscale cone-shaped pillars) demonstrated a physical antibacterial effect from
      earlier time points. Therefore, the Moth-eye film appears to have potential
      general-purpose applications in practical environments.

PMID- 30281620
TI  - A four-stage DEA-based efficiency evaluation of public hospitals in China after
      the implementation of new medical reforms.
AB  - This study applied the non-parametric four-stage data envelopment analysis method
      (Four-Stage DEA) to measure the relative efficiencies of Chinese public hospitals
      from 2010 to 2016, and to determine how efficiencies were affected by eight
      factors. A sample of public hospitals (n = 84) was selected from Chongqing,
      China, including general hospitals and traditional Chinese medicine hospitals
      graded level 2 or above. The Four-Stage-DEA method was chosen since it enables
      the control of the impact of environment factors on efficiency evaluation
      results. Data on the number of staff, government financial subsidies, the number
      of beds and fixed assets were used as input whereas the number of out-patients
      and emergency department patients and visits, the number of discharged patients,
      medical and health service income and hospital bed utilization rate were chosen
      as study outputs. As relevant environmental variables, we selected GDP per
      capita, permanent population, population density, number of hospitals and number
      of available sickbeds in local medical institutions. The relative efficiencies
      (i.e. technical, pure technical, scale) of sample hospitals were also calculated
      to analyze the change between the first stage and fourth stage every year. The
      study found that Four-Stage-DEA can effectively filter the impact of
      environmental factors on evaluation results, which sets it apart from other
      models commonly used in existing studies.

PMID- 30281618
TI  - Prevalence, incidence, predictors, treatment, and control of hypertension among
      HIV-positive adults on antiretroviral treatment in public sector treatment
      programs in South Africa.
AB  - BACKGROUND: One of the key risk factors for cardiovascular disease is
      hypertension. Hypertension, which leads to heart attacks and strokes, already
      affects one billion people worldwide, making it a global public health issue.
      Incidence and prevalence of the condition is on the rise in low- and middle
      income countries, with the biggest increase in sub-Saharan Africa and South
      Africa at the forefront. We examined the prevalence, incidence, predictors,
      treatment, and control of hypertension among HIV-positive patients on ART in a
      large South African observational cohort. METHODS: We conducted a prospective
      study of ART naive adults initiating ART at a public sector HIV clinic in South
      Africa between April 2004-2017. Patients with diagnosed hypertension at ART
      initiation were excluded from the incidence analysis. Log-binomial regression was
      used to estimate predictors of hypertension at ART initiation, while competing
      risks regression was used to evaluate the relationship between predictors of
      incident hypertension, accounting for death as a competing risk. RESULTS: Among
      77,696 eligible patients, 22.0% had prevalent hypertension at ART initiation. Of
      the remaining patients with no hypertension at ART initiation, 8,125 incident
      hypertension cases were diagnosed over the period of follow-up, corresponding to
      an incident rate of 5.4 per 100 person-years (95% confidence interval (CI): 5.3
      5.6). We found patients >=40 years of age and patients with a body mass index
      (BMI) >=25kg/m2 were at increased risk of both prevalent and incident
      hypertension. Male patients and those with pre-hypertension at ART initiation had
      increased hazards of hypertension over the period of follow-up. When assessing
      the choice of antiretroviral drug in first-line ART, patients initiated on
      nevirapine were at 27% increased risk of developing hypertension compared to
      those initiated on efavirenz, while patients who initiated on either zidovudine
      or stavudine had a 40% increased risk of developing hypertension compared to
      patients initiated on tenofovir. Patientswith poorer health status at ART
      initiation (i.e. WHO III/IV stage, low CD4 count, low hemoglobin levels and low
      BMI) had a decrease risk of prevalent hypertension. We found an inverse
      relationship in patients with a CD4 count <50 cells/mm3 at ART initiation who had
      a 25% increased risk of incident hypertension compared to those with a CD4 count
      >=350 cells/mm3. CONCLUSION: Over 20% of patients in our cohort had hypertension
      at ART initiation, and 13% of those with normal blood pressure at ART initiation
      developed hypertension while on ART. Older patients, males, those on nevirapine,
      zidovudine or stavudine, and those who are overweight/obese should be targeted
      for frequent blood pressure monitoring and the identification of other
      cardiovascular risk factors to encourage lifestyle modifications. Additionally,
      these groups should be offered pharmaceutical therapy to help prevent myocardial
      infarction, heart failure, stroke, and kidney disease. Further research is needed
      to determine the level of access and adherence to pharmaceutical treatment for
      hypertension in this population. Additionally, an HIV-negative comparison
      population is needed to assess the association of the HIV virus itself with
      hypertension.

PMID- 30281621
TI  - A cardiac risk score based on sudomotor function to evaluate cardiovascular
      autonomic neuropathy in asymptomatic Chinese patients with diabetes mellitus.
AB  - BACKGROUNDS: Cardiac autonomic neuropathy is a common but always overlooked. More
      convenient diagnostic methods are needed. HYPOTHESIS: Cardiac autonomic
      neuropathy risk score evaluated by SUDOSCAN has a fine diagnostic efficacy
      detecting cardiac autonomic neuropathy. METHODS: This is a cross-sectional study
      among patients with diabetes mellitus. Subjects undertook SUDOSCAN tests and
      cardiac autonomic reflex tests, including heart rate variability due to Valsalva
      maneuver, heart rate response due to deep breathing and heart rate response due
      to standing up. Presenting 2 abnormal results was defined as cardiac autonomic
      neuropathy. RESULTS: Subjects with cardiac autonomic neuropathy has significantly
      higher cardiac autonomic neuropathy risk score (32.88+/-1.60 vs 27.64+/-1.24,P =
      0.010). Cardiac autonomic neuropathy risk score was correlated significantly with
      the heart rate response due to deep breathing(P = 0.004). Multiple regression
      analysis including significant variables showed an independent association of
      cardiac autonomic neuropathy risk score and heart rate response due to deep
      breathing (P = 0.031) and age (P = 0.000). In receiver operating characteristic
      curve analysis evaluating the relationship between cardiac autonomic neuropathy
      risk score and cardiac autonomic neuropathy, The cut-off value was 20.5, with the
      sensitivity of 90.48%, the specificity of 29.5%, and the positive predictive
      value of 46.9%. In two-step diagnostic methods, Setting 20.5 as the cut-off value
      of cardiac autonomic neuropathy risk score and abnormal heart rate response due
      to standing up as the second diagnostic step's positive result, and setting 16.5
      as the cut-off value of cardiac autonomic neuropathy risk score and abnormal
      heart rate response due to deep breathing as the second diagnostic step's
      positive result, both achieved good diagnostic efficacy. CONCLUSION: Cardiac
      autonomic neuropathy risk score evaluated by SUDOSCAN is a good screening test
      for cardiac autonomic neuropathy. The two-step diagnostic methods could be
      considered as surrogate diagnostic methods.

PMID- 30281622
TI  - Searching for answers in an uncertain world: Meaning threats lead to increased
      working memory capacity.
AB  - The Meaning Maintenance Model posits that individuals seek to resolve uncertainty
      by searching for patterns in the environment, yet little is known about how this
      is accomplished. Four studies investigated whether uncertainty has an effect on
      people's cognitive functioning. In particular, we investigated whether meaning
      threats lead to increased working memory capacity. In each study, we exposed
      participants to either an uncertain stimulus used to threaten meaning in past
      studies, or a control stimulus. Participants then completed a working memory
      measure, where they either had to recall lists of words (Studies 1, 2), or
      strings of digits (Studies 3, 4). We used both a frequentist approach and
      Bayesian analysis to evaluate our findings. Across the four studies, we find a
      small but consistent effect, where participants in the meaning threat condition
      show improved performance on the working memory tasks. Overall, our findings were
      consistent with the hypothesis that working memory capacity increases when people
      experience a meaning threat, which may help to explain improved pattern
      recognition. Additionally, our results highlight the value of using a Bayesian
      analytic approach, particularly when studying phenomena with high variance.

PMID- 30281623
TI  - Dental anomalies and lesions in Eastern Atlantic harbor seals, Phoca vitulina
      vitulina (Carnivora, Phocidae), from the German North Sea.
AB  - Skulls of 1,901 Eastern Atlantic harbor seals (Phoca vitulina vitulina) were
      systematically studied for externally visible dental anomalies and lesions. The
      sample comprised 927 males and 974 female individuals, with age at death ranging
      between 1 week and 25 years. Most of the skulls originated from animals collected
      in 1988, when the population suffered from a mass mortality event caused by the
      phocine distemper virus (PDV). Mean age (+/- SD) of females (6.7 +/- 6.4 years)
      was higher (p = 0.002) than that of males (5.9 +/- 5.2 years). In 264
      individuals, one or more teeth were missing either congenitally (n = 26 animals,
      1.4%) or due to intravital loss (n = 238 animals, 12.5%). One male exhibited
      congenital absence of all teeth (anodontia). As this animal had been reported to
      be almost hairless, the condition was tentatively diagnosed as a case of
      hypohidrotic ectodermal dysplasia. Males were more frequently (p = 0.002)
      affected by intravital tooth loss (15.0%) than females (10.2%). Supernumerary
      teeth were found in 3.4% of the skulls, with females (4.7%) showing hyperodontia
      more frequently (p < 0.001) than males (1.9%). Fifty-nine individuals (3.1%; 28
      males, 31 females, p = 0.84) exhibited abnormal tooth morphology. Tooth fractures
      were noted in 40 seals (2.1%), with males being more frequently affected than
      females (p = 0.017). Periapical lesions were diagnosed in 143 skulls, with a
      tendency (p = 0.05) for males (8.7%) to be more frequently affected than females
      (6.4%). Enamel hypoplasia was not observed in the study sample. Analyzing the
      occurrence of dental anomalies and lesions in wild mammals can substantially
      contribute to an assessment of population health and thereby broaden the basis
      for effective species conservation and informed management decisions.

PMID- 30281624
TI  - Decomposition of Ethiopian life expectancy by age and cause of mortality; 1990
      2015.
AB  - Ethiopia's average life expectancy has improved by more than 18 years from 1990
      to 2015. This initiated interest to study the gain in life expectancy with
      respect to age structure and cause of death. Applying a life expectancy
      decomposition technique on secondary data obtained from the Institute of Health
      Metrics and Evaluation, the study found that the burden of disease in Ethiopia
      has declined from 626.18 in 1990 to 225.69 in 2015 per 1000 population measured
      in age-standardized rate of life years lost. The major causes of burden in 1990;
      namely lower respiratory tract infections, neonatal disorders, diarrheal diseases
      and neglected tropical diseases at rates of 89.2, 63.2, 61.2, and 42.2 age
      standardized years of life lost per 1000 population respectively; have shown a
      fast decline in 2015. Deaths from neglected tropical disease showed 94.95%
      reduction, contributing to 5.71(27.30%) years gain in life expectancy followed by
      lower respiratory tract infection and diarrheal disease contributing about 4.65
      years (22.23%) and 1.48 years (7.10%) respectively. On the other hand, about 3.3
      (15.73%) years and 6.4 (30.71%) years of increase in life expectancy are achieved
      through improved longevity in infants and children aged 1-4 years respectively.
      In conclusion, the study found that reductions in under-five child mortality and
      decline in burden of major communicable diseases could explain the major gain in
      life expectancy. However, findings also revealed that the prevalence of non
      communicable diseases and injuries are on the rise calling for the need to be
      addressed by the public health system.

PMID- 30281625
TI  - Evaluation of lung toxicity risk with computed tomography ventilation image for
      thoracic cancer patients.
AB  - BACKGROUND: Four-dimensional computed tomography (4D-CT) ventilation is an
      emerging imaging modality. Functional avoidance of regions according to 4D-CT
      ventilation may reduce lung toxicity after radiation therapy. This study
      evaluated associations between 4D-CT ventilation-based dosimetric parameters and
      clinical outcomes. METHODS: Pre-treatment 4D-CT data were used to retrospectively
      construct ventilation images for 40 thoracic cancer patients retrospectively.
      Fifteen patients were treated with conventional radiation therapy, 6 patients
      with hyperfractionated radiation therapy and 19 patients with stereotactic body
      radiation therapy (SBRT). Ventilation images were calculated from 4D-CT data
      using a deformable image registration and Jacobian-based algorithm. Each
      ventilation map was normalized by converting it to percentile images. Ventilation
      based dosimetric parameters (Mean Dose, V5 [percent lung volume receiving >=5
      Gy], and V20 [percent lung volume receiving >=20 Gy]) were calculated for highly
      and poorly ventilated regions. To test whether the ventilation-based dosimetric
      parameters could be used predict radiation pneumonitis of >=Grade 2, the area
      under the curve (AUC) was determined from the receiver operating characteristic
      analysis. RESULTS: For Mean Dose, poorly ventilated lung regions in the 0-30%
      range showed the highest AUC value (0.809; 95% confidence interval [CI], 0.663
      0.955). For V20, poorly ventilated lung regions in the 0-20% range had the
      highest AUC value (0.774; 95% [CI], 0.598-0.915), and for V5, poorly ventilated
      lung regions in the 0-30% range had the highest AUC value (0.843; 95% [CI], 0.732
      0.954). The highest AUC values for Mean Dose, V20, and V5 were obtained in poorly
      ventilated regions. There were significant differences in all dosimetric
      parameters between radiation pneumonitis of Grade 1 and Grade >=2. CONCLUSIONS:
      Poorly ventilated lung regions identified on 4D-CT had higher AUC values than
      highly ventilated regions, suggesting that functional planning based on poorly
      ventilated regions may reduce the risk of lung toxicity in radiation therapy.

PMID- 30281627
TI  - The struggle for existence in the world market ecosystem.
AB  - The global trade system can be viewed as a dynamic ecosystem in which exporters
      struggle for resources: the markets in which they export. We can think that the
      aim of an exporter is to gain the entirety of a market share (say, car imports
      from the United States). This is similar to the objective of an organism in its
      attempt to monopolize a given subset of resources in an ecosystem. In this paper,
      we adopt a multilayer network approach to describe this struggle. We use
      longitudinal, multiplex data on trade relations, spanning several decades. We
      connect two countries with a directed link if the source country's appearance in
      a market correlates with the target country's disappearing, where a market is
      defined as a country-product combination in a given decade. Each market is a
      layer in the network. We show that, by analyzing the countries' network roles in
      each layer, we are able to classify them as out-competing, transitioning or
      displaced. This classification is a meaningful one: when testing the future
      export patterns of these countries, we show that out-competing countries have
      distinctly stronger growth rates than the other two classes.

PMID- 30281628
TI  - Elevated empathy in adults following childhood trauma.
AB  - Traumatic events increase the risk of depression, but there is also evidence that
      adversity can lead to posttraumatic growth, including increased compassion and
      prosocial behavior. To date there is no empirical research pinpointing childhood
      trauma to an increase in trait empathy in adulthood. Although somewhat counter
      intuitive, this might be predicted if trauma not only increases fear of future
      threat but also renders the individual more sensitive to suffering in others. We
      explored this possible link using multiple studies, self-report measures, and non
      clinical samples. Results across samples and measures showed that, on average,
      adults who reported experiencing a traumatic event in childhood had elevated
      empathy levels compared to adults who did not experience a traumatic event.
      Further, the severity of the trauma correlated positively with various components
      of empathy. These findings suggest that the experience of a childhood trauma
      increases a person's ability to take the perspective of another and to understand
      their mental and emotional states, and that this impact is long-standing. Future
      research needs to test if this is seen on performance measures, and how these
      findings extend to clinical populations.

PMID- 30281626
TI  - Systemic treatment with resveratrol reduces the progression of experimental
      periodontitis and arthritis in rats.
AB  - Rheumatoid arthritis and periodontitis are chronic inflammatory diseases which
      has been closely associated due to the nature of immune-inflammatory imbalance
      response. Resveratrol is a naturall product with biological proprieties that may
      promote immunomodulatory effects on host response. This study investigated
      resveratrol continuous administration effect on experimental periodontitis and
      arthritis progression in rats. Thirty-five rats were assigned to the following
      groups: 1-experimental arthritis + experimental periodontitis + placebo (RA+EP
      +PL) (n = 12); 2 -RA+EP+ ibuprofen (RA+PE+IB) (n = 11); 3-RA+EP+ resveratrol
      (RA+PE+RSV) (n = 11). After euthanasia, the specimens were processed for
      morphometric analysis of bone loss, and the gingival tissue surrounding the first
      molar was collected for quantification of inflammatory markers using a
      Luminex/MAGpix assay and anti-citrullinated protein antibody (ACCPA) levels were
      measured by ELISA assay. Serum level of rheumatoid factor (RF) was measured by
      ELISA assay. Paw edema was analyzed using a plethysmometer. Higher bone loss was
      observed in PL group, when compared to IB and RSV groups. RSV group presented
      higher IL-4 concentration than PL and IB groups. Resveratrol reduced RF serum
      levels and both IB and RSV decreased ACCPA gingival levels. Besides, paw swelling
      level was significantly lower in IB and RSV groups in the 21th day and only in
      RSV group in the 28th day. Histological analyzes showed smooth articular surface
      and higher width of the subchondral cortical in RSV group. Resveratrol showed
      modulatory effect and seems to reduce the inflammatory signs of arthritis and
      articular damage throughout the time.

PMID- 30281629
TI  - What you saw is what you will hear: Two new illusions with audiovisual
      postdictive effects.
AB  - Neuroscience investigations are most often focused on the prediction of future
      perception or decisions based on prior brain states or stimulus presentations.
      However, the brain can also process information retroactively, such that later
      stimuli impact conscious percepts of the stimuli that have already occurred
      (called "postdiction"). Postdictive effects have thus far been mostly unimodal
      (such as apparent motion), and the models for postdiction have accordingly been
      limited to early sensory regions of one modality. We have discovered two related
      multimodal illusions in which audition instigates postdictive changes in visual
      perception. In the first illusion (called the "Illusory Audiovisual Rabbit"), the
      location of an illusory flash is influenced by an auditory beep-flash pair that
      follows the perceived illusory flash. In the second illusion (called the
      "Invisible Audiovisual Rabbit"), a beep-flash pair following a real flash
      suppresses the perception of the earlier flash. Thus, we showed experimentally
      that these two effects are influenced significantly by postdiction. The
      audiovisual rabbit illusions indicate that postdiction can bridge the senses,
      uncovering a relatively-neglected yet critical type of neural processing
      underlying perceptual awareness. Furthermore, these two new illusions broaden the
      Double Flash Illusion, in which a single real flash is doubled by two sounds.
      Whereas the double flash indicated that audition can create an illusory flash,
      these rabbit illusions expand audition's influence on vision to the suppression
      of a real flash and the relocation of an illusory flash. These new additions to
      auditory-visual interactions indicate a spatio-temporally fine-tuned coupling of
      the senses to generate perception.

PMID- 30281630
TI  - Barking mad: The vocalisation of the John Dory, Zeus faber.
AB  - Studies on the behavioural function of sounds are very rare within heterospecific
      interactions. John Dory (Zeus faber) is a solitary, predatory fish that produces
      sound when captured, but has not been documented to vocalize under natural
      conditions (i.e. in the wild). The present study provides the first in-situ
      recordings of John Dory vocalisations and correlates them to behavioural response
      of snapper (Pagrus auratus) a common species found through New Zealand.
      Vocalisations or 'barks', ranged between 200-600 Hz, with a peak frequency of 312
      +/- 10 Hz and averaged 139 +/- 4 milliseconds in length. Baited underwater video
      (BUV) equipped with hydrophones determined that under natural conditions a John
      Dory vocalization induced an escape response in snapper present, causing them to
      exit the area opposite to the position of the John Dory. We speculate that the
      John Dory vocalisation may be used for territorial display towards both
      conspecifics and heterospecifics, asserting dominance in the area or heightening
      predatory status.

PMID- 30281631
TI  - The twin epidemics: Prevalence of TB/HIV co-infection and its associated factors
      in Ethiopia; A systematic review and meta-analysis.
AB  - BACKGROUND: Tuberculosis and HIV/AIDS are the major public health problems in
      many parts of the world particularly in resource limited countries like Ethiopia.
      Although studies have been conducted on the prevalence and associated factors of
      TB / HIV co-infection in Ethiopia, there is no comprehensive data on the
      magnitude and risk factors at a national and regional levels. Therefore, this
      review is aimed to summarize the prevalence of TB /HIV co-infection in Ethiopia
      using meta-analysis based on a systematic review of published articles & grey
      literatures. METHODS: To conduct this systematic review and meta-analysis, major
      databases such as Pub Med, Google scholar, CINAHL, Africa Journals Online and
      Google were systematically searched using search terms. PRISMA guideline was
      followed in the study. Two authors extracted all necessary data using a
      standardized data extraction format, and analysis was done using STATA version
      11. A Statistical heterogeneity across the studies was evaluated by using
      Cochran's Q test and I2 statistic. The pooled effect size was conducted in the
      form of prevalence and associations were measured using odds ratio. Moreover, the
      univariate meta regression was performed by considering the sample size to
      determine potential sources of heterogeneity. The Egger's weighted regression and
      Begg's rank correlation tests were used to assess potential publication biases.
      RESULTS: This meta-analysis included 21 studies with a total of 12,980
      participants. The pooled prevalence of TB / HIV Co-infection was 25.59% (95% CI
      (20.89%-30.29%). A significant association was found between low CD4 counts (OR:
      3.53; 95% CI: 1.55, 8.06), advanced WHO stage (OR: 6.81; 95% CI: 3.91, 11.88) and
      TB/ HIV/AIDS Co-infection. CONCLUSION: This finding revealed that the magnitude
      of TB /HIV co-infection in Ethiopia is increasing and deserves special attention.
      Low CD4 count and advanced WHO stage are contributing factors for dual infection.
      Establishing mechanisms such as Conducting surveillance to determine HIV burden
      among TB patients and TB burden among HIV patients, and intensifying the three
      I's (Intensive case finding, INH Preventive Therapy and Infection control) should
      be routine work of clinicians. Moreover, early screening & treatment should be
      provided to those patients with low CD4 count and advanced WHO stage.

PMID- 30281632
TI  - Physiological, perceptual, and technical responses to continuous and intermittent
      small-sided games in lacrosse players.
AB  - PURPOSE: The present study was designed to investigate the influence of two
      distinct small-sided game (SSG) regimes on physiological, perceptual, and
      technical parameters in male elite lacrosse players. METHOD: Data were collected
      in twelve elite male Austrian lacrosse players (25.8 +/- 5.5 years; 80.1 +/- 7.7
      kg; 178.5 +/- 6.2 cm). Players' were assigned to an intermittent (SSG-I) or a
      continuous (SSG-C) SSG regime, respectively. Regimes were equated for total
      practice time, but not active playing time. SSG data from eight sessions of 3 vs.
      3 self-regulated match-play were collected along a 4-week pre-season period.
      Players' YoYo-Level 1 (YYL1) performance before and after the training
      intervention was recorded. Further, heart-rate (HR), rating of perceived exertion
      (RPE), physical activity enjoyment scale (PACES), and technical actions during
      and after SSG sessions were analyzed. RESULTS: Both SSG regimes showed
      improvement with medium to very large effect sizes (ES) in YYL1 total distance
      covered pre- to post-intervention (SSG-C mean-difference +/- SD: 840 +/- 299 m; p
      = 0.003; d = 1.08; CI = 0.60 to 1.56 and SSG-I: 607 +/- 274 m; p = 0.003; d =
      1.25; CI = 0.66 to 1.85 respectively). Higher %HRmax values with very large ES
      (92 +/- 0.6%; p = 0.002; d = 5.33; CI = 2.78 to 7.88) and time spent in HR zone 4
      (1248.0 +/- 122.7 s; p = 0.000; d = 3.43; CI = 2.31 to 4.55) were observed for
      SSG-C. No differences between regimes were found for any of the assessed
      technical actions, global RPE, and PACES scores. CONCLUSIONS: Both SSG regimes
      investigated in this study were effective in improving YYL1 performance. Further,
      findings indicate that the regime does not influence players' subjective feelings
      and technical actions in SSG play. However, SSG-I in lacrosse specific training
      could have additional benefits such as lower signs of fatigue. Further, breaks
      can be used to give technical and tactical inputs by coaches.

PMID- 30281633
TI  - Detection and serotyping of dengue viruses in febrile patients consulting at the
      New-Bell District Hospital in Douala, Cameroon.
AB  - Arboviruses are a major public health problem worldwide and are predominantly
      present in intertropical areas. Chikungunya, dengue and zika viruses have been
      implicated in recent epidemics in Asia, America and Africa. In Cameroon, data on
      these viruses are fragmentary. The purpose of this study was to determine the
      frequency of detection of these three viruses in febrile patients in Douala,
      Cameroon. A cross-sectional and descriptive study was conducted from March to
      April 2017 at the New-Bell District Hospital in Douala. Blood samples were
      collected from febrile patients and tested for malaria infections using Rapid
      Diagnostic test. Plasma harvested was later analyzed for the presence of
      chikungunya, dengue and zika viruses by a Trioplex real-time RT-PCR at Centre
      Pasteur of Cameroon. A total of 114 participants were included, of which 63.2%
      were females, reflecting a sex ratio (female/male) of 1.7. The median age was 26
      years, range [0.25-81]. Eight (7%) of the 114 participants were infected with
      Dengue virus (DENV) among which 5 were identified as serotype 1. No cases of
      infection by either Zika virus or Chikungunya virus were detected. Three cases of
      dengue-malaria co-infection (13%) were recorded. No association was found between
      socio-demographic factors and dengue infection. The phylogenetic analysis of the
      partial envelope E gene showed that all the five DENV serotype 1 samples belonged
      to subtype V, similarly to strains from West African countries, particularly
      those from Nigeria, Senegal and Cote d'Ivoire. This study showed the circulation
      of DENV serotype 1 in febrile patients and raises the alarm for the establishment
      of a sustained surveillance system to detect cases and prevent potential
      outbreaks in Cameroon. The existence of dengue-malaria co-infections suggests
      that surveillance of arboviruses should not be limited to febrile, non-malarial
      cases.

PMID- 30281634
TI  - Dominant malaria vector species in Nigeria: Modelling potential distribution of
      Anopheles gambiae sensu lato and its siblings with MaxEnt.
AB  - Malaria is a major infectious disease that still affects nearly half of the
      world's population. Information on spatial distribution of malaria vector species
      is needed to improve malaria control efforts. In this study we used Maximum
      Entropy Model (MaxEnt) to estimate the potential distribution of Anopheles
      gambiae sensu lato and its siblings: Anopheles gambiae sensu stricto, and
      Anopheles arabiensis in Nigeria. Species occurrence data collected during the
      period 1900-2010 was used together with 19 bioclimatic, landuse and terrain
      variables. Results show that these species are currently widespread across all
      ecological zones. Temperature fluctuation from mean diurnal temperature range,
      extreme temperature and precipitation conditions, high humidity in dry season
      from precipitation during warm months, and land use and land cover dynamics have
      the greatest influence on the current seasonal distribution of the Anopheles
      species. MaxEnt performed statistically significantly better than random with AUC
      approximately 0.7 for estimation of the Anopheles species environmental
      suitability, distribution and variable importance. This model result can
      contribute to surveillance efforts and control strategies for malaria
      eradication.

PMID- 30281635
TI  - The body inversion effect in chimpanzees (Pan troglodytes).
AB  - Bodies are important social cues for animals. Body recognition in humans is
      deteriorated by inversion. This inversion effect suggests the configural
      processing of bodies, which is different from the processing used for other
      objects. However, it is not known if this type of body processing exists in non
      human primates. We tested seven chimpanzees using upright and inverted chimpanzee
      body stimuli and other stimuli in matching-to-sample tasks to examine the body
      inversion effect and the body parts that invoke it. Our results reflected the
      body inversion effect for intact chimpanzee bodies, bodies with complete body
      contours, and bodies with clear faces but not for the objects and other
      conditions that did not present complete body contours and clear faces. The
      results show that chimpanzees share configural body processing with humans and
      that bodies are special to them compared with other objects. The results also
      revealed the functions of faces and body contours in configural processing by
      chimpanzees.

PMID- 30281637
TI  - Correction: Implications of the Ebola virus disease outbreak in Guinea:
      Qualitative findings to inform future health and nutrition-related responses.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0202468.].

PMID- 30281636
TI  - A response surface optimization approach to adjust ionic current conductances of
      cardiac electrophysiological models. Application to the study of potassium level
      changes.
AB  - Cardiac electrophysiological computational models are often developed from
      previously published models. The new models may incorporate additional features
      to adapt the model to a different species or may upgrade a specific ionic
      formulation based on newly available experimental data. A relevant challenge in
      the development of a new model is the estimation of certain ionic current
      conductances that cannot be reliably identified from experiments. A common
      strategy to estimate those conductances is by means of constrained non-linear
      least-squares optimization. In this work, a novel methodology is proposed for
      estimation of ionic current conductances of cardiac electrophysiological models
      by using a response surface approximation-based constrained optimization with
      trust region management. Polynomial response surfaces of a number of
      electrophysiological markers were built using statistical sampling methods. These
      markers included action potential duration (APD), triangulation, diastolic and
      systolic intracellular calcium concentration, and time constants of APD rate
      adaptation. The proposed methodology was applied to update the Carro et al. human
      ventricular action potential model after incorporation of intracellular potassium
      ([K+]i) dynamics. While the Carro et al. model was well suited for investigation
      of arrhythmogenesis, it did not allow simulation of [K+]i changes. With the
      methodology proposed in this study, the updated Carro et al. human ventricular
      model could be used to simulate [K+]i changes in response to varying
      extracellular potassium ([K+]o) levels. Additionally, it rendered values of
      evaluated electrophysiological markers within physiologically plausible ranges.
      The optimal values of ionic current conductances in the updated model were found
      in a notably shorter time than with previously proposed methodologies. As a
      conclusion, the response surface optimization-based approach proposed in this
      study allows estimating ionic current conductances of cardiac
      electrophysiological computational models while guaranteeing replication of key
      electrophysiological features and with an important reduction in computational
      cost with respect to previously published approaches. The updated Carro et al.
      model developed in this study is thus suitable for the investigation of
      arrhythmic risk-related conditions, including those involving large changes in
      potassium concentration.

PMID- 30281639
TI  - Dead and buried? Variation in post-mortem histories revealed through
      histotaphonomic characterisation of human bone from megalithic graves in Sweden.
AB  - This study investigates possible variation in post-mortem histories during the
      Neolithic period in southwestern Sweden based on microscopic studies of human
      bone. Numerous megalithic graves were built in this region and good preservation
      conditions have left a rich skeletal record. After more than a hundred years of
      research, it is still a controversy whether or not these skeletal assemblages
      were the result of primary burials, or ossuaries where skeletonized remains were
      deposited. In this study we apply histological analysis to obtain insights into
      post-mortem histories and taphonomic processes affecting the human remains,
      potentially including funerary rituals. This type of analysis records the
      condition and traces of degradation found in skeletal material at a microscopic
      level. Human skeletal material from four different megalithic tombs in the
      Falbygden area has been sampled and analysed by thin-section light microscopy,
      and by scanning electron microscopy. The results of the study provide evidence of
      variation and changes in burial conditions for skeletal remains from the
      different graves, also for remains from the same grave. Extent of bioerosion
      varied, from extensive to moderate/arrested, to none. Bone samples from the same
      graves also differed in the type of staining and mineral inclusions, showing that
      the non-bioeroded samples relatively early post-mortem must have experienced an
      anoxic environment, and later a change to an aerated environment. This could be
      taken as an indication of primary burial somewhere else, but more likely reflect
      a special micro-environment occurring temporarily in some graves and parts of
      graves after the tombs were filled with soil and sealed by roof slabs. The study
      illustrates the usefulness of bone histological analysis in the reconstruction of
      post-mortem histories, revealing variations not discernible at macro-level that
      may aid in the interpretations of funerary rituals. However, the results also
      highlight the issues of equifinality. Based on current data and knowledge,
      several scenarios are possible. Further histotaphonomic work is advisable,
      including archaeological remains from megalithic tombs, and bones from taphonomic
      experiments.

PMID- 30281638
TI  - Prevalence of childhood obstructive sleep apnea syndrome and its role in daytime
      sleepiness.
AB  - OBJECTIVES: To investigate childhood obstructive sleep apnea syndrome (OSAS) and
      its role in daytime sleepiness among school-age children. METHODS: A
      questionnaire survey was conducted with 25,211 children aged 6-15 (mean, 10.39)
      years attending 148 elementary and 71 middle schools in 10 prefectures across
      Japan and their parents. Questions concerned 4 sleep habit items (bedtime, sleep
      onset latency, wake time after sleep onset, wake-up time) and 4 sleep disorder
      items (loud snoring, snorts/gasps, breathing pauses, seems very sleepy in the
      daytime). Total sleep time (TST) was calculated with sleep habits. Severe
      possible OSAS (p-OSAS) was defined as having loud snoring, snorts and gasps, or
      breathing pauses "frequently" (>= 5 times per week), and mild p-OSAS was rated as
      having any of these "sometimes" (2-4 times per week). Severe daytime sleepiness
      was defined as seeming very sleepy "frequently" and mild daytime sleepiness as
      seeming very sleepy "sometimes". RESULTS: Mean prevalence of mild to severe p
      OSAS and severe p-OSAS in children across all grade levels was 9.5% and 1.6%,
      respectively. p-OSAS was particularly prevalent in children at lower elementary
      levels, decreasing with advancing grade levels. Prevalence of mild and severe
      daytime sleepiness was 6.1% and 0.9%, respectively, among all children (7.0%).
      Prevalence of daytime sleepiness increased with advancing grade levels,
      particularly in middle-school level. Average TST was 8.4 +/- 2.2 h in both
      elementary and middle-school levels, and decreased as grades advanced,
      particularly in middle-school levels. Multivariate logistic regression analysis
      showed that middle-school level, TST < 8 h, and p-OSAS were independent factors
      for daytime sleepiness. Strong correlations were found between severe daytime
      sleepiness and severe p-OSAS or TST < 6 h, and between daytime sleepiness and
      loud snoring or breathing pauses. CONCLUSION: p-OSAS may be an independent factor
      influencing daytime sleepiness in school-age children. Loud snoring and breathing
      pauses could be clinical markers for children with severe daytime sleepiness.

PMID- 30281640
TI  - Correction: Opposing Effects of PI3K/Akt and Smad-Dependent Signaling Pathways in
      NAG-1-Induced Glioblastoma Cell Apoptosis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0096283.].

PMID- 30281641
TI  - Systemic inflammation and eye diseases. The Beijing Eye Study.
AB  - PURPOSE: Systemic inflammation is potentially associated with ocular diseases
      such as late age-related macular degeneration (AMD). Using the serum
      concentration of high-sensitive C-reactive protein (hs-CRP) as surrogate of
      systemic inflammation, we examined potential associations between the serum hs
      CRP concentration and the presence and degree of eye diseases. METHODS: The
      population-based Beijing Eye Study included 3468 Chinese individuals. The study
      participants underwent a standardized interview and a detailed ophthalmic
      examination. The serum concentration of hs-CRP was determined. RESULTS: Out of
      3468 participants, 2452 (70.7%) individuals (mean age:63.4+/-9.4 year; range:50
      91 years) had hs-CRP measurements (mean:1.96+/-4.07mg/L). In multivariate
      analysis, higher serum concentration of hs-CRP was significantly (regression
      coefficient r: 0.21) associated with a higher level of diabetic retinopathy (P =
      0.007; standardized regression coefficient beta:0.06; non-standardized regression
      coefficient B:1.35; 95% confidence interval (CI):0.37,2.22) and polypoidal
      choroidal vasculopathy (P = 0.002;beta:0.06;B:6.22;95%CI:2.24,10.2) after
      adjusting for higher serum concentration of high-density lipoproteins
      (P<0.001;beta:-0.12;B:-1.31;95%CI:-1.77,-0.85), higher body mass index (P =
      0.01;beta:0.06;B:0.06;95%CI:0.01, 0.11), lower level of education (P = 0.04;beta:
      0.06;B:-0.22;95%CI:-0.42,-0.02), lower cognitive function score (P = 0.01;beta:
      0.07;B:-0.08;95%CI:-0.13,-0.02). If the presences of other ocular diseases were
      added to the model, the presence of glaucoma (P = 0.99), open-angle glaucoma (P =
      0.80), angle-closure glaucoma (P = 0.67), pseudoexfoliation (P = 0.18), nuclear
      cataract (P = 0.30), cortical cataract (P = 0.15), subcapsular cataract (P =
      0.59), retinal vein occlusions (P = 0.33), central serous choroidopathy (P =
      0.44), early stage of age-related macular degeneration (AMD) (P = 0.46),
      intermediate stage of AMD (P = 0.20) and late stage of AMD (P = 0.91) including
      geographic atrophy (P = 0.60) or neovascular AMD (P = 0.68) were not
      significantly associated with the serum concentration of hs-CRP. CONCLUSIONS: In
      Chinese aged 50+ years, higher serum concentration of hs-CRP was significantly
      associated with a higher level of diabetic retinopathy and higher frequency of
      polypoidal choroidal vasculopathy. Other major ocular disorders, namely glaucoma
      including open-angle glaucoma and angle-closure glaucoma, pseudoexfoliation,
      nuclear, cortical or subcapsular cataract, retinal vein occlusions, central
      serous choroidopathy, early, intermediate or late stage of AMD including
      geographic atrophy, were not significantly associated with hs-CRP serum
      concentrations. It suggests that these diseases, in contrast to diabetic
      retinopathy and polypoidal choroidal vasculopathy, were not associated with a
      major systemic inflammatory component.

PMID- 30281642
TI  - Harman and norharman, metabolites of entomopathogenic fungus Conidiobolus
      coronatus (Entomopthorales), disorganize development of Galleria mellonella
      (Lepidoptera) and affect serotonin-regulating enzymes.
AB  - Naturally occurring entomopathogenic fungi such as Conidiobolus coronatus are
      important regulatory factors of insect populations. GC-MS analysis of fungal cell
      free filtrates showed that C. coronatus synthesizes two beta- carboline
      alkaloids: harman and norharman. Significantly higher levels of both alkaloids
      are produced by C. coronatus in minimal postincubation medium than in rich
      medium. The beta-carboline alkaloids may have an effect on the nervous system of
      insects and their behavior. Harman and norharman were applied to Galleria
      mellonella larvae (a parasite of honeybees) either topically or mixed with food.
      Larvae received alkaloids in three concentrations: 750, 1000 or 1250 ppm. The
      effect on the survival and further development of larvae was examined. Both
      harman and norharman delayed pupation and adult eclosion, and inhibit total
      monoamine oxidase activity. In addition, they increased the serotonin
      concentration and decreased the monoamine oxidase A level in the heads of the
      moths. It is likely that the alkaloids were metabolized by the insects, as their
      effect wore off 24 hours after topical application. This is the first study to
      show that C. coronatus produces alkaloids. Its aim was to identify the actions of
      beta-carboline alkaloids on insect development and serotonin-regulating enzymes.
      Knowledge of the potential role of harman and norharman in the process of fungal
      infection might lead to the development of more effective and environmentally
      friendly means of controlling insect pests.

PMID- 30281643
TI  - The acute medical unit model: A characterisation based upon the National Health
      Service in Scotland.
AB  - BACKGROUND: Acute medical units (AMUs) receive the majority of acute medical
      patients presenting to hospital as an emergency in the United Kingdom (UK) and in
      other international settings. They have emerged as a result of local service
      innovation in the context of a limited evidence base. As such, the AMU model is
      not well characterised in terms of its boundaries, patient populations and
      components of care. This makes service optimisation and development through
      strategic resource planning, quality improvement and research challenging. AIM:
      This study aims to evaluate a national set of AMUs with the intent of
      characterising the AMU model. METHODS: Twenty-nine AMUs in Scotland were
      identified. Data were collected by semi-structured interviews with
      multidisciplinary healthcare professionals working in each AMU. A draft report
      was produced for each unit and verified by a unit representative. The unit
      reports were then analysed to develop a conceptual framework of key components of
      AMUs and a service definition of the boundaries of acute medical care. RESULTS:
      Acute medical care in Scotland can be described as being delivered in "acute
      medical services" rather than geographically distinct AMUs. Twelve key components
      of AMU care were identified: care areas, functions, populations, patient flow,
      support services, communication, nurse care, allied healthcare professional care,
      non-consultant medical care, consultant care, patient assessment and specialty
      care. DISCUSSION: This empirically derived characterisation of the AMU model is
      likely to be of utility to practitioners, managers, policy makers and
      researchers: it is relevant on an operational level, will aid quality improvement
      and is a foundation to needed further research into how best to deliver care in
      AMUs. This is important given the central role AMUs play in the journey of the
      majority of patients presenting to hospital acutely in Scotland, the UK and
      internationally.

PMID- 30281644
TI  - Predictive models for charitable giving using machine learning techniques.
AB  - Private giving represents more than three fourths of all U.S. charitable
      donations, about 2% of total Gross Domestic Product (GDP). Private giving is a
      significant factor in funding the nonprofit sector of the U.S. economy, which
      accounts for more than 10% of total GDP. Despite the abundance of data available
      through tax forms and other sources, it is unclear which factors influence
      private donation, and a reliable predictive mechanism remains elusive. This study
      aims to develop predictive models to accurately estimate future charitable giving
      based on a set of potentially influential factors. We have selected several
      factors, including unemployment rate, household income, poverty level,
      population, sex, age, ethnicity, education level, and number of vehicles per
      household. This study sheds light on the relationship between donation and these
      variables. We use Stepwise Regression to identify the most influential variables
      among the available variables, based on which predictive models are developed.
      Multiple Linear Regression (MLR) and machine learning techniques, including
      Artificial Neural Networks (ANN) and Support Vector Regression (SVR) are used to
      develop the predictive models. The results suggest that population, education
      level, and the amount of charitable giving in the previous year are the most
      significant, independent variables. We propose three predictive models (MLR, ANN,
      and SVR) and validate them using 10-fold cross-validation method, then evaluate
      the performance using 9 different measuring criteria. All three models are
      capable of predicting the amount of future donations in a given region with good
      accuracy. Based on the evaluation criteria, using a test data set, ANN
      outperforms SVR and MLR in predicting the amount of charitable giving in the
      following year.

PMID- 30281645
TI  - Validation of a genetic risk score for Arkansas women of color.
AB  - African American women in the state of Arkansas have high breast cancer mortality
      rates. Breast cancer risk assessment tools developed for African American
      underestimate breast cancer risk. Combining African American breast cancer
      associated single-nucleotide polymorphisms (SNPs) into breast cancer risk
      algorithms may improve individualized estimates of a woman's risk of developing
      breast cancer and enable improved recommendation of screening and chemoprevention
      for women at high risk. The goal of this study was to confirm with an independent
      dataset consisting of Arkansas women of color, whether a genetic risk score
      derived from common breast cancer susceptibility SNPs can be combined with a
      clinical risk estimate provided by the Breast Cancer Risk Assessment Tool (BCRAT)
      to produce a more accurate individualized breast cancer risk estimate. A
      population-based cohort of African American women representative of Arkansas
      consisted of 319 cases and 559 controls for this study. Five-year and lifetime
      risks from the BCRAT were measured and combined with a risk score based on 75
      independent susceptibility SNPs in African American women. We used the odds ratio
      (OR) per adjusted standard deviation to evaluate the improvement in risk
      estimates produced by combining the polygenic risk score (PRS) with 5-year and
      lifetime risk scores estimated using BCRAT. For 5-year risk OR per standard
      deviation increased from 1.84 to 2.08 with the addition of the polygenic risk
      score and from 1.79 to 2.07 for the lifetime risk score. Reclassification
      analysis indicated that 13% of cases had their 5-year risk increased above the
      1.66% guideline threshold (NRI = 0.020 (95% CI -0.040, 0.080)) and 6.3% of cases
      had their lifetime risk increased above the 20% guideline threshold by the
      addition of the polygenic risk score (NRI = 0.034 (95% CI 0.000, 0.070)). Our
      data confirmed that discriminatory accuracy of BCRAT is improved for African
      American women in Arkansas with the inclusion of specific SNP breast cancer risk
      alleles.

PMID- 30281646
TI  - Loss of Ccbe1 affects cardiac-specification and cardiomyocyte differentiation in
      mouse embryonic stem cells.
AB  - Understanding the molecular pathways regulating cardiogenesis is crucial for the
      early diagnosis of heart diseases and improvement of cardiovascular disease.
      During normal mammalian cardiac development, collagen and calcium-binding EGF
      domain-1 (Ccbe1) is expressed in the first and second heart field progenitors as
      well as in the proepicardium, but its role in early cardiac commitment remains
      unknown. Here we demonstrate that during mouse embryonic stem cell (ESC)
      differentiation Ccbe1 is upregulated upon emergence of Isl1- and Nkx2.5- positive
      cardiac progenitors. Ccbe1 is markedly enriched in Isl1-positive cardiac
      progenitors isolated from ESCs differentiating in vitro or embryonic hearts
      developing in vivo. Disruption of Ccbe1 activity by shRNA knockdown or blockade
      with a neutralizing antibody results in impaired differentiation of embryonic
      stem cells along the cardiac mesoderm lineage resulting in a decreased expression
      of mature cardiomyocyte markers. In addition, knockdown of Ccbe1 leads to smaller
      embryoid bodies. Collectively, our results show that CCBE1 is essential for the
      commitment of cardiac mesoderm and consequently, for the formation of cardiac
      myocytes in differentiating mouse ESCs.

PMID- 30281649
TI  - Correction: Global land use implications of dietary trends.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0200781.].

PMID- 30281647
TI  - Chronic oral application of a periodontal pathogen results in brain inflammation,
      neurodegeneration and amyloid beta production in wild type mice.
AB  - BACKGROUND: The results from cross sectional and longitudinal studies show that
      periodontitis is closely associated with cognitive impairment (CI) and Alzhemer's
      Disease (AD). Further, studies using animal model of periodontitis and human post
      mortem brain tissues from subjects with AD strongly suggest that a gram-negative
      periodontal pathogen, Porphyromonas gingivalis (Pg) and/or its product gingipain
      is/are translocated to the brain. However, neuropathology resulting from Pg oral
      application is not known. In this work, we tested the hypothesis that repeated
      exposure of wild type C57BL/6 mice to orally administered Pg results in
      neuroinflammation, neurodegeneration, microgliosis, astrogliosis and formation of
      intra- and extracellular amyloid plaque and neurofibrillary tangles (NFTs) which
      are pathognomonic signs of AD. METHODS: Experimental chronic periodontitis was
      induced in ten wild type 8-week old C57BL/6 WT mice by repeated oral application
      (MWF/week) of Pg/gingipain for 22 weeks (experimental group). Another 10 wild
      type 8-week old C57BL/6 mice received vehicle alone (control group) MWF per week
      for 22 weeks. Brain tissues were collected and the presence of Pg/gingipain was
      determined by immunofluorescence (IF) microscopy, confocal microscopy, and
      quantitative PCR (qPCR). The hippocampi were examined for the signs of
      neuropathology related to AD: TNFalpha, IL1beta, and IL6 expression
      (neuroinflammation), NeuN and Fluoro Jade C staining (neurodegeneration) and
      amyloid beta1-42 (Abeta42) production and phosphorylation of tau protein at
      Ser396 were assessed by IF and confocal microscopy. Further, gene expression of
      amyloid precursor protein (APP), beta-site APP cleaving enzyme 1 (BACE1), a
      disintegrin and metalloproteinase domain-containing protein10 (ADAM10) for alpha
      secretase and presenilin1 (PSEN1) for gamma-secretase, and NeuN (rbFox3) were
      determined by RT-qPCR. Microgliosis and astrogliosis were also determined by IF
      microscopy. RESULTS: Pg/gingipain was detected in the hippocampi of mice in the
      experimental group by immunohistochemistry, confocal microscopy, and qPCR
      confirming the translocation of orally applied Pg to the brain. Pg/gingipain was
      localized intra-nuclearly and peri-nuclearly in microglia (Iba1+), astrocytes
      (GFAP+), neurons (NeuN+) and was evident extracellularly. Significantly greater
      levels of expression of IL6, TNFalpha and IL1beta were evident in experimental as
      compared to control group (p<0.01, p<0.00001, p<0.00001 respectively). In
      addition, microgliosis and astrogliosis were evident in the experimental but not
      in control group (p <0.01, p<0.0001 respectively). Neurodegeneration was evident
      in the experimental group based on a fewer number of intact neuronal cells
      assessed by NeuN positivity and rbFOX3 gene expression, and there was a greater
      number of degenerating neurons in the hippocampi of experimental mice assessed by
      Fluoro Jade C positivity. APP and BACE1 gene expression were increased in
      experimental group compared with control group (p<0.05, p<0.001 respectively).
      PSEN1 gene expression was higher in experimental than control group but the
      difference was not statistically significant (p = 0.07). ADAM10 gene expression
      was significantly decreased in experimental group compared with control group
      (p<0.01). Extracellular Abeta42 was detected in the parenchyma in the
      experimental but not in the control group (p< 0.00001). Finally, phospho-Tau
      (Ser396) protein was detected and NFTs were evident in experimental but not in
      the control group (p<0.00001). CONCLUSIONS: This study is the first to show
      neurodegeneration and the formation of extracellular Abeta42 in young adult WT
      mice after repeated oral application of Pg. The neuropathological features
      observed in this study strongly suggest that low grade chronic periodontal
      pathogen infection can result in the development of neuropathology that is
      consistent with that of AD.

PMID- 30281648
TI  - RAIDD mutations underlie the pathogenesis of thin lissencephaly (TLIS).
AB  - Abnormal regulation of caspase-2-mediated neuronal cell death causes
      neurodegenerative diseases and defective brain development. PIDDosome is caspase
      2 activating complex composed of PIDD, RAIDD, and caspase-2. Recent whole-exome
      sequencing study showed that the RAIDD mutations in the death domain (DD),
      including G128R, F164C, R170C, and R170H mutations, cause thin lissencephaly
      (TLIS) by reducing caspase-2-mediated neuronal apoptosis. Given that the
      molecular structure of the RAIDD DD:PIDD DD complex is available, in this study,
      we analyzed the molecular mechanisms underlying TLIS caused by the RAIDD TLIS
      variants by performing mutagenesis and biochemical assays.

PMID- 30281650
TI  - Telomere shortening in breast cancer cells (MCF7) under treatment with low doses
      of the benzylisoquinoline alkaloid chelidonine.
AB  - Telomeres, the specialized dynamic structures at chromosome ends, regularly
      shrink with every replication. Thus, they function as an internal molecular clock
      counting down the number of cell divisions. However, most cancer cells escape
      this limitation by activating telomerase, which can maintain telomere length.
      Previous studies showed that the benzylisoquinoline alkaloid chelidonine
      stimulates multiple modes of cell death and strongly down-regulates telomerase.
      It is still unknown if down-regulation of telomerase by chelidonine boosts
      substantial telomere shortening. The breast cancer cell line MCF7 was
      sequentially treated with very low concentrations of chelidonine over several
      cell passages. Telomere length and telomerase activity were measured by a
      monochrome multiplex quantitative PCR and a q-TRAP assay, respectively. Changes
      in population size and doubling time correlated well with telomerase inhibition
      and telomere shortening. MCF7 cell growth was arrested completely after three
      sequential treatments with 0.1 MUM chelidonine, each ending after 48 h, while
      telomere length was reduced to almost 10% of the untreated control. However,
      treatment with 0.01 MUM chelidonine did not have any apparent consequence. In
      addition to dose and time dependent telomerase inhibition, chelidonine changed
      the splicing pattern of hTERT towards non-enzyme coding isoforms of the
      transcript. In conclusion, telomere length and telomere stability are strongly
      affected by chelidonine in addition to microtubule formation.

PMID- 30281651
TI  - The influence of hypoxia and prolonged exercise on attentional performance at
      high and extreme altitudes: A pilot study.
AB  - INTRODUCTION: Exposure to hypoxic conditions is reported to impair cognitive
      performance. Further, moderate physical exercise improves cognitive function, but
      little is known about the influence of exercise on cognitive function in hypoxia.
      Therefore, the current study aimed to examine the influence of hypoxia (HYP) and
      prolonged exercise (EX) on attentional performance. METHODS: A total of 80
      participants (female: n = 29; male: n = 51) were assigned to four groups: HYP +
      EX (n = 15), HYP (n = 25), EX (n = 21) and normoxia (NOR) (n = 21). The Frankfurt
      Attention Inventory-2 (FAIR-2) was performed at four testing points (day 1, 14,
      16 and 18) to assess attentional performance. All groups completed a pretest (D1)
      and a follow-up test (D18). In HYP + EX conditions, the cognitive task was
      performed in a hypoxic state after prolonged exercise (D14: 3950 m, D16: 5739 m)
      during a mountain climb on Mt. Kilimanjaro. Participants in HYP were tested under
      intermittent hypoxia at rest in a hypoxic chamber (D14: 3500 m, D16: 5800 m), and
      those in EX were tested under normoxia after prolonged exercise during a 7-day
      backcountry ski hiking tour. NOR was a control group, and participants completed
      all tests under normoxia and at rest. RESULTS: Hypoxia impaired the attentional
      functions performance value (PV) and continuity value (CV) for the HYP + EX (p =
      0.000) and HYP (L: p = 0.025; K: p = 0.043) groups at 5739 m and 5800 m,
      respectively, but not the function quality value (QV). In contrast, the EX group
      did not exhibit changes in attentional function. CONCLUSION: The current results
      suggest that attentional performance is impaired during extreme normobaric and
      hypobaric hypoxic exposure. We further conclude that greater cognitive impairment
      under hypobaric hypoxia during a mountain climb compared with normobaric hypoxia
      at rest is not caused by prolonged exercise, but may be influenced by other
      factors (e.g. low temperatures, dehydration, or sleep deprivation) that remain to
      be verified.

PMID- 30281652
TI  - Stride-to-stride fluctuations in transtibial amputees are not affected by changes
      in push-off mechanics from using different prostheses.
AB  - Stride-to-stride fluctuations of joint kinematics during walking reflect a highly
      structured organization that is characteristic of healthy gait. The organization
      of stride-to-stride fluctuations is disturbed in lower-limb prosthesis users, yet
      the factors contributing to this difference are unclear. One potential
      contributor to the changes in stride-to-stride fluctuations is the altered push
      off mechanics experienced by passive prosthesis users. The purpose of our study
      was to determine if changes in push-off mechanics affect stride-to-stride
      fluctuations in transtibial amputees. Twenty-two unilateral transtibial amputees
      were enrolled in the 6-week cross-over study, where High and Low Activity (based
      on the Medicare Functional Classification System) prostheses were worn for three
      weeks each. Data collection took place at the end of the third week. Participants
      walked on a treadmill in a motion capture laboratory to quantify stride-to-stride
      fluctuations of the lower extremity joint angle trajectories using the largest
      Lyapunov Exponent, and over floor-embedded force platforms to enable calculating
      push-off work from the prosthesis and the sound limb. Push-off work was 140%
      greater in the High Activity prosthesis compared to the Low Activity prosthesis
      (p < 0.001), however no significant change was observed in stride-to-stride
      fluctuations of the ankle between the two prosthesis types (p = 0.576). There was
      no significant correlation between changes in prosthesis push-off work and the
      largest Lyapunov exponent. Though differences in push-off work were observed
      between the two prosthesis types, stride-to-stride fluctuations remained similar,
      indicating that prosthesis propulsion mechanics may not be a strong determinant
      of stride-to-stride fluctuations in unpowered transtibial prosthesis users.

PMID- 30281653
TI  - Temporal clustering analysis of endothelial cell gene expression following
      exposure to a conventional radiotherapy dose fraction using Gaussian process
      clustering.
AB  - The vascular endothelium is considered as a key cell compartment for the response
      to ionizing radiation of normal tissues and tumors, and as a promising target to
      improve the differential effect of radiotherapy in the future. Following
      radiation exposure, the global endothelial cell response covers a wide range of
      gene, miRNA, protein and metabolite expression modifications. Changes occur at
      the transcriptional, translational and post-translational levels and impact cell
      phenotype as well as the microenvironment by the production and secretion of
      soluble factors such as reactive oxygen species, chemokines, cytokines and growth
      factors. These radiation-induced dynamic modifications of molecular networks may
      control the endothelial cell phenotype and govern recruitment of immune cells,
      stressing the importance of clearly understanding the mechanisms which underlie
      these temporal processes. A wide variety of time series data is commonly used in
      bioinformatics studies, including gene expression, protein concentrations and
      metabolomics data. The use of clustering of these data is still an unclear
      problem. Here, we introduce kernels between Gaussian processes modeling time
      series, and subsequently introduce a spectral clustering algorithm. We apply the
      methods to the study of human primary endothelial cells (HUVECs) exposed to a
      radiotherapy dose fraction (2 Gy). Time windows of differential expressions of
      301 genes involved in key cellular processes such as angiogenesis, inflammation,
      apoptosis, immune response and protein kinase were determined from 12 hours to 3
      weeks post-irradiation. Then, 43 temporal clusters corresponding to profiles of
      similar expressions, including 49 genes out of 301 initially measured, were
      generated according to the proposed method. Forty-seven transcription factors
      (TFs) responsible for the expression of clusters of genes were predicted from
      sequence regulatory elements using the MotifMap system. Their temporal profiles
      of occurrences were established and clustered. Dynamic network interactions and
      molecular pathways of TFs and differential genes were finally explored, revealing
      key node genes and putative important cellular processes involved in tissue
      infiltration by immune cells following exposure to a radiotherapy dose fraction.

PMID- 30281654
TI  - Utility of reticulocyte haemoglobin content and percentage hypochromic red cells
      as markers of iron deficiency anaemia among black CKD patients in South Africa.
AB  - INTRODUCTION: Iron deficiency anaemia (IDA) worsens the prognosis and outcomes of
      chronic kidney disease (CKD). However, while the haemoglobin level is unreliable
      for early detection of IDA, reticulocyte haemoglobin content (CHr) and
      hypochromic red cells (%HYPO) are early markers of IDA. METHODS: This was a cross
      sectional study of black adult participants (n = 258) with CKD and apparently
      healthy members of staff and patients' relatives (n = 141) at the Charlotte
      Maxeke Johannesburg Academic Hospital, South Africa, between 1 June 2016 and 31
      December 2016. Serum iron, serum ferritin and transferrin were measured using
      standard laboratory methods, while the haematology analyser was employed to
      measure CHr and %HYPO. The validity of CHr and %HYPO as markers of IDA were
      evaluated. Multivariable binary logistic regression was conducted to determine
      predictors of the relationship between IDA, CHr and %HYPO. The area under the
      receiver operator characteristics (ROC) curve (AUC) of the final models were
      utilised to evaluate the discriminatory value of CHr and %HYPO respectively.
      RESULTS: About one-quarter (26.1%) of the participants had IDA which was more
      than three times more frequent among CKD patients, compared to controls (35.3% vs
      9.2%); 32.3% (95%CI: 27.90%- 37.10%) of the study population had iron deficiency
      without anaemia and the prevalence of iron deficiency without anaemia was lower
      in CKD patients compared to controls (29.5% vs 37.6%). The mean age of CKD
      patients was higher than in controls (52.7 +/-14.3 vs 40.4 +/-12.6 years, P
      value<0.001). The sensitivity and specificity for diagnosing IDA among CKD
      participants was 62.6% and 80.2% respectively for CHr (at a cut-off value of
      <28pg) and 63.3% and 79.8% respectively for %HYPO. CKD participants with CHr
      levels >28pg were 82% less likely to be diagnosed as having IDA as compared to
      those with CHr levels <= 28pg) (adj odds ratio = 0.18, 95% CI: 0.09-0.37). The
      AUC of CHr (0.81, 95% CI: 0.76-0.87) was higher than the AUC of %HYPO (0.76,
      95%CI: 0.70-0.82). CONCLUSION: The diagnostic usefulness of CHr and the screening
      performance of %HYPO in predicting IDA among CKD patients are high. Their lower
      cost compared to conventional markers of ID recommend their use in clinical
      practice. Further cost effectiveness studies of these parameters are warranted.

PMID- 30281655
TI  - TIMP3 and TIMP1 are risk genes for bicuspid aortic valve and aortopathy in Turner
      syndrome.
AB  - Turner syndrome is caused by complete or partial loss of the second sex
      chromosome, occurring in ~1 in 2,000 female births. There is a greatly increased
      incidence of aortopathy of unknown etiology, including bicuspid aortic valve
      (BAV), thoracic aortic aneurysms, aortic dissection and rupture. We performed
      whole exome sequencing on 188 Turner syndrome participants from the National
      Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular
      Related Conditions (GenTAC). A gene-based burden test, the optimal sequence
      kernel association test (SKAT-O), was used to evaluate the data with BAV and
      aortic dimension z-scores as covariates. Genes on chromosome Xp were analyzed for
      the potential to contribute to aortopathy when hemizygous. Exome analysis
      revealed that TIMP3 was associated with indices of aortopathy at exome-wide
      significance (p = 2.27 x 10-7), which was replicated in a separate cohort. The
      analysis of Xp genes revealed that TIMP1, which is a functionally redundant
      paralogue of TIMP3, was hemizygous in >50% of our discovery cohort and that
      having only one copy of TIMP1 increased the odds of having aortopathy (OR = 9.76,
      95% CI = 1.91-178.80, p = 0.029). The combinatorial effect of a single copy of
      TIMP1 and TIMP3 risk alleles further increased the risk for aortopathy (OR =
      12.86, 95% CI = 2.57-99.39, p = 0.004). The products of genes encoding tissue
      inhibitors of matrix metalloproteinases (TIMPs) are involved in development of
      the aortic valve and protect tissue integrity of the aorta. We propose that the
      combination of X chromosome TIMP1 hemizygosity and variants of its autosomal
      paralogue TIMP3, significantly increases the risk of aortopathy in Turner
      syndrome.

PMID- 30281656
TI  - Population genetic analysis of autophagy and phagocytosis genes in Drosophila
      melanogaster and D. simulans.
AB  - Autophagy and phagocytosis are cellular immune mechanisms for internalization and
      elimination of intracellular and extracellular pathogens. Some pathogens have
      evolved the ability to inhibit or manipulate these processes, raising the
      prospect of adaptive reciprocal co-evolution by the host. We performed population
      genetic analyses on phagocytosis and autophagy genes in Drosophila melanogaster
      and D. simulans to test for molecular evolutionary signatures of immune
      adaptation. We found that phagocytosis and autophagy genes as a whole exhibited
      an elevated level of haplotype homozygosity in both species. In addition, we
      detected signatures of recent selection, notably in the Atg14 and Ykt6 genes in
      D. melanogaster and a pattern of elevated sequence divergence in the genderblind
      (gb) gene on the D. simulans lineage. These results suggest that the evolution of
      the host cellular immune system as a whole may be shaped by a dynamic conflict
      between Drosophila and its pathogens even without pervasive evidence of strong
      adaptive evolution at the individual gene level.

PMID- 30281657
TI  - Limited field radiation therapy results in decreased bone fracture toughness in a
      murine model.
AB  - Fragility fractures are a well-known complication following oncologic
      radiotherapy, and it is suspected that radiation-induced embrittlement of bone
      within the treatment field may contribute to fracture risk. To explore this
      phenomenon, a mouse model (BALB/cJ) of fractionated, limited field, bilateral
      hindlimb irradiation (4x5 Gy) was used. The effects of radiation on femoral
      (cortical) bone fracture toughness, morphology, and biochemistry-including
      advanced glycation end products (AGEs)-were quantified and compared to Sham group
      samples prior to irradiation and at 0, 4, 8, and 12 weeks post-irradiation.
      Additionally, alterations to bone fracture toughness mediated directly by
      radiation (independent of cellular mechanisms) were determined using devitalized
      mouse cadaver femurs. Finally, the contribution of AGEs to reduced fracture
      toughness was examined by artificially ribosylating mouse femurs ex vivo. These
      data demonstrate that in vivo irradiation results in an immediate (-42% at 0
      weeks, p < 0.001) and sustained (-28% at 12 weeks, p < 0.001) decrease in
      fracture toughness with small changes in morphology (-5% in cortical area at 12
      weeks), and minimal changes in bone composition (tissue mineral density,
      mineral:matrix ratio, and AGE content). Irradiation of devitalized femurs also
      reduced fracture toughness (-29%, p < 0.001), but to a lesser extent than was
      seen in vivo. While artificial ribosylation decreased fracture toughness with
      time, the extent of glycation needed to induce this effect exceeded the AGE
      accumulation that occurred in vivo. Overall, hindlimb irradiation induced a
      substantial and sustained decrease in bone fracture toughness. Approximately half
      of this decrease in fracture toughness is due to direct radiation damage,
      independent of cellular remodeling. Collagen glycation in vivo was not
      substantially altered, suggesting other matrix changes may contribute to post
      radiotherapy bone embrittlement.

PMID- 30281658
TI  - Long-term results of posterior cruciate ligament tear with or without
      reconstruction: A nationwide, population-based cohort study.
AB  - BACKGROUND: There is increasing interest in the long-term outcomes of patients
      with posterior cruciate ligament (PCL) tears following conservative treatment or
      reconstruction. However, limited information is available regarding these results
      because of the relative rarity of cases and lack of long-term follow-up. PURPOSE:
      The goals of this study are to (1) compare the occurrence of secondary meniscal
      tears, osteoarthritis (OA) or subsequent total knee replacement (TKR) in patients
      with or without PCL injury, and (2) evaluate the potential protective effect of
      PCL reconstruction against long-term sequela in patients with PCL deficiency.
      STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective
      cohort study evaluated the long-term results of PCL deficiency with or without
      reconstruction in Taiwan based on data from the National Health Insurance
      Research Database (NHIRD) from 2000 to 2015. The cumulative incidence rates of
      meniscus tear, OA and TKR were analyzed using the Kaplan-Meier estimator. Cox
      proportional hazards models were applied to estimate hazard ratios (HRs) and 95%
      confidence intervals (CIs). RESULTS: A total of 4,169 patients diagnosed with PCL
      tear from 2000 to 2015 in Taiwan were included in the study. There was a higher
      cumulative incidence of meniscus tear (1.13%), OA (2.71%) and subsequent TKR
      (0.91%) among patients with a PCL tear than among patients without one (0.22%,
      1.90%, 0.62%; all p < 0.05). PCL reconstruction patients had a decreased
      cumulative incidence of meniscus tear (0.41%), OA (2.30%) and subsequent TKR
      (0.48%) compared with non-reconstructed patients (2.44%, 3.46%, 1.69%; all p <
      0.05). After adjusting for covariates, PCL-injured patients who underwent
      reconstruction within one year after PCL injury showed a significantly lower risk
      of subsequent sequelae than those who never underwent reconstruction (within 1
      month: adjusted HR = 0.390, 95% CI = 0.284-0.535; 1 month to 1 year: adjusted HR
      = 0.546, 95% CI = 0.398-0.748). CONCLUSIONS: Patients with PCL tears have a
      significantly higher risk of meniscus tear, OA and subsequent TKR than patients
      without PCL tears. PCL reconstruction could decrease the cumulative incidence of
      these outcomes. The results suggest that PCL-injured patients should undergo
      reconstruction as early as possible (within one year) to reduce the risk of
      further degeneration.

PMID- 30281659
TI  - Trend in the nutritional status of children aged 2-7 years in Luoding city,
      China: A panel study from 2004 to 2013.
AB  - To examine trends in the prevalence of wasting, stunting, overweight, and obesity
      among children in Luoding, a lower-middle-income city in southern China, we
      collected height, weight and other information on 65,908 pre-school children aged
      2 to 7 years from 23 kindergartens, in which health examinations were conducted
      annually between 2004 and 2013. We used the growth standards of the World Health
      Organization (WHO) to calculate Z-scores for height and body mass index (BMI),
      and used the cut-offs recommended by WHO to define wasting, stunting, overweight,
      and obesity for each child. From 2004 to 2013, the prevalence of overweight
      increased from 3.70% to 7.27% and of obesity increased from 1.04% to 2.08%.
      Meanwhile, the prevalence of wasting decreased from 0.91% to 0.72% and of
      stunting decreased from 9.29% to 5.22%. These trends suggest there was still a
      double burden of nutritional status there. The nutritional interventions focusing
      on pre-school children should be comprehensively elaborated in lower-middle
      income areas such as Luoding.

PMID- 30281661
TI  - Novel knowledge-based system with relation detection and textual evidence for
      question answering research.
AB  - With the development of large-scale knowledge bases (KBs), knowledge-based
      question answering (KBQA) has become an important research topic in recent years.
      The key task in KBQA is relation detection, which is the process of finding a
      compatible answer type for a natural language question and generating its
      corresponding structured query over a KB. However, existing systems often rely on
      shallow probabilistic methods, which are less expressive than deep semantic
      representation methods. In addition, since KBs are still far from complete, it is
      necessary to develop a new strategy that leverages unstructured resources outside
      of KBs. In this work, we propose a novel Question Answering method with Relation
      Detection and Textual Evidence (QARDTE). First, to address the semantic gap
      problem in relation detection, we use bidirectional long-short term memory
      networks with different levels of abstraction to better capture sentence
      structures. Our model achieves improved results with robustness against a wide
      diversity of expressions and questions with multiple relations. Moreover, to help
      compensate for the incompleteness of KBs, we utilize external unstructured text
      to extract additional supporting evidence and combine this evidence with relation
      information during the answer re-ranking process. In experiments on two well
      known benchmarks, our system achieves F1 values of 0.558 (+2.8%) and 0.663
      (+5.7%), which are state-of-the-art results that show significant improvement
      over existing KBQA systems.

PMID- 30281660
TI  - Magnitude and risk factors for hypertension among public servants in Tigray,
      Ethiopia: A cross-sectional study.
AB  - BACKGROUND: Hypertension is a globally recognized threat to social and economic
      development with premature morbidity and mortality. In middle and low-income
      countries hypertension appears to be increasing. However, sufficient data on this
      silent-killer is not available in Ethiopia. Therefore, this study examined the
      magnitude and risk factors for hypertension among public servants in Tigray,
      Ethiopia. METHODS: We used a cross-sectional survey from May-June 2016 among 1525
      public servants in Tigray region. Field workers collected data using a pre
      tested, standardized questionnaire. A multivariate logistic regression analysis
      conducted to identify risk factors for hypertension. Statistical significance was
      declared using a p-value<0.05 and 95% of confidence interval (CI) for an adjusted
      odds ratio (AOR). RESULTS: The overall prevalence of hypertension was 16% (95%
      CI: 13.10-21.9) and the proportion of awareness (96.7%), treatment (31.3%) and
      control of hypertension (40.1%) among employees. Being male [AOR = 2.06,
      95%CI:1.49, 2.84], ages groups of 30-49 years [AOR = 2.21, 95%CI:1.25, 3.89] and
      >50years [AOR = 3.61, 95% CI:1.93, 6.69], Body Mass Index(BMI); underweight [AOR
      = 0.40, 95% CI; 0.20, 0.78], overweight [AOR = 1.70, 95%CI; 1.22, 2.33] and
      obesity [AOR = 3.20, 95% CI; 1.78, 5.78] were determinants for hypertension.
      CONCLUSION: The prevalence of hypertension is relatively high in Mekelle city
      compared with previous reports. This study revealed that male sex, age-group, and
      BMI were evidenced as risk factors for hypertension. Policy makers need to
      consider sector wise integrating prevention and control of hypertension. Skilled
      based information, education and communication strategies should be designed and
      implemented to avoid unhealthy lifestyles, investing in workforces to eliminate
      the modifiable risk factors for non-communicable diseases and promote healthy
      practices.

PMID- 30281662
TI  - Broad range flavonoid profiling by LC/MS of soybean genotypes contrasting for
      resistance to Anticarsia gemmatalis (Lepidoptera: Noctuidae).
AB  - Attack by herbivores is a major biotic stress limiting the soybean crop
      production. Plant defenses against caterpillars include the production of
      secondary metabolites such as flavonoids, which constitute a diverse group of
      plant secondary metabolites. Thus, a more discriminate metabolic profiling
      between genotypes are important for a more comprehensive and reliable
      characterization of soybean resistance. Therefore, in this study a non-targeted
      LC/MS-based for analysis of flavonoid profiles of soybean genotypes contrasting
      to the resistance to A. gemmatalis was applied. Clustering analysis revealed
      profiles highly distinct between the susceptible UFV 105 AP and the resistant IAC
      17 genotypes. This comparative approach enables to identify directly from leaf
      extract some new compounds related to resistance, some of which were present in
      higher abundance specifically in the IAC 17 genotype: four Quercetin conjugates,
      Rutin (Quercetin 3-O-Rutinoside), Quercetin-3,7-O- di-glucoside, Quercetin-3-O
      rhamnosylglycoside-7-O-glucoside and Quercetin-3-O-rhamnopyranosyl
      glucopyranoside-rhamnopyranoside; two Genistein conjugates, Genistein-7-O
      diglucoside-dimalonylated and Genistein-7-O-6-O-malonylglucoside; and one
      Daidzein conjugate, Daidzein-7-O-Glucoside-malonate. The most abundant flavonoid
      glycoconjugates in soybean leaves belongs to Quercetin and Kaempferol classes.
      However, only one from the identified compounds was classified as a Kaempferol.
      The Kaempferol-3-O-L-rhamnopyranosyl-glucopyranoside showed high abundance in the
      resistant genotype IAC 17. The metabolic profiles generated by LC/MS allowed the
      reconstruction of the flavonoid biosynthetic pathways, which revealed a
      constitutive character for herbivory resistance in the resistant genotype IAC-17
      and a metabolic regulation for the rechanneling of Quercetin, Kaempferol and
      Genistein conjugates in soybean. Highest relative abundances were detected for
      glyconjugates, such as Rutin, Quercetin 3-O-rhamnosylglycoside-7-O-glucoside and
      Quercitin-3-O-rhamnopyranosyl-glucopyranoside-rhamnopyranoside in the leaves of
      the resistant genotype.

PMID- 30281663
TI  - Familial risks of ovarian cancer by age at diagnosis, proband type and histology.
AB  - Ovarian cancer is a heterogeneous disease. Data regarding familial risks for
      specific proband, age at diagnosis and histology are limited. Such data can
      assist genetic counseling and help elucidate etiologic differences among various
      histologic types of ovarian malignancies. By using the Swedish Family-Cancer
      Database, we calculated relative risks (RRs) for detailed family histories using
      a two-way comparison, which implied e.g. estimation of RRs for overall ovarian
      cancer when family history was histology-specific ovarian cancer, and conversely,
      RRs for histology-specific ovarian cancer when family history was overall ovarian
      cancer. In families of only mother, only sisters or both mother and sisters
      diagnosed with ovarian cancer, cancer risks for ovary were 2.40, 2.59 and 10.40,
      respectively; and were higher for cases diagnosed before the age of 50 years. All
      histological types showed a familial risk in two-way analyses, except mucinous
      and sex cord-stromal tumors. RRs for concordant histology were found for serous
      (2.47), endometrioid (3.59) and mucinous ovarian cancers (6.91). Concordant
      familial risks were highest for mucinous cancer; for others, some discordant
      associations, such as endometrioid-undifferentiated (9.27) and serous
      undifferentiated (4.80), showed the highest RRs. Familial risks are high for
      early-onset patients and for those with multiple affected relatives. Sharing of
      different histological types of ovarian cancer is likely an indication of the
      complexity of the underlying mechanisms.

PMID- 30281665
TI  - Genetic variation in a colonization specialist, Simulium ruficorne (Diptera:
      Simuliidae), the world's most widely distributed black fly.
AB  - The ability of aquatic insects to colonize Earth's most remote freshwater
      habitats, such as those of islands and deserts, is limited to select taxa. Among
      black flies, the premiere colonization specialist is Simulium ruficorne Macquart,
      the only species known from both the Afrotropical and Palearctic regions. We
      investigated the cytogenetics of S. ruficorne to gain insight into its wide
      geographic distribution and ability to colonize oceanic islands and deserts. On
      the basis of larval polytene chromosomes from 14 locations, we documented 17
      novel and previously known chromosomal rearrangements and established five
      cytoforms (A1, A2, B, C, and D), of which probably four (A1/A2, B, C, and D) are
      distinct species and two (A1 and A2) represent sex-chromosome polymorphism
      involving a heteroband in the long arm of chromosome III. The chromosome
      restructuring phenomena associated with the five cytoforms are consistent with
      the trend in the Simuliidae that one and the same rearrangement can assume
      different functions in the various descendants of a common ancestor in which the
      rearrangement was polymorphic. The most widely distributed cytoforms are A1 and
      A2, which are found in North Africa, the Canary Islands, and Majorca. Simulium
      ruficorne, the only known black fly in the Hoggar Mountains of the central Sahara
      Desert, represents a cohesive population of cytoform A1 little differentiated
      from other North African populations of A1 and A2. Cytoform B inhabits the West
      African mainland, cytoform C is on Tenerife, and cytoform D is on Cape Verde. We
      suggest that dispersal and colonization specialists, such as S. ruficorne, are
      multivoltine inhabitants of temporary streams, and must relocate as their
      habitats deteriorate. Simulium ruficorne, therefore, should have adaptations that
      contribute to successful dispersal and colonization, perhaps largely
      physiological in nature, such as tolerance of high temperatures and droughts.

PMID- 30281664
TI  - Structural characterization of four different naturally occurring porcine
      collagen membranes suitable for medical applications.
AB  - Collagen is the main structural element of connective tissues, and its favorable
      properties make it an ideal biomaterial for regenerative medicine. In dental
      medicine, collagen barrier membranes fabricated from naturally occurring tissues
      are used for guided bone regeneration. Since the morphological characteristics of
      collagen membranes play a crucial role in their mechanical properties and affect
      the cellular behavior at the defect site, in-depth knowledge of the structure is
      key. As a base for the development of novel collagen membranes, an extensive
      morphological analysis of four porcine membranes, including centrum tendineum,
      pericardium, plica venae cavae and small intestinal submucosa, was performed.
      Native membranes were analyzed in terms of their thickness. Second harmonic
      generation and two-photon excitation microscopy of the native membranes showed
      the 3D architecture of the collagen and elastic fibers, as well as a volumetric
      index of these two membrane components. The surface morphology, fiber
      arrangement, collagen fibril diameter and D-periodicity of decellularized
      membranes were investigated by scanning electron microscopy. All the membrane
      types showed significant differences in thickness. In general, undulating
      collagen fibers were arranged in stacked layers, which were parallel to the
      membrane surface. Multiphoton microscopy revealed a conspicuous superficial
      elastic fiber network, while the elastin content in deeper layers varied. The
      elastin/collagen volumetric index was very similar in the investigated membranes
      and indicated that the collagen content was clearly higher than the elastin
      content. The surface of both the pericardium and plica venae cavae and the
      cranial surface of the centrum tendineum revealed a smooth, tightly arranged and
      crumpled morphology. On the caudal face of the centrum tendineum, a compact
      collagen arrangement was interrupted by clusters of circular discontinuities. In
      contrast, both surfaces of the small intestinal submucosa were fibrous, fuzzy and
      irregular. All the membranes consisted of largely uniform fibrils displaying the
      characteristic D-banding. This study reveals similarities and relevant
      differences among the investigated porcine membranes, suggesting that each
      membrane represents a unique biomaterial suitable for specific applications.

PMID- 30281667
TI  - Weather field reconstruction using aircraft surveillance data and a novel meteo
      particle model.
AB  - Wind and temperature data are important parameters in aircraft performance
      studies. The lack of accurate measurements of these parameters forces researchers
      to rely on numerical weather prediction models, which are often filtered for a
      larger area with decreased local accuracy. Aircraft, however, also transmit
      information related to weather conditions, in response to interrogation by air
      traffic controller surveillance radars. Although not intended for this purpose,
      aircraft surveillance data contains information that can be used for weather
      models. This paper presents a method that can be used to reconstruct a weather
      field from surveillance data that can be received with a simple 1090 MHz
      receiver. Throughout the paper, we answer two main research questions: how to
      accurately infer wind and temperature from aircraft surveillance data, and how to
      reconstruct a real-time weather grid efficiently. We consider aircraft as moving
      sensors that measure wind and temperature conditions indirectly at different
      locations and flight levels. To address the first question, aircraft barometric
      altitude, ground velocity, and airspeed are decoded from down-linked surveillance
      data. Then, temperature and wind observations are computed based on aeronautical
      speed conversion equations. To address the second question, we propose a novel
      Meteo-Particle (MP) model for constructing the wind and temperature fields. Short
      term local prediction is also possible by employing a predictor layer. Using an
      unseen observation test dataset, we are able to validate that the mean absolute
      errors of inferred wind and temperature using MP model are 67% and 26% less than
      using the interpolated model based on GFS reanalysis data.

PMID- 30281666
TI  - The assessment of successful emotion regulation skills use: Development and
      validation of an English version of the Emotion Regulation Skills Questionnaire.
AB  - Emotion regulation has become an important topic in mental health and
      psychotherapy research. Skills supposingly relevant for adaptive responses
      towards emotions include the abilities to be consciously aware of emotions,
      identify and correctly label emotions, understand what has caused and maintains
      one's present emotions, modify the intensity or duration of one's emotions,
      accept and tolerate undesired emotions, confront situations likely to cue
      negative emotions, and provide effective self-support when working to cope with
      challenging emotions. To economically assess these abilities, a self-report
      measure has been developed in German and validated in various studies. To
      facilitate the use of the measure in English speaking countries, we have
      developed and validated an English version of the Emotion Regulation Skills
      Questionnaire (ERSQ) in a student sample (n = 263) and a sample of individual
      clinical sample (n = 35). Findings from this study provide significant evidence
      for the reliability and validity of the ERSQ. Thus, the measure can be used to
      assess a broad range of important emotion regulation skills in an economic way.

PMID- 30281668
TI  - Country-specific costs of implementing the WHO FCTC tobacco control policies and
      potential financing sources.
AB  - BACKGROUND: One of the major obstacles to the full implementation of the World
      Health Organization (WHO) Framework Convention of Tobacco Control (FCTC) tobacco
      control measures is the lack of sustainable financing resources. GOAL: To update
      and simulate country-specific indicators that are highly relevant to the costs
      and financial resources of the treaty policy implementation. We also developed an
      Excel tool for simulation and assessed the aggregated-level indicators by the
      2016 World Bank income groups. APPROACHES: Using mostly 2016 data or 2014-15 data
      if 2016 one are not available, we updated five indicators relevant to the treaty
      implementation, which are the gap between current and desirable policy
      implementation, cigarette affordability, the costs of implementing best- buy
      tobacco control policies, the number of smoking-attributable deaths, and the
      simulated tax revenue resulting from a $1 tax increase. We also aggregated
      indicators and simulation results by the World Bank income groups, encompassing
      the five indicators and the reduction in smoking and in attributable deaths due
      to a hypothetical 1I$ tax increase. Finally, the policy implementation cost was
      compared with tax revenue and revenue increases. FINDINGS: As of 2016, smoking
      remains one of the leading causes of premature deaths worldwide while the
      implementation of best-buy tobacco control policies was below the recommended
      levels. Meanwhile, there was room to further increase cigarette taxes and prices,
      as cigarettes remained affordable in many countries. The total costs of
      implementing best-buy policies in the next 15 years merely account for 8.3% of
      the 2016 excise tax revenue, indicating that a small proportion of annual tax
      revenue could fund the implementation of tobacco control policies recommended by
      the WHO FCTC. CONCLUSIONS: Increasing taxes could have a multiplier impact on
      curbing tobacco use through aiding the implementation of the WHO FCTC.

PMID- 30281669
TI  - Integrin-targeted quantitative optoacoustic imaging with MRI correlation for
      monitoring a BRAF/MEK inhibitor combination therapy in a murine model of human
      melanoma.
AB  - PURPOSE: To investigate alphavbeta3-integrin-targeted optoacoustic imaging and
      MRI for monitoring a BRAF/MEK inhibitor combination therapy in a murine model of
      human melanoma. MATERIALS AND METHODS: Human BRAF V600E-positive melanoma
      xenograft (A375)-bearing Balb/c nude mice (n = 10) were imaged before (day 0) and
      after (day 7) a BRAF/MEK inhibitor combination therapy (encorafenib, 1.3 mg/kg/d;
      binimetinib, 0.6 mg/kg/d, n = 5) or placebo (n = 5), respectively. Optoacoustic
      imaging was performed on a preclinical system unenhanced and 5 h after i. v.
      injection of an alphavbeta3-integrin-targeted fluorescent probe. The alphavbeta3
      integrin-specific tumor signal was derived by spectral unmixing. For morphology
      based tumor response assessments, T2w MRI data sets were acquired on a clinical 3
      Tesla scanner. The imaging results were validated by multiparametric
      immunohistochemistry (beta3 -integrin expression, CD31 -microvascular density, Ki
      67 -proliferation). RESULTS: The alphavbeta3-integrin-specific tumor signal was
      significantly reduced under therapy, showing a unidirectional decline in all
      animals (from 7.98+/-2.22 to 1.67+/-1.30; p = 0.043). No significant signal
      change was observed in the control group (from 6.60+/-6.51 to 3.67+/-1.93; p =
      0.500). Immunohistochemistry revealed a significantly lower integrin expression
      (beta3: 0.20+/-0.02 vs. 0.39+/-0.05; p = 0.008) and microvascular density (CD31:
      119+/-15 vs. 292+/-49; p = 0.008) in the therapy group. Tumor volumes increased
      with no significant intergroup difference (therapy: +107+/-42 mm3; control +112+/
      44mm3, p = 0.841). In vivo blocking studies with alphavbeta3-integrin antagonist
      cilengitide confirmed the target specificity of the fluorescent probe.
      CONCLUSIONS: alphavbeta3-integrin-targeted optoacoustic imaging allowed for the
      early non-invasive monitoring of a BRAF/MEK inhibitor combination therapy in a
      murine model of human melanoma, adding molecular information on tumor receptor
      status to morphology-based tumor response criteria.

PMID- 30281670
TI  - The eNOS-NO pathway attenuates kidney dysfunction via suppression of inflammasome
      activation in aldosterone-induced renal injury model mice.
AB  - Hypertension causes vascular complications, such as stroke, cardiovascular
      disease, and chronic kidney disease (CKD). The relationship between endothelial
      dysfunction and progression of kidney disease is well known. However, the
      relationship between the eNOS-NO pathway and chronic inflammation, which is a
      common pathway for the progression of kidney disease, remains unexplored. We
      performed in vivo experiments to determine the role of the eNOS-NO pathway by
      using eNOS-deficient mice in a hypertensive kidney disease model. All mice were
      unilateral nephrectomized (Nx). One week after Nx, the mice were randomly divided
      into two groups: the aldosterone infusion groups and the vehicle groups. All mice
      also received a 1% NaCl solution instead of drinking water. The aldosterone
      infusion groups were treated with hydralazine to correct blood pressure
      differences. After four weeks of drug administration, all mice were euthanized,
      and blood and kidney tissue samples were collected. In the results, NLRP3
      inflammasome activation was elevated in the kidneys of the eNOS-deficient mice,
      and tubulointerstitial fibrosis was accelerated. Suppression of inflammasome
      activation by knocking out ASC prevented tubulointerstitial injury in the eNOS
      knockout mice, indicating that the eNOS-NO pathway is involved in the development
      of kidney dysfunction through acceleration of NLRP3 inflammasome in macrophages.
      We revealed that endothelial function, particularly the eNOS-NO pathway,
      attenuates the progression of renal tubulointerstitial injury via suppression of
      inflammasome activation. Clinically, patients who develop vascular endothelial
      dysfunction have lifestyle diseases, such as hypertension or diabetes, and are
      known to be at risk for CKD. Our study suggests that the eNOS-NO pathway could be
      a therapeutic target for the treatment of chronic kidney disease associated with
      endothelial dysfunction.

PMID- 30281671
TI  - Scientific evidence underlying the American College of Gastroenterology's
      clinical practice guidelines.
AB  - BACKGROUND: Clinical practice guidelines contain recommendations for physicians
      to determine the most appropriate care for patients. These guidelines
      systematically combine scientific evidence and clinical judgment, culminating in
      recommendations intended to optimize patient care. The recommendations in CPGs
      are supported by evidence which varies in quality. We aim to survey the clinical
      practice guidelines created by the American College of Gastroenterology, report
      the level of evidence supporting their recommendations, and identify areas where
      evidence can be improved with additional research. METHODS: We extracted 1328
      recommendations from 39 clinical practice guidelines published by the American
      College of Gastroenterology. Several of the clinical practice guidelines used the
      differing classifications of evidence for their recommendations. To standardize
      our results, we devised a uniform system for evidence. RESULTS: A total of 39
      clinical practice guidelines were surveyed in our study. Together they account
      for 1328 recommendations. 693 (52.2%) of the recommendations were based on low
      evidence, indicating poor evidence or expert opinion. Among individual
      guidelines, 13/39 (33.3%) had no recommendations based on high evidence.
      CONCLUSION: Very few recommendations made by the American College of
      Gastroenterology are supported by high levels of evidence. More than half of all
      recommendations made by the American College of Gastroenterology are based on low
      quality evidence or expert opinion.

PMID- 30281672
TI  - Positive perception of aging is a key predictor of quality-of-life in aging
      people.
AB  - OBJECTIVE: We conducted a cross-sectional survey in France in a cohort over 55
      years of age to characterize the impact of psychological dimensions on quality-of
      life (QoL). METHODS: The predictors of QoL in relation with aging were studied
      using an adapted quality-of-life model, based on emotional, cognitive and
      physical symptoms, functional status, and general health perception. Adding
      psychological dimensions such as self-esteem, psychological distress, perceptions
      of ageing and coping, was hypothesized to improve the QoL model. Responses were
      analyzed using structural equation modeling and path analysis. RESULTS: The study
      involved 258 participants, mean age 66.9+/-7.9 years. Psychological distress and
      positive perception of aging exhibited the strongest direct impact on QoL
      (p<0.0001). Psychological distress also appeared to be mediator on QoL for
      perceived health status, self-esteem and negative perception of aging. Coping
      centred on emotion exhibited direct impact on self-esteem and so, indirect impact
      on QoL (p = 0.0002). Perception of personal financial situation (p = 0.0007) and
      coping centred on social support (p = 0.02) appeared as direct mediators
      influencing QoL. CONCLUSIONS: Psychological dimensions are predictors of QOL and
      have to be taken into account to maximize the resources with a view to successful
      aging. Further interventions targeting successful aging should focus on positive
      perception aging.

PMID- 30281673
TI  - Structure and development of flowers and inflorescences in Peraceae and
      Euphorbiaceae and the evolution of pseudanthia in Malpighiales.
AB  - Pseudanthia are reduced and compact inflorescences which apparently had
      independent evolution in Euphorbiaceae and Peraceae within Malpighiales. In order
      to analyze the hypothesis that the different pseudanthia found in Malpighiales
      have non-homologous developmental steps, we studied the inflorescence and flower
      development in the three Malpighiales genera that present this type of
      inflorescence-Dalechampia (Acalyphoideae/Euphorbiaceae), Euphorbia
      (Euphorbioideae/Euphorbiaceae), and Pera (Peraceae)-and compared them to that of
      Joannesia (Crotonoideae/Euphorbiaceae), which does not present a pseudanthium.
      Inflorescences and flowers were analyzed using light microscopy and scanning
      electron microscopy. Dalechampia and Euphorbia have protogynic bisexual
      pseudanthia, with unisexual perianthed flowers in Dalechampia, and achlamydeous
      flowers in Euphorbia. Pera has unisexual pseudanthia and the male flowers have a
      vestigial calyx and the female flowers are achlamydeous. Joannesia flowers are
      very distinct when compared to the pseudanthia flowers, as they are composed of
      all the whorls and there is no reduction. In the early stages of development, the
      first structures to be formed in the pseudanthia are the different series of
      bracts, including outer, involucral and involucel bracts. The floral primordia
      are initiated almost simultaneously with the involucre. Although the different
      morphology, the early inflorescence followed the same branching pattern in all
      studied genera, and the number and elongation of the branches were affected by
      the early female flower development in the terminal position. We suggest that the
      different pseudanthia evolved via process of floral whorl reduction and
      reorganization of flowers in the inflorescence axes, especially the position of
      female and male flowers and elongation or shortening of the branches. The sex of
      the terminal flower is a developmental key, i.e., the protogynic development
      deeply affects the pseudanthia growth, reducing the ramification and elongation
      of the axes.

PMID- 30281675
TI  - Linking root exudates to functional plant traits.
AB  - Primary and secondary metabolites exuded by plant roots have mainly been studied
      under laboratory conditions, while knowledge of root exudate patterns of plants
      growing in natural communities is very limited. Focusing on ten common European
      grassland plant species, we asked to which degree exuded metabolite compositions
      are specific to species or growth forms (forbs and grasses), depend on
      environments and local neighbourhoods, and reflect traditional plant functional
      traits. Root exudates were collected under field conditions and analysed using a
      non-targeted gas chromatography coupled mass spectrometry (GC-MS) approach. In
      total, we annotated 153 compounds of which 36 were identified by structure and
      name as metabolites mainly derived from the primary metabolism. Here we show by
      using variance partitioning, that the composition of exuded polar metabolites was
      mostly explained by plot identity, followed by plant species identity while plant
      species composition of the local neighbourhood played no role. Total and root dry
      biomass explained the largest proportion of variance in exudate composition, with
      additional variance explained by traditional plant traits. Although the exudate
      composition was quite similar between the two growth forms, we found some
      metabolites that occurred only in one of the two growth forms. Our study
      demonstrated the feasibility of measuring polar exudates under non-sterile field
      conditions by mass spectrometry, which opens new avenues of research for
      functional plant ecology.

PMID- 30281674
TI  - Rare haplotype load as marker for lethal mutagenesis.
AB  - RNA viruses replicate with a template-copying fidelity, which lies close to an
      extinction threshold. Increases of mutation rate by nucleotide analogues can
      drive viruses towards extinction. This transition is the basis of an antiviral
      strategy termed lethal mutagenesis. We have introduced a new diversity index, the
      rare haplotype load (RHL), to describe NS5B (polymerase) mutant spectra of
      hepatitis C virus (HCV) populations passaged in absence or presence of the
      mutagenic agents favipiravir or ribavirin. The increase in RHL is more prominent
      in mutant spectra whose expansions were due to nucleotide analogues than to
      multiple passages in absence of mutagens. Statistical tests for paired
      mutagenized versus non-mutagenized samples with 14 diversity indices show that
      RHL provides consistently the highest standardized effect of mutagenic treatment
      difference for ribavirin and favipiravir. The results indicate that the
      enrichment of viral quasispecies in very low frequency minority genomes can serve
      as a robust marker for lethal mutagenesis. The diagnostic value of RHL from deep
      sequencing data is relevant to experimental studies on enhanced mutagenesis of
      viruses, and to pharmacological evaluations of inhibitors suspected to have a
      mutagenic activity.

PMID- 30281676
TI  - Rapid capture and detection of ostreid herpesvirus-1 from Pacific oyster
      Crassostrea gigas and seawater using magnetic beads.
AB  - Ostreid herpesvirus-1 (OsHV-1) has been involved in mass mortality episodes of
      Pacific oysters Crassostrea gigas throughout the world, causing important
      economic losses to the aquaculture industry. In the present study, magnetic beads
      (MBs) coated with an anionic polymer were used to capture viable OsHV-1 from two
      types of naturally infected matrix: oyster homogenate and seawater. Adsorption of
      the virus on the MBs and characterisation of the MB-virus conjugates was
      demonstrated by real-time quantitative PCR (qPCR). To study the infective
      capacity of the captured virus, MB-virus conjugates were injected in the adductor
      muscle of naive spat oysters, using oyster homogenate and seawater without MBs as
      positive controls, and bare MBs and sterile water as negative controls.
      Mortalities were induced after injection with MB-virus conjugates and in positive
      controls, whereas no mortalities were recorded in negative controls. Subsequent
      OsHV-1 DNA and RNA analysis of the oysters by qPCR and reverse transcription qPCR
      (RT-qPCR), respectively, confirmed that the virus was the responsible for the
      mortality event and the ability of the MBs to capture viable viral particles. The
      capture of viable OsHV-1 using MBs is a rapid and easy isolation method and a
      promising tool, combined with qPCR, to be applied to OsHV-1 detection in
      aquaculture facilities.

PMID- 30281677
TI  - Associations between poverty, mental health and substance use, gender power, and
      intimate partner violence amongst young (18-30) women and men in urban informal
      settlements in South Africa: A cross-sectional study and structural equation
      model.
AB  - : Research suggests that poverty is a key driver of intimate partner violence
      (IPV), however detailed analysis suggests that this relationship is not clear,
      either for women's experience or men's perpetration of IPV. We explored
      associations between poverty and IPV using cross-sectional data from the Stepping
      Stones and Creating Futures cluster randomized control trial, in urban informal
      settlements in Durban, South Africa, with young (18-30) people. Using logistic
      regression and structural equation modelling we assess associations between
      poverty and women's experience and men's perpetration of physical and/or sexual
      IPV in the past 12 months. 680 women and 677 men were recruited into the study
      between September 2015 and September 2016. The analyses highlight how specific
      forms or measures of poverty intersecting with gender identities shape IPV. For
      men we found indicators of economic provision were associated with IPV
      perpetration, while for women food-insecurity was key to IPV experience. We also
      found similarities between women and men. First, food-insecurity and childhood
      traumas shaped pathways to substance misuse and poor mental health that increased
      IPV. Second, there was a resilience pathway in both models, whereby those with
      more education had increased gender equitable attitudes and fewer controlling
      behaviours, which reduced IPV. Interventions to reduce IPV need to work to reduce
      household food insecurity, but these need to be combined with gender
      transformative interventions. Interventions should also focus on reducing the
      impact of mental health and substance misuse. Finally, working to increase
      educational attainment is a long-term critical intervention to reduce IPV. TRIAL
      REGISTRATION: NCT03022370. Registered 13 January 2017, retrospectively
      registered.

PMID- 30281678
TI  - Whole-exome sequencing capture kit biases yield false negative mutation calls in
      TCGA cohorts.
AB  - The Cancer Genome Atlas (TCGA) provides a genetic characterization of more than
      ten thousand tumors, enabling the discovery of novel driver mutations, molecular
      subtypes, and enticing drug targets across many histologies. Here we investigated
      why some mutations are common in particular cancer types but absent in others. As
      an example, we observed that the gene CCDC168 has no mutations in the stomach
      adenocarcinoma (STAD) cohort despite its common presence in other tumor types.
      Surprisingly, we found that the lack of called mutations was due to a systematic
      insufficiency in the number of sequencing reads in the STAD and other cohorts, as
      opposed to differential driver biology. Using strict filtering criteria, we found
      similar behavior in four other genes across TCGA cohorts, with each gene
      exhibiting systematic sequencing depth issues affecting the ability to call
      mutations. We identified the culprit as the choice of exome capture kit, as kit
      choice was highly associated with the set of genes that have insufficient reads
      to call a mutation. Overall, we found that thousands of samples across all
      cohorts are subject to some capture kit problems. For example, for the 6353
      samples using the Broad Institute's Custom capture kit there are undercalling
      biases for at least 4833 genes. False negative mutation calls at these genes may
      obscure biological similarities between tumor types and other important cancer
      driver effects in TCGA datasets.

PMID- 30281679
TI  - Developing a model to predict unfavourable treatment outcomes in patients with
      tuberculosis and human immunodeficiency virus co-infection in Delhi, India.
AB  - BACKGROUND: Tuberculosis (TB) patients with human immunodeficiency virus (HIV) co
      infection have worse TB treatment outcomes compared to patients with TB alone.
      The distribution of unfavourable treatment outcomes differs by socio-demographic
      and clinical characteristics, allowing for early identification of patients at
      risk. OBJECTIVE: To develop a statistical model that can provide individual
      probabilities of unfavourable outcomes based on demographic and clinical
      characteristics of TB-HIV co-infected patients. METHODOLOGY: We used data from
      all TB patients with known HIV-positive test results (aged >=15 years) registered
      for first-line anti-TB treatment (ATT) in 2015 under the Revised National TB
      Control Programme (RNTCP) in Delhi, India. We included variables on demographics
      and pre-treatment clinical characteristics routinely recorded and reported to
      RNTCP and the National AIDS Control Organization. Binomial logistic regression
      was used to develop a statistical model to estimate probabilities of unfavourable
      TB treatment outcomes (i.e., death, loss to follow-up, treatment failure,
      transfer out of program, and a switch to drug-resistant regimen). RESULTS: Of
      55,260 TB patients registered for ATT in 2015 in Delhi, 928 (2%) had known HIV
      positive test results. Of these, 816 (88%) had drug-sensitive TB and were >=15
      years. Among 816 TB-HIV patients included, 157 (19%) had unfavourable TB
      treatment outcomes. We developed a model for predicting unfavourable outcomes
      using age, sex, disease classification (pulmonary versus extra-pulmonary), TB
      treatment category (new or previously treated case), sputum smear grade, known
      HIV status at TB diagnosis, antiretroviral treatment at TB diagnosis, and CD4
      cell count at ATT initiation. The chi-square p-value for model calibration
      assessed using the Hosmer-Lemeshow test was 0.15. The model discrimination,
      measured as the area under the receiver operator characteristic (ROC) curve, was
      0.78. CONCLUSION: The model had good internal validity, but should be validated
      with an independent cohort of TB-HIV co-infected patients to assess its
      performance before clinical or programmatic use.

PMID- 30281680
TI  - Clinical-epidemiological and laboratory profiles of severe Schistosomiasis
      mansoni infections at a university hospital.
AB  - OBJECTIVE: Schistosomiasis remains a public health problem. This was a
      descriptive and retrospective study of 42 patients with a severe form of
      schistosomiasis who were admitted to the outpatient clinic of the Faculdade de
      Medicina da Universidade de Sao Paulo, Sao Paulo, in Sao Paulo, Brazil. METHODS:
      A data collection questionnaire was designed from the patient charts, and the
      following variables were evaluated: age, sex, place of birth, occupation, signs
      and symptoms of schistosomiasis, data from laboratory and imaging examinations,
      data regarding treatment outcomes, and the existence of comorbidities.
      Statistical analysis was carried out using Statistical Package for the Social
      Sciences 15.0 and Microsoft Excel 2003 software. The significance levels of the
      tests were fixed, accepting 5% type 1 error (alpha=0.05). Since this was a
      retrospective observational study, not all data were available for analysis.
      RESULTS: The mean age of the patients was 48.24 years; 57.1% were male.
      Statistically significant associations were observed between splenomegaly and
      thrombocytopenia (p=0.004) and between splenomegaly and leukopenia (p=0.046);
      however, only 4.5% of the patients had esophageal hemorrhage. Some patients
      received a specific treatment; of those, 42% took praziquantel, and 35.4% took
      oxamniquine. Nonspecific drug therapy was given as follows: 65% received
      propranolol, 90% omeprazole, and 43.6% aluminum hydroxide. The other treatments
      were as follows: 92.9% of patients underwent endoscopic treatment, 85% received
      sclerotherapy, and 62.5% used elastic bandages. CONCLUSION: This preliminary
      study presents a multidisciplinary outpatient follow-up associated with
      endoscopic and drug treatments that may be effective at preventing bleeding.

PMID- 30281681
TI  - Relationship between the biomechanical properties of the cornea and anterior
      segment measurements.
AB  - OBJECTIVE: To evaluate the relationship of biomechanical properties, corneal
      hysteresis and corneal resistance factor with age, sex and various corneal
      parameters measured with a Pentacam in normal subjects. METHODS: A total of 226
      eyes from 113 patients were enrolled in this study. The subjects underwent Ocular
      Response Analyzer and Pentacam evaluations. A varying-intercept multilevel
      regression was implemented using Bayesian inference. The predictor variables were
      age, sex, central corneal thickness, corneal volume at a 7-mm diameter, anterior
      chamber angle and volume, anterior chamber depth, mean radius of the corneal
      curvature and corneal astigmatism. RESULTS: Corneal hysteresis ranged from 5.5 to
      14.8 mmHg (mean 10.42+/-1.74 mmHg), and the corneal resistance factor ranged from
      5.7 to 15.5 mmHg (mean 10.23+/-1.88 mmHg). No predictor variable other than
      gender and central corneal thickness had a significant correlation with either
      corneal hysteresis or corneal resistance factor. Corneal hysteresis was
      positively associated with female sex and with central corneal thickness, and
      corneal resistance factor was positively associated with central corneal
      thickness. CONCLUSION: Despite the associations found, only a small fraction of
      the variance in biomechanical measurements could be explained by the descriptors
      that were evaluated, indicating the influence of other corneal aspects on the
      biomechanical characteristics.

PMID- 30281682
TI  - Using UV light for adhesive remnant removal after debonding of orthodontic
      accessories.
AB  - The objective of this study was to assess the effect of a UV light-based
      auxiliary illumination on adhesive remnant (AR) removal after orthodontic
      debonding. Sixty human molars were divided according to the adhesive used for
      bonding: O-opaque; LF-low fluorescence; and HF-high fluorescence. After
      debonding, the teeth were subdivided according to the AR removal method: No UV
      light or With UV light. After AR removal, the teeth were polished. Direct visual
      analysis, scanning electron microscopy (SEM) and time quantification for AR
      removal analyses were performed (Fisher-Freeman-Halton, Fisher's exact, chi
      square trend, ANOVA, and independent t-tests; alpha = 5%). Concerning the
      adhesives, there was no significant difference among direct visual, SEM and time
      analyses for AR removal (p >= 0.05). Regarding AR removal methods, a similarity
      among the subgroups was verified for direct visual and SEM analyses (p>=0.05).
      However, a significant trend was verified for the with UV light method to produce
      greater marks, and the no UV light method, to produce a greater rate of samples
      with AR before polishing (p = 0.015). AR removal with light was significantly
      quicker in comparison with the no UV light method (p < 0.0001). The use of UV
      light may aid orthodontists in removing AR more thoroughly and in less time.
      However, they should receive special training to apply this technology, and
      should never dismiss the final polishing procedure.

PMID- 30281683
TI  - Systemic melatonin application increases bone formation in mandibular distraction
      osteogenesis.
AB  - This study aimed to investigate the effects of different doses of systemic
      melatonin application on new bone formation during mandibular distraction
      osteogenesis (DO) in rats. Mandibular DO was performed on 30 adult female Sprague
      Dawley rats, which were randomly divided into three groups: control group (CNT),
      melatonin dose 1 (MLT-D1), and melatonin dose 2 (MLT-D2). A five-day latent
      waiting period and a ten-day distraction phase followed the surgery. After the
      surgery, rats from the MLT-D1 and MLT-D2 groups received 25 and 50 mg/kg
      melatonin, respectively, at 7, 14, 21, 28, and 35 days. The animals were
      euthanised 28 days after distraction, i.e. at 43 days after surgery. Histological
      and histomorphometric analyses revealed that the distracted bone area was
      completely filled with new bone formation in all three groups. The MLT-D2 group
      exhibited the most new bone formation, followed by MLT-D1 and CNT. The melatonin
      groups had more osteoclasts than the CNT (p < 0.05). The number of osteoblasts
      was higher in the melatonin groups than in the CNT group, and the MLT-D2 had more
      osteoclasts than the MLT-D1 group (p < 0.05). Finally, the osteopontin (OPN) and
      vascular endothelial growth factor (VEGF) levels were higher in the melatonin
      groups than in the CNT group, and the MLT-D2 had higher OPN and VEGF levels than
      the MLT-D1 (p < 0.05). This study suggests that systemic melatonin application
      could increase new bone formation in DO.

PMID- 30281684
TI  - Factors Associated with Inadequate Management of Antiplatelet Agents in
      Perioperative Period of Non-Cardiac Surgeries.
AB  - BACKGROUND: The current guidelines dispose recommendations to manage antiplatelet
      agents in the perioperative period; however, the daily medical practices lack
      standardization. OBJECTIVES: To asses factors associated with inadequate
      management of antiplatelet agents in the perioperative period of non-cardiac
      surgeries. METHODS: Cross-sectional Study conducted in hospital from October 2014
      to October 2016. The study dependent variable was a therapy that did not comply
      with the recommendations in the Brazilian Association of Cardiology (SBC)
      guidelines. The independent variables included some characteristics, the people
      in charge of the management and causes of lack of adherence to those guidelines.
      Variables were included in the multivariate model. Analysis was based on the odds
      ratio (OR) value and its respective 95% confidence interval (CI) estimated by
      means of logistic regression with 5% significance level. RESULTS: The sample was
      composed of adult patients submitted to non-cardiac surgeries and who would use
      acetylsalicylic acid (aspirin) or clopidogrel (n = 161). The management failed to
      comply with the recommendations in the guidelines in 80.75% of the sample.
      Surgeons had the highest number of noncomplying orientations (n = 63). After
      multivariate analysis it was observed that patients with a higher level of
      schooling (OR = 0.24; CI95% 0.07-0.78) and those with a previous episode of acute
      myocardial infarction (AMI) (OR = 0.18; CI95% 0.04-0.95) had a higher probability
      of using a therapy complying with the guidelines. CONCLUSION: Positive
      association between patients' schooling level, or those with a history of
      previous AMI, with management of the use of aspirin and clopidogrel in the
      perioperative period of non-cardiac surgeries. However, diverging conducts stress
      the need of having internal protocol defined.

PMID- 30281685
TI  - Effects of Rosuvastatin on Apolipoprotein J in Balloon-Injured Carotid Artery in
      Rats.
AB  - BACKGROUND: Restenosis after percutaneous coronary intervention in coronary heart
      disease remains an unsolved problem. Clusterin (CLU) (or Apolipoprotein [Apo] J)
      levels have been reported to be elevated during the progression of
      postangioplasty restenosis and atherosclerosis. However, its role in neointimal
      hyperplasia is still controversial. OBJECTIVE: To elucidate the role Apo J in
      neointimal hyperplasia in a rat carotid artery model in vivo with or without
      rosuvastatin administration. METHODS: Male Wistar rats were randomly divided into
      three groups: the control group (n = 20), the model group (n = 20) and the statin
      intervention group (n = 32). The rats in the intervention group were given 10mg
      /kg dose of rosuvastatin. A 2F Fogarty catheter was introduced to induce vascular
      injury. Neointima formation was analyzed 1, 2, 3 and 4 weeks after balloon
      injury. The level of Apo J was measured by real-time PCR, immunohistochemistry
      and western blotting. RESULTS: Intimal/medial area ratio (intimal/medial, I/M)
      was increased after balloon-injury and reached the maximum value at 4weeks in the
      model group; I/M was slightly increased at 2 weeks and stopped increasing after
      rosuvastatin administration. The mRNA and protein levels of Apo J in carotid
      arteries were significantly upregulated after rosuvastatin administration as
      compared with the model group, and reached maximum values at 2 weeks, which was
      earlier than in the model group (3 weeks). CONCLUSION: Apo J served as an acute
      phase reactant after balloon injury in rat carotid arteries. Rosuvastatin may
      reduce the neointima formation through up-regulation of Apo J. Our results
      suggest that Apo J exerts a protective role in the restenosis after balloon
      injury in rats.

PMID- 30281686
TI  - Usefulness of preoperative venography in patients with cardiac implantable
      electronic devices submitted to lead replacement or device upgrade procedures.
AB  - BACKGROUND: Venous obstructions are common in patients with transvenous cardiac
      implantable electronic devices, but they rarely cause immediate clinical
      problems. The main consequence of these lesions is the difficulty in obtaining
      venous access for additional leads implantation. OBJECTIVES: We aimed to assess
      the prevalence and predictor factors of venous lesions in patients referred to
      lead reoperations, and to define the role of preoperative venography in the
      planning of these procedures. METHODS: From April 2013 to July 2016, contrast
      venography was performed in 100 patients referred to device upgrade, revision and
      lead extraction. Venous lesions were classified as non-significant (< 50%),
      moderate stenosis (51-70%), severe stenosis (71-99%) or occlusion (100%).
      Collateral circulation was classified as absent, discrete, moderate or
      accentuated. The surgical strategy was defined according to the result of the
      preoperative venography. Univariate analysis was used to investigate predictor
      factors related to the occurrence of these lesions, with 5% of significance
      level. RESULTS: Moderate venous stenosis was observed in 23%, severe in 13% and
      occlusions in 11%. There were no significant differences in relation to the
      device side or the venous segment. The usefulness of the preoperative venography
      to define the operative tactic was proven, and in 99% of the cases, the
      established surgical strategy could be performed according to plan. CONCLUSIONS:
      The prevalence of venous obstruction is high in CIED recipients referred to
      reoperations. Venography is highly indicated as a preoperative examination for
      allowing the adequate surgical planning of procedures involving previous
      transvenous leads.

PMID- 30281687
TI  - Anger and Coronary Artery Disease in Women Submitted to Coronary Angiography: A
      48-Month Follow-Up.
AB  - BACKGROUND: Anger control was significantly lower in patients with coronary
      artery disease (CAD), regardless of traditionally known risk factors, occurrence
      of prior events or other anger aspects in a previous study of our research group.
      OBJECTIVE: To assess the association between anger and CAD, its clinical course
      and predictors of low anger control in women submitted to coronary angiography.
      METHODS: This is a cohort prospective study. Anger was assessed by use of
      Spielberger's State-Trait Anger Expression Inventory (STAXI). Women were
      consecutively scheduled to undergo coronary angiography, considering CAD
      definition as >= 50% stenosis of one epicardial coronary artery. RESULTS: During
      the study, 255 women were included, being divided into two groups according to
      their anger control average (26.99). Those with anger control below average were
      younger and had a family history of CAD. Patients were followed up for 48 months
      to verify the occurrence of major cardiovascular events. CONCLUSION: Women with
      CAD undergoing coronary angiography had lower anger control, which was associated
      with age and CAD family history. On clinical follow-up, event-free survival did
      not significantly differ between patients with anger control above or below
      average.

PMID- 30281688
TI  - Prognostic Differences between Men and Women with Acute Coronary Syndrome. Data
      from a Brazilian Registry.
AB  - BACKGROUND: Gender-related differences have been reported in patients with acute
      coronary syndrome. The description of this comparative finding in a Brazilian
      registry has not yet been documented. OBJECTIVE: To compare male vs. female
      patients regarding the baseline characteristics, coronary findings, treatment and
      in-hospital and long-term prognosis. METHODS: This is a retrospective,
      multicenter and observational study that included 3,745 patients (2,437 males and
      1,308 females) between May 2010 and May 2015. The primary in-hospital outcome was
      all-cause mortality. The secondary outcome consisted of combined events
      (cardiogenic shock, reinfarction, death, stroke and bleeding). The comparison
      between groups was performed using the chi-square and the t test, considering p <
      0.05 as significant. In the long term, mortality and combined events were
      assessed using the Kaplan-Meier method, with a mean follow-up of 8.79 months.
      RESULTS: The mean age was 60.3 years for males and 64.6 for females (p < 0.0001).
      The most prevalent risk factor was systemic arterial hypertension in 72.9% of the
      women and 67.8% of the men (p = 0.001). Percutaneous coronary intervention was
      carried out in 44.9% of the males and 35.4% of the females (p < 0.0001), and
      coronary artery bypass grafting (CABG) was performed in 17% of the males and
      11.8% of females (p < 0.0001), with a higher prevalence of three-vessel coronary
      artery disease in males (27.3% vs. 16.2%, p < 0.0001). Approximately 79.9% of the
      female patients received a diagnosis of acute coronary syndrome without ST
      segment elevation, while in the male patients, this diagnosis was attained in
      71.5% (p < 0.0001). No significant differences were observed between the groups
      in the short and long term, regarding both mortality and the combined events.
      CONCLUSION: Several gender-related differences were observed in patients with
      acute coronary syndrome regarding the demographic characteristics, coronary
      artery disease pattern and implemented treatment. However, the prognostic
      evolution was similar between the groups.

PMID- 30281689
TI  - Comparison of Cardiac and Vascular Parameters in Powerlifters and Long-Distance
      Runners: Comparative Cross-Sectional Study.
AB  - BACKGROUND: Cardiac remodeling is a specific response to exercise training and
      time exposure. We hypothesized that athletes engaging for long periods in high
      intensity strength training show heart and/or vascular damage. OBJECTIVE: To
      compare cardiac characteristics (structure and function) and vascular function
      (flow-mediated dilation [FMD] and peripheral vascular resistance [PVR]) in
      powerlifters and long-distance runners. METHODS: We evaluated 40 high-performance
      athletes (powerlifters [PG], n = 16; runners [RG], n = 24) and assessed heart
      structure and function (echocardiography), systolic and diastolic blood pressure
      (SBP/DBP), FMD, PVR, maximum force (squat, bench press, and deadlift), and
      maximal oxygen uptake (spirometry). A Student's t Test for independent samples
      and Pearson's linear correlation were used (p < 0.05). RESULTS: PG showed higher
      SBP/DBP (p < 0.001); greater interventricular septum thickness (p < 0.001),
      posterior wall thickness (p < 0.001) and LV mass (p < 0.001). After adjusting LV
      mass by body surface area (BSA), no difference was observed. As for diastolic
      function, LV diastolic volume, wave E, wave e', and E/e' ratio were similar for
      both groups. However, LA volume (p = 0.016) and BSA-adjusted LA volume were lower
      in PG (p < 0.001). Systolic function (end-systolic volume and ejection fraction),
      and FMD were similar in both groups. However, higher PVR in PG was observed (p =
      0.014). We found a correlation between the main cardiovascular changes and total
      weight lifted in PG. CONCLUSIONS: Cardiovascular adaptations are dependent on
      training modality and the borderline structural cardiac changes are not
      accompanied by impaired function in powerlifters. However, a mild increase in
      blood pressure seems to be related to PVR rather than endothelial function.

PMID- 30281690
TI  - Arterial Stiffness Use for Early Monitoring of Cardiovascular Adverse Events due
      to Anthracycline Chemotherapy in Breast Cancer Patients. A Pilot Study.
AB  - BACKGROUND: Chemotherapy with doxorubicin and cyclophosphamide, although
      efficient for treating breast cancer, is associated with cardiovascular
      complications. Recent studies seek to identify methods that can early detect
      cardiological and vascular changes as a strategy to decrease the incidence of
      cardiovascular comorbidities. OBJECTIVE: To evaluate the role of arterial
      stiffness measurement in the monitoring of doxorubicin and cyclophosphamide
      induced cardiotoxicity in breast cancer patients. METHODS: Prospective
      longitudinal study in 24 breast cancer patients undergoing treatment with
      doxorubicin and cyclophosphamide. Patients underwent an indirect evaluation of
      arterial stiffness through non-invasive measurement of hemodynamic parameters
      such as pulse wave velocity with the Mobil-O-Graph(r) 24H PWA device at three
      different times of the chemotherapy treatment (pre-chemotherapy, after the first
      and the fourth cycle). The left ventricular ejection fraction was also evaluated
      by Doppler echocardiography (pre-chemotherapy and after the fourth chemotherapy
      cycle). Data were considered significant when p <= 0.05. RESULTS: Patients had a
      mean age of 52.33 +/- 8.85 years and body mass index of 31 +/- 5.87 kg/m2. There
      was no significant difference between the hemodynamic parameters evaluated by the
      oscillometric method or in the left ventricular ejection fraction in the
      different evaluated periods. CONCLUSION: Evaluations of arterial stiffness by
      oscillometry and measurement of left ventricular ejection fraction by Doppler
      echocardiography showed equivalence in the values found, suggesting that the
      evaluation method of arterial stiffness studied could be used as a marker for
      cardiovascular adverse events associated with doxorrubicin-based chemotherapy
      drugs.

PMID- 30281691
TI  - Validation of the Brazilian-Portuguese Version of a Short Questionnaire to Assess
      Knowledge in Cardiovascular Disease Patients (CADE-Q SV).
AB  - BACKGROUND: Patient education is an essential part of cardiovascular patients'
      care targeting self-management behavior to reduce risk factors and subsequent
      events. Herein, a short and reliable tool to assess patients' knowledge in Brazil
      is warranted. OBJECTIVES: To translate, culturally-adapt and psychometrically
      validate the Portuguese version of the Coronary Artery Disease Education
      Questionnaire Short Version (CADE-Q SV). METHODS: The Portuguese CADE-Q SV -
      translated and culturally-adapted - was reviewed by five bilingual experts in
      cardiovascular disease. This version was then pre-tested in 21 patients, and
      clarity of items was checked using a Likert-type scale ranging from 1 = not clear
      to 10 = very clear. It was then psychometrically tested in 200 cardiovascular
      patients (41%women; mean age = 58.4 +/- 11.6 years old). The internal consistency
      was assessed using Kuder-Richardson-20 (KR-20) and Cronbach's alpha, test-retest
      reliability through intraclass correlation coefficient (ICC), factor structure
      using confirmatory factor analysis, and construct validity regarding educational
      level, family income, and time of diagnosis. RESULTS: All questions were
      considered clear by patients (clarity range:7.8-9.6). KR-20 was 0.70. All ICC
      values were > 0.70. Factor analysis revealed 6 factors, all internally
      consistent. Construct validity was supported by significant differences in total
      scores by educational level and family income (p < 0.001). The overall mean was
      13.08 +/- 2.61. The area with the highest knowledge was risk factors and the
      lowest was psychosocial risk. CONCLUSIONS: The Portuguese CADE-SV was
      demonstrated to have good validity and reliability. This tool can be applicable
      in clinical and research settings, assessing cardiovascular patients' knowledge
      as part of an education programming.

PMID- 30281692
TI  - Fractional Flow Reserve-Guided Strategy in Acute Coronary Syndrome. A Systematic
      Review and Meta-Analysis.
AB  - BACKGROUND: There are limited data on the prognosis of deferral of lesion
      treatment in patients with acute coronary syndrome (ACS) based on fractional flow
      reserve (FFR). OBJECTIVES: To provide a systematic review of the current evidence
      on the prognosis of deferred lesions in ACS patients compared with deferred
      lesions in non-ACS patients, on the basis of FFR. METHODS: We searched Medline,
      EMBASE, and the Cochrane Library for studies published between January 2000 and
      September 2017 that compared prognosis of deferred revascularization of lesions
      on the basis of FFR in ACS patients compared with non-ACS patients. We conducted
      a pooled relative risk meta-analysis of four primary outcomes: mortality,
      cardiovascular (CV) mortality, myocardial infarction (MI) and target-vessel
      revascularization (TVR). RESULTS: We identified 7 studies that included a total
      of 5,107 patients. A pooled meta-analysis showed no significant difference in
      mortality (relative risk [RR] = 1.44; 95% CI, 0.9-2.4), CV mortality (RR = 1.29;
      95% CI = 0.4-4.3) and TVR (RR = 1.46; 95% CI = 0.9-2.3) after deferral of
      revascularization based on FFR between ACS and non-ACS patients. Such deferral
      was associated with significant additional risk of MI (RR = 1.83; 95% CI = 1.4
      2.4) in ACS patients. CONCLUSION: The prognostic value of FFR in ACS setting is
      not as good as in stable patients. The results demonstrate an increased risk of
      MI but not of mortality, CV mortality, and TVR in ACS patients.

PMID- 30281693
TI  - Association Between Increased Levels of Cystatin C and the Development of
      Cardiovascular Events or Mortality: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Cystatin C seems promising for evaluating the risk of cardiovascular
      events and mortality. OBJECTIVE: To evaluate the association between high levels
      of cystatin C and the development of cardiovascular events or mortality. METHODS:
      The articles were selected in the Medline/PubMed, Web of Science, and Scielo
      databases. The eligibility criteria were prospective cohort observational trials
      that assessed the association of high serum levels of cystatin C with the
      development of cardiovascular events or mortality in individuals with normal
      renal function. Only studies that evaluated the mortality outcome compared the
      fourth with the first quartile of cystatin C and performed multivariate Cox's
      proportional hazard regression analysis were included in the meta-analysis. A p
      value < 0,05 was considered significant. RESULTS: Among the 647 articles found,
      12 were included in the systematic review and two in the meta-analysis. The risk
      of development of adverse outcomes was assessed by eight studies using the hazard
      ratio. Among them, six studies found an increased risk of cardiovascular events
      or mortality. The multivariate regression analysis was performed by six studies,
      and the risk of developing adverse outcomes remained significant after the
      analysis in four of these studies. The result of the meta-analysis [HR = 2.28
      (1.70-3.05), p < 0.001] indicated that there is a significant association between
      high levels of cystatin C and the risk of mortality in individuals with normal
      renal function. CONCLUSION: There is a significant association between high
      levels of cystatin C and the development of cardiovascular events or mortality in
      individuals with normal renal function.

PMID- 30281694
TI  - Mortality for Critical Congenital Heart Diseases and Associated Risk Factors in
      Newborns. A Cohort Study.
AB  - BACKGROUND: Congenital heart diseases are the most common type of congenital
      defects, and account for more deaths in the first year of life than any other
      condition, when infectious etiologies are ruled out. OBJECTIVES: To evaluate
      survival, and to identify risk factors in deaths in newborns with critical and/or
      complex congenital heart disease in the neonatal period. METHODS: A cohort study,
      nested to a randomized case-control, was performed, considering the Confidence
      Interval of 95% (95% CI) and significance level of 5%, paired by gender of the
      newborn and maternal age. Case-finding, interviews, medical record analysis,
      clinical evaluation of pulse oximetry (heart test) and Doppler echocardiogram
      were performed, as well as survival analysis, and identification of death-related
      risk factors. RESULTS: The risk factors found were newborns younger than 37 weeks
      (Relative Risk - RR: 2.89; 95% CI [1.49-5.56]; p = 0.0015), weight of less than
      2,500 grams (RR: 2.33 [; 95% CI 1.26-4.29]; p = 0.0068), occurrence of twinning
      (RR: 11.96 [95% CI 1.43-99.85]; p = 0.022) and presence of comorbidity (RR: 2.27
      [95% CI 1.58-3.26]; p < 0.0001). The incidence rate of mortality from congenital
      heart disease was 81 cases per 100,000 live births. The lethality attributed to
      critical congenital heart diseases was 64.7%, with proportional mortality of
      12.0%. The survival rate at 28 days of life decreased by almost 70% in newborns
      with congenital heart disease. The main cause of death was cardiogenic shock.
      CONCLUSION: Preterm infants with low birth weight and comorbidities presented a
      higher risk of mortality related to congenital heart diseases. This cohort was
      extinguished very quickly, signaling the need for greater investment in
      assistance technology in populations with this profile.

PMID- 30281695
TI  - Independent Predictors of Late Presentation in Patients with ST-Segment Elevation
      Myocardial Infarction.
AB  - BACKGROUND: In patients with acute ST-segment elevation myocardial infarction
      (STEMI), the time elapsed from symptom onset to receiving medical care is one of
      the main mortality predictors. OBJECTIVE: To identify independent predictors of
      late presentation in patients STEMI representative of daily clinical practice.
      METHODS: All patients admitted with a diagnosis of STEMI in a reference center
      between December 2009 and November 2014 were evaluated and prospectively followed
      during hospitalization and for 30 days after discharge. Late presentation was
      defined as a time interval > 6 hours from chest pain onset until hospital
      arrival. Multiple logistic regression analysis was used to identify independent
      predictors of late presentation. Values of p < 0.05 were considered statistically
      significant. RESULTS: A total of 1,297 patients were included, with a mean age of
      60.7 +/- 11.6 years, of which 71% were males, 85% Caucasians, 72% had a mean
      income lower than five minimum wages and 66% had systemic arterial hypertension.
      The median time of clinical presentation was 3.00 [1.40-5.48] hours, and
      approximately one-quarter of the patients had a late presentation, with their
      mortality being significantly higher. The independent predictors of late
      presentation were Black ethnicity, low income and diabetes mellitus, and a
      history of previous heart disease was a protective factor. CONCLUSION: Black
      ethnicity, low income and diabetes mellitus are independent predictors of late
      presentation in STEMI. The identification of subgroups of patients prone to late
      presentation may help to stimulate prevention policies for these high-risk
      individuals.

PMID- 30281696
TI  - Organization of the cancer network in SUS: evolution of the care model.
AB  - In the current context of epidemiological transition, demographic changes,
      changes in consumption and lifestyle habits, and pressure on care costs and
      organized health systems for acute conditions, the Integrated Care Model by
      Shortell has become a conceptual reference in the search for new methods to
      manage chronic conditions by focusing on the health conditions of a given
      population that must be addressed by a set of institutions organized into
      networks. Within the last 15 years, cancer has gone from the third- to the second
      leading cause of death in the State of Sao Paulo and has shown a gradual increase
      in the number of new cases; it has thus become a relevant issue for public health
      and health management. The model adopted by the State for the organization of the
      cancer care network was the motivation for this study, which aimed to evaluate
      the evolution of the model of care for cancer patients within the Unified Health
      System (Sistema Unico de Saude) based on the integrated care model. Since 1993,
      the year that cancer was first considered highly complex in the Sistema Unico de
      Saude by the Ministry of Health, it has been possible to observe a progressive
      orientation towards the integral and integrated care of patients with cancer. In
      the State of Sao Paulo, the active participation of qualified service providers
      through a Technical Reference Committee showed that experts could contribute to
      the definition of public policies, thereby providing a technical base for
      decision making and contributing to the development of clinical management.

PMID- 30281697
TI  - Academic health centers: integration of clinical research with healthcare and
      education. Comments on a workshop.

PMID- 30281698
TI  - Introduction of robotic surgery for endometrial cancer into a Brazilian cancer
      service: a randomized trial evaluating perioperative clinical outcomes and costs.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical outcome and
      costs after the implementation of robotic surgery in the treatment of endometrial
      cancer, compared to the traditional laparoscopic approach. METHODS: In this
      prospective randomized study from 2015 to 2017, eighty-nine patients with
      endometrial carcinoma that was clinically restricted to the uterus were
      randomized in robotic surgery (44 cases) and traditional laparoscopic surgery (45
      cases). We compared the number of retrieved lymph nodes, total time of surgery,
      time of each surgical step, blood loss, length of hospital stay, major and minor
      complications, conversion rates and costs. RESULTS: The ages of the patients
      ranged from 47 to 69 years. The median body mass index was 31.1 (21.4-54.2) in
      the robotic surgery arm and 31.6 (22.9-58.6) in the traditional laparoscopic arm.
      The median tumor sizes were 4.0 (1.5-10.0) cm and 4.0 (0.0-9.0) cm in the robotic
      and traditional laparoscopic surgery groups, respectively. The median total
      numbers of lymph nodes retrieved were 19 (3-61) and 20 (4-34) in the robotic and
      traditional laparoscopic surgery arms, respectively. The median total duration of
      the whole procedure was 319.5 (170-520) minutes in the robotic surgery arm and
      248 (85-465) minutes in the traditional laparoscopic arm. Eight major
      complications were registered in each group. The total cost was 41% higher for
      robotic surgery than for traditional laparoscopic surgery. CONCLUSIONS: Robotic
      surgery for endometrial cancer presented equivalent perioperative morbidity to
      that of traditional laparoscopic surgery. The duration and total cost of robotic
      surgery were higher than those of traditional laparoscopic surgery.

PMID- 30281699
TI  - Lessons and perspectives for applications of stochastic models in biological and
      cancer research.
AB  - The effects of randomness, an unavoidable feature of intracellular environments,
      are observed at higher hierarchical levels of living matter organization, such as
      cells, tissues, and organisms. Additionally, the many compounds interacting as a
      well-orchestrated network of reactions increase the difficulties of assessing
      these systems using only experiments. This limitation indicates that elucidation
      of the dynamics of biological systems is a complex task that will benefit from
      the establishment of principles to help describe, categorize, and predict the
      behavior of these systems. The theoretical machinery already available, or ones
      to be discovered to help solve biological problems, might play an important role
      in these processes. Here, we demonstrate the application of theoretical tools by
      discussing some biological problems that we have approached mathematically:
      fluctuations in gene expression and cell proliferation in the context of loss of
      contact inhibition. We discuss the methods that have been employed to provide the
      reader with a biologically motivated phenomenological perspective of the use of
      theoretical methods. Finally, we end this review with a discussion of new
      research perspectives motivated by our results.

PMID- 30281700
TI  - Treatment of patients with metastatic colorectal cancer and poor performance
      status: current evidence and challenges.
AB  - Patients with unresectable metastatic colorectal cancer live for a median of
      three years when treated with standard therapies. While the evidence guiding
      cancer-directed treatment of this disease comes from phase III trials that have
      mostly enrolled patients with good performance status, some patients present with
      poor clinical conditions. The best treatment for these patients remains to be
      determined. We performed a systematic review of the treatment outcomes of
      patients with metastatic colorectal cancer and poor performance status, defined
      as Eastern Cooperative Oncology Group performance status >=2. Eligible articles
      were prospective or retrospective studies or case reports published in English,
      Portuguese or Spanish. We searched PubMed, EMBASE, LILACS and the Cochrane
      Library from onset until October 2017 using specific keywords for each search. We
      found a total of 18 publications, mostly case reports and retrospective studies
      (14 articles). One was an uncontrolled prospective trial, two were observational
      studies and one was an individual patient meta-analysis. Although some studies
      suggested benefits in terms of symptomatic response with standard chemotherapy,
      with good safety profiles when dose-reduced regimens were administered, a true
      survival gain could not be demonstrated. The scientific evidence for treating
      metastatic colorectal cancer patients with poor performance status is scarce, and
      more studies evaluating treatment for this population are necessary since this
      condition is not uncommon in clinical practice, particularly in the public
      healthcare system and developing countries and among destitute populations.

PMID- 30281701
TI  - Clinical perspectives of PSMA PET/MRI for prostate cancer.
AB  - Prostate cancer imaging has become an important diagnostic modality for tumor
      evaluation. Prostate-specific membrane antigen (PSMA) positron emission
      tomography (PET) has been extensively studied, and the results are robust and
      promising. The advent of the PET/magnetic resonance imaging (MRI) has added
      morphofunctional information from the standard of reference MRI to highly
      accurate molecular information from PET. Different PSMA ligands have been used
      for this purpose including 68gallium and 18fluorine-labeled PET probes, which
      have particular features including spatial resolution, imaging quality and tracer
      biodistribution. The use of PSMA PET imaging is well established for evaluating
      biochemical recurrence, even at low prostate-specific antigen (PSA) levels, but
      has also shown interesting applications for tumor detection, primary staging,
      assessment of therapeutic responses and treatment planning. This review will
      outline the potential role of PSMA PET/MRI for the clinical assessment of PCa.

PMID- 30281703
TI  - Survival and prognosis of young adults with gastric cancer.
AB  - OBJECTIVES: Survival data for young adults (YA) with gastric cancer is
      conflicting and scarce in Brazil. The aim of this study was to compare the
      clinicopathological factors and survival rates of younger and older patients with
      gastric cancer. METHODS: Hospital registries for 294 gastric cancer patients from
      a reference cancer hospital in Sao Paulo, Brazil, were consulted for the
      retrieval of clinicopathological information and follow-up time. Patients were
      placed into the following groups: YA (<=40 years; N=71), older adult (OA: 41 to
      65 years; N=129) and elderly (E: >=66 years; N=94). Differences were assessed
      through Pearson's chi2 test, Kaplan-Meier analysis, Log rank test and Cox
      regression. RESULTS: More YA were diagnosed with advanced disease (clinical stage
      III/IV: 86.7% YA, 69.9% OA, and 67% E); however, fewer E patients underwent
      surgery (64.3% YA, 72.7% OA, and 52.4% E). The median overall survival among all
      patients was 16 months, and the overall survival rate was not significantly
      different among the age groups (p=0.129). There were no significant differences
      in the disease-free survival rate. Metastatic disease at diagnosis (HR=4.84;
      p<0.01) was associated with an increased hazard of death for YA. CONCLUSION:
      Overall survival was similar among age groups. Metastatic disease at diagnosis
      was the only factor associated with a poorer prognosis in YA. These results
      suggest that younger patients deserve special attention regarding the detection
      of early stage disease.

PMID- 30281702
TI  - Epidemiological science and cancer control.
AB  - Epidemiological methods are essential for the discovery of cancer risks and
      prognostic factors as well as for the evaluation of cancer prevention measures.
      In this review, we discuss epidemiological surveillance procedures for data
      collection and processing to guide and evaluate the consequences of anticancer
      efforts for populations, assess the identification of cancer risk factors,
      examine barriers to cancer screening and recommended rules for early diagnosis
      programs. Epidemiological studies have shown that hindrances to cancer
      information assessment are currently encountered in developing countries. Known
      cancer risk factors include social determinants, lifestyle factors, occupational
      exposures, infectious agents, and genetic and epigenetic alterations. Challenges
      remain in studying the effectiveness of cancer screening; screening can have
      detrimental effects, and few cancers clearly benefit from screening. Currently,
      epidemiology faces the challenge of dealing with distinct levels of data,
      including factors related to social status, lifestyle and genetics, to
      reconstruct the causal traits of cancer. Additionally, translating
      epidemiological knowledge into cancer control demands more implementation studies
      in the population.

PMID- 30281704
TI  - Clinical stage and histological type of the most common carcinomas diagnosed in
      young adults in a reference cancer hospital.
AB  - OBJECTIVES: Cancer in young adults represents a great challenge, both
      biologically and socially, and understanding the unique characteristics of
      neoplasms in this age group is important to improving care. We aimed to evaluate
      the most common carcinomas and their characteristics, such as histological type
      and clinical stage, in young adults in the largest cancer hospital in Latin
      America. METHODS: The hospital registry was consulted for the period between 2008
      and 2014. Young adults were defined as individuals aged 18 to 39 years, and older
      adults were defined as individuals aged 40 years and older. Differences between
      age groups were assessed through chi-square tests. RESULTS: Of the 39,389
      patients included, 3,821 (9.7%) were young adults. Among the young adults, the
      most frequent cancer types were the following: breast, lymph node, colorectal,
      thyroid, testicle, hematopoietic and reticuloendothelial, uterine cervix, brain,
      soft tissue and stomach; these sites accounted for 74.5% of the observed tumors.
      Breast, colorectal and stomach cancers were more frequently diagnosed at advanced
      stages in young adults than in older adults (p<0.001). The most common
      histological types were infiltrating ductal carcinoma (86.12%) for breast cancer,
      adenocarcinomas not otherwise specified (45.35%) for colorectal cancer, squamous
      cell carcinoma not otherwise specified (65.26%) for uterine cervix cancer, signet
      ring cell adenocarcinomas (49.32%) for stomach cancer and adenocarcinomas not
      otherwise specified (50.79%) for lung cancer. CONCLUSION: Young adults are
      diagnosed with cancer at more advanced stages, indicating that health
      professionals should be aware of cancer incidence in this age group. It is
      necessary to develop a better understanding of cancer in young adults and to
      implement dedicated health care strategies for these patients.

PMID- 30281705
TI  - Vaccine confidence and hesitancy in Brazil.
AB  - Despite the overall benefits of immunization, vaccine hesitancy has been a
      growing trend and has been associated with the resurgence of vaccine-preventable
      diseases. The aim of this study was to assess vaccine confidence and hesitancy in
      Brazil, as part of a wider project to map vaccine confidence globally. One
      thousand subjects were interviewed, either online or face-to-face, based on a
      general questionnaire regarding perceptions on vaccines and vaccination. Further
      exploratory questions were used with the subset of respondents who were parents
      of children aged under 5. Such questions extracted information regarding
      vaccination behavior, opinions on vaccination and government health services, and
      vaccine hesitancy. Reasons for hesitancy were classified as relating to
      confidence, convenience and/or complacency, and the population was also analyzed
      socio-demographically. The results showed that overall confidence in immunization
      was higher than confidence in family planning services, community health workers
      and emergency services. Seventy-six people reported hesitancy to vaccinate. The
      commonest reasons for hesitancy were issues with confidence (41.4%),
      efficacy/safety of the vaccine (25.5%) and concerns about adverse events (23.6%).
      The sociodemographic analysis revealed that vaccine hesitancy was associated with
      marital status, level of education and income. Despite overall vaccine confidence
      being high, a clear trend toward lower levels of confidence was associated with
      higher levels of hesitancy, which warrants on-going monitoring, due to the
      dynamic and changing nature of vaccine hesitancy.

PMID- 30281706
TI  - Effects of smoking on tooth loss among individuals under periodontal maintenance
      therapy: a systematic review and meta-analysis.
AB  - Dental mortality has been reported by longitudinal studies on periodontal
      maintenance therapy (PMT), but the independent effect of smoking on tooth loss
      (TL), adjusted for important confounding variables, has been poorly evaluated.
      This systematic review aimed to assess and analyze the isolated effect of smoking
      TL among individuals undergoing PMT. Electronic, manual, grey literature, and
      recent articles (from April 2018) were searched, with no restriction regarding
      language; respective dates of publication were included. Epidemiological clinical
      studies reporting TL data among smokers undergoing PMT in comparison to nonsmoker
      control groups were selected. Methodological quality was assessed using the
      Newcastle-Ottawa Scale. Meta-analysis was performed, as well as I2 heterogeneity
      and sensitivity tests. Evidence quality was assessed using GRADE (Grading of
      Recommendations, Assessment, Development and Evaluation). Eleven papers were
      included in the systematic review: four case-control and seven cohort studies.
      Ten out of the 11 studies concluded that smoking was an important risk factor for
      the occurrence of TL. Meta-analysis of four of the cohort studies found that
      smokers had 3.24 times the chance of occurrence of TL than nonsmokers undergoing
      PMT (95%CI: 1.33-7.90). Overall, studies' risk of bias was low. The quality of
      the scientific evidence moderately supports that smokers undergoing PMT have a
      greater chance of TL than nonsmokers.

PMID- 30281707
TI  - Zika: heterogeneity and history.

PMID- 30281708
TI  - Why social perception matters during disease outbreaks: looking at how
      individuals understand the Zika virus by self-reported history of infection.

PMID- 30281709
TI  - [A proposal for the creation of a system to monitor cases of malignant
      mesothelioma in Curitiba, Parana, Brazil].
AB  - The study proposes the creation of a system to monitor cases of malignant
      mesothelioma in the municipality of Curitiba, Parana State, Brazil, based on the
      Italian model. This diagnosis-type action-research project featured exploratory
      and planning phases conducted from July 2015 to May 2017. The following search
      tools were used: Hospital-Based Cancer Registries Integrator with specific
      morphologies for mesothelioma; Hospital-Based Cancer Registry with codes C38.4
      and C45 of the International Classification of Diseases, 10th revision, and/or
      records coded by the ICD-O with topographies C38 and C48; Population-Based Cancer
      Registry of the Curitiba Municipal Health Department, with the same codes. The
      study also identified, analyzed, and adapted to the Brazilian reality the model,
      questionnaires, and registry software for mesothelioma from Lombardy, Italy.
      Fifteen cases of mesothelioma were recorded in the Hospital-Based Cancer
      Registries Integrator. Two cases were recorded in the University Hospital-Based
      Cancer Registry and 16 in the Cancer Hospital. There were 317 cases recorded in
      the Population-Based Cancer Registry during the same period. Although some
      information was complete, data were lacking on patients' occupational history,
      thereby preventing the determination of a causal nexus. Given a predicted
      increase in cases of mesothelioma in the coming decades and the response to court
      cases, the implementation of registries has become essential to facilitate
      knowledge and follow-up on the determination of the causal link and specific
      sources of asbestos exposure in the country.

PMID- 30281710
TI  - Association between the employment status and the presence of depressive symptoms
      in men and women in Mexico.
AB  - This study aims to estimate the relationship between employment status and
      depressive symptoms among Mexican adults, as well as to explore its differential
      effect by gender. Cross-sectional study of 36,516 adults between 20 and 59 years
      of age taken from the 2012 Mexican National Health and Nutrition Survey.
      Depressive symptoms were evaluated using the Center for Epidemiologic Studies
      Depression Scale (CES-D), and the employment status was determined a week before
      the survey. Logistic regression models were stratified by gender and education
      level and adjusted by sociodemographic and health-related conditions to estimate
      the association between depressive symptoms and employment status. The prevalence
      of clinically depressive symptoms was 7.59% for men and 18.62% for women. In the
      case of men, those who were unemployed were more likely to present depressive
      symptoms (OR = 1.66; 95%CI: 1.08-2.55) than those who were working. For women,
      employment status is not associated with the presence of depressive symptoms,
      except in students (OR = 1.57; 95%CI: 1.02-2.43) compared with those who were
      working. In both genders, disability preventing one from working was associated
      with depressive symptoms. Although being employed has been reported to be
      associated with lower levels of psychiatric morbidity, the estimated effect is
      different for men and women. Occupational health policies should consider these
      conditions.

PMID- 30281711
TI  - Trends in mortality from chronic obstructive pulmonary disease in Rio de Janeiro
      and Porto Alegre, Brazil, 1980-2014.
AB  - OBJECTIVE: to analyze age-period-cohort (APC) effects on mortality from chronic
      obstructive pulmonary disease (COPD) in the municipalities of Porto Alegre, RS,
      and Rio de Janeiro, RJ, Brazil, between 1980 and 2014. METHODS: this was a time
      series study using corrected Mortality Information System (SIM) data; APC effects
      were estimated by Poisson regression, in relation to the 1935 cohort. RESULTS:
      relative risk (RR) of death due to COPD for males decreased in the most recent
      birth cohort (1970-1974) in Porto Alegre (RR=0.39; 95%CI 0.32;0.48) and Rio de
      Janeiro (RR=0.42; 95%CI 0.38;0.48); while among women an increase in risk of
      death due to COPD was observed in Rio de Janeiro in more recent cohorts (RR=1.41;
      95%CI 1.20;1.67). CONCLUSION: risk of death due to COPD decreased among men,
      while risk among women in Rio de Janeiro increased.

PMID- 30281712
TI  - Oral health status of pregnant and puerperal women in the municipality of Feira
      de Santana, at three different times between 2005 and 2015.
AB  - OBJECTIVE: to evaluate the oral health condition of pregnant/postpartum women
      attending public services in the city of Feira de Santana, BA, Brazil, at three
      different times between 2005 and 2015. METHODS: this is a study socioeconomic and
      demographic characteristics, health condition and health care, lifestyle and oral
      health status of 1,245 participants obtained from a database of three previous
      investigations: I Intervention Study (2005-2007); II Case-Control Study (2010
      2011); III Case-Control Study (2012-2015). RESULTS: comparing the three periods,
      the frequency of gingivitis (24.41% versus 8.90% versus 5.77%; p<0.01) and
      periodontitis (44.64% vs 9.16% vs 11.55%; p<0.01) was found to decrease; the
      worst dental conditions regarding the number of teeth present, healthy and
      extracted and the DMFT index were found in period III compared to period II.
      CONCLUSION: an improvement was seen in the participants' periodontal condition
      over time, which coincides with the implementation of policies pertaining to
      women's health, oral health and income redistribution in this city.

PMID- 30281713
TI  - Leukemia mortality trends in children and adolescents in Brazilian state
      capitals: 1980-2015.
AB  - OBJECTIVE: to analyze the temporal trend of leukemia mortality in children and
      adolescents under 20 years old, in Brazilian state capitals and Federal District,
      between 1980 and 2015. METHODS: this was a descriptive time series study; age
      standardized leukemia mortality rates were calculated; the Prais-Winsten
      regression model was used. RESULTS: leukemia mortality rates fell from 2.73 to
      1.58 per 100,000 inhabitants aged under 20 years in the period studied (annual
      percentage variation of -7.06%: 95%CI -8.61;5.49), with differences between
      capitals; there was a reduction in magnitude in all age groups - 0-4 years
      (9.17%: 95%CI -11.58;-6.69), 5-9 years (-9,27%: 95%CI -11.90;-6.56), 10-14 years
      (-4.86%: 95%CI -6.69;-3.00) and 15-19 years (-3.77%: 95%CI -5.22;-2.31).
      CONCLUSION: there was a falling trend in pediatric leukemia mortality rates,
      although it was unequal between the capitals, indicating the need for measures to
      minimize regional differences.

PMID- 30281714
TI  - Hospitalization for Ambulatory Care Sensitive Conditions in children under five
      years old in Santa Catarina State, Brazil, 2012: a descriptive study.
AB  - OBJECTIVE: to describe proportions and rates of hospitalization for Ambulatory
      Care Sensitive Conditions (ACSC) among children under 5 years old, in Santa
      Catarina State, Brazil, 2012. METHODS: this is a descriptive study using
      Brazilian National Health Service Hospital Information System (SIH/SUS) data,
      classified according to the Brazilian ACSC List. RESULTS: a total of 32,445
      children aged <5 years old were hospitalized, 25,7% of whom were ACSC cases,
      representing a rate of 20.1/1,000 inhabitants in the same age group; the main
      causes were infectious gastroenteritis and complications (26.7%), bacterial
      pneumonia (22.2%) and pulmonary diseases (16.9%); there was a higher
      hospitalization rate due to ACSC in males (21.1/1,000), and in children <1 year
      old (43.8/1,000). CONCLUSION: The results showed that the State of Santa Catarina
      had lower rates and proportions than those found in other Brazilian studies, even
      though ACSC were the cause of one quarter of hospitalizations in children aged <5
      years.

PMID- 30281715
TI  - Women screened for breast cancer: follow-up through Health Information Systems,
      Brazil, 2010-2012.
AB  - OBJECTIVE: to describe the two-years follow-up of women with screening
      mammography showing lesions suspected or highly suspected of malignancy in the
      city of Rio de Janeiro, Brazil. METHODS: this was a descriptive study of the care
      line using Health Information Systems (SIS) data on women who underwent screening
      mammography in the Brazilian National Health System (SUS) in the second half of
      2010. RESULTS: of the 206 women studied, 13.1% had their mammograms requested by
      Primary Health Centers; during follow-up 102 (49.5%) were identified on at least
      one SIS; of these, 12 had biopsy information, all of which was positive for
      breast cancer; 93 had treatment, one of whom had benign disease; 12 died from
      breast cancer; the proportion of women identified as having treatment was higher
      among those with suspected high malignancy and palpable lesions (p<0.01).
      CONCLUSION: information on the breast cancer care line was partially recovered
      through SIS records.

PMID- 30281716
TI  - Adolescence and Youth: an international perspective on public policies on health
      and living conditions.

PMID- 30281717
TI  - Mortality by road traffic accidents in adolescents and young people, Brazil, 1996
      2015: will we achieve SDG 3.6?
AB  - This paper aims to analyze the main characteristics of Road Traffic Accidents
      (RTA) mortality in Brazil for the period 1996-2015, focusing on the 10-29 years'
      age group. This is a two-step study consisting of (i) a bibliographic review on
      the topic of traffic violence in Brazil, and (ii) a study on RTA mortality in the
      Mortality Information System (SIM). The former situates the state of the art of
      scientific production on the theme and produces the theoretical reference for the
      analysis of the latter. During the period, about 39,000 people died by RTA, of
      which about 13,200 adolescents and young people died. The country should curb
      mortality to somewhere around 19,500/year and, among adolescents and young
      people, to 6,500/year to achieve SDG 3.6. With the establishment of the Brazilian
      Traffic Code (CTB), RTA mortality rate fell between 1997 and 2000. The rate
      increased in the subsequent decade. The focus on adolescents and young people
      help us understand that, in the post-CTB and Prohibition, male black and brown
      motorcyclists became the main victims. The literature provides data analysis and
      shows that reduction is currently submitted to an articulated discussion that
      involves worker's health, gender, employment, urban mobility and advertising
      policies. Concerning SDG, this means that achieving SDG 3.6 is a process that
      involves interacting with policies targeting other SDGs.

PMID- 30281718
TI  - The 2030 Agenda as a development tool for young people in Argentina.
AB  - Youth and adolescent populations constitute a critical set in global population.
      They are important to development agendas not for their quantity, but for other
      types of problem that favour the intergenerational reproduction of poverty and
      establish inequality gaps that accentuate processes of "de-institutionalisation"
      and "de-socialisation" of these populations and others: education systems
      insufficiently adapted to the current world of work or to the mass schooling of
      young people from vulnerable households; precarious labour markets, which many
      young people enter with poor qualifications; or socioenvironmental conditions
      that severely affect the health conditions of youth in marginal neighbourhoods.
      The 17 Sustainable Development Goals clearly signal the path forward for coming
      years, as well as highlighting the need for stronger, more innovative public
      policies to ensure "that no young people will be left behind". The 2030 Agenda
      represents a unique opportunity for the State, private sector, civil society and
      the international cooperation system to harness positive synergies to improve
      young people's quality of life.

PMID- 30281719
TI  - The production of victims as entrepreneurs of their social redemption: young
      people, control and involvement.
AB  - Drawing on the results of an ethnographic study and group interviews with young
      people and social project coordinators from favelasin Rio de Janeiro, this
      article discusses the association between youth and vulnerabilities and its
      possible consequences for the reinforcement of negative stereotypes of poor young
      people through discourses that emphasize self-management. It explores the notion
      of production of victims as entrepreneurs of their social redemption by promoting
      reflection on the use of the category involved in crime, disseminated in the
      common sense as a new form of criminal labeling. The article addresses material
      and symbolic investments in poor young people, beneficiaries of so-called social
      projects, reflecting on the maneuvers of meanings that veil the temporality of
      these initiatives, characterized by moralistic overtones of merit and salvation.
      The fear of dying or "remaining", of not finding a job, and a series of other
      fears are the focus of this reflection, which seeks to broaden the debate over
      institutional initiatives directed at young people.

PMID- 30281720
TI  - Global burden of disease among teenagers in Uruguay and its comparison with Latin
      America and the Caribbean.
AB  - INTRODUCTION: Adolescence is considered a healthy stage of life and therefore
      little studied. This study described mortality over time in teenagers in Uruguay
      and analysed the burden of disease at this stage of life by the measure of Years
      of Life Lost by Premature Death in Uruguay and by comparison with rates in Latin
      America and the Caribbean by sex, cause and sub-region. METHODOLOGY: Secondary
      data sources used were the national registry of deaths in Uruguay, the first
      Global Burden of Disease study in Uruguay and the information on the data
      visualisation page of the Institute of Metrics and Health Evaluation. Data were
      extracted by the authors and displayed in tables and graphs. RESULTS: Teenager
      mortality held roughly stable between 1997 and 2015. More years were lost to
      premature death among Uruguayan men, the main causes being traffic accidents,
      self-inflicted injuries and violence. The same behaviour occurs throughout the
      region. CONCLUSIONS: The social determinants of health connected with poverty and
      inequality play a role in the development of depression, risky and violent
      behaviour, which possibly explain the loss of years due to premature death in
      adolescence.

PMID- 30281721
TI  - An approach to suicide among adolescents and youth in Brazil.
AB  - This essay article examines suicide among young people in Brazil on the basis of
      Durkheim's classical approaches as revisited in current discussions of social
      integration networks. It presents arguments regarding the behaviour of suicide
      mortality rates in the light of classical public health assumptions as to social
      causality in processes of health and illness. The mortality rates, updated in
      line with international statistics, review of data in Brazilian studies and
      recent series for Brazil, reveal suicide "aptitudes" by age, sex and social
      group. The linear and non-linear nature of the trends are treated in the context
      of pathways in complex social systems. Current data were prospected in the
      Ministry of Health'sNational Mortality Information System and World Health
      Organisation databases. In this policy analysis study, a conceptual outline was
      built up from classical theory updated to the present-day context, analysis of
      data relevant to the study object and observation of target groups for
      comprehensive, inclusive policies. The results of this analysis reveal that
      adolescents and young people are highly liable to growing, sustained, high-impact
      vulnerability to suicide.

PMID- 30281722
TI  - Young population, sexually-transmitted diseases and rights. National and regional
      scenario in Argentina.
AB  - In the context of social and demographic studies of sexual and reproductive
      health, this paper discusses the situation of young people in Argentina,
      emphasizing the problems revolving around Sexually Transmitted Diseases (STDs)
      and the compliance with sexual rights. This work aims to study the calendars and
      characteristics of the onset of sexual life in young Argentinean people and to
      describe the current situation of knowledge, practices, and access related to
      sexual life. Based on data from the National Survey on Sexual and Reproductive
      Health ( 2013) we worked with the universe of young people between 15 and 29
      years of age (n = 2,084 women, n = 1,872 men, without weighting) and analyzed the
      differences in the calendars of the onset of sexual life, as well as the
      knowledge and prevention of STDs by gender sex, age groups, household income and
      geographical regions.A national scenario was found featuring marked tendencies in
      the calendars of first sexual intercourse by gender sex, as well as in the
      knowledge about STDs. However, the analysis by region and household income in
      each gendersex showed high heterogeneities, which would indicate certain
      limitations in the access to sexual education and the effective compliance of
      people's rights, as well as an increased risk to contracting STDs in specific
      social groups.

PMID- 30281723
TI  - Adolescent and youth health policies in the Portuguese-Brazilian context:
      specificities and approximations.
AB  - OBJECTIVE: To characterize the scientific production on adolescent health
      policies and programs in Brazil and Portugal in the period 2010-2017. METHOD:
      This is a literature review based on the Scoping Review method. The research
      guidingquestion was: "How is the scientific production on adolescent health
      policies and programs in Brazil and Portugal characterized?"Search was carried
      out in October 2017 on the BVS, EBSCO and Google Scholar platforms. RESULTS:
      Twenty-two studies were selected, namely, 17 Brazilian and 5 Portuguese. Seven
      cross-cutting thematic categories were identified, as follows: policy and program
      evaluation; health promotion and education; mental health; sexual and
      reproductive health; violence; oral health and nutritional health. We canconclude
      that, albeit in different social contexts, the themes reflect traditional areas
      of intervention of policies and programs, except for those arising from the
      phenomenon of structural violence, markedly present in the Brazilian reality.
      Also, the lack of emerging issues such as gender identities, migratory flows, and
      morbimortality from external causes reveal a possible care gap in policies and
      programs and a necessary field to be explored.

PMID- 30281724
TI  - National Policy for Comprehensive Health Care for Adolescents Deprived of
      Liberty: an analysis of its implementation.
AB  - The realization of the right to health of adolescents and young people deprived
      of their liberty in Brazil is a complex task that places us before health
      inequities and interventions on their social determinants of health. Therefore,
      this study sought to contribute to a discussion about the right to health of this
      population, based on the analysis of the implementation of the Comprehensive
      Healthcare Policy for Adolescent Offenders (PNAISARI). This is an analytical
      approach, using documentary analysis of legal frameworks and policy monitoring
      and evaluation data. In short, the results suggest that the policy strengthens
      the realization of the right to health of this population. However, its
      implementation must be promoted and qualified so that access to health care is,
      in fact, a reality in all states and municipalities.

PMID- 30281725
TI  - Rehabilitation doxa and practitioner judgment. An analysis of symbolic violence
      on health care provision in the Scottish prison system.
AB  - This paper presents an analysis of the symbolic conditions which govern health
      care provision in the Scottish prison system. The paper considers the wider
      context of Scottish prisons, where health care provision follows a similar
      structure both in juvenile and adult prisons. Our intention is to provoke a
      debate about the doxa (Bourdieu, 1977), which underlies decision making in
      respect of health care in prison, in a political environment where pragmatism,
      allied to the 'pathologisation' of social policies, health and criminal justice
      has been a hegemonic force.

PMID- 30281726
TI  - Challenges for public policies aimed at adolescence and youth based on the
      National Scholar Health Survey (PeNSE).
AB  - OBJECTIVE: to examine the problems and challenges facing implementation of
      policies for Brazilian adolescents, on the basis of narrative review of the
      findings of the National Survey of School Health (PeNSE). O objetivo do artigo e
      analisar os principais problemas e desafios para a implementacao de politicas
      publicas voltadas para a adolescencia brasileira a partir de revisao narrativa
      dos resultados da Pesquisa Nacional de Saude do Escolar (PeNSE). Ensaio teorico
      sobre politicas publicas produzido a partir de revisao narrativa das tres edicoes
      da PeNSE. Os artigos identificados foram categorizados em temas prioritarios para
      intervencao de politicas publicas. Tabagismo: estavel quanto ao cigarro e aumento
      de 18% de outros produtos do tabaco. Alcool: consumo regular caiu de 27,3% para
      23,2%. Drogas: aumento da experimentacao, a supervisao familiar mostrou-se
      protetora para uso de tabaco, alcool e drogas. Aumento de todos os indicadores de
      violencia. Predominio de habitos nao saudaveis: apenas 20% dos escolares praticam
      1 hora de atividade fisica ou mais diariamente. Sexualidade: reducao do uso
      preservativos na primeira relacao. Servicos de saude: metade dos escolares usaram
      nos ultimos 12 meses. A exposicao de fatores de risco como alcool, sexo inseguro
      e praticas e condicoes violentas e elevada na adolescencia. Torna-se importante a
      adocao de politicas publicas e acoes intersetoriais, plurais e abertas a
      singularidade, voltadas para a protecao da saude de adolescentes e jovens.
      METHODS: theoretical policy analysis based on narrative review of the three
      editions of the PeNSE. The articles identified were categorised by priority
      issues for public policy intervention. RESULTS: cigarette smoking held stable,
      while use of other tobacco products increased by 18%. Regular alcohol use
      declined from 27.3% (2009) to 23.2% (2015). Drug experimentation increased, while
      family supervision produced protective effects against tobacco, alcohol and drug
      use. All indicators of violence increased, including involvement in fights where
      someone used a firearm or melee weapon. Diet and physical activity displayed
      predominantly unhealthy habits: (only 20% exercised for an hour or more daily).
      Sexuality: condom use at first intercourse decreased from 75.9% to 66.2%. Half
      the students had used a health service in the prior 12 months. CONCLUSION:
      exposure to risk factors, including alcohol, unsafe sex and violent behaviour and
      conditions, is high in adolescence, making it important to adopt public policies
      and inter-sectoral actions that are plural and open to singularity in order to
      protect the health of adolescents and youth.

PMID- 30281727
TI  - Elementary and lower secondary school students' perceptions of the Health at
      School Programme: a case study in Belo Horizonte, Brazil.
AB  - The Health at School Programme is a Brazilian inter-sector policy resulting from
      a partnership between the Ministries of Health and Education to expand health
      actions to public school students, with a view to the comprehensive education of
      primary and lower middle school students. This qualitative study was carried out
      in 2016 to investigate Brazilian schoolchildren's perceptions of activities under
      the Health at School Programme. Data were collected from schoolchildren eleven to
      fourteen years of age using the written report (essay) as the instrument.
      Analysis of the reports highlighted two themes: 1. the Health at School Programme
      as care, and 2. the Health at School Programme as benevolence. For some, the
      activities meant the possibility of health care, of identifying problems and
      arranging solutions, and the opportunity for gaining information and learning
      that may be beneficial in maintaining health - the offer was received passively,
      however; for others, they were a blessing, a favour, for which they showed their
      gratitude. The schoolchildren were passive and receptive, without being proactive
      enough to produce their own health. Co-responsibility seems to be a seed that is
      still germinating.

PMID- 30281728
TI  - The prevention of violence in interdisciplinary programs implemented in Brazilian
      and Portuguese schools.
AB  - This paper aims to understand how and to what extent interdisciplinary teams
      supporting public schools in the Brazilian and Portuguese context characterize
      and develop violence prevention actions. The research was carried out from an
      exploratory study through interviews with 24 professionals and later, a thematic
      analysis was done. The results indicate that prevention is always pointed out as
      a possibility in the Portuguese Program; in the Brazilian program, in addition to
      prevention-oriented discourses, limits regarding the realization of preventive
      activities in schools are also mentioned. In the locations investigated, flagged
      prevention actions are shown incipiently when compared to actions advocated by
      the WHO and the Pan American Health Organization. It is argued that a more
      strategic vision of the Ministry of Education and the Education Secretariats
      could contribute to avoid the sole accountability of schools concerning
      prevention of violence and thus enhance the decline of this phenomenon and favor
      its effects in the long term.

PMID- 30281729
TI  - Negative self-perceived health associated with school violence in adolescents.
AB  - OBJECTIVE: To verify the association between negative self-perception of health
      and school violence in adolescent students of the Municipality of Olinda (PE),
      Brazil. METHODS: This is a cross-sectional, analytical and school-based study
      with a sample consisting of 2,614 adolescents selected through a strategy of
      random sampling in conglomerates. The information was obtained through the
      questionnaire "Youth Risk Behavior Survey" from which the issues of violence and
      self-perceived health were retrieved. Data were tabulated by Epi-data version 3.1
      program and transcribed for SPSS version 22. The Chi-square test and the stepwise
      binary logistic regression model were used for data analysis. RESULTS: We
      observed that 26.7% of adolescents had a negative self-perception of health, and
      this was greater among girls. Concerning school violence, negative self
      perception was associated with feelings of sadness, suicidal thoughts, bullying
      at school, robbery at school and safety at school. Gender and age were also
      associated (p < 0.05). CONCLUSION: We reinforce the need for culture and peace
      actions in adolescence, involving the school environment to reflect on poor
      health assessed by adolescents and reduce the rate of violence.

PMID- 30281730
TI  - Challenges of anorexia nervosa in adolescence: ethnography in a public health
      service of Rio de Janeiro, Brazil.
AB  - Through anthropological, ethnographic research, this paper seeks to reflect on
      the dynamics of the daily functioning of a public health service specialized in
      the treatment of eating disorders, as well as on the process of illness
      experienced by adolescents who publicly face anorexia nervosa. The Eating
      Disorders Program observed in Rio de Janeiro provides both outpatient care and
      hospitalization. Fieldwork provided the knowledge about care provided to
      adolescents and their families, as well as the difficulties experienced by the
      multi-professional team. The closer coexistence of the researcher and health
      services facilitated the identification of the many challenges that permeate the
      health professional-user relationship, professional lack of motivation in the
      face of the complex disease, lack of qualification to treat adolescents, and
      other obstacles. We seek to stress the importance of this theme for the Brazilian
      Public Health, with the development of guidelines to orient health services, as
      well as public health policies that promote the establishment of programs,
      actions and activities aimed to give visibility and ensure rights for people with
      eating disorders in the country.

PMID- 30281731
TI  - Young people's power of action in a peripheral community: confrontations and
      challenges.
AB  - This article, based on doctoral research, aims to understand and draw attention
      to forms of social participation by young people living in a peripheral community
      on the coast of Sao Paulo State. It also examines the manners of health
      production encountered by the subjects themselves, to reveal how young people
      have approached this in a context of marked inequality. The young study
      participants were involved in the activities of an NGO and a hip hop group, where
      the researcher was placed. The results were constructed on the basis of
      observations recorded in field diaries and semi-structured interviews, and
      analysed using the Depth Hermeneutics methodology. They indicate that building
      community ties expresses the participation of young people and contributes to
      tackling inequalities and social exclusion. Participation in groups has proven
      potent and able to shape processes of autonomy, self-care and care for others.
      However, they appear as isolated initiatives by other institutions. It is also
      challenging to think of ways of understanding young people's participation,
      participating together with them in their lives in their contexts, making for
      horizontal relationships and surmounting the ideas of homogenisation, control and
      tutelage of this population.

PMID- 30281732
TI  - Experiment and learning in the affective and sexual life of young women from a
      favela in Rio de Janeiro, Brazil, with experience of clandestine abortion.
AB  - This paper discusses the topic of first sexual intercourse in adolescence
      focusing on the course of ten young girls with experience of induced abortion
      living in a favela in Rio de Janeiro. The analysis uses the description of the
      process of entry into sexuality as a strategy to elucidate the context of
      pregnancy and the first clandestine abortion in the affective-sexual path of
      girls interviewed. The first sexual intercourse is a realm of sexuality and
      social life involving socialization, interpretation of rules and meanings, system
      of attitudes, ways of approximation, control and modeling of affections, emotions
      and gender relationships. The results showed that the age difference between
      couples in sexual initiation is significant, clarifying the context in which
      decisions on contraceptive methods, pregnancy and abortion were held. We noted
      that adolescents subject to difficult decisions about their sexuality and
      reproduction at a time of life where they still lack sexual and reproductive
      experience. The data collected show the importance of strengthening of public
      policies, discussions on gender and adolescent sexual and reproductive rights in
      many spheres of society, such as schools, family and other institutions.

PMID- 30281733
TI  - DECIDIX: meeting of the Paulo Freire pedagogy with the serious games in the field
      of health education with adolescents.
AB  - INTRODUCTION: Health education with adolescents is a challenge. Serious games are
      considered strategic tools, and their effectiveness is related to the pedagogical
      model adopted. Health education can promote leadership and autonomy, especially
      since is based on Paulo Freire's Pedagogy as the theoretical foundation.
      OBJECTIVE: To analyze the contributions of the DECIDIX serious game for
      educational purposes, supported by Paulo Freire's foundations, applied to health
      education with adolescents in the sexual and reproductive field. METHODS: Data
      were acquired through the validation of DECIDIX, which was carried out in two
      stages: i) with adolescents, and, ii) with health and education professionals.
      Data were registered through an audio recording of interventions; focus group;
      interviews and (participant and non-participant) observation. Also, data were
      qualitatively coded and categorized. Theoretical approach: Paulo Freire's
      theoretical foundations supported both, DECIDIX development and the analysis of
      its effectiveness. RESULTS: DECIDIX is a tool that assists the educator in
      educational activities using Freire's constructs, aiming the establishment of
      horizontal and dialogical relationships between educators and adolescents, and
      also, promoting experiences to develop critical reflection and autonomy.

PMID- 30281734
TI  - Oral health of quilombola and non-quilombola rural adolescents: a study of
      hygiene habits and associated factors.
AB  - This study evaluated oral hygiene habits and their association with
      sociocultural, environmental factors and factors related to the use of dental
      services among Quilombola and non-Quilombola rural adolescents from inland Bahia.
      Thiswas a cross-sectional study conducted in 2015. Prevalence and prevalence
      ratios were estimated for the outcomes and multiple Poisson regression analysis
      with robust variance was performed. We interviewed 390 adolescents, of which
      42.8% were Quilombola. Poor tooth brushing and non-flossing were found in 33.3%
      and 46.7% of adolescents, respectively. Poor tooth brushing was increased by male
      gender (PR = 1.45), not living with both parents (PR = 1.45), lower hand hygiene
      habit (PR = 1.72) and worse oral health self-assessment (PR = 1.38). Non-flossing
      was associated with economic level E (PR = 1.54), older age (PR = 0.91), lower
      hand hygiene habit (PR = 1.53) and worse oral health self-assessment (PR = 1.33).
      Different associated factors were observed between Quilombola and non-Quilombola.
      It is necessary to consider the specificities of the populations for the
      promotion of adolescent oral health and the importance of the intersectoriality
      between education and health and care to families.

PMID- 30281735
TI  - Heteronomy in adolescent health: an integrative literature review.
AB  - Adolescents' health rights are not restricted to having their demands understood,
      but require their being respected as autonomous subjects and the agents of their
      own care. However, considering adolescents' rights in terms of their autonomy in
      the day-to-day of the health care service, the situation is precarious as a
      result of heteronomy, subjection of the individual to the will of others. A
      search for articles was conducted in the Scopus, PubMed and BVS databases, cross
      referencing with the descriptors: "saude do adolescente" ("adolescent health") ,
      "responsabilidade civil" ("civil responsibility") and "responsabilidade
      parental", ("parental responsibility"). After inclusion and exclusion criteria
      were applied, 32 studies were analysed. The results indicated that adolescents
      are generally not consulted in parents' or guardians' decision making about their
      health care, and also that the family relationship is established under rules
      maintained by punishment, accountability and control, while dialogue is
      neglected. In that light, there is a need for measures to protect and promote
      autonomy, while academic discussion of the relation between adolescent health and
      heteronomy, considering the fields of human rights and health, requires more in
      depth evaluations with a view to providing legal guidance on parent's day-to-day
      role in adolescent health care.

PMID- 30281736
TI  - Activity limitation in elderly people in the European context of gender
      inequality: a multilevel approach.
AB  - The objective of the present study was to examine the magnitude of gender
      differences in activity limitations among the elderly, and the effect of the
      health and social individual factors and the context of social gender inequality
      in Europe. Cross-sectional design was performed. The study population included
      residents aged 60 years or over from 17 countries that participated in the Survey
      of Health, Ageing and Retirement in Europe conducted in 2010-13 (n = 49,685).
      Gender differences in activity limitation in each country was estimated. For
      multilevel analysis adjusted linear mixed effect models were used, where the
      intercept and 'sex' were considered random effects, with the 95% confidence
      intervals. The activity limitation index was created from a two parameter
      logistic combined models of item response theory. The average activity limitation
      index was significantly higher in women, (g10 = b1j = 0.36, p < 0.001), and was
      then controlled by individual and contextual factors, while the extent of these
      differences varied among countries. The European countries with the greatest
      gender differences in activity limitations were those with the greatest social
      gender inequalities, with women presenting a significant disadvantage.

PMID- 30281737
TI  - Family burden among caregivers of people with mental disorders: an analysis of
      health services.
AB  - The objective of this study was to analyze the objective and subjective levels of
      burden felt by family caregivers of patients who were treated at three
      institutions: a General Psychosocial Care Center (known as 'CAPS Geral'), a CAPS
      center for Alcohol and Drugs ('CAPS AD') and the Psychiatric Admissions Unit of a
      General Hospital ('UIPHG') in the municipality of Sobral, Ceara State, Brazil.
      The study included 385 caregivers, 216 of whom were in the CAPS Geral, 86 in the
      CAPS AD and 83 in the UPHG, and applied the Family Burden Interview Scale (FBIS
      BR). Excel and SPSS were used to organize and analyze the data, and a 5%
      significance level was applied. The results show that the general objective
      burden was greater for caregivers at the UIPHG. This group was also found to bear
      a greater objective burden with regard to caring in day-to-day life. The analysis
      of the subjective sub-scales showed that caregivers from the UIPHG group were
      most troubled by supervising problematic behaviors and also by the future and
      patient's type of care and medical treatment. Variables including sex and age
      were associated with burden.

PMID- 30281738
TI  - [Childhood Mental Health Problems in Primary Care].
AB  - The present population study aimed at identifying the prevalence of mental health
      problems (MHP) and describing health services use in a sample of children
      attending Primary Healthcare Units (PHU) in the city of Sao Paulo. Caregivers of
      825 6-11 years old children were assessed. MHP were assessed with the Strength
      and Difficulties Questionnaire and health services use with an adapted version of
      the Client Receipt Inventory Children's version. Prevalence of internalizing and
      externalizing MHP was 30.7% and 18.3%, respectively. Pediatricians were the most
      consulted health professional (56.7%) and psychologists the most consulted mental
      health professional (7.9%). Only 3 children were under medication treatment for
      MHP. The high prevalence of MHP among children in the primary care setting and
      the low rate of treatment constitute a public health problem. Training programs
      for health professionals are relevant to help identify and refer MHP cases.

PMID- 30281739
TI  - [Quality of life of the work of physical therapy course teachers in Goiania in
      the State of Goias, Brazil].
AB  - The scope of this article is to analyze the quality of work life of the physical
      therapy course teachers in the city of Goiania in the state of Goias. It involved
      a cross-sectional study of 65 physical therapy teachers in Goiania. The
      participants who had worked for less than six months in the profession and those
      who failed to fill out the questionnaire in full were excluded from the research.
      A socio-demographic and the Total Quality of Work Life (TQWL-42) questionnaire
      were used to assess the quality of work life. It was established that the
      teachers who taught in graduate courses and who held management positions
      presented significantly better averages than those who only taught in
      undergraduate courses. Satisfaction with income and with the teaching activity
      also showed significant results influencing the quality of work life of the
      participants. Work in positions and locations that allow greater autonomy, status
      and remuneration, as well as subjective evaluation of satisfaction with income
      and teaching work, influenced the quality of work life of physical therapy
      teachers.

PMID- 30281740
TI  - [Factors associated with Sisvan Web coverage for children under 5 years of age,
      in the municipalities of the Regional Health Inspectorate of Belo Horizonte,
      Brazil].
AB  - The objective of this research was to analyze the factors associated with the
      Food and Nutrition Surveillance System (Sisvan Web) coverage for children under
      five years of age in the municipalities of the Regional Health Inspectorate of
      Belo Horizonte (HRS-BH). Sisvan Web coverage data were collected from September
      to October 2012. Simultaneously, a "semi-structured questionnaire about the
      Sisvan operation" was sent to identify the technical references of municipalities
      studied. The coverage was calculated by dividing the number of under five-year
      old children covered by Sisvan by the total number of similarly under five-year
      old children obtained from the 2010 IBGE census. The Median Sisvan Web coverage
      of children in the HRS-BH municipalities was 5.59%, with coverage values ranging
      from 0.55% to 35.8%. Among the variables studied, the only one that revealed
      significant statistical association (p < 0.05) with Sisvan Web coverage was the
      lack of professionals to collect data. The results revealed the need for greater
      awareness of health managers and public health professionals about the importance
      of the nutritional diagnosis situation of the population through Sisvan Web.

PMID- 30281741
TI  - [Recommendation of ICD-10 codes for surveillance of adverse drug reactions and
      drug intoxication].
AB  - ICD-10 is the 10th revision of the International Statistical Classification of
      Diseases and Related Health Problems (ICD), a medical classification list by the
      World Health Organization. It contains codes for diseases, signs and symptoms,
      abnormal findings, complaints, social circumstances, and external causes of
      injury or diseases. Associations between variables were evaluated using Pearson's
      chi-squared test and multiple correspondence analysis. Six hundred and ninety-one
      (691) codes were identified related to adverse drug reactions (52.1%) and drug
      poisoning (47.9%). A total of 687 (99.4%) and 511 (73.9%) codes were validated in
      1st and 2nd validation, respectively. There were statistically significant
      differences (p <0.05) between adverse reactions and drug poisoning in the
      variables used to characterize the reference list. The association between drug
      and hospital admission and death was statistically significant when stratified by
      type of adverse event (p <0.001). Three groupings of codes were identified in
      multiple correspondence analysis where there are associations between categories
      of response assessed. The reference list can be a useful tool in
      pharmacovigilance actions in Brazil.

PMID- 30281742
TI  - Expansion of the object of surveillance for occupational accidents: history and
      challenges underwent by a reference center aiming at prevention.
AB  - The Surveillance System for Occupational Accidents (Sistema de Vigilancia em
      Acidentes de Trabalho - SIVAT) established by Reference Center for Workers'
      Health (Centro de Referencia em Saude do Trabalhador - CEREST-Piracicaba) in 2003
      represents an experience consolidated according to the guidelines formulated by
      the National Network for Integral Care of the Workers' Health (Rede Nacional de
      Atencao Integral a Saude do Trabalhador - RENAST). The present article analyzes
      the history and development of SIVAT at CEREST - Piracicaba from the perspective
      of cultural-historical activity theory. The historical data comprise interviews,
      documents and observations performed by the researchers. Analysis showed that the
      studied activity underwent two cycles of expansion. During the first cycle,
      CEREST actions sought to adequate the targeted companies to the legislation in
      vigor. During the second cycle, actions aimed at introducing changes relative to
      organizational determinants in the targeted companies that CEREST staff
      identified as causes of accidents. A new modality of formative intervention,
      called Change Laboratory (CL), seems to be useful to attain the goal of
      prevention; it involves analysis of the causes of accidents, activity remodeling
      and implantation of solutions by developing agency in the targeted organizations.

PMID- 30281743
TI  - Prevalence and factors associated with surfactant use in Brazilian Neonatal
      Intensive Care Units: A multilevel analysis.
AB  - The treatment with exogenous surfactant reduces mortality and the risk of
      complications in preterm newborns with Respiratory Distress Syndrome. Higher
      usage levels have been associated with individual and institutional factors. The
      study aimed to identify these factors associated with use of this technology in
      16 public Brazilian Neonatal Units using logistic multilevel analysis. In a
      sample of 630 newborns the use at some time was 82.6%. Only 24.7% made use of
      this technology up to two hours after birth. An intraclass correlation of 0.30
      showed that 30% of the variance in the use of exogenous surfactant could be
      assigned to the contextual level. In the final model, a greater severity score
      (SNAPPE-II) was associated with increased surfactant use (OR = 2.64), whereas
      being small for gestational age (SGA) (OR = 0.59) was associated with lower use
      of this technology. At the contextual level the number of beds in the unit >15
      (OR = 5.86), units with higher complexity (OR = 1.73) or units with implemented
      Kangaroo Mother Care (OR = 2.91), especially units in Rio de Janeiro state (OR =
      16.17) were associated with greater surfactant use. Although individual clinical
      features explained most of the variation in the use of this technology, factors
      linked to the institution were also of utmost importance.

PMID- 30281744
TI  - Multimorbidity, depression and quality of life among elderly people assisted in
      the Family Health Strategy in Senador Guiomard, Acre, Brazil.
AB  - This study analyzed the association between multimorbidity, depression and
      quality of life among the elderly in the Family Health Strategy (FHS). A cross
      sectional study was conducted among the elderly in the FHS in Senador Guiomard
      (State of Acre). The study employed the Geriatric Depression Scale (GDS-15) and
      the Quality of Life Questionnaire (WHOQOL-BREF). Differences in descriptive
      variables in elderly people with and without multimorbidity were estimated using
      Pearson's chi-squared test, while the associations between multimorbidity and
      depression and quality of life were estimated using the logistic regression
      technique. It was seen that elderly people with depression represented 27% of the
      sample, this being more prevalent among elderly people with multimorbidity than
      those without, the former being twice as likely to be subject to depression.
      Likewise, individuals with multimorbidity had a greater chance of worse quality
      of life in the physical, social and total quality of life domains (all with p <=
      0.010), though not in the environmental domain (p = 0.493). Thus, multimorbidity
      in the elderly is associated with the presence of depression and poor quality of
      life, which imposes the challenge on the FHS of guaranteeing the elderly living
      out their senescence without suffering and diminished quality of life.

PMID- 30281745
TI  - [Biomedical knowledge and health policies: Hemolytic Uremic Syndrome and
      Fibromyalgia].
AB  - The article deals with the construction of knowledge about diseases. The general
      objective is to analyze the process of constructing scientific knowledge of two
      diseases in comparative perspective: Hemolytic Uremic Syndrome and Fibromyalgia.
      The work reflects on the construction of biomedical knowledge and health
      policies, specifically how scientific knowledge impacts on the design of
      policies. Our research strategy was based on the analysis of scientific
      literature, health programs and bills of Argentina. The analysis was based on the
      axial model of diagnostic categories (semiological, morphological, explanatory
      and epidemiological) developed by Camargo Jr in order to detect how the
      distinctive features of biomedical sphere is translated into the political
      sphere. The investigation showed that the hierarchy given to each axis when a
      disease is defined at the moment of designing health policies is curcial. It also
      revealed that when biomedicine can not define the disease, based on their
      clinical and epidemiological reasoning, the roles are reversed. Then it is
      politics that recognizes the disease and gives the legitimacy that patients need.

PMID- 30281746
TI  - Guidelines for child health: language development on focus.
AB  - Language disorders impact on child overall development. Policy directives for the
      child guide on ways to follow up child development for greater efficiency and
      effectiveness. The aim of this paper was to identify the policies positions of
      the proposals on the attention to language problems in the child health field.
      From a documental research, national and international guidelines were reviewed
      in order to identify actors, objectives, contexts, motivations, arguments,
      justifications and proposals regarding the follow of child development and child
      language. We performed a critical analysis in order to explain these positions
      and place on discussion the arguments that support them. The results point out to
      consensual aspects that place the problems of child development as
      vulnerabilities producers. Language problems cross the boundaries of political,
      scientific and social matters. These issues are challenges to interdisciplinary
      and intersectoral work and guide the need to promote the most effective responses
      of public policy for people requiring language support. The link of this
      discussion with the concepts of life cycle and human development for achieving
      full citizenship requires further deepening.

PMID- 30281747
TI  - [Health and religions: practices and meanings in dialogue and dispute].

PMID- 30281748
TI  - ["We are body, soul and spirit": Person, disease and processes of healing and
      exorcism in contemporary Catholicism in Argentina].
AB  - At the intersection of religion and health, demands for healing, liberation and
      exorcism express undefined discomforts that span from physical and psychiatric
      conditions to relational and psychological problems. To understand this growing
      demand in the population, this study seeks to analyze, on the one hand, the
      underlying conceptions of person and disease and, on the other, the therapeutics
      that priests and their assistants put into action, based on an ethnographic study
      with participant observation and in-depth interviews carried out between 2013 and
      2017 in parishes in the city of La Plata and other localities of the province of
      Buenos Aires. The results enable us to understand that the conception of person
      based upon which therapeutic actions are carried out involves an expansion of the
      individual to the physical, psychological and spiritual planes, and that the
      notions of disease and wellbeing include the person, their environment and past
      generations.

PMID- 30281749
TI  - [Phantoms and inflammations: reflections on the intersections between
      therapeutics and religion in India].
AB  - This article looks at the presence and key role of nonhuman beings endowed with
      intention in the diagnosis and cure of illness. Based on the framework of studies
      of pluralism and itineraries of healing, the article reflects on the persistence
      of the category of the phantom - a nonhuman entity endowed with intentionality -
      in such paths of curation, alongside biomedicine and its diagnostic categories.
      The data upon which this article is based were collected over the course of
      numerous ethnographic field visits carried out between 2005 and 2015 in a network
      of villages located in the Garhwal region of the Uttarkashi district, in the area
      northwest of Uttarkhand, India. Using these data, the article attempts to reflect
      on the reasons why patients, in certain contexts throughout the diagnosis and
      healing process, seek out different specialists, often at the same time.

PMID- 30281750
TI  - [Spirituality and health: problems during pregnancy and postpartum and their
      consequences in women and children's life trajectories (Salta, Argentina)].
AB  - This article addresses the relationship between health and spirituality through
      the analysis of narratives of illnesses that occur during pregnancy and
      postpartum and that affect women and children in rural communities of Molinos
      (Calchaqui Valleys, Salta). It is based on research carried out from 2009-2017,
      in which 33 semi-structured interviews were conducted with women caring for
      children under six years of age. We focused on the way in which the interviewed
      women presented the sequence of events surrounding the emergence of illnesses
      affecting their own health and that of their children, in which organic,
      emotional and spiritual aspects interact in both the etiology of the illness and
      its treatment. We analyze as an example susto [fright] and its variations, as
      well as recaida [relapse] and matriz [womb]. The meanings attributed to these
      illnesses stress the spiritual dimension involved that justifies the use of
      traditional medicine resources. Our approach seeks to go beyond a taxonomic and
      essentialist perspective to focus on aspects involved in the process of the
      experience of illness.

PMID- 30281751
TI  - Mal paraje and mala hora: remarks on the naturalistic violence towards Andean
      medical knowledge.
AB  - The local notions of mal paraje [bad place] and mala hora [bad time] are key to
      explaining many illnesses in Andean medical knowledge. Notwithstanding the
      relevance of these notions ethnographically, neither anthropological research nor
      biomedical knowledge has properly dealt with these local distinctions, and have
      largely relegated them to the shadows. Our aim is to examine the origin of this
      shortcoming of anthropological and biomedical knowledge production. Our
      hypothesis is that such shortcoming is related to the implicit use of certain
      naturalistic theoretical presuppositions, both from the point of view of social
      sciences and from the point of view of biomedical research, producing symbolic
      and epistemic violence against Andean medical knowledge which we call
      naturalistic violence. In methodological terms we examine ethnographic data from
      the Aymara community of Camina (Tarapaca, Chile) and the literature produced on
      this topic. We focus on the notions of mal paraje and mala hora using the content
      analysis technique. We conclude that the main naturalistic obstacles include the
      treatment received by territorial entities, the relationships established among
      these entities and human beings (reciprocity), and the conceptions of space/time
      present in the diagnosis of a disease.

PMID- 30281752
TI  - [Between doctors and healers: managing meanings and practices of the health
      disease-care process in an Argentine Catholic charismatic movement].
AB  - This work describes and analyzes the trajectories and strategies in the search
      for healing among participants of a charismatic Catholic healing movement in
      Argentina. Using ethnographic research carried out between July 2009 and April
      2015, the article focuses on conceptions, practices and experiences surrounding
      health-disease-care processes. It is highlighted that disease management requires
      both a cognitive and a practical response, in this case involving two primary
      therapeutic resources: biomedicine and religious therapies. It is also postulated
      that each resource is sought at specific moments in the trajectories and the
      passage from one to another implies a change from a restricted to a holistic
      notion of the health-disease-care process.

PMID- 30281753
TI  - [Beyond therapy and religion: a relational approach to the spiritual construction
      of wellbeing].
AB  - Taking into account the discontinuity between the body and the soul as a
      manifestation of the dominant "great division" of modernity, this paper intends
      to reflect critically on the scope of this division in the analysis of the
      therapeutic dimension of New Age style spirituality. Through participant
      observation, open-ended interviews and shared experiences with members of a
      spiritual movement of Indian origin, The Art of Living, carried out between 2012
      and 2017 in Buenos Aires, Argentina, we describe two processes. First, the
      institutional discourse of the movement and its location within public disputes
      regarding the tension between the therapeutic and the religious. Second, we
      analyze regimens of everyday relationships that produce multiple agencies and a
      spiritual grammar. We then suggest the importance of attending to a relational
      and assembled framework that challenges the more conventional dualism between the
      therapeutic/religious in the light of a more general contemporary process of
      ordinarization in the management of well-being.

PMID- 30281754
TI  - [The representation of deafness: the body and religion as agents of
      socialization].
AB  - The identification of the body as well as the family and religion in the
      socialization processes of deaf people are examined based in the epistemological
      reflection of the symbolic relational paradigm within the framework of symbolic
      interactionism. A longitudinal study was carried out during the years 2016 and
      2017 following ten life trajectories, chosen from a sample of narratives of deaf
      subjects in the urban area of Bogota (Colombia). Deaf adults who identified with
      contexts that could be described using the concept of alternation, had children
      of any age, were users of sign language and had experienced subjective processes
      related to Deaf culture were selected. In particular, situations of religion and
      health emerge in which the body is resignified in deaf adults, generating the
      questioning of professional interventions and discarding perceptions of exclusion
      in order to confer new meaning to the body as a socializing agent.

PMID- 30281755
TI  - [Meanings of religious work in contexts marked by violence: a study in a complex
      of shantytowns in Rio de Janeiro].
AB  - The purpose of this study is to understand the meanings of religious work in the
      prevention of violence and in the recovery of people involved in illicit acts in
      a complex of shantytowns in Rio de Janeiro, Brazil. The activities of religious
      entities in the territory, the view of religious leaders regarding their role and
      that of their church, and the representations of the territory and of the people
      who commit violent acts were analyzed. Using a qualitative approach, participant
      observation and interviews of religious leaders and "converts" were conducted
      between 2010 and 2012. The resulting narratives were treated using enunciation
      analysis. The leaders emphasize the importance of their churches' actions in
      violent and precarious areas, while the "converts" highlight the role of
      evangelization in their religious conversion. However, the relationships between
      religion and violence are complex, involving various types of trajectories and
      behaviors; in this way, the strength of religious support in the conversion
      process is both highlighted and questioned. The text concludes that churches'
      actions tend to be palliative and focused on the individual and therefore do
      little to transform reality, with the church potentially taking on roles of
      social control and pacification.

PMID- 30281756
TI  - [Multifaith rooms in the Catalan hospital context: negotiations and tensions in
      the management of religious diversity].
AB  - Multifaith rooms are an emerging model for the management and accommodation of
      the religious diversity that proliferates in the health field. This article
      examines the micropolitics of the design of multireligious spaces in hospital
      contexts. Drawing on recent empirical evidence and the "material turn" in the
      study of religion, we focus on the material negotiations that underlie the
      creation of these religious spaces. The article is based on an ethnographic study
      carried out between 2013 and 2016 using the strategy of a multiple case study (in
      three hospitals) in Catalan. Twelve in-depth interviews with religious leaders of
      different faiths and hospital staff and managers, as well as observations in
      multifaith spaces, were carried out. The article shows that multifaith rooms are
      not conciliatory and integrative per se, but rather constitute contexts of
      tension and contention. We conclude that an inherent conflictual dimension is
      part of the nature of this type of spaces and should be recognized and integrated
      into the management of diversity in hospital contexts.

PMID- 30281757
TI  - [Sociogenesis of evangelical devices for the "rehabilitation" of drug users in
      Argentina].
AB  - In order to reconstruct the origin and development of neo-Pentecostal devices for
      the treatment of addictions in the City of Buenos Aires, Argentina, the article
      analytically puts into historical context the "therapeutic spiritualization" of
      addictive behavior undertaken by evangelical agents since the 1970s and explores
      the way in which the State and religious groups converge in the Recover Inclusion
      Program. Based on qualitative methodology and a sociological approach and carried
      out in 2015 and 2016, the study includes fourteen interviews with teachers,
      leaders and former users of the program, twelve interviews with state officials,
      participant observation in training courses and a corpus made up of documents
      related to both institutions. The emergent processes of political and religious
      institutionalization were analyzed according to three dimensions: a) charisma and
      its opposite, bureaucracy, b) the dynamic role of the second lines of leadership
      and c) the networked organization structures. It is concluded that points of
      convergence and analogies exist in the dynamics of evangelical and public
      institutionalization in addiction treatment.

PMID- 30281758
TI  - [Between religion and the State: the case of the Expo Promo Salud events in the
      province of Buenos Aires].
AB  - Religions have historically established ways to regulate the lives of their
      followers, impacting conceptions of wellbeing and health. Likewise, state
      agencies have incorporated a more complex definition of health, including a lack
      of bodily illness, stability, and social, psychological, emotional and spiritual
      wellbeing. Using the category of care in a broad sense, we seek to put these
      conceptualizations into tension in order to identify points of agreement and
      discrepancy among the ways of defining health and wellbeing by state and
      religious agents. Using a qualitative approach, content analysis of documents,
      participant observation and formal and informal interviews with state and
      religious agents were carried out in the framework of two events held in 2016 and
      2017 by the Buenos Aires Provincial Office of Religions under the name Expo Promo
      Salud. These events were generated to make visible the actions carried out by
      religions in the area of health in general and problematic drug use in
      particular. In this way, the article seeks to analyze the ways of discursively
      defining care, health and wellbeing and their possible impact on the design of
      public policies.

PMID- 30281759
TI  - [Practices in search of legitimacy: the contemporary use of ayahuasca, between
      religious and therapeutic vindications].
AB  - In recent decades, the growing interest of Westerners in the psychotropic brew
      ayahuasca and the participation in exotic rituals has led to the multiplication
      of "shamanic centers" in the Peruvian Amazon. Among these, Takiwasi is a
      therapeutic community that welcomes hundreds of national and foreign clients
      every year. This institution, created by a French physician in 1992, was
      originally intended to propose a therapeutic alternative for the treatment of
      addiction, characterized by the use of tools of Peruvian mestizo shamanism,
      biomedicine and clinical psychology. The diachronic evolution of the institution
      is however marked by the growing use of elements of the Catholic tradition. In
      this article, I will examine the hypothesis that these transformations can be
      interpreted as the effects of the globalization of the use of ayahuasca and its
      legal and political consequences. Thus, the case of Takiwasi underlines the role
      played by religious traditions and the medical field in the construction,
      legitimization and maintenance of new and hybrid practices that are multiplying
      around the use of ayahuasca.

PMID- 30281760
TI  - [Processes of institutionalization of non-Catholic chaplaincy and spiritual aide
      in public hospitals of Argentina].
AB  - This article seeks to reconstruct how the process of institutionalization of a
      presbytery of non-Catholic chaplains developed as a way to adapt and interact
      with public institutions in Argentina, particularly health care institutions. For
      this purpose, qualitative interviews with religious actors trained in bioethics
      were carried out, in addition to participant observation in training spaces and
      conferences on health and bioethics and documentary analysis of training material
      and declarations of religious actors on issues of health and bioethics. In a
      context of relations of asymmetry between the State and the churches and the
      pluralization of the religious field, diverse needs for spiritual aide in state
      institutional spaces arise. It is in such a framework that this organization of
      chaplains gains institutional status, developing its own ethos in search of
      recognition, visibility and social legitimacy to offer chaplaincy services in
      institutions where the only chaplains recognized and funded by the State belong
      to the Catholic religion.

PMID- 30281761
TI  - Profile of medical students in the first group of the Faculdade Israelita de
      Ciencias da Saude Albert Einstein.
AB  - OBJECTIVE: To describe first medical students' profile of the Faculdade Israelita
      de Ciencias da Saude Albert Einstein. METHODS: Data were collected using an
      electronic questionnaire during the Biostatistics course in August of 2016. The
      students were inquired about demographic characteristics, data on their secondary
      education and college entrance exams, practice of physical exercise, leisure
      activities done, to have a physician in the family, and specialty that they
      intended to pursue as a career. RESULTS: Most of the students were women aged 18
      to 21 years and who were originally from the state of Sao Paulo, had received
      secondary education in a private school, took a course to prepare for college
      entrance exam, and participated in more than 5 college entrance exams in the same
      year they entered in the School of Medicine. The majority of participants
      practiced physical exercise regularly and were engaged in common leisure
      activities. Most of students (58%) had a physician in the family and more than
      half (52%) did not know which specialty to pursue as career. There was no
      association between relationship with a physician and the student's choice of a
      specialty (p=0.390). CONCLUSION: Although it was the first group of student of
      School of Medicine at Faculdade Israelita de Ciencias da Saude Albert Einstein
      who took a different admission process, our data showed that students' profile is
      similar to students from other colleges.

PMID- 30281762
TI  - What do physicians know about homosexuality? Translation and adaptation of
      Knowledge about Homosexuality Questionnaire.
AB  - OBJECTIVE: To adapt the Knowledge about Homosexuality Questionnaire to Brazilian
      Portuguese, and to assess knowledge of heterosexual physicians on homosexuality.
      METHODS: The following steps for cultural adaptation were made: translation by
      two independent evaluators, translation synthesis, and evaluation of semantic
      properties by the target population, followed by the development of a pilot study
      and administration of the instrument to 224 heterosexual physicians working in
      the Brazilian Federal District. RESULTS: The mean number of correct answers in
      the questionnaire was 11.8 (SD=2.81) out of 18 items, i.e., 65.5%. Catholic and
      evangelical physicians gave a significant lower number of correct answers
      compared with those who believed in other religions or who did not believe in any
      religion (p=0.009), and 40% of sample did not know that homosexuality is not
      considered a disease. CONCLUSION: This study adapted the American instrument
      entitled Knowledge about Homosexuality Questionnaire and provided evidence for
      its validation in Brazil, revealing physicians' lack of knowledge about several
      aspects related to homosexuality. The findings of this study may help in guiding
      improvements in medical training and practice.

PMID- 30281763
TI  - Factors associated with hospital admissions due to hypertension.
AB  - OBJECTIVE: To study the temporality of hospital admissions due to arterial
      hypertension and its associated factors. METHODS: An ecological study with
      secondary data on hospital admissions due to essential arterial hypertension -
      ICD 10, from the Hospital Information System, the Mortality Information System
      and and the Primary Care Information System, between 2010 and 2015. Descriptive
      analysis using means, proportions and linear regression. RESULTS: We recorded
      493,299 hospitalizations due to arterial hypertension from 2010 to 2015, with an
      average annual progressive cost decrease of -7.76% and -24.21%. Of the patients
      admitted, 59.2% were women, 60.2% were non-white and 54.7% were older than 60
      years. The mean length of stay was 4.2 days, and the hospitalization cost was
      R$307.60. The multiple linear regression variables that remained significant were
      the percentage of admissions due to primary care-sensitive conditions, the per
      capita income and the City Human Development Index. CONCLUSION: Hospital
      admissions due to arterial hypertension have an impact on the percentage of
      admissions due to primary care- sensitive conditions. Intensifying primary care
      activities, raising-awareness among professionals to the importance of integrated
      care, and investing in social development are crucial to change the reality of
      hypertension in terms of its control and complications.

PMID- 30281766
TI  - Keep Them From Harm and Injustice?
AB  - Fear remains a major barrier to transparency of hospital errors.

PMID- 30281765
TI  - Percutaneous drainage of iliopsoas abscess: an effective option in cases not
      suitable for surgery.
AB  - The aim of this study were to describe the technique of percutaneous drainage of
      iliopsoas abscess, and to discuss the benefits of using this minimally-invasive
      tool. A single center study with retrospective analysis of patients with psoas
      abscess confirmed by imaging scans, sent to the interventional medicine center
      and submitted to computed tomography and ultrasound-guided percutaneous drainage,
      from November 2013 to August 2016. Seven patients underwent percutaneous drainage
      of psoas abscess in this period. The mean initial drained volume was 61.4+/
      50.7mL (ranging from 10 to 130mL), and the mean drainage duration was 8.3+/-2.8
      days (ranging from 4 to 12 days). The success rate of the percutaneous procedures
      was 71.5%, and two patients required re-intervention. Image-guided percutaneous
      drainage of iliopsoas abscess is a minimally invasive, efficient and safe
      procedure, and an extremely valuable technique, especially for patients who are
      not suitable for surgical repair.

PMID- 30281764
TI  - Cardiac tissue engineering: current state-of-the-art materials, cells and tissue
      formation.
AB  - Cardiovascular diseases are the major cause of death worldwide. The heart has
      limited capacity of regeneration, therefore, transplantation is the only solution
      in some cases despite presenting many disadvantages. Tissue engineering has been
      considered the ideal strategy for regenerative medicine in cardiology. It is an
      interdisciplinary field combining many techniques that aim to maintain,
      regenerate or replace a tissue or organ. The main approach of cardiac tissue
      engineering is to create cardiac grafts, either whole heart substitutes or
      tissues that can be efficiently implanted in the organism, regenerating the
      tissue and giving rise to a fully functional heart, without causing side effects,
      such as immunogenicity. In this review, we systematically present and compare the
      techniques that have drawn the most attention in this field and that generally
      have focused on four important issues: the scaffold material selection, the
      scaffold material production, cellular selection and in vitro cell culture. Many
      studies used several techniques that are herein presented, including biopolymers,
      decellularization and bioreactors, and made significant advances, either seeking
      a graft or an entire bioartificial heart. However, much work remains to better
      understand and improve existing techniques, to develop robust, efficient and
      efficacious methods.

PMID- 30281767
TI  - Advanced Education? TMA Pushes State for Standards in APRN Clinical Training.
AB  - TMA pushes state for standards in APRN clinical training.

PMID- 30281768
TI  - Effects of Opioids and Nonsteroidal Anti-Inflammatory Drugs on Chronic Low Back
      Pain and Related Measures: Results from the PRECISION Pain Research Registry.
AB  - Measuring treatments used by 202 patients with chronic low back pain in the
      PRECISION Pain Research Registry, this study determined the associations of
      opioid and nonsteroidal anti-inflammatory drug (NSAID) therapy with clinical
      status. More than one-fourth of patients did not use nonpharmacologic treatments
      for low back pain. Patients age 50-59 and 60-79 years old were more likely to use
      opioids than younger patients. Patients using opioids reported greater pain and
      back-related disability than did patients using NSAIDs. Patients concurrently
      using opioids and NSAIDs reported greater back-related disability and poorer
      quality of life than did patients using no or other pharmacologic therapy. No
      significant associations between pharmacologic therapy and clinical status
      remained after controlling for potential confounders. Neither opioids nor opioids
      combined with NSAIDs were more effective than just NSAIDs. Greater use of
      nonpharmacologic therapies and better second-line, nonopioid pharmacologic
      therapies appear necessary for more effective treatment of chronic low back pain.

PMID- 30281769
TI  - Talk to Patients About: Flu.
AB  - Flu is serious, and the vaccine can prevent or minimize the illness.

PMID- 30281770
TI  - Stillbirth Still a Problem in Texas: TMA Develops New Recommendations.
AB  - The Texas Medical Association Committee on Reproductive, Women's, and Perinatal
      Health developed new recommendations on stillbirth, which the House of Delegates
      approved in May.

PMID- 30281771
TI  - Getting Ahead of the Flu.
AB  - The 2017-18 flu season was one of the worst in recent years. Can physicians make
      the next one better?

PMID- 30281772
TI  - A Gentle Role Model: Medicine Mourns Death of Revered Cardiologist Mark
      Hausknecht, MD.
AB  - Medicine mourns the death of revered cardiologist Mark Hausknecht, MD.

PMID- 30281773
TI  - Legal Examination: Case Tests Lawsuit Immunity For Medical Examiners.
AB  - Case tests lawsuit immunity for medical examiners.

PMID- 30281774
TI  - Cornered: Proposed Medicare Fee Overhaul Could Box In Doctors.
AB  - Proposed overhaul to Medicare payments for complex patient care visits and same
      day office-based procedures could box in Texas physicians.

PMID- 30281775
TI  - Permanent tooth emergence: Timing and sequence in a sample of Black Southern
      African children.
AB  - OBJECTIVES: This study investigates mean age, sequence, and temporal trends of
      permanent tooth emergence in Black Southern African children and compares the
      findings with other population samples. MATERIALS AND METHODS: This community
      based cross-sectional study involved 639 Black Southern African children between
      5 and 20 years of age. Probit analysis was used to derive the mean age at
      emergence of the permanent teeth. Sex and cross-population comparisons were
      undertaken to determine similarities and differences in emergence timing and
      sequence. RESULTS: Females emerged all teeth earlier except for M3s (p < .05).
      Black Southern Africans have earlier mean ages of emergence compared to
      population samples from the USA, Europe, Australia, and Asia. Sexual dimorphism
      was detected in the mandibular I1/M1 emergence sequence (females, M1 I1 ; males,
      I1 M1 ). The sequence in males is similar in both jaws to males from other sub
      Saharan African, USA, and European samples. Females show a similar sequence
      pattern in the maxilla with other sub-Saharan African, and also Australian and US
      females of European ancestry. There is a high frequency of polymorphism in the
      P1P2C1 emergence sequence, with significantly more P2P1C1 maxillary sequences
      seen among males. Polymorphic variation was common for the I1 M1 sequence in both
      males and females. DISCUSSION: Mean age of tooth emergence among Black Southern
      African children is similar to children from most other sub-Saharan African
      populations. No temporal change was seen in the mean age of emergence. Earlier
      permanent tooth emergence in Black Southern Africans is part of a general sub
      Saharan pattern that is distinct from European and Asian populations.

PMID- 30281776
TI  - Organization of the catecholaminergic systems in two basal actinopterygian
      fishes, Polypterus senegalus and Erpetoichthys calabaricus (Actinopterygii:
      Cladistia).
AB  - Cladistians are a group of basal nonteleost actinopterygian fishes that represent
      an interesting group for the study of primitive brain features, most likely
      present in the ancestral Osteichthyes. We have investigated the catecholaminergic
      (CA) systems in the brain of two representative cladistian species, the bichir
      Polypterus senegalus and the reedfish Erpetoichthys calabaricus, by means of
      antibodies against tyrosine hydroxylase (TH; the first enzyme in the synthesis of
      catecholamines) and dopamine (DA). Double immunohistofluorescence was performed
      for simultaneous detection of TH with nitric oxide synthase, choline
      acetyltransferase, calbindin, calretinin, and serotonin, aiming to accurately
      establish the localization of the CA neurons and to assess possible interactions
      between these neuroactive substances. All forebrain CA groups of cladistians are
      dopaminergic, whereas noradrenergic cells are located within the rhombencephalon.
      Distinct groups of DA immunoreactive (DA-ir) cells were observed in the olfactory
      bulb, subpallium, and preoptic area of the telencephalon. Hypothalamic groups
      were detected in the suprachiasmatic nucleus, retrotuberal and retromamillary
      areas and, in particular, the paraventricular organ showed immunoreactivity to
      dopamine but not to TH. Diencephalic DA-ir groups were detected in the
      prethalamus, posterior tubercle, and pretectum. A small DA-ir cell population was
      observed in the midbrain tegmentum only in Polypterus. CA cell groups were also
      located in the locus coeruleus, solitary tract nucleus, and area postrema within
      the rhombencephalon, the spinal cord, and the retina. The comparison of these
      results with other vertebrates, using a neuromeric analysis, shows highly
      conserved traits in all vertebrates studied but also evidences particular
      characteristics of actinopterygian fishes.

PMID- 30281777
TI  - Feasibility of Implementing Patient Priorities Care for Older Adults with
      Multiple Chronic Conditions.
AB  - Older adults with multiple chronic conditions (MCCs) receive care that is
      fragmented and burdensome, lacks evidence, and most importantly is not focused on
      what matters most to them. An implementation feasibility study of Patient
      Priorities Care (PPC), a new approach to care that is based on health outcome
      goals and healthcare preferences, was conducted. This study took place at 1
      primary care and 1 cardiology practice in Connecticut and involved 9 primary care
      providers (PCPs), 5 cardiologists, and 119 older adults with MCCs. PPC was
      implemented using methods based on a practice change framework and continuous
      plan-do-study-act (PDSA) cycles. Core elements included leadership support,
      clinical champions, priorities facilitators, training, electronic health record
      (EHR) support, workflow development and continuous modification, and
      collaborative learning. PPC processes for clinic workflow and decision-making
      were developed, and clinicians were trained. After 10 months, 119 older adults
      enrolled and had priorities identified; 92 (77%) returned to their PCP after
      priorities identification. In 56 (46%) of these visits, clinicians documented
      patient priorities discussions. Workflow challenges identified and solved
      included patient enrollment lags, EHR documentation of priorities discussions,
      and interprofessional communication. Time for clinicians to provide PPC remains a
      challenge, as does decision-making, including clinicians' perceptions that they
      are already doing so; clinicians' concerns about guidelines, metrics, and
      unrealistic priorities; and differences between PCPs and patients and between
      PCPs and cardiologists about treatment decisions. PDSA cycles and continuing
      collaborative learning with national experts and peers are taking place to
      address workflow and clinical decision-making challenges. Translating disease
      based to priorities-aligned decision-making appears challenging but feasible to
      implement in a clinical setting.

PMID- 30281778
TI  - Multicenter randomized controlled trial assessing the impact of a cervical
      traction maneuver (Amr's maneuver) on the incidence of postpartum hemorrhage.
AB  - OBJECTIVE: To assess the impact of a cervical traction maneuver (Amr's maneuver)
      used in conjunction with active management of the third stage of labor (AMTSL) on
      the incidence of postpartum hemorrhage (PPH). METHOD: The present multicenter
      randomized controlled trial was conducted in Cairo between March 1, 2016, and
      June 30, 2017. Women aged at least 18 years who had singleton pregnancies and
      were candidates for vaginal delivery were enrolled. After block randomization,
      AMTSL was performed for all participants. Following placental delivery, Amr's
      maneuver using cervical traction for 90 seconds was carried out in the study
      group. The primary outcome, incidence of PPH (>500 mL blood loss) within 6 hours
      of delivery, was compared between the study and control groups in an intention-to
      treat analysis. RESULTS: There were 852 patients randomized to the study (n=426)
      and control (n=426) groups. The incidence of PPH was significantly lower in the
      study group compared with the control group (6 [1.4%] vs 19 [4.5%]; P=0.015).
      Absolute risk reduction of 3.1% (95% CI 0.8-5.6), relative risk reduction of 0.32
      (95% CI 0.13-0.78), and number needed to treat of 33 (95% CI 129-18) were
      observed in the study group. CONCLUSION: Amr's maneuver was effective in
      decreasing the incidence of PPH. ClinicalTrials.gov Identifier: NCT02660567.

PMID- 30281779
TI  - Long-term clinical safety of clindamycin and rifampicin combination for the
      treatment of hidradenitis suppurativa. A Critically Appraised Topic.
AB  - CLINICAL QUESTION/SCENARIO: Can therapy with clindamycin and rifampicin be safely
      continued long term beyond the recommended 10-week course? BACKGROUND:
      Clindamycin and rifampicin are used in combination to treat hidradenitis
      suppurativa (HS). There is no data on the efficacy and safety of
      clindamycin/rifampicin combination therapy for HS beyond 10 weeks. METHODS: We
      identified the following major concerns that still lack a proper evidenced-based
      analysis: for rifampicin, drug-induced liver injury, interstitial nephritis, drug
      interaction and hepatic p450 3A4 enzyme induction; for clindamycin, the concern
      was community-acquired Clostridium difficile infection (CA-CDI); and experience
      with long-term treatment. Data sources were used as appropriate to answer the
      question. Systematic searches were used to assess the risk of CA-CDI and
      experience with long-term treatment with clindamycin. RESULTS/IDENTIFIED
      EVIDENCE: The risk for rifampicin-induced liver injury is highest in the first 6
      weeks of treatment, whereas interstitial nephritis is primarily observed during
      intermittent treatment. Enzyme induction due to rifampicin is usually complete
      after about 2 weeks of treatment and reduces clindamycin blood levels by about
      90%. Three meta-analyses identified antibiotic use as a risk factor for CA-CDI.
      Two of them assigned the highest risk to clindamycin. None of them stratified by
      length of treatment. There is extensive experience with rifampicin, primarily for
      the treatment of tuberculosis. Long-term experience with clindamycin is limited.
      DISCUSSION AND RECOMMENDATION FOR CLINICAL CARE: The analysed risks associated
      with a combination of clindamycin and rifampicin for hidradenitis suppurative
      cluster within the first 10 weeks. Treatment can be continued beyond 10 weeks, if
      clinically necessary.

PMID- 30281780
TI  - Imatinib inhibits CSF1R that stimulates proliferation of rheumatoid arthritis
      fibroblast-like synoviocytes.
AB  - In this study, we aimed to explore the effects of imatinib on the proliferation
      of rheumatoid arthritis synovial cell (RA-FLS) and inflammatory responses by
      regulating CSF1R. Differential genes were screened via microarray analysis,
      followed by being analysed through the weighted co-expression network (WGCNA)
      network, that included module and cluster analysis. The relationship between
      imatinib and genes was visualized using the Search Tool for the Retrieval of
      Interacting Genes (STITCH) database. Expressions of mRNA and protein were
      determined by reverse transcription-polymerase chain reaction (RT-PCR) and
      Western blot, respectively. Cell viability was examined via clone formation
      assay, while cell cycle and apoptosis were analysed through flow cytometry
      analysis. The hub gene CSF1R was ultimately determined by microarray analysis and
      WGCNA analysis. Colony-stimulating-factor receptor-1 (SF1R) was highly expressed
      in rheumatoid arthritis tissues and cells, and CSF1R over-expression could
      promote inflammatory responses. Moreover, CSF1R could promote RA-FLS
      proliferation, inhibit apoptosis and accelerate the cell cycle. The targeting
      relationship between imatinib and CSF1R was also validated in this study.
      Imatinib attenuated RA-FLS inflammation in a concentration-dependent manner.
      Meanwhile, imatinib could inhibit RA-FLS proliferation and promote apoptosis,
      ultimately reducing the damage of RA-FLS. Over-expression of CSF1R accelerated
      the cell cycle and proliferation of RA-FLS, while inhibiting cell apoptosis.
      Conversely, imatinib could significantly restrain the cell cycle and viability of
      RA-FLS and accelerated apoptosis via suppression of CSF1R expression. Further,
      histological and serological assay investigated and proved the proinflammatory
      effects of CSF1R in RA rabbits.

PMID- 30281781
TI  - Atrial Fibrillation: Possible Influences of Rate and Rhythm Control Strategy on
      Cognitive Performance.
AB  - OBJECTIVES: To determine whether rate or rhythm control strategy may affect
      cognition in older adults with atrial fibrillation (AF). DESIGN: Retrospective
      analysis of the REgistro POliterapie SIMI database. SETTING: Italian internal
      medicine and geriatric wards. PARTICIPANTS: Individuals aged 65 and older
      (N=1,082, mean age 80.6 +/- 7; 50% male) with AF before hospital admission (for
      any cause). MEASUREMENTS: Evaluation of cognitive performance using the Short
      Blessed Test (SBT) according to rhythm and rate control strategy, anticoagulant
      and antiplatelet therapy, age, education, and comorbidities. RESULTS: Two hundred
      seventy-two participants (25%) received rhythm control therapy, 331 (30.6%) rate
      control therapy, and 479 (44.3%) no therapy of interest. Four hundred thirty-six
      (40.3%) in the total sample and in the different rhythm and rate control strategy
      groups were treated with an oral anticoagulant. Cognitive performance (mean SBT
      score) was found to be higher in the rhythm control group (7.5 +/- 6.6) than in
      the no therapy (9.9 +/- 7.9) and rate control (10.6 +/- 8.3) (p<.001) groups.
      Logistic regression models adjusted for age, sex, education, anticoagulant and
      antiplatelet therapy, and comorbidities found that the rhythm control strategy
      (adjusted odds ratio (aOR)=0.56, 95% confidence interval (CI)=0.40-0.79, p=.001)
      and education (aOR 0.50, 95% CI=0.35-0.62; p<.001) were associated with less
      likelihood of cognitive impairment CONCLUSION: In the absence of anticoagulation,
      rhythm control of AF may protect against cognitive decline. J Am Geriatr Soc
      66:2178-2182, 2018.

PMID- 30281782
TI  - Comment on "Recognition and Diagnosis of Obstructive Sleep Apnea in Older
      Americans".

PMID- 30281783
TI  - Effect of Site-Neutral Payment Policy on Long-Term Acute Care Hospital Use.
AB  - OBJECTIVE: To assess the projected effect of the Centers for Medicare and
      Medicaid Services new site-neutral payment policy, which aims to decrease
      unnecessary long-term acute care hospital (LTACH) admissions by reducing
      reimbursements for less-ill individuals by 2020. DESIGN: Observational. SETTING:
      National 5% Medicare data (2011-12). MEASUREMENTS: We examined the proportion of
      site-neutral LTACH admissions. Regional LTACH market supply was defined as LTACH
      beds per 100,000 residents, categorized according to tertile. We conducted a
      hospital-level analysis to compare the projected effect of site-neutral payment
      on "propensity score" matched high- and low-LTACH-use hospitals. RESULTS: Forty
      one percent of LTACH admissions would be subjected to site-neutral payment. The
      proportion of site-neutral admissions was large, varied considerably according to
      LTACH (median 40%, interquartile range 22-60%), and was only modestly greater
      with greater market supply (Pearson correlation coefficient=0.23, p<.001;
      coefficient of determination=0.10). The site-neutral payment policy would affect
      47% of admissions from the highest-supply regions, versus 30% from the lowest
      supply regions (p<.001); and 43% from high-use hospitals versus 36% from
      propensity score-matched low-use hospitals (p<.001). CONCLUSION: A considerable
      proportion of LTACH admissions will be subjected to lower site-neutral payments.
      Although the policy will disproportionately affect high-use regions and
      hospitals, it will also affect nearly one-third of the current LTACH population
      from low-use hospitals and regions. As such, the site-neutral payment policy may
      limit LTACH access in existing LTAC-scarce markets, with potential adverse
      implications for recovery of hospitalized older adults. J Am Geriatr Soc 66:2104
      2111, 2018.

PMID- 30281784
TI  - Deadenylation by the CCR4-NOT complex contributes to the turnover of hairy
      related mRNAs in the zebrafish segmentation clock.
AB  - In the zebrafish segmentation clock, hairy/enhancer of split-related genes her1,
      her7, and hes6 encodes components of core oscillators. Since the expression of
      cyclic genes proceeds rapidly in the presomitic mesoderm (PSM), these hairy
      related mRNAs are subject to strict post-transcriptional regulation. In this
      study, we demonstrate that inhibition of the CCR4-NOT deadenylase complex
      lengthens poly(A) tails of hairy-related mRNAs and increases the amount of these
      mRNAs, which is accompanied by defective somite segmentation. In transgenic
      embryos, we show that EGFP mRNAs with 3'UTRs of hairy-related genes exhibit
      turnover similar to endogenous mRNAs. Our results suggest that turnover rates of
      her1, her7, and hes6 mRNAs are differently regulated by the CCR4-NOT deadenylase
      complex possibly through their 3'UTRs in the zebrafish PSM.

PMID- 30281785
TI  - Disturbed processing of the carbohydrate-binding module of family 54
      significantly impairs its binding to polysaccharides.
AB  - Carbohydrate-binding modules of the family 54 (CBM54) are characterized by
      spontaneous rupture of the peptide bond Asn266-Ser267 (numbering corresponds to
      that of laminarinase Lic16A of Ruminiclostridium thermocellum). As a result of
      processing, two parts are formed noncovalently connected to each other. Here, to
      gain insights into the functional significance of the internal cleavage, we made
      modifications of the family-conserved processing site in CBM54 of Lic16A. We
      demonstrate that the introduced mutations of residues G264 or S267 to alanine
      block the hydrolysis. Unprocessed, modified proteins bind insoluble
      polysaccharides pustulan, chitin, xylan, Avicel, phosphoric acid-swollen
      cellulose, and beta-d-glucan of the yeast cell wall 2-20 times worse than the
      wild-type module. The data obtained are the first to demonstrate that processing
      is important for the functioning of CBM54s.

PMID- 30281786
TI  - Can plants evolve to meet a changing climate? The potential of field experimental
      evolution studies.

PMID- 30281787
TI  - Sedation for screening MRI in patients with congenital melanocytic naevi under
      the age of one is a successful, safe and economical first-line approach.

PMID- 30281788
TI  - Dental markers of poverty: Biocultural deliberations on oral health of the poor
      in mid-nineteenth-century Ireland.
AB  - OBJECTIVES: Despite subsisting on a low-cariogenic diet comprising virtually
      nothing more than potatoes and dairy products, poor oral health affected the
      quality of life for the poor of nineteenth-century Ireland. This study
      investigates potential biocultural reasons that may explain why this was the
      case. MATERIAL AND METHODS: A total of 6,860 teeth and 9,889 alveoli from 363
      permanent dentitions from the skeletal remains of impoverished adult Irish males
      and females who died between 1847 and 1851 in the Kilkenny Union Workhouse were
      examined for evidence of dental caries, periodontal disease and ante-mortem tooth
      loss. Caries rates were quantified and assessed by crude prevalence, frequencies,
      corrected caries rates and a t-health index, and evaluated by sex and age groups.
      RESULTS: A higher rate of caries was present among 18-25-year-old males than
      females, while the opposite relationship was evident for older age groups. The
      prevalence rates of periodontal disease and ante-mortem tooth loss increased with
      age. When assessed by corrected caries rates, tooth decay is observed at a lower
      rate compared to contemporaneous lower to upper-class population samples from
      London. DISCUSSION: Despite being low cariogenic foods, the potato starch and
      milk lactose of a nineteenth-century Irish laborer's diet would have lowered oral
      pH-values thereby increasing the risk of bacterial fermentation in dental plaque
      resulting in caries. Nutritional features alone cannot explain the high rates of
      dental caries observed in the Kilkenny workhouse population sample, however, and
      lifestyle factors, particularly habitual clay-pipe smoking, is considered a
      significant cause of poor oral health.

PMID- 30281789
TI  - Implementing "Patient-Centered Care": A Revolutionary Change in Health Care
      Delivery.

PMID- 30281790
TI  - Analytical performance of a low-cost multiplex polymerase chain reaction human
      papillomavirus genotyping assay for use in Sub-Saharan Africa.
AB  - We have tested a multiplex polymerase chain reaction (PCR) human papillomavirus
      (HPV) genotyping assay to fill the need for rapid and low-cost HPV detection in
      Sub-Saharan Africa. This method allows high throughput genotyping and
      simultaneous detection of 14 high-risk and two low-risk HPV types, by PCR
      amplification of HPV DNAs in a single reaction tube. In this study, we describe
      stepwise experiments to validate the multiplex HPV PCR assay for determination of
      HPV genotypes from 104 cervical brush samples from Tanzanian women. Assay
      performance was evaluated by determination of intra-laboratory reproducibility,
      sensitivity, and specificity. Further performance was assessed by comparison with
      the widely accepted and validated HPV My09/My11 amplification and hybridization
      assay. Statistics; the Cohen kappa (kappa) and McNemar P values were used to
      analyze interobserver and intermethod agreement. Overall concordance between the
      multiplex and line blot hybridization assays was 99% (per sample) with a kappa
      value equal to 0.95; and 96.49% (per detection event) with a kappa value of 0.92.
      Interobserver reproducibility of the assay per sample was 95.76% with kappa of
      0.91. These results demonstrate that the multiplex HPV PCR assay has high
      analytical sensitivity and specificity in detecting as many as 16 different HPV
      genotypes and that its simplicity and low cost makes it well suited for sub
      Saharan Africa.

PMID- 30281792
TI  - Soil fertility in boreal forest relates to root-driven nitrogen retention and
      carbon sequestration in the mor layer.
AB  - Boreal forest soils retain significant amounts of carbon (C) and nitrogen (N) in
      purely organic layers, but the regulation of organic matter turnover and the
      relative importance of leaf litter and root-derived inputs are not well
      understood. We combined bomb 14 C dating of organic matter with stable isotope
      profiling for Bayesian parameterization of an organic matter sequestration model.
      C and N dynamics were assessed across annual depth layers (cohorts), together
      representing 256 yr of organic matter accumulation. Results were related to
      ecosystem fertility (soil inorganic N, pH and litter C : N). Root-derived C was
      estimated to decompose two to 10 times more slowly than leaf litter, but more
      rapidly in fertile plots. The amounts of C and N per cohort declined during the
      initial 20 yr of decomposition, but, in older material, the amount of N per
      cohort increased, indicating N retention driven by root-derived C. The dynamics
      of root-derived inputs were more important than leaf litter dynamics in
      regulating the variation in organic matter accumulation along a forest fertility
      gradient. N retention in the rooting zone combined with impeded mining for N in
      less fertile ecosystems provides evidence for a positive feedback between
      ecosystem fertility and organic matter turnover.

PMID- 30281793
TI  - Role of the tightly bound quinone for the oxygen reaction of cytochrome bo3
      oxidase from Escherichia coli.
AB  - The coupling of the reaction of a tightly bound ubiquinone with the reduction of
      O2 in cytochrome bo3 of Escherichia coli was investigated. In the absence of the
      quinone, a strongly diminished rate of electrocatalytic reduction of oxygen is
      detected, which can be restored by adding quinones. The correlation of previous
      EPR data with the electrocatalytic study on mutations in the binding site at
      positions, Q101, D75, F93, H98, I102 and R71 reveal that the stabilization of the
      radical is not necessary for the oxygen reaction. The Q101 and F93 variants
      exhibit both well-defined catalytic i-V curves, whereas D75H, H98F, I102W and
      R71H exhibit broad i-V curves with large hysteresis pointing toward a strong
      alteration in their catalytic activity.

PMID- 30281794
TI  - Development of a Clinically Feasible Process for Identifying Individual Health
      Priorities.
AB  - OBJECTIVES: To develop a values-based, clinically feasible process to help older
      adults identify health priorities that can guide clinical decision-making.
      DESIGN: Prospective development and feasibility study. SETTING: Primary care
      practice in Connecticut. PARTICIPANTS: Older adults with 3 or more conditions or
      taking 10 or more medications (N=64). INTERVENTION: The development team of
      patients, caregivers, and clinicians used a user-centered design framework-ideate
      -> prototype -> test ->redesign-to develop and refine the value-based patient
      priorities care process and medical record template with trained clinician
      facilitators. MEASUREMENTS: We used descriptive statistics of quantitative
      measures (percentage accepted invitation and completed template, duration of
      process) and qualitative analysis of barriers and enablers (challenges and
      solutions identified, facilitator perceptions). RESULTS: We developed and refined
      a process for identifying patient health priorities that was typically completed
      in 35 to 45 minutes over 2 sessions; 64 patients completed the process.
      Qualitative analyses were used to elucidate the characteristics and training
      needed for the patient priorities facilitators, as well as perceived benefits and
      challenges of the process. Refinements based on our experience and feedback
      include streamlining the process for greater feasibility, balancing fidelity to
      the process while customizing to individuals, encouraging patients to share their
      priorities with their clinicians, and simplifying the template transmitted to
      clinicians. CONCLUSION: Trained facilitators conducted this process in a busy
      primary care practice, suggesting that patient priorities identification is
      feasible and acceptable, although testing in additional settings is necessary. We
      hope to show that clinicians can align care with patients' health priorities.

PMID- 30281795
TI  - Visual response properties of neurons in the superficial layers of the superior
      colliculus of awake mouse.
AB  - KEY POINTS: In rodents, including mice, the superior colliculus is the major
      target of the retina, but its visual response is not well characterized. In the
      present study, extracellular recordings from single nerve cells in the
      superficial layers of the superior colliculus were made in awake, head-restrained
      mice, and their responses to visual stimuli were measured. It was found that
      these neurons show brisk, highly sensitive and short latency visual responses, a
      preference for black over white stimuli, and diverse responses to moving
      patterns. At least five broad classes can be defined by variation in functional
      properties among units. The results of the present study demonstrate that eye
      movements have a measurable impact on visual responses in awake animals and show
      how they may be mitigated in analyses. ABSTRACT: The mouse is an increasingly
      important animal model of visual function in health and disease. In mice, most
      retinal signals are routed through the superficial layers of the midbrain
      superior colliculus, and it is well established that much of the visual behaviour
      of mice relies on activity in the superior colliculus. The functional
      organization of visual signals in the mouse superior colliculus is, however, not
      well established in awake animals. We therefore made extracellular recordings
      from the superficial layers of the superior colliculus in awake mice, while the
      animals were viewing visual stimuli including flashed spots and drifting
      gratings. We find that neurons in the superficial layers of the superior
      colliculus of awake mouse generally show short latency, brisk responses.
      Receptive fields are usually 'ON-OFF' with a preference for black stimuli, and
      are weakly non-linear in response to gratings and other forms of luminance
      modulation. Population responses to drifting gratings are highly contrast
      sensitive, with a robust response to spatial frequencies above 0.3 cycles degree
      1 and temporal frequencies above 15 Hz. The receptive fields are also often speed
      tuned or direction-selective. Analysis of the response across multiple stimulus
      dimensions reveals at least five functionally distinct groups of units. We also
      find that eye movements affect measurements of receptive field properties in
      awake animals, and show how these may be mitigated in analyses. Qualitatively
      similar responses were obtained in urethane-anaesthetized animals, although
      receptive fields in awake animals had higher contrast sensitivity, shorter visual
      latency and a stronger response to high temporal frequencies.

PMID- 30281797
TI  - The central amygdala to periaqueductal gray pathway comprises intrinsically
      distinct neurons differentially affected in a model of inflammatory pain.
AB  - KEY POINTS: The central nucleus of the amygdala (CeA) encompasses the main output
      pathways of the amygdala, a temporal lobe structure essential in affective and
      cognitive dimensions of pain. A major population of neurons in the CeA send
      projections to the periaqueductal gray (PAG), a key midbrain structure that
      mediates coping strategies in response to threat or stress. CeA-PAG neurons are
      topographically organized based on their targeted subregion within the PAG. PAG
      projecting neurons in the central medial (CeM) and central lateral (CeL) regions
      of CeA are intrinsically distinct. CeL-PAG neurons are a homogeneous population
      of intrinsically distinct neurons while CeM-PAG neurons are intrinsically
      heterogeneous. Membrane properties of distinct CeM-PAG subtypes are altered in
      the complete Freund's adjuvant model of inflammatory pain. ABSTRACT: A major
      population of neurons in the central nucleus of amygdala (CeA) send projections
      to the periaqueductal gray (PAG), a key midbrain structure that mediates coping
      strategies in response to threat or stress. While the CeA-PAG pathway has proved
      to be a component of descending anti-nociceptive circuitry, the functional
      organization of CeA-PAG neurons remains unclear. We identified CeA-PAG neurons in
      C57BL/6 mice of both sexes using intracranial injection of a fluorescent
      retrograde tracer into the PAG. In acute brain slices, we investigated the
      topographical and intrinsic characteristics of retrogradely labelled CeA-PAG
      neurons using epifluorescence and whole-cell electrophysiology. We also measured
      changes to CeA-PAG neurons in the complete Freund's adjuvant (CFA) model of
      inflammatory pain. Neurons in the central lateral (CeL) and central medial (CeM)
      amygdala project primarily to different regions of the PAG. CeL-PAG neurons
      consist of a relatively homogeneous population of intrinsically distinct neurons
      while CeM-PAG neurons are intrinsically heterogeneous. Membrane properties of
      distinct CeM-PAG subtypes are altered 1 day after induction of the CFA
      inflammatory pain model. Collectively, our results provide insight into pain
      induced changes to a specific population of CeA neurons that probably play a key
      role in the integration of noxious input with endogenous analgesia and
      behavioural coping response.

PMID- 30281796
TI  - Self-Reported Physical Function As a Predictor of Hospitalization in the
      Lifestyle Interventions and Independence for Elders Study.
AB  - OBJECTIVES: To explore whether baseline scores on the Mobility Assessment Tool
      short form (MAT-sf), a brief, animated, computer-based means of assessing
      mobility that predicts mobility disability, are associated with number of
      hospitalizations and time to first hospitalization over a median follow-up of 2.7
      years. DESIGN: Post hoc analysis of prospectively gathered data from the
      Lifestyle Interventions and Independence for Elders (LIFE) Study, a randomized
      clinical trial of lifestyle interventions to preserve mobility in older adults.
      SETTING: Eight U.S. academic medical centers. PARTICIPANTS: Of 1,635 sedentary
      community-dwelling older adults enrolled in LIFE, 1,574 completed baseline
      physical function screening including the MAT-sf, with baseline scores ranging
      from 30.2 (low function) to 69.8 (high function) on a scale from 30 to 80.
      MEASUREMENTS: Number of hospitalizations and time to first hospitalization,
      adjusted for age, sex, race, living alone, clinical site, baseline comorbidities,
      number of prescription medications, and cognition. RESULTS: Of the 1,557
      participants with data regarding hospitalization status, 726 (47%) had at least 1
      hospitalization; 78% of these had 1 or 2 hospitalizations. For every 10-point
      lower MAT-sf score, the rate of all hospitalizations was 19% higher in those with
      lower scores (adjusted rate ratio=1.20, 95% confidence interval (CI)=1.08-1.32,
      p<.001). Lower baseline MAT-sf scores were also associated with greater risk of
      first hospitalization (adjusted hazard ratio=1.20, 95% CI=1.09-1.32, p<.01, per
      10-point lower MAT-sf score). CONCLUSION: Low MAT-sf scores identify older adults
      at risk of hospitalization; further study is needed to test interventions to
      reduce hospitalizations in these individuals.

PMID- 30281799
TI  - Cold sensitivity of mitochondrial ATP synthase restricts oxidative
      phosphorylation in Arabidopsis thaliana.
AB  - The combined action of the electron transport chain (ETC) and ATP synthase is
      essential in determining energy efficiency in plants, and so is important for
      cellular biosynthesis, growth and development. Owing to the sessile nature of
      plants, mitochondria must operate over a wide temperature range in the
      environment, necessitating a broad temperature tolerance of their biochemical
      reactions. We investigated the temperature response of mitochondrial respiratory
      processes in isolated mitochondria and intact plants of Arabidopsis thaliana and
      considered the effect of instantaneous responses to temperature and acclimation
      responses to low temperatures. We show that at 4 degrees C the plant
      mitochondrial ATP synthase is differentially inhibited compared with other
      elements of the respiratory pathway, leading to decreased ADP : oxygen ratios and
      a limitation to the rate of ATP synthesis. This effect persists in vivo and
      cannot be overcome by cold-temperature acclimation of plants. This mechanism adds
      a new element to the respiratory acclimation model and provides a direct means of
      temperature perception by plant mitochondria. This also provides an alternative
      explanation for non-phosphorylating ETC bypass mechanisms, like the alternative
      oxidase to maintain respiratory rates, albeit at lower ATP synthesis efficiency,
      in response to the sensitivity of ATP synthase to the prevailing temperature.

PMID- 30281798
TI  - Of puzzles and pavements: a quantitative exploration of leaf epidermal cell
      shape.
AB  - Epidermal cells of leaves are diverse: tabular pavement cells, trichomes, and
      stomatal complexes. Pavement cells from the monocot Zea mays (maize) and the
      eudicot Arabidopsis thaliana (Arabidopsis) have highly undulate anticlinal walls.
      The molecular basis for generating these undulating margins has been extensively
      investigated in these species. This has led to two assumptions: first, that
      particular plant lineages are characterized by particular pavement cell shapes;
      and second, that undulatory cell shapes are common enough to be model shapes. To
      test these assumptions, we quantified pavement cell shape in epidermides from the
      leaves of 278 vascular plant taxa. We found that monocot pavement cells tended to
      have weakly undulating margins, fern cells had strongly undulating margins, and
      eudicot cells showed no particular undulation degree. Cells with highly
      undulating margins, like those of Arabidopsis and maize, were in the minority. We
      also found a trend towards more undulating cell margins on abaxial leaf surfaces;
      and that highly elongated leaves in ferns, monocots and gymnosperms tended to
      have highly elongated cells. Our results reveal the diversity of pavement cell
      shapes, and lays the quantitative groundwork for testing hypotheses about
      pavement cell form and function within a phylogenetic context.

PMID- 30281800
TI  - Photobiomodulation Affects Key Cellular Pathways of all Life-Forms:
      Considerations on Old and New Laser Light Targets and the Calcium Issue.
AB  - After 50 years of studies on photobiomodulation (PBM), there is still so much to
      investigate to understand the laser light-nonplant cells interactions. The
      current scientific knowledge allows to say that the phenomena induced by PBM are
      based on cellular pathways that are the key points of cell life. The mitochondria
      chromophores, also present on the bacterial membrane, the calcium channels, ion
      that regulates the life-and-death cellular processes, as well as the TRP family,
      whose genes have been found in protozoa and suggest that its basic mechanism
      evolved long before the appearance of animals, seem to be elective targets in
      photobiomodulatory events by wavelengths from 600 up to 980 nm. The ambiguous
      resulting cellular communication way, mediated by ATP, ROS and/or calcium, leads
      to cell manipulation, which modifies its metabolism and whose response connects
      all life-forms from bacteria to vertebrates. Because of the Giano-Bifronte
      features of ROS and calcium, as well as the fine balance of energetic
      mitochondrial processes, whose alteration is responsible for several diseases,
      the PBM can show unpredictable results and it requires scrupulous approach to
      avoid cellular damages. However, when carefully applied, PBM is able to improve
      nonhealthy cell's responses and represents a reliable support in human and
      veterinary medicine.

PMID- 30281801
TI  - Functional trait divergence and trait plasticity confer polyploid advantage in
      heterogeneous environments.
AB  - Polyploidy, or whole-genome duplication often with hybridization, is common in
      eukaryotes and is thought to drive ecological and evolutionary success,
      especially in plants. The mechanisms of polyploid success in ecologically
      relevant contexts, however, remain largely unknown. We conducted an extensive
      test of functional trait divergence and plasticity in conferring polyploid
      fitness advantage in heterogeneous environments, by growing clonal replicates of
      a worldwide genotype collection of six allopolyploid and five diploid wild
      strawberry (Fragaria) taxa in three climatically different common gardens. Among
      leaf functional traits, we detected divergence in trait means but not
      plasticities between polyploids and diploids, suggesting that increased genomic
      redundancy in polyploids does not necessarily translate into greater trait
      plasticity in response to environmental change. Across the heterogeneous garden
      environments, however, polyploids exhibited fitness advantage, which was
      conferred by both trait means and adaptive trait plasticities, supporting a 'jack
      and-master' hypothesis for polyploids. Our findings elucidate essential
      ecological mechanisms underlying polyploid adaptation to heterogeneous
      environments, and provide an important insight into the prevalence and
      persistence of polyploid plants.

PMID- 30281802
TI  - Peanut allergy - individual molecules as a key to precision medicine.
AB  - Peanut allergy is one of the most severe food allergies affecting millions of
      individuals worldwide. In German-speaking countries, peanut allergy is the most
      important cause of anaphylaxis in children and adolescents. This Editorial
      highlights the impact of individual peanut allergens on the severity of symptoms
      and summarizes the allergens' biological characteristics and usefulness as tools
      for precision diagnostic tests. This article is protected by copyright. All
      rights reserved.

PMID- 30281803
TI  - Methods of Assessment of the Corneas of the Eyes Laboratory Rabbits Exposed to
      Solar Ultraviolet-B Radiation.
AB  - The goal of this review was to identify and discuss the specialized methods that
      have been used to assess the corneas of the eyes of living rabbits exposed to the
      damaging effects of ultraviolet-B (UV-B). From publications reviewed between 1916
      and 2018, both albino and pigmented rabbits were used, usually being young adults
      weighing between 2 and 2.5 kg, and with many recent studies carried out under
      sedation. Older assessments were generally based on the use of in vivo slitlamp
      examinations, sometimes with the use of fluorescein or rose bengal to identify
      damaged cells, supported by light microscopy (histology) of excised corneas. In
      later years (after 1960), these structural studies have included in vivo and ex
      vivo specular microscopy, transmission and scanning electron microscopy as well
      as impression cytology. Early studies included measurements of the thickness of
      excised corneal specimens but in vivo pachymetry methods were widely used from
      the 1980s. Other assessments have included measurement of light transmission
      spectra of excised corneas, measures of metabolites in isolated corneas or
      staining corneal specimens for enzyme activities. While a wide range of
      specialized methods have been used, most of them have provided only descriptions
      of the effects of UV-B.

PMID- 30281804
TI  - Nicotinamide nucleotide transhydrogenase is required for brain mitochondrial
      redox balance under hampered energy substrate metabolism and high-fat diet.
AB  - Among mitochondrial NADP-reducing enzymes, nicotinamide nucleotide
      transhydrogenase (NNT) establishes an elevated matrix NADPH/NADP+ by catalyzing
      the reduction of NADP+ at the expense of NADH oxidation coupled to inward proton
      translocation across the inner mitochondrial membrane. Here, we characterize NNT
      activity and mitochondrial redox balance in the brain using a congenic mouse
      model carrying the mutated Nnt gene from the C57BL/6J strain. The absence of NNT
      activity resulted in lower total NADPH sources activity in the brain mitochondria
      of young mice, an effect that was partially compensated in aged mice. Nonsynaptic
      mitochondria showed higher NNT activity than synaptic mitochondria. In the
      absence of NNT, an increased release of H2 O2 from mitochondria was observed when
      the metabolism of respiratory substrates occurred with restricted flux through
      relevant mitochondrial NADPH sources or when respiratory complex I was inhibited.
      In accordance, mitochondria from Nnt-/- brains were unable to sustain NADP in its
      reduced state when energized in the absence of carbon substrates, an effect
      aggravated after H2 O2 bolus metabolism. These data indicate that the lack of NNT
      in brain mitochondria impairs peroxide detoxification, but peroxide
      detoxification can be partially counterbalanced by concurrent NADPH sources
      depending on substrate availability. Notably, only brain mitochondria from Nnt-/-
      mice chronically fed a high-fat diet exhibited lower activity of the redox
      sensitive aconitase, suggesting that brain mitochondrial redox balance requires
      NNT under the metabolic stress of a high-fat diet. Overall, the role of NNT in
      the brain mitochondria redox balance especially comes into play under
      mitochondrial respiratory defects or high-fat diet.

PMID- 30281805
TI  - Impact of route of administration on genotoxic oestrogens concentrations using
      oral vs transdermal oestradiol in girls with Turner syndrome.
AB  - OBJECTIVE: The established link between oestrogen and breast cancer occurs via
      both oestrogen receptor (ER)-mediated and non ER-mediated mechanisms. The term
      genotoxic estrogens describes mutagenic metabolites, including oestrogen
      catechols and quinones, which have been linked to breast carcinogenesis in post
      menopausal women. We aimed to assess whether the route of administration of
      17beta oestradiol (E2 ) affects the accumulation of genotoxic oestrogen
      metabolites in a model of ovarian failure in young girls with Turner syndrome.
      METHODS: Stored plasma samples obtained at 0 and 12 months were used from 40
      adolescents with Turner syndrome who participated in a 12 months randomized
      controlled trial of the metabolic impact of E2 orally (2 mg/d) vs transdermally
      (100 ug/d); dose escalation allowed matching of unconjugated E2 levels in the
      parent study. We measured 12 oestrogen metabolites (total concentrations =
      conjugated and unconjugated) using a highly sensitive LCMSMS assay. Results from
      48 normally menstruating adolescents were used for comparison. RESULTS: After
      treatment, least square mean (SE) total E2 concentrations were higher in the oral
      vs transdermal group (6784 pmol/L vs 1123 [1614], P < 0.0001), as was oestrone
      (E1 ) (91 060 pmol/L vs 19 278 [16 534], P < 0.0001). Also, higher after oral
      treatment were catechol-oestrogens 4-hydroxy-E2 (149 vs 28 [+/-49] pmol/L), 2
      hydroxy-E2 (300 vs 76 [+/-52]), 4-hydroxy-E1 (450 vs 105 [+/-113]), 2-hydroxy-E1
      (3094 vs 740 [+/-684]) and 16alpha-hydroxy-E1 (3,007 vs 157 [+/-534]) (<0.001
      between groups). Levels were much closer to controls in the transdermal group.
      CONCLUSIONS: Common feminizing doses of oral oestradiol for 12 months result in
      substantial accumulation of unphysiologic, genotoxic oestrogens compared to
      transdermal oestradiol, expanding concerns about oral oestrogens' first hepatic
      passage. Further studies assessing long-term risks of these metabolites in women
      taking different forms of oestrogen are needed.

PMID- 30281806
TI  - Deceased Pediatric Donor Livers: How Current Policy Drives Allocation and
      Transplantation.
AB  - BACKGROUND AND AIMS: Each year, approximately 60 children, representing 12% of
      waitlist candidates, die awaiting liver transplantation. The current allocation
      algorithm for pediatric donor livers prioritizes local/regional adults over
      national children. We attempted to better understand the impact of the present
      algorithm on pediatric candidates. METHODS: We analyzed pediatric donor liver
      offers from 2010 to 2014. Donors and recipients were classified based on age. We
      mapped allocation and acceptance patterns, and used subgroup analyses to explore
      the significance of Donor Service Areas (DSAs) with low pediatric transplant
      volumes. We used Cox proportional hazard regressions to evaluate post
      transplantation outcomes. RESULTS: 3,318 pediatric donor livers were transplanted
      into 3,482 recipients, 45% (1,569) were adults. Of the 1,569 adults, 25% (390)
      were received a pediatric organ that was never offered to children. 52% (204) of
      these 390 pediatric organs originated in the 37 DSAs with <=25 pediatric liver
      transplantations. 278 children died or were delisted due to illness during the
      same time with higher mortality rates in the 37 DSAs (10% versus 6%, p<0.01).
      Compared to adults, pediatric recipients aged <12 years had lower risks of post
      transplant mortality (HR0.62, 95%CI0.46-0.81, p<0.01). CONCLUSIONS: We found that
      45% of pediatric donor livers were transplanted into adults: 390 adults were
      transplanted with pediatric organs never offered to children access while 278
      children died or were delisted due to illness. This was more apparent in DSAs
      with low pediatric transplant volumes. We advocate for a change to allocation
      policies to allow pediatric organs to be offered to national children with status
      1B or MELD/PELD >15 before being offered to Local/Regional + Circle non-status 1A
      adults. This article is protected by copyright. All rights reserved.

PMID- 30281807
TI  - Prevalence characteristics of single and multiple HPV infections in women with
      cervical cancer and precancerous lesions in Beijing, China.
AB  - We assessed the prevalence characteristics of single and multiple high-risk human
      papillomavirus (HR-HPV) infections. A total of 1783 women who underwent
      colposcopy and cervical biopsy for abnormal ThinPrep Cytology Test and/or HR-HPV
      subtype genotyping results were enrolled in the study. Among the participants,
      770 were diagnosed with cervicitis, 395 with cervical intraepithelial neoplasia
      grade 1 (CIN1), 542 with CIN2-3, and 76 with squamous cell carcinoma (SCC), with
      HR-HPV infection rates of 75.8%, 85.8%, 95.9%, and 88.4%, respectively. The
      prevalence of total and multiple HR-HPV infections exhibited a bimodal age
      distribution with a peak at <=25 years, a decline with age and a second peak at
      >=55 years, whereas single HR-HPV infections exhibited one peak from 35 to 44
      years. The four most dominant HPV genotypes were HPV 16 (29.5%), 52 (15.0%), 58
      (14.2%), and 18 (10.4%). In total, 67.0%, 70.4%, and 82.1% of patients with CIN1,
      CIN2-3, and SCC, respectively, had a single HR-HPV infection, which increased
      significantly with the aggravation of the cervical lesion grade (P = 0.045).
      Patients with a single HPV 16 infection had higher incidences of CIN2+ (62.2%)
      than those with multiple HPV 16 infections (52.4%) (P = 0.021). Patients
      coinfected with HPV 16 had higher CIN2+ incidence than those with single HPV 52,
      31, 33, 35, 39, 45, 51, 56, or 59 infections (P < 0.001). This study provided
      baseline data on the prevalence characteristics of single and multiple HR-HPV
      infections in women attending a gynecological outpatient clinic in Beijing.

PMID- 30281809
TI  - LXRalpha Promotes Hepatosteatosis in Part via Activation of MicroRNA-378
      Transcription and Inhibition of Ppargc1beta Expression.
AB  - : Non-alcoholic fatty liver disease (NAFLD) is a major risk factor of many end
      stage liver diseases. Alterations in microRNA expression have been reported in
      NAFLD patients. However, the transcriptional mechanism(s) of dysregulated
      microRNAs under the state of NAFLD is poorly described; and microRNAs that
      regulate the pathogenesis of NAFLD synergistically with their regulators remain
      unknown. Here we report that microRNA-378 expression is significantly increased
      in fatty livers of mice and NAFLD patients. Although microRNA-378 locates within
      the intron of Ppargc1beta (Peroxisome proliferator-activated receptor gamma
      coactivator 1-beta), there was a significant uncoupling of Ppargc1beta mRNA and
      microRNA-378 levels in both sources of fatty livers. Further studies identified a
      full-length primary transcript of microRNA-378 (pri-miR-378). LXRalpha (Liver X
      receptor alpha) functioned as a transcription activator of microRNA-378 and a
      repressor of Ppargc1beta transcription. It is known that miR-378 is an inhibitor
      of fatty acid oxidation (FAO) and the function of Ppargc1beta is opposite to that
      of miR-378. GW3965 treatment (LXRalpha agonist) of murine hepatocytes and mice
      increased microRNA-378 and reduced Ppargc1beta, which subsequently impaired FAO
      and aggravated hepatosteatosis; while additional treatment of miR-378 inhibitor
      or Ppargc1beta, which knocked down increased miR-378 or recovered expression of
      Ppargc1beta, offset the effects of GW3965. Liver-specific ablation of Lxralpha
      led to decreased miR-378 and increased Ppargc1beta, which subsequently improved
      FAO and reduced hepatosteatosis. CONCLUSIONS: our findings indicated that miR-378
      possesses its own transcription machinery, which challenges the well-established
      dogma that miR-378 transcription is controlled by the promoter of Ppargc1beta.
      LXRalpha selectively activates transcription of miR-378 and inhibits expression
      of Ppargc1beta, which synergistically impairs FAO. In addition to lipogenesis,
      impaired FAO by miR-378 in part contributes to LXRalpha-induced hepatosteatosis.
      This article is protected by copyright. All rights reserved.

PMID- 30281808
TI  - Group movements in response to competitors' calls indicate conflicts of interest
      between male and female grey-cheeked mangabeys.
AB  - Long-distance vocalizations mediate spacing patterns by allowing groups to choose
      whether to draw close enough to a neighbor to initiate a short-range interaction.
      It is unclear, however, whether the patterning of calls and the resulting
      movements are invariant or change in response to social and ecological variables.
      In this study, we compare the impact of long-distance calls on neighboring
      groups' movements in two populations of grey-cheeked mangabeys (Lophocebus
      albigena) in Uganda, which differed widely in group density and food
      availability. We monitored movement responses of target groups to both naturally
      occurring and experimentally simulated "whoop-gobble" vocalizations of
      neighboring adult males to test whether responses indicated mate and food
      defense. When defending access to fertile females, males might coerce group
      members to move away from neighboring males; when defending fitness-limiting food
      resources, however, groups might approach and attempt to evict neighbors.
      Controlling for pre-call movement prior to the vocalization, we found no
      difference in group responses between the low- and high-density populations, and
      little support for either form of defense. Mangabey groups generally continued
      moving in their original direction, albeit at a slower pace, and deviations from
      this pattern were predictable: they avoided nearby callers but approached distant
      callers; they approached if the caller was in the area where home ranges
      overlapped; and approached when their own group contained multiple peak-estrous
      females. The effect of multiple fertile females potentially indicates a breakdown
      of male control as a result of within-group intrasexual mating competition, and
      greater-than-expected female control over travel movements. As suspected, grey
      cheeked mangabeys use neighbors' long-distance calls to maintain a spatial buffer
      between groups but changes in group movements indicate a conflict between male
      and female interests.

PMID- 30281810
TI  - One-year change in cognitive flexibility and fine motor function in middle-aged
      male and female marmosets (Callithrix jacchus).
AB  - The common marmoset (Callithrix jacchus) is uniquely suited for longitudinal
      studies of cognitive aging, due to a relatively short lifespan, sophisticated
      cognitive abilities, and patterns of brain aging that resemble those of humans.
      We examined cognitive function and fine motor skills in male and female marmosets
      (mean age ~5 at study entry) followed longitudinally for 2 years. Each year,
      monkeys were tested on a reversal learning task with three pairs of stimuli (n =
      18, 9 females) and a fine motor task requiring them to grasp small rewards from
      two staircases (Hill and Valley test, n = 12, 6 females). There was little
      evidence for a decline in cognitive flexibility between the two time points, in
      part because of practice effects. However, independent of year of testing,
      females took longer than males to reach criterion in the reversals, indicating
      impaired cognitive flexibility. Motivation was unlikely to contribute to this
      effect, as males refused a greater percentage of trials than females in the
      reversals. With regards to motor function, females were significantly faster than
      males in the Hill and Valley task. From Year 1 to Year 2, a slight slowing of
      motor function was observed in both sexes, but accuracy decreased significantly
      in males only. This study (1) demonstrates that marmosets exhibit sex differences
      in cognitive flexibility and fine motor function that resemble those described in
      humans; (2) that changes in fine motor function can already be detected at middle
      age; and (3) that males may experience greater age-related changes in fine motor
      skills than females. Additional data points will determine whether these sex and
      age differences persist over time.

PMID- 30281811
TI  - Reduction in a high-risk sex script among young urban women in the Love, Sex, &
      Choices web video HIV prevention intervention study.
AB  - For women, the high-risk sex script of condomless sex to maintain relationships
      with men is concerning, particularly in regard to heterosexual HIV acquisition.
      This secondary analysis of data from a clinical trial evaluated the effect of a
      12-episode, web-based video series intervention, entitled Love, Sex, and Choices,
      versus a text message control on lowering the high-risk sex script. The sample
      comprised 238 predominately urban Black women, ages 18-29, having HIV sex risk
      behavior. Data were collected at baseline and 6 months post-intervention. The Sex
      Script Video Response score was used to measure a high-risk sex script. HIV sex
      risk behavior was measured by Vaginal Equivalent Episodes with high-risk
      partners. At baseline, lower education, younger age at first sexual intercourse,
      and alcohol/non-injection drug use before sex were positively associated with a
      high-risk sex script. At baseline, as the high-risk sex script increased by one
      log unit, sex risk behavior increased by 0.47 log units (p < 0.001), equivalent
      to a 60% increase in the geometric mean of sex risk behavior. ANCOVA analysis
      indicated that from baseline to 6-months post intervention, lowering the high
      risk sex script by one unit was associated with an additional reduction of 0.26
      units in sex risk behavior. Compared to the text messages, the LSC video series
      was associated with a 27% greater reduction in the geometric mean of the sex
      script (p = 0.03). Further investigation into the effect of lowering sex scripts
      to reduce sex risk behavior is recommended.

PMID- 30281812
TI  - Full ablative versus fractional ablative laser therapy for Dowling-Degos disease.
AB  - Dowling-Degos disease (DDD) is a rare autosomal-dominant genodermatosis with
      limited treatment possibilities. Although the efficacy of ablative laser therapy
      has been reported, we sought to examine the efficacy of fractional versus full
      ablative laser therapy in a female patient with DDD in a split-side report. We
      treated the lesions on the right side of the patient's upper abdomen with an
      ablative fractional CO2 laser and the lesions on the left side of the upper
      abdomen with a full ablative Er:YAG laser (erbium-doped yttrium aluminium garnet
      laser) three times at monthly intervals. After three laser sessions, the lesions
      treated with the Er:YAG laser showed a complete response, whereas the fractional
      CO2 laser treatment was less effective. After the three treatments were
      performed, the right side of the patient's upper abdomen and portions of her
      lower abdomen and chest were also treated with the Er:YAG laser in full ablation
      mode with the same settings. After 1 year of follow up, there was no recurrence
      observed. Lasers Surg. Med. (c) 2018 Wiley Periodicals, Inc.

PMID- 30281813
TI  - Optimal frequency of tooth brushing in mechanically ventilated adults: Study
      protocol for a randomized controlled trial.
AB  - The optimal frequency of tooth brushing in the critically ill has not been
      experimentally determined. For mechanically ventilated patients, optimal
      frequency of tooth brushing is an important unresolved issue as there is little
      evidence to judge the benefits or associated risks of tooth brushing. Given this
      knowledge gap, the project's overall goal is to determine the optimal frequency
      of tooth brushing (once, twice, or three times daily) for mechanically ventilated
      adults. A prospective, randomized, experimental design is used. Specifically, 345
      subjects, with 207 expected to complete the study, are randomly assigned within
      36 hr of intubation to one of three groups (once, twice, or three times tooth
      brushing daily). Tooth brushing with a soft compact-head toothbrush takes
      approximately 2 min. Dental plaque assessment, gingival crevicular fluid (GCF)
      determination for IL-1beta, and data regarding healthcare-acquired infection
      (HAI) and clinical status are collected at baseline and daily in-hospital. The
      clinical impact of daily frequency of tooth brushing in relation to extent of
      dental plaque and inflammation reflected by GCF analysis will be compared by the
      three treatment arms. In addition, evaluation of safety for HAIs will be compared
      based on calculation of the number needed to harm. The trial will empirically
      determine the optimal frequency of tooth brushing in mechanically ventilated
      adults, balancing benefits and risks. This contribution is significant because it
      will have immediate impact on bedside nursing practice, and is a final component
      necessary for specific evidence-based guidelines for the common nursing
      intervention of oral care in mechanically ventilated adults.

PMID- 30281814
TI  - Oxytocin, vasopressin, and primate behavior: Diversity and insight.
AB  - It has become increasingly clear that the nonapeptide hormones oxytocin and
      vasopressin have more diverse behavioral and physiological effects across species
      and across individuals than was initially recognized. To reflect this variation,
      we would like to introduce our Special Issue, entitled Oxytocin and Vasopressin
      in Primate Behavior, by celebrating the diversity that is found across the
      articles within it. While every article directly addresses the topic of this
      Special Issue, they also vary in many characteristics: the species studied, the
      methods used, and the perspectives taken. By highlighting the interesting ways in
      which these articles differ from one another, we can gain unique insights into
      the subject that ties them together: our understanding of oxytocin and
      vasopressin and the behavior of primates. Nonhuman primates are critical
      intermediates between rodents and humans and are the best models for human
      biology and behavior, especially with respect to complex cognitive social
      constructs, such as visual social attention, face processing, and vocal
      communication. While rodent studies have laid an important and foundational
      framework for our understanding of nonapeptides, brains, and behavior, these
      studies cannot fully recapitulate human phenomena. Therefore, we hope the
      articles presented here contribute to a greater understanding on the role of
      oxytocin and vasopressin in primate physiology and behavior and help to further
      advance the application of this knowledge to human biology.

PMID- 30281815
TI  - DEAD Box Protein 5 Inhibits Liver Tumorigenesis by Stimulating Autophagy via
      Interaction with p62/SQSTM1.
AB  - : In hepatocellular carcinoma (HCC), dysregulated expression of DDX5 (DEAD box
      protein 5) and impaired autophagy have been reported separately. However, the
      relationship between them has not been explored. Here we present evidence to show
      that, by interacting with autophagic receptor p62, DDX5 promotes autophagy and
      suppresses tumorigenesis. DDX5 inversely correlated with p62/sequestosome 1
      (SQSTM1) expression in HBV-associated and non-HBV associated HCCs. Patients with
      low DDX5 expression showed poor prognosis after tumor resection. We found that
      DDX5 overexpression induced, while DDX5 knockdown attenuated autophagic flux in
      HepG2 and Huh7 cells. DDX5 promoted p62 degradation and markedly reduced the half
      life of p62. Moreover, DDX5 overexpression dramatically reduced while DDX5
      knockdown promoted cancer cell growth and tumorigenesis in vitro and in vivo. We
      found that DDX5 bound to p62 and interfered with p62/TRAF6 (TNF receptor
      associated factor 6) interaction. Further findings revealed that the N-terminal
      domain of DDX5, involved in the interaction with p62, was sufficient to induce
      autophagy independent of its RNA binding and helicase activity. DDX5
      overexpression decreased p62/TRAF6 mediated lysine 63-linked ubiquitination of
      mTOR, and subsequently inhibited the mTOR signaling pathway. Knockdown of TRAF6
      blocked DDX5-induced autophagy. Furthermore, we showed that the miR-17-5p
      downregulated DDX5 and impaired autophagy. Inhibition of miR-17-5p promoted
      autophagic flux and suppressed tumor growth in HCC xenograft models. CONCLUSION:
      Our findings define a non-canonical pathway that links miR-17-5p, DDX5,
      p62/TRAF6, autophagy and HCC. These findings open a new avenue for the treatment
      of HCC. This article is protected by copyright. All rights reserved.

PMID- 30281816
TI  - Letter to editor: Terlipressin is superior to noradrenaline in the management of
      acute kidney injury in acute-on-chronic liver failure.
AB  - We read with interest the paper by Arora et al. comparing terlipressin with
      noradrenaline in the management of acute kidney injury (AKI) in patients with
      acute-on-chronic liver failure (ACLF). The authors designed a randomized
      controlled trial to compare the response to therapy, course and outcomes between
      the two drugs. We agree with most of their observations, but we would like some
      more clarity regarding their conclusions. This article is protected by copyright.
      All rights reserved.

PMID- 30281817
TI  - Scars on plants sourced for termite fishing tools by chimpanzees: Towards an
      archaeology of the perishable.
AB  - Chimpanzees are well-studied, but raw material acquisition for tool use is still
      poorly understood as sources are difficult to trace. This study pioneers the use
      of information that can be gleaned from plant scars made by chimpanzees while
      they source vegetation parts to manufacture termite fishing tools. Source plant
      species, raw material types and locations relative to targeted termite mounds
      were recorded for populations at Gombe, Issa, and Mahale in western Tanzania.
      Recovered bark, twig, and vine tools were traced to 29 plant species, while grass
      sources were indeterminable. Bark extraction scars remained detectable for
      months, and thus possibly for as long as the plant is alive, while twig and vine
      scars preserved for a few weeks only. Scars preserve better than tools, given
      that twice as many plant species could be linked to the former than to the
      latter. Some source species were exploited across all sites for the same type of
      tool material, while two species were sourced for different types. Compared to
      apes at Gombe and Mahale, Issa chimpanzees carried material from twice as far
      away, perhaps because the Issa habitat is more open and dry, which entails
      greater distances between suitable raw material sources and targeted mounds. Site
      specific tools were based on different raw materials, in two cases sourced from
      the same species, which could suggest learned preferences for particular tool
      material. "Archaeology of the perishable" as pioneered in this study broadens the
      methodological approach of the wider field of primate archaeology to include
      reconstructions of past animal behavior associated with the production of plant
      based tools.

PMID- 30281818
TI  - Psychometric testing of the short-form Chinese version of the self-management for
      adolescents with type 1 diabetes scale.
AB  - Self-management among adolescents with type 1 diabetes (T1D) is poorer than in
      other age groups during childhood. A valid and reliable short-form scale to
      measure self-management in adolescents with T1D is prudent for enhancing their
      self-management in clinical settings. We used a cross-sectional design to develop
      a short-form Chinese version of the Self-Management of Type 1 Diabetes for
      Adolescents Scale (C-SMOD-A) and test its psychometric characteristics. Two
      hundred adolescents with T1D were recruited from four hospitals in Taiwan through
      convenience sampling. Content validity, exploratory factor analysis, and
      corrected item-total correlations were used to shorten the 52-item C-SMOD-A.
      Confirmatory factor analysis, criterion-related validity, and reliability testing
      were used to examine the psychometric characteristics of the short-form C-SMOD-A.
      Finally, the 23-item C-SMOD-A (C-SMOD-A-23) with five inter-correlated factors
      was developed. Glycated hemoglobin levels were significantly associated with each
      subscale of the C-SMOD-A-23 with correlation coefficients ranging from -0.18 to 
      0.31. The composite reliability and test-retest reliability of the five subscales
      ranged from 0.70 to 0.88 and from 0.78 to 0.93 respectively. Accordingly, the C
      SMOD-A-23 has acceptable validity and reliability to measure five specific
      domains of self-management for adolescents with T1D. Health-care providers could
      use the C-SMOD-A-23 as a clinical reference to assess specific domains of self
      management and provide interventions to enhance self-management for adolescents
      with T1D.

PMID- 30281819
TI  - A computational method to characterize the missense mutations in the catalytic
      domain of GAA protein causing Pompe disease.
AB  - Pompe disease is an autosomal recessive lysosomal storage disease caused by acid
      alpha-glucosidase (GAA) deficiency, resulting in intralysosomal accumulation of
      glycogen, including cardiac, skeletal, and smooth muscle cells. The GAA gene is
      located on chromosome 17 (17q25.3), the GAA protein consists of 952 amino acids;
      of which 378 amino acids (347-726) falls within the catalytic domain of the
      protein and comprises of active sites (518 and 521) and binding sites (404, 600,
      616, and 674). In this study, we used several computational tools to classify the
      missense mutations in the catalytic domain of GAA for their pathogenicity and
      stability. Eight missense mutations (R437C, G478R, N573H, Y575S, G605D, V642D,
      L705P, and L712P) were predicted to be pathogenic and destabilizing to the
      protein structure. These mutations were further subjected to phenotyping analysis
      using SNPeffect 4.0 to predict the chaperone binding sites and structural
      stability of the protein. The mutations R437C and G478R were found to compromise
      the chaperone-binding activity with GAA. Molecular docking analysis revealed that
      the G478R mutation to be more significant and hinders binding to the DNJ
      (Miglustat) compared with the R437C. Further molecular dynamic analysis for the
      two mutations demonstrated that the G478R mutation was acquired higher deviation,
      fluctuation, and lower compactness with decreased intramolecular hydrogen bonds
      compared to the mutant R437C. These data are expected to serve as a platform for
      drug design against Pompe disease and will serve as an ultimate tool for variant
      classification and interpretations.

PMID- 30281820
TI  - Opportunities and challenges for intranasal oxytocin treatment studies in
      nonhuman primates.
AB  - Nonhuman primates provide a human-relevant experimental model system to explore
      the mechanisms by which oxytocin (OT) regulates social processing and inform its
      clinical applications. Here, we highlight contributions of the nonhuman primate
      model to our understanding of OT treatment and address unique challenges in
      administering OT to awake behaving primates. Prior preclinical research utilizing
      macaque monkeys has demonstrated that OT can modulate perception of other
      individuals and their expressions, attention to others, imitation, vigilance to
      social threats, and prosocial decisions. We further describe ongoing efforts to
      develop an OT delivery system for use in experimentally naive juvenile macaque
      monkeys compatible with naturalistic social behavior outcomes. Finally, we
      discuss future directions to further develop the rhesus monkey as a preclinical
      test bed to evaluate the effects of OT exposure and advance efforts to translate
      basic science OT research into safe and effective OT therapies.

PMID- 30281821
TI  - Transcranial direct-current stimulation reduces nociceptive behaviour in an
      orofacial pain model.
AB  - BACKGROUND: Transcranial direct-current stimulation (tDCS) is a noninvasive
      method of brain stimulation suggested as a therapeutic tool for pain and is
      related to the reversal of maladaptive plasticity associated with chronic pain.
      OBJECTIVES: This study investigated the effect of tDCS, a non-pharmacological
      therapy, on local mechanical hyperalgesia, and remote thermal hyperalgesia in
      rats submitted to orofacial inflammatory pain model, by facial von Frey and hot
      plate tests, respectively. In addition, we evaluated levels of BDNF, NGF, IL-10
      and IL-6 in the brainstem and blood serum of these animals at 24 hours and 7 days
      after the end of tDCS treatment. METHODS: Rats were subjected to
      temporomandibular joint pain and treated with tDCS. The animals were divided into
      control, pain and pain + treatment groups. Mechanical and thermal hyperalgesia
      were evaluated at baseline, 7 days after administration of complete Freund's
      adjuvant, and immediately, 24 hours, and 7 days after the tDCS treatment.
      Neuroimmunomodulators levels were determined by ELISA. Statistical analyses were
      performed by (GEE)/Bonferroni (behavioural tests), three-way ANOVA/SNK
      (neurochemical tests) and Kruskal-Wallis (histological analysis). RESULTS:
      Transcranial direct-current stimulation reduced mechanical and thermal
      hyperalgesia (P < 0.01). We observed interaction between factors (pain and
      treatment) increasing brainstem BDNF (P < 0.01) and NGF (P < 0.05) levels.
      Furthermore, we found an increase in IL-6 and IL-10 levels in the brainstem at 24
      hours and 7 days after tDCS, respectively. CONCLUSION: We showed that tDCS
      reduces thermal and mechanical hyperalgesia induced by orofacial pain until 7
      days after treatment. These findings demonstrate that tDCS was effective in the
      control of orofacial inflammatory pain.

PMID- 30281823
TI  - Combined effect of anti-high-mobility group box-1 monoclonal antibody and
      peramivir against influenza A virus-induced pneumonia in mice.
AB  - Human pandemic H1N1 2009 influenza virus causes significant morbidity and
      mortality with severe acute lung injury due to the excessive inflammatory
      reaction, even with neuraminidase inhibitor use. The anti-inflammatory effect of
      anti-high-mobility group box-1 (HMGB1) monoclonal antibody (mAb) against
      influenza pneumonia has been reported. In this study, we evaluated the combined
      effect of anti-HMGB1 mAb and peramivir against pneumonia induced by influenza A
      (H1N1) virus in mice. Nine-week-old male C57BL/6 mice were inoculated with H1N1
      and treated with intramuscularly administered peramivir at 2 and 3 days post
      infection (dpi). The anti-HMGB1 mAb or a control mAb was administered at 2, 3,
      and 4 dpi. Survival rates were assessed, and lung lavage and pathological
      analyses were conducted at 5 and 7 dpi. The combination of peramivir with the
      anti-HMGB1 mAb significantly improved survival rate whereas the anti-HMGB1 mAb
      alone did not affect virus proliferation in the lungs. This combination therapy
      also significantly ameliorated histopathological changes, neutrophil
      infiltration, and macrophage aggregation by inhibiting HMGB1, inflammatory
      cytokines, and oxidative stress. Fluorescence immunostaining showed that the anti
      HMGB1 mAb inhibited HMGB1 translocation from type I alveolar epithelial cells. In
      summary, combining anti-HMGB1 with conventional anti-influenza therapy might be
      useful against severe influenza virus infection.

PMID- 30281822
TI  - Dispersal and female philopatry in a long-term, stable, polygynous gibbon
      population: Evidence from 16 years field observation and genetics.
AB  - Gibbons are generally reported to live in small socially monogamous family groups
      in which both sexes disperse when they reach maturity. For the first time, we
      documented the dispersal pattern in a population of gibbons living in stable
      polygynous groups (Nomascus concolor) integrating 16 years' field observation and
      genetic information from fecal DNA. All subadult males except for one dispersed
      at 9.8 +/- 1.4 years of age (range: 8-12, N = 10). The last male remained in his
      natal group and obtained the breeding position at age 11 by evicting the original
      dominant male. Females reached sexual maturity (as evidenced by the change in
      body color from black to yellow) at 8 years (N = 4). Three of them dispersed and
      one obtained a position as a breeding female and bred in her natal group. We also
      observed one female returning to her natal group with her infant after her
      presumed father was taken over by a neighboring male. We identified only three
      mtDNA haplotypes from 22 individuals at Dazhaizi. Individuals in one group shared
      the same haplotype, with only one exception. Genetic results showed that the two
      breeding females were mother-daughter pairs in all three study groups at the end
      of this study, implying some degree of female philopatry. We argue that in the
      case of black crested gibbons, dispersal decisions appear to represent highly
      opportunistic events in response to reproductive opportunities in their natal and
      neighboring groups.

PMID- 30281824
TI  - The efficacy of nasal airway stent (Nastent) on obstructive sleep apnoea and
      prediction of treatment outcomes.
AB  - BACKGROUND: Obstructive sleep apnoea (OSA) is characterised by recurrent episodes
      of partial or complete upper airway collapse during sleep and is highly prevalent
      in the general population. The nasopharyngeal airway stent (Nastent) is a
      specifically designed, preformed silicone tube that intends to maintain the upper
      airway patency during sleep and reduce snoring and sleep apnoea. OBJECTIVE(S):
      The purpose of this study was to determine the efficacy of Nastent treatment and
      examine predictors for Nastent treatment outcomes in patients with OSA. METHODS:
      Consecutive thirty patients were enrolled in this study. Cephalometric
      radiographs were obtained to analyse the pharyngeal and craniofacial morphology.
      Before and after Nastent treatment, we evaluated OSA using a portable sleep
      study. RESULTS: Twenty-nine subjects completed this study. There were significant
      decreases in the respiratory event index (REI) (22.4 +/- 14.1 to 15.7 +/- 10.4, P
      < 0.01) and a significant increase in the lowest SpO2 (81.9 +/- 7.5 to 86.6 +/-
      4.8, P < 0.01) by Nastent treatment. Subjects were divided into responders and
      non-responders based on reduction in REI of >50% compared with baseline REI. We
      evaluated the ratio of inferior airway width and middle airway width (IAW/MAW) on
      cephalograms as the index of the narrowest airway site. The IAW/MAW was
      significantly higher in responders than in non-responders (1.4 +/- 0.9 vs 0.9 +/-
      0.4, P < 0.01) and predicted treatment responders with high accuracy
      (sensitivity: 90.9%, specificity: 88.9%, when IAW/MAW was set at 1.10).
      CONCLUSIONS: The Nastent device improved OSA, and a narrower velopharynx than
      hypopharynx predicted treatment response with a good sensitivity and specificity.

PMID- 30281825
TI  - Standard growth and diarrhea-associated growth faltering in captive infant rhesus
      macaques (Macaca mulatta).
AB  - Reference growth studies of captive rhesus macaque infants have not accounted for
      diarrhea and the potential for growth stunting or growth faltering. Healthy
      infants without diarrhea could be used to build a standard growth chart and a
      tool used to detect growth faltering associated with diarrhea. We hypothesized
      infants who develop diarrhea during the first year of life would experience
      decreased linear weight gain compared to healthy infants, and we used healthy
      infants to establish standard growth of male and female infants. We hypothesized
      the lower 3rd percentile of standard growth would be cut-off criteria used in
      screening for diarrhea-associated growth faltering. Using a retrospective cohort
      of 6,510 infant weight records in a multiple linear regression, daily weight gain
      through the first year of life was determined by sex, housing type, and health
      status. Male standard growth was 4.1 g/day (95%CI: 4.0-4.2 g/day) in corrals and
      4.7 g/day (95%CI: 4.5-4.8 g/day) in shelter housing. Female standard growth was
      4.0 g/day (95%CI: 3.8-4.2 g/day) in corrals and 4.4 g/day (95%CI: 4.0-4.7 g/day)
      in shelter housing. Diarrhea was significantly associated with decreased linear
      weight gain by up to 34% during the first year of life. Odds of growth faltering
      of infants, defined as those falling below the 3rd percentile of standard growth,
      were at least 8.9 higher given a history of diarrhea compared to healthy. The
      growth faltering cut-off criteria had a sensitivity of at least 53% for males and
      females to screen for diarrhea in infants between 6 and 12 months in shelters
      housing. Interinstitutional collaborations of infant rhesus macaque weight
      records would refine the standard growth charts and cut-off criteria, and
      additional morphometric data would provide a more nuanced picture of growth
      stunting.

PMID- 30281826
TI  - Orofacial pain and its potential oral causes in older people with mild cognitive
      impairment or dementia.
AB  - BACKGROUND: The number of people with dementia and natural dentition is growing.
      As dementia progresses, the degree of self-care decreases and the risk of oral
      health problems and orofacial pain increases. OBJECTIVES: To examine and compare
      the presence of orofacial pain and its potential causes in older people with Mild
      Cognitive Impairment (MCI) or dementia. METHODS: In this cross-sectional
      observational study, the presence of orofacial pain and its potential causes was
      studied in 348 participants with MCI or dementia with all levels of cognitive
      impairment in two outpatient memory clinics and ten nursing homes. RESULTS:
      Orofacial pain was reported by 25.7% of the 179 participants who were considered
      to present a reliable pain self-report (Mini-Mental State Examination score >=14
      points), while it could not be determined in people with more severe cognitive
      impairment. The oral health examination of the 348 participants indicated that
      potential painful conditions, such as coronal caries, root caries, tooth root
      remnants or ulcers were present in 50.3%. There was a significant correlation
      between the level of cognitive impairment and the number of teeth, r = 0.185, P =
      0.003, teeth with coronal caries, r = -0.238, P < 0.001, and the number of tooth
      root remnants, r = -0.229, P = 0.004, after adjusting for age. CONCLUSIONS: This
      study indicated that orofacial pain and its potential causes were frequently
      present in participants with MCI or dementia. Therefore, a regular oral
      examination by (oral) healthcare providers in people with MCI or dementia remains
      imperative, even if no pain is reported.

PMID- 30281827
TI  - Social behavioral correlates of Kaposi sarcoma-associated herpesvirus infection
      among Han and Uygur populations in Xinjiang, China.
AB  - BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) is endemic in Xinjiang,
      China and its prevalence varies considerably across ethnic groups. The current
      study explored the prevalence and correlates of KSHV infection among Han and
      Uygur populations in Xinjiang. METHODS: A cross-sectional study, including 282
      Han ethnicity and 312 Uygur, was conducted in Xinjiang, China. All participants
      underwent face to face questionnaire interview. Plasma samples were collected and
      screened for KSHV infection using immunofluorescence assay. Univariate and
      multivariate analyses were conducted to examine the correlates of KSHV
      seropositivity. RESULTS: The KSHV seroprevalence was 41.6% (95% confidence
      interval [CI], 37.6-45.6) overall and was higher in the Uygur group (59.9%; 95%
      CI, 54.3-65.4) than the Han group (21.3%; 95% CI, 16.6-26.5). A significant
      difference in the geometric mean titer (GMT) of the KSHV antibodies was detected
      between the Uygur and Han groups (158.2; interquartile range [IQR], 80-320 vs
      89.1; IQR, 40-160; P < 0.001). After adjusting for potential confounders, Uygur
      ethnicity (odds ratios [OR], 5.96; 95% CI, 4.05-8.90), age greater than or equal
      to 50 years (OR, 1.84; 95% CI, 1.24-2.77), and preference for meat diet (OR,
      2.15; 95% CI, 1.05-4.46) were significantly associated with increased odds of
      KSHV seropositivity. CONCLUSION: The study demonstrated high prevalence and
      correlates of KSHV infection in both Han and Uygur populations in Xinjiang,
      China. There is an urgent need for programmatic adaptation to address primary
      prevention interventions of KSHV infection in this endemic region.

PMID- 30281828
TI  - Editorial: less acid, less cancer? Is this the question? Authors' reply.

PMID- 30281829
TI  - Editorial: proton pump inhibitors (PPIs) and microscopic colitis.

PMID- 30281830
TI  - Letter: identifying coeliac disease among patients with bloating-Authors' reply.

PMID- 30281831
TI  - Letter: screening for adrenal suppression in paediatric inflammatory bowel
      disease.

PMID- 30281833
TI  - Editorial: clinical features and outcomes of hepatocellular carcinoma in
      Caucasian cirrhotic patients on long-term analogue therapy for HBV.

PMID- 30281834
TI  - Letter: proton pump inhibitors use and risk of hepatocellular carcinoma: A meta
      analysis of observational studies.

PMID- 30281835
TI  - Editorial: a baseline tool for predicting response to peginterferon alfa-2a in
      HBeAg-positive patients-same score, different outcomes.

PMID- 30281836
TI  - Editorial: a baseline tool for predicting response to peginterferon alfa-2a in
      HBeAg-positive patients-same score, different outcomes. Author's Reply.

PMID- 30281832
TI  - Short and long-term effectiveness and safety of vedolizumab in inflammatory bowel
      disease: results from the ENEIDA registry.
AB  - BACKGROUND: Effectiveness of vedolizumab in real world clinical practice is
      unknown. AIM: To evaluate the short and long-term effectiveness of vedolizumab in
      patients with inflammatory bowel disease (IBD). METHODS: Patients who received at
      least 1 induction dose of vedolizumab were included. Effectiveness was defined
      based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo
      Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week
      14. Variables associated with short-term remission were identified by logistic
      regression analysis. The Kaplan-Meier method was used to evaluate the long-term
      durability of vedolizumab treatment. Cox model was used to identify factors
      associated with discontinuation of treatment and loss of response. RESULTS: 521
      patients were included (median follow-up 10 months [interquartile range 5-18
      months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs
      UC), previous surgery, higher CRP concentration and disease severity at baseline
      were significantly associated with impaired response. The rate of vedolizumab
      discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in
      CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP
      concentration were associated with lower durability of treatment. Seven per cent
      of patients developed adverse events, infections being the most frequent.
      CONCLUSIONS: Over 60% of IBD patients respond to vedolizumab. Many patients
      discontinue treatment over time. CD and disease burden impair both short- and
      long-term response. Vedolizumab seems to be safe in clinical practice.

PMID- 30281837
TI  - Letter: screening for adrenal suppression in paediatric inflammatory bowel
      disease - authors' reply.

PMID- 30281838
TI  - Letter: identifying coeliac disease among patients with bloating.

PMID- 30281839
TI  - Editorial: less acid, less cancer? Is this the question?

PMID- 30281840
TI  - Smoldering mastocytosis: Survival comparisons with indolent and aggressive
      mastocytosis.

PMID- 30281841
TI  - Evaluation of videoendoscopic examinations of arytenoid function in the 2-year
      old Thoroughbred: Can we all agree?
AB  - BACKGROUND: Upper respiratory tract (URT) endoscopic examination is a routine
      part of prepurchase examinations. Discrepancies have been documented in the
      assessment of arytenoid function grades (AFG) between veterinarians. OBJECTIVES:
      To document intra- and interobserver agreement for a population of multi
      experience level veterinarians for assessment of AFG of 2-year-old Thoroughbreds.
      STUDY DESIGN: Observational cohort study. METHODS: One-hundred and fourteen URT
      videoendoscopic examinations were evaluated by 10 veterinarians. Veterinarians
      were categorised based on experience, into five groups, each group with two
      veterinarians. Arytenoid function was graded using the Havemeyer ordinal scale
      and then reclassified by the authors dichotomously into 'meets conditions of
      sale' (MCS) or 'does not meet conditions of sale'(DNMCS). Interobserver agreement
      of arytenoid function was assessed across all 10 veterinarians using Fleiss'
      kappa and between veterinarians of similar experience levels in the five
      subgroups using Cohen's unweighted (k) and Cohen's linear weighted kappa (Ck).
      Intraobserver agreement was similarly calculated for each reviewer using 22
      repeated video clips. RESULTS: Overall interobserver agreement using ordinal
      scales was fair (k = 0.27, 95% CI 0.22-0.31) to moderate (mean weighted Ck =
      0.57, 95% CI 0.46-0.69) depending on statistical methodology used. Using the
      dichotomous classification, interobserver agreement was good (k = 0.7, 95% CI
      0.63-0.77). Overall intraobserver agreement using ordinal scales was fair (mean k
      = 0.26, 95% CI 0.14-0.38) to good (mean Ck = 0.61, 95% CI 0.50-0.71); and for the
      dichotomous reclassification it was good (k = 0.73, 95% CI 0.59-0.87). Experience
      level differences were identified. MAIN LIMITATIONS: The low number of
      veterinarians in each experience subgroup. CONCLUSIONS: Subjectivity exists in
      arytenoid function grading, despite the existence of a well-defined scale.
      Agreement variation exists depending on the grading scales and statistical
      methods used for analysis. Future studies pre- and post veterinarian training are
      indicated to determine if agreement can be improved.

PMID- 30281843
TI  - Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk
      stratification and management.
AB  - Disease Overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are
      myeloproliferative neoplasms respectively characterized by erythrocytosis and
      thrombocytosis; other disease features include leukocytosis, splenomegaly,
      thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic
      or fibrotic transformation. Diagnosis: Bone marrow morphology remains the
      cornerstone of diagnosis. In addition, the presence of JAK2 mutation is expected
      in PV while approximately 90% of patients with ET express mutually exclusive
      JAK2, CALR, or myeloproliferative leukemia mutations. In ET, it is most important
      to exclude the possibility of prefibrotic myelofibrosis. Survival: Median
      survivals are 14 years for PV and 20 years for ET; the corresponding values for
      younger patients are 24 and 33 years. Certain mutations (mostly spliceosome) and
      abnormal karyotype might compromise survival in PV and ET. Life-expectancy in ET
      is inferior to the control population. Driver mutations have not been shown to
      affect survival in ET. Risk of thrombosis is higher in JAK2-mutated ET. Leukemic
      transformation rates at 10 years are estimated at <1% for ET and 3% for PV.
      Thrombosis Risk: In PV, 2 risk categories are considered: high (age > 60 years or
      thrombosis history present) and low (absence of both risk factors); in ET, 4 risk
      categories are considered: very low (age <= 60 years, no thrombosis history, JAK2
      wild-type), low (same as very low but JAK2 mutation present), intermediate (age >
      60 years, no thrombosis history, JAK2 wild-type) and high (thrombosis history
      present or age > 60 years with JAK2 mutation). Risk-Adapted Therapy: The main
      goal of therapy in both PV and ET is to prevent thrombohemorrhagic complications.
      All patients with PV require phlebotomy to keep hematocrit below 45% and once- or
      twice-daily aspirin (81 mg), in the absence of contraindications. Very low-risk
      ET might not require therapy while aspirin therapy is advised for low-risk
      disease. Cytoreductive therapy is recommended for high-risk ET and PV but it is
      not mandatory for intermediate-risk ET. First-line drug of choice for
      cytoreductive therapy, in both ET and PV, is hydroxyurea and second-line drugs of
      choice are interferon-alpha and busulfan. We do not recommend treatment with
      ruxolutinib in PV, unless in the presence of severe and protracted pruritus or
      marked splenomegaly that is not responding to the aforementioned drugs.

PMID- 30281842
TI  - Special considerations for clinical trials in fibrodysplasia ossificans
      progressiva (FOP).
AB  - Clinical trials for orphan diseases are critical for developing effective
      therapies. One such condition, fibrodysplasia ossificans progressiva (FOP;
      MIM#135100), is characterized by progressive heterotopic ossification (HO) that
      leads to severe disability. Individuals with FOP are extremely sensitive to even
      minor traumatic events. There has been substantial recent interest in clinical
      trials for novel and urgently-needed treatments for FOP. The International
      Clinical Council on FOP (ICC) was established in 2016 to provide consolidated and
      coordinated advice on the best practices for clinical care and clinical research
      for individuals who suffer from FOP. The Clinical Trials Committee of the ICC
      developed a focused list of key considerations that encompass the specific and
      unique needs of the FOP community - considerations that are endorsed by the
      entire ICC. These considerations complement established protocols for developing
      and executing robust clinical trials by providing a foundation for helping to
      ensure the safety of subjects with FOP in clinical research trials.

PMID- 30281844
TI  - Relationship between serum level of growth differentiation factors 8, 11 and bone
      mineral density in girls with anorexia nervosa.
AB  - BACKGROUND: Adolescents with anorexia nervosa (AN) have low body mass and low
      bone mineral density (BMD). Growth differentiation factor 8 (Myostatin, GDF8) and
      its homologue growth differentiation factor 11 (GDF11), members of the TGF-beta
      super-family, play an important role in muscle regeneration and bone metabolism
      in healthy individuals. However, their association with BMD in AN is unknown. The
      present study was undertaken to investigate the relationship between GDF8, GDF11
      and BMD in adolescent girls with AN. METHODS: Serum GDF8, GDF11 and BMD were
      determined in 25 girls (12-16 years old) with AN and 31 healthy girls (12-16
      years old). RESULTS: Growth differentiation factor 8 levels were lower in AN
      subjects. On the contrary, GDF11 levels were higher in AN subjects than controls.
      There was no relationship between GDF8 and BMD. A significant negative
      correlation between GDF11 and BMD was found. In multiple linear stepwise
      regression analysis, BMI, 25-hydroxyvitamin D, GDF11, or lean mass, but not fat
      mass and GDF8, were independent predictors of BMD in the AN and control groups
      separately. CONCLUSIONS: Growth differentiation factor 11 was independent
      predictor of BMD in girls with AN. It suggested that GDF11 exerts a negative
      effect on bone mass.

PMID- 30281846
TI  - Abstracts of the 2018 International Congress of Parkinson's Disease and Movement
      Disorders(r).

PMID- 30281847
TI  - The Coordination Chemistry of Copper Uptake and Storage for Methane Oxidation.
AB  - Methanotrophs are remarkable bacteria that utilise large quantities of copper
      (Cu) to oxidize the potent greenhouse gas methane. To help provide the Cu they
      require for this process some methanotrophs can secrete the Cu-sequestering
      modified peptide methanobactin. These small molecules bind Cu(I) with very high
      affinity and crystal structures have provided insight into why this is the case,
      and also how the metal ion may be released within the cell. A much greater
      proportion of methanotrophs possess a member of a newly discovered bacterial
      family of copper storage proteins (the Csps). These are tetramers of four-helix
      bundles whose cores are lined with Cys residues enabling the binding of large
      numbers of Cu(I) ions. In methanotrophs, a Csp exported from the cytosol stores
      Cu(I) for the active site of the ubiquitous enzyme that catalyses the oxidation
      of methane. The presence of cytosolic Csps, not only in methanotrophs but in a
      wide range of bacteria, challenges the dogma that these organisms have no
      requirement for Cu in this location. The properties of the Csps, with an emphasis
      on Cu(I) binding and the structures of the sites formed, are the main focus of
      this review.

PMID- 30281845
TI  - Analysis of BAFF gene polymorphisms in UK Graves' disease patients.
AB  - OBJECTIVE: B lymphocyte activating factor (BAFF), a member of the tumour necrosis
      factor superfamily, is essential for B cell activation, differentiation and
      survival. Elevated circulating BAFF levels have been found in patients with
      several autoimmune conditions, including Graves' disease. In addition, BAFF gene
      variants have been associated with Graves' disease in a Taiwanese cohort, and
      with several other autoimmune conditions in non-Taiwanese populations. DESIGN AND
      METHODS: We performed a case-control association study to investigate two BAFF
      polymorphisms (rs9514828 and rs4000607) in a UK cohort of 444 patients with
      Graves' disease. Genotype frequencies were compared to those from 447 local
      controls and more than 5000 healthy controls from the Wellcome Trust case-control
      consortium (WTCCC2). RESULTS: There was a significant difference in the frequency
      of the AA genotype at rs4000607 between the Graves' disease cohort and both the
      local controls (P = 0.045) and the WTCCC2 controls (P = 4.56 * 10-6 ).
      Furthermore, the frequency of the A allele was found to be increased in the
      Graves' disease group compared to WTCCC2 controls (P = 0.02, OR 1.20 (95% CI 1.03
      1.41). No association was observed at the rs9514828 locus. CONCLUSION:
      Dysfunction of the humoral immune system is an obligatory pathophysiological
      component of Graves' disease, hence BAFF is an excellent functional candidate
      gene. We have demonstrated, for the first time, a significant association of the
      BAFF polymorphism rs4000607 with Graves' disease in a UK cohort. Further work to
      elucidate the role of BAFF in the pathogenesis of Graves' disease is now
      warranted.

PMID- 30281848
TI  - Small Changes With Big Consequences: Swapping Two Atoms In Side Chains Changes
      Phenylene-Ethynylene Packing And Fluorescence.
AB  - Engineering the properties of conjugated materials in the solid state is an
      unsolved, ongoing challenge important to fundamental understanding of how non
      covalent interactions dictate packing and key properties, as well as the
      development of technologies based in organic optoelectronics. The most common
      design paradigm of such materials divide them into a "main chain" with extended
      conjugation, the chemical structure of which determines optoelectronic
      properties, and "side chains" not conjugated to the backbone, which provide
      solubility when they are long alkyl chains. This paper describes comparisons
      between phenylene-ethynylene molecules in which slight changes to the structure
      of "side chains"-swapping hydrogen and fluorine atomic position on an aromatic
      ring-results in unexpectedly large changes in the solid-state optical properties.
      In a pair of anisyl-terminated three-ring phenylene-ethynylenes, switching the
      side chain arenes of benzyl esters from 2,4,6-trifluoro to 2,3,6-trifluoro
      results in a shift in fluorescence emission spectra of over 100 nm, as well as
      the opposite direction of force-induced shifting of emission. Through a
      combination X-ray crystal structures, electronic structure calculations, and
      comparisons with other derivatives, we describe how the 2,4,6-trifluorinated side
      chains yield cofacial fluoroarene-arene stacking interactions that twist the PE
      backbone out of conjugation, while the 2,3,6-trifluoro side chains do not stack,
      instead yielding more coplanar PE backbones that form intermolecular aggregates.
      Overall, this work demonstrates how slight modifications to parts of conjugated
      materials normally considered ancillary to optoelectronic properties can
      determine their solid-state properties, epitomizing the challenge of rational
      design but at the same time offering opportunities for materials discovery and
      improved understanding of non-covalent interactions.

PMID- 30281849
TI  - Immediate and early implant placement in single-tooth gaps in the anterior
      maxilla: A prospective study on ridge dimensional, clinical, and aesthetic
      changes.
AB  - OBJECTIVES: This prospective study evaluated the impact of timing of placement
      (immediate and early) on the horizontal ridge dimensional changes, clinical, and
      aesthetic outcomes of implants placed in single-tooth gaps in the anterior
      maxilla. MATERIALS AND METHODS: Implants were placed in single-tooth gaps in the
      anterior maxilla of 30 patients, either immediately after extraction (Group A, n
      = 15) or after a healing period of 4-8 weeks (Group B, n = 15). In both groups,
      implant placement was followed by a 3- to 4-month period of non-submerged
      healing, after which definitive crowns were placed. Study models were obtained
      before extraction (T0), at implant placement (T1), at the insertion of a
      definitive crown (T2), and 1-year thereafter (T3). Horizontal ridge dimensional
      changes were measured by superimposing the optical scans of the study models from
      different time-points. Radiographs and photographs were used to evaluate changes
      in marginal bone levels and soft tissue recession. Aesthetic evaluation was
      carried out using the Pink and White Esthetic Score (PES and WES) indices.
      Patient-reported outcomes were measured using a subjective questionnaire.
      RESULTS: A 100% implant survival rate was observed in both groups after a 1-year
      follow-up. Analysis showed a labial horizontal tissue dimensional change of 0.61
      mm and 0.72 mm from T0 to T3 in Groups A and B, respectively. Acceptable PES
      values were observed in both groups (Group A: 9.40; Group B: 9.27) after the 1
      year follow-up period. No incidence of advanced mucosal recession was observed
      between definitive crown insertion and 1-year follow-up in both groups. No
      significant changes were observed for all other measured variables at different
      time-points. CONCLUSIONS: Immediate and early placed implants in single-tooth
      gaps in the anterior maxilla showed similar ridge dimensional changes as well as
      acceptable clinical, aesthetic, and patient-centred outcomes in the short-term (1
      year follow-up).

PMID- 30281850
TI  - Consider the costs of aiding mild hearing loss in the absence of clear benefits:
      Response to McCreery and colleagues.

PMID- 30281851
TI  - Mild hearing loss is a developmental risk: Response to Carew and colleagues.

PMID- 30281852
TI  - Effects of Cutting the Sacrospinous and Sacrotuberous Ligaments.
AB  - The sacrospinous (SS) and sacrotuberous (ST) ligaments form a complex at the
      posterior pelvis, with an assumed role as functional stabilizers. Experimental
      and clinical research has yielded controversial results regarding their function,
      both proving and disproving their role as pelvic stabilizers. These findings have
      implications for strategies for treating pelvic injury and pain syndromes. The
      aim of the present simulation study was to assess the influence of altered
      ligament function on pelvis motion. A finite elements computer model was used.
      The two-leg stance was simulated, with the load of body weight applied via the
      fifth lumbar vertebra and both femora, allowing for nutation of the sacroiliac
      joint. The in-silico kinematics were validated with in-vitro experiments using
      the same scenario of load application following SS and ST transection in six
      human cadavers. Modeling of partial or complete ligament failure caused
      significant increases in pelvis motion. This effect was most pronounced if the SS
      and ST were affected with 164% and 182%, followed by the sacroiliac and
      iliolumbar ligaments with 123% and 147%, and the pubic ligaments with 113% and
      119%, for partial and complete disruption, respectively. Simultaneous ligament
      transection multiplied the effects on pelvis motion by up to 490%. Unilateral
      ligament injury altered the motion at the pelvis contralaterally. The experiments
      presented here provide strong evidence for the stabilizing role of the SS and ST.
      A fortiori, the instability resulting from partial or complete SS and ST injury
      merits consideration in treatment strategies involving these ligaments as
      important stabilizers. Clin. Anat., 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30281853
TI  - Anatomical study of the seminal vesicle system for transurethral seminal
      vesiculoscopy.
AB  - Because of a general lack of knowledge regarding the precise anatomy of the
      seminal vesicle system, efforts to use transurethral seminal vesiculoscopy (TSV)
      are currently constrained. We investigated 26 normal adult male specimens.
      Contrast medium was injected into the seminal vesicle system in 18 specimens and
      the openings of the ejaculatory ducts were examined with an operating microscope.
      India ink was injected into the urethra in four specimens to investigate the
      function of the ejaculatory duct valve. Another four specimens were examined
      histologically to identify the anatomical relationships of the seminal vesicle
      system. We found that the openings of the ejaculatory ducts were covered by the
      ejaculatory duct valve, which could be classified into two types and acted as a
      one-way valve. The apex of the seminal colliculus together with the right and
      left openings of the ejaculatory ducts formed a shape resembling an isosceles
      triangle. This could be used to locate the openings of the ejaculatory ducts
      during TSV. The ejaculatory ducts can be classified into two types according to
      their course. During surgery, efforts must be made to protect the ejaculatory
      duct valve. During inspection or surgery, the second segment and the angles of
      the ejaculatory ducts, particularly in Type Ib and Type II cases, require
      particular attention. Clin. Anat., 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30281854
TI  - Preservation of neural tissue with a formaldehyde-free phenol-based embalming
      protocol.
AB  - The adverse effects formaldehyde fixation has on tissues both gross anatomically
      and histologically are well documented. Consequently, researchers are seeking
      alternative embalming techniques that better preserve in vivo characteristics of
      tissues. Phenol-based embalming is one method that has shown promise in its
      ability to adequately preserve the in vivo qualities of tissues through
      preliminary explorations at the gross anatomical level. The literature on phenol
      based embalming is currently scarce, especially with regard to its effects on
      tissues at the microscopic level. For the current study we aimed to document the
      histologic effects of a formaldehyde-free phenol-based embalming solution on
      neural tissue, with the hope of providing novel insight into the effects of soft
      embalming on tissues at the microscopic level. Cerebral and cerebellar tissue
      obtained from porcine brains was fixed in phenol- and formaldehyde-based
      fixatives; the latter served as a control. Fixed samples were processed for
      histological analysis. The phenol-based embalming solution provided excellent
      preservation of the cerebral and cerebellar tissue morphology. Of note was the
      decrease in separation artifact seen in both tissue types relative to the control
      tissue, as well as anomalous circular artifacts in the white matter. The results
      of this study indicate that the phenol-based embalming solution preserves neural
      tissue at the histological level, perhaps superiorly in many aspects when
      compared to the formaldehyde-fixed samples. Further investigations of both gross
      anatomy and histology are recommended on the basis of these promising new
      findings to determine its potential utilities within research and education.
      Clin. Anat., 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30281855
TI  - Polyamine-independent growth and biofilm formation, and functional
      spermidine/spermine N-acetyltransferases in Staphylococcus aureus and
      Enterococcus faecalis.
AB  - Polyamines such as spermidine and spermine are primordial polycations that are
      ubiquitously present in the three domains of life. We have found that Gram
      positive bacteria Staphylococcus aureus and Enterococcus faecalis have lost
      either all or most polyamine biosynthetic genes, respectively, and are devoid of
      any polyamine when grown in polyamine-free media. In contrast to bacteria such as
      Pseudomonas aeruginosa, Campylobacter jejuni and Agrobacterium tumefaciens, which
      absolutely require polyamines for growth, S. aureus and E. faecalis grow normally
      over multiple subcultures in the absence of polyamines. Furthermore, S. aureus
      and E. faecalis form biofilms normally without polyamines, and exogenous
      polyamines do not stimulate growth or biofilm formation. High levels of external
      polyamines, including norspermidine, eventually inhibit biofilm formation through
      inhibition of planktonic growth. We show that spermidine/spermine N
      acetyltransferase (SSAT) homologues encoded by S. aureus USA300 and E. faecalis
      acetylate spermidine, spermine and norspermidine, that spermine is the more
      preferred substrate, and that E. faecalis SSAT is almost as efficient as human
      SSAT with spermine as substrate. The polyamine auxotrophy, polyamine-independent
      growth and biofilm formation, and presence of functional polyamine N
      acetyltransferases in S. aureus and E. faecalis represent a new paradigm for
      bacterial polyamine biology.

PMID- 30281856
TI  - The microbiome of the "sterile" pustules in palmoplantar pustulosis.
AB  - The skin microbiome influences skin pathophysiology. Palmoplantar pustulosis
      (PPP) is a chronic skin disease characterized by infectious-like pustules on the
      palms and soles. These pustules are thought to be sterile because bacterial
      cultures obtained from the pustules are negative. However, culture methods are
      limited in their ability to identify all bacteria on the skin. We hypothesized
      that the "sterile" pustules of PPP do not lack bacteria, but rather contain a
      microbiome. To test this hypothesis, we identified bacteria in "sterile" pustules
      using non-culture methods. We conducted Sanger and 16S rRNA sequencing using
      primers specific to the V1-V2 region in PPP-pustulovesicles (PVs) (n = 43) and
      pompholyx vesicle fluids (n = 15). Sanger sequencing identified some
      Staphylococcus, Propionibacterium, Streptococcus and Pyrinomonas species in PPP
      PVs but failed to identify any bacteria in most of the pompholyx vesicles. 16S
      rRNA sequencing of PPP-PVs indicated the presence of a microbiome that included
      various phyla, including Firmicutes, Proteobacteria, Actinobacteria and
      Bacteroidetes. At the genus level, smokers had higher levels of Staphylococcus in
      PPP-PVs compared with non-smokers. These results indicate that a microbiome
      exists in "sterile" pustules of PPP and that PPP smokers had higher levels of
      Staphylococcus in pustules. It is therefore necessary to reconsider the
      pathogenesis of PPP from the perspective of the microbiome.

PMID- 30281857
TI  - Comparison of autogenous and allograft bone rings in surgically created vertical
      bone defects around implants in a sheep model.
AB  - OBJECTIVES: The aim of this study was to compare autogenous and allograft bone
      rings in surgically created vertical bone defects. MATERIAL AND METHODS: Four
      male, 1-year-old sheep were used in this study. In each sheep, eight vertical
      bone defects 7 mm in diameter were created using trephine drill in the iliac
      wing. Autogenous and allograft bone rings 5 mm in height and 7 mm in diameter
      were used for vertical augmentation around implants. The study consisted of four
      groups according to the bone ring type and amount of vertical augmentation,
      autogenous 2 mm, allograft 2 mm, autogenous 4 mm, and allograft 4 mm. Two of the
      animals were sacrificed after 4 months, and the remaining two animals were
      sacrificed after 8 months. Undecalcified sections were prepared from harvested
      samples. Histological assessment and histomorphometric analysis were performed.
      RESULTS: Autogenous 2 mm group showed higher values than allograft 2 mm group,
      and autogenous 4 mm group showed higher values than allograft 4 mm group in terms
      of bone area and bone-to-implant contact (BIC) after 4 months. However, allograft
      2 mm group showed higher bone area and BIC values than autogenous 2 mm group
      after 8 months. Also, autogenous 4 mm and allograft 4 mm groups showed comparable
      results after 8 months. Allograft 2 mm and allograft 4 mm groups showed higher
      bone area and BIC values at 8 months compared with 4 months. CONCLUSIONS:
      Allograft bone ring looks promising in augmentation of surgically created
      vertical bone defects around implants after 8 months of healing.

PMID- 30281858
TI  - The frequency architecture of brain and brain body oscillations: an analysis.
AB  - Research on brain oscillations has brought up a picture of coupled oscillators.
      Some of the most important questions that will be analyzed are, how many
      frequencies are there, what are the coupling principles, what their functional
      meaning is, and whether body oscillations follow similar coupling principles. It
      is argued that physiologically, two basic coupling principles govern brain as
      well as body oscillations: (i) amplitude (envelope) modulation between any
      frequencies m and n, where the phase of the slower frequency m modulates the
      envelope of the faster frequency n, and (ii) phase coupling between m and n,
      where the frequency of n is a harmonic multiple of m. An analysis of the center
      frequency of traditional frequency bands and their coupling principles suggest a
      binary hierarchy of frequencies. This principle leads to the foundation of the
      binary hierarchy brain body oscillation theory. Its central hypotheses are that
      the frequencies of body oscillations can be predicted from brain oscillations and
      that brain and body oscillations are aligned to each other. The empirical
      evaluation of the predicted frequencies for body oscillations is discussed on the
      basis of findings for heart rate, heart rate variability, breathing frequencies,
      fluctuations in the BOLD signal, and other body oscillations. The conclusion is
      that brain and many body oscillations can be described by a single system, where
      the cross talk - reflecting communication - within and between brain and body
      oscillations is governed by m : n phase to envelope and phase to phase coupling.

PMID- 30281859
TI  - The transplantation of corneae from cadavers can prevent blindness.
AB  - This Viewpoint describes the process by which corneae are obtained from body
      donors to anatomical institutes for subsequent clinical transplantation. Corneae
      from body donors are extremely valuable in clinical medicine. Clin. Anat., 2018.
      (c) 2018 Wiley Periodicals, Inc.

PMID- 30281860
TI  - Solution-Processable Two-Dimensional In2 Se3 Nanosheets as Efficient Photothermal
      Agents for Elimination of Bacteria.
AB  - Two-dimensional (2D) nanoflakes represent an appealing class of materials for
      optoelectronics applications due to their unique layered structures and excellent
      electronic properties. However, the lack of easy-to-manipulate and effective
      methods for large-scale production of these 2D materials limits their potential
      for applications. Also, few efforts have been made to explore their applications
      in biological fields. This work reports the preparation of large quantities of 2D
      In2 Se3 nanosheets through a solvent exfoliation technique. Transmission electron
      microscopy and atomic force microscopy results show that the In2 Se3 nanosheets
      are obtained with lateral sizes of tens of nanometers to hundreds of nanometers
      and thickness of 2-17 layers. Raman features coupled with the X-ray
      diffractometry results unequivocally confirm the as-prepared In2 Se3 nanosheets
      to be alpha phase. Moreover, these alpha-In2 Se3 nanosheets exhibit an excellent
      near-infrared (NIR) photothermal performance under an 808 nm laser irradiation.
      NIR photo-excitation of the alpha-In2 Se3 nanosheets in the presence of bacteria
      leads to a significant antibacterial effect, suggesting that these nanosheets
      have great potential to be photothermal antibacterial agents. Our work on alpha
      In2 Se3 nanosheets presents an available method for exfoliating 2D layered
      materials, and highlights the potential application in chemical and biological
      fields of alpha-In2 Se3 nanosheets.

PMID- 30281861
TI  - Fundus image classification methods for the detection of glaucoma: A review.
AB  - Glaucoma is a neurodegenerative illness and is considered as a standout amongst
      the most widely recognized reasons for visual impairment. Nerve's degeneration is
      an irretrievable procedure, so the diagnosis of the illness at an early stage is
      an absolute requirement to stay away from lasting loss of vision. Glaucoma
      effected mainly because of increased intraocular pressure, if it is not
      distinguished and looked early, it can result in visual impairment. There are not
      generally evident side effects of glaucoma; thus, patients attempt to get
      treatment just when the seriousness of malady is advanced altogether.
      Determination of glaucoma often comprises of review of the basic crumbling of the
      nerve in conjunction with the examination of visual function capacity. This
      article shows the persistent illustration of glaucoma, its side effects, and the
      potential people inclined to this malady. The essence of this article is on
      different classification methods being utilized and proposed by various
      scientists for the identification of glaucoma. This article audits a few division
      and segmentation methodologies that are exceptionally useful for recognizable
      proof, identification, and diagnosis of glaucoma. The research related to the
      findings and the treatment is likewise evaluated in this article.

PMID- 30281862
TI  - Independent homoploid hybrid speciation events in the Macaronesian endemic genus
      Argyranthemum.
AB  - Well-characterized examples of homoploid hybrid speciation (HHS) are rare in
      nature, yet they offer the potential to study a number of evolutionary processes.
      In this study, we investigate putative homoploid hybrid species in the genus
      Argyranthemum (Asteraceae), a group of plants endemic to the Macaronesian
      archipelagos of the North Atlantic Ocean. We specifically address a number of
      knowledge gaps surrounding the origin(s) of A. sundingii and A. lemsii, which are
      thought to be derived from the same parental cross. Comparisons of leaf
      morphology suggest that A. sundingii and A. lemsii are distinct from their
      parental progenitors and distinguishable from each other based on leaf area.
      Ecological niche modelling (ENM) demonstrated that the homoploid hybrid species
      occupy novel habitats that are intermediate relative to the parental species.
      Nuclear simple sequence repeat markers (SSRs) and single nucleotide polymorphism
      (SNP) data indicate that the homoploid hybrid species are distinct from the
      parental taxa, while population-level sampling of chloroplast SSRs and
      approximate Bayesian computation show that A. sundingii and A. lemsii are
      independently derived from the same parental cross. As such, Argyranthemum
      represents an example of independent homoploid hybrid speciation events with
      evidence of divergence in leaf morphology and adaptation to novel intermediate
      habitats. On oceanic islands, which are often typified by steep ecological
      gradients and inhabited by recently derived species with weak reproductive
      barriers, multiple HHS events from the same parental cross are not only possible
      but also likely to have played a more important role in oceanic island radiations
      than we currently think.

PMID- 30281864
TI  - Digital enhancement of dental enamel microstructure images from intact teeth.
AB  - Dental enamel is formed by rod-like structures, the enamel prisms. Groups of
      prisms are packed together in successive horizontal layers of alternating
      directions, known as Hunter-Schreger bands (HSBs). HSBs are the major
      microstructural characteristic of mammalian enamel. The pattern of HSBs can vary
      among mammalian species and this variability may provide relevant information
      regarding the species life history and taxon identification. In human HSBs can be
      used as a biometric-based parameter for personal identification in automated
      systems. The analysis of HSBs has been hampered by technical difficulties. The
      low contrast between light and dark bands and variations in light intensity may
      hinder the observation of HSBs in digital images. This article describes a simple
      and efficient computational procedure that greatly enhances the contrast and
      minimizes the differences in the intensity of illumination in HSBs images. Its
      use can significantly increase the quality and the number of HSBs that can be
      recorded in intact teeth.

PMID- 30281863
TI  - Cortical bone material strength index and bone microarchitecture in
      postmenopausal women with atypical femoral fractures.
AB  - Atypical femoral fractures are rare fractures that occur in the subtrochanteric
      or diaphyseal region of the femur with minimal or no trauma. Though the
      association of atypical femoral fractures (AFFs) and bisphosphonate (BP) use is a
      growing concern in the management of osteoporosis, currently there is little
      knowledge about which patients may be at risk for an atypical femoral fracture.
      Given that these fractures initiate in the femoral cortex, we aimed to determine
      whether cortical bone tissue properties (bone material strength index; BMSi), as
      measured by in vivo impact microindentation, are altered in atypical fracture
      patients. We also aimed to identify factors associated with the BMSi
      measurements. We enrolled postmenopausal women with recent AFFs (n = 15) or hip
      fractures (Hip Fxs; n = 20), long-term (>5 years) BP users (n = 30), and
      treatment naive controls (n = 88). We measured total hip and femoral neck BMD by
      DXA, cortical bone microstructure at the distal tibia by HR-pQCT, and BMSi at the
      midtibia by impact microindentation. BMSi values were similar in all groups, with
      no effects of long-term BP use or lower values in patients with AFFs or Hip Fxs,
      even after multivariable adjustment. BMSi measurements were independent of age,
      femoral BMD, duration of BP treatment, vitamin D level, and cortical bone
      microstructure, including cortical porosity and cortical tissue mineral density.
      In conclusion, impact microindentation values are not negatively affected by long
      term BP use and do not appear to discriminate individuals who suffer AFFs. Thus,
      our results do not support clinical use of impact microindentation to identify
      those at risk for AFFs. This remains to be verified in larger studies. (c) 2018
      American Society for Bone and Mineral Research.

PMID- 30281865
TI  - Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in
      athletic performance, ageing, and disease.
AB  - A common null polymorphism in the ACTN3 gene (rs1815739:C>T) results in
      replacement of an arginine (R) with a premature stop codon (X) at amino acid 577
      in the fast muscle protein alpha-actinin-3. The ACTN3 p.Arg577Ter allele (aka
      p.R577* or R577X) has undergone positive selection, with an increase in the X
      allele frequency as modern humans migrated out of Africa into the colder, less
      species-rich Eurasian climates suggesting that the absence of alpha-actinin-3 may
      be beneficial in these conditions. Approximately 1.5 billion people worldwide are
      completely deficient in alpha-actinin-3. While the absence of alpha-actinin-3
      influences skeletal muscle function and metabolism this does not result in overt
      muscle disease. alpha-Actinin-3 deficiency (ACTN3 XX genotype) is constantly
      underrepresented in sprint/power performance athletes. However, recent findings
      from our group and others suggest that the ACTN3 R577X genotype plays a role
      beyond athletic performance with effects observed in ageing, bone health, and
      inherited muscle disorders such as McArdle disease and Duchenne muscle dystrophy.
      In this review, we provide an update on the current knowledge regarding the
      influence of ACTN3 R577X on skeletal muscle function and its potential biological
      and clinical implications. We also outline future research directions to explore
      the role of alpha-actinin-3 in healthy and diseased populations.

PMID- 30281866
TI  - Efficacy of house dust mite sublingual tablet in the treatment of allergic
      rhinoconjunctivitis: A randomized trial in a pediatric population.
AB  - BACKGROUND: The efficacy and safety of 300 index of reactivity (IR) tablets of
      house dust mite (HDM) allergen extracts in Japanese pediatric (5-16 years old)
      patients with allergic rhinitis (AR) were assessed in a double-blind, randomized,
      placebo-controlled study (JAPIC CTI-152981). METHODS: Patients were randomized
      1:1 to HDM sublingual tablets or placebo once daily for 52 weeks. The primary end
      point was average adjusted symptom score (AASS; average of daily Rhinitis Total
      Symptom Scores, comprising sneezing, rhinorrhea, nasal congestion, and nasal
      pruritus, adjusted for rescue medication use), analyzed during Weeks 48-52 (mixed
      effects model for repeated measures). RESULTS: Of 438 patients randomized, 403
      (92%; 193 active, 210 placebo) completed the study. AASS (least-squares [LS] mean
      [SE]) during Weeks 48-52 was significantly (P = 0.0005) lower in the active group
      compared with placebo (6.32 [0.20] vs 7.27 [0.19]; relative LS mean difference, 
      13%). Immunological responses (IgE and IgG4 antibodies specific to antigens of
      two HDM species) were significantly greater in the active group compared with
      placebo (P < 0.0001). Almost all patients experienced mild or moderate adverse
      events (AEs). The most common treatment-related AEs were oral pruritus, mouth
      edema, throat irritation, and ear pruritus. One patient experienced serious
      pseudocroup (subglottic laryngitis) that recovered. There were no deaths or
      anaphylaxis requiring the use of injectable adrenaline. CONCLUSIONS: The HDM
      tablet significantly improved symptoms of HDM-induced perennial AR and was
      associated with a significant immunological response. The safety profile in
      pediatric patients was consistent with that in adults, with no new safety
      concerns.

PMID- 30281867
TI  - New Species of Closely Related Endosymbiotic Dinoflagellates in the Greater
      Caribbean have Niches Corresponding to Host Coral Phylogeny.
AB  - Symbiotic dinoflagellates in the genus Breviolum (formerly Symbiodinium Clade B)
      dominate coral communities in shallow waters across the Greater Caribbean. While
      some formally described species exist, mounting genetic, and ecological evidence
      indicate that numerous more comprise this genus, many of which are closely
      related. To test this, colonies of common reef-building corals were sampled
      across a large geographical range. Phylogenetic and population genetic markers
      then used to examine evolutionary divergence and delineate boundaries of genetic
      recombination. Three new candidate species were distinguished by fixed
      differences in nucleotide sequences from nuclear and chloroplast DNA. Population
      connectivity was evident within each lineage over thousands of kilometers,
      however, substantial genetic structure persisted between lineages co-occurring
      within sampling locations, signifying reproductive isolation. While
      geographically widespread with overlapping distributions, each species is
      ecologically distinct, exhibiting specific mutualisms with phylogenetically
      distinct coral hosts. Moreover, significant differences in mean cell sizes
      provide some morphological evidence substantiating formal species distinctions.
      In providing evidence that satisfies the biological, phylogenetic, ecological,
      and morphological species concepts, we classify and formally name Breviolum
      faviinorum n. sp., primarily associated with Caribbean corals belonging to the
      Caribbean subfamily Faviinae; B. meandrinium n. sp., associated with corals
      belonging to the family Meandrinidae; and B. dendrogyrum n. sp., a symbiont
      harbored exclusively by the threatened coral Dendrogyra cylindrus. These findings
      support the primary importance of niche diversification (i.e. host habitat) in
      the speciation of symbiotic dinoflagellates.

PMID- 30281868
TI  - Pain, balance, grip strength and gait parameters of older adults with and without
      post-chikungunya chronic arthralgia.
AB  - OBJECTIVE: To compare the levels of pain, grip strength, balance and gait in
      older adults with and without post-Chikungunya chronic arthralgia (PCCA).
      METHODS: Sixty-two older adults, 30 with and 32 without PCCA participated in the
      study. Pain level was assessed using a Visual Analogue Scale (VAS). Gait during a
      10-m walk was assessed using inertial sensors. Semi-static balance was assessed
      during an eyes-closed bipedal balance test on a force platform, and grip strength
      was assessed using a hand dynamometer. RESULTS: Participants with PCCA presented
      severe levels of pain (VAS > 7.5), poorer balance, lower grip strength, walked
      slower, with lower cadence and stride length and higher stride time and stride
      length variability than participants without PCCA (P < 0.001 for all variables).
      CONCLUSIONS: Older adults with PCCA had high levels of pain, impaired balance and
      gait and lower grip strength compared to older adults without PCCA.

PMID- 30281869
TI  - Regulation of LRG1 expression by RNA-binding protein Puf5 in the budding yeast
      cell wall integrity pathway.
AB  - The PUF RNA-binding protein Puf5 is involved in regulation of the cell wall
      integrity (CWI) pathway in yeast. Puf5 negatively regulates expression of LRG1
      mRNA, encoding for a GTPase-activating protein for Rho1 small GTPase. Here, we
      further analyzed the effect of Puf5 on LRG1 expression, together with Ccr4 and
      Pop2 deadenylases, Dhh1 decapping activator, and other PUF proteins. We found
      that the growth defect of puf5? mutant was enhanced by ccr4? mutation, which was
      partially suppressed by LRG1 deletion. Consistently, Lrg1 protein level was much
      more up-regulated in ccr4Delta puf5Delta double mutant than in each single
      mutant. Interestingly, LRG1 poly(A) tail length was longer in ccr4? mutant but
      not in puf5? mutant. Thus, Puf5 regulates LRG1 expression independently from
      Ccr4, although Puf5 recruits the Ccr4-Not deadenylase complex for mRNA
      destabilization. Unexpectedly, puf6Delta mutation suppressed the growth defect
      caused by ccr4Delta puf5? mutation. Loss of Rpl43a and Rpl43b ribosomal proteins,
      the previously identified Puf6 interactors, also suppressed the growth defect of
      ccr4Delta puf5Delta mutant. Our results suggest that Puf5 functions in the CWI
      pathway by regulating LRG1 expression in a deadenylase-independent manner, and
      that Puf6 is involved in the Ccr4- and Puf5-mediated regulation of cell growth
      through association with Rpl43.

PMID- 30281870
TI  - A Subset of Paracrine Factors as Efficient Biomarkers for Predicting Vascular
      Regenerative Efficacy of Mesenchymal Stromal/Stem Cells.
AB  - Mesenchymal stromal/stem cells (MSCs) have been developed as a promising source
      for cell-based therapies of ischemic disease. However, there are some hurdles in
      their clinical application such as poor cell engraftment and inconsistent stem
      cell potency. In this study, we sought to find biomarkers for predicting potency
      of MSCs for proangiogenic therapy to improve their beneficial effects. Large
      variations were observed in proangiogenic factor secretion profiles of
      conditioned media derived from nine different donor-derived Wharton's jelly (WJ)
      derived MSCs and 8 factors among 55 angiogenesis-related factors were secreted at
      considerable levels. Two distinct WJ-MSCs that had the lowest or the highest
      secretion of these eight factors showed corresponding proangiogenic activities in
      in vitro angiogenesis assays. When four additional different donor-derived WJ
      MSCs were further examined, proangiogenic activities in migration and tube
      formation of endothelial cells and in in vivo Matrigel plug assay were highly
      consistent with secretion levels of four major factors (angiogenin, interleukin
      8, monocyte chemoattractant protein-1, and vascular endothelial growth factor).
      Such correlation was also observed in vascular regenerative effect in a mouse
      hind limb ischemia model. Blocking of these four factors by neutralizing
      antibodies or knockdown of them by siRNA treatment resulted in significant
      inhibition of proangiogenic activities of not only WJ-MSCs, but also bone marrow
      derived MSCs. These results suggest that these four factors may represent
      efficient biomarkers for predicting vascular regenerative efficacy of MSCs. Stem
      Cells 2018.

PMID- 30281873
TI  - Response to Commentary by Russo, Beresford, and O'Hagan To Happell, Brenda, &
      Scholz, Brett (2018). Doing what we can, but knowing our place: Being an ally to
      promote consumer leadership in mental health. International Journal of Mental
      Health Nursing, 27(1), 440-447.

PMID- 30281871
TI  - Langerhans cell histiocytosis in adults: Advances in pathophysiology and
      treatment.
AB  - Langerhans cell histiocytosis (LCH) is a rare systemic disorder characterized by
      the accumulation of CD1a+/Langerin+ LCH cells and wide-ranging organ involvement.
      Langerhans cell histiocytosis was formerly referred to as histiocytosis X, until
      it was renamed in 1987. Langerhans cell histiocytosis beta was named for its
      morphological similarity to skin Langerhans cells. Studies have shown that LCH
      cells originate from myeloid dendritic cells rather than skin Langerhans cells.
      There has been significant debate regarding whether LCH should be defined as an
      immune disorder or a neoplasm. A breakthrough in understanding the pathogenesis
      of LCH occurred in 2010 when a gain-of-function mutation in BRAF (V600E) was
      identified in more than half of LCH patient samples. Studies have since reported
      that 100% of LCH cases show ERK phosphorylation, indicating that LCH is likely to
      be a clonally expanding myeloid neoplasm. Langerhans cell histiocytosis is now
      defined as an inflammatory myeloid neoplasm in the revised 2016 Histiocyte
      Society classification. Randomized trials and novel approaches have led to
      improved outcomes for pediatric patients, but no well-defined treatments for
      adult patients have been developed to date. Although LCH is not fatal in all
      cases, delayed diagnosis or treatment can result in serious impairment of organ
      function and decreased quality of life. This study summarizes recent advances in
      the pathophysiology and treatment of adult LCH, to raise awareness of this
      "orphan disease".

PMID- 30281872
TI  - Functional intronic variant of SLC5A10 affects DRG2 expression and survival
      outcomes of early-stage non-small-cell lung cancer.
AB  - RegulomeDB is a new tool that can predict the regulatory function of genetic
      variants. We applied RegulomeDB in selecting putative functional variants and
      evaluated the relationship between these variants and survival outcomes of
      surgically resected non-small-cell lung cancer. Among the 244 variants studied,
      14 were associated with overall survival (P < 0.05) in the discovery cohort and
      one variant (rs2257609 C>T) was replicated in the validation cohort. In the
      combined analysis, rs2257609 C>T was significantly associated with worse overall
      and disease-free survival under a dominant model (P = 2 * 10-5 and P = 0.001,
      respectively). rs2257609 is located in the SLC5A10 intron, but RegulomeDB
      predicted that this variant affected DRG2, not SLC5A10 expression. The expression
      level of SLC5A10 was not different with the rs2257609 genotype. However, DRG2
      expression was different according to the rs2257609 genotype (Ptrend   = 0.03)
      and was significantly higher in tumor than in non-malignant lung tissues (P = 1 *
      10-5 ). Luciferase assay also showed higher promoter activity of DRG2 in samples
      with the rs2257609 T allele (P < 0.0001). rs2257609 C>T affected DRG2 expression
      and, thus, influenced the prognosis of early-stage non-small-cell lung cancer.
      This study was approved by the Institutional Review Broad of Kyungpook National
      University of Hospital (Approval No. KNUMC 2014-04-210-003).

PMID- 30281876
TI  - Time trends in use of the CHADS2 and CHA2 DS2 VASc scores, and the geographical
      and specialty uptake of these scores from a popular online clinical decision tool
      and medical reference.
AB  - BACKGROUND: The impact of the utilisation of such e-health approaches, including
      mHealth (use of mobile phones and other wireless technology in the delivery of
      medical care) assessments of health parameters, or the use of decision aids and
      online risk calculators over time have not been previously described. The
      objective of this analysis is to assess the time trends in use of the CHADS2 and
      CHA2 DS2 VASc scores in e-health, and the geographical and specialty uptake of
      these scores, using data gleaned from a popular online clinical decision tool and
      medical reference, MDCalc. We hypothesised that the change in use of the scores
      would reflect the changes in guidelines and trends in clinical practice. RESULTS:
      The CHA2 DS2 VASc score was the 20th most popular calculator in 2012, rising to
      the second most popular calculator in 2018; the CHADS2 score showed the converse,
      dropping from no. 3 to no. 22. Use of the CHA2 DS2 VASc scores particularly
      increased in the United States, Canada and Australia over time while the United
      Kingdom experienced a greater traffic share in 2015. The majority users of the
      CHADS2 and CHA2 DS2 VASc scores were primary care physicians, with cardiologists
      being in the minority; the proportion of cardiologists was greater outside USA,
      compared to within USA. CONCLUSION: Over time, use of the CHA2 DS2 VASc score
      increased, while use of the CHADS2 score decreased. The change in uptake could
      partly be related to introduction of guidelines recommending the use of the CHA2
      DS2 VASc score for stroke risk stratification.

PMID- 30281877
TI  - Patient-derived organoids: New co-clinical model to predict treatment response in
      cancer?

PMID- 30281874
TI  - Genome-wide association study identifies gastric cancer susceptibility loci at
      12q24.11-12 and 20q11.21.
AB  - Gastric cancer is the third leading cause of cancer mortality in Japan and
      worldwide. Although previous studies identify various genetic variations
      associated with gastric cancer, host genetic factors are largely unidentified. To
      identify novel gastric cancer loci in the Japanese population, herein, we carried
      out a large-scale genome-wide association study using 6171 cases and 27 178
      controls followed by three replication analyses. Analysis using a total of 11 507
      cases and 38 904 controls identified two novel loci on 12q24.11-12 (rs6490061, P
      = 3.20 * 10-8 with an odds ratio [OR] of 0.905) and 20q11.21 (rs2376549, P = 8.11
      * 10-10 with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene,
      and its expression was suppressed by Helicobacter pylori infection. rs2376549 is
      included within the gene cluster of DEFB families that encode antibacterial
      peptides. We also found a significant association of rs7849280 in the ABO gene
      locus on 9q34.2 (P = 2.64 * 10-13 with an OR of 1.148). CUX2 and ABO expression
      in gastric mucosal tissues was significantly associated with rs6490061 and
      rs7849280 (P = 0.0153 and 8.00 * 10-11 ), respectively. Our findings show the
      crucial roles of genetic variations in the pathogenesis of gastric cancer.

PMID- 30281875
TI  - Phase II clinical trial of S-1 plus nanoparticle albumin-bound paclitaxel in
      untreated patients with metastatic gastric cancer.
AB  - The present study is the first phase II clinical trial aimed to evaluate the
      efficacy and safety of S-1 plus nanoparticle albumin-bound paclitaxel (Nab-PTX)
      as first-line chemotherapy for advanced gastric cancer (AGC). Previously
      untreated patients with metastatic gastric adenocarcinoma received S-1 in oral
      doses of 40 mg (BSA <1.25 m2 ), 50 mg (1.25 <= BSA < 1.50 m2 ) and 60 mg (BSA
      >=1.50 m2 ) b.i.d. on days 1-14 in combination with Nab-PTX (120 mg/m2 , on days
      1 and 8) for each 21-day cycle. Primary endpoint was progression-free survival
      (PFS), and secondary endpoints were overall response rate (ORR), overall survival
      (OS), disease control rate (DCR), and toxicity. A total of 73 gastric cancer
      patients with metastatic and measurable lesions were enrolled in the first-line
      setting. Median PFS and OS were 9.63 months and 14.60 months, respectively. Four
      (5.5%) patients had complete responses, 39 (53.4%) had partial responses (PRs),
      21 (28.8%) had stable disease, four (5.5%) progressed and five (6.8%) were not
      evaluable. ORR and DCR were 58.9% and 87.7%, respectively. Most toxicities were
      mild, and no treatment-related deaths occurred. Grade 3 to 4 toxicities occurred
      in 22 patients (30.1%) as follows: leukopenia (13.7%), neutropenia (12.3%),
      anemia (5.5%), thrombocytopenia (1.4%), diarrhea (6.8%), vomiting (2.7%),
      stomatitis (1.4%), peripheral neuropathy (1.4%), and hand-foot syndrome (1.4%).
      Seven patients achieved good responses and underwent gastrectomy plus
      metastasectomy. Thirty (41.1%) patients had S-1 maintenance with a median of four
      cycles. S-1 plus Nab-PTX is an efficient and safe regimen as first-line treatment
      for patients with AGC.

PMID- 30281879
TI  - Heart transplantation for infective endocarditis: Viable option for a limited
      few?
AB  - Active infection in the recipient is considered a relative contraindication for
      solid organ transplantation. However, heart transplantation (HT) can be curative
      in patients with ventricular assist device infections. For patients with
      infective endocarditis (IE), valve replacement is part of the management strategy
      based on emergent, acute, or elective indications. HT has been utilized as an
      uncommon and sporadic treatment option for carefully selected patients with
      refractory or recurrent IE after all other surgical treatment options have been
      exhausted or are not feasible. Herein, we review 19 published cases of IE in whom
      HT was undertaken in the setting of ongoing active infection with reported good
      outcomes. We attempt to propose general criteria for HT in the setting of IE and
      discuss challenges and hurdles that clinicians might encounter when considering
      HT for active IE in the absence of robust data or clearly defined criteria.

PMID- 30281880
TI  - Calcium-regulated mitochondrial ATP-Mg/Pi carriers evolved from a fusion of an EF
      hand regulatory domain with a mitochondrial ADP/ATP carrier-like domain.
AB  - The mitochondrial ATP-Mg/Pi carrier is responsible for the calcium-dependent
      regulation of adenosine nucleotide concentrations in the mitochondrial matrix,
      which allows mitochondria to respond to changing energy requirements of the cell.
      The carrier is expressed in mitochondria of fungi, plants and animals and belongs
      to the family of mitochondrial carriers. The carrier is unusual as it consists of
      three separate domains: (i) an N-terminal regulatory domain with four calcium
      binding EF-hands similar to calmodulin, (ii) a loop domain containing an
      amphipathic alpha-helix and (iii) a mitochondrial carrier domain related to the
      mitochondrial ADP/ATP carrier. This striking example of three domains coming
      together from different origins to provide new functions represents an
      interesting quirk of evolution. In this review, we outline how the carrier was
      identified and how its physiological role was established with a focus on human
      isoforms. We exploit the sequence and structural information of the domains to
      explore the similarities and differences to their closest counterparts;
      mitochondrial ADP/ATP carriers and proteins with four EF-hands. We discuss how
      their combined function has led to a mechanism for calcium-regulated transport of
      adenosine nucleotides. Finally, we compare the ATP-Mg/Pi carrier with the
      mitochondrial aspartate/glutamate carrier, the only other mitochondrial carrier
      regulated by calcium, and we will argue that they have arisen by convergent
      rather than divergent evolution. (c) 2018 The Authors. IUBMB Life published by
      Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and
      Molecular Biology, 70(12):1222-1232, 2018.

PMID- 30281881
TI  - w-type ions formed by Electron Transfer Dissociation of Cys-containing peptides
      investigated by infrared ion spectroscopy.
AB  - In mass spectrometry-based peptide sequencing, Electron Transfer Dissociation
      (ETD) and Electron Capture Dissociation (ECD) have become well established
      fragmentation methods complementary to collision-induced dissociation (CID). The
      dominant fragmentation pathways during ETD and ECD primarily involve the
      formation of c- and z* -type ions by cleavage of the peptide backbone at the N -
      Calpha bond, although neutral losses from amino acid side chains have also been
      observed. Residue-specific neutral side chain losses provide useful information
      when conducting database searching and de novo sequencing. Here we use a
      combination of infrared ion spectroscopy and quantum-chemical calculations to
      assign the structures of two ETD-generated w-type fragment ions. These ions are
      spontaneously formed from ETD-generated z* -type fragments by neutral loss of 33
      Da in peptides containing a cysteine residue. Analysis of the infrared ion
      spectra confirms that these z* -ions expel a thiol radical (SH* ) and that a
      vinyl C=C group is formed at the cleavage site. z* -type fragments containing a
      Cys residue but not at the cleavage site do not spontaneously expel a thiol
      radical, but only upon additional collisional activation after ETD.

PMID- 30281878
TI  - p53-inducible gene 3 promotes cell migration and invasion by activating the
      FAK/Src pathway in lung adenocarcinoma.
AB  - The p53-inducible gene 3 (PIG3) is one of the p53-induced genes at the onset of
      apoptosis, which plays an important role in cell apoptosis and DNA damage
      response. Our previous study reported an oncogenic role of PIG3 associated with
      tumor progression and metastasis in non-small cell lung cancer (NSCLC). In this
      study, we further analyzed PIG3 mRNA expression in 504 lung adenocarcinoma (LUAD)
      and 501 lung squamous cell carcinoma (LUSC) tissues from The Cancer Genome Atlas
      database and we found that PIG3 expression was significantly higher in LUAD with
      lymph node metastasis than those without, while no difference was observed
      between samples with and without lymph node metastasis in LUSC. Gain and loss of
      function experiments were performed to confirm the metastatic role of PIG3 in
      vitro and to explore the mechanism involved in its oncogenic role in NSCLC
      metastasis. The results showed that PIG3 knockdown significantly inhibited the
      migration and invasion ability of NSCLC cells, and decreased paxillin, phospho
      focal adhesion kinase (FAK) and phospho-Src kinase expression, while its
      overexpression resulted in the opposite effects. Blocking FAK with its inhibitor
      reverses PIG3 overexpression-induced cell motility in NSCLC cells, indicating
      that PIG3 increased cell metastasis through the FAK/Src/paxillin pathway.
      Furthermore, PIG3 silencing sensitized NSCLC cells to FAK inhibitor. In
      conclusion, our data revealed a role for PIG3 in inducing LUAD metastasis, and
      its role as a new FAK regulator, suggesting that it could be considered as a
      novel prognostic biomarker or therapeutic target in the treatment of LUAD
      metastasis.

PMID- 30281882
TI  - Effectiveness of interventions for unstable patients on antiretroviral therapy in
      South Africa: results of a cluster-randomised evaluation.
AB  - BACKGROUND: As loss from HIV care is an ongoing challenge globally, interventions
      are needed for patients who don't achieve or maintain ART stability. The 2015
      South African National Adherence Guidelines (AGL) for Chronic Diseases include
      two interventions targeted at unstable patients: early tracing of patients who
      miss visits (TRIC) and enhanced adherence counselling (EAC). METHODS: As part of
      a cluster-randomised evaluation at 12 intervention and 12 control clinics in four
      provinces, intervention sites implemented the AGL interventions, while control
      sites retained standard care. We report on outcomes of EAC for patients with an
      elevated viral load (>400 copies/ml) and for TRIC patients who missed a visit by
      >5 days. We estimated risk differences (RD) of 3 and 12-month viral resuppression
      (<400 copies/ml) and 12-month retention with cluster adjustment using generalised
      estimating equations and controlled for imbalances using difference-in
      differences compared to all eligible in 2015, prior to intervention roll-out.
      RESULTS: For EAC, we had 358 intervention and 505 control site patients (61%
      female, median ART initiation CD4 count 154 cells/MUl). We found no difference
      between arms in 3-month resuppression (RD: -1.7%; 95%CI: -4.3% to 0.9%), but <20%
      of patients had a repeat viral load within 3 months (19.8% intervention, 13.5%
      control). Including the entire clinic population eligible for EAC with a repeat
      viral load at all evaluation sites (n = 934), intervention sites showed a small
      increase in 3-month resuppression (28% vs. 25%, RD 3.0%; 95%CI: -2.7% to 8.8%).
      Adjusting for baseline differences increased the RD to 8.1% (95% CI: -0.1% to
      17.2%). However, we found no differences in 12-month suppression (RD: 1.5%; 95%
      CI: -14.1% to 17.1% but suppression was low overall at 40%) or retention (RD:
      2.8%; 95% CI: -7.5% to 13.2%). For TRIC, we enrolled 155 at intervention sites
      and 248 at control sites (44% >40 years, 67% female, median CD4 count 212
      cells/MUl). We found no difference between groups in return to care by 12 months
      (RD: -6.8%; 95% CI: -17.7% to 4.8%). During the study period, control sites
      continued to use tracing within standard care, however, potentially masking
      intervention effects. CONCLUSIONS: Enhanced adherence counselling showed no
      benefit over 12 months. Implementation of the tracing intervention under the new
      guidelines was similar to the standard of care. Interventions that aim to return
      unstable patients to care should incorporate active monitoring to determine if
      the interventions are effective.

PMID- 30281883
TI  - Prostate cancer mortality rates in Peru and its geographical regions.
AB  - OBJECTIVE: To evaluate the mortality rates for prostate cancer according to
      geographical areas in Peru between 2005 and 2014. MATERIALS AND METHODS:
      Information was extracted from the Deceased Registry of the Peruvian Ministry of
      Health. We analysed age-standardised mortality rates (world population) per 100
      000 men. Spatial autocorrelation was determined according to the Moran Index. In
      addition, we used Cluster Map to explore relations between regions. RESULTS:
      Mortality rates increased from 20.9 (2005-2009) to 24.1 (2010-2014) per 100 000
      men, an increase of 15.2%. According to regions, during the period 2010-2014, the
      coast had the highest mortality rate (28.9 per 100 000), whilst the rainforest
      had the lowest (7.43 per 100 000). In addition, there was an increase in
      mortality in the coast and a decline in the rainforest over the period 2005-2014.
      The provinces with the highest mortality were Piura, Lambayeque, La Libertad,
      Callao, Lima, Ica, and Arequipa. Moreover, these provinces (except Arequipa)
      showed increasing trends during the years under study. The provinces with the
      lowest observed prostate cancer mortality rates were Loreto, Ucayali, and Madre
      de Dios. This study showed positive spatial autocorrelation (Moran's I: 0.30, P =
      0.01). CONCLUSION: Mortality rates from prostate cancer in Peru continue to
      increase. These rates are higher in the coastal region compared to those in the
      highlands or rainforest.

PMID- 30281884
TI  - Consensus-based Criterion Standard for the Identification of Pediatric Patients
      Who Need Emergency Medical Services Transport to a Hospital with Higher-level
      Pediatric Resources.
AB  - BACKGROUND: Emergency medical services (EMS) providers must be able to identify
      the most appropriate destination facility when treating children with potentially
      severe medical illnesses. Currently, no validated tool exists to assist EMS
      providers in identifying children who need transport to a hospital with higher
      level pediatric care. For such a tool to be developed, a criterion standard needs
      to be defined that identifies children who received higher-level pediatric
      medical care. OBJECTIVE: The objective was to develop a consensus-based criterion
      standard for children with a medical complaint who need a hospital with higher
      level pediatric resources. METHODS: Eleven local and national experts in EMS,
      emergency medicine (EM), and pediatric EM were recruited. Initial discussions
      identified themes for potential criteria. These themes were used to develop
      specific criteria that were included in a modified Delphi survey, which was
      electronically delivered. The criteria were refined iteratively based on
      participant responses. To be included, a criterion required at least 80%
      agreement among participants. If an item had less than 50% agreement, it was
      removed. A criterion with 50% to 79% agreement was modified based on participant
      suggestions and included on the next survey, along with any new suggested
      criteria. Voting continued until no new criteria were suggested and all criteria
      received at least 80% agreement. RESULTS: All 11 recruited experts participated
      in all seven voting rounds. After the seventh vote, there was agreement on each
      item and no new criteria were suggested. The recommended criterion standard
      included 13 items that apply to patients 14 years old or younger. They included
      IV antibiotics for suspicion of sepsis or a seizure treated with two different
      classes of anticonvulsive medications within 2 hours, airway management, blood
      product administration, cardiopulmonary resuscitation, electrical therapy,
      administration of specific IV/IO drugs or respiratory assistance within 4 hours,
      interventional radiology or surgery within 6 hours, intensive care unit
      admission, specific comorbid conditions with two or more abnormal vital signs,
      and technology-assisted children seen for device malfunction. CONCLUSION: We
      developed a 13-item consensus-based criterion standard definition for identifying
      children with medical complaints who need the resources of a hospital equipped to
      provide higher-level pediatric services. This criterion standard will allow us to
      create a tool to improve pediatric patient care by assisting EMS providers in
      identifying the most appropriate destination facility for ill children.

PMID- 30281885
TI  - CdSe/CdS Dot-in-Rods Nanocrystals Fast Blinking Dynamics.
AB  - Analyzing the autocorrelation function of the fluorescence intensity, we
      demonstrate that these nanoemitters are characterized by a short value of the
      mean duration of bright periods (ten to a few hundreds of microseconds). The
      comparison of the results obtained for samples with different geometries shows
      that not only the shell thickness is crucial but also the shape of the dot-in
      rods. Increasing the shell aspect ratio results in shorter bright periods
      suggesting that surface traps impact the stability of the fluorescence intensity.

PMID- 30281886
TI  - Association between lower urinary tract symptoms and cardiovascular risk scores
      in ostensibly healthy women.
AB  - OBJECTIVES: To investigate the association between lower urinary tract symptoms
      (LUTS) and cardiovascular disease (CVD) risk in women, as severe LUTS are known
      to be associated with CVD risk in men but few studies have focused on this issue
      in women. SUBJECTS AND METHODS: A total of 1014 ostensibly healthy women, who
      participated in a voluntary health check in a health promotion centre from
      November 2013 to October 2015, were enrolled. LUTS were assessed using the
      International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score
      (OABSS). CVD risk scores were calculated using the Framingham risk score and the
      American College of Cardiology/American Heart Association Atherosclerotic
      Cardiovascular Disease (ASCVD) score. Correlation, partial correlation, and
      multiple logistic regression analyses were conducted. RESULTS: The mean age and
      body mass index (BMI) of the women were 51 years and 22.6 kg/m2 , respectively.
      The ASCVD score showed significant positive correlations with IPSS items Question
      2 (Q2), Q3, Q5, and Q7 (all P < 0.05), total IPSS (P = 0.001), IPSS storage (P =
      0.006) and IPSS voiding symptoms scores (P = 0.001) based on partial correlation
      analysis after adjustment for BMI. For the OABSS, the ASCVD score showed
      significant positive correlations with OABSS items Q2, Q3, and Q4 (P < 0.001, P =
      0.017, and P < 0.001, respectively) and total OABSS (P < 0.001). Multiple
      logistic regression analysis showed that the moderate-severe risk groups of the
      OABSS and IPSS were associated with the ASCVD risk score in adjusted models (P <
      0.001) compared to the none-mild OABSS and mild IPSS groups. After adjustment for
      age and BMI, IPSS storage score was significantly related with the ASCVD risk
      score (B = 0.855, P = 0.016) CONCLUSIONS: LUTS, especially storage symptoms,
      might be risk factors for predicting future CVD risk in women. Further
      prospective or cohort studies are needed to validate this possibility.

PMID- 30281887
TI  - DNA repair defects in prostate cancer: impact for screening, prognostication and
      treatment.
AB  - Failure of effective DNA damage repair is a hallmark of cancer, but was
      previously underappreciated as a driver of aggressive prostate cancer. However,
      recent international sequencing efforts have revealed that both germline and
      somatic alterations within the homologous recombination and mismatch repair
      pathways are relatively common in lethal metastatic disease. BRCA2 gene
      alterations are particularly prevalent and are linked to poor prognosis as well
      as poor responses to systemic therapy for castration-resistant prostate cancer,
      although there is conflicting support for the latter. Defective DNA repair
      contributes to tumour heterogeneity, evolution and progression, but there are
      high hopes that management of this aggressive subset will be transformed by
      biomarker-driven use of poly-ADP ribose polymerase (PARP) inhibitors and platinum
      based chemotherapy. In this review, we detail the relationship between DNA repair
      defects and prostate cancer, highlighting the prevalence of mutations in key
      genes and their controversial association with clinical outcomes.

PMID- 30281888
TI  - Sphingosine-1-phosphate protects against brain microvascular endothelial
      junctional protein disorganization and barrier dysfunction caused by alcohol.
AB  - OBJECTIVE: S1P has known endothelial barrier-protective properties, but whether
      this extends to the BBB is unclear. We hypothesized that alcohol-induced
      disruption of brain microvascular endothelial barrier function and junctional
      protein organization can be ameliorated by S1P treatment. METHODS: Cultured
      primary HBMEC monolayers were used to characterize endothelial-specific
      mechanisms of BBB regulation. TER and apparent permeability coefficients for
      albumin, dextran-4 kDa, and sodium fluorescein were used as indices of barrier
      function. Junctional localization of Claudin-5, VE-cadherin, and beta-catenin was
      determined by immunofluorescence confocal microscopy. S1P was applied following
      treatment with alcohol. RESULTS: Alcohol significantly impaired HBMEC TER.
      Application of S1P after alcohol treatment resulted in a hastened recovery to the
      baseline HBMEC TER. Alcohol-treated HBMEC had a significantly higher mean
      permeability than control that was reversed by S1P. Alcohol caused the formation
      of gaps between cells. Treatment with S1P (after alcohol) increased junctional
      localization of VE-Cadherin, Claudin-5, and beta-catenin. CONCLUSIONS: Alcohol
      impairs the barrier function and junctional organization of HBMEC monolayers. S1P
      enhanced barrier function and restored junctions in the presence of alcohol, and
      thus may be useful for restoring BBB function during alcohol intoxication.

PMID- 30281889
TI  - Active K-RAS induces the coherent rotation of epithelial cells: A model for
      collective cell invasion in vitro.
AB  - At the invasive front of adenocarcinomas, single cells and multicellular
      structures exist; the latter include glands and cell clusters, such as tumor
      buddings and poorly differentiated clusters. Recent reports suggest the
      importance of collective cell migration in metastasis; however, it is technically
      difficult to observe the movement of multicellular structures in vivo. We
      utilized MDCK cells as a model for epithelial cells and established a method to
      quantify their motility in 3D structures in vitro. A single MDCK cell grows as a
      cell cluster in the gel and later proliferates and forms a cyst. Active K-RAS
      expression induced rotation of both the cell clusters and the cysts. The rotation
      speed of cell clusters was 4 times higher than that of cysts. The screening of
      inhibitors for their effects on cell clusters and cysts revealed that cyclin B1
      and beta-catenin were the key molecules for their rotation, respectively.
      Regulators for cyst rotation, such as vorinostat and beta-catenin, were not
      effective for inducing cell cluster rotation. These results indicate that the
      signaling pathways of cell dynamics are different between cell clusters and
      cysts. As cell clusters are related to lymph node involvement and the prognosis
      of various carcinomas, our in vitro quantitative system may be useful for the
      screening of drugs to prevent lymphatic invasion.

PMID- 30281890
TI  - Chemical cross-linking of a variety of green fluorescent proteins as Forster
      resonance energy transfer donors for Yukon orange fluorescent protein: A project
      based undergraduate laboratory experience.
AB  - Forster resonance energy transfer (FRET) is the basis for many techniques used in
      biomedical research. Due to its wide use in molecular sensing, FRET is commonly
      introduced in many biology, chemistry, and physics courses. While FRET is of
      great importance in the biophysical sciences, the complexity and difficulty of
      constructing FRET experiments has resulted in limited usage in undergraduate
      laboratory settings. Here, we present a practical undergraduate laboratory
      experiment for teaching FRET using a diverse set of green-emitting fluorescent
      proteins (FPs) as donors for a cross-linked Yukon orange FP. This laboratory
      experiment enables students to make the connection of basic lab procedures to
      real world applications and can be applied to molecular biology, biochemistry,
      physical chemistry, and biophysical laboratory courses. Published 2018. This
      article is a U.S. Government work and is in the public domain in the USA.,
      46(5):516-522, 2018.

PMID- 30281891
TI  - A metabolic control analysis approach to introduce the study of systems in
      biochemistry: the glycolytic pathway in the red blood cell.
AB  - Metabolic control analysis (MCA) is a promising approach in biochemistry aimed at
      understanding processes in a quantitative fashion. Here the contribution of
      enzymes and transporters to the control of a given pathway flux and metabolite
      concentrations is determined and expressed quantitatively by means of numerical
      coefficients. Metabolic flux can be influenced by a wide variety of modulators
      acting on one or more metabolic steps along the pathway. We describe a laboratory
      exercise to study metabolic regulation of human erythrocytes (RBCs). Within the
      framework of MCA, students use these cells to determine the sensitivity of the
      glycolytic flux to two inhibitors (iodoacetic acid: IA, and iodoacetamide: IAA)
      known to act on the enzyme glyceraldehyde-3-phosphate-dehydrogenase. Glycolytic
      flux was estimated by determining the concentration of extracellular lactate, the
      end product of RBC glycolysis. A low-cost colorimetric assay was implemented,
      that takes advantage of the straightforward quantification of the absorbance
      signal from the photographic image of the multi-well plate taken with a standard
      digital camera. Students estimate flux response coefficients for each inhibitor
      by fitting an empirical function to the experimental data, followed by analytical
      derivation of this function. IA and IAA exhibit qualitatively different patterns,
      which are thoroughly analyzed in terms of the physicochemical properties
      influencing their action on the target enzyme. IA causes highest glycolytic flux
      inhibition at lower concentration than IAA. This work illustrates the feasibility
      of using the MCA approach to study key variables of a simple metabolic system, in
      the context of an upper level biochemistry course. (c) 2018 International Union
      of Biochemistry and Molecular Biology, 46(5):502-515, 2018.

PMID- 30281892
TI  - An automatic skill evaluation framework for robotic surgery training.
AB  - BACKGROUND: To provide feedback to surgeons in robotic surgery training, many
      surgical skill evaluation methods have been developed. However, they hardly focus
      on the performance of the surgical motion segments. This paper proposes a method
      of specifying a trainee's skill weakness in the surgical training. METHODS: This
      paper proposed an automatic skill evaluation framework by comparing the trainees'
      operations with the template operation in each surgical motion segment, which is
      mainly based on dynamic time warping (DTW) and continuous hidden Markov model
      (CHMM). RESULTS: The feasibility of this proposed framework has been
      preliminarily verified. For specifying the skill weakness in instrument handling
      and efficiency, the result of this proposed framework was significantly
      correlated with that of manual scoring. CONCLUSION: The automatic skill
      evaluation framework has shown its superiority in efficiency, objectivity, and
      being targeted, which can be used in robotic surgery training.

PMID- 30281893
TI  - Effect of blue-light cystoscopy on contemporary performance of urine cytology.
AB  - OBJECTIVE: To evaluate the performance of urine cytology based on contemporary
      data, including the effect of enhanced cystoscopic techniques. MATERIALS AND
      METHODS: Individual patient data were obtained from three prospective studies:
      the Photocure (PC) B305 and the PC B308 studies, evaluating the use of blue-light
      cystoscopy with hexaminolevulinate (BLC-H), and the Cxbladder monitoring study,
      evaluating the Cxbladder monitor test for the detection of recurrent urothelial
      carcinoma. The specificity and sensitivity of cytology in each study and for the
      overall cohort were calculated. RESULTS: A total of 1 487 urine samples from 1
      375 patients were included in the analysis; overall 615 tumours were detected
      correlating to 41% of the cytological specimens. The pooled sensitivity and
      specificity for cytology were 40.8% and 92.8%, respectively. The pooled
      sensitivity was 11.4% for low-grade/World Health Organization (WHO) grade 1
      disease and 54.3% for high-grade/WHO grade 3 disease. There were no differences
      in cytology sensitivity based on the type of cystoscopy used, with sensitivity of
      41.3% and 40.4% in white-light cystoscopy (WLC) and BLC-H, respectively. Subgroup
      analysis including carcinoma in situ ( CIS) showed a trend towards lower cytology
      sensitivity in BLC-H (54.5%) vs WLC (69.2%). CONCLUSIONS: Based on analysis of
      contemporary data, the sensitivity of cytology for detecting high-grade tumours
      and CIS remains low. On a per-patient analysis, cytology sensitivity was not
      affected by the use of advanced cystoscopic techniques except in patients with
      CIS. The use of cytology as the main adjunct to cystoscopy in patients at high
      risk can lead to missed opportunities for early detection of recurrence and for
      determining which patients are not responding to intravesical therapies such as
      bacille Calmette-Guerin.

PMID- 30281894
TI  - Physical models can provide superior learning opportunities beyond the benefits
      of active engagements.
AB  - The essence of molecular biology education lies in understanding of gene
      expression, with subtopics including the central dogma processes, such as
      transcription and translation. While these concepts are core to the discipline,
      they are also notoriously difficult for students to learn, probably because they
      cannot be directly observed. While nearly all active learning strategies have
      been shown to improve learning compared with passive lectures, little has been
      done to compare different types of active learning. We hypothesized that physical
      models of central dogma processes would be especially helpful for learning,
      because they provide a resource that students can see, touch, and manipulate
      while trying to build their knowledge. For students enrolled in an entirely
      active-learning-based Cell & Molecular Biology course, we examined whether model
      based activities were more effective than non-model based activities. To test
      their understanding at the beginning and end of the semester, we employed the
      multiple-select Central Dogma Concept Inventory (CDCI). Each student acted as
      their own control, as all students engaged in all lessons yet some questions
      related to model-based activities and some related to clicker questions, group
      problem-solving, and other non-model-based activities. While all students
      demonstrated learning gains on both types of question, they showed much higher
      learning gains on model-based questions. Examining their selected answers in
      detail showed that while higher performing students were prompted to refine their
      already-good mental models to be even better, lower performing students were able
      to construct new knowledge that was much more consistent with an expert's
      understanding. (c) 2018 The Authors. Biochemistry and Molecular Biology Education
      published by Wiley Periodicals, Inc. on behalf of International Union of
      Biochemistry and Molecular Biology., 46(5):435-444, 2018.

PMID- 30281895
TI  - Changing trends in the endourological management of urolithiasis in anomalous
      kidneys.
AB  - OBJECTIVES: To present our single-centre experience of urolithiasis management in
      anomalous kidneys, highlighting the need for an algorithm-based approach in
      deciding the appropriate treatment method for each type. PATIENTS AND METHODS: We
      retrospectively reviewed the data of all the patients who presented to our renal
      unit with urolithiasis in an anomalous kidney between January 1990 and July 2014.
      The peri-operative characteristics of all the patients, along with management
      approach, were studied. RESULTS: Percutaneous nephrolithotomy (PCNL) was the most
      common surgical technique used, followed by flexible ureterorenoscopy (URS). Pain
      was the most common presentation in these patients. The overall stone clearance
      rate associated with PCNL and flexible URS was 85.8% in cases of anomalous
      kidneys in this series. The stone clearance rates in ectopic kidneys, horseshoe
      kidneys, malrotated kidneys and autosomal dominant polycystic kidneys associated
      with PCNL and flexible URS were similar: 86%, 88%, 76% and 83%, respectively, and
      81.2%, 80%, 92% and 100%, respectively . Based on our results, we developed a
      stone management algorithm. CONCLUSION: The management of renal calculi in
      patients with renal anomalies may vary based on the stone size, location,
      density, pelvicalyceal system anatomy and drainage. An algorithm-based approach
      could help surgeons decide the appropriate treatment in this population.

PMID- 30281896
TI  - Discontinuation of antidepressants in suicides findings from the Friuli Venezia
      Giulia Region, Italy, 2005-2014.
AB  - Although continued use of antidepressants (AD) has been found to be associated
      with a lower risk of suicide, AD discontinuation is reported repeatedly. The aim
      of this case-control study, thus, was to assess whether discontinuation to AD was
      associated with an increased risk of suicide, according to different genders and
      age groups. The Social and Health Information System of Friuli Venezia Giulia
      Region, Italy, was used to collect data on suicides, diagnoses and AD use from
      2005 to 2014. We selected, as cases, all suicides that had at least one
      prescription of AD in the 730 days before death (N = 876), and we matched with
      regard to age and sex each case with five controls from the general population.
      Conditional logistic regression analyses were used to assess the association
      between suicide and modifications of AD treatment. We found that 70% of suicides
      and controls from the general population discontinued AD in the 2 years before
      the index date. In two-thirds of them, discontinuations were two or more.
      Discontinuation of AD, however, did not represent a significant risk factor for
      suicide. More appropriate care of depression, particularly by primary care
      physicians who widely prescribe AD, should be fostered in order to prevent
      suicide. However, more research is needed to assess to which extent AD
      discontinuation can affect suicidal risk.

PMID- 30281897
TI  - Reply to the letter: "Center effect on posttransplant survival among currently
      active United States pediatric heart transplant centers".

PMID- 30281898
TI  - 'It depends what you mean by leadership': An analysis of stakeholder perspectives
      on consumer leadership.
AB  - Contemporary mental health policies call for increased involvement of consumers
      in leadership across mental health service design, delivery, and evaluation.
      However, consumer leadership is not currently well understood within academia or
      in mental health services themselves. This study investigates how consumer
      leadership is currently conceptualized by stakeholders at the service delivery
      level. To this end, semistructured interviews were conducted with 14 mental
      health organization members identifying as consumer leaders, colleagues
      supporting consumer leaders, or organization executives. Interview data were
      analysed using an inductive thematic analysis to develop a broad understanding of
      participants' perceptions of consumer leadership. Findings indicate constructions
      of consumer leadership within mental health organizations can be understood in
      relation to four themes: consumer leadership roles, requirements, purpose, and
      process. Inconsistencies across participants' perceptions of consumer leadership
      were identified as constituting barriers to its development, highlighting the
      need to better clarify the nature of consumer leadership.

PMID- 30281899
TI  - A novel patient-specific three-dimensional drug delivery construct for
      regenerative endodontics.
AB  - Evoked bleeding (EB) clinical procedure, comprising a disinfection step followed
      by periapical tissue laceration to induce the ingrowth of undifferentiated stem
      cells from the periodontal ligament and alveolar bone, is currently the only
      regenerative-based therapeutic approach to treating pulp tissue necrosis in
      undeveloped (immature) permanent teeth approved in the United States. Yet, the
      disinfection step using antibiotic-based pastes leads to cytotoxic, warranting a
      biocompatible strategy to promote root canal disinfection with no or minimal side
      effects to maximize the regenerative outcomes. The purpose of this investigation
      was to develop a tubular three-dimensional (3D) triple antibiotic-eluting
      construct for intracanal drug delivery. Morphological (scanning electron
      microscopy), chemical (Fourier transform infrared spectroscopy), and mechanical
      (tensile testing) characteristics of the polydioxanone-based triple antibiotic
      eluting fibers were assessed. The antimicrobial properties of the tubular 3D
      constructs were determined in vitro and in vivo using an infected (Actinomyces
      naeslundii) dentin tooth slice model and a canine method of periapical disease,
      respectively. The in vitro data indicated significant antimicrobial activity and
      the ability to eliminate bacterial biofilm inside dentinal tubules. In vivo
      histological findings demonstrated that, using the EB procedure, the tubular 3D
      triple antibiotic-eluting construct allowed the formation of an appropriate
      environment that led to apex closure and the ingrowth of a thin layer of
      osteodentin-like tissue into the root canal. Taken together, these findings
      indicate that our novel drug delivery construct is a promising biocompatible
      disinfection strategy for immature permanent teeth with necrotic pulps. (c) 2018
      Wiley Periodicals, Inc. J Biomed Mater Res B Part B, 2018.

PMID- 30281900
TI  - Using of keratin substrate for enrichment of HT29 colorectal cancer stem-like
      cells.
AB  - Eradication of cancer stem-like cells (CSLCs) are becoming increasingly an
      important target for new cancer therapies. The ability to study their behavior in
      vitro will provide the opportunity for high-throughput testing of more effective
      treatments. In this study, spheroid-like structures' formation and enrichment of
      HT29 CSLCs were evaluated on a wool keratin-based substrate as a bio-mimic of
      natural extracellular matrix (ECM) proteins. The results indicated that culturing
      on keratin substrate increased spheroid formation ability and radio
      /chemoresistance of HT29 cells. Moreover, cell surface expression of CD133 CSLCs'
      marker and the mRNA level of stemness genes such as Nanog, Oct4, and c-MYC were
      increased. These data suggest that keratin can potentially be used for spheroid
      like structure formation and enrichment of HT29 CSLCs. In addition, it seems that
      the induction of stemness characteristics on keratin substrate is probably
      because of the activation of alpha2 beta1 integrin signaling pathway. (c) 2018
      Wiley Periodicals, Inc. J Biomed Mater Res B Part B: Appl Biomater, 2018.

PMID- 30281901
TI  - Group A Streptococcus puerperal sepsis: an emerging obstetric infection?

PMID- 30281902
TI  - A combined lipidomic and 16S rRNA gene amplicon sequencing approach reveals
      archaeal sources of intact polar lipids in the stratified Black Sea water column.
AB  - Archaea are important players in marine biogeochemical cycles, and their membrane
      lipids are useful biomarkers in environmental and geobiological studies. However,
      many archaeal groups remain uncultured and their lipid composition unknown. Here,
      we aim to expand the knowledge on archaeal lipid biomarkers and determine the
      potential sources of those lipids in the water column of the euxinic Black Sea.
      The archaeal community was evaluated by 16S rRNA gene amplicon sequencing and by
      quantitative PCR. The archaeal intact polar lipids (IPLs) were investigated by
      ultra-high-pressure liquid chromatography coupled to high-resolution mass
      spectrometry. Our study revealed both a complex archaeal community and large
      changes with water depth in the IPL assemblages. In the oxic/upper suboxic waters
      (<105 m), the archaeal community was dominated by marine group (MG) I
      Thaumarchaeota, coinciding with a higher relative abundance of hexose
      phosphohexose crenarchaeol, a known marker for Thaumarchaeota. In the suboxic
      waters (80-110 m), MGI Nitrosopumilus sp. dominated and produced predominantly
      monohexose glycerol dibiphytanyl glycerol tetraethers (GDGTs) and hydroxy-GDGTs.
      Two clades of MGII Euryarchaeota were present in the oxic and upper suboxic zones
      in much lower abundances, preventing the detection of their specific IPLs. In the
      deep sulfidic waters (>110 m), archaea belonging to the DPANN Woesearchaeota,
      Bathyarchaeota, and ANME-1b clades dominated. Correlation analyses suggest that
      the IPLs GDGT-0, GDGT-1, and GDGT-2 with two phosphatidylglycerol (PG) head
      groups and archaeol with a PG, phosphatidylethanolamine, and phosphatidylserine
      head groups were produced by ANME-1b archaea. Bathyarchaeota represented 55% of
      the archaea in the deeper part of the euxinic zone and likely produces archaeol
      with phospho-dihexose and hexose-glucuronic acid head groups.

PMID- 30281903
TI  - A mitochondrial ROS pathway controls matrix metalloproteinase 9 levels and
      invasive properties in RAS-activated cancer cells.
AB  - Matrix metalloproteinases (MMPs) are tissue-remodeling enzymes involved in the
      processing of various biological molecules. MMPs also play important roles in
      cancer metastasis, contributing to angiogenesis, intravasation of tumor cells,
      and cell migration and invasion. Accordingly, unraveling the signaling pathways
      controlling MMP activities could shed additional light on cancer biology. Here,
      we report a molecular axis, comprising the molecular adaptor hydrogen peroxide
      inducible clone-5 (HIC-5), NADPH oxidase 4 (NOX4), and mitochondria-associated
      reactive oxygen species (mtROS), that regulates MMP9 expression and may be a
      target to suppress cancer metastasis. We found that this axis primarily
      downregulates mtROS levels which stabilize MMP9 mRNA. Specifically, HIC-5
      suppressed the expression of NOX4, the source of the mtROS, thereby decreasing
      mtROS levels and, consequently, destabilizing MMP9 mRNA. Interestingly, among six
      cancer cell lines, only EJ-1 and MDA-MB-231 cells exhibited upregulation of NOX4
      and MMP9 expression after shRNA-mediated HIC-5 knockdown. In these two cell
      lines, activating RAS mutations commonly occur, suggesting that the HIC-5
      mediated suppression of NOX4 depends on RAS signaling, a hypothesis that was
      supported experimentally by the introduction of activated RAS into mammary
      epithelial cells. Notably, HIC-5 knockdown promoted lung metastasis of MDA-MB-231
      cancer cells in mice. The tumor growth of HIC-5-silenced MDA-MB-231 cells at the
      primary sites was comparable to that of control cells. Consistently, the invasive
      properties of the cells, but not their proliferation, were enhanced by the HIC-5
      knockdown in vitro. We conclude that NOX4-mediated mtROS signaling increases MMP9
      mRNA stability and affects cancer invasiveness but not tumor growth.

PMID- 30281904
TI  - Dosage and composition of bioactive glasses differentially regulate angiogenic
      and osteogenic response of human MSCs.
AB  - Vascularization of the fracture site and cell-mediated deposition of the
      mineralized matrix are crucial determinants for successful bone regeneration
      after injury. Ceramic biomaterials such as bioactive glasses (BAGs) that release
      bioactive ions have shown promising results in bone defect regeneration. However,
      it remains unclear how the dosage and composition of bioactive ions influence the
      angiogenic and osteogenic behavior of primary human mesenchymal stromal cells
      (MSCs). Here, we show that exposure to ionic dissolution products from 1393 and
      45S5 BAGs can evoke distinct angiogenic and osteogenic responses from primary
      MSCs in a dose- and composition-dependent manner. Significantly higher
      concentrations of the pro-angiogenic factors VEGF, HGF, PIGF, angiopoietin, and
      angiogenin were detected in conditioned media (CM) from MSCs exposed to 45S5, but
      not 1393, BAGs. Application of this CM to human umbilical vein endothelial cells
      (HUVECs) resulted in robust 2D tube formation in vitro. Osteogenic
      differentiation of MSCs was assessed by gene expression analysis and
      mineralization assays. Low concentrations (0.1% w/v) of 1393 BAGs significantly
      enhanced the gene expression of RUNX2 and ALP and induced an earlier onset of
      matrix mineralization compared to all other groups. We further tested whether
      simultaneous exposure to both BAGs would improve both angiogenic secretion and
      osteogenic differentiation of MSCs, and did not find evidence to support this
      hypothesis. Our results provide evidence of BAG composition-dependent enhancement
      of primary human MSCs' regenerative function, besides also underlining the
      importance of an in vitro evaluation of the dose-response relationship to
      translate BAG based approaches into safe and effective clinical therapies. (c)
      2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2827-2837, 2018.,
      2018.

PMID- 30281905
TI  - Development of novel PLGA nanoparticles with co-encapsulation of docetaxel and
      abiraterone acetate for a highly efficient delivery into tumor cells.
AB  - Co-encapsulation of abiraterone acetate (AbrA) and docetaxel (Dtx) in polymeric
      nanoparticles as novel prototypes for prostate cancer treatment combining
      hormonal and chemotherapy was designed. Nanoparticles (NPs) composed of poly(dl
      lactide-co-glycolide) (PLGA) were prepared by single-emulsion solvent evaporation
      technique and characterized in terms of morphology with atomic force microscopy
      and transmission electron microscopy. HPLC method for simultaneous determination
      of AbrA and Dtx encapsulation efficacy was developed. Also differential scanning
      calorimetry and Fourier-transform infrared spectroscopy were provided. To study
      the effectiveness of cellular internalization and distribution of NPs with AbrA
      and Dtx co-encapsulation (NP-AbrA/Dtx), a fluorescence microscopy was utilized.
      NPs prepared had size 256.3 +/-9.4 nm and zeta potential -18.4 +/-1.4 mV.
      Encapsulation efficacy for AbrA was 68.7% and for Dtx was 74.3%. NPs were able to
      control the AbrA and Dtx release within 24 h. The mathematical model of drug
      release was performed. The results obtained from confocal microscopy showed the
      effective accumulation of the NP-AbrA/Dtx in the cytoplasm of cells. Synthesized
      NPs possessed satisfactory parameters and a biphasic release profile, proceeding
      by the Fick diffusion mechanism, which provide prolonged release of the drugs and
      maintenance of their concentration. It was shown that NPs loaded with AbrA and
      Dtx exhibited a high cytotoxic activity on the LNCaP cell line, similar to the
      combination of free drugs of AbrA and Dtx, but in contrast to the combination of
      substances, had a synergistic mechanism of action. Our findings support the
      potential use of developed NPs in further in vivo studies. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B, 2018.

PMID- 30281906
TI  - Monolithic thin-layer chromatography plates with covalently bonded matrix for
      hyphenation with matrix-assisted laser desorption/ionization.
AB  - Monolithic layers prepared by the copolymerization of ethylene dimethacrylate and
      glycidyl methacrylate and deposited onto the surface of glass and silicon plates
      were investigated as thin-layer chromatography separation media in hyphenated
      thin-layer chromatography with matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) analysis. Varying composition of the polymerization
      mixture and polymerization conditions layers of different porosities and MALDI-MS
      compatibility were synthesized. Compatibility with MALDI-MS was tested using
      polyethylene glycol and it was demonstrated that layers prepared without glycidyl
      methacrylate are not compatible with MALDI-MS and do not allow obtaining any mass
      spectra. Best results were achieved with layers containing 19 to 29% glycidyl
      methacrylate. These layers allow the measurement of mass spectra without
      additional depositing matrix compounds supplying mass spectra almost "clean" in
      low molar mass range.

PMID- 30281907
TI  - Novel applications of nonwood cellulose for blood typing assays.
AB  - Paper-based microfluidics devices can create a new healthcare model. Cellulose is
      carbohydrate polymer biocompatible and hydrophilic. These characteristics enhance
      the development of user-friendly diagnostic devices, but the link between paper
      manufacturing process and performance of the devices is still unclear. Previous
      studies focused on either commercial papers or lab papers from wood-cellulose
      fibers, with different basis-weight. This work introduces the effect of refining
      process and lab paper from nonwood-cellulose fibers, focusing on sisal fibers to
      overcome the aforementioned challenge. Structural characteristics of paper, such
      as basis-weight and degree of refining, are optimized and correlated with blood
      typing test resolution. Unrefined sisal paper of 50 g/m2 and 100 g/m2 basis
      weight exhibit a higher gray intensity level than refined paper, and also maximal
      capillary rise and a pore size suitable for blood grouping tests. Two different
      blood types were evaluated with results consistent with the traditional methods,
      testifying the usefulness of this methodology. (c) 2018 Wiley Periodicals, Inc.
      J. Biomed. Mater. Res. Part B, 2018.

PMID- 30281908
TI  - Preparation of photothermal palmitic acid/cholesterol liposomes.
AB  - Indocyanine green (ICG) is the only FDA-approved near-infrared dye and it is
      currently used clinically for diagnostic applications. However, there is
      significant interest in using ICG for triggered drug delivery applications and
      heat ablation therapy. Unfortunately, free ICG has a short half-life in vivo and
      is rapidly cleared from circulation. Liposomes have been frequently used to
      improve ICG's stability and overall time of effectiveness in vivo, but they have
      limited stability due to the susceptibility of phospholipids to hydrolysis and
      oxidation. In this study, nonphospholipid liposomes were used to encapsulate ICG,
      and the resulting liposomes were characterized for size, encapsulation
      efficiency, stability, and photothermal response. Using the thin-film hydration
      method, an ICG encapsulation efficiency of 54% was achieved, and the liposomes
      were stable for up to 12 weeks, with detectable levels of encapsulated ICG up to
      week 4. Additionally, ICG-loaded liposomes were capable of rapidly producing a
      significant photothermal response upon exposure to near-infrared light, and this
      photothermal response was able to induce changes in the mechanical properties of
      thermally responsive hydrogels. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater
      Res B Part B, 2018.

PMID- 30281909
TI  - Rate-limiting step and substrate accessibility of cellobiohydrolase Cel6A from
      Trichoderma reesei.
AB  - The cellobiohydrolase (CBH) Cel6A is an important component of enzyme cocktails
      for industrial degradation of lignocellulosic biomass. However, the kinetics of
      this enzyme acting on its natural, insoluble substrate remains sparsely
      investigated. Here, we studied Cel6A from Trichoderma reesei with respect to
      adsorption, processivity, and kinetics both in the steady-state and pre-steady
      state regimes, on microcrystalline and amorphous cellulose. We found that slow
      dissociation (koff ) was limiting the overall reaction rate, and we suggest that
      this leads to an accumulation of catalytically inactive complexes in front of
      obstacles and irregularities on the cellulose surface. The processivity number of
      Cel6A was low on both investigated substrates (5-10), and this suggested a rugged
      surface with short obstacle-free path lengths. The turnover of the inner
      catalytic cycle (the reactions of catalysis in one processive step) was too fast
      to be fully resolved, but a minimum value of about 20 s-1 could be established.
      This is among the highest values reported hitherto for a cellulase, and it
      underscores the catalytic efficiency of Cel6A. Conversely, we found that Cel6A
      had a poor ability to recognize attack sites on the cellulose surface. On
      amorphous cellulose, for example, Cel6A was only able to initiate hydrolysis on
      about 4% of the sites to which it could adsorb. This probably reflects high
      requirements of Cel6A to the architecture of the site. We conclude that compared
      to the other CBH, Cel7A, secreted by T. reesei, Cel6A is catalytically more
      efficient but less capable of attacking a broad range of structurally distinct
      sites on the cellulose surface. ENZYMES: TrCel6A, nonreducing end-acting
      cellobiohydrolase (EC3.2.1.91) from Trichoderma reesei; TrCel7A, reducing end
      acting cellobiohydrolase (EC3.2.1.176) from T. reesei.

PMID- 30281910
TI  - Molecular phylogenetics of Newcastle disease viruses isolated from vaccinated
      flocks during outbreaks in Southern India reveals circulation of a novel sub
      genotype.
AB  - Newcastle disease (ND) is an economically important, contagious poultry viral
      disease reported across the globe. In India, ND is endemic and episodes of ND
      outbreaks despite strict vaccinations are not uncommon. We isolated and
      characterized seven ND viruses from vaccinated commercial poultry farms during
      severe disease outbreaks in Tamil Nadu, in Southern India, between April 2015 and
      June 2016. All the seven isolates were categorized as virulent by mean death time
      (48-54 hr) in embryonated chicken eggs. Also, their sequences carried the
      virulence signature of multi-basic amino acid residues in their fusion protein
      cleavage site (RRQ/RR/KRF). Phylogenetic and evolutionary distance analyses
      revealed circulation of a novel sub-genotype of genotype XIII, class II ND
      viruses, herein proposed as sub-genotype XIIIe. The genetic divergence between
      the circulating virulent strains and the vaccine strains could possibly explain
      the disease outbreak in the vaccinated flocks. Further, our study signifies the
      need to implement routine epidemiological surveillance and to revisit the current
      vaccination program.

PMID- 30281911
TI  - Does mitochondrial DNA evolution in metazoa drive the origin of new mitochondrial
      proteins?
AB  - Most eukaryotic cells contain mitochondria with a genome that evolved from their
      alpha-proteobacterial ancestor. In the course of eukaryotic evolution, the
      mitochondrial genome underwent a dramatic reduction in size, caused by the loss
      and translocation of genes. This required adjustments in mitochondrial gene
      expression mechanisms and resulted in a complex collaborative system of
      mitochondrially encoded transfer RNAs and ribosomal RNAs with nuclear encoded
      proteins to express the mitochondrial encoded oxidative phosphorylation (OXPHOS)
      proteins. In this review, we examine mitochondrial gene expression from an
      evolutionary point of view: to what extent can we correlate changes in the
      mitochondrial genome in the evolutionary lineage leading to human with the origin
      of new nuclear encoded proteins. We dated the evolutionary origin of
      mitochondrial proteins that interact with mitochondrial DNA or its RNA and/or
      protein products in a systematic manner and compared them with documented changes
      in the mitochondrial DNA. We find anecdotal but accumulating evidence that
      metazoan RNA-interacting proteins arose in conjunction with changes of the
      mitochondrial DNA. We find no substantial evidence for such compensatory
      evolution in new OXPHOS proteins, which appear to be constrained by the ability
      to form supercomplexes. (c) 2018 IUBMB Life, 70(12):1240-1250, 2018.

PMID- 30281912
TI  - Poly r(C) Binding Protein 1 Regulates Posttranscriptional Expression of the
      Ubiquitin Ligase TRIM56 in Ovarian Cancer.
AB  - Our earlier work has shown that the E3 ligase TRIM56 messenger RNA (mRNA) level
      and vimentin protein expression followed an inverse correlation in ovarian
      carcinoma patients; however, the regulatory mechanisms underlying TRIM56
      expression is unclear. Steady state expression of TRIM56 mRNA expression in the
      normal ovarian cell line Moody and ovarian cancer cell lines SKOV-3, A2780, and
      Caov-3 were not significantly different; however, TRIM56 protein expression was
      significantly lower in the ovarian cancer cell lines compared to the Moody cell
      line. Polysome profiling showed significant increase in translation of TRIM56
      messenger RNA in the Moody cells compared to the SKOV-3 cells. We performed RNA
      affinity pulldown using biotinylated TRIM56 5 'and 3'-UTR and postnuclear
      extracts from Moody and SKOV-3 cells. Whereas no notable difference was observed
      in affinity pull-down obtained with the 5'-UTR, there was obvious difference in
      protein binding patterns with the 3'-UTR. Mass spectrometry was used to determine
      the most differentially binding protein as poly r (c) binding protein 1 (PCBP1).
      PCBP1 expression and binding to the 3'-UTR was both higher in SKOV-3 cells
      compared to the Moody cells. Silencing of TRIM56 in Moody cells cause an increase
      in in vitro migration and invasion, and a similar effect was mimicked by
      overexpression of PCBP1. Conversely, silencing of PCBP1 or overexpression of
      TRIM56 in SKOV-3 cells significantly decreased in vitro migration and invasion.
      In xenograft assays, SKOV-3 cells stably overexpressing shRNA targeting PCBP1
      decreased metastasis, whereas shRNA-targeting TRIM56 potentiated detection of
      metastatic lesions, compared to the parental SKOV-3 cells themselves. Taken
      together our results reveal a yet undefined posttranscriptional regulatory
      mechanism underlying low expression of TRIM56 in ovarian cancer. (c) 2018 IUBMB
      Life, 9999(9999):1-6, 2018.

PMID- 30281914
TI  - Up-regulation and tumor-promoting role of SPHK1 were attenuated by miR-330-3p in
      gastric cancer.
AB  - We intended to clarify the role of sphingosine kinase 1 (SPHK1) in gastric cancer
      (GC) using both in vitro and in vivo assays. The study was designed to identify
      novel therapeutic targets for GC treatment. Differential analysis was utilized to
      dissect two gene expression omnibus series (GSE49515 and GSE79973) microarray
      data form Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/)
      dataset. MRNA and protein expressions were determined by quantitative polymerase
      chain reaction and Western blot, respectively. GC cell growth was measured by MTT
      assays and verified by in vivo analysis. Cell cycle and cell apoptosis were
      detected via flow cytometer observation. Cell migration and invasion were
      assessed by wound healing assays and Transwell assays. The targeting relationship
      between miRNA and SPHK1/S1PR1 was identified via dual-luciferase assay. Twenty
      four common differentially expressed genes were screened out from two gene
      expression omnibus series (GSE49515 and GSE79973), among which SPHK1 was chosen
      for its higher fold change. We found elevated SPHK1 expression in GC tissues and
      cells, along with an increased concentration of SPHK1-generated sphingosine-1
      phosphate (S1P) in both GC serum and tissue. SPHK1 knockdown significantly
      suppressed cell proliferation, migration, and invasion of MKN1 and KATO3 cells.
      It also blocked cell cycle and induced apoptosis in MKN1 and KATO3 cells.
      Silencing of SPHK1 also refrained tumor growth and inhibited S1P level. MiR-330
      3p directly targeted SPHK1 and S1PR1. Overexpressed miR-330-3p in MKN1 cells
      repressed SPHK1 and S1PR1 expressions like their chemical inhibitors-SPHK1
      inhibitors (FTY720) and S1PR1 inhibitors (VPC23019), and acted anti-tumor both in
      vitro and in vivo. Our study provides evidence that SPHK1 was promotive for GC
      tumor growth and cell biological behaviors, and that miR-330-3p targeted 3'-UTR
      of SPHK1 and inhibited its expression. SPHK1 was expected to become a new
      molecular marker and miR-330-3p a novel therapeutic target for GC. (c) 2018 IUBMB
      Life, 70(11):1164-1176, 2018.

PMID- 30281913
TI  - An improved method for utilizing high-throughput amplicon sequencing to determine
      the diets of insectivorous animals.
AB  - DNA analysis of predator feces using high-throughput amplicon sequencing (HTS)
      enhances our understanding of predator-prey interactions. However, conclusions
      drawn from this technique are constrained by biases that occur in multiple steps
      of the HTS workflow. To better characterize insectivorous animal diets, we used
      DNA from a diverse set of arthropods to assess PCR biases of commonly used and
      novel primer pairs for the mitochondrial gene, cytochrome oxidase C subunit 1
      (COI). We compared diversity recovered from HTS of bat guano samples using a
      commonly used primer pair "ZBJ" to results using the novel primer pair "ANML". To
      parameterize our bioinformatics pipeline, we created an arthropod mock community
      consisting of single-copy (cloned) COI sequences. To examine biases associated
      with both PCR and HTS, mock community members were combined in equimolar amounts
      both pre- and post-PCR. We validated our system using guano from bats fed known
      diets and using composite samples of morphologically identified insects collected
      in pitfall traps. In PCR tests, the ANML primer pair amplified 58 of 59 arthropod
      taxa (98%) whereas ZBJ amplified 24-40 of 59 taxa (41-68%). Furthermore, in an
      HTS comparison of field-collected samples, the ANML primers detected nearly four
      fold more arthropod taxa than the ZBJ primers. The additional arthropods detected
      include medically and economically relevant insect groups such as mosquitoes.
      Results revealed biases at both the PCR and sequencing levels, demonstrating the
      pitfalls associated with using HTS read numbers as proxies for abundance. The use
      of an arthropod mock community allowed for improved bioinformatics pipeline
      parameterization. This article is protected by copyright. All rights reserved.

PMID- 30281915
TI  - Adoptive cell therapy of tolerogenic dendritic cells as inducer of regulatory T
      cells in allergic rhinitis.
AB  - BACKGROUND: Regulatory T cells (Tregs) have become promising candidates for
      immunotherapy in allergic rhinitis (AR). The contributing role of tolerogenic
      dendritic cells (tDCs) in the augmentation of Tregs in AR remains to be
      determined. METHODS: The properties of tDCs in expanding Tregs and their
      potential to ameliorate AR were evaluated in vitro and in vivo. RESULTS: Monocyte
      derived tDCs stimulated with Dermatophagoides pteronyssinus allergen 1 favored
      the generation of activated Tregs (aTregs) and suppressed effector T-cell
      responses in a transforming growth factor-beta/interleukin-10 (TGF-beta/IL-10)
      dependent manner in vitro. The adoptive transfer of tDCs inhibited allergic
      airway inflammation in the mouse model, whereas depletion of CD25+ cells or
      blocking TGF-beta/IL-10 signaling eliminated the inhibitory effect, indicating
      that Tregs were involved in the anti-inflammatory activity of tDCs. CONCLUSION:
      Our data show that tDCs are a potential therapeutic target in AR.

PMID- 30281916
TI  - Alterations of EDEM1 functions enhance ATF6 pro-survival signaling.
AB  - Activating transcription factor 6 alpha (referred to as ATF6 hereafter) is an
      endoplasmic reticulum (ER)-resident glycoprotein and one of the three sensors of
      the unfolded protein response (UPR). Upon ER stress, ATF6 is exported to the
      Golgi complex where it is cleaved by the S1P and S2P proteases thus releasing
      ATF6 cytosolic fragment and leading to the transcription of ATF6 target genes. In
      this study, we performed a phenotypic small-interfering RNA (siRNA) screening to
      better characterize the ER mechanisms involved in ATF6 activation upon ER stress.
      This revealed that silencing of ER-degradation-enhancing alpha-mannosidase-like
      protein-1 (EDEM1) increased the bioavailability of ER stress-induced ATF6 export
      to the Golgi complex through the stabilization of the natively unstable ATF6
      protein. Moreover, we characterized a somatic variant of EDEM1 (N198I) found in
      hepatocellular carcinoma that alters ATF6 signaling and might provide a selective
      advantage to the transforming cells. Hence, our work confirms the natively
      unstable nature of ATF6 and links this property to potentially associated pro
      oncogenic functions.

PMID- 30281917
TI  - Radiotherapy patterns of care for stage I and II non-small cell lung cancer in
      Sydney, Australia.
AB  - INTRODUCTION: Curative radiotherapy is guideline treatment for inoperable
      patients of good performance status with Stage I & II Non-Small Cell Lung Cancer
      (NSCLC). The aim of this study was to evaluate radiotherapy patterns of care in
      these patients, the reasons for palliative treatment and the proportion of
      patients suitable for curative stereotactic ablative body radiotherapy (SABR).
      METHODS: Electronic oncology databases at three institutions were queried to
      retrieve data on patients with inoperable Stage I & II NSCLC seen in radiation
      oncology clinics between 1/1/2008 and 31/12/2014. Suitability for SABR was
      defined as peripheral tumours less than 5 cm in size. Factors associated with
      curative treatment were determined using univariate and multivariate analyses.
      RESULTS: Three-hundred-and-twelve patients were identified of whom 178 (57%)
      received curative radiotherapy, 58 (19%) palliative radiotherapy and 76 (24%) no
      radiotherapy. The main reason for receiving palliative rather than curative
      treatment was COPD or poor pulmonary function (26%). Method of diagnosis (P =
      0.031), Simplified Comorbidity Score (P = 0.003), ECOG performance status (P =
      0.016), FEV1% (P = 0.040), treating institution (P < 0.0001) and time period (P =
      0.016) were associated with curative radiotherapy on multivariate analysis. In
      patients with T1-2N0M0 NSCLC, 19 (31%) who did not receive treatment and 7 (21%)
      who underwent palliative radiotherapy were technically and clinically suitable
      for SABR. CONCLUSION: Only 57% of patients with Stage I-II NSCLC were treated
      with curative radiotherapy. Patient factors were the predominant reason for
      palliative treatment, however, treating institution also played a role. A
      considerable proportion of patients who underwent palliative or no radiotherapy
      were suitable for SABR treatment.

PMID- 30281919
TI  - NT5E inhibition suppresses the growth of sunitinib-resistant cells and EMT course
      and AKT/GSK-3beta signaling pathway in renal cell cancer.
AB  - We aimed to explore the mechanisms of sunitinib-resistance in renal cell cancer
      (RCC) and provide new therapeutic evidence and biomarkers for RCC treatment using
      human clear-cell renal cell carcinoma (ccRCC) cell line, 786-O. Microarray
      analysis, quantitative real time PCR (qRT-PCR), Western blot, and
      immunohistochemistry were used to detect Ecto-5'-nucleotidase (NT5E) expressions
      in sunitinib-resistant tissues in RCC. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl
      2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT), cell-count kit
      8 (CCK-8), wound healing, and Transwell assays were used to investigate the
      influences of sunitinib and NT5E on 786-O cell line and sunitinib-resistant 786-O
      cell line (S786-O). Protein expressions related to epithelial-mesenchymal
      transition (EMT) and AKT/GSK-3beta signaling pathway in 786-O cells and S786-O
      cells were determined by Western blot. In vivo experiment was performed using NCr
      nu/nu mice to explore the effects of NT5E on cell growth and EMT signal in
      sunitinib environment. NT5E expression was upregulated in sunitinib-resistant RCC
      tissues and cells. NT5E downregulation repressed RCC cell proliferation,
      migration as well as invasion. EMT course and AKT/GSK-3beta signal pathway both
      in vitro and in vivo in sunitinib environment was suppressed to varying degrees
      via NT5E inhibition. NT5E inhibition could suppress the growth of sunitinib
      resistant RCC cells and restrain EMT course and AKT/GSK-3beta signal pathway in
      sunitinib environment in RCC. (c) 2018 IUBMB Life, 2018.

PMID- 30281918
TI  - Assessment of tumour response after stereotactic ablative radiation therapy for
      lung cancer: A prospective quantitative hybrid 18 F-fluorodeoxyglucose-positron
      emission tomography and CT perfusion study.
AB  - INTRODUCTION: Stereotactic ablative radiotherapy (SABR) is a guideline
      recommended treatment for inoperable stage I non-small cell lung cancer (NSCLC),
      but imaging assessment of response after SABR is difficult. The goal of this
      study was to evaluate imaging-based biomarkers of tumour response using dynamic
      18 F-FDG-PET and CT perfusion (CTP). METHODS: Thirty-one patients with early
      stage NSCLC participated in this prospective correlative study. Each underwent
      dynamic 18 F-FDG-PET/CTP studies on a PET/CT scanner pre- and 8 weeks post-SABR.
      The dynamic 18 F-FDG-PET measured the tumour SUVmax , SUVmean and the following
      parameters: K1 , k2 , k3 , k4 and Ki , all using the Johnson-Wilson-Lee kinetic
      model. CTP quantitatively mapped BF, BV, MTT and PS in tumours and measured
      largest tumour diameter. Since free-breathing was allowed during CTP scanning,
      non-rigid image registration of CT images was applied to minimize misregistration
      before generating the CTP functional maps. Differences between pre- and post-SABR
      imaging-based parameters were compared. RESULTS: Tumour size changed only
      slightly after SABR (median 26 mm pre-SABR vs. 23 mm post-SABR; P = 0.01).
      However, dynamic 18 F-FDG-PET and CTP study showed substantial and significant
      changes in SUVmax , SUVmean , k3 , k4 and Ki . Significant decreases were evident
      in SUVmax (median 6.1 vs. 2.6; P < 0.001), SUVmean (median 2.5 vs. 1.5; P <
      0.001), k3 (relative decrease of 52%; P = 0.002), Ki (relative decrease of 27%; P
      = 0.03), whereas there was an increase in k4 (+367%; P < 0.001). CONCLUSIONS:
      Hybrid 18 F-FDG-PET/CTP allowed the response of NSCLC to SABR to be assessed
      regarding metabolic and functional parameters. Future studies are needed, with
      correlation with long-term outcomes, to evaluate these findings as potential
      imaging biomarkers of response.

PMID- 30281920
TI  - Clinical effectiveness and safety of antazoline-based therapy in patients with
      stable coronary artery disease undergoing pharmacological cardioversion of short
      duration atrial fibrillation in the emergency department.
AB  - INTRODUCTION: Options for a pharmacological cardioversion (CV) of short-duration
      atrial fibrillation (AF) in patients with a stable coronary artery disease (CAD)
      are limited to amiodarone or vernakalant. Antazoline has been reported to achieve
      high rates of AF conversion to sinus rhythm, but data on its effectiveness and,
      more importantly, safety in stable CAD patients, have been sparse. AIMS: To
      assess the effectiveness and safety of antazoline-based therapy in patients with
      a stable CAD undergoing pharmacological CV of short-duration AF in the emergency
      department (ED). RESULTS: A retrospective case-control study. We conducted an
      analysis of medical records of patients with a stable CAD undergoing CV of short
      duration (<=48 hours) AF in the ED using intravenous antazoline. The main
      endpoints of the study were successful cardioversion of AF and hospitalization
      due to the adverse effects (AE) of the treatment. Between 2008 and 2012, out of
      548 CVs, antazoline was administered 334 times: 138 in CAD and 196 in the control
      group. Patients in the CAD group were older and had more comorbidities than
      controls; 65 patients had had a history of myocardial infarction (MI). In CAD
      group, the effectiveness was higher (82.6% vs 63.8%, RB: 1.30 [95% CI: 1.14
      1.48], P = 0.0002) and the hospitalization rate due to AE was similar (1.4% vs
      4.1%, RR: 0.36 [95% CI: 0.08-1.65], P = 0.2054) to the control group. Among
      patients with CAD, a history of MI did not influence the effectiveness or safety
      of the CV (P = 0.2252 and P = 1.0000, respectively). CONCLUSIONS: In selected
      patients with a stable CAD, even with a history of MI, antazoline-based CV of
      short-duration AF may be an effective and safe therapeutic option.

PMID- 30281921
TI  - Structural, optical tuning, and mechanical behavior of zirconia toughened alumina
      through europium substitutions.
AB  - The structural and optical features of zirconia toughened alumina (ZTA) due to
      the assorted range of Eu3+ substitutions are demonstrated. The characterization
      studies affirm the pivotal role of Eu3+ on the improved structural stability of
      ZTA and associated tetragonal zirconia (t-ZrO2 ) -> cubic zirconia (c-ZrO2 )
      transformation. Eu3+ prefers accommodation at the lattice sites of ZrO2 and their
      gradual accumulation induces t- -> c-ZrO2 transition. Beyond the substitution
      limit, Eu3+ reacts with Al2 O3 to form EuAlO3 . Optical studies validate typical
      Eu3+ emissions, and further, the emission spectrum also predicts the symmetry of
      Eu3+ coordination at the ZrO2 lattice. Uniform distribution of ZrO2 and Al2 O3
      grains throughout the microstructures are evident from the morphological
      analysis. Further, the influence of Eu3+ on the enhanced mechanical stability of
      ZTA is ensured from indentation technique. (c) 2018 Wiley Periodicals, Inc. J
      Biomed Mater Res B Part B: 2018.

PMID- 30281922
TI  - Evaluation of Sydnone-Based Analogues of Combretastatin A-4 Phosphate (CA4P) as
      Vascular Disrupting Agents for Use in Cancer Therapy.
AB  - The combretastatins have attracted significant interest as small-molecule
      therapies for cancer due to their ability to function as vascular disrupting
      agents. We have successfully prepared a range of combretastatin analogues that
      are based on a novel sydnone heterocycle core, and their potential as tubulin
      binders has been assessed in vitro and in vivo. The most potent candidate was
      found to disrupt microtubules and affect cellular morphology at sub-micromolar
      levels. Moreover, it was found to bind reversibly to tubulin and significantly
      increase endothelial cell monolayer permeability, in a similar manner to
      combretastatin A4. Surprisingly, the compound did not exhibit efficacy in vivo,
      possibly due to rapid metabolism.

PMID- 30281923
TI  - Molecular characterization of two novel atypical porcine pestivirus (APPV)
      strains from piglets with congenital tremor in China.
AB  - As one of emerging porcine viruses, atypical porcine pestivirus (APPV) was found
      in three continents since it emerged in 2015. It is now thought as the causative
      agent for congenital tremor type A-II in piglets. At the end of 2017, two APPV
      strains were identified from piglets with congenital tremor in Guangxi and
      Yunnan, China. The genome of APPV GX04/2017 strain was so far determined to be
      11,534 nucleotides (nt) in length and contains a single open reading frame (ORF)
      encoding a polyprotein comprising 3,635 amino acids. Comparative analysis of ORF,
      Npro , E2, and NS3 gene sequences revealed that the APPV GX04/2017 strain shares
      nucleotide sequence identities of 82.8%-92.8% with other APPV strains, while
      YN01/2017 strain is 79.4%-97.4% homology to the others. Phylogenetic analysis
      showed that the APPV GX04/2017 and YN01/2017 are two novel APPV strains with the
      highest homology to each other, and relative high similarity to the APPV 000515
      and JX-JM01 strains in genome sequence. The current findings provide updated
      information about APPV epidemiology and divergence in China, which would
      certainly help to establish reliable diagnosis and surveillance programs for
      APPV.

PMID- 30281924
TI  - Polymorphisms associated with fentanyl pharmacokinetics, pharmacodynamics and
      adverse effects.
AB  - Fentanyl is an agonist of the MU-opioid receptor commonly used in the treatment
      of moderate-severe pain. In order to study whether pharmacogenetics explains some
      of the variability in the response to fentanyl, several genes related to fentanyl
      receptors, transporters and metabolic enzymes have been analysed. Thirty-five
      healthy volunteers (19 men and 16 women) receiving a single 300 MUg oral dose of
      fentanyl were genotyped for 9 polymorphisms in cytochrome P450 (CYP) enzymes
      (CYP3A4 and CYP3A5), ATP-binding cassette subfamily B member 1 (ABCB1), opioid
      receptor mu 1 (OPRM1), catechol-O-methyltransferase (COMT) and adrenoceptor beta
      2 (ADRB2) by real-time PCR. Fentanyl concentrations were measured by ultra
      performance liquid chromatography combined with tandem mass spectrometry (UPLC
      MS/MS). Fentanyl pharmacokinetics is affected by sex. Carriers of the CYP3A4*22
      allele, which is known to reduce the mRNA expression, showed higher area under
      the concentration-time curve (AUC) and lower clearance (Cl) values. Although this
      finding might be of importance, its validity needs to be confirmed in other
      similar settings. Furthermore, carriers of the ABCB1 C1236T T/T genotype
      presented a lower AUC and higher Cl, as well as lower half-life (T1/2 ). As
      volunteers were blocked with naltrexone, the effect of fentanyl on
      pharmacodynamics might be biased; however, we could observe that fentanyl had a
      hypotensive effect. Moreover, ADRB2 C523A A allele carriers showed a tendency
      towards reducing systolic blood pressure. Likewise, OPRM1 and COMT minor allele
      variants were risk factors for the development of somnolence. CYP3A5*3, ABCB1
      C3435T and ABCB1 G2677T/A were not associated with fentanyl's pharmacokinetics,
      pharmacodynamics and safety profile.

PMID- 30281925
TI  - Pd0 -Catalyzed Four-Component Reaction of Aryl Halide, CO, N-Tosylhydrazone, and
      Amine.
AB  - A Pd0 -catalyzed four-component cascade reaction of an aryl halide, CO, an N
      tosylhydrazone, and an amine affording alpha-amino ketone has been developed.
      This reaction involves a sequential carbonylation, metal carbene migratory
      insertion, and amination. Control experiments and DFT calculations further reveal
      the reaction sequence and chemoselectivity of individual components in this
      cascade process.

PMID- 30281926
TI  - Balloon Eustachian tuboplasty under monitored anaesthesia care with different
      balloon dilation devices: A pilot feasibility study with 18 patients.

PMID- 30281927
TI  - B cell lymphoma-2-like protein-12 association with T-helper 2 inflammation in
      chronic rhinosinusitis with allergy.
AB  - BACKGROUND: T-helper 2 (Th2) polarization plays a critical role in the
      pathogenesis of chronic rhinosinusitis (CRS) with accompanying nasal allergy.
      Recent studies indicate that B cell lymphoma-2-like protein-12 (Bcl2L12) is
      associated with immune dysregulation. The purpose of this study was to elucidate
      the role of Bcl2L12 in the pathogenesis of Th2 polarization of CRS patients.
      METHODS: CRS patients with nasal allergy (CRSa) and without nasal allergy (CRSna)
      were recruited into this study. CD4+ T cells were isolated from the blood samples
      of human subjects. A variety of immunologic molecular strategies were used to
      assess Th2 polarization and Bcl2L12 expression. RESULTS: Twenty CRSa patients, 20
      CRSna patients, and 20 healthy subjects were recruited into this study. High
      levels of immunoglobulin E (IgE), interleukin 4 (IL-4), IL-5, IL-13, and Bcl2L12
      were detected in nasal extracts of CRSa patients, but not in CRSna patients. The
      levels of Bcl2L12 were positively correlated with Th2 cytokines. CD4+ T cells
      from CRSa patients were prone to differentiate into Th2 cells, in which Bcl2L12
      was required. CONCLUSION: Bcl2L12 is positively correlated with Th2 cytokine
      levels in the nasal mucosa of CRSa patients. Bcl2L12 contributes to the Th2
      polarization, which may be a novel therapeutic target in the treatment of CRSa.

PMID- 30281928
TI  - SNOT-22 score patterns strongly negatively predict chronic rhinosinusitis in
      patients with headache.
AB  - BACKGROUND: Differentiating the non-sinogenic headache from chronic
      rhinosinusitis (CRS) remains a significant clinical challenge due to the
      extensive overlap in symptoms. The objective of this study was to evaluate the 22
      item Sino-Nasal Outcome Test (SNOT-22) score patterns in patients with confirmed
      non-sinogenic headache in order to develop negative predictors of CRS. METHODS:
      Institutional Review Board (IRB)-approved, retrospective review of patients
      diagnosed with CRS or non-sinogenic headache defined as patients with a chief
      complaint of headache, facial pain, and facial pressure in the absence of both
      endoscopic and computed tomography (CT) evidence of inflammation. The optimal
      cutoff points of potential predictors of non-sinogenic headache by SNOT-22 score
      were quantified by receiver operating characteristic (ROC) curve. The negative
      predictive values (NPVs) for CRS were calculated in a discovery population and
      then validated in an independent population. RESULTS: A total of 724 (164 non
      sinogenic headache and 560 CRS) and 412 (88 non-sinogenic headache and 324 CRS)
      patients were recruited in the discovery and validation populations,
      respectively. Domain 3 (Ear/facial) and domain 4 (Psychological dysfunction) were
      significantly higher in patients with non-sinogenic headache as compared with CRS
      while domain 1 (Rhinologic) and domain 2 (Extranasal rhinologic) were
      significantly lower. The top 4 predictors of non-sinogenic headache were the
      domain 3 (Ear/facial)/domain 1 (Rhinologic) ratio, item 12, domain 3
      (Ear/facial), and (item 12 + item 10)/(item 4 + item 5) ratio, with areas under
      the ROC curve (AUCs) ranging from 0.637 to 0.720 by ROC curve. A domain 3
      (Ear/facial)/domain 1 (Rhinologic) ratio over 0.66 performed as the best negative
      predictor of CRS with the highest NPVs of 0.880 and 0.889 in the discovery and
      validation populations, respectively. CONCLUSION: Patients with non-sinogenic
      headache have distinct SNOT-22 score patterns compared with patients with CRS. A
      domain 3 (Ear/facial)/domain 1 (Rhinologic) ratio greater than 0.66 is a strong
      negative predictor of CRS, which can be used to aid in patient counseling and
      potentially limit the use of unnecessary sinonasal therapeutics.

PMID- 30281929
TI  - 14-3-3 protein masks the nuclear localization sequence of caspase-2.
AB  - Caspase-2 is an apical protease responsible for the proteolysis of cellular
      substrates directly involved in mediating apoptotic signaling cascades. Caspase-2
      activation is inhibited by phosphorylation followed by binding to the scaffolding
      protein 14-3-3, which recognizes two phosphoserines located in the linker between
      the caspase recruitment domain and the p19 domains of the caspase-2 zymogen.
      However, the structural details of this interaction and the exact role of 14-3-3
      in the regulation of caspase-2 activation remain unclear. Moreover, the caspase-2
      region with both 14-3-3-binding motifs also contains the nuclear localization
      sequence (NLS), thus suggesting that 14-3-3 binding may regulate the subcellular
      localization of caspase-2. Here, we report a structural analysis of the 14-3
      3zeta:caspase-2 complex using a combined approach based on small angle X-ray
      scattering, NMR, chemical cross-linking, and fluorescence spectroscopy. The
      structural model proposed in this study suggests that phosphorylated caspase-2
      and 14-3-3zeta form a compact and rigid complex in which the p19 and the p12
      domains of caspase-2 are positioned within the central channel of the 14-3-3
      dimer and stabilized through interactions with the C-terminal helices of both 14
      3-3zeta protomers. In this conformation, the surface of the p12 domain, which is
      involved in caspase-2 activation by dimerization, is sterically occluded by the
      14-3-3 dimer, thereby likely preventing caspase-2 activation. In addition, 14-3-3
      protein binding to caspase-2 masks its NLS. Therefore, our results suggest that
      14-3-3 protein binding to caspase-2 may play a key role in regulating caspase-2
      activation. DATABASE: The atomic coordinates and structure factors have been
      deposited in the Protein Data Bank, www.ww pdb.org (PDB ID codes 6GKF and 6GKG).

PMID- 30281930
TI  - Impact of chronic rhinosinusitis on sleep: a controlled clinical study.
AB  - BACKGROUND: Earlier studies have suggested that patients with chronic
      rhinosinusitis (CRS) report worse sleep quality than population norms. What
      remains unknown is whether these patients are actually experiencing measurable
      changes in objective sleep parameters. The goal of this study was to
      prospectively evaluate objective sleep measures in a cohort of patients with CRS.
      METHODS: A prospective, multi-institutional, case-control study was designed to
      compare patients with CRS to nondiseased controls. Sleep quality was measured
      using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale
      (EpSS). Home sleep studies were administered across all subjects and a battery of
      objective sleep measurements were recorded using a portable sleep diagnostic
      device. Regression models were used to control for any factors that differed
      across groups. RESULTS: A total of 108 subjects were enrolled across 4
      institutions, including 52 patients with CRS and 56 controls. Total PSQI scores
      were worse in patients with CRS when compared with controls (10.1 +/- 4.3 vs 4.7
      +/- 2.5; p < 0.001). Similarly, daytime somnolence, as measured by the EpSS, was
      greater in patients with CRS (9.1 +/- 5.3 vs 6.5 +/- 3.7; p = 0.006). On home
      sleep studies, patients with CRS were found to have an increased number of
      awakenings during a night's sleep (8.6 +/- 4.8 vs 6.3 +/- 3.0; p = 0.004), lower
      average overnight oxygen saturation (93.2 +/- 2.6% vs 94.3 +/- 2.1%; p = 0.042),
      increased rapid eye movement sleep (REMS) latency (93.0 +/- 67.1 vs 66.7 +/-
      35.3; p = 0.016), and spent a greater portion of the night snoring at >40 dB
      (24.7 +/- 27.4% vs 14.6 +/- 19.7%; p = 0.034). All differences except mean oxygen
      saturation remained significant after controlling for baseline differences.
      CONCLUSION: Differences in both patient-reported and objective sleep measures
      exist between patients with CRS and controls.

PMID- 30281931
TI  - Inhibition of isoprenylation synergizes with MAPK blockade to prevent growth in
      treatment-resistant melanoma, colorectal, and lung cancer.
AB  - This study evaluates the use of HMG-CoA reductase inhibitors, or statins, as an
      adjunctive to BRAF and MEK inhibition as a treatment in melanomas and other
      tumors with driver mutations in the MAPK pathway. Experiments used simvastatin in
      conjunction with vemurafenib and selumetinib in vitro and simvastatin with
      vemurafenib in vivo to demonstrate additional growth abrogation beyond MAPK
      blockade alone. Additional studies demonstrated that statin anti-tumor effects
      appeared to depend on inhibition of isoprenoid synthesis given rescue with add
      back of downstream metabolites. Ultimately, we concluded that statins represent a
      possible useful adjunctive therapy in MAPK-driven tumors when given with current
      approved targeted therapy.

PMID- 30281932
TI  - Genetic Engineering of Human Pluripotent Stem Cells Using PiggyBac Transposon
      System.
AB  - Human pluripotent stem cells (hPSCs) emerged as an important tool to investigate
      human development and disease. These studies often require genetically
      engineering hPSCs to stably express a transgene, which remains functional in
      various hPSC progeny. PiggyBac transposon is a highly effective and technically
      simple vector system with large cargo space available for permanent gene
      delivery. This unit describes the use of PiggyBac transposons to genetically
      engineer hPSCs to introduce conditionally expressed transgene or reporter to
      effectively monitor gene expression during differentiation. Both methods enable
      robust generation of stable hPSC lines within 1 month. (c) 2018 by John Wiley &
      Sons, Inc.

PMID- 30281933
TI  - Deletion of Nrf2 enhances susceptibility to eosinophilic sinonasal inflammation
      in a murine model of rhinosinusitis.
AB  - BACKGROUND: Oxidative stress exacerbates lower airway diseases including asthma
      and chronic obstructive pulmonary disease (COPD); however, its role in upper
      airway (sinonasal) chronic inflammatory disorders is less clear. Nuclear
      erythroid 2 p45-related factor (Nrf2) is an endogenous mechanism that upon
      activation invokes an antioxidant response pathway via nuclear translocation and
      upregulation of cytoprotective genes. We sought to determine whether deletion of
      Nrf2 enhances susceptibility to allergic sinonasal inflammation in vivo. METHODS:
      Nrf2-/- mice were subjected to the ovalbumin (Ova)-induced murine model of
      rhinosinusitis and indices of sinonasal inflammation and epithelial barrier
      dysfunction were assessed. RESULTS: We show that deletion of Nrf2 results in
      enhances indices of allergen-induced sinonasal inflammation including aggravated
      eosinophil accumulation and goblet cell hyperplasia. An exaggerated increase in
      epithelial derived inflammatory cytokines including interleukin 33 (IL-33) and
      thymic stromal lymphopoietin (TSLP) was observed in the nasal lavage fluid and
      sinonasal mucosal tissue of Nrf2-/- mice. Furthermore, Nrf2-/- mice showed
      heightened Ova-induced barrier dysfunction as measured by serum albumin
      accumulation in nasal lavage fluid of mice. CONCLUSION: These data show that the
      endogenous Nrf2 pathway limits Ova-induced sinonasal inflammation, epithelial
      derived inflammatory cytokine production, and epithelial barrier dysfunction in
      vivo and identify a potential therapeutic target in the management of allergic
      sinonasal inflammatory disorders. This is the first study to our knowledge which
      shows that Nrf2 regulates allergic inflammation in the sinonasal cavity in vivo.

PMID- 30281935
TI  - Translational research: Empowering the role of pathologists and cytopathologists.
AB  - Research activity is in the core essence of pathology. Advancing our
      understanding of disease pathogenesis translates into better patient care.
      Because of their unique position, laboratorians are the best to accurately
      identify, annotate, and classify research specimens. They also are essential for
      the accurate interpretation of genomic testing. Currently, cytopathologists are
      moving to the center of patient care through active communication with clinicians
      and patients. There are certain research areas in which cytopathologists can be
      pioneers, such as image analysis, morphology research, and genotype-phenotype
      association studies integrating morphologic and molecular features. Health
      service utilization research is another domain in which cytopathologists can
      excel. Successful research is a journey that necessitates multiple steps. It also
      involves building expertise in how to overcome obstacles and handle challenges.

PMID- 30281934
TI  - Compromising Between Phase Stability and Electrical Performance: SrVO3 -SrTiO3
      Solid Solutions as Solid Oxide Fuel Cell Anode Components.
AB  - The applicability of perovskite-type SrVO3-delta in high-temperature
      electrochemical energy conversion technology is hampered by the limited stability
      domain of the perovskite phase. The aim of the present work was to find a
      compromise between the phase stability and electrical performance by designing
      solid solutions in the SrVO3 -SrTiO3 system. Increasing titanium content in SrV1
      y Tiy O3-delta (y=0-0.9) perovskites is demonstrated to result in a gradual shift
      of the upper-p(O2 ) phase stability boundary toward oxidizing conditions: from
      ~10-15  bar at 900  degrees C for undoped SrVO3-delta to ~10-11 -10-5  bar for
      y=0.3-0.5. Although the improvement in the phase stability is accompanied by a
      decrease in electrical conductivity, the conductivities of SrV0.7 Ti0.3 O3-delta
      and SrV0.5 Ti0.5 O3-delta at 900  degrees C remain as high as 80 and 20 S cm-1 ,
      respectively, and is essentially independent of p(O2 ) within the phase-stability
      domain. Combined XRD, thermogravimetric analysis, and electrical studies revealed
      very sluggish kinetics of oxidation of SrV0.5 Ti0.5 O3-delta ceramics under inert
      gas conditions and a nearly reversible behavior after exposure to an inert
      atmosphere at elevated temperatures. Substitution by titanium in the SrV1-y Tiy
      O3-delta system results also in a decrease of oxygen deficiency in perovskite
      lattice and a favorable suppression of thermochemical expansion. Variations of
      oxygen nonstoichiometry and electrical properties in the SrV1-y Tiy O3-delta
      series are discussed in combination with the simulated defect chemistry of solid
      solutions.

PMID- 30281936
TI  - Analysis of Cysteine Post Translational Modifications Using Organic Mercury
      Resin.
AB  - The wide reactivity of the thiol group enables the formation of a variety of
      reversible, covalent modifications on cysteine residues. S-nitrosylation, like
      many other post-translational modifications, is site selective, reversible, and
      necessary for a wide variety of fundamental cellular processes. The overall
      abundance of S-nitrosylated proteins and reactivity of the nitrosyl group
      necessitates an enrichment strategy for accurate detection with adequate depth.
      Herein, a method is presented for the enrichment and detection of endogenous
      protein S-nitrosylation from complex mixtures of cell or tissue lysate utilizing
      organomercury resin. Minimal adaptations to the method also support the detection
      of either S-glutathionylation or S-acylation using the same enrichment platform.
      When coupled with high accuracy mass spectrometry, these methods enable a site
      specific level of analysis, facilitating the curation comparable datasets of
      three separate cysteine post-translational modifications. (c) 2018 by John Wiley
      & Sons, Inc.

PMID- 30281937
TI  - Numerical evaluation of nonbonded piezo sensor for biomedical diagnostics using
      electromechanical impedance technique.
AB  - Directly bonded piezo sensor, conventionally employed in the electromechanical
      impedance (EMI) technique, although a proven candidate for structural health
      monitoring, is severely constrained in its application in the biomedical field
      due to its bonding requirement. In contrast, nonbonded piezo sensor (NBPS)
      provides a viable platform to assess the condition of human bones, tissues, and
      other biomedical subjects using the EMI technique without inflicting pain or
      irritation to the skin. The name NBPS was coined to emphasize that there was no
      direct bonding between the PZT patch and the live subject; instead, the PZT patch
      was bonded to a supporting medium, which maintains the mechanical interaction
      between the PZT patch and the subject. However, there are several aspects in the
      analysis of NBPS configuration that cannot be addressed completely through
      experimental study due to measurement constraints, cost, and time. For example,
      experimentally changing the density of bone continuously to study the
      osteoporosis effect is a tedious task warranting large number of specimens. This
      paper presents a detailed parametric study based on finite element method
      covering condition monitoring of human bones using the NBPS configuration. It is
      for the first time that 3D analysis for specimen identification and damage
      detection in bones using NBPS has been carried out. In addition to the validation
      of the numerical model against the previously established experimental studies
      involving bones, quantification of the extent of damage and its localization has
      been investigated. The density changes due to osteoporosis in bones are
      comprehensively investigated by the NBPS including the quantification aspect of
      osteoporosis/damage. Definite acquisition of bone signature and detection of
      physiological changes in bones are achieved even with the presence of skin,
      muscle, and fat layers on the bone.

PMID- 30281938
TI  - Management and outcome of epistaxis under direct oral anticoagulants: a
      comparison with warfarin.
AB  - BACKGROUND: Epistaxis is one of the more common reasons for emergency room
      visits. The main risk factor for epistaxis is anticoagulant therapy. Until
      recently, the main culprit was oral intake of a vitamin K antagonist, such as
      warfarin, which has a number of side effects. Even more recently, several direct
      oral anticoagulants, rivaroxaban and dabigatran, have been approved for use. We
      investigated the possible differences between treatment of epistaxis with direct
      oral anticoagulants and vitamin K antagonists. METHODS: We conducted a
      retrospective cohort study at a tertiary referral center in Germany. All patients
      who were admitted within a 1-year period were included. Patient files were used
      to obtain the information. RESULTS: Overall, 677 patients were included in our
      study. Of these, 159 had been treated with vitamin K antagonists and 49 with
      direct oral anticoagulants. There were no significant differences in terms of age
      (p = 0.592), sex (p = 0.372), vital signs, bloodwork, or location of bleeding (p
      = 0.372). Management of epistaxis between the groups was also comparable (p =
      0.399), with similar hospital admission rates (37.1% vs 24.5%; p = 0.145) and
      duration of stay (3.5 +/- 2.1 days vs 3.8 +/- 3.3 days; p = 0.650). CONCLUSION:
      We found no evidence to suggest epistaxis is more severe or requires more
      invasive therapy in patients given direct oral anticoagulants. A significant
      proportion of patients on vitamin K antagonists were not within the target range
      for international normalized ratio, highlighting one of the main issues with oral
      anticoagulation by vitamin K antagonists.

PMID- 30281939
TI  - Deficiency in interleukin-10 production by M2 macrophages in eosinophilic chronic
      rhinosinusitis with nasal polyps.
AB  - BACKGROUND: M2 macrophages are characterized by high interleukin-10 (IL-10)
      expression and are critical for resolving inflammation. Although increased
      accumulation of M2 macrophages has been demonstrated in chronic rhinosinusitis
      with nasal polyps (CRSwNP), particularly the eosinophilic type, their functional
      relevance in CRSwNP remains poorly understood. METHODS: M1 and M2 macrophages and
      IL-10 expression in sinonasal tissues were detected by double-immunofluorescence
      staining. THP-1 cells, a human monocytic leukemia cell line, were stimulated with
      various cytokines to study macrophage polarization and IL-10 expression. Polyp
      size, computed tomography (CT) scans, and symptom severity were scored. RESULTS:
      Compared with numbers in control tissues, the numbers of total CD68+ macrophages,
      interferon regulatory factor 5-positive and CD68+ M1 macrophages, and CD163+
      CD68+ and CD206+ CD68+ M2 macrophages were increased in both eosinophilic and non
      eosinophilic polyps. However, compared with non-eosinophilic polyps, eosinophilic
      polyps contained fewer M1 macrophages and more M2 macrophages. Consistent with
      this, the M1/M2 macrophage ratio was increased in non-eosinophilic polyps,
      whereas it decreased in eosinophilic polyps. Strikingly, the numbers of IL-10+
      CD68+ macrophages and the percentage of IL-10+ CD68+ macrophages relative to the
      total number of macrophages were decreased in eosinophilic polyps, despite the
      upregulation of M2 macrophages in this type of polyp. The number of IL-10+ CD68+
      M2 macrophages correlated negatively with total symptoms scores, polyp sizes,
      total CT scores, and the total number of inflammatory cells in patients with
      eosinophilic CRSwNP. Poly I:C downregulated IL-10 expression in M2 macrophages
      differentiated from THP-1 cells in vitro. CONCLUSION: Impaired IL-10 production
      by M2 macrophages may contribute to sustained inflammation in eosinophilic
      CRSwNP.vv.

PMID- 30281940
TI  - Retrospective detection of Brachyspira hampsonii in archived colitis cases from
      western Canadian swine.
AB  - Mucohaemorrhagic diarrhea associated with Brachyspira hampsonii infection has
      emerged as a production-limiting disease in western Canada. This pathogen was
      first described in North America in 2010, and reports of its detection occurred
      concurrently in western Canada and the United States. Since that time,
      Brachyspira hampsonii has been detected in Europe, both in pigs and in waterfowl.
      The origin of B. hampsonii and the timing and reasons for its emergence are
      unknown. We conducted a retrospective study of historic, archived cases of
      porcine colitis to determine when B. hampsonii was first evident in western
      Canada. A total of 206 samples from 114 cases submitted from 57 different farms
      or productions systems in 1984 and 1999-2009 were screened using real-time PCR
      assays targeting B. hampsonii genomovars I and II, and Brachyspira hyodysenteriae
      (the traditional agent of swine dysentery). In most cases, positive real-time PCR
      results were confirmed by amplification and sequencing of additional gene
      targets. A total of 9, 7 and 5 samples tested positive for B. hampsonii (I), B.
      hampsonii (II) or B. hyodysenteriae respectively. The results of this study push
      the date of first appearance of B. hampsonii in pigs in western Canada back to
      2002 (B. hampsonii (I)) and 2006 (B. hampsonii (II)), which is up to 7 years
      before the new species were first identified in fresh samples.

PMID- 30281941
TI  - Effects of mometasone furoate-impregnated biodegradable nasal dressing on
      endoscopic appearance in healing process following endoscopic sinus surgery: a
      randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Postoperative care is an important factor affecting the outcome of
      endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). The
      aim of this study was to test the effect of mometasone furoate (MF)-soaked
      biodegradable nasal dressings (BNDs) on endoscopic appearance in CRS patients
      with nasal polyps (CRSwNP) after ESS. METHODS: This study was a prospective,
      randomized, double-blinded, placebo-controlled study. A total of 64 CRSwNP
      patients with bilateral ESS were enrolled and randomly given 4 mL or 8 mL of MF
      soaked BNDs (NasoPore) in 1 nasal cavity and the same amount of normal saline
      soaked BNDs in the contralateral side. The BNDs were removed on the 7th or 14th
      postoperative day. Perioperative sinus endoscopy (POSE) and Lund-Kennedy scores
      were collected, on the 7th or 14th postoperative days and at 1, 2, and 3
      postoperative months. RESULTS: The POSE and Lund-Kennedy scores showed that in
      the 4-mL, 1-week group, no significant differences between the sides treated with
      MF-soaked BNDs and the normal saline-soaked control were observed at any
      postoperative visits. In the 4-mL, 2-week group, significant differences were
      found at the 2-week and 1-month postoperative visits but not at the 2-month and 3
      month visits. In the 8-mL, 1-week group, significant differences were found at
      the 1-week, 1-month, and 2-month postoperative visits but not at the 3-month
      visit. In the 8-mL, 2-week group, significant differences were found at all
      postoperative visits. CONCLUSION: This study reveals that MF-impregnated BNDs
      improve the endoscopic appearance in the healing process of CRSwNP after ESS.

PMID- 30281942
TI  - Effectiveness and cost-benefit study to encourage herd owners in a cost sharing
      vaccination programme against bluetongue serotype-8 in Belgium.
AB  - Bluetongue (BT) is a ruminant viral infectious disease transmitted by Culicoides
      spp. midges. In 2006, when bluetongue virus serotype 8 (BTV-8) appeared for the
      first time in Northern Europe, it rapidly spread and infected a large proportion
      of animals. BThas a significant economic impact due to a direct effect on animal
      health and to an indirect effect in disrupting international trade of animals and
      animal products. In spring 2008, a compulsory subsidized vaccination programme in
      Europe resulted in a drastic decrease in the number of reported cases. However,
      due to the turn-over of the population, without a continuous vaccination
      programme, the animal population was becoming progressively susceptible.
      Vaccination would enable Belgium to maintain its status of freedom from infection
      of BTV-8 that could possibly be re-introduced. Subsidizing it could be an
      incentive to convince more farmers to vaccinate. To finance this programme, both
      decision-makers and stakeholders need to be persuaded by the effectiveness and
      the cost-benefit of vaccination. The study evaluated the effectiveness of
      vaccination against BTV-8 in Belgium. The change in serology which has shown the
      effectiveness of the vaccine to induce antibody production has been significantly
      associated with the time between the first injection and the sampling date and
      the number of injections of the primo-vaccination. This study also clearly
      confirms the benefit of vaccination by reducing economic impact of treatment and
      production losses, especially in dairy cattle. Based on a participating
      epidemiological approach, a national voluntary and subsidized vaccination was
      accepted, and permitted Belgium to vaccinate more than 9,000 herds in 1 month.
      Because this mass vaccination occurred before the vector season, it probably
      helped Belgium remain free from BTV-8.

PMID- 30281943
TI  - Establishment of a CFD-based kL a model in microtiter plates to support CHO cell
      culture scale-up during clone selection.
AB  - Microtiter plates are a common tool for clone selection in biopharmaceutical
      development. A way of visualizing and evaluating these systems and key processes
      parameters is the application of Computational Fluid Dynamics (CFD). CFD is a
      powerful tool for the modelling of hydrodynamics and mass transfer parameters. In
      this work, CFD was used to determine the specific surface area, the volumetric
      power input and the oxygen mass transfer coefficient kL a for two different
      microtiter plates with different scales (100 MUL - 5 mL). For this purpose, a new
      method of predicting the kL a is presented and calibrated with literature data.
      Scaling effects in shaken microtiter plates are evaluated by comparing two
      culture volume scales under various operating conditions. To test validity of
      these models, three different Boehringer Ingelheim Pharma proprietary CHO
      production cell lines with different growth characteristics were cultivated using
      the respective microtiter plates under different conditions until limitations in
      growth and viability were observable. The cell culture data then was compared to
      different parameters obtained by CFD. The calculated kL a values match the cell
      culture performance in the 96-deepwell by predicting lowered oxygen transfer with
      increasing culture volume and decreasing orbital velocity. The same cells behave
      differently in the 6-deepwell scale. Here, the overall larger shear stress might
      cause physical stress for the cells. The kL a model predicts overall higher shear
      rates for this system, supporting the experimental findings. (c) 2018 American
      Institute of Chemical Engineers Biotechnol. Prog., 2018.

PMID- 30281944
TI  - Genetic diversity of Leishmania tropica in Morocco: does the dominance of one
      haplotype signify its fitness in both predominantly anthropophilic Phlebotomus
      sergenti and human beings?
AB  - In Morocco, cutaneous leishmaniasis (CL) caused by Leishmania tropica is endemic
      to locations where the predominantly anthropophilic blood-feeding Phlebotomus
      sergenti and humans co-perpetuate. The objective of this study was to explore
      whether the range of epidemiological features of CLcould be linked to the range
      of L. tropica genetic heterogeneity and to further explore the relationships
      between the genetic diversity of L. tropica in both P. sergenti and humans. L.
      tropica DNAwas extracted from dermal scarping smears of 125 CLpatients. Genetic
      polymorphisms were analyzed by sequencing the internal transcribed spacer (ITS) 1
      and 5.8S rDNAgene. Nucleotide diversity (pi), haplotype diversity (Hd) and
      Tajima's D test for neutrality, as well as overall and pairwise FSTvalues, were
      calculated using Arlequin ver 3.5 software. Out of the 125 amplified
      DNAsequences, 93 were completely sequenced and 13 L. tropica haplotypes were
      identified, which confirmed the significant genetic heterogeneity of L. tropica
      in Morocco. The most common haplotype included 74 out of 93 sequences; this
      haplotype is not only widely represented but was also detected in P. sergenti,
      which is known to be the most abundant species in the studied foci. Considering
      the negative value calculated using Tajima's D index, we briefly discussed the
      hypothesis that the L. tropica common haplotype propagation could be a sign of
      its fitness in P. sergenti and human hosts. Furthermore, analysis of molecular
      variance (AMOVA) shows significant correlations between intraspecific variants of
      L. tropica and patients' geographic origins. The long-term goals of the present
      pilot study are to further explore the relationships between the genetic
      diversity of L. tropica in human and P. sergenti populations.

PMID- 30281945
TI  - Allergic rhinitis and the associated risk of nocturnal enuresis in children: a
      population-based cohort study.
AB  - BACKGROUND: Despite controversy, an association between allergy and nocturnal
      enuresis (NE) has been reported for almost a century. Allergic rhinitis (AR)
      associated sleep-disordered breathing frequently results in microarousals during
      sleep, decreased sleep efficiency, and change in sleep pattern and behavior. NE
      is a common sleep disorder in children. Hence, this study aimed to investigate
      the incidence and risk of NE in children with AR. METHODS: A population-based
      cohort study was conducted among 327,928 children with AR and 327,601 non-AR
      controls between 2000 and 2012 in Taiwan. By the end of 2012, the incidence of NE
      in both cohorts, and the AR-to-non-AR cohort hazard ratios (HRs) were measured.
      RESULTS: The adjusted HR of NE during the study period was 1.7-fold higher in the
      AR cohort compared to the non-AR cohort. The risk was greater for boys, children
      younger than 6 years old, those with comorbidities of asthma, atopic dermatitis,
      and attention deficit/hyperactivity disorder (ADHD), and those who had more than
      5 AR-related medical visits per year. The risk of NE in the AR cohort decreased
      with follow-up time and was the highest within the first year after AR diagnosis.
      CONCLUSION: Children with AR had a higher incidence and subsequent risk of NE.
      The risk of NE was greater for boys, younger children, and those with more
      frequent health utilization for AR symptoms.

PMID- 30281946
TI  - Resting cells isobutanol production by Shimwellia blattae (p424IbPSO): Influence
      of growth culture conditions.
AB  - Isobutanol is a promising gasoline additive and could even be a potential
      substitute used directly as combustible. In this work, the production of
      isobutanol from glucose by Shimwellia blattae (p424IbPSO) in resting cell
      cultures is studied. This production has two stages, involving a resting cell
      phase that has not been studied before. The cell growth was carried out under
      different operating conditions: temperature and medium composition (YE, ammonium,
      and IPTG concentrations), looking for the highest isobutanol production.
      Moreover, the cells were collected at three different growth times checking their
      isobutanol production capacity. The best operating conditions have been
      determined as: 30 degrees C of temperature, a medium containing 1.5 g L-1 YE and
      1.4 g L-1 of ammonium as nitrogen sources, adding 0.5 mM IPTG as inducer. The
      cells collected at early growth times are significantly more active. The use of
      S. blattae (p424IbPSO) in resting cells is a good strategy for the production of
      isobutanol from glucose yielding better results than in batch growth cultures, a
      yield of 60% attainment of theoretical maximum yield is obtained under optimal
      conditions. In addition, it has been demonstrated that if the cells are cultured
      at higher temperatures and with high IPTG concentrations, inclusion bodies are
      formed in the cytoplasm inhibiting the isobutanol production in the resting cell
      stage.

PMID- 30281947
TI  - Glucose Monitoring and Adaptive Feeding of Mammalian Cell Culture in the Presence
      of Strong Autofluorescence by near Infrared Raman Spectroscopy.
AB  - Raman spectroscopy offers an attractive platform for real-time monitoring and
      control of metabolites and feeds in cell culture processes, including mammalian
      cell culture for biopharmaceutical production. However, specific cell culture
      processes may generate substantial concentrations of chemical species and
      byproducts with high levels of autofluorescence when excited with the standard
      785 nm wavelength. Shifting excitation further toward the near-infrared allows
      reduction or elimination of process autofluorescence. We demonstrate such a
      reduction in a highly autofluorescent mammalian cell culture process. Using the
      Kaiser RXN2-1000 platform, which utilizes excitation at 993 nm, we developed
      multivariate glucose models in a cell culture process which was previously
      impossible using 785 nm excitation. Additionally, the glucose level in the
      production bioreactor was controlled entirely by Raman adaptive feeding, allowing
      for maintenance of glucose levels at an arbitrary set point for the duration of
      the culture.

PMID- 30281948
TI  - Separation of alpha-ketoglutaric acid and pyruvic acid from the culture broth of
      Yarrowia lipolytica WSH-Z06 by chromatographic methods.
AB  - Both alpha-ketoglutaric acid (KGA) and pyruvic acid (PYR) are important keto
      acids. Efficient co-production of KGA and PYR has been achieved in our previous
      work, and could significantly decrease the cost of fermentation production. KGA
      and PYR have similar physical and chemical properties. Hence, finding a way to
      separate the two keto acids efficiently has become a key challenge. In this
      study, different chromatographic methods have been investigated, including ion
      exchange chromatography, aluminum oxide chromatography and silica gel
      chromatography. The results show that the two keto acids can be well separated
      with silica gel chromatography, whereas ion-exchange chromatography and aluminum
      oxide chromatography could not separate them. Using the pretreated fermentation
      broth of Yarrowia lipolytica WSH-Z06, the purity and yield of KGA/PYR reached
      98.7%/99.1% and 86.7%/70.9%, respectively, with an optimized silica gel
      chromatography-based procedure. This study provides an efficient method for
      separating KGA and PYR from fermentation broth, which might be applied on an
      industrial scale and significantly decrease the cost of biotechnological
      production of keto acids. (c) 2018 American Institute of Chemical Engineers
      Biotechnol. Prog., 2018.

PMID- 30281949
TI  - High genetic diversity in the Dirofilaria repens species complex revealed by
      mitochondrial genomes of feline microfilaria samples from Narathiwat, Thailand.
AB  - Dirofilaria repens is a zoonotic, mosquito-borne filaria infecting carnivores,
      particularly dogs. It is expanding its range in Europe but epidemiological
      information is sparse for other Eurasian regions. In Hong Kong and India, the
      closely related species Candidatus Dirofilaria hongkongensis was proposed.
      Previous analysis of 2.5 kb partial mitochondrial genome sequences containing the
      particularly variable non-coding control region revealed low diversity in
      European D. repens while Asian nematodes showed high diversity. Sequences derived
      from feline blood samples from Narathiwat (Thailand) led to the proposal of a
      third potential species, Dirofilaria sp. "Thailand II". To avoid bias from
      rapidly evolving non-coding regions, this study aimed to compare Dirofilaria sp.
      "Thailand II" with D. repens and C. D. hongkongensis based on complete
      mitochondrial genomes. Using PCRs and Sanger sequencing, three complete
      mitochondrial genomes (13,651 bp) were assembled from DNA obtained from different
      feline blood samples. Mitochondrial genome organization was identical to other
      onchocercids with eleven protein-coding, two rRNA and 22 tRNA genes and no atp-8
      gene. All genes were on the same strand showing an extremely high thymidine
      content (56.7%). Maximum-likelihood phylogenetic analysis using protein and rRNA
      sequences confirmed closer relationship of Dirofilaria sp. "Thailand II" to C. D.
      hongkongensis than to D. repens. All distances between these three putative
      species were considerably larger than the distance between the valid sibling
      species Onchocerca volvulus and Onchocerca ochengi. Sequencing of a 2.5 kb
      fragment containing the control region from microfilarial DNA from additional
      feline blood samples from Narathiwat 3-4 years later revealed that these also
      fell into the C. D. hongkongensis clade but were remarkably different from C. D.
      hongkongensis and Dirofilaria sp. "Thailand II". Since D. repens-like filaria are
      absent from dogs in Narathiwat, further field studies are required to confirm if
      these genotypes represent locally circulating cat-specific Dirofilaria genotypes
      or species.

PMID- 30281950
TI  - Propagation and Purification of Ectromelia Virus.
AB  - Ectromelia virus (ECTV) is an orthopoxvirus that causes mousepox in mice. Members
      of the genus orthopoxvirus are closely related and include variola (the causative
      agent of smallpox in humans), monkeypox, and vaccinia. Common features of variola
      virus and ECTV further include a restricted host range and similar disease
      progression in their respective hosts. Mousepox makes an excellent small animal
      model for smallpox to investigate pathogenesis, vaccine and antiviral agent
      testing, host-virus interactions, and immune and inflammatory responses. The
      availability of a wide variety of inbred, congenic, and gene-knockout mice allows
      detailed analyses of the host response. ECTV mutant viruses lacking one or more
      genes encoding immunomodulatory proteins are being used in numerous studies in
      conjunction with wild-type or gene-knockout mice to study the functions of these
      genes in host-virus interactions. The methods used for propagation of ECTV in
      cell culture, purification, and quantification of infectious particles through
      viral plaque assay are described. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30281951
TI  - Cell pretreatment with ethylenediaminetetraacetic acid for selective extraction
      of C-phycocyanin with food grade purity.
AB  - C-phycocyanin (C-PC) is a natural blue dye, and depending on its purity, which is
      measured by the ratio between the absorbance of the chromophore (A620 ) and the
      absorbance of the proteins (A280 ), it can be used in food (purity > 0.7),
      cosmetics (purity > 1.5), and therapeutic treatments (purity > 4.0). Several
      physical, chemical, and enzymatic methods of extraction are reported, however,
      few are able to extract C-PC with purity above 0.7. An innovative method of C-PC
      extraction with food grade purity from wet Spirulina platensis biomass is
      proposed. The cells were pretreated with ethylenediaminetetraacetic acid and
      subsequent C-PC extraction was performed with tris-(hydroxymethyl) aminomethane
      SO4 buffer. C-PC was released after 12 h of cell pretreatment. Six variables of
      the extraction process were evaluated. The extraction temperature significantly
      influenced C-PC extraction yield and purity. In the best condition of cell
      pretreatment and extraction, C-PC with purity of 1.0 and extraction yield of
      129.0 mg/g could be obtained to be used as a food dye without any purification
      process. Lastly, an ultrafiltration process was integrated and C-PC was
      concentrated 8.8-fold, resulting in purity of 1.6 and recovery of 93.4%.

PMID- 30281953
TI  - Volatile fatty acids production from protease pretreated Chlorella biomass via
      anaerobic digestion.
AB  - Volatile fatty acids (VFAs) produced via anaerobic digestion (AD) are regarded as
      a low cost production process of building blocks of interest for the chemical
      industry. In this study, VFAs and methane production were assessed in batch
      reactors at different temperature ranges (psychrophilic 25 degrees C, mesophilic
      35 degrees C, thermophilic 50 degrees C) and different pH values (5.5 and 7.5)
      using protease pretreated Chlorella sp. biomass as substrate. Acetic acid and
      propionic acid were the most abundant products (up to 73% of the total VFAs)
      during the first days independently of the conditions. VFAs concentration
      decreased over time as methane was produced after a lag phase of 7-10 days.
      Results showed that best conditions for VFAs production were mesophilic
      temperature ranges (35 degrees C) at neutral initial pH values (7.5), and
      psychrophilic temperature ranges (25 degrees C) at low initial pH values (5.5)
      which resulted in a conversion of the initial COD into VFAs of 48%, respectively.

PMID- 30281952
TI  - Chemically modified alginate bead matrix for efficient adsorptive recovery of
      trypsin from fresh bovine pancreas.
AB  - The adsorption of commercial trypsin (Try) onto epichlorohydrin cross-linked
      alginate-guar gum matrix has been studied at equilibrium in batch and in fixed
      bed column. Experiments were conducted to study the effect of ionic strength,
      temperature and to obtain a thermodynamic characterization of the adsorption
      process. The resulting adsorption isotherm fitted the Hill equation. Experimental
      breakthrough curve profiles were compared with the theoretical breakthrough
      profiles obtained from the mathematical model, bed depth service time. At pH 5.0,
      1.0 g hydrated matrix adsorbed 480.0 milligram of Try per gram of dried bed. The
      desorption process showed 80% of Try recovery in 50 mM phosphate buffer, pH 7.00
      500 mM NaCl-20% propylene glycol. The obtained results were applied to an
      adsorption/washing/desorption process with fresh pancreas homogenate yielded 20%
      of recovery and 5.7 purification factor of Try. The matrix remained functional
      until the fifth cycle of repeated batch enzyme adsorption. (c) 2018 American
      Institute of Chemical Engineers Biotechnol. Prog., 2018.

PMID- 30281954
TI  - Achieving greater efficiency and higher confidence in single-cell cloning by
      combining cell printing and plate imaging technologies.
AB  - In recent years, health authorities have increased emphasis on demonstrating that
      a cell line, which is used for the generation of biologics, is clonally derived.
      Within the past few years, single-cell manipulation technologies, especially
      microfluidic drop-on-demand dispensing, have gained increased attention in the
      biopharmaceutical industry. This work discusses the development and
      characterization of a single-cell printing workflow followed by plate imaging. By
      combining single-cell printing and plate imaging with manual image verification
      it is possible to, (1) dramatically reduce the number of microtiter plates needed
      during the single-cell cloning of clinical cell lines, as compared with a
      limiting-dilution single-cell cloning workflow, and therefore reduce the number
      of high-resolution images acquired and stored and (2) achieve >99.99% assurance
      that the cell lines derived from this workflow are clonally derived.

PMID- 30281955
TI  - Liquid lipase-catalyzed hydrolysis of gac oil for fatty acid production:
      Optimization using response surface methodology.
AB  - Fatty acids are valuable products because they have wide industrial applications
      in the manufacture of detergents, cosmetics, food, and various biomedical
      applications. In enzyme-catalyzed hydrolysis, the use of immobilized lipase
      results in high production cost. To address this problem, Eversa Transform
      lipase, a new and low-cost liquid lipase formulation, was used for the first time
      in oil hydrolysis with gac oil as a triglyceride source in this study. Response
      surface methodology was employed to optimize the reaction conditions and
      establish a reliable mathematical model for predicting hydrolysis yield. A
      maximal yield of 94.16% was obtained at a water-to-oil molar ratio of 12.79:1,
      reaction temperature of 38.9  degrees C, enzyme loading of 13.88%, and reaction
      time of 8.41 h. Under this optimal reaction condition, Eversa Transform lipase
      could be reused for up to eight cycles without significant loss in enzyme
      activity. This study indicates that the use of liquid Eversa Transform lipase in
      enzyme-catalyzed oil hydrolysis could be a promising and cheap method of fatty
      acid production. (c) 2018 American Institute of Chemical Engineers Biotechnol.
      Prog., 2018.

PMID- 30281956
TI  - Unsupervised cluster analysis of chronic rhinosinusitis with nasal polyp using
      routinely available clinical markers and its implication in treatment outcomes.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a
      multidimensional disease. In this study, we performed an unsupervised cluster
      analysis of CRSwNP using routinely available clinical markers. METHODS: We
      conducted a retrospective review of patients treated with endoscopic sinus
      surgery due to medically intractable bilateral CRSwNP from 2009 to 2017.
      Unsupervised cluster analysis was performed using a patient's clinical features,
      including age, peripheral blood eosinophil, tissue eosinophilia, Lund-Mackay
      computed tomography (CT) scores, ratio of the CT scores for the ethmoid sinus and
      maxillary sinus (E/M ratio), and comorbid asthma. Tree analysis was performed to
      develop a clustering algorithm. Kaplan-Meier survival analysis was performed to
      determine the revision surgery-free probability corresponding to each cluster.
      RESULTS: Data were available on 375 patients. Patients were categorized into 6
      clusters comprising 2 asthmatic clusters and 4 non-asthmatic clusters. The labels
      for the 2 asthmatic clusters were: asthmatic non-eosinophilic polyp (cluster A1)
      and asthmatic eosinophilic polyp (cluster A2). The labels for the 4 non-asthmatic
      clusters were: non-eosinophilic polyp with older age (cluster NA1); non
      eosinophilic pol'yp with younger age (cluster NA2); eosinophilic polyp with lower
      E/M ratio (cluster NA3); and eosinophilic polyp with higher E/M ratio (cluster
      NA4). The 4-year revision-free rates were 100% (cluster NA1), 80.3% (NA2), 98.0%
      (NA3), 66.7% (NA4), 100% (A1), and 66.7% (A2). The clusters showed statistically
      significant differences in terms of 4-year revision-free rates (log-rank p <
      0.05). CONCLUSION: Cluster analysis identified 2 asthmatic clusters and 4 non
      asthmatic clusters in CRSwNP. Each cluster corresponded to a different clinical
      outcome.

PMID- 30281957
TI  - The effect of feed quality due to clarification strategy on the design and
      performance of protein A periodic counter-current chromatography.
AB  - The impact of two different quality feeds, derived using two different harvest
      clarification processes, on protein A periodic counter-current chromatography
      (PCC) design and performance is investigated. Data from batch experiments were
      input into a model to design optimal PCC operating parameters specific to each
      feed material. The two clarification methods were: depth filtration using a
      wetlaid matrix which has Q-functionality; and a combination of depth filtration
      and chromatographic clarification, using a Q-functional nonwoven with a high
      anion exchange capacity (EmphazeTM AEX Hybrid Purifier) in which key impurities
      such as host cell DNA (HCDNA) and host cell proteins (HCP) are removed. The model
      predicted 34% better productivity for the chromatographically clarified cell
      culture fluid (CCCF) using a 4 column system, and productivity gains of 28% using
      only 3 columns enabling the option to simplify the protein A PCC strategy.
      Experimental validation of the predicted optimized PCC operating parameters using
      industrially relevant monoclonal antibody (mAb) CCCF feedstock over 100 cycles
      showed productivity gains of 49% for the chromatographically clarified material.
      HCP concentration was 11-fold lower, and HCDNA concentration was reduced by 4.4
      Log Reduction Value (LRV) in the protein A PCC eluates. This work, therefore,
      demonstrates that the removal of HCDNA and HCP during clarification is an
      effective strategy for improving protein A PCC performance. This was achieved
      using the EmphazeTM AEX Hybrid Purifier which can be easily incorporated into a
      batch or continuous process, in a scalable fashion, without adding additional
      separate unit operations. (c) 2018 American Institute of Chemical Engineers
      Biotechnol. Prog., 2018.

PMID- 30281958
TI  - Lipase-catalyzed hydrolysis of (R,S)-2,3-diphenylpropionic methyl ester enhanced
      by hydroxypropyl-beta-cyclodextrin.
AB  - The enantioselective hydrolysis of (R,S)-2,3-diphenylpropionic methyl ester
      ((R,S)-2,3-2-PPAME) catalyzed by lipase to (R)-2,3-diphenylpropionic acid ((R)
      2,3-2-PPA) was studied in an aqueous system. The catalytic effects of different
      types of lipase were compared, and Candida antarctica lipase A (CALA) with higher
      catalytic activity and enantioselectivity was selected. Hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) was added to the aqueous system to increase the
      solubility of 2,3-2-PPAME, which resulted in an increase of 35.56% in substrate
      conversion remaining the high enantiomeric excess. The factors influencing the
      substrate conversion and the optical purity of product such as temperature, pH,
      concentrations of CALA and HP-beta-CD, substrate loading, and reaction time were
      optimized. The optimal conditions for this reaction were obtained, including pH
      of 5.5, 30 mg/mL CALA, 25 mmol/L HP-beta-CD, 0.12 mmol substrate, temperature at
      60  degrees C, agitation speed at 400 rpm, and 48 h for reaction time. Under
      these optimal conditions, the substrate conversion was up to 44.70% and the
      optical purity of the product (R)-2,3-2-PPA was up to 98.20%. This work provides
      an efficient alternative method for lipase-catalyzed enantioselective hydrolysis
      of 2,3-2-PPAME to (R)-2,3-2-PPA by beta-cyclodextrin inclusion in an aqueous
      reaction system of hydrolysis. (c) 2018 American Institute of Chemical Engineers
      Biotechnol. Prog., 2018.

PMID- 30281959
TI  - Sudden Cardiac Death in School Aged Athletes.

PMID- 30281960
TI  - Dosing Exercise for Longevity: How Much is Enough and How Much is Too Much?

PMID- 30281961
TI  - Long Term Strenuous Exercise: Is There a Dose Effect?

PMID- 30281962
TI  - Treatment for Recurrent Odontogenic Keratocysts.
AB  - Controversy remains in understanding both the development and treatment for the
      odontogenic keratocyst (OKC). With recent changes in nomenclature recognizing the
      odontogenic keratocyst as a benign tumor, the debate over the proper course of
      treatment to limit recurrence and morbidity will continue. This study presents
      two cases where conservative treatment failed to prevent recurrence and each
      patient underwent resection of aggressive, multicystic OKCs to provide the best
      chance for definitive care without recurrence and limited morbidity.

PMID- 30281963
TI  - Concurrence of Gemination and Fusion in Maxillary Central Incisors: A Case
      Report.
AB  - This case reports the concurrence of gemination and fusion affecting the
      maxillary central incisors of a twelve-year-old patient and the collaboration of
      the pediatric dentist, endodontist, orthodontist and oral and maxillofacial
      surgeon. Developmental dental anomalies can occur in both primary and permanent
      dentitions as a result of conjoining defects. Double teeth, or cases of
      gemination or fusion, are not exceedingly rare, but the presence of both
      anomalies in a single patient is a rarity. Gemination is the division of a single
      tooth bud, resulting in a large single tooth with a bifid crown and common root
      and root canal. Fusion is the union of two separate tooth buds, resulting in a
      joined tooth with confluence of dentin and separate root canals. Labial
      apexogenesis with MTA, composite resin placement, re-contouring and orthodontic
      care allowed proper alignment with long-term monitoring of growth and development
      for possible incisor replacement.

PMID- 30281964
TI  - Teaching of Fixed Prosthodontics: A Paradigm Shift.
AB  - Restorative dentistry is experiencing a significant shift towards a rising usage
      of tougher all-ceramic materials. This trend must be incorporated into existing
      fixed prosthodontics academic curricula through the integration of lithium
      disilicate and zirconium oxide crown preparation guidelines. In addition, crown
      fabrication techniques have also evolved for these newer materials through
      digitization of preparations and impressions and their computer-assisted
      manufacturing. This article reviews current crown preparation and cementation
      guidelines while describing the teaching program in fixed prosthodontics at the
      University of Tennessee Health Sciences College of Dentistry.

PMID- 30281965
TI  - Introduction to Clinical Practice in Dentistry: Transitioning from Pre-clinical
      to Clinical Student Doctors at The University of Tennessee Health Science Center
      College of Dentistry.
AB  - Matriculation from the pre-clinical setting to the clinical environment is a
      tremendous accomplishment and exemplifies the student's perseverance in learning
      the fundamental concepts necessary for success in the clinical application of
      dentistry. In an effort to maximize its educational philosophy for the teaching
      program, the University of Tennessee's College of Dentistry has implemented
      Introduction to Clinical Practice I and II within the dental curriculum.
      Introduction to Clinical Practice I and II are designed to help the dental
      students effectively and smoothly transition to the clinical setting from the
      classroom and pre-clinical setting. This article describes the university's
      efforts and continuous improvements within the pre-clinical dental curriculum for
      advancing students to the clinics. The purpose of this article is to provide
      helpful information to other dental educational institutions on how to assist
      their pre-clinical dental students in transitioning to clinical student-doctors.

PMID- 30281967
TI  - First Aid Preparedness.
AB  - Having trained personnel ready and willing to render first aid will reassure
      other co-workers and make them feel safer themselves.

PMID- 30281966
TI  - Step-by-Step Resin Bonding of Ceramic Veneers in the Anterior Maxilla: A Case
      Report.
AB  - Applying the biomimetic principles, maximum preservation of the sound tooth
      structure may be achieved by means of adhesive restorations. Due to bonding, it
      is possible to conduct minimally invasive esthetic procedures with laminate
      veneers assuring a high mechanical resistance of the tooth/restoration bond. A
      clinical case of adhesive restorations is presented using the bonding protocol
      respecting the diversity of each product's commercial brands and manufacturer's
      recommendations.

PMID- 30281968
TI  - Corporate Risk and the Growing Case for Sustainable Chemical Management.
AB  - Being responsible for the impact of a chemical disaster-on staff, local
      communities, the environment, and the local economy-is every CEO's nightmare.

PMID- 30281969
TI  - Green Building and Sustainability.
AB  - Increased awareness of not only the value, but the necessity of adopting green
      building initiatives in new builds and retrofits is critical.

PMID- 30281970
TI  - The Economic Implications of Water Shortages.
AB  - Better water management is a key factor in reducing U.S. water consumption that
      can be replicated in other parts of the world.

PMID- 30281971
TI  - Why Are Corporations and Municipalities Moving to Zero Waste?
AB  - Municipalities and states are mandating that large producers of waste food must
      not send it to a landfill. The administration understands that waste food has the
      largest impact on the environment, and large corporations are already striving
      for zero waste (and finding value in the waste they can recycle).

PMID- 30281972
TI  - Role of the Conserved DECH-Box Cysteine in Coupling Hepatitis C Virus Helicase
      Catalyzed ATP Hydrolysis to RNA Unwinding.
AB  - DECH-box proteins are a subset of DExH/D-box superfamily 2 helicases possessing a
      conserved Asp-Glu-Cys-His motif in their ATP binding site. The conserved His
      helps position the Asp and Glu residues, which coordinate the divalent metal
      cation that connects the protein to ATP and activate the water molecule needed
      for ATP hydrolysis, but the role of the Cys is still unclear. This study uses
      site-directed mutants of the model DECH-box helicase encoded by the hepatitis C
      virus (HCV) to examine the role of the Cys in helicase action. Proteins lacking a
      Cys unwound DNA less efficiently than wild-type proteins did. For example, at low
      protein concentrations, a helicase harboring a Gly instead of the DECH-box Cys
      unwound DNA more slowly than the wild-type helicase did, but at higher protein
      concentrations, the two proteins unwound DNA at similar rates. All HCV proteins
      analyzed had similar affinities for ATP and nucleic acids and hydrolyzed ATP in
      the presence of RNA at similar rates. However, in the absence of RNA, all
      proteins lacking a DECH-box cysteine hydrolyzed ATP 10-15 times faster with
      higher Km values, and lower apparent affinities for metal ions, compared to those
      observed with wild-type proteins. These differences were observed with proteins
      isolated from HCV genotypes 2a and 1b, suggesting that this role is conserved.
      These data suggest the helicase needs Cys292 to bind ATP in a state where ATP is
      not hydrolyzed until RNA binds.

PMID- 30281973
TI  - Clearance in Drug Design.
AB  - Due to its implications for both dose level and frequency, clearance rate is one
      of the most important pharmacokinetic parameters to consider in the design of
      drug candidates. Clearance can be classified into three general categories,
      namely metabolic transformation, renal excretion and hepatobiliary excretion.
      Within each category, there are a host of biochemical and physiological
      mechanisms that ultimately determine the clearance rate. Physiochemical
      properties are often indicative of the rate-determining mechanism, with
      lipophilic molecules tending toward metabolism and hydrophilic, polar molecules
      tending toward passive or active excretion. Optimization of clearance requires
      recognition of the major clearance mechanisms and use of the most relevant in
      vitro and in vivo tools to develop structure-clearance relationships. The
      reliability of methods to detect and predict human clearance varies across
      mechanisms. While methods for metabolic and passive renal clearance have proven
      reasonably robust, there is a clear need for better tools to support the
      optimization of transporter-mediated clearance.

PMID- 30281974
TI  - Mechanistic Studies on the Base-Promoted Conversion of Alkoxy-Substituted, Ring
      Fused gem-Dihalocyclopropanes into Furans: Evidence for a Process Involving
      Electrocyclic Ring Closure of a Carbonyl Ylide Intermediate.
AB  - The mechanism associated with the base-promoted conversion of alkoxy-substituted
      and ring-fused gem-dihalocyclopropanes such as 40 into annulated furans has been
      explored. Treatment of compound 40 with potassium tert-butoxide affords a mixture
      of furans 23/27 and 41, an outcome that suggests the intermediacy of the slowly
      interconverting carbonyl ylides 42 and 43 that undergo rapid [1,5]
      electrocyclizations and subsequent dehydrohalogenation to afford the observed
      products. This proposal is supported by ab initio MO and DFT calculations that
      also suggest a vinylcarbene insertion pathway is less likely to be operative.

PMID- 30281975
TI  - Cryo-EM Visualization of an Active High Open Probability CFTR Anion Channel.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) anion channel,
      crucial to epithelial salt and water homeostasis, and defective due to mutations
      in its gene in patients with cystic fibrosis, is a unique member of the large
      family of ATP-binding cassette transport proteins. Regulation of CFTR channel
      activity is stringently controlled by phosphorylation and nucleotide binding.
      Structural changes that underlie transitions between active and inactive
      functional states are not yet fully understood. Indeed the first 3D structures of
      dephosphorylated, ATP-free, and phosphorylated ATP-bound states were only
      recently reported. Here we have determined the structure of inactive and active
      states of a thermally stabilized CFTR, the latter with a very high channel open
      probability, confirmed after reconstitution into proteoliposomes. These
      structures, obtained at nominal resolution of 4.3 and 6.6 A, reveal a unique
      repositioning of the transmembrane helices and regulatory domain density that
      provide insights into the structural transition between active and inactive
      functional states of CFTR. Moreover, we observe an extracellular vestibule that
      may provide anion access to the pore due to the conformation of transmembrane
      helices 7 and 8 that differs from the previous orthologue CFTR structures. In
      conclusion, our work contributes detailed structural information on an active,
      open state of the CFTR anion channel.

PMID- 30281977
TI  - Challenges and Benefits of Repurposing Licensed/Approved/Cleared Products for a
      Radiation Indication.
AB  - Increasingly, the risk of a radiological or nuclear public health emergency is a
      major concern for the U.S. government. To address a potential incident and ensure
      that the U.S. Government is prepared to respond to any civilian or military
      casualties that could result, the U.S. Department of Health and Human Services
      (HHS), together with the Department of Defense, has been charged with the
      development of medical countermeasures (MCMs) to treat individuals experiencing
      acute and delayed injuries that can result from exposure to radiation. With
      limited research and development budgets, and the high costs associated with
      bringing promising approaches from the bench through advanced product development
      activities, and ultimately, to regulatory approval, the U.S. Government places a
      priority on repurposing drugs that have already been commercialized for other
      indications in humans. To address the benefits and challenges of repurposing
      licensed products for a radiation indication, the National Institute of Allergy
      and Infectious Diseases convened a workshop with participants from U.S.
      Government agencies and industry, as well as academic subject matter experts.
      Topics included U.S. Government efforts (e.g., funding, regulatory, stockpiling
      and innovative ways to make drugs available for study), as well as the unique
      regulatory and other challenges faced when repurposing branded or generic drugs.

PMID- 30281976
TI  - A Mechanistic Investigation of Methylene Blue and Heparin Interactions and Their
      Photoacoustic Enhancement.
AB  - We recently reported a real-time method to measure heparin in human whole blood
      based on the photoacoustic change of methylene blue (MB). Intriguingly, the MB
      behaved unlike other "turn on" photoacoustic probes-the absorbance decreased as
      the photoacoustic signal increased. The underlying mechanism was not clear and
      motivated this study. We studied the binding mechanism of MB and heparin in water
      and phosphate buffer saline (PBS) with both experimental and computational
      methods. We found that the photoacoustic enhancement of the MB-heparin mixture
      was a result of MB-heparin aggregation due to charge neutralization and resulting
      sequestration of MB in these aggregates. The sequestration of MB in the MB
      heparin aggregates led to decreased absorbance-there was simply less free dye in
      solution to absorb light. The highest photoacoustic signal and aggregation
      occurred when the number of negatively charged sulfate groups on heparin was
      approximately equal to the number of positively charged MB molecule. The MB
      heparin aggregates dissociated when there were more sulfated groups from heparin
      than MB molecules because of the electrostatic repulsion between negatively
      charged sulfate groups. PBS facilitated MB dimer formation regardless of heparin
      concentration and reprecipitated free MB in aggregates due to ionic strength and
      ionic shielding. Further molecular dynamics experiments found that binding of
      heparin occurred at the sulfates and glucosamines in heparin. Phosphate ions
      could interact with the heparin via sodium ions to impair the MB-heparin binding.
      Finally, our model found 3.7-fold more MB dimerization upon addition of heparin
      in MB solution confirming that heparin facilitates MB aggregation. We conclude
      that the addition of heparin in MB decreases the absorbance of the sample because
      of MB-heparin aggregation leading to fewer MB molecules in solution; however, the
      aggregation also increases the PA intensity because the MB molecules in the MB
      heparin aggregate have reduced degrees of freedom and poor heat transfer to
      solvent.

PMID- 30281978
TI  - Promising vaccines for treating glioblastoma.
AB  - INTRODUCTION: Conventional therapies for glioblastoma  (GBM) typically fail to
      provide lasting antitumor benefits, owing to their inability to specifically
      eliminate all malignant cells. Cancer vaccines are currently being evaluated as a
      means to direct the adaptive immune system to target residual GBM cells that
      remain following standard-of-care treatment. Areas covered: In this review, we
      provide an overview of the more noteworthy cancer vaccines that are under
      investigation for the treatment of GBM, as well as potential future directions
      that may enhance GBM-vaccine effectiveness. Expert opinion: To date, no cancer
      vaccines have been proven effective against GBM; however, only a few have reached
      phase III clinical testing. Clinical immunological monitoring data suggest that
      GBM vaccines are capable of stimulating immune responses reactive to GBM
      antigens, but whether these responses have an appreciable antitumor effect on GBM
      is still uncertain. Nevertheless, there have been several promising outcomes in
      early phase clinical trials, which lend encouragement to this area of study.
      Further studies with GBM vaccines are, therefore, warranted.

PMID- 30281979
TI  - Fatal Encephalitis Associated with Borna Disease Virus 1.

PMID- 30281980
TI  - COMMANDER HF - A Trial and an Answer.

PMID- 30281981
TI  - A Tricky Diagnosis.

PMID- 30281982
TI  - Acne Vulgaris.

PMID- 30281983
TI  - The Name of the Dog.

PMID- 30281985
TI  - Woltman's Sign of Hypothyroidism.

PMID- 30281984
TI  - Fatal Encephalitic Borna Disease Virus 1 in Solid-Organ Transplant Recipients.

PMID- 30281986
TI  - Brittle Nails and Hair Loss in Hypothyroidism.

PMID- 30281987
TI  - Azithromycin and Childhood Mortality in Africa.

PMID- 30281989
TI  - Physician as Double Agent - Conflicting Duties Arising from Employer-Sponsored
      Wellness Programs.

PMID- 30281988
TI  - A Candida auris Outbreak and Its Control in an Intensive Care Setting.
AB  - BACKGROUND: Candida auris is an emerging and multidrug-resistant pathogen. Here
      we report the epidemiology of a hospital outbreak of C. auris colonization and
      infection. METHODS: After identification of a cluster of C. auris infections in
      the neurosciences intensive care unit (ICU) of the Oxford University Hospitals,
      United Kingdom, we instituted an intensive patient and environmental screening
      program and package of interventions. Multivariable logistic regression was used
      to identify predictors of C. auris colonization and infection. Isolates from
      patients and from the environment were analyzed by whole-genome sequencing.
      RESULTS: A total of 70 patients were identified as being colonized or infected
      with C. auris between February 2, 2015, and August 31, 2017; of these patients,
      66 (94%) had been admitted to the neurosciences ICU before diagnosis. Invasive C.
      auris infections developed in 7 patients. When length of stay in the
      neurosciences ICU and patient vital signs and laboratory results were controlled
      for, the predictors of C. auris colonization or infection included the use of
      reusable skin-surface axillary temperature probes (multivariable odds ratio,
      6.80; 95% confidence interval [CI], 2.96 to 15.63; P<0.001) and systemic
      fluconazole exposure (multivariable odds ratio, 10.34; 95% CI, 1.64 to 65.18;
      P=0.01). C. auris was rarely detected in the general environment. However, it was
      detected in isolates from reusable equipment, including multiple axillary skin
      surface temperature probes. Despite a bundle of infection-control interventions,
      the incidence of new cases was reduced only after removal of the temperature
      probes. All outbreak sequences formed a single genetic cluster within the C.
      auris South African clade. The sequenced isolates from reusable equipment were
      genetically related to isolates from the patients. CONCLUSIONS: The transmission
      of C. auris in this hospital outbreak was found to be linked to reusable axillary
      temperature probes, indicating that this emerging pathogen can persist in the
      environment and be transmitted in health care settings. (Funded by the National
      Institute for Health Research Health Protection Research Unit in Healthcare
      Associated Infections and Antimicrobial Resistance at Oxford University and
      others.).

PMID- 30281990
TI  - A Shocking Turn of Events.

PMID- 30281991
TI  - Cabozantinib in Hepatocellular Carcinoma.

PMID- 30281992
TI  - Acceleration of BMI in Early Childhood and Risk of Sustained Obesity.
AB  - BACKGROUND: The dynamics of body-mass index (BMI) in children from birth to
      adolescence are unclear, and whether susceptibility for the development of
      sustained obesity occurs at a specific age in children is important to determine.
      METHODS: To assess the age at onset of obesity, we performed prospective and
      retrospective analyses of the course of BMI over time in a population-based
      sample of 51,505 children for whom sequential anthropometric data were available
      during childhood (0 to 14 years of age) and adolescence (15 to 18 years of age).
      In addition, we assessed the dynamics of annual BMI increments, defined as the
      change in BMI standard-deviation score per year, during childhood in 34,196
      children. RESULTS: In retrospective analyses, we found that most of the
      adolescents with normal weight had always had a normal weight throughout
      childhood. Approximately half (53%) of the obese adolescents had been overweight
      or obese from 5 years of age onward, and the BMI standard-deviation score further
      increased with age. In prospective analyses, we found that almost 90% of the
      children who were obese at 3 years of age were overweight or obese in
      adolescence. Among the adolescents who were obese, the greatest acceleration in
      annual BMI increments had occurred between 2 and 6 years of age, with a further
      rise in BMI percentile thereafter. High acceleration in annual BMI increments
      during the preschool years (but not during the school years) was associated with
      a risk of overweight or obesity in adolescence that was 1.4 times as high as the
      risk among children who had had stable BMI. The rate of overweight or obesity in
      adolescence was higher among children who had been large for gestational age at
      birth (43.7%) than among those who had been at an appropriate weight for
      gestational age (28.4%) or small for gestational age (27.2%), which corresponded
      to a risk of adolescent obesity that was 1.55 times as high among those who had
      been large for gestational age as among the other groups. CONCLUSIONS: Among
      obese adolescents, the most rapid weight gain had occurred between 2 and 6 years
      of age; most children who were obese at that age were obese in adolescence.
      (Funded by the German Research Council for the Clinical Research Center "Obesity
      Mechanisms" and others; ClinicalTrials.gov number, NCT03072537 .).

PMID- 30281993
TI  - Enzalutamide in Castration-Resistant Prostate Cancer.

PMID- 30281994
TI  - Dialysis-Facility Joint-Venture Ownership - Hidden Conflicts of Interest.

PMID- 30281995
TI  - Primary Prevention of Cardiovascular Disease with a Mediterranean Diet
      Supplemented with Extra-Virgin Olive Oil or Nuts.

PMID- 30281996
TI  - Next-Generation Sequencing to Diagnose Suspected Genetic Disorders.

PMID- 30281997
TI  - Determinants of Risk for Childhood Obesity.

PMID- 30281998
TI  - Breast Cancer in Men.

PMID- 30281999
TI  - Optimization of maintenance therapy of Risperidone with CYP2D6 genetic
      polymorphisms through an extended translational framework-based prediction of
      target occupancies/clinical outcomes.
AB  - Risperidone, one of the second-generation antipsychotics, can efficiently target
      dopamine D2 and serotonin 5-HT2A receptors. There actually exists significant
      implication of CYP2D6 genetic polymorphisms on the metabolic kinetics of
      risperidone, little is known about the extent of CYP2D6 impacting human D2 and 5
      HT2A receptor occupancies as well as the clinical efficacy and efficacy in
      schizophrenia treatment. Here we assessed the influences of CYP2D6 gene
      polymorphisms on human target occupancies/clinical outcomes and optimized the
      maintenance therapy of risperidone. A translational framework, previously
      developed using in vitro and in vivo information in rats, was used as the basis
      for integrating the effects of CYP2D6 genetic polymorphisms on target occupancies
      and clinical outcomes. D2 occupancy as a biomarker was related to Positive and
      Negative Syndrome Scale (PANSS) response and Simpson-Angus Scale (SAS). The
      population approach was applied to characterize pharmacokinetic and
      pharmacodynamic (PK/PD) profiles of risperidone. Non-compartment analysis method
      was performed to calculate the steady state PK/PD parameters of both risperidone
      and 9-hydroxyrisperidone. The predictive power of this extended translational
      framework was determined by comparing the predictions of target occupancies and
      clinical outcomes with the reported human values of risperidone at clinically
      suggested dosage of 4.0 mg/day. This extended translational framework was
      adequately used to predict human target occupancies and clinical outcomes. At the
      steady state, D2 ROs were 75.8%, 79.3% and 86.0% for CYP2D6 poor metabolizer
      (PM), intermediate metabolizer (IM) and extensive metabolizer (EM), respectively;
      5-HT2A ROs were 96.4%, 97.2% and 98.4% for CYP2D6 PM, IM and EM, respectively;
      PANSS changes from placebo were -5.3, -7.7 and -11.3 for CYP2D6 PM, IM and EM,
      respectively; SAS changes from placebo were 0.13, 0.15 and 0.18 for CYP2D6 PM, IM
      and EM, respectively. The predictions of human D2, 5-HT2A RO, PANSS and SAS
      changes for risperidone with CYP2D6 genetic polymorphisms were well in line with
      the reported values in clinic. 5.0, 4.0 and 2.5 mg/day were the equivalent
      dosages of risperidone for CYP2D6 PM, IM and EM, respectively. The optimized
      maintenance therapy of risperidone was provided through the Three-Step method and
      the dosage range was 2.5-5.0 mg/day for three CYP2D6 gene groups in the present
      study. Taken together, our findings demonstrate that this extended translational
      framework not only differentiates the effects of CYP2D6 genetic polymorphisms on
      target occupancies and clinical outcomes, but also constitutes a scientific basis
      to optimize the maintenance therapy of neuropsychiatric patients in clinic.

PMID- 30282000
TI  - Presence of human herpes virus 1-thymidine kinase in testis of azoospermic
      infertile herpes-infected patients.
AB  - Infection with human herpes virus 1 (HHV1) is a suspected cause of human male
      infertility. However, the correlation between HHV1 infection and infertility is
      still unclear. We have previously generated transgenic rats that ectopically
      express the HHV1 thymidine kinase gene (HHV1-TK) in post-meiotic spermatids and
      found they had aberrant spermatogenesis and infertility. Therefore, we
      hypothesized that human infertility might be caused by HHV1 infection. Here, we
      examined whether HHV1-TK is expressed in human testis by analyzing the presence
      of its transcript and protein. Specimens were collected by biopsy from 30
      azoospermic infertile male patients. RT-PCR and immunohistochemistry showed that
      23 patients were positive for HHV1-TK expression, while seven patients were
      negative. Thus, we demonstrated HHV1-TK expression, indicating HHV1 infection, in
      the testis of human azoospermic infertile males for the first time; our findings
      represent a great advancement toward the verification of our hypothesis that HHV1
      TK expression might cause human infertility.

PMID- 30282001
TI  - Different aspects of platelet evaluation in dengue: Measurement of circulating
      mediators, ability to interact with the virus, the degree of activation and
      quantification of intraplatelet protein content.
AB  - Platelets play a role in hemostasis, coagulation, angiogenesis, inflammation and
      immune response is one of the most affected cells in dengue. Here we describe
      some aspects of platelets by observing their specific circulating mediators, the
      ability to interact with the virus and morphological consequences of this
      interaction, activation markers and intraplatelet protein contents in dengue. We
      conducted this study using dengue-patients as well as healthy donors.
      Immunoenzymatic assay, flow cytometry, transmission electron microscopy and
      intraplatelet proteins expression assays were carried out. Briefly, we found an
      increase in sCD62L, NO or TBX2 ratio in platelet count, mostly in patients with
      the worse clinical outcome. After in vitro DENV infection or during natural
      infection, platelets underwent morphological alteration with increased expression
      of platelet activation markers, particularly in natural infections. Analysis of
      intraplatelet protein contents revealed different angiogenic and inflammatory
      profiles, maintaining or not extracellular matrix integrity between DF and DFWS
      patients. Thus, platelets are frequently affected by dengue, either by altering
      their own functionality, as "carrier" of the virus, or as an antiviral and
      mediator-secreting effector cell. Thus, strategies aimed at recovering platelet
      amounts in dengue seem to be essential for a better clinical outcome of the
      patients.

PMID- 30282002
TI  - Effects of Chronic Spinal Cord Injury on Relationships among Ion Channel and
      Receptor mRNAs in Mouse Lumbar Spinal Cord.
AB  - Spinal cord injury (SCI) causes widespread changes in gene expression of the
      spinal cord, even in the undamaged spinal cord below the level of the lesion.
      Less is known about changes in the correlated expression of genes after SCI. We
      investigated gene co-expression networks among voltage-gated ion channel and
      neurotransmitter receptor mRNA levels using quantitative RT-PCR in longitudinal
      slices of the mouse lumbar spinal cord in control and chronic SCI animals. These
      longitudinal slices were made from the ventral surface of the cord, thus forming
      slices relatively enriched in motor neurons or interneurons. We performed
      absolute quantitation of mRNA copy number for 50 ion channel or receptor
      transcripts from each sample, and used multiple correlation analyses to detect
      patterns in correlated mRNA levels across all pairs of genes. The majority of
      channels and receptors changed in expression as a result of chronic SCI, but did
      so differently across slice levels. Furthermore, motor neuron-enriched slices
      experienced an overall loss of correlated channel and receptor expression, while
      interneuron slices showed a dramatic increase in the number of positively
      correlated transcripts. These correlation profiles suggest that spinal cord
      injury induces distinct changes across cell types in the organization of gene co
      expression networks for ion channels and transmitter receptors.

PMID- 30282003
TI  - Seasonal and spatial distribution of Aedes aegypti and Aedes albopictus in a
      municipal urban park in Sao Paulo, SP, Brazil.
AB  - Dengue, yellow fever, chikungunya and Zika are important arboviruses present in
      various countries of the world, the etiological agents of which are transmitted
      to human-beings by the bite of infected females of Aedes aegypti and Aedes
      albopictus. Biological aspects of these vectors, such as their distribution and
      abundance, are influenced by climatic variables such as rainfall and temperature.
      We assess the spatial and seasonal distribution of Ae. aegypti and Ae.
      albopictus, during spring 2014 and spring 2015 and autumn 2015 and autumn 2016,
      in an urban Municipal Park, Sao Paulo (SP, Brazil), using 36 ovitraps. The Park
      was divided into three areas: internal, intermediate and peripheral, and 12 geo
      referenced ovitraps were randomly installed in each area. We evaluated the
      association between the environmental variables maximum and minimum temperatures
      and rainfall with oviposition rates in the park using negative binomial
      regression models. Further, to estimate the distribution of the species in the
      three areas during the seasons, we employed the geostatic interpolation method
      with the use of kriging. Our results show the presence of the two species in the
      area in both the seasons but with a greater predominance of Ae. albopictus. Both
      species were significantly more abundant in spring than autumn. However, our
      results suggested that this seasonal variation was mediated by the maximum and
      minimum temperatures, which were significantly associated with the oviposition
      rate of both species, in all regression models. Cumulative rainfall of the week
      of collection was not associated with the abundance of the vectors in the
      multiple models. Moreover, regardless of climatic variables, the oviposition of
      Ae. aegypti was positively associated with the peripheral area of the park
      compared with the internal area (oviposition rate ratio [ORR]: 4.92; 95% CI: 2.46
      9.83). On the other hand, the oviposition of Ae. albopictus was negatively
      associated with the peripheral area as compared with the internal one (ORR: 0.59;
      95% CI: 0.38-0.91). The spatial distribution revealed a pattern of spatial
      segregation, confirming the ecological preferences of each species. Green areas
      in urban centers can serve as important habitats for various mosquito species,
      including especially Ae. albopictus. Thus it is that our study highlights the
      importance of maintaining surveillance for the targeting of control strategies in
      green areas as well, since most control strategies are focused on Ae. aegypti and
      urban residential centers.

PMID- 30282004
TI  - Clustering-based multi-view network fusion for estimating brain network atlases
      of healthy and disordered populations.
AB  - BACKGROUND: While several research methods were developed to estimate individual
      based representations of brain connectional wiring (i.e., a connectome),
      traditionally captured using multimodal MRI data (e.g., functional and diffusion
      MRI), very limited works aimed to estimate brain network atlas for a population
      of connectomes. Estimating well-representative brain templates is a key step for
      group comparison studies. However, estimating a network atlas for a population of
      multi-source brain connectomes lying on different manifolds is absent. NEW
      METHOD: To fill this gap, we propose a cluster-based multi-view brain
      connectivity fusion framework to estimate a brain network atlas for a population
      of multi-view brain networks, where each view captures a specific facet of the
      brain construct. Specifically, given a population of subjects, each with multi
      view networks, we first non-linearly fuse multi-view networks into a single fused
      network for each subject. Then, we cluster the fused networks to identify
      individuals sharing similar connectional traits in an unsupervised way, which are
      next averaged within each cluster to generate a representative network atlas.
      Finally, we construct the final multi-view network atlas by averaging the
      obtained templates of all clusters. RESULTS: We evaluated our method on both
      healthy and disordered populations (with autism and dementia) and spotted
      differences between network atlases for healthy and autistic groups. COMPARISON
      WITH EXISTING METHODS AND CONCLUSIONS: Compared to other baseline methods, our
      fusion strategy achieved the best results in terms of template centeredness and
      population representativeness.

PMID- 30282005
TI  - Paracetamol-induced liver injury modelled in Xenopus laevis embryos.
AB  - INTRODUCTION: Failure to predict drug-induced liver injury (DILI) remains a major
      contributing factor to lead compound drop-out during drug development. Xenopus
      embryos are amenable for early stage medium throughput small molecule screens and
      so have the potential to be used in pre-clinical screens. To begin to assess the
      usefulness and limitations of Xenopus embryos for safety assessment in the early
      phases of drug development, paracetamol was used as a model hepatotoxin.
      Paracetamol overdose is associated with acute liver injury. In mammals, the main
      mechanism of paracetamol-induced acute liver injury is an increased amount of the
      reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI) combined with a
      reduction of free glutathione (GSH). Humans that have taken an overdose of
      paracetamol are often treated with N-acetyl cysteine (NAC). METHOD: Xenopus
      laevis embryos were treated with up to 5 mM paracetamol from stage 38 to stage 45
      during development, when the liver is functional. The presence of paracetamol
      induced liver injury was assessed by: (Dart et al., 2006) microRNA-122 (miR-122)
      expression (a hepatic marker), (Jaeschke, 2015) free GSH concentration (a marker
      of oxidative stress) and (Larson et al., 2005) NAC antioxidant intervention.
      RESULTS: The amount of free GSH decreased significantly in embryos exposed to
      increasing paracetamol concentration. In embryos exposed to 5 mM paracetamol,
      22.57 +/- 4.25 nmol/mg GSH was detected compared to 47.11 +/- 7.31 nmol/mg
      untreated embryos (mean +/- SEM). In tail tissue, miRNA-122 expression increased
      6.3-fold with 3 mM paracetamol concentration treatment compared to untreated
      embryos. NAC treatment altered the free GSH decline for embryos treated with up
      to 5 mM. Embryos exposed to 1 mM paracetamol and then exposed to 0.5 mM NAC 24 h
      prior to harvest, had an significantly higher amount GSH compared to embryos that
      were only exposed to 1 mM paracetamol (mean +/- SEM; 97.1 +/- 9.6 nmol/mg and
      54.5 +/- 6.6 nmol/mg respectively). CONCLUSION: Xenopus laevis embryos exhibit
      similar characteristics of paracetamol-induced liver injury observed in mammalian
      models. These data indicate that the Xenopus embryo could be a useful in vivo
      model to assess DILI and aid lead compound prioritisation during the early phase
      of drug development, in combination with pre-clinical in vitro studies.
      Consequently, the Xenopus embryo could contribute to the reduction principle as
      defined by the National Centre for the Replacement, Refinement and Reduction of
      Animals in Research.

PMID- 30282006
TI  - In vitro human skin permeation and decontamination of diisopropyl
      methylphosphonate (DIMP) using Dermal Decontamination Gel (DDGel) and Reactive
      Skin Decontamination Lotion (RSDL) at different timepoints.
AB  - This study compared the efficiency for in vitro human skin decontamination using
      DDGel and RSDL when applied at different timepoints (5 min and 90 min).
      Experiments were performed using in vitro human skin models, in which skin was
      mounted onto Flow-Through diffusion cells. The mass of 14-C DIMP removed from
      skin surface after decontamination was quantitated by measuring radioactivity
      with a liquid scintillation spectrometer. Both decontaminants removed more than
      90% recovery dose of DIMP from skin compared to control group (p < 0.05). DDGel
      skin decontamination reduced more toxicant amount when compared to RSDL. DDGel
      showed slight higher decontamination ability of DIMP than RSDL and efficiently
      removed chemicals from the skin surface, also reduced the amount of DIMP in
      receptor fluid. A similar decontamination regimen with RSDL and DDGel at 90 min
      showed that both were still might effectively increase the time window of
      opportunity for treatment. Thus, DDGel can offer a potential as a next generation
      skin decontamination platform technology for military and civilian applications.

PMID- 30282008
TI  - Protective effects of quercetin against brain injury in a rat model of
      lipopolysaccharide-induced fetal brain injury.
AB  - Maternal exposure to lipopolysaccharide (LPS), a bacterial endotoxin produced
      during infection, leads to disruption in fetal brain development and causes
      newborn brain injury. Quercetin (QR) is a multipotent flavonoid that functions as
      an antioxidant and protects against inflammation and neurodegeneration. In this
      study, we explored the potential functions of QR in alleviating maternal LPS
      exposure induced fetal brain damage. Pregnant rats at late gestational stages
      were treated with saline, LPS, QR, LPS and QR. Brain injury biomarker TGF-1beta
      was assessed in cerebrospinal fluid (CSF) and brain tissue of newborn rats. Pro
      inflammatory cytokines, apoptosis markers and oxidative stress indicators were
      evaluated. We found that LPS treatment induced an increased production of TGF
      1beta which was suppressed by QR administration. LPS enhanced pro-apoptotic Bax
      and inhibited anti-apoptotic Bcl-2 expression. QR reduced that ratio of Bax and
      Bcl-2 that was high in LPS treated brain tissue. Additionally, QR suppressed
      oxidative stress induced by LPS. Finally, QR reduced the levels of pro
      inflammatory cytokines that were produced as a result of LPS exposure. In
      summary, our study indicates that QR potently alleviates maternal LPS exposure
      induced fetal brain injury in rats, making it a potential therapeutic for
      suppressing infant brain damage as a result of maternal infection.

PMID- 30282007
TI  - Towards microstructure fingerprinting: Estimation of tissue properties from a
      dictionary of Monte Carlo diffusion MRI simulations.
AB  - Many closed-form analytical models have been proposed to relate the diffusion
      weighted magnetic resonance imaging (DW-MRI) signal to microstructural features
      of white matter tissues. These models generally make assumptions about the tissue
      and the diffusion processes which often depart from the biophysical reality,
      limiting their reliability and interpretability in practice. Monte Carlo
      simulations of the random walk of water molecules are widely recognized to
      provide near groundtruth for DW-MRI signals. However, they have mostly been
      limited to the validation of simpler models rather than used for the estimation
      of microstructural properties. This work proposes a general framework which
      leverages Monte Carlo simulations for the estimation of physically interpretable
      microstructural parameters, both in single and in crossing fascicles of axons.
      Monte Carlo simulations of DW-MRI signals, or fingerprints, are pre-computed for
      a large collection of microstructural configurations. At every voxel, the
      microstructural parameters are estimated by optimizing a sparse combination of
      these fingerprints. Extensive synthetic experiments showed that our approach
      achieves accurate and robust estimates in the presence of noise and uncertainties
      over fixed or input parameters. In an in vivo rat model of spinal cord injury,
      our approach provided microstructural parameters that showed better
      correspondence with histology than five closed-form models of the diffusion
      signal: MMWMD, NODDI, DIAMOND, WMTI and MAPL. On whole-brain in vivo data from
      the human connectome project (HCP), our method exhibited spatial distributions of
      apparent axonal radius and axonal density indices in keeping with ex vivo
      studies. This work paves the way for microstructure fingerprinting with Monte
      Carlo simulations used directly at the modeling stage and not only as a
      validation tool.

PMID- 30282010
TI  - Evaluation of the mucoadhesive properties of chitosan nanoparticles prepared
      using different chitosan to tripolyphosphate (CS:TPP) ratios.
AB  - Mucoadhesive molecules such as chitosan, can allow targeting of a particular
      tissue to prolong residence time and subsequently improve bioavailability. The
      purpose of this study was to investigate chitosan-tripolyphosphate (CS:TPP)
      nanoparticles and to evaluate the interaction between nanoparticles of different
      CS:TPP ratios with mucin using viscosity, particle size analysis and zeta
      potential. For all CS:TPP ratios examined, a minimum value of viscosity was
      reached for a 3:1 CS:TPP ratio, however chitosan nanoparticles at this ratio were
      not stable (<+30 mV), whereas a CS:TPP ratio of 4:1 displayed the strongest
      interaction. This suggests a minimum CS:TPP ratio of 4:1 is required to produce
      stable nanoparticles able to form strong interactions, which is consistent with a
      greater mucin binding efficiencies at CS:TPP ratios of 4:1 and higher, which were
      quantified using a colorimetric assay. Further analysis of similar systems could
      lead potentially to tuneable chitosan nanoparticles for specific applications.

PMID- 30282011
TI  - Rehmannia glutinosa polysaccharide functions as a mucosal adjuvant to induce
      dendritic cell activation in mediastinal lymph node.
AB  - In our previous study, we showed that Rehmannia glutinosa polysaccharide (RGP)
      treatment induced activation of dendritic cells (DCs) in human and mouse
      subjects. In this study, we evaluated the effect of RGP as a mucosal adjuvant for
      inducting activation of DCs in the mediastinal lymph node (mLN) in the mouse. The
      C57BL/6 mice were intranasally (i.n.) treated with RGP and activation of DC in
      the mLN was analyzed. The treatment with RGP induced a substantial increase in
      the number of DCs in the mLN due to the up-regulation of C-C motif chemokine
      receptor 7 (CCR7) in the DCs. Moreover, the expression of co-stimulatory
      molecules in the mLN DCs and the concentration of pro-inflammatory cytokines in
      the lung were up-regulated by RGP treatment. Also, RGP treatment induced
      interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha)
      production in the mLN T cells. The combination treatment of RGP and ovalbumin
      (OVA) induced OVA-specific TCR transgenic I (OT-I) and OT-II cell proliferation
      in the mLN. Finally, the combination treatment of RGP and tyrosinase-related
      protein 2 (TRP2) peptide, a melanoma self-antigen, protected mice from melanoma
      challenge. Thus, these data demonstrated that RGP can be used as a mucosal
      adjuvant for inducing activation of immune responses in the lung.

PMID- 30282012
TI  - Extraction and antioxidant activities of cushaw polysaccharide.
AB  - Extraction and antioxidant activities of polysaccharide from cushaw were studied.
      The crude polysaccharide was extracted with the hot-water. It proved that the
      CaCl2 method was very suitable for deproteinization to cushaw polysaccharide. The
      cushaw polysaccharide contained alpha/beta glycosidic bonds. Moreover, it proved
      that the cushaw polysaccharide exhibited better antioxidant activities.

PMID- 30282009
TI  - Impact of obesity on the toxicity of a multi-ingredient dietary supplement,
      OxyELITE ProTM (New Formula), using the novel NZO/HILtJ obese mouse model:
      Physiological and mechanistic assessments.
AB  - Herbal dietary supplement (HDS)-induced hepato- and cardiotoxicity is an emerging
      clinical problem. In this study, we investigated the liver and heart toxicity of
      HDS OxyELITE-PROTM New Formula (OEP-NF), a dietary supplement marketed for weight
      loss and performance enhancement that was recently withdrawn from the market.
      Using a novel NZO/HlLtJ obese mouse model, we demonstrated that administration of
      clinically relevant mouse equivalent doses (MED) of OEP-NF produced cardio- and
      hepatotoxic risks following both short- and long-term administration schedules.
      Specifically, gavaging female NZO/HlLtJ with up to 2X MED of OEP-NF resulted in
      40% mortality within two weeks. Feeding mice with either 1X or 3X MED of OEP-NF
      for eight weeks, while not exhibiting significant effects on body weights,
      significantly altered hepatic gene expression, increased the number of apoptotic
      and mast cells in the heart and affected cardiac function. The degree of toxicity
      in NZO/HlLtJ mice was higher than that observed previously in non-obese CD-1 and
      B6C3F1 strains, suggesting that an overweight/obese condition can sensitize mice
      to OEP-NF. Adverse health effects linked to OEP-NF, together with a number of
      other hepato- and cardiotoxicity cases associated with HDS ingestion, argue
      strongly for introduction of quality standards and pre-marketing safety
      assessments for multi-ingredient HDS.

PMID- 30282013
TI  - Chitosan/Ag-hydroxyapatite nanocomposite beads as a potential adsorbent for the
      efficient removal of toxic aquatic pollutants.
AB  - In the present study, the potential of synthesized chitosan/Ag-substituted
      hydroxyapatite nanocomposite beads to remove basic dye, heavy metal and microbes
      from aqueous solutions was investigated. Beads were prepared in different ratios
      via embedding of Ag-hydroxyapatite (Ag-HA) into chitosan (CS) solution. The beads
      were characterized by Fourier transform infrared spectroscopy (FT-IR) and
      scanning electron microscope (SEM) in order to get an insight of the functional
      groups and morphology. Batch adsorption studies were conducted with copper ions
      (Cu (II)) and rhodamine B (RhB) dye by changing several parameters such as Ag-HA
      to Cs ratio, contact time, solution pH and initial concentration of pollutants.
      The antibacterial efficiency of beads was tested under dynamic contact conditions
      against commonly found bacteria in water, Escherichia coli. The adsorption
      isotherm data were best fitted with Langmuir model. The maximum Langmuir
      adsorption capabilities for Cu (II) ions and rhodamine B were found to be 40.11
      mg/g and 127.61 mg/g, respectively. The adsorption process could be best
      described by pseudo-second-order kinetic model for both rhodamine B and Cu(II).
      The percentage removal efficiency of Cu (II) and rhodamine B from tap water and
      untreated river water ranged from 86.7 to 94.4% along with 99.99% of
      decontamination of microbial load.

PMID- 30282014
TI  - Comparison of the effects of calcified green macroalga (Halimeda macroloba
      Decaisne) and commercial CaCO3 on the properties of composite starch foam trays.
AB  - The calcified green macroalga, Halimeda macroloba, is a source of bio-based
      calcium carbonate which can be used as a filler in starch foam tray. In the first
      part of this study, the composition and structure of calcium carbonate of this
      species were investigated using Fourier transform infrared spectrometry (FTIR), X
      ray diffraction (XRD), Energy dispersive X-ray spectroscopy (EDX) and Scanning
      election microscopy (SEM). The morphology of the macroalgal powder particles was
      rod-like and organic materials (e.g. polysaccharide) and calcium carbonate
      (aragonite form) were present. The second part of the study investigated the
      effects of calcium carbonate from H. macroloba on the properties of starch foam
      tray and compared them with the properties of starch foam tray filled with
      commercial CaCO3. Interestingly, the composites starch foam trays with macroalgal
      powder had better impact strength than starch/commercial CaCO3 composite foam
      trays. Moreover, the macroalgal powder affected the thermal properties of the
      starch foam tray equally as well as commercial CaCO3. However, the macroalgal
      powder caused more significant changes in the color parameters and the whiteness
      values of starch foam tray than commercial CaCO3.

PMID- 30282015
TI  - Development of a mass spectrometry method for the characterization of a series of
      chitosan.
AB  - Chitosan has multiple biological activities, but a sensitive and rapid
      characterization method is yet to be developed for its further application. This
      study presented an optional mass spectrometry method for the characterization of
      chitosan. Nine kinds of chitosan (degree of deacetylation (DD), 63.08%-89.06% &
      MW, 106.1-485.0 kDa) were adopted for the method development. Most species of
      chitosan, detected by an ESI-MS technique, were observed below 1000 m/z, which
      seemed that only chito-oligosaccharide (COS) impurities were detected. Then, a
      sensitive UPLC-ESI-MS/MS method was established to assess the COS impurities in
      chitosan, and no COS impurities were detected. However, dissociation of chitosan
      and COSs in the ESI source were observed, and then the mass spectra patterns were
      deeply evaluated via an accurate Q-TOF mass spectrometer. Our research
      demonstrated that the mass spectra of COSs and chitosan resulted from the
      dissociation of glycosidic linkage and dehydration. Although the distribution of
      GlcN and GlcNAc units in these chitosan samples might be different, similar
      dissociation efficiencies were observed. Furthermore, good linearities were
      obtained between the intensities of product ions, detected by an UPLC-pseuedo-MS2
      method, and DDs determined by conventional method. This method could be suitable
      for the DD determination and quantitative analysis of chitosan.

PMID- 30282016
TI  - Virus Assembly Antagonists from Redesigned Antibodies.
AB  - There is no reliable cure for chronic Hepatitis B Virus (HBV). In this issue of
      Structure, Eren et al. (2018) show how antibody-derived proteins bind different
      forms of the HBV capsid protein, blocking assembly. This interaction may also
      affect downstream signaling. These antibody-derived molecules mark a new strategy
      that may ultimately contribute to a cure.

PMID- 30282017
TI  - Unraveling the Mechanism of Procollagen C-Proteinase Enhancer.
AB  - In this issue of Structure, Pulido et al. (2018) determine the crystal structure
      of procollagen C-proteinase enhancer-1 (PCPE-1)/procollagen III complex and
      identify that PCPE-1 unwinds the stalk of the procollagen III trimer, liberating
      a single chain to facilitate binding and cleavage by BMP-1 proteinases for
      subsequent fibrillar collagen assembly.

PMID- 30282018
TI  - The time course of blood brain barrier leakage and its implications on the
      progression of methamphetamine-induced seizures.
AB  - The initial goals of these experiments were to determine: 1) if blood-brain
      barrier (BBB) breakdown was a cause or an effect of METH-induced seizures; 2) all
      the brain regions where BBB is disrupted as seizures progress; and 3) the
      correlations between body temperature and vascular leakage and neurodegeneration.
      A fourth objective was added after initial experimentation to determine if sub
      strain differences existed in adult male C57 B6 J (Jackson laboratories, JAX)
      versus C57 B6N (Charles River, CR) mice involving their susceptibility to BBB
      breakdown and seizure severity. With the 1st "maximal" intensity myoclonic-tonic
      seizure (MCT) varying degrees of IgG infiltration across the BBB (<=1 mm2) were
      prominent in olfactory system (OS) associated regions and in thalamus,
      hypothalamus and neocortex. IgG infiltration areas in the OS-associated regions
      of the bed nucleus of the stria terminalis, septum and more medial amygdala
      nuclei, and the hypothalamus were increased significantly by the time continuous
      behavioral seizures (CBS) developed. Mice receiving METH that had body
      temperatures of >=40  degrees C had IgG infiltration along with MCT or CBS but
      peak body temperatures above 40  degrees C did not significantly increase IgG
      infiltration. Neurodegeneration seen at >=6 h was restricted to the OS in both
      JAX and CR mice and was most prominent in the posteromedial cortical amygdaloid
      nucleus. Neurodegeneration in the anterior septum (tenia tecta) was seen only in
      the JAX mice. We hypothesize that METH-induced hypertension and hyperthermia lead
      to BBB breakdown and other vascular dysfunctions in the OS brain regions
      resulting in OS hyperexcitation. Excitation of the OS neural network then leads
      to the development of seizures. These seizures in turn exacerbate the energy
      depletions and the reactive oxygen stress produced by hyperthermia further
      damaging the BBB and vascular function. These events form a recurrent cycle that
      results in ever increasing seizure activity and neurotoxicity.

PMID- 30282019
TI  - Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein
      BMAL1.
AB  - Circadian clock dysfunction is a common symptom of aging and neurodegenerative
      diseases, though its impact on brain health is poorly understood. Astrocyte
      activation occurs in response to diverse insults and plays a critical role in
      brain health and disease. We report that the core circadian clock protein BMAL1
      regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism
      and a lesser non-cell-autonomous signal from neurons. Astrocyte-specific Bmal1
      deletion induces astrocyte activation and inflammatory gene expression in vitro
      and in vivo, mediated in part by suppression of glutathione-S-transferase
      signaling. Functionally, loss of Bmal1 in astrocytes promotes neuronal death in
      vitro. Our results demonstrate that the core clock protein BMAL1 regulates
      astrocyte activation and function in vivo, elucidating a mechanism by which the
      circadian clock could influence many aspects of brain function and neurological
      disease.

PMID- 30282020
TI  - Mutations in Craniosynostosis Patients Cause Defective Interleukin-11 Receptor
      Maturation and Drive Craniosynostosis-like Disease in Mice.
AB  - Premature closure of the sutures that connect the cranial bones during
      development of the mammalian skull results in a phenotype called
      craniosynostosis. Recently, several craniosynostosis patients with missense
      mutations within the gene encoding the interleukin-11 receptor (IL-11R) have been
      described, but the underlying molecular mechanisms have remained elusive. IL-11
      is a cytokine that has a crucial role in bone remodeling and activates cells via
      binding to the IL-11R. Here, we show that patient mutations prevented maturation
      of the IL-11R, resulting in endoplasmic reticulum retention and diminished cell
      surface appearance. Disruption of a conserved tryptophan-arginine zipper within
      the third domain of the IL-11R was the underlying cause of the defective
      maturation. IL-11 classic signaling via the membrane-bound receptor, but not IL
      11 trans-signaling via the soluble receptor, was the crucial pathway for normal
      skull development in mice in vivo. Thus, the specific therapeutic inhibition of
      IL-11 trans-signaling does not interfere with skull development.

PMID- 30282021
TI  - Single-Cell Analysis of Quiescent HIV Infection Reveals Host Transcriptional
      Profiles that Regulate Proviral Latency.
AB  - A detailed understanding of the mechanisms that establish or maintain the latent
      reservoir of HIV will guide approaches to eliminate persistent infection. We used
      a cell line and primary cell models of HIV latency to investigate viral RNA
      (vRNA) expression and the role of the host transcriptome using single-cell
      approaches. Single-cell vRNA quantitation identified distinct populations of
      cells expressing various levels of vRNA, including completely silent populations.
      Strikingly, single-cell RNA-seq of latently infected primary cells demonstrated
      that HIV downregulation occurred in diverse transcriptomic environments but was
      significantly associated with expression of a specific set of cellular genes. In
      particular, latency was more frequent in cells expressing a transcriptional
      signature that included markers of naive and central memory T cells. These data
      reveal that expression of HIV proviruses within the latent reservoir are
      influenced by the host cell transcriptional program. Therapeutic modulation of
      these programs may reverse or enforce HIV latency.

PMID- 30282022
TI  - Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates
      Microglia Activation during Viral Encephalitis.
AB  - In sterile neuroinflammation, a pathological role is proposed for microglia,
      whereas in viral encephalitis, their function is not entirely clear. Many viruses
      exploit the odorant system and enter the CNS via the olfactory bulb (OB). Upon
      intranasal vesicular stomatitis virus instillation, we show an accumulation of
      activated microglia and monocytes in the OB. Depletion of microglia during
      encephalitis results in enhanced virus spread and increased lethality.
      Activation, proliferation, and accumulation of microglia are regulated by type I
      IFN receptor signaling of neurons and astrocytes, but not of microglia.
      Morphological analysis of myeloid cells shows that type I IFN receptor signaling
      of neurons has a stronger impact on the activation of myeloid cells than of
      astrocytes. Thus, in the infected CNS, the cross talk among neurons, astrocytes,
      and microglia is critical for full microglia activation and protection from
      lethal encephalitis.

PMID- 30282025
TI  - Visual Motion Processing in Macaque V2.
AB  - In the primate visual system, direction-selective (DS) neurons are critical for
      visual motion perception. While DS neurons in the dorsal visual pathway have been
      well characterized, the response properties of DS neurons in other major visual
      areas are largely unexplored. Recent optical imaging studies in monkey visual
      cortex area 2 (V2) revealed clusters of DS neurons. This imaging method
      facilitates targeted recordings from these neurons. Using optical imaging and
      single-cell recording, we characterized detailed response properties of DS
      neurons in macaque V2. Compared with DS neurons in the dorsal areas (e.g., middle
      temporal area [MT]), V2 DS neurons have a smaller receptive field and a stronger
      antagonistic surround. They do not code speed or plaid motion but are sensitive
      to motion contrast. Our results suggest that V2 DS neurons play an important role
      in figure-ground segregation. The clusters of V2 DS neurons are likely
      specialized functional systems for detecting motion contrast.

PMID- 30282023
TI  - Transsynaptic Binding of Orphan Receptor GPR179 to Dystroglycan-Pikachurin
      Complex Is Essential for the Synaptic Organization of Photoreceptors.
AB  - Establishing synaptic contacts between neurons is paramount for nervous system
      function. This process involves transsynaptic interactions between a host of cell
      adhesion molecules that act in cooperation with the proteins of the extracellular
      matrix to specify unique physiological properties of individual synaptic
      connections. However, understanding of the molecular mechanisms that generate
      functional diversity in an input-specific fashion is limited. In this study, we
      identify that major components of the extracellular matrix proteins present in
      the synaptic cleft-members of the heparan sulfate proteoglycan (HSPG) family
      associate with the GPR158/179 group of orphan receptors. Using the mammalian
      retina as a model system, we demonstrate that the HSPG member Pikachurin,
      released by photoreceptors, recruits a key post-synaptic signaling complex of
      downstream ON-bipolar neurons in coordination with the pre-synaptic dystroglycan
      glycoprotein complex. We further demonstrate that this transsynaptic assembly
      plays an essential role in synaptic transmission of photoreceptor signals.

PMID- 30282024
TI  - Sub-populations of Spinal V3 Interneurons Form Focal Modules of Layered Pre-motor
      Microcircuits.
AB  - Layering of neural circuits facilitates the separation of neurons with high
      spatial sensitivity from those that play integrative temporal roles. Although
      anatomical layers are readily identifiable in the brain, layering is not
      structurally obvious in the spinal cord. But computational studies of motor
      behaviors have led to the concept of layered processing in the spinal cord. It
      has been postulated that spinal V3 interneurons (INs) play multiple roles in
      locomotion, leading us to investigate whether they form layered microcircuits.
      Using patch-clamp recordings in combination with holographic glutamate uncaging,
      we demonstrate focal, layered modules, in which ventromedial V3 INs form synapses
      with one another and with ventrolateral V3 INs, which in turn form synapses with
      ipsilateral motoneurons. Motoneurons, in turn, provide recurrent excitatory,
      glutamatergic input to V3 INs. Thus, ventral V3 interneurons form layered
      microcircuits that could function to ensure well-timed, spatially specific
      movements.

PMID- 30282026
TI  - Activity-Dependent Netrin-1 Secretion Drives Synaptic Insertion of GluA1
      Containing AMPA Receptors in the Hippocampus.
AB  - Dynamic trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      glutamate receptors (AMPARs) to synapses is critical for activity-dependent
      synaptic plasticity underlying learning and memory, but the identity of key
      molecular effectors remains elusive. Here, we demonstrate that membrane
      depolarization and N-methyl-D-aspartate receptor (NMDAR) activation triggers
      secretion of the chemotropic guidance cue netrin-1 from dendrites. Using
      selective genetic deletion, we show that netrin-1 expression by excitatory
      neurons is required for NMDAR-dependent long-term potentiation (LTP) in the adult
      hippocampus. Furthermore, we demonstrate that application of exogenous netrin-1
      is sufficient to trigger the potentiation of excitatory glutamatergic
      transmission at hippocampal Schaffer collateral synapses via Ca2+-dependent
      recruitment of GluA1-containing AMPARs, promoting the maturation of immature or
      nascent synapses. These findings identify a central role for activity-dependent
      release of netrin-1 as a critical effector of synaptic plasticity in the adult
      hippocampus.

PMID- 30282027
TI  - Cell Aggregation Culture Induces Functional Differentiation of Induced Hepatocyte
      like Cells through Activation of Hippo Signaling.
AB  - Recent progress in direct lineage reprogramming has enabled the generation of
      induced hepatocyte-like (iHep) cells and revealed their potential as an
      alternative to hepatocytes for medical applications. However, the hepatic
      functions of iHep cells are insufficient compared with those of primary
      hepatocytes. Here, we show that cell-aggregate formation can rapidly induce
      growth arrest and hepatic maturation of iHep cells through activation of Hippo
      signaling. During formation of iHep cell aggregates, Yap inactivation is induced
      by actin reorganization and intercellular adhesion, leading to upregulation of
      Hnf1alpha expression in the absence of the Yap/Tead/Chd4 transcriptional
      repressor unit. Hnf1alpha then acts as a central transcription factor that
      regulates liver-enriched gene expression in iHep cell aggregates and induces
      functional differentiation of iHep cells. Moreover, iHep cell aggregates
      efficiently reconstitute injured liver tissues and support hepatic function after
      transplantation. Thus, iHep cell aggregates may provide insights into basic
      research and potential therapies for liver diseases.

PMID- 30282028
TI  - Blimp-1 Functions as a Molecular Switch to Prevent Inflammatory Activity in
      Foxp3+RORgammat+ Regulatory T Cells.
AB  - Foxp3+ regulatory T cells (Treg) are essential modulators of immune responses,
      but the molecular mechanisms underlying their function are not fully understood.
      Here we show that the transcription factor Blimp-1 is a crucial regulator of the
      Foxp3+RORgammat+ Treg subset. The intrinsic expression of Blimp-1 in these cells
      is required to prevent production of Th17-associated cytokines. Direct binding of
      Blimp-1 to the Il17 locus in Treg is associated with inhibitory histone
      modifications but unaltered binding of RORgammat. In the absence of Blimp-1, the
      Il17 locus is activated, with increased occupancy of the co-activator p300 and
      abundant binding of the transcriptional regulator IRF4, which is required, along
      with RORgammat, for IL-17 expression in the absence of Blimp-1. We also show that
      despite their sustained expression of Foxp3, Blimp-1-/- RORgammat+IL-17-producing
      Treg lose suppressor function and can promote intestinal inflammation, indicating
      that repression of Th17-associated cytokines by Blimp-1 is a crucial requirement
      for RORgammat+ Treg function.

PMID- 30282031
TI  - Interplay between Ciliary Ultrastructure and IFT-Train Dynamics Revealed by
      Single-Molecule Super-resolution Imaging.
AB  - Cilia are built and maintained by intraflagellar transport (IFT), driving IFT
      trains back and forth along the ciliary axoneme. How IFT brings about the
      intricate ciliary structure and how this structure affects IFT are not well
      understood. We identify, using single-molecule super-resolution imaging of IFT
      components in living C. elegans, ciliary subdomains, enabling correlation of IFT
      train dynamics to ciliary ultra-structure. In the transition zone, IFT dynamics
      are impaired, resulting in frequent pauses. At the ciliary base and tip, IFT
      trains show intriguing turnaround dynamics. Surprisingly, deletion of IFT motor
      kinesin-II not only affects IFT-train dynamics but also alters ciliary structure.
      Super-resolution imaging in these mutant animals suggests that the arrangement of
      IFT trains with respect to the axonemal microtubules is different than in wild
      type animals. Our results reveal a complex, mutual interplay between ciliary
      ultrastructure and IFT-train dynamics, highlighting the importance of physical
      cues in the control of IFT dynamics.

PMID- 30282029
TI  - Maintenance of Proteostasis by P Body-Mediated Regulation of eIF4E Availability
      during Aging in Caenorhabditis elegans.
AB  - Aging is accompanied by a pervasive collapse of proteostasis, while reducing
      general protein synthesis promotes longevity across taxa. Here, we show that the
      eIF4E isoform IFE-2 is increasingly sequestered in mRNA processing (P) bodies
      during aging and upon stress in Caenorhabditis elegans. Loss of the enhancer of
      mRNA decapping EDC-3 causes further entrapment of IFE-2 in P bodies and lowers
      protein synthesis rates in somatic tissues. Animals lacking EDC-3 are long lived
      and stress resistant, congruent with IFE-2-deficient mutants. Notably, neuron
      specific expression of EDC-3 is sufficient to reverse lifespan extension, while
      sequestration of IFE-2 in neuronal P bodies counteracts age-related neuronal
      decline. The effects of mRNA decapping deficiency on stress resistance and
      longevity are orchestrated by a multimodal stress response involving the
      transcription factor SKN-1, which mediates lifespan extension upon reduced
      protein synthesis. Our findings elucidate a mechanism of proteostasis control
      during aging through P body-mediated regulation of protein synthesis in the soma.

PMID- 30282030
TI  - XBP1-KLF9 Axis Acts as a Molecular Rheostat to Control the Transition from
      Adaptive to Cytotoxic Unfolded Protein Response.
AB  - Transcription factor XBP1s, activated by endoplasmic reticulum (ER) stress in a
      dose-dependent manner, plays a central role in adaptive unfolded protein response
      (UPR) via direct activation of multiple genes controlling protein refolding.
      Here, we report that elevation of ER stress above a critical threshold causes
      accumulation of XBP1s protein sufficient for binding to the promoter and
      activation of a gene encoding a transcription factor KLF9. In comparison to other
      XBP1s targets, KLF9 promoter contains an evolutionary conserved lower-affinity
      binding site that requires higher amounts of XBP1s for activation. In turn, KLF9
      induces expression of two regulators of ER calcium storage, TMEM38B and ITPR1,
      facilitating additional calcium release from ER, exacerbation of ER stress, and
      cell death. Accordingly, Klf9 deficiency attenuates tunicamycin-induced ER stress
      in mouse liver. These data reveal a role for XBP1s in cytotoxic UPR and provide
      insights into mechanisms of life-or-death decisions in cells under ER stress.

PMID- 30282032
TI  - Endogenous rRNA Sequence Variation Can Regulate Stress Response Gene Expression
      and Phenotype.
AB  - Prevailing dogma holds that ribosomes are uniform in composition and function.
      Here, we show that nutrient limitation-induced stress in E. coli changes the
      relative expression of rDNA operons to alter the rRNA composition within the
      actively translating ribosome pool. The most upregulated operon encodes the
      unique 16S rRNA, rrsH, distinguished by conserved sequence variation within the
      small ribosomal subunit. rrsH-bearing ribosomes affect the expression of
      functionally coherent gene sets and alter the levels of the RpoS sigma factor,
      the master regulator of the general stress response. These impacts are associated
      with phenotypic changes in antibiotic sensitivity, biofilm formation, and cell
      motility and are regulated by stress response proteins, RelA and RelE, as well as
      the metabolic enzyme and virulence-associated protein, AdhE. These findings
      establish that endogenously encoded, naturally occurring rRNA sequence variation
      can modulate ribosome function, central aspects of gene expression regulation,
      and cellular physiology.

PMID- 30282033
TI  - Evolutionary Capacitance Emerges Spontaneously during Adaptation to Environmental
      Changes.
AB  - All biological populations are to a greater or lesser degree evolvable, but the
      forces that shape evolvability, especially the evolution of evolvability as an
      adaptive response to pressure to evolve rapidly, are a source of controversy. One
      determinant of evolvability is the set of possible mutations available to a
      genotype, or "mutational neighborhood." A benign (instead of deleterious)
      mutational neighborhood can enhance evolvability. Whether selection for
      evolvability itself can result in a more benign mutational neighborhood remains
      an open question. We document the evolution of increased evolvability in a
      fluctuating environment despite using a regime that precludes, by design, the
      adaptive evolution of evolvability. Instead, a benign mutational neighborhood
      arises as a byproduct of transiently elevated error rates via a mechanism that we
      call emergent evolutionary capacitance. This is evolutionary capacitance similar
      to that seen in a model system for capacitance, the yeast prion [PSI+], but
      without a capacitor.

PMID- 30282036
TI  - Smed-myb-1 Specifies Early Temporal Identity during Planarian Epidermal
      Differentiation.
AB  - The planarian epidermis provides an excellent model to explore adult stem cell
      (ASC) lineage development due to well-characterized and distinct spatiotemporal
      phases during lineage progression. Using flow cytometry-isolated cells enriched
      in epidermal progenitors, we performed transcriptional profiling and RNAi
      screening to uncover regulators of epidermal differentiation. We identified a MYB
      type transcription factor (Smed-myb-1) required for the specification of the
      first temporal phase of post-mitotic maturation. Knockdown of myb-1 abolished the
      early progenitor phase of differentiation without ceasing production of
      subsequent epidermal progenitor states or homeostatic turnover and regeneration
      of the epidermis. Further examination revealed accelerated maturation of ASC
      descendants, with premature entry into subsequent progeny phases and, ultimately,
      the epidermis. These results demonstrate that a spatiotemporal shift in lineage
      progression occurs in the absence of the early progenitor state after myb-1 RNAi,
      and identify myb-1 as a critical regulator of the early temporal window in
      stepwise specification during planarian epidermal differentiation.

PMID- 30282035
TI  - DET1 and COP1 Modulate the Coordination of Growth and Immunity in Response to Key
      Seasonal Signals in Arabidopsis.
AB  - Plant growth and development and outcomes of plant-microbe interactions are
      defined by coordinated responses to seasonal signals. The mechanisms that control
      the coordinated regulation of growth and immunity are not well understood. Here,
      we show that a common signaling module integrates environmental signals, such as
      photoperiod and temperature, to regulate the growth-defense balance. Key light
      signaling components De-Etiolated 1 (DET1) and Constitutive Photomorphogenic 1
      (COP1) negatively regulate immunity and are essential for immune modulation by
      photoperiod and temperature. Our results show that this is regulated by the
      transcription factor Phytochrome Interacting Factor 4 (PIF4), suggesting that the
      DET1/COP1-PIF4 module acts as a central hub for the control of growth and
      immunity in response to seasonal signals. These findings provide a regulatory
      framework for environmental signal integration.

PMID- 30282034
TI  - Elongation/Termination Factor Exchange Mediated by PP1 Phosphatase Orchestrates
      Transcription Termination.
AB  - Termination of RNA polymerase II (Pol II) transcription is a key step that is
      important for 3' end formation of functional mRNA, mRNA release, and Pol II
      recycling. Even so, the underlying termination mechanism is not yet understood.
      Here, we demonstrate that the conserved and essential termination factor Seb1 is
      found on Pol II near the end of the RNA exit channel and the Rpb4/7 stalk.
      Furthermore, the Seb1 interaction surface with Pol II largely overlaps with that
      of the elongation factor Spt5. Notably, Seb1 co-transcriptional recruitment is
      dependent on Spt5 dephosphorylation by the conserved PP1 phosphatase Dis2, which
      also dephosphorylates threonine 4 within the Pol II heptad repeated C-terminal
      domain. We propose that Dis2 orchestrates the transition from elongation to
      termination phase during the transcription cycle by mediating elongation to
      termination factor exchange and dephosphorylation of Pol II C-terminal domain.

PMID- 30282037
TI  - Consumption of Mediterranean versus Western Diet Leads to Distinct Mammary Gland
      Microbiome Populations.
AB  - Recent identification of a mammary gland-specific microbiome led to studies
      investigating bacteria populations in breast cancer. Malignant breast tumors have
      lower Lactobacillus abundance compared with benign lesions, implicating
      Lactobacillus as a negative regulator of breast cancer. Diet is a main
      determinant of gut microbial diversity. Whether diet affects breast microbiome
      populations is unknown. In a non-human primate model, we found that consumption
      of a Western or Mediterranean diet modulated mammary gland microbiota and
      metabolite profiles. Mediterranean diet consumption led to increased mammary
      gland Lactobacillus abundance compared with Western diet-fed monkeys. Moreover,
      mammary glands from Mediterranean diet-fed monkeys had higher levels of bile acid
      metabolites and increased bacterial-processed bioactive compounds. These data
      suggest that diet directly influences microbiome populations outside the
      intestinal tract in distal sites such as the mammary gland. Our study
      demonstrates that diet affects the mammary gland microbiome, establishing an
      alternative mechanistic pathway for breast cancer prevention.

PMID- 30282039
TI  - CD8+ T Cell Activation Leads to Constitutive Formation of Liver Tissue-Resident
      Memory T Cells that Seed a Large and Flexible Niche in the Liver.
AB  - Liver tissue-resident memory T (Trm) cells migrate throughout the sinusoids and
      are capable of protecting against malaria sporozoite challenge. To gain an
      understanding of liver Trm cell development, we examined various conditions for
      their formation. Although liver Trm cells were found in naive mice, their
      presence was dictated by antigen specificity and required IL-15. Liver Trm cells
      also formed after adoptive transfer of in vitro-activated but not naive CD8+ T
      cells, indicating that activation was essential but that antigen presentation
      within the liver was not obligatory. These Trm cells patrolled the liver
      sinusoids with a half-life of 36 days and occupied a large niche that could be
      added to sequentially without effect on subsequent Trm cell cohorts. Together,
      our findings indicate that liver Trm cells form as a normal consequence of CD8+ T
      cell activation during essentially any infection but that inflammatory and
      antigenic signals preferentially tailor their development.

PMID- 30282041
TI  - IFIT1 Exerts Opposing Regulatory Effects on the Inflammatory and Interferon Gene
      Programs in LPS-Activated Human Macrophages.
AB  - Activation of the TLR4 signaling pathway by lipopolysaccharide (LPS) leads to
      induction of both inflammatory and interferon-stimulated genes, but the
      mechanisms through which these coordinately activated transcriptional programs
      are balanced to promote an optimal innate immune response remain poorly
      understood. In a genome-wide small interfering RNA (siRNA) screen of the LPS
      induced tumor necrosis factor alpha (TNF-alpha) response in macrophages, we
      identify the interferon-stimulated protein IFIT1 as a negative regulator of the
      inflammatory gene program. Transcriptional profiling further identifies a
      positive regulatory role for IFIT1 in type I interferon expression, implicating
      IFIT1 as a reciprocal modulator of LPS-induced gene classes. We demonstrate that
      these effects of IFIT1 are mediated through modulation of a Sin3A-HDAC2
      transcriptional regulatory complex at LPS-induced gene loci. Beyond the well
      studied role of cytosolic IFIT1 in restricting viral replication, our data
      demonstrate a function for nuclear IFIT1 in differential transcriptional
      regulation of separate branches of the LPS-induced gene program.

PMID- 30282038
TI  - Two Faces of CwlM, an Essential PknB Substrate, in Mycobacterium tuberculosis.
AB  - Tuberculosis claims >1 million lives annually, and its causative agent
      Mycobacterium tuberculosis is a highly successful pathogen. Protein kinase B
      (PknB) is reported to be critical for mycobacterial growth. Here, we demonstrate
      that PknB-depleted M. tuberculosis can replicate normally and can synthesize
      peptidoglycan in an osmoprotective medium. Comparative phosphoproteomics of PknB
      producing and PknB-depleted mycobacteria identify CwlM, an essential regulator of
      peptidoglycan synthesis, as a major PknB substrate. Our complementation studies
      of a cwlM mutant of M. tuberculosis support CwlM phosphorylation as a likely
      molecular basis for PknB being essential for mycobacterial growth. We demonstrate
      that growing mycobacteria produce two forms of CwlM: a non-phosphorylated
      membrane-associated form and a PknB-phosphorylated cytoplasmic form. Furthermore,
      we show that the partner proteins for the phosphorylated and non-phosphorylated
      forms of CwlM are FhaA, a fork head-associated domain protein, and MurJ, a
      proposed lipid II flippase, respectively. From our results, we propose a model in
      which CwlM potentially regulates both the biosynthesis of peptidoglycan
      precursors and their transport across the cytoplasmic membrane.

PMID- 30282040
TI  - The Kinase Activity of Hematopoietic Progenitor Kinase 1 Is Essential for the
      Regulation of T Cell Function.
AB  - We examined hematopoietic protein kinase 1 (HPK1), whose reliance on scaffold
      versus kinase functions for negative immune cell regulation is poorly understood
      and critical to its assessment as a viable drug target. We identify kinase
      dependent roles for HPK1 in CD8 T cells that restrict their anti-viral and anti
      tumor responses by using HPK1 kinase-dead (HPK1.kd) knockin mice. Loss of HPK1
      kinase function enhanced T cell receptor signaling and cytokine secretion in a T
      cell-intrinsic manner. In response to chronic lymphocytic choriomeningitis virus
      (LCMV) infection or tumor challenge, viral clearance and tumor growth inhibition
      were enhanced in HPK1.kd mice, accompanied by an increase in effector CD8 T cell
      function. Co-blockade of PD-L1 further enhanced T effector cell function,
      resulting in superior anti-viral and anti-tumor immunity over single target
      blockade. These results identify the importance of HPK1 kinase activity in the
      negative regulation of CD8 effector functions, implicating its potential as a
      cancer immunotherapy target.

PMID- 30282043
TI  - Distinct Hypothalamic and Brainstem Contributions to Lorcaserin Action.
AB  - Pro-opiomelanocortin (POMC)-expressing neurons regulate energy balance and
      mediate the effects of some classes of anti-obesity therapeutics. In this issue
      of Cell Metabolism, D'Agostino et al. (2018) demonstrate that a small and often
      overlooked population of POMC neurons in the brainstem contributes to satiation
      induced by the FDA-approved drug lorcaserin.

PMID- 30282042
TI  - Removal of hERG potassium channel affinity through introduction of an oxygen
      atom: Molecular insights from structure-activity relationships of strychnine and
      its analogs.
AB  - Nux vomica has been effectively used in Traditional Chinese Medicine. The
      processing of Nux vomica is necessary to reduce toxicity before it can be used in
      clinical practice. However, the mechanism for processing detoxification is
      unclear. hERG channels have been subjected to a routine test for compound cardiac
      toxicity in the drug development process. Therefore, we examined the effects and
      mechanisms of strychnine and brucine, two main ingredients of Nux vomica, and
      their N-oxides on hERG channels. Strychnine and brucine exhibited concentration
      dependent inhibition of hERG channels with IC50 values of 25.9 MUM and 44.18 MUM,
      respectively. However, their nitrogen oxidative derivatives produced by
      processing of Nux vomica, strychnine N-oxide and brucine N-oxide, lost their
      activity on hERG channels. Compared to their parent compounds, only an oxygen
      atom was introduced in the nitrogen oxidative isoforms to compensate for the N+ -
      charge, suggesting that the protonated nitrogen is the key group for strychnine
      and brucine binding to hERG channel. Alanine-mutagenesis identified Y652 is the
      most important residue for strychnine and brucine binding to hERG channel. Y652A
      mutation increased the IC50 for strychnine and brucine by 21.64-fold and 29.78
      fold that of WT IhERG, respectively. Docking simulations suggested that the
      protonated nitrogen of strychnine and brucine formed a cation-pi interaction with
      the aromatic ring of Y652. This study suggests that introduction of an oxygen to
      compensate for the N+ - charge could be a useful strategy for reducing hERG
      potency and increasing the safety margin of alkaloid-type compounds in drug
      development.

PMID- 30282044
TI  - AMPK Regulates the Epigenome through Phosphorylation of TET2.
AB  - Emerging evidence suggests that changes to cellular metabolism can regulate
      epigenetic modifications to alter gene expression. Recently in Nature, Wu et al.
      show that the metabolic regulator AMPK can phosphorylate and thus stabilize the
      epigenetic modifying enzyme TET2, defining a novel signaling link between
      metabolism and the epigenome.

PMID- 30282045
TI  - Shipping Calpastatin to the Rescue: Prevention of Neuromuscular Degeneration
      through Mitofusin 2.
AB  - How neuromuscular junctions (NMJs) are lost in disease and aging is unclear.
      Recently in Cell Metabolism, Wang et al. (2018) discovered that endoplasmic
      reticulum-mitochondria tethering by Mitofusin 2 is required to organize a cleft
      between these two organelles, which, like a lorry, traffics down the axon to
      distribute calpastatin to terminals where it blocks NMJ degradation.

PMID- 30282046
TI  - Fatty Acid Oxidation in Macrophages and T Cells: Time for Reassessment?
AB  - Previous immunometabolism research using the CPT1 inhibitor etomoxir suggests
      that long-chain fatty acid oxidation (LC-FAO) supports IL-4-driven alternative
      macrophage activation (M(IL-4)) and regulates memory and regulatory T cell
      formation. Divakaruni et al. (2018) and Raud et al. (2018) now report that LC-FAO
      is largely dispensable for these processes.

PMID- 30282047
TI  - Remission of Human Type 2 Diabetes Requires Decrease in Liver and Pancreas Fat
      Content but Is Dependent upon Capacity for beta Cell Recovery.

PMID- 30282048
TI  - The ocular surface in children: A review of current knowledge and meta-analysis
      of tear film stability and tear secretion in children.
AB  - PURPOSE: A review of ocular surface and meta-analysis of tear stability (tear
      break up time, TBUT) and tear secretion (Schirmer test) values in healthy
      children was conducted. METHODS: Articles published between 1996 and 2017 indexed
      on MEDLINE, PubMed, Embase, Scopus and Google scholar were retrieved using
      defined search terms. Statistical analysis (including sensitivity analysis and
      meta regression) was performed. RESULTS: 23 studies were summarised (5291
      neonates (0-29 days), infants (1 month-1 year) or children (1-18 years)) and a
      meta-analysis conducted using 15 eligible studies (1077 participants). The
      combined mean TBUT in children was 14.64 s (s) (95% CI, 11.64, 17.64) and 21.76 s
      (95% CI, 20.43, 23.09) for sodium fluorescein TBUT and non-invasive TBUT
      respectively (NIBUT). The combined mean NIBUT was 32.5 s (95% CI, 31.78-33.22) in
      neonates. The combined mean Schirmer I with and without anesthesia were 16.26
      mm/5 min (95% CI, 13.17, 19.36) and 29.30 mm/5 min (95% CI, 27.65, 30.96) in
      children and 9.36 mm/5 min (95% CI, 6.54, 12.18) and 17.63 mm/5 min (95% CI,
      12.03, 23.23) in neonates. Meta regression showed a significantly lower TBUT in
      children from studies conducted in Asia (p = 0.004). CONCLUSION: There is paucity
      of data on ocular surface variables in healthy children, making it difficult to
      draw valid comparisons with adult values.

PMID- 30282049
TI  - Vibration spectroscopy and body biofluids: Literature review for clinical
      applications.
AB  - Vibrational spectroscopy techniques such as Raman and IR (infrared) allow real
      time, non-invasive and non-destructive analysis of organic compounds with a good
      limit-of-detection. This review aims to show the progress of clinical diagnosis
      and prognosis due to advances of vibrational spectroscopy techniques in biofluids
      through an extensive literature review. This review was performed by searching
      for studies using the keywords "biofluids or biological fluids" and "diagnostic
      techniques" in PubMed, Scopus and Google Scholar. We found 580 articles in the
      1990s, 1171 articles in the 2000s and 1688 in the years from 2011. Also, a second
      search including "biofluids or biological fluids" and "vibrational spectroscopy"
      returned only one article in the 1990s, three papers in the 2000s and 18 in the
      years from 2011.This growth suggests a great potential of biofluid research using
      vibrational spectroscopy. Sample collection variations(quantity and
      contaminations due to contact with other body parts and their secretions) are
      important factors that influence sample composition. Once these factors are taken
      into account, spectroscopic analysis may provide the necessary information to
      identify a disease, lesion, tumor or infection. With the present review we aim to
      encourage the study of vibrational spectroscopy techniques for analysis of
      biofluids focusing in clinical applications. In the future, it will widely
      benefit clinicians, allowing new diagnostic approaches, and for patients to have
      early diagnosis for most every disease.

PMID- 30282050
TI  - Proteomic changes in Arthrobotrys oligospora conidia in response to benzaldehyde
      induced fungistatic stress.
AB  - Soil fungistasis limits the effect of fungal agents designed to control plant
      parasitic nematodes. Benzaldehyde is a fungistatic factor produced by soil
      microorganisms that can suppress conidial germination, but the molecular
      mechanism of this suppression is unknown. In this study, three conidial proteomes
      of Arthrobotrys oligospora ATCC24927, a nematode-trapping fungus, were obtained,
      quantified, and compared. Under benzaldehyde fungistatic stress, conidial protein
      expression profile changed significantly. Screening with a twofold selection
      criterion revealed 164 up-regulated and 110 down-regulated proteins. 17 proteins
      related to protein translation were down-regulated and gene transcription
      analysis suggested that the repression of proteins translation might be one
      mechanism by which benzaldehyde inhibites conidial germination. Benzaldehyde also
      resulted in the down-regulation of respiratory chain proteins and mitochondrial
      processes, as well as the repression of conidial DNA synthesis. In addition, the
      conidia up-regulated several proteins that enable it to resist benzaldehyde
      induced fungistatis, and this was confirmed by a functional assessment of two
      knockout mutants. This study reveals putative mechanisms by which benzaldehyde
      causes fungistasis as well as the proteomic response of conidia to benzaldehyde.
      SIGNIFICANCE: Soil fungistasis limits the effect of fungal agents designed to
      control plant-parasitic nematodes. Benzaldehyde is one of fungistatic factors
      produced by soil microorganisms that can suppress conidial germination. In this
      study, we found that conidial protein expression profile changed significantly
      under benzaldehyde fungistatic stress. This research revealed new mechanistic
      data that describe how benzaldehyde is responsible for fungiststis by inhibiting
      conidial germination. Moreover, we also found that conidia can resist
      benzaldehyde by up-regulating proteins such as benzaldehyde dehydrogenase and
      heat shock proteins. This study also showed that proteomics methods play
      important roles in addressing soil fungistatic mechanisms.

PMID- 30282051
TI  - Exome sequencing confirms diagnosis of kabuki syndrome in an-adult with hodgkin
      lymphoma and unusually severe multisystem phenotype.
AB  - We report a 34-year-old male patient with a novel variant in KMT2D gene, which
      finally ended a quest for a diagnosis that was clinically suspected in the past,
      prior the molecular basis of Kabuki Syndrome (KS) was known. The patient
      showcases the multisystemic features, with involvement of all previously
      associated with KS body systems, presence of immune deficiency as well as
      autoimmune disorders, requiring three pancreatic transplants. We also report, for
      the first time to our knowledge, the presence of epidural lipomatosis and Hodgkin
      Lymphoma in a patient with KS.

PMID- 30282052
TI  - Micro-patterned endogenous stroma equivalent induces polarized crypt-villus
      architecture of human small intestinal epithelium.
AB  - The small intestine is the major site for digestion, drug and nutrient
      absorption, as well as a primary site for many diseases. Current in vitro gut
      models fail in reproducing the complex intestinal extracellular matrix (ECM)
      network of the lamina propria and the peculiar architecture of the crypt-villus
      axis. Here we proposed a novel in vitro human intestine model that mimics the
      intestinal stromal topography and composition and strictly reproduces the tissue
      polarity with the crypt-villus architecture. First we developed a 3D human
      intestinal stromal equivalent (3D-ISE) composed of human intestinal subepithelial
      myofibroblasts (ISEMFs) embedded in their own extracellular matrix. Then, we
      seeded human colon carcinoma-derived cells (Caco-2) onto flat or patterned cell
      synthetized stromal equivalent structure and cultured them until the formation of
      a well-oriented epithelium. We demonstrated that the patterned stroma increases
      the absorbing surface area, the epithelial proliferation rate, and the density of
      microvilli. In addition it induces changes in the biological functions of the
      epithelial cells such as enzymes and mucus production, polarization and tightness
      showing a physiological cell-lineage compartmentalization along the crypt/villi
      axes with the undifferentiated phenotypes at the base. At last, we reproduced an
      inflamed intestinal tissue model in which we identified the contribution of the
      stromal microenvironment by molecular (cytokines release and MMPs production) and
      immunofluorescence analyses and the effects of the epithelial-stromal cross-talk
      in the intestinal innate immunity by multiphoton investigation that revealed
      differences in the collagen network architecture. STATEMENT OF SIGNIFICANCE: The
      intestinal stroma morphology and composition has a fundamental role in crypt
      villus development and appropriate epithelial cell-lineage compartmentalization.
      On this base, here we develop an engineered organotypic model of human intestine
      equivalent in which a functional epithelial/ECM crosstalk is recapitulated. Due
      to its accessible luminal surface it provides a new platform for preclinical
      studies of mucosal immunology and bowel inflammation as well as the assessment of
      pharmaco-toxicity studies.

PMID- 30282053
TI  - Control of mRNA splicing by noncoding intragenic RNA elements that evoke a
      cellular stress response.
AB  - Once activated by double-helical RNA, mammalian RNA-dependent stress protein
      kinase, PKR, phosphorylates its substrate, translation initiation factor
      eIF2alpha, to inhibit translation. eIF2alpha phosphorylation is critical for
      mounting a cellular stress response. We describe short, 100-200 nucleotide
      elements within cellular genes that, once transcribed, form RNA structures that
      potently activate PKR in the vicinity of the RNA and thereby tightly regulate
      gene expression in cis. Intragenic RNA activators of PKR can (a) attenuate
      translation of the encoded mRNA by activating PKR and inducing eIF2alpha
      phosphorylation, exemplified by the IFN-gamma gene, or (b) greatly enhance mRNA
      splicing efficiency by activating PKR and inducing nuclear eIF2alpha
      phosphorylation, thus enabling efficient early spliceosome assembly, exemplified
      by the adult and fetal globin genes and the TNF-alpha gene that activates PKR
      through an RNA pseudoknot conserved from fish to humans. These opposite outcomes
      considerably extend the potential scope of gene regulation by these novel RNA
      elements.

PMID- 30282054
TI  - Connected toothbrush, augmented reality and oral hygiene in children with cleft
      lip and palate.

PMID- 30282055
TI  - Vitamin D and omega-3 trial to prevent and treat diabetic kidney disease:
      Rationale, design, and baseline characteristics.
AB  - Diabetic kidney disease (DKD), defined as reduced glomerular filtration rate
      (GFR), elevated urine albumin excretion, or both that is clinically attributable
      to diabetes, is a common and morbid diabetes complication. Animal-experimental
      data, observational human studies, and short-term clinical trials suggest that
      vitamin D and omega-3 fatty acid supplements may be safe and inexpensive
      interventions to reduce the incidence and progression of DKD. The Vitamin D and
      Omega-3 Trial to Prevent and Treat DKD (VITAL-DKD) was designed as an ancillary
      study to the VITAL trial of 25,871 US adults. In a 2 * 2 factorial design, VITAL
      participants were randomly assigned to vitamin D3 (cholecalciferol, 2000 IU
      daily) or placebo and to marine omega-3 fatty acids (eicospentaenoic acid and
      docosahexaenoic acid, 1 g/d) or placebo. VITAL-DKD enrolled a subset of 1326
      VITAL participants with type 2 diabetes at baseline to test the effects of
      vitamin D and omega-3 fatty acids on changes in estimated GFR and urine albumin
      excretion. Over five years of follow-up, VITAL-DKD collected blood and urine
      samples to quantify changes in estimated GFR (the primary study outcome) and
      urine albumin excretion. At baseline, mean age of VITAL-DKD participants was 67.6
      years, 46% were women, 30% were of racial or ethnic minority, and the prevalence
      of DKD (estimated GFR <60 mL/min/1.73m2 or urine albumin-creatinine ratio >= 30
      mg/g) was 17%. In this type 2 diabetes population, VITAL-DKD will test the
      hypotheses that vitamin D and omega-3 fatty acids help prevent the development
      and progression of DKD.

PMID- 30282057
TI  - Alendronate improves bone density and type I collagen accumulation but increases
      the amount of pentosidine in the healing dental alveolus of ovariectomized
      rabbits.
AB  - BACKGROUND: It has been shown that the oral aminobisphosphonate sodium
      alendronate (ALN) therapy reduces the risk of main fractures in osteoporotic
      women, but its effect on the jaw bones is poorly known. Here, we hypothesized
      that ALN affects the newly formed alveolar bone, particularly the quality of the
      type I collagen cross-linking. METHODS: Osteoporosis was induced by ovariectomy
      (OVX) in 6-month old rabbits. Six weeks following surgery, eight animals were
      treated by oral gavage with ALN (OVX + ALN) and ten received placebo (OVX + Pbo).
      Another six rabbits which were sham operated also received placebo (SHAM + Pbo).
      One month following the beginning of treatment, the upper and lower left first
      premolars were removed. Six weeks later, the upper and the lower right first
      premolars were also extracted. One month after the second extraction, biopsies
      were collected from the maxillary extraction sites and collagen crosslinks were
      analyzed in the newly formed bone tissue by HPLC. Also, at this time, mandibular
      bone segments were subjected to MUCT. RESULTS: Animals treated with ALN achieved
      a roughly 2-time greater bone volume fraction value at a late healing period than
      animals in the other groups (p < 0.05). Collagen mean results were 2- to 4-times
      superior in the OVX + ALN group than in the control groups (p < 0.05). ALN
      treated animals presented higher amounts of the non-enzymatic collagen cross-link
      pentosidine (PEN) than the sham-operated rabbits (p < 0.05), whereas the OVX +
      Pbo group presented the highest amount of PEN (p < 0.05). CONCLUSION: Alendronate
      increases bone volume and collagen accumulation, but does not fully rescue the
      non-osteoporotic alveolar tissue quality as is evident from the increased
      quantity of pentosidine.

PMID- 30282056
TI  - Community Study of Outcome Monitoring for Emotional Disorders in Teens (COMET): A
      comparative effectiveness trial of a transdiagnostic treatment and a measurement
      feedback system.
AB  - Emotional disorders, encompassing a range of anxiety and depressive disorders,
      are the most prevalent and comorbid psychiatric disorders in adolescence.
      Unfortunately, evidence-based psychosocial therapies typically focus on single
      disorders, are rarely adopted by community mental health center clinicians, and
      effect sizes are modest. This article describes the protocol for a comparative
      effectiveness study of two novel interventions designed to address these
      challenges. The first intervention is a transdiagnostic treatment (the Unified
      Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents, UP
      A), a promising new approach that uses a small number of common strategies to
      treat a broad range of emotional disorders, and their underlying shared emotional
      vulnerabilities. The second intervention is a standardized measurement feedback
      system, the Youth Outcomes Questionnaire (YOQ), designed to improve clinical
      decision making using weekly symptom and relational data. The three study arms
      are treatment as usual (TAU), TAU plus the YOQ (TAU+), and UP-A (used in
      combination with the YOQ). The primary aims of the study are to [1] compare the
      effects of the UP-A and TAU+ to TAU in community mental health clinics, [2] to
      isolate the effects of measurement and feedback by comparing the UP-A and TAU+
      condition, and [3] to examine the mechanisms of action of both interventions.
      Design considerations and study methods are provided to inform future
      effectiveness research.

PMID- 30282058
TI  - Understanding the severity of depression: Which symptoms of depression are the
      best indicators of depression severity?
AB  - BACKGROUND: In DSM-5, all symptoms of depression are considered equal
      representations of severity. In ICD-10, the type of symptom is considered in
      classifying severity. It is important to better understand if the defining
      symptoms of depression are differentially associated with overall severity so
      that severity categorization in diagnostic systems is most valid. In the present
      study from the Rhode Island Methods to Improve Diagnostic Assessment and Services
      (MIDAS) project we examined the association between the individual diagnostic
      criteria for major depressive disorder (MDD) and global ratings of depression
      severity. We thus examined whether there is support for the ICD-10 approach in
      which some symptoms are better indicators of severity than are other symptoms.
      METHODS: Patients were evaluated with a semi-structured interview and the
      presence of each symptom of MDD was recorded. Patients were also rated on the
      Clinical Global Index of severity (CGI-S). RESULTS: All 9 DSM-5 criteria were
      significantly correlated with the CGI with suicidality having the highest
      correlation. A regression analysis found that all 9 criteria were significant
      predictors of the CGI. At the symptom level, 15 of the 17 symptoms were
      significantly correlated with the CGI (all except increased appetite and
      increased weight). DISCUSSION: There were differences between the symptoms of
      depression in their association with severity with suicidal ideation, depressed
      mood, and anhedonia having the highest correlations with severity whereas some
      symptoms were not significantly associated with severity distinctions. Future
      descriptions of the severity of depression should not consider all criteria as
      equal representations of severity.

PMID- 30282059
TI  - Contribution of stress and coping strategies to problematic Internet use in
      patients with schizophrenia spectrum disorders.
AB  - INTRODUCTION: Internet use is already high and increasing rapidly among people
      with psychotic disorders, but there have been few studies on problematic Internet
      use (PIU) among patients with schizophrenia spectrum disorders. This study aimed
      to measure the prevalence of PIU and identify the factors associated with PIU
      among patients with schizophrenia spectrum disorders. METHODS: A cross-sectional
      survey was performed that included 368 outpatients with schizophrenia spectrum
      disorders: 317 with schizophrenia, 22 with schizoaffective disorder, 9 with
      schizophreniform disorder, and 20 with other schizophrenia spectrum and psychotic
      disorders. The severity of psychotic symptoms and levels of personal and social
      functioning were assessed by the Clinician-rated Dimensions of Psychosis Symptom
      Severity (CRDPSS) scale and the Personal and Social Performance (PSP) scale,
      respectively. PIU was evaluated using Young's Internet Addiction Test (IAT).
      Additionally, the Hospital Anxiety and Depression Scale (HADS), Perceived Stress
      Scale (PSS), Rosenberg Selfesteem Scale (RSES), and Brief Coping Orientation to
      Problems Experienced (COPE) Inventory were administered. RESULTS: PIU was
      identified in 81 (22.0%) of the 368 patients with schizophrenia spectrum
      disorders. Subjects with PIU were significantly younger and more likely to be
      male. Scores on the HADS, PSS, and dysfunctional coping dimension of the Brief
      COPE Inventory were significantly higher, and RSES scores were significantly
      lower, in the PIU group. Logistic regression analysis indicated that PIU in
      patients was significantly associated with scores on the PSS and dysfunctional
      coping dimension of the Brief COPE Inventory. CONCLUSIONS: Patients with
      schizophrenia spectrum disorders and PIU were significantly more likely to have
      high levels of perceived stress and dysfunctional coping strategies. Patients
      with schizophrenia spectrum disorders who also engage in PIU may benefit from
      interventions that help them to develop appropriate skills for coping with
      stress.

PMID- 30282060
TI  - A correlative approach, combining chlorophyll a fluorescence, reflectance, and
      Raman spectroscopy, for monitoring hydration induced changes in Antarctic lichen
      Dermatocarpon polyphyllizum.
AB  - Lichens are successful colonizers in extreme environments worldwide, and they are
      considered to have played an important role during the evolution of life. Here,
      we have used a correlative approach, combining three optical signals (chlorophyll
      a fluorescence (ChlF), reflectance, and Raman spectra), to monitor hydration
      induced changes in photosynthetic properties of an Antarctic chlorolichen
      Dermatocarpon polyphyllizum. We measured these three signals from this lichen at
      different stages (after 4 h, 24 h, and 48 h) of hydration, and compared the data
      obtained from this lichen in "dry state" as well as in different "hydrated
      state". We found that dry state of this lichen has: (1) no variable ChlF, (2)
      high reflectance, with no red-edge and almost zero photochemical reflectance
      index (PRI), and (3) low-intensity Raman bands of their carotenoids. Furthermore,
      4 h of hydration, increased its relative water content (RWC) by 93%, showed red
      edge in reflectance spectra, and changed the maximum quantum yield of PSII
      photochemistry (Fv/Fm) from 0 to 0.57 +/- 0.01. We found that reflectance
      indices, normalized difference index (NDVI) and PRI, significantly differed
      between brown and black/green surface areas, at all hydration stages; whereas, a
      shift in the Raman nu1(CC) band, between brown and black/green surface areas,
      occurred in 24 h or 48 h hydrated samples. These data indicate that hydration
      shortly (within 4 h) activated functions of photosynthetic apparatus, and the de
      novo synthesis of carotenoids occured in 24 h or 48 h. Furthermore, exposure to
      high irradiance (2000 MUmol photons m-2 s-1), in 48 h hydrated lichen,
      significantly reduced Fv/Fm (signifies photoinhibition) and increased PRI
      (represents changes in xanthophyll pigments). We conclude that the implication of
      such a correlative approach is highly useful for understanding survival and
      protective mechanisms on extremophile photosynthetic organisms.

PMID- 30282061
TI  - Joint registration and synthesis using a probabilistic model for alignment of MRI
      and histological sections.
AB  - Nonlinear registration of 2D histological sections with corresponding slices of
      MRI data is a critical step of 3D histology reconstruction algorithms. This
      registration is difficult due to the large differences in image contrast and
      resolution, as well as the complex nonrigid deformations and artefacts produced
      when sectioning the sample and mounting it on the glass slide. It has been shown
      in brain MRI registration that better spatial alignment across modalities can be
      obtained by synthesising one modality from the other and then using intra
      modality registration metrics, rather than by using information theory based
      metrics to solve the problem directly. However, such an approach typically
      requires a database of aligned images from the two modalities, which is very
      difficult to obtain for histology and MRI. Here, we overcome this limitation with
      a probabilistic method that simultaneously solves for deformable registration and
      synthesis directly on the target images, without requiring any training data. The
      method is based on a probabilistic model in which the MRI slice is assumed to be
      a contrast-warped, spatially deformed version of the histological section. We use
      approximate Bayesian inference to iteratively refine the probabilistic estimate
      of the synthesis and the registration, while accounting for each other's
      uncertainty. Moreover, manually placed landmarks can be seamlessly integrated in
      the framework for increased performance and robustness. Experiments on a
      synthetic dataset of MRI slices show that, compared with mutual information based
      registration, the proposed method makes it possible to use a much more flexible
      deformation model in the registration to improve its accuracy, without
      compromising robustness. Moreover, our framework also exploits information in
      manually placed landmarks more efficiently than mutual information: landmarks
      constrain the deformation field in both methods, but in our algorithm, it also
      has a positive effect on the synthesis - which further improves the registration.
      We also show results on two real, publicly available datasets: the Allen and
      BigBrain atlases. In both of them, the proposed method provides a clear
      improvement over mutual information based registration, both qualitatively
      (visual inspection) and quantitatively (registration error measured with pairs of
      manually annotated landmarks).

PMID- 30282062
TI  - Prospects of annular differential phase contrast applied for optical sectioning
      in STEM.
AB  - The annular differential phase contrast (ADPC) mode in a third-order spherical
      aberration-corrected scanning transmission electron microscope (STEM) has
      recently been realized at an operating voltage of 300 kV by inserting a physical
      Fresnel phase plate in front of the objective lens and by using a detector
      geometry which matches that of the Fresnel phase plate [1]. By image calculation
      we explore the feasibility of this mode for the voltage range of 20-80kV.
      Alternatively, we mimic the Fresnel phase plate material-free with the help of
      the adjustable aberrations of the corrector. The additional correction of
      chromatic aberration, fifth-order spherical aberration and image spread improves
      significantly the resolution and contrast. Under these advanced conditions it is
      possible to achieve optical sectioning in the ADPC mode with atomic resolution
      and a depth of field shorter than 3 A for an accelerating voltage of 30 kV.
      Moreover, we show that the contrast obtained in the ADPC mode is clearly superior
      over the contrast in incoherent bright-field (IBF) and high-angle annular dark
      field (HAADF), the two other common methods in STEM. We propose that with the
      advanced ADPC method applied in STEM, the investigation of the inner structure of
      thick samples will be possible without slicing.

PMID- 30282064
TI  - Phenotypic variations in carriers of predicted protein-truncating genetic
      variants in MYBPC3: an autopsy-based case series.
AB  - Our aim is to characterize predicted protein-truncating variants (PTVs) in
      MYBPC3, the gene most commonly associated with hypertrophic cardiomyopathy (HCM),
      found in a series of autopsied HCM cases after sudden unexpected cardiac death.
      All cases underwent death scene investigation, gross and microscopic autopsies,
      toxicological testing, a review of medical records, and a molecular analysis of
      95 cardiac genes. We found four pathogenic PTVs in MYBPC3 among male decedents.
      All variants were previously submitted to ClinVar without phenotype details. Two
      PTVs were located in the cardiac-specific myosin S2-binding (M) motif at the N
      terminus of the MYBPC3-encoded cMyBP-C protein, and two PTVs were in the non
      cardiac-specific C-terminus of the protein. The carriers of two cardiac-specific
      M-motif PTVs died at age 38 years; their heart weight (HW, g) and body mass index
      (BMI, kg/m2) ratio were 34.90 (890/25.5) and 23.56 (980/41.6), respectively. In
      contrast, the carriers of two non-cardiac-specific C-terminal PTVs died at age 57
      and 67 years, respectively; their HW and BMI ratio were 14.71 (450/30.6) and
      13.98 (600/42.9), respectively. A detailed three-generation family study was
      conducted in one case. This study showed age-at-death variations among MYBPC3
      PTVs carriers in adult males.

PMID- 30282063
TI  - Accuracy of different three-dimensional subcortical human brain atlases for DBS 
      lead localisation.
AB  - BACKGROUND: Accurate interindividual comparability of deep brain stimulation
      (DBS) lead locations in relation to the surrounding anatomical structures is of
      eminent importance to define and understand effective stimulation areas. The
      objective of the current work is to compare the accuracy of the DBS lead
      localisation relative to the STN in native space with four recently developed
      three-dimensional subcortical brain atlases in the MNI template space. Accuracy
      is reviewed by anatomical and volumetric analysis as well as intraoperative
      electrophysiological data. METHODS: Postoperative lead localisations of 10
      patients (19 hemispheres) were analysed in each individual patient based on
      Brainlab software (native space) and after normalization into the MNI space and
      application of 4 different human brain atlases using Lead-DBS toolbox within
      Matlab (template space). Each patient's STN was manually segmented and the
      relation between the reconstructed lead and the STN was compared to the 4 atlas
      based STN models by applying the Dice coefficient. The length of intraoperative
      electrophysiological STN activity along different microelectrode recording tracks
      was measured and compared to reconstructions in native and template space.
      Descriptive non-parametric statistical tests were used to calculate differences
      between the 4 different atlases. RESULTS: The mean STN volume of the study cohort
      was 153.3 +/- 40.3 mm3 (n = 19). This is similar to the STN volume of the DISTAL
      atlas (166 mm3; p = .22), but significantly larger compared to the other atlases
      tested in this study. The anatomical overlap of the lead-STN-reconstruction was
      highest for the DISTAL atlas (0.56 +/- 0.18) and lowest for the PD25 atlas (0.34
      +/- 0.17). A total number of 47 MER trajectories through the STN were analysed.
      There was a statistically significant discrepancy of the electrophysiogical STN
      activity compared to the reconstructed STN of all four atlases (p < .0001).
      CONCLUSION: Lead reconstruction after normalization into the MNI template space
      and application of four different atlases led to different results in terms of
      the DBS lead position relative to the STN. Based on electrophysiological and
      imaging data, the DISTAL atlas led to the most accurate display of the
      reconstructed DBS lead relative to the DISTAL-based STN.

PMID- 30282065
TI  - How Long Non-Coding RNAs and MicroRNAs Mediate the Endogenous RNA Network of Head
      and Neck Squamous Cell Carcinoma: a Comprehensive Analysis.
AB  - BACKGROUND/AIMS: Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs
      (ceRNAs) to compete for microRNAs (miRNAs) in cancer metastasis. Head and neck
      squamous cell carcinoma (HNSCC) is one of the most common human cancers and rare
      biomarkers could predict the clinical prognosis of this disease and its
      therapeutic effect. METHODS: Weighted gene co-expression network analysis (WGCNA)
      was performed to identify differentially expressed mRNAs (DEmRNAs) that might be
      key genes. GO enrichment and protein-protein interaction (PPI) analyses were
      performed to identify the principal functions of the DEmRNAs. An lncRNA-miRNA
      mRNA network was constructed to understand the regulatory mechanisms in HNSCC.
      The prognostic signatures of mRNAs, miRNAs, and lncRNAs were determined by Gene
      Expression Profiling Interactive Analysis (GEPIA) and using Kaplan-Meier survival
      curves for patients with lung squamous cell carcinoma. RESULTS: We identified
      2,023 DEmRNAs, 1,048 differentially expressed lncRNAs (DElncRNAs), and 82
      differentially expressed miRNAs (DEmiRNAs). We found that eight DEmRNAs, 53
      DElncRNAs, and 16 DEmiRNAs interacted in the ceRNA network. Three ceRNAs (HCG22,
      LINC00460 and STC2) were significantly correlated with survival. STC2 transcript
      levels were significantly higher in tumour tissues than in normal tissues, and
      the STC2 expression was slightly upregulated at different stages of HNSCC.
      CONCLUSION: LINC00460, HCG22 and STC2 exhibited aberrant levels of expression and
      may participate in the pathogenesis of HNSCC.

PMID- 30282066
TI  - Inhibition of Protein Phosphatase 2A Sensitizes Mucoepidermoid Carcinoma to
      Chemotherapy via the PI3K-AKT Pathway in Response to Insulin Stimulus.
AB  - BACKGROUND/AIMS: Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine
      phosphatase that mediates cell cycle regulation and metabolism. Mounting evidence
      has indicated that PP2A inhibition exhibits considerable anticancer potency in
      multiple types of human cancers. However, the efficacy of PP2A inhibition remains
      unexplored in mucoepidermoid carcinoma (MEC), especially in locally advanced and
      metastatic cases with limited systemic treatment. In this study, we demonstrated
      the therapeutic potency of LB100 in mucoepidermoid carcinoma. METHODS: In this
      study, the expression of PP2A was evaluated using immunohistochemical (IHC)
      staining. The effects associated with LB100 alone and in combination with
      cisplatin for the treatment of mucoepidermoid carcinoma were investigated both in
      vitro, regarding metabolism, proliferation, and migration, and in vivo in a
      mucoepidermoid carcinoma xenograft model. In addition, with LB100 treatment and
      in response to an insulin stimulus, the expression levels and phosphorylation
      levels of targets in the PI3K-AKT pathway were determined using western blot
      analysis and immunoblotting. RESULTS: The expression of protein phosphatase 2A
      was significantly upregulated in the clinical specimens of high-grade MECs
      compared with those of low-/medium-grade MECs and normal controls. In this
      article, we report that a small molecule PP2A inhibitor, LB100, decreased
      cellular viability and glycolytic activity and induced G2/M cell cycle arrest.
      Importantly, LB100 enhanced the efficacy of cisplatin in mucoepidermoid carcinoma
      cells both in vitro and in vivo. PP2A inhibition by LB100 increased the
      phosphorylation of insulin receptor substrate 1(IRS-1) on serine residues,
      downregulated the expression of phosphatidylinositol 3-kinase (PI3K) p110 alpha
      subunit and dephosphorylated AKT at Ser473 and Thr308 in mucoepidermoid carcinoma
      cells in response to insulin stimulus. CONCLUSION: These results highlight the
      translational potential of PP2A inhibition to synergize with cisplatin in
      mucoepidermoid carcinoma treatment.

PMID- 30282067
TI  - Circular RNA Expression Profile in Laryngeal Squamous Cell Carcinoma Revealed by
      Microarray.
AB  - BACKGROUND/AIMS: A growing body of evidence has suggested that circular RNAs
      (circRNAs) have crucial functions in the regulation of gene expression, and their
      dysregulation has been implicated in various types of cancers. However, the roles
      of circRNAs in laryngeal cancer remain largely unknown. This study investigated
      the global changes in the expression pattern of circRNAs in laryngeal squamous
      cell carcinoma (LSCC) to identify potential differentially expressed circRNAs.
      METHODS: Microarray-based circRNA expression was determined in LSCC and paired
      normal laryngeal tissues. Pathway analyses of the genes producing differentially
      expressed circRNAs were performed to predict the function of circRNAs using
      standard enrichment computational methods. Expression levels of candidate
      circRNAs and microRNAs (miRNAs) were detected by quantitative real-time PCR. The
      circRNA/ miRNA interactions were constructed using bioinformatics methods to
      predict the binding of miRNA with circRNA. RESULTS: We identified 506
      differentially expressed circRNAs from human LSCC and normal laryngeal mucosa
      tissues. We confirmed that hsa_circ_0044520 and hsa_circ_0044529 were
      significantly upregulated in LSCC tissues. The most likely potential target
      miRNAs for hsa_ circ_0044520 and hsa_circ_0044529 were hsa-miR-4726-5p and hsa
      miR-4640-5p, respectively. Functional analysis showed that hsa_circ_0044520 and
      hsa_circ_0044529 were involved in the process of collagen synthesis. CONCLUSION:
      Competitive endogenous RNA network prediction and bioinformatics functional
      analysis revealed that hsa_circ_0044520 and hsa_circ_0044529 play important
      regulatory roles by sponging hsa-miR-4726-5p and hsa-miR-4640-5p, thereby
      providing novel insights into the tumorigenesis of LSCC.

PMID- 30282069
TI  - Large Cytoplasmic Vacuoles within Notochordal Nucleus Pulposus Cells: A Possible
      Regulator of Intracellular Pressure That Shapes the Cytoskeleton and Controls
      Proliferation.
AB  - Degeneration of the intervertebral disc, which is closely associated with the
      loss of vacuolated notochordal nucleus pulposus cells (NNPC), remains a major
      cause of lower-back pain and motor deficiency. Being the most defining
      characteristic of NNPC, large cytoplasmic vacuoles not only modulate the
      cytoskeleton and shape cell morphology but they also respond to the disc
      microenvironment and regulate the biological behavior of vacuolated cells as a
      potent reporter of the histocytological changes that occur at the beginning of
      disc aging and degeneration. Here we hypothesize a model in which large
      cytoplasmic vacuoles primarily function to maintain a reasonable intracellular
      pressure (Pv) that facilitates NNPC in resisting the extracellular mechanical
      loading (Pe), part of which is absorbed by the extracellular matrix (Pm), forming
      the equation Pe = Pm + Pv. By mimicking a situation of contact-induced growth
      inhibition, the crowded cytoplasmic vacuoles slow down the proliferation of NNPC
      and restrain the generation of nonvacuolated chondrocytic nucleus pulposus cells
      (CNPC), whereas increased mechanical loading (?Pe) alters cytoskeletons and
      breaches cytoplasmic vacuoles, which in turn weakens the vacuoles-mediated
      proliferation check, increases the generation of CNPC that accumulates
      fibrocartilaginous matrix, and rebalances the increased loading with elevated Pm
      (?Pm) and lowered Pv (?Pv), equating to ?Pe = ?Pm + ?Pv. By depicting the
      biological function and the disappearance of the cytoplasmic vacuoles, our model
      highlights a mechanical exhaustion of the notochordal cell resources, which might
      help to elucidate the histocytological changes that initiate disc aging and
      degeneration.

PMID- 30282068
TI  - H19 Functions as a Competing Endogenous RNA to Regulate EMT by Sponging miR-130a
      3p in Glioma.
AB  - BACKGROUND/AIMS: Glioma is one of the most devasting tumors and confers dismal
      prognosis. Long noncoding RNAs(lncRNAs) have emerged as important regulators in
      various tumors including glioma. A classic lncRNA-H19, which is found to be
      highly expressed in human glioma tissues and cell lines, and is associated with
      tumor progression thus predicating clinical outcomes in glioma patients. However,
      the overall biological functions and their mechanism of H19 in glioma are not
      fully understood. METHODS: Firstly, we analyzed H19 alterations in different
      grades of glioma tissues through an analysis of 5 sequencing datasets and qRT-PCR
      was performed to confirm the results. Next, we evaluated the effect of H19 on
      glioma cells migration, invasion and EMT process. Luciferase assays and RIP
      assays were employed to figure out the correlation of H19 and SOX4. RESULTS: H19
      was overexpressed in glioma tissues. Down-regulation of H19 led to the inhibition
      of migration, invasion and EMT process with a reduction in N-cadherin and
      Vimentin. H19 and SOX4 are both direct target of miR-130a-3p. H19 could compete
      with SOX4 via sponging miR-130a-3p. CONCLUSION: Taken together, these results
      provide a possible function of H19 as an oncogene in glioma tissues and provide a
      potential new therapeutic strategy for human glioma.

PMID- 30282070
TI  - Promoter Methylation of Ezrin and its Impact on the Incidence and Prognosis of
      Cervical Cancer.
AB  - BACKGROUND/AIMS: Aberrant localization and over-expression of Ezrin have been
      reported to be implicated in cervical cancer (CC). Aberrant promoter methylation
      of some gene families may serve as potential diagnostic biomarkers for CC. In
      this study, we explored the correlation of promoter methylation of the Ezrin gene
      with the incidence and prognosis of CC. METHODS: Cervical tissues from a total of
      483 patients with CC were collected from the China-Japan Union Hospital of Jilin
      University. Samples were assigned into four groups accordingly to pathological
      diagnosis, namely the control group, the cervical intraepithelial neoplasia (CIN)
      I group, the CIN II-III group and the CC group. Reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA
      expression of Ezrin. Methylation-specific polymerase chain reaction (MSP) was
      used to detect the promoter methylation of the Ezrin gene. The Kaplan-Meier
      product-limit method and the log-rank analysis were used for survival analysis,
      the Cox regression analysis for the prognostic factors for CC, and the logistic
      regression analysis for the risk factors for the occurrence of CC. RESULTS: The
      methylation rate of the Ezrin gene was correspondingly increased from the
      control, the CIN I, the CIN II-III to the CC groups. Over-expressed mRNA of Ezrin
      was determined in CC tissues. The mRNA expression of Ezrin was correlated with
      tumor size, lymphatic metastasis, pathological grade and clinical stage (FIGO).
      The risk factors for the occurrence of CC were the number of abortions and the
      promoter methylation of the Ezrin gene. Poor prognosis of CC correlated to
      lymphatic metastasis, higher pathological grade, higher FIGO stage and positive
      Ezrin promoter methylation. CONCLUSION: These findings indicate that promoter
      methylation of the Ezrin gene may play a crucial role in carcinogenesis,
      progression and prognosis of CC.

PMID- 30282071
TI  - Upregulation of P21-Activated Kinase 1 (PAK1)/CREB Axis in Squamous Non-Small
      Cell Lung Carcinoma.
AB  - BACKGROUND/AIMS: p21-activated Ser/Thr kinase 1 (PAK1) is essential for the
      genesis and development of many cancers. The purpose of this study was to
      investigate the role of the PAK1-cyclic AMP response element-binding (CREB) axis
      in non-small cell lung cancer (NSCLC) tumorigenesis and its related mechanisms.
      METHODS: Western blot assay and immunohistochemical staining were employed to
      investigate the PAK1 and CREB expression in the tissue microarray of human
      squamous NSCLC. Co-immunoprecipitation and immunofluorescence confocal assays
      were performed to determine the link between PAK1 and CREB. NSCLC xenograft
      models were used to study oncogenic function of PAK1 in vivo. RESULTS: We
      observed that PAK1 and CREB expression levels were significantly elevated in
      human squamous NSCLC-tissue specimens, compared with those in adjacent normal
      bronchial or bronchiolar epithelial-tissue specimens, as well as their
      phosphorylated forms, based on western blotting. We showed in vitro that PAK1
      knockdown by small-interfering RNA (siRNA) blocked CREB phosphorylation, whereas
      plasmid-based PAK1 overexpression resulted in CREB phosphorylation at Ser133,
      based on western blotting. In addition, PAK1 interacted with CREB in co
      immunoprecipitation assays. Additionally, our in vitro findings detected by flow
      cytometry revealed that PAK1 silencing attenuated cell cycle progression,
      inducing apoptosis. Inhibition of PAK1 expression reduced tumor sizes and masses
      by modulating CREB expression and activation in xenograft models. CONCLUSION:
      These results suggest a novel mechanism whereby the PAK1-CREB axis drives
      carcinogenesis of squamous-cell carcinomas, and have important implications in
      the development of targeted therapeutics for squamous-cell lung cancer.

PMID- 30282075
TI  - OK-432 Treatment of Early Fetal Chylothorax: Pregnancy Outcome and Long-Term
      Follow-Up of 14 Cases.
AB  - BACKGROUND: The treatment options for fetal chylothorax include thoracocentesis,
      thoracoamniotic shunting, and pleurodesis using OK-432. Knowledge on the long
      term outcomes after treatment with OK-432 is limited. OBJECTIVE: The aim of this
      study was to assess the long-term outcomes of children treated in utero with OK
      432. METHODS: We performed follow-up on pregnancies and children treated in utero
      with OK-432 between 2003 and 2009 at Copenhagen University Hospital
      Rigshospitalet for pleural effusions at gestational age (GA) 16+0-21+6 weeks.
      Anamnestic information, physical examination, pulmonary function test,
      neuropediatric examination, and intelligence testing using the Wechsler
      Intelligence Scale were used for evaluation. RESULTS: Fourteen cases, all
      chylothorax, were treated with OK-432. None had preterm premature rupture of
      membranes (PPROM), and the median GA at delivery was 38+5 (24+4-41+5) weeks.
      Twelve children were eligible for follow-up. The median age at follow-up was 11.4
      (7.8-13.8) years. Pulmonary function was normal in all children and the mean full
      scale IQ did not differ from that of normal children. Four children had a
      diagnosed medical condition, attention deficit disorder, or genetic syndrome. The
      remaining children had normal follow-up. CONCLUSION: Children treated with OK-432
      have comparable survival rates and long-term neurodevelopmental outcomes to those
      treated with thoracoamniotic shunts. There seems to be a lower risk of procedure
      related PPROM.

PMID- 30282072
TI  - MicroRNA-34a Attenuates Paclitaxel Resistance in Prostate Cancer Cells via Direct
      Suppression of JAG1/Notch1 Axis.
AB  - BACKGROUND/AIMS: Treatment options for metastatic castrate-resistant prostate
      cancer (mCRPC) are limited and typically centered on paclitaxel-based
      chemotherapy. In this study, we aimed to evaluate whether miR-34a attenuates
      chemoresistance to paclitaxel by regulating target genes associated with drug
      resistance. METHODS: We used data from The Cancer Genome Atlas to compare miR-34a
      expression levels in prostate cancer (PC) tissues with normal prostate tissues.
      The effects of miR-34a inhibition and overexpression on PC proliferation were
      evaluated in vitro via Cell Counting Kit-8 (CCK-8) proliferation, colony
      formation, apoptosis, and cell-cycle assays. A luciferase reporter assay was
      employed to identify the interactions between miR-34a and specific target genes.
      To determine the effects of up-regulation of miR-34a on tumor growth and chemo
      resistance in vivo, we injected PC cells overexpressing miR-34a into nude mice
      subcutaneously and evaluated the rate of tumor growth during paclitaxel
      treatment. We examined changes in the expression levels of miR-34a target genes
      JAG1 and Notch1 and their downstream genes via miR-34a transfection by
      quantitative reverse transcription PCR (qRT-PCR) and western blot assay. RESULTS:
      miR-34a served as an independent predictor of reduced patient survival. MiR-34a
      was down-regulated in PC-3PR cells compared with PC-3 cells. The CCK-8 assay
      showed that miR-34a overexpression resulted in increased sensitivity to
      paclitaxel while miR-34a down-regulation resulted in chemoresistance to
      paclitaxel in vitro. A study of gain and loss in a series of functional assays
      revealed that PC cells expressing miR-34a were chemosensitive. Furthermore, the
      overexpression of miR-34a increased the sensitivity of PC-3PR cells to
      chemotherapy in vivo. The luciferase reporter assay confirmed that JAG1 and
      Notch1 were directly targeted by miR-34a. Interestingly, western blot analysis
      and qRT-PCR confirmed that miR-34a inhibited the Notch1 signaling pathway. We
      found that miR-34a increased the chemosensitivity of PC-3PR cells by directly
      repressing the TCF1/ LEF1 axis. CONCLUSION: Our results showed that miR-34a is
      involved in the development of chemosensitivity to paclitaxel. By regulating the
      JAG1/Notch1 axis, miR-34a or its target genes JAG1 or Notch1 might serve as
      potential predictive biomarkers of response to paclitaxel-based chemotherapy
      and/or therapeutic targets that will help to overcome chemoresistance at the
      mCRPC stage.

PMID- 30282074
TI  - The Munich-Transarterial Chemoembolisation Score Holds Superior Prognostic
      Capacities Compared to TACE-Tailored Modifications of 9 Established Staging
      Systems for Hepatocellular Carcinoma.
AB  - BACKGROUND/AIMS: The recently proposed Munich-transarterial chemoembolisation
      score (M-TACE) was tailored to suit hepatocellular Carcinoma (HCC) patients
      evaluated for TACE. M-TACE outperformed the established HCC-staging-systems and
      successfully passed external validation. Modifications of staging-systems through
      the rearrangement of stages or by adding prognostic factors are methods of
      improving prognostic power. M-TACEs performance compared to scores modified this
      way should be tested. METHODS: Seven well-known HCC staging-systems (including
      Cancer of the Liver Italian Program-score [CLIP] and Barcelona Clinic liver
      cancer [BCLC]) and 2 TACE-specific scores (Selection for Transarterial
      Chemoembolisation Treatment [STATE] and Hepatoma Arterial embolisation Prognostic
      [HAP]) were rearranged in a cohort of 186 TACE-patients through score-point
      analysis and subsequent linking of non-significant adjacent score-points.
      Additionally, a new score was constructed by combining the top established
      staging-system in TACE patients (CLIP-TACE) and the prognostic parameter with the
      highest hazard ratio for death in the TACE-cohort [C-reactive protein (CRP)].
      Additionally, the TACE-tailored-scores were applied to an external TACE-cohort (n
      = 71). -Results: Rearrangement resulted in optimal stratification and
      monotonicity. CLIP-TACE demonstrated the best prognostic capability of all
      rearranged scores (c-index 0.668, AIC 1294) and the addition of CRP yielded
      further prognostic improvement (c-index 0.680, AIC 1289). However, superiority
      over M-TACE could not be achieved by any of the new scores in the internal and
      external cohort. CONCLUSION: M-TACE outperforms TACE-tailored modifications of
      all relevant HCC-staging-systems. Prospective validation of M-TACE to promote its
      role as the preferred staging-system for TACE-patients is therefore justified.

PMID- 30282076
TI  - Gender, Age, and Concomitant Diseases of Colorectal Diverticulum in China: A
      Study of 7,964 Cases.
AB  - AIM: To analyze the epidemiological features of colorectal diverticulum (CRD) in
      China. METHODS: We retrospectively analyzed CRD patients in 8 tertiary hospitals
      located in 5 regions of China from 2000 to 2016. The detection rates, number and
      distribution, demographic information, concomitant disorders, and their
      associations were investigated. RESULTS: Of 3,446,118 cases, 7,964 (2.3%) were
      CRD with a mean age of 56 years (11-92 years). The detection rate increased
      yearly and with increasing age. Males had a higher detection rate than females
      (3.0 vs. 1.47%, p < 0.01) and 1.8-times higher increase rate. The detection rate
      increased with age; however, females of > 60 years had a 2.8-times increasing
      rate than males. CRD occurred most frequently in the right-side colon, followed
      by rectum. Multiple diverticula were common in males and increased with age, with
      a 3-times higher increase rate than single lesion. Single-segment CRD occurred
      more frequently in males than in females (80.1 vs. 76.4%, p < 0.01). Concurred
      colon polyps were seen in 51.05% cases. CONCLUSION: CRD detection rates increased
      annually and with age, particularly in senior females in China. Multiple
      diverticula were common in males and increased with age. CRD was predominant in
      the right-side colon. Polyps are the most common comorbidity associated with CRD.

PMID- 30282077
TI  - Effects of Sodium Hyaluronate on Symptoms and Quality of Life in Women Affected
      by Pregnancy Rhinitis: A Pilot Study.
AB  - AIMS: To investigate sodium hyaluronate (SH) efficacy in the treatment of
      pregnancy rhinitis. METHODS: A single-center, prospective, open-label, 2 parallel
      group study was carried out. Pregnant women affected by pregnancy rhinitis were
      randomly assigned to 1 of 2 groups: Group A was treated with SH, while Group B
      did not receive any treatment. Pregnancy rhinitis symptoms and quality of life
      (QOL) during pregnancy were investigated by administering a questionnaire and
      carrying out an otorhinolaryngoiatric visit. RESULTS: A significant reduction in
      the intensity of headache, snoring and insomnia in the Group A compared to the
      Group B were demonstrated. In the Group A, a significant lower presence of amount
      of secretions (Group A 0.88, 95% CI 0.57-1.18 vs. Group B 2.00, 95% CI 1.69-2.31,
      p < 0.001), turbinate hypertrophy (Group A 1.70, 95% CI 1.46-1.94 vs. Group B
      2.53, 95% CI 2.29-2.77, p < 0.001), and mucosal congestion/hyperemia (Group A
      1.41, 95% CI 1.14-1.68 vs. Group B 2.26, 95% CI 1.99-2.53, p < 0.001) was
      observed. No adverse events were reported in patients treated with SH.
      CONCLUSIONS: SH is a safe and effective therapeutic alternative for the treatment
      of pregnancy rhinitis symptoms, improving patients' QOL.

PMID- 30282073
TI  - Divergent Effects of Cyclophilin-D Inhibition on the Female Rat Heart: Acute
      Versus Chronic Post-Myocardial Infarction.
AB  - BACKGROUND/AIMS: The mitochondrial permeability transition pore opening plays a
      critical role in the pathogenesis of myocardial infarction. Inhibition of
      cyclophilin-D (CyP-D), a key regulator of the mitochondrial permeability
      transition pore, has been shown to exert cardioprotective effects against
      ischemia-reperfusion injury on various animal models, mostly in males. However,
      failure of recent clinical trials requires a detailed elucidation of the
      cardioprotective efficacy of CyP-D inhibition. The aim of this study was to
      examine whether cardioprotective effects of sanglifehrin A, a potent inhibitor of
      CyP-D, on post-infarcted hearts depends on reperfusion. METHODS: Acute or chronic
      myocardial infarction was induced by coronary artery ligation with/without
      subsequent reperfusion for 2 and 28 days in female Sprague-Dawley rats. Cardiac
      function was estimated by echocardiography. Oxygen consumption rates, ROS
      production, permeability transition pore opening, protein carbonylation and
      respiratory supercomplexes were analyzed in isolated cardiac mitochondria.
      RESULTS: Sanglifehrin A significantly improved cardiac function of reperfused
      hearts at 2 days but failed to protect after 28 days. No protection was observed
      in non-reperfused post-infarcted hearts. The respiratory control index of
      mitochondria was significantly reduced in reperfused infarcted hearts at 2-days
      with no effect at 28-days post-infarction on reperfused and non-reperfused
      hearts. Likewise, only a minor increase in reactive oxygen species production was
      observed at 2-days in non-reperfused post-infarcted hearts. CONCLUSION: This
      study demonstrates that CyP-D inhibition exerts cardioprotective effects in
      reperfused but not in non-reperfused infarcted hearts of female rats, and the
      effects are observed only during acute post-infarction injury.

PMID- 30282078
TI  - Endoscopic Retrograde Cholangio-Pancreatography-Obtained Bile Culture Can Guide
      Antibiotic Therapy in Acute Cholangitis.
AB  - BACKGROUND: Only a small proportion of patients with biliary tree infection grow
      microorganisms in blood cultures. Antibiotics chosen or tailored based on
      organisms identified on blood cultures have a potential for under-treatment and
      unfavorable outcomes, including recurrent infection and early stent occlusion. In
      our current practice, we collect bile for culture if an Endoscopic Retrograde
      Cholangio-Pancreatography (ERCP) is performed in patients with suspected
      cholangitis. In this study, we compare the microbial yield of blood cultures and
      ERCP-obtained bile cultures in patients with ascending cholangitis. METHODS: We
      reviewed medical records of all the patients treated for ascending cholangitis
      who had blood cultures and ERCP-obtained bile cultures at a tertiary care center
      between 2010 and 2016. Bile was collected for culture before injecting contrast,
      via a catheter after discarding the initial 3 mL. RESULTS: Ninety-three patients
      were included with mean age of 71 (+/-15) years. Out of 93 patients, 11 (12%) had
      prior sphincterotomy, 29 (31%) had an indwelling biliary stent, and malignant
      obstruction was the most common etiology (34%). ERCP-obtained bile cultures were
      positive in 90 out of 93 (97%) patients with monomicrobial growth in 34 out of 93
      (39%) patients. Mixed intestinal flora was noted in 3 patients. Blood cultures
      were positive in only 30 out of 93 patients (32%) and 24 out of 93 (26%) patients
      had monomicrobial growth. Totally 26 out of 30 patients (87%) grew the same
      organism as the bile culture, 3 grew an organism different from bile cultures,
      and one had no growth in the bile culture. On multivariable analysis, the
      presence of an indwelling biliary stent was the lone factor associated with
      polymicrobial growth, 83 vs. 52%, p = 0.007. CONCLUSION: ERCP-obtained bile
      cultures are a reliable and feasible mechanism to evaluate patients with
      suspected biliary tree infection. This technique has a significantly higher yield
      when compared to blood culture. Selection and tailoring of antibiotics based on
      bile culture in the management of ascending cholangitis are advised.

PMID- 30282080
TI  - Precision Medicine Made with Silicone.

PMID- 30282079
TI  - Risky Alcohol Use: The Impact on Health Service Use.
AB  - OBJECTIVE: To examine health services use on the basis of alcohol consumption.
      MATERIAL AND METHODS: A cross-sectional study was carried out on patients
      visiting the Primary Health Care (PHC) settings in Catalonia during 2011 and
      2012; these patients had a history of alcohol consumption. Information about
      outpatient visits in the PHC setting, hospitalizations, specialists' visits and
      emergency room visits for the year 2013 was obtained from 2 databases (the
      Information System for the Development of Research in PHC and the Catalan Health
      Surveillance System). Risky drinkers were defined as those who consumed more than
      280 g per week for men or more than 170 g per week for women, or any amount of
      alcohol while being involved in a high risk work activity, or taking medication
      that significantly interferes with alcohol or when being pregnant. Binge drinkers
      (> 60 g in men or > 50 g in women in a short amount of time more than once a
      month) were also considered risky drinkers. RESULTS: A total of 606,948 patients
      reported consuming alcohol (of which 10.5% were risky drinkers). Risky drinkers
      were more likely to be admitted to hospitals or emergency departments (range of
      ORs 1.08-1.18) compared to light drinkers. Male risky drinkers used fewer PHC
      services than male light drinkers (OR 0.89, 95% CI 0.87-0.92). In general, risky
      alcohol users used services more and had longer hospital stays. When stratifying
      by socioeconomic level of the residential area, we found that risky drinking
      failed significance, while current or past cigarette smoking was associated with
      higher healthcare use. CONCLUSIONS: Risky drinkers use more expensive services,
      such as hospitals and emergency rooms, but not PHC services, which may suggest
      that prevention strategies and alcohol interventions should also be implemented
      in those settings.

PMID- 30282081
TI  - Zone Formation of Lymphocyte Infiltration at Invasive Front as a Biomarker of
      Prognosis in Endometrial Carcinomas.
AB  - OBJECTIVE: The clinical significance of lymphocyte infiltration (LI) at the
      invasive front in endometrial carcinomas (EC) has not been determined. The aim of
      the current study was to evaluate the association between zone formation of LI at
      the invasive front of the tumor margin and prognoses of the patients with EC.
      METHODS: All available pathological slides of the enrolled cases were reviewed,
      and the degree of LI at the invasive front was categorized into 2 groups: strong
      LI and weak LI. Clinical significance of LI was evaluated retrospectively.
      RESULTS: A total of 333 cases with EC were enrolled in the study: 225 cases with
      weak LI and 108 cases with strong LI. Weak LI was more frequently observed in the
      patients with grade1/2 endometrioid EC. Multivariate analyses for progression
      free survival (PFS) and overall survival (OS) revealed that weak LI was
      identified as an independent worse prognostic factor for OS (p = 0.004) in
      addition to PFS (p = 0.022). CONCLUSION: Weak LI at the invasive front of the
      tumor margin was associated with worse prognoses in EC. Although further studies
      are needed, it is suggested that LI could be a biomarker of prognoses in EC.

PMID- 30282082
TI  - Neuroendocrine Breast Carcinomas Share Prognostic Factors with
      Gastroenteropancreatic Neuroendocrine Tumors: A Putative Prognostic Role of
      Menin, p27, and SSTR-2A.
AB  - OBJECTIVES: Due to the rarity of breast carcinomas with neuroendocrine features
      (NEBC), the knowledge on their biology is very limited but the identification of
      their biology and prognostic factors is essential to evaluate both pathogenesis
      and possible targeted treatment options. We assessed the expression of the well
      characterized prognostic factors of gastroenteropancreatic neuroendocrine tumors
      (GEP-NET) in NEBC. METHODS: We assessed the immunohistochemical expression of
      neuron-specific enolase (NSE), thymidylate synthase (TS), p27, CD56, menin, and
      somatostatin receptor type 2A (SSTR-2A) in a series of 36 NEBC and 45 invasive
      ductal carcinomas (IDC). RESULTS: Nuclear and cytoplasmic TS, nuclear and
      cytoplasmic NSE, and nuclear p27 had significant overexpression in NEBC compared
      with IDC (for all, p < 0.01). In NEBC, cytoplasmic SSTR-2A expression was
      associated with excellent distant disease-free survival (p = 0.013), cytoplasmic
      menin expression with poorer relapse-free survival (p = 0.022), and nuclear p27
      with longer breast cancer-specific survival (p = 0.022). CONCLUSIONS: There is a
      striking similarity in GEP-NET and NEBC regarding prognostic factors. GEP-NET and
      NEBC also appear to show similar expression patterns of the studied markers,
      while there are notable differences compared to IDC. Due to the wide expression
      of SSTR-2A, the treatment option with somatostatin analogs in NEBC should be
      evaluated.

PMID- 30282083
TI  - Unmet Needs in Functional and Nonfunctional pancreatic neuroendocrine
      neoplasms(PanNENs).
AB  - Recently, European Neuroendocrine Tumor Society (ENETS )held working sessions
      composed of members of the advisory board and other Neuroendocrine neoplasms
      (NEN) experts to attempt to identify unmet needs in NENs in different locations
      or with advanced/poorly differentiated NENs. This section briefly summarizes the
      main proposed areas of unmet needs in patients with functional and non-functional
      pancreatic neuroendocrine neoplasms (PanNENs).

PMID- 30282084
TI  - Fits of Implant Zirconia Custom Abutments and Frameworks: A Systematic Review and
      Meta-Analyses.
AB  - PURPOSE: The aim of this systematic review and meta-analyses was to evaluate fits
      of zirconia custom abutments and frameworks on implants and to identify the
      factors that influence their fits. MATERIALS AND METHODS: An electronic search
      was conducted through PubMed (MEDLINE), Google Scholar, and Cochrane Central
      Registrar of Controlled Trials. The search was completed in August 2017. Series
      of meta-analyses were conducted to compare fits of zirconia custom abutments and
      frameworks on implants with metal abutments and frameworks. The interest
      variables were the interface gap and the rotational misfit of abutments and the
      vertical fit of frameworks. RESULTS: Initially, a total of 672 articles were
      identified from the electronic search. After applying the inclusion criteria, 17
      suitable articles were selected, including 9 studies on the fit of zirconia
      custom abutments and 8 studies on the fit of zirconia frameworks. There is a
      tendency for zirconia abutments to exhibit greater interface gaps and rotational
      misfits than metal abutments. Abutments produced by manual-aided designs/manual
      aided manufacturing (MAD/MAM) exhibited inferior fits compared with those
      produced by computer-aided design/computer-aided manufacturing (CAD/CAM).
      Proprietary abutments had superior fits compared with non-proprietary abutments.
      Milled zirconia frameworks had insignificantly inferior fits compared with milled
      metal frameworks. CONCLUSION: Within the limitations of this study, custom
      zirconia abutments and non-proprietary abutments appeared to exhibit slightly
      inferior fits compared with metal abutments or abutments produced by the same
      implant company. However, the clinical significance of this difference is yet to
      be determined. The fit of milled zirconia frameworks is generally comparable to
      milled metal frameworks.

PMID- 30282085
TI  - Imaging Aspects Of The Mandibular Incisive Canal: A PROSPERO-Registered
      Systematic Review And Meta-Analysis Of Cone Beam Computed Tomography Studies.
AB  - PURPOSE: This study aimed to perform a systematic review and meta-analysis of the
      literature on the mandibular incisive canal (MIC) studies using cone beam
      computed tomography (CBCT). MATERIALS AND METHODS: A PROSPERO-registered
      systematic review (#42017056619) was conducted following the PRISMA statements to
      summarize current knowledge on the CBCT aspects of the MIC. A search was
      performed in PubMed's Medline and Scopus databases, without date or language
      restrictions, using the algorithm {[(Interforaminal region) OR (mandibular
      incisive channel) OR (mandibular incisive nerve) OR (mental mandible) OR
      (anterior mandible) (cone beam computed tomography). Also, the references were
      crosschecked. The Meta-Analysis of Statistics Assessment and Review Instrument
      and meta-analysis was used to evaluate the selected studies. RESULTS: A total of
      410 articles were found, and 25 studies were selected after a two-step selection
      process. The CBCT systems differed regarding field of view (FOV) (large, n = 3;
      medium, n = 2; small, n = 4; not informed, n = 16) and voxel size (0.15 to 0.4
      mm). Geographically, the studies were distributed across four continents (South
      America, North America, Asia, and Europe), and there was a statistical
      significance of studies from the American and Asian continents (P < .0001). From
      3,421 CBCT exams, the number of female patients was slightly higher than male,
      and the mean age ranged from 29.8 to 59.1 years. The overall mean prevalence of
      MIC was 89.6% +/- 15.08%, and bilateral occurrence was statistically significant
      (P < .0001). The studies using a voxel size lower than 0.3 mm showed the highest
      mean prevalence (93.88%) in comparison with voxel size described as >= 0.3 mm
      (89.33%). Diameter (0.45 to 4.12 mm) and length (6.6 to 40.3 mm) showed great
      variability among the included studies. CONCLUSION: In summary, the results of
      this systematic review evidenced a high worldwide prevalence of MIC. There was no
      prevalence of MIC in relation to sex, and its presence was mainly related to
      adults between the fourth and sixth decades of life. In addition, great
      heterogeneity of methodologies was observed.

PMID- 30282086
TI  - Hard and soft tissue cell behavior on PEEK, Zirconia, and Titanium implant
      materials.
AB  - PURPOSE: The aim of this study was to characterize and compare the behavior of
      human osteoblasts and human gingival fibroblasts in contact with
      polyetheretherketone (PEEK), zirconia, and titanium implant surface materials.
      MATERIALS AND METHODS: PEEK, yttria-stabilized zirconia (YTZP), and titanium
      discs were produced under appropriate and similar conditions to achieve
      controlled surface features. Human osteoblasts and human gingival fibroblasts
      were cultured on discs for 14 days. Cell viability and proliferation were
      evaluated using a resazurin-based method. Morphology and cellular adhesion were
      observed using field emission gun-scanning electron microscopy (FEG-SEM).
      Alkaline phosphatase (ALP) activity and bone cell mineralization were evaluated
      on osteoblasts. Confocal laser scanning microscopy (CLSM) images of fluorescent
      stained fibroblasts were obtained at 7 and 14 days of the culture. Results were
      presented as mean and standard deviation (SD). Group comparisons were tested
      using analysis of variance (ANOVA) (Tukey's post hoc) with appropriate
      statistical software, and significance was set at P < .05. RESULTS: Cell
      viability and proliferation were higher in PEEK and YTZP groups compared with
      titanium on osteoblast cells (P < .05, all time points) and on fibroblasts (P <
      .05, 7 and 14 days). All groups showed an increase in ALP activity over time,
      which was not significant. Mineralization patterns demonstrated an increase in
      mineral content over time, which was more apparent in the YTZP group. Cell
      spreading was more evident on PEEK and YTZP specimens. CONCLUSION: The results
      suggest increased adhesion, viability, and proliferation of osteoblasts and
      gingival fibroblasts on zirconia and PEEK surfaces compared with titanium. These
      results are correlated with the increased wettability of these materials.

PMID- 30282087
TI  - An Evaluation of the Relationship Between Peri-implant Soft Tissue Biotype and
      the Severity of Peri-implantitis: A Cross-Sectional Study.
AB  - PURPOSE: This cross-sectional study aimed to analyze the relation between peri
      implant soft tissue biotype (STB) and different levels of peri-implantitis
      severity, and to identify the possible risk indicators that affect the severity
      of peri-implantitis with regard to STB around dental implants. MATERIALS AND
      METHODS: Eighty-seven patients with 229 implants were diagnosed with peri
      implantitis and recruited to the study. Clinical and radiographic parameters
      including Plaque Index (PI), probing depth (PD), bleeding on probing (BOP),
      gingival/mucosal recession (GR/MR), clinical attachment level (CAL), and marginal
      bone loss (BL) were analyzed. The periodontal status was assessed, and the levels
      of peri-implantitis severity were defined. These parameters were compared among
      the peri-implant STB groups (thick and thin biotype). To evaluate the effect of
      possible risk indicators on the levels of severity of peri-implantitis,
      univariate and multivariate logistic regression analyses were conducted for thick
      and thin biotype groups. RESULTS: The mean values of BOP, MR, CAL, and marginal
      BL were significantly lower for the thick group compared with the thin group (P <
      .05). For PI and PD values, no significant differences were found between the
      groups (P > .05). Moreover, multivariate analysis revealed statistically
      significant associations between peri-implantitis severity and the risk
      indicators maintenance therapy compliance and current periodontitis for the thin
      group (P < .05). CONCLUSION: The thin biotype could be more prone to increase in
      the severity of peri-implantitis. Maintenance therapy compliance and current
      periodontitis could be important risk indicators that affect the progression of
      the severity of peri-implantitis for implants where keratinized mucosa is thin or
      absent.

PMID- 30282088
TI  - Radiographic Assessment Of Crestal Bone Loss In Tissue-Level Implants Restored By
      Platform Matching Compared With Bone-Level Implants Restored By Platform
      Switching: A Randomized, Controlled, Split-Mouth Trial With 3-Year Follow-Up.
AB  - PURPOSE: This randomized, controlled, split-mouth trial with 3-year follow-up was
      carried out to compare radiologic changes of crestal bone level (CBL) between
      splinted tissue-level implants restored by platform matching and bone-level
      implants restored by platform switching. MATERIALS AND METHODS: Periapical
      radiographs were taken to evaluate the peri-implant crestal bone changes at
      baseline (implant restoration), at 1 year, and at 3 years after the definitive
      restoration. RESULTS: Thirty-five patients requiring a partial fixed dental
      prosthesis supported by two implants had their sites randomized according to
      receiving both implant types. Fifty tissue-level implants restored by platform
      matching, as control implants, and 50 bone-level implants restored by platform
      switching, as test implants, were placed. Crestal bone changes in the control
      group were: baseline to 3 years, 0.18 +/- 0.46 mm (P = .043). In the test group,
      crestal bone changes were: baseline to 3 years, 0.14 +/- 0.35 mm (P = .514). The
      mean differences between groups were: baseline to 1 year, 0.07 +/- 0.23 mm (95%
      CI: -0.034, 0.185); 1 to 3 years, 0.01 +/- 0.01 mm (95% CI: -0.055, 0.074);
      baseline to 3 years, 0.04 +/- 0.11 mm (95% CI: -0.080, 0.150). No statistically
      significant differences in CBL at baseline to 1 year (P = .269), 1 year to 3
      years (P = .811), and baseline to 3 years (P = .513) were observed. CONCLUSION:
      In this trial, CBL changes in the tissue level control group were statistically
      significant only between baseline and 3-year follow-up. Meanwhile, CBL changes in
      the bone-level test group were not statistically significant in the different
      times studied. No statistically significant difference in CBL between two implant
      types was observed.

PMID- 30282089
TI  - Resonance Frequency Analysis: Agreement and Correlation of Implant Stability
      Quotients Between Three Commercially Available Instruments.
AB  - PURPOSE: The purpose of this study was to analyze the implant stability quotient
      (ISQ) values recorded by three commercially available resonance frequency
      analysis (RFA) instruments from a large cohort of implants in order to determine
      their accuracy and agreement with one another both for static measurements of ISQ
      at a given time and for change in ISQ over time. MATERIALS AND METHODS: A cohort
      of n = 210 implants had their primary stability, secondary stability, or both
      evaluated in both the mesiodistal (MD) and buccolingual (BL) directions by means
      of ISQ using three different RFA instruments: Osstell Mentor (OM), Osstell Idx
      (OI), and the Penguin (PG). ISQ values were recorded both at the time of implant
      placement and at 3 months postinsertion prior to definitive restoration. All
      values were tabulated for a blinded statistical analysis using Bland Altman plots
      to determine if the outcome values were in agreement both for primary and
      secondary stability. In addition, a subgroup was evaluated to determine if change
      in ISQ was also in agreement. An intraclass correlation (ICC) was used to measure
      the reliability of the measurements for each instrument. RESULTS: Bland Altman
      plots confirmed that there was a high agreement for MD values between OM and OI,
      with 72.7% of readings being within one ISQ unit and 94.7% within four units.
      Comparing PG to OM, the respective values at one and four units were 15.3% and
      82.3%, and comparing PG to OI, the respective values were 16.3% and 85.2%. In
      general, there was a greater uncertainty in the BL values having wider
      variability and demonstrating less agreement between instruments, with the
      percentage of readings falling within four units reducing to 85.9% (OM vs OI),
      72.3% (PG vs OM), and 74.3% (PG vs OI). 92.3% of values were in agreement to
      within four units between instruments OM and OI for change in ISQ over time in
      the MD direction and 73% in the BP direction. The respective percentage changes
      of values in agreement within four units for PG vs OM were 76.9% and 60.3% and
      for PG vs OI were 80% and 53.8%. Paired t test from mixed effects revealed that
      there was a significant difference for mean MD values between PG vs OM; P = .015
      with on average 0.823 units higher was recorded for PG. Similarly for PG vs OI, P
      = .008 with on average 0.871 units higher was recorded for PG. For mean BL values
      between PG vs OI, P = .000 with on average 1.161 units higher was recorded for
      PG, and finally, for OM vs OI, P = .005 with on average 0.597 units higher was
      recorded for OM. However, the maximum upper and lower bound estimated bias
      between any two instruments was only 1.86 units and 0.46 units both for PG vs OI
      in the BP direction, and it is doubtful that this is of clinical relevance even
      if statistically significant. ICC revealed that for static MD measurements, there
      was an 85% reliability between all three instruments. The highest reliability was
      between OM and OI instruments (97%), and the lowest reliability was when
      comparing results between PG and OM instruments (79%). For BL measurements, these
      reliability values were 66%, 71%, and 69%, respectively. When considering ICC for
      changes in ISQ values over time in the MD direction, there was a 70% reliability
      between all three instruments. The highest reliability was between OM vs OI
      instruments (94%), and the lowest reliability was when comparing results between
      PG vs OM instruments (58%). For BL measurements, these reliability values were
      58%, 91%, and 46%, respectively. CONCLUSION: Differences exist between all three
      instruments to a greater or lesser extent, with the most notable differences
      between the Penguin and the two instruments from Osstell, which showed both good
      agreement and reliability to each other. While the differences apparent in
      evaluating ISQ with the Penguin were statistically significant, they were less
      than 1.86 units at the upper bound limit, and it is doubtful that this is of
      clinical significance. Of greater clinical importance is the much-increased
      variability and reduced reliability for BL values as to render these less
      clinically sound compared with MD values when trying to assess primary stability.

PMID- 30282091
TI  - Anatomical and Biologic Considerations of Autogenous Bone Blocks Harvested from
      the Ramus Region.
AB  - A common site to harvest autogenous bone is the posterior mandible (ramus). Bone
      from this area may be cortical or cancellous in nature with different levels of
      osteogenic potential. Management of deficient alveolar ridges must be based upon
      anatomical and biologic characteristics of the donor bone from the ramus. This
      technical report provides all aspects of the presurgical planning, topographic
      features of autogenous ramus blocks, and loading concepts according to the
      biologic characteristics and resorption properties of these blocks. Long-term
      data from clinical cases are presented improving the clinical outcomes with high
      predictability.

PMID- 30282090
TI  - Clinical Outcome Of Dental Implant Therapy In Association With Le Fort I
      Osteotomy Preprosthetic Surgery: A Systematic Review.
AB  - PURPOSE: The purpose of this systematic review was to evaluate the outcome of
      dental implant treatment in fully edentulous patients who underwent Le Fort I
      osteotomy as a preprosthetic surgical technique. MATERIALS AND METHODS: A search
      was conducted of the PubMed (MEDLINE), EMBASE, Scopus, and Cochrane databases to
      identify records published from 1995 to 2017 dealing with Le Fort I osteotomy
      procedures for implant placement purposes. The primary outcomes of interest were
      the survival and success rates. The secondary outcomes consisted of the analysis
      of intra- and postsurgical complications and the surgical and prosthetic loading
      protocols. RESULTS: Overall, 20 articles were selected for data analysis. A total
      of 483 patients accounting for 3,596 implants were analyzed. The cumulative
      survival rate was 90.22% +/- 0.8% at 10 years (mean: 59.20 +/- 32.31 months). The
      cumulative success rate was 89.07% +/- 1.3% at 10 years (mean: 62.82 +/- 25
      months). Higher survival rates were found for implants with a rough surface (P <
      .001) and for implants loaded with a delayed protocol (P < .001). The fracture of
      the palatine bone during the downfracture procedure was the main intrasurgical
      drawback, while sinus pathology and graft resorption were commonly observed
      during the postoperative healing. Surgical and prosthetic loading protocols were
      heterogenous. CONCLUSION: Based on this review, Le Fort I osteotomy might be
      considered a viable technique to recreate favorable conditions for implant
      supported rehabilitations. Caution has to be taken when using machined implants,
      particularly in the case of a simultaneous approach.

PMID- 30282092
TI  - The implant surface and its role in affecting the dynamic processes of bone
      remodeling by means of distance osteogenesis: A comparative in vivo study.
AB  - PURPOSE: This study aimed to evaluate whether different surface modifications
      affect the dynamics of bone remodeling at the implant and the adjacent local
      bone. MATERIALS AND METHODS: Seventy-two dental implants with different surfaces
      (smooth and rough control [smCtrl; rCtrl], smooth and rough + O2-plasma spray
      [smPlas; rPlas], smooth and rough + nanocrystalline SiO2-hydroxyapatite coating
      [ncSiO2HA] + O2-plasma spray [smNB-C; rNB-C]; each n = 12) were bilaterally
      inserted into the femora of 36 New Zealand white rabbits. Intravital fluorochrome
      labeling was performed to visualize the dynamics of bone formation. The
      objectives were quantification of bone-to-implant contact (BIC [%]) at 2 and 4
      weeks and the dynamic bone formation (dbf [%]) at the implants' adjacent local
      bone within 1, 2, and 3 weeks. RESULTS: After 2 weeks, BIC was significantly
      higher for both smNB-C (BIC: 59% +/- 2% SEM) and rNB-C (BIC: 66% +/- 3% SEM)
      compared with controls (BIC: 42% +/- 1% SEM; P < .005). After 4 weeks, BIC for
      rNB-C (65% +/- 2%) was superior to all test groups (BIC: 39% +/- 2% SEM; P =
      .012). Regarding dbf (%), neither within 1 (P = .88), 2 (P = .48), nor after 3
      weeks (P = .36) did any differences occur among the groups, even in accordance to
      the implant level. CONCLUSION: Although distance osteogenesis seems crucial for
      the development of secondary stability and thus of osseointegration, it
      apparently does not get affected by a bioactive ncSiO2HA surface coating.
      Changing the surfaces' release kinetics and composition may increase distance
      osteogenesis.

PMID- 30282093
TI  - A simplified soft tissue management for peri-implant bone augmentation.
AB  - PURPOSE: This case series illustrates a simplified soft tissue management,
      namely, the subperiosteal peri-implant augmented layer (SPAL), to increase hard
      and soft tissue dimensions at the most coronal portion of an implant. MATERIALS
      AND METHODS: Twenty-seven implants in 16 patients presenting either a buccal bone
      dehiscence or a thin (< 1 mm) buccal cortical bone plate (BCBP) were
      consecutively treated. Briefly, a split-thickness flap (namely, the mucosal
      layer) was raised on the buccal aspect. Then, the periosteal layer was elevated
      from the bone crest. A full-thickness flap was elevated on the oral aspect. After
      implant site preparation, a xenograft was used to fill the space between the
      periosteal layer and the BCBP and/or exposed implant surface and, if present, to
      completely correct the bone dehiscence. The periosteal layer was sutured to the
      oral flap. The mucosal layer was coronally advanced and sutured to submerge both
      the graft and the implants. At 3 to 6 months, a re-entry procedure for implant
      exposure was performed. RESULTS: Healing was uneventful, with no signs of
      infection in all cases. A wound dehiscence was observed in three implants in two
      patients at 2 weeks postsurgery. Out of 15 implants showing an initial bone
      dehiscence, 12 implants (80%) showed a complete resolution, with a subperiosteal
      tissue thickness (SPTT) at the time of re-entry of 3.1 +/- 1.0 mm. Three implants
      presented a residual dehiscence of 1 mm (two implants) or 2 mm (one implant),
      with a SPTT of at least 2 mm. Out of 12 implants showing a thin BCBP at implant
      placement, 10 implants (90%) revealed a SPTT >= 2 at the time of re-entry. Two
      implants revealed a SPTT of 1 mm. CONCLUSION: The SPAL technique represents a
      valuable simplified surgical approach associated with a low rate of complications
      in the treatment of peri-implant bone dehiscence and in the horizontal
      augmentation of peri-implant tissue thickness.

PMID- 30282095
TI  - Exercise and Air-Travel-Induced Alterations in Blood Hemostasis.
AB  - Hemostasis is the ability of the body to control blood loss following vascular
      injury. The process is composed of a complex array of pathways made up of the
      coagulation and fibrinolytic systems that allow the fluid blood to clot after
      injury and then the subsequent breakdown of the clot, permitting repair of the
      injured tissue. Studies to date have shown exercise to be a stimulating factor in
      both the coagulation and fibrinolytic pathways. Additionally, air travel has been
      shown to be a risk factor for thrombosis. However, few studies have examined the
      combination of exercise and air travel on hemostasis, despite documented evidence
      of venous thrombotic episodes in the sports and endurance (marathon/triathlon)
      communities. This review summarizes and analyzes the literature with regard to
      (1) acute and chronic exercise, (2) air travel, and (3) exercise and air travel.
      In addition, the review examines confounding variables that may contribute to
      coagulation and strategies to prevent blood clot formation after exercise and
      during air travel.

PMID- 30282094
TI  - The Use of Health Information Exchange to Augment Patient Handoff in Long-Term
      Care: A Systematic Review.
AB  - BACKGROUND:  Legislation aimed at increasing the use of a health information
      exchange (HIE) in healthcare has excluded long-term care facilities, resulting in
      a vulnerable patient population that can benefit from the improvement of
      communication and reduction of waste. OBJECTIVE:  The purpose of this review is
      to provide a framework for future research by identifying themes in the long-term
      care information technology sector that could function to enable the adoption and
      use of HIE mechanisms for patient handoff between long-term care facilities and
      other levels of care to increase communication between providers, shorten length
      of stay, reduce 60-day readmissions, and increase patient safety. METHODS:  The
      authors conducted a systematic search of literature through CINAHL, PubMed, and
      Discovery Services for Texas A&M University Libraries. Search terms used were
      ("health information exchange" OR "healthcare information exchange" OR "HIE") AND
      ("long term care" OR "long-term care" OR "nursing home" OR "nursing facility" OR
      "skilled nursing facility" OR "SNF" OR "residential care" OR "assisted living").
      Articles were eligible for selection if they were published between 2010 and
      2017, published in English, and published in academic journals. All articles were
      reviewed by all reviewers and literature not relevant to the research objective
      was excluded. RESULTS:  Researchers selected and reviewed 22 articles for common
      themes. Results concluded that the largest facilitator and barrier to the
      adoption of HIE mechanisms is workflow integration/augmentation and the
      organizational structure/culture, respectively. Other identified facilitator
      themes were enhanced communication, increased effectiveness of care, and patient
      safety. The additional barriers were missing/incomplete data, inefficiency, and
      market conditions. CONCLUSION:  The long-term care industry has been left out of
      incentives from which the industry could have benefited tremendously.
      Organizations that are not utilizing health information technology mechanisms,
      such as electronic health records and HIEs, are at a disadvantage as insurers
      switch to capitated forms of payment that rely on reduced waste to generate a
      profit.

PMID- 30282096
TI  - Onlay Reconstruction of the Posterior Cruciate Ligament: Biomechanical Comparison
      of Unicortical and Bicortical Tibial Fixation.
AB  - Posterior cruciate ligament (PCL) injuries are generally associated with high
      energy trauma. There are many controversies regarding optimal surgical technique
      in regard to graft selection and fixation methods. The recently described onlay
      technique allows for direct fixation of a hamstring autograft to the posterior
      aspect of the tibia with cancellous screw and spiked washer, while protecting the
      neurovascular structures and avoiding the so-called "killer turn." The objective
      of this study was to compare immediate postimplantation biomechanics of
      unicortical versus bicortical tibial fixation of onlay PCL grafts. Eight knees
      were randomly assigned to one of two onlay PCL techniques (n = 4
      knees/technique), performed by a single experienced surgeon. Testing consisted of
      a posterior-directed force at four knee flexion angles, 10, 30, 60, and 90
      degrees, to measure load to 5 mm of posterior displacement, maximum displacement
      (at 100 N load), and stiffness. For statistical analyses, data for each knee were
      normalized to the native PCL-intact knee and were then grouped into unicortical
      or bicortical groups accordingly. Data for load to 5 mm (strength), displacement
      at 100 N, and stiffness were compared among PCL-intact, PCL-deficient,
      unicortical fixation, and bicortical fixation categories using one-way analysis
      of variance to assess for statistically significant (p < 0.05) differences. When
      compared with PCL-deficient knees, both fixation techniques had less laxity. When
      compared with PCL-intact knees, unicortical had more laxity at all angles, and
      bicortical had more laxity only at 90 degrees (p < 0.001). For relative graft
      strength, intact knees required significantly higher loads than both treatment
      groups. Bicortical, however, outperformed unicortical at all angles (p < 0.001)
      for relative strength. Regarding stiffness, there were no significant differences
      between unicortical and bicortical, and both were superior to PCL-deficient and
      inferior to PCL-intact knees. Based on cadaveric biomechanical testing, none of
      the reconstructed PCL knees was able to replicate the intact native PCL, but both
      techniques were superior to PCL-deficient knees. The bicortical tibial fixation
      technique appears to have biomechanical advantages when opting for onlay PCL
      reconstruction.

PMID- 30282097
TI  - All-Polyethylene Tibial Components in Total Knee Replacement: Early Failures.
AB  - In total primary knee replacement surgery, the use of all-polyethylene tibial
      (APT) components has many advantages, including no backside wear and no linear
      dissociation. In addition, the greater polyethylene thickness permits more
      conservative bone resection compared with that for metal-backed components, with
      a lower unit cost and similar functional results. Thus, the use of an APT in
      primary total knee arthroplasty remains an attractive option. This is a review of
      158 patients who underwent primary knee replacement using APT components from a
      single manufacturer. Data collection included age, American Society of
      Anesthesiology physical status classification, body mass index (BMI), type of
      deformity, the presence of diabetes mellitus, rate of revision, and
      characteristics associated with early failure of the components. Average follow
      up time was 40 months. The revision rate for any reason was 5.6%, and the average
      BMI in revision cases was 37.6. Patients with a higher BMI (>= 37.6) were
      significantly more likely to require revision surgery than patients with a lower
      BMI (p = 0.04). In our sample, high BMI was a contributing factor for early
      failures in total knee replacements using an APT component. Generally,
      polyethylene tibial components used for primary knee replacements are safe and
      effective, with good outcomes and subsequent lower costs to the health care
      system.

PMID- 30282098
TI  - Periprosthetic Fracture following Partial Knee Arthroplasty.
AB  - Partial knee arthroplasty is a procedure with long-term successful outcomes.
      However, there are several potential complications including retained cement
      fragments, bearing dislocation, infection, component loosening, medial collateral
      ligament injury, and overcorrection, leading to progressive arthritis.
      Periprosthetic fracture is an uncommon complication, with multiple reports
      showing an incidence of less than 1%. Hence, there are no established algorithms
      to guide treatment. A consecutive series of 2,464 patients who underwent partial
      knee arthroplasty between January 2009 and April 2017 was reviewed. We identified
      16 patients with early periprosthetic fracture, with an incidence of 0.6%. All of
      these were tibial fractures, which occurred at a mean of 35 days postoperatively.
      There were 5 males and 11 females, with an average age of 70 years at the time of
      surgery. Average follow-up was 62 months. Two patients had contralateral
      compartment insufficiency fractures that were successfully treated
      nonoperatively, five patients immediately underwent total knee arthroplasty
      (TKA), and nine patients underwent open reduction internal fixation (ORIF). Two
      of these cases had a failed ORIF and required conversion to TKA. Seven patients
      were successfully treated with a medial buttress plate in compression. Average
      Knee Society Score at final follow-up was 81, and average flexion was 115
      degrees, with no patients having greater than 5-degree flexion contracture.
      Periprosthetic fracture following partial knee arthroplasty resulted in a high
      rate of conversion TKA. However, ORIF in select patients resulted in fracture
      healing and retention of the partial knee replacement. All patients were
      successfully treated with low complication rates, excellent range of motion, and
      acceptable knee scores at final follow-up.

PMID- 30282099
TI  - Clinical Results after Combined Distal Femoral Osteotomy in Patients with
      Patellar Maltracking and Recurrent Dislocations.
AB  - The purpose of this study is to analyze the clinical results after treatment of
      patellofemoral instability and maltracking caused by torsional or axial
      deformities of the lower extremity by combined distal femoral osteotomies (DFOs).
      We analyzed 31 DFOs (25 patients) with patellar maltracking and instability,
      treated in our clinic. Torsional angles and the leg axis in the frontal plane
      were measured preoperatively. Standardized scoring systems were determined pre-
      and postoperatively including a clinical examination. Nineteen cases of torsional
      and 12 cases of axis deformities were evaluated 27 (12-64) months
      postoperatively. Among those with torsional deformity, mean femoral torsion was 
      39.0 +/- 8.8 degrees, tibial tuberosity to trochlear groove (TT-TG) 20.3 +/- 4.5
      mm. We performed 19 torsional (+11.4 +/- 2.4 degrees) DFOs with medial
      patellofemoral ligament (MPFL) augmentation (n = 19), tibial tuberosity transfer
      (n = 14, 10.9 +/- 6.0 mm), varus (n = 4, 3.3 +/- 1.0 degrees), or valgus (n = 1,
      7.0 degrees) correction. Among valgus deformities, the leg axis was 6.7 +/- 2.3
      degrees valgus and TT-TG 19.3 +/- 5.0 mm. We performed 12 medially closing-wedge
      DFOs (7.6 +/- 2.8 degrees) with MPFL augmentation (n = 12) and tibial tubercle
      transfer (n = 9, 11.4 +/- 7.3 mm). Visual analogue pain scale improved from 6.2
      to 1.5 (p = 0.000), Kujala score from 45.0 to 81.5 (p = 0.000), Lysholm score
      from 40.3 to 83.9 (p = 0.000), and Tegner score from 2.1 to 3.9 (p = 0.000).
      Preoperative cartilage damage significantly influences the postoperative
      functional outcome (Lysholm score) (p = 0.026) as well as the improvement in
      terms of the Kujala score (p = 0.045) in the overall collective. No redislocation
      was observed. Patellofemoral maltracking and instability in torsional and axis
      deformities can successfully be treated by combined DFOs with excellent clinical
      results. The coexistence of risk factors for patellar instability requires a
      combination of additional procedures to complement the osteotomy. Preoperative
      cartilage lesions significantly influence the clinical outcome.

PMID- 30282100
TI  - Effects of an Intervention to Improve Life-Space Mobility and Self-Efficacy in
      Patients following Total Knee Arthroplasty.
AB  - Life-space mobility describes the spatial areas through which an individual
      moves, and the frequency and need for assistance. Although patients with knee
      osteoarthritis (OA) have shown restricted life-space mobility, total knee
      arthroplasty (TKA) does not improve it beyond preoperative levels. Life-space
      mobility after TKA was influenced by self-efficacy for walking tasks; thus, an
      intervention to improve self-efficacy for walking tasks may contribute to better
      life-space mobility. We provided a walking event including several walking tasks
      as the intervention. We assessed the effect of the walking event on life-space
      mobility and self-efficacy for walking tasks in patients following TKA. In this
      nonrandomized controlled trial, patients who underwent primary TKA were
      recruited. After recruitment, patients who could not participate in the walking
      event due to scheduling conflicts were included in the control group. The walking
      event consisted of 3.5 km of walking course and included walking tasks as
      follows: crossing at the crosswalk, walking up- and downstairs without a railing,
      walking along dirt roads, and walking up and down a slope. The primary outcome
      was life-space mobility measured using Life-Space Assessment (LSA) and self
      efficacy for walking tasks measured using the modified Gait Efficacy Scale
      (mGES). We enrolled 104 patients, of whom 36 were assigned to the intervention
      group and participated in the walking event. Participants in the intervention
      group had significantly better LSA score (adjusted mean difference between
      groups: 13.9; 95% confidence interval: 12.4-15.5; p < 0.001) and mGES score
      (adjusted mean difference between groups: 13.8; 95% confidence interval: 12.4
      15.1; p < 0.001) than the control group even after adjusting for age, gender,
      body mass index, elapsed time from surgery, the severity of knee OA of
      nonoperated limb, and patient-reported functional outcome. The walking event
      including various walking tasks improved life-space mobility and self-efficacy in
      patients following TKA. It is important to design a program that can improve self
      efficacy for walking tasks through mastery experiences to improve life-space
      mobility after TKA.

PMID- 30282101
TI  - Effect of Femoral Antetorsion on Tibiofemoral Translation and Rotation in the
      Anterior Cruciate Ligament Deficient Knee.
AB  - We aimed to investigate how increased or decreased femoral antetorsion would
      affect the biomechanics of the knee in an anterior cruciate ligament (ACL)
      deficient cadaveric model. We hypothesized that external or internal rotation of
      the distal femur, achieved through a femoral osteotomy, would affect the
      magnitude of tibiofemoral translation and rotation. Navigated measurements of
      tibiofemoral translation and rotation during the anterior drawer, Lachman, and
      pivot shift tests were performed on six whole-body cadaveric specimens in each of
      the following four conditions: native, ACL-deficient knee, ACL-deficient knee and
      20-degree internal distal femur rotation, and ACL-deficient knee and 20-degree
      external distal femur rotation. Increased femoral antetorsion significantly
      reduced anterior tibial translation in the ACL-deficient knee during the anterior
      drawer, Lachman, and pivot shift tests (p < 0.05). Conversely, decreasing femoral
      antetorsion resulted in an increase in anterior tibial translation in the
      anterior drawer (nonsignificant), Lachman (p < 0.05), and pivot shift (p < 0.05)
      tests. Internally rotating the distal femur significantly reduced the magnitude
      of tibial rotation during the pivot shift test in the ACL-deficient knee (p <
      0.05), whereas external rotation of the distal femur significantly increased
      tibial rotation (p < 0.05). The magnitude of femoral antetorsion affects
      tibiofemoral translation in an ACL-deficient cadaveric mode. Internally rotating
      the distal femur 20 degrees reduced the magnitude of tibial translation and
      rotation similar to that of the native knee, whereas externally rotating the
      distal femur aggravated translational and rotational instability.

PMID- 30282102
TI  - Albumin, Prealbumin, and Transferrin May Be Predictive of Wound Complications
      following Total Knee Arthroplasty.
AB  - Nutritional status has become increasingly important in optimizing surgical
      outcomes and preventing postoperative infection and wound complications. However,
      currently, there is a paucity in the orthopaedics literature investigating the
      relationship between nutritional status and wound complications following total
      knee arthroplasty (TKA). Therefore, the purpose of this study was to determine
      the prevalence of (1) postoperative infections, (2) wound complications, (3)
      concomitant infection with wound (CoIW) complication, and (4) infection followed
      by wound complication by using (1) albumin, (2) prealbumin, and (3) transferrin
      levels as indicators of nutritional status. These four different outcome measures
      were chosen as they are encountered commonly in daily clinical practice. A
      retrospective review of a national private payer database for patients who
      underwent TKA with postoperative infections and wound complications stratified by
      preoperative serum albumin (normal: 3.5-5 g/dL), prealbumin (normal: 16-35
      mg/dL), and transferrin levels (normal: 200-360 mg/dL) between 2007 and 2015 was
      conducted. Patients were identified by Current Procedural Terminology (CPT),
      International Classification of Disease, ninth revision (ICD-9) codes, and
      Logical Observation Identifiers Names and Codes (LOINC). Linear regression was
      performed to evaluate changes over times. Yearly rates of infection, as well as a
      correlation and odds ratio analysis of nutritional laboratory values to
      postoperative complications, were also performed. Our query returned a total of
      161,625 TKAs, of which 11,047 (7%) had postoperative wound complications, 18,403
      (11%) had infections, 6,296 (34%) had CoIW, and 4,877 (4%) patients with
      infection developed wound complications. Albumin was the most commonly ordered
      laboratory test when assessing complications (96%). Wound complications,
      infections, CoIW, and infection with wound complications after were higher in
      those below the normal range: albumin <3.5 g/dL (9, 14, 6, and 5%), prealbumin
      <15 mg/dL (20, 23, 13, and 12%), and transferrin <200 mg/dL (12, 17, 6, and 6%).
      Preoperative albumin, prealbumin, and transferrin values falling below the normal
      range represented an increased risk for postoperative complications. Those
      patients who were in the normal range, however, did not have an increased risk.
      Therefore, our results suggest that preoperative nutritional optimization can
      play an important role in reducing the risk for postoperative complications.

PMID- 30282104
TI  - Association between Gestational Weight Gain Adequacy and Adverse Maternal and
      Neonatal Outcomes.
AB  - OBJECTIVES:  To estimate the prevalence of gestational weight gain (GWG) adequacy
      according to the 2009 guidelines, and to examine the association between GWG
      adequacy and the adverse outcomes, stratified by prepregnancy body mass index
      (BMI). STUDY DESIGN:  A retrospective cohort study, using the 2011 to 2013 U.S.
      linked birth/infant death datasets, restricted to nonanomalous singleton live
      births at 37 to 41 weeks. The adverse outcomes included composite maternal
      morbidity (CMM), composite neonatal morbidity (CNM), and neonatal and infant
      mortalities. We used multivariable Poisson's regression models with robust error
      variance to examine the association between GWG adequacy and adverse outcomes.
      RESULTS:  Of 8,656,791 singleton live births, 20, 32, and 48% had inadequate,
      adequate, and excessive GWG, respectively. After multivariable regression
      adjustment, compared with adequate GWG, excessive GWG had 1.10 (1.08-1.13) and
      1.12 (1.10-1.14) times higher risk of CMM and CNM, respectively; similar findings
      were observed in BMI subgroups. Compared with adequate GWG, inadequate GWG had
      1.14 (1.03-1.26) and 1.12 (1.07-1.18) times higher risk of neonatal and infant
      mortalities, respectively. Similar results were noted among women with normal
      weight. CONCLUSION:  Excessive GWG was associated with an increased risk of CMM
      and CNM, while inadequate GWG was associated with a higher risk of neonatal and
      infant mortalities.

PMID- 30282103
TI  - Risk of Ischemic Placental Disease in Relation to Family History of Preeclampsia.
AB  - OBJECTIVE:  To assess the risk of ischemic placental disease (IPD) including
      preeclampsia, small for gestational age (SGA), and abruption, in relation to
      preeclampsia in maternal grandmother, mother, and sister(s). STUDY DESIGN:  We
      performed a secondary analysis of data from a randomized trial of vitamins C and
      E for preeclampsia prevention. Data on family history of preeclampsia were based
      on recall by the proband. The associations between family history of preeclampsia
      and the odds of IPD were evaluated from alternating logistic regressions.
      RESULTS:  Of the 9,686 women who delivered nonmalformed, singleton live births,
      17.1% had IPD. Probands provided data on preeclampsia in 55.5% (n = 5,374) on all
      three family members, 26.5% (n = 2,562) in mother and sister(s) only, and 11.6%
      (n = 1,125) in sister(s) only. The pairwise odds ratio (pOR) of IPD was 1.16 (95%
      confidence interval [CI]: 1.00-1.36) if one or more of the female relatives had
      preeclampsia. The pORs of preeclampsia were 1.54 (95% CI: 1.12-2.13) and 1.35
      (95% CI: 1.03-1.77) if the proband's mother or sister(s) had a preeclamptic
      pregnancy, respectively, but no associations were seen for SGA infant or
      abruption. CONCLUSION:  This study suggests that IPD may share a predisposition
      with preeclampsia, suggesting a familial inheritance.

PMID- 30282105
TI  - PaO2/FiO2 Ratio as Predictor of Mortality in Neonates with Meconium Aspiration
      Syndrome.
AB  - OBJECTIVES:  Partial arterial pressure of oxygen/fraction of oxygen in inspired
      air (PaO2/FiO2) ratio has been used as a predictor of outcome in some neonatal
      conditions, but has not been used in meconium aspiration syndrome (MAS). This
      study was conducted with the objective to study if the PaO2/FiO2 ratio of < 200
      at 6, 12, and 24 hours of life can predict mortality in neonates with MAS. STUDY
      DESIGN:  Two hundred neonates with MAS were included in the study. PaO2/FiO2
      ratio was calculated at 6, 12, and 24 hours of life. Sensitivity, specificity,
      predictive values, and likelihood ratio at cut-off < 200 to predict mortality was
      calculated. RESULTS:  PaO2/FiO2 ratio at cut-off of < 200 was found to predict
      mortality in neonates with MAS with 94.1% sensitivity and 96.6% specificity. It
      was also able to predict development of severe MAS. CONCLUSION:  PaO2/FiO2 at <
      200 can predict all-cause mortality in neonates with MAS. It can be used as vital
      tool in identifying newborns at high risk, thus helping in focused care.

PMID- 30282106
TI  - The Role of Umbilical Cord Blood Concentration of IGF-I, IGF-II, Leptin,
      Adiponectin, Ghrelin, Resistin, and Visfatin in Fetal Growth.
AB  - OBJECTIVE:  Herein, we measured the concentration of insulinlike growth factor I
      (IGF-I), IGF-II, leptin, adiponectin, ghrelin, resistin, and visfatin in the
      umbilical cord blood of newborns categorized as "small for gestational age"
      (SGA), "appropriate for gestational age" (AGA), and "large for gestational age"
      (LGA). Our aim was to elucidate the link between the levels of these proteins and
      fetal growth. STUDY DESIGN:  A total of 96 term infants were included and
      categorized into three weight categories. Their venous cord blood samples were
      collected to measure the levels of IGF-I, IGF-II, leptin, adiponectin, ghrelin,
      resistin, and visfatin. RESULTS:  IGF-I, visfatin, and leptin levels showed
      significant differences among the groups. Pairwise comparisons showed that
      adiponectin (p = 0.023), resistin (p = 0.025), and ghrelin (p = 0.005) levels
      were significantly lower in the SGA group than in the LGA group. Correlation
      analyses showed a strong association of IGF-1, IGF-II, and leptin levels with
      birth weight (r = 0.644, p < 0.001; r = 0.441, p < 0.001; and r = 0.404, p <
      0.001, respectively). CONCLUSION:  SGA newborns showed a significantly higher
      visfatin concentration and lower ghrelin, leptin, resistin, and adiponectin
      levels than the AGA and LGA newborns did.

PMID- 30282107
TI  - Time to Delivery after Scheduled Shirodkar Cerclage Removal in Singleton
      Gestations based on the Original Indication for Cerclage Placement.
AB  - OBJECTIVE:  To estimate the time to delivery after elective cerclage removal and
      evaluate whether there is a difference based on the indication for cerclage
      placement. STUDY DESIGN:  This was a retrospective cohort of singleton
      pregnancies that underwent Shirodkar cerclage placement at a single maternal
      fetal medicine practice between June 2005 and June 2017. We included all
      scheduled elective cerclage removals >36 weeks. The primary outcome was latency
      to delivery. We further compared time to delivery based on the original
      indication for cerclage. Data were analyzed using the one-way analysis of
      variance and chi-square test. RESULTS:  A total of 143 patients met the inclusion
      criteria. Of these, 40.6% were history indicated, 51.0% ultrasound indicated, and
      8.4% exam indicated. The mean time from removal to delivery was 13.3 +/- 8.4
      days; 12.6% (18/136) of patients delivered within 24 hours of removal. When
      stratified by indication for cerclage, there were no significant differences for
      all delivery outcomes. Delaying cerclage removal to >37 weeks resulted in a
      statistically significantly later gestational age at delivery compared with
      removal between 36 and 366/7 weeks (39.0 vs. 38.3 weeks, p = 0.001). CONCLUSION: 
      The mean time from elective Shirodkar cerclage removal to delivery is 13 days
      with only 12.6% of patients delivering within 24 hours of removal.

PMID- 30282108
TI  - Risk of Cesarean Delivery among Nulliparous Asian-Indian Women with Term
      Singleton Pregnancies.
AB  - OBJECTIVE:  Asian-Indian women are a growing population in the United States, but
      little data exist about their risk of cesarean delivery (CD). We characterize the
      odds of CD among Asian-Indian women and determine whether neonatal birth weight
      modifies this relationship. STUDY DESIGN:  This is a retrospective cohort study
      using an administrative perinatal database from California. We identified
      1,029,940 nulliparous women with live, singleton, nonanomalous deliveries between
      37 and 42 completed weeks of gestation. We performed multivariable logistic
      regression analyses to determine if Asian-Indian women were more likely to
      deliver by CD, compared with white non-Hispanic women, adjusting for
      sociodemographic and clinical variables. We explored if birth weight was an
      effect modifier, testing the interaction term's significance using Wald's test,
      and performed multivariable logistic regressions stratified by birth weight
      category. RESULTS:  Asian-Indian women comprised 2.0% of the cohort. Compared
      with white non-Hispanic women, Asian-Indian women had an adjusted odds of 1.41
      (95% confidence interval: 1.36-1.46) for CD. However, we noted effect
      modification of birth weight on the odds of CD by race/ethnicity (p < 0.001).
      Among all birth weight categories exceeding 3,000 g, Asian-Indian women had
      higher odds of CD than white non-Hispanic women. CONCLUSION:  Asian-Indian women
      are at greater risk of CD than white non-Hispanic women when birthweight exceeds
      3,000 g.

PMID- 30282109
TI  - Post-traumatic stress disorder in Stevens-Johnson syndrome and toxic epidermal
      necrolysis: prevalence and risk factors. A prospective study of 31 patients.
AB  - BACKGROUND: Epidermal necrolysis is a rare and severe cutaneous adverse reaction
      to drugs with long-term somatic consequences and potentially underrecognized
      psychological complications. OBJECTIVES: To assess the prevalence and risk
      factors of post-traumatic stress disorder (PTSD) in Stevens-Johnson syndrome
      (SJS) and toxic epidermal necrolysis (TEN) in a population of adults undergoing
      psychiatric evaluation. METHODS: In this prospective study, we included adult
      patients admitted at the acute phase of SJS/TEN to our dermatology department
      from June 2009 to February 2013. The main objective was to assess the prevalence
      of PTSD at 6 months after the acute disease phase, defined by a PTSD Checklist
      score > 44. Secondary objectives were to investigate risk factors of PTSD in the
      medical history of patients and characteristics of the disease at the acute phase
      by the Peritraumatic Dissociative Experience Questionnaire (PDEQ) and
      Peritraumatic Distress Inventory (PDI) and the degree of impairment on the
      Sheehan Disability Scale. RESULTS: We initially included 32 of 80 patients
      admitted during the study period. At 6 months, seven of 30 still followed up had
      a PTSD Checklist score > 44, suggesting a PTSD prevalence of 23%; 23 (77%)
      patients had a hydroxyzine prescription at the acute phase. The main risk factors
      associated with PTSD at 6 months were psychological results at the acute phase.
      CONCLUSIONS: Despite frequent prescription of hydroxyzine at the acute phase,
      almost one-quarter of patients with SJS/TEN had PTSD at 6 months. A systematic
      psychiatric evaluation should be offered regularly for at least 1 year after the
      acute disease phase.

PMID- 30282110
TI  - Relationship between local presence and density of Aedes aegypti eggs with dengue
      cases: a spatial analysis approach.
AB  - OBJECTIVES: To analyze the relationship between the occurrence of dengue and
      ovitrap positivity and dengue egg density in two Amazonas municipalities (Brazil)
      in 2016. METHODS: We performed a case-control study using secondary data from the
      dengue fever surveillance system. Ovitraps distributed regularly in the urban
      area of two cities were used to monitor the presence of the vector. The
      relationship between egg positivity, egg density and the location of dengue cases
      was evaluated using two approaches as follows: (i) based on the result of the
      nearest neighbour ovitrap and (ii) based on the results of the set of ovitraps
      within the influence area of 300 m from the location of each case and control.
      RESULTS: During the study period, 229 confirmed cases of dengue fever were
      reported in Tabatinga and 89 cases in Itacoatiara. In this study, we found that
      the positivity of ovitraps was related to the occurrence of dengue in Tabatinga
      and Itacoatiara. An association between egg density of Ae. aegypti and dengue
      occurrence was also observed in Itacoatiara. The temporal lags for ovitrap
      positivity measurements were predominantly 15 or 30 days. A dengue association
      for egg density for a 15-day time lag was detected for one of the case-control
      approaches. CONCLUSIONS: The location of dengue cases is related to ovitrap egg
      positivity, while a less evident possible association may exist for egg density.
      This indicates that these traps could be used to improve vector control actions.

PMID- 30282111
TI  - Understanding the patient's experience of care in idiopathic pulmonary fibrosis.

PMID- 30282112
TI  - Intrapatient variability in tacrolimus trough levels after solid organ
      transplantation varies at different postoperative time periods.

PMID- 30282113
TI  - Linkage to care and antiretroviral therapy initiation by testing modality among
      individuals newly diagnosed with HIV in Tanzania, 2014-2017.
AB  - OBJECTIVE: To measure linkage to care and antiretroviral therapy (ART) initiation
      among newly diagnosed individuals with HIV in a rural Tanzanian community.
      METHODS: We included all new HIV diagnoses of adults made between 2014 and 2017
      during community- or facility-based HIV testing and counselling (HTC) in a rural
      ward in northwest Tanzania. Community-based HTC included population-level HIV
      serological testing (sero-survey), and facility-based HTC included a stationary,
      voluntary HTC clinic (VCT) and an antenatal clinic (ANC) offering provider
      initiated HTC (ANC-PITC). Cox regression models were used to compare linkage to
      care rates by testing modality and identify associated factors. Among those in
      care, we compared initial CD4 cell counts and ART initiation rates by testing
      modality. RESULTS: A total of 411 adults were newly diagnosed, of whom 10%
      (27/265 sero-survey), 18% (3/14 facility-based ANC-PITC) and 53% (68/129 facility
      based VCT) linked to care within 90 days. Individuals diagnosed using facility
      based VCT were seven times (95% CI: 4.5-11.0) more likely to link to care than
      those diagnosed in the sero-survey. We found no difference in linkage rates
      between those diagnosed using facility-based ANC-PITC and sero-survey (P = 0.26).
      Among individuals in care, 63% of those in the sero-survey had an initial CD4
      count >350 cells/mm3 vs. 29% of those using facility-based VCT (P = 0.02). The
      proportion who initiated ART within 1 year of linkage to care was similar for
      both groups (94% sero-survey vs. 85% facility-based VCT; P = 0.16). CONCLUSIONS:
      Community-based sero-surveys are important for earlier diagnosis of HIV-positive
      individuals; however, interventions are essential to facilitate linkage to care.

PMID- 30282114
TI  - Multi-Objective Genetic Algorithm Assisted by an Artificial Neural Network
      Metamodel for Shape Optimization of a Centrifugal Blood Pump.
AB  - A centrifugal blood pump is a common type of the pump used as a left ventricular
      assist device (LVAD) in the medical industries. The reduction of the LVADs
      hemolysis level to reduce the blood damage is one of the major concerns in
      designing of such devices. Also, the enhancement of the LVADs efficiency to
      decrease the battery size is another design requirement. The blood damage
      critically depends on the state of the blood being pumped. Besides the blood
      state, the blood damage also depends on the pump impeller and volute geometries.
      In this research, a multi-objective optimization of a centrifugal blood pump is
      performed. A complete 3D-optimization platform is established for both impeller
      and volute of a centrifugal blood pump consisting of parametric modeling,
      automatic mesh generation, computational fluid dynamics (CFD) simulation, and
      optimization strategy. A vast number of cases with various impeller and volute
      shapes are numerically simulated. Three different metamodels are created using
      artificial neural networks (ANNs) in order to approximate the pump hydraulic
      efficiency, hemolysis index (HI), and pressure head. The inverse of the relative
      pressure head is defined as the first objective and the summation of relative
      hemolysis index and the inverse of the relative efficiency is assumed as the
      second objective. Non-dominated Sorting Genetic Algorithm-II (NSGA-II) is used to
      find the Pareto Front. A set of optimal points is selected. Finally, for the
      physiological flow conditions, the optimum design that provides 11.9% HI
      reduction and 7.2% efficiency enhancement is selected.

PMID- 30282115
TI  - Comparison between the traditional (1997) and revised (2009) WHO classifications
      of dengue disease: a retrospective study of 30 670 patients.
AB  - OBJECTIVE: To compare WHO's traditional (1997) and revised (2009) guidelines for
      dengue classification, using a large sample of patients of all ages with varying
      clinical conditions from a dengue-endemic area in Brazil. METHODS: We compared 30
      670 laboratory-confirmed dengue cases (1998-2012) using both WHO's dengue
      classification guidelines. Stereotype ordinal logistic regressions were used to
      analyse the association between patients' demographics and signs and symptoms
      related to dengue infection severity, as defined in the 1997 and 2009 guidelines.
      We then compared the degree of agreement in dengue classification of both
      guidelines. RESULTS: Dengue signs and symptoms in patients were poorly correlated
      to disease severity as defined by both guidelines (Cramer's V test <0.2).
      Hypotensive shock was the exception for both classifications, presenting
      dependence (Z = 56.42; P < 0.001, and Z = 55.24; P < 0.001) and high agreement
      (Cramers's V = 1; P < 0.001, and Cramers's V = 0.97; P < 0.001) for WHO 1997 and
      2009, respectively. Last, we also found substantial agreement in disease
      classification between both guidelines (Kendall tau-b = 0.79; P < 0.001),
      although 2009 guidelines were more sensitive in the detection of severe cases.
      CONCLUSIONS: We hope our results will inform the debate about dengue
      classification guidelines, particularly concerning clinical value, study
      comparability, and ways in which future guidelines can support the clinical
      management of dengue. Our results suggest that caution should be taken when using
      WHO guidelines to assess dengue severity to improve clinical management of
      patients.

PMID- 30282116
TI  - The contribution of respiratory microbiome analysis to a treatable traits model
      of care.
AB  - The composition of the airway microbiome in patients with chronic airway
      diseases, such as severe asthma, chronic obstructive pulmonary disease (COPD),
      bronchiectasis and cystic fibrosis (CF), has the potential to inform a precision
      model of clinical care. Patients with these conditions share overlapping disease
      characteristics, including airway inflammation and airflow limitation. The
      clinical management of chronic respiratory conditions is increasingly moving away
      from a one-size-fits-all model based on primary diagnosis, towards care targeting
      individual disease traits, and is particularly useful for subgroups of patients
      who respond poorly to conventional therapies. Respiratory microbiome analysis is
      an important potential contributor to such a 'treatable traits' approach,
      providing insight into both microbial drivers of airways disease, and the
      selective characteristics of the changing lower airway environment. We explore
      the potential to integrate respiratory microbiome analysis into a treatable
      traits model of clinical care and provide a practical guide to the application
      and clinical interpretation of respiratory microbiome analysis.

PMID- 30282117
TI  - Venoarterial Extracorporeal Membrane Oxygenation Increased Immune Function of
      Spleen and Decreased Reactive Oxygen Species During Post-Resuscitation.
AB  - We aimed to investigate the effect of venoarterial extracorporeal membrane
      oxygenation (VA-ECMO) on immune function of the spleen and reactive oxygen
      species (ROS) during post-resuscitation in a porcine model. After 8 min of
      untreated ventricular fibrillation and 6 min of basic life support, pigs were
      randomized into two groups: Group 1 received VA-ECMO and Group 2 received
      conventional cardiopulmonary resuscitation. After successful return of
      spontaneous circulation, the hemodynamic status was determined and blood samples
      were collected at 0, 1, 2, 4, and 6 h. Surviving pigs were euthanized 6 h after
      return of spontaneous circulation, their spleens were harvested and the T-cells
      were separated. Then, we investigated immune function parameters of the spleen
      and ROS levels. VA-ECMO increased the return of spontaneous circulation and 6 h
      survival rate after return of spontaneous circulation. Compared with the
      conventional cardiopulmonary resuscitation group, the VA-ECMO group showed
      increased superoxide dismutase and decreased malondialdehyde and ROS levels.
      Furthermore, VA-ECMO was associated with a high rate of CD4+ and CD4+/CD8+, high
      levels of interleukin 2, interferon gamma, and interferon gamma/interleukin 4, as
      well as high proliferation of lymphocytes. The apoptotic rate of T-cells was
      lower in the VA-ECMO group than it was in the conventional cardiopulmonary
      resuscitation group. VA-ECMO increased immune function of spleen and decreased
      ROS levels during post-resuscitation. Further research is expected to illustrate
      whether the differences in immune responses are due to ROS or some other
      perfusion related effect on spleen.

PMID- 30282118
TI  - Evaluating the use of a temperature sensor to monitor spectacle compliance in
      warm versus cold climates.
AB  - BACKGROUND: This study investigates the utility of a temperature sensor data
      logger to monitor spectacle compliance for future application in research and
      clinical settings. Specifically, the question of whether warm versus cold
      climates negatively impact accuracy of the sensor to monitor spectacle wear is
      investigated. METHODS: Fifty adults from Houston, Texas (summer) and 40 adults
      from Columbus, Ohio (winter) wore a thermosensor on their spectacles for one week
      while keeping wear-time logs. Temperatures during reported spectacle wear (ON)
      were compared to temperatures during non-wear (OFF) between sites. Two methods to
      approximate wear time were evaluated by percent error with respect to subject
      reported wear time. Method 1 filtered temperatures, classifying the range of 28.4
      to 35.2 degrees C as wear. Method 2 utilised examiners interpreting temperature
      versus time plots. Separate analysis of periods of reported outdoor wear was
      performed to identify the percentage of time examiners correctly identified wear.
      RESULTS: Group mean ON temperatures did not differ between sites (p = 0.72), but
      group mean OFF temperatures were significantly warmer in Houston (Houston: 24.7
      +/- 2.0 degrees C, Columbus: 20.3 +/- 2.1 degrees C; p < 0.0001). Median percent
      error of the filtering technique to approximate subject reported wear time was 4
      per cent for Houston and -8 per cent for Columbus. Median percent error for
      examiner 1: Houston 1 per cent, Columbus 0 per cent; median percent error for
      examiner 2: Houston 3 per cent, Columbus 0 per cent. Houston outdoor wear was
      correctly identified 88 and 97 per cent of the time by the examiners versus 79
      and 81 per cent for Columbus. CONCLUSION: Despite environmental temperature
      differences, measured temperatures during spectacle wear were similar across
      subjects and median percent error was less than 10 per cent for both wear time
      approximation methods. The device studied was effective for objectively
      monitoring spectacle wear in both warm and cold climates with the caveat that
      subjects spent the majority of time indoors.

PMID- 30282119
TI  - The relationship between the C-statistic and the accuracy of program-specific
      evaluations.
AB  - The C-statistic of the risk-adjustment model is often used to judge the accuracy
      of program evaluations. However, the C-statistic depends on the variability in
      risk for individual transplants and may be inappropriate for determining the
      accuracy of program evaluations. A simulation study investigated the association
      of the C-statistic with several metrics of program evaluation accuracy, including
      categorizing programs into the 5-tier system and identifying programs for
      regulatory review. The simulation study used data from deceased donor kidney
      alone transplants for adult recipients in the program-specific reports released
      January 2018. A range of C-statistics was generated by changing the variability
      in risk for individual transplants. The C-statistic had no association with any
      metric of program evaluation accuracy. Instead, the number of expected events at
      a program was the most important factor. For example, Spearman's rho, which is
      the correlation of ranks, was -0.27 and -0.72 between the true program-specific
      hazard ratios and assigned tiers for programs with, respectively, <3 and >10
      expected events. Presence of unadjusted risk factors did not modify the
      associations, although the accuracy of program evaluations was systematically
      lower. Therefore, the C-statistic provides no information on the accuracy of
      program evaluations.

PMID- 30282120
TI  - Transplant tourism complicated by life-threatening New Delhi metallo-beta
      lactamase-1 infection.
AB  - Transplant tourism, which is the practice of traveling to other countries for
      transplant, continues to be a major problem worldwide. We describe a patient who
      traveled to Pakistan and underwent commercial kidney transplant. He developed
      life-threatening infections from New Delhi metallo-beta-lactamase-1-producing
      Enterobacter cloacae and Rhizopus oryzae, resulting in a necrotizing kidney
      allograft infection and subsequent external iliac artery rupture. He survived
      after a prolonged course of nonstandardized antimicrobial therapy, including a
      combination of aztreonam and ceftazidime-avibactam, and aggressive surgical
      debridement with allograft nephrectomy. The early timing of infection with these
      unusual organisms localized to the allograft suggests contamination and
      substandard care at the time of transplant. This case highlights the challenges
      of caring for these infections and serves as a cautionary tale for the potential
      complications of commercial transplant tourism.

PMID- 30282121
TI  - Assessment of pattern and outcomes of pesticides poisoning in a tertiary care
      hospital.
AB  - OBJECTIVES: To assess the socio-demographic profile, pattern and treatment
      outcomes of pesticides poisoning. METHODS: A prospective observational study was
      conducted at the department of emergency medicine of a South Indian tertiary care
      hospital for 1.5 years to study the pattern and outcomes of poisoning cases due
      to pesticides. Level of significance (P) <0.05 was considered as statistically
      significant. RESULTS: A total of 375 poisoning victims with
      intentional/accidental exposure to pesticides were followed up and documented.
      The male-female ratio was 1:0.32; mean age was 31.65 +/- 13.10 years. 72% of
      cases were rural residents. Organophosphorus compounds were the most implicated
      pesticides. Mean Glasgow Comatose Score (GCS) of the patients was 12.22 +/- 3.86.
      80.3% of patients recovered while 6.4% died. About 13.3% patients were lost to
      follow-up as they were discharged against medical advice (DAMA). CONCLUSION:
      There was a statistical significance seen in the implication of pesticides for
      intentional poisoning with age, route of administration, area of residence and
      occupation of the victims. However, there was a strong association of the
      outcomes of poisoning with the toxic agent implicated for the poisoning.

PMID- 30282122
TI  - Hypothermic Machine Perfusion Versus Static Cold Storage in Deceased Donor Kidney
      Transplantation: A Systematic Review and Meta-Analysis of Randomized Controlled
      Trials.
AB  - Static cold storage (SCS) and hypothermic machine perfusion (HMP) are two primary
      options for renal allograft preservation. Compared with SCS, HMP decreased the
      incidence of delayed graft function (DGF) and protected graft function. However,
      more evidence is still needed to prove the advantages of the HMP. In this study,
      the outcomes of kidney grafts from the two preservation methods were compared by
      conducting a systematic review and meta-analysis. Randomized controlled trials
      (RCTs) comparing the effect of hypothermic machine perfusion and static cold
      storage in deceased donor kidney transplantation were identified through searches
      of the MEDLINE, EMBASE, and Cochrane databases between January 1, 1980 and
      December 30, 2017. The primary endpoints were delayed graft function and graft
      survival. Secondary endpoints included primary non-function (PNF), graft renal
      function, duration of DGF, acute rejection, postoperative hospital stay and
      patient survival. Summary effects were calculated as risk ratio (RR) with 95%
      confidence interval (CI) or mean difference (MD) with 95% confidence intervals
      (CI). A total of 13 RCTs were included, including 2048 kidney transplant
      recipients. The results indicated that compared with SCS, HMP decreased the
      incidence of DGF (RR 0.78, 95% CI 0.69-0.87, P < 0.0001), and improved the graft
      survival at 3 years (RR 1.06, 95% CI 1.02-1.11, P = 0.009). There was no
      significant difference in other endpoints. HMP might be a more desirable method
      of preservation for kidney grafts. The long-term outcomes of kidney allografts
      stored by hypothermic machine perfusion still need to be further investigated.

PMID- 30282123
TI  - Genome-wide association study reveals new loci involved in Arabidopsis thaliana
      and Turnip mosaic virus (TuMV) interactions in the field.
AB  - The genetic architecture of plant response to viruses has often been studied in
      model nonnatural pathosystems under controlled conditions. There is an urgent
      need to elucidate the genetic architecture of the response to viruses in a
      natural setting. A field experiment was performed in each of two years. In total,
      317 Arabidopsis thaliana accessions were inoculated with its natural Turnip
      mosaic virus (TuMV). The accessions were phenotyped for viral accumulation,
      frequency of infected plants, stem length and symptoms. Genome-wide association
      mapping was performed. Arabidopsis thaliana exhibits extensive natural variation
      in its response to TuMV in the field. The underlying genetic architecture reveals
      a more quantitative picture than in controlled conditions. Ten genomic regions
      were consistently identified across the two years. RTM3 (Restricted TEV Movement
      3) is a major candidate for the response to TuMV in the field. New candidate
      genes include Dead box helicase 1, a Tim Barrel domain protein and the eukaryotic
      translation initiation factor eIF3b. To our knowledge, this study is the first to
      report the genetic architecture of quantitative response of A. thaliana to a
      naturally occurring virus in a field environment, thereby highlighting relevant
      candidate genes involved in plant virus interactions in nature.

PMID- 30282125
TI  - We Ain't No Ways Tired: We Demand a Ban on the AR-15 Rifle Now.

PMID- 30282124
TI  - Apple rootstocks of different nitrogen tolerance affect the rhizosphere bacterial
      community composition.
AB  - AIMS: To select apple rootstocks that are tolerant to low nitrogen and reveal the
      relationship between the rhizosphere bacterial communities and the low nitrogen
      tolerance of the apple rootstock. METHODS AND RESULTS: In total, 235 lines of
      hybrids of Malus robusta Rehd. * M.9 with low nitrogen stress were cultivated in
      pots in a greenhouse equipped with a drip irrigation system, and growth
      characteristics, photosynthesis traits and mineral elements were monitored. The
      bacterial community structure of the rhizosphere from different rootstocks was
      determined via Illumina MiSeq sequencing. This study selected three low nitrogen
      tolerant (NT) lines that had higher nitrogen concentration, and higher
      photosynthesis rate than the three low nitrogen-sensitive (NS) lines. The
      bacterial community structure significantly differed (P <= 0.001) among the
      rootstocks. The bacterial phyla Proteobacteria and Actinobacteria were the
      dominant groups in the rhizosphere and presented higher abundance in the NT
      rhizosphere. The N concentration in the apple rootstocks exhibited highly
      positive Pearson correlations with the bacterial genera Sphingomonas,
      Pseudoxanthomonas, Bacillus and Acinetobacter, and negative correlations with the
      bacterial genera Pseudarthrobacter and Bradyrhizobium. CONCLUSIONS: This study
      showed that investigated rootstocks achieved increased nitrogen concentration by
      enhancing their photosynthetic production capacity and shaping their
      rhizobacteria community structure. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      findings provide a basis for studying the mechanisms of resistance to low
      nitrogen stress in apple rootstocks. Based on these beneficial bacteria,
      microbial inoculants can be developed for use in sustainable agricultural and
      horticultural production.

PMID- 30282126
TI  - African-American Women's Perceived Risk for Cardiovascular Disease versus
      Framingham Risk.
AB  - Cardiovascular disease (CVD) is the leading cause of death among African-American
      women in the United States. Accurate CVD risk perception may motivate these women
      to participate in health-promoting behaviors; however, perceived risk may not
      align with objective CVD risk. Our objective was to examine CVD risk perception,
      risk factors, and objective estimated risk (based on Framingham scores). This was
      a secondary data analysis of data collected from a 12-month lifestyle PA
      intervention conducted with 281 African-American women. Subjective perceived CVD
      risk was measured with two questions; CVD risks were examined via health
      assessment and self-questionnaire; and objective estimated CVD risk was
      calculated using the Framingham Risk score. Despite having several objective risk
      factors for CVD development, most participants perceived their CVD risk as low,
      and their Framingham scores were low. The Framingham Risk score may not be the
      best predictor of CVD risk for African-American women.

PMID- 30282127
TI  - Promoting Self-Management of Hypertension in the African-American Church.
AB  - Hypertension (HTN) continues to be one of the most preventable diseases that have
      global impact. The prevalence of HTN in African-Americans is considered to be
      among the highest in the world. This investigation sought to determine whether a
      church-based self-management program would aid African-American adults (18 years
      of age and above) in reducing their blood pressure (BP). The theoretical
      foundation was the Health Belief Model. The clinical question was: Will a church
      based American Heart Association (AHA) program on BP self-management decrease BP
      in African-American adults (aged 18 and above) who belong to a local Christian
      church? The quantitative methodology and pretest-posttest single group design
      were used in this investigation. The sample was a convenience sampling of 23
      Christian church members. The participants enrolled in the AHA's "Check. Change.
      Control(r). Tracker." There were only two demographic variables that were
      significant at the 0.05 level (2-tailed) with the initial BP: age was 0.585 (p =
      0.05) and having children was -0.434 (p = 0.039). The paired t-test was computed
      for the initial and final systolic BPs. The paired t-test for these variables was
      1.844 (p = 0.079). The paired t-test was computed for the initial and final
      diastolic BPs. The paired t-test for these variables was 1.724 (p = 0.079). These
      results indicated there were no improvements after the intervention. However,
      data supported clinical significance.

PMID- 30282128
TI  - Evaluating Relevance of Nursing Theories in Cross-Cultural and International
      Contexts.
AB  - Nursing has evolved over the past five decades in propagating the development of
      theoretical and empirical evidence through the application of nursing theories.
      The objective of this commentary is to stimulate scholarly debate focused on the
      development, application, and adaptation of nursing theory by nurse scientists,
      its relevance in the cross-cultural contexts, and to discuss future directions
      with a call to action using Leininger's seminal work on Culture Care Theory. The
      implicit nature of nursing theories preclude the optimal use and application in
      cross- cultural contexts because of the limitations in achieving conceptual,
      semantic, and operational equivalence. Work conducted by nurse scientists to date
      demonstrates that cultural values and beliefs are integral in cross-cultural
      contexts to enhance meaningful theory application for health interventions. More
      work is needed to advance nursing science through cross-cultural application of
      theories in research, practice, and education to optimize nursing theory
      adaptation in cross-cultural and international contexts.

PMID- 30282129
TI  - Using Case Study Methodology to Explore the Role of Discrimination in Workplace
      Incivility.
AB  - Exclusionary behaviors can be detrimental to the health and well-being of faculty
      in the workplace. When colleagues are judged by their peers because of the color
      of their skin, the language they speak, their gender, or who they choose to love
      (lesbian, gay, bisexual, transgender, asexual, or questioning), affected faculty
      are left emotionally and physically vulnerable. Institutions of higher learning
      must set standards of zero tolerance for faculty-to-faculty incivility. With
      standards taken from each faculty discipline, codes of conduct can be implemented
      not only at a departmental level, but also throughout the educational system.

PMID- 30282130
TI  - The Simultaneous Experiences of Being a Nurse Faculty Member and PhD Student: A
      Phenomenological Inquiry.
AB  - The demand for nursing faculty with doctoral degrees has prompted universities to
      devise strategies to hasten doctoral preparation. Insufficient preparation of
      nursing faculty negatively impacted the ability of colleges of nursing to enroll
      qualified applicants. In 2011, 75,000 applicants were turned away (AACN, 2012).
      Interview data from 11 participants were analyzed for themes and structure of
      meanings that led to a description of the essence of the phenomenon. Six related
      themes revealed the experiences of simultaneously being a nurse faculty member
      and PhD student. Starck's (2004) Middle Range Theory of Meaning provided a
      framework for gaining a deeper understanding of this phenomenon. The findings
      revealed the obstacles, sacrifices, pain, and rewards of being a nurse faculty
      member and PhD student simultaneously. The participants embraced numerous
      positive aspects including personal and professional growth. Therefore,
      understanding this experience is fundamental in eliciting support for the journey
      towards a PhD.

PMID- 30282131
TI  - How to Create a Telephone Follow-Up Program to Improve Glycemic Control in
      Uncontrolled Type 2 Diabetic African-American Women.
AB  - Type 2 diabetes is the seventh leading cause of death in the United States and
      this disease disproportionately affects African-Americans and other minorities.
      Diabetes self-management education has been shown through research to help
      patients achieve at-goal HgbA1c levels leading to a decrease in complications;
      however, patients do not attend these classes as much as they should. The
      creation of a telephone follow-up plan can be an option to improve glycemic
      control for the primary care clinician caring for uncontrolled Type 2 diabetic
      African-American females. The culturally sensitive content in the follow-up plan
      should focus on better nutrition management, increasing physical activity, and
      consistent glucose monitoring with increased skill in management of results. This
      telephone follow-up program is intended to help clinicians assist this population
      of patients to identify potential barriers using culturally sensitive content as
      a method of connecting with patients to help them achieve at-goal HgbA1c levels.

PMID- 30282132
TI  - The Growing Impact of Legionella in the Flint Water Crisis.
AB  - The water crisis in Flint, Michigan raised national awareness about lead- tainted
      drinking water, particularly its harm to children and pregnant and lactating
      women. However, according to recent findings, there may be another by-product of
      this man-made crisis. Failure to use anticorrosive material in the water, a
      practice mandated by the 1978 Clean Water Act, is being linked to an outbreak of
      Legionnaires' disease, an illness detrimental primarily to adults over 65 years
      of age. While Legionnaires' disease is relatively rare, it is also likely to
      remain undiagnosed. Clinicians, therefore, are urged to consider this diagnosis
      in adults with pneumonia that does not respond to typical antibiotic treatment,
      and in newborns with respiratory distress along with other non-typical symptoms
      as well as those who have had water births or who were exposed to ultrasonic,
      cool-mist humidification.

PMID- 30282133
TI  - Bump-Fire Stocks: Finding a Way to Outlaw Their Usage.

PMID- 30282134
TI  - Screening for Physical Activity and Cardiometabolic Risk Factors Among Rural
      African-American Women.
AB  - Physical inactivity can have major implications for cardiovascular disease and
      diabetes, which are leading causes of morbidity among African-American women.
      Recruiting in rural populations can present challenges and strategies that work
      in one community but may not be successful in another community. This study
      examined the feasibility, acceptability, and implementation of community-based
      screening using an abbreviated Racial and Ethnic Approaches to Community Health
      (REACH) Risk Factor self-report survey in a geographic region where these data
      were previously unavailable. Participants (N = 32) included African
      American/Black women, 21 years of age or older, who attended health screening
      events in a rural county in South Carolina. Findings from this study demonstrated
      the feasibility of community-based cardiometabolic risk screenings using an
      abbreviated REACH Risk Factor survey and linking participants to follow-up
      primary care. Findings also provide insight into recruitment strategies in this
      geographic region.

PMID- 30282135
TI  - Beauty for Ashes: A Church-Based Diabetes Care Program.
AB  - The pilot study described here was a test of interventions designed to enhance
      long-term disease management of African-Americans with type 2 diabetes in faith
      based organizations. A quasi-experimental design based on 46 participants was
      used comparing three interventions: guided imagery, group counseling, and routine
      care. Unexpectedly, the number of self-reported hypoglycemic episodes
      significantly increased in the Rational Emotive Behavioral Therapy (REBT) group,
      depressive symptoms significantly increased in the guided imagery group, and the
      mean hemoglobin A1c values did not significantly differ for any group. In future
      research, the authors will incorporate an interim step investigating the theory
      of integration (Hernandez, Antone, & Cornelius, 1999) to increase the explanatory
      power in assessing treatment effects of African-Americans in faith-based
      organizations.

PMID- 30282136
TI  - Being African-American, Obese, Female, and Residing in an Urban Area: The Lived
      Experience.
AB  - The objective of this qualitative study was to explore the experience of being
      African-American, obese, female, and residing in an urban area. Critical Social
      Theory of Black Feminist Thought guided the study framework and study questions.
      Within this framework, African-American women are multidimensional human beings
      with attitudes, habits, and personalities influenced by their religious beliefs,
      family, school, friends, and racial history. Interview data were obtained from 10
      women and analyzed using qualitative techniques. These individuals were aware of
      health consequences related to obesity and described barriers that inhibit
      healthy choices. Participant level of education provided the ability to avoid
      negative physical and social consequences associated with obesity.

PMID- 30282137
TI  - The Lived Experience of African-American Informal Caregivers of Family Members
      with Alzheimer's Disease and Related Dementias.
AB  - The purpose of this qualitative study was to describe the lived experience of
      African-American informal caregivers of family members with Alzheimer's Disease
      and Related Dementias (ADRD) in a home environment. Using a qualitative,
      phenomenological approach, a purposive sample of 16 African-American informal
      caregivers completed an in-depth interview that lasted from 30 to 60 minutes.
      Four themes emerged: (a) a sense of obligation, (b) an arduous journey, (c)
      sentinel events, and (d) faith in God. Findings indicated that caregivers needed
      to be well-informed concerning the demands of caregiving and needed more
      assistance with the task of delivering care. Informal caregivers lacked support,
      knowledge, and guidance. Implications for the discipline of nursing include
      emphasis on family assessment, teaching, awareness of resources, and
      collaboration with healthcare teams.

PMID- 30282138
TI  - The Root of Physical Inactivity Among African-American Women: Identifying
      Exercise Friendly Hairstyles.
AB  - The purpose of this study was to provide information regarding hair maintenance
      that would increase physical activity among African-American women. A descriptive
      study design was used, along with Survey Monkey to obtain online responses from
      African-American female participants over the age of 18 that were associated with
      four predominately African-American social organizations. Participants were asked
      to rate the "ease of use" of 8 hairstyles commonly worn by Black or African
      American women living in the United States as it related to three physical
      activity (PA) intensity categories: light to moderate, vigorous, and water-based
      physical activity. The results revealed that short natural styles had low
      maintenance scores for all three PA categories (1.19, 1.27, and 1.34,
      respectively). Increased knowledge and understanding of the complex and varied
      hair care practices common among African-American women will improve development
      of exercise-based health interventions for this population.

PMID- 30282139
TI  - Exploring Older Adults' Perceptions of the Utility and Ease of Use of Personal
      Emergency Response Systems.
AB  - The aim of this exploratory-descriptive study was to explore and describe
      perceptions of the utility and ease of use of personal emergency response systems
      (PERS) among older adults who are aging in place. This study explored the
      question of "What is the meaning of a PERS use for a functionally-impaired older
      adult?" Using an exploratory-descriptive qualitative design, 14 subjects were
      recruited in Queens, NY, who met the study's eligibility through the selection
      criteria. A 9-question in-person interview guide was used to conduct the face-to
      face, audio-taped, semi-structured interviews in an effort to gather information
      on the participants' experiences with using a PERS. Data were collected over a 2
      month period. While many participants admitted that they did not wear the PERS
      neck pendant or wrist device consistently, they still reported benefiting from
      having the button and participating in the program. Findings were consistent with
      the existing literature about compliance with PERS, that is wearing and using the
      device. Findings from this study suggested that PERS use is a reassuring
      presence, is simple and effortless, if you need it, and alone, but connected. The
      overarching theme is PERS is an adjunctive resource that it is a helpful backup
      and that promotes interconnectedness.

PMID- 30282140
TI  - Black Student Participation Rates Also a Concern for Educational Program
      Assessments.
AB  - Lower participation rates in the African-American population are not limited to
      medical research. Extant research reveals African-American students also
      participate at lower rates than other racial groups on college and university
      surveys. Students in medical and health professions programs are routinely
      surveyed to investigate students' perspectives about the educational curriculum,
      social and cultural environment, quality of faculty and resources, etc. The
      results attained from these assessments often carry some of the greatest weight
      in guiding educational curricula, programs, and policy. Thus, perhaps nowhere is
      there greater opportunity for African-American students to effect change than
      educational program assessments, where results will affect not only current and
      future students, but may also help improve professional development opportunities
      to address health disparities among minority populations. Implications and
      recommendations for faculty, administrators, and students in medical and health
      training programs are discussed.

PMID- 30282141
TI  - [Classification of sudden deafness prognosis based on deep learning method].
AB  - Objective:This study aimed to develop predictive models for sudden sensorineural
      hearing loss through deep belief network (DBN) and explore whether the model
      performances differ when adopting different outcome criteria. Method: 228
      potential predictors involving the clinical characteristics, audio logical data,
      and serological parameters out of 1 220 hospitalized SSHL patients who were
      admitted from June 2008 to December 2015 were analyzed retrospectively. The
      hearing data of sudden deafness were classified into two or four categories based
      on Chinese criteria and Siegel criteria, which were used to develop the DBN
      models. The area under the receiver operating characteristic curve (ROC-?AUC) and
      accuracy were used to compare the predictive performance of different models.
      Result: The DBN model developed for predicting the dichotomized outcomes had
      better performance than that of the four?category outcomes. When the iteration
      number reached 500 times, DBN model constructed for prediction of dichotomized
      outcomes based on Siegel's criteria had demonstrated the best performance with an
      accuracy of 76.25% and an AUC of 0.81. According to indices from first layer
      weights, DBN gave a rank of top 10 sensitive features for hearing outcome
      prediction focusing on indicators regarding coagulation, demographics and pre
      treatment hearing levels independent of the outcome assessment criteria.
      Conclusion: DBN provides a robust outcome prediction ability in SSHL datasets
      with rich and complex variables, especially when utilized to predict dichotomized
      outcomes based on the Siegel criteria. In addition, this advanced deep learning
      technique can automatically extract valuable predictors, which is consistent with
      those that had been verified in previous studies by traditional statistical
      methods. This study provides further evidence for extending the use of DBN
      algorithm to the field of developing prediction or classification models for
      other otological diseases in the future.?.

PMID- 30282142
TI  - [Clinical comparative study of caloric test with water or air in
      healthyindividuals and diagnosing study on air caloric test].
AB  - Objective:To explore the equivalence of the test results of the water or air
      caloric tests and the compliance of the test in the healthy individuals. To
      provide scientific basis for clinical standardization of caloric test.Method:
      Randomized crossover clinical trial, 60 healthy individuals were divided into
      group A and group B. Water caloric test was carried out first in group A, and air
      caloric test was carried out after elution effect(one day interval). The
      treatment of group B was opposite to group A. SPV(Slow Phase Velocity), CP(canal
      paralysis) and SPV and CP' s 95%CI were used as evaluation indexes to analyze the
      equivalence of water and air caloric test in healthy people and the clinical
      normal reference value and stability and compliance of the water and air caloric
      test. Result: 160 cases of caloric test CP value of chi square test suggested
      that there was no statistical difference between two kinds of media in the
      examination of the vestibular function of healthy individuals, and the CP value
      of the two was 85%(51/60). 2the SPV value of the was obviously higher than that
      of the air caloric test. The SPV value at each temperature of the water caloric
      test stimulation is quite different from the air caloric test stimulation. 3The
      range of water caloric test stimulation CP 95%CI was 8%-12%, and the average
      value was 10%. The interval of air caloric test stimulation CP 95%CI was 10%-15%
      and the average value was 12%. 4This study provided the corresponding SPV 95%CI
      as the medical reference values. 5The subjects of 98.33%(59/60) of the
      questionnaire survey selecting air caloric test and the results of the
      observation indicated that the duration of the air caloric test was shorter and
      more comfortable. Conclusion: 1Air caloric test can satisfied the needs of
      clinical assessment of horizontal semicircular canal function, and can make
      patients feel more comfortable. However, due to the weak intensity of nystagmus,
      water caloric test has to be used when the SPV value is too low. 2In this study,
      the upper limit of the CP value of the air caloric test in healthy individuals
      was 0.21, which is quite different from the upper limit of the standard value was
      0.25 of the water caloric test. Therefore, the laboratory should establish their
      own reference value of the laboratory caloric test, and should not blindly apply
      the standard value of the water caloric test as the standard of the hemiplegia of
      the unilateral semicircular canal. The results of this study suggest that air
      caloric test can be used instead of water caloric test in clinic. And if the
      patient has no contraindications, air caloric test can be used as a priority.

PMID- 30282143
TI  - [Study on the characteristics and clinical significance of relief of nystagmus
      during the restoration of benign paroxysmal positional vertigo with posterior
      semicircular canal].
AB  - Objective:The features and parameters of the relief of nystagmus during the
      restoration of benign paroxysmal positional vertigo(PC-BPPV) in the posterior
      semicircular canal were observed to explore its clinical significance and
      mechanism.Method: Sixty-eight patients with PC-BPPV were treated with the Epley
      method. According to the subject' nystagmus relief was present or not, they were
      divided into two groups: group A showed relief of nystagmus during the
      restoration process, and group B showed no relief of nystagmus during the
      restoration. The effect of restoration between group A and group B was compared,
      and the parameters of nystagmus between the detached nystagmus and the Hallpike
      position in group A patients with detachable nystagmus were compared. Result: Of
      the 68 patients with PC-BPPV, 33(48.5%) experienced detachment of nystagmus in
      the same direction as the initial nystagmus(Group A) during the restoration;
      35(51.5%) patients had no nystagmus during the restoration(Group B). After the
      instrument was reset for 2 h, Dix-Hallpike test was performed again. The success
      rate of reset was 100% in group A,and that was 57% in group B(20 cases were
      successfully repositioned, and 15 cases showed typical nystagmus). The success
      rate of reset was statistically different between groups A and B(P<0.01). After
      one week of resetting, the telephone follow-up was carried out. The recovery rate
      of group A and group B were 93% and 74% separately.The recovery rates between
      group A and B were statistically different(P<0.05). In group A, the nystagmus
      latency at Hallpike was(2.63+/-2.17) s, and the duration was(17.27+/-5.94) s. The
      rate of nystagmus in the upper leaping eye was(16.19+/-9.54) degrees /s. The
      latency of liberation was(2.30+/-1.41) s and the duration was(11.84+/-5.98) s. In
      seconds, the slow phase phasic velocity of the nystagmus was(7.80+/-4.57) degrees
      /s; there was no statistical difference in latency between the detached nystagmus
      and the Hallpike nystagmus(P>0.05), while there was a statistically significant
      difference between the duration and the nystagmus
      intensity(P<0.01).Conclusion:For PC-BPPV restoration, the presence or absence of
      nystagmus can be used as a reference to judge whether the restoration succeed or
      not.The latency of nystagmus at the Hallpike position may be related to the
      stalactite precipitation rate. The duration and the slow phase angle velocity of
      the upper hop eye may be related to the otolith quantity.

PMID- 30282144
TI  - [Therapeutic effects of postauricularinjection of lidocaine in tinnitus].
AB  - : Objective:To observe clinical efficacy of postauricular injection of lidocaine
      for subjective tinnitus and explore the clinical effective method in the
      treatment of tinnitus. METHOD: Eighty patients with tinnitus as their first
      complaint were included in our study. They were randomly divided into four
      groups, each with 20 cases.They were treated with oral ginaton and mecobalamin
      tablets,and at the same time with postauricular injection of lidocaine at
      different doses (Group A, 2% lidocaine 3 ml; Group B, 2% lidocaine 2
      ml+physiological saline 1 ml;Group C, 2% lidocaine 1 ml+physiological saline 2
      ml; Group D, physiological saline 3 ml). TEQ scores were evaluated and compared
      before treatment, at the end of treatment, and one month after
      treatment.Result:At the end of treatment, the clinical effiCIency rates of four
      groups were 80%,70%,65% and 25% respectively. One month after treatment, the
      clinical effiCIency rates of four groups were 80%, 55%, 45% and 0% respectively.
      There were significant differences among four groups by chi square test
      (P<0.05).Patients' TEQ scores of the four groups after treatment were analyzed
      and compared by one-way ANOVA. TEQ scores of Group A,B and C were lower than
      Group D(P<0.05). TEQ scores of Group A were lower than Group C(P<0.05).TEQ scores
      at the end of treatment and one month after treatment were analyzed by paired t
      test. Group B and C had higher TEQ scores one month after treatment(P<0.05).The
      total effective rate at the end of treatment for acute, subacute and chronic
      tinnitus patients was 79.31%, 70.83% and 42.86% respectively. The total effective
      rate of one month after treatment was 75.86%, 45.83% and 42.86%, respectively.
      The results of chi square test showed that the total effective rate of acute
      tinnitus patients was significantly higher than that of subacute and chronic
      tinnitus in one month after treatment (P<0.05). CONCLUSION: Postauricular
      injection of lidocaine is effective for simple subjective tinnitus, and the dose
      and concentration of lidocaine affect the efficacy and durability. Postauricular
      injection of lidocaine for the treatment of subjective tinnitus is a therapeutic
      method worthy of further research and popularization.

PMID- 30282145
TI  - [Progress in research of vestibular migraine].
AB  - Estibular migraineis a common disease with symptoms of vertigo and migraine,which
      is the most common type of recurrent vertigo. The overall prevalence rate of the
      population is up to 1%. However, owing to its diversity of symptoms, large
      individual differences, the scarcity of professional clinical knowledge and the
      lack of effective diagnostic means, the rate of misdiagnosis is very high.
      Therefore, this article summarized the parts of clinical manifestations,
      pathogenesis, diagnostic criteria, treatment and prevention of vestibular
      migraine.

PMID- 30282146
TI  - [Progress in diagnosis and treatment of unilateralsensorineural hearing loss in
      children].
AB  - Unilateral sensorineural hearing loss (USNHL) in children have traditionally been
      underappreciated, so we reviewed the recent researches about USNHL in children to
      understand their effect on development and the underlying pathophysiologic
      mechanisms. Early diagnosis and treatment of USNHL have a positive effect on
      verbal cognitive, linguistic, communicative, and socio-emotional development, as
      demonstrated by neurophysiological studies. And the audiological management of
      hearing loss should be placed within a comprehensive rehabilitative approach.
      Among the treatment modalities with differing effects on the quality of binaural
      hearing, cochlear implants are now used increasingly in children with severe-to
      profound USNHL. But the long-term effect and indication selection still need
      further study.

PMID- 30282147
TI  - [Demographic characteristics and canalith repositioning efficacy in 907 patients
      with typical benign paroxysmal positional vertigo].
AB  - AbstractObjective:To review the demographic characteristics and canalith
      repositioning efficacy in 907 patients with typical benign paroxysmal positional
      vertigo(BPPV). Method: The demographic characteristics of 907 patients with
      typical BPPV were statistically analyzed. According to the type of BPPV, patients
      were treated with the appropriate repositioning maneuver, and the clinical
      efficacy of repositioning maneuver was analyzed and summarized. Result: Nine
      hundred and seven patients of BPPV with typical nystagmus were elected in this
      study. 585 out of 907 were female and 322 out of were male, and the mean age was
      53.10+/-14.25(13 to 89) years. The lesion located to the posterior semiCIrcular
      canal was 489 patients(53.9%), horizontal semiCIrcular canal was 312
      patients(34.4%), anterior semiCIrcular was 63 patients(6.9%), and multiple
      semiCIrcular was 43 patients(4.8%). According to Kaplan-Meier survival analysis
      curve, the median cure time for the modified Semont and Epley repositioning
      maneuver in PC-BPPV groups was 3 days, and there was no significant difference in
      survival curves between the two repositioning maneuver. Meanwhile, the median
      cure time for Barbecue and Li horizontal canal quick repositioning maneuver
      groups was 3 days, and 1 day for Gufoni repositioning maneuver group in HC-BPPV
      groups. And there was no significant difference in survival curves among the
      three repositioning maneuver. In the AC-BPPV, 7 cases, 31 cases, 57 cases, 58
      cases were cured with the Li anterior canal quick repositioning maneuver in the
      1st day, the 3rd day, 1 week later, and 1 month later, and 5 cases lost to be
      follow-up. According to Kaplan-Meier survival analysis curve, the median cure
      time for the Li anterior canal quick repositioning maneuver in AC-BPPV groups was
      3 days. Conclusion:Repositioning maneuver represents a simple, safe, rapid and
      effective approach to the treatment of BPPV. Therefore, repositioning maneuver
      should be choice for the BPPV treatment.

PMID- 30282148
TI  - [Analysis of neurobehavioral function of school-aged children with sleep
      disordered breathing].
AB  - Objective: To investigate the neurobehavioral function(attention, executive
      skills, behavior) of school-aged with varying degrees of SDB and control children
      with no history of SDB recruited from the community.Method: One hundred and sixty
      three children aged from 7 to 12 were enrolled in the study. Children were
      devided into 4 groups through the data of Routine overnight polysomnography(PSG):
      PS(n=71) group, mild OSAHS (n=29) group, moderate/severe OSAHS(n=21) group, and
      controls(n=42) group. The Behavior Rating Inventory of Executive Function(BRIEF)
      and the Child Behavior Checklist(CBCL) were used to assess attention, executive
      function and behavioral function. Result: There was significant difference of
      AHI, OAI, RAI, SAI and SpO 2 nadir between the mild/MS groups and the control/PS
      groups(F=1174.3, 1178.0, 2348.3, 34.7, 377.7, P<0.05). Total sleep time(TST) of
      the MS OSAHS group was significantly less than that in the control group(F=178.8,
      P<0.05). Increased rates of behavioral executive dysfunction were found depending
      on the SDB spectrum(F=181.2, 274.2, 284.5, P<0.05). Children with all severities
      of SDB had signicantly higher rates of total, internalizing and externalizing
      behavioral problems compared to control group(F=361.7, 168.3, 564.0, P<0.05).
      Conclusion:Our study suggests that behavioral, attention, and executive function
      difficulties are present in children with PS as well as OSAHS. These results have
      implications for the treatment of milder forms of SDB, particularly PS, which is
      commonly viewed as benign.

PMID- 30282149
TI  - [Rapeutic effect analysis of the auricle appliance on 2-6 months old infants with
      congenital auricle deformity].
AB  - Objective: To study the effect of amazing ear correction system on 2-6 months old
      infants with congenital ear deformity. Method: Thirty infants (37 ears) with
      congenital auricular deformities were enrolled in the study. Deformities included
      constriction, cryptopia, helicalrim, prominent, conchal strut, and Stahl
      deformities and microtia. The patients were divided into 2 groups. Infants elder
      than 2 months were 20 cases(26 auricular malformed ears). And infants under 2
      months old were 10 cases(11 auricular malformed ears). All the patients underwent
      ear molding using the amazing ears correction system. The patients of each group
      were followed-up for at least 3 months. Result: The results were divided into
      three levels(excellent, good, and poor) according to the correction of auricular
      shape. In Group elder than 2 months, 13 ears were excellent and the average
      treatment time was 46.85 days,5 ears were good, the average treatment time was
      43.40 days and 8 ears were poor, the average treatment time was 13.13 days. In
      Group under 2 months old, 5 ears were excellent and the average treatment time
      was 28.80 days,6 ears were good and the average treatment time was 18.66 days.
      The patients of each group were followed-up for at least 3 months and no rebound
      occurred. Conclusion:Ear correction system has a significant effect on those more
      than 2 months and less than 6 months with congenital auricular deformity. The
      children who were more than 2 months old need to wear the auricle appliance over
      6 weeks to achieve a satisfactory effect.

PMID- 30282150
TI  - [Correlation between laryngopharyngeal reflux and otitis media with effusion in
      adults patients].
AB  - Objective:Using the pepsin A concentration to investigate the relationship among
      gastroesophageal Reflux/laryngopharyngeal reflux and otitis media with effusion
      in adults patients.Method: Adults with OME underwent myringotomy with tube
      placement or eardrum puncturing suction were collected in the study group and the
      patients with coclear implatation were collected as control group. A standard
      sandwich Enzyme-linked Immunosorbent Assay (ELISA) method was applied to measure
      pepsin A concentration in the middle ear fluid.RSI and GERD-Q were used for the
      patients in study group.Result: Pepsin A concentration was (23.72+/-26.64; 2.00
      84.47 ng/ml) in study group.The positive rates of pepsin A in the patients and
      samples were 21.69%(18/83) and 17.27%(19/110) respectively.In the control group,
      no pepsin A was detected in 26 samples. In the study group, 5 (6.02%) were
      diagnozid with GERD and 19 out of 83 patients (22.89%,19/83) were diagnosed with
      LPRD.LPRD, 8 out of 18 patients (44.44%) in the pepsin A positive group, was much
      higher than that in the pepsin A negative group (16.92%)(P<0.01).Conclusion:
      Laryngopharyngeal reflux was an important pathogeny of OME in adults patients,
      although those patients maybe have no any symptoms of GERD. The fat maybe be one
      of a indirect risk factor of OME in adults.

PMID- 30282151
TI  - [The clinical efficacy of vidian neurectomy and conservative treatment on
      moderate-severe allergic rhinitis: a Meta-analysis].
AB  - Objective: To compare the clinical effects of vidian neurectomy with conservative
      management in the treatment for moderate-severe allergic rhinitis. Method: The
      studies using case controlled trials which were retrieved from Embase, Pubmed,
      Web of Science, Cochrane Library etc. The Cochrane risk assessment criteria were
      used to evaluate the quality of the articles that met the inclusion criteria.
      Manager 5.3 software was used to data analysis. Result: Six articles were
      included in meta-analysis. Meta-analysis showed that vidian neurectomy group got
      lower RQLQ scores[95%CI (-0.98,-0.63),P<0.001], less inCIdence of
      complications[95%CI (0.17, 0.67), P=0.002], lower VAS score[95%CI (-3.97,-3.65),
      P<0.001]and higher clinically effective ratio[95%CI (1.18, 50.52), P=0.03]than
      conservative treatment group. Conclusion:In summary, we believe that nasal
      endoscopic vidian neurectomy in the treatment of moderate-severe allergic
      rhinitis is superior to conservative treatment.

PMID- 30282152
TI  - [Screening of hot-spot deafness gene mutations among 277 cochlear implantation
      patients in Sichuan province].
AB  - Objective:To investigate the spectrum and incidence of the hot-spot deafness gene
      mutations of 277 patients with cochlear implantation in Sichuan province, and to
      provide information of the prevention and treatment for clinical application.
      Method: The data of the hotspot deafness gene mutations screening of 277 patients
      with cochlear implantation was analyzed retrospectively. A deafness related gene
      mutations detection kit was used to detect 9 mutation sites in four deafness
      associated genes,including GJB2(35delG,176del16,235delC,299delAT),
      GJB3(538C>T),SLC26A4(2168A>G, IVS7-2A>G), Mitochondrial 12SrRNA(1494C>T,
      1555A>G). Result: 1 A total of 122 patients with hot-spot Deafness Gene Mutations
      were detected in 277 cochlear implantation patients(44.04%),among which there
      were 39 patients were GJB2235delC homozygous mutation(14.08%), 23 patients were
      GJB2 235delC heterozygous mutation(8.30%), 1 patient was GJB2 299delAT homozygous
      mutation(0.36%), 2 patients were GJB2 176del16& 235delC compound heterozygous
      mutation(0.72%), 13 patients were GJB2 235delC& 299delAT compound heterozygous
      mutation(4.69%), 2 patients were SLC26A4 2168A>G heterozygous mutation(0.72%), 16
      patients were SLC26A4 IVS7-2A>G homozygous mutation(5.78%), 22 patient were
      SLC26A4 IVS7-2A>G heterozygous mutation(7.94%), 1 patients was SLC26A4 2168A>G&
      IVS7-2A>G compound heterozygous mutation(0.36%), 2 patients were mitochondrial
      12SrRNA gene 1555A>G homogenous mutation(0.72%), 1 patient carried both GJB2
      235delC homozygous mutation and SLC26A4 IVS7-2A>G heterozygous mutation(0.36%).
      2A total of 49 patients with LVAS were found in 277 cochlear implantation
      patients: including 15 patients with IVS7-2A>G homozygous mutation(30.61%), 22
      patients with IVS7-2A>G heterozygous mutation(44.90%), 1 patient with 2168A>G
      heterozygous mutation(2.04%), 1 patient with complex heterozygosis mutations of
      2168A>G and IVS7-2A>G(2.04%), 1 patient with GJB2 235delC homozygous
      mutation(2.04%) and 1 patient with GJB2 235delC&299delAT compound heterozygous
      mutation(2.04%), and no hotspot deafness gene mutations were found in 8 patients.
      3There were 40 out of 277 cochlear implantation patients with definite family
      history.There was no statistic difference of the detection rate of hot-spot
      deafness gene mutations between in patients with family deafness history (57.50%)
      and in patients without family deafness history (41.77%). 4A total of 273
      patients with profound binaural deafness were found among 277 cochlear
      implantation patients. Three patients with profound deafness in right ear and
      severe deafness in left ear were found among 277 cochlear implantation
      patients.Two patients of three were SLC26A4 IVS7-2A>G heterozygosis mutations,
      and one patient of three was GJB2 235delC heterozygosis mutations; 1 patient with
      profound deafness in left ear and severe deafness in right ear was found among
      277 cochlear implantation patients,and was GJB2 235delC heterozygosis mutations.
      Conclusion:1 The detection rate of hotspot deafness gene mutations in 277
      cochlear implantation patients is 44.04%(122/277). GJB2 Mutation is the most
      common, SLC26A4 mutation takes the second place, mitochondrial 12SrRNAgene
      mutation is not common and GJB3 mutation is not found in this study.2 SLC26A4
      mutation may not be the sole pathogenic factor of LVAS. 3 The results of this
      study suggest that the genetic background of cochlear implants patients has
      little effect on the data of the hotspot deafness gene mutations screening.

PMID- 30282153
TI  - [The study of life quality in children with obstructive sleep apnea].
AB  - AbstractObjective:To study the effect of obstructive sleep apnea(OSA) on the life
      quality of children. Method: Forty-four OSA children diagnosed with overnight
      polysomnography were selected as the research object, 35 cases of pediatric no
      snoring healthy children were as control. The inventory of subjective life
      quality and children's self-rating anxiety scale were used to assess children' s
      life quality. Result: Depending on the data of the inventory of subjective life
      quality questionnaire, each level and dimension of children' s life quality
      satisfaction scores in OSA group were significantly lower than that in healthy
      controls(P<0.05), especially in the cognitive component of school life(3.78+/
      1.73) and the affective component of depression experience(3.70+/-2.18). The
      score of anxiety disorder in OSA group (21.39+/-10.49) was higher than that in
      healthy control group(14.21+/-9.69)( P<0.05). The rate of anxiety disorder in OSA
      group was higher than that in healthy control group(P<0.05). Conclusion:Children
      in OSA group had higher incidence of unsatisfactory life quality in all levels
      and dimensions. OSA group children dissatisfied with the life quality in each
      level, each dimensions have significant statistical difference, especially in the
      cognitive component of school life and affective components of depression
      experience. The OSA group had higher anxiety disorders than healthy ones.

PMID- 30282154
TI  - [Risk factors analysis for recurrence of the idiopathic benign paroxysmal
      positional vertigo].
AB  - Objective:To study the risk factors of recurrence in patients with benign
      paroxysmal positional vertigo(BPPV) after successful repositioning treatment.
      Method: Two hundred and two cases of confirmed BPPV patients, were followed-up
      for 10 months after particle repositioning, and the incidence of recurrence was
      analyzed. The risk factors for recurrence were analyzed by logistic regression.
      Result: 51 out of 202 confirmed BPPV patients complained of recurrence. There was
      significant difference of the duration of vertigo before treatment, the times of
      repositioning and SDS between the two group(P<0.05). While the sex, the age, the
      incubation period of BPPV, the duration time of BPPV, underlying diseases and the
      type of canal were not associated with the residual dizziness(P>0.05). Logistic
      regression analysis showed that the times of repositioning and the SDS were the
      risk factor for residual dizziness. Conclusion:The effective repositioning and
      the psychological care are very important to reduce the recurrence of BPPV.

PMID- 30282155
TI  - [Retrospective analysis of 273 benign fibro osseous lesionsin the sinus and
      maxillofacial region].
AB  - Objective:To compare and analyze the incidence, clinical features ,imaging
      features, the preoperative serum alkalinosis phosphatase (ALP) and recurrence
      rates of osteoma, ossifying fibroma (OF), and fibrous dysplasia (FD) in sinus and
      maxillofacial benign fibrosis (FOLS). Method: The 273 cases of FOLS with
      paranasal sinus and maxillofacial region in our hospital, among which there were
      153 cases of osteoma, 44 cases of OF, and 76 cases of FD, were reviewed
      retrospectively and were follow-up for 6 months to 5 years. The incidence,
      gender, age, lesion location, preoperative serum ALP levels and recurrence rate
      of different lesions were analyzed and compared. Result:Most Osteoma occurred in
      paranasal sinus (72.5%),among which the most common part was ethmoid sinus
      (50.3%) and followed by the frontal sinus (22.1%),the ratio of female to male was
      2:1,and there were 27 cases (17.7%) accompanied by sinusitis.None of the patients
      relapsed. Most OF occurred in the maxillofaCIal bone (65.9%) and most of the
      lesions were monostotic (75.0%).For those occurred in the paranasal sinuses,the
      ethmoid sinus (27.3%)were the most common part than others. The ratio of femal to
      male was almost 1?1 and there were 12 cases (27.3%) accompanied by sinusitis. The
      recurrence rate of the OF was 13.6%.Most FD occured in maxillofacial bone (64.5%)
      were the monostotic form(64.5%) ,and in which the most common part was the
      maxilla (50.0%). While,most of those occurred in the paranasal sinuses were the
      polyostotic ones,and sphenoid sinus (34.2%) were the most common parts.The ratio
      of femal to male was almost 1?1 and there were 10 cases (13.2%) accompanied by
      sinusitis. 12 cases relapsed (14.5%),and there were 9 cases (75.0%) acceptted the
      first surgery before the age of 20.The average age of onset among Osteoma[(40.7+/
      14.55)y],OF[(28.0+/-17.9)y] and FD[(20.32+/-15.2)y] were significant different
      (P<0.01).The preoperative serum ALP content among Osteoma[(68.3+/-24.1)U/L,
      OF(130.1+/-107.0) U/L and FD were (127.7+/-78.7) U/L significant
      different(P<0.01).Nevertheless,there were no differences of the preoperative
      serum ALP content between the monostotic and polyostotic in OF cases[(117.2+/
      92.6) U/L,(168.7+/-140.1) U/L respectively,( P>0.01)],as well as that between FD
      cases[(122.2+/-82.9) U/L, (137.7+/-70.7) U/L (P>0.01)]. Conclusion:The
      differences of the inCIdence,the age of onset,leision location,preoperative serum
      ALP content and reccurence rate among Osteoma,OF and FD are statistically
      significant.Surgery is the most effective treatment at present.

PMID- 30282156
TI  - [One case report of laryngeal large cell neuroendocrine carcioma].
AB  - The clinical data of large cell neuroendcrine carcinoma were analyzed
      retrospectively.The patient was a middle-age male,complained of throat pain for
      10 years, it was misdiagnosed as chronic pharyngitis. The patient received
      tracheotomy, vertical laryngeal resection and left cervical lymph node
      dissection. Half month after surgery, the patient was transferred to the oncology
      department and remains under follow-up. Large cell neuroendcrine carcinoma is a
      rare malignant tumor, which is easily misdiagnosed. To Mastering its clinical
      features is important for the diagnosis and treatment.

PMID- 30282157
TI  - [A case of extramedullary plasmacytoma of the nasal cavity].
AB  - A case of extramedullary plasmacytoma of the nasal cavity was reported and its
      mainly clinical manifestations were nasal obstruction, running nose and olfactory
      degeneration. Nasal endoscopy and paranasal sinus CT indicated tract tumor in
      left nasal (the nature to be investigated), the pathological result after
      surgical resection of the tumor suggests extramedullaryplasmacytoma (left nasal
      cavity).Clinical diagnosis was extramedullaryplasmacytoma (left nasal cavity),
      chronic sinusitis (left). Radiotherapy was continued after discharge and the
      follow-up was satisfactory.

PMID- 30282158
TI  - [Primary laryngeal Non-Hodgkin' s lymphoma: a case report].
AB  - Non-Hodgkin' s lymphoma is a kind of disease which might manifest in varied form.
      Unlike squamous cell carcinoma, the majority of laryngeal tumors, non-Hodgkin' s
      lymphoma in larynx is extremely rare. Here we present a primary laryngeal non
      Hodgkin' s lymphoma, a 66-year-old female, with a history of recurrent sore
      throat and hoarseness for over 1 year. Laryngoscope and computed tomography
      result were presented, and surgical resection was performed under the suspension
      laryngoscope using CO2 laser. According to the pathological immunohistochemistry
      result, the final diagnosis was laryngeal non-Hodgkin' s lymphoma. Postoperative
      adjuvant chemotherapy was applied. There was no recurrence.

PMID- 30282159
TI  - [Research progress of microRNA as a biomarkerof papillary thyroid carcinoma].
AB  - Thyroid cancer is a common malignancy derived from the endocrine system and the
      incidence of thyroid cancer is on the rise. Papillary thyroid carcinoma (PTC) is
      the most common type, and 90% of PTC patients have long-term survival, but the
      recurrence rate is still as high as 30%. Current diagnostic and postoperative
      monitoring techniques have been developed, but their negative rates and
      interfering factors also occupy an absolute proportion, and lack specific markers
      for the prognosis of PTC. Studies have shown that microRNAs (miRNAs) are
      associated with the development, metastasis and invasiveness of PTC and as a
      biomarker to aid in the diagnosis and monitoring of recurrence, and to determine
      the prognosis for specific markers. The future of PTC diagnosis, treatment and
      improve prognosis has broad prospects. This review mainly describes the
      development of miRNA as biomarkers for the diagnosis, recurrence and prognosis of
      PTC.

PMID- 30282160
TI  - [Diagnosis and treatment of eosinophilic rhinosinusitis].
AB  - Chronic rhinosinusitis (CRS), a chronic inflammation of the nasal sinus mucosa,
      is based on a simplified classification of a single clinical phenotype (with or
      without nasal polyps) that does not adequately reflect the heterogeneity of the
      pathogenesis of chronic rhinosinusitis complexity. Currently, according to the
      lesion mucosa or polyps eosinophil infiltration,this type of chronic rhinosinusit
      is known as eosinophilic chronic rhinosinusitis (ECRS). The curative effect of
      ECRS is poor than non-eosinophilic rhinosinusitis. This article summarizing the
      diagnosis and treatment of eosinophilic rhinosinusitis status, is to provide help
      for clinical diagnosis and treatment.

PMID- 30282161
TI  - [Precision diagnosis and treatment for Treacher Collins syndrome:preclinical
      perspectives].

PMID- 30282162
TI  - [Precision diagnosis and treatment for Treacher Collins syndrome:clinical
      perspectives].

PMID- 30282163
TI  - [Dominant deafness and onychodystrophy syndrome].

PMID- 30282164
TI  - [Dominant deafness and onychodystrophy syndrome].

PMID- 30282165
TI  - [Emphasizing the application of genetic diagnosis in branchio-oto-renal
      syndrome].
AB  - Summary Branchio-oto-renal syndrome (BOR) is an autosomal dominant genetic
      disorder characterized by branchial fistulas, hearing impairment, renal
      malformations and auricular anomalies. Pathogenic mutations have been discovered
      in several genes such as EYA1, SIX5, and SIX1. However, it has a high penetrance
      with variable expressivity. The clinical and genetical heterogeneity is
      widespread amongst and within families. In this review, we describe the clinical
      manifestations and pathogenic genes with copy number variations in detail, and
      emphasize the criteria clinically and genetically to provide the basis for
      clinical diagnosis of BOR and genetic counseling.

PMID- 30282166
TI  - [X-linked Alport syndrome: auditory pathogenic variant features and further
      genotype-phenotype correlations in female patients].
AB  - Objective:To analyze the audiological characteristics of female patients with X
      linked Alport syndrome and to explore the relationship between genotype and
      phenotype in China. Method:The hearing data of 64 females diagnosed as Alport
      syndrome was reviewed and analyzed. All coding exons of COL4A5 genes were PCR
      amplified and sequenced with genomic DNA, or mRNA of COL4A5 gene was RT-PCR
      amplified and sequenced with skin fibroblast. Result:The 64 cases who were
      accompanied by hematuria or proteinuria all received pure tone audiometry and
      acoustic immitance test. The incidence of hearing loss was 20.31% (13/64). The
      hearing were bilaterally symmetrical sensorineural deafness, most of which were
      mild and moderate hearing loss. The hearing curve is the groove curve. Among the
      64 patients, 42 kinds of DNA variants were detected in 52 cases. Among the
      patients with hearing loss, 1 of them was 12 years old and the rest were over 35
      years old. Mild mutations in 13 cases (10 cases of normal hearing and 3 cases of
      mild hearing loss) and severe mutations in in 12 cases ( 6 cases of normal
      hearing and 6 cases of mild to moderate hearing loss) were found in 25 cases over
      35 years old. A total of 26 cases were followed up for 2 years or more, of which
      7 cases had a downward trend of hearing loss, decreased about 5 dB each year, and
      there was no significant change in the hearing of the other patients.
      Conclusion:Mild and moderate hearing impairment, and groove type of audiometric
      curve are mainly found in Chinese X-linked Alport syndrome in females. Hearing
      loss occurs at middle-age. The onset time of hearing loss was later than that of
      the male, and the severity of hearing loss was lighter than that of the male. In
      the course of follow-up, some patients had a downward trend in hearing, and there
      was no significant correlation between the hearing phenotype and the genotype.

PMID- 30282167
TI  - [Cochlear implantation and early outcomes in children with incompletely partition
      type III malformation].
AB  - Objective:To analyze the early effect of the cochlear implantation (CI) in
      children with cochlear incompletely partition type III malformation (IP-III).
      Method:Ten children with IP-III malformation who underwent CI were recruited in
      this study. The hearing characteristics, preoperative speech performance and
      surgery were analyzed retrospectively. The aided hearing threshold with CI, the
      categories of auditory performance (CAP) score, speech intelligibility rating
      (SIR) score and speech perception were designed to access the benefits of CI. Ten
      children with normal cochlea were also enrolled as the control group. Demographic
      information of children in the control group including hearing loss and speech
      level before implantation, age at implantation, hearing aids using history,
      duration with CI were matched with those in the IP-III group. The hearing
      threshold, CAP score and SIR score in the IP-III group were compared with the
      control group using the SPSS 20.0 software. Result:The computed tomography of
      temporal bones showed typical IP-III malformation in all patients. The electrode
      arrays were properly and totally implanted in all children. Cerebrospinal fluid
      gusher occurred intra-operatively, and no other complications in all patients.
      The pure tone average (PTA) threshold at the 3rd, 6th, 9th and 12th month after
      implantation were (40.8+/-8.5) dB HL, (36.1+/-9.1) dB HL, (32.5+/-6.8) dB HL and
      (33.0+/-7.3) dB HL, respectively. The PTA thresholds in the IP-III group were
      similar to those in the control group at all tested time points (P>0.05). At the
      3rd, 6th, 9th and 12th month after implantation, the CAP scores in the IP-III
      group were lower than those in the control group, but there was no significantly
      difference (P>0.05). Furthermore, the SIR scores were lower than those in the
      control group, and there were significantly difference at the 6 th, 9 th and 12
      th month after implantation (P<0.05). Conclusion:CI was an effective treatment
      for children with IP-III malformation. Surgery on IP-III was challenging,
      however, seldom complication would occur with excellent surgical skills. Though
      the CI was benefit for IP-III, the development of hearing and speech ability were
      slower than children with normal cochlea.

PMID- 30282168
TI  - [Goldenhar syndrome].
AB  - Summary Goldenhar syndrome is a condition characterized by alterations involving
      the development of the structures of the first and second branchial arches. The
      abnormalities primarily affect the face, the eyes, the spine, and the ears, and
      the auricular abnormalities are associated with possible hearing loss. Here, we
      present a review of the literature on Goldenhar syndrome, discussing what is
      known about the clinical phenotype , the aetiology, audiological findings and
      treatment,in order to provide certain help for people about disease diagnosis,
      genetic counseling and hearing intervention.

PMID- 30282169
TI  - [Application of surgical cricothyrotomy in emergency and complicated airway
      management].
AB  - Objective:To explore the feasibility of intercricothyrotomy in emergency airway
      management. Method:Characteristics of 27 cases underwent surgical cricothyrotomy
      were analyzed. Result:The main causes of emergency were severe trauma of head and
      neck, larynx stenosis, interspaces infection of the floor of the mouth and
      submaxillary space, etc; all the patients were divided into 2 groups : surgical
      cricothyrotomy as the first choice (group A,16/27) and surgical cricothyrotomy
      after conventional tracheotomy (group B,11/27); The average time of opening
      airway for group A was much shorter than group B [(58.12+/-24.41)s, (739.09+/
      245.29)s,respectively, P<0.01)]; Bleeding in group A (14 cases) was much less
      than group B (13 cases) [(2.36+/-1.16)ml, (4.65+/-4.31)ml,respectively, P<0.01];
      Except 1 cases died from primary disease, 4 cases with laryngeal stenosis
      underwent laryngeal dilation with T type expansion tube and 2 cases of bilateral
      recurrent laryngeal nerve palsy, the average time with tracheal tube of the
      remaining 20 patients was (12.35+/-7.29)d, no postoperative complications such as
      larynx or tracheal stenosis were found. All of them were successfully extubation.
      Conclusion:Surgical cricothyrotomy procedure is fast and safe with simple and
      convenient that can be used as the preferred method of rapid airway opening when
      a critical respiratory tract was difficult to manage.

PMID- 30282170
TI  - [The study of detection and etiology of unilateral deafness in children].
AB  - Objective:To explore the detection approach and aetiology of single-side
      deafness(SSD) in children and provide evidence for diagnoses and treatment.
      Method:A retrospective study was performed. Medical history and radiological data
      of children with unilateral deafness were analyzed. Result:The mean age at
      diagnosis was 6 years old. The mean age at diagnosis was 7.7 month because of
      failure of universal newborn hearing screening. Inner ear malformations were
      identified in 80.6% of cases. Cochlear nerve deficiency(CND) was observed in
      almost 77.8% of our cases, accounts for 96.6% in children with inner ear
      malformations. Conclusion:The children with SSD could be early detected by UNHS.
      CND is the main aetiology for SSD. MRI should be the first image choice when SSD
      children was diagnosed.

PMID- 30282171
TI  - [The application of modified cosmetic incision and skin adhesive in parotid
      benign tumor functional surgery].
AB  - Objective:To investigate the clinical application value and related technology of
      modified cosmetic incision and cyanoacrylate octyl ester skin adhesive
      (Dermabond) in functional surgery of parotid benign tumor. Method:Forty-two cases
      of clinical cases were collected and randomly divided into groups of A and B.
      Group A used the approach of modified cosmetic incision,intradermal suture with 6
      0 absorbable Vicryl stitches and gluing the skin with Dermabond. Group B used the
      approach of traditional S shaped incision and continuous suture of skin with 4-0
      Prolene stitches.The operative time, postoperative drainage volume, facial nerve
      function, salivary leakage, Frey syndrome, postoperative numbness, scar and
      aesthetic satisfaction were compared between the two groups. Result:The operation
      time, facial nerve function,Frey syndrome, salivary fistula, facial deformity and
      tumor recurrence in the two groups had no significant difference (P>0.05); but
      for postoperative drainage, postoperative numbness, facial appearance
      satisfaction, scar assessment, Group A was lower than Group B and there was
      statistical significance difference (P<0.05). Conclusion:The application of
      modified cosmetic incision and Dermond is safe and feasible. Its complication is
      lower than the traditional operation. The scar is smaller and more hidden, and
      the patient's satisfaction is higher. It doesn't affect the daily social
      interaction of patients, and achieves the effect of minimally invasive treatment.

PMID- 30282172
TI  - [Association between the morphological classification and prognosis of
      conservative treatment for vocal fold leukoplakia].
AB  - Objective:To explore the association between the morphological classification and
      prognosis of conservative treatment for vocal fold leukoplakia. Method:Patients
      with different types of vocal fold leukoplakia received conservative treatment
      first. Those who had failed response to conservative treatment or recurred
      received carbon dioxide laser resection. Then the efficacy and recurrence rate
      were compared among the three types of vocal fold leukoplakia. Result:Two hundred
      and thirty-six patients consisted of 78 flat and smooth cases, 146 bulge and
      smooth cases, and 12 rough cases. The complete response rate of conservative
      treatment for the three types was 80.8%, 65.1%, and 0%, respectively (P<0.01).
      Out of 158 patients who had complete response to conservative treatment, 10.1%
      cases recurred in 1 year (flat and smooth vs. bulge and smooth, 6.3% vs.
      12.6%,P=0.283). Totally, 78 patients had no complete response to conservative
      treatment and 16 patients experienced recurrence, whose complete response rate of
      carbon dioxide resection was 89.5%, 85.7%, and 75.0%, respectively (P=0.53). The
      pathological results were significantly different among three types. The complete
      response rate of conservative treatment combined with surgery for three types was
      97.4%, 93.8%, and 75.0%, respectively, and the complete response rate of flat and
      smooth type was significantly higher than that of rough type (P=0.002).
      Conclusion:The Conservative treatment could be based on the morphological
      classification of vocal fold leukoplakia. The treatment modality that
      conservative treatment combined with surgery had no impact on the prognosis of
      vocal fold leukoplakia.

PMID- 30282173
TI  - [Vestibular-evoked myogenic potentials in healthy guinea pigs].
AB  - Objective:To establish detection methods of air-conducted sound elicited
      vestibular-evoked myogenic potentials (ACS-VEMPs) in guinea pigs, including
      cervical vstibular-evoked myogenic potential (cVEMP) and ocular vestibular evoked
      myogenic potential (oVEMP). Method:Eleven healthy (250-350 g) guinea pigs (22
      ears) were selected and underwent conventional ACS-cVEMP and ACS-oVEMP
      examinations. Parameters of waveforms were recorded. Result:The ACS-cVEMP and ACS
      oVEMP could be elicited in 77.27% and 59.09% guinea pigs,respectively;threshold
      was (107.1+/-14.6)dB SPL and (115.5+/-15.6)dB SPL for ACS-cVEMP and ACS
      oVEMP;n1,p1 latency for cVEMP was (7.4+/-1.5)ms and (9.3+/-1.6)ms,(6.4+/-1.4)ms
      and (8.1+/-1.8)ms for oVEMP;amlipude was (15.4+/-8.6)MUV and (11.4+/-6.0)MUV for
      cVEMP and oVEMP respectively. No statistical difference could be found in above
      parameters between ACS-cVEMP and ACS-oVEMP (P>0.05). Conclusion:Both ACS-cVEMP
      and ACS-oVEMP could be elicited in guinea pigs.

PMID- 30282174
TI  - [Outcomes of same-day bilateral endoscopic tympanoplasty].
AB  - Objective:To investigate the feasibility of simultaneous bilateral endoscopic for
      tympanoplasty in patients with bilateral chronic suppurative otitis media.
      Method:Fifteen patients (30 ears) with bilateral chronic suppurative otitis media
      who underwent bilateral endoscopic transcanal tympanoplasty on the same day were
      enrolled in this study. The ear with worse-hearing was selected as the first
      operation side, the contralateral ear as the second one. The operation group
      consisted of 22 ears of Type 1 tympanoplasty, 5 ears of Type 2 tympanoplasty and
      3 ears of Type 3 tympanoplasty. All second sides(15 ears) underwent Type 1
      tympanoplasty. The cartilage-perichondrium graft was harvested from the tragal of
      the first side and was cut in two halves which could be used for the both sides.
      The graft success and hearing improvement were evaluated at the postoperative 6th
      month according to the follow up results of the endoscopic image and the pure
      tone audiometry. Result:The graft take rate was 96.7%(27/30) without any
      retraction pockets or displaced grafts. The graft take rate of the first side was
      93.3%(14/15), and the one of the second side was 100.0%(15/15). The average air
      conduction thresholds were (50.9+/-9.1) dB HL preoperatively and (32.0+/-6.0) dB
      HL postoperatively(P<0.01). The average air-bone gap overall improved from
      (30.2+/-7.9) dB HL preoperatively to (13.7+/-6.0) dB HL postoperatively(P<0.01).
      Conclusion:Bilateral same-day endoscopic tympanoplasty are safe and cost
      effective in appropriately selected patients. It can offer favorable out-comes in
      selected patients with chronic suppurative otitis media.

PMID- 30282175
TI  - [Cervical pharyngeal syndrome: a case report].
AB  - Summary Cervical pharyngeal syndrome is characterized by the symptom such as sore
      throat, foreign body sensation or swallowing discomfort which caused by the
      pathological changes of cervical intervertebral disc and intervertebral structure
      nonspecific injury. Because of the lack of obvious specificity, it is easy to
      misdiagnose. Here, we reported a case of cervical pharyngeal syndrome. The
      symptom were obviously improved after conservative treatment, but the follow-up
      time is short, and further follow-up is needed. In the process of diagnosis and
      treatment, in order to reduce misdiagnosis and mistreatment, we should strengthen
      the understanding of the disease, broaden the clinical thinking, and understand
      the anatomical relationship between the pharynx and the surrounding organs.

PMID- 30282176
TI  - [Complicated airway foreign body in a child: a case report].
AB  - Summary A 9 year-old boy suffering from cough for half a month, fever for 4 days
      was hospitalized. CT three-dimensional reconstruction showed that a metallic
      needle-like foreign body within the right main bronchial with pneumonia and
      atelectasis. In the next day, the boy took examination using an open-tube rigid
      bronchoscope under general anesthesia. For the first time, the foreign body was
      jammed in glottis with SpO2 and HR declining. For the second time, the operator
      found the foreign was not a needle but a thumbtack. Finally, the thumbtack was
      removed from the airway after short-term paralysis using succinylcholine.

PMID- 30282177
TI  - [A case of facial paralysis caused by granulocytic sarcoma of the external
      auditory canal].
AB  - Summary A male patients at 11 years of age, was hospitalized for the right ear
      pain and mouth deviation for five days on August 30, 2016, accompanied by right
      hypophasis, right ear hearing loss, tinnitus, without otorrhea and vertigo.
      Patient was diagnosed as acute promyelocytic leukemia in 2008. After standardized
      chemotherapy, it was completely relieved and the blood and bone marrow images
      were almost restored to normal. Physical examination: The skin of the right
      external auditory canal is obviously swollen, without rupture on the surface, and
      the tympanic membrane cannot be seen. The drooping of the left angle of the
      mouth, the right eyelid is not closed completely, the right nasolabial groove and
      forehead line is shallower. House-Brackmann facial nervous system III. Routine
      blood: the leucocyte 10.31*109/L, more than in the normal range. Pure tone
      measurement showed that right ear conductive deafness, air-bone conduction
      difference of each frequency range 50 to 75 dB.Mastoid CT showed that right
      mastoid gasification is good, the right external auditory canal, middle ear
      cavity and mastoid airway are filled with low-density soft tissue shadows, the
      bone wall of the external auditory canal was not significantly enlarged or
      damaged. The auditory bone is intact, surrounded by a large number of soft tissue
      shadows, no obvious abnormalities in the inner ear. Primary diagnosis: Middle ear
      cholesteatoma (right);External auditory canal tumor (right);Peripheral facial
      paralysis (right).

PMID- 30282178
TI  - [Advances in the treatment of anterior commissure combined with early glottic
      carcinoma].
AB  - Summary Early glottic laryngeal cancer usually refers to the Tis-T2 lesion
      without cervical lymph node and distant metastases. Radiotherapy of early glottic
      laryngeal cancer, CO2 laser microsurgery, open surgery, plasma radiofrequency
      ablation, photodynamic therapy, biological targeting therapy have achieved good
      therapeutic effect. However, due to the special nature of its anatomy, it is
      controversial about the treatment of early glottic laryngeal cancer which
      involves the anterior commissure. In this article, we reviewed the conventional
      treatment of radiation therapy, CO2 laser microsurgery, open surgery, plasma
      radiofrequency ablation.

PMID- 30282179
TI  - [Progress in diagnosis and treatment of vocal fatigue].
AB  - Summary Vocal fatigue is a common symptom of voice disease, but we prefer to
      regard vocal fatigue as a separate voice disease. In this paper, the etiology,
      pathogenesis and clinical diagnosis and treatment of vocal fatigue are reviewed
      in order to provide reference for the standardized diagnosis and treatment of
      this disease.

PMID- 30282180
TI  - [Precision prevention and treatment of allergic rhinitis].

PMID- 30282181
TI  - [Effect of intranasal excision under open the nasal vestibular flap on nasal
      vestibular cyst under nasal endoscopy].
AB  - Objective:Objective:To observe the clinical Effect of intranasal excision under
      open the nasal vestibular flap on nasal vestibular cyst under nasal
      endoscopy.Method:Forty-five patients with nasal vestibular cyst were randomly
      divided into two groups: nasal vestibule flap group (n=25) and labial gingival
      crevicular approach group (n=20).Comparison of two groups of patients with
      operation time, intraoperative blood loss, wound healing time, postoperative
      local numbness or pain, 1 week after eating the inconvenience, the degree of
      postoperative wound pain, postoperative facial swelling degree were compared
      between the two groups.Result:1The operation of the two groups was successful,
      and all patients were not relapse followed-up for 1-3 years and averaged 1.5
      years. 2Compared with labial gingival crevicular groove approach group,the amount
      of bleeding, wound healing time, postoperative upper lip numbness in local
      incidence, one week after operation of eating or the incidence rate of eating
      inconvenience pain aggravate in nasal vestibular double flap group with were all
      statistically significant (P<0.05).The operation time of the two groups were not
      statistically significant(P>0.05).3The degree of pain and swelling of the face in
      the nasal vestibule flap group were significantly lighter than that of the labial
      gingival crevicular approach group(P<0.05).Conclusion:Endoscopic resection of
      nasal vestibular cyst through nasal vestibule flap approach has advantages in
      less intraoperative bleeding,shorter wound healing time,much less postoperative
      local reaction, less pain and lower postoperative recurrence rate, and does not
      increase operative time.

PMID- 30282182
TI  - [Risk factors for recurrence of benign paroxysmal positional vertigo: a Meta
      analysis].
AB  - Objective:To investigate the risk factors for recurrence after otolith reduction
      of benign paroxysmal positional vertigo by Meta analysis.Method:The relevant
      literatures of risk factors for recurrence of BPPV were searched by the database
      of PubMed, Embase, OVID, Springer, Proquest. Revman 5.3 software was used to
      perform Meta analysis of the included literature. Result:A total of 15 articles
      were included in the final analysis and a total of 4 477 cases were included.
      Meta analysis results showed: the recurrent after otolith reduction of BPPV in
      patients with the hyperlipidemia and Meniere's disease increased significantly,
      compared to the patients without the hyperlipidemia and Meniere's disease,
      difference was statistically significant[OR=1.74, 95%CI(1.14
      2.65),P=0.01;OR=4.57,95%CI(2.78-7.52),P<0.01]. There was no significant
      difference in the recurrence after otolith reduction of BPPV in patients with
      diabetes and migraine compared without diabetes and migraine[OR=1.14,95%CI(0.84
      1.54),P>0.05; OR=0.99, 95%CI(0.66-1.47),P>0.05].Conclusion:Hyperlipidemia and
      Meniere's disease are risk factors for the recurrence after otolith reduction of
      BPPV.

PMID- 30282183
TI  - [Adult parapharyngeal and retropharyngeal abscesses:clinical features and their
      implications for treatment strategy].
AB  - Objective:To identify the clinical risk factors related to the increased
      likelihood of surgical drainage and medical therapy failure in parapharyngeal and
      retropharyngeal abscess. Method:The charts of 93 consecutive patients from
      January 2006 to April 2017 with parapharyngeal and retropharyngeal abscess were
      reviewed retrospectively. Logistic regression analysis was used to study the
      clinical risk factors.Result:A total of 97 adult patients, there were 34 cases in
      the immediate surgical drainage group and 32 cases in the delayed surgical
      drainage group and 31 cases treated with medical therapy alone. The rate of
      operation therapy was 68%,and the success rate of the medical therapy alone was
      32%. All patients had successful resolution of their abscesses by medical therapy
      and(or) surgical drainage. The average length of stay(17.26d) in the surgical
      drainage group was longer than the medical therapy group(10.26 d), and the
      difference was statistically significant(P<0.001).The maximum dimension of
      abscess>2.37cm is not only the risk factor of increasing likelihood of surgical
      drainage, but also that of medical therapy failure(P<0.001, P<=0.002).The factors
      affecting the hospitalization day were whether or not the operation was
      performed. There was no significant difference in operative rate between diabetic
      group and non?diabetic group(chi2=0.523,P>0.05).There were no correlation between
      diabetes mellitus and the multiple space abscesses(r=
      0.032,P<=0.760).Conclusion:Although a majority of adult parapharyngeal and
      retropharyngeal abscesses were treated with surgical drainage and sufficient
      effective intravenous antibiotics,but not all patients need surgical treatment.
      The diameter of the abscess is a risk factor affecting the operation or not.For
      those with larger abscesses,the preoperative preparation should be actively
      prepared and the operation should be intervened as early as possible;for those
      with smaller abscess,the treatment can be cured alone, and the surgical incision
      and drainage should be avoided in order to reduce the complications and shorten
      the hospital days.

PMID- 30282184
TI  - [The clinical value of wideband tympanometry in the diagnosis of otitis media
      with effusion].
AB  - Objective:To establish normative data for wideband absorbance measurements in
      Chinese with normal ear and effusion ear using wideband tympanometry(WBT) and
      determine the WBT curves of normal ears and effusion ears to facilitate the use
      of it. To investigate whether there are difference between the WBT absorbance in
      children aged 2-16 and adults above 16. To compare the sensitivity and
      specificity of WBT and conventional tympanometry tests for diagnosing otitis
      media with effusion (OME).Method:One hundred and seventy-six patients(342ears)
      ,from January 2015 to December 2015, were enrolled, including 96 males and 80
      females whose ages ranged from 2 to 74 years. All of these patients, who
      underwent physical examination, ear endoscopy, conventional tympanometry and pure
      tone audiometry, were divided into three groups, namely normal, negative pressure
      and effusion according to the clinical diagnosis. WBT was carried out in these
      patients to analyze whether there are difference in the absorbance between
      children and adults in normal ears.The absorbance diagram of normal, effusion and
      negative pressure ears were mapped in Chinese population.The normal WBT curve was
      named as type N (normal) curve, the middle ear effusion curve as type E
      (effusion) curve, and the middle ear negative pressure curve as type P (negative
      pressure) curve. Pairwise comparison was carried out to analyze the difference of
      the WBT absorbance among these WBT curves. Other 40 patients (66 ears) with
      clinical diagnosis of middle ear effusion, including 22 males and 18 females with
      ages ranged from 3 to 36 years old, underwent exploratory tympanotomy. These 40
      cases were detected preoperatively by both conventional tympanometry and WBT by
      which the sensitivity and specificity were compared in the diagnosis of middle
      ear effusion.Result:The normative data of WBT absorbance in Chinese with normal
      ear over 2 years old was established. The WBT absorbance at all frequencies
      between children and subject over 16 years old showed no statistically
      significant difference except for 10 frequencies in all 31 frequencies detected.
      The variations in the absorbance were mainly concentrated on the frequencies
      ranged from 500- 2000 Hz,in patients with OME. In the frequency range of 500-2000
      Hz, the absorbance amplitudes in type N curv >type P curve>type E curve. There
      were significant differences in WBT absorbance at all frequencies between type N
      and type E between within 500-2000 Hz.The sensitivity and specificity of WBT for
      middle ear effusion were 94.8% and 87.5%, respectively, which were higher than
      that of conventional tympanometry with 91.3% of the sensitivity and 62.5% of the
      specificity.Conclusion:The WBT absorbance is consistent at most of the
      frequencies in Chinese. The normal ear, effusion and negative pressure in the
      middle ear can be distinguished by WBT curve. WBT can be useful for clinical
      diagnosis of OME, which has a higher sensitivity and specificity than
      conventional tympanometry.

PMID- 30282185
TI  - [Measurement and analysis of cochlea in children with congenital sensorineural
      hearing loss with normal inner ear structure].
AB  - Objective:The cochlea of children with congenital sensorineural hearing loss with
      normal inner ear structure was measured and analyzed by high-resolution temporal
      bone CT(HRCT) imaging technique,its application value before cochlear
      implantation was evaluated and the appropriate electrode was selected.Method:We
      collected temporal bone HRCT images of 120 patients with congenital sensorineural
      hearing loss,according to gender divided into two groups,including 60 males and
      60 females.We used the PACS software to measure the distance A(the largest
      distance from the round window to the lateral wall) and the distance H(height of
      the cochlea) and calculate the cochlear duct length. Reproducibility of these
      data were evaluated and the results between the different groups were
      compared.Result:Measurement of parameter values between the intraobserver and
      interobserver showed great reproducibility. In the male children group,the
      measured values are shown as distance A[(8.55+/-0.31)mm],distance H[(4.57+/
      0.28)mm]and the cochlear duct length(CDL)[(27.59+/-1.23)mm]; and in the female
      children group, the measured values are shown as distance A[(8.45+/
      0.32)mm],distance H[(4.42+/-0.34)mm]and the cochlear duct length(CDL)[(27.20+/
      1.17)mm.The A,H,and CDL of the male cochlea were greater than those of the
      female, the difference was statistically significant(P<0.05).Conclusion:Measuring
      the distance A and distance H of the cochlea and calculating the cochlear duct
      length CDL can be used to select a suitable length of electrode or to customize a
      personalized electrode. This is a simple and effective assessment method before
      cochlear implantation..

PMID- 30282186
TI  - [Clinical features of papillary thyroid carcinoma patients associated with
      lateral lymph node metastasis in different ages].
AB  - Objective:To explore the clinical features of papillary thyroid carcinoma(PTC)
      patients associated with lateral lymph node metastasis(LLNM) in different ages.
      Method:One hundred and sixty?five PTC patients associated with LLNM were included
      in the study and divided into three groups(22-<30y,30-<45y and 45-65y). The
      gender, the number and the ratio of neck lymph node metastasis, maximum tumor
      diameter, multifocality, preoperative serum thyroid stimulating hormone(TSH), the
      capsular invasion, extrathyroidal extension and other clinical features in
      different ages were analyzed.Result:The median age of the patients was 39 years.
      There were no significant differences in the maximum tumor diameter
      >1cm,multifocality and preoperative serum TSH level among the three groups. The
      proportion of female patients in 22-<30y group was higher than the other two
      groups(all P<0.05).The rate of bilateral lesions in 45-65y group was higher than
      22-<30y group (P<0.01).The rates of the capsular invasion and extrathyroidal
      extension in 22-<30y group and 30-45 group were similarly lower than 30-<45y
      group(P<0.05).The proportion of the 22-<30y group coexistent with Hashimoto
      thyroiditis was higher than the other two groups(P<0.05). When the number of
      central lymph node metastasis(CLNM)>3,the proportion of 22-<30y group were higher
      than the other two groups(all P<0.01), the 30-<45y group was the same as higher
      than 45-65y group(P<0.05); When the ratio of CLNM>0.35,the proportion of 30-<45y
      group was significantly higher than the other two groups(all P<0.05).When the
      number of LLNM>6, 22-<30y group was significantly higher than the other two
      groups;when the ratio of LLNM>0.33, 45-65y group was lower than the other two
      groups(all P<0.05).The total lymph node metastasis>11, the proportion of 22-<30y
      group was significantly higher than the other two groups(all P<0.05), meanwhile
      30-<45y was higher than 45-65y group(P<0.05);when the ratio of total lymph node
      metastasis>0.22,45-65y group was significantly higher than the other two
      groups(all P<0.01).Conclusion: There is a high proportion of female and maximum
      tumor diameter over 1cm in PTC associated with LLNM. The proportion of coexistent
      with Hashimoto thyroiditis and the number of lymph node metastasis are much
      higher in 22-<30y group. The higher ratio of CLNM is much more common in 30-<45y
      group. The bilateral lesions are more likely to occur in 45-65y group, and
      meanwhile the tumor is more easier to invade the capsular and extrathyroidal
      construction. The number and the ratio of total lymph node metastasis might be
      lower in PTC associated with LLNM of older patients.

PMID- 30282187
TI  - [Comparison of the short-term and long-term curative effect and prognosis of 102
      patients with sudden deafness].
AB  - Objective:To compare the short-term and long-term curative effect and prognostic
      factors of 102 patients with sudden deafness.Method:The clinical data of 102
      patients with sudden deafness from 2012 to 2014 were analyzed retrospectively.
      Pure tone hearing thresholds were measured in patients with sudden deafness for 2
      weeks after treatment and 3 to 5 years after discharge, in order to evaluate the
      short-term and long-term effects, and related prognostic factors were also
      compared.Result:The short-term total effective rate of 102 patients with sudden
      deafness was 56.86%, and the long-term total effective rate was 69.61%.Under the
      same influence factors(female group, TG abnormal group,LDL abnormal group,HDL
      abnormality,blood rheology abnormality),the long-term total effective rate was
      greater than the short-term total effective rate(P<0.05),the difference was
      statistically significant.Further analysis of the influencing factors of the
      prognosis of sudden deafness found that audiogram shapes, blood rheology and
      blood lipid(TC,LDL,HDL),age,were the same prognostic factors of sudden deafness.
      Different audiogram shapes,normal and abnormal hemorheology group,normal blood
      lipid group and abnormal group,the curative effect of different age groups,the
      difference which the results of each group were compared was significant(P<0.05).
      However, there were differences between short-term and long-term prognostic
      factors.The short-term prognostic factors were also related to blood glucose and
      TG,the difference between normal blood glucose group and abnormal was
      significant(P<0.05). The difference between the normal TG group and the abnormal
      group was compared,the difference was significant(P<0.05).Conclusion:The long
      term curative effect of sudden deafness was better than that of the short-term.

PMID- 30282188
TI  - [Nystagmus characteristics of the horizontal semicircular canal light cupula].
AB  - Objective:To analyze the nystagmus characteristics of 9 patients with horizontal
      semicircular canal light cupula.Method:Patients who visited the department of
      otolaryngology of Shanghai sixth people's hospital from September 2017 to
      December 2017 with a typical history of positional vertigo and roll test evoked
      horizontal geotropic direction changing nystagmus that lasted more than one
      minute were enrolled in the study.Nystagmus was monitored using the
      videonystagmoscopy (VNG), and parameters of nystagmus,including latency, duration
      and the intensity of nystagmus were analyzed. Barbecue maneuvers were tried for
      all patients and no other treatment was performed.Result:Nine patients were
      enrolled,Dix?Hallpike test had no nystagmus, Roll test showed a persistent
      geotropic DCPN, the recorded average duration of nystagmus was (64.2+/-13.7)s
      (longer actually), and averaged latency was (5.3+/-4.7)s.In some cases,
      positional nystagmus increased rapidly in intensity and then declined slowly as
      seen in patients with canalolithiasis. Immediate effectiveness is 0 after
      barbecue maneuver,but 4 patients recovered within one week,2 patients improved
      within 1 week,and recovered within 2 weeks, 1 patient transferred into posterior
      semicircular canal BPPV, and 2 cases had not been followed
      up.Conclusion:Nystagmus of horizontal canal light cupula has a latency of several
      seconds,with a crescendo?decrescendo pattern of intensity.Barbecue maneuver may
      be not effective in resolving nystagmus,but the prognosis is good for those
      patients.

PMID- 30282189
TI  - [Clinical treatment of benign vocal cord lesions with occult vocal cord sulcus].
AB  - Objective:To discuss the correlation of benign vocal cord lesions with occult
      vocal cord sulcus and the treatment of benign vocal cord lesions with occult
      vocal cord sulcus, through the analysis of surgical data, preoperative voice
      evaluation data and postoperative follow-up data of patients.Method:The data from
      377 patients of benign vocal cord lesions with concealed vocal cord sulcus
      admitted to Beijing Tongren Hospital from 2005 to 2016 were reviewed. The follow
      up time was more than half a year after surgery.Result:About 2.9% of the benign
      lesions of the vocal cords were associated with occult vocal cords sulcus,of
      which 61.27% were bilateral vocal cords sulcus,22.55% was right vocal cords
      sulcus,and 16.18% was left vocal cord sulcus.Of the patients with bilateral vocal
      fold sulcus,64.5% had benign vocal cord lesions and 35.5% had unilateral vocal
      cord benign lesions.Of the patients with unilateral vocal fold,73.97% were
      associated with ipsilateral vocal cord benign lesions, and 26.03% were associated
      with contralateral vocal cord lesions.In the 531 sides of the vocal cords
      sulcus,183 sides of vocal fold sulcus typeIwere not treated. The 332 sides of
      vocal fold sulcus type II were treated with removed lesions of the vocal cords
      and microdissection of vocal cord adhesion.The 16 sides of vocal fold sulcus type
      III were treated with removed lesions of the vocal cords,local tamponaded of
      autogenous abdominal fascia and microsutured to close the wound. There were 9
      cases with 11 sides of vocal fold sulcus combined with the mucous bridge.The
      satisfactory rate of sound improvement was 80.37% in half a year after the
      operation.Postoperative fundamental frequency,jitter,shimmer and maximum
      phonation time were significantly improved compared with
      preoperative.Conclusion:The occurrence of benign vocal cord lesions may be
      related to occult vocal fold sulcus.Simultaneous treatment of benign vocal cord
      lesions with occult vocal cord sulcus can achieve satisfactory voice
      improvement.Therefore, we should pay attention to the treatment of vocal fold
      sulcus in the diagnosis and treatment of benign vocal cord diseases.

PMID- 30282190
TI  - [Value analysis of preoperative and intra-operative ultrasound in diagnosis and
      treatment of parathyroid adenoma].
AB  - Objective:To explore the value characteristics of preoperative and intra
      operative ultrasound in the diagnosis and treatment of parathyroid adenoma,and to
      further clarify the value of ultrasound in the diagnosis and treatment of
      parathyroid adenoma.Method:A total of 62 cases of parathyroid adenoma confirmed
      by postoperative pathology from March 2016 to November 2017 were collected, and
      the pre-operative ultrasound parameters were analyzed;and 26 cases were detected
      by intra-operative ultrasound.Result:In 62 cases of parathyroid adenoma, 58 cases
      of parathyroid adenoma were diagnosed by ultrasound before operation,and the
      sensitivity was 93.54%. Among the 26 cases,the lesions of 24 cases were detected
      by intra-operative ultrasound,and the sensitivity was
      92.31%.Conclusion:Preoperative ultrasonography has a high diagnostic value for
      the qualitative diagnosis and location diagnosis of parathyroid adenoma, and
      intra-operative ultrasound can help to detect lesions quickly and safely, which
      is of great significance to shorten the operation time and improve the safety of
      operation. It is an important development space of ultrasound in the diagnosis
      and treatment of parathyroid glands.

PMID- 30282191
TI  - [Analysis and surgical treatment of 72 cases of parapharyngeal space tumors].
AB  - Objective:To summarize and analyze the clinical features, diagnosis methods,
      surgical approaches and treatment outcomes of patients with parapharygeal space
      tumors.Method:A retrospective review of 72 cases with parapharygeal space tumors
      treated from March 1994 to June 2017 was performed. The data on presentation,
      surgical approach, histological diagnosis and postoperative complications were
      reviewed.Result:The postoperative pathological diagnosis included 62 benign
      tumors and 10 malignant tumors. The most frequent symptom was a cervical mass or
      an intraoral swelling. All patients underwent preoperative enhanced CT scan or
      MRI,which would be helpful to evaluate the tumor sizes,locations and possible
      sources,and to make operation scheme. The postoperative pathology included 24
      salivary gland lesions and 30 neurogenic lesions. The postoperative complications
      happened in 13 patients. The surgical approaches included trans-cervical approach
      in 55 cases, cervical-parotid approach in 9 cases,trans-oral approach in 6 cases
      , and trans skull base approach in 2 case.Conclusion:A parapharygeal space tumor
      is an uncommon tumor and requires careful preoperative assessment. Surgery is the
      first choice for parapharygeal space tumors. These patients should be counseled
      appropriately about the potential for permanent cranial nerve deficits.

PMID- 30282192
TI  - [Evaluation of quality of life on children with cochlear implants].
AB  - Objective:To provide theoretical basis for developing comprehensive and
      individualized rehabilitation programs,we evaluate the quality of life on
      children with cochlear implants(CI)and explore the influencing factors.Method:One
      hundred and three children with CI using the Mandaren children with cochlear
      implants: parental perspectives questionnaire were rated from communication,
      basic functions,independence ability, well-being,social relations, education,
      effect and influence of cochlear implants,and the support for children.The
      comparison was made according to different groups between duration of cochlear
      implants and age at assessment.Result:With the increasing of age at evaluation
      and the duration of cochlear implants,the scores of children in each dimension
      were also increased gradually.Four important factors affecting the quality of
      life of children with cochlear implants were the age at implantation,the duration
      of cochlear implants,the level of education with parents and the place of
      residence.Conclusion:The children with hearing impairment should use the cochlear
      implants as early as possible.While paying attention to the effect of
      postoperative hearing and speech rehabilitation,we should pay more attention to
      the evaluation of the quality of life,so that the children with cochlear implants
      can return to the mainstream society better.

PMID- 30282193
TI  - [Unilateral polyp originated from nasal septum: a case report].
AB  - Most polyps were originated from the contact areas of uncinate process, the
      middle turbinate or the ethmoid infundibulum. Polyp originated from nasal septum
      is extremely rare. We report a rare case of a 44-year old woman with unilateral
      polyp of nasal septum.

PMID- 30282194
TI  - [Primary small cell neuroendocrine carcinoma of the tonsil: a case report].
AB  - Neuroendocrine carcinoma(NEC) of the tonsil is extremely rare that exhibits
      highly malignant and poorly prognosis. Only a few of case reports and the optial
      treatment is still uncertain. Here, the current study presents a case of 60-year
      old male with neck mass rapidly growing for four months. It was diagnosed a
      primary tonsil neuroendocrine carcinoma. And he was treated by one cycle of
      cisplatin and etoposide. It had no effect and the tumor was rapidly progressed.
      With review of the literatures, the nomenclature, clinicopathological
      characteristics and treatment modalities of this rare tumor are discussed.

PMID- 30282195
TI  - [Adenoid cystic carcinoma of external auditory canal which pain as the first
      symptom:a case report].
AB  - Adenoid cystic carcinoma of external auditory canal is the relatively rare
      malignant tumor in head and neck surgery.As the signs and symptoms of this tumour
      do not always correlate with the histopathologic diagnosis and subsequent
      clinical behavior,it is easily to be ignored. Aggressive surgical resection with
      adjuvant radiotherapy seems effective for local disease control.

PMID- 30282196
TI  - [Advances in the role of adenoid hypertrophy in the pathogenesis of otitis media
      with effusion in children].
AB  - Adenoid hypertrophy(AH) and otitis media with effusion (OME) are both common
      diseases in pediatric otorhinolaryngology and are often associated with each
      other. Children are often diagnosed with otitis media with effusion and adenoid
      hypertrophy(OME/AH). Adenoids are immune lymphoid tissues of children's upper
      respiratory tract, and are important barriers against upper respiratory tract
      infections.During an upper respiratory tract infection,bacteria or viruses
      repeatedly stimulate immune lymphoid tissue to cause hyperplasia,and pathological
      hypertrophy is often accompanied by OME and other related symptoms.In recurrent
      or chronic OME, hyperproliferative adenoids are usually excised indicating that
      the two diseases may have a certain correlation. Recently,more and more studies
      have shown that AH plays an important role in the pathogenesis of OME in
      children. This article elucidates the role of AH in the pathogenesis of childhood
      OME from adenoid mechanical obstruction,adenoid bacterial and bacterial biofilm,
      adenoid local immune regulation, and IgE-mediated allergic reaction.

PMID- 30282197
TI  - [A brief introduction of local allergic rhinitis].
AB  - Local allergic rhinitis(local allergic rhinitis, LAR) is a newly proposed concept
      in recent years. It refers to patients with typical allergic rhinitis symptoms
      but skin prick test (SPT) and serum specificity IgE are negative, while nasal
      mucosa can produce local specific IgE and allergen provocation test (NAPT) are
      positive. The rate of clinical misdiagnose is high. The diagnosis mainly relies
      on typical nasal symptoms, positive NAPT and/or detection of local specific IgE.
      It needs to be distinguished from allergic rhinitis(AR) and non-allergic rhinitis
      (NAR). The main mechanism of its onset is the Th2-type allergic inflammatory
      response mediated by locally produced IgE. Eosinophils and mast cells are also
      involved in the inflammatory process. The current study considers LAR to be a
      separate disease from AR. Allergen immunotherapy(AIT) can be used to treat the
      disease..

PMID- 30282198
TI  - Reflective practice in psychiatric training: Balint groups.

PMID- 30282199
TI  - Five years of ECT: the relationship between consent status and treatment
      experiences.
AB  - OBJECTIVES: ECT has received limited systematic study in the Irish setting.
      Amendments to the Mental Health Act (2001) propose limiting the use of ECT to
      patients who can provide written informed consent. We report on the use of ECT in
      Limerick specifically addressing the issue of patient consent and how it relates
      to response rate. METHOD: Since 2003, the use of ECT within Limerick Mental
      Health Services has been monitored by a data gathering process that includes the
      documentation of mood disturbance before and after the procedure. RESULTS: In the
      five years between 2003 and 2007, 153 courses of ECT were given to 126 different
      patients (frequency 16.7/100,000; Female:Male = 2:1). The principal indication
      for ECT was depressive illness (95%). Bilateral electrode application was the
      preferred mode comprising 83% of use. A total of 60% experienced at least a 50%
      reduction in MADRS score over the course of ECT with 78% experiencing a reduction
      of 10 points or more on the MADRS. Higher response rate was linked to use of
      bilateral ECT (p = 0.007; 95% CI 1.3-13.6). A total of 14% of patients were
      unable to provide written informed consent and these patients had more severe
      depression at outset (p = 0.007; 95% CI 1.8-11.1) and a trend towards greater
      reduction in MADRS scores during ECT (p = 0.08). The commonest adverse incident
      associated with ECT was cognitive impairment (33 patients). The risk of cognitive
      problems was not related to age, ECT dose, number of treatments, severity of
      depressive symptoms, treatment response, or consent status. CONCLUSIONS:
      Frequency of use, response and adverse effect rates for ECT in Limerick Mental
      Health Services are similar to other centres. Cognitive impairment was the most
      frequent adverse event. The choice of electrode placement for ECT requires
      further consideration. Restricting ECT to patients that can provide written
      informed consent would prevent its use in many patients with severe illness who
      experience significant response to treatment.

PMID- 30282200
TI  - Reasons for referral and consultation liaison psychiatry diagnoses.
AB  - OBJECTIVES: Focused management strategies, including effective distribution of
      available resources is dependent on ongoing analysis of referral type in any
      liaison psychiatry consultation service. This survey sought to measure rate of
      diagnoses in an Irish liaison psychiatry consultation service, and compare the
      results with other similar services. METHOD: A survey of referral reasons and
      diagnoses was performed on all patients presenting to a Dublin based inpatient
      liaison psychiatry consultation service over two six month periods. The results
      were subsequently compared with other similar international studies. RESULTS:
      Commonest referral reasons were for depressive disorders, while commonest
      diagnoses included alcohol related disorders, depressive disorders, and delirium,
      with notably higher rates of alcohol related disorders than in other similar
      international studies. CONCLUSIONS: This study provides valuable information for
      referral reasons and diagnoses present in an Irish liaison psychiatry
      consultation service. The differences noted between diagnoses in our study and
      other international studies, as well as some of the difficulties in establishing
      these diagnoses, are discussed.

PMID- 30282201
TI  - Social and psychological correlates of happiness in 17 European countries.
AB  - OBJECTIVES: Happiness has been associated with a number of individual and
      societal factors, but much of the individual-to-individual variation in happiness
      remains unexplained. The purpose of this paper is to examine a broad range of
      social and psychological correlates of self-rated happiness in Europe. METHODS:
      We used data from the European Social Survey to determine levels of happiness in
      individuals (n = 30,816) from 17 European countries and to identify associations
      between happiness and age, gender, family relationships, satisfaction with
      income, employment status, community trust, satisfaction with health,
      satisfaction with democracy, religious belief and country of residence. RESULTS:
      Self-rated happiness varies significantly between European countries, with
      individuals in Denmark reporting the highest levels of happiness and individuals
      in Bulgaria reporting the lowest levels. On multi-variable analysis, happiness is
      positively correlated with younger age, satisfaction with household income, being
      employed, high community trust and religious belief. Overall, these factors
      account for 22.5% of the individual-to-individual variation in happiness in
      Europe. CONCLUSIONS: For the individual, this study highlights possible
      associations between happiness and the individual's attitudes towards various
      aspects of their personal, household and societal circumstances. For social
      policy-makers, this study suggests the potential usefulness of civic measures to
      increase community trust and social capital. Further studies of the inter
      relationships between individual and community-level variables would assist in
      further explaining the variance in happiness between individuals and countries.

PMID- 30282202
TI  - Stress in an Irish inner city emergency department revisited (2000-2006).
AB  - OBJECTIVES: Stress levels among staff in the Mater Misericordiae University
      Hospital Emergency Department were studied by questionnaire in 2000, which
      demonstrated a high level of self reported stress. The aim of this study was to
      ascertain if stress levels had reduced following changes in the department.
      METHOD: The study was repeated using the same questionnaire in 2006, after
      changes had occurred. RESULTS: There was a significant reduction in the
      percentage of staff that reported they were under severe or unbearable stress,
      from 37% in 2000 to 10% in 2006 (p = 0.002). A total of 60% felt the social
      environment of their work was satisfactory in 2006 compared to 40% in 2000 (p =
      0.03). Compared to 2000, a significantly lower proportion reported they had a low
      degree of control over their job, and a significantly higher proportion reported
      a medium level of control over their job in 2006 (p = 0.03). CONCLUSIONS:
      Compared with the results of the previous study, reported stress levels have
      reduced overall, which coincided with a significant increase in staffing levels
      in the department.

PMID- 30282203
TI  - Combined antipsychotic use in a community rehabilitation psychiatric service.
AB  - OBJECTIVES: Despite the clinical guidelines regarding the use of combined
      antipsychotics and the limited evidence for its benefits, use remains high in
      psychiatric practice. The aim of this study was to examine prescribing practices
      and investigate reasons for initiating and continuing combined antipsychotics in
      stable psychiatric illnesses. METHOD: A cross-sectional case record survey of
      antipsychotic prescribing practices in a community psychiatric rehabilitation
      service. A total sample (n = 75) of patients with chronic and enduring
      psychiatric illnesses was studied. The age, gender, diagnosis and prescribed
      antipsychotics were examined. The proportional prevalence and documented reasons
      for combined antipsychotic prescribing were analysed. RESULTS: Seventy-three of
      the 75 patients were prescribed antipsychotic mediations. Of these, 44 (60%)
      received a combination of two or more antipsychotics. The most common reason for
      combined prescribing was a switch of antipsychotic (n = 18; 41%). No reason was
      documented in 19 cases (43%). CONCLUSIONS: In this study, slow cross-tapering or
      incomplete switch process of antipsychotics contributed to the prolonged period
      of combined antipsychotics treatment. Adequate documentation regarding indication
      and review of medications cannot be overemphasized.

PMID- 30282204
TI  - Expenditure of compensation from legal claims in an opiate dependent population.
AB  - This study examined the expenditure of compensation received from legal claims by
      service users attending an outpatient methadone programme in Dublin. Most claims
      (n = 62) were as a result of road traffic accidents (74%) or personal injury
      (15%). There were 28 reports of claims resulting in payment of compensation
      totalling ?912,871. Of the compensation not placed in trust (?477,871), almost
      40% was spent on drugs and 8% on alcohol. Of those who reported no drug misuse at
      the time of the compensation being paid, seven out of 11 (64%) reported
      subsequently spending a significant amount on substance misuse. The risks of
      receiving large amounts of money in this population are substantial and include
      initiation and exacerbation of substance misuse, and risk of overdose.
      Alternative ways of managing the payment of compensation should be considered for
      this vulnerable population.

PMID- 30282205
TI  - An audit of incomplete involuntary admissions to an approved Irish centre.
AB  - OBJECTIVES: With the implementation of the Mental Health Act 2001 (M HA 2001) in
      November 2006, there was an expectation of reduction in the overall involuntary
      admission rate, particularly as those with a sole diagnosis of substance misuse
      were specifically excluded from the definition of mental disorder. The aim of
      this audit cycle was to ascertain this rate and to audit the process of the
      referral, transfer, assessment and subsequent management of the patients whose
      admission orders were not completed by the consultant psychiatrists (CPs)
      following referral for involuntary admission to an approved centre. In addition,
      the authors wished to ascertain if the recommendations of Audit 2003 were
      implemented. METHOD: The Audit 2003 analysed all Temporary Patient Reception
      Orders sent to an approved centre in the year 2003 but whose admission orders
      were not completed by the CP. A protocol was drawn up to elicit information. The
      Re-Audit in 2008 used the same protocol. The duration of the Re-Audit was
      01.11.06-31.10.07. The results were analysed using SPSS 12. RESULTS: There is no
      change in the involuntary referral rate to the approved centre in
      Longford/Westmeath since the new legislation was enacted. The CP continues to
      refuse to make an order in one in three cases. Patients with a sole diagnosis of
      alcohol misuse continue to be referred for involuntary admission but are now
      presenting sober on admission. There also appears to be an increased rate of
      incorrectly filled forms by GPs. CONCLUSIONS: This audit indicates a need for
      more training for GPs and Gardai in the MHA 2001 and filling of forms.

PMID- 30282206
TI  - Irish adolescents with ADHD and comorbid substance use disorder.
AB  - OBJECTIVES: To examine the literature for drug treatment of attention deficit
      hyperactivity disorder (ADHD) in adolescents with co-occurring substance use
      disorder (SUD), the challenges posed by this, and make recommendations taking
      into account current trend in Ireland. METHODS: Articles published from 1992-2008
      were identified using OVID-MEDLINE search using the search terms attention
      deficit hyperactivity disorder and substance use disorder. Studies cited include
      review articles, epidemiological studies, experimental researches, open and
      controlled trials of drugs in ADHD with comorbid SUD and clinical guidelines. No
      non-English language papers were included. RESULTS: Thirty-six studies were
      examined. A number of the papers reported on the link between ADHD and SUD, that
      they frequently co-occur, and there is evidence that treating ADHD can reduce the
      risk of future SUD. Some of the studies reviewed demonstrated the safety and
      effectiveness of ADHD medication on the ADHD symptoms but less so on the SUD.
      Concerns around stimulant abuse and diversion are valid. Although there is no
      current evidence of frequent diversion of ADHD medications in Ireland, this
      practice is prevalent in the US. Consequently psychiatrists should remain
      vigilant to the possibility of such diversions and take measures to address them
      if identified. CONCLUSIONS: The available evidence suggests that medication is
      not hazardous in ADHD comorbid with SUD. Pharmacological treatment of ADHD,
      following consideration of potential risks and benefits, is justified in the
      presence of SUD. Both methylphenidate and atomoxetine can be used. Stabilisation
      of serious SUD before pharmacotherapy is preferable, and it is advisable to
      provide psychological treatment to address SUD in these patients.

PMID- 30282207
TI  - A potential model for primary care mental health services in Ireland.
AB  - OBJECTIVES: A high demand for the inclusion of psychosocial interventions for
      primary care mental health presentations has become more apparent in recent
      years. Current policies have proposed models of care highlighting principles
      required for a quality service. However, implementation has been slow to date.
      This article aims to inform the current debate relating to primary care service
      delivery models for mental health presentations and to contribute towards future
      planning initiatives. METHOD: A narrative review of a range of policies and
      selected articles relevant to primary care mental health in an Irish context.
      RESULTS: The search produced four distinct themes: current service provision in
      Ireland; stakeholders' views; psychological care options; and potential service
      structures. Thereafter, a potential service delivery model is proposed. This
      formulated model employs a combination of elements from the reviewed themes to
      provide a clinically- and cost-effective, equitable and accessible service driven
      by service user and carer input. CONCLUSIONS: Although this review was selective
      in nature, the proposed potential model can complement future research agendas
      for more favourable primary care practice in Ireland. Recommendations are made
      for the planning of services including policy implementation procedures, training
      and communication.

PMID- 30282208
TI  - Depressive psychosis associated with a cyclo oxygenase 2 inhibitor (meloxicam).
AB  - We describe a 60 year old man who developed a fluctuating depressive psychosis
      associated with meloxicam, a non-steroidal anti-inflammatory drug (NSAID). The
      psychological symptoms observed were temporally related to the administration of
      meloxicam and occurred in the presence of signs of meloxicam intolerance, such as
      skin rash and raised blood pressure. The depressive reaction resolved quickly
      following cessation of meloxicam, recurring on re-exposure. The psychiatric
      manifestations of NSAID intolerance are rare, however 40% of cases have a history
      of mental illness. Data from adverse event reporting systems suggest that the
      newer NSAIDs (COX-2 inhibitors) may have a higher propensity to cause psychiatric
      adverse effects and should be used with caution in individuals with a history of
      mental illness. This data may be provocative given current research in to the use
      of COX-2 inhibitors in augmenting neuroleptic treatment in schizophrenia.

PMID- 30282209
TI  - Stammering and bipolar affective disorder.

PMID- 30282210
TI  - Basal ganglia MRI T1-weighted signal hyperintensities in an alcoholic patient.

PMID- 30282211
TI  - Use of Autism Diagnostic Interview (ADI-R) in clinical practice.

PMID- 30282212
TI  - Post-traumatic stress disorder: present and future.
AB  - Post-traumatic stress disorder (PTSD) and acute stress disorder (ASD) differ from
      almost every other psychiatric diagnosis in that they may only be diagnosed with
      reference to an aetiological event - an external traumatic stressor. ASD occurs
      immediately after the stressor and is comparatively short-lived, while PTSD is a
      prolonged abnormal response that may take months to develop. The types of
      stressor leading to ASD and PTSD are identical and were intended to be tightly
      defined, involving a perceived threat of death, serious injury or loss of
      physical integrity. It is useful initially to distinguish ASD and PTSD from
      adjustment disorders, which are also diagnosed only after an observable life
      event. An adjustment disorder may be thought of as a gradual and prolonged
      response to stressful changes in a person's life. The range of stressors
      precipitating an adjustment disorder is potentially much broader than that
      precipitating ASD or PTSD, as a threat of death or injury is not needed. Indeed,
      a 'threat' as such is not needed, as the event may be a loss. Events such as job
      loss or the breakup of a relationship may lead to an adjustment disorder, as well
      as threats such as accidents or assaults. The diagnostic criteria for adjustment
      disorder do not specify what the immediate response, if any, to the precipitating
      stressor must be.

PMID- 30282213
TI  - Facilitating journey to recovery.
AB  - The Irish 'Vision for Change', 2006 mental health policy document proposes a
      framework for promoting mental health and a recovery approach to inform every
      level of service provision. Comprehensive assessment by the rehabilitation and
      recovery multidisciplinary team with active involvement of the service user is
      crucial in the identification of needs, goals and recovery factors. This paper
      outlines importance of a comprehensive assessment tool, which helps to guide the
      service user towards identification and achievement of their goals while
      encompassing the recovery ethos.

PMID- 30282214
TI  - The economic cost of schizophrenia in Ireland: a cost of illness study.
AB  - OBJECTIVES: Although there are many published reports about the human cost of
      schizophrenia, there are far fewer estimates of its economic cost, particularly
      in Ireland. The aim of this study was to provide a prevalence-based estimate of
      the costs associated with schizophrenia in Ireland during 2006. METHOD: Using
      standard Cost of Illness (COI) procedures we compiled data from many sources
      including the Health Research Board, the Department of Health and Children and
      other government publications. Costs relating to health and social care, informal
      care, lost productivity, premature mortality and other public expenditures were
      included. Where national data were unavailable, we used bottom-up data from a
      geographically defined catchment area study and, in some instances, costs from
      two catchment areas were averaged. We did not measure human or intangible costs.
      RESULTS: The estimated total cost of schizophrenia was ?460.6 million in 2006.
      The direct cost of care was ?117.5 million and the burden of indirect costs was
      ?343 million. The cost of lost productivity due to unemployment, absence from
      work and premature mortality was ?277 million. Within indirect costs, the
      expenditure on informal care borne by families was ?43.8 million. CONCLUSIONS:
      Schizophrenia is not a very common condition but is an expensive one. This is
      attributable to its young age at onset, relatively low mortality rate and high
      severity particularly in terms of its impact on future employment. Measures to
      improve outcomes coupled with measures to improve employment such as supported
      employment strategies may impact significantly on the cost of schizophrenia. The
      study is limited because the national unit costs of many variables are not
      directly available and these Irish data are likely to be an underestimate.
      However, the results are comparable with a 2005 cost of illness study UK study.

PMID- 30282215
TI  - Children's depression, gender and age norms for an Irish national (primary)
      school population.
AB  - OBJECTIVES: To provide normative data for older national (primary) school
      children, broken down by age and gender, for the Children's Depression Inventory
      Short version (CDI-S) and revised norms for the Children's Depression Inventory
      Parent version (CDI-P) and its subscales. METHOD: Forty-three randomly selected
      national schools took part in this study. Participants were 1,255, fifth and
      sixth class, Irish national school children who completed the Children's
      Depression Inventory Short Form (CDI-S). In total 1,018 parents completed the
      corresponding parent form, the Children's Depression Inventory-Parent version
      (CDI-P). RESULTS: Norms for the CDI-S and the CDI-P subscales were produced.
      Revised norms for the CDI-P are proposed. Results revealed no significant age or
      gender difference in depressive symptomatology as measured by respondent's CDI-S
      and total CDI-P scores. Parent's ratings of their children's depression levels
      (CDI-P) and children's self-reported depression levels (CDI-S) were significantly
      correlated. The CDI-S and CDI-P displayed good internal reliability. CONCLUSION:
      Results indicate the utility of both the CDI-S and the CDI-P for assessing
      depressive symptoms in national school children in Ireland. This study confirms
      that national school children do display symptoms of depression. School based
      policies, materials and services supporting and promoting positive mental health
      should be developed, implemented and resourced.

PMID- 30282216
TI  - Bone mineral density and general health of long-term residential psychiatric
      inpatients.
AB  - OBJECTIVE: The aim of this study was to determine the rates of osteopenia and
      osteoporosis and other general health problems in a long-stay male psychiatric
      unit. METHOD: All 15 patients underwent a semi-structured clinical interview and
      a full physical examination including calculation of Body Mass Index, central
      obesity (abdominal circumference) and blood pressure measurement. All patients
      had blood sampling examining FBC, U&E, LFTs, TFTs, PSA, prolactin, lipid profile
      and glucose. The rates of metabolic syndrome were calculated according to the
      International Diabetes Federation consensus worldwide definition. Bone mineral
      density was determined in the lumbar vertebrae and left hip by DEXA scanning.
      RESULTS: The prevalence of osteopenia or osteoporosis was 46%, and bone mineral
      density was inversely correlated with serum prolactin levels (r = -0.595, p =
      0.041) and chlorpromazine equivalence (r = -0.645, p = 0.017). The prevalence of
      obesity was 53%, while central obesity was present in 87% of patients. Metabolic
      Syndrome was present in 27% of patients. CONCLUSIONS: More attention should be
      given to diagnosing and treating osteopenia and osteoporosis in patients on long
      term antipsychotic agents and preventative measures should form part of any
      treatment regime in these individuals. Frequent input from dietitians should also
      be available for long-stay psychiatric inpatients to reduce the prevalence of
      obesity.

PMID- 30282217
TI  - Ireland's long-stay charge refunds: mental capacity and dilemmas in a psychiatric
      institution.
AB  - OBJECTIVE: All patients who resided in state provided long-stay care in Ireland
      were required to pay the state for that care until 2006. In 2001 the Irish
      Ombudsman and Information Commissioner had highlighted the issue of the
      entitlement of people with medical cards to provision of free long-stay care. The
      Health Repayment scheme was subsequently set up in 2006 to facilitate the
      repayment of long-stay charges wrongly paid by patients. Issues of mental
      capacity arise particularly in the context of long-stay psychiatric patients
      applying for repayment of long-stay charges. Our aim was to devise a test
      suitable to assess the capacity of an individual to make an application for
      refund charges. METHOD: There was no specific test in existence to assess the
      capacity of an individual to make an application for refund of charges. A
      suitable test was devised based on the available literature which assessed
      whether the person understands the 'nature and effects' of making a refund
      application. Fifty-eight long-stay patients were deemed to be entitled to apply
      for a refund. RESULTS: Staff identified 47 (80%) patients as possibly lacking the
      capacity to make an application. Of these, 14 patients (29.8%) were found to have
      capacity to make an application (mean age 58.5 years) with 33 (70.2%) found to
      lack capacity (mean age 73 years). Of those with capacity 50% had a diagnosis of
      schizophrenia/schizoaffective disorder. None had cognitive impairment of
      degenerative origin. Of those who lacked capacity 45.5% had a diagnosis of
      dementia. All of the patients with dementia who were assessed were found to lack
      capacity whereas 59% of those with a diagnosis of schizophrenia/schizoaffective
      disorder lacked capacity. CONCLUSION: A substantial number of long-stay
      psychiatric patients may lack the capacity to make particular decisions. In this
      study the group who lacked capacity were an elderly group with dementia common.
      This process raised a dilemma about how a patient without capacity to make a
      refund application can then manage the money claimed on their behalf and whether
      guardianship safeguards are necessary.

PMID- 30282218
TI  - An exploration of the relationship between social support and depressive symptoms
      in schizophrenia.
AB  - OBJECTIVE: Depressive symptoms in schizophrenia have previously been associated
      with a perceived lack of social support. The aim of this study was to explore the
      relationship between perceived social support and depressive symptoms in
      schizophrenia; to assess the psychological wellbeing of their carers; and to
      examine the quality of the relationship between the patients and their carers.
      METHOD: Individuals with schizophrenia (n = 17) were assessed on the Beck
      Depression Inventory (BDI), the Beck Hopelessness Scale (BHS), a measure of
      perceived social support, the Significant Others Scale (SOS) and the Quality of
      Relationship Inventory (QRI). RESULTS: The mean score on the BDI for patients
      fell within the moderate-severe range and the mean range on the BHS fell within
      the moderate range. Family and friends were perceived as supportive resources by
      patients. There was no significant relationship between patient depressive
      symptoms or hopelessness and perceived social support. Carers of patients did not
      report high rates of depressive symptoms or hopelessness. CONCLUSIONS: These
      findings do not support the previous finding of an association between depressive
      symptoms and a perceived lack of social support in schizophrenia.

PMID- 30282219
TI  - Monitoring the physical health of individuals with serious mental illness.
AB  - Developing effective models of identifying and managing physical ill health
      amongst mental health service users has become an increasing concern for
      psychiatric service providers. This article sets out the general professional and
      Irish statutory obligations to provide physical health monitoring services for
      individuals with serious mental illness. Review and summary statements are
      provided in relation to the currently available guidelines on physical health
      monitoring.

PMID- 30282221
TI  - Primary care mental health - A new direction?

PMID- 30282220
TI  - Learning disability and forensic mental healthcare in 19th century Ireland.
AB  - The Irish College of Psychiatrists recently reported that "the needs of people
      with learning disability and offending behaviour pose a huge challenge to service
      providers. The vulnerability of people with a learning disability who come into
      contact with the criminal justice system is well described and noted." The
      College noted that "the population with learning disability who offend does not
      easily fit into existing services" and reported that "the majority of service
      providers strongly supported the urgent development of a forensic learning
      disability service." The challenges presented by individuals with learning
      disability and offending behaviour are not specific to Ireland or to this period
      in history. The purpose of the present paper is to explore issues related to
      learning disability and offending behaviour in 19th- and early 20th-century
      Ireland. More specifically, this paper presents original, previously unpublished
      case material from the archival medical records of the Central Mental Hospital,
      Dublin in order to illustrate specific aspects of the institutional experience of
      individuals with learning disability who were charged with offending behaviour in
      nineteenth-century Ireland. The Central Mental Hospital, Dublin was established
      as the Central Criminal Lunatic Asylum in 1845 under the provisions of the
      Lunatics Asylums (Ireland) Act (1845). Individuals were to be committed to the
      Central Criminal Lunatic Asylum if they were declared 'guilty but insane' at time
      of trial or offence, or if they developed mental illness and became difficult to
      manage while in detention elsewhere. The Central Criminal Lunatic Asylum opened
      its doors to admissions in 1850 and by 1853 there were 69 male and 40 female
      inpatients.

PMID- 30282222
TI  - Patient attitudes towards compulsory community treatment orders and advance
      directives.
AB  - OBJECTIVES: The Mental Health Act 2001 was implemented in Ireland in 2006,
      however, within this new legislation there is no provision for compulsory
      community treatment or advance directives, which are now established practice in
      other countries. We aimed to determine the proportion of patients who believe
      that compulsory treatment may be justified, the preference for where the
      treatment should be delivered and factors which may influence this preference. We
      also sought to determine the proportion of people who would be interested in the
      option of having an advance directive in their future care plan. METHODS:
      Patients who had been admitted involuntarily in a 183 bedded psychiatric hospital
      in Dublin (St John of God Hospital) over a 15 month period were interviewed one
      year following discharge. A structured interview was used and included the
      Birchwood Insight Scale and Drug Attitude Inventory (DAI). RESULTS: Sixty-seven
      patients were interviewed, which resulted in a follow-up rate of 68%. A total of
      56% of participants believe that there are situations in which involuntary
      treatment with medication may be justified. Of the participants 59% think that
      the person should be admitted to hospital if they are going to be administered
      medication without consent. A total of 41 % of participants stated they would
      have preferred to have been treated at home rather than hospital and this was
      associated with having a diagnosis of an affective disorder or it being their
      first involuntary admission. Of the participants 84% expressed interest in having
      the option of an advance directive in their treatment care plan. CONCLUSIONS:
      With the increasing community based provision of mental health services in
      Ireland a debate on compulsory community treatment orders and advance directives
      needs to take place amongst all stakeholders.

PMID- 30282223
TI  - Carer-rated needs assessment of a cohort of people with dementia.
AB  - OBJECTIVES: With increasing longevity, more people will develop dementia. These
      people will have a wide range of needs according to their circumstances. Services
      in the community struggle to meet these needs. This study aimed to identify needs
      of dementia sufferers attending the South Dublin Old Age Psychiatry service as
      rated by their carers, to assess the extent of unmet need and the implication of
      this. METHOD: The carers of 40 community-dwelling people with dementia attending
      the service were interviewed by one researcher using the Camberwell Assessment of
      Need for the Elderly (CANE). This measures a wide range of needs over 24 areas,
      from personal care, to social, financial and psychological care needs.
      Qualitative information was also obtained from carers regarding services
      available and their accessibility. A measure of carer stress and satisfaction
      with help for this was also obtained. RESULTS: Overall, the highest levels of
      need identified (both met and unmet) were in the areas of psychological
      functioning (memory and psychological distress), followed by social needs in the
      areas of managing money, daytime activities, self-care, and looking after the
      home. Highest unmet social needs were in the areas of daytime activities, home
      care and managing money. For 23/24 domains, carers were satisfied rather then
      unsatisfied with help received. The areas of greatest dissatisfaction to them
      concerned daytime activities, household skills and self-care. Over half of the
      carers reported psychological distress. CONCLUSION: High levels of need, both met
      and unmet were identified. Many identified needs related to the provision of
      community supports in the areas of selfcare, household skills and daytime
      activities, in addition to psychiatric needs. Assessment of needs is important to
      ensure adequate and responsive service provision, in keeping with the ethos of
      community care.

PMID- 30282224
TI  - Consultant psychiatrists' experience of workplace violence - a national survey.
AB  - OBJECTIVES: In recent years there have been a number of high profile cases in
      Irish psychiatry where consultant psychiatrists have been subjected to serious
      physical assaults. The last survey of assaults on consultant psychiatrists in
      Ireland was carried out in 1998. Therefore we sought to update the data on this
      topic. METHOD: An anonymous questionnaire was sent out by post to all consultant
      psychiatrists (n = 330) identified as currently working in the Republic of
      Ireland. RESULTS: The response rate was 48.2%. Sixty per cent of respondents were
      working in general adult psychiatry and respondents were evenly spread throughout
      the country. Ninety per cent of respondents had been the victim of verbal
      aggression/intimidation/threatening behaviour while 55% had been physically
      assaulted. The majority of incidents involved male patients aged between 21-40
      years with a diagnosis of paranoid schizophrenia. Nearly 66% of incidents of
      physical violence occurred during a relapse of illness. The perpetrator had a
      history of violence in approximately half of all reported incidents. Physical
      assaults tended to occur more commonly in inpatient settings (63.7%). Incident
      reporting occurred more often in physical assaults with 66% reported informally
      to colleagues and 20% reported to An Garda Siochana (police force of Ireland).
      Eighty-nine (56%) consultants described feeling 'safe' at work. Less than 50%
      reported the provision of standard safety equipment in the workplace and nearly
      half ofrespondents had not attended any safety training courses since their
      appointment. Longer experience working as a consultant psychiatrist did not
      appear to have an impact on reducing the rate of assaults. In addition, those who
      attended safety training courses did not report a reduced rate of physical
      assaults. CONCLUSIONS: These findings highlight the need for both organisational
      and personal changes in practice in order to reduce the assault rate.
      Organisational changes include the provision of appropriate safety equipment,
      safety training for consultants, enhancing multidisciplinary teams and utilising
      risk assessment. Consultants' personal practices to improve their safety may
      offer useful information for inclusion in safety training courses. This is an
      area which merits further research.

PMID- 30282225
TI  - Analysis of prescribing practices in an acute psychiatric ward.
AB  - OBJECTIVES: Prescription writing is a basic clinical skill for all doctors;
      however, errors in prescriptions are frequent and can result in significant harm
      to patients both from sub-therapeutic dosages and from over prescribing. This
      study examines the prescribing practices of 'as required' medications in an acute
      psychiatric inpatient unit attached to a university teaching hospital. METHOD: A
      clinical audit was conducted to examine both prescribing practices of 'as
      required' medication and recording of 'as required' medication in nursing notes.
      A series of educational interventions were undertaken in an attempt to improve
      prescribing practices in relation to 'as required' medication and two further
      audits were completed to assess any change in practice and whether such changes
      were sustained. RESULTS: Psycho-education led to an improvement in a number of
      prescribing practices, including increased generic prescribing, improved
      documentation of indications for medication administration and increased writing
      of medication dosages in acceptable abbreviations. These benefits were maintained
      four months after the education interventions. Rates of documenting the frequency
      of medication correctly and recording the administration of medication in nursing
      notes remained low. CONCLUSION: Our audit cycle clearly demonstrates that
      education can ameliorate prescribing practices and these improvements were
      maintained four months after education was delivered. However some aspects of
      prescribing practice remained deficient, and more focused educational
      interventions are required in these areas.

PMID- 30282226
TI  - Are you looking at me? Paranoid psychosis in pre-existing social phobia.
AB  - OBJECTIVES: Three patients presenting with a first episode of psychosis each had
      a past history of social phobia. We sought to explore the literature on the co
      occurrence of these disorders and investigate three hypotheses to explain this:
      (1) the chance co-occurrence of two illnesses with distinct aetiologies; (2) two
      clinical presentations reflecting different points on the same spectrum of
      illness; and (3) two distinct disorders representing different end points
      resulting from the same aetiology. METHOD: A literature review of Embase, PubMed
      and Psych Lit was performed. RESULTS: We found no reports on social phobia
      preexisting an episode of psychosis, and prevalence studies indicate that their
      chance co-occurrence is extremely unlikely. Psychological explanations for co
      occurrence include attributional theories, and theories related to cognitive
      biases and loss of self-esteem. CONCLUSION: There is a phenomenological overlap
      between social phobia and paranoia but the two concepts should and can be
      distinguished. Epidemiological studies indicate that their chance occurrence as
      two unrelated disorders is unlikely. Most people with one of these disorders do
      not develop the other and hypothesis (2) is also unlikely. There is increasing
      speculation that anxiety, and in particular social phobic symptoms have a central
      role in the development of psychotic symptoms. The greatest evidence was found to
      support hypothesis (3). However, it seems more likely that social phobia and
      psychosis, rather than representing manifestations of the same illness, instead
      are implicated in a complex interaction where symptoms which characterise social
      phobia and psychosis, have the capacity to affect, alter and possibly provoke
      each other. The recognition and treatment of co-occurring anxiety disorders,
      especially social phobia with psychosis, may have an important impact on
      prognosis and quality of life.

PMID- 30282227
TI  - Do we need community treatment orders in Ireland?
AB  - OBJECTIVES: Re-admissions to inpatient psychiatric care are now so frequent as to
      be designated the 'revolving door' phenomenon and constitute 72% of admissions to
      Irish inpatient psychiatric units and hospitals. It is commonly believed that
      treatment non-adherence with aftercare following inpatient discharge contributes
      to readmission. Attempts to improve adherence and reduce or shorten readmission
      through compulsory community treatment orders have been made in several countries
      including Scotland in 2005 and, from November 2008, England and Wales. Provision
      for conditional discharge in Ireland has already been furnished by the Criminal
      Law (Insanity) Act 2006 but has been compromised by the inability to impose
      enforcement of conditions. The paper aims to determine whether compulsory
      community treatment orders are effective in improving adherence and reducing re
      admission and whether, in consequence, their introduction in Ireland should be
      considered. METHOD: The legislative measures adopted to improve treatment
      adherence and thereby reduce re-admissions are presented. The evidence of their
      effectiveness is examined. RESULTS: Evaluation of the effectiveness of community
      treatment orders is limited and hindered by confounding factors. What evidence
      there is does not provide convincing evidence of their utility. CONCLUSIONS: It
      is concluded that there is insufficient evidence to advocate their early
      introduction in Ireland in civil mental health legislation. Instead a wait and
      see policy is suggested with critical assessment of the outcome of such
      developments in Scotland and England and Wales. In addition further research on
      the characteristics of revolving door patients in Ireland and the circumstances
      determining their readmission is advocated. There is an anomaly in the Criminal
      Law (Insanity) Act 2006 which allows of conditional discharge but does not
      provide for its enforcement.

PMID- 30282228
TI  - Bipolar affective disorder as the initial manifestation of multiple sclerosis.
AB  - The association between bipolar affective disorder and multiple sclerosis
      continues to be poorly understood in view of the limited knowledge and research
      in this field. Here we present the case of a 43 year old female with bipolar
      affective disorder who later developed multiple sclerosis. The relationship
      between the two disorders is discussed in the light of relevant and pertinent
      literature. It is hypothesised that bipolar affective disorder may be the
      presenting manifestation of multiple sclerosis and should be considered as a
      differential diagnosis in patients of bipolar affective disorder with
      neurological symptoms.

PMID- 30282229
TI  - Treatment considerations in clozapine induced enuresis or incontinence.
AB  - Antipsychotic related urinary symptoms are recognised and they remain a potential
      treatment-limiting sideeffect of clozapine. This article reports the incidence
      and management of two cases of clozapine-associated incontinence in
      psychiatrically stable patients. Both cases occurred during treatment and appear
      to have a similar pathophysiology, which may be related to the atypical nature of
      clozapine therapy. We searched the PubMed and MEDLINE databases for articles
      published from 1980 to 2008 that contain the keywords 'clozapine and enuresis,
      'clozapine and incontinence,' 'clozapine and seizures'. We also manually searched
      the bibliographies of these articles for related sources, and explored the
      reported treatment options to this side-effect of clozapine therapy. Both
      patients gave an informed consent.

PMID- 30282230
TI  - Inpatient care cost of schizophrenia in Ireland: underestimation due to non
      inclusion on data on new long-stay patients.

PMID- 30282231
TI  - Response to Dr Dixit regarding the economic cost of schizophrenia in Ireland.

PMID- 30282233
TI  - Psychiatry, hegemony and the myth of mental illness.

PMID- 30282232
TI  - The Dissociative Experiences Scale: Replacement items for use with the profoundly
      deaf.

PMID- 30282234
TI  - Morbid jealousy: The green-eyed monster.
AB  - Jealousy is a commonly experienced emotion which has been observed in infants as
      young as 5-6 months of age and across the lifespan of an individual. In its
      extreme form jealousy can be pathological, when the belief which may be a
      delusion, obsession or an overvalued idea, is held on inadequate grounds and is
      unaffected by rational discussion. Morbid jealousy differs from normal jealousy
      in its intensity or rationality. It can be thought of as hypersensitive jealousy
      since jealous reactions are experienced at a much lower threshold than in average
      individuals. Morbid jealousy is a disorder in which an individual believes that
      their partner is, or will be, sexually unfaithful. Morbid jealousy can occur when
      a partner is in fact being unfaithful, provided that the evidence for the
      infidelity is incorrect and there is an excessive or irrational response to such
      evidence. The preoccupation with the partner's infidelity is often triggered by
      vivid mental images of their partner's past or present relationships.

PMID- 30282235
TI  - Capacity legislation for Ireland: filling the legislative gaps.

PMID- 30282236
TI  - Psychiatric morbidity in male remanded and sentenced committals to Irish prisons.
AB  - OBJECTIVES: To describe the prevalence of psychiatric morbidity and the treatment
      needs of new committals to Irish prisons. METHODS: A population survey of 615
      prisoners representing 7.9% of male committals to Irish prisons in the year of
      survey, 313 remands (9.6% of total remand committals) and 302 sentenced
      committals (6.4% of total sentenced committals). The main outcome measures were
      ICD-10 diagnoses of mental disorder based on interviews using SADS-L and prison
      medical records. RESULTS: Current prevalence rates of any psychotic illness were
      3.8% (remand) and 0.3% (sentenced), six month prevalence rate 5.1% (remand) and
      2.6% (sentenced) and lifetime rate 9.3% (remand) and 6.6% (sentenced).
      Schizophrenia and drug/organic psychoses were the most common psychoses. Major
      depressive disorder had a current prevalence of 4.5% (remand) and 4.6%
      (sentenced), a six month prevalence of 4.8% (remand) and 6.0% (sentenced), and a
      lifetime prevalence of 8.6% (remand) and 15.9% (sentenced). Sixty-point-six per
      cent of the sample had a current substance misuse problem. CONCLUSIONS: There is
      significant psychiatric morbidity in committal prisoners.

PMID- 30282237
TI  - Psychogenic non-epileptic seizures in an Irish tertiary referral centre for
      epilepsy.
AB  - OBJECTIVES: To examine the prevalence, psychiatric co-morbidity and management of
      psychogenic non-epileptic seizures (PNES) in patients admitted to a tertiary
      referral Epilepsy Monitoring Unit (EMU). METHODS: Medical records of patients
      admitted to the EMU between 2003 and 2005 were examined and data from
      neurological, neuropsychiatric and neuropsychological assessments were analysed.
      RESULTS: Over a three year period 224 patients were referred to the EMU and 44
      (20%) were diagnosed with psychogenic non-epileptic seizures (PNES). A total of
      13 people (6%) were diagnosed with both PNES and epilepsy. Of those diagnosed
      with PNES 34 (75%) were referred to psychology services for cognitive behavioural
      therapy (CBT) and 26 (58%) were followed-up by psychiatry services. CONCLUSIONS:
      The prevalence rates for PNES and co-existing PNES and epilepsy are consistent
      with previous reports. Rates of psychiatric co-morbidity were less than would be
      expected in this clinical population. Clear evidence-based guidelines to manage
      people with PNES are required.

PMID- 30282238
TI  - Has the Mental Health Act 2001 altered the clinical profile of involuntary
      admissions?
AB  - OBJECTIVES: To assess whether transition from the Mental Treatment Act (MTA),
      1945 to the Mental Health Act (MHA), 2001 has had any impact on the clinical
      profile of patients in the West Galway Mental Health Services who are admitted on
      an involuntary basis. METHODS: Data were collected from clinical records in
      relation to all those individuals residing in the West Galway Mental Health
      Services who were admitted involuntarily in the 12 months prior to and subsequent
      to the introduction of the MHA 2001. RESULTS: A total of 175 individuals were
      included in this study (n = 91 - MTA 1945; and n = 84 - MHA 2001). No significant
      differences were found between the two groups in relation to demographic data,
      rates of involuntary detention or duration of involuntary detention. The
      applicant was less likely to be a family member under the MHA 2001 (54%) than the
      MTA 1945 (85%). CONCLUSIONS: Transition from the MTA 1945 to the MHA 2001 has had
      minimal impact on the admission rates, clinical profile or duration of detention
      of patients admitted involuntarily in the West Galway Mental Health Services.

PMID- 30282240
TI  - Implication of rates of referral to a specialised inpatient neuropsychiatry team.
AB  - OBJECTIVES: This study examined and compared the number and pattern of referrals
      from neurosurgery and neurology specialist services to the inpatient liaison
      neuropsychiatry service in the years 2002 and 2005. We estimated the prevalence
      of psychiatric illness and evaluated the results of subsequent psychiatric
      assessment and follow-up of all patients reviewed by the neuropsychiatry service.
      METHODS: The medical notes of those patients referred to the neuropsychiatry team
      were retrospectively examined to obtain appropriate information on assessment and
      management of these cases. RESULTS: There were 544 referrals over the two years
      selected for study. Rates of referral to the inpatient neuropsychiatry service
      increased overall by 35% between 2002 and 2005. Overall, referrals from neurology
      comprised 85%, neurosurgery 15%. Patients with epilepsy comprised the majority of
      referrals (36%). A total of 378 (73%) had an acute psychiatric disorder and this
      group had a significantly higher rate (p = 0.01) of past psychiatric disorder
      (40%) than that in those with no acute mental illness (33%). Depressive episode
      was the most frequent acute psychiatric diagnosis (38%), followed by anxiety and
      organic psychiatric disorder (both 15%). Overall, 21% of patients diagnosed with
      acute mental illness were referred on discharge to the neuropsychiatry outpatient
      clinic for specialist follow up and the remainder followed-up by either local
      mental health teams or their GP. CONCLUSIONS: These findings provide clear
      evidence that further resources should be allocated to expanding neuropsychiatry
      mental health services to improve detection and management of mental illness in
      this vulnerable patient group.

PMID- 30282239
TI  - Opiate substitution prescribing in Belfast - two year follow up study.
AB  - OBJECTIVES: The objectives of the study were to identify the characteristics of
      the patients who were commenced in a newly developed opiate substitute
      prescribing (OSP) programme, to determine their rate of retention and to
      ascertain the patients' opinions of the service. We also wished to determine
      rates of blood borne viruses in this population. METHODS: Data were collected
      from three sources: the Shaftesbury Square Hospital Substitute Prescribing
      Database, patient charts and an anonymous user views questionnaire. We also
      conducted viral screening. Inclusion criteria were opiate dependence according to
      ICD-101 for at least one year, in individuals who were 18 years of age or older.
      The sample comprised the first 80 patients who attended the service, who were
      followed up over two years. RESULTS: A total of 44% of our original cohort
      remained engaged with the service two years after commencement. Of the remainder,
      18% engaged with OSP elsewhere and 13% completed a successful detoxification from
      all opiate drug use. Factors which were associated with continuation in the
      programme were prescription of methadone (as compared with buprenorphine), female
      sex and higher doses of OSP. Patients reported high levels of satisfaction with
      the service. Of those who were tested for blood borne viruses, more than half
      were positive for hepatitis C infection. CONCLUSIONS: The response to the
      development of the opiate substitution programme demonstrated that there was a
      need in the community which had not been met in the past. Service users who
      attended the programme reported high levels of satisfaction.

PMID- 30282241
TI  - Dual diagnosis in a Dublin tertiary addiction centre - A cross-sectional study.
AB  - OBJECTIVES: To address the relative dearth of information relating to the
      prevalence of psychiatric co-morbidity among attenders of community addiction
      facilities. METHODS: We carried out a cross-sectional study of clients attending
      a Dublin-based tertiary addiction centre to assess the rates of psychiatric co
      morbidity, determine the demographic and clinical variables and evaluate the
      level of contact with allied medical care especially primary care and community
      psychiatric services. Information was sourced from available patient records.
      RESULTS: Forty-three per cent of the clients (n = 59), attending the service were
      found to have a chart diagnosis of psychiatric disorder. Only 15% of these were
      in contact with community psychiatric services. CONCLUSIONS: This high rate of
      psychiatric co-morbidity has implications in terms of funding, training and
      service delivery.

PMID- 30282242
TI  - Current psychotherapy training for psychiatry trainees in Northern Ireland.
AB  - OBJECTIVES: To investigate psychotherapy training for psychiatry trainees in
      N.Ireland. METHOD: A detailed survey of both trainee's current experience and
      completion of Royal College requirements. RESULTS: While trainees rated
      experience highly in terms of enjoyment and relevance to psychiatry, we found a
      large proportion (94%) were failing to meet requirements for psychotherapy
      training, despite awareness being high (91%). Both cognitive-behavioural and
      psychodynamic therapy were the predominant models of therapy trainees had
      experience in and although most supervision was rated highly, a number of
      trainees had irregular or no case supervision. CONCLUSIONS: At a time when it is
      becoming increasingly recognised that psychological therapies play a central role
      in the treatment of many psychiatric disorders, current training fails to provide
      a substantial experience. With such a high proportion of trainees not meeting the
      mandatory requirements and similar findings being replicated in other parts of
      the UK, serious consideration must be given to both the nature of the guidelines
      and the opportunities for psychotherapy training if future psychiatrists are
      going to be equipped to deliver a truly biopsychosocial model of care.

PMID- 30282243
TI  - 'Recovery' - towards integration into an Irish community mental health team.
AB  - OBJECTIVES: We aimed to further our understanding of the concept of recovery by
      analysing comments made in small group discussions that occurred on a planning
      Away Day held by a community mental health team along-side service users and
      carers, which had recovery as its theme. The purpose of this was to reshape the
      structure and workings of the team. METHOD: Five small groups, of approximately
      10 individuals each, comprised of service-users, carers, representatives from
      voluntary organisations and mental health professionals were asked to discuss
      three questions related to Recovery. RESULTS: The commentary reflected previous
      qualitative research on the philosophy of recovery. Issues that were raised
      included defining wellness as independent to illness, constructive risk taking,
      the importance of social factors, medication issues and the importance of self
      management and optimism. The comments subsequently went on to shape community
      mental health team service delivery. CONCLUSION: Discussion and reflection
      between mental health professionals, service users and carers can lead to a
      change in attitude and practice in a well-resourced, fully multi-disciplinary
      community mental health team, within which both the biological and non-biological
      aspects of mental illness are accepted. The result has been an introduction of
      service changes which have helped develop a team that is more accessible and
      increasingly collaborative.

PMID- 30282244
TI  - The borderlines of bipolar affective disorder.
AB  - This paper provides an overview of the major studies of bipolar affective
      disorder (BAD) and borderline personality disorder (BPD), and assesses whether
      the disorders might be better understood as variants of the same basic disorder.
      There is a shortage of research that delineates the features of both disorders
      within their representative samples. As a consequence the symptomatic overlap of
      the disorders, detected by categorical assessment instruments, is often
      misconstrued as an indication of the disorders' high rates of comorbidity (up to
      81%). In paying particular attention to features of both disorders, eg. affective
      instability and impulsivity, the paper provides evidence that BPD attenuates
      bipolar disorder along the spectrum of affective disorders, from non-classical
      bipolar presentation through to severe BAD with borderline features. The paper
      cites clinical, research and pharmacologic support of the contention that BPD,
      rather than representing a distinct disorder, is merely an attenuation of Axis I
      disorders, most especially bipolar affective disorder. Borderline personality is
      evident across the bipolar spectrum and exacerbates symptomatology and leads to
      poorer recovery prognosis.

PMID- 30282245
TI  - The Ennis District Lunatic Asylum and the Clare Workhouse Lunatic Asylums in
      1901.
AB  - The 1901 Census of Population returns provide a unique opportunity to examine the
      broad characteristics of institutionalised mental illness in one county over a
      century ago by complementing and extending the information contained in the main
      statutory source, the Report of the Inspector of Lunacy. This paper presents
      these characteristics as they relate to the first area on which such data have
      become publicly accessible - County Clare.

PMID- 30282246
TI  - New long-stay patients in Irish psychiatric inpatient services.

PMID- 30282247
TI  - Best evidence medical education and psychiatry in Ireland: a three step framework
      for change.

PMID- 30282248
TI  - Risk stratification and the care pathway.
AB  - OBJECTIVES: It was hypothesised that patients admitted to forensic mental health
      facilities are stratified along the pathway through care according to levels of
      need. Level of risk and psychopathology should vary with different levels of
      security. METHOD: Seventy-five men in a forensic hospital were interviewed by
      three trained clinicians using the HCR-20 (Historical Clinical Risk Assessment) -
      clinical and risk items, The Health of the Nation Scales - Secure (HoNOS-SECURE),
      PANSS (Positive and Negative Syndrome Scale), GAF (Global Assessment of
      Functioning) and the CANFOR (Camberwell Assessment of need Forensic Version).
      RESULTS: The mean scores on a variety of clinical measures were higher in
      admission/high security areas and progressively lower in rehabilitation and pre
      discharge areas. As patients moved through the pathways of care, they improved in
      a number of areas including psychiatric morbidity, risk, function, unmet needs.
      The following results stratified significantly; the HCR-20 summated clinical and
      risk (F = 9.2, df = 5, p < 0.001), the HoNOS secure (F = 18.2, df = 5, p <
      0.001), PANSS (positive, general and total), GAF, staff and user unmet needs on
      the CANFOR. CONCLUSIONS: The data indicate that the theoretical organisation of
      the units of the hospital into high, medium and low security units to form a
      coherent pathway through care is reflected in practice. This is a transparent
      route out of secure care in which restrictions are proportionate to risk and
      supports proportionate to need. It is unclear whether alternative models,
      consisting of a series of generic unstratified units for admission and discharge,
      all at the same level of therapeutic security, allow for the provision of
      treatment programmes and relational interventions appropriate to the patient's
      stage of recovery and rehabilitation.

PMID- 30282249
TI  - Management of patients' physical health in an acute psychiatric unit.
AB  - OBJECTIVE: The aim of this study was to help clarify the range of acute medical
      problems experienced by patients on an acute psychiatric unit during a period of
      28 days and nights, as encountered by psychiatric trainees, and to document any
      difficulties experienced by the trainee during these patient contacts. METHOD:
      This survey was carried out prospectively over 28 days and nights in an acute
      psychiatric ward attached to a teaching University Hospital. Following contact
      with an individual patient, the trainee recorded diagnosis, intervention and any
      difficulties encountered. RESULTS: Thirty-three patient contacts were recorded (n
      = 33). Trainees faced a range of primary care problems 22/33 (67%), but moreover,
      three patients demonstrated more serious and potentially life threatening
      problems, leading to 11/33 (33%) patient contacts requiring urgent interventions.
      CONCLUSIONS: While the debate continues as to who is best placed to provide
      medical healthcare for psychiatric patients, this study provides evidence that
      psychiatry trainees are required to draw on their previous medical and surgical
      experience on an almost daily basis. As psychiatrists we should consider our
      options on how best to manage medical problems on the acute psychiatric unit and
      consequently ensure confident liaison with our medical and surgical colleagues.

PMID- 30282250
TI  - Staff attitudes towards particular client difficulties in assertive outreach
      teams.
AB  - OBJECTIVE: Over recent years in England there has been widespread development of
      assertive outreach teams supporting patients with severe mental illness living in
      the community. Assertive outreach staff members are exposed to a variety of new
      stressors and risks. This study investigated the emotional impact on keyworkers
      of working with assertive outreach patients. This was considered in terms of the
      attitudes keyworkers hold towards patients with particular types of difficulty.
      The study also measured individual keyworker stress. METHODS: Keyworkers from
      three teams in Birmingham were surveyed regarding their attitudes towards
      individual patients. Questionnaires measuring attitudes and patient difficulties
      were derived for the purpose of the study. Strengths of attitudes were correlated
      against different patient difficulties. Keyworker stress was measured using the
      General Health Questionnaire, GHQ12. RESULTS: Certain patient difficulties, in
      particular poor engagement, psychotic symptoms and aggression were associated
      with feelings of failure in keyworkers whilst drug use, particularly crack
      cocaine use, was associated with fear of visiting patients at home. Some 41% of
      keyworkers met 'caseness' criteria on the GHQ12. Negative attitudes appeared to
      be independent of GHQ scores. CONCLUSIONS: Keyworkers expressed a number of
      positive and negative attitudes in relation to patient difficulties. Negative
      attitudes did not appear to be simply a feature of keyworker stress, however it
      is acknowledged that the sample size was small. Keyworkers' responses suggested a
      sense of personal failure when their patients were unwell or poorly engaged,
      despite patients being selected for assertive outreach on the basis of such
      difficulties. Recognition of negative attitudes may help in the improvement of
      training and supervision of staff members.

PMID- 30282251
TI  - Internal audit of attendances at a psychiatry outpatient clinic.
AB  - OBJECTIVE: This audit aimed to (a) systematically identify problems related to
      rates of attendance and non-attendance at one psychiatry outpatient clinic; (b)
      quantify these problems; (c) implement strategies to improve service delivery;
      and (d) re-audit after three months. METHODS: Specific standards were set in
      relation to patterns of attendance at the outpatient clinic. Audit was performed
      over two weeks; changes to practice were agreed and implemented for three months;
      re-audit was performed. RESULTS: The initial audit showed that (a) 93 people
      attended the clinic over two mornings with a non-attendance rate of 13.9%; (b)
      30.1% of individuals who attended did not have an appointment; (c) 20.4% of
      attendances were 'inappropriate'; (d) 2.2% did not live in the clinic's catchment
      area. Based on these results, the clinic introduced a protocol for individuals
      who attended without appointment; a protocol for streamlining the provision of
      prescriptions; and a renewed emphasis on transferring the care of individuals not
      residing in the catchment area. Three months later, re-audit showed that (a) the
      number attending over two mornings decreased from 93 to 43, but the non
      attendance rate had not changed; (b) the proportion of individuals presenting
      without an appointment (9.3%) decreased significantly compared to the initial
      audit (30.1 %); (c) the proportion of 'inappropriate' attendances (9.3%) tended
      to decrease compared to the initial audit (20.4%) but this was not statistically
      significant; (d) there was no difference in the proportion of patients who did
      not live in the catchment area; these proportions were low in both the initial
      audit (2.2%) and re-audit (2.3%). CONCLUSIONS: A relatively simple audit such as
      this can result in a more efficient and appropriate delivery of outpatient mental
      health services. On this basis, there is a need to provide ongoing resources for
      further cycles of clinical audit in mental health services.

PMID- 30282252
TI  - Neonatal outcome following buprenorphine maintenance for opiate dependency.
AB  - Methadone substitution improves maternal and neonatal outcomes. However methadone
      induced neonatal abstinence syndrome (NAS) is common. Buprenorphine-exposed
      neonates may be at a lower risk of NAS. Currently in the Republic of Ireland,
      buprenorphine does not have a special licence for use in pregnancy. We describe
      here the history and neonatal outcomes of the first Irish woman maintained on
      buprenorphine during two pregnancies. Supervised urinanalysis on this mother
      between and throughout both pregnancies did not reveal any illicit drug use. She
      delivered two post-term babies of normal birth weight and length. The second
      infant required treatment for NAS for 21 days with morphine sulphate. Although
      the use of buprenorphine in pregnancy does not remove the possibility of NAS,
      neonatal outcomes of buprenorphine-maintained women compares favourably to
      methadone. As the use of buprenorphine becomes more established in Ireland, the
      management of buprenorphine-exposed neonates will become more common.

PMID- 30282253
TI  - Primary progressive aphasia presenting as possible conversion disorder.
AB  - We describe a case of primary progressive aphasia (PPA) in a 62 year old right
      handed Irish woman who had progressive speech and language difficulty over a
      period of six years. She continued to work for a remarkable length of time and
      lived independently managing all her activities of daily living. The case posed a
      diagnostic challenge because initial presentation was suggestive of a conversion
      disorder. She also displayed signs and symptoms which overlapped with a fronto
      temporal dementia and possibly early Alzheimer's disease. In our discussion, we
      explore the possible reasons for this overlap and the implication for
      psychiatrists. The need for adequate and sensitive investigations and a multi
      disciplinary approach cannot be overemphasised as PPA cases are easily missed
      depending on the stage at which the patient presents.

PMID- 30282254
TI  - Drug combination with bupropion: a case of southern comforts.
AB  - A patient with a 20-year history of dysthymia had been treated with a range of
      anti-depressants over a period of two decades. He had experienced no clinically
      significant symptomatic relief for 14 years until he was recommenced on
      fluoxetine, a drug which had been of limited benefit to him previously. He showed
      no improvement in motivation, chronic anergia or easy fatiguability. He commenced
      an anti-smoking agent, bupropion hydrochloride (Zyban), without informing his
      treating psychiatrist and following the manufacturers' instructions, took the
      drug for four weeks, while initially continuing to smoke. He failed to
      discontinue smoking. However, his energy, motivation and general sense of
      wellbeing improved markedly, to the extent that his friends and colleagues
      commented upon the change. Bupropion hydrochloride is a well-known anti
      depressant agent not currently licensed for use in Ireland. His combination of
      fluoxetine and bupropion has improved his functioning to its best level in 20
      years. The improvement has been sustained for over six months. We examine the
      issues raised by this unusual combination, which I have termed 'southern
      comfort', in recognition of its geographical site of clinical impact.

PMID- 30282255
TI  - The lunatic asylums of Ireland 1825-1839.
AB  - OBJECTIVES: By the early 19th century the social manifestations of psychiatric
      disorder had become a matter of public and parliamentary pre-occupation in
      Ireland. This concern led to legislative provision for the establishment of a
      national system of district lunatic asylums. This paper describes some details of
      the early foundation of this system. METHOD: Examination of House of Commons
      papers on the lunatic asylums of Ireland 1835-1839. RESULTS: Details are
      presented concerning the activities, numbers of residents, admissions and costs
      of the 11 asylums in operation by 1839. CONCLUSIONS: By 1839 the operational,
      administrative and cultural characteristics of a national asylum system that
      would take another half century to complete and would extend well into the 20th
      century had been established.

PMID- 30282256
TI  - Drug and solvent misuse in national school children in mid-west Ireland.

PMID- 30282257
TI  - Multiple pathways on the route to recovery.

PMID- 30282258
TI  - The economic cost of schizophrenia in Ireland.

PMID- 30282259
TI  - Inpatient co-morbidity of mental illness and substance misuse (including
      alcohol).

PMID- 30282260
TI  - Adult deficit hyperactivity disorder and other diagnosis.

PMID- 30282261
TI  - Competency based training in Irish psychiatry.
AB  - The goal of undertaking postgraduate training in psychiatry is to become a
      competent specialist, and the educational model under which one is trained and
      assessed is crucial in achieving this goal. Over the years, traditional training
      models have emphasised what trainees know, over a given period of time, with
      outcomes assessed mainly by simple recall of knowledge. While these traditional
      approaches have met with varying levels of success, they are less than optimal
      when the goal is to train individuals to perform specific, job-related skills.
      This recognition has led to a global move towards competency based training
      models where the focus of training and assessment is the mastery of specific
      knowledge and skills as well as the conduct of the doctor in day-to-day clinical
      situations. In this article, a general overview of competency-based training in
      psychiatry is followed by a review of recent developments in Ireland in a global
      context.

PMID- 30282262
TI  - The Suicide Risk Assessment and Management Manual (S-RAMM) Validation Study 1.
AB  - OBJECTIVE: There are validated tools for structured professional judgement of
      risk of violence, but few for risk of suicide. The Suicide Risk Assessment and
      Management Manual (S-RAMM) is a new structured professional judgement tool
      closely modelled on the HCR-20. This is the first validation study for the S
      RAMM. We measured inter-rater reliability, internal consistency, concurrent
      validity with another validated risk instrument (HCR-20) and with a measure of
      psychopathology (PANSS). We tested whether the tool could distinguish between
      groups of patients clinically assessed as at varying levels of risk of suicide or
      self harm. METHOD: Two researchers jointly interviewed 25 current in-patients for
      inter-rater reliability (Cohen's kappa) and internal consistency (Cronbach's
      alpha) and interviewed 81 of 83 current in-patients to assess whether the mean
      scores for different wards were significantly different (using ANOVA). Two other
      researchers made independent ratings of the HCR-20 and PANSS. RESULTS: Inter
      rater reliability was acceptable for all items (Cohen's kappa >0.5 for all but
      three items) and all sub-scale and total scores (Spearman correlations all >0.8).
      Internal consistency was high, (Cronbach's alpha all sub-scales >0.6). Scores
      stratified significantly with high scores for admission and intensive care units
      and progressively lower scores in rehabilitation and predischarge units. The HCR
      20 historical and S-RAMM background scores did not correlate but the dynamic sub
      scales correlated significantly. PANSS scores also correlated significantly with
      S-RAMM scores. CONCLUSION: The S-RAMM has better than minimum acceptable
      characteristics for use as a clinical or research tool. Prospective studies of
      sensitivity and specificity are now required.

PMID- 30282263
TI  - Dialectical behaviour therapy in an Irish community mental health setting.
AB  - OBJECTIVES: Dialectical behaviour therapy (DBT) is a recommended treatment of
      patients with borderline personality disorder, yet there are few descriptions of
      the approach in public community mental health settings where the majority of
      such patients present. This study describes the development and evaluation of a
      DBT programme in an Irish setting. METHODS: The DBT programme was run over a six
      month period. Participants were assessed at baseline and post intervention with
      the following instruments: The Structured Clinical Interview for DSM III R
      personality disorders (SCID II), the clinical Outcomes in Routine Evaluation
      (CORE) and the symptom checklist 90 Revised (SCL-90-Revised). Inpatient bed usage
      was determined from case note review. RESULTS: Outcome data was available for
      eight subjects. Significant improvement (p < 0.005) was seen on all CORE
      subscales. SCL-90-R showed significant improvement (p < 0.05) on the global
      severity index and on the positive symptom distress index. A decrease in self
      harming behaviour was found. Subjects' inpatient bed days dropped from a mean of
      58 in the year pre intervention to a mean of four days in the year post
      intervention. A novel finding was that 43% of subjects who originally fulfilled
      criteria for avoidant personality disorder no longer did so post intervention.
      CONCLUSIONS: The study found that DBT can be applied in a community mental health
      setting with benefits similar to more specialist settings. Significant
      difficulties were encountered in implementing the programme. The clinical
      implications are that specialist psychotherapy services need to be an integral
      part of psychiatric services to achieve better outcomes for patients with
      borderline personality disorder.

PMID- 30282264
TI  - Characteristics and progress of patients who receive inpatient rehabilitation
      services.
AB  - OBJECTIVES: To describe the characteristics and progress of the first 50 patients
      with severe and enduring mental illness who accessed inpatient rehabilitation
      services in Dublin North East Mental Health Service between 2001 and 2006.
      METHOD: Retrospective collection of data on the first 50 inpatients from case
      notes and staff interviews. Data included demographics, psychiatric history,
      results of rehabilitation interventions and assessment tools. The results were
      compiled and analysed using descriptive statistics. RESULTS: Fifty patients were
      identified. The majority were male (68%) with a diagnosis of paranoid
      schizophrenia (60%). The levels of co-morbid alcohol and drug misuse were 40% and
      30% respectively. Histories of verbal/physical aggression were found in 92% and
      impulsive behaviour in 70%. The majority of patients had a past history of being
      detained under the Mental Treatment Act (1945). High levels of co-morbid physical
      health problems were identified. New long-stay (NLS) patients showed a trend
      towards requiring the shortest admissions prior to being ready for discharge to
      lower levels of support. CONCLUSION: One third of patients moved on to reside at
      lower support levels and accessed vocational training programmes following active
      inpatient rehabilitation interventions. However, there remained a cohort of
      patients who required prolonged inpatient admissions due to their high levels of
      disability. This study further highlights the need to ensure that a range of
      rehabilitation services from inpatient to supported community placement are
      provided to meet the needs of patients with severe and enduring mental illness
      with complex needs.

PMID- 30282265
TI  - Psycho-education of families in relation to their siblings' psychiatric illness.
AB  - OBJECTIVES: The aim of this study was to determine the extent of knowledge that
      family members of intellectually disabled individuals had in relation to their
      siblings' psychiatric illness. All siblings lived in residential intellectually
      disabled housing. METHOD: We evaluated on three occasions (before providing
      information about their sibling's psychiatric illness and treatment, and one and
      six months after providing this information) the families' understanding of their
      siblings' psychiatric illness. RESULTS: Initially families had a poor knowledge
      of their siblings' psychiatric illness and treatment, but this improved markedly
      after information was provided by a medical practitioner. This was a short-term
      effect, as at six months, families understanding had disimproved although not to
      pre-consultation levels. CONCLUSIONS: The provision of information to family
      members pertaining to their siblings' psychiatric diagnosis and treatment should
      be incorporated into the routine treatment of intellectually disabled individuals
      with a psychiatric illness.

PMID- 30282266
TI  - Comparison of referrals from primary and secondary care to CMHT psychologists.
AB  - OBJECTIVES: To explore whether (direct) referrals from GPs to two Community
      Mental Health Team (CMHT) clinical psychologists differed from those received
      from both 'Psychiatric' (eg. consultant psychiatrists) and 'Other' sources.
      METHOD: The two psychologists retrospectively examined and coded the case files
      of all clients who attended them during a 12-month period. The six measures used
      were diagnostic prevalence and groups, co-morbidity, chronicity, previous
      hospital admission and CMHT contact Separate cross-tabulations and chi squared
      tests were conducted for the various dependent variables to profile differences
      across the three referral sources. RESULTS: There was no difference in prevalence
      of Axis I disorders, co-morbidity and chronicity of disorders between 'GP' and
      'Psychiatric' referrals to the two CMHT psychologists. However, although low in
      number, there were more eating and psychotic disorders among the 'Psychiatric'
      referrals, and more of these referrals had previous hospital admission and CMHT
      contact. CONCLUSIONS: 'GP' referrals were similar to 'Psychiatric' referrals on
      some measures but differed on others. Hence, as to whether an 'open access' model
      of (direct) referral to CMHT clinical psychologists lowers the clinical threshold
      for referrals depends on which measures are deemed most critical. Consistently
      applying a composite index of referral 'severity' could prevent the former.

PMID- 30282267
TI  - Childbirth-related post-traumatic stress disorder and its treatment.
AB  - The phenomenon of childbirth-related post-traumatic stress disorder (PTSD) has
      become more widely recognised in recent years following changes in 1994 to the
      DSM criteria regarding how a traumatic event was defined. Emerging literature has
      predominately focused on prevalence rates and risk factors associated with this
      condition and on the use of debriefing techniques as an attempt to reduce or
      prevent the development of postnatal PTSD. However, little is known about the
      efficacy of psychological interventions that have been used to treat PTSD among
      postnatal women. This review summarises the limited evidence supporting the use
      of such treatments and discusses the significant challenges in developing and
      implementing psychological interventions for childbirth-related PTSD.

PMID- 30282268
TI  - Barriers to care in the mental health service: who gets in - who gets out?
AB  - "People with mental health problems are particularly vulnerable to social
      exclusion" - Vision for Change. People with mental health problems are very
      vulnerable. However those with mental health problems who have additional social
      problems are even more vulnerable. Currently psychiatric services in Ireland are
      provided on a 'catchment area' basis, with a consultant psychiatrist leading a
      multi-disciplinary team providing a service to the population of a defined
      geographical area. These services comprise both outpatient and inpatient care,
      and there is significant regional variation in terms of both bed availability and
      multidisciplinary team staffing. Sub-specialities, with the exception of child
      psychiatry and psychiatry of old age, are often unavailable, particularly outside
      Dublin. In such cases, some additional duties (eg. liaison, rehabilitation,
      perinatal) are assumed by the local general adult services. However, the overall
      distribution of services is uneven. Instead of services being concentrated upon
      those areas of greatest need, the opposite is often the case, with the most
      deprived areas having the least services in terms of acute beds and community
      mental health teams per thousand people. These areas also have less psychological
      services and specialist services despite increased levels of mental illness.
      Within this vulnerable population there are a number of sub-groups who are even
      further marginalised, and for whom there are significant barriers both at point
      of contact with services and with accessing appropriate follow up services. These
      include the homeless, the ever-increasing cohort of migrants to this country,
      those in prison and children and adolescents. Stigma and discrimination are the
      greatest barriers to social inclusion, quality of life and recovery for people
      with mental illness.

PMID- 30282269
TI  - Status epilepticus, electroconvulsive therapy and malignant melanoma.
AB  - Status epilepticus (SE), both convulsive and nonconvulsive, is a rare adverse
      effect of electroconvulsive therapy (ECT). This case report describes SE post-ECT
      associated with central nervous system (CNS) metastatic melanoma and reviews
      pertinent literature. The authors recommend that when CNS pathology is suspected,
      pre-ECT neurology consultation, neuroimaging, and EEG all may be indicated. This
      is especially important for patients with histories of primary cancers, such as
      melanoma, that metastasise to the brain.

PMID- 30282270
TI  - Brain biopsy and a case of dementia that wasn't.

PMID- 30282271
TI  - Zolpidem-induced somnambulism in an elderly man.

PMID- 30282272
TI  - Recent advances in the biological treatment of mood disorders.
AB  - Welcome to the first module in our Continuing Professional Development Section
      (CPD). CPD is now a key element in the clinical activity of all health
      professionals and a cornerstone of good clinical governance throughout mental
      health services. This section of the Irish Journal of Psychological Medicine will
      provide CPD modules dedicated to key topics in mental health care. In order to
      assist learning and self-assessment, multiple choice questions will be provided
      at the end of each module. This module and its multiple choice questions are
      available online on the website of the Irish Journal of Psychological Medicine
      (www.ijpm.org). The CPD policy of the College of Psychiatry of Ireland indicates
      that psychiatrists who participate in suitable online learning which fits the
      criteria for CPD may claim CPD points under the Personal CPD category (up to a
      maximum of 5 points per year). We are confident that this CPD Section of the
      Irish Journal of Psychological Medicine will prove to be a valuable resource for
      consultant psychiatrists, psychiatric trainees and all journal readers. We
      welcome feedback from readers and, especially, any suggestions for topics to be
      covered in future CPD modules. Suggestions should be emailed to:
      psychological@medmedia.ie.

PMID- 30282273
TI  - Electroconvulsive therapy, capacity and the law in Ireland.
AB  - The Mental Health Act (MHA) 2001 has major implications for treating patients
      with electroconvulsive therapy (ECT), especially as those referred for treatment
      are among the most severely ill and often lose capacity. Under the MHA 2001, a
      person may only be treated without consent if they are an involuntary patient.
      However, there is no provision in the Act for treating voluntary inpatients whose
      mental state has deteriorated but who do not seek to leave hospital. Such people
      may lack capacity to make treatment decisions but be passively compliant. The
      Wards of Court system is currently the only legal recourse but has been
      criticised by the Law Reform Commission and is unwieldy. Further legislation
      governing treatment of people lacking capacity to consent to ECT or withhold
      consent is required to protect and advance treatment of all concerned.

PMID- 30282274
TI  - Factors that influence patients' attitudes to antipsychotic medication.
AB  - OBJECTIVE: The aim of this study was to investigate the attitudes to medication
      in relation to insight, purpose in life, symptoms and sociodemographic factors
      among a cohort of stable patients with a diagnosis of schizophrenia and
      schizoaffective disorder. METHOD: We included 70 patients with a diagnosis of
      schizophrenia and schizoaffective disorder attending a Dublin suburban mental
      health service. All participants were 18 years or older and were excluded if they
      had a learning disability, acquired brain injury resulting in unconsciousness,
      and psychosis secondary to a general medical condition or illicit substance
      misuse. All participants were given self report questionnaires which included
      Drug Attitude Inventory (DAI-30), Birchwood Insight Scale, and Purpose in Life
      test. Symptoms were assessed using the Scale for Assessment of Positive and
      Negative symptoms. All data was analysed using the Statistical Package for the
      Social Sciences. RESULTS: We found that 86% (n = 60) of the participants had
      positive attitudes to medication, and 82% (n = 58) had good insight into their
      illness. Only 27% (n = 19) were found to have a definite purpose in life. There
      was a significant negative relationship between attitudes to medication and
      delusions (r = -0.25, n = 70, p < 0.05) and a significant positive relationship
      between insight and attitudes to medication (r = 0.0.28, n = 70, p < 0.05).
      CONCLUSION: Many factors are involved in the multifaceted issue of attitudes to
      medication. Researchers must realise that these factors do not remain constant
      and may change with time and over the course of illness and treatment.

PMID- 30282275
TI  - Psychopathology, insight and compliance in schizophrenia.
AB  - : Abstraact Objective: A four-week longitudinal study was conducted to assess the
      relationship between insight, psychopathology and treatment compliance in
      schizophrenia. METHOD: The study was conducted using Insight and Treatment
      Attitude Questionnaire (ITAQ), Positive and Negative Syndrome Scale (PANSS) and
      Medication Adherence Rating Scale (MARS). The sample comprised 50 patients with
      schizophrenia diagnosed according to research criteria of the International
      Classification of Diseases (ICD-10), with a mean duration of illness of 5.32
      years. RESULTS: Substantial psychopathology was observed at intake and it
      improved significantly at the end of four weeks. Similar changes were observed in
      the score of insight and of compliance over four weeks. The insight and the
      compliance were positively correlated to each other at the beginning and at the
      end of four weeks. Both of these were negatively correlated with psychopathology
      scores on both occasions. CONCLUSION: Insight and psychopathology remain
      important determinants of treatment compliance in schizophrenia over short term
      and long term follow up.

PMID- 30282276
TI  - Psychiatric illness and driving: Irish psychiatrists' documentation practices.
AB  - OBJECTIVE: Psychiatric illness and the use of psychotropic medication are
      recognised as factors that may impair driving ability. Clinicians in the UK have
      a legal duty to advise patients on the effects of illness and prescribed
      medication on driving ability. Although clinicians in Ireland have no equivalent
      legal obligations, good medical practice suggests that doctors should be aware of
      whether patients are active drivers, and issue appropriate advice, supported by
      adequate documentation in clinical notes. METHOD: The initial phase of the study
      analysed 44 outpatient records and 48 discharge records to ascertain the level of
      documentation regarding driving status, and advice given to patients regarding
      the effect of illness or medication on driving ability. The second phase involved
      distribution of an anonymous questionnaire to 18 psychiatrists employed in the
      acute psychiatric unit setting. RESULTS: Although there was minimal documentation
      regarding the potential effect of illness on driving ability, more than 50% of
      case notes revealed documented advice to patients regarding side-effects of
      medication and driving ability. Over 50% of case notes contained advice about
      medication compliance, but none contained cautionary advice about operating
      machinery. All psychiatrists admitted not being aware of the driving status of
      every patient they reviewed. Over 50% admitted to advising patients of the effect
      of illness or medication on driving ability, but fewer reported documenting this
      advice on every occasion. All psychiatrists reported that they would benefit from
      training in this area. CONCLUSION: This study suggests that there is
      underdocumentation of advice given to patients regarding the effect of their
      symptoms or medication on driving ability. Clinicians need to improve their
      awareness of patients' driving status, in addition to receiving training on what
      their responsibilities are in this regard.

PMID- 30282277
TI  - Non-attendance at new appointments at St James's Child Guidance Clinic.
AB  - OBJECTIVE: This study aimed to examine non-attendance rates at new appointments
      at St James's Child Guidance Clinic. METHOD: The sample consisted of all new
      referrals to St. James's Child Guidance Clinic in one calendar year (2004). Data
      was collected retrospectively from an electronic patient information system
      (Pinpoint), the new patient-referral logbook, referral letters, the appointment
      diary, and from clinical records. RESULTS: There were 260 new referrals to St
      James's Child Guidance Clinic in 2004. Out of the 260 children and adolescents
      granted a new appointment, 34 (13.07%) who failed to keep their appointment were
      identified. All patients granted an urgent appointment did attend. CONCLUSIONS:
      Non-attendance rates at new assessment in St James's Child Guidance Clinic were
      slightly lower than those reported in other studies. The implemented evidence
      based strategies to reduce non-attendance rates could explain the relatively low
      non-attendance rate at new assessment.

PMID- 30282278
TI  - Consultant psychiatrists' experiences and attitudes following the introduction of
      the Mental Health Act 2001: a national survey.
AB  - OBJECTIVE: This study explored the attitudes and experiences of consultant
      psychiatrists regarding the Mental Health Act 2001. METHOD: A postal survey was
      distributed to all consultant psychiatrists (n=238) in the Republic of Ireland.
      All specialties were included except Child and Adolescent Psychiatry. RESULTS: A
      response rate of 70% was achieved. Care of involuntarily admitted patients has
      improved according to 32%, but 48% found that the care of voluntary patients has
      deteriorated. Sixty-nine per cent of consultant psychiatrists acknowledge that
      involuntarily admitted patients are being changed to voluntary early to avoid a
      tribunal, and 21 % believe it occurs in over 40% of cases. Fourteen per cent of
      consultant psychiatrists have re-admitted a patient involuntarily immediately
      after a tribunal revoked the original Involuntary Order. Junior doctors' training
      by consultant psychiatrists has been reduced in 57% of placements as a result of
      the increased demands of the MHA 2001. Eighty-seven per cent report an increase
      in their on call service workload but only 23% report a sufficient increase in
      the number of consultants within their service. While 78% agree that patients
      should not be admitted involuntarily solely on the grounds that the person is
      suffering from a personality disorder, 58% feel that there is a risk in such
      patients not being involuntarily admitted in situations in which it is clinically
      necessary. Fifty-six per cent feel that there is a similar risk in patients with
      a diagnosis of substance misuse. CONCLUSION: Resources required to implement the
      Mental Health Act 2001 have not been sufficient leading to poorer quality of
      service and negatively affecting NCHDs training.

PMID- 30282279
TI  - Drug users' failure to modify alcohol consumption in response to hepatitis C.
AB  - OBJECTIVE: To measure (a) the prevalence of problem drinking in a population of
      methadone-treated drug users, (b) independent associations with problem drinking,
      (c) the effect of hepatitis C status on drinking behaviour, (d) the knowledge of
      drug users of their hepatitis C status and their perception of their drinking
      behaviour and (e) the attitude of drug users to the effect of alcohol on
      hepatitis C virus (HCV) related disease. METHOD: A cross sectional survey of 130
      drug users in treatment at the National Drug Treatment Centre, Dublin was carried
      out. A questionnaire incorporated the Alcohol Use Disorders Identification Test
      (AUDIT), and data were collected on sociodemographics, drug use history,
      perceived HCV status and drinking behaviour, and attitudes to the impact of
      drinking on HCV related disease. Hepatitis serology and drug urine data were
      collected from clinical records. RESULTS: The prevalence of problem drinking was
      41% (95% CI 33-51%). Unstable accommodation, older age, male gender and longer
      duration of heroin use were independent associations with being a problem
      drinker. There was no significant difference in the prevalence of problem
      drinking across HCV status. Knowledge of HCV status was accurate, however 35% of
      those identified as AUDIT cases failed to recognise their problem drinking.
      CONCLUSION: HCV infection among Irish drug users is compounded by a high
      prevalence of problem drinking with drug users failing to modify their drinking
      in response. Incorrect perception of problem drinking status could be a barrier
      to addressing this potentially remediable risk factor.

PMID- 30282280
TI  - Insight in mental illness: an educational review.
AB  - Insight is an elusive concept in psychiatry with a long history of divergent
      definitions and methods of measurements. Although insight was previously presumed
      to be a binary construct that an individual could possess or lack, there is an
      emerging consensus that insight is a multi-dimensional construct consisting of a
      spectrum of phenomena. Over recent years there has been increasing interest in
      the topic of insight, especially in relation to psychotic disorders where insight
      is frequently diminished. In this educational review we will discuss the history
      associated with the construct of insight, current theories in relation to
      insight, the association of insight with clinical symptoms and prognosis with
      particular reference to psychosis, the various methods of measuring insight, the
      aetiology of insight and present deficiencies in our understanding of insight.

PMID- 30282281
TI  - Mental capacity: legislation and medical treatment decisions in Ireland.
AB  - This paper examines mental capacity legislation in Ireland and its implications
      for medical treatment decisions for people whose capacities are believed to be
      impaired. It draws on inferences from case laws and legislations in other
      jurisdictions and concludes that there is an urgent need for the enactment of
      appropriate mental capacity legislation in Ireland.

PMID- 30282282
TI  - Philip Crampton (1777-1858) and his description of nominal aphasia.

PMID- 30282283
TI  - Information on co-morbidity on inpatient admissions.

PMID- 30282284
TI  - Methadone and its effect on QTc prolongation.

PMID- 30282286
TI  - Planning perinatal psychiatry services for Ireland.

PMID- 30282285
TI  - Community placement planning for a long stay in-hospital population.

PMID- 30282287
TI  - Recognition and management of Asperger's syndrome: perceptions of primary school
      teachers.
AB  - BACKGROUND: Most children who have Asperger's Syndrome (AS) are not identified
      until early school age, when social difficulties with other children become
      evident. Consequently, primary school teachers have an important role to play
      both in the recognition and management of the condition. OBJECTIVES: Our study
      sought to examine the perception of primary school teachers regarding the
      recognition and management of AS. METHODS: A structured questionnaire on the
      recognition and management of AS was circulated to all 90 primary school
      principals in the Fingal County of Dublin for them to copy and distribute to
      teachers in their schools for completion. Self-addressed envelopes were provided
      to each principal for the return of completed questionnaires. RESULTS: Three
      hundred and forty-three completed questionnaires were returned by 54 out of the
      90 school principals. Fifty-eight per cent of respondents reported that they had
      ever taught a child with the condition and 49% reported that recognition and
      management of emotional and behavioural disorders was covered in their
      undergraduate training. Some 78.4% said that they would recognise the symptoms of
      AS in a child, with those who had training on the recognition and management of
      emotional and behavioural disorders being more likely to report that they would
      recognise such symptoms while 71.1% said children with AS should be taught in
      mainstream classes. However, 77.3% did not think mainstream schools are presently
      adequately resourced to cater for children with AS. Some 96.2% said they would
      like to receive in-service training from the Child and Adolescent Mental Health
      Services on the detection and management of children with AS. CONCLUSION: There
      is a need for formal in-service training for all primary school teachers in the
      recognition and management of children with Pervasive Developmental Disorders
      (PDD). The recognition and management of children with PDD should also be
      included in the curriculum of all undergraduate teacher training institutions in
      Ireland.

PMID- 30282288
TI  - Deliberate self-harm (DSH) out of hour's presentations.
AB  - OBJECTIVE: To establish time of presentation to paediatric accident and emergency
      (A&E) services of children with deliberate self-harm (DSH). METHOD: All children
      presenting to an acute paediatric hospital with DSH or suicidal ideation between
      1993-2003 were identified and time of presentation collected from their case
      notes. RESULTS: Of the 172 children where the actual time of presentation was
      recorded, the majority of children - 137 (80%) presented to the hospital outside
      of the 'normal working hours' of 9am-5pm, Monday - Friday. These children
      represent an at-risk group, and were more likely to have consumed alcohol, to
      have made a suicide attempt, and to have a family history of psychiatric illness
      than children presenting with "normal working hours". CONCLUSION: DSH in young
      people is a significant public health problem in Ireland and is a major risk
      factor for completed suicide. Access to an out of hours on-call Child and
      Adolescent Psychiatry (CAP) services is essential if these children are to have a
      mental health assessment, as recommended by the Royal College of Psychiatry and
      National Institute of Clinical Excellence. These services need to be urgently
      developed.

PMID- 30282289
TI  - Prevalence and clinical correlates of depression in the acute phase of first
      episode schizophrenia.
AB  - BACKGROUND: Reported rates of depression in schizophrenia vary considerably.
      OBJECTIVE: To measure the prevalence of depression in a first episode sample of
      people with schizophrenia. METHODS: All referrals with a first episode of
      schizophrenia diagnosed using SCID interviews were assessed pre-discharge and
      again six months later. We used the Calgary Depression Scale for Schizophrenia
      (CDSS) and Positive and Negative Syndrome Scale (PANSS) to assess the severity of
      symptoms. RESULTS: Pre-discharge, 10.4% of the sample met CDSS criteria for
      depression. According to the PANSS depression (PANSS -D) subscale, 3% of patients
      were depressed, with a mean score of 7.48 (SD = 2.97). Only 3% of patients pre
      discharge were found to be depressed on both the CDSS and the PANSS-D. Six months
      later 6.5% were depressed according to the CDSS. However none reached depression
      criteria according to the PANSS-D. The CDSS correlated with PANSS-D both pre
      discharge and at follow-up. Feelings of depression and self-deprecation were the
      most common symptoms at baseline and follow-up. The CDSS was unrelated to
      negative symptoms at both stages. A lifetime history of alcohol abuse increased
      the risk for depression. CONCLUSION: Rates of depression in this sample were low.
      The CDSS appears to discriminate between depression and negative symptoms. Like
      the general population, alcohol misuse is a risk factor for depression in first
      episode schizophrenia.

PMID- 30282290
TI  - Medication adherence and knowledge in older patients.
AB  - OBJECTIVES: To assess the degree to which a sample of older individuals - who are
      engaged with psychiatric services - are knowledgeable about their medication and
      the reason for its prescription; to assess the degree to which these patients
      adhere to what is prescribed. METHODS: Convenience sample of 24 patients over 65
      years old, under the care of psychiatric services for Later Life, included.
      Patients who scored < 23 on Mini-mental State Examination were excluded. A
      questionnaire was administered which evaluated patients' knowledge of the names
      of, and reasons for, all prescription medications. Adherence rates were measured.
      Comparisons were made regarding to self-reported adherence rates and medication
      knowledge. These were based on diagnosis, age, number of medications prescribed
      and the presence or absence of sensory impairment. RESULTS: The median percentage
      of medication names recalled was 60%. A total of 25% of patients reported having
      some problem with adherence. No patient with a diagnosis of dementia was able to
      recall the names of, or reasons for, all medications prescribed. Patients with
      depression and dementia were as likely to be fully adherent as the total sample.
      Patients (a) aged 78 years or more and (b) those who were on more than six
      medications - were less knowledgeable about and less likely to adhere to
      prescribed drug regimens. We did not identify an association between reduced
      visual acuity and reduced medication adherence Conclusion: Patients require
      ongoing education concerning all aspects of medication, especially the reasons
      for prescription. Older patients and those receiving more complex regimens may be
      at particular risk of adherence problems.

PMID- 30282291
TI  - Association between antipsychotic medication and venous thromboembolism.
AB  - OBJECTIVE: This study aims to identify and review available evidence in the
      literature to determine the strength of association between antipsychotic
      medications and thromboembolism as an adverse effect. METHOD: Electronic
      databases were searched for evidence. RESULTS: A total of 15 case reports, 14
      case series, two observational studies and three case-control studies were found
      in the literature. Two case control studies found significantly increased risk of
      venous thromboembolism (OR 13.3 and 7.1 respectively). The risk was high for low
      potency antipsychotics. Studies were critically appraised to determine the
      strength of evidence. CONCLUSION: The studies reviewed indicate a significant
      association between antipsychotics and venous thromboembolism. Patients using the
      antipsychotics and those who prescribe them should be aware of this association.

PMID- 30282292
TI  - Reducing the revolving door phenomenon.
AB  - OBJECTIVES: De-institutionalisation and the expansion of community services have
      resulted in a reduction in the number of inpatient admissions in Ireland having
      fallen by 31% between 1986 and 2006. However, despite this, readmissions continue
      to account for over 70% of all admissions. The policy document A Vision for
      Change identified many shortcomings in the current model of provision of mental
      health services, making recommendations for the future development of community
      based services with emphasis on outreach components such as homecare, crisis
      intervention and assertive outreach approaches. These recommendations are
      reviewed in relation to readmissions and the impact they may have on reducing the
      revolving door phenomenon. METHOD: Three main intervention programmes essential
      to the delivery of an effective community-based service outlined and recommended
      by A Vision for Change, along with other pertinent factors, are discussed in
      relation to how they might reduce readmissions in Ireland. A series of Pearson
      correlations between Irish inpatient admissions rates and rates of outpatient
      attendances and provision of community mental health services are carried out and
      examined to explain possible relationships between increasing/decreasing
      admission rates and provision/attendances at community services. International
      literature is reviewed to determine the effectiveness of these intervention
      programmes in reducing admissions and readmissions and their relevance to the
      Irish situation is discussed. CONCLUSIONS: Whilst A Vision for Change goes a long
      way towards advocating a more person-centred, recovery oriented and integrated
      model of service delivery, it is apparent from the consistently high proportion
      of readmissions in Ireland that there are still many shortcomings in service
      provision. The availability of specialised community-based programmes of care is
      as yet relatively uncommon in Ireland and uneven in geographical distribution. A
      considerable improvement in their provision, quantitatively and qualitatively, is
      required to impact on the revolving door phenomenon. In addition a re
      configuration of existing catchment populations is required if they are to be
      successfully introduced and expanded.

PMID- 30282293
TI  - The Myth of Mental Illness: 50 years after publication: What does it mean today?
AB  - In 1960, Thomas Szasz published The Myth of Mental Illness, arguing that mental
      illness was a harmful myth without a demonstrated basis in biological pathology
      and with the potential to damage current conceptions of human responsibility.
      Szasz's arguments have provoked considerable controversy over the past five
      decades. This paper marks the 50th anniversary of The Myth of Mental Illness by
      providing commentaries on its contemporary relevance from the perspectives of a
      range of stakeholders, including a consultant psychiatrist, psychiatric patient,
      professor of philosophy and mental health, a specialist registrar in psychiatry,
      and a lecturer in psychiatry. This paper also includes responses by Professor
      Thomas Szasz. Szasz's arguments contain echoes of positivism, Cartesian dualism,
      and Enlightenment philosophy, and point to a genuine complexity at the heart of
      contemporary psychiatric taxonomy: how is 'mental illness' to be defined? And by
      whom? The basis of Szasz's doubts about the similarities between mental and
      physical illnesses remain apparent today, but it remains equally apparent that a
      failure to describe a biological basis for mental illness does not mean there is
      none (eg. consider the position of epilepsy, prior to the electroencephalogram).
      Psychiatry would probably be different today if The Myth of Mental Illness had
      not been written, but possibly not in the ways that Szasz might imagine: does the
      relentless incarceration of individuals with 'mental illness' in the world's
      prisons represent the logical culmination of Szaszian thought? In response,
      Professor Szasz emphasises his views that "mental illness" differs fundamentally
      from physical illness, and that the principal habits the term 'mental illness'
      involves are stigmatisation, deprivation of liberty (civil commitment) and
      deprivation of the right to trial for alleged criminal conduct (the insanity
      defence). He links the incarceration of the mentally ill with the policy of de
      institutionalisation (which he opposes) and states that, in his view, the only
      limitation his work imposes on human activities are limitations on practices
      which are conventionally and conveniently labelled 'psychiatric abuses'. Clearly,
      there remains a diversity of views about the merits of Szasz's arguments, but
      there is little diminution in his ability to provoke an argument.

PMID- 30282295
TI  - Tardive dyskinesia on low dose risperidone.
AB  - Tardive dyskinesia is a neurological disorder characterised by involuntary and
      purposeless movements affecting any part of the body. These movements typically
      occur in the oro-facial area and the patient is usually unaware of them. There
      are inconsistent findings in the literature on the risk factors for developing
      tardive dyskinesia. Nevertheless, previous reports indicate that tardive
      dyskinesia is more common in female patients, patients with a history of alcohol
      and substance misuse, affective disorders, and intellectual disability. The dose,
      class and duration of antipsychotic nmedication may also be independent risk
      factors. We report on the case of a patient who developed tardive dyskinesia on a
      low dose of the second generation antipsychotic risperidone.

PMID- 30282294
TI  - Absinthe and suicidality.
AB  - Absinthe is an alcoholic drink which is becoming more widely consumed after being
      banned for many decades. An association between absinthe use and psychiatric
      symptoms, ranging from impairment of concentration to marked hallucinations and
      seizures, has been suggested, but evidence remains unclear. Thujone, identified
      as a possible psychoactive ingredient, has recently been implicated in absinthe's
      putative neuropsychiatric effects. This report presents a case where acute
      suicidality emerged during absinthe consumption; possible neurobiological
      aetiological mechanisms and the history of absinthe use and associated adverse
      effects are reviewed.

PMID- 30282296
TI  - Cannabis and hyperemesis.
AB  - The adverse effects of marijuana are well documented, as well as its positive
      therapeutic uses. Cannabis has traditionally been associated with an antiemetic
      action following acute ingestion and synthetic cannabinoids have an established
      use as antiemetics for chemotherapy induced nausea. However, there has been
      limited recognition of chronic cannabis use as a cause of cyclic vomiting
      syndrome. Cannabinoid hyperemesis was first identified by Allen er al in 2004.
      Compulsive bathing was also described as part of the clinical picture. This same
      syndrome has been confirmed a number of times in the medical literature in the
      interim. The condition has, to our knowledge, never been reported, in a
      psychiatric patient.

PMID- 30282298
TI  - New long-stay patients in Irish psychiatric inpatient services.

PMID- 30282297
TI  - A missed opportunity: alcohol excise duty, RSA and trace-back.

PMID- 30282300
TI  - New long-stay patients.

PMID- 30282299
TI  - Impact of new long-stay patients on Irish psychiatric inpatient services.

PMID- 30282301
TI  - Adherence in psychiatry.
AB  - The word 'adherence' refers to the provision of consistent support (eg. for a
      political party or religion) or the act of holding particular elements together
      (eg. in constructing a building). In the medical context, adherence refers to the
      extent to which patients take their medications as prescribed. While the
      terminology related to medical adherence has changed significantly over the past
      two millennia, the core issue has not. Most recently, the term 'adherence' has
      replaced the term 'compliance', although it still jostles with 'concordance' in a
      growing literature which focuses now, as always, on one key question: why do so
      many people seek treatment for illness but then decide not to take their
      prescribed medication? This is an important question, both in terms of public
      health and societal cost: in the US, up to 50% of patients do not take their
      prescribed medications, resulting in additional healthcare costs of $290 billion
      per year. The greatest cost of non-adherence, however, relates to prolonged
      illness, increased rates of relapse and reduced wellness.

PMID- 30282302
TI  - Is there a role for suicide research in modern Ireland?
AB  - Suicide is a major public health issue of global concern. It is the leading cause
      of death in young Irish men, marking suicide and suicidal behaviour as important
      topics for clinical epidemiology and public health research. Ireland has a
      statutory obligation from the "Reach Out" policy document to "systematically plan
      research into suicidal behaviour to address deficits in our knowledge" (pp. 50).
      Suicide is undoubtedly a complex phenomenon and therefore one which requires
      advanced methods of investigation and innovative approaches to research the
      factors underpinning suicide in modern Ireland, the development and evaluation of
      prevention strategies and the informing of evidence-based policy.

PMID- 30282303
TI  - The Suicide Risk Assessment and Management Manual (S-RAMM) Validation Study II.
AB  - OBJECTIVES: Structured professional judgement is now the most widely accepted
      approach to clinical risk assessment and risk management. The Suicide Risk
      Assessment and Management Manual (S-RAMM) is a new structured professional
      judgement tool closely modelled on the HCR-20. This is the first prospective
      validation study for this instrument. METHODS: Two post-membership registrars
      jointly interviewed 81 of 83 current inpatients to rate the S-RAMM. Two assistant
      psychologists independently rated the HCR-20, GAF and PANSS. All incidents of
      self-harm, attempted suicide, suicide and violence to others were collated from
      hospital reporting of critical incidents over the next six months supplemented by
      examination of other records. RESULTS: For combined self-harm and suicide
      outcomes, the S-RAMM total score using the receiver operating characteristic had
      an area under the curve AUC=0.89, (95% CI 0.79 to 0.99). The S-RAMM performed as
      well for the prediction of self-harm and suicide as the HCR-20 did for violence,
      and better than measures of mental state (PANSS total score) and global function
      (GAF). CONCLUSIONS: The S-RAMM has better than minimum acceptable characteristics
      for use as a clinical or research tool for suicide risk assessment, and performs
      almost as well as the HCR-20 does for violence. Further prospective studies are
      now required, in other populations.

PMID- 30282304
TI  - Deliberate self-harm in young people: attendance at a paediatric emergency
      department.
AB  - OBJECTIVES: Deliberate self-harm (DSH) is the strongest predictor of suicidal
      behaviour. This retrospective study reviewed all DSH presentations to our
      Paediatric Emergency Department between 2002-2006. METHOD: Using database and
      medical records we profiled these presentations. Data was coded and statistically
      analysed. RESULTS: There were 253 DSH attendances. Twenty-four percent were
      living in care, 15% were under 12 years and 14% presented more than once.
      Overdoses (61%) were more common than cutting (16%) and 56% had a psychiatric
      condition. CONCLUSIONS: DSH presents an ongoing challenge to child and adolescent
      mental health services and those working in suicide prevention. Identifying the
      characteristics of these young people is essential to providing appropriate
      treatment for this high-risk group.

PMID- 30282305
TI  - The distribution of wellbeing in Ireland.
AB  - OBJECTIVES: There is a substantial knowledge gap about the distribution of mental
      health in community populations. The European Social Survey is particularly
      useful as it contains information on over 40,000 individuals, including 2,286
      Irish adults. The objective of this study is to conduct a large scale statistical
      analysis to examine the distribution and determinants of mental wellbeing in a
      large representative sample of the Irish population. METHOD: Analysis of the
      European Social Survey using robust multiple linear and non-linear regression
      techniques. The data-set contains WHO-Five scores and subjective wellbeing for a
      sample of 2,286 Irish people interviewed in their homes in 2005. RESULTS: Ireland
      has the second highest average WHO-Five score among the 22 countries in the
      European Social Survey. Multiple linear regression analysis across the
      distribution of WHO-Five reveals a wellbeing gradient largely related to
      education and social capital variables. A probit model examining the determinants
      of vulnerability to psychiatric morbidity reveals that a similar set of factors
      predict scores below the threshold point on the WHO-Five scale. CONCLUSIONS: The
      results are consistent with marked differences in mental wellbeing across
      education levels and variables relating to social capital factors. Such
      indicators provide a useful index for policy-makers and researchers. However,
      much further work is needed to identify causal mechanisms generating observed
      differences in mental health across different socioeconomic groups.

PMID- 30282306
TI  - Client satisfaction among outpatients attending an Irish community mental health
      service.
AB  - OBJECTIVES: To assess patient satisfaction with mental health services. Client
      satisfaction with mental health services is attracting increasing attention and
      is now considered a key outcome variable in evaluating mental health services.
      The Quality Framework (Mental Health Commission (MHC)), and Vision for Change
      (VFC) support such evaluation. However, there are no published quantitative data
      from Irish users of a community mental health service. METHOD: We invited
      outpatients attending a Dublin community mental health service to complete a
      standardised self-report instrument (Client Satisfaction Questionnaire, CSQ-8)
      and provide qualitative feedback. RESULTS: Of the seventy-nine respondents, 80%
      report they were 'satisfied' or 'very satisfied' with the service. However, they
      were critical of; access to, operation of, and communication with the mental
      health services. CONCLUSIONS: Although satisfied, when given the opportunity to
      comment, service users can be critical of aspects of the service they receive.
      Only using quantitative evaluation of outpatient client satisfaction levels may
      fail to capture important consumer suggestions for service development. Recent
      recommendations and upcoming changes would address a number of the criticisms of
      mental health services identified in this study.

PMID- 30282307
TI  - Neuropsychology and its relevance to clinical psychology in the non-specialist
      adult mental health setting.
AB  - OBJECTIVES: This study aims to investigate the prevalence of neuropsychological
      disorders in a non-specialist clinical psychology service in adult mental health
      service and also to explore the existence of neuropsychological symptoms in those
      subjects having psychiatric disorders. METHOD: The yearly data of new referrals
      from the psychology register and record files of the patients was collected for
      this purpose and subsequently analysed. The two content scales of MMPI-2, ie.
      HEA2 and HEA3 were administered and scored. RESULTS: The results indicate that
      neuropsychological disorders were the second major referral source during this
      period and a significant difference (p = 0.001) was found between the scores of
      HEA-2 and HEA-3, which suggest that the subjects reported more neuropsychological
      symptoms than symptoms of general health concern during their initial routine
      psychological assessment. CONCLUSION: There is consistency in our findings
      regarding the questions raised in this study which indicates a prevalence of
      neuropsychological disorders in adult mental health settings. It also indicates a
      high rate of neurological symptoms in psychiatric patients with psychiatric
      disorders.

PMID- 30282308
TI  - An audit of new long-stay patients in Irish psychiatric inpatient services.
AB  - OBJECTIVES: The most recent census of psychiatric inpatients (Daly and Walsh,
      2006) examined the decline of the long-stay population (both new and old long
      stay) from 1963 to 2006. The aim of the present study was to identify new long
      stay patients (patients in hospital between one and five years) in the 2006
      psychiatric in-patient census and follow them up one year later to determine the
      number remaining as inpatients, ie. not having been discharged Methods: New long
      stay patients were extracted from the 2006 psychiatric inpatient census data base
      and were followed up one year later. RESULTS: Sixty-eight per cent (315/460) of
      new longstay patients on 31/03/06 were still resident in units and hospitals one
      year later on 31/03/07, the majority in psychiatric hospitals Forty-two per cent
      (133/315) of patients had a primary diagnosis of schizophrenia, 13% (40/315) of
      depressive disorder, 11% (33/315) of organic mental disorder and 8% of
      intellectual disability (24/315). The number of new long-stay patients discharged
      or who died showed a sharp decline on previous years. CONCLUSIONS: Unless current
      services are improved and extended as advocated in A Vision for Change, it will
      be a number of years before this population leaves psychiatric hospitals and such
      hospitals can close because of the lack of suitable alternatives. In accordance
      with policy recommendations, the continuing requirement for the development of
      specialised rehabilitation services to cater for the broad needs of those who
      remain in psychiatric hospitals is of the utmost importance.

PMID- 30282309
TI  - CBT for adolescent pathological gambling - lessons from adult research.
AB  - OBJECTIVES: Features of gambling, particularly among young people have changed
      over the past decade and, while there are no data from Ireland, there are
      suggestions from those working in the field that pathological gambling is
      increasing among adolescents. Relatively little is known about the effective
      treatment of pathological gambling in adolescents. This paper aims to review
      research in cognitive behavioural treatments with a view to their application in
      adolescents. Research among adolescence is given prominence when this is
      available. METHODS: The methodology comprised a literature search of Medline,
      Psycinfo, and EMBASE databases, using the search terms: 'cognitive behavioural
      therapy'; 'gambling; 'psychology'; 'epidemiology'; 'adolescent'; 'motivation';
      'effectiveness'; 'outcome'; 'relapse'; and 'internet'. In addition, a hand search
      of Clinical Psychological Reviews, Journal of Gambling Studies, Addiction,
      Psychology of Addictive Behaviors, and International Gambling Studies (1997-2007)
      was performed. RESULTS: A total of 23 studies comprising various cognitive and
      behavioural approaches were identified, all but three of them confined to adult
      subjects. Study methodology and quality varied greatly, with many case studies or
      small case series, and only three randomised control trials. None used an
      intention-to-treat analysis, and there was little long-term follow-up. Almost ail
      indicated, with more or less evidence, that cognitive behavioural strategies
      might be beneficial. CONCLUSIONS: Many varieties and modifications of cognitive
      behavioural therapy have been applied to pathological gambling, though there are
      few studies of any psychological treatments for adolescent gamblers.
      Methodological problems surround much of the research. Notwithstanding these
      reservations cognitive behavioural approaches seem to offer promise in managing
      this serious problem.

PMID- 30282310
TI  - Clozapine induced myocarditis: a case report and literature review.
AB  - Clozapine, the drug of choice for treatment resistant schizophrenia, has a range
      of serious cardiac side-effects. This paper describes a fatal case of myocarditis
      in a 48 year old man four weeks after starting clozapine. In particular, this
      case illustrates how incipient the disorder can be and the need for a high level
      of suspicion. Difficulties in diagnosing clozapine induced myocarditis and ways
      to minimise its risk are also discussed.

PMID- 30282311
TI  - Pulmonary embolism secondary to clozapine therapy.
AB  - Clozapine is an atypical antipsychotic indicated for paranoid schizophrenia
      (treatment resistant type). However its use has been limited by the well
      established association with neutropenia and agranulocytosis. It has also been
      suggested that clozapine therapy is associated with other serious adverse effects
      such as fatal myocarditis or cardiomyopathy.

PMID- 30282312
TI  - The economic cost of schizophrenia in Ireland.

PMID- 30282313
TI  - New executive clinical director posts in Ireland.

PMID- 30282314
TI  - Lead (Pb), intellectual functioning and health.

PMID- 30282315
TI  - The changing face of ADHD.

PMID- 30282316
TI  - Current approaches to the management of schizophrenia.
AB  - Welcome to the second module in our Continuing Professional Development Section
      (CPD). CPD is now a key element in the clinical activity of all health
      professionals and a cornerstone of good clinical governance throughout mental
      health services. This section of the Irish Journal of Psychological Medicine will
      provide CPD modules dedicated to key topics in mental health care. In order to
      assist learning and self-assessment, multiple choice questions will be provided
      at the end of each module. This module and its multiple choice questions are
      available online on the website of the Irish Journal of Psychological Medicine
      (www.ijpm.org). The CPD policy of the College of Psychiatry of Ireland indicates
      that psychiatrists who participate in suitable online learning which fits the
      criteria for CPD may claim CPD points under the Personal CPD category (up to a
      maximum of 5 points per year). We are confident that this CPD Section of the
      Irish Journal of Psychological Medicine will prove to be a valuable resource for
      consultant psychiatrists, psychiatric trainees and all journal readers. We
      welcome feedback from readers and, especially, any suggestions for topics to be
      covered in future CPD modules. Suggestions should be emailed to:
      psychological@medmedia.ie.

PMID- 30282317
TI  - Copper radiopharmaceuticals for theranostic applications.
AB  - The growing advancement in nuclear medicine challenges researchers from several
      different fields to integrate imaging and therapeutic modalities in a theranostic
      radiopharmaceutical, which can be defined as a molecular entity with readily
      replaceable radioisotope to provide easy switch between diagnostic and
      therapeutic applications for efficient and patient-friendly treatment of
      diseases. For such a reason, the diagnostic and therapeutic potential of all five
      medical radionuclides of copper have thoroughly been investigated as they boost
      the hope for development of successful radiotheranostics. To facilitate the
      mutual understanding between all different specialists working on this
      multidisciplinary field, we summarized the recent updates in copper-based nuclear
      medicine, with specific attention to the potential theranostic applications.
      Thereby, this review paper is focused on the current achievements in the copper
      related complementary fields, such as synthetic and nuclear chemistry, biological
      assessment of radiopharmaceuticals, design and development of nanomaterials for
      multimodal theranostic implications. This work includes: i) description of
      available copper radionuclide production methods; ii) analyses of the synthetic
      strategies for development of improved copper radiopharmaceuticals; iii) summary
      of reported clinical data and recent preclinical studies from the last five years
      on biological applicability of copper radiopharmaceuticals; and iv) illustration
      of some sophisticated multimodal nanotheranostic agents that comprise several
      imaging and therapeutic modalities. Significant advancement can be seen in the
      synthetic procedures, which enables the broader implication of pretargeting
      approaches via bioorthogonal click reactions, as well as in the nanotechnology
      methods for biomimetic construction of biocompatible multimodal copper
      theranostics. All this gives the hope that personalized treatment of various
      diseases can be achieved by copper theranostics in the near future.

PMID- 30282319
TI  - A comprehensive review on xanthone derivatives as alpha-glucosidase inhibitors.
AB  - alpha-Glucosidase plays an important role in carbohydrate metabolism and is
      therefore an attractive therapeutic target for the treatment of diabetes, obesity
      and other related complications. In the last two decades, considerable interest
      has been given to natural and synthetic xanthone derivatives in this field of
      research. Herein, a comprehensive review of the literature on xanthones as
      inhibitors of alpha-glucosidase activity, their mechanism of action, experimental
      procedures and structure-activity relationships have been reviewed for more than
      280 analogs. With this overview we intend to motivate and challenge researchers
      (e.g. chemistry, biology, pharmaceutical and medicinal areas) for the design of
      novel xanthones as multipotent drugs and exploit the properties of this class of
      compounds in the management of diabetic complications.

PMID- 30282318
TI  - Synthesis and structure-activity relationship studies of cruzain and rhodesain
      inhibitors.
AB  - Chagas disease and Human African trypanosomiasis (HAT) are important public
      health issues in Latin American and sub-Saharan African countries, respectively,
      and are responsible for a significant number of deaths. The drugs currently used
      to treat Chagas disease and HAT present efficacy, toxicity, and/or resistance
      issues; thus, there is a clear need for the discovery of novel targets and drug
      candidates to combat these diseases. In recent years, much effort has been made
      to find inhibitors of cruzain and rhodesain, which are promising targets for the
      design of novel trypanocidal compounds, since they are essential for parasite
      survival. Many reviews covering the design of novel cruzain and rhodesain
      inhibitors have been published; however, none have focused on the chemistry of
      the inhibitors. Thus, in the present work we reviewed the synthetic strategies
      and routes for the preparation of relevant classes of cruzain and rhodesain
      inhibitors. Perhaps the most important are the vinyl sulfone derivatives, and a
      very efficient synthetic strategy based on the Horner-Wadsworth-Emmons reaction
      was developed to yield these compounds. Modern approaches such as the asymmetric
      addition of substituted ethynyllithium to N-sulfinyl ketimines were used to
      produce the chiral alkynes that were employed in the preparation of important
      chiral triazole derivatives (potent cruzain inhibitors) and chiral HPLC
      resolution was used for the preparation of enantiopure 3-bromoisoxazoline
      derivatives (rhodesain inhibitors). Moreover, we also highlight the most
      important activity results and updated SAR results.

PMID- 30282320
TI  - Dimetallic Ru(II) arene complexes appended on bis-salicylaldimine induce cancer
      cell death and suppress invasion via p53-dependent signaling.
AB  - A series of bis-salicylaldimine ligands bearing two ON-donor functions were
      reacted with dichloro(p-cymene)ruthenium(II) dimer in the presence of base
      (NaOAc) and a series of four dimetallic Ru(II) arene complexes (Ru(p
      cymene))2(bis-salicylaldimine)Cl2 (C1C4) were prepared. These complexes were
      obtained in excellent isolated yields and characterized in detail by using
      different spectroscopic techniques. The structure of C1 was also determined in
      solid state by single crystal X-ray analysis. These complexes were studied for
      their cytotoxic effect against three different types of human cancer cells
      including hepatocellular carcinoma (HepG2), non-small-cell lung cancer (A549) and
      breast cancer (MCF-7) cells by MTT assay. These complexes showed considerable
      cytotoxic effect in all the above-mentioned cell lines that was comparable to the
      effect of cisplatin. C1 and C2 showed moderate anticancer effect while C3 and C4
      showed reasonable cytotoxicity. We found the cytotoxicity was increased in series
      from C1 to C4 representing the effect of ligand modification from small to bulky
      group at the amine functionality of the salicylaldimine. We selected C3 and C4
      for mechanistic anticancer study in MCF-7 cells. The acridine orange/ethidium
      bromide and DAPI staining assays of MCF-7 cells treated with Ru(II) complexes
      showed apoptosis in cancer cells. Similarly, these complexes induced p53 protein
      expression in MCF-7 cells. Further, increased mRNA levels of p63, p73, PUMA, BAX
      and NOXA genes were observed in response to the treatment with C3 and C4, while
      cyclinD1, MMP3 and ID1 gene expression was significantly reduced. We found
      reduced invasion ability in breast cancer cells treated with C3 and C4. Taken
      together, we demonstrated that bis-salicylaldimine based dimetallic Ru-(p-cymene)
      complexes exerts anticancer effects by p53 pathway, suggesting the promising
      chemotherapeutic potentials of these Ru(II) complexes for the treatment of
      cancer. This study may further pave for their in depth in vitro or in vivo
      anticancer investigations.

PMID- 30282321
TI  - Efficient synthesis of new phenanthridine Wnt/beta-catenin signaling pathway
      agonists.
AB  - Previously, HLY78, a lycorine derivative, was identified as the first Wnt/beta
      catenin signaling agonist through binding to the DAX domain of Axin, a scaffold
      of Wnt/beta-catenin complex. In this study, to obtain more potent Wnt/beta
      catenin agonist, the structure optimization of HLY78 was carried out by design
      and synthesis of six phenanthridine derivatives, which afforded five active ones.
      In particular, 8,9-bis((1,3-dimethyl-1H-pyrazol)methoxy)-5-ethyl-4-methyl-5,6
      dihydrophenanthridine showed the most potent activity (0.15/MUM) that was
      increased nearly 30 times as that of the lead HLY78. These compounds may be
      valuable in future pharmacological or biological studies.

PMID- 30282322
TI  - Peptidomimetic growth hormone secretagogue derivatives for positron emission
      tomography imaging of the ghrelin receptor.
AB  - The ghrelin receptor is a seven-transmembrane (7-TM) receptor known to have an
      increased level of expression in human carcinoma and heart failure. Recent work
      has focused on the synthesis of positron emission tomography (PET) probes
      designed to target and image this receptor for disease diagnosis and staging.
      However, these probes have been restricted to small-molecule quinalizonones and
      peptide derivatives of the endogenous ligand ghrelin. We describe the design,
      synthesis and biological evaluation of a series of 4-fluorobenzoylated growth
      hormone secretagogues (GHSs) derived from peptidic (GHRP-1, GHPR-2 and GHRP-6)
      and peptidomimetic (G-7039, [1-Nal4]G-7039 and ipamorelin) families in order to
      test locations for the insertion of fluorine-18 for PET imaging. The
      peptidomimetic G-7039 was found to be the most suitable for 18F-radiolabelling as
      its non-radioactive 4-fluorobenzoylated analogue ([1-Nal4,Lys5(4-FB)]G-7039), had
      both a high binding affinity (IC50 = 69 nM) and promising in vitro efficacy (EC50
      = 1.1 nM). Prosthetic group radiolabelling of the precursor compound [1-Nal4]G
      7039 using N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) delivered the PET
      probe [1-Nal4,Lys5(4-[18F]-FB)]G-7039 in an average decay-corrected radiochemical
      yield of 48%, a radio-purity >= 99% and an average molar activity of >34
      GBq/MUmol. This compound could be investigated as a PET probe for the detection
      of diseases that are characterised by overexpression of the ghrelin receptor.

PMID- 30282323
TI  - Broad-spectrum antibacterial amphiphilic aminoglycosides: A new focus on the
      structure of the lipophilic groups extends the series of active dialkyl neamines.
AB  - Amphiphilic aminoglycosides (AAGs) constitute a new class of antibacterial
      compounds targeting the bacterial membranes. We have identified the 3',6-dinonyl
      neamine 9 as a broad spectrum antibacterial AAG. Here, we report on the
      synthesis, antibacterial activity and eukaryotic cytotoxicity of new 3',6-dialkyl
      neamines designed in order to finely delineate the structure-activity
      relationships relating their activity to a lipophilicity window. New broad
      spectrum antibacterial derivatives were obtained carrying two identical linear or
      branched alkyl groups or two different linear alkyl groups. Two fluorescent
      antibacterial 3',6-heterodialkyl neamines carrying a pyrenylbutyl fluorophore
      were also identified as potential tools for mechanistic study. Homodialkyl and
      heterodialkyl neamines appeared to be more active on Gram-negative bacteria than
      dinaphthylalkyl neamines. However, branched dialkyl neamines or heterodialkyl
      derivatives were found to be more cytotoxic on mammalian cells than 9. The
      exposure of P. aeruginosa over one month to half-MIC of one of the most active
      derivatives 9 demonstrated the high difficulty of resistance emergence to AAGs.

PMID- 30282324
TI  - Design, synthesis and biological evaluation of novel carbamodithioates as anti
      proliferative agents against human cancer cells.
AB  - A series of new carbamodithioates compounds has been successfully synthesized.
      All the carbamodithioate derivatives of SFE and SFA with benzenethiols
      (substituted or unsubstituted) exhibited, in general, higher percentages of
      inhibition than their parent compounds: SFE and SFA. A number of carbamodithioate
      derivatives with benzenethiols (substituted or unsubstituted) (1l, 1m, 1n, 1o,
      1q, 1s, 2l, 2n, 2p, 2q, 2r and 2s) were investigated for in vitro anti
      proliferative activities against five cancer cell lines: SMMC-7721, A549, A375,
      HCT 116 and Hela. The carbamodithioate compounds (1l, 1m, 1n, 1o, 1q and 1s)
      derived from SFE and the carbamodithioate compounds (2l, 2n, 2p, 2q, 2r and 2s)
      derived from SFA are more sensitive toward SMMC-7721and A549 cancer cells than
      toward other cancer cells in that their IC50 values are appreciably lower.
      Moreover, they exhibited stronger inhibitory activities than their parent
      compound SFE and SFE. Further investigation indicated that these carbamodithioate
      derivatives inhibited colony formation of SMMC-7721 and remarkably induced the
      G2/M or G0/G1 phase cell cycle arrest and apoptosis in SMMC-7721 cancer cells.
      More important, these carbamodithioate derivatives are stable in protic solvent
      media than their parent compounds. By virtue of the simplicity of the preparation
      of these carbamodithioate derivatives and their stability, compounds 1m and 2s
      could be the promising candidates for replacement for their parent SFE and SFA
      for cancer prevention agents.

PMID- 30282325
TI  - Fine particles exposure and cardiopulmonary morbidity in Jeddah: A time-series
      analysis.
AB  - Health effects linked to PM2.5, have been extensively studied in developed
      countries of Europe and N. America. However, little has been done in Saudi Arabia
      and the Middle East. This study evaluated the morbidity risk for cardiovascular
      (CVD) and respiratory (RD) diseases, associated with PM2.5 exposure in Jeddah,
      Saudi Arabia. 24-h PM2.5 sampling was conducted at 3 sites for 6 weeks quarterly
      from Apr 8th, 2013-Feb 18th, 2014 with simultaneous hospital data collection. The
      relative risks (RRs) for cardiopulmonary morbidity at different moving averages
      (MAs) of lagged exposures were estimated using a generalized linear time-series
      model. Elevated risks for RD were associated with recent PM2.5 exposures (0-2
      days). RD prevalence was highest in children 0-14 years. Overall, RD morbidity
      risk ranged from 1.081 (CI: 1.005-1.162) to 1.096 (CI: 1.023-1.173) at MAs_2-4;
      male, 1.081 (CI: 1.019-1.146) to 1.087 (CI: 1.020-1.159) at MAs_2-3, and female,
      1.086 (CI: 1.007-1.172) to 1.093 (CI: 1.017-1.175) at MAs_2-4. Generally, females
      0-14 years were the most at risk for RDs with RR = 1.097 (CI: 1.025-1.174) to
      1.148 (CI: 1.049-1.257). CVD morbidity risk was highest in ER visits with overall
      RR = 1.057 (CI: 1.005-1.111) to 1.137 (CI: 1.065-1.213) across all MAs; male,
      1.060 (CI: 1.007-1.204) to 1.131 (CI: 1.060-1.208); female, 1.065 (CI: 1.008
      1.125) to 1.116 (CI: 1.045-1.192). PM2.5 exposure showed significantly increased
      cardiopulmonary morbidity risk, accentuating the severe health effects associated
      with elevated PM2.5 in Jeddah. Overall, females (0-14 years) were more at risk
      for RD morbidity than males. CVD morbidity risk was relatively higher in males
      than females, with highest risk observed in age-groups above 40 years.

PMID- 30282326
TI  - New concepts on carbon redirection in wastewater treatment plants: A review.
AB  - Wastewater treatment plants (WWTPs) are no longer considered pollution removal
      systems but rather resources (nutrients and energy) recovery plants. Legislation
      imposing more stringent effluent requirements and the need energy self-sufficient
      or even energy-positive plants are the main drivers for the research and
      development of new WWTP configurations. While a lot of effort has been focused on
      developing new processes for nutrient recovery, limited efforts have been
      allocated to maximizing energy recovery from the organic load. Within this
      context, high-rate activated sludge (HRAS) is the most promising alternative
      technology to redirect carbon (organic compounds) towards energy as biogas. This
      is a critical review of the last decade's development of new alternatives for
      carbon redirection to improve the energy balance of WWTPs on both the laboratory
      and the industrial scale.

PMID- 30282327
TI  - Measuring and mapping the effectiveness of the European Air Quality Directive in
      reducing N and S deposition at the ecosystem level.
AB  - To protect human health and the environment (namely ecosystems), international
      air quality protocols and guidelines, like the Gothenburg protocol (1999) and the
      2001 EU Air Quality Directive (NECD), conveyed national emission ceilings for
      atmospheric pollutants (Directive 2001/81/EC), including the reduction of sulfur
      (S) and nitrogen (N) emissions by 2010. However, to what degree this expected
      reduction in emissions had reflections at the ecosystem level (i.e. pollutant
      levels reaching and impacting ecosystems and their organisms) remains unknown.
      Here, we used lichens as ecological indicators, together with reported air and
      precipitation pollutant concentrations, to determine and map the consequences of
      the S and N atmospheric emission's reduction, during the implementation of the
      2001 Directive (in 2002 and 2011), due primarily to the industrial-sector. The
      study area is a mixed-land-use industrialized Mediterranean agroforest ecosystem,
      in southwest Europe. The reduction of S emissions (2002-2011) was reflected at
      the ecosystem level, as the same S-declining trend was observed in atmospheric
      measurement stations and lichens alike (-70%), indicating that most S deposited
      to the ecosystem had an industrial origin. However, this was not the case for N
      with a slight N-reduction near industrial facilities, but mostly N-deposition in
      lichens increased in areas dominated by agricultural land-uses. Taken together,
      these results highlight the importance of going beyond emissions estimation and
      modeling, to assess the success of the implementation of the NECD in lowering
      pollutant accumulation in living organisms and their environment. This can only
      be achieved by measuring pollutant deposition at the ecosystem level (e.g. living
      organisms). By doing so, we were able to show that the 2001 NECD was successful
      in reducing S concentrations from Industry, whereas N remains a challenge.
      Despite the small reduction in N-emissions, deposition into ecosystems did not
      reflect these changes as agriculture and transport sectors must reduce NH3 and
      NOx emissions.

PMID- 30282328
TI  - Methyl tert-butyl ether (MtBE) in deep wells of the Patino Aquifer, Paraguay: A
      preliminary characterization.

PMID- 30282329
TI  - In vivo evaluation of porous lithium-doped hydroxyapatite scaffolds for the
      treatment of bone defect.
AB  - Hydroxyapatite (HA) possesses similar mineral components to bone and possesses
      good physicochemical properties. Even though pure HA scaffold is brittle, it is
      insufficient in promoting vascularization and osteoinductivity. This study was
      conducted to assess whether lithium (Li) incorporated into HA could improve the
      scaffolds' inherent shortcomings. In the experiments, Li-hydroxyapatite
      scaffolds' mechanical strength, biocompatibility, and biodegradability were
      researched primarily. In vivo studies, the Li hydroxyapatite scaffolds were
      implanted into an animal model to repair the bone defects. Meanwhile, we also
      evaluated the expression of angiogenic and osteogenic factors. For comparison,
      autologous bone, hydroxyapatite, and blank control groups were designed.
      According to the results, Li incorporated with hydroxyapatite did not
      significantly change the scaffold's degradation velocity, but it obtained higher
      compress mechanical strength. After Li was doped, bone regeneration was further
      enhanced but the angiogenic effect was not improved significantly. The in vivo
      study, Li-HA scaffolds improved new bone formation with GSK-3?? decreased and ??
      catenin increased. In conclusion, doped Li into hydroxyapatite was an alternative
      strategy for improving hydroxyapatite's mechanical property and promoting the
      osteogenesis potential. This method is highly recommended for clinical
      application based on this study alone.

PMID- 30282330
TI  - Mechanical loading characteristics of total hip prosthetics subjected to dynamic
      loading cycles.
AB  - The selection of best material pair in the hip prosthetics design for improved
      performance and life relies on the estimation of hip joint contact stresses and
      contact pressure distribution during various dynamic loading cycles: Climbing
      Upstairs, Climbing downstairs and Knee bending. The maximum Von Mises stress,
      contact pressure and deformation are considered factors in selecting the material
      pair in this current study. This is done by analysis of a three-dimensional
      finite element model of the acetabular component during the different dynamics
      cycles using ANSYS(r). The different material combination of bearing couples
      considered for this analysis are metal in contact with plastic, metal on metal,
      metal on ceramic, ceramic on plastic, ceramic on metal and ceramic on ceramic.
      The numerical results were validated by comparing them with the FEA results of
      Hai-Bo Jiang et al. for the existing material combinations and a high correlation
      of 92% was observed. We found that the Alumina femoral head paired with ultra
      high molecular weight polyethylene (UHMWPE) cup reduces the maximum Von Mises
      stress and maximum contact pressure developed at the interface amongst other
      material pairs.

PMID- 30282331
TI  - Optimization of the configuration of porous bone scaffolds made of
      Polyamide/Hydroxyapatite composites using Selective Laser Sintering for tissue
      engineering applications.
AB  - Numerous biomaterials are used to fabricate bone scaffolds to repair the bones
      subjected to trauma. The scaffolds are fabricated with interconnected pores with
      40-70% porosity to facilitate the entry of the cells that ensures rapid bone
      formation. In addition, the interconnected pores also serve as a channel for the
      exchange of nutrients and waste materials. Rapid prototyping techniques use the
      CAD model of the scaffold to be fabricated which facilitates fabrication of
      components with complex architecture easily. This research deals with the design,
      fabrication and analysis of porous scaffold models with different configurations.
      Apart from the conventional pore geometry like cubical, spherical shaped pores,
      their shifted arrangements were also considered for this study. The minimum pore
      size used for the study is 400 MUm and the porosity ranges from 40-70%. Based on
      the results of finite element analysis, the best scaffold configuration is
      identified and was fabricated with different build orientation using Selective
      Laser Sintering (SLS) process with different mix of Polyamide and Hydroxyapatite.
      The fabricated test specimens were evaluated based on mechanical tests for its
      strength and in vitro studies with human osteosarcoma cell line for cell growth
      studies. The mechanical tests witnesses good physical properties than the earlier
      reported research. The suitability of the porous scaffolds for bone repair is
      also ensured using finite element analysis of a human femur bone under various
      physical activities.

PMID- 30282332
TI  - The effects of NELL on corticotomy-assisted tooth movement and osteogenesis in a
      rat model.
AB  - INTRODUCTION: Exogenous Nel-like molecule type 1 (NELL1) represents a potentially
      attractive clinical treatment option in the orthodontic and other settings
      because of its osteoinductive and vasculogenic properties. AIMS: To explore
      effects of NELL1on corticotomy-assisted tooth movement and osteogenesis in a rat
      model. METHODS: Thirty Sprague-Dawley rats were divided into 6 groups: Control,
      Sham, Tooth movement only, Vehicle, NELL1-LD (low-dose NELL), NELL1-HD (high-dose
      NELL). Human recombinant NELL1 protein was applied locally (Groups NELL1-LD and
      NELL1-HD) into buccal mucosa region of left first upper molar. Then the distance
      and velocity of tooth movement was measured, animals at 6 weeks after surgery
      were sacrificed, and was followed by computed tomography and histochemical
      staining. RESULTS: Both NELL1 groups had higher bone mineral density, greater
      tooth movement distance and velocity in comparison to the Vehicle group.
      Proximally and distally, periodontal ligament width was significantly increased
      in the NELL1-LD and NELL1-HD groups. Decortication enhances remodeling, however,
      rapid bone formation by high-dose NELL1 may affect bone absorption. CONCLUSION:
      Appropriate dose of NELL1 can be administrated to reduce the total time for tooth
      movement, and may shorten the treatment time in select populations.

PMID- 30282333
TI  - Dopant-dependent tailoring of physicochemical and biological properties of
      calcium silicate bone cements.
AB  - BACKGROUND: To enhance calcium silicate cements (CSCs) towards a specific
      clinical application of endodontics and vertebroplasty, the addition of oxide
      dopants (Bi2O3, SrO, ZnO, ZrO2) as radiopacifiers allows for tailoring of
      material properties. OBJECTIVE: Effects of oxide dopants on the in vitro
      physicochemical properties and osetogenic activity of CSCs were investigated.
      METHODS: The setting time, compressive strength, radiopacity, and osteogenic
      ability of the cements were evaluated. The ability of cement samples to support
      MG63 attachment, proliferation, differentiation, and mineralization was assessed.
      RESULTS: The greater the oxide amount, the higher the setting time and
      radiopacity were in the cement. The effect of the oxide dopants on radiopacity
      followed the order Bi2O3 > ZrO2 > SrO > ZnO, which were greater than 3 mm of Al
      recommended by ISO 6876: 2001 standards. ZrO2 could reinforce compressive
      strength of the control cement, while ZnO remarkably reduced the strength. The
      adverse effect of Bi2O3 and ZrO2 was found on cell number, alkaline phosphatase
      (ALP) activity and mineralization of MG63 cells. SrO supported cell attachment,
      proliferation and differentiation, and significantly increased cellular
      mineralization compared to the control. CONCLUSIONS: The 20 wt% SrO-containing
      CSCs may be applied to endodontic treatment and vertebroplasty surgery.

PMID- 30282334
TI  - Raman spectroscopic and fractal analysis of blood samples of dengue fever
      patients.
AB  - BACKGROUND: The limitations of the existing techniques for the early detection of
      dengue fever necessitate the development of a powerful optical technique.
      OBJECTIVE: The present work is a study of Raman spectral modifications of blood
      on dengue infection and thereby to develop a spectroscopic method for its early
      detection. The images of the samples are subjected to fractal analysis to find
      the variation of fractal dimensions on dengue infection. METHODS: Correlation of
      platelet counts of dengue infected blood with Raman spectrum modification and
      fractal dimension. The effect of lowering of blood platelet count due to dengue
      infection is found to show some interesting changes in the spectrum. RESULTS: The
      full width at half maximum (FWHM) of the two bands in the region 950-1200 cm-1
      increase with the decrease of blood platelet count. The increase in fractal
      dimension gives an indication of the decrease of platelet count and hence the
      dengue infection. CONCLUSIONS: Raman spectrum and fractal analysis can
      effectively be used as potential techniques for the early detection of dengue
      infection.

PMID- 30282335
TI  - Tissue repair in neonatal and paediatric surgery: Analysis of infection in
      surgical implantation of synthetic resorbable biomaterials.
AB  - BACKGROUND: There has been increased interest in the use of biomaterials that
      resorb completely leaving only the patient's native tissue. Synthetic materials
      are advantageous for tissue repair because they are highly customisable. The
      infection rate of using resorbable natural materials in paediatric surgery has
      recently been outlined, but there has not yet been a review of the use of
      synthetic resorbable materials in paediatric surgery. OBJECTIVES: This systematic
      review analyses the risk of infection after implantation of fully resorbable
      synthetic biomaterials in paediatric cases. METHODS: The literature was searched
      from January 1970 to January 2018 (inclusive), specifically searching for
      paediatric cases (0-18 years old), use of synthetic resorbable materials and
      infection. RESULTS: The infection rate in 3573 cases of synthetic resorbable
      material implantation was 1.1% (41 cases). A Chi-squared test for independence
      found infection rate to vary among materials. Of the many biomaterials identified
      in this review, the highest infection rates were seen in Suprathel's use in burns
      injuries (12.1%). CONCLUSIONS: This review found a low infection rate in
      synthetic resorbable materials used in paediatric surgery, with particularly
      strong evidence for low infection risk in LactoSorb(r) use.

PMID- 30282336
TI  - Nonthermal control of Escherichia coli growth using extremely low frequency
      electromagnetic (ELF-EM) waves.
AB  - BACKGROUND: Escherichia coli (E. coli) bacteria normally live in the intestines
      of people and animals. Most E. coli are harmless and the treatment of the
      infection could be achieved by using antibiotics, however the effectiveness is
      still debatable and needs more investigation. OBJECTIVE: Researching the
      inhibition resonance frequency of square amplitude modulating waves (QAMW) that
      can inhibit the growth activity of E. coli and its ability to make division.
      METHODS: A range of different extremely low frequencies of square amplitude
      modulated waves (QAMW) from 0.1 to 1.0 Hz from two generators with a constant
      carrier frequency of 10 MHz, amplitude of 10 Vpp, modulating depth +/- 2 Vpp and
      constant field strength 200 V/m were used to treat E. coli cells at 37  degrees
      C. RESULTS: The exposure of E. coli to 0.3 Hz QAMW for 90 min was the most
      inhibited frequency where the bacterial growth inhibited by 42.3%. Furthermore, a
      significant increase in antibiotic susceptibility to protein and cell wall
      inhibitors was investigated. Also, results of the chromosomal DNA sequences,
      dielectric relaxation and TEM indicated highly significant molecular and
      morphological changes after the exposure. CONCLUSIONS: We concluded that the
      exposure of E. coli to QAMW at the inhibiting frequency interfered with the
      bioelectric signals generated from the bacteria during the cell division and
      changed the cellular activity and DNA sequences, and these changes lead to a
      significant inhibition of the bacterial growth. This is a new promising technique
      that aids to avoid the repetitive use of antibiotics against the bacterial
      pathogens.

PMID- 30282337
TI  - Fluid-structure interaction simulation of ureter with vesicoureteral reflux and
      primary obstructed megaureter.
AB  - Two common abnormalities in ureters include primary refluxing megaureter (PRM)
      and primary obstructed megaureter (POM). The aim of this study was to represent
      the numerical simulation of the urine flow at the end of the ureter with
      vesicoureteral reflux (VUR) and POM during peristalsis. Methodologically, the
      peristalsis in the ureter wall was created using Gaussian distribution. Fluid
      structure interaction (FSI) was applied to simulate urine-elastic wall
      interactions; and governing equations were solved using the arbitrary Lagrangian
      Eulerian method. Theories such as wall elasticity, Newtonian fluid, and
      incompressible Navier-Stokes equations were used. Velocity fields, viscous
      stresses and volumetric outflow rate profiles were obtained through the
      simulation of the ureter with VUR and POM during peristalsis. In addition, the
      effect of urine viscosity on flow rate was investigated. When the bladder
      pressure increased, VUR occurred because of the ureterovesical junction (UVJ)
      dysfunction, leading to high stresses on the wall. In the POM, the outflow rate
      was ultimately zero, and stresses on the wall were severe in the obstructed
      section. Comparing the results demonstrated that the peristalsis leads to even
      further dilation of the prestenosis portion. It was also observed that the reflux
      occurs in the ureter with VUR when the bladder pressure is high. Additionally,
      the urine velocity during the peristalsis was higher than the non-peristaltic
      ureter.

PMID- 30282338
TI  - Repeatability of small bowel transit time in capsule endoscopy in healthy
      subjects.
AB  - BACKGROUND: There are no reports to prove the repeatability of gastric transit
      time (GTT) and small bowel transit time (SBTT) in capsule endoscopy (CE).
      OBJECTIVE: To clarify the repeatability and factors that affect GTT/SBTT in CE.
      METHODS: We analyzed the data of 150 healthy subjects from our previous
      randomized controlled trial that compared small intestinal injuries between two
      14-day treatment groups: 1) celecoxib and 2) loxoprofen + lansoprazole.
      Correlation of GTT/SBTT with pre- and post-treatment CE was analyzed. In
      addition, the associations of pre-treatment CE SBTT with physical factors, post
      treatment CE SBTT and the presence of small intestinal mucosal injuries were
      analyzed. RESULTS: Analyses of 148 subjects pre-treatment CE and 146 subjects
      post-treatment CE were performed. There were no significant differences between
      mean GTT and SBTT before and after treatment. Both GTT (?? = 0.22, p < 0.01) and
      SBTT (?? = 0.47, p < 0.0001) showed positive correlations between pre- and post
      treatment CE. In pre-treatment CE, physical factors and the presence of small
      intestinal mucosal injury had no associations with SBTT. CONCLUSIONS: Moderate
      correlation in SBTT and slight correlation in GTT were shown on repeated CE. The
      factors affecting SBTT were not clarified in this analysis.

PMID- 30282339
TI  - Patient-specific design for articular surface conformity to preserve normal knee
      mechanics in posterior stabilized total knee arthroplasty.
AB  - BACKGROUND: Contemporary total knee arthroplasty (TKA) provides remarkable
      clinical benefits. However, the normal function of the knee is not fully
      restored. Recent improvements in imaging and manufacturing have utilized the
      development of customized design to fit the unique shape of individual patients.
      OBJECTIVE: The purpose of the present study is to investigate the preservation of
      normal knee biomechanics by using specific articular surface conformity in
      customized posterior stabilized (PS)-TKA. METHODS: This includes customized PS
      TKA, PS-TKA with conforming conformity (CPS-TKA), medial pivot conformity with PS
      TKA (MPS-TKA), and PS-TKA with mimetic anatomy femoral and tibial articular
      surface (APS-TKA). In this study, kinematics, collateral ligament force and
      quadriceps force were evaluated using a computational simulation under a deep
      knee bend condition. RESULTS: A conventional TKA did not provide the normal
      internal tibial rotation with flexion leading to abnormal femoral rollback. The
      APS-TKA exhibited normal-like femoral rollback kinematics but did not exhibit
      normal internal tibial rotation. However, APS-TKA exhibited the most normal-like
      collateral ligament and quadriceps forces. CONCLUSIONS: Although the APS-TKA
      exhibited more normal-like biomechanics, it did not restore normal knee
      biomechanics owing to the absence of the cruciate ligament and post-cam
      mechanism.

PMID- 30282340
TI  - Mechanical properties of cancellous tissue in compression test and
      nanoindentation.
AB  - The goal of the study was to determine material constants of cancellous tissue in
      a compression test taking into account stress-strain characteristics. The
      nineteen test samples were resected from a femoral head of a patient qualified
      for a hip replacement surgery. During the compression tests, load-displacement
      curves were evaluated and stress-strain characteristics (??-??) of the cancellous
      bone tissue were calculated. A special one-touch extensometer was used. The use
      of an extensometer improves the displacement measurement accuracy with respect to
      the measurement using standard crosshead. The obtained values of the mechanical
      parameters as well as the stress-strain curves are the basis for further research
      going into the development of bone tissue constitutive equations.

PMID- 30282341
TI  - Magnesium doping on TiN coatings affects mesenchymal stem cell differentiation
      and proliferation positively in a dose-dependent manner.
AB  - BACKGROUND: In vitro evaluation of cell-surface interactions for hard tissue
      implants have mostly been done using osteoblasts. However, when an implant is
      placed in the body, mesenchymal stem cells (MSCs) play a major role in new bone
      formation. Therefore, using MSCs in cell-surface investigations may provide more
      reliable information on the prediction of in vivo behavior of implants.
      OBJECTIVE: In this study, Mg doped TiN coatings ((Ti,Mg)N) were prepared and
      tested for their effect on MSC differentiation and mineralization. METHODS: MSCs
      were isolated from rat bone marrow (rBMSCs) and seeded onto bare Ti, TiN and Mg
      containing (Ti,Mg)N surfaces. Cell proliferation, osteogenic differentiation
      (collagen type 1, alkaline phosphatase activity), calcium phosphate deposition
      (von Kossa staining, Scanning Electron Microscopy) analysis were conducted.
      RESULTS: Differentiation towards osteoblast lineage was significantly improved
      with the increment in Mg presence. Collagen type I deposition, mineralization,
      and the ALP activity were higher on high Mg containing (>10 at% Mg) surfaces but
      differentiation of rBMSCs were found to be delayed. CONCLUSIONS: Mg presence
      affected rBMSCs proliferation and differentiation positively in a dose-dependent
      manner. However, high Mg amounts delayed both proliferation and differentiation.

PMID- 30282343
TI  - Review of core-multishell nanostructured models for nano-biomedical and nano
      biopharmaceutical application.
AB  - The main advantage of a theoretical approach is essential knowledge of the
      mechanisms that allow us to comprehend the experimental conditions that we have
      to fulfill to be able to get the desired results. Based on our research in
      ultrathin crystal structures performed so far, superlattices, Q-wires and Q-dots,
      we will consider the materials that can act as carriers for medicines and tagged
      substances. For this purpose we established a shell-model of ultrathin crystals
      and investigated their fundamental characteristics. This could be considered as a
      form of nano-engineering. In this paper we will analyze application of
      nanomaterials in biomedicine, that is to say we will present the recent
      accomplishments in basic and clinical nanomedicine. Achieving full potential of
      nanomedicine may be years or even decades away, however, potential advances in
      drug delivery, diagnosis, and development of nanotechnology-related drugs start
      to change the landscape of medicine. Site-specific targeted drug delivery (made
      possible by the availability of unique delivery platforms, such as dendrimers,
      nanoparticles and nanoliposomes) and personalized medicines (result of the
      advance in pharmacogenetics) are just a few concepts on the horizon of research.
      In this paper, especially, we have analyzed the changes in basic physical
      properties of spherical-shaped nanoparticles that can be made in several
      (nano)layers and have, at the same time, multiple applications in medicine. This
      paper presents a review of our current achievement in the field of theoretical
      physics of ultrathin films and possible ways to materialize the same in the field
      of nanopharmacy.

PMID- 30282342
TI  - Evaluation of swelling processes of various natural polymer matrix tablets by X
      ray computed tomography and controlled drug release.
AB  - BACKGROUND: The swelling properties and the drug-release sustainability of pre
      gelatinized starches (??-starch) tablets depend on the polymer characteristics.
      OBJECTBS: In order to clarify the drug release form, the natural polymers (NPs)
      were investigated. The relationship between drug release and swelling of natural
      polymers (NPs), the swelling processes of various starch polymers, were
      investigated using a drug-release test (DRT) and X-ray computed tomography (XCT).
      NPs consisting of various starches such as glutinous rice starch (GRS), corn
      starch (CS), and tapioca starch (TS) were used as additives for sustained drug
      release tablets. Tablets consisted of 5% theophylline, 94% ??-starch, and 1%
      magnesium stearate and were compressed at 6 kN. DRTs were measured in distilled
      water at 37  degrees C, and the drug concentrations were measured using UV (271
      nm). Swelling ratio (R) profiles of the tablets during DRTs were evaluated based
      on XCT images. RESULTS: The order of the drug-release rate constant of the
      tablets was TS < GRS < CS. XCT images of the tablets were measured during the
      DRTs, and CS, GRS, and TS tablets swelled and showed increased gel-layers, and
      then finally disintegrated at 6, 9, and 11 h, respectively. CONCLUSION: The
      relationship between R profile and the % drug release of the tablets differed
      depending on the kind of NP used.

PMID- 30282344
TI  - A finite element analysis for monitoring the healing progression of fixator-bone
      system under three loading conditions.
AB  - BACKGROUND: Unilateral external fixators are widely used in orthopedics to
      stabilize fractured bones and in the treatment of limb deformities. The main
      value for evaluation of mechanical stability of the external fixator is fixator
      stiffness. The fixator stiffness is an important factor as it will influence the
      biomechanical environment to which fixator and regenerating tissues are exposed.
      OBJECTIVE: The main objective of this work was to monitor the transmission of
      stress and the change of displacement generated in fixator-bone system under
      three loading conditions during healing process. METHODS: In this study, a finite
      element model with changing Young's modulus of the callus is established, finite
      element analysis was used to investigating stress and deformation of fixator-bone
      system caused by axial load, torsional load and bending load during three healing
      stages. RESULTS: The results reveal that at different healing stages, stress
      distribution between the fixator and fractured bone is different, the position of
      displacement is mainly concentrated in the fracture site and proximal bone and
      with the increase of healing time, the deformation decreased. CONCLUSIONS: This
      work helps orthopedic doctors to monitor the progression of fracture healing and
      determine the appropriate time for removal of a fixation device and provide
      useful information.

PMID- 30282345
TI  - Biomechanical evaluation of four surgical scenarios of lumbar fusion with
      hyperlordotic interbody cage: A finite element study.
AB  - BACKGROUND: Lumbar spinal fusion in the interbody space is augmented with
      interbody fusion cages to provide structural support while arthrodesis occurs.
      Subsidence is a serious complication of interbody fusion. However, the
      biomechanical influence of anterior longitudinal ligament (ALL) and pedicle
      screws on subsidence has not been fully understood. OBJECTIVE: To investigate
      biomechanical effects of the hyperlordotic cages in different surgical conditions
      using finite element analysis. METHODS: Four surgical finite element (FE) models
      were constructed by inserting 15 degree lordosis cage at the L3-L4 disc space.
      The four surgical conditions were ALL intact (M1), ALL resected (M2), ALL intact
      and bilateral pedicle screws (M3), and ALL resected and bilateral pedicle screws
      (M4). Follow loads were applied at the L2 vertebral body while the inferior
      surface of L5 was fixed. FEA was implemented to simulate the four motion modes
      and biomechanical properties of four fusion scenarios with hyperlordotic
      interbody cage were compared. RESULTS: The range of motion (ROM) and facet joint
      force (FJF) at L3-L4 decreased significantly after fusion during all the motion
      modes. The cage stress and endplate stress at L3-L4 increased significantly after
      fusion during all the motion modes. The cage stress and endplate stress at L3-L4
      for M3 and M4 were smaller than that for M1 and M2 during all the motion modes.
      The FJF at L3-L4 for M3 and M4 were smaller than that for M1 and M2 during
      extension, bending, and rotation. CONCLUSIONS: ALL has little effect on the
      biomechanics after lumbar fusion with hyperlordotic interbody cage. The bilateral
      pedicle screws significantly decreased the stress in cage, stress in endplate at
      L3-L4, and lowered facet contact force except for flexion mode. The implication
      is that the supplemental bilateral pedicle screws are recommended whether or not
      the ALL is resected.

PMID- 30282346
TI  - Dynamic response and material sensitivity analysis of pelvic complex numerical
      model under side impact.
AB  - BACKGROUND: The surrogate design and clinical diagnostic suggest that the pelvic
      dynamic response should be the basis of bone fracture mechanism study under side
      impact. Pelvic response indicators are the impact force, compression (C), viscous
      criterion (VC), bone stress, and bone strain. However, no evaluation of these
      indicators has been conducted. OBJECTIVE: To evaluate pelvic response indicators
      under side impact. METHODS: A sitting pelvic finite element (FE) complex model
      comprising bone, artery, ligaments, and soft tissue was constructed. The dynamic
      response of the model under side impact with initial velocity of 3 m/s was
      investigated and material sensitivity analysis was complemented by changing bone
      elastic modulus. RESULTS: The pelvic FE model could predict response under side
      impact. Specifically, the indicators such as artery pressure and strain, together
      with the ligaments axial force and strain were provided. The sensitivity analysis
      showed the impact force, bone stress, and axial force were sensitive to the
      elastic modulus, whereas, C, VC, bone strain, and artery pressure were not.
      CONCLUSIONS: The sitting FE model in this study can predict pelvic dynamic
      response, and C, VC, bone strain and artery pressure are proposed for pelvic
      tolerance instead of impact force under side impact.

PMID- 30282347
TI  - Influence of different implant-abutment connections on stress distribution in
      single tilted implants and peripheral bone: A three-dimensional finite element
      analysis.
AB  - BACKGROUND: The load transfer between the implant-bone interface depends on
      various factors, including loading type; material properties of the implant and
      prosthesis; and implant geometry, length, diameter, and shape. OBJECTIVE: The
      purpose of this study was to evaluate stress distribution in single tilted bone
      level implants with different connections and peripheral bone under vertical and
      oblique loads using three-dimensional (3D) finite element analysis
      (FEA).METHOS.3D models of four different implant systems and their abutments were
      created from the data (computer-aided design) of original implants and abutments
      scanned with an optical scanner. The implants were placed in the bone block at
      degrees of 0 degrees , 15 degrees , and 30 degrees . Then, a 3D model of the
      metal-ceramic crown was created and a 100-N total load was applied vertically and
      obliquely. RESULTS: Stress analyses showed variable results depending on the
      connection design and tilting angle; however, the tube in tube (TIT) connection
      type exhibited lower stress values in most loading and tilting simulations.
      CONCLUSIONS: Increase in tilting angle showed variable results in each connection
      design. The TIT connection design was found to be more successful in terms of
      stress distributions in the implant components and the peripheral bone.

PMID- 30282348
TI  - Regional pulse wave velocity and stress in aneurysmal arch-shaped aorta.
AB  - The pulse wave velocity (PWV) has been shown to be associated with the properties
      of blood vessel and a cardiovascular risk factor such as aneurysm. The global PWV
      estimation is applied in conventional clinical diagnosis. However, the geometry
      of blood vessel changes along the wave traveling path and the global PWV
      estimation may not always detect regional wall changes resulting from
      cardiovascular diseases. In this study, a fluid structure interaction (FSI)
      analysis was applied on arch-shaped aortas with and without aneurysm aimed at
      determining the effects of the number of aneurysm, aneurysm size and the modulus
      ratio (aneurysm to wall modulus) on the pulse wave propagation and velocity. The
      characterization for each stage of aneurysmal aorta was simulated by
      progressively increasing aortic stiffness and aneurysm size. The pulse wave
      propagations and velocities were estimated from the two-dimensional spatial
      temporal plot of the normalized wall displacement based on elastic deformation.
      The descending forward and arch reflected PWVs of aneurysmal aortic arch models
      were found up to 9.7% and 122.8%, respectively, deviate from the PWV of non
      aneurysmal aortic arch model. The PWV patterns and magnitudes can be used to
      distinguish the characterization of the normal and aneurysmal aortic walls and
      shown to be relevant regional markers utilized in clinical diagnosis.

PMID- 30282349
TI  - Effect of core stability exercises on postpartum lumbopelvic pain: A randomized
      controlled trial.
AB  - BACKGROUND: Core stability exercises have been widely advocated for management of
      patients with different musculoskeletal conditions, even though its effect on
      postpartum lumbopelvic pain (LPP) has not been fully investigated. OBJECTIVE:
      This study was conducted to investigate the effect of core stability exercises on
      postpartum LPP. METHODS: Thirty four women suffering from postpartum LPP were
      randomly assigned to the study or control group. The control group (n= 17)
      received infrared radiation and continuous ultrasound on lumbosacral region (L1
      S5), whereas the study group (n= 17) received core stability exercises in
      addition to infrared radiation and continuous ultrasound three sessions a week
      for six weeks. Pain Pressure Threshold (PPT), Visual Analogue Scale (VAS) and
      Oswestry Disability Index (ODI) were assessed for all participants in both groups
      before and after the treatment program. RESULTS: There was a significant
      improvement in PPT, VAS and ODI post-treatment compared with the pre-treatment in
      both groups (p= 0.001). There was a significant improvement in participants who
      received core stability exercises as compared to participants treated with the
      traditional treatment in PPT (P= 0.001), VAS (P= 0.001) and ODI (P= 0.009).
      CONCLUSIONS: Core stability exercises in addition to conventional treatment
      significantly decreased pain and improved function for women with postpartum LPP.

PMID- 30282350
TI  - Production and characterization of monoclonal antibodies against recombinant
      extracellular domain of CD99.
AB  - BACKGROUND AND OBJECTIVE: CD99/MIC2gene product is a heavily glycosylated
      transmembrane protein which plays a major role in homotypic cell adhesion,
      apoptosis of double positive T cells and vesicular protein trafficking. It is
      over expressed in various cancers and has been considered as an ideal therapeutic
      target. The present study focused at developing monoclonal antibodies against the
      extracellular domain (ECD) of CD99 using hybridoma technology. MATERIALS AND
      METHODS: In order to generate monoclonal antibodies, the recombinant ECD of CD99
      was used for immunizing the mice. Resulting hybridomas were screened through
      indirect ELISA. Clones which gave high absorbance values were sub cloned by
      limiting dilution followed by isotype determination, IP, WB and FACS. The
      monoclonal antibody 547F2 4F12 was purified from culture supernatant using FPLC
      and further screened using IF. Finally, the antibodies were validated for
      specificity using siRNA knock-down. RESULTS: We were able to establish stable
      hybridoma clones secreting CD99 antibodies. The antibodies reacted with both the
      recombinant ECD as well as the wild type CD99 and their isotype's were determined
      as IgM. CONCLUSION: Based on these results, we propose that the purified
      monoclonal antibody 547F2 4F12 could be possibly used for targeting tumors which
      over express CD99.

PMID- 30282351
TI  - Visual Processing of Emotional Faces is Preserved in Mild Cognitive Impairment.
AB  - BACKGROUND: Research suggests that deficits in emotion recognition are evident in
      individuals with amnestic mild cognitive impairment (aMCI), a group 'at risk' of
      developing dementia. The mechanisms underlying this deficit, however, are
      unclear. OBJECTIVE: In this study, we sought to determine whether there are
      alterations in the way in which individuals with MCI visually explore emotional
      facial stimuli. METHODS: Eighteen healthy older controls (mean age = 64.6 years)
      and 32 individuals with MCI were recruited including 18 with the non-amnestic
      multiple domain (naMCI-md) subtype (mean age = 63.8 years) and 14 with the
      amnestic multiple domain (aMCI-md) subtype (mean age = 67.9 years). All
      participants were given a novel eye-tracking paradigm to investigate eye gaze
      while viewing images of emotional faces on a computer screen. RESULTS: Analyses
      of eye gaze revealed no significant difference in the percentage of time that
      groups spent fixating on facial and peripheral facial regions when viewing
      emotional faces. All participants showed a relative preference for the eye region
      of faces relative to all other regions. Individuals with aMCI-md were found to be
      less accurate than controls and naMCI-md on emotion recognition measures. For
      naMCI-md individuals, significant relationships were found between efficiencies
      in visual scanning and increased fixation time on the eye region. CONCLUSIONS:
      Visual processing strategies adopted by aMCI-md individuals when exploring
      emotional faces do not significantly differ from those of healthy controls or
      naMCI-md individuals. This suggests that impaired facial emotion recognition in
      aMCI-md is not likely accounted for by visual processing differences, but rather
      may reflect an eroded ability to extract meaningful cues from the eye region.

PMID- 30282352
TI  - Parietal Involvement in the Semantic Variant of Primary Progressive Aphasia with
      Alzheimer's Disease Cerebrospinal Fluid Profile.
AB  - Semantic variant of primary progressive aphasia (svPPA) is typically associated
      with non-Alzheimer's disease (AD) pathology. However, some anatomopathological
      studies have found AD lesions in those patients. We compared brain perfusion
      SPECT of 18 svPPA patients with cerebrospinal fluid (CSF) biomarkers indicative
      of non-AD pathology (svPPA-nonAD) and three svPPA patients with CSF biomarkers
      indicative of underlying AD (svPPA-AD). All svPPA patients had severe left
      temporopolar hypoperfusion. SvPPA-nonAD had additional anterior cingulate and
      mediofrontal hypoperfusion, whereas svPPA-AD had greater left parietal and
      posterior cingulate involvement. Parietal damage in svPPA constitutes a biomarker
      for underlying Alzheimer pathology thus refining the classification of this PPA
      variant.

PMID- 30282353
TI  - Microglia CREB-Phosphorylation Mediates Amyloid-beta-Induced Neuronal Toxicity.
AB  - Extracellular accumulation of amyloid-beta (Abeta) forming senile plaques is one
      of the hallmark pathologies in Alzheimer's disease (AD), while the mechanisms
      underlying the neuronal toxic effect of Abeta are not fully understood. Here, we
      found that intracerebroventricular infusion of the aged Abeta42 in mice only
      induces memory deficit at 24 h but not at 7 days. Interestingly, a remarkably
      increased CREB (cAMP response element-binding protein) Ser133-phosphorylation
      (pS133-CREB) with microglial activation was detected at 24 h but not at 7 days
      after Abeta infusion. Abeta treatment for 24 h increased pS133-CREB level in
      microglia of the hippocampal non-granular cell layers with remarkably decreased
      pS133-CREB immunoreactivity in neurons of the hippocampal granular cell layers,
      including CA1, CA3, and DG subsets. Inhibition of microglia activation by
      minocycline or CREB phosphorylation by H89, an inhibitor of protein kinase A
      (PKA), abolished Abeta-induced microglia CREB hyperphosphorylation with
      restoration of neuronal function and attenuation of inflammatory response, i.e.,
      reduced levels of interleukin-6 (IL6) and pCREB binding of matrix
      metalloproteinase-9 (MMP9) DNA. Finally, treatment of the primary hippocampal
      neurons with Abeta-potentiated microglia media decreased neuronal GluN1 and GluA2
      levels, while simultaneous inhibition of PKA restored the levels. These novel
      findings reveal that intracerebroventricular infusion of Abeta only induces
      transient memory deficit in mice and the molecular mechanisms involve a
      stimulated microglial CREB phosphorylation.

PMID- 30282354
TI  - Possible Role of Chitin-Like Proteins in the Etiology of Alzheimer's Disease.
AB  - Chitin is a beta-linked straight chain carbohydrate matrix monopolymer prominent
      in invertebrates, from fungi to arthropods. Surprisingly, chitin is now
      documented in vertebrates, including humans, a component of vertebrate physiology
      that has been neglected until now. Chitin levels are elevated in Alzheimer's
      disease (AD) patients, not only in the central nervous system but also in the
      cerebrospinal fluid and plasma. Elevated levels of chitin lectin have been
      reported in patients with AD. Chitinase activity varies widely in the human
      population. Chitin levels can increase in individuals with intrinsically low
      chitinase activity. Elevated amounts of chitin can reflect accumulation of the
      small chitin fragments that remain wherever rapid hyaluronan synthesis occurs.
      Another source of chitin may be from remote fungal infections. Chitin can be
      toxic for neurons, and its accumulation may lead to the development of AD. We
      present new suggestions for animal models and treatment modalities that could
      prove useful in future research endeavors. An unexpected connection with
      Gaucher's disease patients and their heterozygote relatives is also identified.
      These chitin-related mechanisms are novel approaches to AD whose etiology until
      now has defied explication.

PMID- 30282355
TI  - Effect of Physical Activity on the Progression of Alzheimer's Disease: The
      Clinical Research Center for Dementia of South Korea Study.
AB  - BACKGROUND: There is a lack of research on the effects of physical activity (PA)
      on the progression of Alzheimer's disease (AD). OBJECTIVES: We investigated
      whether PA is associated with progression of dementia and mortality in AD.
      METHODS: In the present study, 934 patients with mild-to-moderate AD were
      included. PA was evaluated using a questionnaire written by the caregiver. The
      outcome measures were the Clinical Dementia Rating-Sum of Boxes (CDR-SB), Seoul
      Instrumental Activities of Daily Living (S-IADL), Caregiver-Administered
      Neuropsychiatric Inventory (CGA-NPI), a global composite score of
      neuropsychological subtests, and mortality. They were evaluated annually and
      received a maximum of three follow-up examinations. RESULTS: Between-group
      differences compared with the no PA group in the change of CDR-SB scores were 
      0.431 (95% CI = -0.824~-0.039; p = 0.031) for the moderate PA group (150-750
      minutes per week of moderate intensity PA), and -1.148 (-1.656~-0.639; p < 0.001)
      for the high PA group (>750 minutes per week). As PA increased, there was a
      significant trend to slow the rate of increase in the CDR-SB, S-IADL, and CGA-NPI
      scores. The patients with >=150 minutes per week for each of non-recreational and
      recreational PAs had a lower risk of mortality compared to those with <150
      minutes per week for each of the PAs (hazard ratio 0.22, 95% CI = 0.05~0.88; p =
      0.033). CONCLUSION: More PA is associated with slower progression of dementia
      severity, functional decline, and abnormal behavior, and with a lower risk of
      mortality in AD.

PMID- 30282356
TI  - Subjective Cognitive Decline Prediction of Mortality: Results from the Einstein
      Aging Study.
AB  - BACKGROUND: The relation of pre-dementia stages to mortality has not been fully
      explored. Previous work examining subjective cognitive decline (SCD) and
      mortality is limited and mixed regarding methods used and consistency of
      findings. OBJECTIVE: To examine SCD and mortality in a longitudinal, community
      based cohort, using item response theory (IRT) methodology to form a composite
      SCD measure. Also, to assess whether this relationship was independent of
      clinical cognitive status. METHODS: The Einstein Aging Study is a diverse
      longitudinal cohort of adults aged >=70. SCD items were extracted from baseline
      CERAD questionnaires and a composite score was formed using IRT methodology. A
      total of 1,741 participants with complete data were clinically diagnosed as
      cognitively normal, or as having amnestic mild cognitive impairment (aMCI),
      nonamnestic mild cognitive impairment (naMCI), or dementia. 645 deaths occurred
      over a period of 8,912 person-years of follow-up. Cox proportional hazard models
      predicted time to death adjusting for covariates. RESULTS: A one standard
      deviation unit increase in level of SCD was associated with >20% higher risk of
      mortality. However, when models were adjusted for clinical cognitive status, the
      association was no longer significant. Both dementia and aMCI predicted
      mortality. Furthermore, when analyses focused only on those without cognitive
      impairment, SCD level did not predict mortality. CONCLUSIONS: The association of
      SCD with mortality may be due to the association of SCD with clinical cognitive
      status. Thus, SCD may be used as a community-based screen to initially identify
      those with cognitive impairment who may be at greatest risk for death.

PMID- 30282357
TI  - Learning Processes and Brain Connectivity in A Cognitive-Motor Task in
      Neurodegeneration: Evidence from EEG Network Analysis.
AB  - Electroencephalographic (EEG) rhythms are linked to any kind of learning and
      cognitive performance including motor tasks. The brain is a complex network
      consisting of spatially distributed networks dedicated to different functions
      including cognitive domains where dynamic interactions of several brain areas
      play a pivotal role. Brain connectome could be a useful approach not only to
      mechanisms underlying brain cognitive functions, but also to those supporting
      different mental states. This goal was approached via a learning task providing
      the possibility to predict performance and learning along physiological and
      pathological brain aging. Eighty-six subjects (22 healthy, 47 amnesic mild
      cognitive impairment, 17 Alzheimer's disease) were recruited reflecting the whole
      spectrum of normal and abnormal brain connectivity scenarios. EEG recordings were
      performed at rest, with closed eyes, both before and after the task (Sensory
      Motor Learning task consisting of a visual rotation paradigm). Brain network
      properties were described by Small World index (SW), representing a combination
      of segregation and integration properties. Correlation analyses showed that alpha
      2 SW in pre-task significantly predict learning (r  =  -0.2592, p < 0.0342):
      lower alpha 2 SW (higher possibility to increase during task and better the
      learning of this task), higher the learning as measured by the number of reached
      targets. These results suggest that, by means of an innovative analysis applied
      to a low-cost and widely available techniques (SW applied to EEG), the functional
      connectome approach as well as conventional biomarkers would be effective methods
      for monitoring learning progress during training both in normal and abnormal
      conditions.

PMID- 30282358
TI  - Amyloid and FDG PET of Successful Cognitive Aging: Global and Cingulate-Specific
      Differences.
AB  - BACKGROUND: Some individuals, called Supernormals (SN), maintain excellent memory
      in old age. While brain structural and functional integrity in SN seem to be
      aging-resistant, their amyloidosis and neural injury status has not been well
      studied. OBJECTIVE: The goal of this study was to compare cortical amyloid
      deposition and glucose metabolism between SN and older adults with normal
      cognition (NC), amnestic mild cognitive impairment (MCI), and Alzheimer's disease
      (AD). METHODS: Subjects from the ADNI database were included if they received T1
      weighted MRI, amyloid PET, FDG-PET, and cognitive testing within a 6-month
      period, yielding 27 AD, 69 MCI, 172 NC, and 122 SN. PET standardized uptake value
      ratios (SUVrs) were calculated for the whole cortex and 68 regions of interest,
      with whole cerebellum serving as reference. RESULTS: SN had lower whole cortex
      amyloid than MCI, and higher glucose metabolism than all others. Regional
      analysis revealed that amyloid burden and glucose metabolism in the right isthmus
      cingulate cortex differed in SN compared to others, while SN glucose metabolism
      also differed from others in several frontal and temporal regions. CONCLUSION:
      Preserved cortical glucose metabolism, and lower levels of amyloidosis and
      glucose hypometabolism in the right isthmus cingulate cortex, contributes to the
      Supernormal phenomenon. These findings may be informative for development of
      early screening biomarkers and therapeutic targets for modification of cognitive
      trajectories.

PMID- 30282359
TI  - Brain Amyloid Contribution to Cognitive Dysfunction in Early-Stage Parkinson's
      Disease: The PPMI Dataset.
AB  - BACKGROUND: The pathological processes underlying cognitive impairment in
      Parkinson's disease (PD) are heterogeneous and the contribution of cerebral
      amyloid deposits is poorly defined, particularly in the early stages of the
      disease. OBJECTIVE: To investigate regional [18F]florbetaben binding to amyloid
      beta (Abeta) and its contribution to cognitive dysfunction in early stage PD.
      METHODS: A multicenter cohort of 48 PD patients from the Parkinson's Progression
      Marker Initiative (PPMI) underwent [18F]florbetaben positron emission tomography
      (PET) scanning. Clinical features, including demographic characteristics, motor
      severity, cerebrospinal fluid (CSF), and cognitive testing were systematically
      assessed according to the PPMI study protocol. For the purpose of this study, we
      analyzed various neuropsychological tests assessing all cognitive functions.
      RESULTS: There were 10/48 (21%) amyloid positive PD patients (PDAbeta+).
      Increased [18F]florbetaben uptake in widespread cortical and subcortical regions
      was associated with poorer performance on global cognition, as assessed by
      Montreal Cognitive Assessment (MoCA), and impaired performance on Symbol Digit
      Modality test (SDMT). Further, we found that PDAbeta+ patients had higher CSF
      total-tau/Abeta1 - 42 (p = 0.001) and phosphorylated-tau/Abeta1 - 42 in (p =
      0.002) compared to amyloid-negative PD. CONCLUSION: These findings suggest that
      multiple disease processes are associated with PD cognitive impairment and
      amyloid deposits may be observed already in early stages. However, prevalence of
      amyloid positivity is in the range of literature age-matched control population.
      Increased cortical and subcortical amyloid is associated with poor performance in
      attentive-executive domains while cognitive deficits at MoCA and SDMT may
      identify amyloid-related dysfunction in early PD.

PMID- 30282360
TI  - Neuroprotective Effects of Amylin Analogues on Alzheimer's Disease Pathogenesis
      and Cognition.
AB  - Type II diabetes (T2D) has been identified as a major risk factor for the
      development of Alzheimer's disease (AD). Interestingly, both AD and T2D have
      similar characteristics including amyloid peptide aggregation, decreased
      metabolism, and increased oxidative stress and inflammation. Despite their
      prevalence, therapies for these diseases are limited. To date, most therapies for
      AD have targeted amyloid-beta or tau. Unfortunately, most of these clinical
      trials have been largely unsuccessful, creating a crucial need for novel
      therapies. A number of studies have shown that metabolic hormone therapies are
      effective at ameliorating high blood glucose levels in diabetics as well as
      improving cognitive function in AD and mild cognitive impairment patients.
      Pramlintide, a synthetic analogue of the pancreatic hormone amylin, has been
      developed and used for years now as a treatment for both type I diabetes and T2D
      due to the loss of beta-islet cells responsible for producing amylin.
      Importantly, recent data demonstrates its potential therapeutic role for AD as
      well. This review aims at addressing parallels between T2D and AD at a
      pathological and functional level, focusing on amylin signaling as a key,
      overlapping mediator in both diseases. The potential therapeutic use of this
      hormone to treat AD will also be explored from a mechanistic viewpoint.

PMID- 30282361
TI  - Aortic Stiffness is Associated with Increased Risk of Incident Dementia in Older
      Adults.
AB  - Cardiovascular disease risk factors, including age, hypertension, and diabetes,
      contribute to aortic stiffness and subclinical cardiovascular and brain disease,
      increasing dementia risk. Aortic stiffness, measured by carotid-femoral pulse
      wave velocity (cfPWV), reduces the buffering of pulsatile blood flow, exposing
      cerebral small arteries to microvascular damage. High cfPWV is related to white
      matter hyperintensities and brain amyloid deposition, and to cognitive decline,
      but it is unclear whether cfPWV independently predicts incident dementia.
      Therefore, we tested the hypothesis that cfPWV predicts incident dementia in
      older adults, independent of potential confounders. The Cardiovascular Health
      Study Cognition Study followed 532 non-demented older adults with annual
      cognitive exams from 1998-99 through 2013. CfPWV was measured on 356 (mean age =
      78, 59% women) between 1996-2000. Over 15 years, 212 (59.6%) developed dementia
      (median time from cfPWV measurement = 4 years). In age and sex-adjusted Cox
      models, cfPWV was significantly associated with increased risk of dementia, but
      systolic blood pressure, mean arterial pressure and pulse pressure were not.
      CfPWV (transformed as - 1/cfPWV) remained significantly associated with dementia
      risk when further adjusted for education, race, APOEE4, diabetes, body mass
      index, mean arterial pressure, and anti-hypertensive medication (hazard ratio =
      1.60, 95% CI = 1.02, 2.51). Results were similar when further adjusted for
      baseline global cognition, subclinical brain measures, and coronary artery
      calcification. Finally, higher cfPWV was related to lower physical activity
      intensity and higher systolic blood pressure, heart rate, and waist circumference
      measured 5 years prior. An important unanswered question is whether interventions
      to slow arterial stiffening can reduce the risk of dementia.

PMID- 30282363
TI  - Frontotemporal Dementia Misdiagnosed for Post-Treatment Lyme Disease Syndrome or
      vice versa? A Treviso Dementia (TREDEM) Registry Case Report.
AB  - We describe the case of a 61-year-old woman diagnosed with Borreliosis at the age
      of 57. Subsequently, the patient developed depression, anxiety, and behavioral
      disturbances. A lumbar puncture excluded the condition of Neuroborreliosis. The
      diagnostic workup included: an MRI scan, a 18F-FDG PET, a 123I-ioflupane-SPECT,
      an amyloid-beta PET, a specific genetic analysis, and a neuropsychological
      evaluation. Based on our investigation, the patient was diagnosed with probable
      behavioral-frontotemporal dementia (bvFTD), whereas in the previous years, the
      patient had been considered firstly as a case of Post-Treatment-Lyme Disease and,
      secondly, a psychiatric patient. We believe that, in the present case, such
      initial symptoms of Borrelia infection may have superimposed on those of bvFTD
      rather than playing as a contributory cause.

PMID- 30282362
TI  - Neurotoxic Effects of Abeta6-42 Peptides Mimicking Putative Products Formed by
      the Angiotensin Converting Enzyme.
AB  - Angiotensin converting enzyme (ACE) is involved in proteolytic processing of the
      amyloid-beta(Abeta) peptide implicated in the development of Alzheimer's disease
      (AD) and known products of ACE-based processing of Abeta42 are characterized by
      reduced aggregability and cytotoxicity. Recently it has been demonstrated that
      ACE can act as an arginine specific endopeptidase cleaving the N-terminal
      pentapeptide (Abeta1-5) from synthetic Abeta peptide analogues. In the context of
      proteolytic processing of full length Abeta42, this suggests possible formation
      of Abeta6-42 species. The aim of this study was to test a hypothesis that some N
      terminally truncated Abeta peptide(s) could retain aggregability and neurotoxic
      properties typical for Abeta42. We have investigated aggregability of two amyloid
      beta peptides, Abeta6-42 and isoD7-Abeta6-42, mimicking potential proteolytic
      products of Abeta42 and isoD7-Abeta42, and evaluated their effects on the
      repertoire of brain Abeta binding proteins, and cytotoxicity towards
      neuroblastoma SH-SY5Y cells. Aggregability of isoD7-Abeta6-42 and Abeta6-42 was
      higher than that of full-length peptides Abeta42 and isoD7-Abeta42, while the
      repertoire of mouse brain Abeta binding proteins dramatically decreased. Abeta6
      42 and isoD7-Abeta6-42 exhibited higher neurotoxicity towards SH-SY5Y cells than
      Abeta42 and isoD7-Abeta42, respectively. They effectively stimulated production
      of ROS and NO, and also TNFalpha secretion by cells. Thus, our results suggest
      that ACE-dependent processing of full-length Abetas could result in formation of
      more pathogenic peptides.

PMID- 30282364
TI  - Positive Feedback Loops in Alzheimer's Disease: The Alzheimer's Feedback
      Hypothesis.
AB  - The dominant model for Alzheimer's disease (AD) is the amyloid cascade
      hypothesis, in which the accumulation of excess amyloid-beta (Abeta) leads to
      inflammation, excess glutamate and intracellular calcium, oxidative stress, tau
      hyperphosphorylation and tangle formation, neuronal loss, and ultimately
      dementia. In a cascade, AD proceeds in a unidirectional fashion, with events only
      affecting downstream processes. Compelling evidence now exists for the presence
      of positive feedback loops in AD, however, involving oxidative stress,
      inflammation, glutamate, calcium, and tau. The pathological state of AD is thus a
      system of positive feedback loops, leading to amplification of the initial
      perturbation, rather than a linear cascade. Drugs may therefore be effective by
      targeting numerous points within the loops, rather than concentrating on upstream
      processes. Anti-inflammatories and anti-oxidants may be especially valuable,
      since these processes are involved in many loops and hence would affect numerous
      processes in AD.

PMID- 30282365
TI  - The Novel DA-CH3 Dual Incretin Restores Endoplasmic Reticulum Stress and
      Autophagy Impairments to Attenuate Alzheimer-Like Pathology and Cognitive
      Decrements in the APPSWE/PS1DeltaE9 Mouse Model.
AB  - Alzheimer's disease (AD) afflicts more than 46.8 million people worldwide, with a
      newly diagnosed case every 3 seconds and no remission in the disease progression.
      The discovery of disease-modifying drugs is now on the summit of the
      neuropharmacological research priorities. The long-lasting derivatives of the
      insulinotropic incretin hormones-glucagon-like peptide 1 (GLP-1) and glucose
      dependent insulinotropic polypeptide (GIP)-have repeatedly been shown to cross
      the blood-brain barrier and counteract an array of deleterious effects across a
      range of experimental models of neuronal degeneration. Clinical trials for the
      efficacy of GLP-1 agonists in Alzheimer's and Parkinson's diseases have revealed
      beneficial effects of these anti-diabetic agents in halting neuronal degeneration
      progression. Herein, we examine whether the chronic treatment with the novel dual
      GLP-1/GIP receptor agonist DA-CH3 can restore the cognitive decline and AD-like
      cerebral pathology of the APPSWE/PS1DeltaE9 mouse model at the age of 10 months
      old. We report that once-a-daily, eight-week intraperitoneal administration of 25
      nmol/kg of the novel DA-CH3 dual-incretin analog rescues the spatial acquisition
      and memory impairments of this murine model that corresponds to the attenuation
      of the excessive plaque deposition, gliosis and synaptic damage in the
      APPSWE/PS1DeltaE9 brain. The amelioration of the AD-related pathology reflects
      the resolution of the endoplasmic-reticulum stress and derailed autophagy that
      both lay downstream of the rectified Akt signaling. Collectively, our findings
      endorse the beneficial effects of the incretin-based therapeutic approaches for
      the neurotrophic support of the AD brain and for the first time associate the
      incretin-induced neuroprotection with the proteostasis machinery in vivo.

PMID- 30282367
TI  - Class-Specific Incidence of All-Cause Dementia and Alzheimer's Disease: A Latent
      Class Approach.
AB  - Identifying preclinical Alzheimer's disease (AD) is an important step toward
      developing approaches to early treatment and dementia prevention. We applied
      latent class analysis (LCA) to 10 baseline neuropsychological assessments for
      1,345 participants from Einstein Aging Study. Time-to-event models for all-cause
      dementia and AD were run examining events in 4-year intervals. Five classes were
      identified: Mixed-Domain Impairment (n = 107), Memory-Specific Impairment (n =
      457), Average (n = 539), Frontal Impairment (n = 118), and Superior Cognition (n
      = 124). Compared to the Average class, the Mixed-Domain Impairment and Memory
      Specific Impairment classes were at higher risk of incident all-cause dementia
      and AD in the first 4 years from baseline, while the Frontal Impairment class was
      associated with higher risk between 4 and 8 years of follow-up. LCA identified
      classes which differ in cross-sectional cognitive patterns and in risk of
      dementia over specific follow-up intervals.

PMID- 30282368
TI  - Reappraisal of Abeta40 and Abeta42 Peptides Measurements in Cerebrospinal Fluid
      of Patients with Alzheimer's Disease.
AB  - Cerebrospinal fluid (CSF) biomarkers are currently included in the diagnostic
      criteria for Alzheimer's disease (AD), in particular, decreased concentrations of
      amyloid-beta peptide 1-42 (Abeta42) in the CSF, coupled with increased levels of
      tau and phosphorylated tau proteins, are supportive of AD diagnosis. To date, the
      quantification of Abeta42 levels with antibody-dependent immunoassay shows a
      marked variability among different laboratories and is also affected by different
      pre-analytical factors, suggesting that part of Abeta42 peptides might be
      aggregated and thus undetected by antibodies. To bypass an antibody-dependent
      measurement, we determined the Abeta40 and Abeta42 levels by immunoblot. We
      analyzed CSF samples from 35 patients with clinical diagnosis of probable AD and
      from 15 age-matched normal controls; CSF Abeta levels were determined by two
      different ELISA kits and by immunoblot analysis. Abeta40 levels measured by ELISA
      were comparable to those obtained by immunoblot, whereas CSF concentrations of
      Abeta42 measured by ELISA were significantly lower compared to values obtained by
      immunoblot quantification. Biochemical analysis, following 1D- and 2D-PAGE
      analysis, showed that the qualitative composition of Abeta peptides in the CSF is
      similar in AD and controls but different from that of AD brain tissues. Moreover,
      sedimentation velocity in sucrose gradient of CSF and brain homogenate from AD
      demonstrated that Abeta42 in CSF is different from Abeta42 in brain in terms of
      solubility and aggregation state.

PMID- 30282366
TI  - Incidence and Prevalence of Antiepileptic Medication Use in Community-Dwelling
      Persons with and without Alzheimer's Disease.
AB  - BACKGROUND: Although antiepileptic drugs (AEDs) have a potential for adverse drug
      reactions in older populations, little is known about their use in relation to
      Alzheimer's disease (AD) diagnosis. OBJECTIVES: In this study, we investigated
      the incidence and prevalence of AED use in relation to AD diagnosis. METHODS: The
      MEDALZ-study includes all Finnish persons who received clinically verified AD
      diagnoses (n = 70,718) during 2005-2011 and a matched comparison cohort without
      AD (n = 70,718). AD diagnoses were identified from the Special Reimbursement
      Register. We used the Prescription Register to identify dispensed AEDs. Incident
      AED users were identified with a one-year washout period 9-10 years before AD
      diagnosis, and incidence rates per 100 person-years were calculated for each six
      month period from nine years before to five years after AD diagnosis. Prevalence
      was assessed as proportion using AEDs during each six-month time period for
      incident use. RESULTS: Persons with AD were more likely to use AEDs during the
      study period (4.3%) than persons without AD (3.2%). The incidence and prevalence
      of AED use was higher among persons with AD and increased around the time of AD
      diagnosis. Epilepsy diagnoses did not explain these differences. Persons with AD
      were more likely to use older AEDs. CONCLUSION: Our study highlights the need to
      balance effective symptom control with the possible risks of treatment.

PMID- 30282369
TI  - Genetic Risk of Alzheimer's Disease: Three Wishes Now That the Genie is Out of
      the Bottle.
AB  - The availability and increasing popularity of direct-to-consumer genetic testing
      for the presence of an APOE4 allelle led the Alzheimer's Foundation of America
      Medical, Scientific and Memory Screening Advisory Board to identify three
      critical areas for attention: 1) ensure consumer understanding of test results;
      2) address and limit potential negative consequences of acquiring this
      information; and 3) support linking results with positive health behaviors,
      including potential clinical trial participation. Improving access to appropriate
      sources of genetic counseling as part of the testing process is critical and
      requires action from clinicians and the genetic testing industry. Standardizing
      information and resources across the industry should start now, with the input of
      consumers and experts in genetic risk and health information disclosure. Direct
      to-consumer testing companies and clinicians should assist consumers by
      facilitating consultation with genetic counselors and facilitating pursuit of
      accurate information about testing.

PMID- 30282371
TI  - France Will No More Reimburse Available Symptomatic Drugs Against Alzheimer's
      Disease.
AB  - The French Minister of Health published a decree on May 29th of 2018 removing the
      drugs used to fight against symptoms due to Alzheimer's disease (donepezil,
      rivastigmine, galantamine, memantine) from the list of available reimbursed
      drugs. This follows the advice delivered by the High Authority for Health in 2016
      and 2018 stating an "insufficient medical benefit and dangerousness because of
      significant side effects". The main French scientific and medical societies and
      professional associations want to state here their deep disagreement regarding
      this unfair decision. The evidence-based medicine related to these drugs reaches
      a high level in literature, whereas the clinical relevance of these treatments
      must be considered with co-prescription of psychosocial interventions and related
      approaches. As no serious pharmacovigilance signal has been provided by health
      authorities, the ratio of benefits/risks favors these drugs.

PMID- 30282372
TI  - Tetrabenazine Treatment Patterns and Outcomes for Chorea Associated with
      Huntington Disease: A Retrospective Chart Review.
AB  - BACKGROUND: Huntington disease (HD) is a neurodegenerative disorder characterized
      by motor impairments (including chorea), along with behavioral, psychiatric, and
      cognitive symptoms. Tetrabenazine was the first US Food and Drug Administration
      (FDA)-approved treatment for chorea related to HD. OBJECTIVE: To examine
      pharmacologic treatment patterns among patients using tetrabenazine, including
      reasons for treatment initiation, non-initiation, dose adjustments, and
      discontinuation, and to quantify the burden of chorea based on healthcare
      resource utilization. METHODS: In this retrospective patient chart review,
      neurologists were recruited from the Medefield (http://www.medefield.com) opt-in
      panel, and selected <=5 medical charts based on the criteria provided and
      abstracted data on demographics, disease history, healthcare resource use, and
      treatment patterns. RESULTS: 138 neurologists participated and 512 HD patient
      charts were reviewed. Among these patients, 26.4% did not initiate tetrabenazine.
      Most HD patients (66.5%) received a tetrabenazine dose <=50 mg. The most common
      reasons for stopping upward titration were optimal chorea control (55.5%),
      intolerability of higher doses (31.2%), and reaching the maximum recommended
      dosage despite suboptimal chorea control (11.4%). Chorea severity and non
      persistence to tetrabenazine were associated with increased emergency room
      visits, hospitalizations, and days hospitalized. CONCLUSIONS: Although
      tetrabenazine was the sole FDA-approved treatment for HD chorea until April 2017,
      more than one-quarter of respondents never initiated therapy. Tetrabenazine
      dosing was lower than predicted, and many patients experienced adverse symptoms
      of intolerability at high doses. New safer and more tolerable treatment options,
      such as deutetrabenazine, may improve treatment outcomes and reduce healthcare
      resource use.

PMID- 30282370
TI  - Tau Protein Dysfunction after Brain Ischemia.
AB  - Brain ischemia comprises blood-brain barrier, glial, and neuronal cells. The
      blood-brain barrier controls permeability of different substances and the
      composition of the neuronal cells 'milieu', which is required for their
      physiological functioning. Recent evidence indicates that brain ischemia itself
      and ischemic blood-brain barrier dysfunction is associated with the accumulation
      of neurotoxic molecules within brain tissue, e.g., different parts of amyloid
      beta protein precursor and changed pathologically tau protein. All these changes
      due to ischemia can initiate and progress neurodegeneration of the Alzheimer's
      disease-type. This review presents brain ischemia and ischemic blood-brain
      barrier as a trigger for tau protein alterations. Thus, we hypothesize that the
      changes in pattern of phosphorylation of tau protein are critical to microtubule
      function especially in neurons, and contribute to the neurodegeneration following
      brain ischemia-reperfusion episodes with Alzheimer's disease phenotype.

PMID- 30282374
TI  - How to Interpret Abnormal Findings of Spirometry and Manometry in Myotonic
      Dystrophies?
AB  - BACKGROUND/AIM: Pulmonary function tests are used for screening respiratory
      insufficiency in patients with myotonic dystrophy (DM). We analysed the agreement
      between two different approaches in assessment of abnormal findings of forced
      vital capacity (FVC), forced expiratory volume in the first second (FEV1),
      maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP), in DM
      patients. METHODS: We used Cohen's kappa- and Bangdiwala's B- statistic to
      compare the agreement between different cut-off values recommended by experts
      (ENMC) and the cut-off values based on the reference range (RR). We further
      analysed their sensitivity (Sn) and specificity (Sp) in detecting symptoms
      associated with respiratory insufficiency. RESULTS: The observed agreement was:
      1) for FVC: kappa= -0.002, B = 0.406; 2) for FEV1: kappa= 0.944, B = 0.946; 3)
      for MIP: kappa= 0.625, B = 0.674; and 4) for MEP: kappa= 0.241, B = 0.373.
      Overall, RR cut-off values showed higher sensitivity, whereas the ENMC values
      showed higher specificity in detecting symptoms of respiratory involvement.
      CONCLUSIONS: The two approaches showed perfect agreement in assessment of FEV1,
      substantial agreement for MIP, and weak agreement for FVC and MEP. RR is an
      established method of assessment for spirometry and should be favoured because it
      takes variability within the population into account. Further development and
      validation of regression equations for RR calculations of predicted maximal
      respiratory pressures, with corresponding lower limits of normal, is required.The
      B statistic is more robust in assessing agreement between two diagnostic methods,
      resolving the issue of the kappa paradox.

PMID- 30282373
TI  - Disability and Contextual Factors in Patients with Amyotrophic Lateral Sclerosis 
      A Three-Year Observational Study.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative
      disease characterized by muscle weakness and wasting. Observational natural
      history studies can give information on body function/structure impairments,
      activity limitations and participation restrictions, i.e. disability. Information
      needed to plan and develop care and support. OBJECTIVE: To describe and explore
      disease severity and impairments, activity limitations, participation
      restrictions and contextual factors over time. In specific, to explore concurrent
      presence of cognitive impairment, fatigue, anxiety, depression and pain, and
      whether these impairments were related to disease severity. METHODS: In this
      three-year observational study, 60 patients with ALS were included at baseline.
      Follow-ups were performed every 6 months unless participants had deceased or
      declined participation. Data was collected from medical records, and by study
      specific and standardized questionnaires administrated during home visits.
      RESULTS: Regardless of disease severity; fatigue, anxiety, depression and pain
      were present in patients with ALS at each data collection. Approximately one
      third experienced two or more of these impairments concurrently, i.e. at the same
      time point. Cognitive impairment could not be assessed in many patients due to
      their physical impairments. Disease severity was not associated with fatigue,
      anxiety, depression or pain. CONCLUSIONS: Patients with ALS need, throughout the
      course of the disease, to be regularly screened for commonly present impairments,
      activity limitations and participation restrictions so that person-centered
      interventions can be applied at the right time.

PMID- 30282376
TI  - Selective prophylactic solvent-detergent plasma and cryoprecipitate transfusion
      to prevent intraventricular hemorrhage in extreme preterm infants: A case
      historical control.
AB  - BACKGROUND: Contradictory evidence exists whether a prophylactic coagulation
      factor transfusion in the first hours of life (HOL) prevents intraventricular
      hemorrhage (IVH) in extreme preterm infants (EPI, <28 weeks gestation). We aimed
      to determine whether selective prophylactic solvent-detergent plasma and
      cryoprecipitate transfusion within 12 hours of life (SP-SDP/Cryoprecipitate-T)
      could prevent IVH in EPI. METHOD: This is a retrospective analysis, case
      historical control, of prospectively collected data from a pre-existing
      electronic neonatal database at a Saudi tertiary neonatal intensive care unit. We
      compared the IVH rate in EPI born in the first 4 years (Jan 2010-Dec 2013) of the
      SP-SDP/Cryoprecipitate-T period with that of EPI born during the last 4 years
      (Jan 2006-Dec 2009) of the rescue SDP/Cryoprecipitate-T period. RESULTS: The IVH
      rate was lower in the SP compared to the rescue- SDP/Cryoprecipitate-T period
      (30.8% versus 51.2%, odds ratio 0.42, 95% confidence interval 0.21, 0.88, p =
      0.02). This difference remained significant after controlling for six other IVH
      risk factors. CONCLUSIONS: Early SP-SDP/Cryoprecipitate-T may reduce the IVH rate
      in EPI. A large multicenter clinical trial is required for confirm the short and
      long-term benefit and risk of this intervention. Until then, early SP
      SDP/Cryoprecipitate-T may be considered by an institution with a persistently
      high IVH rate.

PMID- 30282375
TI  - Home-Based Monitoring of Pulmonary Function in Patients with Duchenne Muscular
      Dystroph.
AB  - BACKGROUND: Loss of pulmonary function is a main cause of early morbidity and
      mortality in patients with Duchenne muscular dystrophy (DMD). Standard of care
      guidelines recommend regular assessment of pulmonary function by hospital-based
      spirometry to detect onset and monitor progression of pulmonary function decline.
      OBJECTIVE: To assess the feasibility of home-based monitoring of pulmonary
      function by a hand-held device (HHD) in adolescent and adult patients with DMD
      over a period of 12 months. METHODS: In the phase III randomized placebo
      controlled DELOS trial in 10-18 year old DMD patients, peak expiratory flow (PEF)
      measurements were collected weekly at home by the patient (assisted by
      parent/caregiver) using a peak flow meter HHD. Adherence to the use of the HHD
      was assessed and 12-month changes in PEF as percent of predicted (PEF% p) for the
      idebenone (N = 31) and the placebo treatment groups (N = 33) from HHD-derived
      data were compared to results from hospital-based spirometry. RESULTS: A total of
      2689 individual HHD assessments were analysed. Overall adherence to the use of
      the HHD over the course of the 12-month study duration was good (75.9%, SD 21.5%)
      and PEF% p data obtained at the same day by HHD and standard spirometry
      correlated well (Spearman's rho 0.80; p < 0.001). Several analysis methods of HHD
      derived data for PEF% p consistently demonstrate that idebenone treatment slowed
      the decline in PEF% p compared to placebo, which supports the statistically
      significant difference in favour of idebenone for PEF% p measured by standard
      spirometry. CONCLUSIONS: This study demonstrates that home-based monitoring of
      pulmonary function in adolescent patients with DMD using a HHD is feasible,
      provides reliable data compared to hospital-based spirometry and is therefore
      suitable for use in clinical practice and for clinical trials.

PMID- 30282379
TI  - Recovery from apraxic deficits and its neural correlate.
AB  - BACKGROUND AND OBJECTIVE: Apraxia is a deficit of motor cognition leading to
      difficulties in actual tool use, imitation of gestures, and pantomiming object
      use. To date, little data exist regarding the recovery from apraxic deficits
      after stroke, and no statistical lesion mapping study investigated the neural
      correlate of recovery from apraxia. Accordingly, we here examined recovery from
      apraxic deficits, differential associations of apraxia task (imitation vs.
      pantomime) and effector (bucco-facial vs. limb apraxia) with recovery, and the
      underlying neural correlates. METHODS: We assessed apraxia in 39 patients with
      left hemisphere (LH) stroke both at admission and approximately 11 days later.
      Furthermore, we collected clinical imaging data to identify brain regions
      associated with recovery from apraxic deficits using voxel-based lesion-symptom
      mapping (VLSM). RESULTS: Between the two assessments, a significant recovery from
      apraxic deficits was observed with a tendency of enhanced recovery of limb
      compared to bucco-facial apraxia. VLSM analyses revealed that within the lesion
      pattern initially associated with apraxia, lesions of the left insula were
      associated with remission of apraxic deficits, whereas lesions to the (inferior)
      parietal lobe (IPL; supramarginal and angular gyrus) and the superior
      longitudinal fasciculus (SLF) were associated with persistent apraxic deficits.
      CONCLUSIONS: Data suggest that lesions affecting the core regions (and white
      matter) of the fronto-parietal praxis network cause more persistent apraxic
      deficits than lesions affecting other regions (here: the left insula) that also
      contribute to motor cognition and apraxic deficits.

PMID- 30282380
TI  - Alterations in mitochondrial membrane potential in peripheral blood mononuclear
      cells in Parkinson's Disease: Potential for a novel biomarker.
AB  - BACKGROUND: Progressive apoptosis in the dopaminergic neurons of substantia nigra
      lead to Parkinson's disease. Since neurons require substantially higher supply of
      energy, their mitochondria have a pivotal status in neuronal survival. These
      organelles have a key role to play in apoptosis and any impairment thereof may
      lead to apoptosis mediated cell death. OBJECTIVES: To evaluate and compare the
      mitochondrial membrane potential (Deltapsi) in Parkinson's disease patients and
      healthy controls. METHODS: We evaluated the mitochondrial membrane potential
      (Deltapsi) in the peripheral blood mononuclear cells by Flow cytometry using a
      lipophillic cationic dye JC-1 in Parkinson's disease patients (N = 61) and
      healthy controls (N = 37). RESULTS: JC-1 fluorescence was measured and
      represented as percentage positivity i.e., Mean+/-SEM in FL-2 (representing non
      apoptotic aggregates) and FL-1 (indicating apoptotic cell population having
      depolarized or damaged mitochondria) channels. The ratio of % FL-2 and % FL-1,
      which is an indicator of cellular mitochondrial membrane potential, was found to
      be significantly higher in healthy controls (Mean+/-SEM = 60.48+/-18.42) as
      compared to patients (Mean+/-SEM = 24.30+/-4.671) in both stimulated and
      unstimulated conditions. CONCLUSIONS: Mitochondrial membrane potential is altered
      and hence its evaluation in peripheral blood mononuclear cells may serve as an
      early marker of apoptosis in PD and, therefore, may pave way for early
      interventions. Since Deltapsi has a role in the maintenance of electrochemical
      gradient, the disruption of which may lead to neuronal apoptosis, Deltapsi is
      intricately nested within etiopathogenesis of PD and may prove to be useful in
      design of diagnostics, prognostics and therapeutics for PD.

PMID- 30282381
TI  - Egg yolk immunoglobulins' impact on experimental periodontitis caused by
      Porphyromonas gingivalis.
AB  - BACKGROUND: Periodontitis is a chronic inflammatory disease caused by
      Porphyromonas gingivalis that leads to a series of periodontal tissue injuries.
      Egg yolk immunoglobulins (IgY) is procuded in egg yolk and inhibits P.
      gingivalis. OBJECTIVE: The aim was to evaluate the effect of IgY on experimental
      periodontitis caused by P. gingivalis. METHODS: The second molars of rats were
      ligatured using medical 5-0 silk and smeared with P. gingivalis to induce
      experimental periodontitis. Then, the rats were smeared with 2 mL IgY solutions
      or 0.9% NaCl in the oral cavity for up to 4 wk. The scores for gingival index,
      plaque index and probe on bleeding, the levels of IL-6 and TNF-alpha, X-ray
      radiography and histology were used to determine the efficacy of the IgY on
      experimental periodontitis. RESULTS: The clinical indices improved; the levels of
      IL-6 and TNF-alpha were significantly (p< 0.05) decreased; the X-rays and
      histomorphological observations suggested that the periodontal inflammation and
      periodontitis were alleviated compared to the control. CONCLUSIONS: IgY showed
      significant effects on anti-inflammatory, anti-coaggregation activity, and
      protected against alveolar bone loss. Therefore, it had a beneficial effect on
      preventing experimental periodontitis caused by P. gingivalis.

PMID- 30282382
TI  - The effects of a posterior superior iliac spine support device on upper trunk
      acceleration during gait in individuals with flat lumbar back posture.
AB  - BACKGROUND: The orientation of the pelvis is of particular importance to the
      sagittal curve of the spine and has geometric relationships with the top of the
      spine and lumbar lordosis. Changes in spinal shape or disruptions of sagittal
      balance in the spine, such as a flattened lumbar spine, have significant negative
      effects. OBJECTIVE: The aim of this study was to investigate the effects of the
      posterior superior iliac spine support device (PSD) on upper trunk acceleration
      during gait in individuals with flat lumbar back posture. METHODS: In total, 10
      young male subjects with reduced lumbar lordosis (global lumbar lordosis angle
      (T10-S2): <-20?) were recruited for this study. Participants walked 7 m with and
      without wearing a PSD at a self-selected speed while fitted with an accelerometer
      attached over the T7 spinous process. RESULTS: The normalized AP acceleration of
      T7 with PSD (40.57 +/- 11.22%) was significantly higher than those without PSD
      (37.10 +/- 10.46%, p= 0.035). CONCLUSIONS: We found that wearing the PSD
      immediately improved pelvic physiological movement during walking in individuals
      with lumbar flat back posture. Our findings may help healthcare professionals
      manage flat back posture in asymptomatic younger individuals.

PMID- 30282383
TI  - The occlusion effect in bone conducted cVEMP.
AB  - BACKGROUND: Vestibular evoked myogenic potentials (VEMP) are transient alteration
      in tonic activity of muscles elicited by auditory stimulation of the otolithic
      organs of the ear. VEMP can be triggered by auditory stimulation via air or bone
      conduction. Occlusion of the external auditory meatus has long been known to
      decrease thresholds for sound perception medicated by the cochlea. OBJECTIVE:
      Proof that the occlusion effect is present for bone conducted (BC) cervical VEMPs
      (cVEMP). METHODS: Measurement of the thresholds and raw amplitudes of BC-VEMPs in
      twenty healthy adults with the external auditory canal open and occluded.
      RESULTS: Thresholds for BC-VEMPs were similar for the open vs. the occluded
      condition. However, amplitudes were statistically significantly higher in the
      occluded (average 76.34MUV) vs. open group (average 69.9MUV). CONCLUSIONS: The
      occlusion effect is present in cVEMPs. This finding, described herein for the
      first time, has a number of clinical implications such as the surgically altered
      ear and the use of occluding hearing aids.

PMID- 30282384
TI  - Vestibular dysfunction, beyond benign paroxysmal positional vertigo, affects
      mental rotations: Comment on "Visual dependence and spatial orientation in benign
      paroxysmal positional vertigo".

PMID- 30282385
TI  - Letter to the Editor.

PMID- 30282386
TI  - From the Editor.

PMID- 30282387
TI  - Reframing Medicare Physician Payment Policy for 2019: A Look at Proposed Policy.
AB  - : On July 12, 2018, the Centers for Medicare and Medicaid Services (CMS) released
      the proposed 2019 Medicare physician fee schedule and quality payment program,
      combining these 2 rules for the first time. This occurred in a milieu of changing
      regulations that have been challenging for interventional pain management
      specialists. The Affordable Care Act (ACA) continuous to be amended by multiple
      administrative changes. This July 12th rule proposes substantial payment changes
      for evaluation and management (E&M) services, with documentation requirements,
      and blending of Level II to V CPT codes for E&M into a single payment. In
      addition, various changes in the quality payment program with liberalization of
      some metrics have been published. Recognizing that there are differing impacts
      based on specialty and practice type, as a whole interventional pain management
      specialists would likely see favorable reimbursement trends for E&M services as a
      result of this proposal. Moreover, in comparison with recent CMS final ruling,
      this proposed rule has relatively limited changes in procedural reimbursement
      performed in a facility or in-office setting.CMS, in the new rule, has proposed
      an overhaul of the E&M documentation and coding system ostensibly to reduce the
      amount of time physicians are required to spend inputting information into
      patients' records. The new proposed rule blends Level II to V codes for E&M
      services into a single payment of $93 for office outpatient visits for
      established patients and $135 for new patient visits. This will also have an
      effect with blended payments for services provided in hospital outpatients. CMS
      also has provided additional codes to increase the reimbursement when prolonged
      services are provided with total reimbursement coming to Level V payments.
      Interventional pain management-centered care has been identified as a specialty
      with complexity inherent to E&M associated with these services. Among the
      procedural payments, there exist significant discrepancies for the services
      performed in hospitals, ambulatory surgery centers (ASCs), and offices. A
      particularly egregious example is peripheral neurolytic blocks, which is
      reimbursed at 1,800% higher in hospital outpatient department (HOPD) settings as
      compared with procedures done in the office. The majority of hospital based
      procedures have faced relatively small cuts as compared with office based
      practice. The only significant change noted is for spinal cord stimulator implant
      leads when performed in office setting with 19.2% increase. However, epidural
      codes, which have been initiated with a lower payment, continue to face small
      reductions for physician portion.This review describes the effects of the
      proposed policy on interventional pain management reimbursement for E&M services,
      procedural services by physicians and procedures performed in office settings.
      KEY WORDS: Physician payment policy, physician fee schedule, Medicare, Merit
      Based Incentive Payment System, interventional pain management, regulatory
      tsunami, Medicare Access and CHIP Reauthorization Act of 2015.

PMID- 30282388
TI  - Efficacy Assessment of Radiofrequency Ablation as a Palliative Pain Treatment in
      Patients with Painful Metastatic Spinal Lesions: A Systematic Review.
AB  - BACKGROUND: Metastatic spinal lesions are difficult-to-treat entities that are
      most commonly associated with pain and severely reduced health-related quality of
      life (HRQoL). Within the last 5 to 10 years, radiofrequency ablation (RFA) has
      emerged as an option in the palliative treatment of vertebral metastases.
      OBJECTIVES: Our review aims to evaluate the clinical effectiveness and safety of
      RFA, mostly in combination with vertebroplasty, in patients with painful
      vertebral metastases. STUDY DESIGN: The design of this study is a systematic
      review. METHODS: We conducted a systematic literature search and a manual search
      of 5 databases in December 2016. The review applied a methodological framework
      based on the HTA Core Model(r). Data on each selected outcome category were
      synthesized according to the Grading of Recommendations, Assessment, Development
      and Evaluation (GRADE) scheme. Risk of bias was assessed using the Institute of
      Health Economics (IHE) Risk of Bias checklist for case series. RESULTS: We
      identified 299 citations. After applying the inclusion criteria, a total of 9
      studies (4 prospective and 5 retrospective studies) were determined to be
      eligible. These studies included a total of 583 patients with vertebral
      metastases who were treated with RFA and, in most cases, received an additional
      vertebroplasty treatment (n = 437). The studies were categorized as having a
      moderate to high risk of bias. The strength of evidence was found to be "very
      low" for safety outcomes and could not be assessed for efficacy outcomes. Current
      evidence suggests that RFA leads to significant pain reduction. Furthermore, no
      major complications occurred when using RFA. LIMITATIONS: A major concern is the
      low number of included patients and heterogeneity of study characteristics in
      most of the studies. The low number of patients also impeded comparison of the
      effectiveness of RFA alone to RFA in combination with vertebroplasty. CONCLUSION:
      According to the available evidence, RFA may be safe and effective, especially
      for patients with painful vertebral metastases who show contraindications or
      unresponsiveness to conventional therapies (e.g., radiation) or for those who are
      at risk of tumor progression. KEY WORDS: Radiofrequency ablation, vertebral
      metastases, metastatic spinal lesions, pain, clinical effectiveness, safety,
      palliative pain treatment.

PMID- 30282389
TI  - Comparison of Clinical Efficacy Between Transforaminal and Interlaminar Epidural
      Injections in Lumbosacral Disc Herniation: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Epidural injection (EI) is used to treat back or radicular pain from
      lumbosacral disc herniation (LDH). Although several reports have stated that the
      transforaminal approach in EI (TFEI) has an advantage in target specificity and
      yields better clinical efficacy than the interlaminar approach in EI (ILEI),
      other studies have indicated that the clinical efficacy of ILEI was not inferior
      to that of TFEI and that ILEI also has the ability to spread medication into the
      ventral space to a degree similar to that of TFEI. There has been controversy
      about whether TFEI is superior to ILEI in clinical efficacy. OBJECTIVES: This
      systematic review and meta-analysis aimed to investigate whether TFEI is more
      useful than ILEI for achieving clinical outcomes in patients with LDH. STUDY
      DESIGN: A systematic review and meta-analysis using a random effects model on
      randomized controlled studies (RCT). METHODS: A literature search was performed
      in MEDLINE, EMBASE, Cochrane review, and KoreaMed for studies published from
      January 1996 until July 2017. From those found fulfilling the search criteria,
      manuscripts that compared the clinical efficacy of steroids and control agents,
      such as local anesthetics or saline, in terms of pain control and functional
      improvement were included in this study. Exclusion criteria included a previous
      history of lumbosacral surgery, non-specific low back pain, severe spinal
      stenosis, and severe disc degeneration. After reviewing titles, abstracts, and
      the full text of 6,711 studies; 12 studies were included in the qualitative
      synthesis. Data including pain scores, functional scores, and follow-up period
      were extracted from 10 studies and analyzed using a random effects model to
      obtain effect size and its statistical significance. The quality and level of
      evidence were analyzed in accordance with the Grading of Recommendations
      Assessment, Development and Evaluation (GRADE) methodology. RESULTS: In terms of
      pain control, TFEI showed significantly better short-term (2 weeks to 1 month)
      outcomes and slightly favorable long-term (4 - 6 month) outcomes, but without
      significance, in comparison with ILEI. In terms of functional improvement, TFEI
      also showed favorable short- and long-term outcomes, but without significance, in
      comparison with ILEI. TFEI had target specificity, required no additional cost
      and resources, and had equal applicability to ILEI. However, TFEI was more
      associated with a higher frequency of discomfort or adverse events during the
      procedure. Overall, better results were reported with TFEI over ILEI, but with
      low-grade evidence due to the inconsistency and imprecision of the selected
      studies. LIMITATION: Analyses of safety or adverse effects could not be performed
      due to a lack of available data from the included studies. CONCLUSIONS: Based on
      low-grade evidence, TFEI showed significantly better short-term pain control and
      slightly favorable outcomes in long-term pain reduction and short- and long-term
      functional improvement in comparison with ILEI. KEY WORDS: Epidural injection,
      interlaminar, transforaminal, meta-analysis, systemic review, pain, function.

PMID- 30282390
TI  - Comparison of Clinical Efficacy of Epidural Injection With or Without Steroid in
      Lumbosacral Disc Herniation: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Epidural injection is performed for treatment of back and radicular
      pain in patients with lumbosacral disc herniation (LDH). Steroids are usually
      administered to effectively remove inflammatory mediators, and local anesthetics
      or saline also contribute to pain reduction by washing out chemical mediators or
      blocking the nociceptor activity. Controversy exists regarding whether steroids
      produce superior clinical effects compared with local anesthetics or saline.
      OBJECTIVES: This study investigated whether epidural injection of steroids
      produces better clinical effects than local anesthetics or saline in the
      treatment of LDH. STUDY DESIGN: A literature search was performed in MEDLINE,
      EMBASE, Cochrane review, and KoreaMed for studies published from January 1996
      until July 2017. From among the studies fulfilling the search criteria, those
      that compared the clinical efficacy of steroids and control agents, such as local
      anesthetics or saline, in terms of pain control and functional improvement were
      included in this study. Exclusion criteria included a previous history of
      lumbosacral surgery, non-specific low back pain, severe spinal stenosis, and
      severe disc degeneration. SETTING: A systematic review and meta-analysis using a
      random effects model on randomized controlled studies (RCTs). METHODS: After
      reviewing titles, abstracts, and full texts of 6,711 studies that were chosen
      following removal of duplicates after the initial database search, 15 randomized
      controlled studies were included in our qualitative synthesis. Data including
      pain score, functional score, and follow-up period were extracted from 14 studies
      and analyzed using a random effects model to calculate the effect size and its
      corresponding statistical significance. Quality and level of evidence were
      established in accordance with the Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) methodology. RESULTS: Steroids and local
      anesthetics were shown to be effective. Steroid showed significantly better pain
      control than control agents at 1 month, 3 months, and 6 months. The superiority
      of steroid in pain control was more prominent at one month, but diminished from 3
      months to 1 year, showing no significant superiority in terms of mean difference,
      With respect to functional score, no significant difference was observed between
      steroids and control agents. The subgroup analysis showed that steroid revealed
      significant superiority in pain and functional score at 1 month to saline rather
      than local anesthetics. Generally, the quality of included studies was evaluated
      as high-grade, but the evidence level was determined to be moderate, due to
      inconsistencies. LIMITATION: Analyses of safety or adverse effects could not be
      performed due to a lack of available data from the included studies. CONCLUSIONS:
      Steroid is recommended over local anesthetics or saline for pain control in
      patients with LDH, with a weak strength of recommendation. The superiority of
      steroids was remarkable, especially at relatively short-term follow-ups, and
      maintained until the 1 year follow-up. The clinical benefits of steroids at 1
      month were more prominent when compared with saline, than when compared with
      local anesthetics. KEY WORDS: Steroid, local anesthetics, saline, epidural
      injection, pain, function, meta-analysis, systemic review.

PMID- 30282391
TI  - Effectiveness and Safety of High-Voltage Pulsed Radiofrequency to Treat Patients
      with Primary Trigeminal Neuralgia: A Multicenter, Randomized, Double-Blind,
      Controlled Study Protocol.
AB  - BACKGROUND: Trigeminal neuralgia (TN) is a neurological syndrome characterized by
      paroxysmal, lightning-like, severe pain in the facial area innervated by the
      trigeminal nerve. Patients who do not respond well to drug treatment can undergo
      a nerve block, a traditional conservative treatment. Pulsed radiofrequency (PRF)
      is a nondestructive pain intervention technique. However, its treatment
      effectiveness for TN has rarely been reported and remains controversial among
      scholars. A recent single-center preliminary clinical study showed that high
      voltage PRF was significantly effective in the treatment of TN. However, whether
      high-voltage PRF is a viable pain treatment option for TN patients who are
      unresponsive to drug treatment must still be confirmed with standardized clinical
      studies by utilizing conservative nerve block treatment as a control. OBJECTIVE:
      To compare the effectiveness and safety of high-voltage PRF and nerve block for
      primary TN patients who have failed to respond to pharmacological treatment and
      who are seeking a better non-surgical treatment option. STUDY DESIGN:
      Prospective, multicenter, randomized, double-blind, controlled clinical trial.
      SETTING: Three interventional pain management centers in Beijing, China. METHODS:
      The study will include 134 consecutive patients with primary TN who have failed
      to respond to drug treatment. The patients will be randomly assigned to 2 groups,
      the nerve block group and the PRF group. The nerve block group will be slowly
      injected with 1.4 mL of a mixture of dexamethasone and lidocaine after 360 s of
      sham PRF treatment, and 0.5 mL of normal saline will be administered before the
      needle is withdrawn. The PRF group will undergo 360 s of 42 degrees C PRF
      treatment at the highest output voltage that the patients can tolerate, after
      which the patients will be injected with the same concentration and volume of
      lidocaine and normal saline that the nerve block group receives. The Barrow
      Neurological Institute (BNI) pain intensity scale will be used to assess the
      degree of pain relief before and after the treatment. RESULTS: The effectiveness
      and safety of high-voltage PRF and nerve block to treat TN will be analyzed to
      determine significant differences in pain relief and functional improvement. The
      primary efficacy outcome measure is the response rate at one-year post-operation
      (BNI I-III/total number of cases*100%). Secondary efficacy outcome measures
      include the response rate at postoperative day 1, week 1, week 2, month 1, month
      3, month 6 and year 2, the patient satisfaction score (PSS) at various time
      points, the dosage of antiepileptic drugs (milligrams per day), and information
      regarding patients with a BNI score of IV or V who switch to other therapies.
      LIMITATIONS: The effects of the waveform, treatment duration, frequency and other
      parameters of PRF deserve further investigation. CONCLUSIONS: This is the first
      multicenter, double-blind, randomized controlled study to compare the efficacy
      and safety of PRF and nerve block to treat TN patients who have failed to respond
      to drug treatment. Moreover, the value of PRF in TN treatment may need to be
      clinically clarified with evidence-based medical support and other advanced
      studies. KEY WORDS: Trigeminal neuralgia, effectiveness, safety, pulsed
      radiofrequency.

PMID- 30282392
TI  - Preemptive Analgesia with Parecoxib in Total Hip Arthroplasty: A Randomized,
      Double-Blind, Placebo-Controlled Trial.
AB  - BACKGROUND: Total hip arthroplasty (THA) is a well-accepted surgical treatment
      for terminal hip diseases. OBJECTIVE: To evaluate the effect of preemptive
      analgesia with parecoxib in patients undergoing primary unilateral THA. STUDY
      DESIGN: A randomized, double-blind, placebo-controlled study. SETTING: This study
      was conducted at Peking Union Medical College Hospital and Beijing Jishuitan
      Hospital in Beijing, China. METHODS: A total of 94 patients scheduled for primary
      unilateral THA in 2 centers (Peking Union Medical College Hospital and Beijing
      Jishuitan Hospital) were randomly assigned to receive 40 mg parecoxib (n = 48) or
      0.9% normal saline solution (n = 46) 30 minutes before incision. All patients
      received standardized intravenous patient-controlled analgesia (PCA)
      postoperatively. Preoperative baseline data, surgery-related conditions,
      postoperative Visual Analog Scale (VAS) pain score, cumulative narcotic
      consumption of PCA, and complications were compared between the parecoxib group
      and the placebo group. RESULTS: There were no significant differences in
      postoperative VAS pain score, cumulative narcotic consumption of PCA, proportion
      of analgesic remedy, and complications between the 2 groups. LIMITATIONS: Only a
      single dose of parecoxib was used without including a dose-dependent control
      group. CONCLUSION: A single dose of parecoxib 30 minutes before incision did not
      provide effective preemptive analgesia for the management of postoperative pain
      after primary unilateral THA. The possible effect of preemptive analgesia with
      parecoxib needs further investigation. KEY WORDS: Total hip arthroplasty, pain,
      parecoxib, COX-2 selective inhibitor, preemptive analgesia, clinical trial,
      patient-controlled analgesia, analgesics.

PMID- 30282393
TI  - Comparison of Efficacy of Lateral Branch Pulsed Radiofrequency Denervation and
      Intraarticular Depot Methylprednisolone Injection for Sacroiliac Joint Pain.
AB  - BACKGROUND: Sacroiliac joint dysfunctional pain has always been an enigma to the
      pain physician, whether it be the diagnosis or the treatment. Diagnostic blocks
      are the gold standard way to diagnose this condition. Radiofrequency neurotomy of
      the nerves supplying the sacroiliac joint has shown equivocal results due to
      anatomical variation. Intraarticular depo-steroid injection is a traditional
      approach to treating sacroiliac joint pain. For long-term pain relief, however,
      lesioning the sacral lateral branches may be a better approach. OBJECTIVE: This
      study compared the efficacy of intraarticular depo-methylprednisolone injection
      to that of pulsed radiofrequency ablation for sacroiliac joint pain. STUDY
      DESIGN: This study used a randomized, prospective design. SETTING: Thirty
      patients with diagnostic block-confirmed sacroiliac joint dysfunctional pain were
      randomly assigned to 2 groups. One group received intraarticular
      methylprednisolone and another group underwent pulsed radiofrequency of the L4
      medial branch, the L5 dorsal rami, and the lateral sacral branches. RESULTS:
      Reduction in Numeric Rating Scale (NRS) for pain at 1 month post-procedure
      remained similar in Group A, while in Group B few patients reported a further
      decrease in the NRS score (3.333 +/- 0.4880 and 2.933 +/- 0.5936, respectively).
      At 3 months post-procedure, the NRS score began to rise in most patients in group
      A, while in Group B, the NRS score remained the same since the last visit (4.400
      +/- 0.9856 and 3.067 +/- 0.8837, respectively). At 6 months post-procedure, the
      NRS score began to rise further in most patients in group A. In Group B, the NRS
      score remained the same in most of the patients since the last visit (5.400 +/-
      1.549 and 3.200 +/- 1.207). There was a marked difference between the 2 groups in
      Oswestry Disability Index (ODI) scores at 3 months post-procedure (Group A,
      12.133 +/- 4.486 vs Group B, 9.133 +/- 3.523) and at 6 months post-procedure
      there was a significant (P = 0.0017) difference in ODI scores between Group A and
      Group B (13.067 +/- 4.284 and 8.000 +/- 3.703, respectively). Global Perceived
      Effect (GPE) was assessed in both groups at 3 months post-procedure Only 33.3%
      (Confidence Interval (CI) of 11.8- 61.6 ) of patients in Group A had positive GPE
      responses whereas in Group B, 86.67% (CI of 59.5- 98.3 ) of patients had positive
      GPE responses. At 6 months post-procedure, the proportion of patients with
      positive GPE declined further in Group A, while in Group B, positive GPE
      responses remained the same (20% with a CI of 4.30- 48.10 and 86.67% with a CI of
      59.5- 98.3, respectively ). LIMITATIONS: Small sample size. CONCLUSION: This
      comparative study shows that pulsed radiofrequency denervation of the L4 and L5
      primary dorsal rami and S1-3 lateral branches provide significant pain relief and
      functional improvement in patients with sacroiliac joint pain. KEY WORDS: Low
      back pain, sacroiliac joint dysfunctional pain, radiofrequency, intraarticular
      injection.

PMID- 30282394
TI  - Low Volume Neurolytic Retrocrural Celiac Plexus Block for Visceral Cancer Pain:
      Retrospective Review of 507 Patients with Severe Malignancy Related Pain Due to
      Primary Abdominal Cancer or Metastatic Disease.
AB  - BACKGROUND: Abdominal pain from primary cancer or metastatic disease is a
      significant cause of pain for patients undergoing treatment for the disease.
      Patient's pain may be resistant to conventional analgesics. The need for timely
      pain relief in order to facilitate further care in the cancer treatment plan
      should be a priority. OBJECTIVES: The aim of this retrospective observational
      review was to assess the relief given with a low volume neurolytic retrocrural
      celiac plexus nerve block, the duration of the procedure, the duration of relief,
      the reduction in daily opioid consumption, and the improvement of quality of life
      in a patient suffering from incapacitating abdominal pain due to primary
      abdominal malignancy or abdominal metastatic disease. Patients were given a
      neurolytic celiac plexus block without previous diagnostic block due to multiple
      comorbidities. STUDY DESIGN: This is a retrospective, observational study.
      METHODS: Five hundred and seven patients were studied and data at 5 months for
      455 patients were retained at the end of the review. They were evaluated in the
      pain center prior to and after the neurolytic retrocrural celiac plexus nerve
      block under fluoroscopic guidance. They were assessed on duration of procedure,
      pain scores (numeric rating scale 0-10), daily opioid consumption, quality of
      life improvement (simple yes or no question at 3 months) and routine follow-up
      during treatment for the cancer for 6 months or end of life. All data was
      gathered by extensive chart review and placed on a spreadsheet for analysis.
      RESULTS: Follow-up was completed 6 months after the procedure. Pain scores, daily
      opioid consumption, and quality of life showed improvement for the duration of
      the study. There was some return in pain during the fourth to sixth month due to
      disease progression and the anticipated duration of the neurolytic agent. Some
      short duration known side effects did occur. An initial vascular contrast uptake
      of 6.7% was noted during the procedure while utilizing digital subtraction
      angiography with fluoroscopy. LIMITATIONS: A larger sample size would be ideal,
      as well as, a prospective trial with a control group, but this is unrealistic in
      our patient population. A proven quality of life questionnaire would be
      beneficial. Comparing alcohol, phenol and radiofrequency thermocoagulation would
      be interesting to equate duration, effect, and side effects. CONCLUSION: Low
      volume neurolytic retrocrural celiac plexus nerve block with phenol is a safe
      procedure providing up to 6 months of pain relief and is an effective, well
      established, minimally time-consuming procedure for abdominal pain due to primary
      malignancy or metastatic spread. KEY WORDS: Celiac plexus, neurolytic, abdominal
      cancer pain, pain, retrocrural, cancer pain.

PMID- 30282395
TI  - A Retrospective Review of Spinal Radiofrequency Neurotomy Procedures in Patients
      with Metallic Posterior Spinal Instrumentation - Is it Safe?
AB  - BACKGROUND: Recent studies have shown that medial branch radiofrequency neurotomy
      (RFN) procedures done at the level of a pedicle screw can increase pedicle screw
      temperature, and it has been speculated that pedicle screw heating may cause
      thermal injury. There has been a limited amount of investigation into the real
      world safety profile of RFN procedures in patients with pedicle screws.
      OBJECTIVES: We aim to demonstrate that the occurrence of serious adverse events
      is rare for a medial branch RFN procedure completed at a level with metallic
      spinal hardware when performed according to the Spine Intervention Society
      practice standards. STUDY DESIGN: This study involved retrospective chart reviews
      of every patient who received an RFN procedure for spinal facet joint pain during
      the 5-year time period from 2012-2016. SETTING: The research took place within a
      single university-based interventional pain management center. METHODS: The study
      sample included 507 patient charts. Data collection included patient
      demographics, RF denervation sites at a level with metallic hardware, and all
      serious RF-related complications that could be attributable to heated metallic
      hardware. The research team developed medical-chart abstraction criteria for each
      of the following categorized complications: a) superficial burns, b) deep burns,
      c) denervation of dorsal ramus, d) denervation of ventral ramus, and e)
      coagulation of a spinal vascular structure. RESULTS: Of the 36 patients who met
      the inclusion criteria for this study, 43.6% were men and 56.4% were women. The
      mean age was 59.5 years old, with an age range of 25 to 87 years. There were a
      total of 56 ablations performed at a level with metallic spinal hardware, of
      which 11 were cervical, 44 were lumbar, and 1 was thoracic . There were zero
      documented complications found among our patient population in any of the 5
      categories of serious complications. LIMITATIONS: As a retrospective chart
      review, this study was dependent on the availability and accuracy of medical
      records. Chart abstraction criteria for each outcome measure were developed by
      the research team without scientific testing. CONCLUSIONS: There have been no
      reported complications attributable to hardware temperature increases when
      performing medial branch RFNs at the level of a pedicle screw. For safety, it is
      important to use multiplanar fluoroscopic imaging techniques to ensure that the
      RFN cannula is not in contact with the pedicle screw. KEY WORDS: Radiofrequency
      neurotomy, medial branch nerve ablation, safety, thermal injuries, metallic
      spinal hardware, pedicle screws, lateral mass screws, cervical facet joints,
      severe complications, adverse events.

PMID- 30282396
TI  - Earlier Vertebroplasty for Osteoporotic Thoracolumbar Compression Fracture May
      Minimize the Subsequent Development of Adjacent Fractures: A Retrospective Study.
AB  - BACKGROUND: Percutaneous vertebroplasty (PVP) is widely used to treat
      osteoporotic vertebral compression fractures (OVCFs). The influence of timing
      (early vs. late) of PVP on the development of adjacent vertebral fractures (AVF)
      has rarely been discussed. OBJECTIVE: This study aimed to compare the incidence
      of AVF among patients who received early PVP (= 30 days after symptom onset,
      EPVP) or late PVP (> 30 days after symptom onset, LPVP) in the thoracolumbar
      region (T10 to L2) after a 1-year follow up. STUDY DESIGN: A retrospective cohort
      study. SETTING: Department of Orthopedic, an affiliated hospital of a medical
      university. METHODS: Patients who had single-level, T-score = -2.5 of lumbar bone
      mineral density (BMD), primary OVCF in the thoracolumbar region (T10 to L2) and
      who received PVP between July 2012 and June 2014 were included in the study. They
      were divided into early PVP and late PVP groups according to the interval between
      symptom onset and treatment. The risk factors associated with subsequent AVFs
      were analyzed. RESULTS: Of the 225 patients reviewed, 124 met the criteria and
      were followed for a minimum of 1 year. Eleven patients (14.1%) in the EPVP group
      (n = 78) and 18 patients (39.1%) in the LPVP group (n = 46) experienced an AVF
      during the first year following vertebroplasty. Outcomes were significantly
      better in patients with higher bone mineral density, lower cement volume, and
      without cement leakage (P < 0.01). Cox regression indicated an increase risk for
      AVF for LPVP, with an adjusted hazard ratio of 6.08 (95% confidence interval:
      2.50-14.81). LIMITATION: The incidence of AVFs could be over estimated due to
      this being a retrospective study with a small case number and lack of either
      biomechanical study of intra-vertebral cement distribution by times to support
      the result. CONCLUSIONS: Compared with later interventions, PVP performed within
      30 days after fracture development may be associated with a lower risk of
      adjacent fractures in the thoracolumbar region. KEY WORDS: Percutaneous
      vertebroplasty, osteoporosis, osteoporotic vertebral compression fracture,
      adjacent vertebral fracture.

PMID- 30282397
TI  - Variations in Interlaminar Epidural Steroid Injection Practice Patterns by
      Interventional Pain Management Physicians in the United States.
AB  - BACKGROUND: Previous surveys have identified variations in practice patterns
      related to epidural steroid injections. Since then, the United States Food and
      Drug Administration (FDA) has required the addition of drug warning labels for
      injectable corticosteroids. Updated evidence, as well as scrutiny from regulatory
      agencies, may affect practice patterns. OBJECTIVE: To provide an update on
      interlaminar epidural steroid injection (ILESI) practice patterns, we surveyed
      interventional pain management (IPM) physicians in the United States. STUDY
      DESIGN AND SETTING: This was a cross-sectional survey of IPM physicians in the
      United States. METHODS: A web-based survey was distributed to IPM physicians in
      the United States selected from the Accreditation Council for Graduate Medical
      Education accredited pain medicine fellowship program list as well as the
      American Society of Interventional Pain Physicians membership database.
      Physicians were queried about ILESI practices, including needle size, use of
      image guidance, level of injection, identification of the epidural space, and
      preference for injectate. RESULTS: A total of 249 responses were analyzed. All
      respondents used image guidance for ILESI. There were variations in needle size,
      use of contrast, number of fluoroscopic views utilized, technique for identifying
      the epidural space, and choice of injectate. LIMITATIONS: The response rate is a
      limitation, thus the results may not be representative of all United States IPM
      physicians. CONCLUSIONS: Though all respondents used image guidance for ILESI,
      variations in other ILESI practices still exist. Since the closure of this
      survey, a multi-society pain workgroup published recommendations regarding ESI
      practices. Our survey findings support the need for more evidence-based
      guidelines regarding ESI. KEY WORDS: Epidural injection, epidural steroids,
      survey, low back pain, neck pain, technique.

PMID- 30282398
TI  - Comparison of 3 Approaches to Percutaneous Epidural Adhesiolysis and Neuroplasty
      in Post Lumbar Surgery Syndrome.
AB  - BACKGROUND: Percutaneous epidural adhesiolysis and neuroplasty (PEAN) has been
      proven to be safe and effective in treating different spine pathologies, in
      particular post lumbar surgery syndrome (PLSS). OBJECTIVES: The purpose of this
      study was to compare the efficacy and complication rates of the 3 different PEAN
      anatomical approaches (caudal, S1 foraminal, and L5-S1 transforaminal) used to
      treat PLSS. STUDY DESIGN: This study used a case control, blind study. SETTING:
      The research took place at the pain clinic and interventional pain practice room
      at Asyut University Hospital, Assiut, Egypt. METHODS: Sixty consecutive PLSS
      patients were recruited and randomized into 3 groups (caudal, S1 foraminal, and
      L5-S1 transforaminal) before receiving adhesiolysis and neuroplasty. All patients
      underwent nerve conduction studies and magnetic resonance imaging (MRI). Pain
      severity levels were assessed and measured using the Oswestry Disability
      Questionnaire (OSW) and the Visual Analog Scale (VAS). Patient satisfaction was
      evaluated using a Likert scale. The first assessment was performed prior to the
      procedure to determine the patients' baseline levels of pain severity. Follow-up
      assessments were performed 1-, 3-, and 6-months after the procedure. RESULTS:
      Results of the group pairwise analysis indicated that, relative to baseline,
      there were significant decreases in pain relief scores (VAS and OWS) and
      functional assessment expressed by patients' satisfaction across all time
      intervals and in all 3 groups (P < 0.01). Conversely, a between group analysis
      revealed that VAS, OWS, and patient satisfaction scores were comparable across
      the 3 groups at all time intervals (P > 0.05). There were no differences in rates
      of complications between the 3 different groups. LIMITATIONS: Our study was
      limited by the low number of patients and the short duration (6 months) of follow
      up. CONCLUSION: The 3 anatomical approaches (caudal, S1 foraminal, and L5-S1
      transforaminal) result in the same outcome with regard to pain relief and
      complication rate. KEY WORDS: Post lumber surgery syndrome, post laminectomy back
      pain, percutaneous adhesiolysis, Racz catheter, percutaneous neuroplasty.

PMID- 30282399
TI  - Enhanced Pain Sensitivity with Systemic Ultrastructural Changes of the Nervous
      Systems after Cobra Venom Injection is Reversed by Electroacupuncture Treatment.
AB  - BACKGROUND: Electroacupuncture (EA) has been proved to be effective in treating
      certain neuropathic pain conditions. The mechanisms of pain relief by EA are not
      fully understood. There have been sporadic reports of damage in the peripheral
      nervous system (PNS) and regions of the central nervous system (CNS) at the
      ultrastructural level following peripheral nerve injury. However, information
      about possible systemic changes in the PNS and CNS after nerve injury is scarce.
      OBJECTIVES: The goal of this study was to examine the ultrastructural changes of
      the nervous system induced by a local injection of cobra venom into the sciatic
      nerve and to compare the ultrastructural changes in rats with or without
      treatment with EA or pregabalin. STUDY DESIGN: An experimental study. SETTING:
      Department of Anesthesiology, Pain Medicine, and Critical Care Medicine, Aviation
      General Hospital of China Medical University. METHODS: In this study, using an
      established model of sciatic neuralgia induced by local injection of cobra venom
      into the sciatic nerve, we examined ultrastructural changes of the PNS and CNS
      and how they respond to EA and pregabalin treatment. EA and pregabalin were given
      daily from postoperative day (POD) 14 to 36. Based on previous works, the
      frequency of EA stimulation of the ST36 and GB34 acupoints was held to 2/100 Hz
      variable. Pain sensitivity in the sciatic neuralgia rats with and without
      treatments was assessed using the von Frey test. Ultrastructural alterations were
      examined bilaterally in the prefrontal cortex, hippocampus, medulla oblongata;
      and the cervical, thoracic, and lumbar spinal cords on PODs 14, 40, and 60.
      Ultrastructural examinations were also carried out on the bilateral sciatic
      nerves and dorsal root ganglion (DRG) at the cervical, thoracic and lumbar
      levels. In rats treated with EA or pregabalin, the ultrastructure was examined on
      PODs 40 and 60. RESULTS: Behavioral signs of pain and systemic ultrastructural
      changes including demyelination were observed at all levels of the PNS and CNS in
      rats with sciatic neuralgia. After intervention, the mechanical withdrawal
      thresholds of the EA group and pregabalin group were significantly higher than
      that of the cobra venom group (P < 0.05). Both EA and pregabalin treatments
      partially reversed increased cutaneous sensitivity to mechanical stimulation.
      However, only the EA treatment was able to repair the ultrastructural damages
      caused by cobra venom. LIMITATIONS: The results confirm that peripheral nerve
      injury led to the ultrastructural damage at different levels of the CNS as
      demonstrated with electron microscopy; however, we need to further verify this at
      both the molecular level and in light microscope level. Sciatic neuralgia induced
      by cobra venom is a chemical injury, and whether this exactly mimics a peripheral
      nerve mechanical injury is still unclear. CONCLUSIONS: Local cobra venom
      injection leads to systemic neurotoxicity. EA and pregabalin alleviate pain via
      different mechanisms. KEY WORDS: Sciatic neuralgia, cobra venom, demyelination,
      electroacupuncture, pregabalin, rat model.

PMID- 30282400
TI  - Ionizing Radiation Dose Exposure to the Ocular Region of Pain Physicians During C
      arm Guided Pain Interventions.
AB  - BACKGROUND: The growth of interventional pain medicine in recent years has
      resulted in more procedures being carried out under fluoroscopic guidance. The
      proximity of the pain physician (PP) to ionization radiation (IR) potentially
      increases the risk of radiation exposure to the ocular region. A European
      directive has reduced the limits of occupational ocular dose 7.5-fold.
      OBJECTIVES: The objectives of this study are to quantify the typical IR exposure
      in the ocular region of PP and to compare it to recommended international
      guidelines. STUDY DESIGN: Three consultants involved in the pain unit service
      were enrolled in the study to reflect the dose implications involved with
      different caseloads, training obligations, and procedure types. All 3 consultants
      were experienced primary operators. SETTING: The study was undertaken at the pain
      management suite in the South Infirmary Victoria University Hospital (SIVUH).
      Annually, this unit performs 2,800 fluoroscopic guide pain procedures. METHODS:
      Thermoluminescent dosimeters (TLDs) calibrated to measure eye lens doses [Hp
      (0.07)] and whole-body doses (WBDs) were fitted to 3 pain consultants while they
      undertook imaging-guided pain procedures using mobile C-arm fluoroscopy over a 3
      month period. The duration of radiation exposure, screening time (seconds), and
      procedure type were recorded. Radiation dose was calculated to estimate the
      effective radiation dose to the ocular region using (i) dose-area product (DAP)
      in milliGray per centimeter squared (mGycm2) and (ii) Air Kerma (AK) values in
      mGy. RESULTS: IR doses were effectively recorded in 682 cases over 3 months and
      the data extrapolated. The estimated annual lens dose experienced by pain
      physicians performing fluoroscopy-guided procedures is less than the recommended
      international guidelines. A significant linear relationship between screening
      time and IR exposure was estimated (rs = 0.93, P < 0.01). LIMITATIONS: In many
      centers, including our own, fluoroscopy procedures are undertaken by
      nonconsultant staff. Therefore, a small single-center cohort recruiting
      experienced consultant staff and not including pain fellows or
      registrars/residents with varying levels of experience is a limitation.
      CONCLUSION: While IR to the ocular region was significantly less than the
      recommended European safety guidelines, the annual dose needs to be confirmed in
      pain physicians with a lesser degree of clinical experience. KEY WORDS: Ionizing
      radiation, ocular, radiation protection, pain medicine, interventional.

PMID- 30282401
TI  - Patients' Perceptions of Chronic Pain During the Economic Crisis: Lessons Learned
      from Greece.
AB  - BACKGROUND: Chronic pain is well known to be influenced by various social
      factors; however, the impact of financial issues on pain has not been extensively
      studied. OBJECTIVE: The aim of this study was to investigate the impact of the
      economic crisis on pain and quality of life in Greek patients suffering from
      chronic pain. STUDY DESIGN: The study employed a prospective, open-label design.
      SETTING: The study setting was the Pain Unit of Attikon University Hospital in
      Athens, Greece. METHODS: The study surveyed 200 randomly selected outpatients
      with chronic pain during two different time periods (2012 and 2016). Patients
      completed a structured questionnaire to assess the impact of the economic crisis
      on multiple aspects of pain and pain management, health care, and quality of
      life. Personality characteristics and stress were also evaluated using the DASS
      42 and the LOT-R questionnaires. RESULTS: Most patients in both periods believed
      that the economic crisis led to a worsening of their symptoms (75%) and quality
      of life (97%). Most patients (97.5%) also believed that the intensity of their
      pain would have been improved if their financial status had been better. Their
      main concerns about the future were "the possibility of not having access to
      health care facilities and medication" (94.5%), "stress" (43%), and "fear of
      financial strain" (30.5%). Higher levels of anxiety, stress, and pessimism were
      associated with higher levels of pain and lower quality of life. LIMITATIONS: The
      study is based on a small sample size. CONCLUSIONS: This study identified impacts
      of the financial crisis on chronic pain and quality of life, pointing to the need
      for measures to solve this problem. KEY WORDS: Pain, global financial crisis,
      quality of life, quality of health care, psychosocial factors.

PMID- 30282402
TI  - Combination of Pulsed Radiofrequency with Continuous Radiofrequency
      Thermocoagulation at Low Temperature Improves Efficacy and Safety in V2/V3
      Primary Trigeminal Neuralgia.
AB  - BACKGROUND: Primary trigeminal neuralgia (TN) is a common clinical refractory
      neuralgia. Severe pain is experienced during episodes, severely impacting the
      patient's quality of life. Long-term suffering from the disease can lead to
      anxiety, depression, and even suicide. The pathological processes involved in TN
      are complex, the mechanisms of pathogenesis are unknown, and effective treatment
      is lacking. OBJECTIVE: This study aimed to assess the efficacy and safety of
      computed tomography (CT)-guided pulsed radiofrequency (PRF) combined with low
      temperature continuous radiofrequency (CRF) thermocoagulation in V2/V3 primary
      trigeminal neuralgia. STUDY DESIGN: This research used a retrospective
      comparative study design. SETTING: The research took place at Shengjing Hospital
      of China Medical University. METHODS: A total of 80 hospitalized patients with TN
      were selected between January 2014 and December 2015 and randomly assigned to 2
      groups differentiated by therapeutic method: CRF (CRF group, n = 40) and PRF +
      CRF (PCRF group, n = 40). Radiofrequency therapy was performed under the guidance
      of CT. Follow-up measures assessed preoperative conditions, pain remission,
      complications and side effects, recovery time, and recurrence rate over the 2
      years following the surgery. RESULTS: The Visual Analog Scale (VAS) scores
      decreased in both groups after surgery. After one month, the decrease in the VAS
      score in the PCRF group was more apparent, and this difference was maintained for
      2 years. The total efficiency rates in the CRF and PCRF groups were 85% and
      97.5%, respectively, at 6 months, 1 year, and 2 years post-surgery. The
      differences in total efficiency rate of pain between the 2 groups at 6 months, 1
      year, and 2 years were statistically significant. Recovery times in the PCRF
      group were shorter than those in the CRF group. Specifically, recovery times for
      facial numbness in the CRF and PCRF groups were 3.12 +/- 1.21 months and 2.23 +/-
      1.02 months, respectively. Recovery times for masticatory muscle weakness were
      4.33 +/- 1.54 months and 3.42 +/- 0.98 months, respectively. LIMITATIONS: This
      study is limited by being a retrospective study, and by having a relatively small
      sample size from a single center. CONCLUSIONS: CT-guided PRF combined with low
      temperature CRF thermocoagulation for treating V2/V3 primary TN effectively
      relieves pain, increases late-stage pain remission rate, reduces complications,
      and reduces the rate of recurrence. KEY WORDS: Complication, continuous
      radiofrequency thermocoagulation, pulsed radiofrequency, recurrence rate,
      trigeminal neuralgia, Visual Analog Scale.

PMID- 30282403
TI  - Contribution of Spinal PKCgamma Expression to Short- and Long-lasting Pain
      Behaviors in Formalin-induced Inflamed Mice.
AB  - BACKGROUND: Over-expression of spinal protein kinase Cgamma(PKCgamma) contributes
      to the induction of persistent bilateral hyperalgesia following inflammatory
      injury, yet the role of spinal PKCgamma in short- and long-lasting pain behavior
      is poorly understood. OBJECTIVE: This study aimed to characterize the
      contribution of spinal PKCgamma to spontaneous pain and long-lasting bilateral
      hyperalgesia in formalin-induced inflamed mice using pharmacological inhibition.
      STUDY DESIGN: Laboratory animal study. SETTING: The study was performed in the
      Department of Human Anatomy and K.K. Leung Brain Research Centre, Preclinical
      School of Medicine, the Fourth Military Medical University (Xi'an, China) and the
      Department of Anesthesiology, Fuzhou General Hospital (Fuzhou, China). METHODS:
      Male mice were unilaterally intraplantarly injected with formalin to induce
      inflammatory pain. Spontaneous pain behaviors, including flinches and lickings,
      were recorded by off-line video during the first hour post-injection and counted.
      Using von Frey tests, long-lasting bilateral mechanical paw withdrawal thresholds
      were determined before injection and at indicated time points thereafter.
      Temporal expression of spinal PKCgamma was observed by immunohistochemical
      staining. For pharmacological inhibition, mice were treated daily with
      intrathecal Tat carrier or selective PKCgamma inhibitor KIG31-1, from 1 hour
      prior to 10 days after formalin injection. Spontaneous pain behaviors and long
      lasting bilateral mechanical hyperalgesia were assessed. Spinal PKCgamma
      expression was also observed by using immunohistochemical staining and western
      blot. RESULTS: The number of PKCgamma-immunoreactive (ir) spinal neurons was
      significantly higher at 10 days, but not 2 hours, after formalin intraplantar
      injection, and accompanied by long-lasting bilateral hyperalgesia. Furthermore,
      long-lasting bilateral hyperalgesia could be reversed by pharmacological
      inhibition of over-expressed spinal PKCgamma; however, pretreating with
      intrathecal KIG31-1 showed no antinociceptive effects on short-term spontaneous
      pain behaviors. LIMITATIONS: All results were obtained from the mice and no
      PKCgamma inhibitors were available through clinical practice. Therefore, it
      remains difficult to draw definitive connections between animal research and
      human application. CONCLUSION: Our findings suggest that spinal PKCgamma plays a
      predominant role in long-lasting bilateral hyperalgesia, but not in the
      spontaneous pain behaviors induced by formalin. KEY WORDS: Formalin, spontaneous
      pain, mechanical hyperalgesia, protein kinase C gamma, KIG31-1, mice.

PMID- 30282404
TI  - Feasibility of Percutaneous Robot-Assisted Epiduroscopic System.
AB  - BACKGROUND: Endoscopy has replaced open surgery, especially in spinal surgery.
      Among them, image-guided epiduroscopy allows pain generators to be identified,
      including epidural adhesion, fibrotic tissues, root compression, and spinal
      stenosis. However, the heavy lead apron worn by pain physicians to avoid exposure
      to radiation can induce occupational hazards, such as orthopedic complications
      and radiation-induced cancer. Hence, we developed a robotic system to address
      these problems. OBJECTIVE: The aim of the study was to evaluate the feasibility
      of a robot-controlled epiduroscopic system. STUDY DESIGN: In vivo animal
      experiment. SETTING: University in Republic of Korea. METHODS: The robot
      controlled epiduroscopic system was developed using the open architecture robot
      system (The Raven Surgical Robotic System, CITRIS, Berkley, CA, USA). The robotic
      system consists of a lab-made epiduroscope, steering section, robotic arm, and
      manipulator. For the in vivo study, 2 Yorkshire pigs were used to simulate an
      epiduroscopic procedure with the robotic system. RESULTS: The insertion and
      steering of the catheter was performed safely, and epiduroscopic visualization
      was obtained without side effects. There were no device-related complications.
      Radiation exposure for the primary operator was 80% lower than the levels found
      during conventional epiduroscopic procedures. All live pigs showed normal
      behavior without any signs of pain. The mean time to reach the target region was
      less than 8 minutes. LIMITATIONS: The epiduroscopic procedure was performed on
      pigs and not on humans. The dimensions of the spinal canal of pigs cannot compare
      to those of humans. CONCLUSIONS: We demonstrated the feasibility of the robot
      assisted epiduroscopic system. KEY WORDS: Epiduroscopy, robotic system, spine,
      pig, animal model.

PMID- 30282405
TI  - Mexiletine Usage in a Chronic Pain Clinic: Indications, Tolerability, and Side
      Effects.
AB  - BACKGROUND: Intravenous lidocaine has multiple applications in the management of
      acute and chronic pain. Mexiletine, an oral lidocaine analogue, has been used in
      a number of chronic pain conditions although its use is not well characterized.
      OBJECTIVES: To report our experience using mexiletine in a chronic pain
      population, specifically looking at tolerability, side effects, and EKG changes.
      STUDY DESIGN: Retrospective, cohort study. SETTING: Three chronic pain clinics
      within a hospital system in Detroit, MI. METHODS: All patients who had a
      mexiletine prescription between August 2015 and August 2016 were queried via the
      electronic medical record. Each chart was examined for demographics, QTc changes
      on EKG, length of use, and reasons for stoppage. RESULTS: There were 74 total
      patients identified in the chronic pain management clinics as receiving at least
      1 mexiletine prescription over the 1-year time period. Twice as many women as men
      received mexiletine prescriptions. Neuropathic pain was the most common primary
      diagnosis (64%) which included diabetic neuropathy, radiculopathy, and others.
      Fibromyalgia was the next most common primary diagnosis (28%). A QTc change on
      the EKG showed a mean decrease of 0.1 ms and median increase of 1.5 ms. At 6
      months (180 days), approximately 30% of the patients remained on mexiletine
      therapy, and 28% remained on the therapy at 1 year (360 days). Median duration of
      use was 60 days and the mean was 288 days. Neurologic and gastrointestinal side
      effects were the most commons reason for stoppage. All side effects were mild and
      resolved with stoppage. After side effects, lack of response, or loss of
      efficacy, were the next most common reasons for stoppage. LIMITATIONS: Pain
      relief and outcomes were not specifically examined due to confounding factors
      including interventional treatments and multiple treatment modalities. This was a
      retrospective, cohort study limited to our specific clinic population with a
      relatively high loss to follow-up rate. CONCLUSION: Mexiletine is rarely a first
      line option for chronic pain management and is often used when multiple other
      modalities have failed. By reporting our experience, we hope other clinicians may
      have more familiarity with the drug's use in a chronic pain practice. It appears
      reasonably tolerable, may not require frequent EKG monitoring, and can be an
      appropriate adjunct in the chronic pain population. More research is needed
      regarding efficacy and dose titration for mexiletine in chronic pain. KEY WORDS:
      Chronic pain, mexiletine, IV lidocaine, pain, neuropathic pain, neuropathy,
      fibromyalgia, QTc, tolerability.

PMID- 30282406
TI  - Re: Neuropathic Pain in Acute and Subacute Neuropathies: A Systematic Review.

PMID- 30282407
TI  - In the article " Effect of addition of epidural ketamine to steroid in lumbar
      radiculitis: One - Year Follow-Up," published in Pain Physician journal in
      September/ October 2011; 14:475- 481.

PMID- 30282408
TI  - Thinking about Descartes' rules when writing a paper.

PMID- 30282409
TI  - Current status of simulation training in plastic surgery residency programs: A
      review.
AB  - Increased emphasis on competency-based learning modules and widespread departure
      from traditional models of Halstedian apprenticeship have made surgical
      simulation an increasingly appealing component of medical education. Surgical
      simulators are available in numerous modalities, including virtual, synthetic,
      animal, and non-living models. The ideal surgical simulator would facilitate the
      acquisition and refinement of surgical skills prior to clinical application, by
      mimicking the size, color, texture, recoil, and environment of the operating
      room. Simulation training has proven helpful for advancing specific surgical
      skills and techniques, aiding in early and late resident learning curves. In this
      review, the current applications and potential benefits of incorporating
      simulation-based surgical training into residency curriculum are explored in
      depth, specifically in the context of plastic surgery. Despite the prevalence of
      simulation-based training models, there is a paucity of research on integration
      into resident programs. Current curriculums emphasize the ability to identify
      anatomical landmarks and procedural steps through virtual simulation. Although
      transfer of these skills to the operating room is promising, careful attention
      must be paid to mastery versus memorization. In the authors' opinions,
      curriculums should involve step-wise employment of diverse models in different
      stages of training to assess milestones. To date, the simulation of tactile
      experience that is reminiscent of real-time clinical scenarios remains
      challenging, and a sophisticated model has yet to be established.

PMID- 30282411
TI  - Accessory auricle: Classification according to location, protrusion pattern and
      body shape.
AB  - BACKGROUND: Accessory auricles (AAs) are common congenital anomalies. We present
      a new classification according to location and shape, and propose a system for
      coding the classifications. METHODS: This study was conducted by reviewing the
      records of 502 patients who underwent surgery for AA. AAs were classified into
      three anatomical types: intraauricular, preauricular, and buccal. Intraauricular
      AAs were divided into three subtypes: intracrural, intratragal, and intralobal.
      Preauricular AAs were divided into five subtypes: precrural, superior pretragal,
      middle pretragal, inferior pretragal, and prelobal. Buccal AAs were divided into
      two subtypes: anterior buccal and posterior buccal. AAs were also classified
      according to their protrusion pattern above the surrounding surface:
      pedunculated, sessile, areolar, remnant, and depressed. Pedunculated and sessile
      AAs were subclassified as spherical, ovoid, lobed, and nodular, according to
      their body shape. Cartilage root presence and family history of AA were reviewed.
      A coding system for these classifications was also proposed. RESULTS: The total
      number of AAs in the 502 patients was 1,003. Among the locations, the superior
      pretragal subtype (27.6%) was the most common. Among the protrusion patterns and
      shapes, pedunculated ovoid AAs were the most common in the preauricular (27.8%)
      and buccal areas (28.0%), and sessile lobed AAs were the most common in the
      intraauricular area (48.7%). The proportion of AAs with a cartilage root was
      78.4%, and 11% of patients had a family history. The most common type of
      preauricular AA was the superior pretragal pedunculated ovoid AA (13.2%) with a
      cartilage root. CONCLUSIONS: This new system will serve as a guideline for
      classifying and coding AAs.

PMID- 30282410
TI  - Development of an easy-to-handle murine model for the characterization of
      radiation-induced gross and molecular changes in skin.
AB  - BACKGROUND: Radiation-induced skin injury is a dose-limiting complication of
      radiotherapy. To investigate this problem and to develop a framework for making
      decisions on treatment and dose prescription, a murine model of radiation-induced
      skin injury was developed. METHODS: The dorsal skin of the mice was isolated, and
      irradiation was applied at single doses of 15, 30, and 50 Gy. The mice were
      followed for 12 weeks with serial photography and laser Doppler analysis.
      Sequential skin biopsy samples were obtained and subjected to a histological
      analysis, immunostaining against transforming growth factor beta (TGF-beta), and
      Western blotting with Wnt-3 and beta-catenin. Increases in the levels of TGF
      beta, Wnt, and beta-catenin were detected after irradiation. RESULTS: All tested
      radiation doses caused progressive dermal thickening and fibrosis. The cause of
      this process, however, may not be radiation alone, as the natural course of wound
      healing may elicit a similar response. The latent appearance of molecular and
      histological markers that induce fibrosis in the 15 Gy group without causing
      apparent gross skin injuries indicates that 15 Gy is an appropriate dose for
      characterizing the effects of chronic irradiation alone. Thus, this model best
      mimics the patterns of injury that occur in human subjects. CONCLUSIONS: This
      animal model can be used to elucidate the gross and molecular changes that occur
      in radiation-induced skin injury and provides an effective platform for studying
      this adverse effect without complicating the process of wound healing.

PMID- 30282412
TI  - National perioperative outcomes of flap coverage for pressure ulcers from 2005 to
      2015 using American College of Surgeons National Surgical Quality Improvement
      Program.
AB  - BACKGROUND: Complication rates after flap coverage for pressure ulcers have been
      high historically. These patients have multiple risk factors associated with poor
      wound healing and complications including marginal nutritional status, prolonged
      immobilization, and a high comorbidities index. This study utilizes the National
      Surgical Quality Improvement Program (NSQIP) to examine perioperative outcomes of
      flap coverage for pressure ulcers. METHODS: Data from the NSQIP database (2005
      2015) for patient undergoing flap coverage for pressure ulcers was identified.
      Demographic, perioperative information, and complications were reviewed. One-way
      analysis of variance and Pearson chi-square were used to assess differences for
      continuous variables and nominal variables, respectively. Multivariate logistic
      regression was performed to identify independent risk factors for complications.
      RESULTS: There were 755 cases identified: 365 (48.3%) sacral ulcers, 321 (42.5%)
      ischial ulcers, and 69 (9.1%) trochanteric ulcers. Most patients were older male,
      with some degree of dependency, neurosensory impairment, high functional
      comorbidities score, and American Society of Anesthesiologists class 3 or above.
      The sacral ulcer group had the highest incidence of septic shock and bleeding,
      while the trochanteric ulcer group had the highest incidence of superficial
      surgical site infection. There was an overall complication rate of 25% at 30-day
      followup. There was no statistical difference in overall complication among
      groups. Total operating time, diabetes, and non-elective case were independent
      risk factors for overall complications. CONCLUSIONS: Despite patients with poor
      baseline functional status, flap coverage for pressure ulcer patients is safe
      with acceptable postoperative complications. This type of treatment should be
      considered for properly selected patients.

PMID- 30282413
TI  - Location of the umbilicus in Korean women and its changes after breast
      reconstruction with an ipsilateral pedicled rectus abdominis musculocutaneous
      flap.
AB  - BACKGROUND: The umbilicus makes an important contribution to the natural
      appearance of the abdomen. To date, studies on its position in Korean women are
      lacking, and no standards have been established. The purpose of this study was to
      investigate the position of umbilicus in Korean women and to review changes in
      its position after ipsilateral pedicled rectus abdominis musculocutaneous (IP
      RAM) flap. METHODS: This research consisted of two studies. In first study, 100
      females who visited the emergency department with gastroenteritis between 2007
      and 2011 were included. In second study, 40 women who underwent IP-RAM flap in
      the same period were included. Using abdominal computed tomography, we measured
      the distance between xiphoid process and umbilicus, represented by value a, and
      the distance between umbilicus and symphysis pubis, represented by value b. Thus,
      the location of the umbilicus was represented by the ratio a/b. The data were
      analyzed using Pearson correlation test and paired t-test. RESULTS: In study 1,
      the mean value of a/b was 1.07. Pearson correlation test revealed a significant
      correlation between age and a/b. In study 2, the mean value of a/b was 1.16 in
      preoperative measurements and 1.01 in postoperative measurements. The paired t
      test showed a significant difference between preoperative and postoperative
      measurements, indicating cephalic migration of the umbilicus after surgery.
      CONCLUSIONS: The natural position of the umbilicus showed caudal migration with
      aging. Additionally, in a comparison of preoperative and postoperative
      measurements in patients who underwent IP-RAM flap, cephalic migration of the
      umbilicus was observed after surgery.

PMID- 30282414
TI  - Impact of hormonal therapy and other adjuvant therapies on contralateral breast
      volume change after implant-based breast reconstruction.
AB  - BACKGROUND: Adjuvant therapy after breast surgery, including tamoxifen or
      aromatase inhibitors, improves the postoperative outcomes and long-term survival
      of breast cancer patients. The aim of this study was to determine whether volume
      changes occurred in the contralateral breast during hormonal or other adjuvant
      therapies. METHODS: This study reviewed 90 patients who underwent unilateral
      breast reconstruction between September 2012 and April 2018 using tissue
      expanders and a permanent implant after the surgical removal of breast cancer.
      The volume of the contralateral breast was measured using a cast before the first
      (tissue expander insertion) and second (permanent implant change) stages of
      surgery. Changes in breast volume were evaluated to determine whether adjuvant
      therapy such as hormonal therapy, chemotherapy, and radiation therapy influenced
      the volume of the contralateral breast. RESULTS: The group receiving tamoxifen
      therapy demonstrated a significant decrease in volume compared with the group
      without tamoxifen (-7.8% vs. 1.0%; P=0.028). The aromatase inhibitor-treated
      group showed a significant increase in volume compared with those who did not
      receive therapy (-6.2% vs. 4.5%; P=0.023). There were no significant differences
      between groups treated with other hormonal therapy, chemotherapy, or radiation
      therapy. CONCLUSIONS: Patients who received tamoxifen therapy showed a
      significant decrease in volume in the contralateral breast, while no significant
      change in weight or body mass index was found. Our findings suggest that we
      should choose smaller implants for premenopausal patients, who have a high
      likelihood of receiving tamoxifen therapy.

PMID- 30282415
TI  - Breast reconstruction statistics in Korea from the Big Data Hub of the Health
      Insurance Review and Assessment Service.
AB  - BACKGROUND: Previously, surveys have been used to investigate breast
      reconstruction statistics. Since 2015, breast reconstruction surgery after
      mastectomy has been covered by the National Health Insurance Service in Korea,
      and data from breast reconstruction patients are now available from the Health
      Insurance Review and Assessment Service (HIRA). We investigated statistics in
      breast reconstruction in Korea through statistics provided by the HIRA Big Data
      Hub. METHODS: We investigated the number of cases in mastectomy and breast
      reconstruction methods from April 1, 2015 to December 31, 2016. Data were
      furnished by the HIRA Big Data Hub and accessed remotely online. Results were
      tabulated using SAS Enterprise version 6.1. RESULTS: The 31,155 mastectomy cases
      included 7,088 breast reconstruction cases. Implantbased methods were used in
      4,702 cases, and autologous methods in 2,386. The implantbased reconstructions
      included 1,896 direct-to-implant and 2,806 tissue-expander (2-stage) breast
      reconstructions. The 2-stage tissue-expander reconstructions included 1,624
      expander insertions (first stage) and 1,182 expander-to-permanent-implant
      exchanges (second stage). Of the autologous breast reconstructions, 705 involved
      latissimus dorsi muscle flaps, 498 involved pedicled transverse rectus abdominis
      myocutaneous (TRAM) flaps, and 1,183 involved free-tissue transfer TRAM flaps,
      including deep inferior epigastric perforator free-tissue transfer flaps. There
      were 1,707 nipple-areolar complex reconstructions, including 1,565 nipple
      reconstructions and 142 areola reconstructions. The 1-year mean number of breast
      reconstructions was 4,050. CONCLUSIONS: This was the first attempt to evaluate
      the total number of breast reconstruction procedures using accurate,
      comprehensive data, and our findings may prove valuable as a foundation for
      future statistical studies of breast reconstruction procedures in Korea.

PMID- 30282416
TI  - Incorporating a continuous suction system as a preventive measure against fistula
      related complications in head and neck reconstructive surgery.
AB  - BACKGROUND: Although previous studies have focused on determining prognostic and
      causative variables associated with fistula-related complications after head and
      neck reconstructive surgery, only a few studies have addressed preventive
      measures. Noting that pooled saliva complicates wound healing and precipitates
      fistula-related complications, we devised a continuous suction system to remove
      saliva during early postoperative recovery. METHODS: A continuous suction system
      was implemented in 20 patients after head and neck reconstructive surgery between
      January 2012 and October 2017. This group was compared to a control group of 16
      patients at the same institution. The system was placed orally when the lesion
      was on the anterior side of the retromolar trigone area, and when glossectomy or
      resection of the mouth floor was performed. When the orohypopharynx and/or larynx
      were eradicated, the irrigation system was placed in the pharyngeal area.
      RESULTS: The mean follow-up period was 9.2+/-2.4 months. The Hemovac system was
      applied for an average of 7.5 days. On average, 6.5 days were needed for the net
      drain output to fall below 10 mL. Complications were analyzed according to their
      causes and rates. A fistula occurred in two cases in the suction group. Compared
      to the control group, a significant difference was noted in the surgical site
      infection rate (P<0.031). CONCLUSIONS: Clinical observations showed reduced
      saliva pooling and a reduction in the infection rate. This resulted in improved
      wound healing through the application of a continuous suction system.

PMID- 30282417
TI  - Volar plate avulsion fracture alone or concomitant with collateral ligament
      rupture of the proximal interphalangeal joint: A comparison of surgical outcomes.
AB  - BACKGROUND: Volar plate avulsion fracture of the proximal interphalangeal (PIP)
      joint is one of the most common hand injuries. In this study, we divided patients
      into two groups: patients with pure volar plate avulsion fracture, and patients
      with volar plate avulsion fracture concomitant with collateral ligament rupture.
      The purpose of this study was to compare long-term surgical outcomes between the
      two groups. As a secondary measure, the Mitek bone anchoring and polydioxanone
      (PDS) bone suturing techniques were compared. METHODS: A single-institutional
      retrospective review of the surgical treatment of volar plate avulsion fracture
      was performed. The cases were divided into those with pure volar plate avulsion
      fracture (group A, n=15) and those with volar plate avulsion fracture concomitant
      with collateral ligament rupture (group B, n=15). Both groups underwent volar
      plate reattachment using Mitek bone anchoring or PDS bone suturing followed by 2
      weeks of immobilization in a dorsal protective splint. RESULTS: The average range
      of motion of the PIP joint and extension lag were significantly more favorable in
      group A (P<0.05). Differences in age; follow-up period; flexion function; visual
      analog scale scores; disabilities of the arm, shoulder, and hand scores; and the
      grip strength ratio between the two groups were non-significant. No significant
      differences were found in the surgical outcomes of Mitek bone anchoring and PDS
      bone suturing in group A. CONCLUSIONS: Overall, the surgical outcomes of volar
      plate reattachment were successful irrespective of whether the collateral
      ligaments were torn. However, greater extension lag was observed in cases of
      collateral ligament injury.

PMID- 30282418
TI  - Use of a helical composite free flap for alar defect reconstruction with a
      supermicrosurgical technique.
AB  - The highly contoured nature of the nose and the abundant free margin makes it
      especially difficult to reconstruct. In this report, we describe the use of a new
      helical rim free flap technique for the reconstruction of full-thickness nasal
      alar defects via supermicrosurgery. Briefly, after a wide excision with a margin
      of 0.7 cm, an alar defect with a size of 1*1*0.5cm was obtained, which included
      the full thickness of the skin, mucosa, and lower lateral cartilage. Vessel
      dissection was performed in a straightforward manner, starting from the incision
      margin for flap harvest, without any further dissection for reach the greater
      trunk of the superficial temporal artery. The flap was inset in order to match
      the contour of the contralateral ala. We closed the donor site via rotation and
      advancement. No donor site morbidity was observed, despite the presence of a
      small scar that could easily be covered with hair. The alar contour was
      satisfactory, and the patient was satisfied with the results. The
      supermicrosurgical technique did not require further dissection to identify the
      vessels for anastomosis, leading to better cosmetic outcomes and a reduced
      operating time.

PMID- 30282419
TI  - Mechanical irritation by protruding bone: A possible cause of breast implant
      rupture.
AB  - Although breast implants have been in clinical use for almost 6 decades and have
      undergone considerable development during this time, implant rupture is still a
      dreaded long-term complication. Some obvious external factors, such as trauma,
      can lead to implant rupture, but many studies have reported a high rate of
      "spontaneous" implant rupture. Herein, we present two cases with the aim of
      raising awareness of a new possible cause of "spontaneous" implant rupture:
      mechanical irritation by bony protrusions.

PMID- 30282420
TI  - Recurrent carpal tunnel syndrome associated with extension of flexor digitorum
      muscle bellies into the carpal tunnel: A case series.
AB  - While the success or failure of carpal tunnel release ultimately depends on the
      interplay of a wide array of factors, a broad understanding of the normal anatomy
      of the carpal tunnel accompanied by awareness of the possible variations of the
      individual structures that make up its contents is crucial to optimizing surgical
      outcomes. While anatomic variants such as extension of the flexor digitorum
      muscle bellies have been described as a cause of primary carpal tunnel syndrome
      (CTS), there have been no reports depicting its association with recurrent CTS
      following initially successful carpal tunnel release, a finding with potentially
      significant prognostic implications that can aid in operative planning. In such
      cases where muscle extension is identified preoperatively, careful debulking of
      the muscle belly may be beneficial in improving long-term surgical outcomes.

PMID- 30282421
TI  - Simultaneous reconstruction of the forearm extensor compartment tendon, soft
      tissue, and skin.
AB  - Malignant peripheral nerve sheath tumor (MPNST) is a very rare type of sarcoma,
      with an incidence of 0.001%. MPNST has a 5-year survival rate near 80%, so
      successful reconstruction techniques are important to ensure the patient's
      quality of life. Sarcoma of the forearm is known for its poor prognosis, which
      leads to wider excision, making reconstruction even more challenging due to the
      unique anatomical structure and delicate function of the forearm. A 44-year-old
      male presented with a large mass that had two aspects, measuring 9*6 cm and 7*5
      cm, on the dorsal aspect of the right forearm. The extensor compartment muscles
      (EDM, EDC, EIP, EPB, EPL, ECRB, ECRL, APL) and invaded radius were resected with
      the mass. Tendon transfer of the entire extensor compartment with skin defect
      coverage using a 24*8 cm anterolateral thigh (ALT) perforator free flap was
      performed. The patient was discharged after 18 days without wound complications,
      and has not complained of discomfort during supination, pronation, or wrist
      extension/flexion through 3 years of follow-up. To our knowledge, this is the
      first report of successful reconstruction of the entire forearm extensor
      compartment with ALT free flap coverage after resection of MPNST.

PMID- 30282422
TI  - A novel technique for large and ptotic breast reconstruction using a latissimus
      dorsi myocutaneous flap set at the posterior aspect, combined with a silicone
      implant, following tissue expander surgery.
AB  - Large and ptotic breast reconstruction in patients who are not candidates for a
      transverse rectus abdominalis myocutaneous flap and revision surgery for the
      contralateral breast remains challenging. We developed a novel breast
      reconstruction technique using a latissimus dorsi myocutaneous (LD m-c) flap set
      at the posterior aspect of the reconstructed breast, combined with an anatomical
      silicone breast implant (SBI), following tissue expander surgery. We performed
      the proposed technique in four patients, in whom the weight of the resected
      tissue during mastectomy was >500 g and the depth of the inframammary fold (IMF)
      was >3 cm. After over-expansion of the lower portion of the skin envelope by a
      tissue expander, the LD m-c flap was transferred to cover the lower portion of
      the breast defect and to achieve a ptotic contour, with the skin paddle set at
      the posterior aspect of the reconstructed breast. An SBI was then placed in the
      rest of the breast defect after setting the LD m-c flap. No major complications
      were observed during the follow-up period. The proposed technique resulted in
      symmetrical and aesthetically satisfactory breasts with deep IMFs, which allowed
      proper fitting of the brassiere, following large and ptotic breast
      reconstruction.

PMID- 30282423
TI  - An old problem with a new solution: Cost-effective, easy correction of rhinophyma
      using a disposable razor.

PMID- 30282424
TI  - Surgical treatment of velopharyngeal insufficiency.
AB  - Velopharyngeal insufficiency (VPI) is a common complication after primary
      palatoplasty. Although the several surgical treatments of VPI have been
      introduced, there is no consensus guide to select the optimal surgical treatment
      for VPI patients. The selection of surgical treatment for VPI depends on a
      multimodal patient evaluation, such as perceptual speech evaluation, nasometery
      and nasoendoscopy. We can provide more adequate treatment for VPI through the
      deeper understanding of anatomy and physiology in VPI.

PMID- 30282425
TI  - Safety, efficacy, and onset of a novel botulinum toxin type A (Nabota) for the
      treatment of glabellar frown lines: a single-arm, prospective, phase 4 clinical
      study.
AB  - BACKGROUND: Safety, efficacy, and time to onset of effect of botulinum toxin type
      A is of importance to persons who seek improvement in glabellar frown lines, but
      this has not been well studied. The aim of this study was to determine the
      safety, efficacy, and onset of action of a newly developed botulinum toxin type A
      (Nabota) for the treatment of glabellar frown lines. METHODS: This was a single
      arm, open-label, and phase 4 clinical study. Forty-two subjects with glabellar
      lines were treated with five times of intramuscular injection of 0.1 mL (4 U/0.1
      mL) for a total of 20 U of Nabota. Efficacy and safety were assessed at 2, 3, 4,
      5, and 14 days. Efficacy was assessed by the investigator and it was defined as a
      1-point change on a 4-point scale. RESULTS: Improvement in glabellar frown lines
      at maximum frown was observed in 85.4% of subjects 2 days after administration.
      Improvement in glabellar lines at rest was observed in 51.2% of subjects 2 days
      after administration, and the proportion of subjects showing improvement
      increased with time. No severe adverse events were recorded. CONCLUSION: Onset of
      action was observed in the majority of subjects by 2 days after administration of
      Nabota. In addition, Nabota was found to be safe and effective for the treatment
      of glabellar frown lines.

PMID- 30282426
TI  - Use of resorbable mesh and fibrin glue for restoration in comminuted fracture of
      anterior maxillary wall.
AB  - BACKGROUND: The facial bone has a complex structure compared to other bones, and
      various types of fractures can occur due to its characteristics. Among them, in
      comminuted fractures of anterior maxillary wall, multiple depressed and impacted
      bony segments cannot be reduced easily when performing internal fixation using
      plates and screws or wires, and inadequate restoration leads to a range of
      complications. This paper introduces an alternative technique using a resorbable
      mesh with fibrin glue to restore comminuted fractures of anterior maxillary wall.
      METHODS: Thirteen patients were diagnosed with comminuted fractures of anterior
      maxillary wall between March 2017 and February 2018 in the authors' hospital. All
      patients with comminuted fractures of anterior maxillary wall underwent
      restoration using resorbable mesh with fibrin glue. The patients' demographics,
      causes of facial trauma, mean operation time, length of hospital stay, follow-up
      period, and complications were recorded. RESULTS: No major complications and only
      one hypoesthesia of the skin area was noted. Three months after surgery, the
      hypoesthesia recovered completely. After surgery (mean, 3.9 months; range, 2-12
      months), computed tomography showed that the bone fragments in all patients were
      fixed successfully in their anatomical places. CONCLUSION: In comminuted
      fractures of anterior maxillary wall, the use of a resorbable mesh with fibrin
      glue can be an advantageous and effective method for a successful restoration
      without complications.

PMID- 30282427
TI  - Effects of three-dimensionally printed polycaprolactone/beta-tricalcium phosphate
      scaffold on osteogenic differentiation of adipose tissue- and bone marrow-derived
      stem cells.
AB  - BACKGROUND: Autogenous bone grafts have several limitations including donor-site
      problems and insufficient bone volume. To address these limitations, research on
      bone regeneration is being conducted actively. In this study, we investigate the
      effects of a three-dimensionally (3D) printed polycaprolactone (PCL)/tricalcium
      phosphate (TCP) scaffold on the osteogenic differentiation potential of adipose
      tissue-derived stem cells (ADSCs) and bone marrow-derived stem cells (BMSCs).
      METHODS: We investigated the extent of osteogenic differentiation on the first
      and tenth day and fourth week after cell culture. Cytotoxicity of the 3D printed
      PCL/beta-TCP scaffold was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, prior to osteogenic
      differentiation analysis. ADSCs and BMSCs were divided into three groups: C, only
      cultured cells; M, cells cultured in the 3D printed PCL/beta-TCP scaffold; D,
      cells cultured in the 3D printed PCL/beta-TCP scaffold with a bone
      differentiation medium. Alkaline phosphatase (ALP) activity assay, von Kossa
      staining, reverse transcription-polymerase chain reaction (RT-PCR), and Western
      blotting were performed for comparative analysis. RESULTS: ALP assay and von
      Kossa staining revealed that group M had higher levels of osteogenic
      differentiation compared to group C. RT-PCR showed that gene expression was
      higher in group M than in group C, indicating that, compared to group C,
      osteogenic differentiation was more extensive in group M. Expression levels of
      proteins involved in ossification were higher in group M, as per the Western
      blotting results. CONCLUSION: Osteogenic differentiation was increased in
      mesenchymal stromal cells (MSCs) cultured in the 3D printed PCL/TCP scaffold
      compared to the control group. Osteogenic differentiation activity of MSCs
      cultured in the 3D printed PCL/TCP scaffold was lower than that of cells cultured
      on the scaffold in bone differentiation medium. Collectively, these results
      indicate that the 3D printed PCL/TCP scaffold promoted osteogenic differentiation
      of MSCs and may be widely used for bone tissue engineering.

PMID- 30282428
TI  - The effect of the dental root on single mandibular bone fractures.
AB  - BACKGROUND: This study was conducted to determine the effect of the
      distributional relationship between dental roots and the mandibular bone on
      single mandibular bone fractures, which are common craniofacial fractures.
      METHODS: This was a retrospective, single-center study in Seoul, Korea. Patients
      with single mandibular fractures in the symphysis, parasymphysis, body, and angle
      area, with tooth structure involvement were included. The control group included
      patients with simple, bone-level lacerations without fractures. In total, 94
      patients (72 males and 22 females) were included in the treatment group, and 125
      (71 males and 54 females) were included in the control group. The height of the
      mandibular bone and the dental root were measured with panoramic radiography. The
      central incisor represented the symphysis area, the canine represented the
      parasymphysis area, the first molar represented the body area, and the second
      molar represented the angle area. RESULTS: In the treatment group, symphysis
      fractures occurred in 16 patients (17%), parasymphysis fractures in 36 patients
      (38%), body fractures in 17 patients (18%), and angle fractures in 25 patients
      (27%). The ratios of the dental roots to the total height of the mandibular bone
      in the treatment group were 30.35%, 39.75%, 39.53%, and 36.27% for symphysis,
      parasymphysis, body, and angle areas, respectively, whereas in the control group,
      they were 27.73%, 39.70%, 36.76%, and 35.48%. The ratios of the treatment group
      were significantly higher than those of the control group. CONCLUSION: The
      results show that the higher ratio of the dental root to the height of the
      mandibular bone increases the fracture risk.

PMID- 30282429
TI  - A clinical review of reconstructive techniques for patients with multiple skin
      cancers on the face.
AB  - BACKGROUND: Cases of simultaneous multiple skin cancers in a single patient have
      become more common. Due to the multiplicity of lesions, reconstruction in such
      cases is more difficult than after a single lesion is removed. This study
      presents a series of patients with multiple facial skin cancers, with an analysis
      of the surgical removal, reconstruction process, and the results observed during
      follow-up. METHODS: We reviewed 12 patients diagnosed with multiple skin cancers
      on the face between November 2004 and March 2016. The patients' medical records
      were retrospectively reviewed to identify the type of skin cancer, the site of
      onset, methods of surgical removal and reconstruction, complications, and
      recurrence during follow-up. RESULTS: Nine patients had a single type of cancer
      occurring as multiple lesions, while three patients had different skin cancer
      types that occurred together. A total of 30 cancer sites were observed in the 12
      patients. The most common cancer site was the nose. Thirteen defects were
      reconstructed with a flap, while 18 were reconstructed with skin grafting. The
      only complication was one case of recurrence of basal cell carcinoma. CONCLUSION:
      Multiple skin cancers are removed by performing Mohs micrographic surgery or wide
      excision, resulting in multiple defect sites. The authors emphasize the
      importance of thoroughly evaluating local lesions surrounding the initially
      identified lesions or on other sites when reconstructing a large defect which can
      not be covered by primary closure. Furthermore, satisfactory results can be
      obtained by using various methods simultaneously regarding the condition of
      individual patients, the defect site and size, and the surgeon's preference.

PMID- 30282430
TI  - Treatment of fibrous dysplasia of the zygomaticomaxillary complex with radical
      resection and three-dimensional reconstruction with autologous calvarial bone
      graft.
AB  - Fibrous dysplasia (FD) is a rare, benign bone disease with abnormal bone
      maturation and fibroblastic proliferation. Optimal treatment of zone 1
      craniofacial FD is radical resection and reconstruction. To achieve of
      structural, aesthetic, and functional goals, we use three-dimensionally designed
      calvarial bone graft for reconstruction of zygomatic defect after radical
      resection of FD. The authors used a rapid-prototyping model for simulation
      surgery for radical resection and immediate reconstruction. Donor site was
      selected from parietal bone reflect shape, contour, and size of defect. Then
      radical resection of lesion and immediate reconstruction was performed as
      planned. Outcomes were assessed using clinical photographs and computed
      tomography scans. Successful reconstruction after radical resection was achieved
      by three-dimensional calvarial bone graft without complications. After a 12-month
      follow-up, sufficient bone thickness and symmetric soft tissue contour was well
      maintained. By considering three-dimensional configuration of zygomaticomaxillary
      complex, the authors achieved satisfactory structural, aesthetic and functional
      outcomes without complications.

PMID- 30282432
TI  - Sinonasal intestinal-type adenocarcinoma in the frontal sinus.
AB  - Sinonasal intestinal-type adenocarcinoma is a rare neoplasm which can be
      diagnosed by pathologic report. Nasal obstruction, epistaxis, and rhinorrhea are
      common symptoms, but presenting with a benign-looking palpable mass is also
      possible. This is a report of our experience in diagnosing and treating a
      sinonasal intestinal-type low grade adenocarcinoma. A 63-year-old man initially
      presented with a rapidly growing palpable mass in the glabella region for 4
      months. A malignancy of sinus origin was suspected on imaging studies. We
      performed further preoperative evaluations for cancer staging, and curative
      surgery was planned. Radical resection and immediate reconstruction with free
      anterolateral thigh flap were performed. The pathology findings confirmed a
      diagnosis of sinonasal intestinal-type adenocarcinoma.

PMID- 30282431
TI  - Primary Merkel cell carcinoma of the earlobe in a young healthy man.
AB  - Merkel cell carcinoma (MCC) is an uncommon neuroendocrine cutaneous tumor with
      poor prognosis. It has the high rate of recurrence, mortality, regional nodal
      involvement, and distant metastases. It is difficult to diagnose MCC because of
      its non-specific clinical findings. It usually occurs on sun-exposed areas of the
      skin, mostly at head and neck. There is a difference in the incidence and
      prognosis according to site in the head and neck. However, there is no consented
      site-specific diagnosis, treatment or follow-up protocol for MCC at the head and
      neck. We herein report a case of MCC arising in the right earlobe of an otherwise
      healthy young man who has been diagnosed early, thereby successfully treated.
      With our closed follow-up, there was no tumor recurrence or complication at 33
      months after diagnosis.

PMID- 30282433
TI  - Skeletal cavernous hemangiomas of the frontal bone with orbital roof and rim
      involvement.
AB  - Skeletal cavernous hemangiomas are rare, benign tumors that may involve the
      supraorbital rim and orbital roof. However, such involvement is extremely rare.
      We report a case of skeletal cavernous hemangioma of the frontal bone involving
      the orbital roof and rim. En bloc excision and reconstruction, using a calvarial
      bone graft for the orbital roof and rim defect, was performed. It is important
      not only to perform total excision of skeletal cavernous hemangiomas, but to
      properly reconstruct the defects after the total excision since several
      complications can arise from an orbital roof and rim defect.

PMID- 30282434
TI  - Treatment of post-traumatic hematoma and fibrosis using hyaluronidase injection.
AB  - Patients complaining of swelling and hematoma caused by contusion of the face can
      be easily seen in the emergency room. Most of the treatments were conservative
      treatments such as ice bag application, mild compression dressing, and massage.
      During the follow-up, fibrosis progression due to hematoma was frequently
      observed in the contusion site. When hematoma or fibrosis is confirmed,
      hyaluronidase (H-lase) 1,500 IU and 2 mL of normal saline were mixed and
      subcutaneously injected in crisscross manner. To evaluate the improvement of
      hematoma before and after hyaluronidase injection, three plastic surgeons
      evaluated using the Vancouver scar scale and compared preoperative and
      postoperative images. Hematoma and fibrosis after facial trauma improved after
      hyaluronidase injection for early treatment.

PMID- 30282435
TI  - Staged lower lip reconstruction following gangrenous stomatitis in an
      immunosuppressed patient.
AB  - A 70-year-old male with a history of diabetes mellitus, hypertension, and
      coronary stent insertion visited our hospital 7 days after biting his lower lip.
      Swelling and inflammation had worsened despite debridement and antibiotic
      treatment. On the 8th hospital day, fungal infection with Candida albicans and
      superimposed bacterial infection with Klebsiella pneumoniae were found on tissue
      culture. Extensive necrosis resulted in a defect of approximately 3/4 of the
      entire lower lip and a full-layer skin defect from the vermilion to the
      gingivobuccal sulcus at the right corner of the mouth. To correct drooling,
      incomplete lip sealing, and trismus, staged reconstruction was performed with
      consideration of cosmetic and functional features. The treatment process using
      staged reconstruction and antifungal treatment for an extensive lower lip defect
      caused by fungal stomatitis is described.

PMID- 30282436
TI  - A rare case of isolated schwannoma in infraorbital nerve.
AB  - A schwannoma is a benign tumor that develops from Schwann cells. It is known to
      occur more frequently in women than men, and about one third of schwannoma cases
      occur in the head and neck area. It is also known to originate mainly in the
      auditory nerve. However, it is rarely associated with the trigeminal nerve, and
      especially, schwannomas related to the infraorbital nerve are very rare. we
      report a rare case of a schwannoma involving the infraorbital branch of the
      trigeminal nerve in a 45-year old male adult. The patient underwent physical
      examination and magnetic resonance imaging. The mass was approached through
      subciliary approach that is familiar to the plastic surgeon and completely
      resected. Histopathological findings showed pointed to a benign schwannoma.
      Infraorbital nerve schwannoma is difficult to distinguish from other diseases by
      means of clinical symptoms, physical findings, or imaging. In spite of its
      rarity, infraorbital nerve schwannoma may be considered a possible diagnosis in
      the case of mass on cheek. Assessment by computed tomography or magnetic
      resonance imaging is necessary for proper diagnosis. About the surgical approach,
      excision through the subciliary approach should be considered rather than the
      direct transfacial approach in view of stability, cosmetic effects, and
      familiarity.

PMID- 30282437
TI  - New economical and simple device for intraoperative expansion on small and medium
      sized soft tissue defects.
AB  - Intraoperative expansion has been used to cover small to large defects without
      disadvantages of the conventional tissue expanders. Various materials, for
      example, expanders and Foley catheters are being used. We introduce a new,
      convenient and economical device immediately available in the operating room,
      according to the defect size for intraoperative expansion, with latex gloves or
      balloons. The retrospective study was done with 20 patients who presented with
      skin and soft tissue defects. During the operation, expansion was done with latex
      gloves or balloons inflated with saline through an intravenous line and a three
      way stopcock. After the inflation, the glove was removed and skin was covered
      with expanded tissue. A careful decision was made regarding the inflation volume
      and placement of the expander according to the defect size. There were no
      postoperative complications. The skin contracture and tension was minimal with a
      texture similar to the adjacent tissue. The new intraoperative expansion devices
      with latex gloves and balloons were cheap and made easily right in the operation
      room. The reconstruction of small to large sized skin defects can be done
      successfully, functionally and aesthetically without using expensive commercial
      materials.

PMID- 30282438
TI  - Histopathology of the synovial tissue: perspectives for biomarker development in
      chronic inflammatory arthritides.
AB  - The histopathological and molecular analysis of the synovial tissue has
      contributed to fundamental advances in our comprehension of arthritis
      pathogenesis and of the mechanisms of action of currently available treatments.
      On the other hand, its exploitation in clinical practice for diagnostic or
      prognostic purposes as well as for the prediction of treatment response to
      specific disease-modifying anti-rheumatic drugs is still limited. In this review,
      we present an overview of recent advances in the field of synovial tissue
      research with specific reference to the methods for synovial tissue collection,
      approaches to synovial tissue analysis and current perspectives for the
      exploitation of synovial tissue-derived biomarkers in chronic inflammatory
      arthritides.

PMID- 30282439
TI  - Histopathology of the muscle in rheumatic diseases.
AB  - The presence of muscular symptoms is common in rheumatological clinical practice,
      but often the differential diagnosis between muscular involvement in connective
      tissue diseases, vasculitis and drug-induced myopathy may be difficult. In
      addition to clinical assessment, laboratory analysis and instrumental
      examinations, muscle biopsy may help to clarify the diagnosis in patients with
      muscular involvement. The purpose of this review is to provide a critical
      analysis of the current medical literature on muscular histopathology, to help
      clinicians to identify when to perform muscular biopsy and to provide a practical
      guide to a better understanding of the pathology report. Moreover, we provide an
      overview of the muscular involvement and the most common histopathological
      findings in rheumatic diseases.

PMID- 30282440
TI  - Histopathology of salivary glands.
AB  - Salivary gland (SG) biopsy is a technique broadly applied for the diagnosis of
      primary Sjogren's syndrome (pSS), lymphoma accompanying SS, sarcoidosis,
      amyloidosis, and IgG4-related disease The most peculiar feature of pSS on biopsy
      is focal lymphocytic sialadenitis. In the past, several histological scores have
      been reported in the literature to describe glandular involvement during pSS.
      However, the variability among centres in reporting glandular scores is one of
      the rationales behind the development of standardised consensus guidance. SGs as
      well as lacrimal glands are involved in up to 50% of patients with IgG4-related
      disease with 3 histopathological hallmarks such as dense lymphoplasmacytic
      infiltration, storiform fibrosis and obliterative phlebitis. SGs can be also
      affected by amyloidosis with MSG biopsy being more sensitive than that of rectal
      mucosa or subcutaneous fat. SG involvement is a rare manifestation during
      sarcoidosis, and the presence of non-caseating granulomas needs to be
      differentiated from granulomas of other etiology. This review article provides an
      overview of normal and pathological SGs in the context of rheumatic diseases,
      identifying key elements in the tissue as diagnostic and prognostic biomarkers,
      useful in the current clinical practice.

PMID- 30282441
TI  - Histopathology of vasculitis.
AB  - The range of pathologies that are related to primitive vasculitis is broad,
      complex and not as typical as we would expect. Clinicians should be aware that
      several forms of primitive and systemic vasculitis, regardless of the size of the
      affected vessel, may exhibit identical histological alterations. This observation
      has important clinical implications as it means that cases of vasculitis do not
      correspond clinically and histologically. Thus, while histology remains the
      diagnostic gold standard, it can be used only as part of the most complete
      clinical assessment possible. Another point worth of the clinician's attention is
      that vasculitis histology changes over time, as do disease evolution and
      activity, even without considering the masking effects of treatment and the
      possibility of sampling error due to the patchy occurrence of vasculitis. The
      purpose of this review is to identify the most common forms of vasculitis in
      clinical practice, and to provide guidance to the clinician on the pathology of
      the vessels.

PMID- 30282442
TI  - Diagnostic and prognostic role of renal histopathology in rheumatic diseases.
AB  - The objective was to evaluate renal involvement in several rheumatic diseases
      (i.e. rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome,
      systemic sclerosis, systemic vasculitides). The method chosen was to define
      histopathological profiles reported in renal biopsies performed on patients with
      renal involvement due to different rheumatic diseases. Renal involvement observed
      in patients with rheumatic disease can be the direct result of the disease per se
      and/or a complication of drugs used in the disease treatment. The clinical
      pathological correlations derived from the study of renal tissues can be useful
      for differential diagnosis, prognosis assessment and therapeutic decisions. Renal
      biopsy should be considered as an important tool for the management of
      nephropathies in patients with systemic rheumatic diseases.

PMID- 30282443
TI  - Histopathology of the gut in rheumatic diseases.
AB  - The gastrointestinal tract regulates the trafficking of macromolecules between
      the environment and the host through an epithelial barrier mechanism and is an
      important part of the immune system controlling the equilibrium between tolerance
      and immunity to non-self-antigens. Various evidence indicates that intestinal
      inflammation occurs in patients with rheumatic diseases. In many rheumatic
      diseases intestinal inflammation appears to be linked to dysbiosis and possibly
      represents the common denominator in the pathogenesis of different rheumatic
      diseases. The continuative interaction between dysbiosis and the intestinal
      immune system may lead to the aberrant activation of immune cells that can re
      circulate from the gut to the sites of extraintestinal inflammation as observed
      in patients with ankylosing spondylitis. The exact contribution of genetic
      factors in the development of intestinal inflammation in rheumatic diseases needs
      to be clarified.

PMID- 30282444
TI  - Histopathology of the skin in rheumatic diseases.
AB  - Rheumatological systemic autoimmune diseases, such as connective tissue diseases,
      rheumatoid arthritis or spondyloarthritis, are characterized by the presence of
      joint involvement associated with extra-articular manifestations. Among them,
      cutaneous diseases are often the most relevant and representative clinical
      manifestation, as in psoriatic arthritis, scleroderma or systemic lupus
      erythematosus. In this context, it is useful for rheumatologists to understand
      better skin diseases and their histopathological features. Evaluation of skin
      biopsy specimens can be helpful not only to confirm the diagnosis in both classic
      and clinically atypical variants, but also to improve further our knowledge of
      the pathogenetic mechanisms and the close link between skin and articular
      diseases. In this review, we discuss the clinical features, diagnostic evaluation
      and the histopathological features of skin manifestation of the most relevant
      rheumatological autoimmune diseases.

PMID- 30282445
TI  - The Health Burden of Cancer Attributable to Obesity in Korea: A Population-Based
      Cohort Study.
AB  - Purpose: Considering the health impact of obesity and cancer, it is important to
      estimate the burden of cancer attributable to high body mass index (BMI).
      Therefore, the present study attempts to measure the health burden of cancer
      attributable to excess BMI, according to cancer sites. Materials and Methods: The
      present study used nationwide medical check-up sample cohort data (2002-2015).
      The study subjects were 496,390 individuals (268,944 men and 227,446 women). We
      first calculated hazard ratio (HR) in order to evaluate the effect of excess BMI
      on cancer incidence and mortality. Then, the adjusted HR values and the
      prevalence of excess BMI were used to calculate the population attributable risk.
      This study also used the Global Burden of Disease method, to examine the health
      burden of obesity-related cancers attributable to obesity. Results: The highest
      disability-adjusted life year (DALY) values attributable to overweight and
      obesity in men were shown in liver cancer, colorectal cancer, and gallbladder
      cancer. Among women, colorectal, ovarian, and breast (postmenopausal) cancers had
      the highest DALYs values attributable to overweight and obesity. Approximately
      8.0% and 12.5% of cancer health burden (as measured by DALY values) among obesity
      related cancers in men and women, respectively, can be prevented. Conclusions:
      Obesity has added to the health burden of cancer. By measuring the proportion of
      cancer burden attributable to excess BMI, the current findings provide support
      for the importance of properly allocating healthcare resources and for developing
      cancer prevention strategies to reduce the future burden of cancer.

PMID- 30282446
TI  - Clinical Benefit of Maintenance Therapy for Advanced Biliary Tract Cancer
      Patients Showing No Progression after First-Line Gemcitabine Plus Cisplatin.
AB  - Purpose: Gemcitabine plus cisplatin (GemCis) is the standard first line
      chemotherapy for patients with advanced biliary tract cancer (BTC). In ABC-02
      study, the BTC patients received up to 6-8 cycles of three-weekly GemCis;
      however, those without progression often receive more than 6-8 cycles. The
      clinical benefit of maintenance treatment in patients without progression is
      uncertain. Materials and Methods: Advanced BTC patients treated with GemCis
      between April 2010 and February 2015 at Asan Medical Center, Seoul, Korea, were
      retrospectively analysed. The patients without progression after 6-8 cycles were
      stratified according to further treatment i.e. with or without further cycles of
      GemCis (maintenance vs observation groups). The primary endpoint was overall
      survival (OS) and progression-free survival (PFS). Results: Among the 740 BTC
      patients in the initial screen, 231 cases (31.2%) were eligible for analysis (111
      in the observation group, 120 in the maintenance group). The median OS from the
      GemCis initiation was 20.5 months (95% confidence interval [CI], 15.4 to 25.6)
      and 22.4 months (95% CI, 17.0 to 27.8) in the observation and maintenance groups,
      respectively (p=0.162). The median PFS was 10.4 months (95% CI, 7.0 to 13.8) and
      13.2 months (95% CI, 11.3 to 15.2), respectively (p=0.320). Conclusions: GemCis
      maintenance is not associated with an improved survival outcome.

PMID- 30282447
TI  - Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed
      Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter,
      Open-Label Phase 3 Trial.
AB  - Purpose: Rituximab with cyclophosphamide, doxorubicin, vincristine, and
      prednisone administered every 3 weeks (R-CHOP-21) is the standard care for
      diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R
      CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population.
      Materials and Methods: Newly diagnosed DLBCL patients were centrally, randomly
      assigned (1:1) to receive R-CHOP-14 or R-CHOP-21. R-CHOP-14 was administered
      every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point
      was disease-free survival (DFS). Secondary end points included overall survival
      (OS), progression-free survival (PFS), response rate and toxicities. Results:
      Seven hundred and two patients were randomly assigned to receive R-CHOP-14
      (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two
      groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2%
      for R-CHOP-21, p=0.311) , 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21,
      p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447).
      Patients with an International Prognostic Index (IPI) score >= 2 had a poorer
      prognosis compared to those with an IPI score <2. Grade 3/4 hematologic and non
      hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP
      21. Conclusion: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP
      21 in Asian population. With manageable and similar toxicities, both of the two
      regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI
      >=2, new combination regimens based on R-CHOP deserve further investigation to
      improve efficacy.

PMID- 30282448
TI  - Retrospective Study of the Significant Predictive Role of Inflammatory Degree in
      Initial and Repeat Prostate Biopsy Specimens for Detecting Prostate Cancer.
AB  - Purpose: The purpose of this study was to determine whether histologic
      inflammation (HI) in initial and repeat prostate biopsy specimens was
      significantly associated with the detection of prostate cancer. Materials and
      Methods: Between 2005 and 2017, the clinicopathological records of patients with
      high prostate-specific antigen (PSA) levels who underwent initial and repeat
      prostate biopsies were retrospectively reviewed. The presence of HI and its
      degree in each biopsied specimen were interpreted by one uropathologist with 20
      years of experience. The association between HI and cancer diagnosis was
      statistically assessed, with p<0.05 considered significant, and the cancer and
      non-cancer groups were compared. Results: Among the 522 patients with a median
      PSA levels of 6.5 ng/dL, including 258 (49.4%) whose cancer was diagnosed
      following repeat biopsy, the median degrees of HI in the initial and repeat
      biopsies were 25.0% and 41.7%, respectively. Furthermore, 211 (40.4%) and 247
      (47.3%) patients had HI (>0%) on biopsied specimens, respectively. Comparison of
      the cancer and noncancer groups revealed that a greater rate of HI specimens in
      the initial biopsy was associated with fewer prostate cancer diagnoses following
      repeat biopsy (p<0.001). Other comparisons between the cancer and non-cancer
      groups showed that the cancer group had a significantly higher rate of
      hypertension, whereas those non-cancer group had a significantly higher rate of
      benign prostatic hyperplasia and prostatitis (p<0.05). Conclusion: A finding of a
      lesser degree of HI in the initial and a greater degree of HI in the repeat
      biopsied specimens was associated with the higher probability of cancer diagnosis
      in patients with high PSA levels.

PMID- 30282449
TI  - Jab1 Silencing Inhibits Proliferation and Sensitizes to Cisplatin in Biliary
      Tract Cancer.
AB  - Purpose: Jab1 is a coactivator of c-Jun that enhances the transcriptional
      function of c-Jun. Jab1 is frequently overexpressed in various cancers and is
      associated with poor prognosis of cancer patients. Thus, Jab1 could be a
      potential therapeutic target in cancer. However, the role of Jab1 in biliary
      tract cancer (BTC) has not been studied. Materials and Methods: We performed in
      vitro and in vivo experiments to evaluate the therapeutic potential of Jab1
      inhibition in BTC. Results: Among 8 BTC cell lines, many showed higher Jab1
      expression levels. In addition, Jab1 silencing by siRNA increased p27 expression
      levels. SNU478 and HuCCT-1 cells exhibited profound Jab1 knockdown and increased
      p27 expression by Jab1-specific siRNA transfection. Jab1 silencing induced anti
      proliferative and anti-migratory effects and resulted in G1 cell cycle arrest in
      SNU478 and HuCCT-1 cells. In addition, Jab1 silencing potentiated the anti
      proliferative and anti-migratory effects of cisplatin by increasing DNA damage.
      Interestingly, Jab1 knockdown increased PTEN protein half-life, resulting in
      increased PTEN expression. In the HuCCT-1 mouse xenograft model, stable knockdown
      of Jab1 by shRNA also showed anti-proliferative effects in vivo, with decreased
      Ki-67 expression and AKT phosphorylation and increased Terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling and p27 expression. Conclusion: Jab1
      knockdown demonstrated anti-proliferative and anti-migratory effects in BTC cells
      by increasing DNA damage and stabilizing PTEN, resulting in G1 cell cycle arrest.
      In addition, Jab1 silencing potentiated the anti-proliferative effects of
      cisplatin. Our data suggest that Jab1 may be a potential therapeutic target in
      BTC that is worthy of further investigations.

PMID- 30282450
TI  - Comparison of the 7th and the 8th AJCC Staging System for Non-metastatic D2
      Resected Lymph Node-Positive Gastric Cancer Treated with Different Adjuvant
      Protocols.
AB  - Purpose: The purpose of this study was to compare prognostic differentiation
      performances of the 7th and the 8th edition of American Joint Commission on
      Cancer (AJCC) staging system for gastric cancer (GC) patients. Materials and
      Methods: A total of 1,633 GC patients who underwent curative D2 resection
      followed by adjuvant chemotherapy alone (CA) or concurrent chemo-radiotherapy
      (CCRT) from 2004 to 2013 were included. Concordance index (c-index) was applied
      to compare the discriminatory ability. Results: In the 8th edition, migration of
      stage was detected in 248 (15.2%) patients. Among them, 121 patients were up
      staged while 127 patients were down-staged. Overall, there was no statistically
      significant difference in the discriminatory ability between the 7th and 8th
      editions. The new edition of staging system, however, showed a trend of better
      prognostic performance not only in recurrence-free survival (c-index = 0.734; 95%
      confidence interval [CI], 0.706 to 0.762 in the 7th edition vs. c-index = 0.740;
      95% CI, 0.712 to 0.768 in the 8th edition; p=0.14), but also in overall survival
      (c-index = 0.717; 95% CI, 0.688 to 0.745 in the 7th edition vs. c-index = 0.722;
      95% CI, 0.694 to 0.751 in the 8th edition; p=0.19), especially in stage III. This
      finding was repeated in the subgroup analysis regardless of adjuvant CA or CCRT.
      Conclusion: Generally, the 8th edition of AJCC staging system had failed to show
      a superior discriminatory ability for curatively D2 resected GC patients than the
      7th edition, although there was a trend of better prognostic performance of the
      new edition, regardless of adjuvant treatment method.

PMID- 30282451
TI  - A Phage Display-Identified Peptide Selectively Binds to Kidney Injury Molecule-1
      (KIM-1) and Detects KIM-1-Overexpressing Tumors in vivo.
AB  - Purpose: This study was carried out to identify a peptide that selectively binds
      to kidney injury molecule-1 (KIM-1) by screening a phage-displayed peptide
      library and to use the peptide for the detection of KIM-1overexpressing tumors in
      vivo. Materials and Methods: Biopanning of a phage-displayed peptide library was
      performed on KIM-1-coated plates. The binding of phage clones, peptides, and a
      peptide multimer to the KIM-1 protein and KIM-1-overexpressing and KIM-1-low
      expressing cells was examined by enzyme-linked immunosorbent assay, fluorometry,
      and flow cytometry. A biotin-peptide multimer was generated using NeutrAvidin. In
      vivo homing of the peptide to KIM-1-overexpressing and KIM-1-low expressing
      tumors in mice was examined by whole-body fluorescence imaging. Results: A phage
      clone displaying the CNWMINKEC peptide showed higher binding affinity to KIM-1
      and KIM-1-overexpressing 769-P renal tumor cells compared to other phage clones
      selected after biopanning. The CNWMINKEC peptide and a NeutrAvidin/biotin
      CNWMINKEC multimer selectively bound to KIM-1 over albumin and to KIM-1
      overexpressing 769-P cells and A549 lung tumor cells compared to KIM-1-low
      expressing HEK293 normal cells. Co-localization and competition assays using an
      anti-KIM-1 antibody demonstrated that the binding of the CNWMINKEC peptide to 769
      P cells was specifically mediated by KIM-1. The CNWMINKEC peptide was not
      cytotoxic to cells and was stable for up to 24 hours in the presence of serum.
      Whole-body fluorescence imaging demonstrated selective homing of the CNWMINKEC
      peptide to KIM-1-overexpressing A498 renal tumor compared to KIM-1-low expressing
      HepG2 liver tumor in mice. Conclusion: The CNWMINKEC peptide is a promising probe
      for in vivo imaging and detection of KIM-1-overexpressing tumors.

PMID- 30282452
TI  - Immunohistochemistry Biomarkers Predict Survival in Stage II/III Gastric Cancer
      Patients: From a Prospective Clinical Trial.
AB  - Purpose: Identification of biomarkers to predict recurrence risk is essential to
      improve adjuvant treatment strategies in stage II/III gastric cancer patients.
      This study evaluated biomarkers for predicting survival after surgical resection.
      Materials and Methods: This post-hoc analysis evaluated patients from the CLASSIC
      trial who underwent D2 gastrectomy with or without adjuvant chemotherapy
      (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of
      thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1),
      and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC)
      staining to determine their predictive values. Results: Among 139 patients, IHC
      analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%),
      and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS
      expression tended to predict poor disease-free survival (DFS; hazard ratio [HR],
      1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR,
      0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox
      analysis. In the subgroup analysis, poor DFS was independently predicted by high
      TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66).
      High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and
      OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic
      impact of high ERCC1 expression was not significant in the multivariate Cox
      analysis. Conclusion: This study shows that high TS expression is a predictive
      factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy,
      whereas PD-L1 expression is a favorable prognostic factor in locally advanced
      gastric cancer patients.

PMID- 30282453
TI  - Metal-Free Single Atom Catalyst for N2 Fixation Driven by Visible Light.
AB  - Solar nitrogen (N2) fixation is the most attractive way for the sustainable
      production of ammonia (NH3), but the development of a highly active, long-term
      stable and low-cost catalyst remains a great challenge. Current research efforts
      for N2 reduction mainly focus on the metal-based catalysts using the
      electrochemical approach, while metal-free or solar-driven catalysts have been
      rarely explored. Herein, on the basis of a concept of electron "acceptance
      donation", a metal-free photocatalyst, namely, boron (B) atom, decorated on the
      optically active graphitic-carbon nitride (B/g-C3N4), for the reduction of N2 is
      proposed by using extensive first-principles calculations. Our results reveal
      that gas phase N2 can be efficiently reduced into NH3 on B/g-C3N4 through the
      enzymatic mechanism with a record low onset potential (0.20 V). Moreover, the B
      decorated g-C3N4 can significantly enhance the visible light absorption,
      rendering them ideal for solar-driven reduction of N2. Importantly, the as
      designed catalyst is further demonstrated to hold great promise for synthesis due
      to its extremely high stability. Our work is the first report of metal-free
      single atom photocatalyst for N2 reduction, offering cost-effective opportunities
      for advancing sustainable NH3 production.

PMID- 30282454
TI  - Cyclohexenynone Precursors: Preparation via Oxidative Dearomatization Strategy
      and Reactivity.
AB  - A unique approach toward the preparation of cyclohexenynone equivalents was
      successfully developed via oxidative dearomatization of aryne precursors,
      featuring multiple functionalities on the target rings. Upon activation, these in
      situ formed cyclohexenynone intermediates exhibit good to excellent reactivity
      with various trapping agents. Moreover, an unprecedented cascade was discovered
      with aryl allyl sulfoxides, revealing a deeper utilization of the alkyne bond by
      concomitantly introducing one nucleophile and two electrophiles.

PMID- 30282456
TI  - Ice Clouds: Atmospheric Ice Nucleation Concept versus the Physical Chemistry of
      Freezing Atmospheric Drops.

PMID- 30282457
TI  - Top Selected Papers in the Physical Chemistry of Energy Materials 2016-2017.

PMID- 30282455
TI  - Sacrificial Cobalt-Carbon Bond Homolysis in Coenzyme B12 as a Cofactor
      Conservation Strategy.
AB  - A sophisticated intracellular trafficking pathway in humans is used to tailor
      vitamin B12 into its active cofactor forms, and to deliver it to two known B12
      dependent enzymes. Herein, we report an unexpected strategy for cellular
      retention of B12, an essential and reactive cofactor. If methylmalonyl-CoA mutase
      is unavailable to accept the coenzyme B12 product of adenosyltransferase, the
      latter catalyzes homolytic scission of the cobalt-carbon bond in an
      unconventional reversal of the nucleophilic displacement reaction that was used
      to make it. The resulting homolysis product binds more tightly to
      adenosyltransferase than does coenzyme B12, facilitating cofactor retention. We
      have trapped, and characterized spectroscopically, an intermediate in which the
      cobalt-carbon bond is weakened prior to being broken. The physiological relevance
      of this sacrificial catalytic activity for cofactor retention is supported by the
      significantly lower coenzyme B12 concentration in patients with dysfunctional
      methylmalonyl-CoA mutase but normal adenosyltransferase activity.

PMID- 30282458
TI  - Spotlights: Volume 9, Issue 19.

PMID- 30282460
TI  - Epidemiology of Upper Extremity Injuries in NCAA Men's and Women's Ice Hockey:
      Addendum.

PMID- 30282461
TI  - Change in Food and Beverage Availability and Marketing Following the Introduction
      of a Healthy Food Financing Initiative-Supported Supermarket.
AB  - PURPOSE: The Healthy Food Financing Initiative (HFFI) aims to expand access to
      healthy foods in low-resourced communities across the United States. This study
      examined changes in food and beverage availability and marketing in nearby small
      food stores after the opening of an HFFI-supported supermarket in a predominately
      low-income and African American community. DESIGN: Natural experiment. SETTING:
      Rockford, Illinois. PARTICIPANTS: A full audit was conducted of the small grocery
      and limited service stores located in a 1-mile radius around the new supermarket
      (N = 22) and a 1-square mile area within a nearby demographically matched
      comparison community (N = 18). Stores were audited in 2015 (1 month preopening)
      and 2016 (1 year afterward). MEASURES: Store characteristics, item availability,
      and interior and exterior promotions/advertisements were examined. ANALYSIS:
      Difference-in-difference (DID) regression models assessed pre- and
      postintervention changes in availability and marketing between small food stores
      in the intervention and comparison communities. RESULTS: The DID regression
      models indicated no difference between intervention and comparison communities
      with respect to changes in availability and marketing of all food items with the
      exception of frozen vegetables which had higher availability postintervention in
      the comparison community versus intervention (beta for interaction term = .67;
      standard error: 0.33; P = .04). CONCLUSION: After the opening of the HFFI
      supported supermarket, food and beverage availability and marketing in nearby
      small food stores did not change significantly. However, the wide range of staple
      foods offered by the supermarket contributed to the expansion of healthy food
      retail in the intervention community.

PMID- 30282462
TI  - Asymptomatic dislocation of a Watchman left atrial appendage occluder.
AB  - Device dislocation associated with left atrial appendage closure with a Watchman
      device is rare. Few cases of surgical treatment have been reported. Therefore,
      surgical options and the effects of the surgery on subsequent operations are
      unknown. This device was implanted in 2 patients in another hospital because of
      frequent brain and intestinal bleeding related to coagulation therapy for atrial
      fibrillation. However, routine echocardiography revealed dislocation from the
      left atrial appendage orifice in the early and late postoperative periods.
      Emergency surgical removal of the devices was performed. Perioperative device
      management and treatment strategies are discussed briefly.

PMID- 30282463
TI  - What are the determinants of a concerned vision of the future when living with
      type 2 diabetes? Results from the E3N-AfterDiab study.
AB  - Objectives Identification of characteristics associated with a negative
      experience with type 2 diabetes may help to develop novel intervention to improve
      the outlook of people with the disease. Our aim was to identify determinants of a
      self-reported concerned vision about the future when living with type 2 diabetes.
      Methods In 2630 women with type 2 diabetes from the E3N-AfterDiab study, we used
      multivariable logistic regression models to derive odds-ratios and 95% confidence
      intervals. Results Women with elevated HbA1c levels (OR = 2.42 (1.67-3.49) for
      >=7.2% when compared to <6.2%), or treated with injected glucose lowering
      treatments (OR = 1.37 [1.05-1.81]) had a higher risk of a concerned vision of the
      future. Age and obesity were associated with a decreased risk. Hypertension,
      duration of diabetes, smoking, fasting glucose levels, and years of education
      were not associated with a concerned vision of the future. Discussion Our
      findings highlight the importance of both glycemic control and the type of
      treatment on the perception of the future when living with type 2 diabetes.
      Subgroups of patients based on these characteristics may receive a specific
      attention from healthcare professionals to address potential concerns related
      with diabetes management or the fear of complications.

PMID- 30282464
TI  - Establishment of glycated albumin unit conversion equation from the standardized
      value (mmol/mol) to the routinely used value (%).
AB  - BACKGROUND: To promote glycated albumin standardization, the Committee on
      Diabetes Mellitus Indices, Japan Society of Clinical Chemistry published the
      recommended reference method and is supplying the reference standard material
      (JCCRM 611). In this study, we evaluated the basic performance of 'standardized
      enzymatic method' that is traceable to JCCRM 611 and established a unit
      conversion formula from standardized glycated albumin value (mmol/mol) to the
      routinely used glycated albumin value (%). METHODS: To evaluate the accuracy and
      within-run reproducibility of the 'standardized enzymatic method', JCCRM 611 was
      measured 20 times. To establish the unit conversion formula, serum specimens with
      known HbA1c concentrations were collected, and their glycated albumin (%) and
      glycated albumin (mmol/mol) were measured. RESULTS: The accuracy of glycated
      albumin value of the 'standardized enzymatic method' was 100.8-103.0%. The within
      run reproducibility CV (coefficient of variation, %) of glycated albumin value
      was 0.6-0.9%. In total, 240 serum specimens were collected, and the distribution
      of their HbA1c values was HbA1c <= 4.9% ( n = 23), 5.0-5.9% ( n = 50), 6.0-6.9%,
      ( n = 44), 7.0-7.9% ( n = 40), 8.0-8.9% ( n = 37) and >=9.0% ( n = 46). The unit
      conversion equation was defined as: GA (%) = 0.05652 * GA (mmol/mol)-0.4217 ( r =
      0.999). Glycated albumin (%) calculated by the equation was in close agreement
      (96.6-104.2%) with the actual measured glycated albumin (%). CONCLUSIONS: The
      glycated albumin unit conversion formula was established from mmol/mol to %. This
      formula provides an easy method to convert the unit and is expected to be useful
      for the standardization of glycated albumin measurement.

PMID- 30282465
TI  - Clinical Outcomes Following Minimally Invasive Dorsal Cheilectomy for Hallux
      Rigidus.
AB  - BACKGROUND: Following failure of conservative treatment, a dorsal cheilectomy can
      be performed for patients in early stages of hallux rigidus by a traditional open
      approach or by a minimally invasive technique. We report our clinical outcomes
      following minimally invasive dorsal cheilectomy (MIDC). METHODS: Eighty-nine
      patients (98 feet) with symptomatic hallux rigidus treated between 2011 and 2016
      were included in this study. The average age was 54 years. Manchester-Oxford Foot
      Questionnaire (MOxFQ) scores and visual analog scale (VAS) pain scores were
      collected. The mean follow-up was 50 months. RESULTS: The average VAS score
      improved from 8.0 preoperatively to 3 postoperatively. The mean MOxFQ summary
      index score decreased from 58.6 preoperatively to 30.5 postoperatively. All 3
      MOxFQ domains also improved. Swelling took an average of 5.3 weeks to settle.
      There were 2 wound infections and 2 delayed wound healings. Two patients had
      transient nerve paraesthesia, while 2 patients had permanent numbness in the
      dorsomedial cutaneous nerve distribution. Twelve patients (12%) underwent
      reoperation, of which 7 had a first metatarsophalangeal joint arthrodesis for
      ongoing pain, 4 had repeat cheilectomy for residual impingement, and 1 had an
      open removal of loose bone. CONCLUSION: Our results suggest that MIDC resulted in
      improvement in patient-reported outcome measures and was a safe technique with
      minimal complications. The complications were similar to open cheilectomy. There
      was an associated learning curve as 5 of our reoperations were due to incomplete
      cheilectomy. Coughlin grade 1 did well with MIDC as with open cheilectomy as none
      went onto an arthrodesis. However, 10% (7/65) of our grade 2 and 3 cases went on
      to an arthrodesis. LEVEL OF EVIDENCE: Level IV, retrospective case series.

PMID- 30282466
TI  - Paclitaxel-loaded TPGS enriched self-emulsifying carrier causes apoptosis by
      modulating survivin expression and inhibits tumour growth in syngeneic mammary
      tumours.
AB  - Paclitaxel (PTX) in its commercial products exhibits adverse effects owing to
      excipients and also has poor oral bioavailability. Present work is directed
      towards development of tocopheryl polyethylene glycol succinate-assisted self
      nanoemulsifying system (SEDDS) for oral delivery of PTX. Box-Behnken design of
      experiment was employed to optimize PTX-SEDDS and was characterized for droplet
      size (29.76 +/- 2.64 nm), zeta potential (-21.46 +/- 2.52 mV), PDI (0.177 +/-
      0.012), drug content (4.97 +/- 0.98 mg), entrapment efficiency (98.33 +/- 0.54%)
      and in vitro drug release (51.03 +/- 2.23% PTX at 72 h). PTX-SEDDS exhibited
      IC50; 1.58 +/- 0.12 uM and a 52.46-folds higher cell uptake in MDA-MB-231 cells
      along with cellular and nuclear morphology changes. Significantly higher G2M cell
      cycle arrest, apoptosis, mitochondrial membrane potential disruption and ROS
      production was exhibited by PTX-SEDDS in comparison to Taxol. Up-regulation of
      Bax, p21, cleaved-caspase 3, -caspase 9 and down-regulation of Bcl2 and survivin
      suggested apoptosis via intrinsic pathways. Pharmacokinetic study showed
      approximately 4-folds higher oral bioavailability of PTX-SEDDS than Taxol.
      Significant reduction in tumour volume and weight was observed in syngeneic
      mammary tumour in SD rats. Tumour histopathology and TUNEL assay showed apoptosis
      in tumour tissue. PTX-SEDDS caused low lung metastasis, and was safe and stable.
      Conclusively, PTX-SEDDS could be suitable option for oral delivery of PTX.

PMID- 30282467
TI  - Hydrogen atom transfer in the radical cations of tryptophan-containing peptides
      AW and WA studied by mass spectrometry, infrared multiple-photon dissociation
      spectroscopy, and theoretical calculations.
AB  - Two types of radical cations of tryptophan-the pi-radical cation and the
      protonated tryptophan-N radical-have been studied in dipeptides AW and WA. The pi
      radical cation produced by removal of an electron during collision-induced
      dissociation of a ternary Cu(II) complex was only observed for the AW peptide. In
      the case of WA, only the ion corresponding to the loss of ammonia, [WA-NH3] *+,
      was observed from the copper complex. Both protonated tryptophan-N radicals were
      produced by N-nitrosylation of the neutral peptides followed by transfer to the
      gas phase via electrospray ionization and subsequent collision-induced
      dissociation. The regiospecifically formed N* species were characterized by
      infrared multiple-photon dissociation spectroscopy which revealed that the WA
      tryptophan-N* radical remains the nitrogen radical, while the AW nitrogen radical
      rearranges into the pi-radical cation. These findings are supported by the
      density functional theory calculations that suggest a relatively high barrier for
      the radical rearrangement (N* to pi) in WA (156.3 kJ mol-1) and a very low
      barrier in AW (6.1 kJ mol-1). The facile hydrogen atom migration in the AW system
      is also supported by the collision-induced dissociation of the tryptophan-N
      radical species that produces fragments characteristic of the tryptophan pi
      radical cation. Gas-phase ion-molecule reactions with n-propyl thiol have also
      been used to differentiate between the pi-radical cations (react by hydrogen
      abstraction) and the tryptophan-N* species (unreactive) of AW.

PMID- 30282468
TI  - Race-Specific Patterns of Treatment Intensification Among Hypertensive Patients
      Using Home Blood Pressure Monitoring: Analysis Using Defined Daily Doses in the
      Heart Healthy Lenoir Study.
AB  - BACKGROUND: Racial disparities in blood pressure (BP) control persist, but
      whether differences by race in antihypertensive medication intensification (AMI)
      contribute is unknown. OBJECTIVE: To compare AMI by race for patients with
      elevated home BP readings. METHODS: This prospective cohort study followed adult
      patients from 6 rural primary care practices who used home BP monitoring (HBPM)
      and recorded/reported values. For providers, AMI was encouraged when mean HBPM
      systolic blood pressure (SBP) values were ?135 mm Hg; patients received phone
      based coaching on HBPM technique and sharing HBPM findings. AMI was assessed
      between baseline and 12 months using defined daily dose (DDD) and summed to
      create a total antihypertensive DDD value. RESULTS: A total of 217 patients (mean
      age = 61.4 +/- 10.2 years; 66% female; 57% black) provided usable HBPM data.
      Among 90 (41%) intensification-eligible hypertensive patients (ie, mean HBPM SBP
      values for 6-months ?135 mm Hg), mean total antihypertensive DDD was increased in
      61% at 12 months. Blacks had significantly higher mean DDD at baseline and 12
      months, but intensification (+0.72 vs +0.65; P = 0.83) was similar by race.
      However, intensification was greater in males than females (+1.1 vs +0.39; P =
      0.031). Reduction in mean SBP following intensification was greater in white
      versus black patients (-8.2 vs -3.9 mm Hg; P = 0.14). Conclusion/Relevance:
      Treatment intensification in HBPM users was similar by race, differed
      significantly by gender, and may produce a greater response in white patients.
      Differential AMI in HBPM users does not appear to contribute to persistent racial
      disparities in BP control.

PMID- 30282469
TI  - PROMIS and FAAM Minimal Clinically Important Differences in Foot and Ankle
      Orthopedics.
AB  - BACKGROUND: Establishing score points that reflect meaningful change from the
      patient perspective is important for interpreting patient-reported outcomes. This
      study estimated the minimum clinically important difference (MCID) values of 2
      Patient-Reported Outcomes Measurement Information System (PROMIS) instruments and
      the Foot and Ankle Ability Measure (FAAM) Sports subscale within a foot and ankle
      orthopedic population. METHODS: Patients seen for foot and ankle conditions at an
      orthopedic clinic were administered the PROMIS Physical Function (PF) v1.2, the
      PROMIS Pain Interference (PI) v1.1, and the FAAM Sports at baseline and all
      follow-up visits. MCID estimation was conducted using anchor-based and
      distribution-based methods. RESULTS: A total of 3069 patients, mean age of 51
      years (range = 18-94), were included. The MCIDs for the PROMIS PF ranged from
      approximately 3 to 30 points (median = 11.3) depending on the methods being used.
      The MCIDs ranged from 3 to 25 points (median = 8.9) for the PROMIS PI, and from 9
      to 77 points (median = 32.5) for the FAAM Sports. CONCLUSIONS: This study
      established a range of MCIDs in the PROMIS PF, PROMIS PI, and FAAM Sports
      indicating meaningful change in patient condition. MCID values were consistent
      across follow-up periods, but were different across methods. Values below the
      25th percentile of MCIDs may be useful for low-risk clinical decisions. Midrange
      values (eg, near the median) should be used for high stakes decisions in clinical
      practice (ie, surgery referrals). The MCID values within the interquartile range
      should be utilized for most decision making. LEVEL OF EVIDENCE: Level I,
      diagnostic study, testing of previously developed diagnostic measure on
      consecutive patients with reference standard applied.

PMID- 30282470
TI  - Meta-Analysis of the Effect of Red on Perceived Attractiveness.
AB  - We conducted meta-analyses of studies that test the red-romance hypothesis, which
      is that the color red enhances heterosexual attraction in romantic contexts. For
      men rating women, we found a small, statistically significant effect ( d = 0.26
      [0.12, 0.40], p = .0004, N = 2,961), with substantial heterogeneity, Q(44) =
      172.5, pQ < .0001, I2 = 89% [82, 94], and equivocal results regarding the
      possibility of upward bias in the estimate. For women rating men, we found a very
      small effect ( d = 0.13 [0.01, 0.25], p = .03, N = 2,739), with substantial
      heterogeneity, Q(35) = 73.0, pQ = .0002, I2 = 53% [33, 80], and evidence of
      upward bias in the estimate. Moderator analyses suggest effect sizes may have
      declined over time (both genders), may be largest when an original shade of red
      is used (men only), and may be smaller in preregistered studies (women only). We
      present contrasting interpretations and suggestions for future research.

PMID- 30282471
TI  - The 'Fit for Life' exercise programme: improving the physical health of people
      with a mental illness.
AB  - People with a mental illness have very poor physical health parameters when
      compared to the general population. This paper outlines an exercise programme
      developed to improve overall fitness and curb weight gain. Seventy-two mental
      health service inpatients completed the general or individualised gym exercise
      programme within 12 weeks. Baseline and end of course physical health parameters
      were recorded, along with test results on a number of fitness, strength and
      agility tasks. No statistically significant differences were found between
      average pre and post programme weight scores, and weight did not increase over
      time. Significant differences were found on strength and agility tasks, and a
      decrease was observed in average resting and post exercise heart rates. Average
      blood pressure did not change, but the number of baseline readings indicating
      hypertension reduced from 14 to 8 people. The exercise programme was successful
      in improving the physical capacity of the individuals who participated.

PMID- 30282472
TI  - Does proximity to the subventricular zone and expression of CXCR-4 and nestin
      affect prognosis in high-grade glioma?
AB  - BACKGROUND: It is suspected that infiltration of stem cell areas with high-grade
      glioma (HGG) generates a population that compromises treatment results and
      survival. In this prospective study we set to assess the prognostic value of the
      proximity of the contrast-enhancing lesion (CEL) on MRI to the subventricular
      zone (SVZ) and the expression of CXCR4 and nestin as potential factors in the
      stem cell migration pathway. METHOD: All patients diagnosed with high-grade
      glioma over a three-year period from a single institution were enrolled in this
      prospective study. Based on MRI preoperative findings, the patients were
      classified into 4 Groups (I-IV) according to the proximity of the CEL on MRI to
      the SVZ. Histological samples were assessed with immunohistochemistry for nestin
      and CXCR4. Classification into groups and the presence of nestin and CXCR4 were
      evaluated as predictive factors for overall (OS) and progression free survival
      (PFS). RESULTS: Fourty patients were included in the study. In multivariate
      analysis, Groups II, III and IV predicted longer OS in comparison to group I (p =
      0.01; p < 0.01; p < 0.01 respectively) and group III and IV predicted longer OS
      in comparison to group II (p < 0.01; p = 0.04 respectively). Group III predicted
      longer PFS than group I and II (p = 0.01; p < 0.01 respectively). The expression
      rates of CXCR-4 and nestin could not predict OS or PFS. CONCLUSIONS: In our study
      the classification according to the proximity of the contrast enhancing part of
      the lesion and the SVZ proved to be prognostically significant for both OS and
      PFS. Presence of CXCR4 or nestin was not predictive for OS or PFS.

PMID- 30282473
TI  - Perceptions of emotional and physical wellness among African American men as
      predictors of perceived overall health.
AB  - African American are at risk for adverse emotional health. However, due to the
      intersection of their racial and gender identities which heightens their
      masculinity, emotional wellness is not always considered a priority by and for
      these men. This study aimed to examine African American men's emotional and
      physical health in relation to their overall health. An exploratory cross
      sectional study was conducted to examine self-reported responses regarding
      emotional and physical health as predictors of overall wellness among a
      convenience sample of 115 African American men. The Wellness Self-Perception
      Questionnaire (WSPQ), a 15-item scale, was used to assess emotional and physical
      wellness. Overall health was assessed by a single item. Of the 115 study
      participants, the majority reported a positive perception of their overall
      health. Linear regression analyses revealed that both reported emotional wellness
      and physical wellness predicted better overall wellness, even when controlling
      for men's education and income. A review of the literature indicates this is the
      first study to assess emotional and physical wellness as predictors of overall
      health for African American men. Since African American men tend to utilize
      physical health services even for mental health concerns, implications for
      physicians are also discussed.

PMID- 30282474
TI  - Fishing-Related Injuries Among Pediatric Patients Treated in United States
      Emergency Departments, 1997 to 2016.
AB  - An estimated 14.8 million youth under the age of 25 years participate in
      recreational fishing. Despite its popularity, fishing can be associated with
      injuries ranging from mild to severe trauma. There is a paucity of research
      available that describes characteristics of fishing-related injuries among youth.
      We examined the National Electronic Injury Surveillance System 1997-2016 to
      describe injury patterns by age and sex. Linear regressions estimated changes in
      injuries over time. There were an estimated 412 171 pediatric patients treated in
      US emergency departments for fishing-related injuries. The majority of injuries
      occurred in males (81.4% [95% confidence interval [CI]: 80.3-82.6]) and in youth
      ages 11 to 18 years (53.7% [95% CI: 51.0-56.5]). Injuries were most likely due to
      hooks and lures (79.7% [95% CI: 75.7-83.7]), and the arm/hand accounted for 43.9%
      of injuries (95% CI: 42.5-45.2). Based on these findings, we suggest that injury
      prevention efforts should be focused on older male children and wearing
      appropriate clothing.

PMID- 30282475
TI  - PROMIS Pain Interference Is Superior vs Numeric Pain Rating Scale for Pain
      Assessment in Foot and Ankle Patients.
AB  - BACKGROUND: The Numeric Pain Rating Scale (NPRS) is a popular method to assess
      pain. Recently, the Patient-Reported Outcomes Measurement Information System
      (PROMIS) has been suggested to be more accurate in measuring pain. This study
      aimed to compare NPRS and PROMIS Pain Interference (PI) scores in a population of
      foot and ankle patients to determine which method demonstrated a stronger
      correlation with preoperative and postoperative function, as measured by PROMIS
      Physical Function (PF). METHODS: Prospective PROMIS PF and PI and NPRS data were
      obtained for 8 common elective foot and ankle surgical procedures. Data were
      collected preoperatively and postoperatively at a follow-up visit at least 6
      months after surgery. Spearman correlation coefficients were calculated to
      determine the relationship among NPRS (0-10) and PROMIS domains (PI, PF) pre- and
      postoperatively. A total of 500 patients fit our inclusion criteria. RESULTS:
      PROMIS PF demonstrated a stronger correlation to PROMIS PI in both the pre- and
      postoperative settings (preoperative: rho = -0.66; postoperative: rho = -0.69)
      compared with the NPRS (preoperative: rho = -0.32; postoperative:rho = -0.33).
      Similar results were found when data were grouped by Current Procedural
      Terminology (CPT) code. CONCLUSION: PROMIS PI was a superior tool to gauge a
      patient's preoperative level of pain and functional ability. This information may
      assist surgeons and patients in setting postoperative functional expectations and
      pain management. LEVEL OF EVIDENCE: Level II, prognostic.

PMID- 30282476
TI  - Diet Quality and High-Sensitivity C-Reactive Protein in Patients With Systemic
      Lupus Erythematosus.
AB  - BACKGROUND AND AIMS: C-reactive protein (CRP) is commonly used as a biomarker for
      inflammation. Mild elevations of CRP have been seen in chronic autoimmune
      diseases like systemic lupus erythematosus (SLE), and CRP has been linked to an
      increased risk of cardiovascular events. Diet quality and certain dietary factors
      seem to influence CRP levels in healthy subjects. To date, the effect of diet on
      serum CRP in SLE has not been studied. Our aim was to investigate the
      relationship between dietary nutrients, antioxidant intake, and serum CRP in SLE.
      DESIGN AND METHOD: A cross-sectional study was conducted among 91 patients with
      SLE. High-sensitivity hsCRP values were determined using an immuno-turbidimetry
      assay in a Beckman Coulter analyzer (AU5800). Dietary intake of macro- and
      micronutrients was assessed through a 24-hr diet recall. Antioxidant nutrient
      intake was evaluated using the dietary antioxidant quality score (DAQs). Linear
      regression models were used to investigate the relationships between serum hsCRP
      levels, dietary nutrient intake, and DAQs. RESULTS: The mean serum hsCRP level
      observed (3.76 +/- 6.68 mg/L) was above the established normal range. However,
      participating SLE patients had low-quality diets, and we found no significant
      correlations between dietary intake of macro- or micronutrients or antioxidant
      nutrient intake (DAQs) and serum CRP levels. CONCLUSION: Our study reveals that
      participating SLE patients had a low-quality diet that did not influence
      inflammatory status measured using serum CRP levels. Further interventional
      studies with high-quality diets in this population are necessary to dissect the
      role of diet on CRP levels in SLE.

PMID- 30282477
TI  - Secreted Heat Shock Protein 90alpha Attenuated the Effect of Anticancer Drugs in
      Small-Cell Lung Cancer Cells Through AKT/GSK3beta/beta-Catenin Signaling.
AB  - Small-cell lung cancer (SCLC) represents the progressive form of lung cancer.
      Patients with SCLC have poor prognosis, partially due to drug resistance.
      Therefore, understanding the underlying mechanism for drug resistance in SCLC is
      needed to improve clinical outcomes. The concentrations of heat shock protein
      90alpha (HSP90alpha) in medium were detected by enzyme-linked immunosorbent
      assay. The protein levels were detected by Western blot. Cell apoptosis was
      detected by propidium iodide staining in cell lines or terminal deoxynucleotidyl
      transferase dUTP nick end labeling staining in tumor sections. Doxorubicin (DOX)
      was administered into cultured cell lines or intraperitoneally injected into
      xenograft mouse to induce apoptosis. In SCLC cell lines, either DOX or ABT-737
      increased extracellular HSP90alpha levels, which attenuated the percentage of
      apoptotic cells. Extracellular HSP90alpha activated Ak strain transforming (AKT)
      and beta-catenin signaling and inhibited glycogen synthase kinase 3beta
      (GSK3beta) signaling. In the xenograft mouse model, extracellular HSP90alpha
      promoted tumor development and inhibited apoptosis of tumor cells. Heat shock
      protein 90alpha attenuates the efficacy of anticancer drugs in SCLC cells through
      AKT/GSK3beta/beta-catenin signaling.

PMID- 30282478
TI  - The Glycosaminoglycan Content of Hip Cartilage in Osteonecrosis of Femoral Head:
      Evaluation with Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of
      Cartilage.
AB  - Objective Hip cartilage quality is essential for the success of joint-preserving
      surgery for osteonecrosis. This study aimed to characterize cartilage changes in
      osteonecrosis of femoral head (ONFH) using delayed gadolinium-enhanced magnetic
      resonance imaging of cartilage (dGEMRIC). Design Fifteen asymptomatic (control)
      and 60 ONFH subjects were included in this study. The ONFH subjects were
      stratified in accordance with the Association Research Circulation Osseous (ARCO)
      classification ( n = 15 hips per ARCO stage). All participant hips were
      investigated using dGEMRIC and theT1Gd data were collected and analyzed. Results
      T1Gd value was significantly lower in the ONFH group (365.1 +/- 90.5 ms; range
      200-498 ms) compared with the control group (546.1 +/- 26.0 ms; range 504-580 ms)
      ( P < 0.001). The T1Gd values of ARCO stage I-IV ONFH were 460.2 +/- 17.3 ms (439
      498 ms), 408.9 +/- 43.4 ms (337-472 ms), 359.9 +/- 34.5 ms (303-412 ms), 231.5 +/
      15.1 ms (200-253 ms), respectively. Decreased T1Gd value was found to correlate
      significantly with increased ONFH severity ( P < 0.001). T1Gd value in collapse
      stage was significantly lower than that of noncollapse stage (295.7 +/- 70.3 ms
      [range 200-412 ms] vs. 434.6 +/- 41.7 ms [range 337-498 ms]; P < 0.001).
      Conclusions dGEMRIC identified hip cartilage as abnormal in ONFH, even at early
      stage, as represented by decreased T1Gd, and this was further aggravated by ONFH
      collapse.

PMID- 30282480
TI  - Does the menstrual cycle affect the multimodal ultrasound tomography?
AB  - Background Multimodal ultrasound tomography (MUT) is a promising new three
      dimensional imaging technology for breast cancer detection without ionizing
      radiation or need for tissue compression. It offers an automatic scan of the
      pendulant whole breast. Purpose As breast tissue properties are affected by the
      menstrual cycle (MC), we examined whether there is an objective difference in the
      refractivity and attenuation images obtained via MUT at different phases of the
      menstrual cycle. Material and Methods Thirteen asymptomatic volunteers (age range
      = 27-44 years) with a regular MC were scanned once weekly for four weeks.
      Attenuation and refractivity images of the breast coronal slices obtained via MUT
      are calibrated against precisely controlled water-through values of the
      ultrasound waves. The average of attenuation and refractivity values measured in
      the MUT images were calculated for each volunteer every week. Results During the
      MC, the weekly averages of the refractivity images for all volunteers were 
      0.650% (week 1), -0.585% (week 2), -0.692% (week 3), and -0.628% (week 4), and
      the corresponding attenuation weekly averages were 1.712 dB/cm, 1.635 dB/cm,
      1.673 dB/cm, and 1.653 dB/cm. There were no statistically significant changes
      during MC. Conclusion Although there are biological changes in breast tissue
      properties during the MC, we did not observe statistically significant changes in
      the average values of MUT refractivity and attenuation images in each breast for
      different weeks of the MC. This finding implies that the diagnostic accuracy of
      the MUT may not be affected by the timing of the scan during the MC.

PMID- 30282479
TI  - Emergency Department Presentations and Youth Suicide: A Case-Control Study.
AB  - OBJECTIVE: We estimate associations between emergency department (ED) diagnoses
      and suicide among youth to guide ED care. METHOD: This ED-based case-control
      study used data from the Office of the Chief Coroner and all EDs in Ontario,
      Canada. Cases ( n = 697 males and n = 327 females) were aged 10 to 25 years who
      died by suicide in Ontario between April 2003 and March 2014, with an ED contact
      in the year before their death. Same-aged ED-based controls were selected during
      this time frame. Crude and adjusted odds ratios (aORs) and 95% confidence
      intervals were calculated. RESULTS: Among youth diagnosed with a mental health
      problem at their most recent ED contact (41.9% cases, 5% controls), suicide was
      elevated among nonfatal self-inflicted: 'other' injuries, including hanging,
      strangulation, and suffocation in both sexes (aORs > 14); cut/pierce injuries in
      males (aOR > 5); poisonings in both sexes (aORs > 2.2); and mood and psychotic
      disorders in males (aORs > 1.7). Among those remaining, 'undetermined' injuries
      and poisonings in both sexes (aORs > 5), 'unintentional' poisonings in males (aOR
      = 2.1), and assault in both sexes (aORs > 1.8) were significant. At least half of
      cases had ED contact within 106 days. CONCLUSIONS: The results highlight the need
      for timely identification and treatment of mental health problems. Among those
      with an identified mental health problem, important targets for suicide
      prevention efforts are youth with self-harm and males with mood and psychotic
      disorders. Among others, youth with unintentional poisonings, undetermined
      events, and assaults should raise concern.

PMID- 30282481
TI  - Arterial embolization for hemoptysis in patients with chronic pulmonary
      tuberculosis and in patients with bronchiectasis.
AB  - Background Previous studies suggest that recurrence of hemoptysis after arterial
      embolization is associated with the underlying pulmonary disease. Purpose To
      compare the baseline information and imaging findings in patients with hemoptysis
      due to either chronic pulmonary tuberculosis (PTB) or bronchiectasis and to
      identify predictors of rebleeding after embolization treatment. Material and
      Methods Clinical data of all consecutive chronic PTB and bronchiectasis patients
      who underwent arterial embolization for hemoptysis from January 2010 to January
      2017 in a single center were reviewed. Baseline clinical information,
      radiological features, and rebleeding rates were compared between patients with
      chronic PTB and patients with bronchiectasis. Multivariate analysis was used to
      identify risk factors of recurrence in each patient group. Results Seventy-six
      patients with chronic PTB and 97 patients with bronchiectasis were included. Male
      sex, pleural thickening, multiple embolized arteries, and non-bronchial systemic
      arterial (NBSA) blood supply were more common in chronic PTB patients. The short
      term and long-term recurrence-free rates were significantly lower in the chronic
      PTB group ( P < 0.001). For the chronic PTB group, the presence of lung
      destruction and shunts were independent predictors of rebleeding during follow
      up. Compared with patients who did not undergo computed tomography angiography
      (CTA) before the procedure, patients with CTA showed less recurrence in the first
      month after treatment ( P = 0.019). Conclusion Chronic PTB patients had more
      extensive NBSA blood supply and experienced higher short- and long-term
      recurrence rates compared with bronchiectasis patients. The risk of rebleeding
      was high in chronic PTB patients with lung destruction and/or shunts.

PMID- 30282482
TI  - The nerve root sedimentation sign in diagnosis of lumbar spinal stenosis.
AB  - Background The nerve root sedimentation sign is a magnetic resonance (MR) sign,
      shown to be present in central lumbar spinal stenosis. The lack of sedimentation
      of the nerve roots to the dorsal part of the dural sac is consistent with the
      positive nerve root sedimentation sign. Purpose To validate the reliability of
      the nerve root sedimentation sign in diagnosis of different grades of lumbar
      spinal canal stenosis. Material and Methods This study was a retrospective review
      of 101 consecutive MR imaging (MRI) studies obtained on patients with clinically
      suspected lumbar canal stenosis. Based on the minimum anteroposterior (AP)
      diameter of the dural sac the study sample was classified into two groups: a
      group with morphological lumbar spinal stenosis; and the group of patients free
      from stenosis (AP > 12 mm). Patients with stenosis were further subclassified
      based on its severity: severe stenosis (AP <= 10 mm); and moderate stenosis (AP >
      10 mm to <= 12 mm). Results Positive sedimentation sign was identified in 81% of
      patients with severe lumbar spinal stenosis and 14% of patients with moderate
      stenosis. No patients without lumbar spinal stenosis had a positive nerve root
      sedimentation sign. Of patients with a positive nerve root sedimentation sign,
      89% presented with neurological claudication. Conclusion The nerve root
      sedimentation is a useful tool for identification of patients with both severe
      clinical and morphological lumbar spinal stenosis; however, its performance in
      the diagnosis of patients with moderate morphological spinal stenosis is poor.

PMID- 30282483
TI  - Evaluation of early treatment response to radiotherapy for HCC using pre- and
      post-treatment MRI.
AB  - Background Stereotactic body radiation therapy is an emerging treatment option
      for patients with unresectable advanced hepatocellular carcinoma (HCC). Because
      liver parenchyma neighboring the tumor is unavoidably exposed to irradiation,
      evaluation of treatment response following radiotherapy for HCC is challenging
      due to increased peritumoral arterial hyperemia and delayed clearance of contrast
      agent in the tumor. Purpose To explore which change of magnetic resonance imaging
      (MRI) features between pre- and post-radiotherapy could help evaluate viability
      of HCC. Material and Methods Thirty-nine patients who underwent MRI before and
      immediately after radiotherapy for HCC were enrolled. Imaging features were
      assessed before and within three months after radiotherapy and changes of those
      imaging features were correlated with (i) tumor response at six months after
      radiotherapy and (ii) time to progression (TTP). Results On post-radiotherapy
      MRI, the short-term responders showed significantly higher incidence of negative
      typical HCC features including arterial enhancement with washout ( P = 0.032),
      hyper-intense T2 signal intensity ( P = 0.021), and hyper-intensity on DWI ( P <
      0.001). On multivariate Cox hazard analysis to estimate TTP, hazard ratios of
      modified RECIST and disappearance of arterial enhancement with washout were 2.18
      and 2.79 ( P = 0.087 and 0.029, respectively). Conclusion Disappearance of
      arterial enhancement with washout on post-radiotherapy would be strong features
      for prediction of treatment response after radiotherapy of HCC.

PMID- 30282484
TI  - Detection of axillary lymph node recurrence in patients with personal history of
      breast cancer treated with sentinel lymph node biopsy (SLNB): results of
      postoperative combined ultrasound and mammography screening over five consecutive
      years.
AB  - Background Sentinel lymph node biopsy (SLNB) has been accepted as the standard
      treatment for axillary evaluation for invasive breast cancer with a clinically
      negative axilla and the low rate of recurrence after SLNB was reported. Purpose
      To evaluate the performance of screening ultrasound (US) for breast and axillary
      recurrence detection in breast cancer patients who underwent SLNB. Material and
      Methods We identified 2807 examinations of 562 breast cancer patients who
      underwent SLNB and received annual screening US combined with mammography (MG)
      for five years. The cancer detection rate, recall rate, and positive predictive
      value (PPV3) of biopsies in breasts and breast plus axillae were calculated
      separately. Results During the five-year follow-up period, 21 patients had
      recurrences of breast cancer (9.8 per 1000 person-year; 95% confidence interval
      [CI] = 6.0-14.9), including three axillary recurrences (1.4 per 1000 person-year;
      95% CI = 0.3-4.1). Screening breast US detected 12 breast cancers. The axillary
      scanning detected none of the axillary recurrences, but yielded 11.8 recalls per
      1000 US screenings; the PPV3 for the breast and breast plus axillae were 18.3%
      and 15.1%, respectively. Conclusion Axillary recurrence was very rare in patient
      who underwent SLNB; additional axillary scanning did not provide axillary
      recurrence detection, but only increased the number of false-positive recalls and
      biopsies.

PMID- 30282485
TI  - Protective effects of quercetin from oxidative/nitrosative stress under
      intermittent hypobaric hypoxia exposure in the rat's heart.
AB  - BACKGROUND: Exposure to high altitude in hypobaric hypoxia (HH) is considered to
      be a physiological oxidative/nitrosative stress. Quercetin (Que) is an effective
      antioxidant and free radical scavenger against oxidative/nitrosative stress.
      AIMS: The aim of this study was to investigate the cardioprotective effects of
      Que in animals exposed to intermittent HH (IHH) and therefore exposed to
      oxidative/nitrosative stress. MATERIALS AND METHODS: Wistar albino male rats were
      exposed to short-term (2 days) or long-term (4 weeks; 5 days/week) IHH in a
      hypobaric chamber (5,500 m, 8 h/day, 380 mmHg, 12% O2, and 88% N2). Half of the
      animals received natural antioxidant Que (body weight: 30 mg/kg) daily before
      each IHH exposure and the remaining rats received vehicle (carboxymethylcellulose
      solution). Control rats were kept under normobaric normoxia (Nx) and treated in a
      corresponding manner. One day after the last exposure to IHH, we measured the
      cardiac hypoxia-induced oxidative/nitrosative stress biomarkers: the
      malondialdehyde (MDA) level and protein carbonyl (PC) content, the activity of
      some antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)], the
      nitrite plus nitrate (NOx) production, and the inducible nitric oxide synthase
      (iNOS) protein expression. RESULTS: Heart tissue MDA and PC levels, NOx level,
      and iNOS expression of IHH-exposed rats had increased, and SOD and CAT activities
      had decreased compared with those of the Nx-exposed rats (control groups). MDA,
      CP, NOx, and iNOS levels had decreased in Que-treated IHH-exposed rats compared
      with IHH-exposed rats (control groups). However, Que administration increased SOD
      and CAT activities of the heart tissue in the IHH-exposed rats. CONCLUSION: HH
      exposure increases oxidative/nitrosative stress in heart tissue and Que is an
      effective cardioprotective agent, which further supports the oxidative cardiac
      dysfunction induced by hypoxia.

PMID- 30282486
TI  - Prenatal hypoxia-ischemia decreases spatial memory and increases aggression
      during adolescence.
AB  - Prenatal hypoxia-ischemia (HI) is a major cause of mortality and chronic
      neurological diseases in newborns. HI contributes to the emergence of several
      neurological disorders such as cognitive and behavioral deficits due to the
      atypical brain development. This study aimed at assessing the effects of prenatal
      HI on the spatial memory and aggression of rats during adolescence. Pregnant rats
      were divided into treatment and control groups. The rats of the treatment groups
      underwent unilateral ligation of the uterine artery on pregnancy day 7, 12, or
      17. The offspring of these rats were tested for spatial memory and aggression
      when they reached 33 days of age. It has been found that the percentages of
      alternations in the Y-maze and the number of crossings in the Morris water maze
      tests of the HI groups were lower than those of the control groups. The total
      offense and defense aggression scores of the HI groups were higher than those of
      the control groups. In conclusion, the longer the duration of HI, the more
      deficits it causes in the spatial memory and aggression of rats during
      adolescence.

PMID- 30282487
TI  - Effects of results-based financing of maternal and child health services on
      patient satisfaction in Afghanistan.
AB  - Objective To examine the impact of a results-based financing programme on patient
      satisfaction in Afghanistan. Methods We analysed data collected from over 3000
      patients from a stratified sample of 112 health facilities (56 results-based
      financing and 56 non-results-based financing) in 11 out of the 34 provinces of
      Afghanistan over a three-year period. The 112 facilities were part of 442 primary
      care facilities that were stratified on facility type and randomly assigned to
      the results-based financing (intervention) and non-results-based financing
      (control) groups in the 11 provinces. Data were obtained from the National Health
      Service Performance Assessment, a baseline survey of patients conducted in 2010,
      and two follow-up surveys in 2011 and 2012. Measurement of patient satisfaction
      used a questionnaire comprising 11 questions concerning overall satisfaction, and
      satisfaction with specific aspects of care, from provider behaviour (e.g.
      respectfulness, communication) to cleanliness, opening hours and waiting times of
      facilities. We used a regression adjusted difference-in-differences estimator to
      investigate the treatment effect on patient satisfaction at facility level.
      Results There were some improvements in patient satisfaction in results-based
      financing facilities but these were not statistically significant. In 2011, 2 out
      of 11 aspects of satisfaction showed 5% improvement: satisfaction with the way
      health care providers explained the patient's condition and treatment. In 2012,
      patient satisfaction was higher for almost all aspects of care in results-based
      financing facilities, including the two aspects on health care provider
      respectfulness and facility opening hours, which had been 5% lower in results
      based financing facilities than in non-results-based financing facilities in
      2011. Overall satisfaction was almost 10% higher in results-based financing
      facilities than in non-results-based financing facilities in 2012. Conclusion
      Even if not statistically significant, observed trends suggest some positive
      impacts of the results-based financing programme on patient satisfaction.

PMID- 30282488
TI  - Designing undergraduate neurosurgical e-learning: medical students' perspective.

PMID- 30282489
TI  - Successful treatment of giant cavernous carotid artery aneurysm in a child using
      a flow diverter stent.
AB  - Giant intracranial aneurysms are extremely rare in children. We present such a
      case, describe angiographic appearances and successful treatment using a flow
      diverter stent.

PMID- 30282490
TI  - Prospective study evaluating post-operative central nervous system infections
      following cranial surgery.
AB  - AIMS: To evaluate the efficacy of our methods for decreasing the incidence of
      post-operative central nervous system infections (PCNSI) and to assess the type
      of microbiology and risk factors associated with PCNSI. METHODS: This prospective
      study was performed at First Affiliated Hospital, College of Medicine, Zhejiang
      University, which is a major medical centre in eastern China. The study included
      adult patients who underwent cranial surgery from January 2014 to October 2015 at
      this institution and survived for more than 7 days . The demographic information
      and clinical data of the patients were recorded for every operation and the
      incidence of PCNSI and the type of microbiology were analysed separately for
      patients undergoing craniotomy and those undergoing cranial burr-hole surgery.
      Prior to initiation of the study, our research team had developed and implemented
      a series of methods for reducing infection rates in our department. RESULTS: A
      total of 1,616 cranial surgery procedures were assessed in the present study;
      1,236 craniotomy/craniectomy operations and 380 cranial burr-hole surgery
      operations. Of these procedures, 29 were complicated by PCNSI (27 cases with
      meningitis/ventriculitis and two with intracranial abscess/empyema). The overall
      incidence of PCNSI was 1.8%, while the incidence of craniotomy/craniectomy
      operations was 2.0% (25 cases) and that of burr-hole surgery operations was 1.1%
      (four cases); the most common microorganism was Staphylococcus. Of the patients
      who underwent cranial burr-hole surgery, the only independent risk factor for
      PCNSI was the absence of prophylactic antibiotics. There were no independent risk
      factors for craniotomy/craniectomy operations. CONCLUSIONS: In the present large
      sample study, the incidence of PCNSI was 1.8%, which was dramatically lower than
      that of a previous study performed by our research group.

PMID- 30282491
TI  - Clinical effect of the proximity of epidural blood patch injection to the leakage
      site in spontaneous intracranial hypotension.
AB  - BACKGROUND: Epidural blood patch (EBP) has been shown to be an effective
      treatment option for spontaneous intracranial hypotension (SIH). We investigated
      whether response to the EBP was related to the distance of the injection site
      from the leakage site in patients with SIH. METHODS: We reviewed patients with
      SIH who underwent EBP at a single hospital. Patients were assigned to group R
      (response after EBP) or group N (no response after EBP). We then analyzed the
      demographics, clinical characteristics, leakage site, leakage length, EBP
      injection level and distance from leakage site, and injected EBP volume. RESULTS:
      Sixty-two patients were included in the analysis. The overall response rate to
      EBP was 59.7% (37 patients). The leakage length and injection distance from the
      leakage site did not differ between the two groups. Age, gender, body mass index,
      leakage site, and EBP volume did not differ significantly between the two groups.
      CONCLUSION: The clinical effect of EBP in SIH was not affected by leakage length
      or injection distance to leakage site. Further large studies must be conducted to
      investigate the efficacy of targeted EBP for SIH.

PMID- 30282492
TI  - Management of advanced heart failure: a review.
AB  - INTRODUCTION: Heart failure (HF) has become a global pandemic. Despite recent
      developments in both medical and device treatments, HF incidences continues to
      increase. The current definition of HF restricts itself to stages at which
      clinical symptoms are apparent. In advanced heart failure (AdHF), it is
      universally accepted that all patients are refractory to traditional therapies.
      As the number of HF patients increase, so does the need for additional
      treatments, with an increased proportion of patients requiring advanced
      therapies. Areas covered: This review discusses extensive evidence for the effect
      of medical treatment on HF, although the data on the effect on AdHF is scare.
      Authors review the relevant literature for treating AdHF patients. Furthermore,
      mechanical circulatory devices (MCD) have emerged as an alternative to heart
      transplantation and have been shown to enhance quality of life and reduce
      mortality therefore authors also review the current literature on the different
      MCD and technologies. Expert commentary: More patients will need advanced
      therapies, as the access to heart transplantation is limited by the number of
      available donors. AdHF patients should be identified timely since the window of
      opportunities for advanced therapy is narrow as their morbidity is progressive
      and survival is often short.

PMID- 30282493
TI  - "Even the fowl has feelings": access to HIV information and services among
      persons with disabilities in Ghana, Uganda, and Zambia.
AB  - BACKGROUND: Persons with disabilities have often been overlooked in the context
      of HIV and AIDS risk prevention and service provision. This paper explores access
      to and use of HIV information and services among persons with disabilities.
      METHODS: We conducted a multi-country qualitative research study at urban and
      rural sites in Uganda, Zambia, and Ghana: three countries selected to exemplify
      different stages of the HIV response to persons with disabilities. We conducted
      key informant interviews with government officials and service providers, and
      focus group discussions with persons with disabilities and caregivers. Research
      methods were designed to promote active, meaningful participation from persons
      with disabilities, under the guidance of local stakeholder advisors. RESULTS:
      Persons with disabilities emphatically challenged the common assumption that
      persons with disabilities are not sexually active, pointing out that this
      assumption denies their rights and - by denying their circumstances - leaves them
      vulnerable to abuse. Among persons with disabilities, knowledge about HIV was
      limited and attitudes towards HIV services were frequently based upon
      misinformation and stigmatising cultural beliefs; associated with illiteracy
      especially in rural areas, and rendering people with intellectual and
      developmental disability especially vulnerable. Multiple overlapping layers of
      stigma towards persons with disabilities (including internalised self-stigma and
      stigma associated with gender and abuse) have compounded each other to contribute
      to social isolation and impediments to accessing HIV information and services.
      Participants suggested approaches to HIV education outreach that emphasise the
      importance of sharing responsibility, promoting peer leadership, and increasing
      the active, visible participation of persons with disabilities in intervention
      activities, in order to make sure that accurate information reflecting the
      vulnerabilities of persons with disabilities is accessible to people of all
      levels of education. Fundamental change to improve the skills and attitudes of
      healthcare providers and raise their sensitivity towards persons with
      disabilities (including recognising multiple layers of stigma) will be critical
      to the ability of HIV service organisations to implement programs that are
      accessible to and inclusive of persons with disabilities. DISCUSSION: We suggest
      practical steps towards improving HIV service accessibility and utilisation for
      persons with disabilities, particularly emphasising the power of community
      responsibility and support; including acknowledging compounded stigma, addressing
      attitudinal barriers, promoting participatory responses, building political will
      and generating high-quality evidence to drive the continuing response.
      CONCLUSIONS: HIV service providers and rehabilitation professionals alike must
      recognise the two-way relationship between HIV and disability, and their multiple
      overlapping vulnerabilities and stigmas. Persons with disabilities demand
      recognition through practical steps to improve HIV service accessibility and
      utilisation in a manner that recognises their vulnerability and facilitates
      retention in care and adherence to treatment. In order to promote lasting change,
      interventions must look beyond the service delivery context and take into account
      the living circumstances of individuals and communities affected by HIV and
      disability. Implications for Rehabilitation Persons with disabilities are
      vulnerable to HIV infection but have historically been excluded from HIV and AIDS
      services, including prevention education, testing, treatment, care and support.
      Fundamental change is needed to address practical and attitudinal barriers to
      access, including provider training. Rehabilitation professionals and HIV service
      providers alike must acknowledge the two-way relationship between HIV and
      disability: people with disability are vulnerable to HIV infection; people with
      HIV are increasingly becoming disabled. Peer participation by persons with
      disabilities in the design and implementation of HIV services is crucial to
      increasing accessibility. Addressing political will (through the National
      Strategic Plan for HIV) is crucial to ensuring long-term sustainable change in
      recognizing and responding to the heightened vulnerability of people with
      disability to HIV.

PMID- 30282494
TI  - Knockdown of activated Cdc42-associated kinase inhibits human extravillous
      trophoblast migration and invasion and decreases protein expression of pho-Akt
      and matrix metalloproteinase.
AB  - INTRODUCTION: The sufficient invasion and migration of human extravillous
      trophoblast (EVTs) cells are crucial for placentation. Inadequate invasion of
      trophoblasts may correlate with the development of preeclampsia. Many studies
      have suggested that activated Cdc42-associated kinase (ACK1) is associated with
      tumor metastasis and invasion. This study investigated the ACK1 expression and
      its function in trophoblasts during placental development. METHODS: ACK1
      expression in human placentas was determined through immunofluorescence. We
      investigated the migration/invasion of the immortalized human first-trimester EVT
      cell line HTR8/SVneo. Hypoxia-reoxygenation (H/R) conditions were applied to
      mimic preeclampsia model in vitro. Lentiviral vector-based short-hairpin RNA
      directed against the sequence of ACK1 (ACK1 shRNA) was used to knock down ACK1
      expression in HTR8/SVneo cells. Cell apoptosis and proliferation were determined
      through flow cytometry and cell counting Kit-8 (CCK-8) assays, respectively. The
      expression of matrix metalloproteinase (MMP) 2/9 and tissue inhibitors of
      metalloproteinase (TIMP) 1/2 was measured by western blotting. RESULTS: ACK1
      localized within trophoblasts of human placental villi, decidual cells in the
      maternal decidua. ACK1 levels in preeclampsia (PE) placentas were significantly
      lower than those in controls. ACK1 shRNA significantly inhibited HTR8/SVneo cells
      migration and invasion but did not affect their apoptosis and proliferation. ACK1
      knockdown decreased MMP2/9 and increased TIMP1/2 expression, as well as
      downregulated the phosphorylation of AKt (p-Akt). In addition, ACK1 and MMP2/9
      were downregulated following treatment with LY294002, whereas ACK1 shRNA had no
      effect on phosphorylation of PI3K(p-PI3K). After exposed in H/R condition, ACK1
      expression, MMP2/9 protein, and p-Akt were also significantly decreased.
      DISCUSSION AND CONCLUSIONS: ACK1 expression is lowered in preeclamptic placentas
      and promotes trophoblast cell invasion, migration. H/R conditions decrease ACK1
      expression and appear to decouple the positive relationship between ACK1
      expression and Akt activation.

PMID- 30282495
TI  - Future of Biologics in Healing Angiopathic Wounds.

PMID- 30282496
TI  - A Simple Whole-Blood Polymerase Chain Reaction without DNA Extraction for
      Thalassemia Diagnosis.
AB  - Polymerase chain reaction (PCR) diagnosis of thalassemia usually relies on using
      genomic DNA. Preparing the genomic DNA can lead to sample-to-sample
      contamination. This report was aimed to establish the PCR protocol using whole
      blood for detecting mutations of alpha- and beta-globin genes causing the
      thalassemia syndrome. First, the PCR facilitators, betaine and bovine serum
      albumin (BSA), were tested, simultaneously with an adjustment of PCR thermal
      cycler and of whole-blood volume. Thereafter, the established whole-blood PCR was
      applied for detecting, in both known and unknown samples, the HBA1 Southeast
      Asian (- -SEA) (NG_000006.1: g.26264_45564del19301) deletion, Hb Constant Spring
      (Hb CS, HBA2: c.427T>C, alphaCSalpha), codon 17 (A>T) (HBB: c.52A>T), codons
      41/42 (-TTCT) (HBB: c.126_129delCTTT) deletion, -28 (A>G) (HBB: c.-78A>G) and
      codon 26 (G>A) (Hb E or HBB: c.79G>A). It was shown that the whole-blood PCR
      worked successfully in 9.0% (w/v) betaine, with 1 MUL of EDTA whole blood and
      with addition of 10 heat-cool steps (3 min. at 94  degrees C, followed by 3 min.
      at 55  degrees C) prior to the typical thermal cycles for the mutations. The
      capability of the new whole-blood PCR was similar to that of the typical DNA
      based PCR. Therefore, the newly established whole-blood PCR could be performed
      for PCR diagnosis of thalassemia. Using this platform, sample-to-sample
      contamination should be eliminated.

PMID- 30282497
TI  - Home Care in Ontario: Perspectives on Equity.
AB  - Home care is an integral aspect of the Canadian health care system. Services
      provided to individuals allow them to live with independence and dignity within
      the comfort of their own residences. This article examines the historical
      evolution of Ontario's home care reform and the current challenges faced by staff
      members, patients, and their caregivers in reference to health equity. Political
      economy and feminist lenses are used to highlight the impact of market-based
      health care reforms on gendered experiences and access to home care services.
      Research and reports are used to critique the development of the home care system
      to date. Findings suggest that the current home care system is underfunded,
      understaffed, and inequitable in access to care. At this time, policies
      strategically remain blinded to the harsh realities of the home care sector in
      order to justify cost cutting, deregulation, and privatization of services.

PMID- 30282500
TI  - Using preferred fluids and different reward schedules to motivate rhesus macaques
      ( Macaca mulatta) in cognitive tasks.
AB  - Rhesus macaques ( Macaca mulatta) used in behavioural neuroscience are often
      required to complete cognitively complex tasks, for which a high level of
      motivation is essential. To induce motivation, researchers may implement fluid
      restriction protocols, whereby freely available water is limited, such that fluid
      can be used as a reward in the laboratory. A variety of different rewards and
      schedules are used, but there exists a lack of data assessing their
      effectiveness. In this study, we aimed to quantify fluid preference in rhesus
      macaques and to use these preferences to compare the motivational quality of
      different reward schedules: the monkey's previous reward (i.e. the fluid used to
      reward them in past studies), their new preferred reward, a variable schedule of
      previous and preferred reward, and a choice between the previous and preferred
      rewards. We found that it may be possible to reduce the level of restriction if
      an adequately motivating preferred reward is identified, but that this is
      dependent on the animal. Each monkey responded differently to both the fluid
      preference assessments and to the different reward schedules. As such, monkeys
      should not be subject to 'blanket' protocols but should be assessed individually
      to maintain adequate scientific data collection at the least severe level of
      fluid restriction.

PMID- 30282499
TI  - HIV blocks Type I IFN signaling through disruption of STAT1 phosphorylation.
AB  - This study investigates the modulation of Type I IFN induction of an antiviral
      state by HIV. IFNs, including IFN-alpha, are key innate immune cytokines that
      activate the JAK/STAT pathway leading to the expression of IFN-stimulated genes.
      IFN-stimulated gene expression establishes the antiviral state, limiting viral
      infection in IFN-alpha-stimulated microenvironments. Our previous studies have
      shown that HIV proteins disrupt the induction of IFN-alpha by degradation of IFN
      beta promoter stimulator-1, an adaptor protein for the up-regulation and release
      of IFN-alpha into the local microenvironment via the retinoic acid-inducible gene
      1-like receptor signaling pathway. However, IFN-alpha is still released from
      other sources such as plasmacytoid dendritic cells via TLR-dependent recognition
      of HIV. Here we report that the activation of the JAK/STAT pathway by IFN-alpha
      stimulation is disrupted by HIV proteins Vpu and Nef, which both reduce IFN-alpha
      induction of STAT1 phosphorylation. Thus, HIV would still be able to avoid
      antiviral protection induced by IFN-alpha in the local microenvironment. These
      findings show that HIV blocks multiple signaling points that would lead to the up
      regulation of IFN-stimulated genes, allowing more effective replication in IFN
      alpha-rich environments.

PMID- 30282498
TI  - Surgical management of coincidental metastases to upper cervical spine and skull
      from hepatocellular carcinoma: a case report.
AB  - Metastases to the skull or upper cervical spine from hepatocellular carcinoma
      (HCC) are very rare. We herein report a unique case of two-site surgery for both
      skull and upper cervical spine metastases from HCC. The patient was a 64-year-old
      man with cervical pain. Computed tomography (CT) revealed osteolytic change
      related to metastatic cervical spine and occipital bone tumors. Two-stage surgery
      involving posterior occipitocervical fusion and occipital bone tumor resection
      was performed. The patient's pain decreased in severity, and postoperative
      radiotherapy and chemotherapy could be conducted. The postoperative course was
      favorable, and the patient exhibited improvement in his activities of daily
      living. Neither cervical spine X-ray examination nor CT showed any
      instrumentation failure, such as screw loosening, before the patient died of
      liver failure 13 months after surgery. Patients with both skull and upper
      cervical spine metastases from liver cancer may have a markedly unfavorable
      prognosis. Even in these patients, however, surgery as an aggressive palliative
      treatment may prolong the survival period or maintain the quality of life as long
      as the patient's general condition permits.

PMID- 30282501
TI  - Peripheral arterial tonometry and angiogenic biomarkers in preeclampsia.
AB  - OBJECTIVE: To evaluate changes in vascular function and serum biomarkers in women
      with and without preeclampsia (PE) to create a model for the easier and more
      precise diagnosis of PE in the future. METHODS: Endothelial function and arterial
      stiffness were evaluated using peripheral arterial tonometry and concentrations
      of placental growth factor (PlGF), soluble fms like tyrosine kinase 1 (sFlt-1)
      and soluble endoglin (sEng) were determined by immunoassay. RESULTS: Arterial
      stiffness deteriorates and endothelial function is better in women with PE
      compared with a healthy pregnancy. Women who developed PE had a decreased PlGF
      and PlGF/(sFlt-1+ sEng) ratio and an increased sEng, and sFlt-1/PlGF ratio.
      CONCLUSION: Peripheral arterial analysis did provide additional information
      beyond serum biomarkers in the diagnosis of PE.

PMID- 30282503
TI  - Bipolar osteoarticular reconstruction of the radioscaphoid joint.

PMID- 30282502
TI  - Prognostic value of pretreatment prognostic nutritional index in non-small cell
      lung cancer: A systematic review and meta-analysis.
AB  - BACKGROUND:: The pretreatment prognostic nutritional index has been considered a
      potential prognostic biomarker in patients with non-small cell lung cancer
      (NSCLC), but this remains controversial. Therefore, we performed a meta-analysis
      to systematically assess the prognostic value of the prognostic nutritional index
      in patients with NSCLC. METHODS:: We systematically searched PubMed, EMBASE, Web
      of Science, and CNKI. The hazard ratios (HRs) with their corresponding 95%
      confidence intervals (CIs) were used to evaluate the link between the prognostic
      nutritional index and the oncological outcomes of patients with NSCLC, including
      overall survival, disease-free survival/recurrence-free survival, and progression
      free survival. RESULTS:: Fifteen studies were included in this meta-analysis.
      Twelve of these studies explored the association between the prognostic
      nutritional index and the overall survival of patients with NSCLC. Our pooled
      analysis indicated that a low prognostic nutritional index was significantly
      related to adverse overall survival (HR 1.61; 95% CI 1.44, 1.81; P < 0.001). Our
      results also showed that the prognostic nutritional index was a negative
      predictor for disease-free survival/recurrence-free survival, and progression
      free survival in patients with NSCLC. CONCLUSION:: Our meta-analysis demonstrated
      that there was a close association between the prognostic nutritional index value
      and prognosis in NSCLC patients and that the prognostic nutritional index may act
      as a useful prognostic biomarker in NSCLC patients.

PMID- 30282504
TI  - Synchronous microsurgical anastomosis in complex replantation surgery.
AB  - We conducted a retrospective case control study of digital replantations in 16
      patients from September 2015 to January 2017. Half of the patients were treated
      by a synchronous microsurgical technique and the other half underwent
      conventional micro-anastomoses. The total time for anastomoses, total operation
      time and survival of digits were the major endpoints in this study. The number of
      digits replanted and the anastomosis method had significant effects on total
      anastomosis time. The mean anastomosis time for each digit was 46 min and 70 min
      in the synchronous and conventional groups, respectively, a 34% reduction in
      anastomosis time in the synchronous group when compared with the conventional
      group. Patency rates were 87% (13/15) of all the digits replanted in each group.
      Level of evidence: IV.

PMID- 30282505
TI  - MRI at term equivalent age for predicting long term neuro-developmental outcome
      in preterm infants - A cohort study.
AB  - INTRODUCTION: Preterm infants are at increased risk of adverse neuro
      developmental outcome (NDO). Cranial ultrasound has limited predictability. The
      aim of the study is to evaluate whether MRI done at term equivalent age (TEA)
      predicts NDO at 18-22 months of corrected gestational age (CGA). METHOD: This
      cohort study of preterm infants born at <= 32 weeks of gestation and/or birth
      weight < 1500 grams between April 2011 and August 2012, was conducted in a
      tertiary care institute in India. MRI done at TEA was reported using objective
      scoring. NDO at 18-22 months CGA was assessed using Bayley Scale of Infant
      Development version III (BSID) III. Composite score (CS) < 85 in motor, language
      or cognition domain was taken as adverse NDO. Association between individual MRI
      subscores and NDO was evaluated using multiple linear regressions by backward
      elimination method. Validity of MRI abnormality in predicting adverse NDO was
      assessed. RESULTS: Out of 94 infants who had MRI at TEA, 56 (60%) underwent BSID
      III. Mean gestational age was 29.8 +/- 2.1 weeks. Median score of all domains
      were lower with higher total MRI score. Predictive accuracy for various subscores
      ranged from 55 to 73%. By multiple regression analysis, signal abnormality was
      associated with motor delay (beta -8.4; p 0.02) and cystic white matter (WM)
      changes with motor delay (beta -7.3; p 0.003) and cognitive delay (beta -6.1; p
      0.005). CONCLUSIONS: Although specificity and negative predictive value were
      moderate to high across all subscores in MRI to predict the NDO, the accuracy has
      been only low to moderate, which limits its use as sole predictor.

PMID- 30282506
TI  - Embracing Transparency Through Data Sharing.
AB  - Low rates of reproducibility and translatability of data from nonclinical
      research have been reported. Major causes of irreproducibility include oversights
      in study design, failure to characterize reagents and protocols, a lack of access
      to detailed methods and data, and an absence of universally accepted and applied
      standards and guidelines. Specific areas of concern include uncharacterized
      antibodies and cell lines, the use of inappropriate sampling and testing
      protocols, a lack of transparency and access to raw data, and deficiencies in the
      translatability of findings to the clinic from studies using animal models of
      disease. All stakeholders-academia, industry, funding agencies, regulators,
      nonprofit entities, and publishers-are encouraged to play active roles in
      addressing these challenges by formulating and promoting access to best practices
      and standard operating procedures and validating data collaboratively at each
      step of the biomedical research life cycle.

PMID- 30282507
TI  - A microcomputed tomography evaluation of the shaping ability of three thermally
      treated nickel-titanium rotary file systems in curved canals.
AB  - Objective To evaluate the shaping ability of three thermally-treated rotary
      nickel-titanium (NiTi) systems including ProTaper Next (PTN), HyFlexTM CM (HFCM)
      and HyFlexTM EDM (HFEDM) during root canal preparation in simulated root canals.
      Methods A total of 45 simulated root canals were divided into three groups ( n =
      15) and prepared with PTN, HFCM or HFEDM files up to size 25. Microcomputed
      tomography (microCT) was used to scan the specimens before and after
      instrumentation. Volume and diameter changes, transportations and centring ratios
      at 11 levels of the simulated root canals were measured and compared. Results
      HFEDM caused significantly greater volume increases than HFCM and PTN in the
      entire root canal and in the apical and middle thirds. HFCM removed the least
      amount of resin in the coronal third compared with HFEDM and PTN. Overall, HFCM
      caused significantly less transportation in the apical 2 mm and was better
      centred than PTN in the apical 3 mm. Conclusion Under the conditions of this
      study, all systems prepared curved canals without significant shaping errors and
      instrument fracture. PTN and HFCM cut less resin than HFEDM. HFCM stayed centred
      apically and cut the least material coronally.

PMID- 30282509
TI  - Medical students' reflective writings about challenging patient encounters: A
      final year medical students perspective.

PMID- 30282510
TI  - The Use of a Novel Super-Oxidized Solution on Top of Standard Treatment in the
      Home Care Management of Postsurgical Lesions of the Diabetic Foot Reduces
      Reinfections and Shortens Healing Time.
AB  - There are still many unmet needs in the treatment of chronic wounds, especially
      regarding microenvironment modulation. Nexodyn is a novel super-oxidized solution
      capable of contrast bacterial proliferation. We aimed to evaluate if this
      solution, on top of standard of care, was safe and effective in improving
      diabetic foot outcome. We selected 50 patients admitted in our department to be
      submitted to surgery for acute diabetic foot infection. All patients were left
      open to heal for secondary intent. We divided patients into 2 groups: Group A (n
      = 25, male/female = 17/8, age = 67.3 +/- 12.1 years, hemoglobin A1C = 7.9 +/-
      1.1%), patients treated with standard of care and, on top of this, Nexodyn
      solution, and Group B, treated only with standard of care. After discharge,
      patients continued Nexodyn application. We followed up patients until complete
      healing or up to 6 months. No differences between groups in healing rate, while
      time required for complete healing was significantly shorter in Group A (64.9 +/-
      12.1 days vs 147.4 +/- 23.1 days, P < .01). During follow-up, the group treated
      with Nexodyn showed a reduced rate of reinfections (12 patients in Group B vs 3
      patients in Group A, P < .05) and of further debridement procedures (1 patient in
      Group A vs 10 patients in Group B, P < .05). Nexodyn provided effective
      protection against reinfections in diabetic foot patients, thus reducing the
      necessity for debridement procedures and their healing time and presents a safety
      profile similar to saline solution.

PMID- 30282508
TI  - Differences in secretome in culture media when comparing blastocysts and arrested
      embryos using multiplex proximity assay.
AB  - OBJECTIVES: The aim of this study was to assess different patterns of the human
      embryo secretome analysed as protein levels in culture media. Furthermore,
      analyses to correlate protein levels with quality and timing to development of
      human embryos were performed. MATERIAL AND METHODS: Human day-2 cryopreserved
      embryos were cultured for four days in an EmbryoScope(r) with a time-lapse
      camera, and embryo quality was evaluated retrospectively. After culture, the
      media were collected and relative levels of secreted proteins were analysed using
      Proseek Multiplex Assays. Protein levels were evaluated in relation to timing to
      development and the ability to form a blastocyst. RESULTS: Specific patterns of
      timing of development of blastocysts were found, where a difference in time to
      start of cavitation was found between high- and low-quality blastocysts. There
      appeared to be a correlation between specific protein patterns and successful
      formation of morulae and blastocysts. Embryos developing into blastocysts had
      higher levels of EMMPRIN than arrested embryos, and levels of caspase-3 were
      lower in high- versus low-quality blastocysts. Also, higher levels of VEGF-A, IL
      6, and EMMPRIN correlated with shorter times to morula formation. CONCLUSIONS:
      The secretome and timing to development differ in embryos forming blastocysts and
      those that become arrested, and in high- versus low-quality blastocysts. The
      levels of certain proteins also correlate to specific times to development.

PMID- 30282511
TI  - Has the implementation of the Minamata convention had an impact on the practice
      of operative dentistry in Jordan?
AB  - Objective To assess Jordanian dentists' current perception and attitudes towards
      amalgam and composite restorations four years after the Minamata treaty was
      endorsed and suggest decision making factors that may influence the type of
      restoration requested by patients. Methods The cross-sectional study was
      conducted through structured questionnaires distributed to dentists in Amman,
      Jordan from June 2017 to February 2018. Results Of the 1686 dentists who were
      contacted 758 dentists (response rate 45%) responded to the questionnaire either
      by email or via field visits. Jordanian dentists used more composite restorations
      than amalgam. Recurrent caries followed by fracture of the restoration were the
      main reasons for replacement of both fillings by dentists. However, dentists
      suggested that the main reason patients requested replacement of amalgam was for
      'staining'. In addition, a large proportion of the dentists had experienced
      patients who had asked either for replacement of amalgam (77%) or refused an
      amalgam filling (99%) for aesthetic reasons. In the opinion of the dentists, only
      20% patients requested replacement of amalgam because of the mercury content.
      Conclusion The findings of this survey suggest that a 'phase-down' of dental
      amalgam is being implemented in Jordan's dental clinics but it is not associated
      with commitment to the Minamata Convention, rather to current dental practice
      trends and patients' aesthetic demands.

PMID- 30282512
TI  - Continuing Clozapine Treatment in Acute Psychosis With Neutropenia.

PMID- 30282513
TI  - Resting-State Functional Connectivity of the Habenula in Mood Disorder Patients
      With and Without Suicide-Related Behaviors.
AB  - The habenula is a small midbrain structure that is important for brain signaling
      and learning from negative events. Thus, the habenula is strongly connected to
      both the reward system and motor regions. Increasing evidence suggests a role for
      the habenula in the etiology of psychiatric disorders, including mood and
      substance use disorders. However, no studies to date have investigated habenular
      resting-state functional connectivity (rsFC) in suicide-related behaviors (SB).
      The authors enrolled 123 individuals with major depressive disorder (MDD) or
      bipolar disorder and a history of suicide-related behaviors (SB+), 74 individuals
      with MDD or bipolar disorder and a history of suicidal ideation but no history of
      SB (SB-), and 75 healthy control subjects (HC). A seed-based approach was used to
      identify regions showing different rsFC with the habenula followed by region of
      interest to region of interest post hoc comparisons. Compared with both the SB-
      and HC groups, the SB+ group showed higher connectivity between the left habenula
      and the left parahippocampal gyrus, the right amygdala, and the right precentral
      and postcentral gyri. Patients with mood disorders displayed higher rsFC between
      the left habenula and left middle temporal gyrus, the left angular gyrus, and the
      left posterior cingulate cortex, as well as lower rsFC between the right habenula
      and the left thalamus, when compared with HCs. These findings suggest that the
      habenula is involved in the neural circuitry of suicide. The higher habenular
      rsFC found in the SB+ group may mediate a dysfunction in the mechanism that links
      the habenula with motor activity and contextual associative processing.

PMID- 30282514
TI  - Delirium Resulting From Traumatic Brain Injury as an Acute Risk Factor for
      Suicide: A Case Report and Review of the Literature.

PMID- 30282515
TI  - Thrombophilic risk factors are laterally associated with Apolipoprotein E gene
      polymorphisms in deep vein thrombosis patients: An Indian study.
AB  - Introduction Deep vein thrombosis is a multifactorial disease with many acquired
      and genetic risk factors. Polymorphism in the APOE gene is an upcoming potential
      pathogenic factor whose role is unclear in deep vein thrombosis. Methods An equal
      number of deep vein thrombosis cases and controls (N = 100, each) were
      investigated for APOE gene polymorphisms along with known acquired and
      hereditable thrombophilic risk factors. APOE genotyping was done by polymerase
      chain reaction. Results The epsilon3/epsilon4 and epsilon2/epsilon3 APOE
      genotypes were commoner in deep vein thrombosis cases than controls but not
      statistically significant ( epsilon3/epsilon4 -> 18% versus 11%, OR = 1.776, CI =
      0.792-3.984, p = 0.16; epsilon2/epsilon3 ->10% versus 9%, OR = 1.123, CI = 0.436
      2.895, p = 0.809). However, the following risk factors were found to be laterally
      associated with APOE genotypes in cases of deep vein thrombosis: pregnancy with
      epsilon2/epsilon3 genotype positivity (N = 29; p = 0.019), recurrent pregnancy
      loss with epsilon3/epsilon3 genotype (N = 29; p = 0.016), normal antithrombin
      levels with epsilon3/epsilon3 genotype (N = 62; p = 0.03) and non-O blood group
      with epsilon3/epsilon4 genotype (N = 100; p = 0.023). Conclusion APOE genotypes
      have shown only a modest association with deep vein thrombosis and were not
      statistically significant. A lateral association of these genotypes with
      thrombophilic risk factors was observed which may be investigated further for the
      possible pathogenetic mechanisms and their therapeutic implications.

PMID- 30282516
TI  - Dietary factors and their association with childhood obesity in the Middle East:
      A systematic review.
AB  - BACKGROUND: Childhood obesity is a global epidemic that is related to
      environmental and genetic factors and has adverse consequences throughout life,
      being obese is a serious health problem in childhood and increases the risk of
      many co-morbidities. AIM: The purpose of this systematic review is to illustrate
      that dietary factors correlate with obesity among children studied in the Middle
      East area. METHODS: Studies were screened by searching two databases in August
      2017 and considered as eligible for inclusion if they: (a) are observational
      studies, (b) define at least one dietary factor for obese children aged 6-12
      years, (c) are undertaken in the Middle East area, and (d) are written in
      English. The search dependent words and terms used are: diet, nutrition,
      pediatric obesity, physical activity, Middle East, overweight, children, excess
      weight, childhood, obesity and dietary factors. Papers were initially evaluated
      for eligibility based on title and abstract. The full text of articles of studies
      that met, or appeared to meet, the inclusion criteria, were saved. Quality
      assessment was conducted using the NIH tool for observational cohort and cross
      sectional studies. Out of 730 studies, 4 papers met the inclusion criteria and
      rated as good quality. These studies were from Iran ( n=2), Saudi Arabia ( n=1)
      and Lebanon ( n=1) during 2008 and 2016. RESULTS: Dietary factors identified were
      breakfast intake, junk-food consumption, energy intake and micronutrient intake.
      The present systematic review shows that several dietary behaviors such as
      missing breakfast, excessive fat and refined carbohydrate intake with low
      micronutrient intake due to low consumption of fruits, vegetables and milk/diary,
      are associated with obesity in children in the Middle East. CONCLUSIONS: A
      healthy diet during childhood to control weight and prevent obesity is
      recommended for a healthy, lifelong adulthood.

PMID- 30282517
TI  - Age-related changes in word retrieval vary by self-reported anxiety but not
      depression symptoms.
AB  - Tip-of-the-tongue states (TOTs) are known to increase in frequency across
      adulthood, but there is wide variability in older adults' TOT rates, suggesting
      that individual difference factors contribute to TOT incidence. We investigated
      the role of affect by examining the relationship between self-reported anxiety
      and depression symptoms and the frequency of TOTs during a laboratory task.
      Participants were young, middle-aged and older adults in a population-based
      sample of adults aged 18-87. Increased anxiety was associated with fewer TOTs for
      the middle-aged group but more TOTs for the older adult group. There was no
      relationship between anxiety and TOTs for younger adults and no relationships
      between depression symptoms and TOT incidence for any age group. We discuss our
      results in terms of attentional control theory, which provides an explanation of
      how age may affect the relationship between anxiety and TOTs.

PMID- 30282519
TI  - Two case reports of Wellens' syndrome.
AB  - Wellens' syndrome is characterised by particular changes in electrocardiogram
      (ECG) precordial lead T-waves accompanied by proximal stenosis of the left
      anterior descending (LAD) artery. Two cases of electrocardiographic changes
      associated with Wellens' syndrome are presented here. Case 1, a 55-year-old
      female, was transferred to the First Affiliated Hospital of Xi'an Jiaotong
      University with intermittent and laborious angina pectoris. Her first ECG on
      admission revealed T-wave inversion in leads V1-V3 and biphasic T-waves in V4.
      Case 2, an 85-year-old female, presented with dyspnoea and paroxysmal chest pain.
      Her admission ECG displayed asymmetrical T-wave inversion in leads V1-V3, I, and
      aVL, and depressed ST segments in leads V2-V5. In this patient, drug-eluting
      stents were placed on a LAD artery lesion and right coronary artery occlusion.
      The potential of ECGs to aid decision-making in severe myocardial infarction is
      straightforward, particularly in patients with characteristic ECGs, however,
      Wellens' syndrome has a wide spectrum of clinical manifestations and the ECG
      patterns may manifest itself persistently over a period of weeks. Therefore, ECG
      parameters should be combined with coronary angiography to confirm the presence
      of lesions.

PMID- 30282518
TI  - Immune response and differentially expressed proteins in the lung tissue of
      BALB/c mice challenged by aerosolized Brucella melitensis 5.
AB  - OBJECTIVE: This study was performed to develop a murine aerosol infection model
      of brucellosis to investigate the pathogenicity and immune reactions induced by
      aerosolized Brucella and to identify key proteins associated with Brucella
      infection in lung tissue. METHODS: BALB/c mice were exposed to aerosolized
      Brucella melitensis 5 (M5) for 30 minutes and killed at 1, 3, 7, and 15 days post
      exposure. Clinical observation, pathological analysis of lung tissue, and
      cytokine expression detection were then performed. Proteomic analysis based on
      two-dimensional electrophoresis and mass spectrometry was used to identify
      proteins exhibiting significant changes in expression in lung tissues during
      Brucella infection. RESULTS: Pathological analysis revealed alveolar wall
      thickening, telangiectasia with hyperemia, inflammatory cell infiltration, large
      areas of congestion and bleeding, and areas of focal necrosis. The T-helper 1
      type immune response played an important role during aerosol infection, and 12
      differentially expressed proteins were involved in the infectious process in lung
      tissue. CONCLUSION: These results contribute to our understanding of the
      pathogenic process of Brucella in the lung tissue of BALB/c mice challenged with
      aerosolized Brucella. Some of the identified proteins may be potential targets in
      future therapeutic strategies.

PMID- 30282520
TI  - Effect of once-only flexible sigmoidoscopy screening on the outcomes of
      subsequent faecal occult blood test screening.
AB  - Objective To investigate the outcomes of biennial guaiac faecal occult blood test
      (gFOBT) screening after once-only flexible sigmoidoscopy (FS) screening. Methods
      Between 1994 and 1999, as part of the UK FS Screening Trial (UKFSST), adults aged
      55-64 were randomly allocated to an intervention group (offered FS screening) or
      a control group (not contacted). From 2006, a subset of UKFSST participants
      (20,895/44,041 intervention group; 41,497/87,149 control group) were invited to
      biennial gFOBT screening by the English Bowel Cancer Screening Programme. We
      analysed gFOBT uptake, test positivity, yield of colorectal cancer (CRC), and
      positive predictive value (PPV) for CRC, advanced adenomas (AAs), and advanced
      colorectal neoplasia (ACN: AA/CRC). Results Uptake of gFOBT at first invitation
      was 1.9% lower (65.7% vs. 67.6%, p < 0.01) among intervention versus control
      group participants. Positivity was 0.4% lower (2.0% vs. 2.4%, p < 0.01) and CRC
      yield was 0.08% lower (0.19% vs. 0.27%, p = 0.14). PPVs were also lower in the
      intervention versus control group, at 10.3% vs. 12.3% ( p = 0.44) for CRC, 22.7%
      vs. 31.4% ( p < 0.01) for AA, and 33.0% vs. 43.7% ( p < 0.01) for ACN. Among
      those who refused FS ( n = 5532), gFOBT uptake at first invitation was 47.7%, CRC
      yield was 0.25%, and PPV for ACN was 46.2%. Among FS attenders ( n = 15,363),
      uptake was 72.2%, CRC yield was 0.18%, and PPV for ACN was 27.9%. Conclusions
      Uptake, positivity and PPV of gFOBT screening were reduced following prior offer
      of FS screening. However, a quarter of FS screened participants receiving a
      diagnostic examination after positive gFOBT were diagnosed with ACN.

PMID- 30282521
TI  - Hospital Practices for Parents Following Perinatal Loss.
AB  - The aim of this study is to provide comprehensive and current information on
      hospital practices following perinatal death. The provinces with the highest
      number of hospitals in Turkey were selected for the study. To collect data, the
      questionnaire form of Canadian hospitals maternity policies and practices survey
      was sent to the appropriate respondents in hospitals. The study showed that
      encouraging parents to have photos of the deceased baby and preparing a
      remembrance pack were the most problematic issues and were not available at the
      majority of hospitals. The most common supportive practices in hospitals were the
      opportunity to see the deceased baby, assisting with funeral options and
      autopsies, and support for completing the necessary legal documents. The result
      indicated that hospitals implement varied practices in assisting the bereaved
      parents. The study recommended developing hospital policies and practices related
      to perinatal death and supporting families during their loss and grief.

PMID- 30282522
TI  - Feature binding in short-term memory and long-term learning.
AB  - In everyday experience, we encounter visual feature combinations. Some
      combinations are learned to support object recognition, and some are arbitrary
      and rapidly changing, so are retained briefly to complete ongoing tasks before
      being updated or forgotten. However, the boundary conditions between temporary
      retention of fleeting feature combinations and learning of feature bindings are
      unclear. Logie, Brockmole, and Vandenbroucke demonstrated that 60 repetitions of
      the same feature bindings for change detection resulted in no learning, but clear
      learning occurred with cued recall of the feature names. We extended those
      studies in two new experiments with the same array of colour-shape-location
      combinations repeated for 120 trials. In Experiment 1, change detection was well
      above chance from Trial 1, but improved only after 40 to 60 trials for
      participants who subsequently reported becoming aware of the repetition, and
      after 100 to 120 trials for participants reporting no awareness. Performance
      improved rapidly in Experiment 2 when participants reconstructed the array by
      selecting individual features from sets of colours, shapes, and locations. All
      participants subsequently reported becoming aware of the repetition. We conclude
      that change detection involves a visual cache memory that functions from the
      first trial, and retains feature bindings only for the duration of a trial. In
      addition, a weak residual episodic memory trace accumulates slowly across
      repetitions, eventually resulting in learning. Reconstructing feature
      combinations generates a much stronger episodic memory trace from trial to trial,
      and so learning is faster with performance supported both by the limited capacity
      visual cache and learning of the array.

PMID- 30282523
TI  - Binding of Platinum Derivative, Oxaliplatin to Deoxyribonucleic Acid: Structural
      Insight into Antitumor Action.
AB  - Platinum derived chemodrugs constitute an active class in cancer therapeutics.
      Besides being potent against various solid tumors, oxaliplatin has been
      recognized as first platinum compound to be approved for the treatment of
      colorectal cancer. Structurally, oxaliplatin consists of a platinum metal
      complexed to oxalate and diaminocyclohexane (DACH) and exert its anticancer
      action by inhibiting DNA replication and transcription. The present study
      highlights the binding properties of oxaliplatin with calf thymus DNA using
      spectroscopic methods to comprehend its binding mechanism at molecular level to
      overcome associated cellular resistance and side-effects. Attenuated total
      reflection-Fourier transform infrared (ATR-FTIR) spectroscopic outcomes confirm
      that oxaliplatin is a covalent binding agent and also provide sequence
      specificity in DNA molecule. Infrared spectral results further indicate that
      oxaliplatin alkylates purine nitrogenous bases majorly guanine residues (G) in
      the major groove via formation of either interstrand or intrastrand guanine
      guanine d(GpG) and guanine-adenine d(GpA) (N7 position) crosslinks accompanied
      with slight external binding to sugar-phosphate backbone. Again, circular
      dichroism (CD) spectroscopic results suggest subtle conformational changes in DNA
      molecule due to its complexation with oxaliplatin and duplex attains an
      intermediate conformational state having characteristics of both B- and C-form.
      Further, moderate binding strength of 4.12+/-0.2 * 104 M-1 for the interaction
      has been estimated via ultraviolet-visible spectroscopy. The inferences obtained
      from these investigations are encouraging and can form the basis for further
      exploration in the field of rational drug development based on platinum compounds
      possessing preferential binding for nucleic acid with improved competence.

PMID- 30282524
TI  - Immunopathogenesis of Acute Kidney Injury.
AB  - Pathophysiologically, the classification of acute kidney injury (AKI) can be
      divided into three categories: (1) prerenal, (2) intrinsic, and (3) postrenal.
      Emerging evidence supports the involvement of renal tubular epithelial cells and
      the innate and adaptive arms of the immune system in the pathogenesis of
      intrinsic AKI. Pro-inflammatory damage-associated molecular patterns, pathogen
      associated molecular patterns, hypoxia inducible factors, toll-like receptors,
      complement system, oxidative stress, adhesion molecules, cell death, resident
      renal dendritic cells, neutrophils, T and B lymphocytes, macrophages, natural
      killer T cells, cytokines, and secreted chemokines contribute to the
      immunopathogenesis of AKI. However, other immune cells and pathways such as M2
      macrophages, regulatory T cells, progranulin, and autophagy exhibit anti
      inflammatory properties and facilitate kidney tissue repair after AKI. Thus,
      therapies for AKI include agents such as anti-inflammatory (e.g., recombinant
      alkaline phosphatase), antioxidants (iron chelators), and apoptosis inhibitors.
      In preclinical toxicity studies, drug-induced kidney injury can be seen after
      exposure to a nephrotoxicant test article due to immune mechanisms and
      dysregulation of innate, and/or adaptive cellular immunity. The focus of this
      review will be on intrinsic AKI, as it relates to the immune and renal systems
      cross talks focusing on the cellular and pathophysiologic mechanisms of AKI.

PMID- 30282525
TI  - Decay of internal reference information in duration discrimination: Intertrial
      interval modulates the Type B effect.
AB  - Psychophysical evidence suggests that human perception of a stimulus is
      assimilated towards previous stimuli. The internal reference model (IRM) explains
      such assimilation through an internal reference (IR), which integrates past and
      present stimulus representations and thus might be conceived as a form of
      perceptual memory. In this study, we investigated whether the IR decays with
      time, as previously shown for perceptual memory representations in general. One
      specific prediction of IRM is higher discrimination sensitivity when a constant
      standard precedes rather than follows a variable comparison in a two-alternative
      forced-choice (2AFC) discrimination task. Furthermore, the magnitude of this so
      called negative Type B effect should decrease with decreasing weighting of past
      stimulus information in the integration process. Therefore, decay of the IR
      should result in a reduced Type B effect. To examine this prediction, we carried
      out a 2AFC duration discrimination experiment with a short (1,600 ms) and a long
      (3,200 ms) intertrial interval (ITI). As expected, a reduced negative Type B
      effect was observed at the long compared with the short ITI, consistent with the
      idea that humans rely on the immediate past when evaluating current sensory
      input, however, less so when the IR incorporating the perceptual short-term
      memory representation of these past stimuli has already decayed.

PMID- 30282526
TI  - The ability to recognise emotions predicts the time-course of sarcasm processing:
      Evidence from eye movements.
AB  - A core feature of sarcasm is that there is a discrepancy between the literal
      meaning of the utterance and the context in which it is presented. This means
      that a sarcastic statement embedded in a story introduces a break in local
      coherence. Previous studies have shown that sarcastic statements in written
      stories often elicit longer processing times than their literal counterparts,
      possibly reflecting the difficulty of integrating the statement into the story's
      context. In the present study, we examined how sarcastic statements are processed
      when the location of the local coherence break is manipulated by presenting the
      sarcastic dialogues either before or after contextual information. In total, 60
      participants read short text paragraphs containing sarcastic or literal target
      statements, while their eye movements were recorded. Individual differences in
      ability to recognise emotions and working memory capacity were measured. The
      results suggest that longer reading times with sarcastic statements not only
      reflect local inconsistency but also attempt to resolve the meaning of the
      sarcastic statement. The ability to recognise emotions was reflected in eye
      movement patterns, suggesting that readers who are poor at recognising emotions
      are slower at categorising the statement as sarcastic. Thus, they need more
      processing effort to resolve the sarcastic meaning.

PMID- 30282527
TI  - Different Vascular Responses to a Bare Nitinol Stent in Porcine Femoral and
      Femoropopliteal Arteries.
AB  - Nitinol stents are widely used for the treatment of peripheral arterial diseases
      in lower extremity arteries and have shown different clinical outcomes depending
      on implanted arterial segments. We aimed to compare histopathological responses
      to nitinol stents in femoral artery (FA) with those in femoropopliteal artery
      (FPA), which is markedly bended during knee flexion. A single nitinol stent was
      implanted in FA and FPA of 21 domestic swine. The stented vessels were
      angiographically assessed and then harvested for histopathology at 1 and 3 months
      after implantation. Angiographic late lumen loss was significantly greater in FPA
      than in FA at 3 months. Neointimal area decreased in FA and increased in FPA from
      1 to 3 months. Compared with FA, peri-strut area of FPA showed more pronounced
      hemorrhage and fibrin deposition at 1 month and angiogenesis and inflammation at
      1 and 3 months. Injury to internal elastic lamina or media was minimal in both FA
      and FPA at both time points. In conclusion, vascular responses to nitinol stents
      were different between FA and FPA with respect to time course of neointimal
      formation and progress of healing, suggesting that repetitive interaction between
      stent and vessel wall during dynamic vessel motion affected vascular responses.

PMID- 30282528
TI  - Exercise, diet, and the reinforcing value of food in an animal model of anorexia
      nervosa.
AB  - Activity-based anorexia (ABA) develops when laboratory rats are subjected to a
      single meal per day and have access to an activity wheel for the remaining time.
      Here, we studied the contribution of exercise and diet to the reinforcing value
      of food during ABA development. Three groups of eight adult male Wistar rats were
      used: an ABA group with 21.5 hr (then 22 hr) of wheel access and 1 hr (then 30
      min) of food access, a control group with the same time exposure to food but
      without exercise, and a yoked group to the ABA in terms of weight loss. Rats were
      daily tested on a progressive-ratio schedule to measure their motivation for
      food. ABA rats gradually reduced their body weight more than the food control
      group. Animals steadily increased their breaking points in parallel to losses in
      body weight, but no significant differences were found between groups. Adult rats
      can develop ABA, but their loss in weight neither resulted in a decrease of food
      intake nor in the motivation to obtain it.

PMID- 30282529
TI  - Top-down attentional factors modulate action priming in reach-to-grasp action.
AB  - Previous studies report that viewing exaggerated, high-lifting reaches (versus
      direct reaches) primes higher vertical deviation in wrist trajectory in the
      observer's subsequent reaches (trajectory priming), but it is unclear to what
      extent this effect depends upon task instructions relevant to top-down attention.
      In two experiments, participants were instructed to gaze at a dot presented on a
      large monitor for a colour-change go signal that cued them to execute a direct
      reach to a target. In the background, the monitor also displayed life-sized films
      of a human model. The films were of the model either remaining still or reaching
      to grasp a target with either a direct trajectory or an exaggerated, high-lifting
      trajectory. When the dot traced the human model's wrist throughout her movement,
      a robust trajectory priming effect emerged. When the dot remained stationary in a
      central location but the human model reached in the background, the human model's
      trajectory did not alter the participants' trajectories. Finally, when the dot
      traced exaggerated and direct trajectories and the human model remained
      stationary, the dot's movement produced an attenuated, non-significant trajectory
      priming effect. These findings show that top-down attentional factors modulate
      trajectory priming. In addition, a moving non-human stimulus does not produce the
      same degree of action priming when contextual factors make salient its
      independence of human agency and/or intention.

PMID- 30282530
TI  - Proceedings of the 2018 National Toxicology Program Satellite Symposium.
AB  - The 2018 annual National Toxicology Program Satellite Symposium, entitled
      "Pathology Potpourri," was held in Indianapolis, Indiana, at the Society of
      Toxicologic Pathology's 37th annual meeting. The goal of this symposium was to
      present and discuss challenging diagnostic pathology and/or nomenclature issues.
      This article presents summaries of the speakers' talks along with select images
      that were used by the audience for voting and discussion. Various lesions and
      other topics covered during the symposium included seminiferous tubule dysgenesis
      in rats, ameloblast and odontoblast degeneration/necrosis in a Sprague Dawley
      rat, intestinal leiomyositis in a beagle dog, gallbladder mucinous hyperplasia,
      focus of hepatocellular alteration and bile duct alteration in otters, renal
      tubule cytoplasmic vacuolation with basophilic granules in mice treated swith
      antisense oligonucleotide therapy, a uterine choriocarcinoma in a rhesus macaque,
      and rete ovarii proliferative ovarian lesions in various aged rat strains. One
      particularly provocative lesion was a malignant neoplastic proliferation in the
      renal pelvic region of a cynomolgus macaque from a 21-day study. Additional
      challenging lesions included thyroid proliferative lesions in zebra fish and
      gross findings in fish larvae during routine chemical screening. The Rabbit and
      Minipig International Harmonization of Nomenclature and Diagnostic Criteria Organ
      Working Groups also presented a series of challenging lesions.

PMID- 30282531
TI  - Endovascular treatment of proximal para-anastomotic aneurysms after previous
      surgical repair of infrarenal aortic aneurysms by the chimney technique.
AB  - Objectives To evaluate the use of chimney grafts in the treatment of para
      anastomotic aneurysms after previous abdominal aortic aneurysms open repair with
      short neck. Methods A retrospective analysis of prospectively collected data of
      consecutive patients who underwent endovascular repair for proximal aortic para
      anastomotic aneurysms following previous open repair for infrarenal abdominal
      aortic aneurysms was performed. All included patients had a short infrarenal
      aortic neck (<10 mm) excluding standard endovascular aortic repair. Five patients
      were symptomatic at the admission needed urgent treatment. Results Twelve
      patients with para-anastomotic aneurysms underwent placement of chimney grafts.
      The median time between the original operations to redo endovascular procedure
      was 11 years (interquartile range, 9.5 years). The mean infrarenal length was 4.3
      mm (1-9 mm). A total of 28 chimneys grafts were deployed for the 12 patients. The
      technical success rate was 91.7%. At a median radiologic follow-up of 16 months
      (2.0-29.4, 95% confidence interval), one patient died, while two late endoleaks
      and two reinterventions at one and three years for type Ia endoleak were
      performed by proximal extension and triple chimney graft placement. Conclusion
      The results of the present study show that ch-endovascular aortic repair is a
      safe technique for patients who suffered from proximal para-anastomotic aneurysms
      and having short neck unsuitable for standard endovascular repair. Longer follow
      up warranted to evaluate the durability of ch-endovascular aortic repair for this
      specific indication.

PMID- 30282532
TI  - Triangular Fibrocartilage Complex Repair and Ulna Variance: A Systematic Review.
AB  - BACKGROUND: This purpose of the study was to conduct a systematic review of
      available literature regarding the association between ulnar variance and
      outcomes after repair of peripheral traumatic tears of the triangular
      fibrocartilage complex (TFCC). METHODS: A systematic literature search of the
      medical literature about peripheral tears of the TFCC was performed. We selected
      seven studies comparing clinical outcome and ulnar variance in patients with
      peripheral TFCC tears. We evaluated quality of the articles using both the
      Structured Effectiveness Quality Evaluation Scale (SEQES) and Sackett's Level of
      Evidence (LOE). The outcomes were objective or self-assessment scoring systems
      for the function of the hand, wrist, or upper extremity. RESULTS: Seven articles
      were evaluated. The SEQES scores varied from 19 to 28, with a mean of 23. Five
      studies reported no association between ulnar variance and clinical outcome, and
      2 studies reported an association. The studies reporting no association either
      excluded or did not mention the cases of unstable distal radioulnar joint (DRUJ).
      CONCLUSIONS: This systematic review did not demonstrate strong evidence regarding
      the association between ulnar variance and outcomes after TFCC repair. As most of
      the studies did not distinguish between capsular and foveal tears which can
      affect DRUJ stability, further studies looking at this point are necessary to
      determine whether ulnar shortening osteotomy has an added value for better
      outcomes after TFCC repair.

PMID- 30282533
TI  - Continuous Peripheral Nerve Blocks for Early Active Mobilization after Hand
      Surgery: Four Case Reports.
AB  - Early active mobilization after hand surgery is extremely important for
      preventing scar tissue and adhesion. We examined four patients for whom
      continuous peripheral nerve blocks (CPNB) were used during and after hand
      surgery. This method was used for three median nerves and one ulnar nerve. A 2-cm
      incision was made at distal one-third of the forearm with local analgesia. The
      catheter tip was placed in the distal one-fourth of the forearm, and the hand
      surgery was begun. Early active mobilization and the self-rehabilitation exercise
      started immediately after the operation. The VAS scores during exercise were 0-2
      (mean: 1.3); pain was controlled sufficiently. Regarding ROM, excellent results
      were obtained for tenolysis, with good results for arthrolysis. No infection or
      postoperative nerve compression was found. This method, using CPNB with a
      portable infusion pump, is effective and safe for use at home for postoperative
      pain control.

PMID- 30282534
TI  - Novel Unidirectional Porous beta-Tricalcium Phosphate Used as a Bone Substitute
      after Excision of Benign Bone Tumors of the Hand: A Case Series.
AB  - Unidirectional porous beta-tricalcium phosphate (UDPTCP; Affinos(r), Kuraray,
      Tokyo, Japan) has been in clinical use since 2015. Animal studies have confirmed
      the excellent potential of UDPTCP with regard to bone formation and material
      absorption. We present the first three clinical cases using UDPTCP as a bone
      substitute after curettage of benign bone tumors of the hand. All three patients
      were males, 29-, 30- and 81-years-old, two having a diagnosis of enchondroma and
      the other, a bone ganglion, with a pathological fracture identified in one case.
      Over a mean follow-up of 10 months, all patients achieved satisfactory clinical
      result, with no adverse events of UDPTCP noted. Radiographic evidence of good
      bone formation and material absorption was observable over the postoperative
      course. UDPTCP provided satisfactory clinical results, with good biocompatibility
      and fast resorption characteristics. Therefore, UDPTCP could provide a safe and
      reliable filling substitute for bone defects following curettage of small bone
      tumors.

PMID- 30282535
TI  - Ulnar Subluxation of the Extensor Pollicis Longus Tendon as a Cause of Congenital
      Clasped Thumb: A Case Report.
AB  - A 15-year-old male patient presented with difficulty extending his right thumb
      due to subluxation of the extensor pollicis longus (EPL) tendon. Physical
      examination showed that active motion of the thumb's metacarpophalangeal (MP)
      joint was 76 degrees  in flexion and -58 degrees  in extension. During active
      extension, the EPL tendon shifted onto the ulnar aspect of the MP joint, and the
      extensor pollicis brevis (EPB) tendon shifted onto the central dorsal course of
      the MP joint. After repositioning by adducting the thumb into the palm to extend
      the MP joint (dynamic tenodesis effect), active extension of the MP joint
      increased to -12 degrees . Corrective surgery was performed under local
      anesthesia and radial sensory nerve block. Following plication of the attenuated
      dorsal capsule and sagittal band between the EPB and EPL, we confirmed that the
      patient could flex and extend the thumb smoothly. One year postoperatively, the
      extension deficit of the MP joint had not recurred.

PMID- 30282536
TI  - A Well-Differentiated Liposarcoma in the Digit: A Case Report of the 5-Year Post
      Surgical Follow-Up.
AB  - A liposarcoma is extremely rare in the digits. A 73-year-old woman was diagnosed
      with a lipoma in her middle finger 10 years ago. As this tumor increased in size
      and presented with imaging findings that were atypical of lipomas, careful
      marginal resection biopsy outside the pseudo-capsule was performed, and the tumor
      was diagnosed as a well-differentiated liposarcoma. At the 5-year follow-up, the
      patient showed no evidence of local recurrence or metastasis, with no loss of
      hand function. The findings from this case suggest that even for a lipomatous
      tumor in the digits, further imaging examination and resection biopsy should be
      considered if the tumor presents with features that are atypical of lipomas.

PMID- 30282537
TI  - Dorsal Capsular Defect and Synovial Fistula to the Fourth Extensor Compartment: A
      Late Complication after Arthroscopic Dorsal Wrist Ganglionectomy.
AB  - Arthroscopic dorsal wrist ganglionectomy is demonstrably a safe procedure with
      recurrence rates comparable to open surgery. We present a patient with wrist pain
      following arthroscopic ganglion excision. MRI and arthroscopic findings showed a
      large dorsal capsular defect, synovial fistula to the fourth extensor
      compartment, and dorsal radiocarpal ligament resection. Ligament reconstruction
      and capsular imbrication resolved her symptoms. We postulate that this
      complication resulted from a large capsular resection. Because we feel that it
      can be difficult to judge the size of the debridement through an arthroscope, the
      need for adequate capsular resection in dorsal wrist ganglionectomy needs to be
      balanced by consideration of potential complications from more aggressive
      capsular debridement, and thus we feel that capsular resection should be limited
      to no more than 1 cm2.

PMID- 30282538
TI  - The Effect of Distal Phalanx Bony Dimensions in Suture Anchor Fixations of Tendon
      Avulsion.
AB  - BACKGROUND: The terminal phalanx of the fingers carries the attachment of the
      Flexor Digitorum Profundus (FDP) on the volar surface and the extensor on the
      dorsal surface. Avulsion of these tendons has traditionally been repaired with
      pull-through sutures. Recently, bone anchor sutures have been found to be of
      comparable biomechanical strength but with the added advantage of technical ease
      and fewer complications. However, the dimensions of the bone, at the site of
      insertion of the anchors, have never been studied. METHODS: Following some cases
      of penetration of the dorsal cortex by the anchors, we measured the antero
      posterior dimensions of the terminal phalanx in 251 digits from plain radiographs
      and compared these with the dimensions of the commonly used bone anchors. We also
      compared male and female digits. RESULTS: The anchors were oversized in 76% of
      index, 78% of ring and 100% of little fingers in the female population and in
      49%, 44% and 97% of index, ring and little fingers respectively in the male
      population. CONCLUSIONS: This analysis of bone dimensions can be a useful guide
      to surgeons in choosing the appropriate implant for flexor tendon avulsions.

PMID- 30282539
TI  - Axial Rotation Test for Trapeziometacarpal Joint Hypermobility in the Normal
      Population.
AB  - BACKGROUND: The objective was to quantify joint laxity in healthy volunteers by
      measuring the passive axial rotation of the trapeziometacarpal joint using the
      axial rotation test. METHODS: Eighty volunteers (34 men and 46 women) were
      subjected to the axial rotation shear test and the degree of total rotational
      motion (TRM) was assessed. Volunteers were divided into Group I with a range of
      18-50 years old and Group II for 51 years and older. Statistical analysis was
      performed. RESULTS: The average TRM in Group I was 32.3 mm for women, and 27.4
      mm, for men (p = 0.04). The average TRM in women of Groups I and II, was 32.3 and
      21.6 mm respectively, (p < 0.001). The average TRM in men of Groups I and II, was
      27.4 and 19.4 mm (p < 0.001). In Group II the average TRM of women was 21.6 mm,
      and for men was 19.4 mm, which was not significantly different. CONCLUSIONS:
      Young women have greater degree of rotational laxity in the TM joint compared to
      men of the same age group and to older women. The axial rotation test can
      quantify the degree of rotational laxity of the TM joint.

PMID- 30282540
TI  - Establishing an Efficient Care Paradigm for Trigger Finger.
AB  - BACKGROUND: To identify the time course for efficacy of corticosteroid injections
      in the treatment of trigger finger. METHODS: A prospective single-center
      observational study was conducted, consisting of 38 patients with 41 trigger
      digits that were injected. Enrolled patients completed an initial Disabilities of
      the Arm, Shoulder, and Hand (DASH) questionnaire to determine the severity of
      their symptoms. Following the injection, patients were contacted at scheduled
      time points for up to 12 weeks to determine if, and when, objective resolution of
      symptoms occurred. Patients who received additional treatment, such as a second
      injection or surgery, and those who did not have objective relief of symptoms by
      12 weeks were classified as failed. Upon symptom resolution or injection failure,
      patients were given a DASH exit questionnaire. RESULTS: 30 of 41 injected trigger
      digits resolved and 11 failed treatment with a single corticosteroid injection.
      The latest that any study participant experienced resolution of symptoms was 69
      days. At 38 days, the rate of resolution of the study population slowed
      significantly. CONCLUSIONS: Although symptomatic resolution of trigger finger
      from a single corticosteroid injection can occur early on, a follow-up of 4 weeks
      (28 days) does not allow enough time for symptom resolution. The earliest a
      surgeon and patient should consider a secondary treatment is at 38 days. After 69
      days without resolution, both surgeon and patient can be confident that further
      treatment is needed.

PMID- 30282541
TI  - The Austrian Flag - Severe Carpal Tunnel Syndrome: A Case Report.
AB  - In severe carpal tunnel syndrome a continuum of neural changes takes place
      depending on the degree and duration of the compression, beginning with breakdown
      of the blood-nerve barrier, followed by endoneurial oedema and, subsequently,
      perineurial thickening and ischemia. Persisting chronic compression will
      eventually result in axonal degeneration. We report a case of longstanding carpal
      tunnel syndrome with amyloid deposits and the unusual intraoperative 'Austrian
      flag' sign.

PMID- 30282542
TI  - Is Pseudomeningocele an Absolute Sign of Root Avulsion Brachial Plexus Injury?
AB  - BACKGROUND: The finding of pseudomeningocele from cervical myelogram is widely
      accepted as a pathognomonic sign for diagnosing root avulsion in brachial plexus
      injury. In general, motor power in this setting should be absent. However, in
      clinical practice, we observed that motor power in some patients was still
      preserved. The objective of this study is to evaluate the accuracy of
      pseudomeningocele from cervical myelogram for predicting root avulsion in
      brachial plexus injury. METHODS: We retrospectively reviewed 201 patients with
      brachial plexus injury from 2007-2011. Four patients were excluded due to open
      wound injury. Motor power of the key muscle of each nerve root was evaluated by
      skilled hand surgeons. All cervical myelogram was interpreted by radiologists.
      Sensitivities, specificities, positive predictive values and negative predictive
      values were calculated with 95% confidence interval. RESULTS: Thirty and 29% of
      pseudomeningocele occurred at C7 and C8 level, respectively. The sensitivity of
      pseudomeningocele of each root from C5 to T1 was low (range, 10-62%). The
      specificity was high only at C5 (91%) and T1 (96.2%). Over 20% of patients with
      pseudomeningocele at C6-8 levels had some motor function. The initial muscle
      power of these patients was M1 or M2 and 70% of them recovered to at least M3 at
      the final follow-up. CONCLUSIONS: Pseudomeningocele is not an absolute sign for
      diagnosing of root avulsion in brachial plexus injury due to its high false
      positive rate when compared with preoperative motor function of each root.
      Careful examination of the key muscle of each root is extremely crucial to
      prevent unnecessary operation on that cervical nerve root.

PMID- 30282544
TI  - Motec Wrist Arthroplasty: 4 Years of Promising Results.
AB  - BACKGROUND: The Motec cementless modular metal-on-metal ball-and-socket wrist
      arthroplasty is an implant with promising intermediate results. An alternative to
      primary wrist fusion, total wrist arthroplasty is an option for active patients,
      who wish to retain their wrist function. It is indicated in cases of degenerative
      osteoarthritis, post-traumatic arthritis and rheumatoid (inflammatory) arthritis.
      METHODS: A prospective review of patient demographics, pre and post-operative
      Disabilities of the Arm Shoulder and Hand (DASH), MAYO scores, range of movements
      and grip strengths. All complications in follow up were recorded across the 4
      year period. RESULTS: 25 implants on 23 patients over 5.5 years, mean age 61; 8
      females and 15 male. 10 patients with SLAC, 3 SNAC, 5 inflammatory and 7 patients
      with generalized osteoarthritis. The patients showed significant improvements of
      MAYO and DASH scores post-operatively, as well as the flexion/extension arc and
      grip strengths. There was just one case of implant loosening- the radial screw
      after a wound infection, which was revised with a longer screw. Two implants were
      converted to Motec fusion due to pain. One implant was dislocated and relocated.
      The remaining patients have had good wrist function. Only 6 patients were unable
      to return to work. CONCLUSIONS: Similar to published studies, this series shows
      the Motec implant to be a good motion preserving alternative to total wrist
      fusion.

PMID- 30282543
TI  - Vacuum-Assisted Closure (VAC) Using Multiple Foam Pieces for Hidden Space
      Drainage through Less Exposure in Musculoskeletal Infections.
AB  - BACKGROUND: Purulent musculoskeletal infections often require surgical
      debridement and drainage. However, when the infection is extensive or involving
      multiple layers of tissues, maintaining drainage of the involved spaces can be
      difficult, even with the application of vacuum-assisted closure (VAC) therapy.
      Wide exposure and aggressive debridement is often required for such cases, which
      in turn may complicate wound coverage. METHODS: A retrospective review was
      performed for 16 patients with musculoskeletal infections treated surgically. The
      diagnosis for the patients consisted of necrotizing fasciitis, large soft tissue
      abscess, peri-hardware abscess, infected compartment syndrome, emphysematous
      osteomyelitis, and gas gangrene of diabetic foot. We minimized the incision and
      resection for debridement and drainage, and instead we placed multiple foam
      pieces between the tissues involved with VAC, to maintain drainage of the hidden
      spaces with negative pressure. RESULTS: Infection was successfully controlled in
      all cases. The mean duration of VAC treatment was 16.1 days (range, 5-36) and the
      mean number of VAC changes was 5.1 (range, 1-13). Primary wound closure was
      achieved in 11 cases, while skin grafts were used to cover the remaining five
      cases, which consisted of necrotizing fasciitis, infected compartment syndrome,
      and diabetic foot gas gangrene. No complications specifically associated with VAC
      therapy were observed. CONCLUSIONS: VAC using multiple foam pieces for hidden
      space drainage appears to be effective for infection control. It is helpful for
      minimizing exposure and resection for drainage and debridement, although
      subsequent reduction of the necessity or the level of wound coverage should
      further be investigated.

PMID- 30282546
TI  - Forearm Compartment Syndrome Concomitant with Pseudoaneurysm of the Anterior
      Interosseous Artery after Minor Penetrating Injury.
AB  - A 16-year-old man sustained a minor penetrating injury to his forearm, resulting
      in pseudoaneurysm formation that caused acute compartment syndrome with muscle
      contracture. Surgical treatment, including fasciotomy, evacuation of the hematoma
      and aneurysmectomy, followed by intensive hand therapy provided a successful
      outcome. Traumatic pseudoaneurysm after penetrating injury is a rare cause of
      acute forearm compartment syndrome. Although minor penetrating injuries tend to
      be underestimated, this type of injury can cause subsequent serious pathological
      conditions.

PMID- 30282545
TI  - Fixed Anterior Position of Ulnar Nerve around Medial Condyle of Elbow with Bony
      Mass Causing Cubital Tunnel Syndrome.
AB  - A 20-year-old male has presented with mild numbness and tingling sensation at 4,
      5th finger of his left hand. Simple radiograph and MRI images revealed bony mass
      at medial joint space of ulno-humeral joint. After surgical exploration, we found
      that there were two cause of ulnar nerve irritation symptom. Fixed ulnar nerve
      position at anterior aspect to medial condyle with deficiency of nerve gliding
      was one cause, and friction irritation around bony mass was another. It is rarely
      reported that ulnar nerve always travels to the anterior side of the medial
      condyle of the elbow, and there are no cases involving skeletal variation. In
      this case, the ulnar nerve may be penetrated while forming an anterior medial
      portal around elbow joint. It is important to know the path of the ulnar nerves
      very carefully through imaging and physical examination when there is a bony
      variant in the elbow joint.

PMID- 30282547
TI  - Collagenase Clostridium Histolyticum Injection with Precise Needle Length
      Adjusted by Silicone Tube Interposition for Dupuytren Contracture.
AB  - We describe our injection method for Collagenase Clostridium Histolyticum using a
      medical silicone tube after determining the optimal depth by ultrasonography.
      This procedure adjusts the exposed needle length to the planned injection depth
      by placing a sterilized silicone tube over the needle. The restricted depth
      provides not only precise injection into the middle of the cords but also avoids
      needle tip migration through the cord and into the vital structures, which
      prevents possible complications. This method is safe and simple.

PMID- 30282548
TI  - Repair Technique Using a Combination of Suture Anchor and Miniscrew in Flexor
      Digitorum Profundus Bony Avulsion Fracture with Bone Fragment in Zone 1.
AB  - Avulsion fracture of the volar base of the distal phalanx is a rare injury. Zone
      1 flexor tendon injuries can be treated with either internal or external fixation
      techniques. Pull-out suture repairs are often used for FDP tendon avulsion
      injuries. However, the pull out suture technique is associated with a number of
      well documented complications including nail bed injury and pressure necrosis.
      Despite the variety of techniques available for the repair of acute distal zone 1
      flexor tendon injuries, no one technique has proven to be superior to all others.
      We address our experience with treatment of FDP avulsion injuries using suture
      anchor and miniscrew. Our technique supplements the suture anchor technique,
      which often causes a lack of strength, with an additional miniscrew. We introduce
      two cases of combined method using both suture anchor and miniscrew for treatment
      of FDP avulsion injuries.

PMID- 30282549
TI  - Venous Thromboembolism in Upper Extremity Fractures.
AB  - BACKGROUND: Venous thromboembolism (VTE) has been studied in lower extremity
      fractures but little is known of its relation with upper extremity (UE)
      fractures. As an often overlooked but serious complication, VTE may compromise
      patient outcomes. METHODS: Using data on inpatients (aged >= 18 years) at a level
      I trauma center and patients in the National Surgical Quality Improvement Program
      database who sustained UE fractures (clavicle, humerus, or radius/ulna) and VTE
      in the same hospitalization between 2007 and 2014, the authors analyzed data on
      demographic characteristics, fracture type, VTE location (pulmonary embolism,
      lower extremity, or UE), VTE onset, polytrauma, operative or nonoperative
      management, comorbidities, and mortality. RESULTS: Of 1984 inpatients with UE
      fractures at 1 instution, 9 experienced VTE on admission, and 17 (15 received
      thromboprophylaxis) experienced VTE during hospitalization, for an overall VTE
      rate of 1.3%. VTE occurred most often in patients with fractures of the proximal
      humerus (3.0%) followed by the clavicle (2.0%), midshaft humerus (1.9%), distal
      radius/ulna (0.95%), and distal humerus/elbow (0.36%) (p = 0.0035). There were no
      significant trends in the incidence of PE (p = 0.33) over the study period, but
      there was a sharp rise since 2011. In the national database, 42 of 11570 (0.36%)
      patients with UE fracture had VTE, with incidence by fracture location ranging
      from 0.14% (radius/ulna) to 0.98% (proximal humerus) (p = 0.00001). Predictors
      were chronic steroid use (odds ratio [OR] = 6.22, p = .030), inpatient status (OR
      = 4.09, p = .002), and totally disabled functional status (OR = 3.31, p = .021).
      CONCLUSIONS: VTE incidence was highest following proximal humerus or clavicle
      fractures and are rarely associated with radius/ulna fractures. There may have
      been a rise in the incidence of PE since 2007, warranting further investigation.

PMID- 30282550
TI  - Clinical Examination of the Extensor Pollicis Brevis: Anatomical Study and
      Description of a Novel Clinical Sign.
AB  - BACKGROUND: The Extensor Pollicis Brevis (EPB) is an extrinsic thumb muscle whose
      main function is extension of the first metacarpophalangeal joint (MCPJ). It is
      subject to significant anatomical variation and may be absent, vestigial or have
      an anomalous distal attachment. Clinical examination of EPB is notoriously
      difficult and no reliable test has yet been described. We propose a novel test
      for the accurate examination of EPB. We sought to clarify the anatomical
      variations of EPB and to validate our clinical test using human cadaveric
      anatomical tests. METHODS: A structured literature review of all human cadaveric
      anatomical studies describing the attachments of EPB was performed using MEDLINE
      and Embase with the key words "Extensor Pollicis Brevis". A cadaveric anatomical
      study was performed using 18 unembalmed upper limbs. Positive and negative tests
      were simulated by manipulating the tendons of EPB, Extensor Pollicis Longus (EPL)
      and Flexor Pollicis Longus (FPL). Changes in tendon tension and joint position
      were measured and recorded. The EPB anatomy was then determined by dissection.
      RESULTS: Anatomical variations were present in the majority of wrists, with only
      35% of EPB tendons having a distal attachment to the proximal phalanx alone. EPB
      was absent in 5% of specimens. There was a significant difference between the
      change in MCPJ position between a positive (36 degrees; 95% CI 25 to 47 degrees)
      and negative (19 degrees; 95% CI 14 to 25 degrees) clinical test (p = 0.002).
      CONCLUSIONS: The functional importance of EPB depends on its congenital
      architecture in addition to the functional demands of the patient. We report a
      novel clinical test which is effective in demonstrating the integrity of the EPB.
      A positive test result is observed when a change in MCPJ position that occurs
      while the interphalangeal joint is brought into flexion from full thumb extension
      is 25 degrees or more.

PMID- 30282551
TI  - Cost Comparison of Collagenase Clostridium Histolyticum and Fasciectomy for
      Treatment of Dupuytren's Contracture in the Australian Health System.
AB  - BACKGROUND: Dupuytren's disease results in contracted cords in the hand that lead
      to deformity and disability. Current treatment options include fasciectomy and an
      injectable, collagenase clostridium histolyticum. No cost comparison studies have
      been published within the Australian health care environment. METHODS: A
      retrospective review of all patients treated for Dupuytren's disease in a major
      teaching hospital was undertaken to compare the costs of treatment by fasciectomy
      or collagenase injection. RESULTS: Eighteen patients underwent fasciectomy and 21
      collagenase clostridium histolyticum injections were performed during the study
      period and were eligible for inclusion under the review criteria. Of the 39
      patients, 36 were male and 3 were female with an average age 66.4 years (50-85).
      Twenty-five digits were treated by fasciectomy in 18 patients, and 23 digits were
      treated by collagenase in 21 patients. The fasciectomy group attended an average
      9.2 visits (5-22), incurring an average costing of US$5738.12 per patient
      ($3181.18-$9618.10). The collagenase group attended an average 3.8 visits (3-8),
      incurring an average costing of US$2076.83 per patient ($1842.24-$3929.57).
      CONCLUSIONS: Collagenase treatment of Dupuytren's contracture represents a
      significant reduction in cost relative to fasciectomy, with 64% savings, length
      of follow up and number of visits. This is a similar finding to studies in other
      countries.

PMID- 30282552
TI  - Anatomical Basis for Arthroscopy of the Proximal Interphalangeal Joints.
AB  - BACKGROUND: Arthroscopy is a widely used minimally invasive technique.
      Nevertheless, no report describes the arthroscopic anatomy of the proximal
      interphalangeal (PIP) joint for portal creation. To facilitate arthroscopy, this
      study elucidated the anatomy of the lateral bands of the extensor mechanism and
      collateral ligaments of PIP joints. METHODS: A total of 39 fingers from the right
      hands of 10 cadavers (4 males, 6 females) were evaluated in this study. We
      defined the extension line from the proximal interphalangeal volar crease as the
      C-line. We also defined an imaginary line along the distal edge of the proximal
      phalanx, which is parallel to the C-line, as the J-line. The distance between J
      line and C-line was measured. On the C-line and J-line, we measured the
      following: from the dorsal skin to the lateral edge of the lateral band (LB), the
      dorsal edge of the collateral ligament (CL) and from the lateral band and the
      collateral ligament (D), the width of the finger (W). The finger half-width (M)
      was measured on the J-line. Comparison between the digits and comparison between
      radial and ulnar distance were measured and statistical analysis was performed.
      RESULTS: All PIP joint spaces were distal from the C-line, except for one ring
      finger. The average distances between the J-line and C-line were 1.8-3.2 mm. On
      the C-line, only 11 cases (14.1%) showed an interval between the lateral bands
      and the collateral ligaments, but, on the J-line 72, cases (92.3%) had such an
      interval. The interval was located 1.6-2.9 mm in a dorsal direction from the
      midlateral on the J-line. CONCLUSIONS: Portal creation at the J-line is safer
      than at the C-line. This study revealed that safe portals for arthroscopy of the
      PIP joint are 2 mm dorsal to the midlateral line of the finger on the J-line.

PMID- 30282553
TI  - Effects of the Elbow Flexion Angle on the Radial Nerve Location around the
      Humerus: A Cadaver Study for Safe Installation of a Hinged External Fixator.
AB  - BACKGROUND: This study aimed to investigate whether the distance between the
      radial nerve and rotational center of the elbow joint when observing from the
      lateral surface of the humerus changes according to passive elbow joint flexion
      for safe external fixation with a hinged fixator of the elbow joint. METHODS:
      Twenty fresh-frozen cadaveric arms were dissected. The points where the radial
      nerve crosses over the posterior aspect of the humerus, crosses through the
      lateral center, and crosses over the anterior aspect of the humerus were defined
      in the lateral view of the elbow joint, using fluoroscopy, as R1, R2, and R3,
      respectively. The distances between the rotational center and each point on the
      radial nerve were measured when the flexion angle of the elbow joint was 10
      degrees , 50 degrees , 90 degrees , and 130 degrees . RESULTS: The distances
      between the rotational center and R1, R2, and R3 were 118 mm, 94 mm, and 65 mm,
      respectively, when the flexion angle was 10 degrees ; 112 mm, 93 mm, and 74 mm,
      respectively, for 50 degrees ; 108 mm, 93 mm, and 77 mm, respectively, for 90
      degrees ; and 103 mm, 94 mm, and 83 mm, respectively, for 130 degrees . The
      distance between the rotational center and R2 was constant regardless of the
      flexion angle. With elbow joint extension, the distances between R1 and R3
      increased; the safe zone, a region where the radial nerve would not be located on
      the humerus, was the smallest in extension. When the elbow joint was flexed, the
      distances between R1 and R3 decreased; the safe zone was the largest in flexion.
      CONCLUSIONS: This study showed that the radial nerve location on the humerus
      varied based on the flexion angle of the elbow joint; the safe zone may change. A
      half-pin can be likely inserted safely, avoiding the elbow joint extension
      position.

PMID- 30282554
TI  - A Functional Angle of Up to 35 degrees  at the Distal Interphalangeal Joint Can
      Be Achieved with Headless Compression Screw Fusion.
AB  - BACKGROUND: Arthrodesis of the distal interphalangeal (DIP) joint reliably
      improves symptomatic arthritis. A range of successful surgical techniques
      including tension band wiring, plate fixation and headless compression screws
      have been described and produce stable painless unions. For best functional
      outcome, the fusion angle should be between 10 and 61 degrees. In the past, it
      has been difficult to achieve more than 10 degrees of flexion with a headless
      compression screw. Higher fusion angles have been reported using tension band
      wiring techniques. However, metalwork prominence is a common problem and may
      require revision surgery to rectify this. Headless compression screws are
      reported to cause iatrogenic fractures due to the size of the screw relative to
      the small diameter of the phalanx. This case series achieves an angle of up to 35
      degrees with a good functional outcome. METHODS: Open fusion of the DIP joint
      with a headless cannulated compression screw, of 2.2 mm in diameter, was
      undertaken in fifteen digits. Patients received standard departmental follow up
      to radiographic union. Patients self-reported function using the Michigan Hand
      Questionnaire post operatively. The fusion angles achieved were assessed on
      postoperative radiographs. RESULTS: All patients went on to a stable union
      without any patients requiring revision surgery as a result of fracture or
      protrusion of metalwork. Complications were observed in two patients which
      included one superficial infection (n = 1) and a discomfort requiring removal of
      metalwork (n = 1). Functional scores measured post operatively showed favourable
      outcomes. CONCLUSIONS: In this series, successful fusions of the DIP joints, at
      an angle up to 35 degrees were achieved using small diameter headless compression
      screws, which provided benefits including early mobilization and favourable
      functional outcome scores.

PMID- 30282555
TI  - Reliability and Concurrent Validity of the Ring Gauge Method and the Metacarpal
      Head Tape Measure Method of Measuring Hand Size.
AB  - BACKGROUND: There are several methods for measuring edema of the hand. While the
      volumetric techniques, finger circumference measurement, and figure-of-eight
      techniques have undergone extensive psychometric testing, alternative methods of
      measuring hand size, such as circumferential finger size determination using a
      ring gauge (ring gauge method; RGM) and tape measurement of hand girth taken
      along the distal palmar crease (metacarpal head tape measure method; MHTM), have
      not. This study's aim is to examine the reliability and validity of the RGM and
      the MHTM. METHODS: In this cross-sectional study, two examiners measured 22 hands
      in 22 patients with hand edema using the RGM and the MHTM 3 times each to
      determine intra- and inter-tester reliability. The validity of each method was
      established using the finger circumference measurement and figure-of-eight
      method, respectively. RESULTS: The intra-class correlation coefficient (ICC)
      obtained for intra-tester reliability was 0.99-0.98 for both methods. ICCs for
      inter-tester reliability were 0.97-0.98 for the RGM and 0.98 for the MHTM.
      Pearson product-moment correlation values between the RGM and finger
      circumference measurement were 0.92-0.96, while those between the MHTM and figure
      of-eight method were 0.84-0.90. CONCLUSIONS: The RGM and the MHTM are reliable
      and valid evaluation tools for the assessment of hand size.

PMID- 30282556
TI  - Midwest Nursing Research Society News.

PMID- 30282557
TI  - Neuroblastoma, opsoclonus-myoclonus ataxia syndrome and neonatal lupus with
      congenital heart block: is there an association?

PMID- 30282558
TI  - Pathogenic role of antiphospholipid antibodies: an update.

PMID- 30282559
TI  - Generalized anhidrosis as first clinical presentation of systemic lupus
      erythematosus.

PMID- 30282560
TI  - The anti-thrombotic effects of vitamin D and their possible relationship with
      antiphospholipid syndrome.
AB  - The importance of the immunomodulatory effects of vitamin D has recently been
      associated with autoimmune and chronic inflammatory diseases. Vitamin D
      deficiency has been linked to the development of autoimmune conditions.
      Antiphospholipid syndrome is an autoimmune disease characterized by thrombotic
      events and obstetric complications in patients with antiphospholipid antibodies.
      Current data show that patients with antiphospholipid syndrome have a high
      prevalence of vitamin D deficiency even without classic risk factors. Several
      studies have suggested vitamin D may have anti-thrombotic functions. In
      antiphospholipid syndrome, low vitamin D serum levels have been associated with
      thrombotic manifestations, suggesting a possible protective role of vitamin D in
      antiphospholipid syndrome. This literature review presents current evidence on
      the haemostatic functions of vitamin D and their possible relationship with the
      clinical manifestations of antiphospholipid syndrome.

PMID- 30282561
TI  - The blood-brain barrier, TWEAK, and neuropsychiatric involvement in human
      systemic lupus erythematosus and primary Sjogren's syndrome.
AB  - OBJECTIVE: A prevailing hypothesis for neuropsychiatric involvement in systemic
      lupus erythematosus (SLE) and primary Sjogren's syndrome is that brain reactive
      autoantibodies enter the brain through a disrupted blood-brain barrier. Our aim
      was to investigate whether TNF-like weak inducer of apoptosis (TWEAK) plays a
      role in cerebral involvement in human SLE and primary Sjogren's syndrome, and
      whether an impaired blood-brain barrier is a prerequisite for neuropsychiatric
      manifestations. METHODS: TWEAK was measured in the cerebrospinal fluid and serum
      and compared with markers of blood-brain barrier permeability (Q-albumin and MRI
      contrast-enhanced lesions) and S100B, an astrocyte activation marker in 50 SLE
      and 52 primary Sjogren's syndrome patients. Furthermore, we estimated the general
      intrathecal B-cell activation (IgG index), measured anti-NR2 antibodies in
      cerebrospinal fluid, and explored whether these variables were associated with
      neuropsychiatric manifestations. RESULTS: No associations were found between
      TWEAK in the cerebrospinal fluid or serum and neuropsychiatric manifestations in
      SLE nor in primary Sjogren's syndrome patients. Furthermore, no associations were
      found between neuropsychiatric manifestations and indicators of blood-brain
      barrier integrity or astroglial activity. Anti-NR2 antibodies were associated
      with impaired visuospatial processing (odds ratio 4.9, P = 0.03) and motor
      functioning (odds ratio 6.0, P = 0.006). CONCLUSION: No clinical neuropsychiatric
      manifestations could be attributed to impaired integrity of the blood-brain
      barrier, or to TWEAK levels in cerebrospinal fluid or serum in either patient
      group. The TWEAK concentration was considerably higher in the cerebrospinal fluid
      than in blood, which indicates intrathecal production. We hypothesize that
      increased TWEAK and S100B result from immunological stress caused by brain
      reactive antibodies produced by brain residing immune cells.

PMID- 30282562
TI  - Systemic lupus erythematosus is a risk factor for cardiovascular disease: a
      nationwide, population-based study in Korea.
AB  - OBJECTIVE: To investigate the incidence and clinical significance of
      cardiovascular disease in systemic lupus erythematosus patients. METHODS: We
      included systemic lupus erythematosus patients ( n = 18,575) without previous
      cardiovascular disease and age- and sex-matched individuals without systemic
      lupus erythematosus (controls; n = 92,875) from the Korean National Health
      Insurance Service database (2008-2014). Both cohorts were followed up for
      incident cardiovascular disease and death until 2015. RESULTS: During follow up,
      myocardial infarction occurred in 203 systemic lupus erythematosus patients and
      325 controls (incidence rate: 1.76 and 0.56 per 1000 person-years, respectively),
      stroke occurred in 289 patients and 403 controls (incidence rate: 2.51 and 0.70
      per 1000 person-years, respectively), heart failure occurred in 358 patients and
      354 controls (incidence rate 3.11 and 0.61 per 1000 person-years, respectively),
      and death occurred in 744 patients and 948 controls (incidence rate 6.54 and 1.64
      per 1000 person-years, respectively). Patients with systemic lupus erythematosus
      had higher risks for myocardial infarction (hazard ratio: 2.74, 95% confidence
      interval: 2.28-3.37), stroke (hazard ratio: 3.31, 95% confidence interval: 2.84
      3.86), heart failure (hazard ratio: 4.60, 95% confidence interval: 3.96-5.35),
      and cardiac death (hazard ratio: 3.98, 95% confidence interval: 3.61-4.39).
      CONCLUSIONS: Here, systemic lupus erythematosus was an independent risk factor
      for cardiovascular disease, thus cardiac assessment and management are critical
      in systemic lupus erythematosus patients.

PMID- 30282563
TI  - Stillbirth in Western Australia, 2005-2013: the influence of maternal migration
      and ethnic origin.
AB  - OBJECTIVE: To investigate prevalence rates and the risk of ante- and intrapartum
      stillbirth in Western Australia with respect to maternal country of birth and
      ethnic origin. DESIGN, SETTING AND PARTICIPANTS: Whole population retrospective
      cohort analysis of de-identified, linked routinely collected birth, perinatal and
      mortality data for all births to non-Indigenous women in WA during 2005-2013.
      MAIN OUTCOME MEASURES: Crude and adjusted odds ratios (aORs) with 95% confidence
      intervals were estimated by logistic regression and adjusted for confounding
      factors, for all stillbirths, antepartum stillbirths and intrapartum stillbirths,
      stratified by migrant status and ethnic background (white, Asian, Indian,
      African, Maori, other). RESULTS: Women born overseas were more likely to have a
      stillbirth than Australian-born women (aOR, 1.26; 95% CI, 1.09-1.37). There was
      no significant difference for any type of stillbirth between Australian-born
      women of white and non-white backgrounds, but non-white migrant women were more
      likely than white migrants to have a stillbirth (OR, 1.42; 95% CI, 1.19-1.70).
      Compared with Australian-born women, migrants of Indian (aOR, 1.71; 95% CI, 1.17
      2.47), African (aOR, 2.12; 95% CI, 1.46-3.08), and "other" ethnic origins (aOR,
      1.43; 95% CI, 1.06-1.93) were more likely to have antepartum stillbirths; women
      of African (aOR, 5.08; 95% CI, 3.14-8.22) and "other" (aOR, 1.86; 95% CI, 1.15
      3.00) background were more likely to have an intrapartum stillbirth. CONCLUSIONS:
      Immigrants of African or Indian background appear to be at greater risk of ante-
      and intrapartum stillbirth in WA. Specific strategies are needed reduce the
      prevalence of stillbirth in these communities.

PMID- 30282565
TI  - Mechanical circulatory support using modified TandemHeart ventricular assist
      device in neonates with CHD - CORRIGENDUM.

PMID- 30282564
TI  - Unintended and unwanted pregnancy in Australia: a cross-sectional, national
      random telephone survey of prevalence and outcomes.

PMID- 30282566
TI  - Whole-genome sequencing for methicillin-resistant Staphylococcus aureus (MRSA)
      outbreak investigation in a neonatal intensive care unit.
AB  - OBJECTIVE: To evaluate whole-genome sequencing (WGS) as a molecular typing tool
      for MRSA outbreak investigation. DESIGN: Investigation of MRSA
      colonization/infection in a neonatal intensive care unit (NICU) over 3 years
      (2014-2017). SETTING: Single-center level IV NICU.PatientsNICU infants and
      healthcare workers (HCWs). METHODS: Infants were screened for MRSA using a swab
      of the anterior nares, axilla, and groin, initially by targeted (ring) screening,
      and later by universal weekly screening. Clinical cultures were collected as
      indicated. HCWs were screened once using swabs of the anterior nares. MRSA
      isolates were typed using WGS with core-genome multilocus sequence typing
      (cgMLST) analysis and by pulsed-field gel electrophoresis (PFGE). Colonized and
      infected infants and HCWs were decolonized. Control strategies included
      reinforcement of hand hygiene, use of contact precautions, cohorting, enhanced
      environmental cleaning, and remodeling of the NICU. RESULTS: We identified 64
      MRSA-positive infants: 53 (83%) by screening and 11 (17%) by clinical cultures.
      Of 85 screened HCWs, 5 (6%) were MRSA positive. WGS of MRSA isolates identified 2
      large clusters (WGS groups 1 and 2), 1 small cluster (WGS group 3), and 8
      unrelated isolates. PFGE failed to distinguish WGS group 2 and 3 isolates. WGS
      groups 1 and 2 were codistributed over time. HCW MRSA isolates were primarily in
      WGS group 1. New infant MRSA cases declined after implementation of the control
      interventions. CONCLUSION: We identified 2 contemporaneous MRSA outbreaks
      alongside sporadic cases in a NICU. WGS was used to determine strain relatedness
      at a higher resolution than PFGE and was useful in guiding efforts to control
      MRSA transmission.

PMID- 30282567
TI  - Prevalence and predictors of malnutrition in elderly Chinese adults: results from
      the China Health and Retirement Longitudinal Study.
AB  - OBJECTIVE: China has the largest population of elderly citizens in the world,
      with 177 million adults aged 60 years or older. However, no national estimate of
      malnutrition in elderly Chinese adults exists. We estimated the prevalence and
      predictors of malnutrition in this population. DESIGN: Data from the second wave
      of the Chinese Health and Retirement Longitudinal Study (CHARLS) include
      interview and biomarker data for 6450 subjects aged 60 years or older from 448
      different communities in twenty-eight provinces, allowing for nationally
      representative results. Malnutrition was identified based on the ESPEN (European
      Society of Parenteral and Enteral Nutrition and Metabolism) criteria. We used
      multivariable regression to investigate the predictors of malnutrition, including
      demographic factors, marital status, self-reported health status, self-reported
      standard of living, health insurance status and education. SETTING: China.
      SUBJECTS: Community-dwelling Chinese adults aged 60 years or older. RESULTS: The
      prevalence of malnutrition in elderly Chinese adults was 12.6 %. Malnutrition was
      most common among those who were older (OR=1.09; 95 % CI 1.07, 1.10), male
      (OR=1.41; 95 % CI 1.10, 1.79), lived in rural areas (v. urban: OR=0.75; 95 % CI
      0.57, 1.00) or lacked health insurance (P<0.01). CONCLUSIONS: The burden of
      malnutrition on elderly Chinese adults is significant. Based on current
      population estimates, up to 20 million are malnourished. Malnutrition is strongly
      associated with demographic factors, shows a trend to association with health
      status and is not strongly associated with standard of living or education. A
      coordinated effort is needed to address malnutrition in this population.

PMID- 30282568
TI  - Automated Indices of Clustering and Switching of Semantic Verbal Fluency in
      Parkinson's Disease.
AB  - OBJECTIVES: Deficits in semantic verbal fluency (SVF) can stem from dysfunction
      of an executive control system and/or of semantic knowledge. Previous analyses of
      SVF responses were devised to characterize these two components including
      switching and mean cluster size (MCS) indices, but these rely on subjective
      experimenter-based assessment of the words' relatedness. To address this
      limitation, computational data-driven SVF indices have been developed. Our aim is
      to assess the validity and usefulness of these automated indices in the context
      of cognitive decline in Parkinson's disease (PD). METHODS: This is a
      retrospective study including 50 advanced PD patients with (n=28) or without
      (n=22) mild cognitive impairment (PD-MCI). We analyzed animal SVF outputs using
      an automated computational approach yielding switching, MCS, and cumulative
      relatedness (CuRel) indices. We compared these indices to the classic
      experimenter-based switching and MCS indices to assess concurrent validity, and
      against neuropsychological measures of executive functioning and semantic
      knowledge to assess construct validity. We also examined whether these indices
      were impaired and predicted PD-MCI. RESULTS: Automated switching indices, but not
      MCS or CuRel, showed evidence of concurrent and construct validity, and
      characterized individual difference in advanced PD. Automated switching indices
      also outperformed the experimenter-dependent index in predicting the presence of
      PD-MCI. CONCLUSION: Computational methods hold promise as fine-grained, unbiased
      indices reflecting the executive component of SVF, but none of the methods
      provided valid measures of semantic knowledge in PD. Our data also confirm that
      SVF are not adequate tests of semantic memory in patients with executive
      dysfunction such as PD. (JINS, 2018, 24, 1047-1056).

PMID- 30282569
TI  - Transdiagnostic dimensions of psychopathology at first episode psychosis:
      findings from the multinational EU-GEI study.
AB  - BACKGROUND: The value of the nosological distinction between non-affective and
      affective psychosis has frequently been challenged. We aimed to investigate the
      transdiagnostic dimensional structure and associated characteristics of
      psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic
      categories, we expected that positive symptoms occurred more frequently in ethnic
      minority groups and in more densely populated environments, and that negative
      symptoms were associated with indices of neurodevelopmental impairment. METHOD:
      This study included 2182 FEP individuals recruited across six countries, as part
      of the EUropean network of national schizophrenia networks studying Gene
      Environment Interactions (EU-GEI) study. Symptom ratings were analysed using
      multidimensional item response modelling in Mplus to estimate five theory-based
      models of psychosis. We used multiple regression models to examine demographic
      and context factors associated with symptom dimensions. RESULTS: A bifactor
      model, composed of one general factor and five specific dimensions of positive,
      negative, disorganization, manic and depressive symptoms, best-represented
      associations among ratings of psychotic symptoms. Positive symptoms were more
      common in ethnic minority groups. Urbanicity was associated with a higher score
      on the general factor. Men presented with more negative and less depressive
      symptoms than women. Early age-at-first-contact with psychiatric services was
      associated with higher scores on negative, disorganized, and manic symptom
      dimensions. CONCLUSIONS: Our results suggest that the bifactor model of
      psychopathology holds across diagnostic categories of non-affective and affective
      psychosis at FEP, and demographic and context determinants map onto general and
      specific symptom dimensions. These findings have implications for tailoring
      symptom-specific treatments and inform research into the mood-psychosis spectrum.

PMID- 30282571
TI  - Influence of follicle size on bovine oocyte lipid composition, follicular
      metabolic and stress markers, embryo development and blastocyst lipid content.
AB  - This study assessed the lipid composition of oocytes from different follicle
      sizes and compared the expression of lipid-related genes and follicular fluid
      (FF) molecules between groups. We also investigated the functional consequences
      of differences on embryo development and blastocyst lipid deposits. Oocytes and
      FF were recovered from different follicle sizes. Oocytes from small (<=5 mm) and
      large (>=6mm) bovine follicles were used to produce Day 7 expanded blastocysts
      (Day7Ex) and blastocysts that only became expanded at Day 8 (Day8Ex) after
      insemination. Oocytes from >8 mm follicles had the highest lipid content. Few
      oocyte phospholipid variations were identified between groups. Very long chain
      fatty acid elongase 6 (ELOVL6) mRNA abundance was reduced in larger follicle
      derived oocytes compared with the <=2mm group. Increased levels of glucose,
      reactive oxygen species, glutathione and superoxide dismutase activity were also
      identified in FF from larger follicles. Large follicle-derived embryo development
      and lipid content of Day7Ex were greater than those derived from small follicles.
      Day8Ex had greater lipid deposition than Day7Ex. Oocytes and blastocysts
      exhibited follicle size-specific lipids. Large-follicle oocytes had increased
      lipid content and became Day7Ex with greater lipid deposition whereas delayed
      blastocoel expansion associated with a prolonged period of culture determined the
      lipid accumulation of Day8Ex. The FF microenvironment of large follicles seems to
      favour embryo development.

PMID- 30282570
TI  - Comparison of Aerosol- and Percutaneous-acquired Venezuelan Equine Encephalitis
      in Humans and Nonhuman Primates for Suitability in Predicting Clinical Efficacy
      under the Animal Rule.
AB  - Licensure of medical countermeasure vaccines to protect against aerosolized
      Venezuelan equine encephalitis virus (VEEV) requires the use of the Animal Rule
      to assess vaccine efficacy, because human studies are not feasible or ethical. We
      therefore performed a retrospective study of VEE cases that occurred in at-risk
      laboratory workers and support personnel during the United States Biowarfare
      Program (1943-1969) to better define percutaneous- and aerosol-acquired VEE in
      humans and to compare these results with those described for the NHP model (in
      which high-dose aerosol VEEV challenge led to more severe encephalitis than
      parenteral challenge). Record review and analysis of 17 aerosol- and 23
      percutaneous-acquired human cases of VEE included incubation period, symptoms,
      physical examination findings, and markers of infection. Human VEE disease by
      both exposure routes presented as acute febrile illness, typically with fever,
      chills, headache, back pain, malaise, myalgia, anorexia, and nausea. Aerosol
      exposure more commonly led to upper respiratory tract-associated findings of sore
      throat (59% compared with 26%), pharyngeal erythema (76% compared with 52%), neck
      pain (29% compared with 4%), and cervical lymphadenopathy (29% compared with 4%).
      Other disease manifestations, including encephalitis, were similar between the 2
      exposure groups. The increase in upper respiratory tract findings in aerosol
      acquired VEE in humans has not previously been reported but is supported by the
      mouse model, which showed nasal mucosal necrosis, necrotizing rhinitis, and an
      increase in upper respiratory tract viral burden associated with aerosol VEEV
      challenge. Fever, viremia, and lymphopenia were common markers of VEE disease in
      both humans and NHP, regardless of the exposure route. Taken collectively, our
      findings provide support for use of the nonlethal NHP model for advanced
      development of medical countermeasures against aerosol- or percutaneous-acquired
      VEE.

PMID- 30282572
TI  - Effects of ten-eleven translocation 1 (Tet1) on DNA methylation and gene
      expression in chicken primordial germ cells.
AB  - Ten-eleven translocation 1 (Tet1) is involved in DNA demethylation in primordial
      germ cells (PGCs); however, the precise regulatory mechanism remains unclear. In
      the present study the dynamics of 5-methylcytosine (5mC) and 5
      hydroxymethylcytosine (5hmC) in developing PGCs and the role of Tet1 in PGC
      demethylation were analysed. Results show that 5mC levels dropped significantly
      after embryonic Day 4 (E4) and 5hmC levels increased reaching a peak at E5-E5.5.
      Interestingly, TET1 protein was highly expressed during E5 to E5.5, which showed
      a consistent trend with 5hmC. The expression of pluripotency-associated genes
      (Nanog, PouV and SRY-box 2 (Sox2)) and germ cell-specific genes (caveolin 1
      (Cav1), piwi-like RNA-mediated gene silencing 1 (Piwi1) and deleted in
      azoospermia-like (Dazl)) was upregulated after E5, whereas the expression of
      genes from the DNA methyltransferase family was decreased. Moreover, the Dazl
      gene was highly methylated in early PGCs and then gradually hypomethylated.
      Knockdown of Tet1 showed impaired survival and proliferation of PGCs, as well as
      increased 5mC levels and reduced 5hmC levels. Further analysis showed that
      knockdown of Tet1 led to elevated DNA methylation levels of Dazl and
      downregulated gene expression including Dazl. Thus, this study reveals the
      dynamic epigenetic reprogramming of chicken PGCs in vivo and the molecular
      mechanism of Tet1 in regulating genomic DNA demethylation and hypomethylation of
      Dazl during PGC development.

PMID- 30282574
TI  - Biased Results Owing to Competing Interests?

PMID- 30282573
TI  - Medical Treatment of COPD.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is common around the
      world and carries a high morbidity and mortality. Symptom- and risk-oriented drug
      treatment is recommended, both in Germany and in other countries. It is not yet
      known to what extent the treatment that is actually delivered in Germany
      corresponds to the current recommendations in the guidelines. METHODS: As
      recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      in 2017, 2281 patients of the national COPD cohort COSYCONET (COPD and Systemic
      Consequences-Comorbidities Network) were classified into Gold classes A-D on the
      basis of disease-specific manifestations and the frequency of exacerbations.
      Moreover, the regular use of medications was documented and categorized according
      to active substance groups. For all groups, the documented treatment that was
      actually given was compared to the recommended treatment. RESULTS: 67.6% of the
      patients received a combination of a long-acting anticholinergic drug (LAMA) and
      a long-acting beta-mimetic drug (LABA), while 65.8% received inhaled
      corticosteroids (ICS), 11.7% theophylline, and 12.6% oral corticosteroids (OCS).
      Despite recommendations to the contrary, 66% of the patients in Groups A and B
      (low exacerbation rates) were treated with ICS; some of these patients carried an
      additional diagnosis of bronchial asthma. There was evidence of undertreatment
      mainly in groups C and D (high exacerbation rate), because many of the patients
      in these groups were not treated with LAMA or LAMA/LABA as recommended.
      CONCLUSION: The observed deviations from the recommended treatment, some of which
      were substantial, might lead to suboptimal treatment outcomes as well as to
      avoidable side effects of medication.

PMID- 30282575
TI  - In Reply.

PMID- 30282576
TI  - Massive Mucoid Impactions in a 73-Year-Old Woman.

PMID- 30282577
TI  - Supplementary Therapeutic Recommendations.

PMID- 30282578
TI  - In Reply.

PMID- 30282579
TI  - Ocular Torticollis.

PMID- 30282580
TI  - In Reply.

PMID- 30282581
TI  - Deep Burns from Nd:YAG Laser Treatment for Tattoo Removal.

PMID- 30282582
TI  - Discovery of Morgagni Hernia During Screening Colonoscopy.

PMID- 30282584
TI  - Application of urinary proteomics as possible risk predictor of renal and
      cardiovascular complications in patients with type 2-diabetes and
      microalbuminuria.
AB  - BACKGROUND: Analyses of the urinary proteome have been proposed as a novel
      approach for early assessment of increased risk of renal- or cardiovascular
      disease. Here we investigate the potentials of various classifiers derived from
      urinary proteomics for prediction of renal and cardiovascular comorbidities in
      patients with type 2-diabetes. METHODS: The study was a post hoc analysis of the
      randomized controlled Steno-2 trial comparing intensified multifactorial
      intervention to conventional treatment of type 2-diabetes and microalbuminuria.
      151 diabetic patients with persistent microalbuminuria were included in year 1995
      and followed for up to 19 years. For renal outcomes, two classifiers (CKD273 and
      a novel, GFR-based classifier) and for cardiovascular outcomes, three classifiers
      (CAD238, ACSP and ACSP75) were applied. Renal endpoints were progression to
      macroalbuminuria, impaired renal function (GFR < 45 ml/min/1.73 m2) or
      progression to end stage renal disease (ESRD) or death. Cardiovascular endpoints
      were coronary artery disease and a composite endpoint of incident death of
      cardiovascular disease, myocardial infarction or revascularization, stroke,
      amputation or peripheral revascularization. RESULTS: CKD273 was not consistently
      associated with renal outcomes. The GFR-based classifier was associated with
      impaired renal function, but lost significance in extensively adjusted models.
      Both the ACSP75 and ACSP-scores, but not the CAD238-score were inversely
      associated (opposing the hypothesis) with cardiovascular endpoints. None of the
      classifiers improved prediction of any outcome on top of standard risk factors.
      CONCLUSIONS: Risk-scores based upon urinary proteomics did not improve prediction
      of renal and cardiovascular endpoints on top of standard risk factors such as age
      and GFR during long-term (19 years) follow up in patients with type 2-diabetes
      and microalbuminuria.

PMID- 30282583
TI  - The Diagnosis and Treatment of Anxiety Disorders.
AB  - BACKGROUND: Anxiety disorders are the most common type of mental illness in
      Europe, with a 12-month prevalence of 14% among persons aged 14 to 65. Their
      onset is usually in adolescence or early adulthood. The affected patients often
      develop further mental or somatic illnesses (sequential comorbidity). METHODS:
      This review is based on pertinent publications retrieved by a selective search in
      PubMed. RESULTS: The group of anxiety disorders includes generalized anxiety
      disorder (GAD), phobic disorders, panic disorders, and two disorders that are
      often restricted to childhood-separation anxiety and selective mutism. A
      comprehensive differential diag- nostic evaluation is essential, because anxiety
      can be a principal manifestation of other types of mental or somatic illness as
      well. Psychotherapy and treatment with psychoactive drugs are the therapeutic
      strategies of first choice. Of all types of psycho- therapy, cognitive behavioral
      therapy has the best documented efficacy. Modern antidepressants are the drugs of
      first choice for the treatment of panic disorders, agoraphobia, social phobia,
      and GAS; pregabalin is a further drug of first choice for GAS. CONCLUSION: In
      general, anxiety disorders can now be effectively treated. Patients should be
      informed of the therapeutic options and should be involved in treatment planning.
      Current research efforts are centered on individualized and therefore, it is
      hoped, even more effective treatment approaches than are available at present.

PMID- 30282585
TI  - The surgical choice for unilateral thyroid carcinoma in pediatrics: Lobectomy or
      total thyroidectomy?
AB  - BACKGROUND: Total thyroidectomy is no doubt the standard procedure for patients
      with bilateral thyroid carcinoma in pediatrics. However, for lesions confined in
      unilateral thyroid gland, lobectomy or radical total thyroidectomy is still
      controversial in pediatrics. METHODS: Thirty-five cases of pediatric thyroid
      carcinoma which were confirmed by pathology were retrospectively analyzed in our
      hospital from 2005 to 2016. In 13 cases of unilateral lesions, 6 received
      lobectomy, while others underwent total thyroidectomy. Recurrence and
      complications were compared between 2 groups. Also, there were 20 cases of
      primary total thyroidectomy and 4 cases of supplementary resection of the
      residual gland. The short-term complications were compared. RESULTS: There were
      no differences between groups of lobectomy and total thyroidectomy in size,
      extrathyroid extension, stage, cervical lymph nodes metastases, and distant
      metastases. They were the same in incidence of postoperative hypocalcemia,
      calcium supplement, recurrent laryngeal nerve damage, and recurrence rate and
      mortality, except that the length of stay in hospital was shorter in lobectomy
      group. Patients in supplementary resection were more likely to present the
      symptoms of postoperative hypocalcemia and hypokalemia, and it was difficult to
      identify the parathyroid gland during the operation by comparing with patients of
      primary total thyroidectomy. CONCLUSIONS: Thyroid carcinoma in pediatrics is
      inclined to be multifocal, and even in a single focus, the volume is large. Total
      thyroidectomy does not bring more complications. In contrast, the morbidity
      increases in staged resection. Endocrine hormone supplement can satisfy the need
      for growth and development. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE:
      Level III.

PMID- 30282586
TI  - Cervical Pott's disease revealed by retropharyngeal abcess.

PMID- 30282587
TI  - Evaluation of the accuracy of musculoskeletal simulation during squats by means
      of instrumented knee prostheses.
AB  - Standard musculoskeletal simulation tools now offer widespread access to internal
      loading conditions for use in improving rehabilitation concepts or training
      programmes. However, despite broad reliance on their outcome, the accuracy of
      such loading estimations, specifically in deep knee flexion, remains generally
      unknown. The aim of this study was to evaluate the error of tibio-femoral joint
      contact force (JCF) calculations using musculoskeletal simulation compared to in
      vivo measured JCFs in subjects with instrumented total knee endoprostheses during
      squat exercises. Using the early but common "Gait2392_simbody" (OpenSim) scaled
      musculoskeletal models, tibio-femoral JCFs were calculated in 6 subjects for 5
      repetitions of squats. Tibio-femoral JCFs of 0.8-3.2 times bodyweight (BW) were
      measured. While the musculoskeletal simulations underestimated the measured knee
      JCFs at low flexion angles, an average error of less than 20% was achieved
      between approximately 25 degrees -60 degrees  knee flexion. With an average error
      that behaved almost linearly with knee flexion angle, an overestimation of
      approximately 60% was observed at deep flexion (ca. 80 degrees ), with an
      absolute maximum error of ca. 1.9BW. Our data indicate that loading estimations
      from early musculoskeletal gait models at both high and low knee joint flexion
      angles should be interpreted carefully.

PMID- 30282588
TI  - Luminal esophageal temperature monitoring to reduce esophageal thermal injury
      during catheter ablation for atrial fibrillation: A review.
AB  - Over the past decade, catheter ablation for atrial fibrillation has emerged as an
      important rhythm control strategy. One of the most dreaded complications of this
      procedure is atrio-esophageal (AE) fistula formation, which is relatively rare
      but usually fatal. Esophageal tissue injury during ablation appears to be a
      precursor to the formation of AE fistulae. Luminal esophageal temperature (LET)
      monitoring is one of the most commonly utilized strategies to mitigate this risk,
      despite little evidence that it reduces esophageal injury. The incidence of AE
      fistulae appears to be on the rise, despite the widespread use of LET monitoring.
      This may be due to the advent of improved large lesion technology including force
      sensing catheters and the use of high power, although AE fistulae have also been
      observed with the use of low power along the left atrial posterior wall.
      Currently available discrete sensors probes, whether single or multiple, do not
      appear to significantly reduce injury rates. The purpose of this manuscript is to
      systematically review the incidence of esophageal thermal injury with and without
      LET monitoring and review the factors that may be associated with increased risk
      of injury.

PMID- 30282589
TI  - Trends of cost-effectiveness studies in sleep medicine.
AB  - Economic analyses, and cost-effectiveness studies in particular, are increasingly
      used in medicine and population health to inform policy making and resource
      allocation. Health economic models have successfully captured sleep medicine
      outcomes. This study provides an overview of the growth of the use of cost
      effectiveness analyses to quantify the outcomes of sleep related interventions.
      It also identifies highly prevalent sleep disorders, which despite having a high
      burden of disease, lack basic utility studies.

PMID- 30282590
TI  - Precision Medicine through Antisense Oligonucleotide-Mediated Exon Skipping.
AB  - Clinical implementation of two recently approved antisense RNA therapeutics -
      Exondys51(r) to treat Duchenne muscular dystrophy (Duchenne MD) and Spinraza(r)
      as a treatment for spinal muscular atrophy (SMA) - highlights the therapeutic
      potential of antisense oligonucleotides (ASOs). As shown in the Duchenne and
      Becker cases, the identification and specific removal of 'dispensable' exons by
      exon-skipping ASOs could potentially bypass lethal mutations in other genes and
      bring clinical benefits to affected individuals carrying amenable mutations. In
      this review, we discuss the potential of therapeutic alternative splicing, with a
      particular focus on targeted exon skipping using Duchenne MD as an example, and
      speculate on new applications for other inherited rare diseases where redundant
      or dispensable exons may be amenable to exon-skipping ASO intervention as
      precision medicine.

PMID- 30282591
TI  - Time to chemotherapy in ovarian cancer: Compliance with ovarian cancer quality
      indicators at a National Cancer Institute-designated Comprehensive Cancer Center.
AB  - OBJECTIVE: To assess compliance with, and outcomes related to, the Society of
      Gynecologic Oncology quality measure in ovarian cancer to administer chemotherapy
      within 42 days of cytoreductive surgery in patients with epithelial
      ovarian/fallopian tube/peritoneal cancer. METHODS: Institutional ovarian cancer
      database was evaluated for compliance with the quality measure to administer
      chemotherapy within 42 days of cytoreductive surgery. The influence of
      chemotherapy timing on the risk of death was evaluated, and factors related to
      the timing of chemotherapy after surgery was assessed. RESULTS: Of 668 patients
      with epithelial ovarian/fallopian tube/peritoneal cancer who underwent surgical
      treatment for their disease (primary or interval), 635 met criteria for
      administration of adjuvant chemotherapy (with stages IA/IB, grade 2 or 3 disease;
      stage IC or more advanced stage disease). Compliance to administer chemotherapy
      within 42 days was 59.1%. The adjusted risk of death was not strongly associated
      with time to chemotherapy within 42 days (aHR: 0.80; 0.61, 1.05) and this did not
      differ by primary or interval debulking surgery. CONCLUSIONS: In this
      prospectively maintained database, 59.1% of patients received chemotherapy within
      42 days of surgery. The time to chemotherapy interval of within 42 days was not
      strongly associated with improved survival, particularly when age, stage of
      disease, insurance enrollment and surgical characteristics were taken into
      account. Further, the relationship between time to chemotherapy interval of
      within 42 days and survival did not vary by patients who received primary versus
      interval debulking surgery or had no residual disease.

PMID- 30282592
TI  - Guidelines for Performing a Comprehensive Transthoracic Echocardiographic
      Examination in Adults: Recommendations from the American Society of
      Echocardiography.

PMID- 30282593
TI  - Intervention for reducing epilepsy-associated stigma.

PMID- 30282594
TI  - Toward a unified "quality" framework for cell-based therapies.

PMID- 30282595
TI  - The Learning Process of Endoscopic Spinal Surgery for Degenerative Cervical and
      Lumbar Disorders Using the EasyGO! System.
AB  - BACKGROUND: Among spinal surgeons, the safety of endoscopic spinal techniques has
      been criticized as the result of a prolonged learning curve and divergent
      surgical technique from traditional microsurgery. In this manuscript, the authors
      assessed the learning curve of 4 experienced microsurgical neurosurgeons in
      endoscopic spinal surgery. METHODS: Retrospectively, the surgical reports, the
      endoscopic video recording, and the files of all patients who underwent an
      endoscopic procedure for the treatment of cervical and lumbar disc herniation
      from January 2011 to December 2017 were reviewed. The learning process was
      assessed via several parameters: surgical time, intraoperative complications,
      dural tear, nerve root injury, conversion to microsurgery, new postoperative
      neurologic deficits, repeated procedure, and early recurrent disc herniation.
      RESULTS: The learning process of for 4 surgeons was assessed on the basis of 308
      procedures. The mean surgical time for the initial procedure ranges from 58 to 97
      minutes and improved to 51-85 minutes for the last procedures. A shorter surgical
      time had no influence on the rate of intraoperative complication and repeated
      procedure. Increased working space had a significant influence on the surgical
      time. The number of procedure to reach the asymptote varied from 10 to 20
      depending on the endoscopic system and the surgeon. CONCLUSIONS: The learning
      process in endoscopic tubular-assisted spinal surgery is variable, and the
      asymptote might be reached after 10-20 procedures. The amount of working space
      and instrument angulation affects the surgical time. The decrease of surgical
      time had no significant influence on the rate of intraoperative complication and
      repeated procedures.

PMID- 30282596
TI  - Comment on "How to assess the volume of a DIEP flap using a free online
      calculator: The DIEP V (volume) method".

PMID- 30282597
TI  - Percutaneous closure of patent foramen ovale in patients with cryptogenic stroke 
      An updated comprehensive meta-analysis.
AB  - BACKGROUND: The ideal treatment strategy for patients with cryptogenic stroke and
      patent foramen ovale (PFO) is not yet clear. Previous randomized controlled
      trials (RCTs) comparing transcatheter PFO closure with medical therapy in
      patients with cryptogenic stroke to prevent recurrent ischemic stroke showed
      mixed results. This meta-analysis aims to compare rates of recurrent stroke,
      transient ischemic attack (TIA) and all-cause mortality with PFO closure and
      medical therapy vs. medical therapy alone. METHODS: PubMed and the Cochrane
      Center Register of Controlled Trials were searched for studies published through
      June 2018, comparing PFO closure plus medical therapy versus medical therapy
      alone. Six RCTs (n = 3750) comparing PFO closure with medical therapy were
      included in the analysis. End points were recurrent stroke, TIA and all-cause
      mortality. The odds ratios (OR) with 95% confidence interval (CI) were computed
      and p < 0.05 was considered as a level of significance. RESULTS: A total of 1889
      patients were assigned to PFO closure plus medical therapy and 1861 patients were
      assigned to medical therapy only. Risk of recurrent stroke was significantly
      lower in the PFO closure plus medical therapy group compared to medical therapy
      alone. (OR 0.47, 95% CI 0.33-0.67, p < 0.0001). Rate of TIA was similar between
      the two groups (OR 0.76, 95% CI 0.52-1.14), p = 0.18). There was no difference in
      all-cause mortality between two groups (OR 0.73, CI 0.33-1.58, p = 0.42).
      Patients undergoing PFO closure were more likely to develop transient atrial
      fibrillation than medical therapy alone (OR: 5.85; CI: 3.06-11.18, p <=0.0001)
      whereas the risk of bleeding was similar between the groups (OR: 0.93; CI: 0.55
      1.57, p = 0.78). CONCLUSIONS: The results of this meta-analysis suggest that
      transcatheter closure of PFO plus medical therapy is superior to medical therapy
      alone for the prevention of recurrent cryptogenic stroke. However, PFO closure in
      these patients has not been shown to reduce the risk of recurrent TIA or all
      cause mortality. There is a higher rate of transient atrial fibrillation post PFO
      closure device placement, the long-term effects of which have yet to be studied.

PMID- 30282598
TI  - Relation of Anterior Cruciate Ligament Tears to Potential Chronic Cardiovascular
      diseases.
AB  - We have enrolled a cohort of former National Football League players (n = 3,506)
      who played since 1960 to assess potential long term health consequences
      associated with participating in the sport. Each participant has completed a self
      administered questionnaire including reporting of physician-diagnosed health
      conditions. One of the early assessments was to evaluate whether anterior
      cruciate ligament (ACL) tears were associated with later life co-morbidities,
      including cardiovascular effects. We used Cox proportional hazards to estimate
      hazard ratios (HR) for joint replacement surgeries, myocardial infarction, sleep
      apnea, arthritis, dementia, and stroke by history of ACL tear during their
      professional career. For additional outcomes without date of occurrence reported
      we used logistic regression to estimate odds ratios adjusted for potential
      confounding variables in all models. After adjusting for covariates, former
      National Football League players who tore their ACL had approximately a twofold
      increase in muscular skeletal co-morbidities, including knee joint replacement
      and arthritis, compared with those without ACL tears. In addition, those with a
      history of ACL tears also had more than a 50% increased risk of myocardial
      infarction (HR 1.52; 95% confidence interval 0.97 to 2.38) and a slight increase
      in sleep apnea (HR 1.15; 95% confidence interval 0.96 to 1.38). ACL tears
      sustained by athletes may increase the risk of co-morbidities beyond the
      musculoskeletal system. As there are more than 100,000 ACL reconstructions
      annually in the United States, our findings could have widespread public health
      importance if these findings generalize to a population beyond professional
      football players. In conclusion, enhanced screening for other risk factors for
      these conditions in patients who have torn their ACL might identify those who
      could most benefit from prevention strategies.

PMID- 30282599
TI  - Potassium levels and risk of in-hospital arrhythmias and mortality in patients
      admitted with suspected acute coronary syndrome.
AB  - BACKGROUND: In acute coronary syndrome (ACS), potassium imbalance at admission
      has been associated with in-hospital arrhythmias, cardiac arrest, and mortality.
      However, several important presentation characteristics and subtype of ACS have
      not been considered. METHODS: Consecutive patients (n = 32,955) admitted with
      suspected ACS between 2006 and 2011, registered in the Swedish Web-System for
      Enhancement and Development of Evidence-Based care in Heart Disease Evaluated
      According to Recommended Therapies (SWEDEHEART) and the Stockholm CREAtinine
      Measurements (SCREAM) project were included. Associations between admission
      plasma potassium categories (reference 3.5-<4.0 mmol/L) and in-hospital outcomes
      including mortality, cardiac arrest, new-onset atrial fibrillation, and second-
      or third-degree atrioventricular block were assessed with logistic regression
      models. Covariates included demographics, presentation characteristics,
      comorbidities, estimated glomerular filtration rate (eGFR), main diagnosis, and
      medication on admission. RESULTS: U-shaped associations between admission
      potassium, mortality and cardiac arrest were observed. However, in fully adjusted
      models, only hyperkalemia (5.0-<5.5 [OR 1.83; 95% CI, 1.34-2.49] and >=5.5 mmol/L
      [OR 2.27; 95% CI, 1.57-3.27]) was associated with mortality, while only
      hypokalemia (3.0-<3.5 [OR 1.63; 95% CI, 1.21-2.19] and <3.0 mmol/L [OR 2.72; 95%
      CI, 1.56-4.74]) was associated with cardiac arrest. Potassium <3.0 mmol/L (OR
      1.93; 95% CI, 1.00-3.76) was associated with new-onset atrial fibrillation. After
      multivariable adjustment, no association was observed between potassium and
      second- or third-degree atrioventricular block. Results were not modified by main
      diagnosis (ACS subtype or non-ACS diagnosis) or eGFR. CONCLUSIONS: Hyperkalemia
      at admission is associated with in-hospital mortality and hypokalemia with
      cardiac arrest and new-onset atrial fibrillation in patients admitted with
      suspected ACS.

PMID- 30282600
TI  - Differential prognosis of vasospastic angina according to presentation with
      sudden cardiac arrest or not: Analysis of the Korean Health Insurance Review and
      Assessment Service.
AB  - BACKGROUND: The long-term prognosis of vasospastic angina (VSA) patients
      presenting with aborted sudden cardiac death (ASCD) is still unknown. We sought
      to compare the long-term clinical outcomes between VSA patients presenting with
      and without ASCD by retrospective analysis of a nationwide population-based
      database. METHODS: A total of 6972 patients in the Health Insurance Review and
      Assessment database who were hospitalized in the intensive care unit with VSA
      between July 1, 2007 and May 31, 2015 were enrolled. Primary outcome was the
      composite of cardiac arrest and acute myocardial infarction after discharge.
      RESULTS: Five hundred ninety-eight (8.6%) VSA patients presented with ASCD. On
      inverse probability of treatment weighting, ASCD patients had a significantly
      increased risk of the composite of cardiac arrest and acute myocardial infarction
      (adjusted hazard ratio, 2.52; 95% confidence interval, 1.72-3.67; p < 0.001)
      during the median follow-up duration of 4 years. The association of ASCD
      presentation with a worse outcome in terms of primary outcome was consistent
      across various subgroups, including comorbidity type and use of vasodilators (all
      p-values for interaction: non-significant). ASCD patients treated with an
      implantable cardioverter defibrillator (ICD) had a lower incidence of the
      composite of cardiac arrest and acute myocardial infarction during follow-up than
      those without an ICD (p = 0.009). CONCLUSIONS: VSA patients that present with
      ASCD are at increased risk of cardiac arrest or myocardial infarction during long
      term follow-up despite adequate vasodilator therapy. An ICD is a potential
      therapeutic option for secondary prevention.

PMID- 30282601
TI  - Accuracy of cadmium-zinc-telluride imaging in detecting single and multivessel
      coronary artery disease: Is there any gender difference?
AB  - PURPOSE: To evaluate gender-related differences in diagnostic accuracy of cadmium
      zinc-telluride (CZT) myocardial perfusion imaging in detecting single- and multi
      vessel coronary artery disease (CAD). METHODS: We prospectively enrolled 1161
      consecutive patients with known or suspected coronary artery disease (288, 25%
      women and 873, 75% men) who had been referred to our laboratory for stress-rest
      myocardial perfusion imaging (single-day stress-rest protocol, mean radiation
      dose: 4 mSv). All patients underwent coronary angiography within 30 days;
      significant CAD was defined in the presence of a coronary stenosis >70%. Summed
      stress scores (SSS), summed rest scores (SRS) and summed difference scores (SDS)
      were obtained. Image quality was graded "good" or better in >90% of patients.
      RESULTS: On coronary angiography, left main trunk, left anterior descending
      artery, left circumflex artery and right coronary artery obstructive stenosis
      were seen in 13, 486, 393 and 499 patients, respectively. Global SSS was the best
      predictor of CAD in women (AUC = 0.866, 81% sensitivity and 79% specificity) and
      in men (AUC = 0.871, 76% sensitivity and 84% specificity). Interestingly, its
      accuracy was maintained also in patients with two-vessel (women: AUC = 0.842, p <
      0.001; men: AUC 0.839, p < 0.001) or three-vessel disease (women: AUC = 0.800, p
      < 0.001; men: AUC 0.804, p < 0.001). There was no gender-related difference in
      terms of diagnostic accuracy. CONCLUSIONS: Evaluation of multivessel disease can
      be obtained by CZT camera in men as well as in women, with high accuracy at a
      lower radiation exposure.

PMID- 30282602
TI  - Midregional pro-A-type natriuretic peptide as part of a dual biomarker strategy
      for the early rule out of non-ST segment elevation acute coronary syndrome - The
      WilCop study.
AB  - BACKGROUND: Mr-proANP is a biomarker produced in atrial and left ventricular
      myocardium. We investigated the effect of combined measurement of mr-proANP and
      high-sensitive cardiac Troponin I assay of the penultimate generation (s-cTnI)
      for an early type-1 and type-2 NSTE-ACS rule-out with emphasis on the very early
      presenters' subgroup with symptom onset time (SOT) <= 2 h. METHODS: This was a
      prospective cohort study of 311 consecutive patients admitted to ER with symptoms
      suggestive of an acute coronary syndrome (ACS). All patients had baseline mr
      proANP and s-cTnI measurements. RESULTS: Of the total cohort, 17.6% (n = 55) had
      final diagnosis of NSTE-ACS: 9.6% (n = 30) had an angiographically-confirmed type
      1 infarction and 8.0% (n = 25) had type-2 infarction. In the subgroup of very
      early presenters (SOT <= 2 h) the negative predictive value (NPV) of s-cTnI for
      type-1 NSTE-ACS was 96.7% (95%-CI: 87.5-99.4) and the NPV of mr-proANP was 100%
      (95%-CI: 87.1-100). The dual biomarker strategy yielded an NPV of 100% (95%-CI:
      86.7-100). In the same time-related subgroup, the NPV of s-cTnI alone for type-2
      was 98.3% (95%-CI: 89.8-99.9) and the NPV of mr-proANP was 97.0% (95%-CI: 82.5
      100). The combination of biomarker increased the NPV to 100% (95%-CI: 86.7-100).
      CONCLUSIONS: Our study demonstrated an immediate release pattern of mr-proANP in
      NSTE-ACS that may bridge the silent troponin time phenomenon when highest
      sensitivity cardiac troponin assays are not used. This concept performed best in
      the very early presenters' subgroup with an excellent NPV of 100% and might
      result in an early rule-out of NSTE-ACS thus accelerating the diagnostic work-up.

PMID- 30282604
TI  - Optimising the accuracy of HIV drug resistance assays.

PMID- 30282605
TI  - Peroxidase activity of cytochrome c in its compact state depends on dynamics of
      the heme region.
AB  - Cytochrome c (cyt c) is a small globular hemoprotein with the main function as an
      electron carrier in mitochondrial respiratory chain. Cyt c possesses also
      peroxidase-like activity in the native state despite its six-coordinated heme
      iron. In this work, we studied the effect of increasing urea concentration in the
      range from 0 M to 6 M at pH 7 (pH value of the bulk solvent) and pH 5 (pH value
      close to negatively charged membrane) on peroxidase-like activity of cyt c. We
      show that peroxidase-like activity, measured by guaiacol oxidation and the
      ferrous oxidation in xylenol orange methods, correlates with the accessibility of
      the heme iron, which was assessed from the association rate constant of cyanide
      binding to cyt c. Cyt c peroxidase-like activity linearly increases in the pre
      denaturational urea concentrations (0-4 M) at both studied pHs without an
      apparent formation of penta-coordinated state of the heme iron. Our results
      suggest that dynamic equilibrium among the denaturant-induced non-native
      coordination states of cyt c, very likely due to reversible unfolding of the
      least stable foldons, is pre-requisite for enhanced peroxidase-like activity of
      cyt c in its compact state. Dynamic replacement of the native sixth coordination
      bond of methionine-80 by lysines (72, 73, and 79) and partially also by
      histidines (26 and 33) provides an efficient way how to increase peroxidase-like
      activity of cyt c without significant conformational change at physiological
      conditions.

PMID- 30282603
TI  - Clinically relevant thresholds for ultrasensitive HIV drug resistance testing: a
      multi-country nested case-control study.
AB  - BACKGROUND: Implementation of ultrasensitive HIV drug resistance tests for
      routine clinical use is hampered by uncertainty about the clinical relevance of
      drug-resistant minority variants. We assessed different detection thresholds for
      pretreatment drug resistance to predict an increased risk of virological failure.
      METHODS: We did a case-control study nested within a prospective multicountry
      cohort. Our study included patients from 12 clinical sites in Kenya, Nigeria,
      South Africa, Uganda, and Zambia. We defined cases as patients with virological
      failure (ie, those who had either viral load >=400 copies per mL at 12 months or
      had switched to second-line antiretroviral therapy [ART] as a result of
      virological failure before 12 months) and controls as those with viral
      suppression (viral load <400 copies per mL at 12 months) on first-line non
      nucleoside reverse transcriptase inhibitor-based antiretroviral therapy. We
      assessed pretreatment drug resistance with Illumina MiSeq next-generation
      sequencing, using the International Antiviral Society (IAS)-USA mutation list or
      the Stanford HIV Drug Resistance Database (HIVDB) genotypic sensitivity score. We
      calculated diagnostic accuracy measures and assessed the odds of virological
      failure using conditional logistic regression for 1%, 5%, and 10% pretreatment
      drug resistance detection thresholds, compared with the conventional 20% or more
      used in Sanger-based sequencing. FINDINGS: Paired viral load results before ART
      and at month 12 of follow-up were available from 1896 participants. We identified
      178 patients with virological failure and selected 338 matched controls. We
      excluded 117 patients from pretreatment drug resistance analysis; therefore, 152
      cases of virological failure and 247 controls were included in the final
      analysis. With the IAS-USA mutation list, at a detection threshold of 20% or more
      in patients with pretreatment drug resistance, the adjusted odds ratio (OR) for
      virological failure was 9.2 (95% CI 4.2-20.1) compared with those without
      pretreatment drug resistance. Lowering the threshold resulted in adjusted ORs of
      virological failure of 6.8 (95% CI 3.3-13.9) at the 10% threshold, 7.6 (3.4-17.1)
      at the 5% threshold, and 4.5 (2.0-10.2) at the 1% threshold. Lowering the
      detection threshold from 20% improved the sensitivity (ie, ability to identify
      cases) from 12% (n=18) to 13% (n=19) at detection threshold 10%, to 15% (n=23) at
      detection threshold 5%, and to 17% (n=26) at detection threshold 1%, but caused a
      slight reduction in specificity (ie, ability to identify controls) from 98%
      (n=241) to 96% (n=238) at the 10% threshold, 96% (n=236) at the 5% threshold, and
      a larger reduction to 92% (n=227) at the 1% threshold. Diagnostic ORs were 5.4
      (95% CI 2.1-13.9) at the 20% threshold, 3.8 (1.7-8.6) at the 10% threshold, 3.8
      (1.8-8.1) at the 5% threshold, and 2.3 (1.2-4.2) at the 1% threshold. Use of the
      Stanford HIVDB genotypic sensitivity scores yielded similar ORs for virological
      failure, sensitivities, specificities, and diagnostic ORs. INTERPRETATION:
      Ultrasensitive resistance testing for pretreatment drug resistance improved
      identification of people at risk of virological failure; however, this came with
      a reduction in our ability to identify people with viral suppression, especially
      at very low thresholds. Further modelling is needed to estimate the optimal trade
      off for the 5% and 20% thresholds, balancing improved case finding against
      unnecessary regimen switching. FUNDING: The Netherlands Ministry of Foreign
      Affairs, IrsiCaixa, and European Union.

PMID- 30282606
TI  - Improved substrate specificity for D-galactose of L-arabinose isomerase for
      industrial application.
AB  - L-Arabinose isomerase isolated from Geobacillus stearothermophilus (GSAI) was
      modified to improve its substrate specificity for D-galactose for the production
      of D-tagatose, a potential reduced-energy sweetener. Among the selected residues,
      mutation at residue 18 produced a mutant strain, H18T, which exhibited increased
      activity for D-galactose compared with the wild-type (WT) enzyme. Analysis of the
      substrate specificity of H18T showed a 45.4% improvement for D-galactose.
      Replacing histidine with threonine at residue 18 resulted in approximately 2.7
      fold and 1.8-fold higher substrate binding and catalytic efficiency,
      respectively, for D-galactose. Further enhancement of the specific activity and
      catalytic efficiency of H18T for D-galactose by up to 2.7-fold and 4.3-fold,
      respectively, was achieved by adding borate during L-arabinose isomerase
      catalysis. Moreover, H18T showed thermostability and no destabilization was
      detected, which is promising for the industrial production of D-tagatose.

PMID- 30282607
TI  - Proteomic analyses reveal GNG12 regulates cell growth and casein synthesis by
      activating the Leu-mediated mTORC1 signaling pathway.
AB  - In cow mammary epithelial cells (CMECs), cell growth and casein synthesis are
      regulated by amino acids (AAs), and lysosomes are important organelles in this
      regulatory process, but the mechanisms remain unclear. Herein, lysosomal membrane
      proteins (LMPs) in CMECs in the presence (Leu+) and absence (Leu-) of leucine
      were quantitatively analysed using Sequential Windowed Acquisition of All
      Theoretical Fragment Ion (SWATH) mass spectrometry. In identified LMPs, Guanine
      nucleotide-binding protein subunit gamma-12 (GNG12) was a markedly up-regulated
      protein in Leu+ group. CMECs were treated with Leu+ or Leu-, expression and
      lysosomal localization of GNG12 were decreased in response to Leu absence.
      Overexpressing or inhibiting GNG12 demonstrated that cell growth, casein
      synthesis and activation of the mammalian target of rapamycin complex 1 (mTORC1)
      signaling pathway were all up-regulated by GNG12. Cell growth, casein synthesis
      and mTORC1 signaling pathway were decreased in response to Leu absence, but these
      decreases were partially restored by GNG12 overexpression, and those effects were
      partially reversed by inhibiting GNG12. Co-immunoprecipitation analysis showed
      that GNG12 activates the mTORC1 pathway via interaction with Ragulator. Taken
      together, these results suggest that GNG12 is a positive regulator of the Leu
      mediated mTORC1 signaling pathway in CMECs that promotes cell growth and casein
      synthesis.

PMID- 30282608
TI  - Macromolecular crowding-induced molten globule states of the alkali pH-denatured
      proteins.
AB  - Structural and molecular properties extracted from circular dichroism (CD),
      tryptophan fluorescence and 1-anilino-8-napthalene sulfonate (ANS) binding
      experiments suggest that the high concentration of synthetic crowding agents
      (dextran 40, dextran 70 and ficoll 70) stabilizes and refolds the base-denatured
      ferricytochrome c (Ferricyt c) and lysozyme (Lyz) at pH 12.9 (+/-0.1) to molten
      globule (MG) states (CB-states). These results further revealed that the CB
      states resemble the generic properties of MG-states. Thermodynamic analysis of
      thermal denaturation curves of base-denatured Ferricyt c and Lyz at pH 12.9 (+/
      0.1) under variable concentrations of crowding agents (dextran 40, dextran 70 and
      ficoll 70) revealed that the crowder presence increases the thermal stability of
      base-denatured proteins and also prevents the cold denaturation of Ferricyt c.
      The results further showed that the nature, size and shape of crowder influence
      the crowding-mediated increase in secondary structure stabilization and thermal
      stability of base-denatured Ferricyt c and Lyz. Analysis of kinetic and
      thermodynamic parameters measured for CO association reaction of alkaline
      ferrocytochrome c (Ferrocyt c) at pH 12.9 (+/-0.1) under variable concentrations
      of crowding agents (dextran 40, dextran 70 and ficoll 70) revealed that the
      crowder presence reduces the level of structural fluctuation of M80-containing
      Omega-loop that control CO association to alkaline Ferrocyt c.

PMID- 30282609
TI  - myo-Inositol dehydrogenase and scyllo-inositol dehydrogenase from Lactobacillus
      casei BL23 bind their substrates in very different orientations.
AB  - Many bacteria can use myo-inositol as the sole carbon source using enzymes
      encoded in the iol operon. The first step is catalyzed by the well-characterized
      myo-inositol dehydrogenase (mIDH), which oxidizes the axial hydroxyl group of the
      substrate to form scyllo-inosose. Some bacteria, including Lactobacillus casei,
      contain more than one apparent mIDH-encoding gene in the iol operon, but such
      redundant enzymes have not been investigated. scyllo-Inositol, a stereoisomer of
      myo-inositol, is not a substrate for mIDH, but scyllo-inositol dehydrogenase
      (sIDH) enzymes have been reported, though never observed to be encoded within the
      iol operon. Sequences indicate these enzymes are related, but the structural
      basis by which they distinguish their substrates has not been determined. Here we
      report the substrate selectivity, kinetics, and high-resolution crystal
      structures of the proteins encoded by iolG1 and iolG2 from L. casei BL23, which
      we show encode a mIDH and sIDH, respectively. Comparison of the ternary complex
      of each enzyme with its preferred substrate reveals the key variations allowing
      for oxidation of an equatorial versus an axial hydroxyl group. Despite the
      overall similarity of the active site residues, scyllo-inositol is bound in an
      inverted, tilted orientation by sIDH relative to the orientation of myo-inositol
      by mIDH.

PMID- 30282610
TI  - Structural and functional analysis of miraculin-like protein from Vitis vinifera.
AB  - The so-called miraculin-like proteins (MLPs) are homologous to miraculin, a
      homodimeric protein with taste-modifying activity that converts sourness into
      sweetness. The identity between MLPs and miraculin generally ranges from 30% to
      55%, and both MLPs and miraculin are categorized into the Kunitz-type soybean
      trypsin inhibitor (STI) family. MLP from grape (Vitis vinifera; vvMLP) exhibits
      significant homology to miraculin (61% identity), suggesting that vvMLP possesses
      miraculin-like properties. The results of size-exclusion chromatography and
      sensory analysis illustrated that vvMLP exists as a monomer in solution with no
      detectable taste-modifying activity. Crystal structure determination revealed
      that vvMLP exists as a beta-trefoil fold, similarly as other MLPs and Kunitz-type
      protein inhibitors. The conformation of the loops, including the so-called
      reactive loop in the STI family, was substantially different between vvMLP and
      STI. Recombinant vvMLP had inhibitory activity against trypsin (Ki = 13.7 MUM),
      indicating that the protein can act as a moderate trypsin inhibitor.

PMID- 30282611
TI  - Biochemical and biophysical characterization of 1,4-naphthoquinone as a dual
      inhibitor of two key enzymes of type II fatty acid biosynthesis from Moraxella
      catarrhalis.
AB  - The fatty acid biosynthesis (FAS II) is a vital process in bacteria and regarded
      as an attractive pathway for the development of potential antimicrobial agents.
      In this study, we report 1,4-naphthoquinone (NPQ) as a dual inhibitor of two key
      enzymes of FAS II pathway, namely FabD (Malonyl-CoA:ACP transacylase) and FabZ
      (beta-hydroxyacyl-ACP dehydratase). Mode of inhibition of NPQ was found to be non
      competitive for both enzymes with IC50 of 26.67 MUMU and 23.18 MUMU against
      McFabZ and McFabD respectively. Conformational changes in secondary and tertiary
      structures marked by the loss of helical contents were observed in both enzymes
      upon NPQ binding. The fluorescence quenching was found to be static with a stable
      ground state complex formation. ITC based studies have shown that NPQ is binding
      to McFabZ with a stronger affinity (~1.5*) as compared to McFabD. Molecular
      docking studies have found that NPQ interacts with key residues of both McFabD
      (Ser209, Arg126, and Leu102) and McFabZ (His74 and Tyr112) enzymes. Both
      complexes have shown the structural stability during the 20 ns run of molecular
      dynamics based simulations. Altogether, the present study suggests that NPQ
      scaffold can be exploited as a multi-targeted inhibitor of FAS II pathway, and
      these biochemical and biophysical findings will further help in the development
      of potent antibacterial agents targeting FAS II pathway.

PMID- 30282612
TI  - Binding properties of sterol carrier protein 2 (SCP2) characterized using
      Laurdan.
AB  - Sterol carrier protein 2 (SCP2) binds lipids with high affinity and broad
      specificity. The overall hydrophobicity, fluidity, and dipolar dynamics of the
      binding site of SCP2 from Yarrowia lipolytica were characterized using the
      environmentally-sensitive fluorescent probe Laurdan. The study revealed a binding
      site with an overall polarity similar to that of dichloromethane and an internal
      phase comparable to that of phospholipid membranes with coexisting solid-ordered
      and liquid-crystalline states. The fluorescence properties of bound Laurdan also
      revealed that the binding site of SCP2 can accommodate competitively more than
      one ligand, with micro and nanomolar dissociation constants. The much higher
      affinity for the second than for the first ligand implies that the most prominent
      SCP2 species in the cellular context are those occupied by two ligands. Thus SCP2
      may carry a highly populated lipid in the background and a second one, specific
      for the functional purpose of SCP2. Our findings are important for the
      characterization of SCP2 biological functions and the design of specific
      inhibitors.

PMID- 30282613
TI  - Metal ions-induced stability and function of bimetallic human arginase-I, a
      therapeutically important enzyme.
AB  - Recent studies have highlighted the therapeutic importance of bimetallic human
      arginase-I against hyperargininemia and L-arginine auxotrophic cancers. The
      longer retention of catalytic activity of the Co2+-enzyme than that of the Mn2+
      in human serum is associated with its enhanced therapeutic potential. To
      understand the basis of this and also to explore the role of a bimetallic center
      as well as the role of individual metal ions in the stability, we performed a
      detailed biochemical and biophysical investigation. The thermodynamic and kinetic
      stabilities of both the holo proteins are found to be significantly higher than
      the apo form, indicating that an intact bimetallic centre is vital for the
      enhanced stability of the holo proteins. The Co2+-protein is found to be more
      stable than that of the Mn2+, which might explain its longer retention of
      activity observed in the serum. Mutational studies demonstrated that the metal
      ions are individually crucial for both the enhanced stability and catalytic
      activity. Furthermore, we investigated the underlying mechanism for the effect of
      heat activation on the holo protein for higher catalytic activity, which is not
      yet known for arginases. Our data reveal that heat activation significantly
      increases the stability of the holo protein through a metal-induced increase in
      the helical content leading to the formation of a kinetically competent enzyme.
      Thus, the present study provides an in-depth insight into the significance of
      heat activation and the role of metal ions in human arginase, which may be useful
      for better understanding of its therapeutic use.

PMID- 30282614
TI  - Ordered opening of LDL receptor binding domain of human apolipoprotein E3
      revealed by hydrogen/deuterium exchange mass spectrometry and fluorescence
      spectroscopy.
AB  - Apolipoprotein E3 (apoE3) is an exchangeable apolipoprotein that plays a critical
      role in cholesterol homeostasis. The N-terminal (NT) domain of apoE3 (residues 1
      191) is folded into a helix bundle comprised of 4 amphipathic alpha-helices: H1,
      H2, H3 and H4, flanked by flexible helices N1 and N2, and Hinge Helix 1 (Hinge
      H1), at the N-and C-terminal sides of the helix bundle, respectively. The NT
      domain plays a critical role in binding to the low density lipoprotein receptor
      (LDLR), which eventually leads to lowering of plasma cholesterol levels. In order
      to be recognized by the LDLR, the helix bundle has to open and undergo a
      conformational change. The objective of the study was to understand the mechanism
      of opening of the helix bundle. Hydrogen/deuterium exchange mass spectrometry
      (HDX-MS) revealed that apoE3 NT domain adopts several disordered and unfolded
      regions, with H2 exhibiting relatively little protection against exchange-in
      compared to H1, H3, and H4. Site-directed fluorescence labeling indicated that H2
      not only has the highest degree of solvent exposure but also the most flexibility
      in the helix bundle. It also indicated that the lipoprotein behavior of H1 was
      significnatly different from that of H2, H3 and H4. These results suggest that
      the opening of the helix bundle is likely initiated at the flexible end of H2 and
      the loop linking H2/H3, and involves movement of H2/H3 away from H1/H4. Together,
      these observations offer mechanistic insight suggesting a regulated helix bundle
      opening of apoE3 NT domain can be triggered by lipid binding.

PMID- 30282615
TI  - Processing of high-titer prions for mass spectrometry inactivates prion
      infectivity.
AB  - Prions represent a class of universally fatal and transmissible neurodegenerative
      disorders that affect humans and other mammals. The prion agent contains a
      pathologically aggregated form of the host prion protein that can transmit
      infectivity without any bacterial or viral component and is thus difficult to
      inactivate using disinfection protocols designed for infectious microorganisms.
      Methods for prion inactivation include treatment with acids, bases, detergents,
      bleach, prolonged autoclaving and incineration. During these procedures, the
      sample is often either destroyed or damaged such that further analysis for
      research purposes is compromised. In this study we show that a straightforward
      denaturation and in-gel protease digestion protocol used to prepare prion
      infected samples for mass spectroscopy leads to the loss of at least 7 logs of
      prion infectivity, yielding a final product that fails to transmit prion disease
      in vivo. We further show that the resultant sample remains suitable for mass
      spectrometry-based protein identifications. Thus, the procedure described can be
      used to prepare prion-infected samples for mass spectrometry analysis with
      greatly reduced biosafety concerns.

PMID- 30282616
TI  - Modification of quaternary structure of Candida albicans GlcN-6-P synthase and
      its desensitization to inhibition by UDP-GlcNAc by site-directed mutagenesis.
AB  - Site-directed mutagenesis of the CaGFA1 gene encoding glucosamine-6-phosphate
      synthase from Candida albicans was performed. Desensitization of the enzyme to
      inhibition by UDPGlcNAc was achieved upon T487I and H492F substitutions at the
      UDP-GlcNAc binding site, exchange of D524, S525 and S527 for Ala at the
      dimer:dimer interface and construction of the tail-lock array (L434R and L460A)
      at the C-tail region. The first two sets if mutageneses but not the last one
      resulted in conversion of the tetrameric enzyme into its dimeric form. Evidence
      for links and communication between the UDP-GlcNAc binding site and the dimer
      dimer contact areas are presented. The CaGfa1-T487IH492F and CaGfa1-KHSH
      D524AS525AS527A muteins are the first examples of the successful conversion of
      eukaryotic GlcN-6-P synthase into its prokaryotic-like version upon rational site
      directed mutagenesis.

PMID- 30282617
TI  - The Glucose Control Resistance Scale (GCRS)
AB  - OBJECTIVE: While past research found family conflict, disordered eating, body
      image concerns, and anxious self-doubts may affect glucose control (A1C),
      available measures of adherence mainly focus on management tasks. The goal of the
      current study was to combine emotional distress and beliefs with decisions on
      management in a new measure of adolescent resistance to treatment adherence: the
      12-item Glucose Control Resistance Scale (GCRS). METHODS: Participants included
      135 adolescents and their parents from a pediatric diabetes clinic. Surveys
      measured family conflict, body image concerns, anxious self-doubts, and glucose
      control resistance. RESULTS: Factor analysis showed 12 items with loadings of .40
      or higher to form the Glucose Control Resistance Scale (GCRS). The scale had
      adequate reliability and there was a significant correlation between child and
      parent GCRS scores. One factor, family conflict, was significantly related to A1C
      levels, but the set of four factors explained a total of 12% of the variance in
      A1C levels. Of the adolescent demographic variables considered (gender, number of
      parents at home, age, BMIz), only gender was significantly associated with
      adolescent perceptions of family conflict. CONCLUSION: The GCRS may allow
      diabetic care teams to better understand the origin of family conflict
      perceptions and the motivational beliefs that modify behavior and contribute to
      independent self-management and glucose control. Each question was designed to be
      meaningful in interventions by addressing common items of resistance to adherence
      and impulsive management decisions. The GCRS may be used by providers as an
      initial short screening survey on an annual or semi-annual basis.

PMID- 30282618
TI  - Epicardial fat thickness in children with classic congenital adrenal hyperplasia.
AB  - OBJECTIVE: Epicardial fat thickness (EFT) is an emerging cardiometabolic risk
      factor and has been shown to be related to atherosclerosis. EFT has not been
      studied in the context of CAH. This study aimed to evaluate EFT in children with
      CAH and its relation to carotid intima media thickness (CA-IMT) and left
      ventricular functions. METHODS: 36 children with classic CAH were compared with
      36 healthy controls. All children had confirmed CAH and received steroid
      substitution therapy. Patients and controls underwent anthropometric evaluation,
      measurement of fasting lipids, glucose, insulin, homeostasis model assessment for
      insulin resistance (HOMA-IR), Left ventricular functions and EFT were assessed
      using conventional echocardiography. Duplex ultrasonography was used to measure
      CA-IMT. RESULTS: Compared to controls, patients had higher EFT (p=0.001), HOMA
      IR(p=0.001), CA- IMT (p=0.01), LVMI (p=0.001) and prolonged mitral deceleration
      time (DcT) (p=0.01).Abnormalities were marked in uncontrolled children on medical
      treatment. In multivariate analysis in children with classic CAH , EFT correlated
      positively with waist circumference (OR =1.9,95%Cl=1.07-1.14.p=001), 17-OHP;
      nmol/l (OR =1.6; 95% CI = 1.33-2.89, p = 0.05), testosterone , ng/dl(OR =1.7; 95%
      CI = 1.55-2.13, p = 0.01), LVMI (OR=1.14, 95%Cl=1.08-1.13, p=0.0001) , mitral DcT
      (OR=2.25;95% CI=1.15-2.05, p=0.01) and CA-IMT (OR=1.6 ;95% CI=1.15-2.05, p=0.01).
      CONCLUSIONS: EFT may be elevated in children with classic CAH particularly those
      with poor control and is correlated to carotid intima media thickness, left
      ventricular mass and mitral deceleration time. Measurement of EFT by
      Echocardiography in CAH children may help to identify those at high risk of
      developing left ventricular dysfunction and subclinical atherosclerosis.

PMID- 30282619
TI  - Genetic and clinical characteristics of the patients with Vitamin D Dependent
      Rickets Type 1A.
AB  - OBJECTIVE: Vitamin D dependent rickets type 1A (VDDR1A) is an autosomal recessive
      disorder caused by mutations in the 25OHD 1alpha-hydroxylase gene (CYB27B1). As
      it may be confused with nutritional rickets and hypophosphatemic rickets, genetic
      analysis is important for making a correct diagnosis. METHODS: We analysed
      genomic DNA from 11 patients from 8 different Turkish families. The patients were
      recruited for our studies if they presented with diagnosis of vitamin D dependent
      rickets. RESULTS: The mean age at diagnosis was 13.1 +/-7.4 months. Seven
      patients had mild hypocalcemia at presentation while 4 patients had normal
      calcium levels. All patients underwent CYP27B1 gene analysis; The most prevalent
      mutation was the c.195 + 2T>G splice donor site mutation, affecting 5 out of 11
      patients with VDDR1A. Two patients from the fourth family was compound
      heterozygous for c.195 +2T>G and c.195 +2 T>A in intron 1. Two patients from
      different families were homozygous for a previously reported duplication mutation
      in exon 8 (1319_1325dupCCCACCC, Phe443Profs*24). One patient had homozygous
      splice site mutation in intron 7 (c.1215+2 T>A). And one patient had homozygous
      mutation in exon 9 (c.1474 C>T). CONCLUSION: Intron 1 mutation was the most
      common mutation as in the previous studies, and all patients carrying that
      mutation were from same city of origin suggesting a "founder" or a "common
      ancestor" effect. VDDR1A should be definitely considered when a patient with
      signs of rickets has a normal 25-OH level or when there is unresponsiveness to
      vitamin D treatment.

PMID- 30282620
TI  - Effectiveness of the Malnutrition eLearning Course for Global Capacity Building
      in the Management of Malnutrition: Cross-Country Interrupted Time-Series Study.
AB  - BACKGROUND: Scaling up improved management of severe acute malnutrition has been
      identified as the nutrition intervention with the largest potential to reduce
      child mortality, but lack of operational capacity at all levels of the health
      system constrains scale-up. We therefore developed an interactive malnutrition
      eLearning course that is accessible at scale to build capacity of the health
      sector workforce to manage severely malnourished children according to the
      guidelines of the World Health Organization. OBJECTIVE: The aim of this study was
      to test whether the malnutrition eLearning course improves knowledge and skills
      of in-service and preservice health professionals in managing children with
      severe acute malnutrition and enables them to apply the gained knowledge and
      skills in patient care. METHODS: This 2-year prospective, longitudinal, cross
      country, interrupted time-series study took place in Ghana, Guatemala, El
      Salvador, and Colombia between January 2015 and February 2017. A subset of 354 in
      service health personnel from 12 hospitals and 2 Ministries of Health, 703
      preservice trainees from 9 academic institutions, and 204 online users
      participated. Knowledge gained after training and retention over time was
      measured through pre- and postassessments comprising questions pertaining to
      screening, diagnosis, pathophysiology and treatment, and prevention of
      malnutrition. Comprehension, application, and integration of knowledge were
      tested. Changes in perception, confidence, and clinical practice were assessed
      through questionnaires and interviews. RESULTS: Before the course, awareness of
      the World Health Organization guidelines was 36.73% (389/1059) overall, and 26.3%
      (94/358) among in-service professionals. The mean score gain in knowledge after
      access to the course in 606 participants who had pre- and postassessment data was
      11.8 (95% CI 10.8-12.9; P<.001)-a relative increase of 41.5%. The proportion of
      participants who achieved a score above the pass mark posttraining was 58.7%
      (356/606), compared with 18.2% (110/606) in pretraining. Of the in-service
      professionals, 85.9% (128/149) reported applying their knowledge by changing
      their clinical practice in screening, assessment, diagnosis, and management. This
      group demonstrated significantly increased retained knowledge 6 months after
      training (mean difference [SD] from preassessment of 12.1 [11.8]), retaining
      65.8% (12.1/18.4) of gained knowledge from the training. Changes in the
      management of malnutrition were reported by trained participants, and
      institutional, operational, and policy changes were also found. CONCLUSIONS: The
      malnutrition eLearning course improved knowledge, understanding, and skills of
      health professionals in the diagnosis and management of children with severe
      acute malnutrition, and changes in clinical practice and confidence were reported
      following the completion of the course.

PMID- 30282621
TI  - Behavior Change Techniques in mHealth Apps for the Mental and Physical Health of
      Employees: Systematic Assessment.
AB  - BACKGROUND: Employees remain at risk of developing physical and mental health
      problems. To improve the lifestyle, health, and productivity many workplace
      interventions have been developed. However, not all of these interventions are
      effective. Mobile and wireless technology to support health behavior change
      (mobile health [mHealth] apps) is a promising, but relatively new domain for the
      occupational setting. Research on mHealth apps for the mental and physical health
      of employees is scarce. Interventions are more likely to be useful if they are
      rooted in health behavior change theory. Evaluating the presence of specific
      combinations of behavior change techniques (BCTs) in mHealth apps might be used
      as an indicator of potential quality and effectiveness. OBJECTIVE: The aim of
      this study was to assess whether mHealth apps for the mental and physical health
      of employees incorporate BCTs and, if so, which BCTs can be identified and which
      combinations of BCTs are present. METHODS: An assessment was made of apps aiming
      to reduce the risk of physical and psychosocial work demands and to promote a
      healthy lifestyle for employees. A systematic search was performed in iTunes and
      Google Play. Forty-five apps were screened and downloaded. BCTs were identified
      using a taxonomy applied in similar reviews. The mean and ranges were calculated.
      RESULTS: On average, the apps included 7 of the 26 BCTs (range 2-18). Techniques
      such as "provide feedback on performance," "provide information about behavior
      health link," and "provide instruction" were used most frequently. Techniques
      that were used least were "relapse prevention," "prompt self-talk," "use follow
      up prompts," and "provide information about others' approval." "Stress
      management," "prompt identification as a role model," and "agree on behavioral
      contract" were not used by any of the apps. The combination "provide information
      about behavior-health link" with "prompt intention formation" was found in 7/45
      (16%) apps. The combination "provide information about behavior-health link" with
      "provide information on consequences," and "use follow-up prompts" was found in 2
      (4%) apps. These combinations indicated potential effectiveness. The least
      potentially effective combination "provide feedback on performance" without
      "provide instruction" was found in 13 (29%) apps. CONCLUSIONS: Apps for the
      occupational setting might be substantially improved to increase potential since
      results showed a limited presence of BCTs in general, limited use of potentially
      successful combinations of BCTs in apps, and use of potentially unsuccessful
      combinations of BCTs. Increasing knowledge on the effectiveness of BCTs in apps
      might be used to develop guidelines for app developers and selection criteria for
      companies and individuals. Also, this might contribute to decreasing the burden
      of work-related diseases. To achieve this, app developers, health behavior change
      professionals, experts on physical and mental health, and end-users should
      collaborate when developing apps for the working context.

PMID- 30282622
TI  - Using Mobile Technology (pMOTAR) to Assess Reactogenicity: Protocol for a Pilot
      Randomized Controlled Trial.
AB  - BACKGROUND: Accurate safety monitoring in HIV vaccine trials is vital to eventual
      licensure and consequent uptake of products. Current practice in preventive
      vaccine trials, under the HIV Vaccine Trials Network (HVTN), is to capture
      related side effects in a hardcopy tool. The reconciliation of this tool, 2 weeks
      after vaccination at the safety visit, is time consuming, laborious, and fraught
      with error. Unstructured Supplementary Service Data (USSD), commonly used to
      purchase airtime, has been suggested for collection of safety data in vaccine
      trials. With saturated access to mobile phones in South Africa, this cheap,
      accessible tool may improve accuracy and completeness of collected data and prove
      feasible and acceptable over the hardcopy tool. OBJECTIVE: The objective of our
      study is to develop and implement a USSD tool for real-time safety data
      collection that is feasible and acceptable to participants and staff, allowing
      for a comparison with the hardcopy tool in terms of completeness and accuracy.
      METHODS: This feasibility study is being conducted at a single study site, the
      Centre for the AIDS Programme of Research in South Africa eThekwini Clinical
      Research site, in South Africa. The feasibility study is nested within a parent
      phase 1/2a preventive HIV vaccine trial (HVTN 108) as an open-label, randomized
      controlled trial, open to all consenting parent trial participants. Participants
      are randomly assigned in a 1:1 ratio to the hardcopy or USSD tool, with data
      collection targeted to the third and fourth injection time points in the parent
      trial. Online feasibility and acceptability surveys will be completed by staff
      and participants at the safety visit. We will itemize and compare error rates
      between the hardcopy tool and the USSD printout and associated source
      documentation. We hypothesize that the USSD tool will be shown to be feasible and
      acceptable to staff and participants and to have superior quality and completion
      rates to the hardcopy tool. RESULTS: The study has received regulatory approval.
      We have designed and developed the USSD tool to include all the data fields
      required for reactogenicity reporting. Online feasibility and accessibility
      surveys in both English and isiZulu have been successfully installed on a tablet.
      Data collection is complete, but analysis is pending. CONCLUSIONS: Several HIV
      preventive vaccine trials are active in Southern Africa, making tools to improve
      efficiencies and minimize error necessary. Our results will help to determine
      whether the USSD tool can be used in future vaccine studies and can eventually be
      rolled out. TRIAL REGISTRATION: ClincalTrials.gov NCT02915016;
      https://clinicaltrials.gov/ct2/show/NCT02915016 (Archived by WebCite at
      http://www.webcitation.org/71h0cztDM). REGISTERED REPORT IDENTIFIER: RR1
      10.2196/9396.

PMID- 30282624
TI  - QUESTION 2: Do conservative rates of rehydration in children with diabetic
      ketoacidosis decrease the risk of cerebral oedema?

PMID- 30282623
TI  - Arthritis-Related Support in a Social Media Group for Quilting Hobbyists:
      Qualitative Study.
AB  - BACKGROUND: People with arthritis are increasingly seeking support online,
      particularly for information about social role participation while experiencing
      symptoms of chronic arthritis. Social media enables peer-to-peer support on how
      serious leisure (eg, hobbies such as quilting) can be adapted to allow
      participation. Research is needed to understand what type of peer support is
      provided online and how this support occurs. OBJECTIVE: The aim of our study was
      to explore what kind of support is offered by fellow hobbyists (with or without
      arthritis) in response to requests for advice in a social media group. METHODS:
      Three vignettes were posted on a Facebook quilting group regarding arthritis
      related symptoms or impairments that affect how people quilt. A Facebook Insights
      report was used to examine the groups' demographics. Responses to the vignettes
      were thematically analyzed. RESULTS: The members of the quilting Facebook group
      were mostly women (18,376/18,478, 99.45%), aged 55 to 64 years, and most were
      located in the United States. In response to the vignettes, the 22 participants
      predominantly offered emotional support and shared information. Participants
      shared their real-life experiences and creative means in adapting medical advice
      to their crafting. More than half (30/54, 56%) of the advice that was offered
      aligned with the OrthoInfo medical best practice guidelines relevant to the
      vignettes. CONCLUSIONS: Serious leisure social media groups can be useful forums
      for sharing information about arthritis-related issues. People do respond to
      requests for support and information, although there is a difference between
      quilting support (eg, "I need a new iron, what should I buy?") and health support
      (eg, "I have arthritis, what scissors should I buy?"). People provide emotional
      support for life events on serious leisure social media platforms (eg, offering
      condolences when a person states that she is making a memory quilt), and this
      extends to health issues when group members reveal them.

PMID- 30282625
TI  - Does coagulase negative staphylococcal sepsis cause neurodevelopmental delay in
      preterm infants?

PMID- 30282626
TI  - Quality of life after extremely preterm birth.

PMID- 30282627
TI  - Need for evidence-based early intervention programmes: a public health
      perspective.
AB  - This paper attempts to discuss why the early intervention agenda based on the
      current convention of 'ultra-high risk' (UHR) or 'clinical high risk' (CHR) for
      'transition' to psychosis framework has been destined to fall short of generating
      a measurable and economically feasible public health impact. To summarise: (1)
      the primary determinant of the 'transition' rate is not the predictive value of
      the UHR/CHR but the degree of the risk-enrichment; (2) even with a significant
      pre-test risk enrichment, the prognostic accuracy of the assessment tools in help
      seeking population is mediocre, failing to meet the bare minimum thresholds; (3)
      therapeutic interventions arguably prolong the time-to-onset of psychotic
      symptoms instead of preventing 'transition', given that the UHR/CHR and
      'transition' lie on the same unidimensional scale of positive psychotic symptoms;
      (4) meta-analytical evidence confirms that specific effective treatment for
      preventing 'transition' (the goal-primary outcome-of the UHR/CHR framework) is
      not available; (5) the UHR/CHR-'transition' is a precarious target for research
      given the unpredictability driven by the sampling strategies and the natural ebb
      and flow of psychotic symptoms within and between individuals, leading to false
      positives; (6) only a negligible portion of those who develop psychosis benefits
      from UHR/CHR services (see prevention paradox); (7) limited data on the cost
      effectiveness of these services exist. Given the pitfalls of the narrow focus of
      the UHR/CHR framework, a broader prevention strategy embracing pluripotency of
      early psychopathology seems to serve as a better alternative. Nevertheless, there
      is a need for economic evaluation of these extended transdiagnostic early
      intervention programmes.

PMID- 30282628
TI  - Cochrane examines whether lead author of HPV review had undeclared conflicts of
      interest.

PMID- 30282629
TI  - Defining significant childhood illness and injury in the Emergency Department: a
      consensus of UK and Ireland expert opinion.
AB  - BACKGROUND: Clarifying whether paediatric early warning scores (PEWS) accurately
      predict significant illness is a research priority for UK and Ireland paediatric
      emergency medicine (EM). However, a standardised list of significant conditions
      to benchmark these scores does not exist. OBJECTIVES: To establish standardised
      significant illness endpoints for use in determining the performance accuracy of
      PEWS and safety systems in emergency departments (ED), using a consensus of
      expert opinion in the UK and Ireland. DESIGN: Between July 2017 and February
      2018, three online Delphi rounds established a consensus on 'significant'
      clinical conditions, derived from a list of common childhood illness/injury ED
      presentations. Conditions warranting acute hospital admission in the opinion of
      the respondent were defined as 'significant', using a 5-point Likert scale. The
      consensus was a priori >=80% (positive or negative). 258 clinical conditions were
      tested. PARTICIPANTS AND SETTINGS: Eligible participants were consultants in
      acute or EM paediatrics, or adult EM, accessed via 53 PERUKI (Paediatric
      Emergency Research in the UK and Ireland)'s research collaborative sites, and 27
      GAPRUKI (General and Adolescent Paediatric Research in the UK and Ireland)'s
      sites, 17 of which overlap with PERUKI. MAIN OUTCOME MEASURES: To create a list
      of conditions regarded as 'significant'with >=80% expert consensus. RESULTS: 43
      (68%) of 63 PERUKI and GAPRUKI sites responded; 295 experts were invited to
      participate. Participants in rounds 1, 2 and 3 were 223 (76%), 177 (60%) and 148
      (50%), respectively; 154 conditions reached positive consensus as 'significant';
      1 condition reached a negative consensus (uncomplicated Henoch-Schonlein
      purpura); and 37 conditions achieved non-consensus. CONCLUSIONS: A list of
      significant childhood conditions has been created using UK and Irish expert
      consensus, for research purposes, for the first time. This will be used as the
      benchmark endpoint list for future research into PEWS/safety systems performance
      in EDs.

PMID- 30282630
TI  - Symptom-triggered therapy for assessment and management of alcohol withdrawal
      syndrome in the emergency department short-stay clinical decision unit.
AB  - INTRODUCTION: We previously reported that benzodiazepine detoxification for
      alcohol withdrawal using symptom-triggered therapy (STT) with oral diazepam
      reduced length of stay (LOS) and cumulative benzodiazepine dose by comparison
      with standard fixed-dose regimen. In this study, we aim to describe the
      feasibility of STT in an emergency department (ED) short-stay clinical decision
      unit (CDU) setting. METHODS: In this retrospective cohort study, we describe our
      experience with STT over a full calendar year (2014) in the CDU. A retrospective
      chart review was conducted and data collection included demographics, clinical
      details, total cumulative dose of diazepam, receipt of parenteral thiamine, LOS
      and disposition. RESULTS: 5% (n=174) of 3222 admissions to CDU required STT.
      Collapse or seizure (41%, n=71) and alcohol withdrawal (21%, n=37) were the most
      common reasons recorded for admission to CDU in those who required STT. Median
      Alcohol Use Disorders Identification Test score was 25 and 112 patients (64%) had
      at least one Clinical Institute Withdrawal Assessment for Alcohol revised
      measurement >=10, triggering a dose of diazepam (20 mg). The median cumulative
      oral diazepam dose was 20 mg while 24 (15%) patients received a cumulative dose
      of 100 mg or more. Median time for STT was 12 hours (IQR=12, R=1-48). 3% (n=5) of
      patients required further general hospital admission and median LOS in CDU, was
      22 hours (IQR=20, R=1-168). CONCLUSION: STT is potentially feasible as a rapid
      and effective approach to managing alcohol withdrawal syndrome in the ED/CDU
      short-stay inpatient setting where patient LOS is generally less than 24 hours.

PMID- 30282631
TI  - Craving creativity: artists respond to addiction.

PMID- 30282632
TI  - Loss of CAMSAP3 promotes EMT via the modification of microtubule-Akt machinery.
AB  - Epithelial-to-mesenchymal transition (EMT) plays pivotal roles in a variety of
      biological processes, including cancer invasion. Although EMT involves
      alterations of cytoskeletal proteins such as microtubules, the role of
      microtubules in EMT is not fully understood. Microtubule dynamics are regulated
      by microtubule-binding proteins, and one such protein is CAMSAP3, which binds the
      minus-end of microtubules. Here, we show that CAMSAP3 is important to preserve
      the epithelial phenotypes in lung carcinoma cells. Deletion of CAMSAP3 in human
      lung carcinoma-derived cell lines showed that CAMSAP3-deficient cells acquired
      increased mesenchymal features, mostly at the transcriptional level. Analysis of
      the mechanisms underlying these changes demonstrated that tubulin acetylation was
      dramatically increased following CAMSAP3 removal, leading to the upregulation of
      Akt proteins (also known as protein kinase B proteins, hereafter Akt) activity,
      which is known to promote EMT. These findings suggest that CAMSAP3 functions to
      protect lung carcinoma cells against EMT by suppressing Akt activity via
      microtubule regulation and that CAMSAP3 loss promotes EMT in these cells.This
      article has an associated First Person interview with the first author of the
      paper.

PMID- 30282633
TI  - Thyroid hormone therapy does not improve symptoms in subclinical hypothyroidism,
      review finds.

PMID- 30282634
TI  - Cardiovascular disease and COPD: dangerous liaisons?
AB  - Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD)
      frequently occur together and their coexistence is associated with worse outcomes
      than either condition alone. Pathophysiological links between COPD and CVD
      include lung hyperinflation, systemic inflammation and COPD exacerbations. COPD
      treatments may produce beneficial cardiovascular (CV) effects, such as long
      acting bronchodilators, which are associated with improvements in arterial
      stiffness, pulmonary vasoconstriction, and cardiac function. However, data are
      limited regarding whether these translate into benefits in CV outcomes. Some
      studies have suggested that treatment with long-acting beta2-agonists and long
      acting muscarinic antagonists leads to an increase in the risk of CV events,
      particularly at treatment initiation, although the safety profile of these agents
      with prolonged use appears reassuring. Some CV medications may have a beneficial
      impact on COPD outcomes, but there have been concerns about beta-blocker use
      leading to bronchospasm in COPD, which may result in patients not receiving
      guideline-recommended treatment. However, there are few data suggesting harm with
      these agents and patients should not be denied beta-blockers if required. Clearer
      recommendations are necessary regarding the identification and management of
      comorbid CVD in patients with COPD in order to facilitate early intervention and
      appropriate treatment.

PMID- 30282636
TI  - Activin/Smad2 and Wnt/beta-catenin up-regulate HAS2 and ALDH3A2 to facilitate
      mesendoderm differentiation of human embryonic stem cells.
AB  - Activin and Wnt signaling are necessary and sufficient for mesendoderm (ME)
      differentiation of human embryonic stem cells (ESCs). In this study, we report
      that during ME differentiation induced by Activin and Wnt, Activin/Smad2 induces
      a decrease of the repressive histone modification of H3K27me3 by promoting the
      proteasome-dependent degradation of enhancer of zeste 2 polycomb (EZH2)
      repressive complex 2 subunit. As a result, recruitment of the forkhead protein
      FOXH1 on open chromatin regions integrates the signals of Activin/Smad2 and
      Wnt/beta-catenin to activate the expression of the ME genes including HAS2 and
      ALDH3A2 Consistently, H3K27me3 decrease is enriched on open chromatin around
      regulatory regions. Furthermore, knockdown of HAS2 or ALDH3A2 greatly attenuates
      ME differentiation. These findings unveil a pathway from extracellular signals to
      epigenetic modification-mediated gene activation during ME commitment.

PMID- 30282637
TI  - MicroRNA-451a in extracellular, blood-resident vesicles attenuates macrophage and
      dendritic cell responses to influenza whole-virus vaccine.
AB  - The innate immune system is important for the efficacy of vaccines, but excessive
      innate immune responses can cause adverse reactions after vaccination.
      Extracellular vesicles (EVs) are enriched in the blood and can deliver functional
      RNAs, such as microRNAs (miRNAs), to recipient cells, thereby mediating
      intercellular communication. However, the role of EVs in controlling the innate
      immune responses to vaccines has not been fully elucidated. Here, we found that
      miR-451a is abundant in human serum EVs and that its presence in blood
      circulating EVs affects the innate immune responses of macrophages and dendritic
      cells to inactivated whole-virus vaccines (WV) against influenza. miR-451a in
      human serum EVs was stable for a week in healthy subjects, and its levels
      gradually fluctuated over several months. miR-451a within serum EVs was
      internalized into serum-cultured macrophages and dendritic cells and reduced
      endogenous 14-3-3zeta protein levels and decreased the expression of type I IFN
      and interleukin 6 in response to WV stimulation. miR-451a levels in blood
      circulating EVs were positively correlated with intracellular miR-451a levels in
      mouse splenic CD11c+ cells and inversely correlated with the innate immune
      response to inactivated WV in vivo These findings suggest that miR-451a in
      circulating EVs is internalized into recipient cells in vivo and that this
      internalization results in an attenuation of the innate immune response to WV.
      Moreover, a microarray analysis identified several other miRNAs that affect the
      macrophage response to inactivated WV. Our results reveal that miRNAs in
      circulating EVs significantly modify the responses of macrophages and dendritic
      cells to inactivated WV.

PMID- 30282638
TI  - Advancing the science of discharges against medical advice: taking a deeper dive.

PMID- 30282635
TI  - Mini-GAGR, an intranasally applied polysaccharide, activates the neuronal Nrf2
      mediated antioxidant defense system.
AB  - Oxidative stress triggers and exacerbates neurodegeneration in Alzheimer's
      disease (AD). Various antioxidants reduce oxidative stress, but these agents have
      little efficacy due to poor blood-brain barrier (BBB) permeability. Additionally,
      single-modal antioxidants are easily overwhelmed by global oxidative stress.
      Activating nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) and its
      downstream antioxidant system are considered very effective for reducing global
      oxidative stress. Thus far, only a few BBB-permeable agents activate the Nrf2
      dependent antioxidant system. Here, we discovered a BBB-bypassing Nrf2-activating
      polysaccharide that may attenuate AD pathogenesis. Mini-GAGR, a 0.7-kDa cleavage
      product of low-acyl gellan gum, increased the levels and activities of Nrf2
      dependent antioxidant enzymes, decreased reactive oxygen species (ROS) under
      oxidative stress in mouse cortical neurons, and robustly protected mitochondria
      from oxidative insults. Moreover, mini-GAGR increased the nuclear localization
      and transcriptional activity of Nrf2 similarly to known Nrf2 activators.
      Mechanistically, mini-GAGR increased the dissociation of Nrf2 from its inhibitor,
      Kelch-like ECH-associated protein 1 (Keap1), and induced phosphorylation and
      nuclear translocation of Nrf2 in a protein kinase C (PKC)- and fibroblast growth
      factor receptor (FGFR1)-dependent manner. Finally, 20-day intranasal treatment of
      3xTg-AD mice with 100 nmol of mini-GAGR increased nuclear p-Nrf2 and growth
      associated protein 43 (GAP43) levels in hippocampal neurons, reduced p-tau and
      beta-amyloid (Abeta) peptide-stained neurons, and improved memory. The BBB
      bypassing Nrf2-activating polysaccharide reported here may be effective in
      reducing oxidative stress and neurodegeneration in AD.

PMID- 30282639
TI  - Effects of comprehensive cardiac rehabilitation on functional capacity in a
      middle-income country: a randomised controlled trial.
AB  - OBJECTIVE: Despite the growing epidemic of cardiovascular diseases in middle
      income countries, there is insufficient evidence about cardiac rehabilitation
      (CR) in these countries. Thus, the effects of comprehensive CR on functional
      capacity and risk factors were investigated in Brazil, to test the hypothesis
      that it results in better outcomes than exercise-only or no CR. METHODS: Single
      blinded, randomised controlled trial with three parallel arms: comprehensive CR
      (exercise+education) versus exercise-only CR versus wait-list control. Eligible
      coronary patients were randomised in blocks of four with 1:1:1 concealed
      allocation. Participants randomised to exercise-only CR received 36 exercise
      classes; comprehensive CR group also received 24 educational sessions. The
      primary outcome was incremental shuttle walk test (ISWT) distance; secondary
      outcomes were cardiovascular risk factors. All outcomes were assessed at baseline
      and 6 months later. Analysis of covariance was performed on the basis of
      intention-to-treat (ITT) and per-protocol. RESULTS: 115 (88.5%) patients were
      randomised; 93 (80.9%) were retained. There were improvements in ISWT distance
      from pretest to post-test with comprehensive (from 358.4+/-132.6 to 464.8+/-121.6
      m; mean change=106.4; p<0.001) and exercise-only (from 391.5+/-118.8 to 488.1+/
      106.3 m; mean change=96.5, p<0.001) CR, with significantly greater functional
      capacity with comprehensive CR versus control (ITT: mean difference=75.6+/-30.7
      m, 95% CI 1.4 to 150.2). There were also reductions in systolic blood pressure
      with comprehensive CR (ITT: reduction of 6.2+/-17.8 mm Hg, p=0.04). There were no
      significant differences for other outcomes. CONCLUSION: Results showed clinically
      significant improvements in functional capacity and blood pressure with CR, and
      significantly greater functional capacity with comprehensive CR compared with
      usual care. TRIAL REGISTRATION NUMBER: NCT02575976;Results.

PMID- 30282640
TI  - Global longitudinal strain, myocardial storage and hypertrophy in Fabry disease.
AB  - INTRODUCTION: Detecting early cardiac involvement in Fabry disease (FD) is
      important because therapy may alter disease progression. Cardiovascular magnetic
      resonance (CMR) can detect T1 lowering, representing myocardial sphingolipid
      storage. In many diseases, early mechanical dysfunction may be detected by
      abnormal global longitudinal strain (GLS). We explored the relationship of early
      mechanical dysfunction and sphingolipid deposition in FD. METHODS: An
      observational study of 221 FD and 77 healthy volunteers (HVs) who underwent CMR
      (LV volumes, mass, native T1, GLS, late gadolinium enhancement), ECG and blood
      biomarkers, as part of the prospective multicentre Fabry400 study. RESULTS: All
      FD had normal LV ejection fraction (EF 73%+/-8%). Mean indexed LV mass (LVMi) was
      89+/-39 g/m2 in FD and 55.6+/-10 g/m2 in HV. 102 (46%) FD participants had left
      ventricular hypertrophy (LVH). There was a negative correlation between GLS and
      native T1 in FD patients (r=-0.515, p<0.001). In FD patients without LVH (early
      disease), as native T1 reduced there was impairment in GLS (r=-0.285, p<0.002).
      In the total FD cohort, ECG abnormalities were associated with a significant
      impairment in GLS compared with those without ECG abnormalities (abnormal: 
      16.7+/-3.5 vs normal: -20.2+/-2.4, p<0.001). CONCLUSIONS: GLS in FD correlates
      with an increase in LVMi, storage and the presence of ECG abnormalities. In LVH
      negative FD (early disease), impairment in GLS is associated with a reduction in
      native T1, suggesting that mechanical dysfunction occurs before evidence of
      sphingolipid deposition (low T1). TRIAL REGISTRATION NUMBER: NCT03199001;
      Results.

PMID- 30282641
TI  - Seventy-six-year-old man with progressive dyspnoea.
AB  - CLINICAL INTRODUCTION: A 76-year-old man with 50 years of smoking history was
      diagnosed in 2012 with diffuse interstitial lung disease, with radiological data
      of usual interstitial pneumonia. He came to the emergency room presenting with
      progression of dyspnoea for 1 week, concomitant with loss of 5 kg of weight,
      anorexia and poor general condition. He had tachypnoea at rest (30 breaths/min),
      peripheral cyanosis, speech interfered by cough and breathlessness, baseline
      oxygen saturation 90%, heart rate 40 beats/min and blood pressure 130/70 mm Hg.
      Chest X-ray was performed and there was basal atelectasia of the right lung. ECG
      and urgent echocardiogram (transthoracic echocardiogram, TTE) were also performed
      (figure 1). heartjnl;heartjnl-2018-313779v1/F1F1F1Figure 1(A) ECG. (B) Long-axis
      parasternal view from the transthoracic echocardiogram (TTE). (C) Four-chamber
      view from the TTE. QUESTION: Which of the following best explains the patient's
      situation?Acute pulmonary embolismNon-ST elevation myocardial infarctionCardiac
      lymphomaCardiac myxomaMobitz type II AV block.

PMID- 30282642
TI  - Successful hematopoietic stem cell mobilization and apheresis collection using
      plerixafor alone in sickle cell patients.
AB  - Novel therapies for sickle cell disease (SCD) based on genetically engineered
      autologous hematopoietic stem and progenitor cells (HSPCs) are critically
      dependent on a safe and effective strategy for cell procurement. We sought to
      assess the safety and efficacy of plerixafor when used in transfused patients
      with SCD for HSC mobilization. Six adult patients with SCD were recruited to
      receive a single dose of plerixafor, tested at lower than standard (180 ug/kg)
      and standard (240 ug/kg) doses, followed by CD34+ cell monitoring in peripheral
      blood and apheresis collection. The procedures were safe and well-tolerated.
      Mobilization was successful, with higher peripheral CD34+ cell counts in the
      standard vs the low-dose group. Among our 6 donors, we improved apheresis cell
      collection results by using a deep collection interface and starting apheresis
      within 4 hours after plerixafor administration. In the subjects who received a
      single standard dose of plerixafor and followed the optimized collection
      protocol, yields of up to 24.5 * 106 CD34+ cells/kg were achieved. Interestingly,
      the collected CD34+ cells were enriched in immunophenotypically defined long-term
      HSCs and early progenitors. Thus, we demonstrate that plerixafor can be employed
      safely in patients with SCD to obtain sufficient HSCs for potential use in gene
      therapy.

PMID- 30282644
TI  - NHS will pay L20m compensation to teenager for brain injury.

PMID- 30282645
TI  - Impact of the NHS Health Check on inequalities in cardiovascular disease risk: a
      difference-in-differences matching analysis.
AB  - BACKGROUND: We assessed impacts of a large, nationwide cardiovascular disease
      (CVD) risk assessment and management programme on sociodemographic group
      inequalities in (1) early identification of hypertension, type 2 diabetes (T2D)
      and chronic kidney disease (CKD); and (2) management of global CVD risk among
      high-risk individuals. METHODS: We obtained retrospective electronic medical
      records from the Clinical Practice Research Datalink for a randomly selected
      sample of 138 788 patients aged 40-74 years without known CVD or diabetes, who
      were registered with 462 practices between 2009 and 2013. We estimated programme
      impact using a difference-in-differences matching analysis that compared changes
      in outcome over time between attendees and non-attendees. RESULTS: National
      Health Service Health Check attendance was 21.4% (29 672/138 788). A
      significantly greater number of hypertension and T2D incident cases were
      identified in men than women (eg, an additional 4.02%, 95% CI 3.65% to 4.39%, and
      2.08%, 1.81% to 2.35% cases of hypertension in men and women, respectively). A
      significantly greater number of T2D incident cases were identified among
      attendees living in the most deprived areas, but no differences were found for
      hypertension and CKD across socioeconomic groups. No major differences in CVD
      risk management were observed between sociodemographic subgroups (eg, programme
      impact on 10-year CVD risk score was -1.13%, -1.48% to -0.78% in male and -1.53%,
      -2.36% to -0.71% in female attendees). CONCLUSION: During 2009-2013, the
      programme had low attendance and small overall impacts on early identification of
      disease and risk management. The age, sex and socioeconomic subgroups appeared to
      have derived similar level of benefits, leaving existing inequalities unchanged.
      These findings highlight the importance of population-wide interventions to
      address inequalities in CVD outcomes.

PMID- 30282643
TI  - Cell-lineage level-targeted sequencing to identify acute myeloid leukemia with
      myelodysplasia-related changes.
AB  - Acute myeloid leukemia (AML) is a clonal myeloid neoplasm that typically arises
      de novo; however, some cases evolve from a preleukemic state, such as
      myelodysplastic syndrome (MDS). Such secondary AMLs and those with typical MDS
      related clinical features are known as AMLs with myelodysplasia-related changes
      (AML-MRC). Because patients with AML-MRC have poor prognosis, more accurate
      diagnostic approaches are required. In this study, we performed targeted
      sequencing of 54 genes in 3 cell populations (granulocyte, blast, and T-cell
      fractions) using samples from 13 patients with MDS, 16 patients with clinically
      diagnosed AML-MRC, 4 patients with suspected AML-MRC but clinically diagnosed as
      AML not otherwise specified (AML-NOS), and 11 patients with de novo AML. We found
      that overlapping mutations, defined as those shared at least by the blast and
      granulocyte fractions, were significantly enriched in patients with MDS and AML
      MRC, including those with suspected AML-MRC, indicating a substantial history of
      clonal hematopoiesis. In contrast, blast-specific nonoverlapping mutations were
      significantly enriched in patients with de novo AML. Furthermore, the presence of
      overlapping mutations, excluding DNMT3A, TET2, and ASXL1, effectively segregated
      patients with MDS and AML-MRC or suspected AML-MRC from patients with de novo
      AML. Additionally, the presence of >=3 mutations in the blast fraction was useful
      for distinguishing patients with AML-MRC from those with MDS. In conclusion, our
      approach is useful for classifying clinically diagnosable AML-MRC and identifying
      clinically diagnosed AML-NOS as latent AML-MRC. Additional prospective studies
      are needed to confirm the utility of this approach.

PMID- 30282646
TI  - Changes in workplace car parking and commute mode: a natural experimental study.
AB  - BACKGROUND: The use of private motor vehicles places a considerable burden on
      public health. Changes in workplace car parking policies may be effective in
      shifting behaviour. We use a natural experimental design to assess whether
      changes in policy were associated with differences in commute mode. METHODS: We
      used cohort data from participants working in Cambridge (2009-2012). Commuters
      reported their trips and travel modes to work over the last week, workplace car
      parking policy and socioeconomic, environmental and health characteristics.
      Changes in policy were defined between phases (1608 transition periods; 884
      participants). Using generalised estimating equations, we estimated associations
      between changes in parking policy and the proportion of trips that (i) were
      exclusively by motor vehicle, (ii) involved walking or cycling and (iii) involved
      public transport at follow-up. RESULTS: 25.1% of trips were made by motor
      vehicle, 54.6% involved walking or cycling and 11.7% involved public transport.
      The introduction of free or paid workplace parking was associated with higher
      proportions of motor vehicle trips (11.4%, 95% CI (6.4 to 16.3)) and lower
      proportions involving walking or cycling (-13.3%, 95% CI (-20.2 to -6.4)) and
      public transport (-5.8%, 95% CI (-10.6 to -0.9)) compared with those with no
      workplace parking. Restrictive changes in policy were associated with shifts in
      the expected direction but these were not statistically significant. CONCLUSION:
      Relaxation of parking policy was associated with higher proportions of trips made
      by motor vehicle. Further longitudinal and intervention research is required to
      assess generalisability of these findings .

PMID- 30282647
TI  - The socially mediated recovery of a fearful fish paired with periodically
      replaced calm models.
AB  - Social learning is an important mechanism for acquiring knowledge about
      environmental risk. However, little work has explored the learning of safety and
      how such learning outcomes are shaped by the social environment. Here, we exposed
      minnows, Pimephales promelas, to a high-risk environment to induce behavioural
      responses associated with fear (e.g. neophobia). We then used the presence of
      calm conspecific models (low-risk individuals) to weaken these responses. When
      observers (individuals from the high-risk environment) and models were paired
      consistently in a one-on-one setting, the observers showed no recovery (i.e. no
      weakening of the fear responses), and instead the models indirectly acquired
      those responses (i.e. a socially transmitted state of fear). However, observers
      paired with models that were periodically replaced with new calm models showed a
      significant recovery, and each new model showed diminished socially transmitted
      fear. We argue that our understanding of predation-related fear and social
      information transfer can prove fruitful in understanding problems with fear and
      stress across animal taxa, including among humans who experience post-traumatic
      stress and secondary trauma. Our findings indicate that the periodic replacement
      of models can promote fear recovery in observers and reduce socially transmitted
      fear in models.

PMID- 30282649
TI  - Spatial heterogeneity contributes more to portfolio effects than species
      variability in bottom-associated marine fishes.
AB  - Variance of community abundance will be reduced relative to its theoretical
      maximum whenever population densities fluctuate asynchronously. Fishing
      communities and mobile predators can switch among fish species and/or fishing
      locations with asynchronous dynamics, thereby buffering against variable resource
      densities (termed 'portfolio effects', PEs). However, whether variation among
      species or locations represent the dominant contributor to PE remains relatively
      unexplored. Here, we apply a spatio-temporal model to multidecadal time series
      (1982-2015) for 20 bottom-associated fishes in seven marine ecosystems. For each
      ecosystem, we compute the reduction in variance over time in total biomass
      relative to its theoretical maximum if species and locations were perfectly
      correlated (total PE). We also compute the reduction in variance due to
      asynchrony among species at each location (species PE) or the reduction due to
      asynchrony among locations for each species (spatial PE). We specifically compute
      total, species and spatial PE in 10-year moving windows to detect changes over
      time. Our analyses revealed that spatial PE are stronger than species PE in six
      of seven ecosystems, and that ecosystems where species PE is constant over time
      can exhibit shifts in locations that strongly contribute to PE. We therefore
      recommend that spatial and total PE be monitored as ecosystem indicators
      representing risk exposure for human and natural consumers.

PMID- 30282648
TI  - Molecular archaeoparasitology identifies cultural changes in the Medieval
      Hanseatic trading centre of Lubeck.
AB  - Throughout history, humans have been afflicted by parasitic worms, and eggs are
      readily detected in archaeological deposits. This study integrated
      parasitological and ancient DNA methods with a large sample set dating between
      Neolithic and Early Modern periods to explore the utility of molecular
      archaeoparasitology as a new approach to study the past. Molecular analyses
      provided unequivocal species-level parasite identification and revealed location
      specific epidemiological signatures. Faecal-oral transmitted nematodes (Ascaris
      lumbricoides and Trichuris trichiura) were ubiquitous across time and space. By
      contrast, high numbers of food-associated cestodes (Diphyllobothrium latum and
      Taenia saginata) were restricted to medieval Lubeck. The presence of these
      cestodes and changes in their prevalence at approximately 1300 CE indicate
      substantial alterations in diet or parasite availability. Trichuris trichiura ITS
      1 sequences grouped into two clades; one ubiquitous and one restricted to
      medieval Lubeck and Bristol. The high sequence diversity of T.tITS-1 detected in
      Lubeck is consistent with its importance as a Hanseatic trading centre.
      Collectively, these results introduce molecular archaeoparasitology as an
      artefact-independent source of historical evidence.

PMID- 30282650
TI  - Comparative demography elucidates the longevity of parasitic and symbiotic
      relationships.
AB  - Parasitic and symbiotic relationships govern vast nutrient and energy flows, yet
      controversy surrounds their longevity. Enduring relationships may engender
      parallel phylogenies among hosts and parasites, but so may ephemeral
      relationships when parasites colonize related hosts. An understanding of whether
      symbiont and host populations have grown and contracted in concert would be
      useful when considering the temporal durability of these relationships. Here, we
      devised methods to compare demographic histories derived from genomic data. We
      compared the historical growth of the agent of severe human malaria, Plasmodium
      falciparum, and its mosquito vector, Anopheles gambiae, to human and primate
      histories, thereby discerning long-term parallels and anthropogenic population
      explosions. The growth history of Trichinella spiralis, a zoonotic parasite
      disseminated by swine, proved regionally specific, paralleling distinctive growth
      histories for wild boar in Asia and Europe. Parallel histories were inferred for
      an anemone and its algal symbiont (Exaiptasia pallida and Symbiodinium minutum).
      Concerted growth in potatoes and the agent of potato blight (Solanum tuberosum
      and Phytophthora infestans) did not commence until the age of potato
      domestication. Through these examples, we illustrate the utility of comparative
      historical demography as a new exploratory tool by which to interrogate the
      origins and durability of myriad ecological relationships. To facilitate future
      use of this approach, we introduce a tool called C-PSMC to align and evaluate the
      similarity of demographic history curves.

PMID- 30282651
TI  - Carrying a selfish genetic element predicts increased migration propensity in
      free-living wild house mice.
AB  - Life is built on cooperation between genes, which makes it vulnerable to
      parasitism. Selfish genetic elements that exploit this cooperation can achieve
      large fitness gains by increasing their transmission relative to the rest of the
      genome. This leads to counter-adaptations that generate unique selection
      pressures on the selfish genetic element. This arms race is similar to host
      parasite coevolution, as some multi-host parasites alter the host's behaviour to
      increase the chance of transmission to the next host. Here, we ask if, similarly
      to these parasites, a selfish genetic element in house mice, the t haplotype,
      also manipulates host behaviour, specifically the host's migration propensity.
      Variants of the t that manipulate migration propensity could increase in fitness
      in a meta-population. We show that juvenile mice carrying the t haplotype were
      more likely to emigrate from and were more often found as migrants within a long
      term free-living house mouse population. This result may have applied relevance
      as the t has been proposed as a basis for artificial gene drive systems for use
      in population control.

PMID- 30282652
TI  - Female control over multiple matings increases the opportunity for postcopulatory
      sexual selection.
AB  - It is widely acknowledged that in most species sexual selection continues after
      mating. Although it is generally accepted that females play an important role in
      generating paternity biases (i.e. cryptic female choice, CFC), we lack a
      quantitative understanding of the relative importance of female-controlled
      processes in influencing variance in male reproductive fitness. Here, we address
      this question experimentally using the guppy Poecilia reticulata, a polyandrous
      fish in which pre- and postcopulatory sexual selection jointly determine male
      reproductive fitness. We used a paired design to quantify patterns of paternity
      for pairs of rival males across two mating contexts, one in which the female
      retained full control over double (natural) matings and one where sperm from the
      same two males were artificially inseminated into the female. We then compared
      the relative paternity share for a given pair of males across both contexts,
      enabling us to test the key prediction that patterns of paternity will depend on
      the extent to which females retain behavioural control over matings. As
      predicted, we found stronger paternity biases when females retained full control
      over mating compared with when artificial insemination (AI) was used.
      Concomitantly, we show that the opportunity for postcopulatory sexual selection
      (standardized variance in male reproductive success) was greater when females
      retained control over double matings compared with when AI was used. Finally, we
      show that the paternity success of individual males exhibited higher
      repeatability across successive brood cycles when females retained behavioural
      control of matings compared with when AI was used. Collectively, these findings
      underscore the critical role that females play in determining the outcome of
      sexual selection and to our knowledge provide the first experimental evidence
      that behaviourally moderated components of CFC increase the opportunity for
      sexual selection.

PMID- 30282653
TI  - Expression of a novel surfactant protein gene is associated with sites of
      extrapulmonary respiration in a lungless salamander.
AB  - Numerous physiological and morphological adaptations were achieved during the
      transition to lungless respiration that accompanied evolutionary lung loss in
      plethodontid salamanders, including those that enable efficient gas exchange
      across extrapulmonary tissue. However, the molecular basis of these adaptations
      is unknown. Here, we show that lungless salamanders express in the larval
      integument and the adult buccopharynx-principal sites of respiratory gas exchange
      in these species-a novel paralogue of the gene surfactant-associated protein C
      (SFTPC), which is a critical component of pulmonary surfactant expressed
      exclusively in the lung in other vertebrates. The paralogous gene appears to be
      found only in salamanders, but, similar to SFTPC, in lunged salamanders it is
      expressed only in the lung. This heterotopic gene expression, combined with
      predictions from structural modelling and respiratory tissue ultrastructure,
      suggests that lungless salamanders may produce pulmonary surfactant-like
      secretions outside the lungs and that the novel paralogue of SFTPC might
      facilitate extrapulmonary respiration in the absence of lungs. Heterotopic
      expression of the SFTPC paralogue may have contributed to the remarkable
      evolutionary radiation of lungless salamanders, which account for more than two
      thirds of urodele species alive today.

PMID- 30282654
TI  - Rhythmic motor behaviour influences perception of visual time.
AB  - Temporal processing is fundamental for an accurate synchronization between motor
      behaviour and sensory processing. Here, we investigate how motor timing during
      rhythmic tapping influences perception of visual time. Participants listen to a
      sequence of four auditory tones played at 1 Hz and continue the sequence (without
      auditory stimulation) by tapping four times with their finger. During finger
      tapping, they are presented with an empty visual interval and are asked to judge
      its length compared to a previously internalized interval of 150 ms. The visual
      temporal estimates show non-monotonic changes locked to the finger tapping:
      perceived time is maximally expanded at halftime between the two consecutive
      finger taps, and maximally compressed near tap onsets. Importantly, the temporal
      dynamics of the perceptual time distortion scales linearly with the timing of the
      motor tapping, with maximal expansion always being anchored to the centre of the
      inter-tap interval. These results reveal an intrinsic coupling between distortion
      of perceptual time and production of self-timed motor rhythms, suggesting the
      existence of a timing mechanism that keeps perception and action accurately
      synchronized.

PMID- 30282655
TI  - Delayed trait development and the convergent evolution of shell kinesis in
      turtles.
AB  - Understanding developmental processes is foundational to clarifying the
      mechanisms by which convergent evolution occurs. Here, we show how a key
      convergently evolving trait is slowly 'acquired' in growing turtles. Many
      functionally relevant traits emerge late in turtle ontogeny, owing to design
      constraints imposed by the shell. We investigated this trend by examining derived
      patterns of shell formation associated with the multiple (at least 8) origins of
      shell kinesis in small-bodied turtles. Using box turtles as a model, we
      demonstrate that the flexible hinge joint required for shell kinesis
      differentiates gradually and via extensive repatterning of shell tissue.
      Disproportionate changes in shell shape and size substantiate that this
      transformation is a delayed ontogenetic response (3-5 years post-hatching) to
      structural alterations that arise in embryogenesis. These findings exemplify that
      the translation of genotype to phenotype may reach far beyond embryonic life
      stages. Thus, the temporal scope for developmental origins of adaptive
      morphological change might be broader than generally understood. We propose that
      delayed trait differentiation via tissue repatterning might facilitate phenotypic
      diversification and innovation that otherwise would not arise due to
      developmental constraints.

PMID- 30282656
TI  - A non-coding region near Follistatin controls head colour polymorphism in the
      Gouldian finch.
AB  - Discrete colour morphs coexisting within a single population are common in
      nature. In a broad range of organisms, sympatric colour morphs often display
      major differences in other traits, including morphology, physiology or behaviour.
      Despite the repeated occurrence of this phenomenon, our understanding of the
      genetics that underlie multi-trait differences and the factors that promote the
      long-term maintenance of phenotypic variability within a freely interbreeding
      population are incomplete. Here, we investigated the genetic basis of red and
      black head colour in the Gouldian finch (Erythrura gouldiae), a classic
      polymorphic system in which naturally occurring colour morphs also display
      differences in aggressivity and reproductive success. We show that the candidate
      locus is a small (approx. 70 kb) non-coding region mapping to the Z chromosome
      near the Follistatin (FST) gene. Unlike recent findings in other systems where
      phenotypic morphs are explained by large inversions containing hundreds of genes
      (so-called supergenes), we did not identify any structural rearrangements between
      the two haplotypes using linked-read sequencing technology. Nucleotide divergence
      between the red and black alleles was high when compared to the remainder of the
      Z chromosome, consistent with their maintenance as balanced polymorphisms over
      several million years. Our results illustrate how pleiotropic phenotypes can
      arise from simple genetic variation, probably regulatory in nature.

PMID- 30282657
TI  - Adaptive periodicity in the infectivity of malaria gametocytes to mosquitoes.
AB  - Daily rhythms in behaviour, physiology and molecular processes are expected to
      enable organisms to appropriately schedule activities according to consequences
      of the daily rotation of the Earth. For parasites, this includes capitalizing on
      periodicity in transmission opportunities and for hosts/vectors, this may select
      for rhythms in immune defence. We examine rhythms in the density and infectivity
      of transmission forms (gametocytes) of rodent malaria parasites in the host's
      blood, parasite development inside mosquito vectors and potential for onwards
      transmission. Furthermore, we simultaneously test whether mosquitoes exhibit
      rhythms in susceptibility. We reveal that at night, gametocytes are twice as
      infective, despite being less numerous in the blood. Enhanced infectiousness at
      night interacts with mosquito rhythms to increase sporozoite burdens fourfold
      when mosquitoes feed during their rest phase. Thus, changes in mosquito biting
      time (owing to bed nets) may render gametocytes less infective, but this is
      compensated for by the greater mosquito susceptibility.

PMID- 30282658
TI  - Roles of glycosaminoglycans as regulators of ligand/receptor complexes.
AB  - Glycosaminoglycans (GAGs) play a widespread role in embryonic development, as
      deletion of enzymes that contribute to GAG synthesis lead to deficiencies in cell
      migration and tissue modelling. Despite the biochemical and structural
      characterization of individual protein/GAG interactions, there is no concept
      available that links the molecular mechanisms of GAG/protein engagements to
      tissue development. Here, we focus on the role of GAG polymers in mediating
      interactions between cell surface receptors and their ligands. We categorize
      several switches that lead to ligand activation, inhibition, selection and
      addition, based on recent structural studies of select receptor/ligand complexes.
      Based on these principles, we propose that individual GAG polymers may affect
      several receptor pathways in parallel, orchestrating a cellular response to an
      environmental cue. We believe that it is worthwhile to study the role of GAGs as
      molecular switches, as this may lead to novel drug candidates to target processes
      such as angiogenesis, neuroregeneration and tumour metastasis.

PMID- 30282659
TI  - Intracellular RNA-tracking methods.
AB  - RNA tracking allows researchers to visualize RNA molecules in cells and tissues,
      providing important spatio-temporal information regarding RNA dynamics and
      function. Methods such as fluorescent in situ hybridization (FISH) and molecular
      beacons rely on complementary oligonucleotides to label and view endogenous
      transcripts. Other methods create artificial chimeric transcripts coupled with
      bacteriophage-derived coat proteins (e.g. MS2, lambdaN) to tag molecules in live
      cells. In other approaches, endogenous RNAs are recognized by complementary RNAs
      complexed with noncatalytic Cas proteins. Each technique has its own set of
      strengths and limitations that must be considered when planning an experiment.
      Here, we discuss the mechanisms, advantages, and weaknesses of in situ
      hybridization, molecular beacons, MS2 tagging and Cas-derived systems, as well as
      how RNA tracking can be employed to study various aspects of molecular biology.

PMID- 30282662
TI  - Mind-body therapies: an intervention to reduce work-related stress in veterinary
      academia.
AB  - Studies investigating perceived stress and mindfulness awareness support mind
      body therapy (MBT) effectiveness in reducing stress and anxiety and, thus, has
      potential to decrease work-related stress. A pre/postexperimental design involved
      30 faculty and staff working at Ross University School of Veterinary Medicine,
      Saint Kitts and Nevis, who experienced a two-day MBT intervention programme. An
      additional 16 faculty and staff not involved in MBT who went about their daily
      work schedules served as contemporary controls. Demographics, Perceived Stress
      Scale 10 (PSS-10), Mindful Attention Awareness Scale (MAAS), 16 Personality
      Factor (16PF) Openness to Change subscale and saliva cortisol concentrations were
      analysed. Control participants reported significantly perceived less stress (PSS
      10: M=13; sd=1.4) than intervention participants (M=20; sd=6.6) during pretest.
      However, at post-test the intervention group reported a significant decrease in
      perceived stress (M=11; sd=6.0). MAAS pretest results indicated the intervention
      group displayed a lower average score (M=54; sd=15.3) than control participants
      (M=68; sd=2.0). Post-MAAS intervention scores showed improvements in mindfulness
      (M=63; sd=15.3). Correlations between the 16PF Openness to Change subscale and
      MAAS were r=0.03 and r=-0.17 for the intervention and control groups,
      respectively. Mean concentrations of saliva cortisol indicated a larger and
      significant decline in cortisol for the intervention group both during day 1
      (P=0.0001) and day 2 (P=0.0008). In conclusion, these preliminary results provide
      support that MBTs in veterinary academia can improve psychological and
      physiological aspects of personal wellbeing.

PMID- 30282660
TI  - Wnt signalling in the development of axon, dendrites and synapses.
AB  - Wnts are a highly conserved family of secreted glycoproteins that play essential
      roles in the morphogenesis and body patterning during the development of metazoan
      species. In recent years, mounting evidence has revealed important functions of
      Wnt signalling in diverse aspects of neural development, including neuronal
      polarization, guidance and branching of the axon and dendrites, as well as
      synapse formation and its structural remodelling. In contrast to Wnt signalling
      in cell proliferation and differentiation, which mostly acts through beta-catenin
      dependent pathways, Wnts engage a diverse array of non-transcriptional cascades
      in neuronal development, such as the planar cell polarity, cytoskeletal or
      calcium signalling pathways. In this review, we summarize recent advances in the
      mechanisms of Wnt signalling in the development of axon, dendrite and synapse
      formation.

PMID- 30282664
TI  - Safety and effectiveness of albuterol solutions with and without benzalkonium
      chloride when administered by continuous nebulization.
AB  - PURPOSE: The results of a study to determine if rates of poor response differ in
      patients receiving continuous nebulized albuterol (CNA) therapy with or without
      the preservative benzalkonium chloride are presented. METHODS: A retrospective
      analysis of the records of all patients who received CNA therapy at a large
      academic medical center from July 2015 to January 2016 was conducted. Data from
      patient evaluations performed before and after a change to benzalkonium chloride
      containing albuterol were collected. The primary outcome was the rate of poor
      patient response, defined as a composite endpoint. Secondary outcomes included
      duration of therapy, dosing requirements, and duration of supplemental oxygen
      therapy. RESULTS: There was no significant difference in rates of poor response
      between patients exposed (n = 80) and patients not exposed (n = 48) to
      benzalkonium chloride (16% and 17%, respectively; p = 0.95). The cohort not
      exposed to benzalkonium chloride had a median CNA duration of 7.0 hours, as
      compared with 10.5 hours for the cohort exposed to benzalkonium chloride, but
      this difference was not significant (p = 0.19). There were no significant
      differences between the benzalkonium chloride-exposed and nonexposed cohorts in
      the maximum dosing requirement (12.6 mg/hr versus 12.8 mg/hr, p = 0.89) or median
      duration of supplemental oxygen use (27.5 hours versus 16.5 hours, p = 0.77).
      CONCLUSION: A study of hospitalized patients receiving CNA detected no
      significant difference in the frequency of poor response to therapy between
      groups receiving benzalkonium chloride-free versus benzalkonium chloride
      containing albuterol products.

PMID- 30282663
TI  - Primary care collaborative practice in quality improvement: Description of an
      interprofessional curriculum.
AB  - PURPOSE: An innovative quality improvement (QI)-focused interprofessional
      training curriculum for pharmacy residents and other healthcare trainees is
      described. SUMMARY: Effective interprofessional collaboration and the ability to
      carry out QI initiatives are important skills for all healthcare trainees to
      develop when they are in training. To cultivate those skills, in 2011 a Veterans
      Affairs medical center in Idaho implemented a unique yearlong interprofessional
      curriculum for healthcare trainees, including postgraduate year 1 (PGY1) and
      postgraduate year 2 (PGY2) pharmacy residents, physician trainees in internal
      medicine, nurses, and psychologists. The curriculum has both didactic and
      experiential components. After attending a series of 1-hour workshops early in
      the academic year, trainees are assigned to interprofessional teams and work for
      the remainder of the year to complete QI projects. Over 100 trainees have
      participated in the interprofessional QI curriculum, with the majority of trainee
      projects based in the primary care setting. Pharmacy residents were involved in
      62% of the projects completed in the 6 academic years ending with the 2016-17
      year. CONCLUSION: Establishing an interprofessional QI curriculum allowed
      pharmacy residents in PGY1 and PGY2 programs to collaborate with other members of
      the healthcare team. Benefits include QI skills development, a greater
      understanding of QI initiatives at the institution, stronger relationships with
      other healthcare trainees and mentors, and improvements to patient care and
      safety and facility performance.

PMID- 30282665
TI  - Development of an operational productivity tool within a cancer treatment center
      pharmacy.
AB  - PURPOSE: The development and implementation of an operational productivity tool
      in an academic cancer treatment center are described. SUMMARY: Based on the
      increasing complexity of care delivery within the oncology setting, solutions
      were explored within Cleveland Clinic pharmacy's productivity model. Data were
      electronically captured based on orders processed through the outpatient oncology
      setting, including hazardous and nonhazardous medications. Based on current
      workflow, inpatient and outpatient orders were reviewed in productivity metrics.
      The metric defining the variability of the workload itself was weighted dispense
      type as it was the best representation of a mixed-skill workflow. After
      conducting workflow process mapping, discrete measurable steps were assessed and
      evaluated daily. Operational components of interest included pharmacist
      verification activities and technician compounding activities. Historical
      production data were sampled for assigning relative value units (RVUs) respective
      to time to normalize workload into a common unit (i.e., 1 hour) and to relate
      work demand in a highly variable setting. RVUs were assigned and delineated by
      cognitive and distributive activities for pharmacists and technicians,
      respectively. The Cleveland Clinic department of pharmacy developed a
      productivity tool to retrospectively measure workload involving time to review,
      verify, reconstitute, admix, and deliver chemotherapeutic agents. The weighting
      of each medication allowed for precise and meaningful evaluation of productivity.
      With RVUs assigned to 2 years of operational metrics, there now exists an
      opportunity to monitor performance trends within the cancer treatment center
      pharmacy. The data are readily retrievable within the electronic health record.
      CONCLUSION: The productivity data provided precise information to assess trends
      in operations within the pharmacy of an outpatient cancer treatment center.

PMID- 30282661
TI  - Into the breach: how cells cope with wounds.
AB  - Repair of wounds to individual cells is crucial for organisms to survive daily
      physiological or environmental stresses, as well as pathogen assaults, which
      disrupt the plasma membrane. Sensing wounds, resealing membranes, closing wounds
      and remodelling plasma membrane/cortical cytoskeleton are four major steps that
      are essential to return cells to their pre-wounded states. This process relies on
      dynamic changes of the membrane/cytoskeleton that are indispensable for carrying
      out the repairs within tens of minutes. Studies from different cell wound repair
      models over the last two decades have revealed that the molecular mechanisms of
      single cell wound repair are very diverse and dependent on wound type, size,
      and/or species. Interestingly, different repair models have been shown to use
      similar proteins to achieve the same end result, albeit sometimes by distinctive
      mechanisms. Recent studies using cutting edge microscopy and molecular techniques
      are shedding new light on the molecular mechanisms during cellular wound repair.
      Here, we describe what is currently known about the mechanisms underlying this
      repair process. In addition, we discuss how the study of cellular wound repair-a
      powerful and inducible model-can contribute to our understanding of other
      fundamental biological processes such as cytokinesis, cell migration, cancer
      metastasis and human diseases.

PMID- 30282666
TI  - Efficacy of JAK1/2 inhibition in the treatment of chilblain lupus due to TREX1
      deficiency.

PMID- 30282668
TI  - Management of antiphospholipid syndrome.
AB  - Antiphospholipid syndrome, also known as 'Hughes Syndrome', is an autoimmune
      disease characterised by a set of clinical manifestations, almost all of which
      are direct or indirect sequelae of a hypercoagulable state involving the venous,
      and to a lesser extent the arterial vasculature. The incidence and prevalence of
      antiphospholipid syndrome are estimated at approximately 5 de novo cases per 100
      000 per year and 40-50 cases per 100 000 individuals, respectively. The clinical
      spectrum of antiphospholipid syndrome involves haematological (thrombocytopaenia,
      venous thrombosis), obstetrical (recurrent pregnancy loss), neurological (stroke,
      transient ischaemic attack, migraine, seizures, cognitive dysfunction, chorea,
      transverse myelitis, multiple sclerosis), cardiovascular (cardiac valve disease),
      dermatological (livedo reticularis and racemosa, skin ulceration and necrosis),
      renal (glomerulonephritis, renal thrombotic microangiopathy) and orthopaedic
      (avascular necrosis of bones, non-traumatic fractures) manifestations, among
      others. In addition to the classical antiphospholipid antibodies, namely
      anticardiolipin antibodies and lupus anticoagulant, new autoantibodies and
      antibody complexes of different immunoglobulin subtypes (IgA, IgG, IgM) are now
      recognised as significant contributors to the pathogenesis of antiphospholipid
      syndrome. Anticoagulation remains the cornerstone in the management of
      antiphospholipid syndrome; nevertheless, new drugs and therapeutic strategies are
      being tested, and some have been found effective for the primary and secondary
      thromboprophylaxis in antiphospholipid syndrome.

PMID- 30282669
TI  - Response to: 'Aortic ulceration in a tocilizumab-treated patient with Takayasu
      arteritis' by Liebling et al.

PMID- 30282670
TI  - Etanercept in patients with inflammatory hand osteoarthritis (EHOA): a
      multicentre, randomised, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: Hand osteoarthritis is a prevalent disease with limited treatment
      options. Since joint inflammation is often present, we investigated tumour
      necrosis factor (TNF) as treatment target in patients with proven joint
      inflammation in a proof-of-concept study. METHODS: This 1-year, double-blind,
      randomised, multicentre trial (NTR1192) enrolled patients with symptomatic
      erosive inflammatory hand osteoarthritis. Patients flaring after non-steroidal
      anti-inflammatory drug washout were randomised to etanercept (24 weeks 50
      mg/week, thereafter 25  mg/week) or placebo. The primary outcome was Visual
      Analogue Scale (VAS) pain at 24 weeks. Secondary outcomes included clinical and
      imaging outcomes (radiographs scored using Ghent University Scoring System (GUSS,
      n=54) and MRIs (n=20)). RESULTS: Of 90 patients randomised to etanercept (n=45)
      or placebo (n=45), respectively, 12 and 10 discontinued prematurely. More
      patients on placebo discontinued due to inefficacy (6 vs 3), but fewer due to
      adverse effects (1 vs 6). The mean between-group difference (MD) in VAS pain was
      not statistically significantly different (-5.7 (95% CI -15.9 to 4.5), p=0.27 at
      24 weeks; - 8.5 (95% CI -18.6 to 1.6), p=0.10 at 1  year; favouring etanercept).
      In prespecified per-protocol analyses of completers with pain and inflammation at
      baseline (n=61), MD was -11.8 (95% CI -23.0 to -0.5) (p=0.04) at 1  year.
      Etanercept-treated joints showed more radiographic remodelling (delta GUSS: MD
      2.9 (95% CI 0.5 to 5.4), p=0.02) and less MRI bone marrow lesions (MD -0.22 (95%
      CI -0.35 to -0.09), p = 0.001); this was more pronounced in joints with baseline
      inflammation. CONCLUSION: Anti-TNF did not relieve pain effectively after 24
      weeks in erosive osteoarthritis. Small subgroup analyses showed a signal for
      effects on subchondral bone in actively inflamed joints, but future studies to
      confirm this are warranted.

PMID- 30282671
TI  - Somatic Mutations and Immune Alternation in Rectal Cancer Following Neoadjuvant
      Chemoradiotherapy.
AB  - Checkpoint blockade therapy triggers tumor-specific immune responses in a variety
      of cancer types. We presumed that rectal cancer patients could have become
      sensitive to immunotherapy after receiving neoadjuvant chemoradiotherapy (nCRT).
      In this study, we report immune alternation in post-nCRT patients compared with
      pretreatment conditions from gene-expression omnibus (GEO) data. Whole-exome
      sequencing of 14 locally advanced rectal cancer (LARC) patient samples showed
      that nCRT induced new mutations compared with the paired pretreatment biopsies,
      evidenced by appearance of a neoantigen landscape. An association was identified
      between mutation burden and enrichment of immune activation-related pathways.
      Animal experiment results further demonstrated that radiotherapy enhanced the
      efficacy of anti-PD-1. Mutation burden and the neoantigens of LARC patients were
      associated with response to nCRT. The mRNA expression profiling of 66
      pretreatment biopsy samples from LARC patients showed that immune activation
      related pathways were enriched in response to nCRT. PD-L1 expression was
      negatively correlated with disease-free survival in the CD8-low expression
      patient group who received nCRT in a cohort of 296 samples. Thus, nCRT was able
      to alter immune function in LARC patients, which may be associated with the
      appearance of neoantigens. Neoantigens could make rectal cancer patients
      potential candidates to receive checkpoint blockade immunotherapy, and mutation
      burden could be a useful biomarker to stratify patients into responding and
      nonresponding groups for immunotherapy. Cancer Immunol Res; 6(11); 1401-16.
      (c)2018 AACR.

PMID- 30282672
TI  - PD-L1 Mediates Dysfunction in Activated PD-1+ NK Cells in Head and Neck Cancer
      Patients.
AB  - Inhibitory immune-checkpoint receptors (ICRs), including programmed death 1 (PD
      1), have been characterized as exhaustion markers on T cells that infiltrate the
      tumor microenvironment (TME) of many cancer types, including head and neck cancer
      (HNC). However, expression and function of ICRs, including PD-1, on natural
      killer (NK) cells remains less defined. NK cells are innate immune effector cells
      that lyse epidermal growth factor receptor-overexpressing HNC cells via cetuximab
      mediated antibody-dependent cytotoxicity. Cetuximab is clinically effective but
      only in 10% to 15% of patients. Therefore, it is necessary to investigate how
      immunomodulation with cetuximab or PD-1 blockade might enhance NK cell responses
      in the TME and improve monoclonal antibody therapeutic efficacy. We observed that
      expression of PD-1 on NK cells marks an activated phenotype, which was suppressed
      only after binding programmed death ligand-1 (PD-L1). HNC patients who exhibit
      higher circulating PD-1+ NK cells associate with better clinical outcome, and
      these cells are enriched in the TME. Cetuximab-mediated NK cell activation
      increased PD-1 expression on NK cells in vitro, which was confirmed in vivo in a
      prospective neoadjuvant cetuximab trial. In contrast, PD-L1 ligation of PD-1+ NK
      cells diminished their activation status, whereas PD-1 blockade increased
      cetuximab-mediated NK cell activation and cytotoxicity, but only against HNC
      targets with high PD-L1 expression. Therefore, blocking the PD-1-PD-L1 axis may
      be a useful strategy to reverse immune evasion of HNC tumors with high PD-L1
      expression during cetuximab therapy by reversing NK cell dysfunction.

PMID- 30282673
TI  - Lysis Timer: a new sensitive tool to diagnose hyperfibrinolysis in liver
      transplantation.
AB  - AIMS: Diagnosis of hyperfibrinolysis in orthotopic liver transplantation (OLT)
      remains challenging. Euglobulin clot lysis time (ECLT) is not adapted to clinical
      situations. ROTEM is specific but seldom sensitive to hyperfibrinolysis. The
      Lysis Timer assesses 'Global Fibrinolytic Capacity' in citrated plasma (GFC/LT).
      GFC/LT associates reagents for in vitro triggering of the clot (thrombin and
      calcium) and its lysis (tissue-plasminogenactivator (t-PA)), turbidity signal
      acquisition by the Lysis Timer, and dedicated software converting the digital
      signal into an optical curve. A visual check of the curves was systematic to
      ascertain the lysis time values calculated by the software. The primary aim of
      this prospective observational study was to evaluate the ability of GFC/LT to
      recognise hyperfibrinolysis during OLT. The secondary aim was to compare its
      results with ROTEM maximum lysis (EXTEM ML) and with standard laboratory tests.
      METHODS: Thirty consecutive adult patients undergoing OLT were included
      (NCT03012633). Standard laboratory tests, ROTEM, GFC/LT, ECLT and fibrinolysis
      parameters were assayed at five sample times. RESULTS: GFC/LT was correlated with
      ECLT, plasmin activator inhibitor 1 antigen and activity and t-PA activity
      (r=0.490, 0.681, 0.643 and -0.359, respectively). Hyperfibrinolysis was defined
      as ECLT <=60 min. Receiver operating characteristic curve analysis showed that
      GFC/LT with a threshold of 31 min detected hyperfibrinolysis with a sensitivity
      of 0.88 (95% CI 0.73 to 0.96), a specificity of 0.68 (95% CI 0.56 to 0.78) and an
      area under the curve (AUC) of 0.85 (95% CI 0.74 to 0.94). EXTEM ML >12% did not
      detect hyperfibrinolysis (sensitivity 0.38 (95% CI 0.24 to 0.55), specificity
      0.95 (95% CI 0.86 to 0.99) and AUC 0.60 (95% CI 0.46 to 0.75)). CONCLUSIONS:
      GFC/LT recognised hyperfibrinolysis during OLT with a significant agreement with
      the other tests of fibrinolysis. TRIAL REGISTRATION NUMBER: NCT03012633.

PMID- 30282674
TI  - Physiological-based cord clamping in preterm infants using a new purpose-built
      resuscitation table: a feasibility study.
AB  - OBJECTIVE: Physiological-based cord clamping (PBCC) led to a more stable
      cardiovascular adaptation and better oxygenation in preterm lambs, but in preterm
      infants, this approach has been challenging. Our aim was to assess the
      feasibility of PBCC, including patterns of oxygen saturation (SpO2) and heart
      rate (HR) during stabilisation in preterm infants using a new purpose-built
      resuscitation table. DESIGN: Observational study. SETTING: Tertiary referral
      centre, Leiden University Medical Centre, The Netherlands. PATIENTS: Infants born
      below 35 weeks' gestational age. INTERVENTIONS: Infants were stabilised on a new
      purpose-built resuscitation table (Concord), provided with standard equipment
      needed for stabilisation. Cord clamping was performed when the infant was stable
      (HR >100 bpm, spontaneous breathing on continuous positive airway pressure with
      tidal volumes >4 mL/kg, SpO2 >=25th percentile and fraction of inspired oxygen
      (FiO2) <0.4). RESULTS: Thirty-seven preterm infants were included; mean (SD)
      gestational age of 30.9 (2.4) weeks, birth weight 1580 (519) g. PBCC was
      successful in 33 infants (89.2%) and resulted in median (IQR) cord clamping time
      of 4:23 (3:00-5:11) min after birth. There were no maternal or neonatal adverse
      events. In 26/37 infants, measurements were adequate for analysis. HR was 113 (81
      143) and 144 (129-155) bpm at 1 min and 5 min after birth. SpO2 levels were
      58%(49%-60%) and 91%(80%-96%)%), while median FiO2 given was 0.30 (0.30-0.31) and
      0.31 (0.25-0.97), respectively. CONCLUSION: PBCC in preterm infants using the
      Concord is feasible. HR remained stable, and SpO2 quickly increased with low
      levels of oxygen supply. TRIAL REGISTRATION NUMBER: NTR6095, results.

PMID- 30282675
TI  - Making doctors better.

PMID- 30282667
TI  - Kawasaki disease in infants 3 months of age and younger: a multicentre Spanish
      study.

PMID- 30282676
TI  - Can the completeness of radiological cancer staging reports be improved using
      proforma reporting? A prospective multicentre non-blinded interventional study
      across 21 centres in the UK.
AB  - OBJECTIVES: Following a diagnosis of cancer, the detailed assessment of
      prognostic stage by radiology is a crucial determinant of initial therapeutic
      strategy offered to patients. Pretherapeutic stage by imaging is known to be
      inconsistently documented. We tested whether the completeness of cancer staging
      radiology reports could be improved through a nationally introduced pilot of
      proforma-based reporting for a selection of six common cancers. DESIGN:
      Prospective interventional study comparing the completeness of radiology cancer
      staging reports before and after the introduction of proforma reporting. SETTING:
      Twenty-one UK National Health Service hospitals. PARTICIPANTS: 1283 cancer
      staging radiology reports were submitted. MAIN OUTCOME MEASURES: Radiology
      staging reports across the six cancers types were evaluated before and after the
      implementation of proforma-based reporting. Report completeness was assessed
      using scoring forms listing the presence or absence of predetermined key staging
      data. Qualitative data regarding proforma implementation and usefulness were
      collected from questionnaires provided to radiologists and end-users. RESULTS:
      Electronic proforma-based reporting was successfully implemented in 15 of the 21
      centres during the evaluation period. A total of 787 preproforma and 496
      postproforma staging reports were evaluated. In the preproforma group, only 48.7%
      (5586/11 470) of key staging items were present compared with 87.3% (6043/6920)
      in the postproforma group. Thus, the introduction of proforma reporting produced
      a 78% improvement in staging completeness . This increase was seen across all
      cancer types and centres. The majority of participants found proforma reporting
      improved cancer reporting quality for their clinical practice . CONCLUSION: The
      implementation of proforma reporting results in a significant improvement in the
      completeness of cancer staging reports. Proforma-based assessment of cancer stage
      enables objective comparisons of patient outcomes across centres. It should
      therefore become an auditable quality standard for cancer care.

PMID- 30282677
TI  - Safety and efficacy of self-administered inhaled loxapine (ADASUVE) in agitated
      patients outside the hospital setting: protocol for a phase IV, single-arm, open
      label trial.
AB  - INTRODUCTION: There is a need for fast-acting, non-injection antiagitation
      treatments that are well tolerated and can be used outside of healthcare
      facilities. In phase II/III trials, an inhaled formulation of loxapine
      (ADASUVE(r)), a well-established, first-generation antipsychotic agent, provided
      rapid control of mild to moderate agitation in the hospital setting. The present
      study was designed to investigate the safety and efficacy of inhaled loxapine
      when self-administered outside the hospital setting. METHODS AND ANALYSIS: This
      phase IV, multicentre, single-arm, open-label clinical trial is being conducted
      in five countries in Europe: Spain, Germany, Norway, Romania and Austria. The aim
      is to include approximately 500 patients with schizophrenia or bipolar disorder
      who previously received and responded well to inhaled loxapine in the hospital
      setting. Eligible patients will be followed up for 6 months from baseline. They
      will be given a 10 mg dose of inhaled loxapine to self-administer outside the
      hospital setting to treat an agitation episode, should one occur. Patients will
      also be given a short-acting beta-agonist bronchodilator for treatment of
      possible severe respiratory side effects. The primary endpoint is incidence of
      serious adverse events (AEs) and respiratory AEs of special interest related to
      use of inhaled loxapine outside the hospital setting. Secondary endpoints include
      incidence of other AEs, Clinical Global Impression-Improvement scores up to 2
      hours after self-administration of inhaled loxapine, time to improvement of
      agitation, patient satisfaction with treatment, treatment outcomes according to
      agitation severity and concordance between the patient (or a family
      member/caregiver) and the physician in scoring of agitation severity and the
      decision to self-administer inhaled loxapine. ETHICS AND DISSEMINATION: The
      protocol received ethics committee approval in the participating countries
      between January and August 2016. The results of this study will be disseminated
      through one or more scientific papers. TRIAL REGISTRATION NUMBER: EudraCT2015
      003331-36; NCT02525991; Pre-results.

PMID- 30282678
TI  - Limited implementation of the framework convention on tobacco control's tobacco
      tax provision: global comparison.
AB  - OBJECTIVE: To quantify changes in tobacco tax rates and cigarette affordability
      after countries ratified the WHO Framework Convention on Tobacco Control (FCTC)
      using with the WHO MPOWER standards. METHODS: We used logistic regression to
      assess the association of FCTC ratification with adoption of at least 50% and 75%
      (high) of retail price tobacco tax rates for the most sold brands in countries,
      accounting for years since ratification and other covariates. We also compared
      cigarette affordability in 2014 with 1999. RESULTS: By 2014, 44% of high-income
      countries had taxes above 75% of retail value compared with 18% in 1998/1999. In
      15 years, 69 countries increased the tobacco tax rate, 33 decreased it and one
      had the same tax rate. FCTC ratification was not associated with implementing
      high tobacco taxes. More fragile countries in terms of security, political,
      economic and social development were less likely to have at least 50% and 75%
      tobacco tax rates in 2014 compared with 1999. The higher the cigarette prices in
      1999 the less likely the countries were to have at least 75% tobacco tax rates in
      2014. However, cigarettes were less affordable in 2014 than in 1999 in countries
      that had ratified FCTC earlier. CONCLUSIONS: Despite widespread FCTC
      ratification, implementing higher tobacco taxes remains incomplete. Guidelines
      for FCTC Article 6 implementation should assign definite targets for tobacco
      taxes and for implementation of a tax escalator that gradually increases taxes to
      match rising income levels. Fragile countries are less likely to have high
      tobacco taxes and less affordable cigarettes. The tobacco control community
      should intensify efforts to help fragile countries improve performance in FCTC
      implementation both through strengthening their administrative and technical
      capacity and through supporting basic functions of government.

PMID- 30282679
TI  - Dynamics and Determinants of HPV Infection: The Michigan HPV and Oropharyngeal
      Cancer (M-HOC) Study.
AB  - INTRODUCTION: Human papillomavirus (HPV) is the primary cause of cervical and
      other anogenital cancers and is also associated with head and neck cancers.
      Incidence of HPV-related oropharyngeal squamous cell cancers (OPSCCs) is
      increasing, and HPV-related OPSCCs have surpassed cervical cancer as the most
      common HPV-related cancer in the USA. Given the multisite nature of HPV, there is
      strong interest in collecting data from both genital and oral sites, as well as
      associated data on social and sexual behaviours. The overarching goal of this
      study is to evaluate patterns of oral HPV infection incidence, clearance and
      persistence and their relationship to sexual behaviour history. METHODS AND
      ANALYSIS: Participants are recruited from two populations: college students at a
      large public university and general population from the surrounding area. At the
      first study visit, participants complete a detailed sexual history, health and
      behaviour questionnaire. Follow-up visits occur every 3-4 months over 3 years,
      when participants complete an abbreviated questionnaire. All participants provide
      a saliva sample at each visit, and eligible participants may provide a
      cervicovaginal self-swab. Genetic material isolated from specimens is tested for
      15 high-risk and 3 low-risk HPV types. Statistical analyses will examine outcome
      variables including HPV prevalence, incidence, persistence and clearance.
      Logistic regression models will be used to estimate odds ratios and 95%
      confidence intervals for associations between the outcomes of interest and
      demographic/behavioural variables collected in the questionnaires. The
      longitudinal HPV infection data and detailed sexual history data collected in the
      questionnaires will allow us to develop individual-based network models of HPV
      transmission and will be used to parameterise multiscale models of HPV-related
      OPSC carcinogenesis. ETHICS AND DISSEMINATION: This study has been approved by
      the University of Michigan Institutional Review Board. All participants are
      consented in person by trained study staff. Study results will be disseminated
      through peer-reviewed publications.

PMID- 30282680
TI  - Risk of behaviour suggestive of opioid abuse: a protocol for a systematic review
      of validated assessment tools.
AB  - INTRODUCTION: Opioid use patterns of individuals with non-cancer pain are
      influenced by the behavioural dynamics of the individual in managing and properly
      following the prescription. The use of assessment tools for measuring the risk of
      behaviour suggestive of opioid abuse is important for health professionals who
      provide care to individuals with non-cancer pain. The aim of the proposed review
      is to analyse the psychometric properties of tools for measuring the risk of
      behaviour suggestive of opioid abuse in adults with non-cancer pain. METHODS AND
      ANALYSIS: The review process will be based on the Preferred Reporting Items for
      Systematic Review and Meta-Analysis Protocols. The Consensus-Based Standards for
      the Selection of Health Measurement Instruments will be used to analyse the
      assessment tools. Two independent reviewers will perform the literature search
      and analysis procedures. Searches will be performed on PubMed, Web of Science,
      Cochrane, Scopus, and Cumulative Index to Nursing and Allied Health Literature
      databases, and the 'snowball' strategy will be employed. The inclusion criteria
      will be (1) validation studies, (2) assessment tools designed exclusively for
      measuring the risk of behaviour suggestive of opioid abuse and (3) assessment
      tools designed for evaluation of adults with chronic non-cancer pain. The titles
      and abstracts of the studies retrieved from the databases will be analysed for
      the preselection of articles, which will be submitted to a full-text analysis to
      define the final sample. Divergence of opinion between two reviewers will be
      resolved by consulting a third reviewer. ETHICS AND DISSEMINATION: The review
      will offer an overview of assessment tools available for measuring the risk of
      behaviour suggestive of opioid abuse, which is relevant to reducing the risk of
      deaths due to abusive consumption and for clinical management of adults with
      chronic non-cancer pain. PROSPERO REGISTRATION NUMBER: CRD42018081577.

PMID- 30282681
TI  - Association of Meniere's disease and retinal vascular calibre: a prospective
      observational study in China.
AB  - OBJECTIVE: It is believed that Meniere's disease (MD) is associated with vascular
      disorders, but few studies have reported the relationship between retinal
      vascular disorders and MD. We evaluated and compared the retinal vascular
      calibres in patients with MD with healthy subjects matched for age, sex and
      vascular risk factors using retinal photographs to explore the association
      between MD and retinal vascular calibre. STUDY DESIGN: A prospective study.
      SETTING: Tertiary referral centre. PARTICIPANTS: Sixty patients with MD and 62
      healthy subjects matched for age, sex and vascular risk factors were enrolled in
      this study. Twenty-four patients with MD had migraines, and 36 patients with MD
      did not have migraines. MAIN OUTCOME MEASURE: Retinal vascular calibres were
      calculated and compared not only between patients with MD and healthy subjects
      but also between subgroups of patients with MD. RESULTS: Compared with healthy
      subjects, patients with MD had a slightly larger retinal artery calibre (126.30+/
      10.45vs 119.61+/-15.86, p=0.006) and a higher retinal artery/vein ratio (0.79+/
      0.09vs 0.75+/-0.10, p=0.005). Among patients with MD, those with migraines had a
      larger retinal artery calibre (130.73+/-11.55vs 123.35+/-8.61, p=0.006) than
      those without migraines. Moreover, the presence of migraines and the high
      frequency of vertigo attacks appeared to increase the retinal artery calibre.
      CONCLUSIONS: Our study suggests that a relationship exists between retinal
      vascular calibre and MD. Although the pathophysiological relationship between
      migraine and MD remains unclear, the presence of migraine attacks may aggravate
      endolymphatic hydrops (EH) and accelerate the outflow of EH in patients with MD.
      More extensive studies are required to explore the association between retinal
      vascular calibre and MD.

PMID- 30282682
TI  - Reduced prevalence of small-for-gestational-age and preterm birth for women of
      low socioeconomic position: a population-based cohort study comparing antenatal
      midwifery and physician models of care.
AB  - OBJECTIVE: Our aim was to investigate if antenatal midwifery care was associated
      with lower odds of small-for-gestational-age (SGA) birth, preterm birth (PTB) or
      low birth weight (LBW) compared with general practitioner (GP) or obstetrician
      (OB) models of care for women of low socioeconomic position. SETTING: This
      population-level, retrospective cohort study used province-wide maternity,
      medical billing and demographic data from British Columbia, Canada. PARTICIPANTS:
      Our study included 57 872 pregnant women, with low socioeconomic position, who:
      were residents of British Columbia, Canada, carried a singleton fetus, had low to
      moderate medical/obstetric risk, delivered between 2005 and 2012 and received
      medical insurance premium assistance. PRIMARY AND SECONDARY OUTCOME MEASURES: We
      report rates, adjusted ORs (aOR), and 95% CIs for the primary outcome, SGA birth
      (<the 10th percentile), and secondary outcomes, PTB (<37 weeks' completed
      gestation) and LBW (<2500 g). RESULTS: Our sample included 4705 midwifery
      patients, 45 114 GP patients and 8053 OB patients. Odds of SGA birth were reduced
      for patients receiving antenatal midwifery versus GP (aOR 0.71, 95% CI 0.62 to
      0.82) or OB care (aOR 0.59, 95% CI 0.50 to 0.69). Odds of PTB were lower for
      antenatal midwifery versus GP (aOR 0.74, 95% CI 0.63 to 0.86) or OB patients (aOR
      0.53, 95% CI 0.45 to 0.62). Odds of LBW were reduced for midwifery versus GP (aOR
      0.66, 95% CI 0.53 to 0.82) or OB patients (aOR 0.43, 95% CI 0.34 to 0.54).
      CONCLUSION: Antenatal midwifery care in British Columbia, Canada, was associated
      with lower odds of SGA birth, PTB and LBW, for women of low socioeconomic
      position, compared with physician models of care. Results support the development
      of policy to ensure antenatal midwifery care is available and accessible for
      women of low socioeconomic position. Future research is needed to determine the
      underlying mechanisms linking midwifery care to better birth outcomes for women
      of low socioeconomic position.

PMID- 30282683
TI  - Getting the most out of intensive longitudinal data: a methodological review of
      workload-injury studies.
AB  - OBJECTIVES: To systematically identify and qualitatively review the statistical
      approaches used in prospective cohort studies of team sports that reported
      intensive longitudinal data (ILD) (>20 observations per athlete) and examined the
      relationship between athletic workloads and injuries. Since longitudinal research
      can be improved by aligning the (1) theoretical model, (2) temporal design and
      (3) statistical approach, we reviewed the statistical approaches used in these
      studies to evaluate how closely they aligned these three components. DESIGN:
      Methodological review. METHODS: After finding 6 systematic reviews and 1
      consensus statement in our systematic search, we extracted 34 original
      prospective cohort studies of team sports that reported ILD (>20 observations per
      athlete) and examined the relationship between athletic workloads and injuries.
      Using Professor Linda Collins' three-part framework of aligning the theoretical
      model, temporal design and statistical approach, we qualitatively assessed how
      well the statistical approaches aligned with the intensive longitudinal nature of
      the data, and with the underlying theoretical model. Finally, we discussed the
      implications of each statistical approach and provide recommendations for future
      research. RESULTS: Statistical methods such as correlations, t-tests and simple
      linear/logistic regression were commonly used. However, these methods did not
      adequately address the (1) themes of theoretical models underlying workloads and
      injury, nor the (2) temporal design challenges (ILD). Although time-to-event
      analyses (eg, Cox proportional hazards and frailty models) and multilevel
      modelling are better-suited for ILD, these were used in fewer than a 10% of the
      studies (n=3). CONCLUSIONS: Rapidly accelerating availability of ILD is the norm
      in many fields of healthcare delivery and thus health research. These data
      present an opportunity to better address research questions, especially when
      appropriate statistical analyses are chosen.

PMID- 30282684
TI  - Cognitive control and daily affect regulation in major depression and borderline
      personality disorder: protocol for an experimental ambulatory assessment study in
      Berlin, Germany.
AB  - INTRODUCTION: Affective disturbances and difficulty in affect regulation are core
      features of major depressive disorder (MDD) as well as borderline personality
      disorder (BPD). Whereas depressed individuals are characterised by affective
      inertia, individuals with BPD are characterised by affective instability. Both
      groups have been found to use more maladaptive affect regulation strategies than
      healthy controls. Surprisingly, however, there have been hardly any studies
      directly comparing these two disorders to disentangle shared and disorder
      specific deficits in affective dynamics and affect regulation.Furthermore,
      theoretical models link deficits in affect regulation to deficits in cognitive
      control functions. Given that individuals with MDD or BPD are both characterised
      by impairments in cognitive control, the present study will further examine the
      link between individual differences in cognitive control and disturbances in
      affect dynamics and regulation in the daily life of individuals with MDD or BPD.
      METHODS AND ANALYSES: We will use a smartphone application to assess negative and
      positive affect as well as affect regulation strategies at eight times a day for
      7 days. We will further employ four computerised tasks to assess two cognitive
      control functions, namely interference control and discarding irrelevant
      information from working memory. Our hypotheses will be tested using a
      multimethod approach. Power analyses determined a sample size of 159 (53 MDD, 53
      BPD, 53 controls) to detect medium effect sizes. ETHICS AND DISSEMINATION: Ethics
      approval has been obtained from the Freie Universitat Berlin. Data collection
      started in January 2017 and will last until the end of 2018. Results will be
      disseminated to relevant psychotherapeutic and patient communities in peer
      reviewed journals, and at scientific conferences.

PMID- 30282686
TI  - Acupuncture treatment for knee osteoarthritis with sensitive points: protocol for
      a multicentre randomised controlled trial.
AB  - INTRODUCTION: There is a lack of curative medical treatment for patients with
      knee osteoarthritis (KOA). Acupuncture represents an important alternative
      therapy. According to the theory of traditional Chinese medicine and preliminary
      clinical evidence, the patients' acupoints and tender points may become
      sensitised when the body suffers from a disease state; stimulation of such
      sensitive points could lead to a disease improvement. It is thus hypothesised
      that acupuncture at highly sensitised points on patients with KOA would achieve
      better treatment outcomes than acupuncture at low/non-sensitised points.
      Previously, we conducted a pilot trial to prove the feasibility of further
      investigation. METHODS AND ANALYSIS: A three-arm, parallel, multicentre
      randomised controlled trial of 666 patients will be conducted at four hospitals
      of China. Eligible patients with KOA who consent to participate will be randomly
      assigned to a high-sensitisation group (patients receive acupuncture treatment at
      high-sensitive points), a low/non-sensitisation group (patients receive
      acupuncture treatment at low/non-sensitive points) or a waiting-list group
      (patients receive standard acupuncture treatment after the study is concluded)
      via a central randomisation system using 1:1:1 ratio. The primary outcome is the
      change of Western Ontario and McMaster Universities Osteoarthritis Index total
      score from baseline to 16 weeks. Outcome assessors and data analysts will be
      blinded and participants will be asked not to reveal their allocation to
      assessors. The outcome analyses will be performed both on the intention-to-treat
      and per-protocol population. The primary analyses will test if acupuncture at
      highly sensitised points would achieve statistically better treatment outcomes
      than acupuncture at low/non-sensitised points and no acupuncture (ie, waiting
      list), respectively. A small number of prespecified subgroup analyses will be
      conducted. ETHICS AND DISSEMINATION: Ethics approval has been granted by the
      Bioethics Subcommittee of West China Hospital, Sichuan University: 2017 (Number
      228). Results will be expected to be published in peer-reviewed journals. TRIAL
      REGISTRATION NUMBER: NCT03299439.

PMID- 30282687
TI  - Opportunistic HPV vaccination at age 16-23 and cervical screening attendance in
      Sweden: a national register-based cohort study.
AB  - OBJECTIVES: To investigate whether cervical screening attendance differs between
      human papillomavirus (HPV)-vaccinated and unvaccinated women and to investigate
      potential underlying socioeconomic factors. DESIGN: Prospective cohort using
      registry linkage of vaccinations, screening invitations, screening attendance and
      socioeconomic covariates. SETTING: Swedish national HPV vaccination and cervical
      screening programmes. PARTICIPANTS: All Swedish women born between 1988 and 1991
      and invited to screening (n=261 434). OUTCOME MEASURES: All participants were
      followed for up to 3 years. Screening attendance was compared between HPV
      vaccinated and unvaccinated women. HR and 95% CI were estimated using Cox
      regression. RESULTS: Vaccination age averaged 18.1 years and the coverage for>=1
      dose was 13.5%. In HPV-vaccinated women (n=35 460), screening attendance was
      higher than in unvaccinated women (n=225 974) (74%vs69%, p<0.001). The crude HR
      of attendance in HPV-vaccinated women was 1.32 (95% CI 1.30 to 1.34). A positive
      association remained after adjustment for education, income and migration history
      (HR=1.10, 95% CI 1.09 to 1.12). CONCLUSION: HPV-vaccinated women were more likely
      to attend screening than unvaccinated women. Yet, the question needs to be
      reassessed in routinely vaccinated cohorts, since the vaccinated women included
      here represent a selected group and may be prone to more health-conscious habits.

PMID- 30282685
TI  - Protocol for the Lactoferrin Infant Feeding Trial (LIFT): a randomised trial of
      adding lactoferrin to the feeds of very-low birthweight babies prior to hospital
      discharge.
AB  - INTRODUCTION: Very-low birthweight (VLBW, <1500 g) infants comprise about 1%-1.4%
      of all births in high-income countries. Every year, about 3000 VLBW babies in
      Australia and New Zealand receive intensive care. Many die or else survive with
      severe brain injury, retinopathy, late-onset sepsis or necrotising enterocolitis
      (NEC), each of which carries substantial risk of disability. METHODS AND
      ANALYSIS: This trial tests whether adding bovine lactoferrin (bLF) to feeds in
      VLBW infants improves (1) survival to hospital discharge free from brain injury,
      late-onset sepsis, NEC and treated retinopathy of prematurity (primary composite
      end point); (2) each component of the primary composite end point and (3) time to
      reach full enteral feeds, number of blood transfusions, chronic lung disease and
      length of hospital stay. It includes a cost-effectiveness analysis of bLF in
      improving survival free from major morbidity, and evaluates the effect of bLF on
      survival and developmental outcomes at 24 to 36 months corrected gestational
      age.This is a multicentre, two-arm, randomised trial comparing the treatment
      group receiving bLF added to breast milk or formula milk daily (up to 250
      mg/kg/day bLF) versus the control group receiving no bLF supplementation. The
      intervention is administered until 34 completed weeks corrected gestation or for
      2 weeks, whichever is longer, or until discharge home, if earlier. The target
      sample size of 1500 participants yields 85% power, at the two-sided 5% level
      significance, to detect a difference in proportions meeting the primary outcome
      assuming the true probability is 74% in controls and 80.5% in the bLF group.
      ETHICS AND DISSEMINATION: This protocol was approved by Northern Sydney Local
      Human Research Ethics Committee in January 2017 (Version 2.0, Reference 1003
      118M) and other relevant ethics committees. The findings of the trial will be
      disseminated through peer-reviewed journals and conference presentations. TRIAL
      REGISTRATION NUMBER: ACTRN12611000247976; Pre-results.

PMID- 30282688
TI  - Randomised controlled trial of the Limit of Detection of Troponin and ECG
      Discharge (LoDED) strategy versus usual care in adult patients with chest pain
      attending the emergency department: study protocol.
AB  - INTRODUCTION: Observational data suggest a single high-sensitivity troponin blood
      test taken at emergency department (ED) presentation could be used to rule out
      major adverse cardiac events (MACE) in 10%-60% of ED patients with chest pain.
      This is done using an 'undetectable' cut-off (the Limit of Detection: LoD). We
      combined the LoD cut-off with ECG findings to create the LoDED strategy. We aim
      to establish whether the LoDED strategy works under real-life conditions, when
      compared with existing strategies, in a way that is cost-effective and acceptable
      to patients. METHODS AND ANALYSIS: This is a parallel-group pragmatic randomised
      controlled trial across UK EDs. Adults presenting to ED with suspected cardiac
      chest pain will be randomised 1:1. Existing rule-out strategies in current use
      across study centres, using serial high-sensitivity troponin testing, will be
      compared with the LoDED strategy. The primary outcome is successful early
      discharge (discharge from hospital within 4 hours of arrival) without MACE
      occurring within 30 days. Secondary outcomes include initial length of hospital
      stay; comparative costs; patient satisfaction and acceptability to patients. To
      detect a 9% difference between the early discharge rates (assuming an 8% rate in
      the standard care group) with 90% power, 594 patients need to be recruited,
      assuming a 95% follow-up rate. ETHICS AND DISSEMINATION: The study has been
      approved by the Frenchay Research Ethics Committee (reference 18/SW/0038).
      Results will be published in an international peer-reviewed journal. Lay
      summaries will be made available to patients. TRIAL REGISTRATION NUMBER:
      ISRCTN86184521; Pre-results.

PMID- 30282689
TI  - Effect of psychosocial work factors on the risk of certified absences from work
      for a diagnosed mental health problem: a protocol of a systematic review and meta
      analysis of prospective studies.
AB  - INTRODUCTION: Mental health problems (MHPs) are frequent and disabling and are
      the first or second leading cause of certified sickness absences from work in
      industrialised countries. They are generally long lasting and generate a
      considerable human and socioeconomic burden. The deleterious effect of adverse
      psychosocial work factors on MHP has been documented. However, the evidence
      regarding the effect of these factors on absences from work for an MHP has not
      been synthesised since 2007. The proposed systematic review aims to synthesise
      the effect of adverse psychosocial work factors from three validated theoretical
      models (the demand-control-support, effort-reward-imbalance and organisational
      justice models) on the risk of certified absences from work for diagnosed MHP
      among workers. METHOD AND ANALYSIS: A systematic search strategy will be
      conducted in seven databases: Medline, Embase, CINAHL, Web of Science, PsycInfo,
      Sociological abstracts and IBSS. Following Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses recommendations, a multistep screening
      process by independent reviewers will lead to study selection. The search
      strategy was first run in 16 January 2017 and will be updated in October 2018.
      Only quantitative, prospective studies evaluating the effect of at least one
      psychosocial work factor from the validated theoretical models on certified
      absence from work for a diagnosed MHP will be considered for inclusion. Extracted
      data will be used for quantitative and qualitative evidence synthesis as well as
      to assess risk of bias and methodological quality. Meta-estimates will be
      provided for high-quality studies and by each psychosocial work factor, after
      considering homogeneity and number of studies. ETHICS AND DISSEMINATION: As this
      study will be based only on published studies, ethics approval is not required.
      Given that psychosocial works factors are frequent and modifiable, the results of
      this systematic review may provide evidence to support prevention strategies that
      can help to reduce the human social and economic burden associated with medically
      certified absences from work for an MHP. PROSPERO REGISTRATION NUMBER:
      CRD42018091632.

PMID- 30282691
TI  - Generation of evidence should be tailored to individuals.

PMID- 30282690
TI  - Correction: Effect of iron and zinc-biofortified pearl millet consumption on
      growth and immune competence in children aged 12-18 months in India: study
      protocol for a randomised controlled trial.

PMID- 30282692
TI  - GSK will resume paying doctors to promote its drugs after policy U turn.

PMID- 30282694
TI  - An optical nanoreporter of endolysosomal lipid accumulation reveals enduring
      effects of diet on hepatic macrophages in vivo.
AB  - The abnormal accumulation of lipids within the endolysosomal lumen occurs in many
      conditions, including lysosomal storage disorders, atherosclerosis, nonalcoholic
      fatty liver disease (NAFLD), and drug-induced phospholipidosis. Current methods
      cannot monitor endolysosomal lipid content in vivo, hindering preclinical drug
      development and research into the mechanisms linking endolysosomal lipid
      accumulation to disease progression. We developed a single-walled carbon nanotube
      based optical reporter that noninvasively measures endolysosomal lipid
      accumulation via bandgap modulation of its intrinsic near-infrared emission. The
      reporter detected lipid accumulation in Niemann-Pick disease, atherosclerosis,
      and NAFLD models in vivo. By applying the reporter to the study of NAFLD, we
      found that elevated lipid quantities in hepatic macrophages caused by a high-fat
      diet persist long after reverting to a normal diet. The reporter dynamically
      monitored endolysosomal lipid accumulation in vivo over time scales ranging from
      minutes to weeks, indicating its potential to accelerate preclinical research and
      drug development processes.

PMID- 30282693
TI  - p95HER2-T cell bispecific antibody for breast cancer treatment.
AB  - T cell bispecific antibodies (TCBs) are engineered molecules that include, within
      a single entity, binding sites to the T cell receptor and to tumor-associated or
      tumor-specific antigens. The receptor tyrosine kinase HER2 is a tumor-associated
      antigen in ~25% of breast cancers. TCBs targeting HER2 may result in severe
      toxicities, likely due to the expression of HER2 in normal epithelia. About 40%
      of HER2-positive tumors express p95HER2, a carboxyl-terminal fragment of HER2.
      Using specific antibodies, here, we show that p95HER2 is not expressed in normal
      tissues. We describe the development of p95HER2-TCB and show that it has a potent
      antitumor effect on p95HER2-expressing breast primary cancers and brain lesions.
      In contrast with a TCB targeting HER2, p95HER2-TCB has no effect on
      nontransformed cells that do not overexpress HER2. These data pave the way for
      the safe treatment of a subgroup of HER2-positive tumors by targeting a tumor
      specific antigen.

PMID- 30282695
TI  - Huntingtin suppression restores cognitive function in a mouse model of
      Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      caused by a mutation in the huntingtin (HTT) protein, resulting in acquisition of
      toxic functions. Previous studies have shown that lowering mutant HTT has the
      potential to be broadly beneficial. We previously identified HTT single
      nucleotide polymorphisms (SNPs) tightly linked to the HD mutation and developed
      antisense oligonucleotides (ASOs) targeting HD-SNPs that selectively suppress
      mutant HTT. We tested allele-specific ASOs in a mouse model of HD. Both early and
      late treatment reduced cognitive and behavioral impairments in mice. To determine
      the translational potential of the treatment, we examined the effect of ASO
      administration on HTT brain expression in nonhuman primates. The treatment
      induced robust HTT suppression throughout the cortex and limbic system, areas
      implicated in cognition and psychiatric function. The results suggest that ASOs
      specifically targeting mutated HTT might have therapeutic effects on HD-mediated
      cognitive impairments.

PMID- 30282697
TI  - Regulating 3D-printed medical products.
AB  - Additive manufacturing [also known as three-dimensional (3D) printing] is the
      layer-wise deposition of material to produce a 3D object. This rapidly emerging
      technology has the potential to produce new medical products with unprecedented
      structural and functional designs. Here, we describe the U.S. regulatory
      landscape of additive manufactured (3D-printed) medical devices and biologics and
      highlight key challenges and considerations.

PMID- 30282696
TI  - Anti-alpha4beta7 therapy targets lymphoid aggregates in the gastrointestinal
      tract of HIV-1-infected individuals.
AB  - Gut homing CD4+ T cells expressing the integrin alpha4beta7 are early viral
      targets and contribute to HIV-1 pathogenesis, likely by seeding the
      gastrointestinal (GI) tract with HIV. Although simianized anti-alpha4beta7
      monoclonal antibodies have shown promise in preventing or attenuating the disease
      course of simian immunodeficiency virus in nonhuman primate studies, the
      mechanisms of drug action remain elusive. We present a cohort of individuals with
      mild inflammatory bowel disease and concomitant HIV-1 infection receiving anti
      alpha4beta7 treatment. By sampling the immune inductive and effector sites of the
      GI tract, we have discovered that anti-alpha4beta7 therapy led to a significant
      and unexpected attenuation of lymphoid aggregates, most notably in the terminal
      ileum. Given that lymphoid aggregates serve as important sanctuary sites for
      maintaining viral reservoirs, their attrition by anti-alpha4beta7 therapy has
      important implications for HIV-1 therapeutics and eradication efforts and defines
      a rational basis for the use of anti-alpha4beta7 therapy in HIV-1 infection.

PMID- 30282698
TI  - GABAA receptor availability is not altered in adults with autism spectrum
      disorder or in mouse models.
AB  - Preliminary studies have suggested that gamma-aminobutyric acid type A (GABAA)
      receptors, and potentially the GABAA alpha5 subtype, are deficient in autism
      spectrum disorder (ASD). However, prior studies have been confounded by the
      effects of medications, and these studies did not compare findings across
      different species. We measured both total GABAA and GABAA alpha5 receptor
      availability in two positron emission tomography imaging studies. We used the
      tracer [11C]flumazenil in 15 adults with ASD and in 15 control individuals
      without ASD and the tracer [11C]Ro15-4513 in 12 adults with ASD and in 16 control
      individuals without ASD. All participants were free of medications. We also
      performed autoradiography, using the same tracers, in three mouse models of ASD:
      the Cntnap2 knockout mouse, the Shank3 knockout mouse, and mice carrying a
      16p11.2 deletion. We found no differences in GABAA receptor or GABAA alpha5
      subunit availability in any brain region of adults with ASD compared to those
      without ASD. There were no differences in GABAA receptor or GABAA alpha5 subunit
      availability in any of the three mouse models. However, adults with ASD did
      display altered performance on a GABA-sensitive perceptual task. Our data suggest
      that GABAA receptor availability may be normal in adults with ASD, although GABA
      signaling may be functionally impaired.

PMID- 30282701
TI  - Correction to "Ketamine and Ketamine Metabolite Pharmacology: Insights into
      Therapeutic Mechanisms".

PMID- 30282700
TI  - Advances in the Treatment of Hemophilia: Implications for Laboratory Testing.
AB  - BACKGROUND: Until recently, clinical laboratories have monitored hemophilia
      treatment by measuring coagulation factors before/after infusion of human-derived
      or recombinant factors. Substantial changes are expected in the near future based
      on new therapeutic approaches that have been or are being developed. CONTENT:
      Hemophilia treatment includes replacement therapy with human-derived/recombinant
      factors or treatment with bypassing agents for patients without or with
      inhibitors, respectively. Accordingly, laboratory methods for monitoring include
      one-stage clotting or chromogenic assays meant to measure either factor VIII/IX
      or global coagulation tests to measure the effect of bypassing agents. Recently,
      modified long-acting coagulation factors have been introduced for which
      discrepant results may be expected when measurement is performed with one-stage
      clotting or chromogenic assays. Currently, novel drugs not based on coagulation
      factors are under development and are being tested in clinical studies. These
      drugs do require new methods and therefore laboratory evaluation of hemophilia
      will undergo dramatic changes in the near future. SUMMARY: From the analysis of
      the current practice and literature, we draw the following conclusions: (a)
      Thrombin generation or thromboelastometry are the logical candidate assays to
      monitor bypassing agents. (b) Considerable differences are expected when
      measuring modified long-acting coagulation factors, depending on whether one
      stage or chromogenic assays are used. Although no definitive conclusions can
      presently be drawn, chromogenic assays are probably more suitable than one-stage
      clotting. (c) Novel drugs not based on coagulation factors such as emicizumab,
      fitusiran, or concizumab that are entering the market do require alternative
      methods that are not yet well established.

PMID- 30282699
TI  - Impact of Gastric Banding Versus Metformin on beta-Cell Function in Adults With
      Impaired Glucose Tolerance or Mild Type 2 Diabetes.
AB  - OBJECTIVE: Type 2 diabetes (T2D) results from progressive loss of beta-cell
      function. The BetaFat study compared gastric banding and metformin for their
      impact on beta-cell function in adults with moderate obesity and impaired glucose
      tolerance (IGT) or recently diagnosed, mild T2D. RESEARCH DESIGN AND METHODS:
      Eighty-eight people aged 21-65 years, BMI 30-40 kg/m2, with IGT or diabetes known
      for <1 year, were randomized to gastric banding or metformin for 2 years.
      Hyperglycemic clamps (11.1 mmol/L) followed by arginine injection at maximally
      potentiating glycemia (>25 mmol/L) were performed at baseline, 12 months, and 24
      months to measure steady-state C-peptide (SSCP) and acute C-peptide response to
      arginine at maximum glycemic potentiation (ACPRmax) and insulin sensitivity
      (M/I). RESULTS: At 24 months, the band group lost 10.7 kg; the metformin group
      lost 1.7 kg (P < 0.01). Insulin sensitivity increased 45% in the band group and
      25% in the metformin group (P = 0.30 between groups). SSCP adjusted for insulin
      sensitivity fell slightly but not significantly in each group (P = 0.34 between
      groups). ACPRmax adjusted for insulin sensitivity fell significantly in the
      metformin group (P = 0.002) but not in the band group (P = 0.25 between groups).
      HbA1c fell at 12 and 24 months in the band group (P < 0.004) but only at 12
      months (P < 0.01) in the metformin group (P > 0.14 between groups). Normoglycemia
      was present in 22% and 15% of band and metformin groups, respectively, at 24
      months (P = 0.66 between groups). CONCLUSIONS: Gastric banding and metformin had
      similar effects to preserve beta-cell function and stabilize or improve glycemia
      over a 2-year period in moderately obese adults with IGT or recently diagnosed,
      mild T2D.

PMID- 30282702
TI  - Thomas Breuer and colleagues at GlaxoSmithKline respond to Peter Doshi.

PMID- 30282703
TI  - Collaboration between academics and industry in clinical trials: cross sectional
      study of publications and survey of lead academic authors.
AB  - OBJECTIVES: To determine the role of academic authors, funders, and contract
      research organisations in industry funded trials of vaccines, drugs, and devices
      and to determine lead academic authors' experiences with industry funder
      collaborations. DESIGN: Cross sectional analysis of trial publications and survey
      of lead academic authors. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: The most
      recent 200 phase III and IV trials of vaccines, drugs, and devices with full
      industry funding, at least one academic author, published in one of the top seven
      high impact general medical journals (New England Journal of Medicine, Lancet,
      JAMA, BMJ, Annals of Internal Medicine, JAMA Internal Medicine, and PLoS
      Medicine). RESULTS: Employees of industry funders co-authored 173 (87%) of
      publications; 183 (92%) trials reported involvement of funders in design, and 167
      (84%) reported involvement of academic authors. Data analysis involved the funder
      in 146 (73%) trials and the academic authors in 79 (40%). Trial reporting
      involved the funder in 173 (87%) trials and academic authors in 197 (99%).
      Contract research organisations were involved in the reporting of 123 (62%)
      trials.Eighty (40%) of 200 lead academic authors responded to the survey. Twenty
      nine (33%) of the 80 responders reported that academics had final say on the
      design. Ten responders described involvement of an unnamed funder and/or contract
      research organisation employee in the data analysis and/or reporting. Most
      academic authors found the collaboration with industry funder beneficial, but 3
      (4%) experienced delay in publication due to the industry funder and 9 (11%)
      reported disagreements with the industry funder, mostly concerning trial design
      and reporting. CONCLUSIONS: Industry employees and academic authors are involved
      in the design, conduct, and reporting of most industry funded trials in high
      impact journals. However, data analysis is often conducted without academic
      involvement. Academics view the collaboration as beneficial, but some report loss
      of academic freedom.

PMID- 30282704
TI  - Dynamin Is Required for Efficient Cytomegalovirus Maturation and Envelopment.
AB  - Cytomegalovirus secondary envelopment occurs in a virus-induced cytoplasmic
      assembly compartment (vAC) generated via a drastic reorganization of the
      membranes of the secretory and endocytic systems. Dynamin is a eukaryotic GTPase
      that is implicated in membrane remodeling and endocytic membrane fission events;
      however, the role of dynamin in cellular trafficking of viruses beyond virus
      entry is only partially understood. Mouse embryonic fibroblasts (MEF) engineered
      to excise all three isoforms of dynamin were infected with mouse cytomegalovirus
      (MCMV-K181). Immediate-early (IE1; m123) viral protein was detected in these
      triple dynamin knockout (TKO) cells, as well as in mock-induced parental MEF, at
      early times postinfection, although levels were reduced in TKO cells, indicating
      that virus entry was affected but not eliminated. Levels of IE1 protein and
      another viral early protein (m04) were normalized by 48 h postinfection; however,
      late protein (m55; gB) expression was reduced in infected TKO cells compared to
      parental MEF. Ultrastructural analysis revealed intact stages of nuclear virus
      maturation in both cases with equivalent numbers of nucleocapsids containing
      packaged viral DNA (C-capsids), indicating successful viral DNA replication,
      capsid assembly, and genome packaging. Most importantly, severe defects in virus
      envelopment were visualized in TKO cells but not in parental cells. Dynamin
      inhibitor (dynasore)-treated MEF showed a phenotype similar to TKO cells upon
      mouse cytomegalovirus infection, confirming the role of dynamin in late
      maturation processes. In summary, dynamin-mediated endocytic pathways are
      critical for the completion of cytoplasmic stages of cytomegalovirus
      maturation.IMPORTANCE Viruses are known to exploit specific cellular functions at
      different stages of their life cycle in order to replicate, avoid immune
      recognition by the host and to establish a successful infection. Cytomegalovirus
      (CMV)-infected cells are characterized by a prominent cytoplasmic inclusion
      (virus assembly compartment [vAC]) that is the site of virus maturation and
      envelopment. While endocytic membranes are known to be the functional components
      of vAC, knowledge of specific endocytic pathways implicated in CMV maturation and
      envelopment is lacking. We show here that dynamin, which is an integral part of
      host endocytic machinery, is largely dispensable for early stages of CMV
      infection but is required at a late stage of CMV maturation. Studies on dynamin
      function in CMV infection will help us understand the host-virus interaction
      pathways amenable to targeting by conventional small molecules, as well as by
      newer generation nucleotide-based therapeutics (e.g., small interfering RNA,
      CRISPR/CAS gRNA, etc.).

PMID- 30282705
TI  - Mapping the nonstructural protein interaction network of porcine reproductive and
      respiratory syndrome virus.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive
      stranded RNA virus belonging to the family Arteriviridae Synthesis of the viral
      RNA is directed by replication/transcription complexes (RTC) that are composed of
      mainly a network of PRRSV nonstructural proteins (nsps) and likely cellular
      proteins. Here we mapped the interaction network among PRRSV nsps by using yeast
      two hybrid screening in conjunction with co-immunoprecipitation (Co-IP) and co
      transfection assays. We identified a total of 24 novel interactions and found
      that the interactions were centered on ORF1b-encoded nsps that were mainly
      connected by the transmembrane proteins nsp2, nsp3 and nsp5. Interestingly, the
      interactions of the core enzymes nsp9 and nsp10 with transmembrane proteins did
      not occur in a straightforward manner, as they worked in the Co-IP assay but were
      poorly capable of finding each other within intact mammalian cells. Further proof
      that they can interact within cells required the engineering of N-terminal
      truncations of both nsp9 and nsp10. However, despite the poor co-localization
      relationship in co-transfected cells, both nsp9 and nsp10 came together with
      membrane proteins (e.g., nsp2) at the viral RTC in PRRSV-infected cells. Thus,
      our results indicate the existence of a complex interaction network among PRRSV
      nsps and raise the possibility that the recruitment of key replicase proteins to
      membrane-associated nsps may involve some regulatory mechanisms during
      infection.ImportanceSynthesis of PRRSV RNAs within host cells depends on the
      efficient and correct assembly of replication and transcription complexes (RTC)
      that takes places on modified intracellular membranes. As an important step
      toward dissecting this poorly understood event, we investigated the interaction
      network among PRRSV nsps. Our studies established a comprehensive interaction map
      for PRRSV nsps and revealed important players within the network. The results
      also highlight the likely existence of a regulated recruitment of PRRSV core
      enzymes nsp9 and nsp10 to viral membrane nsps during PRRSV RTC assembly.

PMID- 30282706
TI  - Nonpathogenic Heterologous Prions Can Interfere with Prion Infection in a Strain
      Dependent Manner.
AB  - Co-occurrence of different prion strains into the same host has been recognized
      as a natural phenomenon for several sporadic Creutzfeldt-Jakob disease (sCJD)
      patients and natural scrapie cases. The final outcome of prion coinfection is not
      easily predictable. In addition to the usual factors that influence prion
      conversion, the replication of one strain may entail positive or negative
      consequences to the other. The main aim of this study was to gain insights into
      the prion coinfection and interference concepts and their potential therapeutic
      implications. Here, different mouse models were challenged with several
      combinations of prion strains coupled on the basis of the lengths of their
      incubation periods and the existence/absence of a species barrier in the tested
      animal model. We found that nontransmissible strains can interfere the
      replication of fully transmissible strains when there is a species transmission
      barrier involved, as happened with the combination of a mouse (22L) and a human
      (sCJD) strain. However, this phenomenon seems to be strain dependent, since no
      interference was observed when the human strain coinoculated was vCJD. For the
      other combinations tested in this study, the results suggest that both strains
      replicate independently without effect on the replication of one over the other.
      It is common that the strain with more favorable conditions (e.g., a higher speed
      of disease development or the absence of a species barrier) ends being the only
      one detectable at the terminal stage of the disease. However, this does not
      exclude the replication of the least favored strain, leading to situations of the
      coexistence of prion strains.IMPORTANCE As a general conclusion, the outcome of
      prion coinfection is strongly dependent on the strain combination and the model
      utilized and is therefore difficult to predict. The coexistence of several prion
      strains may remain undetected if one of the strains has more favorable conditions
      to replicate in the host. The use of several models (such as a transgenic mouse
      expressing PrP from different species) to analyze field prion isolates is
      recommended to avoid this situation. The inference effect exerted by
      nonreplicative prion strains should be considered an interesting tool to advance
      in new therapeutic strategies for treating prion diseases; it may even be a
      proper therapeutic strategy.

PMID- 30282707
TI  - Herpes Simplex Virus 1 Latency and the Kinetics of Reactivation Are Regulated by
      a Complex Network of Interactions between the Herpesvirus Entry Mediator, Its
      Ligands (gD, BTLA, LIGHT, and CD160), and the Latency-Associated Transcript.
AB  - Recently, we reported that the herpesvirus entry mediator (HVEM; also called
      TNFRSF14 or CD270) is upregulated by the latency-associated transcript (LAT) of
      herpes simplex virus 1 (HSV-1) and that the absence of HVEM affects latency
      reactivation but not primary infection in ocularly infected mice. gD has been
      shown to bind to HVEM. LIGHT (TNFSF14), CD160, and BTLA (B- and T-lymphocyte
      attenuator) also interact with HVEM and can interfere with HSV gD binding. It was
      not known if LIGHT, CD160, or BTLA affected the level of latency reactivation in
      the trigeminal ganglia (TG) of latently infected mice. To address this issue, we
      ocularly infected LIGHT-/-, CD160-/-, and BTLA-/- mice with LAT(+) and LAT(-)
      viruses, using similarly infected wild-type (WT) and HVEM-/- mice as controls.
      The amount of latency, as determined by the levels of gB DNA in the TG of the
      LIGHT-/-, CD160-/-, and BTLA-/- mice infected with either LAT(+) or LAT(-)
      viruses, was lower than that in WT mice infected with LAT(+) virus and was
      similar in WT mice infected with LAT(-) virus. The levels of LAT RNA in HVEM-/-,
      LIGHT-/-, CD160-/-, and BTLA-/- mice infected with LAT(+) virus were similar and
      were lower than the levels of LAT RNA in WT mice. However, LIGHT-/-, CD160-/-,
      and BTLA-/- mice, independent of the presence of LAT, had levels of reactivation
      similar to those of WT mice infected with LAT(+) virus. Faster reactivation
      correlated with the upregulation of HVEM transcript. The LIGHT-/-, CD160-/-, and
      BTLA-/- mice had higher levels of HVEM expression, and this, along with the
      absence of BTLA, LIGHT, or CD160, may contribute to faster reactivation, while
      the absence of each molecule, independent of LAT, may have contributed to lower
      latency. This study suggests that, in the absence of competition with gD for
      binding to HVEM, LAT RNA is important for WT levels of latency but not for WT
      levels of reactivation.IMPORTANCE The effects of BTLA, LIGHT, and CD160 on
      latency reactivation are not known. We show here that in BTLA, LIGHT, or CD160
      null mice, latency is reduced; however, HVEM expression is upregulated compared
      to that of WT mice, and this upregulation is associated with higher reactivation
      that is independent of LAT but dependent on gD expression. Thus, one of the
      mechanisms by which BTLA, LIGHT, and CD160 null mice enhance reactivation appears
      to be the increased expression of HVEM in the presence of gD. Thus, our results
      suggest that blockade of HVEM-LIGHT-BTLA-CD160 contributes to reduced HSV-1
      latency and reactivation.

PMID- 30282708
TI  - Remodeling mTORC1 Responsiveness to Amino Acids by the Herpes Simplex Virus UL46
      and Us3 Gene Products Supports Replication during Nutrient Insufficiency.
AB  - By sensing fundamental parameters, including nutrient availability, activated
      mechanistic target of rapamycin complex 1 (mTORC1) suppresses catabolic outcomes
      and promotes anabolic processes needed for herpes simplex virus 1 (HSV-1)
      productive growth. While the virus-encoded Us3 Ser/Thr kinase is required to
      activate mTORC1, whether stress associated with amino acid insufficiency impacts
      mTORC1 activation in infected cells and virus reproduction was unknown. In
      contrast to uninfected cells, where amino acid withdrawal inhibits mTORC1
      activation, we demonstrate that mTORC1 activity is sustained in HSV-1-infected
      cells during amino acid insufficiency. We show that in the absence of Us3, the
      insensitivity of mTORC1 to amino acid withdrawal in infected cells was dependent
      on the host kinase Akt and establish a role for the HSV-1 UL46 gene product,
      which stimulates phosphatidylinositol (PI) 3-kinase signaling. Significantly,
      virus reproduction during amino acid insufficiency was stimulated by the viral
      UL46 gene product. By synergizing with Us3, UL46 reprograms mTORC1 such that it
      is insensitive to amino acid withdrawal and supports sustained mTORC1 activation
      and virus reproduction during amino acid insufficiency. This identifies an
      unexpected function for UL46 in supporting virus reproduction during
      physiological stress and identifies a new class of virus-encoded mTORC1
      regulators that selectively uncouple mTORC1 activation from amino acid
      sufficiency.IMPORTANCE Mechanistic target of rapamycin complex 1 (mTORC1) is a
      multisubunit cellular kinase that coordinates protein synthesis with changing
      amino acid levels. During amino acid insufficiency, mTORC1 is repressed in
      uninfected cells, dampening protein synthesis and potentially restricting virus
      reproduction. Here, we establish that HSV-1 alters the responsiveness of mTORC1
      to metabolic stress resulting from amino acid insufficiency. Unlike in uninfected
      cells, mTORC1 remains activated in HSV-1-infected cells deprived of amino acids.
      Synergistic action of the HSV-1 UL46 gene product, which stimulates PI 3-kinase,
      and the Us3 kinase supports virus reproduction during amino acid withdrawal.
      These results define how HSV-1, a medically important human pathogen associated
      with a range of diseases, uncouples mTORC1 activation from amino acid
      availability. Furthermore, they help explain how the virus reproduces during
      physiological stress. Reproduction triggered by physiological stress is
      characteristic of herpesvirus infections, where lifelong latency is punctuated by
      episodic reactivation events.

PMID- 30282709
TI  - Extracellular Hepatitis B Virus RNAs Are Heterogeneous in Length and Circulate as
      Capsid-Antibody Complexes in Addition to Virions in Chronic Hepatitis B Patients.
AB  - Extracellular HBV RNA has been detected in both HBV-replicating cell culture
      media and sera from chronic hepatitis B (CHB) patients, but its exact origin and
      composition remain controversial. Here, we demonstrated that extracellular HBV
      RNA species were of heterogeneous lengths, ranging from the length of pregenomic
      RNA to a few hundred nucleotides. In cell models, these RNAs were predominantly
      associated with naked capsids, although virions also harbored a minority of them.
      Moreover, HBV RNAs in hepatitis B patients' blood circulation were localized in
      unenveloped capsids in the form of capsid-antibody complexes (CACs) and in
      virions. Furthermore, we showed that extracellular HBV RNAs could serve as the
      template for viral DNA synthesis. In conclusion, extracellular HBV RNAs mainly
      consist of pgRNA or the pgRNA species degraded by the RNase H domain of the
      polymerase in the process of viral DNA synthesis and circulate as CACs and
      virions. Their presence in blood circulation of CHB patients may be exploited to
      develop novel biomarkers for HBV persistence.IMPORTANCE Although increasing
      evidence suggests the presence of extracellular HBV RNA species, their origin and
      molecular forms are still under debate. In addition to the infectious virions,
      HBV is known to secrete several species of incomplete viral particles, including
      hepatitis B surface antigen (HBsAg) particles, naked capsids, and empty virions,
      during its replication cycle. Here, we demonstrated that extracellular HBV RNAs
      were associated with naked capsids and virions in HepAD38 cells. Interestingly,
      we found that unenveloped capsids circulate in the blood of hepatitis B patients
      in the form of CACs and, together with virions, serve as vehicles carrying these
      RNA molecules. Moreover, extracellular HBV RNAs are heterogeneous in length and
      represent either pregenomic RNA (pgRNA) or products of incomplete reverse
      transcription during viral replication. These findings provide a conceptual basis
      for further application of extracellular RNA species as novel biomarkers for HBV
      persistence.

PMID- 30282710
TI  - Engineered small molecule control of influenza A virus replication.
AB  - Influenza A virus (IAV) remains a global health concern despite the availability
      of a seasonal vaccine. It is difficult to predict which strains will circulate
      during influenza season, and therefore extremely challenging to test novel
      vaccines in the human population. To overcome this obstacle, new vaccines must be
      tested in challenge studies. This approach poses significant safety problems, as
      current pharmacological interventions for IAV are poorly efficacious. New methods
      are needed to enhance the safety of these challenge studies. Here, we generate a
      virus expressing a small molecule-assisted shutoff (SMASh) tag as a safety switch
      for IAV replication. Addition of the SMASh tag to an essential IAV protein allows
      for small molecule-mediated inhibition of replication. Treatment with this drug
      controls SMASh-tagged virus replication in vitro and in vivo This model for
      restriction of viral replication has potential for broad applications in vaccine
      studies, virotherapy, and basic virus research.Importance Influenza A virus (IAV)
      causes significant morbidity and mortality worldwide annually, despite the
      availability of new formulations of the vaccine each season. There is a critical
      need to develop more efficacious vaccines. However, testing novel vaccines in the
      human population in controlled studies is difficult due to the limited
      availability and efficacy of intervention strategies should the vaccine fail.
      There are also significant safety concerns for work with highly pathogenic IAV
      strains in the laboratory. Therefore, novel strategies are needed to improve the
      safety of vaccine studies and highly pathogenic IAV research. Here we developed
      an IAV strain engineered to contain a small molecule-mediated safety switch. This
      tag, when attached to an essential viral protein, allows for regulation of IAV
      replication in vitro and in vivo This strategy provides a platform for regulation
      of virus replication without targeting viral proteins directly.

PMID- 30282711
TI  - Exosomes exploit the virus entry machinery and pathway to transmit IFN-alpha
      induced antiviral activity.
AB  - Interferon-alpha (IFN-alpha) induces the transfer of resistance to hepatitis B
      virus (HBV) from liver nonparenchymal cells (LNPCs) to hepatocytes via exosomes.
      However, little is known about the entry machinery and pathway involved in the
      transmission of IFN-alpha-induced antiviral activity. Here, we found that
      macrophage exosomes uniquely depend on T cell immunoglobulin and mucin receptor 1
      (TIM-1), a hepatitis A virus (HAV) receptor, to enter hepatocytes for delivering
      IFN-alpha-induced anti-HBV activity. Moreover, two primary endocytic routes for
      virus infection, clathrin-mediated endocytosis (CME) and macropinocytosis,
      collaborate to permit exosome entry and anti-HBV activity transfer. Subsequently,
      lysobisphosphatidic acid (LBPA), an anionic lipid closely related to endosome
      penetration of virus, facilitates membrane fusion of exosomes in late
      endosomes/multivesicular bodies (LEs/MVBs) and the accompanying exosomal cargo
      uncoating. Together, this study provides comprehensive insights into the
      transmission route of macrophage exosomes to efficiently deliver IFN-alpha
      induced antiviral substances and highlights the similarities between the entry
      mechanisms of exosomes and virus.Importance Our previous study showed that LNPC
      derived exosomes could transmit IFN-alpha-induced antiviral activity to HBV
      replicating hepatocytes, but the concrete transmission mechanisms which include
      exosome entry and exosomal cargo release remain unclear. In this study, we found
      that virus entry machinery and pathway were also applied to exosome-mediated cell
      to-cell antiviral activity transfer. Macrophage-derived exosomes distinctively
      exploit hepatitis A virus receptor for access to hepatocytes. Later, CME and
      macropinocytosis are utilized by exosomes which is followed by exosome-endosome
      fusion for efficient transfer of IFN-alpha-induced anti-HBV activity. We believe
      that understanding the cellular entry pathway of exosomes will be beneficial to
      designing exosomes as efficient vehicles for antiviral therapy.

PMID- 30282712
TI  - Phosphatidylinositol 3-Kinase/Akt and MEK/ERK Signaling Pathways Facilitate
      Sapovirus Trafficking and Late Endosomal Acidification for Viral Uncoating in LLC
      PK Cells.
AB  - Sapovirus, an important cause of acute gastroenteritis in humans and animals,
      travels from the early to the late endosomes and requires late endosomal
      acidification for viral uncoating. However, the signaling pathways responsible
      for these viral entry processes remain unknown. Here we demonstrate the receptor
      mediated early activation of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen
      activated protein extracellular signal-regulated kinase/extracellular signal
      regulated kinase (MEK/ERK) signaling pathways involved in sapovirus entry
      processes. Both signaling pathways were activated during the early stage of
      porcine sapovirus (PSaV) infection. However, depletion of the cell surface
      carbohydrate receptors by pretreatment with sodium periodate or neuraminidase
      reduced the PSaV-induced early activation of these signaling pathways, indicating
      that PSaV binding to the cell surface carbohydrate receptors triggered these
      cascades. Addition of bile acid, known to be essential for PSaV escape from late
      endosomes, was also found to exert a stiffening effect to stimulate both
      pathways. Inhibition of these signaling pathways by use of inhibitors specific
      for PI3K or MEK or small interfering RNAs (siRNAs) against PI3K or MEK resulted
      in entrapment of PSaV particles in early endosomes and prevented their
      trafficking to late endosomes. Moreover, phosphorylated PI3K and ERK
      coimmunoprecipitated subunit E of the V-ATPase proton pump that is important for
      endosomal acidification. Based on our data, we conclude that receptor binding of
      PSaV activates both PI3K/Akt and MEK/ERK signaling pathways, which in turn
      promote PSaV trafficking from early to late endosomes and acidification of late
      endosomes for PSaV uncoating. These signaling cascades may provide a target for
      potent therapeutics against infections by PSaV and other caliciviruses.IMPORTANCE
      Sapoviruses cause acute gastroenteritis in both humans and animals. However, the
      host signaling pathway(s) that facilitates host cell entry by sapoviruses remains
      largely unknown. Here we demonstrate that porcine sapovirus (PSaV) activates both
      PI3K/Akt and MEK/ERK cascades at an early stage of infection. Removal of cell
      surface receptors decreased PSaV-induced early activation of both cascades.
      Moreover, blocking of PI3K/Akt and MEK/ERK cascades entrapped PSaV particles in
      early endosomes and prevented their trafficking to the late endosomes. PSaV
      induced early activation of PI3K and ERK molecules further mediated V-ATPase
      dependent late endosomal acidification for PSaV uncoating. This work unravels a
      new mechanism by which receptor-mediated early activation of both cascades may
      facilitate PSaV trafficking from early to late endosomes and late endosomal
      acidification for PSaV uncoating, which in turn can be a new target for treatment
      of sapovirus infection.

PMID- 30282713
TI  - Salinomycin Inhibits Influenza Virus Infection by Disrupting Endosomal
      Acidification and Viral Matrix Protein 2 Function.
AB  - Screening of chemical libraries with 2,000 synthetic compounds identified
      salinomycin as a hit against influenza A and B viruses, with 50% effective
      concentrations ranging from 0.4 to 4.3 MUM in cells. This compound is a
      carboxylic polyether ionophore that exchanges monovalent ions for protons across
      lipid bilayer membranes. Monitoring the time course of viral infection showed
      that salinomycin blocked nuclear migration of viral nuclear protein (NP), the
      most abundant component of the viral ribonucleoprotein (vRNP) complex. It caused
      cytoplasmic accumulation of NP, particularly within perinuclear endosomes, during
      virus entry. This was primarily associated with failure to acidify the endosomal
      lysosomal compartments. Similar to the case with amantadine (AMT), proton channel
      activity of viral matrix protein 2 (M2) was blocked by salinomycin. Using
      purified retroviral Gag-based virus-like particles (VLPs) with M2, it was proved
      that salinomycin directly affects the kinetics of a proton influx into the
      particles but in a manner different from that of AMT. Notably, oral
      administration of salinomycin together with the neuraminidase inhibitor
      oseltamivir phosphate (OSV-P) led to enhanced antiviral effect over that with
      either compound used alone in influenza A virus-infected mouse models. These
      results provide a new paradigm for developing antivirals and their combination
      therapy that control both host and viral factors.IMPORTANCE Influenza virus is a
      main cause of viral respiratory infection in humans as well as animals,
      occasionally with high mortality. Circulation of influenza viruses resistant to
      the matrix protein 2 (M2) inhibitor, amantadine, is highly prevalent. Moreover,
      the frequency of detection of viruses resistant to the neuraminidase inhibitors,
      including oseltamivir phosphate (OSV-P) or zanamivir, is also increasing. These
      issues highlight the need for discovery of new antiviral agents with different
      mechanisms. Salinomycin as the monovalent cation-proton antiporter exhibited
      consistent inhibitory effects against influenza A and B viruses. It plays
      multifunctional roles by blocking endosomal acidification and by inactivating the
      proton transport function of M2, the key steps for influenza virus uncoating.
      Notably, salinomycin resulted in marked therapeutic effects in influenza virus
      infected mice when combined with OSV-P, suggesting that its chemical derivatives
      could be developed as an adjuvant antiviral therapy to treat influenza infections
      resistant or less sensitive to existing drugs.

PMID- 30282714
TI  - Amino acid residue 217 in the hemagglutinin glycoprotein is a key mediator of
      avian influenza H7N9 virus antigenicity.
AB  - Avian influenza viruses continue to evolve and acquire mutations that facilitate
      antigenic drift and virulence change. In 2017, low pathogenicity H7N9 avian
      influenza viruses evolved to a high pathogenicity phenotype in China. The
      comparative antigenic analysis between the low and high pathogenicity virus
      strains showed marked variability. In order to identify residues that may be
      linked to the antigenic change amongst the H7N9 viruses, we serially passaged the
      viruses in the presence of homologous ferret antisera. Progeny viruses able to
      overcome the neutralising capacity of the antisera were sequenced. The analysis
      showed that the emergent immune escaped viruses contained mutations A125T, A151T
      and L217Q in the hemagglutinin (HA) glycoprotein as early as passage 5 and these
      mutations persisted until passage 10. The results revealed that a single mutation
      L217Q in the HA of H7N9 virus led to 23- and 8-fold reductions in
      hemagglutination inhibition (HI) titre with ferret and chicken antisera,
      respectively. Further analysis showed that this change also contributed to
      antigenic differences between the low and high pathogenicity H7N9 viruses,
      therein, playing a major role in their antigenic diversification. Therefore,
      evolutionary changes at amino acid position 217 in the H7N9 viruses can serve as
      a genetic marker for virus antigenic diversity during vaccine seed matching and
      selection. The in vitro immune escape mutant selection method used in this study
      could also aid in the prediction of emerging antigenic variants in the naturally
      infected or immunised animals.IMPORTANCE Avian influenza H7N9 viruses circulating
      in poultry and wild birds continue to evolve and acquire important phenotypic
      changes. Mutations to the virus hemagglutinin (HA) glycoprotein can modulate
      virus antigenicity and facilitate virus escape from natural or vaccine-induced
      immunity. The focus of this study was to identify evolutionary markers in the HA
      of H7N9 that drive escape from antibody-based immunity. To achieve this, we
      propagated low pathogenicity H7N9 virus in the presence of polyclonal antisera
      derived from ferrets infected with the same strain of virus (homologous
      antisera). This selection process was repeated 10 times. The HA gene sequence of
      viruses recovered after the 5th passage showed that the viruses readily acquired
      mutation at three different amino acid positions (A125T, A151T and L217Q).
      Further functional analysis of these mutations confirmed that mutation at residue
      HA 217 was responsible for mediating changes to the immunological properties of
      the H7N9 virus.

PMID- 30282715
TI  - Using Antibodies and Mutants To Localize the Presumptive gH/gL Binding Site on
      Herpes Simplex Virus gD.
AB  - HSV virus-cell and cell-cell fusion requires multiple interactions between four
      essential virion envelope glycoproteins, gD, gB, gH, and gL, and between gD and a
      cellular receptor, nectin-1 or herpesvirus entry mediator (HVEM). Current models
      suggest that binding of gD to receptors induces a conformational change that
      leads to activation of gH/gL and consequent triggering of the prefusion form of
      gB to promote membrane fusion. Since protein-protein interactions guide each step
      of fusion, identifying the sites of interaction may lead to the identification of
      potential therapeutic targets that block this process. We have previously
      identified two "faces" on gD: one for receptor binding and the other for its
      presumed interaction with gH/gL. We previously separated the gD monoclonal
      antibodies (MAbs) into five competition communities. MAbs from two communities
      (MC2 and MC5) neutralize virus infection and block cell-cell fusion but do not
      block receptor binding, suggesting that they block binding of gD to gH/gL. Using
      a combination of classical epitope mapping of gD mutants with fusion and entry
      assays, we identified two residues (R67 and P54) on the presumed gH/gL
      interaction face of gD that allowed for fusion and viral entry but were no longer
      sensitive to inhibition by MC2 or MC5, yet both were blocked by other MAbs. As
      neutralizing antibodies interfere with essential steps in the fusion pathway, our
      studies strongly suggest that these key residues block the interaction of gD with
      gH/gL.IMPORTANCE Virus entry and cell-cell fusion mediated by HSV require gD,
      gH/gL, gB, and a gD receptor. Neutralizing antibodies directed against any of
      these proteins bind to residues within key functional sites and interfere with an
      essential step in the fusion pathway. Thus, the epitopes of these MAbs identify
      critical, functional sites on their target proteins. Unlike many anti-gD MAbs,
      which block binding of gD to a cellular receptor, two, MC2 and MC5, block a
      separate, downstream step in the fusion pathway which is presumed to be the
      activation of the modulator of fusion, gH/gL. By combining epitope mapping of a
      panel of gD mutants with fusion and virus entry assays, we have identified
      residues that are critical in the binding and function of these two MAbs. This
      new information helps to define the site of the presumptive interaction of gD
      with gH/gL, of which we have limited knowledge.

PMID- 30282716
TI  - Targeting of the Nasal Mucosa by Japanese Encephalitis Virus for Non-Vector-Borne
      Transmission.
AB  - The mosquito-borne Japanese encephalitis virus (JEV) causes severe central
      nervous system diseases and cycles between Culex mosquitoes and different
      vertebrates. For JEV and some other flaviviruses, oronasal transmission is
      described, but the mode of infection is unknown. Using nasal mucosal tissue
      explants and primary porcine nasal epithelial cells (NEC) at the air-liquid
      interface (ALI) and macrophages as ex vivo and in vitro models, we determined
      that the nasal epithelium could represent the route of entry and exit for JEV in
      pigs. Porcine NEC at the ALI exposed to with JEV resulted in apical and
      basolateral virus shedding and release of monocyte recruiting chemokines,
      indicating infection and replication in macrophages. Moreover, macrophages
      stimulated by alarmins, including interleukin-25, interleukin-33, and thymic
      stromal lymphopoietin, were more permissive to the JEV infection. Altogether, our
      data are important to understand the mechanism of non-vector-borne direct
      transmission of Japanese encephalitis virus in pigs.IMPORTANCE JEV, a main cause
      of severe viral encephalitis in humans, has a complex ecology composed of a
      mosquito-waterbird cycle and a cycle involving pigs, which amplifies virus
      transmission to mosquitoes, leading to increased human cases. JEV can be
      transmitted between pigs by contact in the absence of arthropod vectors.
      Moreover, virus or viral RNA is found in oronasal secretions and the nasal
      epithelium. Using nasal mucosa tissue explants and three-dimensional porcine
      nasal epithelial cells cultures and macrophages as ex vivo and in vitro models,
      we determined that the nasal epithelium could be a route of entry as well as exit
      for the virus. Infection of nasal epithelial cells resulted in apical and
      basolateral virus shedding and release of monocyte recruiting chemokines and
      therefore infection and replication in macrophages, which is favored by
      epithelial-cell-derived cytokines. The results are relevant to understand the
      mechanism of non-vector-borne direct transmission of JEV.

PMID- 30282717
TI  - The Nonstructural Protein 11-kDa of Human Parvovirus B19 Facilitates Viral DNA
      Replication by Interacting with Grb2 through Its Proline-rich Motifs.
AB  - Lytic infection of human parvovirus B19 (B19V) takes place exclusively in human
      erythroid progenitor cells of bone marrow and fetal liver, which disrupts
      erythropoiesis. During infection, B19V expresses three nonstructural proteins
      (NS1, 11-kDa, and 7.5-kDa) and two structural proteins (VP1 and VP2). While NS1
      is essential for B19V DNA replication, the 11-kDa enhances viral DNA replication
      significantly. In this study, we confirmed the enhancement role of the 11-kDa in
      viral DNA replication and elucidated the underlying mechanism. We found that 11
      kDa specially interacts with cellular growth factor receptor-bound protein 2
      (Grb2) during virus infection and in vitro We determined a high affinity
      interaction between 11-kDa and Grb2 that has an equilibrium dissociation constant
      (KD) value of 18.13 nM. In vitro, one proline-rich motif was sufficient for 11
      kDa to sustain a strong interaction with Grb2. In consistence, in vivo during
      infection, one proline-rich motif was enough for 11-kDa to significantly reduce
      phosphorylation of extracellular signal-regulated kinase (ERK). Mutations of all
      three proline-rich motifs of the 11-kDa abolished its capability to reduce ERK
      activity, and accordingly, decreased viral DNA replication. Transduction of a
      lentiviral vector encoding an shRNA targeting Grb2 decreased the expression of
      Grb2 as well as the level of ERK phosphorylation, which results in an increase of
      B19V replication. These results, in concert, indicate that the B19V 11-kDa
      interacts with cellular Grb2 to downregulate ERK activity, which upregulates
      viral DNA replication.SIGNIFICANCE Human parvovirus B19 (B19V) infection causes
      hematological disorders and is the leading cause of non-immunological fetal
      hydrops during pregnancy. During infection, B19V expresses two structural
      proteins VP1/VP2 and three nonstructural proteins, NS1, 11-kDa, and 7.5-kDa.
      While NS1 is essential, 11-kDa plays an enhancing role in viral DNA replication.
      Here we elucidated a mechanism underlying the 11-kDa regulated B19V DNA
      replication. 11-kDa is tightly associated with cellular growth factor receptor
      bound protein 2 (Grb2) during infection. In vitro, 11-kDa interacts with Grb2 at
      a high affinity through three proline-rich motifs, of which at least one is
      indispensable for the regulation of viral DNA replication. 11-kDa and Grb2
      interaction disrupts the extracellular signal-regulated kinase (ERK) signaling,
      which mediates upregulation of B19V replication. Thus, our study reveals a novel
      mechanism of how a parvoviral small nonstructural protein regulates viral DNA
      replication through interacting with a host protein that is predominately
      expressed in the cytoplasm.

PMID- 30282718
TI  - The Abundant Tegument Protein pUL25 of Human Cytomegalovirus Prevents Proteasomal
      Degradation of pUL26 and Supports Its Suppression of ISGylation.
AB  - The tegument of human cytomegalovirus (HCMV) virions contains proteins that
      interfere with both the intrinsic and the innate immunity. One protein with a
      thus far unknown function is pUL25. The deletion of pUL25 in a viral mutant
      (Towne-DeltaUL25) had no impact on the release of virions and subviral dense
      bodies or on virion morphogenesis. Proteomic analyses showed few alterations in
      the overall protein composition of extracellular particles. A surprising result,
      however, was the almost complete absence of pUL26 in virions and dense bodies of
      Towne-DeltaUL25 and a reduction of the large isoform pUL26-p27 in mutant virus
      infected cells. pUL26 had been shown to inhibit protein conjugation with the
      interferon-stimulated gene 15 protein (ISG15), thereby supporting HCMV
      replication. To test for a functional relationship between pUL25 and pUL26, we
      addressed the steady-state levels of pUL26 and found them to be reduced in Towne
      DeltaUL25-infected cells. Coimmunoprecipitation experiments proved an interaction
      between pUL25 and pUL26. Surprisingly, the overall protein ISGylation was
      enhanced in Towne-DeltaUL25-infected cells, thus mimicking the phenotype of a
      pUL26-deleted HCMV mutant. The functional relevance of this was confirmed by
      showing that the replication of Towne-DeltaUL25 was more sensitive to beta
      interferon. The increase of protein ISGylation was also seen in cells infected
      with a mutant lacking the tegument protein pp65. Upon retesting, we found that
      pUL26 degradation was also increased when pp65 was unavailable. Our experiments
      show that both pUL25 and pp65 regulate pUL26 degradation and the pUL26-dependent
      reduction of ISGylation and add pUL25 as another HCMV tegument protein that
      interferes with the intrinsic immunity of the host cell.IMPORTANCE Human
      cytomegalovirus (HCMV) expresses a number of tegument proteins that interfere
      with the intrinsic and the innate defense mechanisms of the cell. Initial
      induction of the interferon-stimulated gene 15 protein (ISG15) and conjugation of
      proteins with ISG15 (ISGylation) by HCMV infection are subsequently attenuated by
      the expression of the viral IE1, pUL50, and pUL26 proteins. This study adds pUL25
      as another factor that contributes to suppression of ISGylation. The tegument
      protein interacts with pUL26 and prevents its degradation by the proteasome. By
      doing this, it supports its restrictive influence on ISGylation. In addition, a
      lack of pUL25 enhances the levels of free ISG15, indicating that the tegument
      protein may interfere with the interferon response on levels other than
      interacting with pUL26. Knowledge obtained in this study widens our understanding
      of HCMV immune evasion and may also provide a new avenue for the use of pUL25
      negative strains for vaccine production.

PMID- 30282720
TI  - CORRIGENDUM.

PMID- 30282721
TI  - Interactive effect between ATPase-related genes and early-life tobacco smoke
      exposure on bronchial hyper-responsiveness detected in asthma-ascertained
      families.
AB  - BACKGROUND: A positional cloning study of bronchial hyper-responsiveness (BHR) at
      the 17p11 locus in the French Epidemiological study on the Genetics and
      Environment of Asthma (EGEA) families showed significant interaction between
      early-life environmental tobacco smoke (ETS) exposure and genetic variants
      located in DNAH9. This gene encodes the heavy chain subunit of axonemal dynein,
      which is involved with ATP in the motile cilia function.Our goal was to identify
      genetic variants at other genes interacting with ETS in BHR by investigating all
      genes belonging to the 'ATP-binding' and 'ATPase activity' pathways which include
      DNAH9, are targets of cigarette smoke and play a crucial role in the airway
      inflammation. METHODS: Family-based interaction tests between ETS-exposed and
      unexposed BHR siblings were conducted in 388 EGEA families. Twenty single
      nucleotide polymorphisms (SNP) showing interaction signals (p<=5.10-3) were
      tested in the 253 Saguenay-Lac-Saint-Jean (SLSJ) families. RESULTS: One of these
      SNPs was significantly replicated for interaction with ETS in SLSJ families
      (p=0.003). Another SNP reached the significance threshold after correction for
      multiple testing in the combined analysis of the two samples (p=10-5). Results
      were confirmed using both a robust log-linear test and a gene-based interaction
      test. CONCLUSION: The SNPs showing interaction with ETS belong to the ATP8A1 and
      ABCA1 genes, which play a role in the maintenance of asymmetry and homeostasis of
      lung membrane lipids.

PMID- 30282719
TI  - Neutrophils instruct homeostatic and pathological states in naive tissues.
AB  - Immune protection relies on the capacity of neutrophils to infiltrate challenged
      tissues. Naive tissues, in contrast, are believed to remain free of these cells
      and protected from their toxic cargo. Here, we show that neutrophils are endowed
      with the capacity to infiltrate multiple tissues in the steady-state, a process
      that follows tissue-specific dynamics. By focusing in two particular tissues, the
      intestine and the lungs, we find that neutrophils infiltrating the intestine are
      engulfed by resident macrophages, resulting in repression of Il23 transcription,
      reduced G-CSF in plasma, and reinforced activity of distant bone marrow niches.
      In contrast, diurnal accumulation of neutrophils within the pulmonary vasculature
      influenced circadian transcription in the lungs. Neutrophil-influenced
      transcripts in this organ were associated with carcinogenesis and migration.
      Consistently, we found that neutrophils dictated the diurnal patterns of lung
      invasion by melanoma cells. Homeostatic infiltration of tissues unveils a facet
      of neutrophil biology that supports organ function, but can also instigate
      pathological states.

PMID- 30282722
TI  - Patient outcomes from time of listing for lung transplantation in the UK: are
      there disease-specific differences?
AB  - BACKGROUND: The demand for lung transplantation vastly exceeds the availability
      of donor organs. This translates into long waiting times and high waiting list
      mortality. We set out to examine factors influencing patient outcomes from the
      time of listing for lung transplantation in the UK, examining for differences by
      patient characteristics, lung disease category and transplant centre. METHODS:
      Data were obtained from the UK Transplant Registry held by NHS Blood and
      Transplant for adult lung-only registrations between 1January 2004 and 31 March
      2014. Pretransplant and post-transplant outcomes were evaluated against lung
      disease category, blood group and height. RESULTS: Of the 2213 patient
      registrations, COPD comprised 28.4%, pulmonary fibrosis (PF) 26.2%, cystic
      fibrosis (CF) 25.4% and other lung pathologies 20.1%. The chance of
      transplantation after listing differed by the combined effect of disease category
      and centre (p<0.001). At 3 years postregistration, 78% of patients with COPD were
      transplanted followed by 61% of patients with CF, 59% of other lung pathology
      patients and 48% of patients with PF, who also had the highest waiting list
      mortality (37%). The chance of transplantation also differed by height with
      taller patients having a greater chance of transplant (HR: 1.03, 95% CI: 1.02 to
      1.04, p<0.001). Patients with blood group O had the highest waiting mortality at
      3 years postregistration compared with all other blood groups (27% vs 20%,
      p<0.001). CONCLUSIONS: The way donor lungs were allocated in the UK resulted in
      discrepancies between the risk profile and probability of lung transplantation. A
      new donor lung allocation scheme was introduced in 2017 to try to address these
      shortcomings.

PMID- 30282723
TI  - Phosphocreatine Levels in the Left Thalamus Decline during Wakefulness and
      Increase after a Nap.
AB  - Scientists have hypothesized that the availability of phosphocreatine (PCr) and
      its ratio to inorganic phosphate (Pi) in cerebral tissue form a substrate of
      wakefulness. It follows then, according to this hypothesis, that the exhaustion
      of PCr and the decline in the ratio of PCr to Pi form a substrate of fatigue. We
      used 31P-magnetic resonance spectroscopy (31P-MRS) to investigate quantitative
      levels of PCr, the gamma-signal of ATP, and Pi in 30 healthy humans (18 female)
      in the morning, in the afternoon, and while napping (n = 15) versus awake
      controls (n = 10). Levels of PCr (2.40 mM at 9 A.M.) decreased by 7.0 +/- 0.8% (p
      = 7.1 * 10-6, t = -5.5) in the left thalamus between 9 A.M. and 5 P.M. Inversely,
      Pi (0.74 mM at 9 A.M.) increased by 17.1 +/- 5% (p = 0.005, t = 3.1) and pH
      levels dropped by 0.14 +/- 0.07 (p = 0.002; t = 3.6). Following a 20 min nap
      after 5 P.M., local PCr, Pi, and pH were restored to morning levels. We did not
      find respective significant changes in the contralateral thalamus or in other
      investigated brain regions. Left hemispheric PCr was signficantly lower than
      right hemispheric PCr only at 5 P.M. in the thalamus and at all conditions in the
      temporal region. Thus, cerebral daytime-related and sleep-related molecular
      changes are accessible in vivo Prominent changes were identified in the thalamus.
      This region is heavily relied on for a series of energy-consuming tasks, such as
      the relay of sensory information to the cortex. Furthermore, our data confirm
      that lateralization of brain function is regionally dynamic and includes
      PCr.SIGNIFICANCE STATEMENT The metabolites phosphocreatine (PCr) and inorganic
      phosphate (Pi) are assumed to inversely reflect the cellular energy load. This
      study detected a diurnal decrease of intracellular PCr and a nap-associated
      reincrease in the left thalamus. Pi behaved inversely. This outcome corroborates
      the role of the thalamus as a region of high energy consumption in agreement with
      its function as a gateway that relays and modulates information flow. Conversely
      to the dynamic lateralization of thalamic PCr, a constantly significant
      lateralization was observed in other regions. Increasing fatigue over the course
      of the day may also be a matter of cerebral energy supply. Comparatively fast
      restoration of that supply may be part of the biological basis for the
      recreational value of "power napping."

PMID- 30282724
TI  - Opposite Dynamics of GABA and Glutamate Levels in the Occipital Cortex during
      Visual Processing.
AB  - Magnetic resonance spectroscopy (MRS) measures the two most common inhibitory and
      excitatory neurotransmitters, GABA and glutamate, in the human brain. However,
      the role of MRS-derived GABA and glutamate signals in relation to system-level
      neural signaling and behavior is not fully understood. In this study, we
      investigated levels of GABA and glutamate in the visual cortex of healthy human
      participants (both genders) in three functional states with increasing visual
      input. Compared with a baseline state of eyes closed, GABA levels decreased after
      opening the eyes in darkness and Glx levels remained stable during eyes open but
      increased with visual stimulation. In relevant states, GABA and Glx correlated
      with amplitude of fMRI signal fluctuations. Furthermore, visual discriminatory
      performance correlated with the level of GABA, but not Glx. Our study suggests
      that differences in brain states can be detected through the contrasting dynamics
      of GABA and Glx, which has implications in interpreting MRS
      measurements.SIGNIFICANCE STATEMENT GABA and glutamate are the two most abundant
      neurotransmitters in human brain. Their interaction, known as inhibitory
      excitatory balance, plays a crucial role in establishing spontaneous and stimulus
      driven brain activity. Yet, the relationship between magnetic resonance
      spectroscopy (MRS)-derived levels of both metabolites and fMRI is still a matter
      of dispute. In this work, we study GABA and glutamate in three states of visual
      processing and in relation to fMRI and visual discriminatory performance in
      healthy people. We found that states of visual processing can be detected through
      the contrasting dynamics of GABA and glutamate and their correlation with fMRI
      signals. We also demonstrated that GABA, but not glutamate, in the visual system
      predicts visual performance. Our results provide insights into MRS-derived GABA
      and glutamate measurements.

PMID- 30282725
TI  - Nonlinear Lateral Interactions in V1 Population Responses Explained by a Contrast
      Gain Control Model.
AB  - How do cortical responses to local image elements combine to form a spatial
      pattern of population activity in primate V1? Here, we used voltage-sensitive dye
      imaging, which measures summed membrane potential activity, to examine the rules
      that govern lateral interactions between the representations of two small local
      oriented elements in macaque (Macaca mulatta) V1. We find strong subadditive and
      mostly orientation-independent interactions for nearby elements [2-4 mm
      interelement cortical distance (IED)] that gradually become linear at larger
      separations (>6 mm IED). These results are consistent with a population gain
      control model describing nonlinear V1 population responses to single oriented
      elements. However, because of the membrane potential-to-spiking accelerating
      nonlinearity, the model predicts supra-additive lateral interactions of spiking
      responses for intermediate separations at a range of locations between the two
      elements, consistent with some prior facilitatory effects observed in
      electrophysiology and psychophysics. Overall, our results suggest that population
      level lateral interactions in V1 are primarily explained by a simple orientation
      independent contrast gain control mechanism.SIGNIFICANCE STATEMENT Interactions
      between representations of simple visual elements such as oriented edges in
      primary visual cortex (V1) are thought to contribute to our ability to easily
      integrate contours and segment surfaces, but the mechanisms that govern these
      interactions are primarily unknown. Our study provides novel evidence that
      lateral interactions at the population level are governed by a simple contrast
      gain-control mechanism, and we show how this divisive gain-control mechanism can
      give rise to apparently facilitatory spiking responses.

PMID- 30282726
TI  - Nucleus Reuniens Is Required for Encoding and Retrieving Precise, Hippocampal
      Dependent Contextual Fear Memories in Rats.
AB  - The nucleus reuniens (RE) is a ventral midline thalamic nucleus that
      interconnects the medial prefrontal cortex (mPFC) and hippocampus (HPC).
      Considerable data indicate that HPC-mPFC circuits are involved in contextual and
      spatial memory; however, it is not clear whether the RE mediates the acquisition
      or retrieval of these memories. To examine this question, we inactivated the RE
      with muscimol before either the acquisition or retrieval of pavlovian fear
      conditioning in rats; freezing served as the index of fear. We found that RE
      inactivation before conditioning impaired the acquisition of contextual freezing,
      whereas inactivation of the RE before retrieval testing increased the
      generalization of freezing to a novel context; inactivation of the RE did not
      affect either the acquisition or expression of auditory fear conditioning.
      Interestingly, contextual conditioning impairments were absent when retrieval
      testing was also conducted after RE inactivation. Contextual memories acquired
      under RE inactivation were hippocampal independent, insofar as contextual
      freezing in rats conditioned under RE inactivation was insensitive to
      intrahippocampal infusions of the NMDA receptor antagonist
      aminophosphonovalerate. Together, these data reveal that the RE supports
      hippocampal-dependent encoding of precise contextual memories that allow
      discrimination of dangerous contexts from safe contexts. When the RE is inactive,
      however, alternate neural systems acquire an impoverished contextual memory that
      is expressed only when the RE is off-line.SIGNIFICANCE STATEMENT The midline
      thalamic nucleus reuniens (RE) coordinates communication between the hippocampus
      and medial prefrontal cortex, brain areas that are critical for contextual and
      spatial memory. Here we show that temporary pharmacological inactivation of RE
      impairs the acquisition and precision of contextual fear memories after pavlovian
      fear conditioning in rats. However, inactivating the RE before retrieval testing
      restored contextual memory in rats conditioned after RE inactivation. Critically,
      we show that imprecise contextual memories acquired under RE inactivation are
      learned independently of the hippocampus. These data reveal that the RE is
      required for hippocampal-dependent encoding of precise contextual memories to
      support the discrimination of safe and dangerous contexts.

PMID- 30282727
TI  - A Pool of Postnatally Generated Interneurons Persists in an Immature Stage in the
      Olfactory Bulb.
AB  - Calretinin (CR)-expressing periglomerular (PG) cells are the most abundant
      interneurons in the glomerular layer of the olfactory bulb. They are
      predominately generated postnatally from the septal and dorsal subventricular
      zones that continue producing them well into adulthood. Yet, little is known
      about their properties and functions. Using transgenic approaches and patch-clamp
      recording in mice of both sexes we show that CR(+) PG cells of both septal and
      dorsal origin have homogeneous morphological and electrophysiological properties.
      However, unlike other PG cells, these axonless neurons express a surprisingly
      small repertoire of voltage-activated channels and do not fire or fire at most a
      single and often small action potential. Moreover, they are not innervated by
      olfactory sensory neurons and receive little synaptic inputs from mitral or
      tufted cells at excitatory synapses where NMDA receptors predominate. These
      membrane and synaptic properties, that resemble those of newborn immature neurons
      not yet integrated in the network, persist over time and limit the recruitment of
      CR(+) PG cells by afferent inputs that strongly drive local network activity.
      Together, our results show that postnatally generated CR(+) PG cells continuously
      supply a large pool of neurons with unconventional properties. These data also
      question the contribution of CR(+) PG cells in olfactory bulb
      computation.SIGNIFICANCE STATEMENT Calretinin-expressing PG cells are by far the
      most abundant interneurons in the glomerular layer of the olfactory bulb. They
      are continuously produced during postnatal life, including adulthood, from neural
      stem cells located in the subventricular zones. Surprisingly, unlike other
      postnatally generated newborn neurons that quickly integrate into preexisting
      olfactory bulb networks, calretinin-expressing PG cells retain immature
      properties that limit their recruitment in local network activity for weeks, if
      not months, as if they would never fully mature. The function of this so far
      unsuspected pool of latent neurons is still unknown.

PMID- 30282728
TI  - Aggrecan Directs Extracellular Matrix-Mediated Neuronal Plasticity.
AB  - In the adult brain, the extracellular matrix (ECM) influences recovery after
      injury, susceptibility to mental disorders, and is in general a strong regulator
      of neuronal plasticity. The proteoglycan aggrecan is a core component of the
      condensed ECM structures termed perineuronal nets (PNNs), and the specific role
      of PNNs on neural plasticity remains elusive. Here, we genetically targeted the
      Acan gene encoding for aggrecan using a novel animal model. This allowed for
      conditional and targeted loss of aggrecan in vivo, which ablated the PNN
      structure and caused a shift in the population of parvalbumin-expressing
      inhibitory interneurons toward a high plasticity state. Selective deletion of the
      Acan gene in the visual cortex of male adult mice reinstated juvenile ocular
      dominance plasticity, which was mechanistically identical to critical period
      plasticity. Brain-wide targeting improved object recognition memory.SIGNIFICANCE
      STATEMENT The study provides the first direct evidence of aggrecan as the main
      functional constituent and orchestrator of perineuronal nets (PNNs), and that
      loss of PNNs by aggrecan removal induces a permanent state of critical period
      like plasticity. Loss of aggrecan ablates the PNN structure, resulting in invoked
      juvenile plasticity in the visual cortex and enhanced object recognition memory.

PMID- 30282729
TI  - Sleep and Wakefulness Are Controlled by Ventral Medial Midbrain/Pons GABAergic
      Neurons in Mice.
AB  - Sleep-wake behavior is controlled by a wide range of neuronal populations in the
      mammalian brain. Although the ventral midbrain/pons (VMP) area is suggested to
      participate in sleep-wake regulation, the neuronal mechanisms have remained
      unclear. Here, we found that nonspecific cell ablation or selective ablation of
      GABAergic neurons by expressing diphtheria toxin fragment A in the VMP in male
      mice induced a large increase in wakefulness that lasted at least 4 weeks. In
      contrast, selective ablation of dopaminergic neurons in the VMP had little effect
      on wakefulness. Chemogenetic inhibition of VMP GABAergic neurons also markedly
      increased wakefulness. The wake-promoting effect of the VMP GABAergic neuron
      ablation or inhibition was attenuated to varying degrees by the administration of
      dopamine D1 or D2/3 receptor antagonists and abolished by the administration of
      both antagonists together. In contrast, chemogenetic activation of VMP GABAergic
      neurons very strongly increased slow-wave sleep and reduced wakefulness. These
      findings suggest that VMP GABAergic neurons regulate dopaminergic actions in the
      sleep-wake behavior of mice.SIGNIFICANCE STATEMENT Current understanding of the
      neuronal mechanisms and populations that regulate sleep-wake behavior is
      incomplete. Here, we identified a GABAergic ventral midbrain/pons area that is
      necessary for controlling the daily amount of sleep and wakefulness in mice. We
      also found that these inhibitory neurons control wakefulness by suppressing
      dopaminergic systems. Surprisingly, activation of these neurons strongly induced
      slow-wave sleep while suppressing wakefulness. Our study reveals a new brain
      mechanism critical for sleep-wake regulation.

PMID- 30282731
TI  - Observing Action Sequences Elicits Sequence-Specific Neural Representations in
      Frontoparietal Brain Regions.
AB  - Learning new skills by watching others is important for social and motor
      development throughout the lifespan. Prior research has suggested that
      observational learning shares common substrates with physical practice at both
      cognitive and brain levels. In addition, neuroimaging studies have used
      multivariate analysis techniques to understand neural representations in a
      variety of domains, including vision, audition, memory, and action, but few
      studies have investigated neural plasticity in representational space. Therefore,
      although movement sequences can be learned by observing other people's actions, a
      largely unanswered question in neuroscience is how experience shapes the
      representational space of neural systems. Here, across a sample of male and
      female participants, we combined pretraining and posttraining fMRI sessions with
      6 d of observational practice to determine whether the observation of action
      sequences elicits sequence-specific representations in human frontoparietal brain
      regions and the extent to which these representations become more distinct with
      observational practice. Our results showed that observed action sequences are
      modeled by distinct patterns of activity in frontoparietal cortex and that such
      representations largely generalize to very similar, but untrained, sequences.
      These findings advance our understanding of what is modeled during observational
      learning (sequence-specific information), as well as how it is modeled
      (reorganization of frontoparietal cortex is similar to that previously shown
      following physical practice). Therefore, on a more fine-grained neural level than
      demonstrated previously, our findings reveal how the representational structure
      of frontoparietal cortex maps visual information onto motor circuits in order to
      enhance motor performance.SIGNIFICANCE STATEMENT Learning by watching others is a
      cornerstone in the development of expertise and skilled behavior. However, it
      remains unclear how visual signals are mapped onto motor circuits for such
      learning to occur. Here, we show that observed action sequences are modeled by
      distinct patterns of activity in frontoparietal cortex and that such
      representations largely generalize to very similar, but untrained, sequences.
      These findings advance our understanding of what is modeled during observational
      learning (sequence-specific information), as well as how it is modeled
      (reorganization of frontoparietal cortex is similar to that previously shown
      following physical practice). More generally, these findings demonstrate how
      motor circuit involvement in the perception of action sequences shows high
      fidelity to prior work, which focused on physical performance of action
      sequences.

PMID- 30282730
TI  - Biphasic Modulation of NMDA Receptor Function by Metabotropic Glutamate
      Receptors.
AB  - A recently reported rapid potentiation of NMDA receptors by Group I metabotropic
      glutamate receptors (mGluRIs) via a Homer protein link is distinct from the
      classical, relatively slow inhibitory G-protein-associated signaling triggered by
      mGluRI activation. The relationship between these two mechanisms remains unknown.
      Here, we focused on the mGluRI-dependent modulation of NMDAR response in
      hippocampal dentate gyrus granule cells and cerebellar granule cells of C57BL6-J
      mice and found that these two contrasting mechanisms overlap competitively on the
      time scale from hundreds of milliseconds to seconds, with the net effect
      depending on the cell type. At a shorter time interval (units of millisecond),
      the Homer-mediated signal from mGluRIs prevails, causing upregulation of NMDAR
      function, in both dentate gyrus granule cells and cerebellar granule cells. Our
      results shed light on the possible mechanisms of anti-schizophrenia drugs that
      disrupt Homer-containing protein link.SIGNIFICANCE STATEMENT Here we study
      modulation of NMDA receptors triggered by activation of metabotropic glutamate
      receptors Group I via two distinct pathways: classical G-protein signaling system
      and newly discovered high-speed modulatory mechanism associated with Homer
      protein-containing direct molecular link. We found that these two contrasting
      mechanisms overlap competitively on the time scale from hundreds of milliseconds
      to seconds, with the net effect depending on the cell type. We have also found
      that both crosstalk mechanisms cause significant changes in synaptic strength and
      plasticity. Our results resolve an apparent discrepancy between earlier studies
      that demonstrated contradictive effects of Homer-containing protein link
      disruption on NMDA receptor signaling. On top of that, our data provide a
      plausible explanation for unclear action mechanisms of anti-schizophrenia drugs.

PMID- 30282733
TI  - Nonsaturating large magnetoresistance in semimetals.
AB  - The rapidly expanding class of quantum materials known as topological semimetals
      (TSMs) displays unique transport properties, including a striking dependence of
      resistivity on applied magnetic field, that are of great interest for both
      scientific and technological reasons. So far, many possible sources of
      extraordinarily large nonsaturating magnetoresistance have been proposed.
      However, experimental signatures that can identify or discern the dominant
      mechanism and connect to available theories are scarce. Here we present the
      magnetic susceptibility (chi), the tangent of the Hall angle ([Formula: see
      text]), along with magnetoresistance in four different nonmagnetic semimetals
      with high mobilities, NbP, TaP, NbSb2, and TaSb2, all of which exhibit
      nonsaturating large magnetoresistance (MR). We find that the distinctly different
      temperature dependences, [Formula: see text], and the values of [Formula: see
      text] in phosphides and antimonates serve as empirical criteria to sort the MR
      from different origins: NbP and TaP are uncompensated semimetals with linear
      dispersion, in which the nonsaturating magnetoresistance arises due to guiding
      center motion, while NbSb2 and TaSb2 are compensated semimetals, with a
      magnetoresistance emerging from nearly perfect charge compensation of two
      quadratic bands. Our results illustrate how a combination of magnetotransport and
      susceptibility measurements may be used to categorize the increasingly ubiquitous
      nonsaturating large magnetoresistance in TSMs.

PMID- 30282732
TI  - Abstract Representation of Prospective Reward in the Hippocampus.
AB  - Motivation enhances memory by increasing hippocampal engagement during encoding.
      However, whether such increased hippocampal activation reflects encoding of the
      value of highly rewarding events per se is less understood. Here, using a
      monetary incentive encoding task with a novel manipulation, we tested in humans
      whether the hippocampus represents abstract reward value, independent of
      perceptual content. During functional MRI scanning, men and women studied object
      pairs, each preceded by a monetary reward cue indicating the amount of money they
      would receive if they successfully remembered the object pair at test. Reward
      cues varied on both the level of reward (penny, dime, and dollar) and visual form
      (picture or word) across trials to dissociate hippocampal responses to reward
      value from those reflecting the perceptual properties of the cues. Behaviorally,
      participants remembered pairs associated with the high reward (dollar) more often
      than pairs associated with lower rewards. Neural pattern-similarity analysis
      revealed that hippocampal and parahippocampal cortex activation patterns
      discriminated between cues of different value regardless of their visual form,
      and that hippocampal discrimination of value was most pronounced in participants
      who showed the greatest behavioral sensitivity to reward. Strikingly, hippocampal
      patterns were most distinct for reward cues that differed in value but had
      similar visual appearance, consistent with theoretical proposals of hippocampal
      pattern differentiation of competing representations. Our data illustrate how
      contextual representations within the hippocampus go beyond space and time to
      include information about the motivational salience of events, with hippocampal
      reward coding tracking the motivational impact on later memory.SIGNIFICANCE
      STATEMENT Motivation, such as the promise of future rewards, enhances hippocampal
      engagement during encoding and promotes successful retention of events associated
      with valuable rewards. However, whether the hippocampus explicitly encodes reward
      value, dissociable from sensory information, is unclear. Here, we show that the
      hippocampus forms abstract representation of valuable rewards, encoding
      conceptual rather than perceptual information about the motivational context of
      individual events. Reward representation within the hippocampus is associated
      with preferential retention of high-value events in memory. Furthermore, we show
      that hippocampal-pattern differentiation serves to emphasize differences between
      visually similar events with distinct motivational salience. Collectively, these
      findings indicate that hippocampal contextual representations enable individuals
      to distinguish the motivational value of events, leading to prioritized encoding
      of significant memories.

PMID- 30282734
TI  - Raf kinase inhibitor protein negatively regulates FcepsilonRI-mediated mast cell
      activation and allergic response.
AB  - The signaling cascades triggered by the cross-linkage of immunoglobulin E (IgE)
      with its high-affinity receptor (FcepsilonRI) on mast cells contribute to
      multiple allergic disorders, such as asthma, rhinitis, and atopic dermatitis.
      Restraint of intracellular signals for mast cell activation is essential to
      restore homeostasis. In this study, we found that Raf kinase inhibitor protein
      (RKIP) negatively regulated mast cell activation. RKIP-deficient mast cells
      showed greater IgE-FcepsilonRI-mediated activation than wild-type mast cells.
      Consistently, RKIP deficiency in mast cells rendered mice more sensitive to IgE
      FcepsilonRI-mediated allergic responses and ovalbumin-induced airway
      inflammation. Mechanistically, RKIP interacts with the p85 subunit of PI3K,
      prevents it from binding to GRB2-associated binding protein 2 (Gab2), and
      eventually inhibits the activation of the PI3K/Akt/NF-kappaB complex and its
      downstream signaling. Furthermore, the expression of RKIP was significantly down
      regulated in the peripheral blood of asthma patients and in the IgE-FcepsilonRI
      stimulated mast cells. Collectively, our findings not only suggest that RKIP
      plays an important role in controlling mast cell-mediated allergic responses but
      also provide insight into therapeutic targets for mast cell-related allergic
      diseases.

PMID- 30282735
TI  - The ReFRAME library as a comprehensive drug repurposing library and its
      application to the treatment of cryptosporidiosis.
AB  - The chemical diversity and known safety profiles of drugs previously tested in
      humans make them a valuable set of compounds to explore potential therapeutic
      utility in indications outside those originally targeted, especially neglected
      tropical diseases. This practice of "drug repurposing" has become commonplace in
      academic and other nonprofit drug-discovery efforts, with the appeal that
      significantly less time and resources are required to advance a candidate into
      the clinic. Here, we report a comprehensive open-access, drug repositioning
      screening set of 12,000 compounds (termed ReFRAME; Repurposing, Focused Rescue,
      and Accelerated Medchem) that was assembled by combining three widely used
      commercial drug competitive intelligence databases (Clarivate Integrity, GVK
      Excelra GoStar, and Citeline Pharmaprojects), together with extensive patent
      mining of small molecules that have been dosed in humans. To date, 12,000
      compounds (~80% of compounds identified from data mining) have been purchased or
      synthesized and subsequently plated for screening. To exemplify its utility, this
      collection was screened against Cryptosporidium spp., a major cause of childhood
      diarrhea in the developing world, and two active compounds previously tested in
      humans for other therapeutic indications were identified. Both compounds, VB-201
      and a structurally related analog of ASP-7962, were subsequently shown to be
      efficacious in animal models of Cryptosporidium infection at clinically relevant
      doses, based on available human doses. In addition, an open-access data portal
      (https://reframedb.org) has been developed to share ReFRAME screen hits to
      encourage additional follow-up and maximize the impact of the ReFRAME screening
      collection.

PMID- 30282737
TI  - Oscillatory fluid flow drives scaling of contraction wave with system size.
AB  - Flows over remarkably long distances are crucial to the functioning of many
      organisms, across all kingdoms of life. Coordinated flows are fundamental to
      power deformations, required for migration or development, or to spread resources
      and signals. A ubiquitous mechanism to generate flows, particularly prominent in
      animals and amoebas, is actomyosin cortex-driven mechanical deformations that
      pump the fluid enclosed by the cortex. However, it is unclear how cortex dynamics
      can self-organize to give rise to coordinated flows across the largely varying
      scales of biological systems. Here, we develop a mechanochemical model of
      actomyosin cortex mechanics coupled to a contraction-triggering, soluble
      chemical. The chemical itself is advected with the flows generated by the cortex
      driven deformations of the tubular-shaped cell. The theoretical model predicts a
      dynamic instability giving rise to stable patterns of cortex contraction waves
      and oscillatory flows. Surprisingly, simulated patterns extend beyond the
      intrinsic length scale of the dynamic instability-scaling with system size
      instead. Patterns appear randomly but can be robustly generated in a growing
      system or by flow-generating boundary conditions. We identify oscillatory flows
      as the key for the scaling of contraction waves with system size. Our work shows
      the importance of active flows in biophysical models of patterning, not only as a
      regulating input or an emergent output, but also as a full part of a self
      organized machinery. Contractions and fluid flows are observed in all kinds of
      organisms, so this concept is likely to be relevant for a broad class of systems.

PMID- 30282736
TI  - Postnatal TrkB ablation in corticolimbic interneurons induces social dominance in
      male mice.
AB  - The tight balance between synaptic excitation and inhibition (E/I) within
      neocortical circuits in the mammalian brain is important for complex behavior.
      Many loss-of-function studies have demonstrated that brain-derived neurotrophic
      factor (BDNF) and its cognate receptor tropomyosin receptor kinase B (TrkB) are
      essential for the development of inhibitory GABAergic neurons. However,
      behavioral consequences of impaired BDNF/TrkB signaling in GABAergic neurons
      remain unclear, largely due to confounding motor function deficits observed in
      previous animal models. In this study, we generated conditional knockout mice
      (TrkB cKO) in which TrkB was ablated from a majority of corticolimbic GABAergic
      interneurons postnatally. These mice showed intact motor coordination and
      movement, but exhibited enhanced dominance over other mice in a group-housed
      setting. In addition, immature fast-spiking GABAergic neurons of TrkB cKO mice
      resulted in an E/I imbalance in layer 5 microcircuits within the medial
      prefrontal cortex (mPFC), a key region regulating social dominance. Restoring the
      E/I imbalance via optogenetic modulation in the mPFC of TrkB cKO mice normalized
      their social dominance behavior. Taken together, our results provide strong
      evidence for a role of BDNF/TrkB signaling in inhibitory synaptic modulation and
      social dominance behavior in mice.

PMID- 30282738
TI  - Grid-like hexadirectional modulation of human entorhinal theta oscillations.
AB  - The entorhinal cortex contains a network of grid cells that play a fundamental
      part in the brain's spatial system, supporting tasks such as path integration and
      spatial memory. In rodents, grid cells are thought to rely on network theta
      oscillations, but such signals are not evident in all species, challenging our
      understanding of the physiological basis of the grid network. We analyzed
      intracranial recordings from neurosurgical patients during virtual navigation to
      identify oscillatory characteristics of the human entorhinal grid network. The
      power of entorhinal theta oscillations showed six-fold modulation according to
      the virtual heading during navigation, which is a hypothesized signature of grid
      representations. Furthermore, modulation strength correlated with spatial memory
      performance. These results demonstrate the connection between theta oscillations
      and the human entorhinal grid network and show that features of grid-like
      neuronal representations can be identified from population electrophysiological
      recordings.

PMID- 30282739
TI  - Convergent evolution of complex structures for ant-bacterial defensive symbiosis
      in fungus-farming ants.
AB  - Evolutionary adaptations for maintaining beneficial microbes are hallmarks of
      mutualistic evolution. Fungus-farming "attine" ant species have complex cuticular
      modifications and specialized glands that house and nourish antibiotic-producing
      Actinobacteria symbionts, which in turn protect their hosts' fungus gardens from
      pathogens. Here we reconstruct ant-Actinobacteria evolutionary history across the
      full range of variation within subtribe Attina by combining dated phylogenomic
      and ultramorphological analyses. Ancestral-state analyses indicate the ant
      Actinobacteria symbiosis arose early in attine-ant evolution, a conclusion
      consistent with direct observations of Actinobacteria on fossil ants in Oligo
      Miocene amber. qPCR indicates that the dominant ant-associated Actinobacteria
      belong to the genus Pseudonocardia Tracing the evolutionary trajectories of
      Pseudonocardia-maintaining mechanisms across attine ants reveals a continuum of
      adaptations. In Myrmicocrypta species, which retain many ancestral morphological
      and behavioral traits, Pseudonocardia occur in specific locations on the legs and
      antennae, unassociated with any specialized structures. In contrast, specialized
      cuticular structures, including crypts and tubercles, evolved at least three
      times in derived attine-ant lineages. Conspicuous caste differences in
      Pseudonocardia-maintaining structures, in which specialized structures are
      present in worker ants and queens but reduced or lost in males, are consistent
      with vertical Pseudonocardia transmission. Although the majority of attine ants
      are associated with Pseudonocardia, there have been multiple losses of bacterial
      symbionts and bacteria-maintaining structures in different lineages over
      evolutionary time. The early origin of ant-Pseudonocardia mutualism and the
      multiple evolutionary convergences on strikingly similar anatomical adaptations
      for maintaining bacterial symbionts indicate that Pseudonocardia have played a
      critical role in the evolution of ant fungiculture.

PMID- 30282741
TI  - Private provision of public goods by environmental groups.
AB  - Many environmental nonprofit groups are assumed to provide public goods. While an
      extensive literature examines why donors join and give to nonprofits, none
      directly tests whether donations actually provide public goods. We seek such a
      test by using a common form of environmental organization: watershed groups. We
      find their increased presence resulted in lower dissolved oxygen deficiency and
      higher proportions of swimmable and fishable water bodies. Increased donations to
      and expenditures by the groups also improved water quality. Thus, private groups
      likely played a role in mitigating environmental problems. Overall, our results
      indicate private provision of a public good by nonprofit organizations.

PMID- 30282740
TI  - Intersexual conflict over seed size is stronger in more outcrossed populations of
      a mixed-mating plant.
AB  - In polyandrous species, fathers benefit from attracting greater maternal
      investment toward their offspring at the expense of the offspring of other males,
      while mothers should usually allocate resources equally among offspring. This
      conflict can lead to an evolutionary arms race between the sexes, manifested
      through antagonistic genes whose expression in offspring depends upon the parent
      of origin. The arms race may involve an increase in the strength of maternally
      versus paternally derived alleles engaged in a "tug of war" over maternal
      provisioning or repeated "recognition-avoidance" coevolution where growth
      enhancing paternally derived alleles evolve to escape recognition by maternal
      genes targeted to suppress their effect. Here, we develop predictions to
      distinguish between these two mechanisms when considering crosses among
      populations that have reached different equilibria in this intersexual arms race.
      We test these predictions using crosses within and among populations of
      Dalechampia scandens (Euphorbiaceae) that presumably have experienced different
      intensities of intersexual conflict, as inferred from their historical
      differences in mating system. In crosses where the paternal population was more
      outcrossed than the maternal population, hybrid seeds were larger than those
      normally produced in the maternal population, whereas when the maternal
      population was more outcrossed, hybrid seeds were smaller than normal. These
      results confirm the importance of mating systems in determining the intensity of
      intersexual conflict over maternal investment and provide strong support for a
      tug-of-war mechanism operating in this conflict. They also yield clear
      predictions for the fitness consequences of gene flow among populations with
      different mating histories.

PMID- 30282742
TI  - Intergroup social influence on emotion processing in the brain.
AB  - Emotions usually occur in a social context; yet little is known about how similar
      and dissimilar others influence our emotions. In the current study, we examined
      whether ingroup and outgroup members have differential influence on emotion
      processing at the behavioral and neural levels. To this end, we recruited 45
      participants to rate a series of images displaying people engaged in different
      emotional contexts. Participants then underwent an fMRI scan where they viewed
      the same images along with information on how ingroup and outgroup members rated
      them, and they were asked to rate the images again. We found that participants
      shifted their emotions to be more in alignment with the ingroup over the
      outgroup, and that neural regions implicated in positive valuation [ventral
      striatum (VS) and ventromedial prefrontal cortex (vmPFC)], mentalizing
      [dorsomedial prefrontal cortex (dmPFC), medial prefrontal cortex (mPFC),
      posterior superior temporal sulcus (pSTS), and temporal pole], as well as emotion
      processing and salience detection (amygdala and insula), linearly tracked this
      behavior such that the extent of neural activity in these regions paralleled
      changes in participants' emotions. Results illustrate the powerful impact that
      ingroup members have on our emotions.

PMID- 30282743
TI  - Left/right asymmetric collective migration of parapineal cells is mediated by
      focal FGF signaling activity in leading cells.
AB  - The ability of cells to collectively interpret surrounding environmental signals
      underpins their capacity to coordinate their migration in various contexts,
      including embryonic development and cancer metastasis. One tractable model for
      studying collective migration is the parapineal, a left-sided group of neurons
      that arises from bilaterally positioned precursors that undergo a collective
      migration to the left side of the brain. In zebrafish, the migration of these
      cells requires Fgf8 and, in this study, we resolve how FGF signaling correlates
      with-and impacts the migratory dynamics of-the parapineal cell collective. The
      temporal and spatial dynamics of an FGF reporter transgene reveal that FGF
      signaling is activated in only few parapineal cells usually located at the
      leading edge of the parapineal during its migration. Overexpressing a
      constitutively active Fgf receptor compromises parapineal migration in wild-type
      embryos, while it partially restores both parapineal migration and mosaic
      expression of the FGF reporter transgene in fgf8 -/- mutant embryos. Focal
      activation of FGF signaling in few parapineal cells is sufficient to promote the
      migration of the whole parapineal collective. Finally, we show that asymmetric
      Nodal signaling contributes to the restriction and leftwards bias of FGF pathway
      activation. Our data indicate that the first overt morphological asymmetry in the
      zebrafish brain is promoted by FGF pathway activation in cells that lead the
      collective migration of the parapineal to the left. This study shows that cell
      state differences in FGF signaling in front versus rear cells is required to
      promote migration in a model of FGF-dependent collective migration.

PMID- 30282745
TI  - Blue carbon: past, present and future, with emphasis on macroalgae.
AB  - Blue carbon did not originally include macroalgal ecosystems; however evidence is
      mounting that macroalgal ecosystems function in marine carbon sequestration. The
      great majority of present day marine macroalgal net primary productivity (NPP)
      involves haptophytic algae on eroding shores. For these organisms the long-term
      storage of particulate organic carbon involves export from the site of production
      of biomass that has evaded parasites and grazers, and that some of the exported
      biomass is sedimented and stored rather than being mineralized en route by
      detritivores (microbes and fauna). Export from eroding shores, and subsequent
      storage, of haptophytic marine macroalgal particulate organic carbon could have
      started by 1.6 Ga. Storage on depositing shores close to the site of NPP by
      rhizophytic macroalgae and then by rhizophytic coastal seagrasses, tidal marshes
      and mangroves began not less than 209 Ma ago. Future increases in surface ocean
      temperatures may bring tropical marine macroalgae to their upper temperature
      limit, while temperate marine macroalgae will migrate poleward, in both cases
      assuming that temperature increases faster than genetic adaptation to higher
      temperature. Increased CO2 in the surface ocean will generally favour uncalcified
      over calcified marine macroalgae. This results in decreased CO2 release from
      decreased calcification, as well as decreased ballasting by CaCO3 of exported
      particulate organic carbon resulting in decreasing sedimentation. While much more
      work is needed, the available information suggests that macroalgae play a
      significant role in marine organic carbon storage.

PMID- 30282746
TI  - Is callose required for silicification in plants?
AB  - The cell wall polymer callose catalyses the formation of silica in vitro and is
      heavily implicated in biological silicification in Equisetum (horsetail) and
      Arabidopsis (thale cress) in vivo Callose, a beta-1,3-glucan, is an ideal partner
      for silicification, because its amorphous structure and ephemeral nature provide
      suitable microenvironments to support the condensation of silicic acid into
      silica. Herein, using scanning electron microscopy, immunohistochemistry and
      fluorescence, we provide further evidence of the cooperative nature of callose
      and silica in biological silicification in rice, an important crop plant and
      known silica accumulator. These new data along with recently published research
      enable us to propose a model to describe the intracellular events that together
      determine callose-driven biological silicification.

PMID- 30282744
TI  - Abscisic acid-independent stomatal CO2 signal transduction pathway and
      convergence of CO2 and ABA signaling downstream of OST1 kinase.
AB  - Stomatal pore apertures are narrowing globally due to the continuing rise in
      atmospheric [CO2]. CO2 elevation and the plant hormone abscisic acid (ABA) both
      induce rapid stomatal closure. However, the underlying signal transduction
      mechanisms for CO2/ABA interaction remain unclear. Two models have been
      considered: (i) CO2 elevation enhances ABA concentrations and/or early ABA
      signaling in guard cells to induce stomatal closure and (ii) CO2 signaling merges
      with ABA at OST1/SnRK2.6 protein kinase activation. Here we use genetics, ABA
      reporter imaging, stomatal conductance, patch clamp, and biochemical analyses to
      investigate these models. The strong ABA biosynthesis mutants nced3/nced5 and
      aba2-1 remain responsive to CO2 elevation. Rapid CO2-triggered stomatal closure
      in PYR/RCAR ABA receptor quadruple and hextuple mutants is not disrupted but
      delayed. Time-resolved ABA concentration monitoring in guard cells using a FRET
      based ABA-reporter, ABAleon2.15, and ABA reporter gene assays suggest that CO2
      elevation does not trigger [ABA] increases in guard cells, in contrast to control
      ABA exposures. Moreover, CO2 activates guard cell S-type anion channels in
      nced3/nced5 and ABA receptor hextuple mutants. Unexpectedly, in-gel protein
      kinase assays show that unlike ABA, elevated CO2 does not activate OST1/SnRK2
      kinases in guard cells. The present study points to a model in which rapid CO2
      signal transduction leading to stomatal closure occurs via an ABA-independent
      pathway downstream of OST1/SnRK2.6. Basal ABA signaling and OST1/SnRK2 activity
      are required to facilitate the stomatal response to elevated CO2 These findings
      provide insights into the interaction between CO2/ABA signal transduction in
      light of the continuing rise in atmospheric [CO2].

PMID- 30282747
TI  - Fish in habitats with higher motorboat disturbance show reduced sensitivity to
      motorboat noise.
AB  - Anthropogenic noise can negatively impact many taxa worldwide. It is possible
      that in noisy, high-disturbance environments, the range and severity of impacts
      could diminish over time, but the influence of previous disturbance remains
      untested in natural conditions. This study demonstrates the effects of motorboat
      noise on the physiology of an endemic cichlid fish in Lake Malawi. Exposure to
      motorboats (driven 20-100 m from fish) and loudspeaker playback of motorboat
      noise both elevated the oxygen-consumption rate at a single lower-disturbance
      site, characterized by low historic and current motorboat activity. Repeating
      this assay at further lower-disturbance sites revealed a consistent effect of
      elevated oxygen consumption in response to motorboat disturbance. However, when
      similar trials were repeated at four higher-disturbance sites, no effect of
      motorboat exposure was detected. These results demonstrate that disturbance
      history can affect local population responses to noise. Action regarding noise
      pollution should consider the past, as well as the present, when planning for the
      future.

PMID- 30282748
TI  - Phylogenetic non-independence in rates of trait evolution.
AB  - Statistical non-independence of species' biological traits is recognized in most
      traits under selection. Yet, whether or not the evolutionary rates of such
      biological traits are statistically non-independent remains to be tested. Here,
      we test the hypothesis that phenotypic evolutionary rates are non-independent,
      i.e. contain phylogenetic signal, using empirical rates of evolution in three
      separate traits: body mass in mammals, beak shape in birds and bite force in
      amniotes. Specifically, we test if evolutionary rates are phylogenetically
      interdependent. We find evidence for phylogenetic signal in evolutionary rates in
      all three case studies. While phylogenetic signal diminishes deeper in time, this
      is reflective of statistical power owing to small sample and effect sizes. When
      effect size is large, e.g. owing to the presence of fossil tips, we detect high
      phylogenetic signals even in deeper time slices. Thus, we recommend that rates be
      treated as being non-independent throughout the evolutionary history of the group
      of organisms under study, and any summaries or analyses of rates through time
      including associations of rates with traits-need to account for the undesired
      effects of shared ancestry.

PMID- 30282749
TI  - HIV-1 Nef Hijacks Lck and Rac1 Endosomal Traffic To Dually Modulate Signaling
      Mediated and Actin Cytoskeleton-Mediated T Cell Functions.
AB  - Endosomal traffic of TCR and signaling molecules regulates immunological synapse
      formation and T cell activation. We recently showed that Rab11 endosomes regulate
      the subcellular localization of the tyrosine kinase Lck and of the GTPase Rac1
      and control their functions in TCR signaling and actin cytoskeleton remodeling.
      HIV-1 infection of T cells alters their endosomal traffic, activation capacity,
      and actin cytoskeleton organization. The viral protein Nef is pivotal for these
      modifications. We hypothesized that HIV-1 Nef could jointly alter Lck and Rac1
      endosomal traffic and concomitantly modulate their functions. In this study, we
      show that HIV-1 infection of human T cells sequesters both Lck and Rac1 in a
      pericentrosomal compartment in an Nef-dependent manner. Strikingly, the Nef
      induced Lck compartment contains signaling-competent forms (phosphorylated on key
      Tyr residues) of Lck and some of its downstream effectors, TCRzeta, ZAP70, SLP76,
      and Vav1, avoiding the proximal LAT adaptor. Importantly, Nef-induced
      concentration of signaling molecules was concomitant with the upregulation of
      several early and late T cell activation genes. Moreover, preventing the
      concentration of the Nef-induced Lck compartment by depleting the Rab11 effector
      FIP3 counteracted Nef-induced gene expression upregulation. In addition, Nef
      extensively sequesters Rac1 and downregulates Rac1-dependent actin cytoskeleton
      remodeling, thus reducing T cell spreading. Therefore, by modifying their
      endosomal traffic, Nef hijacks signaling and actin cytoskeleton regulators to
      dually modulate their functional outputs. Our data shed new light into the
      molecular mechanisms that modify T cell physiology during HIV-1 infection.

PMID- 30282750
TI  - B Cell-Intrinsic STING Signaling Triggers Cell Activation, Synergizes with B Cell
      Receptor Signals, and Promotes Antibody Responses.
AB  - Generation of protective immune responses requires coordinated stimulation of
      innate and adaptive immune responses. An important mediator of innate immunity is
      stimulator of IFN genes (STING, MPYS, MITA), a ubiquitously but differentially
      expressed adaptor molecule that functions in the relay of signals initiated by
      sensing of cytosolic DNA and bacterial cyclic dinucleotides (CDNs). Whereas
      systemic expression of STING is required for CDN-aided mucosal Ab responses, its
      function in B cells in particular is unclear. In this study, we show that B cells
      can be directly activated by CDNs in a STING-dependent manner in vitro and in
      vivo. Direct activation of B cells by CDNs results in upregulation of
      costimulatory molecules and cytokine production and this can be accompanied by
      caspase-dependent cell death. CDN-induced cytokine production by B cells and
      other cell types also contributes to activation and immune responses. Type I IFN
      is primarily responsible for this indirect stimulation although other cytokines
      may contribute. BCR and STING signaling pathways act synergistically to promote
      Ab responses independent of type I IFN. B cell expression of STING is required
      for optimal in vivo IgG and mucosal IgA Ab responses induced by T cell-dependent
      Ags and cyclic-di-GMP but plays no discernable role in Ab responses in which alum
      is used as an adjuvant. Thus, STING functions autonomously in B cells responding
      to CDNs, and its activation synergizes with Ag receptor signals to promote B cell
      activation.

PMID- 30282752
TI  - VASP Regulates NK Cell Lytic Granule Convergence.
AB  - NK cells eliminate viral-infected and malignant cells through a highly
      orchestrated series of cytoskeletal rearrangements, resulting in the release of
      cytolytic granule contents toward the target cell. Central to this process is the
      convergence of cytolytic granules to a common point, the microtubule-organizing
      center (MTOC), before delivery to the synapse. In this study, we show that
      vasodialator-stimulated phosphoprotein (VASP), an actin regulatory protein,
      localizes to the cytolytic synapse, but surprisingly, shows no impact on
      conjugate formation or synaptic actin accumulation despite being required for
      human NK cell-mediated killing. Interestingly, we also find that a pool of VASP
      copurifies with lytic granules and localizes with lytic granules at the MTOC.
      Significantly, depletion of VASP decreased lytic granule convergence without
      impacting MTOC polarization. Using the KHYG-1 cell line in which lytic granules
      are in a constitutively converged state, we find that either VASP depletion or F
      actin destabilization promoted spreading of formerly converged granules. Our
      results demonstrate a novel requirement for VASP and actin polymerization in
      maintaining lytic granule convergence during NK cell-mediated killing.

PMID- 30282751
TI  - IL-2/CD25: A Long-Acting Fusion Protein That Promotes Immune Tolerance by
      Selectively Targeting the IL-2 Receptor on Regulatory T Cells.
AB  - Low-dose IL-2 represents an immunotherapy to selectively expand regulatory T
      cells (Tregs) to promote tolerance in patients with autoimmunity. In this
      article, we show that a fusion protein (FP) of mouse IL-2 and mouse IL-2Ralpha
      (CD25), joined by a noncleavable linker, has greater in vivo efficacy than rIL-2
      at Treg expansion and control of autoimmunity. Biochemical and functional studies
      support a model in which IL-2 interacts with CD25 in the context of this FP in
      trans to form inactive head-to-tail dimers that slowly dissociate into an active
      monomer. In vitro, IL-2/CD25 has low sp. act. However, in vivo IL-2/CD25 is long
      lived to persistently and selectively stimulate Tregs. In female NOD mice, IL
      2/CD25 administration increased Tregs within the pancreas and reduced the
      instance of spontaneous diabetes. Thus, IL-2/CD25 represents a distinct class of
      IL-2 FPs with the potential for clinical development for use in autoimmunity or
      other disorders of an overactive immune response.

PMID- 30282753
TI  - A Novel Neutralizing Antibody Specific to the DE Loop of VP1 Can Inhibit EV-D68
      Infection in Mice.
AB  - Enterovirus D68 (EV-D68) belongs to the picornavirus family and was first
      isolated in CA, USA, in 1962. EV-D68 can cause severe cranial nerve system damage
      such as flaccid paralysis and acute respiratory diseases such as pneumonia. There
      are currently no efficient therapeutic methods or effective prophylactics. In
      this study, we isolated the mAb A6-1 from an EV-D68-infected rhesus macaque
      (Macaca mulatta) and found that the Ab provided effective protection in EV-D68
      intranasally infected suckling mice. We observed that A6-1 bound to the DE loop
      of EV-D68 VP1 and interfered with the interaction between the EV-D68 virus and
      alpha2,6-linked sialic acids of the host cell. The production of A6-1 and its Ab
      properties present a bridging study for EV-D68 vaccine design and provide a tool
      for analyzing the process by which Abs can inhibit EV-D68 infection.

PMID- 30282754
TI  - Use of a meta-research team to facilitate evidence-based medicine to the next
      generation.

PMID- 30282757
TI  - Bawa-Garba case: GMC failed in its job as a regulator.

PMID- 30282758
TI  - Pathogen evolution in finite populations: slow and steady spreads the best.
AB  - The theory of life-history evolution provides a powerful framework to understand
      the evolutionary dynamics of pathogens. It assumes, however, that host
      populations are large and that one can neglect the effects of demographic
      stochasticity. Here, we expand the theory to account for the effects of finite
      population size on the evolution of pathogen virulence. We show that demographic
      stochasticity introduces additional evolutionary forces that can qualitatively
      affect the dynamics and the evolutionary outcome. We discuss the importance of
      the shape of the pathogen fitness landscape on the balance between mutation,
      selection and genetic drift. This analysis reconciles Adaptive Dynamics with
      population genetics in finite populations and provides a new theoretical toolbox
      to study life-history evolution in realistic ecological scenarios.

PMID- 30282755
TI  - A Computational Modeling Approach Predicts Interaction of the Antifungal Protein
      AFP from Aspergillus giganteus with Fungal Membranes via Its gamma-Core Motif.
AB  - Fungal pathogens kill more people per year globally than malaria or tuberculosis
      and threaten international food security through crop destruction. New
      sophisticated strategies to inhibit fungal growth are thus urgently needed. Among
      the potential candidate molecules that strongly inhibit fungal spore germination
      are small cationic, cysteine-stabilized proteins of the AFP family secreted by a
      group of filamentous Ascomycetes. Its founding member, AFP from Aspergillus
      giganteus, is of particular interest since it selectively inhibits the growth of
      filamentous fungi without affecting the viability of mammalian, plant, or
      bacterial cells. AFPs are also characterized by their high efficacy and
      stability. Thus, AFP can serve as a lead compound for the development of novel
      antifungals. Notably, all members of the AFP family comprise a gamma-core motif
      which is conserved in all antimicrobial proteins from pro- and eukaryotes and
      known to interfere with the integrity of cytoplasmic plasma membranes. In this
      study, we used classical molecular dynamics simulations combined with wet
      laboratory experiments and nuclear magnetic resonance (NMR) spectroscopy to
      characterize the structure and dynamical behavior of AFP isomers in solution and
      their interaction with fungal model membranes. We demonstrate that the gamma-core
      motif of structurally conserved AFP is the key for its membrane interaction, thus
      verifying for the first time that the conserved gamma-core motif of antimicrobial
      proteins is directly involved in protein-membrane interactions. Furthermore,
      molecular dynamic simulations suggested that AFP does not destroy the fungal
      membrane by pore formation but covers its surface in a well-defined manner, using
      a multistep mechanism to destroy the membranes integrity.IMPORTANCE Fungal
      pathogens pose a serious danger to human welfare since they kill more people per
      year than malaria or tuberculosis and are responsible for crop losses worldwide.
      The treatment of fungal infections is becoming more complicated as fungi develop
      resistances against commonly used fungicides. Therefore, discovery and
      development of novel antifungal agents are of utmost importance.

PMID- 30282760
TI  - RT-QuIC: a new test for sporadic CJD.
AB  - The diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) can be difficult, but
      the real-time quaking-induced conversion (RT-QuIC) assays have made a
      considerable impact on its clinical diagnosis. This technique exploits the
      ability of the misfolded pathological form of prion protein (PrPSc) found in
      cerebrospinal fluid (CSF) to induce conversion of normal PrP to the misfolded
      form, which subsequently aggregates. The formation of these aggregates of
      misfolded PrP is monitored in real time using fluorescent dyes. The current
      sensitivity of CSF RT-QuIC undertaken at the UK National CJD Research &
      Surveillance Unit is 92% and the specificity is 100%. The interpretation of the
      RT-QuIC traces is affected by the presence of raised CSF red and white cells
      counts and elevated total protein concentrations. We recommend that CSF samples
      for RT-QuIC analysis are clear and colourless with a white cell count of <10
      x10^6/L and have a total protein concentration of <1 g/L.

PMID- 30282756
TI  - Highly Reduced Genome of the New Species Mycobacterium uberis, the Causative
      Agent of Nodular Thelitis and Tuberculoid Scrotitis in Livestock and a Close
      Relative of the Leprosy Bacilli.
AB  - Nodular thelitis is a chronic enzootic infection affecting dairy cows and goats.
      The causative agent was recently shown to be related to the leprosy-causing
      bacilli Mycobacterium leprae and Mycobacterium lepromatosis In this study, the
      genome of this pathogen was sequenced and analyzed. Phylogenomic analyses
      confirmed that the pathogen present in nodular thelitis and tuberculoid scrotitis
      is a distinct species related to the leprosy bacilli and Mycobacterium
      haemophilum Because the pathogen was originally isolated from a bovine udder, it
      was named "Mycobacterium uberis" The genome of "M. uberis" is only 3.12 Mb in
      length, which represents the smallest mycobacterial genome identified so far but
      which is close to that of leprosy bacilli in size. The genome contains 1,759
      protein-coding genes and 1,081 pseudogenes, indicative of extensive reductive
      evolution and likely the reason that M. uberis cannot be grown axenically. The
      pseudogenization and genome reduction in M. uberis seem to have been to some
      extent independent from the results determined for the genomes of the leprosy
      bacilli.IMPORTANCE M. uberis is an emerging skin pathogen in dairy animals. Its
      genome underwent massive reduction and gene decay, leading to a minimal set of
      genes required for an obligatory intracellular lifestyle, which highly resembles
      the evolution of the leprosy agents M. leprae and M. lepromatosis The genomic
      similarity between M. uberis and the leprosy bacilli can help in identifying key
      virulence factors of these closely related species or in identifying genes
      responsible for the distinct differences between thelitis or scrotitis and
      leprosy with respect to clinical manifestations. Specific DNA markers can now be
      developed for quick detection of this pathogen.

PMID- 30282759
TI  - Lessons from pressure denaturation of proteins.
AB  - Although it is now relatively well understood how sequence defines and impacts
      global protein stability in specific structural contexts, the question of how
      sequence modulates the configurational landscape of proteins remains to be
      defined. Protein configurational equilibria are generally characterized by using
      various chemical denaturants or by changing temperature or pH. Another
      thermodynamic parameter which is less often used in such studies is high
      hydrostatic pressure. This review discusses the basis for pressure effects on
      protein structure and stability, and describes how the unique mechanisms of
      pressure-induced unfolding can provide unique insights into protein
      conformational landscapes.

PMID- 30282761
TI  - Better quality of care equals better carbon footprint?

PMID- 30282762
TI  - Neurocysticercosis: mimics and chameleons.
AB  - Neurocysticercosis is the most common parasitic neurological disease worldwide,
      yet in Europe, it remains relatively uncommon, with many practitioners rarely
      seeing a case. However, immigration and international travel mean that it is
      becoming increasingly recognised and diagnosed in developed countries. Being a
      treatable condition, it is essential to be familiar with the diagnosis and to
      appreciate its mimics and breadth of its possible clinical presentations.

PMID- 30282763
TI  - Can compressive thoracic cord lesions cause a pure lower motor neurone syndrome?
AB  - Compressive lesions of the spinal cord usually cause a syndrome of upper motor
      neurone weakness, spasticity and sensory loss below the level of the lesion. It
      has long been recognised that compressive cervical cord lesions may present as
      isolated lower motor neurone weakness of the upper limbs, a syndrome termed
      cervical spondylotic amyotrophy. We describe two patients presenting with
      isolated lower motor neurone weakness of the lower limbs in association with a
      compressive cord lesion at T11/12, a condition we have termed thoracic
      spondylotic amyotrophy.

PMID- 30282764
TI  - Lyme disease: diagnosis and management.
AB  - Lyme disease (borreliosis) is a tick-borne bacterial infection caused by the
      spirochaete Borrelia burgdoferi, transmitted by hard-backed Ixodes ticks. Actual
      numbers of cases are increasing and it appears that the distribution across the
      UK is widening; however, it occurs most frequently in area of woodland, with
      temperate climate. It typically presents in mid to late summer. Lyme disease is a
      multisystem disease. The nervous system is the second most commonly affected
      system after the skin. Other systemic manifestations, such as carditis,
      keratitis, uveitis and inflammatory arthritis, rarely occur in European Lyme
      disease. In 2018, the National Institute for Health and Care Excellence has
      updated its guidelines on the diagnosis and management of Lyme disease. Here, we
      highlight important aspects of this guidance and provide a more detailed review
      of the clinical spectrum of neuroborreliosis, illustrated by cases we have seen.

PMID- 30282766
TI  - Evidence based versus defensive medicine.

PMID- 30282765
TI  - Cities for global health.

PMID- 30282767
TI  - The road to quality: Paved with more than good intentions.

PMID- 30282768
TI  - Neuronal intranuclear inclusion disease showing intranuclear inclusions in renal
      biopsy 12 years earlier.

PMID- 30282769
TI  - Sleep duration and risk of incident stroke by age, sex, and race: The REGARDS
      study.
AB  - OBJECTIVE: To investigate the association between reported sleep duration and
      incident stroke in a US cohort of black and white adults, and evaluate race, age,
      and sex as potential effect modifiers. METHODS: From 2008 to 2010, 16,733 black
      and white adults, aged >=45 years, without a history of stroke or sleep
      disordered breathing from the Reasons for Geographic and Racial Differences in
      Stroke (REGARDS) study, reported their habitual sleep duration (<6, 6.0-6.9, 7.0
      8.9 [reference], >=9 hours). Incident strokes were identified through biannual
      participant contact followed by physician adjudication of medical records. Cox
      proportional hazards analysis was conducted to calculate hazard ratios of
      interactions between sleep duration with race, age, sex, and 2-way combinations
      of these factors on incident stroke adjusting for stroke risk factors and sleep
      disordered breathing risk. RESULTS: The sample comprised 10.4% (n = 1,747) short
      sleepers (<6 hours) and 6.8% (n = 1,134) long sleepers (>=9 hours). Over an
      average 6.1 years follow-up, 460 strokes occurred. There were significant
      interactions between sleep duration and race (p = 0.018) and sleep duration and
      race-sex groups (p = 0.0023) in association with incident stroke. Short sleep
      duration was significantly associated with decreased risk for stroke among black
      participants (hazard ratio [HR] 0.49 [95% confidence interval (CI) 0.28-0.85]),
      particularly black men (HR 0.21 [95% CI 0.07-0.69]), whereas long sleep duration
      was significantly associated with increased risk for stroke among white men (HR
      1.71 [95% CI 1.06-2.76]). CONCLUSIONS: The association of sleep duration with
      incident stroke differs by race and sex, with short sleep duration among black
      men associated with decreased risk, whereas long sleep duration among white men
      associated with increased risk for stroke.

PMID- 30282770
TI  - Racial differences in recurrent ischemic stroke risk and recurrent stroke case
      fatality.
AB  - OBJECTIVE: To determine black-white differences in 1-year recurrent stroke and 30
      day case fatality after a recurrent stroke in older US adults. METHODS: We
      conducted a retrospective cohort study using a 5% random sample of Medicare
      beneficiaries with fee-for-service health insurance coverage who were
      hospitalized for ischemic stroke between 1999 and 2013. Hazard ratios for
      recurrent ischemic stroke and risk ratios for 30-day case fatality comparing
      blacks to whites were calculated with adjustment for demographics, risk factors,
      and competing risk of death when appropriate. RESULTS: Among 128,789 Medicare
      beneficiaries having an ischemic stroke (mean age 80 years [SD 8 years], 60.4%
      male), 11.1% were black. The incidence rate of recurrent ischemic stroke per
      1,000 person-years for whites and blacks was 108 (95% confidence interval [CI],
      106-111) and 154 (95% CI 147-162) , respectively. The multivariable-adjusted
      hazard ratio for recurrent stroke among blacks compared with whites was 1.36 (95%
      CI 1.29-1.44). The case fatality after recurrent stroke for blacks and whites was
      21% (95% CI 21%-22%) and 16% (95% CI 15%-18%), respectively. The multivariable
      adjusted relative risk for mortality within 30 days of a recurrent stroke among
      blacks compared with whites was 0.82 (95% CI 0.73-0.93). CONCLUSION: The risk of
      stroke recurrence among older Americans hospitalized for ischemic stroke is
      higher for blacks compared to whites, while 30-day case fatality after recurrent
      stroke remains lower for blacks.

PMID- 30282772
TI  - Imbalance of cortical facilitatory and inhibitory circuits underlies
      hyperexcitability in ALS.
AB  - OBJECTIVE: To determine the relative contribution of inhibitory and facilitatory
      circuits in the development of cortical hyperexcitability in amyotrophic lateral
      sclerosis (ALS). METHODS: In this cross-sectional study, cortical excitability
      was assessed in 27 patients with ALS, and results compared to 25 healthy
      controls. In addition, a novel neurophysiologic measure of cortical function,
      short-interval intracortical facilitation (SICF), was assessed reflecting
      activity of the facilitatory circuits. RESULTS: There was a significant increase
      in SICF (ALS -18.51 +/- 1.56%, controls -8.52 +/- 1.21%, p < 0.001) in patients
      with ALS that was accompanied by a reduction of short-interval intracortical
      inhibition (ALS 3.94 +/- 1.29%, controls 14.23 +/- 1.18%, p < 0.001) and cortical
      silent period duration (p = 0.034). The index of excitation, a biomarker
      reflecting the contribution of inhibitory and facilitatory circuit activity, was
      significantly increased in patients with ALS (82.79 +/- 6.01%) compared to
      controls (36.15 +/- 3.44, p < 0.001), suggesting a shift toward cortical
      excitation. Increased excitation correlated with upper motor neuron signs (R 2 =
      0.235, p = 0.016) and greater functional disability as reflected by a correlation
      with the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score (R 2
      = 0.335, p = 0.002). CONCLUSIONS: The present study established that cortical
      hyperexcitability is a key contributor to ALS pathophysiology, mediated through
      dysfunction of inhibitory and facilitatory intracortical circuits. Therapies
      aimed at restoring the cortical inhibitory imbalance provide novel avenues for
      future therapeutic targets.

PMID- 30282771
TI  - Paraneoplastic neuronal intermediate filament autoimmunity.
AB  - OBJECTIVE: To describe paraneoplastic neuronal intermediate filament (NIF)
      autoimmunity. METHODS: Archived patient and control serum and CSF specimens were
      evaluated by tissue-based indirect immunofluorescence assay (IFA). Autoantigens
      were identified by Western blot and mass spectrometry. NIF specificity was
      confirmed by dual tissue section staining and 5 recombinant NIF-specific HEK293
      cell-based assays (CBAs, for alpha-internexin, neurofilament light [NfL],
      neurofilament medium, or neurofilament heavy chain, and peripherin). NIF
      immunoglobulin Gs (IgGs) were correlated with neurologic syndromes and cancers.
      RESULTS: Among 65 patients, NIF-IgG-positive by IFA and CBAs, 33 were female
      (51%). Median symptom onset age was 62 years (range 18-88). Patients fell into 2
      groups, defined by the presence of NfL-IgG (21 patients, who mostly had >=4 NIF
      IgGs detected) or its absence (44 patients, who mostly had <=2 NIF-IgGs
      detected). Among NfL-IgG-positive patients, 19/21 had >=1 subacute onset CNS
      disorders: cerebellar ataxia (11), encephalopathy (11), or myelopathy (2).
      Cancers were detected in 16 of 21 patients (77%): carcinomas of neuroendocrine
      lineage (10) being most common (small cell [5], Merkel cell [3], other
      neuroendocrine [2]). Two of 257 controls (0.8%, both with small cell carcinoma)
      were positive by both IFA and CBA. Five of 7 patients with immunotherapy data
      improved. By comparison, the 44 NfL-IgG-negative patients had findings of unclear
      significance: diverse nervous system disorders (p = 0.006), as well as limited (p
      = 0.003) and more diverse (p < 0.0001) cancer accompaniments. CONCLUSIONS: NIF
      IgG detection by IFA, with confirmatory CBA testing that yields a profile
      including NfL-IgG, defines a paraneoplastic CNS disorder (usually ataxia or
      encephalopathy) accompanying neuroendocrine lineage neoplasia.

PMID- 30282773
TI  - Quality improvement in neurology: Epilepsy Quality Measurement Set 2017 update.

PMID- 30282774
TI  - Young adult susceptible non-smokers' and smokers' responses to capsule
      cigarettes.
AB  - BACKGROUND: Flavour capsule cigarette variants (FCVs), which allow users to
      customise their smoking experience and reduce the harshness of smoking, have
      captured an increasing share of many markets. We examined tobacco companies'
      argument that such product innovations aim simply to shift market share, by
      estimating smokers' and susceptible non-smokers' responses to FCVs. METHODS: We
      conducted an online survey of 425 smokers (daily and non-daily), susceptible non
      smokers (n=224) and former smokers (n=166) aged between 18 and 25. Restrpondents
      completed a choice experiment, a behavioural probability measure and a perception
      task. We analysed the choice data using a conditional logistic regression and a
      rank-ordered logistic regression, and the probability and perception data using t
      tests and descriptive statistics. RESULTS: Non-smokers preferred an FCV relative
      to an unflavoured cigarette, whereas the opposite was the case for smokers.
      Susceptible non-smokers and former smokers were more likely to try a fruit
      flavoured FCV than an unflavoured stick, while daily smokers were more likely
      than non-daily smokers to do the same. Susceptible non-smokers, former smokers
      and non-daily smokers also had more positive perceptions of FCVs relative to
      unflavoured sticks than did daily smokers. CONCLUSIONS: FCVs appeal more to non
      smokers than to smokers, and more to non-daily smokers than to daily smokers.
      They thus appear likely to recruit non-smokers and potentially increase overall
      smoking prevalence. Policy responses include ensuring standardised packaging
      legislation disallows FCVs by specifically regulating the appearance and design
      of tobacco products, or introducing bespoke regulation that addresses the threat
      posed by FCVs.

PMID- 30282775
TI  - Basic economic gap related to smoking: reconciling tobacco tax receipts and
      economic costs of smoking-attributable diseases.
AB  - BACKGROUND: Tobacco tax rates set by various governments are not based on the
      idea that tax receipts should cover the costs incurred by smoking. It can be
      assumed that tobacco tax receipts (TTR) differ from the costs of smoking. The aim
      is to determine the global basic economic gap (BEG) between TTR and the economic
      costs of smoking-attributable diseases (ECS). METHODS: BEG is described as the
      difference between the ECS and TTR. A total of 124 countries representing 94% of
      global tobacco consumption were included in the research by means of the creation
      of a database, the adjustment of input data and the identification of their
      intersection. RESULTS: The global BEG reaches US$1438 billion per year. The
      global ECS are US$1911 billion per year. The global TTR are US$473 billion per
      year and compensate for only one quarter of the ECS. Within countries with the
      highest consumption of cigarettes, especially the USA but also Russia and
      Germany, the proportion of the ECS covered by the TTR is even lower, although
      private health expenditures have been taken into account. CONCLUSIONS: Our
      findings suggest that tobacco taxes would have to be globally increased by more
      than four times on average in order to cover the ECS or between two and two-and-a
      half times if we take private health expenditures into account. The informational
      pressure concerning health risks associated with smoking aimed at reducing
      harmful consumption and improving global health can also be supported with these
      economic facts.

PMID- 30282776
TI  - Quantifying homologous proteins and proteoforms.
AB  - Many proteoforms - arising from alternative splicing, post-translational
      modifications (PTM), or paralogous genes - have distinct biological functions,
      such as histone PTM proteoforms. However, their quantification by existing bottom
      up mass-spectrometry (MS) methods is undermined by peptide-specific biases. To
      avoid these biases, we developed and implemented a first-principles model
      (HIquant ) for quantifying proteoform stoichiometries. We characterized when MS
      data allow inferring proteoform stoichiometries by HIquant and derived an
      algorithm for optimal inference. We applied this algorithm to infer proteoform
      stoichiometries in two experimental systems that supported rigorous bench
      marking: alkylated proteoforms spiked-in at known ratios and endogenous histone 3
      PTM proteoforms quantified relative to internal heavy standards. When compared to
      the benchmarks, the proteoform stoichiometries interfered by HIquant without
      using external standards had relative error of 5 - 15% for simple proteoforms and
      20 - 30% for complex proteoforms. A HIquant server is implemented at:
      https://web.northeastern.edu/slavov/2014_HIquant/.

PMID- 30282778
TI  - Chris and Xand van Tulleken: Sibling revelry.

PMID- 30282779
TI  - Student-led service evaluation of doctor introductions to patients.

PMID- 30282780
TI  - Warfarin-induced unilateral facial swelling and skin rash.

PMID- 30282777
TI  - Activated CaMKIIalpha Binds to the mGlu5 Metabotropic Glutamate Receptor and
      Modulates Calcium Mobilization.
AB  - Ca2+/calmodulin-dependent protein kinase II (CaMKII) and metabotropic glutamate
      receptor 5 (mGlu5) are critical signaling molecules in synaptic plasticity and
      learning/memory. Here, we demonstrate that mGlu5 is present in CaMKIIalpha
      complexes isolated from mouse forebrain. Further in vitro characterization showed
      that the membrane-proximal region of the C-terminal domain (CTD) of mGlu5a
      directly interacts with purified Thr286-autophosphorylated (activated)
      CaMKIIalpha However, the binding of CaMKIIalpha to this CTD fragment is reduced
      by the addition of excess Ca2+/calmodulin or by additional CaMKIIalpha
      autophosphorylation at non-Thr286 sites. Furthermore, in vitro binding of
      CaMKIIalpha is dependent on a tribasic residue motif Lys-Arg-Arg (KRR) at
      residues 866-868 of the mGlu5a-CTD, and mutation of this motif decreases the
      coimmunoprecipitation of CaMKIIalpha with full-length mGlu5a expressed in
      heterologous cells by about 50%. The KRR motif is required for two novel
      functional effects of coexpressing constitutively active CaMKIIalpha with mGlu5a
      in heterologous cells. First, cell-surface biotinylation studies showed that
      CaMKIIalpha increases the surface expression of mGlu5a Second, using Ca2+
      fluorimetry and single-cell Ca2+ imaging, we found that CaMKIIalpha reduces the
      initial peak of mGlu5a-mediated Ca2+ mobilization by about 25% while doubling the
      relative duration of the Ca2+ signal. These findings provide new insights into
      the physical and functional coupling of these key regulators of postsynaptic
      signaling.

PMID- 30282781
TI  - Microscopic polyangiitis after streptococcal pharyngitis in a young woman.

PMID- 30282782
TI  - Variation in Use by NICU Types in the United States.
AB  - : : media-1vid110.1542/5828370139001PEDS-VA_2018-0457Video Abstract BACKGROUND:
      Increased admissions of higher birth weight and less acutely ill infants to NICUs
      suggests that intensive care may be used inappropriately in these populations. We
      describe variation in use of NICU services by gestational age and NICU type.
      METHODS: Using the Vermont Oxford Network database of all NICU admissions, we
      assessed variation within predefined gestational age categories in the following
      proportions: admissions, initial NICU hospitalization days, high-acuity cases
      >=34 weeks' gestation, and short-stay cases >=34 weeks' gestation. High acuity
      was defined as follows: death, intubated assisted ventilation for >=4 hours,
      early bacterial sepsis, major surgery requiring anesthesia, acute transport to
      another center, hypoxic-ischemic encephalopathy or a 5-minute Apgar score <=3, or
      therapeutic hypothermia. Short stay was defined as an inborn infant staying 1 to
      3 days with discharge from the hospital. RESULTS: From 2014 to 2016, 486 741
      infants were hospitalized 9 657 508 days at 381 NICUs in the United States. The
      median proportions of admissions, initial hospitalized days, high-acuity cases,
      and short stays varied significantly by NICU types in almost all gestational age
      categories. Fifteen percent of the infants >=34 weeks were high acuity, and 10%
      had short stays. CONCLUSIONS: There is substantial variation in use among NICUs.
      A campaign to focus neonatal care teams on using the NICU wisely that addresses
      the appropriate use of intensive care for newborn infants and accounts for local
      context and the needs of families is needed.

PMID- 30282783
TI  - An Electronic Referral and Social Work Protocol to Improve Access to Mental
      Health Services.
AB  - BACKGROUND AND OBJECTIVES: The prevalence of mental health problems among
      adolescents in the United States is a major public health concern. However, the
      uptake of mental health treatment is low. Integrating behavioral health into
      primary care is 1 research-informed strategy to increase engagement in treatment.
      Facilitators of and barriers to implementation of integrated behavioral health in
      a pediatric primary care setting are not well delineated. METHODS: We examined
      the effectiveness of 2 mental health quality improvement strategies: an
      electronic referral and a social work follow-up protocol. We analyzed the
      following measures: uptake rate of first mental health appointments, overall use
      of mental health appointments, and first and overall mental health appointment
      show rate. RESULTS: Overall use rate improved after implementation of electronic
      referral, with 13 consecutive points above the median. First appointment show
      rates improved with a special cause run occurring after adding social work
      students to the mental health quality improvement team. First appointment show
      rate improved from a monthly average of 51% (November 2014 to March 2016) to 78%
      (April 2016 to December 2016). Use rate improved initially with increased efforts
      in assisting patients with scheduling; show rate improved more slowly after an
      emphasis on scheduling patients exhibiting treatment readiness. CONCLUSIONS:
      Findings suggest that a number of facilitators can increase the effective use of
      mental health services in an integrated adolescent clinical setting. These
      include an electronic referral through a shared electronic health record,
      multidisciplinary collaboration, and care management by social workers equipped
      with a variety of clinical and care coordination skills.

PMID- 30282784
TI  - Direct-from-Stool Testing for Shiga Toxins by an Immunochromatographic Assay Is
      Insensitive for Detection of Shigatoxigenic Escherichia coli.

PMID- 30282785
TI  - Distribution of Kingella kingae Capsular Serotypes in France Assessed by a
      Multiplex PCR Assay on Osteoarticular Samples.

PMID- 30282786
TI  - Medical Parasitology Taxonomy Update, 2016-2017.
AB  - Parasite taxonomy continues to change as molecular and morphologic studies
      enhance our understanding of parasite relatedness. This minireview builds on the
      information provided in the last taxonomy update in this journal to summarize new
      and revised clinically-relevant human parasite taxonomic changes that have
      occurred in 2016-2017.

PMID- 30282787
TI  - Identification and Characterization of Orientia chuto in Trombiculid Chigger
      Mites Collected from Wild Rodents in Kenya.
AB  - We present data that concurs with the reported geographical expansion of scrub
      typhus outside the "Tsutsugamushi Triangle" and addition of Orientia chuto as a
      second species in the Orientia genus. Wild rodents were caught in Marigat,
      Baringo County, Kenya, and ectoparasites, including chiggers, were recovered.
      Rodent and chigger species were identified by taxonomic features. DNA was
      extracted from the chiggers and used to amplify and/or sequence the 47-kDa high
      temperature transmembrane protein (TSA47), the 56-kDa type-specific antigen
      (TSA56), and the 16S rRNA (rrs) Orientia genes. The main rodent hosts identified
      were Acomys wilsoni, Crocidura sp., and Mastomys natalensis, which accounted for
      59.2% of the total collection. Of these, A. wilsoni and M. natalensis harbored
      most of the chiggers that belonged to the Neotrombicula and Microtrombicula
      genera. A pool of chiggers from one of M. natalensis was positive for Orientia by
      TSA47 PCR, but Orientia did not amplify with the TSA56 primers. On sequencing the
      850 bp of the TSA47 gene, the closest phylogenetic relative was O. chuto, with
      97.65% sequence homology compared to 84.63 to 84.76% for O. tsutsugamushi 16S
      rRNA deep sequencing also revealed O. chuto as the closest phylogenetic relative,
      with 99.75% sequence homology. These results and the existing immunological and
      molecular reports are strongly suggestive of the existence of Orientia species in
      Kenya.

PMID- 30282789
TI  - Blood Culture Results Reporting: How Fast Is Your Laboratory and Is Faster
      Better?
AB  - Blood cultures are one of the most common and most important tests performed in
      clinical microbiology laboratories. Variables and technology that improve and
      speed the recovery of blood stream pathogens have been published in the Journal
      of Clinical Microbiology since its inception in 1975. Despite the importance of
      blood cultures, little research has focused on the turnaround time of blood
      culture reports. In this issue of the Journal of Clinical Microbiology, Y. P.
      Tabak et al. (J Clin Microbiol 56:e00500-18, 2018,
      https://doi.org/10.1128/JCM.00500-18) report the results of an investigation of
      Gram stain, organism identification, and susceptibility report turnaround times
      for 165,593 blood cultures from 13 laboratories. These data provide a starting
      point for clinical laboratories to establish targets for blood culture result
      reporting.

PMID- 30282788
TI  - Does Size Matter? Comparison of Extraction Yields for Different-Sized DNA
      Fragments by Seven Different Routine and Four New Circulating Cell-Free
      Extraction Methods.
AB  - An element essential for PCR detection of microbial agents in many sample types
      is the extraction step, designed to purify nucleic acids. Despite the importance
      of this step, yields have not been extensively compared across methods to
      determine whether the method used contributes to quantitative differences and the
      lack of commutability seen with existing clinical methods. This may in part
      explain why plasma and blood viral load assays have proven difficult to
      standardize. Also, studies have identified small DNA fragments of <200 bp in
      plasma (cell-free DNA [cfDNA]), which may include significant quantities of viral
      DNA. Our study evaluated extraction yields for 11 commercially available
      extraction methods, including 4 new methods designed to isolate cfDNA. Solutions
      of DNA fragments with sizes ranging from 50 to 1,500 bp were extracted, and then
      the eluates were tested by droplet digital PCR to determine the DNA fragment
      yield for each method. The results demonstrated a wide range of extraction yields
      across the variety of methods/instruments used, with the 50- and 100-bp fragment
      sizes showing especially inconsistent quantitative results and poor yields of
      less than 20%. Slightly higher, more consistent yields were seen with 2 of the 4
      circulating cell-free extraction kits. These results demonstrate a significant
      need for further evaluation of nucleic acid yields across the variety of
      extraction platforms and highlight the poor extraction yields of small DNA
      fragments by existing methods. Further work is necessary to determine the impact
      of this inconsistency across instruments and the relevance of the low yields for
      smaller DNA fragments in clinical virology testing.

PMID- 30282790
TI  - Utility of a Rapid Lateral Flow Assay To Resolve Erroneous Identification of
      Burkholderia pseudomallei as Burkholderia thailandensis by Matrix-Assisted Laser
      Desorption Ionization-Time of Flight (MALDI-TOF) Mass Spectrometry.

PMID- 30282791
TI  - Two-Site Evaluation of the Colistin Broth Disk Elution Test to Determine Colistin
      In Vitro Activity Against Gram-Negative Bacilli.
AB  - Background: Limited methods for colistin minimum inhibitory concentration (MIC)
      determination are available to clinical microbiology laboratories. The purpose of
      this study was to evaluate the accuracy of the colistin broth disk elution (CBDE)
      test as compared to broth microdilution (BMD) for identifying colistin
      MICs.Methods: CBDE was compared to colistin BMD using a collection of Gram
      negative bacilli tested at two U.S. microbiology laboratories. Isolates tested
      included 121 retrospective clinical isolates, 45 prospective clinical isolates,
      and 6 mcr-1 positive E. coli CBDE was performed with four, 10 ml cation-adjusted
      Mueller Hinton broth tubes per isolate, to which 0, 1, 2, and 4 colistin 10 ug
      disks were added, generating a final concentration of 0 (growth control), 1, 2
      and 4 ug/mL in the tubes. MICs were evaluated visually and interpreted using CLSI
      breakpoints. Site 2 also compared CBDE to reference broth macrodilution (BMAD, n=
      110 isolates).Results: Overall, CBDE yielded a categorical agreement (CA) and
      essential agreement (EA) of 98% and 99%, respectively, compared to colistin BMD.
      Very major errors occurred for mcr-1 producing strains with MICs that fluctuated
      on repeat testing from 2 to 4 ug/mL. All other isolates were in CA with BMD. CBDE
      versus BMAD had an EA of 100% and CA of 100%.Conclusions: Compared to currently
      used techniques, CBDE is an easy and practical method to perform colistin
      testing. Some mcr-1 isolates yielded MICs of 2 ug/mL by CBDE and 4 ug/mL by BMD.
      As such, isolates with colistin MICs of 2 ug/mL by CBDE should be confirmed by
      reference BMD and those with MIC >= 2 ug/mL should be evaluated for mcr genes.

PMID- 30282792
TI  - 'How can patient and carers' experiences shape services?' The Royal Society of
      Medicine palliative care competition.
AB  - Quality improvement can be difficult to assess and monitor in palliative care due
      to the nature of the specialty. This essay investigates ways in which this is
      currently carried out by assessing the benefits of patient-centred outcome
      measures. Potential technological improvements which could be implemented in the
      future are also discussed. This is an award-winning essay which subsequently
      complemented a separate project which analysed the use of the Integrated
      Palliative Care Outcome Scale in an inpatient palliative care unit.

PMID- 30282793
TI  - Role of clinical psychology in UK hospices.
AB  - OBJECTIVE: The National Institute of Clinical Excellence (NICE) (2004) guidance
      recommends a tiered approach to psychological care within cancer care. This
      includes the provision of Clinical Psychologists to support other professionals
      to deliver high-quality psychological care at levels 1 and 2 and to provide
      direct input to patients experiencing high levels of distress at level 4.
      However, little is known about the role of Clinical Psychology within UK Hospices
      currently. A survey of Clinical Psychologists working in this area was undertaken
      to address this gap in knowledge. METHODS: We conducted an anonymous online
      survey of Clinical Psychologists working in Hospice organisations across the UK.
      Recruitment was completed via professional networking groups, social media and by
      contacting UK Hospice organisations. The survey included quantitative and
      qualitative items about professionals' experience, how their input is organised,
      their roles and activities and their views on the valuable and challenging
      aspects of working in this setting. RESULTS: Eighteen Clinical Psychologists
      responded and there was considerable variance in how their roles were organised.
      The tasks undertaken by most respondents were direct work with and consultation
      for hospice patients, and teaching and training staff. However, the findings
      demonstrated that Clinical Psychologists can undertake a wide range of tasks and
      draw on a range of therapeutic approaches including Cognitive Behavioural
      Therapy, Acceptance and Commitment Therapy and Compassion Focused Therapy, in
      their hospice work. CONCLUSION: Our results provide an overview of the role of
      Clinical Psychology in UK Hospices and demonstrate the contribution that
      Psychologists can make to this field.

PMID- 30282795
TI  - Conservative conference: Hancock pledges extra cash for social care and expansion
      of genomic medicine.

PMID- 30282796
TI  - GP at Hand adverts were misleading to patients, watchdog rules.

PMID- 30282794
TI  - The Number of Meiotic Double-Strand Breaks Influences Crossover Distribution in
      Arabidopsis.
AB  - Meiotic recombination generates genetic diversity and ensures proper chromosome
      segregation. Recombination is initiated by the programmed formation of double
      strand breaks (DSBs) in chromosomal DNA by DNA Topoisomerase VI-A Subunit
      (SPO11), a topoisomerase-like enzyme. Repair of some DSBs leads to the formation
      of crossovers (COs). In most organisms, including plants, the number of DSBs
      greatly exceeds the number of COs and which DSBs become CO sites is tightly
      controlled. The CO landscape is affected by DNA sequence and epigenome features
      of chromosomes as well as by global mechanisms controlling recombination
      dynamics. The latter are poorly understood and their effects on CO distribution
      are not well elucidated. To study how recombination dynamics affects CO
      distribution, we engineered Arabidopsis thaliana plants to carry hypomorphic
      alleles of SPO11-1 Two independent transgenic lines showed ~30% and 40%
      reductions in DSB numbers, which were commensurate with the dosage of the SPO11-1
      transcript. The reduction in DSB number resulted in proportional, although
      smaller, reductions of the number of COs. Most interestingly, CO distribution
      along the chromosomes was dramatically altered, with substantially fewer COs
      forming in pericentromeric chromosome regions. These results indicate that SPO11
      activity, and the resulting DSB numbers are major factors shaping the CO
      landscape.

PMID- 30282797
TI  - FLT3 pathway is a potential therapeutic target for PRC2-mutated T-cell acute
      lymphoblastic leukemia.

PMID- 30282798
TI  - Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma.
AB  - <pIt is important to have an effective therapy for multiple myeloma (MM) patients
      at first relapse, particularly if an autologous stem cell transplant (ASCT) is
      considered at this stage. This multicenter, phase II trial evaluated the efficacy
      and safety of weekly oral pomalidomide-cyclophosphamide-dexamethasone (PCD) in MM
      patients in first relapse after treatment with lenalidomide-bortezomib
      dexamethasone (RVD). All patients had received RVD as induction and consolidation
      therapy, plus lenalidomide maintenance for 1 year (Arm A). Half had also received
      an ASCT after induction (Arm B). At MM relapse, all patients received four oral
      cycles of pomalidomide 4 mg (Days 1-21), cyclophosphamide 300 mg (Days 1, 8, 15
      and 22), and dexamethasone 40 mg (Days 1-4 and Days 15-18 of a 28-day cycle)
      (PCD). Responding patients in Arm A underwent ASCT and received two additional
      cycles of PCD, while those in Arm B received five cycles of PCD. All patients
      received pomalidomide-dexamethasone maintenance until disease progression.
      Primary endpoint was partial remission or better after the initial four cycles of
      PCD. Responses were obtained in 82/97 (85%) patients evaluated: complete
      remission (n=1; 1%); very good partial remission (n=32; 33%); partial remission
      (PR) (n=49; 51%). Three patients (3%) had stable disease and six (6%) had disease
      progression (6 response failures). Forty-five of the 48 patients (94%) in Arm A
      underwent planned ASCT. PCD was effective therapy after first relapse with RVD.
      After four cycles, the rate of PR or better was 85%, and 94% of planned ASCTs
      were performed. Toxicity was mostly hematologic and manageable. This trial was
      registered at www.clinicaltrials.gov, NCT02244125.

PMID- 30282799
TI  - IG-MYC + neoplasms with precursor B-cell phenotype are molecularly distinct from
      Burkitt lymphomas.
AB  - The WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue notes
      instances of Burkitt lymphoma/leukemia (BL) with IG-MYC rearrangement displaying
      a B-cell precursor immunophenotype (termed herein "preBLL"). To characterize the
      molecular pathogenesis of preBLL, we investigated 13 preBLL cases (including 1
      cell line), of which 12 were analyzable using genome, exome, and targeted
      sequencing, imbalance mapping, and DNA methylation profiling. In 5 patients with
      reads across the IG-MYC breakpoint junctions, we found evidence that the
      translocation derived from an aberrant VDJ recombination, as is typical for IG
      translocations arising in B-cell precursors. Genomic changes like biallelic IGH
      translocations or VDJ rearrangements combined with translocation into the VDJ
      region on the second allele, potentially preventing expression of a productive
      immunoglobulin, were detected in 6 of 13 cases. We did not detect mutations in
      genes frequently altered in BL, but instead found activating NRAS and/or KRAS
      mutations in 7 of 12 preBLLs. Gains on 1q, recurrent in BL and preB lymphoblastic
      leukemia/lymphoma (pB-ALL/LBL), were detected in 7 of 12 preBLLs. DNA methylation
      profiling showed preBLL to cluster with precursor B cells and pB-ALL/LBL, but
      apart from BL. We conclude that preBLL genetically and epigenetically resembles
      pB-ALL/LBL rather than BL. Therefore, we propose that preBLL be considered as a
      pB-ALL/LBL with recurrent genetic abnormalities.

PMID- 30282800
TI  - Platelet-derived TLT-1 is a prognostic indicator in ALI/ARDS and prevents tissue
      damage in the lungs in a mouse model.
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) affect
      >200 000 individuals yearly with a 40% mortality rate. Although platelets are
      implicated in the progression of ALI/ARDS, their exact role remains undefined.
      Triggering receptor expressed in myeloid cells (TREM)-like transcript 1 (TLT-1)
      is found on platelets, binds fibrinogen, and mediates clot formation. We
      hypothesized that platelets use TLT-1 to manage the progression of ALI/ARDS. Here
      we retrospectively measure plasma levels of soluble TLT-1 (sTLT-1) from the ARDS
      Network clinical trial and show that patients whose sTLT-1 levels were >1200
      pg/mL had nearly twice the mortality risk as those with <1200 pg/mL (P < .001).
      After correcting for confounding factors such as creatinine levels, Acute
      Physiology And Chronic Health Evaluation III scores, age, platelet counts, and
      ventilation volume, sTLT-1 remains significant, suggesting that sTLT-1 is an
      independent prognostic factor (P < .0001). These data point to a role for TLT-1
      during the progression of ALI/ARDS. We use a murine lipopolysaccharide-induced
      ALI model and demonstrate increased alveolar bleeding, aberrant neutrophil
      transmigration and accumulation associated with decreased fibrinogen deposition,
      and increased pulmonary tissue damage in the absence of TLT-1. The loss of TLT-1
      resulted in an increased proportion of platelet-neutrophil conjugates (43.73 +/-
      24.75% vs 8.92 +/- 2.4% in wild-type mice), which correlated with increased
      neutrophil death. Infusion of sTLT-1 restores normal fibrinogen deposition and
      reduces pulmonary hemorrhage by 40% (P <= .001) and tissue damage by 25% (P <=
      .001) in vivo. Our findings suggest that TLT-1 uses fibrinogen to govern the
      transition between inflammation and hemostasis and facilitate controlled
      leukocyte transmigration during the progression of ARDS.

PMID- 30282801
TI  - Sirtuin 7-mediated deacetylation of WD repeat domain 77 (WDR77) suppresses cancer
      cell growth by reducing WDR77/PRMT5 transmethylase complex activity.
AB  - The histone transmethylase complex comprising WD repeat domain 77 (WDR77) and
      protein arginine methyltransferase 5 (PRMT5) catalyzes dimethylation of H4R3
      (H4R3me2) and drives cancer cell proliferation and migration, but its regulation
      is not fully understood. Here, we report that sirtuin 7 (SIRT7) directly
      deacetylates WDR77 and that this deacetylation interferes with the WDR77-PRMT5
      interaction and suppresses proliferation of human colon cancer HCT116 cells.
      Using co-expression in HEK293T cells and co-immunoprecipitation assays, we
      observed that SIRT7 deacetylates WDR77 at Lys-3 and Lys-243, which reduced of
      WDR77's interaction with PRMT5. More importantly, this reduction suppressed the
      transmethylase activity of the WDR77/PRMT5 complex, resulting in a reduction of
      the H4R3me2 modification. Rescue of the WDR77-KO HCT116 cells with a WDR77-2KR
      (K3R and K243R) variant yielded cell migration and proliferation rates that were
      significantly lower than those of WDR77-KO HCT116 cells rescued with WT WDR77. In
      summary, SIRT7 is a major deacetylase for WDR77, and SIRT7-mediated deacetylation
      of WDR77 at Lys-3 and Lys-243 weakens the WDR77-PRMT5 interaction and activity
      and thereby suppresses growth of cancer cells.

PMID- 30282802
TI  - OTUB1 non-catalytically stabilizes the E2 ubiquitin-conjugating enzyme UBE2E1 by
      preventing its autoubiquitination.
AB  - OTUB1 is a deubiquitinating enzyme that cleaves Lys-48-linked polyubiquitin
      chains and also regulates ubiquitin signaling through a unique, noncatalytic
      mechanism. OTUB1 binds to a subset of E2 ubiquitin-conjugating enzymes and
      inhibits their activity by trapping the E2~ubiquitin thioester and preventing
      ubiquitin transfer. The same set of E2s stimulate the deubiquitinating activity
      of OTUB1 when the E2 is not charged with ubiquitin. Previous studies have shown
      that, in cells, OTUB1 binds to E2-conjugating enzymes of the UBE2D (UBCH5) and
      UBE2E families, as well as to UBE2N (UBC13). Cellular roles have been identified
      for the interaction of OTUB1 with UBE2N and members of the UBE2D family, but not
      for interactions with UBE2E E2 enzymes. We report here a novel role for OTUB1-E2
      interactions in modulating E2 protein ubiquitination. We observe that Otub1 -/-
      knockout mice exhibit late-stage embryonic lethality. We find that OTUB1
      depletion dramatically destabilizes the E2-conjugating enzyme UBE2E1 (UBCH6) in
      both mouse and human OTUB1 knockout cell lines. Of note, this effect is
      independent of the catalytic activity of OTUB1, but depends on its ability to
      bind to UBE2E1. We show that OTUB1 suppresses UBE2E1 autoubiquitination in vitro
      and in cells, thereby preventing UBE2E1 from being targeted to the proteasome for
      degradation. Taken together, we provide evidence that OTUB1 rescues UBE2E1 from
      degradation in vivo.

PMID- 30282803
TI  - A helical LC3-interacting region mediates the interaction between the retroviral
      restriction factor Trim5alpha and mammalian autophagy-related ATG8 proteins.
AB  - The retroviral restriction factor tripartite motif-containing 5alpha (Trim5alpha)
      acts during the early postentry stages of the retroviral life cycle to block
      infection by a broad range of retroviruses, disrupting reverse transcription and
      integration. The mechanism of this restriction is poorly understood, but it has
      recently been suggested to involve recruitment of components of the autophagy
      machinery, including members of the mammalian autophagy-related 8 (ATG8) family
      involved in targeting proteins to the autophagosome. To better understand the
      molecular details of this interaction, here we utilized analytical
      ultracentrifugation to characterize the binding of six ATG8 isoforms and
      determined the crystal structure of the Trim5alpha Bbox coiled-coil region in
      complex with one member of the mammalian ATG8 proteins, autophagy-related protein
      LC3 B (LC3B). We found that Trim5alpha binds all mammalian ATG8s and that, unlike
      the typical LC3-interacting region (LIR) that binds to mammalian ATG8s through a
      beta-strand motif comprising approximately six residues, LC3B binds to Trim5alpha
      via the alpha-helical coiled-coil region. The orientation of the structure
      demonstrated that LC3B could be accommodated within a Trim5alpha assembly that
      can bind the retroviral capsid. However, mutation of the binding interface does
      not affect retroviral restriction. Comparison of the typical linear beta-strand
      LIR with our atypical helical LIR reveals a conservation of the presentation of
      residues that are required for the interaction with LC3B. This observation
      expands the range of LC3B-binding proteins to include helical binding motifs and
      demonstrates a link between Trim5alpha and components of the autophagosome.

PMID- 30282804
TI  - Structural basis of inactivation of Ras and Rap1 small GTPases by Ras/Rap1
      specific endopeptidase from the sepsis-causing pathogen Vibrio vulnificus.
AB  - Multifunctional autoprocessing repeats-in-toxin (MARTX) toxins are secreted by
      Gram-negative bacteria and function as primary virulence-promoting macromolecules
      that deliver multiple cytopathic and cytotoxic effector domains into the host
      cytoplasm. Among these effectors, Ras/Rap1-specific endopeptidase (RRSP)
      catalyzes the sequence-specific cleavage of the Switch I region of the cellular
      substrates Ras and Rap1 that are crucial for host innate immune defenses during
      infection. To dissect the molecular basis underpinning RRSP-mediated substrate
      inactivation, we determined the crystal structure of an RRSP from the sepsis
      causing bacterial pathogen Vibrio vulnificus (VvRRSP). Structural and biochemical
      analyses revealed that VvRRSP is a metal-independent TIKI family endopeptidase
      composed of an N-terminal membrane-localization and substrate-recruitment domain
      (N lobe) connected via an inter-lobe linker to the C-terminal active site
      coordinating core beta-sheet-containing domain (C lobe). Structure-based
      mutagenesis identified the 2His/2Glu catalytic residues in the core catalytic
      domain that are shared with other TIKI family enzymes and that are essential for
      Ras processing. In vitro KRas cleavage assays disclosed that deleting the N lobe
      in VvRRSP causes complete loss of enzymatic activity. Endogenous Ras cleavage
      assays combined with confocal microscopy analysis of HEK293T cells indicated that
      the N lobe functions both in membrane localization via the first alpha-helix and
      in substrate assimilation by altering the functional conformation of the C lobe
      to facilitate recruitment of cellular substrates. Collectively, these results
      indicate that RRSP is a critical virulence factor that robustly inactivates Ras
      and Rap1 and augments the pathogenicity of invading bacteria via the combined
      effects of its N and C lobes.

PMID- 30282805
TI  - Transcriptional regulation of the matrix protein Shematrin-2 during shell
      formation in pearl oyster.
AB  - The molluscan shell is a fascinating biomineral consisting of a highly organized
      calcium carbonate composite. Biomineralization is elaborately controlled and
      involves several macromolecules, especially matrix proteins, but little is known
      about the regulatory mechanisms. The matrix protein Shematrin-2, expression of
      which peaks in the mantle tissues and in the shell components of the pearl oyster
      Pinctada fucata, has been suggested to be a key participant in biomineralization.
      Here, we expressed and purified Shematrin-2 from P. fucata and explored its
      function and transcriptional regulation. An in vitro functional assay revealed
      that Shematrin-2 binds the calcite, aragonite, and chitin components of the
      shell, decreases the rate of calcium carbonate deposition, and changes the
      morphology of the deposited crystal in the calcite crystallization system.
      Furthermore, we cloned the Shematrin-2 gene promoter, and analysis of its
      sequence revealed putative binding sites for the transcription factors CCAAT
      enhancer-binding proteins (Pf-C/EBPs) and nuclear factor-Y (NF-Y). Using
      transient co-transfection and reporter gene assays, we found that cloned and
      recombinantly expressed Pf-C/EBP-A and Pf-C/EBP-B greatly and dose-dependently up
      regulate the promoter activity of the Shematrin-2 gene. Importantly, Pf-C/EBP-A
      and Pf-C/EBP-B knockdowns decreased Shematrin-2 gene expression and induced
      changes in the inner-surface structures in prismatic layers that were similar to
      those of antibody-based Shematrin-2 inhibition. Altogether, our data reveal that
      the transcription factors Pf-C/EBP-A and Pf-C/EBP-B up-regulate the expression of
      the matrix protein Shematrin-2 during shell formation in P. fucata, improving our
      understanding of the transcriptional regulation of molluscan shell development at
      the molecular level.

PMID- 30282807
TI  - A complete bioconversion cascade for dehalogenation and denitration by bacterial
      flavin-dependent enzymes.
AB  - Halogenated phenol and nitrophenols are toxic compounds that are widely
      accumulated in the environment. Enzymes in the had operon from the bacterium
      Ralstonia pickettii DTP0602 have the potential for application as biocatalysts in
      the degradation of many of these toxic chemicals. HadA monooxygenase previously
      was identified as a two-component reduced FAD (FADH-)-utilizing monooxygenase
      with dual activities of dehalogenation and denitration. However, the partner
      enzymes of HadA, that is, the flavin reductase and quinone reductase that provide
      the FADH- for HadA and reduce quinone to hydroquinone, remain to be identified.
      In this report, we overexpressed and purified the flavin reductases, HadB and
      HadX, to investigate their functional and catalytic properties. Our results
      indicated that HadB is an FMN-dependent quinone reductase that converts the
      quinone products from HadA to hydroquinone compounds that are more stable and can
      be assimilated by downstream enzymes in the pathway. Transient kinetics indicated
      that HadB prefers NADH and menadione as the electron donor and acceptor,
      respectively. We found that HadX is an FAD-bound flavin reductase, which can
      generate FADH- for HadA to catalyze dehalogenation or denitration reactions.
      Thermodynamic and transient kinetic experiments revealed that HadX prefers to
      bind FAD over FADH- and that HadX can transfer FADH- from HadX to HadA via free
      diffusion. Moreover, HadX rapidly catalyzed NADH-mediated reduction of flavin and
      provided the FADH- for a monooxygenase of a different system. Combination of all
      three flavin-dependent enzymes, i.e. HadA/HadB/HadX, reconstituted an effective
      dehalogenation and denitration cascade, which may be useful for future
      bioremediation applications.

PMID- 30282806
TI  - Mechanistic insights into the interaction of the MOG1 protein with the cardiac
      sodium channel Nav1.5 clarify the molecular basis of Brugada syndrome.
AB  - Nav1.5 is the alpha-subunit of the cardiac sodium channel complex. Abnormal
      expression of Nav1.5 on the cell surface because of mutations that disrupt Nav1.5
      trafficking causes Brugada syndrome (BrS), sick sinus syndrome (SSS), cardiac
      conduction disease, dilated cardiomyopathy, and sudden infant death syndrome. We
      and others previously reported that Ran-binding protein MOG1 (MOG1), a small
      protein that interacts with Nav1.5, promotes Nav1.5 intracellular trafficking to
      plasma membranes and that a substitution in MOG1, E83D, causes BrS. However, the
      molecular basis for the MOG1/Nav1.5 interaction and how the E83D substitution
      causes BrS remains unknown. Here, we assessed the effects of defined MOG1
      deletions and alanine-scanning substitutions on MOG1's interaction with Nav1.5.
      Large deletion analysis mapped the MOG1 domain required for the interaction with
      Nav1.5 to the region spanning amino acids 146-174, and a refined deletion
      analysis further narrowed this domain to amino acids 146-155. Site-directed
      mutagenesis further revealed that Asp-148, Arg-150, and Ser-151 cluster in a
      peptide loop essential for binding to Nav1.5. GST pulldown and
      electrophysiological analyses disclosed that the substitutions E83D, D148Q,
      R150Q, and S151Q disrupt MOG1's interaction with Nav1.5 and significantly reduce
      its trafficking to the cell surface. Examination of MOG1's 3D structure revealed
      that Glu-83 and the loop containing Asp-148, Arg-150, and Ser-151 are spatially
      proximal, suggesting that these residues form a critical binding site for Nav1.5.
      In conclusion, our findings identify the structural elements in MOG1 that are
      crucial for its interaction with Nav1.5 and improve our understanding of how the
      E83D substitution causes BrS.

PMID- 30282809
TI  - Mathematical modeling reveals spontaneous emergence of self-replication in
      chemical reaction systems.
AB  - Explaining the origin of life requires us to elucidate how self-replication
      arises. To be specific, how can a self-replicating entity develop spontaneously
      from a chemical reaction system in which no reaction is self-replicating?
      Previously proposed mathematical models either supply an explicit framework for a
      minimal living system or consider only catalyzed reactions, and thus fail to
      provide a comprehensive theory. Here, we set up a general mathematical model for
      chemical reaction systems that properly accounts for energetics, kinetics, and
      the conservation law. We found that (1) some systems are collectively-catalytic,
      a mode whereby reactants are transformed into end products with the assistance of
      intermediates (as in the citric acid cycle), whereas some others are self
      replicating, that is, different parts replicate each other and the system self
      replicates as a whole (as in the formose reaction, in which sugar is replicated
      from formaldehyde); (2) side reactions do not always inhibit such systems; (3)
      randomly chosen chemical universes (namely, random artificial chemistries) often
      contain one or more such systems; (4) it is possible to construct a self
      replicating system in which the entropy of some parts spontaneously decreases, in
      a manner similar to that discussed by Schrodinger; and (5) complex self
      replicating molecules can emerge spontaneously and relatively easily from simple
      chemical reaction systems through a sequence of transitions. Together, these
      results start to explain the origins of prebiotic evolution.

PMID- 30282808
TI  - Endo-fucoidan hydrolases from glycoside hydrolase family 107 (GH107) display
      structural and mechanistic similarities to alpha-l-fucosidases from GH29.
AB  - Fucoidans are chemically complex and highly heterogeneous sulfated marine fucans
      from brown macro algae. Possessing a variety of physicochemical and biological
      activities, fucoidans are used as gelling and thickening agents in the food
      industry and have anticoagulant, antiviral, antitumor, antibacterial, and immune
      activities. Although fucoidan-depolymerizing enzymes have been identified, the
      molecular basis of their activity on these chemically complex polysaccharides
      remains largely uninvestigated. In this study, we focused on three glycoside
      hydrolase family 107 (GH107) enzymes: MfFcnA and two newly identified members,
      P5AFcnA and P19DFcnA, from a bacterial species of the genus Psychromonas Using
      carbohydrate-PAGE, we show that P5AFcnA and P19DFcnA are active on fucoidans that
      differ from those depolymerized by MfFcnA, revealing differential substrate
      specificity within the GH107 family. Using a combination of X-ray crystallography
      and NMR analyses, we further show that GH107 family enzymes share features of
      their structures and catalytic mechanisms with GH29 alpha-l-fucosidases. However,
      we found that GH107 enzymes have the distinction of utilizing a histidine side
      chain as the proposed acid/base catalyst in its retaining mechanism. Further
      interpretation of the structural data indicated that the active-site
      architectures within this family are highly variable, likely reflecting the
      specificity of GH107 enzymes for different fucoidan substructures. Together,
      these findings begin to illuminate the molecular details underpinning the
      biological processing of fucoidans.

PMID- 30282810
TI  - Aneuploidy in intestinal stem cells promotes gut dysplasia in Drosophila.
AB  - Aneuploidy is associated with different human diseases including cancer. However,
      different cell types appear to respond differently to aneuploidy, either by
      promoting tumorigenesis or causing cell death. We set out to study the behavior
      of adult Drosophila melanogaster intestinal stem cells (ISCs) after induction of
      chromosome missegregation either by abrogation of the spindle assembly checkpoint
      or through kinetochore disruption or centrosome amplification. These conditions
      induce moderate levels of aneuploidy in ISCs, and we find no evidence of
      apoptosis. Instead, we observe a significant accumulation of ISCs associated with
      increased stem cell proliferation and an excess of enteroendocrine cells.
      Moreover, aneuploidy causes up-regulation of the JNK pathway throughout the
      posterior midgut, and specific inhibition of JNK signaling in ISCs is sufficient
      to prevent dysplasia. Our findings highlight the importance of understanding the
      behavior of different stem cell populations to aneuploidy and how these can act
      as reservoirs for genomic alterations that can lead to tissue pathologies.

PMID- 30282813
TI  - Immune effector functions of human IgG2 antibodies against EGFR.
AB  - Three FDA approved epidermal growth factor receptor (EGFR) antibodies (Cetuximab,
      Panitumumab, Necitumumab) are clinically available to treat patients with
      different types of cancer. Interestingly, Panitumumab is of human IgG2 isotype,
      which is often considered to have limited immune effector functions.
      Unexpectedly, our studies unraveled that human IgG2 antibodies against EGFR
      mediated effective CDC when combined with another non cross-blocking EGFR
      antibody. This second antibody could be of human IgG1 or IgG2 isotype.
      Furthermore, EGFR antibodies of human IgG2 isotype were highly potent in
      recruiting myeloid effector cells such as M1 macrophages and PMN for tumor cell
      killing by ADCC. Tumor cell killing by PMN was more effective with IgG2 than with
      IgG1 antibodies if tumor cells expressed lower levels of EGFR. Additionally,
      lower expression levels of the "don't eat me" molecule CD47 on tumor cells
      enabeled ADCC also by M2 macrophages, and improved PMN and macrophage mediated
      ADCC. A TCGA enquiry revealed broadly varying CD47 expression levels across
      different solid tumor types. Together, these results demonstrate that human IgG2
      antibodies against EGFR can promote significant Fc mediated effector functions,
      which may contribute to their clinical efficacy. The future challenge will be to
      identify clinical situations in which myeloid effector cells can optimally
      contribute to antibody efficacy.

PMID- 30282812
TI  - mTORC1/2 and Protein Translation Regulate Levels of CHK1 and the Sensitivity to
      CHK1 Inhibitors in Ewing Sarcoma Cells.
AB  - The treatment of Ewing sarcoma has changed very little in the past two decades
      and novel treatment approaches are needed. We recently identified that Ewing
      sarcoma cells are uniquely vulnerable to inhibitors of ribonucleotide reductase
      (RNR), the rate-limiting enzyme in the synthesis of deoxyribonucleotides. We
      subsequently found that the inhibition of checkpoint kinase 1 (CHK1) increases
      the sensitivity of Ewing sarcoma cells to inhibitors of RNR, such as gemcitabine.
      However, Ewing sarcoma cells exhibit high levels of the CHK1 protein, which may
      represent an adaptive response to elevated levels of endogenous DNA replication
      stress. Consequently, we began this work with the aim of determining the impact
      of CHK1 levels on drug sensitivity, as well as identifying the mechanisms and
      pathways that regulate CHK1 levels in Ewing sarcoma cells. In this report, we
      show that the high levels of the CHK1 protein in Ewing sarcoma cells limit the
      efficacy of CHK1 inhibitors. However, inhibition of mTORC1/2 activates the
      translational repressor 4E-BP1, reduces protein synthesis, and decreases levels
      of the CHK1 protein in Ewing sarcoma cells. Similarly, we identified that the
      CHK1 inhibitor prexasertib also activates 4E-BP1, inhibits protein synthesis, and
      reduces CHK1 protein levels in Ewing sarcoma cells. Moreover, the combination of
      prexasertib and gemcitabine was synergistic in vitro, caused tumor regression in
      vivo, and significantly prolonged mouse survival in a Ewing sarcoma xenograft
      experiment. Overall, our results provide insight into Ewing sarcoma biology and
      support further investigation of the CHK1 pathway as a therapeutic target in
      Ewing sarcoma tumors.

PMID- 30282811
TI  - A Human Ribonuclease Variant and ERK-Pathway Inhibitors Exhibit Highly
      Synergistic Toxicity for Cancer Cells.
AB  - Pancreatic-type ribonucleases (ptRNases) are prevalent secretory enzymes that
      catalyze the cleavage of RNA. Ribonuclease inhibitor (RI) is a cytosolic protein
      that has femtomolar affinity for ptRNases, affording protection from the toxic
      catalytic activity of ptRNases, which can invade human cells. A human ptRNase
      variant that is resistant to inhibition by RI is a cytotoxin that is undergoing a
      clinical trial as a cancer chemotherapeutic agent. We find that the ptRNase and
      protein kinases in the ERK pathway exhibit strongly synergistic toxicity toward
      lung cancer cells (including a KRASG12C variant) and melanoma cells (including
      BRAFV600E variants). The synergism arises from inhibiting the phosphorylation of
      RI and thereby diminishing its affinity for the ptRNase. These findings link
      seemingly unrelated cellular processes, and suggest that the use of a kinase
      inhibitor to unleash a cytotoxic enzyme could lead to beneficial manifestations
      in the clinic.

PMID- 30282814
TI  - Association of Imatinib Plasma Concentration and Single-nucleotide Polymorphisms
      with Adverse Drug Reactions in Patients with Gastrointestinal Stromal Tumors.
AB  - Gastrointestinal stromal tumors (GIST) are the most prevalent mesenchymal tumors
      of the digestive tract. To investigate the association of imatinib mesylate
      plasma concentration with adverse drug reactions (ADRs) and influences of genetic
      polymorphisms on ADRs in GIST patients taking imatinib, a cohort of GIST patients
      consecutively treated with imatinib were included in the observational study.
      Clinical, pathologic and genotype information was recorded at enrollment and
      blood samples were collected at time as design. The plasma concentration of the
      imatinib was detected by LC-MS/MS. A questionnaire was used to evaluate the ADRs
      at each visit. SNPs in 13 genes were analyzed for a possible association with
      ADRs. The mean plasma trough concentration of 129 patients taking imatinib was
      1.45 +/- 0.79 MUg/ml, average peak concentration was 2.63 +/- 1.07 MUg/ml. The
      imatinib concentration in patients treated with 600 mg/day was significantly
      higher than other dosage groups (P < 0.05). The ADRs were mostly mild. Edema,
      vomiting, and fatigue were significantly correlated with imatinib concentration
      (P < 0.05). Mutations of IL13 rs1800925 and CXCL14 rs7716492 were related with
      the incidence of leukopenia and rash in our research, separately (P < 0.05). We
      confirmed that with the increase of imatinib concentration, the incidence of
      edema, vomiting, and fatigue rises as well. Mutations of IL13 rs1800925 and
      CXCL14 rs7716492 may be the promising biomarkers to predict the ADRs of imatinib.
      The results of the study are of guiding significance for the use of imatinib in
      patients with GIST.

PMID- 30282815
TI  - Mast cells and neutrophils mediate peripheral motor pathway degeneration in ALS.
AB  - Neuroinflammation is a recognized pathogenic mechanism underlying motor neuron
      degeneration in amyotrophic lateral sclerosis (ALS), but the inflammatory
      mechanisms influencing peripheral motor axon degeneration remain largely unknown.
      A recent report showed a pathogenic role for c-Kit-expressing mast cells
      mediating inflammation and neuromuscular junction denervation in muscles from
      SOD1G93A rats. Here, we have explored whether mast cells infiltrate skeletal
      muscles in autopsied muscles from ALS patients. We report that degranulating mast
      cells were abundant in the quadriceps muscles from ALS subjects but not in
      controls. Mast cells were associated with myofibers and motor endplates and,
      remarkably, interacted with neutrophils forming large extracellular traps. Mast
      cells and neutrophils were also abundant around motor axons in the extensor
      digitorum longus muscle, sciatic nerve, and ventral roots of symptomatic SOD1G93A
      rats, indicating that immune cell infiltration extends along the entire
      peripheral motor pathway. Postparalysis treatment of SOD1G93A rats with the
      tyrosine kinase inhibitor drug masitinib prevented mast cell and neutrophil
      infiltration, axonal pathology, secondary demyelination, and the loss of type 2B
      myofibers, compared with vehicle-treated rats. These findings provide further
      evidence for a yet unrecognized contribution of immune cells in peripheral motor
      pathway degeneration that can be therapeutically targeted by tyrosine kinase
      inhibitors.

PMID- 30282816
TI  - Prelamin A causes aberrant myonuclear arrangement and results in muscle fiber
      weakness.
AB  - Physiological and premature aging are frequently associated with an accumulation
      of prelamin A, a precursor of lamin A, in the nuclear envelope of various cell
      types. Here, we aimed to underpin the hitherto unknown mechanisms by which
      prelamin A alters myonuclear organization and muscle fiber function. By
      experimentally studying membrane-permeabilized myofibers from various transgenic
      mouse lines, our results indicate that, in the presence of prelamin A, the
      abundance of nuclei and myosin content is markedly reduced within muscle fibers.
      This leads to a concept by which the remaining myonuclei are very distant from
      each other and are pushed to function beyond their maximum cytoplasmic capacity,
      ultimately inducing muscle fiber weakness.

PMID- 30282818
TI  - Maternal high-fat diet results in microbiota-dependent expansion of ILC3s in mice
      offspring.
AB  - Maternal obesity and a high-fat diet (HFD) during the perinatal period have
      documented short- and long-term adverse outcomes for offspring. However, the
      mechanisms of maternal HFD effects on neonatal offspring are unclear. While the
      effects of maternal HFD exposure during pregnancy on the offspring are
      increasingly being appreciated, we do not know if maternal HFD alters the
      microbiota or affects neonatal susceptibility to inflammatory conditions, nor the
      mechanisms involved. In this study, we show that the offspring of mothers exposed
      to HFD develop a unique microbiota, marked by expansion of Firmicutes, and an
      increase in IL-17-producing type 3 innate lymphoid cells (ILC3s). The expansion
      of ILC3s was recapitulated through neocolonization with HFD microbiota alone.
      Further, the HFD offspring were susceptible to a neonatal model of inflammation
      that was reversible with IL-17 blockade. Collectively, these data suggest a
      previously unknown and unique role for ILC3s in the promotion of an early
      inflammatory susceptibility in the offspring of mothers exposed to HFD.

PMID- 30282817
TI  - Gut microbiota-dependent modulation of innate immunity and lymph node remodeling
      affects cardiac allograft outcomes.
AB  - We hypothesized that the gut microbiota influences survival of murine cardiac
      allografts through modulation of immunity. Antibiotic pretreated mice received
      vascularized cardiac allografts and fecal microbiota transfer (FMT), along with
      tacrolimus immunosuppression. FMT source samples were from normal, pregnant
      (immune suppressed), or spontaneously colitic (inflammation) mice.
      Bifidobacterium pseudolongum (B. pseudolongum) in pregnant FMT recipients was
      associated with prolonged allograft survival and lower inflammation and fibrosis,
      while normal or colitic FMT resulted in inferior survival and worse histology.
      Transfer of B. pseudolongum alone resulted in reduced inflammation and fibrosis.
      Stimulation of DC and macrophage lines with B. pseudolongum induced the
      antiinflammatory cytokine IL-10 and homeostatic chemokine CCL19 but induced
      lesser amounts of the proinflammatory cytokines TNFalpha and IL-6. In contrast,
      LPS and Desulfovibrio desulfuricans (D. desulfuricans), more abundant in colitic
      FMT, induced a more inflammatory cytokine response. Analysis of mesenteric and
      peripheral lymph node structure showed that B. pseudolongum gavage resulted in a
      higher laminin alpha4/alpha5 ratio in the lymph node cortical ridge, indicative
      of a suppressive environment, while D. desulfuricans resulted in a lower laminin
      alpha4/alpha5 ratio, supportive of inflammation. Discrete gut bacterial species
      alter immunity and may predict graft outcomes through stimulation of myeloid
      cells and shifts in lymph node structure and permissiveness.

PMID- 30282819
TI  - Ex vivo lung perfusion as a human platform for preclinical small molecule
      testing.
AB  - The acute respiratory distress syndrome (ARDS) causes an estimated 70,000 US
      deaths annually. Multiple pharmacologic interventions for ARDS have been tested
      and failed. An unmet need is a suitable laboratory human model to predictively
      assess emerging therapeutics on organ function in ARDS. We previously
      demonstrated that the small molecule BC1215 blocks actions of a proinflammatory
      E3 ligase-associated protein, FBXO3, to suppress NF-kappaB signaling in animal
      models of lung injury. Ex vivo lung perfusion (EVLP) is a clinical technique that
      maintains lung function for possible transplant after organ donation. We used
      human lungs unacceptable for transplant to model endotoxemic injury with EVLP for
      6 hours. LPS infusion induced inflammatory injury with impaired oxygenation of
      pulmonary venous circulation. BC1215 treatment after LPS rescued oxygenation and
      decreased inflammatory cytokines in bronchoalveolar lavage. RNA sequencing
      transcriptomics from biopsies taken during EVLP revealed robust inflammatory gene
      induction by LPS with a strong signal for NF-kappaB-associated transcripts.
      BC1215 treatment reduced the LPS induction of genes associated with inflammatory
      and host defense gene responses by Gene Ontology (GOterm) and pathways analysis.
      BC1215 also significantly antagonized LPS-mediated NF-kappaB activity. EVLP may
      provide a unique human platform for preclinical study of chemical entities such
      as FBXO3 inhibitors on tissue physiology.

PMID- 30282820
TI  - Reverse electrical remodeling in rats with heart failure and preserved ejection
      fraction.
AB  - Sudden death is the most common mode of exodus in patients with heart failure and
      preserved ejection fraction (HFpEF). Cardiosphere-derived cells (CDCs) reduce
      inflammation and fibrosis in a rat model of HFpEF, improving diastolic function
      and prolonging survival. We tested the hypothesis that CDCs decrease ventricular
      arrhythmias (VAs) and thereby possibly contribute to prolonged survival. Dahl
      salt-sensitive rats were fed a high-salt diet to induce HFpEF. Allogeneic rat
      CDCs (or phosphate-buffered saline as placebo) were injected in rats with echo
      verified HFpEF. CDC-injected HFpEF rats were less prone to VA induction by
      programmed electrical stimulation. Action potential duration (APD) was shortened,
      and APD homogeneity was increased by CDC injection. Transient outward potassium
      current density was upregulated in cardiomyocytes from CDC rats relative to
      placebo, as were the underlying transcript (Kcnd3) and protein (Kv4.3) levels.
      Fibrosis was attenuated in CDC-treated hearts, and survival was increased. Sudden
      death risk also trended down, albeit nonsignificantly. CDC therapy decreased VA
      in HFpEF rats by shortening APD, improving APD homogeneity, and decreasing
      fibrosis. Unlike other stem/progenitor cells, which often exacerbate arrhythmias,
      CDCs reverse electrical remodeling and suppress arrhythmogenesis in HFpEF.

PMID- 30282821
TI  - Somatostatin receptor subtype 5 modifies hypothalamic-pituitary-adrenal axis
      stress function.
AB  - Pituitary corticotroph somatostatin receptor subtype 5 (SSTR5) signals to inhibit
      adrenocorticotrophin (ACTH) secretion. As ACTH deficiency results in attenuated
      adrenal cortisol production and an impaired stress response, we sought to clarify
      the role of SSTR5 in modifying the hypothalamic/pituitary/adrenal (HPA) axis. We
      generated Tg HP5 mice overexpressing SSTR5 in pituitary corticotrophs that
      produce the ACTH precursor proopiomelanocortin (POMC). Basal ACTH and
      corticosterone were similar in HP5 and WT mice, while HP5 mice showed attenuated
      ACTH and corticosterone responses to corticotrophin releasing hormone (CRH). HP5
      mice exhibited attenuated corticosterone responses upon a restraint stress test
      and inflammatory stress following LPS injection, as well as increased anxiety
      like and depressive-like behavior on open field and forced swim tests. Pituitary
      corticotroph CRH receptor subtype 1 (CRHR1) mRNA expression and ACTH responses to
      CRH were also attenuated in HP5 mice. In AtT20 cells stably overexpressing SSTR5,
      CRHR1 expression and cAMP response to CRH were reduced, whereas both were
      increased after SSTR5 KO. In elucidating mechanisms for these observations, we
      show that SSTR5-induced miR-449c suppresses both CRHR1 expression and function.
      We conclude that corticotroph SSTR5 attenuates HPA axis responses via CRHR1
      downregulation, suggesting a role for SSTR5 in the pathogenesis of secondary
      adrenal insufficiency.

PMID- 30282822
TI  - Colonic epithelial miR-31 associates with the development of Crohn's phenotypes.
AB  - BACKGROUND: Crohn's disease (CD) is highly heterogeneous, due in large part to
      variability in cellular processes that underlie the natural history of CD,
      thereby confounding effective therapy. There is a critical need to advance
      understanding of the cellular mechanisms that drive CD heterogeneity. METHODS: We
      performed small RNA sequencing of adult colon tissue from CD and NIBD controls.
      Colonic epithelial cells and immune cells were isolated from colonic tissues, and
      microRNA-31 (miR-31) expression was measured. miR-31 expression was measured in
      colonoid cultures generated from controls and patients with CD. We performed
      small RNA-sequencing of formalin-fixed paraffin-embedded colon and ileum biopsies
      from treatment-naive pediatric patients with CD and controls and collected data
      on disease features and outcomes. RESULTS: Small RNA-sequencing and microRNA
      profiling in the colon revealed 2 distinct molecular subtypes, each with
      different clinical associations. Notably, we found that miR-31 expression was a
      driver of these 2 subtypes and, further, that miR-31 expression was particularly
      pronounced in epithelial cells. Colonoids revealed that miR-31 expression
      differences are preserved in this ex vivo system. In adult patients, low colonic
      miR-31 expression levels at the time of surgery were associated with worse
      disease outcome as measured by need for an end ileostomy and recurrence of
      disease in the neoterminal ileum. In pediatric patients, lower miR-31 expression
      at the time of diagnosis was associated with future development of fibrostenotic
      ileal CD requiring surgeryCONCLUSIONS. These findings represent an important step
      forward in designing more effective clinical trials and developing personalized
      CD therapies. FUNDING: This work was supported by CCF Career Development Award
      (SZS), R01-ES024983 from NIEHS (SZS and TSF), 1R01DK104828-01A1 from NIDDK (SZS
      and TSF), P01-DK094779-01A1 from NIDDK (SZS), P30-DK034987 from NIDDK (SZS), 1-16
      ACE-47 ADA Pathway Award (PS), UNC Nutrition Obesity Research Center Pilot &
      Feasibility Grant P30DK056350 (PS), CCF PRO-KIIDS NETWORK (SZS and PS), UNC CGIBD
      T32 Training Grant from NIDDK (JBB), T32 Training Grant (5T32GM007092-42) from
      NIGMS (MH), and SHARE from the Helmsley Trust (SZS). The UNC Translational
      Pathology Laboratory is supported, in part, by grants from the National Cancer
      Institute (3P30CA016086) and the UNC University Cancer Research Fund (UCRF) (PS).

PMID- 30282824
TI  - Clinical implications of monitoring nivolumab immunokinetics in non-small cell
      lung cancer patients.
AB  - BACKGROUND: The PD-1-blocking antibody nivolumab persists in patients several
      weeks after the last infusion. However, no study has systematically evaluated the
      maximum duration that the antibody persists on T cells or the association between
      this duration and residual therapeutic efficacy or potential adverse events.
      METHODS: To define the duration of binding and residual efficacy of nivolumab
      after discontinuation, we developed a simplified strategy for T cell monitoring
      and used it to analyze T cells from peripheral blood from 11 non-small cell lung
      cancer patients previously treated with nivolumab. To determine the suitability
      of our method for other applications, we compared transcriptome profiles between
      nivolumab-bound and nivolumab-unbound CD8 T cells. We also applied T cell
      monitoring in 2 nivolumab-treated patients who developed progressive lung tumors
      during long-term follow-up. RESULTS: Prolonged nivolumab binding was detected
      more than 20 weeks after the last infusion, regardless of the total number of
      nivolumab infusions (2-15 doses) or type of subsequent treatment, in 9 of the 11
      cases in which long-term monitoring was possible. Ki-67 positivity, a
      proliferation marker, in T cells decreased in patients with progressive disease.
      Transcriptome profiling identified the signals regulating activation of nivolumab
      bound T cells, which may contribute to nivolumab resistance. In 2 patients who
      restarted nivolumab, T cell proliferation markers exhibited the opposite trend
      and correlated with clinical response. CONCLUSIONS: Although only a few samples
      were analyzed, our strategy of monitoring both nivolumab binding and Ki-67 in T
      cells might help determine residual efficacy under various types of concurrent or
      subsequent treatment. TRIAL REGISTRATION: University Hospital Medical Information
      Network Clinical Trials Registry, UMIN000024623. FUNDING: This work was supported
      by Japan Society for the Promotion of Science KAKENHI (JP17K16045, JP18H05282,
      and JP15K09220), Japan Agency for Medical Research and Development
      (JP17cm0106310, JP18cm0106335 and JP18cm059042), and Core Research for
      Evolutional Science and Technology (JPMJCR16G2).

PMID- 30282825
TI  - SYK inhibitor entospletinib prevents ocular and skin GVHD in mice.
AB  - Graft-versus-host disease (GVHD) is a major complication of hematopoietic stem
      cell transplantation (HCT). The tyrosine kinase SYK contributes to both acute and
      chronic GVHD development, making it an attractive target for GVHD prevention.
      Entospletinib (ENTO) is a second-generation highly selective SYK inhibitor with a
      high safety profile. Potential utility of ENTO as GVHD prophylaxis in patients
      was examined using a preclinical mouse model of eye and skin GVHD and ENTO
      compounded chow. We found that early SYK inhibition improved blood immune cell
      reconstitution in GVHD mice and prolonged survival, with 60% of mice surviving to
      day +120 compared with 10% of mice treated with placebo. Compared with mice
      receiving placebo, mice receiving ENTO had dramatic improvements in clinical eye
      scores, alopecia scores, and skin scores. Infiltrating SYK+ cells expressing B220
      or F4/80, resembling SYK+ cells found in lichenoid skin lesions of chronic GVHD
      patients, were abundant in the skin of placebo mice but were rare in ENTO-treated
      mice. Thus, ENTO given early after HCT safely prevented GVHD.

PMID- 30282823
TI  - Arginine vasopressin infusion is sufficient to model clinical features of
      preeclampsia in mice.
AB  - Copeptin, a marker of arginine vasopressin (AVP) secretion, is elevated
      throughout human pregnancies complicated by preeclampsia (PE), and AVP infusion
      throughout gestation is sufficient to induce the major phenotypes of PE in mice.
      Thus, we hypothesized a role for AVP in the pathogenesis of PE. AVP infusion into
      pregnant C57BL/6J mice resulted in hypertension, renal glomerular endotheliosis,
      intrauterine growth restriction, decreased placental growth factor (PGF), altered
      placental morphology, placental oxidative stress, and placental gene expression
      consistent with human PE. Interestingly, these changes occurred despite a lack of
      placental hypoxia or elevations in placental fms-like tyrosine kinase-1 (FLT1).
      Coinfusion of AVP receptor antagonists and time-restricted infusion of AVP
      uncovered a mid-gestational role for the AVPR1A receptor in the observed renal
      pathologies, versus mid- and late-gestational roles for the AVPR2 receptor in the
      blood pressure and fetal phenotypes. These findings demonstrate that AVP is
      sufficient to initiate phenotypes of PE in the absence of placental hypoxia, and
      indicate that AVP may mechanistically (independently, and possibly
      synergistically with hypoxia) contribute to the development of clinical signs of
      PE in specific subtypes of human PE. Additionally, they identify divergent and
      gestational time-specific signaling mechanisms that mediate the development of PE
      phenotypes in response to AVP.

PMID- 30282826
TI  - The DILfrequency study is an adaptive trial to identify optimal IL-2 dosing in
      patients with type 1 diabetes.
AB  - BACKGROUND: Type 1 diabetes (T1D) results from loss of immune regulation, leading
      to the development of autoimmunity to pancreatic beta cells, involving
      autoreactive T effector cells (Teffs). Tregs, which prevent autoimmunity, require
      IL-2 for maintenance of immunosuppressive functions. Using a response-adaptive
      design, we aimed to determine the optimal regimen of aldesleukin (recombinant
      human IL-2) to physiologically enhance Tregs while limiting expansion of Teffs.
      METHODS: DILfrequency is a nonrandomized, open-label, response-adaptive study of
      participants, aged 18-70 years, with T1D. The initial learning phase allocated 12
      participants to 6 different predefined regimens. Then, 3 cohorts of 8
      participants were sequentially allocated dose frequencies, based on repeated
      interim analyses of all accumulated trial data. The coprimary endpoints were
      percentage change in Tregs and Teffs and CD25 (alpha subunit of the IL-2
      receptor) expression by Tregs, from baseline to steady state. RESULTS: Thirty
      eight participants were enrolled, with thirty-six completing treatment. The
      optimal regimen to maintain a steady-state increase in Tregs of 30% and CD25
      expression of 25% without Teff expansion is 0.26 * 106 IU/m2 (95% CI -0.007 to
      0.485) every 3 days. Tregs and CD25 were dose-frequency responsive, Teffs were
      not. The commonest adverse event was injection site reaction (464 of 694 events).
      CONCLUSIONS: Using a response-adaptive design, aldesleukin treatment can be
      optimized. Our methodology can generally be employed to immediately access proof
      of mechanism, thereby leading to more efficient and safe drug development. TRIAL
      REGISTRATION: International Standard Randomised Controlled Trial Number Register,
      ISRCTN40319192; ClinicalTrials.gov, NCT02265809. FUNDING: Sir Jules Thorn Trust,
      the Swiss National Science Foundation, Wellcome, JDRF, and NIHR Cambridge
      Biomedical Research Centre.

PMID- 30282828
TI  - Mucosal-associated invariant and gammadelta T cell subsets respond to initial
      Mycobacterium tuberculosis infection.
AB  - Innate immune responses that control early Mtb infection are poorly understood,
      but understanding these responses may inform vaccination and immunotherapy
      strategies. Innate T cells that respond to conserved bacterial ligands such as
      mucosal-associated invariant T (MAIT) and gammadelta T cells are prime candidates
      to mediate these early innate responses but have not been examined in subjects
      who have been recently exposed to Mtb. We recruited a cohort living in the same
      household with an active tuberculosis (TB) case and examined the abundance and
      functional phenotypes of 3 innate T cell populations reactive to M. tuberculosis:
      gammadelta T, invariant NK T (iNKT), and MAIT cells. Both MAIT and gammadelta T
      cells from subjects with Mtb exposure display ex vivo phenotypes consistent with
      recent activation. However, both MAIT and gammadelta T cell subsets have distinct
      response profiles, with CD4+ MAIT and gammadelta T cells accumulating after
      infection. Examination of exposed but uninfected contacts demonstrates that
      resistance to initial infection is accompanied by robust MAIT cell CD25
      expression and granzyme B production coupled with a depressed CD69 and IFNgamma
      response. Finally, we demonstrate that MAIT cell abundance and function correlate
      with the abundance of specific gut microbes, suggesting that responses to initial
      infection may be modulated by the intestinal microbiome.

PMID- 30282829
TI  - Dual TLR2 and TLR7 agonists as HIV latency-reversing agents.
AB  - The presence of a reservoir of latently infected cells in HIV-infected patients
      is a major barrier towards finding a cure. One active cure strategy is to find
      latency-reversing agents that induce viral reactivation, thus leading to immune
      cell recognition and elimination of latently infected cells, known as the shock
      and-kill strategy. Therefore, the identification of molecules that reactivate
      latent HIV and increase immune activation has the potential to further these
      strategies into the clinic. Here, we characterized synthetic molecules composed
      of a TLR2 and a TLR7 agonist (dual TLR2/7 agonists) as latency-reversing agents
      and compared their activity with that of the TLR2 agonist Pam2CSK4 and the TLR7
      agonist GS-9620. We found that these dual TLR2/7 agonists reactivate latency by 2
      complementary mechanisms. The TLR2 component reactivates HIV by inducing NF
      kappaB activation in memory CD4+ T cells, while the TLR7 component induces the
      secretion of TNF-alpha by monocytes and plasmacytoid dendritic cells, promoting
      viral reactivation in CD4+ T cells. Furthermore, the TLR2 component induces the
      secretion of IL-22, which promotes an antiviral state and blocks HIV infection in
      CD4+ T cells. Our study provides insight into the use of these agonists as a
      multipronged approach targeting eradication of latent HIV.

PMID- 30282830
TI  - Myeloid HO-1 modulates macrophage polarization and protects against ischemia
      reperfusion injury.
AB  - Macrophages polarize into heterogeneous proinflammatory M1 and antiinflammatory
      M2 subtypes. Heme oxygenase 1 (HO-1) protects against inflammatory processes such
      as ischemia-reperfusion injury (IRI), organ transplantation, and atherosclerosis.
      To test our hypothesis that HO-1 regulates macrophage polarization and protects
      against IRI, we generated myeloid-specific HO-1-knockout (mHO-1-KO) and 
      transgenic (mHO-1-Tg) mice, with deletion or overexpression of HO-1, in various
      macrophage populations. Bone marrow-derived macrophages (BMDMs) from mHO-1-KO
      mice, treated with M1-inducing LPS or M2-inducing IL-4, exhibited increased mRNA
      expression of M1 (CXCL10, IL-1beta, MCP1) and decreased expression of M2 (Arg1
      and CD163) markers as compared with controls, while BMDMs from mHO-1-Tg mice
      displayed the opposite. A similar pattern was observed in the hepatic M1/M2
      expression profile in a mouse model of liver IRI. mHO-1-KO mice displayed
      increased hepatocellular damage, serum AST/ALT levels, Suzuki's histological
      score of liver IRI, and neutrophil and macrophage infiltration, while mHO-1-Tg
      mice exhibited the opposite. In human liver transplant biopsies, subjects with
      higher HO-1 levels showed lower expression of M1 markers together with decreased
      hepatocellular damage and improved outcomes. In conclusion, myeloid HO-1
      expression modulates macrophage polarization, and protects against liver IRI, at
      least in part by favoring an M2 phenotype.

PMID- 30282827
TI  - Fat fibrosis: friend or foe?
AB  - At the simplest level, obesity is the manifestation of an imbalance between
      caloric intake and expenditure; however, the pathophysiological mechanisms that
      govern the development of obesity and associated complications are enormously
      complex. Fibrosis within the adipose tissue compartment is one such factor that
      may influence the development of obesity and/or obesity-related comorbidities.
      Furthermore, the functional consequences of adipose tissue fibrosis are a matter
      of considerable debate, with evidence that fibrosis serves both adaptive and
      maladaptive roles. Tissue fibrosis itself is incompletely understood, and
      multiple cellular and molecular pathways are involved in the development,
      maintenance, and resolution of the fibrotic state. Within the context of obesity,
      fibrosis influences molecular and cellular events that relate to adipocytes,
      inflammatory cells, inflammatory mediators, and supporting adipose stromal
      tissue. In this Review, we explore what is known about the interplay between the
      development of adipose tissue fibrosis and obesity, with a view toward future
      investigative and therapeutic avenues.

PMID- 30282831
TI  - A sheep model of cystic fibrosis generated by CRISPR/Cas9 disruption of the CFTR
      gene.
AB  - Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF
      transmembrane conductance regulator (CFTR) gene. The major cause of limited life
      span in CF patients is progressive lung disease. CF models have been generated in
      4 species (mice, rats, ferrets, and pigs) to enhance our understanding of the CF
      pathogenesis. Sheep may be a particularly relevant animal to model CF in humans
      due to the similarities in lung anatomy and development in the two species. Here,
      we describe the generation of a sheep model for CF using CRISPR/Cas9 genome
      editing and somatic cell nuclear transfer (SCNT) techniques. We generated cells
      with CFTR gene disruption and used them for production of CFTR-/- and CFTR+/-
      lambs. The newborn CFTR-/- sheep developed severe disease consistent with CF
      pathology in humans. Of particular relevance were pancreatic fibrosis, intestinal
      obstruction, and absence of the vas deferens. Also, substantial liver and
      gallbladder disease may reflect CF liver disease that is evident in humans. The
      phenotype of CFTR-/- sheep suggests this large animal model will be a useful
      resource to advance the development of new CF therapeutics. Moreover, the
      generation of specific human CF disease-associated mutations in sheep may advance
      personalized medicine for this common genetic disorder.

PMID- 30282832
TI  - Chronic linaclotide treatment reduces colitis-induced neuroplasticity and
      reverses persistent bladder dysfunction.
AB  - Irritable bowel syndrome (IBS) patients suffer from chronic abdominal pain and
      extraintestinal comorbidities, including overactive bladder (OAB) and
      interstitial cystitis/painful bladder syndrome (IC-PBS). Mechanistic
      understanding of the cause and time course of these comorbid symptoms is lacking,
      as are clinical treatments. Here, we report that colitis triggers
      hypersensitivity of colonic afferents, neuroplasticity of spinal cord circuits,
      and chronic abdominal pain, which persists after inflammation. Subsequently, and
      in the absence of bladder pathology, colonic hypersensitivity induces persistent
      hypersensitivity of bladder afferent pathways, resulting in bladder-voiding
      dysfunction, indicative of OAB/IC-PBS. Daily administration of linaclotide, a
      guanylate cyclase-C (GC-C) agonist that is restricted to and acts within the
      gastrointestinal tract, reverses colonic afferent hypersensitivity, reverses
      neuroplasticity-induced alterations in spinal circuitry, and alleviates chronic
      abdominal pain in mice. Intriguingly, daily linaclotide administration also
      reverses persistent bladder afferent hypersensitivity to mechanical and chemical
      stimuli and restores normal bladder voiding. Linaclotide itself does not inhibit
      bladder afferents, rather normalization of bladder function by daily linaclotide
      treatment occurs via indirect inhibition of bladder afferents via reduced
      nociceptive signaling from the colon. These data support the concepts that cross
      organ sensitization underlies the development and maintenance of visceral
      comorbidities, while pharmaceutical treatments that inhibit colonic afferents may
      also improve urological symptoms through common sensory pathways.

PMID- 30282834
TI  - Thrombocytopenia is associated with severe retinopathy of prematurity.
AB  - Retinopathy of prematurity (ROP) is characterized by abnormal retinal
      neovascularization in response to vessel loss. Platelets regulate angiogenesis
      and may influence ROP progression. In preterm infants, we assessed ROP and
      correlated with longitudinal postnatal platelet counts (n = 202). Any episode of
      thrombocytopenia (<100 * 109/l) at >=30 weeks postmenstrual age (at onset of ROP)
      was independently associated with severe ROP, requiring treatment. Infants with
      severe ROP also had a lower weekly median platelet count compared with infants
      with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP,
      platelet counts were lower at P17 (peak neovascularization) versus controls.
      Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet
      depletion increased neovascularization. Platelet transfusion decreased retinal of
      vascular endothelial growth factor A (VEGFA) mRNA and protein expression;
      platelet depletion increased retinal VEGFA mRNA and protein expression. Resting
      platelets with intact granules reduced neovascularization, while thrombin
      activated degranulated platelets did not. These data suggest that platelet
      releasate has a local antiangiogenic effect on endothelial cells to exert a
      downstream suppression of VEGFA in neural retina. Low platelet counts during the
      neovascularization phase in ROP is significantly associated with the development
      of severe ROP in preterm infants. In a murine model of retinopathy, platelet
      transfusion during the period of neovascularization suppressed retinopathy.

PMID- 30282835
TI  - Treatment of Streptococcus pneumoniae otitis media in a chinchilla model by
      transtympanic delivery of antibiotics.
AB  - Otits media (OM) is the most frequent indication for antimicrobial prescription
      to US children. Streptococcus pneumoniae (S. pneumoniae) remains one of the most
      common pathogens causing OM. Successful eradication of S. pneumoniae in the
      middle ear can be achieved by adhering to a 7-10 day regimen of oral antibiotics.
      However, oral drug administration is challenging for parents. Lack of adherence
      has been associated with treatment failure or early relapse. To overcome this
      challenge, we used a noninvasive formulation to achieve high transtympanic
      antibiotic flux and cured S. pneumoniae OM in chinchillas. The formulation
      consists of a thermosensitive in situ gelling hydrogel, chemical permeation
      enhancers, and an antibiotic. The direct transport of drugs into the middle ear
      produced high concentrations of ciprofloxacin (in the range of hundreds of
      micrograms per milliliter) within the first 24 hours of administration. Drug
      concentrations above the minimum inhibitory concentration (MIC) for S. pneumoniae
      were sustained throughout the 7-day treatment. S. pneumoniae OM in a chinchilla
      model was successfully eradicated, without causing tissue toxicity. Transtympanic
      delivery minimized systemic drug exposure, as evidenced by undetectable levels in
      blood, measured by high-performance liquid chromatography.

PMID- 30282833
TI  - Splicing modulation sensitizes chronic lymphocytic leukemia cells to venetoclax
      by remodeling mitochondrial apoptotic dependencies.
AB  - The identification of targetable vulnerabilities in the context of therapeutic
      resistance is a key challenge in cancer treatment. We detected pervasive aberrant
      splicing as a characteristic feature of chronic lymphocytic leukemia (CLL),
      irrespective of splicing factor mutation status, which was associated with
      sensitivity to the spliceosome modulator, E7107. Splicing modulation affected CLL
      survival pathways, including members of the B cell lymphoma-2 (BCL2) family of
      proteins, remodeling antiapoptotic dependencies of human and murine CLL cells.
      E7107 treatment decreased myeloid cell leukemia-1 (MCL1) dependence and increased
      BCL2 dependence, sensitizing primary human CLL cells and venetoclax-resistant CLL
      like cells from an EMU-TCL1-based adoptive transfer murine model to treatment
      with the BCL2 inhibitor venetoclax. Our data provide preclinical rationale to
      support the combination of venetoclax with splicing modulators to reprogram
      apoptotic dependencies in CLL for treating venetoclax-resistant CLL cases.

PMID- 30282838
TI  - Loss of ACAT1 Attenuates Atherosclerosis Aggravated by Loss of NCEH1 in Bone
      Marrow-Derived Cells.
AB  - AIM: Acyl-CoA cholesterol acyltransferase 1 (ACAT1) esterifies free cholesterol
      to cholesteryl esters (CE), which are subsequently hydrolyzed by neutral
      cholesterol ester hydrolase 1 (NCEH1). The elimination of ACAT1 in vitro reduces
      the amounts of CE accumulated in Nceh1-deficient macrophages. The present study
      aimed at examining whether the loss of ACAT1 attenuates atherosclerosis which is
      aggravated by the loss of NCEH1 in vivo. METHODS: Low density lipoprotein
      receptor (Ldlr)-deficient mice were transplanted with bone marrow from wild-type
      mice and mice lacking ACAT1, NCEH1, or both. The four types of mice were fed a
      high-cholesterol diet and, then, were examined for atherosclerosis. RESULTS: The
      cross-sectional lesion size of the recipients of Nceh1-deficient bone marrow was
      1.6-fold larger than that of the wild-type bone marrow. The lesions of the
      recipients of Nceh1-deficient bone marrow were enriched with MOMA2-positive
      macrophages compared with the lesions of the recipients of the wild-type bone
      marrow. The size and the macrophage content of the lesions of the recipients of
      bone marrow lacking both ACAT1 and NCEH1 were significantly smaller than the
      recipients of the Nceh1-deficient bone marrow, indicating that the loss of ACAT1
      decreases the excess CE in the Nceh1-deficient lesions. The collagen-rich and/or
      mucin-rich areas and en face lesion size were enlarged in the recipients of the
      Acat1-/- bone marrow compared with those of the recipients of the WT bone marrow.
      CONCLUSION: The loss of ACAT1 in bone marrow-derived cells attenuates
      atherosclerosis, which is aggravated by the loss of NCEH1, corroborating the in
      vitro functions of ACAT1 (formation of CE) and NCEH1 (hydrolysis of CE).

PMID- 30282836
TI  - High-throughput T cell receptor sequencing identifies clonally expanded CD8+ T
      cell populations in alopecia areata.
AB  - Alopecia areata (AA) is an autoimmune disease in which cytotoxic T cells
      specifically target growing hair follicles. We used high-throughput TCR
      sequencing in the C3H/HeJ mouse model of AA and in human AA patients to gain
      insight into pathogenic T cell populations and their dynamics, which revealed
      clonal CD8+ T cell expansions in lesional skin. In the C3H/HeJ model, we observed
      interindividual sharing of TCRbeta chain protein sequences, which strongly
      supports a model of antigenic drive in AA. The overlap between the lesional TCR
      repertoire and a population of CD8+NKG2D+ T cells in skin-draining lymph nodes
      identified this subset as pathogenic effectors. In AA patients, treatment with
      the oral JAK inhibitor tofacitinib resulted in a decrease in clonally expanded
      CD8+ T cells in the scalp but also revealed that many expanded lesional T cell
      clones do not completely disappear from either skin or blood during treatment
      with tofacitinib, which may explain in part the relapse of disease after stopping
      treatment.

PMID- 30282839
TI  - Palladium-Catalyzed C-H Heteroarylation of 2,5-Disubstituted Imidazoles.
AB  - We developed a palladium-catalyzed C-H N-heteroarylation of N-protected-2,5
      disubstituted imidazoles at the C4-position using N-heteroaryl halides as a
      coupling partner. Intensive reaction condition screening led us to identify
      fluorinated bathophenanthroline 7 as the optimum ligand for the palladium
      catalyst. This reaction will enhance lead optimization of drug candidates by
      facilitating the synthesis of heterobiaryl compounds containing an imidazole
      ring.

PMID- 30282837
TI  - Enhanced detection of neoantigen-reactive T cells targeting unique and shared
      oncogenes for personalized cancer immunotherapy.
AB  - Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILs) targeting
      neoantigens can mediate tumor regression in selected patients with metastatic
      epithelial cancer. However, effectively identifying and harnessing neoantigen
      reactive T cells for patient treatment remains a challenge and it is unknown
      whether current methods to detect neoantigen-reactive T cells are missing
      potentially clinically relevant neoantigen reactivities. We thus investigated
      whether the detection of neoantigen-reactive TILs could be enhanced by enriching
      T cells that express PD-1 and/or T cell activation markers followed by microwell
      culturing to avoid overgrowth of nonreactive T cells. In 6 patients with
      metastatic epithelial cancer, this method led to the detection of CD4+ and CD8+ T
      cells targeting 18 and 1 neoantigens, respectively, compared with 6 and 2
      neoantigens recognized by CD4+ and CD8+ T cells, respectively, when using our
      standard TIL fragment screening approach. In 2 patients, no recognition of
      mutated peptides was observed using our conventional screen, while our high
      throughput approach led to the identification of 5 neoantigen-reactive T cell
      receptors (TCRs) against 5 different mutations from one patient and a highly
      potent MHC class II-restricted KRASG12V-reactive TCR from a second patient. In
      addition, in a metastatic tumor sample from a patient with serous ovarian cancer,
      we isolated 3 MHC class II-restricted TCRs targeting the TP53G245S hot-spot
      mutation. In conclusion, this approach provides a highly sensitive platform to
      isolate clinically relevant neoantigen-reactive T cells or their TCRs for cancer
      treatment.

PMID- 30282840
TI  - Latent bovine herpesvirus 1 and 5 in milk from naturally infected dairy cattle.
AB  - Bovine herpesvirus 1 and 5 (BoHV-1 and -5) are antigenically and genetically
      related and can establish latent infection. We aimed to analyze the applicability
      of the milk sample to detect latently BoHV-infected cattle. BoHV-1 non-vaccinated
      clinically healthy cows from five dairy cattle herds (herd 1, n=24; herd 2, n=39;
      herd 3, n=39; herd 4, n=36; herd 5, n=70) were studied. We confirmed the presence
      of BoHV-1, and for the first time, BoHV-5 in the milk of naturally infected dairy
      cattle.

PMID- 30282841
TI  - Detection of neutralizing antibody against porcine epidemic diarrhea virus in
      subclinically infected finishing pigs.
AB  - The purpose of this study was to detect porcine epidemic diarrhea virus (PEDV)
      subclinically infected pigs shipped from non-case farms to slaughterhouses.
      Systematic sampling was conducted at two slaughterhouses. A total of 1,556 blood
      samples were collected from 80 case and non-case farms from pigs over 6 months
      old. Blood samples were centrifuged to obtain sera. Serial serum dilutions were
      subjected to serological examination for PEDV presence using Neutralization test
      (NT). The cut-off titer was set at titer of 1:2 dilution and farms with at least
      one positive sample in duplicate were classified as PED-positive farms. Several
      non-case farms (9.4%, 6/64) and 100% (16/16) of the case farms were indeed
      positive for PEDV. The proportion of seropositive animals from case farms was
      63.7%, significantly different from that of non-case farms (4.3%, P<0.05). In
      both case and non-case farms, the proportion of seropositive animals in farrow-to
      finish farms was significantly higher than in wean-to-finish farms (P<0.05).
      Seropositive animals in non-case farms were detected by NT in a sero-survey by
      sampling at slaughterhouses. Therefore, subclinically infected pigs should be
      considered prior to shipment.

PMID- 30282843
TI  - Measurement of visual acuity in Beagle dog by visual evoked potential with
      pattern stimulation.
AB  - We tried measurement of visual acuity in laboratory beagle using pattern stimulus
      visual evoked potential (P-VEP). We recorded P-VEP in 6 beagles which were
      corrected refractive power. The stimulus pattern size was 1.22 mm. The testing
      distance were 0.5, 1.0, and 2.0 m. The visual angles and spatial frequency were
      calculated from stimulus pattern size and distance. In all subjects, P-VEP was
      clearly recorded in all testing distance, and this result means that the eye
      could recognized grid pattern on the stimulus monitor. When stimulus monitor was
      set up 2.0 m, spatial frequency was 14.29 cpd. From our results, it was founded
      that the visual acuity in laboratory beagle which was corrected refractive power
      was 14.29 cpd and more.

PMID- 30282842
TI  - Glycerol induces early fibrosis in regenerating rat skeletal muscle.
AB  - Glycerol has been recently used to induce muscle adiposity in mice. However, its
      effects on the rat muscles have not been investigated previously. Therefore, we
      investigated the regeneration outcomes of rat muscles following glycerol-induced
      injury at different time points. Glycerol injection induced myofiber degeneration
      with extensive inflammatory infiltration on day 4 followed by appearance of
      regenerating myotubes on day 7 after injury without adipocyte infiltration.
      Meanwhile, a significant collagen deposition at early stage of regeneration that
      increased together with persistent inflammatory infiltration up to day 14 after
      injury indicates impaired regeneration. In conclusion, glycerol injury in rats is
      more suitable as a fibrosis-inducing model than in mice due to earlier and higher
      accumulation of fibrous tissue with lacking adipogenesis.

PMID- 30282844
TI  - Sleep Disturbance and Hyperactivity Detected by Actigraphy in Rats with Allergic
      Rhinitis or Attention-Deficit Hyperactivity Disorder.
AB  - Actigraphy is an easy and noninvasive method used to monitor human ultradian
      cycles. However, to our knowledge, it has been not applied to experiments with
      rodents. Therefore, using actigraphy, we assessed the ultradian cycles and
      behavior of rats. Rats with or without allergic rhinitis wore an actigraphy
      device, and triaxial acceleration was recorded. The counts that represent
      physical activity were lower from 8:00 to 20:00 than those from 20:00 to 8:00 in
      control rats, suggesting that their sleep phase was from 8:00 to 20:00 and their
      awake phase from 20:00 to 8:00. The counts from 8:00 to 10:00 were significantly
      higher in allergic rhinitis rats than in control rats (p < 0.01), suggesting the
      presence of difficulty with sleep induction in rats with allergic rhinitis. The
      counts from 18:00 to 20:00 were also significantly higher in allergic rhinitis
      rats than in control rats (p < 0.05), suggesting the presence of early awakening
      in rats with allergic rhinitis. Moreover, the counts were significantly higher in
      allergic rhinitis rats than in control rats from 20:00 to 8:00. These results
      suggest that rats with allergic rhinitis experienced hyperactivity disorder
      during the daytime. Additionally, hyperreactivity and difficulty with sleep
      induction were observed in 6-hydroxydopamine-lesioned rats, an animal model of
      attention-deficit hyperactivity disorder. This study shows for the first time
      that actigraphy can be successfully used for behavioral analysis in rodents.
      These rat models could be useful for analyzing the mechanisms involved in sleep
      disturbances and hyperactivity disorder.

PMID- 30282845
TI  - Vaccination Status and Antibody Titers against Rubella and Measles among Japanese
      Female College Students Majoring in Childcare between 2015 and 2018.
AB  - In 2014, for the protection of medical workers against measles and rubella
      infection, the Japanese Society for Infection Prevention and Control (JSIPC)
      recommended either maintaining antibody titers of seroprotective range or two
      dose vaccination. JSIPC defined antibody titers into 3 ranges: seroprotective as
      expected prevention of infection, seronegative as under detection levels, and
      seropositive as antibody titers ranged between seronegative and seroprotective.
      This study aimed to explore the association between the number of vaccine doses
      received and the antibody titers against measles and rubella among Japanese
      college students majoring in childcare. A total of 841 female students with no
      history of measles or rubella were serologically screened at the time of college
      admission between 2015 and 2018. All 841 students had been vaccinated against
      measles; 738 (87.8%) received two doses of the measles vaccine and 103 (12.2%)
      received one dose. Likewise, 839 students, except for two, had been vaccinated
      against rubella; 719 (85.7%) received two doses of the rubella vaccine and 120
      (14.3%) received one dose. We thus found that 107 students (12.7%) were
      seropositive for measles-specific IgG and 731 (86.9%) attained seroprotective
      titers. By contrast, in case of rubella-specific IgG, only 462 students (55.1%)
      attained seroprotective titers, and 371 students (44.1%) were seropositive. The
      two students without receiving rubella vaccination were classified as
      seronegative. In conclusion, despite that > 85% of students surveyed had received
      two doses of measles and rubella vaccines, a substantial number of students
      remain susceptible to measles and especially rubella at the time of college
      admission.

PMID- 30282846
TI  - Food aversion learning based on voluntary running in non-deprived rats: a
      technique for establishing aversive conditioning with minimized discomfort.
AB  - This article presents an experimental preparation for establishing conditioned
      food aversion (CFA) by voluntary wheel running in rats with laboratory chow and
      water freely available. In Experiment 1, unfamiliar food (raisins) was avoided by
      rats when they first encountered it. This neophobic food avoidance was habituated
      by repeated tests; the rats gradually increased their raisin consumption.
      However, the consumption remained suppressed in rats that accessed the raisins
      after wheel running. This finding implies that running yielded CFA, which
      suppressed consumption of the unfamiliar food rather than increasing it. Because
      running generated kaolin clay ingestion, which is a behavioral marker of nausea,
      it is suggested that the running-based CFA was mediated by weak gastrointestinal
      discomfort. Experiment 2 supported the claim that the suppressed consumption is
      due to running-based CFA by showing the specificity of food suppression.
      Demonstration of CFA based on voluntary activity in non-deprived rats will
      contribute to basic research on learning and memory as an alternative technique
      for studying aversive conditioning with minimized discomfort in animals.

PMID- 30282847
TI  - Emerging Role of Plasma Membranes in Vascular Endothelial Mechanosensing.
AB  - Vascular endothelial cells (ECs) maintain circulatory system homeostasis by
      changing their functions in response to changes in hemodynamic forces, including
      shear stress and stretching. However, it is unclear how ECs sense changes in
      shear stress and stretching and transduce these changes into intracellular
      biochemical signals. The plasma membranes of ECs have recently been shown to
      respond to shear stress and stretching differently by rapidly changing their
      lipid order, fluidity, and cholesterol content. Such changes in the membranes'
      physical properties trigger the activation of membrane receptors and cell
      responses specific to each type of force. Artificial lipid-bilayer membranes show
      similar changes in lipid order in response to shear stress and stretching,
      indicating that they are physical phenomena rather than biological reactions.
      These findings suggest that the plasma membranes of ECs act as mechanosensors; in
      response to mechanical forces, they first alter their physical properties,
      modifying the conformation and function of membrane proteins, which then
      activates downstream signaling pathways. This new appreciation of plasma
      membranes as mechanosensors could help to explain the distinctive features of
      mechanotransduction in ECs involving shear stress and stretching, which activate
      a variety of membrane proteins and multiple signal transduction pathways almost
      simultaneously.

PMID- 30282848
TI  - Validation of Conventional Thromboembolic Risk Factors in a Korean Atrial
      Fibrillation Population - Suggestion for a Novel Scoring System, CHA2DS2-VAK.
AB  - BACKGROUND: There is little evidence that focuses on the ethnic variability of
      clinical risk factors for thromboembolism (TE) in atrial fibrillation (AF). We
      aimed to investigate the effect of each traditional risk factor in the Korean AF
      population. Methods and Results: Medical records of 12,876 consecutive patients
      (aged >18 years) newly diagnosed and followed up with non-valvular AF from 2000
      to 2013 were reviewed. TE events, including ischemic stroke and systemic
      embolism, were investigated for risk factor validation. Among the total of 12,876
      patients, 1,390 (10.8%) had TE events. In univariate/multivariate analysis
      adjusting for clinical factors and antithrombotic medications, traditional risk
      factors included in the CHA2DS2-VASc scheme showed statistical significance,
      except for female sex, which was not a predictor of events. Additionally, chronic
      kidney disease (CKD; hazard ratio 1.62, P<0.001) was shown to be an independent
      predictor of TE events. Based on the analysis, we developed a novel
      stratification system, CHA2DS2-VAK, omitting the female sex category and adding
      CKD. The new scoring system showed greater discrimination in event rates between
      score 0 and 1 patients. CONCLUSIONS: Female sex was not associated with TE events
      in a Korean non-valvular AF population. The novel CHA2DS2-VAK scoring system,
      with substitution of CKD for female sex, might be more appropriate for the Korean
      population.

PMID- 30282849
TI  - Austin Flint Murmur.

PMID- 30282850
TI  - Metabolic Profiling of the Hippocampus of Rats Experiencing Nicotine-Withdrawal
      Symptoms.
AB  - Nicotine-withdrawal symptoms have been indicated as a possible risk factor for
      neuropsychiatric events, such as depression and suicide, during use of smoking
      cessation drugs. We aimed to investigate whether the results of the metabolomic
      analysis of the rat brain reflect nicotine-withdrawal symptoms. We also aimed to
      investigate the relative changes in each metabolite in the brains of rats with
      nicotine-withdrawal symptoms. We created rats experiencing nicotine-withdrawal
      symptoms through repeat administration of nicotine followed by a 12-h withdrawal
      period, and rats recovered from nicotine-withdrawal symptoms followed by an 18-h
      withdrawal period. We then implemented brain metabolic profiling by combining
      high-resolution magic-angle spinning 1H-NMR spectroscopy with partial least
      square discriminant analysis (PLS-DA). We found that metabolic profiling of the
      brain reflects the state during nicotine-withdrawal symptoms and the state after
      recovery from nicotine-withdrawal symptoms. Additionally, N-acetylaspartate and
      glutamate increased and aspartate, gamma-aminobutyric acid (GABA), and creatine
      decreased in the hippocampus of rats experiencing nicotine-withdrawal symptoms.
      Therefore, it is suggested that neurogenesis and neuronal differentiation could
      be changed and abnormal energy metabolism could occur in the hippocampus during
      nicotine-withdrawal symptoms.

PMID- 30282851
TI  - Evaluation of Tumor Tissue Fixation Effects of Formulation Modified Mohs Pastes
      in Mice and Their Water-Absorbing Properties.
AB  - Mohs paste (MP) is a hospital preparation containing zinc hydrochloride and zinc
      oxide starch. It is a topical medication used to fixate tissues for the removal
      of inoperable skin tumors and the management of hemorrhage and exudates, and to
      prevent foul odor resulting from secondary infections. However, it has problems,
      such as changes in hardness and viscoelasticity with time and liquefaction by
      exudate. It has been reported that the modified MP with D-sorbitol (S-MP) and the
      modified MP using the cellulose instead of starch (C-MP) have excellent
      physicochemical stability and better handling than original MP (O-MP). In this
      study, the effect of prescription improvement of MP on the pharmacological effect
      was examined with reference to water absorbing property, and its tumor tissue
      invasion fixation depth as an indicator. In the S-MP and C-MP, the amounts of
      water absorption did not differ significantly from those in the O-MP. The
      hardness of S-MP was decreased and liquefied like O-MP after absorbing water. In
      contrast, C-MP retained its form even after water absorption. The subcutaneous
      tumors in mice treated with modified MP formulations were measured for invasion
      fixation depth at 6 and 24 h after application. And the tissue status was
      observed using computed tomography. In all MPs, invasion fixation depth increased
      depending on application time. S-MP and O-MP depths did not differ significantly.
      The invasion depths of the C-MP significantly increased compared with those in
      the O-MP. These results suggest that C-MP had a high tissue fixation rate.

PMID- 30282852
TI  - Skin Sensitization to Fluorescein Isothiocyanate Is Enhanced by Butyl Paraben in
      a Mouse Model.
AB  - Contact hypersensitivity (CHS) to preservatives is receiving increased attention.
      Parabens are widely used in foods, pharmaceutics and cosmetics as preservatives.
      The skin sensitizing activity of parabens remains controversial but a few
      investigations have been made as to whether parabens could facilitate
      sensitization to other chemicals. We have shown that di-n-butyl phthalate (DBP),
      a phthalate ester, has an adjuvant effect in a fluorescein isothiocyanate (FITC)
      induced CHS mouse model. We have also demonstrated that DBP activates transient
      receptor potential ankyrin 1 (TRPA1) cation channels expressed on sensory
      neurons. Comparative studies of phthalate esters revealed that TRPA1 agonistic
      activity and the adjuvant effect on FITC-CHS coincide. Here we focused on two
      commonly used parabens, butyl paraben (BP) and ethyl paraben (EP), as to their
      adjuvant effects. BALB/c mice were epicutneously sensitized with FITC in acetone
      in the presence or absence of a paraben. Sensitization to FITC was evaluated as
      the ear-swelling response after FITC challenge. BP but not EP enhanced skin
      sensitization to FITC, but the effect of BP was much weaker than that of DBP.
      Mechanistically, BP enhanced the trafficking of FITC-presenting CD11c+ dendritic
      cells (DCs) from the skin to draining lymph nodes as well as cytokine production
      by draining lymph nodes. When the TRPA1 agonistic activity was measured with a
      cell line expressing TRPA1, BP exhibited higher activity than EP. The present
      study provides direct in vivo evidence that BP causes sensitization to other
      chemicals by means of a mouse FITC-CHS model.

PMID- 30282853
TI  - Recent  decreasing  trends  of  exposure  to  PCDDs/PCDFs/dioxin-like  PCBs  in 
      general  populations,  and  associations with  diabetes,  metabolic  syndrome, 
      and  gout/hyperuricemia.
AB  - The author reviewed recent reports about the blood levels and dietary intake of
      polychlorinated dibenzo-p-dioxins (PCDDs)/furans (PCDFs)/dioxin-like
      polychlorinated biphenyls (DL-PCBs) to investigate the trends of dioxin exposure,
      and epidemiologic studies on the associations of blood levels of dioxins with
      metabolic diseases. In recent years, dietary intake of dioxins has been
      decreasing, and the means are equal to or less than 1.0 pg Toxic Equivalents
      (TEQ)/kg/day in the general populations of several countries. The blood levels of
      dioxins are also decreasing, probably because of reduced dietary intake. Many
      cross-sectional studies reported positive associations between blood levels of
      some isomers or TEQ-based concentrations of PCDDs/PCDFs/DL-PCBs and diabetes in
      general populations. Three cohort studies on populations with heavy exposure and
      two nested case-control studies on general populations have also been published,
      but the results are inconsistent. Three large-scale cross-sectional studies and
      two cohort studies reported an association between blood levels of some isomers
      or TEQ-based concentrations of PCDDs/PCDFs/DL-PCBs and metabolic syndrome. In
      addition, three cross-sectional studies reported significant positive
      associations with gout/hyperuricemia. Further prospective studies and
      experimental studies are needed to establish cause-effect relationships, and to
      clarify the biological mechanisms for the association between background exposure
      to dioxins and potential health effects. J. Med. Invest. 65:151-161, August,
      2018.

PMID- 30282854
TI  - Understanding metabolic conversions and molecular actions of flavonoids in
      vivo:toward new strategies for effective utilization of natural polyphenols in
      human health.
AB  - Many papers have suggested the health-beneficial activity of natural dietary
      polyphenols to prevent chronic diseases and aging processes in humans. It is
      generally recognized that polyphenols are absorbed from the intestines and
      metabolized into the phase-II conjugates, i.e., the glucuronides and sulfates.
      For example, a major dietary flavonoid, quercetin, abundant in onion and
      buckwheat, is metabolized after oral intake into its conjugates, such as
      quercetin-3-O-glucuronide and quercetin-3'-O-sulfate, whereas no aglycone was
      found in the human plasma. Therefore, to understand the mechanisms of the
      biological activity of quercetin in vivo, we should focus on the molecular
      actions of these conjugates. In the last decade, we have demonstrated the unique
      actions of quercetin-3-O-glucuronide at sites of inflammation, including specific
      accumulation in macrophages and the following deconjugation into active aglycone,
      catalyzed by the macrophage-derived beta-glucuronidase. This review summarizes
      recent findings regarding the anti-inflammatory mechanisms of quercetin
      conjugates in macrophages and propose a possible strategy for the effective
      utilization of natural polyphenols in our daily diet for prevention of age
      related chronic diseases. J. Med. Invest. 65:162-165, August, 2018.

PMID- 30282855
TI  - Effect of Janus kinase inhibition by tofacitinib on body composition and glucose
      metabolism.
AB  - Tofacitinib is the first Janus Kinase (JAK) inhibitor to treat moderately to
      severely active RA. In this study, we investigated whether the effect of
      tofacitinib have any effects on body composition in mice and female patients with
      RA. Female C57BL/6 mice fed with a high-fat diet were treated with 30 mg/kg/day
      tofacitinib or vehicle for 70 days. Following treatment, trunk muscle,
      subcutaneous fat, and visceral fats were measured using X-ray computed tomography
      CT scan. Glucose tolerance and insulin sensitivity were assessed. In female RA
      patients treated with biological disease modified anti-rheumatic-drugs
      (biological DMARDs) or tofacitinib (n=4 per group), we also evaluated the body
      composition after 3 months from the start of treatment initiation using
      bioelectrical impedance analysis. Treatment with tofacitinib did not affect the
      body weight, and body composition in C57BL/6 mice. It also did not affect
      glucose, and insulin tolerance in mice. In patients with RA, treatment with
      biological DMARDs did not affect the body composition whereas the muscle mass was
      unchanged after receiving tofacitinib and the fat mass was significantly
      increased. J. Med. Invest. 65:166-170, August, 2018.

PMID- 30282856
TI  - UVA-LED device to disinfect hydroponic nutrient solution.
AB  - The number of plant factories in which crops are cultivated in an artificial
      environment has been increasing every year. In cultivation techniques involving
      hydroponics, plants are supplied with a circulating nutrient solution, which can
      become contaminated by pathogens that can propagate and spread throughout plant
      factories. Therefore, strategies to disinfect hydroponic nutrient solutions are
      needed. In this study, we developed a new disinfection device equipped with an
      ultraviolet A (UVA) light emitting diode (LED) that can be used to disinfect
      hydroponic nutrient solutions in plant factories. We first evaluated the basic
      disinfection capability of the device and then estimated its bactericidal effect
      in a small scale model system. The log survival ratio was related to UVA
      irradiation fluence and the volume of nutrient solution. From the assay results,
      we devised a kinetics equation to describe the relationship between nutrient
      solution volume, log survival ratio, and UVA fluence. Together our results show
      that UVA irradiation could be used to disinfect hydroponic nutrient solutions,
      and the derived kinetics equations can be used to determine optimal conditions,
      such as nutrient solution volume, UVA irradiation, and killing activity, to
      develop devices that disinfect hydroponic nutrient solutions. J. Med. Invest.
      65:171-176, August, 2018.

PMID- 30282857
TI  - Physical features of pediatric patients with lumbar spondylolysis and
      effectiveness of rehabilitation.
AB  - The purpose of this study was to evaluate the physical features of pediatric
      patients with lumbar spondylolysis (LS), factors that increase the load during
      compensatory movements at the lumbar spine, and the outcomes of rehabilitation.
      Twenty patients were included. Fifteen items were used:fingertip-to-floor
      distance (FFD), straight leg raising (SLR), heel-to-buttock distance (HBD),
      tightness of the rectus femoris, the lateral and medial rotator muscles,
      iliopsoas, tensor fascia lata, adductor muscles, soleus muscle, and latissimus
      dorsi, and trunk rotation, sit-ups and endurance of the abdominal and back
      muscles. Initial findings were judged as positive or negative using previously
      reported cut-off values and were re-evaluated 2 or 3 months later. Positive tests
      were found for HBD and tightness of the rectus femoris in 85% of the patients,
      for endurance of the abdominal muscles in 75%, SLR and sit-ups in 70%, and FFD
      and tightness of the external rotator muscles in 60%. The physical features
      varied according to the type of sport played, and some patients were refractory
      to rehabilitation. Only 17.6%, 33.3%, and 40.0% of patients with initially
      positive findings for HBD, tightness of the external rotator muscles, and
      endurance of the abdominal muscles, respectively, achieved improvements after
      rehabilitation. J. Med. Invest. 65:177-183, August, 2018.

PMID- 30282858
TI  - Impact of the use of Kampo medicine in patients with esophageal cancer during
      chemotherapy:a clinical trial for oral hygiene and oral condition.
AB  - OBJECTIVE: The aim of this study was to investigate the impact of the use of two
      Kampo medicines on oral mucositis, tongue coating bacteria, and gingiva condition
      in patients with esophageal cancer undergoing chemotherapy. METHODS: Twenty-three
      esophageal cancer patients who receive chemotherapy at Tokushima University
      Hospital, were included. The participants, who received professional oral
      healthcare, were randomly divided into three groups:7 subjects received
      Daiokanzoto sherbets, 7 subjects received Hangeshashinto sherbets, and 9 subjects
      received nothing (control). The numbers of total bacteria and specific
      periodontopathogenic bacteria in tongue coating were determined in addition to
      clinical parameters. RESULTS: No difference on the onset of oral mucositis was
      found among the three groups. However, tongue coating index, gingival index (GI),
      plaque index, the number of total bacteria, Fusobacterium nucleatum and
      Campylobacter rectus were decreased during chemotherapy. More specifically, GI as
      well as the number of F. nucleatum and C. rectus were decreased significantly in
      the Daiokanzoto group when compared to the control group (psize 8 < 0.05). No
      such differences were observed for the group receiving Hangeshashinto.
      CONCLUSION: This clinical trial showed that Daiokanzoto might be effective in
      attenuating gingival inflammation and reducing the levels of periodontopathogenic
      bacteria in patients with esophageal cancer. J. Med. Invest. 65:184-190, August,
      2018.

PMID- 30282859
TI  - Definition of Prognosis Based on Lymph Node Metastasis and Elevation of Serum C
      Reactive Protein for Patients with Gastric Carcinoma Treated with Curative
      Resection.
AB  - PURPOSE: The aim of this study was to develop prognostic criteria based on the
      combination of nodal metastasis and preoperative elevation of serum C-reactive
      protein (CRP) for patients with gastric carcinoma that have been treated with
      curative resection. METHODS: Three hundred and twenty patients with gastric
      carcinoma who had been treated with curative resection were enrolled. One point
      was provided for each incidence of nodal metastasis and preoperative elevation of
      serum CRP and we examined whether this cumulative score system could provide a
      strict stratification of survival. RESULTS: Significant differences regarding
      survival were observed both between patients with scores of 0 and 1 (P < 0.0001)
      and between patients with scores of 1 and 2 (P < 0.0001). Multivariate analysis
      showed that the cumulative score (P = 0.0003) and the depth of the tumor (P =
      0.016) were independent prognostic indicators. CONCLUSIONS: Criteria for the
      prediction of prognosis in gastric carcinoma treated with curative resection
      based on tumor-related and host-related factors could provide a strict
      stratification. J. Med. Invest. 65:191-194, August, 2018.

PMID- 30282860
TI  - Novel formula using triceps skinfold thickness to revise the Cockcroft-Gault
      equation for estimating renal function in Japanese bedridden elderly patients.
AB  - In recumbent elderly patients, creatinine clearance (eCCr) estimated by the
      Cockcroft-Gault (CG) equation may not necessarily reflect renal function. We
      aimed to develop a novel formula to revise the CG equation using anthropometric
      measurements in bedridden elderly patients and evaluate its clinical utility. The
      subjects included 77 bedridden Japanese patients aged ? 65, hospitalized at
      Naruto Yamakami Hospital. The actual CCr (mCCr) value was measured using the 24
      hour urine collection method. Anthropometric data, such as skeletal muscle mass,
      body fat mass (BFM), and triceps skinfold thickness (TSF), were collected. We
      established a novel formula to estimate CCr(BFM) or CCr(TSF) by correcting the
      eCCr(Enz+0.2) value with BFM or TSF. The stage of classification of renal
      dysfunctions in patients with eGFR(BFM) or eGFR(TSF) was equivalent to the
      GFR(control) based on the mCCr. Notably, the novel equation for eCCr based on TSF
      (eCCr(TSF)), dubbed the "Naruto" formula, can be useful to evaluate renal
      function in bedridden elderly patients without expensive equipment or additional
      costs. In this study, mCCr was considered to be the true renal function of the
      patient, but whether and to what extent mCCr correlates with inulin clearance is
      unknown. J. Med. Invest. 65:195-202, August, 2018.

PMID- 30282861
TI  - Investigation  of  dose-dependent  effects  of  fat  on  blood glucose,  serum 
      insulin,  and  appetite  sensation.
AB  - Humans have a high preference for fat, and its excessive intake leads to obesity.
      This study aimed to investigate the effects of dose-dependent fat intake on
      biological responses and postprandial appetite sensation in healthy adult
      subjects. Age and body mass index were 29 +/- 1 years and 21.1 +/- 0.4 kg/m2,
      respectively. We conducted a randomized, crossover trial and measured laboratory
      data and appetite sensation via the visual analog scale. Each participant was
      provided with four different test meals. They consisted of common, basic foods
      and contained 75 g liquid glucose and 4 slices of crackers to which 0 g butter
      (control), 10 g butter (B10), 20 g butter (B20), and 40 g butter (B40) were
      added, respectively. The results indicated that single ingestion of butter did
      not influence laboratory values of glucose, insulin, glucose-dependent
      insulinotropic polypeptide (GIP), total bile acids, or high-sensitivity CRP (hs
      CRP). Regarding postprandial appetite sensation, appetite ratings for fullness
      were the highest after the B40 meal (p < 0.05);however, satisfaction ratings were
      not significantly different after the ingestion of this meal. Ratings were
      significantly different after the B20 meal. In conclusion, healthy adult subjects
      experienced fullness and satisfaction after ingesting 20-40 g of butter. J. Med.
      Invest. 65:203-207, August, 2018.

PMID- 30282862
TI  - Urinary Exosomal mRNA of WT1 as Diagnostic and Prognostic Biomarker for Diabetic
      Nephropathy.
AB  - Diabetic nephropathy (DN) is the major cause of end-stage renal failure and is
      associated with increased morbidity and mortality as compared to other causes of
      renal disease. Albuminuria is often the first clinical indicator of the presence
      of DN. However, albuminuria or proteinuria is a common symptom in patients with
      various renal disorders. Therefore, specific biomarkers for the diagnosis of DN
      are required. A primary hallmark of DN is the progressive damage and death of
      glomerular podocytes, resulting in the leaking of proteins into the urine.
      Urinary exosomes released by podocytes are microvesicles containing information
      of the originated cells. Podocyte-derived signal transduction factors (PDSTFs)
      are good candidates to assess podocyte injuries. The profile of PDSTFs in urinary
      exosomes from patients with DN is different from that from patients with minimal
      change nehrotic syndrome. In addition, PDSTFs molecules in exosomes were derived
      from primary murine podocytes under high glucose conditions. Among PDSTFs in
      urinary exosomes, Wilms tumor 1 (WT1) levels reflected damage of diabetic
      glomeruli in the patients. Urinary exosomal WT1 can predict the decline in eGFR
      for the following several years. In conclusion, urinary exosomal WT1 is a useful
      biomarker to improve risk stratification in patients with DN. J. Med. Invest.
      65:208-215, August, 2018.

PMID- 30282863
TI  - Effects of FM system fitted into normal hearing ear on speech-in-noise
      recognition in Japanese school-aged children with unilateral severe-to-profound
      hearing loss.
AB  - OBJECTIVES: We examined speech recognition ability of elementary school-aged
      Japanese children with unilateral hearing loss under noisy environments and then
      examined the effects of the FM system fitted into their normal hearing ear on
      their speech recognition ability. METHODS: Twelve children with severe-to
      profound sensorineural hearing loss and ten age-matched children with bilateral
      normal hearing received speech recognition test in quiet and noisy environments.
      Other nine children with severe-to-profound sensorineural hearing loss received
      speech recognition test with or without the FM receiver fitted to the normal
      hearing ear in quiet and noisy environments. RESULTS: Signal-to-noise ratio (SNR)
      in Japanese elementary school classrooms was estimated to be -6.9 dB at a
      preferential seat. In noisy environment of -5 dB SNR similar to working
      classrooms, the correct rates of speech recognition test in children with
      unilateral hearing loss were significantly lower, compared with those in children
      with bilateral normal hearing. In the noisy environment, the correct rates in
      children aided by the FM system with unilateral hearing loss were significantly
      better, compared with unaided ones. CONCLUSION: The results suggested that the FM
      system is recommended as an audiological management for improvement of speech
      recognition of children with unilateral hearing loss in noisy classrooms. J. Med.
      Invest. 65:216-220, August, 2018.

PMID- 30282864
TI  - Can systematic lymphadenectomy be omitted for low-risk endometrial cancer?
AB  - The objective of this study was to identify pathological indicators that could be
      used to identify a subgroup of patients with apparent stage I endometrial cancer
      who do require retroperitoneal lymphadenectomy. 188 T1 endometrial cancer
      patients underwent primary surgery at Tokushima University Hospital. We
      retrospectively evaluated their clinical records and histopathological factors.
      Systematic lymphadenectomy was performed for 149 patients, and 39 patients (grade
      1 with < 5 mm of myometrial invasion) were treated without lymphadenectomy. Lymph
      node metastases were found in 19 (12.8%) of the lymphadenectomy cases. Twenty
      four patients with a T1a endometrium-limited lesion did not exhibit lymph node
      metastasis. Three (3.1%) of the 95 patients with a T1a lesion exhibited lymph
      node metastasis, and these 3 cases exhibited approximately 50% myometrial
      invasion. The 39 low-risk patients who did not undergo systematic lymphadenectomy
      remain alive without recurrence. Systematic lymphadenectomy could be omitted for
      patients with a grade 1 tumor and minor myometrial invasion of less than 5mm. J.
      Med. Invest. 65:221-224, August, 2018.

PMID- 30282865
TI  - Methanol extraction fraction from Citrus Sudachi peel exerts lipid reducing
      effects in cultured cells.
AB  - Ectopic fat accumulation is associated with insulin resistance and type 2
      diabetes mellitus. Citrus sudachi is an evergreen tree that is found mainly in
      Tokushima Prefecture in Japan. Previously, it was demonstrated that Citrus
      sudachi could inhibit the rising trend of blood glucose and fatty acid in human
      subjects. In the current study, we illustrated the function of methanol extracts
      from sudachi peel and investigated the mechanism of this effect. We got the five
      kinds of methanol extracts by using diaion HP-20, and those were named by
      hydrophobicity from M-F1 to M-F5. Among the 5 kinds of sudachi methanol extracts,
      only M-F4 significantly decreased the intracellular triglyceride of C2C12 cells.
      It augmented the AMPK activity and increased the transcription of PPARalpha and
      its downstream targets CPT-1b and UCP2. In conclusion, M-F4 improved the lipid
      metabolism possibly through AMPK, PPARalpha and their downstream targets like CPT
      1b and UCP2. Furthermore, this extract may be useful for preventing obesity and
      diabetes related diseases. J. Med. Invest. 65:225-230, August, 2018.

PMID- 30282866
TI  - Assessment of renal function in Japanese children with malignancies using serum
      cystatin C.
AB  - Several factors besides renal function influence serum cystatin C (CysC) levels.
      The present study evaluates the value of serum CysC and the equation for CysC
      based estimated glomerular filtration rate (CysC-eGFR) for Japanese children with
      malignancies. We collected information at 36 time points from 13 patients aged <=
      17 years with malignancies. We assessed tumor activity, cell recovery phase after
      chemotherapy, neutropenia phase, inflammation response and medication with
      granulocyte-colony stimulating factor, steroid, and levothyroxine as risk factors
      associated with serum CysC levels. Although no 24-h creatinine clearance (CCr)
      data collected at 36 time points indicated renal dysfunction, serum CysC levels
      were above and below the reference values at four and five time points,
      respectively. The frequency of elevated serum CysC levels was higher in patients
      without therapy or with stable or progressive disease than among those with a
      complete or partial response (p = 0.0046). The correlation coefficient between
      CCr and CysC-eGFR was 0.355 (p = 0.054), but this improved to 0.663 (p = 0.0010)
      when restricted to patients with a complete or partial response. Levels of serum
      CysC might become elevated regardless of renal function, and CysC-eGFR might
      become unpredictable during the active phase of tumors. J. Med. Invest. 65:231
      235, August, 2018.

PMID- 30282868
TI  - Effect of wild grape on the signaling of histamine H1 receptor gene expression
      responsible for the pathogenesis of allergic rhinitis.
AB  - As expression level of allergic disease-sensitive genes are correlated with
      allergic symptom severity, suppression of these gene expressions could be good
      therapeutics. We have demonstrated that PKCdelta signaling and NFAT signaling,
      involve in histamine H1 receptor (H1R) and IL-9 gene expressions, respectively,
      are responsible for the pathogenesis of allergic rhinitis. We explore anti
      allergic compounds that suppress these signaling pathways and found that wild
      grape (WG) contains such compounds. Here, we investigated the effect of WG hot
      water extract (WGE) on the signaling pathways for PKCdelta-mediated H1R and NFAT
      mediated IL-9 gene expressions. WGE suppressed histamine/PMA-induced H1R gene up
      regulation in HeLa cells. Toluene-2,4-diisocyanate (TDI)-induced H1R mRNA
      elevation in TDI-sensitized rats was also suppressed by WGE treatment. Treatment
      with WGE in combination with Awa-tea, suppresses NFAT signaling-mediated IL-9
      gene, markedly alleviated nasal symptoms. Furthermore, WGE suppressed PMA-induced
      IL-33 gene up-regulation in Swiss 3T3 cells. Data suggest that combination of
      WGE, suppresses PKCdelta signaling with Awa-tea, suppresses NFAT signaling would
      have distinct clinical and therapeutic advantages as a substitute for anti
      allergic drugs. In addition, as the expression level of IL-33 mRNA was correlated
      with the blood eosinophils number in patients with pollinosis, WG could alleviate
      eosinophilic inflammation through the suppression of IL-33 gene expression. J.
      Med. Invest. 65:242-250, August, 2018.

PMID- 30282867
TI  - Association of short-term ozone exposure with pulmonary function and respiratory
      symptoms in schoolchildren:A panel study in a western Japanese city.
AB  - The average annual ozone levels have been increasing in Japan, even though the
      high ozone levels have decreased in recent years. There is limited information on
      the relationship between ozone exposure, pulmonary function, and respiratory
      symptoms in schoolchildren in Japan. The aim of this study was to investigate the
      effects of short-term ozone exposure on pulmonary function and respiratory
      symptoms in Japanese schoolchildren. Afternoon peak expiratory flow (PEF) values
      and respiratory symptom scores were recorded daily in 276 schoolchildren from
      September to October 2016 and from January to February 2017. The association of
      daily ozone levels with PEF was assessed using a linear mixed model and that with
      respiratory symptoms was evaluated by generalized estimating equations logistic
      regression analysis. There was a significant association of daily ozone levels
      with PEF values. A 13.6-ppb increment in the interquartile range for ozone
      exposure was significantly associated with a decrease in PEF of -3.67 L/min (95%
      confidence interval -4.73, -2.61). However, increased ozone levels were not
      associated with an increased risk of respiratory symptoms. Our present findings
      suggest that more attention should be paid to the potential adverse effects of
      short-term ozone exposure on pulmonary function in schoolchildren. J. Med.
      Invest. 65:236-241, August, 2018.

PMID- 30282869
TI  - Clinical characteristics of dermatomyosits/polymyositis associated interstitial
      lung disease according to the autoantibody.
AB  - BACKGROUND: Dermatomyositis (DM) and polymyositis (PM) often have association
      with interstitial lung disease (ILD) which have disease specific autoantibody.
      METHODOLOGY: We reviewed medical records of DM/PM associated ILD from January
      2000 to December 2017 according to the autoantibody. RESULT: We identified 52
      patients, of whom 30 were antibody negative, 18 had anti aminoacyl-tRNA
      synthetases (ARS) antibodies and 4 had anti melanoma differentiation-associated
      gene (MDA)-5 antibody. In high resolution computed tomography (HRCT) of the
      chest, area of ground glass opacity (GGO), consolidation, and lung tip
      consolidation were more extensive in anti MDA-5 antibody positive patients
      (p=0.051, p=0.026, and p=0.027, respectively). Among laboratory findings, GOT had
      strong correlations with CPK (r=0.889, p < 0.001), and LDH (r=0.910, p < 0.001).
      Among roentgenographic findings, there were moderate correlations between GGO and
      consolidation (r=0.668, p < 0.001), and between reticular shadow and traction
      bronchiectasis (p=0.633, p < 0.001). ILD patients with anti MDA-5 antibodies had
      decreased survival (1.00 vs 84.3, 22.9 months, p < 0.001). CONCLUSION: ILD
      patients with anti ARS antibody had intense inflammation, but reversible fibrosis
      and good prognosis. On the other hand, anti MDA-5 antibody positive ILD patients
      had shorter survival. Extent of parenchymal shadow and serum GOT were useful
      indicator of disease activity of PM/DM associated ILD patients in our cohort. J.
      Med. Invest. 65:251-257, August, 2018.

PMID- 30282870
TI  - Human airway trypsin-like protease (HAT) is released into saliva.
AB  - We first discovered human airway trypsin-like protease (HAT) in human mucoid
      sputum. Precursor HAT (47 kDa), a cell surface type II transmembrane serine
      protease, is proteolyzed to mature HAT (27 kDa). Hitherto, HAT has not been
      detected in other biological fluids except for human sputum. We aimed to clarify
      whether human saliva contains mature HAT. Trypsin-like protease was isolated from
      saliva of healthy volunteers by a method adopted for isolation of HAT from sputum
      using Boc-Phe-Ser-Arg-MCA as the substrate. Biochemical properties of purified
      protease were similar to those of recombinant HAT (rHAT). HAT concentration in
      saliva was measured by ELISA, and immunoreactive HAT:total protein ratio (ng/mg)
      in saliva samples from healthy subjects was similar to that in mucoid sputum. RT
      PCR showed that HAT mRNA was expressed in human gingival epithelial cells but not
      in gingival fibroblasts. Both indirect immunofluorescence and western blotting
      using monoclonal antibody for alpha-smooth muscle actin (alpha-SMA;a
      myofibroblast marker) showed that HAT enhanced alpha-SMA fiber expression in
      gingival fibroblasts. These results indicate that both mucoid sputum and saliva
      from healthy subjects have similar concentrations of mature HAT, and HAT is
      related to certain physiological functions and pathological states of
      myofibroblasts in the oral cavity. J. Med. Invest. 65:258-267, August, 2018.

PMID- 30282871
TI  - The experiences of husbands present at their wives' emergency cesarean sections.
AB  - The aim of this study was to clarify the experiences of husbands present at their
      wives' emergency cesarean sections. Semi-structured interviews were conducted for
      nine husbands who attended their wives' emergency cesarean sections. The results
      were analyzed using a qualitative inductive approach. Several categories such as
      [wife's labor pain will be unbearable if I look], [situation was beyond one's
      control], and [sense of relief experienced by midwife care] were extracted from
      the husbands' experiences the need for an emergency cesarean section was
      established. Additional categories such as [sense of relief at cesarean section
      decision], [convincing oneself], and [anxiety for life and hope for safety] were
      extracted at the time of the emergency cesarean section decision. Other
      categories [anxiety while waiting for prolonged periods], [ease of mind with
      family], and [pleasure in meeting the baby] were extracted from the husbands'
      experiences while waiting for their wives' cesarean section. Finally, the
      categories of [unloading of responsibilities], [to thank my wife], and [remaining
      anxious and fearful] were extracted from the husbands' experiences on their wives
      return to their hospital rooms. Husbands were anxious about the life and safety
      of their wife and child, and considered their futures in case of an unexpected
      occurrence. J. Med. Invest. 65:268-273, August, 2018.

PMID- 30282872
TI  - Age-dependent texture features in skeletal muscle ultrasonography.
AB  - Texture analysis characterizes regions in an image by their texture content and
      has been utilized to infer the underlying structures of medical images such as
      skeletal muscles. Although potentially useful in tissue diagnosis and assessing
      disease progression of neuromuscular diseases, the use of texture analysis in
      such purposes are limited, due to lack of information such as effects of aging.
      Thus, we performed texture analysis of medial gastrocnemius in healthy
      individuals form their 20s to late 80s. Among the 283 texture features in 6
      classes, the features related to histogram, co-occurrence matrix, absolute
      gradient, and wavelet were correlated to age in 17-40% of the parameters, while
      none of the features related to run-length matrix and autoregressive model had
      significant correlation to age. This study showed that age-dependency in many
      texture features are present and need to be taken into account in elucidating the
      clinical significance. By contrast, the features related to run-length matrix and
      autoregressive model could have clinical utility. J. Med. Invest. 65:274-279,
      August, 2018.

PMID- 30282873
TI  - Attachment Disorder and Early Media Exposure: Neurobehavioral symptoms mimicking
      autism spectrum disorder.
AB  - Many studies have reported many adverse effects of children's use of media. These
      effects include reduced cognitive development and hyperactivity and attention
      disorders. Although it has been recommended that child be kept away from the
      media during the early developmental period, many modern parents use the media as
      a way to calm their children. Consequently, these children lack the opportunity
      to form selective attachments by reduced social engagement. These children's
      symptoms occasionally mimic autism spectrum disorder (ASD). However, few studies
      have examined the symptoms children develop with early media exposure. Here, we
      present a boy exposed to the media during his early development who was diagnosed
      with attachment disorder. He was unable to make eye contact and was hyperactive
      and had delayed language development, like children with ASD. His symptoms
      improved dramatically after he was prevented from using all media and encouraged
      to play in other ways. After this treatment, he would make eye contact, and
      talked about playing with their parents. Simply avoiding the media and playing
      with others can change the behavior of a child with ASD-like symptoms. It is
      important to understand the symptoms caused by attachment disorder and early
      media exposure. J. Med. Invest. 65:280-282, August, 2018.

PMID- 30282874
TI  - A case of solitary paraaortic lymph node recurrence of lung squamous cell
      carcinoma after resection.
AB  - Solitary abdominal paraaortic lymph node recurrence after radical lung cancer
      surgery is very rare. Here, we report a case of a solitary abdominal paraaortic
      lymph node recurrence of lung squamous cell carcinoma (SCC). A 63-year-old man
      was diagnosed with lung SCC (cT1cN0M0 stage IA3), underwent a video-assisted
      right lower lobectomy (ND2a-1), and the pathological findings showed SCC
      (pT1cN0M0 stage IA3). The EGFR mutation and ALK translocation statuses of SCC
      were negative, and adjuvant therapy was not performed. Follow-up positron
      emission tomography - computed tomography (PET/CT) showed a solitary
      fluorodeoxyglucose (FDG)-concentrated region in the swollen paraaortic lymph
      node. A paraaortic lymph node biopsy was performed by open laparotomy, to
      determine the precise diagnosis and identify the genetic status. Pathological
      findings revealed that the paraaortic lymph node contained poorly differentiated
      SCC, which was thought to metastasize from the lung cancer. The genetic status of
      the lymph node recurrence revealed a lack of EGFR mutations, ALK translocations,
      and ROS1 mutations, while the tumor proportion score (TPS) of PD-L1 was 55%, and
      we therefore administered pembrolizumab, an immune checkpoint inhibitor. Biopsies
      are very important for achieving precise diagnoses and determining the genetic
      statuses of tumors, since molecular-targeting drugs and immune checkpoint
      inhibitors are available. J. Med. Invest. 65:283-285, August, 2018.

PMID- 30282875
TI  - Convulsive seizure and pulmonary edema during hyperbaric oxygen therapy:A case
      report.
AB  - Hyperbaric oxygen therapy (HBOT) for carbon monoxide (CO) poisoning is widely
      performed to prevent delayed neuropsychiatric syndrome. Although HBOT can
      generally be performed with safety, the appropriate management of HBOT still
      remains unestablished. A 31-year-old man was transferred to our facility to
      undergo HBOT in a multiplace chamber with a diagnosis of CO poisoning. The first
      HBOT session ended uneventfully. During the second HBOT session, the patient
      suddenly experienced convulsive seizures. The accompanying doctor administered
      intravenous propofol to stop the convulsion and terminated the HBOT. Soon after
      the convulsion, the patient developed frothy secretions through the endotracheal
      tube with impaired oxygenation. Head computed tomography scan showed no
      abnormalities, suggesting the seizure was associated with complications of HBOT.
      A chest X-ray revealed bilateral pulmonary edema, and echocardiography revealed
      normal cardiac function, indicating that the pulmonary edema resulted from HBOT
      or neurogenic mechanism secondary to the seizure. The patient's respiratory
      status improved without recurrence of the seizure and no delayed neurological
      sequelae was seen afterwards. Here we report unexpected rare adverse events
      during HBOT. Hyperbaric oxygen therapy for acute indications should be performed
      in multiplace chambers, with appropriate preparation and medical equipment. J.
      Med. Invest. 65:286-288, August, 2018.

PMID- 30282876
TI  - A  case  of  adenoid  cystic  carcinoma  of  the  breast.
AB  - An 85-year old woman who had a large tumor in the left breast came to our out
      patient clinic. Computed tomography showed multiple lung tumors in addition to a
      huge tumor in the left breast. A needle biopsy brought about a histological
      diagnosis of ductal carcinoma. A simple mastectomy was performed and a
      histological examination using the resected specimen demonstrated a coexistence
      of an adenoid structure and a false ductal structure according the histologic
      characteristics of adenoid cystic carcinoma, which is quite rare among breast
      tumors. J. Med. Invest. 65:289-291, August, 2018.

PMID- 30282877
TI  - Manifestation of intraoperative anaphylactic shock along with latex allergy:a
      pediatric case report.
AB  - Natural rubber latex (NRL) allergy is one of the most important causes of severe
      anaphylaxis during medical intervention. We report a pediatric case of latex
      allergy with multiple surgical histories. A 12-year-old girl developed
      anaphylactic shock during the pyeloplasty for ureteropelvic junction restenosis.
      Latex gloves or medications used during the surgery were suspected to be the
      cause of anaphylactic shock. We diagnosed her latex allergy on the basis of the
      results that serum latex-specific IgE, skin prick tests of extract from NRL
      gloves and recombinant Hev b 6.02 solution were positive. Basophil activation
      test of NRL gloves was also positive, supporting the diagnosis of immediate
      allergic reactions caused by NRL. It was speculated that a history of multiple
      surgeries in infancy became a trigger of sensitization to latex in this patient.
      Reoperation after the diagnosis of NRL allergy was carried out in a latex-free
      environment and completed without any allergic symptoms. It would be necessary to
      perform the pre-screening of latex allergy to prevent the onset of latex allergy
      especially in the patients with multiple surgical histories. J. Med. Invest.
      65:292-295, August, 2018.

PMID- 30282878
TI  - Retrosternal salvage reconstruction of esophageal discontinuity for a necrotic
      gastric tube after esophagectomy: A novel procedure.
AB  - In patients with esophageal cancer, esophageal conduit necrosis is a catastrophic
      complication of esophagectomy that requires surgical restoration. Because such
      patients are generally fatigued, less-invasive surgery is encouraged whenever
      possible. Therefore, we trim the sternum minimally above the healthy part of the
      gastric conduit, expose its surface, and then make anastomoses between the
      remnant esophagus and the exposed gastric conduit using a free jejunal graft
      through a retrosternal-subcutaneous route. The risk involved with this procedure
      is low, because we avoid manipulation of the heavily inflamed lesion due to
      mediastinitis. J. Med. Invest. 65:296-298, August, 2018.

PMID- 30282879
TI  - In Vitro and In Vivo Detection of Drug-induced Apoptosis Using Annexin V
      conjugated Ultrasmall Superparamagnetic Iron Oxide (USPIO): A Pilot Study.
AB  - PURPOSE: To investigate the binding potential of newly developed Annexin V
      conjugated ultrasmall superparamagnetic iron oxide (V-USPIO) for detection of
      drug-induced apoptosis in vitro and in vivo. METHODS: Apoptotic cells induced by
      camptothecin were incubated with or without Annexin V-USPIO at a concentration of
      0.089 mmol Fe/L in vitro. T2 values of the two cell suspensions were measured by
      0.47T nuclear magnetic resonance (NMR) spectrometer. Tumor-bearing mice were
      subjected to 1.5T MR scanner at 2 h after intraperitoneal injection of etoposide
      and cyclophosphamide. Following the pre-contrast T1- and T2-weighted imaging (0
      h), the post-contrast scan was performed at 2, 4, 6 and 24 h after intravenous
      injection of Annexin V-USPIO (100 MUmol Fe/kg). As a control, MRI was also
      obtained at 4 h after injection of USPIO without Annexin V. The ratio of tumor
      signal intensity (SI) on post-MRI for that on pre-MRI (Post/Pre-SI ratio) was
      calculated. After scanning, tumors were resected for pathological analysis to
      evaluate the distribution of iron and apoptotic cells. RESULTS: The suspension of
      apoptotic cells incubated with Annexin V-USPIO showed shorter T2 value than that
      without it. On T1-weighted imaging post/pre-SI ratio at 4 h after injection of
      Annexin V-USPIO showed 1.46, while after injection of USPIO without Annexin V was
      1.17. The similar distribution of iron and apoptotic cells was observed in
      concordance with high signal intensity area on post-T1-weighted imaging.
      CONCLUSION: A newly developed Annexin V-USPIO could have the potential for
      detection of drug-induced apoptosis.

PMID- 30282880
TI  - PD-L1 Expression in Non-Small-Cell Lung Cancer Including Various Adenocarcinoma
      Subtypes.
AB  - PURPOSE: Knowledge regarding programmed death-ligand 1 (PD-L1) expression in lung
      cancer is limited. We aim to clarify PD-L1-positive expression in non-small-cell
      lung cancer (NSCLC), including adenocarcinoma subtypes. METHODS: In all, 90 NSCLC
      specimens containing various adenocarcinoma subtypes, in addition to squamous
      cell carcinoma and large-cell carcinoma were selected. PD-L1 was
      immunohistochemically stained by murine monoclonal antibody clone 22C3. RESULTS:
      When PD-L1-positive expression was defined by tumor proportion score (TPS) >=1%,
      the positive cases were 0/11 in adenocarcinoma in situ, 0/12 in minimally
      invasive adenocarcinoma, 1/10 in lepidic predominant adenocarcinoma, 1/13 in
      papillary predominant adenocarcinoma, 8/14 in acinar predominant adenocarcinoma,
      6/11 in solid predominant adenocarcinoma, 0/3 in micropapillary predominant
      adenocarcinoma, 0/4 in invasive mucinous adenocarcinoma, 4/9 in squamous cell
      carcinoma, and 2/3 in large-cell carcinoma. PD-L1 positivity was higher in males,
      smokers, advanced pathologic stages, positive vessel invasion, and positive
      lymphatic invasion. Postoperative survival analysis revealed that PD-L1-positive
      expression was a significantly worse prognostic factor in univariate analysis for
      recurrence-free survival (RFS). CONCLUSION: PD-L1-positive tumors were frequent
      in acinar predominant adenocarcinoma and solid predominant adenocarcinoma than
      other adenocarcinoma subtypes. PD-L1 expression seemed to increase according to
      pathologic tumor progression, suggesting a worse postoperative prognosis in NSCLC
      patients.

PMID- 30282881
TI  - Correlations Between Serum Cholesterol and Vascular Lesions in Fabry Disease
      Patients.
AB  - BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder and shows
      globotriosylceramide (Gb3) accumulation in multiple organs, resulting from a
      deficiency of alpha-galactosidase. In patients with Fabry disease, cardiovascular
      disease occurs at an early age. Previous studies have shown that serum levels of
      high-density lipoprotein-cholesterol (HDL-C) increase in this disease, yet its
      clinical significance for cardiovascular disease remains unclear. Methods and
      Results: In order to determine why the serum HDL-cholesterol is high in various
      cardiovascular diseases of Fabry disease patients, we evaluated the serum lipid
      profiles, ocular vascular lesions, and levels of serum vascular endothelial
      growth factor (VEGF) and intercellular adhesion molecule-1 in 69 patients with
      Fabry disease diagnosed by genetic examination. The serum HDL-C/total cholesterol
      (T-Chol) ratio was significantly high, especially in male patients (41.5+/-1.7%)
      regardless of body mass index. Ocular vascular lesions were more likely to occur
      in female patients with a high HDL-C/T-Chol ratio compared with most male
      patients. Female patients with a high HDL-C/T-Chol ratio also presented a high
      serum VEGF level, suggesting that vascular endothelium dysfunction and
      arteriosclerotic changes progress more severely than in patients with a normal
      HDL-C/T-Chol ratio. In most patients, enzyme replacement therapy improved serum
      Gb3 and lyso-Gb3 levels, but these Gb3 and lyso-Gb3 still remained higher than in
      healthy controls, which appears to result in continuous vascular arteriosclerotic
      changes. CONCLUSIONS: We concluded that increased low-density lipoprotein
      cholesterol uptake to the vascular wall caused by endothelial dysfunction is
      likely to contribute to the high HDL-C/T-Chol ratio observed in Fabry disease
      patients.

PMID- 30282882
TI  - Positive Association of High Leptin Level and Abdominal Aortic Calcification in
      Men - The Prospective MINOS Study.
AB  - BACKGROUND: Severe abdominal aortic calcification (AAC) points to high
      cardiovascular risk and leptin stimulates arterial calcification; however,
      clinical data on their association are scarce. We studied the link between serum
      leptin and AAC severity and progression, and the effect of smoking and lipid
      levels, on this association in men. Methods and Results: At baseline, 548
      community-dwelling men aged 50-85 years underwent blood collection and lateral
      lumbar spine radiography. In 448 men, X-ray was repeated after 3 and 7.5 years.
      AAC was assessed using Kauppila's semiquantitative score. In multivariable
      models, high leptin was associated with higher odds of severe AAC (odds ratio
      [OR]=1.71 per SD, 95% confidence interval [CI]: 1.22-2.40). The odds of severe
      AAC were the highest in men who had elevated leptin levels and either were ever
      smokers (OR=9.22, 95% CI: 3.43-24.78) or had hypertriglyceridemia (vs. men
      without these characteristics). Higher leptin was associated with greater AAC
      progression (OR=1.34 per SD, 95% CI: 1.04-1.74). The risk of AAC progression was
      the highest in men who had elevated leptin levels and either were current smokers
      or had high low-density lipoprotein-cholesterol levels (OR=5.91, 95% CI: 2.46
      14.16 vs. men without these characteristics). These links remained significant
      after adjustment for baseline AAC and in subgroups defined according to smoking
      and low-density lipoprotein-cholesterol levels. CONCLUSIONS: In older men, high
      leptin levels are associated with greater severity and rapid progression of AAC
      independent of smoking, low-density lipoprotein-cholesterol or triglycerides.

PMID- 30282884
TI  - A rapid risk assessment of African swine fever introduction and spread in Japan
      based on expert opinions.
AB  - A rapid risk assessment was conducted using a questionnaire composed of 10
      questions asking experts in African swine fever (ASF) to identify and rank the
      potential risk factors associated with the introduction and spread of ASF in
      Japan. The experts participating in this risk assessment considered illegal food
      import, followed by transport routes and foreign workers, to be the most relevant
      pathway of ASF introduction into Japan. Kanto and Kyushu were identified as the
      most likely regions for ASF introduction. All experts agreed that China is the
      most likely source of ASF introduction into Japan. Most Japanese experts were of
      the view that the risk of ASF spread if introduced into Japan would be low, while
      foreign experts considered the risk to be moderate or high. Most experts answered
      that wild boars would play an important role in the persistence of ASF if the
      disease were to spread in Japan.

PMID- 30282883
TI  - How does Toxoplama gondii invade host cells?
AB  - Toxoplasma gondii is a highly prevalent protozoon that can infect all warm
      blooded animals, including humans. It is frequently used as an Apicomplexan
      parasite model in research. In this review, the invasion mechanism of T. gondii
      is described as a representative Apicomplexan parasite. The invasion machinery of
      T. gondii consists of the moving junction and the glideosome, which is a specific
      motor system for Apicomplexan parasites. I provide details about the moving
      junction, parasite-secreted proteins and host adhesion receptors, the glideosome,
      and calcium signaling, which generates the power for the gliding mobility of T.
      gondii. A detailed understanding of parasite invasion can be useful for the
      development of new effective drugs to inhibit this event and disrupt the
      Apicomplexan life cycle.

PMID- 30282885
TI  - ?

PMID- 30282886
TI  - ?

PMID- 30282887
TI  - Impact of the modification of the diagnostic criteria in the 2017 Bethesda System
      for Reporting Thyroid Cytopathology: a report of a single institution in Japan.
AB  - The Bethesda System for Reporting Thyroid Cytopathology has recently been revised
      in 2017 (TBSRTC 2017). This study aimed to evaluate the impact of modifying the
      diagnostic criteria in TBSRTC 2017 at a single institute. We retrospectively
      reviewed cytological specimens of 10,399 thyroid nodules submitted for thyroid
      fine-needle aspiration cytology. Among them, 56 atypia of undetermined
      significance or follicular lesion of undetermined significance (AUS/FLUS)
      nodules, 16 suspicious for malignancy (SFM) nodules, and 8 malignant nodules were
      re-categorized into follicular neoplasm or suspicious for a follicular neoplasm
      (FN/SFN). The incidence of FN/SFN was increased by 0.8%, while that of AUS/FLUS,
      SFM, and malignant nodule was decreased by 0.5%, 0.2%, and 0.1%, respectively. In
      nine (60%) of the 15 nodules that were re-classified from AUS/FLUS to FN/SFN
      nodules and re-aspiration was performed, it was possible to judge whether they
      were benign or malignant. Of the 24 patients with FN/SFN nodules originally
      diagnosed with SFM or malignant, 16 were followed up without surgical resection.
      In conclusion, TBSRTC 2017 only caused minor changes in the incidence of each
      diagnostic category. TBSRTC 2017 was revised to avoid false positives owing to
      noninvasive follicular thyroid neoplasm with papillary-like nuclear features
      (NIFTP) that account for >10% of papillary thyroid carcinomas; however, it is not
      necessary in low frequency NIFTP institutes or countries. In Japan, we propose
      active surveillance as an accepted option for clinically managing AUS/FLUS,
      FN/SFN, SFM, or malignant nodules having favorable benign clinical findings or
      being part of the low-risk group.

PMID- 30282888
TI  - Structure and function analysis of adiponectin receptors toward development of
      novel antidiabetic agents promoting healthy longevity.
AB  - Plasma adiponectin levels and expression of its receptors, AdipoRs are decreased
      in obesity, which cause insulin resistance and diabetes. AdipoR-deficient mice
      exhibit insulin resistance and impaired glucose tolerance. Moreover, newly
      identified AdipoR agonists not only improve insulin resistance but prolong
      lifespan shortened by obesity via AdipoR. Furthermore, efforts to promote
      structure-based drug discovery research at our laboratory have led to the first
      ever successful crystallization of AdipoR as well as to clarification of their
      structures. Structural analysis of AdipoRs as key molecules in lifestyle-related
      diseases is thus expected to lead not only to the acceleration of structure-based
      drug discovery but to the elucidation of novel aspects of the AdipoR structures
      and functions in the years to come. Finally, with the development of novel AdipoR
      targeted antidiabetic agents also capable of prolonging lifespan, the attainment
      of healthy longevity may finally be brought within reach.

PMID- 30282889
TI  - Plaque Stabilization by Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor
      in a Patient With Familial Hypercholesterolemia Undergoing Percutaneous Coronary
      Intervention.

PMID- 30282890
TI  - Reaching the unreached.

PMID- 30282891
TI  - Ultrasound and MRI Findings of Twin Pregnancies with Complete Hydatidiform Mole
      and Coexisting Normal Fetus: Two Case Reports.
AB  - BACKGROUND: Both twin pregnancies with complete hydatidiform mole and coexisting
      normal fetus (CHMCF) and partial hydatidiform mole can be found in association
      with a live fetus and a placenta displaying a molar degeneration. Two cases of
      CHMCF using magnetic resonance imaging (MRI) for a diagnosis are reported. CASE:
      In the first, CHMCF was suspected at 12 weeks of gestation. At 18 weeks of
      gestation, the existence of molar placenta and a sac separating from fetus and
      normal placenta was clearly depicted on MRI. At 19 weeks of gestations, she had
      termination of pregnancy because of a development of gestational trophoblastic
      neoplasia (GTN) and started chemotherapy. In the second case, CHMCF was suspected
      at 14 weeks of gestation. MRI demonstrated the existence of molar placenta and a
      sac separating from fetus and normal placenta. She chose induced abortion and
      there was no evidence of GTN during the 1 year-follow up period. Pathological
      examination in both cases was consistent with a complete hydration mole and a
      coexisting normal female fetus. CONCLUSION: MRI was useful for an accurate
      diagnosis for CHMCF.

PMID- 30282892
TI  - The Correlation Between Length of Work and Nasal Mucociliary Transport Time of
      Gas/Fuel Station Workers.
AB  - Gasoline contains toxic substances such as benzene, toluene, ethylbenzene, xylene
      (BTEX) that negatively influence gas/fuel station workers' health via continuous
      inhalation, causing loss of cilia and epithelial cell necrosis of the nasal
      mucosa. The aim of this study is to determine the correlation between length of
      work with nasal mucociliary transport time (NMCTT) of the gas/fuel station
      workers This study used a cross sectional design. The data were obtained from
      anamnesis, physical and NMCTT examinations of gas station workers in Yogyakarta,
      during November 2013. Inclusion criteria were: 1) 18-55 years old, 2) free of
      nasal topical medication for 10 days. Exclusion criterion: 1) acute rhinitis, 2)
      chronic sinusitis, 3) ever had nasal trauma, 4) ever had nasal surgery, 5)
      allergic rhinitis, and/or 6) septal deviation. Correlation analyses between
      length of work and NMCTT of gas station workers used Spearman correlation test
      with alpha 5% level of significance (p < 0.05). From 38 subjects, 27 (71.1%) were
      men and 11 (28.9%) women. Median length of work was 7.37 years, and NMCTT: 10.84
      +/- 5.60 minutes. Spearman's correlation test results between length of work and
      NMCTT showed (R): 0.578 (p = 0.001). Based on the results of this study, it can
      be concluded that there is a positive correlation between length of work with
      NMCTT of gas station workers.

PMID- 30282893
TI  - Associated Factors of Psychological Distress among Japanese NICU Nurses in
      Supporting Bereaved Families Who Have Lost Children.
AB  - PURPOSE: This study aimed (1) to examine the current status of psychological
      distress experienced by neonatal intensive care unit (NICU) nurses in supporting
      bereaved families, (2) to identify the factors associated with psychological
      distress, and (3) to understand the professional characteristics of nurses
      experiencing high psychological distress by comparing the study results with
      those of pediatricians. METHODS: We sent questionnaires to 64 NICUs. The
      psychological distress of nurses was classified into two groups based on the
      frequency of psychological distress experienced and analyzed using the chi2 test
      and Fisher's exact test. A multiple logistic regression analysis was used to
      investigate the factors related to psychological distress. RESULTS: Of the 384
      nurse respondents, 190 (49.5%) reported having supported bereaved families, 169
      of who were included in the analysis. A total of 123 nurses (72.8%) reported high
      levels of psychological distress. Our study revealed that the use of coping
      methods is associated with high psychological distress. The comparison with
      pediatricians revealed that nurses were significantly more likely to be female
      and had fewer years of working experience. Nurses were also significantly more
      likely to use coping methods and to experience high psychological distress.
      CONCLUSION: Clarifying the coping methods for psychological distress in
      supporting bereaved families may be necessary, and nurses need to identify
      appropriate coping methods. In nursing education, information on psychological
      distress related to children's deaths and bereavement care should be conveyed
      from the early stage and nurses must obtain preliminary knowledge. The creation
      of a bereavement follow-up system is recommended.

PMID- 30282894
TI  - Hyperbilirubinemia in Term Newborns Needing Phototherapy within 48 Hours after
      Birth in a Japanese Birth Center.
AB  - BACKGROUND: Hyperbilirubinemia in term newborns needing phototherapy within 48
      hours after birth, early-onset hyperbilirubinemia, has not been evaluated in
      recent Japanese healthy birth centers. In this study, we sought to determine the
      cause of early-onset hyperbilirubinemia in a Japanese healthy birth center and to
      evaluate the 1992 Kobe University phototherapy treatment criterion requiring
      total serum bilirubin (TSB) and unbound bilirubin (UB). METHODS: In this
      retrospective observational study, we collected data on newborns diagnosed with
      early-onset hyperbilirubinemia between 2009 and 2016 at the Chibune General
      Hospital. Causes of the disease were investigated, as well as which index (TSB or
      UB) was used for treatment decisions. RESULTS: Overall, 76 term newborns were
      included in the analysis. Twenty-seven newborns (36%) found the cause (ABO blood
      type incompatibility [n=17, 22%], polycythemia [n=8, 11%], and cephalohematoma
      [n=2, 3%]). However, 49 newborns (64%) did not find any causes (i.e., idiopathic
      hyperbilirubinemia). Of these, 27 observed more than 5% weight loss from birth
      weight. Seventy (92%) newborns had abnormal TSB only, and 5 (7%) had abnormal TSB
      and UB values. Only 1 (1%) newborn with only abnormal UB values received
      phototherapy. CONCLUSIONS: Altogether, data from this Japanese healthy birth
      center suggest that many apparently healthy newborns with or without excessive
      weight loss develop early-onset hyperbilirubinemia. In the 1992 Kobe University
      phototherapy treatment criterion, TSB, not UB, was the main index used to make
      treatment decisions in these patients.

PMID- 30282895
TI  - Exploring a Novel Screening Method for Patients with Oral Squamous Cell
      Carcinoma: A plasma Metabolomics Analysis.
AB  - AIM: This study aimed to explore novel metabolite biomarker candidates for
      screening oral squamous cell carcinoma (OSCC). PATIENTS & METHODS: We collected
      plasma samples from 48 patients with OSCC and 29 with an oral disease and
      conducted a plasma metabolomics analysis of patients with OSCC using gas
      chromatography mass spectrometry. Then, we used the cross-validation procedure to
      ensure the accuracy of biomarker candidates. RESULTS: We selected four biomarker
      candidates against OSCC. Their sensitivity was more than 90%, and the AUC was
      over 0.9 according to the receiver operating characteristic curve analysis.
      CONCLUSIONS: The findings of this study suggest four potential metabolites as
      biomarkers for OSCC screening.

PMID- 30282896
TI  - Analysis of Forming Limits in Sheet Metal Forming with Pattern Recognition
      Methods. Part 2: Unsupervised Methodology and Application.
AB  - The forming limit curve (FLC) is used in finite element analysis (FEA) for the
      modeling of onset of sheet metal instability during forming. The FLC is usually
      evaluated by achieving forming measurements with optical measurement system
      during Nakajima tests. Current evaluation methods such as the standard method
      according to DIN EN ISO 12004-2 and time-dependent methods limit the evaluation
      range to a fraction of the available information and show weaknesses in the
      context of brittle materials that do not have a pronounced constriction phase. In
      order to meet these challenges, a supervised pattern recognition method was
      proposed, whose results depend on the quality of the expert annotations. In order
      to alleviate this dependence on experts, this study proposes an unsupervised
      classification approach that does not require expert annotations and allows a
      probabilistic evaluation of the onset of localized necking. For this purpose, the
      results of the Nakajima tests are examined with an optical measuring system and
      evaluated using an unsupervised classification method. In order to assess the
      quality of the results, a comparison is made with the time-dependent method
      proposed by Volk and Hora, as well as expert annotations, while validated with
      metallographic investigations. Two evaluation methods are presented, the
      deterministic FLC, which provides a lower and upper limit for the onset of
      necking, and a probabilistic FLC, which allows definition of failure quantiles.
      Both methods provide a necking range that shows good correlation with the expert
      opinion as well as the results of the time-dependent method and metallographic
      examinations.

PMID- 30282897
TI  - "Farewell to the God of Plague": The Importance of Political Commitment Towards
      the Elimination of Schistosomiasis.

PMID- 30282898
TI  - Compliance with 24-h Movement Behaviour Guidelines among Belgian Pre-School
      Children: The ToyBox-Study.
AB  - The 24-h day-containing physical activity, sedentary behaviour and sleep-in pre
      school children has not yet been extensively investigated. The aim of the current
      study was to investigate pre-schoolers' compliance with the 24-h movement
      behaviour guidelines (i.e., three hours/day total physical activity, a maximum of
      one hour/day of screen time and 10-13 h sleep/night). In total, 595 pre-schoolers
      (53.3% boys, mean age: 4.2 years) provided complete data for the three
      behaviours. Physical activity was objectively measured with accelerometers, while
      screen time and sleep were parent-reported through questionnaires. The proportion
      of pre-schoolers complying with the 24-h movement behaviour guidelines was
      calculated on weekdays and on weekend days. Low compliance rates were found:
      10.1% on weekdays and only 4.3% on weekend days. The majority of pre-schoolers
      complied with the sleep duration guidelines (>90% on weekdays and weekend days),
      followed by the screen time guidelines (61% on weekdays and 28% on weekend days).
      The lowest compliance rates were found for physical activity (<20% on weekdays
      and weekend days). Overall, low percentages of pre-schoolers complying with the
      24-h movement behaviour guidelines were found, and the lowest compliance was
      found for physical activity.

PMID- 30282899
TI  - A Study on Neonatal Intake of Oleanolic Acid and Metformin in Rats (Rattus
      norvegicus) with Metabolic Dysfunction: Implications on Lipid Metabolism and
      Glucose Transport.
AB  - : Metabolic syndrome, a cluster of different disorders which include diabetes,
      obesity and cardiovascular diseases, is a global epidemic that is growing at an
      alarming rate. The origins of disease can be traced back to early developmental
      stages of life. This has increased mortalities and continues to reduce life
      expectancies of individuals across the globe. The aim of this study was to
      investigate the sub-acute and long term effects of neonatal oral administration
      of oleanolic acid and metformin on lipids (free fatty acids, FFAs) and genes
      associated with lipid metabolism and glucose transport using a neonatal rat
      experimental model. In the first study, seven days old pups were randomly grouped
      into control-distilled water (DW); oleanolic acid (60 mg/kg), metformin (500
      mg/kg), high fructose diet (20% w/v, HF), oleanolic acid (OA) + high fructose
      diet (OA + HF), and Metformin + high fructose diet (MET + HF) groups. The pups
      were treated for 7 days, and then terminated on postnatal day (PD) 14. In the
      second study, rat pups were initially treated similarly to study 1 and weaned
      onto normal rat chow and plain drinking water on PD 21 till they reached
      adulthood (PD112). Tissue and blood samples were collected for further analyses.
      Measurement of the levels of free fatty acids (FFAs) was done using gas
      chromatography-mass spectrometry. Quantitative polymerase chain reaction (qPCR)
      was used to analyze the gene expression of glut-4, glut-5, fas, acc-1, nrf-1 and
      cpt-1 in the skeletal muscle. The results showed that HF accelerated accumulation
      of saturated FFAs within skeletal muscles. The HF fed neonatal rats had increased
      stearic acid, which was associated with decreased glucose, suppressed expression
      of glut-4, glut-5, nrf-1 and cpt-1 genes, and increased expression of acc-1 (p <
      0.01) and fas. OA + HF and MET + HF treated groups had increased mono- and
      polyunsaturated FFAs; oleic, and octadecadienoic acids than the HF group. These
      unsaturated FFAs were associated with increased glut-4, glut-5 and nrf-1 (p <
      0.01) and decreased acc-1 and fas (p < 0.05) in both OA + HF and MET + HF treated
      groups. CONCLUSIONS: The present study shows that neonatal oral administration of
      oleanolic acid and metformin potentially protects against the development of
      fructose-induced metabolic dysfunction in the rats in both short and long time
      periods.

PMID- 30282900
TI  - Social and Emotional Fears and Worries Influencing the Quality of Life of Female
      Celiac Disease Patients Following a Gluten-Free Diet.
AB  - The gluten-free diet is effective in the majority of celiac disease (CD)
      patients, but it is burdensome and may influence quality of life (QoL). The aim
      of the study was to analyze the social and emotional fears and worries
      influencing the QoL of female CD patients following a gluten-free (GF) diet, as
      well as to indicate the sociodemographic interfering factors. The study was
      conducted on a group of 251 female CD patients, while emotional, social and
      worries subscales of the Celiac Disease Questionnaire (CDQ) were applied, as well
      as purchase-related emotions and behaviors were assessed. Respondents declaring
      worse economic status obtained significantly lower scores in the emotional,
      social and worries subscales of the CDQ than respondents declaring better
      economic status, while for other factors (CD duration, GFD adherence, BMI, place
      of residence and educational level) no significant association was stated in the
      multi-factor analysis. Moreover, respondents declaring worse economic status more
      often declared that a bad mood affected their purchase decisions than did
      respondents declaring better economic status. It was stated, that the economic
      status of CD patient could be one of the most important factors influencing their
      social and emotional fears and worries. It may be supposed that low economic
      status may lead some CD patients to choose to relieve stress by purchasing GF
      products instead of other products.

PMID- 30282901
TI  - Effects of a Change from an Indoor-Based Total Mixed Ration to a Rotational
      Pasture System Combined with a Moderate Concentrate Feed Supply on the Health and
      Performance of Dairy Cows.
AB  - In spring, the transition from a total mixed ration (TMR) to pasture requires
      metabolic adaptions for the cow. It had been shown that supply of low amounts of
      concentrate after transition to full-time grazing caused energy deficits,
      resulting in a lower milking performance and changes in a variety of variables
      indicative for energy metabolism. The present study aimed to investigate how a
      moderate concentrate supply (4.5 kg dry matter cow/day) after transition to
      pasture influences health and production indicators. Over a 12-week trial period
      dairy cows were observed during transition from confinement to pasture (pasture
      group: PG) and compared to cows fed TMR indoors (confinement group: CG). On
      average, the PG consumed less feed and energy than the CG and mobilized body
      reserves, which is mirrored in a decrease of body condition and various fat
      depots. These effects were paralleled by elevated serum concentrations of non
      esterified fatty acids and ketone bodies as well as an increase in liver fat
      content. The physical activity (elevated walking, eating, decreasing rumination
      time) of the PG was significantly higher than that of the CG, which intensified
      the energy deficiency and resulted in a lower milk yield. In conclusion, the
      moderate concentrate supply was insufficient to counterbalance the lower energy
      intake from pasture during transition.

PMID- 30282902
TI  - Luteolin Targets the Toll-Like Receptor Signaling Pathway in Prevention of
      Hepatic and Adipocyte Fibrosis and Insulin Resistance in Diet-Induced Obese Mice.
AB  - This study was to investigate the protective role of luteolin on inflammation
      mediated metabolic diseases, focusing on the role of luteolin in the modulation
      of the Toll-like receptor (TLR) signaling pathway. C57BL/6J mice were fed a
      normal, high-fat, or high-fat + 0.005% (w/w) luteolin diet for 16 weeks. Luteolin
      improved chronic low-grade inflammation by modulating the TLR signaling pathway,
      resulting in reduced pro-inflammatory cytokines and macrophage accumulation. A
      positive relationship was detected between gene expressions of Tlr5, Map2k7,
      Mapk12, Mapk13, and Mapk9 and lipogenesis in epididymal white adipose tissue
      (eWAT) of luteolin-treated mice, which was linked to attenuation of hepatic
      lipotoxicity by increasing free fatty acid (FFA) flux to the WAT. Luteolin
      prevented fibrosis by decreasing extracellular matrix accumulation and cathepsin
      gene expressions, while enhancing the hepatic antioxidant system. Emr1 and Ccl7,
      important markers inducing low-grade inflammation, were affected by advanced age
      and greater body weight, which were normalized by luteolin treatment. Luteolin
      improved insulin resistance by normalizing pancreatic islet dysfunction and
      differentially modulating the plasma glucagon-like peptide-1 and gastric
      inhibitory polypeptide levels. Our results suggest that luteolin ameliorates diet
      induced obesity and its comorbidities. Overall, this study provides novel
      insights into the effect of luteolin on the links among adiposopathy, insulin
      resistance, hepatic steatosis, and fibrosis.

PMID- 30282903
TI  - Prescribing Variation in General Practices in England Following a Direct
      Healthcare Professional Communication on Mirabegron.
AB  - INTRODUCTION: Pharmacovigilance may detect safety issues after marketing of
      medications, and this can result in regulatory action such as direct healthcare
      professional communications (DHPC). DHPC can be effective in changing prescribing
      behaviour, however the extent to which prescribers vary in their response to DHPC
      is unknown. This study aims to explore changes in prescribing and prescribing
      variation among general practitioner (GP) practices following a DHPC on the
      safety of mirabegron, a medication to treat overactive bladder (OAB). METHODS:
      This is an interrupted time series study of English GP practices from 2014-2017.
      National Health Service (NHS) Digital provided monthly statistics on aggregate
      practice-level prescribing and practice characteristics (practice staff and
      registered patient profiles, Quality and Outcomes Framework indicators, and
      deprivation of the practice area). The primary outcome was monthly mirabegron
      prescriptions as a percentage of all OAB drug prescriptions and we assessed the
      change following a DHPC issued by the European Medicines Agency in September
      2015. The DHPC stated mirabegron use was contraindicated with severe uncontrolled
      hypertension and cautioned with hypertension. Variation between practices in
      mirabegron prescribing before and after the DHPC was assessed using the
      systematic component of variation (SCV). Multilevel segmented regression with
      random effects quantified the change in level and trend of prescribing after the
      DHPC. Practice characteristics were assessed for their association with a
      reduction in prescribing following the DHPC. RESULTS: This study included 7408
      practices. During September 2015, 88.9% of practices prescribed mirabegron and
      mirabegron comprised a mean of 8.2% (SD 6.8) of OAB prescriptions. Variation
      between practices was classified as very high and the median SCV did not change
      significantly (p = 0.11) in the six months after the September 2015 DHPC (12.4)
      compared to before (11.6). Before the DHPC, the share of mirabegron over all OAB
      drug prescriptions increased by 0.294 (95% confidence interval (CI), 0.287,
      0.301) percentage points per month. There was no significant change in the month
      immediately after the DHPC (-0.023, 95% CI -0.105 to 0.058), however there was a
      significant reduction in trend (-0.036, 95% CI -0.049 to -0.023). Higher numbers
      of registered patients, patients aged >=65 years, and practice area deprivation
      were associated with having a significant decrease in level and slope of
      mirabegron prescribing post-DHPC. CONCLUSION: Variation in mirabegron prescribing
      was high over the study period and did not change substantively following the
      DHPC. There was no immediate prescribing change post-DHPC, although the monthly
      growth did slow. Knowledge of the degree of variation in and determinants of
      response to safety communications may allow those that do not change prescribing
      habits to be provided with additional support.

PMID- 30282905
TI  - Effects of Short Transport and Prolonged Fasting in Beef Calves.
AB  - Marketing is a stressful process for beef calves, because they are removed from
      their environment, often weaned just before loading, loaded, transported, and
      unloaded. It also involves extended periods without food and water and mixing
      with unfamiliar animals in an unknown environment. Some studies have shown that
      calves sold through markets are exposed to extended fasting periods even when
      they undergo only short transportation times. The aim of this controlled study
      was to determine the consequences for beef calves of a short transportation time
      followed by a prolonged time without food and water on their tympanic temperature
      (TT), maximum eye temperature (MET), blood variables related to stress, and live
      weight. Ten calves were transported for 3 h and then kept in an outdoor pen for
      21 h, completing a 24 h fasting period. Sampling took place before loading, after
      transport and unloading, and then after completing 24 h without food and water.
      TT, MET, blood glucose, and creatine kinase (CK) increased significantly after
      transportation. Live weight decreased across sample times (mean of 10 kg per calf
      after 24 h of fasting), which was consistent with the higher concentration of
      beta-HB found after fasting. Further studies to measure the actual consequences
      of true, commercial marketing on calf welfare and productivity are needed.

PMID- 30282904
TI  - 10,12 Conjugated Linoleic Acid-Driven Weight Loss Is Protective against
      Atherosclerosis in Mice and Is Associated with Alternative Macrophage Enrichment
      in Perivascular Adipose Tissue.
AB  - The dietary fatty acid 10,12 conjugated linoleic acid (10,12 CLA) promotes weight
      loss by increasing fat oxidation, but its effects on atherosclerosis are less
      clear. We recently showed that weight loss induced by 10,12 CLA in an
      atherosclerosis-susceptible mouse model with characteristics similar to human
      metabolic syndrome is accompanied by accumulation of alternatively activated
      macrophages within subcutaneous adipose tissue. The objective of this study was
      to evaluate whether 10,12 CLA-mediated weight loss was associated with an
      atheroprotective phenotype. Male low-density lipoprotein receptor deficient (Ldlr
      /-) mice were made obese with 12 weeks of a high-fat, high-sucrose diet feeding
      (HFHS: 36% fat, 36% sucrose, 0.15% added cholesterol), then either continued on
      the HFHS diet with or without caloric restriction (CR), or switched to a diet
      with 1% of the lard replaced by either 9,11 CLA or 10,12 CLA for 8 weeks.
      Atherosclerosis and lipid levels were quantified at sacrifice. Weight loss in
      mice following 10,12 CLA supplementation or CR as a weight-matched control group
      had improved cholesterol and triglyceride levels, yet only the 10,12 CLA-treated
      mice had improved en face and aortic sinus atherosclerosis. 10,12 CLA
      supplemented mice had increased lesion macrophage content, with enrichment of
      surrounding perivascular adipose tissue (PVAT) alternative macrophages, which may
      contribute to the anti-atherosclerotic effect of 10,12 CLA.

PMID- 30282906
TI  - Simultaneous Intake of Euglena Gracilis and Vegetables Synergistically Exerts an
      Anti-Inflammatory Effect and Attenuates Visceral Fat Accumulation by Affecting
      Gut Microbiota in Mice.
AB  - We determined whether the benefits provided by the consumption of Euglena
      gracilis (Euglena), which is a unicellular photosynthesizing green alga and rich
      in insoluble dietary fiber paramylon, can be enhanced by the co-consumption of
      vegetables that are rich in soluble dietary fiber. Nine-week-old male C57BL/6J
      mice were divided into four groups: group 1 received normal diet, whereas groups
      2, 3 and 4 received normal diet containing 0.3% paramylon, 1.0% Euglena, or 1.0%
      Euglena plus 0.3% vegetables (barley leaf, kale and ashitaba), respectively. Mice
      were fed ad libitum until 18 weeks of age. Euglena intake significantly decreased
      serum markers of inflammation and co-consumption of vegetables enhanced this
      reduction. Notably, we observed an increase in the fraction of beneficial
      bacteria producing short-chain fatty acids, a reduction in harmful bacteria that
      cause inflammation and an increase in short-chain fatty acid production. Visceral
      fat accumulation was also reduced. Subsequent analyses showed that co-consumption
      of Euglena with vegetables reduced adipocyte area, suppressed the expression of
      genes related to fatty acid synthesis and increased the expression of genes
      related to adipocyte growth and lipolysis. Therefore, co-consumption of Euglena
      with vegetables enhanced its anti-inflammatory effect and the inhibitory effect
      on visceral fat accumulation likely by modulating the composition of gut
      microbiota.

PMID- 30282909
TI  - "I Feel Sorry for Them": Australian Meat Consumers' Perceptions about Sheep and
      Beef Cattle Transportation.
AB  - Concern for livestock welfare is significantly increasing in many parts of the
      world. One area of concern is the transportation of livestock. Using qualitative
      research methods, this research explores the concerns of Australian meat
      consumers related to livestock transportation practices, both on land by truck
      and on sea by ship. Participants were predominantly concerned about animals being
      "crammed" into trucks and ships, and the long distances over which livestock were
      transported. Likely contributors to these reactions are the high visibility of
      truck transport in urban areas, and recent media and political attention to the
      live-export issue in Australia. We argue that participants' concerns about
      transport are arising for a variety of reasons, including anthropomorphic
      tendencies, genuine concern for the welfare of farm animals, and emotional
      responses related to the discomfort experienced by meat consumers when they are
      reminded of the meat-animal connection. Given the importance of transport to the
      red-meat production industry, these results suggest that the sector may need to
      reconsider some of their practices and increase transparency and communication
      about the practices, which they utilise to ensure good animal welfare.

PMID- 30282907
TI  - Rubella Virus Strain-Associated Differences in the Induction of Oxidative Stress
      Are Independent of Their Interferon Activation.
AB  - Rubella virus (RV) infection impacts cellular metabolic activity in a complex
      manner with strain-specific nutritional requirements. Here we addressed whether
      this differential metabolic influence was associated with differences in
      oxidative stress induction and subsequently with innate immune response
      activation. The low passaged clinical isolates of RV examined in this study
      induced oxidative stress as validated through generation of the reactive oxygen
      species (ROS) cytoplasmic hydrogen peroxide and mitochondrial superoxide. The
      addition of the cytoplasmic and mitochondrial ROS scavengers N-acetyl-l-cysteine
      and MitoTEMPO, respectively, reduced RV-associated cytopathogenicity and caspase
      activation. While the degree of oxidative stress induction varied among RV
      clinical isolates, the level of innate immune response and interferon-stimulated
      gene activation was comparable. The type III IFNs were highly upregulated in all
      cell culture systems tested. However, only pre-stimulation with IFN beta slightly
      reduced RV replication indicating that RV appears to have evolved the ability to
      counteract innate immune response mechanisms. Through the data presented, we
      showed that the ability of RV to induce oxidative stress was independent of its
      capacity to stimulate and counteract the intrinsic innate immune response.

PMID- 30282908
TI  - APS8 Delays Tumor Growth in Mice by Inducing Apoptosis of Lung Adenocarcinoma
      Cells Expressing High Number of alpha7 Nicotinic Receptors.
AB  - The alkylpyridinium polymer APS8, a potent antagonist of alpha7 nicotinic
      acetylcholine receptors (nAChRs), selectively induces apoptosis in non-small cell
      lung cancer cells but not in normal lung fibroblasts. To explore the potential
      therapeutic value of APS8 for at least certain types of lung cancer, we
      determined its systemic and organ-specific toxicity in mice, evaluated its
      antitumor activity against adenocarcinoma xenograft models, and examined the in
      vitro mechanisms of APS8 in terms of apoptosis, cytotoxicity, and viability. We
      also measured Ca2+ influx into cells, and evaluated the effects of APS8 on Ca2+
      uptake while siRNA silencing of the gene for alpha7 nAChRs, CHRNA7. APS8 was not
      toxic to mice up to 5 mg/kg i.v., and no significant histological changes were
      observed in mice that survived APS8 treatment. Repetitive intratumoral injections
      of APS8 (4 mg/kg) significantly delayed growth of A549 cell tumors, and generally
      prevented regrowth of tumors, but were less effective in reducing growth of HT29
      cell tumors. APS8 impaired the viability of A549 cells in a dose-dependent manner
      and induced apoptosis at micro molar concentrations. Nano molar APS8 caused minor
      cytotoxic effects, while cell lysis occurred at APS8 >3 uM. Furthermore, Ca2+
      uptake was significantly reduced in APS8-treated A549 cells. Observed differences
      in response to APS8 can be attributed to the number of alpha7 nAChRs expressed in
      these cells, with those with more AChRs (i.e., A549 cells) being more sensitive
      to nAChR antagonists like APS8. We conclude that alpha7 nAChR antagonists like
      APS8 have potential to be used as therapeutics for tumors expressing large
      numbers of alpha7 nAChRs.

PMID- 30282911
TI  - Metabolomic Analyses Reveal Extensive Progenitor Cell Deficiencies in a Mouse
      Model of Duchenne Muscular Dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a musculoskeletal disorder that causes
      severe morbidity and reduced lifespan. Individuals with DMD have an X-linked
      mutation that impairs their ability to produce functional dystrophin protein in
      muscle. No cure exists for this disease and the few therapies that are available
      do not dramatically delay disease progression. Thus, there is a need to better
      understand the mechanisms underlying DMD which may ultimately lead to improved
      treatment options. The muscular dystrophy (MDX) mouse model is frequently used to
      explore DMD disease traits. Though some studies of metabolism in dystrophic mice
      exist, few have characterized metabolic profiles of supporting cells in the
      diseased environment. Using nontargeted metabolomics we characterized metabolic
      alterations in muscle satellite cells (SCs) and serum of MDX mice. Additionally,
      live-cell imaging revealed MDX-derived adipose progenitor cell (APC) defects.
      Finally, metabolomic studies revealed a striking elevation of acylcarnitines in
      MDX APCs, which we show can inhibit APC proliferation. Together, these studies
      highlight widespread metabolic alterations in multiple progenitor cell types and
      serum from MDX mice and implicate dystrophy-associated metabolite imbalances in
      APCs as a potential contributor to adipose tissue disequilibrium in DMD.

PMID- 30282910
TI  - Environmental Electronic Vape Exposure from Four Different Generations of
      Electronic Cigarettes: Airborne Particulate Matter Levels.
AB  - Electronic cigarettes (e-cigs) were introduced into the market in 2006 and their
      technological features have evolved substantially over time. Currently, there are
      four different generations of e-cigs that are broadly considered less harmful
      than the use of combusted tobacco products although passive exposure to aerosols
      often occurs in public spaces and indoor environments. The study aim was to
      evaluate the levels of airborne particulate matter (PM) emitted during the use of
      all the four generations of e-cigs, testing different use modalities. PM10, PM4,
      PM2.5 and PM1 were measured through a Dusttrak TM II Aerosol Monitor, for a total
      of 20 independent experiments. All tested e-cigs devices produced PM during their
      use, and PM10 was almost made of PM1 size fraction. In addition, we observed a
      progressive increase in PM emission from the first to the fourth generation, and
      an upward trend of PM1 emitted by the fourth generation e-cig with an increase in
      the operating power. The results showed that, whatever the model adopted, passive
      vaping does occur. This finding supports the need for legislative interventions
      to regulate the e-cigs use in public places and other enclosed environments, in
      order to protect the health of any subject who is potentially exposed.

PMID- 30282912
TI  - Milieu for Endothelial Differentiation of Human Adipose-Derived Stem Cells.
AB  - Human adipose-derived stem cells (hASCs) have been shown to differentiate down
      many lineages including endothelial lineage. We hypothesized that hASCs would
      more efficiently differentiate toward the endothelial lineage when formed as
      three-dimensional (3D) spheroids and with the addition of vascular endothelial
      growth factor (VEGF). Three conditions were tested: uncoated tissue culture
      polystyrene (TCPS) surfaces that induced a 2D monolayer formation; elastin-like
      polypeptide (ELP)-collagen composite hydrogel scaffolds that induced encapsulated
      3D spheroid culture; and ELP-polyethyleneimine-coated TCPS surfaces that induced
      3D spheroid formation in scaffold-free condition. Cells were exposed to
      endothelial differentiation medium containing no additional VEGF or 20 and 50
      ng/mL of VEGF for 7 days and assayed for viability and endothelial
      differentiation markers. While endothelial differentiation media supported
      endothelial differentiation of hASCs, our 3D spheroid cultures augmented this
      differentiation and produced more von Willebrand factor than 2D cultures.
      Likewise, 3D cultures were able to uptake LDL, whereas the 2D cultures were not.
      Higher concentrations of VEGF further enhanced differentiation. Establishing
      angiogenesis is a key factor in regenerative medicine. Future studies aim to
      elucidate how to produce physiological changes such as neoangiogenesis and
      sprouting of vessels which may enhance the survival of regenerated tissues.

PMID- 30282913
TI  - Computer-Aided Studies for Novel Arylhydantoin 1,3,5-Triazine Derivatives as 5
      HT6 Serotonin Receptor Ligands with Antidepressive-Like, Anxiolytic and
      Antiobesity Action In Vivo.
AB  - This study focuses on the design, synthesis, biological evaluation, and computer
      aided structure-activity relationship (SAR) analysis for a novel group of
      aromatic triazine-methylpiperazines, with an hydantoin spacer between 1,3,5
      traizine and the aromatic fragment. New compounds were synthesized and their
      affinities for serotonin 5-HT6, 5-HT1A, 5-HT2A, 5-HT7, and dopamine D2 receptors
      were evaluated. The induced-fit docking (IFD) procedure was performed to explore
      the 5-HT6 receptor conformation space employing two lead structures. It resulted
      in a consistent binding mode with the activity data. For the most active
      compounds found in each modification line, anti-obesity and anti-depressive-like
      activity in vivo, as well as "druglikeness" in vitro, were examined. Two 2
      naphthyl compounds (18 and 26) were identified as the most active 5-HT6R agents
      within each lead modification line, respectively. The 5-(2-naphthyl)hydantoin
      derivative 26, the most active one in the series (5-HT6R: Ki = 87 nM), displayed
      also significant selectivity towards competitive G-protein coupled receptors (6
      197-fold). Docking studies indicated that the hydantoin ring is stabilized by
      hydrogen bonding, but due to its different orientation, the hydrogen bonds form
      with S5.44 and N6.55 or Q6.58 for 18 and 26, respectively. Compound 26 exerted
      anxiolytic-like and antidepressant-like activities. Importantly, it demonstrated
      anti-obesity properties in animals fed palatable feed, and did not show toxic
      effects in vitro.

PMID- 30282916
TI  - Anti-Diabetic Medications for the Pharmacologic Management of NAFLD.
AB  - As a chronic disease encompassing a wide spectrum of liver-related histologic
      damage, nonalcoholic fatty liver disease (NAFLD) is becoming a global epidemic
      with significant impacts on all-cause morbidity and mortality. Insulin resistance
      and type 2 diabetes mellitus predispose individuals to NAFLD and related
      complications. Therefore, timely intervention with anti-diabetic medications may
      prevent and delay the development of NAFLD or have a therapeutic implication. The
      focus of this review is to evaluate the evidence supporting the efficacy of anti
      diabetic medications in the treatment of NAFLD. While many of these anti-diabetic
      agents have shown to improve biochemical parameters, their effect on hepatic
      histology is limited. Among anti-diabetic medications, only thiazolidinediones
      and glucagon-like peptide-1 receptor agonists demonstrate significant improvement
      in hepatic histology.

PMID- 30282915
TI  - Prodigiosin-Emerged PI3K/Beclin-1-Independent Pathway Elicits Autophagic Cell
      Death in Doxorubicin-Sensitive and -Resistant Lung Cancer.
AB  - Prodigiosin (PG) belongs to a family of prodiginines isolated from gram-negative
      bacteria. It is a water insoluble red pigment and a potent proapoptotic compound.
      This study elucidates the anti-tumor activity and underlying mechanism of PG in
      doxorubicin-sensitive (Dox-S) and doxorubicin-resistant (Dox-R) lung cancer
      cells. The cytotoxicity and cell death characteristics of PG in two cells were
      measured by MTT assay, cell cycle analysis, and apoptosis/autophagic marker
      analysis. Then, the potential mechanism of PG-induced cell death was evaluated
      through the phosphatidylinositol-4,5-bisphosphate 3-kinase-p85/Protein kinase B
      /mammalian target of rapamycin (PI3K-p85/Akt/mTOR) and Beclin
      1/phosphatidylinositol-4,5-bisphosphate 3-kinase-Class III (Beclin-1/PI3K-Class
      III) signaling. Finally, in vivo efficacy was examined by intratracheal
      inoculation and treatment. There was similar cytotoxicity with PG in both Dox-S
      and Dox-R cells, where the half maximal inhibitory concentrations (IC50) were all
      in 10 MUM. Based on a non-significant increase in the sub-G1 phase with an
      increase of microtubule-associated proteins 1A/1B light chain 3B
      phosphatidylethanolamine conjugate (LC3-II), the cell death of both cells was
      categorized to achieve autophagy. Interestingly, an increase in cleaved-poly ADP
      ribose polymerase (cleaved-PARP) also showed the existence of an apoptosis
      sensitive subpopulation. In both Dox-S and Dox-R cells, PI3K-p85/Akt/mTOR
      signaling pathways were reduced, which inhibited autophagy initiation. However,
      Beclin-1/PI3K-Class III downregulation implicated non-canonical autophagy
      pathways were involved in PG-induced autophagy. At completion of the PG regimen,
      tumors accumulated in the mice trachea and were attenuated by PG treatment, which
      indicated the efficacy of PG for both Dox-S and Dox-R lung cancer. All the above
      results concluded that PG is a potential chemotherapeutic agent for lung cancer
      regimens regardless of doxorubicin resistance.

PMID- 30282914
TI  - Molecular and Immunohistochemical Markers with Prognostic and Predictive
      Significance in Liver Metastases from Colorectal Carcinoma.
AB  - Despite the significant recent achievements in the diagnosis and treatment of
      colorectal cancer (CRC), the prognosis of these patients has currently plateaued.
      During the past few years, the opportunity to consider multiple treatment
      modalities (including surgery and other locoregional treatments, systemic
      therapy, and targeted therapy) led to the research of novel prognostic and
      predictive biomarkers in CRC liver metastases (CRCLM) patients. In this review,
      we seek to describe the current state of knowledge of CRCLM biomarkers and to
      outline impending clinical perspectives, in particular focusing on the cutting
      edge tools available for their characterization.

PMID- 30282917
TI  - Effect of Selected Commercial Plasticizers on Mechanical, Thermal, and
      Morphological Properties of Poly(3-hydroxybutyrate)/Poly(lactic acid)/Plasticizer
      Biodegradable Blends for Three-Dimensional (3D) Print.
AB  - This paper explores the influence of selected commercial plasticizers structure,
      which are based on esters of citric acid, on mechanical and thermal properties of
      Poly(3-hydroxybutyrate)/Poly(lactic acid)/Plasticizer biodegradable blends. These
      plasticizers were first tested with respect to their miscibility with Poly(3
      hydroxybutyrate)/Poly(lactic acid) (PHB/PLA) blends using a kneading machine.
      PHB/PLA/plasticizer blends in the weight ratio (wt %) of 60/25/15 were then
      prepared by single screw and corotating meshing twin screw extruders in the form
      of filament for further three-dimensional (3D) printing. Mechanical, thermal
      properties, and shape stability (warping effect) of 3D printed products can be
      improved just by the addition of appropriate plasticizer to polymeric blend. The
      goal was to create new types of eco-friendly PHB/PLA/plasticizers blends and to
      highly improve the poor mechanical properties of neat PHB/PLA blends (with
      majority of PHB) by adding appropriate plasticizer. Mechanical properties of
      plasticized blends were then determined by the tensile test of 3D printed test
      samples (dogbones), as well as filaments. Measured elongation at break rapidly
      enhanced from 21% for neat non-plasticized PHB/PLA blends (reference) to 328% for
      best plasticized blends in the form of filament, and from 5% (reference) to 187%
      for plasticized blends in the form of printed dogbones. The plasticizing effect
      on blends was confirmed by Modulated Differential Scanning Calorimetry. The study
      of morphology was performed by the Scanning Electron Microscopy. Significant
      problem of plasticized blends used to be also plasticizer migration, therefore
      the diffusion of plasticizers from the blends after 15 days of exposition to 110 
      degrees C in the drying oven was investigated as their measured weight loss.
      Almost all of the used plasticizers showed meaningful positive softening effects,
      but the diffusion of plasticizers at 110  degrees C exposition was quite
      extensive. The determination of the degree of disintegration of selected
      plasticized blend when exposed to a laboratory-scale composting environment was
      executed to roughly check the "biodegradability".

PMID- 30282918
TI  - N Balance Studies Emphasize the Superior Protein Quality of Pig Diets at High
      Inclusion Level of Algae Meal (Spirulina platensis) or Insect Meal (Hermetia
      illucens) when Adequate Amino Acid Supplementation Is Ensured.
AB  - Two age-dependent nitrogen (N) balance studies (average body mass 25 and 60 kg)
      utilized 16 male castrated piglets and 16 barrows to measure N utilization
      parameters of diets with complete substitution of SBM by alternative protein
      sources (SM, HM), but different AA fortifications. Lysine supplementation up to
      80% of the recommended lysine (Lys) supply in diets HM (A) and SM (A) yielded
      similar protein quality data (63.6 +/- 2.1 and 63.7 +/- 3.4). Surprisingly, only
      in piglet diet HM (AA) did the extended AA supplementation (Lys, methionine
      (Met), threonine (Thr)) enhance protein quality (72.8 +/- 6.7) significantly (p =
      0.004). Similar trends were observed in growing pigs. However, when the level of
      histidine (His) in diet SM (AA) was increased, feed protein quality (71.8 +/-
      1.3) was significantly (p < 0.001) improved indicating the importance of adequate
      His supply in diets with a complete substitution of SBM by the algae meal (SM)
      under study. AA efficiency data extend the possibilities to explain the observed
      responses on protein quality. When an adequate AA balancing in the diet is
      guaranteed, from nutritional point of view both of the alternative proteins may
      replace SBM in pig diets.

PMID- 30282919
TI  - Fetal Brain Infection Is Not a Unique Characteristic of Brazilian Zika Viruses.
AB  - The recent emergence of Zika virus (ZIKV) in Brazil was associated with an
      increased number of fetal brain infections that resulted in a spectrum of
      congenital neurological complications known as congenital Zika syndrome (CZS).
      Herein, we generated de novo from sequence data an early Asian lineage ZIKV
      isolate (ZIKV-MY; Malaysia, 1966) not associated with microcephaly and compared
      the in vitro replication kinetics and fetal brain infection in interferon
      alpha/beta receptor 1 knockout (IFNAR1-/-) dams of this isolate and of a
      Brazilian isolate (ZIKV-Natal; Natal, 2015) unequivocally associated with
      microcephaly. The replication efficiencies of ZIKV-MY and ZIKV-Natal in A549 and
      Vero cells were similar, while ZIKV-MY replicated more efficiently in wild-type
      (WT) and IFNAR-/- mouse embryonic fibroblasts. Viremias in IFNAR1-/- dams were
      similar after infection with ZIKV-MY or ZIKV-Natal, and importantly, infection of
      fetal brains was also not significantly different. Thus, fetal brain infection
      does not appear to be a unique feature of Brazilian ZIKV isolates.

PMID- 30282921
TI  - Preparation of Reduction-Responsive Camptothecin Nanocapsules by Combining
      Nanoprecipitation and In Situ Polymerization for Anticancer Therapy.
AB  - Stimuli-responsive systems for controlled drug release have been extensively
      explored in recent years. In this work, we developed a reduction-responsive
      camptothecin (CPT) nanocapsule (CPT-NC) by combining nanoprecipitation and in
      situ polymerization using a polymerized surface ligand and a disulfide bond
      containing crosslinker. Dissolution rate studies proved that the CPT-NCs have
      robust drug-release profiles in the presence of glutathione (GSH) owing to the
      division of the disulfide bond crosslinker which triggers the collapse of the
      polymer layer. Furthermore, the in vitro investigations demonstrated that the CPT
      NCs exhibited a high-cellular uptake efficiency and cytotoxicity for cancer cells
      of squamous cell carcinoma (SCC-15). Our approach thus presents an effective
      intracellular drug delivery strategy for anticancer therapy.

PMID- 30282922
TI  - Consuming Genistein Improves Survival Rates in the Absence of Laxative in
      DeltaF508-CF Female Mice.
AB  - Genistein is a naturally occurring isoflavone found in soy. Genistein has been
      shown to increase the open probability of the most common cystic fibrosis (CF)
      disease-associated mutation, ?F508-CFTR. Mice homozygous for the ?F508 mutation
      are characterized with severe intestinal disease and require constant laxative
      treatment for survival. This pathology mimics the intestinal obstruction
      (meconium ileus) seen in some cystic fibrosis patients. This study tested whether
      dietary supplementation with genistein would reduce the dependence of the ?F508
      CF mouse model on laxatives for survival, thereby improving mortality rates. At
      weaning (21 days), homozygous ?F508 mice were maintained on one of three diet
      regimens for a period of up to 65 days: normal diet, normal diet plus colyte, or
      genistein diet. Survival rates for males were as follows: standard diet (38%, n =
      21), standard diet plus colyte (83%, n = 42) and genistein diet (60%, n = 15).
      Survival rates for females were as follows: standard diet (47%, n = 19), standard
      diet plus colyte (71%, n = 38), and genistein diet (87%, n = 15). Average weight
      of male mice fed genistein diet increased by ~2.5 g more (p = 0.006) compared to
      those with colyte treatment. Genistein diet did not change final body weight of
      females. Expression of intestinal SGLT-1 increased 2-fold (p = 0.0005) with
      genistein diet in females (no change in males, p = 0.722). Expression of GLUT2
      and GLUT5 was comparable between all diet groups. Genistein diet reduced the
      number of goblet cells per micrometer of crypt depth in female (p = 0.0483), yet
      was without effect in males (p = 0.7267). The results from this study demonstrate
      that supplementation of diet with genistein for ~45 days increases the survival
      rate of female ?F508-CF mice (precluding the requirement for laxatives), and
      genistein only improves weight gain in males.

PMID- 30282920
TI  - Oxidative Stress in the Male Germline: A Review of Novel Strategies to Reduce 4
      Hydroxynonenal Production.
AB  - Germline oxidative stress is intimately linked to several reproductive
      pathologies including a failure of sperm-egg recognition. The lipid aldehyde 4
      hydroxynonenal (4HNE) is particularly damaging to the process of sperm-egg
      recognition as it compromises the function and the stability of several germline
      proteins. Considering mature spermatozoa do not have the capacity for de novo
      protein translation, 4HNE modification of proteins in the mature gametes has
      uniquely severe consequences for protein homeostasis, cell function and cell
      survival. In somatic cells, 4HNE overproduction has been attributed to the action
      of lipoxygenase enzymes that facilitate the oxygenation and degradation of omega
      6 polyunsaturated fatty acids (PUFAs). Accordingly, the arachidonate 15
      lipoxygenase (ALOX15) enzyme has been intrinsically linked with 4HNE production,
      and resultant pathophysiology in various complex conditions such as coronary
      artery disease and multiple sclerosis. While ALOX15 has not been well
      characterized in germ cells, we postulate that ALOX15 inhibition may pose a new
      strategy to prevent 4HNE-induced protein modifications in the male germline. In
      this light, this review focuses on (i) 4HNE-induced protein damage in the male
      germline and its implications for fertility; and (ii) new methods for the
      prevention of lipid peroxidation in germ cells.

PMID- 30282923
TI  - QSAR and Classification Study on Prediction of Acute Oral Toxicity of N-Nitroso
      Compounds.
AB  - To better understand the mechanism of in vivo toxicity of N-nitroso compounds
      (NNCs), the toxicity data of 80 NNCs related to their rat acute oral toxicity
      data (50% lethal dose concentration, LD50) were used to establish quantitative
      structure-activity relationship (QSAR) and classification models. Quantum
      chemistry methods calculated descriptors and Dragon descriptors were combined to
      describe the molecular information of all compounds. Genetic algorithm (GA) and
      multiple linear regression (MLR) analyses were combined to develop QSAR models.
      Fingerprints and machine learning methods were used to establish classification
      models. The quality and predictive performance of all established models were
      evaluated by internal and external validation techniques. The best GA-MLR-based
      QSAR model containing eight molecular descriptors was obtained with Q2loo =
      0.7533, R2 = 0.8071, Q2ext = 0.7041 and R2ext = 0.7195. The results derived from
      QSAR studies showed that the acute oral toxicity of NNCs mainly depends on three
      factors, namely, the polarizability, the ionization potential (IP) and the
      presence/absence and frequency of C-O bond. For classification studies, the best
      model was obtained using the MACCS keys fingerprint combined with artificial
      neural network (ANN) algorithm. The classification models suggested that several
      representative substructures, including nitrile, hetero N nonbasic, alkylchloride
      and amine-containing fragments are main contributors for the high toxicity of
      NNCs. Overall, the developed QSAR and classification models of the rat acute oral
      toxicity of NNCs showed satisfying predictive abilities. The results provide an
      insight into the understanding of the toxicity mechanism of NNCs in vivo, which
      might be used for a preliminary assessment of NNCs toxicity to mammals.

PMID- 30282924
TI  - Fish Intake, Circulating Mercury and Mortality in Renal Transplant Recipients.
AB  - Marine-derived omega-3 polyunsaturated fatty acids (n-3 PUFAs) are inversely
      associated with cardiovascular and all-cause mortality in renal transplant
      recipients (RTRs). Recommendations to increase marine-derived n-3 PUFAs by
      increasing fish intake may have a drawback in concomitant stimulation of mercury
      intake, which could lead to higher circulating mercury concentrations and
      mitigation of otherwise beneficial effects of n-3 PUFAs. We aimed to monitor
      circulating mercury concentrations, and to prospectively evaluate whether it
      counteracts the potential association between fish intake and cardiovascular and
      all-cause mortality in a cohort of RTRs (n = 604, 53 +/- 13 years-old, 57% men)
      with long-term follow-up (median of 5.4 years; 121 deaths). Circulating mercury
      concentration (median 0.30 (IQR 0.14-0.63) ug/L) positively associated with fish
      intake (std. beta = 0.21, p < 0.001). Multivariable-adjusted Cox-proportional
      hazards regression analyses showed that prior to, and after additional adjustment
      for circulating mercury concentrations, fish intake was inversely associated with
      both cardiovascular (HR 0.75, 95% CI 0.58-0.96; and, HR 0.75, 95% CI 0.58-0.97,
      respectively) and all-cause mortality (HR 0.84, 95% CI 0.72-0.97; and, HR 0.86,
      95% CI 0.74-0.99, respectively). Secondary analyses accounting for marine-derived
      n-3 PUFAs intake revealed associations of similar magnitude. In conclusion, we
      found no evidence of a counteracting effect conferred by circulating mercury
      concentrations on the associations between fish and marine-derived n-3 PUFAs
      intake and the risks of cardiovascular and all-cause mortality in RTRs.

PMID- 30282925
TI  - Effect of Natural Food Antioxidants against LDL and DNA Oxidative Changes.
AB  - Radical oxygen species formed in human tissue cells by many endogenous and
      exogenous pathways cause extensive oxidative damage which has been linked to
      various human diseases. This review paper provides an overview of lipid
      peroxidation and focuses on the free radicals-initiated processes of low-density
      lipoprotein (LDL) oxidative modification and DNA oxidative damage, which are
      widely associated with the initiation and development of atherosclerosis and
      carcinogenesis, respectively. The article subsequently provides an overview of
      the recent human trials or even in vitro investigations on the potential of
      natural antioxidant compounds (such as carotenoids; vitamins C and E) to monitor
      LDL and DNA oxidative changes.

PMID- 30282927
TI  - New Nitrogen Compounds Coupled to Phenolic Units with Antioxidant and Antifungal
      Activities: Synthesis and Structure-Activity Relationship.
AB  - A selection of 1-amino-2-arylidenamine-1,2-(dicyano)ethenes 3 was synthesized and
      cyclized to 2-aryl-4,5-dicyano-1H-imidazoles 4 upon reflux in ethyl
      acetate/acetonitrile, in the presence of manganese dioxide. These compounds were
      tested for their antioxidant capacity by cyclic voltammetry, 2,2-diphenyl-1
      picrylhydrazyl (DPPH) radical and deoxyribose degradation assays. The minimum
      inhibitory concentration of all compounds was evaluated against two yeast
      species, Saccharomyces cerevisiae and Candida albicans. Their toxicity was tested
      in mammal fibroblasts. Among the synthesised compounds, two presented dual
      antioxidant/antifungal activity without toxic effects in fibroblasts. The new
      compounds synthesized in this work are potential biochemical tools and/or
      therapeutic drugs.

PMID- 30282926
TI  - Nucleic Acid-Dependent Structural Transition of the Intrinsically Disordered N
      Terminal Appended Domain of Human Lysyl-tRNA Synthetase.
AB  - Eukaryotic lysyl-tRNA synthetases (LysRS) have an N-terminal appended tRNA
      interaction domain (RID) that is absent in their prokaryotic counterparts. This
      domain is intrinsically disordered and lacks stable structures. The disorder-to
      order transition is induced by tRNA binding and has implications on folding and
      subsequent assembly into multi-tRNA synthetase complexes. Here, we expressed and
      purified RID from human LysRS (hRID) in Escherichia coli and performed a detailed
      mutagenesis of the appended domain. hRID was co-purified with nucleic acids
      during Ni-affinity purification, and cumulative mutations on critical amino acid
      residues abolished RNA binding. Furthermore, we identified a structural ensemble
      between disordered and helical structures in non-RNA-binding mutants and an
      equilibrium shift for wild-type into the helical conformation upon RNA binding.
      Since mutations that disrupted RNA binding led to an increase in non-functional
      soluble aggregates, a stabilized RNA-mediated structural transition of the N
      terminal appended domain may have implications on the functional organization of
      human LysRS and multi-tRNA synthetase complexes in vivo.

PMID- 30282929
TI  - Bioactive Compounds and Antioxidant Capacity of Rosa rugosa Depending on Degree
      of Ripeness.
AB  - Maturity stage affects the bioactive compounds as well as the antioxidant
      capacity in the fruit. This study was designed to identify and quantify
      carotenoids, as well as to evaluate vitamin E, vitamin C, antioxidant capacity
      and total phenolic compounds of Rosa rugosa hips at different degrees of
      ripeness. HPLC (high performance liquid chromatography) analysis showed different
      types of carotenoids at different stages of maturity of R. rugosa hips with
      significant differences (p ? 0.05), where the maximum concentration was observed
      at late harvesting. In the hips investigated, only alpha-tocopherol was detected,
      the maximum concentration of both vitamin E and vitamin C was obtained in the
      orange hips with significant difference (p ? 0.05). On the other hand, the
      highest hydrophilic and lipophilic TEAC (Trolox equivalent antioxidant capacity)
      values, as well as total phenolic contents, were determined in the mature hips
      (red colour) with significant difference (p < 0.0001) and (p < 0.001)
      respectively, whereas ORAC (oxygen radical absorbance capacity) showed lower
      activity in the mature hips with significant difference (p ? 0.05). Late
      harvesting is recommended if a high content of carotenoids is desired, while
      harvesting should be carried out earlier if a higher vitamin E and vitamin C
      content is desired, which in turn affects the antioxidants capacity.

PMID- 30282928
TI  - Effect of Ivabradine on a Hypertensive Heart and the Renin-Angiotensin
      Aldosterone System in L-NAME-Induced Hypertension.
AB  - Ivabradine, the selective inhibitor of the If current in the sinoatrial node,
      exerts cardiovascular protection by its bradycardic effect and potentially
      pleiotropic actions. However, there is a shortage of data regarding ivabradine's
      interaction with the renin-angiotensin-aldosterone system (RAAS). This study
      investigated whether ivabradine is able to protect a hypertensive heart in the
      model of L-NAME-induced hypertension and to interfere with the RAAS. Four groups
      (n = 10/group) of adult male Wistar rats were treated as follows for four weeks:
      control, ivabradine (10 mg/kg/day), L-NAME (40 mg/kg/day), and L-NAME plus
      ivabradine. L-NAME administration increased systolic blood pressure (SBP) and
      left ventricular (LV) weight, enhanced hydroxyproline concentration in the LV,
      and deteriorated the systolic and diastolic LV function. Ivabradine reduced heart
      rate (HR) and SBP, and improved the LV function. The serum concentrations of
      angiotensin Ang 1-8 (Ang II), Ang 1-5, Ang 1-7, Ang 1-10, Ang 2-8, and Ang 3-8
      were decreased in the L-NAME group and ivabradine did not modify them. The serum
      concentration of aldosterone and the aldosterone/Ang II ratio were enhanced by L
      NAME and ivabradine reduced these changes. We conclude that ivabradine improved
      the LV function of the hypertensive heart in L-NAME-induced hypertension. The
      protective effect of ivabradine might have been associated with the reduction of
      the aldosterone level.

PMID- 30282930
TI  - Validation of a Drug-Related Problem Classification System for the Intermediate
      and Long-Term Care Setting in Singapore.
AB  - : Background: This study aims to evaluate the inter-rater reliability and
      perceived usability of a newly developed drug-related problem (DRP)
      classification system for use by pharmacists in the intermediate and long-term
      care (ILTC) setting in Singapore. METHODS: This was a cross-sectional survey
      study involving the use of a self-administered questionnaire. All 55 pharmacists
      affiliated to the Pharmaceutical Society of Singapore (PSS) ILTC Pharmacists
      Workgroup who were above 21 years old and not authors of the classification
      system were invited to participate. The inter-rater reliability of participants'
      classification of 46 mock DRP cases using the new DRP classification system was
      determined using Fleiss's kappa (kappa). Participants' perceived usability of the
      classification system was evaluated using six items with five-point Likert scales
      (1-"strongly disagree", 5-"strongly agree"). Results: Thirty-three pharmacists
      responded to the survey. Overall inter-rater reliability was found to be
      substantial (kappa = 0.614; 95% CI: 0.611-0.617). All usability items received
      positive ratings ("strongly agree" or "agree") from at least 69% of participants.
      Conclusion: The new DRP classification system has substantial external validity
      and appears to be suitable for use by pharmacists to document and report DRPs in
      the ILTC setting in Singapore and facilitate evaluation of the impact of
      pharmaceutical care in the ILTC setting.

PMID- 30282931
TI  - Glycogen Storage Disease Ib and Severe Periodontal Destruction: A Case Report.
AB  - Background: Glycogen storage diseases (GSDs) are genetic disorders that result
      from defects in the processing of glycogen synthesis or breakdown within muscles,
      liver, and other cell types. It also manifests with impaired neutrophil
      chemotaxis and neutropenic episodes which results in severe destruction of the
      supporting dental tissues, namely the periodontium. Although GSD Type Ib cannot
      be cured, associated symptoms and debilitating oral manifestations of the disease
      can be managed through collaborative medical and dental care where early
      detection and intervention is of key importance. This objective of the case
      report was to describe a child with GSD Ib and its associated oral manifestations
      with microbial, immunological and histological appearances. Case Presentation: An
      eight-year-old Hispanic male with a history of GSD type Ib presented with
      extensive intraoral generalized inflammation of the gingiva, ulcerations and
      bleeding, and intraoral radiographic evidence of bone loss. Tannerella forsythia
      was readily identifiable from the biofilm samples. Peripheral blood neutrophils
      were isolated and a deficient host response was observed by impaired neutrophil
      migration. Histological evaluation of the soft and hard tissues of the
      periodontally affected primary teeth showed unaffected dentin and cementum.
      Conclusions: This case illustrates the association between GSD Ib and oral
      manifestations of the disease. A multi-disciplinary treatment approach was
      developed in order to establish healthy intraoral conditions for the patient.
      Review of the literature identified several cases describing GSD and its clinical
      and radiographic oral manifestations; however, none was identified where also
      microbial, immunological, and histological appearances were described.

PMID- 30282932
TI  - Measurement of Core Body Temperature Using Graphene-Inked Infrared Thermopile
      Sensor.
AB  - Continuous and reliable measurements of core body temperature (CBT) are vital for
      studies on human thermoregulation. Because tympanic membrane directly reflects
      the temperature of the carotid artery, it is an accurate and non-invasive method
      to record CBT. However, commercial tympanic thermometers lack portability and
      continuous measurements. In this study, graphene inks were utilized to increase
      the accuracy of the temperature measurements from the ear by coating graphene
      platelets on the lens of an infrared thermopile sensor. The proposed ear-based
      device was designed by investigating ear canal geometry and developed with 3D
      printing technology using the Computer-Aided Design (CAD) Software, SolidWorks
      2016. It employs an Arduino Pro Mini and a Bluetooth module. The proposed system
      runs with a 3.7 V, 850 mAh rechargeable lithium-polymer battery that allows long
      term, continuous monitoring. Raw data are continuously and wirelessly plotted on
      a mobile phone app. The test was performed on 10 subjects under resting and
      exercising in a total period of 25 min. Achieved results were compared with the
      commercially available Braun Thermoscan, Original Thermopile, and Cosinuss One
      ear thermometers. It is also comprehended that such system will be useful in
      personalized medicine as wearable in-ear device with wireless connectivity.

PMID- 30282934
TI  - Synergism of Mild Heat and High-Pressure Pasteurization Against Listeria
      monocytogenes and Natural Microflora in Phosphate-Buffered Saline and Raw Milk.
AB  - As many as 99% of illnesses caused by Listeria monocytogenes are foodborne in
      nature, leading to 94% hospitalizations, and are responsible for the collective
      annual deaths of 266 American adults. The current study is a summary of
      microbiological hurdle validation studies to investigate synergism of mild heat
      (up to 55  degrees C) and elevated hydrostatic pressure (up to 380 MPa) for
      decontamination of Listeria monocytogenes and natural background microflora in
      raw milk and phosphate-buffered saline. At 380 MPa, for treatments of 0 to 12
      min, d-values of 3.47, 3.15, and 2.94 were observed for inactivation of the
      pathogen at 4, 25, and 50  degrees C. Up to 3.73 and >4.26 log CFU/mL reductions
      (p < 0.05) of habituated Listeria monocytogenes were achieved using pressure at
      380 MPa for 3 and 12 min, respectively. Similarly, background microflora counts
      were reduced (p < 0.05) by 1.3 and >2.4 log CFU/mL after treatments at 380 MPa
      for 3 and 12 min, respectively. Treatments below three min were less efficacious
      (p >= 0.05) against the pathogen and background microflora, in the vast majority
      of time and pressure combinations. Results of this study could be incorporated as
      part of a risk-based food safety management system and risk assessment analyses
      for mitigating the public health burden of listeriosis.

PMID- 30282933
TI  - Cell Cycle Changes after Glioblastoma Stem Cell Irradiation: The Major Role of
      RAD51.
AB  - "Glioma Stem Cells" (GSCs) are known to play a role in glioblastoma (GBM)
      recurrence. Homologous recombination (HR) defects and cell cycle checkpoint
      abnormalities can contribute concurrently to the radioresistance of GSCs. DNA
      repair protein RAD51 homolog 1 (RAD51) is a crucial protein for HR and its
      inhibition has been shown to sensitize GSCs to irradiation. The aim of this study
      was to examine the consequences of ionizing radiation (IR) for cell cycle
      progression in GSCs. In addition, we intended to assess the potential effect of
      RAD51 inhibition on cell cycle progression. Five radiosensitive GSC lines and
      five GSC lines that were previously characterized as radioresistant were exposed
      to 4Gy IR, and cell cycle analysis was done by fluorescence-activated cell
      sorting (FACS) at 24, 48, 72, and 96 h with or without RAD51 inhibitor. Following
      4Gy IR, all GSC lines presented a significant increase in G2 phase at 24 h, which
      was maintained over 72 h. In the presence of RAD51 inhibitor, radioresistant GSCs
      showed delayed G2 arrest post-irradiation for up to 48 h. This study demonstrates
      that all GSCs can promote G2 arrest in response to radiation-induced DNA damage.
      However, following RAD51 inhibition, the cell cycle checkpoint response differed.
      This study contributes to the characterization of the radioresistance mechanisms
      of GSCs, thereby supporting the rationale of targeting RAD51-dependent repair
      pathways in view of radiosensitizing GSCs.

PMID- 30282935
TI  - Polysulfone/Polyamide-SiO2 Composite Membrane with High Permeance for Organic
      Solvent Nanofiltration.
AB  - To improve the filtration performance and properties of organic solvent
      nanofiltration (OSN) membranes, we firstly introduce nanoporous silica (SiO2)
      particles into the polyamide (PA) active layer of polysulfone (PSf) membrane via
      an interfacial polymerization process. Results from the study revealed that
      introduction of SiO2 influenced the properties of PSf/PA-SiO2 composite membranes
      by changing the surface roughness and hydrophilicity. Moreover, results also
      indicated that nanoporous SiO2 modified membranes showed an improved performance
      of alcohols solvent permeance. The PSf/PA-SiO2 composite membrane modified by
      0.025 wt % of SiO2 reached a permeance of 3.29 L m-2 h-1 bar-1 for methanol and
      0.42 L m-2 h-1 bar-1 for ethanol, which were 20.0% and 13.5% higher than the
      control PSf membrane (permeance of 2.74 L m-2 h-1 bar-1 for methanol and 0.37 L m
      2 h-1 bar-1 for ethanol). Conclusively, we demonstrated that the increase of
      membrane hydrophilicity and roughness were major factors contributing to the
      improved alcohols solvent permeance of the membranes.

PMID- 30282936
TI  - Multimodal Ligand Binding Studies of Human and Mouse G-Coupled Taste Receptors to
      Correlate Their Species-Specific Sweetness Tasting Properties.
AB  - Taste signaling is a complex process that is linked to obesity and its associated
      metabolic syndromes. The sweet taste is mediated through a heterodimeric G
      protein coupled receptor (GPCR) in a species-specific manner and at multi-tissue
      specific levels. The sweet receptor recognizes a large number of ligands with
      structural and functional diversities to modulate different amplitudes of
      downstream signaling pathway(s). The human sweet-taste receptor has been
      extremely difficult to study by biophysical methods due to the difficulty in
      producing large homogeneous quantities of the taste-receptor protein and the lack
      of reliable in vitro assays to precisely measure productive ligand binding modes
      that lead to activation of the receptor protein. We report here a multimodal high
      throughput assay to monitor ligand binding, receptor stability and conformational
      changes to model the molecular ligand-receptor interactions. We applied
      saturation transfer difference nuclear magnetic resonance spectroscopy (STD-NMR)
      complemented by differential scanning calorimetry (DSC), circular dichroism (CD)
      spectroscopy, and intrinsic fluorescence spectroscopy (IF) to characterize
      binding interactions. Our method using complementary NMR and biophysical analysis
      is advantageous to study the mechanism of ligand binding and signaling processes
      in other GPCRs.

PMID- 30282937
TI  - BMCGM: A Behavior Economics-Based Message Transmission Cooperation Guarantee
      Mechanism in Vehicular Ad-hoc NETworks.
AB  - Vehicular Ad-hoc NETwork (VANET) is a special mobile ad hoc network that composed
      of facilities such as vehicle nodes and roadside units. Message transfer among
      vehicle nodes has been a great challenge due to the network's highly variable
      topology and the selfish nature of vehicle nodes. Thus, it is very necessary to
      propose a mechanism to improve the cooperation among vehicle nodes to guarantee
      the effective message transmission. Currently, incentive-based cooperation
      mechanisms are commonly used to encourage nodes to participate in message
      transmission. Those mechanisms are based on traditional economics and generally
      assume that the decision-making behavior of nodes is completely independent.
      Also, the cooperation of nodes depends on whether the cooperation behavior can
      obtain the higher utility. But researches in behavioral economics have shown that
      due to the existence of altruistic reciprocity, the behavior of nodes is affected
      by not only their utility but also the behavioral motives of other nodes, so as
      to obtain different results from traditional incentive-based mechanisms.
      Therefore, the paper introduces the reciprocal altruistic from behavioral
      economics and proposes the reciprocal altruistic factor to reconstruct the
      utility function of nodes. The reconstructed utility function reflects the
      interaction of behavioral motives among nodes, which promotes the node's
      cooperative behavior. Also, since the Network Formation Game (NFG) is a common
      mathematical model for studying the interaction and communication links formation
      among network nodes, hence the paper regards NFG in traditional economics as the
      research object. A Behavior Economics-based Message Transmission Cooperation
      Guarantee Mechanism named BMCGM is proposed, which motivates nodes to participate
      in the message transmission to reduce the transmission delay ratio. The
      simulation results show that the BMCGM reduces message transmission delay by at
      least 30.3% compared with the recent representative cooperation transmission
      mechanism.

PMID- 30282938
TI  - An Infrastructure-Free Indoor Localization Algorithm for Smartphones.
AB  - Accurate indoor positioning technology provides location-based service for a
      variety of applications. However, most existing indoor localization approaches
      (e.g., Wi-Fi and Bluetooth-based methods) rely heavily on positioning
      infrastructure, which prevents their large-scale deployment and limits the range
      at which they are applicable. Here, we proposed an infrastructure-free indoor
      positioning and tracking approach, termed LiMag, which used ubiquitous magnetic
      field and ambient lights (e.g., fluorescent, incandescent, and light-emitting
      diodes (LEDs)) without containing modulated information. We conducted an in-depth
      study on both the advantages and the challenges in leveraging magnetic field and
      ambient light intensity for indoor localization. Based on the insights from this
      study, we established a hybrid observation model that took full advantage of both
      the magnetic field and ambient light signals. To address the low discernibility
      of the hybrid observation model, LiMag first generated a single-step fingerprint
      model by vectorizing consecutive hybrid observations within each step. In order
      to accurately track users, a lightweight single-step tracking algorithm based on
      the single-step fingerprints and the particle filter framework was designed.
      LiMag leveraged the walking information of users and several single-step
      fingerprints to generate long trajectory fingerprints that exhibited much higher
      location differentiation ability than the single-step fingerprint. To accelerate
      particle convergence and eliminate the accumulative error of single-step tracking
      algorithm, a long trajectory calibration scheme based on long trajectory
      fingerprints was also introduced. An undirected weighted graph model was
      constructed to decrease the computational overhead resulting from this long
      trajectory matching. In addition to typical indoor scenarios including offices,
      shopping malls and parking lots, we also conducted experiments in more
      challenging scenarios, including large open-plan areas as well as environments
      characterized by strong sunlight. Our proposed algorithm achieved a 75th
      percentile localization accuracy of 1.8 m and 2.2 m, respectively, in the office
      and shopping mall tested. In conclusion, our LiMag algorithm provided location
      based service of infrastructure-free with significantly improved localization
      accuracy and coverage, as well as satisfactory robustness inside complex indoor
      environments.

PMID- 30282939
TI  - Design of Amphibious Vehicle for Unmanned Mission in Water Quality Monitoring
      Using Internet of Things.
AB  - Unmanned aerial vehicles (UAVs) have gained significant attention in recent times
      due to their suitability for a wide variety of civil, military, and societal
      missions. Development of an unmanned amphibious vehicle integrating the features
      of a multi-rotor UAV and a hovercraft is the focus of the present study.
      Components and subsystems of the amphibious vehicle are developed with due
      consideration for aerodynamic, structural, and environmental aspects. Finite
      element analysis (FEA) on static thrust conditions and skirt pressure are
      performed to evaluate the strength of the structure. For diverse wind conditions
      and angles of attack (AOA), computational fluid dynamic (CFD) analysis is carried
      out to assess the effect of drag and suitable design modification is suggested. A
      prototype is built with a 7 kg payload capacity and successfully tested for
      stable operations in flight and water-borne modes. Internet of things (IoT) based
      water quality measurement is performed in a typical lake and water quality is
      measured using pH, dissolved oxygen (DO), turbidity, and electrical conductivity
      (EC) sensors. The developed vehicle is expected to meet functional requirements
      of disaster missions catering to the water quality monitoring of large water
      bodies.

PMID- 30282941
TI  - Effect of ZrO2 Nanomaterials on Wettability and Interfacial Characteristics of Al
      19Cu-11Si-2Sn Filler Metal for Low Temperature Al to Cu Dissimilar Brazing.
AB  - Dissimilar Al 3003 and Cu tubular components were successfully brazed without
      interface cracking using ZrO2 nanomaterials reinforced with Al-19Cu-11Si-2Sn
      filler. The filler was initially cast using an induction furnace and processed
      into ring form for brazing. Al-19Cu-11Si-2Sn filler with coarse CuAl2 and Si
      phases (43 and 20 MUm) were refined to 8 and 4 MUm, respectively, after the
      addition of 0.1 wt. % ZrO2 and shows significant improvement in the mechanical
      properties. ZrO2 nanomaterials' induced diffusion controlled growth mechanism is
      found be the responsible for the refinement of CuAl2 intermetallic and Si
      particles. The wettability of Al-19Cu-11Si-2Sn-0.1ZrO2 increased to 78.17% on Cu
      side and 93.19% on the Al side compared from 74.8% and 89.9%, respectively.
      Increase in the yield strength, ultimate tensile strength, and percentage
      elongation were noted for the brazed joints. Microstructure of induction brazed
      joint with 40 kW for 6 seconds using Al-19Cu-11Si-2Sn-0.1ZrO2 filler shows thin
      interfacial CuAl2 intermetallic compound along the copper side and inter
      diffusion region along the aluminum side and their respective mechanism is
      discussed. The tensile strength of the joints increased with increasing the
      nanomaterials addition and shows a base metal fracture. Analysis of fractured
      samples shows the effectiveness of ZrO2 reinforced filler in crack propagation
      through the filler.

PMID- 30282940
TI  - Review of the Electrical Characterization of Metallic Nanowires on DNA Templates.
AB  - The use of self-assembly techniques may open new possibilities in scaling down
      electronic circuits to their ultimate limits. Deoxyribonucleic acid (DNA)
      nanotechnology has already demonstrated that it can provide valuable tools for
      the creation of nanostructures of arbitrary shape, therefore presenting an ideal
      platform for the development of nanoelectronic circuits. So far, however, the
      electronic properties of DNA nanostructures are mostly insulating, thus limiting
      the use of the nanostructures in electronic circuits. Therefore, methods have
      been investigated that use the DNA nanostructures as templates for the deposition
      of electrically conducting materials along the DNA strands. The most simple such
      structure is given by metallic nanowires formed by deposition of metals along the
      DNA nanostructures. Here, we review the fabrication and the characterization of
      the electronic properties of nanowires, which were created using these methods.

PMID- 30282942
TI  - Magnetostrictive Properties of Mn0.70Zn0.24Fe2.06O4 Ferrite.
AB  - This paper presents the results of measurements of magnetostrictive properties of
      Mn0.70Zn0.24Fe2.06O4 ferrite for power applications. Frame-shaped samples were
      used for measurements to guarantee a uniform magnetizing field and
      magnetostrictive strain distribution. Magnetostrictive hysteresis loops were
      measured by semiconductor strain gauges. The results indicate that the
      magnetostrictive characteristic of Mn0.70Zn0.24Fe2.06O4 ferrite is non-monotonic
      and magnetostriction changes have opposite signs for higher values of the
      magnetizing field.

PMID- 30282943
TI  - Shotgun Lipidomics Revealed Altered Profiles of Serum Lipids in Systemic Lupus
      Erythematosus Closely Associated with Disease Activity.
AB  - The pathogenesis of systemic lupus erythematosus (SLE) remains elusive. It
      appears that serum lipid metabolism is aberrant in SLE patients. Determination of
      lipid profiles in the serum of SLE patients may provide insights into the
      underlying mechanism(s) leading to SLE and may discover potential biomarkers for
      early diagnosis of SLE. This study aimed to identify and quantify the profile of
      serum lipids in SLE patients (N = 30) with our powerful multi-dimensional mass
      spectrometry-based shotgun lipidomics platform. Multivariate analysis in the form
      of partial least squares-discriminate analysis was performed, and the
      associations between the changed lipids with cytokines and SLE disease activity
      index (SLEDAI) were analyzed using a multiple regression method. The results of
      this study indicated that the composition of lipid species including diacyl
      phosphatidylethanolamine (dPE) (16:0/18:2, 18:0/18:2, 16:0/22:6, 18:0/20:4, and
      18:0/22:6), 18:2 lysoPC (LPC), and ceramide (N22:0 and N24:1) was significantly
      altered in SLE patients with p < 0.05 and variable importance of the projection
      (VIP) > 1 in partial least squares-discriminate analysis (PLS-DA). There existed
      significant associations between IL-10, and both 18:0/18:2 and 16:0/22:6 dPE
      species with p < 0.0001 and predicting 85.7 and 95.8% of the variability of IL-10
      levels, respectively. All the altered lipid species could obviously predict IL-10
      levels with F (8, 21) = 3.729, p = 0.007, and R2 = 0.766. There was also a
      significant correlation between the SLEDAI score and 18:0/18:2 dPE (p = 0.031)
      with explaining 22.6% of the variability of SLEDAI score. Therefore, the panel of
      changed compositions of dPE and ceramide species may serve as additional
      biomarkers for early diagnosis and/or prognosis of SLE.

PMID- 30282944
TI  - A Fast Neighbor Discovery Algorithm in WSNs.
AB  - With the quick development of Internet of Things (IoT), one of its important
      supporting technologies, i.e., wireless sensor networks (WSNs), gets much more
      attention. Neighbor discovery is an indispensable procedure in WSNs. The existing
      deterministic neighbor discovery algorithms in WSNs ensure that successful
      discovery can be obtained within a given period of time, but the average
      discovery delay is long. It is difficult to meet the need for rapid discovery in
      mobile low duty cycle environments. In addition, with the rapid development of
      IoT, the node densities of many WSNs greatly increase. In such scenarios,
      existing neighbor discovery methods fail to satisfy the requirement in terms of
      discovery latency under the condition of the same energy consumption. This paper
      proposes a group-based fast neighbor discovery algorithm (GBFA) to address the
      issues. By carrying neighbor information in beacon packet, the node knows in
      advance some potential neighbors. It selects more energy efficient potential
      neighbors and proactively makes nodes wake up to verify whether these potential
      neighbors are true neighbors, thereby speeding up neighbor discovery, improving
      energy utilization efficiency and decreasing network communication load. The
      evaluation results indicate that, compared with other methods, GBFA decreases the
      average discovery latency up to 10 . 58 % at the same energy budget.

PMID- 30282945
TI  - The Generated Entropy Monitored by Pyroelectric Sensors.
AB  - Entropy generation in irreversible processes is a critical issue that affects the
      failure and aging of electrical, chemical or mechanical systems. The promotion of
      energy conversion efficiency needs to reduce energy losses, namely to decrease
      entropy generation. A pyroelectric type of entropy detector is proposed to
      monitor energy conversion processes in real time. The entropy generation rate can
      be derived from the induced pyroelectric current, temperature, thermal capacity,
      pyroelectric coefficient and electrode area. It is profitable to design entropy
      detectors to maintain a small thermal capacity while pyroelectric sensors
      minimize geometrical dimensions. Moreover, decreasing the electrode area of the
      PZT cells could avoid affecting the entropy variation of the measured objects,
      but the thickness of the cells has to be greatly reduced to promote the
      temperature variation rate and strengthen the electrical signals. A commercial
      capacitor with a capacitance of 47 MUF and a maximum endured voltage of 4 V were
      used to estimate the entropy to act as an indicator of the capacitors' time-to
      failure. The threshold time was evaluated by using the entropy generation rates
      at about 7.5 s, 11.25 s, 20 s and 30 s for the applied voltages of 40 V, 35 V, 30
      V and 25 V respectively, while using a PZT cell with dimensions of 3 mm square
      and a thickness of 200 MUm.

PMID- 30282946
TI  - Fatigue Performance of RC Beams Strengthened with CFRP under Overloads with a
      Ladder Spectrum.
AB  - Vehicle overload is detrimental to bridges and traffic safety. This paper
      presents a study on the fatigue performance of typical reinforced concrete (RC)
      beams of highway bridges under vehicle overload. A definition method of vehicle
      overload and a construction method of overload ladder spectrum were first
      proposed based on traffic data acquisition, statistical analysis and structural
      calculation of the highway bridges in Guangzhou. A fatigue experimental method
      was also proposed with the three-ladder vehicle overload spectrum, and the
      fatigue tests of 15 RC beams strengthened with carbon fiber reinforced polymer
      (CFRP) under three loading levels were then carried out. The fatigue performance
      and the failure mechanism of the strengthened beams were presented and discussed,
      and two fatigue life prediction methods were proposed with the established
      modified Palmgren-Miner rule and the loading level equivalent method
      respectively. The results showed that the fatigue performance of the strengthened
      RC beams was severely degraded under overload ladder spectrum compared with that
      under constant amplitude cyclic load, and the life prediction methods were proved
      effective.

PMID- 30282947
TI  - Gait Symmetry Assessment with a Low Back 3D Accelerometer in Post-Stroke
      Patients.
AB  - Gait asymmetry is an important marker of mobility impairment post stroke. This
      study proposes a new gait symmetry index (GSI) to quantify gait symmetry with one
      3D accelerometer at L3 (GSIL3). GSIL3 was evaluated with 16 post stroke patients
      and nine healthy controls in the Six-Minute-Walk-Test (6-MWT). Discriminative
      power was evaluated with Wilcoxon test and the effect size (ES) was computed with
      Cliff's Delta. GSIL3 estimated during the entire 6-MWT and during a short segment
      straight walk (GSIL3straight) have comparable effect size to one another (ES =
      0.89, p < 0.001) and to the symmetry indices derived from feet sensors (|ES| =
      [0.22, 0.89]). Furthermore, while none of the indices derived from feet sensors
      showed significant differences between post stroke patients walking with a cane
      compared to those able to walk without, GSIL3 was able to discriminate between
      these two groups with a significantly lower value in the group using a cane (ES =
      0.70, p = 0.02). In addition, GSIL3 was strongly associated with several symmetry
      indices measured by feet sensors during the straight walking cycles (Spearman
      correlation: |rho| = [0.82, 0.88], p < 0.05). The proposed index can be a
      reliable and cost-efficient post stroke gait symmetry assessment with
      implications for research and clinical practice.

PMID- 30282949
TI  - 2'-O-Methylation of Ribosomal RNA: Towards an Epitranscriptomic Control of
      Translation?
AB  - Ribosomal RNA (rRNA) undergoes post-transcriptional modification of over 200
      nucleotides, predominantly 2'-O-methylation (2'-O-Me). 2'-O-Methylation protects
      RNA from hydrolysis and modifies RNA strand flexibility but does not contribute
      to Watson-Crick base pairing. The contribution of 2'-O-Me to the translational
      capacity of ribosomes has been established. Yet, how 2'-O-Me participates in
      ribosome biogenesis and ribosome functioning remains unclear. The development of
      2'-O-Me quantitative mapping methods has contributed to the demonstration that
      these modifications are not constitutive but rather provide heterogeneity to the
      ribosomal population. Moreover, recent advances in ribosome structure analysis
      and in vitro translation assays have proven, for the first time, that 2'-O-Me
      contributes to regulating protein synthesis. This review highlights the recent
      data exploring the impact of 2'-O-Me on ribosome structure and function, and the
      emerging idea that the rRNA epitranscriptome is involved in translational
      control.

PMID- 30282950
TI  - Regional Absorption of Fimasartan in the Gastrointestinal Tract by an Improved in
      situ Absorption Method in Rats.
AB  - The aim of the present study was to assess the regional absorption of fimasartan
      by an improved in situ absorption method in comparison with the conventional in
      situ single-pass perfusion method in rats. After each gastrointestinal segment of
      interest was identified, fimasartan was injected into the starting point of each
      segment and the unabsorbed fimasartan was discharged from the end point of the
      segment. Blood samples were collected from the jugular vein to evaluate the
      systemic absorption of the drug. The relative fraction absorbed (Fabs,relative)
      values in the specific gastrointestinal region calculated based on the area under
      the curve (AUC) values obtained after the injection of fimasartan into the
      gastrointestinal segment were 8.2% +/- 3.2%, 23.0% +/- 12.1%, 49.7% +/- 11.5%,
      and 19.1% +/- 11.9% for the stomach, duodenum, small intestine, and large
      intestine, respectively, which were comparable with those determined by the
      conventional in situ single-pass perfusion. By applying the fraction of the dose
      available at each gastrointestinal segment following the oral administration, the
      actual fraction absorbed (F'abs) values at each gastrointestinal segment were
      estimated at 10.9% for the stomach, 27.1% for the duodenum, 40.7% for the small
      intestine, and 5.4% for the large intestine, which added up to the
      gastrointestinal bioavailability (FX.FG) of 84.1%. The present method holds great
      promise to assess the regional absorption of a drug and aid to design new drug
      formulations.

PMID- 30282951
TI  - A Novel Adaptive Signal Processing Method Based on Enhanced Empirical Wavelet
      Transform Technology.
AB  - Empirical wavelet transform (EWT) is a novel adaptive signal decomposition
      method, whose main shortcoming is the fact that Fourier segmentation is strongly
      dependent on the local maxima of the amplitudes of the Fourier spectrum. An
      enhanced empirical wavelet transform (MSCEWT) based on maximum-minimum length
      curve method is proposed to realize fault diagnosis of motor bearings. The
      maximum-minimum length curve method transforms the original vibration signal
      spectrum to scale space in order to obtain a set of minimum length curves, and
      find the maximum length curve value in the set of the minimum length curve values
      for obtaining the number of the spectrum decomposition intervals. The MSCEWT
      method is used to decompose the vibration signal into a series of intrinsic mode
      functions (IMFs), which are processed by Hilbert transform. Then the frequency of
      each component is extracted by power spectrum and compared with the theoretical
      value of motor bearing fault feature frequency in order to determine and obtain
      fault diagnosis result. In order to verify the effectiveness of the MSCEWT method
      for fault diagnosis, the actual motor bearing vibration signals are selected and
      the empirical mode decomposition (EMD) and ensemble empirical mode decomposition
      (EEMD) methods are selected for comparative analysis in here. The results show
      that the maximum-minimum length curve method can enhance EWT method and the
      MSCEWT method can solve the shortcomings of the Fourier spectrum segmentation and
      can effectively decompose the bearing vibration signal for obtaining less number
      of intrinsic mode function (IMF) components than the EMD and EEMD methods. It can
      effectively extract the fault feature frequency of the motor bearing and realize
      fault diagnosis. Therefore, the study provides a new method for fault diagnosis
      of rotating machinery.

PMID- 30282953
TI  - M-Polynomials and Degree-Based Topological Indices of the Crystallographic
      Structure of Molecules.
AB  - Topological indices are numerical parameters used to study the physical and
      chemical properties of compounds. In quantitative structure-activity relationship
      QSARs, topological indices correlate the biological activity of compounds with
      their physical properties like boiling point, stability, melting point,
      distortion, and strain energy etc. In this paper, we determined the M-polynomials
      of the crystallographic structure of the molecules Cu2O and TiF2 [p,q,r]. Then we
      derived closed formulas for some well-known topological indices using calculus.
      In the end, we used Maple 15 to plot surfaces associated with the topological
      indices of Cu2O and TiF2 [p,q,r].

PMID- 30282952
TI  - Stunting, Beyond Acute Diarrhoea: Giardia Duodenalis, in Cambodia.
AB  - BACKGROUND: The adverse outcomes of malnutrition on the development of a child
      are well acknowledged as are the broad variety of contextual factors that may
      impact child nutritional status. Adequate nutrient intake and the adoption of
      appropriate water, sanitation and hygiene measures are largely documented for
      their positive influence on health. Improved sanitation and protection from human
      feces can significantly lower the incidence of diarrhea and environmental
      enteropathy. However, the impact of excessive exposure to animal feces on child
      health is less well documented. OBJECTIVES: This study tests the hypothesis that
      there is a positive association between exposure to animal feces, morbidity and
      anthropometric outcomes in children under 5 years of age, in Cambodia. It aims to
      improve insights that can contribute to discerning high-impact policies that
      promote children can develop to their full potential. METHODS: Data for this
      study was drawn from the third follow-up round of the MyHealth project cohort
      study that is conducted in six districts of three Cambodian provinces (Phnom
      Penh, Kratie and Ratanak Kiri). The analysis included a sample of 639 children
      under 5 years of age. RESULTS: The presence of livestock and more particularly,
      pigs near the main household dwelling was found a risk factor associated with
      Giardia duodenalis infection (23%). Giardia duodenalis infection was found to be
      a protective factor for acute diarrhea, yet, associated with stunting in the
      univariate model. CONCLUSIONS: Preventive measures that protect from extensive
      exposure to animal feces may be most effective to prevent infection with Giardia
      duodenalis and consequent stunting, thereby improving the potential for a healthy
      development in young Cambodian children. The results support the need for cross
      sector policy measures that reinforce comprehensive early childhood interventions
      towards improving nutritional status as part of a wider set of child welfare and
      development measures.

PMID- 30282954
TI  - Applications of Electrochromic Copolymers Based on Tris(4-carbazoyl-9
      ylphenyl)amine and Bithiophene Derivatives in Electrochromic Devices.
AB  - Four copolymers (P(tCz (tris(4-carbazoyl-9-ylphenyl)amine)-co-bTP (2,2'
      bithiophene)), P(tCz-co-CPDT (4H-cyclopenta[2,1-b:3,4-b']dithiophene)), P(tCz-co
      DTC (3,6-di(2-thienyl)carbazole)), and P(tCz-co-CPDTK (cyclopentadithiophene
      ketone))) are deposited on indium tin oxide (ITO) surfaces using electrochemical
      polymerization. Spectroelectrochemical properties of copolymer electrodes reveal
      that the colors of P(tCz-co-bTP) film are pinkish-orange, light olive green,
      light grayish blue, and dark blue at 0.0, 0.8, 1.2, and 1.6 V, respectively,
      whereas the color variations of P(tCz-co-CPDTK) film are light yellow, yellow,
      and blue at 0.0 V, 0.8 V, and 1.5 V, respectively. The DeltaT of P(tCz-co-bTP),
      P(tCz-co-CPDT), P(tCz-co-DTC), and P(tCz-co-CPDTK) films are estimated to be
      43.0% at 967 nm, 28.7% at 864 nm, 43.6% at 870 nm, and 24.5% at 984 nm,
      respectively. Five electrochromic devices (ECDs) are assembled using the tCz
      based homopolymer and copolymers as coloring electrodes, and poly(2,2-dimethyl
      3,4-propylenedioxythiophene) (PProDOT-Me2) as the complementary electrode. P(tCz
      co-DTC)/PProDOT-Me2 ECD reveals high transmittance change (45.9% at 624 nm),
      P(tCz-co-CPDTK)/PProDOT-Me2 ECD shows high eta (513.0 cm2 C-1 at 582 nm), and
      P(tCz-co-bTP)/PProDOT-Me2 ECD presents short switching time (less than 0.4 s) at
      628 nm. Moreover, these ECDs show satisfactory redox stability and open circuit
      stability.

PMID- 30282948
TI  - Protein Quality Control in the Endoplasmic Reticulum and Cancer.
AB  - The endoplasmic reticulum (ER) is an essential compartment of the biosynthesis,
      folding, assembly, and trafficking of secretory and transmembrane proteins, and
      consequently, eukaryotic cells possess specialized machineries to ensure that the
      ER enables the proteins to acquire adequate folding and maturation for
      maintaining protein homeostasis, a process which is termed proteostasis. However,
      a large variety of physiological and pathological perturbations lead to the
      accumulation of misfolded proteins in the ER, which is referred to as ER stress.
      To resolve ER stress and restore proteostasis, cells have evolutionary conserved
      protein quality-control machineries of the ER, consisting of the unfolded protein
      response (UPR) of the ER, ER-associated degradation (ERAD), and autophagy.
      Furthermore, protein quality-control machineries of the ER play pivotal roles in
      the control of differentiation, progression of cell cycle, inflammation,
      immunity, and aging. Therefore, severe and non-resolvable ER stress is closely
      associated with tumor development, aggressiveness, and response to therapies for
      cancer. In this review, we highlight current knowledge in the molecular
      understanding and physiological relevance of protein quality control of the ER
      and discuss new insights into how protein quality control of the ER is implicated
      in the pathogenesis of cancer, which could contribute to therapeutic intervention
      in cancer.

PMID- 30282955
TI  - Current and Emerging Reconstituted HDL-apoA-I and HDL-apoE Approaches to Treat
      Atherosclerosis.
AB  - Atherosclerosis affects millions of people worldwide. However, the wide variety
      of limitations in the current therapeutic options leaves much to be desired in
      future lipid-lowering therapies. For example, although statins, which are the
      first-line treatment for coronary heart disease (CHD), reduce the risk of
      cardiovascular events in a large percentage of patients, they lead to optimal
      levels of low density lipoprotein-cholesterol (LDL-C) in only about one-third of
      patients. A new promising research direction against atherosclerosis aims to
      improve lipoprotein metabolism. Novel therapeutic approaches are being developed
      to increase the levels of functional high density lipoprotein (HDL) particles.
      This review aims to highlight the atheroprotective potential of the in vitro
      synthesized reconstituted HDL particles containing apolipoprotein E (apoE) as
      their sole apolipoprotein component (rHDL-apoE). For this purpose, we provide:
      (1) a summary of the atheroprotective properties of native plasma HDL and its
      apolipoprotein components, apolipoprotein A-I (apoA-I) and apoE; (2) an overview
      of the anti-atherogenic functions of rHDL-apoA-I and apoA-I-containing HDL, i.e.,
      natural HDL isolated from transgenic Apoa1-/- * Apoe-/- mice overexpressing human
      apoA-I (HDL-apoA-I); and (3) the latest developments and therapeutic potential of
      HDL-apoE and rHDL-apoE. Novel rHDL formulations containing apoE could possibly
      present enhanced biological functions, leading to improved therapeutic efficacy
      against atherosclerosis.

PMID- 30282956
TI  - Derivation and Validation of Machine Learning Approaches to Predict Acute Kidney
      Injury after Cardiac Surgery.
AB  - Machine learning approaches were introduced for better or comparable predictive
      ability than statistical analysis to predict postoperative outcomes. We sought to
      compare the performance of machine learning approaches with that of logistic
      regression analysis to predict acute kidney injury after cardiac surgery. We
      retrospectively reviewed 2010 patients who underwent open heart surgery and
      thoracic aortic surgery. Baseline medical condition, intraoperative anesthesia,
      and surgery-related data were obtained. The primary outcome was postoperative
      acute kidney injury (AKI) defined according to the Kidney Disease Improving
      Global Outcomes criteria. The following machine learning techniques were used:
      decision tree, random forest, extreme gradient boosting, support vector machine,
      neural network classifier, and deep learning. The performance of these techniques
      was compared with that of logistic regression analysis regarding the area under
      the receiver-operating characteristic curve (AUC). During the first postoperative
      week, AKI occurred in 770 patients (38.3%). The best performance regarding AUC
      was achieved by the gradient boosting machine to predict the AKI of all stages
      (0.78, 95% confidence interval (CI) 0.75-0.80) or stage 2 or 3 AKI. The AUC of
      logistic regression analysis was 0.69 (95% CI 0.66-0.72). Decision tree, random
      forest, and support vector machine showed similar performance to logistic
      regression. In our comprehensive comparison of machine learning approaches with
      logistic regression analysis, gradient boosting technique showed the best
      performance with the highest AUC and lower error rate. We developed an Internet
      based risk estimator which could be used for real-time processing of patient data
      to estimate the risk of AKI at the end of surgery.

PMID- 30282958
TI  - A Serological Survey on Swine Brucellosis Using Standard Procedures, Dot Blot,
      and Western Blot in Finisher Pigs in Central-North Italy.
AB  - In recent years, Brucella suis has been sporadically reported in Italy in
      domestic and wild swine. Since standard serological tests can determine false
      positive results, the development of alternative tests with improved sensitivity
      and specificity is rather essential. We analyzed 1212 sera collected at
      slaughterhouse from healthy pigs belonging to 62 farms of North-Central Italy.
      Sera were tested by Rose Bengal Test, Complement Fixation Test, and subsequently
      by a Dot Blot (DB) and Western Blot assays (WB). Only one serum resulted positive
      to all tests, indicating that swine brucellosis has a very limited spread. DB and
      WB could represent a support to the available serological tests; however, further
      studies to validate these tests are needed. In the presence of reemerging
      diseases, a prompt and continuous monitoring design is necessary to acquire
      epidemiological information for the subsequent application of specific health
      emergency plans.

PMID- 30282957
TI  - Correlation between Diabetes Mellitus and Knee Osteoarthritis: A Dry-To-Wet Lab
      Approach.
AB  - Recent years have witnessed an increased prevalence of knee osteoarthritis (KOA)
      among diabetes mellitus (DM) patients-conditions which might share common risk
      factors such as obesity and advanced aging. Therefore, we conducted dry-to-wet
      lab research approaches to assess the correlation of type 1 DM (T1DM) and type 2
      DM (T2DM) with KOA among all age and genders of Taiwanese population. The
      strength of association (odds ratio: OR) was analyzed using a phenome-wide
      association study portal. Populations of 37,353 T1DM and 1,218,254 T2DM were
      included. We observed a significant association of KOA with T1DM (OR: 1.40 (1.33
      1.47), p< 0.0001) and T2DM (OR: 2.75 (2.72-2.78), p< 0.0001). The association
      between T1DM and KOA among the obese (OR: 0.99 (0.54-1.67), p = 0.0477) was
      insignificant compared to the non-obese (OR: 1.40 (1.33-1.48), p < 0.0001).
      Interestingly, a higher association between T2DM and KOA among non-obese persons
      (OR: 2.75, (2.72-2.79), p < 0.0001) compared to the obese (OR: 1.71 (1.55-1.89),
      p < 0.0001) was noted. Further, histopathologic and Western blot studies of
      diabetic mice knee joints revealed enhanced carboxymethyl lysine (advanced
      glycation end product), matrix metalloproteinase-1, and reduced cartilage
      specific proteins, including type II collagen (Col II), SOX9, and aggrecan (AGN),
      indicating deteriorated articular cartilage and proteoglycans. Results indicate
      that DM is strongly associated with KOA, and obesity may not be a confounding
      factor.

PMID- 30282959
TI  - Detection and Monitoring of Insecticide Resistance Mutations in Anopheles
      gambiae: Individual vs Pooled Specimens.
AB  - Bioassays and molecular diagnostics are routinely used for the monitoring of
      malaria vector populations to support insecticide resistance management (IRM),
      guiding operational decisions on which insecticides ought to be used for
      effective vector control. Previously developed TaqMan assays were optimised to
      distinguish the wild-type L1014 from the knockdown resistance (kdr) point
      mutations 1014F and 1014S (triplex reaction), and the N1575 wild-type from the
      point mutation 1575Y (duplex reaction). Subsequently, artificial pools of
      Anopheles gambiae (An. gambiae) specimens with known genotypes of L1014F, L1014S,
      and N1575Y were created, nucleic acids were extracted, and kdr mutations were
      detected. These data were then used to define a linear regression model that
      predicts the allelic frequency within a pool of mosquitoes as a function of the
      measured DeltaCt values (Ct mutant - Ct wild type probe). Polynomial regression
      models showed r2 values of >0.99 (p < 0.05). The method was validated with
      populations of variable allelic frequencies, and found to be precise (1.66
      2.99%), accurate (3.3-5.9%), and able to detect a single heterozygous mosquito
      mixed with 9 wild type individuals in a pool of 10. Its pilot application in
      field-caught samples showed minimal differences from individual genotyping (0.36
      4.0%). It allowed the first detection of the super-kdr mutation N1575Y in An.
      gambiae from Mali. Using pools instead of individuals allows for more efficient
      resistance allele screening, facilitating IRM.

PMID- 30282960
TI  - Combining Microbubble Contrast Agent with Pulsed-Laser Irradiation for
      Transdermal Drug Delivery.
AB  - The optodynamic process of laser-induced microbubble (MB) cavitation in liquids
      is utilized in various medical applications. However, how incident laser
      radiation interacts with MBs as an ultrasound contrast agent is rarely estimated
      when the liquid already contains stable MBs. The present study investigated the
      efficacy of the laser-mediated cavitation of albumin-shelled MBs in enhancing
      transdermal drug delivery. Different types and conditions of laser-mediated
      inertial cavitation of MBs were first evaluated. A CO2 fractional pulsed laser
      was selected for combining with MBs in the in vitro and in vivo experiments. The
      in vitro skin penetration by beta-arbutin after 2 h was 2 times greater in the
      group combining a laser with MBs than in the control group. In small-animal
      experiments, the whitening effect on the skin of C57BL/6J mice in the group
      combining a laser with MBs on the skin plus penetrating beta-arbutin increased
      (significantly) by 48.0% at day 11 and 50.0% at day 14, and then tended to
      stabilize for the remainder of the 20-day experimental period. The present
      results indicate that combining a CO2 laser with albumin-shelled MBs can increase
      skin permeability so as to enhance the delivery of beta-arbutin to inhibit
      melanogenesis in mice without damaging the skin.

PMID- 30282961
TI  - Development of a Multiwavelength Visible-Range-Supported Opto-Ultrasound
      Instrument Using a Light-Emitting Diode and Ultrasound Transducer.
AB  - A new multiwavelength visible-range-supported opto-ultrasound instrument using a
      light-emitting diode and ultrasound transducer was developed in order to produce
      multiwavelength visible light with minimized color aberration errors, and detect
      ultrasound signals emitted from the target. In the instrument, the developed
      optical systems can provide multiwavelength optical transmission with low optical
      aberration within 10-cm ranges that are reasonably flat in the modulation
      transfer function at spatial frequencies of 20 and 40 lp/mm, except at the end of
      the diagonal edge of the samples. To assess the instrument capability, we
      performed pulse-echo responses with Thunnus obesus eye samples. Focused red,
      green, blue and white light rays from an integrated red, green and blue LED
      source were produced, and echo signal amplitudes of 33.53, 34.92, 38.74 and 82.54
      mV, respectively, were detected from the Thunnus obesus eye samples by a 10-MHz
      focused ultrasound transducer. The center frequencies of the echo signal when
      producing red, green, blue and white LED light in the instrument were 9.02, 9.05,
      9.21 and 8.81 MHz, respectively. From these tests, we verify that this instrument
      can combine red, green and blue LED light to cover different wavelengths in the
      visible-light range and detect reasonable echo amplitudes from the samples.

PMID- 30282962
TI  - Emerging Roles of Circular RNAs in Osteosarcoma.
AB  - Osteosarcoma (OS) is a primary malignant bone tumor in early adolescence with
      high metastasis and death rates. Although the combination of polychemotherapy and
      surgical excision increased the survival rates up to 60%, the prognosis remains
      poor for most patients with metastatic or recurrent osteosarcoma. However, the
      exact pathogenic mechanism and pivotal elements regulating tumor invasion and
      metastasis are largely unknown. Circular RNAs (circRNAs) are novel endogenous non
      coding RNA (ncRNA) molecules that generate the cyclic structure from back
      splicing. An increasing number of studies show that circRNAs can regulate
      transcriptional or posttranscriptional gene expression by acting as microRNA
      (miRNA) sponges and are involved in regulation of many important biological
      processes. The deregulation of some circRNAs was demonstrated in osteosarcoma.
      Furthermore, some circRNAs were identified to play essential roles in
      osteosarcoma occurrence, invasion, and metastasis. This review summarizes the
      regulatory effect of circRNAs in the occurrence and development of osteosarcoma,
      concentrating on deregulation, regulatory mechanisms, and functions of circRNAs
      and their potential value as biomarkers and therapy.

PMID- 30282963
TI  - Treatment of Renal Fungal Ball with Fluconazole Instillation Through a
      Nephrostomy Tube: Case Report and Literature Review.
AB  - BACKGROUND Urinary tract candida infection can be due either to hematogenous
      dissemination of the organism or a retrograde infection. In debilitated or
      immunosuppressed septic patients, who have upper urinary tract obstruction with
      renal filling defect, fungal infection should be considered. We report on a
      patient with sepsis and renal fungal ball who was treated with percutaneous
      nephrostomy and intravenous antifungal agent, but the patient did not respond so
      instillation of fluconazole through nephrostomy was given. CASE REPORT A 60-year
      old male patient with a known case of diabetes mellitus with refractory urine
      retention underwent transurethral resection of the prostate. Postoperatively, the
      patient developed recurrent high-grade fever with left loin pain, and elevated
      septic parameters; urine and blood culture were positive for Candida albicans.
      Computed tomography urography showed left hydronephrosis with filling defect in
      the left renal pelvis with suspected renal fungal ball. Left percutaneous
      nephrostomy was performed and intravenous fluconazole started but the fever did
      not subside, therefore, the treatment was changed to anidulafungin. The patient
      improved but urine from both the bladder and the nephrostomy remained positive
      for candida. Instillation of fluconazole at 300 mg in 500 mL normal saline was
      applied through the nephrostomy tube over 12 hours at 40 mL/hour for 7 days.
      CONCLUSIONS Renal fungal ball is rare but can be serious, especially in
      immunocompromised patients. Management options for renal fungal ball include
      intravenous antifungal agents and percutaneous nephrostomy with antifungal
      instillation of antifungal agents. The objective of this case report was to
      document treatment success with the use of fluconazole instillation through a
      nephrostomy tube.

PMID- 30282964
TI  - Transient receptor potential channel 6 knockdown prevents apoptosis of renal
      tubular epithelial cells upon oxidative stress via autophagy activation.
AB  - Reactive oxygen species (ROS) are generated under various pathological conditions
      such as renal ischemia/reperfusion (I/R) injury and provoke damage to multiple
      cellular organelles and processes. Overproduction of ROS causes oxidative stress
      and contributes to damages of renal proximal tubular cells (PTC), which are the
      main cause of the pathogenesis of renal I/R injury. Autophagy is a dynamic
      process that removes long-lived proteins and damaged organelles via lysosome
      mediated degradation, which has an antioxidant effect that relieves oxidative
      stress. The canonical transient receptor potential channel 6 (TRPC6), a
      nonselective cation channel that allows passage of Ca2+, plays an important role
      in renal disease. Yet, the relationship between TRPC6 and autophagy, as well as
      their functions in renal oxidative stress injury, remains unclear. In this study,
      we found that oxidative stress triggered TRPC6-dependent Ca2+ influx in PTC to
      inhibit autophagy, thereby rendering cells more susceptible to death. We also
      demonstrated that TRPC6 knockout (TRPC6-/-) or inhibition by SAR7334, a TRPC6
      selective inhibitor, increased autophagic flux and mitigated oxidative stress
      induced apoptosis of PTC. The protective effects of TRPC6 ablation were prevented
      by autophagy inhibitors Chloroquine and Bafilomycin A1. Moreover, this study also
      shows that TRPC6 blockage promotes autophagic flux via inhibiting the
      PI3K/Akt/mTOR and ERK1/2 signaling pathways. This is the first evidence showing
      that TRPC6-mediated Ca2+ influx plays a novel role in suppressing cytoprotective
      autophagy triggered by oxidative stress in PTC, and it may become a novel
      therapeutic target for the treatment of renal oxidative stress injury in the
      future.

PMID- 30282965
TI  - Reduction of HIP2 expression causes motor function impairment and increased
      vulnerability to dopaminergic degeneration in Parkinson's disease models.
AB  - Huntingtin interaction protein 2 (HIP2) is an E2 ubiquitin-conjugating enzyme
      associated with neurodegenerative diseases, and HIP2 mRNA has been implicated as
      a potential blood biomarker for Parkinson's disease (PD). However, it is unclear
      whether the alteration of HIP2 expression may contribute to the development of
      PD, and whether the change of HIP2 in blood could reflect its expression in the
      brain or motor functions in PD patients. In this study, we established a mouse
      line with HIP2 haploinsufficiency. The reduction of the HIP2 expression led to
      spontaneous motor function impairment and dopaminergic neuronal loss.
      Furthermore, HIP2 haploinsufficiency increased the susceptibility of mice to 6
      hydroxydopamine (6-OHDA) and caused severe loss of dopaminergic neurons.
      Interestingly, in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse
      model for PD, we observed concurrent, highly correlated decrease of HIP2
      expression in the brain and in the blood. Using blood samples from more than 300
      patients, we validated the decreased HIP2 mRNA in PD patients, including de novo
      patients. Finally, in a 1-year, 20-patient study, we observed reversed blood HIP2
      mRNA levels accompanying improved motor and overall daily functions in 75% of the
      PD patients with instructed Tai Chi training. Therefore, our in vivo studies have
      indicated HIP2 insufficiency as a contributing factor for PD, and functionally
      validated blood HIP2 as a useful and reversible biomarker for PD.

PMID- 30282966
TI  - Novel engineered, membrane-localized variants of vascular endothelial growth
      factor (VEGF) protect retinal ganglion cells: a proof-of-concept study.
AB  - Endogenous vascular endothelial growth factor (VEGF-A) can protect retinal
      ganglion cells (RGC) from stress-induced cell death in ocular hypertensive
      glaucoma. To exploit the neuroprotective function of VEGF-A for therapeutic
      application in ocular disorders such as glaucoma while minimizing unwanted
      vascular side effects, we engineered two novel VEGF variants, eVEGF-38 and eVEGF
      53. These variants of the diffusible VEGF-A isoform VEGF121 are expressed as
      dimeric concatamers and remain tethered to the cell membrane, thus restricting
      the effects of the engineered VEGF to the cells expressing the protein. For
      comparison, we tested a Myc-tagged version of VEGF189, an isoform that binds
      tightly to the extracellular matrix and heparan sulfate proteoglycans at the cell
      surface, supporting only autocrine and localized juxtacrine signaling. In human
      retinal endothelial cells (hREC), expression of eVEGF-38, eVEGF-53, or VEGF189
      increased VEGFR2 phosphorylation without increasing expression of pro
      inflammatory markers, relative to VEGF165 protein and vector controls. AAV2
      mediated transduction of eVEGF-38, eVEGF-53, or VEGF189 into primary mouse RGC
      promoted synaptogenesis and increased the average total length of neurites and
      axons per RGC by ~ 12-fold, an increase that was mediated by VEGFR2 and PI3K/AKT
      signaling. Expression of eVEGF-38 in primary RGC enhanced expression of genes
      associated with neuritogenesis, axon outgrowth, axon guidance, and cell survival.
      Transduction of primary RGC with any of the membrane-associated VEGF constructs
      increased survival both under normal culture conditions and in the presence of
      the cytotoxic chemicals H2O2 (via VEGFR2/PI3K/AKT signaling) and N-methyl-D
      aspartate (via reduced Ca2+ influx). Moreover, RGC number was increased in mouse
      embryonic stem cell-derived retinal organoid cultures transduced with the eVEGF
      53 construct. The novel, engineered VEGF variants eVEGF-38 and eVEGF-53 show
      promise as potential therapeutics for retinal RGC neuroprotection when delivered
      using a gene therapy approach.

PMID- 30282968
TI  - Author Correction: The identification of carbon dioxide mediated protein post
      translational modifications.
AB  - The original version of this Article omitted the following from the
      Acknowledgements: 'This work was support by EPSRC grant EP/K504336/1 and
      Leverhulme Trust grant RPG-2016-017.' This has been corrected in both the PDF and
      HTML versions of the Article.

PMID- 30282967
TI  - Hydroxypropyl-beta and -gamma cyclodextrins rescue cholesterol accumulation in
      Niemann-Pick C1 mutant cell via lysosome-associated membrane protein 1.
AB  - Niemann-Pick type C (NPC) disease is a fatal hereditary neurodegenerative
      disorder characterized by a massive accumulation of cholesterol in lysosomes and
      late endosomes due to a defect in intracellular cholesterol trafficking.
      Dysfunction in intracellular cholesterol trafficking is responsible for about 50
      rare inherited lysosomal storage disorders including NPC. The lysosomal proteins
      NPC1 and NPC2 play a crucial role in trafficking of cholesterol from late
      endosomes and lysosomes to other cellular compartments. However, the detailed
      mechanisms of cholesterol trafficking at the late endosomes/lysosomes (LE/LY) are
      poorly understood. Studies showed that 2-hydroxypropyl-beta-cyclodextrin
      (HPbetaCD) alleviates the cholesterol accumulation defect in animal model and has
      been approved for a phase 2b/3 clinical trial for NPC. HPbetaCD is known to bind
      cholesterol; however, the mechanisms how HPbetaCD mediates the exit of
      cholesterol from the LE/LY compartments are still unknown. Further, another
      cyclodextrin (CD) derivative, 2-hydroxypropyl-gamma-cyclodextrin (HPgammaCD), was
      shown to reduce intracellular cholesterol accumulation in NPC patient cells and
      NPC mice model. Herein, we identified a number of candidate proteins
      differentially expressed in NPC patient-derived cells compared to cells derived
      from a healthy donor using a proteomic approach. Interestingly, both HPbetaCD and
      HPgammaCD treatments modulated the expression of most of these NPC-specific
      proteins. Data showed that treatment with both CDs induces the expression of the
      lysosome-associated membrane protein 1 (LAMP-1) in NPC patient-derived cells.
      Remarkably, LAMP-1 overexpression in HeLa cells rescued U18666A-induced
      cholesterol accumulation suggesting a role of LAMP-1 in cholesterol trafficking.
      We propose that HPbetaCD and HPgammaCD facilitate cholesterol export from the
      LE/LY compartments via the LAMP-1 protein, which may play a crucial role in
      cholesterol trafficking at the LE/LY compartments when there is no functional
      NPC1 protein. Together, this study uncovers new cellular mechanisms for
      cholesterol trafficking, which will contribute to development of novel
      therapeutic approaches for lysosomal storage diseases.

PMID- 30282969
TI  - BMSCs pre-treatment ameliorates inflammation-related tissue destruction in LPS
      induced rat DIC model.
AB  - This study aimed to investigate the effect of bone marrow-derived mesenchymal
      stem cells (BMSCs) on disseminated intravascular coagulation (DIC) model rats and
      to further explore the underlying mechanism. A rat model of lipopolysaccharide
      (LPS)-induced DIC was successfully established, as indicated by impaired plasma
      hemostatic parameters and damaged organ functions in rats. Importantly, pre
      treatment with rat allogeneic BMSCs before LPS injection significantly alleviated
      systemic intravascular coagulation, reduced plasma levels of organ dysfunction
      indicators and pro-inflammatory cytokines, suppressed fibrin microthrombi
      formation, ameliorated liver, heart, and renal injuries, and increased 24-hour
      survival rates in LPS-induced DIC rats. The protection of BMSCs against DIC was
      in a moderately dose-dependent manner. Further investigation revealed that BMSCs
      co-cultured with peripheral blood mononuclear cells (PBMCs) significantly
      inhibited the LPS-stimulated PBMCs proliferation and the release of pro
      inflammatory cytokines from PBMCs. Of note, upregulation of immunosuppressive
      factors including indoleamine 2,3-dioxygenase and interleukin-10, which was
      induced by interferon-gamma, contributed to BMSCs-mediated inhibition of LPS
      stimulated PBMCs proliferation. These effects do not depend on the direct cell
      cell contact. In conclusion, BMSCs pre-treatment ameliorates inflammation-related
      tissue destruction in LPS-induced DIC model rats. The protection of BMSCs may be
      attributed to their anti-inflammatory and immunomodulatory properties, which
      render BMSCs a promising source for stem cell-based therapeutic approaches in
      inflammation-related DIC.

PMID- 30282971
TI  - High-content ductile coherent nanoprecipitates achieve ultrastrong high-entropy
      alloys.
AB  - Precipitation-hardening high-entropy alloys (PH-HEAs) with good strength
      ductility balances are a promising candidate for advanced structural
      applications. However, current HEAs emphasize near-equiatomic initial
      compositions, which limit the increase of intermetallic precipitates that are
      closely related to the alloy strength. Here we present a strategy to design
      ultrastrong HEAs with high-content nanoprecipitates by phase separation, which
      can generate a near-equiatomic matrix in situ while forming strengthening phases,
      producing a PH-HEA regardless of the initial atomic ratio. Accordingly, we
      develop a non-equiatomic alloy that utilizes spinodal decomposition to create a
      low-misfit coherent nanostructure combining a near-equiatomic disordered face
      centered-cubic (FCC) matrix with high-content ductile Ni3Al-type ordered
      nanoprecipitates. We find that this spinodal order-disorder nanostructure
      contributes to a strength increase of ~1.5 GPa (>560%) relative to the HEA
      without precipitation, achieving one of the highest tensile strength (1.9 GPa)
      among all bulk HEAs reported previously while retaining good ductility (>9%).

PMID- 30282972
TI  - LncRNA-MEG3 inhibits activation of hepatic stellate cells through SMO protein and
      miR-212.
AB  - Activation of hepatic stellate cells (HSCs), a pivotal event in liver fibrosis,
      is considered as an epithelial-mesenchymal transition (EMT) process. Deregulation
      of long noncoding RNAs (lncRNAs) has been reported to be involved in a series of
      human diseases. LncRNA-maternally expressed gene 3 (MEG3) functions as a tumor
      suppressor in cancers and has been shown to play a vital role in EMT process.
      However, the biological role of MEG3 in liver fibrosis is largely unknown. In
      this study, MEG3 was reduced in vivo and in vitro during liver fibrosis.
      Restoring of MEG3 expression led to the suppression of liver fibrosis, with a
      reduction in alpha-SMA and type I collagen. Notably, MEG3 overexpression
      inhibited HSC activation through EMT, associated with an increase in epithelial
      markers and a reduction in mesenchymal markers. Further studies showed that
      Hedgehog (Hh) pathway-mediated EMT process was involved in the effects of MEG3 on
      HSC activation. Smoothened (SMO) is a member of Hh pathway. Using bioinformatic
      analysis, an interaction between MEG3 and SMO protein was predicted. This
      interaction was confirmed by the results of RNA immunoprecipitation and deletion
      mapping analysis. Furthermore, MEG3 was confirmed as a target of microRNA-212
      (miR-212). miR-212 was partly responsible for the effects of MEG3 on EMT process.
      Interestingly, MEG3 was also reduced in chronic hepatitis B (CHB) patients with
      liver fibrosis when compared with healthy controls. MEG3 negatively correlated
      with fibrosis stage in CHB patients. In conclusion, we demonstrate that MEG3
      inhibits Hh-mediated EMT process in liver fibrosis via SMO protein and miR-212.

PMID- 30282970
TI  - Diagnosis and treatment of schizotypal personality disorder: evidence from a
      systematic review.
AB  - The main objective of this review was to evaluate studies on the diagnosis,
      treatment, and course of schizotypal personality disorder and to provide a
      clinical guidance on the basis of that evaluation. A systematic search in the
      PubMed/MEDLINE databases was conducted. Two independent reviewers extracted and
      assessed the quality of the data. A total of 54 studies were eligible for
      inclusion: 18 were on diagnostic instruments; 22, on pharmacological treatment;
      3, on psychotherapy; and 13, on the longitudinal course of the disease. We
      identified several suitable and reliable questionnaires for screening (PDQ-4+ and
      SPQ) and diagnosing (SIDP, SIDP-R, and SCID-II) schizotypal personality disorder.
      Second-generation antipsychotics (mainly risperidone) were the most often studied
      drug class and were described as beneficial. Studies on the longitudinal course
      described a moderate remission rate and possible conversion rates to other
      schizophrenia spectrum disorders. Because of the heterogeneity of the studies and
      the small sample sizes, it is not yet possible to make evidence-based
      recommendations for treatment. This is a systematic evaluation of diagnostic
      instruments and treatment studies in schizotypal personality disorder. We
      conclude that there is currently only limited evidence on which to base treatment
      decisions in this disorder. Larger interventional trials are needed to provide
      the data for evidence-based recommendations.

PMID- 30282973
TI  - Exosomal 15-LO2 mediates hypoxia-induced pulmonary artery hypertension in vivo
      and in vitro.
AB  - Our previous studies have shown that 15-LO2/15-HETE induced by hypoxia played an
      important role in pulmonary arterial hypertension (PH). However, the
      transportations of 15-LO2/15-HETE among the cells remain elusive. In this study,
      we investigated the specific involvement of 15-LO2-containing exosomes in the
      overproliferation of pulmonary artery endothelial cells (PAECs) induced by
      hypoxia and the underlying mechanism. In vitro, 15-LO2 was abundantly expressed
      and enriched in exosomes secreted from hypoxic PAECs, which subsequently
      activated the STAT3 signaling pathway, resulting in a robust increase in PAECs
      proliferation. In vivo treatment with the exosomes inhibitor GW4869 protected the
      pulmonary vascular homeostasis from dysfunctional and abnormal remodeling.
      Moreover, 15-LO2 was ubiquitinated under hypoxia, and further inhibition of the
      ubiquitin-proteasome system significantly suppressed PAECs proliferation,
      suggesting that ubiquitination of 15-LO2 may contribute to its sorting into
      exosomes. Overall, these findings indicate a previously unrecognized effect of
      exosomes and the cargo 15-LO2 in pulmonary vascular homeostasis on the
      pathogenesis of PH.

PMID- 30282974
TI  - The use of natural media amendments to produce kale enhanced with functional
      lipids in controlled environment production system.
AB  - Diets high in vegetable consumption is highly correlated with reduced risk of
      developing common lifestyle related diseases. We investigated the effects of
      three natural growth media amendments [potassium humate, dry vermicast, volcanic
      minerals or Promix alone (Control)] in enhancing the accumulation of functional
      lipids in greenhouse grown kale. Functional lipids (n9, n6, n3 fatty acids,
      diglycerides, galactolipids and phytosterols) were assessed using either gas
      chromatography/mass spectrometry (GC/MS) or ultra-high performance liquid
      chromatography-high resolution tandem mass spectrometry (UHPLC-HRMS/MS). The
      results showed volcanic minerals and dry vermicast were the most successful in
      enhancing the accumulation of functional lipids in kale. For example, dry
      vermicast enhanced the accumulation of total C18:1n9 and C16:3n3 fatty acids,
      while total C18:2n6 fatty acid accumulation was enhanced by volcanic minerals. In
      conclusion, natural growing medium amendments are remarkably effective in
      modulating the accumulation of functional lipids in kale grown under controlled
      environment conditions. This could be a useful strategy for functional foods
      production in control environment production systems. Increase access to kale
      with enhanced functional lipids could aid in increase consumption of these health
      promotive compounds in the diet with potential implications in population health.

PMID- 30282976
TI  - The effect of pulsed current on the shear deformation behavior of Ti-6Al-4V
      alloy.
AB  - Pulse current-assisted forming is a new technology to improve the plastic
      deformability of titanium alloy. In this work, Shearing tests of Ti-6Al-4V alloy
      were conducted using hat-shaped specimens under pulsed current (electroplastic
      shearing) and constant temperature (isothermal shearing). The actual deformation
      in shear zone of electroplastic shearing was larger than that of isothermal
      shearing. The shear load is also decreased by the pulsed current. Microstructure
      variation in the shear zone was investigated by scanning electron microscopy. An
      evident straight shear band was observed in the electroplastic shearing
      specimens. The deformation model of shear zone was established. Intracrystalline
      deformation was markedly easier for the grains with the pulsed current and
      induced larger deformation of the grains along the shear direction. Microcracks
      were observed in the shear zone of isothermal shearing, but none were found in
      the shear zone of electroplastic shearing. Evident crack healing was found in the
      crack tip of the shear zone of electroplastic shearing.

PMID- 30282975
TI  - Patients with Chronic Obstructive Pulmonary Disease harbour a variation of
      Haemophilus species.
AB  - H. haemolyticus is often misidentified as NTHi due to their close phylogenetic
      relationship. Differentiating between the two is important for correct
      identification and appropriate treatment of infective organism and to ensure any
      role of H. haemolyticus in disease is not being overlooked. Speciation however is
      not completely reliable by culture and PCR methods due to the loss of haemolysis
      by H. haemolyticus and the heterogeneity of NTHi. Haemophilus isolates from COPD
      as part of the AERIS study (ClinicalTrials - NCT01360398) were speciated by
      analysing sequence data for the presence of molecular markers. Further
      investigation into the genomic relationship was carried out using average
      nucleotide identity and phylogeny of allelic and genome alignments. Only 6.3%
      were identified as H. haemolyticus. Multiple in silico methods were able to
      distinguish H. haemolyticus from NTHi. However, no single gene target was found
      to be 100% accurate. A group of omp2 negative NTHi were observed to be
      phylogenetically divergent from H. haemolyticus and remaining NTHi. The presence
      of an atypical group from a geographically and disease limited set of isolates
      supports the theory that the heterogeneity of NTHi may provide a genetic
      continuum between NTHi and H. haemolyticus.

PMID- 30282977
TI  - Nuclear expansion and pore opening are instant signs of neuronal hypoxia and can
      identify poorly fixed brains.
AB  - The initial phase of neuronal death is not well characterized. Here, we show that
      expansion of the nuclear membrane without losing its integrity along with
      peripheralization of chromatin are immediate signs of neuronal injury.
      Importantly, these changes can be identified with commonly used nuclear stains
      and used as markers of poor perfusion-fixation. Although frozen sections are
      widely used, no markers are available to ensure that the observed changes were
      not confounded by perfusion-induced hypoxia/ischemia. Moreover, HMGB1 was
      immediately released and p53 translocated to mitochondria in hypoxic/ischemic
      neurons, whereas nuclear pore complex inhibitors prevented the nuclear changes,
      identifying novel neuroprotection targets.

PMID- 30282978
TI  - Coherently driven microcavity-polaritons and the question of superfluidity.
AB  - Due to their driven-dissipative nature, photonic quantum fluids present new
      challenges in understanding superfluidity. Some associated effects have been
      observed, and notably the report of nearly dissipationless flow for coherently
      driven microcavity-polaritons was taken as a smoking gun for superflow. Here, we
      show that the superfluid response-the difference between responses to
      longitudinal and transverse forces-is zero for coherently driven polaritons. This
      is a consequence of the gapped excitation spectrum caused by external phase
      locking. Furthermore, while a normal component exists at finite pump momentum,
      the remainder forms a rigid state that is unresponsive to either longitudinal or
      transverse perturbations. Interestingly, the total response almost vanishes when
      the real part of the excitation spectrum has a linear dispersion, which was the
      regime investigated experimentally. This suggests that the observed suppression
      of scattering should be interpreted as a sign of this new rigid state and not a
      superfluid.

PMID- 30282979
TI  - CLIC1 and CLIC4 complement CA125 as a diagnostic biomarker panel for all subtypes
      of epithelial ovarian cancer.
AB  - New plasma and tissue biomarkers of epithelial ovarian cancer (EOC) could improve
      early diagnosis and post-diagnosis clinical management. Here we investigated
      tissue staining and tissue secretion of CLIC1 and CLIC4 across EOC subtypes.
      CLIC1 and CLIC4 are two promising biomarkers we previously showed were elevated
      in EOC patient sera. Individually, CLIC1 or CLIC4 stained larger percentages of
      malignant tumors across all EOC subtypes compared with CA125, particularly early
      stage and mucinous tumors. CLIC4 also stained benign tumors but staining was
      limited to nuclei; whereas malignant tumors showed diffuse cellular staining of
      stromal and tumor cells. Both proteins were shed by all EOC subtypes tumors in
      short term organ culture at more consistent levels than CA125, supporting their
      potential as pan-subtype serum and tissue biomarkers. Elevated CLIC4 expression,
      but not CLIC1 expression, was a negative indicator of patient survival, and CLIC4
      knockdown in cultured cells decreased cell proliferation and migration indicating
      a potential role in tumor progression. These results suggest CLIC1 and CLIC4 are
      promising serum and tissue biomarkers as well as potential therapeutic targets
      for all EOC subtypes. This justifies development of high throughput serum/plasma
      biomarker assays to evaluate utility of a biomarker panel consisting of CLIC1,
      CLIC4 and CA125.

PMID- 30282981
TI  - Mucociliary Clearance in Mice Measured by Tracking Trans-tracheal Fluorescence of
      Nasally Aerosolized Beads.
AB  - Mucociliary clearance (MCC) is the first line of defense in clearing airways. In
      genetically engineered mice, each component of this system (ciliary beat, mucus,
      airway surface hydration) can be studied separately to determine its contribution
      to MCC. Because MCC is difficult to measure in mice, MCC measurements are often
      omitted from these studies. We report a simple method to measure MCC in mice
      involving nasal inhalation of aerosolized fluorescent beads and trans-tracheal
      bead tracking. This method has a number of advantages over existing methods: (1)
      a small volume of liquid is deposited thus minimally disturbing the airway
      surface; (2) bead behavior on airways can be visualized; (3) useful for adult or
      neonatal mice; (4) the equipment is relatively inexpensive and easily obtainable.
      The type of anesthetic had no significant effect on the rate of MCC, but
      overloading the airways with beads significantly decreased MCC. In addition, the
      rate of bead transport was not different in alive (3.11 mm/min) vs recently
      euthanized mice (3.10 mm/min). A 5-min aerosolization of beads in a solution
      containing UTP significantly increased the rate of MCC, demonstrating that our
      method would be of value in testing the role of various pharmacological agents on
      MCC.

PMID- 30282980
TI  - Suppression of SUN2 by DNA methylation is associated with HSCs activation and
      hepatic fibrosis.
AB  - Hepatic myofibroblasts, activated hepatic stellate cells (HSCs), are the main
      cell type of extracellular matrix (ECM) deposition during hepatic fibrosis.
      Aberrant DNA methylation-regulated HSCs activation in liver fibrogenesis has been
      reported, but the functional roles and mechanisms of DNA methylation in hepatic
      fibrosis remain to be elucidated. In the present study, reduced representation
      bisulfite sequencing (RRBS) analysis of primary HSCs revealed hypermethylation
      patterns in hepatic fibrosis. Interestingly, we found SAD1/UNC84 domain protein-2
      (SUN2) gene hypermethylation at CpG sites during liver fibrogenesis in mice with
      CCl4-induced hepatic fibrosis, which was accompanied by low expression of SUN2.
      In vivo overexpression of SUN2 following adeno-associated virus-9 (AAV9)
      administration inhibited CCl4-induced liver injury and reduced fibrogenesis
      marker expression. Consistently, in vitro experiments showed that enforced
      expression of SUN2 suppressed HSCs activation and exerted anti-fibrogenesis
      effects in TGF-beta1-activated HSC-T6 cells. In addition, the signaling
      mechanisms related to SUN2 expression were investigated in vivo and in vitro.
      Methyltransferase-3b (DNMT3b) is the principal regulator of SUN2 expression.
      Mechanistically, inhibition of protein kinase B (AKT) phosphorylation may be a
      crucial pathway for SUN2-mediated HSCs activation. In conclusion, these findings
      provide substantial new insights into SUN2 in hepatic fibrosis.

PMID- 30282982
TI  - Quasicrystal nucleation and [Formula: see text] module twin growth in an
      intermetallic glass-forming system.
AB  - While quasicrystals possess long-range orientational order they lack translation
      periodicity. Considerable advancements in the elucidation of their structures and
      formative principles contrast with comparatively uncharted interrelations, as
      studies bridging the spatial scales from atoms to the macroscale are scarce.
      Here, we report on the homogeneous nucleation of a single quasicrystalline seed
      from the undercooled melt of glass-forming NiZr and its continuous growth into a
      tenfold twinned dendritic microstructure. Observing a series of crystallization
      events on electrostatically levitated NiZr confirms homogeneous nucleation.
      Mapping the microstructure with electron backscatter diffraction suggests a
      unique, distortion-free structure merging a common structure type of binary
      alloys with a spiral growth mechanism resembling phyllotaxis. A general geometric
      description, relating all atomic loci, observed by atomic resolution electron
      microscopy, to a pentagonal [Formula: see text] module, explains how the seed's
      decagonal long-range orientational order is conserved throughout the symmetry
      breaking steps of twinning and dendritic growth.

PMID- 30282983
TI  - CPP-Ts: a new intracellular calcium channel modulator and a promising tool for
      drug delivery in cancer cells.
AB  - Scorpion sting envenoming impacts millions of people worldwide, with cardiac
      effects being one of the main causes of death on victims. Here we describe the
      first Ca2+ channel toxin present in Tityus serrulatus (Ts) venom, a cell
      penetrating peptide (CPP) named CPP-Ts. We show that CPP-Ts increases
      intracellular Ca2+ release through the activation of nuclear InsP3R of
      cardiomyocytes, thereby causing an increase in the contraction frequency of these
      cells. Besides proposing a novel subfamily of Ca2+ active toxins, we investigated
      its potential use as a drug delivery system targeting cancer cell nucleus using
      CPP-Ts's nuclear-targeting property. To this end, we prepared a synthetic CPP-Ts
      sub peptide14-39 lacking pharmacological activity which was directed to the
      nucleus of specific cancer cell lines. This research identifies a novel subfamily
      of Ca2+ active toxins and provides new insights into biotechnological
      applications of animal venoms.

PMID- 30282984
TI  - A toolbox for multiplexed super-resolution imaging of the E. coli nucleoid and
      membrane using novel PAINT labels.
AB  - Maintenance of the bacterial homeostasis initially emanates from interactions
      between proteins and the bacterial nucleoid. Investigating their spatial
      correlation requires high spatial resolution, especially in tiny, highly confined
      and crowded bacterial cells. Here, we present super-resolution microscopy using a
      palette of fluorescent labels that bind transiently to either the membrane or the
      nucleoid of fixed E. coli cells. The presented labels are easily applicable,
      versatile and allow long-term single-molecule super-resolution imaging
      independent of photobleaching. The different spectral properties allow for
      multiplexed imaging in combination with other localisation-based super-resolution
      imaging techniques. As examples for applications, we demonstrate correlated super
      resolution imaging of the bacterial nucleoid with the position of genetic loci,
      of nascent DNA in correlation to the entire nucleoid, and of the nucleoid of
      metabolically arrested cells. We furthermore show that DNA- and membrane
      targeting labels can be combined with photoactivatable fluorescent proteins and
      visualise the nano-scale distribution of RNA polymerase relative to the nucleoid
      in drug-treated E. coli cells.

PMID- 30282985
TI  - Human serum albumin alters specific genes that can play a role in survival and
      persistence in Acinetobacter baumannii.
AB  - In the past few decades Acinetobacter baumannii has emerged as a notorious
      nosocomial pathogen because of its ability to acquire genetic material and
      persist in extreme environments. Recently, human serum albumin (HSA) was shown to
      significantly increase natural transformation frequency in A. baumannii. This
      observation led us to perform transcriptomic analysis of strain A118 under HSA
      induction to identify genes that are altered by HSA. Our results revealed the
      statistically significant differential expression of 296 protein-coding genes,
      including those associated with motility, biofilm formation, metabolism, efflux
      pumps, capsule synthesis, and transcriptional regulation. Phenotypic analysis of
      these traits showed an increase in surface-associated motility, a decrease in
      biofilm formation, reduced activity of a citric acid cycle associated enzyme, and
      increased survival associated with zinc availability. Furthermore, the expression
      of genes known to play a role in pathogenicity and antibiotic resistance were
      altered. These genes included those associated with RND-type efflux pumps, the
      type VI secretion system, iron acquisition/metabolism, and beta-lactam
      resistance. Together, these results illustrate how human products, in particular
      HSA, may play a significant role in both survival and persistence of A.
      baumannii.

PMID- 30282986
TI  - An ultra-low thiourea catalyzed strain-release glycosylation and a multicatalytic
      diversification strategy.
AB  - The utility of thiourea catalysis in selective glycosylation strategies has
      gained significant momentum lately due to its versatility in hydrogen bonding or
      anionic recognition activation modes. The use of these non-covalent interactions
      constitute a powerful means to construct glycosidic linkages as it mimics
      physiologically occurring glycosyltransferases. However, glycosyl donor
      activation through the currently employed catalysts is moderate such that, in
      general, catalyst loadings are rather high in these transformations. In addition,
      thiourea catalysis has not been well explored for the synthesis of furanosides.
      Herein, we demonstrate an ultra-low loadings stereoselective and stereospecific
      thiourea catalyzed strain-release furanosylation and pyranosylation strategy. Our
      ultra-low organocatalyzed furanosylation enables a multicatalytic strategy, which
      opens up a unique avenue towards rapid diversification of synthetic glycosides.
      In-situ NMR monitoring unravel insights into unknown reaction intermediates and
      initial rate kinetic studies reveal a plausible synergistic hydrogen
      bonding/Bronsted acid activation mode.

PMID- 30282988
TI  - Maternal high-fat diet consumption induces sex-dependent alterations of the
      endocannabinoid system and redox homeostasis in liver of adult rat offspring.
AB  - Maternal diet plays a critical role in health development. Perinatal
      overnutrition induces metabolic dysfunctions and obesity in the offspring.
      Obesity is associated with endocannabinoid system (ECS) over activation and
      oxidative stress. Liver ECS activation induces hepatic steatosis, inflammation
      and fibrosis while the antagonism of cannabinoid receptors ameliorates these
      alterations. Here, we investigated the effect of perinatal maternal high-fat diet
      (HF, 29% of calories as fat) on the ECS and antioxidant system in liver of male
      and female adult rat offspring (180 days old). Maternal HF diet increased hepatic
      cannabinoid receptors, ECS metabolizing enzymes and triglyceride content, with
      male offspring more affected. ECS changes are likely independent of estradiol
      serum levels but associated with increased hepatic content of estrogen receptor,
      which can stimulate the expression of ECS components. Differently, maternal HF
      diet decreased the activity of the antioxidant enzymes glutathione peroxidase,
      superoxide dismutase and catalase, and increased oxidative stress markers in both
      sexes. Alterations in the redox homeostasis were associated with mitochondria
      damage but not with liver fibrosis. Our data suggest that maternal HF diet
      induces ECS over activation in adulthood, and that male offspring are at higher
      risk to develop liver disease compared with female rats.

PMID- 30282987
TI  - Bi-directional cell-pericellular matrix interactions direct stem cell fate.
AB  - Modifiable hydrogels have revealed tremendous insight into how physical
      characteristics of cells' 3D environment drive stem cell lineage specification.
      However, in native tissues, cells do not passively receive signals from their
      niche. Instead they actively probe and modify their pericellular space to suit
      their needs, yet the dynamics of cells' reciprocal interactions with their
      pericellular environment when encapsulated within hydrogels remains relatively
      unexplored. Here, we show that human bone marrow stromal cells (hMSC)
      encapsulated within hyaluronic acid-based hydrogels modify their surroundings by
      synthesizing, secreting and arranging proteins pericellularly or by degrading the
      hydrogel. hMSC's interactions with this local environment have a role in
      regulating hMSC fate, with a secreted proteinaceous pericellular matrix
      associated with adipogenesis, and degradation with osteogenesis. Our observations
      suggest that hMSC participate in a bi-directional interplay between the
      properties of their 3D milieu and their own secreted pericellular matrix, and
      that this combination of interactions drives fate.

PMID- 30282989
TI  - Polymerization driven monomer passage through monolayer chemical vapour
      deposition graphene.
AB  - Mass transport through graphene is receiving increasing attention due to the
      potential for molecular sieving. Experimental studies are mostly limited to the
      translocation of protons, ions, and water molecules, and results for larger
      molecules through graphene are rare. Here, we perform controlled radical
      polymerization with surface-anchored self-assembled initiator monolayer in a
      monomer solution with single-layer graphene separating the initiator from the
      monomer. We demonstrate that neutral monomers are able to pass through the
      graphene (via native defects) and increase the graphene defects ratio (Raman
      ID/IG) from ca. 0.09 to 0.22. The translocations of anionic and cationic monomers
      through graphene are significantly slower due to chemical interactions of
      monomers with the graphene defects. Interestingly, if micropatterned initiator
      monolayers are used, the translocations of anionic monomers apparently cut the
      graphene sheet into congruent microscopic structures. The varied interactions
      between monomers and graphene defects are further investigated by quantum
      molecular dynamics simulations.

PMID- 30282991
TI  - Social and nutritional factors shape larval aggregation, foraging, and body mass
      in a polyphagous fly.
AB  - The majority of insect species have a clearly defined larval stage during
      development. Larval nutrition is crucial for individuals' growth and development,
      and larval foraging success often depends on both resource availability and
      competition for those resources. To date, however, little is known about how
      these factors interact to shape larval development and behaviour. Here we
      manipulated the density of larvae of the polyphagous fruit fly pest Bactrocera
      tryoni ('Queensland fruit fly'), and the diet concentration of patches in a
      foraging arena to address this gap. Using advanced statistical methods of machine
      learning and linear regression models, we showed that high larval density results
      in overall high larval aggregation across all diets except in extreme diet
      dilutions. Larval aggregation was positively associated with larval body mass
      across all diet concentrations except in extreme diet dilutions where this
      relationship was reversed. Over time, larvae in low-density arenas also tended to
      aggregate while those in high-density arenas tended to disperse, an effect that
      was observed for all diet concentrations. Furthermore, larvae in high-density
      arenas displayed significant avoidance of low concentration diets - a behaviour
      that was not observed amongst larvae in low-density arenas. Thus, aggregation can
      help, rather than hinder, larval growth in high-density environments, and larvae
      may be better able to explore available nutrition when at high-density than when
      at low-density.

PMID- 30282990
TI  - Surface-modified three-dimensional graphene nanosheets as a stationary phase for
      chromatographic separation of chiral drugs.
AB  - Carbon-based stationary phases for chromatographic separation have been
      commercially available since the 1980s. Porous graphitic carbon liquid
      chromatography columns are known to be highly resistant to aggressive mobile
      phases and extreme pH values of solvents and eluents, an important advantage
      compared to conventional silica-based alternatives. In our work, we demonstrate a
      new variant of carbon-based stationary phases for liquid chromatography,
      specifically developed for chiral separation. Mesoporous three-dimensional
      graphene nanosheets (3D GNS), functionalized with tetracyanoethylene oxide
      (TCNEO) and (S)-(+)-2-pyrrolidinemethanol, demonstrate pharmaceutical-grade
      chiral separation of model ibuprofen and thalidomide racemic mixtures when used
      as Chiral Stationary Phases (CSPs), with performance parameters comparable to
      currently commercially available CSPs. Simple covalent attachment of
      functionalization groups to the surface of mesoporous three-dimensional graphene
      nanosheets makes these carbon-based CSPs chemically stable and up to an order of
      magnitude less expensive than standard silica-based analogues.

PMID- 30282992
TI  - Rich spatio-temporal stimulus dynamics unveil sensory specialization in cortical
      area S2.
AB  - Tactile perception in rodents depends on simultaneous, multi-whisker contacts
      with objects. Although it is known that neurons in secondary somatosensory cortex
      (wS2) respond to individual deflections of many whiskers, wS2's precise function
      remains unknown. The convergence of information from multiple whiskers into wS2
      neurons suggests that they are good candidates for integrating multi-whisker
      information. Here, we apply stimulation patterns with rich dynamics
      simultaneously to 24 macro-vibrissae of rats while recording large populations of
      single neurons. Varying inter-whisker correlations without changing single
      whisker statistics, we observe pronounced supra-linear multi-whisker integration.
      Using novel analysis methods, we show that continuous multi-whisker movements
      contribute to the firing of wS2 neurons over long temporal windows, facilitating
      spatio-temporal integration. In contrast, primary cortex (wS1) neurons encode
      fine features of whisker movements on precise temporal scales. These results
      provide the first description of wS2's representation during multi-whisker
      stimulation and outline its specialized role in parallel to wS1 tactile
      processing.

PMID- 30282994
TI  - Ecto-Calreticulin is essential for an efficient immunogenic cell death
      stimulation in mouse melanoma.
AB  - Skin melanoma remains one of the most aggressive and difficult to treat human
      malignancy, with an increasing incidence every year. Although surgical resection
      represents the best therapeutic approach, this is only feasible in cases of early
      diagnosis. Furthermore, the established malignancy is resistant to all
      therapeutic strategies employed so far, resulting in an unacceptable patient
      survival rate. Although the immune-mediated therapeutic approaches, based on anti
      PD1 or anti-CTLA4, are very promising and under clinical trial experimentation,
      they could conceal not yet fully emerged pitfalls such as the development of
      autoimmune diseases. Therefore, alternative therapeutic approaches are still
      under investigation, such as the immunogenic cell death (ICD) process. Here we
      show that the lack of calreticulin translocation onto mouse melanoma cell
      membrane prevents the stimulation of an effective ICD response in vivo.

PMID- 30282993
TI  - Cloning of the wheat Yr15 resistance gene sheds light on the plant tandem kinase
      pseudokinase family.
AB  - Yellow rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a
      devastating fungal disease threatening much of global wheat production. Race
      specific resistance (R)-genes are used to control rust diseases, but the rapid
      emergence of virulent Pst races has prompted the search for a more durable
      resistance. Here, we report the cloning of Yr15, a broad-spectrum R-gene derived
      from wild emmer wheat, which encodes a putative kinase-pseudokinase protein,
      designated as wheat tandem kinase 1, comprising a unique R-gene structure in
      wheat. The existence of a similar gene architecture in 92 putative proteins
      across the plant kingdom, including the barley RPG1 and a candidate for Ug8,
      suggests that they are members of a distinct family of plant proteins, termed
      here tandem kinase-pseudokinases (TKPs). The presence of kinase-pseudokinase
      structure in both plant TKPs and the animal Janus kinases sheds light on the
      molecular evolution of immune responses across these two kingdoms.

PMID- 30282995
TI  - Novel millimeter-wave-based method for in situ cell isolation and other
      applications.
AB  - As an alternative to laser-based methods, we developed a novel in situ cell
      isolation method and instrument based on local water absorption of millimeter
      wave (MMW) radiation that occurs in cellular material and nearby culture medium
      while the cultureware materials (plastic and glass) are transparent to MMW
      frequencies. Unwanted cells within cell population are targeted with MMWs in
      order to kill them by overheating. The instrument rapidly (within 2-3 seconds)
      heats a cell culture area of about 500 um in diameter to 50  degrees C using a
      low-power W-band (94 GHz) MMW source. Heated cells in the area detach from the
      substrate and can be removed by a media change leaving a bare spot. Hence we
      named the instrument "CellEraser". Quick, local and non-contact heating with
      sharp boundaries of the heated area allows elimination of the unwanted cells
      without affecting the neighboring cells. The instrument is implemented as a
      compact microscope attachment and the selective hyperthermic treatment can be
      done manually or in an automated mode. Mammalian cells heated even momentarily
      above 50  degrees C will not survive. This "temperature of no return" does not
      compromise cellular membranes nor does it denature proteins. Using the CellEraser
      instrument we found that the key event that determines the fate of a cell at
      elevated temperatures is whether or not the selectivity of its nucleus is
      compromised. If a cell nucleus becomes "leaky" allowing normally excluded
      (cytoplasmic) proteins in and normally nuclear-localized proteins out, that cell
      is destined to die. Quick heating by MMWs to higher temperatures (70  degrees C)
      denatures cellular proteins but the cells are not able to detach from the
      substrate - instead they undergo a phenomenon we called "thermofixation": such
      cells look similar to cells fixed with common chemical fixatives. They remain
      flat and are not washable from the substrate. Interestingly, their membranes
      become permeable to DNA dyes and even to antibodies. Thermofixation allows the
      use of western blot antibodies for immunofluorescence imaging.

PMID- 30282996
TI  - Long noncoding RNA MEG3 regulates LATS2 by promoting the ubiquitination of EZH2
      and inhibits proliferation and invasion in gallbladder cancer.
AB  - Gallbladder cancer (GBC) is the most common type of biliary tract cancer
      worldwide. Long noncoding RNAs (lncRNAs) play essential roles in physiological
      and pathological development. LncRNA MEG3, a tumor suppressor, has been reported
      to play important roles in some cancers, but the role of MEG3 in GBC remains
      largely unknown. The purpose of the present study was to explore the role of MEG3
      in proliferation and invasion and the potential molecular mechanism in GBC. We
      found that MEG3 was downregulated in GBC tissues and cells, and low expression of
      MEG3 was correlated with poor prognostic outcomes in patients. Overexpression of
      MEG3 inhibited GBC cell proliferation and invasion, induced cell apoptosis and
      decreased tumorigenicity in nude mice. Moreover, we found that MEG3 was
      associated with EZH2 and attenuated EZH2 by promoting its ubiquitination.
      Furthermore, MEG3 executed its functions via EZH2 to regulate the downstream
      target gene LATS2. Taken together, these findings suggest that MEG3 is an
      effective target for GBC therapy and may facilitate the development of lncRNA
      directed diagnostics and therapeutics against GBC.

PMID- 30282997
TI  - Inhibition of the gyrA promoter by transcription-coupled DNA supercoiling in
      Escherichia coli.
AB  - The E. coli gyrA promoter (PgyrA) is a DNA supercoiling sensitive promoter,
      stimulated by relaxation of DNA templates, and inhibited by (-) DNA supercoiling
      in bacteria. However, whether PgyrA can be inhibited by transient and localized
      transcription-coupled DNA supercoiling (TCDS) has not been fully examined. In
      this paper, using different DNA templates including the E. coli chromosome, we
      show that transient and localized TCDS strongly inhibits PgyrA in E. coli. This
      result can be explained by a twin-supercoiled domain model of transcription in
      which (+) and (-) supercoiled domains are generated around the transcribing RNA
      polymerase. We also find that fluoroquinolones, such as ciprofloxacin, can
      substantially increase the expression of the firefly luciferase under the control
      of the PgyrA coupled to a divergent IPTG-inducible promoter in the presence of
      IPTG. This stimulation of PgyrA by fluoroquinolones can be also explained by the
      twin-supercoiled domain model of transcription. This unique property of TCDS may
      be configured into a high throughput-screening (HTS) assay to identify
      antimicrobial compounds targeting bacterial DNA gyrase.

PMID- 30282998
TI  - Critical deposition height for sustainable restoration via laser additive
      manufacturing.
AB  - Laser material deposition based restoration of high-value components can be a
      revolutionary technology in remanufacturing. The deposition process induces
      residual stresses due to thermomechanical behavior and metallurgical
      transformations. The presence of tensile residual stresses in the deposited layer
      will compromise the fatigue life of the restored component. We have developed a
      novel fully coupled metallurgical, thermal and mechanical (metallo
      thermomechanical) model to predict residual stresses and identified a critical
      deposition height, which ensures compressive residual stresses in the deposited
      layer. Any lower deposition height will result in tensile residual stresses and
      higher deposition height will result in excessive dilution (substrate melting).
      We have validated the model using neutron and micro-focus X-ray diffraction
      measurements. This study highlights that the critical deposition height
      corresponds to the minimum cooling rate during solidification. It addresses one
      of the major outstanding problems of additive manufacturing and paves a way for
      "science-enabled-technology" solutions for sustainable
      restoration/remanufacturing.

PMID- 30282999
TI  - Cholesterol is Inefficiently Converted to Cholesteryl Esters in the Blood of
      Cardiovascular Disease Patients.
AB  - Shotgun lipidomic analysis of 203 lipids in 13 lipid classes performed on blood
      plasma of donors who had just suffered an acute coronary syndrome (ACS, n = 74),
      or an ischemic stroke (IS, n = 21), or who suffer from stable angina pectoris
      (SAP, n = 78), and an age-matched control cohort (n = 52), showed some of the
      highest inter-lipid class correlations between cholesteryl esters (CE) and
      phosphatidylcholines (PC) sharing a common fatty acid. The concentration of
      lysophospatidylcholine (LPC) and ratios of concentrations of CE to free
      cholesterol (Chol) were also lower in the CVD cohorts than in the control cohort,
      indicating a deficient conversion of Chol to CE in the blood plasma in the CVD
      subjects. A non-equilibrium reaction quotient, Q', describing the global
      homeostasis of cholesterol as manifested in the blood plasma was shown to have a
      value in the CVD cohorts (Q'ACS = 0.217 +/- 0.084; Q'IS = 0.201 +/- 0.084; Q'SAP
      = 0.220 +/- 0.071) that was about one third less than in the control cohort
      (Q'Control = 0.320 +/- 0.095, p < 1 * 10-4), suggesting its potential use as a
      rapid predictive/diagnostic measure of CVD-related irregularities in cholesterol
      homeostasis.

PMID- 30283000
TI  - Protein-protein interactions reveal key canonical pathways, upstream regulators,
      interactome domains, and novel targets in ALS.
AB  - Developing effective treatment strategies for neurodegenerative diseases require
      an understanding of the underlying cellular pathways that lead to neuronal
      vulnerability and progressive degeneration. To date, numerous mutations in 147
      distinct genes are identified to be "associated" with, "modifier" or "causative"
      of amyotrophic lateral sclerosis (ALS). Protein products of these genes and their
      interactions helped determine the protein landscape of ALS, and revealed upstream
      modulators, key canonical pathways, interactome domains and novel therapeutic
      targets. Our analysis originates from known human mutations and circles back to
      human, revealing increased PPARG and PPARGC1A expression in the Betz cells of
      sALS patients and patients with TDP43 pathology, and emphasizes the importance of
      lipid homeostasis. Downregulation of YWHAZ, a 14-3-3 protein, and cytoplasmic
      accumulation of ZFYVE27 especially in diseased Betz cells of ALS patients
      reinforce the idea that perturbed protein communications, interactome defects,
      and altered converging pathways will reveal novel therapeutic targets in ALS.

PMID- 30283002
TI  - Can neuroimaging help combat the opioid epidemic? A systematic review of clinical
      and pharmacological challenge fMRI studies with recommendations for future
      research.
AB  - The current opioid epidemic is an urgent public health problem, with enormous
      individual, societal, and healthcare costs. Despite effective, evidence-based
      treatments, there is significant individual variability in treatment responses
      and relapse rates are high. In addition, the neurobiology of opioid-use disorder
      (OUD) and its treatment is not well understood. This review synthesizes published
      fMRI literature relevant to OUD, with an emphasis on findings related to opioid
      medications and treatment, and proposes areas for further research. We conducted
      a systematic literature review of Medline and Psychinfo to identify (i) fMRI
      studies comparing OUD and control participants; (ii) studies related to
      medication, treatment, abstinence or withdrawal effects in OUD; and (iii) studies
      involving manipulation of the opioid system in healthy individuals. Following
      application of exclusionary criteria (e.g., insufficient sample size), 45 studies
      were retained comprising data from ~1400 individuals. We found convergent
      evidence that individuals with OUD display widespread heightened neural
      activation to heroin cues. This pattern is potentiated by heroin, attenuated by
      medication-assisted treatments for opioids, predicts treatment response, and is
      reduced following extended abstinence. Nonetheless, there is a paucity of
      literature examining neural characteristics of OUD and its treatment. We discuss
      limitations of extant research and identify critical areas for future
      neuroimaging studies, including the urgent need for studies examining
      prescription opioid users, assessing sex differences and utilizing a wider range
      of clinically relevant task-based fMRI paradigms across different stages of
      addiction.

PMID- 30283001
TI  - Deletion of the type 2 metabotropic glutamate receptor increases heroin abuse
      vulnerability in transgenic rats.
AB  - Opioid abuse is a rapidly growing public health crisis in the USA. Despite
      extensive research in the past decades, little is known about the etiology of
      opioid addiction or the neurobiological risk factors that increase vulnerability
      to opioid use and abuse. Recent studies suggest that the type 2 metabotropic
      glutamate receptor (mGluR2) is critically involved in substance abuse and
      addiction. In the present study, we evaluated whether low-mGluR2 expression may
      represent a risk factor for the development of opioid abuse and addiction using
      transgenic mGluR2-knockout (mGluR2-KO) rats. Compared to wild-type controls,
      mGluR2-KO rats exhibited higher nucleus accumbens (NAc) dopamine (DA) and
      locomotor responses to heroin, higher heroin self-administration and heroin
      intake, more potent morphine-induced analgesia and more severe naloxone
      precipitated withdrawal symptoms. In contrast, mGluR2-KO rats displayed lower
      motivation for heroin self-administration under high price progressive-ratio (PR)
      reinforcement conditions. Taken together, these findings suggest that mGluR2 may
      play an inhibitory role in opioid action, such that deletion of this receptor
      results in an increase in brain DA responses to heroin and in acute opioid reward
      and analgesia. Low-mGluR2 expression in the brain may therefore be a risk factor
      for the initial development of opioid abuse and addiction.

PMID- 30283003
TI  - Ancient proteins from ceramic vessels at Catalhoyuk West reveal the hidden
      cuisine of early farmers.
AB  - The analysis of lipids (fats, oils and waxes) absorbed within archaeological
      pottery has revolutionized the study of past diets and culinary practices.
      However, this technique can lack taxonomic and tissue specificity and is often
      unable to disentangle signatures resulting from the mixing of different food
      products. Here, we extract ancient proteins from ceramic vessels from the West
      Mound of the key early farming site of Catalhoyuk in Anatolia, revealing that
      this community processed mixes of cereals, pulses, dairy and meat products, and
      that particular vessels may have been reserved for specialized foods (e.g., cow
      milk and milk whey). Moreover, we demonstrate that dietary proteins can persist
      on archaeological artefacts for at least 8000 years, and that this approach can
      reveal past culinary practices with more taxonomic and tissue-specific clarity
      than has been possible with previous biomolecular techniques.

PMID- 30283004
TI  - Absence of Parallel Fibre to Purkinje Cell LTD During Eyeblink Conditioning.
AB  - Long-term depression (LTD) of parallel fibre/Purkinje cell synapses has been the
      favoured explanation for cerebellar motor learning such as classical eyeblink
      conditioning. Previous evidence against this interpretation has been contested.
      Here we wanted to test whether a classical conditioning protocol causes LTD. We
      applied a conditioning protocol, using a train of electrical pulses to the
      parallel fibres as the conditional stimulus. In order to rule out indirect
      effects caused by antidromic granule cell activation or output from Purkinje
      cells that might produce changes in Purkinje cell responsiveness, we focused the
      analysis on the first pulse in the conditional stimulus, that is, before any
      indirect effects would have time to occur. Purkinje cells learned to respond with
      a firing pause to the conditional stimulus. Yet, there was no depression of
      parallel fibre excitation after training.

PMID- 30283005
TI  - Profiling inflammatory markers in patients with pneumonia on intensive care.
AB  - Clinical investigations lack predictive value when diagnosing pneumonia,
      especially when patients are ventilated and develop ventilator associated
      pneumonia (VAP). New tools to aid diagnosis are important to improve outcomes.
      This pilot study examines the potential for a panel of inflammatory mediators to
      aid in the diagnosis. Forty-four ventilated patients, 17 with pneumonia and 27
      with brain injuries, eight of whom developed VAP, were recruited. 51 inflammatory
      mediators, including cytokines and oxylipins, were measured in patients' serum
      using flow cytometry and mass spectrometry. The mediators could separate patients
      admitted to ICU with pneumonia compared to brain injury with an area under the
      receiver operating characteristic curve (AUROC) 0.75 (0.61-0.90). Changes in
      inflammatory mediators were similar in both groups over the course of ICU stay
      with 5,6-dihydroxyeicosatrienoic and 8,9-dihydroxyeicosatrienoic acids increasing
      over time and interleukin-6 decreasing. However, brain injured patients who
      developed VAP maintained inflammatory profiles similar to those at admission. A
      multivariate model containing 5,6-dihydroxyeicosatrienoic acid, 8,9
      dihydroxyeicosatrienoic acid, intercellular adhesion molecule-1, interleukin-6,
      and interleukin-8, could differentiate patients with VAP from brain injured
      patients without infection (AUROC 0.94 (0.80-1.00)). The use of a selected group
      of markers showed promise to aid the diagnosis of VAP especially when combined
      with clinical data.

PMID- 30283006
TI  - Superconductivity at 38 K at an electrochemical interface between an ionic liquid
      and FeSe0.8Te0.2 on various substrates.
AB  - Superconducting FeSe0.8Te0.2 thin films on SrTiO3, LaAlO3 and CaF2 substrates
      were electrochemically etched in an ionic liquid, DEME-TFSI, electrolyte with a
      gate bias of 5 V. Superconductivity at 38 K was observed on all substrates after
      the etching of films with a thickness greater than 30 nm, despite the different
      Tc values of 8 K, 12 K and 19 K observed before etching on SrTiO3, LaAlO3 and
      CaF2 substrates, respectively. Tc returned to its original value with the removal
      of the gate bias. The observation of Tc enhancement for these thick films
      indicates that the Tc enhancement is unrelated to any interfacial effects between
      the film and the substrate. The sheet resistance and Hall coefficient of the
      surface conducting layer were estimated from the gate bias dependence of the
      transport properties. The sheet resistances of the surface conducting layers of
      the films on LaAlO3 and CaF2 showed identical temperature dependence, and the
      Hall coefficient was found to be almost independent of temperature and to take
      values of -0.05 to -0.2 m2/C, corresponding to 4-17 electrons per FeSe0.8Te0.2
      unit cell area in two dimensions. These common transport properties on various
      substrates suggest that the superconductivity at 38 K appears in the surface
      conducting layer as a result of an electrochemical reaction between the surface
      of the FeSe0.8Te0.2 thin film and the ionic liquid electrolyte.

PMID- 30283007
TI  - Observation of the linewidth broadening of single spins in diamond nanoparticles
      in aqueous fluid and its relation to the rotational Brownian motion.
AB  - Capturing the fast rotational motion of single nanoparticles has been hindered
      owing to the difficulty of acquiring directional information under the optical
      diffraction limit. Here, we report the linewidth broadening of the electron spin
      resonance of single nitrogen vacancy (NV) centers that matches the rotational
      diffusion constant of the host nanodiamonds. When nanodiamonds are gradually
      detached from the substrates that they were fixed to, their optically detected
      spin resonance peaks are broadened by 1.8 MHz, which corresponds to the
      rotational diffusion constant of nanoparticles with a diameter of 11.4 nm from
      the Einstein-Smoluchowski relation.

PMID- 30283009
TI  - moxMaple3: a Photoswitchable Fluorescent Protein for PALM and Protein
      Highlighting in Oxidizing Cellular Environments.
AB  - The ability of fluorescent proteins (FPs) to fold robustly is fundamental to the
      autocatalytic formation of the chromophore. While the importance of the tertiary
      protein structure is well appreciated, the impact of individual amino acid
      mutations for FPs is often not intuitive and requires direct testing. In this
      study, we describe the engineering of a monomeric photoswitchable FP, moxMaple3,
      for use in oxidizing cellular environments, especially the eukaryotic secretory
      pathway. Surprisingly, a point mutation to replace a cysteine substantially
      improved the yield of correctly folded FP capable of chromophore formation,
      regardless of cellular environment. The improved folding of moxMaple3 increases
      the fraction of visibly tagged fusion proteins, as well as FP performance in PALM
      super-resolution microscopy, and thus makes moxMaple3 a robust monomeric FP
      choice for PALM and optical highlighting applications.

PMID- 30283008
TI  - Cytoplasmic localization of GRHL3 upon epidermal differentiation triggers cell
      shape change for epithelial morphogenesis.
AB  - Epithelial cell shape change is a pivotal driving force for morphogenesis of
      complex three-dimensional architecture. However, molecular mechanisms triggering
      shape changes of epithelial cells in the course of growth and differentiation
      have not been entirely elucidated. Grhl3 plays a crucial role as a downstream
      transcription factor of Wnt/beta-catenin in epidermal differentiation. Here, we
      show Grhl3 induced large, mature epidermal cells, enriched with actomyosin
      networks, from embryoid bodies in vitro. Such epidermal cells were apparently
      formed by the simultaneous activation of canonical and non-canonical Wnt
      signaling pathways. A nuclear transcription factor, GRHL3 is localized in the
      cytoplasm and cell membrane during epidermal differentiation. Subsequently, such
      extranuclear GRHL3 is essential for the membrane-associated expression of VANGL2
      and CELSR1. Cytoplasmic GRHL3, thereby, allows epidermal cells to acquire
      mechanical properties for changes in epithelial cell shape. Thus, we propose that
      cytoplasmic localization of GRHL3 upon epidermal differentiation directly
      triggers epithelial morphogenesis.

PMID- 30283010
TI  - Bufonid herpesvirus 1 (BfHV1) associated dermatitis and mortality in free ranging
      common toads (Bufo bufo) in Switzerland.
AB  - Here we report the discovery and partial characterization of a novel herpesvirus
      tentatively named Bufonid herpesvirus 1 (BfHV1) from severe dermatitis in free
      ranging common toads (Bufo bufo) in Switzerland. The disease has been observed in
      toads every year since 2014, in spring, during the mating season, at different
      and distant locations. The virus is found in the skin and occasionally in the
      brain of infected toads. The genome of the virus is at least 158 Kb long and
      contains at least 152 open reading frames with a minimal length of 270 nt. The
      genome of BfHV1 contains all the signature genes that are present in
      alloherpesviruses. Phylogenetic analysis based on the amino acid sequence of the
      DNA polymerase and terminase proteins positions the novel virus among the members
      of the genus Batrachovirus, family Alloherpesviridae. This is the first
      herpesvirus ever characterized in common toads.

PMID- 30283011
TI  - Fabry-Perot cavity resonance enabling highly polarization-sensitive double-layer
      gold grating.
AB  - We present experimental and theoretical investigations on the polarization
      properties of a single- and a double-layer gold (Au) grating, serving as a wire
      grid polarizer. Two layers of Au gratings form a cavity that effectively
      modulates the transmission and reflection of linearly polarized light.
      Theoretical calculations based on a transfer matrix method reveals that the
      double-layer Au grating structure creates an optical cavity exhibiting Fabry
      Perot (FP) resonance modes. As compared to a single-layer grating, the FP cavity
      resonance modes of the double-layer grating significantly enhance the
      transmission of the transverse magnetic (TM) mode, while suppressing the
      transmission of the transverse electric (TE) mode. As a result, the extinction
      ratio of TM to TE transmission for the double-layer grating structure is improved
      by a factor of approximately 8 in the mid-wave infrared region of 3.4-6 MUm.
      Furthermore, excellent infrared imagery is obtained with over a 600% increase in
      the ratio of the TM-output voltage (Vtheta = 0 degrees ) to TE-output voltage
      (Vtheta = 90 degrees ). This double-layer Au grating structure has great
      potential for use in polarimetric imaging applications due to its superior
      ability to resolve linear polarization signatures.

PMID- 30283012
TI  - Enhanced voltage generation through electrolyte flow on liquid-filled surfaces.
AB  - The generation of electrical voltage through the flow of an electrolyte over a
      charged surface may be used for energy transduction. Here, we show that enhanced
      electrical potential differences (i.e., streaming potential) may be obtained
      through the flow of salt water on liquid-filled surfaces that are infiltrated
      with a lower dielectric constant liquid, such as oil, to harness electrolyte slip
      and associated surface charge. A record-high figure of merit, in terms of the
      voltage generated per unit applied pressure, of 0.043 mV Pa-1 is obtained through
      the use of the liquid-filled surfaces. In comparison with air-filled surfaces,
      the figure of merit associated with the liquid-filled surface increases by a
      factor of 1.4. These results lay the basis for innovative surface charge
      engineering methodology for the study of electrokinetic phenomena at the
      microscale, with possible application in new electrical power sources.

PMID- 30283013
TI  - Feasibility and robustness of dynamic 18F-FET PET based tracer kinetic models
      applied to patients with recurrent high-grade glioma prior to carbon ion
      irradiation.
AB  - The aim of this study was to analyze the robustness and diagnostic value of
      different compartment models for dynamic 18F-FET PET in recurrent high-grade
      glioma (HGG). Dynamic 18F-FET PET data of patients with recurrent WHO grade III
      (n:7) and WHO grade IV (n: 9) tumors undergoing re-irradiation with carbon ions
      were analyzed by voxelwise fitting of the time-activity curves with a simplified
      and an extended one-tissue compartment model (1TCM) and a two-tissue compartment
      model (2TCM), respectively. A simulation study was conducted to assess robustness
      and precision of the 2TCM. Parameter maps showed enhanced detail on tumor
      substructure. Neglecting the blood volume VB in the 1TCM yields insufficient
      results. Parameter K1 from both 1TCM and 2TCM showed correlation with overall
      patient survival after carbon ion irradiation (p = 0.043 and 0.036,
      respectively). The 2TCM yields realistic estimates for tumor blood volume, which
      was found to be significantly higher in WHO IV compared to WHO III (p = 0.031).
      Simulations on the 2TCM showed that K1 yields good accuracy and robustness while
      k2 showed lowest stability of all parameters. The 1TCM provides the best
      compromise between parameter stability and model accuracy; however application of
      the 2TCM is still feasible and provides a more accurate representation of tracer
      kinetics at the cost of reduced robustness. Detailed tracer kinetic analysis of
      18F-FET PET with compartment models holds valuable information on tumor
      substructures and provides additional diagnostic and prognostic value.

PMID- 30283014
TI  - Chronic lymphocytic leukemia treatment algorithm 2018.
AB  - The treatment landscape for patients with chronic lymphocytic leukemia (CLL) has
      changed considerably with the introduction of very effective oral targeted
      therapies (such as ibrutinib, idelalisib, and venetoclax), and next-generation
      anti-CD20 monoclonal antibodies (such as obinutuzumab). These agents lead to
      improved outcomes in CLL, even among patients with high-risk features, such as
      del17p13 or TP53 mutation and unmutated immunoglobulin heavy chain (IGHV) genes.
      Each of these treatments is associated with a unique toxicity profile; in the
      absence of randomized data, the choice of one type of treatment over another
      depends on the co-morbidities of the patient. Chemoimmunotherapy still plays an
      important role in the management of previously untreated CLL patients,
      particularly among young fit patients who have standard risk FISH profile and
      mutated IGHV genes. Richter's transformation of CLL remains a difficult
      complication to treat, although therapy with programmed death 1 inhibitors such
      as pembrolizumab and nivolumab has shown impressive responses in a subset of
      patients. Our ability to risk stratify CLL patients continues to evolve; the CLL
      International Prognostic Index (CLL-IPI) is the best validated tool in predicting
      time to first therapy among previously untreated patients. This review summarizes
      the current approach to risk stratification and management of CLL patients.

PMID- 30283015
TI  - Graphitic Carbon Electrodes on Flexible Substrate for Neural Applications
      Entirely Fabricated Using Infrared Nanosecond Laser Technology.
AB  - Neural interfaces for neuroscientific research are nowadays mainly manufactured
      using standard microsystems engineering technologies which are incompatible with
      the integration of carbon as electrode material. In this work, we investigate a
      new method to fabricate graphitic carbon electrode arrays on flexible substrates.
      The devices were manufactured using infrared nanosecond laser technology for both
      patterning all components and carbonizing the electrode sites. Two laser pulse
      repetition frequencies were used for carbonization with the aim of finding the
      optimum. Prototypes of the devices were evaluated in vitro in 30 mM hydrogen
      peroxide to mimic the post-surgery oxidative environment. The electrodes were
      subjected to 10 million biphasic pulses (39.5 MUC/cm2) to measure their stability
      under electrical stress. Their biosensing capabilities were evaluated in
      different concentrations of dopamine in phosphate buffered saline solution. Raman
      spectroscopy and x-ray photoelectron spectroscopy analysis show that the atomic
      percentage of graphitic carbon in the manufactured electrodes reaches the
      remarkable value of 75%. Results prove that the infrared nanosecond laser yields
      activated graphite electrodes that are conductive, non-cytotoxic and
      electrochemically inert. Their comprehensive assessment indicates that our laser
      induced carbon electrodes are suitable for future transfer into in vivo studies,
      including neural recordings, stimulation and neurotransmitters detection.

PMID- 30283016
TI  - Mitochondrial DNA synthesis fuels NLRP3 inflammasome.

PMID- 30283017
TI  - The interactions between botulinum-toxin-based facial treatments and embodied
      emotions.
AB  - Botulinum toxin (BTX) injections reduce muscle mobility and are commonly used to
      treat the appearance of glabellar frown lines. Research shows that this cosmetic
      treatment leads to a reduction in depression. This reduction is consistent with
      the theory of embodied emotions because patients have a reduced ability to frown
      and so receive less negative feedback associated with this action. The current
      research explored this effect and three further hypotheses for the effects of
      cosmetic BTX injections based on embodied emotions. It was hypothesised that
      treatment of crow's feet (or laughter lines) would reduce mood as patients'
      Duchenne smiles would be impaired. It was hypothesised that facial BTX treatments
      would impair emotional expression recognition because the ability to mimic
      emotions would be reduced. Finally, it was hypothesised that, as BTX treatments
      prevent facial expressions associated with sexual excitement, sexual function
      would be impaired after treatment. Twenty four BTX-treated and twelve matched
      participants (all female) were tested before and after treatment. Results found
      that BTX treatment of laughter lines was associated with increased depression
      scores. Further, BTX treatment was associated with reduced emotion recognition
      ability and sexual function. The current results add to our knowledge of the
      psychological effects of injections of powerful neurotoxins and broaden the scope
      of the embodiment of emotions.

PMID- 30283018
TI  - Glycerophosphatidylcholine PC(36:1) absence and 3'-phosphoadenylate (pAp)
      accumulation are hallmarks of the human glioma metabolome.
AB  - Glioma is the most prevalent malignant brain tumor. A comprehensive analysis of
      the glioma metabolome is still lacking. This study aims to explore new special
      metabolites in glioma tissues. A non-targeted human glioma metabolomics was
      performed by UPLC-Q-TOF/MS. The gene expressions of 18 enzymes associated with 3'
      phosphoadenylate (pAp) metabolism was examined by qRT-PCR. Those enzymes cover
      the primary metabolic pathway of pAp. We identified 15 new metabolites (13 lipids
      and 2 nucleotides) that were significantly different between the glioma and
      control tissues. Glycerophosphatidylcholine [PC(36:1)] content was high and pAp
      content was significantly low in the control brain (p  < 0.01). In glioma
      tissues, PC(36:1) was not detected and pAp content was significantly increased.
      The gene expressions of 3'-nucleotidases (Inositol monophosphatase (IMPAD-1) and
      3'(2'),5'-bisphosphate nucleotidase 1(BPNT-1)) were dramatically down-regulated.
      Meanwhile, the gene expression of 8 sulfotransferases (SULT), 2 phosphoadenosine
      phosphosulfate synthases (PAPSS-1 and PAPSS-2) and L-aminoadipate-semialdehyde
      dehydrogenase-phosphopante-theinyl transferase (AASDHPPT) were up-regulated.
      PC(36:1) absence and pAp accumulation are the most noticeable metabolic
      aberration in glioma. The dramatic down-regulation of IMPAD-1 and BPNT-1 are the
      primary cause for pAp dramatic accumulation. Our findings suggest that
      differential metabolites discovered in glioma could be used as potentially novel
      therapeutic targets or diagnostic biomarkers and that abnormal metabolism of
      lipids and nucleotides play roles in the pathogenesis of glioma.

PMID- 30283019
TI  - Reprogramming of regulatory network using expression uncovers sex-specific gene
      regulation in Drosophila.
AB  - Gene regulatory networks (GRNs) describe regulatory relationships between
      transcription factors (TFs) and their target genes. Computational methods to
      infer GRNs typically combine evidence across different conditions to infer
      context-agnostic networks. We develop a method, Network Reprogramming using
      EXpression (NetREX), that constructs a context-specific GRN given context
      specific expression data and a context-agnostic prior network. NetREX remodels
      the prior network to obtain the topology that provides the best explanation for
      expression data. Because NetREX utilizes prior network topology, we also develop
      PriorBoost, a method that evaluates a prior network in terms of its consistency
      with the expression data. We validate NetREX and PriorBoost using the "gold
      standard" E. coli GRN from the DREAM5 network inference challenge and apply them
      to construct sex-specific Drosophila GRNs. NetREX constructed sex-specific
      Drosophila GRNs that, on all applied measures, outperform networks obtained from
      other methods indicating that NetREX is an important milestone toward building
      more accurate GRNs.

PMID- 30283020
TI  - Creating a switchable optical cavity with controllable quantum-state mapping
      between two modes.
AB  - We describe how an ensemble of four-level atoms in the diamond-type configuration
      can be applied to create a fully controllable effective coupling between two
      cavity modes. The diamond-type configuration allows one to use a bimodal cavity
      that supports modes of different frequencies or different circular polarisations,
      because each mode is coupled only to its own transition. This system can be used
      for mapping a quantum state of one cavity mode onto the other mode on demand.
      Additionally, it can serve as a fast opening high-Q cavity system that can be
      easily and coherently controlled with laser fields.

PMID- 30283022
TI  - The interplay of exercise, placebo and nocebo effects on experimental pain.
AB  - Over the last few decades, placebo, and nocebo effects in general, have been
      investigated at rest. This proposed study explores whether they could work even
      when the experience of pain occurs during a movement. Exercise itself can have a
      hypoalgesic effect, suggesting that placebo- and exercise-induced hypoalgesia
      could foster pain reduction. In the present study, we investigated the interplay
      of exercise, placebo and nocebo effects on pain. To this aim, we developed a
      machine-controlled isotonic motor task to standardize the exercise across
      participants and used a well-validated model of placebo and nocebo manipulations
      with reinforced expectations via a conditioning procedure including visual cues
      paired with heat painful stimulations. Participants reported expectations and
      pain on a trial-by-trial basis. We found that the standardized isotonic exercise
      elicited a reduction of pain intensity. Moreover, both exercise and placebo
      induced comparable hypoalgesic effects. When the exercise was added, placebo and
      nocebo effects were influenced by expectations but were not affected by fatigue
      or sex differences. Exercise-, placebo- and nocebo-induced pain modulation are
      likely to work through distinct mechanisms and neurophysiological research is
      needed to fully exploit the implications for sport, rehabilitation and pain
      management.

PMID- 30283021
TI  - The relationship between transgenerational acquired resistance and global DNA
      methylation in Arabidopsis.
AB  - Progeny of heavily diseased plants develop transgenerational acquired resistance
      (TAR). In Arabidopsis, TAR can be transmitted over one stress-free generation.
      Although DNA methylation has been implicated in the regulation of TAR, the
      relationship between TAR and global DNA methylation remains unknown. Here, we
      characterised the methylome of TAR-expressing Arabidopsis at different
      generations after disease exposure. Global clustering of cytosine methylation
      revealed TAR-related patterns in the F3 generation, but not in the F1 generation.
      The majority of differentially methylated positions (DMPs) occurred at CG context
      in gene bodies. TAR in F3 progeny after one initial generation of disease,
      followed by two stress-free generations, was lower than TAR in F3 progeny after
      three successive generations of disease. This difference in TAR effectiveness was
      proportional to the intensity of differential methylation at a sub-set of
      cytosine positions. Comparison of TAR-related DMPs with previously characterised
      cytosine methylation in mutation accumulation lines revealed that ancestral
      disease stress preferentially acts on methylation-labile cytosine positions, but
      also extends to methylation-stable positions. Thus, the TAR-related impact of
      ancestral disease extends beyond stochastic variation in DNA methylation. Our
      study has shown that the Arabidopsis epigenome responds globally to disease in
      previous generations and we discuss its contribution to TAR.

PMID- 30283024
TI  - Conduction Mechanisms on High Retention Annealed MgO-based Resistive Switching
      Memory Devices.
AB  - We report on the conduction mechanisms of novel Ru/MgO/Cu and Ru/MgO/Ta resistive
      switching memory (RSM) devices. Current-voltage (I-V) measurements revealed
      Schottky emission (SE) as the dominant conduction mechanism in the high
      resistance state (HRS), which was validated by varying temperatures and
      transmission electron microscopy (TEM) results. Retention of more than 10 years
      at 85  degrees C was obtained for both Ru/MgO/Ta and Ru/MgO/Cu RSM devices. In
      addition, annealing processes greatly improved the consistency of HRS and LRS
      switching paths from cycle to cycle, exhibiting an average ON/OFF ratio of 102.
      Further TEM studies also highlighted the difference in crystallinity between
      different materials in Ru/MgO/Cu RSM devices, confirming Cu filament
      identification which was found to be 10 nm in width.

PMID- 30283023
TI  - Reappraising the microscopic anatomy of human testis: identification of telocyte
      networks in the peritubular and intertubular stromal space.
AB  - Telocytes are a recently described stromal cell type widely distributed in
      various organs including the female and male reproductive systems. This study was
      aimed to investigate for the first time the existence, distribution and
      characteristics of telocytes in normal human testis by an integrated
      morphological approach (immunohistochemistry, immunofluorescence and transmission
      electron microscopy). We found that telocytes displaying typical long and
      moniliform prolongations and coexpressing CD34 and PDGFRalpha formed networks in
      the outer layer of peritubular tissue and around Leydig cells and vessels in the
      intertubular stroma. Testicular telocytes were immunophenotypically negative for
      CD31, c-kit/CD117 as well as alpha-SMA, thus making them clearly distinguishable
      from myoid cells/myofibroblasts located in the inner layer of peritubular tissue.
      Transmission electron microscopy confirmed the presence of cells
      ultrastructurally identifiable as telocytes (i.e. cells with telopodes
      alternating podomers and podoms) in the aforementioned locations. Intercellular
      contacts between neighboring telocytes and telopodes were observed throughout the
      testicular stromal compartment. Telopodes intimately surrounded and often
      established close contacts with peritubular myoid cells/myofibroblasts, Leydig
      cells and vessels. Extracellular vesicles were also frequently detected near
      telopodes. In summary, we demonstrated that telocytes are a previously neglected
      stromal component of human testis with potential implications in tissue
      homeostasis deserving further investigation.

PMID- 30283025
TI  - Activity of a novel antimicrobial peptide against Pseudomonas aeruginosa
      biofilms.
AB  - With the increasing recognition of biofilms in human disease, the development of
      novel antimicrobial therapies is of critical importance. For example, in patients
      with cystic fibrosis (CF), the acquisition of host-adapted, chronic Pseudomonas
      aeruginosa infection is associated with a decline in lung function and increased
      mortality. Our objective was to test the in vitro efficacy of a membrane-active
      antimicrobial peptide we designed, termed 6K-F17 (sequence: KKKKKK-AAFAAWAAFAA
      NH2), against multidrug resistant P. aeruginosa biofilms. This peptide displays
      high antimicrobial activity against a range of pathogenic bacteria, yet is non
      hemolytic to human erythrocytes and non-toxic to human bronchial epithelial
      cells. In the present work, P. aeruginosa strain PAO1, and four multidrug
      resistant (MDR) isolates from chronically infected CF individuals, were grown as
      48-hour biofilms in a static biofilm slide chamber model. These biofilms were
      then exposed to varying concentrations of 6K-F17 alone, or in the presence of
      tobramycin, prior to confocal imaging. Biofilm biovolume and viability were
      assessed. 6K-F17 was able to kill biofilms - even in the presence of sputum - and
      greatly reduce biofilm biovolume in PAO1 and MDR isolates. Strikingly, when used
      in conjunction with tobramycin, low doses of 6K-F17 significantly potentiated
      tobramycin killing, leading to biofilm destruction.

PMID- 30283026
TI  - Benefits of soil biochar amendments to tomato growth under saline water
      irrigation.
AB  - Biochar amendments have been used in agriculture to improve soil fertility and
      enhance crop productivity. A greenhouse experiment was conducted to test the
      hypothesis that biochar amendment could also enhance the productivity of salt
      affected soils. The trial was conducted over two consecutive growing seasons to
      investigate the effect of biochar amendment (four application rates as: B1 = 0%,
      B2 = 2%, B3 = 4%, and B4 = 8% by mass of soil) on yield and quality of tomatoes
      grown in a silt loam soil using non-saline water (I0 = 0.7 dS m-1) and saline
      water (I1 = 1 dS m-1; I2 = 3 dS m-1) irrigation. Furthermore, the study
      investigated the mechanism by which biochar addresses the salt stress on plant.
      The results showed that soil productivity as indicated by the vegetative growth
      and tomato yield components was adversely and significantly affected by saline
      water irrigation (P < 0.05). Tomato yield decreased from 689 +/- 35.6 to 533 +/-
      79.0 g per plant as salinity of irrigation water increased from I0 to I2. Then,
      biochar amendment increased vegetative growth, yield, and quality parameters
      under saline irrigation water regimes, and ameliorated the salt stresses on crop
      growth. The highest (8.73 +/- 0.15 and 4.10 +/- 0.82 g kg-1) and the lowest (8.33
      +/- 0.08 and 2.42 +/- 0.76 g kg-1) values of soil pH and soil organic matter were
      measured at B4I0 and B1I2 treatments, respectively. Also, the highest rate of
      biochar amendment combining with non-saline water irrigation (B4I0) produced
      tomato with the highest plant photosynthetic (17.08 +/- 0.19 MUmol m-2 s-1) and
      transpiration rate (8.16 +/- 0.18 mmol H2O m-2 s-1). Mechanically, biochar
      amendment reduced transient sodium ions by adsorption and released mineral
      nutrients such as potassium, calcium, and magnesium into the soil solution.
      Therefore, biochar amendments have the potential in ameliorating salt stress and
      enhancing tomato production.

PMID- 30283028
TI  - Ethical concerns regarding Danish genetic research.

PMID- 30283029
TI  - Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as
      adjunctive therapy in treatment-resistant depression (TRD).
AB  - : Numerous placebo-controlled studies have demonstrated the ability of ketamine,
      an NMDA receptor antagonist, to induce rapid (within hours), transient
      antidepressant effects when administered intravenously (IV) at subanesthetic
      doses (0.5 mg/kg over 40 min). However, the optimal antidepressant dose remains
      unknown. We aimed to compare to active placebo the rapid acting antidepressant
      properties of a broad range of subanesthetic doses of IV ketamine among
      outpatients with treatment-resistant depression (TRD). A range of IV ketamine
      doses were compared to active placebo in the treatment of adult TRD over a 3-day
      period following a single infusion over 40 min. This was an outpatient study
      conducted across six US academic sites. Outpatients were 18-70 years old with
      TRD, defined as failure to achieve a satisfactory response (e.g., less than 50%
      improvement of depression symptoms) to at least two adequate treatment courses
      during the current depressive episode. Following a washout period, 99 eligible
      subjects were randomly assigned to one of the five arms in a 1:1:1:1:1 fashion: a
      single intravenous dose of ketamine 0.1 mg/kg (n = 18), a single dose of ketamine
      0.2 mg/kg (n = 20), a single dose of ketamine 0.5 mg/kg (n = 22), a single dose
      of ketamine 1.0 mg/kg (n = 20), and a single dose of midazolam 0.045 mg/kg
      (active placebo) (n = 19). The study assessments (HAM-D-6, MADRS, SDQ, PAS, CGI
      S, and CGI-I) were performed at days 0, 1, 3 (endpoint), 5, 7, 14, and 30 to
      assess the safety and efficacy. The overall group * time interaction effect was
      significant for the primary outcome measure, the HAM-D-6. In post hoc pairwise
      comparisons controlling for multiple comparisons, standard dose (0.5 mg/kg) and
      high dose (1 mg/kg) of intravenous ketamine were superior to active placebo; a
      low dose (0.1 mg/kg) was significant only prior to adjustment (p = 0.02, p-adj =
      0.14, d = -0.82 at day 1). Most of the interaction effect was due to differences
      at day 1, with no significant adjusted pairwise differences at day 3. This
      pattern generally held for secondary outcomes. The infusions of ketamine were
      relatively well tolerated compared to active placebo, except for greater
      dissociative symptoms and transient blood pressure elevations with the higher
      doses. Our results suggest that there is evidence for the efficacy of the 0.5
      mg/kg and 1.0 mg/kg subanesthetic doses of IV ketamine and no clear or consistent
      evidence for clinically meaningful efficacy of lower doses of IV ketamine. TRIAL
      REGISTRATION: NCT01920555.

PMID- 30283030
TI  - Baseline brain structural and functional predictors of clinical outcome in the
      early course of schizophrenia.
AB  - Although schizophrenia is considered a brain disorder, the role of brain
      organization for symptomatic improvement remains inadequately defined. We
      investigated the relationship between baseline brain morphology, resting-state
      network connectivity and clinical response after 24-weeks of antipsychotic
      treatment in patients with schizophrenia (n = 95) using integrated multivariate
      analyses. There was no significant association between clinical response and
      measures of cortical thickness (r = 0.37, p = 0.98) and subcortical volume (r =
      0.56, p = 0.15). By contrast, we identified a strong mode of covariation linking
      functional network connectivity to clinical response (r = 0.70; p = 0.04), and
      particularly to improvement in positive (weight = 0.62) and anxious/depressive
      symptoms (weight = 0.49). Higher internal cohesiveness of the default mode
      network was the single most important positive predictor. Key negative predictors
      involved the functional cohesiveness of central executive subnetworks anchored in
      the frontoparietal cortices and subcortical regions (including the thalamus and
      striatum) and the inter-network integration between the default mode and
      sensorimotor networks. The present findings establish links between clinical
      response and the functional organization of brain networks involved both in
      perception and in spontaneous and goal-directed cognition, thereby advancing our
      understanding of the pathophysiology of schizophrenia.

PMID- 30283027
TI  - The intellectual disability gene PQBP1 rescues Alzheimer's disease pathology.
AB  - Early-phase pathologies of Alzheimer's disease (AD) are attracting much attention
      after clinical trials of drugs designed to remove beta-amyloid (Abeta) aggregates
      failed to recover memory and cognitive function in symptomatic AD patients. Here,
      we show that phosphorylation of serine/arginine repetitive matrix 2 (SRRM2) at
      Ser1068, which is observed in the brains of early phase AD mouse models and
      postmortem end-stage AD patients, prevents its nuclear translocation by
      inhibiting interaction with T-complex protein subunit alpha. SRRM2 deficiency in
      neurons destabilized polyglutamine binding protein 1 (PQBP1), a causative gene
      for intellectual disability (ID), greatly affecting the splicing patterns of
      synapse-related genes, as demonstrated in a newly generated PQBP1-conditional
      knockout model. PQBP1 and SRRM2 were downregulated in cortical neurons of human
      AD patients and mouse AD models, and the AAV-PQBP1 vector recovered RNA splicing,
      the synapse phenotype, and the cognitive decline in the two mouse models.
      Finally, the kinases responsible for the phosphorylation of SRRM2 at Ser1068 were
      identified as ERK1/2 (MAPK3/1). These results collectively reveal a new aspect of
      AD pathology in which a phosphorylation signal affecting RNA splicing and synapse
      integrity precedes the formation of extracellular Abeta aggregates and may
      progress in parallel with tau phosphorylation.

PMID- 30283031
TI  - Integrative approach to sporadic Alzheimer's disease: deficiency of TYROBP in a
      tauopathy mouse model reduces C1q and normalizes clinical phenotype while
      increasing spread and state of phosphorylation of tau.
AB  - TYROBP/DAP12 forms complexes with ectodomains of immune receptors (TREM2,
      SIRPbeta1, CR3) associated with Alzheimer's disease (AD) and is a network hub and
      driver in the complement subnetwork identified by multi-scale gene network
      studies of postmortem human AD brain. Using transgenic or viral approaches, we
      characterized in mice the effects of TYROBP deficiency on the phenotypic and
      pathological evolution of tauopathy. Biomarkers usually associated with worsening
      clinical phenotype (i.e., hyperphosphorylation and increased tauopathy spreading)
      were unexpectedly increased in MAPTP301S;Tyrobp-/- mice despite the improved
      learning behavior and synaptic function relative to controls with normal levels
      of TYROBP. Notably, levels of complement cascade initiator C1q were reduced in
      MAPTP301S;Tyrobp-/- mice, consistent with the prediction that C1q reduction
      exerts a neuroprotective effect. These observations suggest a model wherein
      TYROBP-KO-(knock-out)-associated reduction in C1q is associated with normalized
      learning behavior and electrophysiological properties in tauopathy model mice
      despite a paradoxical evolution of biomarker signatures usually associated with
      neurological decline.

PMID- 30283032
TI  - Integrative approach to sporadic Alzheimer's disease: deficiency of TYROBP in
      cerebral Abeta amyloidosis mouse normalizes clinical phenotype and complement
      subnetwork molecular pathology without reducing Abeta burden.
AB  - Integrative gene network approaches enable new avenues of exploration that
      implicate causal genes in sporadic late-onset Alzheimer's disease (LOAD)
      pathogenesis, thereby offering novel insights for drug-discovery programs. We
      previously constructed a probabilistic causal network model of sporadic LOAD and
      identified TYROBP/DAP12, encoding a microglial transmembrane signaling
      polypeptide and direct adapter of TREM2, as the most robust key driver gene in
      the network. Here, we show that absence of TYROBP/DAP12 in a mouse model of AD
      type cerebral Abeta amyloidosis (APPKM670/671NL/PSEN1Deltaexon9) recapitulates
      the expected network characteristics by normalizing the transcriptome of
      APP/PSEN1 mice and repressing the induction of genes involved in the switch from
      homeostatic microglia to disease-associated microglia (DAM), including Trem2,
      complement (C1qa, C1qb, C1qc, and Itgax), Clec7a and Cst7. Importantly, we show
      that constitutive absence of TYROBP/DAP12 in the amyloidosis mouse model
      prevented appearance of the electrophysiological and learning behavior
      alterations associated with the phenotype of APPKM670/671NL/PSEN1Deltaexon9 mice.
      Our results suggest that TYROBP/DAP12 could represent a novel therapeutic target
      to slow, arrest, or prevent the development of sporadic LOAD. These data
      establish that the network pathology observed in postmortem human LOAD brain can
      be faithfully recapitulated in the brain of a genetically manipulated mouse.
      These data also validate our multiscale gene networks by demonstrating how the
      networks intersect with the standard neuropathological features of LOAD.

PMID- 30283033
TI  - Cocaine-induced ischemia in prefrontal cortex is associated with escalation of
      cocaine intake in rodents.
AB  - Cocaine-induced vasoconstriction reduces blood flow, which can jeopardize
      neuronal function and in the prefrontal cortex (PFC) it may contribute to
      compulsive cocaine intake. Here, we used integrated optical imaging in a rat self
      administration and a mouse noncontingent model, to investigate whether changes in
      the cerebrovascular system in the PFC contribute to cocaine self-administration,
      and whether they recover with detoxification. In both animal models, cocaine
      induced severe vasoconstriction and marked reductions in cerebral blood flow
      (CBF) in the PFC, which were exacerbated with chronic exposure and with
      escalation of cocaine intake. Though there was a significant proliferation of
      blood vessels in areas of vasoconstriction (angiogenesis), CBF remained reduced
      even after 1 month of detoxification. Treatment with Nifedipine (Ca2+ antagonist
      and vasodilator) prevented cocaine-induced CBF decreases and neuronal Ca2+
      changes in the PFC, and decreased cocaine intake and blocked reinstatement of
      drug seeking. These findings provide support for the hypothesis that cocaine
      induced CBF reductions lead to neuronal deficits that contribute to
      hypofrontality and to compulsive-like cocaine intake in addiction, and document
      that these deficits persist at least one month after detoxification. Our
      preliminary data showed that nifedipine might be beneficial in preventing cocaine
      induced vascular toxicity and in reducing cocaine intake and preventing relapse.

PMID- 30283034
TI  - Uncovering the complex genetics of human character.
AB  - Human personality is 30-60% heritable according to twin and adoption studies.
      Hundreds of genetic variants are expected to influence its complex development,
      but few have been identified. We used a machine learning method for genome-wide
      association studies (GWAS) to uncover complex genotypic-phenotypic networks and
      environmental interactions. The Temperament and Character Inventory (TCI)
      measured the self-regulatory components of personality critical for health (i.e.,
      the character traits of self-directedness, cooperativeness, and self
      transcendence). In a discovery sample of 2149 healthy Finns, we identified sets
      of single-nucleotide polymorphisms (SNPs) that cluster within particular
      individuals (i.e., SNP sets) regardless of phenotype. Second, we identified five
      clusters of people with distinct profiles of character traits regardless of
      genotype. Third, we found 42 SNP sets that identified 727 gene loci and were
      significantly associated with one or more of the character profiles. Each
      character profile was related to different SNP sets with distinct molecular
      processes and neuronal functions. Environmental influences measured in childhood
      and adulthood had small but significant effects. We confirmed the replicability
      of 95% of the 42 SNP sets in healthy Korean and German samples, as well as their
      associations with character. The identified SNPs explained nearly all the
      heritability expected for character in each sample (50 to 58%). We conclude that
      self-regulatory personality traits are strongly influenced by organized
      interactions among more than 700 genes despite variable cultures and
      environments. These gene sets modulate specific molecular processes in brain for
      intentional goal-setting, self-reflection, empathy, and episodic learning and
      memory.

PMID- 30283035
TI  - Dose response of the 16p11.2 distal copy number variant on intracranial volume
      and basal ganglia.
AB  - Carriers of large recurrent copy number variants (CNVs) have a higher risk of
      developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes
      carriers to e.g., autism spectrum disorder and schizophrenia. We compared
      subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication
      carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance
      Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and
      standardized FreeSurfer image analysis, we found negative dose-response
      associations with copy number on intracranial volume and on regional caudate,
      pallidum and putamen volumes (beta = -0.71 to -1.37; P < 0.0005). In an
      independent sample, consistent results were obtained, with significant effects in
      the pallidum (beta = -0.95, P = 0.0042). The two data sets combined showed
      significant negative dose-response for the accumbens, caudate, pallidum, putamen
      and ICV (P = 0.0032, 8.9 * 10-6, 1.7 * 10-9, 3.5 * 10-12 and 1.0 * 10-4,
      respectively). Full scale IQ was lower in both deletion and duplication carriers
      compared to non-carriers. This is the first brain MRI study of the impact of the
      16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain
      structures, suggesting a neuropathological pattern underlying the
      neurodevelopmental syndromes.

PMID- 30283036
TI  - Intergenerational transmission of depression: clinical observations and molecular
      mechanisms.
AB  - Maternal mental illness can have a devastating effect during the perinatal
      period, and has a profound impact on the care that the baby receives and on the
      relationships that the baby forms. This review summarises clinical evidence
      showing the effects of perinatal depression on offspring physical and behavioural
      development, and on the transmission of psychopathology between generations. We
      then evaluate a number of factors which influence this relationship, such as
      genetic factors, the use of psychotropic medications during pregnancy, the timing
      within the perinatal period, the sex of the foetus, and exposure to maltreatment
      in childhood. Finally, we examine recent findings regarding the molecular
      mechanisms underpinning these clinical observations, and identify relevant
      epigenetic and biomarker changes in the glucocorticoid, oxytocin, oestrogen and
      immune systems, as key biological mediators of these clinical findings. By
      understanding these molecular mechanisms in more detail, we will be able to
      improve outcomes for both mothers and their offspring for generations.

PMID- 30283037
TI  - Adolescent exposure to Delta9-tetrahydrocannabinol alters the transcriptional
      trajectory and dendritic architecture of prefrontal pyramidal neurons.
AB  - Neuronal circuits within the prefrontal cortex (PFC) mediate higher cognitive
      functions and emotional regulation that are disrupted in psychiatric disorders.
      The PFC undergoes significant maturation during adolescence, a period when
      cannabis use in humans has been linked to subsequent vulnerability to psychiatric
      disorders such as addiction and schizophrenia. Here, we investigated in a rat
      model the effects of adolescent exposure to Delta9-tetrahydrocannabinol (THC), a
      psychoactive component of cannabis, on the morphological architecture and
      transcriptional profile of layer III pyramidal neurons-using cell type- and layer
      specific high-resolution microscopy, laser capture microdissection and next
      generation RNA-sequencing. The results confirmed known normal expansions in basal
      dendritic arborization and dendritic spine pruning during the transition from
      late adolescence to early adulthood that were accompanied by differential
      expression of gene networks associated with neurodevelopment in control animals.
      In contrast, THC exposure disrupted the normal developmental process by inducing
      premature pruning of dendritic spines and allostatic atrophy of dendritic
      arborization in early adulthood. Surprisingly, there was minimal overlap of the
      developmental transcriptomes between THC- and vehicle-exposed rats. THC altered
      functional gene networks related to cell morphogenesis, dendritic development,
      and cytoskeleton organization. Marked developmental network disturbances were
      evident for epigenetic regulators with enhanced co-expression of chromatin- and
      dendrite-related genes in THC-treated animals. Dysregulated PFC co-expression
      networks common to both the THC-treated animals and patients with schizophrenia
      were enriched for cytoskeletal and neurite development. Overall, adolescent THC
      exposure altered the morphological and transcriptional trajectory of PFC
      pyramidal neurons, which could enhance vulnerability to psychiatric disorders.

PMID- 30283039
TI  - Cold-season disasters on the Eurasian steppes: Climate-driven or man-made.
AB  - Socio-ecological damage from climate-related disasters has increased worldwide,
      including a type of cold-season disaster (dzud) that is unique to the Eurasian
      steppes, notably Mongolia. During 2000-2014, dzuds killed approximately 30
      million livestock and impacted the Mongolian socio-economy. The contributions of
      both natural and social processes to livestock mortality were not previously
      considered across Mongolia. Here, we consider the contribution of both multiple
      climate hazards (drought, cold temperatures and snow), and socioeconomic
      vulnerability (herders' livestock and coping-capacity) to mortality risk. We
      performed multi-regression analyses for each province using meteorological,
      livestock and socioeconomic datasets. Our results show that 93.5% of mortality
      within Mongolia was caused by a combination of multi-hazards (47.3%) and
      vulnerability (46.2%), suggesting dzuds were both climate- and man-made. However,
      in high-mortality hotspots, mortality was primarily caused by multi-hazards
      (drought-induced pasture deficiency and deep-snow). Livestock overpopulation and
      a lack of coping capacities that caused inadequate preparedness (e.g.,
      hay/forage) were the main vulnerability factors. Frequent and severe multi
      hazards greatly increased the mortality risk, while increased vulnerability
      caused by socioeconomic changes in Mongolia since the 1990s tended to amplify the
      effects of multi-hazards. Thus, reductions in herder vulnerability within high
      mortality hotspots would likely be an effective means of mitigating the risk of
      future dzuds.

PMID- 30283038
TI  - Combined impacts of deforestation and wildlife trade on tropical biodiversity are
      severely underestimated.
AB  - Tropical forest diversity is simultaneously threatened by habitat loss and
      exploitation for wildlife trade. Quantitative conservation assessments have
      previously considered these threats separately, yet their impacts frequently act
      together. We integrate forest extent maps in 2000 and 2015 with a method of
      quantifying exploitation pressure based upon a species' commercial value and
      forest accessibility. We do so for 308 forest-dependent bird species, of which 77
      are commercially traded, in the Southeast Asian biodiversity hotspot of
      Sundaland. We find 89% (274) of species experienced average habitat losses of 16%
      and estimate exploitation led to mean population declines of 37%. Assessing the
      combined impacts of deforestation and exploitation indicates the average losses
      of exploited species are much higher (54%), nearly doubling the regionally
      endemic species (from 27 to 51) threatened with extinction that should be IUCN
      Red Listed. Combined assessment of major threats is vital to accurately quantify
      biodiversity loss.

PMID- 30283040
TI  - Effect of statins on experimental postoperative adhesion: a systematic review and
      meta-analysis.
AB  - Adhesion is a significant concern after surgery. Many researchers studied the
      anti-adhesive effect of statin, of which results were inconsistent. Thus, we
      purposed to perform a systematic review and meta-analysis to evaluate the effect
      of statins on postoperative adhesion in an experimental study. A comprehensive
      search was conducted using MEDLINE, EMBASE, and Google Scholar to identify animal
      studies that investigated the postoperative anti-adhesive effect of statins
      applied at the surgical area. Primary outcome measure was gross adhesion score.
      Secondary outcomes included microscopic adhesion score and tissue plasminogen
      activator (t-PA) activity. Totally, 298 rats from 9 animal studies (172 rats
      received statin therapy and 126 rats received placebo or no treatment) were
      included in the final analysis. The combined results showed that gross and
      microscopic adhesion scores were significantly lower in the statin group in
      comparison to the control group (standardized mean difference [SMD] = 1.65, 95%
      confidence interval [CI]: 1.02 to 2.28, Pchi2 < 0.001, I2 = 77.9%; SMD = 1.90,
      95% CI: 1.10 to 2.79, Pchi2 < 0.001, I2 = 84.5%, respectively). However, there
      was no evidence of a difference in t-PA activity (SMD = -3.43, 95% CI: -7.95 to
      1.09, Pchi2 < 0.001, I2 = 95.5%). In conclusion, statins were effective in
      preventing postoperative adhesion, as assessed based on gross and microscopic
      adhesion scores in rats.

PMID- 30283041
TI  - Copper pollution exacerbates the effects of ocean acidification and warming on
      kelp microscopic early life stages.
AB  - Ocean warming (OW), ocean acidification (OA) and their interaction with local
      drivers, e.g., copper pollution, may negatively affect macroalgae and their
      microscopic life stages. We evaluated meiospore development of the kelps
      Macrocystis pyrifera and Undaria pinnatifida exposed to a factorial combination
      of current and 2100-predicted temperature (12 and 16  degrees C, respectively),
      pH (8.16 and 7.65, respectively), and two copper levels (no-added-copper and
      species-specific germination Cu-EC50). Meiospore germination for both species
      declined by 5-18% under OA and ambient temperature/OA conditions, irrespective of
      copper exposure. Germling growth rate declined by >40%.day-1, and gametophyte
      development was inhibited under Cu-EC50 exposure, compared to the no-added-copper
      treatment, irrespective of pH and temperature. Following the removal of copper
      and 9-day recovery under respective pH and temperature treatments, germling
      growth rates increased by 8-18%.day-1. The exception was U. pinnatifida under
      OW/OA, where growth rate remained at 10%.day-1 before and after copper exposure.
      Copper-binding ligand concentrations were higher in copper-exposed cultures of
      both species, suggesting that ligands may act as a defence mechanism of kelp
      early life stages against copper toxicity. Our study demonstrated that copper
      pollution is more important than global climate drivers in controlling meiospore
      development in kelps as it disrupts the completion of their life cycle.

PMID- 30283042
TI  - Human neural stem cell transplantation improves cognition in a murine model of
      Alzheimer's disease.
AB  - Stem cell transplantation offers a potentially transformative approach to
      treating neurodegenerative disorders. The safety of cellular therapies is
      established in multiple clinical trials, including our own in amyotrophic lateral
      sclerosis. To initiate similar trials in Alzheimer's disease, efficacious cell
      lines must be identified. Here, we completed a preclinical proof-of-concept study
      in the APP/PS1 murine model of Alzheimer's disease. Human neural stem cell
      transplantation targeted to the fimbria fornix significantly improved cognition
      in two hippocampal-dependent memory tasks at 4 and 16 weeks post-transplantation.
      While levels of synapse-related proteins and cholinergic neurons were unaffected,
      amyloid plaque load was significantly reduced in stem cell transplanted mice and
      associated with increased recruitment of activated microglia. In vitro, these
      same neural stem cells induced microglial activation and amyloid phagocytosis,
      suggesting an immunomodulatory capacity. Although long-term transplantation
      resulted in significant functional and pathological improvements in APP/PS1 mice,
      stem cells were not identified by immunohistochemistry or PCR at the study
      endpoint. These data suggest integration into native tissue or the idea that
      transient engraftment may be adequate for therapeutic efficacy, reducing the need
      for continued immunosuppression. Overall, our results support further preclinical
      development of human neural stem cells as a safe and effective therapy for
      Alzheimer's disease.

PMID- 30283043
TI  - Closing water productivity gaps to achieve food and water security for a global
      maize supply.
AB  - To achieve food and water security, it is as important to close the water
      productivity (WP) gap (which was defined as the difference between the maximum
      attainable WP and the currently achieved WP at the field scale) as it is to close
      yield gaps. However, few studies have provided quantitative estimates of existing
      WP gaps and constraining factors for global maize production. Using a meta
      analysis of 473 published studies covering 31 countries and 5,553 observations
      (932 site-years), we found the global average WP value for irrigated maize was
      18.6 kg ha-1 mm-1. These WPs varied by factors such as seasonal precipitation,
      irrigation regimes, soil organic matter and soil pH. In current production
      systems, there exists a huge scope for improvement in maize WP, but the reported
      field experiments achieved only 20-46% of potential WP across all countries.
      Considering the future, raising WP to 85% of potential WP by 2050, a 100%
      increase in maize production could be achieved with 20% less planted area and 21%
      less water consumption than in 2005. Closing the WP gap may be critical to
      ensuring food security and achieving sustainable global agriculture.

PMID- 30283044
TI  - Tobacco smoking and the risk of abdominal aortic aneurysm: a systematic review
      and meta-analysis of prospective studies.
AB  - Several studies have found that smoking increases the risk of abdominal aortic
      aneurysm, however, the strength of the association has differed between studies
      and data from cohort studies have not yet been summarized. A systematic review
      and meta-analysis was therefore conducted to clarify this association. We
      searched PubMed and Embase databases up to May 2nd 2018. A random effects model
      was used to estimate summary relative risks (RRs) and 95% confidence intervals
      (CIs). Twenty three prospective studies were included. Comparing current, former
      and ever smokers with never smokers the summary RRs were 4.87 (95% CI: 3.93-6.02,
      I2 = 92%, n = 20), 2.10 (95% CI: 1.76-2.50, I2 = 71%, n = 15) and 3.28 (95% CI:
      2.60-4.15, I2 = 96%, n = 18), respectively. The summary RR was 1.87 (95% CI: 1.45
      2.40, I2 = 97%) per 10 cigarettes per day, 1.78 (95% CI: 1.54-2.06, I2 = 83%) per
      10 pack-years was and 0.45 (95% CI: 0.32-0.63, I2 = 92.3%) per 10 years of
      smoking cessation. There was evidence of nonlinearity for cigarettes per day and
      pack-years (pnonlinearity < 0.0001 and pnonlinearity = 0.02, respectively), but
      not for smoking cessation, pnonlinearity = 0.85. Among smokers who quit, the RR
      was similar to that of never smokers by 25 years of smoking cessation. These
      findings confirm a strong association between smoking and the risk of developing
      abdominal aortic aneurysms.

PMID- 30283045
TI  - Influence of ylHog1 MAPK kinase on Yarrowia lipolytica stress response and
      erythritol production.
AB  - Erythritol production is a unique response to hyperosmotic stress that is
      observed in a small group of yeasts, including Yarrowia lipolytica. This study
      investigated whether this unusual mechanism is regulated by the HOG pathway, well
      described in Saccharomyces cerevisiae. The gene YALI0E25135g was identified as
      the Y. lipolytica homologue of HOG1 and was found to be phosphorylated in
      response to hyperosmotic shock. Deletion of the gene caused a significant
      decrease in resistance to hyperosmotic stress and negatively affected erythritol
      production. Interestingly, the deletion strain yl-hog1Delta displayed significant
      morphological defects, with the cells growing in a filamentous form. Moreover, yl
      hog1Delta cells were also resistant to the cell wall damaging agents Congo red
      and calcofluor white. Collectively, these results indicate that yl-Hog1 is
      crucial for the cellular response to hyperosmotic stress, plays a role in the
      induction of erythritol production, and potentially prevents cross-talk with
      different MAPK signalling pathways in the cell.

PMID- 30283046
TI  - Impaired platelet activity and hypercoagulation in healthy term and moderately
      preterm newborns during the early neonatal period.
AB  - BACKGROUND: Preterm newborns are at thrombohemorrhagic risk during the early
      neonatal period. Taking into account the lack of informative tools for the
      laboratory diagnosis of hemostasis disorders in newborns, our goal was to
      determine the baseline values of thrombodynamics and platelet functional activity
      in healthy term and moderately preterm newborns during the early neonatal period
      future potential clinical use of these tests. METHODS: Coagulation was assessed
      using an integral assay of thrombodynamics and standard coagulation assays, and
      platelet functional activity was estimated by flow cytometry. RESULTS:
      Hypercoagulation of newborns, represented by a significantly higher clot growth
      velocity and the presence of spontaneous clots in the thrombodynamics, was
      combined with platelet hypoactivity. Granule release, phosphatidylserine
      exposure, and the ability to change shape upon activation were decreased in the
      platelets of moderately preterm newborns. The platelet function remained at the
      same level over the first four days of life, whereas the hypercoagulation became
      less pronounced. CONCLUSIONS: The hemostasis of newborns is characterized by
      hypercoagulation combined with reduced platelet functional activity. Moderately
      preterm and term newborns do not differ in the parameters of coagulation, while
      some of the functional responses of platelets are lower in moderately preterm
      newborns than in term.

PMID- 30283047
TI  - The contribution of the gut microbiome to neurodevelopment and neuropsychiatric
      disorders.
AB  - Bidirectional communication between the gut and brain is well recognized, with
      data now accruing for a specific role of the gut microbiota in that link,
      referred to as the microbiome-gut-brain axis. This review will discuss the
      emerging role of the gut microbiota in brain development and behavior. Animal
      studies have clearly demonstrated effects of the gut microbiota on gene
      expression and neurochemical metabolism impacting behavior and performance. Based
      on these changes, a modulating role of the gut microbiota has been demonstrated
      for a variety of neuropsychiatric disorders, including depression, anxiety, and
      movement including Parkinson's, and importantly for the pediatric population
      autism. Critical developmental windows that influence early behavioral outcomes
      have been identified that include both the prenatal environment and early
      postnatal colonization periods. The clearest data regarding the role of the gut
      microbiota on neurodevelopment and psychiatric disorders is from animal studies;
      however, human data have begun to emerge, including an association between early
      colonization patterns and cognition. The importance of understanding the
      contribution of the gut microbiota to the development and functioning of the
      nervous system lies in the potential to intervene using novel microbial-based
      approaches to treating neurologic conditions. While pathways of communication
      between the gut and brain are well established, the gut microbiome is a new
      component of this axis. The way in which organisms that live in the gut influence
      the central nervous system (CNS) and host behavior is likely to be multifactorial
      in origin. This includes immunologic, endocrine, and metabolic mechanisms, all of
      which are pathways used for other microbial-host interactions. Germ-free (GF)
      mice are an important model system for understanding the impact of gut microbes
      on development and function of the nervous system. Alternative animal model
      systems have further clarified the role of the gut microbiota, including
      antibiotic treatment, fecal transplantation, and selective gut colonization with
      specific microbial organisms. Recently, researchers have started to examine the
      human host as well. This review will examine the components of the CNS
      potentially influenced by the gut microbiota, and the mechanisms mediating these
      effects. Links between gut microbial colonization patterns and host behavior
      relevant to a pediatric population will be examined, highlighting important
      developmental windows in utero or early in development.

PMID- 30283048
TI  - In Memoriam Prof. Dr. Dr. h.c. Klaus Philipp Riegel-Leading Pediatrician,
      Clinical Scientist, and Pioneer Perinatal Epidemiologist.

PMID- 30283049
TI  - Is robot-assisted surgery noninferior or real progress?

PMID- 30283050
TI  - The challenges of supporting male infertility treatment in South Africa.

PMID- 30283051
TI  - A Dexterous, Glove-Based Teleoperable Low-Power Soft Robotic Arm for Delicate
      Deep-Sea Biological Exploration.
AB  - Modern marine biologists seeking to study or interact with deep-sea organisms are
      confronted with few options beyond industrial robotic arms, claws, and suction
      samplers. This limits biological interactions to a subset of "rugged" and mostly
      immotile fauna. As the deep sea is one of the most biologically diverse and least
      studied ecosystems on the planet, there is much room for innovation in
      facilitating delicate interactions with a multitude of organisms. The
      biodiversity and physiology of shallow marine systems, such as coral reefs, are
      common study targets due to the easier nature of access; SCUBA diving allows for
      in situ delicate human interactions. Beyond the range of technical SCUBA (~150
      m), the ability to achieve the same level of human dexterity using robotic
      systems becomes critically important. The deep ocean is navigated primarily by
      manned submersibles or remotely operated vehicles, which currently offer few
      options for delicate manipulation. Here we present results in developing a soft
      robotic manipulator for deep-sea biological sampling. This low-power glove
      controlled soft robot was designed with the future marine biologist in mind,
      where science can be conducted at a comparable or better means than via a human
      diver and at depths well beyond the limits of SCUBA. The technology relies on
      compliant materials that are matched with the soft and fragile nature of marine
      organisms, and uses seawater as the working fluid. Actuators are driven by a
      custom proportional-control hydraulic engine that requires less than 50 W of
      electrical power, making it suitable for battery-powered operation. A wearable
      glove master allows for intuitive control of the arm. The manipulator system has
      been successfully operated in depths exceeding 2300 m (3500 psi) and has been
      field-tested onboard a manned submersible and unmanned remotely operated
      vehicles. The design, development, testing, and field trials of the soft
      manipulator is placed in context with existing systems and we offer suggestions
      for future work based on these findings.

PMID- 30283052
TI  - Monitoring of microbial dynamics in a drinking water distribution system using
      the culture-free, user-friendly, MYcrobiota platform.
AB  - Drinking water utilities currently rely on a range of microbiological detection
      techniques to evaluate the quality of their drinking water (DW). However,
      microbiota profiling using culture-free 16S rRNA gene next-generation sequencing
      (NGS) provides an opportunity for improved monitoring of the microbial ecology
      and quality of DW. Here, we evaluated the utility of a previously validated
      microbiota profiling platform (MYcrobiota) to investigate the microbial dynamics
      of a full-scale, non-chlorinated DW distribution system (DWDS). In contrast to
      conventional methods, we observed spatial and temporal bacterial genus changes
      (expressed as operational taxonomic units - OTUs) within the DWDS. Further, a
      small subset of bacterial OTUs dominated with abundances that shifted across the
      length of the DWDS, and were particularly affected by a post-disinfection step.
      We also found seasonal variation in OTUs within the DWDS and that many OTUs could
      not be identified, even though MYcrobiota is specifically designed to reduce
      potential PCR sequencing artefacts. This suggests that our current knowledge
      about the microbial ecology of DW communities is limited. Our findings
      demonstrate that the user-friendly MYcrobiota platform facilitates culture-free,
      standardized microbial dynamics monitoring and has the capacity to facilitate the
      introduction of microbiota profiling into the management of drinking water
      quality.

PMID- 30283053
TI  - Rapid in situ synthesis of polymer-metal nanocomposite films in several seconds
      using a CO2 laser.
AB  - We demonstrate the rapid in situ synthesis of polymer-metal nanocomposite films
      using a CO2 laser at 10.6 MUm. The mechanism of our method is that the precursor
      of the metal nanoparticles, i.e., the metallic ions, is very rapidly reduced in
      the laser-heated polymer matrix without any reducing agent. Unlike other known
      laser-induced reduction methods using UV lasers, which produce radicals to
      promote reduction, the CO2 laser energy is mainly absorbed by the glass
      substrate, and the laser-heated substrate heats the polymer matrix through heat
      diffusion to promote reduction. The superiority of the use of CO2 lasers over
      nanosecond visible~UV lasers is also demonstrated in terms of the damage to the
      film. The developed method can be a new alternative to quickly synthesize a
      variety of polymer-metal nanocomposite films.

PMID- 30283054
TI  - Author Correction: A comparison of tools for the simulation of genomic next
      generation sequencing data.
AB  - The originally published article contained errors in Fig. 1 (Decision tree for
      the selection of a suitable NGS genomic simulator), whereby the labels 'Variants'
      and 'No Variants' had been switched. The correct figure is presented in this
      notice.

PMID- 30283055
TI  - The importance of genetic counselling in genome-wide sequencing.

PMID- 30283056
TI  - Antarctic marine ciliates under stress: superoxide dismutases from the
      psychrophilic Euplotes focardii are cold-active yet heat tolerant enzymes.
AB  - Oxidative stress is a particularly severe threat to Antarctic marine polar
      organisms because they are exposed to high dissolved oxygen and to intense UV
      radiation. This paper reports the features of three superoxide dismutases from
      the Antarctic psychrophilic ciliate Euplotes focardii that faces two
      environmental challenges, oxidative stress and low temperature. Two out of these
      are Cu,Zn superoxide dismutases (named Ef-SOD1a and Ef-SOD1b) and one belongs to
      the Mn-containing group (Ef-SOD2). Ef-SOD1s and Ef-SOD2 differ in their
      evolutionary history, expression and overall structural features. Ef-SOD1 genes
      are expressed at different levels, with Ef-SOD1b mRNA 20-fold higher at the
      ciliate optimal temperature of growth (4  degrees C). All Ef-SOD enzymes are
      active at 4  degrees C, consistent with the definition of cold-adapted enzymes.
      At the same time, they display temperatures of melting in the range 50-70 
      degrees C and retain residual activity after incubation at 65-75  degrees C.
      Supported by data of molecular dynamics simulation, we conclude that the E.
      focardii SODs combine cold activity, local molecular flexibility and thermo
      tolerance.

PMID- 30283057
TI  - Kidney-derived c-kit+ progenitor/stem cells contribute to podocyte recovery in a
      model of acute proteinuria.
AB  - Kidney-derived c-kit+ cells exhibit progenitor/stem cell properties and can
      regenerate epithelial tubular cells following ischemia-reperfusion injury in
      rats. We therefore investigated whether c-kit+ progenitor/stem cells contribute
      to podocyte repair in a rat model of acute proteinuria induced by puromycin
      aminonucleoside (PAN), the experimental prototype of human minimal change disease
      and early stages of focal and segmental glomerulosclerosis. We found that c-kit+
      progenitor/stem cells accelerated kidney recovery by improving foot process
      effacement (foot process width was lower in c-kit group vs saline treated
      animals, P = 0.03). In particular, these cells engrafted in small quantity into
      tubules, vessels, and glomeruli, where they occasionally differentiated into
      podocyte-like cells. This effect was related to an up regulation of alpha-Actinin
      4 and mTORC2-Rictor pathway. Activation of autophagy by c-kit+ progenitor/stem
      cells also contributed to kidney regeneration and intracellular homeostasis
      (autophagosomes and autophagolysosomes number and LC3A/B-I and LC3A/B-II
      expression were higher in the c-kit group vs saline treated animals, P = 0.0031
      and P = 0.0009, respectively). Taken together, our findings suggest that kidney
      derived c-kit+ progenitor/stem cells exert reparative effects on glomerular
      disease processes through paracrine effects, to a lesser extent differentiation
      into podocyte-like cells and contribution to maintenance of podocyte cytoskeleton
      after injury. These findings have clinical implications for cell therapy of
      glomerular pathobiology.

PMID- 30283058
TI  - Voice-selective prediction alterations in nonclinical voice hearers.
AB  - Auditory verbal hallucinations (AVH) are a cardinal symptom of psychosis but also
      occur in 6-13% of the general population. Voice perception is thought to engage
      an internal forward model that generates predictions, preparing the auditory
      cortex for upcoming sensory feedback. Impaired processing of sensory feedback in
      vocalization seems to underlie the experience of AVH in psychosis, but whether
      this is the case in nonclinical voice hearers remains unclear. The current study
      used electroencephalography (EEG) to investigate whether and how hallucination
      predisposition (HP) modulates the internal forward model in response to self
      initiated tones and self-voices. Participants varying in HP (based on the Launay
      Slade Hallucination Scale) listened to self-generated and externally generated
      tones or self-voices. HP did not affect responses to self vs. externally
      generated tones. However, HP altered the processing of the self-generated voice:
      increased HP was associated with increased pre-stimulus alpha power and increased
      N1 response to the self-generated voice. HP did not affect the P2 response to
      voices. These findings confirm that both prediction and comparison of predicted
      and perceived feedback to a self-generated voice are altered in individuals with
      AVH predisposition. Specific alterations in the processing of self-generated
      vocalizations may establish a core feature of the psychosis continuum.

PMID- 30283059
TI  - Cationic clustering influences the phase behaviour of ionic liquids.
AB  - "Unlike charges attract, but like charges repel". This conventional wisdom has
      been recently challenged for ionic liquids. It could be shown that like-charged
      ions attract each other despite the powerful opposing electrostatic forces. In
      principle, cooperative hydrogen bonding between ions of like-charge can overcome
      the repulsive Coulomb interaction while pushing the limits of chemical bonding.
      The key challenge of this solvation phenomenon is to establish design principles
      for the efficient formation of clusters of like-charged ions in ionic liquids.
      This is realised here for a set of well-suited ionic liquids including the same
      hydrophobic anion but different cations all equipped with hydroxyethyl groups for
      possible H-bonding. The formation of H-bonded cationic clusters can be controlled
      by the delocalization of the positive charge on the cations. Strongly localized
      charge results in cation-anion interaction, delocalized charge leads to the
      formation of cationic clusters. For the first time we can show, that the cationic
      clusters influence the properties of ILs. ILs comprising these clusters can be
      supercooled and form glasses. Crystalline structures are obtained only, if the
      ILs are dominantly characterized by the attraction between opposite-charged ions
      resulting in conventional ion pairs. That may open a new path for controlling
      glass formation and crystallization. The glass temperatures and the phase
      transitions of the ILs are observed by differential scanning calorimetry (DSC)
      and infrared (IR) spectroscopy.

PMID- 30283060
TI  - Turning a native or corroded Mg alloy surface into an anti-corrosion coating in
      excited CO2.
AB  - Despite their energy-efficient merits as promising light-weight structural
      materials, magnesium (Mg) based alloys suffer from inadequate corrosion
      resistance. One primary reason is that the native surface film on Mg formed in
      air mainly consists of Mg(OH)2 and MgO, which is porous and unprotective,
      especially in humid environments. Here, we demonstrate an environmentally benign
      method to grow a protective film on the surface of Mg/Mg alloy samples at room
      temperature, via a direct reaction of already-existing surface film with excited
      CO2. Moreover, for samples that have been corroded obviously on surface, the
      corrosion products can be converted directly to create a new protective surface.
      Mechanical tests show that compared with untreated samples, the protective layer
      can elevate the yield stress, suppress plastic instability and prolong
      compressive strains without peeling off from the metal surface. This
      environmentally friendly surface treatment method is promising to protect Mg
      alloys, including those already-corroded on the surface.

PMID- 30283061
TI  - Longitudinal changes in physical capacity from adolescence to middle age in men
      and women.
AB  - The aim was to investigate how physical capacity changes from adolescence through
      early adulthood to middle age with focus on early aging. The aim was also to
      study if physical capacity in middle age could be predicted by factors in
      adolescence or early adulthood. A cohort of men and women in Sweden (SPAF-1958, n
      = 425) have been followed for 36 years, at 16, 34, and 52 years of age. The study
      includes, among other variables, objective measures of physical capacity. At age
      52, 50% of the original cohort participated in exercise testing. Physical
      capacity increased from 16 to 34 years. From 34 to 52 years, physical capacity
      decreased in both genders by 15-20% in all but one test. Physical capacity at 16
      and 34 years of age were better predictors of physical capacity at age 52 than
      body dimensions, school grades and life style factors. In conclusion, present
      data confirm earlier cross-sectional studies regarding the decrease in aerobic
      capacity and muscular strength during the early ageing period in both genders.
      The study has also generated novel data that show a smaller decline in muscular
      endurance than previously reported. Finally, physical capacity is fairly stable
      from adolescence to middle age.

PMID- 30283063
TI  - 3D printing aids transplantation planning.

PMID- 30283064
TI  - Augmenting GPS IWV estimations using spatio-temporal cloud distribution extracted
      from satellite data.
AB  - Water vapor (WV) is the most variable greenhouse gas in the troposphere,
      therefore investigation of its spatio-temporal distribution and motion is of
      great importance in meteorology and climatology studies. Here, we suggest a new
      strategy for augmenting integrated water vapor (IWV) estimations using both
      remote sensing satellites and global positioning system (GPS) tropospheric path
      delays. The strategy is based first on the ability to estimate METEOSAT-10 7.3 um
      WV pixel values by extracting the mathematical dependency between the IWV amount
      calculated from GPS zenith wet delays (ZWD) and the METEOSAT-10 data. We then use
      the surface temperature differences between ground station measurements and
      METEOSAT-10 10.8 um infra-red (IR) channel to identify spatio-temporal cloud
      distribution structures. As a last stage, the identified cloud features are
      mapped into the GPS-IWV distribution map when preforming the interpolation
      between adjusted GPS station inside the network. The suggested approach improves
      the accuracy of estimated regional IWV maps, in comparison with radiosonde data,
      thus enables to obtain the total water amount at the atmosphere, both in the form
      of clouds and vapor. Mean and root mean square (RMS) difference between the GPS
      IWV estimations, using the spatio-temporal clouds distribution, and radiosonde
      data are reduced from 1.77 and 2.81 kg/m2 to 0.74 and 2.04 kg/m2, respectively.
      Furthermore, by improving the accuracy of the estimated regional IWV maps
      distribution it is possible to increase the accuracy of regional Numerical
      Weather Prediction (NWP) platforms.

PMID- 30283065
TI  - Towards improvement in prediction of iodine value in edible oil system based on
      chemometric analysis of portable vibrational spectroscopic data.
AB  - Iodine value (IV) is a significant parameter to illustrate the quality of edible
      oil. In this study, three portable spectroscopy devices were employed to
      determine IV in mixed edible oil system, a new Micro-Electro-Mechanical-System
      (MEMS) Fourier Transform Infrared Spectrometer (MEMS-FTIR), a MicroNIRTM1700 and
      an i-Raman Plus-785S. Quantitative model was built by Partial least squares (PLS)
      regression model and four variable selection methods were applied before PLS
      model, which are Monte Carlo uninformative variables elimination (MCUVE),
      competitive reweighted sampling (CARS), bootstrapping soft shrinkage approach
      (BOSS) and variable combination population analysis (VCPA). The coefficient of
      determination (R2), and the root mean square error prediction (RMSEP) were used
      as indicators for the predictability of the PLS models. In MicroNIRTM1700
      dataset, MCUVE gave the lowest RMSEP (2.3440), in MEMS-FTIR dataset, CARS showed
      the best performance with RMSEP (2.2185), in i-Raman Plus-785S dataset, BOSS gave
      the lowest RMSEP (2.5058). They all had great improvements than full spectrum PLS
      model. Four variable selection methods take a smaller number of variables and
      perform significant superiority in prediction accuracy. It was demonstrated that
      three new portable instruments would be suitable for the on-site determination of
      edible oil quality in infrared and Raman field.

PMID- 30283066
TI  - Visualization of perforin/gasdermin/complement-formed pores in real cell
      membranes using atomic force microscopy.
AB  - Different types of pores ubiquitously form in cell membranes, leading to various
      types of cell death that profoundly influence the fate of inflammation and the
      disease status. However, these pores have never truly been visualized to date.
      Atomic force microscopy (AFM), which is emerging as a powerful tool to analyze
      the mechanical properties of biomolecules and cells, is actually an excellent
      imaging platform that allows biological samples to be visualized by probing
      surface roughness at the level of atomic resolution. Here, membrane pore
      structures were clearly visualized using AFM. This visualization not only
      describes the aperture and depth of the pore complexes but also highlights
      differences among the pores formed by perforin and gasdermins in tumor cell
      membranes and by complement in immune cell membranes. Additionally, this type of
      visualization also reveals the dynamic process of pore formation, fusion, and
      repair.

PMID- 30283067
TI  - A critical look at "Energy savings, emissions reductions, and health co-benefits
      of the green building movement".
AB  - MacNaughton et al. recently published an article entitled, "Energy savings,
      emissions reductions, and health co-benefits of the green building movement" in
      which they claim to calculate the environmental co-benefits associated with the
      (assumed) reduced energy use of green buildings. They consider only LEED
      (Leadership in Energy and Environmental Design) commercial buildings and make two
      fundamental assumptions: (1) that each LEED building, year after year, achieves
      the energy savings projected by its design team, and (2) that the fuel mix of
      LEED buildings is the same as the average mix for other buildings in the same
      geographic region.Here we show that these assumptions are not supported by data.
      Numerous studies have shown that buildings, on average, use significantly more
      energy than projected by design simulations. Furthermore, a decade of research
      suggests that LEED-certified buildings, on average, achieve little or no primary
      energy savings relative to other similar buildings. In addition, evidence
      suggests that any reduction in site energy is typically achieved through
      increased electric use and corresponding off-site energy loss. The environmental
      benefits of LEED buildings calculated by MacNaughton et al. have dubious value
      because they are based on assumptions that are inconsistent with measured LEED
      building energy performance.

PMID- 30283062
TI  - A rust fungal effector binds plant DNA and modulates transcription.
AB  - The basidiomycete Melampsora larici-populina causes poplar rust disease by
      invading leaf tissues and secreting effector proteins through specialized
      infection structures known as haustoria. The mechanisms by which rust effectors
      promote pathogen virulence are poorly understood. The present study characterized
      Mlp124478, a candidate effector of M. larici-populina. We used the models
      Arabidopsis thaliana and Nicotiana benthamiana to investigate the function of
      Mlp124478 in plant cells. We established that Mlp124478 accumulates in the
      nucleus and nucleolus, however its nucleolar accumulation is not required to
      promote growth of the oomycete pathogen Hyaloperonospora arabidopsidis. Stable
      constitutive expression of Mlp124478 in A. thaliana repressed the expression of
      genes involved in immune responses, and also altered leaf morphology by
      increasing the waviness of rosette leaves. Chip-PCR experiments showed that
      Mlp124478 associats'e with the TGA1a-binding DNA sequence. Our results suggest
      that Mlp124478 exerts a virulence activity and binds the TGA1a promoter to
      suppress genes induced in response to pathogen infection.

PMID- 30283068
TI  - Measuring environmental noise from airports, oil and gas operations, and traffic
      with smartphone applications: laboratory and field trials.
AB  - Environmental noise from sources such as traffic, airports, and oil and gas (O&G)
      operations is associated with nuisance and health concerns. Smartphones with
      external microphones have been recommended for environmental noise monitoring and
      may be useful tools for citizen science, but are not validated against reference
      methods. We evaluated laboratory performance of three smartphone/application
      (app) configurations recommended for environmental noise measurement. Two
      smartphone/app configurations were also compared to a reference sampler, a type 1
      sound level meter (SLM) at ten outdoor sites with traffic, airport, and O&G
      noise. To evaluate performance, we compared the mean squared error, variance,
      bias, and Krippendorff's Alpha by smartphone/app combination and testing location
      for both audible (A-weighted) and low-frequency (C-weighted) noise. We observed
      that laboratory measurements were in strong agreement with a reference sampler.
      The field A-weighted noise level results had strong agreement with the SLM at
      several outdoor sites, but our C-weighted noise results ranged from moderate to
      substantial agreement. For our tested configurations, we find that smartphones
      with external microphones are reliable proxies for measuring A- and C-weighted
      noise in a laboratory setting. Outdoor performance depends on noise source type,
      weighting, and precision and accuracy needs of the investigation.

PMID- 30283069
TI  - Heat waves in South Korea: differences of heat wave characteristics by thermal
      indices.
AB  - Heat wave warning systems and related research define heat waves using various
      indices and there exists no standard definition for a heat wave. Despite various
      weather forecast services for heat stress in South Korea, it is unclear how
      different thermal indices affect the designation of heat waves and health effect
      estimates. We aimed to analyze trends of heat wave characteristics and mortality
      associations using various criteria for the warm season (June-September) in 2011
      5 for the most populated two cities in South Korea, Seoul and Busan. Hourly
      weather monitoring data and daily mortality data in each city were obtained. The
      following indices were estimated to define heat waves: air temperature, heat
      index (HI), humidex, apparent temperature (AT), effective temperature (ET), and
      wet-bulb globe temperature (WBGT). The thresholds of each index for heat wave
      definitions were obtained by statistical distribution (95th percentiles) and
      minimum mortality temperature (MMT). Thermal indices showed clustering of
      accumulation of excess heat above thresholds for northeast regions in the cities
      while air temperature showed it for central regions. Compared to 95th
      percentiles, the MMTs resulted 14 times longer heat wave days for thermal indices
      except for air temperature. When MMTs were used, nine times larger excess
      mortality from heat waves occurred for all indices compared to that from heat
      waves defined by the 95th percentiles. The thermal indices with the highest
      association between heat and mortality varied between the two cities: air
      temperature for Seoul and WBGT for Busan. Heat wave warnings should be based on a
      thorough comparison of how different heat wave criteria will affect the public
      health impact of heat wave warnings in terms of identifying a heat wave and
      degree of health impacts due to it.

PMID- 30283070
TI  - Reconfigurable MEMS Fano metasurfaces with multiple-input-output states for logic
      operations at terahertz frequencies.
AB  - A broad range of dynamic metasurfaces has been developed for manipulating the
      intensity, phase and wavefront of electromagnetic radiation from microwaves to
      optical frequencies. However, most of these metasurfaces operate in single-input
      output state. Here, we experimentally demonstrate a reconfigurable MEMS Fano
      resonant metasurface possessing multiple-input-output (MIO) states that performs
      logic operations with two independently controlled electrical inputs and an
      optical readout at terahertz frequencies. The far-field behaviour of Fano
      resonance exhibits XOR and XNOR operations, while the near-field resonant
      confinement enables the NAND operation. The MIO configuration resembling
      hysteresis-type closed-loop behaviour is realized through inducing
      electromechanically tuneable out-of-plane anisotropy in the near-field coupling
      of constituent resonator structures. The XOR metamaterial gate possesses
      potential applications in cryptographically secured terahertz wireless
      communication networks. Furthermore, the MIO features could lay the foundation
      for the realization of programmable and randomly accessible metamaterials with
      enhanced electro-optical performance across terahertz, infrared and optical
      frequencies.

PMID- 30283071
TI  - Impaired tumor growth and angiogenesis in mice heterozygous for Vegfr2 (Flk1).
AB  - VEGF signaling through its tyrosine kinase receptor, VEGFR2 (FLK1), is critical
      for tumor angiogenesis. Previous studies have identified a critical gene dosage
      effect of VegfA in embryonic development and vessel homeostasis,
      neovascularization, and tumor growth, and potent inhibitors of VEGFR2 have been
      used to treat a variety of cancers. Inhibition of FGFR signaling has also been
      considered as an antiangiogenic approach to treat a variety of cancers.
      Inhibition of VEGFR2 with neutralizing antibodies or with pharmacological
      inhibitors of the VEGFR tyrosine kinase domain has at least short-term efficacy
      with some cancers; however, also affects vessel homeostasis, leading to adverse
      complications. We investigate gene dosage effects of Vegfr2, Fgfr1, and Fgfr2 in
      three independent mouse models of tumorigenesis: two-stage skin chemical
      carcinogenesis, and sub-cutaneous transplantation of B16F0 melanoma and Lewis
      Lung Carcinoma (LLC). Mice heterozygous for Vegfr2 display profound defects in
      supporting tumor growth and angiogenesis. Unexpectedly, additional deletion of
      endothelial Fgfr1 and Fgfr2 in Vegfr2 heterozygous mice shows similar tumor
      growth and angiogenesis as the Vegfr2 heterozygous mice. Notably, hematopoietic
      deletion of two alleles of Vegfr2 had minimal impact on tumor growth, with little
      effect on angiogenesis, reinforcing the importance of endothelial Vegfr2
      heterozygosity. These studies reveal previously unrecognized Vegfr2 gene dosage
      effects in tumor angiogenesis and a lack of synergy between VEGFR2 and
      endothelial FGFR1/2 signaling during tumor growth.

PMID- 30283072
TI  - Spatial and temporal characteristics of temperature effects on cardiovascular
      disease in Southern China using the Empirical Mode Decomposition method.
AB  - Until now, few studies have analyzed the effects of temperature on cardiovascular
      disease (CVD) death at different time points. In this study, we chose 9 different
      cities in the subtropical and tropical areas of China and analyzed the
      correlation between temperature at different time points and CVD mortality. We
      completed this study in two steps. First, we analyzed different time trend
      decomposition data related to CVD mortality in different populations within the 9
      selected cities using empirical mode decomposition (EMD). Second, we created a
      regression fitting analysis of CVD mortality and temperatures at different time
      periods. The results showed that the CVD mortality of subtropical and tropical
      areas in southern Chinese cities represented spatial heterogeneity. The CVD
      mortality rates in Beihai, Hefei and Nanning showed rising trends, whereas the
      CVD mortality rates in Haikou, Guilin and Changde appeared to be decreasing. At
      the daily, seasonal and year time scales, low temperatures were negatively
      correlated with CVD mortality. Other than at the daily time scale, high
      temperatures did not significantly influence CVD mortality. This article will
      help to develop appropriate measures to reduce temperature-related mortality risk
      in different populations within the subtropical and tropical regions of China.

PMID- 30283074
TI  - STAT3's true colours.

PMID- 30283075
TI  - Editorial Comment: Long-term outcome after grafting with small intestinal
      submucosa and collagen fleece in patients with Peyronie's disease-a matched pair
      analysis.

PMID- 30283073
TI  - A Comparative Study of Hummingbirds and Chickens Provides Mechanistic Insight on
      the Histidine Containing Dipeptide Role in Skeletal Muscle Metabolism.
AB  - Histidine containing dipeptides (HCDs) have numerous ergogenic and therapeutic
      properties, but their primary role in skeletal muscle remains unclear. Potential
      functions include pH regulation, protection against reactive oxygen/nitrogen
      species, or Ca2+ regulation. In recognition of the challenge of isolating
      physiological processes in-vivo, we employed a comparative physiology approach to
      investigate the primary mechanism of HCD action in skeletal muscle. We selected
      two avian species (i.e., hummingbirds and chickens), who represented the extremes
      of the physiological processes in which HCDs are likely to function. Our findings
      indicate that HCDs are non-essential to the development of highly oxidative and
      contractile muscle, given their very low content in hummingbird skeletal tissue.
      In contrast, their abundance in the glycolytic chicken muscle, indicate that they
      are important in anaerobic bioenergetics as pH regulators. This evidence provides
      new insights on the HCD role in skeletal muscle, which could inform widespread
      interventions, from health to elite performance.

PMID- 30283076
TI  - Impact of overweight, obesity and severe obesity on life expectancy of Australian
      adults.
AB  - BACKGROUND/OBJECTIVES: Adult obesity has been shown to substantially heighten the
      risk of adverse health outcomes but its impact on life expectancy (LE) has not
      been quantified in Australia. Our aim is to estimate reductions in LE and years
      of life lost (YLL) associated with overweight and obesity, relative to those at a
      healthy weight for Australian adults aged 20-69 years. SUBJECTS/METHODS: We used
      a microsimulation model of obesity progression in Australia that integrates
      annual change in BMI based on age and sex, with Australian life-table data and
      published relative risk of all-cause mortality for different BMI categories.
      Remaining LE and YLL compared to healthy weight were estimated using 10-year
      cohorts, by sex. A nationally representative sample of 12,091 adults aged 20-69
      from the 2014/15 Australian National Health Survey were used to represent the
      input population of 14.9 million. RESULTS: Estimated remaining years of LE for
      healthy weight men and women aged 20-29 years was approximately 57.0 (95% CI 56.7
      57.4) and 59.7 (95% CI 59.4-60.0) years, respectively. YLL associated with being
      overweight at baseline was approximately 3.3 years. For those obese and severely
      obese the loss in LE was predicted to be 5.6-7.6 years and 8.1-10.3 years for men
      and women aged 20-29 years, respectively. Across men and women, excess BMI in the
      adult population is responsible for approximately 36.3 million YLLs. Men stand to
      lose 27.7% more life years compared to women. CONCLUSIONS: Overweight and obesity
      is associated with premature mortality at all ages, for both men and women.
      Adults aged 20-39 years with severe obesity will experience the largest YLL,
      relative to healthy weight. More needs to be done in Australia to establish a
      coherent, sustained, cost-effective strategy to prevent overweight and obesity,
      particularly for men in early adulthood.

PMID- 30283077
TI  - Ascorbic acid inhibits visceral obesity and nonalcoholic fatty liver disease by
      activating peroxisome proliferator-activated receptor alpha in high-fat-diet-fed
      C57BL/6J mice.
AB  - BACKGROUND/OBJECTIVES: Ascorbic acid is a known cofactor in the biosynthesis of
      carnitine, a molecule that has an obligatory role in fatty acid oxidation. Our
      previous studies have demonstrated that obesity is regulated effectively through
      peroxisome proliferator-activated receptor alpha (PPARalpha)-mediated fatty acid
      beta-oxidation. Thus, this study aimed to determine whether ascorbic acid can
      inhibit obesity and nonalcoholic fatty liver disease (NAFLD) in part through the
      actions of PPARalpha. DESIGN: After C57BL/6J mice received a low-fat diet (LFD,
      10% kcal fat), a high-fat diet (HFD, 45% kcal fat), or the same HFD supplemented
      with ascorbic acid (1% w/w) (HFD-AA) for 15 weeks, variables and determinants of
      visceral obesity and NAFLD were examined using metabolic measurements, histology,
      and gene expression. RESULTS: Compared to HFD-fed obese mice, administration of
      HFD-AA to obese mice reduced body weight gain, visceral adipose tissue mass, and
      visceral adipocyte size without affecting food consumption profiles.
      Concomitantly, circulating ascorbic acid concentrations were significantly higher
      in HFD-AA mice than in HFD mice. Ascorbic acid supplementation increased the mRNA
      levels of PPARalpha and its target enzymes involved in fatty acid beta-oxidation
      in visceral adipose tissues. Consistent with the effects of ascorbic acid on
      visceral obesity, ascorbic acid not only inhibited hepatic steatosis but also
      increased the mRNA levels of PPARalpha-dependent fatty acid beta-oxidation genes
      in livers. Similarly, hepatic inflammation, fibrosis, and apoptosis were also
      decreased during ascorbic acid-induced inhibition of visceral obesity. In
      addition, serum levels of alanine aminotransferase, aspartate aminotransferase,
      total cholesterol, and LDL cholesterol were lower in HFD-AA-fed mice than in
      those of HFD-fed mice. CONCLUSIONS: These results suggest that ascorbic acid
      seems to suppress HFD-induced visceral obesity and NAFLD in part through the
      activation of PPARalpha.

PMID- 30283078
TI  - Working toward precision medicine approaches to treat severe obesity in
      adolescents: report of an NIH workshop.
AB  - Adolescent severe obesity is a prevalent, chronic, and serious disease with few
      effective and safe treatment options. To address this issue, a National
      Institutes of Health-sponsored workshop entitled "Developing Precision Medicine
      Approaches to the Treatment of Severe Obesity in Adolescents," was convened,
      bringing together a multidisciplinary group of experts to review the current
      state of the science and identify (1) what is known regarding the epidemiology
      and biopsychosocial determinants of severe obesity in adolescents, (2) what is
      known regarding effectiveness of treatments for severe obesity in adolescents and
      predictors of response, and (3) gaps and opportunities for future research to
      develop more effective and targeted treatments for adolescents with severe
      obesity. Major topical areas discussed at the workshop included: appropriate BMI
      metrics, valid measures of phenotypes and predictors, mechanisms associated with
      the development of severe obesity, novel treatments informed by biologically and
      psychosocially plausible mechanisms, biopsychosocial phenotypes predicting
      treatment response, standardization of outcome measures and results reporting in
      research, and improving clinical care. Substantial gaps in knowledge were
      identified regarding the basic behavioral, psychosocial, and biological
      mechanisms driving the development of severe obesity and the influence of these
      factors on treatment response. Additional exploratory and observational studies
      are needed to better understand the heterogeneous etiology of severe obesity and
      explain the high degree of variability observed with interventions. Tailored
      treatment strategies that may be developed by achieving a better understanding of
      individual differences in genetic endowment, clinical, metabolic, psychological,
      and behavioral phenotypes, and response to environmental exposures need to be
      tested. It is anticipated that these recommendations for future research,
      including strategies to enhance methodological rigor, will advance precision
      medicine approaches to treat severe obesity in adolescents more effectively.

PMID- 30283079
TI  - Sugar-sweetened beverage intake and relative weight gain among South African
      adults living in resource-poor communities: longitudinal data from the STOP-SA
      study.
AB  - OBJECTIVES: This study examines the prospective association between sugar
      sweetened beverages (SSB) consumption and change in body weight over a 4-5-year
      period in a socio-economically disadvantaged South African population. METHODS:
      This is a longitudinal study involving 800 adults (212 men, 588 women); 247 from
      the original METS (Modelling the Epidemiological Transition Study) cohort (N =
      504) and 553 of the original 949 members of the PURE (Prospective Urban and Rural
      Epidemiology) Study. Both cohorts were drawn from low-income, socio-economically
      disadvantaged communities. Mean follow-up duration and age were 4.5 (SD 0.45) and
      50.0 (SD 11.8) years, respectively. Harmonised measurements included body mass
      index, self-reported moderate-to-vigorous physical activity, and intake of meat,
      snacks and 'take-aways', fruits and vegetables and SSB (in servings/week).
      Multivariate logistic regression models were developed to determine the extent to
      which SSB consumption predicted relative weight gain, after controlling for
      potential confounders and known predictors. RESULTS: Nearly a third (29%) of
      participants had a relative weight change >=5.0%; higher in the non-obese
      compared to the obese group (32% vs. 25%; p = 0.026). The average SSB consumption
      was 9.9 servings/week and was higher in the food insecure compared to the food
      secure group (11.5 vs. 9.0 servings/week; p = 0.006); but there were no
      differences between women and men (10.3 vs. 9.1 servings/week; p = 0.054). Mean
      SSB consumption was higher in the group who gained >=5% weight compared to those
      who did not (11.0 vs. 8.7; p = 0.004). After adjustment, SSB consumption of 10 or
      more servings/week was associated with a 50% greater odds of gaining at least 5%
      body weight (AOR: 1.50, 95% CI (1.05-2.18)). CONCLUSION: These results show that
      higher intake of SSB predicts weight gain in a sample of South Africans drawn
      from low-income settings. Comprehensive, population-wide interventions are needed
      to reduce SSB consumption in these settings.

PMID- 30283080
TI  - Fluorescent blood-brain barrier tracing shows intact leptin transport in obese
      mice.
AB  - BACKGROUND/OBJECTIVES: Individuals carrying loss-of-function gene mutations for
      the adipocyte hormone leptin are morbidly obese, but respond favorably to
      replacement therapy. Recombinant leptin is however largely ineffective for the
      vast majority of obese individuals due to leptin resistance. One theory
      underlying leptin resistance is impaired leptin transport across the blood-brain
      barrier (BBB). Here, we aim to gain new insights into the mechanisms of leptin
      BBB transport, and its role in leptin resistance. METHODS: We developed a novel
      tool for visualizing leptin transport using infrared fluorescently labeled
      leptin, combined with tissue clearing and light-sheet fluorescence microscopy. We
      corroborated these data using western blotting. RESULTS: Using 3D whole brain
      imaging, we display comparable leptin accumulation in circumventricular organs of
      lean and obese mice, predominantly in the choroid plexus (CP). Protein
      quantification revealed comparable leptin levels in microdissected mediobasal
      hypothalami (MBH) of lean and obese mice (p = 0.99). We further found increased
      leptin receptor expression in the CP (p = 0.025, p = 0.0002) and a trend toward
      elevated leptin protein levels in the MBH (p = 0.17, p = 0.078) of obese mice
      undergoing weight loss interventions by calorie restriction or exendin-4
      treatment. CONCLUSIONS: Overall, our findings suggest a crucial role for the CP
      in controlling the transport of leptin into the cerebrospinal fluid and from
      there to target areas such as the MBH, potentially mediated via the leptin
      receptor. Similar leptin levels in circumventricular organs and the MBH of lean
      and obese mice further suggest intact leptin BBB transport in leptin resistant
      mice.

PMID- 30283081
TI  - Mammalian nucleolar protein DCAF13 is essential for ovarian follicle maintenance
      and oocyte growth by mediating rRNA processing.
AB  - During mammalian oocyte growth, chromatin configuration transition from the
      nonsurrounded nucleolus (NSN) to surrounded nucleolus (SN) type plays a key role
      in the regulation of gene expression and acquisition of meiotic and developmental
      competence by the oocyte. Nonetheless, the mechanism underlying chromatin
      configuration maturation in oocytes is poorly understood. Here we show that
      nucleolar protein DCAF13 is an important component of the ribosomal RNA (rRNA)
      processing complex and is essential for oocyte NSN-SN transition in mice. A
      conditional knockout of Dcaf13 in oocytes led to the arrest of oocyte development
      in the NSN configuration, follicular atresia, premature ovarian failure, and
      female sterility. The DCAF13 deficiency resulted in pre-rRNA accumulation in
      oocytes, whereas the total mRNA level was not altered. Further exploration showed
      that DCAF13 participated in the 18S rRNA processing in growing oocytes. The lack
      of 18S rRNA because of DCAF13 deletion caused a ribosome assembly disorder and
      then reduced global protein synthesis. DCAF13 interacted with a protein of the
      core box C/D ribonucleoprotein, fibrillarin, i.e., a factor of early pre-rRNA
      processing. When fibrillarin was knocked down in the oocytes from primary
      follicles, follicle development was inhibited as well, indicating that an rRNA
      processing defect in the oocyte indeed stunts chromatin configuration transition
      and follicle development. Taken together, these results elucidated the in vivo
      function of novel nucleolar protein DCAF13 in maintaining mammalian oogenesis.

PMID- 30283082
TI  - Hypoxia-induced autophagy of stellate cells inhibits expression and secretion of
      lumican into microenvironment of pancreatic ductal adenocarcinoma.
AB  - Lumican is secreted by pancreatic stellate cells and inhibits cancer progression.
      Extracellular lumican inhibits cancer cell replication and restrains growth of
      early-stage pancreatic adenocarcinoma (PDAC) such that patients with tumors
      containing stromal lumican experience a three-fold longer survival after
      treatment. In the present study, patient tumor tissues, ex-vivo cultures of
      patient-derived xenografts (PDX), PDAC stellate and tumor cells were used to
      investigate whether hypoxia (1% O2) within the tumor microenvironment influences
      stromal lumican expression and secretion. We observed that hypoxia significantly
      reduced lumican expression and secretion from pancreatic stellate cells, but not
      cancer cells. Although hypoxia enhanced lactate dehydrogenase A (LDHA) expression
      and lactate secretion from all cells, neither hypoxia-induced nor exogenous
      lactate influenced lumican expression. Autophagy was induced by hypoxia in ex
      vivo cultures of PDX and pancreatic stellate cells, but not cancer cells cultured
      in 2D. Autophagic flux inhibitors, bafilomycin A1, chloroquine diphosphate salt,
      and ammonium chloride prevented hypoxia-mediated reduction in lumican expression
      in stellate cells. Furthermore, inhibition of AMP-regulated protein kinase (AMPK)
      phosphorylation or hypoxia-inducible factor (HIF)-1alpha expression within
      hypoxic stellate cells restored lumican expression levels. Hypoxia did not affect
      lumican mRNA expression, indicating that hypoxia-induced reduction of lumican
      occurs post-transcriptionally; in addition, AMPK inhibition prevented hypoxia
      reduced phosphorylation of the mTOR/p70S6K/4EBP signaling pathway, a key
      contributor to protein synthesis. Taken together, these findings demonstrate that
      hypoxia reduces stromal lumican in PDAC through autophagy-mediated degradation
      and reduction in protein synthesis within pancreatic cancer stellate cells.

PMID- 30283083
TI  - Synthesis and characterization of monodispersed water dispersible Fe3O4
      nanoparticles and in vitro studies on human breast carcinoma cell line under
      hyperthermia condition.
AB  - Monodispersed Fe3O4 magnetic nanoparticles (MNPs) having size of 7 nm have been
      prepared from iron oleate and made water dispersible by functionalization for
      biomedical applications. Three different reactions employing thioglycolic acid,
      aspartic acid and aminophosphonate were performed on oleic acid coated Fe3O4. In
      order to achieve a control on particle size, the pristine nanoparticles were
      heated in presence of ferric oleate which led to increase in size from 7 to 11
      nm. Reaction parameters such as rate of heating, reaction temperature and
      duration of heating have been studied. Shape of particles was found to change
      from spherical to cuboid. The cuboid shape in turn enhances magneto-crystalline
      anisotropy (Ku). Heating efficacy of these nanoparticles for hyperthermia was
      also evaluated for different shapes and sizes. We demonstrate heat generation
      from these MNPs for hyperthermia application under alternating current (AC)
      magnetic field and optimized heating efficiency by controlling morphology of
      particles. We have also studied intra-cellular uptake and localization of
      nanoparticles and cytotoxicity under AC magnetic field in human breast carcinoma
      cell line.

PMID- 30283084
TI  - Impact of an infectious diseases specialist-led antimicrobial stewardship
      programmes on antibiotic use and antimicrobial resistance in a large Korean
      hospital.
AB  - The aim of this study was to evaluate the impact of an infectious diseases
      specialist (IDS)-led antimicrobial stewardship programmes (ASPs) in a large
      Korean hospital. An interrupted time series analysis assessing the trends in
      antibiotic use and antimicrobial resistance rate of major pathogens between
      September 2015 and August 2017 was performed in an 859-bed university-affiliated
      hospital in Korea. The restrictive measure for designated antibiotics led by an
      IDS reduced carbapenems usage by -4.57 days of therapy (DOT)/1,000 patient-days
      per month in general wards (GWs) (95% confidence interval [CI], -6.69 to -2.46; P
      < 0.001), and by -41.50 DOT/1,000 patient-days per month in intensive care units
      (ICUs) (95% CI, -57.91 to -25.10; P < 0.001). Similarly, glycopeptides usage
      decreased by -2.61 DOT/1,000 patient-days per month in GWs (95% CI, -4.43 to 
      0.79; P = 0.007), and -27.41 DOT/1,000 patient-days per month in ICUs (95% CI, 
      47.03 to -7.79; P = 0.009). Use of 3rd generation cephalosporins, beta
      lactam/beta-lactamase inhibitors, and fluoroquinolones in GWs showed change
      comparable with that of carbapenems or glycopeptides use. Furthermore, trends of
      antimicrobial resistance rate of Staphylococcus aureus to gentamicin in GWs,
      Staphylococcus aureus to ciprofloxacin and oxacillin in ICUs, and Pseudomonas
      aeruginosa to imipenem in ICUs decreased in slope in the intervention period. The
      in-hospital mortality rate per 1,000 patient-days among ICU patients remained
      stable between the pre-intervention and intervention periods. In conclusion, an
      IDS-led ASPs could enact a meaningful reduction in antibiotic use, and a decrease
      in antibiotic resistance rate, without changing mortality rates in a large Korean
      hospital.

PMID- 30283085
TI  - Dianhydrogalactitol induces replication-dependent DNA damage in tumor cells
      preferentially resolved by homologous recombination.
AB  - 1,2:5,6-Dianhydrogalactitol (DAG) is a bifunctional DNA-targeting agent causing
      N7-guanine alkylation and inter-strand DNA crosslinks currently in clinical trial
      for treatment of glioblastoma. While preclinical studies and clinical trials have
      demonstrated antitumor activity of DAG in a variety of malignancies,
      understanding the molecular mechanisms underlying DAG-induced cytotoxicity is
      essential for proper clinical qualification. Using non-small cell lung cancer
      (NSCLC) as a model system, we show that DAG-induced cytotoxicity materializes
      when cells enter S phase with unrepaired N7-guanine DNA crosslinks. In S phase,
      DAG-mediated DNA crosslink lesions translated into replication-dependent DNA
      double-strand breaks (DSBs) that subsequently triggered irreversible cell cycle
      arrest and loss of viability. DAG-treated NSCLC cells attempt to repair the DSBs
      by homologous recombination (HR) and inhibition of the HR repair pathway
      sensitized NSCLC cells to DAG-induced DNA damage. Accordingly, our work describes
      a molecular mechanism behind N7-guanine crosslink-induced cytotoxicity in cancer
      cells and provides a rationale for using DAG analogs to treat HR-deficient
      tumors.

PMID- 30283086
TI  - CCAAT/enhancer-binding protein-beta functions as a negative regulator of Wnt/beta
      catenin signaling through activation of AXIN1 gene expression.
AB  - Axin1, a concentration-limiting component of the beta-catenin destruction
      complex, negatively regulates the Wnt/beta-catenin pathway. Axin1 concentration
      is reported to be regulated by proteasomal degradation; however, its
      transcriptional regulation has not yet been reported. Here, we demonstrated that
      CCAAT/enhancer-binding protein-beta (C/EBP-beta) activates axis inhibition
      protein 1 (AXIN1) gene expression, thereby attenuating Wnt/beta-catenin
      signaling. C/EBP-beta interacted with cis-regulatory element for C/EBP-beta in
      the 5'-upstream sequences of the AXIN1 gene and increased AXIN1 promoter
      activity. Functional analysis using Drosophila and zebrafish models established
      that C/EBP-beta negatively regulates the Wnt/beta-catenin pathway. Small-molecule
      based up-regulation of C/EBP-beta induces AXIN1 gene expression and down
      regulates the intracellular beta-catenin level, thereby inhibiting hepatoma cell
      growth. Thus, our findings provide a unique mechanistic insight into the
      regulation of Axin homeostasis and present a novel strategy for the development
      of anticancer therapeutics targeting Wnt/beta-catenin signaling.

PMID- 30283087
TI  - MR imaging of subaortic and retroesophageal anomalous courses of the left
      brachiocephalic vein in the fetus.
AB  - The purpose of this study was to report fetal cases of subaortic and
      retroesophageal anomalous courses of the left brachiocephalic vein (LBCV)
      evaluated by fetal cardiac magnetic resonance imaging (MRI). A retrospective
      review of 7282 fetal cardiac MRI from June 2006 to March 2017, nine cases of
      anomalous courses of the LBCV were correctly diagnosed by fetal cardiac MRI, one
      case of abnormal subaortic left brachiocephalic vein (ASLBV) missed by fetal MRI
      was identified postnatally during further imaging of the TOF. The diagnosis was
      confirmed postnatally by cardiac CT/MRI. An ASLBV was found in 8 cases, a
      retroesophageal LBCV was found in 2 additional cases with right aortic arch and
      aberrant left subclavian artery. 3 of 8 ASLBV cases were with a right aortic
      arch, 4 ASLBV cases had additional cardiovascular anomalies with one case
      isolated. 7 of 8 ASLBV and 2 retroesophageal LBCV were correctly diagnosed by
      fetal cardiac MRI; however fetal cardiac MRI missed 2 cases of associated
      pulmonary atresia (PA). Prenatal echocardiography (echo) correctly diagnosed five
      ASLBV and one retroesophageal LBCV as well as associated intracardiac anomalies.
      Fetal cardiac MRI can be a useful adjunct in the identification of subaortic and
      retroesophageal anomalous courses of the LBCV prenatally.

PMID- 30283088
TI  - Ten-year incidence of hypertension in a Swiss population-based sample Incidence
      of hypertension in Switzerland.
AB  - Few studies assessed incidence and determinants of hypertension. We assessed the
      incidence and determinants of hypertension in a cohort of healthy adults aged 35
      75 years living in Lausanne, Switzerland. Baseline data were collected from 2003
      to 2006. Follow-ups were conducted in 2009-2012 and 2014-2017. Incident
      hypertension, defined as a systolic BP >=140 mm Hg or a diastolic BP >=90 mm Hg
      or anti-hypertensive medication, was assessed at 1) second follow-up only; 2)
      first and/or second follow-up. After 10.9 years, incident hypertension was 26.8%
      (analysis 1, N = 3299) and 30.3% (analysis 2, N = 3728). After multivariate
      adjustment, the variables associated with increased hypertension incidence were
      male gender [incident-rate ratio (IRR) and (95% confidence interval)]: 1.20 (1.07
      1.35) and 1.24 (1.13-1.37) for analyses 1 and 2, respectively; increasing age (p
      for trend < 0.001) and body mass index (p for trend < 0.001) and history of
      cardiovascular disease (CVD). Being physically active was negatively associated
      with incident hypertension: 0.88 (0.78-0.98) and 0.92 (0.83-1.01) for analyses 1
      and 2, respectively. Except for male gender, these associations remained after
      adjusting for baseline BP levels, with incident rate ratios for physical activity
      of 0.86 (0.77-0.96) and 0.91 (0.83-0.99) for analyses 1 and 2, respectively. No
      association was found for education, alcohol consumption or smoking status. We
      conclude that over 10.9 years, between 1/4 and 1/3 of the Swiss population aged
      35-75 developed hypertension. Male gender, history of CVD, increasing age and
      higher BMI increase the risk of hypertension, while being physically active
      reduces the risk.

PMID- 30283090
TI  - Disparities in the impact of overweight on hypertension among Asians: a Japanese
      and Thai population-based study.
AB  - The divergence in cardiovascular disease risk among Asian countries may be
      related to differences in economics, lifestyles, and cultural backgrounds. We
      examined the differential association of overweight and hypertension between the
      high- and middle-income Asian countries, namely Japan and Thailand and extended
      to compare other cardiovascular risk factors between these two countries, using
      the data sets from the annual health examinations conducted in 127,152 Japanese
      (mean age, 41.5 +/- 11.1 years; mean body mass index [BMI], 22.4 +/- 3.4 kg/m2)
      and 4243 Thai (mean age, 47.9 +/- 10.7 years: mean BMI, 24.0 +/- 3.7 kg/m2) aged
      over 18 years with no history of hypertension treatment. Hypertension was
      diagnosed as office SBP >= 130 mmHg and/or office DBP >= 80 mmHg. Overweight was
      defined as BMI >= 25 kg/m2. The analysis using the direct standardization method
      showed a lower prevalence of hypertension in the Japanese than in the Thai
      population (31.8% vs. 57.3%, P < 0.001). The Japanese population had higher
      estimated glomerular filtration rate and lower cholesterol level and BMI than in
      the Thai population (all P < 0.001). The association between overweight and
      hypertension was observed in both populations regardless of age and sex (all P <
      0.05). In the analysis stratified by age and sex, the association between
      overweight and the presence of hypertension was more prominent in the Japanese
      population aged <50 years in both sexes compared with the Thai population (all P
      for interaction < 0.001). These results confirmed the differential impact of
      overweight on hypertension between the high- and middle-income countries even in
      the similar regions of Asia.

PMID- 30283089
TI  - A gender-specific association of the polymorphism Ile197Met in the kininogen 1
      gene with plasma irbesartan concentrations in Chinese patients with essential
      hypertension.
AB  - This study was conducted to explore interactions in the association of the
      kininogen (KNG1) Ile197Met polymorphism and gender with plasma concentrations of
      irbesartan in Chinese patients with essential hypertension. A total of 1100
      subjects with essential hypertension received a daily oral dose of 150 mg
      irbesartan for twenty-eight consecutive days. High-performance liquid
      chromatography-fluorescence (HPLC) was used to detect plasma irbesartan
      concentrations on day 28. The KNG1 Ile197Met gene polymorphism was determined
      using high-throughput TaqMan technology. The frequency distribution of KNG1
      Ile197Met genotype conformed to the Hardy-Weinberg equilibrium. After 28 days of
      treatment, patients with the GG genotype had significantly lower irbesartan
      concentrations (P = 0.033) compared to homozygous TT genotype carriers. After
      stratifying by gender, male G allele carriers had significantly lower irbesartan
      concentrations (GG, P = 0.015; TG, P = 0.015, respectively) relative to TT
      genotype after adjusting for age, region, body mass index (BMI), smoking, and
      alcohol consumption. However, there was no significant difference in female
      subjects. A further test for a multiplicative interaction between the KNG1
      Ile197Met polymorphism and gender in association with ln-plasma irbesartan
      concentrations in a multiple linear regression model was also significant (P for
      interaction = 0.033). This is the first study to suggest that gender may
      influence the association of the Ile197Met variant of KNG1 with ln-plasma
      irbesartan concentration. This finding may indicate that the interaction of
      gender and the KNG1 Ile197Met gene polymorphism can influence plasma trough
      irbesartan concentrations, which may contribute to a better development of
      personalized hypertensive treatment in Chinese patients.

PMID- 30283091
TI  - Afar triple junction triggered by plume-assisted bi-directional continental break
      up.
AB  - Divergent ridge-ridge-ridge (R-R-R) triple junctions are one of the most
      remarkable, yet largely enigmatic, features of plate tectonics. The juncture of
      the Arabian, Nubian, and Somalian plates is a type-example of the early
      development stage of a triple junction where three active rifts meet at a 'triple
      point' in Central Afar. This structure may result from the impingement of the
      Afar plume into a non-uniformly stressed continental lithosphere, but this
      process has never been reproduced by self-consistent plume-lithosphere
      interaction experiments. Here we use 3D thermo-mechanical numerical models to
      examine the initiation of plume-induced rift systems under variable far-field
      stress conditions. Whereas simple linear rift structures are preferred under uni
      directional extension, we find that more complex patterns form in response to bi
      directional extension, combining one or several R-R-R triple junctions. These
      triple junctions optimize the geometry of continental break-up by minimizing the
      amount of dissipative mechanical work required to accommodate multi-directional
      extension. Our models suggest that Afar-like triple junctions are an end-member
      mode of plume-induced bi-directional rifting that combines asymmetrical northward
      pull and symmetrical EW extension at similar rates.

PMID- 30283092
TI  - Two coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression
      in the mouse suprachiasmatic nucleus.
AB  - Circadian rhythms in clock genes, Bmal1 and Per2 expression were monitored
      simultaneously in the cultured slice of mouse suprachiasmatic nucleus (SCN) by
      dual bioluminescent reporters. In the neonatal SCN, the phase-relation between
      the Bmal1 and Per2 rhythms were significantly changed during culture. Medium
      exchange produced phase-dependent phase shifts (PRCm) in the Bmal1 rhythms, but
      not in the Per2 rhythms. As a result, the two circadian rhythms were temporally
      dissociated after medium exchange. In the adult SCN, the phase-relation between
      the two rhythms was kept constant during culture at least up to 20 cycles. The
      amplitude of PRCm in the adult SCN was significantly attenuated in the Bmal1
      rhythm, whereas a PRCm was developed in the Per2 rhythm. The circadian period was
      not systematically affected by medium exchange in either of rhythms, regardless
      of whether it was in the neonatal or the adult SCN. Tetrodotoxin, a sodium
      channel blocker, enhanced the phase-response in both rhythms but abolished the
      phase-dependency. In addition, tetrodotoxin lengthened the circadian period
      independent of the phase of administration. Thus, the Bmal1 and Per2 rhythms in
      the SCN are dissociable and likely regulated by distinct circadian oscillators.
      Bmal1 is the component of a Bmal1/REV-ERBa/ROR loop and Per2 a
      Per/Cry/BMAL1/CLOCK loop. Both loops could be molecular mechanisms of the two
      circadian oscillators that are coupled through the protein product of Bmal1. The
      coupling strength between the two oscillations depends on developmental stages.

PMID- 30283094
TI  - Growth hormone excess in neurofibromatosis 1.

PMID- 30283093
TI  - Evaluation of Hypoglycaemia with Non-Invasive Sensors in People with Type 1
      Diabetes and Impaired Awareness of Hypoglycaemia.
AB  - People with type 1 diabetes and impaired awareness of hypoglycaemia (IAH) are
      prone to severe hypoglycaemia. Previous attempts to develop non-invasive
      hypoglycaemia alarm systems have shown promising results, but it is not known if
      such alarms can detect severe hypoglycaemia in people with IAH. We aimed to
      explore whether a combination of non-invasive sensors could reliably evaluate
      hypoglycaemia (plasma glucose (PG) minimum 2.5 mmol/L) in people with IAH. Twenty
      participants with type 1 diabetes and IAH underwent randomly ordered, single
      blinded hyperinsulinemic euglycaemic and hyperinsulinemic hypoglycaemic clamps.
      Sweating, skin temperature, ECG, counterregulatory hormones and symptoms of
      hypoglycaemia were assessed. Overall, we were not able to detect clamp-induced
      hypoglycaemia with sufficient sensitivity and specificity for further clinical
      use. As a post-hoc analysis, we stratified participants according to their
      ability to identify hypoglycaemic symptoms during hypoglycaemic clamps. Five out
      of 20 participants could identify such symptoms. These participants had a
      significantly higher adrenaline response to hypoglycaemia (p < 0.001) and were
      reliably identified by sensors. Based on our observations, a non-invasive alarm
      system based on measurement of sweating responses and ECG changes during
      hypoglycaemia might provide an alert at a plasma glucose concentration around 2.5
      mmol/L if an adequate sympatho-adrenal reaction is elicited.

PMID- 30283096
TI  - Response to Esplin et al.

PMID- 30283095
TI  - Response to Hannah-Shmouni and Stratakis.

PMID- 30283097
TI  - Gut Colonization with Methanogenic Archaea Lowers Plasma Trimethylamine N-oxide
      Concentrations in Apolipoprotein e-/- Mice.
AB  - A mechanistic link between trimethylamine N-oxide (TMAO) and atherogenesis has
      been reported. TMAO is generated enzymatically in the liver by the oxidation of
      trimethylamine (TMA), which is produced from dietary choline, carnitine and
      betaine by gut bacteria. It is known that certain members of methanogenic archaea
      (MA) could use methylated amines such as trimethylamine as growth substrates in
      culture. Therefore, we investigated the efficacy of gut colonization with MA on
      lowering plasma TMAO concentrations. Initially, we screened for the colonization
      potential and TMAO lowering efficacy of five MA species in C57BL/6 mice fed with
      high choline/TMA supplemented diet, and found out that all five species could
      colonize and lover plasma TMAO levels, although with different efficacies. The
      top performing MA, Methanobrevibacter smithii, Methanosarcina mazei, and
      Methanomicrococcus blatticola, were transplanted into Apoe-/- mice fed with high
      choline/TMA supplemented diet. Similar to C57BL/6 mice, following initial
      provision of the MA, there was progressive attrition of MA within fecal microbial
      communities post-transplantation during the initial 3 weeks of the study. In
      general, plasma TMAO concentrations decreased significantly in proportion to the
      level of MA colonization. In a subsequent experiment, use of antibiotics and
      repeated transplantation of Apoe-/- mice with M. smithii, led to high engraftment
      levels during the 9 weeks of the study, resulting in a sustained and
      significantly lower average plasma TMAO concentrations (18.2 +/- 19.6 MUM)
      compared to that in mock-transplanted control mice (120.8 +/- 13.0 MUM, p <
      0.001). Compared to control Apoe-/- mice, M. smithii-colonized mice also had a
      44% decrease in aortic plaque area (8,570 MUm [95% CI 19587-151821] vs. 15,369
      MUm [95% CI [70058-237321], p = 0.34), and 52% reduction in the fat content in
      the atherosclerotic plaques (14,283 MUm [95% CI 4,957-23,608] vs. 29,870 MUm [95%
      CI 18,074-41,666], p = 0.10), although these differences did not reach
      significance. Gut colonization with M. smithii leads to a significant reduction
      in plasma TMAO levels, with a tendency for attenuation of atherosclerosis burden
      in Apoe-/- mice. The anti-atherogenic potential of MA should be further tested in
      adequately powered experiments.

PMID- 30283098
TI  - NF-kappaB-related decrease of glioma angiogenic potential by graphite
      nanoparticles and graphene oxide nanoplatelets.
AB  - Gliomas develop an expanded vessel network and a microenvironment characterized
      by an altered redox environment, which produces high levels of reactive oxygen
      species (ROS) and reactive nitrogen species (RNS) that fuel its growth and
      malignancy. ROS and RNS can influence tumor cell malignancy via the redox
      regulated transcription factor NF-kappaB, whose activation is further regulated
      by the mutation status of p53. The objective of this study was to assess the
      influence of graphite nanoparticles (NG) and graphene oxide nanoplatelets (nGO)
      on the angiogenic potential of glioma cell lines with different p53 statuses.
      Nanoparticle treatment of glioma cells decreased the angiogenesis of human
      umbilical vein endothelial cells (HUVEC) cocultured with U87 (p53 wild type) and
      was not effective for U118 (p53 mutant) cells. Nanoparticle activity was related
      to the decreased level of intracellular ROS and RNS, which downregulated NF
      kappaB signaling depending on the p53 status of the cell line. Activation of NF
      kappaB signaling affected downstream protein levels of interleukin 6, interleukin
      8, growth-regulated oncogene alpha, and monocyte chemotactic protein 1. These
      results indicate that the activity of NG and nGO can be regulated by the mutation
      status of glioma cells and therefore give new insights into the use of
      nanoparticles in personalized biomedical applications regarding glioma
      angiogenesis and its microenvironment.

PMID- 30283099
TI  - Connectivity of larval stages of sedentary marine communities between hard
      substrates and offshore structures in the North Sea.
AB  - Man-made structures including rigs, pipelines, cables, renewable energy devices,
      and ship wrecks, offer hard substrate in the largely soft-sediment environment of
      the North Sea. These structures become colonised by sedentary organisms and non
      migratory reef fish, and form local ecosystems that attract larger predators
      including seals, birds, and fish. It is possible that these structures form a
      system of interconnected reef environments through the planktonic dispersal of
      the pelagic stages of organisms by ocean currents. Changes to the overall
      arrangement of hard substrate areas through removal or addition of individual man
      made structures will affect the interconnectivity and could impact on the
      ecosystem. Here, we assessed the connectivity of sectors with oil and gas
      structures, wind farms, wrecks, and natural hard substrate, using a model that
      simulates the drift of planktonic stages of seven organisms with sedentary adult
      stages associated with hard substrate, applied to the period 2001-2010.
      Connectivity was assessed using a classification system designed to address the
      function of sectors in the network. Results showed a relatively stable overall
      spatial distribution of sector function but with distinct variations between
      species and years. The results are discussed in the context of decommissioning of
      oil and gas infrastructure in the North Sea.

PMID- 30283100
TI  - Complex rice systems to improve rice yield and yield stability in the face of
      variable weather conditions.
AB  - Extreme weather events and pest outbreaks decrease rice yields and increase their
      variability, presenting challenges for the agricultural agenda to increase rice
      productivity and yield stability in Asia. The integration of azolla, fish and
      ducks has been shown to create robust systems that maintain high yields under
      heavy rainfall, but no clear evidence exists that rice yields in these systems
      are stable across locations and throughout time under divergent weather
      conditions. We show that the introduction of additional elements into the rice
      cropping system enhanced the adaptive capacity to extreme weather events across
      four locations and three cropping cycles. The complex system showed both static
      and dynamic stability, and had the highest reliability index, thereby
      outperforming the conventional and organic monoculture systems. The complex rice
      system design provides a promising example for resilience towards the impacts of
      climate change on rice production and for safeguarding food security in Asia and
      beyond.

PMID- 30283101
TI  - Recommendation for an internationally agreed minimum data set for teleneurology.

PMID- 30283102
TI  - Ferroelectric polymers exhibiting behaviour reminiscent of a morphotropic phase
      boundary.
AB  - Piezoelectricity-the direct interconversion between mechanical and electrical
      energies-is usually remarkably enhanced at the morphotropic phase boundary of
      ferroelectric materials1-4, which marks a transition region in the phase diagram
      of piezoelectric materials and bridges two competing phases with distinct
      symmetries1,5. Such enhancement has enabled the recent development of various
      lead and lead-free piezoelectric perovskites with outstanding piezoelectric
      properties for use in actuators, transducers, sensors and energy-harvesting
      applications5-8. However, the morphotropic phase boundary has never been observed
      in organic materials, and the absence of effective approaches to improving the
      intrinsic piezoelectric responses of polymers9,10 considerably hampers their
      application to flexible, wearable and biocompatible devices. Here we report
      stereochemically induced behaviour in ferroelectric poly(vinylidene fluoride-co
      trifluoroethylene) (P(VDF-TrFE)) copolymers, which is similar to that observed at
      morphotropic phase boundaries in perovskites. We reveal that compositionally
      tailored tacticity (the stereochemical arrangement of chiral centres related to
      the TrFE monomers11,12) can lead to intramolecular order-to-disorder evolution in
      the crystalline phase and thus to an intermediate transition region that is
      reminiscent of the morphotropic phase boundary, where competing ferroelectric and
      relaxor properties appear simultaneously. Our first-principles calculations
      confirm the crucial role of chain tacticity in driving the formation of this
      transition region via structural competition between the trans-planar and 3/1
      helical phases. We show that the P(VDF-TrFE) copolymer with the morphotropic
      composition exhibits a longitudinal piezoelectric coefficient of -63.5
      picocoulombs per newton, outperforming state-of-the-art piezoelectric polymers10.
      Given the flexibility in the molecular design and synthesis of organic
      ferroelectric materials, this work opens up the way for the development of
      scalable, high-performance piezoelectric polymers.

PMID- 30283103
TI  - Asymmetric alpha-arylation of amino acids.
AB  - Quaternary amino acids, in which the alpha-carbon that bears the amino and
      carboxyl groups also carries two carbon substituents, have an important role as
      modifiers of peptide conformation and bioactivity and as precursors of
      medicinally important compounds1,2. In contrast to enantioselective alkylation at
      this alpha-carbon, for which there are several methods3-8, general
      enantioselective introduction of an aryl substituent at the alpha-carbon is
      synthetically challenging9. Nonetheless, the resultant alpha-aryl amino acids and
      their derivatives are valuable precursors to bioactive molecules10,11. Here we
      describe the synthesis of quaternary alpha-aryl amino acids from enantiopure
      amino acid precursors by alpha-arylation without loss of stereochemical
      integrity. Our approach relies on the temporary formation of a second stereogenic
      centre in an N'-arylurea adduct12 of an imidazolidinone derivative6 of the
      precursor amino acid, and uses readily available enantiopure amino acids both as
      a precursor and as a source of asymmetry. It avoids the use of valuable
      transition metals, and enables arylation with electron-rich, electron-poor and
      heterocyclic substituents. Either enantiomer of the product can be formed from a
      single amino acid precursor. The method is practical and scalable, and provides
      the opportunity to produce alpha-arylated quaternary amino acids in multi-gram
      quantities.

PMID- 30283104
TI  - A new era in the search for dark matter.
AB  - There is a growing sense of 'crisis' in the dark-matter particle community, which
      arises from the absence of evidence for the most popular candidates for dark
      matter particles-such as weakly interacting massive particles, axions and sterile
      neutrinos-despite the enormous effort that has gone into searching for these
      particles. Here we discuss what we have learned about the nature of dark matter
      from past experiments and the implications for planned dark-matter searches in
      the next decade. We argue that diversifying the experimental effort and
      incorporating astronomical surveys and gravitational-wave observations is our
      best hope of making progress on the dark-matter problem.

PMID- 30283105
TI  - Widespread seasonal compensation effects of spring warming on northern plant
      productivity.
AB  - Climate change is shifting the phenological cycles of plants1, thereby altering
      the functioning of ecosystems, which in turn induces feedbacks to the climate
      system2. In northern (north of 30 degrees  N) ecosystems, warmer springs lead
      generally to an earlier onset of the growing season3,4 and increased ecosystem
      productivity early in the season5. In situ6 and regional7-9 studies also provide
      evidence for lagged effects of spring warmth on plant productivity during the
      subsequent summer and autumn. However, our current understanding of these lagged
      effects, including their direction (beneficial or adverse) and geographic
      distribution, is still very limited. Here we analyse satellite, field-based and
      modelled data for the period 1982-2011 and show that there are widespread and
      contrasting lagged productivity responses to spring warmth across northern
      ecosystems. On the basis of the observational data, we find that roughly 15 per
      cent of the total study area of about 41 million square kilometres exhibits
      adverse lagged effects and that roughly 5 per cent of the total study area
      exhibits beneficial lagged effects. By contrast, current-generation terrestrial
      carbon-cycle models predict much lower areal fractions of adverse lagged effects
      (ranging from 1 to 14 per cent) and much higher areal fractions of beneficial
      lagged effects (ranging from 9 to 54 per cent). We find that elevation and
      seasonal precipitation patterns largely dictate the geographic pattern and
      direction of the lagged effects. Inadequate consideration in current models of
      the effects of the seasonal build-up of water stress on seasonal vegetation
      growth may therefore be able to explain the differences that we found between our
      observation-constrained estimates and the model-constrained estimates of lagged
      effects associated with spring warming. Overall, our results suggest that for
      many northern ecosystems the benefits of warmer springs on growing-season
      ecosystem productivity are effectively compensated for by the accumulation of
      seasonal water deficits, despite the fact that northern ecosystems are thought to
      be largely temperature- and radiation-limited10.

PMID- 30283107
TI  - Don't dismiss pet genomics - tests help breeders.

PMID- 30283108
TI  - United Kingdom should learn from global body for biodiversity.

PMID- 30283109
TI  - China's electricity switch won't be swift or painless.

PMID- 30283110
TI  - New jargon seeping slowly into biodiversity world.

PMID- 30283111
TI  - Ferroelectric polymers morph into action.

PMID- 30283106
TI  - Very-high-energy particle acceleration powered by the jets of the microquasar SS
      433.
AB  - SS 433 is a binary system containing a supergiant star that is overflowing its
      Roche lobe with matter accreting onto a compact object (either a black hole or
      neutron star)1-3. Two jets of ionized matter with a bulk velocity of
      approximately 0.26c (where c is the speed of light in vacuum) extend from the
      binary, perpendicular to the line of sight, and terminate inside W50, a supernova
      remnant that is being distorted by the jets2,4-8. SS 433 differs from other
      microquasars (small-scale versions of quasars that are present within our own
      Galaxy) in that the accretion is believed to be super-Eddington9-11, and the
      luminosity of the system is about 1040 ergs per second2,9,12,13. The lobes of W50
      in which the jets terminate, about 40 parsecs from the central source, are
      expected to accelerate charged particles, and indeed radio and X-ray emission
      consistent with electron synchrotron emission in a magnetic field have been
      observed14-16. At higher energies (greater than 100 gigaelectronvolts), the
      particle fluxes of gamma-rays from X-ray hotspots around SS 433 have been
      reported as flux upper limits6,17-20. In this energy regime, it has been unclear
      whether the emission is dominated by electrons that are interacting with photons
      from the cosmic microwave background through inverse-Compton scattering or by
      protons that are interacting with the ambient gas. Here we report
      teraelectronvolt gamma-ray observations of the SS 433/W50 system that spatially
      resolve the lobes. The teraelectronvolt emission is localized to structures in
      the lobes, far from the centre of the system where the jets are formed. We have
      measured photon energies of at least 25 teraelectronvolts, and these are
      certainly not Doppler-boosted, because of the viewing geometry. We conclude that
      the emission-from radio to teraelectronvolt energies-is consistent with a single
      population of electrons with energies extending to at least hundreds of
      teraelectronvolts in a magnetic field of about 16 microgauss.

PMID- 30283112
TI  - Cerise sky memories.

PMID- 30283113
TI  - US Supreme Court should prevent execution of murderer who no longer remembers his
      crime.

PMID- 30283115
TI  - Beating the odds to secure a permanent contract.

PMID- 30283114
TI  - CERN's physics uproar, quantum-satellite plans and Yellowstone grizzly
      protections.

PMID- 30283116
TI  - An ode to female space trainees, the creeping cost of climate change, and the
      fabric of history: Books in brief.

PMID- 30283117
TI  - Co-production from proposal to paper.

PMID- 30283118
TI  - Science shared.

PMID- 30283119
TI  - The best research is produced when researchers and communities work together.

PMID- 30283120
TI  - How three research groups are tearing down the ivory tower.

PMID- 30283122
TI  - Simulated labs are booming.

PMID- 30283121
TI  - Craft metrics to value co-production.

PMID- 30283123
TI  - Drawn to science.

PMID- 30283125
TI  - Boosting the number of students from underrepresented groups in physics.

PMID- 30283124
TI  - Science and technology education.

PMID- 30283126
TI  - Better teachers are needed to improve science education.

PMID- 30283127
TI  - Making children safer online.

PMID- 30283128
TI  - Expanding the reach of science.

PMID- 30283129
TI  - Thermal efficiency of a thermocell made of Prussian blue analogues.
AB  - Recently, it was reported that a thermocell can convert temperature into electric
      energy by using the difference in the thermal coefficient (alpha = dV/dT) of the
      redox potential (V) between the cathode and anode materials. Among battery
      materials, Prussian blue analogues (PBAs) are promising materials for thermocell,
      because alpha changes from approximately -0.3 mV/K in NaxMn[Fe(CN)6]0.83 3.5 H2O
      (NMF83) to approximately 1.3 mV/K in NaxCo[Fe(CN)6]0.92,9H2O (NCF90). In this
      work, we systematically investigated the thermal efficiency (eta) of the
      NMF83/NCF90 thermocell relative to the difference (DeltaT) between low (TL = 282
      K) and high (TH = 292-338 K) temperatures. We found that the thermal efficiency
      (eta) increased proportionally with DeltaT. The linear increase in eta is
      ascribed to the linear increase in the cell voltage (Vcell) and the charge
      (QNCF90) extracted from NCF90. Moreover, eta reached 3.19% at DeltaT = 56 K,
      which corresponds to 19% of the Carnot efficiency (etacarnot = 17.0%). We further
      confirmed that the magnitude of QNCF90 is quantitatively reproduced by the slopes
      of the discharge curves of NMF83 and NCF90.

PMID- 30283130
TI  - Caloric restriction promotes functional changes involving short-chain fatty acid
      biosynthesis in the rat gut microbiota.
AB  - Caloric restriction (CR) is known to promote health and longevity, likely via
      modification of the gut microbiota (GM). However, functional and metabolic
      changes induced in the GM during CR are still unidentified. Here, we investigated
      the short- and long-term effects of CR on the rat GM using a metaproteogenomic
      approach. We show that a switch from ad libitum (AL) low fat diet to CR in young
      rats is able to induce rapid and deep changes in their GM metaproteomic profile,
      related to a reduction of the Firmicutes/Bacteroidetes ratio and an expansion of
      lactobacilli. Specifically, we observed a significant change in the expression of
      the microbial enzymes responsible for short-chain fatty acid biosynthesis, with
      CR boosting propionogenesis and limiting butyrogenesis and acetogenesis.
      Furthermore, these CR-induced effects were maintained up to adulthood and started
      to be reversed after a short-term diet change. We also found that CR alters the
      abundance of an array of host proteins released in stool, mainly related to
      epithelial barrier integrity and inflammation. Hence, our results provide
      thorough information about CR-induced modifications to GM and host functional
      activity, and might constitute the basis for novel GM-based approaches aimed at
      monitoring the effectiveness of dietary interventions.

PMID- 30283132
TI  - Genomes of Asgard archaea encode profilins that regulate actin.
AB  - The origin of the eukaryotic cell is unresolved1,2. Metagenomics sequencing has
      recently identified several potential eukaryotic gene homologues in Asgard
      archaea3,4, consistent with the hypothesis that the eukaryotic cell evolved from
      within the Archaea domain. However, many of these eukaryotic-like sequences are
      highly divergent and the organisms have yet to be imaged or cultivated, which
      brings into question the extent to which these archaeal proteins represent
      functional equivalents of their eukaryotic counterparts. Here we show that Asgard
      archaea encode functional profilins and thereby establish that this archaeal
      superphylum has a regulated actin cytoskeleton, one of the hallmarks of the
      eukaryotic cell5. Loki profilin-1, Loki profilin-2 and Odin profilin adopt the
      typical profilin fold and are able to interact with rabbit actin-an interaction
      that involves proteins from species that diverged more than 1.2 billion years
      ago6. Biochemical experiments reveal that mammalian actin polymerizes in the
      presence of Asgard profilins; however, Loki, Odin and Heimdall profilins impede
      pointed-end elongation. These archaeal profilins also retard the spontaneous
      nucleation of actin filaments, an effect that is reduced in the presence of
      phospholipids. Asgard profilins do not interact with polyproline motifs and the
      profilin-polyproline interaction therefore probably evolved later in the Eukarya
      lineage. These results suggest that Asgard archaea possess a primordial, polar,
      profilin-regulated actin system, which may be localized to membranes owing to the
      sensitivity of Asgard profilins to phospholipids. Because Asgard archaea are also
      predicted to encode potential eukaryotic-like genes involved in membrane
      trafficking and endocytosis3,4, imaging is now necessary to elucidate whether
      these organisms are capable of generating eukaryotic-like membrane dynamics that
      are regulated by actin, such as are observed in eukaryotic cell movement,
      podosomes and endocytosis.

PMID- 30283133
TI  - Crystal structure of a membrane-bound O-acyltransferase.
AB  - Membrane-bound O-acyltransferases (MBOATs) are a superfamily of integral
      transmembrane enzymes that are found in all kingdoms of life1. In bacteria,
      MBOATs modify protective cell-surface polymers. In vertebrates, some MBOAT
      enzymes-such as acyl-coenzyme A:cholesterol acyltransferase and diacylglycerol
      acyltransferase 1-are responsible for lipid biosynthesis or phospholipid
      remodelling2,3. Other MBOATs, including porcupine, hedgehog acyltransferase and
      ghrelin acyltransferase, catalyse essential lipid modifications of secreted
      proteins such as Wnt, hedgehog and ghrelin, respectively4-10. Although many MBOAT
      proteins are important drug targets, little is known about their molecular
      architecture and functional mechanisms. Here we present crystal structures of
      DltB, an MBOAT responsible for the D-alanylation of cell-wall teichoic acid in
      Gram-positive bacteria11-16, both alone and in complex with the D-alanyl donor
      protein DltC. DltB contains a ring of 11 peripheral transmembrane helices, which
      shield a highly conserved extracellular structural funnel extending into the
      middle of the lipid bilayer. The conserved catalytic histidine residue is located
      at the bottom of this funnel and is connected to the intracellular DltC through a
      narrow tunnel. Mutation of either the catalytic histidine or the DltC-binding
      site of DltB abolishes the D-alanylation of lipoteichoic acid and sensitizes the
      Gram-positive bacterium Bacillus subtilis to cell-wall stress, which suggests
      cross-membrane catalysis involving the tunnel. Structure-guided sequence
      comparison among DltB and vertebrate MBOATs reveals a conserved structural core
      and suggests that MBOATs from different organisms have similar catalytic
      mechanisms. Our structures provide a template for understanding structure
      function relationships in MBOATs and for developing therapeutic MBOAT inhibitors.

PMID- 30283135
TI  - Transcriptional recording by CRISPR spacer acquisition from RNA.
AB  - The ability to record transcriptional events within a cell over time would help
      to elucidate how molecular events give rise to complex cellular behaviours and
      states. However, current molecular recording technologies capture only a small
      set of defined stimuli. Here we use CRISPR spacer acquisition to capture and
      convert intracellular RNAs into DNA, enabling DNA-based storage of
      transcriptional information. In Escherichia coli, we show that defined stimuli,
      such as an RNA virus or arbitrary sequences, as well as complex stimuli, such as
      oxidative stress, result in quantifiable transcriptional records that are stored
      within a population of cells. We demonstrate that the transcriptional records
      enable us to classify and describe complex cellular behaviours and to identify
      the precise genes that orchestrate differential cellular responses. In the
      future, CRISPR spacer acquisition-mediated recording of RNA followed by deep
      sequencing (Record-seq) could be used to reconstruct transcriptional histories
      that describe complex cell behaviours or pathological states.

PMID- 30283134
TI  - Multi-axial self-organization properties of mouse embryonic stem cells into
      gastruloids.
AB  - The emergence of multiple axes is an essential element in the establishment of
      the mammalian body plan. This process takes place shortly after implantation of
      the embryo within the uterus and relies on the activity of gene regulatory
      networks that coordinate transcription in space and time. Whereas genetic
      approaches have revealed important aspects of these processes1, a mechanistic
      understanding is hampered by the poor experimental accessibility of early post
      implantation stages. Here we show that small aggregates of mouse embryonic stem
      cells (ESCs), when stimulated to undergo gastrulation-like events and elongation
      in vitro, can organize a post-occipital pattern of neural, mesodermal and
      endodermal derivatives that mimic embryonic spatial and temporal gene expression.
      The establishment of the three major body axes in these 'gastruloids'2,3 suggests
      that the mechanisms involved are interdependent. Specifically, gastruloids
      display the hallmarks of axial gene regulatory systems as exemplified by the
      implementation of collinear Hox transcriptional patterns along an extending
      antero-posterior axis. These results reveal an unanticipated self-organizing
      capacity of aggregated ESCs and suggest that gastruloids could be used as a
      complementary system to study early developmental events in the mammalian embryo.

PMID- 30283136
TI  - OTX2 restricts entry to the mouse germline.
AB  - The successful segregation of germ cells from somatic lineages is vital for
      sexual reproduction and species survival. In the mouse, primordial germ cells
      (PGCs), precursors of all germ cells, are induced from the post-implantation
      epiblast1. Induction requires BMP4 signalling to prospective PGCs2 and the
      intrinsic action of PGC transcription factors3-6. However, the molecular
      mechanisms that connect BMP4 to induction of the PGC transcription factors that
      are responsible for segregating PGCs from somatic lineages are unknown. Here we
      show that the transcription factor OTX2 is a key regulator of these processes.
      Downregulation of Otx2 precedes the initiation of the PGC programme both in vitro
      and in vivo. Deletion of Otx2 in vitro markedly increases the efficiency of PGC
      like cell differentiation and prolongs the period of PGC competence. In the
      absence of Otx2 activity, differentiation of PGC-like cells becomes independent
      of the otherwise essential cytokine signals, with germline entry initiating even
      in the absence of the PGC transcription factor BLIMP1. Deletion of Otx2 in vivo
      increases PGC numbers. These data demonstrate that OTX2 functions repressively
      upstream of PGC transcription factors, acting as a roadblock to limit entry of
      epiblast cells to the germline to a small window in space and time, thereby
      ensuring correct numerical segregation of germline cells from the soma.

PMID- 30283131
TI  - Pathogenic variants in glutamyl-tRNAGln amidotransferase subunits cause a lethal
      mitochondrial cardiomyopathy disorder.
AB  - Mitochondrial protein synthesis requires charging mt-tRNAs with their cognate
      amino acids by mitochondrial aminoacyl-tRNA synthetases, with the exception of
      glutaminyl mt-tRNA (mt-tRNAGln). mt-tRNAGln is indirectly charged by a
      transamidation reaction involving the GatCAB aminoacyl-tRNA amidotransferase
      complex. Defects involving the mitochondrial protein synthesis machinery cause a
      broad spectrum of disorders, with often fatal outcome. Here, we describe nine
      patients from five families with genetic defects in a GatCAB complex subunit,
      including QRSL1, GATB, and GATC, each showing a lethal metabolic cardiomyopathy
      syndrome. Functional studies reveal combined respiratory chain enzyme
      deficiencies and mitochondrial dysfunction. Aminoacylation of mt-tRNAGln and
      mitochondrial protein translation are deficient in patients' fibroblasts cultured
      in the absence of glutamine but restore in high glutamine. Lentiviral rescue
      experiments and modeling in S. cerevisiae homologs confirm pathogenicity. Our
      study completes a decade of investigations on mitochondrial aminoacylation
      disorders, starting with DARS2 and ending with the GatCAB complex.

PMID- 30283137
TI  - Effects of climate warming on photosynthesis in boreal tree species depend on
      soil moisture.
AB  - Climate warming will influence photosynthesis via thermal effects and by altering
      soil moisture1-11. Both effects may be important for the vast areas of global
      forests that fluctuate between periods when cool temperatures limit
      photosynthesis and periods when soil moisture may be limiting to carbon gain4-6,9
      11. Here we show that the effects of climate warming flip from positive to
      negative as southern boreal forests transition from rainy to modestly dry periods
      during the growing season. In a three-year open-air warming experiment with
      juveniles of 11 temperate and boreal tree species, an increase of 3.4  degrees C
      in temperature increased light-saturated net photosynthesis and leaf diffusive
      conductance on average on the one-third of days with the wettest soils. In all 11
      species, leaf diffusive conductance and, as a result, light-saturated net
      photosynthesis decreased during dry spells, and did so more sharply in warmed
      plants than in plants at ambient temperatures. Consequently, across the 11
      species, warming reduced light-saturated net photosynthesis on the two-thirds of
      days with driest soils. Thus, low soil moisture may reduce, or even reverse, the
      potential benefits of climate warming on photosynthesis in mesic, seasonally cold
      environments, both during drought and in regularly occurring, modestly dry
      periods during the growing season.

PMID- 30283138
TI  - Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys.
AB  - The latent viral reservoir is the critical barrier for the development of a cure
      for HIV-1 infection. Previous studies have shown direct antiviral activity of
      potent HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) administered
      when antiretroviral therapy (ART) was discontinued, but it remains unclear
      whether bNAbs can target the viral reservoir during ART. Here we show that
      administration of the V3 glycan-dependent bNAb PGT121 together with the Toll-like
      receptor 7 (TLR7) agonist vesatolimod (GS-9620) during ART delayed viral rebound
      following discontinuation of ART in simian-human immunodeficiency virus (SHIV)
      SF162P3-infected rhesus monkeys in which ART was initiated during early acute
      infection. Moreover, in the subset of monkeys that were treated with both PGT121
      and GS-9620 and that did not show viral rebound after discontinuation of ART,
      adoptive transfer studies and CD8-depletion studies also did not reveal virus.
      These data demonstrate the potential of bNAb administration together with innate
      immune stimulation as a possible strategy for targeting the viral reservoir.

PMID- 30283139
TI  - Solution-processable 2D semiconductors for high-performance large-area
      electronics.
AB  - Two-dimensional (2D) materials, consisting of atomically thin crystal layers
      bound by the van der Waals force, have attracted much interest because of their
      potential in diverse technologies, including electronics, optoelectronics and
      catalysis1-10. In particular, solution-processable 2D semiconductor (such as
      MoS2) nanosheets are attractive building blocks for large-area thin-film
      electronics. In contrast to conventional zero- and one-dimensional nanostructures
      (quantum dots and nanowires, respectively), which are typically plagued by
      surface dangling bonds and associated trapping states, 2D nanosheets have
      dangling-bond-free surfaces. Thin films created by stacking multiple nanosheets
      have atomically clean van der Waals interfaces and thus promise excellent charge
      transport11-15. However, preparing high-quality solution-processable 2D
      semiconductor nanosheets remains a challenge. For example, MoS2 nanosheets and
      thin films produced using lithium intercalation and exfoliation are plagued by
      the presence of the metallic 1T phase and poor electrical performance (mobilities
      of about 0.3 square centimetres per volt per second and on/off ratios of less
      than 10)2,12, and materials produced by liquid exfoliation exhibit an
      intrinsically broad thickness distribution, which leads to poor film quality and
      unsatisfactory thin-film electrical performance (mobilities of about 0.4 square
      centimetres per volt per second and on/off ratios of about 100)14,16,17. Here we
      report a general approach to preparing highly uniform, solution-processable,
      phase-pure semiconducting nanosheets, which involves the electrochemical
      intercalation of quaternary ammonium molecules (such as tetraheptylammonium
      bromide) into 2D crystals, followed by a mild sonication and exfoliation process.
      By precisely controlling the intercalation chemistry, we obtained phase-pure,
      semiconducting 2H-MoS2 nanosheets with a narrow thickness distribution. These
      nanosheets were then further processed into high-performance thin-film
      transistors, with room-temperature mobilities of about 10 square centimetres per
      volt per second and on/off ratios of 106 that greatly exceed those obtained for
      previous solution-processed MoS2 thin-film transistors. The scalable fabrication
      of large-area arrays of thin-film transistors enabled the construction of
      functional logic gates and computational circuits, including an inverter, NAND,
      NOR, AND and XOR gates, and a logic half-adder. We also applied our approach to
      other 2D materials, including WSe2, Bi2Se3, NbSe2, In2Se3, Sb2Te3 and black
      phosphorus, demonstrating its potential for generating versatile solution
      processable 2D materials.

PMID- 30283140
TI  - Handover mechanism of the growing pilus by the bacterial outer-membrane usher
      FimD.
AB  - Pathogenic bacteria such as Escherichia coli assemble surface structures termed
      pili, or fimbriae, to mediate binding to host-cell receptors1. Type 1 pili are
      assembled via the conserved chaperone-usher pathway2-5. The outer-membrane usher
      FimD recruits pilus subunits bound by the chaperone FimC via the periplasmic N
      terminal domain of the usher. Subunit translocation through the beta-barrel
      channel of the usher occurs at the two C-terminal domains (which we label CTD1
      and CTD2) of this protein. How the chaperone-subunit complex bound to the N
      terminal domain is handed over to the C-terminal domains, as well as the timing
      of subunit polymerization into the growing pilus, have previously been unclear.
      Here we use cryo-electron microscopy to capture a pilus assembly intermediate
      (FimD-FimC-FimF-FimG-FimH) in a conformation in which FimD is in the process of
      handing over the chaperone-bound end of the growing pilus to the C-terminal
      domains. In this structure, FimF has already polymerized with FimG, and the N
      terminal domain of FimD swings over to bind CTD2; the N-terminal domain maintains
      contact with FimC-FimF, while at the same time permitting access to the C
      terminal domains. FimD has an intrinsically disordered N-terminal tail that
      precedes the N-terminal domain. This N-terminal tail folds into a helical motif
      upon recruiting the FimC-subunit complex, but reorganizes into a loop to bind
      CTD2 during handover. Because both the N-terminal and C-terminal domains of FimD
      are bound to the end of the growing pilus, the structure further suggests a
      mechanism for stabilizing the assembly intermediate to prevent the pilus fibre
      diffusing away during the incorporation of thousands of subunits.

PMID- 30283142
TI  - Moving the needle on colorectal cancer genetics: it takes more than two to TANGO.

PMID- 30283143
TI  - Primary constitutional MLH1 epimutations: a focal epigenetic event.
AB  - BACKGROUND: Constitutional MLH1 epimutations are characterised by monoallelic
      methylation of the MLH1 promoter throughout normal tissues, accompanied by allele
      specific silencing. The mechanism underlying primary MLH1 epimutations is
      currently unknown. The aim of this study was to perform an in-depth
      characterisation of constitutional MLH1 epimutations targeting the aberrantly
      methylated region around MLH1 and other genomic loci. METHODS: Twelve MLH1
      epimutation carriers, 61 Lynch syndrome patients, and 41 healthy controls, were
      analysed by Infinium 450 K array. Targeted molecular techniques were used to
      characterise the MLH1 epimutation carriers and their inheritance pattern.
      RESULTS: No nucleotide or structural variants were identified in-cis on the
      epimutated allele in 10 carriers, in which inter-generational methylation erasure
      was demonstrated in two, suggesting primary type of epimutation. CNVs outside the
      MLH1 locus were found in two cases. EPM2AIP1-MLH1 CpG island was identified as
      the sole differentially methylated region in MLH1 epimutation carriers compared
      to controls. CONCLUSION: Primary constitutional MLH1 epimutations arise as a
      focal epigenetic event at the EPM2AIP1-MLH1 CpG island in the absence of cis
      acting genetic variants. Further molecular characterisation is needed to
      elucidate the mechanistic basis of MLH1 epimutations and their
      heritability/reversibility.

PMID- 30283145
TI  - Comment on 'Domestic light at night and breast cancer risk: a prospective
      analysis of 105 000 UK women in the Generations Study'.

PMID- 30283144
TI  - Colon-specific eQTL analysis to inform on functional SNPs.
AB  - BACKGROUND: Genome-wide association studies on colorectal cancer have identified
      more than 60 susceptibility loci, but for most of them there is no clear
      knowledge of functionality or the underlying gene responsible for the risk
      modification. Expression quantitative trail loci (eQTL) may provide functional
      information for such single nucleotide polymorphisms (SNPs). METHODS: We have
      performed detailed eQTL analysis specific for colon tissue on a series of 97
      colon tumours, their paired adjacent normal mucosa and 47 colon mucosa samples
      donated by healthy individuals. R package MatrixEQTL was used to search for
      genome-wide cis-eQTL and trans-eQTL fitting linear models adjusted for age,
      gender and tissue type to rank transformed expression data. RESULTS: The cis-eQTL
      analyses has revealed 29,073 SNP-gene associations with permutation-adjusted P
      values < 0.01. These correspond to 363 unique genes. The trans-eQTL analysis
      identified 10,665 significant SNP-gene associations, most of them in the same
      chromosome, further than 1 Mb of the gene. We provide a web tool to search for
      specific SNPs or genes. The tool calculates Pearson or Spearman correlation, and
      allows to select tissue type for analysis. Data and plots can be exported.
      CONCLUSIONS: This resource should be useful to prioritise SNPs for further
      functional studies and to identify relevant genes behind identified loci.

PMID- 30283146
TI  - Parallel phylogeography of Prochlorococcus and Synechococcus.
AB  - The globally abundant marine Cyanobacteria Prochlorococcus and Synechococcus
      share many physiological traits but presumably have different evolutionary
      histories and associated phylogeography. In Prochlorococcus, there is a clear
      phylogenetic hierarchy of ecotypes, whereas multiple Synechococcus clades have
      overlapping physiologies and environmental distributions. However, microbial
      traits are associated with different phylogenetic depths. Using this principle,
      we reclassified diversity at different phylogenetic levels and compared the
      phylogeography. We sequenced the genetic diversity of Prochlorococcus and
      Synechococcus from 339 samples across the tropical Pacific Ocean and North
      Atlantic Ocean using a highly variable phylogenetic marker gene (rpoC1). We
      observed clear parallel niche distributions of ecotypes leading to high Pianka's
      Index values driven by distinct shifts at two transition points. The first
      transition point at 6 degrees N distinguished ecotypes adapted to warm waters but
      separated by macronutrient content. At 39 degrees N, ecotypes adapted to warm,
      low macronutrient vs. colder, high macronutrient waters shifted. Finally, we
      detected parallel vertical and regional single-nucleotide polymorphism
      microdiversity within clades from both Prochlorococcus and Synechococcus,
      suggesting uniquely adapted populations at very specific depths, as well as
      between the Atlantic and Pacific Oceans. Overall, this study demonstrates that
      Prochlorococcus and Synechococcus have shared phylogenetic organization of traits
      and associated phylogeography.

PMID- 30283147
TI  - LEAM versus CBV for conditioning in autologous hematopoietic stem cell
      transplantation for lymphoma.

PMID- 30283148
TI  - Current use of biosimilar G-CSF for haematopoietic stem cell mobilisation.
AB  - Despite biosimilars of the granulocyte-colony stimulating factor (G-CSF)
      filgrastim being approved by the European Medicines Agency since 2008, there is
      still some debate regarding their use in related and unrelated healthy
      haematopoietic stem cell donors. We present a review of published experiences
      using biosimilar filgrastim for healthy donor mobilisation as well as the results
      of a survey by the World Marrow Donor Association (WMDA) of its current use by
      register-associated transplant and collection centres for both related and
      unrelated donors. A total of 1287 healthy donors and volunteers are included in
      the reviewed studies. The pharmacokinetics and pharmacodynamics studies show a
      high degree of similarity to the reference product Neupogen. Mobilisation of CD34
      + cells as well as reported adverse events are also found to be comparable,
      although there is still a lack of long-term follow up for both Neupogen and
      filgrastim biosimilars. No evidence is found of a higher risk of filgrastim
      antibody formation using filgrastim biosimilars. Based on this increased
      experience, the WMDA therefore recommend that Stem Cell Donor Registries can use
      filgrastim biosimilars for the mobilisation of peripheral blood progenitor cells
      in healthy donors, provided that they are approved by national and/or regional
      agencies.

PMID- 30283141
TI  - Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris.
AB  - Here we present a compendium of single-cell transcriptomic data from the model
      organism Mus musculus that comprises more than 100,000 cells from 20 organs and
      tissues. These data represent a new resource for cell biology, reveal gene
      expression in poorly characterized cell populations and enable the direct and
      controlled comparison of gene expression in cell types that are shared between
      tissues, such as T lymphocytes and endothelial cells from different anatomical
      locations. Two distinct technical approaches were used for most organs: one
      approach, microfluidic droplet-based 3'-end counting, enabled the survey of
      thousands of cells at relatively low coverage, whereas the other, full-length
      transcript analysis based on fluorescence-activated cell sorting, enabled the
      characterization of cell types with high sensitivity and coverage. The cumulative
      data provide the foundation for an atlas of transcriptomic cell biology.

PMID- 30283149
TI  - Multivalent and multifunctional polysaccharide-based particles for controlled
      receptor recognition.
AB  - Polysaccharides represent a versatile class of building blocks that are used in
      macromolecular design. By choosing the appropriate saccharide block, various
      physico-chemical and biological properties can be introduced both at the level of
      the polymer chains and the resulting self-assembled nanostructures. Here, we
      synthetized amphiphilic diblock copolymers combining a hydrophobic and helical
      poly(gamma-benzyl-L-glutamate) PBLG and two polysaccharides, namely hyaluronic
      acid (HA) and laminarin (LAM). The copolymers could self-assemble to form
      particles in water by nanoprecipitation. In addition, hybrid particles containing
      both HA and LAM in different ratios were obtained by co-nanoprecipitation of the
      two copolymers. By controlling the self-assembly process, five particle samples
      with different morphologies and compositions were developed. The interaction
      between the particles and biologically relevant proteins for HA and LAM, namely
      CD44 and Dectin-1 respectively, was evaluated by surface plasmon resonance (SPR).
      We demonstrated that the particle-protein interaction could be modulated by the
      particle structure and composition. It is therefore suggested that this method
      based on nanoprecipitation is a practical and versatile way to obtain particles
      with controllable interactions with proteins, hence with the appropriate
      biological properties for biomedical applications such as drug delivery.

PMID- 30283150
TI  - A novel design to screen chlorogenic acid-producing microbial strains from the
      environment.
AB  - The present study aimed to develop a plate-screening method, based on the
      specific color development of complexes formed between chlorogenic acid, a
      valuable plant-derived compound, and aluminum (III), to detect chlorogenic acid
      producing microbial strains. Modified media with 0.75 mM aluminum chloride were
      developed to identify CGA-producing bacteria (based on beef extract agar medium)
      or fungi (based on the potato dextrose agar medium). Compared with conventional
      screening, the modified media let to 3.3 times more CGA producers from plants, at
      90.9% selective accuracy. Novel chlorogenic acid-biosynthesizing strains included
      Brevibacillus borstelensis B14, Bacillus amyloliquefaciens B17, Bacillus badius
      B19, Sphingomonas yabuuchiae N21, Enterobacter tabaci N22, and Lodderomyces
      elongisporus S216 and P212. Strain S216 produced the highest chlorogenic acid
      yield (23.39 mg L-1). This study provides a highly efficient and low-cost tool
      for quick detection and subsequent identification of several newly isolated
      strains with chlorogenic acid-producing potential.

PMID- 30283152
TI  - Modeling the two- and three-dimensional displacement field in Lorca, Spain,
      subsidence and the global implications.
AB  - Land subsidence associated with overexploitation of aquifers is a hazard that
      commonly affects large areas worldwide. The Lorca area, located in southeast
      Spain, has undergone one of the highest subsidence rates in Europe as a direct
      consequence of long-term aquifer exploitation. Previous studies carried out on
      the region assumed that the ground deformation retrieved from satellite radar
      interferometry corresponds only to vertical displacement. Here we report, for the
      first time, the two- and three-dimensional displacement field over the study area
      using synthetic aperture radar (SAR) data from Sentinel-1A images and Global
      Navigation Satellite System (GNSS) observations. By modeling this displacement,
      we provide new insights on the spatial and temporal evolution of the subsidence
      processes and on the main governing mechanisms. Additionally, we also demonstrate
      the importance of knowing both the vertical and horizontal components of the
      displacement to properly characterize similar hazards. Based on these results, we
      propose some general guidelines for the sustainable management and monitoring of
      land subsidence related to anthropogenic activities.

PMID- 30283153
TI  - The translation of age-related body composition findings from rodents to humans.
AB  - The objective of this review is to highlight changes in body composition in
      rodent models as a result of healthy aging in order to enhance translational
      research. Aging is associated with alterations in body composition, particularly
      fat mass and fat-free mass, which may be accompanied by adverse health effects,
      especially nearing middle age to old age. In humans, it is generally understood
      that fat mass tends to increase while fat-free mass concurrently declines with
      aging. However, the effect of aging on body composition in rodent models is less
      well studied, and how these changes compare and contrast with observations in
      humans has not yet been fully elucidated. Though, it appears as though the
      constituent-level alterations occur in humans and rodents at different life
      phases thereby having a potential effect on the outcomes of basic biomedical
      research. Though highly strain-dependent, this review suggests that FM changes
      begin at a much earlier life phase in rodents than in humans. Conversely, FFM
      appears to increase throughout middle age and into old age in rodents, whereas
      middle age is associated with the initiation the subsequent decline of FFM in
      humans. Given the essentiality of rodent models in basic biomedical research,
      careful consideration of these differences in age-related BC findings is
      imperative when the research is aimed for human translation.

PMID- 30283151
TI  - Photosystem-II D1 protein mutants of Chlamydomonas reinhardtii in relation to
      metabolic rewiring and remodelling of H-bond network at QB site.
AB  - Photosystem II (PSII) reaction centre D1 protein of oxygenic phototrophs is
      pivotal for sustaining photosynthesis. Also, it is targeted by herbicides and
      herbicide-resistant weeds harbour single amino acid substitutions in D1.
      Conservation of D1 primary structure is seminal in the photosynthetic performance
      in many diverse species. In this study, we analysed built-in and environmentally
      induced (high temperature and high photon fluency - HT/HL) phenotypes of two D1
      mutants of Chlamydomonas reinhardtii with Ala250Arg (A250R) and Ser264Lys (S264K)
      substitutions. Both mutations differentially affected efficiency of electron
      transport and oxygen production. In addition, targeted metabolomics revealed that
      the mutants undergo specific differences in primary and secondary metabolism,
      namely, amino acids, organic acids, pigments, NAD, xanthophylls and carotenes.
      Levels of lutein, beta-carotene and zeaxanthin were in sync with their
      corresponding gene transcripts in response to HT/HL stress treatment in the
      parental (IL) and A250R strains. D1 structure analysis indicated that, among
      other effects, remodelling of H-bond network at the QB site might underpin the
      observed phenotypes. Thus, the D1 protein, in addition to being pivotal for
      efficient photosynthesis, may have a moonlighting role in rewiring of specific
      metabolic pathways, possibly involving retrograde signalling.

PMID- 30283154
TI  - Clara cells protein, prolactin and transcription factors of protein NF-KB and c
      Jun/AP-1 levels in rats inhaled to stainless steel welding dust and its soluble
      form.
AB  - OBJECTIVES: Welding processes that generate fumes containing toxic metals, such
      as hexavalent chromium (Cr(VI)), manganese, and nickel (Ni), have been implicated
      in lung injury, inflammation, and lung tumor promotion in animal models.
      Bronchiolar epithelium Clara cells/club cells, coordinate these inflammatory
      responses. Clara cells secretory protein (CC16) with ant-inflammatory role.
      MATERIAL AND METHODS: The pulmonary toxicity of welding dust (WD) was assessed
      for Wistar rats exposed to 60 mg/m<sup>3</sup> of respirable-size welding dust
      (mean diameter 1.17 MUm for 1 and 2 weeks (6 h/day, 5 days/week)) or the aerosols
      of soluble form (SWD) in the nose-only exposure chambers. Additionally the effect
      of antiinflammatory betaine supplementation was assessed. Clara cells secretory
      protein, differential cell counts, total protein concentrations and cellular
      enzyme (lactate dehydrogenase - LDH) activities were determined in
      bronchoalveolar lavage fluid, and corticosterone and thiobarbituric acid reactive
      substances (TBARS) and prolactin concentrations were assessed in serum.
      Histopathology examination of lung, brain, liver, kidney, spleen was done.
      Additionally slices of brain and lung were exanimated in laser ablation
      inductively coupled plasma mass spectrometry. RESULTS: Both WD and SWD exposure
      evoked large bronchiolar infiltration shoved in histopathology examination. In
      this study, TBARS inversely correlated with a significant decrease of CC16
      concentration that occurred after instillation of both WD and SWD indicating
      decreased anti- inflammatory potential in the lung. In WD exposed rats prolactin
      correlated with nuclear factor-kappa B (NF-kappaB), LDH, TBARS and serum levels
      Cr, Ni and inversely with c-Jun. In SWD exposed rats prolactin correlated with
      CC16 indicated effect of prolactin on the population of epithelial cells.
      CONCLUSIONS: In the current study, deleterious effects of repeated inhalation
      stainless steel welding dust form on club (Clara) cell secretory protein (CC16)
      were demonstrated. Clara cells secretory protein relation with prolactin in
      exposed rats to welding dust were shown and explored whether the NF-kappaB and c
      Jun/activator protein 1 related pathway was involved. Int J Occup Med Environ
      Health 2018;31(5):613-632.

PMID- 30283155
TI  - Acoustic source localization with microphone arrays for remote noise monitoring
      in an Intensive Care Unit.
AB  - An approach is described to apply spatial filtering with microphone arrays to
      localize acoustic sources in an Intensive Care Unit (ICU). This is done to obtain
      more detailed information about disturbing noise sources in the ICU with the
      ultimate goal of facilitating the reduction of the overall background noise
      level, which could potentially improve the patients' experience and reduce the
      time needed for recovery. This paper gives a practical description of the system,
      including the audio hardware setup as well as the design choices for the
      microphone arrays. Additionally, the necessary signal processing steps required
      to produce meaningful data are explained, focusing on a novel clustering approach
      that enables an automatic evaluation of the spatial filtering results. This
      approach allows the data to be presented to the nursing staff in a way that
      enables them to act on the results produced by the system.

PMID- 30283156
TI  - Spatio-temporal modelling as a way to reconstruct patterns of past human
      activities.
AB  - This paper examines the possibilities of creating quantified models of past human
      activities in both time and space. The study area lies in the southeastern Czech
      Republic and western Slovakia. The spatio-temporal model of behavioural
      categories was calculated with the help of Monte Carlo simulations and
      statistical testing. One of the main advantages of our approach is that it admits
      the probabilistic nature of input data, quantifies them and provides
      probabilistic results comparable with other proxies. It also presents a less
      biased way of how archaeological data from regions and periods with low numbers
      of 14C datings can be incorporated into models of past population dynamics.

PMID- 30283157
TI  - Feature selection by optimizing a lower bound of conditional mutual information.
AB  - A unified framework is proposed to select features by optimizing computationally
      feasible approximations of high-dimensional conditional mutual information (CMI)
      between features and their associated class label under different assumptions.
      Under this unified framework, state-of-the-art information theory based feature
      selection algorithms are rederived, and a new algorithm is proposed to select
      features by optimizing a lower bound of the CMI with a weaker assumption than
      those adopted by existing methods. The new feature selection method integrates a
      plug-in component to distinguish redundant features from irrelevant ones for
      improving the feature selection robustness. Furthermore, a novel metric is
      proposed to evaluate feature selection methods based on simulated data. The
      proposed method has been compared with state-of-the-art feature selection methods
      based on the new evaluation metric and classification performance of classifiers
      built upon the selected features. The experiment results have demonstrated that
      the proposed method could achieve promising performance in a variety of feature
      selection problems.

PMID- 30283158
TI  - Odd-even effect on the formation of aqueous biphasic systems formed by 1-alkyl-3
      methylimidazolium chloride ionic liquids and salts.
AB  - This work provides a comprehensive evaluation of the effect of the cation alkyl
      side chain length of the 1-alkyl-3-methylimidazolium chloride series ([C n
      C1im]Cl, n = 2-14) of ionic liquids (ILs) on their capability to form aqueous
      biphasic systems (ABSs) with salts and self-aggregation derived properties. The
      liquid-liquid phase behavior of ternary systems composed of [C n C1im]Cl, water,
      and K3PO4 or K2CO3 and the respective Setschenow salting-out coefficients (ks ),
      a quantitative measure of the two-phase formation ability, were determined. An
      odd-even effect in the ks values along the number of methylene groups of the
      longest IL cation alkyl side chain was identified for the ABS formed by K2CO3, a
      weaker salting-out agent where the phenomenon is clearly identified. In general,
      cations with even alkyl side chains, being likely to display higher molar
      volumes, are more easily salted-out and thus more prone to undergo phase
      separation. The odd-even effect in the ks values is, however, more significant in
      ILs up to n = 6, where the nanostructuration/nanosegregation of ILs plays a less
      relevant role. Still, with the [C n C1im]Cl (n = 7-14) series of ILs, an odd-even
      effect was also identified in the ILs' ionization degree, molar conductivity, and
      conductivity at infinite dilution. In summary, it is shown here that the ILs' odd
      even effect occurs in IL aqueous solutions and not just in neat ILs, an already
      well-established phenomenon occurring in a series of ILs' properties described as
      a result of the orientation of the terminal methyl groups to the imidazolium ring
      cation and consequent effect in the ILs' cohesive energy.

PMID- 30283159
TI  - Projecting potential spatial and temporal changes in the distribution of
      Plasmodium vivax and Plasmodium falciparum malaria in China with climate change.
AB  - Background: Global climate change is likely to increase the geographic range and
      seasonality of malaria transmission. Areas suitable for distribution of malaria
      vectors are predicted to increase with climate change but evidence is limited on
      future distribution of malaria with climate in China. Objective: Our aim was to
      assess a potential effect of climate change on Plasmodium vivax (P. vivax) and
      Plasmodium falciparum (P. falciparum) malaria under climate change scenarios.
      Methods: National malaria surveillance data during 2005-2014 were integrated with
      corresponding climate data to model current weather-malaria relationship. We used
      the Generalized Additive Model (GAM) with a spatial component, assuming a quasi
      Poisson distribution and including an offset for the population while accounting
      for potential non-linearity and long-term trend. The association was applied to
      future climate to project county-level malaria distribution using ensembles of
      Global Climate Models under two climate scenarios - Representative Concentration
      Pathways (RCP4.5 and RCP8.5). Results: Climate change could substantially
      increase P. vivax and P. falciparum malaria, under both climate scenarios, but by
      larger amount under RCP8.5, compared to the baseline. P. falciparum is projected
      to increase more than P. vivax. The distributions of P. vivax and P. falciparum
      malaria are expected to increase in most regions regardless of the climate
      scenarios. A high percentage (>50%) increases are projected in some counties of
      the northwest, north, northeast, including northern tip of the northeast China,
      with a clearer spatial change for P. vivax than P. falciparum under both
      scenarios, highlighting potential changes in the latitudinal extent of the
      malaria. Conclusion: Our findings suggest that spatial and temporal distribution
      of P. vivax and P. falciparum malaria in China will change due to future climate
      change, if there is no policy to mitigate it. These findings are important to
      guide the malaria elimination goal for China.

PMID- 30283161
TI  - Soil organic matter widens the range of water contents for tillage.
AB  - The effects of soil organic matter on the water contents for tillage were
      investigated by sampling soils with a uniform texture, but a range of soil
      organic carbon (SOC) from two long-term field experiments at Highfield in
      Rothamsted Research, UK and Askov Experimental Station, Denmark. The treatments
      studied in Highfield were Bare fallow (BF), Continuous arable rotation (A), Ley
      arable (LA) and Grass (G); and in Askov: unfertilized (UNF), 1/2 mineral
      fertilizer (1/2 NPK), 1 mineral fertilizer (1NPK), and 11/2 animal manure
      (11/2AM). Minimally disturbed soil cores (100 cm3) were sampled per plot in both
      locations from 6 to 10 cm depth to generate water retention data. Soil blocks
      were also sampled at 6-15 cm depth to determine basic soil properties and to
      measure soil aggregate strength parameters. The range of soil water contents
      appropriate for tillage were determined using the water retention and the
      consistency approaches. SOC content in Highfield was in the order: G > LA = A >
      BF, and in Askov: 11/2 AM > 1NPK = 1/2NPK > UNF. Results showed that different
      long-term management of the silt loam Highfield soil, and fertilization of the
      sandy loam Askov soil affected the mechanical properties of the soils- for
      Highfield soil, aggregates from the G treatment were stronger in terms of rupture
      energy when wet (-100 hPa matric potential) than the BF treatment. As the soil
      dried (-300 and -1000 hPa matric potentials), soil aggregates from the G
      treatment were relatively weaker and more elastic than the BF soil. Our study
      showed, for both Highfield and Askov soils, a strong positive linear increase in
      the range of water contents for tillage with increasing contents of SOC. This
      suggests that management practices leading to increased SOC can improve soil
      workability by increasing the range of water contents for tillage. We recommended
      using the consistency approach over the water retention approach for determining
      the range of water contents for tillage because it seems to give realistic
      estimates of the water contents for tillage.

PMID- 30283163
TI  - Nepotism in Publication of Medical Literature! Does It Exist? May Be It Does!!

PMID- 30283162
TI  - Examining affective structure in chickens: valence, intensity, persistence and
      generalization measured using a Conditioned Place Preference Test.
AB  - When measuring animals' valenced behavioural responses to stimuli, the
      Conditioned Place Preference (CPP) test goes a step further than many approach
      based and avoidance-based tests by establishing whether a learned preference for,
      or aversion to, the location in which the stimulus was encountered can be
      generated. We designed a novel, four-chambered CPP test to extend the capability
      of the usual CPP paradigm to provide information on four key features of animals'
      affective responses: valence, scale, persistence and generalization. Using this
      test, we investigated the affective responses of domestic chickens (Gallus gallus
      domesticus) to four potentially aversive stimuli: 1. Puffs of air; 2. Sight of
      (robotic) snake; 3. Sprays of water; 4. Sound of conspecific alarm calls. We
      found conditioned avoidance of locations associated with the air puffs and water
      sprays (Friedman's chi2 (3) = 13.323 p > .005; chi2 (3) = 14.235 p > .005), but
      not with the snake and alarm calls. The scale of the learned avoidance was
      similar for the air puff and water spray stimuli, but persistence and
      generalization differed. We conclude that the four chambered CPP test can have a
      valuable role to play in making multi-feature measurements of stimulus-generated
      affective responses, and we highlight the value of such measurements for
      improving our understanding of the structure of affect in chickens and other
      animals.

PMID- 30283160
TI  - Reactive oxygen species, oxidative signaling and the regulation of
      photosynthesis.
AB  - Reduction-oxidation (redox) reactions, in which electrons move from a donor to an
      acceptor, are the functional heart of photosynthesis. It is not surprising
      therefore that reactive oxygen species (ROS) are generated in abundance by
      photosynthesis, providing a plethora of redox signals as well as functioning as
      essential regulators of energy and metabolic fluxes. Chloroplasts are equipped
      with an elaborate and multifaceted protective network that allows photosynthesis
      to function with high productivity even in resource-limited natural environments.
      This includes numerous antioxidants with overlapping functions that provide
      enormous flexibility in redox control. ROS are an integral part of the repertoire
      of chloroplast signals that are transferred to the nucleus to convey essential
      information concerning redox pressure within the electron transport chain.
      Current evidence suggests that there is specificity in the gene-expression
      profiles triggered by the different ROS signals, so that singlet oxygen triggers
      programs related to over excitation of photosystem (PS) II while superoxide and
      hydrogen peroxide promote the expression of other suites of genes that may serve
      to alleviate electron pressure on the reducing side of PSI. Not all chloroplasts
      are equal in their signaling functions, with some sub-populations appearing to
      have better contacts/access to the nucleus than others to promote genetic and
      epigenetic responses. While the concept that light-induced increases in ROS
      result in damage to PSII and photoinhibition is embedded in the photosynthesis
      literature, there is little consensus concerning the extent to which such
      oxidative damage happens in nature. Slowly reversible decreases in photosynthetic
      capacity are not necessarily the result of light-induced damage to PSII reaction
      centers.

PMID- 30283164
TI  - Possible Bias in the Publication Trends of High Impact Factor Anesthesiology and
      Gastroenterology Journals -An Analysis of 5 Years' Data.
AB  - Background: We hypothesize that being an editorial board member (EBM) in a high
      impact factor specialty medical journal increases the chances of publishing in
      the same journal. Materials and Methods: The publication trends of the first five
      EBMs in the five highest impact factor Anesthesiology and Gastroenterology
      journals were analyzed. Preceding 5 years' publications appearing on PubMed were
      grouped into as follows: number of publications in the journal in which the EBM
      serves (N1), number of publications by the same author in the other four highest
      impact factor (IF) journals (N2) and number of publications in all the other
      journals (N3). We evaluated the probability of the observed distribution of
      publications in the five highest IF journals happening by chance alone, assuming
      that all the EBMs had the same opportunity of publishing in any of these
      journals. The probability of publishing in their own journal was assumed to be
      one fifth. Results: The EBMs published their manuscripts in their own journal at
      a very high frequency. Encompassing all ten journals, the calculated P value for
      such a distribution was <0.001. In two journals, Anesthesia and Analgesia and
      Anaesthesia, the EBMs' publications in their journal were more than twice the
      cumulative total in the remaining four journals. In three of the five
      gastroenterology journals analyzed, combined publications of the five EBMs were
      greater in their own journal than the remaining four journals combined.
      Conclusions: Despite proclaimed fair peer review process, EBMs seem to get
      preference in their own journals.

PMID- 30283165
TI  - Intraoperative Meditation Music as an Adjunct to Subarachnoid Block for the
      Improvement of Postoperative Outcomes Following Cesarean Section: A Randomized
      Placebo-controlled Comparative Study.
AB  - Context: Music therapy is a nonpharmacological modality which can provide
      promising results for postcesarean section recovery. Aims: The aim of this study
      was to compare the effects of two types of intraoperative meditation music with
      control group on postcesarean section pain, anxiety, nausea, vomiting, and
      psychological maternal wellbeing. Settings and Design: A prospective, randomized,
      controlled study was conducted on 189 patients. Patients and Methods: The
      inclusion criteria were the American Society of Anaesthesiologists physical
      status classes 1E and 2E women aged over 18 years posted for emergency cesarean
      section under spinal anesthesia. The exclusion criteria were patients with
      hearing/ear abnormalities and psychiatric disorders. Patients were randomly
      allocated into three groups - soothing meditation music (M) group, binaural beat
      meditation music (B) group, and control (C) group - where no music was played.
      After intervention, data were collected and statistically analyzed. Statistical
      Analysis Used: Student's t-test was applied for calculation of normative
      distribution and Mann-Whitney U-test for nonnormative distribution. Nominal
      categorical data between the groups were compared using Chi-squared test. P <0.05
      indicated a statistically significant difference. Results: Both intraoperative
      meditation music groups had statistically significant less postoperative pain and
      anxiety and a better overall psychological wellbeing as compared to the control.
      There was no statistically significant difference in the occurrence and severity
      of postoperative nausea and vomiting across all three groups. Conclusions:
      Intraoperative meditation music as good adjunct to spinal anesthesia can improve
      a cesarean section patient's postoperative experience by reducing postoperative
      pain, anxiety, and psychological wellbeing.

PMID- 30283166
TI  - Inhalation of Ketamine in Different Doses to Decrease the Severity of
      Postoperative Sore Throat in Surgeries under General Anesthesia Patients.
AB  - Context: Postoperative sore throat (POST) occurs in 21%-65% of patients.
      Nebulization of ketamine reduces POST. Aims: The aim of this study is to see the
      effectiveness of nebulized ketamine in different doses to reduce POST and observe
      adverse effects, if any. Settings and Design: This was a prospective, randomized,
      and double-blind controlled trial. One hundred and fifty patients of the American
      Society of Anesthesiologists physical status Classes I and II, in the age group
      of 18-60 years, of either sex, undergoing surgery under general anesthesia were
      randomized into three groups. Subjects and Methods: Patients had nebulized with 5
      ml solution (Group K1 - 1 ml of ketamine [50 mg/ml] +4 ml normal saline, Group K2
      - 0.5 ml of ketamine [50 mg/ml] +4.5 normal saline, and Group S - 5 ml normal
      saline). Preoperative, intraoperative, and postoperative hemodynamic monitoring
      was done. The POST monitoring was done at 2, 4, 8, 12, and 24 h postoperatively.
      POST was graded on a four-point scale (0-3). Statistical Analysis Used: Chi
      square test using MSTAT software for POST and ANOVA test using INDOSTAT software
      for hemodynamics were used in this study. Results: The overall incidence of POST
      in the present study was 29.33% (44/150). In Group S, the incidence of POST was
      observed to be 46% (23/50). In Group K1, the incidence was 20% (10/50), and in
      Group K2, it was 22% (11/50) (P <= 0.05), and intraoperative vital signs were
      more stable at all time intervals. Conclusions: We concluded that both doses (25
      and 50 mg) of nebulized ketamine were almost equally effective in preventing
      POST, with no adverse effects.

PMID- 30283167
TI  - Comparison of Postoperative Quality of Recovery and Pain Relief with Preoperative
      Single-Dose Dexamethasone and Lignocaine after Laparoscopic Cholecystectomy.
AB  - Aim: To compare the role of single intravenous (IV) bolus of lignocaine and
      dexamethasone on pain score and quality of recovery score (QoR40) after
      laparoscopic cholecystectomy. Setting and Design: The study was conducted at the
      postoperative recovery area, This was a double-blind randomized controlled study.
      Materials and Methods: Seventy patients 18-60 years of age, American Society of
      Anesthesiologists physical status Class I and II, who underwent elective
      laparoscopic cholecystectomy, were enrolled in this study after approval from the
      Institutional Ethics Committee. Patients were randomly allocated to two groups.
      Group 1 received: 2 mg/kg lignocaine diluted to 10 ml with normal saline, and
      Group 2 received 0.1 mg/kg IV dexamethasone diluted to 10 ml with normal saline.
      Global QoR-40 is a 40-item questionnaire that provides a global score and
      subscores across five dimensions: psychological support, comfort, independence,
      pain, and emotions. It was assessed on a preoperative day as baseline to assess
      patient's basic quality of life and at 24 h postoperative. Visual analog scale
      (VAS) static and dynamic, total analgesic consumption in a day, nausea and
      vomiting, and antiemetic per day were assessed. Statistical Analysis Used:
      Student's t-test, Chi-square test, Fisher's exact, Levene's test were used for
      statistical analysis. Results: Dexamethasone group had higher Global QoR-40 than
      lignocaine group 187.94 versus 182.85. Among dimensions of QoR-40, dexamethasone
      had statistically better physical comfort, physical independence, and pain relief
      as compared to lignocaine. Dexamethasone group had lower VAS compared to
      lignocaine group. Similarly, there was less fentanyl consumption in dexamethasone
      group (364.08 +/- 127.31) in the postoperative period when compared to the
      lignocaine group (412.31 +/- 147.8). Conclusions: Preoperative administration of
      a single dose of dexamethasone enhanced QoR after laparoscopic cholecystectomy as
      compared to lignocaine bolus dose.

PMID- 30283168
TI  - Comparison of Palonosetron with Granisetron for Prevention of Postoperative
      Nausea and Vomiting in Patients Undergoing Laparoscopic Abdominal Surgery.
AB  - Background: In patients undergoing laparoscopic surgeries, postoperative nausea
      and vomiting (PONV) is a serious concern. With an incidence of 46%-72%, PONV
      hampers the postoperative recovery in spite of the availability of many
      antiemetic drugs. The purpose of this study was to prospectively evaluate the
      efficacy of palonosetron and granisetron for the prevention of PONV in patients
      undergoing laparoscopic abdominal surgery. Aims: The aim of this study was to
      evaluate and compare the efficacy of palonosetron and granisetron in preventing
      PONV and to compare the duration of action and side effects in patients
      undergoing laparoscopic abdominal surgery under general anesthesia. Settings and
      Design: Eighty patients who were comparable in all aspects were considered for
      this study. After their consent, they participated in this prospective,
      randomized, double-blinded, comparative study. Materials and Methods: In this
      observational study, 80 patients of either gender who were undergoing
      laparoscopic abdominal surgery under general anesthesia were enrolled in the
      study. Based on computer randomization, these patients were divided equally into
      two groups of 40 patients each in double-blinded manner. The treatments were
      given intravenously 5 min before induction of anesthesia. The episodes of PONV,
      severity of nausea/vomiting, and side effects were observed during the first 48 h
      after surgery. Statistical Tests: At the end of study, results were compiled and
      SPSS(r) statistical package version 18.0 (SPSS Inc., Chicago, IL, USA). Two
      independent samples t-test was used for quantitative data, and Chi-square or
      Fisher's exact test was used for qualitative data. P < 0.05 was considered
      significant. Results: The incidence of PONV during 0-2 h in the postoperative
      period was 15% with palonosetron and 27.5% with granisetron; the incidence during
      2-24 h postoperatively was 20% with palonosetron and 30% with granisetron. Both
      palonosetron and granisetron had comparable effectiveness as antiemetic during
      the early postoperative periods (0-24 h). During 24-48 h, the incidence was 17.5%
      and 37.5%, respectively (P = 0.04). Safety profile was similar in both the groups
      (P = 0.6). Conclusion: There were no significant differences in the overall
      incidence of PONV and complete responders for palonosetron and granisetron group
      in the early recovery period. However, due to its prolonged duration of action,
      palonosetron was more effective than granisetron for long-term prevention of PONV
      after laparoscopic abdominal surgery.

PMID- 30283169
TI  - Caudal Analgesia for Hypospadias in Pediatrics: Comparative Evaluation of
      Adjuvants Dexamethasone and Dexmedetomidine Combination versus Dexamethasone or
      Dexmedetomidine to Bupivacaine: A Prospective, Double-Blinded, Randomized
      Comparative Study.
AB  - Background: Caudal block is the most commonly used regional anesthetic technique
      in pediatric surgeries; different additives have been used for better and safer
      outcome. Aim: The aim of this study is to compare the combination of
      dexamethasone and dexmedetomidine as adjuvants to bupivacaine versus using each
      agent solely with bupivacaine in pediatric caudal block as regards their
      efficiency in pain relief (the duration of postoperative analgesia, first time to
      request analgesia, and modified objective pain score [MOPS]). Study Design: This
      was a prospective, double-blinded, randomized study. Patients and Methods:
      Patients and Methods: Sixty-three children scheduled for hypospadias surgery
      wererandomized into three groupsaccording to the adjuvant drug added to caudal
      bupivacaine : Group I (n = 21): dexamethasone 0.1 mg/kg + 0.5 mg/kg bupivacaine
      0.25%, Group II (n = 21): dexmedetomidine0.01 MUg/kg + 0.5 mg/kg bupivacaine
      0.25% and Group III (n = 21): dexamethasone 0.1 mg/kg + dexmedetomidine 0.01
      MUg/kg + 0.5 mg/kgbupivacaine 0.25%. Intraoperative and postoperative
      hemodynamics were recorded. In postoperative anesthesia care unit and then the
      ward, MOPS and sedation score were recorded at 30 min and 1, 2, 3, 6 and 12 h.
      Further, the time of first analgesic request and side effects were recorded.
      Statistical Analysis: Categorical data were presented as frequencies (%) and
      analyzed using Chi-square test. Continuous data were presented as mean (standard
      deviation) and median (quartiles). Continuous data were analyzed using one-way
      analysis of variance for single measures and two-way mixed model for repeated
      measures. Kaplan-Meier analysis was performed for the duration of analgesia.
      Results: In Group III, MOPS was lower than Groups I and II at the study times.
      Further, Group III had prolonged time for first request of analgesic. Sedation
      scores were prolonged in Group III and Group II than in Group I. There was a
      reduction in heart rates in Group III more than Group I and Group II but with no
      significant difference. However, there was a significant reduction in mean
      arterial blood pressure 30 min intraoperatively and postoperatively in Group III
      as compared to Groups I and II. Conclusion: The addition of combined
      dexmedetomidine at a dose of 1 MUg/kg and dexamethasone 0.1 mg/kg to caudal
      bupivacaine seemed to be an attractive alternative to each drug if used alone
      with more prolonged analgesia and almost no adverse effects.

PMID- 30283170
TI  - Practice of Labor Analgesia among Anesthesiologists Across India: Cross-sectional
      Study.
AB  - Background: The practice of labor analgesia is an essential part of standard
      obstetric care. There are many guidelines and programs, which have been setup in
      labor pain management, in the developed country. In India, the practice of labor
      analgesia is not very popular. The role of labor analgesia providers lies in
      educating the parturients about the need of labor analgesia and also to develop
      comprehensive programs and guidelines in providing it. Aim: The aim of our study
      was to assess knowledge and practice of labour analgesia among anaesthesiologists
      across India. Methods: Survey was carried out using SurveyMonkey, an online
      internet website. Questionnaires were sent by mail to 11,986 anesthesiologists.
      The questions were based on methods of labor analgesia practice, regional
      analgesia techniques, commonly used drugs, complications and myths surrounding
      labor analgesia. Statistical Analysis: Responses were compiled and data was
      analysed. Results were expressed as percentages. Results: There were 1351
      responses to the survey. Labor analgesia was practiced mainly by
      anesthesiologists across India (71.34%, n = 945). Regional analgesia techniques
      were the most common techniques followed in providing labor analgesia (69.61%, n
      = 940) and among regional analgesia techniques, epidural analgesia (43.52%, n =
      588) was the most common method. Bupivacaine was considered the drug of choice
      (64.10% n = 866) and Fentanyl was the standard adjuvant used (83.34% n = 1126).
      Majority of the respondents did not believe in myths surrounding labor analgesia.
      Conclusion: Epidural analgesia is the most common technique practiced,
      bupivacaine the commonly used local anaesthetic, fentanyl common adjuvant used in
      practice of labour analgesia by anaesthesiologists across India.

PMID- 30283171
TI  - Comparison of Effects of Oral Melatonin with Oral Alprazolam used as a
      Premedicant in Adult Patients Undergoing Various Surgical Procedures under
      General Anesthesia: A Prospective Randomized Placebo-Controlled Study.
AB  - Background and Aims: Preoperative anxiety is a major concern in patients
      undergoing any surgical procedure. Various drugs have been used to alleviate it.
      This study aims to compare the effects of oral melatonin versus oral alprazolam
      on preoperative anxiety, sedation, orientation, and cognitive function. Materials
      and Methods: A total of 90 adult patients were randomly allocated into three
      groups. Group M (n = 30) received oral melatonin 3 mg (2 tablets); Group A (n =
      30) received oral alprazolam 0.25 mg (2 tablets), and Group P (n = 30) received
      placebo, multivitamin tablet (2 tablets) as premedication. The objectives of our
      study were to compare anxiety, sedation, orientation, and cognitive function
      using visual analog scale (VAS) anxiety score, Ramsay Sedation Score (RSS),
      orientation score, and Digit symbol substitution test (DSST) score before and
      after 120 min of giving premedication. For statistical analysis, paired t-test,
      Chi-square test, analysis of variance, and post hoc bonferroni test were used.
      Results: Mean VAS scores for anxiety (after 120 min) were significantly reduced
      in Group M (3.9 +/- 1.53) and Group A (4.43 +/- 1.67) when compared to Group P
      (4.73 +/- 0.82) (P < 0.05). RSS was higher in Group A as compared to Group M and
      Group P (P < 0.05). No significant difference in orientation score was observed
      in all the three groups before and after premedication (P > 0.05). DSST score
      (cognitive function) was better in Group M when compared to both Group A and
      Group P (P < 0.05). Conclusion: Oral melatonin (6 mg) when used as a premedicant
      is an effective alternative to alprazolam regarding providing better anxiolysis,
      lesser sedation along with maintenance of cognitive, and psychomotor function.

PMID- 30283172
TI  - Comparative Efficacy and Safety of Intravenous Clonidine and Tramadol for Control
      of Postspinal Anesthesia Shivering.
AB  - Background: Shivering is a common problem in patients undergoing surgery under
      spinal anesthesia. Aims: The aim of this study was to compare efficacy and safety
      of clonidine versus tramadol in postspinal anesthesia shivering. Settings and
      Design: This prospective, randomized, double-blind controlled clinical trial was
      conducted in a tertiary care setting. Materials and Methods: A total of 60
      American Society of Anesthesiologists physical status Class l and II adult
      patients (age 18-65 years) undergoing surgery under spinal anesthesia and
      developed shivering received either clonidine 1 MUg/kg or tramadol 1 mg/kg
      intravenously. The time required for cessation of shivering, control and
      recurrence rate of shivering, effect on hemodynamics and side effects were
      compared between two groups. Statistical Analysis: Unpaired t-test and Chi-square
      test were used for comparison of continuous variables and dichotomous data
      between two groups, respectively. P < 0.05 was considered as statistically
      significant. Results: Time for cessation of shivering was less in clonidine group
      than tramadol group (02.51 vs. 04.82 min; P < 0.001). Complete control of
      shivering was achieved in 80% of patients in clonidine group versus 70% in
      tramadol group. There was no significant difference for control (P = 0.5) and
      rate of recurrence of shivering between clonidine and tramadol group (06.7% vs.
      16.7%; P = 0.42). Pulse rate and systolic blood pressure were significantly lower
      in clonidine group at 5 and 15 min as compared with tramadol. Significantly more
      number of patients experienced nausea and dizziness (36.7% vs. 0%; P < 0.001 and
      20% vs. 0%; P = 0.01) with tramadol while bradycardia and hypotension were
      numerically more common in patients receiving clonidine (6.7% vs. 0% and 13.3%
      vs. 0%). Conclusion: Clonidine provides early relief from shivering than tramadol
      with fewer side effects in patients undergoing surgery under spinal anesthesia.

PMID- 30283173
TI  - A Study to Compare the Analgesic Efficacy of Dexmedetomidine and Fentanyl as
      Adjuvants to Levobupivacaine in Ultrasound-Guided Supraclavicular Brachial Plexus
      Block.
AB  - Background: Supraclavicular brachial plexus provides complete and reliable
      anesthesia for upper limb surgeries. Adjuvants are added to local anesthetists to
      improve various block characteristics. There are limited studies comparing the
      efficacy of dexmedetomidine and fentanyl as an adjuvant to levobupivacaine. Aims:
      The aim of the study was to evaluate and compare the effect of dexmedetomidine
      versus fentanyl as an adjuvant with levobupivacaine in ultrasound-guided
      supraclavicular brachial plexus block. Settings and Design: This study design was
      a prospective, randomized, double-blind controlled study. Subjects and Methods: A
      total of 120 patients in the age group of 30-55 years with physical status
      American Society of Anesthesiologists Classes I and II undergoing elective upper
      limb surgeries under ultrasound-guided supraclavicular brachial plexus block were
      randomly divided into three groups of forty each after taking informed consent
      and approval from Hospital Ethics Committee: Group A received 25 ml of 0.5%
      levobupivacaine with 5 ml normal saline (NS). Group B received 25 ml of 0.5%
      levobupivacaine with 1 MUg/kg dexmedetomidine diluted to the volume of 5 ml NS.
      Group C received 25 ml of 0.5% levobupivacaine with 1 MUg/kg fentanyl diluted to
      the volume of 5 ml NS. Onset and duration of sensory and motor block and duration
      of analgesia were noted and any side effects were observed. Statistical Analysis:
      The distribution of variables tested with Shapiro-Wilk test. Group comparison of
      values was made by Kruskal-Wallis test followed by Mann-Whitney test. Results:
      There was fastest onset time as well as longer duration of sensory and motor
      block in dexmedetomidine group, intermediate in fentanyl group as compared to
      levobupivacaine group. Conclusion: This study concludes that addition of
      dexmedetomidine to levobupivacaine for supraclavicular brachial plexus block
      shortens the onset time and prolongs the duration of sensory and motor blockade
      as compared to the addition of fentanyl.

PMID- 30283174
TI  - Efficacy of Combination of Esmolol and Diltiazem for Attenuating Hemodynamic
      Response to Laryngoscopy and Intubation: A Prospective Randomized Study.
AB  - Background: Laryngoscopy and tracheal intubation (LTI) are known to release
      catecholamines resulting in rise in heart rate (HR) and blood pressure. Various
      drugs have been studied till date to attenuate the sympathomimetic effects of
      laryngoscopy and intubation. Aims: The aim is to study the effect and safety of
      esmolol, diltiazem, and their combination on pressor response of laryngoscopy and
      intubation. Setting and Design: This prospective, randomized double-blind study
      was designed to assess the efficacy of the combination of esmolol and diltiazem
      and compare it with esmolol and diltiazem when used alone, for attenuating the
      pressor response to laryngoscopy and intubation. Materials and Methods: One
      hundred twenty-four adult patients of physical status American Society of
      Anesthesiologists Classes I and II posted for elective surgery under general
      anesthesia requiring endotracheal intubation were randomly allocated (using
      computer-generated random numbers) into four groups of 31 each, in a double-blind
      fashion, to receive the test drug, i.e., saline (control), diltiazem (0.2 mg/kg),
      esmolol (1.5 mg/kg), or a combination (diltiazem [0.1 mg/kg] and esmolol [0.75
      mg/kg]). The test drug was administered intravenously as a bolus after 1 min of
      injecting the muscle relaxant. LTI was performed after 2 min of the test drug.
      Hemodynamic data - HR, systolic blood pressure (SBP), diastolic blood pressure
      (DBP), and mean arterial pressure (MAP) - were recorded at 1 min intervals after
      induction, until laryngoscopy and intubation, and at 1, 2, 3, 4, 5, and 10 min
      thereafter. Statistical Analysis: Statistical analysis was performed using one
      way analysis of variance (ANOVA) for comparison among and between the groups. The
      Bonferroni's correction was applied when a significant difference was found
      between groups after applying ANOVA. Results were considered statistically
      significant at P <= 0.05. Results: In the control and diltiazem groups, a
      significant increase in HR (P <= 0.05) was observed after laryngoscopy. Esmolol
      and combination groups were associated with a significant fall in HR after
      administration of the test drug, and no significant rise was noted after
      laryngoscopy. HR was significantly less in the combination and esmolol groups as
      compared to the control till 5 min after LTI. As compared with the control, all
      the other groups were associated with a fall in SBP after the test dose, and this
      lasted for 5 min (P < 0.001) after laryngoscopy in the esmolol and combination
      groups and for 1 min (P < 0.001) in the diltiazem group. All groups were
      associated with a significant rise in DBP and MAP for 1-2 min after LTI (P <
      0.001), except the combination group in which no change was noted. DBP and MAP
      were significantly less in the combination group as compared to the control, from
      1 min after giving the test dose till 5 min (P < 0.001) after LTI. Conclusion:
      Although esmolol and combination groups were both effective in controlling the
      increase in HR and SBP, only the combination group was effective in controlling
      the rise in DBP and MAP after LTI. HR, SBP, DBP, and MAP were significantly less
      in the combination group as compared to the control till 5 min after LTI. We
      recommend a combination of esmolol and diltiazem in appropriate doses for
      effectively attenuating the rise in HR and blood pressure responses during LTI.

PMID- 30283175
TI  - Assessment of Relationship between Vitamin D Deficiency and Pain Severity in
      Patients with Low Back Pain: A Retrospective, Observational Study.
AB  - Background: Vitamin D is associated with musculoskeletal function in our body,
      and its deficiency is a common health problem all over the world. Low back pain
      (LBP) is an important health problem in terms of low quality of life, loss of
      work power, and cost of diagnosis and treatment approaches. Aims: The purpose of
      this study is to investigate the relationship between pain severity and Vitamin D
      deficiency in patients who applied to pain polyclinic with LBP. Settings and
      Design: This was a retrospective, observational study. Subjects and Methods: The
      files of patients aged between 18 and 70 years who applied to our hospital
      between January and February 2018 were examined retrospectively by a specialist.
      Serum 25-hydroxyvitamin D (25(OH)D) level, Visual Analogue Scale (VAS), age,
      education level, marital status, working status, and body mass index (BMI) values
      recorded in patient files were included in the study. The limit value of Vitamin
      D was accepted as 20 ng/mL. Patients were divided into two groups according to
      their levels of Vitamin D. Patients with serum 25(OH)D levels below 20 ng/mL were
      considered as the deficiency of Vitamin D (Group 1) and patients with 20 ng/mL
      and over 20 ng/mL values were considered as normal in terms of Vitamin D (Group
      2). Statistical Analysis Used: Descriptive statistical data were presented as
      mean, standard deviation, numbers, and percentage. There was no difference
      between the normally distributed group and the non-normally distributed group in
      terms of vitamin D levels. To compare the frequencies, the Chi-square test was
      used. To define the linear association between independent variables and Vitamin
      D level, Spearman's rho correlation coefficients were calculated. Results: The
      level of Vitamin D was measured in 98 patients aged 18-70 years who applied to
      our hospital's polyclinic due to LBP during the study period. The deficiency of
      vitamin was detected in 84 (85.7%) of the patients, while Vitamin D was found in
      14 (14.3%) as normal. Groups were similar in terms of age, gender, BMI,
      educational level, marital status and working status (p> 0.05); however, there
      was a statistically significant difference between the two groups in terms of VAS
      score and levels of Vitamin D (P < 0.001 and P < 0.001, respectively). While
      there was a negative correlation between D vitamin level and VAS score (r = 
      0.594, P < 0.001), there was no correlation between age, gender, BMI, education
      level, marital status, and working status (P > 0.05). Conclusions: The deficiency
      of Vitamin D is often asymptomatic, and also, it can cause bone and muscle pain.
      In our study, we determined that the severity of pain increased in patients with
      LBP as the deficiency of Vitamin D increased. For this reason, we recommend to be
      evaluated the level of Vitamin D in patients with LBP.

PMID- 30283176
TI  - Study of Wound Instillation Technique for Effective Postoperative Analgesia using
      Ropivacaine in Lumbar Spine Surgery.
AB  - Background: Instillation of local anaesthetics over incision site is a simple
      technique done as a part of multimodal analgesia targetting incisional pain for
      post-operative pain relief following lumbar laminectomy. Aim: To determine
      postoperative analgesic effect of ropivacaine in wound instillation for lumbar
      laminectomy. Study Design: Prospective, randomised, double blind study.
      Methodology: Forty patients scheduled for elective lumbar laminectomy under
      general anaesthesia were enrolled and randomly allocated into two groups namely
      Group R (n=20 receiving 20ml of 0.25% ropivacaine) and Group N (n=20 receiving
      20ml normal saline) as instillation over incision site. If the NRS exceeded '4'
      at any point of time, rescue analgesia with inj. Diclofenac 75 mg deep
      intramuscular was administered. Post- operative pain score, duration of analgesia
      and total rescue analgesic required in 24 h were compared between the groups.
      Results: The pain score was less in ropivacaine group as compared to normal
      saline group (p value 0.0001). Duration of analgesia in normal saline group (N)
      is 4.3+/- 1.03 and in ropivacaine group(R) is 12.15+/-1.49. Mean amount of rescue
      analgesic required in normal saline group was 191.25+/- 38.28mg and in
      ropivacaine group was 97.5+/- 35.26 mg. Conclusion: The patients who received
      ropivacaine wound instillation had better pain control, longer duration of
      analgesia and less analgesic requirement as compared to patients who received
      normal saline wound instillation.

PMID- 30283177
TI  - A Study Comparing Propofol Auto-coinduction and Standard Propofol Induction in
      Patients Undergoing General Anesthesia Without Midazolam Pretreatment: A
      Prospective Randomized Control Trial.
AB  - Background: Propofol has emerged as an induction agent of choice over the past
      two decades due to its quick, smooth induction and rapid recovery. The main
      concern for an anesthesiologist is the hemodynamic instability caused by the
      standard induction dose of propofol (2-3 mg/kg). Aim: We aim to study the
      efficacy of propofol auto-coinduction technique in comparison to the standard
      propofol induction technique in terms of the total induction dose requirement of
      propofol, the incidence of hemodynamic side effects and pain on injection, and
      the incidence of fentanyl-induced cough (FIC) in the absence of a synergistic
      agent like midazolam. Materials and Methods: This was a prospective, observer
      blinded, randomized controlled trial. The study was initiated after obtaining the
      institutional ethics committee approval and is registered in the Clinical Trials
      Registry India. Eighty American Society of Anesthesiology Physical Status I and
      II patients, of either sex, aged between 18 and 55 years, and scheduled for
      elective surgeries under general anesthesia were randomized into two equal
      groups. Patients allocated to Group I (auto-coinduction) received 20% of the
      calculated dose of injection propofol 2 mg/kg (i.e., 0.4 mg/kg) as the priming
      dose followed by injection fentanyl 1 MUg/kg after 1 min and the remaining
      propofol was administered in titrated doses till loss of verbal response after 2
      min. In Group II (control), patients received injection fentanyl 1 MUg/kg
      followed by single bolus dose of injection propofol up to 2 mg/kg till loss of
      verbal response. Midazolam was not used for premedication or induction.
      Intubation was carried out only after ensuring achievement of optimum depth of
      anesthesia using bispectral index scale. The total dose of propofol administrated
      for induction, occurrence of pain on injection, severity of cough after fentanyl
      administration, hemodynamic parameters, and apneic episodes were recorded.
      Statistical Analysis: All data were expressed as mean +/- 2 standard deviation.
      For statistical analysis, SPSS software version 16 (SPSS Inc., 2007, Chicago, IL,
      USA) was used. Results: The mean dose of injection propofol required for
      induction was significantly lower in Group I (67.0 +/- 17.9 mg) when compared
      with Group II (111.3 +/- 17.6 mg) (P < 0.01). The mean heart rate was
      significantly higher (P < 0.01) and the mean blood pressure was significantly
      lower in Group II (P < 0.01) when compared to Group I at 1 min postinduction,
      immediately after intubation, and 5 min after induction. The incidence of
      complications such as hypotension, pain on injection, and FIC was higher in Group
      II (50%) as compared to Group I (18%). Conclusion: In our study, we found that
      the induction dose requirement of propofol was significantly lower in the auto
      coinduction group when compared to the conventional induction group. The auto
      coinduction technique offered a stable hemodynamic profile, reduced pain on
      injection, and less incidence of FIC as compared to the conventional propofol
      induction technique.

PMID- 30283178
TI  - Comparison of Blind Endotracheal Aspiration and Bronchoscopic Brush Biopsy
      Sampling Methods for Bacteriological Diagnosis of Ventilator-Associated Pneumonia
      in Intensive Care Unit.
AB  - Background: The diagnosis of ventilator-associated pneumonia (VAP) is a challenge
      because the clinical signs and symptoms lack both sensitivity and specificity.
      Further confirmation of the diagnosis of VAP can be done by other diagnostic
      procedures such as bronchoscopic and blind endotracheal aspiration, but the
      selection of either diagnostic procedure is debatable. Aims: The aim is to study
      and compare the role of bronchoscopic protected specimen brush biopsy (PSBB) and
      blind endotracheal aspiration for diagnosis of VAP. Settings and Design: This
      prospective comparative study was conducted in multidisciplinary Intensive Care
      Unit of a tertiary care hospital. Materials and Methods: Thirty patients
      clinically diagnosed to have VAP were further evaluated by bronchoscopic and
      blind endotracheal aspiration. The P value of PSBB and blind aspiration
      techniques was calculated, taking clinical pulmonary infection score of >=6 as
      reference standard. Statistical Analysis Used: Statistical analysis was done
      using Chi-square and t-test. Results and Conclusions: Our study shows that for
      the diagnosis of VAP, PSBB and blind aspiration had Chi-square value of 0.83 with
      degree of freedom 1 which showed P = 0.3623 which is not significant. t-test
      value is 0.402 with degree of freedom 1 and P = 0.7567 which is still not
      significant. There was a good microbiologic concordance among bronchoscopic and
      nonbronchoscopic distal airway sampling techniques. Blind endotracheal aspiration
      is a comparable technique for bacteriological diagnosis of VAP.

PMID- 30283179
TI  - Efficacy of Dexmedetomidine Added to Ropivacaine Infilteration on Postoperative
      Pain following Spine Surgeries: A Randomized Controlled study.
AB  - Context: With modern lifestyle, there has been a steep increase in the number of
      low back pain patients in clinical practice. Lumbar microdiscectomy is one of the
      most common surgeries performed for this problem. Postoperative pain management
      is extremely important aspect of such advanced surgical technique among which
      wound infiltration is an efficient method. Aims: The aim of the study was to
      compare the efficacy of dexmedetomidine added to ropivacaine verses plain
      ropivacaine following wound infiltration in terms of pain scores, requirement of
      rescue analgesia, and related adverse effects. Settings and Design: Randomized,
      prospective, controlled, double-blind study over a period of 1 year in a tertiary
      care hospital. Materials and Methods: Sixty patients scheduled for lumbar
      discectomy were randomly allocated into two groups. Group A received wound
      infiltration with 30 ml 0.2% ropivacaine before wound closure and Group B
      received wound infiltration with 1ug/kg dexmedetomidine added to 30 ml of 0.2%
      ropivacaine before wound closure. Data retrieved were demographic data, visual
      analog scores, postoperative pain scores, rescue analgesia by patient controlled
      analgesia pump, recovery profile, and adverse effects. Statistical Analysis Used:
      Data were analyzed using statistical software SPSS version 22. Mann-Whitney test,
      Kruskal-Wallis test, and Chi-square test were used as applicable. Results:
      Demographic data were comparable between the groups. Requirement of rescue
      analgesia was significantly less in Group B where combination of dexmedetomidine
      and ropivacaine was given. Conclusions: Dexmedetomidine provided effective
      postoperative analgesia and reduced fentanyl consumption when administered in
      wound infiltration with ropivacaine.

PMID- 30283180
TI  - The Effects of the Quincke Spinal Needle Bevel Insertion on Postdural Puncture
      Headache and Hemodynamics in Obstetric Patients.
AB  - Aim: Spinal anesthesia is a widely used procedure in modern anesthesia. Although
      it is a reliable and frequently used anesthetic procedure, it involves
      complications, including postdural puncture headache caused by arachnoid
      punctured, which significantly affects postoperative well-being. In this study,
      we aimed to observe headache frequency with 26-G Quincke spinal needle in either
      transverse or sagittal planes. Materials and Methods: One hundred patients with
      American Society of Anesthesiologists status classes I and II who were scheduled
      for elective cesarean delivery with no contraindications for performing spinal
      anesthesia were randomly divided into two groups: Group I (transverse n = 50) and
      Group II (sagittal n = 50). Spinal anesthesia was performed with a 26-G Quincke
      needle, using 1.5-2.0 ml 0.75% hyperbaric bupivacaine. The anesthesiologists'
      experience, number of attempts for spinal anesthesia, volume of fluid
      administered preoperatively and intraoperatively, intervertebral space where
      spinal anesthesia was administered, and patient movements during the attempts
      were recorded. Mean arterial pressure and peak heart rates were recorded for 60
      min intraoperatively and postoperatively. Headache and back pain complications
      were observed for 1 week postoperatively. Chi-square tests and statistical
      comparisons of the rates (statistical significance, P < 0.05) were used for
      assessments. Results and Conclusions: No significant differences were observed
      with respect to age, height, weight, headache, or incidence of back pain. No
      significant differences were observed for the number of spinal attempts,
      intervertebral space where spinal anesthesia was administered, experience of the
      anesthesiologists, patient movements during the attempts, volumes of fluid
      administered preoperatively and intraoperatively, or low back pain incidence.
      Significant reductions in mean arterial pressure were observed between groups
      after 10, 15, 30, 40, and 50 min. No significant differences were observed in
      headache or back pain frequency with 26-G Quincke spinal needle in either
      transverse or sagittal planes. Hypotension was frequently observed in the
      transverse group.

PMID- 30283181
TI  - A Study to Assess the Efficacy of Different Doses of Propofol for Tracheal
      Intubation: A Randomized Clinical Trial.
AB  - Background: Tracheal intubation is usually facilitated by using a muscle relaxant
      to supplement drugs given for the induction of general anesthesia.
      Nondepolarizing muscle relaxants are also associated with the few disadvantages.
      Endotracheal intubation under volatile anesthetics without the use of muscle
      relaxants is possible, but it has disadvantages. Time available for intubation is
      much less when compared to the use of muscle relaxants. Considering the
      disadvantages of muscle relaxants and volatile agents in mind, there is a need
      for endotracheal intubation without muscle relaxants. Objective: The objective of
      the study is to assess the efficacy of different doses of propofol for tracheal
      intubation - a randomized clinical trial. Materials and Methods: A randomized
      study was conducted on 80 patients, comprising of 40 patients each. Patients of
      either sex were randomly allocated into Group P1 and Group P2 by computer
      generated random numbers where Group P1 received 2 mg/kg propofol +3 MUg/kg
      fentanyl and Group P2 received 4 mg/kg propofol +3 MUg/kg fentanyl. SpO2, heart
      rate, blood pressure (BP)- systolic BP, diastolic BP, and mean arterial pressure
      were recorded at 1 and 3 min after administration of study drugs were recorded.
      Intubating conditions were assessed modified Helbo-Hansen scoring system.
      Results: The success rate of endotracheal intubation was 62.5% and 95% in
      propofol 2 mg/kg + fentanyl 3 MUg/kg and propofol 4 mg/kg + Fentanyl 3 MUg/kg,
      respectively. The total incidence of hypotension was 40% and 83% in propofol 2
      mg/kg + Fentanyl 3 MUg/kg and propofol 4 mg/kg + Fentanyl 3 MUg/kg, respectively.
      The incidence of hypersensitivity was noted only in propofol 4 mg/kg + Fentanyl 3
      MUg/kg group and was 2.5%. Conclusion: We conclude that endotracheal intubation
      is possible in premedicated adult American Society of Anesthesiologists by Grade
      I patients with receiving 3 MUg/kg Fentanyl + 2 mg/kg or 4 mg/kg propofol for
      induction without muscle relaxants, and the intubating conditions are acceptable.
      We found that propofol 4 mg/kg + Fentanyl 3 MUg/kg is the optimal dose required
      for intubation without the use of muscle relaxants.

PMID- 30283182
TI  - Comparative Study between Magnesium Sulfate and Lidocaine for Controlled
      Hypotension during Functional Endoscopic Sinus Surgery: A Randomized Controlled
      Study.
AB  - Background: Intraoperative bleeding impairs surgical field visibility during
      functional endoscopic sinus surgery (FESS); several methods have been used to
      decrease blood loss and improve surgical field, one of them is usage of
      hypotensive anesthetic agents. Aim: We intended to compare magnesium sulfate with
      lidocaine, regarding their efficiency in inducing controlled hypotension and
      providing a better surgical field exposure during FESS and the influence of their
      usage on extubation time. Settings and Design: This study design was a
      prospective randomized controlled double-blinded clinical study. Patients and
      Methods: Eighty adult patients with patients' physical status ASA Classes I and
      II, aged 20-50 years scheduled for FESS were randomly divided into two study
      groups; each group contains 40 patients: Group L received lidocaine 2 mg/kg/h
      with maximum of 200 mg/h starting at induction of anesthesia and continuing until
      the end of surgery and Group M received an iv bolus of magnesium sulfate 50mg/kg
      in a total of 100ml saline over 10 min followed by infusion of 15mg/kg/h until
      the end of surgery; patients were observed for the quality of the surgical field,
      blood loss, and extubation time. Statistical Analysis Used: Student's t-test or
      Mann-Whitney's U, Chi-square, or Fisher's exact tests were used. Results: Group L
      showed a significant decrease in blood loss (P = 0.01), better surgical field
      clarity (P = 0.002), and shorter extubation time (P = 0.001) than Group M, but
      there was no statistically significant difference between the two study groups as
      regards hemodynamics. Conclusion: We concluded that both magnesium sulfate and
      lidocaine successfully induced controlled hypotension in patients undergoing
      FEES, but lidocaine provided better surgical field clarity and shorter extubation
      time.

PMID- 30283183
TI  - Evaluation of the Metabolic Profile of Ringer Lactate versus Ringer Acetate in
      Nondiabetic Patients Undergoing Major Surgeries.
AB  - Background: Stress-induced neuroendocrine and metabolic changes lead to
      intraoperative hyperglycemia which is related to surgery and the type of
      intravenous fluids used. Aims: The primary objective was to assess the incidence
      of hyperglycemia with use of lactate versus acetate-based intravenous fluids in
      nondiabetics undergoing major surgeries. Incidence of lactatemia and metabolic
      acidosis were also assessed. Settings and Design: Prospective parallel group
      observational study conducted in a tertiary care institute. Subjects and Methods:
      A total of 208 nondiabetic patients undergoing major head and neck free flap or
      abdominal surgeries were included in the study. Group A received Ringer lactate,
      and Group B received Ringer acetate as intraoperative maintenance fluid.
      Intraoperative blood sugar, pH, and lactate levels were monitored. Statistical
      Tests Used: Chi-square test and independent "t" test were used for analysis.
      Results: Intraoperative hyperglycemia was more frequent in Group A than B (17.3
      vs. 18.4%). Group B patients undergoing gastrointestinal (GI) surgeries showed
      higher blood glucose at 2, 4, 6, and 8 h when compared to flap surgeries. In
      Group A, significantly higher blood sugar values were noted at 2 and 8 h in those
      undergoing GI surgeries. Group B patients undergoing GI surgeries had
      significantly higher lactate levels at 6 and 8 h. Group B patients had
      significant acidosis when surgeries lasted >6 h. Conclusion: Nondiabetic patients
      undergoing major abdominal surgeries who received acetate-based fluids had
      relatively higher intraoperative blood sugar levels as compared to those
      receiving lactated solutions, but the incidence of hyperglycemia was comparable.
      When the duration of surgery exceeded 6 h, acetate-based solutions resulted in
      significantly higher lactate levels with progressive metabolic acidosis.

PMID- 30283184
TI  - The Efficacy of Intravenous Magnesium Sulfate versus Intravenous Paracetamol on
      Children Posttonsillectomy Pain and Analgesic Requirement: A Randomized
      Controlled Study.
AB  - Background: One of the most common complications of tonsillectomy is pain, which
      leading to delayed recovery and later hospital discharge. Aims: We intended to
      compare the efficacy of magnesium sulfate versus paracetamol on the
      posttonsillectomy pain and analgesic requirement. Settings and Design: This study
      design was a prospective randomized controlled double-blinded clinical study.
      Patients and Methods: A total of 60 children with the American Society of
      Anesthesiologists physical status classes I and II, aged 3-12 years, scheduled
      for tonsillectomy were randomly divided into two groups each group contains 30
      patients: (Group M): received an initial loading dose of magnesium sulfate 30
      mg/kg over 15 min started with induction followed by continuous infusion of 10
      mg/kg/h for 1 h regardless of the operation time and (Group P): received
      paracetamol infusion 10 mg/kg started with induction and continued for 1 h.
      Postoperatively, a blinded postanesthesia care unit (PACU) nurse observed the
      quality of analgesia using the face, legs, activity, cry, and consolability pain
      scores, bleeding, and sedation. Statistical Analysis Used: Student's t-test and
      Chi-square test were used for analysis. Results: Regarding postoperative pain,
      there was a statistically significant difference between the two groups at the
      time of admission in PACU (P = 0.025) as children who experienced pain already
      had taken rescue analgesic to alleviate pain. There was a statistically
      significant difference between the two groups regarding the need for analgesics
      (P = 0.038). There was no statistically significant difference regarding bleeding
      and sedation scores between the two study groups. Conclusions: Magnesium sulfate
      provided better postoperative analgesia and reduced need for analgesics after
      tonsillectomy compared to paracetamol, and regarding the incidence of bleeding
      and the degree of sedation the outcome in both groups was readily comparable.

PMID- 30283185
TI  - Use of Butorphanol, Fentanyl, and Ketamine as Co-Induction Agents with Propofol
      for Laryngeal Mask Airway Insertion: A Comparative Study.
AB  - Background: Management of airway is of great importance in the practice of
      anesthesia. Supraglottic airway devices, such as laryngeal mask airway (LMA),
      have greatly revolutionized the management of airway both in terms of ease and
      degree of invasiveness. Propofol, by its inherent property of decreasing airway
      reflexes, is used to aid in LMA insertion. In this study, we have evaluated the
      LMA insertion conditions and hemodynamic stability, comparing butorphanol,
      fentanyl, and ketamine as co-induction agents with propofol. Materials and
      Methods: A total of 90 female patients planned to undergo minor gynecological
      procedures were randomly allocated to one of the three study groups. Patients in
      Group B received butorphanol 20 MUg/kg, patients in Group F received fentanyl 1
      MUg/kg, and patients in Group K received ketamine 0.5 mg/kg intravenously before
      injection of propofol 2.5 mg/kg. LMA insertion conditions were graded according
      to the modified scheme of Lund and Stovner, and hemodynamic parameters were
      recorded. The results were analyzed statistically. Results: The patients in all
      the three groups were comparable in their demographic characteristics. The mean
      total dose of propofol used in Group B was 136.50 mg (standard deviation [SD]
      27.70), in Group F was 139.33 mg (SD 28.52), and in Group K was 156.33 mg (SD
      38.64). Excellent insertion conditions were observed in 25 (83.3%) patients in
      Group B, 25 (83.3%) patients in Group F, and 15 (50%) patients in Group K. Group
      B and Group K showed a more stable hemodynamic profile than Group F. Conclusion:
      It is concluded that the use of butorphanol as a co-induction agent with propofol
      provides excellent insertion conditions and stable hemodynamics compared to
      fentanyl or ketamine.

PMID- 30283186
TI  - Role of Lignocaine Nebulization as an Adjunct to Airway Blocks for Awake Fiber
      Optic Intubation: A Comparative Study.
AB  - Context: Airway management is a crucial skill and area of concern for the
      anesthesiologist. Awake fiber-optic intubation (AFOI) remains the gold standard
      in managing difficult airway. Anaesthetizing the airway along with psychological
      assurance is the mainstay for Preparation of AFOI. Different topical and regional
      techniques have been developed to subdue reflexes and facilitate AFOI. Aim: This
      randomized controlled study was performed to evaluate the effectiveness of using
      lignocaine nebulization in addition to specific airway blocks for AFOI.
      Methodology: This was a comparative study conducted in 60 patients with difficult
      airway (LEMON score >2) and randomly allocated into two groups of 30 each. Group
      LB and Group NB received nebulization of 2% lignocaine 4 mL and 0.9% normal
      saline 4 mL, respectively. Both groups were then given airway blocks as bilateral
      superior laryngeal (2% lignocaine 1-2 mL each) and transtracheal (2% lignocaine 4
      mL) block. Two puffs of 10% lignocaine to nose and postnasal space on each side
      were given in both groups. Fiber-optic bronchoscopy (FOB)-guided tracheal
      intubation was Performed. Vital parameters, side effects, bronchoscopy-guided
      intubation time and other parameters as intubation grading scale, patient comfort
      score, satisfaction score were recorded. Chi-square test and unpaired t-test were
      used for statistical analysis. Results: Statistically, no significant differences
      were found in hemodynamic parameters, demographics, intubation time, and
      intubation grading scale in both groups. However, overall patient comfort and
      satisfaction score was better in Group LB. Conclusion: Upper airway blocks
      provide adequate anesthesia for awake FOB, but when lignocaine nebulization is
      added to these blocks, it improves the quality of anesthesia and patient
      satisfaction.

PMID- 30283187
TI  - Quadratus Lumborum Block versus Transversus Abdominis Plane Block in Patients
      Undergoing Total Abdominal Hysterectomy: A Randomized Prospective Controlled
      Trial.
AB  - Background: Abdominal hysterectomy is associated with sever postoperative pain.
      Quadratus lumborum (QL) block is a regional analgesic technique which has an
      evolving role in postoperative analgesia. Aims: we aimed to compare ultrasound
      guided bilateral transverse abdominis plane (TAP) block versus bilateral QL block
      in patients undergoing total abdominal hysterectomy. Settings and Design: This is
      a prospective randomized controlled double blinded study. Patients and Methods:
      Sixty adult female patients (ASA I-II), scheduled for total abdominal
      hysterectomy were randomized into two equal groups (TAP group and QL group). Each
      patient received general anesthesia plus bilateral TAP block or bilateral QL
      block. We recorded postoperative total dose of morphine used / 24 hours, Visual
      Analuge Scales (VAS) for pain (at 30 min, 2, 4, 6, 12, and 24 hours
      postoperative), duration of postoperative analgesia, total dose of fentanyl use
      intraoperative, number of patients needed rescue analgesia and any side effects.
      Statistical Analysis: Independent sample T test and Chi-Square (X2) test were
      used as appropriate. Results: Patients in QL group consumed significantly less
      fentanyl and morphine than patients in TAP group, VAS for pain was significant
      higher in TAP group than in QL group at all times, the duration of postoperative
      analgesia was shorter in TAP group than in QL group, the number of patients
      requested analgesia was significantly higher in TAP group than in QL group.
      Conclusions: Bilateral QL block provided better intraoperative and postoperative
      analgesia with less opioids consumption compared with bilateral TAP block, in
      patients undergoing total abdominal hysterectomy.

PMID- 30283188
TI  - Intranasal Fentanyl, Midazolam and Dexmedetomidine as Premedication in Pediatric
      Patients.
AB  - Background: Surgery is a very stressful experience for patients. Children are the
      most susceptible to fear, anxiety, and stress due to their limited cognitive
      capabilities and dependency. In children, pharmacologic agents are frequently
      used as premedication to relieve the fear of surgery, to make child-parental
      separation easy, and to carry out a smooth induction of anesthesia. We conducted
      this study to compare the efficacy of intranasal fentanyl, midazolam, and
      dexmedetomidine as premedication in pediatric patients. Materials and Methods:
      The present study was conducted prospectively on 75 patients in the age group of
      2-6 years of either sex of the American Society of Anesthesiologists physical
      Class I or II admitted in Guru Nanak Dev Hospital, attached to Government Medical
      College Amritsar, scheduled to undergo surgery under general anesthesia. The
      patients were divided into three groups of 25 each. Group F received intranasal
      fentanyl 1.5 MUg/kg body weight, Group M received intranasal midazolam 0.3 mg/kg
      body weight, and Group D received intranasal dexmedetomidine 1 MUg/kg body weight
      as nasal drops 50 min before surgery. Results: Children who received intranasal
      fentanyl and intranasal midazolam had early onset of anxiolysis and sedation as
      compared to dexmedetomidine. In child-parent separation, quality of induction was
      better with fentanyl and dexmedetomidine as compared to midazolam. Intravenous
      cannulation score was best achieved with fentanyl as premedicant. Postoperative
      sedation was better with dexmedetomidine as compared to fentanyl and midazolam.
      Conclusion: Onset of action of fentanyl and midazolam is early as compared to
      that of dexmedetomidine. However, fentanyl provided better conditions for
      induction and emergence than midazolam. With dexmedetomidine onset of action was
      delayed and duration of action was prolonged which helped child to remain calm
      and sedated even after the surgery.

PMID- 30283189
TI  - Efficiency and Efficacy of Two Techniques of Preoxygenation during Modified Rapid
      Sequence Intubation.
AB  - Background: Apneic mass movement of oxygen by applying continuous positive airway
      pressure (CPAP) is possible only when the airway is kept patent which helps to
      reduce the rate of desaturation. Aims: The aim of this study was to check the
      efficiency of preoxygenation and apneic oxygenation by assessing the drop in
      partial pressure of arterial oxygen (PaO2) during apnea with and without keeping
      an oropharyngeal airway to maintain the patency of airway. Settings and Design:
      This prospective observational study was conducted at a tertiary care center.
      Materials and Methods: Sixty patients undergoing robotic and laparoscopic
      assisted surgeries requiring modified rapid sequence intubation were recruited
      for the study. In Group A, CPAP was not applied during preoxygenation and
      oropharyngeal airway was not used, but oxygen was administered at 5 L/min during
      the apnea. In Group B, CPAP of 5 cmH2O was maintained during preoxygenation and
      after induction an oropharyngeal airway was inserted. Patients in both the groups
      were induced and paralyzed following standardized anesthesia protocol.
      Statistical Analysis Used: Chi-square test, independent t-test, and ANCOVA were
      used as applicable. Results: Group B showed significantly higher mean PaO2 levels
      after preoxygenation (525.3 +/- 42.5 vs. 500.8 +/- 51) and at 90 s of apnea
      (494.8 +/- 42.6 vs. 368.6 +/- 98.4) as compared to Group A. The fall in PaO2 was
      significantly lower in Group B. The rise in partial pressure of arterial carbon
      dioxide was comparable in both groups. Conclusion: Preoxygenation with CPAP of 5
      cmH2O followed by apneic oxygenation with CPAP keeping the airway patent with an
      oropharyngeal airway results in significantly higher PaO2 after preoxygenation
      and slower reduction in PaO2 during apnea.

PMID- 30283190
TI  - Anesthetic Management in Corpus Callosum Agenesis.
AB  - Corpus callosum agenesis develops when the band which connects the two
      hemispheres of the brain does not occur in utero. It is associated with prenatal
      infections, genetic factors, toxic exposures, metabolic disorders, and chromosome
      errors. Mostly seen clinical features are macrocephaly, microcephaly, seizures,
      motor retardation, hypotonia, eye anomalies, and facial dysmorphisms. Here, we
      report a case of corpus callosum agenesis syndrome undergoing upper endoscopy
      under deep sedation with dexmedetomidine. The main anesthetic concerns are
      difficulty in airway, respiratory problems, gastric reflux, and interaction of
      the seizures therapy with general anesthetics.

PMID- 30283191
TI  - Ultrasound-Guided Taylor's Approach in Ankylosing Spondylitis.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory disease of the spine which
      leads to ossification and formation of a classical bamboo spine. This poses a
      challenge to the anesthetist both in terms of administering general and regional
      anesthesia due to the limited mobility of the spine. With the advent of
      ultrasound as an aid in regional anesthesia, it has been relatively easy to
      perform a central neuraxial blockade in such patients though the skill requires
      some degree of expertise. Here, we have described the use of ultrasound as a
      guide for administering regional anesthesia to a patient with AS after initially
      attempting a blind approach which had failed due to difficult anatomy.

PMID- 30283192
TI  - Unilateral Acute Respiratory Distress Syndrome with Contralateral Pulmonary
      Artery Agenesis: A Rare Scenario.
AB  - Unilateral pulmonary artery agenesis (UPAA) is a rare condition where the patient
      may remain asymptomatic for a long period till adulthood. Presentation may be in
      the form of dyspnea, cough, hemoptysis, decreased exercise tolerance, and
      recurrent respiratory tract infections. Ventilation-perfusion mismatch and
      excessive blood flow to the normal lung may eventually lead to unilateral acute
      respiratory distress syndrome (ARDS). We present a case of a 40-year-old
      gentleman with nonresolving pneumonia who was diagnosed to have unilateral ARDS
      due to UPAA. Even though ARDS involves bilateral lung, unilateral ARDS which does
      not show resolution with lung protective strategies should always raise the
      suspicion of a rare disease like UPAA among clinicians. To date, there is no
      specific prescribed treatment for UPAA.

PMID- 30283193
TI  - Retraction: A Comparative Study of Dexmedetomidine and Diltiazem for Attenuating
      Pressor Responses to Laryngoscopy and Endotracheal Intubation: A Double-blind,
      Randomized Study.
AB  - [This retracts the article on p. 921 in vol. 11, PMID: 29284850.].

PMID- 30283194
TI  - Influence of oat components on lipid digestion using an in vitro model: Impact of
      viscosity and depletion flocculation mechanism.
AB  - Depletion flocculation is a well-known instability mechanism that can occur in
      oil-in-water emulsions when the concentration of non-adsorbed polysaccharide
      exceeds a certain level. This critical flocculation concentration depends on the
      molecular characteristics of the polysaccharide molecules, such as their
      molecular weight and hydrodynamic radius. In this study, a range of analytical
      methods (dynamic shear rheology, optical microscopy, and static light-scattering)
      were used to investigate the interaction between lipid droplets and
      polysaccharides (guar gum and beta-glucans) of varying weight-average molecular
      weight and hydrodynamic radius, and concentration. The aim of this work was to
      see if the health benefits of soluble fibers like beta-glucans could be explained
      by their influence on the structure and digestibility of lipid emulsions. The
      apparent viscosity of the emulsions increased with increasing polysaccharide
      concentration, molecular weight, and hydrodynamic radius. Droplet flocculation
      was observed in the emulsions only at certain polysaccharide concentrations,
      which was attributed to a depletion effect. In addition, the water-soluble
      components in oat flakes, flour, and bran were extracted using aqueous solutions,
      to examine their impact on emulsion stability and properties. Then, the rate and
      extent of lipolysis of a sunflower oil-in-water emulsion in the presence of these
      oat extracts were monitored using the pH-stat method. However, the inhibition of
      lipolysis was not linearly related to the viscosity of the oat solutions. The
      water-soluble extracts of beta-glucan collected from oat flakes had a significant
      inhibitory effect on lipolysis. The results of this study increase our
      understanding of the possible mechanisms influencing the impact of oat
      constituents on lipid digestion. This work also highlights the importance of
      considering the molecular properties of polysaccharides, and not just their
      impact on solution viscosity.

PMID- 30283195
TI  - SHIFT: speedy histopathological-to-immunofluorescent translation of whole slide
      images using conditional generative adversarial networks.
AB  - Multiplexed imaging such as multicolor immunofluorescence staining, multiplexed
      immunohistochemistry (mIHC) or cyclic immunofluorescence (cycIF) enables deep
      assessment of cellular complexity in situ and, in conjunction with standard
      histology stains like hematoxylin and eosin (H&E), can help to unravel the
      complex molecular relationships and spatial interdependencies that undergird
      disease states. However, these multiplexed imaging methods are costly and can
      degrade both tissue quality and antigenicity with each successive cycle of
      staining. In addition, computationally intensive image processing such as image
      registration across multiple channels is required. We have developed a novel
      method, speedy histopathological-to-immunofluorescent translation (SHIFT) of
      whole slide images (WSIs) using conditional generative adversarial networks
      (cGANs). This approach is rooted in the assumption that specific patterns
      captured in IF images by stains like DAPI, pan-cytokeratin (panCK), or alpha
      smooth muscle actin ( alpha-SMA) are encoded in H&E images, such that a SHIFT
      model can learn useful feature representations or architectural patterns in the
      H&E stain that help generate relevant IF stain patterns. We demonstrate that the
      proposed method is capable of generating realistic tumor marker IF WSIs
      conditioned on corresponding H&E-stained WSIs with up to 94.5% accuracy in a
      matter of seconds. Thus, this method has the potential to not only improve our
      understanding of the mapping of histological and morphological profiles into
      protein expression profiles, but also greatly increase the e ciency of diagnostic
      and prognostic decision-making.

PMID- 30283196
TI  - Benign Neoplasm of Kidney: Angiomyolipoma.
AB  - Angiomyolipoma is one of the renal benign neoplasms. The most of the
      angiomyolipomas are asymptomatic and found incidentally with ultrasound. They are
      more prevalent in patients with tuberous sclerosis. It is very important to make
      differential diagnosis from other renal neoplasm such as renal cell carcinoma.
      Growth rate is higher among pregnant women suggest that the hormones may play a
      role in the stimulation of angiomyolipoma. The most common serious presentation
      is rupture and hemorrhage, and sometimes it can lead to shock. Adequate
      diagnosis, treatment, and follow-up are very important in the face of renal
      angiomyolipoma.

PMID- 30283197
TI  - Chemical Items Used for Preparing Tissue-Mimicking Material of Wall-Less Flow
      Phantom for Doppler Ultrasound Imaging.
AB  - The wall-less flow phantoms with recognized acoustic features (attenuation and
      speed of sound), interior properties, and dimensions of tissue were prepared,
      calibrated, and characterized of Doppler ultrasound scanning demands tissue
      mimicking materials (TMMs). TMM phantoms are commercially available and ready
      made for medical ultrasound applications. Furthermore, the commercial TMM
      phantoms are proper for ultrasound purpose or estimation of diagnostic imaging
      techniques according to the chemical materials used for its preparation. However,
      preparing a desirable TMM for wall-less flow phantom using a specific chemical
      material according to the specific applications is required for different flow.
      In this review, TMM and wall-less flow phantoms prepared using different chemical
      materials and methods were described. The chemical materials used in Doppler
      ultrasound TMM and wall-less flow phantoms fabricated over the previous decades
      were of high interest in this review.

PMID- 30283198
TI  - The Most Appropriate Time Delay after Microbubble Contrast Agent Intravenous
      Injection to Maximize Liver Metastasis Conspicuity on Contrast-Enhanced
      Ultrasound.
AB  - Purpose: To identify the most appropriate time delay after microbubble contrast
      agent injection to maximize liver metastasis conspicuity on contrast-enhanced
      ultrasound (CEUS). Methods: Twenty-five consecutive patients (12 male and 13
      female; age: 50 +/- 13 years) with a known primary tumor and evidence of liver
      metastases on unenhanced ultrasound (US) underwent CEUS. CEUS consisted of
      continuous liver parenchyma scanning during arterial (15-35 s after microbubble
      injection), portal venous (40-120 s), and late phase (from 120 s up to
      microbubble disappearance). Subjective conspicuity index (ranging from 1 to 5)
      and objective conspicuity index (Ilesion-Iliver/Iliver, I = signal intensity)
      were calculated on reference frames selected on arterial phase and every 20 s on
      portal venous and late phase. Results: A total number of 40 liver metastases were
      identified after microbubble injection. The highest liver metastasis conspicuity
      was observed on early portal venous phase (40-60 s after microbubble injection)
      both on visual (mean subjective conspicuity index +/- standard deviation [SD] =
      4.36 +/- 0.75, reader 1; 4.25 +/- 0.65, reader 2) and quantitative analysis (mean
      objective conspicuity index +/- SD = -0.99 +/- 0.001). Conclusion: The early
      portal venous phase (40-60 s after microbubble injection) provides the best liver
      metastases' conspicuity after microbubble contrast agent injection.

PMID- 30283199
TI  - A New Scatter Particle and Mixture Fluid for Preparing Blood Mimicking Fluid for
      Wall-Less Flow Phantom.
AB  - Background: To examine the blood flow and detection of the issues related to it
      by medical ultrasound, it is extremely important to have suitable blood mimicking
      fluid (BMF) to be used in vitro and to have a movable or portable Doppler flow
      phantom to use it as a standardizing tool. As known, the main drawbacks of the
      currently commercial BMF used in the research studies are high in cost and the
      long time needed for preparation, which is at least 5-7 h. Moreover, there are
      only two common scatter particles using in BMF as suspension materials such as
      nylon (Orgasol) and polystyrene. Thus, we need to prepare BMF with both a new
      mixture fluid and new scatter particle to be as a reflecting factor of ultrasonic
      waves, for evaluating the speed of sound of the blood flow in the same method
      like in the research study of ultrasound with relatively low-cost and less
      consuming time of preparation. However, both the acoustical and physical features
      of the Doppler flow phantom components (BMF and tissue mimicking material) must
      correspond the features of the human tissues to make the examination
      significance. In addition, the BMF must also represent the hemodynamic features
      of real human blood. Methods: In this experiment, a new adequate ternary mixture
      liquid for preparation of BMF applied and suspended with a new scatter particle
      material, this scatter particle material called poly (4-methylstyrene), it used
      to be adequate with the mixture density and for saving neutrally buoyant. This
      BMF was prepared for use in the test objects or Doppler flow phantom. The poly (4
      methylstyrene) particles were applied for suspension in a mixture liquid or fluid
      based on three items, which were distilled water, propylene glycol (PG), and
      polyethylene glycol (PEG) (200 Mw). The diameter of poly (4-methylstyrene)
      particles is 3-8 MUm, which determined by specific sieve in a unit of MUm, and
      the density is 1.040 g/ml. Results: Speed of sound, viscosity, density,
      Backscatter power and attenuation features of mixture fluid or liquid which used
      for preparing a BMF were measured, discussed, and agreed with draft International
      Electrotechnical Commission values. Conclusions: There are three various types of
      ternary items of mixture fluid (water, PG, and PEG [200 Mw]), and a new type of
      scatter particle material poly (4-methylstyrene) was utilized for preparing the
      BMF. The scatter particles and mixture fluid prepared and measured at a
      temperature that simulates the body temperature 37 degrees C. Moreover, one of
      the advantages of this new blood that is being cheaper than the commercially
      available BMF products because the PG and the polyethylene glycol (200 Mw) are
      much cheaper and more available than glycerol and the Dextran that used usually.
      In addition, new BMF needs less time for preparation compared to the commercial
      one.

PMID- 30283200
TI  - A Single Static Breast Model Education of Ultrasound Skill in Final Year Medical
      Students of Burapha University.
AB  - Background: Ultrasound (US) is widely used among physicians. There has been no
      standardized curriculum in US for undergraduate medical students. This study
      aimed to assess the US image acquisition skill of final year medical students
      after adding 2 weeks dedicated radiology rotation. Methods: At our institution,
      there are two hospital affiliations. Two-week radiology rotation was added for
      the final-year students of one affiliation. These students had a chance to do the
      US in real-life clinical settings proctored by radiologists. At the end of the
      academic year, US image acquisition skill was assessed by objective structured
      clinical examination (OSCE) in students from both affiliations. Results: From 48
      final-year medical students, 28 students finished the 2 week radiology rotation.
      OSCE mean score of the students who received radiology rotation was significantly
      higher than other groups with a score of 65.5 compared to 53.3, respectively (P =
      0.006). The student background characteristics had no relationship with the OSCE
      score (P = 0.565). Conclusion: Results showed that exposure through a dedicated
      radiology rotation in only 2 weeks is helpful to improve the US skill of the
      medical students regardless of their background performances. Exposure to live
      patients is essential for students' experiences. OSCE can be used as a
      standardized assessment tool.

PMID- 30283201
TI  - Ultrasound Evaluation of Soft-Tissue Foreign Bodies by US Army Medics.
AB  - Objective: The study's primary objective was to determine army medics' accuracy
      performing bedside ultrasound (US) to detect radiolucent foreign bodies (FBs) in
      a soft-tissue hand model. Secondary objectives included the assessment of US
      stand-off pad effects on soft-tissue FB detection rates and assess established FB
      detectable lower limit size of 2 mm. Methods: Prospective, single blinded,
      observational study of US-naive Army medics' abilities utilizing bedside US to
      detect wooden FBs in a chicken thigh model with or without an US stand-off pad.
      After a 2 h training period, medics' abilities to detect 1-3 mm FB utilizing a
      SonoSite(r) M-Turbo US and 13-6 MHz linear probe were assessed. Results: After a
      2 h training period, 28 medics had a sensitivity and specificity of 73% and 78%
      detecting 1-3 mm FBs utilizing standard US equipment. The medics' sensitivity and
      specificity were both 78% in detecting radiolucent FBs 2 mm and larger without a
      stand-off pad. The sensitivity and specificity decreased to 48%, 62%, and 67%
      when utilizing a stand-off pad to detect 1, 2, and 3 mm soft-tissue FBs. Sub 2 mm
      detection rates decreased from 82% for 2 mm FB to 64% for 1 mm FBs without
      utilizing a stand-off pad. Conclusion: Army medics with minimal US experience
      successfully identified FBs embedded in hand models with accuracies similar to
      radiologists and emergency medicine physicians. However, radiolucent FB detection
      sensitivity and specificity decreased in US-naive Army medics utilizing stand-off
      pads. In addition, this study reconfirmed the lower limit of FB detection rates
      at 2 mm. These results support Army medics' utilization of US to evaluate for
      superficial radiolucent FBs of the hand.

PMID- 30283202
TI  - Large Multilocular Cystic Lesions in the Uterine Cervix: Differential Diagnosis
      and Significance.
AB  - Introduction: Cervical nabothian cysts are common in women of reproductive age.
      Although cysts are generally small and asymptomatic, large ones are extremely
      rare and may be misdiagnosed as malignancy. Case Study: We report a case of large
      multiple complex nabothian cyst, which was suspected as malignant one on imaging
      and examination. Pelvic examination and ultrasonography revealed ballooned cervix
      with multiple large complex nabothian follicles. There was an associated large
      adnexal mass with ascites. The patient was treated with total hysterectomy and
      omentectomy after aspiration of the fluid from the cervical cysts for debulking
      and limiting complications. Pathology revealed granulosa cell ovarian tumor,
      omental panniculitis, and cervical nabothian follicles. Conclusion: Large
      nabothian cysts should be kept in mind for differential diagnosis of cervical
      tumors. Ultrasonography is of value for the diagnosis of giant nabothian cysts
      and can aid in exclusion of malignancy. Differentiation between a malignant
      cystic lesion, such as an adenoma malignum, and a benign cystic lesion is crucial
      but difficult. Cervical nabothian follicles can be multiple and attain a large
      size up to 4 cm each. It is commonly benign but we should keep in mind the rare
      adenoma malignum on imaging and histopathology.

PMID- 30283203
TI  - Curvilinear Probe Endobronchial Ultrasound for Sampling of Parenchymal Lung
      Lesions.
AB  - Lung cancer is the leading cause of cancer related deaths in most countries. It
      can frequently be mimicked by other nonmalignant pulmonary lesions; and
      therefore, in the case of radiologically localized lesions a pathological
      diagnosis is preferable before proceeding to surgical resection. Curvilinear
      probe endobronchial ultrasound is widely used to sample lymph nodes, but in this
      case, we report that it can be beneficial for sampling parenchymal lung lesions
      not accessible at bronchoscopy in the absence of lymphadenopathy.

PMID- 30283204
TI  - Sonographic Diagnosis of a Colovesical Fistula Due to Sigmoid Colon Cancer.
AB  - Based on sonographic findings, colovesical fistula was diagnosed in a 71-year-old
      man with sigmoid colon cancer. Gray-scale sonography revealed an irregular
      thickening of the sigmoid colon wall abutting the urinary bladder which also
      showed thickening in the region of contact. Color Doppler sonography showed a
      twinkling artifact within the thickened bladder wall. Contrast-enhanced computed
      tomography scan showed luminal communication between the sigmoid colon and the
      bladder in the region of thickening.

PMID- 30283205
TI  - Color Doppler Ultrasonography to Evaluate Hypoechoic Areas in Pressure Ulcers: A
      Report of Two Cases.
AB  - Ultrasound (US) is frequently used for evaluating inflammation of subcutaneous
      tissue caused by pressure ulcers (PUs), but color Doppler mode (CDM) helps to
      better identify inflammatory edema in subcutaneous fat and necrotic tissue in
      PUs. We report two cases where inflammatory edema in subcutaneous fat and
      necrotic tissue in PUs are identified using small US equipment with CDM. Case 1 -
      An 82-year-old male presented with cerebral infarction and a Category III PU in
      the sacral region. B-mode gray-scale US imaging (B-mode imaging) revealed a
      thickened layer of subcutaneous fat with fat lobules and homogeneous cobblestone
      appearance with fluid accumulation within the echo-free space. CDM did not
      identify any color signal (CS) in hypoechoic areas. Case 2 - A 29-year-old female
      presented with cytopenia and decreased renal function with a Category IV PU with
      undermining in the coccyx region. B-mode imaging distinguished the necrotic
      tissue, indicating a diffuse hypoechoic area with no layers, unclear borders, and
      uneven gray level (cloud-like image) in the subcutaneous fat. Similar B-mode
      imaging findings were obtained in inflammatory edema with cobblestone appearance.
      CDM did not detect a CS in the hypoechoic areas but confirmed peripheral
      hypervascularity. CDM imaging identified inflammatory edema in the subcutaneous
      fat and necrotic tissue in PUs. Specifically, CDM may better evaluate early-stage
      PUs with necrotic tissue by distinguishing necrosis from intense inflammatory
      edema.

PMID- 30283206
TI  - Ultrasound-Guided Aspiration of a Paralabral Cyst at the Spinoglenoid Notch with
      Suprascapular Nerve Compressive Neuropathy.

PMID- 30283207
TI  - Comment on An Intrauterine Gestational Sac Surrounded by Thin Myometrium at
      Fundus.

PMID- 30283208
TI  - Reply to Comment on An Intrauterine Gestational Sac Surrounded by Thin Myometrium
      at Fundus.

PMID- 30283209
TI  - Skeletal Defect at Mid-trimester Ultrasound Scan.

PMID- 30283210
TI  - A Female Laborer with Right Anterior Shoulder Pain.

PMID- 30283211
TI  - CME Test.

PMID- 30283213
TI  - A mean score method for sensitivity analysis to departures from the missing at
      random assumption in randomised trials.
AB  - Most analyses of randomised trials with incomplete outcomes make untestable
      assumptions and should therefore be subjected to sensitivity analyses. However,
      methods for sensitivity analyses are not widely used. We propose a mean score
      approach for exploring global sensitivity to departures from missing at random or
      other assumptions about incomplete outcome data in a randomised trial. We assume
      a single outcome analysed under a generalised linear model. One or more
      sensitivity parameters, specified by the user, measure the degree of departure
      from missing at random in a pattern mixture model. Advantages of our method are
      that its sensitivity parameters are relatively easy to interpret and so can be
      elicited from subject matter experts; it is fast and non-stochastic; and its
      point estimate, standard error and confidence interval agree perfectly with
      standard methods when particular values of the sensitivity parameters make those
      standard methods appropriate. We illustrate the method using data from a mental
      health trial.

PMID- 30283214
TI  - Real-time Ultrasound Thermography and Thermometry.

PMID- 30283212
TI  - High Hydrostatic Pressure Induces a Lipid Phase Transition and Molecular
      Rearrangements in Low-Density Lipoprotein Nanoparticles.
AB  - Low-density lipoproteins (LDL) are natural lipid transporter in human plasma
      whose chemically modified forms contribute to the progression of atherosclerosis
      and cardiovascular diseases accounting for a vast majority of deaths in
      westernized civilizations. For the development of new treatment strategies, it is
      important to have a detailed picture of LDL nanoparticles on a molecular basis.
      Through the combination of X-ray and neutron small-angle scattering (SAS)
      techniques with high hydrostatic pressure (HHP) this study describes structural
      features of normolipidemic, triglyceride-rich and oxidized forms of LDL. Due to
      the different scattering contrasts for X-rays and neutrons, information on the
      effects of HHP on the internal structure determined by lipid rearrangements and
      changes in particle shape becomes accessible. Independent pressure and
      temperature variations provoke a phase transition in the lipid core domain. With
      increasing pressure an inter-related anisotropic deformation and flattening of
      the particle are induced. All LDL nanoparticles maintain their structural
      integrity even at 3000 bar and show a reversible response toward pressure
      variations. The present work depicts the complementarity of pressure and
      temperature as independent thermodynamic parameters and introduces HHP as a tool
      to study molecular assembling and interaction processes in distinct lipoprotein
      particles in a nondestructive manner.

PMID- 30283215
TI  - Crash Characteristics and Pattern of Motorcycle Related Facial Bone Fractures in
      a Sub-Urban Nigerian Teaching Hospital.
AB  - Context: Recent studies indicated that significant proportion of facial fractures
      attributed to road traffic mishaps in the middle- and low-income countries are
      caused by motorcycle (MC) crashes. However, there is limited information on crash
      characteristics of such injuries. This study was designed to examine the crash
      characteristics, pattern of fracture, and sociodemographics of patients with
      facial bone fractures due to MC crashes in our institution. Subjects and Methods:
      Data on patients' sociodemographics, pattern of presentation, type(s) of
      fracture, patient status, crash characteristics, level of consciousness, and
      treatment offered were collected and analyzed. Results: A total of 151 patients,
      aged 7-59 years were reviewed during the study period. A male preponderance was
      observed (M:F = 4:1) and the patients were predominantly motorcyclists (64.8%, n
      = 98). The most common mechanism of crash was collision with another MC (51.6%, n
      = 78). A total of 194 fractures were reviewed and the mandible (58.8%, n = 114)
      was more commonly affected than the midface (41.2%, n = 80). The predominant site
      on the mandible was the body (31.6%) while zygoma (32.5%) was the most affected
      part of the midface. Patient status was found to have a statistically significant
      relationship with loss of consciousness (P = 0.02). Eighty-two fracture sites
      (42.3%) were managed with open reduction and internal fixation. Conclusions:
      Facial bone fractures occur in a significant proportion of MC crashes and riders
      are predominantly affected. In addition, a larger proportion of commuters rarely
      wear crash helmet which could have offered protection. Continual advocacy on
      preventive measures and enforcement of road safety regulations is hereby advised.

PMID- 30283216
TI  - Histological Characteristics of Breast Lesions in Uyo, Nigeria.
AB  - Background: The breast is a common site for pathologies which predominantly
      involves the female breast. While benign diseases are more common, malignancies
      are of utmost concern for the patient, clinician, and the pathologist. Aim: The
      aim of this study is to audit the clinical and pathological features of patients
      with breast lumps in a tertiary center in Nigeria. Materials and Methods: This is
      a retrospective observational study of histologically diagnosed breast lumps over
      a period of 8 years. Results: Lumps were common in the 20-39 years age group
      (>50%), with a mean age of 34.95 years. Females accounted for 759 (98.1%) of
      cases. In 467 (60.4%) cases, the lumps measured >5 cm and only 175 (22.6%) cases
      presented to the surgeon within 12 weeks of noticing a breast lump. Ninety-one
      (11.8%) cases also presented with axillary lymph nodes, breast pain 79 (10.2%),
      peau d' orange 56 (7.2%), and ulceration 47 (6.1%). Benign breast disease (BBD)
      occurred in 401 (51.8%) cases and malignant breast diseases (MBD) occurred in 344
      (44.3%) of cases. Conclusion: BBD and MBD are common among the young in Uyo.
      Lumps are the primary complaint and late presentation is the norm.

PMID- 30283217
TI  - Efficiency of Ultrasonography in Swellings of Orofacial Region.
AB  - Introduction: Ultrasonography (USG) is found to be important in identifying
      various soft-tissue pathologies in the orofacial region. Therefore, its features
      should be studied and documented in these lesions so that a more appropriate
      provisional diagnosis can be made. Aim: This study aims to study ultrasonographic
      features in various kinds of swellings in the orofacial region. Materials and
      Methods: The study grouped consists of 30 patients of both sexes (20 males and 10
      females) with an age range of 15-70 years complaining of swellings in the
      orofacial region. All the patients in the study were explained the need of tests
      and subjected to clinical, ultrasonographic, and histopathologic examination.
      Sonosite Micromaxx sonography machine was used with a linear array transducer of
      13-6 MHz frequencies. Ultrasonographic diagnosis is then correlated with clinical
      and histopathologic diagnosis. Chi-square test and contingency coefficient tests
      were used. Results: A significant association was observed between clinical and
      ultrasonographic diagnoses (contingency = 0.872, P < 0.05) and between
      ultrasonographic and histopathologic diagnoses (contingency = 0.904, P < 0.05).
      There was 100% congruency between clinical diagnosis and ultrasonographic
      diagnosis in all the cases except in cases of cysts, abscess, and sialadenitis.
      Reliability of USG was found to be 97% in diagnosing all the cases with respect
      to histopathological diagnosis, while it was 90% with respect to clinical
      diagnosis. Conclusion: USG was found to be a reliable diagnostic modality in the
      diagnosis of orofacial swellings.

PMID- 30283218
TI  - Radiographic Evaluation of Anterior Loop of Inferior Alveolar Nerve: A Cone-Beam
      Computer Tomography Study.
AB  - Background: A well awareness of the variation of inferior alveolar canal is
      mandatory to avoid iatrogenic complication. This study was conducted among 90
      patients to determine variation in inferior alveolar nerve (IAN) loop through
      cone-beam computed tomography (CBCT) images. Materials and Methods: CBCT images
      of 90 patients were involved in this study. All images were studied by the expert
      radiologist to see Type I, Type II, and Type III pattern of IAN canal (IANC).
      Results were subjected to statistical analysis for correct inferences. Results:
      Forty males and 50 females were included in the study. The difference was
      statistically nonsignificant (P = 0.5). Type I pattern was seen in 26 patients,
      Type II in 19, and Type III in 45 patients. The difference was statistically
      significant (P < 0.05). The most prevalent pattern was Type III (males - 15 and
      females - 30), followed by Type I (males - 14 and females - 12) and Type II
      (males - 11 and females - 8). There was statistical significance difference
      between males and females in Type II (P < 0.05). Conclusion: The anterior loop of
      IAC is quite common and IANC may show variation in structure. The most common
      pattern recorded was Type III. CBCT is very useful in the detection of IANC.

PMID- 30283219
TI  - A Clinical Study on Comparative Evaluation of the Effectiveness of Carbamazepine
      and Combination of Carbamazepine with Baclofen or Capsaicin in the Management of
      Trigeminal Neuralgia.
AB  - Background: Trigeminal neuralgia (TN) is characterized by recurrent attacks of
      lancinating pain in the trigeminal nerve distribution. Various medicinal and
      surgical procedures have been utilized for the treatment of TN. Over the time,
      several drugs other than carbamazepine have been used but none of them have shown
      satisfying results. Objective: The objective of the study is to evaluate the
      effectiveness of carbamazepine and combination of carbamazepine with baclofen or
      capsaicin in the management of TN. Materials and Methods: A total of 45 patients
      diagnosed with TN were randomly divided into three groups. The patients were
      prescribed carbamazepine in Group 1, carbamazepine and baclofen in Group 2, and
      carbamazepine and capsaicin in Group 3. All the patients were followed on the 7th
      day, 15th day, and 1-month period to evaluate the response to the drugs. Data
      were subjected to statistics. Results: The results are composed of a total of 45
      patients (15 in each group). The mean visual analogue scale scores were
      calculated for each group at day 0, 7th day, 15th day, and 30 days, and it was
      found that there was statistically significant reduction of pain (P < 0.001) in
      all the three groups at different intervals. At day 7, comparative percentage
      reduction of pain in both groups was not statistically significant. At 15-days
      and 30 days, percentage change in pain reduction in Group 1 was 42.3% and 48.0%
      respectively and in Group 2 it was found to be 60.3% and 83.4%, respectively. The
      reduction in pain percentage was found to be statistically significant.
      Similarly, Group 1 was compared to Group 3, significant reduction of pain was
      found for carbamazepine-capsaicin combination at 30-day interval but the
      comparative reduction of pain at 7th day and 15th day was not statistically
      significant. Conclusion: Carbamazepine in combination with baclofen is more
      efficient and effective in reducing pain in TN patients, followed by
      carbamazepine-capsaicin combination compared to carbamazepine alone.

PMID- 30283220
TI  - Evaluation of Immunohistochemical Profile of Breast Cancer for Prognostics and
      Therapeutic Use.
AB  - Introduction: Breast cancer is leading cancer in women, and the incidence of
      breast cancer in India is on the rise. The most common histologic type of breast
      cancer is infiltrating ductal carcinoma. Prognostic and predictive factors are
      used in the management of breast cancer. Estrogen receptor (ER), progesterone
      receptor (PR), and human epidermal growth factor receptor-2 (HER2/neu) are
      immunohistochemical markers of prognosis as well as predictors of response to
      therapy. Aims and Objectives: The study was conducted to evaluate ER, PR, and
      HER2/neu expressions in invasive ductal carcinomas of the breast by
      immunohistochemistry, to explore the correlation of these markers to each other
      and to various clinicopathological parameters: age of the patient, histological
      grade, tumor size, and lymph node metastasis. Materials and Methods: This
      prospective study was conducted on 100 cases of infiltrating ductal carcinoma.
      Slides were prepared from blocks containing cancer tissue, and
      immunohistochemical staining was done for ER, PR, and HER2/neu expressions.
      Interpretation of expressions was done using Allred scoring system for ER/PR and
      the American Society of Clinical Oncology/College of American Pathologists
      guidelines for HER2/neu. Statistical analysis was performed to determine the
      statistical significance by applying Chi-square test. Results: Majority of tumors
      were ER and PR positive and HER2/neu negative. ER and PR correlated significantly
      with age, tumor size, and tumor grade; whereas, HER2/neu correlated significantly
      with tumor size only. No association was seen with axillary lymph node
      metastasis. ER and PR expression correlated with each other, but none correlated
      with HER2/neu. Conclusions: As the majority of the tumors are ER, PR positive and
      since ER and PR correlate with each other as well as with age, tumor size, and
      grade. Therefore, routine assessment of hormone receptors is recommended for
      prognostic and therapeutic information in breast cancer cases.

PMID- 30283221
TI  - Tumor Necrosis Factor-Alpha and Interleukin-1 Alpha as Predictors of Survival in
      Peritonitis: A Pilot Study.
AB  - Context: Peritonitis induces an inflammatory response characterized by the
      elevation of various cytokine levels. Included in this cascade of cytokines are
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1alpha). The
      outcome of patient care may be associated with the pattern of elaboration of
      these cytokines. Aim: The aim of this study was to describe the pattern of
      cytokine response (TNF-alpha and IL-1alpha) in the course of peritonitis and
      evaluate them as predictors of mortality in peritonitis. Setting and Design: This
      was a prospective study conducted in the Division of Gastrointestinal Surgery,
      University College Hospital, Ibadan. Methods: Consenting patients with clinical
      diagnosis of generalized peritonitis over a 6-month period (July to December
      2015) were recruited. The serum samples of these patients were obtained at
      presentation, immediately after surgery, and 24 h and 48 h after surgery with a
      follow-up period of 30 days. Results: Twenty-six samples out of thirty could be
      analyzed. Serum TNF-alpha and IL-1alpha levels were both elevated at presentation
      in all patients. However, the patterns of change after intervention varied
      between the survivors and nonsurvivors. Conclusion: Peritonitis triggers a
      simultaneous increase in serum levels of TNFalpha and IL-1alpha. Lower serum
      level of TNF-alpha is associated with survival, while on the contrary, higher
      level of IL-1alpha is associated with survival.

PMID- 30283223
TI  - Emergency Ileo-cecal Anastomosis with Inclusion of Appendicular Stump in Terminal
      Ileal Pathology: A Newer Approach.
AB  - Background: In emergency settings, several surgical procedures are described
      while dealing with pathology of terminal ileal lying within 15 cm of the
      ileocecal valve, but there is still confusion and controversy over the optimal
      surgical treatment. Methods: A nonrandomized study of 210 patients with near
      terminal ileal pathology (within 15 cm) was carried out over a period of 10
      years. The study included 112 cases in which an ileocecal anastomosis with
      inclusion of appendicular stump was used in terminal ileal pathologies, and in
      rest 98 cases, other surgical procedures were used. The outcomes were measured in
      relation to postoperative complications and mortality. Results: Postoperative
      complications encountered in emergency ileocecal anastomosis with the inclusion
      of appendicular stump were wound infection in 31 patients (34.72%), respiratory
      complications in 10 patients (11.2%), septicemia in 6 patients (6.72.%), and
      anastomotic leak in one patient (1.12%). Conclusion: The technique of ileocecal
      single-layer anastomosis with the inclusion of appendicular stump was found to be
      very effective in dealing this common problem and had less morbidity and
      mortality.

PMID- 30283222
TI  - Use of the World Health Organization Surgical Safety Checklist by Nigerian
      anesthetists.
AB  - Background: Surgery and anesthesia are essential parts of global healthcare.
      Surgical intervention has been largely beneficial but remains associated with
      significant morbidity and mortality. The increasing complexity of surgical
      interventions has made providers more prone to avoidable errors. The World Health
      Organization Surgical Safety Checklist (WHO SSC) was disseminated worldwide with
      the aim of reducing perioperative morbidity and mortality. Objective: There is a
      paucity of data to assess awareness and use of WHO SSC in low- and middle-income
      countries. The aim of this study is to evaluate the knowledge and use of WHO SSC
      by Nigerian anesthetists. Methodology: A structured self-reporting questionnaire
      was distributed to Nigerian physician anesthetists. One hundred and twenty-two
      questionnaires were distributed with 102 completed reflecting a response rate of
      83.6%. Results: Awareness of the WHO SSC was reported by 93.1% of the
      respondents. Routine use of the checklist was reported by 62.7% of the
      respondents mostly in the teaching hospitals compared with the general hospitals
      and comprehensive health centers (86.2%, 23.3% and 14.3%, P = 0.0001). The
      respondents who had a perception that WHO SSC does not prevent errors were the
      least likely to use it (odds ratio: 0.08, P = 0.0117). Conclusion: This study
      identified a high level of awareness and use of the WHO SSC by physician
      anesthetists in Nigeria. However, its use is mostly use of The WHO SSC list by
      Nigerian anesthetists in teaching hospitals.

PMID- 30283224
TI  - Role of Hunger Hormone "Ghrelin" in Long-Term Weight Loss Following Laparoscopic
      Sleeve Gastrectomy.
AB  - Introduction: Laparoscopic sleeve gastrectomy (LSG) has become a popular weight
      loss technique in morbidly obese patients. The aim of our study was to evaluate
      the changes in plasma ghrelin levels in relation to weight loss following LSG and
      to study the efficacy of LSG in terms of long-term glycemic control and
      resolution of diabetes. Methodology: The study was conducted on 70 morbidly obese
      patients (body mass index [BMI] >40 kg/m2) or severely obese patients (BMI >35
      kg/m2) with comorbidities who underwent LSG in Dayanand Medical College and
      Hospital, Ludhiana, India. Ghrelin levels were measured preoperatively and
      postoperatively at 1 week, 3 months, and 6 months along with measurements of
      various weight loss parameters and glycosylated hemoglobin. Results: A
      significant decrease in plasma ghrelin levels was observed in relation to the
      mean weight and percentage excess weight loss at 3 months postoperatively.
      However, at 6 months, fall in ghrelin reached a plateau phase while weight loss
      was still sustained and significant. There was a significant fall in glycosylated
      hemoglobin levels with patients achieving good control/resolution of diabetes
      Type II. Conclusion: LSG is an effective weight loss surgery and brings about
      excellent weight loss in morbidly obese individuals in addition to achievement of
      good glycemic control in diabetic individuals. Serum levels of ghrelin fall
      significantly after sleeve gastrectomy. However, long term implications of
      ghrelin induced weight loss cannot be elucidated.

PMID- 30283225
TI  - Maxillectomy and Quality of Life: Experience from a Nigerian Tertiary
      Institution.
AB  - Introduction: Maxillectomy is a surgical procedure for managing tumors affecting
      the maxilla; the goal of maxillectomy however should not be limited to tumor
      extirpation but should include restoration of oronasal function and facial
      contours, as failure to do these may give rise to psychosocial and functional
      challenges. This study aimed to appraise the pattern of maxillectomies,
      challenges of management, and quality of life (QOL) of a proportion of the study
      population. Materials and Methods: This was a cross-sectional study carried out
      at the Department of Oral and Maxillofacial Surgery, University College Hospital,
      Ibadan. Patients' case files from year 2000 to 2016 were retrieved and reviewed.
      Data extracted for analysis included age, gender, site of lesion, and histologic
      diagnosis; lesions were grouped as benign or malignant. Contacts were made with
      patients or their next of kin for a clinic review appointment where QOL was
      assessed with the University of Washington Quality of Life version 4
      Questionnaire. Data were analyzed and result presented as means and frequencies.
      Results: Out of the 78 cases of maxillectomy recorded in the department within
      the study period, records were available and adequate in 67 cases. There were 37
      (55.2%) females with a mean age of 35.88 +/- 14.9 years. Swelling was the most
      common reason for presentation (63, 94%). The mean period between onset of
      disease and presentation for treatment was 3.66 +/- 3.35 years. Distribution of
      lesions was benign 35 (52.2%) and malignant 32 (47.8%). Hemi-maxillectomy was the
      commonest surgical procedure (23, 34.8%). While majority had some prosthetic
      rehabilitation, 31 participants (48.5%) obtained no prosthesis. Eight
      participants gave scores of >=75% when comparing their present health-related QOL
      (HR-QOL) with a month before surgery; the overall QOL was >=60%. However, HR-QOL
      and overall QOL in the last 7 days before assessment were rated as good in 55.6%
      and 66.7%, respectively. Chewing was the most important domain to participants.
      Conclusion: The pattern of presentation and indications for maxillectomy in this
      series are similar to that from previous studies. The uptake of prosthetic
      rehabilitation was low and overall QOL was rated as fair. QOL should be
      considered as part of treatment outcome measure for maxillectomy.

PMID- 30283226
TI  - Mixed Adenoneuroendocrine Carcinoma of the Esophagus: A Case Report and Review of
      the Literature.
AB  - The most frequent presentation of esophageal cancer is adenocarcinoma and
      squamous cell carcinoma. In recent years, the latter has decreased its incidence
      increasing the adenocarcinoma. Currently, another type of tumor with a much lower
      incidence has been described, which has a neuroendocrine component along with
      another exocrine glandular component and has been classified since 2010 as mixed
      adenoneuroendocrine carcinoma (MANEC). We present the case of a 68-year-old male
      with a history of dyspepsia and epigastric pain who after performing a
      gastroscopy, was diagnosed with a malignant neoplasm of the esophagus. The
      patient underwent a total esophagectomy with reconstruction by tubular
      gastroplasty with cervical anastomosis. The final result of the piece after
      immunohistochemistry revealed that the tumor was composed of one component of
      adenocarcinoma in 60% together with another component compatible with
      neuroendocrine in 40%. With these findings and according to the World Health
      Organization classification of 2010 was diagnosed as esophageal MANEC. MANECs are
      rare tumors, described in other locations of the digestive tract, the esophagus
      being an infrequent location. Its preoperative diagnosis is difficult, and it is
      not until the final analysis of the complete piece by means of specific
      immunohistochemical techniques when its diagnosis can be established. Its
      treatment is fundamentally surgical, whereas the adjuvant therapeutic schemes
      with chemotherapy are not well defined at present because of their low incidence.

PMID- 30283227
TI  - Secretory Carcinoma of the Breast in a 20-year-old Male: Case Report and Review
      of Literature.
AB  - Secretory breast carcinoma (SBC) is a very rare low-grade subtype of breast
      carcinoma. It was initially termed "juvenile breast cancer," but it is now known
      to occur in adults of both sexes, and only few male cases have been reported in
      the literature. SBC is of importance because of its unique morphology and
      excellent prognosis. We report here a case in a 20-year-old male presenting with
      right pedunculated and ulcerated breast mass with associated contact bleeding.
      Histopathology was performed and it revealed a secretory carcinoma. This tumor is
      morphologically characterized by the presence of abundant eosinophilic secretions
      in intracellular vacuoles and intercellular spaces. The objective of this article
      is to review the epidemiological and clinical aspect of secretory carcinoma from
      a case report and literature review.

PMID- 30283228
TI  - Unsuspected Skin Metastasis of Adenocarcinoma of the Prostate in a Patient on
      Goserelin (Zoladex).
AB  - Prostate cancer remains the most common noncutaneous cancer in men, especially in
      this era of prostate-specific antigen assay. Prostate cancer metastases have been
      known to commonly affect the lymphatics, bones, and lungs. Prostate cancer
      metastasis to the skin is very rare (<1%) and often signifies a terminal disease.
      Involvement of the skin has been thought to be through lymphatic spread by
      embolization or permeation, hematogenous spread, and implantation during surgery
      (port site in radical prostatectomy). We report a 74-year-old man on management
      for advanced prostate cancer with subcutaneous goserelin (Zoladex) but developed
      skin metastasis in the course of treatment. The skin metastasis in our patient,
      however, was initially localized to the site of the regions of subcutaneous
      goserelin injection that we imagined if there is a link between the two. We
      reviewed the literature and currently found no connection. Is there truly a link?

PMID- 30283229
TI  - Postcraniectomy Cranioplasty Using Autologous Split Calvarial Graft.

PMID- 30283230
TI  - Using Semantic Web Technologies to Enable Cancer Genomics Discovery at Petabyte
      Scale.
AB  - Increased efforts in cancer genomics research and bioinformatics are producing
      tremendous amounts of data. These data are diverse in origin, format, and
      content. As the amount of available sequencing data increase, technologies that
      make them discoverable and usable are critically needed. In response, we have
      developed a Semantic Web-based Data Browser, a tool allowing users to visually
      build and execute ontology-driven queries. This approach simplifies access to
      available data and improves the process of using them in analyses on the Seven
      Bridges Cancer Genomics Cloud (CGC; www.cancergenomicscloud.org). The Data
      Browser makes large data sets easily explorable and simplifies the retrieval of
      specific data of interest. Although initially implemented on top of The Cancer
      Genome Atlas (TCGA) data set, the Data Browser's architecture allows for seamless
      integration of other data sets. By deploying it on the CGC, we have enabled
      remote researchers to access data and perform collaborative investigations.

PMID- 30283231
TI  - Habitat requirements of endangered species in a former coppice of high
      conservation value.
AB  - Transformation of coppices to high forests has caused fundamental changes in site
      conditions and a decline of many species across Central Europe. Nevertheless,
      some formerly coppiced forests still harbour a number of the declining species
      and have become biodiversity hotspots in the changing landscape. We focused on
      the best preserved remnant of formerly grazed and coppiced subcontinental oak
      forest in the Czech Republic - Dubrava forest near Hodonin. To improve our
      understanding of the ecology of the declining species, we studied local habitat
      requirements of vascular plants most endangered at the national level. We
      recorded vegetation composition and sampled important site variables in plots
      with the largest populations of endangered species and in additional plots placed
      randomly across all major forest habitats. We demonstrated that sites with
      endangered species have a highly uneven distribution in ecological space and
      their species composition is often similar to open-canopy oak forests. Within
      this habitat, the endangered species are concentrated in places with a high light
      availability and high soil pH. Light-demanding species characteristic of
      subcontinental oak forests are the best indicators of these sites, while broadly
      distributed shade-tolerant and nutrient-demanding species avoid them. These
      results support the view that the occurrence of many endangered species in
      Dubrava forest is a legacy of the long history of traditional management that
      kept the canopies open. The light-demanding species are now threatened by ongoing
      successional changes. Therefore, active conservation measures are recommended,
      including opening up the canopies, early thinning of young stands, control of
      expansive and invasive species and understorey grazing or mowing.

PMID- 30283232
TI  - New species of parasitic nasal mites infesting birds in Manitoba, Canada
      (Mesostigmata, Rhinonyssidae).
AB  - Mites (Acari, Acariformes, Parasitiformes) are one of the most diverse and
      abundant groups of arthropods associated with birds. Several families of mites
      have colonised the respiratory tract of birds, the Rhinonyssidae (Mesostigmata)
      being the most diverse. There are 66 species of rhinonyssids (59 named, seven
      undescribed species) reported from Canadian birds. Two new species of
      rhinonyssids were discovered while surveying nasal mites from birds in Manitoba,
      Canada, and are herein described as Sternostomagallowayi sp. n. from the horned
      lark (Eremophilaalpestris), and Vitznyssuserici sp. n. from the common nighthawk
      (Chordeilesminor).

PMID- 30283233
TI  - Cryptic diversity in Andrognathuscorticarius Cope, 1869 and description of a new
      Andrognathus species from New Mexico (Diplopoda, Platydesmida, Andrognathidae).
AB  - Andrognathus is a genus of small, thin-bodied millipedes found in deciduous
      forests of North America. Poorly understood, these organisms inhabit decaying
      wood and have morphologically conserved and difficult-to-identify sexual
      characters that have limited study historically. Recent use of scanning electron
      microscopy has uncovered variation in male genitalia that was previously unknown
      in the genus. The distribution of Andrognathus and the extent of this variability
      across the continent, however, were undocumented, and a wealth of natural history
      collections remained uncatalogued. Here a new species of Andrognathus is
      described from New Mexico, Andrognathusgrubbsi sp. n., natural history
      collections are utilized to create a comprehensive map of the genus, and a
      neotype established for the type species, Andrognathuscorticarius Cope, 1869.
      Analysis of the cytochrome oxidase I gene (COI) for A.corticarius was completed
      for the type series and individuals across the species distribution, but little
      variation was found. Andrognathusgrubbsi sp. n. joins A.corticarius and
      A.hoffmani Shear & Marek, 2009 as the only members of the genus.

PMID- 30283234
TI  - Two new species of the millipede genus Metonomastus Attems, 1937 from the Balkan
      Peninsula (Diplopoda, Polydesmida, Paradoxosomatidae).
AB  - In addition to the eleven previously known species of the Mediterranean genus
      Metonomastus, two more species are described: M.petrovi sp. n., from the Rhodopi
      Mts. and Bunardzhik Hill in Bulgaria, and M.radjai sp. n., from the island of
      Mljet in Croatia. The relationships between the congeners and their distributions
      are briefly discussed. All 13 species of the genus are keyed.

PMID- 30283235
TI  - One generic synonym and one new species of Phlaeothripidae from India
      (Thysanoptera).
AB  - Haplothripsshivendraii Tyagi & Kumar, sp. n. is described from Rajasthan state of
      India. The monobasic Austro-oriental genus Dyothrips Kudo is formally synonymised
      with Haplothrips.

PMID- 30283236
TI  - A new species and a key to the species of Corticarina from Guatemala (Coleoptera,
      Latridiidae).
AB  - A new species of Corticarina Reitter, 1881 (Coleoptera: Latridiidae),
      Corticarinaoscargloriorum sp. n. from Guatemala is described and illustrated. The
      differential diagnosis is established in relation to a group of other species of
      the genus.

PMID- 30283237
TI  - A new genus and species of clingfish from the Rangitahua Kermadec Islands of New
      Zealand (Teleostei, Gobiesocidae).
AB  - Flexorincus, new genus and species, is described from 15 specimens (14.0-27.2 mm
      SL) collected from shallow (0-9 meters) intertidal and sub-tidal waters of the
      Rangitahua Kermadec Islands, New Zealand. The new taxon is distinguished from all
      other members of the Gobiesocidae by a combination of characters, including a
      heterodont dentition comprising both conical and distinct incisiviform teeth that
      are laterally compressed with a strongly recurved cusp, an oval-shaped opening
      between premaxillae, a double adhesive disc with a well-developed articulation
      between basipterygia and ventral postcleithra, and many reductions in the
      cephalic lateral line canal system. The new taxon is tentatively placed within
      the subfamily Diplocrepinae but shares a number of characteristics of the oral
      jaws and the adhesive disc skeleton with certain members of the Aspasminae and
      Diademichthyinae.

PMID- 30283238
TI  - Tosanoidesaphrodite, a new species from mesophotic coral ecosystems of St. Paul's
      Rocks, Mid Atlantic Ridge (Perciformes, Serranidae, Anthiadinae).
AB  - During a recent expedition to St. Paul's Rocks, Atlantic Ocean, a distinctive and
      previously unknown species of Anthiadinae was collected at a depth of 120 m. A
      genetic analysis indicated the undescribed species is a member of the genus
      Tosanoides, which was only known to occur in the Pacific Ocean. This new taxon is
      distinguishable from all other Tosanoides species by the following combination of
      characters: soft dorsal fin rays 15-16; anal fin rays 9; ventral scale rows 9-10;
      last dorsal spine the longest (instead first through fourth). Here
      Tosanoidesaphrodite sp. n. is described and illustrated, only known from St.
      Paul's Rocks.

PMID- 30283239
TI  - What is the Potential for Community Currencies to Deliver Positive Public Health
      Outcomes? Case Study of Time Credits in Wisbech, Cambridgeshire, UK.
AB  - There is evidence that increased levels of community engagement and social
      participation can improve population health. Community currencies such as Time
      Credits are one way to support and encourage people to be more involved in their
      local community. As a result, they have attracted investment by local governments
      in the UK, with the hope of finding new ways to work with deprived communities,
      improve individual outcomes that lead to better health, and reduce the use of
      public services at a time of financial austerity. The aim of this research was to
      evaluate the health related outcomes of volunteering through Time Credits in
      Wisbech, Cambridgeshire. The conceptual model developed during the research shows
      how Time Credits were expected to influence some of the social determinants of
      health and, by doing so, enhance health outcomes and reduce health inequalities.
      This in depth empirical study shows the potential of such activity to support
      pathways to better health, but equally demonstrates the challenges in quantifying
      such outcomes and in evidencing any reduction in the use of public services as a
      result.

PMID- 30283240
TI  - 2D:4D digit ratio and religiosity in university student and general population
      samples.
AB  - The ratio of index to ring finger length (2D:4D) is used as a proxy for prenatal
      sex hormone exposure. It has been hypothesised to correlate with religiosity,
      though no published research has explored this possibility. Here, we initially
      examined 2D:4D in relation to self-reported religious affiliation and
      questionnaire measures of general religiosity, spirituality, religious
      fundamentalism, and religious commitment in male (N = 106) and female (N = 105)
      university students (Study 1). Although no significant correlations were observed
      between 2D:4D and the questionnaire measures, females who affiliated with
      organised religions had higher digit ratios compared to agnostic or atheist
      females. Study 2 attempted to replicate these findings in an adult general
      population sample (N = 172 males, N = 257 females), but did not observe
      significant effects in either sex. Overall, these findings suggest that high
      2D:4D may be relatively-specifically associated with religious affiliation in
      young, highly-educated, females.

PMID- 30283241
TI  - Blending computational and experimental neuroscience.
AB  - The launch of the United States' BRAIN Initiative brings with it a new era in
      systems neuroscience that is being driven by innovative neurotechnologies,
      increases in computational power and network-style artificial intelligence. A new
      conceptual framework for understanding cognitive behaviours based on the
      dynamical patterns of activity in large populations of neurons is emerging.

PMID- 30283242
TI  - Prevention of Diabetes: Countless Opportunities and Clear Challenges.
AB  - Prevention of diabetes poses significant challenges; especially when applied as
      public health intervention. While several trials, most importantly Diabetes
      Prevention Program, show that intensive lifestyle modification leading to weight
      loss is the most important intervention, many individuals and some populations
      may show resistance to these interventions. Roadblocks to lifestyle intervention
      alone or in combination include: age, some ethnic groups (e.g., south Asians),
      genetic make-up, and some characteristics of body phenotype. Recent data show
      that non-alcoholic fatty liver disease along with insulin resistance may
      constitute 'metabolically unhealthy phenotype'. These subgroups would need more
      intensive interventions to convert prediabetes to normal glucose regulation.
      Whether 'fatty pancreas' and sarcopenia, latter more often seen in Asian Indians
      and with advancing age, are other phenotypes requiring intensive and different
      interventions (e.g., more resistance exercise in latter) remains to be
      researched. Further, variations in dietary quality (Mediterranean diet enriched
      with extra virgin olive oil, high-protein diets) without changing much of
      calories, provide attractive options for intervention. Many of such innovations
      require more research. Translation of lessons from diabetes prevention studies to
      general population is daunting but possible. However, such community-based
      interventions need substantial human and material resources, which pose hurdles
      in underserved populations and developing countries. In such situations, low-cost
      modalities, for example, use of trained community educators and digital and
      social media, constitute attractive approaches.

PMID- 30283243
TI  - Lifestyle and Pharmacotherapy for Weight Loss in Preventing or Delaying Diabetes.
AB  - Preventing or delaying the conversion of prediabetes to overt diabetes can reduce
      mortality and morbidity rates, improve health-related quality of life, and reduce
      other comorbid complications associated with diabetes. Studies have shown that a
      modest weight loss is one strategy for preventing or delaying diabetes diagnosis.
      First-line therapy in preventing progression of prediabetes to overt diabetes is
      weight loss through lifestyle modifications; however, pharmacotherapy for weight
      loss may be initiated if lifestyle alone is ineffective. The purpose of this
      article is to describe the pharmacotherapeuptic options for weight loss that can
      be used in conjunction with lifestyle in the prevention or delay of diabetes in
      patients with prediabetes.

PMID- 30283244
TI  - Lifestyle Choices Can Augment Female Sexual Well-Being.
AB  - Female sexual wellbeing is complex and it's an important part of a comprehensive
      approach to women's health. Unfortunately, this aspect of health often is not
      discussed during medical appointments which can be isolating for female patients.
      Low libido is the most common female sexual dysfunction. There are multiple
      causes of low libido that may be physical, cultural, emotional, medical
      psychological or due to her relationship with her partner. A healthy lifestyle is
      one way to help women overcome low libido and a few examples include exercise,
      mindfulness and yoga. Ultimately, these lifestyle approaches can enhance sexual
      satisfaction.

PMID- 30283245
TI  - Uncovering the Truth.
AB  - Finding the truth is important. In the field of lifestyle medicine the randomized
      controlled trial has significant limitations. Physicians and patients need to
      know the truth about the healthy lifestyle changes and their ability to prevent
      and reverse disease. To meet this challenge, the American College of Lifestyle
      Medicine has established a committee of experts (HEaLM), under the leadership of
      David Katz to create a level of evidence construct for ranking lifestyle medicine
      evidence that includes evidence from basic science and epidemiologic trials. This
      tool will be used by the new Expert Lifestyle Medicine Panel to create guidelines
      and standards of practice.

PMID- 30283246
TI  - Nutritional Assessment and Intervention to Prevent and Treat Malnutrition for
      Fall Risk Reduction in Elderly Populations.
AB  - The aging US population is increasing, and it is estimated that adults older than
      65 years will make up 20% of the population by 2029 and the proportion of
      individuals in the United States older than 65 years will outnumber individuals
      younger than 18 years. In older adults, accidental falls are the leading cause of
      fatal and nonfatal injuries. Prevalence of chronic conditions such as sarcopenia
      and frailty contribute to the increased risk for fall observed in this
      population. Nutritional status in elderly individuals is a key predictor of both
      frailty and sarcopenia, thus ensuring adequacy in these populations has the
      potential for preventing falls. Poor nutritional status is associated with the
      onset of frailty. Nutrition screening, assessment and interventions can be
      targeted at this age group to overcome treat and prevent malnutrition to minimize
      fall risk.

PMID- 30283247
TI  - Advocating for Behavior Change With Education.
AB  - Education is ubiquitous with clinical care. However, not all education supports
      behavioral change. Education is a broad term that encompasses the process of
      obtaining general knowledge, personal awareness, and skills training. Although
      not sufficient, education is a necessary component for behavior change. This
      article outlines the role of education in behavior change and offers practical
      suggestions for how clinicians can provide education to their patients to help
      them change behavior.

PMID- 30283248
TI  - Prevention of Pediatric Pharmaceutical Poisonings.
AB  - Pediatric poisoning remains a common, preventable childhood injury and incidence
      is on the rise. Child-resistant packaging has been shown to prevent
      pharmaceutical poisoning, but must be applied and used appropriately to be
      effective. Prescription drug use among adults is also increasing and may be
      contributing to the problem through a greater number of medications in the
      child's environment. Drug take back programs are designed to reduce the number of
      unused medications in the home. These programs are expanding and health care
      providers should be aware of and encourage safe drug disposal practices.

PMID- 30283249
TI  - In Search of a Good Night's Sleep: Hormones, Mind, Movement, and Breath.
AB  - Sleep disturbances are common in postmenopausal women and contribute to increased
      morbidity and mortality. Sleep apnea may be underdiagnosed in women, and other
      conditions such as insomnia and restless legs may coexist with sleep apnea. This
      case illustrates the complex interplay of anatomical, hormonal, metabolic and
      psychological factors that can interfere with restorative sleep, and the
      importance of both diagnostic testing and clinical history in identifying which
      combination of therapies will be most beneficial in improving sleep quality and
      quantity.

PMID- 30283250
TI  - Informed Consent: Is It Accompanied by Full Disclosure?
AB  - Informed consent assumes full disclosure has been discussed in its entirety.
      However, is full disclosure ever really achieved? This column discusses how
      lifestyle medicine, both philosophically and ethically, must be a standard
      component of informed consent. Yet despite unequivocal evidence regarding the
      efficacy of lifestyle medicine, few physicians even consider lifestyle medicine
      as a viable option in the informed consent process. Reasons for the lack of
      lifestyle medicine considerations are postulated and a potential solution through
      education of trainees is suggested. How one medical school is addressing the need
      for lifestyle medicine education through several initiatives is discussed. Last,
      we expect that trainees educated in lifestyle medicine will push the momentum
      forward toward the "tipping point" where lifestyle medicine will be a viable
      option in the informed consent process-only then will full disclosure truly be
      achieved.

PMID- 30283251
TI  - Awareness of Cancer Risk: Variation in Measurement Approaches.
AB  - Cancer is a major cause of morbidity and mortality. Diet, nutrition, physical
      inactivity, and obesity have been identified as important contributors to the
      increasing cancer incidence worldwide. To effectively plan interventions to
      reduce cancer incidence and to influence the public's decisions regarding health
      behaviors, it is important for professionals to have an understanding of the ways
      in which people understand risk with regard to development of cancer. Selecting
      an appropriate method to evaluate awareness of cancer risk is an important
      consideration. Quantitative approaches such as surveys may be used to investigate
      awareness of risk, and recall of risk factors as well as recognition of such
      factors may form part of such assessments. Such quantitative methods may be used
      to evaluate risk in different demographic groups, as well as to examine the link
      between risk factors and behavior. Qualitative approaches include in-depth
      interviews, focus groups, and open-ended survey items and may be used to explain
      findings derived using quantitative methods. Mixed methods approaches may also be
      employed, involving use of a survey as well as interviews or focus groups to
      gather in-depth information. Assessment of awareness of cancer risk using an
      appropriate method has important implications for educators, as professionals
      must evaluate understanding of risk factors and tailor messages accordingly for
      educational programs. Ongoing evaluation of awareness is a key part of
      determining the effectiveness of education initiatives and identifying new and
      emerging issues.

PMID- 30283252
TI  - Healthy Living After Cancer Treatment: Considerations for Clinical and Community
      Practice.
AB  - As the number of US cancer survivors now reaches almost 16 million, understanding
      how to care for survivors after cancer treatment has demanded national attention.
      Increasingly, compelling benefits of lifestyle behaviors for cancer prevention
      and control have been demonstrated. In particular, physical activity is
      recommended as a central component of healthy living after cancer treatment.
      However, survivors struggle to achieve recommended physical activity and other
      behaviors for reasons that are still not well understood. Further, as greater
      than 60% of cancer survivors are older than 65 years, there is a unique
      opportunity to increase engagement of older adults in health programs and
      clinical trials. This article considers evidence from two reviews: a review on
      epidemiology studies of lifestyle and cancer and a review on different behavioral
      intervention strategies to achieve positive behavioral changes in cancer
      survivors. Both reviews offer important evidence on the role of lifestyle in life
      after cancer treatment. However, more investigation is needed on the practice of
      lifestyle medicine for cancer survivors, including ways to extend the reach of
      health promotion beyond cancer clinics, to primary care and community settings.

PMID- 30283253
TI  - Integrating Physical Activity Into Clinical Cancer Care.
AB  - Physical activity is an important target for improving health and well-being
      among cancer survivors. Cancer clinicians are uniquely positioned to promote
      physical activity among survivors through follow-up visits for treatment planning
      and surveillance. Providers should prioritize assessment of guideline-concordant
      physical activity and facilitate achievement of physical activity guidelines
      through exercise prescription, goal setting, addressing barriers, and
      capitalizing on support systems.

PMID- 30283254
TI  - Hormonal Contraception and Breast Cancer Risk.
AB  - Contemporary hormonal contraception formulations contain lower doses of estrogen,
      have new synthetic progestin components, and provide novel methods of delivery
      that have not been studied extensively in relation to breast cancer risk. Given
      that hormonal contraception is the leading method of birth control in the United
      States, it is important to reevaluate risk using current formulations. Recent
      studies including contemporary hormonal contraception formulations will be
      described.

PMID- 30283255
TI  - Lifestyle Medicine Inpatient Consultation Services at Loma Linda University
      Health: A Novel Approach in a Tertiary Care Center.
AB  - As a nation facing primary care provider shortages, an expanding chronic disease
      burden, and rising health care costs, lifestyle medicine interventions have
      become critical for patient care and management. The current fee-for-service
      health care system in the United States is designed for delivering acute care but
      has made it challenging to deliver and be reimbursed sufficiently for lifestyle
      interventions that can help prevent and treat chronic disease. Loma Linda
      University Health began to address these concerns through the creation of an
      inpatient consultation service for the neurology rehabilitation stroke team.
      Initiation of the consultation service took 2 years of planning, testing, and
      resource development. Currently, the consultation service operates one half-day
      per week in the rehabilitation hospital utilizing 1 attending physician and 2
      residents. Visiting residents and medical students are also permitted to rotate
      with the new service. In coordination with billing experts, a standard number of
      21.2 to 25.4 RVUs (relative value units) has been established for the half-day
      service. As the service continues to expand, future considerations include adding
      consultation availability to other departments and increasing the consultation
      workforce.

PMID- 30283256
TI  - Shifting the Paradigm.
AB  - Current medical education lacks significant training in the principles and
      practices of lifestyle medicine. In this column, I describe my journey to
      lifestyle medicine, lifestyle medicine education, and what it is going to take to
      shift the educational paradigm away from the current model to one that is focused
      on nutrition and lifestyle behaviors and that is both accessible and effective.

PMID- 30283257
TI  - Lifestyle Medicine Continues to Grow and Thrive.

PMID- 30283258
TI  - Lifestyle Medicine: A Revolution or a Revelation?

PMID- 30283259
TI  - What Is Lifestyle Medicine?
AB  - Lifestyle Medicine is still being defined. The ACLM is making significant
      progress in defining it within the house of medicine. The new American and
      International Boards of Lifestyle Medicine go a long way in identifying the
      clinical parameters for this new specialty. The board review course defines the
      academic corpus in a clear way. Now that Lifestyle Medicine has clear borders it
      needs to be spread throughout the cultures of the world. People in all walks of
      life and levels of responsibility need to hear stories of individuals and
      communities that have their health improved by following the principles of
      Lietyle Medicine.

PMID- 30283260
TI  - Toward a Lifestyle Medicine Approach to Illness Anxiety Disorder (Formerly
      Hypochondriasis).
AB  - Lifestyle medicine may be the most effective way of treating illness anxiety
      disorder (IAD), formerly hypochondriasis. IAD as defined in the DSM-5 can now be
      diagnosed using positive symptoms, which means it is no longer a diagnosis of
      exclusion. Tools used in lifestyle medicine including motivational interviewing
      and mindfulness based stress reduction (MBSR) may be particularly useful in the
      management of IAD.

PMID- 30283261
TI  - Combining Lifestyle Medicine and Positive Psychology to Improve Mental Health and
      Emotional Well-being.

PMID- 30283262
TI  - The Hidden Dangers of Fast and Processed Food.

PMID- 30283263
TI  - Lifestyle Medicine Education Collaborative (LMEd): "Champions of Change" Medical
      School Leaders Workshop.
AB  - The Lifestyle Medicine Education Collaborative (LMEd) hosted the "Champions of
      Change" Medical School Leaders workshop at the 2017 American College of Lifestyle
      Medicine annual conference. Presentations focused on the following: (1)
      accelerating adoption and implementation of lifestyle medicine (LM) education in
      medical schools through collaboration and action networks that produce positive
      results, (2) showcasing medical school champions and their work in LM education
      leadership, and (3) helping participants create a roadmap for how to engage with
      LMEd and implement LM education in their own medical school.

PMID- 30283264
TI  - Common Misconceptions in the Nutritional Management of Athletes.
AB  - Athletes today face a multitude of competing voices with health claims and
      products to enhance performance. This has led to both confusion and
      misconceptions about healthy dietary practices for athletes. Research has
      demonstrated that athletes do not understand the recommended nutritional
      requirements necessary for health. Further, improper study methods and research
      design can create and propagate misconceptions about how athletes view their own
      health and personal sacrifices. These misconceptions not only influence attitudes
      and recommendations by healthcare providers and coaches but can also affect
      legislation. Healthcare providers, coaches and trainers have the opportunity to
      positively influence healthy nutritional lifestyles in athletes. Research has
      demonstrated that the balance of expert power and referent power have been shown
      to emphasize personal empowerment and long term change.

PMID- 30283265
TI  - Clinical Lifestyle Medicine Strategies for Preventing and Reversing Memory Loss
      in Alzheimer's.
AB  - Alzheimer's disease (AD) is the most common form of dementia and currently
      affects over 5 million Americans and 30 million individuals worldwide.
      Unfortunately, the current approach to treating AD provides nothing more than a
      marginal, unsustained, symptomatic effect, with little or no effect on disease
      progression itself. To attain effective improvements in AD, one must determine
      risk factors, address the underlying causes, and focus on a combination of
      functional and lifestyle medicine strategies that provide a comprehensive,
      programmatic, and network-based approach that is sufficient to achieve epigenetic
      transformation and neurologic healing through its multiple and necessary
      synergistic components. Rather than normalizing metabolic parameters, the focus
      is on optimization of each metabolic parameter. Papers published by research
      neurologist, Dr Dale Bredesen have documented that symptoms of mild cognitive
      impairment and early AD may often be reversed within 6 months after initiating a
      comprehensive, functional and lifestyle medicine-focused program. The purpose of
      this article are as follows: 1. Shed light on a promising clinical protocol that
      focuses on a comprehensive functional and lifestyle medicine approach to treating
      mild cognitive decline and Alzheimer's disease; 2. Identify the Bredesen Protocol
      testing, diagnostic and treatment guidelines; 3. Review several case studies and
      discuss the promising results of the program. Although published case studies
      such as those reported here are relatively few, clinicians applying these
      comprehensive strategies have reason to expect improvement in their patients.
      Lifestyle medicine can be a source of greatly needed hope for those suffering
      with cognitive decline.

PMID- 30283267
TI  - The Lifestyle Medicine Outpatient Clinic at Loma Linda University Health.
AB  - Medical management of chronic health concerns relies heavily on behavioral
      change, most specifically medication adherence. Yet approximately 50% of patients
      with chronic illnesses are not thought to take their medications as prescribed.
      Moreover, it is recognized that lifestyle and behavioral changes can reduce the
      need for medication. It is well documented that patient outcomes and their
      success in achieving behavioral change is improved with engagement and support
      from a medical care team. As the inpatient lifestyle medicine service was being
      conceptualized at Loma Linda University Health (LLUH), it became apparent that an
      outpatient service would be necessary for follow-up care of the patients and
      support the lifestyle medicine treatments initiated in the hospital.
      Additionally, an outpatient clinic would be available to the patient population
      at Loma Linda and potentially prevent hospitalizations, morbidity, and mortality
      with proactive lifestyle medicine treatment. The initial outpatient clinic opened
      in February 2017 and was soon expanded to meet patient demand. Currently, the
      LLUH Lifestyle Medicine Outpatient Clinic is available 5 days a week, utilizing 5
      physicians.

PMID- 30283266
TI  - Worksite Nutrition: Is a Nutrient-Dense Diet the Answer for a Healthier
      Workforce?

PMID- 30283268
TI  - From Infectious Diseases to Lifestyle Medicine: My Personal Journey.

PMID- 30283269
TI  - Optimized Antigen Matching - Chances and Challenges in Molecular Times.

PMID- 30283271
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1159/000490122.].

PMID- 30283270
TI  - The Impact of Using Genotyped Reagent Red Blood Cells in Antibody Identification.
AB  - Background: The detection and identification of antibodies to red blood cell
      (RBC) antigens is one of the most important and challenging issues in transfusion
      medicine. Up to date there are 354 RBC antigens recognized by the International
      Society of Blood Transfusion (ISBT). The reagent RBCs used in commercial antibody
      screening and identification panels however are usually serologically typed for
      up to 40 clinically important antigens. Thus the identification of many antibody
      specificities remains impossible when using reagent RBCs with only limited
      information about their antigens. To improve the pre-transfusion diagnostics, we
      developed antibody identification panels with reagent RBCs serologically typed
      for 26 antigens and additionally genotyped for 30 blood group alleles. Methods:
      The reagent RBCs in the panels were characterized serologically for the
      clinically most significant 'standard' antigens. The reagent RBC donors were
      additionally genotyped by using in-house PCR-SSP methods. The antibody
      identification was performed in the indirect antiglobulin test using untreated
      and papain-treated RBCs in the gel technique. Antibodies identified due to the
      genotype information were confirmed by serology using appropriate reference RBCs.
      Results: Within a time period of 3 years and 8 months, 16,878 blood samples from
      8,467 patients were tested in our reference laboratory. In total, 21 different
      antibodies from 10 different blood group systems could be identified in 126
      patients (1.5%) due to the genotype information obtained for the reagent RBCs.
      Antibodies to antigens from the Knops system (53 patients; 42%, 8 patients with
      anti-Knb) and to Cartwright antigens (31 patients; 25%) were the most frequent.
      Conclusion: The use of genotyped reagent RBCs in antibody identification panels
      extends the range of detectable antibody specificities, accelerates the antibody
      identification, and improves the pre-transfusion diagnostics.

PMID- 30283272
TI  - Extended Donor Typing by Pooled Capillary Electrophoresis: Impact in a Routine
      Setting.
AB  - Background: PCR with sequence-specific priming using allele-specific fluorescent
      primers and analysis on a capillary sequencer is a standard technique for DNA
      typing. We aimed to adapt this method for donor typing in a medium-throughput
      setting. Methods: Using the Extract-N-Amp PCR system, we devised a set of eight
      multiplex allele-specific PCR with fluorescent primers for Fya/Fyb, Jka/Jkb, M/N,
      and S/s. The alleles of a gene were discriminated by the fluorescent color; donor
      and polymorphism investigated were encoded by product length. Time, cost, and
      routine performance were collated. Discrepant samples were investigated by
      sequencing. The association of new alleles with the phenotype was evaluated by a
      step-wise statistical analysis. Results: On validation using 312 samples, for
      1.1% of antigens (in 5.4% of samples) no prediction was obtained. 99.96% of
      predictions were correct. Consumable cost per donor were below EUR 2.00. In
      routine use, 92.2% of samples were successfully predicted. Discrepancies were
      most frequently due to technical reasons. A total of 11 previously unknown
      alleles were detected in the Kell, Lutheran, and Colton blood group systems. In
      2017, more than 20% of the RBC units prepared by our institution were from donors
      with predicted antigen status. A steady supply of Yt(a-), Co(a-) and Lu(b-) RBC
      units was ensured. Conclusions: Pooled capillary electrophoresis offers a
      suitable alternative to other methods for extended donor DNA typing. Establishing
      a large cohort of typed donors improved transfusion support for patients.

PMID- 30283274
TI  - Rh-Matched Transfusion through Molecular Typing for beta-Thalassemia Patients Is
      Required and Feasible in Chinese.
AB  - Background: Molecular typing for RHCE blood group alleles has been established in
      many countries for patients and blood donors. In the Chinese literature nearly
      80% of transfused patients with alloimmunization have antibodies specific for
      antigens of the Rh blood group system. We investigated if it is feasible to match
      packed red blood cells (RBCs) for Chinese beta-thalassemia patients by RHCE
      genotyping. Methods: In this study, 481 patients with beta-thalassemia were
      enrolled. They were genotyped for RHCE alleles by a simple PCR method with
      sequence-specific primers (PCR-SSP). Among these patients, 203 continuously
      received RBCs of the identical Rh subgroups according to the genotyping results
      for at least 3 months. Subsequently, their phenotypes were tested through a micro
      column gel card method. For validation purposes, 400 donors were serologically
      typed with the same technology, of which 164 were genotyped too. Finally, the C,
      c, E, and e frequencies and the feasibility of the simple genotyping method were
      analyzed. Results: All patients showed mixed-field agglutination in the Rh
      subgroup gel cards before the same Rh subgroups in blood donors were selected for
      blood transfusion. The results, however, lacked mixed-field agglutination in all
      203 cases after transfusion with RBC concentrates selected for the patient's C,
      c, E, and e antigens for at least 3 months. The genotyping results of 164 donors
      were all consistent with the serological results. Whole coding regions of RHCE
      were sequenced in 7 individuals with weak c, E, or e antigens. In only one sample
      we observed a 1059G>A nucleotide mutation coding for a truncated RhCE polypeptide
      (GenBank KT957625), in the other 6 samples no sequence variant was found. Both
      patients and donors were predominantly CcEe and CCee, with a prevalence of 55.3%
      and 24.9% for patients or 49.3% and 31.3% for donors, respectively. It revealed
      that about 80% of Chinese could receive Rh-matched RBCs easily. Conclusion: A
      simple RHCE genotyping technique is safe enough for Rh-matched transfusion of
      beta-thalassemia patients in Chinese Han.

PMID- 30283273
TI  - Low-Frequency Blood Group Antigens in Switzerland.
AB  - Background: High-frequency blood group antigens (HFA) are present in >90% of the
      human population, according to some reports even in >99% of individuals.
      Therefore, patients lacking HFA may become challenging for transfusion support
      because compatible blood is hardly found, and if the patient carries
      alloantibodies, the cross-match will be positive with virtual every red cell unit
      tested. Methods: In this study, we applied high-throughput blood group SNP
      genotyping on >37,000 Swiss blood donors, intending to identify homozygous
      carriers of low-frequency blood group antigens (LFA). Results: 326 such
      individuals were identified and made available to transfusion specialists for
      future support of patients in need of rare blood products. Conclusion: Thorough
      comparison of minor allele frequencies using population genetics revealed
      heterogeneity of allele distributions among Swiss blood donors which may be
      explained by the topographical and cultural peculiarities of Switzerland.
      Moreover, geographically localized donor subpopulations are described which
      contain above-average numbers of individuals carrying rare blood group genotypes.

PMID- 30283275
TI  - Optimized Antigen-Matched in Sickle Cell Disease Patients: Chances and Challenges
      in Molecular Times - the Brazilian Way.
AB  - The development of red blood cell (RBC) alloantibodies and autoantibodies
      complicates transfusion therapy in sickle cell disease (SCD) patients. In an
      effort to reduce the risk of alloimmunization, some strategies have been used to
      provide antigen-matched RBC transfusions to patients with SCD in Brazil,
      including molecular matching in 3 levels: RH and K matching; extended matching
      (RH, KEL, FY, JK, MNS, DI), and extended matching including RHD and RHCE variant
      alleles. Molecular matching has shown clinical benefits to the patients with SCD,
      contributing significantly to reduce the rates of alloimmunization. Improvements
      in the clinical outcomes of the patients have also been observed as shown by an
      increase in their hemoglobin levels and reduction in their percentage of
      hemoglobin S as well as better in vivo RBC survival and diminished frequency of
      transfusions. However, prevention of RBC alloimmunization still remains a
      challenge in Brazil due to the difficulty to fulfill all transfusion requests of
      the patients with antigen-matching units, inaccuracy of RBC phenotyping, RBC
      transfusions outside the institution where the patient is treated, advanced age
      of some patients, the RBC antigen discrepancy between donors and recipients, and
      the presence of RH variants.

PMID- 30283276
TI  - Genotyping in Sickle Cell Disease Patients: The French Strategy.
AB  - This review presents the French strategy for blood group genotyping in high
      responder and newly diagnosed sickle cell disease (SCD) patients. In addition to
      FY, JK, and MNS genotyping, the RH blood group system is now explored in SCD
      patients in France. Molecular typing has been used for the deduction of partial
      RH2 (C) antigens since 2010, and the gradual implementation of systematic RHD and
      RHCE genotyping nationwide was initiated in late 2014. In our laboratory, 962
      RH:2 (C-positive) SCD patients have been tested since 2010, and 1,148 SCD
      patients of all RH phenotypes have been genotyped for clinically relevant alleles
      of RHD and RHCE since late 2014.

PMID- 30283277
TI  - Transfusion Support of Minority Patients: Extended Antigen Donor Typing and
      Recruitment of Minority Blood Donors.
AB  - One of the most important and persistent complications of blood transfusion is
      red blood cell (RBC) alloimmunization. When a patient is exposed to RBC antigens
      that differ from their own they can form alloantibodies to these foreign
      antigens. Blood group antigens are highly conserved and follow ancestral patterns
      of inheritance that may demonstrate population restriction. Minority populations
      who require chronic transfusion are at particularly high risk of alloimmunization
      when the blood donor population does not share the same ancestral background,
      resulting in exposure to non-self RBC antigens. It is incumbent on blood
      collectors to support patients with risk factors for alloimmunization as well as
      patients who have already formed alloantibodies. Increasing utilization of RBC
      genotyping may represent an opportunity to improve access to RBC units from
      donors that match the extended RBC phenotype of all possible patients.

PMID- 30283278
TI  - Multimodality Treatment of a Colorectal Cancer Stage IV Patient with FOLFOX-4,
      Bevacizumab, Rigvir Oncolytic Virus, and Surgery.
AB  - Colorectal cancer is one of the most commonly diagnosed cancers worldwide. The
      treatment consists of surgical resection, systemic chemotherapy, and new
      biological agents. One more recently emerging treatment option is oncolytic
      virotherapy. Although the use of the new treatment methods shows improved overall
      and progression-free survival, in general, even with the new treatments,
      mortality remains high and combinations of treatments should be sought to treat
      patients with colorectal cancer. Here we report a stage IV colorectal cancer
      patient who received multimodality treatment including bevacizumab, FOLFOX-4,
      surgery, and the oncolytic virus Rigvir. The patient shows complete pathological
      remission and remains stable 7.7 years after initial diagnosis. The possible
      benefits of combining Rigvir oncolytic virus and bevacizumab should be
      investigated since in vitro research suggests that anti-angiogenesis agents
      improve viral distribution by altering the microenvironment of the tumor.

PMID- 30283279
TI  - Glycogen Hepatopathy: A Rare and Underrecognized Cause of Recurrent Transaminitis
      in Patients with Uncontrolled Type 2 Diabetes Mellitus.
AB  - Glycogen hepatopathy (GH), characterized by reversible transaminitis and
      hepatomegaly, results from excessive accumulation of glycogen in hepatocytes. GH
      has been well described in the literature as a rare cause of transaminitis in
      children and young patients with uncontrolled type 1 diabetes mellitus and has
      rarely been reported in type 2 diabetic patients. Hyperglycemia and
      hyperinsulinemia are believed to be a metabolic substrate for hepatic glycogen
      accumulation and in order to cause glycogen hepatotoxicity. We present the case
      of a 54-year-old woman with poorly controlled insulin-dependent type 2 diabetes
      who was hospitalized twice within 1 month with diabetic ketoacidosis/hyperosmolar
      hyperglycemic state and reversible transaminitis. Interestingly, she had normal
      liver function tests performed at the time of admission and transaminitis was
      noted 1 day later, after she was treated with high doses of intravenous insulin
      therapy. Subsequently, liver enzymes recovered to normal levels with optimization
      of glucose control.

PMID- 30283281
TI  - Lethal Bleeding from a Duodenal Cancerous Ulcer Communicating with the Superior
      Mesenteric Artery in a Patient with Pancreatic Head Cancer.
AB  - Pancreatic cancer often invades the duodenum and causes obstruction, but rarely
      causes massive duodenal bleeding. A 68-year-old male was admitted to our hospital
      because of vomiting. Enhanced abdominal CT showed a hypovascular tumor with air
      bubbles in the uncinate process of the pancreas. The tumor invaded the duodenum
      and metastasized to the liver and peritoneum. The main trunk of the superior
      mesenteric artery (SMA) was circumferentially involved. After admission, he had
      hematemesis and melena. Emergency gastroduodenoscopy revealed pulsating vessels
      in the third portion of the duodenum and he eventually experienced hemorrhagic
      shock. Severe bleeding occurred from his mouth and anus like a catastrophic
      flood. It was difficult to sustain blood pressure even with massive blood
      transfusion with pumping. After insertion of an intra-aortic balloon occlusion
      catheter, the massive bleeding was eventually stopped. Although we attempted
      interventional radiography, aortography revealed direct communication between the
      main SMA trunk and the duodenal lumen. The tumor was considered anatomically and
      oncologically unresectable. Thus, we did not perform further intervention. The
      patient died 2 h after angiography. Herein, we report the case of pancreatic head
      cancer causing lethal bleeding associated with tumor-involved SMA. Duodenal
      bleeding associated with pancreatic cancer invasion should be considered as an
      oncogenic emergency.

PMID- 30283280
TI  - A Case of Gastroparesis after Cryoballoon Ablation followed by Medication-Induced
      Recovery within 6 Months.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia, and cryoballoon
      ablation was developed as a new treatment modality for symptomatic AF.
      Gastroparesis is rarely reported as a transient complication of ablation, and its
      frequency and risk are not clear. We experienced a rare case of gastroparesis
      after cryoballoon ablation followed by medication-induced recovery within 6
      months.

PMID- 30283282
TI  - A Young Adult Patient with Nonalcoholic Steatohepatitis Developed Severe
      Gastroesophageal Varices Associated with Severe Obesity and Diabetes Mellitus.
AB  - Obesity is a major contributor to insulin resistance and nonalcoholic fatty liver
      disease, which is the most common cause of chronic liver diseases. Nonalcoholic
      steatohepatitis (NASH) can progress to liver cirrhosis and end-stage liver
      diseases. Some cases already show severe liver fibrosis at the time of diagnosis.
      We present the case of a 44-year-old male with overt obesity who was admitted
      with hematemesis due to the rupture of gastric varices. We diagnosed him with
      NASH with severe liver fibrosis. This case shows that we should be concerned
      about the progression of liver fibrosis due to NASH associated with severe
      obesity even in young patients.

PMID- 30283283
TI  - Peroral Endoscopic Myotomy in Diffuse Thickened Esophageal Wall in an Adolescent.
AB  - Achalasia is an extremely rare pathology in children. Peroral endoscopic myotomy
      (POEM) is the gold standard for the surgical treatment of achalasia in adults,
      but only a limited number of cases of achalasia treatment using POEM in children
      have been published in the literature. Sometimes, high-resolution manometry signs
      of achalasia can mimic diffuse esophageal leiomyoma. This case report represents
      the first known successful performance of POEM on a 15-year-old female with
      diffuse thickening of the esophagus with signs and symptoms of achalasia and
      suspicion for Alport syndrome associated with diffuse esophageal leiomyoma.

PMID- 30283284
TI  - Simultaneous Resection for Synchronous Double Primary Cancers of the Pancreas and
      the Liver.
AB  - Simultaneous resection of synchronous hepatocellular carcinoma (HCC) and
      pancreatic ductal adenocarcinoma (PDAC) is extremely rare. Case 1 is a 64-year
      old woman, who had undergone anterior resection for rectal cancer 3 years earlier
      was pointed out to have a cystic tumor in the pancreatic tail and a solitary
      tumor in the liver. CT revealed a hypovascular tumor in the pancreatic tail and a
      liver tumor with early enhancement. With a diagnosis of simultaneous HCC and
      PDAC, she underwent laparotomy, in which intraoperative frozen section
      examination of the liver was compatible with HCC. Therefore, she underwent
      hepatic resection as well as distal pancreatectomy and splenectomy. The patient
      received adjuvant chemotherapy with S-1 and remains well with no evidence of
      tumor recurrence as of 28 months after resection. Case 2 is a 73-year-old man
      with sustained viral response to antiviral treatment for hepatitis C virus, who
      was pointed out to have a tumor in the pancreatic head and a solitary tumor in
      the liver. Gadoxetic acid-enhanced MRI exhibited enhancement compatible with HCC.
      With a diagnosis of concomitant HCC and PDAC, surgery was performed.
      Intraoperative frozen section examination was compatible with HCC, for which a
      pancreaticoduodenectomy was performed. The patient received adjuvant chemotherapy
      with S-1 and remains well with no evidence of tumor recurrence as of 16 months
      after resection. In conclusion, we describe 2 cases of hepato-pancreatectomy for
      synchronous double primary cancers of the pancreas and the liver, where exclusion
      of the liver tumor as a metastatic lesion from the pancreatic cancer is
      important.

PMID- 30283285
TI  - Arterial Pseudoaneurysm within a Pancreatic Pseudocyst.
AB  - The formation of pancreatic pseudocysts and (pseudo-)aneurysms of intestinal
      vessels are rare but life-threatening complications in acute and chronic
      pancreatitis. Here we report the rare case of a patient suffering from chronic
      pancreatitis with an arterial pseudoaneurysm within a pancreatic pseudocyst and
      present its successful therapeutic management by angioembolization to prevent
      critical bleeding. A 67-year-old male with a history of chronic pancreatitis
      presented with severe acute abdominal pain and vomiting to the emergency
      department. Seven weeks prior to the present admission, a CT scan had displayed a
      pancreatic pseudocyst with a maximum diameter of 53 mm. A laboratory examination
      revealed an elevated white blood cell count (15.40 * 103/MUL), as well as
      elevated serum lipase (191 U/L), bilirubin (1.48 mg/dL), and blood glucose (353
      mg/dL) levels. Sonographically, the previously described pancreatic pseudocyst
      revealed a slightly increased maximum diameter of 65 mm and an inhomogeneous echo
      of the cystic content. A contrast-enhanced CT scan showed a further increase in
      maximum diameter to 70 mm of the known pseudocyst. Inside the pseudocyst, a
      pseudoaneurysm originating from the splenic artery with a maximum diameter of 41
      mm was visualized. After interdisciplinary consultation, prophylactic coil
      embolization of the splenic artery was immediately performed. The pseudoaneurysm
      was shut off from blood supply by back-door/front-door occlusion employing 27
      coils, resulting in complete exclusion of the pseudoaneurysm from the
      circulation. Pseudoaneurysms are a rare complication of acute and chronic
      pancreatitis which has been shown to be efficiently treated by coil embolization.

PMID- 30283286
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1159/000486390.].

PMID- 30283287
TI  - Posterior Reversible Encephalopathy Syndrome following Ustekinumab Induction for
      Crohn's Disease.
AB  - Biological agents are frequently used in the management of inflammatory bowel
      disease, and it is important to understand the potential adverse effects of these
      therapies. Ustekinumab is a human monoclonal antibody that interferes with
      interleukin-12 and -23 cytokine signaling and is approved for the treatment of
      moderate to severe Crohn's disease. We report 2 cases of neurological adverse
      events, one of which is consistent with posterior reversible encephalopathy
      syndrome (PRES), in the setting of ustekinumab therapy for Crohn's disease. The
      first patient had a seizure and classic neuroimaging features of PRES following
      induction with ustekinumab. The second patient presented with acute
      encephalopathy and atypical imaging findings concerning for PRES after
      ustekinumab induction. Both patients recovered fully following cessation of
      ustekinumab therapy. PRES associated with ustekinumab is uncommon, but must be a
      consideration in Crohn's disease patients receiving this therapy who present with
      focal neurological symptoms or change in mentation.

PMID- 30283288
TI  - Jejunal Serrated Adenoma Diagnosed and Treated by Double-Balloon Enteroscopy.
AB  - Serrated polyps are most commonly located in the colorectum and have been well
      recognized as an important precursor lesion for colorectal cancer. Serrated
      adenoma in the small intestine has been reported more rarely but may represent a
      distinct morphological and biological subtype with malignant potential. Here, we
      present the case of a 65-year-old female who underwent double-balloon enteroscopy
      due to obscure gastrointestinal bleeding. A polyp sized 3.5 * 2.0 cm with a long
      pedicle in the jejunum, located 50 cm distal to the Treitz ligament, was
      detected. Endoscopic mucosal resection was done. The pathological results
      revealed a traditional serrated adenoma sized 3.5 * 2.2 cm.

PMID- 30283289
TI  - Long-Term Survival in Gastroesophageal Junction Adenocarcinoma: Ramucirumab.
AB  - We report a case of long-term survival with complete response of liver metastases
      within RAINBOW, a randomized, controlled trial of ramucirumab 8 mg/kg
      intravenously (days 1, 15) versus placebo, both plus paclitaxel 80 mg/m2
      intravenously (days 1, 8, 15), every 4 weeks in patients with previously treated
      advanced gastroesophageal junction adenocarcinoma. A 64-year-old man with
      gastroesophageal junction adenocarcinoma and liver metastases received first-line
      folinic acid, 5-fluorouracil plus oxaliplatin (FOLFOX) following jejunostomy. On
      liver progression, he enrolled in RAINBOW (April 2012), receiving ramucirumab. In
      November 2013, positron emission tomography scan was consistent with complete
      metabolic response, confirmed by a follow-up scan in March 2016.

PMID- 30283290
TI  - Successful Laparoscopy-Assisted Resection of the Descending Colon in a Patient
      with Multiple Large Renal Cysts and Stricture of the Colon due to Ischemic
      Colitis.
AB  - Large pathological structures in the abdominal cavity curb the application of
      laparoscopic surgery. This case report describes a successful laparoscopy
      assisted colectomy for benign colon disease in a patient with multiple large
      renal cysts. An 82-year-old man was referred to our department for treatment of
      stenosis of descending colon secondary to ischemic colitis. An abdominal computed
      tomography revealed multiple large renal cysts occupying a large proportion of
      the peritoneal cavity. To minimize the postoperative recovery period,
      laparoscopic surgery was planned despite the renal cysts. After inserting access
      ports, the walls of the several renal cysts were fenestrated with an electronic
      scalpel and the serous fluid was aspirated to enable continuation of the
      laparoscopic colectomy. The left colon was mobilized and extracted through an
      incision at the umbilicus, and the affected part of the colon was resected
      safely. The patient's postoperative course was uneventful, and the present case
      suggests that laparoscopy-assisted colectomy can be performed safely even in
      patients with multiple large renal cysts.

PMID- 30283291
TI  - Lorazepam as a Cause of Drug-Induced Liver Injury.
AB  - Lorazepam is a benzodiazepine derivative that is globally used for the therapy of
      anxiety and insomnia. A 51-year-old Japanese man with yellowish discoloration of
      the eyes and skin and pruritus was admitted due to liver dysfunction. He had
      taken lorazepam approximately 5 months prior to this admission. The clinical
      presentation and pathologic findings in the liver were consistent with drug
      induced liver injury. After cessation of lorazepam, treatment with Stronger neo
      minophagen C and ursodeoxycholic acid was started, and his liver injury resolved
      after 59 days. This case must serve as a warning to physicians to be aware of the
      possibility of unexpected liver injury caused by lorazepam.

PMID- 30283292
TI  - Melatonin Protects Against Neuronal Apoptosis via Suppression of the ATF6/CHOP
      Pathway in a Rat Model of Intracerebral Hemorrhage.
AB  - Neuronal apoptosis is an important factor accounting for the poor outcomes of
      intracerebral hemorrhage (ICH). This study first showed that inhibition of
      activating transcription factor 6 (ATF6) could alleviate secondary brain injury
      through anti-apoptosis after ICH in rats. Melatonin, ATF6 and CCAAT/enhancer
      binding protein homologous protein (CHOP) siRNAs were applied in this study.
      Brain edema, neurological functions, blood-brain barrier (BBB) integrity were
      evaluated at 24 h after ICH. Western blot analysis was used to evaluate the
      protein level of target proteins (ATF6, CHOP, Bip, Bcl-2, Bax, and cleaved
      caspase-3). Reverse transcription-polymerase chain reaction (RT-PCR) was used to
      assess the mRNA level of ATF6, CHOP and cleaved caspase-3. Terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and caspase
      3 immunofluorescence staining were applied to evaluate the neuronal cell death.
      The results suggested that the levels of ATF6 and its downstream protein, CHOP,
      were upregulated and reached the peak at 24 h after ICH. ATF6 was highly
      expressed in neurons. The administration of melatonin significantly decreased the
      mRNA and protein levels of ATF6, and its downstream targets, CHOP and cleaved
      caspase-3, but increased the Bcl-2/Bax ratio, which ameliorated the neurological
      functions. The CHOP siRNA significantly reversed the pro-apoptotic effect induced
      by the increased ATF6 level after ICH. Melatonin could protect against neuronal
      apoptosis via suppression of ATF6/CHOP arm of ER-stress-response pathway.

PMID- 30283293
TI  - Commentary: The Evolution of Musicality: What Can Be Learned from Language
      Evolution Research?

PMID- 30283294
TI  - Effects of Non-invasive Neuromodulation on Executive and Other Cognitive
      Functions in Addictive Disorders: A Systematic Review.
AB  - Background: In order to improve the current treatment of addictive disorders non
      invasive neuromodulation over the dorsolateral prefrontal cortex (DLPFC) has
      gained attention. The DLPFC is crucially involved in executive functioning,
      functions which are related to the course of addictive disorders. Non-invasive
      stimulation of the DLPFC may lead to changes in executive functioning. Currently
      an overview of effects of neuromodulation on these functions is lacking.
      Therefore, this systematic review addresses the effects of non-invasive
      neuromodulation on executive functioning in addictive disorders. Methods: The
      current review is conducted and reported in accordance with the Preferred
      Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015
      (PRISMA-P 2015) guidelines and has been registered in PROSPERO International
      Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero/,
      registration number: CRD42018084157). Original articles were searched using the
      Ovid MEDLINE, Embase and PsycINFO database. Results: The systematic search
      resulted in 1,228 unique studies, of which sixteen were included in the current
      review. Some of these studies do not address the classic definition of executive
      functions, but another cognitive function. However, they were included in this
      review since the field is small and still under development and we aim to give an
      inclusive overview in its broadest sense. The following executive and other
      cognitive functioning domains were assessed: attention, cognitive flexibility,
      response inhibition, memory and learning, problem solving, social cognition, risk
      taking, cognitive bias modification and overall executive functioning. The
      executive function domain most positively affected was social cognition followed
      by memory & learning, response inhibition, cognitive flexibility and attention.
      Conclusions: The studies addressed in the current review used a large variability
      of stimulation protocols and study designs which complicates comparability of the
      results. Nevertheless, the results of these studies are promising in light of
      improvement of current treatment. Therefore, we recommend future studies that
      compare the effect of different types of stimulation, stimulation sides and
      number of stimulation sessions in larger clinical trials. This will significantly
      increase the comparability of the studies and thereby accelerate and clarify the
      conclusion on whether non-invasive neuromodulation is an effective add-on
      treatment for substance dependence.

PMID- 30283296
TI  - Development and Characterization of PEDOT:PSS/Alginate Soft Microelectrodes for
      Application in Neuroprosthetics.
AB  - Reducing the mechanical mismatch between the stiffness of a neural implant and
      the softness of the neural tissue is still an open challenge in neuroprosthetics.
      The emergence of conductive hydrogels in the last few years has considerably
      widened the spectrum of possibilities to tackle this issue. Nevertheless, despite
      the advancements in this field, further improvements in the fabrication of
      conductive hydrogel-based electrodes are still required. In this work, we report
      the fabrication of a conductive hydrogel-based microelectrode array for neural
      recording using a hybrid material composed of poly(3,4-ethylenedioxythiophene)
      poly(styrenesulfonate), and alginate. The mechanical properties of the conductive
      hydrogel have been investigated using imaging techniques, while the electrode
      arrays have been electrochemically characterized at each fabrication step, and
      successfully validated both in vitro and in vivo. The presence of the conductive
      hydrogel, selectively electrodeposited onto the platinum microelectrodes, allowed
      achieving superior electrochemical characteristics, leading to a lower electrical
      noise during recordings. These findings represent an advancement in the design of
      soft conductive electrodes for neuroprosthetic applications.

PMID- 30283295
TI  - Fourier-Transform Infrared Imaging Spectroscopy and Laser Ablation -ICPMS New
      Vistas for Biochemical Analyses of Ischemic Stroke in Rat Brain.
AB  - Objective: Stroke is the main cause of adult disability in the world, leaving
      more than half of the patients dependent on daily assistance. Understanding the
      post-stroke biochemical and molecular changes are critical for patient survival
      and stroke management. The aim of this work was to investigate the photo
      thrombotic ischemic stroke in male rats with particular focus on biochemical and
      elemental changes in the primary stroke lesion in the somatosensory cortex and
      surrounding areas, including the corpus callosum. Materials and Methods: FT-IR
      imaging spectroscopy and LA-ICPMS techniques examined stroke brain samples, which
      were compared with standard immunohistochemistry studies. Results: The FTIR
      results revealed that in the lesioned gray matter the relative distribution of
      lipid, lipid acyl and protein contents decreased significantly. Also at this
      locus, there was a significant increase in aggregated protein as detected by high
      levels Abeta1-42. Areas close to the stroke focus experienced decrease in the
      lipid and lipid acyl contents associated with an increase in lipid ester, olefin,
      and methyl bio-contents with a novel finding of Abeta1-42 in the PL-GM and L-WM.
      Elemental analyses realized major changes in the different brain structures that
      may underscore functionality. Conclusion: In conclusion, FTIR bio-spectroscopy is
      a non-destructive, rapid, and a refined technique to characterize oxidative
      stress markers associated with lipid degradation and protein denaturation not
      characterized by routine approaches. This technique may expedite research into
      stroke and offer new approaches for neurodegenerative disorders. The results
      suggest that a good therapeutic strategy should include a mechanism that provides
      protective effect from brain swelling (edema) and neurotoxicity by scavenging the
      lipid peroxidation end products.

PMID- 30283297
TI  - The Contribution and Therapeutic Potential of Epigenetic Modifications in
      Alzheimer's Disease.
AB  - Alzheimer's disease is a progressive neurodegenerative disorder, affecting 50
      million people worldwide, for which there is no cure, or effective treatment.
      Individuals suffering from Alzheimer's show a decline in cognition over time
      beginning with memory loss and ultimately leading to severe dementia, and
      inability to care for themselves. The cause of Alzheimer's is not known but
      likely involves a combination of genetic, biochemical, and environmental factors.
      Some genes have been identified as risk factors but monozygotic twins discordant
      for Alzheimer's disease suggest other factors must contribute to development of
      the disease. Investigation on epigenetic marks including DNA methylation and post
      translational modifications of histones have shown that the patterns of these
      modifications change with age in the human population. Though individuals show
      specific differences in epigenetic marks at the individual gene level, there is a
      consistent pattern of epigenetic changes at the genome scale across the
      population. Similar changes have been identified in patients with Alzheimer's
      disease, though these occur at an earlier age compared to healthy individuals.
      The early cognitive impairment in Alzheimer's disease can be mistaken for
      premature ageing correlating with the timing of epigenetic changes occurring at a
      younger age in individuals with Alzheimer's. Such observations suggest that the
      epigenetic changes may contribute to disease pathology. Exactly how epigenetic
      modifications contribute to specific aspects of Alzheimer's disease is the focus
      of many researcher groups across the world. A number of drugs are available that
      inhibit the enzymes that modify chromatin and change the epigenetic landscape of
      the genome. Therefore, an understanding of the role of chromatin modifications in
      Alzheimer's could offer an opportunity for novel therapeutic strategies. Research
      using animal models of Alzheimer's suggests that the epigenetic changes in
      Alzheimer's disease may have a profound impact on cognition and underlie
      cognitive impairment while there is no clear evidence that they might contribute
      directly to neuronal loss.

PMID- 30283298
TI  - A Mitochondria-Associated Oxidative Stress Perspective on Huntington's Disease.
AB  - Huntington's disease (HD) is genetically caused by mutation of the Huntingtin
      (HTT) gene. At present, the mechanisms underlying the defect of HTT and the
      development of HD remain largely unclear. However, increasing evidence shows the
      presence of enhanced oxidative stress in HD patients. In this review article, we
      focus on the role of oxidative stress in the pathogenesis of HD and discuss
      mediators and potential mechanisms involved in mutant HTT-mediated oxidative
      stress generation and progression. Furthermore, we emphasize the role of the
      unicellular organism Saccharomyces cerevisiae in investigating mutant HTT-induced
      oxidative stress. Overall, this review article provides an overview of the latest
      findings regarding oxidative stress in HD and potential therapeutic targets for
      HD.

PMID- 30283299
TI  - Molecular Details of Retinal Guanylyl Cyclase 1/GCAP-2 Interaction.
AB  - The rod outer segment guanylyl cyclase 1 (ROS-GC1) is an essential component of
      photo-transduction in the retina. In the light-induced signal cascade, membrane
      bound ROS-GC1 restores cGMP levels in the dark in a calcium-dependent manner.
      With decreasing calcium concentration in the intracellular compartment, ROS-GC1
      is activated via the intracellular site by guanylyl cyclase-activating proteins
      (GCAP-1/-2). Presently, the exact activation mechanism is elusive. To obtain
      structural insights into the ROS-GC1 regulation by GCAP-2, chemical cross
      linking/mass spectrometry studies using GCAP-2 and three ROS-GC1 peptides were
      performed in the presence and absence of calcium. The majority of cross-links
      were identified with the C-terminal lobe of GCAP-2 and a peptide comprising parts
      of ROS-GC1's catalytic domain and C-terminal extension. Consistently with the
      cross-linking results, surface plasmon resonance and fluorescence measurements
      confirmed specific binding of this ROS-GC peptide to GCAP-2 with a dissociation
      constant in the low micromolar range. These results imply that a region of the
      catalytic domain of ROS-GC1 can participate in the interaction with GCAP-2.
      Additional binding surfaces upstream of the catalytic domain, in particular the
      juxtamembrane domain, can currently not be excluded.

PMID- 30283300
TI  - Peroxisome Proliferator Activated Receptor Agonists Modulate Transposable Element
      Expression in Brain and Liver.
AB  - Peroxisome proliferator activated receptors (PPARs) are nuclear hormone receptors
      that act as transcription factors in response to endogenous lipid messengers. The
      fibrates and thiazolidinediones are synthetic PPAR agonists used clinically to
      treat dyslipidemia and Type 2 Diabetes Mellitus, respectively, but also improve
      symptoms of several other diseases. Transposable elements (TEs), repetitive
      sequences in mammalian genomes, are implicated in many of the same conditions for
      which PPAR agonists are therapeutic, including neurodegeneration, schizophrenia,
      and drug addiction. We tested the hypothesis that there is a link between actions
      of PPAR agonists and TE expression. We developed an innovative application of
      microarray data by mapping Illumina mouse WG-6 microarray probes to areas of the
      mouse genome that contain TEs. Using this information, we assessed the effects of
      systemic administration of three PPAR agonists with different PPAR subtype
      selectivity: fenofibrate, tesaglitazar, and bezafibrate, on TE probe expression
      in mouse brain [prefrontal cortex (PFC) and amygdala] and liver. We found that
      fenofibrate, and bezafibrate to a lesser extent, up-regulated probes mapped to
      retrotransposons: Short-Interspersed Elements (SINEs) and Long-Interspersed
      Elements (LINEs), in the PFC. Conversely, all PPAR agonists down-regulated LINEs
      and tesaglitazar and bezafibrate also down-regulated SINEs in liver. We built
      gene coexpression networks that partitioned the diverse transcriptional response
      to PPAR agonists into groups of probes with highly correlated expression patterns
      (modules). Most of the differentially expressed retrotransposons were within the
      same module, suggesting coordinated regulation of their expression, possibly by
      PPAR signaling. One TE module was conserved across tissues and was enriched with
      genes whose products participate in epigenetic regulation, suggesting that PPAR
      agonists affect TE expression via epigenetic mechanisms. Other enriched
      functional categories included phenotypes related to embryonic development and
      learning and memory, suggesting functional links between these biological
      processes and TE expression. In summary, these findings suggest mechanistic
      relationships between retrotransposons and PPAR agonists and provide a basis for
      future exploration of their functional roles in brain and liver.

PMID- 30283302
TI  - The Effects of Chronic Stress on Migraine Relevant Phenotypes in Male Mice.
AB  - Migraine is a disabling neurological disorder affecting 12% of the world's
      population. Stress is a major reported trigger and exacerbator of migraine. We
      evaluated the effects of two chronic stress paradigms on migraine relevant
      phenotypes in male C57Bl/6 mice. Methods: Fifty six mice were used in a 14 day
      social defeat stress (SDS) and twenty three mice were used in a 40 day chronic
      variable stress (CVS) paradigm. Anxiety measures were evaluated using the open
      field and elevated plus maze (EPM) tests. Migraine relevant phenotypes were
      evaluated using the nitroglycerin (NTG) and cortical spreading depression (CSD)
      models. Results: Stress sensitive SDS mice and chronically stressed CVS mice
      showed decreased exploration in the open field and reduced time spent in the open
      arms of the EPM compared to controls. Stress sensitive and resilient SDS mice had
      increased serum corticosterone levels, and stressed mice in the CVS paradigm had
      decreased weight gain compared to controls, providing combined behavioral and
      physiological evidence of a stress response. In the CVS paradigm but not the SDS
      paradigm, the stressed group showed a significant decrease in baseline mechanical
      withdrawal threshold compared to controls. All groups showed a significant
      reduction in withdrawal threshold after treatment with NTG, but the reduction was
      not larger in SDS or CVS than in controls. Interestingly, stress resilient SDS
      mice showed a rapid recovery from NTG effects that was not seen in other groups.
      No difference in CSD frequency or velocity was seen between stress and control
      mice in either stress paradigms. Conclusion: We observed distinct effects of
      stress on generalized pain response, migraine relevant pain, and migraine
      relevant excitability. CVS but not SDS was associated with a reduced mechanical
      withdrawal threshold, consistent with a generalized pain response to chronic
      stress. Neither SDS nor CVS exacerbated phenotypes considered specifically
      relevant to migraine - withdrawal to NTG, and susceptibility to CSD. However, the
      significantly reduced response of stress resilient mice to the NTG stimulus may
      represent a specific migraine-resistant phenotype.

PMID- 30283301
TI  - Roles of Post-translational Modifications in Spinocerebellar Ataxias.
AB  - Post-translational modifications (PTMs), including phosphorylation, acetylation,
      ubiquitination, SUMOylation, etc., of proteins can modulate protein properties
      such as intracellular distribution, activity, stability, aggregation, and
      interactions. Therefore, PTMs are vital regulatory mechanisms for multiple
      cellular processes. Spinocerebellar ataxias (SCAs) are hereditary, heterogeneous,
      neurodegenerative diseases for which the primary manifestation involves ataxia.
      Because the pathogenesis of most SCAs is correlated with mutant proteins directly
      or indirectly, the PTMs of disease-related proteins might functionally affect SCA
      development and represent potential therapeutic interventions. Here, we review
      multiple PTMs related to disease-causing proteins in SCAs pathogenesis and their
      effects. Furthermore, we discuss these PTMs as potential targets for treating
      SCAs and describe translational therapies targeting PTMs that have been
      published.

PMID- 30283303
TI  - Putative Neural Network Within an Olfactory Sensory Unit for Nestmate and Non
      nestmate Discrimination in the Japanese Carpenter Ant: The Ultra-structures and
      Mathematical Simulation.
AB  - Ants are known to use a colony-specific blend of cuticular hydrocarbons (CHCs) as
      a pheromone to discriminate between nestmates and non-nestmates and the CHCs were
      sensed in the basiconic type of antennal sensilla (S. basiconica). To investigate
      the functional design of this type of antennal sensilla, we observed the ultra
      structures at 2D and 3D in the Japanese carpenter ant, Camponotus japonicus,
      using a serial block-face scanning electron microscope (SBF-SEM), and
      conventional and high-voltage transmission electron microscopes. Based on the
      serial images of 352 cross sections of SBF-SEM, we reconstructed a 3D model of
      the sensillum revealing that each S. basiconica houses > 100 unbranched dendritic
      processes, which extend from the same number of olfactory receptor neurons
      (ORNs). The dendritic processes had characteristic beaded-structures and formed a
      twisted bundle within the sensillum. At the "beads," the cell membranes of the
      processes were closely adjacent in the interdigitated profiles, suggesting
      functional interactions via gap junctions (GJs). Immunohistochemistry with anti
      innexin (invertebrate GJ protein) antisera revealed positive labeling in the
      antennae of C. japonicus. Innexin 3, one of the five antennal innexin subtypes,
      was detected as a dotted signal within the S. basiconica as a sensory organ for
      nestmate recognition. These morphological results suggest that ORNs form an
      electrical network via GJs between dendritic processes. We were unable to
      functionally certify the electric connections in an olfactory sensory unit
      comprising such multiple ORNs; however, with the aid of simulation of a
      mathematical model, we examined the putative function of this novel chemosensory
      information network, which possibly contributes to the distinct discrimination of
      colony-specific blends of CHCs or other odor detection.

PMID- 30283304
TI  - SK2 Channels Associate With mGlu1alpha Receptors and CaV2.1 Channels in Purkinje
      Cells.
AB  - The small-conductance, Ca2+-activated K+ (SK) channel subtype SK2 regulates the
      spike rate and firing frequency, as well as Ca2+ transients in Purkinje cells
      (PCs). To understand the molecular basis by which SK2 channels mediate these
      functions, we analyzed the exact location and densities of SK2 channels along the
      neuronal surface of the mouse cerebellar PCs using SDS-digested freeze-fracture
      replica labeling (SDS-FRL) of high sensitivity combined with quantitative
      analyses. Immunogold particles for SK2 were observed on post- and pre-synaptic
      compartments showing both scattered and clustered distribution patterns. We found
      an axo-somato-dendritic gradient of the SK2 particle density increasing 12-fold
      from soma to dendritic spines. Using two different immunogold approaches, we also
      found that SK2 immunoparticles were frequently adjacent to, but never overlap
      with, the postsynaptic density of excitatory synapses in PC spines. Co
      immunoprecipitation analysis demonstrated that SK2 channels form macromolecular
      complexes with two types of proteins that mobilize Ca2+: CaV2.1 channels and
      mGlu1alpha receptors in the cerebellum. Freeze-fracture replica double-labeling
      showed significant co-clustering of particles for SK2 with those for CaV2.1
      channels and mGlu1alpha receptors. SK2 channels were also detected at presynaptic
      sites, mostly at the presynaptic active zone (AZ), where they are close to CaV2.1
      channels, though they are not significantly co-clustered. These data demonstrate
      that SK2 channels located in different neuronal compartments can associate with
      distinct proteins mobilizing Ca2+, and suggest that the ultrastructural
      association of SK2 with CaV2.1 and mGlu1alpha provides the mechanism that ensures
      voltage (excitability) regulation by distinct intracellular Ca2+ transients in
      PCs.

PMID- 30283307
TI  - Brain Waves Evaluation of Sound Therapy in Chronic Subjective Tinnitus Cases
      Using Wavelet Decomposition.
AB  - Management and treatment of subjective tinnitus is an ongoing focus of research
      activities. One of the most viable assessments of such treatment is the
      evaluation of brain activity in addition to patient response and clinical
      assessment. This study focuses on sound therapy and evaluation of patients'
      electroencephalogram (EEG) in order to verify the potency of this approach.
      Broadband sound therapy was applied to nineteen participants aging from 25 to 64
      and suffering from chronic subjective tinnitus to study the difference of brain
      activity, a) before fake treatment, b) after fake treatment and c) after the main
      treatment, using EEG and Visual Analog Scale (VAS) for evaluating Residual
      Inhibition (RI). Four features were extracted using 4-level wavelet decomposition
      with Symlet 8 as its mother wavelet. For the "After the main treatment" stage,
      the mean value of wavelet coefficients for the last wavelet level, which
      corresponded to delta band of EEG, was lower in the FC3 channel based on Two
      Sample T-Test with significance level of 0.01, as compared to the same channel of
      the "before the treatment" stage, for cases in which decreased tinnitus loudness
      were reported.

PMID- 30283305
TI  - Gap Junctions in the Nervous System: Probing Functional Connections Using New
      Imaging Approaches.
AB  - Gap junctions are channels that physically connect adjacent cells, mediating the
      rapid exchange of small molecules, and playing an essential role in a wide range
      of physiological processes in nearly every system in the body, including the
      nervous system. Thus, altered function of gap junctions has been linked with a
      plethora of diseases and pathological conditions. Being able to measure and
      characterize the distribution, function, and regulation of gap junctions in
      intact tissue is therefore essential for understanding the physiological and
      pathophysiological roles that gap junctions play. In recent decades, several
      robust in vitro and in vivo methods have been developed for detecting and
      characterizing gap junctions. Here, we review the currently available methods
      with respect to invasiveness, signal-to-noise ratio, temporal resolution and
      others, highlighting the recently developed chemical tracers and hybrid imaging
      systems that use novel chemical compounds and/or genetically encoded enzymes,
      transporters, channels, and fluorescent proteins in order to map gap junctions.
      Finally, we discuss possible avenues for further improving existing techniques in
      order to achieve highly sensitive, cell type-specific, non-invasive measures of
      in vivo gap junction function with high throughput and high spatiotemporal
      resolution.

PMID- 30283306
TI  - Functional Anatomy of the Inferior Longitudinal Fasciculus: From Historical
      Reports to Current Hypotheses.
AB  - The inferior longitudinal fasciculus (ILF) is a long-range, associative white
      matter pathway that connects the occipital and temporal-occipital areas of the
      brain to the anterior temporal areas. In view of the ILF's anatomic connections,
      it has been suggested that this pathway has a major role in a relatively large
      array of brain functions. Until recently, however, the literature data on these
      potential functions were scarce. Here, we review the key findings of recent
      anatomic, neuromodulation, and neuropsychological studies. We also summarize
      reports on how this tract is disrupted in a wide range of brain disorders,
      including psychopathologic, neurodevelopmental, and neurologic diseases. Our
      review reveals that the ILF is a multilayered, bidirectional tract involved in
      processing and modulating visual cues and thus in visually guided decisions and
      behaviors. Accordingly, sudden disruption of the ILF by neurologic insult is
      mainly associated with neuropsychological impairments of visual cognition (e.g.,
      visual agnosia, prosopagnosia, and alexia). Furthermore, disruption of the ILF
      may constitute the pathophysiologic basis for visual hallucinations and socio
      emotional impairments in schizophrenia, as well as emotional difficulties in
      autism spectrum disorder. Degeneration of the ILF in neurodegenerative diseases
      affecting the temporal lobe may explain (at least in part) the gradual onset of
      semantic and lexical access difficulties. Although some of the functions mediated
      by the ILF appear to be relatively lateralized, observations from neurosurgery
      suggest that disruption of the tract's anterior portion can be dynamically
      compensated for by the contralateral portion. This might explain why bilateral
      disruption of the ILF in either acute or progressive disease is highly
      detrimental in neuropsychological terms.

PMID- 30283309
TI  - Ketamine Does Not Exert Protective Properties on Dopaminergic Neurons in the
      Lactacystin Mouse Model of Parkinson's Disease.
AB  - Parkinson's disease (PD) is an age-related neurodegenerative condition
      characterized by a progressive loss of dopaminergic neurons in the substantia
      nigra pars compacta (SNpc). A loss of proteasome function participates to the
      pathogenesis of PD, leading to the development of rodent models in which a
      proteasome inhibitor is applied to the nigrostriatal pathway. We recently
      characterized the intranigral lactacystin (LAC) mouse model, leading to
      nigrostriatal degeneration, motor dysfunction and alpha-synuclein accumulation.
      In the present study, we compared the effect of two commonly used anesthetics for
      generating animal models of PD-i.e., ketamine (KET) and isoflurane (ISO)-on the
      vulnerability of mouse dopaminergic neurons to proteasome inhibition-induced
      degeneration. Both anesthetics have the potential to affect the susceptibility of
      the nigrostriatal pathway for toxin-induced degeneration, and are known to
      modulate dopamine (DA) homeostasis. Yet, their impact on nigrostriatal
      degeneration in the proteasome inhibition model has not been evaluated.
      Unilateral injection with LAC in the SNpc of mice induced motor impairment and
      significantly reduced the number of dopaminergic cells to ~55%, irrespective of
      the anesthetic used. However, LAC-induced striatal DA depletion was slightly
      affected by the choice of anesthetic, resulting in a significant increase in DA
      turnover in the ISO- but not in KET-treated mice. These results suggest that the
      extent of nigrostriatal dopaminergic neural loss caused by LAC is not influenced
      by the choice of anesthetic, and that compared to other PD models, KET is not
      neuroprotective in the LAC model.

PMID- 30283308
TI  - Palatable Food Dampens the Long-Term Behavioral and Endocrine Effects of Juvenile
      Stressor Exposure but May Also Provoke Metabolic Syndrome in Rats.
AB  - The juvenile period is marked by a reorganization and growth of important brain
      regions including structures associating with reward seeking behaviors such as
      the nucleus accumbens (NA) and prefrontal cortex (PFC). These changes are
      impacted by stressors during the juvenile period and may lead to a predisposition
      to stress induced psychopathology and abnormal development of brain reward
      systems. Like in humans, adult rodents engage certain coping mechanisms such as
      increases in the consumption of calorie-rich palatable foods to reduce stress,
      but this behavior can lead to obesity and metabolic disorders. In this study, we
      examined whether stressors during the juvenile period led to increased caloric
      intake when a palatable diet was accessible, and whether this diet attenuated
      adult stress responses. In addition, we examined if the stress buffering effects
      produced by the palatable diet were also accompanied by an offset propensity
      towards obesity, and by alterations in mRNA expression of dopamine (DA) receptors
      in the NA and PFC in adulthood. To this end, juvenile male Wistar rats underwent
      episodic stressor exposure (forced swim, elevated platform stress and restraint)
      on postnatal days (PD) 27-29 and received access to regular chow or daily limited
      access to a palatable diet until adulthood. At the age of 2 months, rats were
      tested on a social interaction test that screens for anxiety-like behaviors and
      their endocrine responses to an acute stressor. Animals were sacrificed, and
      their brains processed to detect differences in DA receptor subtype expression in
      the PFC and NA using qPCR. Results showed that rats that were stressed during the
      juvenile period displayed higher social anxiety and a sensitized corticosterone
      response as adults and these effects were attenuated by access to the palatable
      diet. Nevertheless, rats that experienced juvenile stress and consumed a
      palatable diet showed greater adiposity in adulthood. Interestingly, the same
      group displayed greater mRNA expression of DA receptors at the NA. This suggests
      that access to a palatable diet mitigates the behavioral and endocrine effects of
      juvenile stressor exposure in adulthood, but at the cost of metabolic imbalances
      and a sensitized dopaminergic system.

PMID- 30283310
TI  - A State of Alcohol Hangover Impedes Everyday Prospective Memory.
AB  - The aim of the current study was to investigate what impact a state of alcohol
      hangover (AH) has upon everyday prospective memory (PM; memory for future
      events/intentions). Previous research has shown that the AH has a detrimental
      effect upon cognitive abilities, including memory and attentional deficits. No
      published research articles to date have focused upon what impact AH might have
      upon everyday memory, of which PM is a good example. The current study compared
      an AH group (AHG) with a non-hangover group (NHG) on PM. Since other drug use,
      anxiety and depression can affect PM independent of the AH, these covariates were
      controlled for in the study. Fifty-eight young adults studying at university
      participated in this between-subjects design study-25 in the AHG and 33 in the
      NHG. The Prospective Remembering Video Procedure (PRVP) measured PM. The Acute
      Hangover Rating Scale confirmed a state of AH and a Digital Breath Analyzer Test
      measured their BAC. The Hospital Anxiety and Depression Scale gauged levels of
      anxiety and depression and a Recreational Drug Use Questionnaire (RDUQ) measured
      alcohol and other drug use. Anyone who reported having used an illicit substance
      (e.g., cannabis, ecstasy) or who smoked, were excluded from the study. After
      controlling for age, alcohol units per week, years spent drinking alcohol,
      anxiety and depression scores, a one-way analysis of covariance (ANCOVA) revealed
      that the AHG (mean = 5.16) recalled significantly fewer items on the PRVP than
      the NHG (mean = 7.51)-F (1,52) = 5.69, p < 0.05. Overall, it appeared that a
      state of AH significantly impaired PM, which was not attributable to age, alcohol
      use, or anxiety or depression indices. Given the importance of PM to everyday
      activities, such as remembering to keep appointments or to take an important
      medication on time, this finding may have farther-reaching implications. These
      findings should also be used to educate young adults and health professionals
      dealing with the consequences with regards the dangers of alcohol misuse.

PMID- 30283311
TI  - Revisiting Inbred Mouse Models to Study the Developing Brain: The Potential Role
      of Intestinal Microbiota.

PMID- 30283312
TI  - Recurrent Granuloma Gluteale Infantum Secondary to Fecal Overflow Incontinence.
AB  - Granuloma gluteale infantum is a rare pediatric dermatological disorder of
      uncertain etiology. Suggested causes include fluorinated corticosteroids, Candida
      albicans, and irritant contact dermatitis. We present the case of a 3-year-old
      boy with recurrent episodes of granuloma gluteale infantum which resolved with
      treatment of his fecal overflow incontinence. As each recurrence correlated with
      a relapse of overflow incontinence, in this case the cause was irritant contact
      dermatitis from the liquid stool. This is the first reported case of recurrent
      granuloma gluteale infantum.

PMID- 30283313
TI  - A Case of Primary Cutaneous Basal Cell Carcinosarcoma.
AB  - A 94-year-old man consulted our hospital due to a rapidly growing tumor on the
      left cheek. The histological diagnosis of the tumor was basal cell
      carcinosarcoma, which was composed of intermingled epithelial and mesenchymal
      components. The former was basal cell carcinoma, while the latter was spindle
      cell sarcoma. The tumor was completely resected with a 3-mm margin and the
      patient remained free of local recurrence or distinct metastasis for 2 years. We
      report here a case of cutaneous basal cell carcinosarcoma and a review of the
      literature.

PMID- 30283314
TI  - Case Study of Onychomycosis Patients Treated with 1,064-nm Nd:YAG Laser.
AB  - Onychomycosis is the most frequent nail disease, with an estimated prevalence of
      2-8%. Current treatment strategies include the use of oral and topical
      antifungals, despite low cure rates following these treatments. The objectives of
      this study were to assess the therapeutic response of patients with onychomycosis
      to 1,064-nm Nd:YAG laser treatment, the clinical evaluation method available for
      this therapy, and the possible side effects of this treatment. Twenty patients
      with onychomycosis underwent laser therapy. A total of 34 nails with
      onychomycosis were assessed according to the Onychomycosis Severity Index (OSI).
      This index generates scores that classify onychomycosis as mild, moderate, or
      severe. The OSI was determined before treatment and after a mean follow-up period
      of 8 months. The comparison between the initial and the final OSI for all 34
      nails treated with laser therapy showed a significant difference; however, a low
      association was shown between these variables. A general reduction in the area of
      involvement and in the OSI numerical scores was observed. These data show a trend
      toward improvement in onychomycosis treated with 1,064-nm Nd:YAG laser. The OSI
      allowed an adequate clinical assessment of the response to laser therapy. Laser
      treatment did not cause marked discomfort in most patients, indicating that laser
      is a well-tolerated procedure.

PMID- 30283315
TI  - Hydrogen Sulfide and Hydrogen Sulfide-Synthesizing Enzymes Are Altered in a Case
      of Oral Adenoid Cystic Carcinoma.
AB  - Adenoid cystic carcinomas (ACC) constitute 1% of all head and neck malignancies
      and are very rare in the oral cavity. With < 60 oral ACCs described, their
      pathobiology is incompletely understood. Here, we report a case of oral cavity
      ACC in a 54-year-old woman. Since recent studies have demonstrated that several
      human tumors overexpress the hydrogen sulfide (H2S)-synthesizing enzymes
      cystathionine-beta-synthase (CBS), cystathionine gamma-lyase (CSE), and 3
      mercaptopyruvate sulfurtransferase (3-MST), and also show dysregulated H2S
      levels, we examined these biomarkers in the oral ACC and compared the results to
      those of adjacent benign oral epithelium. Western blotting was used to compare
      the protein expression of CBS, CSE, 3-MST, nicotinamide phosphoribosyl
      transferase, and mitoNEET in ACC and adjacent benign oral mucosae. High
      performance liquid chromatography was used to quantify the differences in tissue
      H2S concentrations between the two biopsy types. We found that all the proteins
      examined here were increased in the ACC compared to adjacent benign oral mucosae.
      Interestingly, H2S concentrations were decreased approximately 30% in ACC
      compared to benign mucosae. Thus, in one example of this rare tumor type, the
      enzymes that synthesize H2S are increased, while tissue H2S levels are lower than
      those found in adjacent benign oral mucosae. Although limited to a single rare
      tumor type, to our knowledge this is the second time H2S concentrations have been
      directly quantified inside a human tumor. Last, our results may indicate that
      alterations in H2S synthesis and metabolism may be important in the pathobiology
      of ACC.

PMID- 30283316
TI  - Extracranial Metastases of a Cerebral Glioblastoma: A Case Report and Review of
      the Literature.
AB  - The glioblastoma, a malignant human brain tumor, is known for its devastating
      intracranial progress and its dismal prognosis. Whereas treatment and research
      are most prominently focused on the primary tumor lesion, in recent years
      evidence has accumulated that points to the rare occurrence of extracranial
      glioblastoma metastases. We here present a case of a female patient with a known
      glioblastoma who was detected to harbor multiple metastases in the bones, lung,
      pleura, liver, mesentery, and the subcutaneous soft tissue. Pathogenetically,
      these metastatic lesions developed most probably after a local progression of the
      left temporal glioblastoma through the skull base, thus getting access to the
      systemic lymphatics. Similar cases of extensive glioblastoma metastization, their
      putative underlying mechanisms, and implications for clinical care are discussed.

PMID- 30283317
TI  - Two Cases of Long-Term Survival of Advanced Colorectal Cancer with Synchronous
      Lung Metastases Treated with mFOLFOX6/XELOX + Bevacizumab.
AB  - Background: Colorectal cancer (CRC) with lung metastases has an unfavorable
      prognosis. However, nowadays, even advanced CRC can have a favorable outcome in
      certain cases. A complete response (CR) is a rare event in advanced CRC with lung
      metastases. Herein, we report 2 rare cases of advanced CRC attaining a CR. Case
      Presentation: Case 1 was a 58-year-old man who underwent laparoscopic ileocecal
      resection for cecum cancer with multiple metastases to the lungs in 2011. We
      performed treatment with mFOLFOX6 and bevacizumab chemotherapy in August 2011.
      After 11 courses, computed tomography (CT) revealed a CR to chemotherapy in
      February 2012. He has remained disease-free for 5 years and 3 months. Case 2 was
      a 70-year-old woman who underwent laparoscopic ileocecal resection for cecum
      cancer in August 2010. Recurrence of multiple metastases to both lungs was
      detected in November 2010. We started treatment with XELOX and bevacizumab
      chemotherapy in January 2011. In January 2011, CT after 14 courses revealed
      disappearance of the lung lesions, thereby indicating a CR. She has remained
      disease-free for 5 years and 4 months. Conclusion: We encountered 2 patients with
      CRC with lung metastases who were treated with chemotherapy leading to a CR.
      Cases resulting in such a desirable outcome are extremely rare.

PMID- 30283318
TI  - Herniated Proximal Marker of the Stent into the Meningohypophyseal Trunk after
      Stent-Assisted Coil Embolization for Intracranial Aneurysms.
AB  - The SolitaireTM AB Neurovascular Remodeling Device (ev3, Irvine, CA, USA) is used
      to retain coils within an aneurysm, reducing the risk of embolic complications
      from coil herniation into the parent artery. Stents are deployed after confirming
      the optimal position of the stent markers across the aneurysm to avoid entry into
      perforators or branching arteries. Stent marker position is very important to
      prevent perforating or branching artery infarction. We performed stent-assisted
      coil embolization using the Solitaire AB stent to treat 2 aneurysms
      simultaneously. After successful coil embolization, we detached the Solitaire
      stent in the usual manner. However, the proximal stent marker, which was located
      at the horizontal segment of the cavernous internal carotid artery, moved into
      the meningohypophyseal trunk and occluded it. Although the distal markers were
      positioned optimally, we did not expect the proximal marker to be in the position
      where it was located. Fortunately, cranial nerve dysfunctions and pituitary
      deficiency did not develop. It is important to prevent ischemic injury by
      occlusion of the perforators or branching vessels that can be caused by
      malpositioned stent markers. We consider where the proximal marker of the stent
      might be located after detachment.

PMID- 30283319
TI  - A Fatal Case of Herpes Simplex Encephalitis with Two False-Negative Polymerase
      Chain Reactions.
AB  - An 88-year-old man presented with a 1-month history of altered mental status and
      seizures. His electrographic and imaging findings were suggestive of herpes
      simplex encephalitis (HSE), for which he was empirically treated with acyclovir.
      He underwent two lumbar punctures 3 days apart; both cerebrospinal fluid analyses
      tested negative for herpes simplex virus (HSV) by polymerase chain reaction
      (PCR). These negative results and his continued deterioration after 9 days of
      acyclovir therapy prompted treatment with steroids for possible autoimmune
      encephalitis. Shortly after the change in management, the patient died from
      cardiac arrest. At autopsy, his brain showed both gross and microscopic evidence
      of encephalitis and was positive for HSV by immunohistochemistry. This fatal case
      of HSE emphasizes the limitations of HSV PCR and the importance of clinical
      suspicion in the diagnosis and management of this disease.

PMID- 30283320
TI  - Low-Frequency rTMS and Intensive Occupational Therapy Improve Upper Limb Motor
      Function and Cortical Reorganization Assessed by Functional Near-Infrared
      Spectroscopy in a Subacute Stroke Patient.
AB  - There is still no agreement on the most suitable time and modality for
      application of repetitive transcranial magnetic stimulation (rTMS) to improve
      motor recovery in subacute stroke patients. The underlying mechanism of motor
      recovery following low-frequency rTMS is considered to be modulation of the
      interhemispheric asymmetry. On the other hand, the cortical balance of brain
      activity during the acute to chronic phase of stroke is reported to be unstable.
      Therefore, we conducted this study to clarify the time course of the
      interhemispheric asymmetry and the effect of application of low-frequency rTMS
      combined with occupational therapy on motor recovery and cortical imbalance of
      brain activity in a subacute stroke patient. The interhemispheric asymmetry in
      this patient with new-onset subcortical cerebral infarction and upper limb
      hemiparesis was evaluated longitudinally using functional near-infrared
      spectroscopy with finger tasks. A nonlesional hemisphere-dominant activation
      pattern was observed on day 28 after onset. On day 56 after onset, a bilaterally
      eminent activation pattern was observed. Low-frequency rTMS was applied on day
      109 after stroke onset when the cortical activity shifted to the nonlesional
      hemisphere. The treatment resulted in improvement in motor function of the
      affected upper limb and a shift in brain activation to the lesional hemisphere.
      Our report is the first to describe the therapeutic benefits of low-frequency
      rTMS as assessed by longitudinal neuroimaging for functional recovery and
      interhemispheric asymmetry in a subacute stroke patient.

PMID- 30283321
TI  - A Case of Nonalcoholic Marchiafava-Bignami Disease with Left-Right Differential
      Agraphia of Chinese Characters.
AB  - We report a 68-year-old right-handed female who was admitted to our hospital
      complaining chiefly of incontinence and decreased activity. Her brain images
      showed characteristics of Marchiafava-Bignami disease, such as symmetrical
      abnormal signals localized in the corpus callosum. The patient had no drinking
      habits. Her past medical history included total gastric resection to treat
      gastric cancer. On hospital admission she was markedly underweight. This appeared
      to be a rare case of Marchiafava-Bignami disease not attributable to heavy
      drinking and occurring in a state of malnutrition. Evaluation of callosal
      dissociation symptoms produced findings indicative of such symptoms. She showed a
      marked difficulty in writing dictated single words and short sentences in
      Japanese alphabetic characters, especially with her left hand. In contrast,
      writing dictated words in Chinese characters (also used in written Japanese) was
      affected in both hands, with different types of dysgraphia seen in the right and
      left hands. The agraphia in the left hand seen in this patient appears to have
      occurred as a result of the language faculty of the left hemisphere failing to be
      transmitted to the right brain, while agraphia in the right hand may have
      occurred as a result of spatial processing information in the right hemisphere
      failing to be transmitted to the left hemisphere.

PMID- 30283322
TI  - Effects of Long-Term Treatment with T-PEMF on Forearm Muscle Activation and Motor
      Function in Parkinson's Disease.
AB  - Bipolar pulsed electromagnetic stimulation applied to the brain (T-PEMF) is a non
      pharmacological treatment which has been shown to stimulate nerve growth,
      attenuate nerve abnormalities, and improve microcirculation. We report on a 62
      year-old, medically well-treated man with idiopathic Parkinson's disease. He was
      treated with T-PEMF, 30 min per day for three 8-week periods separated by two 1
      week breaks. The disease made his handwriting impossible to read mainly due to
      small letters and lack of fluency. Forearm EMG measured during standardized
      conditions showed an involuntary spiky EMG pattern with regular burst activity
      (on his left side) at baseline. The intervention normalized the handwriting and
      forearm EMG. The UPDRS-motor score decreased from 25 to 17, and UPDRS-II
      handwriting decreased from a pre-intervention value of 3 to 0 after the
      intervention. Finally, the patient reported improved fine motor function, less
      muscle stiffness, less muscle cramps and tingling, and less fatigue during the
      day in response to the T-PEMF treatment. The improved handwriting lasted for
      approximately 3 months after the treatment. Our results should be considered as
      preliminary, and large-scale, controlled studies are recommended to elucidate the
      therapeutic potential of long-term treatment with T-PEMF.

PMID- 30283323
TI  - An Autopsy Case of Edwardsiella tarda Meningoencephalitis.
AB  - A 62-year-old male with a history of alcohol abuse was admitted with a headache
      and rapidly progressing altered consciousness that led to coma over several
      hours. Blood and cerebrospinal fluid cultures were positive for Edwardsiella
      tarda. Despite prompt treatment initiation, the patient died on the third
      hospital day. Autopsy showed meningitis of the entire cerebrum with
      ventriculitis, and alcoholic fatty liver was observed. Clinicians should be
      cognizant of E. tarda meningoencephalitis, a rare presentation which can be
      associated with poor outcomes in patients with excessive alcohol consumption and
      alcoholic liver disease.

PMID- 30283324
TI  - A Case of Focal Choroidal Excavation Development Associated with Multiple
      Evanescent White Dot Syndrome.
AB  - Focal choroidal excavation (FCE) is described as an excavated lesion of the
      choroid that can be detected by optical coherence tomography (OCT). While the
      exact pathogenesis of FCE remains unclear, it has been proposed in some cases
      that there is an association with the inflammation in the outer retina. We
      present a case of FCE development that was detected by spectral domain OCT (SD
      OCT) and found to be associated with multiple evanescent white dot syndrome
      (MEWDS). A 40-year-old Japanese woman was diagnosed with MEWDS based on multiple
      white dots observed from the posterior pole to the midperiphery, along with
      yellow granularity in the fovea. SD-OCT revealed separation between the retinal
      pigment epithelium (RPE) and Bruch's membrane (BM) and discontinuations of the
      ellipsoid zone, RPE, and BM. At 4 weeks after onset, several of the white dots
      disappeared, the yellow granularity in the fovea became small, and we detected
      nonconforming choroidal excavation under the central fovea. The choroidal
      excavation gradually deepened and changed to a conforming pattern. These findings
      suggest that the degree of the impairment caused by inflammation and the
      plasticity of the BM and RPE complex may be associated with different types of
      acquired FCE.

PMID- 30283325
TI  - BrightOcular(r) Cosmetic Iris Implant: A Spectrum from Tolerability to Severe
      Morbidity.
AB  - Purpose: The BrightOcular(r) implants are the newest model of cosmetic iris
      devices that are currently advertised as safe. The previous generation known as
      NewColorIris(r) have had severe ocular side effects and were subsequently
      withdrawn from the market. There is little literature on the safety profile of
      BrightOcular(r) implants. Case Report: Herein we describe two cases with varying
      degrees of ocular tolerability. The first case had a normal ocular exam 1 year
      after implantation, whereas the second case had unilateral severe corneal edema
      requiring explantation of the iris device and Descemet membrane endothelial
      keratoplasty 9 months after bilateral implantation. Conclusions: These two cases
      attest to the unpredictability of the results of these cosmetic surgeries.
      Patients should be counseled about the vision-threatening complications of iris
      implants.

PMID- 30283326
TI  - A Case Report of Intravitreal Bevacizumab for Iris Metastasis of Small Cell Lung
      Carcinoma with Neovascular Glaucoma.
AB  - A 79-year-old man who had been diagnosed with small cell lung carcinoma (SCLC)
      complained of right ocular pain and blurred vision. His right intraocular
      pressure (IOP) was 30 mm Hg, and anterior chamber cells and multiple grayish
      white iris masses associated with peripheral anterior synechia (PAS) and
      neovascularization of the right iris were observed. We presumed that the iris
      masses were iris metastasis of SCLC. Despite therapy with topical eye drops and
      oral acetazolamide, the IOP was poorly controlled, so we injected intravitreal
      bevacizumab into his right eye for neovascular glaucoma. Neovascular glaucoma
      disappeared rapidly, but the IOP did not improve because of total PAS. To our
      knowledge, there is only one report of the use of intravitreal bevacizumab for
      SCLC metastasis in that eye and they reported that intravitreal injection
      resulted in successful short-term regression of presumed iris metastasis and
      improved control of secondary neovascular glaucoma, and the case had over one
      half PAS. The previous report and our results suggest that secondary neovascular
      glaucoma with iris metastasis may be controlled by early intravitreal bevacizumab
      injection.

PMID- 30283327
TI  - Case Series of Inappropriate Concentration of Intraocular Sulfur Hexafluoride.
AB  - Due to high complexity, vitreoretinal surgery presents a higher number of patient
      safety incidents compared with other ophthalmic procedures. Intraocular gases are
      one of the most useful adjuncts to vitrectomy and surprisingly, surgeons commonly
      admit to having occasional problems with incorrect gas concentration. The aim of
      this study is to present a consecutive case series of patients with improper
      concentration of sulfur hexafluoride (SF6) applied during vitrectomy. Three
      patients underwent 27-gauge vitrectomy and at the end of surgery inappropriate
      dilution of 100% SF6 was administered. It was attributed to a calculation error,
      change in the gas supplier, or increased partial pressure of SF6 before dilution.
      Postoperatively, due to IOP increase, two eyes required intravitreal gas-air
      exchange. Subsequently, cataract surgery was performed in one eye with
      concomitant vitrectomy and silicone oil tamponade due to retinal detachment. To
      prevent such complications, we suggest using intraocular gases with great care,
      training of ophthalmic personnel, and prompting manufacturers to provide SF6 in a
      prepared concentration of 20%.

PMID- 30283328
TI  - Blood in a Haab Stria.
AB  - We describe a case of an asymptomatic and spontaneous intracorneal hemorrhage in
      an adult with congenital glaucoma and blood collected in a Haab stria.

PMID- 30283329
TI  - Healthy Aging and Dementia: Two Roads Diverging in Midlife?
AB  - Dementia, particularly Alzheimer's disease (AD), is a growing pandemic that
      presents profound challenges to healthcare systems, families, and societies
      throughout the world. By 2050, the number of people living with dementia
      worldwide could almost triple, from 47 to 132 million, with associated costs
      rising to $3 trillion. To reduce the future incidence of dementia, there is an
      immediate need for interventions that target the disease process from its
      earliest stages. Research programs are increasingly starting to focus on midlife
      as a critical period for the beginning of AD-related pathology, yet the
      indicators of the incipient disease process in asymptomatic individuals remain
      poorly understood. We address this important knowledge gap by examining evidence
      for cognitive and structural brain changes that may differentiate, from midlife,
      healthy aging and pathological AD-related processes. This review crystallizes
      emerging trends for divergence between the two and highlights current limitations
      and opportunities for future research in this area.

PMID- 30283330
TI  - Clinical Heterogeneity Among LRRK2 Variants in Parkinson's Disease: A Meta
      Analysis.
AB  - Background: Parkinson's disease (PD) is one of the most common neurodegenerative
      diseases. Variants in the LRRK2 gene have been shown to be associated with PD.
      However, the clinical characteristics of LRRK2-related PD are heterogeneous. In
      our study, we performed a comprehensive pooled analysis of the association
      between specific LRRK2 variants and clinical features of PD. Methods: Articles
      from the Medline, Embase, and Cochrane databases were included in the meta
      analysis. Strict inclusion criteria were applied, and detailed information was
      extracted from the final original articles included. Revman 5.3 software was used
      for publication biases and pooled and sensitivity analyses. Results: In all, 66
      studies having the clinical manifestations of PD patients with G2019S, G2385R,
      R1628P, and R1441G were included for the final analysis. The prominent clinical
      features of LRRK2-G2019S-related PD patients were female sex, higher rates of
      early-onset PD (EOPD), and family history (OR: 0.77 [male], 1.37, 2.62; p <
      0.00001, 0.02, < 0.00001). PD patients with G2019S were more likely to have high
      scores of Schwab & England (MD: 1.49; p < 0.00001), low GDS scores, high UPSIT
      scores (MD: 0.43, 4.70; p = 0.01, < 0.00001), and good response to L-dopa (OR:
      2.33; p < 0.0001). Further, G2019S carriers had higher LEDD (MD: 115.20; p <
      0.00001) and were more likely to develop motor complications, such as dyskinesia
      and motor fluctuations (OR: 2.18, 2.02; p < 0.00001, 0.04) than non-carriers.
      G2385R carriers were more likely to have family history (OR: 2.10; p = 0.007)
      than non-G2385R carriers and lower H-Y and higher MMSE scores (MD: -0.13, 1.02; p
      = 0.02, 0.0007). G2385R carriers had higher LEDD and tended to develop motor
      complications, such as motor fluctuations (MD: 53.22, OR: 3.17; p = 0.01, <
      0.00001) than non-carriers. Other clinical presentations did not feature G2019S
      or G2385R. We observed no distinct clinical features for R1628P or R1441G. Our
      subgroup analyses in different ethnic group for specific variant also presented
      with relevant clinical characteristics of PD patients. Conclusions: Clinical
      heterogeneity was observed among LRRK2-associated PD in different variants in
      total and in different ethnic groups, especially for G2019S and G2385R.

PMID- 30283332
TI  - Investigation of the HSPG2 Gene in Tardive Dyskinesia - New Data and Meta
      Analysis.
AB  - Tardive dyskinesia (TD) is a movement disorder that may occur after extended use
      of antipsychotic medications. The etiopathophysiology is unclear; however,
      genetic factors play an important role. The Perlecan (HSPG2) gene was found to be
      significantly associated with TD in Japanese schizophrenia patients, and this
      association was subsequently replicated by an independent research group. To add
      to the evidence for this gene in TD, we conducted a meta-analysis specific to the
      relationship of HSPG2 rs2445142 with TD occurrence, while also adding our
      unpublished genotype data. Overall, we found a significant association of the G
      allele with TD occurrence (p = 0.0001); however, much of the effect appeared to
      originate from the discovery dataset. Nonetheless, most study samples exhibit the
      same trend of association with TD for the G allele. Our findings encourage
      further genetic and molecular studies of HSPG2 in TD.

PMID- 30283333
TI  - Prophylactic and Therapeutic Use of Strontium Ranelate Reduces the Progression of
      Experimental Osteoarthritis.
AB  - Introduction: Strontium ranelate (SrRan) has the potential to interfere in the
      progression of osteoarthritis (OA), multifactorial disease associated with
      mechanical problems and articular inflammatory changes. Objectives: This study
      aimed to test the effects of prophylactic and therapeutic use of SrRan on
      clinical parameters of pain, the inflammatory process, and degradation of the
      articular cartilage. Methods: This was an experimental study, using a model of
      knee OA induced by intra-articular injection of monoiodoacetate. Thirty Wistar
      rats were divided into five groups and treated as indicated: control, without
      intervention; prophylactic, received SrRan at a daily oral dose of 250 mg/kg for
      28 days before OA induction; SrRan treatments, administered 250 or 500 mg/kg/day
      for 28 days after the induction; and model control, received saline solution
      after the induction. Behavioral tests (joint incapacity, mechanical hyperalgesia,
      tactile sensitivity, and forced ambulation), histological evaluation of articular
      cartilage, and determination of inflammatory cytokines in the synovial fluid
      (interleukin [IL]-6, IL-10, tumor necrosis factor [TNF]-alpha, and interferon
      [INF]-gamma) were performed. Results: Both prophylactic and therapeutic
      treatments improved the articular discomfort. A prophylactic dose of 500
      mg/kg/day also improved mechanical hyperalgesia and the same dose was beneficial
      on tactile sensitivity. SrRan did not improve ambulation. Levels of IL-6, IL-10,
      TNF-alpha, and IFN-gamma in SrRan-treated groups with OA were not significantly
      different compared with those in the normal control animals. The
      histopathological evaluation showed less articular damage in the SrRan-treated
      and control groups compared to the saline-treated group. Conclusion: The
      prophylactic and therapeutic administration of SrRan was associated with improved
      behavioral patterns of pain, especially joint discomfort. SrRan administration
      mitigated histological changes in the articular cartilage and reduced the
      inflammatory process, which beneficially reduced the progression of OA in the
      experimental model studied.

PMID- 30283334
TI  - Bone Health and Natural Products- An Insight.
AB  - Bone metabolism involves a complex balance between matrix deposition,
      mineralization, and resorption. Numerous evidences have revealed that dietary
      components and phytoconstituents can influence these processes, through
      inhibition of bone resorption, thus exhibiting beneficial effects on the
      skeleton. Various traditional herbal formulae in ayurvedic and Chinese medicine
      have shown demonstrable benefits in pharmacological models of osteoporosis. The
      present review discusses normal bone metabolism and disorders caused by bone
      disruption, with particular reference to osteoporosis and current therapeutic
      treatment. Furthermore the effects of constituents from natural products on bone
      tissue are explained, with relevant evidences of efficacy in various experimental
      models.

PMID- 30283336
TI  - beta-Arrestin 2 Promotes Hepatocyte Apoptosis by Inhibiting Akt Pathway in
      Alcoholic Liver Disease.
AB  - Alcoholic liver disease (ALD) is a complex process that includes a wide range of
      hepatic lesions, from steatosis to cirrhosis, and even hepatocellular carcinoma
      (HCC). Accumulating evidence shows that the cytotoxic effects of ethanol
      metabolism lead to cell apoptosis and necrosis in ALD. Recently, several studies
      revealed that multifunctional protein beta-arrestin 2 (Arrb2) modulated cell
      apoptosis in liver fibrosis and HCC, but its role in ALD has not been fully
      understood. The aim of this study is to explore the function and underlying
      mechanism of Arrb2 in hepatocyte survival and apoptosis in ALD. In our study, the
      primary hepatocytes were isolated from the livers of C57BL/6 mice fed EtOH
      containing diet, it showed an increased level of Arrb2. EtOH also significantly
      up-regulated Arrb2 production in AML-12 cells in vitro. Furthermore, TUNEL
      (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) and FCM
      results demonstrated that knockdown of Arrb2 could inhibit hepatocyte apoptosis
      induced by EtOH in vivo and vitro while over-expression of Arrb2 induced
      apoptosis in ALD. In addition, western blot results revealed that Arrb2
      remarkably suppressed the Akt signaling. Taken together, our data suggested that
      Arrb2 may serve as a potential therapeutic target for ALD by promoting hepatocyte
      apoptosis via Akt suppression.

PMID- 30283337
TI  - The Modulatory Role of CYP3A4 in Dictamnine-Induced Hepatotoxicity.
AB  - Dictamni Cortex (DC) has been reported to be associated with acute hepatitis in
      clinic and may lead to a selective sub-chronic hepatotoxicity in rats.
      Nevertheless, the potent toxic ingredient and the underlying mechanism remain
      unknown. Dictamnine (DTN), the main alkaloid from DC, possesses a furan ring
      which was suspected of being responsible for hepatotoxicity via metabolic
      activation primarily by CYP3A4. Herein, the present study aimed to evaluate the
      role of CYP3A4 in DTN-induced liver injury. The in vitro results showed that the
      EC50 values in primary human hepatocytes (PHH), L02, HepG2 and NIH3T3 cells were
      correlated with the CYP3A4 expression levels in corresponding cells. Furthermore,
      the toxicity was increased in CYP3A4-induced PHH by rifampicin, and CYP3A4 over
      expressed (OE) HepG2 and L02 cells. Contrarily, the cytotoxicity was decreased in
      CYP3A4-inhibited PHH and CYP3A4 OE HepG2 and L02 cells inhibited by ketoconazole
      (KTZ). In addition, the hepatotoxicity of DTN in enzyme induction/inhibition mice
      was further investigated in the aspects of biochemistry, histopathology, and
      pharmacokinetics. Administration of DTN in combination with KTZ resulted in
      attenuated liver injury, including lower alanine transaminase and aspartate
      transaminase activities and greater AUC and C max of serum DTN, whereas,
      pretreatment with dexamethasone aggravated the injury. Collectively, our findings
      illustrated that DTN-induced hepatotoxicity correlated well with the expression
      of CYP3A4, namely inhibition of CYP3A4 alleviated the toxicity both in vitro and
      in vivo, and induction aggravated the toxicity effects.

PMID- 30283339
TI  - Urolithin A Inhibits the Catabolic Effect of TNFalpha on Nucleus Pulposus Cell
      and Alleviates Intervertebral Disc Degeneration in vivo.
AB  - Low back pain (LBP) is a common worldwide disease that causes an enormous social
      economic burden. Intervertebral disc degeneration (IDD) is considered as a major
      cause of LBP. The process of IDD is complicated and involves both inflammation
      and senescence. The production of pro-inflammatory cytokines, including tumor
      necrosis factor (TNF)alpha and interleukin (IL)-1beta, is increased in the
      degenerating intervertebral disc, inducing extracellular matrix degradation.
      Urolithin A (UA) is a metabolite compound resulting from the degradation of
      ellagitannins by gut bacteria. UA has been reported to be useful for the
      treatment of diseases associated with inflammation, senescence, and oxidative
      damage. Therefore, we hypothesized that UA may be an effective treatment for IDD.
      This study examined the effects of UA on IDD in vitro and in vivo and explored
      their underlying mechanisms. Our findings indicated that UA could attenuate
      cellular senescence induced by hydrogen peroxide in nucleus pulposus cells. UA
      treatment decreased TNFalpha-induced matrix metalloproteinase production and the
      loss of collagen II. At the molecular level, UA considerably blocked the
      phosphorylation of the extracellular signal-regulated kinase, c-JUN N-terminal
      kinase, and Akt pathways. In vivo study illustrated that UA treatment could
      ameliorate IDD in a needle-punctured rat tail model, which was evaluated by X-ray
      imaging, magnetic resonance imaging, and histological analysis. Thus, the results
      of our study revealed that UA may be a useful therapeutic agent for the treatment
      of IDD.

PMID- 30283338
TI  - Association of N6AMT1 rs2254638 Polymorphism With Clopidogrel Response in Chinese
      Patients With Coronary Artery Disease.
AB  - Dual antiplatelet treatment with aspirin and clopidogrel is the standard therapy
      for patients undergoing percutaneous coronary intervention (PCI). However, a
      portion of patients suffer from clopidogrel resistance (CR) and consequently with
      recurrence of cardiovascular events. Genetic factors such as loss-of-function
      variants of CYP2C19 contribute a lot to CR. Recently, the N-6-adenine-specific
      DNA methyltransferase 1 (N6AMT1) rs2254638 polymorphism is reported to be
      associated with clopidogrel response. To validate the association between N6AMT1
      rs2254638 polymorphism and clopidogrel response, 435 Chinese CAD patients
      receiving aspirin and clopidogrel were recruited. N6AMT1 rs2254638 and CYP2C19 *
      2/ * 3 polymorphisms were genotyped. Platelet reaction index (PRI) was measured
      by VASP-phosphorylation assay after treated with a 300 mg loading dose (LD)
      clopidogrel or 75 mg daily maintenance dose (MD) clopidogrel for at least 5 days.
      There was a significant difference in PRI between LD cohort and MD cohort.
      Carriers of CYP2C19 * 2 allele showed significantly increased PRI in the entire
      cohort and in respective of the MD and LD cohorts (p < 0.001, p = 0.003, p <
      0.001, respectively). However, carriers of CYP2C19 * 3 allele exhibited
      significantly higher PRI only in the entire cohort and LD cohort (p = 0.023, p =
      0.023 respectively). PRI value was significantly higher in CYP2C19 PM genotyped
      patients as compared with those carrying the IM genotypes and EM genotype (p <
      0.001). Besides, carriers of the rs2254638 C allele showed significantly higher
      PRI in entire cohort and in the LD cohort (p = 0.023, p = 0.008, respectively).
      When the patients were grouped into clopidogrel resistance (CR) and non
      clopidogrel resistance (non-CR) groups, CYP2C19 * 2 was associated with increased
      risk of CR in the entire cohort, the LD cohort and the MD cohort (p < 0.001, p <
      0.001, and p = 0.019, respectively). Carriers of the rs2254638 C allele also
      showed increased risk of CR in the entire cohort and the LD cohort (p = 0.024,
      and p = 0.028, respectively). N6AMT1 rs2254638 remained as a strong predictor for
      CR (TC vs. TT: OR = 1.880, 95% CI = 1.099-3.216,p = 0.021; CC vs. TT: OR = 1.930,
      95% CI = 1.056-3.527, p = 0.032; TC + CC vs. TT: OR = 1.846, 95%CI = 1.126-3.026,
      p = 0.015) after adjustment for confounding factors. Our study confirmed the
      influence of CYP2C19 *2 and rs2254638 polymorphisms on clopidogrel resistance in
      Chinese CAD patients. Both CYP2C19 * 2 and N6AMT1 rs2254638 polymorphism may
      serve as independent biomarkers to predict CR.

PMID- 30283340
TI  - Overexpression of MYCT1 Inhibits Proliferation and Induces Apoptosis in Human
      Acute Myeloid Leukemia HL-60 and KG-1a Cells in vitro and in vivo.
AB  - MYC target 1 (MYCT1), a direct target gene of c-Myc, is a novel candidate tumor
      suppressor gene first cloned from laryngeal squamous cell carcinoma. The
      downregulation of MYCT1 has been reported to be associated with carcinogenesis.
      However, the role of MYCT1 in the development and progress of acute myeloid
      leukemia (AML) remains unknown and requires further investigation. In this study,
      we first found that the expression level of MYCT1 was significantly lower in the
      bone marrow (BM) derived from AML patients than that from healthy individuals.
      The low expression of MYCT1 in AML BM may be due to the hypermethylation in its
      promoter. MYCT1 expression was strongly associated with French-American-British
      classifications of AML. The low expression level of MYCT1 was more often observed
      in patients of M1, M5 and M6 types. In vitro, lentiviral particles carrying the
      complete CDS of MYCT1 gene were used to mediate the forced overexpression of
      MYCT1 in two AML cell lines, HL-60 and KG-1a. MYCT1 overexpression significantly
      inhibited cell proliferation, arrested cell cycle at G0/G1 phase, and
      downregulated the expression of cyclins D and E. Moreover, MYCT1 overexpression
      triggered apoptosis in AML cells, which was accompanied by enhanced cleavage of
      caspase-3 and -9, upregulated expression of B-cell lymphoma 2 (Bcl-2)-associated
      X protein (Bax), and downregulated Bcl-2. Finally, in BALB/c nude mice bearing
      xenograft tumors generated by HL-60 and KG-1a cells, we noted that the
      intratumoral injection of MYCT1 lentivirus repressed tumor growth and led to
      massive apoptosis. In summary, our results reveal that MYCT1's promoter is
      hypermethylated and its expression is downregulated in the BM of AML patients.
      MYCT1 plays a tumor-suppressive role, and it may serve as a promising target for
      the genetic therapeutic strategy in treating AML.

PMID- 30283335
TI  - Development of an AmpliSeqTM Panel for Next-Generation Sequencing of a Set of
      Genetic Predictors of Persisting Pain.
AB  - Background: Many gene variants modulate the individual perception of pain and
      possibly also its persistence. The limited selection of single functional
      variants is increasingly being replaced by analyses of the full coding and
      regulatory sequences of pain-relevant genes accessible by means of next
      generation sequencing (NGS). Methods: An NGS panel was created for a set of 77
      human genes selected following different lines of evidence supporting their role
      in persisting pain. To address the role of these candidate genes, we established
      a sequencing assay based on a custom AmpliSeqTM panel to assess the exomic
      sequences in 72 subjects of Caucasian ethnicity. To identify the systems biology
      of the genes, the biological functions associated with these genes were assessed
      by means of a computational over-representation analysis. Results: Sequencing
      generated a median of 2.85 ? 106 reads per run with a mean depth close to 200
      reads, mean read length of 205 called bases and an average chip loading of 71%. A
      total of 3,185 genetic variants were called. A computational functional genomics
      analysis indicated that the proposed NGS gene panel covers biological processes
      identified previously as characterizing the functional genomics of persisting
      pain. Conclusion: Results of the NGS assay suggested that the produced nucleotide
      sequences are comparable to those earned with the classical Sanger sequencing
      technique. The assay is applicable for small to large-scale experimental setups
      to target the accessing of information about any nucleotide within the addressed
      genes in a study cohort.

PMID- 30283341
TI  - Electrical Spinal Stimulation, and Imagining of Lower Limb Movements to Modulate
      Brain-Spinal Connectomes That Control Locomotor-Like Behavior.
AB  - Neuronal control of stepping movement in healthy human is based on integration
      between brain, spinal neuronal networks, and sensory signals. It is generally
      recognized that there are continuously occurring adjustments in the physiological
      states of supraspinal centers during all routines movements. For example, visual
      as well as all other sources of information regarding the subject's environment.
      These multimodal inputs to the brain normally play an important role in providing
      a feedforward source of control. We propose that the brain routinely uses these
      continuously updated assessments of the environment to provide additional
      feedforward messages to the spinal networks, which provides a synergistic
      feedforwardness for the brain and spinal cord. We tested this hypothesis in 8 non
      injured individuals placed in gravity neutral position with the lower limbs
      extended beyond the edge of the table, but supported vertically, to facilitate
      rhythmic stepping. The experiment was performed while visualizing on the monitor
      a stick figure mimicking bilateral stepping or being motionless. Non-invasive
      electrical stimulation was used to neuromodulate a wide range of excitabilities
      of the lumbosacral spinal segments that would trigger rhythmic stepping
      movements. We observed that at the same intensity level of transcutaneous
      electrical spinal cord stimulation (tSCS), the presence or absence of visualizing
      a stepping-like movement of a stick figure immediately initiated or terminated
      the tSCS-induced rhythmic stepping motion, respectively. We also demonstrated
      that during both voluntary and imagined stepping, the motor potentials in leg
      muscles were facilitated when evoked cortically, using transcranial magnetic
      stimulation (TMS), and inhibited when evoked spinally, using tSCS. These data
      suggest that the ongoing assessment of the environment within the supraspinal
      centers that play a role in planning a movement can routinely modulate the
      physiological state of spinal networks that further facilitates a synergistic
      neuromodulation of the brain and spinal cord in preparing for movements.

PMID- 30283342
TI  - Theoretical Explorations Generate New Hypotheses About the Role of the Cartilage
      Endplate in Early Intervertebral Disk Degeneration.
AB  - Altered cell nutrition in the intervertebral disk (IVD) is considered a main
      cause for disk degeneration (DD). The cartilage endplate (CEP) provides a major
      path for the diffusion of nutrients from the peripheral vasculature to the IVD
      nucleus pulposus (NP). In DD, sclerosis of the adjacent bony endplate is
      suggested to be responsible for decreased diffusion and disk cell nutrition. Yet,
      experimental evidence does not support this hypothesis. Hence, we evaluated how
      moderate CEP composition changes related to tissue degeneration can affect disk
      nutrition and cell viability. A novel composition-based permeability formulation
      was developed for the CEP, calibrated, validated, and used in a mechano-transport
      finite element IVD model. Fixed solute concentrations were applied at the outer
      surface of the annulus and the CEP, and three cycles of daily mechanical load
      were simulated. The CEP model indicated that CEP permeability increases with the
      degeneration/aging of the tissue, in accordance with recent measurements reported
      in the literature. Additionally, our results showed that CEP degeneration might
      be responsible for mechanical load-induced NP dehydration, which locally affects
      oxygen and lactate levels, and reduced glucose concentration by 16% in the NP
      annulus transition zone. Remarkably, CEP degeneration was a condition sine-qua
      non to provoke cell starvation and death, while simulating the effect of
      extracellular matrix depletion in DD. This theoretical study cast doubts about
      the paradigm that CEP calcification is needed to provoke cell starvation, and
      suggests an alternative path for DD whereby the early degradation of the CEP
      plays a key role.

PMID- 30283331
TI  - Intracrine Regulation of Estrogen and Other Sex Steroid Levels in Endometrium and
      Non-gynecological Tissues; Pathology, Physiology, and Drug Discovery.
AB  - Our understanding of the intracrine (or local) regulation of estrogen and other
      steroid synthesis and degradation expanded in the last decades, also thanks to
      recent technological advances in chromatography mass-spectrometry. Estrogen
      responsive tissues and organs are not passive receivers of the pool of steroids
      present in the blood but they can actively modify the intra-tissue steroid
      concentrations. This allows fine-tuning the exposure of responsive tissues and
      organs to estrogens and other steroids in order to best respond to the
      physiological needs of each specific organ. Deviations in such intracrine control
      can lead to unbalanced steroid hormone exposure and disturbances. Through a
      systematic bibliographic search on the expression of the intracrine enzymes in
      various tissues, this review gives an up-to-date view of the intracrine estrogen
      metabolisms, and to a lesser extent that of progestogens and androgens, in the
      lower female genital tract, including the physiological control of endometrial
      functions, receptivity, menopausal status and related pathological conditions. An
      overview of the intracrine regulation in extra gynecological tissues such as the
      lungs, gastrointestinal tract, brain, colon and bone is given. Current
      therapeutic approaches aimed at interfering with these metabolisms and future
      perspectives are discussed.

PMID- 30283344
TI  - Impact of Intrauterine Growth Restriction on Cognitive and Motor Development at 2
      Years of Age.
AB  - Intrauterine growth restriction (IUGR), which is already known to be a risk
      factor for pathological intrauterine development, perinatal mortality, and
      morbidity, is now also assumed to cause both physical and cognitive alterations
      in later child development. In the current study, effects of IUGR on infantile
      brain function were investigated during the fetal period and in a follow-up
      developmental assessment during early childhood. During the fetal period, visual
      and auditory event-related responses (VER and AER) were recorded using fetal
      magnetoencephalography (fMEG). VER latencies were analyzed in 73 fetuses (14 IUGR
      fetuses) while AER latencies were analyzed in 66 fetuses (11 IUGR fetuses).
      Bayley Scales of Infant Development, Second Edition (BSID-II) were used to assess
      the developmental status of the infants at the age of 24 months. The Mental
      Development Index (MDI) was available from 66 children (8 IUGR fetuses) and the
      Psychomotor Development Index (PDI) from 63 children (7 IUGR fetuses). Latencies
      to visual stimulation were more delayed in IUGR than in small for gestational age
      (SGA) or appropriate for gestational age (AGA) fetuses, albeit not to any
      significant extent (p = 0.282). The MDI in former IUGR infants was significantly
      lower (p = 0.044) than in former SGA and AGA infants. However, IUGR had no impact
      on PDI (p = 0.213). These findings support the hypothesis that IUGR may
      constitute a risk factor for neurodevelopmental delay. Further investigation of
      the possible underlying mechanisms, as well as continued long-term developmental
      research, is therefore necessary.

PMID- 30283343
TI  - The Role of Calcitonin Gene Related Peptide (CGRP) in Neurogenic Vasodilation and
      Its Cardioprotective Effects.
AB  - Calcitonin gene-related peptide (CGRP) is a highly potent vasoactive peptide
      released from sensory nerves, which is now proposed to have protective effects in
      several cardiovascular diseases. The major alpha-form is produced from alternate
      splicing and processing of the calcitonin gene. The CGRP receptor is a complex
      composed of calcitonin like receptor (CLR) and a single transmembrane protein,
      RAMP1. CGRP is a potent vasodilator and proposed to have protective effects in
      several cardiovascular diseases. CGRP has a proven role in migraine and selective
      antagonists and antibodies are now reaching the clinic for treatment of migraine.
      These clinical trials with antagonists and antibodies indicate that CGRP does not
      play an obvious role in the physiological control of human blood pressure. This
      review discusses the vasodilator and hypotensive effects of CGRP and the role of
      CGRP in mediating cardioprotective effects in various cardiovascular models and
      disorders. In models of hypertension, CGRP protects against the onset and
      progression of hypertensive states by potentially counteracting against the pro
      hypertensive systems such as the renin-angiotensin-aldosterone system (RAAS) and
      the sympathetic system. With regards to its cardioprotective effects in
      conditions such as heart failure and ischaemia, CGRP-containing nerves innervate
      throughout cardiac tissue and the vasculature, where evidence shows this peptide
      alleviates various aspects of their pathophysiology, including cardiac
      hypertrophy, reperfusion injury, cardiac inflammation, and apoptosis. Hence, CGRP
      has been suggested as a cardioprotective, endogenous mediator released under
      stress to help preserve cardiovascular function. With the recent developments of
      various CGRP-targeted pharmacotherapies, in the form of CGRP
      antibodies/antagonists as well as a CGRP analog, this review provides a summary
      and a discussion of the most recent basic science and clinical findings,
      initiating a discussion on the future of CGRP as a novel target in various
      cardiovascular diseases.

PMID- 30283346
TI  - Carotid Body Type-I Cells Under Chronic Sustained Hypoxia: Focus on Metabolism
      and Membrane Excitability.
AB  - Chronic sustained hypoxia (CSH) evokes ventilatory acclimatization characterized
      by a progressive hyperventilation due to a potentiation of the carotid body (CB)
      chemosensory response to hypoxia. The transduction of the hypoxic stimulus in the
      CB begins with the inhibition of K+ currents in the chemosensory (type-I) cells,
      which in turn leads to membrane depolarization, Ca2+ entry and the subsequent
      release of one- or more-excitatory neurotransmitters. Several studies have shown
      that CSH modifies both the level of transmitters and chemoreceptor cell
      metabolism within the CB. Most of these studies have been focused on the role
      played by such putative transmitters and modulators of CB chemoreception, but
      less is known about the effect of CSH on metabolism and membrane excitability of
      type-I cells. In this mini-review, we will examine the effects of CSH on the ion
      channels activity and excitability of type-I cell, with a particular focus on the
      effects of CSH on the TASK-like background K+ channel. We propose that changes on
      TASK-like channel activity induced by CSH may contribute to explain the
      potentiation of CB chemosensory activity.

PMID- 30283345
TI  - The Role of Neuropeptide Y in Cardiovascular Health and Disease.
AB  - Neuropeptide Y (NPY) is an abundant sympathetic co-transmitter, widely found in
      the central and peripheral nervous systems and with diverse roles in multiple
      physiological processes. In the cardiovascular system it is found in neurons
      supplying the vasculature, cardiomyocytes and endocardium, and is involved in
      physiological processes including vasoconstriction, cardiac remodeling, and
      angiogenesis. It is increasingly also implicated in cardiovascular disease
      pathogenesis, including hypertension, atherosclerosis, ischemia/infarction,
      arrhythmia, and heart failure. This review will focus on the physiological and
      pathogenic role of NPY in the cardiovascular system. After summarizing the NPY
      receptors which predominantly mediate cardiovascular actions, along with their
      signaling pathways, individual disease processes will be considered. A thorough
      understanding of these roles may allow therapeutic targeting of NPY and its
      receptors.

PMID- 30283348
TI  - Energy Expenditure as a Function of Activity Level After Spinal Cord Injury: The
      Need for Tetraplegia-Specific Energy Balance Guidelines.
AB  - The World Health Organization recognizes obesity as a global and increasing
      problem for the general population. Because of their reduced physical
      functioning, people with spinal cord injury (SCI) face additional challenges for
      maintaining an appropriate whole body energy balance, and the majority with SCI
      are overweight or obese. SCI also reduces exercise capacity, particularly in
      those with higher-level injury (tetraplegia). Tetraplegia-specific caloric energy
      expenditure (EE) data is scarce. Therefore, we measured resting and exercise
      based energy expenditure in participants with tetraplegia and explored the
      accuracy of general population-based energy use predictors. Body composition and
      resting energy expenditure (REE) were measured in 25 adults with tetraplegia
      (C4/5 to C8) and in a sex-age-height matched group. Oxygen uptake, carbon dioxide
      production, heart rate, perceived exertion, and exercise intensity were also
      measured in 125 steady state exercise trials. Those with motor-complete
      tetraplegia, but not controls, had measured REE lower than predicted (mean = 22%
      less, p < 0.0001). REE was also lower than controls when expressed per kilogram
      of lean mass. Nine had REE below 1200 kcal/day. We developed a graphic compendium
      of steady state EE during arm ergometry, wheeling, and hand-cycling. This
      compendium is in a format that can be used by persons with tetraplegia for
      exercise prescription (calories, at known absolute intensities). EE was low (55
      450 kcal/h) at the intensities participants with tetraplegia were capable of
      maintaining. If people with tetraplegia followed SCI-specific activity guidelines
      (220 min/week) at the median intensities we measured, they would expend 563-1031
      kcal/week. Participants with tetraplegia would therefore require significant time
      (4 to over 20 h) to meet a weekly 2000 kcal exercise target. We estimated total
      daily EE for a range of activity levels in tetraplegia and compared them to
      predicted values for the general population. Our analysis indicated that the EE
      values for sedentary through moderate levels of activity in tetraplegia fall well
      below predicted sedentary levels of activity for the general population. These
      findings help explain sub-optimal responses to exercise interventions after
      tetraplegia, and support the need to develop tetraplegia-specific energy-balance
      guidelines that reflects their unique EE situation.

PMID- 30283349
TI  - Effects of 3 Weeks of Oral Low-Dose Cobalt on Hemoglobin Mass and Aerobic
      Performance.
AB  - Introduction: Cobalt ions (Co2+) stabilize HIFalpha and increase endogenous
      erythropoietin (EPO) production creating the possibility that Co2+ supplements
      (CoSupp) may be used as performance enhancing substances. The aim of this study
      was to determine the effects of a small oral dosage of CoSupp on hemoglobin mass
      (Hbmass) and performance with the objective of providing the basis for
      establishing upper threshold limits of urine [Co2+] to detect CoSupp misuse in
      sport. Methods: Twenty-four male subjects participated in a double-blind placebo
      controlled study. Sixteen received an oral dose of 5 mg of ionized Co2+ per day
      for 3 weeks, and eight served as controls. Blood and urine samples were taken
      before the study, during the study and up to 3 weeks after CoSupp. Hbmass was
      determined by the CO-rebreathing method at regular time intervals, and VO2max was
      determined before and after the CoSupp administration period. Results: In the
      Co2+ group, Hbmass increased by 2.0 +/- 2.1% (p < 0.001) while all the other
      analyzed hematological parameters did not show significant interactions of time
      and treatment. Hemoglobin concentration ([Hb]) and hematocrit (Hct) tended to
      increase (p = 0.16, p = 0.1) and also [EPO] showed a similar trend (baseline: 9.5
      +/- 3.0, after 2 weeks: 12.4 +/- 5.2 mU/ml). While mean VO2max did not change,
      there was a trend for a positive relationship between changes in Hbmass and
      changes in VO2max immediately after CoSupp (r = 0.40, p = 0.11). Urine [Co2+]
      increased from 0.4 +/- 0.3 to 471.4 +/- 384.1 ng/ml (p < 0.01) and remained
      significantly elevated until 2 weeks after cessation. Conclusion: An oral Co2+
      dosage of 5 mg/day for 3 weeks effectively increases Hbmass with a tendency to
      increase hemoglobin concentration ([Hb]) and hematocrit (Hct). Because urine Co2+
      concentration remains increased for 2 weeks after cessation, upper limit
      threshold values for monitoring CoSupp can be established.

PMID- 30283347
TI  - Fatigue in Chronic Respiratory Diseases: Theoretical Framework and Implications
      For Real-Life Performance and Rehabilitation.
AB  - Fatigue is a primary disabling symptom in chronic respiratory diseases (CRD) with
      major clinical implications. However, fatigue is not yet sufficiently explored
      and is still poorly understood in CRD, making this symptom underdiagnosed and
      undertreated in these populations. Fatigue is a dynamic phenomenon, particularly
      in such evolving diseases punctuated by acute events which can, alone or in
      combination, modulate the degree of fatigue experienced by the patients. This
      review supports a comprehensive inter-disciplinary approach of CRD-related
      fatigue and emphasizes the need to consider both its performance and perceived
      components. Most studies in CRD evaluated perceived fatigue as a trait
      characteristic using multidimensional scales, providing precious information
      about its prevalence and clinical impact. However, these scales are not adapted
      to understand the complex dynamics of fatigue in real-life settings and should be
      augmented with ecological assessment of fatigue. The state level of fatigue must
      also be considered during physical tasks as severe fatigue can emerge rapidly
      during exercise. CRD patients exhibit alterations in both peripheral and central
      nervous systems and these abnormalities can be exacerbated during exercise.
      Laboratory tests are necessary to provide mechanistic insights into how and why
      fatigue develops during exercise in CRD. A better knowledge of the
      neurophysiological mechanisms underlying perceived and performance fatigability
      and their influence on real-life performance will enable the development of new
      individualized countermeasures. This review aims first to shed light on the
      terminology of fatigue and then critically considers the contemporary models of
      fatigue and their relevance in the particular context of CRD. This article then
      briefly reports the prevalence and clinical consequences of fatigue in CRD and
      discusses the strengths and weaknesses of various fatigue scales. This review
      also provides several arguments to select the ideal test of performance
      fatigability in CRD and to translate the mechanistic laboratory findings into the
      clinical practice and real-world performance. Finally, this article discusses the
      dose-response relationship to training and the feasibility and validity of using
      the fatigue produced during exercise training sessions in CRD to optimize
      exercise training efficiency. Methodological concerns, examples of applications
      in selected diseases and avenues for future research are also provided.

PMID- 30283350
TI  - Aged Nicotinamide Riboside Kinase 2 Deficient Mice Present an Altered Response to
      Endurance Exercise Training.
AB  - Background: Skeletal muscle aging is marked by the development of a sarcopenic
      phenotype, a global decline of muscle energetic capacities, and an intolerance to
      exercise. Among the metabolic disorders involved in this syndrome, NAD metabolism
      was shown to be altered in skeletalmuscle, with an important role for the NAMPT
      enzyme recycling the nicotinamide precursor. An alternative pathway for NAD
      biosynthesis has been described for the nicotinamide riboside vitamin B3
      precursor used by the NMRK kinases, including the striated muscle-specific NMRK2.
      Aim: With this study, our goal is to explore the ability of 16-month-old Nmrk2 -/
      mice to perform endurance exercise and study the consequences on muscle
      adaptation to exercise. Methods: 10 control and 6 Nmrk2 -/- mice were used and
      randomly assigned to sedentary and treadmill endurance training groups. After 9
      weeks of training, heart and skeletal muscle samples were harvested and used for
      gene expression analysis, NAD levels measurements and immunohistochemistry
      staining. Results: Endurance training triggered a reduction in the expression of
      Cpt1b and AcadL genes involved in fatty acid catabolism in the heart of Nmrk2 -/-
      mice, not in control mice. NAD levels were not altered in heart or skeletal
      muscle, nor at baseline neither after exercise training in any group. Myh7 gene
      encoding for the slow MHC-I was more strongly induced by exercise in Nmrk2 -/-
      mice than in controls. Moreover, IL-15 expression levels is higher in Nmrk2 -/-
      mice skeletal muscle at baseline compared to controls. No fiber type switch was
      observed in plantaris after exercise, but fast fibers diameter was reduced in
      aged control mice, not in Nmrk2 -/- mice. No fiber type switch or diameter
      modification was observed in soleus muscle. Conclusion: In this study, we
      demonstrated for the first time a phenotype in old Nmrk2 -/- mice in response to
      endurance exercise training. Although NMRK2 seems to be predominantly dispensable
      to maintain global NAD levels in heart and skeletal muscle, we demonstrated a
      maladaptive metabolic response to exercise in cardiac and skeletal muscle,
      showing that NMRK2 has a specific and restricted role in NAD signaling compared
      to the NAMPT pathway.

PMID- 30283351
TI  - S100A4 as a Target of the E3-Ligase Asb2beta and Its Effect on Engineered Heart
      Tissue.
AB  - Background: S100A4 has recently emerged as an important player in cardiac
      disease, affecting phenotype development in animal models of myocardial
      infarction and pathological cardiac hypertrophy, albeit it is unclear whether
      S100A4 exerts a detrimental or beneficial function. The goal of the current study
      was to analyze S100A4 expression in models of cardiac pathology, investigate its
      degradation by the ubiquitin-proteasome system (UPS), and furthermore examine the
      functional effects of S100A4 levels in a 3D model of engineered heart tissue
      (EHT). Methods and Results: S100A4 mRNA and protein levels were analyzed in
      different models of cardiac pathology via quantitative RT-PCR and Western blot,
      showing a higher S100A4 steady-state protein concentration in hearts of Mybpc3
      knock-in (KI) hypertrophic cardiomyopathy (HCM) mice. COS-7 cells co-transfected
      with plasmids encoding mutant (MUT) Asb2beta lacking the E3 ligase activity in
      combination with V5-tagged S100A4 plasmid presented higher S100A4-V5 protein
      steady-state concentrations than cells co-transfected with the Asb2beta wild type
      (WT) plasmid. This effect was blunted by treatment with the specific proteasome
      inhibitor epoxomicin. Adeno-associated virus serotype 6 (AAV6)-mediated S100A4
      overexpression in a 3D model of EHT did not affect contractile parameters.
      Immunofluorescence analysis showed a cytosolic and partly nuclear expression
      pattern of S100A4. Gene expression analysis in EHTs overexpressing S100A4-V5
      showed markedly lower steady-state concentrations of genes involved in cardiac
      fibrosis and pathological cardiac hypertrophy. Conclusion: We showed that S100A4
      protein level is higher in cardiac tissue of Mybpc3-KI HCM mice probably as a
      result of a lower degradation by the E3 ligase Asb2beta. While an overexpression
      of S100A4 did not alter contractile parameters in EHTs, downstream gene
      expression analysis points toward modulation of signaling cascades involved in
      fibrosis and hypertrophy.

PMID- 30283352
TI  - Quantification of Biventricular Strains in Heart Failure With Preserved Ejection
      Fraction Patient Using Hyperelastic Warping Method.
AB  - Heart failure (HF) imposes a major global health care burden on society and
      suffering on the individual. About 50% of HF patients have preserved ejection
      fraction (HFpEF). More intricate and comprehensive measurement-focused imaging of
      multiple strain components may aid in the diagnosis and elucidation of this
      disease. Here, we describe the development of a semi-automated hyperelastic
      warping method for rapid comprehensive assessment of biventricular
      circumferential, longitudinal, and radial strains that is physiological
      meaningful and reproducible. We recruited and performed cardiac magnetic
      resonance (CMR) imaging on 30 subjects [10 HFpEF, 10 HF with reduced ejection
      fraction patients (HFrEF) and 10 healthy controls]. In each subject, a three
      dimensional heart model including left ventricle (LV), right ventricle (RV), and
      septum was reconstructed from CMR images. The hyperelastic warping method was
      used to reference the segmented model with the target images and biventricular
      circumferential, longitudinal, and radial strain-time curves were obtained. The
      peak systolic strains are then measured and analyzed in this study. Intra- and
      inter-observer reproducibility of the biventricular peak systolic strains was
      excellent with all ICCs > 0.92. LV peak systolic circumferential, longitudinal,
      and radial strain, respectively, exhibited a progressive decrease in magnitude
      from healthy control->HFpEF->HFrEF: control (-15.5 +/- 1.90, -15.6 +/- 2.06, 41.4
      +/- 12.2%); HFpEF (-9.37 +/- 3.23, -11.3 +/- 1.76, 22.8 +/- 13.1%); HFrEF (-4.75
      +/- 2.74, -7.55 +/- 1.75, 10.8 +/- 4.61%). A similar progressive decrease in
      magnitude was observed for RV peak systolic circumferential, longitudinal and
      radial strain: control (-9.91 +/- 2.25, -14.5 +/- 2.63, 26.8 +/- 7.16%); HFpEF (
      7.38 +/- 3.17, -12.0 +/- 2.45, 21.5 +/- 10.0%); HFrEF (-5.92 +/- 3.13, -8.63 +/-
      2.79, 15.2 +/- 6.33%). Furthermore, septum peak systolic circumferential,
      longitudinal, and radial strain magnitude decreased gradually from healthy
      control to HFrEF: control (-7.11 +/- 1.81, 16.3 +/- 3.23, 18.5 +/- 8.64%); HFpEF
      (-6.11 +/- 3.98, -13.4 +/- 3.02, 12.5 +/- 6.38%); HFrEF (-1.42 +/- 1.36, -8.99 +/
      2.96, 3.35 +/- 2.95%). The ROC analysis indicated LV peak systolic
      circumferential strain to be the most sensitive marker for differentiating HFpEF
      from healthy controls. Our results suggest that the hyperelastic warping method
      with the CMR-derived strains may reveal subtle impairment in HF biventricular
      mechanics, in particular despite a "normal" ventricular ejection fraction in
      HFpEF.

PMID- 30283353
TI  - TP63 Transcripts Play Opposite Roles in Chicken Skeletal Muscle Differentiation.
AB  - Tumor protein 63 (TP63) comprises multiple isoforms and plays an important role
      during embryonic development. It has been shown that TP63 knockdown inhibits
      myogenic differentiation, but which isoform is involved in the underlying
      myogenic regulation remains uncertain. Here, we found that two transcripts of
      TP63, namely, TAp63alpha and DeltaNp63alpha, are expressed in chicken skeletal
      muscle. These two transcripts have distinct expression patterns and opposite
      functions in skeletal muscle development. TAp63 has higher expression in skeletal
      muscle than in other tissues, and its expression is gradually upregulated during
      chicken primary myoblast differentiation. DeltaNp63 can be expressed in multiple
      tissues and exhibits stable expression during myoblast differentiation.
      TAp63alpha overexpression inhibits myoblast proliferation, induces cell cycle
      arrest, and enhances myoblast differentiation. However, although DeltaNp63alpha
      has no significant effect on cell proliferation, the overexpression of
      DeltaNp63alpha inhibits myoblast differentiation. Using isoform-specific
      overexpression assays following RNA-sequencing, we identified potential
      downstream genes of TAp63alpha and DeltaNp63alpha in myoblast. Bioinformatics
      analyses and experimental verification results showed that the differentially
      expressed genes (DEGs) between the TAp63alpha and control groups were enriched in
      the cell cycle pathway, whereas the DEGs between the DeltaNp63alpha and control
      groups were enriched in muscle system process, muscle contraction, and myopathy.
      These findings provide new insights into the function and expression of TP63
      during skeletal muscle development, and indicate that one gene may play two
      opposite roles during a single cellular process.

PMID- 30283354
TI  - Partial Mechanical Unloading of the Heart Disrupts L-Type Calcium Channel and
      Beta-Adrenoceptor Signaling Microdomains.
AB  - Introduction: We investigated the effect of partial mechanical unloading (PMU) of
      the heart on the physiology of calcium and beta-adrenoceptor-cAMP (betaAR-cAMP)
      microdomains. Previous studies have investigated PMU using a model of heterotopic
      heart and lung transplantation (HTHAL). These studies have demonstrated that PMU
      disrupts the structure of cardiomyocytes and calcium handling. We sought to
      understand these processes by studying L-Type Calcium Channel (LTCC) activity and
      sub-type-specific betaAR-cAMP signaling within cardiomyocyte membrane
      microdomains. Method: We utilized an 8-week model of HTHAL, whereby the hearts of
      syngeneic Lewis rats were transplanted into the abdomens of randomly assigned
      cage mates. A pronounced atrophy was observed in hearts after HTHAL.
      Cardiomyocytes were isolated via enzymatic perfusion. We utilized Forster
      Resonance Energy Transfer (FRET) based cAMP-biosensors and scanning ion
      conductance microscopy (SICM) based methodologies to study localization of LTCC
      and betaAR-cAMP signaling. Results: beta2AR-cAMP responses measured by FRET in
      the cardiomyocyte cytosol were reduced by PMU (loaded 28.51 +/- 7.18% vs.
      unloaded 10.84 +/- 3.27% N,n 4/10-13 mean +/- SEM * p < 0.05). There was no
      effect of PMU on beta2AR-cAMP signaling in RII_Protein Kinase A domains. beta1AR
      cAMP was unaffected by PMU in either microdomain. Consistent with this SICM/FRET
      analysis demonstrated that beta2AR-cAMP was specifically reduced in t-tubules
      (TTs) after PMU (loaded TT 0.721 +/- 0.106% vs. loaded crest 0.104 +/- 0.062%,
      unloaded TT 0.112 +/- 0.072% vs. unloaded crest 0.219 +/- 0.084% N,n 5/6-9 mean
      +/- SEM ** p < 0.01, *** p < 0.001 vs. loaded TT). By comparison beta1AR-cAMP
      responses in either TT or sarcolemmal crests were unaffected by the PMU. LTCC
      occurrence and open probability (Po) were reduced by PMU (loaded TT Po 0.073 +/-
      0.011% vs. loaded crest Po 0.027 +/- 0.006% N,n 5/18-26 mean +/- SEM * p < 0.05)
      (unloaded TT 0.0350 +/- 0.003% vs. unloaded crest Po 0.025 N,n 5/20-30 mean +/-
      SEM NS # p < 0.05 unloaded vs. loaded TT). We discovered that PMU had reduced the
      association between Caveolin-3, Junctophilin-2, and Cav1.2. Discussion: PMU
      suppresses' beta2AR-cAMP and LTCC activity. When activated, the signaling of
      beta2AR-cAMP and LTCC become more far-reaching after PMU. We suggest that a
      situation of 'suppression/decompartmentation' is elicited by the loss of refined
      cardiomyocyte structure following PMU. As PMU is a component of modern device
      therapy for heart failure this study has clinical ramifications and raises
      important questions for regenerative medicine.

PMID- 30283355
TI  - Modulation of Cardiac Alternans by Altered Sarcoplasmic Reticulum Calcium
      Release: A Simulation Study.
AB  - Background: Cardiac alternans is an important precursor to arrhythmia,
      facilitating formation of conduction block, and re-entry. Diseased hearts were
      observed to be particularly vulnerable to alternans, mainly in heart failure or
      after myocardial infarction. Alternans is typically linked to oscillation of
      calcium cycling, particularly in the sarcoplasmic reticulum (SR). While the role
      of SR calcium reuptake in alternans is well established, the role of altered
      calcium release by ryanodine receptors has not yet been studied extensively. At
      the same time, there is strong evidence that calcium release is abnormal in heart
      failure and other heart diseases, suggesting that these changes might play a pro
      alternans role. Aims: To demonstrate how changes to intracellular calcium release
      dynamics and magnitude affect alternans vulnerability. Methods: We used the state
      of-the-art Heijman-Rudy and O'Hara-Rudy computer models of ventricular myocyte,
      given their detailed representation of calcium handling and their previous
      utility in alternans research. We modified the models to obtain precise control
      over SR release dynamics and magnitude, allowing for the evaluation of these
      properties in alternans formation and suppression. Results: Shorter time to peak
      SR release and shorter release duration decrease alternans vulnerability by
      improved refilling of releasable calcium within junctional SR; conversely, slow
      release promotes alternans. Modulating the total amount of calcium released, we
      show that sufficiently increased calcium release may surprisingly prevent
      alternans via a mechanism linked to the functional depletion of junctional SR
      during release. We show that this mechanism underlies differences between "eye
      type" and "fork-type" alternans, which were observed in human in vivo and in
      silico. We also provide a detailed explanation of alternans formation in the
      given computer models, termed "sarcoplasmic reticulum calcium cycling
      refractoriness." The mechanism relies on the steep SR load-release relationship,
      combined with relatively limited rate of junctional SR refilling. Conclusion:
      Both altered dynamics and magnitude of SR calcium release modulate alternans
      vulnerability. In particular, slow dynamics of SR release, such as those observed
      in heart failure, promote alternans. Therefore, acceleration of intracellular
      calcium release, e.g., via synchronization of calcium sparks, may inhibit
      alternans in failing hearts and reduce arrhythmia occurrence.

PMID- 30283357
TI  - A Medal in the Olympics Runs in the Family: A Cohort Study of Performance
      Heritability in the Games History.
AB  - Introduction: Elite performance in sports is known to be influenced by heritable
      components, but the magnitude of such an influence has never been quantified.
      Hypothesis/Objectives: We hypothesized that having a former world-class champion
      in the family increases the chances of an athlete to repeat the achievement of
      her or his kinship. We aimed to measure the heritability of a medal in the
      Olympic Games (OG) among Olympians and to estimate the percentage of the genetic
      contribution to such a heritance. Study Design: Twin-family study of a
      retrospective cohort. Methods: All the 125,051 worldwide athletes that have
      participated in the OG between 1896 and 2012 were included. The expected
      probability to win a medal in the OG was defined as the frequency of medallists
      among Olympians without any blood kinship in the OG. This expected probability
      was compared with the probability to win a medal for Olympians having a kinship
      (grandparent, aunt/uncle, parent, or siblings) with a former Olympian that was a
      (1) non-medallist or (2) medallist. The heritability of the genetically
      determined phenotype (h2) was assessed by probandwise concordance rates among
      dizygotic (DZ) and monozygotic (MZ) twins (n = 90). Results: The expected
      probability to win a medal in the OG was 20.4%. No significant difference of
      medal probability was found in the subgroups of Olympians with a Non-medallist
      kinship, except among siblings for whom this probability was lower: 13.3% (95% CI
      11.2-14.8). The medal probability was significantly greater among Olympians
      having a kinship with a former Olympic Medallist: 44.4% for niece/nephew (33.7
      54.2); 43.4% for offspring (37.4-48.6); 64.8% for siblings (61.2-68.8); 75.5% for
      DZ twins (63.3-86.6); and 85.7% for MZ twins (63.6-96.9); with significantly
      greater concordance between MZ than DZ (p = 0.01) and h2 estimated at 20.5%.
      Conclusion: Having a kinship with a former Olympic medallist is associated with a
      greater probability for an Olympian to also become a medallist, the closer an
      athlete is genetically to such kinship the greater this probability. Once in the
      OG, the genetic contribution to win a medal is estimated to be 20.5%.

PMID- 30283358
TI  - FasL Modulates Expression of Mmp2 in Osteoblasts.
AB  - FasL is a well-known actor in the apoptotic pathways but recent reports have
      pointed to its important novel roles beyond cell death, as observed also for bone
      cells. This is supported by non-apoptotic appearance of FasL during osteogenesis
      and by significant bone alterations unrelated to apoptosis in FasL deficient
      (gld) mice. The molecular mechanism behind this novel role has not yet been
      revealed. In this report, intramembranous bone, where osteoblasts differentiate
      directly from mesenchymal precursors without intermediary chondrogenic step, was
      investigated. Mouse mandibular bone surrounding the first lower molar was used as
      a model. The stage where a complex set of bone cells (osteoblasts, osteocytes,
      osteoclasts) is first present during development was selected for an initial
      examination. Immunohistochemical staining detected FasL in non-apoptotic cells at
      this stage. Further, FasL deficient vs. wild type samples subjected to osteogenic
      PCR Array analysis displayed a significantly decreased expression of Mmp2 in gld
      bone. To examine the possibility of this novel FasL-Mmp2 relationship,
      intramembranous bone-derived osteoblastic cells (MC3T3-E1) were treated with anti
      FasL antibody or rmFasL. Indeed, the FasL neutralization caused a decreased
      expression of Mmp2 and rmFasL added to the cells resulted in the opposite effect.
      Since Mmp2 -/- mice display age-dependent alterations in the intramembranous
      bone, early stages of gld mandibular bone were examined and age-dependent
      phenotype was confirmed also in gld mice. Taken together, the present in vivo and
      in vitro findings point to a new non-apoptotic function of FasL in bone
      development associated with Mmp2 expression.

PMID- 30283359
TI  - Lysophosphatidic Acid Is Associated With Cardiac Dysfunction and Hypertrophy by
      Suppressing Autophagy via the LPA3/AKT/mTOR Pathway.
AB  - Background: Lysophosphatidic acid (LPA), as a phospholipid signal molecule,
      participates in the regulation of various biological functions. Our previous
      study demonstrated that LPA induces cardiomyocyte hypertrophy in vitro; however,
      the functional role of LPA in the post-infarct heart remains unknown. Growing
      evidence has demonstrated that autophagy is involved in regulation of cardiac
      hypertrophy. The aim of the current work was to investigate the effects of LPA on
      cardiac function and hypertrophy during myocardial infarction (MI) and determine
      the regulatory role of autophagy in LPA-induced cardiomyocyte hypertrophy.
      Methods: In vivo experiments were conducted in Sprague-Dawley rats subjected to
      MI surgery or a sham operation, and rats with MI were assigned to receive an
      intraperitoneal injection of LPA (1 mg/kg) or vehicle for 5 weeks. The in vitro
      experiments were conducted in H9C2 cardiomyoblasts. Results: LPA treatment
      aggravated cardiac dysfunction, increased cardiac hypertrophy, and reduced
      autophagy after MI in vivo. LPA suppressed autophagy activation, as indicated by
      a decreased LC3II-to-LC3I ratio, increased p62 expression, and reduced
      autophagosome formation in vitro. Rapamycin, an autophagy enhancer, attenuated
      LPA-induced autophagy inhibition and H9C2 cardiomyoblast hypertrophy, while
      autophagy inhibition with Beclin1 siRNA did not further enhance the hypertrophic
      response in LPA-treated cardiomyocytes. Moreover, we demonstrated that LPA
      suppressed autophagy through the AKT/mTOR signaling pathway because mTOR and PI3K
      inhibitors significantly prevented LPA-induced mTOR phosphorylation and autophagy
      inhibition. In addition, we found that knockdown of LPA3 alleviated LPA-mediated
      autophagy suppression in H9C2 cardiomyoblasts, suggesting that LPA suppresses
      autophagy through activation of the LPA3 and AKT/mTOR pathways. Conclusion: These
      findings suggest that LPA plays an important role in mediating cardiac
      dysfunction and hypertrophy after a MI, and that LPA suppresses autophagy through
      activation of the LPA3 and AKT/mTOR pathways to induce cardiomyocyte hypertrophy.

PMID- 30283356
TI  - Guidance Molecules in Vascular Smooth Muscle.
AB  - Several highly conserved families of guidance molecules, including ephrins,
      Semaphorins, Netrins, and Slits, play conserved and distinct roles in tissue
      remodeling during tissue patterning and disease pathogenesis. Primarily, these
      guidance molecules function as either secreted or surface-bound ligands that
      interact with their receptors to activate a variety of downstream effects,
      including cell contractility, migration, adhesion, proliferation, and
      inflammation. Vascular smooth muscle cells, contractile cells comprising the
      medial layer of the vessel wall and deriving from the mural population, regulate
      vascular tone and blood pressure. While capillaries lack a medial layer of
      vascular smooth muscle, mural-derived pericytes contribute similarly to capillary
      tone to regulate blood flow in various tissues. Furthermore, pericyte coverage is
      critical in vascular development, as perturbations disrupt vascular permeability
      and viability. During cardiovascular disease, smooth muscle cells play a more
      dynamic role in which suppression of contractile markers, enhanced proliferation,
      and migration lead to the progression of aberrant vascular remodeling. Since many
      types of guidance molecules are expressed in vascular smooth muscle and
      pericytes, these may contribute to blood vessel formation and aberrant remodeling
      during vascular disease. While vascular development is a large focus of the
      existing literature, studies emerged to address post-developmental roles for
      guidance molecules in pathology and are of interest as novel therapeutic targets.
      In this review, we will discuss the roles of guidance molecules in vascular
      smooth muscle and pericyte function in development and disease.

PMID- 30283360
TI  - Proteomics Analysis of Myocardial Tissues in a Mouse Model of Coronary
      Microembolization.
AB  - Coronary microembolization (CME) is an important clinical problem, and it is
      related to poor outcome. The specific molecular mechanisms of CME are not fully
      understood. In the present study, we established a mice model of CME. Isobaric
      tags for relative and absolute quantitation (iTRAQ) and liquid chromatography
      coupled with tandem mass spectrometry (LC-MS/MS) technologies identified 249
      differentially expressed proteins in the myocardial tissues of CME mice as
      compared with sham-operated mice. Bioinformatics analysis demonstrated that these
      differentially expressed proteins were enriched in several energy metabolism or
      cytoskeleton organization related processes or pathways. Quantitative PCR and
      Western blotting validation experiments revealed that succinate dehydrogenase
      (SDHA and SDHB) were upregulated, Rho GDP dissociation inhibitor alpha
      (RhoGDIalpha) and Filamin-A (FLNA) were downregulated significantly in CME mice.
      These findings indicated that the alternations of the cytoskeleton and energy
      metabolism pathways play important roles in the pathogenesis of CME, future
      studies are warranted to verify if targeting these molecules might be useful to
      alleviate CME injury or not.

PMID- 30283361
TI  - Additional Intra- or Inter-session Balance Tasks Do Not Interfere With the
      Learning of a Novel Balance Task.
AB  - Background: It has been shown that balance training induces task-specific
      performance improvements with very limited transfer to untrained tasks. Thus,
      regarding fall prevention, one strategy is to practice as many tasks as possible
      to be prepared for a multitude of situations with increased fall risk. However,
      it is not clear whether the learning of several different balance tasks interfere
      with each other. A positive influence could be possible via the contextual
      interference (CI) effect, a negative influence could be induced by the disruption
      of motor memory during consolidation or retrieval. Methods: In two 3-week
      training experiments, we tested: (1) whether adding an additional balance task in
      the same training session would influence the learning of a balance task [first
      task: one-leg stance on a tilt-board (TB), six sessions, 15 * 20 s per session;
      additional task: one-leg stance on a slack line (SL), same amount of additional
      training]; (2) whether performing a different balance task (SL) in between
      training sessions of the first task (TB) would influence the learning of the
      first task. Twenty-six healthy subjects participated in the first experiment, 40
      in the second experiment. In both experiments the participants were divided into
      three groups, TB only, TB and SL, and control. Before and after the training
      period, performance during the TB task (3 * 20 s) was recorded with a Vicon
      motion capturing system to assess the time in equilibrium. Results: Analyses of
      variance revealed that neither the additional intra-session balance task in
      experiment 1 nor the inter-session task in experiment 2 had a significant effect
      on balance performance improvement in the first task (no significant group * time
      interaction effect for the training groups, p = 0.83 and p = 0.82, respectively,
      only main effects of time). Conclusion: We could not find that additional intra-
      or intersession balance tasks interfere with the learning of a balance task,
      neither impairing it nor having a significant positive effect. This can also be
      interpreted as further evidence for the specificity of balance training effects,
      as different balance tasks do not seem to elicit interacting adaptations.

PMID- 30283362
TI  - A Review of the Inhibition of the Mitochondrial ATP Synthase by IF1 in vivo:
      Reprogramming Energy Metabolism and Inducing Mitohormesis.
AB  - The ATPase Inhibitory Factor 1 (IF1) is the physiological inhibitor of the
      mitochondrial ATP synthase. Herein, we summarize the regulation of the expression
      and activity of IF1 as a main driver of the activity of oxidative phosphorylation
      (OXPHOS) in mammalian tissues. We emphasize that the expression of IF1, which is
      a mitochondrial protein with very short half-life, is tissue-specifically
      expressed and primarily controlled at posttranscriptional levels. Inhibition of
      the activity of IF1 as inhibitor of the ATP synthase under normal physiological
      conditions is exerted by phosphorylation of S39 by a cAMP-dependent PKA-like
      activity of mitochondria in response to different physiological cues. Conditional
      tissue-specific transgenic mice overexpressing IF1 in colon, or a mutant active
      version of IF1 (IF1-H49K) in liver or in neurons, revealed the inhibition of the
      ATP synthase and the reprograming of energy metabolism to an enhanced glycolysis.
      In the IF1-H49K models, the assembly/activity of complex IV and the superassembly
      of complex V are also affected. Moreover, the IF1-mediated inhibition of the ATP
      synthase generates a reactive oxygen species (mtROS) signal that switches on the
      expression of nuclear genes that facilitate adaptation to a restrained OXPHOS. In
      contrast to normal mice, metabolically preconditioned animals are partially
      protected from the action of cytotoxic agents by upgrading the activation of
      stress kinases and transcription factors involved in resolving metabolic
      adaptation, the antioxidant response, cell survival, and the immune response of
      the tissue microenvironment. Altogether, we stress a fundamental physiological
      function for the ATP synthase and its inhibitor in mitohormesis.

PMID- 30283365
TI  - Mental Health in Anesthesiology and ICU Staff: Sense of Coherence Matters.
AB  - Background: Hospitals, and particularly intensive care units (ICUs), are
      demanding and stressful workplaces. Physicians and nurse staff are exposed to
      various stressors: emergency situations, patients' deaths, and team conflicts.
      Correspondingly, several studies describe increased rates of PTSD symptoms and
      other mental health problems in hospital staff. Therefore, it is important to
      identify factors that lower the risk of psychopathological symptoms. High levels
      of sense of coherence (SOC) and general resilience as well as an internal locus
      of control (LOC) have already been identified as important health-benefitting
      factors in medical staff. The current study aimed to evaluate their unique impact
      in an ICU and an anesthesiology unit. Method: The cross-sectional online survey
      investigated SOC, LOC, general resilience, general mental health problems as well
      as PTSD symptoms in nurses and physicians within an ICU and an anesthesiology
      unit (N = 52, 65.4% female). General mental health problems were assessed using
      the ICD-10-Symptom-Rating (ISR) and PTSD symptoms were measured using the PTSD
      Checklist for DSM-5 (PCL-5). The Sense of Coherence Scale (SOC-L9) assessed SOC,
      the Resilience Scale (RS-11) measured general resilience, and LOC was determined
      using a 4-item scale for the assessment of control beliefs (IE-4). Results: As
      expected, SOC, r = -0.72, p < 0.001, general resilience, r = -0.46, p < 0.001,
      and internal LOC, r = -0.51, p < 0.001, were negatively correlated with general
      mental health problems while an external LOC showed a positive association, r =
      0.35, p = 0.010. However, in a multiple regression model, R 2 = 53.9%, F (4, 47)
      = 13.73, p < 0.001, only SOC significantly predicted general mental health
      problems by uniquely accounting for 13% of the variance. For PTSD symptoms, which
      were highly correlated with general mental health problems, a similar pattern of
      results was found. Conclusion: SOC was found to be the most important correlate
      of both general mental health problems and PTSD symptoms in an ICU and an
      anesthesiology unit. Thus, if further evidenced by longitudinal studies,
      implementing interventions focusing on an enhancement of SOC in training programs
      for ICU and anesthesiology unit staff might be a promising approach to prevent or
      reduce psychopathological symptoms.

PMID- 30283363
TI  - Efficacy and Safety of Varenicline for Smoking Cessation in Schizophrenia: A Meta
      Analysis.
AB  - Objective: Smoking represents a major public health problem among patients with
      schizophrenia. To this end, some studies have investigated the efficacy of
      varenicline for facilitating smoking cessation in schizophrenia patients. The
      present review seeks to synthesize the results of these studies as well as
      document the reported side effects of using this medication. Methods: An
      electronic search was performed using five major databases: PubMed, Scopus,
      EMBASE, Web of Science, and Cochrane Library. Included in the current analysis
      were randomized clinical trials (RCTs) that have investigated the effect of
      varenicline in promoting smoking cessation in patients with schizophrenia. Risk
      of bias among included RCTs was assessed using the Cochrane Collaboration's
      quality assessment tool. Results: Among the 828 screened articles, only four
      RCTs, which involved 239 participants, were eligible for meta-analysis. In
      patients with schizophrenia, varenicline treatment when compared to placebo
      significantly reduced the number of cigarettes consumed per day [SMD (95% CI) =
      0.89(0.57-1.22)] and expired carbon monoxide levels [SMD (95% CI) = 0.50 (0.06
      0.94)] respectively. Conclusion: Despite a limited number of studies included in
      the meta-analysis, our results suggest that varenicline is an effective and safe
      drug to assist smoking cessation in patients with schizophrenia. Future large
      scale well-designed RCTs are required to validate these findings.

PMID- 30283366
TI  - Larger Numbers of Glial and Neuronal Cells in the Periaqueductal Gray Matter of
      MU-Opioid Receptor Knockout Mice.
AB  - Background: MU-opioid receptor knockout (MOP-KO) mice display baseline
      hyperalgesia. We have recently identified changes in tissue volume in the
      periaqueductal gray matter (PAG) using magnetic resonance imaging voxel-based
      morphometry. Changes in the structure and connectivity of this region might
      account for some behavior phenotypes in MOP-KO mice, including hyperalgesia.
      Methods: Adult male MOP-KO and wild-type (WT) mice were studied.
      Immunohistochemistry was performed to detect microglia, astrocytes, and neurons
      in the PAG using specific markers: ionized calcium-binding adaptor molecule 1
      (Iba-1) for microglia, glial fibrillary acidic protein (GFAP) for astrocytes, and
      the neuronal nuclei antigen (NeuN; product of the Rbfox3 gene) for neurons,
      respectively. Cell counting was performed in the four parallel longitudinal
      columns of the PAG (dorsomedial, dorsolateral, lateral, and ventrolateral) at
      three different locations from bregma (-3.5, -4.0, and -4.5 mm). Results: The
      quantitative analysis showed larger numbers of well-distributed Iba1-IR cells
      (microglia), NeuN-IR cells (neurons), and GFAP-IR areas (astrocytes) at all the
      anatomically distinct regions examined, namely, the dorsomedial (DM) PAG,
      dorsolateral (DL) PAG, lateral (L) PAG, and ventrolateral (VL) PAG, in MOP-KO
      mice than in control mice. Conclusions: The cellular changes in the PAG
      identified in this paper may underlie aspects of the behavioral alterations
      produced by MOP receptor deletion, and suggest that alterations in the cellular
      structure of the PAG may contribute to hyperalgesic states.

PMID- 30283364
TI  - Synthesis, Biological Evaluation, and SAR Studies of 14beta-phenylacetyl
      Substituted 17-cyclopropylmethyl-7, 8-dihydronoroxymorphinones Derivatives:
      Ligands With Mixed NOP and Opioid Receptor Profile.
AB  - A series of 14beta-acyl substituted 17-cyclopropylmethyl-7,8
      dihydronoroxymorphinone compounds has been synthesized and evaluated for affinity
      and efficacy for mu (MOP), kappa (KOP), and delta (DOP) opioid receptors and
      nociceptin/orphanin FQ peptide (NOP) receptors. The majority of the new ligands
      displayed high binding affinities for the three opioid receptors, and moderate
      affinity for NOP receptors. The affinities for NOP receptors are of particular
      interest as most classical opioid ligands do not bind to NOP receptors. The
      predominant activity in the [35S]GTPgammaS assay was partial agonism at each
      receptor. The results are consistent with our prediction that an appropriate
      14beta side chain would access a binding site within the NOP receptor and result
      in substantially higher affinity than displayed by the parent compound
      naltrexone. Molecular modeling studies, utilizing the recently reported structure
      of the NOP receptor, are also consistent with this interpretation.

PMID- 30283368
TI  - Psychopathology-a Precision Tool in Need of Re-sharpening.
AB  - Psychopathology is the scientific exploration of abnormal mental states that, for
      more than a century, has provided a Gestalt for psychiatric disorders and guided
      clinical as well as scientific progress in modern psychiatry. In the wake of the
      immense technical advances, however, psychopathology has been increasingly
      marginalized by neurobiological, genetic, and neuropsychological research. This
      ongoing erosion of psychiatric phenomenology is further fostered by clinical
      casualness as well as pressured health care and research systems. The skill to
      precisely and carefully assess psychopathology in a qualified manner used to be a
      core attribute of mental health professionals, but today's curricula pay
      increasingly less attention to its training, thus blurring the border between
      pathology and variants of the "normal" further. Despite all prophecies that
      psychopathology was doomed, and with neurobiological parameters having yet to
      show their differential-diagnostic superiority and value for differential
      indication, psychiatric diagnosis continues to rely exclusively on
      psychopathology in DSM-5 and ICD-11. Their categorical systematic, however, is
      equally challenged, and, supported by advances in machine learning, a
      personalized symptom-based approach to precision psychiatry is increasingly
      advocated. The current paper reviews the objectives of psychopathology and the
      recent debate on the role of psychopathology in future precision psychiatry-from
      guiding neurobiological research by relating neurobiological changes to patients'
      experiences to giving a framework to the psychiatric encounter. It concludes that
      contemporary research and clinic in psychiatry do not need less but rather more
      differentiated psychopathologic approaches in order to develop approaches that
      integrate professional knowledge and patients' experience.

PMID- 30283367
TI  - The Role of Amygdala in Patients With Euthymic Bipolar Disorder During Resting
      State.
AB  - The current study aims to explore the functional changes of the amygdala in
      patients with euthymic Bipolar Disorder (BD) using resting state fMRI (rs-fMRI).
      Twenty-one euthymic patients with bipolar disorder and 28 healthy controls
      participated in this study. Two of the euthymic patients with BD and three of the
      healthy controls were excluded due to excessive head motion. We found that
      patients with euthymia (38.79 +/- 12.03) show higher fALFF (fractional Amplitude
      of low-frequency fluctuation) value of the amygdala (t = 2.076, P = 0.044), and
      lower functional connectivity between the amygdala and supplementary motor area
      (p < 0.01, GRF corrected) than healthy controls (33.40 +/- 8.21). However,
      euthymic patients did not show a differential activity in ReHo (Regional
      Homogeneity) and gray matter of the amygdala region as compared to healthy
      controls. Thus, despite the absence of clinical symptoms in euthymic patients
      with BD, the amygdala functional activity and its connectivity to other brain
      regions remain altered. Further investigation of negative emotions and social
      functioning in euthymic patients with BD are needed and can help pave the way for
      a better understanding of BD psychopathology.

PMID- 30283369
TI  - Recursive Combination Has Adaptability in Diversifiability of Production and
      Material Culture.
AB  - It has been suggested that hierarchically structured symbols, a remarkable
      feature of human language, are produced via the operation of recursive
      combination. Recursive combination is frequently observed in human behavior, not
      only in language but also in action sequences, mind-reading, technology, etc. in
      contrast, it is rarely observed in animals. Why is it that only humans use this
      operation? What is the adaptability of recursive combination? We aim (1) to
      identify the environmental feature(s) in which recursive combination is effective
      for survival and reproduction, and that has facilitated the evolution of this
      ability, and (2) to demonstrate the possible evolutionary processes of recursive
      combination. To achieve this, we constructed an evolutionary simulation of agents
      that generated products using recursive combination and used the results to
      explore the types of fitness functions (that reflect the kinds of adaptive
      environments) that give rise to this ability. We identified two types of
      adaptability of the recursive combination: (1) diversifiability of production and
      (2) diversifiability of products. Through the former, recursive combination
      promotes robustness against failure of production caused by inaccurate
      manipulations or irreversible changes. In an environment in which diversified
      products are preferable, sharing a portion of the production process for these
      products entails producing multiple products in which recursive combination plays
      a key role. We suppose that recursive combination works as a driving force of
      material culture. Finally, we discuss the possible evolutionary scenarios of
      recursive combination that is later generalized to encompass many aspects of
      human cognition, including human language.

PMID- 30283370
TI  - Factor Structure of Urdu Version of the Flourishing Scale.
AB  - Background: A great deal of research has been carried out on the assessment of
      the eudaimonic perspective of psychological well-being and the hedonic
      perspective of subjective well-being. The Flourishing Scale (FS) has been
      extensively used in research and practice, as it assesses the fundamental aspects
      of social psychological functioning. Nevertheless, the psychometric properties of
      Urdu versions of eudaimonic measures, such as the FS, have not yet been
      ascertained. The translation and validation of the FS in the Urdu language was
      not available, and hence this study was planned with the aim to validate the Urdu
      version of the FS. Methods: We assessed the psychometric properties of the FS in
      a sample of adults aged 18 years and above in Pakistan (N = 130) using
      exploratory factor analysis based on principal component analysis with varimax
      rotation and confirmatory factor analysis. Results: The exploratory factor
      analysis confirmed the unidimensional nature of the 8-item FS. We assessed that
      the Urdu version of the FS showed a high internal consistency reliability (alpha
      = 0.914) with a significant intraclass correlation coefficient (ICC), p < 0.001).
      In our study, the Kaiser-Mayer-Olkin value was 0.915 with a chi-square test value
      (chi2) of 637.687, and Bartlett's test of sphericity was significant (df = 28, p
      < 0.001). The intraclass correlation coefficients (ICCs) at test-retest for all
      domains were statistically significant (p < 0.001) and showed excellent agreement
      for all the items. The revised confirmatory factor analysis revealed a good-fit
      model, but with item 8-"People respect me"-removed due to its lower factor
      loading. Conclusions: The findings suggest that the FS is a psychometrically
      sound instrument for assessing social psychological functioning among adults in
      Pakistan. Therefore, the validated Urdu version of the FS may be used in future
      studies of well-being in clinical psychology and positive psychology.

PMID- 30283371
TI  - Steps Toward an Integrative Clinical Systems Psychology.
AB  - Clinical fields of the "sciences of the mind" (psychotherapy, psychiatry, etc.)
      lack integrative conceptual frameworks that have explanatory power. Mainly
      descriptive-classificatory taxonomies like DSM dominate the field. New taxonomies
      such as Research Domain Criteria (RDoC) aim to collect scientific knowledge
      regarding "systems" for "processes" of the brain. These terms have a
      supradisciplinary" meaning if they are considered in context of Systems Science.
      This field emerges as a platform of theories like general systems theory,
      catastrophe theory, synergetics, chaos theory, etc. It provides a lot of abstract
      concepts, constructs, methods and models. We assume that these tools also enable
      theoretical integration in the diversified field of clinical practice in the
      sciences of the mind. Additionally, systems thinking in clinical psychology
      improves conceptual links to currently network-oriented neurobiology. However,
      clear definitions of systemic terms are necessary to emerge from their mainly
      metaphorical use. Here we revise mainly terms like "structure", "process" and
      "dynamics" as they are used already in psychology, psychoanalysis,
      psychopathology and psychiatry in an ill-defined way. For instance, affective
      cognitive structures like "life space" or "object representations" can be seen as
      products of mental processing. These structures, in turn, modulate dynamics of
      mental processes. Additionally, we suggest a coupled network concept of emotions
      and motivations as the main subsystem that modulates mental dynamics that results
      in a qualitative systemic model of the mind. Finally, we assume that a revisited
      systemic approach could improve interdisciplinary understanding of the mental.

PMID- 30283372
TI  - Why Do You Ride?: A Characterization of Mountain Bikers, Their Engagement
      Methods, and Perceived Links to Mental Health and Well-Being.
AB  - Mountain biking is an increasingly popular outdoor activity on the extreme sport
      continuum. Extreme and high-risk sports have been investigated using a variety of
      motivational theories with sensation seeking a dominant theme; however,
      behavioral and motivational homogeneity within these types of populations should
      not be assumed. Recent studies have highlighted the therapeutic potential of
      extreme sports and similar outdoor activities. The aim of this study was to
      describe the characteristics of mountain biking participants, their engagement
      methods, and perceived benefits to mental health and well-being. This was a cross
      sectional survey and participants were recruited via social media. An online
      questionnaire specific to the domain of mountain biking was developed. Analysis
      of the full sample (n = 1,484) and of three independent paired sub-samples was
      conducted using SPSS. The sub-samples compared the results of males and females;
      younger and older riders; and those who have recently engaged in downhill
      mountain biking and those who have not. The results have succeeded in identifying
      some disparities in mountain biker characteristics and engagement methods. The
      results suggest that some riders found pleasure in higher risk engagement. The
      study proposes various explanations for the disproportion of women in mountain
      biking. Irrespective of the confounding factors related to rider characteristics
      or engagement methods, mountain bikers reported copious benefits to mental health
      and well-being related to their engagement. There was a high reported usage of
      mountain biking as a coping strategy. As such, this study provides insights that
      could inform the development of outdoor activities as interventions for mental
      health.

PMID- 30283373
TI  - Exploring Narrative Structure and Hero Enactment in Brand Stories.
AB  - This study examines how audiovisual brand stories both invite and enable
      consumers to enact heroic archetypes. Integrating research on the archetypal
      structure of narratives with research on the event structure of narratives, we
      distinguish singular plot stories (i.e., stories that show a Hero's Journey) from
      embedded plot stories (i.e., stories that not only show but also tell one or more
      Hero's Journeys) and develop a conceptual and narratological framework to analyze
      their structural elements. Application of the framework to 20 brand stories
      representing 8 different brands reveals meaningful variation in elements between
      the singular plot stories and embedded plot stories. Differences in the
      expression of archetypes and event structure are argued to evoke different types
      of Hero enactment which in turn result in different outcomes. We specifically
      hypothesize that the enactment of heroic archetypes in singular plot stories
      primarily results in catharsis (pleasure), whereas the enactment of heroic
      archetypes in embedded plot stories primarily results in an outcome we describe
      as phronesis: a form of moral sense making of the self that advances one's
      practical wisdom and prudence. The final section of the paper discusses how
      cathartic and phronetic outcomes of hero enactment may foster the psychological
      bonding between brand and consumer, and invite consumers to align their moral
      values with the values that are reflected by heroic character traits. The central
      aims of the analysis presented are to provide an exploration of narrative
      phenomena in a reasonably broad range of brand story videos and foremost to
      provide a conceptual framework with an applicable instrument suited to analyze
      relevant categories in these brand stories. The present study is
      interdisciplinary in its approach to a contemporary, developing marketing
      phenomenon, applying psychological modeling of archetypes and heroic values with
      narratological insights on perspective-taking and story structure. Its
      contribution is to systemize, from a narratological viewpoint, how various
      narrative archetypes in brand video stories may contribute to the development of
      brand-consumer relations.

PMID- 30283374
TI  - Social Interaction Patterns of the Disabled People in Asymmetric Social Dilemmas.
AB  - The social participation of the disabled people is unsatisfactory and low, one of
      the reasons often overlooked but of great importance may lie in the disparate
      patterns of social interaction between the disabled people and the abled people.
      The current study respectively recruited 41 and 80 disabled people in two
      experiments and adopted give-some games and public good dilemma to explore social
      interaction patterns between the disabled abled people. The results were as
      follows: (1) the disabled people preferred to interact with the disabled people
      and the abled people preferred to interact with the abled people. (2) The
      disabled abled people had higher cooperation, satisfaction and sense of justice
      when interacting with the disabled people than interacting with the abled people.
      (3) Advantage in the number of the disabled people could reverse their
      disadvantage in the identity. These results are of important practical value,
      which provides related theoretical support for the disabled people's federation
      and communities when carrying out activities for the disabled people.

PMID- 30283375
TI  - Factor Score Regression With Social Relations Model Components: A Case Study
      Exploring Antecedents and Consequences of Perceived Support in Families.
AB  - The family social relations model (SRM) is applied to identify the sources of
      variance in interpersonal dispositions in families, but the antecedents or
      consequences of those sources are rarely investigated. Simultaneous modeling of
      the SRM with antecedents or consequences using structural equation modeling (SEM)
      allows to do so, but may become computationally prohibitive in small samples. We
      therefore consider two factor score regression (FSR) methods: regression and
      Bartlett FSR. Based on full information maximum likelihood (FIML), we derive
      closed-form expressions for the regression and Bartlett factor scores in the
      presence of missingness. A simulation study in both a complete- and incomplete
      case setting compares the performance of these FSR methods with SEM and an ANOVA
      based approach. In both settings, the regression FIML factor scores as
      explanatory variable produces unbiased estimators with precision comparable to
      the SEM-estimators. When SRM-effects are used as dependent variables, none of the
      FSR methods are a suitable alternative for SEM. The latter result deviates from
      previous studies on FSR in more simple settings. As an example, we explore
      whether gender and past victimhood of relational and physical aggression are
      antecedents for family dynamics of perceived support, and whether those dynamics
      predict physical and relational aggression.

PMID- 30283376
TI  - Body-as-Subject in the Four-Hand Illusion.
AB  - In a recent study (Chen et al., 2018), we conducted a series of experiments that
      induced the "four-hand illusion": using a head-mounted display (HMD), the
      participant adopted the experimenter's first-person perspective (1PP) as if it
      was his/her own 1PP. The participant saw four hands via the HMD: the
      experimenter's two hands from the adopted 1PP and the subject's own two hands
      from the adopted third-person perspective (3PP). In the active four-hand
      condition, the participant tapped his/her index fingers, imitated by the
      experimenter. Once all four hands acted synchronously and received synchronous
      tactile stimulations at the same time, many participants felt as if they owned
      two more hands. In this paper, we argue that there is a philosophical implication
      of this novel illusion. According to Merleau-Ponty (1945/1962) and Legrand
      (2010), one can experience one's own body or body-part either as-object or as
      subject but cannot experience it as both simultaneously, i.e., these two
      experiences are mutually exclusive. Call this view the Experiential Exclusion
      Thesis. We contend that a key component of the four-hand illusion-the subjective
      experience of the 1PP-hands that involved both "kinesthetic sense of movement"
      and "visual sense of movement" (the movement that the participant sees via the
      HMD)-provides an important counter-example against this thesis. We argue that it
      is possible for a healthy subject to experience the same body-part both as
      subject and as-object simultaneously. Our goal is not to annihilate the
      distinction between body-as-object and body-as-subject, but to show that it is
      not as rigid as suggested by the phenomenologists.

PMID- 30283378
TI  - Long-Range Correlation Underlying Childhood Language and Generative Models.
AB  - Long-range correlation, a property of time series exhibiting relevant statistical
      dependence between two distant subsequences, is mainly studied in the statistical
      physics domain and has been reported to exist in natural language. By using a
      state-of-the-art method for such analysis, long-range correlation is first shown
      to occur in long CHILDES data sets. To understand why, generative stochastic
      models of language, originally proposed in the cognitive scientific domain, are
      investigated. Among representative models, the Simon model is found to exhibit
      surprisingly good long-range correlation, but not the Pitman-Yor model. Because
      the Simon model is known not to correctly reflect the vocabulary growth of
      natural languages, a simple new model is devised as a conjunct of the Simon and
      Pitman-Yor models, such that long-range correlation holds with a correct
      vocabulary growth rate. The investigation overall suggests that uniform sampling
      is one cause of long-range correlation and could thus have some relation with
      actual linguistic processes.

PMID- 30283377
TI  - Games Used With Serious Purposes: A Systematic Review of Interventions in
      Patients With Cerebral Palsy.
AB  - The purpose of the present systematic review was to examine extant research
      regarding the role of games used seriously in interventions with individuals with
      cerebral palsy. Therefore, PubMed, PsyINFO, Web of Science, Scopus, and IEEE
      databases were used. Search terms included: "serious games" OR "online games" OR
      "video games" OR "videogame" OR "game based" OR "game" AND "intervention" AND
      "cerebral palsy." After the full reading and quality assessment of the papers, 16
      studies met the inclusion criteria. The majority of the studies reported high
      levels of compliance, motivation, and engagement with game-based interventions
      both at home and at the clinical setting intervention. Regarding the
      effectiveness of the use of games, the results of the studies show both positive
      and negative results regarding their effectiveness. The efficacy was reported to
      motor function (i.e., improvements in the arm function, hand coordination,
      functional mobility, balance and gait function, postural control, upper-limbs
      function) and physical activity. Findings of this review suggest that games are
      used as a complement to conventional therapies and not as a substitute.
      Practitioners often struggle to get their patients to complete the assigned
      homework tasks, as patients display low motivation to engage in prescribed
      exercises. Data of this review indicates the use of games as tools suited to
      promote patients' engagement in the therapy and potentiate therapeutic gains.

PMID- 30283379
TI  - Humble Leadership, Psychological Safety, Knowledge Sharing, and Follower
      Creativity: A Cross-Level Investigation.
AB  - The leadership literature has provided growing evidence regarding the power of
      leadership in facilitating follower creativity. Despite these advances, a
      noticeable omission in this body of research is humble leadership. The study
      extends previous research by developing a cross-level moderated mediation model
      and examining the roles that psychological safety and knowledge sharing may play
      in the relationship between humble leadership and follower creativity. Using a
      time-lagged data of 328 team members nested within 106 teams, the results show
      that: (a) psychological safety mediates the relationship between humble
      leadership and follower creativity; (b) knowledge sharing moderates the
      relationship between psychological safety and follower creativity; and (c) the
      indirect influence of humble leadership on follower creativity through
      psychological safety is stronger when knowledge sharing is high.

PMID- 30283381
TI  - Career Ambition as a Way of Understanding the Relation Between Locus of Control
      and Self-Perceived Employability Among Psychology Students.
AB  - Employability is one of the core concepts for the future career. Students' self
      perceived employability is the concept that connects students' present context of
      education with their future professional engagement. Students' self-perceived
      employability is defined as the capacity to gain and keep employment in line with
      their future qualification level. Locus of control is a concept that explains
      where the person situates the causation of various life events. It is found that
      internal locus of control was related to different aspects of career success.
      Career ambition is regarded as a proxy for students' future career success. Both
      internal locus of control and ambition lead to proactive behaviors that are
      relevant for employability and consequently result in securing a sustainable job.
      The aim of this mixed-method study was to investigate the relations among locus
      of control, ambition and students' self-perceived employability. Firstly, we
      tested mediating role of career ambition in relation of internal locus of control
      and students' self-perceived employability, then we turned to qualitative
      analysis of students' career self-SWOT analyses in order to deepen and enrich
      quantitative findings. The sample consisted of 124 undergraduate psychology
      students that filled out Levenson's Internality subscale from IPC locus of
      control scale, Rothwell et al. (2008) Ambition subscale, and three items
      extracted from the Self-perceived employability subscale. Majority of the survey
      participants (N = 100) filled out personal career SWOT analysis. The mediation
      analysis showed that career ambition had a mediating role in the relation between
      the locus of control and employability. Students perceived personal capabilities
      and ambition as internal strengths and lack of ambition as a major internal
      weakness. As external opportunities students perceived various chances for
      developing professional skills, whereas as external threats they perceived
      limited opportunities in job market. In order to support university students to
      develop employability and future career success, university curricula should
      support developing future work skills that, in addition to functional competences
      and personal resources, entail career ambition, ways of utilizing external
      opportunities and dealing with job market threats.

PMID- 30283380
TI  - The Impact of Postpartum Posttraumatic Stress and Depression Symptoms on Couples'
      Relationship Satisfaction: A Population-Based Prospective Study.
AB  - The couple relationship is of particular importance in the transition to
      parenthood and in the early childhood years because it is related to the well
      being and mental health of partners, children, and the family. One factor that
      may substantially influence relationship quality and couple satisfaction after
      childbirth is the woman's experience of birth. Approximately 2-4% of women
      develop posttraumatic stress disorder (PTSD) after childbirth, with potentially
      wide-ranging negative consequences for the women themselves and their families.
      To date, some qualitative studies have explored the influence of postpartum PTSD
      on couple relationship satisfaction. However, quantitative studies are sparse,
      with mixed results and methodological limitations. We hypothesized that
      postpartum PTSD will be prospectively associated with low couple relationship
      satisfaction, even when taking into account a variety of potential confounding
      variables, and that the effect of postpartum PTSD symptoms on couple relationship
      satisfaction will be mediated by postpartum depression symptoms. This study is
      based on data from the Akershus Birth Cohort study, a prospective cohort study.
      Information from hospital records and questionnaires completed at 17 weeks
      gestational age, as well as at 8 weeks and 2 years postpartum were used (n =
      1480). PTSD symptoms were measured by the Impact of Event Scale and couple
      relationship satisfaction was assessed using a modified version of the Mehrabians
      Marital Satisfaction Scale. Depressive symptoms were assessed by the Edinburgh
      Postnatal Depression Scale. Data were analyzed using bivariate correlations,
      multivariate regression analyses, and mediation analyses. Postpartum PTSD
      symptoms were prospectively related to low couple relationship satisfaction at 2
      years postpartum, even when controlling for a considerable number of background
      factors. When including postpartum depression symptoms as predictor in the
      analyses, the effect of postpartum PTSD was no longer significant. Moreover, more
      detailed analyses showed that postpartum depression symptoms acted as a
      significant mediator, fully explaining the association of postpartum PTSD with
      couples' relationship satisfaction. Early detection of couples' relationship
      problems and the provision of professional help, particularly in high-risk
      couples may not only improve the quality of the couple relationship but also
      improve parenting and promote positive child outcomes.

PMID- 30283382
TI  - Remote Home-Based Virtual Training of Functional Living Skills for Adolescents
      and Young Adults With Intellectual Disability: Feasibility and Preliminary
      Results.
AB  - Background: Virtual Reality (VR) is acquiring increasing credibility as a tool
      for teaching independent living skills to people with Intellectual Disability
      (ID). Generalization of skills acquired during VR training into real environment
      seems to be feasible. Objective: To assess feasibility and verify effectiveness
      of a remote home-based rehabilitation, focused on functional living skills, for
      adolescents and young adults with ID, by using virtual apps installed on tablets.
      In particular, to assess if this tool can be managed independently, if it is
      enjoyable and simple to be used, and if the acquired skills can be generalized to
      the real environment of everyday life. Subjects and method: A single group, pre-
      and post-test research design was used. Sixteen participants with ID were
      included. A digital system was arranged, with a server managing communication
      between the database and the apps installed on tablets. In vivo tests were
      performed before and after the eleven sessions of VR training. Satisfaction
      questionnaires were also administered. Results: Statistically significant
      improvements were found between the pre- and post-in vivo tests, as well as
      between the VR training sessions, in almost all the parameters taken into
      account, for each app. Final questionnaires showed a good satisfaction level for
      both the participants and their families. Conclusion: The highly technological
      system was managed independently by participants with ID, who found it simple to
      be used, useful and even fun; generalization across settings was obtained.
      Results obtained require to be confirmed by future controlled studies, with
      larger samples.

PMID- 30283383
TI  - Information-Based Social Coordination Between Players of Different Skill in
      Doubles Pong.
AB  - We studied how teams of two players of different skill level intercepted
      approaching balls in the doubles-pong task. In this task, the two players moved
      their on-screen paddles along a shared interception axis, so that the approaching
      ball was intercepted by one of the paddles and that the paddles did not collide.
      Earlier work revealed the presence of a fuzzy division of interception space,
      with a boundary between interception domains located in the space between the two
      initial paddle positions. In the present study, using the performance of the
      players in their individual training sessions, we formed teams of players of
      varying skill level. We considered two accounts of how this boundary should be
      understood. In a first account, the players have shared knowledge of this
      boundary. Based on the side of the boundary at which the approaching ball will
      cross the interception axis, the players would decide whose paddle is to make the
      interception. Under this account, we expected that a better-skilled player would
      take responsibility for a larger interception domain, leading to a boundary
      closer to the lesser-skilled player. However, our analyses did not reveal any
      systematic effect of skill difference on the location (or degree of fuzziness) of
      the boundary: location of boundaries and overlap of interception domains varied
      over teams but were not systematically related to skill differences between team
      members. We did find effects of ball speed and approach angle. In a second
      account, the boundary emerges from (information-driven) player-player-ball
      interactions. An action-based model consistent with this account was able to
      capture all the patterns in boundary positions and overlaps that we observed. We
      conclude that the interception patterns that players demonstrate in the doubles
      pong task are best understood as emerging from the unfolding of the dynamics of
      the system of the two players and the ball, coupled through information.

PMID- 30283384
TI  - Do Narcissists Enjoy Visiting Social Networking Sites? It Depends on How Adaptive
      They Are.
AB  - Previous evidence suggests that narcissistic people tend to visit social
      networking sites (SNS) frequently, but the emotions accompanying their engagement
      on such sites has not been a significant subject of study. Therefore, we examined
      the relationship between narcissism and the affective experience on SNS in two
      different samples. To do so, we not only examined narcissism as a whole but also
      distinguished between adaptive and maladaptive narcissism. Results of the two
      studies consistently showed that: (1) narcissism as a whole was not correlated
      with the SNS affective experience; (2) maladaptive narcissism was predictive of a
      worse affective experience on SNS; and (3) partly due to a positive correlation
      with self-esteem, adaptive narcissism was associated with a better SNS affective
      experience. In addition, these findings held with SNS activities considered in
      simultaneity. The present research extends our understanding of the relationship
      between narcissism and social networking as well as that between emotion and
      social networking.

PMID- 30283385
TI  - Moderating Effects of Physical Activity and Global Self-Worth on Internalizing
      Problems in School-Aged Children With Developmental Coordination Disorder.
AB  - School-aged children with developmental coordination disorder (DCD) are at
      greater risk for physical inactivity, lower global self-worth, and internalizing
      problems, such as depression and anxiety. Based on the environmental stress
      hypothesis (ESH), recent research has shown that physical inactivity and lower
      global self-worth sequentially mediate the relationship between DCD and
      internalizing problems, suggesting that DCD leads to lower levels of physical
      activity, which in turn leads to lower levels of global self-worth, and
      ultimately, a greater amount of internalizing problems. However, physical
      activity and global self-worth may also buffer (i.e., moderate) the adverse
      effect of DCD on internalizing problems. To date, this has yet to be tested.
      Participants were 1206 children aged 12-14 years [611 boys, 79 with probable DCD
      (pDCD)]. All children received assessments of motor coordination, physical
      activity, global self-worth, and internalizing problems. Children with pDCD were
      less physically active, had lower self-worth, and experienced more internalizing
      problems compared to typically developing (TD) children (p's < 0.05).
      Furthermore, the moderated moderating effect (three-way interaction) of physical
      activity and global self-worth was also evident (p < 0.05), indicating that
      internalizing problems in both TD and pDCD groups decreased with concurrent
      increases in physical activity and global self-worth. Importantly, when compared
      to TD children, increases in physical activity and global self-worth were
      associated with a greater reduction in internalizing problems among children with
      pDCD. The findings support several pathways in the ESH and highlight that, in
      addition to improving motor skills, interventions should also target both
      physical activity and global self-worth to mitigate potential mental health
      issues for children with motor difficulties.

PMID- 30283386
TI  - Factorial Validity and Invariance of the 7-Item Generalized Anxiety Disorder
      Scale (GAD-7) Among Populations With and Without Self-Reported Psychiatric
      Diagnostic Status.
AB  - The 7-item Generalized Anxiety Disorder Scale (GAD-7) is commonly used to monitor
      anxiety symptoms. However, its factor structure has been inconsistent among
      competing models: unidimensional, two-dimensional, or higher order models.
      Additionally, it is unknown whether the scale has measurement invariance between
      populations with and without self-reported psychiatric diagnostic status.
      Participants were Japanese adults with self-reported anxiety disorder (AD; n =
      479), self-reported AD and major depressive disorder (MDD; n = 314), or without
      self-reported psychiatric diagnostic status (self-reported non-MDD/AD; n = 654),
      who completed this questionnaire on the Internet. Confirmatory factor analyses
      showed the higher order model had similar fit indices to the unidimensional and
      two-dimensional factor models. For the higher order model of GAD-7, metric
      invariance was supported between the self-reported non-MDD/AD and self-reported
      AD status groups, and scalar invariance was supported between the self-reported
      AD status and self-reported AD with MDD status groups. Moreover, convergent and
      discriminant validity were consistent with previous findings in Western cultures.
      These results suggest that factor loadings are equivalent and the construct has
      the same meaning between the self-reported non-MDD/AD and self-reported AD status
      groups, and the total or sub-scale scores were comparable between self-reported
      AD status and self-reported AD with MDD status groups. The major limitation of
      this study is that the participants' diagnoses were self-reported, not confirmed
      by clinical structured interview. Further studies that incorporate clinical
      structured interviews are needed.

PMID- 30283387
TI  - Visualizing Psychological Networks: A Tutorial in R.
AB  - Networks have emerged as a popular method for studying mental disorders.
      Psychopathology networks consist of aspects (e.g., symptoms) of mental disorders
      (nodes) and the connections between those aspects (edges). Unfortunately, the
      visual presentation of networks can occasionally be misleading. For instance,
      researchers may be tempted to conclude that nodes that appear close together are
      highly related, and that nodes that are far apart are less related. Yet this is
      not always the case. In networks plotted with force-directed algorithms, the most
      popular approach, the spatial arrangement of nodes is not easily interpretable.
      However, other plotting approaches can render node positioning interpretable. We
      provide a brief tutorial on several methods including multidimensional scaling,
      principal components plotting, and eigenmodel networks. We compare the strengths
      and weaknesses of each method, noting how to properly interpret each type of
      plotting approach.

PMID- 30283388
TI  - Interactive Learning Environments for the Educational Improvement of Students
      With Disabilities in Special Schools.
AB  - Providing an inclusive and quality education for all contributes toward the
      Sustainable Development Goals of the United Nations. High-quality learning
      environments based on what works in education benefit all students and can be
      particularly beneficial for children with disabilities. This article contributes
      to advance knowledge to enhance the quality of education of students with
      disabilities that are educated in special schools. This research analyses in
      which ways, if any, interactive learning environments can be developed in special
      schools and create better learning opportunities for children with disabilities.
      A case study was conducted with students with disabilities (N = 36) and teaching
      staff in a special school, involving interviews and focus groups. We argue that
      rethinking the learning context by introducing instruction models based on
      interaction benefit children with disabilities and provide high-quality learning
      and safe and supportive relationships for these students, thereby promoting their
      educational and social inclusion.

PMID- 30283389
TI  - The Semantic Content of Abstract Concepts: A Property Listing Study of 296
      Abstract Words.
AB  - The relation of abstract concepts to the modality-specific systems is discussed
      controversially. According to classical approaches, the semantic content of
      abstract concepts can only be coded by amodal or verbal-symbolic representations
      distinct from the sensory and motor systems, because abstract concepts lack a
      clear physical referent. Grounded cognition theories, in contrast, propose that
      abstract concepts do not depend only on the verbal system, but also on a variety
      of modal systems involving perception, action, emotion and internal states. In
      order to contribute to this debate, we investigated the semantic content of
      abstract concepts using a property generation task. Participants were asked to
      generate properties for 296 abstract concepts, which are relevant for
      constituting their meaning. These properties were categorized by a coding-scheme
      making a classification into modality-specific and verbal contents possible.
      Words were additionally rated with regard to concreteness/abstractness and
      familiarity. To identify possible subgroups of abstract concepts with distinct
      profiles of generated features, hierarchical cluster analyses were conducted.
      Participants generated a substantial proportion of introspective, affective,
      social, sensory and motor-related properties, in addition to verbal associations.
      Cluster analyses revealed different subcategories of abstract concepts, which can
      be characterized by the dominance of certain conceptual features. The present
      results are therefore compatible with grounded cognition theories, which
      emphasize the importance of linguistic, social, introspective and affective
      experiential information for the representation of abstract concepts. Our
      findings also indicate that abstract concepts are highly heterogeneous requiring
      the investigation of well-specified subcategories of abstract concepts, for
      instance as revealed by the present cluster analyses. The present study could
      thus guide future behavioral or imaging work further elucidating the
      representation of abstract concepts.

PMID- 30283391
TI  - The Role of Talent Management Comparing Medium-Sized and Large Companies - Major
      Challenges in Attracting and Retaining Talented Employees.
AB  - In order for companies to realize their organizational visions, they need staff
      who are high-potential and looking toward the future. Due to the demographic,
      social and economic situation in Europe, the labor market is already reflecting a
      lack of high-quality human resources (HR), which inspires research into and
      planned management of high-potential, i.e., talented, employees. Companies are
      aware that only those organizations that recognize this area as crucial and
      invest resources into it will be successful in the "war for talent." The purpose
      of the study was to research the field of talent management from the perspective
      of the definition of what the talent management process means for companies, how
      to attract and recognize talented employees, what development activities to
      provide them with and how to measure their performance and progress. We employed
      an exploratory approach, using the method of semi-structured interviews to gather
      information from 21 HR professionals who work at medium-sized and large Slovenian
      companies. We found that these organizations use various approaches and
      activities to attract and develop talented employees. At two thirds of the
      companies, performance is measured using annual evaluation interviews, by
      measuring the meeting of targets and evaluations by superiors. The biggest
      challenges in the field are attracting talented employees and positioning the
      organization as a desirable employer. The study is useful primarily as an
      overview of the field and of best practices, which companies can use to argument
      their existing processes.

PMID- 30283390
TI  - Perceptual Restoration of Temporally Distorted Speech in L1 vs. L2: Local Time
      Reversal and Modulation Filtering.
AB  - Speech is intelligible even when the temporal envelope of speech is distorted.
      The current study investigates how native and non-native speakers perceptually
      restore temporally distorted speech. Participants were native English speakers
      (NS), and native Japanese speakers who spoke English as a second language (NNS).
      In Experiment 1, participants listened to "locally time-reversed speech" where
      every x-ms of speech signal was reversed on the temporal axis. Here, the local
      time reversal shifted the constituents of the speech signal forward or backward
      from the original position, and the amplitude envelope of speech was altered as a
      function of reversed segment length. In Experiment 2, participants listened to
      "modulation-filtered speech" where the modulation frequency components of speech
      were low-pass filtered at a particular cut-off frequency. Here, the temporal
      envelope of speech was altered as a function of cut-off frequency. The results
      suggest that speech becomes gradually unintelligible as the length of reversed
      segments increases (Experiment 1), and as a lower cut-off frequency is imposed
      (Experiment 2). Both experiments exhibit the equivalent level of speech
      intelligibility across six levels of degradation for native and non-native
      speakers respectively, which poses a question whether the regular occurrence of
      local time reversal can be discussed in the modulation frequency domain, by
      simply converting the length of reversed segments (ms) into frequency (Hz).

PMID- 30283392
TI  - Preschoolers Favor Their Ingroup When Resources Are Limited.
AB  - The present study examined how 2- to 4-year-old preschoolers in Singapore (N =
      202) balance fairness and ingroup loyalty in resource distribution. Specifically,
      we investigated whether children would enact fair distributions as defined by an
      equality rule, or show partiality toward their ingroup when distributing
      resources, and the conditions under which one distributive strategy may take
      precedence over the other. In Experiment 1, children distributed four different
      pairs of toys between two puppets. In the Group condition, one puppet was
      assigned to the same group as the child while the other puppet was assigned to a
      different group using colored stickers in the No Group condition, no group
      assignments were made. Children's distributions were assessed for whether the
      toys were fairly (equally) distributed or unfairly (unequally) distributed in
      favor of either puppet. Experiment 2 was identical to the Group condition in
      Experiment 1, except that a third identical toy was introduced following the
      distribution of each toy pair. Distributions were separately assessed for whether
      the first two toys were fairly (equally) distributed or unfairly (unequally)
      distributed in favor of either puppet, and whether children distributed the third
      toy to the ingroup or outgroup puppet. Overall, the vast majority of children
      abided by an equality rule when resources were precisely enough to be shared
      between recipients, but distributed favorably to the ingroup member when there
      was limited resource availability. We found that fairness trumped ingroup loyalty
      except in resource distribution involving limited resources. Our results are
      consistent with findings from other resource distribution studies with
      preschoolers and similar studies measuring young infants' expectations of
      distributive behaviors in third-party observations. Taken together, there is
      evidence suggesting stability in the development of knowledge to behavior in the
      subdomains of fairness and ingroup loyalty.

PMID- 30283393
TI  - Longitudinal Task-Related Functional Connectivity Changes Predict Reading
      Development.
AB  - Longitudinal studies suggest developmentally dependent changes in lexical
      processing during reading development, implying a change in inter-regional
      functional connectivity over this period. The current study used functional
      magnetic resonance imaging (fMRI) to explore developmental changes in functional
      connectivity across multiple runs of a rhyming judgment task in young readers (8
      14 years) over an average 2.5-year span. Changes in functional segregation are
      correlated with and predict changes in the skill with which typically developing
      children learn to apply the alphabetic principle, as measured by pseudoword
      decoding. This indicates a developmental shift in the proportion of specialized
      functional clusters is associated with changes in reading skill and suggests a
      dependency of reading development on changes of particular neural pathways,
      specifically decreases in transitivity is indicative of greater network
      integration. This work provides evidence that characteristics of these pathways,
      quantified using graph-theoretic metrics, can be used to predict individual
      differences in reading development.

PMID- 30283394
TI  - Shyness and Learning Adjustment in Senior High School Students: Mediating Roles
      of Goal Orientation and Academic Help Seeking.
AB  - Learning maladjustment is a common phenomenon in the context of examination
      oriented education system in china, especially among high school students who
      experience intense pressure when preparing for the national college entrance
      examination. Previous literature suggests that shyness may negatively affect
      ones' cognition, emotion, and behavioral performance and lead to academic and
      social maladjustment. Therefore, learning adjustment among shy high school
      students is a critical and practical point of inquiry. With a sample of 677
      Chinese senior high school students, this study aims to assess the association
      between shyness and learning adjustment and related mechanisms of goal
      orientation (i.e., mastery-approach goals, mastery-avoid goals, performance
      approach goals, and performance-avoid goals) and academic help seeking (i.e.,
      instrumental help seeking from teacher, instrumental help seeking from classmate,
      executive help seeking, and avoidance of help seeking). Self-report measures were
      adopted to collect information on: demographic characteristics, the level of
      shyness, goal orientation, academic help seeking, and learning adjustment.
      Results indicated that shyness was negatively correlated with learning
      adjustment, and this association was mediated by the dimensions of goal
      orientation and dimensions of academic help seeking. Specifically, shyness not
      only predicted learning adjustment through mastery-approach goals, and
      instrumental help seeking (teachers) but also predicted learning adjustment
      through the multiple mediating effects of the dimensions of goal orientation and
      the dimensions of academic help seeking (i.e., mastery-approach goals and
      instrumental help seeking from teachers, mastery-approach goals and executive
      help seeking, mastery-avoid goals and instrumental help seeking from classmates,
      mastery-avoid goals and executive help seeking, and performance-avoid goals and
      executive help seeking). Identifying these mediators further enables us to work
      out effective measures to promote shy high school students' learning adjustment.

PMID- 30283396
TI  - Editorial: NEUROTRAUMA: From Emergency Room to Back to Day-by-Day Life.

PMID- 30283395
TI  - Biomarkers of Neurodegeneration in Autoimmune-Mediated Encephalitis.
AB  - Progranulin (PGRN), Total-Tau (t-tau), and Neurofilament light chain (NfL) are
      well known biomarkers of neurodegeneration. The objective of the present study
      was to investigate whether these parameters represent also biomarkers in
      autoimmune-mediated Encephalitis (AE) and may give us insights into the
      pathomechanisms of AE. We retrospectively examined the concentration of PGRN in
      the cerebrospinal fluid (CSF) and serum of 38 patients suffering from AE in acute
      phase and/or under treatment. This AE cohort comprises patients with
      autoantibodies against: NMDAR (n = 18 patients), Caspr2 (n = 8), Lgi-1 (n = 10),
      GABAB(R) (n = 1), and AMPAR (n = 1). Additionally, the concentrations of NfL (n =
      25) and t-tau (n = 13) in CSF were measured when possible. Follow up data
      including MRI were available in 13 patients. Several age-matched cohorts with
      neurological diseases besides neuroinflammation or neurodegeneration served as
      control groups. We observed that PGRN was significantly elevated in the CSF of
      patients with NMDAR-AE in the acute phase, but normalized at follow up under
      treatment (p < 0.01). In the CSF of other patients with AE PGRN was in the range
      of the CSF levels of control groups. T-tau was highly elevated in the CSF of
      patients with temporal FLAIR-signal in the MRI and in patients developing a
      hippocampal sclerosis. NfL was exceptionally high initially in Patients with AE
      with a paraneoplastic or parainfectious cause and also normalized under
      treatment. The normalizations of all biomarkers were mirrored in an improvement
      on the modified Rankin scale. The data suggest that the concentration of PGRN in
      CSF might be a biomarker for acute NMDAR-AE. Pathological high t-tau levels may
      indicate a risk for hippocampal sclerosis. The biomarker properties of NfL remain
      unclear since the levels decrease under treatment, but it could not predict
      severity of disease in this small cohort. According to our results, we recommend
      to measure in clinical practice PGRN and t-tau in the CSF of patients with AE.

PMID- 30283397
TI  - Segmentation of Peripheral Nerves From Magnetic Resonance Neurography: A Fully
      Automatic, Deep Learning-Based Approach.
AB  - Diagnosis of peripheral neuropathies relies on neurological examinations,
      electrodiagnostic studies, and since recently magnetic resonance neurography
      (MRN). The aim of this study was to develop and evaluate a fully-automatic
      segmentation method of peripheral nerves of the thigh. T2-weighted sequences
      without fat suppression acquired on a 3 T MR scanner were retrospectively
      analyzed in 10 healthy volunteers and 42 patients suffering from clinically and
      electrophysiologically diagnosed sciatic neuropathy. A fully-convolutional neural
      network was developed to segment the MRN images into peripheral nerve and
      background tissues. The performance of the method was compared to manual inter
      rater segmentation variability. The proposed method yielded Dice coefficients of
      0.859 +/- 0.061 and 0.719 +/- 0.128, Hausdorff distances of 13.9 +/- 26.6 and
      12.4 +/- 12.1 mm, and volumetric similarities of 0.930 +/- 0.054 and 0.897 +/-
      0.109, for the healthy volunteer and patient cohorts, respectively. The complete
      segmentation process requires less than one second, which is a significant
      decrease to manual segmentation with an average duration of 19 +/- 8 min.
      Considering cross-sectional area or signal intensity of the segmented nerves,
      focal and extended lesions might be detected. Such analyses could be used as
      biomarker for lesion burden, or serve as volume of interest for further
      quantitative MRN techniques. We demonstrated that fully-automatic segmentation of
      healthy and neuropathic sciatic nerves can be performed from standard MRN images
      with good accuracy and in a clinically feasible time.

PMID- 30283398
TI  - Modulation of Cognitive and Emotional Control in Age-Related Mild-to-Moderate
      Hearing Loss.
AB  - Progressive hearing loss is a common phenomenon in healthy aging and may affect
      the perception of emotions expressed in speech. Elderly with mild to moderate
      hearing loss often rate emotional expressions as less emotional and display
      reduced activity in emotion-sensitive brain areas (e.g., amygdala). However, it
      is not clear how hearing loss affects cognitive and emotional control mechanisms
      engaged in multimodal speech processing. In previous work we showed that
      negative, task-relevant and -irrelevant emotion modulates the two types of
      control in younger and older adults without hearing loss. To further explore how
      reduced hearing capacity affects emotional and cognitive control, we tested
      whether moderate hearing loss (>30 dB) at frequencies relevant for speech impacts
      cognitive and emotional control. We tested two groups of older adults with
      hearing loss (HL; N = 21; mean age = 70.5) and without hearing loss (NH; N = 21;
      mean age = 68.4). In two EEG experiments participants observed multimodal video
      clips and either categorized pronounced vowels (cognitive conflict) or their
      emotions (emotional conflict). Importantly, the facial expressions were either
      matched or mismatched with the corresponding vocalizations. In both conflict
      tasks, we found that negative stimuli modulated behavioral conflict processing in
      the NH but not the HL group, while the HL group performed at chance level in the
      emotional conflict task. Further, we found that the amplitude difference between
      congruent and incongruent stimuli was larger in negative relative to neutral N100
      responses across tasks and groups. Lastly, in the emotional conflict task,
      neutral stimuli elicited a smaller N200 response than emotional stimuli primarily
      in the HL group. Consequently, age-related hearing loss not only affects the
      processing of emotional acoustic cues but also alters the behavioral benefits of
      emotional stimuli on cognitive and emotional control, despite preserved early
      neural responses. The resulting difficulties in the multimodal integration of
      incongruent emotional stimuli may lead to problems in processing complex social
      information (irony, sarcasm) and impact emotion processing in the limbic network.
      This could be related to social isolation and depression observed in the elderly
      with age-related hearing loss.

PMID- 30283399
TI  - Characterization of NGFFYamide Signaling in Starfish Reveals Roles in Regulation
      of Feeding Behavior and Locomotory Systems.
AB  - Neuropeptides in deuterostomian invertebrates that have an Asn-Gly motif (NG
      peptides) have been identified as orthologs of vertebrate neuropeptide-S (NPS)
      type peptides and protostomian crustacean cardioactive peptide (CCAP)-type
      neuropeptides. To obtain new insights into the physiological roles of NG peptides
      in deuterostomian invertebrates, here we have characterized the NG peptide
      signaling system in an echinoderm-the starfish Asterias rubens. The neuropeptide
      NGFFYamide was identified as the ligand for an A. rubens NPS/CCAP-type receptor,
      providing further confirmation that NG peptides are orthologs of NPS/CCAP-type
      neuropeptides. Using mRNA in situ hybridization, cells expressing the NGFFYamide
      precursor transcript were revealed in the radial nerve cords, circumoral nerve
      ring, coelomic epithelium, apical muscle, body wall, stomach, and tube feet of A.
      rubens, indicating that NGFFYamide may have a variety of physiological roles in
      starfish. One of the most remarkable aspects of starfish biology is their feeding
      behavior, where the stomach is everted out of the mouth over the soft tissue of
      prey. Previously, we reported that NGFFYamide triggers retraction of the everted
      stomach in A. rubens and here we show that in vivo injection of NGFFYamide causes
      a significant delay in the onset of feeding on prey. To investigate roles in
      regulating other aspects of starfish physiology, we examined the in vitro effects
      of NGFFYamide and found that it causes relaxation of acetylcholine-contracted
      apical muscle preparations and induction of tonic and phasic contraction of tube
      feet. Furthermore, analysis of the effects of in vivo injection of NGFFYamide on
      starfish locomotor activity revealed that it causes a significant reduction in
      mean velocity and distance traveled. Interestingly, experimental studies on
      mammals have revealed that NPS is an anxiolytic that suppresses appetite and
      induces hyperactivity in mammals. Our characterization of the actions of
      NGFFYamide in starfish indicates that NPS/NG peptide/CCAP-type signaling is an
      evolutionarily ancient regulator of feeding and locomotion.

PMID- 30283401
TI  - Expression and Functional Analysis of the BCL2-Associated Agonist of Cell Death
      (BAD) Gene in the Sheep Ovary During the Reproductive Cycle.
AB  - Most ewes in China are seasonally polyestrous with normal ovulatory cycles, which
      is controlled by photoperiod (length of the daily light phase). These ewes are
      estrous in the short-day season and anestrus in the long-day season and cannot
      mate during anestrus. Thus seasonal breeding limits both diversification and
      intensification of production. If sheep can estrus all round year, it can be
      mated twice per year, which can greatly improve the economic benefits. To change
      seasonal estrus at the genetic level and cultivating new sheep breeds, it is
      important to understand the molecular mechanisms of seasonal breeding trait in
      sheep. The BCL2-associated agonist of cell death (BAD) gene being a regulator of
      cellular apoptosis was identified by our previous RNA-Seq, which is associated
      with follicular development in mammalian ovaries. However, the mechanism how BAD
      can regulate estrus in sheep was poorly understood. In this study, we
      characterized ovine BAD, including full-length mRNA cloning and protein sequence
      prediction, as well as BAD expression profile in Small-tailed Han (STH) sheep.
      The highest expression levels of BAD were observed in sheep hypothalamus, lung,
      and pituitary, while the lowest expression was in liver. Functional analysis of
      BAD was performed in primary granulosa cells of sheep. The concentration of P4
      was significantly increased after RNAi interference of BAD, while P4 level was
      shown to be opposite after BAD overexpression in vitro. It has been found that
      BAD can reduce progesterone levels by promoting ovarian GC apoptosis, which might
      be involved in regulating the estrus cycle in sheep.

PMID- 30283402
TI  - Chemistry and Hypoglycemic Activity of GPR119 Agonist ZB-16.
AB  - This article is to highlight the chemical properties and primary pharmacology of
      novel GPR119 agonist ZB-16 and its analogs, which were rejected during the
      screening. Experiments were performed in vitro (specific activity, metabolism and
      cell toxicity) and in vivo (hypoglycemic activity and pharmacokinetics). ZB-16
      exhibits nanomolar activity (EC50 = 7.3-9.7 nM) on target receptor GPR119 in
      vitro associated with hypoglycemic activity in vivo. In animals with
      streptozotocin-nicotinamide induced type 2 diabetes mellitus (STZ-NA T2D) daily
      oral dose of ZB-16 (1 mg/kg) or sitagliptin (10 mg/kg) for 28 days resulted in
      the reduction of blood glucose levels. The effects of ZB-16 were comparable to
      the hypoglycemic action of sitagliptin. ZB-16 demonstrated relatively low plasma
      exposition, high distribution volume, mild clearance and a prolonged half-life
      (more than 12 h). The present study demonstrates that the targeted search for
      selective GPR119 receptor agonists is a well-founded approach for developing
      novel drugs for the therapy of T2D. Based on the combination of high in vitro
      activity (compared to competitor standards), a useful ADME profile, distinct
      hypoglycemic activity which is comparable to the efficacy of sitagliptin in rats
      with experimental T2D, and the acceptable pharmacokinetic profile, we recommend
      the ZB-16 compound for further research.

PMID- 30283403
TI  - Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized
      Placebo-Controlled Clinical Trial.
AB  - Purpose: To explore in a small pilot study whether oral melatonin, administered
      during ovarian stimulation increases clinical pregnancy rate (CPR) after IVF and
      what dose might be most effective. Methods: Pilot double-blind, dose-finding,
      placebo-controlled randomized clinical trial in private IVF clinics in Australia
      between September 2014 and September 2016. One hundred and sixty women having
      their first cycle of IVF or ICSI were randomized to receive placebo (n = 40),
      melatonin 2 mg (n = 41), melatonin 4 mg (n = 39), or melatonin 8 mg (n = 40)
      twice per day (BD) during ovarian stimulation. The primary outcome was CPR.
      Secondary outcomes included serum and follicular fluid (FF) melatonin
      concentrations, oocyte/embryo quantity/quality, and live birth rate (LBR).
      Analysis was performed using the intention-to-treat principle. Results: There was
      no difference in CPR or LBR between any of the four groups (p = 0.5). When all
      the doses of melatonin were compared as a group with placebo, the CPR was 21.7%
      for the former and 15.0% for the latter [OR 1.57 (95% CI 0.59, 4.14), p = 0.4].
      There were also no differences between the groups in total oocyte number, number
      of MII oocytes, number of fertilized oocytes, or the number or quality of embryos
      between the groups. This is despite mean FF melatonin concentration in the
      highest dose group (8 mg BD) being nine-fold higher compared with placebo (P <
      0.001). Conclusion: No significant differences were observed in CPR or oocyte and
      embryo parameters despite finding a nine-fold increase in FF melatonin
      concentration. However, this study was not sufficiently powered to assess
      differences in CPR and therefore, these results should be interpreted with
      caution. Because this was a small RCT, a beneficial effect of melatonin on IVF
      pregnancy rates cannot be excluded and merits confirmation in further, larger
      clinical trials. ANZCTR (http://www.anzctr.org.au/ Project ID:
      ACTRN12613001317785).

PMID- 30283405
TI  - Hypothalamic Proopiomelanocortin Is Necessary for Normal Glucose Homeostasis in
      Female Mice.
AB  - The arcuate nucleus of the hypothalamus is a key regulator of energy balance and
      glucose homeostasis. In particular, arcuate proopiomelanocortin (POMC) neurons
      inhibit food intake, stimulate energy expenditure and increase glucose tolerance.
      The interruption of insulin or glucose signaling in POMC neurons leads to glucose
      intolerance without changing energy homeostasis. Although it was previously shown
      that POMC neurons are necessary for normal glucose homeostasis, the participation
      of POMC neuropeptide, by mechanisms independent of energy balance, remains to be
      demonstrated. To study the role of POMC in the regulation of glucose homeostasis,
      we performed glucose and insulin tolerance tests in non-obese mice lacking
      hypothalamic POMC expression. We found that POMC deficiency leads to glucose
      intolerance and insulin resistance in female mice before the onset of obesity or
      hyperphagia. Conversely, POMC deficiency does not impair glucose homeostasis in
      non-obese male mice. Interestingly, females completely normalize both glucose and
      insulin tolerance after genetic POMC restoration. Next, to further study sex
      dimorphism of POMC neurons regarding glucose homeostasis, we measured glucose
      elicited changes in C-FOS by performing immunofluorescence in brain slices of
      POMC-EGFP mice. Remarkably, we found that glucose-induced C-FOS expression in
      POMC neurons is more than 3-fold higher in female than in male mice. Altogether,
      our results reveal a key role of arcuate POMC in the regulation of glucose
      homeostasis in females. Since POMC reactivation completely reverses the
      diabetogenic phenotype, arcuate POMC could be a potential target for diabetes
      therapy.

PMID- 30283400
TI  - Sterol Metabolism and Transport in Atherosclerosis and Cancer.
AB  - Cholesterol is a vital lipid molecule for mammalian cells, regulating fluidity of
      biological membranes, and serving as an essential constituent of lipid rafts.
      Mammalian cells acquire cholesterol from extracellular lipoproteins and from de
      novo synthesis. Cholesterol biosynthesis generates various precursor sterols.
      Cholesterol undergoes metabolic conversion into oxygenated sterols (oxysterols),
      bile acids, and steroid hormones. Cholesterol intermediates and metabolites have
      diverse and important cellular functions. A network of molecular machineries
      including transcription factors, protein modifiers, sterol transporters/carriers,
      and sterol sensors regulate sterol homeostasis in mammalian cells and tissues.
      Dysfunction in metabolism and transport of cholesterol, sterol intermediates, and
      oxysterols occurs in various pathophysiological settings such as atherosclerosis,
      cancers, and neurodegenerative diseases. Here we review the cholesterol,
      intermediate sterol, and oxysterol regulatory mechanisms and intracellular
      transport machineries, and discuss the roles of sterols and sterol metabolism in
      human diseases.

PMID- 30283406
TI  - Combination of a Latency-Reversing Agent With a Smac Mimetic Minimizes Secondary
      HIV-1 Infection in vitro.
AB  - Latency-reversing agents (LRAs) are considered a potential tool to cure human
      immunodeficiency virus type 1 (HIV-1) infection, but when they are taken alone,
      virus production by reactivated cells and subsequent infection will occur. Hence,
      it is crucial to simultaneously take appropriate measures to prevent such
      secondary HIV-1 infection. In this regard, a strategy to minimize the production
      of infectious viruses from LRA-reactivated cells is worth pursuing. Here, we
      focused on a second mitochondria-derived activator of caspases (Smac) mimetic,
      birinapant, to induce apoptosis in latent HIV-1-infected cells. When birinapant
      was administered alone, it only slightly increased the expression of caspase-3.
      However, in combination with an LRA (e.g., PEP005), it strongly induced the
      expression of caspase-3 followed by enhanced apoptosis. Importantly, the
      combination eliminated reactivated cells and drastically reduced HIV-1
      production. Finally, we found that birinapant decreased the mRNA expression of
      HIV-1 that was induced by PEP005 in the primary CD4+ T-cells from HIV-1-carrying
      patients as well. These results suggest that the combination of an LRA and an
      "apoptosis-inducing" agent, such as a Smac mimetic, is a possible treatment
      option to decrease HIV-1 reservoirs without the occurrence of HIV-1 production by
      reactivated cells.

PMID- 30283407
TI  - Small Antimicrobial Resistance Plasmids in Livestock-Associated Methicillin
      Resistant Staphylococcus aureus CC398.
AB  - Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA)
      isolates of the clonal complex 398 are often resistant to a number of
      antimicrobial agents. Studies on the genetic basis of antimicrobial resistance in
      these bacteria identified SCCmec cassettes, various transposons and plasmids of
      different sizes that harbor antimicrobial resistance genes. While large plasmids
      that carry multiple antimicrobial resistance genes - occasionally together with
      heavy metal resistance genes and/or virulence genes - are frequently seen in LA
      MRSA ST398, certain resistance genes are also associated with small plasmids of
      up to 15 kb in size. These small resistance plasmids usually carry only one, but
      in rare cases also two or three antimicrobial resistance genes. In the current
      review, we focus on small plasmids that carry the macrolide-lincosamide
      streptogramin B resistance genes erm(C) or erm(T), the lincosamide resistance
      gene lnu(A), the pleuromutilin-lincosamide-streptogramin A resistance genes
      vga(A) or vga(C), the spectinomycin resistance gene spd, the apramycin resistance
      gene apmA, or the trimethoprim resistance gene dfrK. The detailed analysis of the
      structure of these plasmids allows comparisons with similar plasmids found in
      other staphylococci and underlines in many cases an exchange of such plasmids
      between LA-MRSA ST398 and other staphylococci including also coagulase-negative
      staphylococci.

PMID- 30283408
TI  - Abundant and Rare Microbial Biospheres Respond Differently to Environmental and
      Spatial Factors in Tibetan Hot Springs.
AB  - Little is known about the distribution and ecological functions of abundant,
      intermediate, and rare biospheres and their correlations with environmental
      factors in hot springs. Here, we explored the microbial community composition of
      total, abundant, intermediate, and rare biospheres in 66 Tibetan hot springs
      (pairwise geographic distance 0-610 km, temperature 32-86 degrees C, pH 3.0-9.5,
      and salinity 0.13-1.32 g/L) with the use of Illumina MiSeq high-throughput
      sequencing. The results showed that the abundant sub-communities were mainly
      composed of Chloroflexi, Proteobacteria, Deinococcus-Thermus, Aquificae,
      Bacteroidetes, and Firmicutes. In contrast, the rare sub-communities mainly
      consisted of most newly proposed or candidate phyla of Dictyoglomi,
      Hydrogenedentes, Atribacteria, Hadesarchaea, Aminicenantes, Microgenomates,
      Calescamantes, Omnitrophica, Altiarchaeales, and Chlamydiae. However, the
      abundant and rare sub-communities shared some common phyla (e.g., Crenarchaeota,
      Bathyarchaeota, and Chlorobi), which were composed of different OTUs. The
      abundant, intermediate, and rare sub-communities were mainly influenced by
      different environmental variables, which could be ascribed to the fact that they
      may have different growth and activity and thus respond differently to these
      variables. Spatial factors showed more contribution to shaping of the
      intermediate and rare communities than to abundant sub-community, suggesting that
      the abundant taxa were more easily dispersed than their rare counterparts among
      hot springs. Microbial ecological function prediction revealed that the abundant
      and rare sub-communities responded differently to the measured environmental
      factors, suggesting they may occupy different ecological niches in hot springs.
      The rare sub-communities may play more important roles in organic matter
      degradation than their abundant counterparts in hot springs. Collectively, this
      study provides a better understanding on the microbial community structure and
      potential ecological functions of the abundant and rare biospheres in hot spring
      ecosystems. The identified rare taxa provide new opportunities of ecological,
      taxonomic and genomic discoveries in Tibetan hot springs.

PMID- 30283409
TI  - Global Marine N2 Fixation Estimates: From Observations to Models.
AB  - Fixed nitrogen (N) limits productivity across much of the low-latitude ocean. The
      magnitude of its inventory results from the balance of N input and N loss, the
      latter largely occurring in regionally well-defined low-oxygen waters and
      sediments (denitrification and anammox). The rate and distribution of N input by
      biotic N2 fixation, the dominant N source, is not well known. Here we compile N2
      fixation estimates from experimental measurements, tracer-based geochemical and
      modeling approaches, and discuss their limitations and uncertainties. The lack of
      adequate experimental data coverage and the insufficient understanding of the
      controls of marine N2 fixation result in high uncertainties, which make the
      assessment of the current N-balance a challenge. We suggest that a more
      comprehensive understanding of the environmental and ecological interaction of
      marine N2 fixers is required to advance the field toward robust N2 fixation rates
      estimates and predictions.

PMID- 30283404
TI  - The Gut-Kidney Axis: Putative Interconnections Between Gastrointestinal and Renal
      Disorders.
AB  - Diabetic kidney disease (DKD) is a devastating condition associated with
      increased morbidity and premature mortality. The etiology of DKD is still largely
      unknown. However, the risk of DKD development and progression is most likely
      modulated by a combination of genetic and environmental factors. Patients with
      autoimmune diseases, like type 1 diabetes, inflammatory bowel disease, and celiac
      disease, share some genetic background. Furthermore, gastrointestinal disorders
      are associated with an increased risk of kidney disease, although the true
      mechanisms have still to be elucidated. Therefore, the principal aim of this
      review is to evaluate the impact of disturbances in the gastrointestinal tract on
      the development of renal disorders.

PMID- 30283411
TI  - Molecular Epidemiology of Photobacterium damselae subsp. damselae Outbreaks in
      Marine Rainbow Trout Farms Reveals Extensive Horizontal Gene Transfer and High
      Genetic Diversity.
AB  - The marine bacterium Photobacterium damselae subsp. damselae is a pathogen for a
      variety of marine animals, as well as for humans, and is nowadays considered an
      emerging pathogen for fish of importance in marine aquaculture. Recent studies
      have suggested that outbreaks in fish farms are caused by multiclonal populations
      of this subspecies that exist in the environment. Here, we report the study of a
      collection of 31 strains isolated during the course of disease outbreaks in
      marine rainbow trout farms in Denmark in 1994, 1995, and 2006, respectively. A
      phylogenetic analysis based on the toxR gene sequence, and the screening of
      virulence-related genes uncovered a high genetic heterogeneity, even among
      strains isolated from the same fish farm at the same time. Moreover, comparative
      analysis of the whole genome sequences of four selected strains revealed a large
      number of differentially occurring genes, which included virulence genes, pPHDD1
      plasmid, polysaccharide synthesis gene clusters, CRISPR-Cas systems and putative
      new mobile genetic elements. This study provides sound evidence that P. damselae
      subsp. damselae outbreaks in Danish rainbow trout farms were caused by
      multiclonal populations and that horizontal gene transfer constitutes a strong
      driving force in the generation of intraspecific diversity in this pathogen.

PMID- 30283410
TI  - Diet, Microbiota and Gut-Lung Connection.
AB  - The gut microbial community (Gut microbiota) is known to impact metabolic
      functions as well as immune responses in our body. Diet plays an important role
      in determining the composition of the gut microbiota. Gut microbes help in
      assimilating dietary nutrients which are indigestible by humans. The metabolites
      produced by them not only modulate gastro-intestinal immunity, but also impact
      distal organs like lung and brain. Micro-aspiration of gut bacteria or movement
      of sensitized immune cells through lymph or bloodstream can also influence immune
      response of other organs. Dysbiosis in gut microbiota has been implicated in
      several lung diseases, including allergy, asthma and cystic fibrosis. The bi
      directional cross-talk between gut and lung (termed as Gut-Lung axis) is best
      exemplified by intestinal disturbances observed in lung diseases. Some of the
      existing probiotics show beneficial effects on lung health. A deeper
      understanding of the gut microbiome which comprises of all the genetic material
      within the gut microbiota and its role in respiratory disorders is likely to help
      in designing appropriate probiotic cocktails for therapeutic applications.

PMID- 30283412
TI  - Identification and Expression Analysis of an Atypical Alkaline Phosphatase in
      Emiliania huxleyi.
AB  - Emiliania huxleyi, a cosmopolitan coccolithophore in the modern ocean, plays an
      important role in the carbon cycle and local climate feedback as it can form
      extensive blooms, calcify, and produce dimethylsulfoniopropionate (DMSP) leading
      to the generation of dimethyl sulfide (DMS) which affects climate when oxidized
      in the atmosphere. It is known to be able to utilize dissolved organic phosphorus
      (DOP) by expressing a specific type of alkaline phosphatase (EHAP1) under
      phosphorus-limited conditions. In this study, we identified a new alkaline
      phosphatase (EH-PhoAaty) in this species, which we found belongs to the newly
      classified PhoAaty family. The expression of this atypical phosphatase was up
      regulated under P-depleted conditions at both the transcriptional and
      translational levels, suggesting that E. huxleyi is able to express this AP to
      cope with phosphorus limitation. Comparative analysis revealed different
      transcriptional expression dynamics between eh-PhoA aty and ehap1, although both
      genes exhibited inducible expression under phosphate deficiency. In addition,
      after AP activity was eliminated by using EDTA to chelate metal ions, we found
      that AP activity was recovered with the supplement of Ca2+ and Zn2+, indicative
      of the adoption of Ca2+ as the cofactor under Zn-P co-limited conditions, likely
      a result of adaptation to oceanic environments where Zn2+ is often limiting.

PMID- 30283413
TI  - A GRX1 Promoter Variant Confers Constitutive Noisy Bimodal Expression That
      Increases Oxidative Stress Resistance in Yeast.
AB  - Higher noise in the expression of stress-related genes was previously shown to
      confer better resistance in selective conditions. Thus, evolving the promoter of
      such genes toward higher transcriptional noise appears to be an attractive
      strategy to engineer microbial strains with enhanced stress resistance. Here we
      generated hundreds of promoter variants of the GRX1 gene involved in oxidative
      stress resistance in Saccharomyces cerevisiae and created a yeast library by
      replacing the native GRX1 promoter by these variants at the native locus. An
      outlier clone with very strong increase in noise (6-times) at the same mean
      expression level as the native strain was identified whereas the other noisiest
      clones were only 3-times increased. This variant provides constitutive bimodal
      expression and consists in 3 repeated but differently mutated copies of the GRX1
      promoter. In spite of the multi-factorial oxidative stress-response in yeast,
      replacement of the native promoter by this variant is sufficient alone to confer
      strongly enhanced resistance to H2O2 and cumene hydroperoxide. New replacement of
      this variant by the native promoter in the resistant strain suppresses the
      resistance. This work shows that increasing noise of target genes in a relevant
      strategy to engineer microbial strains toward better stress resistance. Multiple
      promoter replacement could synergize the effect observed here with the sole GRX1
      promoter replacement. Finally this work suggests that combining several mutated
      copies of the target promoter could allow enhancing transcriptional-mediated
      noise at higher levels than mutating a single copy by providing constitutive
      bimodal and highly heterogeneous expression distribution.

PMID- 30283415
TI  - Relative Level of Bacteriophage Multiplication in vitro or in Phyllosphere May
      Not Predict in planta Efficacy for Controlling Bacterial Leaf Spot on Tomato
      Caused by Xanthomonas perforans.
AB  - Following analysis of eight phages under in vitro, growth chamber and greenhouse
      conditions with the bacterial spot of tomato pathogen Xanthomonas perforans,
      there was no correlation between disease control efficacy and in vitro phage
      multiplication, in vitro bacterial suppression, or in vivo phage multiplication
      in the presence of the host, but there was a low correlation between phage
      persistence on the leaf surface and disease control. Two of the 8 virulent phages
      (PhiXv3-21 and PhiXp06-02) were selected for in depth analysis with two X.
      perforans (Xp06-2-1 and Xp17-12) strains. In in vitro experiments, phage PhiXv3
      21 was equally effective in infecting the two bacterial strains based on
      efficiency of plating (EOP). Phage PhiXp06-02, on the other hand, had a high EOP
      on strain Xp06-2-1 but a lower EOP on strain Xp17-12. In several growth chamber
      experiments, PhiXv3-21 was less effective than phage PhiXp06-02 in reducing
      disease caused by strain Xp06-2-1, but provided little or no disease control
      against strain Xp17-12. Interestingly, PhiXp06-02 could multiply to significantly
      higher levels on the tomato leaf surface than phage PhiXv3-21. The leaf surface
      appears to be important in terms of the ability of certain bacteriophages to
      multiply in the presence of the bacterial host. PhiXv3-21, when applied to
      grapefruit leaves in combination with a bacterial host, was unable to multiply to
      high levels, whereas on tomato leaflets the phage multiplied exponentially. One
      plausible explanation is that the leaf surface may be an important factor for
      attachment of certain phages to their bacterial host.

PMID- 30283414
TI  - Scrophularia striata Extract Supports Rumen Fermentation and Improves Microbial
      Diversity in vitro Compared to Monensin.
AB  - In the search for natural alternatives to antibiotic feed additives, we compared
      the efficacy of two doses of Scrophularia striata extract [S. striata-Low at 40
      and S. striata-High at 80 mg g-1 dry matter (DM)] with monensin (monensin) and a
      negative control in the modulation of rumen fermentation, methane production and
      microbial abundance in vitro. Microbes were investigated using qPCR and 16S rRNA
      targeted sequencing. Data showed that the addition of S. striata increased
      production of total short chain fatty acids (SCFA) in comparison to both monensin
      and control (P = 0.04). The addition of S. striata increased acetate production,
      and increased propionate at the higher dosage (P < 0.001). Supplementation of S.
      striata lowered methane production (P < 0.001) compared to control but with no
      effect compared to monensin. Ammonia concentration decreased by 52% (P < 0.001)
      with S. striata-High supplementation (4.14 mmol L-1) compared to control, which
      was greater than that of monensin (36%). The diversity of rumen bacteria was
      reduced (P < 0.001) for monensin and S. striata for both the number of observed
      OTUs and the Chao1 index. Quantitative analysis of Protozoa showed a decrease in
      the monensin treatment (P = 0.05) compared to control. Archaea copy numbers
      decreased equally in both S. striata-High and monensin treatments compared to the
      control group. Supplementation with S. striata increased relative abundances of
      Fibrobacteres (P < 0.001) and Planctomycetes (P = 0.001) in comparison to both
      the control and monensin treatments. Significant negative correlations were
      observed between the abundances of Bacteroides, Fusobacterium, and Succinivibrio
      genera and methane (r > -0.71; P <= 0.001). The abundance of Fibrobacter genera
      and total SCFA (r = 0.86), acetate (r = 0.75), and valerate (r = -0.51; P <
      0.001) correlated positively. These results suggest that S. striata
      supplementation at 80 mg g-1 DM inclusion, similar to monensin, supports rumen
      fermentation, lowers methane and ammonia production. However, S. striata
      supported rumen fermentation toward higher total SCFA and propionate production,
      while unlike monensin still supported a diverse rumen microbiome and an increase
      in cellulolytic bacteria such as Fibrobacter.

PMID- 30283416
TI  - FLIM-MAP: Gene Context Based Identification of Functional Modules in Bacterial
      Metabolic Pathways.
AB  - Prediction of functional potential of bacteria can only be ascertained by the
      accurate annotation of its metabolic pathways. Homology based methods decipher
      metabolic gene content but ignore the fact that homologs of same protein can
      function in different pathways. Therefore, mere presence of all constituent genes
      in an organism is not sufficient to indicate a pathway. Contextual occurrence of
      genes belonging to a pathway on the bacterial genome can hence be exploited for
      an accurate estimation of functional potential of a bacterium. In this
      communication, we present a novel annotation resource to accurately identify
      pathway presence by using gene context. Our tool FLIM-MAP (Functionally Important
      Modules in bacterial Metabolic Pathways) predicts biologically relevant
      functional units called 'GCMs' (Gene Context based Modules) from a given
      metabolic reaction network. We benchmark the accuracy of our tool on amino acids
      and carbohydrate metabolism pathways.

PMID- 30283417
TI  - Using 'Omic Approaches to Compare Temporal Bacterial Colonization of Lolium
      perenne, Lotus corniculatus, and Trifolium pratense in the Rumen.
AB  - Understanding rumen plant-microbe interactions is central for development of
      novel methodologies allowing improvements in ruminant nutrient use efficiency.
      This study investigated rumen bacterial colonization of fresh plant material and
      changes in plant chemistry over a period of 24 h period using three different
      fresh forages: Lolium perenne (perennial ryegrass; PRG), Lotus corniculatus
      (bird's foot trefoil; BFT) and Trifolium pratense (red clover; RC). We show using
      16S rRNA gene ion torrent sequencing that plant epiphytic populations present pre
      incubation (0 h) were substantially different to those attached post incubations
      in the presence of rumen fluid on all forages. Thereafter primary and secondary
      colonization events were evident as defined by changes in relative abundances of
      attached bacteria and changes in plant chemistry, as assessed using Fourier
      transform infrared (FTIR) spectroscopy. For PRG colonization, primary
      colonization occurred for up to 4 h and secondary colonization from 4 h onward.
      The changes from primary to secondary colonization occurred significantly later
      with BFT and RC, with primary colonization being up to 6 h and secondary
      colonization post 6 h of incubation. Across all 3 forages the main colonizing
      bacteria present at all time points post-incubation were Prevotella,
      Pseudobutyrivibrio, Ruminococcus, Olsenella, Butyrivibrio, and Anaeroplasma
      (14.2, 5.4, 1.9, 2.7, 1.8, and 2.0% on average respectively), with
      Pseudobutyrivibrio and Anaeroplasma having a higher relative abundance during
      secondary colonization. Using CowPI, we predict differences between bacterial
      metabolic function during primary and secondary colonization. Specifically, our
      results infer an increase in carbohydrate metabolism in the bacteria attached
      during secondary colonization, irrespective of forage type. The CowPI data
      coupled with the FTIR plant chemistry data suggest that attached bacterial
      function is similar irrespective of forage type, with the main changes occurring
      between primary and secondary colonization. These data suggest that the sward
      composition of pasture may have major implications for the temporal availability
      of nutrients for animal.

PMID- 30283418
TI  - Dosing Regimen of Enrofloxacin Impacts Intestinal Pharmacokinetics and the Fecal
      Microbiota in Steers.
AB  - Objective: The intestinal concentrations of antimicrobial drugs that select for
      resistance in fecal bacteria of cattle are poorly understood. Our objective was
      to associate active drug concentrations in the intestine of steers with changes
      in the resistance profile and composition of the fecal microbiome. Methods:
      Steers were administered either a single dose (12.5 mg/kg) or 3 multiple doses (5
      mg/kg) of enrofloxacin subcutaneously every 24 h. Enrofloxacin and ciprofloxacin
      concentrations in intestinal fluid were measured over 96 h, and the abundance and
      MIC of E. coli in culture and the composition of the fecal microbiota by 16S rRNA
      gene sequencing were assessed over 192 h after initial treatment. Results: Active
      drug concentrations in the ileum and colon exceeded plasma and interstitial fluid
      concentrations, but were largely eliminated by 48 h after the last dose. The
      concentration of E. coli in the feces significantly decreased during peak drug
      concentrations, but returned to baseline by 96 h in both groups. The median MIC
      of E. coli isolates increased for 24 h in the single dose group, and for 48 h in
      the multiple dose group. The median MIC was higher in the multiple dose group
      when compared to the single dose group starting 12 h after the initial dose. The
      diversity of the fecal microbiota did not change in either treatment group, and
      taxa-specific changes were primarily seen in phyla commonly associated with the
      rumen. Conclusions: Both dosing regimens of enrofloxacin achieve high
      concentrations in the intestinal lumen, and the rapid elimination mitigates long
      term impacts on fecal E. coli resistance and the microbiota.

PMID- 30283419
TI  - Changes in the Intestine Microbial, Digestive, and Immune-Related Genes of
      Litopenaeus vannamei in Response to Dietary Probiotic Clostridium butyricum
      Supplementation.
AB  - The intestine barrier serves as the front-line defense in shrimp. Clostridium
      butyricum (CB) can produce butyric acid that provides energy for the intestine
      epithelial cells of the host. However, the effects of dietary CB on the intestine
      microbiome and the digestion and immunity of the host is not clear. In this
      study, we therefore investigated the composition and metabolic activity of the
      intestine microbiome, and digestive and immune-related gene expression in
      Litopenaeus vannamei fed with diets containing different levels of CB: basal diet
      (control), 2.5 * 109 CFU kg-1 diet (CB1), 5.0 * 109 CFU kg-1 diet (CB2), and 1.0
      * 1010 CFU kg-1 diet (CB3) for 56 days. Dietary CB altered the composition of the
      intestine microbiome. Specifically, the dominant bacterial phylum Proteobacteria
      was enriched in the CB3 group and weakened in the CB1 and CB2 groups. The
      Bacteroidetes was enriched in the CB1 and CB2 groups and weakened in the CB3
      group. The Firmicutes was enriched in all three CB groups. At the genus level,
      the potential pathogen (Desulfovibrio and Desulfobulbus) were weakened, and
      beneficial bacteria (Bacillus, Clostridium, Lachmoclostridium, Lachnospiraceae,
      and Lactobacillus) were enriched in response to dietary CB; these might
      contribute to the expression of the host digestive genes (alpha-amylase, lipase,
      trypsin, fatty acid-binding protein, and fatty acid synthase) and immune-related
      genes (prophenoloxidase, lipopolysaccharide and beta-1,3-glucan binding protein,
      lysozyme, crustin, and superoxide dismutase). Additionally, CB enhanced the
      bacterial metabolism, especially that of carbohydrates, polymers, amino acids,
      carboxylic acids, and amines. These results revealed that dietary CB had a
      beneficial effect on the intestine health of L. vannamei by modulating the
      composition of the intestine microbiome, enhancing the microbial metabolism
      activity, and promoting the digestion and immunity of the host. The optimal
      dietary supplementation dosage was found to be 5.0 * 109 CFU kg-1 in the diet.

PMID- 30283420
TI  - Cucumber (Cucumis sativus L.) Seedling Rhizosphere Trichoderma and Fusarium spp.
      Communities Altered by Vanillic Acid.
AB  - Root exudates mediate soil microbiome composition and diversity, which might
      further influence plant development and health. Vanillic acid from root exudates
      is usually referred as autotoxin of cucumber, however, how vanillic acid affect
      soil microbial community diversities and abundances remains unclear. In this
      study, vanillic acid (VA; 0.02, 0.05, 0.1, and 0.2 MUmol g-1 soil) was applied to
      soil every other day for a total of five applications. We used Illumina MiSeq
      sequencing, quantitative PCR (qPCR) and PCR-denaturing gradient gel
      electrophoresis (PCR-DGGE) to test the effects of VA on the total fungi community
      composition as well as the Trichoderma and Fusarium spp. community abundances and
      structures in the cucumber rhizosphere. Illumina MiSeq sequencing showed that VA
      (0.05 MUmol g-1 soil) increased the relative abundance of the fungal phylum
      Basidiomycota while decreasing the relative abundance of Ascomycota (P < 0.05),
      and not altered the diversity of the soil fungal community. VA (0.05 MUmol g-1
      soil) also increased the relative abundances of the fungal genera with plant
      pathogens, such as Conocybe and Spizellomyces spp.(P < 0.05). A qPCR analysis
      showed that VA (0.05 to 0.2 MUmol g-1 soil) exerted promoting effects on
      Trichoderma spp. community abundance and stimulated Fusarium spp. abundance at
      low concentrations (0.02 to 0.05 MUmol g-1 soil) but inhibited it at high
      concentrations (0.1 to 0.2 MUmol g-1 soil). The PCR-DGGE analysis showed that all
      concentrations of VA altered the community structures of Trichoderma spp. and
      that the application of VA (0.02 and 0.05 MUmol g-1 soil) changed the band number
      and the Shannon-Wiener index of the Fusarium spp. community. This study
      demonstrated that VA changed the total fungal community in the cucumber seedling
      rhizosphere and that the Trichoderma and Fusarium spp. communities showed
      different responses to VA.

PMID- 30283421
TI  - Microbial Community Composition in Take-All Suppressive Soils.
AB  - Gaeumannomyces graminis var. tritici (Ggt) is the main soilborne factor that
      affects wheat production around the world. Recently we reported the occurrence of
      six suppressive soils in monoculture areas from indigenous "Mapuche" communities,
      and evidenced that the suppression relied on the biotic component of those soils.
      Here, we compare the rhizosphere and endosphere microbial community structure
      (total bacteria, actinomycetes, total fungi, and ascomycetes) of wheat plants
      grown in suppressive and conducive soils. Our results suggested that Ggt
      suppression could be mediated mostly by bacterial endophytes, rather than
      rhizosphere microorganisms, since the community structure was similar in all
      suppressive soils as compared with conducive. Interestingly, we found that
      despite the lower incidence of take-all disease in suppressive soils, the Ggt
      concentration in roots was not significantly reduced in all suppressive soils
      compared to those growing in conducive soil. Therefore, the disease suppression
      is not always related to a reduction of the pathogen biomass. Furthermore, we
      isolated endophytic bacteria from wheat roots growing in suppressive soils. Among
      them we identified Serratia spp. and Enterobacter spp. able to inhibit Ggt growth
      in vitro. Since the disease, but not always pathogen amount, was reduced in the
      suppressive soils, we propose that take all disease suppressiveness is not only
      related to direct antagonism to the pathogen.

PMID- 30283422
TI  - Chinese Black Truffle (Tuber indicum) Alters the Ectomycorrhizosphere and
      Endoectomycosphere Microbiome and Metabolic Profiles of the Host Tree Quercus
      aliena.
AB  - Truffles are one group of the most famous ectomycorrhizal fungi in the world.
      There is little information on the ecological mechanisms of truffle
      ectomycorrhizal synthesis in vitro. In this study, we investigated the ecological
      effects of Tuber indicum - Quercus aliena ectomycorrhizal synthesis on microbial
      communities in the host plant roots and the surrounding soil using high
      throughput sequencing and on the metabolic profiles of host plant roots using
      metabolomics approaches. We observed an increase in the diversity and richness of
      prokaryotic communities and a decrease in richness of fungal communities in the
      presence of T. indicum. The microbial community structures in the host roots and
      the surrounding soil were altered by ectomycorrhizal synthesis in the greenhouse.
      Bacterial genera Pedomicrobium, Variibacter, and Woodsholea and fungal genera
      Aspergillus, Phaeoacremonium, and Pochonia were significantly more abundant in
      ectomycorhizae and the ectomycorrhizosphere soil compared with the corresponding
      T. indicum-free controls (P < 0.05). Truffle-colonization reduced the abundance
      of some fungal genera surrounding the host tree, such as Acremonium, Aspergillus,
      and Penicillium. Putative prokaryotic metabolic functions and fungal functional
      groups (guilds) were also differentiated by ectomycorrhizal synthesis. The
      ectomycorrhizal synthesis had great impact on the measured soil physicochemical
      properties. Metabolic profiling analysis uncovered 55 named differentially
      abundant metabolites between the ectomycorhizae and the control roots, including
      44 upregulated and 11 downregulated metabolites. Organic acids and carbohydrates
      were two major upregulated metabolites in ectomycorhizae, which were found formed
      dense interactions with other metabolites, suggesting their crucial roles in
      sustaining the metabolic functions in the truffle ectomycorrhization system. This
      study revealed the effects of truffle-colonization on the metabolites of
      ectomycorrhiza and illustrates an interactive network between truffles, the host
      plant, soil and associated microbial communities, shedding light on understanding
      the ecological effects of truffles.

PMID- 30283423
TI  - A New Freshwater Cyanosiphovirus Harboring Integrase.
AB  - Pelagic cyanobacteria are key players in the functioning of aquatic ecosystems,
      and their viruses (cyanophages) potentially affect the abundance and composition
      of cyanobacterial communities. Yet, there are few well-described freshwater
      cyanophages relative to their marine counterparts, and in general, few
      cyanosiphoviruses (family Siphoviridae) have been characterized, limiting our
      understanding of the biology and the ecology of this prominent group of viruses.
      Here, we characterize S-LBS1, a freshwater siphovirus lytic to a phycoerythrin
      rich Synechococcus isolate (Strain TCC793). S-LBS1 has a narrow host range, a
      burst size of ~400 and a relatively long infecting step before cell lysis occurs.
      It has a dsDNA 34,641 bp genome with putative genes for structure, DNA packing,
      lysis, replication, host interactions, DNA repair and metabolism. S-LBS1 is
      similar in genome size, genome architecture, and gene content, to previously
      described marine siphoviruses also infecting PE-rich Synechococcus, e.g., S-CBS1
      and S-CBS3. However, unlike other Synechococcus phages, S-LBS1 encodes an
      integrase, suggesting its ability to establish lysogenic relationships with its
      host. Sequence recruitment from viral metagenomic data showed that S-LBS1-like
      viruses are diversely present in a wide range of aquatic environments,
      emphasizing their potential importance in controlling and structuring
      Synechococcus populations. A comparative analysis with 16 available sequenced
      cyanosiphoviruses reveals the absence of core genes within the genomes,
      suggesting high degree of genetic variability in siphoviruses infecting
      cyanobacteria. It is likely that cyanosiphoviruses have evolved as distinct
      evolutionary lineages and that adaptive co-evolution occurred between these
      viruses and their hosts (i.e., Synechococcus, Prochlorococcus, Nodularia, and
      Acaryochloris), constituting an important driving force for such phage
      diversification.

PMID- 30283424
TI  - Impact of Distribution and Network Flushing on the Drinking Water Microbiome.
AB  - We sampled the tap water of seven unique, full-scale drinking water distribution
      systems at different locations as well as the corresponding treatment plant
      effluents to evaluate the impact of distribution and the potential presence of a
      core drinking water microbiome. The water was also sampled during network
      flushing to examine its effect on the microbial ecology. While a core microbiome
      dominated by Gammaproteobacteria was found using 16S rRNA gene pyrosequencing, an
      increase in biomass was detected in the networks, especially during flushing.
      Water age did not significantly impact the microbiology. Irrespective of
      differences in treatment plants, tap water bacterial communities in the distinct
      networks converged and highly resembled the flushed water communities. Piping
      biofilm and sediment communities therefore largely determine the final tap water
      microbial quality, attenuating the impact of water source and treatment strategy
      and highlighting the fundamental role of local physicochemical conditions and
      microbial processes within infrastructure micro-niches.

PMID- 30283425
TI  - Characterizing the Human Mycobiota: A Comparison of Small Subunit rRNA, ITS1,
      ITS2, and Large Subunit rRNA Genomic Targets.
AB  - Interest in the human microbiome has increased dramatically in the last decade.
      However, much of this research has focused on bacteria, while the composition and
      roles of their fungal counterparts remain less understood. Furthermore, a variety
      of methodological approaches have been applied, and the comparability between
      studies is unclear. This study compared four primer pairs targeting the small
      subunit (SSU) rRNA (18S), ITS1, ITS2, and large subunit (LSU) rRNA (26S) genomic
      regions for their ability to accurately characterize fungal communities typical
      of the human mycobiota. All four target regions of 21 individual fungal mock
      community taxa were capable of being amplified adequately and sequenced. Mixed
      mock community analyses revealed marked variability in the ability of each primer
      pair to accurately characterize a complex community. ITS target regions
      outperformed LSU and SSU. Of the ITS regions, ITS1 failed to generate sequences
      for Yarrowia lipolytica and all three Malassezia species when in a mixed
      community. These findings were further supported in studies of human sinonasal
      and mouse fecal samples. Based on these analyses, previous studies using ITS1,
      SSU, or LSU markers may omit key taxa that are identified by the ITS2 marker. Of
      methods commonly used in human mycobiota studies to date, we recommend selection
      of the ITS2 marker. Further investigation of more recently developed fungal
      primer options will be essential to ultimately determine the optimal
      methodological approach by which future human mycobiota studies ought to be
      standardized.

PMID- 30283427
TI  - Microbial Inoculants for Improving Crop Quality and Human Health in Africa.
AB  - Current agricultural practices depend heavily on chemical inputs (such as
      fertilizers, pesticides, herbicides, etc.) which, all things being equal cause a
      deleterious effect on the nutritional value of farm product and health of farm
      workers and consumers. Excessive and indiscriminate use of these chemicals have
      resulted in food contamination, weed and disease resistance and negative
      environmental outcomes which together have a significant impact on human health.
      Application of these chemical inputs promotes the accumulation of toxic compounds
      in soils. Chemical compounds are absorbed by most crops from soil. Several
      synthetic fertilizers contain acid radicals, such as hydrochloride and sulfuric
      radicals, and hence increase the soil acidity and adversely affect soil and plant
      health. Highly recalcitrant compounds can also be absorbed by some plants.
      Continuous consumption of such crops can lead to systematic disorders in humans.
      Quite a number of pesticides and herbicides have carcinogenicity potential. The
      increasing awareness of health challenges as a result of consumption of poor
      quality crops has led to a quest for new and improved technologies of improving
      both the quantity and quality of crop without jeopardizing human health. A
      reliable alternative to the use of chemical inputs is microbial inoculants that
      can act as biofertilizers, bioherbicide, biopesticides, and biocontrol agents.
      Microorganisms are able to carry out the plant growth promotion, pest and disease
      and weed control. Microbial inoculants are beneficiary microorganisms applied to
      either the soil or the plant in order to improve productivity and crop health.
      Microbial inoculants are natural-based products being widely used to control
      pests and improve the quality of the soil and crop, and hence human health.
      Microbial inoculants involve a blend of microorganisms that work with the soil
      and the soil life to improve soil fertility and health and by extension improve
      human health. Microbial inoculants have the ability to minimize the negative
      impact of chemical input and consequently increase the quantity and quality of
      farm produce. Microbial inoculants are environmental-friendly and deliver plant
      nutrients to plants in a more sustainable manner. Microbial inoculants can help
      reduce chemical fertilizer application. Microbial inoculants could include
      bacteria, fungi and algae. This research summarizes the impact of agricultural
      chemical inputs on human health. The contribution of microbial inoculants in
      sustainable maintenance of human health will be expatiated. Advances in microbial
      inoculants and technology and strategies to explore this natural, user friendly
      biological resource for sustainable maintenance of plant health will be
      discussed.

PMID- 30283426
TI  - A Class 1 Histone Deacetylase as Major Regulator of Secondary Metabolite
      Production in Aspergillus nidulans.
AB  - An outstanding feature of filamentous fungi is their ability to produce a wide
      variety of small bioactive molecules that contribute to their survival, fitness,
      and pathogenicity. The vast collection of these so-called secondary metabolites
      (SMs) includes molecules that play a role in virulence, protect fungi from
      environmental damage, act as toxins or antibiotics that harm host tissues, or
      hinder microbial competitors for food sources. Many of these compounds are used
      in medical treatment; however, biosynthetic genes for the production of these
      natural products are arranged in compact clusters that are commonly silent under
      growth conditions routinely used in laboratories. Consequently, a wide arsenal of
      yet unknown fungal metabolites is waiting to be discovered. Here, we describe the
      effects of deletion of hosA, one of four classical histone deacetylase (HDAC)
      genes in Aspergillus nidulans; we show that HosA acts as a major regulator of SMs
      in Aspergillus with converse regulatory effects depending on the metabolite gene
      cluster examined. Co-inhibition of all classical enzymes by the pan HDAC
      inhibitor trichostatin A and the analysis of HDAC double mutants indicate that
      HosA is able to override known regulatory effects of other HDACs such as the
      class 2 type enzyme HdaA. Chromatin immunoprecipitation analysis revealed a
      direct correlation between hosA deletion, the acetylation status of H4 and the
      regulation of SM cluster genes, whereas H3 hyper-acetylation could not be
      detected in all the upregulated SM clusters examined. Our data suggest that HosA
      has inductive effects on SM production in addition to its classical role as a
      repressor via deacetylation of histones. Moreover, a genome wide transcriptome
      analysis revealed that in addition to SMs, expression of several other important
      protein categories such as enzymes of the carbohydrate metabolism or proteins
      involved in disease, virulence, and defense are significantly affected by the
      deletion of HosA.

PMID- 30283428
TI  - In vitro Probiotic Potential and Anti-cancer Activity of Newly Isolated Folate
      Producing Streptococcus thermophilus Strains.
AB  - Most probiotic strains commercially available today are lactic acid bacteria.
      Within this functional group, Streptococcus thermophilus is a thermophilic
      species widely used as starter culture for a huge number of dairy products.
      Besides being rapid acidifiers, many S. thermophilus strains are able to produce
      and release folate during growth but, unfortunately, they are seriously impaired
      during passage through the human gastrointestinal tract. In this work, we studied
      eight S. thermophilus strains isolated from dairy environments in Italy, which
      already had shown good technological properties, to evaluate their possible
      probiotic potential and cytotoxicity against cancer cells in vitro. All strains
      were also evaluated for some health-related properties such as susceptibility to
      most common antibiotics, hemolytic activity, resistance to simulated
      gastrointestinal conditions, bile salts hydrolytic activity, production of
      folate, adhesion to HT-29 human colorectal adenocarcinoma cells and cytotoxic
      activity against cancer cells and production of biogenic amines. Results revealed
      that two fast acidifying S. thermophilus strains were found to possess in vitro
      probiotic properties along with anticancer activity and production of folate.
      These properties resulted similar and, in some cases, superior to those of
      Lactobacillus rhamnosus GG, a well-known commercial probiotic strain. These
      findings encourage further in vivo studies to evaluate the actual health benefits
      of these strains on the human host.

PMID- 30283429
TI  - Occurrence, Antibiotic Resistance, and Population Diversity of Listeria
      monocytogenes Isolated From Fresh Aquatic Products in China.
AB  - Listeria monocytogenes is an important Gram-positive foodborne pathogen. However,
      limited information is available on the comprehensive investigation and potential
      risk of L. monocytogenes in fresh aquatic products, which are popular to
      consumers in China. This study aimed to determine the occurrence, virulence
      profiles, and population diversity of L. monocytogenes isolated from aquatic
      products in China. In total, 846 aquatic product samples were collected between
      July 2011 and April 2016 from 43 cities in China. Approximately 7.92% (67/846)
      aquatic product samples were positive for L. monocytogenes, 86.57% positive
      samples ranged from 0.3 to 10 MPN/g, whereas 5.97% showed over 110 MPN/g by the
      Most Probable Number method, which included two samples of products intended to
      be eaten raw. Serogroups I.1 (serotype 1/2a), I.2 (serotype 1/2b), and III
      (serotype 4c) were the predominant serogroups isolated, whereas serogroup II.1
      (serotype 4b) was detected at much lower frequencies. Examination of
      antibacterial resistance showed that nine antibacterial resistance profiles were
      exhibited in 72 isolates, a high level susceptibility of 16 tested antibiotics
      against L. monocytogenes were observed, indicating these common antibacterial
      agents are still effective for treating L. monocytogenes infection. Multilocus
      sequence typing revealed that ST299, ST87, and ST8 are predominant in aquatic
      products, indicating that the rare ST299 (serotype 4c) may have a special
      ecological niche in aquatic products and associated environments. Except llsX and
      ptsA, the 72 isolates harbor nine virulence genes (prfA, actA, hly, plcA, plcB,
      iap, mpl, inlA, and inlB), premature stop codons (PMSCs) in inlA were found in
      four isolates, three of which belonged to ST9. A novel PMSC was found in 2929-1LM
      with a nonsense mutation at position 1605 (TGG->TGA). All ST87 isolates harbored
      the ptsA gene, whereas 8 isolates (11.11%) carried the llsX gene, and mainly
      belonged to ST1, ST3, ST308, ST323, ST330, and ST619. Taken together, these
      results first reported potential virulent L. monocytogenes isolates (ST8 and
      ST87) were predominant in aquatic products which may have implications for public
      health in China. It is thus necessary to perform continuous surveillance for L.
      monocytogenes in aquatic products in China.

PMID- 30283430
TI  - Detection of Viral Pathogens With Multiplex Nanopore MinION Sequencing: Be
      Careful With Cross-Talk.
AB  - Metagenomic sequencing with the Oxford Nanopore MinION sequencer offers potential
      for point-of-care testing of infectious diseases in clinical settings. To improve
      cost-effectiveness, multiplexing of several, barcoded samples upon a single flow
      cell will be required during sequencing. We generated a unique sequencing dataset
      to assess the extent and source of cross barcode contamination caused by
      multiplex MinION sequencing. Sequencing libraries for three different viruses,
      including influenza A, dengue, and chikungunya, were prepared separately and
      sequenced on individual flow cells. We also pooled the respective libraries and
      performed multiplex sequencing. We identified 0.056% of total reads in the
      multiplex sequencing data that were assigned to incorrect barcodes. Chimeric
      reads were the predominant source of this error. Our findings highlight the need
      for careful filtering of multiplex sequencing data before downstream analysis,
      and the trade-off between sensitivity and specificity that applies to the barcode
      demultiplexing methods.

PMID- 30283431
TI  - Species Pervasiveness Within the Group of Coagulase-Negative Staphylococci
      Associated With Meat Fermentation Is Modulated by pH.
AB  - During spontaneous meat fermentations, Staphylococcus equorum, Staphylococcus
      saprophyticus, and Staphylococcus xylosus are generally the most prevailing
      species within the communities of coagulase-negative staphylococci (CNS). There
      is an interest to introduce CNS isolates from artisan-style spontaneous meat
      fermentations as starter cultures in more industrialized processes, as to confer
      additional quality benefits. However, staphylococcal competitiveness within the
      meat matrix is affected by the processing conditions, which vary considerably
      among product types. A major factor of variability relates to the intensity of
      acidification, driven by the concentration of added carbohydrates. The effect of
      pH on CNS prevalence was studied in both a mince-based meat fermentation model
      and in fermented sausages produced on pilot scale. Roughly, from all experiments
      combined, it appeared that a pH of 5.3 corresponded with a breakpoint for CNS
      selection. Above this value, a general prevalence by S. xylosus was found, even
      overruling the addition of starter cultures consisting of S. equorum and S.
      saprophyticus strains. At pH values below 5.3, S. xylosus was also accompanied by
      S. equorum (following a mild pH drop) and S. saprophyticus (following a stronger
      pH drop). Still, addition of starter cultures affected the volatile profile
      compared to the control batch, even if those starter cultures were not able to
      dominate during the ripening process. This study nonetheless provides a warning
      for an overly confident use of specific CNS species as starter cultures,
      especially when in a given processing context the prevailing conditions do not
      allow superior growth compared to the CNS from the background microbiota.

PMID- 30283432
TI  - Alterations of the Gut Microbiome Associated With the Treatment of Hyperuricaemia
      in Male Rats.
AB  - Hyperuricaemia is an important risk factor for many diseases including gout,
      hypertension, and type II diabetes. The gut microbiota is associated with
      hyperuricaemia and has also been demonstrated to play significant roles in the
      effects of drug therapy. This study used Illumina MiSeq sequencing to explore
      alterations of the gut microbiome associated with allopurinol and benzbromarone
      treatment in the male rat with hyperuricaemia. After drug treatment, both
      allopurinol and benzbromarone caused an increase of the genera Bifidobacterium
      and Collinsella and a decrease of the genera Adlercreutzia and Anaerostipes. In
      addition, allopurinol and benzbromarone caused respective unique changes in
      genera. The genera Bilophila, Morganella, and Desulfovibrio specifically
      decreased due to allopurinol treatment. Decreased Butyricimonas and Ruminococcus
      and increased Proteus were caused by benzbromarone treatment. The PICRUST
      analysis indicated that allopurinol renovated the disorder of nucleotide
      metabolism and benzbromarone renovated the disorder of lipid metabolism in the
      gut microbiota of male rats with hyperuricaemia. These findings demonstrated that
      the gut microbiota may be altered by the treatment of hyperuricaemia with
      allopurinol and benzbromarone in male rats. Such alterations of the gut
      microbiota could be considered as indicators of the effectiveness of drug
      therapy.

PMID- 30283433
TI  - Bicarbonate Inhibits Bacterial Growth and Biofilm Formation of Prevalent Cystic
      Fibrosis Pathogens.
AB  - We investigated the effects of bicarbonate on the growth of several different
      bacteria as well as its effects on biofilm formation and intracellular cAMP
      concentration in Pseudomonas aeruginosa. Biofilm formation was examined in 96
      well plates, with or without bicarbonate. The cAMP production of bacteria was
      measured by a commercial assay kit. We found that NaHCO3 (100 mmol l-1)
      significantly inhibited, whereas NaCl (100 mmol l-1) did not influence the growth
      of planktonic bacteria. MIC and MBC measurements indicated that the effect of
      HCO3- is bacteriostatic rather than bactericidal. Moreover, NaHCO3 prevented
      biofilm formation as a function of concentration. Bicarbonate and alkalinization
      of external pH induced a significant increase in intracellular cAMP levels. In
      conclusion, HCO3- impedes the planktonic growth of different bacteria and impedes
      biofilm formation by P. aeruginosa that is associated with increased
      intracellular cAMP production. These findings suggest that aerosol inhalation
      therapy with HCO3- solutions may help improve respiratory hygiene in patients
      with cystic fibrosis and possibly other chronically infected lung diseases.

PMID- 30283434
TI  - New Vaccine Technologies to Combat Outbreak Situations.
AB  - Ever since the development of the first vaccine more than 200 years ago,
      vaccinations have greatly decreased the burden of infectious diseases worldwide,
      famously leading to the eradication of small pox and allowing the restriction of
      diseases such as polio, tetanus, diphtheria, and measles. A multitude of research
      efforts focuses on the improvement of established and the discovery of new
      vaccines such as the HPV (human papilloma virus) vaccine in 2006. However,
      radical changes in the density, age distribution and traveling habits of the
      population worldwide as well as the changing climate favor the emergence of old
      and new pathogens that bear the risk of becoming pandemic threats. In recent
      years, the rapid spread of severe infections such as HIV, SARS, Ebola, and Zika
      have highlighted the dire need for global preparedness for pandemics, which
      necessitates the extremely rapid development and comprehensive distribution of
      vaccines against potentially previously unknown pathogens. What is more, the
      emergence of antibiotic resistant bacteria calls for new approaches to prevent
      infections. Given these changes, established methods for the identification of
      new vaccine candidates are no longer sufficient to ensure global protection.
      Hence, new vaccine technologies able to achieve rapid development as well as
      large scale production are of pivotal importance. This review will discuss viral
      vector and nucleic acid-based vaccines (DNA and mRNA vaccines) as new approaches
      that might be able to tackle these challenges to global health.

PMID- 30283436
TI  - Essential Domain-Dependent Roles Within Soluble IgG for in vivo Superantigen
      Properties of Staphylococcal Protein A: Resolving the B-Cell Superantigen
      Paradox.
AB  - Staphylococcus aureus is a common commensal and frequent opportunistic pathogen
      that causes invasive infections that often recur. Co-evolution with the host has
      led to the development of toxins that affect diverse immune cell types. Recent
      reports have highlighted the contributions of staphylococcal protein A (SpA).
      This small oligomeric secreted protein contains 4-5 homologous domains with two
      distinct immunoglobulin-binding sites; one for IgG Fc domains, while a separate
      site binds an evolutionarily conserved surface on Fab encoded by VHIII clan
      related genes. The Fab-binding site has been implicated in in vivo supraclonal
      VHIII-BCR targeted B-cell depletion by an activation induced death pathway. Yet
      the concept of a superantigen for B lymphocytes poses a seeming paradox. Unlike
      TCR that are expressed only in a membrane-associated form, BCR are expressed in
      both a membrane BCR form and in secreted Ig forms, which permeate virtually every
      part of the body at high levels. We therefore asked, why circulating
      immunoglobulin do not block the superantigen properties of SpA? Herein, we show
      that soluble IgG molecules are not in vivo inhibitors of these B-cell
      superantigen effects but are instead essential for potentiating these properties.
      We also show that the Fc subclass of circulating IgG is an indirect critical
      determinant of the B-cell superantigen effect. In contrast, host FcgammaR and
      complement are not required for SpA mediated in vivo B-cell depletion.
      Unexpectedly, after VHIII-IgG2a pretreatment SpA challenge resulted in fatal
      anaphylactic reactions, which we speculate may have involved FcgammaR
      interactions with mast cells and basophils. Cumulatively, our findings illuminate
      a cunning and potent molecular strategy by which a bacterial toxin effectively
      confounds the contributions of host B-lymphocytes to immune defenses.

PMID- 30283437
TI  - Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages
      Through Src-STAT3 Signaling Pathway.
AB  - The aryl hydrocarbon receptor (AhR) is an important immune regulator with a role
      in inflammatory response. However, the role of AhR in IL-10 production by
      inflammatory macrophages is currently unknown. In this study, we investigated LPS
      induced IL-10 expression in macrophages from AhR-KO mice and AhR-overexpressing
      RAW264.7 cells. AhR was highly expressed after LPS stimulation through NF-kappaB
      pathway. Loss of AhR resulted in reduced IL-10 expression in LPS-induced
      macrophages. Moreover, the IL-10 expression was elevated in LPS-induced AhR
      overexpressing RAW264.7 cells. Maximal IL-10 expression was dependent on an AhR
      non-genomic pathway closely related to Src and STAT3. Furthermore, AhR-associated
      Src activity was responsible for tyrosine phosphorylation of STAT3 and IL-10
      expression by inflammatory macrophages. Adoptive transfer of AhR-expressing
      macrophages protected mice against LPS-induced peritonitis associated with high
      IL-10 production. In conclusion, we identified the AhR-Src-STAT3-IL-10 signaling
      pathway as a critical pathway in the immune regulation of inflammatory
      macrophages, It suggests that AhR may be a potential therapeutic target in immune
      response.

PMID- 30283438
TI  - Inflammatory Endotypes and Microbial Associations in Chronic Rhinosinusitis.
AB  - A complex mix of inflammatory and microbial associations underscores the chronic
      inflammatory condition chronic rhinosinusitis (CRS), and the etiology remains
      poorly understood. Recent work has begun to delineate between variants
      (endotypes) of CRS on the basis of inflammatory biomarkers. This study aimed to
      assess inflammatory patterns in CRS phenotypes, identify putative endotypes of
      CRS, and to assess inflammatory associations with the sinonasal microbiota. Ten
      cytokines and six inflammatory cell types were assessed in mucosal biopsies from
      93 CRS subjects and 17 controls via cytometric bead array and immunohistochemical
      techniques. Putative endotypes were identified via cluster analysis of subjects
      on the basis of inflammatory markers and comorbidities including polyposis,
      asthma, and aspirin sensitivity. Finally, previously published bacterial data for
      this cohort were reanalyzed to evaluate associations with inflammatory markers
      and CRS subtypes. Inflammatory patterns were highly variable within standard CRS
      phenotypes. Cluster analysis identified eight subject clusters, with strong
      delineation on the basis of polyposis and asthma, but also subtle distinctions in
      inflammatory markers. An association was also identified between depletion of
      several "health-associated" bacterial taxa, reduced bacterial diversity and
      increased overall bacterial load, with markers of inflammation and clinical
      severity. This study contributes to ongoing efforts to define distinct endotypes
      of CRS on the basis of underlying inflammatory processes, and also offers
      compelling evidence of a link between bacterial community dysbiosis and
      inflammation in CRS. Further resolving the heterogeneity of CRS is vital to
      inform clinical management and personalized treatment approaches.

PMID- 30283435
TI  - A Potential Link Between Oxidative Stress and Endothelial-to-Mesenchymal
      Transition in Systemic Sclerosis.
AB  - Systemic sclerosis (SSc), an autoimmune disease that is associated with a number
      of genetic and environmental risk factors, is characterized by progressive
      fibrosis and microvasculature damage in the skin, lungs, heart, digestive system,
      kidneys, muscles, joints, and nervous system. These abnormalities are associated
      with altered secretion of growth factor and profibrotic cytokines, such as
      transforming growth factor-beta (TGF-beta), interleukin-4 (IL-4), platelet
      derived growth factor (PDGF), and connective-tissue growth factor (CTGF). Among
      the cellular responses to this proinflammatory environment, the endothelial cells
      phenotypic conversion into activated myofibroblasts, a process known as
      endothelial to mesenchymal transition (EndMT), has been postulated. Reactive
      oxygen species (ROS) might play a key role in SSs-associated fibrosis and
      vascular damage by mediating and/or activating TGF-beta-induced EndMT, a
      phenomenon that has been observed in other disease models. In this review, we
      identified and critically appraised published studies investigating associations
      ROS and EndMT and the presence of EndMT in SSc, highlighting a potential link
      between oxidative stress and EndMT in this condition.

PMID- 30283439
TI  - Toxoplasma Effector TgIST Targets Host IDO1 to Antagonize the IFN-gamma-Induced
      Anti-parasitic Response in Human Cells.
AB  - Toxoplasma gondii is an important human and animal pathogen that causes life
      threatening toxoplasmosis. Interferon-gamma (IFN-gamma) is critical for anti-T.
      gondii cell-autonomous immunity in both humans and mice. To proliferate
      efficiently within the hosts, virulent strains of T. gondii can suppress IFN
      gamma-dependent immunity. During parasite infection, it is well-characterized
      that various virulence effectors are secreted to transcriptionally or post
      translationally target IFN-gamma-inducible GTPases, which are essential for anti
      parasite responses in mice. However, the role of IFN-gamma-inducible GTPases in
      anti-T. gondii responses in human cells is controversial since they are non
      functional or absent in humans. Instead, IFN-gamma-induced tryptophan degradation
      by indole-2,3-dioxygenase (IDO) is important for the anti-T. gondii human
      response. To date, the T. gondii virulent mechanism targeting IDO in human cells
      remains elusive. Here we show that although humans possess two IDO isozymes, IDO1
      and IDO2, human cells of various origins require IDO1 but not IDO2 for IFN-gamma
      induced cell-autonomous immunity to T. gondii. T. gondii secretes an effector
      TgIST to inhibit IDO1 mRNA expression. Taken together, the data suggests that T.
      gondii possesses virulence programs operated by TgIST to antagonize IFN-gamma
      induced IDO1-mediated anti-parasite cell-autonomous immunity in human cells.

PMID- 30283441
TI  - Decidual-Placental Immune Landscape During Syngeneic Murine Pregnancy.
AB  - Adaptive immune system, principally governed by the T cells-dendritic cells (DCs)
      nexus, is an essential mediator of gestational fetal tolerance and protection
      against infection. However, the exact composition and dynamics of DCs and T cell
      subsets in gestational tissues are not well understood. These are controlled in
      human physiology by a complex interplay of alloantigen distribution and
      presentation, cellular/humoral active and passive tolerance,
      hormones/chemokines/angiogenic factors and their gradients, systemic and local
      microbial communities. Reductive discrimination of these factors in physiology
      and pathology of model systems and humans requires simplification of the model
      and increased resolution of interrogative technologies. As a baseline, we have
      studied the gestational tissue dynamics in the syngeneic C57BL/6 mice, as the
      simplest immunological environment, and focused on validating the approach to
      increased data density and computational analysis pipeline afforded by highly
      polychromatic flow cytometry and machine learning interpretation. We mapped DC
      and T cell subsets, and comprehensively examined their maternal (decidual)-fetal
      (placental) interface dynamics. Both frequency and composition of decidual DCs
      changed across gestation, with a dramatic increase in myeloid DCs in early
      pregnancy, and exclusion of plasmacytoid DCs. CD4+ T cells, in contrast, were
      lower at all gestational ages and an unusual CD4-CD8-TCRalphabeta+group was
      prominent at mid-pregnancy. Dimensionality reduction with machine learning-aided
      clustering revealed that CD4-CD8- T cells were phenotypically different from CD4+
      and CD8+ T cells. Additionally, divergence between maternal decidual and fetal
      placental compartment was prominent, with absence of DCs from the placenta, but
      not decidua or embryo. These results provide a novel framework and a syngeneic
      baseline on which the specific role of alloantigen/tolerance, polymicrobial
      environment, and models of pregnancy pathology can be precisely modeled and
      analyzed.

PMID- 30283440
TI  - The CBM-opathies-A Rapidly Expanding Spectrum of Human Inborn Errors of Immunity
      Caused by Mutations in the CARD11-BCL10-MALT1 Complex.
AB  - The caspase recruitment domain family member 11 (CARD11 or CARMA1)-B cell
      CLL/lymphoma 10 (BCL10)-MALT1 paracaspase (MALT1) [CBM] signalosome complex
      serves as a molecular bridge between cell surface antigen receptor signaling and
      the activation of the NF-kappaB, JNK, and mTORC1 signaling axes. This positions
      the CBM complex as a critical regulator of lymphocyte activation, proliferation,
      survival, and metabolism. Inborn errors in each of the CBM components have now
      been linked to a diverse group of human primary immunodeficiency diseases termed
      "CBM-opathies." Clinical manifestations range from severe combined
      immunodeficiency to selective B cell lymphocytosis, atopic disease, and specific
      humoral defects. This surprisingly broad spectrum of phenotypes underscores the
      importance of "tuning" CBM signaling to preserve immune homeostasis. Here, we
      review the distinct clinical and immunological phenotypes associated with human
      CBM complex mutations and introduce new avenues for targeted therapeutic
      intervention.

PMID- 30283442
TI  - CD8+ Resident Memory T Cells and Viral Infection.
AB  - Tissue-resident memory T (Trm) cells are a subset of recently identified memory T
      cells that mainly reside and serve as sentinels in non-lymphoid peripheral
      tissues. Unlike the well-characterized circulating central memory T (Tcm) cells
      and effector memory T (Tem) cells, Trm cells persist in the tissues, do not
      recirculate into blood, and offer immediate protection against pathogens upon
      reinfection. In this review, we focus on CD8+ Trm cells and briefly introduce
      their characteristics, development, maintenance, and function during viral
      infection. We also discuss some unresolved problems, such as how CD8+ Trm cells
      adapt to the local tissue microenvironment, how Trm cells interact with other
      immune cells during their development and maintenance, and the mechanisms by
      which CD8+ Trm cells confer immune protection. We believe that a better
      understanding of these problems is of great clinical and therapeutic value and
      may contribute to more effective vaccination and treatments against viral
      infection.

PMID- 30283443
TI  - Vibrio vulnificus RtxA Is a Major Factor Driving Inflammatory T Helper Type 17
      Cell Responses in vitro and in vivo.
AB  - T helper type 17 (Th17) cells are a subset of pro-inflammatory T helper cells
      that mediate host defense and pathological inflammation. We have previously
      reported that host dendritic cells (DCs) infected with Vibrio vulnificus induce
      Th17 responses through the production of several pro-inflammatory cytokines,
      including interleukin (IL)-1beta and IL-6. V. vulnificus produces RTX toxin
      (RtxA), an important virulence factor that determines successful pathophysiology.
      In this study, we investigated the involvement of RtxA from V. vulnificus in Th17
      cell induction through the activation and maturation of DCs. The increased
      expression of the DC surface marker CD40 caused by V. vulnificus wild-type
      infection was reduced by rtxA gene mutation in V. vulnificus. The mRNA and
      protein levels of Th17 polarization-related cytokines also decreased in V.
      vulnificus rtxA mutant-infected DCs. In addition, the co-culture of Th cells and
      DCs infected with rtxA mutant V. vulnificus resulted in reduction in DC-mediated
      Th17 responses. Th17 cell responses in the small intestinal lamina propria
      decreased in mice inoculated with V. vulnificus rtxA mutant as compared to those
      inoculated with the wild-type strain. These decreases in DC maturation, Th17
      polarizing cytokine secretion, and Th17 responses attributed to rtxA mutation
      were restored following infection with the rtxA revertant strain. Furthermore,
      the mutation in the hlyU gene encoding the activator of rtxA1 gene reproduced the
      results observed with rtxA mutation. Taken together, V. vulnificus, by means of
      RtxA, induces inflammatory Th17 responses, which may be associated with adaptive
      responses of the host against V. vulnificus infection.

PMID- 30283444
TI  - RNA Structure-A Neglected Puppet Master for the Evolution of Virus and Host
      Immunity.
AB  - The central dogma of molecular biology describes the flow of genetic information
      from DNA to protein via an RNA intermediate. For many years, RNA has been
      considered simply as a messenger relaying information between DNA and proteins.
      Recent advances in next generation sequencing technology, bioinformatics, and non
      coding RNA biology have highlighted the many important roles of RNA in virtually
      every biological process. Our understanding of RNA biology has been further
      enriched by a number of significant advances in probing RNA structures. It is now
      appreciated that many cellular and viral biological processes are highly
      dependent on specific RNA structures and/or sequences, and such reliance will
      undoubtedly impact on the evolution of both hosts and viruses. As a contribution
      to this special issue on host immunity and virus evolution, it is timely to
      consider how RNA sequences and structures could directly influence the co
      evolution between hosts and viruses. In this manuscript, we begin by stating some
      of the basic principles of RNA structures, followed by describing some of the
      critical RNA structures in both viruses and hosts. More importantly, we highlight
      a number of available new tools to predict and to evaluate novel RNA structures,
      pointing out some of the limitations readers should be aware of in their own
      analyses.

PMID- 30283445
TI  - Neutrophil Activation in Acute Hemorrhagic Fever With Renal Syndrome Is Mediated
      by Hantavirus-Infected Microvascular Endothelial Cells.
AB  - Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus
      cardiopulmonary syndrome (HCPS) in humans. Both diseases are considered to be
      immunologically mediated but the exact pathological mechanisms are still poorly
      understood. Neutrophils are considered the first line of defense against invading
      microbes but little is still known of their role in virus infections. We wanted
      to study the role of neutrophils in HFRS using blood and tissue samples obtained
      from Puumala hantavirus (PUUV)-infected patients. We found that neutrophil
      activation products myeloperoxidase and neutrophil elastase, together with
      interleukin-8 (the major neutrophil chemotactic factor in humans), are strongly
      elevated in blood of acute PUUV-HFRS and positively correlate with kidney
      dysfunction, the hallmark clinical finding of HFRS. These markers localized
      mainly in the tubulointerstitial space in the kidneys of PUUV-HFRS patients
      suggesting neutrophil activation to be a likely component of the general immune
      response toward hantaviruses. We also observed increased levels of circulating
      extracellular histones at the acute stage of the disease supporting previous
      findings of neutrophil extracellular trap formation in PUUV-HFRS.
      Mechanistically, we did not find evidence for direct PUUV-mediated activation of
      neutrophils but instead primary blood microvascular endothelial cells acquired a
      pro-inflammatory phenotype and promoted neutrophil degranulation in response to
      PUUV infection in vitro. These results suggest that neutrophils are activated by
      hantavirus-infected endothelial cells and may contribute to the kidney pathology
      which determines the severity of HFRS.

PMID- 30283446
TI  - Gene Expression Analysis Identifies Novel Targets for Cervical Cancer Therapy.
AB  - Although there has been significant progress in prevention and treatment of
      cervical cancer, this malignancy is still a leading cause of cancer death for
      women. Anti-angiogenesis and immunotherapy approaches have been providing
      survival benefits, however, response rates and durability of response need to be
      improved. There is a clear need for combination therapies that increase
      effectiveness of these agents and further improve patient outcome. Previous
      studies have largely focused on gene expression and molecular pathways in
      untreated cervix cancer. The goal of this study was to evaluate cancer-specific
      molecular pathways and their correlation with tumor immune profile in recurrent
      cervical cancer. Tumor and adjacent normal tissues were used to identify
      potential combination therapy targets. We found that DNA damage repair pathway
      genes were significantly overexpressed in the tumor. Based on our results and
      other recent investigations, we suggest that combination immune checkpoint and
      PARP inhibitor therapy is a high priority consideration for patients with
      recurrent, previously treated cervical cancer. We also show that multiple
      epithelial-mesenchymal transition-related genes, including MAP2K4, ID2, JAK1,
      FGF2, PIK3R1, AKT3, FGF13, and STAT3 may be potential targets. Interestingly,
      high-throughput analysis of Cancer Genome Atlas data identified distinct targets,
      including Fatty acid synthase FASN and Matrix Metallopeptidase 1 MMP1 as novel,
      promising combination therapy partners.

PMID- 30283448
TI  - The Pathogenesis of Tuberculosis: The Early Infiltrate of Post-primary (Adult
      Pulmonary) Tuberculosis: A Distinct Disease Entity.
AB  - It has long been recognized that tuberculosis (TB) induces both protective and
      tissue damaging immune responses. This paper reviews nearly two centuries of
      evidence that protection and tissue damage are mediated by separate disease
      entities in humans. Primary TB mediates protective immunity to disseminated
      infection while post-primary TB causes tissue damage that results in formation of
      cavities. Both are necessary for continued survival of Mycobacterium tuberculosis
      (MTB). Primary TB has been extensively studied in humans and animals. Post
      primary TB, in contrast, is seldom recognized or studied. It begins as an
      asymptomatic early infiltrate that may resolve or progress by bronchogenic spread
      to caseous pneumonia that either fragments to produce cavities or is retained to
      produce post-primary granulomas and fibrocaseous disease. Primary and post
      primary TB differ in typical age of onset, histopathology, organ distribution, x
      ray appearance, genetic predisposition, immune status of the host, clinical
      course and susceptibility to protection by BCG. MTB is a highly successful human
      parasite because it produces both primary and post-primary TB as distinct disease
      entities in humans. No animal reproduces this sequence of lesions. Recognition of
      these facts immediately suggests plausible solutions, animal models and testable
      hypotheses to otherwise inaccessible questions of the immunity and pathogenesis
      of TB.

PMID- 30283447
TI  - Mechanisms of Regulated and Dysregulated CARD11 Signaling in Adaptive Immunity
      and Disease.
AB  - CARD11 functions as a key signaling scaffold that controls antigen-induced
      lymphocyte activation during the adaptive immune response. Somatic mutations in
      CARD11 are frequently found in Non-Hodgkin lymphoma, and at least three classes
      of germline CARD11 mutations have been described as the basis for primary
      immunodeficiency. In this review, we summarize our current understanding of how
      CARD11 signals, how its activity is regulated, and how mutations bypass normal
      regulation to cause disease.

PMID- 30283450
TI  - Commentary: Integrins Modulate T Cell Receptor Signaling by Constraining Actin
      Flow at the Immunological Synapse.

PMID- 30283449
TI  - Glibenclamide Reduces Primary Human Monocyte Functions Against Tuberculosis
      Infection by Enhancing M2 Polarization.
AB  - Tuberculosis (TB) is a global public health problem, which is caused by
      Mycobacterium tuberculosis (Mtb). Type 2 diabetes mellitus (T2DM) is one of the
      leading predisposing factors for development of TB after HIV/AIDS. Glibenclamide
      is a widely used anti-diabetic drug in low and middle-income countries where the
      incidence of TB is very high. In a human macrophage cell line, glibenclamide, a
      K+ATP-channel blocker, promoted alternative activation of macrophages by
      enhancing expression of the M2 marker CD206 during M2 polarization. M2
      macrophages are considered poorly microbicidal and associated with TB
      susceptibility. Here, we investigated the effect of glibenclamide on M1 and M2
      phenotypes of primary human monocytes and further determined whether specific
      drug treatment for T2DM individuals influences the antibacterial function of
      monocytes in response to mycobacterial infection. We found that glibenclamide
      significantly reduced M1 (HLA-DR+ and CD86+) surface markers and TNF-alpha
      production on primary human monocytes against mycobacterial infection. In
      contrast, M2 (CD163+ and CD206+) surface markers and IL-10 production were
      enhanced by pretreatment with glibenclamide. Additionally, reduction of
      bactericidal activity also occurred when primary human monocytes from T2DM
      individuals who were being treated with glibenclamide were infected with Mtb in
      vitro, consistent with the cytokine responses. We conclude that glibenclamide
      reduces M1 and promotes M2 polarization leading to impaired bactericidal ability
      of primary human monocytes of T2DM individuals in response to Mtb and may lead to
      increased susceptibility of T2DM individuals to TB and other bacterial infectious
      diseases.

PMID- 30283451
TI  - Galleria mellonella: A Novel Invertebrate Model to Distinguish Intestinal
      Symbionts From Pathobionts.
AB  - Insects and mammals share evolutionary conserved innate immune responses to
      maintain intestinal homeostasis. We investigated whether the larvae of the
      greater wax moth Galleria mellonella may be used as an experimental organism to
      distinguish between symbiotic Bacteroides vulgatus and pathobiotic Escherichia
      coli, which are mammalian intestinal commensals. Oral application of the symbiont
      or pathobiont to G. mellonella resulted in clearly distinguishable innate immune
      responses that could be verified by analyzing similar innate immune components in
      mice in vivo and in vitro. The differential innate immune responses were
      initiated by the recognition of bacterial components via pattern recognition
      receptors. The pathobiont detection resulted in increased expression of reactive
      oxygen and nitrogen species related genes as well as antimicrobial peptide gene
      expression. In contrast, the treatment/application with symbiotic bacteria led to
      weakened immune responses in both mammalian and insect models. As symbionts and
      pathobionts play a crucial role in development of inflammatory bowel diseases, we
      hence suggest G. mellonella as a future replacement organism in inflammatory
      bowel disease research.

PMID- 30283453
TI  - Comprehensively Profiling the Chromatin Architecture of Tissue Restricted Antigen
      Expression in Thymic Epithelial Cells Over Development.
AB  - Thymic epithelial cells (TEC) effect crucial roles in thymopoiesis including the
      control of negative thymocyte selection. This process depends on their capacity
      to express promiscuously genes encoding tissue-restricted antigens. This
      competence is accomplished in medullary TEC (mTEC) in part by the presence of the
      transcriptional facilitator AutoImmune REgulator, AIRE. AIRE-regulated gene
      transcription is marked by repressive chromatin modifications, including
      H3K27me3. When during TEC development these chromatin marks are established,
      however, remains unclear. Here we use a comprehensive ChIP-seq dataset of
      multiple chromatin modifications in different TEC subtypes to demonstrate that
      the chromatin landscape is established early in TEC differentiation. Much of the
      chromatin architecture found in mature mTEC was found to be present already over
      earlier stages of mTEC lineage differentiation as well as in non-TEC tissues.
      This was reflected by the fact that a machine learning approach accurately
      classified genes as AIRE-induced or AIRE-independent both in immature and mature
      mTEC. Moreover, analysis of TEC specific enhancer elements identified candidate
      transcription factors likely to be important in mTEC development and function.
      Our findings indicate that the mature mTEC chromatin landscape is laid down early
      in mTEC differentiation, and that AIRE is not required for large-scale re
      patterning of chromatin in mTEC.

PMID- 30283452
TI  - Redox-Mediated Mechanisms Fuel Monocyte Responses to CXCL12/HMGB1 in Active
      Rheumatoid Arthritis.
AB  - Chemokine synergy-inducing molecules are emerging as regulating factors in cell
      migration. The alarmin HMGB1, in its reduced form, can complex with CXCL12
      enhancing its activity on monocytes via the chemokine receptor CXCR4, while the
      form containing a disulfide bond, by binding to TLR2 or TLR4, initiates a cascade
      of events leading to production of cytokines and chemokines. So far, the
      possibility that the CXCL12/HMGB1 heterocomplex could be maintained in chronic
      inflammation was debated, due to the release of reactive oxygen species.
      Therefore, we have assessed if the heterocomplex could remain active in
      Rheumatoid Arthritis (RA) and its relevance in the disease assessment. Monocytes
      from RA patients with active disease require a low concentration of HMGB1 to
      enhance CXCL12-induced migration, in comparison to monocytes from patients in
      clinical remission or healthy donors. The activity of the heterocomplex depends
      on disease activity, on the COX2 and JAK/STAT pathways, and is determined by the
      redox potential of the microenvironment. In RA, the presence of an active
      thioredoxin system correlates with the enhanced cell migration, and with the
      presence of the heterocomplex in the synovial fluid. The present study highlights
      how, in an unbalanced microenvironment, the activity of the thioredoxin system
      plays a crucial role in sustaining inflammation. Prostaglandin E2 stimulation of
      monocytes from healthy donors is sufficient to recapitulate the response observed
      in patients with active RA. The activation of mechanisms counteracting the
      oxidative stress in the extracellular compartment preserves HMGB1 in its reduced
      form, and contributes to fuel the influx of inflammatory cells. Targeting the
      heterocomplex formation and its activity could thus be an additional tool for
      dampening the inflammation sustained by cell recruitment, for those patients with
      chronic inflammatory conditions who poorly respond to current therapies.

PMID- 30283454
TI  - Tc17/IL-17A Up-Regulated the Expression of MMP-9 via NF-kappaB Pathway in Nasal
      Epithelial Cells of Patients With Chronic Rhinosinusitis.
AB  - Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease of the
      upper airways involving nasal cavity and sinus. Deriving both from its clinical
      complexity with protean clinical manifestations as well its pathogenetic
      heterogeneity, the molecular mechanisms contributing to the pathogenesis of CRS
      remain unclear, and attract a wide interest in the field. Current evidences
      indicate that IL-17A is highly expressed in chronic rhinosinusitis with nasal
      polyps (CRSwNP). However, its pathogenetic role in regulation of tissue
      remodeling of CRSwNP remains unknown. The present study aimed to investigate the
      cellular origins and functions of IL-17A cytokine in CRSwNP, and further
      determined whether IL-17A could affect the expression of metalloproteinases
      (MMPs), the remodeling factors of CRSwNP. The results showed that the expression
      of IL-17A was upregulated in nasal tissues of patients with CRSwNP compared to
      those with chronic rhinosinusitis without nasal polyps (CRSsNP) and controls.
      CD8+ cytotoxic T lymphocytes (Tc) were major IL-17A producers in nasal tissues of
      CRSwNP. Interleukin (IL)-17-producing CD8+ T cells (Tc17) was significantly
      higher in nasal tissues of CRSwNP than CRSsNP and controls. Nonetheless, no
      difference was observed among the IL-17A in peripheral blood lymphocytes of these
      three groups. Moreover, in the same patients, IL-17A expression was negligible in
      lymphocytes of peripheral blood when compared with nasal tissues. Increased gene
      and protein expression of MMP-7 and MMP-9 in patients with CRSwNP compared with
      controls were observed. In CRSwNP samples, IL-17A receptor (IL-17AR) co-localized
      with MMP-9 and they were mainly expressed in the epithelial cells. MMP-9
      expression was up-regulated both in Primary human nasal epithelial cells (PHNECs)
      and a nasal epithelial cell line (RPMI 2650) by IL-17A treatment, and diminished
      by anti-IL-17AR treatment. Furthermore, IL-17A promoted the expression of MMP-9
      by activating the NF-kappaB signal pathway. Thus, our results have revealed a
      crucial role of IL-17A and Tc cells on pathogenesis and tissue remodeling of
      CRSwNP.

PMID- 30283455
TI  - Cerebrospinal Fluid Inflammatory Cytokine Aberrations in Alzheimer's Disease,
      Parkinson's Disease and Amyotrophic Lateral Sclerosis: A Systematic Review and
      Meta-Analysis.
AB  - It has been suggested that cytokine-mediated inflammation plays a key role for
      the onset and/or development of neurodegenerative diseases including Alzheimer's
      disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS).
      However, clinical studies have yielded inconsistent results for the aberrant
      cytokine levels in circulation of patients with AD, PD, and ALS. Previous studies
      have used meta-analysis to address the inconsistent data for blood cytokine
      levels in the patients with AD, PD, and ALS. Here, we performed a systemic review
      of cerebrospinal fluid inflammatory cytokine data in patients with AD, PD and
      ALS, and sought to quantitatively summarize the CSF inflammatory cytokine data
      with a meta-analytical technique. The systematic search from Pubmed and Web of
      Science identified 71 articles with 2629 patients and 2049 controls for the meta
      analysis. Random-effects meta-analysis demonstrated that CSF TGF-beta, MCP-1, and
      YKL-40 levels were significantly elevated in AD patients when compared with
      controls. In addition, patients with PD had heightened levels of TGF-beta1, IL-6,
      and IL-1beta in CSF. Furthermore, G-CSF, IL-2, IL-15, IL-17, MCP-1, MIP-1alpha,
      TNF-alpha, and VEGF levels were significantly increased in patients with ALS as
      compared with controls. Taken together, these results not only strengthen the
      clinical evidence that neurodegenerative diseases are accompanied by the
      increased inflammatory response, but also reveal the unique inflammatory response
      profile in the central nervous system of patients with AD, PD and ALS. Given the
      robust associations between some cytokines and neurodegenerative diseases found
      in this meta-analysis, CSF inflammatory cytokines may be used as biomarkers for
      these diseases in the future.

PMID- 30283456
TI  - Active Tuberculosis Is Characterized by Highly Differentiated Effector Memory Th1
      Cells.
AB  - Despite advances in diagnosing latent Mycobacterium tuberculosis infection
      (LTBI), we still lack a diagnostic test that differentiates LTBI from active
      tuberculosis (TB) or predicts the risk of progression to active disease. One
      reason for the absence of such a test may be the failure of current assays to
      capture the dynamic complexities of the immune responses associated with various
      stages of TB, since these assays measure only a single parameter (release of IFN
      gamma) and rely on prolonged (overnight) T cell stimulation. We describe a novel,
      semi-automated RNA flow cytometry assay to determine whether immunological
      differences can be identified between LTBI and active TB. We analyzed antigen
      induced expression of Th1 cytokine mRNA after short (2- and 6-h) stimulation with
      antigen, in the context of memory T cell immunophenotyping. IFNG and TNFA mRNA
      induction was detectable in CD4+ T cells after only 2 h of ex vivo stimulation.
      Moreover, IFNG- and TNFA-expressing CD4+ T cells (Th1 cells) were more frequent
      in active TB than in LTBI, a difference that is undetectable with conventional,
      protein-based cytokine assays. We also found that active TB was associated with
      higher ratios of effector memory to central memory Th1 cells than LTBI. This
      effector memory phenotype of active TB was associated with increased T cell
      differentiation, as defined by loss of the CD27 marker, but not with T cell
      exhaustion, as determined by PD-1 abundance. These results indicate that single
      cell-based, mRNA measurements may help identify time-dependent, quantitative
      differences in T cell functional status between latent infection and active
      tuberculosis.

PMID- 30283457
TI  - Intrinsic Programming of Alveolar Macrophages for Protective Antifungal Innate
      Immunity Against Pneumocystis Infection.
AB  - Invasive fungal infections, including Pneumocystis Pneumonia (PcP), remain
      frequent life-threatening conditions of patients with adaptive immune defects.
      While innate immunity helps control pathogen growth early during infection, it is
      typically not sufficient for complete protection against Pneumocystis and other
      human fungal pathogens. Alveolar macrophages (AM) possess pattern recognition
      molecules capable of recognizing antigenic and structural determinants of
      Pneumocystis. However, this pathogen effectively evades innate immunity to infect
      both immunocompetent and immunosuppressed hosts, albeit with differing outcomes.
      During our studies of mouse models of PcP, the FVB/N strain was identified as
      unique because of its ability to mount a protective innate immune response
      against Pneumocystis infection. In contrast to other immunocompetent strains,
      which become transiently infected prior to the onset of adaptive immunity, FVB/N
      mice rapidly eradicated Pneumocystis before an adaptive immune response was
      triggered. Furthermore, FVB/N mice remained highly resistant to infection even in
      the absence of functional T cells. The effector mechanism of innate protection
      required the action of functional alveolar macrophages, and the adoptive transfer
      of resistant FVB/N AMs, but not susceptible CB.17 AMs, conferred protection to
      immunodeficient mice. Macrophage IFNgamma receptor signaling was not required for
      innate resistance, and FVB/N macrophages were found to display markers of
      alternative activation. IFNgamma reprogrammed resistant FVB/N macrophages to a
      permissive M1 biased phenotype through a mechanism that required direct
      activation of the macrophage IFNgammaR. These results demonstrate that
      appropriately programmed macrophages provide protective innate immunity against
      this opportunistic fungal pathogen, and suggest that modulating macrophage
      function may represent a feasible therapeutic strategy to enhance antifungal host
      defense. The identification of resistant and susceptible macrophages provides a
      novel platform to study not only the mechanisms of macrophage-mediated antifungal
      defense, but also the mechanisms by which Pneumocystis evades innate immunity.

PMID- 30283460
TI  - Autoantibodies Against Perilipin 1 as a Cause of Acquired Generalized
      Lipodystrophy.
AB  - Acquired generalized lipodystrophy (AGL) is a rare condition characterized by an
      altered distribution of adipose tissue and predisposition to develop hepatic
      steatosis and fibrosis, diabetes, and hypertriglyceridemia. Diagnosis of AGL is
      based on the observation of generalized fat loss, autoimmunity and lack of family
      history of lipodystrophy. The pathogenic mechanism of fat destruction remains
      unknown but evidences suggest an autoimmune origin. Anti-adipocyte antibodies
      have been previously reported in patients with AGL, although their involvement in
      the pathogenesis has been poorly studied and the autoantibody target/s remain/s
      to be identified. Using a combination of immunochemical and cellular studies, we
      investigated the presence of anti-adipocyte autoantibodies in patients with AGL,
      acquired partial lipodystrophy, localized lipoatrophy due to intradermic insulin
      injections or systemic lupus erythematosus. Moreover, the impact of anti
      adipocyte autoantibodies from AGL patients was assessed in cultured mouse
      preadipocytes. Following this approach, we identified anti-perilipin 1 IgG
      autoantibodies in the serum of patients with autoimmune variety-AGL, but in no
      other lipodystrophies tested. These autoantibodies altered the ability of
      perilipin 1 to regulate lipolysis in cultured preadipocytes causing abnormal,
      significantly elevated basal lipolysis. Our data provide strong support for the
      conclusion that perilipin 1 autoantibodies are a cause of generalized
      lipodystrophy in these patients.

PMID- 30283458
TI  - Nematode-Infected Mice Acquire Resistance to Subsequent Infection With Unrelated
      Nematode by Inducing Highly Responsive Group 2 Innate Lymphoid Cells in the Lung.
AB  - The immune responses against helminths have been investigated individually, and
      it is well-established that infected hosts develop an immunological memory to
      resist reinfection by the same pathogen. In contrast, it is poorly understood how
      the host immune system responds to subsequent infection by unrelated parasites
      after elimination of the first infection. We previously reported that infection
      of mice with Strongyloides venezuelensis induces the accumulation of group 2
      innate lymphoid cells (ILC2s) in the lung. Here, we demonstrated that S.
      venezuelensis-experienced (Sv-exp) mice became significantly resistant against
      infection by Nippostrongylus brasiliensis. N. brasiliensis infection induced
      enhanced accumulation of ILC2s and eosinophils with increased expressions of mRNA
      for Th2 cytokines in the lungs of Sv-exp mice. The resistance was dependent on
      ILC2s, and eosinophils but not on CD4+ T cells. Furthermore, pulmonary ILC2s in
      Sv-exp mice acquired a highly responsive "trained" phenotype; in response to N.
      brasiliensis infection, they rapidly increased and produced IL-5 and IL-13, which
      in turn induced the early accumulation of eosinophils in the lungs. IL-33 was
      required for the accumulation of ILC2s and the resistance of mice against N.
      brasiliensis infection but insufficient for the induction of trained ILC2s. In
      conclusion, animals infected with one type of lung-migratory nematodes acquire a
      specific-antigen-independent resistance to another type of lung-migrating
      nematodes, providing animals with the capacity to protect against sequential
      infections with various lung-migratory nematodes.

PMID- 30283459
TI  - Genome-Wide Inhibition of Pro-atherogenic Gene Expression by Multi-STAT Targeting
      Compounds as a Novel Treatment Strategy of CVDs.
AB  - Cardiovascular diseases (CVDs), including atherosclerosis, are globally the
      leading cause of death. Key factors contributing to onset and progression of
      atherosclerosis include the pro-inflammatory cytokines Interferon (IFN)alpha and
      IFNgamma and the Pattern Recognition Receptor (PRR) Toll-like receptor 4 (TLR4).
      Together, they trigger activation of Signal Transducer and Activator of
      Transcription (STAT)s. Searches for compounds targeting the pTyr-SH2 interaction
      area of STAT3, yielded many small molecules, including STATTIC and STX-0119.
      However, many of these inhibitors do not seem STAT3-specific. We hypothesized
      that multi-STAT-inhibitors that simultaneously block STAT1, STAT2, and STAT3
      activity and pro-inflammatory target gene expression may be a promising strategy
      to treat CVDs. Using comparative in silico docking of multiple STAT-SH2 models on
      multi-million compound libraries, we identified the novel multi-STAT inhibitor,
      C01L_F03. This compound targets the SH2 domain of STAT1, STAT2, and STAT3 with
      the same affinity and simultaneously blocks their activity and expression of
      multiple STAT-target genes in HMECs in response to IFNalpha. The same in silico
      and in vitro multi-STAT inhibiting capacity was shown for STATTIC and STX-0119.
      Moreover, C01L_F03, STATTIC and STX-0119 were also able to affect genome-wide
      interactions between IFNgamma and TLR4 by commonly inhibiting pro-inflammatory
      and pro-atherogenic gene expression directed by cooperative involvement of STATs
      with IRFs and/or NF-kappaB. Moreover, we observed that multi-STAT inhibitors
      could be used to inhibit IFNgamma+LPS-induced HMECs migration, leukocyte adhesion
      to ECs as well as impairment of mesenteric artery contractility. Together, this
      implicates that application of a multi-STAT inhibitory strategy could provide
      great promise for the treatment of CVDs.

PMID- 30283461
TI  - Durable Clinical Responses and Long-Term Follow-Up of Stage III-IV Non-Small-Cell
      Lung Cancer (NSCLC) Patients Treated With IDO Peptide Vaccine in a Phase I Study
      A Brief Research Report.
AB  - Background: Long-term follow-up on a clinical trial of 15 stage III-IV NSCLC
      patients treated with an Indoleamine 2,3-Dioxygenase (IDO) peptide vaccine
      (NCT01219348). Methods: Fifteen HLA-A2-positive patients with stable stage III-IV
      NSCLC after standard chemotherapy were treated with subcutaneous vaccinations
      (100 MUg IDO5 peptide, sequence ALLEIASCL, formulated in 900 MUl Montanide)
      biweekly for 2.5 months and thereafter monthly until progression or up to 5
      years. Here we report long-term clinical follow-up, toxicity and immunity.
      Results: Three of 15 patients are still alive corresponding to a 6-year overall
      survival of 20 %. Two patients continued monthly vaccinations for 5 years (56
      vaccines). One of the two patients developed a partial response (PR) of target
      lesions in the liver 15 months after the first vaccine and has remained in PR
      ever since. The other patient had a solitary distant metastasis in a lymph node
      in retroperitoneum at baseline which normalized during treatment. All following
      evaluation scans during the treatment have been tumor free. The vaccine was well
      tolerated for all 5 years with no long-term toxicities registered. The third long
      term surviving patient discontinued vaccinations after 11 months due to disease
      progression. Flow cytometry analyses of PBMCs from the two long-term responders
      demonstrated stable CD8+ and CD4+ T-cell populations during treatment. In
      addition, presence of IDO-specific T-cells was detected by IFN-gamma Elispot in
      both patients at several time points during treatment. Conclusion: IDO peptide
      vaccination was well tolerated for administration up to 5years. Two of 15
      patients are long-term responders with ongoing clinical response 6 years after
      1st vaccination.

PMID- 30283463
TI  - Identification of Major QTLs Associated With First Pod Height and Candidate Gene
      Mining in Soybean.
AB  - First pod height (FPH) is a quantitative trait in soybean [Glycine max (L.)
      Merr.] that affects mechanized harvesting. A compatible combination of the FPH
      and the mechanized harvester is required to ensure that the soybean is
      efficiently harvested. In this study, 147 recombinant inbred lines, which were
      derived from a cross between 'Dongnong594' and 'Charleston' over 8 years, were
      used to identify the major quantitative trait loci (QTLs) associated with FPH.
      Using a composite interval mapping method with WinQTLCart (version 2.5), 11 major
      QTLs were identified. They were distributed on five soybean chromosomes, and 90
      pairs of QTLs showed significant epistatic associates with FPH. Of these, 3 were
      main QTL * main QTL interactions, and 12 were main QTL * non-main QTL
      interactions. A KEGG gene annotation of the 11 major QTL intervals revealed 8
      candidate genes related to plant growth, appearing in the pathways K14486 (auxin
      response factor 9), K14498 (serine/threonine-protein kinase), and K13946
      (transmembrane amino acid transporter family protein), and 7 candidate genes had
      high expression levels in the soybean stems. These results will aid in building a
      foundation for the fine mapping of the QTLs related to FPH and marker-assisted
      selection for breeding in soybean.

PMID- 30283462
TI  - GWAS Analysis and QTL Identification of Fiber Quality Traits and Yield Components
      in Upland Cotton Using Enriched High-Density SNP Markers.
AB  - It is of great importance to identify quantitative trait loci (QTL) controlling
      fiber quality traits and yield components for future marker-assisted selection
      (MAS) and candidate gene function identifications. In this study, two kinds of
      traits in 231 F6:8 recombinant inbred lines (RILs), derived from an intraspecific
      cross between Xinluzao24, a cultivar with elite fiber quality, and Lumianyan28, a
      cultivar with wide adaptability and high yield potential, were measured in nine
      environments. This RIL population was genotyped by 122 SSR and 4729 SNP markers,
      which were also used to construct the genetic map. The map covered 2477.99 cM of
      hirsutum genome, with an average marker interval of 0.51 cM between adjacent
      markers. As a result, a total of 134 QTLs for fiber quality traits and 122 QTLs
      for yield components were detected, with 2.18-24.45 and 1.68-28.27% proportions
      of the phenotypic variance explained by each QTL, respectively. Among these QTLs,
      57 were detected in at least two environments, named stable QTLs. A total of 209
      and 139 quantitative trait nucleotides (QTNs) were associated with fiber quality
      traits and yield components by four multilocus genome-wide association studies
      methods, respectively. Among these QTNs, 74 were detected by at least two
      algorithms or in two environments. The candidate genes harbored by 57 stable QTLs
      were compared with the ones associated with QTN, and 35 common candidate genes
      were found. Among these common candidate genes, four were possibly "pleiotropic."
      This study provided important information for MAS and candidate gene functional
      studies.

PMID- 30283465
TI  - Comprehensive Analysis of MYB Gene Family and Their Expressions Under Abiotic
      Stresses and Hormone Treatments in Tamarix hispida.
AB  - The MYB transcription factors (TFs) is a plant TF families, which involves in
      hormone signal transduction, and abiotic stress tolerance, etc. However, there
      are few studies on the MYB TFs family and its regulatory mechanism in Tamarix
      hispida. In this study, 14 MYB genes (named ThMYB1 - ThMYB14) were cloned and
      characterized from T. hispida. The transcription profiles of ThMYBs in T. hispida
      under different abiotic stress conditions were monitored using qRT-PCR. Most of
      studied ThMYBs were significantly downregulated and/or upregulated by salt and
      osmotic stress, ABA, GA3 and JA treatments in at least one organ. Especially,
      ThMYB13 was induced in the leaves and roots of T. hispida when exposed to NaCl
      treatment at all study periods, indicating that it may involve in salt stress. To
      further study ThMYB13 function, ThMYB13 overexpression and knock-down plants and
      control plants transformed with an empty pROKII were obtained using a transient
      transformation system. Overexpression of ThMYB13 in T. hispida displayed the
      lowest O2-, H2O2 and MDA accumulation, minimal cell death, the most stable K+/Na+
      ratio and the lowest electrolyte leakage rate among the three kinds of transient
      expression in T. hispida. Conversely, the RNAi-silencing, transiently transformed
      plants displayed the opposite physiological changes. Therefore, ThMYB13 might
      play a role in salt stress tolerance in transgenic T. hispida plants.

PMID- 30283464
TI  - Systematic Analysis of Cotton Non-specific Lipid Transfer Protein Family Revealed
      a Special Group That Is Involved in Fiber Elongation.
AB  - Non-specific lipid transfer proteins (nsLTPs) had been previously isolated from
      cotton fiber but their functions were unclear so far. Bioinformatic analysis of
      the tetraploid cotton genome database identified 138 nsLTP genes, falling into
      the 11 groups as reported previously. Different from Arabidopsis, cacao, and
      other crops, cotton type XI genes were considerably expanded and diverged earlier
      on chromosome At11, Dt11, and Dt08. Corresponding to the type XI genes, the type
      XI proteins (GhLtpXIs) all contained an extra N-terminal cap resulting in larger
      molecular weight. The research revealed that the expression of type XI genes was
      dramatically increased in fibers of tetraploid cotton compared with the two
      diploid progenitors. High-level of GhLtpXIs expression was observed in long
      fibered cotton cultivars during fiber elongation. Ectopic expression of GhLtpXIs
      in Arabidopsis significantly enhanced trichome length, suggesting that GhLtpXIs
      promoted fiber elongation. Overall, the findings of this research provide
      insights into phenotypic evolution of Gossypium species and regulatory mechanism
      of nsLTPs during fiber development. HIGHLIGHT A specific group, type XI nsLTPs,
      was identified with predominant expression in elongating fibers of Gossypium
      hirsutum based on evolutionary, transcriptional, and functional analyses.

PMID- 30283467
TI  - New Plant Breeding Techniques Under Food Security Pressure and Lobbying.
AB  - Different countries have different regulations for the approval and cultivation
      of crops developed by using new plant breeding technologies (NPBTs) such as gene
      editing. In this paper, we investigate the relationship between global food
      security and the level of NPBT regulation assuming a World Nation Official (WNO)
      proposes advice on global NPBT food policies. We show that a stricter NPBT food
      regulation reduces food security as measured by food availability, access, and
      utilization. We also find that political rivalry among interest groups worsens
      the food security status, given the NPBT food technology is more productive and
      the regulatory policy is influenced by lobbying. When the WNO aims to improve
      food security and weighs the NPBT food lobby contribution more than the non-NPBT
      food lobby's in the lobbying game, the total lobbying contributions will be the
      same for the WNO, and the NPBT food lobby will be more successful in the
      political process. The NPBT food lobby, however, under food security loses its
      advantage in the political competition, and this may result in a strict NPBT food
      policy. Under food security problems implementing stricter NPBT food regulations
      results in welfare losses. JEL Code: D04, D43, D72, P16.

PMID- 30283466
TI  - Harnessing the Potential of Forage Legumes, Alfalfa, Soybean, and Cowpea for
      Sustainable Agriculture and Global Food Security.
AB  - Substantial improvements in access to food and increased purchasing power are
      driving many people toward consuming nutrition-rich foods causing an
      unprecedented demand for protein food worldwide, which is expected to rise
      further. Forage legumes form an important source of feed for livestock and have
      potential to provide a sustainable solution for food and protein security.
      Currently, alfalfa is a commercially grown source of forage and feed in many
      countries. However, soybean and cowpea also have the potential to provide quality
      forage and fodder for animal use. The cultivation of forage legumes is under
      threat from changing climatic conditions, indicating the need for breeding
      cultivars that can sustain and acclimatize to the negative effects of climate
      change. Recent progress in genetic and genomic tools have facilitated the
      identification of quantitative trait loci and genes/alleles that can aid in
      developing forage cultivars through genomics-assisted breeding. Furthermore,
      transgenic technology can be utilized to manipulate the genetic makeup of plants
      to improve forage digestibility for better animal performance. In this article,
      we assess the genetic potential of three important legume crops, alfalfa,
      soybean, and cowpea in supplying quality fodder and feed for livestock. In
      addition, we examine the impact of climate change on forage quality and discuss
      efforts made in enhancing the adaptation of the plant to the abiotic stress
      conditions. Subsequently, we suggest the application of integrative approaches to
      achieve adequate forage production amid the unpredictable climatic conditions.

PMID- 30283468
TI  - Genome-Wide Identification, Characterization, and Expression Profiling of the
      Legume BZR Transcription Factor Gene Family.
AB  - The BRASSINAZOLE-RESISTANT (BZR) family of transcription factors (TFs) are
      positive regulators in the biosynthesis of brassinosteroids. The latter is a
      class of steroid hormones that affect a variety of developmental and
      physiological processes in plants. BZR TFs play essential roles in the regulation
      of plant growth and development, including multiple stress-resistance functions.
      However, the evolutionary history and individual expression patterns of the
      legume BZR genes has not been determined. In this study, we performed a genome
      wide investigation of the BZR gene family in seven legume species. In total, 52
      BZR genes were identified and characterized. By analyzing their phylogeny, we
      divided these BZR genes into five groups by comparison with orthologs/paralogs in
      Arabidopsis thaliana. The intron/exon structural patterns and conserved protein
      motifs of each gene were analyzed and showed high group-specificities. Legume BZR
      genes were unevenly distributed among their corresponding genomes. Genome and
      gene sequence comparisons revealed that gene expansion of the BZR TF family in
      legumes mainly resulted from segmental duplications and that this family has
      undergone purifying selection. Synteny analysis showed that BZR genes tended to
      localize within syntenic blocks conserved across legume genomes. The expression
      patterns of BZR genes among various legume vegetative tissues and in response to
      different abiotic stresses were analyzed using a combination of public
      transcriptome data and quantitative PCR. The patterns indicated that many BZR
      genes regulate legume organ development and differentiation, and significantly
      respond to drought and salt stresses. This study may provide valuable information
      for understanding the evolution of BZR gene structure and expression, and lays a
      foundation for future functional analysis of the legume BZR genes by species and
      by gene.

PMID- 30283469
TI  - Heat in Wheat: Exploit Reverse Genetic Techniques to Discover New Alleles Within
      the Triticum durum sHsp26 Family.
AB  - Wheat breeding nowadays must address producers and consumers' desire. According
      to the last FAO report, a dramatic decrease in wheat production is expected in
      the next decades mainly due to the upcoming climate change. The identification of
      the processes which are triggered by heat stress and how thermotolerance develops
      in wheat is an active research topic. Genomic approach may help wheat breeding
      since it allows direct study on the genotype and relationship with the phenotype.
      Here the isolation and characterization of four members of the chloroplast
      localized small heat shock proteins (sHSP) encoded by the Hsp26 gene family is
      reported. Furthermore, two high throughput TILLING (Targeting Induced Local
      Lesions In Genomes) approaches in vivo and in silico were used for the
      identification of new alleles within this family. Small heat shock proteins are
      known to prevent the irreversible aggregation of misfolded proteins and
      contribute to the acquisition of thermotolerance. Chloroplast-localized sHSPs
      protect the photosynthetic machinery during episodes of high temperature stress.
      The modulation of the newly discovered genes within the sHsp26 family has been
      analyzed in vivo and by the ExpVIP platform widening the abiotic stress analysis;
      and their involvement in the heat stress response has been demonstrated. In
      addition, in this study a total of 50 TILLING mutant lines have been identified.
      A set of KASP (Kompetitive Allele Specific PCR) markers was also developed to
      follow the specific mutations in the ongoing backcrosses, applicable to high
      throughput genotyping approaches and usable in marker assisted selection breeding
      programs.

PMID- 30283470
TI  - Bioinformatic and in vitro Analyses of Arabidopsis Starch Synthase 2 Reveal Post
      translational Regulatory Mechanisms.
AB  - Starch synthase 2 (SS2) is an important enzyme in leaf starch synthesis,
      elongating intermediate-length glucan chains. Loss of SS2 results in a distorted
      starch granule phenotype and altered physiochemical properties, highlighting its
      importance in starch biosynthesis, however, the post-translational regulation of
      SS2 is poorly understood. In this study, a combination of bioinformatic and in
      vitro analysis of recombinant SS2 was used to identify and characterize SS2 post
      translational regulatory mechanisms. The SS2 N-terminal region, comprising the
      first 185 amino acids of the mature protein sequence, was shown to be highly
      variable between species, and was predicted to be intrinsically disordered.
      Intrinsic disorder in proteins is often correlated with protein phosphorylation
      and protein-protein interactions. Recombinant Arabidopsis thaliana SS2 formed
      homodimers that required the N-terminal region, but N-terminal peptides could not
      form stable homodimers alone. Recombinant SS2 was shown to be phosphorylated by
      chloroplast protein kinases and recombinant casein kinase II at two N-terminal
      serine residues (S63, S65), but mutation of these phosphorylation sites (Ser>Ala)
      revealed that they are not required for homo-dimerization. Heteromeric enzyme
      complex (HEC) formation between SS2 and SBE2.2 was shown to be ATP-dependent.
      However, SS2 homo-dimerization and protein phosphorylation are not required for
      its interaction with SBE2.2, as truncation of the SS2 N-terminus did not disrupt
      ATP-dependent HEC assembly. SS2 phosphorylation had no affect on its catalytic
      activity. Intriguingly, the removal of the N-terminal region of SS2 resulted in a
      47-fold increase in its activity. As N-terminal truncation disrupted
      dimerization, this suggests that SS2 is more active when monomeric, and that
      transitions between oligomeric state may be a mechanism for SS2 regulation.

PMID- 30283471
TI  - The HEM Lines: A New Library of Homozygous Arabidopsis thaliana EMS Mutants and
      its Potential to Detect Meiotic Phenotypes.
AB  - Genetic screens have been crucial for deciphering many important biological
      processes, including meiosis. In Arabidopsis thaliana, previous forward screens
      have likely identified almost all the meiotic genes that when mutated lead to a
      pronounced decrease in fertility. However, the increasing number of genes
      identified in reverse genetics studies that play crucial roles in meiosis, but do
      not exhibit strong phenotypes when mutated, suggests that there are still many
      genes with meiotic function waiting to be discovered. In this study, we produced
      897 A. thaliana homozygous mutant lines using Ethyl Methyl Sulfonate (EMS)
      mutagenesis followed by either single seed descent or haploid doubling. Whole
      genome sequencing of a subset of lines showed an average of 696 homozygous
      mutations per line, 195 of which (28%) modify a protein sequence. To test the
      power of this library, we carried out a forward screen looking for meiotic
      defects by observing chromosomes at metaphase I of male meiosis. Among the 649
      lines analyzed, we identified 43 lines with meiotic defects. Of these, 21 lines
      had an obvious candidate causal mutation, namely a STOP or splicing site mutation
      in a gene previously shown to play a role in meiosis (ATM, MLH3, MLH1, MER3,
      HEI10, FLIP, ASY4, FLIP, PRD2, REC8, FANCL, and PSS1). Interestingly, this was
      the first time that six of these genes were identified in a forward screen in
      Arabidopsis (MLH3, MLH1, SGO1, PSS1, FANCL, and ASY4). These results illustrate
      the potential of this mutant population for screening for any qualitative or
      quantitative phenotype. Thus, this new mutant library is a powerful tool for
      functional genomics in A. thaliana. The HEM (Homozygote EMS Mutants) lines are
      available at the Versailles Arabidopsis stock center.

PMID- 30283472
TI  - Light-Dependent Changes in the Spatial Localization of Metabolites in
      Solenostemon scutellarioides (Coleus Henna) Visualized by Matrix-Free Atmospheric
      Pressure Electrospray Laser Desorption Ionization Mass Spectrometry Imaging.
AB  - The visualization of foliage color in plants provides immediate insight into some
      of the compounds that exist in the leaf. However, many non-colored compounds are
      also present; their cellular distributions are not readily identifiable
      optically. In this study we evaluate the applicability of mass spectrometry
      imaging (MSI) via electrospray laser desorption ionization (ELDI) to reveal the
      spatial distribution of metabolites. ELDI-MSI is a matrix free, atmospheric
      pressure ionization method that utilizes a UV laser coupled with supplemental
      ionization by electrospray. We specifically applied ELDI-MSI to determine the
      spatial distribution of metabolites in Coleus Henna half leaves that were grown
      with half-sections either fully illuminated or shaded. We monitored dynamic
      changes in the spatial distribution of metabolites in response to the change of
      illumination every 7 days for a 28 day period. A novel source-sink relationship
      was observed between the 2 halves of the experimental leaf. Furthermore, Coleus
      Henna leaves present visually recognizable sectors associated with the
      differential accumulation of flavonoids. Thus, we correlated the effect of
      differential illumination and presence or absence of flavonoids with metabolic
      changes revealed by the accumulation of carbohydrates, amino acids, and organic
      acids. The results show the potential of ELDI-MSI to provide spatial information
      for a variety of plant metabolites with little sample preparation.

PMID- 30283474
TI  - Relative Contribution of Nitrogen Absorption, Remobilization, and Partitioning to
      the Ear During Grain Filling in Chinese Winter Wheat.
AB  - Knowledge of the function of the ear as a key organ in the uptake, remobilization
      and partitioning of nitrogen is essential for understanding its contribution to
      grain filling and thus guiding future breeding strategies. In this work, four
      Chinese winter wheat genotypes were grown on a 15N-enriched nutrient solution. N
      absorption and further remobilization to the flag leaf, the ear and the mature
      grains were calculated via the 15N atom % excess. The results indicated that the
      high yields of the Chinese wheat genotype were determined by higher grain numbers
      per ear, with greater plant height and a larger ear size, while the thousand
      grain weight did not affect grain yield. In the mature grains, 66.7% of total N
      was remobilized from the pre-anthesis accumulation in the biomass, while the
      remaining 33.3% was derived from the N taken up during post-anthesis. From
      anthesis to 2 weeks after the anthesis stage, the flag leaf remobilized 3.67 mg
      of N outwards and the ear remobilized 3.87 mg of N inwards from the pre-anthesis
      accumulation in each plant. The positive correlation between ear Nrem and grain
      Nrem indicated that the ear was an important organ for providing N to the grain,
      whereas the remobilized N stream from the leaves was not correlated with grain
      Nrem, thus indicating that flag leaf N was not translocated directly to the
      grain. The grain Nrem was negatively correlated with the ear N concentration
      throughout grain filling, which suggested that higher-yielding genotypes had
      better sink activity in the ear, while Rubisco played a critical role in N
      deposition. Therefore, to improve yield potential in wheat, the N accumulation in
      the ear and the subsequent remobilization of that stored N to the grains should
      be considered. N accumulation and remobilization in the ear may at least be
      valuable for Chinese breeding programs that aim at optimizing the sink/source
      balance to improve grain filling.

PMID- 30283473
TI  - The Times They Are A-Changin': Heterochrony in Plant Development and Evolution.
AB  - Alterations in the timing of developmental programs during evolution, that lead
      to changes in the shape, or size of organs, are known as heterochrony.
      Heterochrony has been widely studied in animals, but has often been neglected in
      plants. During plant evolution, heterochronic shifts have played a key role in
      the origin and diversification of leaves, roots, flowers, and fruits.
      Heterochrony that results in a juvenile or simpler outcome is known as
      paedomorphosis, while an adult or more complex outcome is called peramorphosis.
      Mechanisms that alter developmental timing at the cellular level affect cell
      proliferation or differentiation, while those acting at the tissue or organismal
      level change endogenous aging pathways, morphogen signaling, and metabolism. We
      believe that wider consideration of heterochrony in the context of evolution will
      contribute to a better understanding of plant development.

PMID- 30283475
TI  - Evidence for the Extensive Conservation of Mechanisms of Ovule Integument
      Development Since the Most Recent Common Ancestor of Living Angiosperms.
AB  - The ovules and seeds of most angiosperm groups are enclosed by two integuments,
      whose evolutionary origins are considerably separated in time, as the inner
      integument arose over 300 million years ago (MYA) in an ancestor of all living
      seed plants, while the outer integument arose, perhaps as recently as 164 MYA, in
      an ancestor of all living angiosperms. Studies of the model angiosperm
      Arabidopsis thaliana indicate that the mechanisms of development of the inner and
      outer integuments depend on largely different sets of molecular players. However,
      it was not known, in most cases, whether these differences were already present
      in early flowering plants, or arose later in the Arabidopsis lineage. Here, we
      analyze the expression patterns of integument regulators in Amborella trichopoda,
      the likely sister to all other living angiosperms. The data obtained indicate
      that regulators of the YABBY, KANADI, and homeodomain-leucine zipper class III
      transcription factor families have largely conserved their integument-specific
      expression profiles in the Amborella and Arabidopsis lineages since the most
      recent common ancestor (MRCA) of living angiosperms. We identified only one case,
      involving the paralogous genes ETTIN and AUXIN RESPONSE FACTOR4, in which
      integument-specific expression patterns had clearly diverged between Amborella
      and Arabidopsis. We use the data obtained to partially reconstruct molecular
      mechanisms of integument development in the MRCA of living angiosperms and
      discuss our findings in the context of alternative hypotheses for the origin of
      the angiosperm outer integument.

PMID- 30283476
TI  - Multi-Environmental Trials Reveal Genetic Plasticity of Oat Agronomic Traits
      Associated With Climate Variable Changes.
AB  - Although oat cultivation around the Mediterranean basin is steadily increasing,
      its yield in these regions lags far behind those of Northern Europe. This results
      mainly from the poor adaptation of current oat cultivars to Mediterranean
      environments. Local landraces may act as reservoirs of favorable traits that
      could contribute to increase oat resilience in this region. To aid selection of
      suitable agro-climate adapted genotypes we integrated genome-wide association
      approaches with analysis of field assessed phenotypes of genetic variants and of
      the weight of associated markers across different environmental variables.
      Association models accounting for oat population structure were applied on either
      arithmetic means or best linear unbiased prediction (BLUPs) to ensure robust
      identification of associations with the agronomic traits evaluated. The meta
      analysis of the six joint environments (mega-environment) identified several
      markers associated with several agronomic traits and crown rust severity. Five of
      these associated markers were located within expressed genes. These associations
      were only mildly influenced by climatic variables indicating that these markers
      are good candidates to improve the genetic potential of oat under Mediterranean
      conditions. The models also highlighted several marker-trait associations,
      strongly affected by particular climatic variables including high rain pre- or
      post-heading dates and high temperatures, revealing strong potential for oat
      adaptation to specific agro-climatic conditions. These results will contribute to
      increase oat resilience for particular climatic conditions and facilitate
      breeding for plant adaptation to a wider range of climatic conditions in the
      current scenario of climate change.

PMID- 30283478
TI  - Stomatal Conductance and Morphology of Arbuscular Mycorrhizal Wheat Plants
      Response to Elevated CO2 and NaCl Stress.
AB  - Stomata play a critical role in the regulation of gas exchange between the
      interior of the leaf and the exterior environment and are affected by
      environmental and endogenous stimuli. This study aimed to evaluate the effect of
      the arbuscular mycorrhizal (AM) fungus, Rhizophagus irregularis, on the stomatal
      behavior of wheat (Triticum aestivum L.) plants under combination with elevated
      CO2 and NaCl stress. Wheat seedlings were exposed to ambient (400 ppm) or
      elevated (700 ppm) CO2 concentrations and 0, 1, and 2 g kg-1 dry soil NaCl
      treatments for 10 weeks. AM symbiosis increased the leaf area and stomatal
      density (SD) of the abaxial surface. Stomatal size and the aperture of adaxial
      and abaxial leaf surfaces were higher in the AM than non-AM plants under elevated
      CO2 and salinity stress. AM plants showed higher stomatal conductance (g s ) and
      maximum rate of g s to water vapor (g smax ) compared with non-AM plants.
      Moreover, leaf water potential (Psi) was increased and carbon isotope
      discrimination (Delta13C) was decreased by AM colonization, and both were
      significantly associated with stomatal conductance. The results suggest that AM
      symbiosis alters stomatal morphology by changing SD and the size of the guard
      cells and stomatal pores, thereby improving the stomatal conductance and water
      relations of wheat leaves under combined elevated CO2 and salinity stress.

PMID- 30283477
TI  - Genome Editing in Rice: Recent Advances, Challenges, and Future Implications.
AB  - Rice (Oryza sativa L.) is the major food source for more than three billion
      people of the world. In the last few decades, the classical, mutational, and
      molecular breeding approaches have brought about tremendous increase in rice
      productivity with the development of novel rice varieties. However, stagnation in
      rice yield has been reported in recent decade owing to several factors including
      the emergence of pests and phyto pathogens, climate change, and other
      environmental issues posing great threat to global food security. There is an
      urgent need to produce more rice and associated cereals to satisfy the mammoth
      task of feeding a still growing population expected to reach 9.7 billion by 2050.
      Advances in genomics and emergence of multiple genome-editing technologies
      through use of engineered site-specific nucleases (SSNs) have revolutionized the
      field of plant science and agriculture. Among them, the CRISPR/Cas9 system is the
      most advanced and widely accepted because of its simplicity, robustness, and high
      efficiency. The availability of huge genomic resources together with a small
      genome size makes rice more suitable and feasible for genetic manipulation. As
      such, rice has been increasingly used to test the efficiency of different types
      of genome editing technologies to study the functions of various genes and
      demonstrate their potential in genetic improvement. Recently developed approaches
      including CRISPR/Cpf1 system and base editors have evolved as more efficient and
      accurate genome editing tools which might accelerate the pace of crop
      improvement. In the present review, we focus on the genome editing strategies for
      rice improvement, thereby highlighting the applications and advancements of
      CRISPR/Cas9 system. This review also sheds light on the role of CRISPR/Cpf1 and
      base editors in the field of genome editing highlighting major challenges and
      future implications of these tools in rice improvement.

PMID- 30283479
TI  - Hydrogen Sulfide Mediates K+ and Na+ Homeostasis in the Roots of Salt-Resistant
      and Salt-Sensitive Poplar Species Subjected to NaCl Stress.
AB  - Non-invasive micro-test techniques (NMT) were used to analyze NaCl-altered flux
      profiles of K+, Na+, and H+ in roots and effects of NaHS (a H2S donor) on root
      ion fluxes in two contrasting poplar species, Populus euphratica (salt-resistant)
      and Populus popularis (salt-sensitive). Both poplar species displayed a net K+
      efflux after exposure to salt shock (100 mM NaCl), as well as after short-term
      (24 h), and long-term (LT) (5 days) saline treatment (50 mM NaCl, referred to as
      salt stress). NaHS (50 MUM) restricted NaCl-induced K+ efflux in roots
      irrespective of the duration of salt exposure, but K+ efflux was not pronounced
      in data collected from the LT salt stress treatment of P. euphratica. The NaCl
      induced K+ efflux was inhibited by a K+ channel blocker, tetraethylammonium
      chloride (TEA) in P. popularis root samples, but K+ loss increased with a
      specific inhibitor of plasma membrane (PM) H+-ATPase, sodium orthovanadate, in
      both poplar species under LT salt stress and NaHS treatment. This indicates that
      NaCl-induced K+ loss was through depolarization-activated K+ channels. NaHS
      caused increased Na+ efflux and a corresponding increase in H+ influx for poplar
      roots subjected to both the short- and LT salt stress. The NaHS-enhanced H+
      influx was not significant in P. euphratica samples subjected to short term salt
      stress. Both sodium orthovanadate and amiloride (a Na+/H+ antiporter inhibitor)
      effectively inhibited the NaHS-augmented Na+ efflux, indicating that the H2S
      enhanced Na+ efflux was due to active Na+ exclusion across the PM. We therefore
      conclude that the beneficial effects of H2S probably arise from upward regulation
      of the Na+/H+ antiport system (H+ pumps and Na+/H+ antiporters), which promote
      exchange of Na+ with H+ across the PM and simultaneously restricted the channel
      mediated K+ loss that activated by membrane depolarization.

PMID- 30283480
TI  - Hydrogen Sulfide Signaling in Plants: Emerging Roles of Protein Persulfidation.
AB  - Hydrogen sulfide (H2S) has been largely referred as a toxic gas and environmental
      hazard, but recent years, it has emerged as an important gas-signaling molecule
      with effects on multiple physiological processes in both animal and plant
      systems. The regulatory functions of H2S in plants are involved in important
      processes such as the modulation of defense responses, plant growth and
      development, and the regulation of senescence and maturation. The main signaling
      pathway involving sulfide has been proven to be through protein persulfidation
      (alternatively called S-sulfhydration), in which the thiol group of cysteine (
      SH) in proteins is modified into a persulfide group (-SSH). This modification may
      cause functional changes in protein activities, structures, and subcellular
      localizations of the target proteins. New shotgun proteomic approaches and
      bioinformatic analyses have revealed that persulfidated cysteines regulate
      important biological processes, highlighting their importance in cell signaling,
      since about one in 20 proteins in Arabidopsis is persulfidated. During oxidative
      stress, an increased persulfidation has been reported and speculated that
      persulfidation is the protective mechanism for protein oxidative damage.
      Nevertheless, cysteine residues are also oxidized to different post-translational
      modifications such S-nitrosylation or S-sulfenylation, which seems to be
      interconvertible. Thus, it must imply a tight cysteine redox regulation essential
      for cell survival. This review is aimed to focus on the current knowledge of
      protein persulfidation and addresses the regulation mechanisms that are disclosed
      based on the knowledge from other cysteine modifications.

PMID- 30283481
TI  - Molecular Background of Pi Deficiency-Induced Root Hair Growth in Brassica
      carinata - A Fasciclin-Like Arabinogalactan Protein Is Involved.
AB  - Formation of longer root hairs under limiting phosphate (P) conditions can
      increase the inorganic P (Pi) uptake. Here, regulatory candidate genes for Pi
      deficiency-induced root hair growth were identified by comparison of massive
      analysis of cDNA ends (MACE) provided expression profiles of two Brassica
      carinata cultivars (cv.) differing in their root hair response to Pi deficiency:
      cv. Bale develops longer root hairs under Pi deficiency, but not cv. Bacho. A
      split-root experiment was conducted for the differentiation between locally and
      systemically regulated genes. Furthermore, plants were exposed to nitrogen and
      potassium deficiency to identify P-specific reacting genes. The latter were
      knocked out by CRISPR/Cas9 and the effect on the root hair length was determined.
      About 500 genes were differentially expressed under Pi deficiency in cv. Bale,
      while these genes did not respond to the low P supply in cv. Bacho. Thirty-three
      candidate genes with a potential regulatory role were selected and the
      transcriptional regulation of 30 genes was confirmed by quantitative PCR. Only
      five candidate genes seemed to be either exclusively regulated locally (two) or
      systemically (three), whereas 25 genes seemed to be involved in both local and
      systemic signaling pathways. Potassium deficiency affected neither the root hair
      length nor the expression of the 30 candidate genes. By contrast, both P and
      nitrogen deficiency increased the root hair length, and both affected the
      transcript levels in 26 cases. However, four genes reacted specifically to Pi
      starvation. These genes and, additionally, INORGANIC PHOSPHATE TRANSPORTER 1
      (BcPHT1) were targeted by CRISPR/Cas9. However, even if the transcript levels of
      five of these genes were clearly decreased, FASCICLIN-LIKE ARABINOGALACTAN
      PROTEIN 1 (BcFLA1) was the only gene whose downregulation reduced the root hair
      length in transgenic hairy roots under Pi-deficient conditions. To the best of
      our knowledge, this is the first study describing a fasciclin-like
      arabinogalactan protein with a predicted role in the Pi deficiency-induced root
      hair elongation.

PMID- 30283482
TI  - Filter-Aided Sample Preparation Procedure for Mass Spectrometric Analysis of
      Plant Histones.
AB  - Characterization of histone post-translational modifications (PTMs) is still
      challenging, and robust histone sample preparation is essential for convincing
      evaluation of PTMs by mass spectrometry. An effective protocol for extracting
      plant histone proteins must also avoid excessive co-extraction of the numerous
      potential interfering compounds, including those related to secondary metabolism.
      Currently, the co-existence of histone marks is addressed mostly by shotgun
      proteomic analysis following chemical derivatization of histone lysine residues.
      Here, we report a straightforward approach for plant histone sample preparation
      for mass spectrometry, based on filter-aided sample preparation coupled with
      histone propionylation. The approach offers savings in sample handling and
      preparation time, enables removal of interfering compounds from the sample, and
      does not require either precipitation or dialysis of histone extract. We show the
      comparison of two protocol variants for derivatization of histone proteins, in
      solution propionylation in the vial and propionylation on the filter unit. For
      both protocols, we obtained identical abundances of post-translationally modified
      histone peptides. Although shorter time is required for histone protein labeling
      on the filter unit, in-solution derivatization slightly outweighed filter-based
      variant by lower data variability. Nevertheless, both protocol variants appear to
      be efficient and convenient approach for preparation of plant histones for mass
      spectrometric analysis.

PMID- 30283483
TI  - Hydrogen Sulfide: A Potent Tool in Postharvest Fruit Biology and Possible
      Mechanism of Action.
AB  - Hydrogen sulfide (H2S), an endogenous gaseous molecule, is considered as a
      signaling agent, in parallel with other low molecular weight reactive substances,
      mainly hydrogen peroxide (H2O2) and nitric oxide (NO), in various plant systems.
      New studies are now revealing that the postharvest application of H2S, through
      H2S donors such as sodium hydrosulfide (NaSH) or sodium sulfide (Na2S), can
      inhibit fruit ripening and senescence programs in numerous fruits. We discuss
      here current knowledge on the impact of H2S in postharvest physiology of several
      climacteric and non-climacteric fruits such as banana, apple, pear, kiwifruit,
      strawberry, mulberry fruit, and grape. Although there is still a considerable
      lack of studies establishing the mechanisms by which H2S signaling is linked to
      fruit metabolism, we highlight several candidate mechanisms, including a putative
      cross-talk between H2S and ethylene, reactive oxygen and nitrogen species,
      oxidative/nitrosative stress signaling, sulfate metabolism, and post
      translational modification of protein cysteine residues (S-sulfhydration) as
      being functional in this H2S postharvest action. Understanding H2S metabolism and
      signaling during postharvest storage and the interplay with other key player
      molecules would therefore provide new, improved strategies for better fruit
      postharvest storage. To achieve this understanding, postharvest fruit physiology
      research will need to focus increasingly on the spatial interaction between H2S
      and ethylene perception as well as on the interplay between S
      sulfhydration/desulfhydration and S-nitrosylation/denitrosylation under several
      postharvest conditions.

PMID- 30283485
TI  - Harnessing Phenotypic Plasticity to Improve Maize Yields.
AB  - Plants can produce different phenotypes when exposed to different environments.
      Understanding the genetic basis of these plastic responses is crucial for crop
      breeding efforts. We discuss two recent studies that suggest that yield
      plasticity in maize has been under selection but is controlled by different genes
      than yield.

PMID- 30283484
TI  - Extremophiles as a Model of a Natural Ecosystem: Transcriptional Coordination of
      Genes Reveals Distinct Selective Responses of Plants Under Climate Change
      Scenarios.
AB  - The goal of this research was to generate networks of co-expressed genes to
      explore the genomic responses of Rhizophora mangle L. populations to contrasting
      environments and to use gene network analysis to investigate their capacity for
      adaptation in the face of historical and future perturbations and climatic
      changes. RNA sequencing data were generated for R. mangle samples collected under
      field conditions from contrasting climate zones in the equatorial and subtropical
      regions of Brazil. A gene co-expression network was constructed using Pearson's
      correlation coefficient, showing correlations among 78,364 transcriptionally
      coordinated genes. Each region exhibited two distinct network profiles; genes
      correlated with the oxidative stress response showed higher relative expression
      levels in subtropical samples than in equatorial samples, whereas genes
      correlated with the hyperosmotic salinity response, heat response and UV response
      had higher expression levels in the equatorial samples than in the subtropical
      samples. In total, 992 clusters had enriched ontology terms, which suggests that
      R. mangle is under higher stress in the equatorial region than in the subtropical
      region. Increased heat may thus pose a substantial risk to species diversity at
      the center of its distribution range in the Americas. This study, which was
      performed using trees in natural field conditions, allowed us to associate the
      specific responses of genes previously described in controlled environments with
      their responses to the local habitat where the species occurs. The study reveals
      the effects of contrasting environments on gene expression in R. mangle, shedding
      light on the different abiotic variables that may contribute to the genetic
      divergence previously described for the species through the use of simple
      sequence repeats (SSRs). These effects may result from two fundamental processes
      in evolution, namely, phenotypic plasticity and natural selection.

PMID- 30283486
TI  - An Effective Way of Producing Fully Assembled Antibody in Transgenic Tobacco
      Plants by Linking Heavy and Light Chains via a Self-Cleaving 2A Peptide.
AB  - Therapeutic monoclonal antibodies (mAbs) have evolved into an important class of
      effective medicine in treatment of various diseases. Since the antibody molecule
      consists of two identical heavy chains (HC) and two light chains (LC), each chain
      encoded by two different genes, their expressions at similar levels are critical
      for efficient assembly of functional recombinant mAbs. Although the plant-based
      expression system has been tested to produce fully assembled recombinant mAbs,
      coordinately expressing HC and LC at similar levels in a transgenic plant remains
      a challenge. A sequence coding for a foot-and-mouth disease virus (FMDV) 2A
      peptide has been successfully used to link two or more genes, which enable the
      translated polyprotein to be "self-cleaved" into individual protein in various
      genetically modified organisms. In the present study, we exploited the usage of
      F2A in Ebola virus monoclonal antibody (EBOV mAb) production. We found that
      transgenic tobacco plants carrying a transcription unit containing HC and LC
      linked by 2A not only produced similar levels of HC and LC but also rendered a
      higher yield of fully assembled EBOV mAb compared to those expressing HC and LC
      in two independent transcription units. Purified EBOV mAb bound to an Ebola
      epitope peptide with apparent Kd -values of 90.13-149.2 nM, indicating its proper
      assembly and high affinity binding to Ebola epitope peptide. To our knowledge,
      this is the first report showing mAb production by overexpressing a single
      transcription unit consisting of HC, LC and 2A in stable transformed tobacco
      plants.

PMID- 30283488
TI  - Production of Low-Potassium Content Melon Through Hydroponic Nutrient Management
      Using Perlite Substrate.
AB  - Chronic kidney disease patients are restricted to foods with high potassium
      content but our daily diets including melon are rich in potassium. Therefore, we
      investigated the production of low-potassium melon through hydroponic nutrient
      management in soilless culture using perlite substrate during autumn season of
      2012, 2014 and spring season of 2016. In the first study, melon plants were
      supplied with 50% standard 'Enshi' nutrient solution until first 2 weeks of
      culture. In 3rd and 4th week, amount of applied potassium was 50, 75, 100, and
      125% of required potassium nitrate for each plant per week (based on our previous
      study). It was found that, melon plants grown with 50% of its required potassium
      nitrate produced fruits with about 53% low-potassium compared to control. In the
      following study, four cultivars viz. Panna, Miyabi shunjuukei, Miyabi akifuyu412,
      and Miyabi soushun banshun309 were evaluated for their relative suitability of
      low-potassium melon production. Results showed insignificant difference in fruit
      potassium content among the cultivars used. Source of potassium fertilizer as
      potassium nitrate and potassium sulfate and their restriction (from 1 or 2 weeks
      after anthesis) were also studied. There were no influences on fruit potassium
      content and yield due to sources of potassium fertilizer and restriction timings.
      In our previous studies, it was evident that potassium can be translocated from
      leaves to fruits at maturity when it was supplied nutrient without potassium.
      Thus, we also studied total number of leaves per plant (23, 24, 25, 26, and 27
      leaves per plant). It was evident that fruit potassium, yield, and quality were
      not influenced significantly due to differences in number of leaves per plant.
      These studies showed that restriction of potassium nitrate in the culture
      solution from anthesis to harvest could produce melon fruits with low-potassium
      (>20%) content compared to potassium content of greenhouse grown melon (340
      mg/100 g FW). Quality testing and clinical validation of low-potassium melon also
      showed positive responses compared to greenhouse grown melon.

PMID- 30283489
TI  - Characterization of Fructan Metabolism During Jerusalem Artichoke (Helianthus
      tuberosus L.) Germination.
AB  - The inulin-type fructans in Jerusalem artichoke (Helianthus tuberosus L.) tubers
      exhibit different degrees of polymerization and are critical for germination. We
      aimed to characterize the sugar metabolism dynamics in the tubers without bud
      eyes or shoots (T) and BE/S of indoor- and field-grown Jerusalem artichokes
      during germination. Ht1-FEH II and Ht1-FEH III (1-fructan exohydrolases II and
      III, inulin-degrading enzymes) expression increased 5 days after planting
      indoors, whereas Ht1-FEH II expression increased 72 days after planting in the
      field in T and BE/S. Ht1-SST (sucrose:sucrose 1-fructosyl transferase, inulin
      synthesis initiator), and Ht1-FFT (fructan:fructan 1-fructosyl transferase,
      inulin elongator) expression generally decreased in indoor-grown T. The enzyme
      activities of 1-FEH and 1-FFT were unchanged during germination in both indoor-
      and field-grown T and BE/S, whereas 1-SST activity decreased in indoor-grown T,
      while 1-FEH and 1-FFT activities increased as a function of germination time in
      BE/S of both indoor- and field-grown tubers. The total soluble sugar content
      gradually decreased in T after germination indoors or in the field, while at the
      end of germination, the sucrose and fructan contents decreased, and fructose
      content increased in the field. The enzyme activities of soluble vacuolar (VI) or
      neutral invertase (NI) did not change significantly, except at the late
      germination stage. Sucrose synthase (SS) and sucrose-phosphate synthase (SPS)
      activities were not significantly changed in T and BE/S in indoor-grown
      artichokes, while SS activity gradually increased, and SPS activity gradually
      decreased in field-grown artichokes, alongside sucrose degradation. Compared to
      T, BE/S generally had higher enzyme activities of 1-FEH and 1-FFT, promoting
      inulin hydrolysis. This work shows that the process of tuber germination is
      similar indoors and in the field, and germination studies can therefore be
      conducted in either environment.

PMID- 30283487
TI  - The Role of Persulfide Metabolism During Arabidopsis Seed Development Under Light
      and Dark Conditions.
AB  - The sulfur dioxygenase ETHE1 oxidizes persulfides in the mitochondrial matrix and
      is involved in the degradation of L-cysteine and hydrogen sulfide. ETHE1 has an
      essential but as yet undefined function in early embryo development of
      Arabidopsis thaliana. In leaves, ETHE1 is strongly induced by extended darkness
      and participates in the use of amino acids as alternative respiratory substrates
      during carbohydrate starvation. Thus, we tested the effect of darkness on seed
      development in an ETHE1 deficient mutant in comparison to the wild type. Since
      ETHE1 knock-out is embryo lethal, the knock-down line ethe1-1 with about 1%
      residual sulfur dioxygenase activity was used for this study. We performed
      phenotypic analysis, metabolite profiling and comparative proteomics in order to
      investigate the general effect of extended darkness on seed metabolism and
      further define the specific function of the mitochondrial sulfur dioxygenase
      ETHE1 in seeds. Shading of the siliques had no morphological effect on
      embryogenesis in wild type plants. However, the developmental delay that was
      already visible in ethe1-1 seeds under control conditions was further enhanced in
      the darkness. Dark conditions strongly affected seed quality parameters of both
      wild type and mutant plants. The effect of ETHE1 knock-down on amino acid
      profiles was clearly different from that found in leaves indicating that in seeds
      persulfide oxidation interacts with alanine and glycine rather than branched
      chain amino acid metabolism. Sulfur dioxygenase deficiency led to defects in
      endosperm development possibly due to alterations in the cellularization process.
      In addition, we provide evidence for a potential role of persulfide metabolism in
      abscisic acid (ABA) signal transduction in seeds. We conclude that the knock-down
      of ETHE1 causes metabolic re-arrangements in seeds that differ from those in
      leaves. Putative mechanisms that cause the aberrant endosperm and embryo
      development are discussed.

PMID- 30283490
TI  - Characterization and Expression Patterns of Auxin Response Factors in Wheat.
AB  - Auxin response factors (ARFs) are important transcription factors involved in
      both the auxin signaling pathway and the regulatory development of various plant
      organs. In this study, 23 TaARF members encoded by a total of 68 homeoalleles
      were isolated from 18 wheat chromosomes (excluding chromosome 4). The TaARFs,
      including their conserved domains, exon/intron structures, related microRNAs, and
      alternative splicing (AS) variants, were then characterized. Phylogenetic
      analysis revealed that members of the TaARF family share close homology with ARFs
      in other grass species. qRT-PCR analyses revealed that 20 TaARF members were
      expressed in different organs and tissues and that the expression of some members
      significantly differed in the roots, stems, and leaves of wheat seedlings in
      response to exogenous auxin treatment. Moreover, protein network analyses and co
      expression results showed that TaTIR1-TaARF15/18/19-TaIAA13 may interact at both
      the protein and genetic levels. The results of subsequent evolutionary analyses
      showed that three transcripts of TaARF15 in the A subgenome of wheat exhibited
      high evolutionary rate and underwent positive selection. Transgenic analyses
      indicated that TaARF15-A.1 promoted the growth of roots and leaves of Arabidopsis
      thaliana and was upregulated in the overexpression plants after auxin treatment.
      Our results will provide reference information for subsequent research and
      utilization of the TaARF gene family.

PMID- 30283491
TI  - De novo Assembly and Transcriptome Characterization of Opisthopappus (Asteraceae)
      for Population Differentiation and Adaption.
AB  - Opisthopappus Shih (Asteraceae), an endangered genus endemic to the Taihang
      Mountains of China, is a high-value ornamental and medicinal plant consisting of
      two species, Opisthopappus longilobus shih and Opisthopappus taihangensis (Ling)
      Shih. However, the evolutionary relationships and the taxonomic characteristics
      between the two species remain unknown. In this study, high-throughput
      transcriptome sequencing was used to analyze the differential metabolic activity
      and gene expression and screened special molecular markers for exploring the
      genetic variation and species differentiation in Opisthopappus Shih. The results
      showed that 33,974 unigenes with an average size of 801 bp were obtained with
      optimization of de novo assembly. The comprehensive functional annotation based
      on Gene Ontology (GO), Cluster of Orthologous Group (COG) and Kyoto Encyclopedia
      of Genes and Genomes pathway database (KEGG) revealed that these unigenes were
      mainly related to many physiological, metabolic, and molecular processes.
      Furthermore, the comparative transcriptome analysis indicated that 3,410
      differentially expressed genes were mainly involved in lipid, carbohydrate and
      amino acid metabolism, xenobiotics biodegradation and metabolism as well as
      environment adaptation via KEGG. Such as the CYP710A, GST, HSP90A and so on,
      could be the potential candidate genes for further investigating the molecular
      mechanism of physiological variations between O. taihangensis and O. longilobus.
      In addition, the potential 71,804 high quality single nucleotide polymorphisms
      (SNPs) and 1,444 simple sequence repeats (SSRs) were estimated. Based on the
      predicted SNP, we have developed eight SNP markers for population genetic
      analysis in Opisthopappus Shih. A significantly high level of genetic
      differentiation between the populations of O. longilobus and O. taihangensis were
      found, and they were clearly grouped into two distinct genetic clusters. These
      results conformed to the record of Flora Reipublicae Popularis Sinicae (FRPS) and
      unsupported the taxonomic status in the Flora of China. The transcriptome
      analysis of Opisthopappus Shih can contribute to in-depth exploring of internal
      mechanisms in species variation and differentiation based on molecular evidence.
      With the rich and valuable data resources, the more novel structural, functional,
      and comparative genomic studies will provide comprehensive insights into the
      evolutionary relationships between O. taihangensis and O. longilobus.

PMID- 30283493
TI  - Genome-Wide and Trait-Specific Markers: A Perspective in Designing Conservation
      Programs.
AB  - Nowadays, breed conservation has entered the genomics era and it is imperative to
      develop novel theory to design the breeding schemes of the conservation
      populations by using the genomic information. The genome-wide markers have been
      regarded as a useful strategy to maintain genetic diversity. However, using the
      genome-wide SNPs to optimize diversity might not be optimal for some specific
      loci associated with specific-traits. Using the sequencing data of the conserved
      population of the Saba pig breed, we demonstrated that the conservation program
      designed by using the genome-wide SNPs might result in the loss of the genetic
      diversity of the reproduction trait. We suggested an idea of using phylogenetic
      tree to select valuable individuals for conservation program based on the genome
      wide and trait-specific makers. The selection rule was to make the selected
      samples to be widely distributed as much as possible in both the genome-wide and
      trait-specific phylogenetic trees.

PMID- 30283492
TI  - Genome-Wide Association Analysis With a 50K Transcribed Gene SNP-Chip Identifies
      QTL Affecting Muscle Yield in Rainbow Trout.
AB  - Detection of coding/functional SNPs that change the biological function of a gene
      may lead to identification of putative causative alleles within QTL regions and
      discovery of genetic markers with large effects on phenotypes. This study has two
      fold objectives, first to develop, and validate a 50K transcribed gene SNP-chip
      using RNA-Seq data. To achieve this objective, two bioinformatics pipelines, GATK
      and SAMtools, were used to identify ~21K transcribed SNPs with allelic imbalances
      associated with important aquaculture production traits including body weight,
      muscle yield, muscle fat content, shear force, and whiteness in addition to
      resistance/susceptibility to bacterial cold-water disease (BCWD). SNPs ere
      identified from pooled RNA-Seq data collected from ~620 fish, representing 98
      families from growth- and 54 families from BCWD-selected lines with divergent
      phenotypes. In addition, ~29K transcribed SNPs without allelic-imbalances were
      strategically added to build a 50K Affymetrix SNP-chip. SNPs selected included
      two SNPs per gene from 14K genes and ~5K non-synonymous SNPs. The SNP-chip was
      used to genotype 1728 fish. The average SNP calling-rate for samples passing
      quality control (QC; 1,641 fish) was >= 98.5%. The second objective of this study
      was to test the feasibility of using the new SNP-chip in GWA (Genome-wide
      association) analysis to identify QTL explaining muscle yield variance. GWA study
      on 878 fish (representing 197 families from 2 consecutive generations) with
      muscle yield phenotypes and genotyped for 35K polymorphic markers (passing QC)
      identified several QTL regions explaining together up to 28.40% of the additive
      genetic variance for muscle yield in this rainbow trout population. The most
      significant QTLs were on chromosomes 14 and 16 with 12.71 and 10.49% of the
      genetic variance, respectively. Many of the annotated genes in the QTL regions
      were previously reported as important regulators of muscle development and cell
      signaling. No major QTLs were identified in a previous GWA study using a 57K
      genomic SNP chip on the same fish population. These results indicate improved
      detection power of the transcribed gene SNP-chip in the target trait and
      population, allowing identification of large-effect QTLs for important traits in
      rainbow trout.

PMID- 30283494
TI  - Genomic Selection for Growth Traits in Pacific Oyster (Crassostrea gigas):
      Potential of Low-Density Marker Panels for Breeding Value Prediction.
AB  - Pacific oysters are a key aquaculture species globally, and genetic improvement
      via selective breeding is a major target. Genomic selection has the potential to
      expedite genetic gain for key target traits of a breeding program, but has not
      yet been evaluated in oyster. The recent development of SNP arrays for Pacific
      oyster (Crassostrea gigas) raises the opportunity to test genomic selection
      strategies for polygenic traits. In this study, a population of 820 oysters
      (comprising 23 full-sibling families) were genotyped using a medium density SNP
      array (23 K informative SNPs), and the genetic architecture of growth-related
      traits [shell height (SH), shell length (SL), and wet weight (WW)] was evaluated.
      Heritability was estimated to be moderate for the three traits (0.26 +/- 0.06 for
      SH, 0.23 +/- 0.06 for SL and 0.35 +/- 0.05 for WW), and results of a GWAS
      indicated that the underlying genetic architecture was polygenic. Genomic
      prediction approaches were used to estimate breeding values for growth, and
      compared to pedigree based approaches. The accuracy of the genomic prediction
      models (GBLUP) outperformed the traditional pedigree approach (PBLUP) by ~25% for
      SL and WW, and ~30% for SH. Further, reduction in SNP marker density had little
      impact on prediction accuracy, even when density was reduced to a few hundred
      SNPs. These results suggest that the use of genomic selection in oyster breeding
      could offer benefits for the selection of breeding candidates to improve complex
      economic traits at relatively modest cost.

PMID- 30283495
TI  - Genome Sequence of Peacock Reveals the Peculiar Case of a Glittering Bird.
AB  - The unique ornamental features and extreme sexual traits of Peacock have always
      intrigued scientists and naturalists for centuries. However, the genomic basis of
      these phenotypes are yet unknown. Here, we report the first genome sequence and
      comparative analysis of peacock with the high quality genomes of chicken, turkey,
      duck, flycatcher and zebra finch. Genes involved in early developmental pathways
      including TGF-beta, BMP, and Wnt signaling, which have been shown to be involved
      in feather patterning, bone morphogenesis, and skeletal muscle development,
      revealed signs of adaptive evolution and provided useful clues on the phenotypes
      of peacock. Innate and adaptive immune genes involved in complement system and T
      cell response also showed signs of adaptive evolution in peacock suggesting their
      possible role in building a robust immune system which is consistent with the
      predictions of the Hamilton-Zuk hypothesis. This study provides novel genomic and
      evolutionary insights into the molecular understanding toward the phenotypic
      evolution of Indian peacock.

PMID- 30283496
TI  - Reciprocal Regulation of Metabolic Reprogramming and Epigenetic Modifications in
      Cancer.
AB  - Cancer cells reprogram their metabolism to meet their demands for survival and
      proliferation. The metabolic plasticity of tumor cells help them adjust to
      changes in the availability and utilization of nutrients in the microenvironment.
      Recent studies revealed that many metabolites and metabolic enzymes have non
      metabolic functions contributing to tumorigenesis. One major function is
      regulating epigenetic modifications to facilitate appropriate responses to
      environmental cues. Accumulating evidence showed that epigenetic modifications
      could in turn alter metabolism in tumors. Although a comprehensive understanding
      of the reciprocal connection between metabolic and epigenetic rewiring in cancer
      is lacking, some conceptual advances have been made. Understanding the link
      between metabolism and epigenetic modifications in cancer cells will shed lights
      on the development of more effective cancer therapies.

PMID- 30283498
TI  - Aspergillus flavus resident in Kenya: High genetic diversity in an ancient
      population primarily shaped by clonal reproduction and mutation-driven evolution.
AB  - Aspergillus flavus has long been considered to be an asexual species. Although a
      sexual stage was recently reported for this species from in vitro studies, the
      amount of recombination ongoing in natural populations and the genetic distance
      across which meiosis occurs is largely unknown. In the current study, genetic
      diversity, reproduction and evolution of natural A. flavus populations endemic to
      Kenya were examined. A total of 2744 isolates recovered from 629 maize-field
      soils across southern Kenya in two consecutive seasons were characterized at 17
      SSR loci, revealing high genetic diversity (9-72 alleles/locus and 2140
      haplotypes). Clonal reproduction and persistence of clonal lineages predominated,
      with many identical haplotypes occurring in multiple soil samples and both
      seasons. Genetic analyses predicted three distinct lineages with linkage
      disequilibrium and evolutionary relationships among haplotypes within each
      lineage suggesting mutation-driven evolution followed by clonal reproduction. Low
      genetic differentiation among adjacent communities reflected frequent short
      distance dispersal.

PMID- 30283497
TI  - Functional Interaction Between BRCA1 and DNA Repair in Yeast May Uncover a Role
      of RAD50, RAD51, MRE11A, and MSH6 Somatic Variants in Cancer Development.
AB  - In this study, we determined if BRCA1 partners involved in DNA double-strand
      break (DSB) and mismatch repair (MMR) may contribute to breast and ovarian cancer
      development. Taking advantage the functional conservation of DNA repair pathways
      between yeast and human, we expressed several BRCA1 missense variants in DNA
      repair yeast mutants to identify functional interaction between BRCA1 and DNA
      repair in BRCA1-induced genome instability. The pathogenic p.C61G, pA1708E,
      p.M775R, and p.I1766S, and the neutral pS1512I BRCA1 variants increased intra
      chromosomal recombination in the DNA-repair proficient strain RSY6. In the mre11,
      rad50, rad51, and msh6 deletion strains, the BRCA1 variants p.C61G, pA1708E,
      p.M775R, p.I1766S, and pS1215I did not increase intra-chromosomal recombination
      suggesting that a functional DNA repair pathway is necessary for BRCA1 variants
      to determine genome instability. The pathogenic p.C61G and p.I1766S and the
      neutral p.N132K, p.Y179C, and p.N550H variants induced a significant increase of
      reversion in the msh2Delta strain; the neutral p.Y179C and the pathogenic
      p.I1766S variant induced gene reversion also, in the msh6Delta strain. These
      results imply a functional interaction between MMR and BRCA1 in modulating genome
      instability. We also performed a somatic mutational screening of MSH6, RAD50,
      MRE11A, and RAD51 genes in tumor samples from 34 patients and identified eight
      pathogenic or predicted pathogenic rare missense variants: four in MSH6, one in
      RAD50, one in MRE11A, and two in RAD51. Although we found no correlation between
      BRCA1 status and these somatic DNA repair variants, this study suggests that
      somatic missense variants in DNA repair genes may contribute to breast and
      ovarian tumor development.

PMID- 30283499
TI  - Rifaximin has the potential to prevent complications of cirrhosis.
AB  - Background: Cirrhosis-related complications are associated with poor prognosis.
      With our analyses, we examined the potential benefit of rifaximin in reducing the
      risk of developing cirrhosis-related complications. Methods: Adults with
      cirrhosis and hepatic encephalopathy (HE) in remission were randomly assigned to
      receive rifaximin 550 mg twice daily or placebo for 6 months with concomitant
      lactulose permitted. Post hoc analyses examined time to cirrhosis-related
      complications (HE, spontaneous bacterial peritonitis (SBP), variceal bleeding,
      acute kidney injury/hepatorenal syndrome). Subgroup analyses evaluated efficacy
      for select baseline disease characteristics. Results: Of patients receiving
      rifaximin (n = 140) and placebo (n = 159), 53.6% and 49.1%, respectively, had
      baseline Model for End-Stage Liver Disease (MELD) score ? 12 and international
      normalized ratio (INR) ? 1.2. Baseline ascites was observed in 36.4% (rifaximin)
      and 34.6% (placebo) of patients. In patients with MELD score ? 12 and INR ? 1.2,
      rifaximin reduced the relative risk (RR) of any first complication experienced
      during trial by 59% [hazard ratio (HR) = 0.41, 95% confidence interval (CI): 0.25
      0.67; p < 0.001] versus placebo. For patients with baseline ascites, rifaximin
      reduced the RR of any first complication experienced during trial by 42% versus
      placebo (HR = 0.58, 95% CI: 0.34-1.0; p = 0.045). For some subgroups, there was a
      decrease in RR of complications of SBP, variceal bleeding, and acute kidney
      injury/hepatorenal syndrome with rifaximin versus placebo, although there were
      few events reported in the study. Conclusion: Rifaximin may reduce the incidence
      of cirrhosis-related complications and the recurrence of overt
      HE.[ClinicalTrials.gov identifier: NCT00298038.].

PMID- 30283501
TI  - Design and development of a biorelevant simulated human lung fluid.
AB  - Biorelevant fluids are required to enable meaningful in vitro experimental
      determinations of the biopharmaceutical properties of inhaled medicines, e.g.
      drug solubility, particle dissolution, cellular uptake. Our aim was to develop a
      biorelevant simulated lung fluid (SLF) with a well-defined composition and
      evidence-based directions for use. The SLF contained
      dipalmitoylphosphotidylcholine, dipalmitoylphosphatidylglycerol, cholesterol,
      albumin, IgG, transferrin and antioxidants. Freshly made SLF had pH 7.2,
      viscosity 1.138 * 10-3 Pa s, conductivity 14.5 mS/m, surface tension 54.9 mN/m
      and density 0.999 g/cm3. Colour, surface tension and conductivity were the most
      sensitive indicators of product deterioration. The simulant was stable for 24 h
      and 48 h at 37  degrees C and 21  degrees C, respectively, (in-use stability) and
      for 14 days when stored in a refrigerator (storage stability). To extend
      stability, the SLF was vacuum freeze-dried in batches to produce lyophilised
      powder that can be reconstituted readily when needed at the point of use. In
      conclusion, we have reported the composition and manufacture of a biorelevant,
      synthetic SLF, provided a detailed physico-chemical characterisation and
      recommendations for how to store and use a product that can be used to generate
      experimental data to provide inputs to computational models that predict drug
      bioavailability in the lungs.

PMID- 30283500
TI  - Choices for long-term hypertensive control in patients after first-ever
      hemorrhagic stroke: a nationwide cohort study.
AB  - Background: To compare the long-term clinical outcomes of different
      antihypertensive drugs in stable patients after acute hemorrhagic stroke (HS).
      Methods: From January 2001 to December 2013, patients with first-ever primary HS
      were identified in the National Health Insurance Research Database, Taiwan.
      Patients with traumatic intracerebral hemorrhage and secondary HS were excluded.
      Those with first-ever HS were recruited and classified into three groups: (1)
      angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB);
      (2) calcium channel blocker (CCB); and (3) other antihypertensive drugs
      (comparison) groups. Propensity score matching was used to balance the
      distribution of baseline characteristics, stroke severity, and medications
      between any two of the three groups. A validation study was performed using the
      databank of the Stroke Registry in Chang-Gung Healthcare System to reduce the
      bias. Primary outcomes were recurrent HS, ischemic stroke, any stroke, and all
      cause mortality. Results: Compared to the comparison group, the ACEI/ARB group
      [35.4% versus 39.3%; hazard ratio (HR), 0.84; 95% confidence interval (CI), 0.74
      0.95] and CCB group (33.0% versus 41.9%; HR, 0.72; 95% CI, 0.64-0.81) had a lower
      risk of all-cause mortality during long-term follow up. The CCB group had a
      similar risk of all-cause mortality to the ACEI/ARB group. Risks of recurrent HS,
      ischemic stroke, or any stroke were not different between the study groups.
      Conclusions: Antihypertensive drug class could be important to long-term outcomes
      in HS patients in addition to the target control of blood pressure. Both
      ACEIs/ARBs and CCBs are associated with lower risks of all-cause mortality. Our
      results may be applied to inform future research on hypertensive control in HS
      patients.

PMID- 30283502
TI  - Adenosine-induced Flow Arrest to Facilitate Intracranial Complex Aneurysm Clip
      Ligation: Review of the Literature.
AB  - Complex intracranial aneurysms (CIAs) rank high among the most technically
      demanding neurosurgical pathologies. Microsurgery and clip ligation can be
      challenging in CIAs as circumferential visualization of the aneurysm, parent
      vessels, branches, perforators, and other neurovascular structures is important
      to prevent residual aneurysms or strokes from vessel or perforator occlusion.
      Decompression of the aneurysm sac is often required for CIAs. We reviewed the
      literature and PubMed advanced search showed 13 results of adenosine-induced flow
      arrest to facilitate intracranial complex aneurysm clip ligation which included
      three independent case reports and ten cases in a case series from 1999 to May
      2016. Few case series have described the use of adenosine in intracranial
      aneurysm surgery. Satisfactory aneurysm decompression was achieved in all cases,
      and all aneurysms were clipped successfully. We recommend that adenosine cardiac
      arrest is a relatively novel method for decompression of intracranial aneurysms
      to facilitate clip application. With appropriate safety precautions, it is a
      reasonable alternative method when temporary clipping of proximal vessels is not
      desirable or not possible.

PMID- 30283504
TI  - Recovery of Oculomotor Nerve Palsy after Endovascular and Surgical Treatment of
      Posterior Communicating Artery Aneurysms: A Single Institutional Experience.
AB  - Introduction: Surgical oculomotor nerve palsy(ONP), defined by ptosis,
      ophthalmoplegia, diplopia and pupillary dilatation, is associated with
      intracranial aneurysms, especially posterior communicating artery (PcomA)
      aneurysms. Treatment of PcomA aneurysms include endovascular coiling and surgical
      clipping. This study retrospectively compared the recovery of ONP in patients who
      underwent endovascular coiling or surgical clipping. Methods: A retrospective
      review of patients with PcomA aneurysms who presented with ONP between 1998 and
      2012 in the National Neuroscience Institute, Singapore, was performed. Inclusion
      criteria included adult patients of age above 21 who have radiologically
      confirmed PcomA aneurysms with presentation of ipsilateral ONP. The aneurysms may
      be unruptured or ruptured with WFNS grade 2 subarachnoid hemorrhage (SAH) or
      better. Only patients with completely surgically or endovascularly obliterated
      PcomA aneurysms with regular follow-up are included. Results: A total of 22
      patients were recruited. They were treated by either endovascular coiling or
      surgical clipping. The two groups of patients were demographically comparable,
      with 11 patients in each arm. 13 (59%) patients had unruptured aneurysms and 9
      (41%) had WFNS grade 2 or better SAH. 13 (59%) patients presented with complete
      ONP and 9 (41%) had partial ONP. 64% of patients who underwent surgical clipping
      had resolution of ONP completely, compared to 18% of endovascularly coiling (P =
      0.03) at 1-month follow-up. Conclusion: Compared to endovascular coiling,
      surgically clipped PcomA aneurysms are associated with a faster rate of full
      recovery of ONP.

PMID- 30283505
TI  - Pituitary Adenoma Apoplexy: Review of Personal Series.
AB  - Background: Pituitary apoplexy is a life-threatening event with unspecific
      clinical background and no standardized treatment. Materials and Methods: The
      authors retrospectively analyzed seventeen patients affected by pituitary adenoma
      apoplexy and treated in a 10-year period. Thirteen patients underwent surgery
      through transsphenoidal route while four patients have been treated
      conservatively. Results: The endoscopic surgical procedure showed a better result
      in term of complete removal of the tumor while in the "conservative" group less
      frequent evidence of hormones' deficiency has been registered. Once a residual
      lesions was observed a strict radiological follow-up is mandatory. Conclusions:
      According to dedicated literature and pre- and post-operative evidence of
      personal series, the authors try to provide an algorithm that could help in the
      standardization of the diagnostic and therapeutic pathways in patients with
      pituitary adenoma apoplexy.

PMID- 30283503
TI  - Contemporary Updates on Clinical Trials of Antiangiogenic Agents in the Treatment
      of Glioblastoma Multiforme.
AB  - Glioblastoma multiforme (GBM) has the highest rate of vascular proliferation
      among solid tumors. Angiogenesis is the central feature of rapid tumor growth in
      GBM and therefore remains an appealing therapeutic target in the treatment of
      these highly malignant tumors. Antiangiogenic therapy is emerging as an important
      adjuvant treatment. Multiple antiangiogenic agents targeting various sites in
      vascular endothelial growth factor (VEGF) and integrin pathways have been tested
      in clinical trials of newly diagnosed and recurrent GBMs. These include
      bevacizumab, enzastaurin, aflibercept, cediranib, and cilengitide. In this
      review, we discuss the current status and challenges facing clinical application
      of antiangiogenic treatment including anti-VEGF therapy and integrin pathway
      agents' therapy in glioblastoma. Here, we highlight a strong biologic rationale
      for this strategy, also focusing on integrin pathways. PubMed-indexed clinical
      trials published in English on antiangiogenic treatment of glioblastomas in the
      past 5 years were reviewed. The results of the current clinical trials of these
      agents are presented.

PMID- 30283506
TI  - Acute Subdural Hematoma Evacuation: Predictive Factors of Outcome.
AB  - Background: Acute subdural hematoma (aSDH) is a major cause of admission at
      Neurosurgical Emergency Department. Nevertheless, concerns regarding surgical
      indication in patients with multiple comorbidities, poor neurological status,
      antithrombotic therapy, and older age still persist. Therefore, a correct
      recognition of predictive outcome factors at hospital discharge is crucial to an
      appropriate neurosurgical treatment. Methods: Eighty-nine medical records of
      consecutive patients with age >=18 years old who were submitted to aSDH
      evacuation between January 2008 and May 2012 were reviewed. Demographic
      characteristics, neurological status on admission, anticoagulant or antiplatelet
      therapy, and outcome on discharge were collected. Patients with insufficient data
      concerning these variables were excluded from the study. Results: Sixty-nine
      patients were included; 52% were male; 74% were older than 65 years; 41% were
      under oral antithrombotic therapy (OAT); at admission, 54% presented with Glasgow
      coma scale (GCS) <=8; 23% were submitted to a craniectomy instead of a
      craniotomy; 26% of the patients died, 32% were dependent, and 42% were
      independent on discharge. Crude analysis revealed craniectomy, A/A pupils, GCS
      <=8 at admission statistically significant related with the worst outcome (P <
      0.05). In the adjusted evaluation only A/A pupils (P = 0.04) was associated to
      poor outcome (spontaneous etiology P = 0.052). Considering daily living
      independency at hospital discharge, either male gender (P = 0.044) and A/A pupils
      (P = 0.030) were related to the worst outcome. No effect of age in outcome was
      observed. Conclusions: Male gender and A/A pupils are associated with lower
      probability of achieving independency living at hospital discharge. A/A pupils,
      low GCS at admission, spontaneous etiology, and craniectomy were associated with
      the worst outcome. Age and OAT were not predictive factors in this series.
      Caution should be taken when considering these factors in the surgical decision.

PMID- 30283507
TI  - Relationship between Abducens Nerve Palsy and Local Hematoma in a Case Series of
      Ruptured Vertebral Artery Dissecting Aneurysm.
AB  - Background: Abducens nerve palsy associated with subarachnoid hemorrhage (SAH)
      has rarely been reported. Its frequency, mechanism of palsy, association with
      aneurysmal location, and clinical course are poorly described. The purpose of our
      study was to evaluate patients with abducens nerve palsy caused by SAH occurring
      from ruptured vertebral artery (VA) dissecting aneurysm and to find aneurysmal
      location using initial computed tomography (CT) and its association with
      clinically detected cranial nerve palsy. Methods: Fourteen patients of SAH due to
      ruptured VA dissecting aneurysm were treated at our hospital from January 2011 to
      May 2015. The clinical courses and CT findings were reviewed retrospectively.
      Results: Abducens nerve palsy was observed in 77.8% of cases after excluding
      patients with decreased levels of consciousness. Clots within the prepontine
      cistern were significantly thicker in cases of VA dissecting aneurysm than in
      case of supratentorial aneurysm (P = 0.002). Conclusion: The findings of our
      study indicated that ruptured VA dissecting aneurysms, even in cases of angio
      negative SAH, are likely to present with abducens nerve palsy.

PMID- 30283508
TI  - Utility of Computed Tomography-guided Biopsy in Evaluation of Metastatic Spinal
      Lesions.
AB  - Introduction: Computed tomography (CT)-guided biopsy of spine is currently a
      valuable diagnostic tool and effective technique for diagnosing and planning a
      proper therapeutic strategy for certain spinal lesions. The reported diagnostic
      accuracy of core biopsy ranges from 77% to 97%. Materials and Methods: We
      included all patients with spinal lesions suspicious of metastasis on magnetic
      resonance imaging, who presented between May 2012 and April 2014 and underwent CT
      guided biopsy in our study. A total of thirty patients with spinal lesions were
      evaluated. Results: Majority presented in the seventh decade of their life
      (average age = 53.93; age range = 10-72 years). Male:female ratio was 1.5:1. Pain
      was the most common presenting symptom (100%). Lumbar spine was the most common
      site of lesion followed by dorsal spine. Biopsy is the gold standard in
      histopathological evaluation of spinal lesions. Metastatic lesion was diagnosed
      in 12 (40%) cases, plasmacytoma in 12 (40%) cases, non-Hodgkin's lymphoma in 2
      (6.66%) cases, small round cell tumor in 1 (3.33%) case, nonspecific chronic
      inflammation in two patients, and necrosis with no viable cells in one patient.
      The most common malignancy to metastasize to spine was adenocarcinoma. The most
      common primary tumor of spine was plasmacytoma - multiple myeloma. Conclusion:
      CCT-guided biopsy is a safe procedure, and no procedure-related complication was
      seen in any patient.

PMID- 30283509
TI  - Evaluation of Role of Electrophysiological Studies in Patients with Lumbar Disc
      Disease.
AB  - Background: The role of the electrophysiologic studies in peripheral nerves and
      muscles of lower limbs (including paraspinal muscles) in prolapsed lumbar
      intervertebral discs has been studied with equivocal results. Pre- and post
      operative electrodiagnostic studies have not been compared much. Aims and
      Objectives: To study the role of the electrophysiologic studies in prolapsed
      lumbar/lumbosacral intervertebral discs for finding the association between
      clinical findings and electrophysiological changes and to compare the
      electrophysiologic studies pre- and post-operatively. Materials and Methods: The
      study was conducted from July 2014 to June 2016 on fifty patients who were
      admitted in the department of neurological surgery with lumbar disc prolapse and
      all these patients were subjected to surgery. Both pre- and post-operative (from
      1 to 6 months after surgery) electrophysiological studies were conducted and
      compared. Results: As per the electromyographic (EMG) abnormalities, the most
      common levels of intervertebral disc prolapse were L4-L5 and L5-S1 accounting for
      32% of cases each followed by L5-S1 level which was seen in 28% of patients with
      L2-L3, L3-L4, and L4-L5 prolapsed intervertebral disc (PIVD) and L3-L4 and L4-L5
      PIVD were seen in 4% of cases each. Of the 50 patients, EMG findings correlated
      with operative findings in 37 (74%) patients, however operative findings did not
      correlate with EMG findings in 13 (26%) patients. Conclusion: In compressive
      lesions of nerve roots (due to disc prolapsed), the EMG method has a high degree
      of accuracy in determining not only the presence of such lesions but also their
      exact location. EMG is accurate when correlated with the operative findings.

PMID- 30283510
TI  - Establishing a Training Model for Side-to-Side Anastomosis using Rat Femoral
      Vessels: Immediate and Delayed Patency.
AB  - Introduction: Side-to-side anastomoses are a relatively newer and more difficult
      technique used in neurovascular surgery for complex aneurysms/lesions. In view of
      the complex surgical technique and the infrequent clinical opportunities to
      acquire skills relevant to this surgery, laboratory training assumes great
      importance. The authors studied the feasibility of establishing a training model
      for performing side-to-side anastomosis using rat femoral vessels and compared
      the immediate and delayed patency rates in this animal model. Materials and
      Methods: After Institutional Animal Ethics Committee clearance, 16 Sprague-Dawley
      rats were used in this prospective study between August 2013 and March 2015.
      Using the standard groin incision, the femoral vessels were dissected. After
      applying temporary clamps, opening of approximately 3-4 mm (at least double the
      diameter of the wider vessel) of length was made on the facing surfaces of both
      vessels. 10-0 nylon was used for anastomosis. The clamps were released, and the
      anastomoses patency confirmed. Leg movements following the anastomoses were
      studied. The animals were subsequently sacrificed to assess delayed patency.
      Results: The immediate patency rate was 87.5% (14/16). The delayed patency rate
      (mean follow-up 209 days) was 53.8% (7/13). Three rats died during the follow-up
      period. The mean clamp duration and suturing time was 57.25 and 41.50 min in the
      first eight cases and 57.50 and 36.75 min in the last eight experiments,
      respectively. Conclusion: This animal model was found to be extremely useful for
      training in the difficult art of side-to-side anastomoses. The need of the hour
      is to establish well-planned training programs in centers with animal research
      facilities and use such models. This will promote younger colleagues and trainees
      to take up and perfect this difficult art. The present work could be used as a
      baseline study in this direction.

PMID- 30283511
TI  - Intraoperative Neurophysiological Monitoring in Surgical Treatment of Spinal
      Dural Arteriovenous Fistulas: Technique and Results.
AB  - Objective and Background: Data on intraoperative neurophysiological monitoring
      (IOM) during surgery of spinal dural arteriovenous fistulas (SDAVFs) are lacking.
      The purpose of this study was to evaluate the role of IOM during microsurgery for
      SDAVFs. Materials and Methods: From March 2007 to March 2013, 12 patients had
      microsurgery with IOM for SDAVFs. The IOM included somatosensory-evoked
      potentials, motor-evoked potentials (MEPs), and - in selected cases - D-Waves.
      All patients were evaluated at admission and at follow-up (6, 12, and 24 months)
      with Aminoff-Logue Disability Scale for Gait-Aminoff-Logue Disability Scale (G
      ALS) and Micturition-Aminoff-Logue Disability Scale (M-ALS). Statistical Analysis
      Used: Logistic regression was used for detecting the clinical risk factors
      influencing neurological functions after the treatment. Results: During surgery,
      we registered the absence of significant modifications of evoked potentials in
      nine cases (75%), while improvement of MEPs occurred in three cases (25%). No
      false-negative case was registered, and IOM predicted the absence of new
      postoperative neurological deficit in all patients. At 24-month follow-up, nine
      patients improved their overall neurological status, while three patients
      remained stable. At univariate analysis, Aminoff-Logue Disability Scales for Gait
      and Micturition (G + M-ALS) score at 24-month follow-up was directly associated
      with the duration of symptom before the surgery (P = 0.024), preoperative G-ALS
      (P = 0.02), M-ALS (P = 0.022), and G + M-ALS scores (P = 0.045), and improvement
      of IOM after occlusion of the fistula (P = 0.025). Conclusions: In our series, no
      significant worsening of evoked potentials occurred and subsequently the surgical
      strategy was not changed by IOM. However, no false-negative case was registered,
      and IOM predicted the absence of new postoperative neurological deficit in all
      patients. Patients with improvement of IOM parameters after occlusion of the
      fistula had greater chances of postsurgical improvement at the univariate
      analysis.

PMID- 30283512
TI  - Endoscopic Treatment of Hydrocephalus with Minimal Resources: Resource
      Utilization and Indigenous Innovation in Developing Countries like India.
AB  - Context: Neuroendoscopic surgeries need specialized equipments, unavailable in
      neurosurgical departments of majority of public healthcare institutions of India.
      Aims: Neuroendoscopic treatment of hydrocephalus in the setting of minimal
      resources using utilization of available resources, inter-departmental co
      ordination and indigenous innovations. Methods: Study was carried out at a public
      sector institute of India with scarce resources. Senior author (DKJ) used
      indigenously designed stainless steel working sheath along with equipments of
      'awake endoscopic intubation system' of department of neuroanesthesia and 18 cm,
      4 mm, 0 degrees  rigid telescope for neuroendoscopic surgeries for various
      intraventricular pathologies. Results: Thirty-four neuroendoscopic surgeries in
      32 patients were done over last 3 years. There were 18 males and 14 females with
      average age of 23 years. It included hydrocephalus due to tubercular meningitis
      (n = 19), neurocysticercosis (NCC) (n = 4), intra-ventricular (n = 2) and para
      ventricular (n = 2) space occupying lesions, aqueduct stenosis with (n = 2) or
      without (n = 1) shunt malfunction and one case each of pyogenic meningitis and
      right cerebellar infarction. Endoscopic third ventriculostomy (ETV) (n = 28),
      septostomy (n = 6), removals of cystic lesions (n = 3) and biopsies of
      intraventricular lesions (n = 2) were done in a total of 34 neuroendoscopic
      surgeries. Overall there were four failures of ETVs, which were managed by
      ventriculo-peritoneal shunts. Two mortalities in the study group were unrelated
      to the surgical procedures. Conclusion: Indigenous innovations and
      interdisciplinary co-ordination are the way ahead to tackle resource scarcity in
      public sector healthcare institutions of India in the scenario of plenty of
      neuroendoscopic trainings opportunities for young neurosurgeons and paucity of
      equipments required.

PMID- 30283513
TI  - Efficacy of Double Drug Impregnated Autologous Coagulum Patch versus Single Drug
      Impregnated Autologous Coagulum Patch in Postoperative Pain Management after
      Spinal Surgery.
AB  - Background: Postoperative pain and cerebrospinal fluid (CSF) leak are common
      known complications of spinal surgery, both having a synergistic effect on each
      other. Thus, both need to be dealt simultaneously. Double drug impregnated
      autologous coagulum patch (DDIAC) is a novel method which reduced both incidences
      of postoperative CSF leaks as well as pain. Methodology: Twenty-seven patients
      undergoing lumbar disc surgery without instrumentation were included and
      randomized into DDIAC and single drug impregnated autologous coagulum patch
      (SDIAC) group. The patients were assessed postoperatively with visual analog
      scale (VAS). Results: There were 21 males and 6 females in the study. Seventeen
      (63%) patients got randomized for DDIAC patch application and other 10 (37%)
      patients entered the control arm group (SDIAC) patch use. Preoperative VAS was 5
      in both the groups. The average postoperative VAS was 3.01 in DDIAC arm and 4.29
      in control arm. The average analgesic shot required in the DDIAC group was 0.41
      in 24 h and SDIAC group was 4.1 in 24 h. In DDIAC group, none of these patients
      had CSF leak from the surgical wound till discharge from the hospital. In the
      SDIAC group, one (10%, n = 10) patient had CSF leak. Conclusions: DDIAC patch was
      effective in controlling pain in the postoperative period; however, few patients
      may require analgesic shots for pain management. SDIAC patch may control some
      pain in the immediate postoperative period; however, this was not sufficient for
      a longer postoperative period.

PMID- 30283514
TI  - Relationship between the Volume Rate of Ed Coil (Ed Ratio) and Packing Density in
      Endosaccular Embolization of Cerebral Aneurysms.
AB  - Purpose: A high packing density (PD) (i.e., coil volume per aneurysm volume)
      helps prevent recanalization after endosaccular embolization of cerebral
      aneurysms. We hypothesized that the use of soft coils may be useful to raise PD
      and retrospectively investigated the correlation between the ED coil volume rate
      (i.e., volume ratio of all placed coils) and PD in patients treated with
      endosaccular embolization using this coil. Methods: Excluding aneurysms treated
      with a stent, 292 aneurysms treated using ED coils were included in this study.
      The 292 aneurysms and aneurysms with >=30%, >=40%, and >=50% ED coil volume rates
      (202, 168, and 129 aneurysms, respectively) underwent linear regression analysis
      of the following seven factors' influence on PD:ED ratio, aneurysm volume, neck
      width, height, maximum diameter, dome-to-neck ratio, and aspect ratio. Results:
      Independent factors of a high PD were high ED ratio and small neck width on
      analyses of aneurysms with an ED ratio of >=40% and >=50%. Only neck width was an
      independent factor on analyses of all 292 aneurysms and aneurysms with ED ratio
      of >=30%. Conclusion: The use of ED coils in high volume rate correlated with a
      high PD and may contribute to prevent recanalization in small aneurysms.

PMID- 30283515
TI  - Gravity-guided Stereotactic Brain Biopsy.
AB  - Introduction: This study describes a technique using gravity for guidance in
      stereotactic brain biopsy. This will be especially useful in hospitals where the
      stereotactic equipment is unavailable. Objectives: The aim of this study is to
      describe the technique, develop a formula to define its limits of accuracy, and
      report on its clinical application. Methods: Using the positioning laser grid
      lines on the computed tomography scanner, a small metallic marker is placed on
      the scalp at the intended biopsy site. The distance between the tumor and the
      inner table of the bone is measured. In the operating theater, the patient is
      positioned such that the tip and the bridge of the nose are aligned in a
      horizontal position. The patient's two eyebrows or the orbital canthi are aligned
      in a vertical line. Simultaneously, the posterior borders of the two pinnae are
      aligned vertically. Gravity is used to guide the biopsy needle through the marked
      burr hole into the target. Seven patients had biopsies. One was for targeting the
      craniopharyngioma cyst to place an Ommaya catheter. The fraction of error or
      error fraction (EF), was developed for verification of its limits of accuracy.
      Results: All the biopsies were diagnostic and the Ommaya catheter was correctly
      sited. The EFs at alpha = 5 degrees  were all predictive of the limits of
      accuracy of this technique. Conclusion: This is the first reported gravity-guided
      stereotactic brain surgery. The outcome in all the eight cases showed that it was
      within the limits of its accuracy. EF can be calculated to ensure accuracy. This
      technique is helpful if a commercial stereotactic system is not available.

PMID- 30283516
TI  - Magnetic Resonance Imaging and Neuropsychological Correlates of Subcortical
      Vascular Dementia.
AB  - : Common understanding of dementia is mostly based on the Alzheimer's disease
      model. However, in subcortical vascular dementia (SVaD), several other cognitive
      and behavioral dysfunctions predominate over what is commonly noticed in
      Alzheimer's disease. There are inconsistencies in literature regarding the
      profile of cognitive impairments in vascular dementia. Objective: In the current
      study, different cognitive functions pertaining to different lobes of the brain
      along with neuropsychiatric symptoms we explored in a holistic manner. Materials
      and Methods: A sample of 12 patients diagnosed with SVaD without any comorbidity
      were recruited for the study. All the patients underwent magnetic resonance
      imaging (MRI) scanning and different standardized neuropsychological tests were
      administered. Results: Patients reported various neuropsychiatric symptoms with
      varied severity, mostly falling in moderate range, reflecting organic personality
      change. Most of the cognitive functions pertaining to different lobes of the
      brain were impaired with parietal lobe being intact mostly. Comparison of MRI
      findings and neuropsychological findings revealed that there is involvement of
      cortical functions with the impairment in subcortical structure. Conclusion:
      These findings emphasis need to look beyond clinical diagnosis and MRI findings
      for better rehabilitation of the patients by including cognitive dysfunction as
      well as emotional disturbances prominent in SVaD which might me quite distressing
      for caretakers.

PMID- 30283517
TI  - Prehospital Care in Traumatic Brain Injury: Factors Affecting Patient's Outcome.
AB  - Background: Traumatic brain injury (TBI) is the leading cause of deaths
      worldwide. The morbidity and mortality due to TBI are related to both primary as
      well as secondary insults. The patients who survive from the primary insults,
      some may still have long-term disabilities. Most of these outcomes are related to
      the high incidence of prehospital secondary brain insults. Knowledge of these
      variables and timely management of the disease at the prehospital level can
      significantly improve the outcome and decrease the mortality. Aims: The present
      study is aimed to evaluate the current status of prehospital care, prehospital
      factors, epidemiological characteristics, and outcome of TBI patients at a Level
      1 trauma center. Material and Methods: It is a prospective observational study of
      830 cases of TBI, done from November 15, 2015, to March 15, 2016, in the
      Department of Neurosurgery, Institute of Traumatology, SMS Medical College,
      Jaipur, Rajasthan, India. Results: Analysis of data revealed that the incidence
      of TBI in males is four times higher than females. Most patients are in the age
      group of 21-30 years (30.24%) followed by 31-40 years (18.55%). Road traffic
      injury (69.52%) is the most common mode of injury in the age group of 21-30 years
      followed by injury due to fall (22.77%) which mostly affects the age group of 0
      10 years (72.64%) and 61-70 years (38.6%). Analysis of different factors revealed
      that age is significantly correlated with the outcome having P = 0.016. Glasgow
      Coma Scale, saturation of peripheral oxygen, systolic blood pressure at admission
      are also significantly correlated with the outcome having P < 0.001, P < 0.001,
      and P < 0.001, respectively. Conclusion: It is evident from the study that the
      factors which affect the outcome of a TBI are influenced by prehospital care, and
      thus prehospital management of the TBIs can definitely improve the outcomes.

PMID- 30283518
TI  - Radical Resection of Craniopharyngioma: Discussions Based on Long-term Clinical
      Course and Histopathology of the Dissection Plane.
AB  - Objective: Craniopharyngioma is a benign tumor. However, sometimes, this tumor
      may recur repeatedly even after apparent total resection. This study investigated
      the requirements for ideal radical treatment, based on a discussion of the long
      term clinical course and pathological findings in surgical patients. Methods: We
      performed 81 surgical procedures for 67 patients with craniopharyngioma between
      February 1990 and December 2015. We classified patients into Groups I-III
      according to emphasis of surgery in chronological order, so we investigated the
      tumor recurrence rate and the necessity for postoperative hormonal replacement.
      Results: Multiple comparison of results from the three groups found significant
      differences in recurrence rate between Groups I and II (P = 0.0111) and Groups I
      and III (P = 0.0056). Although there were no differences in recurrence rate
      between Groups II and III, mortality rate of Group III was lower than that of
      Group II. No significant difference was seen between any group in terms of
      hormonal replacement. Conclusions: These results strongly suggest that the
      radical resection used to treat patients in Group III should be given priority as
      the procedure for removing craniopharyngioma.

PMID- 30283519
TI  - Efficacy of Amantadine in Improving Cognitive Dysfunction in Adults with Severe
      Traumatic Brain Injury in Indian Population: A Pilot Study.
AB  - Background: Severe traumatic brain injury (TBI) is associated with disabling
      cognitive impairment. Currently available options to improve the cognitive
      function have been futile. However, recently, commonly used medicine for
      Parkinson's disease, amantadine, has been shown to assist in the improvement of
      cognitive function. Methodology: We conducted a single institution-based
      observational study in adult Indian population. Fifty consecutive patients with
      documented static or declining cognitive function at 2 months of severe TBI
      fulfilling the inclusion/exclusion criteria received amantadine 200 mg/day (100
      mg twice a day) orally or through enteral feeding tube for the duration of 4
      weeks. The functional assessment done with Full Outline of Unresponsiveness
      (FOUR) score, Disability Rating Scale (DRS), and Glasgow Outcome Scale (GOS)
      during 4 weeks of treatment and 2 weeks posttreatment was assessed. Results: The
      cognitive function improved progressively during the 4-week treatment interval as
      shown by significant improvement on FOUR score, DRS, and GOS. However, after
      discontinuation of the drug, the speed of recovery slowed down significantly, but
      the achieved recovery was not lost. Out of fifty, eight patients had convulsions
      as an adverse effect of amantadine, of which five patients required
      discontinuation of the drug with treatment for convulsions. Conclusions: This
      study indicates the safety and efficacy of amantadine in partial reversal of
      cognitive dysfunction in adults with severe TBI in adult Indian population.

PMID- 30283520
TI  - Far-lateral Transcondylar Approach to Anterior Foramen Magnum Lesions - Our
      Experience.
AB  - Background: Initial surgical management of the anterior foramen magnum lesions
      through the posterior approaches was fraught with unacceptable morbidity,
      mortality, and incomplete removal. The far-lateral approach provides excellent
      exposure and access to these lesions resulting in complete excision of these
      lesions with reduced frequency of unwanted complications. Materials and Methods:
      Eight patients with lesions anterior to the brainstem and upper cervical cord
      were surgically treated using the far-lateral transcondylar approach. Two of
      these patients had a meningioma while three patients had "white epidermoid." One
      patient had a vertebral artery (VA) aneurysm while another was a rare case of
      lower brainstem compression by the VA and the last was a clival chordoma. The
      technical aspects of this surgical procedure are briefly illustrated in this
      article. Results: Total excision was achieved in five neoplastic cases while
      subtotal excision was done in one case. The VA aneurysm was satisfactorily
      clipped while in the brainstem compression patient, microvascular decompression
      was done. The VA aneurysm patient developed postoperative lower cranial nerve
      palsies. There were no fresh postoperative deficits in any of the other patients.
      One patient had an unexplained sudden cardiorespiratory arrest 18 h after the
      surgery and succumbed. One patient had cerebrospinal fluid (CSF) otorrhea which
      was satisfactorily managed by intrathecal CSF drainage. Conclusion: The far
      lateral transcondylar approach provides excellent approach to lesions located
      anterior to the brainstem and upper cervical cord. Total excision of these benign
      lesions is safely possible through this approach.

PMID- 30283522
TI  - What do You Expect from Patients with Severe Head Trauma?
AB  - Background: Head trauma is one of the most common mortality and morbidity causes
      in adolescent. Numerous studies have been conducted on changes in laboratory
      results and mortality and morbidity prognostic factors; however, the obtained
      results have been varied and controversial. The aim of this study is to evaluate
      changes in laboratory findings and arterial blood gas (ABG) analyses test at
      admission and investigation of the relation between these changes with outcomes
      in patients with traumatic brain injury. Materials and Methods: In this study,
      laboratory and metabolic variables were compared in patients with severe brain
      trauma and normal subjects. Laboratory and metabolic variables and ABG were
      measured on admission in patients with severe brain trauma and then compared with
      normal values. At last, the correlation between these variables with the
      prognosis in the patients was studied. Results: Of 93 studied patients, 82 were
      male and 11 were female with the mean age of 30.54 years. Among the studied
      variables, prothrombin time (PT), partial thromboplastin time, international
      normalized ratio (INR), creatinine (Cr), blood sugar, sodium (Na+), potassium,
      white blood cell, and blood urea nitrogen increased while hemoglobin and platelet
      decreased significantly. Regarding the ABG results, the difference in PaCO2,
      HCO3, and SO2 at values was significant; whereas there were no statistical
      significant difference between the discharged and expired patients. In contrast,
      PT, INR, Cr, and Na had significant difference comparing the discharged and
      expired patients. Conclusion: Laboratory variables do change in patients with
      severe brain trauma; these changes are influential on patient prognosis,
      especially in case of PT, INR, Cr, and Na.

PMID- 30283521
TI  - Riluzole Can Improve Sensory and Motor Function in Patients with Acute Spinal
      Cord Injury.
AB  - Background: Spinal cord injury (SCI) causes sensory, motor function and consists
      of a large proportion of patients that referred to trauma centers. Riluzole
      blocks the sodium channels and has possible supportive effects on the central
      nervous system. The aim of this study was to investigate the effect of riluzole
      on sensory and motor improvement and pain level in patients with acute SCI.
      Materials and Methods: In this clinical trial, sixty patients with acute SCI with
      A to C Frankel grade selected and randomly divided into two groups (each group
      included thirty patients). The two groups carefully matched in terms of age, sex,
      and Frankel class. Case group, in addition to conventional treatment, received
      riluzole and was evaluated after 6-week, 3-month, and 6-month periods in terms of
      sensory and motor status and compared with control group. Results: There were
      sixty patients divided into case and control groups. In the 6-week follow-up
      period and 3-month follow-up period, there was no significant difference between
      the two groups based on sensory and motor function (P = 0.053). In 6-month follow
      up period, the difference was significant in case group (P = 0.001). Conclusion:
      The compressions between two groups demonstrated a significant difference in
      sensory and motor improvement and reduce pain level in patients with SCI.

PMID- 30283523
TI  - Effect of Local N-acetyl-cysteine in the Prevention of Epidural Fibrosis in Rat
      Laminectomy Model.
AB  - Background: Epidural fibrosis is a major contributing factor to the onset of
      failed back syndrome. Many studies have attempted to prevent this physiological
      response. Interestingly, N-acetyl-cysteine (NAC) has been effective in some cases
      in the treatment of pulmonary fibrosis. Objective: The objective of this study
      was to determine whether local NAC is an effective way to prevent epidural
      fibrosis after laminectomy in rats. Materials and Methods: Twenty Wistar rats
      were used in this study. Animals were divided into two groups: NAC group and a
      control group. We performed two-level laminectomy (L4-L5) in these rats. Rats in
      the control group just had laminectomy, and in the other group, L4 and L5
      laminectomy followed by local treatment with NAC. Four weeks later, the rats were
      killed, and the laminectomy level was subjected to histopathological examination
      to evaluate epidural fibrosis and fibroblast density. Results: Histopathological
      examination showed that after 4 weeks of surgery the NAC group had significantly
      less epidural fibrosis and fibroblasts compared with control group. Conclusion:
      Our findings indicate that NAC decreased spinal epidural fibrosis after
      laminectomy in rats.

PMID- 30283524
TI  - Aneurysmal Subarachnoid Hemorrhage: Geography has a Role.
AB  - Background: The incidence of aneurysmal subarachnoid hemorrhage (SAH) reported in
      the literature has been very variable. Many authors have proposed a geographical
      variation in incidence, but others have dismissed this as being due to
      insufficient pickup rate. In India also, these arguments abound. Our aim was to
      find out if geographical variations exist in the incidence of aneurysmal SAH and
      whether the incidence of aneurysmal SAH was truly less in India as compared to
      the literature. Materials and Methods: The data from 182 consecutive cases of SAH
      admitted to this institution between March 1999 and July 2003 were used for this
      study. Results: There were 84 females and 98 males in this study. More than half
      of the patients were hypertensive. Four-vessel angiogram was done in 113
      patients, of whom sixty-nine were normal. Of the patients with hypertension, 92%
      had angiogram done and was normal in 65% of cases. Conclusions: This study from a
      large general hospital in South India shows that the incidence of aneurysmal
      rupture as a cause of SAH is much less in India and probably in the Indian
      subcontinent in comparison with the western literature thus demonstrating
      geographical variations in the incidence of aneurysmal SAH. It is concluded that
      aneurysms as a cause of SAH are still less in India and that we are not missing
      anything. This study is intended to help target scarce, expensive resources
      toward more common pathologies.

PMID- 30283525
TI  - Microsurgical Anatomy of Medial Temporal Lobe in North-West Indian Population:
      Cadaveric Brain Dissection.
AB  - Aim: The medial temporal lobe (MTL) is a highly complex neuroanatomical structure
      of tremendous neurosurgical importance. It is a common site for epilepsy,
      vascular lesions, and tumors. Owing to the critical location behind the sphenoid
      wing, it is more prone for traumatic contusion often with surgical implications.
      Hence, its microneurosurgical anatomy needs to be evaluated in detail. Materials
      and Methods: Twelve formalin-fixed human cadaveric brains from North-west Indian
      population were dissected under neurosurgical microscope and various dimensions
      of the MTL and their distance from important neurovascular structures were
      measured. Results: The MTL consists of important neural structures such as
      parahippocampal gyrus, uncus, hippocampus, temporal horn, and choroidal fissure.
      The average distance of tentorium from the uncus was 1.96 mm. The temporal horn
      and the inferior choroidal point were located from the anterior temporal pole at
      22.9 mm and 30.9 mm, respectively. Important vessels that are intimately related
      to the MTL were anterior choroidal artery (AchA), posterior communicating artery,
      the P1 segment of posterior cerebral artery, and the M1 segment of middle
      cerebral artery. Conclusion: Complex anatomic and cytostructural organization
      makes the MTL unique. In this study, along with the descriptive anatomy,
      morphometric measurements of various structures were performed. The uncus and its
      relation to other neurovascular structures is well described in literature, but
      its exact distance from them as determined in this study is particularly helpful
      in guiding the surgeons while approaching in this area. Knowledge of the distance
      of the temporal horn from various surfaces is important while opening the
      temporal horn to avoid unnecessary damage to nearby structures.

PMID- 30283526
TI  - Pediatric Extradural Hematoma: Clinical Assessment Using King's Outcome Scale for
      Childhood Head Injury.
AB  - Introduction: Epidural hematoma (EDH) is a traumatic accumulation of blood
      between the inner table of the skull and the stripped off dural membrane and
      predominantly consists of venous blood in infants. The study aims to assess the
      outcome of pediatric EDH using King's Outcome Scale for Childhood Head Injury
      (KOSCHI). Materials and Methods: A total of 72 patients' files were reviewed
      retrospectively with a diagnosis of EDH from January 2012 to December 2014.
      Predesigned proforma was filled using data from patient records. In addition,
      KOSCHI was calculated using recent telephone interviews. Results: Among 72
      patients, 65.3% were male and 34.7% were female. Overall, road traffic accident
      was the most common cause (52.8%) followed by fall, assault, and sports injury.
      The most common symptom was more than two episodes of vomiting which was present
      in 51.4% of patients followed by loss of consciousness in 37.5%, ENT bleed in
      33.3%, headache in 16.7%, and fits in 11.1% of patients. The median follow-up of
      our patients was 19 (6-40) months. Most of our patients made good recovery with
      76.4% of our patients scoring 5b on KOSCHI. Conclusion: EDH is not uncommon among
      children with head injury. It should be suspected in every child with
      posttraumatic skull fracture or scalp hematoma. Prompt surgical intervention can
      give good long-term outcome.

PMID- 30283527
TI  - Serum Magnesium as a Marker of Neurological Outcome in Severe Traumatic Brain
      Injury Patients.
AB  - : Hypomagnesemia is postulated as one of the important determinants of outcome
      following traumatic brain injury (TBI) through its effect on secondary injuries
      to neurons. Aims and Objective: The aim of this study was to determine the
      relationship between serum magnesium level and neurological outcome in patients
      admitted with severe head injury. Materials and Methods: In this prospective
      study, patients admitted with severe TBI were recruited and dichotomized into low
      serum magnesium group and normal serum magnesium group based on the initial serum
      magnesium level. Data were collected regarding age, sex, and Glasgow Coma Scale
      at admission. Neurological outcome of the patients in these groups was assessed
      using Glasgow Outcome Scale at 6 months. Results: Seventy-two patients (male =
      50, female = 22) with a mean (+/-standard deviation) age of 42.5 (+/-12.7) years
      were studied. Forty-two (58%) patients had low serum magnesium level (<1.3 mEq/L)
      at admissions. At 6-month follow-up, 81% of patients with poor neurological
      outcome had low serum magnesium as compared to 19% of patients with good outcome
      (P = 0.01). Hypomagnesemia was associated with poor neurological outcome (odds
      ratio = 2.1, P = 0.04, 95% confidence interval = 1.0-8.8) on regression analysis.
      Conclusion: Hypomagnesemia appears to be an independent prognostic marker in
      patients with severe TBI.

PMID- 30283528
TI  - Morphometric Study of Basilar Artery in the Eastern Indian Population.
AB  - Introduction: The basilar artery (BA) is formed by the fusion of right and left
      vertebral arteries and divides to form right and left posterior cerebral
      arteries. This study was done to provide a baseline database regarding length,
      mid-length diameter, level of origin, and level of termination of BA. Materials
      and Methods: Thirty-eight formalin-fixed brains were obtained from cadavers
      dissected for undergraduate studies. The external length and the average external
      diameter of BA were measured by a digital Vernier caliper. Variation in origin
      and termination of BA was noted using magnifying glass. Results: The length and
      diameter of the BA were 25.58 +/- 3.57 mm and 3.05 +/- 0.41 mm, respectively. The
      origin and termination of BA was normal in most cases. In two cases, the origin
      was above the pontomedullary junction, and in one case, it was below. In two
      cases, the termination was above the pontomesencephalic junction, and in one
      case, it was below. Conclusion: There was no gender predisposition in length and
      diameter of the basilar artery. The baseline data established in this study
      regarding length, diameter, level of origin and level of termination of basilar
      artery will help neurosurgeons and interventional radiologists to diagnose as
      well as plan and execute various vascular procedures such as shunting for the
      treatment of aneurysms and stenosis in the blood vessels of the posterior cranial
      fossa.

PMID- 30283529
TI  - Osteoporosis Presenting as Low Backache: An Entity not Uncommon to be Missed.
AB  - Introduction: Low backache (LBA) is highly prevalent in osteoporotic patients and
      affects their quality of life. Overall, osteoporosis incidence is greater in
      females than in males, and osteoporotic fractures typically occur with only
      modest or moderate trauma. Aims and Objectives: To evaluate osteoporosis as a
      cause of LBA in patients attending a neurosurgical outpatient department and to
      study various risk factors associated with it. Materials and Methods: The study
      entitled "Osteoporosis presenting as LBA: An entity not uncommon to be missed"
      was a 2-year hospital-based study conducted from August 2014 to July 2016 in a
      prospective manner and included 100 patients of osteoporosis with LBA. Analysis
      of records included their chief complaints, signs and symptoms, diagnostic
      investigations performed, treatment modalities they underwent, and further
      recommended management carried on them. Results: Out of total 100 patients
      evaluated, 33 (33%) were male and 67 (67%) were female; the age of patients was
      in the range of 35-70 years (mean 56.54 +/- 91). The number of patients with a
      significant medical or surgical history was 31 (31%). The history of drug intake
      such as thyroxine, steroids, and antiepileptics was present in a total of 11
      patients out of which 10 were female and one was male. Regarding lifestyle
      characteristics of studied patients, a total number of 72 (72%) were having
      sedentary habits with 15 (45.5%) males and 57 (85.1) females, the total number of
      moderate workers was 19 (27.3) males and 10 (14.9%) females, and heavy workers
      were 9 (9%) with 9 (27.3) males and 0 (0%) female. Conclusion: LBA is highly
      prevalent in osteoporotic patients especially in women. The incidence of
      osteoporosis and LBA increased with low body mass index, increasing age, and
      duration of menopause. The various risk factors for osteoporosis include smoking,
      history of medical diseases such as diabetes mellitus, history of hysterectomy,
      and history of antiepileptic, thyroxine, and steroid intake.

PMID- 30283530
TI  - The Benefits of Decision Tree to Predict Survival in Patients with Glioblastoma
      Multiforme with the Use of Clinical and Imaging Features.
AB  - Background: Machine learning is a type of artificial intelligence which aims to
      improve machine with the ability of extracting knowledge from the environment.
      Glioblastoma multiforme (GBM) is one of the most common and aggressive primary
      malignant brain tumors in adults. Due to a low rate of survival in patients with
      these tumors, machine learning can help physicians for better decision-making.
      The aim of this paper is to develop a machine learning model for predicting the
      survival rate of patients with GBM based on clinical features and magnetic
      resonance imaging (MRI). Materials and Methods: The present investigation is an
      observational study conducted to predict the survival rate in patients with GBM
      in 12 months. Fifty-five patients who were registered in five Iranian Hospitals
      (Tehran) during 2012-2014 were selected in this study. Results: This study used
      Cox and C5.0 decision tree models based on clinical features and combined them
      with MRI. Accuracy, sensitivity, and specification parameters used to evaluate
      the models. The result of Cox and C5.0 for clinical feature was <32.73%, 22.5%,
      45.83%>, <72.73%, 67.74%, 79.19%>, respectively; also, the result of Cox and C5.0
      for both features was <60%, 48.58%, 75%>, <90.91%, 96.77%, 88.33%>, respectively.
      Conclusion: Using C5.0 decision tree model in both survival models including
      clinical features, both the imaging features and the clinical features as the
      covariates, shows additional predictive values and better results. The tumor
      width and Karnofsky performance status scores were determined as the most
      important parameters in the survival prediction of these types of patients.

PMID- 30283531
TI  - Management of Postoperative Discitis: A Review of 31 Patients.
AB  - Background: The aim of the study was to retrospectively evaluate the outcome of
      medical management of postoperative discitis (POD). Materials and Methods: A
      total of 31 patients treated for POD were included in the study. Clinical,
      radiological, and laboratory data of all patients were collected and evaluated.
      All patients were treated initially with bed rest and antibiotic therapy after
      radiological diagnosis. Surgical management was undertaken after failure of 4
      weeks of conservative management. All cases were followed clinically with
      laboratory and radiological investigations. Results: Five cases failed to respond
      to medical management and were treated surgically with debridement and
      transpedicular fixation. All patients showed clinical recovery till the last
      follow-up. Conclusion: Early diagnosis and proper management are the keys to
      successful outcome of postoperative spndylodiscitis. Surgical debridement and
      fusion are required when conservative treatment fails.

PMID- 30283532
TI  - Study of Incidence and Factors: Risk and Preventive, of Chronic Subdural
      Hematoma/hygroma in Clipped Patients of Unruptured Intracranial Aneurysms - An
      Institutional Experience.
AB  - Introduction: One of the underreported complications of clipping of unruptured
      aneurysm is chronic subdural hematoma/hygroma (CSDH). It can cause sudden
      deterioration and might need emergency evacuation. Recently, very few papers have
      studied its incidence and predisposing factors. We are reporting our
      institutional experience of it along with the study of its risk factors and
      possible pathogenesis. Methodology: Totally 91 postoperative patients of
      unruptured aneurysms were retrospectively analyzed. Totally 21 patients had CSDH
      who were operated. In rest seventy patients, there was no CSDH. Results: Male
      sex, old age, anticoagulant use, presence of pneumocephalus and dead space were
      significantly associated with occurrence of CSDH, whereas arachnoidoplasty
      significantly protected against it. There was no significant relation of CSDH
      with Gorei-san use. Conclusions: We recommend arachnoidoplasty should be carried
      out in all patients of clipping of unruptured aneurysm. Male patients or/and
      patients with dead space with pneumocephalus must be given extra attention like
      avoiding any dead space in postoperative period, doing arachnoidoplasty and
      regular follow up till 1st year.

PMID- 30283534
TI  - Favorable Outcome of Endovascular Treatment for Intracranial Aneurysms: A Single
      Center Study in Thailand.
AB  - Purpose: The purpose of this study is to collect the information on patients with
      intracranial aneurysm (IA) receiving endovascular management in Siriraj Hospital,
      Mahidol University, Thailand. Materials and Methods: We retrospectively reviewed
      data from patients with IA who underwent endovascular treatment from January 1997
      through July 2013. We collected patients' demographic data including age, sex,
      clinical presentations, and aneurysmal profiles, as well as endovascular
      treatment technique, complications, angiographic results, and regrowth rate.
      Treatment results included success rate, clinical findings during follow-up, and
      regrowth rate. Results: We reviewed data from 497 patients with 636 aneurysms
      (female:male ratio, 1.9:1; age range, 15-90 years; mean age, 59.18 years) and 69%
      presented with rupture. One hundred and twenty patients with 127 aneurysms
      received endovascular treatment. The most common location for endovascular
      treatment was the posterior communicating artery (15.8%), and endovascular
      techniques were used most often for posterior circulation and paraclinoid
      aneurysms. The success rate was approximately 99.2% with a 16.5% regrowth rate
      and no rebleeding. Regrowth rate did not correlate with immediate postoperative
      angiographic findings. We encountered 23 complications (18.1%); most commonly,
      intra-procedural rupture (7/23). Good outcomes occurred in approximately 95.9% of
      the patients. Conclusions: The success rate for endovascular treatment was >90%.
      Regrowth rate and clinical outcomes were within standard limits. Posterior
      circulation and paraclinoid aneurysms were our main targets. We tended to use
      fewer devices and simpler techniques to secure ruptured IA; however, the regrowth
      rate was similar to that using device-assisted techniques in other studies. We
      found no significant factors affecting regrowth rate, including immediate
      posttreatment angiographic results.

PMID- 30283533
TI  - Morbidity Audit of 704 Traumatic Brain Injury Cases in a Dedicated South Indian
      Trauma Center.
AB  - Background: In the era of evidence-based health care, protocol of intervention in
      traumatic brain injury (TBI) cases help decide more easily and safely about
      patients and prevent unnecessary transfer of patients to other centers.
      Objectives: The objective of this study is to provide protocol-based intervention
      and evaluate the epidemiological, clinical characteristics of TBI cases. Methods:
      This prospective study was conducted on 704 patients who were suspected of TBI at
      the Department of Neurosurgery, Narayana Medical College and Hospital, followed
      by protocol-based intervention assessed and reassessed repeatedly. Results:
      Overall, TBI involved 569 (80.82%) adults in the productive age groups (21-60
      years); among males 81.47%. Among males, highest (23.15%) cases were in the age
      group of 31-40 years while in females, majority (27.04%) was among 41-50 years.
      Road traffic accidents were the most common (54.12%) mechanism of injury followed
      by fall (21.31%) and two-wheelers (15.20%). More than half sustained mild TBI
      (51.42%) while 26.28% moderate TBI and 22.30% severe TBI; among males, severe TBI
      victims 102 (18.82%) were in the productive age group. Loss of consciousness was
      almost a universal and significant observation (95.45%); vomiting was next common
      finding (76.42%). Bleeding from the ear-nose-throat (ENT) region was more in
      males (33.58%) than females (20.75%). Glasgow coma scale was significantly
      related with loss of consciousness (91.08%), vomiting (63.06%), and ENT bleeding
      (44.59%) in severe, moderate, and mild injuries. Conclusion: A rational clinical
      acumen with judicious use of diagnostic protocol leads to better management of
      TBI without unnecessary imaging and thus reduce total health-care costs.

PMID- 30283535
TI  - Factors Affecting Functional Outcome after Decompressive Craniectomy Performed
      for Traumatic Brain Injury: A Retrospective, Cross-sectional Study.
AB  - Background: Factors affecting functional outcome after decompressive craniectomy
      (DC) performed for traumatic brain injury (TBI) remain poorly understood.
      Methods: We conducted a retrospective study of all patients who underwent primary
      DC for TBI at our hospital between 2010 and 2014. Multivariate regression
      analyses were used to determine the predictors of functional outcome and overall
      survival. Results: A total of 98 patients with severe (n = 81, 82.6%) or moderate
      (n = 17, 17.4%) TBI underwent primary DC and were included in this study. The 30
      day and overall mortality rates were 15.3% and 25.5%, respectively. At a median
      follow-up of 90 (interquartile range (IQR): 38-180) days, median Karnofsky
      Performance Status (KPS) and Glasgow outcome scale-extended (GOSE) scores were 50
      (IQR: 20-70) and 5 (IQR: 3-7), respectively. Young age and severe TBI were
      predictors of mortality. Glasgow coma scale (GCS) score on discharge was a strong
      predictor of KPS and GOSE scores. Conclusion: Primary DC afforded an acceptable
      functional outcome (GOSE score >=5) in 45.9% of patients. Young age and lower GCS
      at presentation were associated with worse survival. GCS score on discharge was a
      strong predictor of functional outcome.

PMID- 30283536
TI  - Prognosis of Hormonal Deficits in Empty Sella Syndrome Using Neuroimaging.
AB  - Aim: We have evaluated the anatomic measurements on sellar area of patients who
      were radiologically diagnosed with empty sella to determine the relation between
      the amount of pressure on the adenohypophysis and hormonal imbalances. Materials
      and Methods: Sixty-one cases were diagnosed with empty sella and had hormone
      tests and hypophysis magnetic resonance (MR). The cases were categorized into two
      groups - patients with hypophyseal hormone anomaly and patients without hormone
      anomaly. We have measured interclinoid distance, anteroposterior distance from
      the anterior diaphragm sella to the pituitary stalk, depth of the sella turcica,
      craniocaudal distance of the optic chiasm from the diaphragm sella, the heights
      of the right and left adenohypophysis, subcutaneous fat thickness measured
      orthogonal to the coronal suture and posteriorly at the level of C2-C3 for two
      groups on hypophysis and cranial MR imaging MRI. Results: Twenty-five hormone
      positive cases (40.9%) (hormone test were abnormal) and 36 hormone-negative cases
      (59.1%) (hormone tests were normal) were included in the study. The most common
      hormone abnormality was thyroid-stimulating hormone, T3 and T4 deficiency in 12
      cases (48%) and increase in prolactin level in 7 cases (28%). Right
      adenohypophysis height was 1.54 +/- 0.840 mm for the 1st group, and 1.96 +/- 0.83
      mm for the 2nd group. The left adenohypophysis height was 1.66 +/- 0.80 mm for
      the 1st group, and 1.94 +/- 0.94 mm for the 2nd group. It was found out that the
      thickness at right and left side in the hormone-positive group diminished
      significantly. Conclusion: Adenohypophysis height and distance between stalk and
      optic nerve were good determiner for hormone defect.

PMID- 30283537
TI  - Nonmissile Anterior Skull-Base Penetrating Brain Injury: Experience with 22
      Patients.
AB  - Background: Nonmissile anterior skull-base penetrating brain injuries (NASBPBIs)
      have specific characteristic features that are different from missile injuries.
      Our study presents our experiences on the characteristic features as well as
      management of NASBPBI. Materials and Methods: We retrospectively reviewed 22
      consecutive patients with NASBPBI managed at our institute during a 13-year
      period. The mechanism of injury, clinical investigations, and complications were
      analyzed, with more emphasis on diagnostic and treatment regimen. Results: The 22
      cases included in our study comprise of 20 males and 2 females. Majority (72.7%)
      of the patients were adults with a mean age of 27.5 years. The mechanisms of
      injury often include accidental fall, either onto a small-diameter sharp object
      (10 cases) or while carrying such an object in the hand (4 cases). The other
      common mechanisms were stabbing, accident, or during an altercation (8 cases).
      Clinical manifestations included periorbital hematoma (10 cases, 45.5%) and
      cerebrospinal fluid rhinorrhea or orbitorrhea (4 cases, 18.2%) as well as signs
      of embedded foreign object (8 cases, 36.4%). We performed emergency craniotomy in
      21 cases and skin debridement in one case. Postoperative complications were
      abscess (1 case), epilepsy (1 case), and traumatic carotid-cavernous fistula (1
      case). Conclusion: Nonmissile injuries are generally on the rise and therefore
      deserve more attention. We observed that clinical outcomes were excellent in 14
      (Glasgow Outcome Scale [GOS] score of 5) and good in the remaining 8 patients
      (GOS of 4) during 6-month-10-year (mean 4.6 years) follow-ups.

PMID- 30283538
TI  - The Effectiveness of Dural Venous Sinus Sacrifice as a Treatment of Aggressive
      Type Cranial Dural Arteriovenous Fistulas.
AB  - Objective: To evaluate the effectiveness of dural venous sinus sacrifice as a
      treatment of aggressive type cranial dural arteriovenous fistulas (dAVFs) in
      terms of both clinical outcome and angiographic outcome. Materials and Methods:
      One hundred and twenty-eight patients with 163 aggressive type cranial dAVFs who
      were treated with dural sinus sacrifice were retrospectively reviewed. Clinical
      and angiographic outcomes were analyzed. Procedural complications were also
      recorded. Only 103 patients (80.5%) who had been following up for at least 90
      days were analyzed for clinical outcome. Results: There were 53 males and 75
      females with age ranging from 20 years to 93 years (mean age 55.44 years). The
      overall angiographic cure rate of dural venous sinus sacrifice as a part of the
      treatment of aggressive dAVFs was 81.6%. Considering clinical outcome (average
      duration of follow-up was 2 years and 6 months), 75 patients (72.8%) had clinical
      improvement and 21 (20.4%) were clinically stable. Worsening of the presenting
      symptoms was observed in 7 patients (6.8%). Procedural complications were found
      in 5 patients (3.9%). Conclusion: Dural venous sinus sacrifice is a safe and
      effective treatment strategy with high angiographic cure rate, good clinical
      outcome, and low incidence of procedural-related complication.

PMID- 30283539
TI  - Stab Wounds to the Head; Case Series, Review of Literature, and Proposed
      Management Algorithm.
AB  - Background and Objectives: Stabbing the head is a rare event. It may occur
      following an assault or self-inflicted injury. We intend to report our experience
      with four such cases and review narratively the relevant literature. A treatment
      algorithm will be delivered. Materials and Methods: We have reviewed four of our
      cases; three were stabbed to the orbit and one to the head. Results: Enucleation
      was performed in one case. Vision could be preserved in the other two and brain
      abscess developed in the other cases due to a retained piece of knife. We made a
      comparison between our cases and those limited reports in the literature to reach
      an algorithm. Conclusion: The temporal region and the orbit are the targets
      mostly attacked in the craniofacial stabs. Since knives have a sharp and thin
      edge, they may break when penetrating the skull. The damage to the brain tissue
      and the retained piece of knife may be missed easily by overlooking the small
      injury to the scalp. The suggested algorithm would be a contrast-enhanced
      computed tomography scan of the skull and brain and a kind of brain vascular
      study are necessary, considering the location of the knife in the skull and brain
      passing the area with crowded vasculature. The best treatment protocol is surgery
      accompanied by antibiotic therapy.

PMID- 30283540
TI  - Hemilaminectomy for Spinal Cord Intradural Tumors: An Institutional Experience.
AB  - Introduction: Laminectomy is the workhorse of spinal cord tumor surgery. This
      procedure is not without the debilitating sequelae of postoperative pain and
      delayed kyphosis. Hemilaminectomy is an alternate option to laminectomy which
      offers the advantage of preserving the posterior supporting structures of the
      spine on the contralateral side. In this study, we analyze the outcome of
      hemilaminectomy clinically with improvement in pain scores and Nurick's grade as
      well as radiologically by assessing for the development of delayed kyphosis. We
      also discuss the technique and operative nuances of hemilaminectomy in intradural
      extramedullary tumors of the spinal cord. Materials and Methods: All patients
      with intradural spinal cord tumors were included in the study. All patients
      underwent unilateral hemilaminectomy (UHL) depending on the laterality of the
      tumor on the preoperative magnetic resonance imaging. Preoperative neurologic
      status was assessed with Nurick's grade for tumors involving the cervicothoracic
      region tumors, and visual analog scale scores were recorded for tumors of
      Thoracic, Lumbar and Lumbosacral regions. The postoperative outcomes were
      assessed by improvement in respective scales on follow-up. The occurrence of
      delayed spinal deformity was assessed by follow-up X-rays. Any complications
      whether intraoperative or postoperative were recorded. Results: There were a
      total of 34 cases of intradural extramedullary tumors in this study. Patient
      population consisted of 11 males and 23 females. Total excision was achieved in
      31 patients. In three patients, we were unable to achieve complete removal
      through UHL. In these patients the procedure was converted to total laminectomy.
      They were excluded from analysis. The distribution of the tumors was in cervical,
      cervicothoracic, thoracic, lumbar, and lumbosacral region. All patients presented
      with pain or varying degrees or neurologic deficits. Sixteen patients underwent
      UHL from the right side, while 18 from the left. There were no intraoperative
      complications. The neurological status and pain scores of all patients improved
      postoperatively at 3 and 6 months of follow-up. There was no radiological
      evidence of kyphosis of the involved segment. Conclusion: With a small learning
      curve, UHL is a good corridor for the removal of intradural extramedullary spinal
      cord tumors. This approach offers the advantage of less postoperative pain and no
      postoperative deformity.

PMID- 30283541
TI  - Effect of Mannitol Irrigation on Brain Edema in a Live Rat Model.
AB  - Background: Mannitol has been used intravenously for decreasing cerebral edema
      since decades. The study was performed to evaluate the effect of its irrigation
      on edema in live rats. Edema was induced by artificial brain injury. We hereby
      present our results on the same using live rats and confirm its beneficial effect
      on reducing edema when used as irrigation. Aims: The aim of this study is to
      evaluate the effect of mannitol irrigation in reducing cerebral edema in rat
      brain after induction of artificial trauma and to compare the results with
      standard normal saline irrigation using randomized controlled study. Settings and
      Design: This study was a prospective randomized controlled trial. Materials and
      Methods: A total of 20 fully grown Albino Wistar rats were subjected to
      artificial trauma after a burr hole and divided randomly into two groups of ten
      rats each. One group was subjected to mannitol irrigation after durotomy and the
      other was subjected to normal saline. Tissue biopsy was sent at the end of 1 h to
      check for the status of edema and was classified into three grades. Statistical
      Analysis Used: Comparison of proportions test. Results: Mannitol irrigation
      produced a statistically significant difference (P = 0.022) in the grade of edema
      at the end of 1 h as compared to normal saline. Conclusions: Mannitol irrigation
      can be used during neurosurgical procedures instead of normal saline to reduce
      postoperative brain edema.

PMID- 30283542
TI  - Burr Holes Revascularization in Three Pediatric Cases of Moyamoya Syndrome: Easy
      Choice or Insidious Trap? Case Series and Review.
AB  - Introduction: Moyamoya disease is a steno-occlusive cerebrovascular disease of
      unknown etiology involving the terminal portion of the internal carotid artery
      and the proximal portions of the anterior and middle cerebral arteries with
      associated collateral vascular network. When the vascular pattern is associated
      with a particular condition (e.g., Type 1 neurofibromatosis, Down syndrome), it
      is defined as moyamoya syndrome (MMS) (or quasi-moyamoya). Among different
      indirect bypass techniques used to prevent ischemic injury by increasing
      collateral blood flow to hypoperfused areas of the cortex, multiple burr holes
      technique is an easy and diffuse indirect revascularization approach in the
      treatment of moyamoya. Discussion: While the effectiveness in patients with
      moyamoya disease was demonstrated, its role in MMS remains uncertain. In this
      study, we describe surgical and diagnostic implications in three pediatric cases
      of moyamoya sydrome unsuccessfully treated with multiple cranial burr hole
      technique. A critical review of the literature about the use of the surgical
      indirect revascularization techniques in pediatric patients was also reported.

PMID- 30283544
TI  - Technique of Posterior Clinoidectomy and Its Applications.
AB  - An understanding of the microsurgical anatomy of posterior clinoid process (PCP)
      is extremely important to where the removal of PCP is required to access the
      interpeduncular and prepontine cisterns and upper basilar artery region to manage
      the aneurysms located in this region. In the present article, we describe our
      experience with a technique that is safe and provides ample space to look into
      these regions. The key to safe drilling is that the drilling of the posterior
      clinoid needs to be performed in a "touch and back" manner (rather than clockwise
      or counterclockwise motion) to break the cortex.

PMID- 30283543
TI  - Congenital Absence of Unilateral Internal Carotid Artery with an Intracerebral
      Aneurysm.
AB  - The absence of the internal carotid artery (ICA) is a rare congenital anomaly.
      Diagnosis of this entity is important because of its association with the
      cerebral aneurysm and also indicated during planned carotid or transsphenoidal
      surgery in thromboembolic disease and in the surveillance and detection of
      associated cerebral aneurysms. We report a case of congenital absence of
      unilateral ICA with associated cerebral aneurysm of the anterior cerebral artery.

PMID- 30283545
TI  - Temporary Worsening of Perianeurysmal Edema Following Clipping of a Partially
      Thrombosed Giant Pericallosal Artery Aneurysm.
AB  - We present a case of a partially thrombosed giant aneurysm of the pericallosal
      artery that experienced a temporary worsening of perianeurysmal edema after
      clipping. A 66-year-old man presented with progressive weakness of the right leg.
      Imaging studies revealed a partially thrombosed giant aneurysm at the bifurcation
      of the left pericallosal artery with concomitant perianeurysmal edema. The
      aneurysm was thought responsible for the symptoms of the patient, and he agreed
      to undergo clipping surgery. The aneurysmal neck was clipped using two long
      aneurysm clips without dissecting the aneurysmal dome. The patient woke up from
      anesthesia with the right-sided hemiparesis, which progressed to hemiplegia by 12
      h after surgery. Brain computed tomography revealed worsening of the
      perianeurysmal edema. Fortunately, his symptoms resolved completely by 2 weeks
      after surgery with conservative management. Perianeurysmal edema is frequently
      observed in patients with partially thrombosed giant aneurysms. Although
      worsening of perianeurysmal edema is a relatively common complication of
      endovascular procedures, its occurrence after clipping has rarely been reported.
      The worsening may have been induced by release of inflammatory cytokines from
      aneurysm wall, which was rendered ischemic due to obliteration of the vasa
      vasorum by the clips. Perianeurysmal edema may develop or worsen after clipping
      of a partially thrombosed giant aneurysm if the interface between the aneurysm
      and surrounding brain is not fully dissected.

PMID- 30283546
TI  - Trans-Sellar Trans-Sphenoidal Herniation of Third Ventricle with Cleft Palate and
      Microophthalmia: Report of a Case and Review of Literature.
AB  - Trans -sellar trans-sphenoidal encephalocele is an extremely rare entity. We
      present the case of an 18-month old boy who presented with a trans-sellar, trans
      sphenoidal encephalocele associated with cleft lip, cleft palate and
      microphthalmia. This patient was treated successfully by a trans-cranial extra
      dural route. In this paper, we discuss the clinico-radiological findings as well
      as various surgical options in managing these rare lesions and briefly review the
      literature.

PMID- 30283547
TI  - Hemifacial Spasm Caused by a Vein: A Case Report.
AB  - Hemifacial spasm (HFS) caused by a venous offender is rare, and its clinical
      course and optimal surgical strategy are unclear. A case of 57-year-old male who
      had an HFS caused by a venous offender is described in this report. Frontalis,
      orbicularis oculi, orbicularis oris, and mentalis muscles were involved while his
      platysma muscle showed no spasm. He was treated successfully with microvascular
      decompression using Teflon felt and 12 months outcome was excellent without any
      complications. Lateral spread response was not observed in the facial
      electromyography during the whole operation. Adequate visualization of the facial
      nerve root exit zone and meticulous exploration for offenders are necessary to
      avoid surgical failure and reoperation.

PMID- 30283548
TI  - Occipital Interhemispheric Approach for Surgical Removal of the Middle Third Falx
      Meningioma: Two Case Reports.
AB  - Obtaining adequate working space is difficult for complete and safe resection of
      meningioma located in the middle third of the falx, because of the risk of damage
      to the bridging veins that flow into the superior sagittal sinus and the location
      near the eloquent area. Consequently, surgical resection of the meningioma in the
      middle third of the falx tends to result in neurological disorders caused by
      retraction of the brain and injury of the bridging vein. Two patients underwent
      tumor removal of the falx meningiomas located in the middle third of the falx
      through the occipital interhemispheric approach (OIA) in the lateral semiprone
      position with the affected side down. Tumor resection was achieved safely and
      less invasively. Both patients suffered numbness and motor weakness, but these
      neurological dysfunctions improved and clinical courses were uneventful.
      Postoperative computed tomography showed neither brain swelling nor contusion in
      both cases. The OIA can remove tumor in the middle third of the falx, because the
      approach avoids the bridging veins, and provides working space without excessive
      mechanical cerebral retraction.

PMID- 30283549
TI  - Scedosporium apiospermum: An Emerging Fatal Cause of Fungal Abscess and
      Ventriculitis after Near-drowning.
AB  - Herein, we describe a fatal case of central nervous system (CNS)
      pseudallescheriasis following near-drowning. A 13-year-old boy, who had been
      successfully resuscitated after near-drowning, presented with a transient episode
      of mental confusion during a hospital stay after recovering from severe
      aspiration pneumonia and respiratory failure. A magnetic resonance imaging (MRI)
      scan of the brain showed a small brain abscess in the left basal ganglia and
      ventriculitis in the left lateral ventricle. The brain abscess and ventriculitis
      did not respond to 4 weeks of antibiotic treatment and appeared even worse on a
      follow-up MRI. A diagnosis of CNS pseudallescheriasis was only possible with
      invasive stereotactic biopsy and aspiration of the abscess that showed the
      presence of hyphae and Scedosporium apiospermum. CNS pseudallescheriasis did not
      respond to multiple combinations of antifungal agents, including amphotericin B,
      isoconazole, itraconazole, and voriconazole. Two ventricular drainages and
      insertion of Ommaya reservoirs with intraventricular injection of voriconazole
      were insufficient to halt the infection. The patient passed away from sudden
      septic shock 2 months after identification of the brain abscess and
      ventriculitis. The patient's diagnosis was delayed because multiple examinations
      of the cerebrospinal fluid did not show positive cultures and could only be
      obtained from the aspirates of stereotactic biopsy. Physicians should be aware of
      CNS pseudallescheriasis associated with near-drowning because of the difficulty
      of diagnosis and the high mortality rate (70%) owing to poor responses to
      currently available antifungal agents.

PMID- 30283550
TI  - Oyster Calcification of Infected Bone Flap: A Rare Complication.
AB  - An extremely rare case of chronic epidural empyema after cranioplasty is
      presented. It derives its extreme rareness from its association with
      calcification. This patient when presented to our department had a complaint of
      swelling with on and off discharging sinus for 2 months adjacent to old incision
      scar mark. The patient had a history of decompressive craniectomy and evacuation
      of acute subdural hematoma, in some other institution, 8 years back. Following
      that, the patient underwent cranioplasty with the exteriorized and preserved bone
      flap. In the meantime, he was asymptomatic. It is a unique interesting case of
      chronic epidural empyema with calcified walls after 8 years of long duration
      following cranioplasty.

PMID- 30283551
TI  - Primary Giant Cerebral Hydatid Cyst in an 8-year-old Girl.
AB  - Echinococcosis, also called hydatid disease, is a parasitic disease that passes
      from animals to humans. Literature reports suggest very rare cases of cerebral
      hydatid cysts. Brain involvement with hydatid disease occurs in 1%-2% of all
      Echinococcus infections. In this report, we aim to emphasize the presentation of
      such an isolated primary cerebral hydatid cyst, discuss its radiological
      features, Emergency department management, inpatient medical management, referral
      to neurosurgery, consequent operative procedures, postoperative care, and
      outcome.

PMID- 30283552
TI  - Pyothorax-associated Angiosarcoma Metastasized to the Brain with Multiple and
      Progressively Expanding Hematomas: Case Report and Literature Review.
AB  - The brain metastasis of angiosarcoma is very rare, and little is known about its
      clinical features or therapeutic strategy. A 74-year-old male was hospitalized
      for disturbance of consciousness. Radiological examination revealed multiple
      cerebral hematomas. Gadolinium contrast-enhanced magnetic resonance imaging
      showed no significant enhancement at any of the lesions. To detect a suspected
      metastatic brain tumor or abscess, a full-body scan was performed but revealed
      only a poorly enhanced mass in the removal cavity caused by thoracoplasty in the
      left upper chest. After admission, a cascade of expansion of those hematomas
      occurred in the right frontal, left parietal, and right temporal lobes, and each
      lesion thus had to be sequentially removed by craniotomies. The pathological
      diagnosis of the right frontal lesion was an abscess with hematoma. However, a
      malignant vascular tumor was highly suspected because of many CD31(+)/Ki-67(+)
      cells in the left parietal lesion. A mass in the scar caused by thoracoplasty was
      suspected to be the primary lesion, and brain metastasis of angiosarcoma was
      finally diagnosed. Whole-brain irradiation and systemic paclitaxel administration
      were performed, and a complete response for the brain lesions was obtained for 22
      months; the patient then died of an intratracheal hemorrhage. This case
      represents the first report of multiple brain metastases from pyothorax
      associated angiosarcoma accompanied by sequentially and gradually expanding
      hematomas, as well as the first case with the control of metastatic brain lesions
      for over 1 year after the onset of neurological symptoms. Control of the lesions
      could be achieved by their total removal with complete hemostasis, as well as
      additional radio- and chemotherapy.

PMID- 30283553
TI  - Spontaneous Transformation of Vestibular Schwannoma into Malignant Peripheral
      Nerve Sheath Tumor.
AB  - Although radiosurgery-induced transformation of vestibular schwannoma (VS) into
      malignant peripheral nerve sheath tumor (MPNST) is being widely discussed, little
      attention is paid to the spontaneous transition of these tumors. Although the
      pathogenesis of this phenomenon remains uncertain, growing number of reported
      cases might call to notice them. We present a case of a 29-year-old woman who
      suffered right-sided hearing loss which remained untreated for 4.5 years.
      Magnetic resonance imaging revealed a right cerebellopontine tumor and the
      patient underwent tumor removal through retrosigmoid approach. Pathologically,
      the tumor was benign acoustic schwannoma with increased Ki-67 8%-10%. The tumor
      relapsed only 6 months later and was removed again-this time it was malignant
      peripheral nerve sheath tumor MPNST. The patient was treated with stereotactic
      radiotherapy, but despite that tumor growth was observed again and she underwent
      the third operation. Later on, tumor progression was noted with multiple
      intraaxial metastases and patient died 17 months after the diagnosis of MPNST had
      been confirmed. This is a seventh documented case of spontaneous transformation
      of VS into MPNST, which is clinically important for recording.

PMID- 30283554
TI  - A Rare Case Report of Multiple Intracranial Aneurysms with Factor VII Deficiency.
AB  - Pathogenesis of intracranial aneurysms is multi-factorial. Origin of aneurysm may
      be acquired or genetic, and there may be more than one aneurysm simultaneously,
      or there may be the formation of a new aneurysm after treatment of previous one.
      Collagen vascular disorders, neurofibromatosis, polycystic kidney disease, and so
      many other disorders are associated with multiple intracranial aneurysms. As
      Factor VII deficiency is also genetic in origin, there might be a correlation
      between deficiency of the same with multiple intracranial aneurysms. Only one
      such case is reported in the literature and we are reporting such a rare case
      having a similar association.

PMID- 30283555
TI  - Rupture of Persistent Primitive Trigeminal Artery-basilar Artery Aneurysm Managed
      with Stent-assisted Coiling.
AB  - Persistent primitive trigeminal artery (PPTA), a fetal carotid-basilar
      anastomosis, is the most common embryological vascular remnant persisting into
      adult age. However, reported cases associated with cerebral aneurysms are rare. A
      33-year-old female presented with an extremely rare PPTA-basilar artery (PPTA-BA)
      aneurysm manifesting as subarachnoid hemorrhage. Computed tomography revealed
      subarachnoid bleeding in the prepontine cistern, and cerebral angiography
      disclosed a PPTA-BA aneurysm. The aneurysm was managed with stent-assisted
      coiling technique to achieve complete obliteration. The patient was discharged
      without neurological deficits 2 weeks later. At 6 months follow-up, the patient
      is doing well and has returned to her previous daily activities. PPTA-BA
      aneurysms usually present with cranial nerve palsy and sometimes with carotid
      cavernous fistulae if they rupture. Their deep seating favors interventional
      management as a first option and this case illustrates the efficacy and safety of
      endovascular treatment. This case adds to the evidence that endovascular
      techniques are a safe and effective tool in managing aneurysms of the primitive
      trigeminal artery. Even in cases where the anastomosis itself is not preserved,
      the patient can be managed satisfactorily, provided that the patency of the
      basilar and the carotid artery are kept, like in our patient.

PMID- 30283556
TI  - Congenital Skull Anomaly with Multiple Brain Stones and Symptomatic Meningioma of
      Medial Sphenoid Wing.
AB  - Intracranial calcifications are not uncommon and are mostly seen with
      intracerebral hematomas, tuberculomas, and brain tumors. These lesions may be
      intra- or extra-axial and occasionally pose challenge in the diagnosis. We report
      a case of multiple intracranial extra-axial calcifications with congenital skull
      anomaly and multiple meningiomas. Authors could not find similar case reported in
      the literature and present their findings and discuss relevant literature.

PMID- 30283557
TI  - Malignant Conversion to Glioblastoma in Neurofibromatosis Type I-associated
      Pleomorphic Xanthoastrocytoma: Unknown Predictors of Favorable Outcome.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a benign glial tumor, the association of
      which with neurofibromatosis type I (NF-1) has been often reported in the
      literature. Although malignant conversion to glioblastoma may be seen in 5%-10%
      of PXA, the same has been reported only once in the presence of NF-1. We report,
      so far known to be only the second such case all over. A 25-year-old male, a
      known case of NF-1, underwent frontal craniotomy for a superficially located
      right frontal lesion, histology of which suggested PXA. Two years later, the
      lesion recurred and the subsequent surgery revealed malignant conversion to
      glioblastoma. After adjuvant radiotherapy, the patient now continues to do well
      and is free of disease after another 3 years of follow-up. We believe that if low
      levels of neurofibromin are seen in such cases with malignant conversion,
      subsequently increased neurofibromin levels may be responsible for better overall
      survival in these patients.

PMID- 30283558
TI  - Multiple Extraneural Metastases of Anaplastic Oligodendroglioma.
AB  - Oligodendrogliomas (ODGs) is a diffuse glial tumor that constitutes 4.2% of all
      brain tumors. Extraneural metastases, sometimes seen in glioblastoma multiforme,
      are extremely rare in ODG. In this report, we present a 63-year-old male patient
      who was diagnosed with Grade 3 ODG and had an intracranial mass resected in our
      clinic 4 years ago. The subject now presented with low back pain and was found to
      have widespread metastases. The prolongation of patient survival by current
      treatment regimens has revealed a growing number of ODG patients with metastases.
      We believe that back pain complaints in patients with ODG should be viewed as an
      indicator of metastasis.

PMID- 30283559
TI  - Foramen Magnum Chordoid Meningioma in a 22-Year-old Female.
AB  - Chordoid meningioma is a rare variety of meningioma (0.5%-1%) with high rate of
      recurrence. They are grouped in WHO Grade II tumors. They are mainly distributed
      in the supratentorial location. There has been a single report of foramen magnum
      chordoid meningioma in a 3-year, 6-month-old child. Our patient, a 22-year-old
      female, admitted with progressive spastic quadriparesis with bowel and bladder
      involvement. She was operated with tumor resection done; postoperatively, patient
      showed dramatic improvement in the motor power as well as bowel and bladder
      function. Histopathology was suggestive of chordoid meningioma. She received 54
      Gy of radiotherapy. She is doing well with no neurological deficits and no
      recurrence at 2-year follow-up.

PMID- 30283560
TI  - Impar Ganglion Block with Combination of Neurolysis Drugs and Radiofrequency
      Thermocoagulation for Perineal Pain.
AB  - Since it was first introduced, a variety of modification techniques to block the
      impar ganglion appear such as transsacrococcygeal ligament technique,
      sacrococcygeal transdiscal approach, paramedian approach, and a two-needle
      technique using fluoroscopy or computed tomography scan. For therapeutic
      purposes, a combination of steroid and local anesthetic, neurolysis agents such
      as alcohol, phenol, cryolesioning, and heat lesioning using radiofrequency
      thermocoagulation could be used. Here, we reported a successful outcome in
      treating chronic perineal pain in a 65-year-old patient using combination of
      neurolysis agent which was alcohol 96% and radiofrequency thermocoagulation.

PMID- 30283561
TI  - Major Depression and Obsessive-compulsive Disorder Treated with Deep Brain
      Stimulation of Bilateral Nucleus Accumbens: The First Case of Turkey.
AB  - Deep brain stimulation (DBS) is a new alternative treatment for treatment
      resistant major depression (MD) and obsessive-compulsive disorder (OCD). Various
      DBS targets were defined for MD and OCD. Nucleus accumbens (NAcc) comes out among
      the other targets in patients with MD and comorbid OCD when physiopathology and
      limited side effects are taken into account. We report a 27-year-old male with MD
      and OCD who was treated by bilateral NAcc-DBS. The aim of this study is to
      discuss NAcc as a DBS target in patients with MD and OCD and to report the first
      case of a psychiatric disorder treated with DBS in Turkey.

PMID- 30283562
TI  - A Rare Case of Isolated Intracranial Rosai-Dorfman Disease Mimicking Optic Nerve
      Meningioma: A Case Report and Literature Review.
AB  - Sinus histiocytosis with massive lymphadenopathy, or Rosai-Dorfman disease (RDD),
      was first described in 1969 as a reactive condition of unknown etiology that is
      characterized by a proliferation of histiocytes exhibiting emperipolesis of both
      lymphocytes and plasma cells. It usually presents with painless cervical
      lymphadenopathy either with or without extranodal manifestations. Intracranial
      involvement of this disease is extremely rare. Intracranial RDD occurs in <5% of
      all patients with extranodal disease. Here, we report a case of RDD with isolated
      intracranial involvement. A 67-year-old male presented with a long-standing
      headache, retro-ocular pain, and progressive visual loss of the left eye.
      Magnetic resonance imaging showed features of optic nerve meningioma. The
      histopathology revealed sheets of histiocytes displaying emperipolesis. These
      histiocytes were S100 positive; however, a CD1a and epithelial membrane antigen
      were negative.

PMID- 30283563
TI  - Methotrexate-induced Leukoencephalopathy without Typical Restricted Diffusion on
      Diffusion-weighted Imaging and the Utility of Magnetic Resonance Spectroscopy to
      Support the Diagnosis.
AB  - Methotrexate (MTX) is a common antimetabolite agent that is widely used today in
      treating leukemia, lymphoma, and osteosarcoma. Its use has been associated with
      leukoencephalopathy causing seizures, paralysis, and even coma. To achieve the
      best possible outcome, it is important to be able to make a prompt diagnosis.
      Studies reported restricted diffusion on diffusion-weighted imaging (DWI) which
      is a reliable early sign of acute MTX-induced leukoencephalopathy. However, we
      report here the first case of MTX-induced leukoencephalopathy without typical
      restricted diffusion on DWI and the utility magnetic resonance spectroscopy to
      support this diagnosis in the difficult case such as the one being presented
      here.

PMID- 30283564
TI  - "The Subdural Collection" a Great Simulator: Case Report and Literature Review.
AB  - Prostate carcinoma rarely develops intracranial metastasis. In case it does, the
      dura is the most affacted area. In general, brain computed tomography (CT)
      findings mimic subdural hematoma making surgery challenge. We report the case of
      a 52-year-old male, presented as an emergency with a month history of headache,
      progressive temporospatial disorientation, mental confusion, and abrupt
      consciousness deterioration up to coma occurring few hours prior admission. An
      urgent brain CT scan showed a subdural collection in favor of a chronic subdural
      hematoma. The patient underwent surgery by standard burr hole, and surprisingly,
      peroperatively, there was a very bloody diffuse thickening of the dura without a
      real hematoma obliging to switch to a large fronto-temporoparietal craniotomy
      revealing a subdural mass that was completely removed. Histopathology disclosed a
      metastatic prostatic carcinoma confirming that such a subdural collection could
      behave as a great simulator. A contrast brain CT scan, is advisable, even in
      emergency, in selected case, with atypical images finding, especially if, a
      malignant disease is already known; the former could be of great help in the
      differential diagnosis and the best prompt management.

PMID- 30283565
TI  - Intracranial Hypertension Secondary to Cervical Dural Arteriovenous Fistula.
AB  - Idiopathic intracranial hypertension (IIH) is a disease of mainly unknown
      etiology. Latest theories as to the pathogenesis have postulated a final common
      pathway of cerebral venous hypertension secondary to venous outflow impairment
      leading to decreased cerebrospinal fluid absorption. We present the case of a 42
      year-old female who was treated for several years for headache and for
      approximately 12 months for IIH until appropriate imaging showed a right-sided
      cervical dural arteriovenous fistula (AVF) at the level of C4. The patient's IIH
      symptoms resolved following surgical excision of the fistula. We suggest that the
      cranial venous outflow impairment secondary to the cervical AVF was responsible
      for intracranial hypertension and that complete investigation of IIH patients
      should include imaging of the neck vasculature.

PMID- 30283566
TI  - Iodinated Contrast Encephalopathy after Coil Embolization of Unruptured
      Aneurysms.
AB  - Iodinated contrast encephalopathy is known as one of the rare complications of
      cerebral angiography and neurovascular intervention. The mechanism and causes of
      contrast encephalopathy are not understood well. In this case, we experienced
      transient neurological deficit following coil embolization of unruptured
      aneurysms. A 67-year-old woman with two unruptured aneurysms of internal carotid
      artery underwent endovascular coil embolization. During the procedure, she
      presented transient hemiparesis and aphasia. After the treatment, she presented
      the symptom again, and computed tomography scan showed cortical edema and
      subarachnoid leakage of contrast agent. Magnetic resonance imaging excluded
      cerebral infarction. The neurological symptom resolved completely within 24 h
      after the treatment, and she was diagnosed as the contrast encephalopathy. In our
      case, we speculated that contrast encephalopathy has occurred subsequently to the
      transient cerebral ischemia. Iodinated contrast encephalopathy may have induced
      with neurovascular intervention following cerebral ischemia and increased use of
      contrast agent. We should consider iodinated contrast encephalopathy when a
      patient presents hemiparesis and aphasia such as that caused by acute stroke
      during neurovascular intervention.

PMID- 30283567
TI  - Persistent Primitive Trigeminal Artery Associated With Anterior Communicating
      Artery Aneurysm and Hypoplastic Vertebral Artery.
AB  - The persistent trigeminal artery is one of the presegmental arteries in the
      embryonic period; in some rare cases, it is associated with cerebral aneurysm but
      as a cause of subarachnoid hemorrhage (SAH) has not been described in the
      literature. We report a patient who presented a Fisher IV SAH associated with a
      ruptured intracranial aneurysm. The performed cerebral angiography demonstrated
      the presence of aneurysm in the anterior communicating artery associated to
      hypoplastic vertebral artery on the same side. We considered those finding
      coincidental. The coexistence of saccular aneurysm with anatomical variations in
      the intracranial vasculature is briefly discussed. It was managed by endovascular
      embolization. The patient returned to normal activities.

PMID- 30283569
TI  - Delayed Paraplegia in an Adult Patient With Spinal Cord Injury without
      Radiographic Abnormality of Dorsal Spine: A Lesson Learned.
AB  - Noncompressive myelopathy of lower dorsal spine secondary to trauma is a rare
      event. We report a case of delayed paraplegia in a patient with a history of road
      traffic accident. The X-ray of dorsolumbar spine did not show any abnormality.
      Magnetic resonance imaging of dorsolumbar spine was performed which showed the
      presence of central T2-weighted hyperintensities from D10-D11 to D12-L1 level. No
      associated bony injury was documented, and the integrity of the spinal canal was
      maintained. The patient was managed conservatively with bed rest, and steroids
      were given. However, the patient did not show any signs of improvement after 1
      month of follow-up.

PMID- 30283568
TI  - Paraneoplastic Nephrotic Syndrome in a Patient with Planum Sphenoidale
      Meningioma.
AB  - A 60-year-old homemaker presenting with pedal edema and ascites was found to have
      a planum sphenoidale meningioma concurrently with nephrotic syndrome. On renal
      biopsy, the patient was found to have membranous glomerulonephritis. There was
      complete remission of nephropathy after excision of the meningioma. Nephrotic
      syndrome has been commonly found in association with malignancies and blood
      disorders but the association with a meningioma is extremely rare, and only one
      case has been previously reported as per our knowledge.

PMID- 30283571
TI  - Pediatric Suprasellar Atypical Teratoid Rhabdoid Tumor Arising from the Third
      Ventricle: A Rare Tumor at a Very Rare Location.
AB  - Atypical teratoid rhabdoid tumor (ATRT) is a rare, highly malignant tumor of the
      central nervous system, commonly affecting children below 3 years of age, with
      around 300 cases reported in the literature. Suprasellar area is a very rare
      location for such tumor in the pediatric population, with technical difficulties
      in complete excision. Third ventricular ATRT is very rare. Here, we report the
      case of a 2-year-old male child who presented with lethargy and vomiting. He had
      features of raised intracranial pressure with reduced vision in both eyes.
      Magnetic resonance imaging of the brain revealed a heterogeneously enhancing
      lobulated giant lesion in the suprasellar location, occupying the third ventricle
      and hypothalamus with encasement of both carotids. He underwent pericoronal
      parasagittal craniotomy, interhemispheric transcallosal interforniceal approach
      and gross total excision of the lesion. Postoperatively, the child had altered
      sensorium and diabetes insipidus, both of which recovered over a span of 10 days.
      Histopathological examination of the specimen was consistent with the diagnosis
      of World Health Organization Grade IV ATRT. In spite of all our efforts, he
      succumbed to his illness 5 months postoperatively.

PMID- 30283570
TI  - Delayed Occurrence of C3 Vertebra Anterior Subluxation Diagnosed after Surgery
      for Epidural Hematoma.
AB  - A case of delayed occurrence of C3 vertebra anterior subluxation diagnosed 10
      days after surgery for epidural hematoma is herein described. A 56-year-old man
      underwent surgery for right epidural hematoma. No spinal fracture was identified
      on the cervical-spinal computed tomography (CT) on arrival. The patient developed
      neck pain after the craniotomy, and cervical magnetic resonance imaging 5 days
      postoperatively revealed a disruption of the C3-C4 posterior ligament complex.
      The patient was conservatively treated with immobilization. Cervical CT 10 days
      postoperatively revealed C3 vertebra anterior subluxation. Posterior fixation
      surgery was performed 21 days after admission, and the postoperative course was
      uneventful. This case suggests that awareness of delayed occurrence of cervical
      dislocation after traumatic intracranial hemorrhage should be increased among
      neurosurgeons.

PMID- 30283572
TI  - A Rare Case Report of Giant Cell Tumor of the Sphenoid Bone in a Patient Who
      Developed "Erythema Multiforme Associated with Phenytoin and Cranial Radiation
      Therapy Syndrome".
AB  - Giant cell tumors (GCTs) are rare, usually affecting the epiphyses in long bones
      of the extremities. GCTs may be locally aggressive with a high rate of local
      recurrence and exhibit the potential for distant metastasis. They seldom occur in
      the skull, where they preferentially affect the sphenoid and temporal bones.
      Several case reports with follow-up describe gross total resection of skull-base
      GCT to be curative. Radiation therapy, although controversial, is reserved for
      lesions that cannot be completely resected. Here, we describe the case of an 18
      year-old female with GCT of sphenoid bone who underwent subtotal resection
      followed by adjuvant radiotherapy, although whose radiotherapy could not be
      completed because of her demise due to erythema multiforme associated with
      phenytoin and cranial radiation therapy syndrome.

PMID- 30283573
TI  - Melanotic Schwannoma of Spine: Illustration of Two Cases with Diverse Clinical
      Presentation and Outcome.
AB  - Melanotic schwannomas (MS) are rare variants of schwannomas the occurrence of
      which is described in case reports only. They usually arise from posterior spinal
      nerve roots and less commonly from other cells of neural crest origin. Although
      they are relatively benign tumors in young, aggressive behavior is reported. They
      occur as isolated tumors or as part of a syndrome named Carney complex. We try to
      describe the pathology, diagnosis, management, and prognosis of MSs in two
      different cases: one cervical intramedullary with no recurrence on 5-year follow
      up and the other one extramedullary in lumbar region with early recurrence and
      aggressive course. A brief review of literature is done.

PMID- 30283574
TI  - A Rare Case of Simultaneous Multifocal Craniospinal Hemangiopericytomas.
AB  - First reported case of simultaneous occurrence of hemangiopericytomas(HCP) at
      multiple sites of craniospinal axis in a thirty four year male is presented.
      Patient presented with neck pain for 1 year, and one episode of simple partial
      seizure involving his left lower limb. He was diagnosed as having HCP in right
      middle one third parasagittal region, and C4,5 vertebral bodies. Another lesion
      was present in L5 vertebra, which was radiologically similar to the cervical
      lesion, but not biopsy proven. High index of suspicion, and low threshold for
      screening, for coexistence of spinal HCP, in patients harboring cranial HCP's and
      complaints of back pain.

PMID- 30283576
TI  - Management of Recurrent Tumefactive Multiple Sclerosis: Case Report and
      Literature Review.
AB  - Tumefactive multiple sclerosis (MS) is characterized by the presence of a single
      MS-plaque in the brain. It mimics tumors due to large size, mass effect, and
      enhancement patterns. Refractory intracranial hypertension due to tumefactive MS
      requiring decompressive craniectomy (DC) was reported in five cases. However,
      none of these cases were documented new lesions during the follow-up. We report a
      case of a 28-year-old female admitted with acute right hemiparesis, headache, and
      nausea. A brain magnetic resonance imaging (MRI) revealed a left parietal lobe
      lesion. Within 4 days, she became comatose. Computed tomography (CT) scan
      revealed the left uncal herniation. DC and resection of the lesion were carried
      out. Histopathology revealed active demyelinating disease. After 11 years of the
      first attack, she went to the emergency department due to headache and left
      hemiparesis. Head CT scan revealed a hypodense area in the right frontal lobe.
      Three months later, the patient was asymptomatic, and new MRI did not show new
      lesions.

PMID- 30283575
TI  - The Role of Endoscopic Endonasal Approach in the Multimodal Management of Giant
      Pituitary Adenoma: Case Report and Literature Review.
AB  - Giant pituitary adenomas (GPAs) are defined as pituitary lesions larger than 40
      mm of diameter. Surgical resection remains the gold standard to decompress the
      optic apparatus, reduce lesion load, and preserve hormonal function. The
      endoscopic endonasal approach (EEA) has been increasingly used for the treatment
      of pituitary adenomas and skull base tumors due to the wide angle of view and
      exposure. Through the description of an exemplificative case of EEA resection of
      a nonsecreting GPA in the setting of a multimodal treatment, the authors discuss
      the advantages and disadvantages of this management strategy and provide a
      detailed review of the literature.

PMID- 30283577
TI  - Feasibility of a Fourth Ventriculopleural Shunt for Diversion of an Isolated
      Fourth Ventricle: A Technical Note.
AB  - Isolated fourth ventricle syndrome is an uncommon entity due to obstruction of
      both inlet and outflow foramina. The resulting mass effect from the progressively
      expanding fourth ventricle may cause symptoms from both cerebellar and brainstem
      compression. Although a variety of treatment modalities have been advocated for
      this condition, an in-depth description of placement of a fourth
      ventriculopleural (VPL) shunt from a single-stage prone approach has not yet been
      published in the literature. We describe here a case of successful placement of a
      fourth VPL shunt in a 22-year-old female with a history of a prior posterior
      fossa pilocytic astrocytoma resection who presented with symptomatic isolated
      fourth ventricular hydrocephalus.

PMID- 30283578
TI  - Recurrent Embolic Stroke Caused by Large Cavernous Carotid Aneurysm: Stroke
      Recurrence Prevention with High-Flow Bypass Followed by Proximal Occlusion.
AB  - Intracranial aneurysms may cause embolic stroke. Medical or surgical management
      is selected on an individual basis, as the optimal treatment strategy has not
      been established. A 79-year-old woman with a large cavernous carotid aneurysm
      suffered repeated embolic stroke after enlargement and partial thrombosis of the
      aneurysm, in spite of antiplatelet therapy. Coil embolization of the primitive
      trigeminal artery and ligation of the internal carotid artery (ICA) at the
      cervical portion followed by high-flow bypass from the cervical external carotid
      artery to the middle cerebral artery were performed. The aneurysm was thrombosed,
      and prevention of further stroke was achieved. Acute enlargement and thrombosis
      of large or giant cavernous carotid aneurysm may cause repeated embolic stroke,
      and requires emergent exclusion of the aneurysm from circulation by proximal ICA
      occlusion together with distal revascularization before devastating embolic
      stroke occurs.

PMID- 30283579
TI  - Traumatic Chance Fracture of Cervical Spine: A Rare Fracture Type and Surgical
      Management.
AB  - Cervical spine chance fracture (flexion-distraction) is a rare type of fracture,
      and the surgical management remains a dilemma to the neurosurgeons as there is a
      paucity of evidence accordingly. We herein report a traumatic chance fracture of
      C7 fractures and its surgical management. A 33-year-old male was transferred to
      our center after being hit as pedestrian and was diagnosed to have a chance
      fracture of C7 and bilateral C7 root injury. He underwent open reduction of the
      deformity by posterior-only fixation of C5 and C6 with a lateral mass screw and
      T1 and T2 with pedicular screws. The neurological examination improved
      postoperatively, and the patients were neurologically intact after 6 months of
      treatment. Traumatic cervical spine chance fracture is extremely rare and can be
      managed surgically through posterior fixation and open reduction of the
      deformity. The best choice of treatment is limited by the paucity of the evidence
      and should be individualized.

PMID- 30283580
TI  - Dissecting Aneurysm of Vertebral Artery Involving the Origin of Posteroinferior
      Cerebellar Artery Treated with Retrograde Stent Placement and Coil Embolization
      in the Era of Flow Diverter.
AB  - Ruptured vertebral artery (VA) dissecting aneurysm carries high risk of rerupture
      and mortality if not treated immediately. Dissecting aneurysm of the VA involving
      the posteroinferior cerebellar artery (PICA) origin is difficult to treat by
      surgical and endovascular route. With the availability of flow diversion device
      for reconstructive procedure, endovascular treatment has now become easy to treat
      difficult aneurysm while maintaining the patency of the PICA. However, instead of
      using flow diverter (FD) in our case, we successfully treated dissecting VA
      aneurysm involving the PICA origin with retrograde stent placement from distal
      right VA to the left PICA to maintain the patency of PICA and occlusion of
      dissecting aneurysm of VA with detachable coils instead of performing surgical
      bypass and FD placement.

PMID- 30283581
TI  - Iatrogenic (Traumatic) Occipital Artery Pseudoaneurysm - Rare Complication of
      Ventriculoperitoneal Shunt in an Infant: Case Report and Review of the
      Literature.
AB  - Although ventriculoperitoneal shunt (VPS) is the most common procedure performed
      by pediatric neurosurgeons, it is still associated with frustrating
      complications, most common of which are obstruction and infection. Traumatic
      occipital artery pseudoaneurysm is a very rare complication of VPS procedure. To
      the best of our knowledge, there is no similar case reported in the English
      language literature. A 12-month-old patient suffered posthemorrhagic
      hydrocephalus of prematurity, and multiple other complications due to extreme
      prematurity, including immature lung disease, retinopathy of prematurity,
      necrotizing enterocolitis, bowel perforation, short bowel syndrome resulting in
      total parenteral nutrition-dependence, and hydrocephalus which was treated by
      insertion of VPS. Four weeks after the shunt, a slowly enlarging pulsatile
      swelling distal to the valve under the catheter altering the shunt function was
      noted. The swelling was diagnosed as a pseudoaneurysm of the occipital artery and
      treated by excision of the aneurysm. The child developed isolated dilated fourth
      ventricle, which was treated by endoscopic fourth ventriculostomy. Traumatic
      occipital artery pseudoaneurysm as a result of tunneling of VPS catheter is a
      very rare complication of VPS. Clinical and radiological imaging is diagnostic of
      the aneurysm. Surgical repair should be considered in such cases. This case
      report is aimed to raise the awareness among physicians about this rare
      complication.

PMID- 30283582
TI  - Natural History of Medulloblastoma in a Child with Neurofibromatosis Type I.
AB  - Medulloblastoma is one of the common posterior fossa tumors in children. The
      natural history of this tumor in presymptomatic period is not well known.
      Widespread use of brain imaging has increased the detection of incidental brain
      tumors in totally asymptomatic persons. Here, we report a case of a 4-year-old
      boy with prenatal diagnosis of congenital brain abnormalities and
      neurofibromatosis type I. He underwent regular brain imaging to follow
      interhemispheric arachnoid cyst and ventriculomegaly that a posterior fossa tumor
      was discovered. The tumor size increased during time and became symptomatic after
      28 months which was resected.

PMID- 30283583
TI  - Heterotrophic Ossification of the Flexor Retinaculum in a Patient with Ankylosing
      Spondylitis.
AB  - Carpal tunnel syndrome (CTS) is the most common peripheral neuropathy. This
      syndrome has various etiologies of which heterotopic ossification of the flexor
      retinaculum is a rare cause. Ankylosing spondylitis (AS) is a systemic,
      progressive inflammatory disease of unknown etiology that mainly affects the
      axial skeleton and rarely causes peripheral neurological symptoms. A 48-year-old
      woman presented with numbness and pain in her right hand. Ten years earlier, she
      was diagnosed with AS. Electrodiagnostic evaluation revealed severe median nerve
      compression at the right wrist. The patient underwent surgery for severe CTS.
      During the operation, the flexor retinaculum could not be incised due to marked
      stiffness. Ossification of the flexor retinaculum was seen, and the retinaculum
      was partially excised with an osteotome and Kerrison rongeur. The patient's
      complaints resolved almost totally after the operation. AS is a common systemic
      inflammatory disease that can produce heterotopic ossification of the flexor
      retinaculum. Preoperative wrist computed tomography should be obtained in
      patients with CTS and AS.

PMID- 30283584
TI  - Primary Intracranial Manifestation of a Carcinosarcoma.
AB  - Carcinosarcomas are tumors comprising part adenocarcinoma and part sarcoma; the
      presence of carcinosarcoma in the head-and-neck region is very rare. These tumors
      are typically highly aggressive (G3) and arise most frequently from the salivary
      gland. Here, we present a case report on a brain metastasis as the primary
      manifestation of a carcinosarcoma. Magnetic resonance imaging showed a tumor of
      the pineal region with infiltration of the brainstem and the corpus. The staging
      following the histopathological diagnosis revealed the origin of the tumor in the
      left parotid gland. We present an overview of the significance of published
      treatment strategies in carcinosarcoma.

PMID- 30283585
TI  - Intradural Extramedullary Tuberculoma Masquerading En Plaque Meningioma.
AB  - Extensive en plaque intradural extramedullary tuberculomas can occur as a
      paradoxical response to chemotherapy for intracranial tuberculomas. We report a
      case of 31-year-old male who presented with backache and progressive weakness and
      urgency of micturition. Magnetic resonance imaging dorsolumbar spine which showed
      an ill-defined T1 hypointense and T2 heterointense lesion noted posterior to the
      thoracic spinal cord, extending from C7 to D5 vertebral levels suggestive of en
      plaque meningioma. The patient underwent D1-D5 laminectomy, with subtotal
      debulking of the tumor. The histopathological examination of lesion was
      suggestive of granulomatous inflammation with multinucleated and Langhan type
      giant cells confirming the diagnosis of tuberculoma.

PMID- 30283586
TI  - Subdural Hematoma as a Consequence of Labor Epidural Analgesia.
AB  - Subdural hematoma (SDH) following labor epidural analgesia is a rare neurological
      complication. SDH is a late complication of this procedure; it is caused by a
      leak of cerebrospinal fluid that may damage the vascular structures of the brain.
      Persistent headache in the days after labor epidural analgesia is a nonspecific
      clinical symptom caused by hematoma. Preexisting vascular malformations can be a
      concomitant cause of headache. Clinical cases have been reported even after
      epidural anesthesia. The differential diagnosis includes unspecified headache,
      sinusitis headache, drug-induced headache, cortical vein thrombosis, fistula of
      the dura mater, and bacterial, viral, and aseptic meningitis.

PMID- 30283587
TI  - Isolated Orbital Roof Fracture: Can It Be Catastrophic?
AB  - Orbital encephalocele is a rare catastrophic complication of orbital roof
      fractures. Early diagnosis of this posttraumatic orbital encephalocele is very
      crucial because this condition if untreated leads to rapid loss of vision.
      Whenever displaced orbital roof fracture is identified in a head injury patient,
      an orbital encephalocele should be suspected. Although magnetic resonance imaging
      is the investigation of choice, computed tomography of orbit with thin axial and
      coronal sequences often gives the diagnosis. Frontobasal approach is the most
      commonly used surgical approach. Supra-transorbital approach is a minimally
      invasive alternative. Good results with regard to the orbital symptoms can be
      expected.

PMID- 30283588
TI  - Cerebral Bypass Surgery for Internal Carotid Artery Occlusion, Complex
      Supraclinoid Carotid Artery Aneurysm, and Tumors: A Report of Four Cases.
AB  - Despite growing popularity of endovascular techniques, certain subsets of
      patients with cerebrovascular compromise may benefit from bypass surgery. We
      present four cases in which pending ischemic lesion was prevented by (1) A3
      resection and reanastomosis following falx meningioma removal, (2) rescue
      superficial temporal artery-middle cerebral artery (STA-MCA) bypass after
      pituitary adenoma surgery, (3) STA-MCA bypass for chronic internal carotid artery
      occlusion, and (4) external carotid artery-MCA bypass using radial artery
      grafting. Following the procedure, there were no further clinical or radiological
      deteriorations and long-term patency was confirmed in all four cases.

PMID- 30283590
TI  - Trans-Cranial Embolisation of a Complex Transverse Sigmoid Sinus Dural
      Arteriovenous Fistula by Direct Puncture of the Superior Sagittal Sinus.
AB  - This technical note describes a direct puncture of the superior sagittal sinus
      (SSS) to treat a complex dural arteriovenous fistula (dAVF). A 40-year-old female
      was admitted having a history of increasing confusion. Computer tomography
      revealed enlargement of the right superior ophthalmic vein and magnetic resonance
      imaging demonstrated extensive bilateral hemispheric venous engorgement. Digital
      subtraction angiography (DSA) demonstrated a high flow dAVF involving the right
      transverse sinus. There was extensive cortical venous rerouting with venous sinus
      occlusion at the right transverse and sigmoid junction. Under general anesthesia,
      the sinus was exposed and catheterized. The angiography catheter was fed over the
      guide wire into the sinus. The remaining right sigmoid and transverse sinus were
      obliterated using a combination of microcoils and Onyx(r). She made a good
      postoperative recovery, and a repeat DSA at 30 days postoperatively showed
      evidence of the meningohypophyseal trunk but complete occlusion of the fistula. A
      check DSA 2 years later confirmed no evidence of a residual fistula. Our case
      demonstrates the potential use of the SSS as a novel conduit to treat distant
      targets.

PMID- 30283589
TI  - The Orbitomeningeal Band as a Way to Bloodless Transcavernous Dissection and
      Anterior Clinoidectomy.
AB  - The meningo-orbital band (MOB) is a dural fold which runs along the lateral
      border of the superior orbital fissure and contains few small dural veins and the
      orbitomeningeal artery. MOB detachment is relatively easy to understand step-wise
      procedure, provides a wider exposure, and better orientation thus facilitating
      relatively easy approach to paraclinoid and cavernous sinus region. The present
      microsurgical technique helps to preserve the true cavernous membrane and thereby
      providing almost bloodless dissection of the cavernous sinus. The same technique
      can be used to uncover the anterior clinoid process laterally, posteriorly,
      superiorly, and also in the inferolateral region thereby decreasing the risk and
      time of clinoidectomy.

PMID- 30283591
TI  - Multiple Thoracic Spinal Lesions Causing Spinal Cord Compression Secondary to
      Multiple Myeloma in a Patient with Synchronously Diagnosed Renal Cell Carcinoma:
      Value of Lesional Biopsy!

PMID- 30283592
TI  - Conservative Management of Chronic Subdural Hematoma with Tranexamic Acid.

PMID- 30283593
TI  - Supracerebellar Approach to Epidermoid Tumors.

PMID- 30283594
TI  - Prehospital Care for Head Trauma.

PMID- 30283595
TI  - Erratum: Anaphylactic Reaction after Autologous Blood Transfusion: A Case Report
      and Review of the Literature.
AB  - [This corrects the article on p. 145 in vol. 10.].

PMID- 30283596
TI  - Associations between Practitioner Personality and Client Quit Rates in Smoking
      Cessation Behavioural Support Interventions.
AB  - Introduction: There is wide variation in the success rates of practitioners
      employed to help smokers to stop, even once a range of potential confounding
      factors has been taken into account. Aim: This paper examined whether personality
      characteristics of practitioners might play a role success rates. Methods: Data
      from 1,958 stop-smoking treatment episodes in two stop-smoking services (SSS)
      involving 19 stop-smoking practitioners were used in the analysis. The outcome
      measure was clients' biochemically verified quit status 4 weeks after the target
      quit date. The five dimensions of personality, as assessed by the Ten-Item
      Personality Inventory, were included as predictor variables: openness,
      conscientiousness, agreeableness, extraversion, and neuroticism. A range of
      client and other practitioner characteristics were used as covariates. A
      sensitivity analysis was conducted to determine if managers' ratings of
      practitioner personality were also associated with clients' quit status. Results:
      Multi-level random intercept models indicated that clients of practitioners with
      a higher extraversion score had greater odds of being abstinent at four weeks
      (self-assessed: OR = 1.10, 95% CI = 1.01-1.19; manager-assessed: OR = 1.32, 95%
      CI = 1.21-1.44). Conclusions: More extraverted stop smoking practitioners appear
      to have greater success in advising their clients to quit smoking. Findings need
      to be confirmed in larger practitioner populations, other SSS, and in different
      smoking cessation contexts. If confirmed, specific training may be needed to
      assist more introverted stop smoking practitioners.

PMID- 30283597
TI  - Clinical update on the management of pseudopapillary tumor of pancreas.
AB  - Solid pseudopapillary neoplasm (SPN) is a rare tumor with malignant potential
      which is generally located in the tail of pancreas. The prevalence of SPN has
      increased with widespread use of cross sectional imaging. SPN is often
      misdiagnosed due to nonspecific clinical presentation and accurate diagnosis is
      essential for optimal management. Endoscopic ultrasound-FNA with
      immunohistochemistry can help in preoperative diagnosis. Surgery is the treatment
      of choice and a successful R0 resection is curative. Overall, SPN has a good
      prognosis. This review article focuses on pathogenesis, diagnosis and management
      of SPN.

PMID- 30283598
TI  - Endoscopic diagnosis and treatment of superficial non-ampullary duodenal tumors.
AB  - The diagnostic and treatment guidelines of superficial non-ampullary duodenal
      tumors have not been standardized due to their low prevalence. Previous reports
      suggested that a superficial adenocarcinoma (SAC) should be treated via local
      resection because of its low risk of lymph node metastasis, whereas a high-grade
      adenoma (HGA) should be resected because of its high risk of progression to
      adenocarcinoma. Therefore, pretreatment diagnosis of SAC or HGA is important to
      determine the appropriate treatment strategy. There are certain endoscopic
      features known to be associated with SAC or HGA, and current practice prioritizes
      the endoscopic and biopsy diagnosis of these conditions. Surgical treatment of
      these duodenal lesions is often related to high risk of morbidity, and therefore
      endoscopic resection has become increasingly common in recent years. Endoscopic
      mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are the
      commonly performed endoscopic resection methods. EMR is preferred due to its
      lower risk of adverse events; however, it has a higher risk of recurrence than
      ESD. Recently, a new and safer endoscopic procedure that reduces adverse events
      from EMR or ESD has been reported.

PMID- 30283600
TI  - Proposed approach to the challenging management of progressive gastroesophageal
      reflux disease.
AB  - The progression of gastroesophageal reflux disease (GERD) in patients who are
      taking proton pump inhibitors (PPIs) has been reported by several investigators,
      leading to concerns that PPI therapy does not address all aspects of the disease.
      Patients who are at risk of progression need to be identified early in the course
      of their disease in order to receive preventive treatment. A review of the
      literature on GERD progression to Barrett's esophagus and the associated
      physiological and pathological changes was performed and risk factors for
      progression were identified. In addition, a potential approach to the prevention
      of progression is discussed. Current evidence shows that GERD can progress;
      however, patients at risk of progression may not be identified early enough for
      it to be prevented. Biopsies of the squamocolumnar junction that show microscopic
      intestinalization of metaplastic cardiac mucosa in endoscopically normal patients
      are predictive of future visible Barrett's esophagus, and an indicator of GERD
      progression. Such changes can be identified only through biopsy, which is not
      currently recommended for endoscopically normal patients. GERD treatment should
      aim to prevent progression. We propose that endoscopically normal patients who
      partially respond or do not respond to PPI therapy undergo routine biopsies at
      the squamocolumnar junction to identify histological changes that may predict
      future progression. This will allow earlier intervention, aimed at preventing
      Barrett's esophagus.

PMID- 30283599
TI  - Endoscopic therapy for Barrett's esophagus and early esophageal cancer: Where do
      we go from here?
AB  - Since Barrett's esophagus is a precancerous condition, efforts have been made for
      its eradication by various ablative techniques. Initially, laser ablation was
      attempted in non-dysplastic Barrett's esophagus and subsequently, endoscopic
      ablation using photodynamic therapy was used in Barrett's patients with high
      grade dysplasia who were poor surgical candidates. Since then, various ablative
      therapies have been developed with radiofrequency ablation having the best
      quality of evidence. Resection of dysplastic areas only without complete removal
      of entire Barrett's segment is associated with high risk of developing
      metachronous neoplasia. Hence, the current standard of management for Barrett's
      esophagus includes endoscopic mucosal resection of visible abnormalities followed
      by ablation to eradicate remaining Barrett's epithelium. Although endoscopic
      therapy cannot address regional lymph node metastases, such nodal involvement is
      present in only 1% to 2% of patients with intramucosal adenocarcinoma in Barrett
      esophagus and therefore is useful in intramucosal cancers. Post ablation
      surveillance is recommended as recurrence of intestinal metaplasia and dysplasia
      have been reported. This review includes a discussion of the technique, efficacy
      and complication rate of currently available ablation techniques such as
      radiofrequency ablation, cryotherapy, argon plasma coagulation and photodynamic
      therapy as well as endoscopic mucosal resection. A brief discussion of the
      emerging technique, endoscopic submucosal dissection is also included.

PMID- 30283602
TI  - Anesthetic management and associated complications of peroral endoscopic myotomy:
      A case series.
AB  - AIM: To investigate the anesthetic management of peroral endoscopic myotomy
      (POEM) and its associated complications. METHODS: This study was a single-center,
      retrospective, observational study comprising a case series of all patients who
      underwent POEM in our hospital from April 2015 to November 2016. We collected
      data regarding patient characteristics, anesthetic methods, surgical factors, and
      complications using an electronic chart. RESULTS: There were 86 patients who
      underwent POEM in our hospital during the study period. Preoperatively, patients
      were maintained on a low residue diet for 48 h prior to the procedure. They were
      fasted of solids for 24 h before surgery. There was one case of aspiration
      (1.2%). During POEM, patients were positioned supine with the upper abdomen
      covered by a clear drape so that pneumoperitoneum could be timeously identified.
      In three cases, the peak airway pressure exceeded 35 cmH2O during volume
      controlled ventilation with tidal volumes of 6-8 mL/kg and subsequent impairment
      of ventilation. These cases had been diagnosed with spastic esophageal disorders
      (SEDs) and the length of the muscular incision on the esophageal side was longer
      than normal. CONCLUSION: In the anesthetic management of POEM, it is important to
      prevent aspiration during induction of anesthesia and to identify and treat
      complications associated with CO2 insufflation.

PMID- 30283601
TI  - Capsule endoscopy: Current status and role in Crohn's disease.
AB  - Capsule endoscopy (CE) has proved to be an important non-invasive tool for
      diagnosis and monitoring Crohn's disease patients. It has the advantage of
      excellent visualization of digestive tract mucosa, a good tolerability and safety
      in well-selected patients. The risk of retention can be diminished by good
      selection of patients using imaging techniques and by the use of patency capsule.
      The aim of a capsule examination is not only an early diagnosis but also a very
      good stratification of prognosis, thus directing the treatment strategy for
      either a step up or top-down approach and also permitting the optimization of the
      treatment depending on the findings. When symptoms and biomarkers point to a
      change in the disease's activity we can either adjust the treatment directly as
      recommended in CALM study or choose in selected patients to visualize the
      digestive mucosa through a CE and take a decision afterwards. The appearance of
      the new capsule from Medtronic-the Pillcam Crohn's might be an important step
      forward in diagnosis, evaluating disease extent, the severity of the disease,
      prognosis, management in a treat to target approach, with treatment modifications
      according to the data from CE examination. Serial examinations in the same
      patient can be compared and a more objective evaluation of the lesions
      modification from one exam to another can be performed. We present the latest
      developments and current status and evidence that in selected patients capsule
      can be a tool in a treat to target approach.

PMID- 30283603
TI  - Frequency of hospital readmission and care fragmentation in gastroparesis: A
      nationwide analysis.
AB  - AIM: To evaluate rates and predictors of hospital readmission and care
      fragmentation in patients hospitalized with gastroparesis. METHODS: We identified
      all adult hospitalizations with a primary diagnosis of gastroparesis in the 2010
      2014 National Readmissions Database, which captures statewide readmissions. We
      excluded patients who died during the hospitalization, and calculated 30 and 90-d
      unplanned readmission and care fragmentation rates. Readmission to a non-index
      hospital (i.e., different from the hospital of the index admission) was
      considered as care fragmentation. A multivariate Cox regression model was used to
      analyze predictors of 30-d readmissions. Logistic regression was used to
      determine hospital and patient factors independently associated with 30-d care
      fragmentation. Patients readmitted within 30 d were followed for 60 d post
      discharge from the first readmission. Mortality during the first readmission,
      hospitalization cost, length of stay, and rates of 60-d readmission were compared
      between those with and without care fragmentation. RESULTS: There were 30064
      admissions with a primary diagnosis of gastroparesis. The rates of 30 and 90-d
      readmissions were 26.8% and 45.6%, respectively. Younger age, male patient,
      diabetes, parenteral nutrition, >= 4 Elixhauser comorbidities, longer hospital
      stay (> 5 d), large and metropolitan hospital, and Medicaid insurance were
      associated with increased hazards of 30-d readmissions. Gastric surgery, routine
      discharge and private insurance were associated with lower 30-d readmissions. The
      rates of 30 and 90-d care fragmentation were 28.1% and 33.8%, respectively.
      Younger age, longer hospital stay (> 5 d), self-pay or Medicaid insurance were
      associated with increased risk of 30-d care fragmentation. Diabetes, enteral tube
      placement, parenteral nutrition, large metropolitan hospital, and routine
      discharge were associated with decreased risk of 30-d fragmentation. Patients who
      were readmitted to a non-index hospital had longer length of stay (6.5 vs 5.8 d,
      P = 0.03), and higher mean hospitalization cost ($15645 vs $12311, P < 0.0001),
      compared to those readmitted to the index hospital. There were no differences in
      mortality (1.0% vs 1.3%, P = 0.84), and 60-d readmission rate (55.3% vs 54.6%, P
      = 0.99) between the two groups. CONCLUSION: Several factors are associated with
      the high 30-d readmission and care fragmentation in gastroparesis. Knowledge of
      these predictors can play a role in implementing effective preventive
      interventions to high-risk patients.

PMID- 30283604
TI  - Randomised controlled trial comparing modified Sano's and narrow band imaging
      international colorectal endoscopic classifications for colorectal lesions.
AB  - AIM: To assess the utility of modified Sano's (MS) vs the narrow band imaging
      international colorectal endoscopic (NICE) classification in differentiating
      colorectal polyps. METHODS: Patients undergoing colonoscopy between 2013 and 2015
      were enrolled in this trial. Based on the MS or the NICE classifications,
      patients were randomised for real-time endoscopic diagnosis. This was followed by
      biopsies, endoscopic or surgical resection. The endoscopic diagnosis was then
      compared to the final (blinded) histopathology. The primary endpoint was the
      sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative
      predictive value (NPV) of differentiating neoplastic and non-neoplastic polyps
      (MS II/IIo / IIIa / IIIb vs I or NICE 1 vs 2/3). The secondary endpoints were
      "endoscopic resectability" (MS II/IIo/IIIa vs I/IIIb or NICE 2 vs 1/3), NPV for
      diminutive distal adenomas and prediction of post-polypectomy surveillance
      intervals. RESULTS: A total of 348 patients were evaluated. The Sn, Sp, PPV and
      NPV in differentiating neoplastic polyps from non-neoplastic polyps were, 98.9%,
      85.7%, 98.2% and 90.9% for MS; and 99.1%, 57.7%, 95.4% and 88.2% for NICE,
      respectively. The area under the receiver operating characteristic curve (AUC)
      for MS was 0.92 (95%CI: 0.86-0.98); and AUC for NICE was 0.78 (95%CI: 0.69,
      0.88). The Sn, Sp, PPV and NPV in predicting "endoscopic resectability" were
      98.9%, 86.1%, 97.8% and 92.5% for MS; and 98.6%, 66.7%, 94.7% and 88.9% for NICE,
      respectively. The AUC for MS was 0.92 (95%CI: 0.87-0.98); and the AUC for NICE
      was 0.83 (95%CI: 0.75-0.90). The AUC values were statistically different for both
      comparisons (P = 0.0165 and P = 0.0420, respectively). The accuracy for diagnosis
      of sessile serrated adenoma/polyp (SSA/P) with high confidence utilizing MS
      classification was 93.2%. The differentiation of SSA/P from other lesions
      achieved Sp, Sn, PPV and NPV of 87.2%, 91.5%, 89.6% and 98.6%, respectively. The
      NPV for predicting adenomas in diminutive rectosigmoid polyps (n = 150) was 96.6%
      and 95% with MS and NICE respectively. The calculated accuracy of post
      polypectomy surveillance for MS group was 98.2% (167 out of 170) and for NICE
      group was 92.1% (139 out of 151). CONCLUSION: The MS classification outperformed
      the NICE classification in differentiating neoplastic polyps and predicting
      endoscopic resectability. Both classifications met ASGE PIVI thresholds.

PMID- 30283605
TI  - Successful stent-in-stent dilatation of the common bile duct through a duodenal
      prosthesis, a novel technique for malignant obstruction: A case report and review
      of literature.
AB  - For patients suffering from both biliary and duodenal obstruction, endoscopic
      retrograde cholangiopancreatography (ERCP) with stent placement is the treatment
      of choice. ERCP through an already existing duodenal prosthesis is an uncommon
      procedure and furthermore no studies have reported installing a covered metal
      stent onto an already existing bare metal stent in the common bile duct (CBD). We
      describe a rare case of a stent-in-stent dilatation of the CBD through an already
      existing self-expanding metal stent in the second part of duodenum for the
      patient presenting with jaundice in setting of biliary and duodenal obstruction
      from pancreatic adenocarcinoma. The biliary obstruction was relieved with a
      decrease in bilirubin levels post-stenting.

PMID- 30283607
TI  - Inverted Meckel's diverticulum: Two case reports and a review of the literature.
AB  - Gastrointestinal surgeons seldom encounter inverted Meckel's diverticulum in
      their clinical practice. We describe two cases of inverted Meckel's diverticulum.
      If the patient has a disease-related complication such as intussusception, as
      with our first case, it can be easily detected. However, if the patient has
      subacute or chronic symptoms, as with our second case, the diagnosis might be
      delayed. Regardless of the disease-related complication, intussusception of
      inverted Meckel's diverticulum can be easily managed with laparoscopic single
      port surgery.

PMID- 30283606
TI  - Systematic review of cystic duct closure techniques in relation to prevention of
      bile duct leakage after laparoscopic cholecystectomy.
AB  - AIM: To study the effect of different techniques of cystic duct closure on bile
      leakage after laparoscopic cholecystectomy (LC) for biliary disease. METHODS: A
      systematic search of MEDLINE, Cochrane and EMBASE was performed. Rate of cystic
      duct leakage (CDL) was the primary outcome. Risk of bias was evaluated. Odds
      ratios were analyzed for comparison of techniques and pooled event rates for non
      comparative analyses. Pooled event rates were compared for each of included
      techniques. RESULTS: Out of 1491 articles, 38 studies were included. A total of
      47491 patients were included, of which 38683 (81.5%) underwent cystic duct
      closure with non-locking (metal) clips. All studies were of low-moderate
      methodological quality. Only two studies reported separate data on uncomplicated
      and complicated gallbladder disease. For overall CDL, an odds ratio of 0.4
      (95%CI: 0.06-2.48) was found for harmonic energy vs clip closure and an odds
      ratio of 0.17 (95%CI: 0.03-0.93) for locking vs non-locking clips. Pooled CDL
      rate was around 1% for harmonic energy and metal clips, and 0% for locking clips
      and ligatures. CONCLUSION: Based on available evidence it is not possible to
      either recommend or discourage any of the techniques for cystic duct closure
      during LC with respects to CDL, although data point out a slight preference for
      locking clips and ligatures vs other techniques. No separate recommendation can
      be made for complicated gallbladder disease.

PMID- 30283609
TI  - Readability of Colorectal Cancer Online Information: A Brief Report.
AB  - Purpose: Colorectal cancer (CRC) is the third leading cause of cancer-related
      death in the United States. A decline in deaths caused by CRC has been largely
      attributable to screening and prompt treatment. Motivation, shown to influence
      cancer-related screening and treatment decisions, can be shaped by information
      from the Internet. The extent to which this information is easily readable on
      cancer-related websites is not known. The purpose of this study was to assess the
      readability levels of CRC information on 100 websites. Methods: Using methods
      from a prior study, the keyword, "colorectal cancer," was searched on a cleared
      Internet browser. Scores for each website (n = 100) were generated using five
      commonly recommended readability tests. Results: All five tests demonstrated
      difficult readability for the majority of the websites. Conclusions: Online
      information related to CRC is difficult to read and highlights the need for
      developing cancer-related online material that is understandable to a wider
      audience.

PMID- 30283608
TI  - Treat patient, not just the disease: holistic needs assessment for haematological
      cancer patients.
AB  - Haematological malignancies can have devastating effects on the patients'
      physical, emotional, psycho-sexual, educational and economic health. With the
      improvement of therapies patients with these malignancies are living longer,
      however significant proportion these patient show poor quality of life (QoL) due
      to various physical and psychological consequences of the disease and the
      treatments. Health-related QoL (HRQoL) is multi-dimensional and temporal,
      relating to a state of functional, physical, psychological and social/family well
      being. Compared with the general population, HRQoL of these patients is worse in
      most dimensions. However without routine holistic need assessment (HNA),
      clinicians are unlikely to identify patients with clinically significant
      distress. Surviving cancer is a chronic life-altering condition with several
      factors negatively affecting their QoL, such as psychological problems, including
      depression and excessive fear of recurrence, as well as social aspects, such as
      unemployment and social isolation. These need to be adequately understood and
      addressed in the healthcare of long-term survivors of haematological cancer.
      Applying a holistic approach to patient care has many benefits and yet, only
      around 25% of cancer survivors in the UK receive a holistic needs assessment. The
      efforts of the last decade have established the importance of ensuring access to
      psychosocial services for haematological cancer survivors. We need to determine
      the most effective practices and how best to deliver them across diverse
      settings. Distress, like haematological cancer, is not a single entity, and one
      treatment does not fit all. Psychosocialoncology needs to increase its research
      in comparative effectiveness.

PMID- 30283610
TI  - Pharmacological and Non-pharmacological Means for Prevention of Fractures among
      Elderly.
AB  - Fractures are major cause of morbidity, mortality, and healthcare and social
      services expenditure in elderly. Fractures often have multifactorial etiologies
      and the condition emerges due to the interaction between the different
      predisposing and precipitating factors. One of the most common causes leading to
      fractures after minimal trauma in older people is osteoporosis. The objective of
      this article is to describe the clinical concept and summarize the evidence and
      to explain the future directions for research, focusing on specific issues
      related to prevent fracture in the elderly. This study reviewed the scientific
      literature addressing strategies for primary and secondaryprevention of fractures
      among elderly in the context of pharmacological and non-pharmacological means. A
      growing body of scientific evidence supports the use of both non-pharmacological
      and pharmacological interventions for the prevention of fracture. Research on
      these interventions has yielded positive outcomes in fracture rates. The
      bisphosphonates and vitamin D and calcium suppliments are the preferred therapy
      for prevention of osteoporotic fractures. Weight-bearing exercise and reducing
      home hazards have beneficial effects in reducing the incidence of falls and
      consequently reduce fractures. Prevention of fractures in elderly consists of
      therapy and prevention of osteoporosis, fall prevention, and using injury-site
      protection by high-risk elderly patients. Special consideration needs to be taken
      to reduce home hazard, and falls prevention education can be recommended to the
      elderly with history of fall or mobility limitations. Future research to prevent
      fractures in elderly population should not only concentrate on improving bone
      density and strength but also need to be focused on falls reduction strategies.

PMID- 30283612
TI  - Dietary Supplements and Cardiovascular Diseases.
AB  - The market of nutritional supplements is expected to expand over 6%/year through
      2018 due to growing interest in personal health, aging population, and promising
      personalized care products. The most used dietary supplements are fish oil,
      multivitamins, Vitamin D, and coenzyme Q10 (CoQ10) in this order, while
      probiotics is the fastest growing supplement. In the U.S., over 68% of the
      population use dietary supplements regularly. On the other hand, in the developed
      countries, cardiovascular diseases (CVDs) are the main cause of death and
      morbidity from the 1900s. The effects of most dietary supplements on
      cardiovascular risk and CVD have been studied for a long time. However, despite
      several studies explored the association of the various supplements to the
      cardiovascular risk, there is still a lack of consensus. Multivitamin
      supplementation has been advocated to reduce cardiovascular events; Vitamin D
      levels have been associated with the occurrence of coronary artery disease, heart
      failure, and atrial fibrillation; CoQ10 deficiency has been associated with
      myocardial dysfunction and with statin myopathy; probiotoics has been suggested
      to lower both blood pressure and circulating lipids. However, the study of the
      effects of dietary supplementations is not straightforward, since people assuming
      dietary supplements generally have a healthier diet and lifestyle, and randomized
      studies are rarely performed. In this review, we will summarize the findings
      linking dietary supplements to CVD with a special focus on novel insights.

PMID- 30283613
TI  - Interventions for Physician Burnout: A Systematic Review of Systematic Reviews.
AB  - Occupational burnout is a common syndrome among physicians, and several
      individual-directed and organization-directed interventions have been implemented
      to reduce it. Until now, several review studies have tried to identify and
      introduce the most appropriate interventions. The aim of this article was to
      systematically review systematic review studies of interventions for physician
      burnout to evaluate and summarize their results, and ultimately guide researchers
      to select appropriate interventions. A search was conducted to find review
      studies and systematic reviews in Cochrane Database of Systematic Reviews,
      Medline, Google Scholar, PubMed, and PsycINFO. Two reviewers independently
      selected and evaluated the studies based on inclusion criteria. Four of seven
      obtained review studies and systematic reviews met the inclusion criteria. These
      studies have reviewed individual-directed and organization-directed interventions
      intended to reduce burnout among medical students, interns, physicians,
      residents, and fellows. Various studies of the effectiveness of individual- and
      organization-directed interventions have obtained different results. This
      research has shown that reaching conclusions about effective interventions
      (individual- or organization-directed) for physician burnout is not easy and that
      a number of mediating or moderating variables probably influence the
      effectiveness of these interventions. Therefore, it is necessary to understand
      approaches and interventions for the prevention or reduction of physician burnout
      to fill the gaps in research. In addition, review studies are required to be more
      precise in choosing their criteria to find more accurate results.

PMID- 30283611
TI  - Ocular Parasitosis Caused by Protozoan Infection during Travel: Focus on
      Prevention and Treatment.
AB  - International travel is rising quickly worldwide. Many people travel to tropical
      and subtropical areas, where there has been increasing exposure of travelers to
      infectious pathogens. Ocular parasitic infections are more prevalent in these
      geographical areas and they can lead to morbidity and mortality, often due to
      late or misdiagnosis due to the unfamiliarity of health staff with these
      diseases. This is an up-to-date comprehensive review article that familiarizes
      physicians with ocular signs and symptoms, treatment, prevention, and geographic
      distribution of some parasites associated with travel.

PMID- 30283614
TI  - Effect of Coenzyme Q10 Supplementation on Serum of High Sensitivity c-reactive
      Protein Level in Patients with Cardiovascular Diseases: A Systematic Review and
      Meta-analysis of Randomized Controlled Trials.
AB  - : Possible effects of coenzyme Q10 (CoQ10) supplement on the serum level of high
      sensitivity C-reactive protein (hs-CRP) in cardiovascular diseases (CVDs) remains
      unclear. Objective: Therefore, this meta-analysis was conducted to investigate
      its effects on the serum hs-CRP level in patients with CVDs. A comprehensive
      search was conducted on the EMBASE, MEDLINE, and PubMed Central databases for
      pertinent papers in English up to November 2016. All randomized controlled trials
      (RCTs) that studied the effects of supplementation with CoQ10 on the serum of hs
      CRP level in cardiovascular patients were included. We used random-effects models
      (the DerSimonian-Laird method) to estimate the pooled effect of selected studies
      and the I2 test to assess the between-study heterogeneity. The subgroup analyses
      were carried out according to the baseline serum hs-CRP, quality assessment
      score, supplementation dosage, and duration of intervention. Of 205 studies, five
      trials were eligible for inclusion in this study with 159 participants in the
      ntervention and 143 participants in the placebo group. Results of the pooled
      analysis revealed that the CoQ10 supplementation had no significant effect on the
      serum level of hs-CRP compared with the placebo group (MD: 0.120; 95% = -0.944,
      1.185; P = 0.825). Moreover, the subgroup analyses showed the baseline serum hs
      CRP, quality assessment score, and duration of intervention can be sources of
      heterogeneity. The results of this study demonstrated that the beneficial effect
      of CoQ10 supplementation for patients with CVDs is observed in those who received
      this supplement for more than 12 weeks and with the baseline serum hs-CRP >3
      mg/L.

PMID- 30283616
TI  - Bacteremic meningitis due to Pasteurella multocida resistant to first line
      antibiotic therapy.
AB  - Pasteurella species reside in the gastrointestinal tract of many animals,
      especially in pets such as cats or dogs. Zoonotic transmission of Pasteurella to
      human is documented. We describe a case of meningitis in a 66-year-old woman with
      positive blood culture for Pasteurella multocida. Meningitis caused by zoonosis
      agents is a rare event, but it should be suspected in patients that have
      recreational or professional exposure to animals. In this case, not only the
      etiologic agent was rare, but the microorganism was also resistant to firstline
      antibiotic drugs.

PMID- 30283615
TI  - Comparative Effectiveness of Prophylactic Therapies for Necrotizing Enterocolitis
      in Preterm Infants: Protocol for a Network Meta-analysis of Randomized Trials.
AB  - : Necrotizing enterocolitis (NEC) is a common and devastating disease with high
      morbidity and mortality in premature infants. Current literature on the
      prevention of NEC has limitations including lack of direct and indirect
      comparisons of available therapies. We will search MEDLINE, EMBASE, Science
      Citation Index Expanded, Social Sciences Citation Index, CINAHL, Scopus, ProQuest
      Dissertations and Theses database, and grey literature sources to identify
      eligible trials evaluating NEC preventive therapies. Eligible studies will (1)
      enroll preterm (gestational age <37 weeks) and/or low birth weight (birth weight
      <2500 g) infants, (2) randomize infants to any preventive intervention or a
      placebo, or alternative active or nonactive intervention. Our outcomes of
      interest are severe NEC (stage II or more, based on Bell's criteria), all-cause
      mortality, NEC-related mortality, late-onset sepsis, duration of hospitalization,
      weight gain, time to establish full enteral feeds, and treatment-related adverse
      events. Two reviewers will independently screen trials for eligibility, assess
      risk of bias, and extract data. All discrepancies will be resolved by discussion.
      We will specify a priori explanations for heterogeneity between studies. For
      available comparisons between treatment and no treatment, and direct comparisons
      of treatments, we will conduct conventional meta-analysis using a random effects
      model. We will conduct a network meta-analysis using a random effects model
      within the Bayesian framework using Markov chain Monte Carlo methods to assess
      relative effects of eligible interventions. We will assess the certainty in
      direct, indirect, and network estimates using the Grading of Recommendations
      Assessment, Development and Evaluation approach. Ethics and Dissemination: We
      will disseminate our findings through a peer-reviewed publication and conference
      presentations.

PMID- 30283617
TI  - Acquired hemophilia A developing cerebral infarction 36 days after the frequent
      administration of bypass hemostatic agents.
AB  - A 74-years-old male who was a smoker and received treatment for hypertension,
      dyslipidemia, peripheral arterial disease and idiopathic interstitial pneumonia
      complained of subcutaneous hemorrhage of the right lower thigh. Marked anemia
      (hemoglobin 5.5 g/dL) and prolonged activated partial thromboplastin time (>=130
      seconds) were noted. The factor VIII activity level was reduced to 1.2%, and the
      factor VIII inhibitor titer was 285.3 BU/mL, a diagnosis of acquired hemophilia A
      (AHA) was made. Then, hematomas of 5 intra-muscles were recurred. Hemostasis
      became difficult despite frequent and high-dose administration of recombinant
      human coagulation factor VIIa (total: 18 days, 305 mg). Hemostasis was achieved
      by switching to activated prothrombin complex concentrate (for 3 days, 18,000
      units), however, cerebral infarction occurred after 36 days. After the frequent
      administration of bypass hemostatic agents on elderly AHA patients with several
      risk factors for ischemic stroke, the risk of subsequent thrombotic events may
      persist for 1 month.

PMID- 30283618
TI  - Clinical significance of dasatinib-induced pleural effusion in patients with de
      novo chronic myeloid leukemia.
AB  - Dasatinib is currently approved for clinical use as a first-line treatment agent
      for newly diagnosed chronic myeloid leukemia (CML). However, only a few clinical
      trials have been performed to evaluate dasatinibinduced PE following first-line
      therapy. We investigated the incidence and clinical features of dasatinib-induced
      PE following first-line therapy in Japanese CML patients of real world clinical
      practice settings. Among 22 patients, the median age of PE-positive patients was
      higher than that of PE-negative patients. Major molecular response was achieved
      in 75% of PE-positive patients and 50% of PE-negative patients. Most patients
      developed PE more than 1 year after treatment. Appearance of PE is associated
      with better clinical response during dasatinib treatment, however it is developed
      at any time. Elderly and high-risk patients tend to develop PE. The clinical
      features of dasatinib-induced PE following first-line therapy might be late onset
      and might not immediately follow the increasing of large granular lymphocyte.

PMID- 30283619
TI  - Long-term complete remission of early hematological relapse after discontinuation
      of immunosuppressants following allogeneic transplantation for Sezary syndrome.
AB  - Sezary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma and is chemo
      resistant. Allogeneic hematopoietic stem cell transplantation is a promising
      therapy for SS; however, relapse is common. Therapeutic options after relapse
      have not been established. We managed an SS patient with hematological relapse
      within one month after transplantation. After discontinuation of
      immunosuppressants, she achieved complete remission and remained relapse-free.
      The chimeric analyses of Tcells showed that the full recipient type became
      complete donor chimera after immunological symptoms. This clinical course
      suggested that discontinuation of immunosuppressants may result in a graftversus-
      tumor effect, leading to the eradication of lymphoma cells.

PMID- 30283620
TI  - The role of red cell distribution width in the differential diagnosis of iron
      deficiency anemia and non-transfusiondependent thalassemia patients.
AB  - This study aims to find the cut-off value and diagnostic accuracy of the use of
      RDW as initial investigation in enabling the differentiation between IDA and NTDT
      patients. Patients with microcytic anemia were enrolled in the training set and
      used to plot a receiving operating characteristics (ROC) curve to obtain the cut
      off value of RDW. A second set of patients were included in the validation set
      and used to analyze the diagnostic accuracy. We recruited 94 IDA and 64 NTDT
      patients into the training set. The area under the curve of the ROC in the
      training set was 0.803. The best cut-off value of RDW in the diagnosis of NTDT
      was >21.0% with a sensitivity and specificity of 81.3% and 55.3% respectively. In
      the validation set, there were 34 IDA and 58 NTDT patients using the cut-off
      value of 21.0% to validate. The sensitivity, specificity, positive predictive
      value and negative predictive value were 84.5%, 70.6%, 83.1% and 72.7%
      respectively. We can therefore conclude that RDW >21.0% is useful in
      differentiating between IDA and NTDT patients with high diagnostic accuracy.

PMID- 30283621
TI  - Myelodysplasia-related acute myeloid leukemia and acute promyelocytic leukemia:
      concomitant occurrence of two molecularly distinct diseases.
AB  - Concurrent presentation of acute promyelocytic leukemia (APL) with other
      hematologic diseases in the absence of previous chemotherapy or ionizing
      radiotherapy treatment is very rare. We present a case of simultaneous occurrence
      of APL with myelodysplastic syndrome (MDS)-related acute myeloid leukemia (AML).
      A 43-yearold female presented with 3 month of history fatigue, night sweats,
      chills and pancytopenia. Bone marrow aspirate and biopsy demonstrated 20% myeloid
      blasts with dysplastic changes admixed with abnormal promyelocytes. Cytogenetic
      analysis showed tetraploidy and deletion in chromosomes 5q and 7q and polymerase
      chain reaction showed presence of PML/RARA mRNA transcripts, confirming the
      presence of concurrent APL and MDS-related AML. Induction chemotherapy with
      cytarabine and daunorubicin was initiated along with all-trans retinoic acid.
      This is the first case to be reported in the literature of concurrent occurrence
      of APL with MDS-related AML. Treatment with 7 + 3 regimen and ATRA was successful
      in inducing complete remission.

PMID- 30283622
TI  - The progression of severe aplastic anemia to hypoplastic leukemia in a long-term
      observation after the administration of pegylated rHuMGDF.
AB  - Thrombopoietin (TPO) is a critical regulator of hematopoiesis. We previously
      reported that a severe aplastic anemia (SAA) who received a short-term
      administration of pegylated recombinant human megakaryocyte growth and
      development factor (rHuMGDF). A trilineage hematologic response was induced,
      however the patient was diagnosed with leukemia after nine years and eight months
      from administration of rHuMGDF. In recent reports, somatic mutations in myeloid
      cancer candidate genes were present in one-third of the AA. A mutant clone may be
      expanded by rHuMGDF in our patient. The long-term safety of patients treated with
      TPO and eltrombopag remains unknown. Careful observations are warranted
      hereafter.

PMID- 30283623
TI  - The Illusion of Uniformity Does Not Depend on the Primary Visual Cortex: Evidence
      From Sensory Adaptation.
AB  - Visual experience appears richly detailed despite the poor resolution of the
      majority of the visual field, thanks to foveal-peripheral integration. The
      recently described uniformity illusion (UI), wherein peripheral elements of a
      pattern take on the appearance of foveal elements, may shed light on this
      integration. We examined the basis of UI by generating adaptation to a pattern of
      Gabors suitable for producing UI on orientation. After removing the pattern,
      participants reported the tilt of a single peripheral Gabor. The tilt aftereffect
      followed the physical adapting orientation rather than the global orientation
      perceived under UI, even when the illusion had been reported for a long time.
      Conversely, a control experiment replacing illusory uniformity with a physically
      uniform Gabor pattern for the same durations did produce an aftereffect to the
      global orientation. Results indicate that UI is not associated with changes in
      sensory encoding at V1 but likely depends on higher level processes.

PMID- 30283624
TI  - Scientific evidence, rather than uncontrolled case studies should be the basis
      for patient management.

PMID- 30283625
TI  - Real-world incidence of patient-reported dyspnoea with ticagrelor.
AB  - Dyspnoea, a common and multifactorial symptom in patients with acute coronary
      syndrome, has been associated with lower quality of life and hospital
      readmission. Prescriber preference for antiplatelet therapy, the standard of care
      in this patient group, is shifting to ticagrelor due to mortality benefits
      demonstrated in trials compared with clopidogrel. In these trials, dyspnoea was
      more commonly reported in patients prescribed ticagrelor but the aetiology is
      still debated. An observational cohort study was conducted to quantify the rates
      and severity of dyspnoea reported in patients with acute coronary syndrome and
      newly prescribed ticagrelor compared with those prescribed clopidogrel. Dyspnoea
      was more commonly reported in patients prescribed ticagrelor at each follow up
      post-discharge (p = 0.016). Rates were higher than previously reported in
      clinical trials. In some patients, dyspnoea necessitated drug therapy change and
      was associated with readmission to hospital (p = 0.046). As ticagrelor is widely
      prescribed as a first-line antiplatelet agent for a range of patients with acute
      coronary syndrome, the incidence of dyspnoea in a generalized patient cohort may
      result in higher rates of drug discontinuation. This in turn could lead to higher
      rates of rehospitalisation and potential treatment failure than that reported
      from the controlled setting of a clinical trial.

PMID- 30283626
TI  - Adverse drug reaction reporting in a large tertiary hospital in Saudi Arabia:
      results of an incentive strategy.
AB  - Background: Underreporting is a common problem with spontaneous adverse drug
      reaction (ADR) reporting. In this study, we aim to describe the reporting of ADRs
      in a tertiary hospital and determine the effect of incentives to healthcare
      professionals on ADR reporting. Methods: In this interventional study, a time
      series analysis was used to determine the effect of incentives on ADR reporting
      in a tertiary hospital between 2015 and 2016. The incentive strategy included
      public commendation of health care providers and nomination for a monthly award.
      Results: A total of 967 ADRs were reported over a 2-year period. After the
      introduction of incentives in January 2016, the number of ADR reports per month
      increased by 40.6 (95% confidence interval: 26.1-55.1). The proportion of serious
      ADRs reported was significantly higher in 2016 (39/800) than 2015 (0/167) (p <
      0.001). In 2016, there was a significant association between profession and
      serious ADR reporting (p < 0.001). A total of 14/21 ADRs (66.7%) reported by
      physicians in 2016 were serious compared with 20/700 (2.9%) reported by clinical
      pharmacists and 5/72 (6.9%) by nurses. Conclusions: ADR reporting was improved by
      providing incentives, including commendation and reward, to healthcare
      professionals.

PMID- 30283627
TI  - Using social media in safety signal management: is it reliable?
AB  - Social media use is growing globally, with a reported 3 billion active users in
      2017. This medium is used increasingly in a health setting by patients (and to a
      limited extent, healthcare professionals) to share experiences and ask advice on
      medical conditions as well as pharmaceutical products. In recent years, attention
      has turned to this huge, generally untapped, source of potential health
      information as a possible tool for pharmacovigilance, and in particular signal
      detection. In this article we explore some of the challenges of utilizing social
      media for safety signal detection and look at some of the pilot studies conducted
      to date in order to weigh the evidence for and against the utility of social
      media data in safety signal detection. After doing so we can conclude that the
      analysis of social media datasets has demonstrated a limited contribution to the
      signal detection and signal management process. The data available in social
      media can complement blind spots in traditional pharmacovigilance datasets and
      provide significant value for targeted investigations and studies such as those
      relating to abuse, misuse, use in pregnancy, and patient sentiments.

PMID- 30283628
TI  - The surge in biosimilars: considerations for effective pharmacovigilance and EU
      regulation.
AB  - The development of biosimilars is growing rapidly, especially in Europe. They are
      a cost-effective alternative to original biological medicines and can help
      improve patient access to these therapies. The European Medicines Agency (EMA)
      has been the first to issue scientific guidelines related to regulatory
      requirements for the approval of biosimilars. These guidelines have been being
      updated in line with advances in analytical techniques and growing experience in
      the clinical use of these drugs. Given the complex nature of biological
      medicines, they pose a greater potential risk of immunogenicity than
      nonbiological medicines, and hence warrant special consideration. The risk
      management plan for biopharmaceuticals (innovator and biosimilar drugs) should be
      based on strengthening ongoing pharmacovigilance activities, especially in the
      post-approval period. This paper addresses regulatory issues related to the
      approval of biosimilars in Europe associated with safety considerations linked to
      the development and use of these medicines. We also discuss the issues of
      immunogenicity, interchangeability and traceability of biological medicines.

PMID- 30283629
TI  - Diagnosing microscopic pancreatic neuroendocrine tumor using 68-Ga-DOTATATE
      PET/CT: case series.
AB  - Neuroendocrine tumors (NETs) are an uncommon diagnosis which often present
      asymptomatically or with vague symptoms. They can originate from many different
      organs such as the GI tract, lungs, pancreas and others. 68Gallium DOTATATE
      positron emission topography/computed topography has been shown to be an
      effective imaging modality for diagnosing NET and evaluating management options
      for patients. Here, we present two cases of positive findings in the distal
      pancreas on the DOTATATE PET/CT scans without any morphological lesion found to
      be NET in a healthy 48-year-old male and 68-year-old male.

PMID- 30283630
TI  - Adult ileocecal intussusception induced by adenomatous ileal polyp: case report
      and literature review.
AB  - Intussusception is a rare cause of bowel obstruction in adults, and has generally
      an organic etiology. However, adenomatous polyp of the small bowel is an uncommon
      etiology. Moreover, there's a great difference with childhood intussusception in
      its presentation, etiology and management. We describe herein a case of adult
      ileocecal intussusception due to an adenomatous ileal polyp with a preoperative
      diagnosis made on computed tomography. We performed a right hemicolectomy,
      without attempting to reduce the intussusception, and an end-to-end
      ileotransverse anastomosis. The pathological examination of the surgical specimen
      revealed an adenomatous polyp with a high grade dysplasia on the terminal ileum,
      being the cause of the ileocecal intussusception.

PMID- 30283631
TI  - Biliary obstruction secondary to migrated intra-duodenal gastric band: a case
      report.
AB  - Adjustable gastric banding (AGB) was a previously popular bariatric procedure,
      but adverse events such as erosion have surfaced as common complications. We
      present an interesting case of an AGB causing biliary obstruction after eroding
      into the stomach.

PMID- 30283632
TI  - Elastic serum-albumin based hydrogels: mechanism of formation and application in
      cardiac tissue engineering.
AB  - Hydrogels are promising materials for mimicking the extra-cellular environment.
      Here, we present a simple methodology for the formation of a free-standing
      viscoelastic hydrogel from the abundant and low cost protein serum albumin. We
      show that the mechanical properties of the hydrogel exhibit a complicated
      behaviour as a function of the weight fraction of the protein component. We
      further use X-ray scattering to shed light on the mechanism of gelation from the
      formation of a fibrillary network at low weight fractions to interconnected
      aggregates at higher weight fractions. Given the match between our hydrogel
      elasticity and that of the myocardium, we investigated its potential for
      supporting cardiac cells in vitro. Interestingly, these hydrogels support the
      formation of several layers of myocytes and significantly promote the maintenance
      of a native-like gene expression profile compared to those cultured on glass.
      When confronted with a multicellular ventricular cell preparation, the hydrogels
      can support macroscopically contracting cardiac-like tissues with a distinct cell
      arrangement, and form mm-long vascular-like structures. We envisage that our
      simple approach for the formation of an elastic substrate from an abundant
      protein makes the hydrogel a compelling biomedical material candidate for a wide
      range of cell types.

PMID- 30283634
TI  - Introducing Evolution Letters.

PMID- 30283635
TI  - Sperm storage by males causes changes in sperm phenotype and influences the
      reproductive fitness of males and their sons.
AB  - Recent studies suggest that environmentally induced effects on sperm phenotype
      can influence offspring phenotype beyond the classic Mendelian inheritance
      mechanism. However, establishing whether such effects are conveyed purely through
      ejaculates, independently of maternal environmental effects, remains a
      significant challenge. Here, we assess whether environmentally induced effects on
      sperm phenotype affects male reproductive success and offspring fitness. We
      experimentally manipulated the duration of sperm storage by males, and thus sperm
      age, in the internally fertilizing fish Poecilia reticulata. We first confirm
      that sperm ageing influences sperm quality and consequently males reproductive
      success. Specifically, we show that aged sperm exhibit impaired velocity and are
      competitively inferior to fresh sperm when ejaculates compete to fertilize eggs.
      We then used homospermic (noncompetitive) artificial insemination to inseminate
      females with old or fresh sperm and found that male offspring arising from
      fertilizations by experimentally aged sperm suffered consistently impaired sperm
      quality when just sexually mature (four months old) and subsequently as adults
      (13 months old). Although we have yet to determine whether these effects have a
      genetic or epigenetic basis, our analyses provide evidence that environmentally
      induced variation in sperm phenotype constitutes an important source of variation
      in male reproductive fitness that has far reaching implications for offspring
      fitness.

PMID- 30283633
TI  - The importance of clinical pharmacokinetic-pharmacodynamic studies in unraveling
      the determinants of early and late tuberculosis outcomes.
AB  - Tuberculosis remains a major infectious cause of morbidity and mortality
      worldwide. Current antibiotic regimens, constructed prior to the development of
      modern pharmacokinetic-pharmacodynamic (PK-PD) tools, are based on incomplete
      understanding of exposure-response relationships in drug susceptible and
      multidrug resistant tuberculosis. Preclinical and population PK data suggest that
      clinical PK-PD studies may enable therapeutic drug monitoring for some agents and
      revised dosing for others. Future clinical PK-PD challenges include:
      incorporation of PK methods to assay free concentrations for all active
      metabolites; selection of appropriate early outcome measures which reflect
      therapeutic response; elucidation of genetic contributors to interindividual PK
      variability; conduct of targeted studies on special populations (including
      children); and measurement of PK-PD parameters at the site of disease.

PMID- 30283636
TI  - Integrating viability and fecundity selection to illuminate the adaptive nature
      of genetic clines.
AB  - Genetically based trait variation across environmental gradients can reflect
      adaptation to local environments. However, natural populations that appear well
      adapted often exhibit directional, not stabilizing, selection on ecologically
      relevant traits. Temporal variation in the direction of selection could lead to
      stabilizing selection across multiple episodes of selection, which might be
      overlooked in short-term studies that evaluate relationships of traits and
      fitness under only one set of conditions. Furthermore, nonrandom mortality prior
      to trait expression can bias inferences about trait evolution if viability
      selection opposes fecundity selection. Here, we leveraged fitness and trait data
      to test whether phenotypic clines are genetically based and adaptive, whether
      temporal variation in climate imposes stabilizing selection, and whether
      viability selection acts on adult phenotypes. We monitored transplants of the
      subalpine perennial forb, Boechera stricta (Brassicaceae), in common gardens at
      two elevations over 2-3 years that differed in drought intensity. We quantified
      viability, and fecundity fitness components for four heritable traits: specific
      leaf area, integrated water-use efficiency, height at first flower, and flowering
      phenology. Our results indicate that genetic clines are maintained by selection,
      but their expression is context dependent, as they do not emerge in all
      environments. Moreover, selection varied spatially and temporally. Stabilizing
      selection was most pronounced when we integrated data across years. Finally,
      viability selection prior to trait expression targeted adult phenotypes (age and
      size at flowering). Indeed, viability selection for delayed flowering opposed
      fecundity selection for accelerated flowering; this result demonstrates that
      neglecting to account for viability selection could lead to inaccurate
      conclusions that populations are maladapted. Our results suggest that reconciling
      clinal trait variation with selection requires data collected across multiple
      spatial scales, time frames, and life-history stages.

PMID- 30283637
TI  - Linking speciation to extinction: Diversification raises contemporary extinction
      risk in amphibians.
AB  - Many of the traits associated with elevated rates of speciation, including niche
      specialization and having small and isolated populations, are similarly linked
      with an elevated risk of extinction. This suggests that rapidly speciating
      lineages may also be more extinction prone. Empirical tests of a speciation
      extinction correlation are rare because assessing paleontological extinction
      rates is difficult. However, the modern biodiversity crisis allows us to observe
      patterns of extinction in real time, and if this hypothesis is true then we would
      expect young clades that have recently diversified to have high contemporary
      extinction risk. Here, we examine evolutionary patterns of modern extinction risk
      across over 300 genera within one of the most threatened vertebrate classes, the
      Amphibia. Consistent with predictions, rapidly diversifying amphibian clades also
      had a greater share of threatened species. Curiously, this pattern is not
      reflected in other tetrapod classes and may reflect a greater propensity to
      speciate through peripheral isolation in amphibians, which is partly supported by
      a negative correlation between diversification rate and mean geographic range
      size. This clustered threat in rapidly diversifying amphibian genera means that
      protecting a small number of species can achieve large gains in preserving
      amphibian phylogenetic diversity. Nonindependence between speciation and
      extinction rates has many consequences for patterns of biodiversity and how we
      may choose to conserve it.

PMID- 30283638
TI  - The coadaptation theory for genomic imprinting.
AB  - Imprinted genes are peculiar in that expression of the two copies differs
      depending on whether the copy was maternally or paternally inherited. The
      discovery of this striking pattern of gene expression inspired myriad
      evolutionary theories, the most successful of which identify scenarios that
      create an asymmetry between the maternally and paternally inherited gene copies
      that favors silencing of one of the copies. Most notably, imprinting can evolve
      when gene dosage affects kin interactions (typically involving conflict) or when
      silencing enhances coadaptation by coordinating traits expressed by interacting
      kin. Although we have a well-established theory for the former process (the
      "Kinship Theory"), the coadaptation process has only been explored for the
      specific case of interactions between mothers and offspring. Here, we fill this
      critical gap in our understanding by developing a general "Coadaptation Theory"
      that explains how imprinting can evolve to coordinate interactions between all
      types of relatives. Using a simple model in which fitness of an individual is
      determined by an interaction between its own phenotype (and hence genotype) and
      that of its social partner(s), we find that when the relatedness of interactants
      differs through their maternally versus paternally inherited gene copies, then
      selection favors expression of the allele through which relatedness is higher.
      The predictions of this Coadaptation Theory potentially apply whenever a gene
      underlies traits that mediate the outcome of conspecific interactions, regardless
      of their mechanism or the type of organism, and therefore provide a potential
      explanation for enigmatic patterns of imprinting, including those underlying
      adult traits. By providing simple testable predictions that often directly
      contrast with those derived from alternative theories, our model should play an
      important role in consolidating our understanding of the evolution of imprinting
      across genes and species, which will ultimately provide crucial insights into
      imprinted gene function and dysfunction.

PMID- 30283639
TI  - Unconscious selection drove seed enlargement in vegetable crops.
AB  - Domesticated grain crops evolved from wild plants under human cultivation, losing
      natural dispersal mechanisms to become dependent upon humans, and showing changes
      in a suite of other traits, including increasing seed size. There is tendency for
      seed enlargement during domestication to be viewed as the result of deliberate
      selection for large seeds by early farmers. However, like some other
      domestication traits, large seeds may have evolved through natural selection from
      the activities of people as they gathered plants from the wild, or brought them
      into cultivation in anthropogenic settings. Alternatively, larger seeds could
      have arisen via pleiotropic effects or genetic linkage, without foresight from
      early farmers, and driven by selection that acted on other organs or favored
      larger plants. We have separated these unconscious selection effects on seed
      enlargement from those of deliberate selection, by comparing the wild and
      domesticated forms of vegetable crops. Vegetables are propagated by planting
      seeds, cuttings, or tubers, but harvested for their edible leaves, stems, or
      roots, so that seed size is not a direct determinant of yield. We find that
      landrace varieties of seven vegetable crops have seeds that are 20% to 2.5-times
      larger than those of their closest wild relatives. These domestication effect
      sizes fall completely within the equivalent range of 14% to 15.2-times for grain
      crops, although domestication had a significantly larger overall effect in grain
      than vegetable crops. Seed enlargement in vegetable crops that are propagated
      vegetatively must arise from natural selection for larger seeds on the occasions
      when plants recruit from seed and are integrated into the crop gene pool, or via
      a genetic link to selection for larger plants or organs. If similar mechanisms
      operate across all species, then unconscious selection during domestication could
      have exerted stronger effects on the seed size of our staple crops than
      previously realized.

PMID- 30283641
TI  - Direct estimation of the spontaneous mutation rate by short-term mutation
      accumulation lines in Chironomus riparius.
AB  - Mutations are the ultimate basis of evolution, yet their occurrence rate is known
      only for few species. We directly estimated the spontaneous mutation rate and the
      mutational spectrum in the nonbiting midge C. riparius with a new approach.
      Individuals from ten mutation accumulation lines over five generations were deep
      genome sequenced to count de novo mutations that were not present in a pool of F1
      individuals, representing parental genotypes. We identified 51 new single site
      mutations of which 25 were insertions or deletions and 26 single nucleotide
      mutations. This shift in the mutational spectrum compared to other organisms was
      explained by the high A/T content of the species. We estimated a haploid mutation
      rate of 2.1 * 10-9 (95% confidence interval: 1.4 * 10-9 - 3.1 * 10-9) that is in
      the range of recent estimates for other insects and supports the drift barrier
      hypothesis. We show that accurate mutation rate estimation from a high number of
      observed mutations is feasible with moderate effort even for nonmodel species.

PMID- 30283640
TI  - A nonrandom subset of olfactory genes is associated with host preference in the
      fruit fly Drosophila orena.
AB  - Specialization onto different host plants has been hypothesized to be a major
      driver of diversification in insects, and traits controlling olfaction have been
      shown to play a fundamental role in host preferences. A diverse set of olfactory
      genes control olfactory traits in insects, and it remains unclear whether
      specialization onto different hosts is likely to involve a nonrandom subset of
      these genes. Here, we test the role of olfactory genes in a novel case of
      specialization in Drosophila orena. We report the first population-level sample
      of D. orena on the West African island of Bioko, since its initial collection in
      Cameroon in 1975, and use field experiments and behavioral assays to show that D.
      orena has evolved a strong preference for waterberry (Syzygium staudtii). We then
      show that a nonrandom subset of genes controlling olfaction--those controlling
      odorant-binding and chemosensory proteins--have an enriched signature of positive
      selection relative to the rest of the D. orena genome. By comparing signatures of
      positive selection on olfactory genes between D. orena and its sister species, D.
      erecta we show that odorant-binding and chemosensory have evidence of positive
      selection in both species; however, overlap in the specific genes with evidence
      of selection in these two classes is not greater than expected by chance.
      Finally, we use quantitative complementation tests to confirm a role for seven
      olfactory loci in D. orena's preference for waterberry fruit. Together, our
      results suggest that D. orena and D. erecta have specialized onto different host
      plants through convergent evolution at the level of olfactory gene family, but
      not at specific olfactory genes.

PMID- 30283642
TI  - A genomic footprint of hybrid zone movement in crested newts.
AB  - Speciation typically involves a stage in which species can still exchange genetic
      material. Interspecific gene flow is facilitated by the hybrid zones that such
      species establish upon secondary contact. If one member of a hybridizing species
      pair displaces the other, their hybrid zone would move across the landscape.
      Although theory predicts that moving hybrid zones quickly stagnate, hybrid zones
      tracked over one or a few decades do not always follow such a limitation. This
      suggests that hybrid zones have the potential to traverse considerable distances
      over extended periods of time. When hybrid zones move, introgression is predicted
      to result in biased gene flow of selectively neutral alleles, from the receding
      species into the advancing species. We test for such a genomic footprint of
      hybrid zone movement in a pair of crested newt species (genus Triturus) for which
      we have a priori support for westward hybrid zone movement. We perform a
      multilocus phylogeographical survey and conduct Bayesian clustering analysis,
      estimation of ancestry and heterozygosity, and geographical cline analysis. In a
      600 km wide area east of the present day hybrid zone a genomic footprint
      constitutes empirical evidence consistent with westward hybrid zone movement. The
      crested newt case suggests that hybrid zone movement can occur over an extensive
      span of time and space. Inferring hybrid zone movement provides fundamental
      insight into historical biogeography and the speciation process, and we
      anticipate that hybrid zones will prove to be far more mobile than currently
      appreciated.

PMID- 30283643
TI  - Experimental evolution reveals that sperm competition intensity selects for
      longer, more costly sperm.
AB  - It is the differences between sperm and eggs that fundamentally underpin the
      differences between the sexes within reproduction. For males, it is theorized
      that widespread sperm competition leads to selection for investment in sperm
      numbers, achieved by minimizing sperm size within limited resources for
      spermatogenesis in the testis. Here, we empirically examine how sperm competition
      shapes sperm size, after more than 77 generations of experimental selection of
      replicate lines under either high or low sperm competition intensities in the
      promiscuous flour beetle Tribolium castaneum. After this experimental evolution,
      populations had diverged significantly in their sperm competitiveness, with sperm
      in ejaculates from males evolving under high sperm competition intensities
      gaining 20% greater paternity than sperm in ejaculates from males that had
      evolved under low sperm competition intensity. Males did not change their
      relative investment into sperm production following this experimental evolution,
      showing no difference in testis sizes between high and low intensity regimes.
      However, the more competitive males from high sperm competition intensity regimes
      had evolved significantly longer sperm and, across six independently selected
      lines, there was a significant association between the degree of divergence in
      sperm length and average sperm competitiveness. To determine whether such sperm
      elongation is costly, we used dietary restriction experiments, and revealed that
      protein-restricted males produced significantly shorter sperm. Our findings
      therefore demonstrate that sperm competition intensity can exert positive
      directional selection on sperm size, despite this being a costly reproductive
      trait.

PMID- 30283644
TI  - No evidence that kin selection increases the honesty of begging signals in birds.
AB  - Providing plausible mechanisms to explain variation in the honesty of information
      communicated through offspring begging signals is fundamental to our
      understanding of parent-offspring conflict and the evolution of family life. A
      recently published research article used comparative analyses to investigate two
      long-standing hypotheses that may explain the evolution of begging behavior. The
      results suggested that direct competition between offspring for parental
      resources decreases begging honesty, whereas indirect, kin-selected benefits
      gained through saving parental resources for the production of future siblings
      increase begging honesty. However, we feel that evidence for a role of kin
      selection in this context is still missing. We present a combination of arguments
      and empirical tests to outline alternative sources of interspecific variation in
      offspring begging levels and discuss avenues for further research that can bring
      us closer to a complete understanding of the evolution of offspring signaling.

PMID- 30283646
TI  - Genetic differences between willow warbler migratory phenotypes are few and
      cluster in large haplotype blocks.
AB  - It is well established that differences in migratory behavior between populations
      of songbirds have a genetic basis but the actual genes underlying these traits
      remains largely unknown. In an attempt to identify such candidate genes we de
      novo assembled the genome of the willow warbler Phylloscopus trochilus, and used
      whole-genome resequencing and a SNP array to associate genomic variation with
      migratory phenotypes across two migratory divides around the Baltic Sea that
      separate SW migrating P. t. trochilus wintering in western Africa and SSE
      migrating P. t. acredula wintering in eastern and southern Africa. We found that
      the genomes of the two migratory phenotypes lack clear differences except for
      three highly differentiated regions located on chromosomes 1, 3, and 5
      (containing 146, 135, and 53 genes, respectively). Within each migratory
      phenotype we found virtually no differences in allele frequencies for thousands
      of SNPs, even when comparing geographically distant populations breeding in
      Scandinavia and Far East Russia (>6000 km). In each of the three differentiated
      regions, multidimensional scaling-based clustering of SNP genotypes from more
      than 1100 individuals demonstrates the presence of distinct haplotype clusters
      that are associated with each migratory phenotype. In turn, this suggests that
      recombination is absent or rare between haplotypes, which could be explained by
      inversion polymorphisms. Whereas SNP alleles on chromosome 3 correlate with
      breeding altitude and latitude, the allele distribution within the regions on
      chromosomes 1 and 5 perfectly matches the geographical distribution of the
      migratory phenotypes. The most differentiated 10 kb windows and missense
      mutations within these differentiated regions are associated with genes involved
      in fatty acid synthesis, possibly representing physiological adaptations to the
      different migratory strategies. The ~200 genes in these regions, of which several
      lack described function, will direct future experimental and comparative studies
      in the search for genes that underlie important migratory traits.

PMID- 30283645
TI  - No evidence for maintenance of a sympatric Heliconius species barrier by
      chromosomal inversions.
AB  - Mechanisms that suppress recombination are known to help maintain species
      barriers by preventing the breakup of coadapted gene combinations. The sympatric
      butterfly species Heliconius melpomene and Heliconius cydno are separated by many
      strong barriers, but the species still hybridize infrequently in the wild, and
      around 40% of the genome is influenced by introgression. We tested the hypothesis
      that genetic barriers between the species are maintained by inversions or other
      mechanisms that reduce between-species recombination rate. We constructed fine
      scale recombination maps for Panamanian populations of both species and their
      hybrids to directly measure recombination rate within and between species, and
      generated long sequence reads to detect inversions. We find no evidence for a
      systematic reduction in recombination rates in F1 hybrids, and also no evidence
      for inversions longer than 50 kb that might be involved in generating or
      maintaining species barriers. This suggests that mechanisms leading to global or
      local reduction in recombination do not play a significant role in the
      maintenance of species barriers between H. melpomene and H. cydno.

PMID- 30283647
TI  - Heterogeneous gene duplications can be adaptive because they permanently
      associate overdominant alleles.
AB  - Gene duplications are widespread in genomes, but their role in contemporary
      adaptation is not fully understood. Although mostly deleterious, homogeneous
      duplications that associate identical repeats of a locus often increase the
      quantity of protein produced, which can be selected in certain environments.
      However, another type exists: heterogeneous gene duplications, which permanently
      associate two (or more) alleles of a single locus on the same chromosome. They
      are far less studied, as only few examples of contemporary heterogeneous
      duplications are known. Haldane proposed in 1954 that they could be adaptive in
      situations of heterozygote advantage, or overdominance, but this hypothesis was
      never tested. To assess its validity, we took advantage of the well-known model
      of insecticide resistance in mosquitoes. We used experimental evolution to
      estimate the fitnesses associated with homozygous and heterozygous genotypes in
      different selection regimes. It first showed that balanced antagonist selective
      pressures frequently induce overdominance, generating stable polymorphic
      equilibriums. The frequency of equilibrium moreover depends on the magnitude of
      two antagonistic selective pressures, the survival advantage conferred by the
      resistant allele versus the selective costs it induces. We then showed that
      heterogeneous duplications are selected over single-copy alleles in such
      contexts. They allow the fixation of the heterozygote phenotype, providing an
      alternative and stable intermediate fitness trade-off. By allowing the rapid
      fixation of divergent alleles, this immediate advantage could contribute to the
      rarity of overdominance. More importantly, it also creates new material for long
      term genetic innovation, making a crucial but underestimated contribution to the
      evolution of new genes and gene families.

PMID- 30283648
TI  - The genomic basis of cichlid fish adaptation within the deepwater "twilight zone"
      of Lake Malawi.
AB  - Deepwater environments are characterized by low levels of available light at
      narrow spectra, great hydrostatic pressure, and low levels of dissolved oxygen
      conditions predicted to exert highly specific selection pressures. In Lake Malawi
      over 800 cichlid species have evolved, and this adaptive radiation extends into
      the "twilight zone" below 50 m. We use population-level RAD-seq data to
      investigate whether four endemic deepwater species (Diplotaxodon spp.) have
      experienced divergent selection within this environment. We identify candidate
      genes including regulators of photoreceptor function, photopigments, lens
      morphology, and haemoglobin, many not previously implicated in cichlid adaptive
      radiations. Colocalization of functionally linked genes suggests coadapted
      "supergene" complexes. Comparisons of Diplotaxodon to the broader Lake Malawi
      radiation using genome resequencing data revealed functional substitutions and
      signatures of positive selection in candidate genes. Our data provide unique
      insights into genomic adaptation within deepwater habitats, and suggest genome
      level specialization for life at depth as an important process in cichlid
      radiation.

PMID- 30283649
TI  - Fire ant social chromosomes: Differences in number, sequence and expression of
      odorant binding proteins.
AB  - Variation in social behavior is common yet our knowledge of the mechanisms
      underpinning its evolution is limited. The fire ant Solenopsis invicta provides a
      textbook example of a Mendelian element controlling social organization:
      alternate alleles of a genetic element first identified as encoding an odorant
      binding protein (OBP) named Gp-9 determine whether a colony accepts one or
      multiple queens. The potential roles of such a protein in perceiving olfactory
      cues and evidence of positive selection on its amino acid sequence made it an
      appealing candidate gene. However, we recently showed that recombination is
      suppressed between Gp-9 and hundreds of other genes as part of a >19 Mb supergene
      like region carried by a pair of social chromosomes. This finding raises the need
      to reassess the potential role of Gp-9. We identify 23 OBPs in the fire ant
      genome assembly, including nine located in the region of suppressed recombination
      with Gp-9. For six of these, the alleles carried by the two variants of the
      supergene-like region differ in protein-coding sequence and thus likely in
      function, with Gp-9 showing the strongest evidence of positive selection. We
      identify an additional OBP specific to the Sb variant of the region. Finally, we
      find that 14 OBPs are differentially expressed between single- and multiple-queen
      colonies. These results are consistent with multiple OBPs playing a role in
      determining social structure.

PMID- 30283651
TI  - Divergent artificial selection for female reproductive investment has a sexually
      concordant effect on male reproductive success.
AB  - Depending on the genetic architecture of male and female fitness, sex-specific
      selection can have negative, positive, or neutral consequences for the opposite
      sex. Theory predicts that conflict between male and female function may drive the
      breakdown of intrasexual genetic correlations, allowing sexual dimorphism in
      sexually antagonistic traits. Reproductive traits are the epitome of this,
      showing highly differentiated proximate functions between the sexes. Here we use
      divergent artificial selection lines for female reproductive investment to test
      how female-specific selection on a sex-limited trait affects male reproductive
      success in a precocial bird, the Japanese quail (Coturnix japonica). We
      demonstrate that selection for increased egg investment in females positively
      affects male reproductive success both in competitive and non-competitive mating
      situations. This increased reproductive success was linked to a relatively larger
      left testis in males originating from lines selected for high female reproductive
      investment. Given that female quail have functional gonads only on their left
      side, this correlated response indicates that selection has acted on the shared
      developmental basis of male and female gonads. Our study thereby provides
      evidence for a positive genetic correlation between key reproductive traits in
      males and females despite a high degree of sexual dimorphism, and suggests that,
      in this system, selection on reproductive function is sexually concordant.

PMID- 30283650
TI  - Friendly foes: The evolution of host protection by a parasite.
AB  - Hosts are often infected by multiple parasite species, yet the ecological and
      evolutionary implications of the interactions between hosts and coinfecting
      parasites are largely unknown. Most theoretical models of evolution among
      coinfecting parasites focus on the evolution of virulence, but parasites may also
      evolve to protect their hosts by reducing susceptibility (i.e., conferring
      resistance) to other parasites or reducing the virulence of coinfecting parasites
      (i.e., conferring tolerance). Here, we analyze the eco-evolutionary dynamics of
      parasite-conferred resistance and tolerance using coinfection models. We show
      that both parasite-conferred resistance and tolerance can evolve for a wide range
      of underlying trade-offs. The shape and strength of the trade-off qualitatively
      affects the outcome causing shifts between the minimisation or maximization of
      protection, intermediate stable strategies, evolutionary branching, and
      bistability. Furthermore, we find that a protected dimorphism can readily evolve
      for parasite-conferred resistance, but find no evidence of evolutionary branching
      for parasite-conferred tolerance, in general agreement with previous work on host
      evolution. These results provide novel insights into the evolution of parasite
      conferred resistance and tolerance, and suggest clues to the underlying trade
      offs in recent experimental work on microbe-mediated protection. More generally,
      our results highlight the context dependence of host-parasite relationships in
      complex communities.

PMID- 30283652
TI  - Feminizing Wolbachia endosymbiont disrupts maternal sex chromosome inheritance in
      a butterfly species.
AB  - Wolbachia is a maternally inherited ubiquitous endosymbiotic bacterium of
      arthropods that displays a diverse repertoire of host reproductive manipulations.
      For the first time, we demonstrate that Wolbachia manipulates sex chromosome
      inheritance in a sexually reproducing insect. Eurema mandarina butterfly females
      on Tanegashima Island, Japan, are infected with the wFem Wolbachia strain and
      produce all-female offspring, while antibiotic treatment results in male
      offspring. Fluorescence in situ hybridization (FISH) revealed that wFem-positive
      and wFem-negative females have Z0 and WZ sex chromosome sets, respectively,
      demonstrating the predicted absence of the W chromosome in wFem-infected
      lineages. Genomic quantitative polymerase chain reaction (qPCR) analysis showed
      that wFem-positive females lay only Z0 eggs that carry a paternal Z, whereas
      females from lineages that are naturally wFem-negative lay both WZ and ZZ eggs.
      In contrast, antibiotic treatment of adult wFem females resulted in the
      production of Z0 and ZZ eggs, suggesting that this Wolbachia strain can disrupt
      the maternal inheritance of Z chromosomes. Moreover, most male offspring produced
      by antibiotic-treated wFem females had a ZZ karyotype, implying reduced survival
      of Z0 individuals in the absence of feminizing effects of Wolbachia. Antibiotic
      treatment of wFem-infected larvae induced male-specific splicing of the doublesex
      (dsx) gene transcript, causing an intersex phenotype. Thus, the absence of the
      female-determining W chromosome in Z0 individuals is functionally compensated by
      Wolbachia-mediated conversion of sex determination. We discuss how Wolbachia may
      manipulate the host chromosome inheritance and that Wolbachia may have acquired
      this coordinated dual mode of reproductive manipulation first by the evolution of
      female-determining function and then cytoplasmically induced disruption of sex
      chromosome inheritance.

PMID- 30283653
TI  - Environmental variation causes different (co) evolutionary routes to the same
      adaptive destination across parasite populations.
AB  - Epidemics are engines for host-parasite coevolution, where parasite adaptation to
      hosts drives reciprocal adaptation in host populations. A key challenge is to
      understand whether parasite adaptation and any underlying evolution and
      coevolution is repeatable across ecologically realistic populations that
      experience different environmental conditions, or if each population follows a
      completely unique evolutionary path. We established twenty replicate pond
      populations comprising an identical suite of genotypes of crustacean host,
      Daphnia magna, and inoculum of their parasite, Pasteuria ramosa. Using a time
      shift experiment, we compared parasite infection traits before and after
      epidemics and linked patterns of parasite evolution with shifts in host genotype
      frequencies. Parasite adaptation to the sympatric suite of host genotypes came at
      a cost of poorer performance on foreign genotypes across populations and
      environments. However, this consistent pattern of parasite adaptation was driven
      by different types of frequency-dependent selection that was contingent on an
      ecologically relevant environmental treatment (whether or not there was physical
      mixing of water within ponds). In unmixed ponds, large epidemics drove rapid and
      strong host-parasite coevolution. In mixed ponds, epidemics were smaller and host
      evolution was driven mainly by the mixing treatment itself; here, host evolution
      and parasite evolution were clear, but coevolution was absent. Population mixing
      breaks an otherwise robust coevolutionary cycle. These findings advance our
      understanding of the repeatability of (co)evolution across noisy, ecologically
      realistic populations.

PMID- 30283655
TI  - Real-time social selection maintains honesty of a dynamic visual signal in
      cooperative fish.
AB  - Our understanding of animal communication has been largely driven by advances in
      theory since empirical evidence has been difficult to obtain. Costly signaling
      theory became the dominant paradigm explaining the evolution of honest signals,
      according to which communication reliability relies on differential costs imposed
      on signalers to distinguish animals of different quality. On the other hand,
      mathematical models disagree on the source of costs at the communication
      equilibrium. Here, we present an empirical framework to study the evolution of
      honest signals that generates predictions on the form, function, and sources of
      reliability of visual signals. We test these predictions on the facial color
      patterns of the cooperatively breeding Princess of Burundi cichlid,
      Neolamprologus brichardi. Using theoretical visual models and behavioral
      experiments we show that these patterns possess stable chromatic properties for
      efficient transmission in the aquatic environment, while dynamic changes in
      signal luminance are used by the fish to communicate switches in aggressive
      intent. By manipulating signal into out-of-equilibrium expression and simulating
      a cheater invasion, we demonstrate that social costs (receiver retaliation)
      promote the honesty of this dynamic conventional signal. By directly probing the
      sender of a signal in real time, social selection is likely to be the mechanism
      of choice shaping the evolution of inexpensive, yet reliable context-dependent
      social signals in general.

PMID- 30283654
TI  - Inconsistent reproductive isolation revealed by interactions between Catostomus
      fish species.
AB  - Interactions between species are central to evolution and ecology, but we do not
      know enough about how outcomes of interactions between species vary across
      geographic locations, in heterogeneous environments, or over time. Ecological
      dimensions of interactions between species are known to vary, but evolutionary
      interactions such as the establishment and maintenance of reproductive isolation
      are often assumed to be consistent across instances of an interaction between
      species. Hybridization among Catostomus fish species occurs over a large and
      heterogeneous geographic area and across taxa with distinct evolutionary
      histories, which allows us to assess consistency in species interactions. We
      analyzed hybridization among six Catostomus species across the Upper Colorado
      River basin (US mountain west) and found extreme variation in hybridization
      across locations. Different hybrid crosses were present in different locations,
      despite similar species assemblages. Within hybrid crosses, hybridization varied
      from only first generation hybrids to extensive hybridization with backcrossing.
      Variation in hybridization outcomes might result from uneven fitness of hybrids
      across locations, polymorphism in genetic incompatibilities, chance, unidentified
      historical contingencies, or some combination thereof. Our results suggest
      caution in assuming that one or a few instances of hybridization represent all
      interactions between the focal species, as species interactions vary
      substantially across locations.

PMID- 30283656
TI  - Single-gene speciation: Mating and gene flow between mirror-image snails.
AB  - Variation in the shell coiling, or chirality, of land snails provides an
      opportunity to investigate the potential for "single-gene" speciation, because
      mating between individuals of opposite chirality is believed not possible if the
      snails mate in a face-to-face position. However, the evidence in support of
      single-gene speciation is sparse, mostly based upon single-gene mitochondrial
      studies and patterns of chiral variation between species. Previously, we used a
      theoretical model to show that as the chiral phenotype of offspring is determined
      by the maternal genotype, occasional chiral reversals may take place and enable
      gene flow between mirror image morphs, preventing speciation. Here, we show
      empirically that there is recent or ongoing gene flow between the different
      chiral types of Japanese Euhadra species. We also report evidence of mating
      between mirror-image morphs, directly showing the potential for gene flow. Thus,
      theoretical models are suggestive of gene flow between oppositely coiled snails,
      and our empirical study shows that they can mate and that there is gene flow in
      Euhadra. More than a single gene is required before chiral variation in shell
      coiling can be considered to have created a new species.

PMID- 30283657
TI  - Mitogenome evolution in the last surviving woolly mammoth population reveals
      neutral and functional consequences of small population size.
AB  - The onset of the Holocene was associated with a global temperature increase,
      which led to a rise in sea levels and isolation of the last surviving population
      of woolly mammoths on Wrangel Island. Understanding what happened with the
      population's genetic diversity at the time of the isolation and during the
      ensuing 6000 years can help clarify the effects of bottlenecks and subsequent
      limited population sizes in species approaching extinction. Previous genetic
      studies have highlighted questions about how the Holocene Wrangel population was
      established and how the isolation event affected genetic diversity. Here, we
      generated high-quality mitogenomes from 21 radiocarbon-dated woolly mammoths to
      compare the ancestral large and genetically diverse Late Pleistocene Siberian
      population and the small Holocene Wrangel population. Our results indicate that
      mitogenome diversity was reduced to one single haplotype at the time of the
      isolation, and thus that the Holocene Wrangel Island population was established
      by a single maternal lineage. Moreover, we show that the ensuing small effective
      population size coincided with fixation of a nonsynonymous mutation, and a
      comparative analysis of mutation rates suggests that the evolutionary rate was
      accelerated in the Holocene population. These results suggest that isolation on
      Wrangel Island led to an increase in the frequency of deleterious genetic
      variation, and thus are consistent with the hypothesis that strong genetic drift
      in small populations leads to purifying selection being less effective in
      removing deleterious mutations.

PMID- 30283658
TI  - Evolution and comparative ecology of parthenogenesis in haplodiploid arthropods.
AB  - Changes from sexual reproduction to female-producing parthenogenesis (thelytoky)
      have great evolutionary and ecological consequences, but how many times
      parthenogenesis evolved in different animal taxa is unknown. We present the first
      exhaustive database covering 765 cases of parthenogenesis in haplodiploid
      (arrhenotokous) arthropods, and estimate frequencies of parthenogenesis in
      different taxonomic groups. We show that the frequency of parthenogenetic
      lineages extensively varies among groups (0-38% among genera), that many species
      have both sexual and parthenogenetic lineages and that polyploidy is very rare.
      Parthenogens are characterized by broad ecological niches: parasitoid and
      phytophagous parthenogenetic species consistently use more host species, and have
      larger, polewards extended geographic distributions than their sexual relatives.
      These differences did not solely evolve after the transition to parthenogenesis.
      Extant parthenogens often derive from sexual ancestors with relatively broad
      ecological niches and distributions. As these ecological attributes are
      associated with large population sizes, our results strongly suggests that
      transitions to parthenogenesis are more frequent in large sexual populations
      and/or that the risk of extinction of parthenogens with large population sizes is
      reduced. The species database presented here provides insights into the
      maintenance of sex and parthenogenesis in natural populations that are not taxon
      specific and opens perspectives for future comparative studies.

PMID- 30283660
TI  - How should we interpret estimates of individual repeatability?
AB  - Individual repeatability (R), defined as the proportion of observed variance
      attributable to among-individual differences, is a widely used summary statistic
      in evolutionarily motivated studies of morphology, life history, physiology and,
      especially, behaviour. Although statistical methods to estimate R are well known
      and widely available, there is a growing tendency for researchers to interpret R
      in ways that are subtly, but importantly, different. Some view R as a property of
      a dataset and a statistic to be interpreted agnostically with respect to
      mechanism. Others wish to isolate the contributions of 'intrinsic' and/or
      'permanent' individual differences, and draw a distinction between true
      (intrinsic) and pseudo-repeatability arising from uncontrolled extrinsic effects.
      This latter view proposes a narrower, more mechanistic interpretation, than the
      traditional concept of repeatability, but perhaps one that allows stronger
      evolutionary inference as a consequence (provided analytical pitfalls are
      successfully avoided). Neither perspective is incorrect, but if we are to avoid
      confusion and fruitless debate, there is a need for researchers to recognise this
      dichotomy, and to ensure clarity in relation to how, and why, a particular
      estimate of R is appropriate in any case.

PMID- 30283659
TI  - Egg chemoattractants moderate intraspecific sperm competition.
AB  - Interactions among eggs and sperm are often assumed to generate intraspecific
      variation in reproductive fitness, but the specific gamete-level mechanisms
      underlying competitive fertilization success remain elusive in most species.
      Sperm chemotaxis-the attraction of sperm by egg-derived chemicals-is a ubiquitous
      form of gamete signaling, occurring throughout the animal and plant kingdoms. The
      chemical cues released by eggs are known to act at the interspecific level (e.g.,
      facilitating species recognition), but recent studies have suggested that they
      could have roles at the intraspecific level by moderating sperm competition.
      Here, we exploit the experimental tractability of a broadcast spawning marine
      invertebrate to test this putative mechanism of gamete-level sexual selection. We
      use a fluorescently labeled mitochondrial dye in mussels to track the real-time
      success of sperm as they compete to fertilize eggs, and provide the first direct
      evidence in any species that competitive fertilization success is moderated by
      differential sperm chemotaxis. Furthermore, our data are consistent with the idea
      that egg chemoattractants selectively attract ejaculates from genetically
      compatible males, based on relationships inferred from both nuclear and
      mitochondrial genetic markers. These findings for a species that exhibits the
      ancestral reproductive strategy of broadcast spawning have important implications
      for the numerous species that also rely on egg chemoattractants to attract sperm,
      including humans, and have potentially important implications for our
      understanding of the evolutionary cascade of sexual selection.

PMID- 30283661
TI  - Ancient genomic variation underlies repeated ecological adaptation in young
      stickleback populations.
AB  - Adaptation in the wild often involves standing genetic variation (SGV), which
      allows rapid responses to selection on ecological timescales. However, we still
      know little about how the evolutionary histories and genomic distributions of SGV
      influence local adaptation in natural populations. Here, we address this
      knowledge gap using the threespine stickleback fish (Gasterosteus aculeatus) as a
      model. We extend restriction site-associated DNA sequencing (RAD-seq) to produce
      phased haplotypes approaching 700 base pairs (bp) in length at each of over
      50,000 loci across the stickleback genome. Parallel adaptation in two
      geographically isolated freshwater pond populations consistently involved
      fixation of haplotypes that are identical-by-descent. In these same genomic
      regions, sequence divergence between marine and freshwater stickleback, as
      measured by dXY , reaches tenfold higher than background levels and genomic
      variation is structured into distinct marine and freshwater haplogroups. By
      combining this dataset with a de novo genome assembly of a related species, the
      ninespine stickleback (Pungitius pungitius), we find that this habitat-associated
      divergent variation averages six million years old, nearly twice the genome-wide
      average. The genomic variation that is involved in recent and rapid local
      adaptation in stickleback has therefore been evolving throughout the 15-million
      year history since the two species lineages split. This long history of genomic
      divergence has maintained large genomic regions of ancient ancestry that include
      multiple chromosomal inversions and extensive linked variation. These discoveries
      of ancient genetic variation spread broadly across the genome in stickleback
      demonstrate how selection on ecological timescales is a result of genome
      evolution over geological timescales, and vice versa.

PMID- 30283663
TI  - Sexual competition and the evolution of condition-dependent ageing.
AB  - Increased individual resources (condition) can be correlated with either
      increased or decreased longevity. While variation in resource acquisition and
      allocation can account for some of this variation, the general conditions that
      select for either pattern remain unclear. Previous models suggest that
      nonlinearity of payoffs from investment in reproduction (e.g., male secondary
      sexual traits) can select for high-condition individuals that sacrifice longevity
      to increase reproductive opportunity. However, it remains unclear what mating
      systems or patterns of sexual competition might select for such life-history
      strategies. We used a model of condition-dependent investment to explore how
      expected payoffs from increased expression of secondary sexual traits affect
      optimal investment in lifespan. We find that nonlinearity of these payoffs
      results in a negative relationship between condition and lifespan under two
      general conditions: first, when there are accelerating marginal benefits from
      increasing investment; second, when individuals that invest minimally in
      secondary sexual trait expression can still achieve matings. In the second
      scenario, the negative relationship occurs due to selection on low-condition
      individuals to extend lifespan at the cost of secondary sexual trait expression.
      Our findings clarify the potential role of sexual selection in shaping patterns
      of condition-dependent ageing, and highlight the importance of considering the
      strategies of both low- and high-condition individuals when investigating
      patterns of condition-dependent ageing.

PMID- 30283662
TI  - Genomic associations with bill length and disease reveal drift and selection
      across island bird populations.
AB  - Island species provide excellent models for investigating how selection and drift
      operate in wild populations, and for determining how these processes act to
      influence local adaptation and speciation. Here, we examine the role of selection
      and drift in shaping genomic and phenotypic variation across recently separated
      populations of Berthelot's pipit (Anthus berthelotii), a passerine bird endemic
      to three archipelagos in the Atlantic. We first characterized genetic diversity
      and population structuring that supported previous inferences of a history of
      recent colonizations and bottlenecks. We then tested for regions of the genome
      associated with the ecologically important traits of bill length and malaria
      infection, both of which vary substantially across populations in this species.
      We identified a SNP associated with variation in bill length among individuals,
      islands, and archipelagos; patterns of variation at this SNP suggest that both
      phenotypic and genotypic variation in bill length is largely shaped by founder
      effects. Malaria was associated with SNPs near/within genes involved in the
      immune response, but this relationship was not consistent among archipelagos,
      supporting the view that disease resistance is complex and rapidly evolving.
      Although we found little evidence for divergent selection at candidate loci for
      bill length and malaria resistance, genome scan analyses pointed to several genes
      related to immunity and metabolism as having important roles in divergence and
      adaptation. Our findings highlight the utility and challenges involved with
      combining association mapping and population genetic analysis in nonequilibrium
      populations, to disentangle the effects of drift and selection on shaping
      genotypes and phenotypes.

PMID- 30283664
TI  - Male-biased gene expression resolves sexual conflict through the evolution of sex
      specific genetic architecture.
AB  - Many genes are subject to contradictory selection pressures in males and females,
      and balancing selection resulting from sexual conflict has the potential to
      substantially increase standing genetic diversity in populations and thereby act
      as an important force in adaptation. However, the underlying causes of sexual
      conflict, and the potential for resolution, remains hotly debated. Using
      transcriptome-resequencing data from male and female guppies, we use a novel
      approach, combining patterns of genetic diversity and intersexual divergence in
      allele frequency, to distinguish the different scenarios that give rise to sexual
      conflict, and how this conflict may be resolved through regulatory evolution. We
      show that reproductive fitness is the main source of sexual conflict, and this is
      resolved via the evolution of male-biased expression. Furthermore, resolution of
      sexual conflict produces significant differences in genetic architecture between
      males and females, which in turn lead to specific alleles influencing sex
      specific viability. Together, our findings suggest an important role for sexual
      conflict in shaping broad patterns of genome diversity, and show that regulatory
      evolution is a rapid and efficient route to the resolution of conflict.

PMID- 30283665
TI  - Parallel evolution of gene expression between trophic specialists despite
      divergent genotypes and morphologies.
AB  - Parallel evolution of gene expression commonly underlies convergent niche
      specialization, but parallel changes in expression could also underlie divergent
      specialization. We investigated divergence in gene expression and whole-genome
      genetic variation across three sympatric Cyprinodon pupfishes endemic to San
      Salvador Island, Bahamas. This recent radiation consists of a generalist and two
      derived specialists adapted to novel niches: a scale-eating and a snail-eating
      pupfish. We sampled total mRNA from all three species at two early developmental
      stages and compared gene expression with whole-genome genetic differentiation
      among all three species in 42 resequenced genomes. Eighty percent of genes that
      were differentially expressed between snail-eaters and generalists were up or
      down regulated in the same direction between scale-eaters and generalists;
      however, there were no fixed variants shared between species underlying these
      parallel changes in expression. Genes showing parallel evolution of expression
      were enriched for effects on metabolic processes, whereas genes showing divergent
      expression were enriched for effects on cranial skeleton development and pigment
      biosynthesis, reflecting the most divergent phenotypes observed between
      specialist species. Our findings reveal that even divergent niche specialists may
      exhibit convergent adaptation to higher trophic levels through shared genetic
      pathways. This counterintuitive result suggests that parallel evolution in gene
      expression can accompany divergent ecological speciation during adaptive
      radiation.

PMID- 30283666
TI  - Comparative analysis examining patterns of genomic differentiation across
      multiple episodes of population divergence in birds.
AB  - Heterogeneous patterns of genomic differentiation are commonly documented between
      closely related populations and there is considerable interest in identifying
      factors that contribute to their formation. These factors could include genomic
      features (e.g., areas of low recombination) that promote processes like linked
      selection (positive or purifying selection that affects linked neutral sites) at
      specific genomic regions. Examinations of repeatable patterns of differentiation
      across population pairs can provide insight into the role of these factors. Birds
      are well suited for this work, as genome structure is conserved across this
      group. Accordingly, we reestimated relative (FST ) and absolute (dXY )
      differentiation between eight sister pairs of birds that span a broad taxonomic
      range using a common pipeline. Across pairs, there were modest but significant
      correlations in window-based estimates of differentiation (up to 3% of variation
      explained for FST and 26% for dXY ), supporting a role for processes at conserved
      genomic features in generating heterogeneous patterns of differentiation;
      processes specific to each episode of population divergence likely explain the
      remaining variation. The role genomic features play was reinforced by linear
      models identifying several genomic variables (e.g., gene densities) as
      significant predictors of FST and dXY repeatability. FST repeatability was higher
      among pairs that were further along the speciation continuum (i.e., more
      reproductively isolated) providing further insight into how genomic
      differentiation changes with population divergence; early stages of speciation
      may be dominated by positive selection that is different between pairs but
      becomes integrated with processes acting according to shared genomic features as
      speciation proceeds.

PMID- 30283667
TI  - Horizontal gene cluster transfer increased hallucinogenic mushroom diversity.
AB  - Secondary metabolites are a heterogeneous class of chemicals that often mediate
      interactions between species. The tryptophan-derived secondary metabolite,
      psilocin, is a serotonin receptor agonist that induces altered states of
      consciousness. A phylogenetically disjunct group of mushroom-forming fungi in the
      Agaricales produce the psilocin prodrug, psilocybin. Spotty phylogenetic
      distributions of fungal compounds are sometimes explained by horizontal transfer
      of metabolic gene clusters among unrelated fungi with overlapping niches. We
      report the discovery of a psilocybin gene cluster in three hallucinogenic
      mushroom genomes, and evidence for its horizontal transfer between fungal
      lineages. Patterns of gene distribution and transmission suggest that synthesis
      of psilocybin may have provided a fitness advantage in the dung and late wood
      decay fungal niches, which may serve as reservoirs of fungal indole-based
      metabolites that alter behavior of mycophagous and wood-eating invertebrates.
      These hallucinogenic mushroom genomes will serve as models in neurochemical
      ecology, advancing the (bio)prospecting and synthetic biology of novel
      neuropharmaceuticals.

PMID- 30283669
TI  - Superior stimulation of female fecundity by subordinate males provides a
      mechanism for telegony.
AB  - When females mate promiscuously, rival males compete to fertilise the ova. In
      theory, a male can increase his success at siring offspring by inducing the
      female to lay more eggs, as well as by producing more competitive sperm. Here we
      report that the evolutionary consequences of fecundity stimulation extend beyond
      rival males, by experimentally uncovering effects on offspring. With experiments
      on the burying beetle Nicrophorus vespilloides, we show that smaller subordinate
      males are better able to stimulate female fecundity than larger, dominant males.
      Furthermore dominant males also benefit from the greater fecundity induced by
      smaller males, and so gain from the female's earlier promiscuity - just as
      predicted by theory. By inducing females to produce more offspring on a limited
      resource, smaller males cause each larva to be smaller, even those they do not
      sire themselves. Fecundity stimulation thus promotes the non-genetic inheritance
      of offspring body size, and provides a mechanism for telegony.

PMID- 30283668
TI  - Energy demand and the context-dependent effects of genetic interactions
      underlying metabolism.
AB  - Genetic effects are often context dependent, with the same genotype
      differentially affecting phenotypes across environments, life stages, and sexes.
      We used an environmental manipulation designed to increase energy demand during
      development to investigate energy demand as a general physiological explanation
      for context-dependent effects of mutations, particularly for those mutations that
      affect metabolism. We found that increasing the photoperiod during which
      Drosophila larvae are active during development phenocopies a temperature
      dependent developmental delay in a mitochondrial-nuclear genotype with disrupted
      metabolism. This result indicates that the context-dependent fitness effects of
      this genotype are not specific to the effects of temperature and may generally
      result from variation in energy demand. The effects of this genotype also differ
      across life stages and between the sexes. The mitochondrial-nuclear genetic
      interaction disrupts metabolic rate in growing larvae, but not in adults, and
      compromises female, but not male, reproductive fitness. These patterns are
      consistent with a model where context-dependent genotype-phenotype relationships
      may generally arise from differences in energy demand experienced by individuals
      across environments, life stages, and sexes.

PMID- 30283670
TI  - Life-history correlations change under coinfection leading to higher pathogen
      load.
AB  - The ability of a parasite strain to establish and grow on its host may be
      drastically altered by simultaneous infection by other parasite strains. However,
      we still lack an understanding of how life-history allocations may change under
      coinfection, although life-history correlations are a critical mechanism
      restricting the evolutionary potential and epidemiological dynamics of pathogens.
      Here, we study how life-history stages and their correlations change in the
      obligate fungal pathogen Podosphaera plantaginis under single infection and
      coinfection scenarios. We find increased pathogen loads under coinfection, but
      this is not explained by an enhanced performance at any of the life-history
      stages that constitute infections. Instead, we show that under coinfection the
      correlation between timing of sporulation and final pathogen load becomes
      positive. The changes in pathogen life-history allocations leading to more severe
      infections under coinfection can have far-reaching epidemiological consequences,
      as well as implication for our understanding of the evolution of virulence.

PMID- 30283671
TI  - The emergence, maintenance, and demise of diversity in a spatially variable
      antibiotic regime.
AB  - Antimicrobial resistance (AMR) is a growing global threat that, in the absence of
      new antibiotics, requires effective management of existing drugs. Here, we use
      experimental evolution of the opportunistic human pathogen Pseudomonas aeruginosa
      to explore how changing patterns of drug delivery modulates the spread of
      resistance in a population. Resistance evolves readily under both temporal and
      spatial variation in drug delivery and fixes rapidly under temporal, but not
      spatial, variation. Resistant and sensitive genotypes coexist in spatially
      varying conditions due to a resistance-growth rate trade-off which, when coupled
      to dispersal, generates negative frequency-dependent selection and a quasi
      protected polymorphism. Coexistence is ultimately lost, however, because
      resistant types with improved growth rates in the absence of drug spread through
      the population. These results suggest that spatially variable drug prescriptions
      can delay but not prevent the spread of resistance and provide a striking example
      of how the emergence and eventual demise of biodiversity is underpinned by
      evolving fitness trade-offs.

PMID- 30283672
TI  - Gender equity at scientific events.
AB  - Although the proportion of women in science, and in evolutionary biology in
      particular, has substantially increased over the last century, women remain
      underrepresented in academia, especially at senior levels. In addition, their
      scientific achievements do not always receive the same level of recognition as do
      men's, which can be reflected in a lower relative representation of women among
      invited speakers at conferences or specialized courses. Using announcements sent
      to the EvolDir mailing list between April 2016 and September 2017, and the
      symposium programs of three large evolutionary biology congresses held in summer
      2017, we quantified the representation of women announced as invited speakers in
      conferences, congress symposia, and specialized courses. We compared the
      proportion of invited women to a baseline estimated using membership data of the
      associated scientific societies, and surveyed organizers to investigate their
      influence and that of potential gender-ratio guidelines on the proportion of
      invited women. We find that the average proportion of invited women is comparable
      (conferences), significantly lower (specialized courses), or significantly higher
      (congress symposia) than the current baseline (32% women). It is positively
      correlated to the proportion of women among the organizers, and it is on average
      higher for events whose organizers considered gender when choosing speakers than
      for those whose organizers did not. To investigate the impact of Equal
      Opportunity guidelines, we then collected longitudinal data on the proportion of
      invited women at two series of congresses, covering the 2001-2017 period. The
      proportion of invited women is higher when Equal Opportunity guidelines are
      announced. Encouraging women to sit on organizing committees of scientific
      events, and the establishment of visible Equal Opportunity guidelines, thus could
      be ways to ensure higher number of invited female speakers in the future. Our
      results suggest that change, if desired, requires deliberate actions.

PMID- 30283673
TI  - Is there indirect selection on female extra-pair reproduction through cross-sex
      genetic correlations with male reproductive fitness?
AB  - One key hypothesis explaining the evolution and persistence of polyandry, and
      resulting female extra-pair reproduction in socially monogamous systems, is that
      female propensity for extra-pair reproduction is positively genetically
      correlated with male reproductive fitness and consequently experiences positive
      cross-sex indirect selection. However, key genetic correlations have rarely been
      estimated, especially in free-living populations experiencing natural
      (co)variation in reproductive strategies and fitness. We used long-term life
      history and pedigree data from song sparrows (Melospiza melodia) to estimate the
      cross-sex genetic correlation between female propensity for extra-pair
      reproduction and adult male lifetime reproductive success, and thereby test a key
      hypothesis regarding mating system evolution. There was substantial additive
      genetic variance in both traits, providing substantial potential for indirect
      selection on female reproductive strategy. However, the cross-sex genetic
      correlation was estimated to be close to zero. Such small correlations might
      arise because male reproductive success achieved through extra-pair paternity was
      strongly positively genetically correlated with success achieved through within
      pair paternity, implying that the same successful males commonly sire offspring
      produced by polyandrous and monogamous females. Cross-sex indirect selection may
      consequently have limited capacity to drive evolution of female extra-pair
      reproduction, or hence underlying polyandry, in systems where multiple routes to
      paternity success exist.

PMID- 30283675
TI  - Last male sperm precedence is modulated by female remating rate in Drosophila
      melanogaster.
AB  - Following multiple matings, sperm from different males compete for fertilization
      within the female reproductive tract. In many species, this competition results
      in an unequal sharing of paternity that favors the most recent mate, termed last
      male sperm precedence (LMSP). Much of our understanding of LMSP comes from
      studies in Drosophila melanogaster that focus on twice-mated females with
      standardized latencies between successive matings. Despite accumulating evidence
      indicating that females often mate with more than two males and exhibit variation
      in the latency between matings, the consequences of mating rate on LMSP are
      poorly understood. Here, we developed a paradigm utilizing D. melanogaster in
      which females remated at various time intervals with either two or three
      transgenic males that produce fluorescent sperm (green, red, or blue). This
      genetic manipulation enables paternity assessment of offspring and male-specific
      sperm fate examination in female reproductive tracts. We found that remating
      latency had no relationship with LMSP in females that mated with two males.
      However, LMSP was significantly reduced in thrice-mated females with short
      remating intervals; coinciding with reduced last-male sperm storage. Thus, female
      remating rate influences the relative share of paternity, the overall clutch
      paternity diversity, and ultimately the acquisition of indirect genetic benefits
      to potentially maximize female reproductive success.

PMID- 30283676
TI  - A general model of biological signals, from cues to handicaps.
AB  - Organisms sometimes appear to use extravagant traits, or "handicaps", to signal
      their quality to an interested receiver. Before they were used as signals, many
      of these traits might have been selected to increase with individual quality for
      reasons apart from conveying information, allowing receivers to use the traits as
      "cues" of quality. However, current theory does not explain when and why cues of
      individual quality become exaggerated into costly handicaps. We address this
      here, using a game-theoretic model of adaptive signalling. Our model predicts
      that: (1) signals will honestly reflect signaler quality whenever there is a
      positive relationship between individual quality and the signalling trait's
      naturally selected, non-informational optimum; and (2) the slope of this
      relationship will determine the amount of costly signal exaggeration, with more
      exaggeration favored when the slope is more shallow. A shallow slope means that a
      lower quality male would pay only a small fitness cost to have the same trait
      value as a higher quality male, and this drives the exaggeration of signals as
      high-quality signalers are selected to distinguish themselves. Our model reveals
      a simple and potentially widespread mechanism for ensuring signal honesty and
      predicts a natural continuum of signalling strategies, from cost-free cues to
      costly handicaps.

PMID- 30283674
TI  - Strong hybrid male incompatibilities impede the spread of a selfish chromosome
      between populations of a fly.
AB  - Meiotically driving sex chromosomes manipulate gametogenesis to increase their
      transmission at a cost to the rest of the genome. The intragenomic conflicts they
      produce have major impacts on the ecology and evolution of their host species.
      However, their ecological dynamics remain poorly understood. Simple population
      genetic models predict meiotic drivers will rapidly reach fixation in populations
      and spread across landscapes. In contrast, natural populations commonly show
      spatial variation in the frequency of drivers, with drive present in clines or
      mosaics across species ranges. For example, Drosophila subobscura harbors a sex
      ratio distorting drive chromosome (SRs) at 15-25% frequency in North Africa,
      present at less than 2% frequency in adjacent southern Spain, and absent in other
      European populations. Here, we investigate the forces preventing the spread of
      the driver northward. We show that SRs has remained at a constant frequency in
      North Africa, and failed to spread in Spain. We find strong evidence that spread
      is impeded by genetic incompatibility between SRs and Spanish autosomal
      backgrounds. When we cross SRs from North Africa onto Spanish genetic backgrounds
      we observe strong incompatibilities specific to hybrids bearing SRs. The
      incompatibilities increase in severity in F2 male hybrids, leading to almost
      complete infertility. We find no evidence supporting an alternative hypothesis,
      that there is resistance to drive in Spanish populations. We conclude that the
      source of the stepped frequency variation is genetic incompatibility between the
      SRs chromosome and the genetic backgrounds of the adjacent population, preventing
      SRs spreading northward. The low frequency of SRs in South Spain is consistent
      with recurrent gene flow across the Strait of Gibraltar combined with selection
      against the SRs element through genetic incompatibility. This demonstrates that
      incompatibilities between drive chromosomes and naive populations can prevent the
      spread of drive between populations, at a continental scale.

PMID- 30283677
TI  - Recent admixture between species of the fungal pathogen Histoplasma.
AB  - Hybridization between species of pathogens has the potential to speed evolution
      of virulence by providing the raw material for adaptation through introgression
      or by assembling new combinations of virulence traits. Fungal diseases are a
      source high morbidity, and remain difficult to treat. Yet the frequency of
      hybridization between fungal species has rarely been explored, and the functional
      role of introgressed alleles remains largely unknown. Histoplasma mississippiense
      and H. ohiense are sympatric throughout their range in North America and have
      distinct virulence strategies, making them an ideal system to examine the role
      introgression may play in fungal pathogens. We identified introgressed tracts in
      the genomes of a sample of H. mississippiense and H. ohiense isolates. We found
      strong evidence in each species for recent admixture, but introgressed alleles
      were present at low frequencies, suggesting that they were deleterious.
      Consistent with this, coding and regulatory sequences were strongly depleted
      within introgressed regions, whereas intergenic regions were enriched, indicating
      that functional introgressed alleles were frequently deleterious in their new
      genomic context. Surprisingly, we found only two isolates with substantial
      admixture: the H. mississippiense and H. ohiense genomic reference strains, WU24
      and G217B, respectively. Our results show that recent admixture has occurred,
      that it is frequently deleterious and that conclusions based on studies of the H.
      mississippiense and H. ohiense type strains should be revisited with more
      representative samples from the genus.

PMID- 30283678
TI  - Evolution of bacteria specialization along an antibiotic dose gradient.
AB  - Antibiotic and pesticide resistance of pathogens are major and pressing worldwide
      issues. Resistance evolution is often considered in simplified ecological
      contexts: treated versus nontreated environments. In contrast, antibiotic usually
      present important dose gradients: from ecosystems to hospitals to polluted soils,
      in treated patients across tissues. However, we do not know whether adaptation to
      low or high doses involves different phenotypic traits, and whether these traits
      trade-off with each other. In this study, we investigated the occurrence of such
      fitness trade-offs along a dose gradient by evolving experimentally resistant
      lines of Escherichia coli at different antibiotic concentrations for ~400
      generations. Our results reveal fast evolution toward specialization following
      the first mutational step toward resistance, along with pervasive trade-offs
      among different evolution doses. We found clear and regular fitness patterns of
      specialization, which converged rapidly from different initial starting points.
      These findings are consistent with a simple fitness peak shift model as described
      by the classical evolutionary ecology theory of adaptation across environmental
      gradients. We also found that the fitness costs of resistance tend to be
      compensated through time at low doses whereas they increase through time at
      higher doses. This cost evolution follows a linear trend with the log-dose of
      antibiotic along the gradient. These results suggest a general explanation for
      the variability of the fitness costs of resistance and their evolution. Overall,
      these findings call for more realistic models of resistance management
      incorporating dose-specialization.

PMID- 30283679
TI  - Genetic conflict with a parasitic nematode disrupts the legume-rhizobia
      mutualism.
AB  - Genetic variation for partner quality in mutualisms is an evolutionary paradox.
      One possible resolution to this puzzle is that there is a tradeoff between
      partner quality and other fitness-related traits. Here, we tested whether
      susceptibility to parasitism is one such tradeoff in the mutualism between
      legumes and nitrogen-fixing bacteria (rhizobia). We performed two greenhouse
      experiments with the legume Medicago truncatula. In the first, we inoculated each
      plant with the rhizobia Ensifer meliloti and with one of 40 genotypes of the
      parasitic root-knot nematode Meloidogyne hapla. In the second experiment, we
      inoculated all plants with rhizobia and half of the plants with a genetically
      variable population of nematodes. Using the number of nematode galls as a proxy
      for infection severity, we found that plant genotypes differed in susceptibility
      to nematode infection, and nematode genotypes differed in infectivity. Second, we
      showed that there was a genetic correlation between the number of mutualistic
      structures formed by rhizobia (nodules) and the number of parasitic structures
      formed by nematodes (galls). Finally, we found that nematodes disrupt the
      rhizobia mutualism: nematode-infected plants formed fewer nodules and had less
      nodule biomass than uninfected plants. Our results demonstrate that there is
      genetic conflict between attracting rhizobia and repelling nematodes in Medicago.
      If genetic conflict with parasitism is a general feature of mutualism, it could
      account for the maintenance of genetic variation in partner quality and influence
      the evolutionary dynamics of positive species interactions.

PMID- 30283680
TI  - Mutual fitness benefits arise during coevolution in a nematode-defensive microbe
      model.
AB  - Species interactions can shift along the parasitism-mutualism continuum. However,
      the consequences of these transitions for coevolutionary interactions remain
      unclear. We experimentally coevolved a novel species interaction between
      Caenorhabditis elegans hosts and a mildly parasitic bacterium, Enterococcus
      faecalis, with host-protective properties against virulent Staphylococcus aureus.
      Coinfections drove the evolutionary transition of the C. elegans-E. faecalis
      relationship toward a reciprocally beneficial interaction. As E. faecalis evolved
      to protect nematodes against S. aureus infection, hosts adapted by accommodating
      greater numbers of protective bacteria. The mutualism was strongest in pairings
      of contemporary coevolved populations. To generally assess the conditions under
      which these defensive mutualisms can arise and coevolve, we analyzed a model that
      showed that they are favored when mild parasites confer an intermediate level of
      protection. Our results reveal that coevolution can shape the transition of
      animal-parasite interactions toward defensive symbioses in response to
      coinfections.

PMID- 30283681
TI  - A note on measuring natural selection on principal component scores.
AB  - Measuring natural selection through the use of multiple regression has
      transformed our understanding of selection, although the methods used remain
      sensitive to the effects of multicollinearity due to highly correlated traits.
      While measuring selection on principal component (PC) scores is an apparent
      solution to this challenge, this approach has been heavily criticized due to
      difficulties in interpretation and relating PC axes back to the original traits.
      We describe and illustrate how to transform selection gradients for PC scores
      back into selection gradients for the original traits, addressing issues of
      multicollinearity and biological interpretation. In addition to reducing
      multicollinearity, we suggest that this method may have promise for measuring
      selection on high-dimensional data such as volatiles or gene expression traits.
      We demonstrate this approach with empirical data and examples from the
      literature, highlighting how selection estimates for PC scores can be interpreted
      while reducing the consequences of multicollinearity.

PMID- 30283682
TI  - Speciation genes are more likely to have discordant gene trees.
AB  - Speciation genes are responsible for reproductive isolation between species. By
      directly participating in the process of speciation, the genealogies of isolating
      loci have been thought to more faithfully represent species trees. The unique
      properties of speciation genes may provide valuable evolutionary insights and
      help determine the true history of species divergence. Here, we formally analyze
      whether genealogies from loci participating in Dobzhansky-Muller (DM)
      incompatibilities are more likely to be concordant with the species tree under
      incomplete lineage sorting (ILS). Individual loci differ stochastically from the
      true history of divergence with a predictable frequency due to ILS, and these
      expectations-combined with the DM model of intrinsic reproductive isolation from
      epistatic interactions-can be used to examine the probability of concordance at
      isolating loci. Contrary to existing verbal models, we find that reproductively
      isolating loci that follow the DM model are often more likely to have discordant
      gene trees. These results are dependent on the pattern of isolation observed
      between three species, the time between speciation events, and the time since the
      last speciation event. Results supporting a higher probability of discordance are
      found for both derived-derived and derived-ancestral DM pairs, and regardless of
      whether incompatibilities are allowed or prohibited from segregating in the same
      population. Our overall results suggest that DM loci are unlikely to be
      especially useful for reconstructing species relationships, even in the presence
      of gene flow between incipient species, and may in fact be positively misleading.

PMID- 30283683
TI  - Clines on the seashore: The genomic architecture underlying rapid divergence in
      the face of gene flow.
AB  - Adaptive divergence and speciation may happen despite opposition by gene flow.
      Identifying the genomic basis underlying divergence with gene flow is a major
      task in evolutionary genomics. Most approaches (e.g., outlier scans) focus on
      genomic regions of high differentiation. However, not all genomic architectures
      potentially underlying divergence are expected to show extreme differentiation.
      Here, we develop an approach that combines hybrid zone analysis (i.e., focuses on
      spatial patterns of allele frequency change) with system-specific simulations to
      identify loci inconsistent with neutral evolution. We apply this to a genome-wide
      SNP set from an ideally suited study organism, the intertidal snail Littorina
      saxatilis, which shows primary divergence between ecotypes associated with
      different shore habitats. We detect many SNPs with clinal patterns, most of which
      are consistent with neutrality. Among non-neutral SNPs, most are located within
      three large putative inversions differentiating ecotypes. Many non-neutral SNPs
      show relatively low levels of differentiation. We discuss potential reasons for
      this pattern, including loose linkage to selected variants, polygenic adaptation
      and a component of balancing selection within populations (which may be expected
      for inversions). Our work is in line with theory predicting a role for inversions
      in divergence, and emphasizes that genomic regions contributing to divergence may
      not always be accessible with methods purely based on allele frequency
      differences. These conclusions call for approaches that take spatial patterns of
      allele frequency change into account in other systems.

PMID- 30283684
TI  - Adaptive radiation along a deeply conserved genetic line of least resistance in
      Anolis lizards.
AB  - On microevolutionary timescales, adaptive evolution depends upon both natural
      selection and the underlying genetic architecture of traits under selection,
      which may constrain evolutionary outcomes. Whether such genetic constraints shape
      phenotypic diversity over macroevolutionary timescales is more controversial,
      however. One key prediction is that genetic constraints should bias the early
      stages of species divergence along "genetic lines of least resistance" defined by
      the genetic (co)variance matrix, G. This bias is expected to erode over time as
      species means and G matrices diverge, allowing phenotypes to evolve away from the
      major axis of variation. We tested for evidence of this signal in West Indian
      Anolis lizards, an iconic example of adaptive radiation. We found that the major
      axis of morphological evolution was well aligned with a major axis of genetic
      variance shared by all species despite separation times of 20-40 million years,
      suggesting that divergence occurred along a conserved genetic line of least
      resistance. Further, this signal persisted even as G itself evolved, apparently
      because the largest evolutionary changes in G were themselves aligned with the
      line of genetic least resistance. Our results demonstrate that the signature of
      genetic constraint may persist over much longer timescales than previously
      appreciated, even in the presence of evolving genetic architecture. This pattern
      may have arisen either because pervasive constraints have biased the course of
      adaptive evolution or because the G matrix itself has been shaped by selection to
      conform to the adaptive landscape.

PMID- 30283685
TI  - Lessons from a natural experiment: Allopatric morphological divergence and
      sympatric diversification in the Midas cichlid species complex are largely
      influenced by ecology in a deterministic way.
AB  - Explaining why some lineages diversify while others do not and how are key
      objectives in evolutionary biology. Young radiations of closely related species
      derived from the same source population provide an excellent opportunity to
      disentangle the relative contributions of possible drivers of diversification. In
      these settings, lineage-specific effects are shared and can be ruled out.
      Moreover, the relevant demographic and ecological parameters can be estimated
      accurately. Midas cichlid fish in Nicaragua have repeatedly colonized several
      crater lakes, diverged from the same source populations, and, interestingly,
      diversified in some of them but not others. Here, using the most comprehensive
      molecular and geometric morphometric data set on Midas cichlids to date (~20,000
      SNPs, 12 landmarks, ~700 individuals), we aim to understand why and how crater
      lake populations diverge and why some of them are more prone to diversify in
      sympatry than others. Taking ancestor-descendant relationships into account, we
      find that Midas cichlids diverged in parallel from their source population mostly
      but not exclusively-by evolving more slender body shapes in all six investigated
      crater lakes. Admixture among crater lakes has possibly facilitated this process
      in one case, but overall, admixture and secondary waves of colonization cannot
      predict morphological divergence and intralacustrine diversification. Instead,
      morphological divergence is larger the more dissimilar a crater lake is compared
      to the source lake and happens rapidly after colonization followed by a slow-down
      with time. Our data also provide some evidence that founder effects may
      positively contribute to divergence. The depth of a crater lake is positively
      associated with variation in body shapes (and number of species), presumably by
      providing more ecological opportunities. In conclusion, we find that parallel
      morphological divergence in allopatry and the propensity for diversification in
      sympatry across the entire Midas cichlid fish radiation is partly predictable and
      mostly driven by ecology.

PMID- 30283686
TI  - Convergent phenotypic evolution of the visual system via different molecular
      routes: How Neotropical cichlid fishes adapt to novel light environments.
AB  - How predictable is evolution? This remains a fundamental but contested issue in
      evolutionary biology. When independent lineages colonize the same environment, we
      are presented with a natural experiment that allows us to ask if genetic and
      ecological differences promote species-specific evolutionary outcomes or whether
      species phenotypically evolve in a convergent manner in response to shared
      selection pressures. If so, are the molecular mechanisms underlying phenotypic
      convergence the same? In Nicaragua, seven species of cichlid fishes concurrently
      colonized two novel photic environments. Hence, their visual system represents a
      compelling model to address these questions, particularly since the adaptive
      value of phenotypic changes is well-understood. By analyzing retinal
      transcriptomes, we found that differential expression of genes responsible for
      color vision (cone opsins and cyp27c1) produced rapid and mostly convergent
      changes of predicted visual sensitivities. Notably, these changes occurred in the
      same direction in all species although there were differences in underlying gene
      expression patterns illustrating nonconvergence at the molecular level. Adaptive
      phenotypes evolved deterministically, even when species differ substantially in
      ecology and genetic variation. This provides strong evidence that phenotypic
      evolution of the visual system occurred in response to similar selective forces
      of the photic environment.

PMID- 30283687
TI  - Parallel genetic adaptation across environments differing in mode of growth or
      resource availability.
AB  - Evolution experiments have demonstrated high levels of genetic parallelism
      between populations evolving in identical environments. However, natural
      populations evolve in complex environments that can vary in many ways, likely
      sharing some characteristics but not others. Here, we ask whether shared
      selection pressures drive parallel evolution across distinct environments. We
      addressed this question in experimentally evolved populations founded from a
      clone of the bacterium Burkholderia cenocepacia. These populations evolved for 90
      days (approximately 600 generations) under all combinations of high or low carbon
      availability and selection for either planktonic or biofilm modes of growth.
      Populations that evolved in environments with shared selection pressures (either
      level of carbon availability or mode of growth) were more genetically similar to
      each other than populations from environments that shared neither characteristic.
      However, not all shared selection pressures led to parallel evolution. Genetic
      parallelism between low-carbon biofilm and low-carbon planktonic populations was
      very low despite shared selection for growth under low-carbon conditions,
      suggesting that evolution in low-carbon environments may generate stronger trade
      offs between biofilm and planktonic modes of growth. For all environments, a
      population's fitness in a particular environment was positively correlated with
      the genetic similarity between that population and the populations that evolved
      in that particular environment. Although genetic similarity was low between low
      carbon environments, overall, evolution in similar environments led to higher
      levels of genetic parallelism and that genetic parallelism, in turn, was
      correlated with fitness in a particular environment.

PMID- 30283688
TI  - The effects of haploid selection on Y chromosome evolution in two closely related
      dioecious plants.
AB  - The evolution of sex chromosomes is usually considered to be driven by sexually
      antagonistic selection in the diploid phase. However, selection during the
      haploid gametic phase of the lifecycle has recently received theoretical
      attention as possibly playing a central role in sex chromosome evolution,
      especially in plants where gene expression in the haploid phase is extensive. In
      particular, male-specific haploid selection might favor the linkage of pollen
      beneficial alleles to male sex determining regions on incipient Y chromosomes.
      This linkage might then allow such alleles to further specialize for the haploid
      phase. Purifying haploid selection is also expected to slow the degeneration of Y
      linked genes expressed in the haploid phase. Here, we examine the evolution of
      gene expression in flower buds and pollen of two species of Rumex to test for
      signatures of haploid selection acting during plant sex chromosome evolution. We
      find that genes with high ancestral pollen expression bias occur more often on
      sex chromosomes than autosomes and that genes on the Y chromosome are more likely
      to become enriched for pollen expression bias. We also find that genes with low
      expression in pollen are more likely to be lost from the Y chromosome. Our
      results suggest that sex-specific haploid selection during the gametophytic stage
      of the lifecycle may be a major contributor to several features of plant sex
      chromosome evolution.

PMID- 30283689
TI  - Timing malaria transmission with mosquito fluctuations.
AB  - Temporal variations in the activity of arthropod vectors can dramatically affect
      the epidemiology and evolution of vector-borne pathogens. Here, we explore the
      "Hawking hypothesis", which states that these pathogens may evolve the ability to
      time investment in transmission to match the activity of their vectors. First, we
      use a theoretical model to identify the conditions promoting the evolution of
      time-varying transmission strategies in pathogens. Second, we experimentally test
      the "Hawking hypothesis" by monitoring the within-host dynamics of Plasmodium
      relictum throughout the acute and the chronic phases of the bird infection. We
      detect a periodic increase of parasitemia and mosquito infection in the late
      afternoon that coincides with an increase in the biting activity of its natural
      vector. We also detect a positive effect of mosquito bites on Plasmodium
      replication in the birds both in the acute and in the chronic phases of the
      infection. This study highlights that Plasmodium parasites use two different
      strategies to increase the match between transmission potential and vector
      availability. We discuss the adaptive nature of these unconditional and plastic
      transmission strategies with respect to the time scale and the predictability of
      the fluctuations in the activity of the vector.

PMID- 30283690
TI  - Decomposing parasite fitness reveals the basis of specialization in a two-host,
      two-parasite system.
AB  - The ecological specialization of parasites-whether they can obtain high fitness
      on very few or very many different host species-is a determining feature of their
      ecology. In order to properly assess specialization, it is imperative to measure
      parasite fitness across host species; to understand its origins, fitness must be
      decomposed into the underlying traits. Despite the omnipresence of parasites with
      multiple hosts, very few studies assess and decompose their specialization in
      this way. To bridge this gap, we quantified the infectivity, virulence, and
      transmission rate of two parasites, the horizontally transmitted microsporidians
      Anostracospora rigaudi and Enterocytospora artemiae, in their natural hosts, the
      brine shrimp Artemia parthenogenetica and Artemia franciscana. Our results
      demonstrate that each parasite performs well on one of the two host species (A.
      rigaudi on A. parthenogenetica, and E. artemiae on A. franciscana), and poorly on
      the other. This partial specialization is driven by high infectivity and
      transmission rates in the preferred host, and is associated with maladaptive
      virulence and large costs of resistance in the other. Our study represents a rare
      empirical contribution to the study of parasite evolution in multihost systems,
      highlighting the negative effects of under- and overexploitation when adapting to
      multiple hosts.

PMID- 30283691
TI  - Large-effect mutations generate trade-off between predatory and locomotor ability
      during arms race coevolution with deadly prey.
AB  - Adaptive evolution in response to one selective challenge may disrupt other
      important aspects of performance. Such evolutionary trade-offs are predicted to
      arise in the process of local adaptation, but it is unclear if these phenotypic
      compromises result from the antagonistic effects of simple amino acid
      substitutions. We tested for trade-offs associated with beneficial mutations that
      confer tetrodotoxin (TTX) resistance in the voltage-gated sodium channel (NaV1.4)
      in skeletal muscle of the common garter snake (Thamnophis sirtalis). Separate
      lineages in California and the Pacific Northwest independently evolved TTX
      resistant changes to the pore of NaV1.4 as a result of arms race coevolution with
      toxic prey, newts of the genus Taricha. Snakes from the California lineage that
      were homozygous for an allele known to confer large increases in toxin resistance
      (NaV1.4LVNV) had significantly reduced crawl speed compared to individuals with
      the ancestral TTX-sensitive channel. Heterologous expression of native snake
      NaV1.4 proteins demonstrated that the same NaV1.4LVNV allele confers a dramatic
      increase in TTX resistance and a correlated decrease in overall channel
      excitability. Our results suggest the same mutations that accumulate during arms
      race coevolution and beneficially interfere with toxin-binding also cause changes
      in electrophysiological function of the channel that may affect organismal
      performance. This trade-off was only evident in the predator lineage where
      coevolution has led to the most extreme resistance phenotype, determined by four
      critical amino acid substitutions. If these biophysical changes also translate to
      a fitness cost-for example, through the inability of T. sirtalis to quickly
      escape predators-then pleiotropy at this single locus could contribute to
      observed variation in levels of TTX resistance across the mosaic landscape of
      coevolution.

PMID- 30283692
TI  - Evolutionary origins of vocal mimicry in songbirds.
AB  - Vocal learning is an important behavior in oscines (songbirds). Some songbird
      species learn heterospecific sounds as well as conspecific vocalizations. The
      emergence of vocal mimicry is necessarily tied to the evolution of vocal
      learning, as mimicry requires the ability to acquire sounds through learning. As
      such, tracking the evolutionary origins of vocal mimicry may provide insights
      into the causes of variation in song learning programs among songbirds. We
      compiled a database of known vocal mimics that comprised 339 species from 43
      families. We then traced the evolutionary history of vocal mimicry across the
      avian phylogeny using ancestral trait reconstruction on a dataset of oscine
      passerines for which vocalizations have been described. We found that the common
      ancestor to oscines was unlikely to mimic sounds, suggesting that song learning
      evolved with mechanisms to constrain learning to conspecific models. Mimicry then
      evolved repeatedly within the songbird clade, either through relaxation of
      constraints on conspecific learning or through selection for active vocal
      mimicry. Vocal mimicry is likely ancestral in only a handful of clades, and we
      detect many instances of independent origins of mimicry. Our analysis underscores
      the liability of vocal mimicry in songbirds, and highlights the evolutionary
      flexibility of song learning mechanisms.

PMID- 30283693
TI  - Dramatic evolution of body length due to postembryonic changes in cell size in a
      newly discovered close relative of Caenorhabditis elegans.
AB  - Understanding morphological diversity-and morphological constraint-has been a
      central question in evolutionary biology since its inception. Nematodes of the
      genus Caenorhabditis, which contains the well-studied model organism C. elegans,
      display remarkable morphological consistency in the face of extensive genetic
      divergence. Here, we provide a description of the broad developmental patterns of
      a newly discovered species, C. sp. 34, which was isolated from fresh figs in
      Okinawa and which is among the closest known relatives of C. elegans. C. sp. 34
      displays an extremely large body size; it can grow to be nearly twice as long as
      C. elegans and all other known members of the genus. Observations of the timing
      of developmental milestones reveal that C. sp. 34 develops about twice as slowly
      as C. elegans. Measurements of embryonic and larval size show that the size
      difference between C. sp. 34 and C. elegans is largely due to postembryonic
      events, particularly during the transition from larval to adult stages. This
      difference in size is not attributable to differences in germ line chromosome
      number or the number of somatic cells. The overall difference in body size is
      therefore largely attributable to changes in cell size via increased cytoplasmic
      volume. Because of its close relationship to C. elegans, the distinctness of C.
      sp. 34 provides an ideal system for the detailed analysis of evolutionary
      diversification. The context of over 40 years of C. elegans developmental
      genetics also reveals clues into how natural selection and developmental
      constraint act jointly to promote patterns of morphological stasis and divergence
      in this group.

PMID- 30283694
TI  - Nonclonal coloniality: Genetically chimeric colonies through fusion of sexually
      produced polyps in the hydrozoan Ectopleura larynx.
AB  - Hydrozoans typically develop colonies through asexual budding of polyps. Although
      colonies of Ectopleura are similar to other hydrozoans in that they consist of
      multiple polyps physically connected through continuous epithelia and shared
      gastrovascular cavity, Ectopleura larynx does not asexually bud polyps
      indeterminately. Instead, after an initial phase of limited budding in a young
      colony, E. larynx achieves its large colony size through the aggregation and
      fusion of sexually (nonclonally) produced polyps. The apparent chimerism within a
      physiologically integrated colony presents a potential source of conflict between
      distinct genetic lineages, which may vary in their ability to access the
      germline. To determine the extent to which the potential for genetic conflict
      exists, we characterized the types of genetic relationships between polyps within
      colonies, using a RAD-Seq approach. Our results indicate that E. larynx colonies
      are indeed comprised of polyps that are clones and sexually reproduced siblings
      and offspring, consistent with their life history. In addition, we found that
      colonies also contain polyps that are genetically unrelated, and that estimates
      of genome-wide relatedness suggests a potential for conflict within a colony.
      Taken together, our data suggest that there are distinct categories of
      relationships in colonies of E. larynx, likely achieved through a range of
      processes including budding, regeneration, and fusion of progeny and unrelated
      polyps, with the possibility for a genetic conflict resolution mechanism.
      Together these processes contribute to the reevolution of the ecologically
      important trait of coloniality in E. larynx.

PMID- 30283695
TI  - Ageing with a silver-spoon: A meta-analysis of the effect of developmental
      environment on senescence.
AB  - What determines variation between individuals in how they senesce, and are
      environmental conditions experienced during development relevant to late-life
      performance? We report a meta-analysis of studies of wild populations to
      determine how the quality of the environment experienced during development
      affects rates of survival and reproductive senescence. From studies of 14 bird or
      mammal species, we calculated effect sizes for the interaction between the
      effects of environmental quality during development and age in predicting
      survival (N = 18) or reproduction (N = 30) over time in late life. We found no
      evidence that developmental environment affected rates of survival senescence
      (betamean = -1.2 * 10-4 +/- 0.022SE). However, a better developmental environment
      was associated with slower rates of reproductive senescence in late life
      (betamean = 0.062 +/- 0.023SE), indicating a small, but significant, "silver
      spoon" effect of early-life conditions that persisted through to late life. Our
      results illustrate how the effects of environmental conditions during development
      can persist throughout life, and indicate one possible cause of phenotypic
      plasticity in senescence.

PMID- 30283696
TI  - Coadapted genomes and selection on hybrids: Fisher's geometric model explains a
      variety of empirical patterns.
AB  - Natural selection plays a variety of roles in hybridization, speciation, and
      admixture. Most research has focused on two extreme cases: crosses between
      closely related inbred lines, where hybrids are fitter than their parents, or
      crosses between effectively isolated species, where hybrids suffer severe
      breakdown. But many natural populations must fall into intermediate regimes, with
      multiple types of gene interaction, and these are more difficult to study. Here,
      we develop a simple fitness landscape model, and show that it naturally
      interpolates between previous modeling approaches, which were designed for the
      extreme cases, and invoke either mildly deleterious recessives, or discrete
      hybrid incompatibilities. Our model yields several new predictions, which we test
      with genomic data from Mytilus mussels, and published data from plants (Zea,
      Populus, and Senecio) and animals (Mus, Teleogryllus, and Drosophila). The
      predictions are generally supported, and the model explains a number of
      surprising empirical patterns. Our approach enables novel and complementary uses
      of genome-wide datasets, which do not depend on identifying outlier loci, or
      "speciation genes" with anomalous effects. Given its simplicity and flexibility,
      and its predictive successes with a wide range of data, the approach should be
      readily extendable to other outstanding questions in the study of hybridization.

PMID- 30283697
TI  - Positive and balancing selection on SLC18A1 gene associated with psychiatric
      disorders and human-unique personality traits.
AB  - Maintenance of genetic variants susceptible to psychiatric disorders is one of
      the intriguing evolutionary enigmas. The present study detects three psychiatric
      disorder-relevant genes (CLSTN2, FAT1, and SLC18A1) that have been under positive
      selection during the human evolution. In particular, SLC18A1 (vesicular monoamine
      transporter 1; VMAT1) gene has a human-unique variant (rs1390938, Thr136Ile),
      which is associated with bipolar disorders and/or the anxiety-related personality
      traits. 136Ile shows relatively high (20-61%) frequency in non-African
      populations, and Tajima's D reports a significant peak around the Thr136Ile site,
      suggesting that this polymorphism has been positively maintained by balancing
      selection in non-African populations. Moreover, Coalescent simulations predict
      that 136Ile originated around 100,000 years ago, the time being generally
      associated with the Out-of-Africa migration of modern humans. Our study sheds new
      light on a gene in monoamine pathway as a strong candidate contributing to human
      unique psychological traits.

PMID- 30283698
TI  - Lineages evolved under stronger sexual selection show superior ability to invade
      conspecific competitor populations.
AB  - Despite limitations on offspring production, almost all multicellular species use
      sex to reproduce. Sex gives rise to sexual selection, a widespread force
      operating through competition and choice within reproduction, however, it remains
      unclear whether sexual selection is beneficial for total lineage fitness, or if
      it acts as a constraint. Sexual selection could be a positive force because of
      selection on improved individual condition and purging of mutation load, summing
      into lineages with superior fitness. On the other hand, sexual selection could
      negate potential net fitness through the actions of sexual conflict, or because
      of tensions between investment in sexually selected and naturally selected
      traits. Here, we explore these ideas using a multigenerational invasion challenge
      to measure consequences of sexual selection for the overall net fitness of a
      lineage. After applying experimental evolution under strong versus weak regimes
      of sexual selection for 77 generations with the flour beetle Tribolium castaneum,
      we measured the overall ability of introductions from either regime to invade
      into conspecific competitor populations across eight generations. Results showed
      that populations from stronger sexual selection backgrounds had superior net
      fitness, invading more rapidly and completely than counterparts from weak sexual
      selection backgrounds. Despite comprising only 10% of each population at the
      start of the invasion experiment, colonizations from strong sexual selection
      histories eventually achieved near-total introgression, almost completely
      eliminating the original competitor genotype. Population genetic simulations
      using the design and parameters of our experiment indicate that this invasion
      superiority could be explained if strong sexual selection had improved both
      juvenile and adult fitness, in both sexes. Using a combination of empirical and
      modeling approaches, our findings therefore reveal positive and wide-reaching
      impacts of sexual selection for net population fitness when facing the broad
      challenge of invading competitor populations across multiple generations.

PMID- 30283699
TI  - Don't throw out the sympatric speciation with the crater lake water: fine-scale
      investigation of introgression provides equivocal support for causal role of
      secondary gene flow in one of the clearest examples of sympatric speciation.
AB  - Genomic data has revealed complex histories of colonization and repeated gene
      flow previously unrecognized in some of the most celebrated examples of sympatric
      speciation and radiation. However, much of the evidence for secondary gene flow
      into these radiations comes from summary statistics calculated from sparse
      genomic sampling without knowledge of which specific genomic regions
      introgressed. This tells us little about how gene flow potentially influenced
      sympatric diversification. Here, we investigated whole genomes of Barombi Mbo
      crater lake cichlids for fine-scale patterns of introgression with neighboring
      riverine cichlid populations. We found evidence of secondary gene flow into the
      radiation scattered across <0.24% of the genome; however, from our analyses, it
      is not clear if the functional diversity in these regions contributed to the
      ecological, sexual, and morphological diversity found in the lake. Unlike similar
      studies, we found no obvious candidate genes for adaptive introgression and we
      cannot rule out that secondary gene flow was predominantly neutral with respect
      to the diversification process. We also found evidence for differential
      assortment of ancestral polymorphisms found in riverine populations between
      sympatric sister species, suggesting the presence of an ancestral hybrid swarm.
      Although the history of gene flow and colonization is more complicated than
      previously assumed, the lack of compelling evidence for secondary gene flow's
      role in species diversification suggests that we should not yet rule out one of
      the most celebrated examples of sympatric speciation in nature without a more
      thorough investigation of the timing and functional role of each introgressed
      region.

PMID- 30283700
TI  - Development of metastatic brain disease involves progression through lung
      metastases in EGFR mutated non-small cell lung cancer.
AB  - Lung cancer is often classified by the presence of oncogenic drivers, such as
      epidermal growth factor receptor (EGFR), rather than patterns of anatomical
      distribution. While metastatic spread may seem a random and unpredictable
      process, we explored the possibility of using its quantifiable nature as a
      measure of describing and comparing different subsets of disease. We constructed
      a database of 664 non-small cell lung cancer (NSCLC) patients treated at the
      University of Southern California Norris Comprehensive Cancer Center and the Los
      Angeles County Medical Center. Markov mathematical modeling was employed to
      assess metastatic sites in a spatiotemporal manner through every time point in
      progression of disease. Our findings identified a preferential pattern of primary
      lung disease progressing through lung metastases to the brain amongst EGFR
      mutated (EGFR m) NSCLC patients, with exon 19 deletions or exon 21 L858R
      mutations, as compared to EGFR wild type (EGFR wt). The brain was classified as
      an anatomic "sponge", with a higher ratio of incoming to outgoing spread, for
      EGFR m NSCLC. Bone metastases were more commonly identified in EGFR wt patients.
      Our study supports a link between the anatomical and molecular characterization
      of lung metastatic cancer. Improved understanding of the differential biology
      that drives discordant patterns of anatomic spread, based on genotype specific
      profiling, has the potential to improve personalized oncologic care.

PMID- 30283701
TI  - A Systematic Review on Prevention and Treatment of Nipple Pain and Fissure: Are
      They Curable?
AB  - Averagely 80% to 90% of breastfeeding women experience the nipple pain and
      fissures. The important factor for successful breastfeeding is to treat this
      problem. This study has done as a review with the aim of analysis of the clinical
      trials in the field of the prevention and treatment of the nipple fissures and
      pain due to the importance of breastfeeding. For this purpose, the key words of
      sore, nipples, fissure, trauma, wound, prevention, treatment, therapeutics,
      therapy, clinical trial, breastfeeding and their Persian synonyms and all of
      their possible combinations were searched in the national databases: SID and Iran
      Medex and Magiran, and in the international databases: PubMed, Scopus, Medline,
      Science direct by May 2017. The Jadad criterion was used to assess the quality of
      the articles and the articles with a score of 3 or more were included in this
      study. Finally, 48 clinical trials were reviewed that 17 of them (sample size
      1801) scored 3 or more based on the Jadad criterion. Seven articles were also in
      the non- drug treatment group (sample size 491) and 2 articles in the drug
      treatment group (sample size 337) and 8 articles in the herbal treatment group
      (sample size 973).The results show that menthol and warm water compress as well
      as teaching the correct breastfeeding methods are effective treatments to prevent
      and treat the nipple pain and fissures. Moreover, applying the herbal medicine
      for prevention and treatment of the issues raised from breastfeeding may have
      beneficial such as Aloe vera, Portulaca olearacea. However, more studies with a
      great methodology are necessary to obtain more accurate evidence.

PMID- 30283702
TI  - Efficacy and Safety of Miniscalpel Acupuncture on Knee Osteoarthritis: - A
      randomized controlled pilot trial.
AB  - Objectives: We investigated the efficacy and safety of miniscalpel acupuncture
      (MA) for knee osteoarthritis (KOA) in an assessor-blinded randomized controlled
      pilot trial; this would provide information for a large-scale randomized
      controlled trial. Methods: Participants (n = 24) were recruited and randomly
      allocated to the MA group (experimental) or acupuncture group (control). The MA
      group received treatment once a week for 3 weeks (total of 3 treatments), while
      the acupuncture group received treatment two times per week for 3 weeks (total of
      6 treatments). The primary outcome was pain as assessed by a visual analogue
      scale (VAS). The secondary outcomes (intensity of current pain, stiffness, and
      physical function) were assessed using the short-form McGill Pain Questionnaire
      (SF-MPQ) and Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC). Assessments were performed at baseline, 1, 2, and 3 during treatment and
      at week 5 (2 weeks after the end of treatment). Results: Of the 24 participants,
      23 completed the study. Both groups showed significant improvements in VAS, SF
      MPQ, and WOMAC. However, there were no significant differences between the MA and
      acupuncture groups. No serious adverse event occurred and blood test results were
      within normal limits. Conclusion: Our results suggest that although both MA and
      acupuncture provide similar effects with regard to pain control in patients with
      KOA, MA may be more effective in providing pain relief because the same relief
      was obtained with fewer treatments. A large-scale clinical study is warranted to
      further clarify these findings.

PMID- 30283703
TI  - Teucrium polium L. Improved Heart Function and Inhibited Myocardial Apoptosis in
      Isolated Rat Heart Following Ischemia-Reperfusion Injury.
AB  - Objectives: Myocardial reperfusion is the only logical cure for ischemic heart
      disease. However, ischemic-reperfusion (I/R) injury is one of the underlying
      factors facilitating and accelerating the apoptosis in the myocardium. This study
      set to investigate the impact of Teucrium polium (TP) hydro-alcoholic extract on
      I/R induced apoptosis in the isolated rat heart. Methods: Isolated rat hearts
      were classified into six groups. The control samples were subjected to 80 min of
      perfusion with Krebs-Henseleit bicarbonate (KHB) buffer; in control-ischemia
      group, after primary perfusion (20 min) the hearts were exposed to global
      ischemia (20 min) and reperfusion (40 min). Pretreated groups were perfused with
      500 MUM of vitamin C and various TP concentrations (0.5, 1, 2 mg/ml) for 20 min,
      and then the hearts were exposed to ischemia and reperfusion for 20 min and 40
      min, respectively. Cardiodynamic parameters including rate pressure product
      (RPP), heart rate (HR), the maximum up/down rate of left ventricular pressure (+/
      dp/dt), left ventricular developed pressure (LVDP), and coronary artery flow (CF)
      were achieved from Lab Chart software data. The Bax and BCl-2 gene expressions
      were measured in heart samples. Results: Hearts treated with TP extract and vit C
      represented a meaningful improvement in cardiac contractile function and CF. The
      overexpression of Bcl-2, downregulation of Bax, and improvement of apoptotic
      index (Bax/Bcl-2) were observed in pretreated TP extract and vit C hearts.
      Conclusion: The TP extract was found to ameliorate the cardiac function in the
      reperfused myocardium. Also, it can hinder apoptotic pathways causing
      cardioprotection.

PMID- 30283704
TI  - Ethanol and Methanol Concentration in Commonly Used Brands of Ma-al-shaeer in
      Iran: Estimation of Dietary Intakes and Risk Assessment.
AB  - Objectives: Ma-al-shaeer is a popular beverage in Islamic countries. The aim of
      this study was to determine the concentrations of methanol and ethanol in most
      consumed brands of Ma-al-shaeer in Iran. Methods: Eighty-one Ma-al-shaeer samples
      which commonly used in Iran were provided. Methanol and ethanol contents were
      determined by gas chromatography with flame ionization detector. Results: The
      mean methanol concentrations in Iranian and foreign brands was 129.84+/-205.38
      mg/L and 110.157+/-135.98 mg/L, respectively. Although mean ethanol contents of
      Iranian brands was 1.2+/-2.41 mg/L, ethanol level in foreign ones was lower than
      LOQ. Conclusion: Since the most Ma-al-shaeer brands had methanol pollution at
      different levels establishment of a definitive relationship between the methanol
      content and toxicological effects seem to be vital. EDI of methanol for Iranian
      people through consumption of Ma-al-shaeer was determined 0.023mg/kg bw/day.

PMID- 30283705
TI  - Auraptene Inhibits Migration and Invasion of Cervical and Ovarian Cancer Cells by
      Repression of Matrix Metalloproteinasas 2 and 9 Activity.
AB  - Objectives: Auraptene, a natural citrus coumarin, found in plants of Rutaceae and
      Apiaceae families. In this study, we investigated the effects of auraptene on
      tumor migration, invasion and matrix metalloproteinase (MMP)-2 and -9 enzymes
      activity. Methods: The effects of auraptene on the viability of A2780 and Hela
      cell lines was evaluated by MTT assay. Wound healing migration assay and Boyden
      chamber assay were determined the effect of auraptene on migration and cell
      invasion, respectively. MMP-2 and MMP-9 activities were analyzed by gelatin
      zymography assay. Results: Auraptene reduced A2780 cell viability. The results
      showed that auraptene inhibited in vitro migration and invasion of both cells.
      Furthermore, cell invasion ability suppressed at 100MUM auraptene in Hela cells
      and at 25, 50MUM in A2780 cell line. Gelatin zymography showed that for Hela cell
      line, auraptene suppressed MMP-2 enzymatic activity in all concentrations and for
      MMP-9 at a concentration between 12.5 to 100MUM in A2780 cell line. Conclusion:
      Auraptene inhibited migration and invasion of human cervical and ovarian cancer
      cells in vitro by possibly inhibitory effects on MMP-2 and MMP-9 activity.

PMID- 30283706
TI  - Quercus Brantii Lindl. Vaginal Douche Versus Clotrimazole on Vaginal Candidiasis:
      A Randomized Clinical Trial.
AB  - Objectives: Vaginal Candidiasis with an approximate prevalence of 30% is the
      second cause of vaginal infections. Antifungal azole is the first treatment for
      Vaginal Candidiasis; however, some side effects have been reported for this
      chemical medicine. Based on the antifungal activity of Inner Stratum of Quercus
      Brantii (Q. Brantii), the aim of our study was to compare the effects of vaginal
      douche of Q. Brantii extract and clotrimazole on vaginal candidiasis symptoms
      before and after the treatments, in women. Methods: 89 non-pregnant women with
      positive KOH test which is capable of identifying the presence of hyphae and
      mycelium by adding KOH (10%), and a positive vaginal candidiasis culture were
      randomly divided into two experimental groups, using permuted block randomization
      method. One group received clotrimazole vaginal cream (1%) and the other group
      received vaginal douche of Q. Brantii extract. Groups were treated for 7 days and
      KOH tests and cultures were evaluated again. Data were analyzed via chi-square
      and independent t-test, using SPSS software. Results: According to the results,
      there were no significant differences between experimental groups for demographic
      characteristics like age (p=0.403), BMI (p=0.911), educational levels (p=0.862)
      and contraceptive methods (p=0.702). Moreover, significant differences were seen
      in vaginal discharge between the groups after the treatments (P=0.043).
      Conclusion: The results suggested that the therapeutic effect of vaginal douche
      of Q. Brantii extract was approximately similar to that of clotrimazole vaginal
      cream.

PMID- 30283707
TI  - Statues and Improvement of Electronic Medical Record System in Traditional Korean
      Medicine.
AB  - Objectives: The study was to survey use of electronic medical records in subjects
      of Korean medicine doctors working for Korean medicine organizations and to
      contemplate ways to develop utilization of electronic medical records. Methods:
      On August 2017, it conducted online self-reported survey on subjects of Korean
      medicine doctors at Korean hospitals and clinics who agreed to participate in the
      study. A total 40 doctors in hospital and 279 doctors in clinic were included.
      The surveyed contents include kinds of electronic chart, reason for not using
      electronic medical records and problems with creation of medical records.
      Results: It finds that 100% of those working at Korean medicine hospitals and
      86.4% of those at Korean medicine clinics have used electronic medical records.
      Subjects answered the biggest reason for not using electronic medical records was
      inconvenience. The most serious problems with creation of electronic medical
      records at Korean medicine organizations found in the study include there was no
      method of creation of medical records and no standardized terminology for use in
      electronic medical records. Conclusion: For utilization of electronic medical
      records at Korean medicine organizations, standardization of terminology,
      development of EMR in favour of its users and development of strategy that
      motivates use of EMR are required.

PMID- 30283708
TI  - Orthogonal Stimulus-Response as a Tool to Formulate Traditional Chinese Medicinal
      Herbal Combination: - New Scientific-Based TCM Herbal Formulating Method.
AB  - Objectives: There is an increasing number of complex diseases that are
      progressively more difficult to be controlled using the conventional "single
      compound, single target" approach as demonstrated in our current modern drug
      development. TCM might be the new cornerstone of treatment alternative when the
      current treatment option is no longer as effective or that we have exhausted it
      as an option. Orthogonal stimulus-response compatibility group study is one of
      the most frequently employed formulas to produce optimal herbal combination for
      treatment of multi-syndromic diseases. This approach could solve the relatively
      low efficacy single drug therapy usage and chronic adverse effects caused by long
      terms administration of drugs that has been reported in the field of pharmacology
      and medicine. Methods: The present review was based on the Science Direct
      database search for those related to the TCM and the development of
      antihypertensive TCM herbal combination using orthogonal stimulus-response
      compatibility group studies approach. Results: Recent studies have demonstrated
      that the orthogonal stimulus-response compatibility group study approach was most
      frequently used to formulate TCM herbal combination based on the TCM principles
      upon the selection of herbs, and the resulting formulated TCM formula exhibited
      desired outcomes in treating one of global concerned complex multi-syndromic
      diseases, the hypertension. These promising therapeutic effects were claimed to
      have been attributed by the holistic signaling mechanism pathways employed by the
      crude combination of herbs. Conclusion: The present review could serve as a guide
      and prove the feasibility of TCM principles to be used for future pharmacological
      drug research development.

PMID- 30283709
TI  - Acinar cell injury induced by inadequate unfolded protein response in acute
      pancreatitis.
AB  - Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue
      initiated in injured acinar cells. Severe AP remains a significant challenge due
      to the lack of effective treatment. The widely-accepted autodigestion theory of
      AP is now facing challenges, since inhibiting protease activation has negligible
      effectiveness for AP treatment despite numerous efforts. Furthermore,
      accumulating evidence supports a new concept that malfunction of a self
      protective mechanism, the unfolded protein response (UPR), is the driving force
      behind the pathogenesis of AP. The UPR is induced by endoplasmic reticulum (ER)
      stress, a disturbance frequently found in acinar cells, to prevent the
      aggravation of ER stress that can otherwise lead to cell injury. In addition, the
      UPR's signaling pathways control NFkappaB activation and autophagy flux, and
      these dysregulations cause acinar cell inflammatory injury in AP, but with poorly
      understood mechanisms. We therefore summarize the protective role of the UPR in
      AP, propose mechanistic models of how inadequate UPR could promote NFkappaB's pro
      inflammatory activity and impair autophagy's protective function in acinar cells,
      and discuss its relevance to current AP treatment. We hope that insight provided
      in this review will help facilitate the research and management of AP.

PMID- 30283710
TI  - Gut microbiome profiling and colorectal cancer in African Americans and Caucasian
      Americans.
AB  - AIM: To determine whether and to what extent the gut microbiome is involved in
      regulating racial disparity in colorectal cancer (CRC). METHODS: All patients
      were recruited and experiments were performed in accordance with the relevant
      guidelines and regulations by the Institutional Review Boards (IRB), committees
      of the John D. Dingell VAMC and Wayne State University guidelines. African
      American (AA) and Caucasian American (CA) patients were scheduled for an
      outpatient screening for colonoscopy, and no active malignancy volunteer patients
      were doubly consented, initially by the gastroenterologist and later by the study
      coordinator, for participation in the study. The gut microbial communities in
      colonic effluents from AAs and CAs were examined using 16sRNA profiling, and
      bacterial identifications were validated by performing SYBR-based Real Time PCR.
      For metagenomic analysis to characterize the microbial communities, multiple
      software/tools were used, including Metastats and R statistical software.
      RESULTS: It is generally accepted that the incidence and mortality of CRC is
      higher in AAs than in CAs. However, the reason for this disparity is not well
      understood. We hypothesize that the gut microbiome plays a role in regulating
      this disparity. Indeed, we found significant differences in species richness and
      diversity between AAs and CAs. Bacteroidetes was more abundant in AAs than in
      CAs. In particular, the pro-inflammatory bacteria Fusobacterium nucleatum and
      Enterobacter species were significantly higher in AAs, whereas probiotic
      Akkermansia muciniphila and Bifidobacterium were higher in CAs. The polyphyletic
      Clostridia class showed a divergent pattern, with Clostridium XI elevated in AAs,
      and Clostridium IV, known for its beneficial function, higher in CAs. Lastly, the
      AA group had decreased microbial diversity overall in comparison to the CA group.
      In summary, there were significant differences in pro-inflammatory bacteria and
      microbial diversity between AA and CA, which may help explain the CRC disparity
      between groups. CONCLUSION: Our current investigation, for the first time,
      demonstrates microbial dysbiosis between AAs and CAs, which could contribute to
      the racial disparity of CRC.

PMID- 30283711
TI  - Current State and Future of Biologic Therapies in the Treatment of Asthma in
      Children.
AB  - There is increasing recognition of phenotypic variability in pediatric asthma,
      providing the opportunity for a more personalized approach to therapy.
      Increasingly biologic therapies, in particular those targeting the "allergic" (or
      T helper 2) pathway, are being considered for children with severe asthma.
      However, there is a great deal of variability in the extent these biologic
      therapies have been studied in children, as well as efficacy of results thus far.
      The goal of this article is to review the mechanism of action, efficacy, and
      potential predictive and monitoring biomarkers of the biologic medications
      focusing on the pediatric population, in an effort to establish a more
      personalized approach to asthma in the pediatric population for the 21st century.

PMID- 30283713
TI  - Allergic Diseases and Immune-Mediated Food Disorders in Pediatric Acute-Onset
      Neuropsychiatric Syndrome.
AB  - Background: The prevalence and impact of allergic and immune-mediated food
      disorders in pediatric acute-onset neuropsychiatric syndrome (PANS) are mostly
      unknown. Objective: We sought to explore the prevalence of atopic dermatitis
      (AD), asthma, allergic rhinitis (AR), IgE-mediated food allergies (FAs), and
      other immune-mediated food disorders requiring food avoidance in patients with
      PANS. In addition, to further understand the extent of food restriction in this
      population, we investigated the empiric use of dietary measures to improve PANS
      symptoms. Methods: Pediatric patients in a PANS Clinic and Research Program were
      given surveys regarding their caregiver burdens, allergic and food-related
      medical history, and whether food elimination resulted in perception of
      improvement of PANS symptoms. A review of health records was conducted to confirm
      that all responses in the survey were concordant with documentation of each
      patient's medical chart. Results: Sixty-nine (ages 4-20 years) of 80 subjects who
      fulfilled PANS criteria completed the surveys. Thirteen (18.8%) had AD, 11
      (15.9%) asthma, 33 (47.8%) AR, 11 (15.9%) FA, 1 (1.4%) eosinophilic
      gastrointestinal disorders, 1 (1.4%) food protein-induced enterocolitis syndrome,
      3 (4.3%) milk protein-induced proctocolitis syndrome, and 3 (4.3%) celiac
      disease. Thirty subjects (43.5%) avoided foods due to PANS; elimination of gluten
      and dairy was most common and was associated with perceived improvement of PANS
      symptoms (by parents). This perceived improvement was not confirmed with
      objective data. Conclusions: The prevalence of allergic and immune-mediated food
      disorders in PANS is similar to the general population as reported in the
      literature, with the exception of AR that appears to be more prevalent in our
      PANS cohort. More research will be required to establish whether diet or
      allergies influence PANS symptoms.

PMID- 30283712
TI  - Perception of Pulmonary Function in Children with Asthma and Cystic Fibrosis.
AB  - Background: Under-perception of pulmonary dysfunction may delay appropriate
      treatment, while over-perception may result in unnecessary treatments.
      Objectives: To evaluate the ability of patients with asthma or cystic fibrosis
      and their subspecialty caregivers to assess changes in lung function based on
      their subjective clinical impressions. Methods: Patients were asked to
      qualitatively describe how they felt compared to their prior visit
      (same/better/worse) and to quantitatively estimate their forced expiratory volume
      in 1 s (FEV1) after being reminded of their FEV1 at the prior visit. Providers
      made similar estimates based on history and physical examination and knowledge of
      prior FEV1. After adjusting for relevant clinical covariates, lung function
      estimates were categorized as accurate (+/-5% of measured FEV1), overestimated
      (>5% above measured), and underestimated (>5% below measured). Results: One
      hundred nine patients estimated FEV1 on 179 occasions. Concordance between
      patient qualitative assessment and FEV1-based categories was low (kappa = 0.08);
      44% of patients reported feeling better than the FEV1-based category showed.
      Quantitatively, 56% of patient estimates were accurate, 18% were underestimated,
      and 26% overestimated; accuracy improved with age (odds ratio = 1.16, P = 0.01).
      Concordance between provider qualitative assessments and FEV1-based category was
      moderate (kappa = 0.35); about 19% said their patient looked better than the FEV1
      based category showed. Quantitatively, 65% of provider estimates were accurate,
      16% were underestimated, and 19% were overestimated; accuracy improved with years
      of experience. Conclusions: Patients' and providers' perceptions of lung function
      were low to moderately accurate. Relying on subjective impression may place
      patients at risk for unnecessary treatments or increased morbidity. These
      findings highlight the importance of objective lung function assessment.

PMID- 30283715
TI  - One burr-hole craniotomy: Modified presigmoid approach in Helsinki Neurosurgery.
AB  - Background: In this video abstract, we present a one burr-hole craniotomy for a
      modified presigmoid approach developed in Helsinki Neurosurgery to access the
      space extended to both middle and posterior fossa. Thus, indications for this
      approach are lesions that extend to both middle and posterior fossa, petroclival
      tumors, basilar tip aneurysms located extremely low below the posterior clinoid
      process, trunk basilar aneurysms, and bypass procedures from the P2 segment of
      the posterior cerebral artery. The procedure is composed by three stages: a
      temporal and presigmoid craniotomy, a partial petromastoidectomy, and the dura
      opening with section of the superior petrosal sinus (SPS) and the tentorium. Even
      though some risks related to the opening of the mastoid cells or cut of the SPS
      may exist, benefits of this optimized craniotomy are higher compared with the
      complications. Case Description: The patient with a giant petroclival meningioma
      is placed in park bench position and spinal drainage is inserted. Skin incision
      starts in front of the ear curve going to 1 inch behind the mastoid line. Strong
      retraction with hooks keeps a clean space for the craniotomy. Hemostatic Raney
      clips are placed at the superior border of the skin flap. A burr-hole is made at
      the most cranial part of the temporal bone. After the detachment of the dura with
      long flexible blunt dissectors, the craniotomy is performed to expose the sigmoid
      sinus, the SPS and the dura of the inferior temporal lobe, and the floor of the
      middle fossa. Aiming to access the posterior fossa by a presigmoid route, a
      partial petromastoidectomy is performed preserving the semicircular canals. Few
      drill holes are made for tack-up sutures. Once we properly reach the dura of the
      middle and posterior fossa, dura of the temporal lobe and later, the presigmoid
      dura are opened joining at the level of the SPS. The SPS, which is running over
      the petrous bone between the posterior and the middle fossa, is coagulated,
      ligated, and cut. After SPS is sectioned, the tentorium is cut anterior to the
      drainage of vein of Labbe and posterior to the deep tentorial insertion of the
      fourth nerve. Finally, special care should be taken to seal the opened mastoid
      cells with muscle and glue, and for the hermetic dura closure using pericranium
      or temporal muscle aponeurosis. Conclusion: The described one burr-hole
      craniotomy may represent the more efficient approach for the management of the
      deep and hardly accessible lesions extended to both middle and posterior fossa.
      Videolink: http://surgicalneurologyint.com/videogallery/presigmoid-approach
      craniotomy-lt.

PMID- 30283714
TI  - Seizure freedom from temporal lobe epilepsy with mesial temporal lobe tumor by
      tumor removal alone without hippocampectomy despite remaining abnormal discharges
      on intraoperative electrocorticography: Report of two pediatric cases and
      reconsideration of the surgical strategy.
AB  - Background: In the surgical treatment of temporal lobe epilepsy with mesial
      temporal lobe tumor, whether to remove the hippocampus aiming for a better
      seizure outcome in addition to removing the tumor is a dilemma. Two pediatric
      cases treated successfully with tumor removal alone are presented. Case
      Description: The first case was an 11-year-old girl with a ganglioglioma in the
      left uncus, and the second case was a 9-year-old girl with a pleomorphic
      xanthoastrocytoma in the left parahippocampal gyrus. In both cases, the
      hippocampus was not invaded, merely compressed by the tumor. Tumor removal was
      performed under intraoperative electrocorticography (ECoG) monitoring. After
      tumor removal, abnormal discharges remained at the hippocampus and adjacent
      temporal cortices, but further surgical interventions were not performed. The
      seizures disappeared completely in both cases. Conclusions: When we must decide
      whether to remove the hippocampus, the side of the lesion, the severity and
      chronicity of the seizures, and the presence of invasion to the hippocampus are
      the factors that should be considered. Abnormal discharges on ECoG at the
      hippocampus or adjacent cortices are one of the factors related to
      epileptogenicity, but it is simply a result of interictal irritation, and it is
      not an absolute indication for additional surgical intervention.

PMID- 30283716
TI  - One burr-hole craniotomy: Posterior interhemispheric approach in Helsinki
      Neurosurgery.
AB  - Background: In this video abstract, we present a one burr-hole craniotomy for the
      posterior interhemispheric approach developed in Helsinki Neurosurgery to access
      posteriorly the medial surface of cerebral hemispheres, falx cerebri, and deep
      midline cerebrovascular structures. Therefore, preoperative imaging is essential
      to achieve an optimal operative corridor for a safest and more effcient approach.
      Case Description: The patient with a papillary tumor of the pineal region is
      placed in sitting position. A midline single-layer skin incision is made in front
      of the superior sagittal sinus. Strong retraction maintains a clean space for
      craniotomy. Aiming to reduce the risk of sinus transgression or cortical veins
      damaging in the eloquent frontal-parietal area, a burr-hole is made over the
      superior sagittal sinus at the anterior border of the bone flap and the bone is
      detached from the dura posteriorly with blunt dissectors. Thus, proximal
      detachment of the dura under some visual control remains safe. A long blunt
      flexible dissector is used during this stage in case of elderly patients with an
      adherent dura. Craniotomy around the superior sagittal sinus is performed to
      expose 2-3 cm of the dura lateral to the sagittal sinus according to the exact
      location of the lesion. Moreover, craniotomy extends slightly over the
      contralateral side to allow some retraction of the sagittal sinus. Two cuts, from
      both sites of the burr-hole, are joined along the posterior midline. A few drill
      holes are made for tack-up sutures. Finally, a hemostatic agent covers the
      sagittal sinus and a sinus-based dura opening is performed under the microscope.
      Conclusion: The described one burr-hole craniotomy may represent a more efficient
      manner for performing a posterior interhemispheric approach. Videolink:
      http://surgicalneurologyint.com/videogallery/posterior-interhemispheric-approach.

PMID- 30283717
TI  - Focused opening of the Sylvian fissure for the management of middle cerebral
      artery aneurysms.
AB  - Background: A wide opening of the Sylvian fissure (SF) regarding the treatment of
      middle cerebral artery (MCA) aneurysm allows us to ensure early proximal control
      by the proximal start of Sylvian dissection and enough comfort for the
      microsurgical manipulation and aneurysm clipping. However, major mechanical
      manipulation of arteries associated with blood oozing into the surgical field may
      increase the incidence of postoperative vasospasm. The risk of Sylvian venous
      injury is bigger, and the damage of the superior temporal gyrus increases the
      risk of postoperative epilepsy as well. A focused opening of the SF based on 18
      years experience of a senior author is an alternative technique we present in
      this video abstract. Technique: A proper preoperative planning and an image-based
      anatomic orientation of the Sylvian opening together with a complete
      understanding of the microanatomy of the clipping field are essential
      requirements for a proper focused SF opening. A patient with an MCA bifurcation
      aneurysm is placed in supine position. The head elevated 20 cm above the cardiac
      level is slightly extended, rotated to the contralateral side, and tilted
      laterally. A lateral supraorbital approach is performed. After cerebrospinal
      fluid release and under high magnification, the opening place of the SF is
      identified. Thus, 10-15 mm opening is made with a sharp needle followed by
      microscissors. Under a keyhole concept, the M1 segment of the MCA is recognized,
      and the aneurysm is carefully dissected. A temporary clipping with a proximal
      control of the M1 segment is followed by a definitive clipping of the aneurysm.
      Postoperative imaging does not show any complication. Conclusion: The focused
      opening of the SF is a less invasive technique for the management of MCA
      bifurcation aneurysms. However, some extra considerations should be taken for
      large or giant aneurysms in which a wide opening of the SF might be required for
      a proper aneurysm manipulation, and for those deep MCA bifurcation aneurysms
      close to the internal carotid artery bifurcation, in which an anterograde
      dissection of the MCA might be more suitable. Videolink:
      http://surgicalneurologyint.com/videogallery/focused-opening-of-the-syvian
      fissure/.

PMID- 30283718
TI  - Anterior clinoidectomy for paraclinoid aneurysms in Helsinki Neurosurgery.
AB  - Background: In this video abstract, we present an intradural anterior
      clinoidectomy for management of some paraclinoid aneurysms. Quick adenosine
      cardiac arrest performed instead of an anterior clinoidectomy and proximal
      temporary clipping usually allows us a proximal control of aneurysms in Helsinki
      Neurosurgery. However, when the neck of the aneurysm remains hidden under the
      anterior clinoid process, or when some complex aneurysms have reduced space for
      placing temporary clips obstructing the definitive clipping, anterior
      clinoidectomy is the most available option. Technique: The patient with multiple
      intracranial aneurysms had a ruptured anterior cerebral artery aneurysm
      associated with a right middle cerebral artery aneurysm and a right small
      paraclinoid aneurysm. The patient underwent surgical clipping of all aneurysms by
      a right lateral supraorbital approach at one-stage surgery. After the associated
      aneurysms were clipped, the hidden paraclinoid aneurysm required an anterior
      clinoidectomy for definitive clipping. A small durotomy over the anterior clinoid
      process was made with microscissors after bipolar coagulation. Subsequently, the
      anterior clinoidectomy was performed under visual control with the use of an
      electric high-speed diamond drill (3 mm diameter). The direction and size of the
      drilling were performed according to the anatomical configuration and exact
      location of the aneurysm determined by the preoperative radiological analysis of
      the case. A definitive clip was applied after complete visualization of aneurysm.
      Postoperative computed tomography angiography demonstrated absence of
      complications. Conclusion: Anterior clinoidectomy is a useful procedure aiming at
      a proper definitive clipping of paraclinoid aneurysms with challenging locations
      and configurations. Videolink: http://surgicalneurologyint.com/videogallery/right
      clinoidectomy/.

PMID- 30283719
TI  - Unedited microneurosurgery of a fourth ventricular ependymoma.
AB  - Background: In this video abstract, we present an unedited microsurgical
      resection of a fourth ventricular ependymoma performed by a senior author (JH).
      Currently, the goal of a standard treatment of a fourth ventricular ependymoma is
      based on microsurgical resection followed by radiochemotherapy. Our aim is to
      demonstrate the efficiency and safety of our microsurgical technique in deep
      brain territories under the principle "simple, clean, and preserving the normal
      anatomy." For this, a midline suboccipital approach and a proper praying sitting
      position are essential. Case Description: The patient is placed in a sitting
      praying position. After a midline suboccipital craniotomy, the ependymoma is
      accessed through telovelar approach. Partial debulking of the tumor follows
      careful separation of cerebellar tonsils; later, cautious dissection along the
      borderline of the tumor is performed. The cranial border of the lesion is
      accessed and the superior limit of the fourth ventricle and aqueduct is reached.
      Vascular feeders of the tumor coming from both posterior inferior cerebellar
      arteries are coagulated and cut. After careful dissection and devascularization
      of the lesion, the ependymoma is pulled out using soft and continuous traction
      with long ring microforceps. The final steps include inspection of remnants into
      the fourth ventricle with an appropriate orientation of the microscope toward the
      aqueduct and both foramina of Luschka. Conclusion: We believe this unedited video
      will provide us all small and big details that a neurosurgeon like a senior
      author JH takes into consideration when performing an efficient and safe surgery
      into the fourth ventricle, under the principle "simple, clean, and preserving the
      normal anatomy surgery." Videolink:
      http://surgicalneurologyint.com/videogallery/4th-ventricle-ependymoma/.

PMID- 30283720
TI  - Prosthetic material degeneration over time as a possible factor in delayed
      recurrence of hemifacial spasm after successful microvascular decompression.
AB  - Background: The effectiveness of microvascular decompression in treating
      hemifacial spasm is widely accepted. However, some experience recurrence of
      hemifacial spasm after successful decompression surgery. Especially, delayed
      recurrence more than 5 years after surgery is rare and the cause of this
      phenomenon is unknown. Case Description: A female underwent microvascular
      decompression to treat her hemifacial spasm 6 years ago. Six years later, her
      hemifacial spasm recurred and she underwent a second surgery. The second surgery
      revealed that the sponge had become fragile, losing the ability to absorb the
      impact of pulsatile compression of the offending artery on the root exit zone of
      her facial nerve. Conclusion: We report a case in which degeneration of material,
      a sponge (polyurethane), used in decompression surgery caused delayed recurrence
      of hemifacial spasm. The selection of appropriate prosthetic materials is
      essential in such functional surgeries.

PMID- 30283721
TI  - Timely Identification of Pregnancy in Noncommunicating Horn of Unicornuate Uterus
      by Three-Dimensional Transvaginal Ultrasonography.
AB  - Pregnancy in the rudimentary horn of a unicornuate uterus is uncommon and needs
      to be diagnosed at early stages to avoid uterine rupture to avert the high
      morbidity and mortality. In this case report, we discussed the advantage of three
      dimensional transvaginal ultrasonography (3D TV-USG) in assessing the early
      pregnancy in the noncommunicating rudimentary horn of uterus. A 23-year-old woman
      approached us for routine pregnancy scan. The location of 5-week pregnancy was
      confirmed in the right noncommunicating horn of a unicornuate uterus by 3D TV
      USG. She has undergone laparohysteroscopy, and excision of a gravid rudimentary
      horn was done. After an interval of 6 months, the patient received fertility
      treatment and conceived consequently. Although magnetic resonance imaging (MRI)
      is an excellent way of diagnosing uterine anomalies, the procedure is expensive,
      time-consuming, and not widely available. 3D USG is less expensive and more
      readily accessible for early diagnosis of uterine anomalies, particularly in
      health-care centers where MRI is not readily available or affordable.

PMID- 30283722
TI  - Monitoring Iron Overload: Relationship between R2* Relaxometry of the Liver and
      Serum Ferritin under Different Therapies.
AB  - Objective: The objective of this study was to evaluate the relationship between
      hepatic magnetic resonance imaging (MRI) with R2* relaxometry and serum ferritin
      in therapy monitoring of patients with iron overload. Further, a possible
      influence of the chosen therapy (phlebotomy or chelation) was assessed. Materials
      and Methods: We retrospectively evaluated 42 patients with baseline and follow-up
      R2* relaxometry and determination of serum ferritin before and during therapeutic
      phlebotomy or iron chelation therapy or watchful waiting, respectively. Linear
      regression analysis was used to analyze the correlation between changes of R2*
      and serum ferritin. Regression lines for different groups were compared with
      analysis of covariance. Results: We found a moderate positive statistical
      correlation (r = 0.509) between serum ferritin and R2*, a moderate positive
      correlation between absolute R2* changes and serum ferritin changes (r = 0.497),
      and a strong correlation for percentage changes (r = 0.712). The correlation
      analysis between relative changes of R2* and serum ferritin for the different
      therapies resulted in a strong correlation between phlebotomy and chelation (r =
      0.855/0.727) and a moderate for no applied therapy (r = 0.536). In 22/92 paired
      examinations, a discordance of R2* and ferritin was found, particularly involving
      patients under chelation. Conclusions: Despite the good correlation between serum
      ferritin and R2* relaxometry in monitoring iron overload, treatment response may
      be misinterpreted when only serum ferritin is considered. Although ferritin is an
      acceptable and far cheaper tool for monitoring, MRI should be performed for
      confirmation, especially in case of unexpected ferritin changes, particularly
      under chelation therapy.

PMID- 30283723
TI  - Caliber-Persistent Labial Artery: A Report of a Rarely Recognized Lip Swelling.
AB  - Calibre-persistent labial artery (CPLA) is a commonly underdiagnosed vascular
      lesion of the lip. CPLA is an arterial branch that penetrates the submucosal
      tissue without loss of calibre. Clinical diagnosis is significant as misdiagnosis
      can lead to profuse haemorrhage following an excisional biopsy or surgical
      excision. Colour Doppler ultrasonography is a safe and non-invasive diagnostic
      tool to confirm the diagnosis. Here, we report a case of a 24-year-old man who
      complained of an asymptomatic pulsating non-progressive nodule on the left side
      of upper lip initially diagnosed as peripheral angiomatous lesion. Diagnosis was
      confirmed by high-resolution Colour Doppler Ultrasonography. The purpose of this
      case report is to highlight the clinical importance and diagnosis of a rarely
      reported soft tissue swelling of the lip to the attention of clinicians.

PMID- 30283725
TI  - REFINING A SUMMER BIOMEDICAL RESEARCH TRAINING PROGRAM FOR AMERICAN INDIAN AND
      ALASKA NATIVE (AIAN) STUDENTS.
AB  - Literature shows that students who enter the science, technology, engineering,
      mathematics, and medical-related (STEMM) pipeline at earlier stages of their
      career are more likely to be successful. This is especially true for
      underrepresented and economically disadvantaged students. Despite the increasing
      number of students entering the pipeline, American Indian and Alaska Native
      (AIAN) students still have a higher attrition rate compared to other ethnic
      groups. Educators and government agencies have worked to improve the success rate
      for AIAN students across all levels and fields by developing various programs
      aimed at training and mentorship. In 2007, the National Institute of Neurological
      Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) in
      Bethesda, MD, increased their outreach efforts for recruiting AIAN students for
      the summer internship program. Our goal was to develop a culturally tailored
      research-training program that could recruit and retain AIAN students into STEMM
      degrees and careers. We adapted an existing program that provides training in
      biomedical science and mentorship at an NINDS research laboratory. From 2007 to
      2016, of the 41 AIAN interns who participated, 35 (85%) remained in STEMM fields.
      Five interns obtained post baccalaureate positions at NIH and four entered
      graduate or medical school. These successful outcomes were brought about only
      after navigating myriad obstacles. We identified obstacles for AIAN student
      participation, and made adaptations to the summer internship. We made design
      decisions regarding recruitment, feasibility, lab placement and mentorship,
      supporting research and social networking, and sustaining AIAN culture. This
      design case highlights the obstacles and strategies for success that we
      developed.

PMID- 30283724
TI  - Diagnosis of sepsis from a drop of blood by measurement of spontaneous neutrophil
      motility in a microfluidic assay.
AB  - Current methods for the diagnosis of sepsis have insufficient precision, causing
      regular misdiagnoses. Microbiological tests can help diagnose sepsis but are
      usually too slow to have an impact on timely clinical-decision making.
      Neutrophils have high sensitivity to infections, yet measurements of neutrophil
      surface markers, genomic changes, and phenotype alterations have had only a
      marginal effect on sepsis diagnosis. Here, we report a microfluidic assay that
      measures the spontaneous motility of neutrophils in the context of plasma, in one
      droplet of blood. We measured the performance of the assay in two independent
      cohorts of critically ill patients suspected of sepsis. In the first cohort, we
      developed a machine-learning-based scoring system (sepsis score) that segregated
      patients with sepsis from those without sepsis. In the second cohort, we
      validated the sepsis score in a double-blinded, prospective case-control study.
      For the 42 patients across the two cohorts, the assay identified sepsis patients
      with 97% sensitivity and 98% specificity. The neutrophil assay could potentially
      be used to accurately diagnose and monitor sepsis in larger populations of at
      risk patients.

PMID- 30283726
TI  - Large Cohort Data Based Group or Community Disease Prevention Design Strategy:
      Strong Heart Study.
AB  - Background and Objective: A multitude of large cohort studies have data on
      incidence rates and predictors of various chronic diseases. However, approaches
      for utilization of these costly collected data and translation of these valuable
      results to inform and guide clinical disease prevention practice are not well
      developed. In this paper we proposed a novel conceptual group/community disease
      prevention design strategy based on large cohort study data. Methods and Results:
      The data from participants (n = 3516; 2056 women) aged 45 to 74 years and the
      diabetes risk prediction model from Strong Heart Study were used. The Strong
      Heart Study is a population-based cohort study of cardiovascular disease and its
      risk factors in American Indians. A conceptual group/community disease prevention
      design strategy based on large cohort data was initiated. The application of the
      proposed strategy for group diabetes prevention was illustrated. Discussion: The
      strategy may provide reasonable solutions to the prevention design issues. These
      issues include complex associations of a disease with its combined and correlated
      risk factors, individual differences, choosing intervention risk factors and
      setting their appropriate, attainable, gradual and adaptive goal levels for
      different subgroups, and assessing effectiveness of the prevention program.
      Conclusions: The strategy and methods shown in the illustration example can be
      analogously adopted and applied for other diseases preventions. The proposed
      strategy for a target group/community in a population provides a way to translate
      and apply epidemiological study results to clinical disease prevention practice.

PMID- 30283727
TI  - Aspects of Data Ethics in a Changing World: Where Are We Now?
AB  - Ready data availability, cheap storage capacity, and powerful tools for
      extracting information from data have the potential to significantly enhance the
      human condition. However, as with all advanced technologies, this comes with the
      potential for misuse. Ethical oversight and constraints are needed to ensure that
      an appropriate balance is reached. Ethical issues involving data may be more
      challenging than the ethical challenges of some other advanced technologies
      partly because data and data science are ubiquitous, having the potential to
      impact all aspects of life, and partly because of their intrinsic complexity. We
      explore the nature of data, personal data, data ownership, consent and purpose of
      use, trustworthiness of data as well as of algorithms and of those using the
      data, and matters of privacy and confidentiality. A checklist is given of topics
      that need to be considered.

PMID- 30283728
TI  - Data-Driven Investment Strategies for Peer-to-Peer Lending: A Case Study for
      Teaching Data Science.
AB  - We develop a number of data-driven investment strategies that demonstrate how
      machine learning and data analytics can be used to guide investments in peer-to
      peer loans. We detail the process starting with the acquisition of (real) data
      from a peer-to-peer lending platform all the way to the development and
      evaluation of investment strategies based on a variety of approaches. We focus
      heavily on how to apply and evaluate the data science methods, and resulting
      strategies, in a real-world business setting. The material presented in this
      article can be used by instructors who teach data science courses, at the
      undergraduate or graduate levels. Importantly, we go beyond just evaluating
      predictive performance of models, to assess how well the strategies would
      actually perform, using real, publicly available data. Our treatment is
      comprehensive and ranges from qualitative to technical, but is also modular-which
      gives instructors the flexibility to focus on specific parts of the case,
      depending on the topics they want to cover. The learning concepts include the
      following: data cleaning and ingestion, classification/probability estimation
      modeling, regression modeling, analytical engineering, calibration curves, data
      leakage, evaluation of model performance, basic portfolio optimization,
      evaluation of investment strategies, and using Python for data science.

PMID- 30283729
TI  - Electronic Health Record-Based Screening for Substance Abuse.
AB  - Existing methods of screening for substance abuse (standardized questionnaires or
      clinician's simply asking) have proven difficult to initiate and maintain in
      primary care settings. This article reports on how predictive modeling can be
      used to screen for substance abuse using extant data in electronic health records
      (EHRs). We relied on data available through Veterans Affairs Informatics and
      Computing Infrastructure (VINCI) for the years 2006 through 2016. We focused on
      4,681,809 veterans who had at least two primary care visits; 829,827 of whom had
      a hospitalization. Data included 699 million outpatient and 17 million inpatient
      records. The dependent variable was substance abuse as identified from 89
      diagnostic codes using the Agency for Healthcare Quality and Research
      classification of diseases. In addition, we included the diagnostic codes used
      for identification of prescription abuse. The independent variables were 10,292
      inpatient and 13,512 outpatient diagnoses, plus 71 dummy variables measuring age
      at different years between 20 and 90 years. A modified naive Bayes model was used
      to aggregate the risk across predictors. The accuracy of the predictions was
      examined using area under the receiver operating characteristic (AROC) curve in
      20% of data, randomly set aside for the evaluation. Many physical/mental
      illnesses were associated with substance abuse. These associations supported
      findings reported in the literature regarding the impact of substance abuse on
      various diseases and vice versa. In randomly set-aside validation data, the model
      accurately predicted substance abuse for inpatient (AROC = 0.884), outpatient
      (AROC = 0.825), and combined inpatient and outpatient (AROC = 0.840) data. If one
      excludes information available after substance abuse is known, the cross
      validated AROC remained high, 0.822 for inpatient and 0.817 for outpatient data.
      Data within EHRs can be used to detect existing or predict potential future
      substance abuse.

PMID- 30283730
TI  - Efficacy of Intravenous Acetaminophen in Length of Stay and Postoperative Pain
      Control in Laparoscopic Roux-en-Y Gastric Bypass Surgery Patients.
AB  - Background: Opiate-based pain medications may incur adverse effects following
      bariatric surgery. The aim of this study was to evaluate the efficacy of
      intravenous Acetaminophen (IVAPAP) on length of stay (LOS) after laparoscopic
      Roux-en-Y gastric bypass (LRYGB) surgery. Methods: This was a prospective, double
      blind, randomized controlled trial conducted from October 2011 to March 2014 at a
      416-bed teaching hospital. Eighty-nine total patients were included (control
      group, n = 45; treatment group, n = 44). Patients were administered either 1000
      mg of IVAPAP or placebo every 6 h beginning preoperatively and continuing for
      four doses. LOS, total narcotic consumption, pain and nausea scores, time to
      return of flatus (ROF), and postoperative rescue pain medication used were
      measured during the first 24 h after surgery. Results: LOS was significantly
      decreased in the treatment group compared with control (2.72 days vs. 3.18 days;
      p = 0.03). There was significant reduction in time to ROF (1.87 days vs. 2.24
      days; p = 0.04). Pain was significantly decreased in the first 2 postoperative
      hours in the treatment group (p = 0.02). Total opioid consumption, postoperative
      nausea scores, and use of rescue pain medications were not affected. Conclusions:
      The use of IVAPAP significantly decreases LOS following LRYGB, improves acute
      postoperative pain control, and mediates quicker return of bowel function.

PMID- 30283731
TI  - Lessons learned from rindopepimut treatment in patients with EGFRvIII-expressing
      glioblastoma.

PMID- 30283732
TI  - KRAS RENAISSANCE(S) in Tumor Infiltrating B Cells in Pancreatic Cancer.
AB  - KRAS is a driver mutation for malignant transformation. It is found in 30% of all
      cancers and in 90% of pancreatic cancers. The identification of small molecules
      selectively inhibiting KRAS mutants has been challenging, yet mutant KRAS has
      recently been shown to be targeted by tumor-infiltrating lymphocyte (TIL)-derived
      T cells that confer tumor regression upon adoptive transfer. Furthermore, a human
      IgG1 monoclonal antibody interfering with mutant KRAS function inside the cell
      has been described to inhibit growth of KRAS-mutant xenografts in tumor-bearing
      mice. B cells have been described to infiltrate pancreatic cancer and may be
      associated with tertiary lymphoid structures associated with good prognosis, or,
      in contrast, promote tumor growth. However, their function, nor their antigen
      specificity has been clearly defined. We discuss here the presence of tumor
      infiltrating B cells (TIB) in patients with pancreatic cancer that produce KRAS
      mutant specific IgG, underlining that intratumoral T and B cells may exclusively
      target mutant KRAS. KRAS-specific IgG may, therefore, serve as a readout of the
      activation of both arms of the anti-tumor adaptive immune armament although some
      B-cell populations may promote tumor progression.

PMID- 30283734
TI  - Reflections on the Management of Graves' Hyperthyroidism.

PMID- 30283733
TI  - Tumor-Intrinsic PD-L1 Signaling in Cancer Initiation, Development and Treatment:
      Beyond Immune Evasion.
AB  - Although the role of PD-L1 in suppressing the anti-tumor immune response is
      extensively documented, recent discoveries indicate a distinct tumor-intrinsic
      role for PD-L1 in modulating epithelial-to-mesenchymal transition (EMT), cancer
      stem cell (CSC)-like phenotype, metastasis and resistance to therapy. In this
      review, we will focus on the newly discovered functions of PD-L1 in the
      regulation of cancer development, describe underlying molecular mechanisms
      responsible for PD-L1 upregulation and discuss current insights into novel
      components of PD-L1 signaling. Furthermore, we summarize our current
      understanding of the link between PD-L1 signaling and the EMT program as well as
      the CSC state. Tumor cell-intrinsic PD-L1 clearly contributes to cancer stemness,
      EMT, tumor invasion and chemoresistance in multiple tumor types. Conversely,
      activation of OCT4 signaling and upregulation of EMT inducer ZEB1 induce PD-L1
      expression in cancer cells, thereby suggesting a possible immune evasion
      mechanism employed by cancer stem cells during metastasis. Our meta-analysis
      demonstrated that PD-L1 is co-amplified along with MYC, SOX2, N-cadherin and
      SNAI1 in the TCGA endometrial and ovarian cancer datasets. Further identification
      of immune-independent PD-L1 functions and characterization of crucial signaling
      events upstream or downstream of PD-L1 in diverse cancer types and specific
      cancer subtypes, would provide additional targets and new therapeutic approaches.

PMID- 30283736
TI  - Thyroid Hemiagenesis in a Thyroiditis Prone Mouse Strain.
AB  - Background: Thyroid hemiagenesis, a rare congenital condition detected by
      ultrasound screening of the neck, is usually not manifested clinically in humans.
      This condition has been reported in mice with hypothyroidism associated with
      induced deficiency in paired box 8 and NK2 homeobox 1, sonic hedgehog, or T-box
      1. Unexpectedly, we observed thyroid hemiagenesis in NOD.H2h4 mice, an unusual
      strain that spontaneously develops iodide enhanced thyroid autoimmunity but
      remains euthyroid. Objectives and Methods: First, to compare mice with thyroid
      hemiagenesis versus bilobed littermates for serum T4, autoantibodies to
      thyroglobulin (ELISA) and thyroid peroxidase (TPO; flow cytometry with eukaryotic
      cells expressing mouse TPO), gross anatomy, and thyroid histology; second, to
      estimate the percentage of mice with thyroid hemiagenesis in the NOD.H2h4 mice we
      have studied over 6 years. Results: Thyroid hemiagenesis was observed in 3 of
      1,025 NOD.H2h4 mice (2 females, 1 male; 0.3$). Two instances of hemiagenesis were
      in wild-type females and one in a transgenic male expressing the human TSHR A
      subunit in the thyroid. Two mice had very large unilobed glands, as in some human
      cases with this condition. Thyroid lymphocytic infiltration, serum T4, and the
      levels of thyroid autoantibodies were similar in mice with thyroid hemiagenesis
      and bilobed littermates. Conclusions: Unlike hypothyroidism associated with
      hemiagenesis in transcription factor knockout mice, hemiagenesis in euthyroid
      NOD.H2h4 mice occurs spontaneously and is phenotypically similar to that
      occasionally observed in humans.

PMID- 30283738
TI  - The Krakow Declaration on Iodine: Tasks and Responsibilities for Prevention
      Programs Targeting Iodine Deficiency Disorders.
AB  - On April 18, 2018 the EUthyroid consortium released the Krakow Declaration on
      Iodine in response to the increasing concern about the deteriorating commitment
      of policymakers to address public health strategies against iodine deficiency
      disorders (IDD) in the European populations. Regulators and policymakers should
      harmonize obligatory Universal Salt Iodization to ensure free trade of fortified
      foodstuffs in Europe. Similarly, iodized animal feed requires regulatory approval
      to ensure free trade within the EU. National governments and public health
      authorities have to perform harmonized monitoring and evaluation of fortification
      programs at regular intervals to ensure optimal iodine supply to the population.
      Scientists, together with public health care workers, patient organizations,
      industry, and the public should support measures necessary to ensure that IDD
      prevention programs are sustainable, as appropriate within a rapidly changing
      environment and further social awareness of the issue. The declaration defines
      measures and responsibilities to optimize IDD prevention.

PMID- 30283737
TI  - How Do We Improve the Impact of Iodine Deficiency Disorders Prevention in Europe
      and Beyond?
AB  - Background: Iodine deficiency disorders (IDD) represent a global health threat to
      individuals and societies. IDD prevention programmes have been introduced in many
      parts of the world. However, challenges remain, particularly in Europe due to
      fragmentation and diversity of approaches that are not harmonized. Objectives:
      This review is dedicated to the public-health impact of IDD prevention
      programmes. It sums up experiences collected by the EUthyroid consortium so far
      and provides information on stakeholders that should be involved in actions
      directed to improve the impact of IDD prevention. Methods: A joint European
      database for combining registry-based outcome and monitoring data as well as
      tools for harmonizing study methods were established. Methods for analyzing
      thyroglobulin from a dried blood spot are available for assessing the iodine
      status in the general population and at-risk groups. Mother-child cohorts are
      used for in-depth analysis of the potential impact of mild-to-moderate iodine
      deficiency on the neurocognitive development of the offspring. A decision
      analytic model has been developed to evaluate the long-term effectiveness and
      cost effectiveness of IDD prevention programmes. Results: EUthyroid has produced
      tools and infrastructure to improve the quality of IDD monitoring and follows a
      dissemination strategy targeting policymakers and the general public. There are
      tight connections to major stakeholders in the field of IDD monitoring and
      prevention. Conclusions: EUthyroid has taken steps towards achieving a euthyroid
      Europe. Our challenge is to inspire a greater sense of urgency in both
      policymakers and the wider public to address this remediable deficit caused by
      IDD.

PMID- 30283735
TI  - 2018 European Thyroid Association Guideline for the Management of Graves'
      Hyperthyroidism.
AB  - Graves' disease (GD) is a systemic autoimmune disorder characterized by the
      infiltration of thyroid antigen-specific T cells into thyroid-stimulating hormone
      receptor (TSH-R)-expressing tissues. Stimulatory autoantibodies (Ab) in GD
      activate the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone
      production and secretion. Diagnosis of GD is straightforward in a patient with
      biochemically confirmed thyrotoxicosis, positive TSH-R-Ab, a hypervascular and
      hypoechoic thyroid gland (ultrasound), and associated orbitopathy. In GD,
      measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential
      diagnosis, prior to stopping antithyroid drug (ATD) treatment and during
      pregnancy. Graves' hyperthyroidism is treated by decreasing thyroid hormone
      synthesis with the use of ATD, or by reducing the amount of thyroid tissue with
      radioactive iodine (RAI) treatment or total thyroidectomy. Patients with newly
      diagnosed Graves' hyperthyroidism are usually medically treated for 12-18 months
      with methimazole (MMI) as the preferred drug. In children with GD, a 24- to 36
      month course of MMI is recommended. Patients with persistently high TSH-R-Ab at
      12-18 months can continue MMI treatment, repeating the TSH-R-Ab measurement after
      an additional 12 months, or opt for therapy with RAI or thyroidectomy. Women
      treated with MMI should be switched to propylthiouracil when planning pregnancy
      and during the first trimester of pregnancy. If a patient relapses after
      completing a course of ATD, definitive treatment is recommended; however,
      continued long-term low-dose MMI can be considered. Thyroidectomy should be
      performed by an experienced high-volume thyroid surgeon. RAI is contraindicated
      in Graves' patients with active/severe orbitopathy, and steroid prophylaxis is
      warranted in Graves' patients with mild/active orbitopathy receiving RAI.

PMID- 30283739
TI  - Can Suspicious Ultrasound Features Predict BRAFV600E Status in Papillary Thyroid
      Cancer?
AB  - Background: Papillary thyroid carcinoma (PTC) can be predicted from certain
      suspicious ultrasound (US) features of thyroid nodules. The aim of this study was
      to examine if these suspicious features can predict the more aggressive PTC
      associated with B-type Raf kinase (BRAFV600E) mutation. Methods: This was a
      retrospective review of prospectively collected data on patients with PTC and
      known BRAFV600E status. All patients underwent preoperative US by the same
      surgeon who performed all the operations. We divided patients into BRAFV600E
      positive and negative groups. All ultrasonographic data were collected including
      nodule size, echogenicity, solid or cystic nature, presence of calcifications,
      irregular margins, and internal vascularity. Results: Of 141 patients with PTC,
      BRAFV600E mutation was detected in 48 (34.0$) patients. There was no significant
      difference in nodule size (2.06 cm +/- 1.37 vs. 2.15 cm +/-1.55, p = 0.75)
      between BRAFV600E positive and negative groups. BRAFV600E positivity was
      associated with higher rates of -hypoechogenicity (57.5$ vs. 36.6, p = 0.02),
      calcifications (48.9 vs. 19.4$, p < 0.01), and irregular margins (21.3 vs. 6.5$,
      p < 0.01). There was no significant difference in the noncystic nature or
      internal vascularity between BRAFV600E positive and negative groups. The presence
      of all suspicious US features is associated with a positive predictive value of
      100.0$. In the absence of all suspicious features, the negative predictive value
      was 84.2$. When suspicious lymph nodes (LNs) detected by preoperative US were
      compared, there was no significant difference between BRAFV600E positive and
      negative groups (30.6 vs. 21.7$, p = 0.35). Conclusion: The presence of multiple
      suspicious US findings of thyroid nodules can predict the BRAFV600E mutation
      status of papillary thyroid cancer nodules. The highest accuracy overall (93.2$)
      was achieved by combining calcification, irregular margins, and hypoechogenicity
      with extrathyroidal extension and LN metastasis. Future multi-institutional
      studies are warranted to help surgeons with risk stratification and operative
      planning for patients with papillary thyroid cancer.

PMID- 30283740
TI  - Prognostic Value of Stimulated Thyroglobulin Levels at the Time of Radioiodine
      Administration in Differentiated Thyroid Cancer.
AB  - Objective: The prognostic value of stimulated thyroglobulin (sTg) and Tg-related
      parameters prior to and immediately after radioactive iodine (RAI) administration
      was assessed in a cohort of patients presenting with differentiated thyroid
      cancer (DTC) as a predictor of recurrent or progressive structural disease.
      Methods: Clinical records of 180 DTC patients were retrospectively reviewed, and
      serum TSH, Tg, and Tg antibodies were recorded just before RAI administration
      (pre-) and at the time of whole body scanning (post-). Based on the results of
      initial staging and RAI scintigraphy, patients were divided into two groups:
      those who were considered to be structurally disease-free after thyroidectomy and
      RAI (group 1) and those who were not (group 2). Univariate analyses were
      performed for pre-Tg, ratioTg (post-Tg/pre-Tg), and other clinical and
      pathological markers for long-term outcome, as well as separate bivariate
      analyses focusing on pre-Tg to correct for possible confounders. Different pre-Tg
      cut-off values for predicting structural disease recurrence were assessed in a
      subgroup of patients in group 1 prepared with thyroid hormone withdrawal.
      Results: In group 1, (n = 166) male gender, higher T-stage and both Tg-related
      parameters proved to be significant risk factors for structural disease relapse.
      Of all candidate variables, only higher T-stage served to predict progressive
      structural disease in group 2 (n = 14). Subgroup analysis showed a negative
      predictive value of 91.67$ for pre-Tg < 10 ug/L. Conclusion: The sTg value at the
      time of RAI administration may be helpful in predicting structural disease
      recurrence in patients with DTC.

PMID- 30283741
TI  - Low-Dose Radioiodine Ablation in Patients with Low-Risk Differentiated Thyroid
      Cancer.
AB  - Aim: Based on the response criteria of the 2015 American Thyroid Associations
      guidelines, our objectives were to -determine the response rate when using a low
      dose of -131-I GBq in patients with low-risk differentiated thyroid cancer
      (LRDTC) and the influence of clinical and analytical variables on the prediction
      of complete response. Methods: We performed a multicentre and longitudinal study,
      including patients who were operated for LRDTC and who underwent radioiodine
      remnant ablation with a low-dose of 131-I. All patients were assessed at 6-12
      months, and their status was classified as complete (excellent response) or
      incomplete response (structural incomplete, biochemical incomplete or
      indeterminate response). Various factors including age, gender, histology, tumour
      focality and size, stage, time from surgery to treatment, type of thyroid
      stimulating hormone (TSH) stimulation, preablation serum thyroglobulin (pTg),
      antiTg antibodies (pAntiTgAb) and TSH (pTSH) levels were also analysed in order
      to predict the complete response rate. Results: Of 108 patients, 79.6$ achieved
      complete response and the remaining showed incomplete response (2.9, 5.5 and 12$
      due to biochemical incomplete, structural incomplete and indeterminate response
      respectively). Six patients received a new dose of 131-I. Tumour size and
      pAntiTgAb were the only factors related to therapeutic response (p = 0.03 and p <
      0.01, respectively). However, pAntiTgAb was the only independent factor related
      to complete -response. Patients with complete response showed lower pTg than
      those with incomplete response (5.1 +/- 12.9 vs. 11.2 +/- 25 ng/mL) although
      without statistical significance (p = 0.14). There was no significant difference
      in the response rate depending on the thyrotropin stimulation methods.
      Conclusions: A low dose of 131-I was sufficient for reaching a complete response
      at 6-12 months of follow-up in the majority of patients with LRDTC. Tumour size
      and pAntiTgAb variables were related to therapeutic response.

PMID- 30283743
TI  - Reverse Epidemiology: An Experimental Framework to Drive Leishmania Biomarker
      Discovery in situ by Functional Genetic Screening Using Relevant Animal Models.
AB  - Leishmania biomarker discovery remains an important challenge that needs to be
      revisited in light of our increasing knowledge on parasite-specific biology,
      notably its genome instability. In the absence of classical transcriptional
      regulation in these early-branching eukaryotes, fluctuations in transcript
      abundance can be generated by gene and chromosome amplifications, which have been
      linked to parasite phenotypic variability with respect to virulence, tissue
      tropism, and drug resistance. Conducting in vitro evolutionary experiments to
      study mechanisms of Leishmania environmental adaptation, we recently validated
      the link between parasite genetic amplification and fitness gain, thus defining
      gene and chromosome copy number variations (CNVs) as important Leishmania
      biomarkers. These experiments also demonstrated that long-term Leishmania culture
      adaptation can strongly interfere with epidemiologically relevant, genetic
      signals, which challenges current protocols for biomarker discovery, all of which
      rely on in vitro expansion of clinical isolates. Here we propose an experimental
      framework independent of long-term culture termed "reverse" epidemiology, which
      applies established protocols for functional genetic screening of cosmid
      transfected parasites in animal models for the identification of clinically
      relevant genetic loci that then inform targeted field studies for their
      validation as Leishmania biomarkers.

PMID- 30283742
TI  - Non-vesicular Lipid Transport Machinery in Entamoeba histolytica.
AB  - Eukaryotic cells are organized into separate membrane-bound compartments that
      have specialized biochemical signature and function. Maintenance and regulation
      of distinct identity of each compartment is governed by the uneven distribution
      and intra-cellular movement of two essential biomolecules, lipids, and proteins.
      Non-vesicular lipid transport mediated by lipid transfer proteins plays a pivotal
      role in intra-cellular lipid trafficking and homeostasis whereas vesicular
      transport plays a central role in protein trafficking. Comparative study of lipid
      transport machinery in protist helps to better understand the pathogenesis and
      parasitism, and provides insight into eukaryotic evolution. Amebiasis, which is
      caused by Entamoeba histolytica, is one of the major enteric infections in
      humans, resulting in 40-100 thousand deaths annually. This protist has undergone
      remarkable alterations in the content and function of its sub-cellular
      compartments as well represented by its unique diversification of mitochondrion
      related organelle, mitosome. We conducted domain-based search on AmoebaDB coupled
      with bioinformatics analyses and identified 22 potential lipid transfer protein
      homologs in E. histolytica, which are grouped into several sub-classes. Such in
      silico analyses have demonstrated the existence of well-organized lipid transport
      machinery in this parasite. We summarized and discussed the conservation and
      unique features of the whole repertoire of lipid transport proteins in E.
      histolytica.

PMID- 30283746
TI  - Editorial: Biology and Pathogenesis of Legionella.

PMID- 30283745
TI  - Mycobacterium tuberculosis Virulent Factor ESAT-6 Drives Macrophage
      Differentiation Toward the Pro-inflammatory M1 Phenotype and Subsequently
      Switches It to the Anti-inflammatory M2 Phenotype.
AB  - Tuberculosis, a human infectious disease caused by Mycobacterium tuberculosis
      (M.tb), is still a major cause of morbidity and mortality worldwide. The success
      of M.tb as a pathogen relies mainly on its ability to divert the host innate
      immune responses. One way by which M.tb maintains a persistent infection in a
      "silent" granuloma is to inhibit inflammation and induce an immunoregulatory
      phenotype in host macrophages (MPhis). However, M.tb effectors governing the
      switch of MPhis from the pro-inflammatory M1 to the anti-inflammatory M2
      phenotype remain to be determined. The Early Secreted Antigenic Target 6 kDa or
      ESAT-6, has been implicated in the virulence and pathogenesis of tuberculosis.
      Here, we investigated roles of ESAT-6 in MPhi differentiation and polarization.
      We found that treatment of human monocytes with ESAT-6 did not interfere with
      differentiation of M1 MPhis. However, ESAT-6 promoted differentiation of M0 and
      M2 MPhis toward the M1 phenotype, as indicated by secretion of pro-inflammatory
      cytokines IL-6, IL-12, and TNF-alpha, and induction of a typical M1
      transcriptional signature. Interestingly, we found that ESAT-6 switched terminal
      full activation of M1 polarized MPhis to the M2 phenotype. Indeed, in the pro
      inflammatory M1 MPhis, ESAT-6 was able to inhibit IL-12 and TNF-alpha secretion
      and stimulate that of IL-10. Moreover, gene expression profiling of these cells
      showed that ESAT-6 induced downregulation of M1 MPhi cell surface molecules CD80
      and CD86, transcription factors IRF5 and c-MAF, cytokines IL-12, IL-10, and IL-6,
      as well as chemokines CXCL10 and CXCL1. Overall, our findings suggest ESAT-6 as
      being one of the effectors used by M.tb to induce the pro-inflammatory M1
      phenotype at the primo-infection; a prerequisite step to promote granuloma
      formation and subsequently drive the phenotype switch of MPhi polarization from
      M1 to M2 at a later stage of the infection. Our study improves current knowledge
      regarding mechanisms of virulence of M.tb and may be helpful to develop novel
      tools targeting ESAT-6 for a better and more efficient treatment of tuberculosis.

PMID- 30283744
TI  - In Search of Biomarkers for Pathogenesis and Control of Leishmaniasis by Global
      Analyses of Leishmania-Infected Macrophages.
AB  - Leishmaniasis is a vector-borne, neglected tropical disease with a worldwide
      distribution that can present in a variety of clinical forms, depending on the
      parasite species and host genetic background. The pathogenesis of this disease
      remains far from being elucidated because the involvement of a complex immune
      response orchestrated by host cells significantly affects the clinical outcome.
      Among these cells, macrophages are the main host cells, produce cytokines and
      chemokines, thereby triggering events that contribute to the mediation of the
      host immune response and, subsequently, to the establishment of infection or,
      alternatively, disease control. There has been relatively limited commercial
      interest in developing new pharmaceutical compounds to treat leishmaniasis.
      Moreover, advances in the understanding of the underlying biology of Leishmania
      spp. have not translated into the development of effective new chemotherapeutic
      compounds. As a result, biomarkers as surrogate disease endpoints present several
      potential advantages to be used in the identification of targets capable of
      facilitating therapeutic interventions considered to ameliorate disease outcome.
      More recently, large-scale genomic and proteomic analyses have allowed the
      identification and characterization of the pathways involved in the infection
      process in both parasites and the host, and these analyses have been shown to be
      more effective than studying individual molecules to elucidate disease
      pathogenesis. RNA-seq and proteomics are large-scale approaches that characterize
      genes or proteins in a given cell line, tissue, or organism to provide a global
      and more integrated view of the myriad biological processes that occur within a
      cell than focusing on an individual gene or protein. Bioinformatics provides us
      with the means to computationally analyze and integrate the large volumes of data
      generated by high-throughput sequencing approaches. The integration of genomic
      expression and proteomic data offers a rich multi-dimensional analysis, despite
      the inherent technical and statistical challenges. We propose that these types of
      global analyses facilitate the identification, among a large number of genes and
      proteins, those that hold potential as biomarkers. The present review focuses on
      large-scale studies that have identified and evaluated relevant biomarkers in
      macrophages in response to Leishmania infection.

PMID- 30283747
TI  - Comparative Viral Sampling in the Sinonasal Passages; Different Viruses at
      Different Sites.
AB  - Background: With the emergence of the microbiome as an important factor in health
      and disease in the respiratory tract standardised, validated techniques are
      required for its accurate characterisation. No standardised technique has been
      reported specifically for viral sampling in the sinonasal passages. Aim: To
      optimise viral sampling techniques from the sinonasal cavity. Methods: Sterile
      cytology brushes were used under endoscopic guidance to sample the sinonasal
      mucosa at time of endoscopic sinus surgery at both the middle and inferior
      meatuses (MM and IM). DNA and RNA were extracted from the samples and underwent
      PCR or RT-PCR testing, respectively, for a panel of 15 common upper respiratory
      tract viruses. Results: Twenty-four adult patients were recruited for this study.
      18/24 (75%) patients were positive for virus in at least one site, while 8/24
      (33%) were positive for virus at both sites. The mean number of viruses
      identified at the two sites were similar (0.875 +/- 0.899 at the MM vs. 0.750 +/-
      1.032 at the IM). 6/24 (25%) of patients showed no virus at either site, while
      3/24 (12.5%) demonstrated the same viral species at both sites. Conclusion:
      Although the number of viruses present at different sites with the nasal cavity
      are similar, discord exists in the viral species between sites. It is therefore
      recommended that both sites are sampled in the clinical and research setting
      better to characterise the viral species within the nasal cavity.

PMID- 30283748
TI  - Correlation between B-Type Natriuretic Peptide and N-Terminal pro-B-Type
      Natriuretic Peptide in a Large Japanese Population at Risk of Stage A Heart
      Failure.
AB  - Background: The measurements of B-type natriuretic peptide (BNP) and N-terminal
      pro-B-type natriuretic peptide (NT-proBNP) are useful for ruling out heart
      failure and as prognostic markers in not only heart failure populations but also
      general populations. It is not clear whether these two biomarkers are elevated in
      parallel or associated with demographic characteristics in large populations at
      risk of stage A heart failure. Here we investigated the relationship between BNP
      and NT-proBNP and extended the evaluation of this association to known
      demographic disparities in stage A heart failure. Methods: Of 4,310 ambulatory
      patients, we analyzed the cases of the 3,643 (mean age 65 +/- 11 years, 46$ male,
      and 79$ on antihypertensive medication) patients whose serum BNP and NT-proBNP
      levels were both measured and who had a history of and/or risk factors for
      cardiovascular disease from the Japan Morning Surge-Home Blood Pressure (J-HOP)
      Study dataset. Results: The median (25th-75th percentiles) BNP and NT-proBNP
      values were 18.7 (9.3-38.5) pg/mL and 50.3 (25.5-97.4) pg/mL. There was a
      significant association between log-transformed BNP and log-transformed NT-proBNP
      (r = 818, p < 0.001). A multiple linear regression analysis showed that log
      transformed NT-proBNP was significantly associated with log-transformed BNP (beta
      coefficient = 0.774, p < 0.001). When stratified by demographic characteristics,
      these associations remained (all p < 0.001). Conclusion: In a large Japanese
      population at risk of stage A heart failure, there was a significant association
      between BNP and NT-proBNP after adjustment and stratification by demographics.

PMID- 30283749
TI  - Evaluation of the Accuracy of a New Cuffless Magnetoplethysmography Blood
      Pressure Monitor in Hypertensive Patients.
AB  - Objective: There is a growing demand for cuffless blood pressure (BP) measurement
      as an easy alternative to cuff-occlusion-based BP measurement. We assessed the
      accuracy of a new cuffless, watch-style BP monitor with a magnetoplethysmography
      (MPG) sensor compared to two standard auscultatory and oscillatory BP monitors.
      Subjects and Methods: A total of 34 patients with uncontrolled hypertension
      (systolic BP >=150 mm Hg or diastolic BP >=95 mm Hg) were enrolled in the study.
      BP was measured by two conventional monitors and the new device during the pre
      exercise phase, during isometric handgrip exercise, and during the recovery phase
      (5 min after exercise). The correlation between monitors was assessed using
      intraclass correlation coefficient (ICC) and Bland-Altman plots. Results:
      Although two reference monitors produced highly correlated BP measurements, each
      was differentially correlated with BP measurements obtained by the new MPG
      monitor. During exercise, the mean difference between systolic BP obtained by the
      MPG and oscillatory monitors was >7 mm Hg with an ICC of 0.549 (95$ CI 0.264
      0.746) in systole and 0.737 (95$ CI 0.534-0.859) in diastole. The ICC between the
      auscultatory monitor and the MPG monitor was 0.753 (95$ CI 0.559-0.868) in
      systole and 0.841 (95$ CI 0.706-0.918) in diastole after exercise. Bland-Altman
      plots also indicated that the performance of the new MPG device was very similar
      to that of the auscultatory monitor. Conclusion: Although the performance of the
      new MPG monitor was comparable to that of the reference monitors used in this
      study, improved stability and accuracy are necessary for accurate BP evaluation
      during dynamic activity.

PMID- 30283750
TI  - High-Intensity Statin Therapy Is "Too Much," Thus Not Indicated for Very Elderly
      Patients.
AB  - Purpose: Although moderate- to high-intensity statin therapy is increasingly
      recommended in cardiovascular disease patients, the efficacy and safety in
      elderly patients have not been proven clearly. Here, we compare the effect of
      various-intensity statins between elderly and very elderly patients. Methods:
      43,870 patients over 65 years old who were treated with statins were screened
      using electronic medical record data. Results: We evaluated 451 patients in the
      elderly group aged 65-74 years and 159 patients in the very elderly group over 75
      years old. Baseline cholesterol profiles were similar between the 2 groups, but
      the 10-year atherosclerotic cardiovascular disease (ASCVD) risk was significantly
      higher in the very elderly (20.9 +/- 11.5$ vs. 37.2 +/- 13.6$, p < 0.001). The
      reduction rate of low-density lipoprotein (LDL) (-40.2 +/- 21.3$ vs. -39.3 +/-
      21.0$, p = 0.634) and the ratio of target LDL attainment (74.2 vs. 79.2$, p =
      0.252) were similar between the 2 groups. Low-intensity statins showed comparable
      LDL cholesterol reduction with moderate-intensity statins both in the elderly and
      the very elderly groups. The 10-year ASCVD risk reduction was similar between the
      2 groups (-3.5 +/- 4.9$ vs. -3.0 +/- 8.4$, p = 0.480), but in the very elderly
      group, no different ASCVD reduction rate was shown in low- to high-intensity
      statins (p = 0.784). Only the elderly group showed a significant correlation (r =
      0.112, p = 0.017) with LDL reduction and 10-year ASCVD risk. Interestingly, the
      incidence of adverse drug reaction (ADR) was higher in the very elderly group
      (4.4$) than in the elderly group (2.7$) and was more frequent in high-intensity
      statin therapy. Conclusion: The efficacy of statins in LDL reduction was similar
      between the elderly and very elderly population. However, the benefit of moderate
      to high-intensity statins is limited considering potential ADR. Therefore, the
      stepwise intensification of statin therapy might be necessary for the very
      elderly in spite of the higher cardiovascular risk.

PMID- 30283751
TI  - Evaluation of Central Blood Pressure in an Asian Population: Comparison between
      Brachial Oscillometry and Radial Tonometry Methods.
AB  - Background: New devices have recently been developed using various features of
      the waveform derived from a brachial cuff for noninvasive estimation of central
      systolic blood pressure (SBP). Central SBP estimated from brachial oscillometry
      has never been compared with that estimated from radial tonometry in a Japanese
      population. Subjects and Methods: We recruited 155 Japanese volunteers (mean age
      58 +/- 16 years, range 18-99 years; 66.5$ women) and estimated their central SBP
      using brachial oscillometry (Mobil-O-Graph) or radial tonometry (SphygmoCor).
      Results: The mean (standard deviation) peripheral SBP and central SBP measured
      with brachial oscillometry was 128 +/- 18 mm Hg and 118 +/- 16 mm Hg,
      respectively, while the central SBP estimated using radial tonometry was 119 +/-
      18 mm Hg. The mean (standard deviation) difference in estimated central SBP
      between brachial oscillometry and radial tonometry was 0.36 +/- 5.9 mm Hg, and
      the central SBPs estimated using these devices were strongly correlated (r =
      0.946, intraclass correlation coefficient = 0.940, p < 0.001). Conclusion:
      Central SBP estimated using brachial oscillometry was similar to that estimated
      from radial tonometry in a Japanese population.

PMID- 30283752
TI  - Obstructive Sleep Apnea Is Closely Related to Cardiovascular Risk Factors, but
      Not to Clinical Recurrence of Atrial Fibrillation after Catheter Ablation: An
      Analysis of Atrial Fibrillation Patients.
AB  - Background: Obstructive sleep apnea (OSA) is a well-known predictor of atrial
      fibrillation (AF). However, OSA usually accompanies other risk factors of AF. We
      tried to investigate whether OSA is related to AF recurrence after catheter
      ablation. Methods: A total of 378 patients (mean age 59.9 +/- 10.7 years, 72.5$
      male) who underwent catheter ablation of AF were enrolled and underwent overnight
      ambulatory polysomnography before the ablation procedure. These patients were
      examined once every 3 months at the outpatient clinic to determine AF recurrence.
      Results: Based on the apnea-hypopnea index (AHI), we divided the study subjects
      into 3 groups defined as mild (AHI < 10), moderate (10 <AHI < 30), or severe (AHI
      > 30) OSA. Patients with severe OSA had a higher prevalence of hypertension,
      diabetes mellitus, and coronary artery disease (CAD). However, AF recurrence was
      not different between the three groups. The Kaplan-Meier analysis also showed no
      significant difference in AF recurrence according to the degree of severity of
      OSA. Multivariate logistic regression analysis revealed that OSA might be a
      predictor of CAD; however, Cox regression analysis showed that only early
      recurrence is closely related to AF recurrence after catheter ablation, rather
      than the severity of OSA. Conclusion: This study shows that the severity of OSA
      is not associated with the recurrence of AF after catheter ablation in Korean
      patients. Treatment of OSA for the sole indication of lowering AF recurrence may
      need to be reconsidered.

PMID- 30283754
TI  - Dietary Sodium Intake and Serum Uric Acid: A Mini-Review.
AB  - The aim of the present review is to summarize recent studies on the relationship
      between dietary sodium intake and serum uric acid concentration. In short-term
      dietary sodium intervention studies, including a recent further analysis of a
      previously published trial, high dietary sodium intake (200 mmol/day), compared
      with a low sodium diet (20-60 mmol/day), resulted in a significant reduction in
      serum uric acid, being approximately 20-60 MUmol/L. This finding, though
      consistent across short-term studies, is in contradiction to the long-term
      observational evidence on the relationship between dietary sodium intake and
      serum uric acid. Indeed, in a population-based prospective study, high dietary
      sodium intake was associated with a higher serum uric acid concentration. If
      serum uric acid would be followed up, several currently ongoing long-term
      randomized dietary sodium intervention studies may shed some light on how dietary
      sodium intake interacts with serum uric acid in the development of hypertension.

PMID- 30283753
TI  - Methods of Blood Pressure Assessment Used in Milestone Hypertension Trials.
AB  - In the present review, we summarized the blood pressure (BP) measurement
      protocols of contemporary outcome trials in hypertension. In all these trials,
      clinic BP was used for the diagnosis and therapeutic monitoring of hypertension.
      In most trials, BP was measured in the sitting position with mercury
      sphygmomanometers or automated electronic BP monitors by trained observers. BP
      readings were taken on each occasion at least twice with a 30-to-60-s interval
      after 5 min of rest. Details regarding the arm side, cuff size, and the timing of
      BP measurement were infrequently reported. If clinic BP continues being used in
      future hypertension trials, the measurement should strictly follow current
      guidelines. The observers must be trained and experienced, and the device should
      be validated by automated electronic BP monitors. On each occasion, BP readings
      should be taken 2-3 times. The time interval between successive measurements has
      to be 30-60 s, and the resting period before the measurement should be at least 5
      min in the supine or seated position and 1-3 min standing. BP should usually be
      measured in the seated position. The higher arm side and an appropriate size cuff
      should be chosen and noted. BP should be measured at defined trough hours.
      Automated office BP measurement has recently been used and seems to have less
      white-coat effect. The out-of-office BP measurement, either ambulatory or home BP
      monitoring, was only used in a subset of study participants of few hypertension
      trials. Future trials should consider these novel office or out-of-office BP
      measurements in guiding the therapy and preventing cardiovascular events.

PMID- 30283755
TI  - Effective Clinical Teaching Behaviors Views of Nursing Students and Nurse
      Educators at University of Gondar, Northwest Ethiopia: Cross-Sectional
      Institution Based Study.
AB  - Introduction: Clinical teaching behavior is a critical determinant for quality of
      clinical learning. Nursing students' and instructor's perception of effective
      clinical teaching behavior (ECTB) is important to modify and facilitate clinical
      education. Thus, the main purpose of this study was to assess the effective
      clinical teaching behavior (ECTB) as perceived by students and nursing
      instructors. Methods: Facility based cross-sectional descriptive study design was
      conducted among 178 participants. Data were collected using pre-tested and self
      administered questionnaire. Effective clinical teaching behaviors were measured
      by Nursing Clinical Teacher Effectiveness Inventory. Data were analyzed using
      descriptive and independent sample t-test. An adjusted odds ratio with 95%
      confidence interval computed to determine the level of significance. Results: The
      most important rated ECTB as perceived by students was teaching ability. For
      instructors, nursing competences was the most rated ECTB. The overall mean of
      ECTBs of the students and instructors were 4.26 (0.52) and 3.52 (0.74)
      respectively. There was statistically significant mean difference between them (t
      = 5.888). Conclusion: There was a statistically significant mean difference
      between the students' and instructors' perception of ECTBs. Thus, authors suggest
      nursing instructors to consider the presence of students who prefers different
      teaching methods.

PMID- 30283756
TI  - Experiences and Problems Encountered by Families of Children with Sickle Cell
      Anemia.
AB  - Introduction: Sickle Cell Anemia is a disease that has a high level of morbidity
      and early mortality for patients that are not followed and controlled properly.
      Study was conducted the aim of determining experiences and problems of families
      whose children with sickle cell anemia. Methods: Descriptive study was conducted
      the aim of determining experiences and problems of families (n= 206) whose
      children with sickle cell anemia. Before conducting this study, a written
      permission from the related institution and research ethics committee approval
      from Gaziantep University were obtained. Questionnaire is made up of two sections
      (10 questions), socio-demographic of families and data about their problems (15
      questions and 11 statements). Data were evaluated SPSS (21.0), number and
      percentage calculations. Results: It was determined that 96.1% of participants
      knew nothing about disease before their children were diagnosed, 92.7% of them
      are aware the disease was genetically inherited, all participants were a disease
      carrier themselves, and 93.7% of them had no blood tests before marriage. 97.1%
      of participants have no support from their spouses, It was determined that 98.5%
      of children suffer from pain, 60.7% suffer from weakness 51.5% of the
      participants apply to hospitals to decrease the problems and 48.5% use
      medications at home. Conclusion: A great number of families have problems
      regarding fear of losing their children, lack of social aid and support. Majority
      of children suffer from pain, weakness, exhaustion, they stay at hospital between
      at least 1 and 5 times a year, they need blood transfusion.

PMID- 30283757
TI  - Evaluation of Children Quality of Life after Serous Otitis Media Surgery.
AB  - Introduction: Otitis media with effusion is a common childhood disease diagnosed
      with the accumulation of serous fluid or mucous in the middle ear. If not
      treated, the sustainable effusion leads to change and destruction of middle ear
      structures. One of the most successful treatment methods is myringotomy and
      ventilation tube insertion, which leads to improvement of patients' quality of
      life. The aim of this study was to evaluate children's quality of life after
      inserting ventilation tubes. Methods: This prospective cross-sectional study
      examined the quality of life of the children suffering from otitis media with
      sustainable effusion, who were candidates for ventilation tube insertion. Otitis
      Media outcome-22 (OMO -22) questionnaire, was used to record the patients'
      problems in a 12-week period before and after surgery. Results: In this study, 70
      patients, including 43 (61.4%) boys and 27 (38.6%) girls (1y-13y), who completed
      the questionnaire, were studied. Treatment with ventilation tubes improved many
      physical symptoms of the hearing loss along with speech and behavioral symptoms.
      A significant reduction was observed in the number of physician visits and the
      use of antibiotics for ear problems. Conclusion: Ventilation tube insertion not
      only reduced the symptoms of otitis media with effusion, but also improved the
      children's quality of life.

PMID- 30283759
TI  - Social Support and Depression in Iranian Cancer Patients: the Role of Demographic
      Variables.
AB  - Introduction: Depression is the most frequent mental disorder in cancer patients,
      which is, unfortunately, less noticeable. Despite extensive researches, we only
      have scant knowledge about the influence of social support on depression in
      cancer patients. The aim of this study is to examine the relationship between
      perceived social support and depression and demographic variables on cancer
      patients. Methods: This is a descriptive correlational study on two hundred
      cancer patients in Isfahan, Iran. The study subjects were selected through
      convenient sampling method and data were collected using questionnaires
      (demographic questionnaire, Multidimensional Scale of Perceived Social Support
      (MSPSS) and Beck Depression Scale (BDS). Data were analyzed by SPSS software
      (Frequency distribution, Chi-Square and Spearman correlation). Results: The
      findings showed that social support and depression in cancer patients are
      significantly correlated with each other (r = - 0.785, P <0.001). Furthermore,
      the findings indicated that there are statistically significant correlations
      between degrees of education with depression and also between the numbers of
      children with social support and depression in cancer patients. For all analyses,
      was considered significant. Conclusion: In conclusion, we suggest that
      interventions to alleviate depression in cancer patients may be designed with
      consideration of demographic characteristics especially the level of education
      and the number of supporters of the patient to increase the quality of life in
      cancer patients and minimize the negative consequences of cancer diagnosis.

PMID- 30283758
TI  - The Effect of Fun Physical Activities on Sarcopenia Progression among Elderly
      Residents in Nursing Homes: a Randomized Controlled Trial.
AB  - Introduction: Immobilization in the elderly can reduce the size and strength of
      muscle mass and ultimately lead to sarcopenia, the severity and progression of
      which can be prevented by exercise. However, due to physical and mental
      conditions, the elderly may be unable to take full advantage of regular exercise.
      Therefore, fun exercise through motivation and effective participation of older
      adults is likely to have positive effects on decreasing the volume and power of
      muscle mass. The aim of this study was to determine the effect of fun physical
      activities on the progression of sarcopenia among elderly residents in nursing
      homes. Methods: This study was a two-group randomized controlled trial conducted
      in 2014. Sixty three older adults were recruited by the random sampling. The
      elderly in the fun physical exercise group did the exercise for 8 weeks, three
      times a week for 20 minutes at a time, and in the control group, the adults did
      the routine exercises. The Berg Balance Scale, a dynamometer, and the Six-Minute
      Walk Test were used to measure sarcopenia criteria (balance, muscle strength,
      distance traveled).The statistical analysis was done by SPSS version 13. Results:
      The results showed that the mean score of the sarcopenia criterion (balance,
      distance walked, muscles strength) was significantly increased in the fun
      physical exercise group than in the control group. Conclusion: The fun physical
      activity reduces sarcopenia progression through improving balance, increasing
      distances walked, and strengthening muscles.

PMID- 30283760
TI  - Improving Quality of Care in Hemodialysis: a Content Analysis.
AB  - Introduction: Hemodialysis is currently the most common alternative treatment in
      patients with renal failure in the world. Today, despite the support provided by
      healthcare providers for these patients, they still express dissatisfaction with
      the quality of care and find it inadequate. However, there have been few studies
      investigating the needs of in-patients receiving hemodialysis care in Iran. Thus
      this research was undertaken to study the needs and demands of such patients.
      Methods: This qualitative research was conducted from June to November 2016 to
      investigate the view points of the patients, their families and health care
      providers about improving quality of care in dialysis unit. At first, the
      sampling was based on a purposeful sampling method. A total of 35 participants
      (patients, their families and health care providers) were interviewed. The
      interviews were analyzed via Graneheim & Lundman qualitative content analysis.
      Results: Data analyses led to the production of 700 primary codes, 54
      subcategories and 27 secondary categories out which 4 main categories of
      modification of physical stressors, requirement of support and the requirement of
      improved quality of Health Care service and improved facilities and equipment
      requirement. Conclusion: Planning for modification of physical stressors,
      improved support of patients, enhancing the quality of care services provided by
      the treatment team, upgrading the facilities and equipment and the adoption of an
      interdisciplinary approach are all believed to improve the care services among in
      patients receiving hemodialysis treatment.

PMID- 30283761
TI  - Service Quality Gaps in the Provision of Care to Surgical Patients: a Cross
      Sectional Study in the Northwest of Iran.
AB  - Introduction: The evaluation of service quality is a key measurement which
      provides the necessary information for effective decision making and providing
      high quality care. This study aimed to investigate the factors affecting the
      service quality gap for the provision of care from the perspective of surgical
      patients hospitalized in a teaching hospital in the Northwest of Iran in 2015.
      Methods: In this descriptive cross-sectional study a total of 300 patients and
      101 nurses were selected by random sampling method. The data regarding patients'
      expectations and perceptions of the quality of healthcare services were collected
      using the SERVQUAL questionnaire. Also, the nurses' demographic data were
      assessed using the demographic data tool. Results: The mean and standard
      deviation of the patients' expectations and perceptions of the quality of
      healthcare services were 66.59)8.52) and 51.81(11.97), respectively. In all
      dimensions of the quality of healthcare services, the patients' perceptions were
      lower than their expectations. The greatest gap was observed in the dimensions of
      assurance and responsibility and the lowest gap was reported in the domains of
      reliability and empathy. There were statistically significant relationships
      between the nurses' age, work experiences in surgical wards, professional
      experiences of nurses, patients' income level and the gap in the quality of
      healthcare services. Conclusion: Despite great efforts directed at the field, the
      healthcare system still faces numerous challenges in the provision of high
      quality healthcare services to the patients. The health system should support low
      income people and employ professional and experienced nurses for improving the
      quality of healthcare services.

PMID- 30283762
TI  - The Resilient Care of Patients with Vegetative State at Home: a Grounded Theory.
AB  - Introduction: The care of patients in vegetative state at home is difficult
      because they need continuous medical interventions and extensive care. The
      present study aims to explain the process of home care of patients in vegetative
      state at home. Methods: This study was a qualitative research with a grounded
      theory approach. The participants were 22 people (included 17 family caregivers
      and 5 professional caregivers) who were enrolled in a purposive sampling. Data
      was gathered through unstructured interviews, observations and field notes. Data
      collection was continued to saturation. Data analysis was performed through the
      Strauss and Corbin 1998 approach. The MAXQDA10 software was used to facilitate
      data analysis. Results: The data analysis led to emerge four main concepts
      included "erosive care", "erosive expenditures", "seeking solver education" and
      "lasting hope" as the axes of the study. Participants' experiences showed that
      the main concern of family caregivers of vegetative patients was "playing an
      inevitable role in care", in which they did not hesitate to make any effort, and
      they tolerated all the problems and issues. Therefore, "resilient care" was
      extracted as the underlying idea of this study. Conclusion: The process of
      resilient care of vegetative patients at home showed planning by policy makers in
      health system is very important and underscored the necessity for supporting
      families and family caregivers of these patients. So some changes in the health
      system for this goal might include considering home care and supporting them in
      various aspects, especially information, financial and emotional dimensions.

PMID- 30283763
TI  - Delayed Cord Clamping Increased the Need for Phototherapy Treatment in Infants
      With AB0 Alloimmunization Born by Cesarean Section: A Retrospective Study.
AB  - Objective: To compare the effect of Delayed Cord Clamping (DCC) to Immediate Cord
      Clamping (ICC) on phototherapy treatment in a cohort of cesarean-delivered
      newborns with AB0-alloimmunization. Study Design: In a retrospective cohort study
      neonates with Gestational Age (GA) >= 35 weeks and diagnosed with AB0
      alloimmunization before implementation of DCC (ICC group) were compared with
      neonates born after implementation (DCC group). The primary outcome was the need
      for phototherapy. Secondary outcomes included hospital stay, readmission rate,
      need for extra intravenous fluids, maximum bilirubin concentration, and hours of
      life at bilirubin peak. We used regression models to adjust for weight loss, type
      of feeding, birth weight, and gestational age. Results: In total 336 neonates
      were included, of which 192 neonates in the ICC group and 144 in the DCC group.
      There were no differences in basic characteristics between the two groups except
      for birth weight (ICC 3193 +/- 468 g vs. DCC 3053 +/- 446 g, p = 0.01) and GA
      (ICC 38.2 +/- 1 weeks of GA, vs. DCC 37.9 +/- 1 weeks of GA; p = 0.01). When
      adjusted for confounding factors, after implementation of DCC, significantly more
      infants with AB0 alloimmunization needed phototherapy (22.4% vs. 36.8%, RR 1.61
      CI: 1.15-2.28; p = 0.006; Number Needed to Harm 7), needed to stay longer in
      hospital (20.3% vs. 30.5%, RR 1.53 CI: 1.05-2.23; p = 0.03). The maximum
      bilirubin was higher (11.4 +/- 4.0 mg/dl vs. 12.9 +/- 3.5 mg/dl, p < 0.001) and
      occurred later [74 (67-92) hours vs. 84 (70-103) hours; p = 0.04]. There was no
      difference in the need for intravenous fluids (1.6% vs. 4.9%; not significant)
      and readmissions (1.6% vs. 3.5%; not significant). Conclusion: Infants with AB0
      alloimmunization needed more often phototherapy and were admitted longer after
      implementation of DCC policy. Further studies are needed to see whether the
      benefit of DCC outweighs the increased morbidity, admission days, and related
      hospital costs.

PMID- 30283764
TI  - Weight Loss Surgery Utilization in Patients Aged 14-25 With Severe Obesity Among
      Several Healthcare Institutions in the United States.
AB  - Introduction: Obesity is associated with early co-morbidities and higher
      mortality. Even though weight loss surgery (WLS) in adolescents with severe
      obesity reliably achieves safe and lasting improvement in BMI and superior
      resolution of comorbid diseases, its utilization among young patients in the
      clinical practice stands unclear. Objective: To show the prevalence of weight
      loss surgery utilization rates in adolescents and young adults among several
      healthcare institutions in the United States. Method: WLS in 14-25 years old
      between 2000 and 2017 was obtained from Washington University, Morehouse Medical,
      University of Texas, Wake Forest Baptist Medical Center, Beth Israel Deaconess
      Medical Center, Boston Children's Hospital, Boston Medical Center, and Partners
      Healthcare using the Shared Health Research Information Network (SHRINE) and
      Research Patient Data Registry (RPDR) web-based query tools. ICD-9 codes were
      used for bariatric surgery. Results: Among 2500635 individuals, 18008 (0.7%) had
      severe obesity. At Partners, 1879 patients had severe obesity, of which 404
      (21.5%) underwent WLS, whereas at Washington University, 44 (2.5%) of 1788 the
      underwent WLS. 13 (2.3%) of the 575 at BIDMC, 43 (1.5%) of the 2969 at BMC, and
      37 (0.4%) of 8908 at BCH underwent WLS (p < 0.0001 for all). Discussion: Even
      though WLS has shown to be the most effective treatment to create sustainable
      changes in metabolic derangements for moderate to severe obesity and its
      comorbidities, it has been underutilized. Further studies need to be conducted to
      ensure WLS is utilized for those patients who would achieve the most benefit.

PMID- 30283765
TI  - Indirect Calorimetry: History, Technology, and Application.
AB  - Measurement of energy expenditure is important in order to determine basal
      metabolic rate and inform energy prescription provided. Indirect calorimetry is
      the reference standard and clinically recommended means to measure energy
      expenditure. This article reviews the historical development, technical, and
      logistic challenges of indirect calorimetry measurement, and provides case
      examples for practicing clinicians. Formulae to estimate energy expenditure are
      highly inaccurate and reinforce the role of the indirect calorimetry and the
      importance of understanding the strength and limitation of the method and its
      application.

PMID- 30283766
TI  - The Relative Roles of Peer and Parent Predictors in Minor Adolescent Delinquency:
      Exploring Gender and Adolescent Phase Differences.
AB  - Social learning theories assume that delinquent peer norms and/or peer pressure
      are the components of delinquent peer socialization that lead to subsequent
      adolescent delinquency. However, these specific peer influences are rarely
      investigated. Moreover, social learning theories such as coercion theory posit
      that parenting behaviors also play an important role in the development or
      prevention of delinquency. However, surprisingly, little research has
      investigated whether parent behaviors could moderate the link between the above
      described peer influences and adolescent delinquency. Hence, using structural
      equation modeling, the current 1-year longitudinal study investigated these
      questions among ethnically-diverse Dutch adolescents (N = 602; M age = 13.50;
      46.42% female at baseline), who were mostly between12 and 15 years old.
      Additionally, using multi-group models, and a stringent p-value of p < 0.01, we
      explored whether gender and adolescent phase (i.e., early versus middle
      adolescence) further moderated these links. The majority of the analyses,
      resulted in non-significant findings. Specifically, in our non-multi group model,
      we found no significant peer, and family effects for the entire sample. However,
      for our multi-group models, we found that higher levels of negative mother
      adolescent relationship quality exacerbated the link between peer pressure and
      subsequent early adolescent boys' delinquency 1 year later, while low levels of
      mother-adolescent negative relationship quality reversed the association. That
      is, low levels of mother-adolescent negative relationship quality attenuated the
      link from higher levels of peer pressure to higher levels of delinquency, but
      only in early adolescent boys. These findings existed above and beyond
      significant links from prior adolescent delinquency (T1) to future adolescent
      delinquency (T2). To conclude, although this was not the case for most
      adolescents, for early adolescent boys fewer negative interactions between mother
      and adolescents at an earlier time point (in advance) could potentially curtail
      the negative effects that delinquent peer pressure has on delinquency in the
      future. Implications for theory and practice are discussed.

PMID- 30283767
TI  - Effect of a Health Coach Intervention for the Management of Individuals With Type
      2 Diabetes Mellitus in China: A Pragmatic Cluster Randomized Controlled Trial.
AB  - : Aim: To determine the effect of a health coach intervention for the management
      of glycemic control, as well as physiological, psychological and self-care
      outcomes of patients with type 2 diabetes mellitus (T2DM), compared with usual
      care. Methods: This pragmatic cluster RCT was conducted in the Fengtai district
      of Beijing from August 2011 to December 2013. Forty-one community health stations
      (CHSs) were cluster randomized (stratified geographically, 1:1 ratio) and
      eligible, randomly selected T2DM patients were sequentially contacted by CHSs.
      Control participants received usual care according to the Chinese Guideline for
      Diabetes Prevention and Management. Intervention participants received 18-months
      of health coaching based on principles of Motivational Interviewing (MI) plus
      usual care. Medical and pathology fees were waived for both groups. Outcome
      assessment was performed at baseline, 6, 12, and 18-months. The primary outcome
      was glycated hemoglobin (HbA1c); secondary outcomes encompassed a suite of
      physiological, psychological and self-care measures. Results: No differential
      treatment effect was found at 18-months for HbA1c (adj. difference -0.07, 95% CI 
      0.53 to 0.39, p = 0.769) or any specified secondary outcomes. Interestingly, both
      groups displayed a statistically and clinically significant within-group
      improvement of the same magnitude at 18-months for HbA1c (intervention: mean
      change -3.65, 95% CI -3.92 to -3.37; control: mean change -3.38, 95% CI -3.67 to 
      3.08). Conclusions: The lack of differential treatment effects observed indicate
      that it may be premature to recommend the routine delivery of health coach
      interventions based on MI principles for the management of T2DM in China.
      However, the large, comparable within-group improvement in mean HbA1c promotes
      the establishment of free, regular clinical health assessments for individuals
      with T2DM in China. TRIAL REGISTRATION: ISRCTN registry - ISRCTN01010526
      (https://doi.org/10.1186/ISRCTN01010526).

PMID- 30283768
TI  - Field Epidemiology and Laboratory Training Program, Where Is the L-Track?
AB  - Background: Modifications of the Field Epidemiology Training Program (FETP)
      curricula to include a laboratory track (L-Track), to become Field Epidemiology
      and Laboratory Training Program (FELTP), began in 2004 in Kenya. The L-Track
      offered candidates training on laboratory competencies in management, policy,
      quality systems, and diagnostic methods as well as epidemiology, disease
      surveillance and outbreak response. Since then several FELTPs have discontinued
      the L-Track and instead offer all candidates, epidemiologists and laboratorians,
      a single FETP curriculum. Reasons for these changes are reported here. Methods: A
      questionnaire was sent to directors of 13 FELTP programs collecting information
      on the status of the programs, reasons for any changes, basic entry
      qualifications, source institutions and where residents were post enrollment or
      after graduation. Data from previous CDC internal assessments on FELTP L-Track
      was also reviewed. Results: Out of the 13 FELTPs included, directors from 10
      FELTPs sent back information on their specific programs. The FELTPs in Kenya,
      Mozambique, Cameroon and Kazakhstan and Mali have discontinued a separate L-Track
      while those in Ghana, Georgia, Nigeria, Rwanda, and Tanzania continue to offer
      the separate L-Track. Reasons for discontinuation included lack of standardized
      curriculum, unclear strategies of the separate L-Track, and funding constraints.
      Two countries Kenya and Tanzania reported on the career progression of their
      graduates. Results show 84% (Kenya) and 51% (Tanzania) of candidates in the
      FELTP, L-Track were recruited from national/regional medical health laboratories.
      However post-graduation, 56% (Kenya) and 43% (Tanzania) were working as
      epidemiologists, program managers, program coordinators, or regulatory/inspection
      boards. Professional upward mobility was high; 87% (Kenya) and 73% (Tanzania)
      residents, reported promotions either in the same or in new institutions.
      Conclusions: The FELTP L-Track residents continue to offer critical contributions
      to public health workforce development with high upward mobility. While this may
      be a reflection of professional versatility and demand of the FELTP graduates,
      the move from core laboratory services underscores the challenges in filling and
      retaining qualified staff within the laboratory systems. Results suggest
      different strategies are needed to strengthen laboratory management and
      leadership programs with a clear focus on laboratory systems and laboratory
      networks to meet current and future clinical and public health laboratory
      workforce demands.

PMID- 30283769
TI  - Editorial: Toxicity of Pesticides on Health and Environment.

PMID- 30283770
TI  - Porous NaTi2(PO4)3 Nanocubes Anchored on Porous Carbon Nanosheets for High
      Performance Sodium-Ion Batteries.
AB  - NaTi2(PO4)3 has attracted great interest as anode material for sodium ion
      batteries owing to its open three-dimensional framework structure and limited
      volume changes during the charge and discharge process. However, the poor
      intrinsic electronic conductivity of NaTi2(PO4)3 needs to be improved for high
      rate capability. In this work, porous NaTi2(PO4)3 nanocubes anchored on porous
      carbon nanosheets (NaTi2(PO4)3/C) are designed and developed. This material
      exhibits a large discharge capacity and good rate capacity including a first
      discharge capacity of 485 mAh g-1 at a current density of 0.1 A g-1, and 98 mAh g
      1 retained at a high rate of 4 A g-1 even after 2,000 cycles. These results
      suggest that NaTi2(PO4)3/C is a promising anode material for sodium-ion
      batteries.

PMID- 30283771
TI  - Pickering Emulsions Electrostatically Stabilized by Cellulose Nanocrystals.
AB  - Cellulose Nanocrystals (CNC) are explored to stabilize oil/water emulsions for
      their ability to adsorb at the oil/water interface. In this work, the role of
      electrostatic forces in the CNC ability to stabilize oil/water emulsions is
      explored using canola oil/water and hexadecane/water as model systems. Canola
      oil/water and Hexadecane/ water (20/80, v/v) emulsions were stabilized with the
      addition of CNCs using ultrasonication. Emulsion droplet sizes range from 1 to 4
      MUm as measured by optical microscopy. It is found that CNC can stabilize
      oil/water emulsions regardless of their charge density. However, reducing the
      surface charge density, by adding salts and varying pH, can reduce the amount of
      CNC's required to form a stable emulsion. Just by adding 3 mM Na+ or 1 mM or less
      Ca+2 to a CNC suspension, the amount of CNC reduced by 30% to stabilized 2 mL of
      Canola oil. On the other hand, adding salt increases the emulsion volume. The
      addition of 100 mM Na+ or the reduction of pH below 2 leads to the aggregation of
      CNC; emulsions formed under these conditions showed gel-like behavior. This work
      shows the potential of nanocellulose crystal in stabilizing food and industrial
      emulsions. This is of interest for applications where biodegradability,
      biocompatibility, and food grade requirements are needed.

PMID- 30283773
TI  - Adsorption and Photocatalytic Processes of Mesoporous SiO2-Coated Monoclinic
      BiVO4.
AB  - The silicon dioxide (SiO2)-coated bismuth vanadate (BiVO4) composites as visible
      driven-photocatalysts were successfully synthesized by the co-precipitation
      method. The effects of SiO2 coating on the structure, optical property,
      morphology and surface properties of the composites were investigated by X-ray
      diffraction (XRD), UV-visible diffuse reflectance spectroscopy (DRS),
      transmission electron microscopy (TEM) and Brunauer-Emmette-Teller (BET)
      measurements. The photocatalytic activity of monoclinic BiVO4 and BiVO4/SiO2
      composites were evaluated according to the degradation of methylene blue (MB) dye
      aqueous solution under visible light irradiation. The SiO2-coated BiVO4
      composites showed the enhancing photocatalytic activity approximately threefold
      in comparison with the single phase BiVO4.

PMID- 30283772
TI  - Small-Molecule Electron Acceptors for Efficient Non-fullerene Organic Solar
      Cells.
AB  - The development of organic electron acceptor materials is one of the key factors
      for realizing high performance organic solar cells. Compared to traditional
      fullerene acceptor materials, non-fullerene electron acceptors have attracted
      much attention due to their better optoelectronic tunabilities and lower cost as
      well as higher stability. Non-fullerene organic solar cells have recently
      experienced a rapid increase with power conversion efficiency of single-junction
      devices over 14% and a bit higher than 15% for tandem solar cells. In this
      review, two types of promising small-molecule electron acceptors are discussed:
      perylene diimide based acceptors and acceptor(A)-donor(D)-acceptor(A) fused-ring
      electron acceptors, focusing on the effects of structural modification on
      absorption, energy levels, aggregation and performances. We strongly believe that
      further development of non-fullerene electron acceptors will hold bright future
      for organic solar cells.

PMID- 30283774
TI  - The Impact of Cr3+ Doping on Temperature Sensitivity Modulation in Cr3+ Doped and
      Cr3+, Nd3+ Co-doped Y3Al5O12, Y3Al2Ga3O12, and Y3Ga5O12 Nanothermometers.
AB  - A new approach to enhance the sensitivity of transition metal ion based
      nanocrystalline luminescent thermometer is presented. It was shown that the
      increase of Cr3+ concentration in three types of garnet host namely Y3Al5O12,
      Y3Ga5O12, and Y3Al2Ga3O12 allows for significant enhancement of their performance
      in non-contact thermometry. This phenomenon is related to the weakening of the
      crystal field strength due to enlargement of average Cr3+-O2- distance at higher
      Cr3+ concentrations. By increasing Cr3+ concentration from 0.6 to 30%, the
      sensitivity increased by over one order of magnitude from S = 0.2%/ degrees C to
      S = 2.2%/ degrees C at 9 degrees C in Y3Al2Ga3O12 nanocrystals. Moreover, it was
      found that due to the Cr3+ -> Nd3+ energy transfer in the Cr3+, Nd3+ co-doped
      system, the usable Cr3+ concentration, for which its emission can be detected, is
      limited to 10% while the sensitivity at -50 degrees C was doubled (from 1.3%/
      degrees C for Y3Al2Ga3O12:10%Cr3+ to 2.2%/ degrees C Y3Al2Ga3O12:10%Cr3+, 1%Nd3+
      nanocrystals).

PMID- 30283775
TI  - Microwave-Assisted Knoevenagel-Doebner Reaction: An Efficient Method for
      Naturally Occurring Phenolic Acids Synthesis.
AB  - The common chemical method to synthesize Phenolic Acids (PAs) involves a
      relatively considerable energy intake. In order to solve this issue, microwave
      assisted Knoevenagel-Doebner condensations were developed. Nevertheless, these
      synthetic procedures prove difficult to reproduce. Herein, we developed and
      optimized-by using a combination of a Design of Experiment and a standard
      optimization approach-a reliable procedure that converts naturally occuring p
      hydroxybenzaldehydes into the corresponding PAs with conversions of 86-99% and in
      85-97% yields.

PMID- 30283776
TI  - Photocrosslinkable Gelatin Hydrogels Modulate the Production of the Major Pro
      inflammatory Cytokine, TNF-alpha, by Human Mononuclear Cells.
AB  - Hydrogels are an attractive class of biomaterials in tissue engineering due to
      their inherently compatible properties for cell culture. Gelatin methacryloyl
      (GelMA) has shown significant promise in the fields of tissue engineering and
      drug delivery, as its physical properties can be precisely tuned depending on the
      specific application. There is a growing appreciation for the interaction between
      biomaterials and cells of the immune system with the increasing usage of
      biomaterials for in vivo applications. Here, we addressed the current lack of
      information regarding the immune-modulatory properties of photocrosslinked GelMA.
      We investigated the ability of human mononuclear cells to mount inflammatory
      responses in the context of a GelMA hydrogel platform. Using lipopolysaccharide
      to stimulate a pro-inflammatory immune response, we found tumor necrosis factor
      alpha (TNF-alpha) expression was suppressed in GelMA culture conditions. Our
      findings have important implications on the future use of GelMA, and potentially
      similar hydrogels, and highlight the significance of investigating the potential
      immune-modulatory properties of biomaterials.

PMID- 30283777
TI  - An Efficient Modelling-Simulation-Analysis Workflow to Investigate Stump-Socket
      Interaction Using Patient-Specific, Three-Dimensional, Continuum-Mechanical,
      Finite Element Residual Limb Models.
AB  - The lack of an efficient modelling-simulation-analysis workflow for creating and
      utilising detailed subject-specific computational models is one of the key
      reasons why simulation-based approaches for analysing socket-stump interaction
      have not yet been successfully established. Herein, we propose a novel and
      efficient modelling-simulation-analysis workflow that uses commercial software
      for generating a detailed subject-specific, three-dimensional finite element
      model of an entire residual limb from Diffusion Tensor MRI images in <20 min.
      Moreover, to complete the modelling-simulation-analysis workflow, the generated
      subject-specific residual limb model is used within an implicit dynamic FE
      simulation of bipedal stance to predict the potential sites of deep tissue
      injury. For this purpose, a nonlinear hyperelastic, transversely isotropic
      skeletal muscle constitutive law containing a deep tissue injury model was
      implemented in LS-DYNA. To demonstrate the feasibility of the entire modelling
      simulation-analysis workflow and the fact that detailed, anatomically realistic,
      multi-muscle models are superior to state-of-the-art, fused-muscle models, an
      implicit dynamic FE analysis of 2-h bipedal stance is carried out. By analysing
      the potential volume of damaged muscle tissue after donning an optimally-fitted
      and a misfitted socket, i.e., a socket whose volume was isotropically shrunk by
      10%, we were able to highlight the differences between the detailed individual-
      and fused-muscle models. The results of the bipedal stance simulation showed that
      peak stresses in the fused-muscle model were four times lower when compared to
      the multi-muscle model. The peak interface stress in the individual-muscle model,
      at the end of bipedal stance analysis, was 2.63 times lower than that in the deep
      tissues of the stump. At the end of the bipedal stance analysis using the
      misfitted socket, the fused-muscle model predicted that 7.65% of the residual
      limb volume was injured, while the detailed-model predicted 16.03%. The proposed
      approach is not only limited to modelling residual limbs but also has
      applications in predicting the impact of plastic surgery, for detailed forward
      dynamics simulations of normal musculoskeletal systems.

PMID- 30283778
TI  - Validating the RedMIT/GFP-LC3 Mouse Model by Studying Mitophagy in Autosomal
      Dominant Optic Atrophy Due to the OPA1Q285STOP Mutation.
AB  - Background: Autosomal dominant optic atrophy (ADOA) is usually caused by
      mutations in the essential gene, OPA1. This encodes a ubiquitous protein involved
      in mitochondrial dynamics, hence tissue specificity is not understood.
      Dysregulated mitophagy (mitochondria recycling) is implicated in ADOA, being
      increased in OPA1 patient fibroblasts. Furthermore, autophagy may be increased in
      retinal ganglion cells (RGCs) of the OPA1Q285STOP mouse model. Aims: We developed
      a mouse model for studying mitochondrial dynamics in order to investigate
      mitophagy in ADOA. Methods: We crossed the OPA1Q285STOP mouse with our RedMIT/GFP
      LC3 mouse, harboring red fluorescent mitochondria and green fluorescent
      autophagosomes. Colocalization between mitochondria and autophagosomes, the
      hallmark of mitophagy, was quantified in fluorescently labeled organelles in
      primary cell cultures, using two high throughput imaging methods Imagestream
      (Amnis) and IN Cell Analyzer 1000 (GE Healthcare Life Sciences). We studied
      colocalization between mitochondria and autophagosomes in fixed sections using
      confocal microscopy. Results: We validated our imaging methods for RedMIT/GFP-LC3
      mouse cells, showing that colocalization of red fluorescent mitochondria and
      green fluorescent autophagosomes is a useful indicator of mitophagy. We showed
      that colocalization increases when lysosomal processing is impaired. Further,
      colocalization of mitochondrial fragments and autophagosomes is increased in
      cultures from the OPA1Q285STOP/RedMIT/GFP-LC3 mice compared to RedMIT/GFP-LC3
      control mouse cells that were wild type for OPA1. This was apparent in both mouse
      embryonic fibroblasts (MEFs) using IN Cell 1000 and in splenocytes using
      ImageStream imaging flow cytometer (Amnis). We confirmed that this represents
      increased mitophagic flux using lysosomal inhibitors. We also used microscopy to
      investigate the level of mitophagy in the retina from the OPA1Q285STOP/RedMIT/GFP
      LC3 mice and the RedMIT/GFP-LC3 control mice. However, the expression levels of
      fluorescent proteins and the image signal-to-background ratios precluded the
      detection of colocalization so we were unable to show any difference in
      colocalization between these mice. Conclusions: We show that colocalization of
      fluorescent mitochondria and autophagosomes in cell cultures, but not fixed
      tissues from the RedMIT/GFP-LC3, can be used to detect mitophagy. We used this
      model to confirm that mitophagy is increased in a mouse model of ADOA. It will be
      useful for cell based studies of diseases caused by impaired mitochondrial
      dynamics.

PMID- 30283780
TI  - The Actin Cytoskeleton: A Mechanical Intermediate for Signal Integration at the
      Immunological Synapse.
AB  - The immunological synapse (IS) is a specialized structure that serves as a
      platform for cell-cell communication between a T cell and an antigen-presenting
      cell (APC). Engagement of the T cell receptor (TCR) with cognate peptide-MHC
      complexes on the APC activates the T cell and instructs its differentiation.
      Proper T cell activation also requires engagement of additional receptor-ligand
      pairs, which promote sustained adhesion and deliver costimulatory signals. These
      events are orchestrated by T cell actin dynamics, which organize IS components
      and facilitate their signaling. The actin network flows from the edge of the cell
      inward, driving the centralization of TCR microclusters and providing the force
      to activate the integrin LFA-1. We recently showed that engagement of LFA-1 slows
      actin flow, and that this affects TCR signaling. This study highlights the
      physical nature of the IS, and contributes to a growing appreciation in the field
      that mechanosensing and mechanotransduction are essential for IS function.
      Additionally, it is becoming clear that there are multiple types of actin
      structures at the IS that promote signaling in distinct ways. How the different
      actin structures contribute to force production and mechanotransduction is just
      beginning to be explored. In this Perspective, we will feature recent work from
      our lab and others, that collectively points toward a model in which actin
      dynamics drive mechanical signaling and receptor crosstalk during T cell
      activation.

PMID- 30283781
TI  - Isolation and Characterization of Multipotent CD24+ Cells From the Renal Papilla
      of Swine.
AB  - Over 100,000 patients in the United States are currently waiting for a kidney
      transplant. With just over 10,000 cadaveric kidneys transplanted annually, it is
      of the utmost importance to optimize kidney viability upon transplantation. One
      exciting avenue may be xenotransplantation, which has rejuvenated interest after
      advanced gene editing techniques have been successfully used in swine.
      Simultaneously, acute kidney injury (AKI) is associated with high morbidity and
      mortality and currently lacks effective treatment. Animal models have been used
      extensively to address both of these issues, with recent emphasis on renal
      progenitor cells (RPCs). Due to anatomical similarities to humans we aimed to
      examine progenitor cells from the renal papillae of swine kidneys. To do this,
      RPCs were dissected from the renal papillae of healthy swine. Cell surface marker
      expression, proliferation, and differentiation of the RPCs were tested in vitro.
      Additionally, a mixed lymphocyte reaction was performed to examine
      immunomodulatory properties. RPCs displayed spindle shaped morphology with
      limited self-renewing capacity. Isolated RPCs were positive for CD24 and CD133 at
      early passages, but lost expression with subsequent passaging. Similarly, RPCs
      displayed myogenic, osteogenic, and adipogenic differentiation capacities at
      passage 2, but largely lost this by passage 6. Lastly, direct contact of RPCs
      with human lymphocytes increased release of IL6 and IL8. Taken together, RPCs
      from the papilla of porcine kidneys display transient stem cell properties that
      are lost with passaging, and either represent multiple types of progenitor cells,
      or a multipotent progenitor population. In instances of ischemic insult,
      augmentation of/with RPCs may potentiate regenerative properties of the kidney.
      While the use of swine for transplantation and ischemia studies confers obvious
      advantages, the populations of different progenitor cell populations within pig
      kidneys warrants further investigation. Ultimately, while gene editing techniques
      enhance the potential for xenotransplantation of organs or cells, the ultimate
      success of this strategy may be determined by the (dis)similarities of RPCs from
      different species.

PMID- 30283783
TI  - Editorial: Less and Non-invasive Hemodynamic Monitoring Techniques.

PMID- 30283779
TI  - Leveraging Zebrafish to Study Retinal Degenerations.
AB  - Retinal degenerations are a heterogeneous group of diseases characterized by
      death of photoreceptors and progressive loss of vision. Retinal degenerations are
      a major cause of blindness in developed countries (Bourne et al., 2017; De Bode,
      2017) and currently have no cure. In this review, we will briefly review the
      latest advances in therapies for retinal degenerations, highlighting the current
      barriers to study and develop therapies that promote photoreceptor regeneration
      in mammals. In light of these barriers, we present zebrafish as a powerful model
      to study photoreceptor regeneration and their integration into retinal circuits
      after regeneration. We outline why zebrafish is well suited for these analyses
      and summarize the powerful tools available in zebrafish that could be used to
      further uncover the mechanisms underlying photoreceptor regeneration and
      rewiring. In particular, we highlight that it is critical to understand how
      rewiring occurs after regeneration and how it differs from development. Insights
      derived from photoreceptor regeneration and rewiring in zebrafish may provide
      leverage to develop therapeutic targets to treat retinal degenerations.

PMID- 30283782
TI  - Neprilysin Inhibitors and Bradykinin.
AB  - Bradykinin has important physiological actions related to the regulation of blood
      vessel tone and renal function, and protection from ischemia reperfusion injury.
      However, bradykinin also contributes to pathological states such as angioedema
      and inflammation. Bradykinin is metabolized by many different peptidases that
      play a major role in the control of bradykinin levels. Peptidase inhibitor
      therapies such as angiotensin converting enzyme (ACE) and neprilysin inhibitors
      increase bradykinin levels, and the challenge for such therapies is to achieve
      the beneficial cardiovascular and renal effects without the adverse consequences
      such as angioedema that may result from increased bradykinin levels. Neprilysin
      also metabolizes natriuretic peptides. However, despite the potential therapeutic
      benefit of increased natriuretic peptide and bradykinin levels, neprilysin
      inhibitor therapy has only modest efficacy in essential hypertension and heart
      failure. Initial attempts to combine neprilysin inhibition with inhibition of the
      renin angiotensin system led to the development of omapatrilat, a drug that
      combines ACE and neprilysin inhibition. However, omapatrilat produced an
      unacceptably high incidence of angioedema in patients with hypertension (2.17%)
      in comparison with the ACE inhibitor enalapril (0.68%), although angioedema
      incidence was less in patients with heart failure with reduced ejection fraction
      (HFrEF) treated with omapatrilat (0.8%), and not different from that for
      enalapril therapy (0.5%). More recently, LCZ696, a drug that combines angiotensin
      receptor blockade and neprilysin inhibition, was approved for the treatment of
      HFrEF. The approval of LCZ696 therapy for HFrEF represents the first approval of
      long-term neprilysin inhibitor administration. While angioedema incidence was
      acceptably low in HFrEF patients receiving LCZ696 therapy (0.45%), it remains to
      be seen whether LCZ696 therapy for other conditions such as hypertension is also
      accompanied by an acceptable incidence of angioedema.

PMID- 30283784
TI  - Changing Antimicrobial Resistance Trends in Kathmandu, Nepal: A 23-Year
      Retrospective Analysis of Bacteraemia.
AB  - A comprehensive longitudinal understanding of the changing epidemiology of the
      agents causing bacteraemia and their AMR profiles in key locations is crucial for
      assessing the progression and magnitude of the global AMR crisis. We performed a
      retrospective analysis of routine microbiological data from April 1992 to
      December 2014, studying the time trends of non-Salmonella associated bacteraemia
      at a single Kathmandu healthcare facility. The distribution of aetiological
      agents, their antimicrobial susceptibility profiles, and the hospital ward of
      isolation were assessed. Two hundred twenty-four thousand seven hundred forty-one
      blood cultures were performed over the study period, of which, 30,353 (13.5%)
      exhibited growth for non-contaminant bacteria. We observed a significant
      increasing trend in the proportion of MDR non-Salmonella Enterobacteriaceae (p <
      0.001), other Gram-negative organisms (p = 0.006), and Gram-positive organisms (p
      = 0.006) over time. Additionally, there was an annual increasing trend in the
      proportion of MDR organisms in bacteria-positive blood cultures originating from
      patients attending the emergency ward (p = 0.006) and the outpatient department
      (p = 0.006). This unique dataset demonstrates that community acquired non
      Salmonella bacteraemia has become an increasingly important cause of hospital
      admission in Kathmandu. An increasing burden of bacteraemia associated with MDR
      organisms in the community underscores the need for preventing the circulation of
      MDR bacteria within the local population.

PMID- 30283785
TI  - Airway Management During Anesthetic Induction of Secondary Laryngectomy for
      Recurrent Laryngeal Cancer: Three Cases of Report and Analysis.
AB  - Surgery for laryngeal cancer and the following recurrent tumor growth may further
      change the anatomy of the airway. Airway management during anesthesia induction
      is challenging for the patients undergoing secondary surgery due to recurrence of
      laryngeal cancer or its postoperative complication, but it has never been
      reported. In this report, we described three cases of anesthetic induction which
      had different process of airway events. The first case was given intravenous
      general anesthetic for induction and experienced failed intubation, difficult
      mask ventilation and emergent tracheostomy, eventually were rescued successfully.
      The second case presented a fixed metastatic mass about 6 cm diameter upon the
      primary surgical scar of incision and preoperative apnea, underwent fibroscopy
      guided conscious intubation and the process was uneventful. The third case had
      erythema and swelling under the mandible with erupted ulcer as well as neck
      immobility due to recurrent tumor. The anesthesiologist attempted fibroscopy
      guided intubation via nasal passage with a tracheal tube in 2.8 mm diameter but
      it was failed. Subsequently, tracheostomy was performed under bilateral
      superficial cervical plexus block and the dissected larynx by operation verified
      distorted structure of glottis with S-shaped stenosis. This report concludes
      that, during the anesthetic induction for this special type of surgery, a
      detailed and comprehensive evaluation of the airway, and a routine fibroscopic
      examination are especially important.

PMID- 30283786
TI  - The Hop Polyphenols Xanthohumol and 8-Prenyl-Naringenin Antagonize the Estrogenic
      Effects of Fusarium Mycotoxins in Human Endometrial Cancer Cells.
AB  - The Fusarium toxin zearalenone (ZEN) and its reductive metabolite alpha
      zearalenol (alpha-ZEL) are well-documented endocrine disruptors that are
      frequently found to contaminate cereal products, including beer. But also hop is
      known to represent a source for endocrine active compounds, containing amongst
      others xanthohumol (XAN), which might be converted to the potent phytoestrogen 8
      prenylnaringenin (8-PN). In the present study, we investigated the interaction of
      these xenoestrogens in mixtures which might occur in beer. Estrogenicity was
      measured as induction of alkaline phosphatase (AlP) expression in estrogen
      sensitive Ishikawa cells. In binary combinations, XAN was found to act as a
      potent antagonist of mycotoxin-induced estrogenicity, significantly suppressing
      the AlP-inducing impact of both ZEN and alpha-ZEL at nanomolar concentrations.
      Also 8-PN antagonized the estrogenic stimulus of the two fungal metabolites,
      although less pronounced. These effects also manifested in combinations of three
      or four test compounds, and at the level of cell proliferation, that was assessed
      via an E-screen-like approach in Ishikawa cells. Of note, co-exposure to the
      investigated myco- and phyto-estrogens did not result in additive or
      overadditive/synergistic estrogenic effects in the applied test system. Being
      aware that the actual study is still limited to the in vitro situation, our
      results even suggest that prenylated chalkones from hops might protect against
      Fusarium toxin-induced endocrine disruptive activities at concentrations that can
      be reached by moderate beer consumption.

PMID- 30283787
TI  - Neoadjuvant Chemotherapy in Patients With Muscle-Invasive Bladder Cancer and Its
      Impact on Surgical Morbidity and Oncological Outcomes: A Real-World Experience.
AB  - Objectives: The purpose of this study was to investigate the impact of
      neoadjuvant chemotherapy (NAC) on perioperative morbidity and on oncological
      outcomes according to the type of chemotherapy regimen administered to patients
      with muscle-invasive bladder cancer (MIBC) who subsequently underwent radical
      cystectomy (RC). Methods: Data were collected retrospectively on 40 patients with
      bladder urothelial carcinoma who had at least two cycles of NAC, followed by RC,
      from 2011 to 2015 at our institution. The outcomes evaluated were NAC toxicity,
      perioperative complications, cancer-specific, and overall survival. Results:
      Among these cases, 23 patients (57.5%) received methotrexate, vinblastine,
      doxorubicin and cisplatin (MVAC), 4 patients (10%) received gemcitabine and
      cisplatin (GC), and 13 patients (32.5%) received other regimes. The early and
      late postoperative complication rates were 35% and 12.5%. Regarding toxicity, 85%
      of patients had at least one side effect of NAC, but only 21.7% discontinued
      therapy in the MVAC group. The pathological complete response (pCR) rates for
      cisplatin-based regimens (MVAC and GC) and other regimens were 44.4 and 15.4%,
      respectively, (p = 0.09). The pathological partial response (pPR) rates for
      cisplatin-based regimens and other regimens were 66.7 and 15.4%, respectively, (p
      = 0.002). Patients treated with a cisplatin-based chemotherapy regimen had longer
      overall survival than those treated with other regimen (median 38.1 vs. 18.4
      months, p = 0.01). Conclusions: NAC administration was not associated with high
      toxicity or surgical morbidity. The pathological response rates and survival
      outcomes in the cisplatin-based regimens were higher than with those with non
      cisplatin-based regimens. These data support the use, in patients elective to a
      neoadjuvant setting prior to RC for MBIC, of a cisplatin-based regimen.

PMID- 30283791
TI  - Editorial: Extracellular Vesicle-Mediated Processes in Cardiovascular Diseases.

PMID- 30283790
TI  - Transcatheter Tricuspid Valve Replacement: Principles and Design.
AB  - Tricuspid regurgitation (TR) may affect as much as 65-85% of the population with
      the prevalence of moderate-to-severe TR in the United States reported at greater
      than 1.6 million. However, only 8,000 tricuspid valve operations are performed
      annually in the United States. As severe TR is associated with poor outcomes,
      there is an unmet clinical need for surgical or percutaneous transcatheter based
      treatment of TR. Over the last two decades there have been significant
      developments in percutaneous transcatheter based therapies for valvular disease.
      However, this progress has not been mirrored for the tricuspid valve until
      recently; we are now at a cross-roads of new transcatheter devices becoming
      available for treatment of TR. In this review, we discuss the principles of
      performing transcatheter tricuspid valve replacement, analyze the devices that
      can be utilized and outline the challenges related to this procedure.

PMID- 30283792
TI  - Development of the Tonsil Microbiome in Pigs and Effects of Stress on the
      Microbiome.
AB  - Tonsils, lympho-epithelial tissues located at the junction of the oropharynx and
      nasopharynx, play a key role in surveillance, colonization, and persistence of
      inhaled and ingested pathogens. In pigs, the tonsils are a reservoir for numerous
      bacteria and viruses, including host-specific pathogens and potential zoonotic
      pathogens as well as commensal organisms. However, there are no in depth studies
      of the development of the tonsillar microbiome in pigs, or any mammal, over time.
      The goal of this study was to follow the development of the tonsil microbiome in
      healthy pigs from birth to market weight. Samples were collected using tonsil
      brushes from 16 piglets (4 each from 4 sows) at newborn, 1, 2, 3, and 4 weeks of
      age, and from 8 of those piglets at 6, 8, 10, 12, 16, and 19 weeks of age.
      Bacterial DNA was isolated from each sample and 16S rDNA genes were amplified and
      sequenced. Sequence analysis showed that members of the Streptococcaceae,
      Pasteurellaceae, and Moraxellaceae were present at all time points and represent
      the three most abundant families identified. Other community members appeared
      transiently or increased or decreased significantly with disruption events or
      stress. We observed four significant shifts in the tonsil community that
      coincided with well-defined disruption events: weaning plus addition of Carbadox
      plus movement to the nursery at week 3, removal of Carbadox and addition of Tylan
      at week 5, removal of Tylan and habitat change at week 9, and habitat change at
      week 16. Weaning triggered a bloom of Streptococcaeae and decrease of
      Moraxellaceae. The shift from Carbadox to Tylan led to reduction in
      Proteobacteria and Streptococcaceae but an increase in other Firmicutes,
      accompanied by a dramatic increase in community richness. Cessation of Tylan
      coincided with a return to a less rich community, and a bloom in Clostridiales.
      The final shift in habitat was accompanied by a decrease in Clostridiales and
      increase in Proteobacteria. The tonsillar microbiome of older pigs resembled the
      previously described mature core tonsillar microbiome. This study demonstrates a
      temporal succession in the development of the pig tonsillar microbiome, and
      significant community shifts that correlate with disruption events.

PMID- 30283794
TI  - Algorithm for the multidisciplinary management of hemorrhage in EUS-guided
      drainage for pancreatic fluid collections.
AB  - Pancreatic fluid collections (PFCs), common sequelae of acute or chronic
      pancreatitis, are broadly classified as pancreatic pseudocysts or walled-off
      necrosis according to the revised Atlanta classification. Endoscopic ultrasound
      (EUS)-guided drainage is often considered a standard first-line therapy
      preferable to surgical or interventional radiology approaches for patients with
      symptomatic PFC. EUS-guided drainage is effective and successful; it has a
      technical success rate of 90%-100% and a clinical success rate of 85%-98%. Recent
      studies have shown a 5%-30% adverse events (AEs) rate for the procedure. The most
      common AEs include infection, hemorrhage, perforation and stent migration.
      Hemorrhage, a severe and sometimes deadly outcome, requires a well-organized and
      appropriate treatment strategy. However, few studies have reported the integrated
      management of hemorrhage during EUS-guided drainage of PFC. Establishing a
      practical therapeutic strategy is an essential and significant step in
      standardized management. The aim of this review is to describe the current
      situation of EUS-guided drainage of PFCs, including the etiology and treatment of
      procedure-related bleeding as well as current problems and future perspectives.
      We propose a novel and meaningful algorithm for systematically managing
      hemorrhage events. To our limited knowledge, a multidisciplinary algorithm for
      managing EUS-guided drainage for PFC-related bleeding has not been previously
      reported.

PMID- 30283793
TI  - A Predominant Clonal Thromboembolic Meningoencephalitis Group of Histophilus
      somni Assigned by Major Outer Membrane Protein Gene Sequencing and Pulsed-Field
      Gel Electrophoresis.
AB  - Histophilus somni, a member of the family Pasteurellaceae, causes a variety of
      diseases, including thromboembolic meningoencephalitis (TEME) and respiratory
      diseases, which result in considerable economic losses to the cattle and sheep
      industries. In this study, 132 chronologically diverse isolates from cattle in
      Japan and 68 isolates from other countries comprising 49 from cattle and 19 from
      sheep were characterized using major outer membrane protein (MOMP) gene sequence
      and pulsed-field gel electrophoresis (PFGE) analyses. The H. somni isolates
      formed nine MOMP genetic clades (clade Ia, Ib, and II-VIII) and 10 PFGE clusters
      (HS1-HS10). Except for two (1.0%), all isolates fell into one of the nine MOMP
      genetic clades, while 62 (31.0%) isolates belonged to no PFGE cluster. MOMP
      genetic clade Ia and PFGE cluster HS1 were the major groups, and all HS1 isolates
      possessed the clade Ia MOMP gene. Isolates from TEME cases were significantly
      associated with these major groups (chi-square test, p < 0.0001), as 88.2% of the
      TEME isolates belonged to MOMP genetic clade Ia and PFGE cluster HS1, which
      formed the most predominant clonal group. After an inactivated vaccine using an
      HS1 strain with the clade Ia MOMP gene was introduced in Japan in late 1989, the
      number of TEME cases and isolates assigned into the clonal group decreased
      simultaneously. However, the proportions of clade Ia and cluster HS1 isolates
      from TEME cases remained high after 1990. These results suggest a close
      association of TEME with PFGE cluster HS1 and MOMP genetic clade Ia, and imply
      the presence of factors or characteristics commonly possessed by those strains
      that contribute to the development of TEME.

PMID- 30283789
TI  - Genetic and Tissue Engineering Approaches to Modeling the Mechanics of Human
      Heart Failure for Drug Discovery.
AB  - Heart failure is the leading cause of death in the western world and as such,
      there is a great need for new therapies. Heart failure has a variable
      presentation in patients and a complex etiology; however, it is fundamentally a
      condition that affects the mechanics of cardiac contraction, preventing the heart
      from generating sufficient cardiac output under normal operating pressures. One
      of the major issues hindering the development of new therapies has been
      difficulties in developing appropriate in vitro model systems of human heart
      failure that recapitulate the essential changes in cardiac mechanics seen in the
      disease. Recent advances in stem cell technologies, genetic engineering, and
      tissue engineering have the potential to revolutionize our ability to model and
      study heart failure in vitro. Here, we review how these technologies are being
      applied to develop personalized models of heart failure and discover novel
      therapeutics.

PMID- 30283788
TI  - Changing Metabolism in Differentiating Cardiac Progenitor Cells-Can Stem Cells
      Become Metabolically Flexible Cardiomyocytes?
AB  - The heart is a metabolic omnivore and the adult heart selects the substrate best
      suited for each circumstance, with fatty acid oxidation preferred in order to
      fulfill the high energy demand of the contracting myocardium. The fetal heart
      exists in an hypoxic environment and obtains the bulk of its energy via
      glycolysis. After birth, the "fetal switch" to oxidative metabolism of glucose
      and fatty acids has been linked to the loss of the regenerative phenotype.
      Various stem cell types have been used in differentiation studies, but most are
      cultured in high glucose media. This does not change in the majority of cardiac
      differentiation protocols. Despite the fact that metabolic state affects marker
      expression and cellular function and activity, the substrate composition is
      currently being overlooked. In this review we discuss changes in cardiac
      metabolism during development, the various protocols used to differentiate
      progenitor cells to cardiomyocytes, what is known about stem cell metabolism and
      how consideration of metabolism can contribute toward maturation of stem cell
      derived cardiomyocytes.

PMID- 30283796
TI  - Research progress on signaling pathways in cirrhotic portal hypertension.
AB  - Portal hypertension (PHT) is an important consequence of liver cirrhosis, which
      can lead to complications that adversely affect a patient's quality of life and
      survival, such as upper gastrointestinal bleeding, ascites, and portosystemic
      encephalopathy. In recent years, advances in molecular biology have led to major
      discoveries in the pathological processes of PHT, including the signaling
      pathways that may be involved: PI3K-AKT-mTOR, RhoA/Rho-kinase, JAK2/STAT3, and
      farnesoid X receptor. However, the pathogenesis of PHT is complex and there are
      numerous pathways involved. Therefore, the targeting of signaling pathways for
      medical management is lagging. This article summarizes the progress that has been
      made in understanding the signaling pathways in PHT, and provides ideas for
      treatment of the disorder.

PMID- 30283795
TI  - Mystery behind labial and oral melanotic macules: Clinical, dermoscopic and
      pathological aspects of Laugier-Hunziker syndrome.
AB  - Labial and oral melanotic macules are commonly encountered in a broad range of
      conditions ranging from physiologic pigmentation to a sign of an underlying life
      threatening disease. Although Laugier-Hunziker syndrome (LHS) shares some
      features of labial and oral pigmentation with a variety of conditions, it is a
      benign and acquired condition, frequently associated with longitudinal
      melanonychia. Herein, the demographic, clinical, dermoscopic, and pathological
      aspects of LHS were reviewed comprehensively. The important differential
      diagnoses of mucocutaneous and nail pigmentation are provided. An accurate
      diagnosis is crucial to design a reasonable medical strategy, including
      management options, malignant transformation surveillance, and psychological
      support. It is important that clinicians conduct long-term follow-up and
      surveillance due to the potential risks of malignant transformation and local
      severe complications in some conditions.

PMID- 30283798
TI  - PNPLA3 rs139051 is associated with phospholipid metabolite profile and hepatic
      inflammation in nonalcoholic fatty liver disease.
AB  - AIM: To investigate the effect of PNPLA3 polymorphisms on serum lipidomics and
      pathological characteristics in nonalcoholic fatty liver disease (NAFLD).
      METHODS: Thirty-four biopsy-proven NAFLD patients from Northern, Central, and
      Southern China were subjected to stratification by genotyping their single
      nucleotide polymorphisms (SNPs) in PNPLA3. Ultra performance liquid
      chromatographytandem mass spectrometry was then employed to characterize the
      effects of PNPLA3 SNPs on serum lipidomics. In succession, correlation analysis
      revealed the association of PNPLA3-related lipid profile and hepatic pathological
      characteristics on a basis of steatosis, activity, and fibrosis assessment. The
      variant-based scoring of hepatocyte steatosis, ballooning, lobular inflammation,
      and liver fibrosis was finally performed so as to uncover the actions of
      lipidomics-affecting PNPLA3 SNPs in NAFLD-specific pathological alterations.
      RESULTS: PNPLA3 SNPs (rs139051, rs738408, rs738409, rs 2072906, rs2294918,
      rs2294919, and rs4823173) demonstrated extensive association with the serum
      lipidomics, especially phospholipid metabolites [lysophosphatidylcholine (LPC),
      lysophosphatidylcholine plasmalogen (LPCO), lysophosphatdylethanolamine (LPE),
      phosphatidylcholine (PC), choline plasmalogen (PCO), phosphatidylethanolamine
      (PE), ethanolamine plasmalogen (PEO)], of NAFLD patients. PNPLA3 rs139051 (A/A
      genotype) and rs2294918 (G/G genotype) dominated the up-regulatory effect on
      phospholipids of LPCs (LPC 17:0, LPC 18:0, LPC 20:0, LPC 20:1, LPC 20:2) and
      LPCOs (LPC O-16:1, LPC O-18:1). Moreover, subjects with high-level LPCs/LPCOs
      were predisposed to low-grade lobular inflammation of NAFLD (rho: -0.407 to 
      0.585, P < 0.05-0.001). The significant correlation of PNPLA3 rs139051 and
      inflammation grading [A/A vs A/G + G/G: 0.50 (0.00, 1.75) vs 1.50 (1.00, 2.00), P
      < 0.05] further demonstrated its pathological role based on the modulation of
      phospholipid metabolite profile. CONCLUSION: The A/A genotype at PNPLA3 rs139051
      exerts an up-regulatory effect on serum phospholipids of LPCs and LPCOs, which
      are associated with low-grade lobular inflammation of NAFLD.

PMID- 30283797
TI  - Gastrointestinal toxicity induced by microcystins.
AB  - Microcystins (MCs) are produced by certain bloom-forming cyanobacteria that can
      induce toxicity in various organs, including renal toxicity, reproductive
      toxicity, cardiotoxicity, and immunosuppressive effects. It has been a
      significant global environmental issue due to its harm to the aquatic environment
      and human health. Numerous investigators have demonstrated that MC exposure can
      induce a widespread epidemic of enterogastritis with symptoms similar to food
      poisoning in areas close to lakes. Both in vivo and in vitro studies have
      provided evidence of positive associations between MC exposure and
      gastrointestinal toxicity. The toxicity of MCs on the gastrointestinal tract is
      multidimensional. MCs can affect gastrointestinal barrier function and shift the
      structure of gut microbiota in different gut regions. Furthermore, MCs can
      inhibit the secretion of gastrointestinal digestive enzymes and the release of
      inflammatory cytokines, which affects the expression of immune-related genes in
      the intestine. The damage of the intestine is closely correlated to MC exposure
      because the intestine is the main site for the digestion and absorption of
      nutrients. The damage to the gastrointestinal tract due to MCs was summarized
      from different aspects, which can be used as a foundation for further exploration
      of molecular damage mechanisms.

PMID- 30283799
TI  - Recurrent carpal tunnel syndrome: Evaluation and treatment of the possible
      causes.
AB  - AIM: To investigate the causes of the recurrent carpal tunnel syndrome (CTS) and
      implemented surgical interventions. METHODS: Four hundred and eighty-seven
      patients, who were diagnosed with CTS and underwent surgical intervention between
      October 2016 and September 2007, were evaluated in this retrospective study. The
      age, gender, physical evaluation findings, electrophysiological examination
      reports and implemented surgical treatment methods were analyzed. RESULTS: Thirty
      nine of the cases were operated due to recurrent CTS. Further examination of the
      patients with recurrent CTS revealed that ten cases had diabetic polyneuropathy,
      three cases had hypothyroidism, two cases had rheumatoid arthritis and one case
      had systemic amyloidosis. Postoperative electromyography confirmed the neuropathy
      was due to systemic diseases. The remaining 23 patients with recurrent CTS did
      not have any systemic disease and all of them had applied previously to another
      health center. CONCLUSION: We concluded that the recurrence rates in CTS might be
      decreased with exploration and incision of the entire transverse ligament. Damage
      to the motor and sensory branches of the median nerve could be avoided with an
      incision on the ulnar side.

PMID- 30283800
TI  - Adjuvant chemotherapy with S-1 plus oxaliplatin improves survival of patients
      with gastric cancer after D2 gastrectomy: A multicenter propensity score-matched
      study.
AB  - AIM: To investigate the safety and efficacy of S-1 plus oxaliplatin (SOX) as an
      adjuvant chemotherapy regimen in gastric cancer (GC) after D2 dissection.
      METHODS: GC Patients who underwent D2 gastrectomy from September 2009 to December
      2011 in four Chinese institutions were enrolled. Patients with stage IB-IIIC GC,
      who received adjuvant SOX treatment were matched by propensity scores with those
      who underwent surgery alone and those who conducted capecitabine plus oxaliplatin
      (XELOX) regimen. Disease-free survival (DFS) and overall survival (OS) were
      compared among the groups. In addition, adverse events in SOX patients were
      analyzed. RESULTS: Of 1944 GC patients who underwent D2 dissection, 867 were
      included for analysis. One hundred and seventeen patients treated with SOX were
      matched to 234 patients who conducted surgery alone. Fifty-seven patients treated
      with SOX were matched to 57 patients who received XELOX. The estimated five-year
      DFS was 57.5% in the adjuvant SOX group which was higher than that (44.6%) in the
      surgery alone group (P = 0.001); and the estimated five-year OS was 68.3% which
      was higher than that (45.8%) of surgery alone group (P < 0.001). Survival benefit
      was also revealed in stage III and > 60 years old subgroups (P < 0.001 and P =
      0.015, respectively). Compared with XELOX regimen, SOX showed no significant
      difference in DFS (P = 0.340) and OS (P = 0.361). The most common >= 3 grade
      adverse events of SOX regimen were neutropenia (22.6%), leukopenia (8.9%) and
      thrombocytopenia (5.6%). CONCLUSION: Compared with surgery alone, SOX regimen
      significantly improves the long-term survival and has acceptable toxicity in
      patients with stage IB-IIIC GC after D2 dissection. It may be a novel adjuvant
      chemotherapy regimen in GC patients.

PMID- 30283802
TI  - Unusual complication in patient with Gardner's syndrome: Coexistence of triple
      gastrointestinal perforation and lower gastrointestinal bleeding: A case report
      and review of literature.
AB  - Gardner's syndrome (GS) is a rare syndrome with autosomal dominant inheritance,
      which is characterized by multiple intestinal polyps, dental anomalies, desmoid
      tumors, and soft tissue tumors. All gastrointestinal symptoms seen in GS are
      associated with the underlying familial adenomatosis polyposis and abdominal
      desmoid tumors, with the most common symptoms being anemia, lower
      gastrointestinal bleeding, abdominal pain, diarrhea, obstruction, and mucous
      defecation. To our best knowledge, no case of GS that has presented with
      gastrointestinal perforation and bleeding has ever been reported in the English
      language medical literature. A 37-year-old male who had been diagnosed with GS
      five years earlier was referred to our clinic for lower gastrointestinal
      bleeding. Despite the absence of a bleeding focus on conventional angiography,
      the patient was operated on with laparotomy, due to the persistence of both signs
      and symptoms of mild peritonitis. On the laparotomy, the patient was noted to
      have areas of perforation in the duodenum, splenic flexura, and mid-rectum. The
      third and fourth part of the duodenum, the proximal 15 cm segment of the jejunum,
      a 10 cm segment of the terminal ileum, the whole colon, and the upper and middle
      rectum were resected, and duodeno-jejunal side-to-side anastomosis and terminal
      ileostomy were performed. The histopathological analysis of the large mass
      measuring 30 cm * 20 cm was reported as a desmoid tumor. The pathological
      examination of the tumor foci detected in the colonic specimen revealed poorly
      differentiated adenosquamous carcinoma.

PMID- 30283801
TI  - Rectal perforation by inadvertent ingestion of a blister pack: A case report and
      review of literature.
AB  - The accidental ingestion of a foreign body (FB) is a relatively common condition.
      In the present study, we report a peculiar case of rectal perforation, the first
      to our knowledge, caused by the inadvertent ingestion of a blister pill pack. The
      aim of this report is to illustrate the difficulties of the case from a
      diagnostic and therapeutic viewpoint as well as its unusual presentation. A 75
      year-old woman, mentally impaired, arrived at our emergency department in
      critical condition. The computed tomography scan revealed a substantial
      abdominopelvic peritoneal effusion and free perigastric air. The patient was
      therefore submitted to an urgent exploratory laparotomy; a 2-cm long, full
      thickness lesion was identified in the anterior distal part of the
      intraperitoneal rectum. Hence, we performed a Hartmann's procedure. Because of
      her critical condition, the patient was eventually transferred to the Intensive
      Care Unit, where she died after 10 d, showing no surgical complication. The
      ingestion of FBs is usually treated with observation or endoscopic removal. Less
      than 1% of FBs are likely to cause an intestinal perforation. The intestinal
      perforation resulting from the unintentional ingestion of an FB is often a
      difficult challenge when it comes to treatment, due to its late diagnosis and the
      patients' deteriorated clinical condition.

PMID- 30283803
TI  - Laparoscopic repair via the transabdominal preperitoneal procedure for bilateral
      lumbar hernia: Three cases report and review of literature.
AB  - A lumbar hernia is a rare entity, and a bilateral lumbar hernia is much rarer.
      From May 2015 to October 2017, we treated only three patients with bilateral
      lumbar hernias. One patient came to the hospital presenting with right-sided
      abdominal pain, and the other two patients presented with bilateral lumbar
      masses. The previous bilateral lumbar hernia reported in the literature was
      repaired by open surgery. The laparoscopic approach via the transabdominal
      preperitoneal (TAPP) procedure with the self-gripping Parietex ProGripTM mesh was
      performed at our center. The laparoscopic repair was conducted by a skilled
      hernia surgeon, and was successfully performed in the three patients. The
      patients resumed a semi-liquid diet and had no activity restriction after six
      hours following the operation. No antibiotics were used after the surgery. The
      operative times of the three patients were 120 min, 85 min, and 130 min. The
      blood loss volumes of the three patients were 20 mL, 5 mL, and 5 mL. The visual
      analogue scale pain scores of the three patients were 1, 2, and 2 on
      postoperative day 1, and were 1, 2, and 1 on postoperative day 3. No
      perioperative complications, such as bulge, wound infection and hematoma,
      occurred after the surgery. All of the patients were discharged on the third day
      after the operation. There was no chronic pain and no hernia recurrence during
      the follow-up. This study showed that the laparoscopic TAPP approach with the
      self-gripping mesh is safe and feasible, and can be considered an alternative
      method for the treatment of bilateral lumbar hernias.

PMID- 30283804
TI  - Multiple Symmetric Lipomatosis (Madelung Disease) in a Large Canadian Family With
      the Mitochondrial MTTK c.8344A>G Variant.
AB  - Background. Multiple symmetric lipomatosis (MSL), also known as Madelung disease,
      is a rare adult-onset disorder characterized by benign lipomatosis usually
      localized to the nuchal and upper thoracic region. A subset of these patients has
      germline variants in mitochondrial DNA. Methods. Three siblings of Northern
      European descent with MSL were assessed initially and provided whole blood for
      DNA analysis. Family history revealed several additional affected siblings who
      were dispersed across Canada. Targeted histories were obtained from 6 additional
      affected family members by telephone interviews using a standardized
      questionnaire, and genomic DNA was obtained from saliva. Sequencing of
      mitochondrial DNA was performed. Genetic analysis. Eight affected individuals who
      were studied each had the MTTK gene c.8344A>G variant. None of the affected
      individuals had epilepsy, ataxia, or myopathy. Conclusion. In this extended
      Canadian family, the rare MTTK c.8344A>G variant was linked with Madelung disease
      in multiple family members. Knowing the likely basis of MSL in this family may
      help with diagnosis, genetic counseling, monitoring for associated phenotypes,
      and potential future targeted interventions.

PMID- 30283805
TI  - A Good Case of Recurrent Pneumonia.
AB  - Bordetella bronchiseptica infection is a common cause of pneumonia in animals but
      rarely causes disease in humans. Additionally, coinfection with Pneumocystis
      jirovecii is very uncommon and is occasionally seen in patients with acquired
      immunodeficiency syndrome (AIDS). We report a case of a 61-year-old HIV-negative
      man, who presented with hypoxic respiratory failure 2 days after completion of
      systemic intravenous antibiotic treatment for B bronchiseptica. His past medical
      history was significant for a benign thymoma. The patient was found to be
      coinfected with B bronchiseptica and P jirovecii. Laboratory results showed
      panhypogammaglobulinemia and low absolute B- and CD4 T-cells. Therefore, the
      patient was diagnosed with Good's syndrome. However, despite treatment with
      intravenous antibiotics and intravenous immunoglobulin, the patient continued to
      deteriorate and expired. This patient demonstrates the importance of recognizing
      this rare immunodeficiency early in order to improve morbidity and mortality.
      Furthermore, this case highlights the importance of early immunoglobulin
      screening in the presence of asymptomatic thymoma.

PMID- 30283806
TI  - Atrial Fibrillation in a Patient With an Accessory Pathway.
AB  - A 24-year-old man with history of unspecified arrhythmia presented with
      palpitations and chest pain. Initial electrocardiogram (ECG) revealed irregular
      tachycardia with varying QRS width: 150 to 200 beats per minute for narrow
      complexes and 300 beats per minute for wide complexes. Following cardioversion,
      ECG revealed sinus tachycardia with a preexcitation pattern of positive delta
      waves in the anterolateral leads and negative delta waves in inferior leads. The
      patient remained in sinus rhythm and underwent successful ablation of a right
      posteroseptal accessory pathway. Subsequent ECG showed upright T waves in the
      leads I, aVL, and V2-6, large inverted T waves in leads III and aVF, and no delta
      waves. This case serves as an important reminder that atrial fibrillation (AF) in
      the presence of an accessory pathway may present with confounding ECG features,
      potentially leading to incorrect diagnoses and treatments that may be life
      threatening. Despite 10% to 30% prevalence of AF in the presence of an accessory
      pathway and the relative awareness of Wolff-Parkinson-White syndrome among
      general internal medicine providers, the clinical recognition of Wolff-Parkinson
      White syndrome may be hindered in the presence of preexcited AF.

PMID- 30283808
TI  - Chilaiditi Syndrome Complicated by Cecal Perforation in the Setting of
      Scleroderma.
AB  - Chilaiditi syndrome is a very rare disorder characterized by abdominal pain due
      to the entrapment of the colon between the liver and the diaphragm. However, it
      is rare to have bowel perforation as a complication of this syndrome with only 2
      cases reported to date. In this article, we present the case of a 56-year-old
      woman with medical history of scleroderma who presents with abdominal pain and
      was found to have colonic perforation from Chilaiditi syndrome. She was also
      incidentally found to have cecal adenocarcinoma. Sometimes abdominal pain in
      patients with Chilaiditi syndrome may be more than benign and calls for increased
      attention from clinicians regarding this.

PMID- 30283807
TI  - Embolizing Massive Right Atrial Thrombus in a HIV-Infected Patient.
AB  - The risk of thromboembolism is increased when associated with the human
      immunodeficiency viral (HIV) infection. Various factors are involved in promoting
      thrombosis, and the presence of a patent foramen ovale augments the potential for
      a paradoxical embolism. We describe the case of a 56-year-old man receiving
      antiretroviral therapy with features of right heart failure and pulmonary
      embolism. Due to the high incidence of life-threatening thromboembolism in the
      HIV-infected group, the need for long-term anticoagulation has to be evaluated.

PMID- 30283810
TI  - In vitro Enzymatic Assays of Histone Decrotonylation on Recombinant Histones.
AB  - Class I histone deacetylases (HDACs) are efficient histone decrotonylases,
      broadening the enzymatic spectrum of these important (epi-)genome regulators and
      drug targets. Here, we describe an in vitro approach to assaying class I HDACs
      with different acyl-histone substrates, including crotonylated histones and
      expand this to examine the effect of inhibitors and estimate kinetic constants.

PMID- 30283809
TI  - The Relative Biological Effect of Spread-Out Bragg Peak Protons in Sensitive and
      Resistant Tumor Cells.
AB  - Purpose: Variations in the radiosensitivity of tumor cells within and between
      tumors impact tumor response to radiation, including the dose required to achieve
      permanent local tumor control. The increased expression of DNA-PKcs, a key
      component of a major DNA damage repair pathway in tumors treated by radiation,
      suggests that DNA-PKcs-dependent repair is likely a cause of tumor cell
      radioresistance. This study evaluates the relative biological effect of spread
      out Bragg-peak protons in DNA-PKcs-deficient cells and the same cells transfected
      with a functional DNA-PKcs gene. Materials and Methods: A cloned radiation
      sensitive DNA-PKcs-deficient tumor line and its DNA-PKcs-transfected resistant
      counterpart were used in this study. The presence of functional DNA-PKcs was
      evaluated by DNA-PKcs autophosphorylation. Cells to be proton irradiated or x
      irradiated were obtained from the same single cell suspension and dilution series
      to maximize precision. Cells were concurrently exposed to 6-MV x-rays or mid 137
      MeV spread-out Bragg peak protons and cultured for colony formation. Results: The
      surviving fraction data were well fit by the linear-quadratic model for each of 8
      survival curves. The results suggest that the relative biological effectiveness
      of mid spread-out Bragg peak protons is approximately 6% higher in DNA-PKcs
      mediated resistant tumor cells than in their DNA-PKcs-deficient and radiation
      sensitive counterpart. Conclusion: DNA-PKcs-dependent repair of radiation damage
      is less capable of repairing mid spread-out Bragg peak proton lesions than photon
      induced lesions, suggesting protons may be more efficient at sterilizing DNA-PKcs
      expressing cells that are enriched in tumors treated by conventional fractionated
      dose x-irradiation.

PMID- 30283811
TI  - Pentylenetetrazole (PTZ)-induced Convulsion Assay to Determine GABAergic Defects
      in Caenorhabditis elegans.
AB  - Pentylenetetrazole (PTZ) is a GABAA receptor antagonist and is used to monitor
      presynaptic defects in the release of the inhibitory neurotransmitter GABA. PTZ
      is a competitive inhibitor of GABA, and prevents binding of GABA on the GABAA
      receptors present on the surface of muscle. In the absence of GABA binding, the
      excitatory to inhibitory signal ratio increases resulting in a convulsive
      phenotype. This assay provides a fast and reliable method to detect presynaptic
      defects in GABAergic synaptic transmission. The assay is based on correlating the
      extent of convulsions with the degree of presynaptic GABA release defects.

PMID- 30283812
TI  - Mononuclear cell transcriptome changes associated with dimethyl fumarate in MS.
AB  - Objective: To identify short-term changes in gene expression in peripheral blood
      mononuclear cells (PBMCs) associated with treatment response to dimethyl fumarate
      (DMF, Tecfidera) in patients with relapsing-remitting MS (RRMS). Methods: Blood
      samples were collected from 24 patients with RRMS (median Expanded Disability
      Status Scale score, 2.0; range 1-7) at baseline, 6 weeks, and 15 months after the
      initiation of treatment with DMF (BG-12; Tecfidera). Seven healthy controls were
      also recruited, and blood samples were collected over the same time intervals.
      PBMCs were extracted from blood samples and sequenced using next-generation RNA
      sequencing. Treatment responders were defined using the composite outcome measure
      "no evidence of disease activity" (NEDA-4). Time-course and cross-sectional
      differential expression analyses were performed to identify transcriptomic
      markers of treatment response. Results: Treatment responders (NEDA-4 positive,
      8/24) over the 15-month period had 478 differentially expressed genes (DEGs) 6
      weeks after the start of treatment. These were enriched for nuclear factor
      (erythroid-derived 2)-like 2 (Nrf2) and inhibition of nuclear factor kappaB
      (NFkappaB) pathway transcripts. For patients who showed signs of disease
      activity, there were no DEGs at 6 weeks relative to their (untreated) baseline.
      Contrasting transcriptomes expressed at 6 weeks with those at 15 months of
      treatment, 0 and 1,264 DEGs were found in the responder and nonresponder groups,
      respectively. Transcripts in the nonresponder group (NEDA-4 negative, 18/24) were
      enriched for T-cell signaling genes. Conclusion: Short-term PBMC transcriptome
      changes reflecting activation of the Nrf2 and inhibition of NFkappaB pathways
      distinguish patients who subsequently show a medium-term treatment response with
      DMF. Relative stabilization of gene expression patterns may accompany treatment
      associated suppression of disease activity.

PMID- 30283814
TI  - Changes in Functional Brain Connectivity Highlight the Importance of a Baseline
      Measurement and Multiple Imaging Sessions for Cocaine Abstinence Studies.
AB  - Highlighted Research Paper: Functional Connectivity of Chronic Cocaine Use
      Reveals Progressive Neuroadaptations in Neocortical, Striatal, and Limbic
      Networks by, Caitlin A. Orsini, Luis M. Colon-Perez, Sara C. Heshmati, Barry
      Setlow, and Marcelo Febo.

PMID- 30283815
TI  - Genetic landscape of pediatric movement disorders and management implications.
AB  - Objective: To identify underlying genetic causes in patients with pediatric
      movement disorders by genetic investigations. Methods: All patients with a
      movement disorder seen in a single Pediatric Genetic Movement Disorder Clinic
      were included in this retrospective cohort study. We reviewed electronic patient
      charts for clinical, neuroimaging, biochemical, and molecular genetic features.
      DNA samples were used for targeted direct sequencing, targeted next-generation
      sequencing, or whole exome sequencing. Results: There were 51 patients in the
      Pediatric Genetic Movement Disorder Clinic. Twenty-five patients had dystonia, 27
      patients had ataxia, 7 patients had chorea-athetosis, 8 patients had tremor, and
      7 patients had hyperkinetic movements. A genetic diagnosis was confirmed in 26
      patients, including in 20 patients with ataxia and 6 patients with dystonia.
      Targeted next-generation sequencing panels confirmed a genetic diagnosis in 9
      patients, and whole exome sequencing identified a genetic diagnosis in 14
      patients. Conclusions: We report a genetic diagnosis in 26 (51%) patients with
      pediatric movement disorders seen in a single Pediatric Genetic Movement Disorder
      Clinic. A genetic diagnosis provided either disease-specific treatment or
      effected management in 10 patients with a genetic diagnosis, highlighting the
      importance of early and specific diagnosis.

PMID- 30283813
TI  - Connectome of the Suprachiasmatic Nucleus: New Evidence of the Core-Shell
      Relationship.
AB  - A brain clock, constituted of ~20,000 peptidergically heterogeneous neurons, is
      located in the hypothalamic suprachiasmatic nucleus (SCN). While many peptidergic
      cell types have been identified, little is known about the connections among
      these neurons in mice. We first sought to identify contacts among major
      peptidergic cell types in the SCN using triple-label fluorescent
      immunocytochemistry (ICC). To this end, contacts among vasoactive intestinal
      polypeptide (VIP), gastrin-releasing peptide (GRP), and calretinin (CALR) cells
      of the core, and arginine vasopressin (AVP) and met-enkephalin (ENK) cells of the
      shell were analyzed. Some core-to-shell and shell-to-core communications are
      specialized. We found that in wild-type (WT) mice, AVP fibers make extremely
      sparse contacts onto VIP neurons but contacts in the reverse direction are
      numerous. In contrast, AVP fibers make more contacts onto GRP neurons than
      conversely. For the other cell types tested, largely reciprocal connections are
      made. These results point to peptidergic cell type-specific communications
      between core and shell SCN neurons. To further understand the impact of VIP-to
      AVP communication, we next explored the SCN in VIP-deficient mice (VIP-KO). In
      these animals, AVP expression is markedly reduced in the SCN, but it is not
      altered in the paraventricular nucleus (PVN) and supraoptic nucleus (SON).
      Surprisingly, in VIP-KO mice, the number of AVP appositions onto other
      peptidergic cell types is not different from controls. Colchicine administration,
      which blocks AVP transport, restored the numbers of AVP neurons in VIP-KO to that
      of WT littermates. The results indicate that VIP has an important role in
      modulating AVP expression levels in the SCN in this mouse.

PMID- 30283817
TI  - Homozygosity for SCN4A Arg1142Gln causes congenital myopathy with variable
      disease expression.

PMID- 30283816
TI  - Protein network analysis reveals selectively vulnerable regions and biological
      processes in FTD.
AB  - Objective: The neuroanatomical profile of behavioral variant frontotemporal
      dementia (bvFTD) suggests a common biological etiology of disease despite
      disparate pathologic causes; we investigated the genetic underpinnings of this
      selective regional vulnerability to identify new risk factors for bvFTD. Methods:
      We used recently developed analytical techniques designed to address the
      limitations of genome-wide association studies to generate a protein interaction
      network of 63 bvFTD risk genes. We characterized this network using gene
      expression data from healthy and diseased human brain tissue, evaluating regional
      network expression patterns across the lifespan as well as the cell types and
      biological processes most affected in bvFTD. Results: We found that bvFTD network
      genes show enriched expression across the human lifespan in vulnerable neuronal
      populations, are implicated in cell signaling, cell cycle, immune function, and
      development, and are differentially expressed in pathologically confirmed
      frontotemporal lobar degeneration cases. Five of the genes highlighted by our
      differential expression analyses, BAIAP2, ERBB3, POU2F2, SMARCA2, and CDC37,
      appear to be novel bvFTD risk loci. Conclusions: Our findings suggest that the
      cumulative burden of common genetic variation in an interacting protein network
      expressed in specific brain regions across the lifespan may influence
      susceptibility to bvFTD.

PMID- 30283818
TI  - Deoxyguanosine kinase mutation producing juvenile-onset mitochondrial myopathy.

PMID- 30283819
TI  - CADASIL affecting a black African man.

PMID- 30283820
TI  - DRESS after IV phenytoin associated with cytochrome P450 CYP2C9*3 homozygosity.

PMID- 30283821
TI  - AP4S1 splice-site mutation in a case of spastic paraplegia type 52 with
      polymicrogyria.

PMID- 30283822
TI  - Regulatory Status of Cannabidiol in the United States: A Perspective.
AB  - Cannabidiol (CBD) is 1 of > 100 cannabinoids found in Cannabis sativa L.
      (Cannabis spp. or Cannabis). Despite its complex and rapidly evolving regulatory
      status in the United States, projected retail sales of CBD products-hemp,
      Cannabis and pharmaceutical-are as high as $1.9 billion by 2020. CBD products can
      currently be purchased online, over the counter, and at Cannabis-specific
      dispensaries throughout most parts of the country, despite the fact that CBD is
      presently deemed a Schedule I controlled substance by the U.S. Drug Enforcement
      Administration and renounced as a dietary supplement ingredient by the U.S. Food
      and Drug Administration (FDA). These products are largely unregulated, and are
      being used predominantly to treat specific medical conditions. Recent FDA
      approval of Epidiolex (CBD) as a treatment for certain pediatric seizure
      disorders will prompt scheduling of CBD and likely alter FDA enforcement of the
      Federal Food, Drug, and Cosmetic Act (FD&C), which to date has mostly been in the
      form of warning letters. Persuasive legal arguments contend that CBD's legal
      status is based on its source. According to these arguments, there are three
      legal sources. CBD-derived from: (1) parts of the Cannabis plant that do not meet
      the definition of cannabis in the Controlled Substances Act (CSA); (2) imported
      "non-psychoactive hemp"; and (3) "Industrial hemp" cultivated as part of a state
      pilot program per the 2014 Farm Act. Although CBD's lawful status with respect to
      the CSA appears to be expanding, its future regulatory status with respect to the
      FD&C Act is difficult to predict.

PMID- 30283823
TI  - Fecal Host Transcriptomics for Non-Invasive Human Mucosal Immune Profiling: Proof
      of Concept in Clostridium Difficile Infection.
AB  - Background: Host factors play an important role in pathogenesis and disease
      outcome in Clostridium difficile infection (CDI), and characterization of these
      responses could uncover potential host biomarkers to complement existing microbe
      based diagnostics. Methods: We extracted RNA from fecal samples of patients with
      CDI and profiled human mRNA using amplicon-based next-generation sequencing
      (NGS). We compared the fecal host mRNA transcript expression profiles of patients
      with CDI to controls with non-CDI diarrhea. Results: We found that the ratio of
      human actin gamma 1 (ACTG1) to 16S ribosomal RNA (rRNA) was highly correlated
      with NGS quality as measured by percentage of reads on target. Patients with CDI
      could be differentiated from those with non-CDI diarrhea based on their fecal
      mRNA expression profiles using principal component analysis. Among the most
      differentially expressed genes were ones related to immune response (IL23A, IL34)
      and actin-cytoskeleton function (TNNT1, MYL4, SMTN, MYBPC3, all adjusted P-values
      < 1 * 10-3). Conclusions: In this proof-of-concept study, we used host fecal
      transcriptomics for non-invasive profiling of the mucosal immune response in CDI.
      We identified differentially expressed genes with biological plausibility based
      on animal and cell culture models. This demonstrates the potential of fecal
      transcriptomics to uncover host-based biomarkers for enteric infections.

PMID- 30283824
TI  - Cystic Fibrosis Mice Develop Spontaneous Chronic Bordetella Airway Infections.
AB  - Chronic pulmonary disease and infection is the primary cause of morbidity and
      mortality in people with cystic fibrosis (CF). Though Pseudomonas aeruginosa, is
      most commonly found in the airways of individuals with CF, there is increasing
      appreciation for the diversity of the CF microbiome, including other taxa such as
      Bordetella. Here we describe the identification and impact of Bordetella
      pseudohinzii infection in CF mice, which previously have not been thought to
      develop spontaneous airway infections. We determined that CF mice are more
      susceptible to the B. pseudohinzii infections, and less able to resolve the
      infection than non-CF mice. Moreover, in both CF and non-CF mice, B. pseudohinzii
      infections lead to markedly reduced respiratory rates and a CF-specific immune
      response. These results establish the CF mouse model as an important tool for the
      study of CF-relevant infection and highlight the potential contribution of
      Bordetella to CF clinical pathology.

PMID- 30283825
TI  - A Case of Familial Male-Limited Precocious Puberty in a Child With Klinefelter
      Syndrome.
AB  - Familial male-limited precocious puberty (FMPP) is an autosomal dominant, male
      limited disorder that causes peripheral precocious puberty in boys. Klinefelter
      syndrome (47, XXY) is the most common chromosomal aberration in males with
      associated infertility, hypogonadism, and learning disability. We report here a
      case of Klinefelter syndrome in a patient with FMPP. A 6-year-old boy was
      referred to our pediatric endocrinology department for accelerated linear growth
      and premature pubic hair development. He was diagnosed with FMPP based on
      clinical, laboratory, and genetic sequencing. Increased levels of gonadotropins
      prompted further investigation, leading to a subsequent diagnosis of Klinefelter
      syndrome through karyotype analysis. This case illustrates that patients with
      FMPP and elevated gonadotropins should encourage further investigation by
      physicians. We recommend the use of karyotype analysis in such patients who are
      not receiving aromatase inhibitor therapy. We hypothesize that his mutation or
      pretreatment with aromatase inhibitors may have a protective effect on
      testosterone production and sperm viability.

PMID- 30283826
TI  - Prevalence of Somatic KCNJ5 Mutations in Thai Patients With Aldosterone-Producing
      Adrenal Adenomas.
AB  - Somatic KCNJ5 mutations result in excess aldosterone production and are reported
      to be more common in Asia than elsewhere. To assess the prevalence of somatic
      KCNJ5 mutations in Thai patients with aldosterone-producing adrenal adenomas
      (APAs) in a single tertiary center, we analyzed the paraffin-embedded tissue of
      KCNJ5 mutations from 96 patients with sporadic APAs who underwent unilateral
      laparoscopic adrenalectomy at our center during 2007 to 2016. We also assessed
      the clinical characteristics, treatment outcomes, and biochemistry and histologic
      differences among patients with and without somatic KCNJ5 mutations. Of the 96
      patients with APA, 67 (70%) had somatic mutations of the KCNJ5 gene: 39 patients
      with p.G151R, 26 patients with p.L168R, one patient with p.T158A, and one patient
      with p.W126R. All patients presented with hypertension. Hypokalemia was
      documented in 98% of patients. The hypertension cure rate at 1 year after surgery
      was 35%. Patients with somatic KCNJ5 mutations required more potassium
      supplementation and had adrenal histology compatible with zona fasciculata-like
      cells compared with patients without the mutations (all P < 0.05). There were no
      significant differences in preoperative plasma aldosterone concentration (PAC),
      plasma renin activity, aldosterone/renin ratio, potassium level, treatment of
      hypertension, tumor size, and hypertension cure rate among patients in the KCNJ5
      mutant and nonmutant groups. In a multivariate analysis, a higher PAC was
      associated with the presence of somatic KCNJ5 mutations. In summary, the
      prevalence of somatic KCNJ5 mutations in patients with sporadic APAs in Thailand,
      an Asian country with residents of different ethnic backgrounds, is comparable to
      previous reports in Asia.

PMID- 30283828
TI  - A Space to Promote Intentional Thoughtful Action.

PMID- 30283827
TI  - Significant Association of Aldosterone and Liver Fat Among HIV-Infected
      Individuals With Metabolic Dysregulation.
AB  - Objective: Fatty liver disease is increased among individuals with HIV. We sought
      to explore how aldosterone, a key hormone linked to insulin resistance and
      inflammation, relates to liver fat in the large population of individuals with
      HIV and metabolic abnormalities. Methods: Forty-six individuals with HIV and
      increased waist circumference and dysglycemia were assessed for liver fat using
      proton magnetic resonance spectroscopy. Serum aldosterone level was obtained
      following strictly controlled posture conditions and a standardized sodium diet
      and was related to liver fat. Results: Among the entire group [median
      (interquartile range) liver fat: 5% (3%, 12%) and homeostatic model assessment of
      insulin resistance: 1.74 (1.21, 2.83)], serum aldosterone significantly
      correlated with liver fat (r = 0.31; P = 0.049). Liver fat level was
      significantly higher in those with aldosterone above vs below the median [8% (3%,
      20%) vs 4% (2%, 10%); P = 0.02]. In the presence of metabolic syndrome,
      individuals with aldosterone levels above vs below the median had markedly
      elevated liver fat values [14% (9%, 23%) vs 5% (3%, 12%); P = 0.005] and
      increased presence of fatty liver disease (FLD; 92% vs 50%; P = 0.02).
      Controlling for metabolic syndrome, hepatitis C virus, and alcohol use,
      aldosterone was a significant and independent predictor of liver fat (beta
      estimate: 0.6038, P = 0.01; overall model r 2 = 0.41, P = 0.0005) and FLD (OR:
      1.38, P = 0.02; overall model r 2 = 0.28, P = 0.002). Conclusion: These data
      highlight a robust association between aldosterone and liver fat among
      individuals with HIV and metabolic dysregulation. Increased aldosterone may be a
      risk factor for liver fat accumulation among the population with HIV.

PMID- 30283829
TI  - Text Messaging in the Patient-Centered Medical Home to Improve Glucose Control
      and Retinopathy Screening.
AB  - Purpose: To evaluate the effectiveness of a text messaging program (TMP) to
      improve glucose control, retinopathy screening (RS) rates, and self-care
      behaviors in patients with uncontrolled type 2 diabetes. Methods: A single-group
      design with a quasi-systematic random sample (n=20) received
      educational/exhortational text messages on their cellular phones for 3 months.
      Subjects, 12 of whom identified as a minority ethnicity, were mostly male, aged
      27-73 years. Results: Glucose control and RS rates improved significantly.
      Subjects (>70%) reported changes in self-care behaviors. Conclusion: Leveraging
      ubiquitous technology, a TMP for patients with limited access to healthcare
      education, holds promise.

PMID- 30283830
TI  - Partnering on the PRAISE Program: Putting Health Equity into Practice.
AB  - Purpose: The purpose of Preventive Health Education Resulting in Action Inspiring
      Success for Everyone (PRAISE) was to develop a community-driven program to
      encourage and support churches in sustainable health promotion and assessment
      efforts to improve African Americans' health knowledge and behaviors in
      Asheville, North Carolina. Methods: The PRAISE program provided technical support
      toward gaining recognition and an award for health promotion activities to 10
      churches in year 1 and 5 additional churches in year 2. The Results-Based
      Accountability(c) (RBA) framework involved documentation of church health
      promotion activities and surveys of a convenience sample of congregants at nine
      churches before (presurvey, n=270) and after (postsurvey, n=241) the
      intervention. Differences in frequency of conduct of and participation in church
      health promotion activities and in congregant health knowledge and behaviors were
      assessed in 2015 and 2016. Results: Fourteen of the churches engaged in at least
      one health promotion activity and more than half offered healthier foods at
      gatherings, offered exercise opportunities, and held at least three health
      education activities. Seventy-two percent of congregants reported participating
      in at least one church health activity at postsurvey compared with 58% at
      presurvey. The proportion of congregants who had personal health knowledge and
      the proportion that rated their health as good or better were higher at
      postsurvey. Conclusion: Building on years of trust and collaboration among
      churches, local community organizations, and an academic partner, PRAISE in its
      first 2 years suggests that a community-driven approach can support health
      promotion and healthy behaviors, advancing health equity efforts.

PMID- 30283832
TI  - From Principles to Practice: One Local Health Department's Journey Toward Health
      Equity.
AB  - Few dispute that social determinants such as economics, education, and the
      environment are the true drivers of health. In fact, the recent "Public Health
      3.0" publication is a national call to action for public health to focus
      upstream. Where there is less clarity is how to redesign public health practice
      to address social determinants. As an example of how local health departments can
      heed this national call, Harris County Public Health describes its movement from
      health equity principles to practice, which included reframing an understanding
      of health inequities and applying a multitiered infrastructure of policy and
      procedures for "retrofitting" practice.

PMID- 30283831
TI  - Measuring Medical Students' Preparedness and Skills to Provide Cross-Cultural
      Care.
AB  - Purpose: Cross-cultural education is an integral and required part of
      undergraduate medical curricula. However, the teaching of cross-cultural care
      varies widely and methods of evaluation are lacking. We sought to better
      understand medical students' perspectives on their own cultural competency across
      the 4-year curriculum using a validated survey instrument. Methods:We conducted
      an annual Internet-based survey at Harvard Medical School with students in all 4
      years of training, for four consecutive years. We used a tool previously
      validated with residents and slightly modified it for medical students, assessing
      their (1) preparedness, (2) skillfulness, and (3) perspectives on the educational
      curriculum and learning climate. Results: Of 2592 possible survey responses, we
      received 1561 (60% response rate). Fourth-year students had significantly higher
      scores than first-year students (p<0.001) for all but one preparedness item
      (caring for transgender patients) and all but one skillfulness item (identifying
      ability to read/write English). Less than 50% of students felt adequately
      prepared/skilled by their fourth year on 8 of 11 preparedness items and 5 of 10
      skillfulness items. Lack of practical experience caring for diverse patients was
      the most frequently cited challenge. Conclusions: While students reported that
      preparedness and skillfulness to care for culturally diverse patients seem to
      increase with training, fourth-year students still felt inadequately prepared and
      skilled in many important aspects of cross-cultural care. Medical schools can use
      this tool with students to self-assess cultural competency and to help guide
      enhancements to their curricula focusing on cross-cultural care.

PMID- 30283833
TI  - Perspectives on Barriers to Eating Healthy Among Food Pantry Clients.
AB  - Objective: To explore perspectives on barriers of eating healthy among food
      pantry clients. Methods: Food pantry clients participated in focus
      groups/interviews. Qualitative data were coded and analyzed using content
      analyses and grounded theory approach. Themes were then identified. Quantitative
      data were analyzed for frequencies and descriptives. Results: Fifty-four clients
      from 10 pantries participated in interviews/focus groups and completed
      questionnaires. Two major themes emerged: concern over obesity and other chronic
      diseases, and barriers to healthy eating. Several subthemes for barriers to
      healthy eating were identified: financial uncertainty, cost of healthy foods,
      lack of time, rationing food within family, lack of transportation, lack of
      adequate kitchen equipment, lack of nutrition knowledge and skills, and social
      support network. Conclusions: Issues identified above and those identified by
      others working with low-income populations need to be systematically addressed
      and incorporated into programs and nutrition education interventions for this
      group.

PMID- 30283834
TI  - Patterns of Communication Technology Utilization for Health Information Among
      Hispanics in South Carolina: Implications for Health Equity.
AB  - Background: Language, culture, geographic, social, and economic factors are
      associated with health disparities. Among more recent Hispanic immigrants,
      limited English proficiency and immigration status are barriers to health
      information and healthcare access. Improved access to culturally and
      linguistically tailored health information through technology could potentially
      enhance healthcare access and health outcomes. However, little is known about
      health information-seeking through technology among Hispanics in recent
      settlement areas. Purpose: The aim of this exploratory study was to describe
      patterns of self-reported utilization of technology for health information
      seeking among the growing Hispanic population in South Carolina (SC) over a
      period of 5 years. Methods: Descriptive, community-based, cross-sectional survey
      of 361 Hispanic adults residing in SC, conducted in 2011 and 2015/2016. Results:
      Reflective of reported national trends, self-reported accessibility and
      utilization of cellphones increased (89-96.6%) among this sample. Although
      computer ownership decreased (58-53.9%), internet utilization for health
      information-seeking increased (45-57.8%); more than 80% of participants indicated
      that they considered the internet a "good source of health information." The
      majority of participants in both time periods conducted health information
      searches in Spanish, although the reported access to English-language information
      increased over time. Conclusions: These findings illustrate the increasing access
      and utilization of technology for health information among Hispanics in SC,
      underscoring the need for broader dissemination of culturally and linguistically
      appropriate health information through accessible technology, including Spanish
      language websites. Recommendations for future research include examining
      relationships between technology access, health service access and utilization,
      and health behaviors among Hispanics in diverse geographic and social contexts.

PMID- 30283835
TI  - Racial and Ethnic Differences in Satisfaction with Care Coordination Among VA and
      non-VA Medicare Beneficiaries.
AB  - Purpose: Patients who have multiple sources of care are at risk for fragmented
      and uncoordinated care, which can lead to poorer outcomes. Veteran Medicare
      beneficiaries who use the Veterans Health Administration (VHA) system (VA users),
      particularly racial/ethnic minorities, often have complex medical conditions that
      may require care from multiple sources, leaving them especially vulnerable to the
      effects of fragmented care. We examined racial/ethnic differences in the level of
      satisfaction with care coordination among Medicare beneficiaries, comparing those
      who do and do not use the VHA healthcare system. Methods: We conducted a
      retrospective, pooled, cross-sectional study of Medicare beneficiaries using the
      2009-2011 Medicare Current Beneficiary Survey. The outcomes are self-reported
      satisfaction with care items related to three dimensions of care coordination:
      (1) integrated care, (2) care continuity, and (3) follow-up care. We present
      descriptive statistics and use generalized linear models to examine racial/ethnic
      differences across VA and non-VA users, after accounting for other demographic
      characteristics, health status, functional limitations, insurance coverage, and
      geographic variation. Results: VA users are more likely to be very satisfied with
      receiving both integrated and follow-up care compared with non-VA users. Despite
      the existence of significant racial/ethnic disparities in the likelihood of being
      very satisfied with receiving well-coordinated care in the larger Medicare
      population, racial/ethnic minority VA users are just as likely as White non
      Hispanics to be very satisfied with receiving well-coordinated care. Conclusions:
      Future research should continue to study care coordination among VA users and
      reasons for preferring the VA over other healthcare systems, especially among
      racial/ethnic minority groups.

PMID- 30283836
TI  - Background and Clinical Knowledge of Intimate Partner Violence: A Study of
      Primary Care Residents and Medical Students at a United States Medical School.
AB  - Purpose: Intimate partner violence (IPV) is a significant public health issue
      that affects the physical and mental health of victims. However, residents and
      medical students may not receive adequate training to effectively identify and
      intervene with patients who may be victims of IPV. The purpose of this study is
      to examine the background and clinical knowledge of IPV among primary care
      residents and medical students in the United States of America. Methods: Third
      and fourth year medial students (n=65) and primary care residents (n=60)
      participated in an online survey in 2013. Results: While the majority of the
      participants reported IPV was an important and relevant issue for their practice,
      approximately half of them had never talked about IPV with patients. Residents
      reported higher levels of background and knowledge of IPV than medical students.
      Knowing a victim of IPV, confidence about talking to patients about IPV, and
      talking to patients about IPV would be helpful to increase levels of background
      and knowledge of IPV. Conclusions: This study found that background and clinical
      knowledge of IPV can potentially affect physicians' approach with IPV victims.
      This study also demonstrated the need for future research in the development of
      effective programs and trainings to help bridge the gap between knowledge and
      implementation in medical practice.

PMID- 30283837
TI  - What an Emerging Trump Administration Means for Lesbian, Gay, Bisexual, and
      Transgender Health.
AB  - The policies of the Trump administration are likely to have direct and indirect
      implications for lesbian, gay, bisexual, and transgender (LGBT) health. With the
      assistance of a Republican-controlled Congress, President Trump may repeal
      President Obama's health reform law, undermine same-sex marriage laws and other
      nondiscrimination protections, reduce funding for research on sexual and gender
      minority health, and institutionalize discrimination through new legislation,
      such as the First Amendment Defense Act. Public health researchers, healthcare
      providers, and professional organizations must continue to combat discrimination
      and advocate for LGBT health equity under an emerging Trump presidency.

PMID- 30283838
TI  - Poverty and Breastfeeding: Comparing Determinants of Early Breastfeeding
      Cessation Incidence in Socioeconomically Marginalized and Privileged Populations
      in the FiNaL Study.
AB  - Purpose: Infant feeding differences are strongly tied to socioeconomic status.
      The goal of this study is to compare determinants of early breastfeeding
      cessation incidence in socioeconomically marginalized (SEM) and socioeconomically
      privileged (SEP) populations, focusing on birthing parents who intended to
      breastfeed. Methods: This cohort study includes data from 451 birthing parents in
      the Canadian province of Newfoundland and Labrador who reported intention to
      breastfeed in the baseline prenatal survey. Multivariate logistic regression
      techniques were used to assess the determinants of breastfeeding cessation at 1
      month in both SEM and SEP populations. Results: The analysis data included 73 SEM
      and 378 SEP birthing parents who reported intention to breastfeed at baseline. At
      1 month, 24.7% (18/73) in the SEM group had ceased breastfeeding compared to 6.9%
      (26/378) in the SEP group. In the SEP population, score on the Iowa Infant
      Feeding Attitude Scale (IIFAS) (odds ratio [OR] 3.33, p=0.01) was the sole
      significant determinant. In the SEM population, three significant determinants
      were identified: unpartnered marital status (OR 5.10, p=0.05), <1 h of skin-to
      skin contact after birth (OR 11.92, p=0.02), and negative first impression of
      breastfeeding (OR 11.07, p=0.01). Conclusion: These results indicate that
      determinants of breastfeeding cessation differ between SEM and SEP populations
      intending to breastfeed. Interventions intended on improving the SEM population's
      postpartum breastfeeding experience using best practices, increasing support, and
      ensuring at least 1 h of skin-skin contact may increase breastfeeding rates.

PMID- 30283839
TI  - A Pilot Study on the Psychosocial Health and Living Quality of Left-Behind
      Children in a Remote City of China.
AB  - Purpose: With the rapid economic development, China has undergone a large-scale
      migration, with many children left behind due to parental migration for better
      income. Little is known about the psychosocial health and living quality of the
      Chinese left-behind children (LBC) in remote cities, so this study aims at
      investigating the emotional and behavioral problems as well as the living
      qualities of LBC in remote cities of China. Methods: In this pilot cross
      sectional study, 45 schoolchildren (10-12 years old) from Guiyang, a remote city
      in China, were enrolled in the sampling. The Strength and Difficulties
      Questionnaire (SDQ) and Quality of Life Scale for Children and Adolescents
      (QLSCA) were used to evaluate the psychosocial health and living quality. The
      differences between LBC and control children and correlation factors were
      analyzed in this study. Results: LBC had a statistically significantly higher
      score in SDQ than in the control group with p-values that were all <0.01. The
      prosocial score in LBC was significantly lower than that of the control children
      (p<0.01). The scores on QLSCA were significantly lower for the LBC than for their
      counterparts (p<0.01). The emotional and behavioral problems (SDQ scores) and the
      living quality (QLSCA scores) are highly correlated. Conclusion: This preliminary
      study identified the severity of the psychosocial problem and the lower living
      quality with LBC in the remote city of China. This problem may relate to the
      lower education level of their caregivers. The LBC in remote cities of China need
      more psychosocial and educational support from schools and communities.

PMID- 30283841
TI  - Hispanic Youth Visits to Food and Beverage Company Websites.
AB  - Purpose: To measure disparities in exposure to food/beverage websites by Hispanic
      youth. Methods: Observational study using market research panel data compared
      frequency and time spent visiting food/beverage websites and the Internet overall
      for Hispanic and non-Hispanic children (6-11 years) and youth (6-17 years).
      Results: Hispanic children and youth, particularly Spanish-speaking youth, were
      less likely to visit the Internet overall, but more likely to visit
      food/beverages websites, compared with their non-Hispanic peers. Conclusions:
      Food and beverage company websites disproportionately appeal to Hispanic youth.
      Public health advocates and companies should take action to reduce Hispanic youth
      exposure to unhealthy food marketing online.

PMID- 30283840
TI  - Process Evaluation of a Peer-Driven, HIV Stigma Reduction and HIV Testing
      Intervention in Latino and African American Churches.
AB  - Purpose: Faith-based organizations may be effective in addressing HIV-related
      disparities, but few interventions have been implemented across diverse churches.
      The Facilitating Awareness to Increase Testing for HIV (FAITH) intervention
      harnessed peer leadership to decrease HIV stigma and promote HIV testing in
      African American and Latino congregations. A pilot study found more consistent
      effects among Latino congregations. This process evaluation evaluates
      implementation of FAITH to better understand the pilot study's findings. Methods:
      Data sources included HIV education and peer leader workshop evaluation forms,
      participant views of the community's perspective of HIV, and peer leader follow
      up interviews. Data were triangulated with systematic observation notes and
      analyzed using process-related themes of recruitment, reach, context,
      implementation, dose-delivered, and fidelity. Results: At the Latino churches
      (compared to the African American church), facilitators spent more time
      addressing community-based misconceptions about HIV. The peer leader model was
      well received, especially among Latino participants, and most said that after the
      workshop they felt comfortable speaking with others about HIV-related topics.
      Latino peer leaders reported speaking with up to 20 people within their social
      networks (particularly with family members); African Americans reported up to 4.
      Implementation challenges at the African American church may have contributed to
      the limited intervention effects. Nevertheless, we found the peer motivator model
      feasible and acceptable across diverse faith settings. Conclusion: Peer-based
      models within faith settings are promising for addressing HIV. However,
      differences among groups in HIV knowledge, social network characteristics and
      norms, and church preferences may influence overall effectiveness.

PMID- 30283842
TI  - Gone, But Not Forgotten? Survey of Resident Attitudes Toward a Cultural
      Standardized Patient Examination for a General Surgery Residency Program.
AB  - Purpose: Various tools have been utilized for cultural competency training in
      residency programs, including cultural standardized patient examinations.
      However, it is unknown whether residents feel the training they received has a
      long-term impact on how they care for patients. The purpose of this study was to
      assess whether surgical residents who participated in a cultural standardized
      patient examination view the experience as beneficial. Methods: Surgical
      residents who completed a standardized patient examination from Fall 2009 to
      Spring 2015 were asked to complete a 13-question survey assessing the following:
      (1) did participants feel prepared when dealing with patients from different
      cultural backgrounds, (2) did they feel the standardized patient experience was
      beneficial or improved their ability to care for patients, and (3) did they
      perceive that cultural competence was important when dealing with patients.
      Results: Sixty current/former residents were asked to participate and 24 (40%)
      completed the survey. All agreed cross-cultural skills were important and almost
      all reported daily interaction with patients from different cultural backgrounds.
      Sixteen participants (67%) reported the cultural standardized patient examination
      aided their ability to care for culturally dissimilar patients, and 13 (54%) said
      the training helped improve their communication skills with patients. Thirteen
      (54%) reported they would participate in another cultural standardized patient
      examination. Conclusion: Development of effective cultural competency training
      remains challenging. This study provides some preliminary results that
      demonstrate the potential lasting impact of cultural competency training.
      Participants found the skills gained from cultural standardized patient
      examinations helpful.

PMID- 30283843
TI  - Patterns in Liver-Related Health Outcomes with Hepatitis C Virus Treatments and
      Health Equity Implications for Decision Makers: A Cohort Analysis of Medicaid
      Patients.
AB  - Introduction: Hepatitis C virus (HCV) infection is a blood-borne communicable
      disease that, in perhaps 20% of cases, results in a chronic disease. However,
      traditional peginterferon/ribavirin therapies pose many adverse side effects that
      are difficult to tolerate, and many patients do not complete the therapy.
      However, healthcare access to these newer, efficacious treatments are reduced,
      due to inadequate or lack of coverage of direct acting antiviral (DAA)
      medication. The objective of this study was to evaluate the impact of HCV
      treatment regimens on outcomes of care for HCV-infected Medicaid beneficiaries
      without cirrhosis/liver disease scarring. Methods: A cohort analysis was
      performed to evaluate the changes in cirrhosis, hepatocellular carcinoma (liver
      cancer), and liver transplantation with use of HCV treatments in Medicaid
      beneficiaries with HCV, and was followed over a period of 10 years. The cohort of
      Medicaid beneficiaries and relevant variables were generated from published
      literature. Results: Finally, considering the impact on health expenditures due
      to improved access to new treatments in Medicaid beneficiaries, DAAs resulted in
      the lowest decompensated cirrhosis and hepatocellular carcinoma-related
      healthcare cost per person over the 10-year time frame the cohort was followed.
      Conclusions: The risk of liver-related disease is higher in patients with
      cirrhosis, as reaching treatment success results in continued disease
      progression, not normal health status; thus, liver cancer healthcare costs are
      higher in patients with cirrhosis, compared to those without cirrhosis.

PMID- 30283845
TI  - Academic Medicine's Responses to National Race-Related Events and Its Role in
      Civil Rights.

PMID- 30283844
TI  - Using Geospatial Analysis to Determine Access Gaps Among Children with Special
      Healthcare Needs.
AB  - Purpose: To examine geospatial gaps in identification and evaluation of children
      with special healthcare needs (CSHCN) within public child development centers
      (CDCs). Methods: A descriptive geospatial design was used to visually depict
      service gaps, proximity, and clustering of area-level sociodemographic attributes
      of Virginia counties, and patient-level data within each CDC. Results: Geospatial
      analysis shows population density of uninsured children against CDC resources.
      Data visualization facilitates policy advocacy based on the identification of
      care and screening gaps for CSHCN. Conclusion: This project illustrates the
      collaborative potential between researchers and Health Department members to
      identify gaps in access to care.

PMID- 30283846
TI  - The Harold Amos Medical Faculty Development Program: Evaluation of a National
      Program to Promote Faculty Diversity and Health Equity.
AB  - Purpose: The Harold Amos Medical Faculty Development Program (AMFDP), a national
      program of the Robert Wood Johnson Foundation, seeks to support academic
      physicians from historically disadvantaged backgrounds and serves as a model
      program for promoting faculty diversity and health equity. Our objective was to
      determine differences in scientific productivity, promotions and retentions, and
      leadership attainment among faculty applicants to this national minority faculty
      development program. Methods: Final-round interview applicants from 2003 to 2008
      were selected. Differences in publications, grants, promotions/retentions, and
      leadership positions through 2013 were compared between funded scholars and
      unfunded nonscholars. Semistructured interviews were conducted to identify
      factors that facilitated and hindered academic success. Results: A total of 124
      applicants (76 scholars and 48 nonscholars) who participated in final-round
      interviews from 2003 to 2008 were eligible. Scholars and nonscholars had similar
      number of publications. Scholars had greater number of grants and grant dollars,
      but differences were not significant after accounting for AMFDP program awards.
      Scholars were more likely to hold leadership positions (28% vs. 10%, p=0.02), but
      equally likely to be promoted (67% vs. 58%, p=0.32) and retained (84% vs. 75%,
      p=0.21). In interviews, all participants endorsed mentoring, funding, and
      nonscientific education to academic success, but scholars reported greater
      availability of leadership opportunities consequent to AMFDP. Conclusion: There
      were few differences in academic productivity attributable to a national faculty
      diversity program. However, program participants were more likely to endorse and
      attain leadership positions. Academic institutions should consider facilitating
      leadership development of minority faculty as a means of advancing health equity
      research and training.

PMID- 30283847
TI  - Exploring the Impact Factor: Medical Students Mentoring High School Students and
      Cultivating Cultural Humility.
AB  - Purpose: Diversity at all levels of medical training remains relatively stagnant,
      despite efforts to address equity in medical schools. Early career-specific
      mentoring may address barriers to the pursuit of medical education for students
      underrepresented in medicine (URiM). By surveying a program that engages medical
      students as drivers of career-specific mentorship for URiM high school students,
      this study evaluates medical student mentors' experiences mentoring and seeks to
      develop a mentorship curriculum. Methods: The authors describe a medical student
      led pipeline program, which connects medical students with URiM high school
      students. Medical student mentors participated in focus groups and gave written
      responses evaluating reasons for involvement, sociocultural attitudes, and skills
      needed for mentoring. Thematic analysis was applied. Results: Themes that emerged
      in this analysis include motivation to mentor, skills used to approach the
      mentoring relationship, and benefits to the mentor. Mentors felt their
      experiences had a high impact factor, and they employed dynamic discovery. It
      provided personal reward and a deeper understanding of disparities. Conclusion:
      Bringing medical school mentors together for peer to peer idea sharing, creating
      communities of practice, will help these students develop effective mentorship
      skills. A curriculum based on appreciative inquiry of mentors' strengths will
      enrich idea sharing, fostering cultural humility and avoiding burnout. Medical
      students involved in this program believe they gained benefits, including
      improving their mentorship skills, expanding their cultural humility, increasing
      their comfort with caring for underserved populations, and improving their
      ability to recognize health disparities.

PMID- 30283848
TI  - Psychosocial Factors Associated with Healthy and Unhealthy Interpregnancy
      Intervals.
AB  - Purpose: To examine the influence of psychosocial factors, including anxiety,
      depression, social support, maternal substance abuse, and intimate partner
      violence (IPV) on interpregnancy intervals (IPIs). Methods: B'more for Healthy
      Babies-Upton/Druid Heights is part of a citywide initiative to improve the health
      of at-risk pregnant women and their children. Participants with at least one
      prior birth completed baseline, postpartum, and 3-month follow-up surveys with
      questions about pregnancy, medical, and psychosocial history. Associations
      between IPI and the independent variables were assessed using chi-square analysis
      and analysis of variance. Multivariable multinomial logistic regression models
      examined significant associations while controlling for other independent
      variables and potential confounders. Results: Participants with current IPV were
      more likely to have a short IPI (odds ratio [OR]=13.1; 95% confidence interval
      [CI]=1.07-158.9; p=0.04) than healthy IPI. Women with family social support were
      more likely to have a healthy IPI (OR=5.88, 95% CI=1.02-31.25, p=0.05) than those
      without family social support. Maternal anxiety and depression did not
      significantly influence IPI. Conclusion: IPV increased the likelihood of having
      an unhealthy IPI among this population and family social support increased the
      likelihood of having a healthy IPI. Additional efforts to address IPV and enhance
      family social support may lead to improved pregnancy outcomes.

PMID- 30283849
TI  - Local Income Inequality, Individual Socioeconomic Status, and Unmet Healthcare
      Needs in Ohio, USA.
AB  - Purpose: Income inequality has been implicated as a potential risk to population
      health due to lower provision of healthcare services in deeply unequal countries
      or communities. We tested whether county economic inequality was associated with
      individual self-report of unmet healthcare needs using a state health survey data
      set. Methods: Adults residents of Ohio responding to the 2015 Ohio Medicaid
      Assessment Survey were included in the analysis. Ohio's 88 counties were
      classified into quartiles according to the Gini coefficient of income inequality.
      The primary outcome was a composite of self-reported unmet dental care, vision
      care, mental healthcare, prescription medication, or other healthcare needs
      within the past year. Unmet healthcare needs were compared according to county
      inequality quartile using weighted logistic regression. Results: The analytic
      sample included 37,140 adults. The weighted proportion of adults with unmet
      healthcare needs was 28%. In multivariable logistic regression, residents of
      counties in the highest (odds ratio [OR]=1.13, 95% confidence interval [CI]: 1.01
      1.26; p=0.030) and second-highest (OR=1.16, 95% CI: 1.04-1.30; p=0.010) quartiles
      of income inequality experienced more unmet healthcare needs than residents of
      the most equal counties. Conclusion: Higher county-level income inequality was
      associated with individual unmet healthcare needs in a large state survey. This
      finding represents novel evidence for an individual-level association that may
      explain aggregate-level associations between community economic inequality and
      population health outcomes.

PMID- 30283850
TI  - Is a Patient's Current Address of Record a Reasonable Measure of Neighborhood
      Deprivation Exposure? A Case for the Use of Point in Time Measures of Residence
      in Clinical Care.
AB  - Purpose: Interest is increasing in the use of geocoded patient address data to
      understand the effects that social determinants of health have on healthcare
      outcomes. Use of a patient's current address of record is often problematic given
      population mobility. Intragenerational economic mobility research suggests that
      patients will reside within neighborhoods with similar relative deprivation over
      time despite geographic mobility. The purpose of this study was to measure
      evidence of patient neighborhood deprivation persistence given a change in
      address of record. Methods: A retrospective cohort study of patients receiving
      active care in an integrated delivery system in a high-mobility United States
      region. Neighborhood deprivation was measured using a block-group level area
      deprivation index. Neighborhood deprivation persistence was measured as the
      probability that an individual with an address of record change remained within a
      neighborhood with a similar deprivation score. Logistic regression was used to
      conduct multivariate analysis. Results: Geographic mobility was highest among
      patients living in the most deprived neighborhoods versus least-deprived (odds
      ratio 1.75; 95% confidence interval: 1.71-1.79). Seventy-eight percent of all
      patients with a change of address did so to a neighborhood with a similar
      deprivation quintile. The probability that a random patient selected from the
      study had a change of address outside the same or neighboring quintile within a 1
      year period ranged from 2% to 13%. Conclusions: Neighborhood deprivation
      persistence was high among this population of patients from a high mobility
      region. A current address of record is a reasonable indicator of patient exposure
      to neighborhood deprivation within a 1-3-year timeframe that is useful in
      evaluating healthcare disparities.

PMID- 30283851
TI  - The Complexities of Assessing Language and Interpreter Preferences in Pediatrics.
AB  - Providing patients, parents, and families high-quality healthcare in the language
      of their choice is a fundamental component of patient-centered care in pediatric
      settings. However, language needs may be complex and dynamic, creating clinical
      and ethical challenges in cases of provider-parent discordance regarding the need
      for an interpreter. In this perspectives article, we use a clinical encounter as
      a foundation to discuss the intricacies of addressing language needs in
      pediatrics. We also describe the urgent need for further innovation and
      improvement in linguistic supports available to diverse patients and families.

PMID- 30283852
TI  - Making the Case for Addressing Health Disparities: What Drives Providers and
      Payers?
AB  - Purpose: The creation of the Centers for Medicare & Medicaid Services Office of
      Minority Health placed increased emphasis on federal efforts to address health
      disparities. Although the literature establishes a social justice case for
      addressing health disparities, there is limited evidence of this case being
      sufficient for businesses to invest in such initiatives. The purpose of this
      study was to better understand the "business case" behind an organization's
      investment in health disparity reduction work. Methods: We conducted six case
      studies (44 on-site interviews) with diverse private-sector provider and payer
      organizations. Results: While providers and payers cited business rationales for
      initiating disparity-focused efforts, their motivations differed. Conclusion: As
      federal entities address health disparities, and payment models shift from volume
      to value, engaging private stakeholders with the leverage to move the health
      disparities needle is of principal importance.

PMID- 30283853
TI  - The Limited English Proficient Population: Describing Medicare, Medicaid, and
      Dual Beneficiaries.
AB  - Purpose: The Limited English Proficient (LEP) population experiences well
      documented suboptimal health outcomes and substandard provider experiences. The
      lack of national estimates on the size of the LEP population relative to the
      healthcare setting makes examining health outcomes for this population very
      difficult. This analysis addresses this limitation by publishing population
      estimates for LEP persons enrolled in Medicare, Medicaid, and Duals (enrolled in
      Medicare and Medicaid). Focusing on the Medicare and Medicaid programs provides
      an important foundation as these programs are not only the largest insurers in
      the United States but are also governed by legislation that requires LEP persons
      to receive equitable access to care. Methods: Data from the 2014 American
      Community Survey Public Use Microdata Sample (ACS PUMS) were used to produce
      national estimates and measures of statistical accuracy for the LEP population
      enrolled in Medicare and/or Medicaid (LEPMM). Results: In 2014, there were
      approximately 8.7 million LEP persons enrolled in Medicare, Medicaid, or both
      programs (Duals). The LEPMM was concentrated along the western and eastern
      coastlines and the southwestern region, with California and New York each
      containing more than 1 million LEPMMs. The LEPMM was also highly diverse with
      varying disability status, and most were racial or ethnic minorities and elderly.
      Conclusion: These findings provide a foundation for measuring an understudied and
      at-risk population that will enable population health professionals to develop
      effective culturally and linguistically, and appropriate services and policies
      that address health disparities in the LEPMM.

PMID- 30283854
TI  - The Beyond the Books Program: Improving Medical Student Attitudes Toward the
      Underserved.
AB  - Purpose: To determine the impact of the Beyond the Books (BTB) program, a short
      term pre-clinical intervention, on medical student attitudes toward the
      underserved (MSATU). Methods: BTB was evaluated through a prospective cohort
      study using the validated MSATU questionnaire. Results: There were no significant
      MSATU total score differences between BTB students (n=13) and student controls
      (n=29) at the beginning of the program. At the program's conclusion, BTB
      participant MSATU total scores were significantly higher than those of controls
      (p<0.001). Conclusion: Although limited by selection methods, our MSATU data
      support the capability of short-term pre-clinical interventions to significantly
      improve medical student attitudes toward underserved communities.

PMID- 30283855
TI  - Differences in Referral Access to Care Between Gastrointestinal Subspecialty
      Patients: Barriers and Opportunities.
AB  - Purpose: Referral access to subspecialty care for patients with gastrointestinal
      (GI) diseases is not well defined, but has significant importance to patients. We
      hypothesized that patients experience barriers to care in two common
      gastroenterology subspecialties, Hepatology and Motility, in a university medical
      center. Methods: Two hundred thirteen clinic patients (mean age 46.5 years; 66.5%
      female; 85.6% Caucasians) completed a formatted questionnaire on access to care.
      Hepatology patients were older (49.7 years, p=0.008); motility patients
      predominantly female (76.8%, p<0.001). Gender distribution was even for
      hepatology (51.2% female). Both groups were overweight (mean body mass index
      28.4). Results: Patients waited a mean 89.5 days to be seen by a subspecialist.
      There were differences by subspecialty (107.6 days for motility vs. 64.3 days for
      hepatology, p=0.022). A larger percentage of motility patients were told nothing
      was wrong with them (16.8%, p<0.01) and could not be helped (42.1%, p=0.000).
      Conclusions: Access to care for subspecialty gastroenterology patients in a
      university center appears to be impacted by a number of variables. While there
      are similarities, differences exist between these two subspecialties. Motility
      patients were more likely to have been told they have nothing wrong with them,
      suffer setbacks financially, and suffer mood problems. Their wait time for
      appointments was also greater than hepatology patients. Further investigations of
      referral access for gastroenterology patients may yield additional insights into
      disease-specific barriers to accessing subspecialty care.

PMID- 30283856
TI  - Hispanic Breast Cancer Patients Travel Further for Equitable Surgical Care at a
      Comprehensive Cancer Center.
AB  - Purpose: Disparities in surgical breast cancer care have been documented for
      racial and ethnic minorities. On average, these minorities are less likely to
      utilize National Cancer Institute (NCI)-designated cancer centers and travel
      shorter distances to receive care. With the growing population of Hispanic
      patients in California, we analyzed the travel distance and surgical care of
      Hispanic and non-Hispanic patients at our large referral cancer center. Methods:
      Patients included were those who initiated treatment for a new diagnosis of
      ductal carcinoma in situ or invasive breast cancer at our NCI-designated cancer
      center during the period 2010-2014. Ethnicity was dichotomized as Hispanic and
      non-Hispanic. Google Maps were used to determine the distance from patient zip
      code to our institution, classified as 0-10, 10-30, 30-60, and >60 miles.
      Results: A total of 1765 non-Hispanic and 173 Hispanic patients were identified.
      Clinical stage by tumor size and nodal status were comparable between the two
      groups. Hispanic patients were younger (p<0.001) and more had Medicaid insurance
      (p<0.001). Hispanic patients traveled further when compared with non-Hispanics
      (p<0.001). In non-Hispanics and Hispanics, rates of breast conservation were
      57.4% and 52.3% (p=0.30), unilateral mastectomy 34.2% and 36.2% (p=0.44),
      bilateral mastectomy 8.4% and 11.5% (p=0.24), and immediate postmastectomy
      reconstruction 42.6% and 50.6% (p=0.34), respectively. Hispanic ethnicity was not
      associated with different odds of receiving breast conservation (odds ratio [OR]
      1.01, confidence interval [CI] 0.73-1.40), unilateral mastectomy (OR 1.05, CI
      0.75-1.44), bilateral mastectomy (OR 1.37, CI 0.81-2.31), or immediate
      postmastectomy breast reconstruction (OR 1.27, CI 0.86-1.88), when compared with
      non-Hispanic ethnicity, after controlling for patient age, insurance status, and
      distance traveled. Conclusions: Surgical care was similar for Hispanic and non
      Hispanic patients treated at our NCI-designated cancer center. However, this
      Hispanic population traveled further than non-Hispanic patients. Our findings
      suggest that accessibility to transportation and institutional practices are
      instrumental in delivering equitable breast cancer surgical care for Hispanic
      patients.

PMID- 30283857
TI  - Equity Arguments in News Reporting on School Nutrition Policy.
AB  - Purpose: In two related studies, we examined how equity-based arguments featured
      in news debate over federal school nutrition policy. Methods: We conducted
      content analyses of national and local print and broadcast news (September 1,
      2014-December 31, 2015), examining arguments rooted in appeals about equity
      and/or disparities. Results: Equity and/or disparities appeals appeared in 24%
      television, 14% national print, and 5% local print stories. Socioeconomic
      inequities were mentioned most; racial/ethnic inequities appeared minimally.
      Conclusions: Neither equity nor disparity featured prominently in this news
      debate over policy created to address children's nutritional inequities. When
      included, arguments focused on overcoming inequities' effects rather than
      addressing root causes.

PMID- 30283858
TI  - Sociodemographic Characteristics of Women Able to Obtain Medication Abortion
      Before and After Ohio's Law Requiring Use of the Food and Drug Administration
      Protocol.
AB  - Purpose: In 2011, a law went into effect in Ohio that regulates how abortion care
      providers can offer medication abortion to their patients. We sought to evaluate
      changes in sociodemographic characteristics of Ohio medication abortion patients
      before and after the implementation of this law. Methods: We used a retrospective
      cohort design, comparing characteristics of women obtaining a medication abortion
      at four abortion facilities before and after the law. We used chart data from
      January 2010 to January 2011 and February 2011 to October 2014. For any
      significant changes in sociodemographics found before and after the law, we used
      stratified cross-tabulations to disentangle whether they were likely related to
      the restricted gestational limit imposed by the law (lowered from 9 to 7 weeks
      gestation), or whether they were likely related to other burdens brought on by
      the law, such as increased costs and visits. Results: Women obtaining a
      medication abortion after the law were more likely to be older (p=0.01), have
      higher levels of education (p<0.001), be of white race (p<0.001), have private
      insurance (p=0.001), have no children (p=0.002), and reside in a higher income
      zip code (p=0.03). Both the reduced gestational limit and the increased costs and
      visits likely contributed to declines among black women and women with lower
      levels of education. The reduced gestational limit for medication abortion likely
      contributed to a decline among younger women and Medicaid recipient groups. The
      increased costs and visits imposed by the law likely contributed to the decline
      in medication abortion among women with no insurance and women with children.
      Conclusion: The lower gestational limit, higher cost, and time and travel burdens
      exacted by Ohio's medication abortion law were associated with disproportionate
      reductions in medication abortion among the most disadvantaged groups. The law
      was associated with reduced access among women who were younger, of black race,
      less educated, and in lower socioeconomic groups.

PMID- 30283859
TI  - Healthcare Experiences of Underrepresented Lesbian and Bisexual Women: A Focus
      Group Qualitative Study.
AB  - Purpose: To understand the complex healthcare experiences of women identifying as
      lesbian or bisexual. who are also women of color, veterans, and/or 65 years of
      age and older. Methods: Inclusion criteria were age 25 or older, Los Angeles
      County resident, self-identification as a lesbian or bisexual woman, and as an
      African American, Latina, Asian-Pacific Islander, and/or a veteran. For the age
      65 years and older group, participants were eligible regardless of their veteran
      status or race/ethnicity. Five focus groups were conducted (n=35) and the same
      questions were asked addressing their comfort interacting with healthcare
      providers, the provider knowing their sexual orientation, characteristics of a
      perfect provider, and barriers to care. Structured qualitative analyses were
      performed. Results: Participants identified concerns that providers often hold to
      heterosexual cultural norms. Participants varied on preferences for providers of
      the same race/ethnicity as themselves. Lesbians who are 65 years and older
      identified legal barriers as major concerns. All groups identified incorrect
      provider assumptions about sexual orientation and sexual practices as frequently
      compromising their care. Participants supported the idea of certification for
      providers skilled in lesbian, gay, bisexual, transgender, and queer (LGBTQ)
      health, but expressed skepticism that such programs would necessarily result in
      better care. Conclusion: Healthcare provider trainings need to address the
      specific concerns and experiences of underrepresented lesbian and bisexual women.
      Healthcare environments must be transformed to effectively address their needs.
      More research is needed on the separate healthcare experiences of specific
      marginalized populations related to their sexual orientation and/or gender
      identity.

PMID- 30283860
TI  - Maternal Diet and Morbidity Factors Associated with Low Birth Weight in Haiti: A
      Case-Control Study.
AB  - Objective: A matched, case-control study was conducted to examine the association
      between development of low birth weight (LBW) and maternal factors, including
      dietary intake, comorbidities, and socioeconomic factors, among women in Cap
      Haitien, Haiti. Design: Mothers who delivered LBW babies; defined as <=2.5 kg,
      were identified by review of the medical record and matched to mothers of similar
      age, parity, with normal birth weight (NBW) babies. A survey was administered
      consisting of Women's Dietary Diversity Score (WDDS), maternal reporting of
      comorbidities, income, and educational level. Subjects: Women were eligible if
      they delivered and had newborns weighed within the last 2 years. Total study
      participants consisted of 32 cases and 34 controls matched for age, parity, and
      month of delivery. Results: Mothers who consume eggs were 78% less likely to have
      given birth to a LBW infant (OR 0.22 (95% CI: 0.05-0.87). Mothers with NBW babies
      had a nonsignificant trend towards higher WDDS. The prevalence of hypertension in
      mothers who were seen in the clinic at least once over the past 2 years was found
      to be 27%, and 78% of mothers were not aware of their diagnosis. Conclusion:
      Enhancing maternal nutrition during pregnancy has broad implications for reducing
      LBW, improving fetal health and reducing fetal predilection for chronic diseases
      in adulthood. Longitudinal prospective studies are needed to evaluate the
      selective benefit of eggs and other high-quality foods in protecting fetal
      growth. Efforts to improve knowledge and awareness of hypertension in Haiti
      should be undertaken.

PMID- 30283861
TI  - Addressing Lupus Health Disparities: The MONARCAS Community and Academic
      Collaborative Program.
AB  - Purpose: The Centers for Disease Control (CDC) Popular Opinion Leader (POL) model
      was implemented in a lupus education program (MONARCAS) for the Latino community.
      The program aim was to increase lupus awareness by training high school students,
      community health workers, and parents. Methods: A curriculum was developed
      training POLs to disseminate concepts about lupus signs and symptoms. Pre- and
      post-program questions assessed lupus knowledge and message dissemination.
      Results: POL groups represented distinct demographic characteristics with Spanish
      or English language dominance. POLs reported increased lupus knowledge and
      program satisfaction. Conclusions: Future program goals should aim to increase
      understanding and improving access to care for Latino communities affected by
      lupus.

PMID- 30283862
TI  - Disparities in Cardiovascular Risk Factors in Northern Plains American Indians
      Undergoing Coronary Artery Bypass Grafting.
AB  - Objectives: Heart disease is the leading cause of death in American Indians
      (AIs). For AI patients with severe coronary artery disease requiring coronary
      artery bypass graft (CABG) surgery, little data exist. The purpose of this study
      was to evaluate short-term outcomes of Northern Plains AI undergoing CABG and
      identify variations in patient presentation. Methods: All patients undergoing
      isolated CABG between June 2012 and June 2017 were studied. Seventy-four AI and
      1236 non-American Indian (non-AI) patients were identified. Risk factors,
      preoperative characteristics, cardiac status, procedural information, and
      outcomes were collected. Univariate analysis comparing short-term clinical
      outcomes between AI and non-AI populations was performed. Multivariable logistic
      regression models were constructed and outcome differences assessed. Unadjusted
      Kaplan-Meier survival estimates were produced using 5-year survival data.
      Results: AI patients presented with increased risk factors, including higher
      rates of diabetes mellitus (AI 63.5% vs. non-AI 38.7% p=< 0.001) and
      smoking/tobacco use (AI 60.8% vs. non-AI 20.0% p=> 0.001). Seventy-nine percent
      of AI patients resided on or near federal reservations and presented from rural
      locations. Internal mammary artery (IMA) graft use in both groups was high (AI
      95.9% vs. non-AI 94.9% p=0.904), and multiarterial grafting with left internal
      mammary artery and radial artery use was common in both groups (AI 67.6% vs. non
      AI 69.6% p=0.814). No significant differences in unadjusted 30-day mortality or
      short-term outcomes were detected. Adjusted Kaplan-Meier survival curves were
      similar between race groups up through 5 years after CABG (p-value=0.38).
      Conclusion: AIs presented with significantly more risk factors for cardiovascular
      disease compared with the general population, with especially high rates of
      insulin-dependent diabetes and active tobacco use. Despite this, outcomes were
      similar between groups. In propensity-matched groups, AIs were at decreased risk
      for prolonged length of stay and combined morbidity/mortality. In contrast to
      previous reports, AI racial identity did not adversely affect survival up to 5
      years after CABG.

PMID- 30283863
TI  - Internet Access Influences Community Clinic Portal Use.
AB  - Purpose: To assess whether individuals attending a community clinic had the
      necessary Internet access and experience to use the patient portal, while
      examining covariates of education, income, and self-perception of health with
      past and anticipated portal use. Methods: Adults attending an urban, community
      primary care clinic were invited to participate in a brief survey assessing
      current Internet access and use, past portal use, and anticipated future portal
      use. Survey responses were analyzed using descriptive and multivariate
      statistics. Results: One hundred fifteen participants ranging in age from 18 to
      84 years (mean 42.1, standard deviation 17.1) completed the survey; 6 (5%) in
      Spanish. Thirty-five (30%) self-identified as Latino; 12 (10%) as Asian; and 20
      (17%) as other. Almost 80% reported their health as good or better. Although 38%
      reported some college and 47% reported being college graduates, 60% reported
      household incomes were <$50,000. Most (87%) used the Internet for >1 year. Fewer
      than half (42%) had past portal use, with significant differences associated with
      weekly Internet use (Fisher's exact=9.59; p=0.02) and smart phone access
      (Fisher's exact=6.15; p=0.02). Computer Internet access was significantly
      associated with income (Fisher's exact=16.91; p<0.001). Logistic regression
      identified that computer Internet access was a significant predictor (odds ratio
      9.9 (95% confidence interval: 1.7-58.8) of future portal use, controlling for
      smart phone use, health status, gender, and age. Conclusions: Among this highly
      educated but lower economic sample, computer Internet access and smart phone
      access were associated with past portal use and anticipated future use.

PMID- 30283864
TI  - Developing Smokeless Tobacco Prevention Messaging for At-Risk Youth: Early
      Lessons from "The Real Cost" Smokeless Campaign.
AB  - Introduction: Smokeless tobacco (SLT) use continues to be a significant public
      health challenge in the United States, particularly among young males in rural
      areas, where use remains disproportionately high. In support of the U.S. Food and
      Drug Administration's first nationwide SLT public education campaign, formative
      research was conducted to inform campaign strategy development and test creative
      concepts. Methods: Qualitative research methods were used to inform the strategic
      direction of the campaign, identify salient message themes, and refine creative
      concepts. Focus groups were conducted with 252 rural male youth ages 12-17 in
      seven states. Groups were organized by SLT status (i.e., at-risk for initiating
      vs. experimenting with SLT) and age group. Results: SLT use is culturally
      ingrained in rural communities, and rural youth are commonly exposed to SLT
      through close relationships. Among this group, "dipping" (SLT use) has strong
      cultural significance and is perceived as safe. Members of the target audience
      are receptive to straightforward facts delivered by authentic messengers about
      the potentially harmful consequences of SLT use, specifically those that leverage
      the progression of short-term consequences (e.g., white patches) to long-term
      health effects. Conclusions: This study addresses SLT literature gaps related to
      youth knowledge, attitudes, and beliefs by summarizing audience learnings from
      formative research that was used to develop the first national SLT public
      education campaign.

PMID- 30283865
TI  - The Application of Medical Artificial Intelligence Technology in Rural Areas of
      Developing Countries.
AB  - Background: Artificial intelligence (AI) is a rapidly developing computer
      technology that has begun to be widely used in the medical field to improve the
      professional level and efficiency of clinical work, in addition to avoiding
      medical errors. In developing countries, the inequality between urban and rural
      health services is a serious problem, of which the shortage of qualified
      healthcare providers is the major cause of the unavailability and low quality of
      healthcare in rural areas. Some studies have shown that the application of
      computer-assisted or AI medical techniques could improve healthcare outcomes in
      rural areas of developing countries. Therefore, the development of suitable
      medical AI technology for rural areas is worth discussing and probing. Methods:
      This article reviews and discusses the literature concerning the prospects of
      medical AI technology, the inequity of healthcare, and the application of
      computer-assisted or AI medical techniques in rural areas of developing
      countries. Results: Medical AI technology not only could improve physicians'
      efficiency and quality of medical services, but other health workers could also
      be trained to use this technique to compensate for the lack of physicians,
      thereby improving the availability of healthcare access and medical service
      quality. This article proposes a multilevel medical AI service network, including
      a frontline medical AI system (basic level), regional medical AI support centers
      (middle levels), and a national medical AI development center (top level).
      Conclusion: The promotion of medical AI technology in rural areas of developing
      countries might be one means of alleviating the inequality between urban and
      rural health services. The establishment of a multilevel medical AI service
      network system may be a solution.

PMID- 30283866
TI  - Chinese Immigrant Women's Attitudes and Beliefs About Family Involvement in
      Women's Health and Healthcare: A Qualitative Study in Chicago's Chinatown.
AB  - Purpose: Healthcare utilization and health-seeking behaviors of Chinese American
      immigrant women may be influenced by longstanding cultural perspectives of family
      roles and relationships. An understanding of Chinese immigrant women's
      perceptions of family social support in health and how these beliefs manifest in
      healthcare utilization and help-seeking behaviors is critical to the development
      of culturally appropriate health interventions. Focusing on a sample of Chinese
      women in Chicago's Chinatown, this qualitative study seeks to describe women's
      attitudes and beliefs about spouse and adult children's involvement in women's
      health and healthcare. Methods: We conducted six focus groups among 56 Chinese
      speaking adult women in Chicago's Chinatown between July and August 2014. Focus
      groups were transcribed, coded, and analyzed for emergent themes. Results: Women
      reported that their adult children supported their health and healthcare
      utilization by helping them overcome language and transportation barriers, making
      and supporting decisions, and providing informational and instrumental support
      related to diet and nutrition. Women viewed these supports with mixed
      expectations of filial piety, alongside preferences to limit dependency and help
      seeking because of concern and emotional distress regarding burdening adult
      children. Women's expectations of the spouse involvement in their healthcare were
      low and were shaped by avoidance of family conflict. Conclusion: Findings inform
      opportunities for the development of culturally appropriate interventions to
      enhance Chinese immigrant women's health and healthcare. These include patient
      navigation/community health worker programs to promote self-management of
      healthcare and family-centered strategies for enhancing family social support
      structures and reducing family conflict.

PMID- 30283867
TI  - Racial Disparities and the Effect of County Level Income on the Incidence and
      Survival of Young Men with Anal Cancer.
AB  - Purpose: Prior studies have identified a racial disparity in incidence and
      survival of squamous cell carcinoma of the anus (SCCA) in the young African
      American male population. We aim to determine whether racial disparities are
      independent of income and urban location. Methods: The National Cancer
      Institute's Surveillance of Epidemiology and End Results database was queried for
      data on patients with SCCA for the years of 2000-2013. Cox regression was used to
      determine the effect of race, county median family income, rural-urban continuum,
      and stage of disease on overall survival. Results: The incidence rate of SCCA was
      significantly higher in black men <50 years old than in white men. Black race had
      a hazard ratio of 1.55 (confidence interval [CI] 1.33-1.81) when controlling for
      age, stage, income, and urban-rural status. Each $10,000 increase in county
      median family income was protective with a hazard ratio of 0.90 (CI 0.86-0.94).
      Residence in a metropolitan area did not significantly affect survival.
      Conclusions: The lower survival of black men <50 years old with SCCA is
      independent of income, urban location, and stage of disease. Further efforts are
      needed to target this at-risk population and the authors suggest wide application
      of previously validated screening programs for anal dysplasia.

PMID- 30283869
TI  - Provision of Reproductive Healthcare to Women with Disabilities: A Survey of
      Obstetrician-Gynecologists' Training, Practices, and Perceived Barriers.
AB  - Purpose: The purpose of this study was to document current awareness, attitudes,
      and training regarding the care of women with disabilities by obstetrician
      gynecologists (ob-gyns) and explore barriers that may explain observed
      discrepancies in care. Methods: One thousand ob-gyns, including 500 members of
      the Collaborative Ambulatory Research Network (CARN), were surveyed on practice
      accessibility, training, awareness, barriers, beliefs, comfort, challenges,
      practices, contraceptive counseling, and preconception/pregnancy counseling.
      Results: CARN, 49.0%, and non-CARN, 19.4%, members completed the survey for an
      overall response rate of 33.9%. Most respondents indicated feeling "somewhat"
      (57.5%) or "very" (21.9%) aware of the special healthcare needs of women with
      disabilities. Only 17.2%, however, received any information or training on the
      provision of healthcare to women with disabilities. Eighty-one percent agreed
      somewhat or strongly that women with disabilities are less likely to receive
      comprehensive reproductive healthcare. Respondents who provided contraceptive
      counseling (94.3%) initiated it with women of reproductive age who did not have a
      disability more frequently than those who had a disability. Finally, only 19.3%
      felt "definitely" adequately equipped to manage the pregnancies of women with
      disabilities. Conclusion: Women with disabilities require reproductive healthcare
      no less than women without disabilities; however, the evidence consistently
      identifies disparities. This study suggests that while ob-gyn providers are aware
      of these issues, they lack adequate training and resources to provide equal care.

PMID- 30283868
TI  - Alternatives in Assessing Mental Healthcare Disparities Using the Behavioral Risk
      Factor Surveillance System.
AB  - Purpose: Identification of mental healthcare disparities through scales or
      questionnaires is an initial step to improve mental healthcare equity. This study
      was designed to investigate the performance of a single-item question relative to
      two psychiatric scales with multiple items in assessing mental healthcare
      disparities among U.S. adults using the Behavioral Risk Factor Surveillance
      System (BRFSS) data. Methods: The current depression (CD) and serious
      psychological distress (SPD) were analyzed in 2010 and 2012 with the BRFSS using
      two multiple-item scales in selected states. Receipt of mental health diagnosis
      and mental health treatment was ascertained respectively. In both years, a single
      item of the number of mentally unhealthy days from Centers for Disease Control
      Health-Related Quality of Life-4 (CDC-HRQOL-4) core questions was used to
      ascertain frequent mental distress (FMD) in all states. Logistic regression was
      used to identify mental healthcare disparities among subpopulations. The t-test
      was used to analyze missing data patterns. Results: Among adults who experienced
      FMD or CD in 2010, men, persons 65 years of age or older, non-Hispanic Blacks,
      persons who were currently or never married, and persons who were employed had a
      lower likelihood of receiving diagnosis of depression. Among adults who
      experienced FMD or SPD in 2012, men, persons 65 years of age or older, Hispanics
      and Blacks, persons who were currently employed or homemakers/students, and
      persons without healthcare coverage had a lower likelihood to receive mental
      health treatment. The missing rates of FMD were 1.8% (2010) and 1.4% (2012),
      while the missing rates of Patient Health Questionnaire 8 (PHQ-8) and Kessler 6
      (K6) were 12.8% (2010) and 17.4% (2012). The samples with missing data were
      different from those without. Conclusions: The single-item question is a valuable
      alternative in a large population surveillance to identify vulnerable
      subpopulations for lower mental health diagnosis and treatment.

PMID- 30283870
TI  - Barriers to Mental Health Treatment Utilization in Wards 7 and 8 in Washington,
      DC: A Qualitative Pilot Study.
AB  - Purpose: There is a paucity of data on barriers to mental health treatment
      utilization among residents of Wards 7 and 8 in Washington, DC, despite exposure
      to many environmental factors that are associated with poor mental health
      outcomes and the high prevalence of mental health problems among residents. The
      objective of this study was to examine barriers to mental healthcare utilization
      among residents of Wards 7 and 8. Methods: This study included semi-structured,
      in-depth interviews with five key informants who lived or spent significant time
      in Wards 7 or 8 in Washington, DC, which are the wards served by Paving the Way
      MSI, a behavioral health clinic that served as a partner organization in the
      study. Results: Barriers to mental health treatment utilization existed at a
      variety of social-ecological levels, including the individual/interpersonal
      level, the provider/mental health system level, the community level, and the
      societal level. Major barriers included fear and trust/distrust in the medical
      system, lack of social support, the model of mental healthcare, lack of patient
      centered care, limited access to mental health services, stigma of mental illness
      and mental health treatment, and poverty. Conclusion: This study highlights the
      need to address barriers to mental health treatment utilization at multiple
      social-ecological levels. Future studies should examine perspectives from
      residents with mental health problems in these wards to gain a more thorough
      understanding of the barriers to treatment. Funding is needed to support efforts
      to increase mental health treatment utilization among residents of Wards 7 and 8.

PMID- 30283871
TI  - Factors Associated with Human Papillomavirus Vaccination Among Diverse
      Adolescents in a Region with Low Human Papillomavirus Vaccination Rates.
AB  - Introduction: This study assesses the sociodemographic facilitators and barriers
      to human papillomavirus (HPV) vaccination for diverse teens in a region with low
      HPV vaccination rates. Materials and Methods: In this community-based
      participatory research study, we surveyed adult family members of teens aged 11
      17 years from African American, African refugee, American Indian/Alaskan Native,
      Hispanic/Latino, and Native Hawaiian/Pacific Islander community groups in Salt
      Lake City, Utah. Bivariate analyses assessed associations between
      sociodemographic characteristics and, respectively, HPV vaccine receipt and
      intentions for vaccination. Barriers to vaccination were also investigated.
      Results: Only 20% of participants had vaccinated at least one of their children
      with at least one dose of the HPV vaccine. HPV vaccination was significantly
      related to caregiver age (p=0.035), race/ethnicity (p=0.001), educational
      attainment (p=0.006), annual household income (p=0.0454), years in the United
      States (p=0.023), and caregiver parent birthplace (p=0.008). Among caregivers
      with unvaccinated children, intention to vaccinate was significantly related to
      race/ethnicity (p=0.048 for daughters; p=0.003 for sons), caregiver parent
      birthplace (p=0.023 for sons), health insurance coverage (p=0.028 for daughters;
      p=0.047 for sons), and type of health insurance coverage (p=0.008 for sons). The
      most frequently cited barriers to HPV vaccination were lack of knowledge about
      the HPV vaccine, costs, side effects, and child not being sexually active.
      Conclusions: Our results show substantially lower HPV vaccine coverage than both
      national and state rates, signaling the urgent need for multipronged HPV
      vaccination interventions within these communities; strategies are discussed.

PMID- 30283872
TI  - Importance of Shared Decision-Making for Vulnerable Populations: Examples from
      Postmastectomy Breast Reconstruction.
AB  - Shared decision-making (SDM) is a process through which patients and providers
      collaborate to select a treatment option that aligns with patients' preferences
      and clinical context. SDM can improve patients' decision quality and
      satisfaction. However, vulnerable populations face barriers to participation in
      SDM, which exacerbates disparities in decision quality. This perspective article
      discusses SDM with vulnerable patients, using examples from patients who made
      decisions about postmastectomy breast reconstruction. We offer several strategies
      for clinical practice, medical education, and research to ensure that movements
      to engage patients in SDM do not exclude already marginalized groups.

PMID- 30283873
TI  - It Works, But For Whom? Examining Racial Bias in Carding Experiences and
      Acceptance of a County Identification Card.
AB  - Purpose: Policies that restrict access to U.S. government-issued photo
      identification (ID) cards adversely affect multiple marginalized communities.
      This context impedes access to health-promoting resources that increasingly
      require government-issued IDs and exacerbates health inequities. In 2015,
      Washtenaw County, Michigan, implemented the Washtenaw ID to improve access to
      resources contingent upon having an ID. We employed an audit study to examine
      whether Washtenaw ID users experienced racially biased treatment in carding
      experiences and acceptance of the Washtenaw ID. Methods: Seven 25- to 32-year-old
      mystery shoppers (two Latina, three black, and two white women) attempted to
      purchase a standardized basket of goods, including an age-restricted item in
      Washtenaw County stores (n=130 shopping experiences). We examined whether
      experiences of being asked for ID and acceptance of the Washtenaw ID varied by
      race/ethnicity. Results: Each shopper visited 9-22 stores. Shoppers were asked
      for ID in 63.1% of shopping experiences. Of these, the Washtenaw ID was accepted
      91.5% of the time. Among those who were asked for ID, a higher percentage of
      Latina (16.0%) shoppers had their Washtenaw IDs rejected than black (6.3%) and
      white (4.0%) shoppers, although differences were not statistically significant
      (p=0.27). Latina shoppers had 2.9 times the odds of receiving a comment about
      their Washtenaw ID relative to white shoppers (OR=2.92, p=0.08), comments that
      were nonpositive. Conclusion: Local IDs may improve access to resources
      contingent upon having an ID. However, racialization processes, including anti
      immigrant sentiments, may inhibit the mitigating goal of local IDs. Continued
      attention to the health equity impacts of equity-driven interventions is
      warranted.

PMID- 30283875
TI  - Rural-Urban Differences in Risk Factors for Motor Vehicle Fatalities.
AB  - Purpose: To examine rural-urban differences in motor vehicle fatality (MVF) risk
      factors. Methods: We used 2017 County Health Rankings data to run stratified
      regression models to estimate county-level correlates of motor vehicle fatalities
      (MVFs) by rural and urban location. Results: Rural counties have higher rates of
      MVFs than urban counties (22 vs. 14 per 100,000, p<0.001). Physical inactivity
      and uninsurance were associated with higher rates of MVFs, as was having a more
      racially or ethnically concentrated population and larger percentages of younger
      or older adults. Conclusion: Interventions to reduce MVFs should take geographic
      location and population composition into account.

PMID- 30283876
TI  - The Birth of JBMR Plus.

PMID- 30283874
TI  - Racism, African American Women, and Their Sexual and Reproductive Health: A
      Review of Historical and Contemporary Evidence and Implications for Health
      Equity.
AB  - Background: The sexual and reproductive health of African American women has been
      compromised due to multiple experiences of racism, including discriminatory
      healthcare practices from slavery through the post-Civil Rights era. However,
      studies rarely consider how the historical underpinnings of racism negatively
      influence the present-day health outcomes of African American women. Although
      some improvements to ensure equitable healthcare have been made, these historical
      influences provide an unexplored context for illuminating present-day
      epidemiology of sexual and reproductive health disparities among African American
      women. Methods: To account for the unique healthcare experiences influenced by
      racism, including healthcare provision, we searched online databases for peer
      reviewed sources and books published in English only. We explored the link
      between historical and current experiences of racism and sexual and reproductive
      health outcomes. Results: The legacy of medical experimentation and inadequate
      healthcare coupled with social determinants has exacerbated African American
      women's complex relationship with healthcare systems. The social determinants of
      health associated with institutionalized and interpersonal racism, including
      poverty, unemployment, and residential segregation, may make African American
      women more vulnerable to disparate sexual and reproductive health outcomes.
      Conclusions: The development of innovative models and strategies to improve the
      health of African American women may be informed by an understanding of the
      historical and enduring legacy of racism in the United States. Addressing sexual
      and reproductive health through a historical lens and ensuring the implementation
      of culturally appropriate programs, research, and treatment efforts will likely
      move public health toward achieving health equity. Furthermore, it is necessary
      to develop interventions that address the intersection of the social determinants
      of health that contribute to sexual and reproductive health inequities.

PMID- 30283878
TI  - Bilateral Avascular Necrosis of the Femoral Head in Fibrous Dysplasia.
AB  - Fibrous dysplasia (FD) is an uncommon benign skeletal disorder, characterized by
      bone pain, deformities, and the development of pathological fractures. It is
      caused by osteoblastic lineage differentiation defects, leading to the
      replacement of normal bone with benign disorganized fibrous connective tissue.
      Avascular necrosis (AVN) of the femoral head is an insidious condition that can
      often be challenging to diagnose in its early stages. The pathogenesis of AVN is
      not well understood; however, it causes femoral head ischemia and collapse, often
      requiring hip arthroplasty. We report the first case of FD and bilateral AVN of
      the femoral head in the absence of an antecedent fracture. We postulate several
      mechanisms to explain how FD may result in AVN; however, further research is
      required to understand its pathophysiology and thus to guide clinical practice.
      (c) 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf
      of the American Society for Bone and Mineral Research.

PMID- 30283877
TI  - Identification of Chloride Intracellular Channel Protein 3 as a Novel Gene
      Affecting Human Bone Formation.
AB  - Osteoporosis is a common skeletal disorder characterized by low bone mass leading
      to increased bone fragility and fracture susceptibility. The bone building cells,
      osteoblasts, are derived from mesenchymal stromal cells (MSCs); however, with
      increasing age osteogenic differentiation is diminished and more adipocytes are
      seen in the bone marrow, suggesting a shift in MSC lineage commitment.
      Identification of specific factors that stimulate osteoblast differentiation from
      human MSCs may deliver therapeutic targets to treat osteoporosis. The aim of this
      study was to identify novel genes involved in osteoblast differentiation of human
      bone marrow-derived MSCs (hMSCs). We identified the gene chloride intracellular
      channel protein 3 (CLIC3) to be strongly upregulated during MSC-derived
      osteoblast differentiation. Lentiviral overexpression of CLIC3 in hMSCs caused a
      60% increase of matrix mineralization. Conversely, knockdown of CLIC3 in hMSCs
      using two short-hairpin RNAs (shRNAs) against CLIC3 resulted in a 69% to 76%
      reduction in CLIC3 mRNA expression, 53% to 37% less alkaline phosphatase (ALP)
      activity, and 78% to 88% less matrix mineralization compared to scrambled
      control. Next, we used an in vivo human bone formation model in which hMSCs
      lentivirally transduced with the CLIC3 overexpression construct were loaded onto
      a scaffold (hydroxyapatite-tricalcium-phosphate), implanted under the skin of NOD
      SCID mice, and analyzed for bone formation 8 weeks later. CLIC3 overexpression
      led to a 15-fold increase in bone formation (0.33% versus 5.05% bone area
      relative to scaffold). Using a Clic3-His-tagged pull-down assay and liquid
      chromatography-mass spectrometry (LS/MS)-based proteomics analysis in lysates of
      osteogenically differentiated hMSCs, we showed that CLIC3 interacts with NIMA
      related kinase 9 (NEK9) and phosphatidylserine synthase 1 (PTDSS1) in vitro, and
      this finding was supported by immunofluorescent analysis. In addition, inhibition
      of NEK9 or PTDSS1 gene expression by shRNAs inhibited osteoblast differentiation
      and mineralization. In conclusion, we successfully identified CLIC3 to be a
      lineage-specific gene regulating osteoblast differentiation and bone formation
      through its interaction with NEK9 and PTDSS1. (c) The Authors. JBMR Plus is
      published by Wiley Periodicals, Inc. on behalf of the American Society for Bone
      and Mineral Research.

PMID- 30283879
TI  - Influence of Dosing Interval and Administration on the Bone Metabolism, Skeletal
      Effects, and Clinical Efficacy of Parathyroid Hormone in Treating Osteoporosis: A
      Narrative Review.
AB  - Recombinant human parathyroid hormone (PTH) is the key anabolic agent used for
      preventing fracture in postmenopausal women with osteoporosis. In bone
      metabolism, PTH signaling is mediated through a G protein-coupled receptor that
      affects various post-receptor signaling pathways. Results of preclinical and
      clinical studies have shown that PTH improves both the structure and strength of
      bone tissue. Once daily subcutaneous injection of the PTH fragment, teriparatide
      (PTH [1-34]), is the most commonly recommended formulation and dosing strategy in
      clinical practice. However, other dosing intervals, formulations, and routes have
      been investigated in preclinical and clinical studies. In particular, once-weekly
      and cyclical administration have been investigated mainly as a means of reducing
      the high direct costs of treatment. In preclinical studies, bone
      formation/resorption markers, bone mineral density measurements, and
      histomorphometric parameters improved with both once-daily and once-weekly
      administration. However, the magnitude and duration of such improvements were
      generally greater with once-daily PTH administration. In clinical studies,
      reductions in fracture incidence were also noted with both once-daily and once
      weekly PTH administration, although improvements in nonvertebral fractures are
      less evident with once-weekly administration. This narrative review details the
      differences between PTH formulation and dosing strategies in relation to
      preclinical and clinical efficacy/safety parameters, although it should be
      stressed that no head-to-head studies allow direct comparisons. This review also
      seeks to outline practical considerations involved with PTH prescribing and new
      directions in research regarding routes of administration. (c) 2017 The Authors.
      JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American
      Society for Bone and Mineral Research.

PMID- 30283880
TI  - The CRH-Transgenic Cushingoid Mouse Is a Model of Glucocorticoid-Induced
      Osteoporosis.
AB  - Glucocorticoids (GCs) have unparalleled anti-inflammatory and immunosuppressive
      properties, which accounts for their widespread prescription and use.
      Unfortunately, a limitation to GC therapy is a wide range of negative side
      effects including Cushing's syndrome, a disease characterized by metabolic
      abnormalities including muscle wasting and osteoporosis. GC-induced osteoporosis
      occurs in 30% to 50% of patients on GC therapy and thus, represents an important
      area of study. Herein, we characterize the molecular and physiologic effects of
      GC-induced osteoporosis using the Cushing's mouse model, the corticotropin
      releasing hormone (CRH) transgenic mouse (CRH-Tg). The humeri, femurs, and tibias
      from wild-type (WT) and CRH-Tg male mice, aged 13 to 14 weeks old were subjected
      to multiple bone tests including, micro-computed tomography (MUCT), static and
      dynamic histomorphometry, strength testing, and gene expression analyses. The CRH
      Tg mice had a 38% decrease in cortical bone area, a 35% decrease in cortical
      thickness, a 16% decrease in trabecular thickness, a sixfold increase in bone
      adiposity, a 27% reduction in osteoid width, a 75% increase in bone-resorbing
      osteoclast number/bone surface, a 34% decrease in bone formation rate, and a 40%
      decrease in bone strength compared to WT mice. At the gene expression level, CRH
      Tg bone showed significantly increased osteoclast markers and decreased
      osteoblast markers, whereas CRH-Tg muscle had increased muscle atrophy gene
      markers compared to WT mice. Overall, the CRH-Tg mouse model aged to 14 weeks
      recapitulated many features of osteoporosis in Cushing's syndrome and thus,
      represents a useful model to study GC-induced osteoporosis and interventions that
      target the effects of GCs on the skeleton. (c) 2017 The Authors. JBMR Plus is
      published by Wiley Periodicals, Inc. on behalf of the American Society for Bone
      and Mineral Research.

PMID- 30283881
TI  - Interactions of Phosphate Metabolism With Serious Injury, Including Burns.
AB  - Approximately 85% of the body's phosphate pool resides within the skeleton. The
      remaining 15% is stored as high-energy phosphates or in its free form, where it
      acts as a substrate for adenosine triphosphate (ATP) production. Accordingly,
      phosphate plays a crucial role in energy metabolism. Trauma and critical illness
      result in a hypermetabolic state in which energy expenditure increases. The
      impact of trauma and critical illness on the body's phosphate stores and
      phosphate-dependent metabolic reactions is poorly understood. We had previously
      observed that after severe burn trauma, increased energy expenditure is
      temporally related to a marked reduction in serum concentrations of both
      parathyroid hormone and fibroblast growth factor 23, both of which have
      phosphaturic effects. The aim of this article is to describe as far as is known
      the similarities and differences in phosphate metabolism in different types of
      injury and to infer what these differences tell us about possible signaling
      pathways that may link increased phosphate utilization and phosphate retention.
      (c) 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf
      of the American Society for Bone and Mineral Research.

PMID- 30283882
TI  - Treatment With a Soluble Bone Morphogenetic Protein Type 1A Receptor (BMPR1A)
      Fusion Protein Increases Bone Mass and Bone Formation in Mice Subjected to
      Hindlimb Unloading.
AB  - Previous work has shown that the soluble murine BMPR1A-fusion protein (mBMPR1A
      mFc) binds to BMP2 and BMP4 with high affinity, preventing downstream signaling.
      Further, treatment of intact and ovariectomized mice with mBMPR1A-mFc leads to
      increased bone mass, and improved bone microarchitecture and strength, via
      increased bone formation and reduced resorption. In this study, we tested the
      effects of mBMPR1A-mFc on disuse-induced bone loss caused by 21 days of hindlimb
      unloading (HLU) via tail suspension versus cage controls (CONs). Adult female
      C57BL/6J mice (12 weeks old) were assigned to one of four groups (n = 10 each):
      CON-VEH; CON-mBMPR1A-mFc; HLU-VEH; and HLU-mBMPR1A-mFc. Mice were injected
      subcutaneously with VEH or mBMPR1A-mFc (4.5 mg/kg, 2*/week). Leg BMD declined in
      the HLU-VEH group (-5.3% +/- 1.3%), whereas it was unchanged in HLU-mBMPR1A-mFc (
      0.3% +/- 0.9%, p < 0.05 versus HLU-VEH). Leg BMD increased significantly more in
      CON-mBMPR1A-mFc than CON-VEH (10.2% +/- 0.6% versus 4.4% +/- 0.8%). In the femur,
      trabecular, and cortical bone microarchitecture was worse in the HLU-VEH compared
      to CON-VEH mice, whereas mBMPR1A-mFc treatment for 3 weeks led to greater
      Tb.BV/TV, Tb.Th, and midshaft Ct.Th in both the HLU and CON groups compared to
      comparable VEH-treated counterparts (p < 0.05). HLU-mBMPR1A-mFc mice also had 21%
      greater failure load (p < 0.05) compared to their VEH-treated counterparts.
      Dynamic histomorphometry indicated that treatment with mBMPR1A-mFc led to
      significantly greater mineralizing surface and mineral apposition rate, resulting
      in a 3.5-fold and fivefold higher bone formation rate in the mBMPR1A-mFc-treated
      CON and HLU animals versus VEH groups, respectively. mBMPR1A-mFc-treated mice had
      a similar osteoblast surface but significantly lower osteoclast surface than VEH
      treated animals in both the CON and HLU groups. Altogether, these findings
      suggest that treatment with the soluble BMPR1A fusion protein may be useful for
      maintenance of skeletal integrity in the setting of disuse-induced bone loss.

PMID- 30283883
TI  - Improvement of Giant Cell Lesions of the Jaw Treated With High and Low Doses of
      Denosumab: A Case Series.
AB  - Giant cell tumors (GCTs) and central giant cell granulomas (CGCGs) are aggressive
      lesions that appear in the jaw. These lesions occur in the second and third
      decades of life and often arise in the mandible. Clinical manifestations of these
      lesions vary from asymptomatic to symptomatic tooth displacement with cortical
      perforation. GCTs, which are characterized by multinucleated osteoclast-type
      giant cells that express receptor activator of nuclear factor-kappaB (RANK)
      ligand, rarely present in the jaw and have overlapping histopathologic features
      with CGCGs, which are composed of fibroblastic stromal cell lesions. GCTs and
      CGCGs have overlying histopathologic features that make distinction between the
      two challenging. There is a real controversy as to whether giant cell tumors and
      central giant cell granulomas are in fact, one and the same lesion. The majority
      of GCTs occur in the long bone, with surgery being the typical therapeutic
      option. Denosumab as a treatment modality is a fairly new concept that has been
      used effectively in GCTs affecting long bones. There is less experience, however,
      with its use for jaw lesions. This seven-case series describes the effective use
      of both low-dose and high-dose denosumab in the treatment of GCTs and CGCGs
      affecting the jaw and special dosing considerations for younger patients who
      present with disease. (c) 2017 The Authors. JBMR Plus Published by Wiley
      Periodicals, Inc. on behalf of the American Society for Bone and Mineral
      Research.

PMID- 30283884
TI  - Is Retinal Microvascular Abnormalities an Independent Risk Factor of Vertebral
      Fractures? A Prospective Study From a Chinese Population.
AB  - Low bone mineral density (BMD) and microvascular diseases (MVD) share various
      common risk factors; however, whether MVD is an independent risk factor of
      vertebral fractures is incompletely understood. The aim of this study is to
      clarify whether MVD is an independent risk factor of vertebral fractures. In this
      prospective study, calcaneal BMD and retinal microvascular abnormalities were
      assessed at baseline from June 2011 to January 2012. A total of 2176
      premenopausal women, 2633 postmenopausal women, 2998 men aged <65 years, and 737
      men aged >=65 were included. Then with/without retinal microvascular
      abnormalities cohorts were followed for an average of 2.93 years to find out the
      relationship between MVD and vertebral fractures. At the baseline, after full
      adjustment, retinal microvascular abnormalities were related to risk of low BMD
      only in men aged >=65 years (odds ratio [OR] = 2.506; 95% confidence interval
      [CI] 1.454-4.321; p = 0.001). After follow-up of 2.93 years, retinal
      microvascular abnormalities were related to risk of vertebral fractures in men
      aged >=65 years (OR = 2.475; 95% CI 1.085-5.646; p = 0.031) when adjustment for
      confounding factors. However, no associations were found between MVD and
      vertebral fractures in men aged <65 years, premenopausal women, and
      postmenopausal women. When stratified by diabetes, in the without-diabetes group,
      the men with retinal microvascular abnormalities had higher risk for vertebral
      fractures than without retinopathy (OR = 2.194; 95% CI 1.097-4.389; p = 0.026);
      however, the difference was not found in women. In the diabetes group, there were
      no significant differences of risk for vertebral fractures between those with
      retinal microvascular abnormalities and those without both in men and women.
      Stratified by hypertension, the men with retinopathy had higher risk for
      vertebral fractures than those without among the hypertension group (OR = 2.034;
      95% CI 1.163-3.559; p = 0.013), but a difference was not found among women. In
      the without-hypertension group, no relation was found between MVD and fracture
      both in men and women. In conclusion, MVD is an independent risk factor of
      vertebral fractures in old men. (c) 2017 The Authors. JBMR Plus is published by
      Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral
      Research.

PMID- 30283885
TI  - Insulin-Stimulated Bone Blood Flow and Bone Biomechanical Properties Are
      Compromised in Obese, Type 2 Diabetic OLETF Rats.
AB  - Type 2 diabetes (T2D) increases skeletal fragility and fracture risk; however,
      the underlying mechanisms remain to be identified. Impaired bone vascular
      function, in particular insulin-stimulated vasodilation and blood flow is a
      potential, yet unexplored mechanism. The purpose of this study was to determine
      the effects of T2D on femoral biomechanical properties, trabecular
      microarchitecture, and insulin-stimulated bone vasodilation by comparison of
      hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats with normoglycemic
      control OLETF rats. Four-week old, male OLETF rats were randomized to two groups:
      type 2 diabetes (O-T2D) or normoglycemic control (O-CON). O-T2D were allowed ad
      libitum access to a rodent chow diet and O-CON underwent moderate caloric
      restriction (30% restriction relative to intake of O-T2D) to maintain normal body
      weight (BW) and glycemia until 40 weeks of age. Hyperphagic O-T2D rats had
      significantly greater BW, body fat, and blood glucose than O-CON. Total cross
      sectional area (Tt.Ar), cortical area (Ct.Ar), Ct.Ar/Tt.Ar, and polar moment of
      inertia of the mid-diaphyseal femur adjusted for BW were greater in O-T2D rats
      versus O-CON. Whole-bone biomechanical properties of the femur assessed by
      torsional loading to failure did not differ between O-T2D and O-CON, but tissue
      level strength and stiffness adjusted for BW were reduced in O-T2D relative to O
      CON. Micro-computed tomography (MUCT) of the distal epiphysis showed that O-T2D
      rats had reduced percent bone volume, trabecular number, and connectivity
      density, and greater trabecular spacing compared with O-CON. Basal tibial blood
      flow assessed by microsphere infusion was similar in O-T2D and O-CON, but the
      blood flow response to insulin stimulation in both the proximal epiphysis and
      diaphyseal marrow was lesser in O-T2D compared to O-CON. In summary, impaired
      insulin-stimulated bone blood flow is associated with deleterious changes in bone
      trabecular microarchitecture and cortical biomechanical properties in T2D,
      suggesting that vascular dysfunction might play a causal role in diabetic bone
      fragility. (c) 2017 The Authors. JBMR Plus Published by Wiley Periodicals, Inc.
      on behalf of the American Society for Bone and Mineral Research.

PMID- 30283886
TI  - Genetic Risk Factors for Atypical Femoral Fractures (AFFs): A Systematic Review.
AB  - Atypical femoral fractures (AFFs) are uncommon and have been associated
      particularly with long-term antiresorptive therapy, including bisphosphonates.
      Although the pathogenesis of AFFs is unknown, their identification in
      bisphosphonate-naive individuals and in monogenetic bone disorders has led to the
      hypothesis that genetic factors predispose to AFF. Our aim was to review and
      summarize the evidence for genetic factors in individuals with AFF. We conducted
      structured literature searches and hand-searching of conference
      abstracts/reference lists for key words relating to AFF and identified 2566
      citations. Two individuals independently reviewed citations for (i) cases of AFF
      in monogenetic bone diseases and (ii) genetic studies in individuals with AFF.
      AFFs were reported in 23 individuals with the following 7 monogenetic bone
      disorders (gene): osteogenesis imperfecta (COL1A1/COL1A2), pycnodysostosis
      (CTSK), hypophosphatasia (ALPL), X-linked osteoporosis (PLS3), osteopetrosis, X
      linked hypophosphatemia (PHEX), and osteoporosis pseudoglioma syndrome (LRP5). In
      8 cases (35%), the monogenetic bone disorder was uncovered after the AFF
      occurred. Cases of bisphosphonate-naive AFF were reported in pycnodysostosis,
      hypophosphatasia, osteopetrosis, X-linked hypophosphatemia, and osteoporosis
      pseudoglioma syndrome. A pilot study in 13 AFF patients and 268 controls
      identified a greater number of rare variants in AFF cases using exon array
      analysis. A whole-exome sequencing study in 3 sisters with AFFs showed, among 37
      shared genetic variants, a p.Asp188Tyr mutation in the GGPS1 gene in the
      mevalonate pathway, critical to osteoclast function, which is also inhibited by
      bisphosphonates. Two studies completed targeted ALPL gene sequencing, an ALPL
      heterozygous mutation was found in 1 case of a cohort of 11 AFFs, whereas the
      second study comprising 10 AFF cases did not find mutations in ALPL. Targeted
      sequencing of ALPL, COL1A1, COL1A2, and SOX9 genes in 5 cases of AFF identified a
      variant in COL1A2 in 1 case. These findings suggest a genetic susceptibility for
      AFFs. A large multicenter collaborative study of well-phenotyped AFF cases and
      controls is needed to understand the role of genetics in this uncommon condition.

PMID- 30283887
TI  - Primary Osteoporosis in Young Adults: Genetic Basis and Identification of Novel
      Variants in Causal Genes.
AB  - Genetic determinants contribute to osteoporosis and enhance the risk of fracture.
      Genomewide association studies of unselected population-based individuals or
      families have identified polymorphisms in several genes related to low bone
      density, but not in osteoporotic patients with Z-score < -2.0 SD with fragility
      fracture(s). The aim of this study was to determine the causal genes of
      idiopathic osteoporosis in the adulthood. Also, we used next-generation
      sequencing of candidate genes in a cohort of 123 young or middle-aged adults with
      idiopathic osteoporosis. All patients were included if they had a low bone
      mineral density (Z-score < -2 SD), a diagnosis before age 55 years (mean +/- SD,
      48.4 +/- 10.6 years; mean +/- SD age at first fracture, 30.4 +/- 17.4 years) and
      fracture or not. We found that 11 patients carried rare or novel variants in
      COL1A2 (n = 4), PLS3 (n = 2), WNT1 (n = 4), or DKK1 (n = 1). We showed a high
      prevalence of pathogenic variants in LRP5: 22 patients (17.8%) had the
      p.Val667Met variant, including three at the homozygous level and 16 (13%)
      carrying a novel or very rare variant. Functional analysis revealed that the LRP5
      missense variants resulted in reduced luciferase activity, which indicates
      reduced activation of canonical WNT signaling. The clinical phenotype of patients
      carrying causal gene variants was indistinguishable. In conclusion, molecular
      screening of young osteoporotic adults revealed several variants and could be
      useful to characterize susceptibility genes for personalizing treatment, in
      particular for the new anabolic drugs.(c) 2017 The Authors. JBMR Plus is
      published by Wiley Periodicals, Inc. on behalf of the American Society for Bone
      and Mineral Research.

PMID- 30283888
TI  - Parathyroid Hormone Signaling in Osteocytes.
AB  - Osteocytes are the most abundant cell type in bone and play a central role in
      orchestrating skeletal remodeling, in part by producing paracrine-acting factors
      that in turn influence osteoblast and osteoclast activity. Recent evidence has
      indicated that osteocytes are crucial cellular targets of parathyroid hormone
      (PTH). Here, we will review the cellular and molecular mechanisms through which
      PTH influences osteocyte function. Two well-studied PTH target genes in
      osteocytes are SOST and receptor activator of NF-kappaB ligand (RANKL). The
      molecular mechanisms through which PTH regulates expression of these two crucial
      target genes will be discussed. Beyond SOST and RANKL, PTH/PTH-related peptide
      (PTHrP) signaling in osteocytes may directly influence the way osteocytes remodel
      their perilacunar environment to influence bone homeostasis in a cell-autonomous
      manner. Here, I will highlight novel, additional mechanisms used by PTH and PTHrP
      to modulate bone homeostasis through effects in osteocytes. (c) 2017 The Authors.
      JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American
      Society for Bone and Mineral Research.

PMID- 30283889
TI  - Sclerostin Antibody Treatment Stimulates Bone Formation to Normalize Bone Mass in
      Male Down Syndrome Mice.
AB  - Down syndrome (DS), characterized by trisomy of human chromosome 21, is
      associated with a variety of endocrine disorders as well as profound skeletal
      abnormalities. The low bone mass phenotype in DS is defined by low bone turnover
      due to decreased osteoclast and osteoblast activity, decreasing the utility of
      antiresorptive agents in people with DS. Sclerostin antibody (SclAb) is a
      therapeutic candidate currently being evaluated as a bone anabolic agent. Scl,
      the product of the sclerostin gene (SOST), inhibits bone formation through its
      inhibition of Wnt signaling. SclAb increases bone mass by suppressing the action
      of the endogenous inhibitor of bone formation, Scl. To examine the effects of
      SclAb on the DS bone phenotype, 8-week-old male wild-type (WT) andTs65Dn DS mice
      were treated with 4 weekly iv injections of 100 mg/kg SclAb. Dual-energy X-ray
      absorptiometry (DXA), microCT, and dynamic histomorphometry analyses revealed
      that SclAb had a significant anabolic effect on both age-matched WT littermate
      controls and Ts65Dn DS mice that was osteoblast mediated, without significant
      changes in osteoclast parameters. SclAb treatment significantly increased both
      cortical and trabecular bone mass at multiple sites; SclAb treatment resulted in
      the normalization of Ts65Dn bone mineral density (BMD) to WT levels in the
      proximal tibia, distal femur, and whole body. Ex vivo bone marrow cultures
      demonstrated that SclAb increased the recruitment of the mesenchymal progenitors
      into the osteoblast lineage, as indicated by increased alkaline phosphatase
      positive colonies, with no effect on osteoclast differentiation. Together, in the
      setting of a murine model of DS and decreased bone turnover, SclAb had a potent
      anabolic effect. SclAb stimulated bone formation and increased osteoblastogenesis
      without affecting osteoclastogenesis or bone resorption. These data suggest that
      SclAb is a promising new therapy to improve bone mass and reduce fracture risk in
      the face of the low bone mass and turnover prevalent in the DS population.

PMID- 30283890
TI  - Flare-Up After Maxillofacial Surgery in a Patient With Fibrodysplasia Ossificans
      Progressiva: An [18F]-NaF PET/CT Study and a Systematic Review.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder leading to
      progressive heterotopic ossifications (HO) of muscles, tendons, and ligaments,
      which can be induced by trauma or by surgery. Despite strong medical advice to
      the contrary, an FOP patient insisted on surgery to alleviate her complete
      trismus, which caused an unbearable impact on her quality of life (QOL). The
      entire trismus history of this FOP patient is presented. [18F]-NaF position
      emission tomography/computed tomography (PET/CT) scans were introduced as an
      imaging method for heterotopic bone formation activity. To place our findings
      into context, a systematic review on jaw surgery in FOP was performed. After
      falling down the stairs, a 9-year-old patient developed mobility impairment of
      her left-sided jaw. During the following 13 years bone scintigraphy showed
      persistent activity of the disease leading to progressive left-sided zygomatico
      mandibular fusion by HO, resulting in complete trismus. Within 1 month after HO
      removal on the left side and a matching right coronoidectomy, [18F]-NaF PET/CT
      demonstrated a substantial flare-up activity followed by new HO in both masseter
      and temporalis muscles. Despite recurrent HO and trismus her QOL increased due to
      a stable increased interincisal opening of 5.5 mm. Although systematic review
      reveals a 100% risk of HO recurrence after jaw surgery, information on improved
      QOL is scarce. In conclusion, surgery in FOP may be beneficial for QOL despite
      new HO formation. Assessment of disease activity using [18F]-NaF PET/CT is
      possible before HO is evident on CT and may serve as a new and quantitative
      marker of the disease. (c) 2017 The Authors. JBMR Plus Published by Wiley
      Periodicals, Inc. on behalf of the American Society for Bone and Mineral
      Research.

PMID- 30283891
TI  - Broadening Our Horizons: JBMR and JBMR Plus Embrace Preprints.

PMID- 30283892
TI  - Optimizing Sequential and Combined Anabolic and Antiresorptive Osteoporosis
      Therapy.
AB  - As osteoporosis therapy options have expanded, and clinical guidelines have begun
      to embrace the concept of limited treatment courses and "drug holidays," the
      choices that physicians must make when initiating, electing to continue, or
      switching therapies have become more complex. As a result, one of the fundamental
      issues that must be carefully considered is whether, when, and in what sequence
      anabolic therapies should be utilized. This review evaluates the current evidence
      supporting the optimal sequence for the use of anabolic and antiresorptive drugs
      and assesses the expanding number of clinical trials favoring the initial use of
      anabolic therapy followed by an antiresorptive agent. This review also explores
      the evidence suggesting that the effectiveness of anabolic medications are
      diminished when used in patients that have been previously treated with specific
      antiresorptive drugs for prolonged periods. Finally, the recent advances in
      designing combination antiresorptive/anabolic treatment approaches are detailed,
      with a focus on combined denosumab/teriparatide regimens, which appear to provide
      the most substantial and clinically relevant skeletal benefits to patients with
      established osteoporosis. (c) 2018 The Authors. JBMR Plus is published by Wiley
      Periodicals, Inc. on behalf of the American Society for Bone and Mineral
      Research.

PMID- 30283893
TI  - Cytokine Mixtures Mimicking Secretomes From Mesenchymal Stem Cells Improve
      Medication-Related Osteonecrosis of the Jaw in a Rat Model.
AB  - Recently, several studies have demonstrated that intravenous administration of
      mesenchymal stem cells (MSCs) improve medication-related osteonecrosis of the jaw
      (MRONJ), and paracrine effects of secretomes from MSCs have been hypothesized as
      the primary contributors. These secretomes in conditioned media from human MSCs
      (MSC-CM) were previously demonstrated to promote bone and tissue regeneration.
      Because MSC-CM contain cytokines monocyte chemoattractant protein (MCP)-1,
      insulin growth factor (IGF)-1, and vascular endothelial growth factor (VEGF) at
      relatively higher concentrations than other factors, these cytokines were
      considered as relevant active factors for tissue regeneration. By mixing the
      recombinant proteins of MCP-1, IGF-1, and VEGF, included at the same
      concentrations in MSC-CM, we prepared cytokine mixtures mimicking MSC-CM and then
      evaluated its therapeutic effects in a rat MRONJ model. In vitro, cytokine
      mixtures promoted osteogenic differentiation, migration, and proliferation of rat
      MSCs. In addition, these maintained osteoclastic function. In vivo, we used a rat
      MRONJ model to examine therapeutic effects of the cytokine mixtures through
      intravenous administration. In MSC-CM or cytokine mixture group, open alveolar
      sockets in 66% or 67% of the rats with MRONJ, respectively, healed with complete
      soft tissue coverage and socket bones, whereas in the other groups, the exposed
      necrotic bone with inflamed soft tissue remained. Histological analysis revealed
      new bone formation and the appearance of osteoclasts in MSC-CM or cytokine
      mixture group; however, osteoclasts were significantly reduced in the other
      groups. Thus, we concluded that intravenous administration of cytokine mixtures
      might be an effective therapeutic modality for treating patients with MRONJ.

PMID- 30283894
TI  - An Ectopic Imaging Window for Intravital Imaging of Engineered Bone Tissue.
AB  - Tissue engineering is a promising branch of regenerative medicine, but its
      clinical application remains limited because thorough knowledge of the in vivo
      repair processes in these engineered implants is limited. Common techniques to
      study the different phases of bone repair in mice are destructive and thus not
      optimal to gain insight into the dynamics of this process. Instead, multiphoton
      intravital microscopy (MP-IVM) allows visualization of (sub)cellular processes at
      high resolution and frequency over extended periods of time when combined with an
      imaging window that permits optical access to implants in vivo. In this study, we
      have developed and validated an ectopic imaging window that can be placed over a
      tissue-engineered construct implanted in mice. This approach did not interfere
      with the biological processes of bone regeneration taking place in these
      implants, as evidenced by histological and micro-computed tomography (MUCT)-based
      comparison to control ectopic implants. The ectopic imaging window permitted
      tracking of individual cells over several days in vivo. Furthermore, the use of
      fluorescent reporters allowed visualization of the onset of angiogenesis and
      osteogenesis in these constructs. Taken together, this novel imaging window will
      facilitate further analysis of the spatiotemporal regulation of cellular
      processes in bone tissue-engineered implants and provides a powerful tool to
      enhance the therapeutic potential of bone tissue engineering.

PMID- 30283896
TI  - Sharing the Wealth: ASBMR Journals Update Policies on Data Sharing and Data
      Repositories.

PMID- 30283895
TI  - Serum Calcium to Phosphorous (Ca/P) Ratio Is a Simple, Inexpensive, and Accurate
      Tool in the Diagnosis of Primary Hyperparathyroidism.
AB  - Primary hyperparathyroidism (PHPT) diagnosis is challenging and is based on serum
      calcium (Ca) and parathyroid hormone (PTH). Because serum Ca and phosphorous (P)
      are inversely related in PHPT, we investigated the diagnostic value of the serum
      Ca/P ratio in the diagnosis of PHPT. We report a single-center, case-controlled,
      retrospective study including 97 patients with documented PHPT and compared them
      with those of 96 controls (C). The main outcome measures were: serum PTH, 25-OH
      vitamin D, Ca, P, albumin, and creatinine. Sensitivity, specificity, positive
      predictive value, negative predictive value, and accuracy of the serum Ca/P ratio
      were calculated. The results were verified using an independent, anonymous set of
      data extracted from a laboratory database containing over 900 million entries. A
      total of 35 (36.1%) PHPT patients had normocalcemic PHPT (NCHPT). Ca and PTH were
      significantly higher in PHPT than in C (p < 0.0001). P was significantly lower in
      PHPT than in C (p < 0.0001). The Ca/P ratio was significantly higher in PHPT than
      in C (p < 0.0001). Receiver-operating characteristic (ROC) curves analyses
      identified a cutoff of 2.71 (3.5 if Ca and P are expressed in mg/dL) for Ca/P
      ratio with a sensitivity and specificity of 86% and 87%, respectively (p <
      0.0001), confirmed by the independent, big data approach. In conclusion, Ca/P is
      a valuable tool for the diagnosis of PHPT and is of superior value compared to
      serum Ca alone, especially in NCPHT. Because Ca/P is simple, inexpensive, and
      easily accessible worldwide, this ratio is useful for PHPT diagnosis, especially
      in laboratory/medical settings relying on limited resources, such as low-income
      countries. (c) 2017 The Authors. JBMR Plus is published by Wiley Periodicals,
      Inc. on behalf of the American Society for Bone and Mineral Research.

PMID- 30283898
TI  - Early Signs of Bone and Cartilage Changes Induced by Treadmill Exercise in Rats.
AB  - This study aims to investigate the earliest alterations of bone and cartilage
      tissues as a result of different exercise protocols in the knee joint of Wistar
      rats. We hypothesize that pretraining to a continuous intense running protocol
      would protect the animals from cartilage degeneration. Three groups of animals
      were used: (i) an adaptive (pretraining) running group that ran for 8 weeks with
      gradually increasing velocity and time of running followed by a constant running
      program (6 weeks of 1.12 km/hour running per day); (ii) a non-adaptive running
      (constant running) group that initially rested for 8 weeks followed by 6 weeks of
      constant running; and (iii) a non-running (control) group. At weeks 8, 14, and 20
      bone and cartilage were analyzed. Both running groups developed mild symptoms of
      cartilage irregularities, such as chondrocyte hypertrophy and cell clustering in
      different cartilage zones, in particular after the adaptive running protocol. As
      a result of physical training in the adaptive running exercise a dynamic response
      of bone was detected at week 8, where bone growth was enhanced. Conversely, the
      thickness of epiphyseal trabecular and subchondral bone (at week 14) was reduced
      due to the constant running in the period between 8 and 14 weeks. Finally, the
      intermediate differences between the two running groups disappeared after both
      groups had a resting period (from 14 to 20 weeks). The adaptive running group
      showed an increase in aggrecan gene expression and reduction of MMP2 expression
      after the initial 8 weeks running. Thus, the running exercise models in this
      study showed mild bone and cartilage/chondrocyte alterations that can be
      considered as early-stage osteoarthritis. The pretraining adaptive protocol
      before constant intense running did not protect from mild cartilage degeneration.
      (c) 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf
      of American Society for Bone and Mineral Research.

PMID- 30283897
TI  - Bone Health After Bariatric Surgery.
AB  - Bariatric surgery results in long-term weight loss and improvement or resolution
      in obesity-related comorbidities. However, mounting evidence indicates that it
      adversely affects bone health. This review summarizes clinical research findings
      about the impact of bariatric surgery on skeletal outcomes. The literature is the
      largest and strongest for the Roux-en-Y gastric bypass (RYGB) procedure, as RYGB
      was the most commonly performed bariatric procedure worldwide until it was very
      recently overtaken by the sleeve gastrectomy (SG). Because SG is a newer
      procedure, its skeletal effects have not yet been well defined. Epidemiologic
      studies have now demonstrated an increased risk of fracture after RYGB and
      biliopancreatic diversion with duodenal switch, both of which include a
      malabsorptive component. As these epidemiologic data have emerged, patient
      oriented studies have elucidated the bone tissue-level changes that may account
      for the heightened skeletal fragility. Bariatric surgery induces early and
      dramatic increases in biochemical markers of bone turnover. A notable feature of
      recent patient-oriented clinical studies is the application of advanced skeletal
      imaging modalities; studies address the limitations of dual-energy X-ray
      absorptiometry (DXA) by using quantitative computed tomography (QCT)-based
      modalities to examine volumetric bone mineral density and compartment-specific
      density and microstructure. RYGB results in pronounced declines in bone mass at
      the axial skeleton demonstrated by DXA and QCT, as well as at the appendicular
      skeleton demonstrated by high-resolution peripheral quantitative computed
      tomography (HR-pQCT). RYGB has detrimental effects on trabecular and cortical
      microarchitecture and estimated bone strength. Skeletal changes after RYGB appear
      early and continue even after weight loss plateaus and weight stabilizes. The
      skeletal effects of bariatric surgery are presumably multifactorial, and
      mechanisms may involve nutritional factors, mechanical unloading, hormonal
      factors, and changes in body composition and bone marrow fat. Clinical guidelines
      address bone health and may mitigate the negative skeletal effects of surgery,
      although more research is needed to direct and support such guidelines. (c) 2018
      The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of
      American Society for Bone and Mineral Research.

PMID- 30283899
TI  - Differential Adaptive Response of Growing Bones From Two Female Inbred Mouse
      Strains to Voluntary Cage-Wheel Running.
AB  - The phenotypic response of bones differing in morphological, compositional, and
      mechanical traits to an increase in loading during growth is not well understood.
      We tested whether bones of two inbred mouse strains that assemble differing sets
      of traits to achieve mechanical homeostasis at adulthood would show divergent
      responses to voluntary cage-wheel running. Female A/J and C57BL6/J (B6) 4-week
      old mice were provided unrestricted access to a standard cage-wheel for 4 weeks.
      A/J mice have narrow and highly mineralized femora and B6 mice have wide and less
      mineralized femora. Both strains averaged 2 to 9.5 km of running per day, with
      the average-distance run between strains not significantly different (p = 0.133).
      Exercised A/J femora showed an anabolic response to exercise with the diaphyses
      showing a 2.8% greater total area (Tt.Ar, p = 0.06) and 4.7% greater cortical
      area (Ct.Ar, p = 0.012) compared to controls. In contrast, exercised B6 femora
      showed a 6.2% (p < 0.001) decrease in Tt.Ar (p < 0.001) and a 6.7% decrease in
      Ct.Ar (p = 0.133) compared to controls, with the femora showing significant
      marrow infilling (p = 0.002). These divergent morphological responses to
      exercise, which did not depend on the daily distance run, translated to a 7.9% (p
      = 0.001) higher maximum load (ML) for exercised A/J femora but no change in ML
      for exercised B6 femora compared to controls. A consistent response was observed
      for the humeri but not the vertebral bodies. This differential outcome to
      exercise has not been previously observed in isolated loading or forced treadmill
      running regimes. Our findings suggest there are critical factors involved in the
      metabolic response to exercise during growth that require further consideration
      to understand how genotype, exercise, bone morphology, and whole-bone strength
      interact during growth. (c) 2018 The Authors. JBMR Plus is published by Wiley
      Periodicals, Inc. on behalf of the American Society for Bone and Mineral
      Research.

PMID- 30283900
TI  - An N-Ethyl-N-Nitrosourea (ENU) Mutagenized Mouse Model for Autosomal Dominant
      Nonsyndromic Kyphoscoliosis Due to Vertebral Fusion.
AB  - Kyphosis and scoliosis are common spinal disorders that occur as part of complex
      syndromes or as nonsyndromic, idiopathic diseases. Familial and twin studies
      implicate genetic involvement, although the causative genes for idiopathic
      kyphoscoliosis remain to be identified. To facilitate these studies, we
      investigated progeny of mice treated with the chemical mutagen N-ethyl-N
      nitrosourea (ENU) and assessed them for morphological and radiographic
      abnormalities. This identified a mouse with kyphoscoliosis due to fused lumbar
      vertebrae, which was inherited as an autosomal dominant trait; the phenotype was
      designated as hereditary vertebral fusion (HVF) and the locus as Hvf. Micro
      computed tomography (MUCT) analysis confirmed the occurrence of nonsyndromic
      kyphoscoliosis due to fusion of lumbar vertebrae in HVF mice, consistent with a
      pattern of blocked vertebrae due to failure of segmentation. MUCT scans also
      showed the lumbar vertebral column of HVF mice to have generalized disc
      narrowing, displacement with compression of the neural spine, and distorted
      transverse processes. Histology of lumbar vertebrae revealed HVF mice to have
      irregularly shaped vertebral bodies and displacement of intervertebral discs and
      ossification centers. Genetic mapping using a panel of single nucleotide
      polymorphic (SNP) loci arranged in chromosome sets and DNA samples from 23 HVF
      (eight males and 15 females) mice, localized Hvf to chromosome 4A3 and within a 5
      megabase (Mb) region containing nine protein coding genes, two processed
      transcripts, three microRNAs, five small nuclear RNAs, three large intergenic
      noncoding RNAs, and 24 pseudogenes. However, genome sequence analysis in this
      interval did not identify any abnormalities in the coding exons, or exon-intron
      boundaries of any of these genes. Thus, our studies have established a mouse
      model for a monogenic form of nonsyndromic kyphoscoliosis due to fusion of lumbar
      vertebrae, and further identification of the underlying genetic defect will help
      elucidate the molecular mechanisms involved in kyphoscoliosis. (c) 2018 The
      Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the
      American Society for Bone and Mineral Research.

PMID- 30283901
TI  - The Interaction of BMP2-Induced Defect Healing in Rat and Fixator Stiffness
      Modulates Matrix Alignment and Contraction.
AB  - Successful fracture healing requires a tight interplay between mechanical and
      biological cues. In vitro studies illustrated that mechanical loading modulates
      bone morphogenetic protein (BMP) signaling. However, in the early phases of large
      bone defect regeneration in vivo, the underlying mechanisms leading to this
      mechanosensation remained unknown. We investigated the interaction of BMP2
      stimulation and mechanical boundary conditions in a rat critical-sized femoral
      defect model (5 mm) stabilized with three distinctly different external fixator
      stiffness. Defects were treated with 5 MUg rhBMP2 loaded on an absorbable
      collagen sponge. Early matrix alignment was monitored by second-harmonic
      generation imaging. Bony bridging of defects and successive healing was monitored
      by histology at day 7 and day 14 as well as in vivo microCT at days 10, 21, and
      42 post-operation. Femora harvested at day 42 were characterized mechanically
      assessing torsional load to failure ex vivo. At tissue level, differences between
      groups were visible at day 14 with manifest bone formation in the microCT.
      Histologically, we observed prolonged chondrogenesis upon flexible fixation,
      whereas osteogenesis started earlier after rigid and semirigid fixation. At later
      time points, there was a boost of bone tissue formation upon flexible fixation,
      whereas other groups already displayed signs of tissue maturation. Based on gene
      expression profiling, we analyzed the mechanobiological interplay. Already at day
      3, these analyses revealed differences in expression pattern, specifically of
      genes involved in extracellular matrix formation. Gene regulation correlating
      with fixator stiffness was pronounced at day 7 comprising genes related to
      immunological processes and cellular contraction. The influence of loading on
      matrix contraction was further investigated and confirmed in a 3D bioreactor.
      Taken together, we demonstrate an early onset of mechanical conditions
      influencing BMP2-induced defect healing and shed light on gene regulatory
      networks associated with extracellular matrix organization and contraction that
      seemed to directly impact healing outcomes. (c) 2018 The Authors. JBMR Plus is
      published by Wiley Periodicals, Inc. on behalf of the American Society for Bone
      and Mineral Research.

PMID- 30283902
TI  - The Challenges and Opportunities of Pharmacoepidemiology in Bone Diseases.
AB  - Pharmacoepidemiology is used extensively in osteoporosis research and involves
      the study of the use and effects of drugs in large numbers of people. Randomized
      controlled trials are considered the gold standard in assessing treatment
      efficacy and safety. However, their results can have limited external validity
      when applied to day-to-day patients. Pharmacoepidemiological studies aim to
      assess the effect/s of treatments in actual practice conditions, but they are
      limited by the quality, completeness, and inherent bias due to confounding.
      Sources of information include prospectively collected (primary) as well as
      readily available routinely collected (secondary) (eg, electronic medical
      records, administrative/claims databases) data. Although the former enable the
      collection of ad hoc measurements, the latter provide a unique opportunity for
      the study of large representative populations and for the assessment of rare
      events at relatively low cost. Observational cohort and case-control studies, the
      most commonly implemented study designs in pharmacoepidemiology, each have their
      strengths and limitations. However, the choice of the study design depends on the
      research question that needs to be answered. Despite the many advantages of
      observational studies, they also have limitations. First, missing data is a
      common issue in routine data, frequently dealt with using multiple imputation.
      Second, confounding by indication arises because of the lack of randomization;
      multivariable regression and more specific techniques such as propensity scores
      (adjustment, matching, stratification, trimming, or weighting) are used to
      minimize such biases. In addition, immortal time bias (time period during which a
      subject is artefactually event-free by study design) and time-varying confounding
      (patient characteristics changing over time) are other types of biases usually
      accounted for using time-dependent modeling. Finally, residual "uncontrolled"
      confounding is difficult to assess, and hence to account for it, sensitivity
      analyses and specific methods (eg, instrumental variables) should be considered.

PMID- 30283903
TI  - Semiquantitative Evaluation of Muscle Repair by Diffusion Tensor Imaging in Mice.
AB  - Muscle injury is one of the most common traumas in orthopedic and sports
      medicine. However, there are only a few treatment options with marginal clinical
      benefits for this condition. Muscle repair after injury involves multiple and
      complex processes, such as the inflammation phase, regeneration phase, and
      remodeling phase. To develop a treatment modality and to examine the efficacy of
      novel interventions and agents for patients with muscle injuries, it is essential
      to establish a reliable and sensitive method to monitor the changes in muscle
      structure and status during muscle repair. Diffusion-weighted magnetic resonance
      imaging has been widely used to assess the diffusivity of water molecules in
      tissue. When it is used in combination with diffusion tensor imaging (DTI), the
      microstructure of muscle tissue can be indirectly depicted. In the present study,
      we evaluated the time-course changes in the diffusivity and anisotropy in muscles
      by DTI and histology after injury in mice. We found that the diffusivity and
      anisotropy exhibit distinct kinetics during muscle repair and that these kinetics
      were significantly altered in mutant mice with a defect in muscle regeneration.
      Our data show that muscle repair processes can be readily evaluated and monitored
      by DTI technique and suggest that DTI can be clinically applied for assessing
      muscle injury and repair in humans. (c) 2018 The Authors. JBMR Plus is published
      by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral
      Research.

PMID- 30283904
TI  - Whole-Exome Sequencing Identifies an Intronic Cryptic Splice Site in SERPINF1
      Causing Osteogenesis Imperfecta Type VI.
AB  - The heritable disorder osteogenesis imperfecta (OI) is characterized by bone
      fragility and low bone mass. OI type VI is an autosomal recessive form of the
      disorder with moderate to severe bone fragility. OI type VI is caused by
      mutations in the serpin peptidase inhibitor, clade F, member 1 (SERPINF1), the
      gene coding for pigment epithelium-derived factor (PEDF). Here, we report a
      patient with OI type VI caused by a novel homozygous intronic variant in SERPINF1
      identified by whole-exome sequencing (WES). The mutation was not identified using
      a low bone mass gene panel based on next-generation sequencing. This variant
      creates a novel consensus splice donor site (AGGC to AGGT) in intron 4. Analysis
      of cDNA generated from fibroblasts revealed retention of a 32-bp intronic
      fragment between exons 4 and 5 in the cDNA, a result of alternative splicing from
      the novel splice-donor site. As a result, the aberrant insertion of this intronic
      fragment generated a frameshift pathogenic variant and induced nonsense-mediated
      decay. Furthermore, gene expression by quantitative PCR showed SERPINF1
      expression was dramatically reduced in patient fibroblasts, and PEDF level was
      also significantly reduced in the patient's plasma. In conclusion, we report a
      novel homozygous variant that generates an alternative splice-donor in intron 4
      of SERPINF1 which gives rise to severe bone fragility. The work also demonstrates
      clinical utility of WES analysis, and consideration of noncoding variants, in the
      diagnostic setting of rare bone diseases. (c) 2018 The Authors. JBMR Plus is
      published by Wiley Periodicals, Inc. on behalf of American Society for Bone and
      Mineral Research.

PMID- 30283905
TI  - Sixty-Two-Year-Old Male Suffering From Uremic Leontiasis Ossea Caused by Severe
      Secondary Hyperparathyroidism.
AB  - Secondary hyperparathyroidism (SHPT) is a long-term complication of chronic
      kidney disease-mineral and bone disorder (CKD-MBD). SHPT is characterized by
      hyperplasia of the parathyroid glands and abnormal secretion of parathyroid
      hormones (PTH), calcium and phosphorous metabolic disorders, renal
      osteodystrophy, vascular and soft tissue calcification, malnutrition, and other
      multiple system complications, which can seriously affect the quality of life of
      the patient and increase the risk of cardiovascular disease and mortality rate.
      Uremic leontiasis ossea (ULO) is a medical condition only rarely encountered
      clinically. SHPT causes craniofacial bone deformity accompanied by lesions of the
      nerve, cardiovascular, respiratory, bone, or other systems within the body. The
      case discussed here is related to severe SHPT. A 62-year-old male patient was
      suffering from leontiasis ossea, pectus excavatum, vascular calcification,
      spontaneous bone fractures, and lower limb deformities. He was undergoing
      hemodialysis and given total parathyroidectomy (TPTX) with autotransplantation
      (AT). We further analyzed the multivariate therapeutic effects of TPTX on this
      patient in order to provide clinical data for standardized treatment of
      individuals with CKD-MBD.

PMID- 30283907
TI  - Molecular Phenotyping of Telomerized Human Bone Marrow Skeletal Stem Cells
      Reveals a Genetic Program of Enhanced Proliferation and Maintenance of
      Differentiation Responses.
AB  - Long-term in vitro expansion of bone marrow stromal (skeletal) stem cells (also
      known as human mesenchymal stem cells [hMSC]) is associated with replicative
      senescence and impaired functions. We have previously reported that
      telomerization of hMSC through hTERT overexpression led to bypassing a
      replicative senescence phenotype and improved in vitro and in vivo functions.
      However, the molecular consequence of telomerization is poorly characterized.
      Thus, we compared the molecular phenotype of a well-studied telomerized hMSC
      (hMSC-TERT) cell line with primary hMSC. At a cellular level, both cell
      populations exhibited strong concordance for the known hMSC CD markers, similar
      responses to osteoblast (OB) differentiation induction, and formed heterotopic
      bone in vivo. Overall gene expression was highly correlated between both cell
      types with an average Pearson's correlation coefficient (R2) between the gene
      expression of all primary hMSC and all hMSC-TERT samples of 0.95 (range 0.93
      0.96). Quantitative analysis of gene expression of CD markers, OB cell markers,
      and transcription factors (TF) showed a high degree of similarity between the two
      cell populations (72%, 77%, and 81%, respectively). The hMSC-TERT population was
      enriched mainly for genes associated with cell cycle and cell cycle signaling
      when compared with primary hMSC. Other enrichment was observed for genes involved
      in cell adhesion and skeletal system development and immune response pathways.
      Interestingly, hMSC-TERT shared a telomerization signature with upregulation of
      cancer/testis antigens, MAGE, and PAGE genes. Our data demonstrate that the
      enhanced biological characteristics of hMSC after telomerization are mainly due
      to enhanced expression of cell proliferation genes, whereas gene expression
      responses to differentiation are maintained. (c) 2018 The Authors. JBMR Plus
      Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone
      and Mineral Research.

PMID- 30283906
TI  - The Hidden Burden of Fractures in People Living With HIV.
AB  - The survival of people living with human immunodeficiency virus (HIV) has
      increased markedly since the advent of antiretroviral therapy (ART). However,
      other morbidities have emerged, including osteoporosis. The estimated incidence
      of fractures at any site in people living with HIV ranges from 0.1 per 1000
      person-years to 8.4 per 1000 person-years: at least twice that of people without
      HIV. This increased risk seems to be related to HIV itself and its treatment.
      Risk factors for bone disease in HIV-positive (HIV+) subjects include both
      classical risk factors for osteoporosis and fracture and factors linked to HIV
      itself, such as inflammation, reconstitution syndrome, low CD4, ART, and co
      infection with hepatitis B and C viruses. The risk of fractures in these
      individuals can be at least partially assessed by measurement of BMD and the
      Fracture Risk Assessment Tool (FRAXTM). Only alendronate and zoledronic acid have
      been studied in HIV+ individuals; both show beneficial effects on BMD, although
      data on fracture reduction are not available. (c) 2018 The Authors. JBMR Plus
      Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and
      Mineral Research.

PMID- 30283908
TI  - How Is Adolescent Bone Mass and Density Influenced by Early Life Body Size and
      Growth? The Tromso Study: Fit Futures-A Longitudinal Cohort Study From Norway.
AB  - The effect of birth weight and childhood body mass index (BMI) on adolescents'
      bone parameters is not established. The aim of this longitudinal, population
      based study was to investigate the association of birth weight, childhood BMI,
      and growth, with adolescent bone mass and bone density in a sample of 633
      adolescents (48% girls) from The Tromso Study: Fit Futures. This population-based
      cohort study was conducted in 2010-2011 and 2012-2013 in Tromso, Norway. Bone
      mineral content (BMC) and areal BMD (aBMD) were measured at total hip (TH) and
      total body (TB) by dual-energy X-ray absorptiometry (DXA) and converted to
      internal Z-scores. Birth weight and childhood anthropometric measurements were
      retrospectively obtained from the Medical Birth Registry of Norway and childhood
      health records. Associations between birth weight, BMI, and growth were evaluated
      by fitting linear mixed models with repeated measures of BMC and aBMD at ages 15
      to 17 and 18 to 20 years as the outcome. In crude analysis, a significant
      positive association (p < 0.05) with TB BMC was observed per 1 SD score increase
      in birth weight, observed in both sexes. Higher rate of length growth,
      conditioned on earlier size, from birth to age 2.5 years, and higher rate of
      weight gain from ages 6.0 to 16.5 years, conditioned on earlier size and
      concurrent height growth, revealed stronger associations with bone accrual at
      ages 15 to 20 years compared with other ages. Compared with being normal weight,
      overweight/obesity at age 16.5 years was associated with higher aBMD Z-scores:
      beta coefficient (95% confidence interval [CI]) of 0.78 (0.53, 1.03) and 1.08
      (0.85, 1.31) in girls, 0.63 (0.42, 0.85) and 0.74 (0.54, 0.95) in boys at TH and
      TB, respectively. Similar associations were found for BMC. Being underweight was
      consistently negatively associated with bone parameters in adolescence. In
      conclusion, birth weight influences adolescent bone mass but less than later
      growth and BMI in childhood and adolescence. (c) 2018 The Authors. JBMR Plus
      Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone
      and Mineral Research.

PMID- 30283909
TI  - Compromised Activation of Vitamin D After Elective Surgery: A Prospective Pilot
      Study.
AB  - Surgical stress reduces concentrations of most proteins in serum and necessitates
      a rapid adjustment of hormones dependent on protein binding. Activation of
      vitamin D by renal 1alpha-hydroxylation is dependent on protein binding because
      1,25-dihydroxyvitamin D (1,25(OH)2D3) is formed after megalin-mediated
      reabsorption of 25-hydroxyvitamin D (25OHD) bound to vitamin D binding protein
      (DBP). Postoperative alterations in serum concentrations of DBP and albumin may
      therefore impair 1,25(OH)2D3 production. Our objective was to determine sex
      specific changes in serum concentrations of vitamin D metabolites and sex
      steroids 2, 6, 24, and 48 hours and 3 weeks postoperatively. Fourteen women and
      eleven men aged 45 to 77 years without severe comorbidities undergoing unilateral
      total knee arthroplasty participated in this prospective study in a tertiary
      center for arthroplasty (trial ID: NCT02336932). The main outcome measures were
      total and free serum concentrations of 25OHD, 1,25(OH)2D3, 24,25-dihydroxyvitamin
      D, DBP, albumin, sex hormone binding globulin (SHBG), calcium, and parathyroid
      hormone (PTH). Serum albumin and SHBG decreased postoperatively (Deltaalbumin48h 
      18% [-22%; -14%]). Unexpectedly, concentrations of DBP and 25OHD remained
      unaltered, but 1,25(OH)2D3 declined postoperatively. 1,25(OH)2D3 was 3 weeks
      after surgery -24% (-40%; -8%) lower than preoperative levels, whereas 24,25
      dihydroxyvitamin-D remained unchanged in postmenopausal women. The calculated
      conversion rate of 25OHD to 1,25(OH)2D3 was strongly associated with serum 25-OHD
      and PTH preoperatively, whereas serum calcium was most predictive
      postoperatively. In conclusion, surgery had no effect on serum concentrations of
      DBP, 25OHD, and PTH, whereas production of 1,25(OH)2D3 was markedly reduced.
      Further studies are needed to determine duration and putative outcome effects of
      this postoperative 1,25(OH)2D3 deficit in women, which in part may be due to
      discordance in CYP27B1 and CYP24A1 activity.

PMID- 30283910
TI  - Efficacy of Switching From Teriparatide to Bisphosphonate or Denosumab: A
      Prospective, Randomized, Open-Label Trial.
AB  - There is no consensus on an optimal treatment after daily teriparatide (TPTD). We
      performed a prospective, randomized, open-label, 12-month trial to investigate
      the efficacy of follow-up treatment after daily TPTD treatment for Japanese
      patients. Three-hundred patients were enrolled in this study. Patients received
      oral bisphosphonate (BP) including alendronate (ALN; 35 mg/week) and minodoronate
      (MINO; 50 mg/month), or subcutaneous denosumab (60 mg/6 month). The primary
      efficacy measure was bone mineral density (BMD) responses in the lumbar spine
      (LS) and femoral neck (FN). Lumbar spine BMD increased by 1.3 +/- 5.1% in the ALN
      subgroups, 0.5 +/- 4.6% in the MINO subgroups, and 4.3 +/- 3.5% in the denosumab
      subgroups. Femoral neck BMD increased by 0.7 +/- 4.6% in the ALN subgroups, 0.2
      +/- 4.6% in the MINO subgroups, and 1.4 +/- 3.4% in the denosumab subgroups.
      Lumbar spine BMD increases were significantly greater in the denosumab subgroup
      than the BP subgroups. There were no significant differences in FN BMD increases
      among the three subgroups. Lumbar spine BMD increases were significantly greater
      in the denosumab subgroup than the BP subgroups, whereas FN BMD increases were
      not significant. Denosumab treatment was more effective in increasing BMD and
      therefore has the potential benefit of fracture prevention. Further research is
      warranted to determine the optimal treatment after daily TPTD. (c) 2018 The
      Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American
      Society for Bone and Mineral Research.

PMID- 30283911
TI  - Homocysteine-Lowering Treatment and the Risk of Fracture: Secondary Analysis of a
      Randomized Controlled Trial and an Updated Meta-Analysis.
AB  - High plasma homocysteine is a risk factor for osteoporotic fractures. Several
      studies have assessed the possible preventive effect of homocysteine-lowering B
      vitamin treatment on the risk of fracture with inconclusive results. In the
      current study, we include new results from the Aspirin Folate Polyp Prevention
      Study (AFPPS) together with an updated meta-analysis of randomized controlled
      trials (RCTs). Our objective was to determine whether there is an association
      between homocysteine-lowering B-vitamin treatment and the risk of fracture. The
      AFPPS trial was performed between 1994 and 2004 in nine clinical centers in the
      United States, and 1021 participants were randomized to a daily folic acid dose
      of 1 mg (n = 516) or placebo (n = 505). The main outcome was fracture of any
      type. In addition, we analyzed the risk of hip fracture. In the meta-analysis,
      studies were identified following a search strategy in electronic database and by
      hand searching. Risk ratio with 95% confidence interval (CI) was chosen for
      pooled analyses. In the AFPPS, no statistically significant association was found
      between folic acid treatment and fractures of any type (risk ratio [RR] = 0.95;
      95% CI 0.61-1.48) or hip fracture (RR = 0.98; 95% CI 0.25-3.89). In the meta
      analysis, six RCTs were included with a total of 36,527 participants. For
      interventions including folic acid and/or vitamin B12, the pooled RR for
      treatment was 0.97 (95% CI 0.87-1.09) for fractures of any type (n = 1199) and
      1.00 (95% CI 0.81-1.23) for hip fractures (n = 335). In conclusion, no
      association was found between homocysteine-lowering treatment with B vitamins
      (folic acid and vitamin B12) and the risk of fracture. (c) 2018 The Authors. JBMR
      Plus is published by Wiley Periodicals, Inc. on behalf of American Society for
      Bone and Mineral Research.

PMID- 30283912
TI  - Fracture Healing in Two Adult Patients With Hypophosphatasia After Asfotase Alfa
      Therapy.
AB  - Infants and children with hypophosphatasia (HPP) treated with asfotase alfa show
      improvement in bone mineralization and motor function, but it is unclear whether
      the medication can affect fracture healing in adult HPP patients. We present the
      course of fracture healing in two adults with HPP on enzyme replacement. Case 1
      is a 41-year-old female with infantile-onset HPP who was wheelchair-bound due to
      a nonhealing tibial fragility fracture sustained 3 years before and also had
      nonhealing femoral pseudofracture sustained 17 years before starting asfotase
      alfa therapy in December 2015. One month after medication initiation, she
      underwent elective osteotomy of tibia and fibula with intramedullary nail
      fixation. After 3 months of enzyme replacement, she was full weight-bearing and
      radiographs demonstrated callus formation at osteotomy sites, and at 11 months of
      therapy, radiographs showed union of the osteotomies. By 11 months of asfotase
      alfa therapy, there was near resolution of the femoral pseudofracture without
      interval surgery at this site. Case 2 is a 61-year-old male who showed nonunion
      of a fragility fracture of the right femur 8 years prior, intramedullary nail
      fixation 6 years prior, and stress fracture of the left femoral diaphysis
      sustained 1 year before starting asfotase alfa in October 2015. A trial of
      teriparatide was unsuccessful in healing of these fractures. On asfotase alfa,
      radiographs revealed interval healing of the left femur fracture after 12 months
      and complete healing of the right femur fracture and near resolution of the left
      femur fracture after 16 months of medical therapy. These two adult patients with
      HPP showed significant clinical and radiographic improvements in a total of four
      recalcitrant fractures on enzyme replacement therapy with asfotase alfa. (c) 2018
      The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American
      Society for Bone and Mineral Research.

PMID- 30283913
TI  - Reported Consumption of Low-Calorie Sweetener in Foods, Beverages, and Food and
      Beverage Additions by US Adults: NHANES 2007-2012.
AB  - Background: Low-calorie sweeteners (LCSs), artificial sweeteners, or high
      intensity sweeteners are incorporated into foods, beverages, and food and
      beverage additions (FBAs). Many prior studies have focused on LCS beverage
      consumption, but not included LCS consumption from foods or FBAs. Objectives: We
      aimed to describe the prevalence of LCS consumption by US adults, and to examine
      the relation between intake of products containing LCSs and macronutrients.
      Methods: Two nonconsecutive 24-h dietary recalls from NHANES 2007-2012 and the
      National Cancer Institute usual intake method were used to estimate prevalence of
      LCS intake from foods, beverages, and FBAs, and macronutrients among US adults
      aged >=19 y (n = 14,098, weighted n = 218,391,752) in a cross-sectional study.
      The prevalence of LCS consumption from reported foods, beverages, and FBAs among
      US adults was examined by sociodemographic characteristics and body mass index
      (BMI). Logistic regression estimated ORs and 95% CIs for associations between
      sociodemographic characteristics and LCS use (overall and in foods, beverages,
      and FBAs). Results: Among adults, 47.8% reported intake of >=1 food, beverage, or
      FBA containing LCSs over 2 d. Intake was higher among: women non-Hispanic whites,
      college graduates or higher, and those with higher income and obese BMIs (P <
      0.001). Intake of beverages containing LCSs was higher for ages 51-70 y than 19
      30 y and those with overweight and obese BMIs (P < 0.001) than for normal-weight
      individuals. Calories, carbohydrate, and sugar intake were lower and fiber was
      higher in LCS-consumers than in nonconsumers. Specifically, calories from
      beverages were lower in those who reported LCS intake. Conclusions: Individuals
      reporting LCS consumption demonstrated lower total energy intake than did
      individuals without LCS intake. Although the main source of LCSs in the US adult
      diet was beverages (31.9%), we found that FBAs also present a significant
      contribution (25.2%), surpassing food (9.3%). This enables targeted understanding
      of national consumption of these products as well as dietary education and
      intervention opportunities.

PMID- 30283914
TI  - An Academia-Industry Partnership for Planning and Executing a Community-Based
      Feeding Study.
AB  - A research team from Boston Children's Hospital and Harvard Medical School
      conducted a community-based feeding study in collaboration with Framingham State
      University (FSU) and Sodexo, the food service contractor at FSU. The study was a
      randomized controlled trial, implemented on the FSU campus. For the final year of
      the study, a satellite feeding site was established at Assabet Valley Regional
      Technical High School. The purpose of the study was to assess the biological
      effects of different macronutrient diets. An academia-industry partnership was
      developed to overcome common challenges associated with hospital-based feeding
      studies. Benefits included the following: a study site outside of Boston
      (reducing inconvenience for participants), access to a large commercial kitchen
      and study-specific kiosk (promoting efficiency), collaboration with Sodexo chefs
      (ensuring palatability of meals), and opportunity to procure food from contracted
      vendors. The research (academia) and food service (industry) teams worked
      together to design, plan, and execute intervention protocols using an integrated
      approach. During execution, the research team was primarily responsible for
      overseeing treatment fidelity, whereas the food service team provided culinary
      expertise, with a strong focus on hospitality and food quality. The study was
      conducted in 3 cohorts between August 2014 and May 2017. Participants received
      all of their food for ~30 wk, totaling >160,000 meals. For all 3 cohorts
      combined, 234 participants provided informed consent, 229 started a standard run
      in weight-loss diet, 164 lost a mean +/- SD 12% +/- 2% of baseline body weight
      and were randomly assigned to different macronutrient diets for weight-loss
      maintenance, and 148 completed the study. During the final and largest cohort, as
      many as 114 participants received daily meals concurrently. The daily cost per
      participant for preparation and service of weighed meals and snacks was ~$65.
      This academia-industry partnership provides a model for controlled feeding
      protocols in nutrition research, potentially with enhanced cost-effectiveness,
      practicality, and generalizability. This trial was registered at
      http://www.clinicaltrials.gov as NCT02068885.

PMID- 30283916
TI  - Dietary Consumption of Lutein and Zeaxanthin in Panama: A Cross-Sectional Study.
AB  - Background: The macular pigments of the eye increase with a diet rich in lutein
      and zeaxanthin, both of which are phytochemicals and important for visual health.
      Objective: We aimed to determine the dietary consumption of lutein and zeaxanthin
      in adults working at the Universidad de Panama (University of Panama), Panama
      City. Method: This was a cross-sectional study with 164 subjects including both
      men and women >18 y of age and employed at the University of Panama, Panama City,
      Panama. The data collection was carried out between May and September 2017. A
      semiquantitative food frequency questionnaire was applied with 43 foods high in
      lutein and zeaxanthin, which included eggs as the only source of animal protein,
      23 vegetables, 15 fruits, and 4 foods prepared with corn as an ingredient.
      Results: The mean +/- SD age was 45.7 +/- 12.7 y (72% women). The mean +/- SD and
      median (IQR) lutein consumption were 2.063 +/- 2.334 mg/d and 1.512 (1.385) mg/d,
      respectively; and for zeaxanthin these were 0.858 +/- 0.866 mg/d and 0.550
      (0.819) mg/d, respectively. The food products that contributed the most dietary
      lutein and zeaxanthin were tomatoes, corn tortilla, and egg yolk. Conclusion: The
      consumption of lutein and zeaxanthin is low among people working at the
      University of Panama, and this is not associated with sociodemographic variables.

PMID- 30283915
TI  - A Structural Equation Modelling Approach to Understanding Influences of Maternal
      and Family Characteristics on Feeding Practices in Young Children.
AB  - Background: The family environment is influential for a child's healthy
      development through parent and sibling influences on feeding practices. Multiple
      child households may protect against unhealthy feeding practices, but additional
      children contribute to higher maternal stress. Households of married parents may
      decrease maternal stress by sharing parental demands. Objective: We aimed to
      evaluate the collective influence of maternal stress, marital status, and number
      of children on feeding practices. Methods: Mothers of 2- to 5-y-old children (n =
      278) were recruited mainly on a university campus and completed an online survey
      to examine associations between maternal stress (Depression, Anxiety, Stress
      Scale), number of children, marital status, and feeding practices (restriction
      and pressure to eat; Child Feeding Questionnaire). Relationships were examined
      through the use of multivariate regression and structural equation modelling.
      Results: A mainly married (85%) and Caucasian (73%) sample participated, with
      most mothers reporting multiple children [2 children (45%) or >=3 children
      (24%)]. Marital status was not associated with either feeding practice, i.e.,
      restriction and pressure to eat (P < 0.05). In adjusted models, maternal stress
      (beta = 0.04, SE = 0.01, P = 0.003) and number of children (beta = 0.24, SE =
      0.08, P = 0.003) in the household individually contributed to higher feeding
      restriction; their interaction resulted in lower feeding restriction (beta = 
      0.01, SE = 0.05, P = 0.005). In stratified models, maternal stress was associated
      with restriction in single-child households (beta = -0.03, SE = 0.009, P =
      0.002), but not multiple-child households (beta = -0.004, SE = 0.005, P = 0.40).
      Conclusions: Number of children had no effect on feeding practices individually,
      but may contribute to a less restrictive feeding environment. Additional
      investigation into creating less stressful and more positive feeding environments
      for all mothers can lead to healthier mothers and families.

PMID- 30283917
TI  - Effective mental health interventions to reduce hospital readmission rates: a
      systematic review.
AB  - Background: Hospitals in the United States are financially penalized for having a
      higher than expected thirty-day readmission ratio among patients initially
      hospitalized for heart failure, acute myocardial infarction (AMI), pneumonia,
      chronic obstructive pulmonary disease (COPD), coronary artery bypass graft (CABG)
      surgery, or hip and knee replacement. Patients hospitalized for these conditions
      that have comorbid mental health diagnoses or symptoms are at high risk for
      readmission. Methods: We conducted a systematic review to determine if
      interventions, that are specifically designed to assess or treat mental health
      symptoms, can effectively reduce risk of readmission following hospitalization
      for physical health conditions. We searched on PubMed and Google Scholar for peer
      reviewed articles published between January 2010 and June 2018 that examined the
      impact of mental-health interventions on readmissions for physical conditions.
      Results: After screening 81 full text articles, we found eleven intervention
      studies, one meta-analysis, and one cross-sectional study that met our inclusion
      criteria. Only three of the intervention studies found significant differences in
      readmission rates between intervention and comparison groups. Each of these
      interventions targeted patients after discharge from the hospital. One of the
      interventions was a physical health telemonitoring and individual psychotherapy
      intervention for patients that were initially admitted for heart failure. The
      second intervention was individual and group psychotherapy sessions for patients
      who were initially admitted for AMI. The third intervention was a nurse-driven
      depression care management protocol for home care patients with depressive
      symptoms who were initially admitted for any physical health condition. The cross
      sectional study showed that communities with a stronger, social-based public
      mental health infrastructure had significantly lower physical health readmission
      rates. Conclusions: The literature identified in this review, appears to provide
      support for the use of mental health interventions after discharge as a mechanism
      for reducing physical health condition readmissions. Future research is needed to
      determine if these interventions can specifically reduce thirty-day readmissions
      for the six conditions linked to financial penalties.

PMID- 30283919
TI  - Probing charge transfer characteristics in a donor-acceptor metal-organic
      framework by Raman spectroelectrochemistry and pressure-dependence studies.
AB  - The stimuli responsive behaviour of charge transfer donor-acceptor metal-organic
      frameworks (MOFs) remains an understudied phenomenon which may have applications
      in tuneable electronic materials. We now report the modification of donor
      acceptor charge transfer characteristics in a semiconducting tetrathiafulvalene
      naphthalene diimide-based MOF under applied electrochemical bias and pressure. We
      employ a facile solid state in situ Raman spectroelectrochemical technique,
      applied for the first time in the characterisation of electroactive MOFs, to
      monitor the formation of a new complex TTFTC+-DPNI from a largely neutral system,
      upon electrochemical oxidation of the framework. In situ pressure-dependent Raman
      spectroscopy and powder X-ray diffraction experiments performed in a diamond
      anvil cell revealed blue shifts in the donor and acceptor vibrational modes in
      addition to contractions in the unit cell which are indicative of bond
      shortening. This study demonstrates the utility of in situ Raman spectroscopic
      techniques in the characterisation of redox-active MOFs and the elucidation of
      their electronic behaviours.

PMID- 30283920
TI  - Aggregation of P3HT as a preferred pathway for its chemical doping with F4-TCNQ.
AB  - The chemical doping reaction of P3HT with F4-TCNQ was studied by optical
      absorption spectroscopy, atomic force microscopy, and Kelvin probe force
      microscopy. We demonstrate that P3HT aggregation preferentially occurs before the
      actual charge transfer step takes place, emphasizing the impact of morphology on
      the chemical doping reaction of conjugated polymers at the molecular level.

PMID- 30283918
TI  - Utilising dog-computer interactions to provide mental stimulation in dogs
      especially during ageing.
AB  - Aged dogs suffer from reduced mobility and activity levels, which can affect
      their daily lives. It is quite typical for owners of older dogs to reduce all
      activities such as walking, playing and training, since their dog may appear to
      no longer need them. Previous studies have shown that ageing can be slowed by
      mental and physical stimulation, and thus stopping these activities might
      actually lead to faster ageing in dogs, which can result in a reduction in the
      quality of life of the animal, and may even decrease the strength of the dog
      owner bond. In this paper, we describe in detail a touchscreen apparatus,
      software and training method that we have used to facilitate dog computer
      interaction (DCI). We propose that DCI has the potential to improve the welfare
      of older dogs in particular through cognitive enrichment. We provide hypotheses
      for future studies to examine the possible effects of touchscreen use on
      physiological, behavioural and cognitive measures of dogs' positive affect and
      well-being, and any impact on the dog-owner bond. In the future, collaborations
      between researchers in animal-computer interaction, dog trainers, and cognitive
      scientists are essential to develop the hardware and software necessary to
      realise the full potential of this training and enrichment tool.

PMID- 30283921
TI  - Nonmonotonic thickness-dependence of in-plane thermal conductivity of few-layered
      MoS2: 2.4 to 37.8 nm.
AB  - Recent first-principles modeling reported a decrease of in-plane thermal
      conductivity (k) with increased thickness for few layered MoS2, which results
      from the change in phonon dispersion and missing symmetry in the anharmonic
      atomic force constant. For other 2D materials, it has been well documented that a
      higher thickness could cause a higher in-plane k due to a lower density of
      surface disorder. However, the effect of thickness on the k of MoS2 has not been
      systematically uncovered by experiments. In addition, from either experimental or
      theoretical approaches, the in-plane k value of tens-of-nm-thick MoS2 is still
      missing, which makes the physics on the thickness-dependent k remain ambiguous.
      In this work, we measure the k of few-layered (FL) MoS2 with thickness spanning a
      large range: 2.4 nm to 37.8 nm. A novel five energy transport state-resolved
      Raman (ET-Raman) method is developed for the measurement. For the first time, the
      critical effects of hot carrier diffusion, electron-hole recombination, and
      energy coupling with phonons are taken into consideration when determining the k
      of FL MoS2. By eliminating the use of laser energy absorption data and Raman
      temperature calibration, unprecedented data confidence is achieved. A
      nonmonotonic thickness-dependent k trend is discovered. k decreases from 60.3 W m
      1 K-1 (2.4 nm thick) to 31.0 W m-1 K-1 (9.2 nm thick), and then increases to 76.2
      W m-1 K-1 (37.8 nm thick), which is close to the reported k of bulk MoS2. This
      nonmonotonic behavior is analyzed in detail and attributed to the change of
      phonon dispersion for very thin MoS2 and a reduced surface scattering effect for
      thicker samples.

PMID- 30283922
TI  - Simple construction of ratiometric fluorescent probe for the detection of
      dopamine and tyrosinase by the naked eye.
AB  - In this work, a simple and novel ratiometric fluorescence method based on ROX-DNA
      functionalized CdZnTeS quantum dots (QDs) was developed for the detection of
      dopamine (DA) and tyrosinase (TYR). A ratiometric fluorescent probe was
      constructed by binding phosphorothioate DNA to the metal ions of QDs, which is a
      modification-free and low-cost method. DA was easily oxidized to DA quinone under
      the catalysis of TYR by dissolved O2, which effectively quenched the fluorescence
      of the QDs. Strong linear correlations were achieved for TYR in the range of 10.0
      100.0 ng mL-1 and for DA in the range of 10.0-1000.0 nM. The limit of detection
      was estimated to be as low as 1.05 ng mL-1 for TYR and 1.93 nM for DA. Moreover,
      various colors were displayed in the course of detection, which could be observed
      by the naked eye. Therefore, an on-site and sensitive fluorescence method for the
      visual detection of DA and TYR can be developed. In addition, the findings
      revealed the potential applicability of the ratiometric fluorescent probe for the
      detection of DA and TYR in human serum. This ratiometric fluorescence method is
      not only sensitive and selective but also rapid and convenient for the detection
      of the analytes without sophisticated instrumentation.

PMID- 30283923
TI  - Arylation of benzyl amines with aromatic nitriles.
AB  - In the past years, the activations of aromatic nitriles for radical arylations
      under photoirradiation have been developed. We here report the first example of
      radical arylations using aromatic nitriles without the assistance of
      photoirradiation. Importantly, with this method, the direct arylation of C(sp3)-H
      in benzyl amines provided a practical method for the synthesis of
      diarylmethylamines without the use of precious transition metal catalysts.

PMID- 30283924
TI  - Fabrication and simulation of V-shaped Ag nanorods as high-performance SERS
      substrates.
AB  - Bending straight Ag nanorods (AgNRs) into V-shaped structures can generate a
      higher surface-enhanced Raman scattering (SERS) performance. Numerical
      simulations showed that V-shaped AgNRs with a total length between 300 nm and 800
      nm were more sensitive than equal-length straight AgNRs under a 785 nm laser in
      most cases. It was found that at a laser wavelength between 500 nm and 1000 nm,
      the Raman enhancement factor (EF) of a V-shaped AgNR's 3rd plasmon mode was not
      only optimal among the other major plasmon modes, but also outperformed the
      plasmon modes of straight AgNRs. Besides, a linear relationship between the
      resonance wavelength of the V-shaped AgNR's 3rd mode and its length was observed
      both numerically and experimentally, which was beneficial for the optimization of
      SERS substrates. Under 785 nm laser excitation, V-shaped AgNR substrates with a
      single arm length between 330 nm and 340 nm possessed the highest SERS
      efficiency. This work took AgNR array substrates one step closer to practical
      applications.

PMID- 30283925
TI  - The promising indicators of the thermal and mechanical properties of collagen
      from bass and tilapia: synergistic effects of hydroxyproline and cysteine.
AB  - Collagen has been widely documented as one of the most promising and competitive
      biomaterials for tissue engineering and medical applications. However, the
      properties of collagen differ from one source to another. In the present study,
      type I collagen (COL-I) was extracted and purified from the skins of Japanese sea
      bass (Lateolabrax japonicus) and Nile tilapia (Oreochromis niloticus).
      Ultraviolet (UV) spectroscopy, Fourier transform infrared spectroscopy (FTIR) and
      SDS-PAGE were performed to characterize both COL-Is. The denaturing temperature
      of bass collagen (BC) was observed to be 27.2  degrees C, and 35.3  degrees C for
      tilapia collagen (TC). The content of hydroxyproline was 13.4% in TC, which was
      similar to that in porcine collagen (PC, 13.6%) and higher than that in BC
      (10.3%), while the content of cysteine in TC (0.87%) was significantly higher
      than that in PC (0.04%) and BC (0.35%). After incubation at different
      temperatures for 9 h, more degraded collagen bands appeared in the BC hydrogel
      (BCH) group than in the TC hydrogel (TCH) group, indicating that TCH exhibited
      better thermal stability than BCH. The thermal stabilities of TCH and PC hydrogel
      (PCH) were similar. The compressive stress of TCH was up to 0.099 MPa, while it
      was 0.047 MPa for BCH and 0.003 MPa for PCH. These results demonstrated that the
      content of amino acids (especially hydroxyproline and cysteine) has a synergistic
      effect on the thermal and mechanical properties of BCH, TCH and PCH, which would
      be an indicator of the thermal and mechanical properties of collagen hydrogels in
      future studies.

PMID- 30283926
TI  - Ultrasensitive electrochemical detection of miRNA based on DNA strand
      displacement polymerization and Ca2+-dependent DNAzyme cleavage.
AB  - miRNAs are novel diagnostic and prognostic biomarkers for a diversity of diseases
      like cancers. In this study, an ultrasensitive electrochemical biosensor for
      miRNA evaluation is fabricated. A methylene blue (MB) labeled DNA probe is
      firstly modified on a gold electrode. By employing target induced strand
      displacement amplification and subsequent DNAzyme cleavage cycles, a large number
      of MB molecules are released. The decreased oxidation peak current could be used
      to reveal the miRNA concentration. Based on the two efficient signal
      amplifications, this method shows ultrahigh sensitivity. Its feasibility for the
      analysis of miRNA in cell lysates is also demonstrated. Therefore, the method
      shows attractive potential for promising applications in early diagnosis of
      certain diseases.

PMID- 30283927
TI  - Predicting the structural evolution of Gen- (3 <= n <= 20) clusters: an anion
      photoelectron spectroscopy simulation.
AB  - Spectroscopic evidence for the structural evolution of Gen- (3 <= n <= 20)
      clusters is provided by means of simulated anion photoelectron spectra (PES).
      Both adiabatic detachment energies and HOMO-LUMO gaps of the selected low-lying
      candidates match well with those measured in experiment. This work demonstrates
      that PES is a highly sensitive technique for probing both electronic and
      geometric structures of atomic clusters, whose structural evolution is an
      elemental signature with characteristic features.

PMID- 30283928
TI  - Halogen bond shortens and strengthens the bridge bond of [1.1.1]propellane and
      the open form of [2.2.2]propellane.
AB  - Detailed electronic structural analysis of [1.1.1]propellane and the open form of
      [2.2.2]propellane, especially their highest occupied molecular orbital (HOMO),
      shows the existence of significant electronic congestion at their bridge bond.
      The HOMO of [1.1.1]propellane is a spread-out orbital of its inverted tetrahedral
      bridgehead atoms. The HOMO of the open form of [2.2.2]propellane is an anti
      bonding combination of its bridgehead atoms due to the stabilizing through-bond
      interaction. This unique spatial disposition of the HOMO enables a high electron
      density at the bridgehead atoms. Herein, we utilize the electron scavenging power
      of halogen bond donors to extract a fraction of destabilizing electrons from the
      bridge bond with the aim to alleviate its electronic congestion, which results in
      shortening and strengthening of the bridge bond with a reduction in the bond
      order. This result answers the seminal question raised by K. B. Wiberg in 1983,
      "how can one have a relatively 'strong bond' without much bonding character?"

PMID- 30283930
TI  - Local elasticity in nonlinear rheology of interacting colloidal glasses revealed
      by neutron scattering and rheometry.
AB  - The flow of colloidal suspensions is ubiquitous in nature and industry. Colloidal
      suspensions exhibit a wide range of rheological behavior, which should be closely
      related to the microscopic structure of the systems. With in situ small-angle
      neutron scattering complemented by rheological measurements, we investigated the
      deformation behavior of a charge-stabilized colloidal glass at particle level
      undergoing steady shear. A short-lived, localized elastic response at particle
      level, termed as the transient elasticity zone (TEZ), was identified from the
      neutron spectra. The existence of the TEZ, which could be promoted by the
      electrostatic interparticle potential, is a signature of deformation
      heterogeneity: the body of fluids under shear behaves like an elastic solid
      within the spatial range of the TEZ but like fluid outside the TEZ. The size of
      the TEZ shrinks as the shear rate increases in the shear thinning region, which
      shows that the shear thinning is accompanied by a diminishing deformation
      heterogeneity. More interestingly, the TEZ is found to be the structural unit
      that provides the resistance to the imposed shear, as evidenced by the
      quantitative agreement between the local elastic stress sustained by the TEZ and
      the macroscopic stress from rheological measurements at low and moderate shear
      rates. Our findings provide an understanding on the nonlinear rheology of
      interacting colloidal glasses from a micro-mechanical view.

PMID- 30283931
TI  - Tunable band gap of graphyne-based homo- and hetero-structures by stacking
      sequences, strain and electric field.
AB  - A comprehensive investigation was carried out on graphyne/graphyne (Gyne/Gyne),
      graphyne-like BN/graphyne-like BN (BNyne/BNyne) and graphyne/graphyne-like BN
      (Gyne/BNyne) bilayer structures using van der Waals (vdW)-corrected density
      functional theory. These bilayers exhibited distinct stacking-dependent
      characteristics in their ground state electronic structure and also had different
      responses to external strain and a vertical electric field. For the Gyne/Gyne and
      Gyne/BNyne bilayers, the application of biaxial tensile strain led to an increase
      in the band gap, while the application of biaxial compressive strain in addition
      to uniaxial strain, either under tension or compression, induced a reduction in
      the band gap. However, in the case of the BNyne/BNyne bilayer, the application of
      biaxial tensile strain led to a decrease in the band gap, but an increase in the
      band gap occurred under biaxial compressive strain, which could be explained by a
      change in the ionic nature of the B-N bonds. Under a vertical electric field, the
      band gaps of the homo-bilayers (Gyne/Gyne and BNyne/BNyne) decreased and were
      symmetrical. However, the hetero-bilayer (Gyne/BNyne) exhibited a decreased band
      gap under a positive electric field, but an almost constant band gap under a
      negative electric field. The physical origin of the band gap variation under an
      electric field was unraveled using energy-band theory. Our findings pave the way
      for experimental research and provide valuable insight into two-dimensional vdW
      layered structures for use in next generation flexible nanoelectronics and
      optoelectronic devices.

PMID- 30283932
TI  - Computational strategies to probe CH activation in dioxo-dicopper complexes.
AB  - We employ density functional theory and energy decomposition analysis to probe
      the mechanism of CH activation in dioxo-dicopper complexes. The electrophilicity
      of monodentate N-donor ligands coordinated to Cu is systematically varied to
      examine the response of barriers to the two proposed pathways - one-step oxo
      insertion and two-step radical recombination. Electron-withdrawing ligand
      stabilize the oxo-insertion transition state via charge transfer interactions,
      and therefore lead to lower barriers. On the other hand, barriers to the CH
      activation step in the radical recombination mechanism exhibit almost no
      dependence on N-donor electrophilicity. Based on the similarities between
      calculated and experimental Hammett relationships, the oxo-insertion pathway
      appears to be the preferred mechanism of CH activation in dioxo-dicopper
      catalysts.

PMID- 30283933
TI  - High-resolution vibration-rotational spectra and rotational perturbation of the
      OO-stretching (nu6) band of CH2OO between 879.5 and 932.0 cm-1.
AB  - We report the observation of a rotationally resolved nu6 band associated with the
      OO-stretching mode of the simplest Criegee intermediate, CH2OO, in the range of
      879.5-932.0 cm-1 (11.37-10.73 MUm) at an optical resolution of 0.0015 cm-1. The
      spectra were recorded with a tunable cw external-cavity quantum-cascade laser (EC
      QCL) system coupled with a Herriott multipass absorption cell. Over one thousand
      lines were assigned to determine the rovibrational parameters of the nu6 band.
      Rotational parameters A', B', and C' and higher-order parameters DeltaJ, DeltaJK,
      DeltaK, deltaJ, and deltaK were determined precisely. Rotational perturbations
      for Ka' = 3, Ka' = 6, and Ka' >= 11 on high-J levels were observed. In
      particular, for Ka' = 6, frequency shifts as a function of J' showed an avoided
      crossing; the shifts were analyzed in terms of a Coriolis interaction between
      modes nu6 and nu8 of CH2OO. According to the distinct temporal profiles, lines of
      a hot band near 899.5 cm-1 were also identified.

PMID- 30283929
TI  - Asymmetric synthesis via stereospecific C-N and C-O bond activation of alkyl
      amine and alcohol derivatives.
AB  - This perspective showcases our development of benzylic and allylic amine and
      alcohol derivatives as electrophiles for stereospecific, nickel-catalyzed cross
      coupling reactions, as well as the prior art that inspired our efforts. The
      success of our effort has relied on the use of benzyl ammonium triflates as
      electrophiles for cross-couplings via C-N bond activation and benzylic and
      allylic carboxylates for cross-couplings via C-O bond activation. Our work, along
      with others' exciting discoveries, has demonstrated the potential of
      stereospecific, nickel-catalyzed cross-couplings of alkyl electrophiles in
      asymmetric synthesis, and enables efficient generation of both tertiary and
      quaternary stereocenters.

PMID- 30283934
TI  - Self-assembly of a Si-based cage by the formation of 24 equivalent covalent
      bonds.
AB  - A robust, nano-sized covalent cage, of composition, [(PhSi)6(ctc)4]6- (H6ctc =
      cyclotricatechylene) has been prepared in a simple reaction in good yield. The
      tetrahedral anionic cage is stable in both the solid and solution state and
      exhibits an affinity for Cs+ ions which bind to the internal surface of the cage.

PMID- 30283935
TI  - Neutral and anionic phosphate-diesters as molecular templates for the
      encapsulation of a water dimer.
AB  - The study of water clusters in a confined state has received considerable
      attention. The simplest among such assemblies of water molecules is the water
      dimer. Stabilizing this unit at ambient conditions in an appropriate host
      template, however, has remained a challenge. Herein, we report 2,6
      (diphenylmethyl)-4-iso-propyl-phenyl substituted phosphate diesters (both in
      their neutral and anionic forms) as molecular templates for hosting the water
      dimer. The robustness of the water dimer within the neutral phosphate-diester
      ensemble is remarkable. Even when treated with triethylamine the water dimer is
      not disrupted, while exclusively the P(O)(OH) unit is deprotonated.

PMID- 30283936
TI  - Factors affecting cyclic durability of all-solid-state lithium batteries using
      poly(ethylene oxide)-based polymer electrolytes and recommendations to achieve
      improved performance.
AB  - A detailed experimental analysis of the factors affecting cyclic durability of
      all-solid-state lithium batteries using poly(ethylene oxide)-based polymer
      electrolytes was published in EES by Nakayama et al. We use quantum mechanics to
      interpret these results, identifying processes involved in the degradation of
      rechargeable lithium batteries based on polyethylene oxide (PEO) polymer
      electrolyte with LiTFSI. We consider that ionization of the electrolyte near the
      cathode at the end of the recharge step is probably responsible for this
      degradation. We find that an electron is likely removed from PEO next to a TFSI
      anion, triggering a sequence of steps leading to neutralization of a TFSI anion
      and anchoring of another TFSI to the PEO. This decreases the polymer conductivity
      near the cathode, making it easier to ionize additional PEO and leading to
      complete degradation of the battery. We refer to this as the Cathode
      Overpotential Driven Ionization of the Solvent (CODIS) model. We suggest possible
      ways to confirm experimentally our interpretation and propose modifications to
      suppress or reduce electrolyte degradation.

PMID- 30283937
TI  - Organic crystalline materials in flexible electronics.
AB  - Flexible electronics have attracted considerable attention recently given their
      potential to revolutionize human lives. High-performance organic crystalline
      materials (OCMs) are considered strong candidates for next-generation flexible
      electronics such as displays, image sensors, and artificial skin. They not only
      have great advantages in terms of flexibility, molecular diversity, low-cost,
      solution processability, and inherent compatibility with flexible substrates, but
      also show less grain boundaries with minimal defects, ensuring excellent and
      uniform electronic characteristics. Meanwhile, OCMs also serve as a powerful tool
      to probe the intrinsic electronic and mechanical properties of organics and
      reveal the flexible device physics for further guidance for flexible materials
      and device design. While the past decades have witnessed huge advances in OCM
      based flexible electronics, this review is intended to provide a timely overview
      of this fascinating field. First, the crystal packing, charge transport, and
      assembly protocols of OCMs are introduced. State-of-the-art construction
      strategies for aligned/patterned OCM on/into flexible substrates are then
      discussed in detail. Following this, advanced OCM-based flexible devices and
      their potential applications are highlighted. Finally, future directions and
      opportunities for this field are proposed, in the hope of providing guidance for
      future research.

PMID- 30283938
TI  - A carbon dots/rutin system for colorimetric and fluorimetric dual mode detection
      of Al3+ in aqueous solution.
AB  - In this work, colorimetric and fluorimetric dual mode detection of Al3+ in
      aqueous solution was achieved using a carbon dots/rutin (CDs/rutin) coexisting
      system. Upon addition of Al3+, a yellow Al(iii)-rutin complex was formed without
      any interaction between Al3+ and the carbon dots (CDs). As a result, a new
      absorption peak of the complex at 430 nm increased while the peak of rutin at 360
      nm decreased. Therefore, a ratiometric colorimetric method for the detection of
      Al3+ was built on a good linear relationship between the absorbance ratio (A430
      nm/A360 nm) and the concentration of Al3+ in a wide linear range from 2.0 to 40.0
      MUM, with a limit of detection (LOD) as low as 0.38 MUM. More interestingly, the
      excitation spectrum of the CDs overlapped with the absorption band of the Al(iii)
      rutin complex, resulting in an inner filter effect on the fluorescence of the
      CDs. Accordingly, a fluorimetric approach was developed on an excellent linear
      relationship between (F0 - F)/F0 and the concentration of Al3+ in the range from
      0.8 to 20.0 MUM, with an LOD of 0.32 MUM. Finally, the spiked Al3+ in real
      samples (tap water and lake water) was recovered by the as-proposed dual mode
      detection with high accuracy.

PMID- 30283939
TI  - Vertical vs. adiabatic ionization energies in solution and gas-phase: probing
      ionization-induced reorganization in conformationally-mobile bichromophoric
      actuators using photoelectron spectroscopy, electrochemistry and theory.
AB  - Ionization-induced structural and conformational reorganization in various pi
      stacked dimers and covalently linked bichromophores is relevant to many processes
      in biological systems and functional materials. In this work, we examine the role
      of structural, conformational, and solvent reorganization in a set of
      conformationally mobile bichromophoric donors, using a combination of gas-phase
      photoelectron spectroscopy, solution-phase electrochemistry, and density
      functional theory (DFT) calculations. Photoelectron spectral analysis yields both
      adiabatic and vertical ionization energies (AIE/VIE), which are compared with
      measured (adiabatic) solution-phase oxidation potentials (Eox). Importantly, we
      find a strong correlation of Eox with AIE, but not VIE, reflecting variations in
      the attendant structural/conformational reorganization upon ionization. A careful
      comparison of the experimental data with the DFT calculations allowed us to probe
      the extent of charge stabilization in the gas phase and solution and to parse the
      reorganizational energy into its various components. This study highlights the
      importance of a synergistic approach of experiment and theory to study ionization
      induced structural and conformational reorganization.

PMID- 30283940
TI  - A new class of N-doped ionic PAHs via intramolecular [4+2]-cycloaddition between
      arylpyridines and alkynes.
AB  - Reported herein, for the first time, is a copper-promoted intramolecular [4+2]
      cycloaddition cascade to access ionic N-doped polycyclic aromatic hydrocarbons
      (PAHs) with tunable emission wavelengths. It is shown that the reaction can be
      made catalytic with respect to Cu(OTf)2 when an external oxidant, Selectfluor,
      was used.

PMID- 30283941
TI  - Fragment and cluster ions from gaseous and condensed pyridine produced under
      electron impact.
AB  - We report on direct measurement of all major ion-fragments and cluster-ions
      formed during high-energy electron impact of 2 keV on gaseous and condensed-phase
      pyridine. The ion-fragments of the parent pyridine cation are discussed in groups
      according to the number of atoms from the aromatic ring. The ion yield
      distributions within these groups show significant shifts towards higher masses
      for condensed pyridine compared to gaseous pyridine due to hydrogen migration. A
      wide spectrum of desorbed hydrogenated fragment-ions and ionic clusters with
      masses up to 320 u are observed for pyridine. The ion yields for the protonated
      parent molecule (C5H5NH+), the dehydrogenated dimer (C10H9N2+) and the
      dehydrogenated trimer (C15H12N3+) depend on the mass of the desorbing ionic
      clusters. The strongest cluster signals are assigned to binding between the
      parent cation and subunits of the pyridine molecule. Quantum-chemical
      calculations reveal that the formation of a bond between the pyridine molecules
      and a carbenium ion is crucial for the stability of selected cluster ions.

PMID- 30283942
TI  - High efficiency MAPbI3-xClx perovskite solar cell via interfacial passivation.
AB  - The trap states at the interface between perovskite and charge-transport layer
      have a great influence on the performance of perovskite solar cells. Here, a high
      efficiency MAPbI3-xClx perovskite solar cell has been demonstrated, by
      introducing a thin layer of LiF or PbF2 between the SnO2/perovskite. Improved
      charge collection and reduced interfacial charge recombination are realized,
      leading to remarkable rises of both open-circuit voltage (Voc) and short-circuit
      current (Jsc). This successful interfacial passivation paved a new way to
      fabricate high performance perovskite solar cells with large Voc.

PMID- 30283943
TI  - Laser trapping/confocal Raman spectroscopic characterization of PLGA-PEG
      nanoparticles.
AB  - We have immobilized poly(ethylene glycol) (PEG) on the surfaces of poly(lactic-co
      glycolic acid) (PLGA) nanoparticles by two different chemical methods, i.e.,
      SOCl2 halogenate-alcoholysis and DCC dehydration. The immobilized PLGA
      nanoparticles were characterized by DLS, 1H NMR, FT-IR and laser
      trapping/confocal Raman spectroscopic techniques. As a result, especially the
      Raman spectra which were measured after optically trapping ca. 10 individual
      nanoparticles in solution indicated that the PLGA nanoparticles were successfully
      immobilized with the PEG by the chemical methods.

PMID- 30283944
TI  - Implementation of slow magnetic relaxation in a SIM-MOF through a structural
      rearrangement.
AB  - Here we report the structural flexibility of a Dy-based single-ion magnet MOF in
      which its magnetic properties can be modified through a ligand substitution
      process involving an increase of the charge density of the coordination
      environment.

PMID- 30283945
TI  - Correction: Development of oligonucleotide-based antagonists of Ebola virus
      protein 24 inhibiting its interaction with karyopherin alpha 1.
AB  - Correction for 'Development of oligonucleotide-based antagonists of Ebola virus
      protein 24 inhibiting its interaction with karyopherin alpha 1' by Keisuke Tanaka
      et al., Org. Biomol. Chem., 2018, 16, 4456-4463.

PMID- 30283947
TI  - Inhibition by microbial metabolites of Chinese dark tea of age-related
      neurodegenerative disorders in senescence-accelerated mouse prone 8 (SAMP8) mice.
AB  - Dark tea has a significant effect on the prevention and treatment of age-related
      degenerative diseases. At present, further exploration of its functional
      mechanisms is delayed because of the complexity of post-fermentation microbial
      metabolites during the production phase. In this study, new isolated microbial
      metabolites extracted from dark tea were used to explore the neuroprotective
      effects, and they also helped allow further exploration of the mechanism of dark
      tea. Taking senescence-accelerated mouse prone 8 (SAMP8) mice as a biological
      model, we examined the protective effect on brain neurons of post-fermentation
      microbial metabolites which were extracted from dark tea. The 4-month-old mice
      were given treatments of the same concentration (10 mg kg-1 d-1) which were l
      theanine, 3,3'-azanediylbis(4-hydroxybenzoic acid) (CDT-1) and one of the 8-C N
      ethyl-2-pyrrolidinone substituted flavan-3-ols (CDT-2) by gavage for 14 weeks.
      Relative measurements such as RT-PCR, ELISA, western blotting, and section
      staining (HE, Nissl and myelin) were carried out. The results showed that l
      theanine, CDT-1 and CDT-2 could inhibit the decrease in body weight, and down
      regulate the formation of 4-HNE and ubiquitinated protein aggregates and the
      Abeta metabolic pathway. They could also increase endogenous antioxidant
      capacity, relieve cell hypoxia, and reduce the rate of neuronal apoptosis. This
      means that their protective activity regarding SAMP8 neurons was excellent and
      the activity of CDT-2 was the most significant.

PMID- 30283946
TI  - Gd3+-Ion-induced carbon-dots self-assembly aggregates loaded with a
      photosensitizer for enhanced fluorescence/MRI dual imaging and antitumor therapy.
AB  - The development of multifunctional nanoparticles for tumor theranostics has
      become a research hotspot. Despite the advantages of non-invasive precision
      diagnostics and efficient drug-delivery, these nanoparticles bring two
      significant issues: (i) a potential toxic effect and (ii) difficult clearance. To
      solve these issues, carbon dots (C-dots) are key potential candidates owing to
      their unique properties, such as excellent biocompatibility and rapid renal
      clearance. However, their small size leads to a short circulation time in the
      blood, which causes non-sufficient tumor accumulation for antitumor therapy. To
      reach the balance between an efficient accumulation in a tumor and rapid
      clearance from the body, herein we report a new multifunctional nanoprobe:
      photosensitizer (chlorine e6, Ce6)-loaded assembled C-dots (A-C-dots@Ce6). The A
      C-dots@Ce6 were assembled from negatively-charged discrete C-dots using Gd3+ ions
      as a "glue". which also provided another function of in vivo nanoprobe monitoring
      via magnetic resonance (MR) imaging. Moreover, the nanoprobe exhibited an acidic
      pH-dependent disassembly and drug-release property. Benefiting from these
      advantages, the nanoprobe showed a targeted antitumor effect in A549 tumor
      bearing mice under laser irradiation and gradual disassembly in the tumor for
      later body clearance. Therefore, the nanoprobe potentially provides a new
      strategy to solve the above balance issue, and brightens the future for antitumor
      monitoring and treatment.

PMID- 30283948
TI  - Stereoselective ozonolysis of TMS-substituted allylic alcohol derivatives and
      synthesis of 14R,15S- and 14S,15S-diHETE.
AB  - Ozonolysis of TMS-substituted olefins produces alpha-carbonyl TMS peroxides
      without cleavage of the C[double bond, length as m-dash]C bond. Herein,
      stereochemistry in the ozonolysis was studied using silyl derivatives of (E)- and
      (Z)-(1-TMS)alk-1-en-3-ols. The (E)-isomers afforded the anti-3-siloxy-2-(TMS
      oxy)aldehydes as the major stereoisomer (anti/syn = 3-9 : 1) after reductive work
      up with Ph3P. In contrast, Z-olefins selectively gave the syn isomers with
      syn/anti ratios of 4-19 : 1. Facial selection was speculated based on the Cieplak
      effect. This ozonolysis was successfully applied for the synthesis of 14R,15S-
      and 14S,15S-diHETEs (anti and syn isomers, respectively) in enantioenriched
      forms.

PMID- 30283949
TI  - Hydrogen-bonded six-component assembly for capsule formation based on tetra(4
      pyridyl)cavitand and isophthalic acid linker and its application to
      photoresponsive capsule.
AB  - Two molecules of tetra(4-pyridyl)cavitand 1 and four molecules of isophthalic
      acid linker 2a with a triethylene glycol monomethyl ether (TEG) group self
      assembled into a six-component capsule 12.2a4 through eight pyNHO2C hydrogen
      bonds, which encapsulates one molecule of guest G such as bis(4
      acetoxyphenyl)acetylene and hexakis(4-iodophenyl)benzene to form G@(12.2a4).
      Guest-encapsulation ability and selectivity of 12.2a4 were revealed. trans-5-(p
      Substituted-phenylazo)isophthalic acid with two dichotomous branching TEG groups
      trans-2b serves as a photoresponsive linker to form 12.(trans-2b)4, which
      moderately reduced guest-encapsulation ability upon photoisomerization (at the
      photostationary state, 10% guest release upon subunit-trans-2b/subunit-cis-2b =
      18 : 82).

PMID- 30283950
TI  - Tuning the order of colloidal monolayers: assembly of heterogeneously charged
      colloids close to a patterned substrate.
AB  - We study the behavior of negatively charged colloids with two positively charged
      polar caps close to a planar patterned surface. The competition between the
      different anisotropic components of the particle-particle interaction is able by
      itself to give rise to a rich assembly scenario: colloids with charged surface
      patterns already form different crystalline domains when adsorbed to a
      homogeneously charged substrate. Here we consider substrates composed of
      alternating (negative/neutral, positive/neutral and positive/negative) parallel
      stripes and, by means of Monte Carlo simulations, we investigate the ordering of
      the colloids on changing the number of the stripes. We show that the additional
      competition between the two different lengths scales characterizing the system
      (i.e., the particle interaction range and the size of the stripes) gives rise to
      a plethora of distinct particle arrangements, where some well-defined trends can
      be observed. By accurately tuning the substrate charged motif it is possible to,
      e.g., promote specific particle arrangements, disfavor crystalline domains or
      induce the formation of extended, open clusters.

PMID- 30283951
TI  - Selective electrohydrodynamic concentration of waterborne parasites on a chip.
AB  - Concentrating diluted samples is a key step to improve detection capabilities.
      The wise use of scaling laws shows the advantages of working with sub-microliter
      sized samples. Rapid progress in MEMS technologies has driven the design of
      integrated platforms performing many biochemical operations. Here we report a new
      concentrator device based on electro-hydrodynamic forces which can be easily
      integrated into electrowetting-on-dielectric (EWOD) platforms. This approach is
      label-free and applicable to a wide range of micro-objects. The detection and
      analysis of two common waterborne parasites, Cryptosporidium and Giardia, is a
      perfect test case due to their global health relevance. By fully controlling the
      interplay of the various forces acting on the micron-sized Cryptosporidium parvum
      and Cryptosporidium muris oocysts, we show that it is possible to concentrate
      them on the side of a 10 MUL initial drop and then extract them efficiently from
      a droplet of a few hundred nanoliters. We performed a finite element modeling of
      the forces acting on the parasites' oocysts to optimize the electrodes' shapes.
      We obtained state-of-the-art concentration factors of 12 +/- 0.4 times and 2 to 4
      times in the sub-region of the drop and the extracted droplet, respectively, with
      an efficiency of 70 +/- 6%. Furthermore, this device had the ability to
      selectively concentrate parasites of different species out of a mix. We
      demonstrated this by segregating C. parvum oocysts from either Giardia lamblia
      cysts or its related species, C. muris oocysts.

PMID- 30283952
TI  - Diverse reactivity of a boraguanidinato germylene toward organic pseudohalides.
AB  - The reactions of the boraquanidinato germylene (i-Pr)2NB(NDmp)2Ge (1) (Dmp = 2,6
      Me2C6H3) with RN3 and RNCS produced rare examples of Ge2N and Ge3S rings, while
      the treatment of 1 with RNCO led to an insertion into the N-Ge bond leading to a
      novel type of germylene stabilized within a six membered ring, i.e.
      [N(R)C(O)N(Dmp)B(N(i-Pr)2)N(Dmp)]Ge (R = t-Bu or Ad).

PMID- 30283953
TI  - Iodine-mediated regio- and stereoselective iodothiocyanation of alkynes in
      aqueous ethanol.
AB  - Iodothiocyanation of alkynes with ammonium thiocyanate (NH4SCN) and molecular
      iodine (I2) has been demonstrated in aqueous ethanol, which enables efficient
      synthesis of a series of functional beta-iodo vinylthiocyanates in good to
      excellent yields under mild reaction conditions without the need for any
      protection.

PMID- 30283954
TI  - Recent progress in the synthesis of phosphorus-containing indole derivatives.
AB  - Phosphorus-containing indole derivatives represent a special class of phosphorus
      containing nitrogen heterocycles, which not only widely exist in pharmaceutical
      agents, but also have widespread applications in materials science and organic
      synthesis as ligands and intermediates. The synthesis of such compounds is of
      current interest, with two major synthetic strategies being established. This
      review summarizes the recent progress in this field, including the advantages and
      limitations of each subdivisional tactic, briefly discusses the reaction
      mechanisms and challenges, and outlines the synthetic opportunities still open.

PMID- 30283955
TI  - Modeling coupled kinetics of antimony adsorption/desorption and oxidation on
      manganese oxides.
AB  - Understanding the kinetic reactions of antimony (Sb) at the MnO2-water interface
      is essential for predicting the dynamic behavior of Sb in soil environments. In
      this study, we developed a quantitative model for assessing the coupling between
      Sb(iii) oxidation and Sb(iii)/Sb(v) adsorption/desorption kinetics and the role
      of each individual reaction process in controlling the overall reaction rates.
      Based on our modeling results, Sb(iii) oxidation rates were very fast at the
      early stages of the reactions and may significantly slow down with time, and
      Sb(iii) and Sb(v) showed different adsorption behavior on delta-MnO2. Our
      kinetics model is able to account for different adsorption/desorption kinetics of
      Sb(iii) and Sb(v) and the changes of Sb(iii) oxidation rates during the coupled
      kinetic processes, which provides a general modeling framework for predicting Sb
      kinetic behavior at the MnO2-water interface.

PMID- 30283956
TI  - Heavier pnictinidene gold(i) complexes.
AB  - N,C,N-Chelated pnictinidenes ArE [where E = As, Sb or Bi; Ar = 2,6-(tBuN[double
      bond, length as m-dash]CH)2C6H3] were used as ligands for the coordination of
      various gold(i) complexes. Thus, the reaction of ArE with [AuCl(Me2S)] gave
      complexes [AuCl(ArE)] [where E = As (1) or Sb (2)] that exhibited only limited
      stability in solution. By contrast, the reaction of ArBi with [AuCl(Me2S)] led to
      the immediate deposition of gold metal and the oxidation of the bismuth atom
      giving ArBiCl2. The treatment of a tetrameric gold alkynyl complex [Au(C[triple
      bond, length as m-dash]CPh)]4 with ArAs and ArSb gave ionic compounds
      [Au(ArAs)2]+[Au2(C[triple bond, length as m-dash]CPh)3]- [denoted as
      3+[Au2(C[triple bond, length as m-dash]CPh)3]-] and [Au(ArSb)2]+[Au(C[triple
      bond, length as m-dash]CPh)2]- [denoted as 4+[Au(C[triple bond, length as m
      dash]CPh)2]-], respectively. Finally, the reaction of ArE with the carbene
      gold(i) complex [Au(IPr)(MeCN)]+[BF4]- [where IPr = 1,3-bis(2,6
      diisopropylphenyl)imidazolin-2-ylidene, MeCN = acetonitrile] produced ionic
      complexes [Au(IPr)(ArE)]+[BF4]- [for cations: E = As (5+), Sb (6+) or Bi (7+)].
      All complexes were characterized using 1H and 13C NMR, high mass accuracy
      electrospray ionization mass spectrometry (ESI-MS), IR and Raman spectroscopy and
      (except for 1) by single-crystal X-ray diffraction analysis. Furthermore, the
      structure and bonding of both neutral and ionic complexes with different
      coordination patterns have also been investigated in detail using a Density
      Functional Theory (DFT) computational approach.

PMID- 30283958
TI  - Regiospecific formal [3 + 2] annulation of tert-propargyl alcohols with acyclic
      1,3-diketones via the cycloisomerization of homoallenyl ketones.
AB  - A one-pot, regiospecific synthesis of dihydrofurans bearing a quaternary centre
      and tetrasubstituted furans is developed from the formal [3 + 2] annulation of
      tert-propargyl alcohols and 1,3-diketones under Ca(ii)/DBU conditions. The
      reaction proceeds through the SN2I mechanism to form homoallenyl ketone and a
      subsequent cycloisomerization to yield novel and new chemical entities of
      privileged scaffolds.

PMID- 30283957
TI  - Flexible and enhanced multicolor-emitting films co-assembled by lanthanide
      complexes and a polymerizable surfactant in aqueous solution.
AB  - Lanthanide complex doped lyotropic liquid crystals (LLCs) are soft materials
      which are impressive due to their excellent luminescence efficiencies and
      stabilities. The introduction of lanthanide complexes into polymerizable LLCs,
      however, may produce organized films with better optical and mechanical
      properties through in situ photopolymerization. An environmentally friendly
      strategy to fabricate flexible multicolor-emitting films has been developed
      through co-assembling red-/green-emitting trisdipicolinate lanthanide complexes
      [choline]3[Ln(DPA)3] (Ln-DPA, Ln = Eu, Tb) into LLC matrices mainly via
      electrostatic interaction and further photopolymerization. The LLCs were
      constructed from a polymerizable surfactant, 3-dodecyl-1-vinylimidazolium bromide
      (C12VIMBr), in aqueous solution. The maintenance of the well-defined LLC
      nanostructures in the luminescent films was validated by small-angle X-ray
      scattering (SAXS) as well as scanning electron microscopy (SEM) measurements.
      Remarkably, the lifetime and absolute luminescence quantum efficiency of such
      films have been improved significantly compared with those of the corresponding
      solid Eu-DPA complex or in aqueous solution and LLC matrices. Through tuning the
      molar ratio of Eu-DPA to Tb-DPA complexes, the emission color of the films could
      be finely-tailored between red and green in the CIE chromaticity diagram.
      Furthermore, the films also possessed certain mechanical strength and stability
      against pH, metal ions, and temperature, indicating their potential application
      as robust luminescent materials.

PMID- 30283959
TI  - Drug and chemical induced photosensitivity from a clinical perspective.
AB  - Drug photosensitivity is a relatively common occurrence and a range of mechanisms
      may be involved. Some of these mechanisms will be discussed, including the most
      common, that of drug phototoxicity. Different types of photosensitivity are
      addressed with respect to clinical presentation, mechanisms and additionally the
      contribution to our understanding through clinically directed investigations and
      regulatory requirements. Repeated controlled therapeutic use of drug
      phototoxicity, with psoralen-UVA (PUVA) photochemotherapy and photodynamic
      therapy (PDT) will also be discussed. Finally, the potential for drug-induced
      photocarcinogenesis will also be covered.

PMID- 30283960
TI  - Electrochemical impedance spectroscopy reveals a new mechanism based on
      competitive binding between Tris and protein on a conductive biomimetic
      polydopamine surface.
AB  - A novel mechanism was developed to study the interaction of mussel inspired
      polydopamine surfaces with bovine serum albumin using cyclic voltammetry and
      electrochemical impedance spectroscopy supplemented with XPS, IR spectroscopy, UV
      spectroscopy and atomic force microscopy. The polydopamine surfaces reveal
      different mechanisms that give a new insight into understanding the interaction
      with BSA under the variable conditions used for PDA preparation and BSA
      adsorption. The study provides an in-depth analysis of the orientations and
      interactions of BSA with polydopamine surfaces. The protein interaction behavior
      changed significantly in different environments including different pH values and
      concentrations of buffer and it revealed a competitive binding mechanism of
      protein binding. The study provides an outlook for studying the interaction of
      protein foulants with PDA, which should be carried out in nucleophilic buffers,
      while the covalent binding or immobilization of biomolecules to PDA surfaces
      should be carried out in non-nucleophilic buffer for higher efficiency.

PMID- 30283961
TI  - Hole transporting materials for perovskite solar cells: a chemical approach.
AB  - Photovoltaic solar cells based on perovskites have come to the forefront in
      science by achieving exceptional power conversion efficiencies (PCEs) in less
      than a decade of research. This "still young" generation of solar cells is
      currently rivalling, in PCEs, well-established technologies, such as cadmium
      telluride (CdTe) and silicon. Further improvements in device stability by means
      of innovative materials are yet to come, with technology becoming closer to
      meeting the market requirements. Emerging from this groundbreaking discovery, a
      great number of charge transporting materials have flourished, which is
      particularly true for hole transporting materials (HTMs). The huge number of
      molecules prepared stem from design and engineering of a wide variety of new and
      also chemically modified old molecules where organic synthesis has played a
      fundamental role. In this review, the contribution of chemistry through those
      synthetic protocols used for producing new and innovative HTMs from relatively
      simple organic molecules is presented in a rational and systematic manner. The
      variety and impact of synthetic strategies followed, the structure-property
      relationship and stability, conductivity and device performance are highlighted
      from a chemical viewpoint.

PMID- 30283962
TI  - Manipulating cell fate: dynamic control of cell behaviors on functional
      platforms.
AB  - The cell microenvironment choreographs the behaviors of cells through multiple
      well-controlled signals. For basic biological study and cell-based therapies, it
      is essential to decipher the complicated cell-matrix interactions, and to develop
      ways to mimic the dynamic microenvironment so that desired biological functions
      of cells can be guided. For this, biomaterials with the ability to
      spatiotemporally impart biochemical and biophysical cues to manipulate cell fate
      have been developed recently. The dynamic property and programmable features of
      stimuli-responsive biointerfaces endow them with the outstanding ability to
      develop advanced biological systems. In this review, we illustrate the recent
      progress of stimuli-responsive biosystems with a particular emphasis on their
      explorations for cell-based fundamental studies, disease diagnosis and
      regenerative therapy. Some basic principles and strategies for the design of
      dynamic platforms are also discussed in this review. Finally, we conclude with an
      outlook on current challenges and future of dynamic platforms for cell study and
      biomedical applications. Overall, we anticipate that this review will boost the
      development of dynamic and multifunctional biosystems by inspiring interest from
      various disciplines, including chemistry, materials science, cell biology,
      nanotechnology, biomedical engineering, as well as clinical research.

PMID- 30283963
TI  - Constructing reduction-sensitive PEGylated NIRF mesoporous silica nanoparticles
      via a one-pot Passerini reaction for photothermal/chemo-therapy.
AB  - In this work, we decorated the surface of MSNs by a one-pot Passerini reaction
      using near-infrared fluorescence BODIPY and poly(ethylene glycol) with an
      aldehyde group (PEG-CHO) for the first time. Doxorubicin (Dox) was loaded to
      demonstrate the reduction response. The formed MSNs neatly integrate
      chemotherapy, photothermal therapy and near-infrared fluorescence (NIRF) imaging.

PMID- 30283964
TI  - Formation of polyhedral vesicle gels from catanionic mixtures of hydrogenated and
      perfluorinated surfactants: effect of fluoro-carbon alkyl chain lengths.
AB  - The effects of alkyl chain length of anionic fluorinated fatty acid surfactants,
      CnF2n+1COOH (n = 7-11), mixed with one cationic hydrocarbon surfactant,
      tetradecyltrimethylammonium hydroxide (TTAOH), on the formation of polyhedral
      vesicle gels were investigated in aqueous solutions. On the basis of phase
      behavior mapping, C8F17COOH, C9F19COOH, C10F21COOH and C11F23COOH except
      C7F15COOH all formed polyhedral vesicle gels when they were mixed with TTAOH
      under certain mixed ratios, which was demonstrated by freeze-fracture
      transmission electron microscopy (FF-TEM) measurements. Meanwhile, the following
      observation was not observed: the longer the fluorinated alkyl chain, the more
      effective the formation of gels by fluorinated fatty acids. The formation of the
      faceted vesicle gels was determined both by the rigidity of the fluorinated alkyl
      chain and the co-crystallization of fluorocarbon chains and hydrocarbon chains,
      as revealed by the results of differential scanning calorimetry (DSC), wide angle
      X-ray scattering (WAXS) and 19F NMR measurements. Furthermore, the polyhedral
      vesicle gels showed high viscoelasticity, which increased clearly with increasing
      fluorinated alkyl chain length, indicating that the viscoelastic property of the
      polyhedral vesicle gel was a result of the crystalline state of the polyhedral
      vesicle bilayers at room temperature. As far as we know, such polyhedral vesicle
      gels formed from perfluorinated and hydrocarbon surfactant mixtures have been
      rarely reported. Our study can be a great advancement in fundamental research of
      surfactant vesicle gels.

PMID- 30283965
TI  - The cyclo-Sb6 ring in the [Sb6(RuCp*)2]2- ion.
AB  - The [Sb6(RuCp*)2]2- (1) anion represents the first example of a Zintl cluster
      with a boat-like cyclo-Sb6 subunit and the first ruthenium polyantimonide
      complex. The anion is dynamic in solution and fragments in the gas phase.
      Structural parameters and DFT calculations suggest the possibility of Sb[double
      bond, length as m-dash]Sb double bond character.

PMID- 30283966
TI  - A hexadecanuclear silver alkynyl cluster based NbO framework with triple
      emissions from the visible to near-infrared II region.
AB  - Compared to emissive silver-thiolate clusters, their alkynyl cousins are,
      however, usually luminescence silent. Herein we report a novel silver-alkynyl
      cluster based NbO-type framework (SD/Ag18) showing unprecedented triple emission
      spanning from the visible to near-infrared (NIR) region. It is a 3D framework
      constructed from a [Cl@Ag16] cluster based unit, which is further quadruply
      bridged by the surrounding four Ag atoms through AgAg interactions, giving a 4
      connected NbO topology. Although SD/Ag18 exhibits weak orange-red emission at
      room temperature, its emission becomes strong upon cooling, with three emission
      maxima at 524, 647 and 1036 nm, respectively, covering both the visible and NIR
      regions. The visible emissions involve triplet alkynyl-to-metal charge transfer
      mixed with a cluster-centered state, whereas the participation of cPrC[triple
      bond, length as m-dash]C- in the frontier orbitals of the cluster may be
      responsible for the NIR emission. The unusual emissions, especially in the NIR-II
      region, are observed, for the first time, in silver complexes.

PMID- 30283967
TI  - First enantioselective total synthesis of altersolanol A.
AB  - The first enantioselective total synthesis of altersolanol A, a secondary
      metabolite from the endophytic fungi Stemphylium globuliferum and Alternaria
      solani, is described. The key step towards the tetrahydroanthraquinone core was
      an asymmetric Diels-Alder (D-A) cycloaddition promoted by (R)-3,3'-diphenyl
      BINOL/boron Lewis acid with good to excellent yields and excellent diastereo- and
      enantioselectivity (>95 : 5 dr and 98 : 2 er).

PMID- 30283968
TI  - Metal-free synthesis of fulleropyrrolidin-2-ols: a novel reaction of
      [60]fullerene with amines and 2,2-disubstituted acetaldehydes.
AB  - A series of scarce fulleropyrrolidin-2-ols were synthesized by the facile one
      step reaction of [60] fullerene with inexpensive and readily accessible amines
      and 2,2-disubstituted acetaldehydes without the addition of valuable metal salts
      in moderate yields, comparable to those for most monoadducts reported previously.
      This strategy exhibits a broad substrate scope and excellent functional group
      tolerance. A plausible reaction pathway for the formation of fulleropyrrolidin-2
      ols is proposed to elucidate the above reaction process.

PMID- 30283969
TI  - Investigation on the growth mechanism of SiC whiskers during microwave synthesis.
AB  - Silicon carbide (SiC) whiskers with different morphologies are fabricated by
      microwave heating of SiO2-coated coal mineral particles at different temperatures
      and different holding times in an oxygen-containing environment. The atomic
      diffusion processes and growth mechanism of the SiC whiskers are simulated. It is
      found that a closed capsule of SiO2 appears during microwave heating, within
      which the SiC whiskers are formed. SiC crystals can be prepared at 1100  degrees
      C for 10 min. The optimized synthesis condition is approximately 1100  degrees C
      for 20 min. Higher temperatures or/and holding times lead to the re-oxidation of
      the SiC crystals. A layer of amorphous SiO2 wraps around the SiC whisker surface
      and generates coated composites at all temperatures. Crystallite knots are
      observed embedding on the SiC whiskers at 1300  degrees C due to the surface
      cleaning and activating effects of microwave plasma. The knots are smoothed at
      1500  degrees C due to local atomic diffusion and grain growth motivated by the
      microwave coupling effect. The variations in the microwave plasma and the
      coupling effect at different heating stages also give rise to unique growth
      phenomena. For the sample synthesized at 1100  degrees C for 20 min, the high
      permittivity values present in the SiC whiskers lead to the excellent EM
      absorption properties at high frequency.

PMID- 30283970
TI  - One-pot synthesis of polyfunctionalized quinolines via a copper-catalyzed tandem
      cyclization.
AB  - An efficient one-pot approach for the synthesis of polyfunctionalized quinolines
      was developed via a sequence of copper-catalyzed coupling reaction/propargyl
      allenyl isomerization/aza-electrocyclization. Easily available starting
      materials, mild conditions, and a wide substrate scope make this approach
      potentially useful.

PMID- 30283971
TI  - First principles studies of the interactions between alkali metal elements and
      oxygen-passivated nanopores in graphene.
AB  - We characterize the structure-property relationship of alkali metal elements in
      oxygen-passivated graphene pores using the density functional theory that
      accounts for quantum mechanical effects and charge transfer. Our description is
      based on the structural and electronic properties of the system and shows common
      trends among the different alkali metals and pores. We find that these nanopores
      which serve as docking sites for alkali metal elements give the strongest binding
      when the size of the pore is similar to the element's van der Waals radius. A
      linear correlation between the binding energy and the energy location of the
      alkali element valence state is found for all elements and pores. Analysis of the
      charge transfer reveals that alkali adsorption increases the local charge in the
      perimeters of the pore by amounts that depend on the geometry. Moreover, charge
      distributions in pristine graphene resemble those of an ideal conductor despite
      its semimetallic character and atomic thickness while oscillations in the
      vicinity of O-passivated nanopores are observed. Our results suggest that charge
      transfer is localized within a few nanometers of the pore and, therefore, allude
      to high density energy storage. The outcomes of this work are significant towards
      the application of porous graphene as effective membranes for ion filtration of
      water and electrode applications.

PMID- 30283972
TI  - Hydration of 3-hydroxy-4,4-dimethylglutaric acid with dimethylamine complex and
      its atmospheric implications.
AB  - Atmospheric aerosols have a tremendous influence on visibility, climate, and
      human health. New particle formation (NPF) is a crucial source of atmospheric
      aerosols. At present, certain field observations and experiments have discovered
      the presence of 3-hydroxy-4,4-dimethylglutaric acid (HDMGA), which may
      participate in NPF events. However, the nucleation mechanism of HDMGA has not
      been clearly understood. In addition, dimethylamine (DMA) is an important
      precursor of nucleation. The nucleation mechanism involving HDMGA and DMA has not
      been studied. In this study, the most stable structures of (HDMGA)(H2O)n (n = 0
      3) and (HDMGA)(DMA)(H2O)n (n = 0-3) were obtained by using M06-2X coupled with
      the 6-311++G(3df,3pd) basis set. The alpha-carboxyl group is directly attached to
      the amino group in all the most stable configurations. Proton transfer enhances
      the strength of a hydrogen bond, as well as promotes the generation of a global
      minimum structure. Temperature has a considerable influence on the distribution
      of isomers for (HDMGA)(DMA)(H2O)3 as compared to the other investigated clusters.
      The Gibbs free energy values reveal that most of the clusters can exist in NPF,
      except for (HDMGA)(H2O)1. The process of adding a cluster of (H2O)n more likely
      occurs in the atmosphere than gradually adding a single water molecule.

PMID- 30283973
TI  - Hard convex lens-shaped particles: metastable, glassy and jammed states.
AB  - We generate and study dense positionally and/or orientationally disordered,
      including jammed, monodisperse packings of hard convex lens-shaped particles
      (lenses). Relatively dense isotropic fluid configurations of lenses of various
      aspect ratios are slowly compressed via a Monte Carlo method based procedure.
      Under this compression protocol, while 'flat' lenses form a nematic fluid phase
      (where particles are positionally disordered but orientationally ordered) and
      'globular' lenses form a plastic solid phase (where particles are positionally
      ordered but orientationally disordered), 'intermediate', neither 'flat' nor
      'globular', lenses do not form either mesophase. In general, a crystal solid
      phase (where particles are both positionally and orientationally ordered) does
      not spontaneously form during lengthy numerical simulation runs. In
      correspondence to those volume fractions at which a transition to the crystal
      solid phase would occur in equilibrium, a 'downturn' is observed in the inverse
      compressibility factor versus volume fraction curve beyond which this curve
      behaves essentially linearly. This allows us to estimate the volume fraction at
      jamming of the dense non-crystalline packings so generated. These packings are
      nematic for 'flat' lenses and plastic for 'globular' lenses, while they are
      robustly isotropic for 'intermediate' lenses, as confirmed by the calculation of
      the tau order metric, among other quantities. The structure factors S(k) of the
      corresponding jammed states tend to zero as the wavenumber k goes to zero,
      indicating they are effectively hyperuniform (i.e., their infinite-wavelength
      density fluctuations are anomalously suppressed). Among all possible lens shapes,
      'intermediate' lenses with aspect ratio around 2/3 are special because they are
      those that reach the highest volume fractions at jamming while being positionally
      and orientationally disordered and these volume fractions are as high as those
      reached by nematic jammed states of 'flat' lenses and plastic jammed states of
      'globular' lenses. All of their attributes, taken together, make such
      'intermediate' lens packings particularly good glass-forming materials.

PMID- 30283974
TI  - Preparation and characterization of pyrene modified uridine derivatives as
      potential electron donors in RNA.
AB  - Charge transfer across double stranded DNA was observed for the first time about
      20 years ago, and ever since it has been the subject of a large number of
      studies. RNA has been hardly investigated in this regard, which not least is due
      to the lack of suitably functionalized ribonucleotide building blocks to serve as
      electron sources upon incorporation into oligoribonucleotides. We have
      synthesized two uridine derivatives carrying pyrene or dimethylaminopyrene linked
      to C5 of the nucleobase. The key to successful synthesis was the adaptation of
      Suzuki-Miyaura conditions to the coupling of the pyrene moiety with the
      ribonucleoside. Final decoration of the pyrenylated nucleosides with standard 5'
      O- and 2'-O-protecting groups and subsequent 3'-O-phosphitylation delivered the
      building blocks for incorporation into RNA. Spectroscopic analysis of the two
      pyrenylated uridines and of the accordingly modified oligonucleotides showed that
      in particular the dimethyaminopyrene functionalized nucleoside is a promising
      candidate as an electron source for RNA charge transport studies.

PMID- 30283975
TI  - Surgical trends and patient factors associated with the treatment of apical
      pelvic organ prolapse from a national sample.
AB  - INTRODUCTION AND HYPOTHESIS: Prolapse of the vaginal apex can be treated using
      multiple surgical modalities. We describe national trends and patient
      characteristics associated with the surgical approach and compare perioperative
      outcomes of abdominal versus vaginal repair of apical pelvic organ prolapse
      (POP). METHODS: The 2006-2012 National Surgical Quality Improvement Program
      Database was queried for abdominal sacrocolpopexy (ASC) and vaginal apical
      suspensions. Patients were stratified by whether or not concomitant hysterectomy
      (CH) was performed or whether or not they were post-hysterectomy (PH).
      Multivariate logistic regressions were adjusted for confounding variables.
      RESULTS: A total of 6,147 patients underwent apical POP repair: 33.9% (2,085)
      ASCs, 66.1% (4,062) vaginal suspensions. 60.0% (3,689) underwent CH. In all
      cohorts, older patients were less likely to have ASC (CH: OR 0.48, CI 0.28-0.83,
      p = 0.008 for age >= 60; PH: OR 0.28, CI 0.18-0.43, p < 0.001). Over time, the
      proportion of all vaginal and abdominal repairs remained relatively stable. Use
      of minimally invasive ASC, however, increased over the study period (trend p <
      0.001), and use of mesh for vaginal suspensions decreased (p < 0.001). ASC had a
      longer median operative time (PH 174 vs 95 min, p < 0.001; CH 192 vs 127 min, p <
      0.001). Complication rates were the same for vaginal repairs and ASC, overall and
      when sub-stratified by hysterectomy status. CONCLUSIONS: Nationally, most apical
      POP repairs are performed via a vaginal route. Older age was predictive of the
      vaginal route for both CH and PH groups. ASCs had longer operative times. There
      has been increased utilization of minimally invasive ASC and decreased use of
      mesh-augmented vaginal suspensions over time.

PMID- 30283976
TI  - Potential application of cell reprogramming techniques for cancer research.
AB  - The ability to control the transition from an undifferentiated stem cell to a
      specific cell fate is one of the key techniques that are required for the
      application of interventional technologies to regenerative medicine and the
      treatment of tumors and metastases and of neurodegenerative diseases.
      Reprogramming technologies, which include somatic cell nuclear transfer, induced
      pluripotent stem cells, and the direct reprogramming of specific cell lineages,
      have the potential to alter cell plasticity in translational medicine for cancer
      treatment. The characterization of cancer stem cells (CSCs), the identification
      of oncogene and tumor suppressor genes for CSCs, and the epigenetic study of CSCs
      and their microenvironments are important topics. This review summarizes the
      application of cell reprogramming technologies to cancer modeling and treatment
      and discusses possible obstacles, such as genetic and epigenetic alterations in
      cancer cells, as well as the strategies that can be used to overcome these
      obstacles to cancer research.

PMID- 30283977
TI  - Dynamics and mechanisms of posterior axis elongation in the vertebrate embryo.
AB  - During development, the vertebrate embryo undergoes significant morphological
      changes which lead to its future body form and functioning organs. One of these
      noticeable changes is the extension of the body shape along the antero-posterior
      (A-P) axis. This A-P extension, while taking place in multiple embryonic tissues
      of the vertebrate body, involves the same basic cellular behaviors: cell
      proliferation, cell migration (of new progenitors from a posterior stem zone),
      and cell rearrangements. However, the nature and the relative contribution of
      these different cellular behaviors to A-P extension appear to vary depending upon
      the tissue in which they take place and on the stage of embryonic development. By
      focusing on what is known in the neural and mesodermal tissues of the bird
      embryo, I review the influences of cellular behaviors in posterior tissue
      extension. In this context, I discuss how changes in distinct cell behaviors can
      be coordinated at the tissue level (and between tissues) to synergize, build, and
      elongate the posterior part of the embryonic body. This multi-tissue framework
      does not only concern axis elongation, as it could also be generalized to
      morphogenesis of any developing organs.

PMID- 30283978
TI  - Thermodynamic Characterization of Mixed Monolayers of a Novel Oxazolidine
      Derivative and Phospholipids.
AB  - Oxazolidine derivatives (OxD) are five ring-membered compounds that contain at
      least one oxygen and nitrogen in their molecular structure. OxD are known due to
      several therapeutic activities such as anticancer and antibiotic properties. In
      this paper, we performed a thermodynamic analysis of the mixed films composed by
      dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphoethanolamine (DPPE),
      dipalmitoyl phosphatidylcholine (DPPC) or L-alpha phosphatidylcholine (PC) with a
      novel oxazolidine derivate (OxD). Relevant thermodynamic parameters such as
      excess areas (DeltaAE), excess free energies (DeltaG), and Gibbs free energy of
      mixing (AGmix) were derived from the surface pressure data. The topographical
      analysis was performed using atomic force microscopy. Based on the calculated
      values of the thermodynamic parameters, we observed that the miscibility of the
      mixed films was directly dependent on their composition. DPPG/OxD and DPPE/OxD
      systems present the best-mixed character at low pressures at OxD molar fraction
      equivalent to 0.25.

PMID- 30283980
TI  - No significant impact of patient age and prior treatment profile with docetaxel
      on the efficacy of cabazitaxel in patient with castration-resistant prostate
      cancer.
AB  - BACKGROUND: The correlation of the oncological outcomes of docetaxel and
      cabazitaxel in Japanese metastatic castration-resistant prostate cancer (mCRPC)
      patients has not been unclear. MATERIALS AND METHODS: This study included a total
      of 47 consecutive Japanese mCRPC patients treated with cabazitaxel and assessed
      the prognostic significance of cabazitaxel, focusing on patient age and the
      correlation of efficacy between docetaxel and cabazitaxel. RESULTS: Prostate
      specific antigen (PSA) decline was observed in 27 patients (57.4%), including 19
      (40.0%) achieving the response defined by PSA decline >= 30%. The median overall
      survival (OS) periods after the introduction of cabazitaxel was 16.1 months.
      Twenty (42.6%) were judged to have responded to cabazitaxel with a PSA decrease
      >= 30% from the baseline. A 30% PSA response to cabazitaxel was achieved in 4
      (50.0%) patients with ? 75 years (n = 8) and 16 (41.0%) patients with less than
      75 years (n = 39). There was no significant correlation between the PSA response
      and patients' age (p = 0.707). A 30% PSA response to cabazitaxel was achieved in
      13 (46.4%) and 7 (36.8%) patients with and without that to docetaxel,
      respectively. A 30% PSA response to cabazitaxel was achieved in 5 (16.6%) and 7
      (41.2%) patients who had treated with less than 10 cycles docetaxel or 10 ?
      cycles, respectively. Univariate and multivariate analyses revealed that there
      were no significant correlation of patient age (p = 0.537), the response to prior
      docetaxel therapy (p = 0.339) or cycles of docetaxel therapy (p = 0.379) with
      shorter OS. CONCLUSION: These results indicate that the introduction of
      cabazitaxel for Japanese mCRPC patients could result in oncological outcomes
      without any association with patient's age and the profiles of previous docetaxel
      therapy.

PMID- 30283979
TI  - An Analysis of IS630/Tc1/mariner Transposons in the Genome of a Pacific Oyster,
      Crassostrea gigas.
AB  - Transposable elements represent the DNA fragments capable of increasing their
      copy number and moving within the genome. Class II mobile elements represents the
      DNA transposons, which transpose via excision and the subsequent reinsertion at
      random genomic loci. The increase of their copy number occurs only when the
      transposition event is coupled with the replication. IS630/Tc1/mariner DNA
      transposon superfamily is one of the largest and widely distributed among the
      Class II elements. In this work, we provide a detailed analysis of
      IS630/Tc1/mariner DNA transposons from the Pacific oyster, Crassostrea gigas.
      IS630/Tc1/mariner transposons represented in the genome of the Pacific oyster
      belong to four families, Tc1 (DD34E), mariner (DD34D), pogo (DDxD), and rosa
      (DD41D). More than a half of IS630/Tc1/mariner elements from C. gigas belong to
      Tc1 family. Furthermore, Mariner-31_CGi element was shown to represent a new and
      previously unknown family with DD37E signature. We also discovered the full-size
      transcripts of eight elements from Tc1, mariner, and pogo families, three of
      which can, presumably, retain their transposition activity.

PMID- 30283983
TI  - The ringed esophagus.

PMID- 30283982
TI  - An autologous dendritic cell vaccine polarizes a Th-1 response which is
      tumoricidal to patient-derived breast cancer cells.
AB  - Breast cancer remains one of the leading causes of cancer-associated death
      worldwide. Conventional treatment is associated with substantial toxicity and
      suboptimal efficacy. We, therefore, developed and evaluated the in vitro efficacy
      of an autologous dendritic cell (DC) vaccine to treat breast cancer. We recruited
      12 female patients with stage 1, 2, or 3 breast cancer and matured their DCs with
      autologous tumour-specific lysate, a toll-like receptor (TLR)-3 and 7/8 agonist,
      and an interferon-containing cocktail. The efficacy of the vaccine was evaluated
      by its ability to elicit a cytotoxic T-lymphocyte response to autologous breast
      cancer cells in vitro. Matured DCs (>= 60% upregulation of CD80, CD86, CD83, and
      CCR7) produced high levels of the Th1 effector cytokine, IL12-p70 (1.2 ng/ml; p <
      0.0001), compared to DCs pulsed with tumour lysate, or matured with an interferon
      containing cocktail alone. We further showed that matured DCs enhance antigen
      specific CD8 + T-cell responses to HER-2 (4.5%; p < 0.005) and MUC-1 (19%; p <
      0.05) tetramers. The mature DCs could elicit a robust and dose-dependent antigen
      specific cytotoxic T-lymphocyte response (65%) which was tumoricidal to
      autologous breast cancer cells in vitro compared to T-lymphocytes that were
      primed with autologous lysate loaded-DCs (p < 0.005). Lastly, we showed that the
      mature DCs post-cryopreservation maintained high viability, maintained their
      mature phenotype, and remained free of endotoxins or mycoplasma. We have
      developed a DC vaccine that is cytotoxic to autologous breast cancer cells in
      vitro. The tools and technology generated here will now be applied to a phase
      I/IIa clinical trial.

PMID- 30283981
TI  - The effects of six-day SSRI administration on diurnal cortisol secretion in
      healthy volunteers.
AB  - RATIONALE: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has
      been widely reported in depression, and evidence suggests that selective
      serotonin reuptake inhibitors (SSRIs) might exert their therapeutic effects
      through altering cortisol secretion. OBJECTIVE: This study assessed the effects
      of SSRI administration on diurnal cortisol secretion in healthy volunteers.
      METHODS: Sixty-four healthy men and women were randomised to receive either 10 mg
      escitalopram or placebo for six days in a double-blind fashion. On day six of
      medication, saliva samples were obtained at home for measurement of diurnal
      cortisol parameters (cortisol slope, cortisol awakening response, total daily
      cortisol output). RESULTS: Women receiving escitalopram had significantly steeper
      cortisol slopes across the day compared with those receiving placebo (F(1, 36) =
      7.54, p = 0.009). This alteration in cortisol slope was driven by increases in
      waking cortisol levels (F(1, 35) = 9.21, p = 0.005). Escitalopram did not have
      any significant effect on the cortisol awakening response or the total daily
      cortisol output. CONCLUSIONS: Flattened cortisol slopes have been seen in
      depression. The results of this study suggest that escitalopram might exert its
      therapeutic effect in women in part through correction of a flattened diurnal
      cortisol rhythm.

PMID- 30283984
TI  - Decoupled molecules with binding polynomials of bidegree (n, 2).
AB  - We present a result on the number of decoupled molecules for systems binding two
      different types of ligands. In the case of n and 2 binding sites respectively, we
      show that there are [Formula: see text] decoupled molecules to a generic binding
      polynomial. For molecules with more binding sites for the second ligand, we
      provide computational results.

PMID- 30283985
TI  - Tree-based networks: characterisations, metrics, and support trees.
AB  - Phylogenetic networks generalise phylogenetic trees and allow for the accurate
      representation of the evolutionary history of a set of present-day species whose
      past includes reticulate events such as hybridisation and lateral gene transfer.
      One way to obtain such a network is by starting with a (rooted) phylogenetic tree
      T, called a base tree, and adding arcs between arcs of T. The class of
      phylogenetic networks that can be obtained in this way is called tree-based
      networks and includes the prominent classes of tree-child and reticulation
      visible networks. Initially defined for binary phylogenetic networks, tree-based
      networks naturally extend to arbitrary phylogenetic networks. In this paper, we
      generalise recent tree-based characterisations and associated proximity measures
      for binary phylogenetic networks to arbitrary phylogenetic networks. These
      characterisations are in terms of matchings in bipartite graphs, path partitions,
      and antichains. Some of the generalisations are straightforward to establish
      using the original approach, while others require a very different approach.
      Furthermore, for an arbitrary tree-based network N, we characterise the support
      trees of N, that is, the tree-based embeddings of N. We use this characterisation
      to give an explicit formula for the number of support trees of N when N is
      binary. This formula is written in terms of the components of a bipartite graph.

PMID- 30283986
TI  - Posterior circulation involvement and collateral flow pattern in moyamoya disease
      with the RNF213 polymorphism.
AB  - PURPOSE: Moyamoya disease is a chronic cerebrovascular disorder characterized by
      progressive stenosis of the circle of Willis with a compensatory collateral
      vessel network. Recent studies have identified the ring finger protein 213 gene
      (RNF213) as the unique susceptibility gene for moyamoya disease. The purpose of
      this study was to compare clinical features of moyamoya disease, especially
      angiographic findings, between patients with and without the RNF213 mutation.
      METHODS: Blood samples from 35 patients with moyamoya disease were obtained
      between May 2016 and May 2017. Information on age at the time of diagnosis, sex,
      and initial symptom were obtained via retrospective chart review. Angiographic
      records were evaluated. RESULTS: RNF213 variants were detected in the 28 of 35
      patients (80%), including all pediatric patients (100%) and 18 of 25 adult
      patients (72%) in our cohort. Leptomeningeal collateral flow from posterior to
      anterior circulation was more frequent in the RNF213-negative group than in the
      RNF213-positive group (100% versus 38.9%; p = 0.020). Posterior cerebral arterial
      territorial involvement was more frequently observed in RNF213-positive patients
      than in RNF213-negative patients (50% versus 0%; p = 0.027). CONCLUSIONS: RNF213
      may play a significant role in the development of collateral anastomoses.

PMID- 30283987
TI  - Patterns of Superficial Midfacial Fat Volume Distribution Differ by Age and Body
      Mass Index.
AB  - BACKGROUND: The changes that occur to midfacial fat with increasing age and BMI
      are poorly understood. The aim of this study was to determine how superficial
      cheek fat volume and distribution are differentially predicted by changes in BMI
      versus age. METHODS: We conducted a retrospective observational study of patients
      with facial computed tomography scans. Superficial cheek fat volumes were
      measured, and multiple linear regression analysis was performed to model the
      relationships between cheek fat and corresponding sex, age, and BMI data.
      RESULTS: A total of 109 patients were included in our analysis (51 male, 58
      female). The subjects' ages ranged from 21.7 to 91.1 years with a mean (SD) age
      of 59.7 (15.0) years. The mean (SD) superficial cheek volume of the subjects was
      10.46 (2.57) cc. Female subjects had a significantly greater mean total
      superficial cheek fat volume compared to male subjects (11.18 cc vs. 9.64 cc; P <
      0.001). The results of multiple linear regression analysis indicated that
      together, age, sex, and BMI explained 50.8% of the variance in cheek fat volumes
      (R2 = 0.51, P < 0.001). BMI significantly predicted total cheek fat volume (beta
      = 0.239, P < 0.001), in addition to age (beta = 0.029, P < 0.017) and sex (beta =
      - 1.183, P = 0.001; female = 0, male = 1). Age predicted the greatest gain of fat
      in the caudal subdivision of cheek (beta = 0.015, P < 0.001), whereas BMI
      predicted the greatest gain in the cephalad subdivision (beta = 0.106, P <
      0.001). CONCLUSIONS: Age, sex, and BMI are important predictors of midfacial fat
      volume. This study shows that increases in age and BMI differentially predict the
      distribution of superficial cheek fat. LEVEL OF EVIDENCE IV: This journal
      requires that authors assign a level of evidence to each article. For a full
      description of these Evidence-Based Medicine ratings, please refer to the Table
      of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 30283988
TI  - Lack of Association Between Vitamin D and Hand Grip Strength in Asians: A
      Nationwide Population-Based Study.
AB  - Despite the beneficial role and plausible mechanism of vitamin D on skeletal
      muscle in animal studies, its association in humans remains a controversial issue
      due to inconsistent clinical results, especially in older Asians. This was a
      population-based, cross-sectional study from the Korea National Health and
      Nutrition Examination Surveys, which enrolled 354 men aged >= 50 years and 328
      postmenopausal women. Hand grip strength (HGS) was measured using a digital grip
      strength dynamometer. Low muscle strength was defined based on Korean-specific
      cut-off point of HGS. Serum 25-hydroxyvitamin D [25(OH)D] levels were 19.4 +/-
      6.7 and 17.1 +/- 7.2 ng/mL in men and women, respectively. Among covariates
      including age, body mass index, lifestyle factors, and protein intake, age was
      inversely associated with HGS in both men and women, and protein intake (g/day)
      was positively associated with HGS only in men. However, the independent
      correlation between serum 25(OH)D and HGS was not observed, regardless of gender.
      When subjects were divided into three groups [deficient (25(OH)D < 20 ng/mL;
      63.8%), insufficient (20 <= 25(OH)D < 30 ng/mL; 30.0%), or sufficient (25(OH)D >=
      30 ng/mL; 6.2%)], there was no significant difference in HGS among these groups
      in both men and women. Consistently, serum 25(OH)D was not significantly
      different between subjects with and without low muscle strength, and there was no
      independent association of serum 25(OH)D with the risk of low muscle strength in
      both genders. These findings provide clinical evidence that protective role of
      vitamin D on human muscle metabolism may not be evident at least in older Asians.

PMID- 30283989
TI  - Regulation of the inositol transporter Itr1p by hydrogen peroxide in
      Saccharomyces cerevisiae.
AB  - Myo-inositol is a precursor of several membrane phospholipids and sphingolipids
      and plays a key role in gene regulation in Saccharomyces cerevisiae (S.
      cerevisiae). Here, we tested whether H2O2 was affecting the levels of the
      inositol transporters and thus inositol uptake. In S. cerevisiae cells adapted to
      H2O2 Itr1-GFPp accumulated in the plasma membrane until 20 min, concomitantly
      with an inhibition of its internalization. Exposure to H2O2 did not alter Itr2
      GFPp cellular levels and induced only an 8% decrease at 10 min in the plasma
      membrane. Therefore, decreased inositol intracellular levels are not caused by
      decreased levels of inositol transporters in the plasma membrane. However,
      results show that H2O2 adaptation affects Itr1p turnover and, consequently, H2O2
      adapted yeast cells display an inositol transporter phenotype comparable to cells
      grown in the absence of inositol in growth medium, i.e. accumulation in the
      plasma membrane and decreased degradation.

PMID- 30283990
TI  - Correction to: Limited MHC class II gene polymorphism in the West African
      chimpanzee is distributed maximally by haplotype diversity.
AB  - The authors regret that an error was present in the Fig. 5 of the above article;
      some digits in the DRB allele-designations in Fig. 5 have been lost, and are
      incorrectly presented by only two digits. The correct allele-designations should
      have been four (or six) digits. The correct Figure is now presented correctly.

PMID- 30283992
TI  - Seeking to introduce a pharmacoeconomics framework in Cyprus.

PMID- 30283991
TI  - The Role of AcrAB-TolC Efflux Pumps on Quinolone Resistance of E. coli ST131.
AB  - Escherichia coli ST131 is a cause for global concern because of its high
      multidrug resistance and several virulence factors. In this study, the
      contribution of acrAB-TolC efflux system of E. coli ST131 to fluoroquinolone
      resistance was evaluated. A total of nonrepetitive 111 ciprofloxacin-resistant E.
      coli isolates were included in the study. Multilocus sequence typing was used for
      genotyping. Expressions of acrA, acrB, and TolC efflux pump genes were measured
      by RT-PCR. Mutations in marA, gyrA, parC, and aac(6')-lb-cr positivity were
      studied by Sanger sequencing. Sixty-four (57.7%) of the isolates were classified
      as ST131, and 52 (81.3%) of the ST131 isolates belonged to H30-Rx subclone. In
      ST131, CTX-M 15 positivity (73%) and aac(6')-lb-cr carriage (75%) were
      significantly higher than those in non-ST131 (12.8% and 51%, respectively) (P <
      0.05). The ampicillin-sulbactam (83%) resistance was higher, and gentamicin
      resistance (20%) was lower in ST131 than that in non-ST131 (64% and 55%,
      respectively) (P = 0.001 and P = 0.0002). Numbers of the isolates with MDR or XDR
      profiles did not differ in both groups. Multiple in-dels (up to 16) were recorded
      in all quinolone-resistant isolates. However, marA gene was more overexpressed in
      ST131 compared to that in non-ST131 (median 5.98 vs. 3.99; P = 0.0007). Belonging
      to H30-Rx subclone, isolation site, ciprofloxacin MIC values did not correlate
      with efflux pump expressions. In conclusion, the marA regulatory gene of AcrAB
      TolC efflux pump system has a significant impact on quinolone resistance and
      progression to MDR profile in ST131 clone. Efflux pump inhibitors might be
      alternative drugs for the treatment of infections caused by E. coli ST131 if used
      synergistically in combination with antibiotics.

PMID- 30283993
TI  - Impact of Long-Term Application of Sewage on Soil and Crop Quality in Vertisols
      of Central India.
AB  - Shortfall of rain and the decreased groundwater level force farmers to use poor
      quality water for crop production in developing countries. In this study, the
      quality of agricultural produce and soil health affected by sewage water
      (Patranala) irrigation was evaluated. Sewage sediment, soil and crop samples were
      analyzed for physico-chemical properties. Sewage water found to contain trace
      concentration of heavy metals. However, long-term application of this water for
      crop production could build up a significant amount of trace metals in both soil
      and sediments. The DTPA extractable heavy metals ranged Cu 2.7-7.59, Cd 0.04
      0.06, Pb 1.29-2.05, Cr 0.01-0.04, Ni 0.24-1.03 and Zn 0.63-2.59 mg kg-1 soil. The
      heavy metal risk assessment (hazard quotient, HQ) was calculated and found that
      HQ for these metals in the crops under study was in safe limits. From the study,
      it is concluded that growing vegetables using sewage water of Patranala is safe,
      but periodic monitoring to be carried out to avoid food chain contamination.

PMID- 30283994
TI  - Minimally invasive prostatic urethral lift (PUL) efficacious in TURP candidates:
      a multicenter German evaluation after 2 years.
AB  - INTRODUCTION: Successful outcomes have been reported for the treatment of lower
      urinary tract symptoms (LUTS) with the prostatic urethral lift (PUL) in a number
      of clinical investigations. Our aim was to investigate PUL outcomes in patients
      treated in a day-to-day clinical setting without the rigid exclusion criteria of
      clinical studies. MATERIALS AND METHODS: We investigated the outcome of the PUL
      procedure at five German departments during the initial period when PUL was
      approved for the clinic (10/2012-06/2014). All candidates for transurethral
      resection of the prostate (TURP) received PUL information and were given the
      choice of procedures. The only exclusion criterion was an obstructive median
      lobe. No patients were excluded because of high post-void residual volume (PVR),
      prostate size, retention history or LUTS oral therapy. Maximum urinary flow
      (Qmax), PVR, International Prostate Symptom Score (IPSS) and Quality of Life
      (QOL) were assessed at baseline, 1, 6, 12, and 24 months after surgery. RESULTS:
      Of 212 TURP candidates, 86 choose PUL. A mean of 3.8 (2-7) UroLift implants were
      implanted in patients of 38-85 years with a prostate size of 17-111 ml over 57
      (42-90) min under general or local anesthesia. Thirty-eight (38.4%) patients had
      severe BPH obstruction and would have been denied PUL utilizing previously
      reported study criteria. Within 1 month 74 (86%) reported substantial symptom
      relief with significant improvements in Qmax, PVR, IPSS, and QOL (p < 0.001) that
      was maintained within the follow-up. Sexual function including ejaculation was
      unchanged or improved. No Clavien-Dindo Grad >= 2 was reported postoperatively.
      Eleven (12.8%) patients were retreated over 2 years. Twelve (86%) of 14 patients
      presenting with chronic urinary retention were catheter free at last follow-up.
      CONCLUSION: PUL is a promising surgical technique that may alleviate LUTS, even
      in patients with severe obstruction.

PMID- 30283995
TI  - Can urinary biomarkers replace cystoscopy?
AB  - PURPOSE: Diagnosis and follow-up in patients with non-muscle invasive bladder
      cancer (NMIBC) rely on cystoscopy and urine cytology. The aim of this review
      paper is to give an update on urinary biomarkers and their diagnosis and
      surveillance potential. Besides FDA-approved markers, recent approaches like DNA
      methylation assays, mRNA gene expression assays and cell-free DNA (cfDNA) are
      evaluated to assess whether replacing cystoscopy with urine markers is a
      potential scenario for the future. METHODS: We performed a non-systematic review
      of current literature without time period restriction using the National Library
      of Medicine database ( http://ww.pubmed.gov ). The search included the following
      key words in different combinations: "urothelial carcinoma", "urinary marker",
      "hematuria", "cytology" and "bladder cancer". Further, references were extracted
      from identified articles. The results were evaluated regarding their clinical
      relevance and study quality. RESULTS: Currently, replacing cystoscopy with
      available urine markers is not recommended by international guidelines. For FDA
      approved markers, prospective randomized trials are lacking. Newer approaches
      focusing on molecular, genomic and transcriptomic aberrations are promising with
      good accuracies. Furthermore, these assays may provide additional molecular
      information to guide individualized surveillance strategies and therapy.
      Currently ongoing prospective trials will determine if cystoscopy reduction is
      feasible. CONCLUSION: Urinary markers represent a non-invasive approach for
      molecular characterization of the disease. Although fully replacing cystoscopy
      seems unrealistic in the near future, enhancing the current gold standard by
      additional molecular information is feasible. A reliable classification and
      differentiation between aggressive and nonaggressive tumors by applying DNA,
      mRNA, and cfDNA assays may change surveillance to help reduce cystoscopies.

PMID- 30283996
TI  - Analysis of factors affecting re-admission after retrograde intrarenal surgery
      for renal stone.
AB  - PURPOSE: To investigate the factors associated with hospital readmission (HR)
      after retrograde intrarenal surgery (RIRS) among renal stone patients. METHODS:
      The study included patients who underwent RIRS from June 2011 to December 2017.
      Patients who were readmitted due to surgery-related complications were evaluated
      retrospectively. Patient demographics including age, medical comorbidity, body
      mass indices, ASA score, perioperative parameters and stone factors were compared
      with total cohorts. HR was defined as visits to the Emergency Room or unplanned
      admission within 30 days after discharge. The factors affecting HR rates were
      analyzed using uni- and multi-variate analyses. RESULTS: A total of 572 patients
      were enrolled into the study. The mean age was 57.6 +/- 14.1 years and the mean
      stone diameter was 13.4 +/- 6.2 mm. The mean complication rate was 6.1% and the
      median hospitalization time was 2.1 +/- 3.4 days. HR occurred in 20 patients
      (3.5%). Compared to non-admission patients, readmitted patients had a higher rate
      of bilateral RIRS (20.0% vs 12.2%, p = 0.035), number of stones (4.65 vs 2.2, p =
      0.041) and higher stone complexity score (4.15 vs 2.11, p = 0.003). Multivariate
      analysis showed bilateral RIRS (OR 1.091, p = 0.031) and stone complexity (OR
      1.405, p = 0.003) were significant factors to predict re-admission after RIRS.
      CONCLUSION: Patients with complex renal stones or those who underwent bilateral
      RIRS were more likely to have a higher rate of re-admission. Proper perioperative
      management to prevent complications should be planned based on these predictive
      factors.

PMID- 30283997
TI  - A signal-on electrochemiluminescence sensor for clenbuterol detection based on
      zinc-based metal-organic framework-reduced graphene oxide-CdTe quantum dot
      hybrids.
AB  - Clenbuterol (CLB) is harmful to human health when used long term, and it has been
      listed by the World Anti-Doping Agency (WADA). In this work, a novel zinc-based
      metal-organic frameworks-reduced graphene oxide-CdTe quantum dots (ZnMOF-RGO-CdTe
      QDs) hybrid was used to construct an electrochemiluminescence (ECL) sensor for
      detecting CLB. CdTe QDs, loaded by RGO, exhibited an enhanced ECL signal. In
      addition, the ZnMOFs catalyzed OH* generation by coreactant H2O2, which further
      strengthened the ECL signal of the CdTe QDs. The integration of ZnMOFs and RGO
      CdTe QDs endowed the sensor with high sensitivity for CLB detection. The
      intensity of the ECL signal increased as the concentration of CLB increased. The
      linear range of CLB detection was 3.0 * 10-13 M to 6.0 * 10-10 M, and the
      detection limit was estimated to be 1.0 * 10-13 M. Furthermore, the sensor
      displayed a good repeatability and stability. The ZnMOF-RGO-CdTe QD hybrids
      described in this study provide a foundation for the development of new methods
      of detecting CLB. Graphical abstract ?.

PMID- 30283998
TI  - Non-invasive monitoring of blood glucose using optical methods for skin
      spectroscopy-opportunities and recent advances.
AB  - Diabetes mellitus is a widespread disease with greatly rising patient numbers
      expected in the future, not only for industrialized countries but also for
      regions in the developing world. There is a need for efficient therapy, which can
      be via self-monitoring of blood glucose levels to provide tight glycemic control
      for reducing the risks of severe health complications. Advancements in diabetes
      technology can nowadays offer different sensor approaches, even for continuous
      blood glucose monitoring. Non-invasive blood glucose assays have been promised
      for many years and various vibrational spectroscopy-based methods of the skin are
      candidates for achieving this goal. Due to the small spectral signatures of the
      glucose hidden among a largely variable background, the largest signal-to-noise
      ratios and multivariate calibration are essential to provide the method
      applicability for self-monitoring of blood glucose. Besides multiparameter
      approaches, recently presented devices based on photoplethysmography with
      wavelengths in the visible and near-infrared range are evaluated for their
      potential of providing reliable blood glucose concentration predictions.
      Graphical abstract ?.

PMID- 30283999
TI  - Photoelectrochemical immunoassay of lipoprotein-associated phospholipase A2 via
      plasmon-enhanced energy transfer between gold nanoparticles and CdS QDs/g-C3N4.
AB  - A facile and feasible photoelectrochemical (PEC) immunoassay based on plasmon
      enhanced energy transfer between gold nanoparticles (AuNPs) and CdS quantum dots
      (QDs)/g-C3N4 nanosheets was developed for the ultrasensitive detection of
      lipoprotein-associated phospholipase A2 (Lp-PLA2). To construct such a sensing
      platform, the immunosensor was prepared by immobilizing Lp-PLA2 on a CdS QDs/g
      C3N4-modified electrode. A competitive-type immunoreaction was utilized for Lp
      PLA2 detection, with AuNP-labeled anti-Lp-PLA2 antibody used as the competitor.
      Introducing AuNPs with the specific antibody for the antigen target Lp-PLA2 led
      to heavy quenching of the photocurrent of CdS QDs/g-C3N4 due to the plasmon
      enhanced energy transfer between AuNPs and CdS QDs. The quenching efficiency
      decreased with increasing target Lp-PLA2 concentration. Under optimal conditions,
      the PEC immunosensor presented a good photocurrent response to the target Lp-PLA2
      in the dynamic linear range of 0.01-300 ng mL-1, with a low detection limit of
      5.3 pg mL-1. Other biomarkers and natural enzymes did not interfere with response
      of this system. The reproducibility and accuracy of this method for the analysis
      of human serum specimens were evaluated, and the results given by the method
      developed here were found to closely correspond to the results obtained with
      commercial Lp-PLA2 ELISA kits. Importantly, this protocol offers promise for the
      development of exciton-plasmon interaction-based PEC detection systems. Graphical
      abstract ?.

PMID- 30284000
TI  - Selective extraction of 3,4-dihydroxybenzoic acid in Ilex chinensis Sims by
      meticulous mini-solid-phase microextraction using ternary deep eutectic solvent
      based molecularly imprinted polymers.
AB  - A ternary deep eutectic solvent (TDES) was used as both template and functional
      monomer in the synthesis of TDES-based molecularly imprinted polymers (TDES
      MIPs). A meticulous miniaturized solid-phase microextraction (mini-SPME) method
      followed by high-performance liquid chromatography (HPLC) were used for the
      optimal speciation of 3,4-dihydroxybenzoic acid (3,4-DHBA) in the needle of a
      syringe system with response surface methodology (RSM). Under the optimal
      conditions for the determination of 3,4-DHBA (amount of adsorbent (2 mg), sample
      volume (1 mL), cycles for adsorption and desorption (6)), the actual extraction
      amount was 8.46 MUg g-1. The limits of detection (LODs, S/N = 3) for 3,4-DHBA in
      Ilex chinensis Sims were 0.26-0.31 MUg mL-1, and the intra-day and inter-day
      precision (relative standard deviations, n = 4) after spiking with 5 MUg mL-1,
      100 MUg mL-1, and 200 MUg mL-1 were both less than 4.21%. The meticulous method
      (TDES-MIP-mini-SPME) combined with RSM offers a significant advance over existing
      methods, because of the meticulous operation and excellent selectivity of 3,4
      DHBA from complex samples. Graphical abstract ?.

PMID- 30284001
TI  - Os acetabuli and femoro-acetabular impingement: aetiology, incidence, treatment,
      and results.
AB  - PURPOSE: The purpose of this study was to investigate the pathogenesis, the
      incidence, and the results of arthroscopic treatment of os acetabuli (OSA) in a
      group of patients with diagnosis of femoro-acetabular impingement (FAI). METHODS:
      We retrospectively analyzed the full documentation of 294 hips in 273 patients
      (21 bilateral) operated for FAI through hip arthroscopy. We reviewed all
      radiographs and arthro-MRI in order to identify the incidence of OSA. All
      patients with OSA were then assessed with a modified Harris hip score (MHHS) pre
      operatively and at the final follow-up. RESULTS: Twenty-one patients (7.7%), 20
      (95%) of them were male, were diagnosed with concomitant FAI and os acetabuli. In
      21 cases, OSA was excised and FAI was treated with rim trimming, femoral
      osteoplasty, or both. In one case, a large OSA fragment was fixed with a 4 mm
      screw avoiding an acetabular uncoverage if excised. The average follow-up was 31
      months (range from 6 to 69 months). The MHHS showed an improvement from a pre
      operative MHHS of 57.5 (range from 39 to 82) to 95 (range from 73 to 100).
      CONCLUSIONS: Os acetabuli is not uncommon and certainly associated with FAI and
      male gender. The etiology is probably microtraumatic. The arthroscopic OSA
      removal or fixation and concomitant FAI treatment showed very good results.
      Interestingly, these outcomes seem better than FAI treatment alone. Further
      studies with a wider number of patients and a longer follow-up are needed to
      confirm these results and understand the real role of OSA in this setting.

PMID- 30284002
TI  - Bone mineral density as a marker of hip implant longevity: a prospective
      assessment of a cementless stem with dual-energy X-ray absorptiometry at twenty
      years.
AB  - PURPOSE: Bone remodeling around the femoral component after total hip
      arthroplasty (THA) is considered to be an important factor in long-term stability
      and seems to be strictly related to the stem design, coating, and fixation.
      Stress shielding, micro-movement, and high intra-articular fluid pressure might
      activate macrophages and osteoclasts, causing progressive bone density decreases.
      Here we analyze the bone mineral density (BMD) around a cementless femoral stem
      during a 20-year period to better understand the adaptive bone changes around
      such implants during long-term follow-up. METHODS: In this retrospective study,
      14 patients treated by THA were reviewed from a cohort of 84. Clinical evaluation
      with Harris Hip Score and radiographic assessment were performed throughout a 20
      year follow-up. To evaluate the bone remodeling around the stem, we monitored the
      femoral BMD in four regions of interest with a dual-energy X-ray absorptiometry
      (DEXA) post-operatively and at one, two, three, five and 20 years of follow-up.
      RESULTS: The main BMD changes between the post-operative examination and the 20
      year follow-up varied between + 11.19% and + 24.30%. Patients with signs of
      loosening, low Harris Hip Scores, and pain showed decreasing BMD values.
      CONCLUSIONS: The correlation between the clinical result and BMD values could
      suggest DEXA results as a predictor of implant loosening or longevity.

PMID- 30284003
TI  - Primary cementless total knee arthroplasty with or without stem extension: a
      matched comparative study of ninety eight standard stems versus ninety eight long
      stems after more than ten years of follow-up.
AB  - INTRODUCTION: Using a cementless fixation for total knee arthroplasty (TKA) is
      controversial. We hypothesized that cementless tibial base plate with a monoblock
      long stem (MLS) would provide secure tibial alignment and stable fixation when
      bone conditions were considered as poor for a cementless fixation. The purpose of
      this study was to compare the mean eight year survivorship of cementless standard
      keels (SK) vs cementless MLS. MATERIAL METHODS: We report a matched series of 98
      cases of SK and 98 cases of MLS in patients with poor bone conditions. The two
      cohorts were statistically compared. Revision for tibial loosening was used as
      the endpoint in the survivorship analysis. RESULTS: We recorded two cases of
      tibial loosening and three cases of bipolar loosening in the SK group (0% MLS vs
      5% SK). No tibial loosening occurred in the MLS group (statistically
      significant). No tibial periprosthetic or intra-operative fractures occurred in
      either group. The survivorship at eight years of follow-up was 95.6% in the SS
      cohort vs 100% in the MLS cohort using revision for tibial loosening as the
      endpoint. DISCUSSION: This study was not randomized. Its strength was that it
      took into account the comparative midterm outcomes of a matched cohort of
      patients implanted with two types of cementless components in the same bone
      conditions. We did not record any tibial loosening in the MLS group. Using long
      stems has been criticized but we did not observe any adverse reactions and no
      intra-operative tibial fracture occurred. CONCLUSION: MLS improves the alignment
      and fixation of cementless TKA. This is a safe solution when bone conditions are
      poor or modified by previous surgery.

PMID- 30284004
TI  - Arthroscopic synovectomy of the knee joint for rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the effect of knee arthroscopic synovectomy (AS) on the
      disease activity, quality-of-life (QoL), and the functional status of patients
      with rheumatoid arthritis (RA). MATERIALS AND METHODS: A retrospective analysis
      was conducted on the outcomes of AS performed on 138 RA patients; pre-surgery
      assessments were done using Disease Activity score (DAS 28) and Routine
      Assessment of Patient Index Data ZE (RAPID-3) on a multidimensional health
      assessment questionnaire for disease activity, EuroQol-5D (EQ-5D) and the Short
      Form Medical Outcomes Study (SF-36) for quality of life, and the Health
      Assessment Questionnaire (HAQ) for functional status. The pain response to SA was
      measured by a visual analogue score (VAS) and the Knee Society Score (KSS).
      RESULTS: All parameters assessed in the study showed significant positive
      changes: the activity of the disease decreased, and patients' functional status
      and QoL improved. CONCLUSION: AS is effective treatment for recurrent synovitis
      of the knee in RA patients. This technique improves the functional status of
      patients and their quality of life and reduces the activity of the disease.

PMID- 30284005
TI  - Differential diagnosis of perinatal hypophosphatasia: radiologic perspectives.
AB  - Perinatal hypophosphatasia (HPP) is a rare, potentially life-threatening,
      inherited, systemic metabolic bone disease that can be difficult to recognize in
      utero and postnatally. Diagnosis is challenging because of the large number of
      skeletal dysplasias with overlapping clinical features. This review focuses on
      the role of fetal and neonatal imaging modalities in the differential diagnosis
      of perinatal HPP from other skeletal dysplasias (e.g., osteogenesis imperfecta,
      campomelic dysplasia, achondrogenesis subtypes, hypochondrogenesis, cleidocranial
      dysplasia). Perinatal HPP is associated with a broad spectrum of imaging findings
      that are characteristic of but do not occur in all cases of HPP and are not
      unique to HPP, such as shortening, bowing and angulation of the long bones, and
      slender, poorly ossified ribs and metaphyseal lucencies. Conversely, absent
      ossification of whole bones is characteristic of severe lethal HPP and is
      associated with very few other conditions. Certain features may help distinguish
      HPP from other skeletal dysplasias, such as sites of angulation of long bones,
      patterns of hypomineralization, and metaphyseal characteristics. In utero
      recognition of HPP allows for the assembly and preparation of a multidisciplinary
      care team before delivery and provides additional time to devise treatment
      strategies.

PMID- 30284006
TI  - Non-contrast-enhanced magnetic resonance angiography for detecting crossing renal
      vessels in infants and young children: comparison with contrast-enhanced
      angiography and surgical findings.
AB  - BACKGROUND: Knowing that ureteropelvic junction obstruction is due to a crossing
      renal vessel is essential in choosing the appropriate surgical treatment.
      OBJECTIVE: To evaluate the diagnostic accuracy of non-contrast magnetic resonance
      (MR) angiography in identifying crossing renal vessels in children younger than 4
      years old with unilateral hydronephrosis. MATERIALS AND METHODS: A retrospective
      review of preoperative MR urography of children with unilateral hydronephrosis
      was conducted by two independent readers. The presence or absence of crossing
      renal vessels was identified and compared with surgical findings. RESULTS: Twenty
      nine patients were included. The disagreement between MR angiography with and
      without contrast enhancement in detecting a crossing renal vessel was 8%. The
      disagreement between non-contrast-enhanced MR and surgical findings was 17%. The
      disagreement between contrast-enhanced MR angiography and surgical findings was
      25%. The balanced triggered angiography without contrast enhancement had a
      sensitivity of 70% (95% confidence interval [CI]: 35-93%) and a specificity of
      93% (95% CI: 66-100%). Contrast-enhanced MR angiography had a sensitivity of 56%
      (95% CI: 21-86%) and a specificity of 91%. (95% CI: 59-100%). CONCLUSION: MR
      without contrast enhancement may be a reliable, valid and safe alternative to
      contrast-enhanced MR angiography for identifying crossing renal vessels.

PMID- 30284007
TI  - More tendon degeneration in patients with shoulder osteoarthritis.
AB  - PURPOSE: Tendon disorders are a major problem in the general population. It is
      known that rotator cuff tendinopathy contributes to osteoarthritis (OA) of the
      shoulder. The aim of the study was to analyse the presence of tendinopathy in
      patients with shoulder OA and an intact rotator cuff, using a multimodal
      approach. METHODS: Thirteen consecutive patients median age 67 (52-84) years,
      with OA of the shoulder, and 13 consecutive control patients, with a fracture of
      the proximal humerus, median age 70 (51-84) years, underwent an open biopsy
      procedure from the biceps and subscapularis tendon in conjunction with shoulder
      arthroplasty. In addition to a macroscopic evaluation, the samples underwent
      histologic, morphologic and ultrastructural analyses in light and transmission
      electron microscopy. RESULTS: Macroscopic degeneration was found in 15 of 26
      specimen in the OA group but in seven of 25 in the control group (p = 0.048). The
      histologic analysis revealed a non-significant difference for the total
      degeneration score (TDS) between the study groups. The morphologic evaluation of
      the samples revealed that the OA group had significantly more samples with non
      homogeneous extracellular matrix (ECM), (p = 0.048). Ultrastructurally, the OA
      group revealed a significantly larger fibril diameter in the biceps tendon (p <
      0.0001) but not in the subscapularis tendon compared with the control group.
      CONCLUSION: A significantly worse macroscopic appearance and significantly more
      morphologically inhomogeneous ECM, indicating more tendon degeneration, were
      found in the OA group compared with the control group. This indicates that it
      could be beneficial to treat the tendinosis in an early stage to decrease
      symptoms from the OA. STUDY DESIGN: Level of evidence, III.

PMID- 30284008
TI  - Degenerative isolated cartilage defects of the patellofemoral joint are
      associated with more severe symptoms compared to trauma-related defects: results
      of the German Cartilage Registry (KnorpelRegister DGOU).
AB  - PURPOSE: The purpose of this study was to utilize data from the German Cartilage
      Registry (KnorpelRegister DGOU) to examine the hypothesis that degenerative
      cartilage defects of the patellofemoral joint are associated with more severe
      clinical symptoms compared to trauma-related defects. METHODS: All patients with
      isolated focal cartilage defects of the patellofemoral joint registered in the
      German Cartilage Registry until May 2017 were included in the study. Patients
      with previous surgery of the ipsilateral knee were excluded. Baseline data
      including etiology (traumatic, degenerative), size, location and ICRS grade of
      the cartilage defects as well as the duration of symptoms were analyzed. Clinical
      symptoms were evaluated by means of the numeric analog scale (NAS) for pain and
      the Knee injury and Osteoarthritis Outcome Score (KOOS). Group comparisons were
      performed using the Mann-Whitney-U test along with the Chi-squared test and
      Fisher's exact test. A bivariate correlation analysis and a multivariable linear
      regression analysis were performed to investigate the association between the
      defect characteristics and the clinical scores. RESULTS: A total of 423 patients
      (203 traumatic and 220 degenerative defects) were included. Isolated degenerative
      cartilage defects were found to have significantly more trochlear locations (28%
      vs. 18%; p = 0.006), significantly less ICRS grade 4 lesions (50% vs. 73%; p =
      0.002) and a significantly smaller defect size [median 300 (IQR 105-400) vs. 300
      (200-400) mm2] when compared to those from traumatic etiology. Traumatic defects
      showed significantly better KOOS-ADL [77 (60-90) vs. 69 (56-82); p = 0.005], KOOS
      pain [69 (56-81) vs. 61 (47-75); p = 0.001] and NAS [2 (1-5) vs. 4 (1-6); p =
      0.005] scores compared to degenerative defects. The correlation analysis revealed
      only weak correlations between the quantitative defect characteristics and
      clinical scores. CONCLUSIONS: Degenerative isolated cartilage defects in the
      patellofemoral joint are associated with more severe clinical symptoms in
      comparison to trauma-related defects. Additionally, they show a larger variance
      regarding their location with more trochlear defects. LEVEL OF EVIDENCE: III.

PMID- 30284009
TI  - Two-dimensional measurement misidentifies alignment outliers in total knee
      arthroplasty: a comparison of two- and three-dimensional measurements.
AB  - PURPOSE: Two-dimensional (2D) and three-dimensional (3D) measurements of
      prosthetic alignment and "outliers" after total knee arthroplasty (TKA) might not
      necessarily be comparable. The aim of this study was to compare the use of 2D and
      3D measurements in the identification of prosthetic alignment and outliers after
      TKA. METHODS: This cross-sectional study included 159 consecutive TKAs. All
      patients underwent plain radiography, fluoroscopy-guided radiography, and
      computed tomography after TKA. The same baseline was used for 2D and 3D
      measurements. The reliability of prosthetic alignment and outlier identification
      (> 3 degrees  from neutral alignment) was compared between the 2D and 3D
      measurements. RESULTS: The mean prosthetic alignment and rate of outliers were
      not significantly different the between 2D and 3D measurements. The inter- and
      intra-observer reliabilities were higher for the 3D measurements than for the 2D
      measurements. The agreement between 2D and 3D measurements in outlier
      identification was poor, except for femoral coronal alignment. Cohen's kappa
      coefficients were 0.19 in femoral sagittal (poor), 0.02 in tibial coronal (poor),
      and 0.10 in tibial sagittal (poor) on plain radiography. The values were 0.23 in
      tibial coronal (poor) and 0.002 in tibial sagittal (poor) on fluoroscopy-guided
      radiography. CONCLUSIONS: The agreement between 2D and 3D measurements in the
      identification of outliers was poor, even on fluoroscopy-guided radiography.
      Since 2D measurements have an inherent risk of misidentifying alignment outliers,
      this finding is clinically relevant. To properly analyze the correlation between
      outliers and clinical results, such as longevity, patient satisfaction, and
      patient-reported outcome, 3D measurements for prosthetic alignment are desirable.
      LEVEL OF EVIDENCE: III.

PMID- 30284010
TI  - Ultrasonography has high positive predictive value for medial epicondyle lesions
      among adolescent baseball players.
AB  - PURPOSE: Only few studies have investigated medial epicondyle (MEC) lesions,
      particularly in the 12-18 age group. To the best of our knowledge, no study has
      compared ultrasonography (US), radiography and magnetic resonance imaging (MRI)
      in detecting MEC lesions. The aims of this study were to examine the value of US
      for detecting MEC lesions and to investigate correlations among diagnostic tools.
      METHODS: A prospective, comparative study was performed. Young baseball players
      from southern Taiwan were recruited, and basic characteristics, as well as
      passive range of motion (pROM) of the upper extremities, were recorded. Screening
      US was performed to identify MEC lesions, and players with MEC lesions received
      follow-up plain radiography and MRI. RESULTS: A total of 299 young baseball
      players were screened using US, and 28 of 299 players with possible MEC lesions
      were identified with a positive predictive value (PPV) of 88% according to MRI
      findings. The MEC lesions were primarily comprised of unfused ossicles and bony
      fragmentation. Other diagnoses, including UCL strain and medial epicondylitis,
      were also found by MRI in players with abnormal US screening results. The pROM of
      shoulder external rotation (ER) of the throwing hand was significantly reduced in
      players with MEC lesions (p = 0.006). CONCLUSIONS: Bony cortical discontinuity or
      fragmentation over the MEC warrants further research, and US provides good PPV
      for types of MEC lesions. Decreased shoulder ER may relate to MEC lesions and
      should be taken into consideration. The use of US may facilitate early detection
      and intervention. LEVEL OF EVIDENCE: IV, Cross-sectional study.

PMID- 30284011
TI  - Bioconversion of green volatiles in okara (soybean residue) into esters by
      coupling enzyme catalysis and yeast (Lindnera saturnus) fermentation.
AB  - Okara (soybean residue), a by-product from soymilk and tofu production, has a
      green, grassy off odour as it contains a large amount of aldehydes. This work
      investigated the rate-limiting enzyme(s) in the formation of aldehydes in okara
      and the pathways leading to their bioconversion into fruity, pleasant-smelling
      esters by the yeast Lindnera saturnus. Lipase and hydroperoxide lyase were shown
      to be rate-limiting enzymes while endogenous soy lipoxygenase was also crucial
      for the production of aldehydes in okara. Subsequent fermentation of okara by L.
      saturnus increased the amount of esters by about 70 times to 165-277 MUg/g dried
      okara. The generation of C7 esters followed our hypothesised pathway, while that
      for C6 esters was mainly affected by L. saturnus. This study presents a simple
      and inexpensive one-pot setup for the natural bio-production of esters from
      okara.

PMID- 30284012
TI  - Analysis of differentially upregulated proteins in ptsHIcrr- and rppH- mutants in
      Escherichia coli during an adaptive laboratory evolution experiment.
AB  - The previous deletion of the cytoplasmic components of the phosphotransferase
      system (PTS) in Escherichia coli JM101 resulted in the PTS- derivative strain
      PB11 with severely impaired growth capability in glucose as the sole carbon
      source. Previous adaptive laboratory evolution (ALE) experiment led to select a
      fast-growing strain named PB12 from PB11. Comparative genome analysis of PB12
      showed a chromosomal deletion, which result in the loss of several genes
      including rppH which codes for the RNA pyrophosphohydrolase RppH, involved in the
      preparation of hundreds of mRNAs for further degradation by RNase E. Previous
      inactivation of rppH in PB11 (PB11rppH-) improved significantly its growing
      capabilities and increased several mRNAs respect its parental strain PB11. These
      previous results led to propose to the PB11rppH- mutant as an intermediate
      between PB11 and PB12 strains merged during the early ALE experiment. In this
      contribution, we report the metabolic response to the PTS- and rppH- mutations in
      the deep of a proteomic approach to understanding the relevance of rppH-
      phenotype during an ALE experiment. Differentially upregulated proteins between
      the wild-type JM101/PB11, PB11/PB11rppH-, and PB11/PB12 comparisons led to
      identifying 45 proteins between strain comparisons. Downregulated or upregulated
      proteins in PB11rppH- were found expressed at an intermediate level with respect
      to PB11 and PB12. Many of these proteins were found involved in non-previously
      metabolic traits reported in the study of the PTS- strains, including glucose,
      amino acids, ribose transport; amino acid biosynthesis; NAD biosynthesis/salvage
      pathway, biosynthesis of Ac-CoA precursors; detoxification and degradation
      pathways; stress response; protein synthesis; and possible mutator activities
      between comparisons. No changes were found in the expression of galactose
      permease GalP, previously proposed as the primary glucose transporter in the
      absence of PTS selected by the PTS- derivatives during the ALE experiment. This
      result suggests that the evolving PTS- population selected other transporters
      such as LamB, MglB, and ManX instead of GalP for glucose uptake during the early
      ALE experiment. Analysis of the biological relevance of the metabolic traits
      developed by the studied strains provided valuable information to understand the
      relevance of the rppH- mutation in the PTS- background during an ALE experiment
      as a strategy for the selection of valuable phenotypes for metabolic engineering
      purposes.

PMID- 30284013
TI  - 2-Deoxy-D-ribose-5-phosphate aldolase (DERA): applications and modifications.
AB  - 2-Deoxy-D-ribose-5-phosphate aldolase (DERA) is a class I aldolase that offers
      access to several building blocks for organic synthesis. It catalyzes the
      stereoselective C-C bond formation between acetaldehyde and numerous other
      aldehydes. However, the practical application of DERA as a biocatalyst is limited
      by its poor tolerance towards industrially relevant concentrations of aldehydes,
      in particular acetaldehyde. Therefore, the development of proper experimental
      conditions, including protein engineering and/or immobilization on appropriate
      supports, is required. The present review is aimed to provide a brief overview of
      DERA, its history, and progress made in understanding the functioning of the
      enzyme. Furthermore, the current understanding regarding aldehyde resistance of
      DERA and the various optimizations carried out to modify this property are
      discussed.

PMID- 30284014
TI  - Genome-wide profiling of histone H3K27 acetylation featured fatty acid signalling
      in pancreatic beta cells in diet-induced obesity in mice.
AB  - AIMS/HYPOTHESIS: Epigenetic regulation of gene expression has been implicated in
      the pathogenesis of obesity and type 2 diabetes. However, detailed information,
      such as key transcription factors in pancreatic beta cells that mediate
      environmental effects, is not yet available. METHODS: To analyse genome-wide cis
      regulatory profiles and transcriptome of pancreatic islets derived from a diet
      induced obesity (DIO) mouse model, we conducted chromatin immunoprecipitation
      coupled with high-throughput sequencing (ChIP-Seq) of histone H3 lysine 27
      acetylation (histone H3K27ac) and high-throughput RNA sequencing. Transcription
      factor-binding motifs enriched in differential H3K27ac regions were examined by
      de novo motif analysis. For the predicted transcription factors, loss of function
      experiments were performed by transfecting specific siRNA in INS-1, a rat beta
      cell line, with and without palmitate treatment. Epigenomic and transcriptional
      changes of possible target genes were evaluated by ChIP and quantitative RT-PCR.
      RESULTS: After long-term feeding with a high-fat diet, C57BL/6J mice were obese
      and mildly glucose intolerant. Among 39,350 islet cis-regulatory regions, 13,369
      and 4610 elements showed increase and decrease in ChIP-Seq signals, respectively,
      significantly associated with global change in gene expression. Remarkably,
      increased H3K27ac showed a distinctive genomic localisation, mainly in the
      proximal-promoter regions, revealing enriched elements for nuclear respiratory
      factor 1 (NRF1), GA repeat binding protein alpha (GABPA) and myocyte enhancer
      factor 2A (MEF2A) by de novo motif analysis, whereas decreased H3K27ac was
      enriched for v-maf musculoaponeurotic fibrosarcoma oncogene family protein K
      (MAFK), a known negative regulator of beta cells. By siRNA-mediated knockdown of
      NRF1, GABPA or MEF2A we found that INS-1 cells exhibited downregulation of fatty
      acid beta-oxidation genes in parallel with decrease in the associated H3K27ac.
      Furthermore, in line with the epigenome in DIO mice, palmitate treatment caused
      increase in H3K27ac and induction of beta-oxidation genes; these responses were
      blunted when NRF1, GABPA or MEF2A were suppressed. CONCLUSIONS/INTERPRETATION:
      These results suggest novel roles for DNA-binding proteins and fatty acid
      signalling in obesity-induced epigenomic regulation of beta cell function. DATA
      AVAILABILITY: The next-generation sequencing data in the present study were
      deposited at ArrayExpress. RNA-Seq: Dataset name: ERR2538129 (Control),
      ERR2538130 (Diet-induced obesity) Repository name and number: E-MTAB-6718 - RNA
      Seq of pancreatic islets derived from mice fed a long-term high-fat diet against
      chow-fed controls. ChIP-Seq: Dataset name: ERR2538131 (Control), ERR2538132 (Diet
      induced obesity) Repository name and number: E-MTAB-6719 - H3K27ac ChIP-Seq of
      pancreatic islets derived from mice fed a long-term high-fat diet (HFD) against
      chow-fed controls.

PMID- 30284015
TI  - Clinical outcomes of an integrated primary-secondary model of care for
      individuals with complex type 2 diabetes: a non-inferiority randomised controlled
      trial.
AB  - AIMS/HYPOTHESIS: The aim of the study was to determine if a Beacon model of
      integrated care utilising general practitioners (GPs) with special interests
      could achieve similar clinical outcomes to a hospital-based specialist diabetes
      outpatient clinic. METHODS: This pragmatic non-inferiority multisite randomised
      controlled trial assigned individuals with complex type 2 diabetes to care
      delivered by a Beacon clinic or to usual care delivered by a hospital outpatient
      department, in a 3:1 ratio. Owing to the nature of the study, researchers were
      only blinded during the allocation process. Eligible participants were aged 18 or
      over, had been referred by their usual GP to the hospital central referral hub
      with type 2 diabetes and had been triaged to be seen within 30 or 90 days. The
      intervention consisted of diabetes management in primary care by GPs with a
      special interest who had been upskilled in complex diabetes under the supervision
      of an endocrinologist. The primary outcome was HbA1c at 12 months post
      recruitment. The non-inferiority margin was 4.4 mmol/mol (0.4%). Both per
      protocol and intention-to-treat analyses are reported. RESULTS: Between 27
      November 2012 and 14 July 2015, 352 individuals were recruited and 305 comprised
      the intention-to-treat sample (71 in usual care group and 234 in the Beacon model
      group). The Beacon model was non-inferior to usual care for both the per-protocol
      (difference -0.38 mmol/mol [95% CI -4.72, 3.96]; -0.03% [95% CI -0.43, 0.36]) and
      the intention-to-treat (difference -1.28 mmol/mol [95% CI -5.96, 3.40]; -0.12%
      [95% CI -0.55, 0.31]) analyses. Non-inferiority was sustained in a sensitivity
      analysis at 12 months. There were no statistically or clinically significant
      differences in the secondary outcomes of BP, lipids or quality of life as
      measured by the 12 item short-form health survey (SF-12v2) and the diabetes
      related quality of life (DQoL-Brief) survey. Safety indicators did not differ
      between groups. Participant satisfaction on the eight-item client satisfaction
      questionnaire (CSQ-8) was good in both groups, but scores were significantly
      higher in the Beacon model group than the usual care group (mean [SD] 28.4 [4.9]
      vs 25.6 [4.9], respectively, p < 0.001). CONCLUSIONS/INTERPRETATION: In
      individuals with type 2 diabetes, a model of integrated care delivered in the
      community by GPs with a special interest can safely achieve clinical outcomes
      that are not inferior to those achieved with gold-standard hospital-based
      specialist outpatient clinics. Individuals receiving care in the community had
      greater satisfaction. Further studies will determine the cost of delivering this
      model of care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry ACTRN12612000380897 FUNDING: The study was funded by the Australian
      National Health and Medical Research Council (GNT1001157).

PMID- 30284016
TI  - Detection and quantification of beta cells by PET imaging: why clinical
      implementation has never been closer.
AB  - In this issue of Diabetologia, Alavi and Werner ( https://doi.org/10.1007/s00125
      018-4676-1 ) criticise the attempts to use positron emission tomography (PET) for
      in vivo imaging of pancreatic beta cells, which they consider as 'futile'. In
      support of this strong statement, they point out the limitations of PET imaging,
      which they believe render beta cell mass impossible to estimate using this
      method. In our view, the Alavi and Werner presentation of the technical
      limitations of PET imaging does not reflect the current state of the art, which
      leads them to questionable conclusions towards the feasibility of beta cell
      imaging using this approach. Here, we put forward arguments in favour of
      continuing the development of innovative technologies enabling in vivo imaging of
      pancreatic beta cells and concisely present the current state of the art
      regarding putative technical limitations of PET imaging. Indeed, far from being a
      'futile' effort, we demonstrate that beta cell imaging is now closer than ever to
      becoming a long-awaited clinical reality.

PMID- 30284017
TI  - The perfusion index is a useful screening tool for peripheral artery disease.
AB  - The number of people with peripheral artery disease (PAD) has been increasing
      globally; therefore, it is important to explore more options to screen patients
      who are at a risk of developing PAD. The perfusion index (PI) represents the
      degree of circulation through the peripheral tissues and is measured
      noninvasively. We investigated the correlation between the PI and ankle-brachial
      index (ABI) to explore whether the PI could be used a screening tool for PAD.
      This cross-sectional study included 390 patients. We measured the ABI and PI for
      all patients. The median ABI value was 1.06 (0.92-1.13); the PI was 1.7% (0.9
      3.5). The PI was higher in men than in women (P < 0.0001). The PI was positively
      correlated with the estimated glomerular filtration rate and ABI in both men and
      women. The sensitivity and specificity of the PI to predict PAD (ABI <=0.9) were
      90.0% and 80.3%, respectively, and the cutoff PI value was 1.5% in men. The
      sensitivity and specificity of the PI to predict PAD were 82.1% and 79.2%,
      respectively, and the cutoff PI value was 1.1% in women. PI could be a reliable
      screening tool for diagnosing PAD because it does not restrict the patient's
      mobility, can be completed in a short time period, and is associated with reduced
      costs.

PMID- 30284018
TI  - Differential effect of concomitant antidiabetic agents on carotid
      atherosclerosis: a subgroup analysis of the PROLOGUE study.
AB  - Accumulated evidence shows that some antidiabetic agents attenuate the
      progression of carotid atherosclerosis assessed as intima-media thickness (IMT).
      Although some studies have demonstrated an inhibitory effect of dipeptidyl
      peptidase-4 inhibitors on carotid IMT progression, in the PROLOGUE study
      sitagliptin failed to slow progression relative to conventional therapy for 24
      months. We hypothesized that differences in the concomitant antidiabetic agents
      between the groups have influenced the progression of carotid IMT. We performed a
      post hoc analysis of the PROLOGUE study using subgroups stratified by concomitant
      antidiabetic agents. Although no subgroup with any combination of agents in the
      overall patients showed a significant difference between sitagliptin group and
      conventional therapy group in the changes from baseline in mean common carotid
      artery (CCA)-IMT at 24 months, a significant attenuation of mean CCA-IMT
      progression was observed in the sitagliptin group relative to conventional
      therapy group only in three combination subgroups aged < 70 years, namely no
      thiazolidinedione; no thiazolidinedione or biguanide; and no thiazolidinedione,
      biguanide or alpha-glucosidase inhibitor, even after adjustment for multiple
      confounding factors. In the three subgroups, no significant difference between
      sitagliptin group and conventional therapy group in the changes from baseline in
      HbA1c at 24 months was detected. Our data suggest that some concomitant agents,
      whose prescription frequencies were increased in the conventional therapy group,
      may have masked the inhibitory effect of sitagliptin on carotid IMT progression
      in the PROLOGUE study.

PMID- 30284019
TI  - Oral ulceration: an unusual manifestation of lymphomatoid granulomatosis.

PMID- 30284020
TI  - A coil in the hair-a case report of percutaneous coil migration.
AB  - Coil migration following cerebral aneurysm treatment has been described and may
      result in stroke, recurrent aneurysm, or local mass effect. Cerebral coil
      embolization is also applied in arteriovenous malformations and arteriovenous
      fistulas, but these pathologies are relatively rare and coil migration is not as
      well described. Furthermore, these cases are more commonly treated with
      combinations of multiple modalities to achieve cure. Embolization, surgery, and
      radiation each have risks and benefits and combinations may have synergistic
      risks and benefits not seen in monotherapy. We report a case of extravascular and
      extra-corporeal coil migration after embolization and craniectomy to treat a
      patient with hemorrhage from an arteriovenous fistula.

PMID- 30284021
TI  - Redescription of Hedruris mucronifer (Nematoda: Hedruridae) parasite of
      Telmatobius schreiteri (Anura, Telmatobiidae) from Tucuman, Argentina.
AB  - The species Hedruris mucronifer Schuurmans Stekhoven, 1952 parasite of
      Telmatobius schreiteri from Tafi del Valle, Tucuman, Argentina is herein
      redescribed. The main morphological characters used for its identification are
      illustrated. The lectotype and paralectotype are designated, respectively. The
      specific epithet of the host is rectified.

PMID- 30284022
TI  - A novel liver retraction method in laparoscopic gastrectomy for gastric cancer.
AB  - BACKGROUND: Retracting the lateral liver segment during laparoscopic distal
      gastrectomy is important for achieving an optimal surgical field. However,
      excessive force may injure the liver, causing temporary abnormalities of liver
      function tests after laparoscopic surgery. We developed a new liver retraction
      method and assessed its safety and utility. PATIENTS AND METHODS: We
      retrospectively analyzed records in our surgical database of consecutive surgical
      patients who underwent laparoscopic distal gastrectomy for early gastric cancer.
      We divided the 229 patients into two groups based on the liver retraction method
      used, either flexible liver retraction with clipping and suturing (FLICS) or the
      Nathanson retractor (NR). One-to-one propensity score matching was performed to
      match patients, resulting in the records of 53 pairs of cases extracted from the
      database. Operative and postoperative outcomes were assessed, including following
      the values of serum liver enzymes, total bilirubin, and C-reactive protein until
      postoperative day 30. RESULTS: There were no significant differences in patient
      characteristics or preoperative data in the two groups. The retraction method was
      not changed intraoperatively for any patients. The operative time was
      significantly shorter in the FLICS group, but the amount of bleeding did not
      differ. Liver injury was not observed as a result of liver retraction during
      surgery. In both groups, serum liver enzymes temporarily increased after surgery
      but improved rapidly thereafter. The postoperative increases in aspartate
      transaminase, alanine transaminase, and C-reactive protein levels were
      significantly lower in the FLICS than in the NR group. No serious complications
      associated with liver retraction were observed in either group. CONCLUSIONS: Our
      new liver retraction technique provided an optimal surgical field without
      inducing liver dysfunction. It is a simple, safe, and effective liver retraction
      technique.

PMID- 30284024
TI  - Inherited cardiomyopathies in veterinary medicine.
AB  - Comparative and translation medicine is of particular value within the field of
      inherited cardiomyopathies. Despite massive advances in understanding the
      functional role of mutations in human cardiomyopathies, these advances have
      frequently failed to translate into medical discoveries that alter patient care.
      One potential explanation for this failure lies in the lack of suitable
      translational models that adequately recapitulate human cardiovascular physiology
      and disease expression. The vast genetic heterogeneity that complicates human
      cardiomyopathy research is potentially alleviated through the study of naturally
      occurring large animal models of disease, where incredibly homogenous
      populations, like those seen in a single breed of dog or cat, may exist (Kol et
      al., Sci Transl Med 7:308-321, 2015; Ueda and Stern, Yale J Biol Med 90:433-448,
      2017). Veterinary medicine is in a unique position to provide research resources
      and information that may be readily applied to human disease (Kol et al., Sci
      Transl Med 7:308-321, 2015). Many inherited cardiomyopathies of humans are
      phenotypically and genotypically similar in veterinary species and ongoing
      research holds promise for aiding veterinary and human patients alike (Basso et
      al., Circulation 109:1180-1185, 2004; Fox et al., Cardiovasc Pathol 23:28-34,
      2014; Fox et al., Circulation 102:1863-1870, 2000; Kittleson et al., J Vet
      Cardiol 17 Suppl 1:S53-73, 2015; Ueda and Stern, Yale J Biol Med 90:433-448,
      2017). This article presents the current knowledge of inherited cardiomyopathies
      in dogs, cats, and non-human primates, with a goal of identifying areas of
      translational research and future directions.

PMID- 30284023
TI  - Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a
      randomized controlled trial (JSKDC01 study).
AB  - BACKGROUND: Persistent proteinuria seems to be a risk factor for progression of
      renal disease. Its reduction by angiotensin-converting inhibitors (ACEIs) or
      angiotensin II receptor blockers (ARBs) is renoprotective. Our previous pilot
      study showed that 2-year lisinopril therapy is effective and safe for children
      with mild IgA nephropathy. When combined with ACEI and ARB, reported results are
      of greater decrease in proteinuria than monotherapy in chronic
      glomerulonephritis, including IgA nephropathy. To date, however, there have been
      no randomized controlled trials in children. METHODS: This is an open-label,
      multicenter, prospective, and randomized phase II controlled trial of 63 children
      with biopsy-proven proteinuric mild IgA nephropathy. We compared efficacy and
      safety between patients undergoing lisinopril monotherapy and patients undergoing
      combination therapy of lisinopril and losartan to determine better treatment for
      childhood proteinuric mild IgA nephropathy. RESULTS: There was no difference in
      proteinuria disappearance rate (primary endpoint) between the two groups
      (cumulative disappearance rate of proteinuria at 24 months: 89.3% vs 89%
      [combination vs monotherapy]). Moreover, there were no significant differences in
      side effects between the two groups. CONCLUSIONS: We propose lisinopril
      monotherapy as treatment for childhood proteinuric mild IgA nephropathy as there
      are no advantages of combination therapy. CLINICAL TRIAL REGISTRATION: Clinical
      trial registry, UMIN ID C000000006, https://www.umin.ac.jp .

PMID- 30284025
TI  - Objective and Subjective Sleep Efficiency in Adult Patients with Cystic Fibrosis
      and Impact on Quality of Life.
AB  - INTRODUCTION: Poor sleep quality and excessive daytime sleepiness are common in
      patients with cystic fibrosis (CF), and both are negatively correlated with
      health-related quality of life (HRQoL). The objective of our study was to
      evaluate subjective and objective sleep quality in adult CF patients and its
      effect on HRQoL. MATERIALS AND METHODS: This was a descriptive, prospective,
      cross-sectional study of CF patients > 18 years of age. Patients underwent
      nocturnal polysomnography (PSG) and were administered the Pittsburgh Sleep
      Quality Index questionnaire (PSQI) and the Cystic Fibrosis Quality of Life
      Questionnaire (CFQR 14 + Spain). RESULTS: The study included 23 patients, 14
      women (61%). The mean age of the participants was 32 + 18 years. The mean PSQI
      score was 5.57 + 3.55; 13 (56.5%) of the patients were poor sleepers, and 13%
      reported poor sleep quality; seven (30%) had sleep latency > 30 min, 10 (43.5%)
      had sleep efficiency < 85%. Nineteen underwent polysomnography. According to PSG
      measurements, sleep efficiency was less than 90% in 61% of the patients.
      Pathological values were found for the following parameters: intra-sleep
      wakefulness in 12 patients (63%); microarousal index in 12 patients (63%); and
      apnea-hypopnea index (AHI) in 2 patients. The desaturation time with SpO2 < 90%
      (T90) was > 30% in 3 patients. We observed a significant correlation between PSQI
      and all dimensions of CFQR 14. CONCLUSIONS: Subjective and objective sleep
      efficiency decreases in adult CF patients. Sleep quality has an impact on HRQoL.
      The PSQI questionnaire was able to discriminate sleep quality.

PMID- 30284026
TI  - Endothelial Function in COPD Is in an Intermediate Position Between Healthy
      Subjects and Coronary Artery Disease Patients and Is Related to Physical
      Activity.
AB  - Patients with chronic obstructive pulmonary disease (COPD) have an increased risk
      of ischemic heart disease. Endothelial dysfunction may play a role in the onset
      of cardiovascular event. Previous studies showed an impaired endothelial function
      (measured by flow-mediated dilation, FMD) in COPD patients compared to healthy
      subjects. To the best of our knowledge no study has compared FMD in COPD and in
      cardiac (coronary artery disease, CAD) patients. We aimed to assess FMD in
      healthy subjects, COPD, CAD, and COPD + CAD. The main result is that FMD in COPD
      is reduced and is in an intermediate position between healthy subjects and CAD or
      COPD + CAD; this impairment can contribute to explain the higher prevalence of
      cardiovascular disease in COPD. The only determinant independently associated
      with FMD in all subjects is the physical activity level, irrespective of the
      traditional risk factors (i.e., smoke, dyslipidemia, hypertension).

PMID- 30284027
TI  - Fluorometric determination of quercetin by using graphitic carbon nitride
      nanoparticles modified with a molecularly imprinted polymer.
AB  - The authors describe a fluorescent probe for sensitive and selective
      determination of quercetin, an indicator for the freshness of drinks. The probe
      consists of silica ball encapsulated graphitic carbon nitride (g-C3N4) modified
      with a molecularly imprinted polymer (MIP). It was synthesized via reverse
      microemulsion. The resulting MIP@g-C3N4 nanocomposite was characterized by
      fluorescence spectroscopy, transmission electron microscopy, Fourier transform
      infrared spectroscopy, and X-ray powder diffraction. Quercetin quenches the
      fluorescence of the MIP@g-C3N4 probe. The effect was used to quantify quercetin
      in grape juice, tea juice, black tea, and red wine by fluorometry (lambdaexc =
      350 nm, lambdaem = 460 nm). Response is linear in the 10-1000 ng mL-1 quercetin
      concentration range. The detection limit is 2.5 ng mL-1, recoveries range between
      90.7 and 94.1%, and relative standard deviations are between 2.1 and 5.5%.
      Graphical abstract Schematic of the synthesis of the MIP@g-C3N4 by a reverse
      microemulsion method. The probe was applied for the selective recognition and
      fluorometric determination of quercetin.

PMID- 30284028
TI  - Antagonist muscle architecture and aponeurosis/tendon strain of biceps femoris
      long head during maximal isometric efforts.
AB  - INTRODUCTION: Examination of the mechanical behavior of the hamstrings when
      acting as antagonists provides information about loading of this muscle group and
      its role for joint stability during forceful quadriceps contractions. The aim of
      this study was to quantify biceps femoris long head fascicle length (FL), angle
      of pennation (PA) and distal tendon/aponeurosis strain during maximum voluntary
      contraction efforts of the knee extensors using real-time ultrasound. METHODS:
      Fourteen participants performed passive joint movements and maximum voluntary
      knee extension and flexion efforts of the knee flexors at 0 degrees , 45 degrees 
      and 90 degrees  of knee flexion. An ultrasound probe was used to visualize FL, PA
      and tendon/aponeurosis strain from the distal part of the muscle. RESULTS: Two
      way analysis of variance designs indicated that: (a) antagonist BFlh
      tendon/aponeurosis strain increased significantly up to 2.77 +/- 1.25% relative
      to rest (p < 0.05). The FL increased non-significantly (2.86 +/- 6.81%) while the
      PA was unaltered during isometric MVC efforts of the knee extensors (p > 0.05)
      (b) FL, PA and tendon/aponeurosis strain of the BFlh when acting as antagonist
      were not significantly affected by knee joint angular position (p > 0.05).
      CONCLUSIONS: Antagonist hamstring function takes the form of a lengthened
      tendon/aponeurosis, no fascicle shortening and submaximal neural activation.
      Future research could examine whether exercise interventions that aim to alter
      tendon/aponeurosis mechanical properties of the hamstrings when acting as
      antagonists are beneficial for injury prevention and rehabilitation.

PMID- 30284029
TI  - Pain management in abdominal surgery.
AB  - BACKGROUND: Abdominal surgery has undergone major changes during the last two
      decades with a general shift from open, invasive surgery to closed minimally
      invasive surgery. Accordingly, pain management strategies have also changed,
      especially with the introduction of ultrasound-guided abdominal wall blocks.
      Despite laparoscopic abdominal surgery classified as minimal, pain can be quite
      significant and needs to be addressed appropriately. PURPOSE: This narrative
      review focuses on adequate pain strategies for various types of surgery. The
      respective techniques are described and examples of specific pain management
      strategies given. Advantages and disadvantages of techniques are discussed. This
      review can serve as a sort of empirical guideline and orientation for the reader
      to develop their own strategy as well as bringing surgeons up-to-date with the
      latest anesthetic techniques. CONCLUSION: Pain is not less or less relevant in
      minimally invasive surgery. New hallmarks of a multimodal pain strategy are
      abdominal wall blocks, either as single shot or continuously. Minor open surgery
      is best performed under a combination of loco-regional blocks and continuous
      sedation. Abdominal wall blocks, NSAIDs, and short-acting opioids given by nurses
      or as PCA present the best multimodal pain strategy in abdominal surgery.
      Epidural analgesia and spinal anesthesia have become second-line options or are
      reserved for specific patient morbidities or surgical requirements.

PMID- 30284030
TI  - Correction to: Tumour origin and R1 rates in pancreatic resections: towards
      consilience in pathology reporting.
AB  - The authors regret that one of the author's given name was missing and a
      typographical error was present in Reference 26 of the above article. These are
      presented correctly in this article.

PMID- 30284032
TI  - Abstracts for 32 GEER- Spanish Spine Society Congress in Avila, Spain, June 2018.

PMID- 30284031
TI  - An optoelectronic tongue based on an array of gold and silver nanoparticles for
      analysis of natural, synthetic and biological antioxidants.
AB  - A colorimetric array, which can discriminate 20 food antioxidants of natural,
      synthetic and biological groups, is described. It consists of gold and silver
      nanoparticles that were synthesized using six different reducing and/or capping
      agents. The function of the array relies on the interaction of the antioxidants
      with the nanoparticles which causes aggregation or morphological changes. This,
      in turn, causes a change in the sensors' colors. The array produces a unique
      combination of colors for each antioxidant. The resulting colorations are
      determined by recording the absorbances of the arrays at wavelengths of 405, 450,
      490 and 630 nm, or by capturing the images with a digital camera. The
      discriminatory ability of the array is investigated by principle component
      analysis and hierarchical cluster analysis. The method was applied to
      quantitative assay of gallic acid, caffeic acid, catechin, dopamine, citric acid,
      butylated hydroxytoluene and ascorbic acid. The respective limits of detection
      are 4.2, 13, 53, 6.9, 47, 3.5 and 43 nM, respectively. The simultaneous
      determination of 5 different antioxidants is achieved utilizing partial least
      square regression. The root mean square errors for prediction of the test set are
      0.0650, 0.0782, 0.811, 0.0206 and 0.135 nM for gallic acid, catechin, butylated
      hydroxytoluene, dopamine, and ascorbic acid, respectively. This method
      demonstrates excellent potential for analysis of antioxidants in beverages such
      as tea and lemon juice. Graphical abstract Schematic of a method for the
      simultaneous determination of several antioxidants based on changes in the color
      of gold and silver nanoparticles. The antioxidants cause aggregation and/or
      morphological changes which can be detected by using both image analysis or by
      colorimetry.

PMID- 30284033
TI  - Melanin-concentrating hormone neurons promote rapid eye movement sleep
      independent of glutamate release.
AB  - Neurons containing melanin-concentrating hormone (MCH) in the posterior lateral
      hypothalamus play an integral role in rapid eye movement sleep (REMs) regulation.
      As MCH neurons also contain a variety of other neuropeptides [e.g., cocaine- and
      amphetamine-regulated transcript (CART) and nesfatin-1] and neurotransmitters
      (e.g., glutamate), the specific neurotransmitter responsible for REMs regulation
      is not known. We hypothesized that glutamate, the primary fast-acting
      neurotransmitter in MCH neurons, is necessary for REMs regulation. To test this
      hypothesis, we deleted vesicular glutamate transporter (Vglut2; necessary for
      synaptic release of glutamate) specifically from MCH neurons by crossing MCH-Cre
      mice (expressing Cre recombinase in MCH neurons) with Vglut2flox/flox mice
      (expressing LoxP-modified alleles of Vglut2), and studied the amounts,
      architecture and diurnal variation of sleep-wake states during baseline
      conditions. We then activated the MCH neurons lacking glutamate neurotransmission
      using chemogenetic methods and tested whether these MCH neurons still promoted
      REMs. Our results indicate that glutamate in MCH neurons contributes to normal
      diurnal variability of REMs by regulating the levels of REMs during the dark
      period, but MCH neurons can promote REMs even in the absence of glutamate.

PMID- 30284034
TI  - Mutant superoxide dismutase aggregates from human spinal cord transmit
      amyotrophic lateral sclerosis.
AB  - Motor neurons containing aggregates of superoxide dismutase 1 (SOD1) are
      hallmarks of amyotrophic lateral sclerosis (ALS) caused by mutations in the gene
      encoding SOD1. We have previously reported that two strains of mutant human (h)
      SOD1 aggregates (denoted A and B) can arise in hSOD1-transgenic models for ALS
      and that inoculation of such aggregates into the lumbar spinal cord of mice
      results in rostrally spreading, templated hSOD1 aggregation and premature fatal
      ALS-like disease. Here, we explored whether mutant hSOD1 aggregates with prion
      like properties also exist in human ALS. Aggregate seeds were prepared from
      spinal cords from an ALS patient carrying the hSOD1G127Gfs*7 truncation mutation
      and from mice transgenic for the same mutation. To separate from mono-, di- or
      any oligomeric hSOD1 species, the seed preparation protocol included
      ultracentrifugation through a density cushion. The core structure of
      hSOD1G127Gfs*7 aggregates present in mice was strain A-like. Inoculation of the
      patient- or mouse-derived seeds into lumbar spinal cord of adult hSOD1-expressing
      mice induced strain A aggregation propagating along the neuraxis and premature
      fatal ALS-like disease (p < 0.0001). Inoculation of human or murine control seeds
      had no effect. The potencies of the ALS patient-derived seed preparations were
      high and disease was initiated in the transgenic mice by levels of hSOD1G127Gfs*7
      aggregates much lower than those found in the motor system of patients carrying
      the mutation. The results suggest that prion-like growth and spread of hSOD1
      aggregation could be the primary pathogenic mechanism, not only in hSOD1
      transgenic rodent models, but also in human ALS.

PMID- 30284035
TI  - Rebuttal to Drs. Grinberg and Heinsen.

PMID- 30284036
TI  - Alginate immobilization of Morus alba L. cell suspension cultures improved the
      accumulation and secretion of stilbenoids.
AB  - Morus alba L. (Moraceae) has been used in traditional medicine for the treatment
      of several illnesses. Recent research also revealed several pharmacological
      activities from many groups of secondary metabolites, including the stilbenoids
      mulberroside A, oxyresveratrol, and resveratrol, which are promising compounds
      for cosmetic and herbal supplement products. In our previous study, cell cultures
      of M. alba showed high productivity of these compounds. In this study, we
      attempted to develop immobilized cell cultures of M. alba and to test the effect
      of elicitors and precursors on the production of stilbenoids. The immobilization
      of the M. alba cells significantly promoted the secretion of mulberroside A into
      the extracellular matrix and culture media to 60%, while enhancing the level of
      oxyresveratrol and resveratrol by 12- and 27-fold, respectively. The elicitation
      of immobilized cells with a combination of 50 uM methyl jasmonate and 0.5 mg/mL
      yeast extract for 24 h promoted a twofold increase in the production of all three
      stilbenoids. Furthermore, the addition of 0.05 mM L-phenylalanine, 0.03 mM L
      tyrosine, or a combination resulted in the enhancement of mulberroside A
      production for up to twofold. The addition of L-tyrosine significantly enhanced
      the production of oxyresveratrol and resveratrol. This is the first report of
      stilbenoid production using immobilized cell cultures of M. alba. The cultures
      have benefits over normal cell suspension cultures by promoting the secretion of
      mulberroside A and enhancing the levels of oxyresveratrol and resveratrol. Thus,
      it could be a candidate method for the production of these stilbenoids.

PMID- 30284037
TI  - Spinocerebellar ataxia: an update.
AB  - Spinocerebellar ataxia (SCA) is a heterogeneous group of neurodegenerative ataxic
      disorders with autosomal dominant inheritance. We aim to provide an update on the
      recent clinical and scientific progresses in SCA where numerous novel genes have
      been identified with next-generation sequencing techniques. The main disease
      mechanisms of these SCAs include toxic RNA gain-of-function, mitochondrial
      dysfunction, channelopathies, autophagy and transcription dysregulation. Recent
      studies have also demonstrated the importance of DNA repair pathways in modifying
      SCA with CAG expansions. In addition, we summarise the latest technological
      advances in detecting known and novel repeat expansion in SCA. Finally, we
      discuss the roles of antisense oligonucleotides and RNA-based therapy as
      potential treatments.

PMID- 30284038
TI  - Vitamin D for the treatment of multiple sclerosis: a meta-analysis.
AB  - OBJECTIVE: There is an association between latitude, relative vitamin D
      deficiency and risk of multiple sclerosis (MS), and an association between
      vitamin D and disease progression. We have performed a meta-analysis with the aim
      of investigating the role of therapeutic vitamin D in MS. METHODS: A systematic
      search of databases was performed to identify clinical trials assessing vitamin D
      in patients with relapsing-remitting MS. Studies were selected based on inclusion
      and exclusion criteria. Analysis was performed using RevMan 5.3 software.
      RESULTS: Twelve studies involving 950 patients were included in the final
      analysis. Studies were divided into four groups because of heterogeneity in study
      design. Studies were judged to be at low or unclear risk of bias, except in three
      studies, and this was confirmed by funnel plots. No statistically significant
      difference was seen for any of the outcome measures. There were non-significant
      trends in favour of vitamin D for all outcome measures, particularly when only
      placebo-controlled studies were included. Dose comparison studies showed a
      significant increase in annualised relapse rate (mean difference 0.15 [95%CI 0.01
      0.30]) and non-significant trends of increased Expanded Disability Status Scale
      and gadolinium-enhancing lesions for the higher-dose arms. CONCLUSION: These
      findings suggest that vitamin D supplementation may have a therapeutic role in
      the treatment of MS. However, there is uncertainty with regard to the most
      appropriate dose, with high doses potentially being associated with worse
      outcomes. There remains the need for further well-performed randomised, dose
      ranging, placebo-controlled trials of vitamin D in MS.

PMID- 30284039
TI  - ASCO, NCCN, MASCC/ESMO: a comparison of antiemetic guidelines for the treatment
      of chemotherapy-induced nausea and vomiting in adult patients.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is a common toxicity that may
      impair the quality of life of patients with a variety of early- and end-stage
      malignancies. In light of recent changes in the optimal management of CINV, we
      undertook this narrative review to compare the latest guidelines published by
      ASCO (2017), NCCN (2018), and MASCC/ESMO (2016). The processes undertaken by each
      organization to evaluate existing literature were also described. Although ASCO,
      NCCN, and MASCC/ESMO guidelines for the treatment and prevention of CINV share
      many fundamental similarities, literature surrounding low and minimal emetic risk
      regimens is lacking. Data regarding the use of complementary alternative medicine
      for CINV is particularly scarce and in need of further investigation.

PMID- 30284040
TI  - Design, implementation, and evaluation of an intervention to improve referral to
      smoking cessation services in breast cancer patients.
AB  - PURPOSE: Smoking is a risk factor for poor outcomes following breast
      reconstructive surgery. This project aimed to design and implement an
      intervention to consistently refer all breast cancer patients to tobacco
      treatment services. METHODS: In formative work, a set of processes for providers
      to consistently refer patients to a tobacco treatment specialist at the Nicotine
      Dependence Center (NDC) was designed. Elements included consistent documentation
      of smoking status, provider advice specific to the benefits of quitting to cancer
      care, referral to NDC using an "opt-out" strategy that emphasized smoking
      cessation as a standard part of breast cancer treatment, and reinforcement of the
      importance of the referral by multiple personnel. The number of referrals to the
      NDC and number of patients who attended their scheduled NDC appointment were
      measured before and 1 year after implementation. Qualitative evaluation was
      performed using semi-structured interviews with participating providers and
      patients regarding acceptability. RESULTS: The proportion of smoking patients
      referred to the NDC increased from 29% (22/75) before the intervention to 74%
      (20/27) afterward. Among those referred, attendance at the consultation increased
      from 41% (9/22) to 75% (15/20). This occurred despite provider interviews
      revealing knowledge gaps about the referral process and evidence of provider
      adaptation to accommodate personal practice. Feasibility and acceptability of the
      intervention were high. CONCLUSION: These findings suggest that similar referral
      interventions for all cancer patients should be pursued with the aim of embedding
      tobacco dependence treatment seamlessly and consistently into the cancer
      treatment plan of every patient who smokes cigarettes.

PMID- 30284041
TI  - Validation of dynamic random dot stereotests in pediatric vision screening.
AB  - PURPOSE: Stereo vision tests are widely used in the clinical practice for
      screening amblyopia and amblyogenic conditions. According to literature, none of
      these tests seems to be suitable to be used alone as a simple and reliable tool.
      There has been a growing interest in developing new types of stereo vision tests,
      with sufficient sensitivity to detect amblyopia. This new generation of
      assessment tools should be computer based, and their reliability must be
      statistically warranted. The present study reports the clinical evaluation of a
      screening system based on random dot stereograms using a tablet as display.
      Specifically, a dynamic random dot stereotest with binocularly detectable Snellen
      E optotype (DRDSE) was used and compared with the Lang II stereotest. METHODS: A
      total of 141 children (aged 4-14, mean age 8.9) were examined in a field study at
      the Department of Ophthalmology, Pecs, Hungary. Inclusion criteria consisted of
      diagnoses of amblyopia, anisometropia, convergent strabismus, and hyperopia.
      Children with no ophthalmic pathologies were also enrolled as controls. All
      subjects went through a regular pediatric ophthalmological examination before
      proceeding to the DRDSE and Lang II tests. RESULTS: DRDSE and Lang II tests were
      compared in terms of sensitivity and specificity for different conditions. DRDSE
      had a 100% sensitivity both for amblyopia (n = 11) and convergent strabismus (n =
      21), as well as a 75% sensitivity for hyperopia (n = 36). However, the
      performance of DRDSE was not statistically significant when screening for
      anisometropia. On the other hand, Lang II proved to have 81.8% sensitivity for
      amblyopia, 80.9% for strabismus, and only 52.8% for hyperopia. The specificity of
      DRDSE was 61.2% for amblyopia, 67.3% for strabismus, and 68.6% for hyperopia,
      respectively. Conversely, Lang II showed about 10% better specificity, 73.8% for
      amblyopia, 79.2% for strabismus, and 77.9% for hyperopia. CONCLUSIONS: The DRDSE
      test has a better sensitivity for the detection of conditions such as amblyopia
      or convergent strabismus compared with Lang II, although with slightly lower
      specificity. If the specificity could be further improved by optimization of the
      stimulus parameters, while keeping the sensitivity high, DRDSE would be a
      promising stereo vision test for screening of amblyopia.

PMID- 30284042
TI  - Tracking Nosocomial Diseases at Individual Level with a Real-Time Indoor
      Positioning System.
AB  - Our research is motivated by the rapidly-evolving outbreaks of rare and fatal
      infectious diseases, for example, the severe acute respiratory syndrome (SARS)
      and the Middle East respiratory syndrome. In many of these outbreaks, main
      transmission routes were healthcare facility-associated and through person-to
      person contact. While a majority of existing work on modelling of the spread of
      infectious diseases focuses on transmission processes at a community level, we
      propose a new methodology to model the outbreaks of healthcare-associated
      infections (HAIs), which must be considered at an individual level. Our work also
      contributes to a novel aspect of integrating real-time positioning technologies
      into the tracking and modelling framework for effective HAI outbreak control and
      prompt responses. Our proposed solution methodology is developed based on three
      key components - time-varying contact network construction, individual-level
      transmission tracking and HAI parameter estimation - and aims to identify the
      hidden health state of each patient and worker within the healthcare facility. We
      conduct experiments with a four-month human tracking data set collected in a
      hospital, which bore a big nosocomial outbreak of the 2003 SARS in Hong Kong. The
      evaluation results demonstrate that our framework outperforms existing epidemic
      models for characterizing macro-level phenomena such as the number of infected
      people and epidemic threshold.

PMID- 30284043
TI  - SERS based aptasensor for ochratoxin A by combining Fe3O4@Au magnetic
      nanoparticles and Au-DTNB@Ag nanoprobes with multiple signal enhancement.
AB  - A SERS-based aptasensor for ochratoxin A (OTA) is described. It is making use of
      Fe3O4@Au magnetic nanoparticles (MGNPs) and of Au@Ag nanoprobes modified with the
      Raman reporter 5,5-dithiobis-(2-nitrobenzoic acid; DTNB). Au-DTNB@Ag NPs were
      modified with the OTA aptamer (aptamer-GSNPs) and used as Raman signal probes.
      The SERS peak of DTNB at 1331 cm-1 was used for quantitative analysis. MGNPs
      modified with cDNA (cDNA-MGNPs) were used as capture probes and reinforced
      substrates. When the Au-DTNB@Ag-Fe3O4@Au complexes are formed through
      oligonucleotide hybridization, the Raman signal intensity of the Raman probe is
      significantly enhanced. If the OTA concentration in samples increases, more Raman
      signal probes (aptamer-GSNPs) will dissociate from the cDNA-MGNPs because more
      OTA aptamer is bound by OTA. This leads to a lower Raman signal after magnetic
      separation. Under the optimal conditions, the detection limit for OTA is 0.48
      pg.mL-1 based on 3sigma criterion. This is attributed to the multiple Raman
      signal enhancement and the good performance of the OTA aptamer. The good recovery
      and accuracy of the assay was confirmed by evaluating spiked samples of wine and
      coffee. Graphical abstract Schematic of an aptamer based SERS assay for OTA by
      integrating Fe3O4@AuNPs (MGNPs) with Au-DTNB@Ag NPs with multiple signal
      enhancement. Aptamer modified Au-DTNB@Ag NPs are used as Raman probes, and MGNPs
      modified with cDNA are used as capture probes and reinforced substrates.

PMID- 30284045
TI  - CRISPR RNA-guided DNA cleavage by reconstituted Type I-A immune effector
      complexes.
AB  - Diverse CRISPR-Cas immune systems protect archaea and bacteria from viruses and
      other mobile genetic elements. All CRISPR-Cas systems ultimately function by
      sequence-specific destruction of invading complementary nucleic acids. However,
      each CRISPR system uses compositionally distinct crRNP [CRISPR (cr) RNA/Cas
      protein] immune effector complexes to recognize and destroy invasive nucleic
      acids by unique molecular mechanisms. Previously, we found that Type I-A (Csa)
      effector crRNPs from Pyrococcus furiosus function in vivo to eliminate invader
      DNA. Here, we reconstituted functional Type I-A effector crRNPs in vitro with
      recombinant Csa proteins and synthetic crRNA and characterized properties of
      crRNP assembly, target DNA recognition and cleavage. Six proteins (Csa 4-1,
      Cas3", Cas3', Cas5a, Csa2, Csa5) are essential for selective target DNA binding
      and cleavage. Native gel shift analysis and UV-induced RNA-protein crosslinking
      demonstrate that Cas5a and Csa2 directly interact with crRNA 5' tag and guide
      sequences, respectively. Mutational analysis revealed that Cas3" is the effector
      nuclease of the complex. Together, our results indicate that DNA cleavage by Type
      I-A crRNPs requires crRNA-guided and protospacer adjacent motif-dependent target
      DNA binding to unwind double-stranded DNA and expose single strands for
      progressive ATP-dependent 3'-5' cleavage catalyzed by integral Cas3' helicase and
      Cas3" nuclease crRNP components.

PMID- 30284044
TI  - Correction to: A pregnancy test strip for detection of pathogenic bacteria by
      using concanavalin A-human chorionic gonadotropin-Cu3(PO4)2 hybrid nanoflowers,
      magnetic separation, and smartphone readout.
AB  - The published version of this article, unfortunately, contained error. The
      authors are re-writing to express their sincere apology for a mistake that a mark
      "10-5, 10-4, 10-3, 10-2, 10-1 CFU*mL-1" in the legend of Fig. 2 was not corrected
      as "105, 104, 103, 102, 101 CFU*mL-1".

PMID- 30284046
TI  - Detection of gastritis by a deep convolutional neural network from double
      contrast upper gastrointestinal barium X-ray radiography.
AB  - BACKGROUND: Deep learning has become a new trend of image recognition tasks in
      the field of medicine. We developed an automated gastritis detection system using
      double-contrast upper gastrointestinal barium X-ray radiography. METHODS: A total
      of 6520 gastric X-ray images obtained from 815 subjects were analyzed. We
      designed a deep convolutional neural network (DCNN)-based gastritis detection
      scheme and evaluated the effectiveness of our method. The detection performance
      of our method was compared with that of ABC (D) stratification. RESULTS:
      Sensitivity, specificity, and harmonic mean of sensitivity and specificity of our
      method were 0.962, 0.983, and 0.972, respectively, and those of ABC (D)
      stratification were 0.925, 0.998, and 0.960, respectively. Although there were 18
      false negative cases in ABC (D) stratification, 14 of those 18 cases were
      correctly classified into the positive group by our method. CONCLUSIONS: Deep
      learning techniques may be effective for evaluation of gastritis/non-gastritis.
      Collaborative use of DCNN-based gastritis detection systems and ABC (D)
      stratification will provide more reliable gastric cancer risk information.

PMID- 30284047
TI  - Malnutrition in type 2 diabetic patients does not affect healing of foot ulcers.
AB  - AIM: Protein-energy malnutrition is known to be involved in wound healing. While
      wound healing in patients with diabetic foot ulcers (DFU) is a complex and
      multifactorial process, the role of malnutrition in this case has rarely been
      explored. The objective of this study was to determine whether the nutritional
      status of diabetic patients influences the healing of DFU. METHODS: 48 patients
      were included in this prospective, single-center study. All patients with
      comorbidities or factors involving malnutrition or influencing biological
      measurements were excluded. Patients were followed up for 24 weeks. RESULTS: The
      malnutrition rate was 29.2% at baseline and 25.6% at the end of the study. The
      difference was not significant. Of the 35 patients with wound healing, 29% were
      undernourished at inclusion and 17% at the end of the study. Of the 12 patients
      without wound healing, 50% were undernourished at inclusion, and 42% at the end
      of the study. These differences were not significant. Rate and speed of wound
      healing were not associated with malnutrition at inclusion. 15% of patients
      without malnutrition at baseline had final malnutrition. CONCLUSION: We
      demonstrated that wound healing was not affected by the initial presence of
      malnutrition. In our study, there is no evidence to support nutritional
      intervention to improve wound healing in diabetic patients. Nevertheless,
      malnutrition is responsible for an increase in morbidity and mortality and it is
      essential to identify malnutrition systematically for all patients with DFU,
      initially and during follow-up to treat it quickly and efficiently.

PMID- 30284048
TI  - In Situ Electrospinning Iodine-Based Fibrous Meshes for Antibacterial Wound
      Dressing.
AB  - For effective application of electrospinning and electrospun fibrous meshes in
      wound dressing, we have in situ electrospun poly(vinyl pyrrolidone)/iodine
      (PVP/I), PVP/poly(vinyl pyrrolidone)-iodine (PVPI) complex, and poly(vinyl
      butyral) (PVB)/PVPI solutions into fibrous membranes by a handheld
      electrospinning apparatus. The morphologies of the electrospun fibers were
      examined by SEM, and the hydrophobicity, gas permeability, and antibacterial
      properties of the as-spun meshes were also investigated. The flexibility and
      feasibility of in situ electrospinning PVP/I, PVP/PVPI, and PVB/PVPI membranes,
      as well as the excellent gas permeabilities and antibacterial properties of the
      as-spun meshes, promised their potential applications in wound healing.

PMID- 30284050
TI  - Photovoltaic Performance of Pin Junction Nanocone Array Solar Cells with Enhanced
      Effective Optical Absorption.
AB  - The photovoltaic performance of axial and radial pin junction GaAs nanocone array
      solar cells is investigated. Compared with the cylinder nanowire arrays, the
      nanocone arrays not only improve the whole optical absorption but more
      importantly enhance the effective absorption (absorption in the depletion
      region). The enhanced effective absorption is attributed to the downward shift
      and extension of the absorption region induced by the shrinking top, which
      dramatically suppresses the absorption loss in the high-doped top region and
      enhances the absorption in the depletion region. The highest conversion
      efficiencies for axial and radial GaAs nanocone solar cells are 20.1% and 17.4%,
      obtained at a slope angle of 5 degrees  and 6 degrees , respectively, both of
      which are much higher than their cylinder nanowire counterparts. The nanocone
      structures are promising candidates for high-efficiency solar cells.

PMID- 30284049
TI  - Biomarkers in Food Allergy.
AB  - PURPOSE OF REVIEW: To familiarize the reader with the concept of precision
      medicine in food allergy by dealing with the current biomarkers for the
      diagnosis, prognosis, and management of the disease. RECENT FINDINGS: Many
      efforts have been devoted in order to characterize reliable biomarkers able to
      identify specific phenotypes and endotypes in food allergy. Specific IgE (sIgE),
      sIgE/total IgE ratios, and T cell assays are just a few candidates that have been
      investigated over time. With the advent of omics sciences, a new era is
      commencing. A better understanding of pathogenesis of food allergy and mechanisms
      of action of the different therapeutic options will allow the accurate selection
      of the appropriate patient. In the near future, advances in technologies and data
      interpretation will allow a better understanding of the pathogenesis of food
      allergy and the identification of proper biomarkers for a personalized treatment
      tailored on the specific patient's profile.

PMID- 30284051
TI  - Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and
      Meta-Analysis of Clinical Trials.
AB  - PURPOSE OF REVIEW: Several interventional studies assessed the impact of dietary
      supplements on blood pressure. The aim of the present systematic review and meta
      analysis was to determine the efficacy of L-citrulline supplementation on blood
      pressure. RECENT FINDING: Pubmed, Scopus, Google Scholar, and ISI Web of Science
      were comprehensively searched until May 2018 to assess whether L-citrulline
      reduces blood pressure. Human clinical trials which reported the effect of L
      citrulline supplementation on aortic and brachial blood pressure were included.
      Characteristics of studies and potential sources of heterogeneity were tabulated.
      A subgroup analysis was performed to attenuate observed inter-study
      heterogeneity. A total of five interventions were found for meta-analysis. The
      impact of L-citrulline on brachial systolic (change 0.28 mmHg; 95% CI - 2.87,
      2.31 mmHg) and diastolic (change - 1.56 mmHg; 95% CI - 4.32, 1.20 mmHg) blood
      pressure was not significant. Also, there was no changes in aortic systolic
      (change 0.22 mmHg; 95% CI - 4.81, 4.38 mmHg) and diastolic (change 0.26 mmHg; 95%
      CI - 2.27, 2.80 mmHg) blood pressure after L-citrulline supplementation.
      Participants' body weight status was a source of observed heterogeneity. The
      present systematic review and meta-analysis suggests that L-citrulline
      supplementation had no beneficial effect on blood pressure.

PMID- 30284052
TI  - Multilayered Deep Structure Tensor Delaunay Triangulation and Morphing Based
      Automated Diagnosis and 3D Presentation of Human Macula.
AB  - Maculopathy is the group of diseases that affects central vision of a person and
      they are often associated with diabetes. Many researchers reported automated
      diagnosis of maculopathy from optical coherence tomography (OCT) images. However,
      to the best of our knowledge there is no literature that presents a complete 3D
      suite for the extraction as well as diagnosis of macula. Therefore, this paper
      presents a multilayered convolutional neural networks (CNN) structure tensor
      Delaunay triangulation and morphing based fully autonomous system that extracts
      up to nine retinal and choroidal layers along with the macular fluids.
      Furthermore, the proposed system utilizes the extracted retinal information for
      the automated diagnosis of maculopathy as well as for the robust reconstruction
      of 3D macula of retina. The proposed system has been validated on 41,921 retinal
      OCT scans acquired from different OCT machines and it significantly outperformed
      existing state of the art solutions by achieving the mean accuracy of 95.27% for
      extracting retinal and choroidal layers, mean dice coefficient of 0.90 for
      extracting fluid pathology and the overall accuracy of 96.07% for maculopathy
      diagnosis. To the best of our knowledge, the proposed framework is first of its
      kind that provides a fully automated and complete 3D integrated solution for the
      extraction of candidate macula along with its fully automated diagnosis against
      different macular syndromes.

PMID- 30284055
TI  - Correction to: Modeling interactions between saturated and un-saturated zones by
      Hydrus-1D in semi-arid regions (plain of Kairouan, Central Tunisia).
AB  - The Fig. 3 in this article has been obscured as the required permissions to
      reproduce it were not obtained.

PMID- 30284053
TI  - Metagenome sequencing to analyze the impacts of thiamine supplementation on
      ruminal fungi in dairy cows fed high-concentrate diets.
AB  - Ruminal thiamine deficiencies occur when dairy cows are overfed with high
      concentrate diet, and thiamine supplementation has been proved to attenuate high
      concentrate diet induced SARA. However, there is limited knowledge of the
      relationship between thiamine supplementation in high-concentrate diets and
      ruminal fungi. In order to investigate the impacts of thiamine supplementation on
      ruminal fungi, twelve Chinese Holstein dairy cows were randomly assigned into
      three treatments: control diet (CON; 20% starch, dry matter basis), high
      concentrate diet (HC; 33.2% starch, dry matter basis) and high-concentrate diet
      supplemented with 180 mg thiamine/kg dry matter intake. Dry matter intake and
      milk production were recorded during the experimental periods. On day 21, rumen
      fluid samples were collected at 3 h postfeeding and ruminal pH, thiamine
      concentration and volatile fatty acids were measured. Metagenome sequencing
      method was conducted to detect ruminal fungi composition. Feeding HC
      significantly decreased dry matter intake, milk production, ruminal pH, ruminal
      acetate and thiamine concentration, however, significantly increased propionate
      and isovalerate (P < 0.05). These changes were inversed by thiamine
      supplementation (P < 0.05). Totally, seven phyla and almost 1050 species of rumen
      fungi were identified across all samples in which especially, 3 genera and 10
      species of strictly anaerobic fungi phylum Neocallimastigomycota was found.
      Principal coordinate analysis indicated that feeding HC and thiamine
      supplementation caused a significant inverse in ruminal fungi composition.
      Feeding HC significantly decreased the abundance of fungi compared with CON (P <
      0.05) while thiamine supplementation significantly increased the abundance of
      ruminal fungi (P < 0.05). These results indicated that thiamine supplementation
      may effectively attenuate rumen metabolic disorder caused by HC diet through
      buffering the ruminal pH, shifting the rumen fermentation pattern and increasing
      the abundance of ruminal fungi. The findings in this study could therefore
      contribute to the further understanding of the mechanism of thiamine's function
      in dairy cows.

PMID- 30284056
TI  - Hirayama disease: analysis of cases in Russia.
AB  - The fourteen cases of Hirayama disease (HD) are presented in this article. HD is
      seldom disease characterized by juvenile muscular atrophy of upper extremities
      and benign course. All cases were diagnosed in the Research Center of Neurology
      (Moscow, Russia) during the year 2015-2017. Such methods as MRI (magnetic
      resonance imaging), EMG (electromyography), and NCS (nerve conduction studies)
      have been used to confirm diagnosis of HD. Transcranial magnetic stimulation was
      used to exclude upper motor neuron involvement in two cases. The original scale
      of neurological disturbances in HD has been proposed by authors to reveal
      correlations of HD severity with age of patients and duration of disease.Most of
      patients with HD are young males with common clinical signs. Detected MRI and EMG
      data were also comparable with previous publications. Independence of HD severity
      from age and duration of the disease may be the result of individual physical
      characteristics of dura mater and other structures of the cervical vertebra. In
      some our cases, amyotrophic lateral sclerosis and other neurological disorders
      were misdiagnosed before. In view of different prognosis in these pathologies and
      possible correction of HD, early diagnosis is very important.

PMID- 30284054
TI  - Plant specific emission pattern of biogenic volatile organic compounds (BVOCs)
      from common plant species of Central India.
AB  - In this study, we examined 49 representative plant species of the Achanakmar
      Amarkantak Biosphere Reserve (AABR) forest of Central India for emission of a
      number of biogenic volatile organic compounds (BVOCs). The BVOCs emissions from
      seven plant species are reported here for the first time. The emission rates of
      different plant species were ranged from negligible to 80.6 +/- 0.82 (MUgg-1 h
      1). Forty-seven plant species were found to emit isoprene and monoterpenes (23
      high emitters, 12 moderate emitters, and 12 low emitters). Dalbergia sissoo
      showed the maximum total average volatile organic compound (TAVOC) emission rates
      (80.6 MUgg-1 h-1). The percentage composition of monoterpenes was also varied
      across different plant species. Alpha-pinene (alpha-pinene) was found as the most
      dominant monoterpene with about 41.40% of the total monoterpene emission. The
      highest emission range of alpha-pinene (7.8 MUg g-1 h-1) was observed in Murraya
      koenigii. Carene was emitted only from two species (i.e., Mangifera indica and
      Terminalia tomentosa). When the emission rates of present study were compared to
      previous studies, there were considerable differences even for the same species.
      The study also reports the emission of BVOCs from Shorea robusta for the first
      time which is the most dominant plant species of the AABR (covering 60% of the
      total forest area).

PMID- 30284057
TI  - On the electron flow sequence driving the hydrometallation of acetylene by
      lithium hydride.
AB  - The sequence of the electronic flow driving the hydrometallation of acetylene by
      lithium hydride (and that of the opposite beta-hydride elimination reaction from
      the alkenyl metal intermediate), was examined within the perspective provided by
      the bonding evolution theory (BET). The analysis was based on the application of
      catastrophe theory to the changes of the electron localization function topology
      along the intrinsic reaction coordinate. The description of the electronic
      processes occurring on the process was represented in terms of topological
      structural stability domains (SSDs) and the associated elementary bifurcation
      catastrophes. Within such a framework of representation, the "evolution" of the
      system through the different SSDs reveals the key chemical events driving the
      transformation, including the large polarization effect as a consequence of Pauli
      repulsion between ions of the positive cationic metal on the hydride domain, the
      activation of the CC triple bond to attack the cationic center, and the agostic
      stabilizing interactions involving the hardest cationic metal, followed by the
      attack of the hydride center. These results contribute to emphasizing the
      intrinsic value and usefulness of using topological-based approaches and
      associated tools to increase our knowledge and understanding of the subtleties
      underlying the electronic flow as nuclei evolve along the reaction coordinate,
      providing detailed and complementary insights in comparison to other
      interpretative tool such those based on orbital-based representations, concerning
      the intimate nature of the electronic rearrangement of key mechanistic processes
      in chemistry. Graphical abstract The sequence of the electron flow (indicated by
      letters a and b) along the intrinsic reaction path for the hydrometallation of
      acetylene by lithium hydride to yield ethenyl lithium via a four-membered
      transition structure (TS), as determined within the bonding evolution theory to
      provide the key chemical events driven the changes in the key bonding patterns.
      Blue arrow Main event on the side HC = CH + LiH -> TS, red arrow the TS ->
      HLiC=CH2 pathway, green arrows relative motion of nuclei along the imaginary
      frequency at the position of TS on the intrinsic reaction coordinate.

PMID- 30284058
TI  - The study to environmental factors using microclimate survey of traditional
      wooden Silsang Temple in Korea.
AB  - Weathering of wooden temples is attributable to temperature and humidity. Here,
      we explore the microclimatic characteristics of a traditional Korean temple; we
      measured temperature, relative humidity, wind velocity, and wind direction at one
      internal and five external points in/near Silsang Temple. Both the temperature
      and humidity varied by season. The internal and external daily temperature ranges
      were most similar in autumn, followed by spring, winter, and summer. The relative
      humidity inside was 40% greater (compared to outside) in spring and winter, but
      not in summer and autumn. Wind velocity variations within the temple were
      significant in certain seasons. Neither the outside temperature nor internal
      relative humidity was greatly affected by location. Correlations were evident
      between the outside temperature and relative humidity.

PMID- 30284059
TI  - Hemodynamic assessment of pulmonary hypertension in mice: a model-based analysis
      of the disease mechanism.
AB  - This study uses a one-dimensional fluid dynamics arterial network model to infer
      changes in hemodynamic quantities associated with pulmonary hypertension in mice.
      Data for this study include blood flow and pressure measurements from the main
      pulmonary artery for 7 control mice with normal pulmonary function and 5 mice
      with hypoxia-induced pulmonary hypertension. Arterial dimensions for a 21-vessel
      network are extracted from micro-CT images of lungs from a representative control
      and hypertensive mouse. Each vessel is represented by its length and radius.
      Fluid dynamic computations are done assuming that the flow is Newtonian, viscous,
      laminar, and has no swirl. The system of equations is closed by a constitutive
      equation relating pressure and area, using a linear model derived from stress
      strain deformation in the circumferential direction assuming that the arterial
      walls are thin, and also an empirical nonlinear model. For each dataset, an
      inflow waveform is extracted from the data, and nominal parameters specifying the
      outflow boundary conditions are computed from mean values and characteristic
      timescales extracted from the data. The model is calibrated for each mouse by
      estimating parameters that minimize the least squares error between measured and
      computed waveforms. Optimized parameters are compared across the control and the
      hypertensive groups to characterize vascular remodeling with disease. Results
      show that pulmonary hypertension is associated with stiffer and less compliant
      proximal and distal vasculature with augmented wave reflections, and that elastic
      nonlinearities are insignificant in the hypertensive animal.

PMID- 30284061
TI  - Behavior Genetics Association 48th Annual Meeting Abstracts.

PMID- 30284060
TI  - Response of microbial community structure and metabolic profile to shifts of
      inlet VOCs in a gas-phase biofilter.
AB  - The effects of inlet VOCs (Volatile Organic Compounds) shifts on microbial
      community structure in a biofiltration system were investigated. A lab-scale
      biofilter was set up to treat eight VOCs sequentially. Short declines in removal
      efficiency appeared after VOCs shifts and then later recovered. The number of
      OTUs in the biofilter declined from 690 to 312 over time. At the phylum level,
      Actinobacteria and Proteobacteria remained dominant throughout the operation for
      all VOCs, with their combined abundance ranging from 60 to 90%. The abundances of
      Planctomycetes and Thermi increased significantly to 20% and 5%, respectively,
      with the intake of non-aromatic hydrocarbons. At the genus level, Rhodococcus was
      present in the highest abundance (>= 10%) throughout the experiment, indicating
      its wide degradability. Some potential degraders were also found; namely, Thauera
      and Pseudomonas, which increased in abundance to 19% and 12% during treatment
      with ethyl acetate and toluene, respectively. Moreover, the microbial metabolic
      activity declined gradually with time, and the metabolic profile of the toluene
      treating community differed significantly from those of other communities.

PMID- 30284062
TI  - A semi-dominant mutation in a CC-NB-LRR-type protein leads to a short-root
      phenotype in rice.
AB  - The mechanisms of plant defense against pathogen attack in plant leaves have been
      extensively studied. However, our understanding of plant defense mechanisms in
      plant roots is still limited. In this study, a semi-dominant mutant nrtp1-D
      (necrotic root tip 1), with a short-root phenotype, was characterized in rice.
      Map-based cloning revealed that NRTP1 encoded a typical coiled-coil nucleotide
      binding leucine rich repeat (CC-NB-LRR) type protein and the mutation caused an
      amino acid substitution in the Nucleotide-Binding adaptor shared by Apaf1,
      certain R genes and CED4 (NB-ARC) domain, which may cause constitutive auto
      activation of the NRTP1 protein. Gene expression analysis revealed that NRTP1 was
      preferentially expressed in rice roots. Expression of mutant nrtp1-D in tobacco
      leaves induced necrotic lesions, which indicated a common mechanism of plant
      defense response between leaves and roots. Transcriptome analysis revealed that
      many typical defense-response genes were differentially expressed in homozygous
      nrtp1-D. In addition, we also found differential expression of genes in pathways
      which had not previously been described as being associated with pathogen
      response. Histochemical analysis showed that the level of nitric oxide (NO), but
      not reactive oxygen species (ROS), was increased in homozygous nrtp1-D mutant
      roots. These results indicate that, in addition to the mechanism of defense
      response common to both roots and shoots, a novel pathway may also exist in rice
      roots, which does not operate in shoots.

PMID- 30284063
TI  - Droplet digital PCR using HER2/EIF2C1 ratio for detection of HER2 amplification
      in breast cancer tissues.
AB  - Breast cancers with amplification and overexpression of human epithelial growth
      factor receptor 2 (HER2) are associated with poor prognosis, and targeted for
      anti-HER2 therapy. Immunohistochemistry (IHC) and fluorescence in situ
      hybridization (FISH) are currently the recommended methods to asses HER2
      overexpression/amplification. Droplet digital PCR (ddPCR), a highly accurate
      method to quantify DNA copy number, is potentially a robust alternative for HER2
      diagnostics. In the FISH assay and most of previous ddPCR reports, chromosome 17
      centromere (CEP17) has been used as the reference control to determine HER2/CEP17
      ratio. Nevertheless, miss-classification could occur when HER2 is co-amplified
      with CEP17. To avoid this inherent defect, in the present study, we employed
      ddPCR assay using the human eukaryotic translation initiation factor 2C1 (EIF2C1)
      gene located at chromosome 1p34.3 as the reference control to quantify HER2 copy
      number in 31 frozen breast cancer tissues. HER2 status of these samples had been
      determined by FISH and classified as HER2-amplified and HER2-non-amplified breast
      cancers. The results showed that HER2 determined by ddPCR using HER2/EIF2C1 ratio
      was in good concordance with HER2 determined by FISH using HER2/CEP17 ratio, the
      concordance rate 87.1% (27/31), Kappa  = 0.719. The sensitivity and specificity
      of ddPCR assay was 90% (9/10) and 85.7% (18/21), respectively. The median
      HER2/EIF2C1 copy number ratio in HER2-amplified cancers (6.55, range 1.3-17.3)
      was significantly higher than in HER2-non-amplified cancers (1.05, range 0.6-3.6,
      p < 0.001). This study demonstrated that ddPCR using HER2/EIF2C1 ratio could
      accurately assess HER2 status in frozen breast cancer tissues. Thus, our findings
      warrant further studies into breast cancer with HER2-equivocal by IHC/FISH.

PMID- 30284064
TI  - Sugar-sweetened beverage consumption and incidence of breast cancer: the
      Seguimiento Universidad de Navarra (SUN) Project.
AB  - PURPOSE: Breast cancer (BC) incidence is increasing worldwide. Higher insulin
      resistance may potentially lead to an increased risk of BC. Sugar-sweetened
      beverages (SSB) are an acknowledged dietary factor that increases insulin
      resistance. However, the association between SSB and BC has not been widely
      explored. We evaluated the association between baseline consumption of SSB and
      the incidence of BC among relatively young women in a cohort of Spanish
      university graduates. METHODS: We evaluated 10,713 middle-aged, Spanish female
      university graduates (median age 33) from the Seguimiento Universidad de Navarra
      (SUN) cohort, initially free of BC. SSB consumption was collected at baseline
      using a validated 136-item semi-quantitative food-frequency questionnaire.
      Incidence of BC was confirmed by a trained oncologist using medical records. We
      fitted Cox regression models to assess the relationship between baseline
      categories of SSB consumption and the incidence of BC during follow-up. We
      stratified the analyses by menopausal status. RESULTS: During 106,189 person
      years follow-up, 100 incident cases of BC were confirmed. Among postmenopausal
      women, regular consumption of SSB was associated with a significantly higher
      incidence of BC (HR 2.12; 95% CI 1.02, 4.41) in the fully adjusted model,
      compared to women who never or seldom consumed SSB. No association was found
      among premenopausal women (HR 1.16; 95% CI 0.66, 2.07). CONCLUSIONS: Even though
      the number of cases was small, in this Mediterranean cohort, we observed a direct
      association between SSB consumption and BC risk among postmenopausal women.
      Nonetheless further larger longitudinal studies are needed to support this
      association.

PMID- 30284065
TI  - Effect of an egg ovalbumin-derived protein hydrolysate on blood pressure and
      cardiovascular risk in adults with a mildly elevated blood pressure: a randomized
      placebo-controlled crossover trial.
AB  - PURPOSE: While animal and in vitro data demonstrate vasodilatory effects of egg
      white-derived peptides, human studies are lacking. We investigated for the first
      time the effects of an egg ovalbumin-derived protein hydrolysate on blood
      pressure (BP) and cardiovascular risk. METHODS: A double-blind, placebo
      controlled randomized crossover trial was implemented in 75 adults aged 50-70
      years with systolic BP (130-<= 150 mmHg). Participants were randomized to an egg
      ovalbumin-derived protein hydrolysate (3 g/day) or placebo (3 g/day).
      Participants completed two 6-week periods separated by a 3-week washout. RESULTS:
      Data from 65 participants with a mean systolic BP (135.1 +/- 11 mmHg) were
      included. Mean office and central BP and arterial stiffness (assessed by carotid
      femoral pulse wave velocity (cfPWV) or pulse wave analysis (PWA)) did not change
      over time and no significant differences were observed between the egg protein
      hydrolysate and placebo groups (P > 0.05). Similarly, no significant effects of
      this egg ovalbumin-derived protein hydrolysate on blood lipid and glucose
      concentrations (P > 0.05) were observed. CONCLUSION: This is the first dietary
      intervention to investigate the effects of egg ovalbumin-derived protein
      hydrolysates on cardiovascular risk in humans. Despite promising findings from
      animal and in vitro studies, this RCT does not support the hypothesis that
      consumption of an egg ovalbumin-derived protein hydrolysate for 6 weeks in adults
      with a high-normal BP results in a reduction in BP or the modification of
      cardiovascular risk.

PMID- 30284066
TI  - Cereal fructan extracts alter intestinal fermentation to reduce adiposity and
      increase mineral retention compared to oligofructose.
AB  - PURPOSE: Intestinal fermentation of inulin-type fructans, including
      oligofructose, can modulate adiposity, improve energy regulation, and increase
      mineral absorption. We aimed to determine whether cereal fructans had greater
      effects on reducing adiposity and improving mineral absorption compared with
      oligofructose. METHODS: Thirty-two male Sprague-Dawley rats were randomly
      assigned to one of four dietary treatments that contained 0% fructan (control),
      or 5% fructan provided by oligofructose (OF), a barley grain fraction (BGF), or a
      wheat stem fraction (WSF). After 1 week on the diets, mineral absorption and
      retention was assessed. At 4 weeks, blood samples were collected for gut hormone
      analysis, adipose depots were removed and weighed, and caecal digesta was
      analyzed for pH and short-chain fatty acids (SCFA). RESULTS: The BGF and WSF, but
      not OF, had lower total visceral fat weights than the Control (p < 0.05). The
      fructan diets all lowered caecal pH and raised caecal digesta weight and total
      SCFA content, in comparison to the Control. Caecal propionate levels for OF were
      similar to the Control and higher for WSF (p < 0.05). Plasma peptide YY and
      glucagon-like peptide-1 levels were elevated for all fructan groups when compared
      to Control (p < 0.001) and gastric inhibitory peptide was lower for the WSF
      compared to the other groups (p < 0.05). The fructan diets improved calcium and
      magnesium retention, which was highest for WSF (p < 0.05). BGF and WSF in
      comparison to OF showed differential effects on fermentation, gut hormone levels,
      and adiposity. CONCLUSIONS: Cereal fructan sources have favorable metabolic
      effects that suggest greater improvements in energy regulation and mineral status
      to those reported for oligofructose.

PMID- 30284067
TI  - What attributes guide best practice for effective feedback? A scoping review.
AB  - There has been an observed increase in literature concerning feedback within the
      last decade, with the importance of feedback well documented. Current discourse
      promotes feedback as an interactive, dialogic process between the learner and the
      learning partner. While much has been written about effective feedback, less is
      known about key elements that support dialogic feedback. It is therefore
      important to investigate what is known about the elements that guide best
      practice for effective feedback. A scoping review of the extant literature
      following Arksey and O'Malley's methodology was conducted. A search of literature
      published in English identified sixty-one publications eligible for this review.
      Publications were representative of the international literature from both
      empirical and non-empirical sources. Feedback elements were extracted from the
      included publications and categorised into 11 core attributes. The attributes
      identified feedback as: being a process; criteria-based; requiring multiple forms
      and sources of data/evidence; needs to be desired by the recipient (i.e. invited
      and welcomed); timely; responsive to the learner (i.e. tailored to developmental
      needs/learning preferences of the learner); frequent; future-focussed; reciprocal
      (i.e. two-way); involves skilful interaction; and is multidimensional (i.e.
      engages the learner in more than one way). Despite the rhetoric on feedback as a
      'dialogic process', a gap remains in our understanding around what is required to
      engage the learner as an equal partner in the feedback process. Further research
      exploring the impact of specific aspects of the feedback process on practice is
      required.

PMID- 30284068
TI  - Contradictions in clinical teachers' engagement in educational development: an
      activity theory analysis.
AB  - Many medical universities offer educational development activities to support
      clinical teachers in their teaching role. Research has focused on the scope and
      effectiveness of such activities and on why individual teachers attend. However,
      systemic perspectives that go beyond a focus on individual participants are
      scarce in the existing literature. Employing activity theory, we explored how
      clinical teachers' engagement in educational development was affected by the
      systems they act within. Three focus groups were held with clinical teachers from
      different professions. A thematic analysis was used to map the contradictions
      between the systems that the participants were part of and the manifestations of
      these contradictions in the system of education. In our model, clinical teachers
      were part of three activity systems directed by the objects of patient care,
      research and education respectively. Contradictions arose between these systems
      as their objects were not aligned. This manifested through the enacted values of
      the academic hospital, difficulties establishing educational discussions in the
      clinical workplace, the transient nature of educational employments, and
      impediments to developing a teacher identity. These findings offer insights into
      the complexities of engaging in educational development as clinical teachers'
      priorities interact with the practices and values of the academic hospital,
      suggesting that attention needs to shift from individual teachers to developing
      the systems in which they work.

PMID- 30284069
TI  - A rare solitary fibrous tumor in the ischiorectal fossa: a case report.
AB  - BACKGROUND: A solitary fibrous tumor (SFT) is a rare mesenchymal tumor that
      occurs mostly in pleural sites, and an SFT occurring in the ischiorectal fossa is
      extremely rare. Because of the rarity, there are few reports detailing an SFT in
      the ischiorectal fossa. CASE PRESENTATION: A pararectal tumor was incidentally
      found in a 42-year-old man during a routine medical examination. The patient had
      no symptoms and no previous medical history. In the physical examination, a
      smooth-margined and hard elastic mass was felt, and in a digital rectal
      examination, the rectal mucosa appeared normal. A computed tomography (CT) scan
      showed a 5-cm, well-defined, solid mass in the left ischiorectal fossa. Contrast
      enhanced CT in the early phase showed intense heterogeneous enhancement that
      persisted during the delayed phase. T2-weighted images of magnetic resonance
      imaging yielded heterogeneous intermediate and low signal intensity. Intense
      arterial enhancement suggested a hypervascular nature, and persistent delayed
      enhancement and low signal bands on T2-weighted images suggested a fibrous
      component of the mass. An SFT was suspected. Most SFTs are benign but have
      malignant potential. Our patient did not hope for surgery if the tumor was
      benign; therefore, an ultrasound-guided transperineal core needle biopsy was
      performed to decide on a treatment strategy. Microscopic examination showed tumor
      cells appearing as spindle and fibroblast-like cells within a collagenous stroma.
      Immunohistochemistry identified CD34 and vimentin, supporting the diagnosis of an
      SFT. The patient consented to excision of the mass. He was placed in a prone
      jackknife position, and the tumor was removed transperineally using a posterior
      approach (modified Kraske procedure). The levator ani muscle, external sphincter
      muscles, and rectum were not involved and separated from the tumor. The tumor was
      successfully resected en bloc with no complications. Five uneventful days post
      surgery, the patient was discharged. There was no local recurrence during the
      year following surgery. CONCLUSION: Imaging findings reflect the tissue
      characterization such as hypervascularity and fibrous nature of SFTs. We have
      presented a rare case of an SFT in the ischiorectal fossa with useful imaging
      findings for diagnosis, treatment strategy, and successful surgical removal using
      a posterior approach.

PMID- 30284070
TI  - Structural and functional abnormalities in iron-depleted heart.
AB  - Iron deficiency (ID) is a common and ominous comorbidity in heart failure (HF)
      and predicts worse outcomes, independently of the presence of anaemia.
      Accumulated data from animal models of systemic ID suggest that ID is associated
      with several functional and structural abnormalities of the heart. However, the
      exact role of myocardial iron deficiency irrespective of systemic ID and/or
      anaemia has been elusive. Recently, several transgenic models of cardiac-specific
      ID have been developed to investigate the influence of ID on cardiac tissue. In
      this review, we discuss structural and functional cardiac consequences of ID in
      these models and summarize data from clinical studies. Moreover, the beneficial
      effects of intravenous iron supplementation are specified.

PMID- 30284071
TI  - A qualitative study of Realtor knowledge, attitudes, and practices related to
      radon health effects: implications for comprehensive cancer control.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related deaths in the
      United States, and radon exposure is the second leading risk factor. Fewer than
      25% of existing U.S. homes have been tested for radon, and only 5-10% of new
      homes use some form of radon prevention. OBJECTIVE: This qualitative study sought
      to determine radon-related knowledge, attitudes, and practices among Realtors to
      inform cancer control activities at local and state levels. METHODS: We conducted
      focus groups with Realtors in four states to collect information about knowledge,
      attitudes, and practices regarding radon. RESULTS: Realtors reported obtaining
      information on radon in similar ways, being aware of radon and its
      characteristics, and dealing with radon issues as a normal part of home sales.
      Differences in attitudes toward testing varied across states. Realtors in states
      with radon policies generally expressed more positive attitudes toward testing
      than those in states without policies. Radon mitigation was identified as an
      added expense to buyers and sellers. Realtors cited concerns about the
      reliability and credibility of mitigation systems and installers. CONCLUSIONS:
      These findings suggest that attitudes and practices vary among Realtors and that
      additional educational resources about radon as a cancer risk factor may be
      beneficial. When comprehensive cancer control programs update their plans, they
      may want to add objectives, strategies, or activities to reduce radon exposure
      and prevent lung cancer. These activities could include partnering with Realtors
      to improve their knowledge, attitudes, and practices about radon, as well as
      developing and distributing radon educational resources.

PMID- 30284072
TI  - A new case of the pilomatrixoma rare in the preauricular region and review of
      series of cases.
AB  - Pilomatrixoma is considered a rare benign tumor arising from the hair follicle,
      most common in the head and neck region, but it is rarely diagnosed on a clinical
      basis. This report describes a new case of giant pilomatrixoma in a 36-year-old
      female patient. The nodule was localized in the preauricular area on the right
      side, appearing as a slow-growing, fixed, painless, with a hardened consistency,
      unusual giant (4.5 cm). A cone-beam computed tomography (CBCT) examination showed
      a slightly hyperdense lesion, and fine-needle aspiration cytology (FNAC) revealed
      peripheral blood and mononucleated inflammatory cells. After enucleation of
      lesion, a diagnosis of pilomatrixoma was confirmed. The differential diagnosis of
      pilomatrixoma is broad, because its characteristics also can be found in other
      lesions common to the head and neck. Thus, a lesion in the head and neck,
      adherent to the skin, and well demarcated, mainly in the young and in females,
      should be suspected as pilomatrixoma.

PMID- 30284073
TI  - Investigating the Relationship Between Climate and Valley Fever
      (Coccidioidomycosis).
AB  - Valley fever (coccidioidomycosis) is a disease caused by inhalation of spores
      from the soil-dwelling Coccidioides fungal species. The disease is endemic to
      semiarid areas in the western USA and parts of Central and South America. The
      region of interest for this study, Kern County, California, accounts for
      approximately 14% of the reported valley fever cases in the USA each year. It is
      hypothesized that the weather conditions that foster the growth and dispersal of
      the fungus influence the number of cases in the endemic area. This study uses
      regression-based analysis to model and assess the seasonal relationships between
      valley fever incidence and climatic variables including concurrent and lagged
      precipitation, temperature, Palmer Drought Severity Index, wind speed, and PM10
      using data from 2000 to 2015. We find statistically significant links between
      disease incidence and climate conditions in Kern County, California. The best
      performing seasonal model explains up to 76% of the variability in fall valley
      fever incidence based on concurrent and antecedent climate conditions. Findings
      are consistent with previous studies, suggesting that antecedent precipitation is
      an important predictor of disease. The significant relationships found support
      the "grow and blow" hypothesis for climate-related coccidioidomycosis incidence
      risk that was originally developed for Arizona.

PMID- 30284074
TI  - Facile development of medium optimization for antibody production: implementation
      in spinner flask and hollow fiber reactor.
AB  - Most bio-industrial mammalian cells are cultured in serum-free media to achieve
      advantages, such as batch consistency, suspended growth, and simplified
      purification. The successful development of a serum-free medium could contribute
      to a reduction in the experimental variation, enhance cell productivity, and
      facilitate biopharmaceuticals production using the cell culture process.
      Commercial serum-free media are also becoming more and more popular. However, the
      cell line secrets its own recombinant product and has special nutritional
      requirements. How can the composition of the proprietary medium be adjusted to
      support the specific cell's metabolism and recombinant protein? This article uses
      statistical strategies to modify the commercial medium. A design of experiments
      is adopted to optimize the medium composition for the hybridoma cell in a serum
      free condition. The supplements of peptone, ferric citrate, and trace elements
      were chosen to study their impact on hybridoma growth and antibody production
      using the response surface methodology. The stimulatory effect of the developed
      formulation on hybridoma growth was confirmed by the steepest ascent path. The
      optimal medium stimulated the hybridoma growth and antibody production in three
      diverse systems: a static plate, an agitated spinner flask, and a hollow fiber
      reactor. The cells in the developed serum-free medium had a better antibody
      production as compared to that in the commercial medium in the hollow fiber
      reactor. Our results demonstrated that the facile optimization for medium and
      antibody production was successfully accomplished in the hybridoma cells.

PMID- 30284075
TI  - Effect of serum uric acid on cognition in patients with idiopathic REM sleep
      behavior disorder.
AB  - Idiopathic rapid eye movement sleep behavior disorder (iRBD) likely represents
      the prodromal stage of synucleinopathy. The present study investigated how levels
      of serum uric acid (UA) affect cognition and motor function in patients with
      iRBD. A total of 42 patients with iRBD and 45 healthy controls were included. All
      participants were given cognitive tests and motor assessments. Serum UA
      concentrations were measured. The patients were further divided into two groups
      (high or low UA) according to serum UA level. The level of serum UA was similar
      between the patients with iRBD and the healthy controls, whereas the patients
      showed impaired executive, memory, and visuospatial functions. The patients with
      low UA levels had longer durations of RBD. Lower scores involving attention,
      executive function, and language domain were also found in the patients with low
      UA, whereas the scores of the patients with high UA were similar to those of the
      healthy controls. Regarding memory domain, the low UA group had worse scores than
      the healthy controls, whereas the scores of high UA group fell between those of
      the low UA group and the healthy controls. Motor function was not affected in any
      of the groups. UA affects cognitive function but not motor function in patients
      with iRBD, which could contribute to its antioxidant and neuroprotective roles.

PMID- 30284076
TI  - Correlation between MCP-1-2518A/G polymorphism and the risk of Alzheimer's
      disease.
AB  - The -2518A/G polymorphism in monocyte chemotactic protein-1 (MCP-1) has been
      extensively investigated for association with Alzheimer's disease (AD); however,
      the results from different studies are inconsistent. The aim of this study was to
      draw an accurate conclusion of the association. All eligible case-control studies
      were searched in PubMed, Embase, Chinese National Knowledge Infrastructure, China
      Biological Medicine Databases, and Wanfang Databases. Eight case-control studies
      with a total of 2370 cases and 2413 controls were eligible to be included in this
      meta-analysis. The association was evaluated by calculating the odds ratios (ORs)
      with the corresponding 95% confidence intervals (CIs). Overall, there was no
      significant association between MCP-1-2518A/G polymorphism and AD risk in all
      genetic models (the allele model G vs. A: OR = 1.15, 95% CI 0.92-1.45, p = 0.22;
      the co-dominant model GG vs. AA: OR = 1.38, 95% CI 0.80-2.36, p = 0.25; the
      dominant model AG + GG vs. AA: OR = 1.14, 95% CI 0.89-1.46, p = 0.31; the
      recessive model GG vs. AG + AA: OR = 1.35, 95% CI 0.87-2.09, p = 0.18). In
      subgroup analysis by ethnicity, a significant difference was not detected in both
      Caucasians and Asians. In allele model (G vs. A), the required sample size of
      31858 was calculated by applying trial sequential analysis. Cumulative z curve is
      always below the trial sequential monitoring boundary and is nominally
      statistically significant (Z = 1.96). A consistent result was obtained in other
      genetic models. In summary, the present meta-analysis suggests that MCP-1-2518A/G
      polymorphism may not be associated with genetic susceptibility of AD in general
      population, but the association remains indeterminate due to the insufficient
      evidence.

PMID- 30284077
TI  - Dogs and wolves do not differ in their inhibitory control abilities in a non
      social test battery.
AB  - Being able to inhibit certain behaviours is of clear advantage in various
      situations. In particular, it has been suggested that inhibitory control plays a
      role in problem-solving and cooperation. Interspecific differences in the
      capacity for inhibitory control have been attributed to social and ecological
      factors, while one additional factor, namely domestication, has received only
      little attention so far. Dogs are an interesting species to test the effects of
      socio-ecological factors and also the influence of domestication on inhibitory
      control abilities. While dogs might have been selected for enhanced inhibition
      skills during domestication, the predictions derived from their socio-ecological
      background are reversed. Wolves are cooperative hunters and breeders, while dogs
      predominately scavenge and raise their young alone, accordingly, it would be
      predicted that dogs show impaired inhibitory control abilities since they no
      longer rely on these coordinated actions. To test these hypotheses, we assessed
      inhibitory control abilities in dogs and wolves raised and kept under similar
      conditions. Moreover, considering the problem of context-specificity in
      inhibitory control measures, we employed a multiple-test-approach. In line with
      previous studies, we found that the single inhibition tests did not correlate
      with each other. Using an exploratory approach, we found three components that
      explained the variation of behaviours across tests: motivation, flexibility, and
      perseveration. Interestingly, these inhibition components did not differ between
      dogs and wolves, which contradicts the predictions based on their socio
      ecological backgrounds but also suggests that at least in tasks with minimal
      human influence, domestication did not affect dogs' inhibitory control abilities,
      thus raising questions in regard to the selection processes that might have
      affected inhibitory control abilities during the course of domestication.

PMID- 30284078
TI  - Prevalence of fibromyalgia in physicians in training: a cross-sectional study.
AB  - The prevalence of fibromyalgia (FM) in physicians in training (PIT) in Saudi
      Arabia is unknown. The aim of this study is to evaluate the prevalence of FM in
      PIT using different screening tools and factors associated with its development.
      We also aimed at evaluating the level of agreement and correlation between
      screening tools. This was a cross-sectional study conducted in a single academic
      institution. PIT were invited to fill three questionnaires: Fibromyalgia Rapid
      Screening tool (FirST), Fibromyalgia Survey Questionnaire (FSQ), and London
      Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ). A total of 182
      PIT completed the questionnaire. They were predominantly males (57.1%), single
      (56.0%), and at resident level (86.7%). The median age was 28 (interquartile
      range = 4). The average number of house-calls/month was 3.2 (SD = 2.3). The
      prevalence of FM using the FirST, FSQ, and LFESSQ was 6.0%, 8.2%, and 11.6%,
      respectively. Six (3.3%) fulfilled the three criteria concurrently. After
      adjusting for different variables using the FSQ, PIT with family history of FM
      had 23.6 times the odds for testing positive (95% CI = 3.12, 178.37), and every
      extra house-call/month was associated with a 50% increase in the odds for testing
      positive for FM (95% CI = 1.00, 2.25). Percent agreement between tools was high
      (all > 86%). Results for kappa coefficient showed moderate agreement between FSQ
      scores and each of FirST and LFESSQ. There was poor agreement between FirST and
      LFESSQ. FM is prevalent among PIT. There is a high percent agreement and poor to
      moderate correlation between the screening tools used.

PMID- 30284079
TI  - Physical activity levels after hip and knee joint replacement surgery: an
      observational study.
AB  - Usual care after hip or knee joint replacement does not adequately address the
      problem of low physical activity levels. We aimed to determine whether exercise
      delivered in a group setting in the early stage of outpatient rehabilitation
      influenced self-reported physical activity levels after hip or knee joint
      replacement. A case series of 79 participants referred to a 6-week outpatient
      orthopaedic exercise group after total hip or knee replacement were evaluated
      using the International Physical Activity Questionnaire (IPAQ) short form.
      Physical function was evaluated using Osteoarthritis Research Society
      International (OARSI) recommended performance-based tests (30 s Chair Stand Test,
      40 m Fast Pace Walk Test, Stair Climb Test, Timed Up and Go Test, 6 Minute Walk
      Test). Measures were assessed at admission, discharge and 6 weeks after group
      discharge. Non-parametric analysis was conducted for IPAQ scores. Analysis of
      functional measures was conducted with linear mixed models with time modelled as
      a repeated measure. Standard multiple regression and correlation analysis were
      conducted. Fifty-four participants completed the study. Self-reported activity
      levels improved significantly at program discharge but not at 6-week follow-up.
      All performance-based measures improved significantly at program discharge. Fast
      paced walking and 6 Minute Walk Test measures continued to improve at 6-week
      follow-up. Group dynamics present in an outpatient rehabilitation exercise
      program may increase physical activity levels during group participation but not
      after group cessation. Performance in all functional measures improved at group
      discharge.

PMID- 30284081
TI  - Prevalence and Correlates of Reporting Difficulty Taking Antiretroviral Treatment
      Among HIV-Positive Illicit Drug Users in Vancouver, Canada: A Longitudinal
      Analysis.
AB  - People living with HIV who use illicit drugs continue to experience high rates of
      suboptimal treatment outcomes from antiretroviral therapy (ART). Although
      previous studies have identified important behavioural, social and structural
      barriers to ART adherence, the effects of patient-level factors have not been
      fully evaluated. Thus, we sought to investigate the prevalence and correlates of
      reporting ART was difficult to take among a cohort of illicit drug users in
      Vancouver, Canada. We accessed data from the AIDS Care Cohort to evaluate
      Exposure to Survival Services (ACCESS), an ongoing prospective cohort of HIV
      positive illicit drug users linked to comprehensive HIV clinical monitoring
      records. We used generalized linear mixed-effects modeling to identify factors
      longitudinally associated with periods in which individuals reported they found
      ART difficult to take. Between December 2005 and May 2014, 746 ART-exposed
      illicit drug users were recruited and contributed at least one study interview.
      Finding ART hard to take was reported by 209 (28.0%) participants at baseline,
      and 460 (61.7%) participants throughout the study period. Patients ingesting a
      greater daily pill count (adjusted odds ratio [AOR] = 1.12 per pill, 95%
      confidence interval [CI] 1.08-1.17) and experiencing barriers to healthcare (AOR
      = 1.64, 95% CI 1.34-2.01) were more likely to report difficulty taking ART.
      Patients less likely to report satisfaction with their HIV physician (AOR = 0.76,
      95% CI 0.58-1.00) and achieve a non-detectable HIV viral load (AOR = 0.62, 95% CI
      0.51-0.74) were more likely to report finding ART hard to take. In this community
      recruited cohort of ART-exposed illicit drug users, a substantial proportion
      reported they found HIV treatment hard to take, which was clearly linked to
      higher dissatisfaction with healthcare experiences and, most importantly, a lower
      likelihood of experiencing optimal virologic outcomes. Our findings reveal a
      number of opportunities to improve HIV treatment experiences and outcomes for
      people who use illicit drugs, including the use of treatment regimens with lower
      pill burdens, as well as reducing barriers to healthcare access.

PMID- 30284080
TI  - A phase II study of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1,
      followed by gastrectomy with D2 lymph node dissection for high-risk advanced
      gastric cancer: results of the KDOG1001 trial.
AB  - BACKGROUND: The prognosis of patients with gastric cancer with bulky node
      metastasis, linitis plastica (type 4), or large ulcero-invasive-type tumors (type
      3) remains poor. We conducted a phase II study to evaluate the safety and
      efficacy of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 (DCS) for
      establishing a new treatment modality that improves prognosis. METHODS: Patients
      received up to four 28-day cycles of DCS therapy (docetaxel at 40 mg/m2,
      cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks)
      followed by gastrectomy with D2 nodal dissection. S-1 chemotherapy was
      administered for 1 year after surgical resection. The primary endpoint was the
      percentage of complete resections of the primary tumor with clear margins (R0
      resection). The planned sample size was 40; this was calculated based on an
      expected R0 rate of 85% and a threshold R0 rate of 65%, with a one-sided alpha of
      5% and a power of 90%. RESULTS: Between 2010 and 2017, 40 patients were enrolled.
      The R0 resection rate was 90%. The most common grade 3 or 4 adverse events during
      DCS therapy were leukocytopenia (27.5%), neutropenia (55.0%), and hyponatremia
      (22.5%). The most common grade 3 or 4 surgical morbidity was pancreatic fistula
      (12.5%); mortality was 0%. The pathological response rate was 57.5% with a grade
      3 histological response rate of 8%. CONCLUSIONS: Neoadjuvant chemotherapy with
      DCS was feasible and showed a sufficient R0 resection rate. A future study with a
      sufficient follow-up period should confirm survival outcomes.

PMID- 30284083
TI  - Substance P and pain chronicity.
AB  - Substance P (SP) is a highly conserved member of the tachykinin peptide family
      that is widely expressed throughout the animal kingdom. The numerous members of
      the tachykinin peptide family are involved in a multitude of neuronal signaling
      pathways, mediating sensations and emotional responses (Steinhoff et al. in
      Physiol Rev 94:265-301, 2014). In contrast to receptors for classical
      transmitters, such as glutamate (Parsons et al. in Handb Exp Pharmacol 249-303,
      2005), only a minority of neurons in certain brain areas express neurokinin
      receptors (NKRs) (Mantyh in J Clin Psychiatry 63:6-10, 2002). SP is also
      expressed by a variety of non-neuronal cell types such as microglia, as well as
      immune cells (Mashaghi et al. in Cell Mol Life Sci 73:4249-4264, 2016). SP is an
      11-amino acid neuropeptide that preferentially activates the neurokinin-1
      receptor (NK1R). It transmits nociceptive signals via primary afferent fibers to
      spinal and brainstem second-order neurons (Cao et al. in Nature 392:390-394,
      1998). Compounds that inhibit SP's action are being investigated as potential
      drugs to relieve pain. More recently, SP and NKR have gained attention for their
      role in complex psychiatric processes. It is a key goal in the field of pain
      research to understand mechanisms involved in the transition between acute pain
      and chronic pain. The influence of emotional and cognitive inputs and feedbacks
      from different brain areas makes pain not only a perception but an experience
      (Zieglgansberger et al. in CNS Spectr 10:298-308, 2005; Trenkwaldner et al. Sleep
      Med 31:78-85, 2017). This review focuses on functional neuronal plasticity in
      spinal dorsal horn neurons as a major relay for nociceptive information.

PMID- 30284085
TI  - Cell biological profiling of reprogrammed cancer stem cell-like colon cancer
      cells maintained in culture.
AB  - Cancer stem cells (CSCs) are specific targets for therapeutic applications, but
      the rarity of CSCs within tumors makes the isolation of CSCs difficult. To
      overcome these problems, we generated CSCs in vitro using established
      reprogramming techniques. We transduced four previously established reprogramming
      factors, Oct3/4, Sox2, Klf4, and L-myc, into the colon cancer cell lines LoVo and
      OUMS-23, and investigated the biological characteristics of these lines. Tra-1
      60+ cells were obtained from reprogrammed induced pluripotent stem (iPS) cell
      like colonies and showed CSC properties, including colony formation, maintenance
      of colonies by repeated passages, and feeder cell dependency, as well as
      increased expressions of CSC markers such as CD133 and ALDH1. The CSC-like cells
      showed increased chemoresistance to 5-fluorouracil and elevated tumorigenicity
      upon transplantation into kidneys of immune-deficient mice. These tumors shifted
      to a poorly differentiated stage with many atypical cells, cytoplasmic mucin, and
      focal papillary components, with demonstrated dedifferentiation. The principal
      component analysis from DNA microarrays showed that though both cell lines moved
      to iPS cells after reprogramming, they were not completely identical to iPS
      cells. Significantly elevated gene expression of Decorin and CD90 was observed in
      CSC-like cells. Together, these results show that reprogramming of cancer cells
      produced not pluripotent stem cells but CSC-like cells, and these findings will
      provide biological information about genuine CSCs and help establish new CSC
      targeted therapies.

PMID- 30284086
TI  - Forced expression of mouse progerin attenuates the osteoblast differentiation
      interrupting beta-catenin signal pathway in vitro.
AB  - Nuclear protein, lamin A, which is a component of inner membrane on nucleoplasm,
      plays a role in nuclear formation and cell differentiation. The expression of
      mutated lamin A, termed progerin, causes a rare genetic aging disorder,
      Hutchinson-Gilford progeria syndrome, which shows abnormal bone formation with
      the decrease in a number of osteoblasts and osteocytes. However, exact molecular
      mechanism how progerin exerts depressive effects on osteogenesis has not been
      fully understood. Here, we created mouse lamin A dC50 cDNA encoding progerin that
      lacks 50 amino acid residues at C-terminus, transfected it in mouse preosteoblast
      like MC3T3-E1 cells, and examined the changes in osteoblast phenotype. When lamin
      A dC50-expressed cells were cultured with differentiation-inductive medium,
      alkaline phosphatase (ALP) activity and mRNA levels of major osteoblast markers,
      type I collagen (Col1), bone sialoprotein (BSP), dentine matrix protein 1 (DMP1),
      and Runx2 were significantly decreased, and no mineralized nodules were detected
      as seen in control cells expressing empty vector. In the culture with
      mineralization-inductive medium, mRNA levels of BSP, osteocalcin, DMP1, Runx2,
      and osterix were strongly decreased parallel with loss of mineralization in lamin
      A dC50-expressed cells, while mineralized nodules appear at 21 days in control
      cells. Furthermore, lamin A dC50 expression was depressed nuclear localization of
      beta-catenin with the decrease of GSK-3beta phosphorylation level. These results
      suggest that lamin A dC50 depresses osteoblast differentiation in both early and
      late stages, and it negatively regulates beta-catenin activity interacting with
      GSK-3beta in cytoplasm.

PMID- 30284087
TI  - Generation of clinical-grade red blood cells from human umbilical cord blood
      mononuclear cells.
AB  - A xeno-free method for ex vivo generation of red blood cells (RBCs) is attempted
      in order to replicate for large-scale production and clinical applications. An
      efficient milieu was formulated using injectable drugs substituting the animal
      derived components in the culture medium. Unfractionated mononuclear cells
      isolated from human umbilical cord blood were used hypothesizing that the
      heterogeneous cell population could effectively contribute to erythroid cell
      generation. The strategy adopted includes a combination of erythropoietin and
      other injectable drugs under low oxygen levels, which resulted in an increase in
      the number of mature RBCs produced in vitro. The novelty in this study is the
      addition of supplements to the medium in a stage-specific manner for the
      differentiation of unfractionated umbilical cord blood mononuclear cells (MNCs)
      into erythropoietic lineage. The erythropoietic lineage was well established by
      day 21, wherein the mean cell count of RBCs was found to be 21.36 +/- 0.9 * 108
      and further confirmed by an upregulated expression of CD235a+ specific to RBCs.
      The rationale was to have a simple method to produce erythroid cells from
      umbilical cord blood isolates in vitro by mitigating the effects of multiple
      erythroid-activating agents and batch to batch variability.

PMID- 30284088
TI  - Photobiomodulation effect on the proliferation of adipose tissue mesenchymal stem
      cells.
AB  - The use of mesenchymal stem cells (MSCs) in tissue engineering has been
      extensively investigated. The greater the proliferation of this cellular group,
      the greater the regenerative and healing capacity of the tissue to which they
      belong. In this context, photobiomodulation (PBM) is an efficient technique in
      proliferation of distinct cell types. However, its parameters and mode of action
      are still unclear and require further investigation. This study aimed to evaluate
      the PBM action with different energies in MSCs of adipose tissue (hASCs). We used
      hASCs, seeded in 24-well plates, with 3 * 104 cells per well, in culture media.
      We used a total of four experimental groups, one with hASCs and simulated PBM and
      three other groups, which received PBM irradiation at 24, 48, and 72 h, with a
      660-nm laser and power of 40 mW and energy of 0.56, 1.96, and 5.04 J. We
      performed analyses of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromidefor) and trypan blue to evaluate cell proliferation and viability, 1 h
      after PBM irradiation. Software Graph PadPrism 7.0 was used. Intergroup
      comparisons were performed with ANOVA two-way and we used the Tukey post hoc
      test. Mitochondrial activity evaluated by MTT revealed the statistical difference
      in the first 24 h for group with more high energy when compared to control group;
      and in the 72 h for two irradiated groups when compared to the control group. The
      trypan blue test showed significant differences at the end of the experiment for
      two irradiated groups LG1 (4.52 * 104 +/- 0.2) and LG2 (4.85 * 104 +/- 0.8), when
      compared to the control group (1.87 * 104 +/- 0.7). Both tests failed to be
      statistically different at the end of the experiment for groups LG1 and LG2 and
      observed a reduction in cellular mitochondrial growth and activity for group LG3.
      We conclude that PBM with energy close to 0.56 and 1.96 J promote proliferation
      of hASCs, and higher energy, such as 5.04 J, can be harmful.

PMID- 30284084
TI  - Basement membranes in the cornea and other organs that commonly develop fibrosis.
AB  - Basement membranes are thin connective tissue structures composed of organ
      specific assemblages of collagens, laminins, proteoglycan-like perlecan,
      nidogens, and other components. Traditionally, basement membranes are thought of
      as structures which primarily function to anchor epithelial, endothelial, or
      parenchymal cells to underlying connective tissues. While this role is important,
      other functions such as the modulation of growth factors and cytokines that
      regulate cell proliferation, migration, differentiation, and fibrosis are equally
      important. An example of this is the critical role of both the epithelial
      basement membrane and Descemet's basement membrane in the cornea in modulating
      myofibroblast development and fibrosis, as well as myofibroblast apoptosis and
      the resolution of fibrosis. This article compares the ultrastructure and
      functions of key basement membranes in several organs to illustrate the
      variability and importance of these structures in organs that commonly develop
      fibrosis.

PMID- 30284090
TI  - Clinical Predictors of Delayed Discharges in Inpatient Mental Health Settings
      Across Ontario.
AB  - Delayed discharges constitute an ongoing issue in psychiatric facilities. This
      study examined clinical predictors of 30-day delayed discharges in all designated
      inpatient mental health units within Ontario, Canada. Data for 76,184 inpatient
      episodes were obtained from 68 psychiatric facilities between 2011 and 2013. Risk
      factors for delayed discharges were analyzed using multivariate logistic
      regression. Indicators of functional, social, and cognitive impairment positively
      predicted delayed discharges, while symptoms of mental illness were inversely
      related. Policy makers and mental health care practitioners may utilize early
      predictors of delayed discharges to introduce treatment interventions and
      policies that reduce the risk of delays in mental health settings.

PMID- 30284089
TI  - Shared decision making in pharmacotherapy decisions, perceived by patients with
      bipolar disorder.
AB  - BACKGROUND: Shared decision making has been promoted as standard care, but there
      has been debate on the possible types. On the one hand, there is a more
      'instrumental'/objective approach focused on the exchange of information, but an
      'interpersonal'/subjective patient involvement has been suggested as well. In
      this study we aim to investigate this further by assessing both actual and
      perceived patient involvement in medical decisions. METHODS: Eighty-one
      consultations between patients with bipolar disorder and their clinicians were
      observed and scored using the OPTION scale. Afterwards, the patients' experienced
      involvement was explored with the SDM-Q-9. Furthermore, several patient
      characteristics were gathered. Correlations between the scores were examined.
      RESULTS: The clinicians scored on average 34.6 points on the OPTION scale. In
      contrast, patients scored on average 77.5 points on the SDM-Q-9, suggesting that
      patients felt more involved in the consultation than was observable. CONCLUSION:
      Our patients with bipolar disorder feel involved in pharmacotherapy decisions,
      but this is not scored in objective observations. Our data suggest that there are
      implicit, interpersonal aspects of patient involvement in shared decision making,
      a concept that deserves further attention and conceptualisation.

PMID- 30284091
TI  - MP-3 measurement of retinal sensitivity in macular hole area and its predictive
      value on visual prognosis.
AB  - PURPOSE: To explore a measuring method for retinal sensitivity in macular hole
      area by Microperimeter-3 (MP-3) and evaluate its predictive value on visual
      prognosis. METHODS: This was a case series study including 44 eyes of 44 patients
      with idiopathic macular hole. Retinal sensitivity inside and 0.5 degree outside
      the macular hole margin was measured, and its mean value was defined as macular
      hole sensitivity (MHS). Best-corrected visual acuity (BCVA), minimum diameter of
      macular hole (MD), IS/OS defect diameter, retinal sensitivity in 8 degrees and 2
      degrees were also recorded preoperatively and 4 months after operation. RESULTS:
      All macular holes were closed after surgery. BCVA was significantly improved from
      1.06 +/- 0.39 at baseline to 0.31 +/- 0.24 at 4 months postoperatively (P <
      0.001). Meanwhile, MHS was also significantly improved from 12.02 +/- 3.74 dB at
      baseline to 20.72 +/- 4.00 dB at 4 months postoperatively (P < 0.001). MD,
      preoperative IS/OS defect diameter, preoperative BCVA, preoperative retinal
      sensitivity in 8 degrees and 2 degrees, and preoperative MHS were all correlated
      with postoperative BCVA at 4 months, but only preoperative MHS showed liner
      relationships to postoperative BCVA at 4 months by multivariate stepwise linear
      analysis. CONCLUSIONS: Macular hole sensitivity by MP-3 could reflect the change
      of central retinal function after successful macular hole surgery. Compared to
      preoperative retinal sensitivity in 8 degrees and 2 degrees, preoperative macular
      hole sensitivity is a better predictor for visual prognosis.

PMID- 30284092
TI  - Surgical outcomes of 27-gauge and 25-gauge vitrectomy day surgery for
      proliferative diabetic retinopathy.
AB  - PURPOSE: To compare postoperative outcomes of 27-gauge (G) and 25-G vitrectomy
      conducted as day surgery for proliferative diabetic retinopathy (PDR). METHODS:
      One hundred eighty-five consecutive PDR patients (185 eyes) who underwent primary
      vitrectomy (27-G in 64 eyes, 25-G in 121 eyes) were analyzed. RESULTS: The 27-G
      and 25-G groups did not differ significantly in preoperative Early Treatment
      Diabetic Retinopathy Study (ETDRS) score, age, or preoperative intraocular
      pressure. The proportions of simultaneous cataract surgery (27-G vs. 25-G: 59.4%
      vs. 62.4%) and air-filled eyes (76.6% vs. 85.1%) were not significantly different
      between two groups. Both groups showed significant improvement in ETDRS score at
      postoperative 1, 3, and 6 months (all, P < 0.0001). Mean gain in ETDRS score from
      baseline was apparently better in 27-G group than in 25-G group at 1, 3, and 6
      months, but there were no significant differences (1 month: 20.3 vs. 13.1
      letters, P = 0.0703; 3 months: 22.9 vs. 17.5 letters, P = 0.1561; 6 months: 24.3
      vs. 19.3 letters, P = 0.3313). Operation time was apparently longer for 27-G
      vitrectomy, but there was no significant difference (54.0 vs. 51.1 min, P =
      0.3676). The same was observed for postoperative intraocular pressure at
      postoperative day 1 (19.7 vs. 18.1 mmHg, P = 0.1353). Incidence of postoperative
      retinal detachment (1.6% vs. 0.8%) and reoperation due to vitreous hemorrhage
      (6.3% vs. 6.6%) was not different between two groups. CONCLUSIONS: The 27G system
      is as safe and as useful as the 25G system when used for PDR and can be expected
      to achieve earlier recovery of postoperative visual acuity.

PMID- 30284094
TI  - Do Home-Based Psychiatric Services for Patients in Medico-Social Institutions
      Reduce Hospitalizations? Pre-Post Evaluation of a French Psychiatric Mobile Team.
AB  - World Health Organization recommends the implementation of alternatives to full
      time hospitalizations. Psychiatric home-care has known a worldwide development in
      the last 20 years. The psychiatric mobile team for social and medico-social
      institutions in Saint-Etienne, France, (Equipe mobile d'intervention en
      etablissements Sociaux et Medico-sociaux, ESMS) aims to support professionals
      from medico-social housing institutions (MSHI) in order to maintain people in
      housing. The objective of the study was to evaluate the efficiency of home-based
      interventions to reduce hospitalizations and improve collaboration between
      psychiatric hospital facilities and MSHI. We used a pre-post study design. A same
      cohort of patients living in a MSHI one year before intervention and one year
      after implementation of the ESMS was studied. Hospitalizations were compared
      between the two periods. A survey was conducted for qualitative evaluation among
      professionals in MHSI. Sixty-three patients were included. Most patients suffered
      from psychotic disorders (71%). We found a significant decrease in the mean
      number of admissions per year from 2,06 to 1,48 (Wilcoxon signed rank test; df64;
      p = 0,01). Mobile-team interventions included answering phone calls, home visits,
      coordination meetings, or clinical interviews with patients in inpatient and
      outpatient services, with an average of 9,3 interventions per patient (SD =
      11,4). ESMS was evaluated as "essential" for 73% of 11 professionals from MSHI
      who answered the questionnaire in May 2017. Assertive Community Treatment and
      Crisis Resolution Teams are the most studied home-care models in psychiatry. Our
      results tend to show the efficiency of mobile-team interventions in MSHI, to
      enhance partnerships.

PMID- 30284093
TI  - Improving the fluorometric determination of the cancer biomarker 8-hydroxy-2'
      deoxyguanosine by using a 3D DNA nanomachine.
AB  - The authors describe a fluorometric method for improving the determination of the
      cancer biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG). A nicking endonuclease
      (NEase)-powered 3-D DNA nanomachine was constructed by assembling hundreds of
      carboxyfluorescein-labeled single strand oligonucleotides (acting as signal
      reporter) and tens of swing arms (acting as single-foot DNA walkers) on a gold
      nanoparticle (AuNP). The activity of this DNA nanomachine was controlled by
      introducing the protecting oligonucleotides. In the presence of aptamer against 8
      OHdG, the protecting oligonucleotides are removed from the swing arms by toehold
      mediated strand displacement reaction. In the next step, detached DNA walker
      hybridizes to the labelled DNA so that the DNA nanomachine becomes activated.
      Special sequences of signal reporter in the formed duplex can be recognized and
      cleaved by NEase. As a result, the DNA walker autonomously and progressively
      moves along the surface of the AuNP, thereby releasing hundreds of signal
      reporters and causing a rapid increase in green fluorescence. This 3-D
      nanomachine is highly efficient because one aptamer can release hundreds of
      signal reporters. These unique properties allowed for the construction of a DNA
      nanomachine-based method for sensitively detecting 8-OHdG in concentrations as
      low as 4 pM. This is three orders of magnitude lower compared to previously
      reported methods. Graphical abstract Schematic of a fluorometric method for
      determination of the cancer biomarker 8-hydroxy-2'-deoxyguanosine. A nicking
      endonuclease powered 3D-DNA nanomachine was used to improve the sensitivity.
      Limit of detection is three orders of magnitude lower than reported methods.

PMID- 30284095
TI  - Introducing Mother Baby Connections: a model of intensive perinatal mental health
      outpatient programming.
AB  - Perinatal mental health problems, experienced by 15-20% of women, are a
      significant public health issue associated with adverse effects among
      childbearing women; yet only 20-25% receive adequate treatment. There has been a
      recent proliferation of intensive perinatal day treatment programs in the United
      States. To meet this need in the greater Philadelphia area, we introduce Mother
      Baby Connections (MBC), an innovative interdisciplinary, attachment-focused,
      intensive, outpatient perinatal mental health program recently launched at Drexel
      University. The purpose of this paper is to (1) present an overview of MBC, its
      theoretical framework for services, and its evidence-based components,
      highlighting the unique factors that differentiate this program from traditional
      outpatient treatment, and (2) present clinical outcome data utilizing scores from
      reliable and valid scales, including enrollment to discharge outcomes from 20
      months of MBC operation. In sum, outcomes for 20 predominantly minority women
      with complete measures showed significant improvements in maternal depression
      symptom severity, maternal functioning, birth trauma symptoms, perceived stress,
      parenting stress, and emotional regulation. Effect sizes were medium to large
      (i.e., 0.42-2.00). We conclude that MBC is a viable model for tailored intensive
      outpatient treatment to foster maternal mental health and functioning during the
      perinatal period.

PMID- 30284096
TI  - In vitro culture supplementation of EGF for improving the survival of equine
      preantral follicles.
AB  - Folliculogenesis is a process of development and maturation of the ovarian
      follicles, being essential for the maintenance of fertility. In in vivo
      conditions, 99.9% of the follicles of an ovary do not ovulate and undergo
      atresia. In order to minimize this loss and to clarify the existing mechanisms, a
      technique was developed that allows for the in vitro follicular development. The
      objective of this study was to evaluate the effects of different epidermal growth
      factor (EGF) concentrations on the in vitro culturing of equine preantral
      follicles. Ovaries (n = 10) were collected from a local slaughterhouse of mares
      in seasonal anestrus, washed with 70% alcohol and PBS, and transported. The inner
      portion of the ovary was divided into 11 fragments of approximately 3 * 3 * 1 mm.
      A fragment of each ovary was immediately fixed in Bouin (control group). The
      remaining 10 fragments were individually cultured for 2 and 6 d. The medium was
      supplemented with different concentrations of EGF (0, 10, 50, 100, and 200
      ng/mL). After cultivation, the fragments were processed and classified according
      to the developmental stage and morphology. In total, 1065 slides containing 6105
      tissue sections were evaluated. Within 2 d of culture, there was a higher
      proportion of intact follicles at the EGF concentrations of 0 and 100 ng/mL (p >
      0.05). After 6 d of culture, only the EGF concentration of 100 ng/mL demonstrated
      a difference when compared to the other treatments (0, 10, 50 and 200 ng/mL of
      EGF, p > 0.05). There was follicular development after 2 d at all EGF
      concentrations. Thus, we suggest that EGF promotes follicular survival in equines
      at a concentration of 100 ng/mL in in vitro cultures of ovarian fragments for 2
      d. In addition, we suggest that EGF promotes follicular survival in equines at a
      concentration of 100 ng/mL in situ cultivation.

PMID- 30284097
TI  - Effects of continuous positive airway pressure in patients at high risk of
      obstructive sleep apnea during propofol sedation after spinal anesthesia.
AB  - In patients with obstructive sleep apnea, short-term use of a continuous positive
      airway pressure mask improves oxygenation, decreases the apnea-hypopnea index,
      and reduces hemodynamic instability. In this study, we investigated the effects
      of use of a continuous positive airway pressure mask in patients at high risk of
      obstructive sleep apnea during propofol sedation after spinal anesthesia. Forty
      patients who underwent propofol sedation after spinal anesthesia for
      transurethral bladder or prostate resection with a STOP-Bang score of 3 or more
      were enrolled in this study. Patients were randomly divided into two groups: a
      simple oxygen mask group (n = 20) and a continuous positive airway pressure mask
      group (n = 20). After spinal anesthesia, propofol was injected at a target
      concentration of 1.3 mcg/ml via a target concentration control injector.
      ApneaLinkTM was applied to all patients. Patients in the simple oxygen mask group
      were administered oxygen at a rate of 6 L/min through a simple facial mask.
      Patients in the CPAP mask group were connected to a pressurizer, and oxygen (6
      L/min, 5-15 cm H2O) was administered. Blood pressure, heart rate, respiratory
      rate, and oxygen saturation were recorded preoperatively, after spinal
      anesthesia, and every 5 min after the injection of propofol to observe
      hemodynamic changes. Apnea-hypopnea index was estimated using ApneaLinkTM. There
      were no significant differences in hemodynamic changes between the two groups.
      Apnea-hypopnea index was significantly reduced in the continuous positive airway
      pressure mask group compared to the simple facial mask group. Application of a
      continuous positive airway pressure mask in a patient at high risk of obstructive
      sleep apnea can lower the incidence of obstructive sleep apnea during sedation
      without a significant effect on hemodynamic stability.

PMID- 30284098
TI  - Non-invasive real-time autonomic function characterization during surgery via
      continuous Poincare quantification of heart rate variability.
AB  - Heart rate variability (HRV) provides an excellent proxy for monitoring of
      autonomic function, but the clinical utility of such characterization has not
      been investigated. In a clinical setting, the baseline autonomic function can
      reflect ability to adapt to stressors such as anesthesia. No monitoring tool has
      yet been developed that is able to track changes in HRV in real time. This study
      is a proof-of-concept for a non-invasive, real-time monitoring model for
      autonomic function via continuous Poincare quantification of HRV dynamics.
      Anonymized heart rate data of 18 healthy individuals (18-45 years) undergoing
      minor procedures and 18 healthy controls (21-35 years) were analyzed. Patients
      underwent propofol and fentanyl anesthesia, and controls were at rest. Continuous
      heart rate monitoring was carried out from before aesthetic induction to the end
      of the surgical procedure. HRV components (sympathetic and parasympathetic) were
      extracted and analyzed using Poincare quantification, and a real-time assessment
      tool was developed. In the patient group, a significant decrease in the
      sympathetic and parasympathetic components of HRV was observed following
      anesthesia (SD1: p = 0.019; SD2: p = 0.00027). No corresponding change in HRV was
      observed in controls. HRV parameters were modelled into a real-time graph. Using
      the monitoring technique developed, autonomic changes could be successfully
      visualized in real-time. This could provide the basis for a novel, fast and non
      invasive method of autonomic assessment that can be delivered at the point of
      care.

PMID- 30284099
TI  - Identification of C-Terminal Binding Protein 1 as a Novel NMDA Receptor
      Interactor.
AB  - A new N-methyl D aspartate neurotransmitter receptor interacting protein has been
      identified by yeast two-hybrid screening of a mouse brain cDNA library. C
      terminal binding protein 1 (CtBP1) was shown to associate with the intracellular
      C-terminal regions of the N-methyl D aspartate receptor subunits GluN2A and
      GluN2D but not with GluN1-1a cytoplasmic C-terminal region. In yeast mating
      assays using a series of GluN2A C-terminal truncations, it was demonstrated that
      the CtBP1 binding domain was localized to GluN2A 1157-1382. The GluN2A binding
      domain was identified to lie within the CtBP1 161-224 region. CtBP1 co
      immunoprecipitated with assembled GluN1/GluN2A receptors expressed in mammalian
      cells and also, in detergent extracts of adult mouse brain. Co-expression of
      CtBP1 with GluN1/GluN2A resulted in a significant decrease in receptor cell
      surface expression. The family of C-terminal binding proteins function primarily
      as transcriptional co-repressors. However, they are also known to modulate
      intracellular membrane trafficking mechanisms. Thus the results reported herein
      describe a putative role for CtBP1 in the regulation of cell surface N-methyl D
      aspartate receptor expression.

PMID- 30284100
TI  - Screening and diagnosis of oral cancer: a critical quality appraisal of clinical
      guidelines.
AB  - OBJECTIVES: To assess the quality of clinical practice guidelines (CPGs) on
      screening and diagnosis of oral cancer and to describe the characteristics of
      their recommendations. MATERIALS AND METHODS: We systematically searched EMBASE,
      MEDLINE, CPG' websites, and dentistry and oncology scientific societies to
      identify CPGs that were related to screening and diagnosis of oral cancer. The
      quality of selected CPGs was independently assessed by four appraisers using the
      Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. The
      inter-appraiser agreement was assessed. We performed a descriptive analysis of
      the recommendations included in the selected CPGs. RESULTS: Eight CPGs were
      selected. The overall agreement among reviewers was considered very good (ICC:
      0.823; 95% CI: 0.777-0.861). The median scores of the six AGREE II domains were
      as follows: "scope and purpose" 97.9% (IQR: 96.2-100.0%); "stakeholder
      involvement" 86.1% (IQR: 69.8-93.1%); "rigor of development" 75.3% (IQR: 64.2
      94.3%); "clarity of presentation" 91.7% (IQR: 82.6-94.4%); "applicability" 53.1%
      (IQR: 19.3-74.2%); and "editorial independence" 83.3% (IQR: 67.2-93.8%). Four
      CPGs were assessed as "recommended", four "recommended with modifications", and
      none "not recommended". Twenty-three recommendations were provided, mostly with a
      low or very low level of evidence. CONCLUSION: The methodological quality of CPGs
      on screening and diagnosis of oral cancer is moderate. The "applicability" domain
      scored the lowest. Most recommendations were based on a low o very low level of
      evidence. CLINICAL RELEVANCE: Greater efforts are needed to provide healthcare
      based on high-quality evidence-based CPGs in this field.

PMID- 30284101
TI  - Effect of anaerobic cure of self-etch adhesive on degree of conversion and shear
      bond strength.
AB  - OBJECTIVE: The main aim was to evaluate the effect of postponing the curing of
      the adhesive layer until the first layer of composite resin is applied-hereby
      oxygen-inhibited layer (OIL) formation and its detrimental effect on the degree
      of conversion (DC) of self-etch adhesives should be prevented. For this purpose,
      the degree of conversion and shear bond strength of four current market self-etch
      adhesives were evaluated, assessing the effect of curing the adhesives
      anaerobically and then under two different thicknesses of composite resin, and
      compare this to the samples cured alone and in air. MATERIALS AND METHODS: The
      degrees of conversion were obtained by attenuated total reflectance-Fourier
      transform infrared (ATR-FTIR) spectroscopy, after the samples were prepared on a
      glass slide. The samples were either light-cured in air or anaerobically under a
      clear matrix strip alone, under 2 mm of cured composite resin or under 4 mm of
      cured composite resin. To determine the shear bond strength (SBS), extracted
      molars were halved and set in acrylic. Prefabricated cured cylinders of composite
      resin (TPH 3, 2.4 mm in diameter) of two different lengths are placed over the
      adhesives under the following conditions: light-cured conventionally (2-mm-long
      cylinder) and light-cured anaerobically under the uncured end of the piece of
      composite resin (using both 2- and 4-mm-long cylinders as separate treatments).
      After another incubation for 24 h at 37  degrees C, the samples were subjected to
      shearing using the Bisco Shear Bond Strength Tester. RESULTS: The degree of
      conversion of the one-step self-etch adhesives was not statistically different
      when cured anaerobically under a clear matrix strip or cured anaerobically under
      2 mm of composite resin. These results were greater than those cured under 4 mm.
      Shear bond strength between samples cured in air and anaerobically were similar
      under 2 mm of composite resin tubes, while those cured anaerobically under 4 mm
      of resin showed lower shear bond strength. CONCLUSION: When cured anaerobically,
      one-step self-etch adhesives show a greater degree of conversion and no
      significant difference in degree of conversion and shear bond strength when
      compared to those cured in air under the same thickness of composite resin.
      CLINICAL RELEVANCE: The results obtained from DC and SBS analysis show promise in
      placing the uncured adhesive under the composite resin and curing both the
      adhesive and restoration material simultaneously.

PMID- 30284102
TI  - Comparison of linear and volumetric measurements obtained from periodontal
      defects by using cone beam-CT and micro-CT: an in vitro study.
AB  - OBJECTIVES: To assess linear and volumetric measurement accuracy of periodontal
      defects (class 2 furcation, fenestration, dehiscence, and three-wall intrabony
      defect) by using CBCT and micro-CT images obtained at different voxel sizes.
      MATERIAL AND METHODS: We created 66 periodontal defects in human dry mandibles.
      Images of teeth with defects were taken by Planmeca Promox 3D Max (CBCT) at voxel
      sizes of 0.2 and 0.075 mm and super-argus PET/CT (micro-CT) at voxel sizes of
      0.12 and 0.06 mm. All defects were then linearly (depth, width, and height) and
      volumetrically measured by 3D-DOCTOR software. Differences between voxels were
      assessed by Wilcoxon signed rank test. Bland-Altman limits of agreement and ICCs
      were calculated to assess agreement between the methods. Significance was set at
      p < 0.05. RESULTS: Volumes measured by micro-CT (0.12-0.06 mm) were higher than
      those of CBCT (0.2-0.075 mm) measurements regardless of the voxel size. ICC
      between micro CT and CBCT methods was found to be statistically significant for
      all types of defects in terms of volume (p < 0.001), height (p < 0.05), width (p
      < 0.001), and depth measurements (p < 0.001). CONCLUSION: CBCT provides useful
      information regarding linear and volumetric measurement of periodontal defects in
      vitro. CLINICAL RELEVANCE: Size and volume of periodontal defects may play an
      important role in the determination of the most appropriate treatment plan and
      disease prognosis along with outcome assessment.

PMID- 30284103
TI  - Supplementation of biotin to sperm preparation medium enhances fertilizing
      ability of spermatozoa and improves preimplantation embryo development.
AB  - PURPOSE: Motility of spermatozoa helps not only in planning the type of
      infertility treatment but also directly reflects the success rate in assisted
      reproductive technology (ART). Previously, biotin, a water-soluble vitamin, has
      been shown to increase the motility and longevity of cryopreserved human
      spermatozoa. The present study was designed to understand the molecular basis of
      the beneficial effects of presence of biotin in sperm wash medium on early embryo
      development. METHODS: The effect biotin supplementation to sperm wash medium on
      the sperm parameters were assessed in swim-up fraction of normozoospermic and
      asthenozoospermic ejaculates collected from infertile men. Fertilization and
      early embryo development was studied using Swiss albino mice. RESULTS: Even
      though both biotin and pentoxifylline (PTX) enhanced the motility of spermatozoa
      from normozoospermic and asthenozoospermic samples, biotin group exhibited higher
      in vitro survival. Using mouse model, we observed that presence of biotin or PTX
      in sperm wash medium improved the fertilization rate and blastocyst rate compared
      to control. Blastocysts from these groups had significantly higher total cell
      number (P < 0.01) and lower apoptotic index. In silico target prediction revealed
      that GTPase HRas (HRas), tyrosine-protein phosphatase nonreceptor type 1 (PTP1B),
      and glucokinase are the probable targets for biotin. Solution-state Nuclear
      Magnetic Resonance (NMR) studies confirmed that biotin interacts both with human
      HRas and PTP1B. CONCLUSION: Our results indicate that presence of biotin in sperm
      wash medium can improve the fertilization potential and preimplantation embryo
      development and can be considered as a safe alternate to PTX.

PMID- 30284104
TI  - Increased frequency of impaired fasting glucose and isolated systolic
      hypertension in Paget's disease of bone.
AB  - PURPOSE: Scanty data about glucose metabolism and hypertension have been reported
      in Paget's disease of bone (PDB) to be related with increased cardiovascular
      mortality. The aim of the present study was to evaluate glucose and blood
      pressure levels in PDB, looking for their association with disease severity.
      METHODS: We performed an observational cross-sectional study in 54 patients with
      PDB and 54 age, sex and BMI-matched controls. Glucose and blood pressure levels
      and parameters of bone and mineral metabolism were assessed. RESULTS: Patients
      with PDB showed increased glucose levels (6.3 +/- 1.7 vs 5.3 +/- 1.4 mmol/l, p <
      0.001) and prevalence of impaired fasting glucose (14.8%, 5.3-24.3 vs 1.9%, 0
      5.4, p < 0.02) as well as enhanced systolic blood pressure (145.9 +/- 21.3 vs
      132.9 +/- 18.9 mmHg, p < 0.005), pulse pressure (69.6 +/- 20.0 vs 56.0 +/- 16.9
      mmHg, p < 0.01) and prevalence of isolated systolic hypertension (46.3%, 33.0
      59.6 vs 16.7%, 6.7-26.6, p < 0.003) in comparison to controls. Moreover, we found
      a positive association of (1) glucose levels with ionized calcium and bone
      alkaline phosphatase; (2) both systolic and pulse pressure with total and bone
      alkaline phosphatase (p < 0.05). By multiple linear regression analysis (R2 =
      0.26; p < 0.05) serum ionized calcium correlated with glucose levels (beta =
      0.44; p < 0.04), after adjusting for age and BMI. CONCLUSIONS: Our study shows
      increased fasting glucose, systolic and pulse pressure levels as well as enhanced
      prevalence of impaired fasting glucose and isolated systolic hypertension in PDB,
      potentially accounting for increased cardiovascular mortality. Furthermore, our
      findings suggest high serum calcium and/or increased bone alkaline phosphatase as
      a link between PDB and cardio-metabolic disorders.

PMID- 30284105
TI  - Grape seed proanthocyanidin extract and insulin prevents cognitive decline in
      type 1 diabetic rat by impacting Bcl-2 and Bax in the prefrontal cortex.
AB  - It is frequently accepted that grape seed proanthocyanidins (GSPs) are efficient
      antioxidants and beneficial in improving cognitive functions. However, diabetes
      (T1DM)-associated declines in learning and memory and the possibilities of GSPs
      in overcoming this loss needs to be examined. The present study was designed to
      examine the correlation, if one exists, between cognitive behavior and neuronal
      survival in the prefrontal cortex (PFC) in streptozotocin (STZ)-induced diabetic
      Wistar rats as well as to further clarify whether the correlation exists. Also
      this study aimed to determine whether neurological structural changes in the PFC
      and pancreatic beta-cells can be restored by grape seed proanthocyanidin extract
      (GSPE). At the end of 8 weeks, cognitive tests that rats given supplementation of
      GSPE and insulin had greater improvement in their spatial learning and memory
      skills and improved neuronal survival in the PFC and pancreatic beta-cells
      compared to rats supplemented with either insulin or GSPE alone. Expression of
      Bax in the PFC was increased in the diabetic rats while Bcl-2 expression was
      decreased, and GSPE and insulin treatment reversed the expression of apoptotic
      proteins. Our findings on GSPE, a natural product, as a form of adjuvant therapy
      together with insulin treatment is suggestive of the existence of synergism
      between the two in attenuating diabetic complications in the pancreas and PFC.

PMID- 30284106
TI  - What Is the Non-calcifying Langerhans Cell-Rich Variant of Calcifying Epithelial
      Odontogenic Tumor?

PMID- 30284107
TI  - Design, synthesis and in vitro evaluation of a Dopa-organoboron compound that
      acts as a bladder relaxant through non-catecholamine receptors.
AB  - Bladder relaxation through drug administration is an interesting topic in
      medicinal and combinatorial chemistry. In fact, compounds targeting catecholamine
      receptors [dopamine receptors and beta-adrenergic receptors (betaAR) expressed in
      the bladder] are among the compounds commonly employed for this purpose. In
      particular, recent investigations have tended to focus on the beta3-adrenoceptor
      (beta3AR) as a target in the treatment of urinary incontinence and other
      disorders. However, organoboron compounds have been suggested as potent and
      efficient agents on these drug targets. In this work, through a docking study, we
      identified the parameters that induce a theoretical improvement in the affinity
      and activity of the organoboron compounds on the catecholamine receptors
      expressed in the bladder. Then, the identified potential drug, a boron-containing
      dopa-derivative named DPBX-L-Dopa, was synthesized and characterized. This
      compound induces a relaxation on the smooth muscle of the rat bladder, behaving
      as a weak relaxant compared to isoproterenol but with similar efficacy to BRL377,
      a selective beta3AR agonist. However, unexpectedly, this effect was not blocked
      by propranolol or haloperidol at the concentrations at which they are able to
      block the catecholamine receptors in bladder tissue. In view of these results,
      the effect of DPBX-L-Dopa compound on the alpha 1 adrenergic receptors (alpha1AR)
      of aorta of the rats was also explored; however, no response of the tissue to
      this compound was obtained. The possible mechanisms of the action of this
      compound were explored and are discussed further.

PMID- 30284108
TI  - Inhibitory Potential against Digestive Enzymes Linked to Obesity and Type 2
      Diabetes and Content of Bioactive Compounds in 20 Cultivars of the Peach Fruit
      Grown in Poland.
AB  - The presented study provides important insights on the health properties of
      Prunus persica fruit related to their polyphenol and carotenoid profiles,
      antioxidant capacity and in vitro potential to inhibit enzymes relevant to type 2
      diabetes (alpha-amylase, alpha-glucosidase) and obesity (pancreatic lipase)
      management. Such results have not been published so far. The study showed
      substantial differences in the chemical composition of peach fruit depending on
      the cultivar. At the same time, it demonstrated some common features of selected
      cultivars - the varieties with light flesh ('Spring Time'; 'Madison') were
      characterized by a high content of phenolic acids and flavonols, thus exhibiting
      high activity against alpha-amylase, while the yellow varieties with high content
      of carotenoids ('Harrow Diamond'; 'Harrow Beauty') showed high inhibitory
      activity toward porcine pancreatic lipase. Finally, it has been shown that peach
      fruit is an interesting raw material with a varied chemical composition and
      nutritional value, especially with high inhibitory potential against digestive
      enzymes linked to obesity and type 2 diabetes, strongly determined by the
      cultivar.

PMID- 30284110
TI  - Enhanced Confinement of Terahertz Surface Plasmon Polaritons in Bulk Dirac
      Semimetal-Insulator-Metal Waveguides.
AB  - A subwavelength terahertz plasmonic waveguide based on bulk Dirac semimetal (BDS)
      insulator-metal (BIM) structure is investigated, which indicates that there is an
      optimized frequency range with the better confinement as well as lower loss. A
      broadband mode confinement up to lambda0/15 with a relatively low loss of 1.0
      dB/lambda0 can be achieved. We also show that two silicon ribbons introduced into
      the BIM waveguide can form a dynamically tunable filter tailoring terahertz
      surface plasmon polaritons in deep-subwavelength scale, which can be further
      exploited for the design of ultra-compact THz plasmonic devices with dynamical
      tunability. Our results may also provide potential applications in optical
      filtering.

PMID- 30284111
TI  - A PPy/ZnO functional interlayer to enhance electrochemical performance of
      lithium/sulfur batteries.
AB  - To enhance the electrochemical performance of the lithium/sulfur batteries, a
      novel interlayer was prepared by coating the slurry of PPy/ZnO composite onto the
      surface of a separator. Owing to a three-dimensional hierarchical network
      structure, PPy/ZnO composite serves as a polysulfide diffusion absorbent that can
      intercept the migrating soluble polysulfides to enhance the electrochemical
      performance of the Li/S batteries. The specific capacity of the cell with PPy/ZnO
      interlayer remained at 579 mAh g-1 after 100 cycles at 0.2 C. This interlayer can
      provide novel avenues for the commercial applications of Li/S batteries.

PMID- 30284109
TI  - Nutraceutical, Physicochemical, and Sensory Properties of Blue Corn polvorones, a
      Traditional Flour-Based Confectionery.
AB  - Blue corn is an anthocyanin-rich material that can be used in the preparation of
      baking products. The aim of this work was to evaluate the physicochemical,
      nutraceutical, and sensory properties of polvorones (a traditional flour-based
      confectionery) made with whole blue-corn flour. All samples showed similar
      bromatological composition, but polvorones from whole blue-corn flour had a
      higher phenolics (837.1 mg gallic acid/kg) and anthocyanins (373.0 mg cyanidin-3
      glucoside/kg) content, which exerted an influence on their higher antioxidant
      activity compared with wheat flour-based laboratory and commercial samples. The
      transformation of raw blue-corn flour into polvorones produced the degradation of
      some acylated anthocyanins into non-acylated forms. The substitution of wheat
      flour with whole blue-corn flour enhanced overall acceptability, as well as the
      color and flavor of polvorones. Our findings demonstrated that it is possible to
      use whole blue corn in the formulation of polvorones with more health beneficial
      properties and better consumer acceptability than refined wheat products.

PMID- 30284112
TI  - Analysis of the regulatory mechanism of deoxynivalenol production using omics.
AB  - Fusarium species are plant pathogens that produce various mycotoxins. Here, the
      regulatory mechanism of deoxynivalenol production in Fusarium asiaticum was
      analyzed using proteomic, metabolomic and transcriptomic methods. F. asiaticum
      was induced to produce deoxynivalenol by adding agmatine to the culture medium.
      Subsequently, metabolites of the glycolysis system were increased but mRNAs of
      the corresponding proteins were not up regulated. We speculated that this
      phenomenon was due to the up regulation of the 6-fructokinase and pyruvate kinase
      proteins, which are key enzymes of glycolysis. We discuss the relationship of
      metabolism with the regulation of deoxynivalenol production in F. asiaticum.

PMID- 30284113
TI  - Robotic-assisted laparoscopic apical suspension: description of the spiral
      technique.
AB  - This video's objective was to describe our spiral technique and surgical steps of
      robotic-assisted laparoscopic apical suspension (RALAS) in the treatment of
      patients with symptomatic apical vaginal prolapse. A 70-year-old Caucasian woman,
      gravida 3, para 2 had symptomatic pelvic organ prolapse (POP) apical/anterior
      stage III. At pelvic ultrasound evaluation, the uterus was small and normal
      appearing of adnexa bilaterally. She failed pessaries and is sexually active. The
      most relevant complaints were vaginal bulging and pressure. She denied urinary
      incontinence. During the surgery, we used (1) 3-0, V-LocTM (Covidien) and we
      reinforced these absorbable sutures with (2) 2-0, GORE-TEX(r) Suture (Gore
      Medical). The Si da Vinci Surgical System was used with 4 arms and 5 trocars
      configuration, docked on the patient's left side. On the right/left apical
      support, we used V-Loc and Gore-Tex and these provided the initial 2 points
      suspension on the uterosacral ligaments (USL). We like to attach the left to the
      right USL. We then developed the space between the bladder and vagina and proceed
      with a plication of the pubocervical fascia with V-loc sutures. Two anterior
      apical support sutures were taken from the vagina to the transversalis fascia on
      the anterior abdominal wall and then hid behind the bladder peritoneum. The
      tension of these sutures was maintained with Hem-o-lock (TeleFlex) and LAPRA-TY
      (Ethicon). With the spiral technique, we secured these sutures through
      aponeurosis of abdominal muscle inside-outside-inside using a Carter-Thomason
      (Cooper Surgical) laparoscopic port closure system. This technique may provide a
      better long-term support for the anterior apical compartment.

PMID- 30284115
TI  - A cost of musical training? Sensorimotor flexibility in musical sequence
      learning.
AB  - We report an experiment that tested the flexibility of sensorimotor learning in
      sequence production. Nonpianists and pianists learned simple melodies by ear
      under one of two auditory feedback conditions: one with normal pitch mapping
      (higher pitches to the right) and one with an inverted (reversed) mapping. After
      learning, both groups played melodies from memory while experiencing each
      feedback condition. Both groups exhibited sensorimotor learning and produced
      fewer errors at test while hearing the feedback used during training as opposed
      to the alternate feedback condition. However, learning was unstable for pianists
      who learned melodies with an inverted feedback condition, who produced more
      errors at test than pianists who learned melodies with normal-pitch mapping.
      Acquiring musical skill may therefore constrain subsequent sensorimotor
      flexibility.

PMID- 30284116
TI  - A Simon-like effect in Go/No-Go tasks performed in isolation.
AB  - The present study was conducted to decipher whether a spatial correspondence
      effect can emerge in Go/No-Go tasks (cSE, in reference to Donders' type c task)
      performed in isolation (participant alone in the cubicle). To this aim, a single
      participant was centrally positioned in front of a device and was required to
      respond by a hand key-press to the color of the stimulus. Half the participants
      were seated in front of a table equipped with only one response key and the other
      half in front of a table equipped with two response keys (one active and the
      other one useless). Using a substantial number of subjects (48) and trials (960),
      the present study revealed a numerically small but statistically reliable cSE.
      This result contrasts with referential coding predictions and suggests that the
      representation of a concurrently active response is not a prerequisite for the
      cSE to emerge. Moreover, the presence of a second response button in the
      participant's peripersonal space exerted no measurable influence on the cSE. The
      lack of statistical power of numerous previous studies may explain why the cSE
      has often been considered to be nil.

PMID- 30284117
TI  - Prevalence of Early Childhood Caries in India - A Systematic Review.
AB  - Early Childhood Caries (ECC) is a serious public health problem in developed as
      well as developing nations, with high prevalence among children around the world.
      This systematic review of the national literature was undertaken to document the
      prevalence of Early Childhood Caries. Studies evaluating the prevalence of Early
      Childhood Caries (ECC) in the Indian population were investigated. The method
      under evaluation was the use of a caries experience index to calculate the
      prevalence of ECC. An extensive literature search was done in the following
      databases: PubMed, IndMED and Cochrane upto June 2016. A modified version of the
      Newcastle-Ottawa Scale for cross-sectional studies was used for assessment of the
      quality of the studies. A systematic literature search yielded 503 publications
      from the various databases searched. Based on the inclusion and exclusion
      criteria, the final number of included studies were 54. Among the included
      studies, 19 studies were carried out in the state of Karnataka. Analysis of all
      the included studies revealed the overall prevalence of ECC in India to be 49.6%.
      Andhra Pradesh was found to have the highest prevalence of ECC at 63%, and the
      lowest prevalence was reported in Sikkim (41.92%). This review has reported a
      high prevalence of ECC in India. None of the states reported prevalence below
      40%. The government should identify ECC as a national priority which requires
      significant attention.

PMID- 30284114
TI  - Patient and provider communication about employment following a cancer diagnosis.
AB  - PURPOSE: Cancer treatment can precipitate functional limitations that restrict
      survivors' ability to work. Yet, it is unclear whether healthcare providers
      discuss the potential for employment limitations with their patients. We assessed
      the frequency of patient-provider communication about employment, from the
      perspectives of survivors, and examined whether receiving a treatment summary was
      associated with employment communication. METHODS: Cancer survivors who were
      working at diagnosis were identified from the Health Information National Trends
      Survey-4, conducted in 2014 (n = 290). Separate multivariable regression analyses
      examined the associations between survivor characteristics and employment
      communication and receipt of a treatment summary and employment communication.
      RESULTS: Among cancer survivors who were working at diagnosis, 62.69% (95% CI
      54.42-70.95) reported discussing employment with any healthcare provider at any
      time since diagnosis. Younger cancer survivors and those more recently treated
      were more likely to ever have employment discussions. Survivors who received a
      treatment summary were also more likely to ever discuss employment with any
      healthcare provider than survivors who did not receive a treatment summary (OR =
      3.47, 95% CI 1.02-11.84). CONCLUSIONS: Approximately two thirds of cancer
      survivors who were working at diagnosis ever discussed employment with a
      healthcare provider. Thus, for a sizable portion of cancer survivors, the
      potential impact of cancer on employment is never discussed with any healthcare
      provider. IMPLICATIONS FOR CANCER SURVIVORS: Efforts are needed to proactively
      screen patients for cancer-related work limitations, empower patients to discuss
      employment concerns with their healthcare providers, and develop interventions
      that support survivors' goals for working throughout treatment and recovery.

PMID- 30284118
TI  - Correction to: Agreement Between Body Composition Assessed by Bioelectrical
      Impedance Analysis and Doubly Labeled Water in Obese Women Submitted to Bariatric
      Surgery : Body Composition, BIA, and DLW.
AB  - The name of author Michele Novaes Ravelli was misspelled in the original article 
      it is correct here.

PMID- 30284119
TI  - Correction to: How Common is Statin Use in the Oldest Old?
AB  - In Section 4.3 "Factors Associated with Statin Use in the Oldest Old".

PMID- 30284121
TI  - Poly (D, L-lactide-co-glycolide)-phospholipid nanocarrier for efficient delivery
      of macular pigment lutein: absorption pharmacokinetics in mice and
      antiproliferative effect in Hep G2 cells.
AB  - Lutein has various biological activities, its application in food and pharma
      industries are limited due to poor aqueous solubility, stability, and
      bioavailability. To achieve various benefits, lutein-poly (lactic-co-glycolic
      acid) (PLGA)-phospholipid (PL) nanocapsules were prepared. Lutein-PLGA NCs (+PL)
      were synthesized, characterized and its bioavailability was studied in vitro and
      in vivo. The cellular uptake and anti-proliferative activity were analyzed in Hep
      G2 cells. The mean size and zeta value of lutein-PLGA NCs (+PL) were 140 +/- 6 nm
      and - 44 mV. The amorphous nature of lutein in PLGA NCs (+PL) was confirmed by
      XRD and DSC. In vitro lutein release kinetics showed an initial burst followed by
      sustainable release up to 86%. In vitro bioavailability showed 62.7% higher
      lutein bioaccessibility than lutein in free form. The AUC of lutein after single
      oral dose of lutein-PLGA NCs (+PL) revealed 3.91-fold (plasma), 2.89-fold
      (liver), and 3.12-fold (eyes) higher absorption than the control (mixed
      micelles). The IC50 of lutein-PLGA NCs (+PL) in Hep G2 cells at 72 h was 4.5 MUM
      as opposed to 23.4 MUM for lutein in free form. Thus, results reveal that PL
      added to PLGA NCs helps in enhancing the solubility which in turn resulted in its
      better bioavailability and bioefficacy.

PMID- 30284122
TI  - Carbohydrate-restricted diet promotes skin senescence in senescence-accelerated
      prone mice.
AB  - This study used senescence-accelerated prone mice (SAMP8) to examine the effects
      of a carbohydrate-restricted diet on aging and skin senescence, to determine how
      long-term carbohydrate restriction affects the aging process. Three-week-old male
      SAMP8 mice were divided into three groups after 1 week of preliminary feeding:
      one was given a controlled diet, the other was given a high-fat diet, and the
      third was given a carbohydrate-restricted diet. Ad libitum feeding was
      administered until the mice reached 50 weeks of age. Before the end of the test
      period, a grading test was used to evaluate visible aging in the mice. After the
      test period, serum and skin samples in mice were obtained and submitted for
      analysis. As a result, the grading test demonstrated that there was significant
      progression of visible aging in the carbohydrate-restricted group, as well as a
      decreased survival rate. Histological examination of the skin revealed that the
      epidermis and dermis in the carbohydrate-restricted group had become thinner.
      Analysis of the mechanisms involved demonstrated an increase in serum interleukin
      6, aggravated skin senescence, inhibition of skin autophagy and activation of
      skin mTOR. Therefore, this study proved that a carbohydrate-restricted diet
      promoted skin senescence in senescence-accelerated mice.

PMID- 30284120
TI  - The Role of Deprescribing in Older Adults with Chronic Kidney Disease.
AB  - Older adults with chronic kidney disease (CKD) often experience polypharmacy, a
      recognized predictor of prescribing problems including inappropriately dosed
      medications, drug-drug and drug-disease interactions, morbidity and mortality.
      Polypharmacy is also associated with nonadherence, which leads to recurrent
      hospitalizations and poorer hemodialysis outcomes in CKD patients. Further
      complicating medication management in this vulnerable population are the
      physiologic changes that occur with both age and CKD. This guide for pharmacists
      and prescribers offers considerations in medication evaluation and management
      among older adults with CKD. Careful prescribing with the aid of tools such as
      the American Geriatrics Society Beers Criteria can support safe medication use
      and appropriate prescribing. Polypharmacy may be systematically addressed through
      'deprescribing,' an evidence-based process that enables identification and
      elimination of unnecessary or inappropriate medications. Detailed guidance for
      deprescribing in older adults with CKD has not been published previously. We
      highlight three specific targets for medication optimization and deprescribing in
      older adults with CKD: (1) proton pump inhibitors, (2) oral hypoglycemic agents,
      including newer classes of agents, and (3) statins. These medication classes have
      been chosen as they represent three of the most commonly prescribed classes of
      medications in the United States. For each area, we review considerations for
      medication use in older adults with CKD and provide strategies to avoid, modify,
      or discontinue these medications when clinically indicated. By utilizing
      deprescribing techniques, pharmacists are well positioned to help decrease the
      medication burden in older adults with CKD, thereby potentially reducing the risk
      of morbidity and mortality associated with polypharmacy.

PMID- 30284123
TI  - Opioid Activity in the Locus Coeruleus Is Modulated by Chronic Neuropathic Pain.
AB  - Pain affects both sensory and emotional aversive responses, often provoking
      depression and anxiety-related conditions when it becomes chronic. As the opioid
      receptors in the locus coeruleus (LC) have been implicated in pain, stress
      responses, and opioid drug effects, we explored the modifications to LC opioid
      neurotransmission in a chronic constriction injury (CCI) model of short- and long
      term neuropathic pain (7 and 30 days after nerve injury). No significant changes
      were found after short-term CCI, yet after 30 days, CCI provoked an up-regulation
      of cAMP (cyclic 5'-adenosine monophosphate), pCREB (phosphorylated cAMP response
      element binding protein), protein kinase A, tyrosine hydroxylase, and electrical
      activity in the LC, as well as enhanced c-Fos expression. Acute mu opioid
      receptor desensitization was more intense in these animals, measured as the
      decline of the peak current caused by [Met5]-enkephalin and the reduction of
      forskolin-stimulated cAMP produced in response to DAMGO. Sustained morphine
      treatment did not markedly modify certain LC parameters in CCI-30d animals, such
      as [Met5]-enkephalin-induced potassium outward currents or burst activity and c
      Fos rebound after naloxone precipitation, which may limit the development of some
      typical opioid drug-related adaptations. However, other phenomena were impaired
      by long-term CCI, including the reduction in forskolin-stimulated cAMP
      accumulation by DAMGO after naloxone precipitation in morphine dependent animals.
      Overall, this study suggests that long-term CCI leads to changes at the LC level
      that may contribute to the anxiodepressive phenotype that develops in these
      animals. Furthermore, opioid drugs produce complex adaptations in the LC in this
      model of chronic neuropathic pain.

PMID- 30284124
TI  - From Inner Speech to Mind-Wandering: Developing a Comprehensive Model of Inner
      Mental Activity Trajectories.
AB  - The objective of this work was to develop a comprehensive model of inner mental
      activity's trajectories. For this purpose, a review of updated research was
      conducted on the wandering mind topic - a phenomenon that has been recently
      conceptualized and that has become a focus of interest in cognitive sciences -
      alongside early psychological postulates on the inner speech phenomenon that were
      brought back to the surface of scientific literature. In summary, this article
      presents a reformulation of the spontaneous thought model by Andrews-Hanna et al.
      (2017), broadening its scope to approach inner mental activity in all its forms
      and transitions. It is concluded that modern cognitive research has overlooked
      the full complexity of different types and forms of consciousness' expressions,
      understanding them as isolated phenomena and sub-dimensioning their trajectories
      during the flow of experience. This, mainly, due to a scarce incorporation of
      temporality and morphology to current theoretical models. It is proposed that
      cognitive acts described in modern research (spontaneous, controlled,
      involuntary, etc.) are, in synthesis, different symbolic and expressive natures
      of inner mental activity or thought phenomenon, which current literature has
      failed to understand as a whole. This article constitutes a contribution to
      future theoretical and experimental research that seeks out to explore the nature
      of thought and its development during a cognitive act.

PMID- 30284125
TI  - Vaccine coverage of children in care of the child welfare system.
AB  - OBJECTIVE: To assess vaccine coverage for a cohort of children who have been in
      the care of the child welfare system compared to children in the general
      population. METHODS: This retrospective cohort study used population-based
      administrative health data for a 2008 birth cohort of children from Alberta,
      Canada. We assessed coverage at ages 2 (n = 44,206) and 7 (n = 42,241) for three
      vaccines with different administration schedules for children in care (at any
      period before the age of assessment) and those who had never been in care,
      comparing them using risk differences and relative risks (RRs). We similarly
      assessed coverage for children not in care who shared characteristics of children
      in care. RESULTS: At age two, vaccination coverage for children in care ranged
      from 54.3% to 81.4%, depending on vaccine. In comparison, coverage for those not
      in care ranged from 74.2% to 87.4%. At age seven, coverage for children in care
      ranged from 53.1% to 65.3%, compared to 76.6% to 83.4% for those not in care. For
      all vaccines at both ages, the risk for being under-vaccinated was higher for
      children in care (e.g., diphtheria, pertussis, tetanus, polio, Haemophilus
      influenzae type b at age 7: RR 2.01, 95% confidence interval [CI] (1.74-2.32).
      Even for children not in care who had characteristics similar to children in
      care, we found children in care had lower coverage. CONCLUSION: Children in care
      have consistently lower vaccine coverage than children not in care. Policies and
      practices should promote optimal access to vaccination for these children.

PMID- 30284126
TI  - Clinical and Demographic Evaluation According to MEFV Genes in Patients with
      Familial Mediterranean Fever.
AB  - The present study examined the relationship between clinical findings and
      mutation analyses in children with Familial Mediterranean Fever (FMF) in the
      inner Black Sea region of Turkey. This retrospective, cross-sectional study
      included patients with FMF who were evaluated between 2007 and 2015. FMF was
      diagnosed according to the Tel Hashomer criteria. FMF mutations were analyzed
      using a Real-time PCR System (Roche Diagnostics, Mannheim, Germany), and patients
      were classified into three groups according to allele status. The most common
      symptom was abdominal pain (99%, n = 197). The most frequent mutations were M694V
      and R202Q. Chest pain was reported more often in patients homozygous for M694V
      (61.4%). Although fever, abdominal pain, and arthritis were more commonly
      observed with the M694V mutation, chest pain was the most common symptom in R202Q
      carriers (n = 10, 32.3%). Proteinuria was observed in 42 (21.2%) patients,
      frequently accompanied by the M694V mutation (28.6%). The most common mutations
      in children with FMF in Turkey were M694V and R202Q. Recurrent abdominal pain and
      arthritis/arthralgia were commonly observed in patients with M694V and R202Q
      mutations. Moreover, chest pain was commonly seen with the R202Q mutation. Thus,
      R202Q might be a disease-causing mutation in FMF patients.

PMID- 30284127
TI  - Association Between SSR Molecular Markers and Chemical and Sensory Traits of
      Cacao Samples Using Multiple Regression Analysis.
AB  - The sensory properties of cacao beans are linked to the chemical composition of
      the seeds, and both characteristics are the partial results of its allelic
      composition. Therefore, it is useful to search for molecular markers associated
      with these traits. We perform multiple regression analysis to associate
      previously generated data of alleles generated with 12 SSR (of cultivated cacao
      trees) with data obtained from chemical and sensory characterization (of beans)
      of plants grown in the southern region from Mexico. When the association was
      significant, the mathematical models for predictive purposes were proposed. All
      phenotypic traits evaluated showed equations with setting values R2 > 0.5. All
      chemical characters tested have a significant association with at least two
      alleles (P < 0.05). In addition, the fat content was associated with six
      molecular markers (mTcCIR03209, mTcCIR12188, mTcCIR19286, mTcCIR07150,
      mTcCIR19310). The most common allele was mTcCIR12188, which was associated with
      the contents of eicosanoic acid, moisture, fat and total polyphenols content. The
      mTcCIR28362 allele is associated with sensory characters bitterness, musty odor,
      and roasted odor. These alleles could be useful as molecular markers of chemical
      and sensory characteristics of cacao samples.

PMID- 30284128
TI  - GLUT1 Variants for Predicting Prognosis After Surgery in Non-small Cell Lung
      Cancer.

PMID- 30284129
TI  - ASO Author Reflections: Even in Pancreatic Cancer, not all N Diseases are Created
      Equal.

PMID- 30284130
TI  - ASO Author Reflections: Moving Forward De-escalation of Axillary Surgery After
      Neoadjuvant Treatment in Breast Cancer.

PMID- 30284131
TI  - Survival Impact of Total Resected Lymph Nodes in Esophageal Cancer Patients With
      and Without Neoadjuvant Chemoradiation.
AB  - BACKGROUND: Current esophageal treatment guidelines suggest that, when more than
      15 lymph nodes are detected, dissection should be done as the minimum requirement
      for staging in esophageal squamous cell carcinoma (ESCC) patients undergoing
      esophagectomy without induction chemoradiotherapy (CRT). However, for neoadjuvant
      CRT, there is limited information. We sought to clarify the role of
      lymphadenectomy in ESCC patients with and without neoadjuvant CRT. PATIENTS AND
      METHODS: Data on 3156 ESCC patients receiving esophagectomy with (group 1, n =
      1399) and without (group 2, n = 1757) neoadjuvant CRT between 2008 and 2014 were
      collected from a national cancer registry in Taiwan. The impact of the resected
      lymph nodes on overall survival was assessed according to pathologic stages. A
      Cox regression model was used to identify prognostic factors for overall
      survival. RESULTS: Five-year overall survival rates were 35.6% for the entire
      group, 30.32% for group 1, and 39.55% for group 2 (p < 0.0001 for group 1 vs
      group 2). The best cutoff value was 21 lymph nodes in both group 1 and group 2.
      In group 1, the independent prognostic factors included age >= 54 years, clinical
      N status, y-pathologic T, y-pathologic N, y-pathologic stage, grade, location,
      margin status, esophagectomy (thoracoscopic vs open), and number of total
      resected lymph nodes (<= 21 vs > 21). For group 2, the independent prognostic
      factors were gender, clinical stage, pathologic T, pathologic N, tumor length,
      grade, and margin status. CONCLUSIONS: Extent of lymphadenectomy was associated
      with survival in patients with neoadjuvant CRT followed by esophagectomy. The
      optimum lymphadenectomy should be modulated by pathologic stage.

PMID- 30284132
TI  - The Role of Completion Lymph Node Dissection for Sentinel Lymph Node-Positive
      Melanoma.
AB  - PURPOSE AND METHODS: Completion lymph node dissection (CLND) for sentinel lymph
      node (SLN)-positive melanoma patients has been guideline-concordant standard of
      care since adoption of lymphatic mapping and SLN biopsy for the management of
      clinically node-negative melanoma patients more than 20 years ago. However, a
      trend for omission of CLND has been observed over the past decade, and we now
      have randomized, controlled clinical trial data to help guide treatment
      recommendations. Publication of these data prompted an American Society of
      Clinical Oncology-Society of Surgical Oncology 2018 clinical practice guideline
      update for these patients. RESULTS AND CONCLUSIONS: Systematic review of current
      evidence supports a selective, individualized approach to CLND for SLN-positive
      melanoma. For low-risk, low-volume micrometastatic disease, SLN biopsy may be
      both diagnostic and therapeutic, and close clinical follow-up with imaging or
      CLND are reasonable options for appropriately selected patients. For higher-risk
      patients, omission of CLND requires careful consideration of risks versus
      benefits, relevant histopathology, and individualized patient discussion. This
      should address patient comorbidities and life expectancy, the predicted
      likelihood of additional positive nodes, availability of imaging surveillance,
      likelihood of adherence to imaging and clinical follow-up, consequences of
      regional recurrence, and the prognostic value of complete nodal staging and its
      impact on adjuvant therapy recommendations or clinical trial participation. Data
      on long-term outcomes, cost, and patient-reported quality of life measures are
      not yet available.

PMID- 30284133
TI  - Delayed Bleeding After Colorectal Endoscopic Submucosal Dissection: When Is
      Emergency Colonoscopy Needed?
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment for
      early-colorectal cancer. Although delayed bleeding is a serious potential
      complication, there is no consensus on the optimal protocol to determine which
      cases require emergency colonoscopy. AIMS: This study aimed to assess the risk
      factors for delayed bleeding after ESD and evaluate the "watch and wait" strategy
      for delayed bleeding. The "watch and wait" strategy was used for delayed
      bleeding, unless the shock index was >= 1 and/or a moderate amount of
      hematochezia occurred more than five occurrences. METHODS: This study included
      404 patients who had undergone endoscopic resection for 439 lesions between April
      2012 and February 2018. Patients were classified into the bleeding group or the
      no-bleeding group to investigate the risk factors for delayed bleeding, and to
      assess the necessity of emergency colonoscopy. RESULTS: Twenty-seven patients
      into the bleeding group and 412 into the no-bleeding group were classified.
      However, no case required emergency colonoscopy for hemostasis under "watch and
      wait strategy." Multivariate analysis revealed the risk factors for bleeding were
      rectal lesion (OR 5.547, 95% CI 1.456-21.130; P = 0.012) and lesion size >= 40 mm
      (OR 3.967, 95% CI 1.003-15.696; P = 0.05). CONCLUSIONS: Risk factors for delayed
      bleeding are rectal lesions and lesion size >= 40 mm. This watch and wait
      strategy resulted in no requirements for emergency colonoscopy or blood
      transfusion, and no serious conditions caused by delayed bleeding.

PMID- 30284134
TI  - Pharmacological Treatment of Opioid-Induced Constipation Is Effective but Choice
      of Endpoints Affects the Therapeutic Gain.
AB  - BACKGROUND: Widespread opioid use has led to increase in opioid-related adverse
      effects like constipation. We examined the impact of study endpoints on reported
      treatment benefits. METHODS: Using MEDLINE, EMBASE, and ClinicalTrials.gov, we
      searched for randomized control trials targeting chronic opioid-induced
      constipation (OIC) and subjected them to meta-analysis. Data are given with 95%
      confidence intervals. RESULTS: Thirty trials met our inclusion criteria.
      Combining all dichotomous definitions of responders, active drugs were
      consistently more effective than placebo, with an odds ratio (OR): 2.30 [2.01
      2.63; 15 studies], independent of the underlying drug mechanism. The choice of
      endpoints significantly affected the therapeutic gain. When time from drug
      administration to defecation was used, the OR decreased from 4.74 [2.71-4.74] at
      6 h or less to 2.46 [1.80-3.30] at 24 h (P < 0.05). Using other response
      definitions, the relative benefit over placebo was 2.10 [1.77-2.50; 12 studies]
      for weekly bowel frequency, 2.03 [1.39-2.95; 9 studies] for symptom scores, 2.21
      [1.25-3.90; 4 studies] for global assessment scales, and 1.27 [0.79-2.03; 7
      studies] for rescue laxative use. CONCLUSION: While treatment of OIC with active
      drugs is more effective than placebo, the relative gain depends on the choice of
      endpoints. The commonly used time-dependent response definition is associated
      with the highest response rate but is of questionable relevance in a chronic
      disorder. The limited data do not clearly demonstrate a unique advantage of the
      peripherally restricted opioid antagonists, suggesting that treatment with often
      cheaper agents should be optimized before shifting to these novel expensive
      agents.

PMID- 30284135
TI  - Resveratrol Improves Recovery and Survival of Diet-Induced Obese Mice Undergoing
      Extended Major (80%) Hepatectomy.
AB  - INTRODUCTION: Loss of hepatic epidermal growth factor receptor (EGFR) expression
      is a cause for the increased perioperative risk for complications and death in
      patients with obesity and fatty liver undergoing liver resection. Herein, we set
      out to identify agents that might increase EGFR expression and improve recovery
      for patients with fatty liver undergoing resection. Using the diet-induced obese
      (DIO) mouse model of fatty liver, we examined resveratrol as a therapy to induce
      EGFR expression and improve outcomes following 80% partial hepatectomy (PH) in a
      murine model. METHODS: DIO mice were fed resveratrol or carrier control by
      gavage. EGFR expression and the response to major (80%) PH were examined.
      RESULTS: Based on an Illumina analysis, resveratrol was identified as increasing
      EGFR gene expression in A549 cells. Resveratrol was observed to also increase
      EGFR protein expression in A549 cells. DIO mice fed resveratrol by gavage (75
      mg/kg) demonstrated an increased EGFR expression without the identified hepatic
      toxicity. Resveratrol and control mice subjected to 80% PH, a model of high
      mortality hepatectomy in DIO mice, demonstrated macroscopically decreased fatty
      liver and fewer liver hemorrhagic petechiae. Resveratrol pretreatment ameliorated
      liver injury and accelerated regeneration of the hepatic remnant after 80% PH
      including decreasing serum ALT and bilirubin, while increasing hepatic PCNA
      expression. Resveratrol increased induction of p-STAT3 and p-AKT after 80%
      hepatectomy. Resveratrol pretreatment significantly improved survival rates in
      DIO mice undergoing extended 80% PH. CONCLUSIONS: Oral resveratrol restores EGFR
      expression in fatty liver. Resveratrol may be a promising protective agent in
      instances where extensive hepatic resection of fatty liver is required.

PMID- 30284136
TI  - Research Progress on the Relationship Between Acute Pancreatitis and Calcium
      Overload in Acinar Cells.
AB  - Acute pancreatitis is a human disease with multiple causes that leads to
      autodigestion of the pancreas. There is sufficient evidence to support the key
      role of sustained increase in cytosolic calcium concentrations in the early
      pathogenesis of the disease. To clarify the mechanism of maintaining calcium
      homeostasis in the cell and pathological processes caused by calcium overload
      would help to research directly targeted therapeutic agents. We will specifically
      review the following: intracellular calcium homeostasis and regulation, the
      occurrence of calcium overload in acinar cells, the role of calcium overload in
      the pathogenesis of AP, the treatment strategy proposed for calcium overload.

PMID- 30284137
TI  - Interrupted Time Experience in Autism Spectrum Disorder: Empirical Evidence from
      Content Analysis.
AB  - Although the experience of time is of central relevance for psychopathology,
      qualitative approaches to study the inner experience of time have been largely
      neglected in autism research. We present results from qualitative data acquired
      from 26 adults with high functioning autism spectrum disorder (ASD). Employing
      inductive content analysis we identified a distinct pattern of interrupted time
      experience in ASD. Individuals with ASD seemed to implement structured and
      routine behavior by future planning to guarantee that the present passed
      uninterrupted. We reason that the success of corresponding compensatory
      mechanisms determines the development of distress and noticeable symptoms.
      Considering recent theories on Bayesian perceptual inference we relate the
      syndrome of interrupted time experience to the putative neuronal mechanisms
      underlying time experience.

PMID- 30284138
TI  - Correlation of FFR-derived from CT and stress perfusion CMR with invasive FFR in
      intermediate-grade coronary artery stenosis.
AB  - Only one-third of intermediate-grade coronary artery stenosis (i.e. 40-70%
      diameter narrowing) causes myocardial ischemia, requiring most often additional
      invasive work-up with invasive fractional flow reserve (FFR). To evaluate the
      correlations between FFR estimates derived from computed tomography (FFRCT) and
      adenosine perfusion cardiac magnetic resonance (CMR) with invasive FFR in
      intermediate-grade stenosis. Thirty-seven patients (mean age 61 +/- 9 years; 25
      men) who underwent adenosine perfusion CMR, quantitative coronary angiography and
      FFR in the work-up for intermediate-grade stenoses (n = 39) diagnosed at coronary
      CT angiography were retrospectively evaluated. Blinded FFRCT analysis was
      computed on each intermediate-grade lesion and correlated to the FFR values. On
      adenosine CMR, subendocardial time-enhancement maximal upslopes, normalized by
      respective left ventricle cavity upslopes, were obtained distal to a coronary
      stenosis (RISK area) and in remote myocardium (REMOTE area). The perfusion was
      subsequently assessed without (uncorrected RISK) and after correction for remote
      perfusion (relative myocardial perfusion index = REMOTE/RISK ratio), and then
      correlated to the FFR values. Differences in correlations were tested with z
      statistics and considered statistically significant different at a p < 0.05
      level. The average FFR value was 0.85 +/- 0.10 (0.60-0.98 range), 28% (n = 11)
      was <= 0.80. FFR value correlated poorly with uncorrected RISK upslopes (r =
      0.151; p = 0.36), but equally strongly with FFRCT (r = 0.675; p < 0.001) and the
      relative myocardial perfusion index (r = - 0.63) (p < 0.001; z = 6.72) for
      assessment of lesion-specific ischemia. Both FFRCT and adenosine perfusion CMR
      strongly correlate with invasive FFR measurements for intermediate-grade
      stenosis. These preliminary findings pave the way for further studies evaluating
      non-invasively intermediate coronary stenosis in clinical practice.

PMID- 30284139
TI  - Predictors of Quality of Life in Montreal, Canada: A Longitudinal Study.
AB  - This study sought to assess factors associated with quality of life (QoL), and
      predictive of improvements in QoL over time, in a population-based cohort study.
      A 4-year longitudinal survey was administered to 2433 individuals at the study
      baseline; of these, 1828 individuals participated in Wave 2, and 1303
      participated in Wave 3. QoL was measured by the Satisfaction with Life Domains
      Scale. Thirty-two variables were correlated with baseline QoL and together
      explained 58.2% of the variance. Eleven variables were independent predictors of
      improvement in QoL over time. Among these variables, social support and
      stress/coping showed the strongest association with QoL, and neighbourhood
      characteristics had an additional influence. Multidimensional modelling of a
      broad spectrum of the factors related to QoL enabled situating mental health and
      well-being in an ecological system with attendant implications for public health
      and social policy intervention to facilitate improvement of QoL in the
      population.

PMID- 30284140
TI  - Natural products from anaerobes.
AB  - Natural product discovery in the microbial world has historically been biased
      toward aerobes. Recent in silico analysis demonstrates that genomes of anaerobes
      encode unexpected biosynthetic potential for natural products, however, chemical
      data on natural products from the anaerobic world are extremely limited. Here, we
      review the current body of work on natural products isolated from strictly
      anaerobic microbes, including recent genome mining efforts to discover
      polyketides and non-ribosomal peptides from anaerobes. These known natural
      products of anaerobes have demonstrated interesting molecular scaffolds,
      biosynthetic logic, and/or biological activities, making anaerobes a promising
      reservoir for future natural product discovery.

PMID- 30284141
TI  - Post-exposure distribution of selenium and aluminum ions and their effects on
      superoxide dismutase activity in mouse brain.
AB  - The study was conducted to determine how aluminum (Al) and selenium (Se) ions
      alone and in combination affect superoxide dismutase (SOD) activity and to
      evaluate the distribution of these elements in the blood and the brain of
      laboratory mice. SOD activity in mouse brain was evaluated after single-time
      (within 24 h) and repeated (over 14 days) intraperitoneal (IP) injections of
      SeO32-, Al3+, and (SeO32-+Al3+) solutions. The control mice received IP
      injections of the same volume of saline. Aluminum concentration in mouse blood
      increased both after single-time and repeated injections of AlCl3 and the
      combined (AlCl3 + Na2SeO3) solutions. The concentration of Se increased in blood
      after single-time and repeated injections of Na2SeO3 and the combined (AlCl3 +
      Na2SeO3) solutions. After the single-time injection of the experimental
      solutions, the concentrations of both Al and Se in mouse brain remained at
      baseline, but after repeated injections of (AlCl3 + Na2SeO3) solutions increased
      aluminum concentration. A single IP injection of Al did not change SOD activity
      in mouse brain, while a single injection of Se or the Se + Al mixture decreased
      it. After 14 days, IP injections of Al or Se alone did not affect SOD activity,
      while their combination decreased it. Our results showed that Se ions decreased
      SOD activity in mouse brain after both single-time and repeated IP injections of
      selenium-containing solutions. The study failed to show a direct or linear effect
      of increased Al or Se concentrations on SOD activity in mouse brain.

PMID- 30284142
TI  - In silico 'fishing' using known small regulatory RNA (sRNA) candidates as the
      decoy from Escherichia coli, Salmonella typhi and Salmonella typhimurium
      manifested 14 novel sRNA candidates in the orthologous region of Proteus
      mirabilis.
AB  - Proteus mirabilis, a gram-negative bacterium of the family Enterobacteriaceae, is
      a leading cause of urinary tract infection (UTI) with rapid development of multi
      drug resistance. Identification of small regulatory RNAs (sRNAs), which belongs
      to a class of RNAs that do not translate into a protein, could permit the
      comprehension of the regulatory roles this molecules play in mediating
      pathogenesis and multi-drug resistance of the organism. In this study,
      comparative sRNA analysis across three different members of Enterobacteriaceae
      (Escherichia coli, Salmonella typhi and Salmonella typhimurium) was carried out
      to identify the sRNA homologs in P. mirabilis. A total of 232 sRNA genes that
      were reported in E. coli, S. typhi and S. typhimurium were subjected to
      comparative analysis against P. mirabilis HI4320 genome. We report the detection
      of 14 sRNA candidates, conserved in the orthologous regions of P. mirabilis, that
      are not included in Rfam database. Northern-blot analysis was carried out for
      selected three sRNA candidates from the current investigation and three known
      sRNA from Rfam of P. mirabilis. The expression pattern of the six sRNA candidates
      shows that they are growth stage-dependant. To the best of our knowledge, this is
      the first report on the identification of sRNA candidates in P. mirabilis.

PMID- 30284144
TI  - Mosaicism diminishes the value of pre-implantation embryo biopsies for detecting
      CRISPR/Cas9 induced mutations in sheep.
AB  - The production of knock-out (KO) livestock models is both expensive and time
      consuming due to their long gestational interval and low number of offspring. One
      alternative to increase efficiency is performing a genetic screening to select
      pre-implantation embryos that have incorporated the desired mutation. Here we
      report the use of sheep embryo biopsies for detecting CRISPR/Cas9-induced
      mutations targeting the gene PDX1 prior to embryo transfer. PDX1 is a critical
      gene for pancreas development and the target gene required for the creation of
      pancreatogenesis-disabled sheep. We evaluated the viability of biopsied embryos
      in vitro and in vivo, and we determined the mutation efficiency using PCR
      combined with gel electrophoresis and digital droplet PCR (ddPCR). Next, we
      determined the presence of mosaicism in ~ 50% of the recovered fetuses employing
      a clonal sequencing methodology. While the use of biopsies did not compromise
      embryo viability, the presence of mosaicism diminished the diagnostic value of
      the technique. If mosaicism could be overcome, pre-implantation embryo biopsies
      for mutation screening represents a powerful approach that will streamline the
      creation of KO animals.

PMID- 30284143
TI  - AGXT2 and DDAH-1 genetic variants are highly correlated with serum ADMA and SDMA
      levels and with incidence of coronary artery disease in Egyptians.
AB  - Dimethylarginine aminodehydrolase (DDAH1) and alanine glyoxylate
      aminotransferase2 (AGXT2) are two enzymes that contribute in asymmetric
      dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) metabolism. Hence
      they affect production and bioavailability of eNOS-derived nitric oxide (NO) and
      consequently healthy blood vessels. The major aims of the current study were to
      investigate the association of genetic variants of AGXT2 rs37369, AGXT2
      rs16899974 and DDAH1 rs997251 SNPs with incidence of coronary artery disease
      (CAD) in Egyptians and to correlate these variants with the serum levels of ADMA
      and SDMA. The study included 150 subjects; 100 CAD patients and 50 healthy
      controls. Genotyping was performed by qPCR while the ADMA and SDMA concentrations
      were assayed by ELISA. Both serum ADMA and SDMA concentrations were significantly
      higher in CAD patients compared to controls (both p < 0.0001). Genotype
      distributions for all studied SNPs were significantly different between CAD
      patients and controls. Carriers of AGXT2 rs37369-T allele (CT + TT genotypes) and
      AGXT2 rs16899974-A allele (CA + AA genotypes) had 2.4- and 2.08-fold higher risk
      of having CAD than CC genotype in both SNPs (p = 0.0050 and 0.0192,
      respectively). DDAH1 rs997251 TC + CC genotypes were associated with 2.3-fold
      higher risk of CAD than TT genotype (p = 0.0063). Moreover, the AGXT2 rs37369 TT
      and AGXT2 rs16899974 AA genotypes were associated with the highest serum ADMA and
      SDMA while DDAH1 rs997251 CC genotype was associated with the highest ADMA. AGXT2
      rs37369-T, AGXT2 rs16899974-A, and DDAH1 rs997251-C alleles represent independent
      risk factors for CAD in the Egyptians.

PMID- 30284146
TI  - Pathogen-Specific Clinical Trials: A New Paradigm in Clinical Trials for
      Multidrug-Resistant Organisms.

PMID- 30284147
TI  - A Framework of Interprofessional Telebehavioral Health Competencies:
      Implementation and Challenges Moving Forward.
AB  - Interprofessional telebehavioral health (TBH) competencies have been developed to
      standardize training and improve the quality of TBH care. The seven identified
      interprofessional TBH competency domains and three levels of expertise (novice,
      proficient, and authority) are briefly described. More in depth descriptions and
      examples of several of the competency domains are presented to illustrate what
      the competencies look like in practice. Some of the challenges faced in using
      such a competency framework are discussed.

PMID- 30284148
TI  - Social Media and Networking Competencies for Psychiatric Education: Skills,
      Teaching Methods, and Implications.

PMID- 30284145
TI  - In vivo epigenome editing and transcriptional modulation using CRISPR technology.
AB  - The rapid advancement of CRISPR technology has enabled targeted epigenome editing
      and transcriptional modulation in the native chromatin context. However, only a
      few studies have reported the successful editing of the epigenome in adult
      animals in contrast to the rapidly growing number of in vivo genome editing over
      the past few years. In this review, we discuss the challenges facing in vivo
      epigenome editing and new strategies to overcome the huddles. The biggest
      challenge has been the difficulty in packaging dCas9 fusion proteins required for
      manipulation of epigenome into the adeno-associated virus (AAV) delivery vehicle.
      We review the strategies to address the AAV packaging issue, including small
      dCas9 orthologues, truncated dCas9 mutants, a split-dCas9 system, and potent
      truncated effector domains. We discuss the dCas9 conjugation strategies to
      recruit endogenous chromatin modifiers and remodelers to specific genomic loci,
      and recently developed methods to recruit multiple copies of the dCas9 fusion
      protein, or to simultaneous express multiple gRNAs for robust epigenome editing
      or synergistic transcriptional modulation. The use of Cre-inducible dCas9
      expressing mice or a genetic cross between dCas9- and sgRNA-expressing flies has
      also helped overcome the transgene delivery issue. We provide perspective on how
      a combination use of these strategies can facilitate in vivo epigenome editing
      and transcriptional modulation.

PMID- 30284150
TI  - Did we see it Coming? An Evaluation of the Swedish Early Awareness and Alert
      System.
AB  - BACKGROUND: Early awareness and alert systems have been established in many
      countries but evidence on their ability to accurately prioritize new medicines
      (for early assessment) is limited. OBJECTIVE: The purpose of this study was to
      assess whether the Swedish Early Awareness and Alert System identified and
      prioritized (i.e., produced early assessment reports for) new medicines that
      would go on to have substantial economic impact. METHODS: We adapted a study
      design commonly used in the assessment of diagnostic test accuracy. The
      prioritization made by the Swedish Early Awareness and Alert System prior to
      marketing authorization comprised the index test and the national drug sales data
      in the second year post-authorization served as the reference standard. All
      initial marketing authorization applications for medicinal products processed by
      the European Medicines Agency between 2010 and 2015 (study population) were
      classified using the index test and the reference standard. RESULTS: Two hundred
      and fifty-three new medicinal products processed by the European Medicines Agency
      comprised the study population. Of these, 71 were prioritized by the Swedish
      Early Awareness and Alert System and 21 were classified as having substantial
      economic impact. The sensitivity and positive predictive value were 76.2% and
      22.5%, respectively. Subgroup analyses showed that the accuracy of
      prioritization, in terms of sensitivity, was 100% for
      antineoplastic/immunomodulating agents. CONCLUSIONS: The Swedish Early Awareness
      and Alert System identified all new medicines that would go on to have
      substantial economic impact and prioritized most of these medicines. Our findings
      provide reassurance to decision makers who rely on the outputs of the Swedish
      Early Awareness and Alert System to keep informed about new medicines. Moreover,
      this study also provides valuable insights to stakeholders willing to establish
      or evaluate their own early awareness and alert activities and systems.

PMID- 30284149
TI  - Inhibition of the ubiquitination of HSF1 by FBXW7 protects the intestine against
      ischemia-reperfusion injury.
AB  - Epithelial apoptosis is an important factor in intestinal ischemia-reperfusion
      (I/R) injury. Heat shock factor 1 (HSF1) is a classical stress response factor
      that directly regulates the transcription of heat shock proteins (HSPs) under
      stress conditions. Although HSPs are involved in protecting the intestine against
      I/R, the mechanism whereby HSF1 is regulated in I/R is poorly understood. Here,
      we show that the ubiquitin ligase FBXW7 targets HSF1 for ubiquitination and
      degradation in intestinal I/R. In this study, we found that FBXW7 expression was
      upregulated at the transcriptional level in intestinal mucosae subjected to I/R.
      In Caco-2 and IEC-6 cells subjected to hypoxia/reoxygenation (H/R), a high FBXW7
      level led to excessive HSF1 ubiquitination and degradation. FBXW7 knockdown
      attenuated HSF1 ubiquitination and downregulation and accelerated HSPB1 and HSP70
      expression. In addition, FBXW7 deletion alleviated the apoptosis of intestinal
      epithelial cells, as evidenced by decreased activation of caspase-3 and caspase
      9. The results suggest that FBXW7 suppression protects against intestinal I/R, at
      least partly through the HSF1/HSP pathway. These findings indicate that FBXW7 may
      be a potential therapeutic target for inhibiting intestinal mucosa apoptosis
      during intestinal I/R.

PMID- 30284151
TI  - Current Strategies and Future Outlook for Managing the Neotropical Tomato Pest
      Tuta absoluta (Meyrick) in the Mediterranean Basin.
AB  - The invasion of new regions by exotic pests has been more than ever a critical
      issue that warrants coordinated international actions to manage established
      populations and prevent further spreading. Invasive insects can undermine the
      ecological equilibrium of both natural and agricultural ecosystems. Moreover,
      increasing temperatures due to climatic change exacerbate this problem by
      allowing pests to further reach regions previously considered unsuitable. The
      tomato pinworm Tuta absoluta (Meyrick) (Lepidoptera) is an exotic pest native to
      Peru that has spread beyond Neotropical America. In Europe, its occurrence was
      reported in Spain in 2006, and thereafter, it has spread throughout the
      Mediterranean Basin and further into Africa and part of Asia. While T. absoluta
      can cause losses to tomato production all over the globe, the differences in each
      invaded region (e.g., climate, vegetation) may affect its population dynamics
      and, consequently, management protocols. Therefore, the main intent of this forum
      paper is to explore how European growers and researchers are dealing with T.
      absoluta in the Mediterranean area. As for many other invasive pests, the best
      approach has been the adoption of integrated pest management (IPM). Specifically,
      the integration of biological control agents (e.g., mirid predators and egg
      parasitoids), microbial insecticides (i.e., Bacillus thuringiensis), selective
      chemical insecticides, and sex pheromone-based control has proven adequate,
      especially in tomato greenhouses. Nonetheless, some of the challenges ahead
      include the development of resistant tomato cultivars, the management of wild
      vegetation and companion plants to optimize the conservation of natural enemies
      and their effectiveness at the crop level, the management of insecticide
      resistance, and the improvement of sex pheromone-based tactics.

PMID- 30284152
TI  - Silver in the meat and organs of broiler chickens in case of using colloidal
      silver as an alternative to antibiotics.
AB  - The search for new antibacterial products, the mechanisms of action of which
      differ from conventional antibiotics is a current a topical issue. The objective
      of our research is to identify the presence of silver in meat and organs of
      broiler chicks that had been given colloidal silver. The results show that the
      broiler chick meat contains silver in quantities safe for humans regardless of
      the use of colloidal silver. Comparison of meat analysis results in experimental
      and control groups indicate that the ratio of parameters distribution variance
      for all birds to the mean variance by group for each measured no statistical
      differences in the chemical composition of bird's meat of experimental and
      control groups. The analysis also confirmed the existing difference in chemical
      composition of leg muscle meat and chest muscle meat (P < 0.05), whereas leg
      muscle contains more fat (6.81% vs. 2.85%) and less protein (20.25% vs. 22.81%).

PMID- 30284153
TI  - Detecting drug-resistant tuberculosis in chest radiographs.
AB  - PURPOSE: Tuberculosis is a major global health threat claiming millions of lives
      each year. While the total number of tuberculosis cases has been decreasing over
      the last years, the rise of drug-resistant tuberculosis has reduced the chance of
      controlling the disease. The purpose is to implement a timely diagnosis of drug
      resistant tuberculosis, which is essential to administering adequate treatment
      regimens and stopping the further transmission of drug-resistant tuberculosis.
      METHODS: A main tool for diagnosing tuberculosis is the conventional chest X-ray.
      We are investigating the possibility of discriminating automatically between drug
      resistant and drug-sensitive tuberculosis in chest X-rays by means of image
      analysis and machine learning methods. RESULTS: For discriminating between drug
      sensitive and drug-resistant tuberculosis, we achieve an area under the receiver
      operating characteristic curve (AUC) of up to 66%, using an artificial neural
      network in combination with a set of shape and texture features. We did not
      observe any significant difference in the results when including follow-up X-rays
      for each patient. CONCLUSION: Our results suggest that a chest X-ray contains
      information about the likelihood of a drug-resistant tuberculosis infection,
      which can be exploited computationally. We therefore suggest to repeat the
      experiments of our pilot study on a larger set of chest X-rays.

PMID- 30284154
TI  - Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis-1 with
      Everolimus: A Phase II, Open-Label, Single-Arm Trial.
AB  - BACKGROUND: Cutaneous neurofibromas cause disfigurement and discomfort in
      individuals with neurofibromatosis type 1 (NF-1). METHODS: The primary objective
      of this phase II, open-label, single-arm trial was to assess whether orally
      administered everolimus reduced the surface volume of cutaneous neurofibromas in
      patients with NF-1. RESULTS: Of 22 patients who took the study drug, 17 completed
      the trial; 5 patients withdrew due to adverse events. Sixteen patients had
      photographs of sufficient quality for assessment of the primary outcome. A
      significant reduction in lesion surface volume, defined as an end of trial volume
      > 2 standard errors (SE) less than baseline volume, was observed for 4/31 lesions
      (13%) from 3/16 patients (19%). Additionally, a statistically significant
      absolute change in average height for paired lesions was observed (p = 0.048).
      Although not a prespecified outcome measure, a dramatic reduction in the size of
      3 large plexiform neurofibromas with a cutaneous component was also noted and
      documented by measurement of maximum circumference or magnetic resonance imaging
      based volumetric analysis. Adverse events were common in this trial, but no
      serious adverse events occurred. CONCLUSIONS: Although this was a small,
      exploratory trial that was not powered for significance, the reduction in surface
      volume observed in this study is noteworthy assuming that the natural course for
      untreated lesions is to maintain or increase in volume. Future studies are needed
      with larger study populations that incorporate longer durations of treatment and
      better standardization of volumetric measurements. Trial Registration
      ClinicalTrials.gov Identifier: NCT02332902.

PMID- 30284155
TI  - Histogram Analysis Parameters Derived from Conventional T1- and T2-Weighted
      Images Can Predict Different Histopathological Features Including Expression of
      Ki67, EGFR, VEGF, HIF-1alpha, and p53 and Cell Count in Head and Neck Squamous
      Cell Carcinoma.
AB  - PURPOSE: To analyze associations between histogram analysis parameters derived
      from conventional magnetic resonance imaging (MRI) and different
      histopathological features in head and neck squamous cell carcinoma (HNSCC).
      PROCEDURES: Thirty-four patients with histologically proven primary HNSCC were
      prospectively acquired. Histogram analysis was derived from pre-contrast T1
      weighted (T1w) and T2-weighted (T2w) images. In all cases, expression of HIF
      1alpha, VEGF, EGFR, p53, Ki67, and p16 as well as tumor cell count was analyzed.
      RESULTS: In the overall sample, inverse correlation between entropy derived from
      T1w images and p53 expression (p = - 0.458, P = 0.01) was found. Furthermore, p10
      derived from T1w images correlated with VEGF expression (p = 0.371, P = 0.04). In
      the p16-positive tumors, VEGF expression correlated with several parameters
      derived from T1w images: mean (p = 0.481, P = 0.032), p10 (p = 0.489, P = 0.029),
      p25 (p = 0.475, P = 0.034), median (p = 0.468, P = 0.037), and mode (p = 0.492, P
      = 0.028). Several T2w parameters were associated with p53 expression: mean (p =
      0.569, P = 0.007), p25 (p = 0.508, P = 0.019), p75 (p = 0.479, P = 0.028), median
      (p = 0.555, P = 0.009), and mode (p = 0.468, P = 0.033). Kurtosis derived from
      T2w images correlated with cell count (p = 0.534, P = 0.013). In p16-negative
      carcinomas, T2w parameters correlated with p53 expression: max (p = 0.736, P =
      0.015), p90 (p = 0.687, P = 0.028), and standard deviation (p = 0.760, P =
      0.011). T2w p10 (p = - 0.709, P = 0.022) and T2w p25 (p = - 0.733, P = 0.016)
      correlated also with HIF-1alpha expression. CONCLUSIONS: Multiple associations
      between histogram parameters derived from T1w and T2w images and clinically
      relevant histopathological features were found in HNSCC. Therefore, imaging
      parameters can be also used as surrogate markers for tumor cellularity,
      proliferation, and vascularization in HNSCC. The identified correlations differed
      significantly between p16-positive and p16-negative cancers.

PMID- 30284156
TI  - Reduction in Cannabis Use and Functional Status in Physical Health, Mental
      Health, and Cognition.
AB  - Treatment for substance use disorders has traditionally been abstinence-oriented,
      but evaluating the merits of low-level cannabis use as potential treatment
      endpoint may identify benefits that are clinically relevant for treatment-seeking
      individuals who do not attain abstinence. This study explores if reduction in
      cannabis use to a lower level of use is related to improved physical health,
      mental health, and perceived cognitive functions. Study participants with a
      history of problematic cannabis use (n = 111) completed assessments. Regression
      models were used to explore the relationship between past 30-day cannabis use
      levels (abstinent [57%], low use [22%] defined as less than or equal to 3 days
      per week, and heavy use [22%] defined as 4 or more days of use per week) and
      functional status in physical health, mental health, and cognition. Compared to
      heavy users, both abstinent and low-use individuals were similarly associated
      with better global health, appetite, and depression outcomes. Abstinent users
      also reported improved sleep, anxiety, and self-reported cognitive functioning
      relative to heavy users. Thus, reduction in cannabis use to lower levels is
      associated with beneficial outcomes important to health and other areas of
      functioning in individuals with problematic cannabis use.

PMID- 30284158
TI  - Prevention Research with Indigenous Communities to Expedite Dissemination and
      Implementation Efforts.
AB  - Effectively translating evidence-based interventions into clinic and community
      settings is an increasing priority for health researchers. The successful
      dissemination and implementation (D&I) of interventions found efficacious ensures
      that major health funders such as the National Institutes of Health can
      demonstrate a return on investment in biomedical and behavioral research and that
      all populations receive maximum benefit from scientific discoveries. However, the
      products of research efficacy trials, the evidence-based interventions, are
      rarely designed with D&I in mind, rendering these interventions fundamentally
      misaligned with real-world settings. Further, while some evidence-based
      interventions have been successfully adapted for implementation in indigenous
      communities, few such examples have been published. Literature regarding the
      adoption and implementation of evidence-based interventions in indigenous
      communities is scarce, and the feasibility of scaling up successful interventions
      is poorly understood, potentially widening health disparities. The Intervention
      Research to Improve Native American Health (IRINAH) partners are generating
      efficacy data on community-responsive and engaged interventions that are also
      designed to facilitate D&I efforts, reducing the time between research to
      practice to benefit indigenous communities, should these interventions prove
      effective. In this manuscript, we provide an overview and key challenges of D&I
      science with indigenous communities. We then use IRINAH case studies to highlight
      strategies that IRINAH partners are using to plan for the scale-up and
      implementation of the studies. We conclude with recommendations to inform the
      next phase of IRINAH research efforts.

PMID- 30284159
TI  - Using Zoning as a Public Health Tool to Reduce Oversaturation of Alcohol Outlets:
      an Examination of the Effects of the New "300 Foot Rule" on Packaged Goods Stores
      in a Mid-Atlantic City.
AB  - The oversaturation of alcohol outlets can have disastrous public health
      consequences. The goal of this study was to evaluate the potential impact of new
      zoning legislation, TransForm Baltimore on locations of alcohol outlets. More
      specifically, the study sought to determine the effect of the new zoning code on
      the potential redistribution of alcohol outlets and also provide empirical
      support for the need to actively monitor redistribution of outlets to avoid
      further inequitable oversaturation in disadvantaged neighborhoods. Data on off
      premise alcohol outlets (e.g., packaged goods stores) were obtained from the
      Board of Liquor License Commissioners for Baltimore City. The alcohol outlets
      were geocoded and assigned to zoning parcels. Churches and schools were also
      geocoded. The alcohol outlets were also assigned to census tracts to calculate
      socioeconomic statuses. One hundred seventy-two of the 263 off-premise packaged
      goods stores (PGS) were in violation of the new zoning law. TransForm will reduce
      the land parcels available to alcohol outlets by 27.2%. Areas containing non
      conforming PGS were more likely to have a higher percentage of Black residents,
      single parent-families, unemployment, household poverty, and vacancy compared to
      Baltimore City averages and areas without non-conforming PGS. Planning
      enforcement efforts need to accompany related laws to prevent/reduce
      overconcentration of PGS in disadvantaged neighborhoods.

PMID- 30284161
TI  - Co-contamination of antibiotics and metals in peri-urban agricultural soils and
      source identification.
AB  - To identify the dominant sources of contamination in peri-urban land, this study
      investigated the concentrations and distributions of antibiotics and metals in
      agricultural soil of this area. An index of landscape development intensity (LDI)
      was used to characterize the distribution of human disturbance-related land use.
      The results showed that total antibiotic concentration in the soil reached 395.55
      MUg/kg and that chlortetracycline was the predominant antibiotic compound, with a
      relatively high mean concentration of 30.62 MUg/kg. In soils, the mean
      concentrations of Cu, Zn, and Pb were 38.41, 127.88, and 56.61 mg/kg and those of
      Al, Fe, and K were 83.73, 24.17, and 23.42 g/kg, respectively. A redundancy
      analysis showed that the landscape pattern in a 300-m buffer zone can well
      explain the variation in the concentrations of antibiotics and metals (24%, p <
      0.05). The LDI in the 300-m buffer zone significantly correlated with the
      concentrations of total antibiotics and total amounts of Cu and Zn in the soil,
      suggesting that the risk of soil contamination increases with the intensity of
      anthropogenic activities. A structural equation modeling analysis indicated that
      Al, Cu, and Zn could significantly aggravate accumulation of tetracycline
      antibiotics in the soil, whereas there were only significantly direct paths from
      Cu to ciprofloxacin and norfloxacin. Overall, the results showed that aggravated
      co-contamination of antibiotics and metals occurs in agricultural soil under
      intensive human disturbance.

PMID- 30284162
TI  - Occurrence and risk assessment of heavy metals in water, sediment, and fish from
      Dongting Lake, China.
AB  - In this study, 15 representative surface waters and sediments and seven typical
      fish were collected during the wet season in 2016 to explore the occurrence,
      chemical fractionation, and ecological risk of heavy metals (Cu, Zn, Pb, Cd, Cr,
      Hg, As, and Ni) in aquatic ecosystems of Dongting Lake in China. In surface
      water, the concentrations of all elements were lower than the third grade of the
      surface water quality standards (GB3838-2002). The highest concentrations of Zn,
      Pb, Cd, Ni, and Cu were found in the outlet of Dongting Lake, whereas As and Cr
      were highest in the Xiangjiang River Delta area. In surface sediments, the
      concentration decreased in the order of Zn > Cr > Pb > Cu > Ni > As>Cd > Hg; the
      highest concentration of all elements, except for Hg, was located in the
      Xiangjiang River Delta area; for chemical fractionation, Cr, Hg, Zn, As, Ni, and
      Cu were mainly residual fractionation; and Pb and Cd were mainly in a reducible
      state and fraction soluble in acid, respectively. In fish muscle, the
      concentrations of all elements were lower than relevant standards; the highest
      concentration appeared in fish living in the middle-lower and demersal layers. As
      for the feeding habits of fish, the average concentration decreased in the order
      of carnivorous > omnivorous > herbivorous fish. The potential ecological risk and
      the ratio of secondary phase to primary phase assessment showed that Cd and Hg
      had the highest ecological risk and that Cd and Pb had a high risk of secondary
      release. A health risk assessment showed that drinking water and fish for
      consumption in urban and rural areas around Dongting Lake were in the acceptable
      level.

PMID- 30284160
TI  - Phytohormones enhanced drought tolerance in plants: a coping strategy.
AB  - Drought stress is a severe environmental constraint among the emerging problems.
      Plants are highly vulnerable to drought stress and a severe decrease in yield was
      recorded in the last few decades. So, it is highly desirable to understand the
      mechanism of drought tolerance in plants and consequently enhance the tolerance
      against drought stress. Phytohormones are known to play vital roles in regulating
      various phenomenons in plants to acclimatize to varying drought environment.
      Abscisic acid (ABA) is considered the main hormone which intensifies drought
      tolerance in plants through various morpho-physiological and molecular processes
      including stomata regulation, root development, and initiation of ABA-dependent
      pathway. In addition, jasmonic acid (JA), salicylic acid (SA) ethylene (ET),
      auxins (IAA), gibberellins (GAs), cytokinins (CKs), and brassinosteroids (BRs)
      are also very important phytohormones to congregate the challenges of drought
      stress. However, these hormones are usually cross talk with each other to
      increase the survival of plants in drought conditions. On the other hand, the
      transgenic approach is currently the most accepted technique to engineer the
      genes responsible for the synthesis of phytohormones in drought stress response.
      Our present review highlights the regulatory circuits of phytohormones in drought
      tolerance mechanism.

PMID- 30284163
TI  - Biochar amendment immobilizes arsenic in farmland and reduces its
      bioavailability.
AB  - This study aimed to determine effects of biochar derived from wheat straw at 500 
      degrees C on arsenic immobilization in a soil-Brassica campestris L system. When
      the soils amended with 4% modified biochar (MBC), 0.5% Fe grit as zero-valent
      iron (ZVI), 0.5% Fe grit + 4% MBC (ZMBC), 0.5% ZVI + 4% biochar (ZBC), 4% biochar
      (BC), and control (without amendments), it confirmed that available arsenic
      concentration in soils occurred in the following order: ZMBC < MBC < ZVI < ZBC <
      Control < BC. Water-soluble As (WSAs) was reduced by 89.74% and 92.30% in MBC-
      and ZMBC-amended soils, respectively, compared to the control. When MBC applied
      into soil, As uptake of shoot and root decreased by 44.55% and 45.40%,
      respectively, and ZMBC resulted in 74.92% and 71.80% reduction in shoot and root
      As of Brassica campestris L. Immobilization effect of As in ZBC was also observed
      though BC elevated plant As uptake significantly. The immobilization effect of
      MBC was mainly attributed to Fe2O3 impregnation illustrated by x-ray diffraction
      (XRD) and scanning electron microscopy (SEM) images through sorption,
      precipitation, and coprecipitation. Such Fe containing complexes might impede As
      translocation from root to shoot and subsequently reduce As accumulation in the
      plant with modified biochar amendment.

PMID- 30284164
TI  - Antimicrobial and antifouling properties of versatile PPSU/carboxylated GO
      nanocomposite membrane against Gram-positive and Gram-negative bacteria and
      protein.
AB  - Biofouling is a serious issue in membrane-based water and wastewater treatment as
      it critically compromises the efficacy of the water treatment processes. This
      investigation demonstrates the antimicrobial and antifouling properties of a
      nanocomposite membrane system composed of carboxyl-functionalized graphene oxide
      (COOH-GO) and polyphenylsulfone (PPSU). The PPSU/COOH-GO nanocomposite membrane
      exhibited excellent antimicrobial properties, achieving maximum bacteriostasis
      rates of 74.2% and 81.1% against the representative Gram-negative bacteria
      (Escherichia coli and Pseudomonas aeruginosa, respectively) and 41.9% against the
      representative Gram-positive bacterium (Staphylococcus aureus). The PPSU/COOH-GO
      nanocomposite membrane inhibited the attachment, colonization, and the biofilm
      formation of three species. Antifouling was assessed through filtration
      experiments using a model foulant bovine serum albumin (BSA). The fouling
      mechanisms were investigated by Hermia's models (complete blocking, intermediate
      blocking, standard blocking, and cake formation), and the analysis involved
      fitting the volumetric flux decline experimental data to models. The fouling
      study revealed a less irreversible fouling and increased flux recovery ratio for
      the PPSU/COOH-GO nanocomposite membrane. Complete blocking of pores and cake
      formation were the major fouling mechanisms for the membrane.

PMID- 30284165
TI  - Effective industrial regeneration of arsenic poisoning waste selective catalytic
      reduction catalyst: contaminants removal and activity recovery.
AB  - In this work, an environmental friendly industrial regeneration approach has been
      proposed to remove the surface poisoning and recover the catalytic activity of
      waste V2O5-WO3/TiO2 catalyst. Alkaline treatment and acid wash are combined for
      the waste catalyst regeneration process, which is applied for the arsenic and
      alkali metal removal, respectively. The crystal structure was well maintained as
      anatase phase and the surface area was increased during the regeneration, which
      is favorable for the following active component addition step and regenerated
      process. The XPS results illustrated that the surface contaminants (arsenic and
      sodium) were removed and V(IV) was loaded on the regenerated catalyst. Based on
      the deNOx evaluations, the catalytic activity of the regenerated sample is
      increased to the level of commercial fresh catalyst. The present industrial
      regeneration process provides a promising method for the comprehensive recovery
      of waste catalyst and further understanding in the field of secondary resource
      recycle.

PMID- 30284166
TI  - Enhanced photocatalytic activity of BiVO4 powders synthesized in presence of EDTA
      for the decolorization of rhodamine B from aqueous solution.
AB  - Bismuth vanadate (BiVO4) powders were successfully synthesized in presence of
      EDTA via microwave irradiation and used as photocatalysts in the oxidation
      reaction of rhodamine B (rhB) under visible light. Different concentrations of
      EDTA (0.5 to 10%) to chelate Bi3+ ions were employed on the BiVO4 synthesis.
      Under the presence of EDTA, a monoclinic crystalline structure was obtained,
      whereas a mixture of monoclinic and tetragonal phases was observed in the absence
      of EDTA. In addition, the use of different EDTA concentrations promoted the
      formation the different shapes of particles. The BiVO4 sample synthesized with
      low concentration of EDTA (0.5%) exhibited about 85% of rhB decolorization in 300
      min at pH 7.5. Therefore, this high efficiency can be attributed to a combination
      of intrinsic properties such as the morphology type and monoclinic structure of
      BiVO4 particles.

PMID- 30284167
TI  - Minimal-flow ECCO2R in patients needing CRRT does not facilitate lung-protective
      ventilation.
AB  - Extracorporeal CO2 removal (ECCO2R) is intended to facilitate lung protective
      ventilation in patients with hypercarbia. The combination of continuous renal
      replacement therapy (CRRT) and minimal-flow ECCO2R offers a promising concept for
      patients in need of both. We hypothecated that this system is able to remove
      enough CO2 to facilitate lung protective ventilation in mechanically ventilated
      patients. In 11 ventilated patients with acute renal failure who received either
      pre- or postdilution CRRT, minimal-flow ECCO2R was added to the circuit. During 6
      h of combined therapy, CO2 removal and its effect on facilitation of lung
      protective mechanical ventilation were assessed. Ventilatory settings were kept
      in assisted or pressure-controlled mode allowing spontaneous breathing. With
      minimal-flow ECCO2R significant decreases in minute ventilation, tidal volume and
      paCO2 were found after one and three but not after 6 h of therapy. Nevertheless,
      no significant reduction in applied force was found at any time during combined
      therapy. CO2 removal was 20.73 ml CO2/min and comparable between pre- and
      postdilution CRRT. Minimal-flow ECCO2R in combination with CRRT is sufficient to
      reduce surrogates for lung-protective mechanical ventilation but was not
      sufficient to significantly reduce force applied to the lung. Causative might be
      the absolute amount of CO2 removal of only about 10% of resting CO2 production in
      an adult as we found. The benefit of applying minimal flow ECCO2R in an
      uncontrolled setting of mechanical ventilation might be limited.

PMID- 30284168
TI  - Rolipram plus Sivelestat inhibits bone marrow-derived leukocytic lung recruitment
      after cardiopulmonary bypass in a primate model.
AB  - Cardiopulmonary bypass (CPB) recovery is complicated by lung inflammation from
      bone marrow (BM)-derived polymorphonuclear leukocytes (PMNs) and monocytes (MO).
      Although Sivelestat reduces inflammatory mediators and Rolipram inhibits PMN and
      MO activation, any kinetic effects to improve CPB recovery in vivo are unknown.
      We hypothesized that intraoperative co-administration of these compounds would
      reduce CPB-induced lung inflammation through downregulation of PMN and MO
      recruitment. A 2-h CPB was surgically established in cynomolgus monkeys (n = 13),
      and BM leukocyte release and lung recruitment were monitored postoperatively by
      flow cytometry with 5'-bromo-2'-deoxyuridine (BrdU) and cytokine ELISA. Either
      Sivelestat, Sivelestat plus Rolipram, or saline (control) was administered
      intraoperatively and both peripheral and perfusion sampling courses revealed BrdU
      labeled cells representative of activated leukocyte infiltration. Levels of
      cytokines CD11b and CD18 were leukocytic activation markers. Sivelestat plus
      Rolipram attenuated increases in CPB-associated circulating band cells, prolonged
      BM-transit time (PMN: 121.0 +/- 3.7 to 96.2 +/- 4.3 h [control], p = 0.012; MO:
      84.4 +/- 4.1 to 61.4 +/- 3.0 h [control], p = 0.003), and reduced their alveolar
      appearance. CD11b-mediated PMN and MO changes during CPB and the post-surgical
      increases of Interleukin (IL)-6 and IL-8 in the bronchoalveolar lavage fluid were
      suppressed. Sivelestat alone increased PMN transit time to 115.8 +/- 6.6 h, but
      monocytes were unaffected. Therefore, Rolipram has additive inhibitory effects
      with Sivelestat on the CPB-induced activation and release of BM-derived PMNs and
      MO and their recruitment to the lungs. Co-administration of these compounds
      could, therefore, hold value for preventing CPB-induced lung injury.

PMID- 30284169
TI  - Chronically Happy.

PMID- 30284170
TI  - Gout In Extremis: Massive Soft Tissue Tophaceous Deposits.

PMID- 30284171
TI  - Risk Factors for Diagnosis of Colorectal Cancer at a Late Stage: a Population
      Based Study.
AB  - BACKGROUND: Late-stage colorectal cancer (CRC) is associated with significantly
      less effective treatment and poorer survival than early-stage colorectal cancer.
      OBJECTIVE: Identify and assess patient characteristics, demographic factors, and
      lifestyle factors that are associated with late-stage colorectal cancer at
      diagnosis. APPROACH: We linked two longstanding statewide, population-based
      registry databases: the New Hampshire Colonoscopy Registry and the New Hampshire
      State Cancer Registry, to assess the associations between patient characteristics
      and late-stage CRC diagnoses. The State Cancer Registry provided information on
      cancer stage and the Colonoscopy Registry provided detailed information on
      patient characteristics and lifestyle factors, allowing these factors to be
      analyzed in relation to colorectal cancer stage. KEY RESULTS: The risk of late
      stage CRC diagnosis was highest among those diagnosed at a young age (< 50 years
      old) (OR 1.81, 95% CI 1.27-2.58). Those with Medicaid were also at increased
      risk, particularly < 65 years of age (OR 2.32, 95% CI 1.05-5.26). A family or
      personal history of polyps and/or CRC was associated with early stage at
      diagnosis (p = 0.014). CONCLUSIONS: Public health outreach and screening efforts
      should focused on patients at risk of late-stage CRC to encourage earlier
      diagnosis and prevention. Underserved patients have a lower rate of CRC screening
      and an increased risk of late-stage CRC, emphasizing the critical need to reach
      these populations. Further investigation of susceptibility characteristics and
      the effectiveness of non-invasive early screening techniques is warranted to
      address the late-stage CRC diagnoses in young individuals.

PMID- 30284172
TI  - Quality Improvement and Personalization for Statins: the QUIPS Quality
      Improvement Randomized Trial of Veterans' Primary Care Statin Use.
AB  - BACKGROUND: Implementation of new practice guidelines for statin use was very
      poor. OBJECTIVE: To test a multi-component quality improvement intervention to
      encourage use of new guidelines for statin use. DESIGN: Cluster-randomized, usual
      care controlled trial. PARTICIPANTS: The study population was primary care visits
      for patients who were recommended statins by the 2013 guidelines, but were not
      receiving them. We excluded patients who were over 75 years old, or had an ICD9
      or ICD10 code for end-stage renal disease, muscle pain, pregnancy, or in vitro
      fertilization in the 2 years prior to the study visit. INTERVENTIONS: A novel
      quality improvement intervention consisting of a personalized decision support
      tool, an educational program, a performance measure, and an audit and feedback
      system. Randomization was at the level of the primary care team. MAIN MEASURES:
      Our primary outcome was prescription of a medium- or high-strength statin. We
      studied how receiving the intervention changed care during the quality
      improvement intervention compared to before it and if that change continued after
      the intervention. KEY RESULTS: Among 3787 visits to 43 primary care providers,
      being in the intervention arm tripled the odds of patients being prescribed an
      appropriate statin (OR 3.0, 95% CI 1.8-4.9), though the effect resolved after the
      personalized decision support ended (OR 1.7, 95% CI 0.99-2.77). CONCLUSIONS: A
      simple, personalized quality improvement intervention is promising for enabling
      the adoption of new guidelines. CLINICALTRIALS. GOV IDENTIFIER: NCT02820870.

PMID- 30284174
TI  - Preferences for Physician Roles in Follow-up Care During Survivorship: Do
      Patients, Primary Care Providers, and Oncologists Agree?

PMID- 30284173
TI  - Telehealth Interventions Designed for Women: an Evidence Map.
AB  - BACKGROUND: Telehealth employs technology to connect patients to the right
      healthcare resources at the right time. Women are high utilizers of healthcare
      with gender-specific health issues that may benefit from the convenience and
      personalization of telehealth. Thus, we produced an evidence map describing the
      quantity, distribution, and characteristics of evidence assessing the
      effectiveness of telehealth services designed for women. METHODS: We searched
      MEDLINE(r) (via PubMed(r)) and Embase(r) from inception through March 20, 2018.
      We screened systematic reviews (SRs), randomized trials, and quasi-experimental
      studies using predetermined eligibility criteria. Articles meeting inclusion
      criteria were identified for data abstraction. To assess emerging trends, we also
      conducted a targeted search of ClinicalTrials.gov . RESULTS: Two hundred thirty
      four primary studies and three SRs were eligible for abstraction. We grouped
      studies into focused areas of research: maternal health (n = 96), prevention (n =
      46), disease management (n = 63), family planning (n = 9), high-risk breast
      cancer assessment (n = 10), intimate partner violence (n = 7), and mental health
      (n = 3). Most interventions focused on phone as the primary telehealth modality
      and featured healthcare team-to-patient communication and were limited in
      duration (e.g., < 12 weeks). Few interventions were conducted with older women
      (>= 60 years) or in racially/ethnically diverse populations. There are few SRs in
      this area and limited evidence regarding newer telehealth modalities such as
      mobile-based applications or short message service/texting. Targeted search of
      clinical.trials.gov yielded 73 ongoing studies that show a shift in the use of
      non-telephone modalities. DISCUSSION: Our systematic evidence map highlights gaps
      in the existing literature, such as a lack of studies in key women's health areas
      (intimate partner violence, mental health), and a dearth of relevant SRs. With
      few existing SRs in this literature, there is an opportunity for examining
      effects, efficiency, and acceptability across studies to inform efforts at
      implementing telehealth for women.

PMID- 30284175
TI  - Oxidative stress does not contribute to the release of proinflammatory cytokines
      through activating the Nod-like receptor protein 3 inflammasome in patients with
      obstructive sleep apnoea.
AB  - PURPOSE: The study was conducted to test the hypothesis that oxidative stress
      leads to the release of proinflammatory cytokines by activating the Nod-like
      receptor protein (NLRP)3 inflammasome in patients with obstructive sleep apnoea
      (OSA). METHODS: The study recruited 247 participants who were divided into cases
      and healthy control groups. OSA patients were subdivided into four subgroups
      according to sex, blood pressure, body mass index (BMI), and severity of disease.
      No significant differences were found between cases and controls with respect to
      age or sex. Peripheral blood samples were collected for analysis after
      examination, and the serum concentrations of oxidative stress (8-isoprostane),
      inflammation (interleukin (IL)-18, IL-1beta, IL-6, tumour necrosis factor (TNF)
      alpha), and NLRP3 inflammasome components (NLRP3, caspase-1, and ASC) were
      detected by enzyme-linked immunosorbent assay. RESULTS: The serum concentrations
      of both oxidative stress and proinflammatory factors were higher in OSA patients
      than healthy controls. Subgroup analysis also revealed significant differences
      according to the apnoea-hypopnea index and BMI. Additionally, correlations were
      identified between 8-isoprostane and proinflammatory factors (IL-1beta, IL-18,
      and TNF-alpha). Multiple regression analysis suggested that sleep parameters and
      BMI affected inflammation. However, no differences were observed in the serum
      level of NLRP3 inflammasome components between patients and controls.
      Furthermore, stratified analysis revealed no additional differences. CONCLUSIONS:
      The current study suggests that oxidative stress leads to inflammation by
      mechanisms other than activation of the NLRP3 inflammasome in OSA patients.
      Furthermore, both sleep apnoea and BMI influenced the serum concentration of
      inflammatory mediators.

PMID- 30284176
TI  - Multiplex testing for Factor II and Factor V mutations in thrombophilia:
      technical verification and clinical validation of the cobas(r) Factor II and
      Factor V test.
AB  - Laboratory testing for thrombophilia is complicated but essential for diagnosis.
      In 2017, the cobas(r) Factor II and Factor V Test (cobas F2F5 test) was launched
      for use with the cobas z 480 analyzer. This qualitative polymerase chain reaction
      test enables multiplex Factor II and Factor V testing with flexible reporting and
      workflow efficiency. Here, we report the results from studies investigating the
      performance of the cobas F2F5 test. Technical performance verification, clinical
      validation, external laboratory performance, and workflow comparison studies were
      performed. Fresh and frozen whole-blood and genomic DNA (gDNA) samples were
      tested, and several manual and automated DNA isolation methods were used.
      Bidirectional Sanger sequencing was used to verify genotypes identified by the
      cobas F2F5 test. One hundred percent agreement between the cobas F2F5 test and
      Sanger sequencing was observed for all genotypes. An external laboratory using
      remnant clinical samples also yielded 100% agreement between cobas F2F5 test
      results and their routine testing method. The cobas F2F5 test reduced the total
      sample processing time compared with the LightCycler(r) 1.2 platform (98.6 vs
      420.2 min; 96 samples). Hemoglobin, extraction buffer, and ethanol contamination
      of the gDNA sample can lead to invalid results. The cobas F2F5 test has a high
      degree of accuracy for identification of Factor II and Factor V genotypes. This
      multiplex testing with short sample processing time can reduce handling errors
      and increase efficiency. Both manual and automated DNA isolation methods can be
      used with the cobas F2F5 test.

PMID- 30284178
TI  - Clinical Pharmacokinetics of Second-Generation Triazoles for the Treatment of
      Invasive Aspergillosis and Candidiasis.
AB  - Second-generation triazoles were developed in response to the quest for more
      efficacious and safer therapeutic options for the treatment of severe systemic
      aspergillosis and candidiasis. These agents include voriconazole, posaconazole,
      isavuconazole, and ravuconazole. The aim of this review was to present and
      compare the pharmacokinetic characteristics of second-generation triazoles for
      the treatment of invasive aspergillosis and candidiasis, emphasizing their
      clinical implications. The MEDLINE, Scopus, EBSCO, Google Scholar, and SCIndeks
      databases were searched using advanced search options, including the names of
      second-generation triazoles and pharmacokinetic terms as keywords. The
      intravenous administration of voriconazole, posaconazole, and isavuconazole
      results in stable pharmacokinetics of these drugs, with mostly predictable
      variations influenced by common and usually known factors in routine clinical
      settings. The high oral bioavailability of isavuconazole and, to some extent,
      voriconazole makes them suitable for intravenous-to-oral switch strategies.
      Except for intravenous voriconazole (due to the accumulation of the toxic vehicle
      hydroxypropyl betadex), dose reduction of second-generation triazoles is not
      needed in patients with renal failure; patients with hepatic insufficiency
      require dose reduction only in advanced disease stages. The introduction of
      therapeutic drug monitoring could aid attempts to optimize the blood
      concentrations of triazoles and other drugs that are known to or that possibly
      interact, thus increasing treatment efficacy and safety. There is a need for new
      studies that are designed to provide useful data on second-generation triazole
      pharmacokinetics, particularly in special circumstances such as central nervous
      system and ocular infections, infections in newborns and infants, and in subjects
      with genetic polymorphisms of metabolizing enzymes.

PMID- 30284177
TI  - Sugar-Sweetened Beverages and Child Health: Implications for Policy.
AB  - PURPOSE OF REVIEW: Various policies to reduce sugar-sweetened beverages (SSBs)
      consumption in children have been implemented. Here, we review the evidence on
      whether these policies are effective in reducing SSB intake and whether a
      reduction in SSB intake results in a concomitant reduction in child obesity. We
      also highlight ethical concerns with such efforts. RECENT FINDINGS: The evidence
      supporting relationship between SSB consumption and child body mass index (BMI)
      is consistently small and lacks causality. The effects of policies are unclear;
      taxation has no clear relationship to SSB purchasing, innovative marketing
      outlets make it difficult to examine the effects of restricting marketing on SSB
      consumption, and there is no evidence that reducing SSB availability in schools
      decreases consumption. Research studies with rigorous and reproducible study
      designs are needed to examine whether reducing SSB consumption reduces child
      obesity, and to identify implementable policies that not only reduce SSB
      consumption but also child weight.

PMID- 30284179
TI  - The association between treatment appropriateness according to EUCAST and CLSI
      breakpoints and mortality among patients with candidemia: a retrospective
      observational study.
AB  - To evaluate the association between appropriate antifungal treatment and
      mortality among patients with candidemia using different breakpoint definitions.
      In a retrospective study, we included all adults with candidemia in a tertiary
      center between 2009 and 2015. We defined three versions of appropriate (covering)
      antifungal treatment, according to Clinical and Laboratory Standards Institute
      (CLSI) 2008, CLSI 2012, and European Committee on Antimicrobial Susceptibility
      Testing (EUCAST) (2017 update) breakpoints. For empiric treatment, we evaluated
      the association with 30-day mortality. For definitive treatment, we evaluated the
      association with 90-day mortality among patients surviving the first week after
      candidemia onset. Adjusted odds ratios (OR) from a bivariate logistic regression
      with 95% confidence intervals are reported. We identified 302 patients with 308
      separate candidemia episodes. The crude 30-day mortality was 55% (168/308).
      Resistance to anidulafungin increased from 3.5 to 51.6% and to fluconazole from
      15.2 to 44.1%, when applying CLSI 2008 and EUCAST definitions, respectively.
      Appropriate empirical treatment was significantly associated with lower 30-day
      mortality using the CLSI 2008 definitions, adjusted OR 0.56 (0.33-0.96). The
      associations were similar, though not statistically significant for EUCAST, 0.58
      (0.33-1.00), and CLSI 2012, OR 0.62 (0.37-1.04). Appropriate definitive treatment
      according to CLSI 2012 and EUCAST was independently associated with lower 90-day
      mortality, ORs 0.31 (0.13-0.75) and 0.44 (0.23-0.8), respectively. With CLSI
      2008, the association was similar but not statistically significant, OR 0.4 (0.11
      1.41), with few isolates classified as resistant. Considering the major shift in
      resistance prevalence when applying CLSI 2008, CLSI 2012, and EUCAST breakpoint
      definitions, no major differences were observed in their association with
      mortality.

PMID- 30284181
TI  - Normative values for the distress thermometer (DT) and the emotion thermometers
      (ET), derived from a German general population sample.
AB  - PURPOSE: The distress thermometer (DT) and the emotion thermometers (ET) are
      short screening instruments for use in oncological practice. The aim of this
      study was to provide normative values and to analyze the correlational structure
      of the ET. METHODS: A representative sample of the adult German general
      population (N = 2437) completed the ET, the PHQ-4, the FACIT-fatigue scale, and
      the demoralization scale. RESULTS: The percentages of people above the cutoff (>=
      4) and the mean scores of the five ET scales were as follows: distress: 39.0%, M
      = 3.15 +/- 2.62, anxiety: 12.3%, M = 1.36 +/- 1.93, depression: 16.1%, M = 1.65
      +/- 2.11, anger: 24.5%, M = 2.33 +/- 2.16, and need for help: 10.7%, M = 1.18 +/-
      1.90. Women reported significantly higher levels of burden than men, with effect
      sizes between 0.07 (anger) and 0.36 (anxiety). All ET dimensions were
      interrelated (r between 0.44 and 0.69) and significantly correlated with the
      other scales (r between 0.36 and 0.68). CONCLUSIONS: The normative scores can
      help qualify assessments of groups of patients. The new four dimensions of the ET
      provide relevant additional information that is not already covered by the DT.

PMID- 30284180
TI  - The Importance of CYP19A1 in Estrogen Receptor-Positive Cholangiocarcinoma.
AB  - CYP19A1, also called aromatase, is a key enzyme for converting androgens to
      estrogens of estrogen synthesis. Elevated serum estrogen and high expression
      levels of estrogen-related proteins are found in cholangiocarcinoma (CCA; bile
      duct cancer). However, the expression of CYP19A1 in relation to estrogen-related
      proteins, including estrogen receptors (ERalpha, ERbeta, and GPR30) and an
      estrogen response protein (TFF1), has never been explored in CCA. In this study,
      we investigated the expressions of CYP19A1 and estrogen-related proteins in CCA
      tissues (n = 74; 51 males and 23 females) using immunohistochemistry. The results
      showed that CYP19A1 was overexpressed in CCA cells compared with that in normal
      bile duct cells in the adjacent tissues. High expression of CYP19A1 was
      correlated with the metastatic status of the patients. High CYP19A1 expression
      was also positively correlated with GPR30 expression. Correlation between high
      CYP19A1 expression in the tumor tissues and shorter survival time was more
      prominent in male than in female CCA patients. To elucidate further, the effect
      of CYP19A1 knockdown on a CCA cell line was examined using a specific siRNA. When
      CYP19A1 gene expression was suppressed, migration and proliferation activities of
      CCA cells were significantly reduced. Moreover, the cell proliferation of high
      CYP19A1-expressing KKU-213 cells was more profoundly suppressed by CYP19A1
      inhibitors (exemestane and letrozole) than low CYP19A1-expressing KKU-100 cells.
      Thus, CYP19A1 promotes CCA progression with aggressive clinical outcomes via
      increased migration and proliferation activities of cancer cells. CYP19A1 can be
      a potential chemotherapeutic target for CCA, especially in male patients.

PMID- 30284182
TI  - Test-retest reliability and validity of a single-item Self-reported Family
      Happiness Scale in Hong Kong Chinese: findings from Hong Kong Jockey Club FAMILY
      Project.
AB  - PURPOSE: Family happiness is one major theme of family well-being in Chinese
      culture. We investigated the reliability and validity of the single-item Self
      reported Family Happiness Scale (SFHS-1) with the score of 0-10, based on two
      studies in Hong Kong Chinese. METHODS: Study 1 was a territory-wide population
      based telephone survey (n = 4038) conducted in 2016. Study 2 was a community
      based family intervention program conducted during 2012-2013 (n = 1261) to
      enhance family communication and well-being. Test-retest reliability of the SFHS
      1 was assessed over 1 month in Study 2. Family APGAR (Adaption, Partnership,
      Growth, Affection, Resolve) Scale, Family Communication Scale, Subjective
      Happiness Scale, 12-item Short Form Health Survey Version 2, and 2-item Patient
      Health Questionnaire were used to assess the convergent and discriminant
      validities of the SFHS-1 in both studies. Multiple regression analysis was used
      to assess the incremental validity by identifying the additional contribution of
      the SFHS-1 score in predicting subjective happiness. RESULTS: The 1-month test
      retest reliability assessed by intraclass correlation was 0.76. Family happiness
      was moderately to strongly correlated with family function, family communication,
      subjective happiness, mental health-related quality of life and depression, but
      weakly correlated with physical health-related quality of life. Furthermore, the
      score of the SFHS-1 added predictive power to mental health-related quality of
      life and depression in assessing subjective happiness. CONCLUSIONS: Our results
      have shown the SFHS-1 as a reliable and valid measurement of family happiness in
      Hong Kong Chinese, suggesting SFHS-1 is highly practicable for future large
      epidemiological and community-based intervention studies.

PMID- 30284183
TI  - A systematic review of randomised controlled trials evaluating the use of patient
      reported outcome measures (PROMs).
AB  - BACKGROUND: Patient-reported outcome measures (PROMs) could play an important
      role in identifying patients' needs and goals in clinical encounters, improving
      communication and decision-making with clinicians, while making care more patient
      centred. Comprehensive evidence that PROMS are an effective intervention is
      lacking in single randomised controlled trials (RCTs). METHODS: A systematic
      search was performed using controlled vocabulary related to the terms: clinical
      care setting and patient-reported outcome. English language studies were included
      if they were a RCT with a PROM as an intervention in a patient population.
      Included studies were analysed and their methodologic quality was appraised using
      the Cochrane Risk of Bias tool. The protocol was registered with PROSPERO
      (CRD42016034182). RESULTS: Of 4302 articles initially identified, 115 underwent
      full-text review resulting in 22 studies reporting on 25 comparisons. The
      majority of included studies were conducted in USA (11), among cancer patients
      (11), with adult participants only (20). Statistically significant and robust
      improvements were reported in the pre-specified outcomes of the process of care
      (2) and health care (3). Additionally, five, eight and three statistically
      significant but possibly non-robust findings were reported in the process of
      care, health and patient satisfaction outcomes, respectively. CONCLUSIONS:
      Overall, studies that compared PROM to standard care either reported a positive
      effect or were not powered to find pre-specified differences. There is
      justification for the use of a PROM as part of standard care, but further
      adequately powered studies on their use in different contexts are necessary for a
      more comprehensive evidence base.

PMID- 30284184
TI  - Pull-down maneuver of stent graft for abdominal aortic aneurysm with accessory
      renal arteries.

PMID- 30284185
TI  - 1H, 13C and 15N NMR assignments of self-incompatibility protein homologue 15 from
      Arabidopsis thaliana.
AB  - The SPH proteins are a large family of small, disulphide-bonded, secreted
      proteins, originally found to be involved in the self-incompatibility response in
      the field poppy (Papaver rhoeas). They are now known to be widely distributed in
      plants, many containing multiple members of this protein family. Apart from the
      PrsS proteins in Papaver the function of these proteins is unknown but they are
      thought to be involved in plant development and cell signalling. There has been
      no structural study of SPH proteins to date. Using the Origami strain of E. coli,
      we cloned and expressed one member of this family, SPH15 from Arabidopsis
      thaliana, as a folded thioredoxin-fusion protein, purified it from the cytosol,
      and cleaved it to obtain the secreted protein. We here report the assignment of
      the NMR spectra of SPH15, which contains 112 residues plus three N-terminal amino
      acids from the vector. The secondary structure propensity from TALOS+ shows that
      it contains eight beta strands and connecting loops. This is largely in agreement
      with predictions from the amino acid sequence, which show an additional C
      terminal strand.

PMID- 30284186
TI  - Uncertainty Quantification for Non-invasive Assessment of Pressure Drop Across a
      Coarctation of the Aorta Using CFD.
AB  - PURPOSE: Numerical assessment of the pressure drop across an aortic coarctation
      using CFD is a promising approach to replace invasive catheter-based
      measurements. The aim of this study was to investigate and quantify the
      uncertainty of numerical calculation of the pressure drop introduced during two
      essential steps of medical image processing: segmentation of the patient-specific
      geometry and measurement of patient-specific flow rates from 4D-flow-MRI.
      METHODS: Based on the baseline segmentation, geometries with different stenosis
      diameters were generated for a sample of ten patients. The pressure drop
      generated by these geometries was calculated for different volume flow rates
      using computational fluid dynamics. Based on these simulations, a second order
      polynomial fit was calculated. Based on these polynomial fits an uncertainty of
      pressure drop calculation was quantified. RESULTS: The calculated pressure drop
      values varied strongly between the patients. In four patients, pressure drops
      above and below the clinical threshold of 20 mmHg were found. The median standard
      deviation of the pressure drop was 2.3 mmHg. The sensitivity of the pressure drop
      toward changes in the volume flow rate or the stenosis geometry varied between
      patients. CONCLUSION: The uncertainty of numerical pressure drop calculation
      introduced by uncertainties during image segmentation and measurement of volume
      flow rates was comparable to the uncertainty of pressure drop measurements using
      invasive catheterization. However, in some patients this uncertainty would have
      led to different treatment decision. Therefore, patient-specific uncertainty
      assessment might help to better understand the reliability of a numerically
      calculated biomarker as the pressure drop across an aortic coarctation.

PMID- 30284187
TI  - An integrative review of factors that influence reproductive decisions in women
      with sickle cell disease.
AB  - Sickle cell disease is one of the most prevalent genetic diseases in the world.
      Improvements in care have enabled those affected to experience an improved
      quality of life, with many affected persons now reaching reproductive age.
      However, pregnancy poses significant risks for women with the disease and this
      may affect their reproductive decisions. We conducted an integrative review of
      the published relevant scientific evidence to ascertain the factors that may
      influence these women with their reproductive decisions. The electronic databases
      MEDLINE, CINAHL, and PsychInfo and relevant journals were searched for peer
      reviewed papers published between 2005 and 2015. Of the 440 papers identified,
      six papers satisfied the inclusion criteria and were assessed for quality.
      Results were analysed and synthesised using a thematic approach to produce a
      narrative report of the findings. Two main themes were identified: (1) factors
      influencing reproductive decision-making and (2) experiences during pregnancy.
      Education regarding disease knowledge and genetic implications may improve
      participation into screening programmes, facilitate the effective treatment
      needed to create trust in healthcare services, and promote better self
      management. Educating professionals involved in family planning will facilitate
      women with this condition to make informed decisions regarding pregnancy.
      However, further research is required to explore the understanding of the risks
      involved with sickle cell disease, the best methods to educate people with sickle
      cell disease, and the influence that partners and families may have on women's
      reproductive decisions.

PMID- 30284188
TI  - Methyl Jasmonate Changes the Composition and Distribution Rather than the
      Concentration of Defence Compounds: a Study on Pyrrolizidine Alkaloids.
AB  - In this study we investigated the effect of methyl jasmonate (MeJA) application
      on pyrrolizidine alkaloid (PA) concentration and composition of two closely
      related Jacobaea species. In addition, we examined whether MeJA application
      affected herbivory of the polyphagous leaf feeding herbivore Spodoptera exigua. A
      range of concentrations of MeJA was added to the medium of Jacobaea vulgaris and
      J. aquatica tissue culture plants grown under axenic conditions. PA
      concentrations were measured in roots and shoots using LC-MS/MS. In neither
      species MeJA application did affect the total PA concentration at the whole plant
      level. In J. vulgaris the total PA concentration decreased in roots but increased
      in shoots. In J. aquatica a similar non-significant trend was observed. In both
      Jacobaea species MeJA application induced a strong shift from senecionine- to
      erucifoline-like PAs, while the jacobine- and otosenine-like PAs remained largely
      unaffected. The results show that MeJA application does not necessarily elicits
      de novo synthesis, but rather leads to PA conversion combined with reallocation
      of certain PAs from roots to shoots. S. exigua preferred feeding on control
      leaves of J. aquatica over MeJA treated leaves, while for J. vulgaris both the
      control and MeJA treated leaves were hardly eaten. This suggests that the MeJA
      induced increase of erucifoline-like PAs can play a role in resistance of J.
      aquatica to S. exigua. In J. vulgaris resistance to S. exigua may already be high
      due to the presence of jacobine-like PAs or other resistance factors.

PMID- 30284189
TI  - Forward and backward recall of serial actions: Exploring the temporal dynamics of
      working memory for instruction.
AB  - The ability to flexibly retrieve and implement sequences of actions is essential
      to motor learning and planning. Recent research has indicated that serial memory
      for instructions is influenced by presentation modality (spoken vs. visual
      demonstration) and recall modality (verbal vs. enacted recall). The present study
      extended this work by investigating the impact of recall direction (forward vs.
      backward), in addition to that of presentation and recall modality, on working
      memory for instruction sequences in healthy young adults. Experiment 1 (N = 24)
      showed that adults were more accurate in backward than forward verbal recall
      following spoken instructions. In contrast, enacted recall was not influenced by
      recall direction. Experiment 2 (N = 24) used visual demonstration of instruction
      sequences and found similar performance levels in forward and backward recall.
      Experiment 3 (N = 24) replicated the findings from Experiment 1 and 2, along with
      the previous observation of an advantage for demonstrated over spoken
      presentation. In addition, the beneficial effects of enacted recall and visual
      demonstration also emerged in an analysis of response times, specifically in
      reduced preparation and recall duration. Demonstrated instructions improved
      maintenance of all items while backward recall enhanced memory of later items in
      the sequence. These findings provide new insights into the cognitive processes
      and temporal dynamics of working memory for serial actions and instructions.

PMID- 30284191
TI  - Molecular modeling investigation of the potential mechanism for phytochemical
      induced skin collagen biosynthesis by inhibition of the protein phosphatase 1
      holoenzyme.
AB  - The most prominent feature of UV-induced photoaged skin is decreased type 1
      procollagen. Increase of the TGF-beta/Smad signaling through inhibition of the
      TbetaRI dephosphorylation by the GADD34-PP1c phosphatase complex represents a
      promising strategy for the increase in type 1 collagen production and prevention
      of UV-induced skin photoaging. In this study, the molecular docking and dynamics
      simulations, and pharmacophore modeling method were run to investigate a possible
      binding site as well as binding modes between apigenin, daidzein, asiaticoside,
      obovatol, and astragaloside IV and PP1c. Through docking study, the possible
      binding site for these phytochemicals was predicted as the hydrophobic (PP1
      substrate binding) groove. The result indicates that PP1 is the significant
      target of these compounds. Moreover, the 20,000-ps MD simulations present that
      the binding locations and modes predicted by the docking have been slightly
      changed considering that the MD simulations proffer more reliable details upon
      the protein-ligand recognition. The MM-GBSA binding free energy calculations and
      pharmacophore modeling rationally identify that the highly hydrophobic
      surfaces/pockets at close proximity of the catalytic core are the most favorable
      binding locations of the herbal compounds, and that some experimental facts upon
      a possible mechanism of increase in collagen biosynthesis can be explained. The
      present study theoretically offers the reliable binding target of the herbal
      compounds, and therefore helps to understanding the action mechanism for natural
      small molecules that enhance collagen production.

PMID- 30284190
TI  - Heterobucephalopsine and prosorhynchine trematodes (Digenea: Bucephalidae) from
      teleost fishes of Moreton Bay, Queensland, Australia, with the description of two
      new species.
AB  - Eight species of the trematode family Bucephalidae Poche, 1907 are reported from
      teleost fishes in Moreton Bay, Queensland, Australia. Heterobucephalopsis yongi
      n. sp. is described from Gymnothorax eurostus (Muraenidae); the new form is
      distinguished from its congeners in the possession of a tiny cirrus-sac relative
      to body length, the length of the caecum, the position of the mouth and pharynx,
      and the position of the testes and ovary. Two known species of Dollfustrema
      Eckmann, 1934, D. durum Nolan, Curran, Miller, Cutmore, Cantacessi & Cribb, 2015
      and D. gibsoni Nolan & Cribb, 2010, are reported from Gymnothorax
      pseudothyrsoideus (Bleeker) (Muraenidae); although both species were described
      from Australian waters, this represents the first reports from Moreton Bay and G.
      pseudothyrsoideus. Four species of Prosorhynchus Odhner, 1905 are reported,
      including one new, P. brayi n. sp., which is described from Epinephelus coioides
      (Hamilton) (Serranidae); P. brayi n. sp. is distinguished from its congeners in
      the possession of vitelline follicles in a confluent arc distinctly posterior to
      a conical rhynchus, uterine coils that do not extend anterior to the vitelline
      arc, contiguous testes, a cirrus-sac that reaches anteriorly to at least the
      level of the posterior testis and a short excretory vesicle. Three known species
      of Prosorhynchus are reported from Australia, for the first time: P. luzonicus
      Velasquez, 1959 and P. maternus Bray & Justine, 2006 from E. coioides and
      Prosorhynchus platycephali (Yamaguti, 1934) Srivastava, 1938 from Ambiserrula
      jugosa (McCulloch) and Inegocia japonica (Cuvier) (Platycephalidae).
      Skrjabiniella Issaitschikow, 1928 is re-recognised for new specimens of
      Skrjabiniella uniporus (Ozaki, 1924) n. comb. collected from Conger cinereus
      Ruppell (Congridae); three additional species of Prosorhynchus are considered
      members of this genus, two of which are synonymised with S. uniporus.

PMID- 30284192
TI  - Exhaustive exercise decreases renal organic anion transporter 3 function.
AB  - This study aimed to investigate the effects of various types of exercise on
      organic anion transporter 3 (Oat3) function, a major transporter that plays a
      role in the secretion of a variety of drugs and endogenous compounds. Male Wistar
      rats were randomly allocated to non-exercise, exhaustive, acute and training
      exercise groups. The function of Oat3 was assessed by the uptake of [3H]-estrone
      sulfate ([3H]-ES) into rat renal cortical slices. Acute and training exercises
      had no effect on [3H]-ES uptake whereas a marked reduction in [3H]-ES uptake
      occurred immediately after exhaustive exercise. However, the reduction in Oat3
      function was gradually recovered at 6 and 24 h after the exercise session.
      Importantly, the impairment of Oat3 function was associated with a decrease in
      renal Oat3 protein expression. Our results indicate that exhaustive exercise
      produces a significant impact on renal organic anion transport function, which in
      turn could alter the plasma level of drugs and compounds in the body.

PMID- 30284194
TI  - Additive effect of metastamiR-193b and breast cancer metastasis suppressor 1 as
      an anti-metastatic strategy.
AB  - BACKGROUND: It has been reported that enhancing the cellular levels of miR-193b
      as well as breast cancer-metastasis-suppressor-1 (BRMS1) protein is associated
      with diminished metastatic characteristics in breast cancer. In view of these
      facts, as a new therapeutic intervention, we employed a restoration-based
      strategy using both miR-193b-3p mimic and optimized BRMS1 in the context of a
      chimeric construct. METHODS: miR-193b-3p and BRMS1 genes were cloned and the
      resulting plasmids were transfected into the MDA-MB231, MCF-7 and MCF-10A cell
      lines. microRNA expression levels were assessed by rea time PCR using LNA-primer
      and protein expression was confirmed by western blot method. Then, apoptosis,
      MTT, colony formation and invasion assays were carried out. RESULTS: The
      expression levels of miR-146a, miR-146b and miR-373 were up-regulated, while the
      miR-520c, miR-335 and miR-10b were down-regulated following the exogenous BRMS1
      expression. The exogenous over-expression of BRMS1 was associated with higher
      amounts of endogenous miR-193b-3p expression and enabled more efficient targeting
      of the 3'UTR of uPA. Although, miR-193b-3p and BRMS1 are individually capable of
      suppressing breast cancer cell growth, migration and invasion abilities, their
      cistronic expression was capable of enhancing the ability to repress the breast
      cancer cells invasion. CONCLUSIONS: Our results collectively indicated the
      existence of an additive anti-metastatic effect between miR-193b-3p and BRMS1.
      Moreover, it has been hypothesized that the exogenous expression of a protein can
      effect endogenous expression of non-relevant microRNA. Our findings provide new
      grounds for miR-restoration therapy applications as an amenable anti-metastatic
      strategy.

PMID- 30284193
TI  - Psychosocial Mediators of Change and Patient Selection Factors in Oral
      Immunotherapy Trials.
AB  - Health-related quality of life (HRQL) is influenced by physiological,
      psychological, and environmental variables and can be best understood by
      considering the interactions of factors that cut across multiple levels. One of
      the most important issues relating to treatment in food allergy is to identify,
      describe, and define predictors that may contribute to modify HRQL outcomes. The
      research presented demonstrates that measures of HRQL are able to distinguish key
      features of known groups (e.g. relating to reaction severity, treatment, allergen
      type/number, expectation of outcome) and delineate impact on hitherto unknown
      groups (e.g. relating to personality types and coping styles). This heterogeneity
      may explain why HRQL or other patient-related outcomes may differ in individuals
      during, or following any treatment or intervention. Patient-reported outcomes are
      relatively poorly defined to date. Since HRQL has only been studied in relatively
      few oral immunotherapy trials to date, primarily looking at caregiver HRQL, it is
      unclear which factors, measures, or subscales are most predictive of short-
      and/or long-term treatment outcomes for which type of patient, and which time
      points for measurement are most informative. A standardised protocol that
      incorporates HRQL and other relevant patient-related outcome measures and agreed
      definitions of outcomes would allow for the comparison of efficacy of food
      allergy treatments between centres, trials, or countries. Further evidence-based
      research aimed at exploring the effects of interventions on outcomes in food
      allergy is needed, including the influence of patient and parent factors on
      protocol design. To this end, it is vital that patient-related outcomes such as
      improved HRQL are seen as a primary outcome and are measured at multiple
      intervals during the trial duration and beyond. The creative use of methods and
      designs (both qualitative and quantitative) to better understand the role of HRQL
      in immunotherapy treatment trials will enable improved modelling of the costs,
      risks, and benefits of any treatment. Systematic analysis and modelling of
      antecedent factors, mediators, and outcomes will be important to boost
      intervention effects and to maximise the overall benefits of treatment.

PMID- 30284196
TI  - Size does matter: when a large plastic biliary stent ends up in the root of the
      mesentery.
AB  - Duodenal perforations due to biliary stenting migration, although rare, can
      occur. We report a unique case of duodenal perforation due to a large in length
      plastic stent with no (or marginal) migration, which ended up in the root of the
      mesentery, explaining the normal laboratory values and minimal imaging findings
      observed. Any clinical symptom during the postprocedural period should raise the
      suspicion of a major complication and prompt quick management decisions.

PMID- 30284197
TI  - U-turn of uterine arteries: a novel sign pathognomonic of uterine inversion.
AB  - A uterine inversion occurs when the uterine fundus collapses into the endometrial
      cavity. It is a rare complication in obstetrics following delivery, and it is
      even more infrequently encountered in gynecology with the non-puerperal uterus. A
      submucous fibroid is the most common reported cause of the non-puerperal uterine
      inversion. If not promptly recognized and treated, uterine inversion may lead to
      a severe hemorrhagic shock and death. We describe a novel three-dimensional power
      Doppler feature for the diagnosis of uterine inversion.

PMID- 30284198
TI  - Severe Biliary Stricture Dilation Using the Soehendra Stent Retriever with a
      Short-Type Balloon Enteroscope in Patients with Surgically Altered Anatomies.
AB  - BACKGROUND: Balloon enteroscopy (BE) can be used for endoscopic retrograde
      cholangiography (ERC) to treat biliary strictures in patients with surgically
      altered anatomies. However, biliary strictures, including bilioenteric
      anastomotic strictures, are often very severe and dilation catheters cannot pass
      through them. The Soehendra stent retriever (SSR) is like a screw drill and can
      be useful for dilating severe strictures, but the utility of SSR during BE
      assisted ERC (BE-ERC) is unclear. This study aimed to examine the efficacy and
      safety of a dilation technique using the SSR during BE-ERC. METHODS: Between 2014
      and 2018, 28 patients with surgically altered gastrointestinal anatomies and
      severe biliary strictures underwent BE-ERC, and the SSR was used for the dilation
      procedures. We evaluated the technical success, therapeutic success, and adverse
      event rates associated with SSR dilation. RESULTS: The technical success rate was
      93% (26/28). The procedures undertaken on two patients with non-anastomotic
      strictures failed technically because the SSR was not long enough to reach the
      strictures. The therapeutic success rate was 96% (25/26) for the patients whose
      procedures were technically successful. The adverse event rate was 7% (2/28), and
      the adverse events were mild and improved with conservative management. No
      bleeding or duct perforations occurred. CONCLUSIONS: Although the indications for
      using the SSR in patients with non-anastomotic strictures should be considered
      based on the distance between the tip of the scope and the stricture's location,
      SSR dilation may be a useful option during BE-ERC if a biliary stricture is very
      severe.

PMID- 30284195
TI  - Recent Progress in Sarcopenia Research: a Focus on Operationalizing a Definition
      of Sarcopenia.
AB  - PURPOSE OF REVIEW: To discuss recent progress in sarcopenia research and to
      highlight controversies in the field particularly around reaching consensus on a
      definition of sarcopenia. RECENT FINDINGS: Accordingly, this review begins with a
      discussion of the increasing awareness of this condition; briefly describes
      evolving definitions of sarcopenia; suggests a framework for consistent
      terminology for sarcopenia; discusses outstanding issues in the definition of
      sarcopenia; and reviews the association between sarcopenia and adverse outcome in
      older adults. In addition, the role of sarcopenia in other diseases is discussed.
      The field of sarcopenia continues to hold considerable promise and work continues
      to resolve outstanding concerns in this field with a unifying consensus
      definition on the horizon.

PMID- 30284199
TI  - The Impact of a Multivisceral Resection and Adjuvant Therapy in Locally Advanced
      Colon Cancer.
AB  - BACKGROUND: Multivisceral resection for locally advanced colon cancer is
      mandatory to achieve complete tumor resection. We aimed to determine if local
      multivisceral resections (LMR) for pT4 and pT3 tumors impact perioperative and
      long-term oncological outcomes. METHODS: All stage II or III colon cancer
      patients who had surgery between 2004 and 2014 were identified. We analyzed
      patients with non-multivisceral resections (NMR) for pT4 tumors vs. pT4-LMR. In
      addition, outcomes were compared to both NMR and LMR pT3 patients. RESULTS: LMR
      was performed in 55 (29.7%) of all patients with pT4 tumors and in 48 (8.9%) of
      all patients with pT3 tumors. The most commonly involved areas of extension were
      the abdominal wall and the small intestine. Transverse colon cancer was
      correlated with LMR. Morbidity rates were comparable between NMR and LMR, with
      the exception of higher rates of blood transfusion and postoperative ileus. Over
      one third of all pT4-NMR patients developed recurrent disease, which was higher
      compared to all other groups. Subsequently, overall and disease-specific
      survival, as well as disease-free survival (DFS), was worse for pT4-NMR, even
      after adjustment for pTN-staging, adjuvant therapy, and R0 resection.
      Furthermore, when analyzing only curative resections, radial margin < 1 cm along
      with nodal disease was independent predictor for worse DFS. Long-term outcomes
      were comparable between pT4-LMR and pT3 patients. CONCLUSIONS: Multivisceral
      resection for locally advanced colon cancer preserves long-term oncological
      outcomes without increased postoperative morbidity. Moreover, LMR in pT3 tumors
      does not contribute to postoperative morbidity. Our study underlines the
      feasibility and importance of performing LMR when locally advanced cancer is
      suspected.

PMID- 30284200
TI  - Laparoscopic Resection for Adenocarcinoma of the Stomach or Gastroesophageal
      Junction Improves Postoperative Outcomes: a Propensity Score Matching Analysis.
AB  - BACKGROUND: Minimally invasive resection for upper gastrointestinal tumors has
      been associated with favorable results. However, the role of laparoscopic surgery
      (LS) in the multimodal treatment of patients with advanced adenocarcinoma of the
      stomach or gastroesophageal junction needs further investigation. METHODS:
      Clinicopathological data of patients who underwent gastrectomy between 2005 and
      2017 were assessed. Outcomes of patients undergoing LS were compared with those
      of patients treated with a conventional open resection (OR) using a 1:1
      propensity score matching analysis. RESULTS: Curative resection for
      adenocarcinoma of the stomach or gastroesophageal junction was performed in 417
      patients during the study period. Beginning in June 2014, the majority of
      patients underwent LS (n = 72) and they were matched with 72 patients who were
      treated with an OR. The majority of patients treated with LS (89%) had advanced
      cancer (UICC stages II and III) and 82% of them received neoadjuvant
      chemotherapy. LS was significantly associated with a higher number of harvested
      lymph nodes (26 (9-62) vs. 21 (4-46), P = .007), a lower 90-day major
      complication rate (13 vs. 26%, P = .035), and a lower length of hospital stay (14
      vs. 16 days, P = .001). After a median follow-up time of 32 months, 1-year
      overall survival rate was higher after LS than after OR (93 vs. 74%, P = .126);
      however, results did not reach statistical significance. CONCLUSION: LS for
      adenocarcinoma of the stomach or gastroesophageal junction is feasible and
      significantly reduces major postoperative morbidity resulting in a reduced length
      of hospital stay. Therefore, LS should be preferably considered for the curative
      treatment of patients with these malignancies.

PMID- 30284202
TI  - Gastric Intussusception Secondary to Fundic Gland Polyposis.

PMID- 30284201
TI  - Urgent Management of Obstructing Colorectal Cancer: Divert, Stent, or Resect?
AB  - Despite the availability of effective colorectal cancer (CRC) screening
      strategies, up to 10% of CRC patients present with obstructive symptoms as the
      first sign of disease. For patients with acute or subacute malignant obstruction
      that requires urgent intervention, treatment options include endoscopic stenting
      as a bridge to surgery, one-stage surgical resection and anastomosis, or
      diverting ostomy which may or may not be followed by later tumor resection and
      stoma closure. However, to date, there is no consensus guideline for the optimal
      approach to manage malignant colorectal obstruction. This article aims to
      illustrate clinical scenarios in palliative, curative, and potentially curative
      settings, and delineate the key factors to be considered when making an
      individualized decision in order to determine the optimal treatment.

PMID- 30284204
TI  - Development of a Human APOE Knock-in Mouse Model for Study of Cognitive Function
      After Cancer Chemotherapy.
AB  - Cancer-related cognitive impairment in breast cancer patients exposed to multi
      agent chemotherapy regimens is associated with the apolipoprotein E4 (APOE4)
      allele. However, it is difficult to determine the effects of specific agents on
      cognitive impairment in human studies. We describe the development of a human
      APOE knock-in congenic C57BL/6J mouse model to study cancer-related cognitive
      impairment. Female APOE3 and APOE4 homozygous mice were either left untreated or
      treated with the most commonly used breast cancer therapeutic agent, doxorubicin.
      APOE3 and APOE4 mice had similar behaviors in exploratory and anxiety assays,
      which were affected transiently by doxorubicin treatment. Spatial learning and
      memory were measured in a Barnes maze: after 4 days of training, control APOE3
      and APOE4 mice were able to escape with similar latencies. In contrast,
      doxorubicin-treated APOE4 mice had markedly impaired learning compared to
      doxorubicin-treated APOE3 mice at all time points. Voxel-based morphometry of
      magnetic resonance images revealed that doxorubicin treatment caused significant
      changes in the cortex and hippocampus of in both APOE3 and APOE4 mouse brains,
      but the differences were significantly greater in the APOE4 brains. The results
      indicate that doxorubicin-exposed APOE4 mice recapitulate key aspects of human
      cancer-related cognitive impairment. These data support the usefulness of this
      novel preclinical model for future elucidation of the genetic and molecular
      interactions of APOE genotype with chemotherapy; this model can also allow
      extension to prospective studies of older mice to study these interactions in the
      context of aging.

PMID- 30284203
TI  - Long non-coding RNA MEG3 regulates proliferation, apoptosis, and autophagy and is
      associated with prognosis in glioma.
AB  - PURPOSE: Accumulating evidence indicates that dysregulated long noncoding RNAs
      (lncRNAs) play critical roles in tumorigenesis and cancer progression. LncRNA
      maternally expressed gene 3 (MEG3) has been shown to be involved in the
      initiation and development of several cancers, including glioma. However, the
      clinical prognostic value of MEG3 in glioma has not yet been fully elucidated.
      METHODS: The expression levels of MEG3 were detected in 79 glioma tissues and
      adjacent normal brain tissues, as well as, glioma cells and normal human
      astrocytes by qRT-PCR. Kaplan-Meier and Cox regression methods were utilized for
      the survival analysis. MTT assay, flow cytometry, and immunofluorescence assay
      were carried out to detect the impact of MEG3 on glioma cell proliferation,
      apoptosis, and autophagy. RESULT: The current results showed that MEG3 expression
      was significantly downregulated in glioma tissues and cell line and negatively
      correlated with WHO grade in glioma patients. Low MEG3 expression was
      significantly associated with the advanced WHO grade, low Karnofsky performance
      score (KPS), IDH wild-type, and tumor recurrence. Patients displaying a low
      expression of MEG3 contributed to poor overall survival. The downregulated level
      of MEG3, advanced WHO grade, low KPS, IDH wild-type, and tumor recurrence were
      independent poor prognostic indicators in glioma patients. The in vitro
      experiments demonstrated that the MEG3 overexpression remarkably suppressed the
      proliferation while facilitating apoptosis and autophagy in glioma cells.
      CONCLUSIONS: These findings indicated a critical role of MEG3 in glioma cell
      proliferation, apoptosis, and autophagy. Also, the gene was found to be
      significantly associated with the prognosis in glioma patients. Thus, it might
      provide a new target for predicting prognosis and therapeutic intervention in
      glioma.

PMID- 30284206
TI  - Non-adenomatous sellar lesions: single-centre 10-year experience.
AB  - OBJECTIVE: A minority of lesions found in the sellar region are non-adenomatous
      neoplastic, inflammatory, or cystic masses. Our study aims to describe the
      prevalence and characteristics of these lesions in a multidisciplinary pituitary
      outpatient clinic. DESIGN: We conducted an observational study which included 36
      patients (15.9% of those followed up in this outpatient clinic between 2006 and
      2016 who had pituitary surgery) submitted to pituitary surgery with histological
      results showing a non-adenomatous sellar lesion. We evaluated clinical,
      radiological, and biochemical (pituitary function) characteristics during the pre
      operative and post-operative period. RESULTS: Thirty-six patients (50% female)
      with a mean age of 41.3 +/- 21.9 years and a mean follow-up duration of 8.0 +/-
      9.0 years were included. Histologic diagnoses were divided into benign neoplasms
      (80.6%), malignant neoplasms (11.1%), inflammatory lesions (5.6%), and cystic
      masses (2.8%). The most common clinical presentation was headache (66.7%) and
      visual defects (61.1%). Forty-seven percent of patients had at least one
      pituitary axis insufficiency at the time of diagnosis. In the majority of cases
      (58.3%), a transsphenoidal approach was used for the initial pituitary surgery.
      Thirteen patients had more than one pituitary surgery and eight also had
      radiotherapy. At the time of data retrieval, five patients had no pituitary
      hormonal insufficiency and 13 patients had some visual defect improvement.
      CONCLUSIONS: Although rare, non-adenomatous sellar lesions may be associated with
      significant causes of morbidity, such as hypopituitarism and visual defects, per
      se or due to the various treatment modalities employed. Moreover, since the
      lesions are difficult to distinguish from adenomas, these patients require a
      careful multidisciplinary approach.

PMID- 30284205
TI  - Sequence Ion Structures and Dissociation Chemistry of Deprotonated Sucrose
      Anions.
AB  - We investigate the tandem mass spectrometry of regiospecifically labeled,
      deprotonated sucrose analytes. We utilize density functional theory calculations
      to model the pertinent gas-phase fragmentation chemistry of the prevalent
      glycosidic bond cleavages (B1-Y1 and C1-Z1 reactions) and compare these
      predictions to infrared spectroscopy experiments on the resulting B1 and C1
      product anions. For the C1 anions, barriers to interconversion of the pyranose
      [alpha-glucose-H]-, C1 anions to entropically favorable ring-open aldehyde
      terminated forms were modest (41 kJ mol-1) consistent with the observation of a
      band assigned to a carbonyl stretch at ~ 1680-1720 cm-1. For the B1 anions, our
      transition structure calculations predict the presence of both deprotonated 1,6
      anhydroglucose and carbon 2-ketone ((4S,5S,6R)-4,5-dihydroxy-6
      (hydroxymethyl)dihydro-2H-pyran-3(4H)-one) anion structures, with the latter
      predominating. This hypothesis is supported by our spectroscopic data which show
      diagnostic bands at 1600, 1674, and 1699 cm-1 (deprotonated carbon 2-ketone
      structures), and at ~ 1541 cm-1 (both types of structure) and RRKM rate
      calculations. The deprotonated carbon 2-ketone structures are also the lowest
      energy product B1 anions. Graphical Abstract ?.

PMID- 30284207
TI  - A Study of the Activity of Recombinant Mn-Superoxide Dismutase in the Presence of
      Gold and Silver Nanoparticles.
AB  - Superoxide dismutase (SOD) is one of the best characterized enzyme maintaining
      the redox state in the cell. A bacterial expression system was used to produce
      human recombinant manganese SOD with a His-tag on the C-end of the protein for
      better purification. In addition, gold and silver nanoparticles were chemically
      synthesized in a variety of sizes, and then mixed with the enzyme for
      immobilization. Analysis by dynamic light scattering and scanning transmission
      electron microscopy revealed no aggregates or agglomerates of the obtained
      colloids. After immobilization of the protein on AuNPs and AgNPs, the conjugates
      were analyzed by SDS-PAGE. It was determined that SOD was adsorbed only on the
      gold nanoparticles. Enzyme activity was analyzed in colloids of the gold and
      silver nanoparticles bearing SOD. The presence of a nanoparticle did not affect
      enzyme activity; however, the amount of protein and size of the gold nanoparticle
      did influence the enzymatic activity of the conjugate. Our findings confirm that
      active recombinant human superoxide dismutase can be produced using a bacterial
      expression system, and that the enzyme can be immobilized on metal nanoparticles.
      The interaction between enzymes and metal nanoparticles requires further
      investigation.

PMID- 30284208
TI  - A Fiber Optic Biosensor Based on Hydrogel-Immobilized Enzyme Complex for
      Continuous Determination of Cholesterol and Glucose.
AB  - A multiparameter fiber optic biosensor for continuous determination of
      cholesterol and glucose was developed. This sensor was based on poly(N
      isopropylacrylamide) (PNIPAAm)-immobilized glucose oxidase (GOx) complex (PIGC)
      and immobilized cholesterol oxidase (COD). The immobilized COD catalysis to the
      oxidation of cholesterol and PIGC catalysis to the oxidation of glucose could be
      performed at different temperatures. Therefore, the sensor could detect
      cholesterol and glucose continuously by changing temperature. The optimal
      detection conditions for glucose were achieved with pH 6.5, 30  degrees C, and 10
      mg GOx (in 100-mg carrier), and those for cholesterol were achieved with pH 7.5,
      33  degrees C, and 25 mg COD (in 250-mg carrier). The sensor has the cholesterol
      detection range of 20-250 mg/dL and the glucose detection range of 50-700 mg/dL.
      This biosensor has outstanding repeatability and selectivity, and the detection
      results of the practical samples are satisfactory.

PMID- 30284210
TI  - One-Step Enzymatic Synthesis of 1-Tuliposide A Using Tuliposide-Converting
      Enzyme.
AB  - 6-Tuliposides A (6-PosA) and B (6-PosB) are major secondary metabolites in tulip
      (Tulipa gesneriana), having an acyl group at the C-6 position of D-glucose. They
      serve as precursors of the antimicrobial alpha-methylene-gamma-butyrolactones
      tulipalins A (PaA) and B (PaB). The conversions of 6-PosA/6-PosB to PaA/PaB are
      catalyzed by tuliposide-converting enzymes A and B (TCEA and TCEB), respectively.
      A minor Pos, 1-PosA, which has the acyl group at the C-1 position of D-glucose,
      has been identified in some wild tulip species, but availability of this compound
      is limited. Here, by using the TCEs, we established a facile enzymatic process
      for 1-PosA synthesis from the naturally occurring 1,6-diacyl-glucose type of Pos
      (PosD and PosF). We first discovered that TCEA and TCEB react preferentially with
      PosD and PosF, respectively, to form 1-PosA and the corresponding Pa derived from
      the 6-acyl group, demonstrating that the TCEs specifically acted on the 6-acyl
      group, but not the 1-acyl group, of the substrates. Using TCEB, 300 mg of PosF
      was completely converted to 1-PosA and PaB in 10 min at room temperature. Then,
      160 mg of 1-PosA (75% molar yield) was purified by column chromatography. This
      one-step enzymatic process dramatically improves accessibility to 1-PosA.

PMID- 30284209
TI  - Citric Acid Production from Acorn Starch by Tannin Tolerance Mutant Aspergillus
      niger AA120.
AB  - In this study, acorn starch was investigated as a new material for fermenting
      production of citric acid by using a tannin tolerance mutant strain Aspergillus
      niger AA120. The mutant A. niger AA120 was obtained by initially atmospheric
      pressure plasma at room temperature (ARTP) mutagenesis and then tannin gradient
      domestication. ARTP experiments showed that a "double-saddle" shape of survival
      rate curve was achieved, and a positive mutation rate of 63.6% was reached by
      setting the implantation time of mutagenesis to 100 s. In contrast to the
      original stain at the presence of 20.0 g/L tannin in the medium, the selected
      mutant A. niger AA120 exhibits an increase of biomass by 43.76% to 32.9 g/L, and
      citric acid production capacity by 20.34% to 130.8 g/L, with 8% (w/w) of
      inoculation quantity, an initial pH of 6.2 and shaking speed of 250 r/min. In
      this work, we present a referable method for the mutagenesis screening of the A.
      niger, and the application of acorn starch as a new raw material for the
      development of the citric acid industry.

PMID- 30284211
TI  - LAB: Linguistic Annotated Bibliography - a searchable portal for normed database
      information.
AB  - This article presents the Linguistic Annotated Bibliography (LAB) as a searchable
      Web portal to quickly and easily access reliable database norms, related
      programs, and variable calculations. These publications were coded by language,
      number of stimuli, stimuli type (i.e., words, pictures, symbols), keywords (i.e.,
      frequency, semantics, valence), and other useful information. This tool not only
      allows researchers to search for the specific type of stimuli needed for
      experiments but also permits the exploration of publication trends across 100
      years of research. Details about the portal creation and use are outlined, as
      well as various analyses of change in publication rates and keywords. In general,
      advances in computational power have allowed for the increase in dataset size in
      the recent decades, in addition to an increase in the number of linguistic
      variables provided in each publication.

PMID- 30284212
TI  - Beyond frequency counts: Novel conceptual recurrence analysis metrics to index
      semantic coordination in team communications.
AB  - Semantic alignment is a key process underlying interpersonal and team
      communication. However, semantic similarity is difficult to quantify, and
      statistical approaches designed to measure it often rely on methods that make the
      identification of the relative importance of key words difficult. This study
      outlines how conceptual recurrence analysis (CRA) can address these issues and
      can be used to detect conceptual structure in interpersonal communication. We
      developed several novel CRA metrics to analyze communication data reported
      previously by Mancuso, Finomore, Rahill, Blair, and Funke (Proceedings of the
      Human Factors and Ergonomics Society Annual Meeting, 58, 405-409, 2014), gathered
      from teams who worked cooperatively on a logic puzzle under different cognitive
      biasing contexts. CRA, like other measures of semantic coordination, relies on
      parameters whose values affect estimates of semantic alignment. We evaluated how
      the dimensionality of semantic spaces affects metrics quantifying the conceptual
      similarity of communicative exchanges, and whether metrics calculated from top
      down, a priori semantic spaces or bottom-up semantic spaces empirically derived
      from each data set were more sensitive to biasing context. We found that the
      novel CRA measures were sensitive to manipulations of cognitive bias, and that
      higher-dimensional, bottom-up semantic spaces generally yielded more sensitivity
      to the experimental manipulations, though when the communication was evaluated
      with respect to specific key concepts, lower-dimensional, top-down spaces
      performed nearly as well. We conclude that CRA is sensitive to experimental
      manipulations in ways consistent with prior findings and that it presents a
      customizable framework for testing predictions about interpersonal communication
      patterns and other linguistic exchanges.

PMID- 30284213
TI  - Remote associates test: An empirical proof of concept.
AB  - Associative processes play a major role in research on human thinking, especially
      creativity. One of the most influential models emphasizing associative processes
      in creative thinking was introduced by Mednick (Psychological Review, 69, 220
      232, 1962), who developed the remote associates test (RAT) as a domain-general
      measure of individual differences in associative hierarchies. Although S.
      Mednick's theoretical framework has recently regained much attention, the
      fundamental psychometric assumptions and underlying cognitive processes involved
      in the RAT remain controversial. We carried out two studies to evaluate these
      issues. In the first, a confirmatory factor analysis showed that a single latent
      factor accounted for the ability to solve RAT problems, despite their
      psycholinguistic heterogeneity. Subsequent regression analyses indicated that cue
      solution associative remoteness substantially determined the difficulty of RAT
      problems, accounting for about 80% of variance. In the second study we used a
      newly developed associative chain test (ACT), which assesses lexical-semantic and
      executive measures during associative processing. We found that performance on
      the RAT was related to lexical-semantic (higher response remoteness and lower
      response commonness) but not to executive (response inhibition and switching) ACT
      measures. Overall, our findings indicate that the RAT reflects a coherent ability
      to access and combine remote elements in lexical-semantic and associative
      networks without considerably engaging executive attention. Although the validity
      and utility of the RAT was supported, we propose that the ACT provides a more
      complex and fine-grained tool for the assessment of associative processing.

PMID- 30284214
TI  - Pharmacoepidemiologic Evaluation of Birth Defects from Health-Related Postings in
      Social Media During Pregnancy.
AB  - INTRODUCTION: Adverse effects of medications taken during pregnancy are
      traditionally studied through post-marketing pregnancy registries, which have
      limitations. Social media data may be an alternative data source for pregnancy
      surveillance studies. OBJECTIVE: The objective of this study was to assess the
      feasibility of using social media data as an alternative source for pregnancy
      surveillance for regulatory decision making. METHODS: We created an automated
      method to identify Twitter accounts of pregnant women. We identified 196 pregnant
      women with a mention of a birth defect in relation to their baby and 196 without
      a mention of a birth defect in relation to their baby. We extracted information
      on pregnancy and maternal demographics, medication intake and timing, and birth
      defects. RESULTS: Although often incomplete, we extracted data for the majority
      of the pregnancies. Among women that reported birth defects, 35% reported taking
      one or more medications during pregnancy compared with 17% of controls. After
      accounting for age, race, and place of residence, a higher medication intake was
      observed in women who reported birth defects. The rate of birth defects in the
      pregnancy cohort was lower (0.44%) compared with the rate in the general
      population (3%). CONCLUSIONS: Twitter data capture information on medication
      intake and birth defects; however, the information obtained cannot replace
      pregnancy registries at this time. Development of improved methods to
      automatically extract and annotate social media data may increase their value to
      support regulatory decision making regarding pregnancy outcomes in women using
      medications during their pregnancies.

PMID- 30284215
TI  - Surveillance of Drug Safety During Pregnancy: Insight in Current International
      Activities, Future Intentions and Need for Support of National Pharmacovigilance
      Centres.
AB  - INTRODUCTION: Surveillance of drug safety during pregnancy is a special interest
      of pharmacovigilance (PV). The role that national PV centres take in this field
      is, however, unclear. AIM: The aim of this study was to provide insight into
      current activities, future intentions and need for support of national PV centres
      in the field of drug safety during pregnancy. METHOD: A web-based questionnaire
      was used to ask PV centres about their current activities concerning the
      surveillance of drug safety during pregnancy, their intentions to implement or
      improve activities and need for support. For these three main topics, questions
      were posed about spontaneous adverse drug reaction (ADR) reporting, additional
      activities to obtain information, signal detection and informing healthcare
      professionals and the public. RESULTS: The questionnaire was sent to PV centres
      of 172 countries. Response was 40%. In general, the PV centres received limited
      numbers of reports of ADRs in the (unborn) child, related to drug exposure during
      pregnancy. Signal detection in pregnancy cases is carried out by 8 out of 58 PV
      centres (13.5%). Most PV centres mention they have intentions to implement or
      improve activities, mainly for spontaneous reporting (69.4%) and methods for
      signal detection (67.2%). Support was needed for all topics of the questionnaire.
      CONCLUSION: Current activities of national PV centres concerning drug safety
      during pregnancy are limited. The majority of PV centres are, however, willing to
      improve or implement activities. Programmes should be set up in order to support
      and stimulate PV centres with these activities. The aim of all these activities
      is to increase knowledge about the safety of drugs during pregnancy.

PMID- 30284216
TI  - Psychometric properties of the Spanish version of the Experience of Caregiving
      Inventory (ECI) among caregivers of individuals with an eating disorder.
AB  - PURPOSE: The aim of this study was to examine the psychometric properties of the
      Spanish version of the Experience of Caregiving Inventory (ECI-S), which is
      designed to assess the caregiver's appraisal of the impact of caring for a
      relative with a serious mental illness. METHODS: A cross-sectional study was
      conducted among 320 caregivers of a relative with an eating disorder to examine:
      (a) descriptive statistics; (b) internal consistency reliability; (c) the fit of
      the original ten-factor structure of the ECI through exploratory factor analysis,
      using a semi-confirmatory approach, for each subscale individually, and (d)
      concurrent validity. A total of 307 caregivers completed the scale. RESULTS:
      Reliability of the ECI subscales scores was acceptable (alpha = 0.63-0.89).
      Results replicated the original ten-factor structure of the instrument. The
      concurrent validity was supported by correlations of the ECI-negative subscale
      with psychological distress (GHQ-12, 0.43), and with depression and anxiety
      (HADS, 0.48 and 0.49, respectively). CONCLUSIONS: The Spanish version of the ECI
      (ECI-S) demonstrated good psychometric properties in terms of validity and
      reliability that were similar to the original version. It is an acceptable and
      valid instrument for assessing the impact on family members of caring for a
      relative with an eating disorder and can be recommended for use in clinical
      settings in Spain. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

PMID- 30284217
TI  - Italian Society of Obesity IX National Congress : Milan, 11-13 October.

PMID- 30284218
TI  - 18th ISoP Annual Meeting "Pharmacovigilance without borders" Geneva, Switzerland,
      11-14 November, 2018.

PMID- 30284219
TI  - Exophthalmos or pseudo-exophthalmos in the Last Judgement (1535-1541) by
      Michelangelo Buonarroti (1475-1564).

PMID- 30284220
TI  - Effects of metabolic abnormalities, hyperandrogenemia and clomiphene on liver
      function parameters among Chinese women with polycystic ovary syndrome: results
      from a randomized controlled trial.
AB  - PURPOSE: To investigate the effects of metabolic abnormalities, hyperandrogenemia
      and ovulation induction by clomiphene/acupuncture on liver function parameters
      among women with polycystic ovary syndrome (PCOS). METHODS: This is a secondary
      analysis of a randomized controlled trial. All 1000 subjects were diagnosed as
      PCOS by modified Rotterdam criteria. Liver function parameters, metabolic panel
      and hormone profile were measured at baseline and after treatment. The
      relationship between liver parameters with metabolic, hormonal parameters and
      ovulation induction was examined. RESULTS: PCOS women with metabolic syndrome had
      higher liver enzyme levels but lower bilirubin and bile acid levels than without.
      PCOS women with hyperandrogenemia had higher liver enzyme, bilirubin levels than
      without. Correlation analyses showed that worsening of metabolic parameters was
      associated with higher liver enzyme levels but lower bilirubin and bile acid
      levels, while increased androgen levels were associated with higher liver enzyme,
      bilirubin and bile acid levels. Ovulation induction with clomiphene citrate could
      decrease bilirubin and bile acid levels, while acupuncture had no obvious effect
      on liver function. CONCLUSIONS: Among PCOS women, metabolic abnormalities and
      hyperandrogenemia impaired different liver function parameters. Clomiphene could
      decrease the bilirubin and bile acid levels while acupuncture had no obvious
      effect on liver function.

PMID- 30284223
TI  - Quantitative proteomics analysis of sporadic parathyroid adenoma tissue samples.
AB  - OBJECTIVE: Molecular pathogenesis of parathyroid tumors is incompletely
      understood. Identification of novel molecules and understanding their role in
      parathyroid tumorigenesis by proteomics approach would be informative with
      potential clinical implications. METHOD: Adenomatous (n = 5) and normal (n = 2)
      parathyroid tissue lysates were analyzed for protein profile by LC-MS/MS method
      and the proteins were classified using bioinformatics tools such as PANTHER and
      toppfun functional enrichment tool. Identified proteins were further validated by
      western blotting and qRT-PCR (n = 20). RESULT: Comparative proteomics analysis
      revealed that a total of 206 proteins (74 upregulated and 132 downregulated) were
      differentially expressed (>= twofold change) in adenomas. Bioinformatics analysis
      revealed that 48 proteins were associated with plasma membrane, 49 with
      macromolecular complex, 39 were cytoplasm, 38 were organelle related, 21 were
      cell junction and 10 were extracellular proteins. These proteins belonged to a
      diverse protein family such as enzymes, transcription factors, cell signalling,
      cell adhesion, cytoskeleton proteins, receptors, and calcium-binding proteins.
      The major biological processes predicted for the proteins were a cellular,
      metabolic and developmental process, cellular localization, and biological
      regulation. The differentially expressed proteins were found to be associated
      with MAPK, phospholipase C (PLC) and phosphatidylinositol (PI) signalling
      pathways, and with chromatin organization. Western blot and qRT-PCR analysis of
      three proteins (DNAJC2, ACO2, and PRDX2) validated the LC-MS/MS findings.
      CONCLUSION: This exploratory study demonstrates the feasibility of proteomics
      approach in finding the dysregulated proteins in benign parathyroid adenomas, and
      our preliminary results suggest that MAPK, PLC and PI signalling pathways and
      chromatin organization are involved in parathyroid tumorigenesis.

PMID- 30284224
TI  - Fasting glucagon-like peptide 1 concentration is associated with lower
      carbohydrate intake and increases with overeating.
AB  - PURPOSE: Glucagon-like peptide 1 (GLP-1) is an incretin hormone that appears to
      play a major role in the control of food intake. The aim of this investigation
      was to evaluate and quantify the association of circulating GLP-1 concentration
      with ad libitum total calorie and macronutrient intake. METHODS: One-hundred and
      fifteen individuals (72 men) aged 35 +/- 10 years were admitted for an inpatient
      study investigating the determinants of energy intake. Ad libitum food intake was
      assessed during 3 days using a reproducible vending machine paradigm. Fasting
      plasma GLP-1 concentrations were measured on the morning of the first day and on
      the morning of the fourth day after ad libitum feeding. RESULTS: Plasma GLP-1
      concentrations increased by 14% after 3 days of ad libitum food intake.
      Individuals overate on average 139 +/- 45% of weight-maintaining energy needs.
      Fasting plasma GLP-1 on day 1 was negatively associated with carbohydrate intake
      (r = - 0.2, p = 0.03) and with daily energy intake from low fat-high simple sugar
      (r = - 0.22, p = 0.016). CONCLUSION: Higher plasma GLP-1 concentrations prior to
      ad libitum food intake were associated with lower carbohydrate intake and lower
      simple sugar ingestion, indicating a possible role of the GLP-1 in the reward
      pathway regulating simple sugar intake. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT00342732.

PMID- 30284222
TI  - Genome-wide association analysis suggests novel loci for Hashimoto's thyroiditis.
AB  - PURPOSE: Hashimoto's thyroiditis (HT) is the most common form of autoimmune
      thyroid diseases. Current knowledge of HT genetics is limited, and not a single
      genome-wide association study (GWAS) focusing exclusively on HT has been
      performed to date. In order to decipher genetic determinants of HT, we performed
      the first GWAS followed by replication in a total of 1443 individuals from
      Croatia. METHODS: We performed association analysis in a discovery cohort
      comprising 405 cases and 433 controls. We followed up 13 independent signals (P <
      10-5) in 303 cases and 302 controls from two replication cohorts and then meta
      analyzed results across discovery and replication datasets. RESULTS: We
      identified three variants suggestively associated with HT: rs12944194 located 206
      kb from SDK2 (P = 1.8 * 10-6), rs75201096 inside GNA14 (P = 2.41 * 10-5) and
      rs791903 inside IP6K3 (P = 3.16 * 10-5). Genetic risk score (GRS), calculated
      using risk alleles of these loci, accounted for 4.82% of the total HT variance,
      and individuals from the top GRS quartile had 2.76 times higher odds for HT than
      individuals from the lowest GRS quartile. CONCLUSIONS: Although discovered loci
      are implicated with susceptibility to HT for the first time, genomic regions
      harboring these loci exhibit good biological candidacy due to involvement in the
      regulation of the thyroid function and autoimmunity. Additionally, we observe
      genetic overlap between HT and several related traits, such as hypothyroidism,
      Graves' disease and TPOAb. Our study adds a new knowledge of underlying HT
      genetics and sets a firm basis for further research.

PMID- 30284221
TI  - Treating varicocele in 2018: current knowledge and treatment options.
AB  - PURPOSE: Varicocele is defined as a state of varicosity and tortuosity of the
      pampiniform plexus around the testis caused by retrograde blood flow through the
      internal spermatic vein. The prevalence of clinically relevant varicocele ranges
      from 5 to 20% in the male population and is often associated with infertility and
      reduction of sperm quality. In this review, the pathophysiology and clinical
      aspects of varicocele are reviewed along with therapeutic options and treatment
      effects on sperm parameters and fertility both in adult and in
      pediatric/adolescent subjects. METHODS: We conducted a Medline and a PubMed
      search from 1965 to 2018 to identify publications related to varicocele clinical
      aspects, treatment procedures and treatment outcomes. Keywords used for the
      search were: "varicocele", "varicocelectomy", "sclerotherapy", "male
      infertility", "subfertility", and "semen abnormalities". RESULTS: Data from a
      large number of studies in adolescent and adult males indicate that varicocele
      correction improves semen parameters in the majority of patients, reducing
      oxidative stress and improving sperm nuclear DNA integrity either with surgical
      or percutaneous approach. CONCLUSIONS: Varicocele repair seems to represent a
      cost-effective therapeutic option for all males (both adolescent and adults) with
      a clinical varicocele in the presence of testicular hypotrophy, worsening sperm
      alterations or infertility. On the other hand, some investigators questioned the
      role of varicocelectomy in the era of assisted reproduction. Thus, a better
      understanding of the pathophysiology of varicocele-associated male subfertility
      is of paramount importance to elucidating the deleterious effects of varicocele
      on spermatogenesis and possibly formulating new treatment strategies.

PMID- 30284225
TI  - Leptin Signaling in the Control of Metabolism and Appetite: Lessons from Animal
      Models.
AB  - Obesity has become a major health concern in modern times, as it significantly
      increases the risk for the development of cardiovascular diseases, type 2
      diabetes mellitus, and some types of cancer. The obesity epidemic has brought
      considerable attention to the molecular mechanisms through which adipocyte
      secreted adipokines regulate physiological processes involved in metabolic and
      inflammatory diseases. Among them, leptin is considered as one of the principal
      regulators of a variety of physiological processes, including appetite and energy
      metabolism, through its binding to a variety of receptors and in particular by
      signaling through the long isoform receptor ObRb. Leptin signaling in the brain
      via ObRb plays an important role in the regulation of appetite and food intake,
      and involves several signaling pathways that either upregulate or attenuate
      leptin's anorexigenic response. This review describes ObRb-dependent, leptin
      induced signaling pathways implicated in the control of appetite and energy
      metabolism in the organism, based on current information from animal models.

PMID- 30284226
TI  - Role of Cerium Oxide Nanoparticles in a Paraquat-Induced Model of Oxidative
      Stress: Emergence of Neuroprotective Results in the Brain.
AB  - Paraquat (PQ), as a widely used herbicide, enhances the formation of free
      radicals and oxidative stress. Cerium oxide nanoparticles (CeNPs) are one of the
      most utilized and effective nanoparticles having strong antioxidative properties
      and inhibiting free radicals. Here, we aimed to investigate the effects of CeNPs
      on brain oxidative toxic stress injury induced with PQ. The male rats were
      treated intraperitoneally daily with PQ (50 mg/kg/day) and CeNPs (15, 30, and 60
      mg/kg/day) alone or in combination for 2 weeks. After treatments, the brain
      tissue samples were collected. Oxidative toxic stress biomarkers including lipid
      peroxidation (LPO), total antioxidant capacity (TAC), and total thiol molecules
      (TTM) as well as DNA damage and caspase-3 levels were measured. Moreover, the
      mRNA expression levels of Nestin and Neurod1 were assayed. Our results showed
      that PQ has significantly increased brain LPO, DNA damage, and caspase-3 levels
      and further reduced TAC and TTM contents, as well as expression levels of Nestin
      and Neurod1, compared with the control group (injection of saline). CeNPs (15-
      and 30-mg/kg doses) in groups co-administered with PQ significantly ameliorated
      the LPO, DNA damage, and caspase-3 levels while increasing TAC and TTM contents
      as well as enhancing Nestin and Neurod1 mRNA expression levels in the brain
      samples (P < 0.05). These findings suggest a neuroprotective and antioxidant role
      for CeNPs in PQ-induced brain injury. However, further studies are required to
      clarify its clinical/pharmacological significance.

PMID- 30284228
TI  - OIP5 Expression Sensitize Glioblastoma Cells to Lomustine Treatment.
AB  - Glioblastoma (GBM) is an incurable disease ranked among the deadliest solid
      cancers worldwide. A better understanding on the molecular aspects of this
      malignancy could contribute to the development of new treatment strategies and
      help to improve survival rates. Previously, our group had shown that GBM patients
      expressing the cancer/testis antigen Opa Interacting Protein 5 (OIP5) present a
      longer survival period than the OIP5-negative group. The main goal of this study
      was to evaluate the OIP5 contribution to GBM tumorigenesis and assess the role of
      OIP5 in GBM cell response to lomustine, an alkylating agent used in the treatment
      of this malignancy. So, the effect of OIP5 knockdown was evaluated in A172 and
      T98G GBM cell lines. Our results demonstrated that downregulation of the OIP5
      stimulates glioma cell viability and inhibits cell death-induced necrosis
      prompted by lomustine. In conclusion, our data shows that OIP5 expression in GBM
      cells seems to be able to enhance lomustine cytotoxic effects, reinforcing that
      this gene is a potential therapeutic target and putative molecular biomarker for
      treatment response in GBM.

PMID- 30284227
TI  - Quinolinic Acid-Induced Huntington Disease-Like Symptoms Mitigated by Potent Free
      Radical Scavenger Edaravone-a Pilot Study on Neurobehavioral, Biochemical, and
      Histological Approach in Male Wistar Rats.
AB  - In this study, we demonstrated for the first time the neuroprotective role of
      edaravone (Eda) (5 and 10 mg/kg b.w.), a potent free radical scavenger against
      the unilateral stereotaxic induction of quinolinic acid (QA) (300 nm/4 MUl
      saline)-induced Huntington disease (HD)-like symptoms in behavioral, biochemical,
      and histological features in male Wistar rats striatum. QA induction, which
      mimics the early stage of HD, commonly causes oxidative stress to the cell and
      decreases the antioxidant defense mechanism by altering the level of lipid
      peroxidation (LPO), protein carbonyls, and nitrate concentration (NO) and the
      activities of glutathione family enzymes (GPx, GST, GR) and acetyl choline
      esterase concentration (AChE) which was found to be ameliorated by Eda treatment
      in both the tested doses 5 and 10 mg/kg b.w. in the significance of P < 0.05 and
      P < 0.01, respectively. Finally histopathological analysis by hematoxylin and
      eosin stain concluded the promising neurodefensive role of Eda in rat striatum at
      the dosage of 10 mg/kg b.w., with the decreased tissue damage and the number of
      damaged granular cells when compared to QA-induced groups.

PMID- 30284229
TI  - The Independent and Combined Effects of Omega-3 and Vitamin B12 in Ameliorating
      Propionic Acid Induced Biochemical Features in Juvenile Rats as Rodent Model of
      Autism.
AB  - Metabolites of proper fatty acids modulate the inflammatory response and are
      essential for normal brain development; equally, abnormal fatty acid metabolism
      plays a critical role in the pathology of autism. Currently, dietary supplements
      are often used to improve the core symptoms of Autism spectrum disorder (ASD).
      The present study analyzed the effects of orally supplemented omega-3 (omega-3)
      and vitamin B12 on ameliorating oxidative stress and impaired lipid metabolism in
      a propionic acid (PPA)-induced rodent model of autism, together with their effect
      on the gut microbial composition, where great fluctuations in the bacterial
      number and strains were observed; interestingly, polyunsaturated fatty acids such
      as omega-3 induced higher growth of the gram-positive bacterium Staphylococcus
      aureus and decreased the survival rates of Clostridia sp. as well as other
      enteric bacterial strains. Thirty-five young male western albino rats were
      divided into five equal groups. The first group served as the control; the second
      group was given an oral neurotoxic dose of PPA (250 mg/kg body weight/day) for 3
      days. The third group received an oral dose of omega-3 (200 mg/kg body
      weight/day) for 30 days after the 3-day PPA treatment. Group four was given an
      oral dose of vitamin B12 (16.7 mg/kg/day) for 30 days after PPA treatment.
      Finally, group five was given a combination of both omega-3 and vitamin B12 at
      the same dose for the same duration after PPA treatment. Biochemical parameters
      related to oxidative stress and impaired fatty acid metabolism were investigated
      in the brain homogenates of each group. The effects of the dietary supplements on
      the gut microbiota were also observed. The PPA-treated autistic model expressed
      significantly higher levels of lipid peroxides and 5-lipoxygenase (5-LOX) and
      significantly less glutathione (GSH), glutathione S-transferase (GST), and
      cyclooxygenase 2 (COX2) than the control group. However, a remarkable
      amelioration of most of the impaired markers was observed with oral
      supplementation with omega-3 and vitamin B12, either alone or in combination. Our
      results concluded that impairment at various steps of the lipid metabolic
      pathways may contribute to the development of autism; however, supplementation
      with omega-3 and vitamin B12 can result in a positive therapeutic effect.

PMID- 30284230
TI  - Hydrogen peroxide-induced mitophagy contributes to laryngeal cancer cells
      survival via the upregulation of FUNDC1.
AB  - PURPOSE: The purpose of our study was to investigate an underlying mechanism that
      hydrogen peroxide-induced mitophagy contributed to laryngeal cancer cells
      survivals under oxidative stress condition. METHODS: Tumor tissue and serum
      samples were collected from patients with laryngeal cancer. The Hep2 cell, a
      human laryngeal carcinoma cell, was used in in vitro experiments. The levels of
      lipid peroxidation were analyzed by ELISA. Knockdown of FUNDC1 was performed by
      RNAi. The changes of target proteins were determined by qRT-PCR and western blot.
      The cells were analyzed for changes in proliferation using cell counting kit-8
      and mitophagy by the mitochondrial membrane potential assay and transmission
      electron microscopy. RESULTS: FUNDC1 in laryngeal cancer tissues were relative to
      the levels of lipid peroxidation in laryngeal cancer patients, which suggested
      that FUNDC1 was associated with the status of oxidative stress in the laryngeal
      cancer patients. Hydrogen peroxide significantly induced the elevation of FUNDC1,
      a mitophagic factor, in a time- and dose-dependent manner in laryngeal cancer
      cells, which was dependent on ERK signal activation. Knockdown of FUNDC1 by the
      siRNA attenuated the survival of laryngeal cancer cells under hydrogen peroxide
      stimulation. Moreover, the elevated FUNDC1 was required for the occurrence of
      mitophagy under hydrogen peroxide stimulation, which was identified by
      transmission electron microscopy, the alterations of mitochondrial permeability
      transition and the specific mitochondrial protein, hsp60. Inhibition of mitophagy
      with cyclosporine A could also effectively attenuate the laryngeal cancer cells
      survival under hydrogen peroxide stimulation. CONCLUSIONS: Hydrogen peroxide
      upregulated the expression of FUNDC1 through the activation of ERK1/2 signal to
      trigger a mitophagic response, giving laryngeal cancer cells a befit for
      survival. These findings suggested that FUNDC1 might be a potential target for
      the treatment of laryngeal cancer accompanied with high lipid peroxidation
      status.

PMID- 30284231
TI  - Correction to: Efficacy of fulvestrant in the treatment of postmenopausal women
      with endocrine-resistant advanced breast cancer in routine clinical practice.
AB  - A sentence under 'Results' heading in the Abstract section was published
      incorrectly. The correct sentence should read as follows.

PMID- 30284232
TI  - Clinical management of cutaneous adverse events in patients on targeted
      anticancer therapies and immunotherapies: a national consensus statement by the
      Spanish Academy of Dermatology and Venereology and the Spanish Society of Medical
      Oncology.
AB  - Progress in the understanding of many tumors has enabled the development of new
      therapies, such as those targeted at specific molecules involved in cell growth
      (targeted therapies) or intended to modulate the immune system (immunotherapy).
      However, along with the clinical benefit provided by these new treatments, new
      adverse effects have also appeared. Dermatological toxicities such as
      papulopustular eruptions, xerosis, and pruritus are common with EGFR inhibitors.
      Other adverse effects have also been described with PDGFR, BCR-ABL, and MAPK
      tyrosine kinase inhibitors, antiangiogenic drugs, and inhibitors at immune
      checkpoints such as CTLA-4 and PD-1/PD-L1. Onset of these adverse effects often
      causes dose reductions and/or delays in administering the prescribed therapy,
      which can affect patient survival and quality of life. It is, therefore,
      important to prevent the occurrence of these adverse effects, or to treat
      unavoidable ones as soon as possible. This requires cooperation between medical
      oncologists and dermatologists. This article reviews the various dermatological
      toxicities associated with targeted therapies and immunotherapies, along with
      their diagnosis and therapeutic management.

PMID- 30284233
TI  - Re-irradiation of recurrent glioblastoma as part of a sequential multimodality
      treatment concept.
AB  - PURPOSE: The aim of this retrospective study was to evaluate survival outcomes in
      well-performing, mainly, young patients receiving a sequence of all available
      therapeutic options for relapsed glioblastoma, including re-irradiation. METHODS:
      We performed a retrospective analysis of 27 patients irradiated twice for
      glioblastoma between 2008 and 2016. In the first line, all had surgical treatment
      of the tumor followed by radiotherapy with a total dose of 60 Gy and
      temozolomide. All re-irradiated patients were treated with a total dose of 36 Gy
      in 12 fractions. The endpoints were death from glioblastoma or any cause, and
      toxicity after re-irradiation. RESULTS: The median follow-up of survivors was
      35.6 months. At the time of analysis, 25 patients had died. The median time
      between first and second radiotherapy was 18.9 months (6.1-58.4). Re-irradiation
      was performed at different time points of first, second and third progression.
      The median overall survival after first diagnosis was 39.2 months. Five years
      after first surgery, nearly 20% of the patients were alive. CONCLUSION: Carefully
      planned re-irradiation of the brain is a safe therapy for recurrent glioblastoma.
      Younger and well-performing patients benefit from all available therapy options.
      Every patient should be discussed in a multidisciplinary setting at each time
      point of tumor progression. Further prospective studies are needed to define the
      optimal time, dose and volume of re-irradiation.

PMID- 30284235
TI  - Subjective sleep impairment and affective symptoms in frail elderly.

PMID- 30284236
TI  - Suicide in the elderly: an underappreciated and understudied issue.

PMID- 30284234
TI  - Risk of malnutrition and emotional distress as factors affecting health-related
      quality of life in patients with resected cancer.
AB  - INTRODUCTION: This study analyzes the prevalence of malnutrition, depression,
      anxiety, and somatization and which factor has the biggest effect on quality of
      life (QoL) in individuals with resected cancer. METHODS: A prospective study was
      conducted among 747 participants. Participants completed the EORTC-QLQ30, MST,
      and BSI-18 questionnaires. RESULTS: Prevalence for risk of malnutrition,
      depression, anxiety, and somatization were 36.4%, 35.5%, 35.2%, and 48.8%,
      respectively. Hierarchical multiple regression analyses revealed that
      malnutrition risk, somatization, depression, and anxiety accounted for 50.8% of
      the variance in functional scale, 45.3% in symptom scale, and 52.2% in global
      health. Malnutrition, somatization, depression, and anxiety displayed high
      explanatory power on all health-related QoL (HRQoL) scales. CONCLUSION: The risk
      of malnutrition and psychological symptoms is strongly associated with HRQoL in
      cancer patients; thus, medical oncologists should develop effective interventions
      that contribute to lowering the risk of malnutrition and psychological distress,
      thereby improving subjects' HRQoL before initiating adjuvant chemotherapy.

PMID- 30284238
TI  - Apolipoprotein E gene polymorphisms: a risk factor for preterm brain injury?

PMID- 30284237
TI  - Medication adherence, costs, and ER visits of nurse practitioner and primary care
      physician patients: Evidence from three cohorts of Medicare beneficiaries.
AB  - OBJECTIVE: To compare medication adherence, cost, and utilization in Medicare
      beneficiaries attributed to nurse practitioners (NP) and primary care physicians
      (PCP). DATA: Medicare Part A, B, and D claims and beneficiary summary file data,
      years 2009-2013. STUDY DESIGN: We used propensity score-weighted analyses
      combined with logistic regression and generalized estimating equations to test
      differences in good medication adherence (proportion of days covered (PDC >0.8);
      office-based and specialty care costs; and ER visits. DATA EXTRACTION:
      Beneficiaries with prescription claims for anti-diabetics, renin-angiotensin
      system antagonists (RASA), or statins. PRINCIPAL FINDINGS: There were no
      differences in good medication adherence (PDC >0.8) between NP and PCP attributed
      beneficiaries taking anti-diabetics or RASA. Beneficiaries taking statins had a
      slightly higher probability of good adherence when attributed to PCPs (74.6% vs
      75.5%; P < 0.05). NP attributed beneficiaries had lower office-based and
      specialty care costs and were less likely to experience an ER visit across all
      three medication cohorts (P < 0.01). CONCLUSIONS: Examining the impact of NP and
      PCP provided care on outcomes beyond the primary care setting is important to the
      Medicare program in general but will also help practices seeking to meet
      benchmarks under alternative payment models that incentivize higher quality and
      lower costs.

PMID- 30284239
TI  - Preoperative radiotherapy and curative surgery for the management of localised
      rectal carcinoma.
AB  - BACKGROUND: This is an update of the original review published in 2007.Carcinoma
      of the rectum is a common malignancy, especially in high income countries. Local
      recurrence may occur after surgery alone. Preoperative radiotherapy (PRT) has the
      potential to reduce the risk of local recurrence and improve outcomes in rectal
      cancer. OBJECTIVES: To determine the effect of preoperative radiotherapy for
      people with localised resectable rectal cancer compared to surgery alone. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL)
      (the Cochrane Library; Issue 5, 2018) (4 June 2018), MEDLINE (Ovid) (1950 to 4
      June 2018), and Embase (Ovid) (1974 to 4 June 2018). We also searched
      ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform
      (ICTRP) for relevant ongoing trials (4 June 2018). SELECTION CRITERIA: We
      included randomised controlled trials comparing PRT and surgery with surgery
      alone for people with localised advanced rectal cancer planned for radical
      surgery. We excluded trials that did not use contemporary radiotherapy techniques
      (with more than two fields to the pelvis). DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed the 'Risk of bias' domains for each
      included trial, and extracted data. For time-to-event data, we calculated the
      Peto odds ratio (Peto OR) and variances, and for dichotomous data we calculated
      risk ratios (RR) using the random-effects method. Potential sources of
      heterogeneity hypothesised a priori included study quality, staging, and the use
      of total mesorectal excision (TME) surgery. MAIN RESULTS: We included four trials
      with a total of 4663 participants. All four trials reported short PRT courses,
      with three trials using 25 Gy in five fractions, and one trial using 20 Gy in
      four fractions. Only one study specifically required TME surgery for inclusion,
      whereas in another study 90% of participants received TME surgery.Preoperative
      radiotherapy probably reduces overall mortality at 4 to 12 years' follow-up (4
      trials, 4663 participants; Peto OR 0.90, 95% CI 0.83 to 0.98; moderate-quality
      evidence). For every 1000 people who undergo surgery alone, 454 would die
      compared with 45 fewer (the true effect may lie between 77 fewer to 9 fewer) in
      the PRT group. There was some evidence from subgroup analyses that in trials
      using TME no or little effect of PRT on survival (P = 0.03 for the difference
      between subgroups).Preoperative radiotherapy may have little or no effect in
      reducing cause-specific mortality for rectal cancer (2 trials, 2145 participants;
      Peto OR 0.89, 95% CI 0.77 to 1.03; low-quality evidence).We found moderate
      quality evidence that PRT reduces local recurrence (4 trials, 4663 participants;
      Peto OR 0.48, 95% CI 0.40 to 0.57). In absolute terms, 161 out of 1000 patients
      receiving surgery alone would experience local recurrence compared with 83 fewer
      with PRT. The results were consistent in TME and non-TME studies.There may be
      little or no difference in curative resection (4 trials, 4673 participants; RR
      1.00, 95% CI 0.97 to 1.02; low-quality evidence) or in the need for sphincter
      sparing surgery (3 trials, 4379 participants; RR 0.99, 95% CI 0.94 to 1.04; I2 =
      0%; low-quality evidence) between PRT and surgery alone.Low-quality evidence
      suggests that PRT may increase the risk of sepsis from 13% to 16% (2 trials, 2698
      participants; RR 1.25, 95% CI 1.04 to 1.52) and surgical complications from 25%
      to 30% (2 trials, 2698 participants; RR 1.20, 95% CI 1.01 to 1.42) compared to
      surgery alone.Two trials evaluated quality of life using different scales. Both
      studies concluded that sexual dysfunction occurred more in the PRT group. Mixed
      results were found for faecal incontinence, and irradiated participants tended to
      resume work later than non-irradiated participants between 6 and 12 months, but
      this effect had attenuated after 18 months (low-quality evidence). AUTHORS'
      CONCLUSIONS: We found moderate-quality evidence that PRT reduces overall
      mortality. Subgroup analysis did not confirm this effect in people undergoing TME
      surgery. We found consistent evidence that PRT reduces local recurrence. Risk of
      sepsis and postsurgical complications may be higher with PRT.The main limitation
      of the findings of the present review concerns their applicability. The included
      trials only assessed short-course radiotherapy and did not use chemotherapy,
      which is widely used in the contemporary management of rectal cancer disease. The
      differences between the trials regarding the criteria used to define rectal
      cancer, staging, radiotherapy delivered, the time between radiotherapy and
      surgery, and the use of adjuvant or postoperative therapy did not appear to
      influence the size of effect across the studies.Future trials should focus on
      identifying participants that are most likely to benefit from PRT especially in
      terms of improving local control, sphincter preservation, and overall survival
      while reducing acute and late toxicities (especially rectal and sexual function),
      as well as determining the effect of radiotherapy when chemotherapy is used and
      the optimal timing of surgery following radiotherapy.

PMID- 30284240
TI  - Psychological interventions for needle-related procedural pain and distress in
      children and adolescents.
AB  - BACKGROUND: This is the second update of a Cochrane Review (Issue 4, 2006). Pain
      and distress from needle-related procedures are common during childhood and can
      be reduced through use of psychological interventions (cognitive or behavioral
      strategies, or both). Our first review update (Issue 10, 2013) showed efficacy of
      distraction and hypnosis for needle-related pain and distress in children and
      adolescents. OBJECTIVES: To assess the efficacy of psychological interventions
      for needle-related procedural pain and distress in children and adolescents.
      SEARCH METHODS: We searched six electronic databases for relevant trials:
      Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; PsycINFO;
      Embase; Web of Science (ISI Web of Knowledge); and Cumulative Index to Nursing
      and Allied Health Literature (CINAHL). We sent requests for additional studies to
      pediatric pain and child health electronic listservs. We also searched registries
      for relevant completed trials: clinicaltrials.gov; and World Health Organization
      International Clinical Trials Registry Platform (www.who.int.trialsearch). We
      conducted searches up to September 2017 to identify records published since the
      last review update in 2013. SELECTION CRITERIA: We included peer-reviewed
      published randomized controlled trials (RCTs) with at least five participants per
      study arm, comparing a psychological intervention with a control or comparison
      group. Trials involved children aged two to 19 years undergoing any needle
      related medical procedure. DATA COLLECTION AND ANALYSIS: Two review authors
      extracted data and assessed risks of bias using the Cochrane 'Risk of bias' tool.
      We examined pain and distress assessed by child self-report, observer global
      report, and behavioral measurement (primary outcomes). We also examined any
      reported physiological outcomes and adverse events (secondary outcomes). We used
      meta-analysis to assess the efficacy of identified psychological interventions
      relative to a comparator (i.e. no treatment, other active treatment, treatment as
      usual, or waitlist) for each outcome separately. We used Review Manager 5
      software to compute standardized mean differences (SMDs) with 95% confidence
      intervals (CIs), and GRADE to assess the quality of the evidence. MAIN RESULTS:
      We included 59 trials (20 new for this update) with 5550 participants. Needle
      procedures primarily included venipuncture, intravenous insertion, and vaccine
      injections. Studies included children aged two to 19 years, with few trials
      focused on adolescents. The most common psychological interventions were
      distraction (n = 32), combined cognitive behavioral therapy (CBT; n = 18), and
      hypnosis (n = 8). Preparation/information (n = 4), breathing (n = 4), suggestion
      (n = 3), and memory alteration (n = 1) were also included. Control groups were
      often 'standard care', which varied across studies. Across all studies, 'Risk of
      bias' scores indicated several domains at high or unclear risk, most notably
      allocation concealment, blinding of participants and outcome assessment, and
      selective reporting. We downgraded the quality of evidence largely due to serious
      study limitations, inconsistency, and imprecision.Very low- to low-quality
      evidence supported the efficacy of distraction for self-reported pain (n = 30,
      2802 participants; SMD -0.56, 95% CI -0.78 to -0.33) and distress (n = 4, 426
      participants; SMD -0.82, 95% CI -1.45 to -0.18), observer-reported pain (n = 11,
      1512 participants; SMD -0.62, 95% CI -1.00 to -0.23) and distress (n = 5, 1067
      participants; SMD -0.72, 95% CI -1.41 to -0.03), and behavioral distress (n = 7,
      500 participants; SMD -0.44, 95% CI -0.84 to -0.04). Distraction was not
      efficacious for behavioral pain (n = 4, 309 participants; SMD -0.33, 95% CI -0.69
      to 0.03). Very low-quality evidence indicated hypnosis was efficacious for
      reducing self-reported pain (n = 5, 176 participants; SMD -1.40, 95% CI -2.32 to 
      0.48) and distress (n = 5, 176 participants; SMD -2.53, 95% CI -3.93 to -1.12),
      and behavioral distress (n = 6, 193 participants; SMD -1.15, 95% CI -1.76 to 
      0.53), but not behavioral pain (n = 2, 69 participants; SMD -0.38, 95% CI -1.57
      to 0.81). No studies assessed hypnosis for observer-reported pain and only one
      study assessed observer-reported distress. Very low- to low-quality evidence
      supported the efficacy of combined CBT for observer-reported pain (n = 4, 385
      participants; SMD -0.52, 95% CI -0.73 to -0.30) and behavioral distress (n = 11,
      1105 participants; SMD -0.40, 95% CI -0.67 to -0.14), but not self-reported pain
      (n = 14, 1359 participants; SMD -0.27, 95% CI -0.58 to 0.03), self-reported
      distress (n = 6, 234 participants; SMD -0.26, 95% CI -0.56 to 0.04), observer
      reported distress (n = 6, 765 participants; SMD 0.08, 95% CI -0.34 to 0.50), or
      behavioral pain (n = 2, 95 participants; SMD -0.65, 95% CI -2.36 to 1.06). Very
      low-quality evidence showed efficacy of breathing interventions for self-reported
      pain (n = 4, 298 participants; SMD -1.04, 95% CI -1.86 to -0.22), but there were
      too few studies for meta-analysis of other outcomes. Very low-quality evidence
      revealed no effect for preparation/information (n = 4, 313 participants) or
      suggestion (n = 3, 218 participants) for any pain or distress outcome. Given only
      a single trial, we could draw no conclusions about memory alteration. Adverse
      events of respiratory difficulties were only reported in one breathing
      intervention. AUTHORS' CONCLUSIONS: We identified evidence supporting the
      efficacy of distraction, hypnosis, combined CBT, and breathing interventions for
      reducing children's needle-related pain or distress, or both. Support for the
      efficacy of combined CBT and breathing interventions is new from our last review
      update due to the availability of new evidence. The quality of trials and overall
      evidence remains low to very low, underscoring the need for improved
      methodological rigor and trial reporting. Despite low-quality evidence, the
      potential benefits of reduced pain or distress or both support the evidence in
      favor of using these interventions in clinical practice.

PMID- 30284241
TI  - A pilot study of cardiopulmonary exercise testing and cardiac stress positron
      emission tomography before major non-cardiac surgery.
AB  - Cardiac events are a common cause of peri-operative morbidity. Cardiopulmonary
      exercise testing can objectively assess risk, but it does not quantify myocardial
      ischaemia. With appropriate dietary preparation to suppress basal myocardial
      glucose uptake, positron emission tomography with 18 F-fluorodeoxyglucose can
      identify post-ischaemic myocardium, providing an attractive complement to
      exercise testing. We aimed to investigate the feasibility of this diagnostic
      algorithm. Patients referred for cardiopulmonary exercise testing before major
      cancer surgery were prospectively recruited. Exercise testing and positron
      emission tomography imaging were performed after a high fat-low carbohydrate
      meal. Protocol feasibility (primary end-point) included compliance with pre-test
      diet instructions and the completion of tests. Stress myocardial perfusion
      imaging was performed if either exercise testing or positron emission tomography
      was equivocal or positive for ischaemia. We recorded cardiac complications for 30
      postoperative days. We enrolled 26 participants, 20 of whom completed protocol.
      Twenty-one participants proceeded to surgery: myocardial injury or infarction was
      diagnosed in three participants, two of whom had positive or equivocal positron
      emission tomography but negative myocardial perfusion imaging. We have shown that
      pre-operative cardiac positron emission tomography after cardiopulmonary exercise
      testing is feasible; protocol deviations were minor and did not affect image
      quality. Our findings warrant further investigation to compare the diagnostic
      utility of cardiac positron emission tomography imaging with standard pre
      operative stress tests.

PMID- 30284242
TI  - Digest: Hybrid incompatibilities and introgression in wild monkeyflowers.
AB  - How are alleles that are detrimental to fitness maintained in natural
      populations? Zuellig and Sweigart (2018a) find that alleles from a two-locus
      hybrid incompatibility system segregate at considerable frequencies in two
      species of monkeyflowers, suggesting that despite providing a fitness cost, these
      alleles remain polymorphic as a consequence of gene flow between the two species.
      The system provides the potential to understand the evolutionary trajectory of
      hybrid incompatibilities and their role in speciation.

PMID- 30284243
TI  - Regulatory aspects of status epilepticus.
AB  - In this article, we consider four aspects of the regulatory standing of status
      epilepticus and the difficulties these raise in relation to trials and licensing.
      These formed the basis of a discussion held at the 6th London?Innsbruck
      Colloquium on Status Epilepticus, held on April 6, 2017.

PMID- 30284244
TI  - A decade of progress in status epilepticus 2007-2017: Proceedings of the 6th
      London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.

PMID- 30284245
TI  - Preserving the thyroidal isthmus during low tracheostomy with creation of a Bjork
      flap.
AB  - OBJECTIVES/HYPOTHESIS: Surgical tracheostomy (ST) with creation of an inferiorly
      based U-shaped tracheal flap, known as the Bjork flap, is the most commonly
      performed. The purpose of this study was to evaluate whether outcome was
      different in patients who underwent low ST with retraction and preservation of
      the thyroid isthmus compared to those who underwent high ST with ligation of the
      thyroid isthmus. STUDY DESIGN: Retrospective cohort study. METHODS: We included
      1,143 patients who underwent ST with creation of a Bjork flap between 2008 and
      2015. Different outcome parameters, including complications, decannulation,
      inpatient mortality, and surgical characteristics, such as length of surgery and
      height of tracheal incision, were assessed comparing low and high ST. RESULTS:
      Complications occurred in 7.7% of patients, of which persistent stoma (4.1%) and
      hemorrhages (2.7%) were the most common. Low tracheostomy with retraction and
      preservation of thyroid isthmus was done in 31.4% of cases. Complications did not
      significantly differ between low and high tracheostomies (8.0% vs. 7.0%, P =
      .468). Moreover, decannulation rate and inpatient mortality were also not
      significantly different in low compared to high tracheostomies (P = .816 and P =
      .152, respectively). However, low tracheostomies were associated with
      significantly shorter operation times (33.0 +/- 0.8 min vs. 38.7 +/- 0.5 min, P <
      .001) and lower tracheal incisions for creation of a Bjork flap (P < .001)
      compared to high tracheostomies. CONCLUSIONS: Low tracheostomies are as safe as
      high tracheostomies regarding complications. Due to the fact that low
      tracheostomies are associated with shorter operation times and lower tracheal
      incisions, we recommend performong low tracheostomies whenever feasible. LEVEL OF
      EVIDENCE: 4 Laryngoscope, 2018.

PMID- 30284246
TI  - Functional Electrical Stimulation Leads to Increased Volume of the Aged
      Thyroarytenoid Muscle.
AB  - OBJECTIVES/HYPOTHESIS: To reverse sarcopenia and increase the volumes of
      atrophied laryngeal muscles by functional electrical stimulation (FES) using a
      minimal invasive surgical procedure in an aged ovine model. STUDY DESIGN:
      Prospective animal study. METHODS: A stimulation electrode was placed
      unilaterally near the terminal adduction branch of the recurrent laryngeal nerve
      (RLN) adjacent to the right cricothyroid joint. The electrode was connected to an
      implant located subcutaneously at the neck region. Predesigned training patterns
      were automatically delivered by a bidirectional radio frequency link using a
      programming device and were repeated automatically by the implant every other day
      over 11 weeks in the awake animal. Outcome parameters comprised volumetric
      measurements based on three-dimensional reconstructions of the entire
      thyroarytenoid muscle (TAM), as well as gene expression analyses. RESULTS: We
      found significant increases of the volumes of the stimulated TAM of 11% and the
      TAM diameter at the midmembranous parts of the vocal folds of nearly 40%. Based
      on gene expression, we did not detect a shift of muscle fiber composition.
      CONCLUSIONS: FES of the terminal branches of the RLN is a secure and effective
      way to reverse the effects of age-related TAM atrophy and to increase volumes of
      atrophied muscles. LEVEL OF EVIDENCE: NA Laryngoscope, 2018.

PMID- 30284247
TI  - Osseous Changes Over Time in Free Fibular Flap Reconstruction.
AB  - OBJECTIVES/HYPOTHESIS: Evaluate bone resorption in free fibular grafts and
      document resorption behavior as compared to dentulous and edentulous
      autochthonous mandibular bone. STUDY DESIGN: Retrospective Chart review. METHODS:
      Postoperative computed tomography images were used to evaluate fibular graft
      resorption rates and corresponding sites of the dentulous or edentulous mandible.
      Bone height, width, and cortical thickness were measured. RESULTS: Eighteen
      patients underwent fibula free flap reconstruction following resection of a
      primary head and neck cancer. Mandibular defects were classified using Jewer's
      classification. The average interval loss of osseous height was 0.23 +/- 0.09
      mm/yr for fibula flap, 0.55 +/- 0.13 mm/yr for dentulous native mandible, and
      0.98 +/- 0.41 mm/yr in edentulous native mandible. Change in osseous width was
      0.19 +/- 0.08 mm/yr, 0.55 +/- 0.33 mm/yr, and 0.73 +/- 0.15 mm/yr, respectively.
      Rate of superior cortical resorption was 0.33 +/- 0.34 mm/yr, 0.35 +/- 0.13
      mm/yr, and 0.53 +/- 0.11 mm/yr in fibula flap, dentulous, and edentulous
      mandible, respectively. Inferior cortical resorption rates were quantified as
      0.30 +/- 0.11 mm/yr, 0.35 +/- 0.08 mm/yr, and 0.51 +/- 0.08 mm/yr. CONCLUSIONS:
      Fibula free flap reconstruction of the mandible provides excellent functional
      results and allows for stable outcomes. Bone resorption is significantly lower in
      fibular graft compared with both edentulous and dentulous mandible. Edentulous
      bone displays significantly increased rates of atrophy in comparison to the
      dentulous mandible. This may have implications with regard to long-term viability
      of both the fibular flap and native mandible. The role of dental restoration on
      overall osseous stability warrants further research. LEVEL OF EVIDENCE: 4
      Laryngoscope, 2018.

PMID- 30284248
TI  - Sentinel Lymph Node Biopsy Versus Elective Neck Dissection for Stage I to II Oral
      Cavity Cancer.
AB  - OBJECTIVES: Sentinel lymph node biopsy (SLNB) has been shown to be an accurate
      technique for staging the neck in early-stage oral cavity squamous cell carcinoma
      (OCSCC) and has been incorporated in treatment guidelines as an option instead of
      elective neck dissection (END). However, utilization of SLNB in the United States
      remains unclear, and existing prospective studies did not directly compare
      survival between SLNB and END. METHODS: We conducted a retrospective cohort study
      of patients with stage I to II OCSCC (cT1-2cN0cM0) who underwent staging of the
      neck in the National Cancer Data Base from 2012 to 2015. We compared the practice
      patterns and outcomes of patients who underwent SLNB versus END. RESULTS: We
      identified 8,328 eligible patients with a median follow-up of 35.4 months. SLNB
      was used for 240 patients, or 2.9% of stage I to II OCSCC. Completion neck
      dissection was avoided in 63.8% of patients undergoing SLNB. SLNB was associated
      with reduced perioperative morbidity, with median length of hospital stay of 1.0
      days versus 3.0 days after END (P < 0.001). Perioperative 30-day mortality was 0%
      after SLNB versus 0.7% after END (P = 0.42). Overall 3-year survival was 82.0%
      after SLNB and 77.5% after END (P = 0.40). After adjustment, overall survival was
      equivalent between patients who underwent SLNB versus END (adjusted hazard ratio
      1.03, confidence interval 0.67-1.59). CONCLUSIONS: SLNB for stage I to II OCSCC
      is associated with reduced length of hospital stay and equivalent overall
      survival compared with END. Despite these attributes, SLNB remains rarely used in
      the United States. LEVEL OF EVIDENCE: NA. Laryngoscope, 2018.

PMID- 30284249
TI  - Elevation of extracellular osmolarity improves signs of myotonia congenita in
      vitro: a preclinical animal study.
AB  - KEY POINTS: During myotonia congenita, reduced chloride (Cl- ) conductance
      results in impaired muscle relaxation and increased muscle stiffness after
      forceful voluntary contraction. Repetitive contraction of myotonic muscle
      decreases or even abolishes myotonic muscle stiffness, a phenomenon called 'warm
      up'. Pharmacological inhibition of low Cl- channels by anthracene-9-carboxylic
      acid in muscle from mice and ADR ('arrested development of righting response')
      muscle from mice showed a relaxation deficit under physiological conditions
      compared to wild-type muscle. At increased osmolarity up to 400 mosmol L-1 , the
      relaxation deficit of myotonic muscle almost reached that of control muscle.
      These effects were mediated by the cation and anion cotransporter, NKCC1, and
      anti-myotonic effects of hypertonicity were at least partly antagonized by the
      application of bumetanide. ABSTRACT: Low chloride-conductance myotonia is caused
      by mutations in the skeletal muscle chloride (Cl- ) channel gene type 1 (CLCN1).
      Reduced Cl- conductance of the mutated channels results in impaired muscle
      relaxation and increased muscle stiffness after forceful voluntary contraction.
      Exercise decreases muscle stiffness, a phenomena called 'warm up'. To gain
      further insight into the patho-mechanism of impaired muscle stiffness and the
      warm-up phenomenon, we characterized the effects of increased osmolarity on
      myotonic function. Functional force and membrane potential measurements were
      performed on muscle specimens of ADR ('arrested development of righting
      response') mice (an animal model for low gCl- conductance myotonia) and
      pharmacologically-induced myotonia. Specimens were exposed to solutions of
      increasing osmolarity at the same time as force and membrane potentials were
      monitored. In the second set of experiments, ADR muscle and pharmacologically
      induced myotonic muscle were exposed to an antagonist of NKCC1. Upon osmotic
      stress, ADR muscle was depolarized to a lesser extent than control wild-type
      muscle. High osmolarity diminished myotonia and facilitated the warm-up
      phenomenon as depicted by a faster muscle relaxation time (T90/10 ). Osmotic
      stress primarily resulted in the activation of the NKCC1. The inhibition of NKCC1
      with bumetanide prevented the depolarization and reversed the anti-myotonic
      effect of high osmolarity. Increased osmolarity decreased signs of myotonia and
      facilitated the warm-up phenomenon in different in vitro models of myotonia.
      Activation of NKCC1 activity promotes warm-up and reduces the number of
      contractions required to achieve normal relaxation kinetics.

PMID- 30284250
TI  - Tinnitus and taste disturbances reported after myringoplasty: Data from a
      national quality registry.
AB  - OBJECTIVES/HYPOTHESIS: Postoperative tinnitus and taste disturbances after
      myringoplasty are more common than previously reported. STUDY DESIGN: This study
      was a retrospective analysis of prospectively collected data from the Swedish
      National Quality Registry for Myringoplasty. METHODS: The analysis was performed
      on extracted data from all counties in Sweden collected from database A from 2002
      to 2012 and database B from 2013 to 2016. Tinnitus and taste disturbance
      complications 1 year after myringoplasty were analyzed in relation to gender,
      age, procedure, and success rate. In database A, physicians reported tinnitus and
      taste disturbances. In database B, patients reported the complications. RESULTS:
      A major difference was found when the complications were reported by physicians
      compared to when the complications were reported by patients. In database A,
      tinnitus was reported in 1.2% of the patients and taste disturbances in 0.5%. In
      database B, the frequencies were 12.3% and 11.2%, respectively. Tinnitus and
      taste disturbances were more frequent after conventional myringoplasty compared
      to those after fat grafting and were more frequent after primary compared to
      those after revision surgery when reported by physicians. Patients, however,
      reported the same frequency of tinnitus after fat graft myringoplasty compared to
      that after conventional myringoplasty (12.0% vs. 12.6%) and fewer taste
      disturbances after revision surgery. In follow-up assessments, complications
      persisted after surgery over a long time period. CONCLUSION: Tinnitus and taste
      disturbances are more common after myringoplasty when patients report their
      symptoms than when physicians report the symptoms. LEVEL OF EVIDENCE: 2b.
      Laryngoscope, 2018.

PMID- 30284251
TI  - Incidence and Treatment Outcomes of Vocal Fold Movement Impairment After Total
      Arch Replacement.
AB  - BACKGROUND: Vocal fold movement impairment (VFMI) secondary to neuronal injury is
      a known risk after aortic surgery. Total arch replacement is technically
      challenging, and the incidence of vocal fold movement impairment secondary to
      neuronal injury after this surgery is unknown. This study examined the incidence
      of VFMI after total arch replacement and medialization treatment outcomes. STUDY
      DESIGN: Retrospective cohort study. METHODS: All patients who underwent total
      arch replacement at a tertiary care center over 11 years (2006-2017) were
      identified through an institutional database. End points included evidence of
      VFMI on flexible laryngoscopy, time to diagnosis, time to treatment, need for
      reintubation, and intensive care unit (ICU) and hospital length of stay. RESULTS:
      Of the 358 patients who underwent total arch replacement, 63 (20%) were diagnosed
      with VFMI during their initial inpatient stay. Fifty patients (79%) VFMIs were
      left-sided, nine (14%) were right-sided, and four (6%) were bilateral. Thirty
      nine patients (62%) underwent inpatient vocal fold medialization: 28 (72%) by
      injection laryngoplasty and 11 (28%) by type 1 thyroplasty. Those with unilateral
      VFMI had longer ICU (8.9 days) and hospital (19.4 days) than those with no VFMI
      (5.7 and 16.1 days). Among patients with unilateral VFMI, those who underwent
      inpatient vocal fold medialization trended toward shorter ICU (6.2 vs. 14.4 days,
      P = .03) and hospital stays (20.1 vs. 23.3 days, P = .4) than patients who did
      not have a medialization procedure. CONCLUSION: The overall incidence of VFMI
      after total arch replacement in our series was 20%. Both the right and left vocal
      folds are potentially at risk from a total arch replacement; consequently, the
      distribution of injury in our cohort was more heterogeneous than in other series.
      LEVEL OF EVIDENCE: 3. Laryngoscope, 00:1-5, 2018.

PMID- 30284252
TI  - The effect of resveratrol on the histologic characteristics of the cochlea in
      diabetic rats.
AB  - OBJECTIVES/HYPOTHESIS: The aim of this study was to investigate changes in the
      cochlea and the potential dose-dependent effects of resveratrol (RSV) against
      diabetes mellitus (DM) ototoxicity. STUDY DESIGN: Animal model. METHODS: Twenty
      four male Wistar albino rats were divided into four groups. Baseline distortion
      product otoacoustic emission (DPOAE) measurements were evaluated. Group I was the
      control group, group II was made diabetic with single-dose streptozotocin, and
      groups III and IV were rendered diabetic as group II and administered 10 and 20
      mg RSV, respectively, intraperitoneally for 4 weeks. All animals were sacrificed
      after repeated DPOAE measurement. Apoptosis was investigated using caspase-3, Bax
      (Bcl-associated X protein), and TUNEL (terminal deoxynucleotidyl transferase dUTP
      nick end labeling) staining. RESULTS: The DPOAE values in the diabetic group were
      found to be significantly lower compared with the other groups at 5,714 Hz and
      8,000 Hz (P < .05). No significant difference in otoacoustic emission was
      detected in the comparison of the RSV doses (P > .05). The histopathologic
      investigation using caspase-3, Bax, and TUNEL staining showed that the mean rank
      of the diabetic group was significantly higher compared with the RSV10, RSV20,
      and control groups (DM > RSV10 > RSV20 > control) (P < .05). CONCLUSIONS: These
      results imply that RSV administration offered statistically significant
      protection for the cochleas of rats against diabetes. This protective effect
      improved histologically with higher doses. LEVEL OF EVIDENCE: NA Laryngoscope,
      2018.

PMID- 30284253
TI  - Safety and feasibility of a novel recurrent laryngeal nerve monitoring technique.
AB  - OBJECTIVES/HYPOTHESIS: Continuous intraoperative nerve monitoring (CIONM) during
      thyroidectomy is promising technology that may reduce the incidence of recurrent
      laryngeal nerve (RLN) injuries. However, the current technique for CIONM, in
      which a stimulating probe is placed on the vagus nerve, has not been widely
      adopted because of concerns regarding its invasiveness and safety. A new method
      with the lead positioned on the RLN may overcome these objections and promote
      greater adoption of CIONM. This study was conducted to serve as the first step in
      determining the safety and feasibility of an RLN-based CIONM approach. STUDY
      DESIGN: Case series with planned data collection. METHODS: Fifty patients
      scheduled to undergo thyroidectomy were enrolled. In all cases, after
      identification of the RLN, a lead designed for CIONM was placed on the nerve. The
      lead was then left in place for a minimum of 2 minutes, and CIONM data were
      recorded. Laryngeal electromyographic (EMG) characteristics were assessed just
      before the lead was placed on the RLN and after it was removed. Pre- and
      postoperative fiberoptic laryngoscopy was performed to assess vocal cord function
      in all patients. RESULTS: In 49 patients (98%), the probe was successfully
      positioned on the RLN, and CIONM data were generated. On average, 1.4 attempts
      per patient were required to properly place the lead. No accidental dislodgements
      of the lead occurred during the experiments. No patients demonstrated significant
      EMG changes from baseline after manipulation and stimulation of the RLN. The
      average CIONM time was 175.7 s (range, 138-212 s), and the average CIONM
      amplitude and latency were 675.2 uV (range, 211.0-1405.2 uV) and 1.8 ms (1.25
      1.9), respectively. All patients had normal bilateral vocal cord function
      preoperatively and at the first postoperative visit. CONCLUSIONS: This study
      demonstrates the apparent safety and viability of a CIONM technique using a lead
      placed directly on the RLN. Future investigations are warranted of this promising
      method, which may promote more widespread adoption of CIONM during thyroidectomy
      to reduce RLN injuries. LEVEL OF EVIDENCE: 4 Laryngoscope, 2018.

PMID- 30284254
TI  - Impact of Age on Sinus Surgery Outcomes.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the impact of age on patient-reported quality
      of life (QOL) following endoscopic sinus surgery (ESS) for chronic rhinosinusitis
      (CRS). STUDY DESIGN: Prospective cohort study. METHODS: Six hundred thirty-six
      patients with CRS were recruited from 11 otolaryngologic practices and completed
      the sinonasal-specific, 22-item Sino-Nasal Outcome Test-22 (SNOT-22) and general
      health-related EuroQol 5-Dimension (EQ-5D) questionnaires at baseline and 12 and
      24 months after ESS. Patients were grouped chronologically to determine whether
      age at time of ESS was associated with clinical outcomes. RESULTS: Ages ranged
      from 18 to 80 years (mean +/- standard deviation = 48.5 +/- 14.4). Improvement
      was observed in postoperative SNOT-22 scores at 12 and 24 months for all decades
      of life. Similar improvements were observed for EQ-5D-based health utility value
      (HUV) scores in all decades of life, except for the eldest cohort (ages 70-80, N
      = 33), who did not exceed the minimal clinically important difference at either
      12 or 24 months following ESS. In regression analysis, age was not associated
      with sinonasal-specific outcomes (change in SNOT-22 scores) at 12 (P = .507) or
      24 months (P = .955). In general health-related outcomes, however, age was
      significantly associated with change in EQ-5D-based HUV scores from baseline to
      12 months following ESS after adjusting for patient demographics, comorbidities,
      and surgical history (P = .049). CONCLUSIONS: This study demonstrates that ESS
      for adult CRS sufferers offers improved QOL outcomes through the eighth decade of
      life. The impact of comorbidities on QOL needs to be carefully considered when
      assessing older patients for sinus surgery. LEVEL OF EVIDENCE: 2b Laryngoscope,
      2018.

PMID- 30284255
TI  - Risk factors for thyroid surgery-related unilateral vocal fold paralysis.
AB  - OBJECTIVES/HYPOTHESIS: We aimed to identify the risk factors for iatrogenic
      unilateral vocal fold paralysis (UVFP) caused by thyroid surgery, to allow the
      identification of patients requiring nerve-protection procedures and monitoring
      technologies. STUDY DESIGN: Retrospective case study in a medical center.
      METHODS: Patients who underwent thyroid surgery from April 2011 to February 2016
      and who were diagnosed with UVFP by laryngoscopy and laryngeal electromyography
      were included. Patient demographics, types of surgery, and characteristics of the
      thyroid lesions were analyzed. RESULTS: Sixty (2.1%) of 2,815 patients who
      received thyroid surgery developed UVFP. The risk of UVFP was higher in patients
      over 60 years old (odds ratio, 1.89; 95% confidence interval, 1.01-3.26; P =
      .01). Involvement of the external branch of superior laryngeal nerve (EBSLN)
      occurred in 19 (31.7%) of the 60 UVFP patients, and was more likely to occurr in
      patients with diabetes mellitus (odds ratio, 14.19; 95% confidence interval, 3.80
      52.94; P < .001). The incidence of UVFP and involvement of the EBSLN differed
      among surgery types, and was the highest among patients undergoing total
      thyroidectomy with neck dissection (TTND) (10/158, 6.3% and 5/158, 3.2%,
      respectively). CONCLUSIONS: The risk of thyroid surgery-related UVFP is higher in
      older patients. EBSLN involvement is more likely in patients with diabetes
      mellitus. TTND is associated with higher risks of UVFP and EBSLN injury than
      other types of surgery, implying the need of intraoperative nerve monitoring in
      these high-risk characteristics. LEVEL OF EVIDENCE: 4 Laryngoscope, 2018.

PMID- 30284256
TI  - Percutaneous versus surgical tracheostomy: timing, outcomes, and charges.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study was to compare timing of
      procedure, patient characteristics, outcomes, and charges for patients who
      underwent percutaneous versus surgical tracheostomy. STUDY DESIGN: Retrospective
      cohort study. METHODS: A retrospective analysis was performed for all patients
      who underwent tracheostomy in 2015 to 2016 in New York State. Patients were
      identified using International Classification of Diseases, 10th Revision,
      Clinical Modification codes and stratified to the type of tracheostomy performed.
      The primary outcome of interest was mortality at index stay. Secondary outcomes
      of interest included length of stay and total hospitalization charges. RESULTS:
      Of the 8,682 patients, 2,488 (28.7%) underwent percutaneous and 6,194 (71.3%)
      underwent surgical tracheostomy. At hospitals where both procedures were
      performed, percutaneous tracheostomy patients were older, had more comorbidities,
      and had lower income (P < .05). Timing of the tracheostomy relative to admission
      did not affect the type of tracheostomy performed. While controlling for patient
      characteristics and complications during the visit, percutaneous tracheostomy was
      associated with increased mortality (odds ratio [OR]: 1.17, 95% confidence
      interval [CI]: 1.03-1.33, P = .0153) and increased hospital charges (OR: + 7.76%,
      95% CI: 5.4-10.11, P < .0001). Length of stay was not affected by procedure type.
      CONCLUSIONS: Surgical tracheostomies are more commonly performed than
      percutaneous tracheostomies across New York State. Older, lower-income, and
      sicker patients have a higher chance of receiving percutaneous tracheostomies.
      Percutaneous approaches were associated with statistically significant increased
      mortality and higher charges despite no difference in length of stay. Further
      studies are needed to determine if these differences in outcomes are clinically
      significant. LEVEL OF EVIDENCE: NA Laryngoscope, 2018.

PMID- 30284257
TI  - The Impact of Duty-Hour Restrictions on Complication Rates Following Major Head
      and Neck Procedures.
AB  - OBJECTIVES/HYPOTHESIS: To assess the impact of resident duty-hour restrictions
      (DHR) in otolaryngology via comparison of postoperative outcomes between
      otolaryngology teaching hospitals (Oto-TH) and nonteaching hospitals (NTH) before
      and after complete implementation. STUDY DESIGN: Retrospective database review.
      METHODS: The Nationwide Inpatient Sample was queried for all major head and neck
      cases between 2000 and 2002 (n = 34,064) and 2008 and 2010 (n = 33,094). Cases
      were stratified into Oto-TH (n = 28,771) and NTH (n = 38,387) and assessed for
      procedure type, patient comorbidities, and complications. A subpopulation matched
      by procedure type was generated for direct comparison of complication rates using
      chi2 and binary logistic regression analyses. RESULTS: In the years following
      DHR, total case volume and average case complexity increased at Oto-TH only.
      Using a case-matched subpopulation, regression analysis found Oto-TH status to be
      protective for medical complications both before (odds ratio [OR]: 0.60, P <
      .001) and after (OR: 0.76, P = .001) DHR. In contrast, Oto-TH cases had lower
      risk for surgical complications in 2000 to 2002 (OR: 0.77, P < .001) but not 2008
      to 2010 (OR: 1.07, P = .275). When comparing time periods, the years following
      DHR were associated with a significant decrease in medical complications and
      mortality across hospital cohorts. For surgical complications, rates
      significantly improved at NTH only (OR: 0.82, P = .002), with no difference at
      Oto-TH (OR: 0.95, P = .450). CONCLUSIONS: In the years following DHR, rates of
      medical complications, surgical complications, and mortality have significantly
      improved at NTH. At Oto-TH, there has been a lack of similar improvement in
      surgical complications, even after accounting for increasing case volume and
      complexity in more recent years. While the cause is likely multifactorial, DHR in
      otolaryngology residency may play a role. LEVEL OF EVIDENCE: 4 Laryngoscope,
      2018.

PMID- 30284258
TI  - Meta-Analysis of Obstruction Site Observed With Drug-Induced Sleep Endoscopy in
      Patients With Obstructive Sleep Apnea.
AB  - OBJECTIVE: To perform a meta-analysis on the distribution and characteristics of
      the obstructive site in patients with obstructive sleep apnea (OSA) using data
      from a variety of published studies that evaluated the obstruction with drug
      induced sleep endoscopy (DISE). METHODS: A literature search was performed to
      identify studies in which DISE was used to identify the obstruction site in adult
      patients with OSA, and the obstruction site was described in sufficient detail.
      Four items were evaluated in the meta-analysis: the obstruction site, closing
      direction of the soft palate, degree of closure, and percentage of single-level
      obstructions. RESULTS: A total of 2,950 patients from 19 studies were included.
      In the two-level classification system, the rate of obstruction was 91.6% for the
      soft palate and 58.0% for the tongue base. In the four-level classification
      system, the rate of obstruction was 84.1% for soft palate, 32.8% for the tonsil,
      51.6% for the tongue base, and 34.3% for the epiglottis. The soft palate closed
      in the anteroposterior direction at a rate of 44.4% and in the concentric
      direction at a rate of 46.5%. The rate of a closure of 75% or more was 69.3% for
      the soft palate and 56.8% for the hypopharynx. The percentage of single-level
      obstructions was 42.5%. CONCLUSION: The soft palate is obstructed in most
      patients with OSA, and the tongue base is obstructed in half of the patients. In
      addition, multilevel obstructions including the tonsil, lateral pharyngeal wall,
      or epiglottis are common; thus, these areas must be checked carefully. LEVEL OF
      EVIDENCE: NA. Laryngoscope, 2018.

PMID- 30284259
TI  - Transfusion of group a low-titer anti-B liquid plasma to a trauma patient in a
      helicopter.

PMID- 30284260
TI  - In response to letter: OSA and BP: Too good to be true?

PMID- 30284261
TI  - Intraoperative Margin Control in Transoral Approach for Oral and Oropharyngeal
      Cancer.
AB  - OBJECTIVES: Piecemeal resection provides an innovative conceptual tool for
      margins surveillance because it entails the intraoperative evaluation of the
      whole resection margins and not just sample points, which should result in a
      better control of deep margins compared to en bloc resection. Although it is
      recognized that the intraoperative use of narrow band imaging (NBI) results in a
      better control of superficial margins, in this exploratory study we investigated
      whether NBI and piecemeal resection could be used in combination to improve
      margin control at both superficial and deep levels. Because piecemeal resection
      is based on frozen section analysis, we wanted to verify its reliability compared
      to definitive histological examination. METHODS: The status of resection margins
      in a group of patients with oral and oropharyngeal cancers treated with NBI and
      laser CO2 piecemeal resection (group 1) was compared with that of an historical
      group of patients (group 2) treated with NBI and conventional en bloc resection.
      In group 1, sensitivity, specificity, and positive and negative predictive values
      were used to verify the rate of concordance between frozen section and definitive
      histology. RESULTS: The difference between deep positive margins in the two
      groups was statistically significant (P = 0.042). The high sensitivity and
      specificity (94.6% and 94.7%, respectively) of frozen section analysis also
      demonstrated its reliability in the examination of larger samples corresponding
      to the whole margin. CONCLUSION: Even if our findings are limited by the small
      number of patients, we are confident that the combined use of NBI and piecemeal
      resection could represent an attractive surgical strategy to improve margin
      control. LEVEL OF EVIDENCE: 2b. Laryngoscope, 2018.

PMID- 30284262
TI  - "Rare" reagent red cells: rare no longer?

PMID- 30284263
TI  - Hemolytic adverse effects of intravenous immunoglobulin: modeling predicts risk
      reduction with anti-A/B immunoaffinity chromatography and to a lesser extent with
      anti-A donor screening.
AB  - BACKGROUND: The risk of hemolytic events (HEs) with intravenous immunoglobulin
      (IVIG) therapy appears to be linked to isoagglutinins (anti-A and anti-B) in the
      product. Patient risk factors include high IVIG dose, blood group, and underlying
      inflammatory state. STUDY DESIGN AND METHODS: Using published anti-A and anti-B
      titers for IVIG products and HE rates calculated from HEs spontaneously reported
      to EudraVigilance, regression models were developed to infer the relationship
      between HE risk and IVIG isoagglutinin levels for each blood group. Applying
      estimated model coefficients to isoagglutinin levels associated with an IVIG
      (Privigen; CSL Behring, King of Prussia, PA), manufactured with and without
      isoagglutinin reduction steps, predicted HE risk values were generated for each
      product: 1) without any isoagglutinin reduction, 2) anti-A donor screening, and
      3) anti-A/anti-B specific immunoaffinity chromatography (IAC; Ig IsoLo). RESULTS:
      Predicted HE risk was highest for blood group AB, followed by A and B; it was low
      for O. Projected population shares of HEs by blood group were similar to reported
      real-world data. Compared with the original process (no isoagglutinin reduction),
      the model predicts lower hemolytic risk with anti-A donor screening and even
      lower hemolytic risk with IAC isoagglutinin reduction. CONCLUSION: IAC
      isoagglutinin reduction is predicted to reduce the HE risk with IVIG
      substantially. Physicians should be especially vigilant to HE risk in patients
      with blood group AB and, to a lesser extent, A when using IVIG products with high
      anti-A titers.

PMID- 30284264
TI  - Transoral Thyroidectomy Using A Flexible Robotic System: A Preclinical Cadaver
      Feasibility Study.
AB  - OBJECTIVES/HYPOTHESIS: Traditionally, most thyroid surgery utilizes a curvilinear
      cervical incision with a resulting permanent scar. Minimally invasive and remote
      access thyroid surgery techniques continue to evolve. Transoral approaches
      through a vestibular incision have been developed at several centers throughout
      the world, obviating the need for a cutaneous incision and optimizing aesthetics.
      To date this technique has been performed using rigid endoscopes or a linear
      robotic platform. The goal of this study was to test the feasibility of a novel
      flexible robotic system to perform a transvestibular thyroidectomy in a
      preclinical cadaver model. STUDY DESIGN: Preclinical feasibility study. METHODS:
      Right and left thyroid lobectomies were successfully performed via a
      transvestibular approach in four cadavers. RESULTS: A single vestibular incision
      between bilateral mental nerves allowed entrance of the flexible robot in a
      subplatysmal plane in both male and female cadavers. The recurrent laryngeal
      nerves and parathyroids were identified and preserved. The flexible three
      dimensional camera allowed excellent visualization and could be easily
      repositioned for optimal visualization of right and left structures. The flexible
      and wristed instruments enabled an atraumatic approach and allowed for precise
      surgical technique. CONCLUSIONS: The transoral vestibular approach to the central
      neck is a promising technique for thyroidectomy with optimal cosmesis and can be
      successfully accomplished using this novel flexible robotic system. Improvements
      in visualization and access offered by this system may improve application of
      this technique. LEVEL OF EVIDENCE: NA Laryngoscope, 2018.

PMID- 30284265
TI  - Medical Versus Surgical Treatment of Pediatric Acute Mastoiditis: A Systematic
      Review.
AB  - OBJECTIVE: There is no standard of care for treatment of pediatric acute
      mastoiditis (PAM). We systematically reviewed the English literature to evaluate
      the efficacy of PAM treatment options. METHODS: PubMed, Embase, MEDLINE,
      Cumulative Index to Nursing and Allied Health Literature, and the Cochrane
      Library were searched from inception to January 2016, along with manual
      bibliography searches, for studies describing surgical or medical therapy. Two
      independent evaluators reviewed each abstract and article. RESULTS: We identified
      310 articles, and 55 met inclusion criteria. Thirty-three evaluated surgical
      options and included 2,930 patients (mean age = 2.8 years) including those with
      myringotomy +/- tube placement (n = 920); 140 needed additional surgery, drainage
      of subperisoteal abscess (SPA) (n = 142) +/- myringotomy or tube placement, 29
      patients needed additional surgery and mastoidectomy +/- myringotomy or tube
      placement (n = 612), with 611 reporting resolution. Using a random effects model,
      the estimated success probability with 95% confidence intervals (CI) are
      myringotomy +/- tube placement 94% (95% CI: 84.5%-97.8%), and drainage of
      subperiosteal abscess with concurrent myringotomy +/- tube placement was 86.5%
      (95% CI: 66.4%-95.4%). Using a random effects model, mastoidectomy success was
      99.7% (95% CI: 77.5%-100%). Nineteen studies evaluated medical therapy (n = 990
      patients). The average cure rate was 71.7% (median = 70%; range, 26.3%-100%), and
      estimated success was 72.9% (95% CI: 60.5%-82.5%) by meta-analysis. CONCLUSIONS:
      Myringotomy with or without tube placement and mastoidectomy have the highest
      cure rates for PAM. With SPA, incision and drainage with myringotomy with or
      without tube can be considered. Medical treatment cured nearly 72% of children.
      Ultimately, management should be based on surgeons' experience and judgment,
      patient characteristics, and severity of disease. Laryngoscope, 2018.

PMID- 30284266
TI  - The use of low-titer group O whole blood for the resuscitation of civilian trauma
      patients in 2018.

PMID- 30284267
TI  - Dexpramipexole depletes blood and tissue eosinophils in nasal polyps with no
      change in polyp size.
AB  - OBJECTIVE: Chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilia is
      a disease of the upper respiratory tract for which few therapies are available.
      Because the oral investigational drug dexpramipexole serendipitously decreased
      blood eosinophils in amyotrophic lateral sclerosis studies, we assessed its
      safety, eosinophil-lowering activity, and preliminary clinical efficacy in
      patients with CRSwNP and eosinophilia. METHODS: Sixteen subjects with CRSwNP,
      absolute eosinophil count (AEC) >= 0.300 * 109 /L, and polyp tissue eosinophils
      were evaluable for efficacy in a 6-month open-label, multi-center study of
      dexpramipexole 150 mg twice daily. The coprimary endpoints were change in AEC and
      change in total polyp score (TPS) from baseline to month 6, with additional
      clinical and histologic endpoints assessed. RESULTS: Thirteen of 16 subjects
      completed 6 months of dexpramipexole treatment. Geometric mean baseline AEC was
      0.525 +/- 0.465 eosinophils * 109 /L and decreased to 0.031 +/- 0.019 after 6
      months of dexpramipexole treatment, a 94% reduction (P < 0.001). Ten of 16
      subjects had eosinophil counts reduced to <= 0.020 * 109 /L at month 6. In 12
      subjects with nasal polyp biopsies at baseline and month 6, tissue eosinophils
      were reduced from a mean of 168 +/- 134 to 5 +/- 2 per high-power field (HPF) (P
      = 0.001), a 97% reduction from baseline. There was no significant reduction in
      TPS or improvement in other clinical endpoints. Dexpramipexole was well
      tolerated, with no drug-related serious adverse events. CONCLUSION:
      Dexpramipexole treatment produced profound eosinophil-lowering in peripheral
      blood and nasal polyp tissue. Despite the near-elimination of polyp eosinophils,
      decreased TPS and nasal symptom improvement were not observed. LEVEL OF EVIDENCE:
      2. Laryngoscope, 2018.

PMID- 30284268
TI  - Is hearing preserved following radiotherapy for vestibular schwannoma?

PMID- 30284269
TI  - Clinical Implications of Intralesional Steroid Injections in the Management of
      Otohematoma.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the long-term effects of intralesional steroid
      injections (ILSIs) in patients with otohematoma and to suggest the clinical
      implications, especially with regard to the duration of otohematoma. STUDY
      DESIGN: Retrospective analysis. METHODS: Fifty-six patients were enrolled and
      classified into short-term otohematoma (n = 30) and long-term otohematoma (n =
      26) groups according to the period of time after auricular trauma. After the
      first ILSI, all patients underwent weekly examinations during the 21-day
      observational period to determine the treatment outcomes and were then followed
      up for reevaluation for a maximum of 36 months. We considered ILSIs to be
      ineffective if the otohematoma persisted after the third ILSI, and we opted to
      perform surgical treatment in such cases. In addition, we evaluated early
      recurrence, late recurrence, and ILSI-related complications. RESULTS: After up to
      three ILSIs, 29 out of 30 cases (96.7%) with short-term otohematoma and 20 out of
      26 cases (76.9%) with long-standing otohematoma were treated without
      complications. Three patients with long-term otohematoma, however, experienced
      late recurrences at 4, 15, and 18 months, respectively. Seven patients who showed
      no response after ILSIs underwent surgical treatment. The duration of otohematoma
      (P = .043) and a higher initial aspirated fluid volume (P = .014) were shown to
      significantly increase the risk of treatment failure after ILSIs. CONCLUSIONS:
      Multiple and immediate ILSIs in patients with otohematoma appear to be an
      effective treatment approach with no complications. Patients with short-term
      otohematoma showed better outcomes following ILSIs. The treatment approach may be
      optimized based on the duration and degree of otohematoma. LEVEL OF EVIDENCE: 4
      Laryngoscope, 2018.

PMID- 30284270
TI  - A pilot study assessing clinic value in pediatric pharyngeal dysphagia: The
      OPPS/cost method.
AB  - OBJECTIVES/HYPOTHESIS: Given the costs of healthcare, capitation, and desires for
      quality improvement (QI), there is a need to better assess healthcare value. Time
      driven activity-based costing and the Quadruple Aim have evaluated value by
      assessing health outcomes and provider experiences relative to costs. The
      proposed OPPS/Cost method expands on this to examine value for aerodigestive
      clinic treatment of pediatric persistent pharyngeal dysphagia: O + P1  + P2  +
      S/Cost (O = objective health [video-fluoroscopic swallow study results], P1  =
      patient/family experience [Consumer Assessment of Healthcare Providers and
      Systems], P2  = provider experience [Copenhagen Burnout Inventory {CBI}], S =
      subjective health [Feeding/Swallowing-Impact Survey], C = cost [time-driven
      activity-based costing]). STUDY DESIGN: Use of QI time data, surveys, and
      retrospective chart review for 56 patient encounters. METHODS: Staff interviews
      were used to develop process maps, and monetary values were assigned to
      activities. OPPS/Cost outcomes were normalized amongst variables, and composite
      values were calculated. Comparisons were made using a Student t test for pre- and
      postclinic relocation over a 14-month period. RESULTS: Time reductions were check
      in (13 minutes/patient), rooming (21 minutes/patient), and providers (4
      minutes/patient). Patient in-room wait time increased (4 minutes/patient). The
      CBI identified burnout as an area for improvement. OPPS/Cost composite values
      increased by 14%, with a 1.7% cost reduction, improvement in objective and
      subjective health outcomes of 47.4% (P < .05) and 7.3%, respectively, and stable
      patient/family experience. CONCLUSIONS: OPPS/Cost is feasible in an
      interdisciplinary clinic and helped evaluate value during a clinic relocation.
      The QI opportunities identified are indicative of the potential of OPPS/Cost.
      LEVEL OF EVIDENCE: NA Laryngoscope, 2018.

PMID- 30284271
TI  - Clinical Trials in Obstructive Sleep Apnea: Recognizing Trends and Future
      Opportunities.
AB  - OBJECTIVES/HYPOTHESIS: Examine US and international clinical trials in
      obstructive sleep apnea (OSA) to characterize researchers involved, interventions
      being studied, and opportunities for future investigation. STUDY DESIGN:
      Retrospective database review. METHODS: The information from ClinicalTrials.gov
      was used to assess OSA clinical trials between 1999 and 2017. Information was
      gathered on principle investigator (PI) demographics, interventions studied,
      study funding source, and regional distribution of research institutions.
      RESULTS: There were 813 clinical trials studied. The majority of trials examined
      continuous positive airway pressure interventions (43.7%), with pharmacotherapies
      being the second most commonly investigated treatment (19.2%). Surgical
      interventions made up 10.7% (n = 87) of clinical trials for OSA. Most studies
      were based internationally (59.9%). PIs were predominantly male (72.0%); 72.7%
      had an MD and 28.6% had a PhD. There were no significant differences in funding
      source (National Institutes of Health vs. industry, P = .14) or institutional
      geography (international vs. US, P = .73) between surgical and nonsurgical
      studies. Surgical trials were significantly more likely to have a male PI and
      involve pediatric patients compared to nonsurgical trials (P < .001).
      Otolaryngologists represented 9.2% of all PIs and had similar rates of NIH
      funding compared to other medical specialists (P = .22). CONCLUSIONS: This study
      provides a broad overview of past, current, and future treatment paradigms for
      OSA. Sleep surgery, specifically otolaryngology, is a small voice in the overall
      landscape of clinical trials for OSA. This information can help guide future
      research efforts and direct our specialty when setting priorities regarding
      research funding while encouraging a broad and interdisciplinary pursuit. LEVEL
      OF EVIDENCE: NA. Laryngoscope, 2018.

PMID- 30284272
TI  - Appropriateness Criteria for Surgery in the Management of Adult Recurrent Acute
      Rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: Endoscopic sinus surgery (ESS) is frequently performed for
      recurrent acute rhinosinusitis (RARS). Appropriate indications for surgery among
      patients with RARS have not yet been rigorously determined. The objective of this
      study was to define appropriateness criteria for ESS in the management of adult
      RARS. STUDY DESIGN: Application of RAND-UCLA appropriateness methodology.
      METHODS: A panel of nine multidisciplinary experts in RARS was formed to evaluate
      RARS scenarios generated from current evidence. The panel completed two rounds of
      a modified Delphi-ranking process and a teleconference. RESULTS: A total of 32
      clinical scenarios were ranked in each round. For adult patients with RARS, ESS
      can appropriately be offered as a treatment option when patients experience >=
      four annual episodes, and there is confirmation of at least one episode via
      computed tomography or nasal endoscopy, and the patient and clinician jointly
      participate in shared decision making, and the patient has either failed a trial
      of topical nasal steroids or experienced RARS-related productivity loss.
      CONCLUSIONS: This study has defined appropriateness criteria for ESS as a
      management option for adult patients with RARS. These criteria are intended to
      represent a minimum threshold for which ESS should be considered in the treatment
      of RARS and do not suggest that all patients who meet these criteria should
      undergo surgery. These criteria may serve as a baseline set of indications for
      ESS in patients with RARS. LEVEL OF EVIDENCE: NA. Laryngoscope, 2018.

PMID- 30284273
TI  - Long-Term Outcome of Hearing Rehabilitation With An Active Middle Ear Implant.
AB  - OBJECTIVE: To assess the audiological and long-term medical and technical follow
      up outcomes of an active middle ear implant. METHODS: This was a retrospective
      medical chart analysis of all patients provided with an active middle ear implant
      in a tertiary academic medical referral center between September 1, 1998, and
      July 31, 2015. Main outcome measures were medical and technical complications,
      revisions, reimplantations, explantations, coupling approaches, mean time of use,
      pre- and postoperative hearing thresholds, functional hearing gain across
      frequencies (250-4,000 Hz), and Freiburg monosyllablic word test at 65 dB.
      RESULTS: One hundred and three patients were identified. Fifteen were implanted
      bilaterally (n = 118 Vibrant Soundbridge devices [MED-EL, Innsbruck, Austria]).
      Seventy-seven devices were implanted for sensorineural and 41 for mixed and
      conductive hearing loss. Patients used the implant for 6.7 years (range 0.7
      months-17.9 years) on average. Ninety-one patients (77.12%) were using the device
      at the end of the observation period. An overall complication rate of 16.1% was
      observed. The revision and explantation rates were higher for devices implanted
      between 2004 and 2006. The device failure rate was 3.4%. Audiological evaluation
      showed significant hearing gains for both hearing loss patient groups.
      CONCLUSION: This long-term follow-up reveals the reliability of the active middle
      ear implant in a single center. Overall complication rate and device failure rate
      are acceptable. The complication rate was higher during implementation of
      alternative coupling approaches. The audiological benefit was satisfactory in
      patients with all hearing loss types. The majority of implanted patients used the
      implant at the end of the observation period. LEVEL OF EVIDENCE: 4. Laryngoscope,
      2018.

PMID- 30284275
TI  - How I reduce the risk of missed irradiation transfusion events in children.

PMID- 30284274
TI  - Computerized Tomography Analysis of Young Children for Prevention of Aspiration
      Injuries.
AB  - OBJECTIVE: The Small Parts Test Fixture (SPTF) (16 CFR 1501) was developed from
      cadavers of young children and foreign body (FB) data. Recent FB studies reveal
      that the SPTF misses outliers. Computerized tomography (CT) provides detailed
      dimensional data for young children. Our null hypothesis is that the SPTF (31.75
      mm) is smaller than relevant portions of the aerodigestive tract. METHODS: A 3
      year retrospective review (2011-2014) of head/neck CT data for infants and
      children (N = 106) aged 6 months to 6 years was completed. Six measurements (mm)
      were recorded: 1) maxillary incisors to posterior edge of hard palate (MI/HP); 2)
      posterior edge of hard palate to first cervical (C1) vertebra (HP/C1); 3) soft
      palate to posterior pharyngeal wall; and 4) interpalatine tonsillar distance; 5,
      6) larynx diameter, and width. Two ratios were calculated: 1) ratio of lengths
      (hard palate to soft palate), and 2) laryngeal dimensional ratio. RESULTS: A
      linear trend of increasing dimensions with increased age was noted. The length
      measured MI/HP best correlates with known data of potential FBs causing injury or
      death. This MI/HP length can range from 33.8 to 45.8 mm for all children younger
      than 3 years of age and exceeds the SPTF diameter (31.75 mm). There were no
      statistical anatomical differences by gender in any of the age groups.
      CONCLUSION: Computed tomography measurements appear larger than SPTF values
      developed from cadavers. These CT data support enlargement of the SPTF to enhance
      safety for choking hazards in children. LEVEL OF EVIDENCE: 4. Laryngoscope, 2018.

PMID- 30284277
TI  - Clinical Characteristics of Bilateral Meniere's Disease in a Single Asian Ethnic
      Group.
AB  - OBJECTIVES/HYPOTHESIS: To identify the clinical characteristics of patients with
      bilateral Meniere's disease (MD) in an Asian population. STUDY DESIGN: Cross
      sectional retrospective study. METHODS: We compared the clinical features of
      bilateral MD (BMD) and unilateral MD (UMD) in 320 Asian patients with single
      ethnicity. Demographic variables; age of onset; inner ear function; the
      coexistence of related disorders such as vestibular migraine, delayed MD,
      systemic autoimmune diseases, and familial MD; and prognoses were analyzed and
      compared. RESULTS: The overall prevalence of BMD was 5.6%. The mean age of
      disease onset was 40.3 +/- 14.8 and 47.0 +/- 14.1 years for patients with BMD and
      UMD, respectively (P = .07). Demographic variables were not significantly
      different between patients with BMD and UMD (P > .05). Inner ear function,
      evaluated by hearing thresholds, caloric tests, and cervical vestibular evoked
      myogenic potentials, was significantly more deteriorated in the first involved
      ear of patients with BMD than in the second involved ear or the affected side of
      patients with UMD (P < .05). Among the comorbid conditions, only the prevalence
      of delayed MD was significantly higher in patients with BMD than in patients with
      UMD. Systemic autoimmune disease was found in only three patients with UMD. There
      was no significant prognostic difference between patients with UMD and BMD (P >
      .05). CONCLUSIONS: A low prevalence of BMD, a higher frequency of delayed MD in
      BMD patients, and a low frequency of systemic autoimmune diseases in both UMD and
      BMD patients are significant findings in an Asian population. LEVEL OF EVIDENCE:
      4 Laryngoscope, 2018.

PMID- 30284276
TI  - Intratympanic Therapies in Meniere Disease: Evaluation of Outcomes and Early
      Vertigo Control.
AB  - OBJECTIVE: To evaluate outcomes of intratympanic (IT) dexamethasone and
      gentamicin in Meniere Disease (MD). METHODS: Charts of adult patients with
      unilateral definite MD receiving IT gentamicin or dexamethasone from 2005 to 2017
      were retrospectively reviewed. All patients had at least 6 months follow-up.
      Failure in each group was defined as the need for more aggressive therapy. Prior
      to 2011, all patient received IT gentamicin, administered as primary therapy
      after failure of conservative treatment measures. Gentamicin was administered
      every 2 weeks, up to three injections, until vertigo control was achieved.
      Beginning in 2011, the treatment protocol shifted to IT dexamethasone as initial
      treatment, with gentamicin used for dexamethasone failures. Dexamethasone was
      administered weekly for up to three injections. Treatments could be repeated if
      symptoms recurred. RESULTS: Thirty-three patients received IT dexamethasone, and
      70 patients received IT gentamicin. Dexamethasone patients received a mean of 3.3
      injections compared to 2.7 in the gentamicin group (P = 0.011). There were 12
      (38%) failures in the dexamethasone group and only seven (10%) gentamicin
      failures (P = 0.025). No patients failed both treatments. The mean time to
      failure in the dexamethasone group was 5 months, whereas in the gentamicin group
      it was 27 months. Change in pure tone audiometry from baseline was not different
      between treatment groups (P = 0.30). CONCLUSION: Subjects receiving IT gentamicin
      required fewer injections and had a significantly longer time to failure than IT
      dexamethasone. Audiometric outcomes were similar between the groups. The use of
      IT gentamicin as initial therapy for early and long-term control of MD is safe
      and effective. LEVEL OF EVIDENCE: 3. Laryngoscope, 2018.

PMID- 30284278
TI  - Comparison of Modern Rigid Fixation Plating Outcomes for Segmental Mandibular
      Microvascular Reconstruction.
AB  - OBJECTIVES/HYPOTHESIS: New advances in osseous microvascular mandibular rigid
      fixation are being employed at many institutions. These include standardized
      prebent/preformed reconstruction plates as well as computer-aided design/computer
      aided manufacturing (CAD/CAM) custom plates that are patient specific. Our goal
      was to assess and compare the outcomes of both of these new technologies when
      utilized for mandibular microvascular reconstruction. STUDY DESIGN: Retrospective
      chart review. METHODS: Subjects were categorized into two groups according to
      their mandibular rigid fixation technique: group 1 = prebent/preformed plates and
      group 2 = CAD/CAM custom plates. Primary outcome measures were 1) perioperative
      complications (defined as deep tissue infection, wound dehiscence resulting in
      bone exposure, and/or plate exposure) and 2) reoperation rates for mandibular
      hardware failure/explantation. Statistical analysis consisted of chi2 , Fisher
      exact test, and multivariable regression models. RESULTS: A total of 142 subjects
      underwent microvascular mandibular reconstruction in a 6-year period. Eighty-nine
      subjects utilized prebent/preformed plates, and 53 employed CAD/CAM custom
      plates. Perioperative complications occurred in 32 of 89 (35.9%) subjects with
      prebent/preformed plates and 11 of 53 (20.7%) subjects using CAD/CAM custom
      plates. Reoperation requiring hardware explantation occurred in 18 of 89 (20.2%)
      subjects and three of 53 (5.6%) using CAD/CAM custom plates. Statistical
      comparison of perioperative complications between the two groups approached
      significance (P = .0556), and the rate of reoperation was significant favoring
      CAD/CAM implants (P = .0180). CONCLUSIONS: In our experience, CAD/CAM custom
      plates utilized for rigid fixation during microvascular mandibular reconstruction
      demonstrated fewer complications and statistically lower reoperation rates when
      compared with prebent/preformed plates. LEVEL OF EVIDENCE: 2c Laryngoscope, 2018.

PMID- 30284279
TI  - Loss of Microbial Niche Specificity Between the Upper and Lower Airways in
      Patients With Cystic Fibrosis.
AB  - OBJECTIVES/HYPOTHESIS: To determine the relationship between mucosal-associated
      sinus and bronchial microbiota in cystic fibrosis (CF) patients compared to non
      CF patients with chronic rhinosinusitis (CRS). STUDY DESIGN: Case series.
      METHODS: We examined the microbial composition of 52 paired sinus and bronchial
      brushings from 26 patients with CRS. Paired airway samples from nine subjects
      with CF were compared with samples from 17 non-CF-CRS disease control patients.
      The Illumina MiSeq platform was used to sequence the V4 region of the 16S rRNA
      gene. Sequences were analyzed using QIIME 1.9.0. RESULTS: CF patients demonstrate
      increased severity of sinus inflammation (Lund-Mackay score 16.3 vs. 12.4, P =
      .023) and diminished diversity of microbial communities in both the sinuses
      (Shannon diversity 0.98 vs. 3.3, P = .009) and lungs (Shannon diversity 2.2 vs.
      4.0, P = .042) relative to non-CF-CRS. Non-CF-CRS sinus and lung microbiota were
      distinct and clustered by niche (sinus vs. lung, P = .004). However, CF airway
      microbiota demonstrated a loss of niche specificity (sinus vs. lung, P = .492).
      Two CF patients underwent lung transplantation at 4.5 and 9 months prior to
      sampling. Sinus and lung samples from these two patients demonstrated distinct
      microbial communities. CONCLUSIONS: Patients with CF undergoing surgery for CRS
      exhibit substantial bacterial community collapse in the sinuses and a loss of
      niche specificity between the upper and lower airways compared to non-CF patients
      with CRS. These results extend previous studies elucidating the lower airway
      microbiome in cystic fibrosis and provide support for the concept of microbial
      translocation in the cystic fibrosis airways. LEVEL OF EVIDENCE: 4. Laryngoscope,
      2018.

PMID- 30284280
TI  - Does an intrauterine exchange transfusion improve the fetal prognosis in
      parvovirus infection cases?
AB  - BACKGROUND: Almost 20% of parvovirus B19 foetal infections require intrauterine
      transfusions. In addition, myocardial dysfunction has been observed in severe
      parvovirus B19 infections. One objective of an intrauterine exchange transfusion
      (IUET) is to avoid an overload during the transfusion. Our aim was to study the
      obstetrical and neonatal outcomes in cases of IUETs performed for foetal
      parvovirus infections and to compare our survival rate to those studies in which
      simple in utero transfusions were chosen. STUDY DESIGN AND METHODS: This was a
      retrospective monocentre study of all patients followed up for parvovirus B19
      infections in which IUETs were performed. An IUET was indicated when foetal
      hydrops was observed and/or when severe foetal anaemia was diagnosed though an
      elevation in the middle cerebral artery peak systolic velocity. The
      characteristics of each pregnancy and the neonatal outcomes were studied until
      hospital discharge. RESULTS: Thirty-five IUETs were performed in 26 foetuses. The
      median gestational age of the first IUET was 22.6 weeks. Only one foetal
      bradycardia incidence was recorded during the procedure. Three medical pregnancy
      terminations were observed in our series, secondary to severe cerebral anomalies
      confirmed in the magnetic resonance imaging. Five in utero deaths occurred, in
      which 2 of the foetuses underwent multiple IUETs. All the neonates had normal
      haemoglobin levels at birth, and none were transferred to the neonatal intensive
      care unit. The overall survival rate was 70%. CONCLUSION: IUETs exhibit a
      survival rate similar to that of simple intrauterine transfusions in foetal
      parvovirus infection cases.

PMID- 30284281
TI  - In Response to pH-Neutralizing Esophageal Irrigations as a Novel Mitigation
      Strategy for Button Battery Injury.

PMID- 30284282
TI  - Floral uniformity through evolutionary time in a species-rich tree lineage.
AB  - Changes in floral morphology are expected across evolutionary time and are often
      promoted as important drivers in angiosperm diversification. Such a statement,
      however, is in contrast to empirical observations of species-rich lineages that
      show apparent conservative floral morphologies even under strong selective
      pressure to change from their environments. Here, we provide quantitative
      evidence for prolific speciation despite uniform floral morphology in a tropical
      species-rich tree lineage. We analyse floral disparity in the environmental and
      phylogenetic context of Myrcia (Myrtaceae), one of the most diverse and abundant
      tree genera in Neotropical biomes. Variation in floral morphology among Myrcia
      clades is exceptionally low, even among distantly related species. Discrete
      floral specialisations do occur, but these are few, present low phylogenetic
      signal, have no strong correlation with abiotic factors, and do not affect
      overall macroevolutionary dynamics in the lineage. Results show that floral form
      and function may be conserved over large evolutionary time scales even in
      environments full of opportunities for ecological interactions and niche
      specialisation. Species accumulation in diverse lineages with uniform flowers
      apparently does not result from shifts in pollination strategies, but from
      speciation mechanisms that involve other, nonfloral plant traits.

PMID- 30284283
TI  - Impact of Head and Neck Cancer Treatment on Survivors' Mealtime Experience.
AB  - OBJECTIVES/HYPOTHESIS: The objectives of the study were to develop a mealtime
      experience self-assessment questionnaire that was head and neck cancer (HNC)
      survivors-driven and based on the International Classification of Functioning,
      Disability and Health (ICF) framework, and to identify common mealtime issues
      reported by HNC survivors. STUDY DESIGN: Outcomes research. METHODS: Mealtime
      issues reported by HNC survivors in prior research was synthesized and classified
      using the ICF framework to develop the content and structure of the Head and Neck
      Cancer Survivors' Assessment of Mealtimes (HNSAM). A total of 122 HNC survivors
      completed both HNSAM and M.D. Anderson Dysphagia Inventory (MDADI) to assess for
      concurrent validity, whereas 51% of participants completed a second HNSAM for
      test-retest reliability. RESULTS: The HNSAM scores were significantly correlated
      with the MDADI scores. Dysphagic participants (n = 45) had significantly higher
      HNSAM scores than the nondysphagic participants (n = 77). Principal component
      analysis revealed three factors that matched with the HNSAM subscales. Good
      internal consistency (Cronbach's alpha = 0.72-0.96) and test-retest reliability
      (intraclass correlation = 0.76-0.91) were found. Both dysphagic and nondysphagic
      participants reported difficulties with saliva-related issues and were not able
      to enjoy food/drinks that they previously enjoyed. CONCLUSIONS: HNC survivors
      experience mealtime changes after cancer treatment. These initial validity data
      support the potential for the HNSAM to help HNC survivors' identify changes to
      the mealtime experience. Validation of the English version of the tool is now
      required. LEVEL OF EVIDENCE: 2c Laryngoscope, 2018.

PMID- 30284284
TI  - Voice Outcomes of Lipoinjection Versus Medialization Laryngoplasty for
      Nonparalytic Glottic Insufficiency.
AB  - OBJECTIVE: To compare voice outcomes of autogenous fat injection versus
      medialization laryngoplasty in patients with glottic insufficiency due to vocal
      fold paresis or atrophy. METHODS: A retrospective review was performed from 2009
      to 2017 of all patients who underwent lipoinjection or medialization
      laryngoplasty (ML) for glottic insufficiency. Charts were reviewed for
      demographic information, preoperative diagnosis, surgical intervention, Voice
      Handicap Index-10 (VHI-10) and Glottal Function Index (GFI) scores, follow-up
      time (minimum 3 months), and concomitant voice therapy. RESULTS: Eighty-three
      patients were initially identified and limited to 28 based on the
      inclusion/exclusion criteria. Thirty-five procedures were performed with a total
      of 15 fat injections and 20 MLs. The mean age was 60.7 years in the lipoinjection
      group and 55.6 years in the ML group. There was no significant difference in
      pretreatment VHI-10 scores between the two groups. Using the lowest recorded
      voice scores during the follow-up period, both groups had a significant decrease
      (P < 0.05) compared to preoperative scores (VHI-10: fat decreased from 27.8 to
      14.2, ML decreased from 30.5 to 9.1; GFI: fat decreased from 13.7 to 5.27, ML
      decreased from 13.6 to 4.6). When evaluating the entire follow-up period (median
      19 months in fat group, 16.3 months in ML), only the ML group maintained a
      significant improvement in VHI-10 (median delta 14.5) and GFI (median delta 7)
      compared to preoperative scores. CONCLUSION: Although both autogenous fat
      injection and ML result in improved voice scores in the short term, the effect of
      fat injection appears to be limited, as evidenced by worsening VHI-10 and GFI
      scores over time. LEVEL OF EVIDENCE: 4. Laryngoscope, 2018.

PMID- 30284285
TI  - Blood sample from an intraosseous device.

PMID- 30284286
TI  - Distribution of hepatitis A antibodies in US blood donors.
AB  - BACKGROUND: Recently, there has been an increase in the number of hepatitis A
      outbreaks in the United States. Although the presence of hepatitis A virus (HAV)
      RNA in blood donors is known to be low, HAV antibody prevalence in this
      population is unknown. STUDY DESIGN AND METHODS: Samples from 5001 US blood
      donors collected primarily in the midwestern United States in 2015 were tested
      for the presence of HAV IgG antibodies using chemiluminescent microparticle
      immunoassays on the ARCHITECT platform (Abbott Laboratories). RESULTS: The
      overall prevalence of IgG anti-HAV was 60%. Only one specimen was IgM anti-HAV
      positive, for an incidence of 0.02%. IgG anti-HAV prevalence among donors aged 16
      to 19 years was 67%, decreased to 54% among donors aged 40 to 49 years and
      increased to 70% among donors aged 80 to 93 years. No differences were seen by
      sex with overall IgG anti-HAV prevalence of 61% and 60% for males and females,
      respectively. Among the five states (Illinois, Indiana, Kansas, Kentucky, and
      Missouri) with the highest number of donors tested, IgG anti-HAV prevalence in
      Missouri (65%) was significantly higher (p <0.01) than that in Illinois (52%) or
      Kentucky (59%). No other significant differences between states were noted.
      CONCLUSION: This study demonstrates the overall high rates of IgG anti-HAV in US
      blood donors, with the low associated risk of HAV transfusion transmission likely
      the result of low incidence and effective vaccination.

PMID- 30284287
TI  - Four novel silenced RHCE.

PMID- 30284288
TI  - Long-term monitoring of virus antibody titers in human intravenous immunoglobulin
      lots derived from donors in Japan.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) contains immunoglobulin G against
      various viruses, except those that have been screened, such as human
      immunodeficiency and hepatitis C viruses. Antivirus titers reflect the serostatus
      of the blood donor population in the collection region and are of clinical
      interest. STUDY DESIGN AND METHODS: During the past 10 years, measles, mumps,
      rubella, varicella-zoster, hepatitis A and B, Epstein-Barr, and human respiratory
      syncytial viruses; human parainfluenza viruses 1, 2, and 3; human herpes simplex
      viruses 1 and 2; human herpesvirus 6; cytomegalovirus (CMV); human adenoviruses
      (HAdVs) 1, 2, 3, 7, and 11; human parvovirus B19; and human echovirus 9 and 11
      titers in IVIG lots have been measured by a commercial testing facility. A viral
      neutralizing assay for CMV has been used at our facility. Herein, we summarize
      the measurements and results of a regression analysis of the trends in virus
      antibody titers. RESULTS: IVIG lots contained significant titers against all of
      the above viruses, except for HAdV 7. Three patterns-stable, increasing, and
      decreasing-were observed, without any drastic changes. Although these trends
      reflect the seroprevalence in Japan, the titers were not obviously affected by
      the cycle of epidemics. On the other hand, the prevalence data suggest that
      titers against hepatitis A virus and other viruses will decrease in the near
      future, although they are currently stable. CONCLUSION: Monitoring the titer of
      IVIG lots and seroprevalence of donor populations is important for anticipating
      future changes in virus antibody titers of IVIG lots and can provide useful
      information of clinical interest.

PMID- 30284289
TI  - Alloimmunization risk associated with amino acid 223 substitution in the RhD
      protein: analysis in the light of molecular modeling.
AB  - BACKGROUND: Partial D status is a major concern for transfusion and pregnancy,
      due to the possibility of carriers becoming immunized. When known carriers of a D
      variant have never been exposed to complete D, they are assumed to have D partial
      status based on the position of the amino acid substituted. New approaches for
      predicting immunization risk are required. We built a three-dimensional (3D)
      structural model to investigate the consequences of substitutions of Amino Acid
      223 involved in a large number of D variants. STUDY DESIGN AND METHODS: Homology
      modeling was performed with multiple templates. The model was evaluated by
      comparing the interactions of the known p.Phe223Val variant (RHD*08.01) and a new
      p.Phe223Ser variant (RHD*52) to RhD reference allele (p.Phe223). The consequences
      predicted by modeling the variants were compared with serologic data. RESULTS:
      The 3D structural model was generated from two related protein structures and
      assessed with state-of-the-art approaches. An analysis of the interactions of the
      variant Residue 223 in the proposed 3D model highlighted the importance of this
      position. Modeling predictions were consistent with the serologic and clinical
      data obtained for the D antigen with a substitution of Amino Acid 223.
      CONCLUSION: We used a 3D structural model to evaluate the effect of the p.Phe223
      substitution on the conformation of the RhD protein. This model shed light on the
      influence of substitutions on the structure of the RhD protein and the associated
      alloimmunization risk. These initial findings indicate that the p.Phe223Ser
      variant can be considered partial.

PMID- 30284290
TI  - Secukinumab for treatment of psoriasis: does secukinumab precipitate or promote
      the presentation of cutaneous T-cell lymphoma?
AB  - Secukinumab is an interleukin (IL)-17 monoclonal antibody inhibiting T-helper
      (Th)1-mediated immune response. It has proven high efficacy for moderate to
      severe psoriasis but data on its long-term toxicities are limited. We describe
      two patients who received secukinumab for clinically presumed psoriasis, but were
      subsequently diagnosed with mycosis fungoides (MF) following skin biopsies
      triggered by skin deterioration while on secukinumab. Previous studies suggested
      decreased numbers of regulatory T cells (Tregs) with increasing stage of MF,
      which may lead to the shift in the Treg/Th17 balance towards the Th17 pathway.
      Theoretically, the use of IL-17 monoclonal antibodies to inhibit Th17 pathway may
      lead to further immunosuppression and disease progression in cutaneous T-cell
      lymphoma (CTCL) by shifting the balance towards Tregs, although this hypothesis
      has not been proven. With uncertainty over the role of IL-17 and Treg/Th17 as
      well as diagnostic challenges in CTCL, we recommend that patients should have a
      confirmatory skin biopsy prior to the commencement of biologic therapy.

PMID- 30284291
TI  - Diffusion Monte Carlo Calculations of Zero-Point Energies of Methanol and
      Deuterated Methanol.
AB  - Diffusion Monte Carlo (DMC) simulations have been used to obtain quantum zero
      point energies of methanol and all its isotopologs and isotopomers, using a new,
      accurate semi-global potential energy surface. This potential energy surface is a
      precise, permutationally invariant fit to 6676 ab initio energies, obtained at
      the CCSD(T)-F12b/aug-cc-pVDZ level of theory. Quantum zero-point energies of
      deuterated methanol isotopomers are very close to each other and so a simple
      statistical argument can be used to estimate the populations of each isotopomer
      at very low-temperatures. The DMC simulations also indicate that there is
      virtually zero probability for H/D exchange in the zero-point state.

PMID- 30284292
TI  - Switching the nature of catalytic centers in Pd/NHC systems by solvent effect
      driven non-classical R-NHC Coupling.
AB  - A well-established oxidative addition of organic halides (R-X) to N-heterocyclic
      carbene (NHC) complexes of palladium(0) leads to formation of (NHC)(R)PdII (X)L
      species, the key intermediates in a large variety of synthetically useful cross
      coupling reactions. Typical consideration of the cross-coupling catalytic cycle
      is based on the assumption of intrinsic stability of these species, where the
      subsequent steps involve coordination of the second reacting partner. Thus, high
      stability of the intermediate (NHC)(R)PdII (X)L species is usually taken for
      granted. In the present study it is discussed that such intermediates are prone
      to non-classical R-NHC intramolecular coupling process (R = Me, Ph, Vinyl,
      Ethynyl) that results in removal of NHC ligand and generation of another type of
      Pd catalytic system. DFT calculations (BP86, TPSS, PBE1PBE, B3LYP, M06, wB97X-D)
      clearly show that outcome of R-NHC coupling process is not only determined by
      chemical nature of the organic substituent R, but also strongly depends on the
      type of solvent. The reaction is most favorable in polar solvents, whereas the
      non-polar solvents render the products less stable. (c) 2019 Wiley Periodicals,
      Inc.

PMID- 30284293
TI  - Simulations of NaCl Aggregation from Solution: Solvent Determines Topography of
      Free Energy Landscape.
AB  - The partition-enabled analysis of cluster histograms (PEACH) method is used to
      calculate the free energy surface of NaCl aggregation using cluster statistics
      from MD simulations of small systems (40-90 ions plus solvent) in four solvents.
      In all cases (pure methanol, pure water, and two methanol/water mixtures) NaCl
      clusters show a transition from amorphous to rocksalt structure with increasing
      cluster size. The crossover sizes, and the apparent kinetic barrier to ordering,
      increase with increasing water content. Implications for the proposed two-step
      mechanism of NaCl crystal nucleation (in which the ordered structure emerges from
      a large disordered cluster), and how this mechanism might depend on solvent and
      on degree of supersaturation, are discussed. In pure water, nonideal crowding
      effects that promote clustering are identified from systematic concentration
      dependent deviations between simulation results and the PEACH model fit. In
      contrast, the ability of PEACH to fit aggregation statistics in mixed solvents is
      consistent with negligible interactions between ions in different clusters. (c)
      2018 Wiley Periodicals, Inc.

PMID- 30284294
TI  - Reduction of OH vibrational frequencies in amino acids by positron attachment.
AB  - Positron affinities have been calculated for five amino acid molecules
      (asparagine, cysteine, glycine, proline, and serine) with the intramolecular
      ?COOH...NH2 ? hydrogen-bonded motif as a function of the OH distance using two
      computational methods, namely multicomponent molecular orbital theory and
      pseudopotential model. Since the elongation of the carboxylic OH bond leads to
      the formation of highly polarized zwitterionic amino acid with ?COO- ...NH3 + ?
      structure, the calculated positron affinity significantly increases with the
      elongation of the OH distance. This indicates that the OH bond strength is
      significantly weakened by positron attachment. We discuss the reduction of OH
      vibrational frequencies using effective one-dimensional potential energy curves
      for neutral and positron-attached amino acid molecules. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30284295
TI  - Attraction between electrophilic caps: A counterintuitive case of noncovalent
      interactions.
AB  - Intermolecular attractive interaction between electrophilic sites is a
      counterintuitive phenomenon, as the electrostatic interaction therein is
      repulsive and destabilizing. Here, we confirm this phenomenon in four
      representative complexes, using state-of-the-art quantum mechanical methods. By
      employing the block-localized wavefunction (BLW) method, which can turn off
      intermolecular charge transfer interactions, we profoundly demonstrated the
      significance of charge transfer interactions in these seemingly counterintuitive
      complexes. Indeed, after being "turned off" the intermolecular charge transfer
      interaction in, for example, the FNSi...BrF complex, the originally attractive
      intermolecular interaction turns to be repulsive. The energy decomposition
      approach based on the BLW method (BLW-ED) can partition the overall stability
      gained on the formation of intermolecular noncovalent interaction into several
      physically meaningful components. According to the BLW-ED analysis, the
      electrostatic repulsion in these counterintuitive cases is overwhelmed by the
      stabilizing polarization, dispersion interaction, and most importantly, the
      charge transfer interaction, resulting in the eventual counterintuitive overall
      attraction. The present study suggests that, predicting bonding sites of
      noncovalent interactions using only the "hole" concept may be not universally
      sufficient, because other significant stabilizing factors will contribute to the
      stability and sometimes, play even bigger roles than the electrostatic
      interaction and consequently govern the complex structures. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30284296
TI  - Mechanistic insight on water and substrate catalyzed the synthesis of 3-(1H-indol
      3-yl)-2-(4-methoxybenzyl)isoindolin-1-one: Driving by noncovalent interactions.
AB  - The mechanisms of the synthesis of 2-substituted-3-(1H-indol-3-yl)-isoindolin-1
      one derivatives have been investigated theoretically under unassisted, self
      assisted, and water-assisted conditions. Being different from previously proposed
      catalyst-free by Hu et al., our results show that the title mechanism can be
      altered and accelerated by solvent and substrate 2. Two types of mechanisms have
      been developed by DFT calculations differ in the reaction sequence of substrates
      1 with 3 (M1) or 2 (M2) followed by 2 (M1) or 3 (M2), and water-assisted M1 is
      the most favored one. It was found that the nucleophilicity of substrate 3 is
      stronger than that of 2. Our calculations suggest that the water-assisted pathway
      in M1 is the most favorable case, which undergoes nucleophilic addition and H
      shift, C-N bond formation and water elimination, and intramolecular cyclization
      and water elimination. The rate-determining step is the nucleophilic attack
      process. Moreover, we also explored the effect of nucleophilic attack of the
      nitrogen of (4-methoxyphenyl)methanamine on hydroxyl or carbonyl group carbon of
      phthalaldehydic acid on the activation energy. More importantly, we found that
      water molecules play a critical role in the whole reaction, not only act as
      solvent but also as an efficient catalyst, proton shuttle, and stabilizer to
      stabilize the structures of transition states and intermediates via pi...H-O,
      O...H-N, O...H-C, and O...H-O interactions. The origin of the different
      reactivity of M1 and M2 is ascribed to the pivotal noncovalent interactions exist
      between catalyst (water and substrate 2) and reactants. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30284297
TI  - Guideline-directed statin intensification in patients with new or worsening
      symptoms of peripheral artery disease.
AB  - BACKGROUND: The ACC/AHA cholesterol guidelines recommend patients with peripheral
      artery disease (PAD) be treated with a moderate to high-intensity statin. The
      extent to which patients with new or worsening PAD symptoms are offered guideline
      therapy is unknown. HYPOTHESIS: There is significant variability in rate of
      guideline-directed statin intensification across clinical practices. METHODS: In
      the PORTRAIT registry, patterns of statin therapy were assessed in 1144 patients
      at 16 PAD specialty clinics between June 2011 and December 2015 before and after
      an evaluation for new or worsening claudication symptoms. We documented whether
      patients were treated with a guideline statin as well as the incidence of statin
      intensification. Statin intensification was defined as transitioning from no
      statin or low-intensity statin to moderate or high-intensity statin treatment.
      Patient factors associated with intensification were examined. Site and provider
      level variation in intensification was summarized using an adjusted median odds
      ratio (aMOR). RESULTS: Among 1144 patients, 810 (70.8%) were initially on
      guideline therapy compared to 334 (29.2%) that were not. In the latter, 103
      (30.8%) received intensification following evaluation. Patients with typical
      symptoms displayed greater odds of intensification (OR 3.74; 95% CI: 1.23-11.41)
      while older patients had lower odds of intensification (OR 0.60/decade; 95% CI:
      0.41-0.88). Site variability for statin intensification was observed across sites
      (aMOR = 3.15; 95% CI 1.22-9.60, [P = 0.02]) but not providers (aMOR = 1.89; 95%
      CI 1.00-3.90, [P = 0.14]). CONCLUSIONS: Most patients evaluated at a PAD
      specialty clinic for new or worsening claudication symptoms arrived on guideline
      statin therapy. Only 31% not receiving appropriate therapy underwent statin
      intensification. These findings highlight an important opportunity to optimize
      medical therapy for patients with PAD.

PMID- 30284298
TI  - Neprilysin levels at the acute phase of ST-elevation myocardial infarction.
AB  - BACKGROUND: Several preliminary analyses suggested an association between
      neprilysin levels and myocardial infarction. HYPOTHESIS: The objective was to
      assess whether Neprilysin (NEP) plasma levels following reperfusion might be a
      surrogate for infarct size (IS) or predict adverse outcomes in acute ST-segment
      elevation myocardial infarction (STEMI) patients. METHODS: We measured NEP levels
      in a prospective cohort of 203 patients with STEMI referred for primary
      percutaneous coronary intervention. Circulating soluble NEP was measured by ELISA
      at admission (t0) and four hours later (t4) following reperfusion and on 7 times
      points (t0, t4, t12, t24, t48, day 7 and day 30) in a subset of 21 patients.
      Infarct size (IS) and left ejection fraction (LVEF) were measured at one month by
      cardiac magnetic resonance (CMR). Adverse cardiovascular outcomes were collected
      at 12-month follow-up. RESULTS: Median t0 and t4 NEP levels in 203 patients were
      respectively 88.3 pg/mL (IQR [14; 375.4]) and 101.5 pg/mL (IQR [18.5; 423.8]).
      These levels remained unchanged over one month (p=0.70). NEP levels did not
      correlate significantly with IS (p=0.51) or LVEF (p=0.34). There was no
      correlation between NEP and troponin, creatine kinase and interleukin-6 levels at
      h0 and h4. NEP levels above the median were not associated with adverse outcomes
      at follow-up (HR= 1.28, 95%CI [0.69; 2.37]; p=0.42). CONCLUSIONS: NEP serum
      levels were widely distributed and did not change significantly in the first
      hours and one-month period following reperfusion in STEMI patients. There was no
      significant relationship with markers of infarct size and inflammation, and one
      year adverse outcomes.

PMID- 30284299
TI  - Evaluation of cystatin C and neutrophil gelatinase-associated lipocalin as
      predictors of mortality in patients undergoing percutaneous mitral valve repair
      (MitraClip).
AB  - BACKGROUND: Compromised renal function is a major risk factor that is strongly
      associated with poor outcome in patients with mitral regurgitation (MR) and heart
      failure. Cystatin C, a cysteine protease inhibitor, has been used as a specific
      and sensitive biomarker of renal function. Neutrophil gelatinase-associated
      lipocalin (NGAL) is another sensitive biomarker that specifically indicates
      functional and structural kidney damage. The aim of the present study was to
      determine the predictive value of serum cystatin C and urinary NGAL as indicators
      of mortality in patients undergoing percutaneous mitral valve repair (PMVR).
      METHODS: A total of 120 consecutive patients (age: 77.3 years [+/-11.2])
      undergoing PMVR using the MitraClip system were included in this study. Venous
      blood and urinary samples were collected for biomarker analysis prior to PMVR.
      Physiological parameters, medication use, safety events, and all-cause mortality
      were assessed 12 months after the procedure. RESULTS: Twelve months after PMVR,
      there was a significant reduction in the severity of MR (P < 0.001), and an
      improvement in the New York Heart Association class (P < 0.01) was documented.
      Baseline levels of serum cystatin C (nonsurvivors: 2.4 mg/L [interquartile, IQR:
      1.7;3.1] vs survivors: 1.7 mg/L [IQR: 1,3;2.1], P < 0.001) and urinary NGAL
      (nonsurvivors: 242.0 ng/mL [IQR: 154.5;281.5] vs survivors: 132.0 ng/mL
      [IQR:107.0;177.3], P < 0.001) were significantly higher in patients who died
      during the 12-month follow-up period. CONCLUSION: Cystatin C and urinary NGAL
      were found to be predictors of long-term mortality in high-risk patients
      undergoing PMVR. Thus, cystatin C and NGAL assessment may be helpful in risk
      stratification in patients undergoing PMVR.

PMID- 30284301
TI  - Impact of Atrial Fibrillation on patients hospitalized for Acute Myocarditis:
      Insights from a nationally-representative United States cohort.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with increased all-cause
      mortality in the general population. However, the impact of atrial fibrillation
      on the in-hospital outcomes of acute myocarditis patients is not well
      characterized. METHODS: Patients (age >=18 years) with a primary diagnosis of
      acute myocarditis in the National Inpatient Sample (NIS) from 2007 to 2014 were
      included, using the ICD-9-CM diagnostic codes. We compared the in-hospital
      outcomes between the AF group and propensity score-matched control group without
      AF. RESULTS: AF was reported in 602 (9%) of the acute myocarditis patients.
      Compared to those without AF, acute myocarditis patients with AF experienced
      higher in-hospital mortality (odds ratio [OR] 1.7, 95% CI 1.1 to 2.7, p = 0.02).
      AF was associated with higher risk of cardiogenic shock (OR 1.9, 95% CI 1.3 to
      2.8, p < 0.001), cardiac tamponade (OR 5.6, 95% CI 1.2 to 25.3, p = 0.002) and
      acute kidney injury (1.6, 95% CI 1.1 to 2.1, p = 0.02). Furthermore, patients
      with AF were more likely to have non-routine hospital discharge (31.6% Vs. 38.4%
      p = 0.02), longer length of stay and higher cost of hospitalization. CONCLUSIONS:
      AF was associated with increased risk of in-hospital mortality and complications
      in patients admitted to the hospital with acute myocarditis.

PMID- 30284300
TI  - Calculations on 1,8-naphthoquinone predict that the ground state of this
      diradical is a singlet.
AB  - (12/12)CASPT2, (16/14)CASPT2, B3LYP, and CCSD(T) calculations have been carried
      out on 1,8-Naphthoquinone (1,8-NQ), to predict the low-lying electronic states
      and their relative energies in this non-Kekule quinone diradical. CASPT2 predicts
      a 1 A1 ground state, with three other electronic states-3 B2 , 3 B1 , and 1 B1 
      within about 10 kcal/mol of the ground state in energy. On the basis of the
      results of these calculations, it is predicted that NIPES experiments on 1,8-NQ *
      will find that 1,8-NQ is a diradical with a singlet ground state. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30284302
TI  - A paired trial comparing mononuclear cell collection in two machines for further
      inactivation through an inline or offline extracorporeal photopheresis procedure.
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) is an effective treatment.
      However, protocols differ widely, and some questions, such as the number of cells
      to be collected or the number of ECP treatment days per treatment cycle, are
      still unsolved. The aim of this study was to compare a multistep (offline)
      (Spectra Optia and Macogenic G2) against an integrated (inline) ECP system
      (Therakos Cellex system) with respect to mononuclear cell (MNC) collection. STUDY
      DESIGN AND METHODS: The number and quality parameters of the MNC products
      collected were evaluated together with some machine parameters, such as
      collection time. Comparisons were made through paired sample analysis with the t
      test. RESULTS: Fourteen patients underwent 15 double-paired procedures using both
      ECP protocols. The average MNC collected in the multistep procedure was 77.4 *
      108 , four times more than in the integrated procedure (18.5 * 108 ). MNC purity
      (84.4% vs. 63.8%) and enrichment (27.9 vs. 5.9) in the product collected were
      also higher in the multistep procedure. The whole ECP time was higher in the
      multistep than in the integrated procedure (272 vs. 106 min), but the calculated
      time to collect 25 * 108 MNCs in the multistep was shorter compared with the one
      step procedure (77.8 vs. 172 min). All these differences between the two
      protocols were statistically significant. CONCLUSIONS: These two ECP protocols
      are different with respect to MNC collection and length of procedure. Some
      unresolved questions, such as the better MNC dose to inactivate or the number of
      consecutive days that ECP should be performed for optimal clinical efficacy,
      require further review.

PMID- 30284303
TI  - A variant RhAG protein encoded by the RHAG*572A allele causes serological weak D
      expression while maintaining normal RhCE phenotypes.
AB  - BACKGROUND: The molecular events resulting in a weak D phenotype include missense
      mutations, in-frame insertion, or deletion mutations of the RHD gene and hybrid
      RHD-CE-D hybrid alleles. Mutations in genes encoding the proteins that are
      required for proper membrane expression of Rh proteins, such as RhAG and ankyrin
      1, can lead to absent or weakened expression of Rh antigens. STUDY DESIGN AND
      METHODS: Blood sample from a Chinese blood donor with a serological weak D
      phenotype was collected. RhAG antigen expression, RhD, and RhCE phenotypes were
      determined. Analysis of the RHD and RHCE genotypes by RH multiplex ligation
      dependent probe amplification (MLPA), Sanger sequencing of the RHD exons, and
      next-generation sequencing (NGS) of the RHAG and ANK1 exons were performed.
      Expression studies in vitro were conducted by lentivirally transducing the mutant
      RHAG*572A or wild-type RHAG, in combination with either RHD or RHCE constructs,
      into HEK 293 T cells. The expression of RhAG, RhD, and RhCE antigens was analyzed
      by flow cytometry. RESULTS: Serological weak D and normal C + c- E- e +
      phenotypes, normal CCDDee genotype determined by RH-MLPA, and normal sequence of
      the RHD gene by Sanger sequencing were demonstrated. A homozygous variant (c.572G
      > A, p.Arg191Gln) of the RHAG gene was revealed by NGS analysis. Normal RhAG,
      weak RhD, and normal RhCE antigens were detected in cells transduced with the
      mutant RHAG*572A, the mutant RHAG*572A and RHD, and the mutant RHAG*572A and RHCE
      constructs, respectively. CONCLUSION: The homozygous presence of RHAG*572A allele
      results in weak D expression. It does not affect RhCE expression.

PMID- 30284304
TI  - Turning the simulation session upside down: the supervisor plays the resident.

PMID- 30284306
TI  - A bulk adjusted linear combination of atomic orbitals (BA-LCAO) approach for
      nanoparticles.
AB  - We describe a bulk adjusted linear combination of atomic orbitals (BA-LCAO)
      approach for nanoparticles. In this method, we apply a many-body scaling function
      (in similar manner as in the environment-modified total energy based tight
      binding method) to the DFT-derived diatomic AO interaction potentials (like in
      the conventional orbital-based density-functional tight binding approach)
      strictly according to atomic valences acquired naturally in a bulk structure.
      This modification, (a) facilitates all atom orbital-based electronic structure
      calculations of charge carrier dynamics in nanoscale structures with a molecular
      acceptor, and (b) allows to closely match high-level density functional
      calculation data (previously adjusted to the available experimental findings) for
      bulk structures. To advance practical application of the BA-LCAO approach we
      parameterize the Hamiltonian of wurtzite CdSe by fitting its band structure to a
      high-level DFT reference, corrected for experimentally measured band edges. Here,
      unlike in conventional DFTB approach, we: (1) use hydrogen-like AOs for the basis
      as exact atomic eigenfunctions, while orbital energies of which are taken from
      experimentally measured ionization potentials, and (2) parameterize the many-body
      scaling functions rather than the atomic wavefunctions. Development of this
      approach and parameters is guided by our goals to devise a method capable of
      simultaneously treating the problems of (i) interfacial electron/hole transfer
      between finite, variable size nanoparticles and electron scavenging molecules,
      and (ii) high-energy electronic transitions (Auger transitions) that mediate
      multi-exciton decay in quantum dots. Electronic structure results are described
      for CdSe quantum dots of various sizes. (c) 2018 Wiley Periodicals, Inc.

PMID- 30284305
TI  - Comparison of adiposity indices in relation to prehypertension by age and gender:
      A community-based survey in Henan, China.
AB  - BACKGROUND: To compare the efficiency of bioelectrical indices (visceral fat
      index [VFI], percentage body fat [PBF]) and anthropometric indices (body mass
      index, waist circumference, waist-to-height ratio, a body shape index ) in the
      relation to prehypertension (120-139/80-89 mm Hg) among the Chinese population.
      METHODS: Using stratified multistage random sampling method, a general population
      based sample of 11 175 adults in Henan province were selected from 2013 to 2015.
      The individuals were divided into three categories by blood pressure levels:
      normotension (<120 and 80 mm Hg), stage 1 prehypertension (120-129/80-84 mm Hg)
      and stage 2 prehypertension (130-139/85-89 mm Hg). RESULTS: VFI and PBF tended to
      increase with age in men and women. However, for each age-specific group, men
      tended to have higher VFI than women (all P < 0.01) and women tended to have
      greater PBF (all P < 0.0001). The odds ratios (OR) and area under the receiver
      operating characteristic curves for prehypertension associated with adiposity
      indices declined with age. VFI and PBF showed higher standardized adjusted ORs
      for prehypertension in young (~40 years) men (VFI: 2.02-3.05; PBF: 1.82-2.80) and
      young women (VFI: 1.90-2.58; PBF:1.70-2.29). Moreover, based on Youden's index,
      VFI and PBF exhibited the superiority for identifying prehypertension in men
      (0.20-0.32) and women (0.31-0.39), respectively. CONCLUSION: In summary, there
      was stronger association of VFI and PBF with prehypertension in men than in
      women, respectively, especially for young adults.

PMID- 30284307
TI  - Contrast-Enhanced Ultrasound With Perflubutane for Sentinel Lymph Node Mapping in
      Cutaneous Melanoma: A Pilot Study.
AB  - OBJECTIVE: To study the feasibility of contrast-enhanced ultrasound (CEUS) for
      identification of SLN associated with cutaneous melanoma. STUDY DESIGN: Single
      arm pilot study in a swine animal model. METHODS: One milliliter of perflubutane
      (Sonazoid, GE Healthcare, Milwaukee, WI) was injected into the peritumoral dermis
      in five swine with cutaneous melanoma. Ultrasonography was used to follow
      enhancing lymphatic channels to lymph nodes (LN). Intradermal injection of vital
      blue (VB) dye was used as a positive control. LN identified by either method were
      excised and examined histologically. RESULTS: There were five primary cutaneous
      melanomas with mean area of 4.36 +/- 4.75 cm2 and Breslow depth of 3.6 +/- 1.5
      mm. Six possible sentinel lymph node (SLN)s were identified with CEUS, and nine
      were identified with VB. SLN averaged 12.44 +/- 6.15 cm from the primary tumor.
      Four of six (67%) SLNs identified by CEUS and four of nine (44%) candidate SLNs
      identified by VB contained histologically confirmed metastatic melanoma. All six
      CEUS-identified SLNs were also identified with VB. Two LNs not containing
      melanoma were identified by CEUS; three were identified with VB. In all SLN with
      metastases, metastatic cells were scattered throughout the LN and not clustered
      in a discrete mass. CONCLUSION: CEUS with perflubutane feasibly identifies SLN
      associated with cutaneous melanoma and may be a useful adjunct technology in
      facilitating precise SLN dissection. Our work supports a clinical trial
      investigating the use of CEUS for this application. LEVEL OF EVIDENCE: NA.
      Laryngoscope, 2018.

PMID- 30284308
TI  - Exploration of Carbon Allotropes with Four-membered Ring Structures on Quantum
      Chemical Potential Energy Surfaces.
AB  - The existence of a new carbon allotrope family with four-membered rings as a key
      unit has been recently predicted with quantum chemical calculations. This family
      includes carbon allotropes in prism-, polymerized prism-, sheet-, tube-, and wavy
      forms. An atypical bond property has been observed in this series of carbon
      structures, which differs from the typical sp3 , sp2 , and sp hybridizations. The
      lowest energy barrier from some of the equilibrium states of the carbon
      structures has been determined with the SHS-ADDF (scaled-hypersphere-search
      combined with the anharmonic downward distortion following) method within the
      GRRM software program package. The height of the barriers indicates that the well
      is deep enough for the carbon structures to exist. This class of carbon
      allotropes is expected to be energy-reservoirs with extra energy of 100-350 kJ
      mol-1 per one carbon atom. This article presents the structures, energies and
      reactivity of the carbon allotropes with four-membered ring structures as well as
      the background of the findings in the context of the global exploration of
      potential energy surfaces. (c) 2018 Wiley Periodicals, Inc.

PMID- 30284310
TI  - Trichoderma mediate early and enhanced lignifications in chickpea during Fusarium
      oxysporum f. sp. ciceris infection.
AB  - Lignifications in secondary cell walls play a significant role in defense
      mechanisms of plants against the invading pathogens. In the present study, we
      investigated Trichoderma strain specific lignifications in chickpea plants pre
      treated with 10 potential Trichoderma strains and subsequently challenged with
      the wilt pathogen Fusarium oxysporum f. sp. ciceris (Foc). Trichoderma-induced
      lignifications in chickpea were observed through histochemical staining and
      expression of some genes of the lignin biosynthetic pathway. Lignifications were
      observed in transverse sections of shoots near the soil line through
      histochemical staining and expression pattern of the target genes was observed in
      root tissues through semi quantitative RT-PCR at different time intervals after
      inoculation of F. oxysporum f. sp. ciceris. Lignin deposition and expression
      pattern of the target genes were variable in each treatment. Lignifications were
      enhanced in all 10 Trichoderma strain treated and F. oxysporum f. sp. ciceris
      challenged chickpea plants. However, four Trichoderma strains viz., T-42, MV-41,
      DFL, and RO, triggered significantly high lignifications compared to the other
      six strains. Time course studies showed that effective Trichoderma isolates
      induced lignifications very early compared to the other strains and the process
      of lignifications nearly completes within 6 days of pathogen challenge. Thus,
      from the results it can be concluded that effective Trichoderma strains trigger
      lignifications very early in chickpea under Foc challenge and provide better
      protection to chickpea plants.

PMID- 30284309
TI  - Characterization of a novel bacteriophage specific to Exiguobacterium indicum
      isolated from a plateau eutrophic lake.
AB  - Exiguobacterium is a versatile genus with potential in industry and agriculture.
      No bacteriophage that infects Exiguobacterium has been reported, despite its
      potential impacts on the utilization of Exiguobacterium. E. indicum EI9 was
      isolated from Dianchi Lake, a plateau eutrophic lake in China, which can
      significantly inhibit the growth of Microcystis aeruginosa. To isolate and
      characterize Exiguobacterium-infecting bacteriophage, a virulent bacteriophage,
      DCEIV-9 that specifically infects E. indicum EI9 was isolated from Dianchi lake
      water sample. DCEIV-9 produced tiny, round, and clear plaques with 0.5-1 mm in
      diameter. Electron microscopy showed that DCEIV-9 is a typical representative of
      the Siphoviridae, with an icosahedral head (56 nm in diameter) and a non
      contractile tail (163 nm in length). Based on a one-step growth curve, latent
      period of 20 min and burst size of 51 PFU/infected cell were determined. DCEIV-9
      was sensitive to temperature over 50  degrees C and prefers acid environment.
      DCEIV-9 was extremely sensitive to proteinase K, chloroform, ethanol, Triton X
      100 but not sensitive to SDS. Restriction endonucleases analysis indicated that
      DCEIV-9 is a dsDNA virus. DCEIV-9 can only infect E. indicum, indicates that it
      has a narrow host range. DCEIV-9 is a potential new species.

PMID- 30284311
TI  - PyDEF 2.0: An Easy to Use Post-treatment Software for Publishable Charts
      Featuring a Graphical User Interface.
AB  - Herein we present an open-source program automating the post-treatment of solid
      state ab initio calculations performed with VASP, the most used solid-state
      simulation package. The program plots Density of States (DOS) and Band Diagrams,
      enabling the user to conduct efficiently a detailed study of electronic
      properties of a material. Our tool includes a complete module dedicated to point
      defects studies, proposing various corrections which can be activated at will and
      innovative property calculations such as defect concentrations. This is the first
      program of its kind to offer a direct plot of the stability domain of the studied
      matrix with respect to its components' chemical potentials. We also implemented
      the retrieval of optical indices E1 and E2 , the computation of the refractive
      and extinction coefficients (n, k) and the reflexivity R of the material. All
      features of the piece of software are available through a thoroughly designed
      user-friendly, elegant and efficient Graphical User Interface (GUI) to be
      accessible to material scientists with various expertises, from both the
      experimental and theoretical sides. All figures are of publishable quality and
      can be customized as desired. (c) 2018 Wiley Periodicals, Inc.

PMID- 30284313
TI  - Cost-benefit analysis of investment in occupational health and safety in
      Colombian companies.
AB  - OBJECTIVE: To determine whether investment in preventive measures by a Colombian
      insurer reduces rates of work-related injuries and results in positive returns
      from these investments. METHODS: The study is based on monthly panel data of 2011
      2015 of 303 medium and large companies affiliated with a private insurer in
      Colombia. We undertook regression modeling analysis to assess the effectiveness
      of incremental investments in occupational health and safety (OHS) prevention
      measures. The cost-benefit analysis is from the insurer's perspective. RESULTS:
      Investment in OHS per full-time equivalent was statistically significant at the
      1% level. We estimated that 4919 injuries were averted through these investments,
      resulting in the avoidance of $3 949 957 in costs. Our results suggest that the
      investments were worth undertaking from the insurer's perspective. CONCLUSIONS:
      This paper provides new empirical evidence on the effectiveness and cost-benefit
      of OHS investments in a middle-income country. Incremental investment in OHS can
      be effective and cost-beneficial.

PMID- 30284312
TI  - Two weeks of high-fat feeding disturb lipid and cholesterol molecular markers.
AB  - Metabolic disorders are often associated with liver steatosis and increased
      plasma cholesterol levels. However, the link between excessive lipid accumulation
      and impairments in cholesterol metabolism remains uninvestigated in the liver.
      Short term of high-fat diet (HFD) was previously shown to promote excessive lipid
      accumulation prior to the development of metabolic disorders. The present study
      intended to characterize how increases in liver fat alter the expression of
      several key regulators of hepatic cholesterol metabolism in response to a short
      term HFD. Wistar rats were randomly submitted either to HFD (n = 8) or a regular
      chow diet (n = 8) for 14 days. Increases in triglycerides were highly significant
      (P < 0.01) in the liver but marginal in the plasma of HFD rats. In contrast, the
      HFD resulted in higher (P < 0.01) cholesterol levels in plasma but not in liver
      samples. Gene expression of key markers involved in cholesterol uptake (LDL
      particles) including low-density lipoprotein receptor-related protein-1 (LRP-1)
      and protein convertase subtilisin/kexin type 9 (PCSK9) along with ATP-binding
      cassette, superfamily G, member 5 (ABCG5) involved in cholesterol exportation via
      bile ducts was found to be higher (P < 0.05) in response to the HFD. In contrast,
      expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), involved in
      cholesterol synthesis, was downregulated in the liver. The data support the
      concept that excessive accumulation of lipids promptly alters the expression of
      key genes regulating cholesterol metabolism in the liver. On a clinical point of
      view, this indicates that increases in plasma cholesterol occur after a short
      term HFD.

PMID- 30284314
TI  - Meta-analysis of non-linear exposure-outcome relationships using individual
      participant data: A comparison of two methods.
AB  - Non-linear exposure-outcome relationships such as between body mass index (BMI)
      and mortality are common. They are best explored as continuous functions using
      individual participant data from multiple studies. We explore two two-stage
      methods for meta-analysis of such relationships, where the confounder-adjusted
      relationship is first estimated in a non-linear regression model in each study,
      then combined across studies. The "metacurve" approach combines the estimated
      curves using multiple meta-analyses of the relative effect between a given
      exposure level and a reference level. The "mvmeta" approach combines the
      estimated model parameters in a single multivariate meta-analysis. Both methods
      allow the exposure-outcome relationship to differ across studies. Using
      theoretical arguments, we show that the methods differ most when covariate
      distributions differ across studies; using simulated data, we show that mvmeta
      gains precision but metacurve is more robust to model mis-specification. We then
      compare the two methods using data from the Emerging Risk Factors Collaboration
      on BMI, coronary heart disease events, and all-cause mortality (>80 cohorts, >18
      000 events). For each outcome, we model BMI using fractional polynomials of
      degree 2 in each study, with adjustment for confounders. For metacurve, the
      powers defining the fractional polynomials may be study-specific or common across
      studies. For coronary heart disease, metacurve with common powers and mvmeta
      correctly identify a small increase in risk in the lowest levels of BMI, but
      metacurve with study-specific powers does not. For all-cause mortality, all
      methods identify a steep U-shape. The metacurve and mvmeta methods perform well
      in combining complex exposure-disease relationships across studies.

PMID- 30284315
TI  - Dermatophytosis of the diaper area: Case report and literature review.
AB  - Dermatophytosis in infants is rare, especially dermatophytosis of the diaper
      area. This case report and literature review provides keys to establishing the
      above diagnosis and discusses the current controversies concerning the use of
      antifungal drugs in this age group.

PMID- 30284316
TI  - Effects of dietary amino acid supplementation on measures of whole-body and
      muscle protein metabolism in aged horses.
AB  - The objective of this study was to examine markers of whole-body and muscle
      protein metabolism in aged horses fed a diet typical for North American aged
      horses, supplemented with amino acids. In a replicated Latin square design, six
      aged horses (20 +/- 1.1 years) were studied while receiving each of three
      isocaloric, isonitrogenous diets, a control treatment concentrate (CON; 100 mg/kg
      1 BW day-1 lysine, 84 mg kg-1  day-1 threonine, 51 mg kg-1  day-1 methionine),
      LYS/THR (134 mg kg-1 BW day-1 lysine, 110 mg kg-1 BW day-1 threonine, 52 mg kg-1
      BW day-1 methionine) and LYS/THR/MET (132 mg kg-1 BW day-1 lysine, 112 mg kg-1 BW
      day-1 threonine, 62 mg kg-1 BW day-1 methionine). In each 15-days period, urine
      and faeces were collected for assessment of nitrogen balance. Blood samples were
      collected before and after feeding for analysis of plasma urea nitrogen (PUN),
      glucose, insulin and plasma amino acid concentrations. Skeletal muscle samples
      were collected for measurement of proteins associated with muscle protein
      synthesis and degradation, and horses underwent stable isotope infusion
      procedures for comparison of differences in whole-body rates of protein synthesis
      and degradation. There was no effect of treatment on relative abundance of
      proteins involved in protein synthesis, nitrogen retention or phenylalanine
      kinetics. PUN concentrations tended to be higher for LYS/THR (p = 0.054) and were
      higher for LYS/THR/MET (p = 0.0056) than for CON. Atrogin-1 abundance tended to
      be higher in the post-absorptive state for the CON treatment (p = 0.07),
      indicating that amino acid supplementation resulted in less muscle protein
      degradation when horses were in the post-absorptive state. However, lack of
      differences in nitrogen retention and phenylalanine kinetics indicated that whole
      body protein metabolism was not improved, and higher PUN concentrations in the
      supplemented diets suggest that the supplemented amino acids may have been
      catabolized. Amino acid availability was not limiting protein synthesis in the
      sedentary aged horses in this study when fed the CON diet.

PMID- 30284317
TI  - Uranium transfer and accumulation in organs of Danio rerio after waterborne
      exposure alone or combined with diet-borne exposure.
AB  - Uranium (U) toxicity patterns for fish have been mainly determined under
      laboratory-controlled waterborne exposure conditions. Because fish can take up
      metals from water and diet under in situ exposure conditions, a waterborne U
      exposure experiment (20 MUg L-1 , 20 d) was conducted in the laboratory to
      investigate transfer efficiency and target organ distribution in zebrafish Danio
      rerio compared with combined waterborne exposure (20 MUg L-1 ) and diet-borne
      exposure (10.7 MUg g-1 ). 233 Uranium was used as a specific U isotope tracer for
      diet-borne exposure. Bioaccumulation was examined in the gills, liver, kidneys,
      intestine, and gonads of D. rerio. Concentrations in the organs after waterborne
      exposure were approximately 500 ng g-1 fresh weight, except in the intestine (>
      10 MUg g-1 fresh wt) and the kidneys (200 ng g-1 fresh wt). No significant
      difference was observed between waterborne and diet-borne conditions. Trophic U
      transfer in organs was found but at a low level (< 10 ng g-1 fresh wt).
      Surprisingly, the intestine appeared to be the main target organ after both
      tested exposure modalities. The gonads (57% at 20 d) and the liver (41% at 20 d)
      showed the highest accumulated relative U burdens. Environ Toxicol Chem
      2018;9999:1-9. (c) 2018 SETAC.

PMID- 30284318
TI  - Evaluation of the DGT technique for predicting uptake of metal mixtures by
      fathead minnow (Pimephales promelas) and yellow lampmussel (Lampsilis cariosa).
AB  - Diffusive gradients in thin films (DGT) were assessed for their predictive
      capability of fathead minnow and yellow lampmussel bioaccumulation in copper (Cu)
      and lead (Pb) mixed metal exposures. Nine treatments with a matrix of 3 Cu and 3
      Pb concentrations were utilized. Exposures were coupled, with organisms and DGT
      exposed in tanks for 6 days. The Cu measured in fish, mussel, and DGT was found
      not to be influenced by Pb treatment, whereas Pb accumulation was impacted by the
      interaction of Cu and Pb treatment. The Pb accumulation increased with increasing
      Cu concentration, which was attributed to the different speciation of Cu and Pb
      in the water where Cu binds preferentially to ligands, decreasing its
      bioavailability and concomitantly displacing Pb from complexing sites. The DGT
      values were significantly correlated with accumulated Cu and Pb in the fish, but
      not with Pb in the mussel. In addition, DGT was determined to better predict
      aquatic organism bioaccumulation of Cu than the inorganic Cu fraction calculated
      by the speciation model, because DGT accumulated not only inorganic metal
      fractions but also complexes of metal and organic matter. The present study
      provides insights into metal speciation in polluted environments, extends the
      understanding of using DGT as a tool for estimating metal bioavailability, and
      provides implications for the selection of geochemical modeling, biological
      sampling, and passive sampling techniques for monitoring trace metal
      contamination. Environ Toxicol Chem 2018;9999:1-10. (c) 2018 SETAC.

PMID- 30284319
TI  - Clinical efficacy of the graft free slit-window sinus floor elevation procedure:
      A 2-year randomized controlled clinical trial.
AB  - OBJECTIVE: Slit-window technique is a lateral approach sinus floor elevation
      (SFE) procedure that utilizes a rigid resorbable membrane in conjunction with
      stabilizing bony slits to tent the Schneiderian membrane without addition of
      grafting materials. The aim of this randomized clinical trial was to compare
      clinical and radiographic outcomes of the Slit-window SFE with those of SFE with
      bone grafting. MATERIAL AND METHODS: Thirty-three patients with 38 edentulous
      sites were included. Edentulous sites were randomly allocated to the Slit-window
      SFE or SFE with bone grafting. Simultaneous with SFE, each site received two
      dental implants. Implant stability quotient (ISQ) values were recorded at
      baseline and monthly visits for 8 months. The bone coverage and bone height gain
      at implant sites were recorded on cone beam computed tomography (CBCT) scans 6
      and 24 months postoperatively. RESULTS: There were no significant differences in
      the mean ISQ values between the groups at any time point (p > 0.05). All implants
      in both groups were found to have complete bone coverage. Significant increases
      in the bone height were found 6 and 24 months postoperatively in both groups (p <
      0.001). CONCLUSIONS: Within limitations of the present study, it can be concluded
      that the Slit-window SFE technique without the need for bone grafting resulted in
      sufficient bone height gain around implants placed simultaneous with the SFE
      procedures. The bone height around these implants was stable during the 2-year
      follow-up period. The treatment outcomes for these implants were comparable to
      those placed simultaneous with lateral approach SFE in conjunction with bone
      grafting.

PMID- 30284320
TI  - Sediment and Biota Trace Element Distribution in Streams Disturbed by Upland
      Industrial Activity.
AB  - Extensive industrial areas in headwater stream watersheds can severely impact the
      physical condition of streams and introduce contaminants. We compared 3 streams
      that received stormwater runoff and industrial effluents from industrial
      complexes to two reference streams. Reference streams provide a benchmark of
      comparison of geomorphic form and stability in coastal plain, sandy-bottomed
      streams as well as concentrations of trace elements in sediment and biota in the
      absence of industrial disturbance. We used crayfish (Cambarus latimanus,
      Procambarus raneyi, P. acutus) and crane fly larvae (Tipula) as biomonitors of 15
      trace elements entering aquatic food webs. Streams with industrial areas were
      more scoured, deeply incised, and less stable. Sediment organic matter content
      broadly correlated to trace element accumulation, but fine sediments and organic
      matter were scoured from stream bottoms of disturbed streams. Trace element
      concentrations were higher in depositional zones than runs within all streams.
      Despite contaminant sources in the headwaters, trace element concentrations were
      generally not elevated in sediments of the eroded streams. However, element
      concentrations were frequently elevated in biota from these streams with
      taxonomic differences in accumulation amplified. In eroded, sand-bottomed coastal
      plain streams with unstable sediments, single snapshots of sediment trace element
      concentrations did not characterize well bioavailable trace elements. Biota that
      integrated exposures over time and space within their home ranges better detected
      bioavailable contaminants than sediment. This article is protected by copyright.
      All rights reserved.

PMID- 30284321
TI  - Achieving Thermo-Mechano-Opto-Responsive Bitemporal Colorful Luminescence via
      Multiplexing of Dual Lanthanides in Piezoelectric Particles and its
      Multidimensional Anticounterfeiting.
AB  - Optical characteristics of luminescent materials, including emission color
      (wavelength), lifetime, and excitation mode, play crucial roles in data
      communication and information security. Conventional luminescent materials
      generally display unicolor, unitemporal, and unimodal (occasionally bimodal)
      emission, resulting in low-level readout and decoding. The development of
      multicolor, multitemporal, and multimodal luminescence in a single material has
      long been considered to be a significant challenge. In this study, for the first
      time, the superior integration of colorful (red-orange-yellow-green), bitemporal
      (fluorescent and delayed), and four-modal (thermo-/mechano-motivated and
      upconverted/downshifted) emissions in a particular piezoelectric particle via
      optical multiplexing of dual-lanthanide dopants is demonstrated. The as-prepared
      versatile NaNbO3 :Pr3+ ,Er3+ luminescent microparticles shown are particularly
      suitable for embedding into polymer films to achieve waterproof,
      flexible/wearable and highly stretchable features, and synchronously to provide
      multidimensional codes that can be visually read-out using simple and commonly
      available tools (including the LED of a smartphone, pen writing, cooling-heating
      stimuli, and ultraviolet/near-infrared lamps). These findings offer unique
      insight for designing highly integrated stimuli-responsive luminophors and smart
      devices toward a wide variety of applications, particularly advanced
      anticounterfeiting technology.

PMID- 30284322
TI  - Biotransport of metallic trace elements from marine to terrestrial ecosystems by
      seabirds.
AB  - Physical systems, such as currents and winds, have traditionally been considered
      responsible for transporting contaminants. Although evidence is mounting that
      animals play a role in this process through their movements, we still know little
      about how such contaminant biotransport occurs and the extent of effects at
      deposition sites. In the present study, we address this question by studying how
      rhinoceros auklets (Cerorhinca monocerata), a seabird that occurs in immense
      colonies (~300 000 pairs at our study site, Teuri Island), affect contaminant
      levels at their colony and at nearby sites. More specifically, we hypothesize
      that contaminants are transported and deposited by seabirds at their colony and
      that these contaminants are passed on locally to the terrestrial ecosystem. To
      test this hypothesis, we analyzed the concentration of 9 heavy metal and
      metalloids, as well as delta13 C and delta15 N stable isotopes, in bird tissues,
      plants, and soil, both within and outside of the colony. The results show that
      rhinoceros auklets transport marine-derived mercury (Hg), possibly from their
      wintering location, and deposit Hg via their feces at their breeding site,
      thereby contaminating plants and soils within the breeding colony. The present
      study confirms not only that animals can transport contaminants from marine to
      terrestrial ecosystems, potentially over unexpectedly long distances, but also
      that bird tissues contribute locally to plant contamination. Environ Toxicol Chem
      2018;9999:1-9. (c) 2018 SETAC.

PMID- 30284323
TI  - Self-controlled case series studies: Just how rare does a rare non-recurrent
      outcome need to be?
AB  - The self-controlled case series method assumes that adverse outcomes arise
      according to a non-homogeneous Poisson process. This implies that it is
      applicable to independent recurrent outcomes. However, the self-controlled case
      series method may also be applied to unique, non-recurrent outcomes or first
      outcomes only, in the limit where these become rare. We investigate this rare
      outcome assumption when the self-controlled case series method is applied to non
      recurrent outcomes. We study this requirement analytically and by simulation, and
      quantify what is meant by 'rare' in this context. In simulations we also apply
      the self-controlled risk interval design, a special case of the self-controlled
      case series design. To illustrate, we extract data on the incidence rate of some
      recurrent and non-recurrent outcomes within a defined study population to check
      whether outcomes are sufficiently rare for the rare outcome assumption to hold
      when applying the self-controlled case series method to first or unique outcomes.
      The main findings are that the relative bias should be no more than 5% when the
      cumulative incidence over total time observed is less than 0.1 per individual.
      Inclusion of age (or calendar time) effects will further reduce bias. Designs
      that begin observation with exposure maximise bias, whereas little or no bias
      will be apparent when there is no time trend in the distribution of exposures, or
      when exposure is central within time observed.

PMID- 30284325
TI  - Congenital malformations are associated with secondhand smoke among nonsmoking
      women: A meta-analysis.
AB  - BACKGROUND: The association between active maternal smoking and congenital
      malformations is well established, but little is known about the association
      between secondhand smoke and congenital malformations. Moreover, studies
      regarding the association between congenital malformations and secondhand smoke
      have not yielded consistent results. METHODS: In July 2018, we searched PubMed,
      EMBASE, and China Biology Medicine databases for observational studies
      characterizing the relationship between secondhand smoke and congenital
      malformations of offspring in nonsmoking women. Two reviewers independently
      decided on whether a study should be included, did data extraction, and assessed
      study quality. Pooled risks with 95% confidence intervals were calculated using
      either the fixed-effects models or random-effects models. Further subgroup
      analyses and sensitivity analyses were performed to explore the potential source
      of heterogeneity and to examine the robustness of risk estimates. RESULTS: Thirty
      three studies with a total of 31 944 cases and 32 335 controls were included.
      Secondhand smoke exposure was associated with an increased risk of congenital
      malformations (odds ratio = 1.92; 95% confidence interval 1.61-2.30). Secondhand
      smoke was correlated with significantly increased risk for digestive system (1.17
      [1.05-1.32]), nervous system (1.74 [1.33-2.29]), and cardiovascular system (2.10
      [1.32-3.35]) malformations and for oral clefts (1.87 [1.47-2.39]). CONCLUSIONS:
      Secondhand smoke exposure increases the risk for overall and several organ-system
      malformations. These findings highlight the necessity of improving community
      awareness to prevent secondhand smoke exposure during the preconception and
      conception periods.

PMID- 30284324
TI  - The myodural bridge in the common rock pigeon (Columbia livia): Morphology and
      possible physiological implications.
AB  - The dense connective tissue that connects muscles to the cervical spinal dura
      mater is known as the myodural bridge in human anatomy and has been a subject of
      interest to anatomists and clinicians. The myodural bridge was originally
      discovered in humans, and also has been observed in other mammals and in
      reptilian sauropsids. We investigated the existence of the myodural bridge in a
      bird, that is, the Common Rock Pigeon Columba livia, to expand the understanding
      of the structure and function of the myodural bridge. Gross anatomical dissection
      of seven specimens and histological analyses of the suboccipital region of eight
      specimens were performed. The rectus capitis dorsalis minor muscle joins
      occipital periosteal extensions and inserts with several dense connective tissue
      cords on the dorsal side of the dura mater of the cervical spinal cord. The
      myodural bridge consists primarily of collagen Type I fibres, suggesting that the
      myodural bridge can transmit strong tensional forces generated by the contraction
      of M. rectus capitis dorsalis minor to the dura mater. The pull on the dura mater
      may affect the circulation of the cerebrospinal fluid in the subarachnoid space
      of the spine.

PMID- 30284326
TI  - Sonographic appearances of adrenal schwannomas.
AB  - OBJECTIVE: To evaluate the sonographic ultrasound (US) appearances of adrenal
      gland schwannomas. MATERIALS AND METHODS: This was a retrospective analysis of 15
      cases of schwannomas involving the adrenal gland. The following US features were
      assessed: size, border, echogenicity, homogeneity, intralesional cystic necrosis,
      presence of septa, intralesional calcification, posterior acoustic enhancement
      and blood supply. RESULTS: Of the 15 tumors, seven (46.7%) were located on the
      left side, and the remaining eight (53.3%) on the right side. The most frequent
      US appearance of adrenal schwannoma was a single, well-defined and isoechoic
      mass. The internal echotexture was homogeneous in 2 cases, and heterogeneous in
      13 cases, with intralesional cystic areas (n = 11), septa (n = 10) or
      calcifications (n = 6). Posterior acoustic enhancement was seen in 12 of the 15
      cases (80%). On color Doppler US, 86.7% (13/15) of the lesions did not show any
      vascularity. CONCLUSIONS: Adrenal schwannomas usually present on US as well
      defined isoechoic masses often with posterior acoustic enhancement, cystic
      necrosis with septa and poor blood supply. These appearances should suggest the
      diagnosis of adrenal schwannomas. Nevertheless, additional information from
      laboratory tests and CT or MR imaging may be required to avoid unnecessary
      surgery.

PMID- 30284328
TI  - Effects of Vitamin D levels and supplementation on atopic dermatitis: A
      systematic review.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin condition
      affecting 5%-20% of children worldwide. Studies suggested both a correlation
      between serum vitamin D (VD) levels and AD severity and a therapeutic potential
      role for VD supplementation. OBJECTIVES: To determine whether serum VD levels
      correlate with AD severity and the effects of supplementation for disease
      improvement in children. DATA SOURCES: Ovid MEDLINE, EMBASE, and Cochrane Library
      databases were searched. STUDY SELECTION: Publications with children 0-18 years
      old with AD and data evaluating effects of VD levels or supplementation on AD
      severity were included. DATA EXTRACTION: Author, year, inclusion criteria, study
      design, location, age, VD levels, VD supplementation regimens, and baseline and
      final disease severities were extracted. RESULTS: Of the 21 included
      publications, 15, 5, and 1 evaluated VD level, VD supplementation, and both
      factors with disease severity, respectively. There were 4 randomized control
      trials (RCTs), 5 cohort, 6 case-control, and 6 cross-sectional studies. A
      significant inverse correlation between VD level and severity was described in
      62.5% (10/16) of studies. There were 67% (4/6) that reported a significant
      improvement in AD severity with supplementation. LIMITATIONS: Studies meeting
      inclusion criteria were limited. Furthermore, papers were heterogeneous in terms
      of location, season, and VD supplementation regimen. Language and publication
      bias was another potential limitation. CONCLUSION: In children, the majority of
      existing literature confirmed a link between serum VD levels and AD severity.
      Weak evidence was found supporting improvement of AD with VD supplementation.
      Future large-scale studies are needed to support our findings.

PMID- 30284329
TI  - A Scalable, High-Throughput, and Environmentally Benign Approach to Polymer
      Dielectrics Exhibiting Significantly Improved Capacitive Performance at High
      Temperatures.
AB  - High-temperature capability is critical for polymer dielectrics in the next
      generation capacitors demanded in harsh-environment electronics and electrical
      power applications. It is well recognized that the energy-storage capabilities of
      dielectrics are degraded drastically with increasing temperature due to the
      exponential increase of conduction loss. Here, a general and scalable method to
      enable significant improvement of the high-temperature capacitive performance of
      the current polymer dielectrics is reported. The high-temperature capacitive
      properties in terms of discharged energy density and the charge-discharge
      efficiency of the polymer films coated with SiO2 via plasma-enhanced chemical
      vapor deposition significantly outperform the neat polymers and rival or surpass
      the state-of-the-art high-temperature polymer nanocomposites that are prepared by
      tedious and low-throughput methods. Moreover, the surface modification of the
      dielectric films is carried out in conjunction with fast-throughput roll-to-roll
      processing under ambient conditions. The entire fabrication process neither
      involves any toxic chemicals nor generates any hazardous by-products. The
      integration of excellent performance, versatility, high productivity, low cost,
      and environmental friendliness in the present method offers an unprecedented
      opportunity for the development of scalable high-temperature polymer dielectrics.

PMID- 30284330
TI  - An Effective Dark-Vis-UV Ternary Biomimetic Switching Based on N3/Spiropyran
      Modified Nanochannels.
AB  - Many natural photomodulated nanochannels are investigated and are crucial for
      biological activity. Biomimetic nanochannels with a bistable conductance state
      under light stimulus are demonstrated. In this system, two molecules, cis-bis
      (4,4'-dicarboxy-2,2'-bipyridine) dithiocyanato ruthenium(II) (N3) and spiropyran
      1'-(3-carboxypropyl)-3',3'-dimethyl-6-nitro-spiro[2H-1]benzopyran-2,2'-indoline
      (SP-COOH), each with unique photoresponsive properties, are modified in alumina
      nanochannels. The two segments of the hourglass-shaped alumina nanochannels are
      designated to graft a certain molecule. Under ultraviolet (UV) or visible light
      (vis) irradiation, electrons belonging to N3 are excited, resulting in negatively
      charged surfaces on the sides of nanochannels modified with N3 molecules. Only
      under UV stimulus, the conformation change of the SP-COOH molecules leads to
      positively charged surfaces of nanochannels in the SP-COOH occupied sides.
      Benefiting from the joint effect of N3 and SP-COOH, low, medium, and high (i.e.,
      "0," "1," and "2") ternary levels of ion conductance are established under the
      dark-vis-UV alternate stimuli. The multistage current switching containing "0-1-2
      0" and "0-1-2-1-0" procedures is stable and robust. Additionally, the diode-like
      ion transport behavior of the nanochannels could be exploited to support a
      multivalued logical gating with the management of light signals.

PMID- 30284331
TI  - Three-dimensional spin-echo-based black-blood MRA in the detection of vasospasm
      following subarachnoid hemorrhage.
AB  - BACKGROUND: Black-blood MR angiography (BBMRA), which utilizes a non-T1 contrast
      spin-echo type technique, has been expected to overcome several issues associated
      with time-of-flight (TOF) MRA. PURPOSE: To investigate the efficacy of BBMRA to
      detect vasospasms following subarachnoid hemorrhage (SAH). STUDY TYPE:
      Retrospective. SUBJECTS: Seventeen patients with SAH in their early posttreatment
      period. FIELD STRENGTH/SEQUENCE: BBMRA, which uses a volumetric isotropic turbo
      spin-echo acquisition (VISTA), and TOF-MRA on 1.5T scanners. ASSESSMENT:
      Visualization of supratentorial arteries and veins in BBMRA was rated on a 4
      point scale by two neuroradiologists. Another neuroradiologist independently
      assessed TOF-MRA. The degree of the vasospasm was then evaluated using a 3-point
      scale by the same readers. The diagnostic performance of the MRAs was evaluated
      using computed tomography angiography (CTA) or digital subtraction angiography
      (DSA) as the standard of reference. STATISTICAL TESTS: Wilcoxon signed rank test,
      McNemar test, and Cohen's kappa coefficient. RESULTS: BBMRA provided superior
      visualization of the anterior and middle cerebral arteries than TOF-MRA (P <
      0.05). The depiction of the veins was more pronounced on BBMRA (P < 0.01). Of the
      166 arterial segments evaluated by CTA or DSA, 23 (13.9%) could not be assessed
      using TOF-MRA because of high signal hemorrhage, whereas BBMRA enabled
      visualization of all the segments. Vasospasm was confirmed in 30 segments by CTA
      or DSA. The sensitivity, specificity, and positive and negative predictive values
      were 73, 96, 76, and 95 for TOF-MRA and 91, 100, 100, and 98 for BBMRA,
      respectively (P = 0.13 for sensitivity, P = 0.06 for specificity). The agreement
      of the degree of vasospasm between MRA and the standard of reference, as
      indicated by kappa value, was 0.71 (95% confidence interval [CI], 0.55-0.87) for
      TOF-MRA and 0.91 (95% CI, 0.82-0.99) for BBMRA. DATA CONCLUSION: BBMRA, owing to
      its contrast properties, may be superior to TOF-MRA for the evaluation of
      intracranial arteries after SAH. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage
      2.

PMID- 30284332
TI  - Modulating long-range energetics via helix stabilization: A case study using T4
      lysozyme.
AB  - Cooperative protein folding requires distant regions of a protein to interact and
      provide mutual stabilization. The mechanism of this long-distance coupling
      remains poorly understood. Here, we use T4 lysozyme (T4L*) as a model to
      investigate long-range communications across two subdomains of a globular
      protein. T4L* is composed of two structurally distinct subdomains, although it
      behaves in a two-state manner at equilibrium. The subdomains of T4L* are
      connected via two topological connections: the N-terminal helix that is
      structurally part of the C-terminal subdomain (the A-helix) and a long helix that
      spans both subdomains (the C-helix). To understand the role that the C-helix
      plays in cooperative folding, we analyzed a circularly permuted version of T4L*
      (CP13*), whose subdomains are connected only by the C-helix. We demonstrate that
      when isolated as individual fragments, both subdomains of CP13* can fold
      autonomously into marginally stable conformations. The energetics of the N
      terminal subdomain depend on the formation of a salt bridge known to be important
      for stability in the full-length protein. We show that the energetic contribution
      of the salt bridge to the stability of the N-terminal fragment increases when the
      C-helix is stabilized, such as occurs upon folding of the C-terminal subdomain.
      These results suggest a model where long-range energetic coupling is mediated by
      helix stabilization and not specific tertiary interactions.

PMID- 30284333
TI  - The nature and timing of distress among post-treatment haematological cancer
      survivors.
AB  - Many people with haematological cancers will not meet the diagnostic criteria for
      a psychological disorder, but will still suffer distress during treatment and
      beyond. The current study aimed to explore the nature and timing of psychosocial
      distress experienced by haematological cancer survivors. Twenty-three post
      treatment haematological cancer survivors participated in a semi-structured
      interview. Data were analysed using thematic analysis which involved identifying,
      analysing and reporting themes. Four themes were identified: Apprehension about
      leaving the safety of the health care system comprises the struggles encountered
      when transitioning from patient to survivor, Uncertainty and life transitions in
      the post-treatment period encompasses the changes survivors face when attempting
      to re-enter their "normal" lives, Distress associated with ongoing physical
      problems or impairment describes issues associated with the ongoing physical
      sequelae, and Fear of recurrence encapsulates how the continuing threat of cancer
      recurrence impacted survivors. This study has found that distress is ongoing for
      many haematological cancer survivors in the post-treatment period. It is
      imperative that distress is identified and support offered to those in need to
      prevent further psychosocial issues. It is especially important to consider the
      psychosocial needs of survivors in the post-treatment stage who are discharged
      from the health system may be unsure where to seek help.

PMID- 30284335
TI  - Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2.
AB  - Peroxiredoxins are thiol-dependent peroxidases that function in peroxide
      detoxification and H2 O2 induced signaling. Among the six isoforms expressed in
      humans, PRDX1 and PRDX2 share 97% sequence similarity, 77% sequence identity
      including the active site, subcellular localization (cytosolic) but they hold
      different biological functions albeit associated with their peroxidase activity.
      Using recombinant human PRDX1 and PRDX2, the kinetics of oxidation and
      hyperoxidation with H2 O2 and peroxynitrite were followed by intrinsic
      fluorescence. At pH 7.4, the peroxidatic cysteine of both isoforms reacts nearly
      tenfold faster with H2 O2 than with peroxynitrite, and both reactions are orders
      of magnitude faster than with most protein thiols. For both isoforms, the
      sulfenic acids formed are in turn oxidized by H2 O2 with rate constants of ca 2 *
      103 M-1 s-1 and by peroxynitrous acid significantly faster. As previously
      observed, a crucial difference between PRDX1 and PRDX2 is on the resolution step
      of the catalytic cycle, the rate of disulfide formation (11 s-1 for PRDX1, 0.2 s
      1 for PRDX2, independent of the oxidant) which correlates with their different
      sensitivity to hyperoxidation. This kinetic pause opens different pathways on
      redox signaling for these isoforms. The longer lifetime of PRDX2 sulfenic acid
      allows it to react with other protein thiols to translate the signal via an
      intermediate mixed disulfide (involving its peroxidatic cysteine), whereas PRDX1
      continues the cycle forming disulfide involving its resolving cysteine to
      function as a redox relay. In addition, the presence of C83 on PRDX1 imparts a
      difference on peroxidase activity upon peroxynitrite exposure that needs further
      study.

PMID- 30284334
TI  - Poly(ionic liquid)-Derived N-Doped Carbons with Hierarchical Porosity for Lithium
      and Sodium-Ion Batteries.
AB  - The performance of lithium- and sodium-ion batteries relies notably on the
      accessibility to carbon electrodes of controllable porous structure and chemical
      composition. This work reports a facile synthesis of well-defined N-doped porous
      carbons (NPCs) using a poly(ionic liquid) (PIL) as precursor, and graphene oxide
      (GO)-stabilized poly(methyl methacrylate) (PMMA) nanoparticles as sacrificial
      template. The GO-stabilized PMMA nanoparticles are first prepared and then
      decorated by a thin PIL coating before carbonization. The resulting NPCs reach a
      satisfactory specific surface area of up to 561 m2 g-1 and a hierarchically meso-
      and macroporous structure while keeping a nitrogen content of 2.6 wt%. Such NPCs
      deliver a high reversible charge/discharge capacity of 1013 mA h g-1 over 200
      cycles at 0.4 A g-1 for lithium-ion batteries, and show a good capacity of 204 mA
      h g-1 over 100 cycles at 0.1 A g-1 for sodium-ion batteries.

PMID- 30284336
TI  - Validation of the Spanish version of the Cancer Symptom Scale in Hispanic cancer
      patients.
AB  - AIM: To assess the validity of the translated Spanish Cancer Symptom Scale.
      BACKGROUND: Instruments to facilitate comprehensive and objective assessments of
      the cancer symptom experience in underrepresented populations are essential.
      METHODS: The Cancer Symptom Scale was translated into Spanish, and a back
      translation was conducted. During June 2016, a sample of 121 Hispanic Puerto
      Rican patients with any cancer diagnosis, all undergoing cancer treatments,
      completed four paper surveys. A subgroup of 15 patients agreed to complete the
      Spanish Cancer Symptom Scale a second time after a short delay of 1 to 2 hours.
      Construct validity and reliability (internal consistency via Cronbach alpha and
      test-retest reliability) was evaluated. RESULTS: All the Intensity Items of the
      Spanish Cancer Symptom Scale correlated significantly with the matched items on
      the MD Anderson Symptom Inventory. In a subgroup of 77 participants, each Cancer
      Symptom Scale subscale total of scores correlated significantly with the total
      scores from the Functional Assessment of Cancer Therapy-General. Discriminant
      validity was demonstrated between those receiving chemotherapy and those from
      post treatment. The Spanish Cancer Symptom Scale internal consistency reliability
      was 0.98. CONCLUSION: The Spanish Cancer Symptom Scale has excellent evidence of
      validity and reliability for assessing cancer-therapy-related symptoms.

PMID- 30284337
TI  - Throughput efficiency and service quality after process redesign at a cancer day
      care unit: Two sides of the coin?
AB  - This study was designed to focus on the patient perspective in a reorganisation
      of care processes at a cancer day care unit (CDU). The effects of dose banding
      and of taking blood samples one day (or more) before the day care treatment (on
      Day -1) are investigated in terms of throughput efficiency and perceived service
      quality. Data were collected by mapping patient processes in detail and surveying
      patients in two CDUs at a university hospital (n = 308). A univariate model was
      used to investigate the effect of these factors on patient throughput time, and
      perceived service quality was examined with multiple linear regression. Taking
      blood samples on Day -1 decreases patient throughput time and increases the
      perceived service quality by improving the patient's perception of technical
      expertise and the outcome. This has a globally positive effect on patients'
      perceived service quality. Dose banding affected neither patient throughput time
      nor perceived service quality. Taking the pretreatment blood sample on Day -1 can
      be considered an important process design characteristic, as it increases both
      efficiency and service quality.

PMID- 30284338
TI  - Percutaneous Peripheral Nerve Stimulation (PNS) for the Treatment of Chronic Low
      Back Pain Provides Sustained Relief.
AB  - OBJECTIVES: The objective of this study was to evaluate the use of percutaneous
      peripheral nerve stimulation (PNS) for the treatment of chronic low back pain
      (LBP). Percutaneous PNS offers the potential to provide an effective
      neuromodulation therapy using a system and fine-wire leads designed specifically
      for percutaneous use with history of an excellent safety profile. MATERIALS AND
      METHODS: Subjects with chronic axial LBP received percutaneous PNS leads
      targeting the medial branch of the dorsal ramus in the region of LBP. Lead
      placement was guided using ultrasound and confirmed by selective activation of
      the lumbar multifidus and patient-reported sensations. The percutaneous fine-wire
      leads remained in place for the 30-day therapy. RESULTS: A majority of subjects
      reported statistically and clinically significant reductions in both average pain
      intensity (BPI-5) and worst pain intensity (BPI-3) scores with PNS treatment,
      which continued long term at the four-month follow-up visit. Subject-reported
      reductions in pain intensity were substantiated by concomitant and sustained
      reductions in analgesic medication usage. Subjects also reported clinically
      significant reductions in patient-centric outcomes of disability (Oswestry
      Disability Index), pain interference (BPI-9), and patient global impression of
      change (PGIC). CONCLUSIONS: This work demonstrates the potential value of
      percutaneous PNS for the treatment of chronic LBP. Improvements in pain,
      medication, and patient-centric outcomes, which were sustained long term after
      the removal of PNS leads, demonstrate the significance of this innovative
      approach to treat chronic LBP.

PMID- 30284340
TI  - Chronic stress and intestinal permeability: Lubiprostone regulates glucocorticoid
      receptor-mediated changes in colon epithelial tight junction proteins, barrier
      function, and visceral pain in the rodent and human.
AB  - BACKGROUND: Chronic psychological stress is associated with increased intestinal
      epithelial permeability and visceral hyperalgesia. Lubiprostone, an agonist for
      chloride channel-2, promotes secretion and accelerates restoration of injury
      induced epithelial barrier dysfunction. The mechanisms underlying how
      lubiprostone regulates colon epithelial barrier function and visceral
      hyperalgesia in chronic stress remain unknown. METHODS: Male rats were subjected
      to water avoidance stress for 10 consecutive days. Lubiprostone was administered
      daily during the stress phase. Visceromotor response to colorectal distension was
      measured. Human colon crypts and cell lines were treated with cortisol and
      lubiprostone. The transepithelial electrical resistance and FITC-dextran
      permeability were assayed. Chromatin immunoprecipitation was conducted to assess
      glucocorticoid receptor binding at tight junction gene promoters. KEY RESULTS:
      Lubiprostone significantly decreased chronic stress-induced visceral hyperalgesia
      in the rat (P < 0.05; n = 6). WA stress decreased occludin and claudin-1 and
      increased claudin-2 in rat colon crypts, which was prevented by lubiprostone.
      Cortisol treatment induced similar alterations of tight junction protein
      expression in Caco-2/BBE cells (P < 0.05) and significantly changed paracellular
      permeability in monolayers (P < 0.01). These changes were blocked by
      lubiprostone. Glucocorticoid receptor and its binding at occludin promoter region
      were decreased in cortisol-treated cells and human colon crypts, which was
      largely reversed by lubiprostone. In rat colonic cells, glucocorticoid receptor
      and its co-chaperone proteins were down-regulated after corticosterone treatment
      and lubiprostone reversed these changes. CONCLUSIONS & INFERENCES: Lubiprostone
      preferentially prevents chronic stress-induced alterations of intestinal
      epithelial tight junctions, barrier function, and visceral hyperalgesia that was
      associated with modulation of glucocorticoid receptor expression and function.

PMID- 30284339
TI  - Novel cinnamic acid-tryptamine hybrids as potent butyrylcholinesterase
      inhibitors: Synthesis, biological evaluation, and docking study.
AB  - A novel series of cinnamic acid-tryptamine hybrids was designed, synthesized, and
      evaluated as cholinesterase inhibitors. Anticholinesterase assays showed that all
      of the synthesized compounds displayed a clearly selective inhibition of
      butyrylcholinesterase (BChE), but only a moderate inhibitory effect toward
      acetylcholinesterase (AChE) was detected. Among these cinnamic acid-tryptamine
      hybrids, compound 7d was found to be the most potent inhibitor of BChE with an
      IC50 value of 0.55 +/- 0.04 MUM. This compound showed a 14-fold higher inhibitory
      potency than the standard drug donepezil (IC50  = 7.79 +/- 0.81 MUM) and
      inhibited BChE through a mixed-type inhibition mode. Moreover, a docking study
      revealed that compound 7d binds to both the catalytic anionic site (CAS) and the
      peripheral anionic site (PAS) of BChE. Also, compound 7d was evaluated against
      beta-secretase, which exhibited low activity (inhibition percentage: 38%).

PMID- 30284341
TI  - Integration of an N-Heterocyclic Carbene Precursor into a Covalent Triazine
      Framework for Organocatalysis.
AB  - The successful incorporation of a thermally fragile imidazolium moiety into a
      covalent triazine framework resulted in a heterogeneous organocatalyst active in
      carbene-catalyzed umpolung reaction. The structural integrity of the imidazolium
      moiety was confirmed by combining solid-state NMR and XPS experiments.

PMID- 30284342
TI  - Copulatory mechanism and functional morphology of genitalia and anal horn of the
      scorpionfly Cerapanorpa dubia (Mecoptera: Panorpidae).
AB  - The scorpionfly genus Cerapanorpa is characterized by the male possessing a
      single finger-like anal horn on the posterior portion of tergite VI. However, the
      functional morphology of this anal horn and the genitalia have not been studied
      to date. Herein, we investigated the functional morphology of the genitalia and
      the nongenital structures of the scorpionfly Cerapanorpa dubia by observing the
      mating process and dissecting the freeze-fixated pairs in copula to reveal the
      copulatory mechanism. The male C. dubia provides a solid salivary mass to the
      female as a nuptial gift prior to copulation. When the female starts to feed on
      the gift, the male uses his notal organ and complex genital structures to control
      the closest wing and genitalia of the female to establish a V-shaped mating
      position. In the maintenance phase of copulation, the male uses his anal horn in
      cooperation with the basally-constricted abdominal segment VII to clamp female
      abdominal segment VIII. The male hypovalves grasp female cerci, and move up and
      down rhythmically. The paired parameres clasp both sides of female tergite IX.
      The basal processes on male gonostyli grip the pleural membranes of the female
      genital chamber. In the sperm transfer phase, the male aedeagus directly couples
      with the female medigynium to transmit sperm by connecting his phallotreme to the
      female's copulatory pore. The evolution of the male complex grasping structures
      in Panorpidae is also briefly discussed.

PMID- 30284344
TI  - Tuning the Phase Transition from UCST-Type to LCST-Type by Composition Variation
      of Polymethacrylamide Polymers.
AB  - Polymethacrylamide copolymers with hydrophobic N-substituted acrylamides, such as
      N-cyclohexylacrylamide and N-tert-butylacrylamide, are rare examples of polymers
      showing composition-dependent thermoresponsive behavior in water. They show
      unexpected behavior different from the conventional copolymers of a
      thermoresponsive polymer with hydrophobic comonomers. On increasing the amount of
      the hydrophobic comonomer in the polymer, there is a change from UCST-type phase
      behavior to complete solubility, followed by compositions showing LCST-type
      transition and insolubility in water (U-S-L-I-type change). At 50 mol% of less
      hydrophobic N-tert-butyl acrylamide (logP 0.87) in contrast to ~25 mol% of N
      cyclohexylacrylamide (logP 1.51), the broad UCST-type transition of
      polymethacrylamide is turned to LCST-type transitions with very narrow hysteresis
      in water and PBS buffer. The use of H-bond and water-structure breaker showed the
      role of H-bonding and hydrophobic interactions in phase transitions of UCST-type
      and LCST-type, respectively. This work is an important add-on to the infant field
      of nonionic polymers of UCST-type.

PMID- 30284343
TI  - Improving the delivery of physical activity services in lung cancer: A
      qualitative representation of the patient's perspective.
AB  - OBJECTIVE: To explore patient experiences of, and preferences for, physical
      activity after a lung cancer diagnosis. METHODS: This was a qualitative study
      involving seven patients who had been treated for lung cancer within the previous
      2 years. Participants attended a focus group interview. Conventional content
      analysis methodology was used to analyse the text by two independent researchers.
      RESULTS: Eight major themes emerged from the data. These were as follows: the
      influence of past lifestyle and chronic disease; the perceived benefits of
      physical activity; using physical activity to facilitate return to activities of
      daily living; the impact of symptoms, capacity and motivation; family and peer
      support; access to services; health professionals; and enjoyment of different
      types of physical activity. Patients suggested several factors that could improve
      their healthcare experience. These include access to exercise professionals
      particularly after cancer treatment; access to information about physical
      activity in different formats; supervision from health professionals and peer
      support; and use of behaviour change strategies to achieve sustainable increases
      in physical activity. CONCLUSION: Our results should be considered in the
      improvement of lung cancer care pathways as we strive to implement physical
      activity services into routine clinical care.

PMID- 30284345
TI  - Array-based profiling of the lymphoma cell DNA methylome does not unequivocally
      distinguish primary lymphomas of the central nervous system from non-CNS diffuse
      large B-cell lymphomas.
AB  - Primary lymphomas of the central nervous system (PCNSL) are diffuse large B-cell
      lymphomas (DLBCLs) confined to the central nervous system (CNS). We here
      performed array-based DNA methylation analyses of 26 PCNSL and 78 DLBCL and
      validated our findings in an independent dataset. We identified 2847 CpGs
      differentially methylated between PCNSL and non-CNS-DLBCL. Neither a supervised
      analysis using these CpGs nor application of 3 CpG classifiers selected for class
      separation unambiguously separated PCNSL from non-CNS-DLBCL. Remarkably, 6/78 non
      CNS-DLBCL consistently segregated with PCNSL, which displayed molecular features
      typical for PCNSL. Our findings suggest that a subset of non-CNS-DLBCL exists
      which molecularly resembles PCNSL.

PMID- 30284346
TI  - A Medically Challenging Case of Chronic Pelvic Pain and the Use of Burst
      Suppression Spinal Cord Stimulator as a Treatment Modality.

PMID- 30284347
TI  - Effect of Microscopic Susceptibility Gradients on Chemical-Shift-Based Fat
      Fraction Quantification in Supraclavicular Fat.
AB  - BACKGROUND: Susceptibility differences between fat and water can cause changes in
      the water-fat frequency separation that can negatively affect the accuracy of fat
      fraction techniques. This may be especially relevant for brown adipose tissue, as
      MRI fat fraction techniques have been proposed for its detection. PURPOSE: To
      assess the effect of microscopic magnetic susceptibility gradients on the water
      fat frequency separation and its impact on chemical-shift-based fat fraction
      quantification techniques in the supraclavicular fat, where brown adipose tissue
      is commonly found in humans. STUDY TYPE: Prospective.
      POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: Subjects: 11 healthy
      volunteers, mean age of 26 and mean BMI of 23, three overweight volunteers, mean
      age of 38 and mean BMI of 33. Phantoms: bovine phantom and intralipid fat
      emulsion. Simulations: various water-fat distributions. FIELD STRENGTH/SEQUENCE:
      Six-echo gradient echo chemical-shift-encoded sequence at 3T. ASSESSMENT: Fat
      fraction values as obtained from a water-fat spectral model accounting for
      susceptibility-induced water-fat frequency variations were directly compared to
      traditional spectral models that assume constant water-fat frequency separation.
      STATISTICAL TESTS: Two-tail t-tests were used for significance testing (p <
      0.05.) A Bayesian Information Criterion difference of 6 between fits was taken as
      strong evidence of an improved model. RESULTS: Phantom experiments and simulation
      results showed variations of the water-fat frequency separation up to 0.4 ppm and
      0.6 ppm, respectively. In the supraclavicular area, the water-fat frequency
      separation produced by magnetic susceptibility gradients varied by as much as +/
      0.4 ppm, with a mean of 0.08 +/- 0.14 ppm, producing a mean difference in fat
      fraction of -1.26 +/- 5.26%. DATA CONCLUSION: In the supraclavicular fat depot,
      microscopic susceptibility gradients that exist within a voxel between water and
      fat compartments can produce variations in the water-fat frequency separation.
      These variations may produce fat fraction quantification errors of 5% when a
      spectral model with a fixed water-fat frequency separation is applied, which
      could impact MR brown fat techniques. LEVEL OF EVIDENCE: 1 Technical Efficacy:
      Stage 1 J. Magn. Reson. Imaging 2018.

PMID- 30284348
TI  - Ethnic variations in the childhood prevalence of Hirschsprung disease in New
      Zealand.
AB  - BACKGROUND: Epidemiological studies have suggested that there may be ethnic
      variations in the prevalence of Hirschsprung disease (HD) but no study has
      systematically investigated this issue or potential ethnic variations in the
      extent of aganglionosis in HD. This study aimed to investigate this in a
      childhood population in New Zealand. METHODS: A multicentre national
      retrospective review was undertaken of all newly diagnosed cases of HD at each of
      the four paediatric surgical centres in New Zealand over a 16-year period
      (January 2000 to December 2015). Original histological, radiological and
      operative reports were obtained and analysed. Self-identified ethnicity was
      recorded from admission documents. Birth statistics were obtained from Statistics
      New Zealand. RESULTS: A total of 246 cases of HD were identified. The prevalence
      of HD was 1:3790 live births for European, 1:6610 among Maori, 1:1834 among
      Pacific Peoples, 1:3847 among Asian and 1:5694 among Middle Eastern. The
      prevalence of HD was statistically significantly greater in Pacific Peoples (P <
      0.0005). The proportion of children with long-segment HD was also significantly
      greater in Pacific and Asian populations than others (P = 0.04). These findings
      were not due to differences in the proportion of familial cases of HD among the
      different populations. CONCLUSIONS: The prevalence and phenotype of HD varies
      significantly between different ethnic groups within New Zealand. This may well
      be related to variations in the frequencies of HD-associated gene mutations
      within these populations.

PMID- 30284350
TI  - Safety, Feasibility, and Efficacy of Transcutaneous Tibial Nerve Stimulation in
      Acute Spinal Cord Injury Neurogenic Bladder: A Randomized Control Pilot Trial.
AB  - OBJECTIVES: We investigated whether transcutaneous tibial nerve stimulation
      (TTNS) in acute spinal cord injury was safe and feasible, and could achieve
      neuromodulation and improve cystometrogram parameters during acute inpatient
      rehabilitation. MATERIALS AND METHODS: Participants were consecutive acute
      traumatic spinal cord injury patients admitted for acute inpatient
      rehabilitation, randomized to a 2-week trial of TTNS v sham stimulation. Primary
      outcomes were safety and feasibility of TTNS and secondary outcomes were bladder
      measures based on pre- and post-TTNS cystometrogram by group and within groups,
      including bladder capacity, detrusor hyperreflexia, pressures, and detrusor
      sphincter dyssynergia, as well as filling sensations and desire to void. The
      principle investigator and subjects were blinded to treatment allocation.
      RESULTS: A total of 19 subjects consented to the study and completed the
      stimulation protocol. Morbidity was similar between groups and compliance was
      100% to the TTNS protocol. Based on a lack of rehabilitation interruptions and
      comments from staff, TTNS was feasible. Post-cystometrogram parameters were
      significant for lower volumes until sensation in the control group and prolonged
      volumes until sensation in the TTNS group. The control group had significant
      changes of increased detrusor-sphincter dyssynergia and decreased bladder
      capacity. This was not significantly changed in the TTNS group. CONCLUSIONS: TTNS
      is a safe and feasible modality that can be performed during inpatient
      rehabilitation of acute traumatic spinal cord injury. Bladder capacity and
      episodes of detrusor-sphincter dyssynergia significantly worsened in the control
      group and did not significantly change in the TTNS group, suggesting that TTNS
      can alter the course of neurogenic bladder via neuromodulation.

PMID- 30284349
TI  - Cardiovascular safety of oral semaglutide in patients with type 2 diabetes:
      Rationale, design and patient baseline characteristics for the PIONEER 6 trial.
AB  - AIMS: To assess the cardiovascular (CV) safety of oral semaglutide, the first
      tablet formulation of a glucagon-like peptide-1 receptor agonist. MATERIALS AND
      METHODS: PIONEER 6 is a multinational, randomized, placebo-controlled, double
      blind trial in patients with type 2 diabetes at high risk of CV events (defined
      as being aged >=50 years and having established CV disease [CVD] or moderate
      [stage 3] chronic kidney disease [CKD], or being aged >=60 years with >=1 other
      CV risk factor). Patients were randomized to once-daily oral semaglutide (up to
      14 mg) or placebo added to standard of care. The primary composite endpoint is
      time to first occurrence of CV death or non-fatal myocardial infarction or non
      fatal stroke. The primary hypothesis was to exclude an excess in CV risk with
      oral semaglutide by assessing non-inferiority versus placebo for the primary
      endpoint (non-inferiority margin of 1.8 for the upper boundary of the 95%
      confidence interval of the hazard ratio). PIONEER 6 is event-driven, with follow
      up continuing until accrual of at least 122 primary outcome events. There is no
      pre-defined minimal duration. RESULTS: Overall, 3183 patients have been enrolled
      (mean age 66.1 years, 31.6% females) in 214 sites across 21 countries. At
      baseline, the mean duration of diabetes was 14.9 years, mean glycated haemoglobin
      concentration was 66 mmol/mol (8.2%), and 84.6% of patients had established
      CVD/moderate CKD. CONCLUSIONS: PIONEER 6 will provide evidence regarding the CV
      safety of oral semaglutide in patients with type 2 diabetes and high CV risk.

PMID- 30284351
TI  - Efficacy of phototherapy in pityriasis lichenoides chronica of dark skin: A
      retrospective study from a tertiary center in Mexico.

PMID- 30284352
TI  - Effectiveness of high-intensity interval training combined with resistance
      training versus continuous moderate-intensity training combined with resistance
      training in patients with type 2 diabetes: A one-year randomized controlled
      trial.
AB  - AIMS: To evaluate the impact of one-year high intensity interval training (HIIT)
      combined with resistance training (RT) vs continuous moderate intensity training
      (MCT) combined with RT on glycaemic control, body composition and
      cardiorespiratory fitness (CRF) in patients with type 2 diabetes. MATERIALS AND
      METHODS: A randomized controlled trial included 96 participants with type 2
      diabetes for a one-year supervised exercise intervention with three groups:
      Control, HIIT with RT and MCT with RT). The control group received standard
      counseling regarding general PA guidelines, with no structured exercise sessions.
      The main outcome variable was HbA1c (%). Secondary outcomes were other glycaemic
      variables, body composition, anthropometry measurements, CRF and enjoyment of
      exercise. Generalized estimating equations (GEE) were used to model outcomes.
      RESULTS: Among the 96 participants enrolled in the intervention, 80 were
      randomized, with a mean (SD) age of 58.5 years (7.7) and a mean HbA1c of 7.2%
      (1.6). After adjusting the model for sex and total moderate-to-vigorous physical
      activity (MVPA), we found that both the MCT with RT (beta, 0.003; P, 0.921) and
      the HIIT with RT (beta, 0.025; P, 0.385) groups had no effect on HbA1c. A
      favourable effect was observed in the MCT with RT group, with a reduction in
      whole body fat index (beta, -0.062; P, 0.022), android fat index (beta, -0.010;
      P, 0.010) and gynoid fat index (beta, -0.013; P, 0.014). Additionally, CRF
      increased during the intervention, but only in the MCT with RT group (beta,
      0.185; P, 0.019). CONCLUSIONS: The results from this study suggest that there was
      no effect of either MCT with RT or HIIT with RT on glycaemic control in
      individuals with type 2 diabetes. However, the combination of MCT and RT improved
      body composition and CRF following a one-year intervention.

PMID- 30284353
TI  - Thai version of the Functional Rating Index for patients with back and neck pain:
      Part II responsiveness and head-to-head comparisons.
AB  - OBJECTIVES: To examine responsiveness and estimate minimal clinically important
      difference (MCID) of the Thai version of Functional Rating Index (Thai FRI) and
      examine head-to-head comparisons of the Thai FRI and other questionnaires.
      METHODS: This study related to validation of a questionnaire and head-to-head
      comparisons. Patients with low back pain (LBP) completed the Thai FRI, Roland
      Morris (RM), modified Oswestry, and multilevel RM disability questionnaires.
      Patients with neck pain (NP) completed the Thai FRI and Neck Disability Index at
      the first visit and 2-week follow-up. Patients and therapists rated Global
      Perceived Effect Scales (GPES). Effect size (ES), standardized response mean
      (SRM), correlations between the GPES with changes in questionnaire scores, and
      area under receiver operating characteristic curve (AUC) were calculated. The
      MCID was also estimated. RESULTS: Eighty-four patients with LBP and 52 patients
      with NP completed the Thai FRI. ES = 1.34 for LBP; 1.28 for NP, SRM = 1.32 for
      LBP; 1.20 for NP, correlation = 0.49 for LBP; 0.38 for NP, AUC = 0.83 for both
      groups. MCID = 11.5 for LBP; 12.5 FRI points for NP. CONCLUSION: The Thai FRI
      demonstrated responsiveness with large ES. Its MCID ranged from 11.5 to 12.5 FRI
      points. The Thai FRI had comparable responsiveness to other questionnaires and
      was appropriate for use in the patients with back and/or neck pain.

PMID- 30284354
TI  - The use of rituximab in treatment of epidermolysis bullosa acquisita: Three new
      cases and a review of the literature.
AB  - Epidermolysis bullosa acquisita (EBA) is a rare, subepidermal blistering disease
      affecting the skin and mucous membranes that often remains refractory to standard
      immunosuppressive therapy. We present three original cases and a review of the
      literature of 20 cases of refractory EBA treated with rituximab as monotherapy or
      in combination with other agents. Complete control (with or without therapy) and
      remission were seen in 56% of patients treated with rituximab monotherapy and 75%
      of patients treated with rituximab and immunoadsorption (IA). We conclude EBA
      refractory to standard immunosuppressive therapy may show a more favorable long
      term response to the addition of rituximab; and rituximab in combination with
      intravenous immunoglobulin or IA may provide utility in terminating acute
      disease. Additional data are needed to evaluate the safety and long-term outcomes
      of rituximab-based treatment.

PMID- 30284355
TI  - Prevalence of toxoplasmosis and its association with dementia in older adults in
      Central Africa: a result from the EPIDEMCA programme.
AB  - OBJECTIVE: We aimed at estimating the seroprevalence of Toxoplasma gondii (T.
      gondii) infection in older adults living in Central Africa and investigating its
      association with dementia using data from the Epidemiology of Dementia in Central
      Africa (EPIDEMCA) programme. METHODS: A cross-sectional multicentre population
      based study was carried out among participants aged 73 (+/-7) years on average,
      living in rural and urban areas of the Central African Republic and the Republic
      of Congo between November 2011 and December 2012. Blood samples were collected
      from each consenting participant. The detection of anti-T. gondii immunoglobulin
      G antibodies was performed in 2014 in France using a commercially available ELISA
      kit. Participants were interviewed using a standardised questionnaire including
      sociodemographic characteristics. DSM-IV criteria were required for a diagnosis
      of dementia. Multivariate binary logistic regression models were used to assess
      the association between toxoplasmosis infection and dementia. RESULTS: Among 1662
      participants, the seroprevalence of toxoplasmosis was 63.0% (95% confidence
      interval (CI): 60.7-65.3) overall, 66.6% (95%CI: 63.4-69.8) in Central African
      Republic and 59.4% (95%CI: 56.1-62.7) in the Republic of Congo. In multivariate
      analyses, toxoplasmosis status was significantly associated with increasing age
      (P = 0.006), Republic of Congo (P = 0.002), urban area (P = 0.001) and previous
      occupation (P = 0.002). No associations between dementia and toxoplasmosis status
      or anti-T. gondii IgG titres were found. CONCLUSION: Toxoplasma gondii infection
      was not associated with dementia among older adults in Central Africa. Our
      findings are consistent with previous studies and add to the knowledge on the
      relationship between T. gondii infection and neurological disorders.

PMID- 30284356
TI  - Anterior, frontal congenital triangular alopecia, redundancy in therapy without
      improvement.
AB  - Congenital triangular alopecia (CTA) is a benign noncicatricial localized pattern
      of hair loss with unknown etiology. Although referred to as "congenital," CTA may
      develop in adulthood. It is believed that many cases of CTA are never diagnosed
      or are misdiagnosed; causing the incidence to be underestimated. The present
      study evaluates a case of 20-year-old woman presenting with a single circular to
      oval area of hair-loss in the mid-frontal region of her scalp. To date, about 170
      cases of CTA have been reported and we present the first case in which the
      alopecic patch is located in the mid-frontal region of the scalp. We present this
      case not only to challenge the preconceived notion that all CTAs are
      frontotemporal, but also to inform other practitioners about this rare condition
      and prevent redundant medical treatment.

PMID- 30284357
TI  - Isomerism of the Aniline Trimer.
AB  - Weaker intermolecular forces expand the isomerization alternatives for molecular
      aggregation, as observed for the prototype models of the aniline trimer (An3 )
      and the monohydrated aniline dimer (An2 -W) when compared to the phenol trimer.
      In this experiment the aniline clusters were generated in a jet-cooled expansion
      and probed using broadband (chirped-pulsed) microwave spectroscopy. Three isomers
      of the aniline trimer and two isomers of the hydrated dimer were detected and
      characterized in the rotational spectrum. In the homotrimer the weak N-H???N
      hydrogen bonds are assisted by subtle combinations of N-H???pi and C-H???pi
      interactions, producing several competing low-lying ring species in the gas
      phase. One of the aniline trimers is a symmetric top, topologically equivalent to
      the only observed phenol trimer. Conversely, addition of a water molecule to the
      aniline dimer introduces a leading O-H???N interaction, making water to behave as
      dominant hydrogen-bond pivot between the two aniline molecules. This combination
      of weak intermolecular interactions critically tests the performance of
      dispersion-corrected or parametrized density-functional methods. Evaluation of
      the B3LYP-D3(BJ) and M06-2X methods revealed deficiencies of the Truhlar
      functional to reproduce the experimental rotational data.

PMID- 30284359
TI  - Composition Tailoring via N and S Co-doping and Structure Tuning by Constructing
      Hierarchical Pores: Metal-Free Catalysts for High-Performance Electrochemical
      Reduction of CO2.
AB  - A facile route to scalable production of N and S co-doped, hierarchically porous
      carbon nanofiber (NSHCF) membranes (ca. 400 cm2 membrane in a single process) is
      reported. As-synthesized NSHCF membranes are flexible and free-standing, allowing
      their direct use as cathodes for efficient electrochemical CO2 reduction reaction
      (CO2 RR). Notably, CO with 94 % Faradaic efficiency and -103 mA cm-2 current
      density are readily achieved with only about 1.2 mg catalyst loading, which are
      among the best results ever obtained by metal-free CO2 RR catalysts. On the basis
      of control experiments and DFT calculations, such outstanding CO Faradaic
      efficiency can be attributed to the co-doped pyridinic N and carbon-bonded S
      atoms, which effectively decrease the Gibbs free energy of key *COOH
      intermediate. Furthermore, hierarchically porous structures of NSHCF membranes
      impart a much higher density of accessible active sites for CO2 RR, leading to
      the ultra-high current density.

PMID- 30284360
TI  - OC02: Second systolic peak in middle cerebral artery Doppler of fetuses with
      severe anemia: an explanatory model based on fetal pulse wave reflection.

PMID- 30284358
TI  - Magnetic Resonance Elastography in the Assessment of Acute Effects of Kinesio
      Taping on Lumbar Paraspinal Muscles.
AB  - BACKGROUND: Kinesio tape (KT) is an elastic therapeutic tape used for treating
      sports-related injuries and a number of other disorders. To date, the objective
      evidence to link pathophysiological effects and actual reactions triggered by KT
      is limited. PURPOSE: To explore the effect of KT on the lumbar paraspinal muscles
      by magnetic resonance (MR) elastography. STUDY TYPE: Prospective observational
      study. POPULATION: Sixty-six asymptomatic volunteers with 31 women and 35 men.
      FIELD STRENGTH/SEQUENCE: 3.0T MRI and elastography with vibration frequency of
      120 Hz. ASSESSMENT: The 5-cm-width KT with full tension was placed on a single
      side of the lumbar paraspinal muscle. The taping side and adhering direction were
      randomly decided. Two rectangular regions of interest (ROIs) of 5- and 2.5-cm
      width were positioned at the bilateral paraspinal regions from the L2 to L4 level
      on the confidence map of MR elastography before and after KT taping. The mean
      shear stiffness values of the ROIs at the superficial, middle, and deep depths
      were recorded; then the differences between the taping and reference sides were
      calculated. STATISTICAL TESTS: Paired t-test and Pearson correlations were used
      to evaluate the stiffness changes after KT application and intraoperator errors
      of the stiffness measures on the reference side, respectively. RESULTS: A
      significant decrease in the muscle stiffness value between taping and reference
      sides (-0.71 kPa +/- 0.60 with KT and -0.25 kPa +/- 0.78 without KT, P < 0.0001
      for 5-cm ROI; -0.67 kPa +/- 1.12 with KT and -0.16 kPa +/- 1.17 without KT, P =
      0.0004 for 2.5-cm ROI) was found in the superficial depth, but no significant
      differences in the middle and deep depths (P = 0.25 and P = 0.79 for 5-cm ROI; P
      = 0.09 and P = 0.67 for 2.5-cm ROI, respectively). There were no significant
      differences of muscle stiffness differences between gender (P = 0.11 for
      superficial, P = 0.37 for middle, P = 0.78 for deep) and taping direction (P =
      0.18 for superficial, P = 0.13 for middle, P = 0.15 for deep). DATA CONCLUSION:
      Our results demonstrate that KT can reduce the MR elastography-derived shear
      stiffness in the superficial depth of paraspinal muscles. LEVEL OF EVIDENCE: 2
      Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 30284361
TI  - OC01: Transvaginal ultrasonography compared with magnetic resonance imaging for
      the diagnosis of adenomyosis.

PMID- 30284362
TI  - OC05: Ultrasound and hematological early-luteal-phase predictors of severe
      ovarian hyperstimulation syndrome in high-risk patients following triggering of
      final oocyte maturation with human chorionic gonadotropin.

PMID- 30284363
TI  - OC04: Alterations in mid-trimester amniotic fluid levels of resistin, leptin and
      tumor necrosis factor-a in pregnancies with trisomy 18 or 13 and euploid embryos.

PMID- 30284364
TI  - Reply.

PMID- 30284365
TI  - OC03: Use of IOTA guidelines in Rwanda to determine the presence of ovarian
      cancer in patients with adnexal masses.

PMID- 30284366
TI  - Re: Effectiveness of 12-13-week scan for early diagnosis of fetal congenital
      anomalies in the cell-free DNA era.

PMID- 30284367
TI  - Editor's Note.

PMID- 30284368
TI  - Quality of life: fractionated stereotactic radiotherapy versus enucleation
      treatment in uveal melanoma patients.
AB  - PURPOSE: To report the quality of life and visual functioning in uveal melanoma
      patients treated with enucleation or fractionated stereotactic radiation therapy
      (fSRT). METHODS: Uveal melanoma (UM) patients treated with fSRT (n = 65) or
      enucleation (n = 48) participated in this prospective study. Questionnaires to
      measure anxiety (State-Trait Anxiety Inventory), subjective distress (Impact of
      Event Scale) and quality of life (EORTC-QLQ-C30 and National Eye Institute Visual
      Function Questionnaire (VFQ-25)) were obtained before treatment and 2, 6, 12, 24,
      36 and 48 months after treatment. RESULTS: Less peripheral vision was observed
      until 3 years (p = 0.026) posttreatment in enucleated patients compared to
      irradiated patients. From 2 months until 3 years posttreatment irradiated
      patients increase in role functioning-score (p = 0.005), while enucleated
      patients decrease in score (p = 0.012). Regardless of their treatment, for all
      patients we measured a reduction in physical functioning (p = 0.035), insomnia (p
      < 0.001) and in state anxiety from pretreatment until 2 years posttreatment (p <
      0.001). An increase in pain overall (p = 0.023) and in emotional functioning is
      observed 1 year posttreatment (p < 0.001). At baseline, patients with metastases
      (independent of their treatment) have more subjective distress (p = 0.037) than
      patients without metastases. The mean 'global health score' overall, without
      effect of time, was 76.4 (SD: 13.6). CONCLUSION: Enucleated patients had more
      difficulty working or performing household tasks 2 months posttreatment compared
      to irradiated patients. Enucleated patients had diminished peripheral vision
      until 3 years compared to irradiated patients. Overall quality of life is not
      significantly different between both treatment groups.

PMID- 30284370
TI  - Evaluation of offline adaptive planning techniques in image-guided brachytherapy
      of cervical cancer.
AB  - Modern three-dimensional image-guided intracavitary high dose rate (HDR)
      brachytherapy is often used in combination with external beam radiotherapy (EBRT)
      to manage cervical cancer. Intrafraction motion of critical organs relative to
      the HDR applicator in the time between the planning CT and treatment delivery can
      cause marked deviations between the planned and delivered doses. This study
      examines offline adaptive planning techniques that may reduce intrafraction
      uncertainties by shortening the time between the planning CT and treatment
      delivery. Eight patients who received EBRT followed by HDR boosts were
      retrospectively reviewed. A CT scan was obtained for each insertion. Four
      strategies were simulated: (A) plans based on the current treatment day CT; (B)
      plans based on the first fraction CT; (C) plans based on the CT from the
      immediately preceding fraction; (D) plans based on the closest anatomically
      matched previous CT, using all prior plans as a library. Strategies B, C, and D
      allow plans to be created prior to the treatment day insertion, and then rapidly
      compared with the new CT. Equivalent doses in 2 Gy for combined EBRT and HDR were
      compared with online adaptive plans (strategy A) at D90 and D98 for the high-risk
      CTV (HR-CTV), and D2 cc for the bladder, rectum, sigmoid, and bowel. Compared to
      strategy A, D90 deviations for the HR-CTV were -0.5 +/- 2.8 Gy, -0.9 +/- 1.0 Gy,
      and -0.7 +/- 1.0 Gy for Strategies B, C, and D, respectively. D2 cc changes for
      rectum were 2.7 +/- 5.6 Gy, 0.6 +/- 1.7 Gy, and 1.1 +/- 2.4 Gy for Strategies B,
      C, and D. With the exception of one patient using strategy B, no notable
      variations for bladder, sigmoid, and bowel were found. Offline adaptive planning
      techniques can shorten time between CT and treatment delivery from hours to
      minutes, with minimal loss of dosimetric accuracy, greatly reducing the chance of
      intrafraction motion.

PMID- 30284371
TI  - The Longitudinal Danish High Myopia Study, Cohort 1948: at age 66 years visual
      ability is only occasionally affected by visual field defects.
AB  - PURPOSE: A descriptive study on visual fields, as part of a 50-year follow-up of
      high myopia in an unselected cohort-based Danish sample, now aged 66 years.
      METHODS: In a Copenhagen 1948 birth cohort (n = 9243), 39 individuals aged 14
      years were identified with myopia of at least -6 D, and with regular clinical
      follow-ups since then. In 2002 (n = 34, age 54 years) and 2008 (n = 32, age 60),
      the individual ambulatory visual field was outlined by kinetic Goldmann large
      object perimetry (IV or V,4e). At age 66 years, 28 attended for the 2014-2015
      follow-up, at which smaller Goldmann objects (II and I,4e) were added, further to
      identify relative defects. RESULTS: Repeated large object perimetry disclosed
      statistically significant general peripheral narrowing over the 12-13-year test
      period, though slight and without practical implications. Two new cases showing
      absolute defects were however added to the three already known. The addition of
      small Goldmann objects disclosed relative defects in another eight participants,
      in some to suggest a refraction-related pattern (fundus ectasia; uncorrected high
      myopia). However, comparing eyes with and without defects, statistical importance
      could not be attached to the degree of myopia, fundus ectasia or optic disc
      morphology (chi2 , n.s.). CONCLUSION: (i) Serial large object Goldmann isopters
      over the 'senior' decade up to age 66 demonstrated a slight general peripheral
      narrowing by age of visual fields in high myopia. (ii) Overall 42% of the
      participants had absolute or relative defects (in 5 and 8, respectively),
      however, without socio-visual consequences when binocular. (iii) Visual field
      loss by age still appears a minor issue in clinically unselected high myopia.

PMID- 30284372
TI  - Laser Direct Writing of Heteroatom (N and S)-Doped Graphene from a
      Polybenzimidazole Ink Donor on Polyethylene Terephthalate Polymer and Glass
      Substrates.
AB  - In this paper, for the first time, a laser direct writing technique is reported
      to form S- and N-doped graphene patterns on thin (0.3 mm thickness) polyethylene
      terephthalate (PET) and glass substrates from a specially formulated organic
      polybenzimidazole (PBI) ink, without thermally affecting the substrates and
      without the need for a metallic precursor. Unlike standard graphene ink printing,
      postcuring at high temperatures is not needed here, thus avoiding potential
      substrate distortion and damages. A UV laser beam of 355 nm wavelength is used to
      generate photochemical reactions to break the C?S bond (2.8 eV) from dimethyl
      sulfoxide (DMSO, a component of the PBI ink) and the C?N bond (3.14 eV) of PBI
      and form N- and S-doped graphene on the substrates. The sheet resistance of the
      laser-induced graphene is as low as 12 Omega sq-1 on PET, matching that of indium
      tin oxide (ITO). The laser-written doped graphene shows hydrophilic
      characteristics, unlike pristine graphene. The S- and N-doped graphene allows the
      tailoring of bandgaps and thus controlling electrical and chemical properties.
      The optical transparency of the written graphene is below 10% which could be
      improved in the future. Potential applications include printing of flexible
      circuits and sensors, and smart wearables.

PMID- 30284373
TI  - Metabolic Management Center: An innovation project for the management of
      metabolic diseases and complications in China.

PMID- 30284374
TI  - Laboratory monitoring of P2Y12 inhibitors: communication from the SSC of the
      ISTH.

PMID- 30284375
TI  - Northward expansion of the bivoltine life cycle of the cricket over the last four
      decades.
AB  - Recent climate warming has affected some life-history traits of insects,
      including voltinism and body size. The magnitude of changes in these traits may
      differ latitudinally within a species because of the differing lengths of season
      available for growth. The present study aims to estimate the change in voltinism
      of the lawn ground cricket, Polionemobius mikado (Shiraki) (Orthoptera:
      Trigonidiidae), over the last four decades by comparing the body size between
      adults collected from a wide range of latitudes in Japan in recent years (2015
      2017) and those collected four decades ago (1969-1976). The body size of adults
      collected in recent years showed a latitudinal saw-tooth cline, in the same way
      as body size did four decades ago, and the cline shifted northward over the last
      four decades: In 2015-2017, the body size decreased slightly with increasing
      latitude from 31 degrees N to 36 degrees N, and then increased to 40 degrees N,
      and again decreased from 40 degrees N to 44 degrees N. Comparison of the body
      size between recent years and four decades ago revealed that the body size has
      decreased significantly at the middle latitudes (36-40 degrees N), suggesting
      that the proportion of smaller bivoltine individuals there has increased over the
      last four decades. The sum of effective temperatures for postdiapause embryonic
      development at around 36 degrees N in recent years was comparable to that at 31
      35 degrees N four decades ago, at which P. mikado populations were bivoltine.
      Taken together, these findings suggested that the latitudinal range suitable for
      the bivoltine life cycle of P. mikado has expanded northward over the last four
      decades because of climate warming. This is the first report that shows that a
      decrease in body size can be caused by climate warming via an increase in
      voltinism.

PMID- 30284376
TI  - Automated quantification of reference levels in liver and mediastinal blood pool
      for the Deauville therapy response classification using FDG-PET/CT in Hodgkin and
      non-Hodgkin lymphomas.
AB  - BACKGROUND: 18F-FDG-PET/CT has become a standard for assessing treatment response
      in patients with lymphoma. A subjective interpretation of the scan based on the
      Deauville 5-point scale has been widely adopted. However, inter-observer
      variability due to the subjectivity of the interpretation is a limitation. Our
      main goal is to develop an objective and automated method for evaluating
      response. The first step is to develop and validate an artificial intelligence
      (AI)-based method, for the automated quantification of reference levels in the
      liver and mediastinal blood pool in patients with lymphoma. METHODS: The AI-based
      method was trained to segment the liver and the mediastinal blood pool in CT
      images from 80 lymphoma patients, who had undergone 18F-FDG-PET/CT, and apply
      this to a validation group of six lymphoma patients. CT segmentations were
      transferred to the PET images to obtain automatic standardized uptake values
      (SUV). The AI-based analysis was compared to corresponding manual segmentations
      performed by two radiologists. RESULTS: The mean difference for the comparison
      between the AI-based liver SUV quantifications and those of the two radiologists
      in the validation group was 0.02 and 0.02, respectively, and 0.02 and 0.02 for
      mediastinal blood pool respectively. CONCLUSIONS: An AI-based method for the
      automated quantification of reference levels in the liver and mediastinal blood
      pool shows good agreement with results obtained by experienced radiologists who
      had manually segmented the CT images. This is a first, promising step towards
      objective treatment response evaluation in patients with lymphoma based on 18F
      FDG-PET/CT.

PMID- 30284377
TI  - Decision-making for cataract surgery: Changes within 7 years.

PMID- 30284378
TI  - Use of a commercial ion chamber detector array for the measurement of high
      spatial-resolution photon beam profiles.
AB  - Linear accelerator (linac) commissioning and quality assurance measurements are
      time-consuming tasks that often require a water tank scanning system to acquire
      profile scans for full characterization of dosimetric beam properties. To
      increase efficiency, a method is demonstrated to acquire variable resolution,
      photon beam profile data using a commercially available ion chamber array (0.5 cm
      detector spacing). Field sizes of 2 * 2, 5 * 5, 10 * 10, and 15 * 15 cm2 were
      acquired at depths in solid water of dmax , 5 cm, and 10 cm; additionally, beam
      profiles for field sizes of 25 * 25 and 40 * 40 cm2 were acquired at 5 cm depth
      in solid water at x-ray energies of 6 and 23 MV. 1D composite profiles were
      generated by combining discrete point measurements made at multiple couch
      positions. The 1D composite profile dataset was evaluated against a commissioning
      dataset acquired with a 3D water tank scan system utilizing (a) 0.125 cc ion
      chamber for 5 * 5, 10 * 10, 15 * 15, 25 * 25, and 40 * 40 field sizes and (b) a
      solid state detector for 2 * 2 cm2 field size. The two datasets were compared to
      the gamma criteria at 1%/1 mm and 2%/2 mm tolerance. Almost all pass rates
      exceeded 95% at 2%/2 mm except for the 6 MV 2 * 2 cm2 field size at dmax . Pass
      rates at 1%/1 mm ranged from 51% to 99%, with an average pass rate of 82%. A
      fourfold reduction in MU was achieved for scans larger than 15 * 15 cm2 using
      this method compared to the water tank scans. Further, dynamic wedge measurements
      acquired with the ion chamber array showed reasonable agreement with the
      treatment planning system. This method opens up new possibilities for rapid
      acquisition of variable resolution 2D-3D dosimetric data mitigating the need for
      acquiring all scan data with in-water measurements.

PMID- 30284379
TI  - Correlation of peripapillary retinal nerve fibre layer thickness with visual
      acuity in paediatric patients affected by optic pathway glioma.
AB  - PURPOSE: To evaluate peripapillary retinal nerve fibre layer (RNFL) thickness,
      measured by spectral-domain optical coherence tomography (SD-OCT), as a surrogate
      of visual function in a population of paediatric patients affected by optic
      pathway glioma (OPG) associated with neurofibromatosis type 1 (NF1). METHODS: A
      total of 38 paediatric patients (66 eyes) affected by MRI-proven OPG were
      included. Each patient underwent complete ophthalmological examination, including
      age-appropriate visual acuity (VA) assessment and RNFL analysis by SD-OCT. Visual
      acuity was classified as normal or pathologic using age-based normative data.
      Visual acuity was correlated to mean RNFL thickness of the whole peripapillary
      area and of each single analyzed sector (nasal, superior, temporal, inferior).
      RESULTS: Visual acuity was normal in 43 (65%) and pathologic in 23 (35%) eyes.
      Mean parapapillary RNFL thickness of each analyzed sector was significantly lower
      in eyes with abnormal VA (p < 0.05). The best balanced cut-off value of global
      RNFL thickness allowing to discriminate between eyes with normal and pathologic
      VA was 76.25 MUm (91%, 76%, 67% and 94% of sensitivity, specificity, positive and
      negative predicting value, respectively). Considering best balanced cut-off
      values of other analyzed RNFL sectors, the superior (p = 0.0029) and the inferior
      (p = 0.0024) sectors reached the higher sensitivity (87% and 87%, respectively)
      and specificity (81% and 79%, respectively). CONCLUSION: Retinal nerve fibre
      layer thickness is directly related to VA in children affected by NF1-related
      OPG, and should be considered as a potential surrogate marker of VA. Retinal
      nerve fibre layer thickness cut-off values can be used in paediatric patients to
      discriminate false-positive results obtained by VA measurement.

PMID- 30284381
TI  - Personalized risk-based screening for diabetic retinopathy: A multivariate
      approach versus the use of stratification rules.
AB  - AIMS: To evaluate our proposed multivariate approach to identify patients who
      will develop sight-threatening diabetic retinopathy (STDR) within a 1-year screen
      interval, and explore the impact of simple stratification rules on prediction.
      MATERIALS AND METHODS: A 7-year dataset (2009-2016) from people with diabetes
      (PWD) was analysed using a novel multivariate longitudinal discriminant approach.
      Level of diabetic retinopathy, assessed from routine digital screening
      photographs of both eyes, was jointly modelled using clinical data collected over
      time. Simple stratification rules based on retinopathy level were also applied
      and compared with the multivariate discriminant approach. RESULTS: Data from 13
      103 PWD (49 520 screening episodes) were analysed. The multivariate approach
      accurately predicted whether patients developed STDR or not within 1 year from
      the time of prediction in 84.0% of patients (95% confidence interval [CI] 80.4
      89.7), compared with 56.7% (95% CI 55.5-58.0) and 79.7% (95% CI 78.8-80.6)
      achieved by the two stratification rules. While the stratification rules detected
      up to 95.2% (95% CI 92.2-97.6) of the STDR cases (sensitivity) only 55.6% (95% CI
      54.5-56.7) of patients who did not develop STDR were correctly identified
      (specificity), compared with 85.4% (95% CI 80.4-89.7%) and 84.0% (95% CI 80.7
      87.6%), respectively, achieved by the multivariate risk model. CONCLUSIONS:
      Accurate prediction of progression to STDR in PWD can be achieved using a
      multivariate risk model whilst also maintaining desirable specificity. While
      simple stratification rules can achieve good levels of sensitivity, the present
      study indicates that their lower specificity (high false-positive rate) would
      therefore necessitate a greater frequency of eye examinations.

PMID- 30284380
TI  - Peritumoural adipose tissue pro-inflammatory cytokines are associated with
      tumoural growth factors in cancer cachexia patients.
AB  - BACKGROUND: Cancer cachexia (CC) is a multifactorial syndrome, often
      irreversible, that affects patients with cancer influenced, in part, by the
      inflammatory condition. Peritumoural adipose tissue produces adipokines and
      angiogenic, apoptotic, and growth factors; given the possible crosstalk between
      the peritumoural adipose tissue and tumour, these may play an important role in
      cancer biology and carcinogenesis. METHODS: The aim of this study was to evaluate
      the factors produced by peritumoural adipose tissue in a cohort of 16 colorectal
      cancer patients with either weight-stable cancer (WSC; n = 7) or CC (n = 9). The
      study was approved by the Ethics Research Committee (972.914). Samples of
      peritumoural adipose tissue were analysed for concentrations of TNF-alpha, IL
      1beta, STAT-1, STAT-3, RANTES, IL-1Ra, IP-10, IL-15, MCP-1, IFN-alpha, GCSF,
      FADD, and TGF-beta. The cytokines and proteins were measured using Multiplex.
      Correlations between the proteins and cytokines were evaluated. RESULTS: TNF
      alpha, STAT-1, and FADD, a factor involved in apoptosis, were significantly
      higher in CC group than in the WSC group. In the peritumoural adipose tissue of
      the CC group, RANTES showed a significant positive correlation with IL-1Ra and IP
      10 and a negative correlation with IFN-alpha; and GCSF showed significant
      negative correlations with IL-1Ra, IP-10, IL-15, and MCP-1 and a positive
      correlation with IFN-alpha. In the peritumoural adipose tissue of the WSC group,
      no significant correlations were detected between RANTES, GCSF, IL-3, FADD, and
      STAT-1 and the cytokines/chemokines analysed. CONCLUSIONS: These results
      indicated that inflammatory and tumorigenic pathways were altered in peritumoural
      adipose tissue in CC. Furthermore, inflammatory cytokines were correlated with
      growth factors in the peritumoural adipose tissue of cachectic patients,
      suggesting that inflammatory cytokines modulated the proliferative environment
      closely linked to the tumour.

PMID- 30284382
TI  - Health 2.0 2018.
AB  - Martin J. Kurian, Peter J. Rentzepis, Ann M. Carracher, and Kelly L. Close are of
      Close Concerns (http://www.closeconcerns.com), a healthcare information company
      focused exclusively on diabetes and obesity care. Close Concerns publishes Closer
      Look, a periodical that brings together news and insights in these areas. Each
      month, the Journal of Diabetes includes this News feature, in which Kurian,
      Rentzepis, Carracher, and Close review the latest developments relevant to
      researchers and clinicians.

PMID- 30284383
TI  - Superior outcome of corneal collagen cross-linking using riboflavin with
      methylcellulose than riboflavin with dextran as the main supplement.
AB  - PURPOSE: To compare the effect of corneal collagen cross-linking (CXL) on
      progressive keratoconus using 0.1% riboflavin with either dextran or
      methylcellulose as the main supplement. METHODS: In a comparative case series,
      CXL was performed in 40 patients (40 eyes) using a riboflavin solution containing
      either dextran (dextran-riboflavin; n = 20) or methylcellulose (methylcellulose
      riboflavin; n = 20). Changes in central corneal thickness (CCT), Scheimpflug
      tomography, maximal keratometry reading (Kmax ), visual acuity (VA) and
      endothelial cell density (ECD) were recorded. Stromal changes one month after
      surgery were analysed using optical coherence tomography (OCT) and in vivo
      confocal microscopy (IVCM). RESULTS: The CCT was significantly higher in the
      methylcellulose-riboflavin group during the CXL procedure. The IVCM demarcation
      line depth was 274 +/- 80 (SD) MUm in the dextran-riboflavin group and 442 +/- 80
      MUm in the methylcellulose-riboflavin group (p < 0.001). Complete absence of
      keratocytes in the pre-endothelial stroma was found in none of the corneas
      treated with dextran-riboflavin and in 42% of the corneas treated with
      methylcellulose-riboflavin. Visibility of the OCT demarcation line was
      significantly lower in the methylcellulose-riboflavin group. Kmax and corrected
      distance visual acuity were improved in the methylcellulose-riboflavin group and
      stable in the dextran-riboflavin group after 2 years. Endothelial cell density
      (ECD) was stable in both groups. CONCLUSION: We found deeper structural changes
      in the methylcellulose-riboflavin group than in the dextran-riboflavin group.
      This may be explained by different riboflavin solution properties and raises
      safety concerns. The study also indicates improved effect using methylcellulose
      riboflavin than dextran-riboflavin, possibly explained by deeper stromal CXL
      effect.

PMID- 30284384
TI  - Creation and Location-Specific Revision of a Core Nursing Outcomes Evaluation
      System Based on Nursing Outcomes Classification for Stroke Inpatients in China.
AB  - PURPOSE: To screen and create a core nursing outcomes evaluation index system
      based on NOC for stroke inpatients in China. METHODS: This study adopted the
      method of Delphi expert consultation, with the degree of consent >4.0 points and
      the coefficient of variation <0.25 as the standard for inclusion of indexes.
      RESULTS: The evaluation index system established in this study includes five
      first-grade indexes, 15 second-grade indexes, and 58 third-grade indexes.
      CONCLUSION: The evaluation index system of core nursing outcomes for stroke
      inpatients in China has good specificity and reliability. PRACTICE IMPLICATIONS:
      The evaluation index system of core nursing outcomes provides a standardized
      location-specific tool for clinical nurses to evaluate the nursing quality and
      intervention effect for stroke inpatients in China.

PMID- 30284385
TI  - Topical cyclosporine-A versus prednisolone for herpetic stromal keratitis: a
      randomized controlled trial.
AB  - PURPOSE: To compare topical cyclosporine-A 2% eye drop (Cs-A) with prednisolone
      acetate 1% eye drop for treatment of herpetic stromal keratitis (HSK). METHODS:
      In this randomized clinical trial, 38 eyes of 33 patients with HSK were randomly
      assigned to receive either 2% Cs-A or 1% prednisolone acetate eye drops. All
      subjects received oral acyclovir 400 mg twice a day. Slit-lamp examination,
      Scheimpflug tomography corneal optical densitometry (Pentacam(r), Oculus Inc.,
      Wetzlar, Germany), best-corrected visual acuity (BCVA), and intra-ocular pressure
      (IOP) were evaluated at the first visit, and 14 and 30 days after the treatment.
      RESULTS: Within-group analysis revealed significant improvement of total cornea
      optical density after 30 days of treatment in both groups (30.3 +/- 10.5 to 28.3
      +/- 9.8, p < 0.001 for prednisolone group, and 30.5 +/- 8.8 to 28.8 +/- 8.3 p <
      0.001 for Cs-A group, mean +/- SD). We were not able to disclose any significant
      difference between the two groups regarding the improvement of cornea optical
      density (p = 0.66). Best-corrected visual acuity (BCVA) logMAR significantly
      improved in both groups after 30 days of treatment (0.20 +/- 0.52, p = 0.002 in
      prednisolone group, and 0.24 +/- 0.31, p < 0.001 in Cs-A group, mean +/- SD).
      Analysis between groups did not show a significant difference of BCVA improvement
      (p = 0.45). We did not observe any severe side effect attributable to drugs.
      CONCLUSIONS: Cs-A 2% and prednisolone acetate 1% topical eye drops are effective
      for treatment of HSK.

PMID- 30284386
TI  - Otitis media, antibiotics, and risk of autism spectrum disorder.
AB  - Otitis media infections and antibiotic treatment have been linked to the risk of
      developing autism spectrum disorder. Broad-spectrum antibiotics may alter the
      composition of the gut flora microbiota, which is hypothesized to be involved in
      the regulation of the immune system. This study examines the interplay among
      otitis media, antibiotics, and the subsequent risk of developing autism. Based on
      the entire Danish population, 780,547 children were followed from birth (January
      1, 1997 to December 31, 2008) until December 31, 2012. We calculated adjusted
      hazard ratios and absolute risks of autism with 95% confidence intervals (CIs)
      related to previous otitis media diagnoses and antibiotic prescriptions redeemed
      at Danish pharmacies. The absolute risk of autism before age 10 was increased
      among children with otitis media (1.2% for females and 3.3% for males) and in
      children who had redeemed an antibiotic prescription (0.6% and 2.7% for females
      and males) compared to children without a history of otitis media and antibiotics
      usage (0.4% for females and 1.9% for males). Similarly, we found an increased
      hazard ratio of autism associated with otitis media (1.83 95% CI 1.71-1.95) and
      antibiotics usage (1.29 95% CI 1.17-1.43). A history of both otitis media and
      antibiotic treatment did not further increase the risk of autism. Although the
      risk of autism was associated with otitis media and treatment with antibiotics,
      we found little evidence of a synergistic effect between otitis media infections
      and treatment with antibiotics. Autism Res 2018, 11: 1432-1440. (c) 2018
      International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY:
      We investigated whether otitis media ear infections and antibiotic treatment were
      associated with autism spectrum disorder. Autism was more common in children who
      had had an otitis media infection or who had been treated with antibiotics. Given
      the observational nature of our data, our study cannot be used to conclude that
      otitis media or use of antibiotics cause autism, as our findings may be subject
      to unobserved confounding.

PMID- 30284387
TI  - Mutations in the NOD2 gene are associated with a specific phenotype and lower
      anti-tumor necrosis factor trough levels in Crohn's disease.
AB  - OBJECTIVE: Nucleotide-binding oligomerization domain-containing protein 2 (NOD2)
      gene mutations are known to be an important risk factor in the pathogenesis of
      Crohn's disease (CD). Specific disease phenotypes are associated with the
      presence of NOD2 gene mutation. One treatment option is to use an anti-tumor
      necrosis factor (TNF)-alpha agent. Therapeutic drug monitoring (TDM) is usually
      performed in cases of a loss of response. Our aim was to explore whether NOD2
      gene mutations have an effect on the disease phenotype, vitamin D levels, and on
      TDM in CD patients. METHODS: This was a retrospective genotype-phenotype
      association study on NOD2 gene mutations in 161 patients with CD. RESULTS:
      Altogether 55 (34.2%) patients carried at least one mutant allele of NOD2. NOD2
      gene mutations were associated with ileocecal disease, ileocecal resection,
      stricturing and perianal disease, and patients with NOD2 gene mutation had
      significantly less frequent colonic disease and received an ostomy less
      frequently. TDM in patients with NOD2 gene mutation showed more frequent anti-TNF
      trough levels in the subtherapeutic range and lower anti-TNF trough levels than
      in NOD2 wild-type (WT) patients. CONCLUSIONS: CD patients with NOD2 gene mutation
      have a specific clinical phenotype and they may require higher doses of anti-TNF
      agents to achieve sufficient anti-TNF trough levels. They may therefore benefit
      from a proactive TDM than a reactive approach. This could be another step in the
      direction of personalized medicine.

PMID- 30284388
TI  - Vitrectomy with silicone oil tamponade for retinal detachment associated with
      giant retinal tears: Favourable outcomes without adjuvant scleral buckling.
AB  - PURPOSE: To evaluate the outcomes of pars plana vitrectomy with silicone oil
      tamponade in the management of retinal detachment associated with giant retinal
      tears. METHODS: We reviewed 45 eyes of 42 patients with primary retinal
      detachment associated with giant retinal tears over 10 years at a tertiary
      referral centre. Patients underwent 23-gauge vitrectomy without adjuvant scleral
      buckling by a single surgeon and had follow-up at least 6 months after silicone
      oil removal. RESULTS: Mean follow-up was 37 +/- 35 months. Seven eyes (16%) had
      grade C proliferative vitreoretinopathy, and 16 (36%) had a giant retinal tear
      >=180 degrees  at baseline. The primary reattachment rate was 84%, and the
      overall final anatomical success rate was 98%. The mean Snellen visual acuity
      equivalent at the final visit was 20/58. Final visual acuity >=20/40 was achieved
      in 64%. The mean duration of silicone oil tamponade was 10.5 +/- 4 weeks. By the
      final visit, silicone oil had been removed from 44 eyes (98%). CONCLUSION: The
      high rates of anatomical and functional success support management of giant
      retinal tears-associated retinal detachment with vitrectomy without adjuvant
      scleral buckling. Removal of silicone oil at the earliest possible time helps to
      avoid complications such as keratopathy, glaucoma and visual loss without
      apparent reason.

PMID- 30284389
TI  - Adenoid cystic carcinoma: A study of 19 cases of salivary and extra-salivary
      tumours diagnosed by fine needle aspiration cytology.
AB  - BACKGROUND: Adenoid cystic carcinoma (ACC) arises at sites where seromucinous or
      sweat gland epithelium is present and commonly affects the salivary glands.
      Rarely it can occur at extra-salivary locations. METHODS: A retrospective
      analysis of 19 cases of ACC diagnosed on fine needle aspiration cytology (FNAC)
      over a period of 15 y (2002-2016) was made. RESULTS: Of 19 total cases, there
      were 10 salivary and 9 extra-salivary ACCs. Extra-salivary tumours were seen in 2
      cases each in trachea, tongue and in one case each in bronchus, lung,
      subcutaneous tissue, maxillary antrum, and external auditory canal. The age
      ranged from 14-80 y (mean: 49.5 y), 10 patients were male and 9 were female. The
      smears were highly cellular in 11 cases, moderately cellular in 5 cases while 3
      cases were paucicellular. Multilayered dense clusters, tissue fragments,
      dispersed cells and cup-shaped fragments were seen. Relatively uniform cells with
      high nuclear: cytoplasmic ratio, hyperchromatic nuclei, irregular margins, and
      nuclear moulding were observed. Variable sized hyaline globules, finger-like
      hyaline material, hyaline cylinders, and hyaline cords were noted. The cytologic
      diagnosis of ACC was rendered in 13 cases while in 6 cases it was one of the
      differential diagnosis including monomorphic adenoma, membranous variant of basal
      cell adenoma, adnexal tumour, polymorphous adenocarcinoma, and pleomorphic
      adenoma (PA). CONCLUSIONS: Cytologists must be aware of varied locations where
      ACC can occur. A diagnosis of ACC must not rely exclusively on the occurrence of
      hyaline globules but necessitates a close scrutiny of cellular and nuclear
      features to avoid diagnostic pitfalls.

PMID- 30284391
TI  - Fine needle aspiration biopsy cytology of phyllodes tumour and fibroadenoma: A
      cytomorphological study of 104 cases.
AB  - BACKGROUND: The cytomorphological features in the distinction between phyllodes
      tumour (PT) and fibroadenoma (FA) on fine needle aspiration biopsy (FNAB) remains
      challenging because of the biphasic nature of these lesions and the rarity of PT.
      METHODS: FNAB smears of histologically confirmed PT (N = 26) and FA (N = 78)
      cases were retrieved from a retrospective database interrogation from the
      Department of Cytology/Tissue Pathology, ICPMR Pathology West (Cerner Millennium)
      in Westmead Hospital. For each case, two smears were selected, de-identified and
      independently reviewed by four observers comprising two cytologists and two
      cytopathologists. Cytological parameters examined included detailed evaluation of
      smear cellularity, epithelial and stromal components as well as the smear
      background. RESULTS: The cytological features of moderate to marked stromal
      cellularity and stromal nuclear atypia were more evident in PT than in FA,
      identified by three out of four observers. The epithelial characteristics,
      presence of macrophages, multinucleated giant cells and blood vessels showed no
      statistically significant differences in the distinction between the two lesions.
      CONCLUSION: The results of this study indicate that in all of the cytological
      features assessed for PT and FA, no single cytological feature was found to be
      statistically significant in identifying PT across all observers. This reflects
      the overlap of cytological features seen in these lesions. FNAB cytology cannot
      reliably distinguish FA and PT.

PMID- 30284390
TI  - Application of a novel in vivo imaging approach to measure pulmonary vascular
      responses in mice.
AB  - Noninvasive imaging of the murine pulmonary vasculature is challenging due to the
      small size of the animal, limits of resolution of the imaging technology,
      terminal nature of the procedure, or the need for intravenous contrast. We report
      the application of laboratory-based high-speed, high-resolution x-ray imaging,
      and image analysis to detect quantitative changes in the pulmonary vascular tree
      over time in the same animal without the need for intravenous contrast. Using
      this approach, we detected an increased number of vessels in the pulmonary
      vascular tree of animals after 30 min of recovery from a brief exposure to
      inspired gas with 10% oxygen plus 5% carbon dioxide (mean +/- standard deviation:
      2193 +/- 382 at baseline vs. 6177 +/- 1171 at 30 min of recovery; P < 0.0001). In
      a separate set of animals, we showed that the total pulmonary blood volume
      increased (P = 0.0412) while median vascular diameter decreased from 0.20 mm
      (IQR: 0.15-0.28 mm) to 0.18 mm (IQR: 0.14-0.26 mm; P = 0.0436) over the
      respiratory cycle from end-expiration to end-inspiration. These findings suggest
      that the noninvasive, nonintravenous contrast imaging approach reported here can
      detect dynamic responses of the murine pulmonary vasculature and may be a useful
      tool in studying these responses in models of disease.

PMID- 30284392
TI  - High-throughput doping control analysis of 28 amphetamine-type stimulants in
      equine plasma using hydrophilic interaction liquid chromatography-tandem mass
      spectrometry.
AB  - A hydrophilic interaction liquid chromatography-tandem mass spectrometry method
      (HILIC-MS/MS) was developed for the simultaneous determination of 28 amphetamine
      type stimulants (ATSs) in equine plasma for doping control analysis. In this
      method, stimulants were recovered from equine plasma by liquid-liquid extraction
      (LLE) at pH 9.5 using methyl tert-butyl ether and detected on a Thermo Finnigan
      triple quadrupole mass spectrometer operating in positive-ion mode electrospray
      ionization. All stimulants were eluted within 7 minutes and baseline separation
      was achieved for isomeric and isobaric compounds using HILIC chromatography.
      Extraction efficiency was greater than 80% and matrix effect was acceptable for
      most stimulants. The limit of detection (LOD) was in the range of 10-50 pg/mL and
      the lower limit of quantification (LLOQ) was in the range of 50-100 pg/mL.
      Quadratic regression was employed for quantification and the dynamic range of
      quantification was 50-10000 pg/mL. Confirmatory analysis criteria were
      established using product ion ratios and retention time. The limit of
      confirmation (LOC) was in the range of 20-100 pg/mL. Stability study results
      indicated that some stimulants were unstable in equine plasma at room temperature
      and 4 degrees C. However, all the stimulants studied were stable at -20 degrees C
      and - 80 degrees C for the 6 month study period.

PMID- 30284395
TI  - High rate of failed visual-acuity measurements with the Amsterdam Picture Chart
      in screening at the age of 36 months.
AB  - PURPOSE: In the Netherlands, youth health care physicians and nurses screen all
      children for general health disorders at Child Health Care Centers. As part of
      this, the eyes are screened seven times, with the first visual acuity (VA)
      measurement at 36 months with the Amsterdam Picture Chart (APK). The suitability
      of the APK has been questioned. METHODS: Children born between July 2011 and June
      2012 born in the provinces Drenthe, Gelderland and Flevoland and invited for
      screening at 36 months were eligible. Parents were sent the APK picture optotypes
      to practise with their children in advance. Data were collected from electronic
      screening records. The Dutch vision screening guideline prescribes that children
      with VA <5/6, or one line interocular difference (not logMAR, however) should be
      retested or referred. RESULTS: Of 10 809 eligible children, 1546 did not attend
      and 602 attended but had no VA measurement at age 36 months, 247 of these were
      under orthoptic treatment. Of the 8448 children examined, VA was sufficient in
      5663 (67.0%) and insufficient in 1312 (15.5%). In 1400 (16.6%), the measurement
      of VA itself failed. In 73 (0.9%), data were missing. Of the 216 children with 2
      failed VA measurements, 150 (69%) were not referred, and measurement of VA was
      deferred to the next general screening examination at 45 months. CONCLUSION:
      Although most parents had practised the APK picture optotypes at home with their
      children, the rate of failed APK measurements plus the measurements with
      insufficient VA was 32.1% at 36 months. Similar rates have previously been
      reported for Lea Symbols and HOTV, permitting the conclusion that measurement of
      VA at the age of 36 months cannot be recommended as a screening test in the
      general population.

PMID- 30284393
TI  - Postoperative management in cataract surgery: nepafenac and preservative-free
      diclofenac compared.
AB  - PURPOSE: Current cataract surgery guidelines recommend routine use of topical
      nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing pseudophakic cystoid
      macular oedema (PCME). Here, we compare the clinical efficacy and tolerability of
      two potent NSAIDs, nepafenac and preservative-free diclofenac following cataract
      surgery. METHODS: Randomized, double-blind, prospective single-centre study.
      Ninety-six eyes of 95 patients undergoing routine cataract surgery were
      randomized 1:1 either to nepafenac (Nevanac, 1 mg/ml) or diclofenac (Dicloabak, 1
      mg/ml) for 3 weeks. Seventy-three patients accounting for 73 eyes completed the
      entire follow-up. Aqueous flare and central retinal thickness (CRT) analysis were
      conducted preoperatively and at control visits 28 days and 3 months after
      surgery. A structured home questionnaire and interview were used to record any
      adverse effects of the topical medications, subjective visual recovery and the
      dispenser's ease of use. RESULTS: No differences were observed between the groups
      for aqueous flare, CRT, speed of recovery or visual acuity gain. Seven patients
      (16%) on nepafenac and 20 patients (48%) on preservative-free diclofenac reported
      symptoms related to topical use of NSAID medications (p = 0.001). CONCLUSION: No
      differences in clinical efficacy were found between potent NSAIDs, while
      tolerability might be an issue.

PMID- 30284394
TI  - Association between schizophrenia and autism spectrum disorder: A systematic
      review and meta-analysis.
AB  - Schizophrenia and autism spectrum disorder (ASD) are significant public health
      problems. Scientists have recently explored the association between schizophrenia
      and ASD, but the findings are inconsistent. Thus, we conducted a systematic
      review and meta-analysis of epidemiological studies to examine the association
      between schizophrenia and ASD. PubMed, Embase, and the Cochrane Library were used
      for literature searches to identify eligible studies published in English before
      October 2, 2017. Relevant studies estimating the association between
      schizophrenia and ASD were included. The meta-analysis of the prevalence of
      schizophrenia in individuals with ASD encompassed 1,950,113 participants and
      14,945 individuals with ASD. A random-effects model was chosen to synthesize the
      effect sizes of individual studies. The prevalence of schizophrenia was
      significantly higher in individuals with ASD than in controls (odds ratio = 3.55,
      95% confidence interval: 2.08-6.05, P < .001). Both sensitivity analysis and
      publication bias testing revealed that the findings were robust. The systematic
      review of the prevalence of ASD in individuals with schizophrenia encompassed 930
      participants. The prevalence of ASD in individuals with schizophrenia ranged from
      3.4 to 52%. The systematic review and meta-analysis showed a significant
      association between schizophrenia and ASD. Autism Research 2018, 11: 1110-1119.
      (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY
      SUMMARY: This systematic review and meta-analysis explored the association
      between schizophrenia and ASD. We found that the prevalence of schizophrenia was
      significantly higher in individuals with ASD than in controls and the prevalence
      of ASD in individuals with schizophrenia ranged from 3.4 to 52%. A comprehensive
      estimation of schizophrenia and ASD has important implications for the diagnosis,
      treatment, prognosis, and development of a fundamental understanding of these
      disorders.

PMID- 30284396
TI  - Histological basis for the variability of visual field defects in early glaucoma.

PMID- 30284398
TI  - Controlled Formation of a Main Chain Supramolecular Polymer Based on Metal-Ligand
      Interactions and a Thiol-Ene Click Reaction.
AB  - Supramolecular polymers with multiple functionalities and hierarchical structures
      have received considerable attention and become a hot research topic over the
      past years. Herein, a main-chain supramolecular polymer has been successfully
      fabricated by using metal-ligand interactions and a thiol-ene click reaction. 1 H
      NMR, UV/Vis, DOSY, and viscosity measurements were carried out to investigate the
      molecular recognition and the process of supramolecular polymerization. From the
      study, the orthogonality between thiol-ene click reactions and the terpyridine
      metal ions complexation behavior was testified, and supramolecular polymeric
      assemblies could be constructed by a one pot method. In the meantime, due to the
      incorporation of metal-ligand interactions, the supramolecular polymer shows
      stimuli-responsive properties toward chemical stimuli. Hence, this work could
      provide a methodology for developing supramolecular polymers as smart materials.

PMID- 30284397
TI  - A1899, PK-THPP, ML365, and Doxapram inhibit endogenous TASK channels and excite
      calcium signaling in carotid body type-1 cells.
AB  - Sensing of hypoxia and acidosis in arterial chemoreceptors is thought to be
      mediated through the inhibition of TASK and possibly other (e.g., BKC a )
      potassium channels which leads to membrane depolarization, voltage-gated Ca
      entry, and neurosecretion. Here, we investigate the effects of pharmacological
      inhibitors on TASK channel activity and [Ca2+ ]i -signaling in isolated neonatal
      rat type-1 cells. PK-THPP inhibited TASK channel activity in cell attached
      patches by up to 90% (at 400 nmol/L). A1899 inhibited TASK channel activity by
      35% at 400 nmol/L. PK-THPP, A1899 and Ml 365 all evoked a rapid increase in type
      1 cell [Ca2+ ]i . These [Ca2+ ]i responses were abolished in Ca2+ -free solution
      and greatly attenuated by Ni2+ (2 mM) suggesting that depolarization and voltage
      gated Ca2+ -entry mediated the rise in [Ca2+ ]i. Doxapram (50 MUmol/L), a
      respiratory stimulant, also inhibited type-1 cell TASK channel activity and
      increased [Ca2+ ]i. . We also tested the effects of combined inhibition of BKC a
      and TASK channels. TEA (5 mmol/L) slightly increased [Ca2+ ]i in the presence of
      PK-THPP and A1899. Paxilline (300 nM) and iberiotoxin (50 nmol/L) also slightly
      increased [Ca2+ ]i in the presence of A1899 but not in the presence of PK-THPP.
      In general [Ca2+ ]i responses to TASK inhibitors, alone or in combination with
      BKC a inhibitors, were smaller than the [Ca2+ ]i responses evoked by hypoxia.
      These data confirm that TASK channel inhibition is capable of evoking membrane
      depolarization and robust voltage-gated Ca2+ -entry but suggest that this, even
      with concomitant inhibition of BKC a channels, may be insufficient to account
      fully for the [Ca2+ ]i -response to hypoxia.

PMID- 30284399
TI  - Effects of using lubricant during the speculum examination for Pap smear
      collection.
AB  - OBJECTIVE: To evaluate the effect of using lubricant during speculum examination
      for Pap smear collection. METHODS: A cross-sectional study was conducted
      involving 83 patients attending a medical school clinic. Participants were
      allocated into two groups: Group 1-Lubricant using; Group 2-No lubricant using.
      All patients were submitted to two successive collections and after were asked
      about their level of discomfort. Differences between groups regarding quality,
      artifacts, cytology, and level of discomfort were observed through chi-squared
      test. Odds ratios and 95% confidence intervals were also estimated. Statistical
      significance was set at P < .05. RESULTS: No significant differences between
      groups regarding quality, presence of artifacts, and cytological results were
      observed. Significant lower discomfort level in Group 1 (lubricant using).
      CONCLUSION: The use of vaginal lubricant did not affect the results of cytology
      and could be a useful tool to reduce the discomfort during Pap smear collection.

PMID- 30284402
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 41/2018.

PMID- 30284401
TI  - Detection of aquaporin-4 antibodies for patients with CNS inflammatory
      demyelinating diseases other than typical MS in Lithuania.
AB  - OBJECTIVES: Neuromyelitis optica (NMO) is frequently associated with aquaporin-4
      autoantibodies (AQP4-Ab); however, studies of NMO in Lithuania are lacking.
      Therefore, the main objective of our study is to assess positivity for AQP4-Ab in
      patients presenting with inflammatory demyelinating central nervous system (CNS)
      diseases other than typical multiple sclerosis (MS) in Lithuania. MATERIALS AND
      METHODS: Data were collected from the two largest University hospitals in
      Lithuania. During the study period, there were 121 newly diagnosed typical MS
      cases, which were included in the MS registry database. After excluding these
      typical MS cases, we analyzed the remaining 29 cases of other CNS inflammatory
      demyelinating diseases, including atypical MS (n = 14), acute transverse
      myelitis, TM (n = 8), acute disseminated encephalomyelitis, ADEM (n = 3),
      clinically isolated syndrome, CIS (n = 2), atypical optic neuritis, ON (n = 1),
      and NMO (n = 1). We assessed positivity for AQP4-Ab for the 29 patients and
      evaluated clinical, laboratory, and instrumental differences between AQP4-Ab
      seropositive and AQP4-Ab seronegative patient groups. RESULTS: AQP4-Ab test was
      positive for three (10.3%) patients in our study, with initial diagnoses of
      atypical MS (n = 2) and ADEM (n = 1). One study patient was AQP4-Ab negative
      despite being previously clinically diagnosed with NMO. There were no significant
      clinical, laboratory, or instrumental differences between the groups of AQP4-Ab
      positive (3 [10.3%]) and negative (26 [89.7%]) patients. CONCLUSIONS: AQP4-Ab
      test was positive for one-tenth of patients with CNS inflammatory demyelinating
      diseases other than typical MS in our study. AQP4-Ab testing is highly
      recommended for patients presenting with not only TM and ON but also an atypical
      course of MS and ADEM.

PMID- 30284400
TI  - Effect of a 9-week exercise training regimen on expression of developmental genes
      related to growth-dependent fat expansion in juvenile rats.
AB  - This study examined the association between changes in mRNA expression of
      development-related genes including those of the homeobox (Hox) family and growth
      dependent increases in inguinal, mesenteric, and epididymal white adipose tissue
      (WAT) at 4, 6, 10, and 14 weeks of age in rats. We also examined the effects of a
      9-week exercise training regimen starting at 5 weeks of age on the mRNA levels of
      the genes of interest. HoxC8, HoxC9, Gpc4, Bmpr1a, Ppargamma, Pgc1alpha, Adrb3,
      Hsl, leptin, and adiponectin in each type of WAT - except HoxA5, Gpc4, and
      Pgc1alpha in epididymal - showed a positive association between WAT weights and
      WAT mRNA levels; however, the slope of the regression lines exhibited fat depot
      specific differences. HoxA5 showed no significant association, and Gpc4 and
      Pgc1alpha showed a negative association in epididymal WAT. After exercise
      training, the mean HoxA5, HoxC8, HoxC9, HoxC10, Gpc4, Ppargamma, and Pgc1alpha
      mRNA levels in inguinal WAT were outliers on the regression line between mean
      mRNA level and WAT weight in control rats - that is, mean HoxA5 and Pgc1alpha
      mRNA level was higher, whereas HoxC8, HoxC9, HoxC10, Gpc4, and Ppar levels were
      lower in exercise-trained rats than in same-age controls. Ppargammagamma and
      adiponectin levels were upregulated in epididymal WAT, while HoxA5 was
      downregulated, but HoxC9, Gpc4, Ppargamma, and adiponectin levels were
      upregulated in mesenteric WAT. These results suggest that some of the
      developmental genes tested may have fat depot-specific roles in the growth
      dependent expansion of WAT, and that Hox genes that are activated in response to
      exercise training also vary among different WAT types.

PMID- 30284403
TI  - Predicting the outcome of laser peripheral iridotomy for primary angle closure
      suspect eyes using anterior segment optical coherence tomography.
AB  - PURPOSE: Develop an algorithm to predict the success of laser peripheral
      iridotomy (LPI) in primary angle closure suspect (PACS), using pretreatment
      anterior segment optical coherence tomography (ASOCT) scans. METHODS: A total of
      69 eyes with PACS underwent LPI and time-domain ASOCT scans (temporal and nasal
      cuts) were performed before and after LPI. After LPI, success is defined as one
      or more angles changed from closed to open. All the pretreatment ASOCT scans were
      analysed using the Anterior Segment Analysis Program to derive anterior chamber
      angle (ACA) measurements. The measurements for each angle were ordered along with
      angle-independent measurements totalling to 42 measurements which serve as
      features for the prediction algorithm. Two masked glaucoma fellowship-trained
      ophthalmologists graded the pre-LPI ASOCT scans to determine whether LPI was
      likely to successful. RESULTS: There were 42 (60.9%) eyes that fulfilled the
      criteria for success after LPI. Iris concavity, angle recess area (750 MUm) and
      iris concavity ratio showed the highest predictive score and were selected using
      correlation-based subset selection method. These features were classified into
      two ('successful' and 'unsuccessful') categories using a Bayes classifier. The
      algorithm predicted the success of LPI with 79.28% cross validation accuracy,
      which was superior to the predictive accuracy of the ophthalmologists (kappa
      0.497 and 0.636 respectively). CONCLUSION: Using pretreatment ASOCT scans, our
      algorithm was superior to ophthalmologists in predicting the success of LPI for
      PACS eyes. This novel algorithm could aid decision making in offering LPI as a
      prophylaxis for PACS.

PMID- 30284404
TI  - Synthesis and antifungal activities of novel thiophene-based stilbene derivatives
      bearing an 1,3,4-oxadiazole unit.
AB  - BACKGROUND: Natural stilbenes (especially resveratrol and its derivatives) are
      well-known phytoalexins that are active against many plant diseases. However,
      oxidative degradation and low bioavailability limit their exogenous application
      as fungicides on crops. In this study, a new class of resveratrol-inspired
      thiophene-based stilbene derivatives bearing an 1,3,4-oxadiazole unit was
      synthesized and the derivatives' antifungal activities against phytopathogenic
      fungi were investigated. RESULTS: The results revealed that compounds 5h and 5j
      exhibited improved antifungal activity against Botrytis cinerea with median
      effective concentrations (EC50 ) of 168.5 and 155.4 ug mL-1 , respectively, which
      were superior to the EC50 of resveratrol (263.1 ug mL-1 ). Compound 5j was shown
      to effectively control disease development in B. cinerea-infected tomatoes in
      vivo. Notably, considerably abnormal mycelial morphology and increased cell
      membrane conductivity were observed in the presence of compound 5j. CONCLUSION: A
      new class of thiophene-containing stilbene derivatives was designed and
      synthesized. Bioassay results showed that compound 5j exhibited promising
      antifungal activity, suggesting practical potential for fungal disease control.
      (c) 2018 Society of Chemical Industry.

PMID- 30284406
TI  - Pancreatic mixed acinar-neuroendocrine carcinoma, a unique diagnostic challenge
      on FNA cytology: A small series of two cases with literature review.
AB  - Mixed acinar-neuroendocrine carcinoma (MANEC) of the pancreas is a rare tumor. We
      present two cases of MANEC diagnosed on endoscopic ultrasound (EUS) guided fine
      needle aspiration (FNA). The first patient is a 33-year-old male who had a 3.6 cm
      mass in the uncinate process and liver metastasis. The second patient is a 66
      year-old male with a 10 cm mass in the pancreatic tail. The FNA smears from both
      cases were hypercellular with neoplastic cells in loosely cohesive clusters and
      many naked nuclei. In both cases, the tumor cells were positive for CKAE1/3,
      synaptophysin, chromogranin, and trypsin by immunohistochemistry. Final diagnoses
      of MANEC were rendered based on cytological features and immunohistochemical
      profiles. To date, 44 cases of MANEC have been reported in the English
      literature, only three of which were diagnosed on cytopathology specimens before
      surgical resection. Our report adds two more cases diagnosed on cytopathology
      alone. Herein, we discuss the various cytomorphologic and clinical features of
      MANEC and present a brief review of the literature. Diagn. Cytopathol.

PMID- 30284407
TI  - Detection of secondary choroidal neovascularization in chronic central serous
      chorioretinopathy by swept source-optical coherence tomography angiography.

PMID- 30284405
TI  - Clinical performance of the Cobas 4800 HPV test and the Aptima HPV assay in the
      management of women referred to colposcopy with minor cytological abnormalities.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical performance of the
      Cobas 4800 HPV test and the Aptima HPV assay for the detection of CIN2+ disease
      in women referred to colposcopy with minor cytological abnormalities. METHODS:
      ThinPrep liquid-based cytology samples were collected from 562 women referred to
      colposcopy with minor cytological abnormalities. HPV testing by both assays was
      performed on these samples. Clinical performances for detection of histologically
      diagnosed CIN2+ and CIN3+ were calculated. RESULTS: HPV prevalence by the Cobas
      4800 HPV test was 58.2% and 53.0% women tested positive with the Aptima HPV assay
      in the entire study population. The Aptima HPV assay and the Cobas 4800 HPV test
      displayed equivalent sensitivity of 90.2% (95%CI, 83.4-94.9) for the detection of
      CIN2+ disease. However, the Aptima HPV assay displayed greater specificity of
      61.0% (95% CI, 54.0-68.0) when compared to the Cobas 4800 HPV test 53.0% (95% CI,
      46.0-60.0), and this was significantly higher (P = .0004). The Aptima HPV assay
      also displayed higher specificity 76.5% (95% CI, 66.0-85.0) in the ASCUS category
      in comparison to the Cobas 4800 HPV test 65.0% (95% 54.0-75.0) which was
      statistically significant (P = .004). CONCLUSIONS: Both the tests displayed
      similar sensitivity. However, the Aptima HPV assay was significantly more
      specific in the identification of women with CIN2+ disease in a colposcopy
      referral population.

PMID- 30284408
TI  - Disc haemorrhages in Polish Caucasian patients with normal tension glaucoma.
AB  - AIM: The aim of this observational study was to evaluate the epidemiology of disc
      haemorrhages (DH) in Polish patients with normal tension glaucoma (NTG) and their
      association with some risk factors. MATERIAL AND METHODS: The group studied
      consisted of 274 Caucasian patients with NTG (410 eyes) divided into those with
      disk haemorrhages (DH+, = 94 eyes in 81 patients) and those without disc
      haemorrhages (DH-, = 316 eyes in 193 patients). Ophthalmic examinations with
      visual field (VF) testing were carried out in these patients every 3 months for
      at least 18 months. The medical history was recorded taking glaucoma, other
      ophthalmic diseases, chronic general disorders and vascular risk factors into
      account. RESULTS: Unilateral and bilateral DH were observed more frequently in
      women (p = 0.0010). Maximum IOP was significantly higher in the DH+ group (p =
      0.000026). Notches and peripapillary atrophy were found with similar frequency in
      DH+ and DH- patients (p = 0.4631). The mean defect (MD) in the VF at the time of
      diagnosis was lower in the DH+ group (-6.27 dB) than in the DH group (-10.14 dB),
      (p = 0.000055). The initial MD in the DH+ group had a positive correlation with
      maximum initial IOP. A progressive loss of VF was observed in 206 eyes with NTG
      (50.2%), with a mean of 0.72 dB/year. The progression was more frequent in DH+
      patients (78.4% versus 41.1%), but there were no statistically significant
      differences in the rate of progression between DH+ and DH- patients (p = 0.46).
      The morphology of early scotoma depended on the presence of DH (p < 0.00001), and
      early scotoma in the DH+ group was more frequently localized paracentrally. There
      was a significant difference in a number of antiglaucoma drops between DH+ and DH
      patients (p < 0.00001). There were no differences in the frequency of migraines
      between both groups (p = 0.31). General hypotension was observed with similar
      frequency in the DH+ DH- groups (p = 0.3). General hypertension was less frequent
      in DH+ patients (p = 0.041), especially in women (p = 0.000027). Diabetes
      mellitus (DM) was significantly less frequent (21.3%) in patients with DH+ (3.7%)
      than in the DH- group (p = 0.000852), especially among the women (p = 0.000216).
      CONCLUSION: In our study, DH were more frequent both unilaterally and bilaterally
      in women. Initial intraocular pressure (IOP) was higher in NTG patients with DH,
      and early scotoma was localized in the paracentral area of the VF. Disc
      haemorrhages (DH) were less frequent in women with general hypertension and with
      diabetes mellitus.

PMID- 30284409
TI  - Supercritical Fluid-Assisted Porous Microspheres for Efficient Delivery of
      Insulin and Inhalation Therapy of Diabetes.
AB  - Pulmonary delivery of drugs has attracted increasing attention in healthcare, as
      the lungs are an easily accessible site for noninvasive systemic delivery of
      drugs. Although pulmonary inhalation of porous microparticles has been shown to
      sustain drug delivery, there are limited reports on efficient delivery of insulin
      and inhalation therapy of diabetes based on supercritical carbon dioxide (SC-CO2
      ) technology. Herein, this study reports the fabrication of insulin-loaded poly-l
      lactide porous microspheres (INS-PLLA PMs) by using the SC-CO2 technology, and
      their use as an inhalation delivery system potentially for diabetes therapy.
      Biocompatibility and delivery efficiency of the PLLA PMs in the lungs are
      investigated. The PLLA PMs show negligible toxicity to lung-derived cells,
      resulting in no significant reduction in cell viability, as well as levels of
      various inflammatory mediators such as interleukin (IL)-6, IL-8, and tumor
      necrosis factor-alpha, compared with the negative control group. INS-PLLA PMs are
      further efficiently deposited in the trachea and the bronchi of superior lobes of
      the lungs, which exhibit pronounced hypoglycemic activity in induced diabetic
      rats. Together, the results demonstrate that the INS-PLLA PMs have a strong
      potential as an effective strategy for inhalation treatment of diabetes.

PMID- 30284410
TI  - Immunohistochemical analysis of OTP and NKX6.1 in neuroendocrine tumors of the
      lung and pancreas.
AB  - BACKGROUND: Homeobox transcription factors have demonstrated utility in
      diagnosing neuroendocrine tumors. Orthopedia homeobox protein (OTP) has a well
      defined role in embryonic neurodevelopment and has also been described as a
      prognostic marker in lung neuroendocrine tumors (NET). Additionally, NK6 homeobox
      1 (NKX6.1) has been described to be necessary for the development of
      neuroendocrine cells in the pancreas. We evaluated immunohistochemical (IHC)
      expression of OTP and NKX6.1 to determine their utility in the diagnosis of NETs
      from lung and pancreas fine-needle aspirations (FNA). METHODS: Our study examined
      50 FNA specimens, including 30 primary pulmonary NETs (8 carcinoid tumors (CT), 6
      atypical carcinoids (AC), 11 small-cell neuroendocrine carcinomas (SCNEC), 5
      large-cell neuroendocrine carcinomas (LCNEC)) and 20 primary pancreatic NETs (17
      well-differentiated pancreatic neuroendocrine tumors (PanNET) and 3 poorly
      differentiated pancreatic neuroendocrine carcinomas (PanNEC)). IHC expression of
      OTP, NKX6.1, and Ki-67 was evaluated on FNA cell blocks. RESULTS: Half of the
      pulmonary TC tumors expressed OTP, while only 17% of AC and 20% of LCNEC
      expressed OTP. Neither SCNECs nor any pancreatic NET expressed OTP. In contrast,
      intermediate and high-grade tumors expressed NKX6.1 (LCNEC-80%, SCNEC-82%, and AC
      83%) more often than low-grade tumors (TC-63%, PanNET-71%). All three PanNECs
      expressed NKX6.1. CONCLUSIONS: OTP may be useful in diagnosing well
      differentiated NETs of pulmonary origin. NKX6.1 may have utility in segregating
      high from low-grade NETs of both pulmonary and pancreatic origin, although other
      methods will be required to determine site of origin.

PMID- 30284411
TI  - Change in choroidal volume after dexamethasone intravitreal implant in eyes with
      diabetic macular oedema.

PMID- 30284412
TI  - Clinical evidence supporting the use of donor sclera as spacer material in
      complicated cases of strabismus surgery - retrospective evaluation of surgical
      results in 117 patients with thyroid-associated ophthalmopathy or congenital
      strabismus.
AB  - PURPOSE: To examine the outcome of the use of donor sclera as spacer material in
      complicated cases of strabismus surgery. METHODS: A retrospective cohort study on
      patients with complicated thyroid-associated ophthalmopathy (TAO) (n = 42) or
      congenital strabismus (n = 75). Patients underwent strabismus surgery during 1994
      2014. The surgical results were evaluated in terms of the reduction in the angle
      of deviation, the need for re-operation, complications and patient satisfaction.
      RESULTS: The majority of the TAO patients underwent surgery for vertical
      strabismus (n = 25). The vertical angle of deviation in the primary position was
      significantly reduced from a median of 23 prism dioptres (PD) to 2 PD (n = 35, p
      < 0.001). The horizontal angle of deviation in primary position for TAO patients
      with esotropia was significantly reduced, from a median of 35 PD to 2 PD (n = 17,
      p < 0.001). The majority of the congenital cases had horizontal strabismus
      (esotropia = 29, exotropia = 27). The angle of deviation in esotropia was reduced
      from a median of 29 PD to 8 PD (n = 36, p < 0.001) and in exotropia from 30 PD to
      10 PD (n = 34, p < 0.001). Most of the patients were satisfied with the outcome
      of surgery, and only 12% required re-operation within 2 years. CONCLUSION: This
      is the first clinical study on the use of donor sclera as spacer material in
      complicated cases of strabismus surgery. The surgical results were good in terms
      of the reduction in the angle of deviation, the need for re-operation,
      complications and patient satisfaction, supporting the use of donor sclera for
      strabismus surgery.

PMID- 30284413
TI  - Morphological changes in the diseased retina on a healthy choroid-retinal pigment
      epithelial complex after full macular translocation for exudative age-related
      macular degeneration.
AB  - PURPOSE: To describe the change in the retinal morphology after full macular
      translocation (FMT) for exudative age-related macular degeneration (AMD) and
      identify predictive factors for the visual outcome. METHODS: All patients who
      underwent FMT from December 2008 through July 2013 were selected. Exclusion
      criteria were FMT for other disease than AMD, age <60 years, <12 months of follow
      up or no available images. Spectral domain optical coherence tomography, fundus
      autofluorescence, fluorangiography and indocyanine green angiography were
      evaluated. RESULTS: In total, 51 patients were included with a mean follow-up of
      30 months. The presence of the external limiting membrane (ELM) was a significant
      predictor for a favourable visual outcome 1 year after FMT (OR = -0.30). Other
      significant predictive factors were the absence of intraretinal fluid (OR = 0.28)
      and the mixed choroidal neovascularization type (OR = -0.47), whereas
      nonresponders (OR = 0.41) and fibrotic lesions (OR = 0.35) were less likely to
      have a good visual function after surgery. CONCLUSION: Full macular translocation
      (FMT), that permits to relocate the diseased macula onto an area of unaffected
      retinal pigment epithelial and choroid, can restore the anatomy and visual
      function in some patients with AMD when the outer retina layers are not
      irreversibly damaged. The presence of the ELM seems to be the most reliable
      factor in predicting the functional outcome.

PMID- 30284415
TI  - [HEPATOCELLULAR CARCINOMA. GENDER ASPECTS OF CARCINOGENESIS].
AB  - The article reviews contemporary data about influences of sex hormons
      (androgenes, estrogenes) and their nuclear receptors on development of
      hepatocellular carcinoma. Use of hepatoprotective drugs for treatment of chronic
      liver diseases and prophylactic of hepatocellular carcinoma should be correlated
      with potential hormonal effects of the treatment.

PMID- 30284416
TI  - MELD SCORE CORRELATION WITH LABORATORY FINDINGS AND COMPLICATIONS OF HEPATITIS C
      CAUSED LIVER CIRRHOSIS.
AB  - Introduction: Model for End-Stage Liver Disease (MELD) is a scoring system used
      to estimate the severity of chronic liver disease. Score is based on objective
      variables and predicts survival among different populations of patients. Study
      Aim. The aim of the study was to retrospectively analyze potential connection
      between MELD score and laboratory findings and complications of hepatitis C
      caused liver cirrhosis. Materials and Methods: A retrospective cross-sectional
      study based on data from Riga East Clinical University Hospital from the time
      period of 2010 to 2014 was performed. Original protocol and database were
      developed with consequential data statistical analysis using IBM SPSS Statistics
      ver.20.0. Results: In total 221 cirrhosis cases were enrolled in the study. 128
      (58%) cases were male and 93 (42%) female. Mean age was 52.7 +/- 13.4 years.
      Statistically significant correlation was found between leukocytes (r = 0.4, p <
      0.001), blood urea (r = 0.4, p < 0.001), serum albumin (r = -0.4, p < 0.001), C
      reactive protein (r = 0.4, p < 0.001) and MELD score. Higher leukocytes, higher
      urea, C-reactive protein and lower serum albumin rates give higher MELD score. At
      the time of hospitalization 208 (94%) of the patients had different complications
      of liver cirrhosis. Correlation between MELD score varied significantly with
      esophageal varices (r = 0.2, p < 0.05) and esophageal vein bleeding (r = 0.2, p <
      0.05). Results show, if patient is present with esophageal varices and esophageal
      vein bleeding, MELD score is higher. Conclusion: Patients with higher leukocytes,
      blood urea nitrogen and lower serum albumin level are presenting higher MELD
      score. In patients who presented with esophageal varices and esophageal vein
      bleeding, higher MELD score was observed.

PMID- 30284417
TI  - [CLINICAL AND MORPHOLOGICAL CHARACTERISTICS OF INTESTINAL LESIONS IN PATIENTS
      WITH PRIMARY SCLEROSING CHOLANGITIS].
AB  - Objective: To compare the clinical, endoscopic picture and morphological changes
      of the intestinal mucosa in patients with primary sclerosing cholangitis (PSC).
      Materials and methods: 31 patients with PSC (women - 15 men - 16) were included
      in study group. The diagnosis of ulcerative colitis (UC) was established in 8
      patients, Crohn's disease (CD) - in 5, unclassified colitis (UCC) - in 7, and 11
      patients had no clinical and endoscopic signs of IBD. The control group consisted
      of 30 patients with IBD: UC - 20 patients, CD - 10 persons. All the patients
      performed ileocolonoscopy (ICS) with multiple biopsy and histological examination
      of material. Results: The prevalence of IBD in patients with PSC was 64.5%. IBD
      with PSC was characterized by extensive colitis with mild clinical activity.
      Morphological activity of IBD associated with PSC was usually moderate and
      severe. Morphological activity of disease in IBD/PSC group was lower than in UC
      alone (p < 0.05). IBD onset came before PSC symptoms (p < 0.05). Distal gradient
      of inflammation in colon predominated in IBD/PSC group when disease starts with
      IBD symptoms, in case of PSC symptoms - proximal gradient was more frequent. In
      IBD/PSC group affected ileum were detected in a third of cases, including CD
      ileitis - 60%, backwash ileitis in UC (NCC) in 26.7%, that was significantly
      frequently than in UC alone (p = 0.02). Within the IBD/PSC group 30% of patients
      with colitis were without damaging of rectum. In all the patients with PSC
      without clinical, endoscopic signs of colitis polymorphocellular infiltration of
      mucosa were founded. Eosinophilic infiltration of mucosa in group of PSC met
      significantly more frequently than in other study groups. Fibrosis of intestinal
      mucosa was founded significantly more frequently in group of PSC without IBD
      compared with UC/PSC and UC patients, but not with CD group. Conclusions: For IBD
      in PSC extensive colitis without lesions of the rectum, backwash ileitis are
      common. There are some morphological differences in the intestinal lesions within
      the IBD/PSC patients depending on the type of disease onset. There is a
      dissociation between low clinical activity and intensive morphological
      inflammation. When PSC had no clinical features of IBD, a microscopic ileocolitis
      (characterized by eosinophilic infiltration and fibrosis of the intestinal
      mucosa) without nosological classification was founded in all patients.

PMID- 30284418
TI  - [ASSESSMENT OF MATRIX METALLOPROTEINASES AND THEIR TISSUE INHIBITORS FOR NON
      INVASIVE DIAGNOSIS OF LIVER FIBROSIS IN PATIENTS WITH NONALCOHOLIC FATTY LIVER
      DISEASE].
AB  - Objective: To evaluate the diagnostic value of MMP-9, TIMP-1 and 2 as non
      invasive markers of liver fibrosis in the NAFLD to improve the management of
      patients with this pathology. Materials and methods: We examined 99 patients with
      NAFLD and different stages of fibrosis, 83 men, 16 women, median age 45 (range 40
      55) years. We assessed of risk factors for liver fibrosis in the NAFLD,
      anthropometric indicators, biochemical analysis of blood, abdominal ultrasonic
      studies, the levels of MMP-9, TIMP-1 and 2. Depending on the stage of fibrosis (0
      4), established as a result of liver elastometry (Fibroscan), patients were
      divided into 5 groups: n = 27, n = 22, n = 23, n = 14, n = 13, respectively.
      Results: Between the groups in medical history, physical examination, calculation
      of BMI and the ratio of waist to hip volume (W/H) no significant differences were
      found. 64,6% of patients had abdominal obesity (BMI - 31,5 (29,1-33,9), W/H -
      1,02 (1,01-1,05). Obesity and abdominal obesity (BMI, W/H) had a significant
      positive relationship of moderate streight (rs = (0,257), p < 0,04, rs = (0,301),
      p < 0,02, respectively), with the stage of liver fibrosis. The groups were
      significant differences in the level of glucose, total bilirubin (p < 0,04, p <
      0,03, respectively). At the time of the examination, 57,5% of patients had
      steatosis, other patients had steatohepatitis. No significant differences in the
      level of liver function tests (ALT, AST) in the study groups were found.
      Significant differences were found in level of TIMP-2 (p < 0,04). TIMP-2 had a
      significant positive correlation with the severity of fibrosis in the hepatic
      tissue (rs = (0,349), p < 0,004). Conclusion: TIMP-2 may be considered as a
      potential non-invasive marker for the diagnosis of liver fibrosis in patients
      with NAFLD.

PMID- 30284419
TI  - [THE IMPACT OF METABOLIC SYNDROME ON THE STRUCTURAL AND FUNCTIONAL STATE OF THE
      LIVER PARENCHYMA].
AB  - The aim of study was to evaluate changes of biochemical, immunological parameters
      and the state of the liver parenchyma in patients with metabolic syndrome. The
      correlation analysis have shown significant connections between serum
      concentration of TIMP-1 and tryglicerid level (p = 0,04) and increase activity of
      GGTP (r = 0,0475). The activity of GGTP correlated with increase of lipoproteids
      of low density in serum (r = 0,034). The intensity of liver tissue changes on
      sonography in accordance with mathematical analysis was 2,31 +/- 0,23 points.

PMID- 30284420
TI  - [CONDITION OF HEPATOBILIARY SYSTEM IN JUVENILE RHEUMATOID ARTHRITIS].
AB  - The Article is dedicated to the results of the clinical-biochemical, biophysical
      and pathomorphological study of liver in the patients with juvenile rheumatoid
      arthritis. Liver injury in 64.8 % of patients with JRA was found, showing signs
      of mesenchymal inflammation, hypoalbuminemia, hyperbilirubinemia, hyperenzymemia.
      The importance of elastography in the early diagnosis of liver fibrosis in
      patients with JRA was determined. Results of morphological studies of patients
      who died of liver JRA treated with methotrexate showed that in contrast to
      patients not receiving methotrexate noted the development of more severe
      disorganized, dystrophic and immunopathological processes with transition to the
      sclerotic and fibromatous changes.

PMID- 30284414
TI  - [Integral approach to the acute exacerbation of chronic obstructive pulmonary
      disease].
AB  - Chronic obstructive pulmonary disease is a set of clinical processes that have in
      common a chronic and progressive obstruction to airflow, with episodes of
      exacerbation. These exacerbations are more frequent and severe over time,
      deteriorating the lung function. The main cause of exacerbations is bacterial
      infection. There are multiple guidelines and documents that statement the
      management of this pathology. However, they focus primarily on the treatment
      during the stable phase. This document addresses the problem of acute
      exacerbation due to an infection from a multidisciplinary perspective, focusing
      on the integral approach to the process, and including etiology, microbiological
      studies, resistance to antimicrobials, risk stratification and initial empirical
      therapeutic management (antibiotic and concomitant). In addition, it includes an
      approach to more complex aspects such as the management of special populations
      (elderly and immunosuppressed) or therapeutic failure. Finally, more
      controversial topics such as prophylaxis of infection or palliative treatment are
      specifically discussed.

PMID- 30284421
TI  - [CHANGES IN LABORATORY MARKERS OF ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH LIVER
      CIRRHOSIS].
AB  - Aim of the research: To study the dynamics of endothelial dysfunction (ED)
      laboratory markers depending on the functional state of the liver in patients
      with severe forms of liver cirrhosis (LC). Materials and methods: 387 patients
      with LC were examined. In order to study the laboratory indexes of ED, levels of
      antitrombin (AT) III, D-dimer, von Willebrand Factor (wWF), endothelin-1 (Et-1)
      were determined. The extent of liver damage was determined using C13-methacetin
      breath test (C13-MBT) and taking into account the results of specially designed
      tests (Forns, FibroIndex, FIB-4, APRI, HALT-C, MDA, GUCI, FPI). Results: Our
      investigations confirm the presence of ED in patients with LC. The analysis of
      the results shows a dependincy between the severity of ED laboratory indexes and
      the level of LC severity: a progressive aggravation of ED indexes in proportion
      to liver damage severity growth. Conclusions: 1. Vessel ED is observed in
      patients with LC, which is manifested in the derangement of its biological
      markers concentration, namely Et-1, vWF, AT III and D-dimer. 2. In patients with
      LC a dependincy between the ED indexes and level of liver damage severity
      according to Child-Pugh was determined, namely the progression of biochemical ED
      markers of blood serum depending on the severity of liver damage according to C13
      MBT results combined with the results of specialy designed tests (Forns,
      FibroIndex, Fib-4, APRI, HALT-C, MDA, GUCI, FPI).

PMID- 30284422
TI  - [GENETIC PREDISPOSITION TO DEVELOPMENT OF TOXIC HEPATITIS].
AB  - Aim: The aim of this study was to investigate the frequency of polymorphic
      variants of genes CYP2E1 and GSTA1 in patients with pathology of the
      hepatobiliary system (PHS) and healthy individuals in the Republic of
      Bashkortostan, as well as an analysis of possible associations of genotypes of
      this gene with the development of PHS. Materials and methods: There were examined
      81 patients with pathology of the hepatobiliary system. Was studied association
      analysis of polymorphic loci of genes CYP2E1 and GSTA1. Results: The study
      demonstrated that a marker of risk of developing the disease is AA genotype (OR =
      2,09; 95% CI 1,07-4,10) polymorphic locus gene rs3957357 GSTA1.

PMID- 30284423
TI  - [THE CLINICAL COURSE OF HEPATITIS C IN CHILDREN WITH DIFFERENT VARIANTS OF THE
      GENE POLYMORPHISM IL28B].
AB  - Aim of investigation: The aim of the research is to study the clinical course of
      hepatitis C in children with different variants of the gene polymorphism of IL
      28B. Materials and methods: We observed 94 children (46 girls and 48 boys) with
      chronic hepatitis C (CHC) in age from 3 to 17 years (mean age 10 years). There
      were significant differences in the distribution of allele frequencies in
      children with chronic hepatitis C and in the population. In children with chronic
      hepatitis C significantly increased the incidence of the T allele at the locus of
      the gene IL-28B rs12979860 C>T, which makes it possible to consider it as a
      predictor of antiviral therapy ineffective. Results: When analyzing the frequency
      of occurrence of a polymorphic variant T>G [rs8099917] IL-28B gene in children
      with chronic hepatitis C and healthy children revealed no differences in the
      distribution of alleles. Conclusion: Personalized approach to the appointment of
      HCV antiviral therapy in children is to carry out genetic studies to determine on
      the basis of predictive features of the course of HCV in children during the
      treatment.

PMID- 30284424
TI  - [THE RHYTHMIC ORGANIZATION OF THE ANNUAL DYNAMICS OF FUNCTIONAL INDICATORS OF RAT
      LIVER UNDER TOXIC LOAD].
AB  - Purpose: The purpose of this study was to investigate the annual dynamics of the
      functional state of the liver of rats with experimental hepatitis on early period
      of intoxication. Materials and methods: This research was conducted for three
      years on 172 adult male rats Wistar. The toxic hepatitis was caused by
      subcutaneous injection three times a 50% oil solution of carbon tetrachloride.
      The studies were conducted in the winter (January), summer (June-July), spring
      (April) and autumn (October) on the 4th day after the last administration of the
      toxin. Activity of alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST), the level of total lipids (TL), total bilirubin (TB), malondialdehyde
      (MDA) and thymol (T) using standard sets of Biotest "Lachema" were determined in
      the blood serum. Statistic processing of primary chronograms of investigated
      parameters was performed with the program "sosinor analysis." Results: It was
      found that in the control animals was dominated by annual and circannual rhythms
      of the liver functions and in the spectra of the studied parameters were observed
      several subdominant harmonic. The maxima of liver function detected to the
      different time intervals on an annual scale, that is, they were not coordinated
      with each other. On day 4 experimental hepatitis was increased the average annual
      of study functions (with the exception of TL) and in their rhythmic organization
      was observed the inner synchronization by period and acrophase. In the spectra of
      the rhythms of the studied parameters mainly was determined by only the annual
      harmonic with acrophase in the autumn months. It can together indicate the
      development of a powerful pathological process in the liver.

PMID- 30284425
TI  - [NERVOUS REGULATION OF BILIARY TRACT MOTILITY].
AB  - Aim: The study of mechanisms of regulation of biliary tract motility by divisions
      of autonomic nervous system (ANS). Material and methods: Experiments were carried
      out on rabbits, chinchillas weighing 3.5-4 kg using gentle methods of treatment
      of experimental animals. Electromotor activity of electromotor (EMA) of the
      gallbladder and sphincter of Oddi was recorded. Irritation of the nerve produces
      an electrical pulse duration of 2 ms, the amplitude of 1.5-15 V, frequency of 10
      Hz. Results: The mechanism of vagal inhibition of sphincter of Oddi motility and
      unidirectional stimulatory influence of ANS divisions on the motility of the
      gallbladder and sphincter of Oddi was studied. It was established that in the
      mechanism of vagal inhibition of sphincter of Oddi motility involved intramural
      adrenergic neurons synaptically connected with preganglionic parasympathetic
      fibers. At the stimulatory effect of vagus on biliary tract motility serotonergic
      intramural neurons are involved transmitting excitation to serotonin receptors of
      effector tissue.

PMID- 30284427
TI  - [PREVENTION OF BLEEDING FROM ESOPHAGEAL VARICES IN CIRRHOSIS].
AB  - Aim: The aim was to improved results of treatment of patients with threatened or
      held bleeding from esophageal varices on the background of liver cirrhosis.
      Materials and Methods: The analysis of the survey results and endoscopic
      treatment of 40 patients with liver cirrhosis complicated by threatened or held
      bleeding from esophageal varices. The effectiveness of the treatment was assessed
      by the dynamics of recourse degree esophageal varices, presence and character of
      postoperative complications and mortality. Results: Application of endoscopic
      ligation as primary and secondary prevention of bleeding from esophageal varices
      can improve the immediate and long-term results of treatment of patients with
      liver cirrhosis complicated by portal hypertension. Prevention of bleeding from
      esophageal varices is a dynamic endomonitoringe supplemented with repeated
      courses of endoscopic ligation.

PMID- 30284426
TI  - [DIFFERENTIAL MANAGEMENT AT THE SPHINCTER OF ODDI DYSFUNCTION AFTER
      CHOLECYSTECTOMY].
AB  - Aim: Develop a differential management at the patients with suspected sphincter
      of Oddi dysfunction after cholecystectomy. Materials and methods: 169 patients
      after cholecystectomy, divided into 2 groups. 1st group - 60 patients after
      repeated surgery formed as a comparison group. They multivariate analysis of
      clinical, laboratory and ultrasonic data revealed the most significant signs of
      organic causes of cholestasis, expressed in scores. 2nd group - 109 patients with
      a suspected sphincter of Oddi dysfunction, who did not have symptoms of organic
      pathology. Types of bile outflow were assessed by hepatobiliary scintigraphy
      (GBSG). In cases of doubtful diagnoses computer tomography, magnetic resonance
      cholangiopancreatography, and/or retrograde cholangiopancreatography are
      performed. Results: According to the scoring system, patients 1st group scored 4
      or more (8,7 +/- 3,87) points. GBSG performed only in 7 (11.6%) patients, and in
      all cases the cholestatic type of bile outflow was detected. The amount of
      estimated points in the 2nd group was 2-3 points (2,43 +/- 0,34; p < 0.05). GBSG
      performed in all patients and three types of bile outflow were revealed: normal -
      in 21 (19.2%) patients, cholestatic in 8 (7.3%), and accelerated - in 80 (73.3%)
      patients. When refining the diagnosis in 10 (9%) patients had hidden organic
      disorders of bile outflow, served as an indication for surgery. Conclusion:
      Scoring system for the assessment of the suspected sphincter of Oddi dysfunction
      allows to differentiate of patients for invasive research and surgery. In our
      study group of 109 patients received less than 4 points, they have dominated the
      functional disorders, but the results of a detailed examination, 9% of patients
      had latent organic changes that have become indications for surgical treatment.

PMID- 30284428
TI  - ?
AB  - Aim: To study and compare the results of reconstructive and restoretive
      operations for strictures and bile duct injuries in patients operated by
      traditional methods and with the use of microsurgical techniques. Materials and
      methods: analysis of 181 and reconstructive restore operations reconstruction
      works produced on the occasion of strictures (111) and intraoperational damage
      (16) of the bile ducts, strictures choledocho-duodenal anastomosis and
      choledochocele (20), congenital cysts of the bile ducts (10), chronic indurative
      pancreatitis (15), the Fatherof papilla stenosis (5), syndrome Mirizzi 4 types
      (4). In the formation biliodigestive anastomoses traditional technique applied in
      116 patients, microsurgical by 65. Results: a comparative evaluation of results
      of surgical treatment of patients operated on traditional way and with the use of
      microsurgery technique showed a reduction in the number of postoperative
      complications in patients undergoing microsurgical operations, such as the
      insolvency of the seams biliodigestive anastomosis, hepatic failure, acute
      cholangitis, stricture of the biliodigestive anastomosis. Conclusion: to improve
      the results of reconstructive operations on the extrahepatic bile ducts
      contributes microsurgical techniks, which provides minimal trauma to the tissues,
      histologically accurate adaptation of homogeneous layers sew bodies, contributes
      healing of biliodigestive anastomosis primary tension. In the absence of
      conditions for the imposition of microsurgical bilitigating anastomosis without
      frame drainage should prima adopt changeable transhepatic drainage as in
      reconstructive and restorative operations.

PMID- 30284429
TI  - [FUNCTIONAL AND CLINICAL DISORDERS OF THE LUNG IN PATIENTS WITH CIRRHOSIS AND
      THEIR DYNAMICS IN OPERATIONS TUNNELING LIVER].
AB  - Aim: Aim. To evaluate lung function in patients with liver cirrhosis of the liver
      with conservative therapy and surgery tunneling liver. Materials and methods: The
      study involved 55 patients with liver cirrhosis with portal hypertension.
      Patients were randomized into 2 groups. In the first group (n = 40) patients
      received medication. Patients of the second group (n = 15) was performed
      tunneling liver shunt operation. Results: In patients with liver cirrhosis
      observed clinical and functional remodeling of the lung appears shortness of
      breath, coughing, wheezing, and restrictive ventilatory disorders. Conclusions:
      In patients with cirrhosis of the liver after tunneling is observed normalization
      of lung ventilation. After conservative treatment reliable normalization of lung
      function occurs.

PMID- 30284430
TI  - [MALABSORPTION FAT-SOLUBLE VITAMINS AND PROSPECTS OF THEIR USE IN LIVER
      DISEASES].
AB  - In a review article considers issues of efficiency and tactics of the purpose of
      fat-soluble vitamins, as in cholestatic and noncholestatic liver disease, as well
      as water-soluble vitamins, particularly vitamin C cholelithiasis. Oxidative
      stress due to chronic inflammation is one of the major conversion mechanisms of
      liver fibrosis in cirrhosis. The imbalance between production of reactive oxygen
      species and antioxidant defense causes a number of pathophysiological changes in
      the liver, including activation of hepatic stellate cells. The carriers of the
      I148M PNPLA3 mutation was not observed concentration reduction in liver vitamin A
      with increasing severity of the disease, but the observed decrease in the level
      of circulating retinyl palmitate and retinol-binding protein. To the appointment
      of vitamin A in liver disease should be approached with caution. Hypervitaminosis
      A leads to accelerated liver fibrosis and stimulates carcinogenesis. Currently
      actively studied the possibility of using vitamin E as an antioxidant, in
      patients with non-alcoholic fatty liver disease. His presence in the membranes
      phospholipid bilayer allows cells to prevent non-enzymatic oxidation of cell
      components by free radicals. Vitamin E can suppress the profibrotic processes. In
      patients with chronic cholestatic liver disease is common, vitamin K deficiency,
      even when administered, and is associated with the degree of cholestasis and
      severity of disease. The vitamin D deficiency, liver disease is also associated
      with the severity of disease correlated with the severity of liver failure and
      infectious complications. Vitamin D is an independent prognostic parameter for
      mortality risk in patients with liver cirrhosis.

PMID- 30284431
TI  - [ANALYSIS OF THE EFFECTIVENESS OF DIFFERENT METHODS OF HEMOSTASIS AND PREVENTION
      OF BLEEDING IN PORTAL HYPERTENSION].
AB  - The review presents the whole range of modern methods of hemostasis and
      prevention of bleeding in patients with portal hypertension, assessed the
      effectiveness of each.

PMID- 30284432
TI  - [METABOLIC CORRECTOR WITH HEPATOPROTECTIVE PROPERTIES RUNIHOL(r): FROM SCREENING
      TO CLINICAL TESTING].

PMID- 30284433
TI  - [COMPARATIVE EXPERIMENTAL EVALUATION OF THE EFFECTIVENESS OF MODERN PROBIOTICS,
      PREBIOTICS, SYNBIOTICS AND METABIOTICS FOR CORRECTION OF INTESTINAL
      MICROBIOCENOSIS IN ANIMALS WITH ANTIBIOTIC-ASSOCIATED DYSBIOSIS].
AB  - Probiotics for decades were leading in the arsenal of tools for correction of
      intestinal microbiocenosis. However, the response of representatives of
      intestinal microbiota to enteral intake of probiotics is variable, and in some
      individuals may be missing. Despite the fact that scientists still disagree on
      the necessity of forced settlement of normal microbiota at intestinal dysbiosis,
      large number of medicinal products, functional foods, dietary supplements, which
      efficiency is not always straightforward, is available for sale. The results of
      comparative experimental study of the effectiveness of 18 modern preparations for
      correction of intestinal microbiocenosis at antibiotic-associated dysbiosis in
      animals are presented. Conclusion is done on the need to evaluate efficacy and
      safety of tools developed for intestinal microbiota correction in animal
      experiments, followed by confirmation of clinical trials.

PMID- 30284434
TI  - [STAGING SYSTEMS OF HEPATOCELLULAR CARCINOMA].
AB  - It is the data of literature on existing classifications and systems of
      assessment and prognosis of hepatocellular carcinoma (HCC). In some
      classifications takes into account only the characteristics of the tumor tissue,
      in others are used biochemical and clinical characteristics in addition. Some
      systems allow to predict the survival of patients regardless of the stage of the
      disease, while others are most effective for the individual stages. The
      international TNM classification is generally accepted for the development of
      treatment methods and determining the forecast mainly for resectable HCC forms.
      The Japanese staging system (JIS) is mainly recommended for operable patients.
      Italian scale (CLIP), on the contrary, is intended to analyze HCC, which is not
      subject to surgical treatment. The Barcelona classification of liver cancer
      (BCLC) is considered the most universal, because it takes into account the stage
      of disease, the condition of the liver parenchyma and does not depend on the
      method of treatment and the patient's place of residence. Therefore, the choice
      of staging system and assessment of disease prognosis should be based on the
      clinical and morphological features of the disease, taking into account features
      of application of various scales.

PMID- 30284435
TI  - [HEREDITARY HEMOCHROMATOSIS (clinical observations)].
AB  - The article presents two clinical observations of patients with different course
      genetically verified primary hemochromatosis.

PMID- 30284436
TI  - [ASYMPTOMATIC INTRAHEPATIC CHOLANGIOCARCINOMA].
AB  - Objective: To analyze the cases of intrahepatic cholangiocarcinoma posthumous
      diagnosis in patients with concomitant atherosclerotic lesions of the femoral
      arteries. Key points: The present report describes the clinical observation of a
      rare tumor - intrahepatic cholangiocarcinoma. Difficulties of its early diagnosis
      is a combination of symptoms of tumor progression with pain in the lumbar spine,
      the latter in the presence of concomitant femoral arteries of atherosclerotic
      lesions, characterized by pain similar localization has led to delay cancer
      research. Conclusion: Upgrading differential diagnostic procedures with a
      combination of pain in the lumbar spine with symptoms of tumor progression
      through the use of a computer and / or positron emission tomography study of
      plasma levels onkomarkera CA-19-9, magnetic resonance contrast
      holangiopankreatikografii, would in this clinical case in a timely manner to make
      the correct diagnosis.

PMID- 30284437
TI  - Evaluation of Estrogenic Activity of Novel Bisphenol A Alternatives, Four
      Bioinspired Bisguaiacol F Specimens, by in Vitro Assays.
AB  - Alternatives to bisphenol A (BPA), such as lignin-inspired bisguaiacol F (BGF),
      are of interest for food contact materials due to increasing evidence of
      estrogenic activity (EA) and exposure-correlated harmful effects of BPA and its
      analogues. BGF has similar thermal and mechanical properties to BPA, but contains
      additional methoxy substituents that may significantly reduce its endocrine
      disruption potential. In this study, the EA of four BGF samples with different
      regioisomer ratios was quantified relative to 17beta-estradiol at ten
      concentrations by using two in vitro assays: MCF-7 cell proliferation and
      VM7Luc4E2 transactivation (TA). The results suggest BGF mixtures with higher
      molar ratios of p, p'-BGF and o, p'-BGF regioisomers exhibited lower EA than BPA,
      while BGF samples containing higher molar ratios of m, p'-BGF had no detectable
      EA over a wide range of test concentrations. These findings suggest the potential
      of BGF as a viable alternative to BPA for use in more environmentally friendly
      materials.

PMID- 30284438
TI  - Formation of Icephobic Surface with Micron-Scaled Hydrophobic Heterogeneity on
      Polyurethane Aerospace Coating.
AB  - Development of an anti-icing surface on a desired industrial coating patch/object
      has been the persistent challenge to several industries, such as aviation and
      wind power. For this aim, performing surface modification to implement the
      icephobic property on existing commercial coatings is important for practical
      applications. This work accomplishes an icephobic coating overlying a PPG
      aerospace polyurethane coating. It manifests a clear capability to delay the
      formation of frost as well as to reduce the adhesion strength of ice. This
      icephobic coating is sustained by a unique hydrophobic heterogeneity in the
      micron-scale of segregation, which is realized through solution casting of a
      specific copolymer consisting of random rigid and soft segments, namely
      poly(methyl methacrylate) and poly(lauryl methacrylate-2-hydroxy-3-(1-amino
      dodecyl)propyl methacrylate), respectively. A wrinkled pattern developed over the
      coating is observed because of the diverse traits between these two segments.
      Besides, the OH/NH groups of the soft segment are crosslinked by a diisocyanate
      monomer upon drying and curing to strengthen the coating. More importantly,
      integration of a small dose of paraffin wax into the copolymer induces a spread
      of soft microdomains on the winkled pattern surface. It is hypothesized that
      these dual heterogeneous assemblies are responsible for the icephobicity since
      they instigate distinct interactions with condensed water droplets. Lastly, the
      thermoelectric cooling (Peltier effect) and the adhesion strength of ice on the
      typical coatings were assessed. This investigation also includes examination on
      the icephobic durability of coating, which is enhanced when a small amount of
      polyethylene oligomer is incorporated into the coating.

PMID- 30284439
TI  - Application of C-Terminal 7-Azabicyclo[2.2.1]heptane to Stabilize beta-Strand
      like Extended Conformation of a Neighboring alpha-Amino Acid.
AB  - beta-Strands are formed by extended linear peptide chains that are usually paired
      to form beta-sheet structure through interstrand hydrogen bonding. Linking a
      structured organic molecule with alpha-amino acid(s) can enforce or stabilize
      beta-strand-like extended structures of the jointed amino acids. Spectroscopic
      and simulation studies indicated that the presence of a C-terminal 7
      azabicyclo[2.2.1]heptane amine (Abh) favors a beta-strand-like extended
      conformation of the adjacent alpha-amino acid on the N side. The bridgehead
      substitution of the Abh unit biases the amide cis-trans equilibrium of the
      adjacent alpha-amino acid residue to cis conformation. The proximity, specified
      by the presence of bond paths (such as H-H bond path) between the bridgehead
      proton of Abh and the alpha-proton of the alpha-amino acid provides a driving
      force favoring the extended conformation, which is independent of solvents. These
      results provide a basis for de novo design of beta-strand-mimicking extended
      peptides by using beta-strand enforcer/stabilizer even in the absence of the
      interstrand hydrogen bonding.

PMID- 30284440
TI  - Acid-Interface Engineering of Carbon Nanotube/Elastomers with Enhanced
      Sensitivity for Stretchable Strain Sensors.
AB  - Stretchable strain sensors with high sensitivity or gauge factor (GF), large
      stretchability, and long-term durability are highly demanded in human motion
      detection, artificial intelligence, and electronic skins. Nevertheless, to
      develop high-sensitive sensors without sacrificing the stretchability cannot be
      realized using simple device configurations. In this work, an acid-interface
      engineering (AIE) method was proposed to develop a stretchable strain sensor with
      high GF and large stretchability. The AIE generates a layer of SiO x at the
      interface between the carbon nanotube (CNT) film and Ecoflex, playing a key role
      in enhancing the sensor's GF. Compared to devices without AIE (GF = 2.4), the
      ones with AIE are significantly improved. At an AIE time of 10 min, the GF up to
      1665.9 is achieved without sacrificing the stretchability (>100%). The AIE
      generated cracks are found to modulate the electrical behaviors and enhance the
      GFs of sensors with AIE through the crack-induced rapid reduction in the
      electrical conduction pathway, which is manipulated by the CNTs bridging over the
      cracks. The device with AIE proves its high mechanical durability through a
      cycling test (>10 000 cycles) at a high strain up to ~80%, further paving its
      practical applications in various human motion detections.

PMID- 30284441
TI  - Binding and Precipitation of Germanium(IV) by Penta- O-galloyl-beta-d-glucose.
AB  - Complex formation and precipitation of germanium by a well-characterized
      hydrolyzable tannin, 1,2,3,4,6-penta- O-galloyl-beta-d-glucose (PGG), was studied
      in this work. Two simple phenolic compounds, methyl gallate and gallic acid, were
      also used for comparison purposes. The influence of pH on the stoichiometry and
      conditional association constants (log K) of the germanium complexes was
      investigated. UV-visible spectroscopy showed the successive formation of GePGG
      and Ge2PGG at pH 6.0 and of GePGG at pH 4.0. The results of the precipitation
      experiments indicated that germanium precipitation was influenced by organic
      solvents, pH values, the germanium/PGG ratio, and the presence of zinc. Acetone
      had the biggest effect on the solubility of these complexes, and lower pH values
      favored the precipitation of the complex. The results showed that a germanium/PGG
      ratio of more than 3:1 was essential for precipitation. Furthermore, the presence
      of zinc ions in the solution decreased the precipitation.

PMID- 30284442
TI  - High Thermoelectric Performance Originating from the Grooved Bands in the ZrSe3
      Monolayer.
AB  - Low-dimensional layered materials have attracted tremendous attentions because of
      their wide range of physical and chemical properties and potential applications
      in electronic devices. Using first-principles method taking into account the
      quasi-particle self-energy correction and Boltzmann transport theory, the
      electronic transport properties of the ZrSe3 monolayer are investigated, where
      the carrier relaxation time is accurately calculated within the framework of
      electron-phonon coupling. It is demonstrated that the high power factor of the
      monolayer can be attributed to the grooved bands near the conduction band
      minimum. Combined with the low lattice thermal conductivity obtained by solving
      the phonon Boltzmann transport equation, a considerable n-type ZT value of ~2.4
      can be achieved at 800 K in the ZrSe3 monolayer.

PMID- 30284443
TI  - Flexible Electronic Synapses for Face Recognition Application with Multimodulated
      Conductance States.
AB  - An artificial synaptic device with a continuous weight modulation behavior is
      fundamental to the hardware implementation of the bioinspired neuromorphic
      systems. Recent reported synaptic devices have a less number of conductance
      states, which is not beneficial for the continuous modulation of weights in
      neuromorphic computing. Preparing a device with as many conductance states as
      possible is of great significance to the development of brain-inspired
      neuromorphic computing. Here, we present a two-terminal flexible organic synaptic
      device with ultra-multimodulated conductance states, realizing a face recognition
      functionality with a strong error-tolerant nature for the first time. The device
      shows an excellent long-term potentiation or long-term depression behavior and
      reliability after 1000 folded destructive tests. There are 600 continuous ultra
      multimodulated conductance states, which can be used to realize the great face
      recognition capability. The recognition rates were 95.2% and above 90% for the
      initial and 15% noise pixel images, respectively. The strong error-tolerant
      nature indicates a potential application of a flexible organic artificial
      synaptic device with ultra-multimodulated conductance states in the large-scale
      neuromorphic systems.

PMID- 30284445
TI  - Sequential Michael Addition/Electrophilic Alkynylation: Synthesis of alpha
      Alkynyl-beta-Substituted Ketones and Chromanones.
AB  - We describe the synthesis of alpha-alkynyl-beta-substituted cyclic ketones and
      analogue chromanones via one-pot Michael addition/hypervalent iodine-based alpha
      alkynylation. Cu(I)-catalyzed Michael addition using either alkyl-aluminum or
      Grignard reagents, followed by diastereoselective electrophilic alkynylation of
      the resulting enolate by 1-ethynyl-1lambda3,2-benziodoxol-3(1H)-one (EBX)
      resulted in the alpha-alkynyl-beta-substituted cyclic ketones or chromanones
      within 34-89% yield (16 examples). The reaction was successfully upscaled to the
      5 mmol scale, and further functionalization of a model alkynylated ketone was
      demonstrated.

PMID- 30284444
TI  - Lesion Sensing during Initial Binding by Yeast XPC/Rad4: Toward Predicting
      Resistance to Nucleotide Excision Repair.
AB  - Nucleotide excision repair (NER) excises a variety of environmentally derived DNA
      lesions. However, NER efficiencies for structurally different DNA lesions can
      vary by orders of magnitude; yet the origin of this variance is poorly
      understood. Our goal is to develop computational strategies that predict and
      identify the most hazardous, repair-resistant lesions from the plethora of such
      adducts. In the present work, we are focusing on lesion recognition by the
      xeroderma pigmentosum C protein complex (XPC), the first and required step for
      the subsequent assembly of factors needed to produce successful NER. We have
      performed molecular dynamics simulations to characterize the initial binding of
      Rad4, the yeast orthologue of human XPC, to a library of 10 different lesion
      containing DNA duplexes derived from environmental carcinogens. These vary in
      lesion chemical structures and conformations in duplex DNA and exhibit a wide
      range of relative NER efficiencies from repair resistant to highly susceptible.
      We have determined a promising set of structural descriptors that characterize
      initial binding of Rad4 to lesions that are resistant to NER. Key initial binding
      requirements for successful recognition are absent in the repair-resistant cases:
      There is little or no duplex unwinding, very limited interaction between the beta
      hairpin domain 2 of Rad4 and the minor groove of the lesion-containing duplex,
      and no conformational capture of a base on the lesion partner strand. By
      contrast, these key binding features are present to different degrees in NER
      susceptible lesions and correlate to their relative NER efficiencies.
      Furthermore, we have gained molecular understanding of Rad4 initial binding as
      determined by the lesion structures in duplex DNA and how the initial binding
      relates to the repair efficiencies. The development of a computational strategy
      for identifying NER-resistant lesions is grounded in this molecular understanding
      of the lesion recognition mechanism.

PMID- 30284446
TI  - Characterization of Interactions and Phospholipid Transfer between Substrate
      Binding Proteins of the OmpC-Mla System.
AB  - The outer membrane (OM) of Gram-negative bacteria is a permeability barrier that
      impedes the entry of external insults, such as antibiotics and bile salts. This
      barrier function depends critically on the asymmetric lipid distribution across
      the bilayer, with lipopolysaccharides (LPS) facing outside and phospholipids
      (PLs) facing inside. In Escherichia coli, the OmpC-Mla system is believed to
      maintain OM lipid asymmetry by removing surface exposed PLs and shuttling them
      back to the inner membrane (IM). How proteins in the pathway interact to mediate
      PL transport across the periplasm is not known. Evidence for direct transfer of
      PLs between these proteins is also lacking. In this study, we mapped the
      interaction surfaces between the two PL-binding proteins, MlaC and MlaD, using
      site-specific in vivo photo-cross-linking, and obtained a physical picture for
      how these proteins may transfer PLs. Furthermore, we demonstrated using purified
      proteins that MlaD spontaneously transfers PLs to MlaC, suggesting that the
      latter has a higher affinity for PLs. Our work provides insights into the
      mechanism of bacterial intermembrane lipid transport important for the
      maintenance of OM lipid asymmetry.

PMID- 30284447
TI  - Toxicity and Toxicokinetics of Amygdalin in Maesil ( Prunus mume) Syrup:
      Protective Effect of Maesil against Amygdalin Toxicity.
AB  - Maesil ( Prunus mume, green plum)-based products have been widely used in Asian
      cooking, which may contain amygdalin enzymatically converted to hydrogen cyanide
      after oral ingestion. In this study, the toxicity of Maesil syrups matured with
      and without Maesils was evaluated by focusing on relationship between amygdalin
      toxicity and its metabolic change. The cytotoxicity of amygdalin was highly
      related to its metabolites converted by beta-glucosidase, and the metabolic
      change was retarded in Maesil syrup. Toxicokinetics revealed extremely low oral
      absorption and short half-life of amygdalin standard and Maesil syrups, and
      delayed metabolic change of amygdalin in Maesil syrup was found. It seems that
      complex Maesil syrup components play roles against amygdalin degradation. Maesil
      syrup matured with Maesils had higher total polyphenols, lower amygdalin, and
      shorter half-life in bloodstream than Maesil syrup without Maesils, suggesting
      more safety benefit. No significant oral toxicity of Maesil syrups was found
      after 14-day repeated administration, implying their safety.

PMID- 30284448
TI  - Sequential Fractionation Strategy Identifies Three Missing Proteins in the
      Mitochondrial Proteome of Commonly Used Cell Lines.
AB  - Mitochondria are undeniably the cell powerhouse, directly affecting cell survival
      and fate. Growing evidence suggest that mitochondrial protein repertoire affects
      metabolic activity and plays an important role in determining cell
      proliferation/differentiation or quiescence shift. Consequently, the bioenergetic
      status of a cell is associated with the quality and abundance of the
      mitochondrial populations and proteomes. Mitochondrial morphology changes in the
      development of different cellular functions associated with metabolic switches.
      It is therefore reasonable to speculate that different cell lines do contain
      different mitochondrial-associated proteins, and the investigation of these pools
      may well represent a source for mining missing proteins (MPs). A very effective
      approach to increase the number of IDs through mass spectrometry consists of
      reducing the complexity of the biological samples by fractionation. The present
      study aims at investigating the mitochondrial proteome of five phenotypically
      different cell lines, possibly expressing some of the MPs, through an enrichment
      fractionation approach at the organelle and protein level. We demonstrate a
      substantial increase in the proteome coverage, which, in turn, increases the
      likelihood of detecting low abundant proteins, often falling in the category of
      MPs, and resulting, for the present study, in the identification of METTL12,
      FAM163A, and RGS13. All MS data have been deposited to the MassIVE data
      repository ( https://massive.ucsd.edu ) with the data set identifier MSV000082409
      and PXD010446.

PMID- 30284449
TI  - Total Synthesis and Biological Evaluation of 19-Hydroxysarmentogenin-3 -O-alpha-l
      rhamnoside, Trewianin, and Their Aglycons.
AB  - Cardenolides comprise an important family of natural steroids with a wide
      spectrum of biological activities. Although 19-hydroxysarmentogenin-3- O-alpha-l
      rhamnoside (1a) and trewianin (1b) were structurally determined to have
      cardenolide structures, their biological activities have not been evaluated. The
      6/6/6/5-membered ABCD-ring systems of both 1a and 1b are decorated by a beta
      oriented C17-butenolide, three C11,14,19-hydroxy groups, and a C3-O-l-rhamnoside
      moiety. On the other hand, 1a and 1b are epimeric at the C5-position. The
      structures of 1a and 1b were assembled from four simple fragments by applying a
      convergent and unified strategy. The AB-ring 10a/b and the D-ring 8/9 were
      tentatively tethered at the acetal moiety, and a subsequent stereoselective 6-
      exo radical reaction linked the two fragments. Next, an aldol reaction enabled
      simultaneous introduction of three new stereocenters of the C-rings of 5aa and
      54. Attachment of the C17-butenolide led to aglycons 2a and 2b. l-Rhamnose was
      then installed into 2a and 2b to yield the targets 1a and 1b, respectively.
      Finally, the growth inhibitory activity of 1a, 1b, 2a, and 2b was assessed
      against MCF-7 human breast carcinoma cells. The significantly higher activities
      of 1a and 1b in comparison to 2a and 2b demonstrated the biological importance of
      the monosaccharide substructure.

PMID- 30284450
TI  - Flexible Laser-Induced Graphene for Nitrogen Sensing in Soil.
AB  - Flexible graphene electronics are rapidly gaining interest, but their widespread
      implementation has been impeded by challenges with ink preparation, ink printing,
      and postprint annealing processes. Laser-induced graphene (LIG) promises a facile
      alternative by creating flexible graphene electronics on polyimide substrates
      through the one-step laser writing fabrication method. Herein, we demonstrate the
      use of LIG, created with a low-cost UV laser, for electrochemical ion-selective
      sensing of plant-available nitrogen (i.e., both ammonium and nitrate ions: NH4+
      and NO3-) in soil samples. The laser used to create the LIG was operated at
      distinct pulse widths (10, 20, 30, 40, and 50 ms) to maximize the LIG
      electrochemical reactivity. Results illustrated that a laser pulse width of 20 ms
      led to a high percentage of sp2 carbon (77%) and optimal peak oxidation current
      of 120 MUA during cyclic voltammetry of ferro/ferricyanide. Therefore, LIG
      electrodes created with a 20 ms pulse width were consequently functionalized with
      distinct ionophores specific to NH4+ (nonactin) or NO3- (tridodecylmethylammonium
      nitrate) within poly(vinyl chloride)-based membranes to create distinct solid
      contact ion-selective electrodes (SC-ISEs) for NH4+ and NO3- ion sensing,
      respectively. The LIG SC-ISEs displayed near Nernstian sensitivities of 51.7 +/-
      7.8 mV/dec (NH4+) and -54.8 +/- 2.5 mV/dec (NO3-), detection limits of 28.2 +/-
      25.0 MUM (NH4+) and 20.6 +/- 14.8 MUM (NO3-), low long-term drift of 0.93 mV/h
      (NH4+ sensors) and -5.3 MUV/h (NO3- sensors), and linear sensing ranges of 10-5
      10-1 M for both sensors. Moreover, soil slurry sensing was performed, and
      recovery percentages of 96% and 95% were obtained for added NH4+ and NO3-,
      respectively. These results, combined with a facile fabrication that does not
      require metallic nanoparticle decoration, make these LIG electrochemical sensors
      appealing for a wide range of in-field or point-of-service applications for soil
      health management.

PMID- 30284451
TI  - The girl with the eyeball tattoo-what the ophthalmologist may expect? Case report
      and a review of literature.
AB  - INTRODUCTION: We report a case of patient who underwent bilateral eyeball tattoo
      procedure for cosmetic purpose complicated with intraocular dye injection which
      led to ocular inflammation, secondary glaucoma, and cataract. CASE DESCRIPTION: A
      21-year-old female presented to emergency department with severe right eye pain
      and photophobia 21 days after conjunctival tattooing procedure. Slit-lamp
      examination revealed right-sided eyelid edema and black deposits of tattoo ink
      under the bulbar conjunctiva. Dye deposits were also present in anterior chamber,
      covering corneal endothelium, iris and anterior lens' capsule. Ocular
      inflammation and secondary glaucoma were diagnosed. The patient underwent
      surgical treatment to control ocular inflammation. Intraocular pressure remained
      stable after Nd:YAG iridotomy and on topical drugs. Moreover, during the follow
      up, in contralateral eye, we observed "conjunctival lumps"-local hypersensitivity
      reaction to the dye, which were asymptomatic to the patient. CONCLUSION: Eyeball
      tattooing complications are new challenges that ophthalmologist may have to face
      nowadays. We also reviewed for the first time possible complications of eyeball
      tattooing described in available literature.

PMID- 30284452
TI  - Vitrectorhexis in penetrating eye injuries in adults.
AB  - INTRODUCTION: Vitrectorhexis is an alternative for manual continuous curvilinear
      capsulorhexis originally developed for paediatric cataract surgery. The aim of
      our study was the evaluation of the technique in adult patients with penetrating
      ocular injury and traumatic cataracts. METHODS: Eight eyes of 8 patients (23-41
      years, all males) had penetrating mechanical corneal trauma. Anterior lens
      capsule was penetrated in all cases and additional posterior capsule defect in
      five cases. Intraocular foreign body was detected in one case in the crystalline
      lens and in two cases in the posterior segment. Standard 23G infusion cannula and
      vitreous cutter were applied to perform anterior capsule opening, removal of lens
      material, anterior vitrectomy and pars plana vitrectomy if needed. No
      phacoemulsification or irrigation/aspiration probe was used. RESULTS:
      Vitrectorhexis could be performed in 7 out of 8 cases with the preservation of
      peripheral anterior capsule; primary implantation of posterior chamber
      intraocular lens was possible in all cases (in the bag in three eyes and into the
      sulcus in five eyes). Anterior chamber was stable in all cases intraoperatively,
      and no dropped nucleus or lens fragment loss was observed. Surgery was combined
      with pars plana vitrectomy in three cases, with foreign body removal (when
      necessary). No postoperative complication occurred. CONCLUSION: Vitrectorhexis
      was found to be an effective and safe alternative method in the management of
      complex anterior segment trauma cases. With its use, traditional cataract
      surgical devices can be substituted and additional benefits of vitreous cutter
      can be utilized in selected cases, especially in young adults.

PMID- 30284453
TI  - Evaluation of static and dynamic pupil characteristics in hyperopic anisometropic
      amblyopia.
AB  - PURPOSE: The aim of this study is to perform a comparison of static and dynamic
      pupillometry measurements in patients with hyperopic anisometropic amblyopia and
      age-matched controls. METHODS: This prospective cross-sectional study consisted
      of 38 patients with hyperopic anisometropic amblyopia and 80 control subjects. A
      quantitative pupillometry system was used to evaluate the pupil characteristics
      of higher hyperopic eyes (Group 1), the fellow eyes (Group 2), and healthy eyes
      (Group 3). Static pupillometry measurements were taken including scotopic pupil
      diameter, mesopic pupil diameter, low-photopic pupil diameter, and high-photopic
      pupil diameter. Subsequently, dynamic pupillometry measurements were taken
      including resting diameter, amplitude of pupil contraction, latency of pupil
      contraction, duration of pupil contraction, velocity of pupil contraction,
      latency of pupil dilation, duration of pupil dilation, and velocity of pupil
      dilation. RESULTS: Groups 1 and 2 had statistically significantly lower scotopic
      and high-photopic pupil diameter values compared with Group 3 (p < 0.05). The
      amplitude of pupil contraction values were also statistically significantly lower
      in Groups 1 and 2 compared with Group 3 (p = 0.001 and p = 0.003). However, there
      were no significant differences between the study and the control eyes with
      respect to mesopic and high-photopic pupil diameter, resting diameter, latency of
      pupil contraction, duration of pupil contraction, velocity of pupil contraction,
      latency of pupil dilation, duration of pupil dilation, and velocity of pupil
      dilation values (p > 0.05, for all). CONCLUSION: Static and dynamic pupil
      characteristics of higher hyperopic eyes and their fellow eyes are similar. This
      may support that amblyopia is not a monocular disorder, but can affect both eyes.

PMID- 30284454
TI  - Associations of objective versus subjective social isolation with sleep
      disturbance, depression, and fatigue in community-dwelling older adults.
AB  - OBJECTIVE: Older adults are at higher risk of experiencing social isolation,
      which has been linked to impaired physical and mental health. The link between
      social isolation and health might be due to objective deprivation of social
      network and/or subjective experience of loneliness. This community-based cross
      sectional study examined whether the associations between social isolation and
      behavioral symptoms including sleep disturbance, depression, and fatigue are
      mostly explained by its subjective component. METHODS: Randomly selected 2541
      community-dwelling individuals in Los Angeles aged >=60 years were telephone
      interviewed regarding their objective and subjective social isolation
      (respectively social network size and loneliness), sleep disturbance, depression,
      and fatigue. RESULTS: When objective and subjective social isolation were
      separately included in multivariate regression models, both were significantly
      associated with behavioral symptoms. However, once they were simultaneously
      included in the same multivariate models, while subjective social isolation
      remained strongly associated (adjusted beta 0.24 for sleep disturbance [P <
      0.001], 0.44 for depression [P < 0.001], 0.17 for fatigue [P < 0.001]), objective
      social isolation was weakly or non-significantly associated (-0.04 for sleep
      disturbance [P = 0.03], -0.01 for depression [P = 0.48], -0.003 for fatigue [P =
      0.89]). Additionally, those with objective social isolation were found to have
      worse symptoms mostly when they also experienced subjective social isolation.
      CONCLUSIONS: Older adults with objective social isolation may experience sleep
      disturbance, depression, and fatigue because they feel socially isolated, not
      just because they are deprived of social networks. Interventions that target
      social isolation might serve as potential treatments for improving behavioral
      health of older adults, especially by targeting its subjective component.

PMID- 30284455
TI  - A Prospective Study on the Safety and Effectiveness of a Composite Sinus Stent
      for Use After Endoscopic Sinus Surgery.
AB  - Background The composite sinus stent was developed to support the nasal walls,
      stabilize the middle turbinate, and prevent adhesions following endoscopic sinus
      surgery (ESS). Objective This study sought to assess its safety and
      effectiveness. Methods A prospective clinical trial was conducted in a single
      medical center in 2016-2018. The study included 30 patients (64% males) with a
      mean age of 41.9 years, who were scheduled for bilateral ESS, were randomized to
      undergo composite sinus stent implantation for 14 to 28 days or middle meatus
      placement of a Telfa tampon for 2 to 3 days. Telfa is a nonadherent absorbent
      dressing that has been compared favorably with other packs for use following ESS.
      Both groups received the same postoperative treatment. Outcomes were evaluated
      endoscopically by the principal investigator and also by an independent
      investigator blinded to the intervention the patient had and by self-report
      questionnaires at 3 and 12 weeks postoperatively. Results The stent was
      successfully implanted and removed in all 29 treated sinuses, without
      complications. None of the stents showed granulation tissue or crusting. Compared
      to the tampon group, the stent group had significantly less inflammation (mean
      visual analog scale scores 0.2 vs 4.2 at 12 weeks, P = .01). The probability of
      having adhesion was 9.3 times greater in the control group compared to the study
      group ( P = .026), and middle turbinate lateralization rate at 12 weeks was 3.8%
      versus 44% in the study group and the control group, respectively, at 12 weeks (
      P = .006). Patients who underwent stent implantation experienced higher
      symptomatic improvement (Sino-Nasal Outcome Test 22 of -37.13 vs -28.07, P = .01,
      in study and control groups, respectively). During stent implantation (2-4
      weeks), patients did not suffer from any discomfort. Conclusions The composite
      sinus stent is safer and more effective than the Telfa tampon in maintaining
      sinus cavity patency and promoting healing following ESS.

PMID- 30284456
TI  - Evaluation of ocular motility deviation changes in exotropic patients after
      cycloplegic eye drops versus prism adaptation test.
AB  - PURPOSE: To evaluate changes in ocular motility deviation with cycloplegic eye
      drop examination compared to the prism adaptation test in patients with
      strabismus. METHODS: The medical charts were reviewed of all patients who
      underwent primary strabismus surgery in our center from December 2013 to July
      2015. Data collected included demographics, medical history, and findings on pre
      operative ophthalmic/orthoptic examination. Ocular motility deviation was
      measured before instillation of cycloplegic eye drops, immediately after maximal
      dilation (end point), and 10 and 20 min later. Prism adaptation test readings
      were taken at baseline, immediately after prism removal (end point), and 10 and
      20 min later. RESULTS: A total of 43 patients had complete pre- and post
      operative evaluations. Our analysis focused only on the exotropic patients (n =
      33). On cycloplegics, there was no significant difference in ocular motility
      deviation between baseline and end point for distance and near (p = 0.584, p =
      0.468, respectively). On prism adaptation test, comparison of ocular motility
      deviation between baseline and end point was statistically significant for
      distance and near (p = 0.002, p = 0.001, respectively). Changes remained
      significant 10 min after the end point for near (p = 0.011). Comparison at the
      end points between the tests revealed statistical significance for distance and
      near, favoring the prism adaptation test (p = 0.001 and p < 0.001, respectively).
      This significance was maintained even after 10 min for near (p = 0.036).
      CONCLUSION: The prism adaptation test is preferred over cycloplegic eye drops for
      the evaluation of maximal reserve of distance/near motility before surgical
      correction of exotropia.

PMID- 30284457
TI  - Qualitative Evaluation of High School Implementation Strategies for Youth Sports
      Concussion Laws.
AB  - CONTEXT: : All 50 states and the District of Columbia have enacted laws governing
      concussion management and education. These concussion laws, featuring common
      tenets regarding removal from play, return to play, and concussion education,
      have shaped school and district policies. OBJECTIVE: : To evaluate the strategies
      commonly used to implement concussion laws at the school and district levels, as
      reported by certified athletic trainers (ATs). DESIGN: : Qualitative study.
      SETTING: : High schools. PATIENTS OR OTHER PARTICIPANTS: : We interviewed 64 ATs
      from high schools (1 per school) participating in High School Reporting
      Information Online. DATA COLLECTION AND ANALYSIS: : Interviews were conducted
      with participants between April and October 2015 regarding implementation of the
      3 core tenets of concussion laws. Research team members independently evaluated
      the interview transcripts and field notes to identify common themes in
      implementation strategies. RESULTS: : Of the 64 schools represented, 90.6% were
      public schools, 89.1% sponsored more than 15 sports, and all schools employed at
      least 1 AT and had a written concussion policy. Four commonly used strategies to
      implement removal from play were reliance on coaches, immediate response,
      referral and guidance after injury, and notification of key individuals. Use of
      assessment or baseline tests, communication among parties involved, reliance on
      AT assessments, and return-to-learn policies were 4 frequent strategies to
      implement return to play. Finally, 3 major implementation strategies to
      effectuate concussion education were use of existing educational tools, timing of
      education, and concussion training for school professionals. CONCLUSIONS: :
      Although concussion laws were passed at different times and varied in content
      across states, common themes in implementation strategies emerged across
      jurisdictions. The identification of strategic approaches to implementation will
      help ensure proper concussion management and education, reducing negative health
      outcomes among youths with concussions.

PMID- 30284458
TI  - Epidemiology of Injuries Requiring Emergency Transport Among Collegiate and High
      School Student-Athletes.
AB  - CONTEXT: : Data regarding the epidemiology of emergency-transport incidents
      (ETIs) of patients with sport-related injuries are lacking. Understanding the use
      of emergency services by athletic trainers can help improve emergency
      preparedness and prehospital care for injured student-athletes. OBJECTIVE: : To
      determine the frequencies and types of ETIs resulting from athletic
      participation. DESIGN: : Descriptive epidemiology study. SETTING: : Participating
      colleges and high schools during 2009-2010 to 2014-2015 and 2011-2012 to 2013
      2014, respectively. PATIENTS OR OTHER PARTICIPANTS: : Student-athletes in 23 high
      school and 25 intercollegiate sports. MAIN OUTCOME MEASURE(S): : Data on injuries
      requiring emergency transport were collected by each team's athletic trainer via
      their respective online injury-tracking software. Athletic trainers also
      collected data on athlete-exposures (AEs). Emergency-transport incident
      frequencies and injury rates per 10 000 AEs with 95% confidence intervals (CIs)
      were reported. For each ETI, the sport, body part, injury mechanism, and final
      diagnosis were recorded. RESULTS: : A total of 339 and 146 ETIs were reported in
      collegiate and high school players, respectively. Collegiate women's ice hockey
      had the highest ETI rate (1.28/10 000 AEs; 95% CI = 0.71, 1.86). In high school,
      football had the highest rate at 0.80 per 10 000 AEs (95% CI = 0.64, 0.97).
      Athletes with head or face injuries required the most transports in college (n =
      71, 20.9%) and high school (n = 33, 22.6%) across all sports. Strains (n = 50,
      14.7%) and fractures (n = 35, 24.0%) were the leading diagnoses for patients
      undergoing transport in college and high school, respectively. CONCLUSIONS: :
      Athletic trainers should maintain a high level of emergency preparedness when
      working with sports that have high rates and numbers of ETIs. Athletes with
      injuries to the head/face required the most frequent transport across competition
      levels. Athletic trainers should have the appropriate equipment and protocols in
      place to handle these patients. Future researchers should examine the differences
      between field and hospital diagnoses to help improve prehospital care and
      decrease the likelihood of unnecessary emergency transports.

PMID- 30284459
TI  - Effects of Xiaoshuan Enteric-Coated Capsule on White and Gray Matter Injury
      Evaluated by Diffusion Tensor Imaging in Ischemic Stroke.
AB  - Xiaoshuan enteric-coated capsule (XSECC) is a drug approved by the Chinese State
      Food and Drug Administration for the treatment of stroke. This study was to
      investigate the effects of XSECC on white and gray matter injury in a rat model
      of ischemic stroke by diffusion tensor imaging (DTI) and histopathological
      analyses. The ischemia was induced by middle cerebral artery occlusion (MCAO).
      The cerebral blood flow measured by arterial spin labeling was improved by
      treatment with XSECC on the 3rd, 7th, 14th and 30th days after MCAO.
      Spatiotemporal white and gray matter changes in MCAO rats were examined with DTI
      derived parameters (fractional anisotropy, FA; apparent diffusion coefficient,
      ADC; axial diffusivity, lambda//; radial diffusivity, lambda?). The increased FA
      was found in the XSECC treatment group in the corpus callosum, external capsule
      and internal capsule, linked with the decreased lambda//, lambda? and ADC on the
      3rd day and reduced ADC on the 30th day in the external capsule, suggesting XSECC
      reduced the axon and myelin damage in white matter after stroke. The relative FA
      in the striatum, cortex and thalamus in XSECC treatment group was significantly
      increased on the 3rd, 7th, 14th and 30th days accompanied by the increased
      lambda// on the 3rd day and reduced relative ADC and lambda? on the 30th day,
      indicating that XSECC attenuated cell swelling and membrane damage in the early
      stage and tissue liquefaction necrosis in the late stage in gray matter after
      stroke. Additionally, XSECC-treated rats exhibited increased mean fiber length
      assessed by diffusion tensor tractography. Moreover, histopathological analyses
      provided evidence that XSECC relieved nerve cell and myelin damage in white and
      gray matter after stroke. Our research reveals that XSECC could alleviate white
      and gray matter injury, especially reducing nerve cell damage and promoting the
      repair of axon and myelin after ischemic stroke.

PMID- 30284460
TI  - Neuroprotective Action of Human Wharton's Jelly-Derived Mesenchymal Stromal Cell
      Transplants in a Rodent Model of Stroke.
AB  - Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs) have distinct
      immunomodulatory and protective effects against kidney, liver, or heart injury.
      Limited studies have shown that WJ-MSCs attenuates oxygen-glucose deprivation
      mediated inflammation in hippocampal slices. The neuroprotective effect of
      intracerebral WJ-MSC transplantation against stroke has not been well
      characterized. The purpose of this study was to examine the neuroprotective
      effect of human WJ-MSC (hWJ-MSC) transplants in an animal model of stroke. Adult
      male Sprague-Dawley rats were anesthetized and placed in a stereotaxic frame. hWJ
      MSCs, pre-labeled with chloromethyl benzamide 1,1'-dioctadecyl-3,3,3'3'-
      tetramethylindocarbocyanine perchlorate (CM-Dil), were transplanted to the right
      cerebral cortex at 10 min before a transient (60 min) right middle cerebral
      artery occlusion (MCAo). Transplantation of hWJ-MSCs significantly reduced
      neurological deficits at 3 and 5 days after MCAo. hWJ-MSC transplants also
      significantly reduced brain infarction and microglia activation in the penumbra.
      Grafted cells carrying CM-Dil fluorescence were identified at the grafted site in
      the ischemic core; these cells were mostly incorporated into ionized calcium
      binding adaptor molecule (+) cells, suggesting these xenograft cells were immuno
      rejected by the host. In another set of animals, hWJ-MSCs were transplanted in
      cyclosporine (CsA)-treated rats. hWJ-MSC transplants significantly reduced brain
      infarction, improved neurological function, and reduced neuroinflammation. Less
      phagocytosis of CM-dil-labeled grafted cells was found in the host brain after
      CsA treatment. Transplantation of hWJ-MSC significantly increased glia cell line
      derived neurotrophic factor expression in the host brain. Taken together, our
      data support that intracerebral transplantation of hWJ-MSCs reduced
      neurodegeneration and inflammation in the stroke brain. The protective effect did
      not depend on the survival of grafted cells but may be indirectly mediated
      through the production of protective trophic factors from the transplants.

PMID- 30284461
TI  - Sophora flavescens Containing-QYJD Formula Activates Nrf2 Anti-Oxidant Response,
      Blocks Cellular Transformation and Protects Against DSS-Induced Colitis in Mouse
      Model.
AB  - Qu-Yu-Jie-Du decoction (QYJD) is a commercially available traditional Chinese
      medicine (TCM). It is an aqueous extract of a Chinese herbal formula primarily
      consisting of eight TCM herbs: Taraxacum campylodes G.E. Haglund, Coix lacryma
      jobi L., Smilax glabra Roxb., Sanguisorba officinalis L, Styphnolobium japonicum
      (L.) Schott, Prunus persica (L.) Batsch, Sophora flavescens Aiton, and
      Eupolyphaga sinensis Walker. Matrine and oxymatrine are two of the major
      phytochemical constituents of QYJD. Inflammation and oxidative stress are
      strongly associated with colon carcinogenesis. Colorectal cancer (CRC) is the
      third most common type of cancer. Therefore, cancer chemopreventive agents
      targeting CRC are urgently needed. This study was conducted to investigate the
      potential anticancer effects and the underlying mechanisms of QYJD and its active
      constituents, matrine and oxymatrine, in human colon cancer HT29 cells and in a
      dextran sulfate sodium (DSS)-induced colitis mouse model. QYJD and matrine
      effectively inhibited the proliferation and anchorage-independent growth of HT29
      cells in a dose-dependent manner. QYJD and matrine also induced an Nrf2-mediated
      anti-oxidant response element-luciferase activity and upregulated the Nrf2
      mediated anti-oxidative stress genes HO-1 and NQO1 at both the mRNA and protein
      levels. In the DSS-induced colitis mouse model, QYJD reduced the disease activity
      index (DAI) and alleviated colonic shortening. Elevated Nrf2 and HO-1 mRNA levels
      were also observed in QYJD-treated mice. These findings showed that QYJD could
      elicit anti-inflammatory and anti-oxidative stress response in vitro in a cell
      line and in vivo in a DSS-induced colitis mouse model. These responses may
      contribute to the overall anticolon cancer effect of QYJD.

PMID- 30284462
TI  - Therapeutic Potential of Naringin for Intervertebral Disc Degeneration:
      Involvement of Autophagy Against Oxidative Stress-Induced Apoptosis in Nucleus
      Pulposus Cells.
AB  - Intervertebral disc degeneration (IDD) is a major cause of lower back pain, but
      few efficacious medicines have been developed for IDD. Increased nucleus pulposus
      cells apoptosis is a dominant pathogenesis of IDD and is considered a therapeutic
      target. Previously, our group proved that autophagy may protect nucleus pulposus
      cells against apoptosis. As one of the major bioflavonoids of citrus, naringin
      activates autophagy. Therefore, we hypothesize that naringin may have therapeutic
      potential for IDD by activating autophagy in nucleus pulposus cells. In this
      study, we evaluated the effects of naringin on TBHP-induced oxidative stress in
      nucleus pulposus cells in vitro as well as in puncture-induced rat IDD model in
      vivo. Our results showed that naringin could reduce the incidence of oxidative
      stress-induced apoptosis in nucleus pulposus cells and promoted the expression of
      autophagy markers LC3-II/I and beclin-1. Meanwhile, inhibition of autophagy by 3
      MA may partially reverse the anti-apoptotic effect of naringin, indicating that
      autophagy was involved in the protective effect of naringin in nucleus pulposus
      cells. Further study showed that autophagy regulation of naringin may be related
      to AMPK signaling. Also, we found that naringin treatment can regulate the
      expression of collagen II, aggrecan and Mmp13 to sustain the extracellular
      matrix. Furthermore, our in vivo study showed that naringin can ameliorate IDD in
      puncture-induced rat model. In conclusion, our study suggests that naringin can
      protect nucleus pulposus cells against apoptosis and ameliorate IDD in vivo, the
      mechanism may relate to its autophagy regulation.

PMID- 30284463
TI  - Progress in Experimental and Clinical Research of the Diabetic Retinopathy
      Treatment Using Traditional Chinese Medicine.
AB  - Diabetic retinopathy (DR), one of the most common microvascular complications of
      diabetic mellitus, is currently the main cause of adult-acquired blindness. The
      pathogenesis of DR is complex and the current clinical application of various
      treatment methods cannot completely prevent the development of this disease. Many
      reports have been published regarding the treatment of DR with Traditional
      Chinese Medicine (TCM), which has received increasing attention from medical
      practitioners worldwide. Studies published between 1994 and April 2017 were
      collected from the CNKI, VIP, Medline and Web of Science databases, as well as
      from Chinese traditional books and Chinese Pharmacopoeia, subsequently obtaining
      more than 550 studies. Thereafter, the status quo of DR treatment using TCM had
      been summarized according to four aspects - compound formula therapy, Chinese
      herbal medicine extracts and monomer therapy, integrated traditional Chinese and
      Western medicine therapy, and Chinese medicine external treatment. According to
      the literature reviewed herein, TCM has had definite effects on the prevention
      and treatment of DR, especially when used in combination with modern medical
      methods. However, the lack of a unified standard on the syndrome differentiation
      of DR and the lack of support of evidence-based medicine theory in clinical
      practice have been consistent concerns in previous research studies and needs to
      be addressed in subsequent studies.

PMID- 30284464
TI  - Chinese Herbal Medicine Glycyrrhiza inflataReduces Abeta Aggregation and Exerts
      Neuroprotection through Anti-Oxidation and Anti-Inflammation.
AB  - Amyloid [Formula: see text] (A[Formula: see text]) plays a major role in the
      pathogenesis of Alzheimer's disease (AD). The accumulation of misfolded
      A[Formula: see text] causes oxidative and inflammatory damage leading to
      apoptotic cell death. Chinese herbal medicine (CHM) has been widely used in
      clinical practice to treat neurodegenerative diseases associated with oxidative
      stress and neuroinflammation. This study examined the neuroprotection effects of
      CHM extract Glycyrrhiza inflata (G. inflata) and its active constituents,
      licochalcone A and liquiritigenin in AD. We examined A[Formula: see text]
      aggregation inhibition, anti-oxidation and neuroprotection in Tet-On A[Formula:
      see text]-GFP 293/SH-SY5Y cells and anti-inflammatory potential in
      lipopolysaccharide (LPS)-stimulated RAW 264.7 and LPS and interferon (IFN)
      [Formula: see text] (LPS/IFN-[Formula: see text])-activated BV-2 cells. In
      addition, we applied conditioned media (CM) of BV-2 cells primed with LPS/IFN
      [Formula: see text] to A[Formula: see text]-GFP SH-SY5Y cells to uncover the
      neuroprotective mechanisms. Our results showed that G. inflata extract and its
      two constituents displayed potentials of A[Formula: see text] aggregation
      inhibition and radical-scavenging in biochemical assays, A[Formula: see text]
      misfolding inhibition and reactive oxygen species (ROS) reduction in A[Formula:
      see text]-GFP 293 cells, as well as neurite outgrowth promotion,
      acetylcholinesterase inhibition and SOD2 up-regulation in A[Formula: see text]
      GFP SH-SY5Y cells. Meanwhile, both G. inflata extract and its constituents
      suppressed NO, TNF-[Formula: see text], IL-1[Formula: see text], PGE2 and/or Iba1
      productions in inflammation-stimulated RAW 264.7 or BV-2 cells. G. inflata
      extract and its constituents further protected A[Formula: see text]-GFP SH-SY5Y
      cells from BV-2 CM-induced cell death by ameliorating reduced BCL2 and
      attenuating increased IGFBP2, cleaved CASP3, BAD and BAX. Collectively, G.
      inflata extract, licochalcone A and liquiritigenin display neuroprotection
      through exerting anti-oxidative and anti-inflammatory activities to suppress
      neuronal apoptosis.

PMID- 30284465
TI  - Modified Ginseng Extract Induces Apoptosis in HepG2 Cancer Cells by Blocking the
      CXCL8-Mediated Akt/Nuclear Factor-[Formula: see text]B Signaling Pathway.
AB  - The cytokine C-X-C motif chemokine ligand 8 (CXCL8) is produced in the tumor
      microenvironment and has an important role in cancer pathogenesis. CXCL8
      activates the nuclear factor (NF)-[Formula: see text]B signaling. However, the
      role of NF-[Formula: see text]B inactivation in apoptosis induced by negative
      regulation of CXCL8 remains unclear. Here, we assessed the effects of MRGX on the
      transcriptional activity of NF-[Formula: see text]B and the expression of tumor
      necrosis factor (TNF)-[Formula: see text]-stimulated target genes in liver cancer
      cells. Furthermore, we found that modified regular ginseng extract (MRGX)
      mediated inhibition of NF-[Formula: see text]B signaling induced apoptosis.
      Importantly, MRGX exerted strong activity, inhibiting TNF-[Formula: see text]
      induced expression of Akt and NF-[Formula: see text]B in a concentration
      dependent manner. Furthermore, MRGX inhibited the TNF-[Formula: see text]-induced
      expression of genes encoding CXCL8, CXCL1, inducible nitric oxide synthase and
      intercellular adhesion molecule 1. MRGX also dowregulated Akt activation, and
      there was a significant decrease in Akt activation in HepG2 cells treated with
      CXCL8 siRNA. Conversely, CXCL8 overexpression increased Akt activation in MRGX
      treated HepG2 cells. When Akt was silenced, MRGX treatment of HepG2 cells
      overexpressing CXCL8 decreased nuclear translocation of NF-[Formula: see text]B,
      whereas Akt overexpression increased nuclear translocation of NF-[Formula: see
      text]B in MRGX-treated HepG2 cells. Moreover, MRGX negatively regulated the TNF
      [Formula: see text]-mediated I[Formula: see text]B/NF-[Formula: see text]B
      pathway to promote Bax activation, resulting in caspase-3 activation and
      apoptosis. Taken together, these results indicated that MRGX inhibited CXCL8
      mediated Akt/NF-[Formula: see text]B signaling, which upregulated Bax activation
      and consequently induced apoptosis in HepG2 cells.

PMID- 30284466
TI  - Activity Dependent Mammalian Target of Rapamycin Pathway and Brain Derived
      Neurotrophic Factor Release Is Required for the Rapid Antidepressant Effects of
      Puerarin.
AB  - Puerarin is a traditional Chinese medicine with beneficial effects of reduced
      depression-like behaviors in mice with stress. Previous studies also show that
      puerarin can produce neuroprotective effect via activating the Akt or increased
      brain-derived neurotrophic factor (BDNF) expression. Interestingly, BDNF and Akt
      downstream target, mammalian target of rapamycin (mTOR) mediate the fast-acting
      antidepressant properties of ketamine. Until now, the involvement of the mTOR
      signaling pathway or BDNF on puerarin-induced antidepressant effect remains
      unknown. We aimed to investigate whether the antidepressant-like effect induced
      by puerarin would associate mTOR signaling pathway and BDNF release. The
      antidepressant-like effects of puerarin were evaluated using the forced swim
      test. The activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionaic acid
      receptor (AMPAR)-mTOR signaling pathway and release of BDNF in the prefrontal
      cortex were determined. We also investigated the effect of puerarin on AMPAR
      trafficking through measuring the PKA phosphorylation of AMPAR subunit GluR1. Our
      present results show that puerarin exerted antidepressant-like responses that was
      mediated by AMPAR-induced mTOR signaling pathway and associated with increased
      BDNF release. Moreover, a significant increase in the GluR1 phosphorylation at
      its PKA site was noted following puerarin treatment. Our findings are the first
      to demonstrate that the antidepressant-like actions of puerarin require AMPAR
      mTOR signaling pathway activation, are associated with an increased BDNF level
      and facilitate AMPAR membrane insertion. These findings provide preclinical
      evidence that puerarin may possess antidepressant property which is mediated by
      the glutamatergic system.

PMID- 30284467
TI  - Antidepressant Effects of Vaccinium bracteatum via Protection Against Hydrogen
      Peroxide-Induced Oxidative Stress and Apoptosis.
AB  - The present study evaluates the anti-oxidative stress activity of Vaccinium
      bracteatum Thunb. fruit extract (VBFW) to identify the mechanisms responsible for
      its antidepressant-like effects. To evaluate the antidepressant and anti-oxidant
      effects of VBFW, malondialdehyde (MDA), serotonin transporter (SERT), and
      monoamine oxidase A (MAO-A) levels were measured in a mouse model of chronic
      restraint stress (CRS). The underlying mechanisms preventing oxidative stress and
      neuronal apoptosis were investigated using in vitro models of hydrogen peroxide
      (H2O[Formula: see text]-induced neuronal damage. The results showed that VBFW
      treatment (200[Formula: see text]mg/kg) significantly reduced MDA, SERT, and MAO
      A levels in the prefrontal cortex of CRS mice. Furthermore, VBFW (30[Formula: see
      text][Formula: see text]g/mL) exhibited protective effects against H2O2-induced
      cell death via inhibition of the H2O2-induced increase in Bax and decrease in Bcl
      2 levels within the mitochondria of SH-SY5Y cells. Furthermore, VBFW (10 and
      30[Formula: see text][Formula: see text]g/mL) exerted protective effects against
      H2O2-induced cell death through inhibition of key mitochondria-associated
      apoptotic proteins such as cytochrome c, caspase-3 and PARP. Additionally, VBFW
      (10 and 30[Formula: see text][Formula: see text]g/mL) could improve the activity
      of anti-oxidant enzymes (such as SOD and catalase) in H2O2-treated SH-SY5Y cells.
      These results suggest that the antidepressant and anti-oxidant effects of VBFW
      might be mediated by the regulation of SERT and MAO-A, and possibly associated
      with regulation of oxidative stress-induced apoptosis.

PMID- 30284468
TI  - Allyl Isothiocyanate Induces Autophagy through the Up-Regulation of Beclin-1 in
      Human Prostate Cancer Cells.
AB  - Allyl isothiocyanate (AITC), one of the most widely studied phytochemicals,
      inhibits the survival of human prostate cancer cells while minimally affecting
      normal prostate epithelial cells. Our study demonstrates the mechanism of AITC
      induced cell death in prostate cancer cells. AITC induces autophagy in RV1 and
      PC3 cells, judging from the increased level of LC3-II protein in a dose- and time
      dependent manner, but not in the normal prostate epithelial cell (PrEC).
      Inhibition of autophagy in AITC-treated cells decreased cell viability and
      enhanced apoptosis, suggesting that the autophagy played a protective role. There
      are several pathways activated in ATIC-treated cells. We detected the
      phosphorylation forms of mTOR, ERK, AMPK, JNK and p38, and ERK AMPK and JNK
      activation were also detected. However, inhibition of AITC-activated ERK, AMPK
      and JNK by pre-treatment of specific inhibitors did not alter autophagy
      induction. Finally, increased beclin-1 expression was detected in AITC-treated
      cells, and inhibition of AITC-induced beclin-1 attanuated autophagy induction,
      indicating that AITC-induced autophagy occurs through upregulating beclin-1.
      Overall, our data show for the first time that AITC induces protective autophagy
      in Rv1 and PC3 cells through upregulation of beclin-1. Our results could
      potentially contribute to a therapeutic application of AITC in prostate cancer
      patients.

PMID- 30284469
TI  - Regulating Gut Flora Dysbiosis in Obese Mice by Electroacupuncture.
AB  - Recently, gut flora has been linked to the onset of obesity and has been shown to
      influence the host's metabolism. Acupuncture is a well-known agent used for the
      treatment of numerous diseases such as obesity. This study aimed to explore the
      impacts of electroacupuncture treatment on gut microbiota composition and
      function in obese mice. Pyrosequencing of 16S rRNA genes and Metagenomic analysis
      of the fecal microbiota were used for this purpose. The basic parameters of body
      weight, Lee's index, serum lipid and epididymal adipose weight were ameliorated
      significantly after introducing an electroacupuncture intervention.
      Acidobacteria, Cyanobacteria and Basidiomycota (Normal group) and Fusobacteria,
      Firmicutes and Spirochmycetes (Model group) were remarkably affluent at the
      phylum level. Bacteroides sp. CAG: 927 and Prevotella sp. CAG: 1031 (Normal
      group), Lachnospiraceae bacterium and Helicobacter rodentium (Model group) at the
      species level were distinctly enriched. The structures and functions of the
      intestinal flora were significantly different between healthy and obese mice, and
      animals in the acupuncture group gradually tended towards healthy controls.
      Moreover, electroacupuncture altered the bacterial diversity and metabolic genes
      to establish new balance, observed the obvious change from 7[Formula: see text]d
      and stabilized gradually through 21[Formula: see text]d. These findings suggested
      gut flora could be a novel target of electroacupuncture treatment against
      obesity.

PMID- 30284470
TI  - Marsdenia tenacissima: A Review of Traditional Uses, Phytochemistry and
      Pharmacology.
AB  - The stems and roots of Marsdenia tenacissima (Roxb.) Wight et Arn., a traditional
      Chinese medicine and Dai herbal medicine, have been widely used for the treatment
      of asthma, trachitis, tonsillitis, pharyngitis, cystitis, pneumonia and drug or
      food poisoning. Nowadays, the extract of Marsdenia tenacissima, under the
      trademark of "Xiao-ai-ping", is widely used in clinic for the treatment of
      different cancers in China. To date, approximately 196 chemical ingredients
      covering steroids, triterpenes and organic acids have been identified from
      different parts of this plant. Steroids are the major characteristic and
      bioactive constituents of this plant. Modern pharmacology has demonstrated that
      the crude extracts and steroids have various in vitro and in vivo pharmacological
      activities, such as multidrug resistance reversal, antitumor, anti-angiogenic,
      immunomodulation and anti-HIV activities. The multidrug resistance reversal of
      steroids provided evidence for the use of this herb in clinic. However, despite
      wide clinical application, clinical trials, quality control method,
      pharmacokinetic and toxicity research on Marsdenia tenacissima were seldom
      reported and deserved further efforts. The present review aimed to achieve a
      comprehensive and up-to-date investigation in ethnopharmacology, phytochemistry,
      pharmacology, clinical study, pharmacokinetics, toxicology and quality control of
      Marsdenia tenacissima. In addition, the possible perspectives and trends for
      future studies of Marsdenia tenacissima have also been put forward. It is
      believed that this review would provide a theoretical basis and valuable data for
      future in-depth studies and applications.

PMID- 30284472
TI  - Surgical closure of giant traumatic macular hole with retinal graft.
AB  - AIM: To present a case with a large traumatic macular hole that we repaired with
      a retinal graft. CASE DESCRIPTION: A 24-year-old male patient presented with
      corneal penetration and an intraocular foreign body caused by a work accident.
      Vitrectomy and intraocular foreign body removal were performed. One month after
      the surgery, the patient had macula on retinal detachment in the nasal and
      superior quadrant. In addition, a giant macular hole was formed. However, the
      macula was atrophic because of the trauma, and we could not repair the hole with
      classic macular hole surgery techniques. For this reason, we used a retinal graft
      to cover the macular hole, and we observed that the hole was closed in follow-up
      visits. CONCLUSION: Retinal grafts can be used in patients with giant macular
      holes. They may be useful especially in patients with atrophic macula in trauma
      cases.

PMID- 30284471
TI  - Operative Treatment of the Cavovarus Foot.

PMID- 30284473
TI  - SLX4: multitasking to maintain genome stability.
AB  - The SLX4/FANCP tumor suppressor has emerged as a key player in the maintenance of
      genome stability, making pivotal contributions to the repair of interstrand cross
      links, homologous recombination, and in response to replication stress genome
      wide as well as at specific loci such as common fragile sites and telomeres. SLX4
      does so in part by acting as a scaffold that controls and coordinates the XPF
      ERCC1, MUS81-EME1, and SLX1 structure-specific endonucleases in different DNA
      repair and recombination mechanisms. It also interacts with other important DNA
      repair and cell cycle control factors including MSH2, PLK1, TRF2, and TOPBP1 as
      well as with ubiquitin and SUMO. This review aims at providing an up-to-date and
      comprehensive view on the key functions that SLX4 fulfills to maintain genome
      stability as well as to highlight and discuss areas of uncertainty and emerging
      concepts.

PMID- 30284475
TI  - Three-dimensional nanofiberous PLLA/PCL scaffold improved biochemical and
      molecular markers hiPS cell-derived insulin-producing islet-like cells.
AB  - Nanofibrous scaffolds are considered as a new strategy for Type 1 diabetes
      mellitus therapy. We used a hybrid of poly-l-lactic acid (PLLA) and
      polycaprolactone (PCL) as three-dimensional (3D) culture models for
      differentiation of human induced pluripotent stem cells (hiPSCs) to beta islet
      like cluster cell compared with routine culture (2D). Morphological changes of
      cells were checked by microscope. mRNA endodermal SOX-17 on day 7 and pancreatic
      gene markers Pdx1, glucagon and Glut2 were evaluated on day 23 by qPCR. As well
      as, insulin and C-peptide protein expression was evaluated by immunocytochemistry
      staining. In addition, insulin and C-peptide secretion in various glucose
      concentrations was evaluated by ELISA. Light and scanning electron microscopy
      (SEM) microscope showed changes in induced cells. In tandem, these modifications
      were more evident in 3 D culture. Pdx1, Glucagon and Glut2 markers in PLLA/PCL
      were significantly higher in 3 D culture. In addition, qualitative
      immunochemistry showed that insulin and C-peptide were expressed in 2 D and 3 D
      culture medium. Furthermore, evaluation of insulin and C-peptide clarified that
      secretion of these proteins in PLLA/PCL scaffold were statistically different in
      2 D and 3 D strategies. These findings suggest that functional matured induction
      cells on PLLA/PCL scaffold can be used for islet beta cell therapy and
      regenerative medicine.

PMID- 30284474
TI  - Inhibition of p38 mitogen-activated protein kinase exerts a hypoglycemic effect
      by improving beta cell function via inhibition of beta cell apoptosis in db/db
      mice.
AB  - The p38 mitogen-activated protein kinase (MAPK) pathway is involved in
      endoplasmic reticulum stress (ERS) and inflammation, which may play an important
      role in the pathogenesis of type 2 diabetes (T2DM). This study aimed to
      investigate whether p38 MAPK contributes to the pathogenesis of T2DM. 6-week-old
      female db/db mice were randomly assigned to Dmo and Dmi groups, and C57 mice were
      assigned as controls. The Dmi group was gavaged with the p38 MAPK inhibitor
      SB203580 for 9 weeks, and the effects on beta cell dysfunction and apoptosis were
      investigated. db/db mice showed higher food intake, body mass, fasting glucose,
      and plasma insulin levels than C57 mice. After SB203580 administration, blood
      glucose was significantly lower. HOMA beta and HOMA IR were improved. Islet mRNA
      expression levels of the ERS markers were lower. P38 MAPK inhibition reduced
      blood glucose and improved beta cell function, at least in part by reducing beta
      cell apoptosis.

PMID- 30284476
TI  - Refractive predictability and visual outcomes of an extended range of vision
      intraocular lens in eyes with previous myopic laser in situ keratomileusis.
AB  - PURPOSE: To evaluate the refractive predictability obtained with an extended
      range of vision intraocular lens in eyes with previous myopic laser in situ
      keratomileusis, confirming which intraocular lens power formula provides the most
      accurate calculation. METHODS: The study enrolled 71 eyes with previous
      successful myopic laser in situ keratomileusis surgery of 43 patients undergoing
      cataract surgery with implantation of the extended range of vision intraocular
      lens TECNIS Symfony (Johnson and Johnson Vision). Intraocular lens power was
      calculated using all American Society of Cataract and Refractive Surgeons
      formulas, and their average value was selected for implantation. Refractive
      outcomes were evaluated at 3 months postoperatively. RESULTS: Postoperative
      spherical equivalent within +/-0.50 and +/-1.00 D was found in 61.6% and 86.3% of
      eyes, respectively. In eyes with pre-laser in situ keratomileusis data available,
      no significant correlation was found between pre-laser in situ keratomileusis
      spherical equivalent and post-cataract surgery spherical equivalent (r = 0.237, p
      = 0.114). A postoperative spherical equivalent within +/-0.50 D was found in
      65.2% and 55.6% of eyes in the subgroups with and without pre-laser in situ
      keratomileusis data available, respectively (p = 0.480). Statistically
      significantly higher differences between the intraocular lens power implanted and
      the calculation provided by the Potvin-Hill (p = 0.028) and Barrett True K No
      History formulas (p = 0.022) were found in those eyes with postoperative
      spherical equivalent > 0.50 D. CONCLUSION: The extended range of vision
      intraocular lens evaluated can provide a predictable refractive correction in
      eyes with previous laser in situ keratomileusis surgery. The Potvin-Hill and
      Barrett True K No History are the most adequate formulas to perform intraocular
      lens power calculations in these cases.

PMID- 30284477
TI  - Assay of miRNA in cell samples using enhanced resonance light scattering
      technique based on self aggregation of magnetic nanoparticles.
AB  - AIMS: miRNAs are regarded as potential biomarkers correlated with the development
      and progression of many diseases. However, it is a challenge to construct a
      sensitive method to detect them without using time-consuming radioactive labeling
      or complex amplification strategies. METHODS: A facile resonance light scattering
      (RLS) system was developed for the detection of miRNA employing magnetic
      nanoparticles (MNPs) as RLS probes. MNPs were coated with streptavidin. DNA
      probes were modified on the surface of MNPs based on the specific interaction of
      streptavidin and biotin forming MNPs@DNA probes. MNPs@DNA probes dispersed in
      homogeneous media causing low RLS signal. RESULTS & CONCLUSION: miRNA hybridized
      with DNA probes resulting in the aggregation of MNPs and inducing the enhancement
      of RLS intensity. miRNAs were determined successfully with limit of detection at
      0.9 picomole per liter (pM). The potential clinical application of the present
      biosensor was also demonstrated by measuring miRNAs in human normal and cancer
      cells, and human serum samples.

PMID- 30284478
TI  - Responsiveness of the PROMIS and FAAM Instruments in Foot and Ankle Orthopedic
      Population.
AB  - BACKGROUND: Investigating the responsiveness of an instrument is important in
      order to provide meaningful interpretation of clinical outcomes. This study
      examined the responsiveness of the Patient-Reported Outcomes Measurement
      Information System (PROMIS) Physical Function (PF), the PROMIS Pain Interference
      (PI), and the Foot and Ankle Ability Measure (FAAM) Sports subscale in an
      orthopedic sample with foot and ankle ailments. METHODS: Patients presenting to
      an orthopedic foot and ankle clinic during the years 2014-2017 responded to the
      PROMIS and FAAM instruments prior to their clinical appointments. The
      responsiveness of the PROMIS PF v1.2, PROMIS PI v1.1, and FAAM Sports were
      assessed using paired samples t test, effect size (ES), and standardized response
      mean (SRM) at 4 different follow-up points. A total of 785 patients with an
      average age of 52 years (SD = 17) were included. RESULTS: The PROMIS PF had ESs
      of 0.95 to 1.22 across the 4 time points (3, >3, 6, and <6 months) and SRMs of
      1.04 to 1.43. The PROMIS PI had ESs of 1.04 to 1.63 and SRMs of 1.17 to 1.23. For
      the FAAM Sports, the ESs were 1.25 to 1.31 and SRMs were 1.07 to 1.20. The
      ability to detect changes via paired samples t test provided mixed results. But
      in general, the patients with improvement had statistically significant improved
      scores, and the worsening patients had statistically significant worse scores.
      CONCLUSION: The PROMIS PF, PROMIS PI, and FAAM Sports were sensitive and
      responsive to changes in patient-reported health. LEVEL OF EVIDENCE: Level II,
      prospective comparative study.

PMID- 30284479
TI  - Politics and palliative care: Rwanda.
AB  - Dion Smyth's review of palliative nursing on the internet.

PMID- 30284480
TI  - Photojournalism-Based Intervention Reduces Caregiver Burden and Depression in
      Alzheimer's Disease Family Caregivers.
AB  - PURPOSE: Art interventions have demonstrated holistic benefits for persons living
      with dementia and their caregivers. In this article, we describe the results of a
      pilot photojournalism program for 10 unpaid caregivers of persons living with
      dementia, with respect to caregivers' experience in the program and their
      psychological well-being. DESIGN: Caregivers participated in four sessions led by
      a professional photojournalist who taught principles of photography. Between the
      sessions, caregivers took photographs that represented what caregiving meant to
      them using digital cameras provided in the program. During the sessions,
      instruction was interspersed with discussion of caregivers' photographs. METHOD:
      Caregiver burden and depressive symptoms were measured pre- and postprogram.
      Qualitative exploration included sessions' observations, viewing caregivers'
      photographs, and recording caregivers' accompanying comments. FINDINGS: For
      participants with pre- and postprogram data, caregiver burden decreased
      significantly ( p = .037). For caregivers with pre- and postprogram data,
      depressive symptoms decreased nonsignificantly ( p = .066). Clinically meaningful
      reductions in caregiver burden and depressive symptoms were attained. Qualitative
      findings highlighted caregivers' strong engagement with the project, the
      facilitator, and other participants, and reflection on multiple aspects of their
      experience. CONCLUSIONS: This intervention helped caregivers creatively
      communicate their experience and demonstrated efficacy in the improvement of
      caregivers' psychological well-being.

PMID- 30284481
TI  - Combining SERS analysis of serum with PSA levels for improving the detection of
      prostate cancer.
AB  - AIM: Previous studies regarding surface-enhanced Raman scattering (SERS) of serum
      have shown promising initial results in discriminating prostate cancer, a
      strategy which could complement standard tests such as the prostate-specific
      antigen (PSA). MATERIALS & METHODS: SERS spectra of serum samples were combined
      with serum PSA levels to improve the discrimination accuracy between prostate
      cancer and nonmalignant pathologies in a cohort of 54 patients using principal
      component analysis-linear discriminant analysis (PCA-LDA). RESULTS & DISCUSSION:
      Combining SERS spectra with serum PSA levels in a single PCA-LDA model could
      discriminate between the two groups with an overall accuracy of 94%, yielding
      better results than either method alone. CONCLUSION: These results highlight that
      combining SERS-based cancer screening with serum PSA levels represents a
      promising strategy for improving the accuracy of prostate cancer diagnosis.

PMID- 30284482
TI  - A Safety and Cost Analysis of Outpatient Versus Inpatient Hindfoot Fusion
      Surgery.
AB  - BACKGROUND: Hindfoot fusion procedures are increasingly being performed in the
      outpatient setting. However, the cost savings of these procedures compared with
      the risks and benefits has not been clearly investigated. The objective of this
      study was to compare patient characteristics, costs, and short-term complications
      between inpatient and outpatient procedures. METHODS: This was a retrospective
      review of all patients who underwent inpatient and outpatient hindfoot fusion
      procedures by a single surgeon, at 1 academic institution, from 2013 to 2017.
      Data collected included demographics, operative variables, comorbidities,
      complications, costs, and subsequent reencounters. RESULTS: Of 124 procedures, 34
      were inpatient and 90 were outpatient. Between procedural settings, with the
      numbers available, there was no significant increase in complication rate or
      frequency of reencounters within 90 days. There were no significant differences
      in the number of patients with reencounters related to the index procedure within
      90 days (P = .43). There were 30 reencounters within 90 days after outpatient
      surgery versus 4 after inpatient surgery (P = .05). The total number of emergency
      room visits in the outpatient group within 90 days was significantly higher
      compared with the inpatient group (P = .04). The average cost for outpatient
      procedures was US$4159 less than inpatient procedures (P < .0001). CONCLUSION:
      Outpatient hindfoot fusion may be a safe alternative to inpatient surgery, with
      significant overall cost savings and similar rate of short-term complications. On
      the basis of these findings, we believe that outpatient management is preferable
      for the majority of patients, but further investigation is warranted. LEVELS OF
      EVIDENCE: Level III.

PMID- 30284483
TI  - Collagen coated electrospun polyethersulfon nanofibers improved insulin producing
      cells differentiation potential of human induced pluripotent stem cells.
AB  - Given the current conditions of life, one of the problems that the world is
      facing and is rapidly expanding is diabetes. The existing treatment methods are
      not responsive to these patients. Today, due to the advent of tissue engineering,
      cell and stem cell therapies, there are many hopes for treating these patients.
      In the present study, Polyethersulfone (PES) nanofibers were fabricated by
      electrospinning and then coated by collagen (PES-collagen), since this protein is
      abundant at the pancreatic extracellular matrix. After scaffold characterization,
      pancreatic differentiation potential of human induced pluripotent stem cells
      (hiPSCs) was investigated when cultured on PES-collagen by RT-qPCR,
      Immunofluorescence staining and insulin and C-peptide release assays. Pancreatic
      genes and proteins in cultured iPSCs on PES-collagen were expressed significantly
      higher than those cultured on culture plate as 2 D control group. Although
      differentiated cells in both groups are functional and secrete C-peptide and
      insulin in response to glucose challenges according to the immunoassay result.
      Considered together, PES-collagen demonstrated that it can be effective during
      pancreatic differentiation of the stem cells and can also be considered as a
      promising candidate for use in pancreatic tissue engineering application.

PMID- 30284484
TI  - Nanoparticle-mediated delivery of Tanshinone IIA reduces adverse cardiac
      remodeling following myocardial infarctions in a mice model: role of NF-kappaB
      pathway.
AB  - Our previous works have shown that tanshinone IIA inhibited maladaptive
      extracellular matrix remodeling in cardiac fibroblasts implicating its potential
      role in treating of pathologic cardiac remodeling. However, the intrinsically
      poor solubility and bioavailability of tanshinone IIA hindered its clinical
      application. Here we develop monomethoxy-poly (ethylene glycol)-poly (lactic
      acid)-D-alpha-Tocopheryl polyethylene glycol 1000 succinate (mPEG-PLA-TPGS)
      nanoparticle incorporating tanshinone IIA (tanshinone IIA-NPs) and study its
      efficacy in post-infarction left ventricular (LV) remodeling. Male C57BL/6 mice
      underwent left coronary artery ligation followed by subsequent intravenously
      injected tanshinone IIA-NPs therapy for 5 consecutive days. Treatment with
      tanshinone IIA-NP improved cardiac function, limited infarct expansion, and
      prevented left ventricle dilation at 4 weeks post-MI. Furthermore, cardiomyocytes
      inflammation, apoptosis and myocardial fibrosis were significantly attenuated in
      tanshinone IIA-NP treated mice. These effects also correlated with inhibition of
      IkappaB protein phosphorylation and NF-kappaB activation, leading to suppression
      of proinflammatory cytokine expression. Together, these results demonstrate
      tanshinone IIA-NP attenuated adverse cardiac remodeling and dysfunction mediated
      through prevention of IkappaB phosphorylation and NF-kappaB activation.
      Tanshinone IIA-NP is a novel approach to treat myocardial IR injury in patients
      with MI.

PMID- 30284485
TI  - Pharmacophore-based discovery of 2-(phenylamino)aceto-hydrazides as potent
      eosinophil peroxidase (EPO) inhibitors.
AB  - There is an increasing interest in developing novel eosinophil peroxidase (EPO)
      inhibitors, in order to provide new treatment strategies against chronic
      inflammatory and neurodegenerative diseases caused by eosinophilic disorder.
      Within this study, a ligand-based pharmacophore model for EPO inhibitors was
      generated and used for in silico screening of large 3 D molecular structure
      databases, containing more than 4 million compounds. Hits obtained were clustered
      and a total of 277 compounds were selected for biological assessment. A class of
      2-(phenyl)amino-aceto-hydrazides with different substitution pattern on the
      aromatic ring was found to contain the most potent EPO inhibitors, exhibiting
      IC50 values down to 10 nM. The generated pharmacophore model therefore,
      represents a valuable tool for the selection of compounds for biological testing.
      The compounds identified as potent EPO inhibitors will serve to initiate a hit to
      lead and lead optimisation program for the development of new therapeutics
      against eosinophilic disorders.

PMID- 30284486
TI  - Design, synthesis and biological evaluation of tricyclic pyrazolo[1,5
      c][1,3]benzoxazin-5(5H)-one scaffolds as selective BuChE inhibitors.
AB  - Based on the structural analysis of tricyclic scaffolds as butyrylcholinesterase
      (BuChE) inhibitors, a series of pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one
      derivatives were designed, synthesized and evaluated for their
      acetylcholinesterase (AChE) and BuChE inhibitory activity. Compounds with 5
      carbonyl and 7- or/and 9-halogen substitutions showed potential BuChE inhibitory
      activity, among which compounds 6a, 6c and 6g showed the best BuChE inhibition
      (IC50 = 1.06, 1.63 and 1.63 uM, respectively). The structure-activity
      relationship showed that the 5-carbonyl and halogen substituents significantly
      influenced BuChE activity. Compounds 6a and 6g were found nontoxic, lipophilic
      and exhibited remarkable neuroprotective activity and mixed-type inhibition
      against BuChE (Ki = 7.46 and 3.09 uM, respectively). Docking studies revealed
      that compound 6a can be accommodated into BuChE via five hydrogen bonds, one Pi
      Sigma interaction and three Pi-Alkyl interactions.

PMID- 30284489
TI  - Wide-range effects of the MALT-1 inhibitor Mi-2 in CLL cells results in
      apoptosis.

PMID- 30284488
TI  - The diverse role of TIGAR in cellular homeostasis and cancer.
AB  - TP53-induced glycolysis and apoptosis regulator (TIGAR) is a p53 target protein
      that plays critical roles in glycolysis and redox balance. Accumulating evidence
      shows that TIGAR is highly expressed in cancer. TIGAR redirects glycolysis and
      promotes carcinoma growth by providing metabolic intermediates and reductive
      power derived from pentose phosphate pathway (PPP). The expression of TIGAR in
      cancer is positively associated with chemotherapy resistance, suggesting that
      TIGAR could be a novel therapeutic target. In this review, we briefly presented
      the function of TIGAR in metabolic homeostasis in normal and cancer cells.
      Finally, we discussed the future directions of TIGAR research in cancer.

PMID- 30284487
TI  - Discovering a new class of antifungal agents that selectively inhibits microbial
      carbonic anhydrases.
AB  - Infections caused by pathogens resistant to the available antimicrobial
      treatments represent nowadays a threat to global public health. Recently, it has
      been demonstrated that carbonic anhydrases (CAs) are essential for the growth of
      many pathogens and their inhibition leads to growth defects. Principal drawbacks
      in using CA inhibitors (CAIs) as antimicrobial agents are the side effects due to
      the lack of selectivity toward human CA isoforms. Herein we report a new class of
      CAIs, which preferentially interacts with microbial CA active sites over the
      human ones. The mechanism of action of these inhibitors was investigated against
      an important fungal pathogen, Cryptococcus neoformans, revealing that they are
      also able to inhibit CA in microbial cells growing in vitro. At our best
      knowledge, this is the first report on newly designed synthetic compounds
      selectively targeting beta-CAs and provides a proof of concept of microbial CAs
      suitability as an antimicrobial drug target.

PMID- 30284490
TI  - Membrane sweeping at term to promote spontaneous labour and reduce the likelihood
      of a formal induction of labour for postmaturity: a systematic review and meta
      analysis.
AB  - The aim of this study was to evaluate the efficacy and the safety of membrane
      sweeping in promoting spontaneous labour and reducing a formal induction of
      labour for postmaturity. Based on articles published between 2005 and 2016, 12
      electronic databases were searched. Relative risk (RR) and its 95% confidence
      interval (CI) were used as pooled statistics. A total of seven studies consisting
      of 2252 participants were selected for the review and meta-analysis. The results
      revealed that membrane sweeping is advantageous in promoting spontaneous labour
      (RR = 1.205, 95% CI: 1.133-1.282, p = <.001), and reducing the formal induction
      of labour for postmaturity (RR = 0.523, 95% CI: 0.409-0.669, p = <.001). The
      studies reported several varying outcomes for both maternal and foetal
      morbidities; meta-analyses were performed where possible on each of these and
      found there to be no statistically significant differences in outcome between the
      intervention and control groups. Impact Statement What is already known on this
      subject? Research suggests that a pregnancy which exceeds 42 weeks of gestation
      is associated with an increased risk of perinatal morbidity and mortality
      (Gulmezoglu et al. 2012 ). Consequently, a formal induction of labour is usually
      offered to low-risk pregnant women between 41 and 42 weeks of pregnancy. However,
      all of the induction methods carry some degree of risk in terms of the associated
      morbidities and effectiveness (Cunningham 2005 ; Simpson and James 2008 ; Thomas
      et al. 2014 ), as well as having an impact on NHS resources (Department of Health
      2015 ), and the birth experience of women (Gatward et al. 2010 ). For these
      reasons, it is currently recommended by The National Institute for Health and
      Care Excellence (NICE 2008 ) that women are offered a membrane sweep to promote
      spontaneous labour prior to arranging a formal induction of labour. What the
      results of this study add? The results from this meta-analysis add to the body of
      existing evidence around membrane sweeping. This study clearly demonstrates that
      membrane sweeping is effective in promoting a spontaneous labour and thereby
      reducing the need for a formal induction of labour. However, the results of this
      review suggest that this effect is significant from 38 weeks of gestation, and is
      not dependent upon the number or timing of membrane sweeps performed. What the
      implications are of these findings for clinical practice and/or further research?
      There is no evidence supporting any increase in maternal or foetal morbidity
      suggesting that membrane sweeping is a safe procedure to offer to all low risk
      pregnant women. We recommend therefore that there could be a reduction in the
      gestation at which membrane sweeping is offered from 40 weeks for primiparous
      women and 41 weeks for multiparous women to 38 weeks onwards for all low risk
      women without any increased risk of maternal or foetal morbidity. This may result
      in a decreased risk of requiring a formal induction of labour for postmaturity.

PMID- 30284492
TI  - Clinical Outcomes and Complications of Midfoot Charcot Reconstruction With
      Intramedullary Beaming.
AB  - BACKGROUND: The purpose of this study was to examine the clinical outcomes and
      complications of patients with midfoot Charcot managed with midfoot osteotomy,
      realignment arthrodesis, and stabilization using intramedullary beams. METHODS:
      Consecutive patients with midfoot Charcot treated at a tertiary-care foot and
      ankle center from January 2013 to July 2016 who underwent corrective osteotomy
      with internal beam fixation were identified; 25 patients were included in the
      final analysis. Patients with a minimum 1-year follow-up were evaluated with
      physical examination, weightbearing radiographs, and patient-reported outcome
      measures. The primary outcome measure was defined as restoration of a stable,
      plantigrade, ulcer-free foot. Median age was 58 years, median BMI was 32, and 80%
      were diabetic (75% insulin-dependent). RESULTS: An ulcer-free, stable,
      plantigrade foot was obtained in 84% of patients. The radiographic lateral and
      anteroposterior Meary angle medians improved 9 degrees  and 15 degrees ,
      respectively, from preoperative to final postoperative weightbearing measurements
      ( P < .001 and P = .02). Overall, 46% of midfoot osteotomies were united on final
      radiographs at a median 18-month radiographic follow-up. Deep infection developed
      in 6 (24%) patients. The presence of a preoperative ulcer was found to be
      predictive of postoperative infection (P = .04); all 6 deep infections occurred
      in patients with preoperative ulceration. Four (16%) patients progressed to
      amputation at a mean 15 postoperative months, all for deep infection. CONCLUSION:
      Midfoot Charcot reconstruction with intramedullary beaming allowed for
      restoration of an ulcer-free, plantigrade foot in most patients, but the
      complication rates were high, especially in patients with preoperative
      ulceration. LEVEL OF EVIDENCE: Level IV, retrospective case series.

PMID- 30284493
TI  - Identifying ovulatory cycles and the day of ovulation by the mis-use of
      pregnanediol glucuronide excretion rate thresholds.

PMID- 30284491
TI  - Comparison of Two Different Techniques for Isolated Left Subclavian Artery
      Revascularization During Thoracic Endovascular Aortic Repair in Zone 2.
AB  - PURPOSE: To analyze the results of isolated left subclavian artery (LSA)
      revascularization during thoracic endovascular aortic repair (TEVAR) using
      carotid-subclavian bypass (CSbp) or chimney grafts (CGs). METHODS: A
      retrospective multicenter, observational study identified 73 patients (mean age
      68+/-13 years, range 22-87; 56 men) with acute or chronic thoracic aortic lesions
      who underwent TEVAR with isolated LSA revascularization using either CSbp (n=42)
      or CGs (n=31) from January 2010 and February 2017. Primary endpoints were TEVAR
      related mortality, postoperative stroke, freedom from type Ia endoleak, and LSA
      patency. RESULTS: Primary technical success was achieved in all cases. Early
      TEVAR-related mortality was 4.2% (CSbp 2% vs CG 6%, p=0.571). Two (3%) patients
      had major ischemic strokes (one in each group). Mean follow-up was 24+/-21 months
      (range 1-72; median 15). Estimated freedom from TEVAR-related mortality was 93%+/
      3% (95% CI 84.3% to 97.0%) at 12 and 36 months, with no significant difference
      between CSbp and CG (p=0.258). Aortic reintervention did not differ between the
      groups (CSbp 5% vs CG 6%, p=0.356); nor did freedom from type Ia endoleak (CSbp
      98% vs CG 87%, p=0.134). Gutter-related endoleaks occurred in 4 (13%) CG
      patients, but none of the patients experienced sac enlargement or the need for
      reintervention and none died. Primary patency of the LSA was 100% for the entire
      group during the observation period. CONCLUSION: In our experience, LSA
      revascularization proved most satisfactory and equally effective with both the
      CSbp and CG techniques, without discernible differences at midterm follow-up.

PMID- 30284494
TI  - Would antioxidant-loaded nanoparticles present an effective treatment for
      ischemic stroke?
AB  - Ischemic stroke is a leading cause of death and disability worldwide and is in
      urgent need of new treatment options. The only approved treatment for stroke
      restores blood flow to the brain, but much of the tissue damage occurs during the
      subsequent reperfusion. Antioxidant therapies that directly address ischemia
      reperfusion injury have shown promise in preclinical results. In this review, we
      discuss that reformulating antioxidant therapies as nanomedicine can potentially
      overcome the barriers that have kept these therapies from succeeding in the
      clinic. We begin by reviewing the pathophysiology of ischemic stroke with a focus
      on the effects of reperfusion injury. Next, we review nanotherapeutic systems
      designed to treat the disease with a focus on those addressing reperfusion
      injury. Mechanisms of passive and active transport required to traverse a blood
      brain barrier are discussed. Finally, we conclude by outlining design parameters
      for potentially successful nanomedicines as front-line therapeutics for ischemic
      stroke.

PMID- 30284495
TI  - Graphene oxide-chloroquine nanoconjugate induce necroptotic death in A549 cancer
      cells through autophagy modulation.
AB  - AIM: Chloroquine (Chl) has shown its potential in cancer therapy and graphene
      oxide (GO) exhibited excellent tumor-targeting ability, biocompatibility and low
      toxicity. We have endeavored to conjugate Chl to GO sheets and investigated the
      nonproliferation action on A549 cell lines along with cell signaling pathways.
      MATERIALS & METHODS: Cellular toxicity, autophagic flux modulation and cell death
      mechanism induced by GO-Chl have been investigated on A549 cell lines. RESULTS &
      CONCLUSION: GO-Chl induces accumulation of autophagosomes (monodansylcadaverine
      staining, green fluorescence protein-tagged LC3 plasmid and transmission electron
      microscopy observations) in A549 cells through the blockade of autophagic flux
      that serves as scaffold for necrosome assembling and activates necroptotic cell
      death. GO-Chl nanoconjugate could be used as an effective cancer therapeutic
      agent, by targeting the autophagy necroptosis axis.

PMID- 30284497
TI  - CCL25 chemokine-guided stem cell attraction: an assessment of possible benefits
      and risks.
AB  - Due to its chemoattraction potential on mesenchymal stromal cells of the
      CCL25/CCR9 axis, local application of CCL25 to severely damaged tissues may be a
      promising approach for regenerative therapies. Analysis of the given data
      revealed that CCL25/CCR9 signaling has a crucial role in regulation of an adult
      immune homeostasis. CCR9 expression variations resulted in dysfunctional immune
      response in colitis, rheumatoid arthritis and endometriosis. Regarding oncology,
      different neoplastic tissues exploit CCL25-dependent CCR9 signaling for either
      local proliferation or migration processes. The CCR9 pathway likely can trigger
      crosstalk between the Akt and NOTCH pathway and thus participate in the
      regulation of the neoplastic behavior. In conclusion, the designated application
      tissue requires precise molecular analysis of possible CCR9 expression due to its
      proto-oncogenic characteristics.

PMID- 30284496
TI  - Kinetic analysis of push-up exercises: a systematic review with practical
      recommendations.
AB  - Push-ups represent one of the simplest and most popular strengthening exercise.
      The aim of this study was to systematically review and critically appraise the
      literature on the kinetics-related characteristics of different types of push
      ups, with the objective of optimising training prescription and exercise-related
      load. A systematic search was conducted in the electronic databases PubMed,
      Google Scholar and Science Direct up to April 2018. Studies that reported kinetic
      data (e.g. initial and peak-force supported by the upper-limbs, impact-force,
      peak-flexion-moment of the elbow-joint, rate of propulsive- and impact-, and
      vertebral-joint compressive-forces) related to push-ups and included trained,
      recreational and untrained participants, were considered. The risk of bias in the
      included studies was assessed using the Critical Appraisal Skills Programme
      scale. From 5290 articles retrieved in the initial search, only 26 studies were
      included in this review. Kinetic data for 46 push-up variants were assessed. A
      limitation of the current review is that the relationship between our findings
      and actual clinical or practical consequences is not statistically proven but can
      only be inferred from our critical descriptive approach. Overall, this review
      provides detailed data on specific characteristics and intensities of push-up
      variations, in order to optimise exercise prescription for training and
      rehabilitation purposes.

PMID- 30284498
TI  - Safety considerations for nanoparticles in tumor treatment.

PMID- 30284499
TI  - Health-Related Beliefs, Practices, and Experiences of Migrant Dominicans in the
      Northeastern United States.
AB  - INTRODUCTION: The purpose of this study was to describe cultural health beliefs,
      practices, and experiences with professional health care in the United States by
      migrants from the Dominican Republic because their practices are largely unknown
      to professional providers. METHOD: A qualitative descriptive design was used,
      guided by Leininger's culture care theory and four-phase analysis method with a
      convenience sample of 15 self-identified migrant Dominican adults in three
      interpreter-assisted focus groups, in a familiar apartment. RESULTS: The
      following four themes emerged: Stress affects health and well-being, family
      support and faith in God are essential, use of folk care and professional care to
      treat illness and maintain health, and access to care, cost, communication and
      expressions of caring practices affect perceptions about the quality of
      professional care. DISCUSSION: Results informed development of specific
      strategies to provide culturally responsive care and risk-reduction interventions
      that promote health and improve quality of care in the Dominican community.

PMID- 30284500
TI  - Life in the Balance: Are Women's Possible Selves Constrained by Men's Domestic
      Involvement?
AB  - Do young women's expectations about potential romantic partners' likelihood of
      adopting caregiving roles in the future contribute to whether they imagine
      themselves in nontraditional future roles? Meta-analyzed effect sizes of five
      experiments (total N = 645) supported this complementarity hypothesis. Women who
      were primed with family-focused (vs. career-focused) male exemplars (Preliminary
      Study) or information that men are rapidly (vs. slowly) assuming greater
      caregiving responsibilities (Studies 1-4) were more likely to envision becoming
      the primary economic provider and less likely to envision becoming the primary
      caregiver of their future families. A meta-analysis across studies revealed that
      gender role complementarity has a small-to-medium effect on both women's abstract
      expectations of becoming the primary economic provider ( d = .27) and the primary
      caregiver ( d = -.26). These patterns suggest that women's stereotypes about
      men's stagnant or changing gender roles might subtly constrain women's own
      expected work and family roles.

PMID- 30284501
TI  - Dyadic interventions to promote physical activity and reduce sedentary behaviour:
      systematic review and meta-analysis.
AB  - Several interventions have targeted dyads to promote physical activity (PA) or
      reduce sedentary behaviour (SB), but the evidence has not been synthesised. Sixty
      nine studies were identified from MEDLINE, PsycINFO, and Web of Science, and 59
      were included in the main meta-analyses (providing 72 independent tests).
      Intervention details, type of dyadic goal, participant characteristics, and
      methodological quality were extracted and their impact on the overall effect size
      was examined. Sensitivity analyses tested effect robustness to (a) the effects of
      other statistically significant moderators; (b) outliers; (c) data included for
      participants who were not the main target of the intervention. Dyadic
      interventions had a small positive, highly heterogeneous, effect on PA g = .203,
      95% CI [0.123-0.282], compared to comparison conditions including equivalent
      interventions targeting individuals. Shared target-oriented goals (where both
      dyad members hold the same PA goal for the main target of the intervention) and
      peer/friend dyads were associated with larger effect sizes across most analyses.
      Dyadic interventions produced a small homogeneous reduction in SB. Given dyadic
      interventions promote PA over-and-above equivalent interventions targeting
      individuals, these interventions should be more widespread. However, moderating
      factors such as the types of PA goal and dyad need to be considered to maximise
      effects.

PMID- 30284502
TI  - Mesoporous silica-coated bismuth nanohybrids as a new platform for
      photoacoustic/computed tomography imaging and synergistic chemophotothermal
      therapy.
AB  - AIM: Polyethylene glycol modified mesoporous silica-coated bismuth nanohybrids
      (Bi@mSiO2-PEG) are fabricated for chemothermotherapy and multimodal imaging.
      MATERIALS & METHODS: The Bi@mSiO2-PEG are synthesized by coating mesoporous SiO2
      onto metallic Bi cores, followed by PEG modification. Their cytotoxicity,
      photothermal effect, drug loading, antitumor effect and imaging abilities are
      evaluated. RESULTS: The nanohybrids show good biocompatibility, strong near
      infrared absorbance, high photothermal conversion efficiency (~36.6%), prominent
      infrared thermal imaging and photothermal killing efficacy on cancer cells.
      Utilizing the nanohybrids as potent drug carriers, a synergistic antitumor effect
      through chemothermotherapy is realized. Thanks to the superhigh x-ray attenuation
      coefficient and strong photothermal ability, high-contrast photoacoustic and x
      ray computed tomography imaging are achieved. CONCLUSION: These results reveal
      great potentials of the Bi@mSiO2-PEG for precise and efficient anticancer
      treatments.

PMID- 30284503
TI  - The intergroup empathy bias among incoming medical students.
AB  - BACKGROUND: Previous studies revealed a significant empathy decline over time
      among medical students. Scientific literature also supports the influence of
      group belonging on the empathy expression. OBJECTIVE: Through this study, we
      aimed to demonstrate whether group belonging (peers or patients) significantly
      influences empathy levels before students undertake their education in medicine.
      DESIGN: A total of 194 incoming medical students participated in our study. All
      participants filled-in the Interpersonal Reactivity Index under three primed
      situations (a general; a peers' one; a patients' one) at three different points
      in time during a session of information. RESULTS: Analyses revealed significant
      main effects of: gender; situations; and empathy dimensions. We also obtained a
      significant interaction effect between dimensions and situations. CONCLUSIONS: We
      showed that empathy levels were modulated by group belonging (25% of the variance
      was explained by group belonging). Post hoc analyses showed that the differences
      between the peers' and patients' situations tend to reveal an appropriate
      professional attitude with regard to patients because they displayed: (1) lower
      scores on personal distress and fantasy; (2) higher scores on perspective taking
      (as for peers); (3) stable scores on empathic concern in peers' and patients'
      situations. However, integrating empathy lessons in the educational program of
      medical students remains a priority. In a long-term perspective, these findings
      suggest an investigation of the impacts of group belonging on the evolution of
      students' empathy scores through their medicine studies.

PMID- 30284504
TI  - Structural insight into antisense gapmer-RNA oligomer duplexes through molecular
      dynamics simulations.
AB  - There is an extensive research carrying out on antisense technology and the
      molecules entering into clinical trials are increasing rapidly. Phosphorothioate
      (PS) is a chemical modification in which nonbridged oxygen is replaced with a
      sulfur, consequently providing resistance against nuclease activity. The 2'-4'
      conformationally restricted nucleoside has the structural features of both 2'-O
      methoxy ethyl RNA (MOE), which shows good toxicity profile, and locked nucleic
      acid (LNA), which shows good binding affinity towards the target RNA. These
      modifications have been studied and suggested that they can be a potential
      therapeutic agents in antisense therapy. Mipomersen (ISIS 301012), which contains
      the novel nucleoside modification has been used to target to apolipoprotein (Apo
      B), which reduces LDL cholesterol by 6-41%. In this study, classical molecular
      dynamics (MD) simulations were performed on six different antisense gapmer/target
      RNA oligomer duplexes (LNA-PS-LNA/RNA, RcMOE-PS-RcMOE/RNA, ScMOE-PS-ScMOE/RNA,
      MOE-PS-MOE/RNA, PS-DNA/RNA and DNA/RNA) to investigate the structural dynamics,
      stability and solvation properties. The LNA, MOE nucleotides present in
      respective duplexes are showing the structure of A-form and the PS-DNA
      nucleotides resemble the structure of B-form helix with respect to some of the
      helical parameters. Free energy calculations suggest that the oligomer, which
      contains LNA binds to the RNA strongly than other modifications as shown in
      experimental results. The MOE modified nucleotide, which although had a lower
      binding affinity but higher solvent accessible surface area (SASA) compared to
      the other modifications, may be influencing the toxicity and hence may be used it
      in Mipomersen, the second antisense molecule which is approved by FDA.
      Communicated by Ramaswamy H. Sarma.

PMID- 30284505
TI  - Effects of sample handling on the detection of porcine reproductive and
      respiratory syndrome virus in oral fluids by reverse-transcription real-time PCR.
AB  - We evaluated effects of handling procedures on detection of porcine reproductive
      and respiratory syndrome virus (PRRSV) in oral fluids (OFs) by reverse
      transcription real-time PCR (RT-rtPCR). The experiments were conducted using a
      composite sample of PRRSV-positive OF collected from 5-wk-old pigs vaccinated 15
      d earlier with a modified-live PRRSV vaccine. Five pre-extraction sample-handling
      steps and all combinations thereof were evaluated: 1) thaw temperature (4 degrees
      C or 25 degrees C); 2) sample diluent (1:1 dilution with nuclease-free water or
      guanidinium thiocyanate-phenol); 3a) sonication of the sample (yes or no); 3b)
      temperature (4 degrees C or 25 degrees C) at which step 3a was conducted; and 4)
      temperature at which the sample was maintained after step 3b and until RNA
      extraction was initiated (4 degrees C or 25 degrees C). All combinations of the 5
      sample-handling steps (i.e., 32 unique treatments) were tested in a completely
      randomized factorial design with 4 replicates and 1 negative control for each
      treatment. The entire experiment was repeated on 5 separate days to produce a
      total of 800 PRRSV RT-rtPCR results. Binary (positive or negative) data were
      analyzed by logistic regression and results (Ct) were analyzed using a
      generalized linear model. Overall, 1 false-positive result was observed among 160
      negative controls (99.4% specificity), and 85 false-negative results were
      observed among the 640 known-positive samples (86.7% sensitivity). The most
      significant factor affecting test outcome was thaw temperature (4 degrees C or 25
      degrees C); samples thawed at 4 degrees C had higher positivity rate (94% vs.
      80%, p < 0.0001) and lower Ct (36.2 vs. 37.5, p < 0.0001).

PMID- 30284506
TI  - Intervention-Induced Motor Cortex Plasticity in Hemiparetic Children With
      Perinatal Stroke.
AB  - BACKGROUND: Clinical trials are suggesting efficacy of intensive therapy combined
      with brain stimulation to improve hand function in hemiparetic children with
      perinatal stroke. However, individual variability exists and the underlying
      neuroplasticity mechanisms are unknown. Exploring primary motor cortex (M1)
      neurophysiology, and how it changes with such interventions, may provide valuable
      biomarkers for advancing personalized neurorehabilitation. METHODS: Forty-five
      children (age 6-19 years) with hemiparesis participated in PLASTIC CHAMPS, a
      blinded, sham-controlled, factorial clinical trial. All received 80 hours of goal
      directed intensive upper extremity therapy. They were randomized into 4 groups:
      repetitive transcranial magnetic stimulation (rTMS) of contralesional M1,
      constraint therapy, both, or neither. Stimulus recruitment curves (SRC), short
      interval intracortical inhibition (SICI), and intracortical facilitation (ICF)
      for lesioned and contralesional M1 were investigated using TMS. Clinical
      assessments including the Assisting Hand Assessment (AHA) and Canadian
      Occupational Performance Measure (COPM) were conducted pre- and postintervention.
      RESULTS: All children completed the intervention and both function (AHA) and goal
      performance (COPM) improved with additive effects of rTMS and constraint ( P <
      .01). After intervention, motor-evoked potential (MEP) amplitudes from the
      contralesional M1 to the less-affected hand increased (n = 16, P < .02). SRC from
      the contralesional M1 to the less-affected hand increased (n = 25, P < .01). SICI
      of the contralesional M1 to the less-affected hand decreased (n = 30, P < .04).
      No changes were observed for ICF in either hemisphere ( P > .12). CONCLUSION: TMS
      applied before/after intensive neuromodulation therapies can explore M1
      neurophysiology and plasticity in children with cerebral palsy. Increased MEP
      sizes and decreased SICI may reflect mechanisms of interventional plasticity and
      be potential biomarkers of individualized medicine.

PMID- 30284507
TI  - EXPRESS: Gremlin1 blocks vascular endothelial growth factor signalling in the
      pulmonary microvascular endothelium.

PMID- 30284508
TI  - Are anticoagulants still indicated in pulmonary arterial hypertension?
AB  - Pulmonary arterial hypertension (PAH) is a type of pulmonary hypertension that is
      a progressive, fatal disease. Multiple underlying mechanisms for PAH have been
      identified, including vasoconstriction, intimal proliferation, medial
      hypertrophy, inflammation, mitochondrial dysfunction, and in situ thrombosis.
      Because it is an uncommon disease, it has been challenging to identify a specific
      treatment that targets the dominant disease mechanism in a given patient. Early
      success demonstrating that some patients (approximately 10%) possess pulmonary
      vasoreactivity at diagnosis has driven the development of pulmonary vasodilators
      as the mainstay of treatment. However, while they improve exercise tolerance in
      clinical trials, their effect on survival is limited. Therapies that target
      underlying disease mechanisms that affect a majority of patients are clearly
      needed if we are to significantly improve overall survival. In the actual
      guidelines, chronic anticoagulation is no longer recommended in patients with
      idiopathic, hereditary, and drug-induced PAH although there is much indirect
      evidence for this. There are data from over 40 years which include: (1) pathology
      studies showing the presence of thrombotic lesions in a majority of patients with
      PAH, both idiopathic and associated with many other conditions; (2) a similar
      frequency of thrombotic lesions in patients treated with pulmonary vasodilators
      as was seen in the years before their use; (3) mechanistic studies showing that
      procoagulant conditions predispose to the development of intraluminal thrombosis
      that contributes to vascular remodeling and the progressive nature of the
      pathologic changes; and (4) observational studies that, with one exception, have
      demonstrated a substantial survival advantage in patients with PAH treated with
      oral anticoagulation. Acknowledging that no prospective randomized trial with
      anticoagulants has ever been done, we recommend a pragmatic approach to the use
      of anticoagulants in PAH. We suggest that the risks and benefits of chronic
      anticoagulation be considered in individual patients, and that warfarin be
      prescribed in patients with PAH, unless they have an increased risk of bleeding.
      The question of whether direct oral anticoagulants (DOACs) would provide the same
      benefit as vitamin K antagonists is valid, but presently there are no data at all
      regarding their use in PAH. However, in patients with PAH in whom warfarin
      anticoagulation management proves problematic, it is reasonable to switch the
      patient to a DOAC as is current practice for other conditions.

PMID- 30284510
TI  - Nonionic but water soluble, [Glycine-Pd-Alanine] and [Glycine-Pd-Valine]
      complexes. Their synthesis, characterization, antitumor activities and rich
      DNA/HSA interaction studies.
AB  - Two novel, neutral and water soluble Pd(II) complexes of formula [Pd(Gly)(Ala)]
      (1) and [Pd(Gly)(Val)] (2) (Gly, Ala, and Val are anionic forms of glycine,
      alanine, and valine amino acids, respectively) have been synthesized and
      characterized by FT-IR, UV-Vis, 1H-NMR, elemental analysis, and molar
      conductivity measurement. The data revealed that each amino acid binds to Pd(II)
      through the nitrogen of -NH2 and the oxygen of -COO- groups and acts as a
      bidentate chelate. These complexes have been assayed against leukemia cells
      (K562) using MTT method. The results indicated that both of the complexes display
      more cytotoxicity than the well-known anticancer drug, cisplatin. The interaction
      of the compounds with calf thymus DNA (CT-DNA) and human serum albumin (HSA) were
      assayed by a series of experimental techniques including electronic absorption,
      fluorescence, viscometry, gel electrophoresis, and FT-IR. The results indicated
      that the two complexes have interesting binding propensities toward CT-DNA as
      well as HSA and the binding affinity of (1) is more than (2). The fluorescence
      data indicated that both complexes strongly quench the fluorescence of ethidium
      bromide-DNA system as well as the intrinsic fluorescence of HSA via static
      quenching procedures. The thermodynamic parameters (DeltaH degrees , DeltaS
      degrees , and DeltaG degrees ) calculated from the fluorescence studies showed
      that hydrogen bonds and van der Waals interactions play a major role in the
      binding of the complexes to DNA and HSA. We suggest that both of the Pd(II)
      complexes exhibit the groove binding mode with CT-DNA and interact with the main
      binding pocket of HSA. Communicated by Ramaswamy H. Sarma.

PMID- 30284509
TI  - Hypoxia-induced pulmonary vasoconstriction of intra-acinar arteries is impaired
      in NADPH oxidase 4 gene-deficient mice.
AB  - We show that genetic deficiency of the reactive oxygen species generating enzyme
      NADPH oxidase 4 (NOX4) impairs hypoxic pulmonary vasoconstriction in small (25-40
      um) intra-acinar, but not pre-acinar, arteries in murine precision cut lung
      slices. These data suggest an involvement of NOX4 in ventilation-perfusion
      matching at the acinar level.

PMID- 30284511
TI  - The development of medical MOOCs in China: current situation and challenges.
AB  - This study aimed to investigate the current situation and challenges on the
      development of medical massive open online courses (MOOCs) in China. A survey was
      constructed and the statistical analysis was adopted to evaluate the medical
      MOOCs. The results showed that the medical MOOC-related journal papers,
      conference papers, books and dissertations have risen dramatically over the past
      five years. In addition, the top 6 most representative MOOC platforms provide the
      majority (87%) of medical courses. The statistical analysis showed that PMPH-MOOC
      was the most influential medical MOOC platform in China. Compared to the foreign
      medical MOOCs, medical MOOCs in China were urgently in need of systemic planning,
      interaction activities and international certification. Overall, the findings
      suggest that the development of medical MOOCs for higher education has been
      achieved a great success along with a huge challenge.

PMID- 30284512
TI  - Retropharyngeal abscess as a paradoxical reaction in a child with multi-drug
      resistant tuberculosis.
AB  - Paradoxical reactions (PRs) are exaggerated inflammatory responses owing to
      recovery of cellular immunity following initiation of anti-tuberculous therapy
      (ATT). The presentation is worsening of pre-existing symptoms or development of
      new lesions. A 14-year-old girl with multi-drug-resistant tuberculosis developed
      a recurrent asymptomatic retropharyngeal abscess while on ATT. She required
      multiple aspirations of the abscess. Xpert MTB/RIF detected Mycobacterium
      tuberculosis from the aspirate which was resistant to rifampicin; culture was
      negative. Following aspirations of the abscess, continued ATT and a 2-month
      course of corticosteroids, she remains well and has gained weight. A
      retropharyngeal abscess presenting in the form of a PR has not been reported
      previously in adults or children.

PMID- 30284513
TI  - A plug and play approach for the decoration of nanoparticles with recombinant
      proteins.

PMID- 30284516
TI  - A comparative study of cybersickness during exposure to virtual reality and
      "classic" motion sickness: are they different?
AB  - Existing evidence suggest that cybersickness may be clinically different from
      "classic", motion-induced motion sickness; this evidence was however obtained in
      separate studies that focussed on just one of the two conditions. Our aim was to
      bring clarity to this issue, by directly comparing subjective symptoms and
      physiological effects of motion sickness induced by physical motion (Coriolis
      cross-coupling) and by immersion in virtual reality (ride on a roller coaster) in
      the same subjects. A cohort of 30 young healthy volunteers was exposed to both
      stimulations in a counter-balance order on two separate days at least one week
      apart. Nausea scores were recorded during the exposure, and Motion Sickness
      Assessment Questionnaire (MSAQ) was used to profile subjective symptoms post
      experiment. Tonic and phasic forehead skin conductance level (SCL) was measured
      before and during exposure in both stimulation methods. We found that nausea
      onset times and maximum nausea ratings were significantly correlated during both
      provocations (r=0.40, p=0.03 and r=0.56, p=0.0012, respectively). Symptom
      profiling with the MSAQ revealed substantial and significant correlations between
      total symptom scores (r=0.69, p<0.0001), between each of four symptom clusters
      and between 15/18 individual symptoms assessed in both conditions. Both
      provocations caused increase in tonic SCL associated with nausea, with a close
      correlation between the conditions (r=0.48, p=0.04). This was accompanied by a
      significant increase in the amplitude of phasic skin conductance transients in
      both experiments. We conclude that symptoms and physiological changes occurring
      during cybersickness and "classical" motion sickness are quite similar, at least
      during advanced stages of these malaises.

PMID- 30284517
TI  - Modelling mucosal surface roughness in the human velopharynx: a computational
      fluid dynamics study of healthy and obstructive sleep apnea airways.
AB  - : We previously published a unique methodology for quantifying human
      velopharyngeal mucosal surface topography and found increased mucosal surface
      roughness in obstructive sleep apnea (OSA) patients. In fluid mechanics, surface
      roughness is associated with increased frictional pressure losses and resistance.
      This study used computational fluid dynamics (CFD) to analyse the mechanistic
      effect of different levels of mucosal surface roughness on velopharyngeal
      airflow. METHODS: Reconstructed velopharyngeal models from OSA and Control
      subjects were modified, giving each model three levels of roughness, quantified
      by the curvature based surface roughness index (CBSRI0.6; range 24.8-68.6mm-1).
      CFD using the k-omega shear stress transport (SST) turbulence model was performed
      (unidirectional, inspiratory, steady state, 15l/min volumetric flow rate), and
      the effects of roughness on flow velocity, intraluminal pressure, wall shear
      stress and velopharyngeal resistance (Rv) were examined. RESULTS: Across all
      models, increasing roughness increased maximum flow velocity, wall shear stress
      and flow disruption, while decreasing intraluminal pressures. Linear mixed
      effects modelling demonstrated a log-linear relationship between CBSRI0.6 and Rv,
      with a common slope (log(Rv)/CBSRI0.6) of 0.0079 (95%CI 0.0015-0.0143; p=0.019)
      for all subjects, equating to a 1.9-fold increase in Rv when roughness increased
      from Control to OSA levels. At any fixed CBSRI0.6, the estimated difference in
      log(Rv) between OSA and Control models was 0.9382 (95%CI 0.0032-1.8732; p=0.049),
      equating to an 8.7-fold increase in Rv. CONCLUSION: This study supports the
      hypothesis that increasing mucosal surface roughness increases velopharyngeal
      airway resistance, particularly for anatomically narrower OSA airways, and may
      thus contribute to increased vulnerability to upper airway collapse in OSA
      patients.

PMID- 30284518
TI  - Arterial Blood Sampling in Male CD-1 and C57BL/6J Mice with 1% Isoflurane is
      Similar to Awake Mice.
AB  - Isoflurane (ISO) is a commonly used anesthetic that offers rapid recovery for
      laboratory animal research. Initial studies indicated no difference in PaCO2 or
      pH between conscious (NO ISO) and 1% ISO exposed CD-1 mice. Our laboratory
      investigated if arterial blood sampling with 1% ISO is a suitable alternative to
      NO ISO sampling for monitoring ventilation in a commonly studied mouse strain. We
      hypothesized similar blood chemistry, breathing patterns and cardiovascular
      responses with NO ISO and 1% ISO. C57BL/6J mice underwent unrestrained barometric
      plethysmography to quantify the pattern of breathing. Mice exposed to hypoxic and
      hypercapnic gas under 1% ISO displayed blunted responses; with air there were no
      breathing differences. Blood pressure and heart rate were not different between
      NO ISO and 1% ISO exposed mice breathing air. Oxygen saturation was not different
      between groups receiving 2% ISO, 1% ISO, or air. Breathing frequency stabilized
      at ~11 minutes of 1% ISO following 2% ISO exposure, suggesting that 11 minutes is
      the optimal time for a sample in C57BL/6J mice. Blood samples at 1% ISO and NO
      ISO revealed no differences in blood pH and PaCO2 in C57BL/6J mice. Overall, this
      method reveals similar arterial blood sampling values in awake and 1% ISO CD-1
      and C57BL/6J mice exposed to air. While this protocol may be appropriate in other
      mouse strains when a conscious sample is not feasible, caution is warranted to
      first identify breathing frequency responses at 1% ISO to tailor the protocol.

PMID- 30284519
TI  - A nutrient cocktail prevents lipid metabolism alterations induced by 20 days of
      daily steps reduction and fructose overfeeding: Result from a randomized study.
AB  - CONTEXT: Physical inactivity and sedentary behaviours are independent risks
      factors for numerous diseases. OBJECTIVE: We examined the capacity of a nutrient
      cocktail composed of polyphenols, omega-3 fatty acids, vitamin E and selenium to
      prevent the expected metabolic alterations induced physical activity and
      sedentary behaviors. DESIGN/SETTING/PARTICIPANTS: Twenty healthy trained men
      (averaging~14,000 steps/d and engaged in sports) were randomly divided into a
      control group (no supplementation) and a cocktail group for a 20-day free-living
      intervention during which they stopped exercise and decreased their daily steps
      to averaging~3000. During the last 10 days metabolic changes were further
      triggered by fructose overfeeding. On days 0, 10 and 20 body composition (DXA),
      blood chemistry, glucose tolerance (OGTT) and substrate oxidation (indirect
      calorimetry) were measured. Glucose tolerance included 1% fructose labelled with
      (U-13C) fructose to assess liver de novo lipogenesis. Histological changes and
      related cellular markers were assessed from muscle biopsies collected on days 0
      and 20. RESULTS: While the cocktail did not prevent the decrease in insulin
      sensitivity and its muscular correlates induced by the intervention, it fully
      prevented the hypertriglyceridemia, the drop in fasting HDL and total fat
      oxidation, and the increase in de novo lipogenesis. The cocktail further
      prevented the decrease in type-IIa muscle fiber cross-sectional area and was
      associated with lower protein ubiquitination content. The circulating anti
      oxidant capacity was improved by the cocktail following the OGTT. CONCLUSION: A
      cocktail of nutrient compounds from dietary origin protects against the
      alterations in lipid metabolism induced by physical inactivity and fructose
      overfeeding.

PMID- 30284520
TI  - Transgenic overexpression of active HDAC4 in the heart attenuates cardiac
      function and exacerbates remodeling in infarcted myocardium.
AB  - Histone deacetylases (HDACs) play a critical role in modulating cardiac function
      and ischemic injury. HDAC4 was found to be elevated and activated in response to
      injury. However, whether HDAC4 mediates cardiac function is currently unknown. In
      this study, we created myocyte-specific activated HDAC4 transgenic mice to
      examine the role of HDAC4 in mediating cardiac function during development and
      response to infarction. There are no differences in cardiac function and gross
      phenotype between wild type and cardiomyocyte-specific HDAC4 transgenic mice at
      one month of age. However, cardiac dysfunction and vascular growth deficiency
      were displayed in six-month old HDAC4 transgenic mice as compared to wild type
      mice. Activation of HDAC4 increased heart and myocyte size, hypertrophic
      proteins, and interstitial fibrosis in six-month old mice, but not in one-month
      old mice. To further define whether activated HDAC4 in the heart could impact
      myocardial function and remodeling, myocardial infarction was created in both
      wild type and cardiomyocyte-specific HDAC4 transgenic mice. In myocardial
      infarction, the overexpression of activated HDAC4 exacerbated cardiac dysfunction
      and augmented cardiac remodeling and interstitial fibrosis, which was associated
      with the reduction of cardiokines in the heart. These results indicate the
      activation of HDAC4 as a crucial regulator for cardiac function in development
      and myocardial infarction.

PMID- 30284521
TI  - Disparities in rural-vs-urban achievement of millennium development goals in
      Cambodia: implications for current and future child health.
AB  - BACKGROUND: Cambodia has made significant economic, political, and health
      advancements with the implementation of the millennium development goals (MDG).
      Important gaps in child health still exist, however, and accurate assessments of
      lingering disparities within the country will be essential for meeting the
      Sustainable Development Goals by 2030. AIM: This investigation hypothesised that
      child-health improvements in rural areas of Cambodia continue to lag behind urban
      areas. The study objective was to identify specific disparities in rural
      achievement of MDG within Cambodia to direct future work in child health.
      METHODS: Surveys were conducted in 230 rural households in four villages in
      Kampot and Kampong Speu provinces to assess risk factors contributing to lack of
      village-level achievement of MDG. National urban and rural data were used for
      comparison. RESULTS: An under-5 death in the preceding year was reported by 11.5%
      (n = 26) of the households surveyed. Under-use of common public health
      interventions (vaccinations, clean drinking water, oral rehydration therapy,
      iodised salt, bed nets, antenatal care, and improved sanitation facilities) was
      observed in all villages. Under-use of the interventions was more common in rural
      than urban areas. CONCLUSION: Achievement of child-health-related MDG lags in
      rural areas of Cambodia. Child health risk factors varied widely among villages.
      Village-specific risk factors for which immediate action can be taken are a
      priority, particularly vaccination in Angkcheay and Takoa and clean drinking
      water in Pos Pong. Elimination of disparities in rural child health will
      ultimately require significant resource allocation in rural areas, e.g. improved
      sanitation facilities, piped water supply and sustained public health
      initiatives.

PMID- 30284522
TI  - Internal herniation through the foramen of Winslow: a case report.

PMID- 30284523
TI  - Challenging the assertion of comparability of surveillance and administrative
      data.

PMID- 30284524
TI  - Sink traps as the source of transmission of OXA-48-producing Serratia marcescens
      in an intensive care unit.
AB  - BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) outbreaks are mostly
      attributed to patient-to-patient transmission via healthcare workers. OBJECTIVE:
      We describe successful containment of a prolonged OXA-48-producing S. marcescens
      outbreak after recognizing the sink traps as the source of transmission. METHODS:
      The Sheba Medical Center intensive care unit (ICU), contains 16 single-bed, semi
      closed rooms. Active CPE surveillance includes twice-weekly rectal screening of
      all patients. A case was defined as a patient detected with OXA-48 CPE >72 hours
      after admission. A root-cause analysis was used to investigate the outbreak. All
      samples were inoculated on chrom-agar CRE, and carbapenemase genes were detected
      using commercial molecular Xpert-Carba-R. Environmental and patient S. marcescens
      isolates were characterized using PFGE. RESULTS: From January 2016 to May 2017,
      32 OXA-48 CPE cases were detected, and 81% of these were S. marcescens. A single
      clone was the cause of all but the first 2 cases. The common factor in all cases
      was the use of relatively large amounts of tap water. The outbreak clone was
      detected in 2 sink outlets and 16 sink traps. In addition to routine strict
      infection control measures, measures taken to contain the outbreak included (1)
      various sink decontamination efforts, which eliminated the bacteria from the sink
      drains only temporarily and (2) educational intervention that engaged the ICU
      team and lead to high adherence to 'sink-contamination prevention guidelines.' No
      additional cases were detected for 12 months. CONCLUSIONS: Despite persistence of
      the outbreak clones in the environmental reservoir for 1 year, the outbreak was
      rapidly and successfully contained. Addressing sink traps as hidden reservoirs
      played a major role in the intervention.

PMID- 30284525
TI  - Repeated Chlamydia trachomatis infections are associated with lower bacterial
      loads.
AB  - Chlamydia trachomatis (CT) infections remain highly prevalent. CT reinfection
      occurs frequently within months after treatment, likely contributing to
      sustaining the high CT infection prevalence. Sparse studies have suggested CT
      reinfection is associated with a lower organism load, but it is unclear whether
      CT load at the time of treatment influences CT reinfection risk. In this study,
      women presenting for treatment of a positive CT screening test were enrolled,
      treated and returned for 3- and 6-month follow-up visits. CT organism loads were
      quantified at each visit. We evaluated for an association of CT bacterial load at
      initial infection with reinfection risk and investigated factors influencing the
      CT load at baseline and follow-up in those with CT reinfection. We found no
      association of initial CT load with reinfection risk. We found a significant
      decrease in the median log10 CT load from baseline to follow-up in those with
      reinfection (5.6 CT/ml vs. 4.5 CT/ml; P = 0.015). Upon stratification of
      reinfected subjects based upon presence or absence of a history of CT infections
      prior to their infection at the baseline visit, we found a significant decline in
      the CT load from baseline to follow-up (5.7 CT/ml vs. 4.3 CT/ml; P = 0.021)
      exclusively in patients with a history of CT infections prior to our study. Our
      findings suggest repeated CT infections may lead to possible development of
      partial immunity against CT.

PMID- 30284526
TI  - Optimising amino acid absorption: essential to improve nitrogen balance and
      metabolic control in phenylketonuria.
AB  - It has been nearly 70 years since the discovery that strict adherence to a diet
      low in phenylalanine prevents severe neurological sequelae in patients with
      phenylalanine hydroxylase deficiency (phenylketonuria; PKU). Today, dietary
      treatment with restricted phenylalanine intake supplemented with non
      phenylalanine amino acids to support growth and maintain a healthy body
      composition remains the mainstay of therapy. However, a better understanding is
      needed of the factors that influence N balance in the context of amino acid
      supplementation. The aim of the present paper is to summarise considerations for
      improving N balance in patients with PKU, with a focus on gaining greater
      understanding of amino acid absorption, disposition and utilisation. In addition,
      the impact of phenylalanine-free amino acids on 24 h blood phenylalanine/tyrosine
      circadian rhythm is evaluated. We compare the effects of administering intact
      protein v. free amino acid on protein metabolism and discuss the possibility of
      improving outcomes by administering amino acid mixtures so that their absorption
      profile mimics that of intact protein. Protein substitutes with the ability to
      delay absorption of phenylalanine and tyrosine, mimicking physiological
      absorption kinetics, are expected to improve the rate of assimilation into
      protein and minimise fluctuations in quantitative plasma amino acid levels. They
      may also help maintain normal glycaemia and satiety sensation. This is likely to
      play an important role in improving the management of patients with PKU.

PMID- 30284527
TI  - Advancing the assessment of cultural orientation: A developmental and contextual
      framework of multiple psychological dimensions and social identities.
AB  - This paper aims to advance the scientific understanding of the role of culture,
      particularly cultural orientation, in development and psychopathology. We advance
      a theoretical framework that conceptualizes cultural orientation as a
      developmental construct represented by multiple psychological dimensions and
      social identities, and influenced by the contexts in which individuals are
      embedded. This perspective suggests that cultural orientation changes within
      individuals over time as a function of their experiences with and memberships in
      multiple groups, including the mainstream and ethnic culture groups, as well as a
      function of their normative developmental changes (i.e., the development of
      cognitive, social, and emotional capabilities). In addition, this framework
      places the development of an ethnic culture social identity (e.g., an ethnic
      identity) and a mainstream culture social identity in broader developmental
      perspectives that recognize these as two of the many social identities that are
      simultaneously embedded within the individual's self-concept and that
      simultaneously influence one's cultural orientation. To support the successful
      integration of culture into the study of development and psychopathology, we
      describe how highly reliable and valid measures of cultural orientation, indexed
      by individuals' social identities, are essential for generating a scientifically
      credible understanding of the role of cultural orientation in development and
      psychopathology. Further, we detail some best research practices associated with
      our developmental and contextual framework, and note some important
      considerations for researchers interested in studying cultural orientation,
      development, and psychopathology.

PMID- 30284528
TI  - Identifying the Underlying Mechanisms of Change During Acceptance and Commitment
      Therapy (ACT): A Systematic Review of Contemporary Mediation Studies.
AB  - BACKGROUND: Mediation studies test the mechanisms by which interventions produce
      clinical outcomes. Consistent positive mediation results have previously been
      evidenced (Hayes et al., 2006) for the putative processes that compromise the
      psychological flexibility model of acceptance and commitment therapy (ACT). AIMS:
      The present review aimed to update and extend the ACT mediation evidence base by
      reviewing mediation studies published since the review of Hayes et al. (2006).
      METHOD: ACT mediation studies published between 2006 and 2015 were systematically
      collated, synthesized and quality assessed. RESULTS: Twelve studies met inclusion
      criteria and findings were synthesized by (a) the putative processes under
      investigation, and (b) the outcomes on which processes were tested for mediation.
      Mediation results were found to be generally consistent with the psychological
      flexibility model of ACT. However, studies were limited in methodological quality
      and were overly focused on a small number of putative processes. CONCLUSIONS:
      Further research is required that addresses the identified methodological
      limitations and also examines currently under-researched putative processes.

PMID- 30284529
TI  - Interaction between environmental and familial affective risk impacts psychosis
      admixture in states of affective dysregulation.
AB  - BACKGROUND: Evidence suggests that cannabis use, childhood adversity, and
      urbanicity, in interaction with proxy measures of genetic risk, may facilitate
      onset of psychosis in the sense of early affective dysregulation becoming
      'complicated' by, first, attenuated psychosis and, eventually, full-blown
      psychotic symptoms. METHODS: Data were derived from three waves of the second
      Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). The impact of
      environmental risk factors (cannabis use, childhood adversity, and urbanicity)
      was analyzed across severity levels of psychopathology defined by the degree to
      which affective dysregulation was 'complicated' by low-grade psychotic
      experiences ('attenuated psychosis' - moderately severe) and, overt psychotic
      symptoms leading to help-seeking ('clinical psychosis' - most severe). Familial
      and non-familial strata were defined based on family history of (mostly)
      affective disorder and used as a proxy for genetic risk in models of family
      history * environmental risk interaction. RESULTS: In proxy gene-environment
      interaction analysis, childhood adversity and cannabis use, and to a lesser
      extent urbanicity, displayed greater-than-additive risk if there was also
      evidence of familial affective liability. In addition, the interaction contrast
      ratio grew progressively greater across severity levels of psychosis admixture
      (none, attenuated psychosis, clinical psychosis) complicating affective
      dysregulation. CONCLUSION: Known environmental risks interact with familial
      evidence of affective liability in driving the level of psychosis admixture in
      states of early affective dysregulation in the general population, constituting
      an affective pathway to psychosis. There is interest in decomposing family
      history of affective liability into the environmental and genetic components that
      underlie the interactions as shown here.

PMID- 30284530
TI  - Biology and life history of Lema praeusta (Fab.) (Coleoptera: Chrysomelidae), a
      biocontrol agent of two Commelinaceae weeds, Commelina benghalensis and Murdannia
      nudiflora.
AB  - We examined previous reports of Lema praeusta (Fab.) (Coleoptera: Chrysomelidae)
      as a minor pest of turmeric, eggplant, bottle gourd and pumpkin leaves, but no
      feeding damage by larvae and adults of L. praeusta were recorded by us on these
      leaves. We observed feeding by the larvae and adults of L. praeusta on ten
      species of Commelinaceae plants in no-choice tests. The biology, fecundity and
      life table parameters of L. praeusta on two Commelinaceae weeds, Commelina
      benghalensis L. and Murdannia nudiflora (L.) Brenan were determined under
      laboratory conditions (27 +/- 1 degrees C, 65 +/- 5% RH and 12L:12D). Total
      larval development times of L. praeusta were 6.36 +/- 0.07 and 7.28 +/- 0.11 days
      (mean +/- SE) on C. benghalensis and M. nudiflora, respectively. Adult females
      lived 106.25 +/- 1.17 and 77.65 +/- 0.91 days (mean +/- SE) on C. benghalensis
      and M. nudiflora, respectively. Each female laid 272.95 +/- 2.39 and 224 +/- 1.74
      eggs (mean +/- SE) during a lifetime on C. benghalensis and M. nudiflora,
      respectively. The net reproductive rate (Ro), intrinsic rate of increase (rm),
      generation time (Tc), doubling time (DT) and finite rate of increase (lambda)
      were 136.48, 0.14, 36.17, 5.10 and 1.41 on C. benghalensis, respectively, whereas
      Ro, rm, Tc, DT and lambda were 112, 0.20, 23.64, 3.47 and 1.51 on M. nudiflora,
      respectively, suggesting that L. praeusta could be a potential biocontrol agent
      against C. benghalensis and M. nudiflora in the fields of rice, maize, sorghum,
      soybean, mung bean, peanut and cotton.

PMID- 30284532
TI  - Abstracts for the 42nd Human Genetics Society of Australasia Annual Scientific
      Meeting Sydney, New South Wales August 4-7, 2018.

PMID- 30284531
TI  - Abstracts for the 42nd Human Genetics Society of Australasia Annual Scientific
      Meeting Sydney, New South Wales August 4-7, 2018.

PMID- 30284534
TI  - THG volume 21 issue 5 Cover and Back matter.

PMID- 30284533
TI  - THG volume 21 issue 5 Cover and Front matter.

PMID- 30284536
TI  - Transparent thermoplastic polyurethane air filters for efficient electrostatic
      capture of particulate matter pollutants.
AB  - Particulate matter (PM) air pollution has been established as a significant
      threat to public health and a destructive factor to the climate and eco-systems.
      In order to eliminate the effects of PM air pollution, various air filtering
      strategies based on electrospun nanofibers have recently been developed. However,
      to date, almost none of the existing nanofibers based air filters can meet the
      requirements of high-performance air PM filtering, including high PM removal
      efficiency, low resistance to airflow, and long service life, etc. For the first
      time, we report a fabrication process using the electrospinning method for air
      filters based on thermoplastic polyurethane (TPU) nanofibers. The average
      diameters of TPU nanofibers are tunable from 0.14 +/- 0.06 MUm to 0.82 +/- 0.22
      MUm by changing the TPU concentrations in polymeric solutions. The optimized TPU
      nanofibers based air filters demonstrate the attractive attributes of high PM2.5
      removal efficiency up to 98.92%, good optical transparency of ~60%, low pressure
      drop of ~10 Pa, high quality factor of 0.45 Pa-1, and long service life under the
      flow rate of 200 ml min-1, which is ground-breaking compared with the existing
      nanofibers based air filters. These TPU nanofibers based air filters, with the
      excellent filtration performance and light transmittance, will shed light on the
      future research of nanofibers for various filtration applications and greatly
      benefit the public health by reducing the effects of PM air pollution.

PMID- 30284535
TI  - A plant chitinase controls cortical infection thread progression and nitrogen
      fixing symbiosis.
AB  - Morphogens provide positional information and their concentration is key to the
      organized development of multicellular organisms. Nitrogen-fixing root nodules
      are unique organs induced by Nod factor-producing bacteria. Localized production
      of Nod factors establishes a developmental field within the root where plant
      cells are reprogrammed to form infection threads and primordia. We found that
      regulation of Nod factor levels by Lotus japonicus is required for the formation
      of nitrogen-fixing organs, determining the fate of this induced developmental
      program. Our analysis of plant and bacterial mutants shows that a host chitinase
      modulates Nod factor levels possibly in a structure-dependent manner. In Lotus,
      this is required for maintaining Nod factor signalling in parallel with the
      elongation of infection threads within the nodule cortex, while root hair
      infection and primordia formation are not influenced. Our study shows that
      infected nodules require balanced levels of Nod factors for completing their
      transition to functional, nitrogen-fixing organs.

PMID- 30284537
TI  - Engineering of microscale vascularized fat that responds to perfusion with
      lipoactive hormones.
AB  - Current methods to treat large soft-tissue defects mainly rely on autologous
      transfer of adipocutaneous flaps, a method that is often limited by donor site
      availability. Engineered vascularized adipose tissues can potentially be a viable
      and readily accessible substitute to autologous flaps. In this study, we
      engineered a small-scale adipose tissue with pre-patterned vasculature that
      enables immediate perfusion. Vessels formed after one day of perfusion and
      displayed barrier function after three days of perfusion. Under constant
      perfusion, adipose tissues remained viable and responded to lipoactive hormones
      insulin and epinephrine with lipid accumulation and loss, respectively. Adipocyte
      growth correlated inversely with distance away from the feeding vessel, as
      predicted by a Krogh-type model.

PMID- 30284540
TI  - Co-axial wet-spinning in 3D bioprinting: state of the art and future perspective
      of microfluidic integration.
AB  - Nowadays, 3D bioprinting technologies are rapidly emerging in the field of tissue
      engineering and regenerative medicine as effective tools enabling the fabrication
      of advanced tissue constructs that can recapitulate in vitro organ/tissue
      functions. Selecting the best strategy for bioink deposition is often challenging
      and time consuming process, as bioink properties-in the first instance,
      rheological and gelation-strongly influence the suitable paradigms for its
      deposition. In this short review, we critically discuss one of the available
      approaches used for bioprinting-namely co-axial wet-spinning extrusion. Such a
      deposition system, in fact, demonstrated to be promising in terms of printing
      resolution, shape fidelity and versatility when compared to other methods. An
      overview of the performances of co-axial technology in the deposition of
      cellularized hydrogel fibres is discussed, highlighting its main features.
      Furthermore, we show how this approach allows (i) to decouple the printing
      accuracy from bioink rheological behaviour-thus notably simplifying the
      development of new bioinks-and (ii) to build heterogeneous multi-materials and/or
      multicellular constructs that can better mimic the native tissues when combined
      with microfluidic systems. Finally, the ongoing challenges and the future
      perspectives for the ultimate fabrication of functional constructs for advanced
      research studies are highlighted.

PMID- 30284539
TI  - Special issue on surfaces patterned by ion sputtering.

PMID- 30284538
TI  - Giant negative electrocaloric effect induced by domain transition in the strained
      ferroelectric thin film.
AB  - Electrocaloric effect (ECE) of ferroelectric materials is highly dependent on the
      domain transition with temperature. The effect of domain transition on the ECE of
      PbTiO3 (PTO) ferroelectric thin films subjected to different mismatch strains is
      investigated by a phase field model based on the time-dependent Ginzburg-Landau
      equation. The simulation results demonstrate that there exists a multiple-to
      single domain transition induced by temperature in the PTO thin film. The domain
      transition occurs at a temperature that is much lower than Curie temperature,
      resulting in a giant negative ECE in the strained ferroelectric thin film.
      Furthermore, the domain transition temperature and the corresponding negative ECE
      can be tuned by the magnitude of mismatch strain. The present study suggests an
      effective way to obtain a giant negative ECE by domain transitions in the
      strained ferroelectric thin film.

PMID- 30284541
TI  - The Convention on Human Rights and Biomedicine twenty years later: a look at the
      past and a step towards the future.
AB  - A document published by the Council of Europe provides practical indications for
      interpreting Article 21 of the Convention on Human Rights and Biomedicine, which
      asserts that "The human body and its parts shall not, as such, give rise to
      financial gain". In Italy the Istituto Superiore di Sanita (ISS, Italian National
      Institute of Health) is actively committed to comply fully with this imperative
      ethical requirement.

PMID- 30284542
TI  - Big Data. A briefing.
AB  - The data deluge (generally referred as "Big Data") biomedical scientists are
      facing in these years asks for a serious epistemological thinking in order to
      avoid both "data bases idolatry" and "preconceived refusal". Starting from the
      evident reproducibility crisis of biomedical sciences here we sketch some
      hopefully useful indications for a sensible use of data mining approaches.

PMID- 30284543
TI  - Proof of nicotine transfer to rat pups through maternal breast feeding to
      evaluate the neurobehavioral consequences of nicotine exposure.
AB  - This study investigates the transfer of nicotine from lactating dams to their
      offspring through breast milk, in the frame of a research focused to ascertain
      toxicological and neuro-behavioural effects on pups as consequence of either
      unavoidable ("yoked & forced") or voluntary ("freely-chosen") maternal nicotine
      exposure. To this aim, plasmatic concentrations of nicotine and cotinine were
      determined by LC-MS/MS in Wistar rat pups whose mothers were orally administered
      with nicotine during lactation. Mothers were divided into a voluntary drinking
      group, an unavoidable consumption group, and controls. The limits of detection
      and quantification of the LC-MS/MS method were 0.20 and 0.65 ng/mL, respectively.
      Within-laboratory reproducibility (CV%) was <12%, with recovery of 86.2-118.8%.
      Results showed the presence of nicotine in 67% of samples from freely-chosen
      consumption group (1.30 +/- 0.31 ng/mL) and in 60% of samples from yoked
      consumption group (1.19 +/- 0.62 ng/mL); cotinine was found in all the samples
      from freely-chosen (1.92 +/- 0.77 ng/mL) and yoked-consumption groups (1.43 +/-
      0.30 ng/mL). Data provide an evidence-based support to maternal/offspring
      nicotine transfer as function of different ways of oral exposure.

PMID- 30284544
TI  - The effect of the burden of caregiving for people with spinal cord injury (SCI):
      a cross-sectional study.
AB  - AIM: To assess the caregiver burden (CB) of caregivers for people with Spinal
      Cord Injury (SCI) and to examine the psychological impact of the burden of
      caregiving. MATERIALS AND METHODS: Cross-sectional study. A set of structured
      questionnaires was administered to 55 family caregivers of individuals with SCI.
      The Modified Barthel Index was used to evaluate the independence of care
      recipients. The Caregiver Burden Inventory was modified and used to assess the
      CB. The Family Strain Questionnaire - Short Form was administered to measure the
      psychological impact of CB. The Short Form 36 was used to assess the health
      status of the participants. RESULTS: CB affects mainly the domains related to
      time management, the physical condition of caregivers and their sense of personal
      failure. An increased level of CB and the dependency level of SCI survivors is
      significantly correlated (p < 0.01) with an increase in the need of psychological
      support and a decrease in perceived health and quality of life. CONCLUSIONS:
      Caregiving for people with SCI implies the occurrence of CB. The contribution of
      caregivers should be recognised and supported with tailored relief interventions.

PMID- 30284545
TI  - Pain prevalence, severity, assessment and management in hospitalized adult
      patients: a result of a multicenter cross sectional study.
AB  - INTRODUCTION: The measurement of pain prevalence among the patients admitted to
      hospital, estimated that pain remains a common problem for patients. METHODS:
      This is a multi-center cross sectional study carried out in Italian Hospitals,
      where data was collected in only one day. All patients aged at least 18 years,
      hospitalized able or unable to communicate, were eligible to be included in the
      study. Patients with curarization or quadriplegia (any cause) were excluded.
      RESULTS: Some hospitals and residential structures took part in our research, 26
      centers in total. Pain prevalence has been observed in 268 patients (38%) (95% CI
      = 34%-41%) (range within wards 31-47%). Women are at higher risk than men (RR =
      1.59, 95% CI = 1.29-1.95). Pain prevalence was more observed at 10.9 (+ 1.46)
      days after surgery. Severe pain has been observed in 148 (21.2%) cases. Pain was
      managed in 223 (83.2%) cases, and it was predominantly treated with the
      administration of paracetamol (n = 55; 24.7%) within 30 minutes after having
      ascertained the presence of pain. CONCLUSIONS: Pain is reported by about 4 out of
      10 adults, with a higher prevalence of cases in women, and its appearance does
      not depend on the care setting. In order to assess the prevalence of pain
      carefully, an Italian study that involves all regions and a large number of the
      centers may be necessary.

PMID- 30284546
TI  - Relationship between anatomical sites and severity of the lesions and use of
      alcohol and psychotropic substances in traumatized drivers admitted to the
      Emergency Department of Padua, Italy.
AB  - INTRODUCTION: Driving under the influence of alcohol and/or psychoactive
      substances increases the risk of road accidents, but it is controversial whether
      this affects site and severity of injuries. MATERIAL AND METHODS: We search for
      alcohol, cannabinoids, cocaine, benzodiazepines, opioids, methadone, amphetamines
      and barbiturates in biological fluids of 1764 traumatized drivers admitted to the
      Emergency Department (ED) of Padua between 2010 and 2014. RESULTS: We note
      correlation between alcohol and benzodiazepines and admission in ICU and between
      all the intoxications and the reserved prognosis. The sites of injuries were:
      head (37.13%), maxillofacial (8.33%), spinal column (44.67%), thoracic (15.31%),
      abdominal (5%), pelvic (2.55%) and limb traumas (23.58%). We observed a
      correlation between head trauma (p < 0.0001), maxillofacial trauma (p = 0.0418),
      thoracic trauma (p = 0.0215), pelvic trauma (p = 0.0008), spinal column trauma (p
      < 0.0001) and the totality of the intoxication and an association between
      benzodiazepines and thoracic and pelvic trauma. CONCLUSIONS: Alcohol and
      benzodiazepines intoxication increases the risk of reserved prognosis and
      admission in ICU; benzodiazepines intoxication correlates with thoracic and
      pelvic trauma.

PMID- 30284547
TI  - Medicine use and recurrent complaints among 15-years-old adolescents in Tuscany.
AB  - BACKGROUND: The use of medicines to treat common complaints, such as headache,
      stomachache, difficulty in getting to sleep and nervousness, is widespread among
      adolescents, and is increasing. The aim of this survey was to estimate the
      prevalence of recurrent specific complaints among 15-year-old adolescents in
      Tuscany over three years (2006, 2010 and 2014) and that of medicine use to treat
      these complaints among boys and girls. METHODS: The present study is based on
      data from the Tuscan HBSC studies at three time points (2006, 2010 and 2014),
      which involved 2830 adolescents, aged 15 years old (1395 boys and 1435 girls).
      RESULTS: Overall, the data confirm that adolescents who suffer from recurrent
      complaints are more likely to use medicines. The prevalence rates of all
      complaints were higher in girls than in boys in the three years considered. Over
      the whole period, headache, stomachache and difficulty in getting to sleep
      increased in girls, while boys displayed significant decrease in nervousness and
      stomachache. CONCLUSION: Our findings underline the fact that the use of
      medicines in adolescence is a public health concern and constitutes an emerging
      issue that needs greater attention and investigation on the part of scientific
      research.

PMID- 30284548
TI  - Assessment of health literacy skills in family doctors' patients by two brief,
      self-administered Italian measures.
AB  - Health Literacy (HL) is an important health determinant: low HL skills result in
      less healthy choices, riskier behavior, poorer health, less self-management and
      more hospitalization. An observational study was conducted in a selected
      population, attending the waiting rooms of family general practitioners, with the
      aim of assessing HL capabilities through the administration of two HL screeners
      (IMETER and SILS-IT), and comparing the two measures. An anonymous questionnaire
      was administered, consisting of the Italian versions of the two tests on a single
      sheet. Demographic data, as well as concomitant chronic diseases and vaccines
      received, were also collected. HL skills were measured by the scores observed at
      both tests, and by the frequency of subjects with low HL levels according to the
      respective cut-off values. Overall, 305 questionnaires were collected and
      analyzed. Regarding IMETER, the observed frequency of subjects with low HL skills
      was 25.2% and the mean score and mean adjusted-score (26.3 +/- 8.8 and 23.2 +/-
      9.4, respectively) were lower than those observed in previous studies. Similarly,
      at SILS-IT the percentage of subjects with low skills (49.9%) was higher than
      observed previously. IMETER showed high internal consistency (Cronbach's alpha >
      0.9). The two measures were significantly correlated, although with a low
      Spearman's coefficient, and IMETER did not provide significant information about
      the probability to predict low HL according to SILS-IT. These results are
      explainable by the differences in assessment and domains between the two tests,
      both reliable and suitable to screen patients with low functional HL.

PMID- 30284549
TI  - Epidemiology, surveillance and population screening of frailty. Results from the
      systematic reviews of the European Joint Action ADVANTAGE. Preface.

PMID- 30284550
TI  - Prevalence of frailty at population level in European ADVANTAGE Joint Action
      Member States: a systematic review and meta-analysis.
AB  - INTRODUCTION: Although frailty is common among community-dwelling older adults,
      its prevalence in Europe and how this varies between countries is unclear.
      METHODS: A systematic review and meta-analysis of literature on frailty
      prevalence in 22 European countries involved in the Joint Action ADVANTAGE was
      conducted. RESULTS: Sixty-two papers, representing 68 unique datasets were
      included. Meta-analysis showed an overall estimated frailty prevalence of 18%
      (95% confidence interval, CI, 15-21%). The prevalence in community (n = 53) vs
      non-community based studies (n = 15) was 12% (95% CI 10-15%) and 45% (95% CI 27
      63%), respectively. Pooled prevalence in community studies adopting a physical
      phenotype was 12% (95% CI 10-14%, n = 45) vs 16% (95% CI 7-29%, n = 8) for all
      other definitions. Sub-analysis of a subgroup of studies assessed as high-quality
      (n = 47) gave a pooled estimate of 17% (95% CI 13-21%). CONCLUSIONS: The
      considerable and significant heterogeneity found warrants the development of
      common methodological approaches to provide accurate and comparable frailty
      prevalence estimates at population-level.

PMID- 30284551
TI  - Incidence of frailty: a systematic review of scientific literature from a public
      health perspective.
AB  - INTRODUCTION: Because of the dynamic nature of frailty, prospective
      epidemiological data are essential to calibrate an adequate public health
      response. METHODS: A systematic review of literature on frailty incidence was
      conducted within the European Joint Action ADVANTAGE. RESULTS: Of the 6 studies
      included, only 3 were specifically aimed at estimating frailty incidence, and
      only 2 provided disaggregated results by at least gender. The mean follow-up
      length (1-22.2 years; median 5.1), sample size (74-6306 individuals), and age of
      participants (>= 30-65) varied greatly across studies. The adoption of incidence
      proportions rather than rates further limited comparability of results. After
      removing one outlier, incidence ranged from 5% (follow-up 22.2 years; age >= 30)
      to 13% (follow-up 1 year, age >= 55). CONCLUSIONS: Well-designed prospective
      studies of frailty are necessary. To facilitate comparison across studies and
      over time, incidence should be estimated in person-time rate. Analyses of factors
      associated with the development of frailty are needed to identify high-risk
      groups.

PMID- 30284552
TI  - Transitions and trajectories in frailty states over time: a systematic review of
      the European Joint Action ADVANTAGE.
AB  - INTRODUCTION: Frailty is a dynamic syndrome and may be reversible. Despite this,
      little is known about trajectories or transitions between different stages of
      frailty. METHODS: A systematic review was conducted, selecting studies reporting
      frailty trajectories or transition states for adults in any settings in European
      ADVANTAGE Joint Action Member States. RESULTS: Only three papers were included.
      Data were from longitudinal community-based cohorts in the United Kingdom,
      Netherlands and Italy. The English study investigated the effect of physical
      activity on the progression of frailty over a 10-year period. Two presented data
      on the proportion of participants experiencing at least one frailty transition
      over time (32.6% in the Italian sample aged >= 65 years followed for 4.4 years;
      34.3% in the Dutch sample aged 65-75 years, followed for 2 years). CONCLUSIONS:
      Data on frailty trajectories and transition states were limited and
      heterogeneous. Well-designed prospective studies and harmonized approaches to
      data collection are now needed.

PMID- 30284553
TI  - Population screening, monitoring and surveillance for frailty: three systematic
      reviews and a grey literature review.
AB  - INTRODUCTION: Little is known about programmes or interventions for the
      screening, monitoring and surveillance of frailty at population level. METHODS:
      Three systematic searches and an opportunistic grey literature review from the
      countries participating in the ADVANTAGE Joint Action were performed. RESULTS:
      Three studies reported local interventions to screen for frailty, two of them
      using a two-step screening and assessment method and one including monitoring
      activities. Another paper reviewed both providers' and participants' experiences
      of screening activities. Three on-going European projects and population
      screening programmes in primary care await evaluation. An electronic Frailty
      Index for use with patients' primary care records has been recently validated. No
      study described systematic processes for the surveillance of frailty.
      CONCLUSIONS: There is insufficient evidence for the effectiveness of population
      level screening, monitoring and surveillance of frailty. Development and
      evaluation of community-based two-step programmes including those that
      incorporate electronic health records, particularly in primary care, are now
      needed.

PMID- 30284554
TI  - Expression of Androgen Receptor Variant 7 (AR-V7) in Circulated Tumor Cells and
      Correlation with Drug Resistance of Prostate Cancer Cells.
AB  - BACKGROUND Prostate cancer is a common type of malignant tumor invading the male
      reproductive-urinary system, which has increasing incidence worldwide. Androgen
      receptor variant 7 (AR-V7) participates in regulating prostate cancer cell
      proliferation and gene expression. This study aimed to investigate the expression
      of AR-V7 in circulated tumor cells (CTCs) in patients with prostate cancer and to
      assess its correlation with drug sensitivity against enzalutamide or abiraterone.
      MATERIAL AND METHODS Blood samples of prostate cancer patients were collected for
      separating CTCs, in which mRNA expression level of full-length AR and AR-V7 was
      measured to analyze their correlation with enzalutamide or abiraterone
      resistance. Progression-free survival (PFS) of patients with different AR-V7
      expression levels was compared. AR-V7 was overexpressed in transfected prostate
      cancer cells, and its effects on proliferation were analyzed by clonal formation
      assay. RESULTS qRT-PCR showed AR-V7 overexpression in a total of 13 patients;
      76.92% of these patients developed drug resistance, the distal metastasis of
      which was significantly higher than that in the group with AR-V7 downregulation,
      with lower PFS (p<0.01). In cultured prostate cancer cells, AR-V7 upregulation
      resulted in a significantly higher clonal formation rate than in the control
      group with enzalutamide-containing medium (p<0.05). CONCLUSIONS In prostate
      cancer cells, AR-V7 expression is correlated with drug resistance, as AR-V7
      upregulation leads to enhanced proliferation potency of cancer cells, indicating
      unfavorable prognosis of patients.

PMID- 30284555
TI  - Social support in groups of mothers with different family status and its
      significance for satisfaction with work.
AB  - BACKGROUND: The purpose of the study was to determine to what degree social
      support is differentiated by family situation, with consideration of single
      motherhood as a difficult circumstance, and to establish if social support is
      significant for satisfaction with work in the studied group of mothers. MATERIAL
      AND METHODS: The sample consisted of 421 mothers: 206 (49%) of them were in a
      formal or casual relationship, and the remaining 215 (51%) were single mothers.
      The sample was studied by means of the <i>Berlin Social Support Scales</i>
      (BSSS), and the <i>Scale of Satisfaction with Work</i>. RESULTS: The results
      showed that single mothers perceived and obtained significantly less social
      support than mothers in relationships, and they offered to their relatives much
      more protective support (p = 0.006). Satisfaction with work among mothers -
      regardless of the family status - grows if the mother receives more social
      support. The information support received by mothers in relationships is not
      significantly related to satisfaction with work; seeking that type of support by
      single mothers does not have a meaningful relationship with satisfaction with
      work, either. Moreover, regardless of the mothers' family status, satisfaction
      with work is significantly differentiated by each type of social support, except
      for protective support. CONCLUSIONS: Social support is differentiated by the
      mothers' situation in the family and at work, and it has a different impact on
      single mothers from the impact on mothers in relationships. Med Pr 2018;69(5):497
      507.

PMID- 30284556
TI  - [Venous thromboembolism and atrial fibrillation in patients with cancer].

PMID- 30284557
TI  - [Treatment of cancer-associated venous thromboembolism].
AB  - Most clinical practice guidelines recommend low molecular weight heparin for the
      treatment of venous thromboembolism (VTE) in cancer patients. In the Hokusai VTE
      Cancer study, 1050 patients with cancer and acute VTE were randomized to oral
      edoxaban or subcutaneous dalteparin for at least 6 months and up to 12 months.
      Edoxaban was non-inferior to dalteparin with respect to the composite outcome of
      recurrent VTE and major bleeding. The rate of recurrent VTE was numerically
      lower, but the rate of major bleeding was significantly higher with edoxaban. The
      frequency of severe major bleeding was similar with edoxaban and dalteparin. The
      difference in major bleeding was mainly driven by a higher rate of upper
      gastrointestinal bleeding with edoxaban, especially in patients with
      gastrointestinal cancer. The pilot Select-D study randomized 406 patients with
      cancer and VTE to rivaroxaban or dalteparin for 6 months. Recurrent VTE was
      reduced, while both major and clinically relevant non major bleeding were
      significantly increased with rivaroxaban. Bleeding mostly involved the
      gastrointestinal tract and occurred in patients with gastroesophageal cancer.
      While waiting for ongoing studies on direct oral anticoagulants, the results of
      the Hokusai VTE Cancer suggest that edoxaban may represent a valuable alternative
      to low molecular weight heparin for the treatment of cancer-associated VTE. In
      patients with gastrointestinal cancer, the use of edoxaban requires careful
      benefit-risk weighting, taking into consideration patient's preferences.

PMID- 30284558
TI  - [Edoxaban in patients with atrial fibrillation and cancer].
AB  - Advances in cancer therapy have led to a significant improvement of survival in
      most types of malignancies over the past few decades. As a result, there is a
      growing population of cancer survivors, expected to reach 18 million people in
      2030 in the US and a similar number in Europe. Interestingly, cancer survivor
      studies have shown that although about half of these patients eventually die of
      cancer, one third of them actually die of cardiovascular disease. Arrhythmias
      represent a significant part of cardiovascular complications and atrial
      fibrillation is the main arrhythmia occurring in cancer patients.Antithrombotic
      therapy is a challenge: the optimal international normalized ratio (INR) level in
      patients on therapy with vitamin K antagonists is achieved in only 12% of them;
      in these patients, direct oral anticoagulants seem to be effective and safe for
      the prevention of stroke and systemic embolic events compared to warfarin and
      have similar risk of major bleeding. Among the trials, ENGAGE AF-TIMI 48 provides
      more data on the efficacy and safety of edoxaban in cancer patients.

PMID- 30284559
TI  - Correction to: Healthcare Experiences of Underrepresented Lesbian and Bisexual
      Women: A Focus Group Qualitative Study by LaVaccare S, Diamant AL, Friedman J,
      Singh KT, Baker JA, Rodriguez TA, Cohen SR, Dary FY, and Pregler J. Health Equity
      2018;2:131-138. DOI: 10.1089/heq.2017.0041.
AB  - [This corrects the article DOI: 10.1089/heq.2017.0041.].

PMID- 30284560
TI  - Infrared spectroscopy based on broadly tunable quantum cascade lasers and
      polycrystalline diamond waveguides.
AB  - Recently emerging broadly tunable quantum cascade lasers (tQCL) emitting in the
      mid-infrared (MIR) are a versatile alternative to well established thermal
      emitters in combination with interferometers as applied in Fourier transform
      infrared (FTIR) spectroscopy. The wide and highly spectrally resolved wavelength
      tuning characteristics along with superior spectral energy density renders laser
      based vibrational spectroscopy methods an efficient alternative vs. conventional
      molecular spectroscopies. Using diamond in attenuated total reflection (ATR)
      sensing formats benefits from the physical robustness and chemical resistivity of
      the internal reflective element (IRE) material. While inherent material
      absorption frequently limits the optical path length within diamond ATR elements,
      the herein presented design combining bright tQCLs with a multi-reflection
      polycrystalline diamond (PCD) ATR element enables an optical beam path length of
      approximately 5 cm. Thereby, sensitive spectroscopic measurements in the MIR are
      enabled. As an example, non-invasive glucose monitoring in human saliva is
      examined, highlighting the potential benefits of the proposed analytical concept
      with regards to exquisite sensitivity and selectivity in combination with a
      robust sensing interface, i.e., diamond. This approach paves the way towards
      directly analyzing molecular constituents in complex and potentially corrosive
      biomedical and biochemical matrices.

PMID- 30284571
TI  - Metal binding functions of metallothioneins in the slug Arion vulgaris differ
      from metal-specific isoforms of terrestrial snails.
AB  - Arion vulgaris is a land-living European slug belonging to the gastropod clade of
      Stylommatophora. The species is known as an efficient pest organism in vegetable
      gardening and horticulture, which may in part be the consequence of its
      genetically based innate immunity, along with its high ability to withstand toxic
      metal stress by intracellular detoxification. Like many species of terrestrial
      snails, slugs possess a distinct capacity for Cd accumulation in their midgut
      gland, where the metal is stored and inactivated, conferring to these animals an
      increased metal tolerance. Although midgut gland Cd fractions in slugs have been
      shown to be variably allocated between different metal-binding protein pools,
      depending on the level of environmental metal contamination, a true
      metallothionein (MT) was so far never characterized from slugs. Instead, the Cd
      binding proteins identified so far were described as Metallothionein-like
      proteins (MTLPs). In the present study, the slug A. vulgaris was used as a model
      organism, in order to verify the presence of true MTs in experimentally metal
      exposed slugs. We wanted to find out if these suggested slug MTs have similar
      metal binding properties and metal-selective features like those previously
      reported from helicid snails. To this aim, two MT isoform genes (AvMT1 and AvMT2)
      were characterized from midgut gland extracts and localized in the cells of this
      tissue. The AvMT1 and AvMT2 proteins were purified and partially sequenced, and
      their metal-binding features analysed after recombinant expression. Eventually,
      we wanted to understand if and by how much the metal binding features of the two
      MT isoforms of A. vulgaris may be related, owing to their reciprocal amino acid
      sequence similarities, to the binding properties of metal-specific MTs from
      terrestrial snails.

PMID- 30284572
TI  - Seven-coordinated iron(ii) spin-crossover molecules: some learning from iron
      substitution in [FexMn1-x(L222N3O2)(CN)2].H2O solid solutions.
AB  - The purpose of this work is to study the influence of the substitution of Fe(ii)
      by Mn(ii) on the spin crossover behaviour of [FexMn1-x(L222N3O2)(CN)2].H2O solid
      solutions where L222N3O2 is a macrocyclic ligand = 2,13-dimethyl-6,9-dioxa
      3,12,18-triazabicyclo[12.3.1]-octadeca-1(18),2,12,14,16-pentaene. The pure Fe(ii)
      complex is known to present a change of the coordination number from 7 at high
      temperature to 6 at low temperature. The target of the solid solution study was
      to investigate the effect of metal dilution on this coordination change. We have
      then measured the thermal spin crossover features as well as the metastable HS
      state lifetime generated by rapid thermal quenching, which was probed through the
      determination of the T(TIESST) value. A discussion of the spin-state as a
      function of temperature is given based on the phase diagram of this series and
      based on the investigation of the crystal structure of the
      [Mn(L222N3O2)(CN)2].H2O complex and its comparison with the published
      [Fe(L222N3O2)(CN)2].H2O master compound.

PMID- 30284573
TI  - Advances in organ-, body-, and disease-on-a-chip systems.

PMID- 30284574
TI  - Photoluminescence modulation of an atomically precise silver(i)-thiolate cluster
      via site-specific surface engineering.
AB  - A series of pyridyl ligand functionalized silver-thiolate nanoclusters with an
      identical cuboctahedron Ag12 core were prepared through site-specific surface
      engineering and fully characterized. Their wide-range photoluminescence
      modulation was systematically studied.

PMID- 30284575
TI  - Impact of composition and texture of protein-added yogurts on oral activity.
AB  - Understanding how oral processing is altered in response to changes in the
      composition and mechanical properties of food provides useful information to
      design food with improved satiating capacity which is largely influenced by oral
      exposure. In turn, this information deepens the knowledge about the physiology of
      texture perception. Six yogurts were formulated with different amounts of protein
      and protein sources and addition of apple cubes: control (C), extra skimmed milk
      powder-added (MP), whey protein isolate-added (WPI), and whey protein microgels
      added (WPM). In addition, MP was also added with maltodextrin (MPMD) and with
      fresh apple cubes (MPF). Activities of masseter, anterior temporalis and anterior
      digastric muscles during oral processing of each sample were recorded
      (electromyography), and jaw movement amplitudes in three dimensions were
      determined (jaw tracking system). The jaw muscle activities were highly dependent
      on the type of yogurt. Addition of apple cubes (MPF) almost doubled the oral
      processing time, number of chews, and muscle activity of all samples. MP and MPMD
      required similar but lower values of oral processing than MPF attributed to their
      reinforced network of milk protein. The lowest values were found for WPI, C and
      WPM, indicating a weaker, more fluid material. These behavioral results, which
      clearly differentiate the samples, are discussed in connection to the rheological
      and sensory properties of the yogurts. This study suggests that adding apple
      cubes significantly alters the oral processing pattern, such that they may be a
      more effective way of increasing the oral processing time (time exposure)
      compared to more subtle changes in the protein amount or source. Nevertheless,
      changes in the protein amount and source also affected, although to a lesser
      extent, the behavioral, rheological, and sensory properties of yogurt.

PMID- 30284576
TI  - Metallothioneins of the urochordate Oikopleura dioica have Cys-rich tandem
      repeats, large size and cadmium-binding preference.
AB  - The increasing levels of heavy metals derived from human activity are poisoning
      marine environments, threating zooplankton and ocean food webs. To protect
      themselves from the harmful effects of heavy metals, living beings have different
      physiological mechanisms, one of which is based on metallothioneins (MTs), a
      group of small cysteine-rich proteins that can bind heavy metals counteracting
      their toxicity. The MT system of urochordate appendicularians, an ecologically
      relevant component of the zooplankton, remained, however, unknown. In this work,
      we have characterized the MTs of the appendicularian species Oikopleura dioica,
      revealing that O. dioica has two MT genes, named OdMT1 and OdMT2, which encode
      for Cys-rich proteins, the former with 72 amino acids comparable with the small
      size MTs of other organisms, but the second with 399 amino acids representing the
      longest MT reported to date for any living being. Sequence analysis revealed that
      OdMT2 gene arose from a duplication of an ancestral OdMT1 gene followed by up to
      six tandem duplications of an ancestral repeat unit (RU) in the current OdMT2
      gene. Interestingly, each RU contained, in turn, an internal repeat of a 7-Cys
      subunit (X3CX3CX2CX2CX3-6CX2CXCX), which is repeated up to 12 times in OdMT2.
      Finally, ICP-AES analyses of heterologously expressed OdMT proteins showed that
      both MTs were capable to form metal-complexes, with preference for cadmium ions.
      Collectively, our results provide the first characterization of the MT system in
      an appendicularian species as an initial step to understand the zooplankton
      response to metal toxicity and other environmental stress situations.

PMID- 30284577
TI  - Emission of formic and acetic acids from two Colorado soils.
AB  - A 'missing source' of atmospheric formic acid is consistently observed during
      model-measurement comparisons, and evidence from multiple environments suggests a
      near-surface source. Soil emissions are considered to be a small formic acid
      source, but estimates are based on a single study from a tropical site. Here, we
      investigate soil emissions of organic acids from two soils - a ponderosa pine
      forest (Manitou Experimental Forest Observatory), and a managed lawn (Colorado
      State University) using a laboratory chamber. Both soils are a source of formic
      and acetic acids. Under ambient conditions, formic acid emissions are 0.11 (pine
      forest) and 0.15 (lawn) nmol m-2 s-1, and acetic acid emissions are 0.05 (pine
      forest) and 0.71 (lawn) nmol m-2 s-1. Only acetic acid emissions from the forest
      site correlate with CO2 fluxes, but all formic and acetic acid emissions increase
      exponentially with temperature. Increasing soil moisture only enhances acetic
      acid emissions from the forest. Considering this temperature and moisture
      dependence, we hypothesize that while equilibrium partitioning may contribute to
      the forest emissions, organic acid emissions from the lawn are likely driven by
      microbial activity. Lactic acid was emitted from both soils, but not quantified.
      The observed formic acid emissions are higher than previous measurements, but
      still low enough that soils are unlikely the 'missing source' of atmospheric
      organic acids, although the variability in the soil source is substantial. We
      contrast observations to previous parameterizations used in models, and present
      recommendations for modified parameterizations for formic and acetic acid
      emission.

PMID- 30284579
TI  - Knowledge and awareness of diabetes mellitus and its risk factors in Saudi
      Arabia.
AB  - OBJECTIVES: To summarize available peer-reviewed publications about public
      knowledge and awareness of diabetes mellitus (DM) among the population of Saudi
      Arabia. METHODS: We followed the standard reporting guidelines outlined in the
      PRISMA statement for the preparation of this systematic review. In February 2018
      we conducted literature searches of PubMed, Scopus, BIOSIS Citation Index, and
      Web of Science using the following keywords: "Knowledge" OR "Awareness" AND
      "Diabetes Mellitus" AND "Saudi Arabia." Records were screened, and relevant
      studies were selected and synthesized narratively. RESULTS: Nineteen articles are
      included in our systematic review. These studies included the following
      populations: DM patients (n=13), healthcare workers (n=3), medical students
      (n=1), secondary school students (n=1), and general population (n=1). Most
      studies found a lack of public awareness of the risk factors and complications of
      DM. Among medical students and healthcare workers, knowledge about the
      epidemiology of the disease and angle of insulin injection was deficient.
      CONCLUSION: This review highlights the need for increased knowledge and awareness
      of DM among the Saudi population. The means of improving knowledge and awareness
      of DM needs to be integrated into existing healthcare systems and processes to
      better inform patients, families and communities about this chronic disease.

PMID- 30284580
TI  - The long-term outcomes and histological transformation in class II lupus
      nephritis.
AB  - OBJECTIVES: To examined the short and long-term outcome of class II lupus
      nephritis (LN).   Methods: This retrospective study included patients with class
      II LN at their first renal biopsy between January 1996 and December 2016 in King
      Khaled University Hospital, Riyadh, Saudi Arabia. The rate of complete remission,
      worsening renal function, and histological transformation in the second biopsy
      were examined.   Results: The study included 32 female patients with class II LN.
      The most frequent presentation (62.5% of patients) was hematuria with
      subnephrotic range proteinuria. The clinical presentation included acute kidney
      injury in 22% of patients, and 9.4% had nephrotic range proteinuria. Management
      with steroid monotherapy in 25 patients resulted in complete remission for 92% of
      these patients at 6 months. After a median follow up of 8 years, 2 patients had a
      doubling of their serum creatinine. During the follow up 17 patients (53%) needed
      a second biopsy, which revealed  transformation to other classes (65%). 
      Conclusions: Daily steroid monotherapy may be an appropriate first-line treatment
      for class II LN that presents with subnephrotic range proteinuria and normal
      kidney function. Patients with acute kidney injury and/or nephrotic range
      proteinuria may warrant more aggressive immunosuppressive regimens.

PMID- 30284578
TI  - Review of surgical resection and reconstruction in head and neck cancer.
      Traditional versus current concepts.
AB  - This review summarizes the development of head and neck cancer resection and
      reconstruction. The developments in the treatment of cancer patients are
      reflected in their surgical outcomes, in addition to functional and aesthetic
      improvements. New technologies, such as surgical simulation and planning,
      minimally invasive surgery, and microsurgery have been added to the field to
      improve surgical resection of the tumor and reconstruction. The field is still
      growing to optimize the management of head and neck cancer.

PMID- 30284581
TI  - Histopathological pattern of skin cancer in Western region of Saudi Arabia. An 11
      years experience.
AB  - OBJECTIVES: To determine the histopathological pattern of skin cancer in Madinah
      region of Kingdom of Saudi Arabia (KSA). Methods: This is a retrospective study
      including all cases with a histological diagnosis of skin cancer diagnosed at the
      Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia, between
      January 2006 and December 2017. Data included  age, gender, site and histology of
      the tumor were collected from histopathological reports and analyzed using
      Statistical Package for the Social Sciences  (SPSS) Version 21. Results: Among
      the 202 cancer cases studied in our series, there were 124 (61.4%) cases of basal
      cell carcinoma (BCC), 33 (16.3%) cases of squamous cell carcinoma (SCC), 14
      (6.8%) cases of mycosis fungoides (MF), 12 (5.8%) cases of dermatofibrosarcoma
      protuberans (DFSP) and 7 (3.7%) cases of malignant melanomas (MM). The male to
      female ratio for all cases was 2.2:1. The ages ranged from 5 to 100 years with a
      mean age of 60.1+/-15 years. The peak age distribution was in the 60-69 year
      group. The most common site involved in BCC and SCC was the head and neck (92.7%
      and 66.7%) respectively). Acral distribution of MM was seen in 57.1% of the
      cases. Conclusion: Our data based on the histopathology history in the Madinah
      region match that in the world literature and Saudi national studies.

PMID- 30284582
TI  - Assessment of histopathological alterations in patients with chronic hepatitis B
      infection following long-term oral antiviral therapy.
AB  - OBJECTIVES: To evaluate the histopathological changes in the liver after oral
      antiviral therapy in patients with chronic hepatitis B. METHODS: A total of 79
      HBeAg-negative and positive patients who had been on lamivudine, entecavir, or
      tenofovir disoproxil for at least 3 years prior to inclusion were enrolled
      between March 2015 and 2016, retrospectively. There were 23 patients on
      lamivudine, 21 patients on entecavir, and 35 on tenofovir. All patients underwent
      a follow-up liver biopsy. Biochemical, serological, virological and
      histopathological data were recorded in all patients and were compared after at
      least 3 years of treatment with oral antiviral agents. Results: Histological
      activity index scores were reduced in patients who received lamivudine (p=0.011),
      entecavir (p=0.002), and tenofovir (p=0.001). Also, in contrast with a
      significant improvement in fibrosis scores in lamivudine (p=0.033) and tenofovir
      (p=0.001) groups no improvements were found in patients who received entecavir
      (p=0.090). Conclusion: Long term treatment with oral antiviral agents was
      associated with biochemical, virological, serological, and histopathological
      improvements. Long-term use of anti-viral agents as well as continuous
      suppression of HBV DNA are prerequisites for histopathological improvement.

PMID- 30284583
TI  - Evaluation of the perfusion index according to the visual analog scale in
      postoperative patients.
AB  - OBJECTIVES: To evaluate the possible value of the perfusion index (PI) as a tool
      for pain assessment. Methods: This prospective, observational study was performed
      with 89 patients underwent surgery with general anesthesia. The patients with
      visual analog scale (VAS) greater than 3 were grouped as M1, and patients with
      VAS<=3 and performed morphine were grouped as M2. After surgery patients with VAS
      greater than 3 were given 2mg morphine. Patients with VAS greater than 3 were
      given increments of intravenous morphine (2 mg) at 20 minute intervals until VAS
      less than 3. The correlation and difference between PI and VAS score values were
      evaluated before and after analgesic administration. Results: Significant changes
      were found in both PI values and VAS scores between M1 and M2 groups (2.80+/
      0.77, 3.97+/-0.94, p less than 0.001; 6.60+/-1.20, 2.74+/-0.46, p less than
      0.001) Despite no correlation was found between PI values and VAS scores of M1
      and M2 groups, weak negative correlation was detected between differences in PI
      values and VAS scores among groups (r=-0.255, p=0.016). Conclusion: Perfusion
      index is a parameter that can be used in the assessment of postoperative pain and
      responses to analgesics.

PMID- 30284584
TI  - Can we use serum Anti-Mullerian hormone to differentiate the diagnosis between
      polycystic ovary syndrome patients and healthy women with polycystic ovarian
      morphology and regular menstrual cycles.
AB  - OBJECTIVES: To compare Anti-Mullerian hormone (AMH) concentrations between
      polycystic ovary syndrome (PCOS)  patients and  healthy women who have polycystic
      ovarian morphology (PCOM) with regular menstrual cycles, and to determine a
      diagnostic cutoff value for PCOS women during reproductive period. Methods: This 
      study was carried out between February 2013 and October 2017 at the Department of
      Obstetrics and Gynecology, Izmir Katip Celebi University Ataturk Training and
      Research Hospital,  Izmir, Turkey. Seventy PCOS patients and 70 PCOM women with
      normal menstrual cycles were included in the study. Blood samples of the subjects
      were obtained following an 8-hour fast for AMH and biochemical assessments, serum
      gonadotropin, and androgen measurements. Results: The mean serum AMH levels of
      PCOS patients were found to be higher than PCOM women with normal menstrual
      cycles (p less than 0.01). The optimal serum AMH cutoff value for PCOS diagnosis
      was determined as 3.51 ng/ml (sensitivity 72.8%, specificity 75.7%). Conclusion:
      Serum AMH concentrations are significantly higher in PCOS patients independent
      from the ovarian morphology and number of follicles per ovary. Positive and
      negative predictive values of AMH in PCOS diagnosis were found to be 75% and
      73.6%, respectively, with a cutoff value of 3.51 ng/mL.

PMID- 30284585
TI  - Evaluation of the effects of dexmedetomidine and remifentanil on pain with the
      analgesia nociception index in the perioperative period in hysteroscopies under
      general anesthesia. A randomized prospective study.
AB  - Objectives To compare analgesia nociception index (ANI) values, visual analog
      scale (VAS) values, and hemodynamic parameters in hysteroscopy patients who
      received remifentanil and dexmedetomidine during general anesthesia. Methods: In
      total, 30 patients who underwent hysteroscopy between March and September 2016 at
      the University of Health Sciences Fatih Sultan Mehmet Health Research and
      Application Center, Ankara, Turkey were included in this prospective study.
      Standard hemodynamic monitoring, ANI, and bispectral index (BIS) monitoring were
      applied to the patients. At 10 min prior to induction, 1 MUg/kg of remifentanil
      was applied in Group R (n=15) and 1 MUg/kg of dexmedetomidine was applied in
      Group D (n=15). After induction, sevoflurane was used for maintenance with
      dexmedetomidine at 0.2-0.7 MUg/kg/hour in Group D and remifentanil at 0.05-0.5
      MUg/kg/minute in Group R. Perioperative and postoperative analgesia levels (ANI
      and VAS, respectively), hemodynamics, and complications were recorded. Results:
      Even though the ANI levels in Group D were lower at the perioperative 5th and
      10th minutes, the ANI values were between the targeted limits, except for the
      measurement after I-gel insertion, in both groups. Hemodynamic parameters were
      within normal limits, but the mean arterial pressures in Group R after induction,
      following I-gel placement, and at the perioperative 5th, 10th, and 20th minutes
      were lower and at  postoperative 30th minute were significantly higher.  
      Conclusion: Dexmedetomidine and remifentanil are both efficacious agents for
      perioperative analgesia in hysteroscopy cases.

PMID- 30284586
TI  - Effect of preoperative hydromorphone in patients undergoing laparoscopic radical
      gastrectomy. A double-blind, randomized and controlled trial.
AB  - OBJECTIVES: To determine the efficacy of preemptive hydromorphone for
      laparoscopic radical gastrectomy. Methods: The present prospective and double
      blinded study was performed in the The First Hospital, Jilin University,
      Changchun, China, between July 2017 and April 2018. Fifty patients scheduled for
      laparoscopic radical gastrectomy were equally randomized into 2 groups, which
      were administrated different drugs 10 minutes before surgery. Group P (the
      preemptive hydromorphone group) was administrated 2 mg hydromorphone (2 mL), and
      Group C (the control group) was administrated 2 mL normal saline intravenously. A
      standardized general anesthesia were conducted. Blood pressure and heart rate,
      postoperative morphine consumption, pain intensity, sedation status, and side
      effects were recorded. Results: Group C had larger intraoperative hemodynamic
      changes, higher postoperative visual analogue scale score, more morphine
      consumption and lower overall satisfaction degree than Group P. No difference was
      found between the 2 groups in sedation status and adverse effects.  Conclusion:
      Preoperative 2 mg hydromorphone could reduce intraoperative changes of blood
      pressure and heart rate, postoperative pain intensity, and morphine consumption
      without an increase of adverse effects.

PMID- 30284587
TI  - Evaluation of the effects of different treatment modalities on angiogenesis in
      heart failure patients with reduced/mid-range ejection fraction via VEGF and
      sVEGFR-1.
AB  - OBJECTIVES: To investigate the clinical significance of VEGF, sVEGFR-1 in heart
      failure reduced ejection fraction (HFrEF) and heart failure mid-range ejection
      fraction (HFmrEF) patients. Methods: A total of 104 people consisting of HFrEF
      and HFmrEF patients (n=54) and healthy (n=50) subjects were included in this
      comparative cross-sectional study. The study took place in Gulhane Training and
      Research Hospital, Ankara, Turkey, between  2011 and 2013. Serum VEGF, sVEGFR-1,
      plasma pro-BNP analysis and transthoracic echocardiography were performed. 
      Results: The average sVEGFR-1 level of the HFrEF and HFmrEF patients was
      significantly higher than the control group (0.185+/-0.122; 0.141+/-0.120;
      p=0.013). The average sVEGFR-1 level of the HFrEF and HFmrEF patients using beta
      blocker was significantly higher than the HFrEF and HFmrEF patients not using it
      (p=0.015). There was a significant and positive correlation between sVEGFR-1 and
      N-terminal pro-brain natriuretic peptide (pro-BNP)  levels in the group with HF
      (r=0.211, p=0.044). Conclusion: It increases awareness about the role of sVEGFR-1
      in HFrEF anf HFmrEF patients and the need for further studies. Beta-blocker may
      have a negative effect on angiogenesis in HFrEF and HFmrEF via increasing sVEGFR
      1 levels. Additionally, Pro-BNP may contribute to inhibiting angiogenesis by
      increasing sVEGFR-1 levels and sVEGFR-1 may be an important biomarker in HFrEF
      and HFmrEF.

PMID- 30284588
TI  - High antimicrobial resistant rates among Gram-negative pathogens in intensive
      care units. A retrospective study at a tertiary care hospital in Southwest Saudi
      Arabia.
AB  - OBJECTIVES: To determine the distribution and resistance profiles of Gram
      negative bacteria (GNB) in intensive care units (ICUs) at King Abdullah Hospital
      in Bisha, Saudi Arabia. Methods: A record based retrospective study was conducted
      from December 2016 to January 2018. In total, 3736 non-duplicate clinical
      specimens from the general intensive care unit (ICU), neonatal ICU (NICU), and
      coronary CU (CCU) were analyzed for pathogens. Results: Of 3736 specimens, 9.6%
      (358) were positive for pathogens, and GNB constituted the majority (290/358;
      81%). Acinetobacter is predominant in the general ICU, whereas Klebsiella
      pneumoniae is common in the NICU and CCU. Overall, GNB revealed a high resistance
      rate for cefuroxime (75.8%) trimethoprim/sulfamethoxazole (73.4%), cefotaxime
      (72.9%), aztreonam (64.6%), piperacillin (62.1%), and ciprofloxacin (61.5%).
      Acinetobacter revealed a high resistance (93.4% to 97.5%) to all antimicrobials
      except colistin (4%). Klebsiella pneumoniae showed a high resistance to
      trimethoprim/sulfamethoxazole (71.8%), cefotaxime (71.4%) and aztreonam (65.2%).
      Pseudomonas aeruginosa showed good activity for aminoglycosides but increasing
      resistance for cephalosporins and meropenem. GNB exhibited a high rate of multi
      drug-resistant (MDR) phenotypes (67.9%) with a higher level among Acinetobacter
      spp. (97.5%). There were no significant differences in the resistance rates of
      GNB from different ICUs except for imipenem (p=0.002) and ciprofloxacin
      (p=0.003).  Conclusions: Increased antimicrobial resistance with high proportions
      of MDR patterns were found among GNB from ICUs. Comprehensive surveillance
      programs are needed to track the origins and emergence pathways of resistant
      pathogens.

PMID- 30284589
TI  - The importance of hand hygiene education on primary schoolgirls' absence due to
      upper respiratory infections in Saudi Arabia. A cluster randomized controlled
      trial.
AB  - OBJECTIVES: To quantify the reduction in absence due to upper respiratory
      infections (URIs) among primary schoolgirls attending Riyadh's schools after
      delivering a hand hygiene workshop intervention over a period of 5 weeks.
      Methods: A cluster randomized trial was conducted among girls attending 4 primary
      schools between January and March 2018. The participants attended a hand hygiene
      workshop. The schoolgirls' absences were followed up for 5 weeks. Incidence rate,
      percentage of absence days, and absence rate were calculated for total and URIs
      absences. Result: Total number of participating schoolgirls was 496. Upper
      respiratory infections accounted for 15.3% of absence episodes. Schoolgirls lost
      521 days of school and 19.4% of them were URIs-related. Absence rate due to URIs
      were 12.4 and 23.4 as well as 5.62 and 11.72 per 100 schoolgirls in the control
      (CG) and experimental (EG) groups, respectively. Percentage of absence days were
      lower in the experimental group (CG: 0.86% and 1.39% versus EG: 0.39% and 0.72%).
      Incidence rates of absence due to URIs were 0.54 and 1.02 in CG versus 0.24 and
      0.51 in EG per 100 schoolgirls per day. Conclusion: There could be further
      reduction in school absences if education was accompanied by hand soap
      dissemination. The study could serve as a pilot for major studies in the future.
      Sustainability of the intervention can be tested in studies with longer
      durations.

PMID- 30284590
TI  - Staphylococcus lugdunensis from gluteal abscess to destructive native triple
      valve endocarditis.
AB  - We herein present the case of a 43-year-old male diabetic patient who presented
      with an aggressive form of infective endocarditis involving the tricuspid, mitral
      and aortic valves following a gluteal abscess due to infection with
      Staphylococcus lugdunensis. This coagulase-negative organism which is generally
      considered a component of the normal flora of the skin has however recently
      emerged as an unusually virulent pathogen responsible for both nosocomial and
      community-acquired infections. The case demonstrates the importance of paying
      utmost attention and ensuring a logical conclusion to the identification of
      persistent coagulase-negative blood cultures. In addition, it also shows the
      importance of early identification of this organism and aggressive antibiotic
      administration to avert endocarditis because of the unusual virulence of the
      organism. Staphylococcus lugdunensis is rarely a clinical specimen contaminant,
      and its isolation warrants further investigation and concerted treatment.

PMID- 30284591
TI  - Is the art of assisted breech delivery still fading in the Kingdom of Saudi
      Arabia?
AB  - [No Abstract Available].

PMID- 30284592
TI  - Incidental right-sided diaphragmatic eventration after blunt thoracoabdominal
      trauma.
AB  - [No Abstract Available].

PMID- 30284593
TI  - Pediatric systemic lupus erythematosus. Retrospective analysis of clinico
      laboratory parameters and their association with systemic lupus erythematosus
      disease activity index score.
AB  - [No Abstract Available].

PMID- 30284594
TI  - James Crichton-Browne (1840-1938).

PMID- 30284595
TI  - Oral administration of oat beta-glucan preparations of different molecular weight
      results in regulation of genes connected with immune response in peripheral blood
      of rats with LPS-induced enteritis.
AB  - PURPOSE: Beta-glucans are biologically active polysaccharides having antioxidant,
      immunomodulatory, and antiinflammatory properties. This study investigated the
      transcriptomic profile in peripheral blood of rats with LPS-induced enteritis,
      which were fed a diet supplemented with high- (G1) and low- (G2) molecular-weight
      oat beta-glucans. METHODS: Two-color rat gene expression microarrays were applied
      and the analysis was performed using a common reference design to provide easy
      means of comparing samples from various experimental conditions against one
      another. Common reference sample was labeled with cyanine 3 (Cy3) and
      investigated samples from each experimental group: C-G0 (control group fed semi
      synthetic diet), LPS-G0 (LPS-challenged group fed semi-synthetic diet), LPS-G1
      (LPS-challenged group fed G1 beta-glucan enriched diet), and LPS-G2 (LPS
      challenged group fed G2 beta-glucan enriched diet) were labeled with cyanine 5
      (Cy5). Each microarray was performed in quadruplicate. Statistical analysis was
      performed using one-way ANOVA and Tukey's HSD post-hoc test (p < 0.05). A
      multiple testing correction was performed using Benjamini and Hochberg False
      Discovery Rate < 5%. A quantitative real-time RT-PCR was performed to verify the
      expression of chosen transcripts. RESULTS: The microarray analyses revealed
      differentially expressed transcripts between: the LPS-G0 and the control groups:
      C-G0 (138 genes), the LPS-G1 and LPS-G0 groups (533 genes), and the LPS-G2 and
      LPS-G0 groups (97 genes). Several differentially expressed genes in the beta
      glucan-supplemented groups encoded proteins belonging to TLR and NLR signaling
      pathways, as well as prostaglandin synthesis and regulation pathways. Both beta
      glucans up-regulated the expression of Atg10, which belongs to the family of
      autophagy-related genes, suggesting a possible link between autophagy induction
      and beta-glucan supplementation. CONCLUSION: The changes in gene expression
      observed in the peripheral blood indicate that oat beta-glucans exerted a
      protective effect in rats with an induced inflammatory state caused by LPS
      challenge. The greater number of differentially expressed genes was observed in
      group supplemented with G1 beta-glucan, pointing at the differences in the mode
      of action of high- and low-molecular-weight beta-glucans in the organism.

PMID- 30284596
TI  - Effects of MDPV on dopamine transporter regulation in male rats. Comparison with
      cocaine.
AB  - RATIONALE: MDPV (3,4-methylenedioxypyrovalerone) is a synthetic cathinone present
      in bath salts. It is a powerful psychostimulant and blocker of the dopamine
      transporter (DAT), like cocaine. It is known that acute exposure to
      psychostimulants induces rapid changes in DAT function. OBJECTIVES: To
      investigate the effects of MDPV on DAT function comparing with cocaine. METHODS:
      Binding of [3H]WIN 35428 was performed on PC 12 cells treated with MDPV and
      washed. Rat striatal synaptosomes were incubated with MDPV or cocaine (1 MUM) for
      1 h and [3H]dopamine (DA) uptake was performed. Also, different treatments with
      MDPV or cocaine were performed in Sprague-Dawley rats to assess locomotor
      activity and ex vivo [3H]DA uptake. RESULTS: MDPV increased surface [3H]WIN 35428
      binding on PC 12 cells. In vitro incubation of synaptosomes with MDPV produced
      significant increases in Vmax and KM for [3H]DA uptake. In synaptosomes from MDPV
      (1.5 mg/kg, s.c.) and cocaine- (30 mg/kg, i.p.) treated rats, there was a
      significantly higher and more persistent increase in [3H]DA uptake in the case of
      MDPV than cocaine. Repeated doses of MDPV developed tolerance to this DAT
      upregulation and 24 h after the 5-day treatment with MDPV, [3H]DA uptake was
      reduced. However, a challenge with the same drugs after withdrawal recovered the
      DAT upregulation by both drugs and showed an increased response to MDPV vs the
      first dose. At the same time, animals were sensitized to the stereotypies induced
      by both psychostimulants. CONCLUSIONS: MDPV induces a rapid and reversible
      functional upregulation of DAT more powerfully and lasting than cocaine.

PMID- 30284597
TI  - Interaction potential of the dual orexin receptor antagonist ACT-541468 with
      CYP3A4 and food: results from two interaction studies.
AB  - PURPOSE: ACT-541468 is a novel dual orexin receptor antagonist (DORA) under
      development for the treatment of insomnia. In vitro studies suggested a
      significant role of CYP3A4 in ACT-541468 metabolism and an impact on CYP3A4
      activity. METHODS: Subsequently, two clinical cross-over studies investigated the
      victim (n = 14 healthy subjects) and perpetrator (n = 20) potential of 25 mg ACT
      541468 with respect to CYP3A4. The effect of food intake on the pharmacokinetics
      of ACT-541468 was also investigated. RESULTS: Moderate CYP3A4 inhibition by
      diltiazem (240 mg/day) increased the Cmax and AUC0-infinity of ACT-541468 by 1.4
      fold (90% confidence interval (CI): 1.2-1.6) and 2.4-fold (90% CI: 2.0-2.8),
      respectively, and prolonged t1/2 by 80% (90% CI: 60-90) without affecting tmax.
      Single- and multiple-dose administration of 25 mg ACT-541468 had no impact on the
      pharmacokinetics of the sensitive substrate midazolam and its main metabolite 1
      hydroxy midazolam indicated by 90% CI of the geometric mean ratios of Cmax and
      AUC within bioequivalence criteria and by an unchanged tmax. After a high-fat
      high-calorie breakfast, the pharmacokinetic profile of 25 mg ACT-541468 showed a
      decrease of Cmax by 24% (90% CI: 17-31) and a delay of tmax by approximately 2 h
      (90% CI: 1.4-2.4), whereas t1/2 and AUC0-24 remained essentially unchanged. ACT
      541468 given alone or in combination with diltiazem, midazolam, or food was safe
      and well tolerated. CONCLUSIONS: Overall, ACT-541468 has been determined as
      CYP3A4 substrate but without any perpetrator drug-drug interaction potential
      regarding CYP3A4 in humans. Food affected ACT-541468 absorption without modifying
      overall exposure.

PMID- 30284598
TI  - [What is verified for travel vaccinations?]
AB  - Vaccinations are among the most effective preventive measures modern medicine has
      to offer. They lead both to individual protection in those vaccinated and in many
      cases to the protection of others against transmission of the infection; however,
      the acceptance of vaccinations in Germany has declined rather than increased in
      recent years. Paradoxically, this is very much due to the success of the
      vaccinations: due to successful immunization campaigns, numerous diseases have
      become so rare that they have disappeared from the consciousness of the
      population. Travel medicine counselling offers an excellent opportunity to fill
      in gaps in immunization.

PMID- 30284599
TI  - Psychometric validation of the self-identification of having a mental illness
      (SELF-I) scale and the relationship with stigma and help-seeking among young
      people.
AB  - PURPOSE: Self-identification of having a mental illness has been shown to be an
      important factor underpinning help-seeking behaviour and may mediate the
      relationship between personal stigma and mental health service use. This study
      validates a new scale for the self-identification of having a mental illness
      among a non-clinical, community cohort of young people in the UK. METHODS:
      Following consultation with a group of young person experts with experience of
      mental health problems, we evaluated the psychometric properties of the self
      identification of mental illness scale (SELF-I) among 423 young people aged 13-24
      years who are part of an ongoing prospective community cohort. We performed test
      retest reliability among a subset of 53 participants. Psychometric validation for
      the scale used measures of Cronbach's alpha and Pearson's correlation
      coefficient. Item performance was assessed along and in relation with each
      covariate. RESULTS: The SELF-I demonstrated robust psychometric properties
      including high test-retest reliability (0.95) and good internal consistency (0.87
      as determined by the Cronbach's alpha). The inter-total correlations for each
      item, which ranged from 0.62 to 0.74, supported keeping all items in the scale.
      Reporting greater psychiatric symptomatology via the SDQ (beta: 0.82 95%
      confidence interval 0.40, 1.23), psychotic-like experiences (beta: 0.37 95%
      confidence interval 0.14, 0.59), and use of mental health services (beta: 0.92
      95% confidence interval 0.71, 1.13) were associated with a greater self
      perception as having a mental illness (p < 0.05), providing evidence of
      convergent validity. As expected, we found that less intended stigmatising
      behaviour was associated with greater self-perceptions of having a mental illness
      (B: 0.18, 95% CI 0.07, 0.28). CONCLUSIONS: The SELF-I scale provides a method to
      gather insight into how young people, who may not identify as service users,
      perceive their own mental state and potential risk for developing a mental
      illness. This can be important for understanding perceived need for help and
      likelihood of using services among those with mental health problems.

PMID- 30284601
TI  - Abstracts from 38th Congress of the Societe Internationale d'Urologie Seoul
      Dragon City, October 4-7, 2018.

PMID- 30284600
TI  - Hepatic zonation of toxic metabolite formation: perspectives of matrix-assisted
      laser desorption mass spectrometry imaging.

PMID- 30284602
TI  - Mangrove Sediment Microbiome: Adaptive Microbial Assemblages and Their Routed
      Biogeochemical Processes in Yunxiao Mangrove National Nature Reserve, China.
AB  - Microorganisms play important roles in mangrove ecosystems. However, we know
      little about the ecological implications of mangrove microbiomes for high
      productivity and the efficient circulation of elements in mangrove ecosystems.
      Here, we focused on mangrove sediments located at the Yunxiao National Mangrove
      Reserve in southeast China, uncovering the mangrove microbiome using the 16S rRNA
      gene and shotgun metagenome sequencing approaches. Physicochemical assays
      characterized the Yunxiao mangrove sediments as carbon (C)-rich, sulfur (S)-rich,
      and nitrogen (N)-limited environment. Then phylogenetic analysis profiling a
      distinctive microbiome with an unexpected high frequency of Chloroflexi and
      Nitrospirae appeared to be an adaptive characteristic of microbial structure in S
      rich habitat. Metagenome sequencing analysis revealed that the metabolic pathways
      of N and S cycling at the community-level were routed through ammonification and
      dissimilatory nitrate reduction to ammonium for N conservation in this N-limited
      habitat, and dissimilatory sulfate reduction along with polysulfide formation for
      generating bioavailable S resource avoiding the biotoxicity of sulfide in
      mangrove sediments. In addition, methane metabolism acted as a bridge to connect
      C cycling to N and S cycling. Further identification of possible biogeochemical
      linkers suggested Syntrophobacter, Sulfurovum, Nitrospira, and Anaerolinea
      potentially drive the coupling of C, N, and S cycling. These results highlighting
      the adaptive routed metabolism flow, a previously undescribed property of
      mangrove sediment microbiome, appears to be a defining characteristic of this
      habitat and may significantly contribute to the high productivity of mangrove
      ecosystems, which could be used as indicators for the health and biodiversity of
      mangrove ecosystems.

PMID- 30284603
TI  - A phase II study of NK012, a polymeric micelle formulation of SN-38, in
      unresectable, metastatic or recurrent colorectal cancer patients.
AB  - PURPOSE: NK012 is a polymeric micelle formulation of SN-38, the active metabolite
      of irinotecan. We evaluated the efficacy and safety of NK012 in Japanese patients
      with unresectable metastatic colorectal cancer. METHODS: We conducted a
      multicenter open-label phase II trial of NK012 monotherapy in 58 patients who had
      been treated with an oxaliplatin-based chemotherapy regimen (group A: 53 patients
      with UGT1A1 genotype -/-, *6/-, or *28/-; group B: 5 patients with UGT1A1
      genotype *6/*28 or *6/*6). The primary endpoint was the response rate (RR).
      Initial doses of 28 and 18 mg/m2 for group A and group B, respectively, were
      administered intravenously over 30 min, and these doses were subsequently
      administered every 3 weeks. Group A was evaluated as the primary efficacy
      population, while group B was evaluated for reference. RESULTS: In group A, the
      RR was 3.8%, and the median progression-free survival and overall survival were
      3.30 months and 15.03 months, respectively. In both groups, the most common grade
      >= 3 adverse drug reaction (ADR) was neutropenia and the incidence of grade >= 3
      diarrhea was low or zero. In group A, 17 serious ADRs were observed in 10
      patients (17%); all improved or recovered. In group B, no serious ADRs were
      observed. No treatment-related deaths were reported in either group. CONCLUSIONS:
      NK012 monotherapy yielded an RR similar to the RR of irinotecan monotherapy that
      was reported in the phase III EPIC trial (4.2%), and the incidence of grade >= 3
      diarrhea was low. Based on the incidence and severity of febrile neutropenia and
      grade >= 3 neutropenia, the initial dose of NK012 28 mg/m2 may be too high for
      colorectal cancer patients who have previously been treated with an oxaliplatin
      based chemotherapy regimen.

PMID- 30284604
TI  - Correction to: ''Bunch of grapes'' in complete hydatidiform mole.
AB  - The original version of this article contained a mistake in the co-author's first
      name. The co-author name should read as "Mariana Athaniel Silva Rodrigues"
      instead of "Marina Athaniel Silva Rodrigues". It is now corrected with this
      erratum.

PMID- 30284605
TI  - Combined host-guest complex with coffee-ring effect for constructing
      ultrasensitive SERS substrate for phenformin hydrochloride detection in
      healthcare products.
AB  - Phenformin hydrochloride (PHE), once used as a traditional anti-diabetic drug,
      has now been banned due to significant side effects. However, the phenomenon of
      the illegal addition of PHE to hypoglycemic healthcare products is still rampant.
      Thus, the detection of illegally added PHE is urgently needed. Surface-enhanced
      Raman scattering (SERS) is a promising candidate for this purpose, but the weak
      affinity between PHE and bare metal (Au or Ag) limits direct SERS detection of
      PHE. In this paper, we prepared Ag nanoparticles coated with beta-cyclodextrin
      (AgNP@beta-CD), which display the coffee-ring effect, that can be used for PHE
      sensing. beta-CD-functionalized nanoparticles could capture the analyte and fix
      the molecular orientation in the hydrophobic cavity. The coffee-ring effect could
      improve the SERS effect through a higher concentration of the analyte, higher
      density of nanoparticles, and more hot spots. The SERS performance of the
      AgNP@beta-CD substrate was characterized by using o-phenylenediamine
      dihydrochloride as a probe molecule. The excitation wavelength and pH value were
      optimized. A linear response for PHE detection is in the 7.0 * 10-8-1.0 * 10-6
      mol L-1 concentration range, and the limit of detection is as low as 8.0 * 10-9
      mol L-1. This AgNP@beta-CD coffee-ring effect substrate was applied to the
      detection of PHE in healthcare products, with recoveries between 95.3 and 105.0%
      and relative standard deviations of less than 5.16%. It is anticipated that the
      AgNP@beta-CD substrate will also have great potential for the monitoring of other
      aromatic drugs in healthcare products.

PMID- 30284606
TI  - Fractures in patients with osteopetrosis, insights from a single institution.
AB  - PURPOSE: Osteopetrosis is a hereditary skeletal disorder in which defective
      osteoclast function leads to abnormally hard and brittle bones. This study aims
      to describe the pattern of fractures occurring in this group of patients,
      possible complications, and strategies to avoid them. METHODS: This is a case
      series of six osteopetrotic patients with a total of 12 fractures managed in our
      institution over a period of nine years. Patient records were also reviewed for
      complications both intra- and post-operatively. RESULTS: The majority of the
      fractures involved the femur, with three of these being peri-implant in nature.
      Other bones involved include the tibia, humerus, patella, fifth metatarsal, and
      proximal phalanx of the toe. There was a high rate of complications while
      managing these patients: three patients had peri-implant stress fractures, three
      with retained broken screws, and one case each of delayed union, non-union, and
      surgical site infection. CONCLUSION: Osteopetrosis fractures present a unique
      challenge to the orthopedic surgeon. Careful pre-operative planning should be
      undertaken before proceeding with surgery in these cases.

PMID- 30284607
TI  - The anterior-based muscle-sparing approach to the hip: the "other" anterior
      approach to the hip.
AB  - PURPOSE: The purpose of this study was to evaluate safety, efficacy, and learning
      curves of anterior-based muscle-sparing total hip arthroplasty (ABMS-THA) in the
      supine position. Furthermore, early functional outcome was evaluated and compared
      to direct anterior approach (DAA) by measuring surface electromyography (sEMG).
      METHODS: We present a prospective cohort study of 343 hips. The safety and
      learning curve were assessed by recording operative time and peri-operative
      adverse events. For assessment of efficacy, functional and radiological outcomes
      were evaluated. A selected group of 32 patients have been studied by sEMG and
      compared to a matched group of 32 patients who received a THA using DAA approach.
      RESULTS: There was one dislocation (0.3%); two (0.6%) patients had an intra
      operative fractures of the greater trochanter; two patients (0.6%) experienced a
      self-limited femoral nerve palsy. Physical therapy milestones for hospital
      discharge were reached on an average of 1.7 days. sEMG showed that ABMS and DAA
      have a similar muscle recruitment pattern and functional recovery after THA. One
      patient was revised for infection, 16 were lost, and 326 hips were available with
      a median follow-up of 42 months (range 24-60). The mean Harris Hip Score (HSS)
      increased from 44.3 to 91.9. Ninety-six percent of the hips had a leg length
      discrepancy (LLD) < 5 mm. There were no radiological signs of mechanical
      loosening or osteolysis. CONCLUSIONS: The ABMS approach in the supine position is
      clinically effective and safe; special advantages include a very low dislocation
      rate and a great control of LLD.

PMID- 30284608
TI  - Dynamics of WNT signaling components in the human ovary from development to
      adulthood.
AB  - WNT signaling has been shown to play a pivotal role in mammalian gonad
      development and sex differentiation; however, its role in the developing human
      ovary has not been investigated. We analyzed a quantitative mass spectrometry
      dataset to determine the expression of WNT signaling components between 47 and
      137 days of development and in adult ovarian cortex tissue. WNT signaling was
      identified within the top ten canonical pathways of proteins detected at every
      developmental stage examined. We further examined the specific localization of
      WNT signaling components glycogen synthase kinase 3 (GSK3B), frizzled 2 (FZD2),
      and beta-catenin (CTNNB1) within ovarian tissue. GSK3B was nearly ubiquitously
      expressed during fetal development, while FZD2 was specific to germ cell nests
      during early development. beta-catenin exhibited translocation from primarily
      membrane bound during early ovarian development to cytoplasmic and nuclear
      staining specifically in early primordial follicles in the fetal ovary. This
      cytoplasmic and nuclear beta-catenin persisted in primordial follicles in adult
      ovarian tissue, but returned to membrane-bound localization in secondary
      follicles. We conclude that WNT signaling components are expressed in the human
      ovary from early to mid-gestation and remain in the adult ovary, and observed
      evidence for canonical WNT signaling only in the oocytes of primordial follicles.
      Together, these data are indicative of a role for canonical WNT signaling via
      beta-catenin nuclear translocation during human follicle formation and follicle
      maintenance.

PMID- 30284609
TI  - Anisomycin, a JNK and p38 activator, suppresses cell-cell junction formation in
      2D cultures of K38 mouse keratinocyte cells and reduces claudin-7 expression,
      with an increase of paracellular permeability in 3D cultures.
AB  - Keratinocytes in the oral mucosal epithelium, which is a non-keratinized
      stratified epithelium, are exposed to various stimuli from the oral cavity. JNK
      and p38 are stress-activated mitogen-activated protein kinases (MAPKs) that are
      phosphorylated by various stimuli and are involved in the assembly and
      disassembly of tight junctions (TJs) in keratinocytes. Therefore, we investigated
      the effects of stress-activated MAPKs on TJs in a mouse keratinocyte cell line
      during cell-cell junction formation in two-dimensional (2D) cultures or
      stratification to form non-keratinized epithelium in 3D cultures. In 2D cultures,
      calcium induced zipper-like staining for ZO-1 at 2 h and string-like staining for
      ZO-1 at 12 h, which indicated immature and mature cell-cell junctions,
      respectively. Anisomycin (AM), a JNK and p38 activator, inhibited formation of
      string-like staining for ZO-1, whereas inhibition of JNK, but not p38, after AM
      treatment restored string-like staining for ZO-1, although claudins (CLDNs) 4, 6,
      and 7 did not completely colocalize to ZO-1-positive sites. In 3D cultures, AM
      treatment for 2 weeks activated only p38, suppressed flattening of the
      superficial cells, removed CLDN7 from ZO-1-positive spots on the surface of 3D
      cultures, which represent TJs, and decreased transepithelial electrical
      resistance. Thus, short-term AM treatment inhibited maturation of cell-cell
      junctions by JNK, but not p38, activation. p38 activation by long-term AM
      treatment affected morphology of stratified structures and paracellular
      permeability, which was increased by CLDN7 removal from TJs. Various chronic
      stimuli that activate stress-activated MAPKs may weaken the keratinocyte barrier
      and be involved in TJ-related diseases.

PMID- 30284610
TI  - Morphological characteristics of optical coherence tomography defined plaque
      fissure in patients with acute coronary syndrome.
AB  - We assessed the plaque disruption in 245 consecutive patients with acute coronary
      syndrome undergoing percutaneous coronary intervention. The plaque fissure was
      diagnosed with optical coherence tomography, and intravascular ultrasound was
      used to determine arterial remodeling. Of them, 26 fissures were found in this
      study. The definite fissure was seen in 17 (65.4%) and probable fissure was seen
      in 9 (34.6%) patients. In 18 (69.2%), plaque fissure component was lipidic or
      thin-capped fibroatheroma. Eighteen (69.2%) of fissured plaque were seen within
      30 mm of coronary ostium. Combined plaque fissure with plaque rupture/erosion was
      seen in 21 (80.8%) cases. The isolated fissure was seen in 5 (19.2%). Compared to
      the maximal necrotic core site of the ruptured plaque, the fissure site showed a
      smaller %necrotic core (p = 0.012), however, greater in fissure site than minimal
      lumen area site (24.93 +/- 11.50% vs 15.34 +/- 10.40%, p < 0.0001). The
      remodeling index was higher at fissure site as compared to minimal lumen area
      site (1.02 +/- 0.22 vs 0.94 +/- 0.27; p = 0.047), but similar to the rupture
      plaque (p = 0.31). The frequency of positive remodeling was 34.6% (9/26) at the
      plaque fissure. Although the plaque fissure can be interchangeable with the
      rupture in acute coronary syndrome, the limited extension to the small lipid core
      might and less positive remodeling provoke a fissuring of the plaque. Further
      study is necessary to assess the plaque fissure.

PMID- 30284612
TI  - Advancing EJNMMI: continuing success and next developments.

PMID- 30284611
TI  - Progression of ductal carcinoma in situ to invasive breast cancer: comparative
      genomic sequencing.
AB  - Several models have been described as potential mechanisms for the progression of
      ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC). The aim of our
      study was to increase our understanding of DCIS progression by using massive
      parallel sequencing of synchronous DCIS and IBC. We included patients with
      synchronous DCIS and IBC (n = 4). Initially, IBC and normal tissue were subjected
      to whole exome sequencing. Subsequently, targeted sequencing was performed to
      validate those tumor-specific variants identified by whole exome sequencing.
      Finally, we analyzed whether those specific variants of the invasive component
      were also present in the DCIS component. There was a high genomic concordance
      between synchronous DCIS and IBC (52 out of 92 mutations were present in both
      components). However, the remaining mutations (40 out of 92) were restricted to
      the invasive component. The proportion of tumor cells with these mutations was
      higher in the invasive component compared to the DCIS component in a subset of
      patients. Our findings support the theory that the progression from DCIS to IBC
      could be driven by the selection of subclones with specific genetic aberrations.
      This knowledge improves our understanding of DCIS progression, which may lead to
      the identification of potential markers of progression and novel therapeutic
      targets in order to develop a more personalized treatment of patients with DCIS.

PMID- 30284613
TI  - Pre-peritoneal pelvic packing for the management of life-threatening pelvic
      fractures.
AB  - BACKGROUND: Pre-peritoneal pelvic packing (PPP) is a technique used for treating
      pelvic hemorrhage in patients with pelvic fractures and hemodynamic instability
      after a high-energy trauma representing a life-threatening situation. The aim of
      this study was to perform a comprehensive review of the literature. METHODS: A
      review of the medical literature was performed, based on the following inclusion
      criteria: patients sustaining pelvic fractures with hemodynamic instability and
      the inclusion of PPP as a tool for hemorrhage control. Articles not involving
      human patients, review articles, surveys, pediatric patients, hemodynamic
      stability, case reports, and not directly related publications; such as
      angiography with or without embolization, and REBOA use for hemorrhage control as
      a primary outcome evaluation were excluded from this search. RESULTS: Eleven
      articles out of seventy-seven identified publications between 2008 and 2018 met
      the inclusion criteria and were included in this review. CONCLUSIONS: PPP is a
      surgical approach used in life-threatening situations due to pelvic fracture with
      high risk of death for exsanguination. Performed expediently, good results can be
      obtained with a decrease in the need for blood products, improved systolic blood
      pressure, and a decrease in mortality rates overall. This makes PPP an important
      life-saving tool.

PMID- 30284614
TI  - [Anemia in the aged - a geriatric syndrome? : Second position paper on anemia in
      the aged by the working group anemia of the German Geriatric Society].
AB  - Geriatric syndromes are the pathognomonic columns of geriatric medicine. In
      contrast to many syndromes in younger people, in geriatric patients, the chief
      complaint does not typically represent the specific pathological condition
      underlying the change in health status. Geriatric syndromes are usually highly
      prevalent, multicausal and share a number of common risk factors. In recent
      years, scientific controversy over anemia in the aged has revealed a high
      prevalence in geriatric patients, which prompted the "working group on anemia" to
      publish its first position paper at a European level. The development of anemia
      is multicausal and the causes of the various forms of anemia range from iron
      deficiency, malnutrition, chronic inflammation, hormonal dysregulation,
      functional organ disorders, impaired synthesis to malignancies. The corresponding
      pathomechanisms are closely associated with the development of other geriatric
      syndromes such as gait disorders, sarcopenia, frailty, and falls. Against this
      backdrop, the "working group on anemia" of the German Geriatric Society has
      devised a second position paper:"Multicausality and the significant association
      between anemia and assessment-based quantifiable impairments suggest the
      consideration of anemia in the aged to be a geriatric syndrome."

PMID- 30284615
TI  - Establishment of Fascioloides magna in a new region of Hungary: case report.
AB  - During the monitoring of red deer (N = 124) and fallow deer (N = 13) populations
      in four neighbouring areas, the presence of Fascioloides magna was confirmed in
      southwestern Hungary. The prevalence and the mean intensity of the infection
      within the host populations ranged between 0 and 100% and 0-36.3, respectively.
      The determined prevalences are similar to that observed earlier in other European
      natural foci. The authors hypothesise that the appearance of F. magna in this
      region should have been a partly natural- and partly human-influenced process.

PMID- 30284616
TI  - Negative covariance between water mite and gregarine parasitism for adult
      dragonflies, Leucorrhinia intacta (Hagen): an age-related pattern?
AB  - Studies on parasite-mediated selection often focus on single parasite taxa
      infecting single species of hosts. However, host populations experience
      infections by multiple parasite taxa simultaneously; coinfection is expected to
      influence how host- and/or parasite-related factors affect host exposure and
      susceptibility to various parasites, and the resulting patterns of infection. We
      sampled adult dragonflies from a population of Leucorrhinia intacta (Hagen) in
      eastern Ontario, Canada. Dragonflies were exposed to parasitism by both water
      mites (Arrenuridae) and gregarines (Eugregarinidae). We tested for covariation
      between these ecto- and endoparasites, while considering potential sex and age
      biases in host sampling and patterns of infection. Mite parasitism differed
      dramatically between host sexes: nearly all collected males were parasitized,
      whereas only half of females were infested. This was likely due to differences in
      age distributions between sexes in sampled dragonflies. Water mite and gregarine
      parasitism showed strong, negative covariation, and coinfection occurred far less
      often than expected by chance, although these patterns were restricted to samples
      of females which, unlike male samples, likely included many old and young
      dragonflies. We report the first observation of negative covariation between
      internal and external parasite taxa in an anisopteran host and suggest this
      relationship between water mites and gregarines may be more widespread among
      Odonata and perhaps other insects than previously surmised. We advance hypotheses
      based on host age-parasitism relationships as well as variable parasite-mediated
      selection to help explain the sex specificity of observed coinfection patterns in
      our samples.

PMID- 30284617
TI  - Clinical significance of hepatic steatosis according to coronary plaque
      morphology: assessment using controlled attenuation parameter.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) plays a significant role in
      coronary atherosclerosis, independent of shared metabolic risk factors. The
      measurement of the controlled attenuation parameter (CAP) has shown to allow
      early and noninvasive detection of NAFLD at subclinical stage. We evaluated the
      significance of CAP-defined NAFLD in association with the presence of any type of
      coronary plaques and different plaque compositions. METHODS: We conducted a
      retrospective cohort of apparently healthy subjects who had liver Fibroscan and
      coronary computed tomography during health screening exams. RESULTS: A greater
      number of subjects with CAP-defined NAFLD was found in group with coronary
      plaques (61.3% vs. 73.5%, p = 0.005 without vs. with any type of plaque). From
      multivariate regression model, CAP >= 222 dB/m was an independent and significant
      parameter associated with the presence of coronary plaques, after adjusting
      possible confounders (OR 1.624, 95% 1.047-2.518, p = 0.030). Interestingly, CAP
      >= 222 dB/m was significantly associated with non-calcified plaque (adjusted OR
      3.528, 95% CI 1.463-8.511, p = 0.005), whereas it was not significant in
      calcified plaques (p = 0.171). CONCLUSION: CAP-defined NAFLD is independently
      associated with coronary plaques, especially non-calcified plaques. The
      association between NAFLD and non-calcified plaques suggests that particular
      attention should be given to the subjects with NAFLD for primary prevention.

PMID- 30284618
TI  - Diabetes mellitus induced by PD-1 and PD-L1 inhibitors: description of pancreatic
      endocrine and exocrine phenotype.
AB  - AIMS: Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1)
      inhibitors restore antitumor immunity, but many autoimmune side-effects have been
      described. Diabetes mellitus is a rare complication, and little data concerning
      its pathophysiology and phenotype have been published. This study aimed to
      describe both pancreatic endocrine and exocrine functions, immunological features
      and change in pancreas volume in subjects with diabetes mellitus induced by PD-1
      and PD-L1 inhibitors. METHODS: We analyzed the data of six subjects treated with
      immunotherapy who presented acute diabetes. RESULTS: There were five men and one
      woman. Median age was 67 years (range 55-83). Three subjects were treated with
      nivolumab, two with pembrolizumab and one with durvalumab. Median time to
      diabetes onset after immunotherapy initiation was 4 months (range 2-13). Four
      patients presented fulminant diabetes (FD); none of these had type 1 diabetes
      (T1D)-related autoantibodies, none of them had T1D or FD-very high-risk HLA class
      II profiles. The bi-hormonal endocrine and exocrine pancreatic failure previously
      reported for one FD patient was not found in other FD subjects, but glucagon
      response was blunted in another FD patient. Pancreas volume was decreased at
      diabetes onset in 2 FD patients, and all patients presented a subsequent decrease
      of pancreas volume during follow-up. CONCLUSIONS: In the patients presented
      herein, immunotherapy-induced diabetes was not associated with T1D-related
      autoantibodies. The hormonal and morphological analysis of the pancreatic glands
      of these six cases contributes to the understanding of the underlying and
      probably heterogeneous mechanisms. There is a need to find biomarkers to identify
      patients at risk to develop these new forms of diabetes at early stages of the
      process to prevent ketoacidosis and to evaluate preventive strategies.

PMID- 30284619
TI  - Glyphosate induces the synthesis of ppGpp.
AB  - Glyphosate, the most widely used herbicide in both agricultural and urban areas
      is toxic for plants and for many bacterial species. The mechanism of action of
      glyphosate is through the inhibition of the EPSP synthase, a key enzyme in the
      biosynthetic pathway of aromatic amino acids. Here we show that glyphosate
      induces the stringent response in Escherichia coli. Bacteria treated with
      glyphosate stop growing and accumulate ppGpp. Both growth arrest and ppGpp
      accumulation are restored to normal levels upon addition of aromatic amino acids.
      Glyphosate-induced ppGpp accumulation is dependent on the presence of the
      (p)ppGpp synthetase RelA. However, unlike other cases of amino acid starvation,
      pppGpp could not be discerned. In a gppA background both ppGpp and pppGpp
      accumulated when exposed to glyphosate. Conversely, the wild-type strain and gppA
      mutant treated with serine hydroxamate accumulated high levels of both ppGpp and
      pppGpp. Altogether, the data indicate that glyphosate induces amino acid
      starvation resulting in a moderate accumulation of ppGpp and a reversible
      stringent response.

PMID- 30284620
TI  - Disadvantages of a weight estimation formula for macrosomic fetuses: the Hart
      formula from a clinical perspective.
AB  - PURPOSE: Sonographic fetal weight (FW) estimation to detect macrosomic fetuses is
      an essential part of everyday routine work in obstetrics departments. Most of the
      commonly used weight estimation formulas underestimate FW when the actual birth
      weight (BW) exceeds 4000 g. One of the best-established weight estimation
      formulas is the Hadlock formula. In an effort to improve the detection rates of
      macrosomic infants, Hart et al. published a specially designed formula including
      maternal weight at booking. The usefulness of the Hart formula was tested.
      METHODS: Retrospective study of 3304 singleton pregnancies, birth weight >= 3500
      g. The accuracy of the Hadlock and Hart formula were tested. A subgroup analysis
      examined the influence of the maternal weight. The Chi-squared test and one-way
      analysis of variation were carried out. For all analyses, p < 0.05 was considered
      statistically significant. RESULTS: The overall percentages of births falling
      within +/- 5% and +/- 10% of the BW using the Hadlock formula were 27% and 53%,
      respectively. Using the Hart formula, 24% and 54% were identified within these
      levels. With the Hart formula, 94% of all weight estimations fall within 4200 g
      +/- 5% and nearly 100% fall within 4200 g +/- 10%. CONCLUSIONS: Applying the Hart
      formula results in an overestimation of fetal weight in neonates with a birth
      weight < 4000 g and fails to identify high-risk fetuses. We, therefore, do not
      consider Hart's formula to be of clinical relevance.

PMID- 30284621
TI  - The differences in placental pathology and neonatal outcome in singleton vs. twin
      gestation complicated by small for gestational age.
AB  - OBJECTIVE: We aimed to compare placental histopathology and neonatal outcome
      between dichorionic diamniotic (DCDA) twins and singleton pregnancies complicated
      by small for gestational age (SGA). METHODS: Medical files and placental
      pathology reports from all deliveries between 2008 and 2017 of SGA neonates,
      (birthweight < 10th percentile), were reviewed. Comparison was made between
      singleton pregnancies complicated with SGA (singletons SGA group) and DCDA twin
      pregnancies (Twins SGA group), in which only one of the neonates was SGA.
      Placental diameters were compared between the groups. Placental lesions were
      classified into maternal and fetal vascular malperfusion lesions (MVM and FVM),
      maternal (MIR) and fetal (FIR) inflammatory responses, and chronic villitis.
      Neonatal outcome parameters included composite of early neonatal complications.
      RESULTS: The twins SGA group (n = 66) was characterized by a higher maternal age
      (p = 0.011), lower gestational age at delivery (34.9 +/- 3.1 vs. 37.7 +/- 2.6
      weeks, p < 0.001), and a higher rate of preeclampsia (p = 0.010), compared to the
      singletons SGA group (n = 500). Adverse composite neonatal outcome was more
      common in the twins SGA group (p < 0.001). Placental villous lesions related to
      MVM (p < 0.001) and composite MVM lesions (p = 0.04) were more common in the
      singletons SGA group. On multivariate logistic regression analysis, the
      singletons SGA group was independently associated with placental villous lesions
      (aOR 3.6, 95% CI 1.9-7.0, p < 0.001) and placental MVM lesions (aOR 2.44, 95% CI
      1.29-4.61, p = 0.006). CONCLUSION: Placentas from SGA singleton pregnancies have
      more MVM lesions as compared to placentas from SGA twin pregnancies, suggesting
      different mechanisms involved in abnormal fetal growth in singleton and twin
      gestations.

PMID- 30284622
TI  - [Tobacco prevention using the example of the "smoke-free" campaign : Nationwide
      measures by the Federal Center for Health Education (BZgA)].
AB  - Currently, 28.7% of 18- to 64-year-olds in Germany smoke (26.1% of women/31.2% of
      men). Among the 12- to 17-year-olds, the smoking rate at 7.4%, is at a historic
      low. The smoking rate among the 18- to 25-year-olds has also fallen in recent
      years.The most important goal of the nationwide measures of the Federal Center
      for Health Education (BZgA) on tobacco prevention is to reduce the smoking rate.
      For this purpose, the BZgA carries out the "smoke-free" campaign, which is
      targeted at both adolescents and adults. With a closely interlinked and
      continuously reviewed and further developed mix of measures, the target groups
      are reached on the internet, in settings and via media and mass communication. In
      addition to the information on the risks of smoking and passive smoking, the
      motivation to quit smoking and the quality-assured support in smoking cessation
      play an important role here.The measures of the BZgA are reviewed and further
      developed on the basis of representative surveys on the smoking behavior of the
      12- to 25-year-olds, which the BZgA regularly carries out. On this basis, new
      products, such as e-cigarettes, e-shishas or tobacco heaters, and new consumer
      trends, such as the trend for waterpipe smoking, are integrated. Access routes to
      the target groups are continuously reviewed against the background of the
      digitization of society and the health-promoting design of settings is supported.
      All in all, the smoke-free campaign offers a quality-assured range of measures
      that is continuously being developed.

PMID- 30284624
TI  - ["Heat not burn" tobacco devices as new tobacco industry products: health risks].
AB  - Increased tobacco control measures in recent years have directed the tobacco
      industry to develop alternative tobacco products, such as "heat not burn" (HnB)
      tobacco devices that are implied to be less hazardous than conventional
      cigarettes. There are extensive studies from manufacturers available, which show
      that the emissions of HnB tobacco devices have significantly lower levels of
      harmful substances compared to conventional cigarettes. In addition,
      manufacturers have published studies to investigate whether switching from a
      conventional tobacco cigarette to the HnB product reduces possible health
      risks.The purpose of this report is to review current studies by manufacturers
      and independent institutions as well as to discuss possible reduced health
      hazards.The German Federal Institute for Risk Assessment (BfR) has carried out
      its own studies of selected analytes in the emissions of one HnB product
      confirming the lower levels of harmful substances in the emissions. The results
      are consistent with data from other independent studies. The nicotine content in
      the emissions is in the same range as the nicotine emissions of conventional
      cigarettes, which suggests a comparable addictiveness and dependence potential.
      Manufacturers have reported mutagenic effects of emissions by HnB tobacco devices
      that, however, are considerably weaker compared to conventional cigarettes.
      Nevertheless, the use of the HnB tobacco product remains associated with health
      risks.Switching from conventional cigarettes to tobacco heaters can significantly
      reduce the consumer's exposure to harmful substances. However, this article also
      illustrates that it is still unclear to what extent the reduced levels lead to
      lowered health risks. Therefore more independent studies, but also long-term
      studies, are needed.

PMID- 30284623
TI  - [The global medical network Education Against Tobacco-voluntary tobacco
      prevention made in Germany].
AB  - Smoking is the leading preventable cause of premature death in Germany. The
      network "Education Against Tobacco" (EAT) is an initiative that was founded in
      Germany in 2012, in which more than 3500 medical students and physicians engage
      in volunteer work in about 80 medical faculties in 14 countries. In this article,
      the concept, activities, objectives and associated research studies oft he EAT
      initiative are introduced.On the school level, the initiative addresses 10- to 15
      year-old secondary school students. In addition to a multimodal approach, school
      visits use modern media such as facemorphing apps, which are not only used by
      students (45,000 per year in 14 countries), but by a total of over 500,000 other
      people as well. The effectiveness of the school-based intervention is currently
      being investigated in randomised long-term studies with 20,000 adolescents in
      Germany. A first long-term study demonstrated evidence of a protective effect
      regarding the onset of smoking, especially among female students, students having
      a low level of education and students with a migratory background.The programme
      educates several hundred prospective physicians at 13 (of 28 participating)
      German medical faculties each year in science-based elective courses for the well
      established smoking cessation counselling of patients and sensitises them to the
      tobacco epidemic. The approved members engage in dialogue with local members of
      the German house of representatives as "Arzteverband Tabakpravention".EAT
      motivates the prospective generation of physicians, initially through prevention
      in school settings, to face the challenge of national tobacco control at the
      university and federal level.

PMID- 30284625
TI  - [E-cigarettes: Perceived harmfulness and use for smoking cessation].
AB  - BACKGROUND: The perception that e-cigarettes are less harmful than traditional
      tobacco products can influence the consumption of e-cigarettes. OBJECTIVES: Three
      questions were examined: (1) How do different population groups perceive health
      risks of e-cigarettes? (2) Do sociodemographic variables explain differences in
      the risk assessment of e-cigarettes? (3) Does the perception of health risks
      predict the use of e-cigarettes for smoking cessation? METHODS: Data came from
      the 2015 Epidemiological Survey of Substance Abuse (ESA) with a sample size of n
      = 9204 participants, aged 18 to 64 years (response rate 52.2%). Data were
      collected by telephone, online, or by written questionnaires. Assessments of risk
      perception of e-cigarettes and conventional cigarettes (more harmful, just as
      harmful, less harmful, do not know) were compared. Descriptive statistics and
      logistic regressions were performed. RESULTS: Individuals with lower education
      rated e-cigarettes as more harmful. Older people and women perceived e-cigarettes
      as just as harmful. Smokers considered e-cigarettes to be more harmful than or
      just as harmful as conventional tobacco products. The likelihood of using e
      cigarettes for smoking cessation was higher if people thought they were less
      harmful than conventional cigarettes. CONCLUSIONS: Only one-third of the
      population knows that e-cigarettes are less harmful to health than conventional
      cigarettes. The perception of health risks is related to the usage of e
      cigarettes for smoking cessation.

PMID- 30284626
TI  - [E-cigarettes and heat-not-burn products: representative data on consumer
      behaviour and associated factors in the German population (the DEBRA study)].
AB  - BACKGROUND: Electronic cigarettes (ECs) and heat-not-burn (HNB) devices are
      relatively new products that are increasingly used alternatively or complementary
      to ordinary tobacco products. OBJECTIVES: To analyse current data from the German
      Study on Tobacco Use (DEBRA) regarding the prevalence of EC and HNB device use
      and associated socioeconomic factors and smoking behaviour; compare reasons for
      EC use between adolescents and adults; describe the self-perceived risk of HNB
      devices. MATERIAL AND METHODS: DEBRA is an ongoing, representative, face-to-face
      household survey of the population aged 14 years and older. We analysed data from
      the first nine waves (June/July 2016 to October/November 2017; n = 18,415) for
      the current study. RESULTS: During the observation period, 1.9% (95% confidence
      interval (CI) = 1.7-2.2%) of the German population used ECs (2.8% of the 14- to17
      year-olds) and 74.5% (95% CI = 69.4-79.2%) of current EC users also smoked
      tobacco ("dual use"). Three-quarters of adolescents used ECs mainly "for fun",
      whereas reasons for use among adults related more to smoking tobacco (e. g., less
      harmful, to quit smoking). Among current smokers and recent ex-smokers (<12
      months smoke-free), 0.3% (95% CI = 0.09-0.64%) currently used HNB devices, and
      6.0% (95% CI = 5.0-7.2%) had ever used them. Consumption of HNB products
      increased with increasing education and income. The majority perceived HNB
      products as somewhat (41.0%, n = 25) or much (14.8%, n = 9) less harmful, and
      37.7% (n = 23) as equally harmful compared with tobacco cigarettes. CONCLUSIONS:
      In Germany, ECs are mainly consumed as "dual use" together with tobacco.
      Consumption of HNB products currently occurs at a very low rate and is relatively
      more common among smokers with higher education and income. It remains important
      to monitor the use of new electronic inhalation products in the total population
      and in relevant subgroups.

PMID- 30284627
TI  - Thailand orthohantavirus infection in patients with chronic kidney disease of
      unknown aetiology in Sri Lanka.
AB  - Chronic kidney disease of unknown aetiology (CKDu) reported in Sri Lanka and
      other countries is a mysterious and serious disease. Recently, we reported a high
      seroprevalence of antibodies to a hantavirus antigen among CKDu patients in
      Girandurukotte, Badulla district, Sri Lanka. However, the type of hantavirus with
      which the residents were infected was not determined. In this study, a total of
      89 seropositive sera were examined to identify their serotypes using an indirect
      immunofluorescent antibody assay, a truncated-N-protein-based enzyme-linked
      immunosorbent assay, and a cross-neutralization test. These results indicated
      that the residents in this area were frequently infected with Thailand
      orthohantavirus or an antigenically related virus.

PMID- 30284628
TI  - The influence of porcine epidemic diarrhea virus on pig small intestine mucosal
      epithelial cell function.
AB  - Porcine epidemic diarrhea (PED) is a highly contagious, acute enteric tract
      infectious disease of pigs (Sus domesticus) caused by porcine epidemic diarrhea
      virus (PEDV). PED is characterized by watery diarrhea, dehydration, weight loss,
      vomiting and death. PEDV damages pig intestinal epithelial tissue, causing
      intestinal hyperemia and atrophy of intestinal villi, with formation of
      intestinal epithelial cell cytoplasmic vacuoles. Since pig small intestinal
      epithelial cells (IECs) are target cells of PEDV infection, IEC cells were
      utilized as a model for studying changes in cellular activities post-PEDV
      infection. Monitoring of Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities
      demonstrated that PEDV infection decreased these activities. In addition, IECs
      proliferation was shown to decrease after PEDV infection using an MTT assay.
      Moreover, IECs apoptosis detected by flow cytometry with propidium iodide (PI)
      staining was clearly shown to increase relative to the control group. Meanwhile,
      animal experiments indicated that PEDV virulence for IEC cells was greater than
      viral virulence for Vero cells, although this may be due to viral attenuation
      after numerous passages in the latter cell line. Collectively, these studies
      revealed viral pathogenic mechanisms in PEDV-infected IECs and offer a
      theoretical basis for PEDV prevention and control.

PMID- 30284629
TI  - Kaposi sarcoma-associated herpes virus (KSHV) latent protein LANA modulates
      cellular genes associated with epithelial-to-mesenchymal transition.
AB  - Kaposi's sarcoma-associated herpes virus (KSHV) is a gammaherpesvirus associated
      with Kaposi's sarcoma and various lymphoproliferative diseases. Epithelial-to
      mesenchymal transition (EMT) is an important step in the metastasis of cancer
      cells. Previous studies have shown an important role for EMT markers in B-cell
      malignancies. In the present study, we investigated the role of the KSHV latent
      protein LANA in the progression of EMT. Our data suggest that expression of LANA
      results in an increase in the migration and invasion potential of cancer cells,
      which is concurrent with modulation of transcriptional regulation and protein
      expression of several cellular genes associated with EMT. LANA expression results
      in upregulation of the cellular intermediate filament protein vimentin and
      transcription factor TCF8/ZEB1 and downregulation of tight junction protein ZO1
      and adhesion protein E-cadherin. LANA co-localizes with TCF8/ZEB1, a major
      contributor in EMT, further suggesting an important role for LANA in epithelial
      to-mesenchymal transition of KSHV-infected cancer cells.

PMID- 30284630
TI  - The complete genome sequence analysis of West Nile virus strains isolated in
      Slovakia (central Europe).
AB  - The present study reports the first complete genome sequence analysis of West
      Nile virus (WNV) strains isolated from brain samples from raptors. The results
      prove the circulation of closely related WNV lineage II strains in central Europe
      and genetic analysis revealed seven amino acid substitutions in structural (PrM3,
      E159 and E231) and in non-structural (NS1109, NS5259, NS5310 and NS5600)
      proteins. Observed amino acid substitutions Phe3 and Ser231 were common only
      within the lineage VII Koutango strain isolated from Rhipicephalus guilhoni tick
      in Senegal. Further research could reveal whether these substitutions influence
      the biological properties of WNV, including virulence and neuroinvasiveness.

PMID- 30284631
TI  - GI.1b/GI.1b/GI.2 recombinant rabbit hemorrhagic disease virus 2 (Lagovirus
      europaeus/GI.2) in Morocco, Africa.
AB  - Rabbit hemorrhagic disease virus (RHDV) is highly lethal to the European rabbit
      (Oryctolagus cuniculus). It was first reported in 1984 in China, but in 2010, a
      new variant of the virus was detected (GI.2) in France. Several recombination
      events with pathogenic and non-pathogenic strains have been described. Here, we
      report the first sequences of RHDV in Africa, isolated from Moroccan rabbits, and
      these resemble GI.1b/GI.1b/GI.2 recombinants found in the Iberian Peninsula.
      Monitoring and characterization of strains from future outbreaks are advised to
      guarantee the success of current programs on small-rabbit production for poverty
      alleviation in African countries.

PMID- 30284632
TI  - Isolation, identification, and classification of a novel rhabdovirus from
      diseased Chinese rice-field eels (Monopterus albus).
AB  - In 2017, a clinical disease outbreak resulted in substantial mortality of adults
      and larvae of cultured Chinese rice-field eels (Monopterus albus) on a farm in
      Hubei, Central China. A rhabdovirus was isolated from moribund specimens, and
      typical clinical symptoms associated with an outbreak included an enlarged and
      swollen head. This differed from previous observations. Histological changes
      included necrosis and cavities of various sizes within the brain and kidney.
      Homogenized tissues of diseased Chinese rice-field eels were screened for viral
      isolation using six different fish cell lines. A rhabdovirus was isolated
      following observation of cytopathic effect (CPE) in a gibel carp brain (GiCB)
      cell line and confirmed by RT-PCR. Electron microscopy showed large numbers of
      rhabdovirus-shaped particles in the cytoplasm of the brain cells of the diseased
      Chinese rice-field eels and in the infected GiCB cell line. This virus has been
      named "Chinese rice-field eel rhabdovirus" (CrERV), and the complete nucleotide
      sequence of CrERV was cloned. This rhabdovirus is composed of 11,545 nucleotides
      with the following genomic organization: 3'-N-P-M-G-L-5'. The genes are separated
      by conserved gene junctions, and phylogenetic analysis of the L sequence revealed
      that CrERV forms a separate branch with Siniperca chuatsi rhabdovirus (SCRV) and
      hybrid snakehead rhabdovirus C1207 (HSHRV-C1207). This is the first report of the
      complete sequence of CrERV from the Chinese rice-field eel in China.

PMID- 30284633
TI  - The man from room number seven.

PMID- 30284634
TI  - Do not abandon monitoring the central venous pressure during fluid resuscitation
      of septic shock patients.

PMID- 30284635
TI  - Frugal innovation for critical care.

PMID- 30284636
TI  - Cardiovascular focus editorial ICM 2018.

PMID- 30284638
TI  - Dark urine, hypotension and blood smear examination.

PMID- 30284639
TI  - What's new in electrical impedance tomography.

PMID- 30284637
TI  - Challenges in assessing the burden of sepsis and understanding the inequalities
      of sepsis outcomes between National Health Systems: secular trends in sepsis and
      infection incidence and mortality in Germany.
AB  - PURPOSE: Sepsis contributes considerably to global morbidity and mortality, while
      reasons for its increasing incidence remain unclear. We assessed risk adjusted
      secular trends in sepsis and infection epidemiology in Germany. METHODS:
      Retrospective cohort study using nationwide German hospital discharge data. We
      assessed incidence, outcomes and trends of hospital-treated sepsis and infections
      between 2010 and 2015. Sepsis was identified by explicit ICD-10 sepsis codes. As
      sensitivity analysis, results were compared with sepsis cases identified by
      implicit sepsis coding (combined infection and organ dysfunction codes). RESULTS:
      Among 18 664 877 hospital admissions in 2015, 4 213 116 (22.6%) patients had at
      least one infection code. There were 320 198 patients that had explicit sepsis
      codes including 136 542 patients with severe sepsis and septic shock; 183 656
      patients were coded as sepsis without organ dysfunction. For patients with
      explicitly coded sepsis (including severe sepsis), or with severe sepsis alone,
      mortality rates over the period 2010-2015 decreased from 26.6 to 23.5%, and from
      47.8 to 41.7%, respectively. CONCLUSIONS: Sepsis and infection remain significant
      causes of hospital admission and death in Germany. Sepsis-related mortality is
      higher and has declined to a lesser degree than in other high-income countries.
      Although infection rates steadily increased, the observed annual increase of
      sepsis cases seems to result, to a considerable degree, from improved coding of
      sepsis.

PMID- 30284640
TI  - Will my patient survive? Look for creatinine in the urine!

PMID- 30284641
TI  - High diversity of thermophilic cyanobacteria in Rupite hot spring identified by
      microscopy, cultivation, single-cell PCR and amplicon sequencing.
AB  - Genotypic and morphological diversity of cyanobacteria in the Rupite hot spring
      (Bulgaria) was investigated by means of optical microscopy, cultivation, single
      cell PCR, and 16S rRNA gene amplicon sequencing. Altogether, 34 sites were
      investigated along the 71-39  degrees C temperature gradient. Analysis of samples
      from eight representative sites shown that Illumina, optical microscopy, and
      Roche 454 identified 72, 45 and 19% respective occurrences of all cumulatively
      present taxa. Optical microscopy failed to detect species of minor occurrence;
      whereas, amplicon sequencing technologies suffered from failed primer annealing
      and the presence of species with extensive extracellular polysaccharides
      production. Amplicon sequencing of the 16S rRNA gene V5-V6 region performed by
      Illumina identified the cyanobacteria most reliably to the generic level.
      Nevertheless, only the combined use of optical microscopy, cultivation and
      sequencing methods allowed for reliable estimate of the cyanobacterial diversity.
      Here, we show that Rupite hot-spring system hosts one of the richest
      cyanobacterial flora reported from a single site above 50  degrees C.
      Chlorogloeopsis sp. was the most abundant at the highest temperature (68  degrees
      C), followed by Leptolyngbya boryana, Thermoleptolyngbya albertanoae,
      Synechococcus bigranulatus, Oculatella sp., and Desertifilum sp. thriving above
      60  degrees C, while Leptolyngbya geysericola, Geitlerinema splendidum, and
      Cyanobacterium aponinum were found above 50  degrees C.

PMID- 30284642
TI  - Low CT temporal sampling rates result in a substantial underestimation of
      myocardial blood flow measurements.
AB  - The purpose of this study was to evaluate the effect of temporal sampling rate in
      dynamic CT myocardial perfusion imaging (CTMPI) on myocardial blood flow (MBF).
      Dynamic perfusion CT underestimates myocardial blood flow compared to PET and
      SPECT values. For accurate quantitative analysis of myocardial perfusion with
      dynamic perfusion CT a stable calibrated HU measurement of MBF is essential.
      Three porcine hearts were perfused using an ex-vivo Langendorff model.
      Hemodynamic parameters were monitored. Dynamic CTMPI was performed using third
      generation dual source CT at 70 kVp and 230-350 mAs/rot in
      electrocardiography(ECG)-triggered shuttle-mode (sampling rate, 1 acquisition
      every 2-3 s; z-range, 10.2 cm), ECG-triggered non-shuttle mode (fixed table
      position) with stationary tube rotation (1 acquisition every 0.5-1 s, 5.8 cm),
      and non-ECG-triggered continuous mode (1 acquisition every 0.06 s, 5.8 cm).
      Stenosis was created in the circumflex artery, inducing different fractional flow
      reserve values. Volume perfusion CT Myocardium software was used to analyze ECG
      triggered scans. For the non-ECG triggered scans MASS research version was used
      combined with an in-house Matlab script. MBF (mL/g/min) was calculated for non
      ischemic segments. True MBF was calculated using input flow and heart weight.
      Significant differences in MBF between shuttle, non-shuttle and continuous mode
      were found, with median MBF of 0.87 [interquartile range 0.72-1.00], 1.20 (1.07
      1.30) and 1.65 (1.40-1.88), respectively. The median MBF in shuttle mode was 56%
      lower than the true MBF. In non-shuttle and continuous mode, the underestimation
      was 41% and 18%. Limited temporal sampling rate in standard dynamic CTMPI
      techniques contributes to substantial underestimation of true MBF.

PMID- 30284643
TI  - In vitro leishmanicidal activity and theoretical insights into biological action
      of ruthenium(II) organometallic complexes containing anti-inflammatories.
AB  - Leishmaniasis, a neglected tropical disease caused by protozoans of the genus
      Leishmania, kills around 20-30 thousand people in Africa, Asia, and Latin America
      annually and, despite its potential lethality, it can be treated and eventually
      cured. However, the current treatments are limited owing to severe side effects
      and resistance development by some Leishmania. These factors make it urgent to
      develop new leishmanicidal drugs. In the present study, three ruthenium(II)
      organometallic complexes containing as ligands the commercially available anti
      inflammatories diclofenac (dic), ibuprofen (ibu), and naproxen (nap) were
      synthesized, characterized, and subjected to in vitro leishmanicidal activity.
      The in vitro cytotoxicity assays against Leishmania (L.) amazonensis and
      Leishmania (L.) infantum promastigotes have shown that complexes [RuCl(dic)(eta6
      p-cymene)] (1) and [RuCl(nap)(eta6-p-cymene)] (3) were active against both
      Leishmania species. Complex [RuCl(ibu)(eta6-p-cymene)] (2) has exhibited no
      activity. The IC50 values for the two active complexes were respectively 7.42 and
      23.55 MUM, for L. (L.) amazonensis, and 8.57 and 42.25 MUM, for L. (L.) infantum.
      Based on the toxicological results and computational analysis, we proposed a
      correlation between the complexes and their activity. Our results suggest both
      complexation to ruthenium(II) and ligands structure are key elements to
      leishmanicidal activity.

PMID- 30284644
TI  - Chromosomal Sil system contributes to silver resistance in E. coli ATCC 8739.
AB  - The rise of antibiotic resistance in pathogenic bacteria is endangering the
      efficacy of antibiotics, which consequently results in greater use of silver as a
      biocide. Chromosomal mapping of the Cus system or plasmid encoded Sil system and
      their relationship with silver resistance was studied for several gram-negative
      bacteria. However, only few reports investigated silver detoxification mediated
      by the Sil system integrated in Escherichia coli chromosome. Accordingly, this
      work aimed to study the Sil system in E. coli ATCC 8739 and to produce evidence
      for its role in silver resistance development. Silver resistance was induced in
      E. coli ATCC 8739 by stepwise passage in culture media containing increasing
      concentrations of AgNO3. The published genome of E. coli ATCC 8739 contains a
      region showing strong homology to the Sil system genes. The role of this region
      in E. coli ATCC 8739 was assessed by monitoring the expression of silC upon
      silver stress, which resulted in a 350-fold increased expression. De novo
      sequencing of the whole genome of a silver resistant strain derived from E. coli
      ATCC 8739 revealed mutations in ORFs putative for SilR and CusR. The silver
      resistant strain (E. coli AgNO3R) showed constitutive expression of silC which
      posed a cost of fitness resulting in retarded growth. Furthermore, E. coli AgNO3R
      exhibited cross-resistance to ciprofloxacin and a slightly increased tolerance to
      ampicillin. This study demonstrates that E. coli is able to develop resistance to
      silver, which may pose a threat towards an effective use of silver compounds as
      antiseptics.

PMID- 30284646
TI  - Imbalance of circulating Tfr/Tfh ratio in patients with rheumatoid arthritis.
AB  - Follicular helper T(Tfh) cells and follicular regulatory T(Tfr) cells are
      critical for the development and maintenance of germinal center and humoral
      immune responses. Accumulating evidence has demonstrated that the dysregulation
      of either Tfh or Tfr cells contributes to the pathogenesis of autoimmune
      diseases. The aim of this study was to examine the numbers of Tfh and Tfr cells
      in patients with rheumatoid arthritis (RA). Twenty-four patients with RA patients
      and 20 health controls (HCs) were enrolled in this study. We analyzed the numbers
      of Tfh (CD4+ CXCR5+ PD-1hi) cells and Tfr (CD4+ CXCR5+CD127lo) cells in 24 RA
      patients via flow cytometry. The level of the soluble PD-1 and its ligands (sPD
      L1 and sPDL-2) were examined by ELISA. Flow cytometry revealed that both
      circulating Tfh and Tfr cells were increased in RA patients compared with HCs.
      More importantly, the ratio of Tfr/Tfh was decreased, indicating a disruption of
      the balance between Tfh and Tfr. The Tfr/Tfh ratio was inversely correlated with
      level of serum CRP, ESR, RF, anti-CCP, IgG and DAS28 index. We also found that
      the serum level of sPD-1 was significantly elevated in the RA patients, which was
      positively correlated with CRP, ESR and the number of Tfh cells. These results
      indicate that an imbalance of circulating Tfr and Tfh cells may be involved in
      the immunopathogenesis of RA and may provide novel insight for the development of
      RA therapies.

PMID- 30284645
TI  - App-Based Insulin Calculators: Current and Future State.
AB  - PURPOSE OF REVIEW: To perform a comprehensive literature review and critical
      assessment of peer-reviewed manuscripts addressing the efficacy, safety, or
      usability of insulin calculator apps. RECENT FINDINGS: Managing diabetes with
      insulin can be complex, and literacy and numeracy skills pose barriers to manual
      insulin dose calculations. App-based insulin calculators are promising tools to
      help people with diabetes administer insulin safely and have potential to improve
      glycemic control. While a large number of apps which assist with insulin dosing
      are available, there is limited data evaluating their efficacy, safety, and
      usability. Recently, a need for regulatory oversight has been recognized, but few
      apps meet federal standards. Thus, choosing an appropriate app is challenging for
      both patients and providers. An electronic literature review was performed to
      identify insulin calculator apps with either evidence for efficacy, safety or
      usability published in peer-reviewed literature or with FDA/CE approval. Twenty
      apps were identified intended for use by patients with diabetes on insulin. Of
      these, nine included insulin calculators. Summaries of each app, including pros
      and cons, are provided. Insulin-calculator apps have the potential to improve
      self-management of diabetes. While current literature demonstrates improvements
      in quality of life and glycemic control after use of these programs, larger
      trials are needed to collect outcome and safety data. Also, further human factor
      analysis is needed to assure these apps will be adopted appropriately by people
      with diabetes. App features including efficacy and safety data need to be easily
      available for consumer review and decision making. Higher standards need to be
      set for app developers to ensure safety and efficacy.

PMID- 30284647
TI  - Volumetric modulated arc therapy (VMAT) in the treatment of esophageal cancer
      patients.
AB  - The aim of the study is to evaluate feasibility, safety, toxicity profile, and
      dosimetric results of volumetric modulated arc therapy (VMAT) to deliver
      definitive or pre-operative radiation in locally advanced esophageal cancer
      patients. A total of 68 patients were treated with VMAT between March 2014 and
      March 2018 (44% vs 56% for definitive and neoadjuvant settings, respectively).
      Dose prescription differed depending on the clinical scenario (54-60 Gy in 30
      fractions for definitive treatments; 41.4/45 Gy in 23-25 fractions in the pre
      operative setting). Most of the patients were given concurrent chemotherapy. Two
      coplanar and one non-coplanar arcs were employed for VMAT delivery. Treatment was
      generally well tolerated. Acute toxicity was generally mild. In patients treated
      with definitive intent, >= G3 toxicities were observed for esophagitis (30%),
      anorexia (26.7%), fatigue (26.7%), nausea (6.7%), and vomiting (3.3%). In
      patients treated within a neoadjuvant approach, >= G3 anorexia (21%), esophagitis
      (15.8%), fatigue (13.3%), nausea (5.3%), and vomiting (2.6%) were observed.
      Dosimetric results were consistent in term of both target coverage and normal
      tissue sparing. In conclusion, VMAT proved to be a feasible, safe, and effective
      strategy to deliver definitive or pre-operative radiation in locally advanced
      esophageal cancer patients.

PMID- 30284649
TI  - The use of radiofrequency ablation in pancreatic cancer in the midst of the dawn
      of immuno-oncology.
AB  - Despite significant improvement in treatment, the prognosis of pancreatic ductal
      adenocarcinoma remains poor as the biology of the tumour affects survival even
      when a radical resection has been performed. Pancreatic cancer remains resistant
      to currently available chemotherapeutic options. Recently, immunotherapy has
      achieved significant results in certain types of cancer. However, for pancreatic
      cancer, results were not initially encouraging as pancreatic cancer
      microenvironment is highly immunosuppressive. Radiofrequency ablation is
      currently used as treatment option especially for liver cancer with significant
      results. However, in pancreatic cancer, the use of radiofrequency ablation is
      relatively new. Radiofrequency ablation has been identified as a promising
      mechanism to induce antigen-presenting cell infiltration and enhance systemic
      antitumour T-cell immune response and tumour regression. In this short
      communication, we briefly review the role of radiofrequency ablation in
      pancreatic cancer and explore the idea that the combination of radiofrequency
      ablation with immunotherapy could represent a novel and promising treatment.

PMID- 30284650
TI  - Perspectives on the role of brain cellular players in cancer-associated brain
      metastasis: translational approach to understand molecular mechanism of tumor
      progression.
AB  - Brain metastasis is one of the leading causes of death among cancer patients.
      Cancer cells migrate to various sites and harbor different niche in the body
      which help cancer cells in their survival. The brain is one of the safest place
      where cancer cells are protected from immune cells. Breast, lung, and melanoma
      cancer cells have high propensity to migrate towards the brain. To enter the
      brain, cancer cells have to cross the blood brain barrier. Survival and finding
      new niche in the brain are directed by several mechanisms in which different
      cellular players take part such as astrocytes, microglia, Schwann cells,
      satellite cells, oligodendrocytes, and ependymal cells. Usually, cancer cells
      highjack the machinery of brain cellular players to survive in the brain
      environment. It has been shown that co-culture of M2 macrophage with cancer cells
      leads to increased proliferation and survival of cancer cells. One of the
      challenges of understanding brain metastasis is appropriate model system to
      understand dynamic interaction of cancer cells and brain cellular players. To
      meet this challenge, microfluidic-based devices are employed which can mimic the
      dynamic conditions as well as can be used for culturing human cells for
      personalized therapy. In this review, we have systematically reviewed the current
      status of the role of cellular players in brain metastasis along with explaining
      how translational approach of microfluidics can be employed for finding new drug
      target as well as biomarker for brain metastasis. Finally, we have also commented
      on the mechanism of action of drugs against brain metastasis.

PMID- 30284648
TI  - Biotechnological potential of plant growth-promoting bacteria from the roots and
      rhizospheres of endemic plants in ironstone vegetation in southeastern Brazil.
AB  - Microorganisms associated with plants have a great biotechnological potential,
      but investigations of these microorganisms associated with native plants in
      peculiar environments has been incipient. The objective of this study was to
      analyze the plant growth-promoting bacteria potential of cultivable bacteria
      associated with rare plants from the ferruginous rocky fields of the Brazilian
      Iron Quadrangle. The roots and rhizospheres of nine endemic plants species and
      samples of a root found in a lateritiric duricrust (canga) cave were collected,
      the culturable bacteria isolated and prospected for distinct biotechnological and
      ecological potentials. Out of the 148 isolates obtained, 8 (5.4%) showed
      potential to promote plant growth, whereas 4 (2.7%) isolates acted as biocontrol
      agents against Xanthomonas citri pathotype A (Xac306), reducing the cancrotic
      lesions by more than 60% when co-inoculated with this phytopathogen in Citrus
      sinensis plants. Moreover, other 4 (2.7%) isolates were classified as potential
      bioremediation agents, being able to withstand high concentrations of arsenite (5
      mM As3+) and arsenate (800 mM As5+), by removing up to 35% and 15% of this
      metalloid in solution, respectively. These same four isolates had a positive
      influence on the growth of both the roots and the aerial parts when inoculated
      with tomato seeds in the soil contaminated with arsenic. This is the first time
      that an investigation highlights the potentialities of bacteria associated with
      rare plants of ferruginous rocky fields as a reservoir of microbiota of
      biotechnological and ecological interest, highlighting the importance of
      conservation of this area that is undergoing intense anthropic activity.

PMID- 30284651
TI  - Dual Red Imaging Maintains Clear Visibility During Colorectal Endoscopic
      Submucosal Dissection.
AB  - BACKGROUND: The endoscopic lens becomes clouded and its visibility reduces during
      colorectal endoscopic submucosal dissection (ESD), especially in cases with
      submucosal fatty tissue. Dual red imaging (DRI) is a novel image-enhanced
      endoscopic technique that improves endoscopic visibility. AIMS: This study aimed
      to evaluate the predictive factors of submucosal fatty tissue and the clinical
      usefulness of DRI in maintaining clear visibility during colorectal ESD. METHODS:
      The study participants included 586 consecutive patients with 645 colorectal
      tumors who underwent ESD between January 2014 and July 2017. First, the degree of
      submucosal fatty tissue was evaluated by reviewing recorded images, and the
      clinical characteristics of the patients and tumors related to severe submucosal
      fatty tissue were evaluated. Second, 34 tumors resected using DRI were propensity
      score-matched in a 1:1 ratio to other resected tumors using white light imaging
      (WLI), and the degree of endoscope lens cloudiness and clinical outcomes were
      evaluated. RESULTS: The proportion of tumors located in the right side of the
      colon, body mass index (>= 25, BMI), and hemoglobin A1c (>= 6.5%, HbA1c) were
      significantly higher in patients with severe submucosal fatty tissue. The
      visibility in the DRI group was significantly better than in the WLI group.
      Treatment outcomes in the DRI group were as good as those in the WLI group.
      CONCLUSIONS: Tumor location in the right side of the colon, BMI (>= 25), and
      HbA1c (>= 6.5%) are the predictive factors of severe submucosal fatty tissue. DRI
      is useful in maintaining clear visibility during colorectal ESD, especially with
      submucosal fatty tissue.

PMID- 30284652
TI  - High Trophinin-Associated Protein Expression Is an Independent Predictor of Poor
      Survival in Liver Cancer.
AB  - BACKGROUND: Trophinin-associated protein (TROAP) is a cytoplasmic protein that
      functions as an adhesion molecule in processes such as embryo implantation,
      spindle formation, and cancer. OBJECTIVE: To evaluate the relationship of TROAP
      expression in hepatocellular carcinoma (HCC) tissue with clinicopathologic
      parameters and survival time in liver cancer patients based on an analysis of The
      Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) data. METHODS: RNA
      sequencing (RNA-Seq) expression data and clinical information were downloaded for
      the TCGA-LIHC cohort. Associations between TROAP expression in HCC tissues and
      clinical parameters were evaluated by Chi-square tests. Differences in survival
      between high and low expression groups (median expression cutoff) from Cox
      regression analysis were compared, and P values were calculated by a log-rank
      test. Kaplan-Meier curves were compared with the log-rank test. RESULTS: Analysis
      of RNA-Seq gene expression data for 373 patients with primary tumors revealed
      overexpression of TROAP in liver cancer. High TROAP expression was associated
      with survival status (P = 0.015), T stage (P = 0.049), clinical stage (P =
      0.048), and gender (P = 0.033). Patients with high TROAP-expressing liver cancers
      had a shorter median overall survival of 3.83 years compared with 5.80 years for
      patients with low TROAP-expressing liver cancers (P = 0.00422). Multivariate
      analysis identified TROAP expression as an independent prognostic variable for
      overall survival in liver cancer patients. CONCLUSION: TROAP expression is an
      independent predictor of poor survival in liver cancer.

PMID- 30284654
TI  - Antifungal efficacy of photodynamic therapy with TONS 504 for pathogenic
      filamentous fungi.
AB  - The pathogenic filamentous fungi Fusarium solani (F. solani) and Aspergillus
      fumigatus (A. fumigatus) are common causes of fungal keratitis. We have here
      evaluated the antifungal efficacy of photodynamic antimicrobial chemotherapy
      (PACT) with the novel chlorin derivative TONS 504 and a light-emitting diode
      (LED) with a wavelength of 660 nm for these fungal species. Isolated fungal
      spores were irradiated at LED energies of 10, 20, or 30 J/cm2 in the presence of
      TONS 504 at concentrations of 1 or 10 mg/L. As a control, spores were exposed to
      TONS 504 or LED radiation alone. The treated spores were then cultured on potato
      dextrose agar plates at 25  degrees C for 3 to 4 days before determination of
      colony formation as a measure of viability. Fungal growth was inhibited in a
      manner dependent on both LED energy and TONS 504 concentration. The inhibitory
      effect on F. solani was complete with TONS 504 at a concentration of 1 mg/L and
      LED irradiation at 30 J/cm2 as well as at a TONS 504 concentration of 10 mg/L and
      LED irradiation at 10, 20, or 30 J/cm2. In contrast, that on A. fumigatus was
      only partial at a TONS 504 concentration of 10 mg/L and LED irradiation at 20 or
      30 J/cm2. The antifungal effect of PACT on A. fumigatus was thus inferior to that
      on F. solani. PACT with TONS 504 and an LED thus warrants further evaluation with
      regard to its potential effectiveness for the treatment of infectious fungal
      keratitis.

PMID- 30284653
TI  - High Adherence to HIV Pre-exposure Prophylaxis and No HIV Seroconversions Despite
      High Levels of Risk Behaviour and STIs: The Australian Demonstration Study
      PrELUDE.
AB  - PrELUDE study evaluated daily pre-exposure prophylaxis (PrEP) in high-risk
      individuals in Australia. This open-label, single-arm study tested participants
      for HIV/STI and collected behavioural information three-monthly. We report trends
      over 18 months in medication adherence, side-effects, HIV/STI incidence and
      behaviour. 320 gay/bisexual men (GBM), 4 women and 3 transgender participants,
      followed on average 461 days, reported taking seven pills/week on 1,591 (88.5%)
      occasions and 4-6 pills/week on 153 (8.5%) occasions. No HIV infections were
      observed. STI incidence was high and stable, while gonorrhoea infections declined
      from 100.0 to 25.8/100 person-years between 6 and 15 months (p < 0.001). The
      number of HIV-positive and unknown-status sex partners, and condomless anal
      intercourse, significantly increased. In this high-risk cohort of mainly GBM,
      increases in risk behaviours and high STI incidence were not accompanied by HIV
      infections due to high adherence to daily PrEP. The study informed policy and
      further PrEP implementation among Australian GBM.

PMID- 30284655
TI  - Auditory brainstem response to speech in children with high functional autism
      spectrum disorder.
AB  - Auditory brainstem response (ABR) provides useful information about the auditory
      brainstem pathway. However, there is little known about the subcortical speech
      processing in individuals with autism spectrum disorder (ASD). The aim of the
      present study was to investigate the subcortical speech processing in children
      with high functioning ASD. Twenty-eight children with ASD, with a mean age of
      14.36 +/- 1.86, and 28 typically developing (TD) children, with a mean age of
      14.99 +/- 1.92, were selected from Rofeydeh Rehabilitation Hospital (Tehran,
      Iran), and speech ABR (sABR) with a 40 ms synthetic /da/ syllable stimulus was
      recorded. There was no significant difference between the two groups in terms of
      age and IQ. Latencies of all waves in sABR and duration of V-A complex were
      significantly longer in children with ASD than in TD children. It was concluded
      that patients with ASD have deficits in the temporal neural encoding of speech at
      the brainstem level. Further studies are needed to generalize this result.

PMID- 30284656
TI  - A case of primary angiitis of the central nervous system presenting with diffuse
      cerebral microbleeds and recurrent intracranial hemorrhage.

PMID- 30284657
TI  - Early and rapidly progressing respiratory failure in a patient with amyotrophic
      lateral sclerosis: when FVC% is misleading.

PMID- 30284658
TI  - On the Force-Feeding of Prisoners on Hunger Strike.
AB  - Roughly 80,000 U.S. prisoners are held in solitary confinement at any given time.
      A significant body of research shows that solitary confinement has severe, long
      term effects, and the United Nations has condemned the practice of solitary
      confinement as torture. For years, prisoners have been organizing hunger strikes
      in order to protest solitary confinement. But such action is not without
      consequences, and some inmates have suffered serious injury or death. The
      question I raise in this paper is whether we ought to force-feed hunger striking
      prisoners when serious harm is imminent. Both the World Medical Association and
      the American Medical Association have denounced the practice of force-feeding
      prisoners on hunger strike, and yet, the practice is common. Such prevalence is
      likely a result of the tension between the person-as-patient and person-as
      prisoner and cannot easily be resolved. Instead, we must take seriously the
      complaint that solitary confinement is inhumane and avoid placing health
      professionals in the position where they must choose to force-feed the prisoner
      against his will or not. I argue that a conventional bioethics debate centering
      on polarizing principles of prisoner autonomy and a duty-to-protect the prisoner
      from harm is an inadequate framework for this complex issue. Instead, we must
      examine the prisoner's intent and his right to freedom of speech. I argue that
      when the prisoner's intent is to raise awareness and communicate with others, his
      hunger strike is a form of speech. Protest-as-speech is constitutionally
      protected-even for prisoners-and remains a minimum ethical obligation for society
      to uphold.

PMID- 30284659
TI  - HKUST-1 metal-organic framework for dispersive solid phase extraction of 2-methyl
      4-chlorophenoxyacetic acid (MCPA) prior to its determination by ion mobility
      spectrometry.
AB  - The authors describe a method for the extraction of the herbicide 2-methyl-4
      chlorophenoxyacetic acid (MCPA) from agricultural products. The metal organic
      framework (MOF) HKUST-1 (a copper(II) benzene-1,3,5-tricarboxylate) was used as a
      sorbent for efficient clean-up and preconcentration of MCPA. The effects of pH
      value, stirring time, amount of sorbent on extraction were optimized by central
      composite design. Ultrasonic waves were used for desorption procedure and its
      advantage was demonstrated for an increase in extraction recovery. Corona
      discharge ion mobility spectrometry (IMS) was then applied for fast and sensitive
      determination of MCPA. The method was validated in terms of sensitivity, recovery
      and reproducibility. Under the optimum conditions the calibration plot is linear
      between 0.035-0.200 MUg. L-1. The detection limit is 10 ng L-1, with relative
      standard deviations of <5%. Real samples (water, soil and agricultural product)
      were spiked and then analyzed by this method, and the results revealed efficient
      solid phase extraction and recovery. Graphical abstract Schematic presentation of
      a procedure for extraction of an organochlorine pesticide (2-methyl-4
      chlorophenoxyacetic acid) from agriculture products using the HKUST-1 metal
      organic framework prior to determination by ion mobility spectrometry based on
      its ionization in drift cell.

PMID- 30284660
TI  - Ovarian small cell carcinoma in one of a pair of monozygous twins.
AB  - One of a pair of monozygous twins was diagnosed and died of small cell carcinoma
      of the ovary of hypercalcemic type (SCCOHT) at the age of 30 years. Her sister
      remained unaffected and was very concerned about her risk for developing SCCOHT.
      By performing comprehensive molecular analysis using whole exome sequencing (WES)
      approach, we showed that the deceased twin's tumour has bi-allelic somatic
      genetic defects (a pathogenic frameshift deletion in SMARCA4 and LOH on chr19p).
      Results of WES of constitutional DNA from her unaffected sister were
      confirmatory. Based on our findings, we concluded that the living twin is not at
      risk for SCCOHT and does not need to consider preventive oophorectomy.

PMID- 30284661
TI  - Implantable devices to monitor patients with heart failure.
AB  - Reducing heart failure hospitalizations represents a major challenge for modern
      clinicians. Early detection of congestion plays a key role in disease management
      strategy. Apart from traditional methods (patient reporting symptoms, body weight
      monitoring), novel home-care strategies allow guided adjustments in medical
      therapy through telemonitoring embedded in cardiac electronic implantable devices
      or through stand-alone diagnostic devices for hemodynamic monitoring. Wireless
      pulmonary artery pressure monitoring seems to reduce re-admission risk and is
      currently approved for this purpose in patients with heart failure.
      Multiparameter monitoring is also appealing and could be a valuable tool in
      managing these patients. However, invasive techniques face several safety
      concerns and cost-effectiveness issues. Therefore, quest for future research and
      emerging technologies is necessary.

PMID- 30284662
TI  - Separation of glycosphingolipids with titanium dioxide.
AB  - We introduce the principle of a new technique to isolate glycosphingolipids
      (GSLs) from phospholipids. Neutral and acidic GSLs in organic solvent bind to
      titanium dioxide under neutral pH and can be eluted with 5 mg/ml of 2,5
      dihydroxybenzoic acid in methanol. This special property is applicable for
      eliminating phospholipids, including sphingomyelin, which cannot be eliminated by
      a typical mild alkaline treatment. By using this technique, we demonstrated the
      rapid separation of minor components of GSLs, namely sulfatide and gangliosides
      from rabbit serum and liver, respectively. The minor GSL components were
      effectively purified despite both sources containing tremendous amount of
      phospholipids and simple lipids such as cholesterol, cholesteryl esters and
      triglycerides.

PMID- 30284663
TI  - Neurofeedback Improves Memory and Peak Alpha Frequency in Individuals with Mild
      Cognitive Impairment.
AB  - Mild cognitive impairment (MCI) is a syndrome characterized by a decrease in
      cognitive abilities, while daily function is maintained. This condition, which is
      associated with an increased risk for the development of Alzheimer's disease, has
      no known definitive treatment at present. In this open-label pilot study we
      explored the possible benefits of neurofeedback for subjects with MCI. Eleven
      participants diagnosed with MCI were trained to increase the power of their
      individual upper alpha band of the electroencephalogram (EEG) signal over the
      central parietal region. This was achieved using an EEG-based neurofeedback
      training protocol. Training comprised ten 30-min sessions delivered over 5 weeks.
      Cognitive and electroencephalographic assessments were conducted before and after
      training and at 30 days following the last training session. A dose-dependent
      increase in peak alpha frequency was observed throughout the period of training.
      Memory performance also improved significantly following training, and this
      improvement was maintained at 30-day follow-up, while peak alpha frequency
      returned to baseline at this evaluation. Our findings suggest that neurofeedback
      may improve memory performance in subjects with mild cognitive impairment, and
      this benefit may be maintained beyond the training period.

PMID- 30284664
TI  - Dust distribution in open-pit mines based on monitoring data and fluent
      simulation.
AB  - To understand the concentration and distribution of PM2.5 and PM10 in open-pit
      mines, a beta-ray particle monitor and some laser monitors were arranged in
      Haerwusu Surface Coal Mine (HSCM), Inner Mongolia, China. A fluent simulation was
      made to study the dust move in the pit and escape rate and time out of the pit.
      The main conclusions include (1) in HSCM, the concentration of PM10 changes with
      that of PM2.5, meeting the power function PM10 = 2.548 * PM2.50.993. The dust
      concentration around the working mining equipment is very high. For example,
      around a working drill, the PM2.5 can be up to 426 MUg/m3, and around a working
      power shovel, the PM2.5 can be up to 352 MUg/m3. (2) At the same time, the PM2.5
      concentration is nearly equal throughout the pit, away from the operating
      equipment, with a confidence level of 95%. The mean dust concentration away from
      the equipment is 76.7 MUg/m3 when this mining equipment is working. So, the
      number of monitors in the pit can be decreased without affecting the quality of
      dust monitoring, which means that the cost of monitoring can be cut down. (3)
      Base on Fluent simulation results, the average escape time of dust particles with
      different diameters is similar, but the maximum escape time decreases as the
      particle diameter increases, which means that most dust moves with the air swirl,
      but some smaller dust particles can hang in the pit for a longer time. Also, the
      escape rate decreases rapidly as the diameter of the dust increases. (4) Dust is
      rotated and diffused evenly in the pit under the action of the eddy current in
      the pit. Finally, when the dust is swirled to a higher level than that of the pit
      head, the dust can escape out of the pit.

PMID- 30284666
TI  - College Students' Evaluations and Reasoning About Exclusion of Students with
      Autism and Learning Disability: Context and Goals may Matter More than Contact.
AB  - This study used mixed-effects logistic regression to examine undergraduates' (N =
      142) evaluations and reasoning about scenarios involving disability-based
      exclusion. Scenarios varied by disability [autism spectrum disorder (ASD) versus
      learning disability (LD)], the context of exclusion (classroom versus social),
      and whether or not a grade was at stake. Participants were more likely to
      determine exclusion was acceptable if the excluded student had an ASD diagnosis,
      there was a grade at stake, and it occurred in a classroom. Exclusion was less
      likely to be considered acceptable in the "no grade" compared to the "grade"
      conditions for LD students, but remained high in both conditions for autistic
      students. This study also describes contextual variations in participants'
      justifications for their evaluations.

PMID- 30284667
TI  - Diagnostic and Therapeutic Misconception: Parental Expectations and Perspectives
      Regarding Genetic Testing for Developmental Disorders.
AB  - Parents' understanding/expectations regarding genetic testing for children with
      developmental disorders were explored. Within a month of testing, interviews were
      conducted with 57 parents. Many (74%) could not recall the nature of testing.
      Parents expected genetic testing to have positive impacts for the child (93%) and
      the family (98%), mainly to find the etiology and/or an intervention. Many
      parents (40%) reported not knowing their child's clinical diagnosis. They
      expected genetic testing would establish the diagnosis. Parents anticipated
      potential negative impacts of testing for children (78%) and families (87%),
      mainly finding another illness or not finding potential interventions. Abnormal
      results explaining the disorder were found in 9% of children. In summary, genetic
      results for developmental disorders are unlikely to meet parental expectations.

PMID- 30284668
TI  - 1H, 15N, and 13C resonance assignments of the intrinsically disordered SH4 and
      Unique domains of Hck.
AB  - Hematopoietic cell kinase (Hck) is an important signaling enzyme and a potential
      drug target for HIV infections and Bcr/Abl-chronic myeloid leukemia. The protein
      shares the same SH4-Unique-SH3-SH2-kinase multi-domain architecture as the other
      eight members of the Src family of non-receptor tyrosine kinases. These enzymes
      are often found anchored to the intracellular side of the membrane via lipidation
      of the SH4 domain and are integral components of signaling cascades localized at
      the cell surface. Despite the detailed structural information available for the
      SH3, SH2, and kinase domains of Hck, the intrinsically disordered nature of the
      SH4 and Unique domains has resulted in a lack of information for this important
      region of the protein that is responsible for membrane association. Here, we
      report the 1H, 15N and 13C chemical shifts of the Hck SH4-Unique domains at pH
      4.5.

PMID- 30284669
TI  - Isolation and characterization of a potentially novel Siphoviridae phage
      (vB_SsapS-104) with lytic activity against Staphylococcus saprophyticus isolated
      from urinary tract infection.
AB  - Antibiotic resistance is increasing among Staphylococcus saprophyticus strains
      isolated from urinary tract infection. This necessitates alternative therapies.
      For this, a lytic phage (vB_SsapS-104) against S. saprophyticus, which formed
      round and clear plaques on bacterial culture plates, was isolated from hospital
      wastewater and characterized. Microscopy analysis showed that it had a small head
      (about 50 nm), tail (about 80 nm), and a collar (about 22 nm in length and 19 nm
      in width) indicating to be a phage within Siphoviridae family. Phage vB_SsapS-104
      showed a large latency period of about 40 min, rapid adsorption rate that was
      significantly enhanced by MgCl2 and CaCl2, and high stability to a wide range of
      temperatures and pH values. Restriction analyses demonstrated that phage consists
      of a double-stranded DNA with an approximate genome size of 40 Kb. BLAST results
      did not show high similarity (megablast) with other previously identified phages.
      But, in Blastn, similarity with Staphylococcus phages was observed. Phage
      vB_SsapS-104 represented high anti-bacterial activity against S. saprophyticus
      isolates in vitro as it was able to lyse 8 of the 9 clinical isolates (%88.8)
      obtained from a hospital in Gorgan, Iran. It was a S. saprophyticus-specific
      phage because no lytic activity was observed on some other pathogenic bacteria
      tested. Therefore, phage vB_SsapS-104 can be considered as a specific virulent
      phage against of S. saprophyitcus isolated from urinary tract infection. This
      study provided the partial genomic characterization of S. saprophyticus phage and
      its application against urinary tract infection associated with S. saprophyticus.
      This phage also can be considered as a good candidate for a therapeutic
      alternative in the future.

PMID- 30284665
TI  - Using Patient-Derived Induced Pluripotent Stem Cells to Identify Parkinson's
      Disease-Relevant Phenotypes.
AB  - PURPOSE OF REVIEW: Parkinson's disease (PD) is the second most common
      neurodegenerative disorder affecting older individuals. The specific cause
      underlying dopaminergic (DA) neuron loss in the substantia nigra, a pathological
      hallmark of PD, remains elusive. Here, we highlight peer-reviewed reports using
      induced pluripotent stem cells (iPSCs) to model PD in vitro and discuss the
      potential disease-relevant phenotypes that may lead to a better understanding of
      PD etiology. Benefits of iPSCs are that they retain the genetic background of the
      donor individual and can be differentiated into specialized neurons to facilitate
      disease modeling. RECENT FINDINGS: Mitochondrial dysfunction, oxidative stress,
      ER stress, and alpha-synuclein accumulation are common phenotypes observed in PD
      iPSC-derived neurons. New culturing technologies, such as directed reprogramming
      and midbrain organoids, offer innovative ways of investigating intraneuronal
      mechanisms of PD pathology. PD patient-derived iPSCs are an evolving resource to
      understand PD pathology and identify therapeutic targets.

PMID- 30284671
TI  - Standardization of Autoantibody Testing in Autoimmune Hepatitis.
AB  - It is a comment on a recent review published on the Journal.

PMID- 30284672
TI  - Fused Group Lasso Regularized Multi-Task Feature Learning and Its Application to
      the Cognitive Performance Prediction of Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is characterized by gradual neurodegeneration and loss
      of brain function, especially for memory during early stages. Regression analysis
      has been widely applied to AD research to relate clinical and biomarker data such
      as predicting cognitive outcomes from MRI measures. Recently, multi-task based
      feature learning (MTFL) methods with sparsity-inducing [Formula: see text]-norm
      have been widely studied to select a discriminative feature subset from MRI
      features by incorporating inherent correlations among multiple clinical cognitive
      measures. However, existing MTFL assumes the correlation among all tasks is
      uniform, and the task relatedness is modeled by encouraging a common subset of
      features via sparsity-inducing regularizations that neglect the inherent
      structure of tasks and MRI features. To address this issue, we proposed a fused
      group lasso regularization to model the underlying structures, involving 1) a
      graph structure within tasks and 2) a group structure among the image features.
      To this end, we present a multi-task feature learning framework with a mixed norm
      of fused group lasso and [Formula: see text]-norm to model these more flexible
      structures. For optimization, we employed the alternating direction method of
      multipliers (ADMM) to efficiently solve the proposed non-smooth formulation. We
      evaluated the performance of the proposed method using the Alzheimer's Disease
      Neuroimaging Initiative (ADNI) datasets. The experimental results demonstrate
      that incorporating the two prior structures with fused group lasso norm into the
      multi-task feature learning can improve prediction performance over several
      competing methods, with estimated correlations of cognitive functions and
      identification of cognition-relevant imaging markers that are clinically and
      biologically meaningful.

PMID- 30284670
TI  - Acceptability of two- versus three-dose human papillomavirus vaccination schedule
      among providers and mothers of adolescent girls: a mixed-methods study in five
      countries.
AB  - PURPOSE: The World Health Organization revised its human papillomavirus (HPV)
      vaccination recommendations to include a two (2-) dose schedule for girls aged <=
      15 years. We investigated acceptability of 2- versus 3-dose schedule among
      adolescent vaccination providers and mothers of adolescent girls in five
      countries. METHODS: Adolescent vaccination providers (N = 151) and mothers of
      adolescent girls aged 9-14 years (N = 118) were recruited from Argentina,
      Malaysia, South Africa, South Korea, and Spain. We assessed providers' preference
      for a 2- versus 3-dose HPV vaccination schedule via quantitative surveys.
      Mothers' attitudes towards a 2-dose schedule were assessed through focus group
      discussions. RESULTS: Most adolescent providers preferred a 2- over a 3-dose HPV
      vaccination schedule (overall: 74%), with preference ranging from 45.2% (South
      Africa) to 90.0% (South Korea). Lower cost, fewer clinic visits, and higher
      series completion were commonly cited reasons for 2-dose preference among
      providers and mothers. Safety and efficacy concerns were commonly cited barriers
      to accepting a 2-dose HPV vaccination schedule among providers and mothers.
      Mothers generally accepted the reduced schedule, however requested further
      information from a trusted source. CONCLUSIONS: Adolescent vaccination providers
      and mothers preferred the 2-dose over 3-dose HPV vaccination schedule.
      Acceptability of a 2-dose HPV vaccination could be improved with additional
      information to providers and mothers on HPV vaccination safety and efficacy.

PMID- 30284673
TI  - The 1980s: D-AP5, LTP and a Decade of NMDA Receptor Discoveries.
AB  - In the 1960s and 70s, biochemical and pharmacological evidence was pointing
      toward glutamate as a synaptic transmitter at a number of distinct receptor
      classes, known as NMDA and non-NMDA receptors. The field, however, lacked a
      potent and highly selective antagonist to block these putative postsynaptic
      receptors. So, the discoveries in the early 1980s of D-AP5 as a selective NMDA
      receptor antagonist and of its ability to block synaptic events and plasticity
      were a major breakthrough leading to an explosion of knowledge about this
      receptor subtype. During the next 10 years, the role of NMDA receptors was
      established in synaptic transmission, long-term potentiation, learning and
      memory, epilepsy, pain, among others. Hints at pharmacological heterogeneity
      among NMDA receptors were followed by the cloning of separate subunits. The
      purpose of this review is to recognize the important contributions made in the
      1980s by Graham L. Collingridge and other key scientists to the advances in our
      understanding of the functions of NMDA receptors throughout the central nervous
      system.

PMID- 30284674
TI  - A Novel Ileocolonic Release Peppermint Oil Capsule for Treatment of Irritable
      Bowel Syndrome: A Phase I Study in Healthy Volunteers.
AB  - INTRODUCTION: Peppermint oil (PO) has been shown to reduce abdominal pain in
      patients with irritable bowel syndrome (IBS). PO is assumed to induce intestinal
      smooth muscle relaxation and desensitization of nociceptive nerve afferents. To
      increase colonic PO concentration, an ileocolonic release peppermint oil (IC-PO)
      capsule has been developed. The aim of this study was to compare pharmacokinetic
      parameters of the currently available small intestinal release PO (SI-PO) and the
      novel IC-PO. METHODS: In this randomized, double-blind, crossover study, subjects
      received 182 mg of either SI-PO or IC-PO in a crossover design with a washout
      period of more than 14 days. Blood samples were collected to determine menthol
      glucuronide concentrations. RESULTS: Eight healthy volunteers (50% female, median
      age 22) were included. The time to reach the maximum concentration (Tmax) of IC
      PO was significantly longer compared to SI-PO with a median (IQR) of 360 (360
      405) versus 180 (120-180) min. The lag time (Tlag) was significantly longer with
      a median (IQR) of 225 (204-284) for IC-PO compared to 37 (6-65) min for SI-PO.
      The areas under the menthol glucuronide plasma concentration-time curves were
      significantly smaller with a median (IQR) of 2331 MUg h/L (2006-2510) for IC-PO
      compared to 2623 MUg h/L (2471-2920) for SI-PO. No significant differences were
      found in peak concentrations and elimination half-lives. CONCLUSION: IC-PO has a
      significantly delayed peak menthol glucuronide concentration and Tlag, both
      pointing to the release of PO in the more distal part of the intestine. This may
      enhance therapeutic efficacy as it results in increased exposure of colonic
      mucosal afferents to the PO. A randomized controlled trial investigating the
      efficacy of SI and IC-PO in IBS is currently ongoing. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier, NCT02291445, EudraCT database 2014-004195-32.

PMID- 30284675
TI  - Ethanol via Regulation of NF-kappaB/p53 Signaling Pathway Increases Manganese
      Induced Inflammation and Apoptosis in Hypothalamus of Rats.
AB  - The diet is a major route of manganese (Mn) exposure for humans. Interestingly,
      several epidemiological data demonstrated an increase in the incidence of alcohol
      consumption globally. Chemical-chemical interaction subsequent to chemical
      mixtures exposure may result in a synergism or antagonism effects. The present
      study investigated the influence of co-exposure to ethanol (EtOH) and Mn on
      inflammation and apoptosis in the hypothalamus of rats. The study consisted of
      five groups of rats that were exposed to drinking water alone, EtOH alone at 5
      g/kg, Mn alone at 30 mg/kg or co-expose with EtOH at 1.25 and 5 g/kg body weight
      by oral gavage for 35 consecutive days. The results indicated that the
      significant (p < 0.05) increases in pro-inflammatory cytokines, namely tumor
      necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1beta) as well as
      cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-kappaB) activation in the
      hypothalamus following individual exposure to Mn and EtOH to rats were
      intensified in the co-exposure group. Moreover, immunohistochemistry analysis
      showed marked decrease in B cell lymphoma-2 (Bcl-2) protein expression as well as
      the increases in the apoptotic proteins, namely Bax and caspase-3 along with p53
      in the hypothalamus of rats treated with Mn or EtOH alone were intensified in the
      co-exposure group. Taken together, these findings highlight that EtOH exacerbated
      the induction of inflammatory and apoptotic biomarkers via regulation of NF
      kappaB/p53 signaling pathways in the hypothalamus of rats. These alterations may
      have profound disrupting effects on the hypothalamus functions such as impairment
      of it metabolic and autonomic nervous system functions.

PMID- 30284676
TI  - Excessive corticosterone induces excitotoxicity of hippocampal neurons and
      sensitivity of potassium channels via insulin-signaling pathway.
AB  - Corticosterone (CORT) is a kind of corticosteroid produced by cortex of adrenal
      glands. Hypothalamic-pituitary-adrenal (HPA) axis hyperfunction leads to
      excessive CORT, which is associated with depression. Few studies have
      investigated the role of CORT in voltage-gated ion channels and its upstream
      signaling pathway in central nervous system. In this study, we investigated the
      mechanism of excessive CORT resulting in brain impairment on voltage-gated ion
      channels, and its upstream signaling effectors in hippocampal CA1 neurons. The
      action potential (AP) and voltage-gated potassium currents were determined by
      using whole-cell patch-clamp. Insulin and CORT improved the neuronal
      excitability. Independent effects existed in transient potassium channel (IA) and
      delay rectifier potassium channel (IK). The inhibition of potassium currents, IA
      in our experiment, could increase neuronal excitability. CORT led to the
      excitotoxicity of hippocampal neurons via phosphatidylinositol 3 kinase (PI3K)
      mediated insulin-signaling pathway. Therefore, the stimulation of excessive CORT
      induces excitotoxicity of hippocampal neurons and sensitivity of potassium
      channels via PI3K-mediated insulin-signaling pathway, which indicates one
      possible way of depression treatment.

PMID- 30284677
TI  - Alkaline phosphatase: a potential biomarker for stroke and implications for
      treatment.
AB  - Stroke is the fifth leading cause of death in the U.S., with more than 100,000
      deaths annually. There are a multitude of risks associated with stroke, including
      aging, cardiovascular disease, hypertension, Alzheimer's disease (AD), and immune
      suppression. One of the many challenges, which has so far proven to be
      unsuccessful, is the identification of a cost-effective diagnostic or prognostic
      biomarker for stroke. Alkaline phosphatase (AP), an enzyme first discovered in
      the 1920s, has been evaluated as a potential biomarker in many disorders,
      including many of the co-morbidities associated with stroke. This review will
      examine the basic biology of AP, and its most common isoenzyme, tissue
      nonspecific alkaline phosphatase (TNAP), with a specific focus on the central
      nervous system. It examines the preclinical and clinical evidence which supports
      a potential role for AP in stroke and suggests potential mechanism(s) of action
      for AP isoenzymes in stroke. Lastly, the review speculates on the clinical
      utility of AP isoenzymes as potential blood biomarkers for stroke or as AP
      targeted treatments for stroke patients.

PMID- 30284678
TI  - Purkinje Neurons: Development, Morphology, and Function.
AB  - Cerebellar Purkinje neurons are arguably some of the most conspicuous neurons in
      the vertebrate central nervous system. They have characteristic planar fan-shaped
      dendrites which branch extensively and fill spaces almost completely with little
      overlap. This dendritic morphology is well suited to receiving a single or a few
      excitatory synaptic inputs from each of more than 100,000 parallel fibers which
      run orthogonally to Purkinje cell dendritic trees. In contrast, another type of
      excitatory input to a Purkinje neuron is provided by a single climbing fiber,
      which forms some hundreds to thousands of synapses with a Purkinje neuron. This
      striking contrast between the two types of synaptic inputs to a Purkinje neuron
      has attracted many neuroscientists. It is also to be noted that Purkinje neurons
      are the sole neurons sending outputs from the cerebellar cortex. In other words,
      all computational results within the cortex are transmitted by Purkinje cell
      axons, which inhibit neurons in the cerebellar or vestibular nucleus. Notably,
      Purkinje neurons show several forms of synaptic plasticity. Among them, long-term
      depression (LTD) at parallel fiber synapses has been regarded as a putatively
      essential mechanism for cerebellum-dependent learning. In this special issue on
      Purkinje neurons, you will find informative reviews and original papers on the
      development, characteristics and functions of Purkinje neurons, or related themes
      contributed by outstanding researchers.

PMID- 30284679
TI  - Vertebral fracture resulting from cardioversion for atrial fibrillation.

PMID- 30284680
TI  - Homozygous 2p11.2 deletion supports the implication of ELMOD3 in hearing loss and
      reveals the potential association of CAPG with ASD/ID etiology.
AB  - Autism spectrum disorder (ASD) is a set of neurodevelopmental conditions
      characterized by early-onset difficulties in social communication and unusually
      restricted, repetitive behavior and interests. Parental consanguinity may lead to
      higher risk of ASD and to more severe clinical presentations in the offspring.
      Studies of ASD families with high inbreeding enable the identification of
      inherited variants of this disorder particularly those with an autosomal
      recessive pattern of inheritance. In our study, using copy number variants (CNV)
      analysis, we identified a rare homozygous deletion in 2p11.2 region that affects
      ELMOD3, CAPG, and SH2D6 genes in a boy with ASD, intellectual disability (ID),
      and hearing impairment (HI). This deletion may reveal a new contiguous deletion
      syndrome in which ELMOD3, known to be implicated in autosomal recessive deafness
      underlies the HI of the proband and CAPG, member of actin regulatory proteins
      involved in cytoskeletal dynamic, an important function for brain development and
      activity, underlies the ASD/ID phenotype. A possible contribution of SH2D6 gene,
      as a part of a chimeric gene, to the clinical presentation of the patient is
      discussed. Our result supports the implication of ELMOD3 in hearing loss and
      highlights the potential clinical relevance of 2p11.2 deletion in autism and/or
      intellectual disability.

PMID- 30284681
TI  - Structural and copy number chromosome abnormalities in canine cutaneous mast cell
      tumours.
AB  - Mast cell tumours (MCTs) are the most common skin tumours in dogs. Their clinical
      behaviour is variable and their aetiology remains largely unknown. We performed a
      metaphase fluorescence in situ hybridisation (FISH) with whole chromosome
      painting probes, and interphase FISH with BAC probes for 14 cancer-related genes
      to reveal clonal structural chromosome rearrangements and copy number variants
      (CNVs) in canine cutaneous MCTs. The metaphase FISH performed in three MCTs
      revealed several clonal monosomies and trisomies and two different chromosome
      rearrangements. No centric fusions were detected. The interphase FISH showed a
      variety of low frequency CNVs for the individual cancer-related genes. The
      heterogeneous character of the detected abnormalities indicates increased
      chromosome instability in canine MCTs. The clonal gain of chromosome 11 was
      detected in 81% (13/16) of the MCTs. Further research is needed to evaluate the
      significance of this abnormality as prognostic factor for the survival time or
      recurrence risk assessments in canine cutaneous MCTs.

PMID- 30284682
TI  - Ruthenium pyridyl thiocyanate complex increased the production of pro
      inflammatory TNFalpha and IL1beta cytokines by the LPS stimulated mammalian
      macrophages in vitro.
AB  - Every cell in our body depends on the electron transport processes in order to
      generate energy and function properly. Being able to regulate the metabolic
      activity of a cell would enable us altering its function and eventually lead us
      to a desired biological outcome at the cellular level and more desirably at a
      systemic level. Immunomodulatory or immunostimulatory molecules have been focus
      of the recent studies in order to regulate or boost the activities of the immune
      system cells and suppress or eliminate the disease conditions such as cancer,
      autoimmune reactions, inflammatory disorders as well as infections. In our study
      we used a ruthenium pyridyl thiocyanate complex, K330, to examine its effect on
      the activity of the innate immune system cells, macrophages in vitro. K330 was
      our candidate due to its application in the solar cells. Especially, due to its
      ability to get involved in electron transfer systems we hypothesized that it
      could change the activity of the immune system cells at cellular level, possibly
      by interfering the electron transfer reactions of the cells. Our results support
      our hypothesis since K330 lead to a significant increase in TNFalpha and IL1beta
      cytokine production levels by LPS stimulated macrophages compared to only LPS
      treated control groups. Based on our in vitro results, K330 can also be utilized
      as an adjuvant candidate in vaccinations where the antigen itself is not
      sufficient to generate a proper immune response.

PMID- 30284683
TI  - Building Capacity for Productive Indigenous Community-University Partnerships.
AB  - This paper describes capacity development as a key aspect of community-based
      research with indigenous communities. University research engagement with
      indigenous communities includes extensive, and often negative, historical
      antecedents. We discuss strategies for developing effective, egalitarian, and
      balanced indigenous community-university relationships to build research capacity
      of these communities, and to create sustainable partnerships to improve health
      and wellness, and to reduce health disparities. We draw on the experience of
      eight investigators conducting research with indigenous communities to assess
      effective strategies for building and enhancing partnerships, including (1)
      supporting indigenous investigator development; (2) developing university
      policies and practices sensitive and responsive to Indigenous community settings
      and resources, and training for research; (3) developing community and
      scientifically acceptable research designs and practices; (4) aligning indigenous
      community and university review boards to enhance community as well as individual
      protection (e.g., new human subjects training for Indigenous research, joint
      research oversight, adaptation of shorter consent forms, appropriate incentives,
      etc.); (5) determining appropriate forms of dissemination (i.e., Indian Health
      Services provider presentation, community reports, digital stories, etc.); (6)
      best practices for sharing credit; and (7) reducing systematic discrimination in
      promotion and tenure of indigenous investigators and allies working in indigenous
      communities.

PMID- 30284684
TI  - Small intestinal bacterial overgrowth in cirrhosis: systematic review and meta
      analysis.
AB  - BACKGROUND: Small intestinal bacterial overgrowth (SIBO) was detected in
      cirrhosis in many studies. The aim is to perform a systematic review and meta
      analysis on the prevalence of SIBO in cirrhosis and on the relationship of SIBO
      with features of cirrhosis. METHODS: PUBMED search (until 14 January 2018) was
      performed. Specific search terms were: '(cirrhosis) AND (SIBO OR bacterial
      overgrowth)'. Studies not relating to cirrhosis or SIBO, animal studies, and non
      original articles were excluded. A meta-analysis of all studies was performed
      using a random-effects model. RESULTS: 117 references were identified by the
      PUBMED search. 3 references were added after handsearching the reference lists of
      all the articles. 99 references were excluded. 21 studies (included in total 1264
      cirrhotics and 306 controls) remained for qualitative analysis and quantitative
      synthesis. Prevalence of SIBO for cirrhosis was 40.8% (95% CI 34.8-47.1), while
      the prevalence of SIBO for controls was 10.7% (95% CI 5.7-19.0). OR 6.83 (95% CI
      4.16-11.21; p < 0.001). Prevalence of SIBO for decompensated cirrhosis was higher
      than prevalence of SIBO for compensated cirrhosis (50.5% vs. 31.2%; p < 0.001).
      SIBO in cirrhosis was associated with ascites (p < 0.001), minimal hepatic
      encephalopathy (p = 0.001), bacterial translocation (p = 0.026), spontaneous
      bacterial peritonitis (p = 0.008), prolonged orocecal transit time (p < 0.001),
      and was not associated with hypocoagulation. Further studies are required to
      clarify the relationship of SIBO with hyperbilirubinemia, hypoalbuminemia, overt
      hepatic encephalopathy in past, esophageal varices and systemic inflammation.
      CONCLUSION: Small intestinal bacterial overgrowth is more often detected in
      cirrhosis than in healthy persons and is associated with some features of
      cirrhosis.

PMID- 30284685
TI  - A phase II study of lenalidomide consolidation and maintenance therapy after
      autologous PBSCT in patients with multiple myeloma.
AB  - The efficacy and safety of lenalidomide (LEN) consolidation therapy and
      subsequent LEN maintenance therapy after high-dose therapy with autologous
      peripheral blood stem cell transplantation (auto-PBSCT) were evaluated in
      patients with newly diagnosed symptomatic multiple myeloma (MM). Forty-one
      patients were enrolled and received high-dose dexamethasone (DEX) therapy as an
      initial induction. The patients who did not respond to the DEX therapy were
      further treated with four cycles of bortezomib plus DEX (BD) induction therapy.
      For patients who responded to BD, PBSC harvesting was scheduled following high
      dose cyclophosphamide and filgrastim administration. After PBSC harvesting, high
      dose chemotherapy of melphalan with auto-PBSCT was performed. One hundred days
      after auto-PBSCT, patients received consolidation therapy consisting two cycles
      of LEN plus low-dose DEX (Ld) and LEN maintenance therapy. Only one death
      occurred during mobilization therapy, but the protocol developed in this study
      was considered generally safe to provide. Overall response rates after
      consolidation and maintenance therapies were 73.7% and 81.6%, respectively. Two
      year progression-free survival and overall survival were 76.3% and 92.1%,
      respectively. These observations suggest that LEN consolidation and maintenance
      therapy are effective and safe, and provide favorable response rates in patients
      with MM.

PMID- 30284686
TI  - Mind the gap: closure of right to left shunts for rare indications.

PMID- 30284687
TI  - Non-invasive monitoring using photoplethysmography technology.
AB  - We evaluated the accuracy and precision of a novel non-invasive monitoring device
      in comparison with conventional monitoring methods used in intensive care units
      (ICU). The study device was developed to measure blood pressure, pulse rate,
      respiratory rate, and oxygen saturation, continuously with a single sensor using
      the photoplethysmographic technique. Patients who were monitored with arterial
      pressure lines in the ICU were enrolled. Systolic and diastolic blood pressure,
      pulse rate, respiratory rate, and arterial oxygen saturation were measured
      continuously for 30 min at 5-min intervals using the conventional methods and the
      study device. The primary outcome variable was blood pressure. Blood pressure
      measured by the study device highly correlated with the arterial pressure line
      values (correlation coefficients > 0.95). Percent errors for systolic, diastolic
      and mean blood pressures were 2.4% and 6.7% and 6.5%, respectively. Percent
      errors for pulse rate, respiratory rate and oxygen saturation were 3.4%, 5.6% and
      1.4%, respectively. The non-invasive, continuous, multi-parameter monitoring
      device presented high level of agreement with the invasive arterial blood
      pressure monitoring, along with sufficient accuracy and precision in the
      measurements of pulse rate, respiratory rate, and oxygen saturation.

PMID- 30284688
TI  - Retrospective Cohort Analysis of the Reduced Burden of Hypoglycemia Associated
      with Dipeptidyl Peptidase-4 Inhibitor Use in Patients with Type 2 Diabetes
      Mellitus.
AB  - INTRODUCTION: The use of antihyperglycemic agents (AHA), especially insulin and
      sulfonylureas (SU), is a risk factor for hypoglycemia. Despite the significant
      clinical and economic burdens associated with hypoglycemia and the decreasing use
      of SU in favor of other oral AHA, relatively little is known about hypoglycemia
      trends specific to the use of non-insulin AHA. We sought to estimate annual
      hypoglycemia event rates and costs among patients with type 2 diabetes mellitus
      (T2DM) who started either SU or dipeptidyl peptidase-4 inhibitors (DPP-4i) and to
      predict rates and costs in the absence of DPP-4i. METHODS: Truven's MarketScan
      Commercial Claims database was used to estimate hypoglycemia event rates and
      costs from 2007 to 2013. Hypoglycemia, defined using diagnosis codes, was
      assessed during the 12 months following SU (n = 245,201) or DPP-4i (n = 176,786)
      initiation by adults with T2DM. Coefficients from a Poisson regression model used
      to estimate the impact of patient characteristics on hypoglycemia rates for
      patients who started SU were used to predict rates for patients who started DPP
      4i had they started SU instead. RESULTS: Hypoglycemia events per 100 patient
      years (costs per event) ranged from 5.4 ($565) in 2007 to 10.4 ($1154) in 2013
      for patients starting SU; rates (costs) for patients starting DPP-4i ranged from
      3.2 ($308) in 2007 to 6.4 ($482) in 2013. Predicted hypoglycemia rates would have
      been 5.3-9.9 per 100 person-years for patients who started DPP-4i had they
      started SU instead. Starting DPP-4i, rather than SU, would have resulted in
      national savings of $750.3 million in healthcare costs due to avoided
      hypoglycemia events during this period. CONCLUSIONS: Hypoglycemia rates and costs
      were consistently higher for patients who started SU rather than DPP-4i. The
      overall burden of hypoglycemia could be lowered substantially in the USA if, when
      feasible, patients with T2DM initiate DPP-4i instead of SU. FUNDING: Merck & Co.,
      Inc., Kenilworth, NJ USA.

PMID- 30284689
TI  - Investigating the Reliability of HbA1c Monitoring for Blood Glucose Control
      During Late Pregnancy in Patients with Gestational Diabetes Mellitus (GDM) with
      and without beta-Thalassemia Minor.
AB  - INTRODUCTION: Patients with gestational diabetes mellitus (GDM) need strict blood
      glucose control to reduce the incidence of perinatal complications in the mother
      or infant. The purpose of this study was to investigate whether the glycated
      hemoglobin (HbA1c) values of GDM patients were affected by beta-thalassemia minor
      and to subsequently discuss the limitations of HbA1c monitoring for blood glucose
      control. METHODS: 41 GDM patients with beta-thalassemia minor were enrolled to
      serve as the study group. 93 GDM patients without thalassemia were randomly
      selected as a control group. Clinical data on the 134 mothers as well as their
      newborns were retrospectively analyzed. The blood glucose values of the
      participants at various times during the gestation period were compared between
      the groups, as were their HbA1c and ferritin levels and iron deficiency rates in
      late pregnancy (36-38 weeks of gestation). Pearson's coefficient was calculated
      to determine the correlations between HbA1c and ferritin in both the study and
      control groups. RESULTS: The study and control groups did not show any
      significant differences in newborn birth weight, maternal age, maternal pre
      pregnancy body mass index (BMI), gestational age, newborn sex, gravidity, and
      parity. The blood glucose values of the participants at different times during
      the gestation period also did not differ significantly between the study group
      and the control group. However, the late-pregnancy HbA1c level (5.23 +/- 0.49%)
      and iron deficiency rate (12.19%) in the study group were significantly lower
      than those in the control group (5.42 +/- 0.43% and 58.06%, respectively); P  <
      0.05. Also, the late-pregnancy ferritin level in the study group (46.59 +/- 18.03
      ng/mL) was significantly higher than that in the control group (25.58 +/- 11.42
      ng/mL); P  < 0.05. In addition, a significant negative correlation was observed
      between HbA1c and ferritin in both the study group (R = - 0.459, P = 0.003) and
      the control group (R = - 0.358, P = 0.010). CONCLUSIONS: The HbA1c level is
      affected by many factors. Using serum HbA1c values to monitor blood glucose in
      GDM patients with beta-thalassemia minor may lead to a mistaken assumption of low
      blood glucose levels, so HbA1c may not be a suitable indicator for monitoring
      blood glucose in pregnant women, particularly GDM patients with beta-thalassemia
      minor.

PMID- 30284690
TI  - A clinical compilation of lymph node pathologies comparing the diagnostic
      performance of biopsy methods.
AB  - PURPOSE: It is critical to obtain sufficient tissue, both in quality and
      quantity, in biopsy applications for histopathological review. Our aim was to
      compare fine-needle aspiration cytology (FNAC) and core needle biopsy (CNB)
      techniques in terms of their diagnostic performance in lymph node biopsies. This
      was a clinical compilation, and histopathological results from biopsies were also
      evaluated. METHODS: A total of 242 patients and 246 lymph nodes were
      prospectively evaluated. All histopathologic specimens were obtained through
      ultrasonography-guided biopsies performed at our institute between April 2015 and
      October 2017. Histopathological results were grouped according to diagnostic
      performance, and the mean performance scores of the two methods were compared.
      RESULTS: For FNAC, the mean diagnostic score was calculated to be 1.63, whereas
      for CNB, the mean diagnostic score was calculated to be 1.89. The difference
      between diagnostic scores of the two techniques was statistically significant (p
      < 0.01). CONCLUSION: We recommend that interventional radiologists perform vacuum
      assisted biopsies if there are no financial hindrances or evidence of
      psychological issues in patients. We recommend this not only for lymph nodes of
      malignant appearance but also for those that appear benign.

PMID- 30284691
TI  - Adaptation to Occupational Exposure to Moderate Endotoxin Concentrations: A Study
      in Sewage Treatment Plants in Germany.
AB  - Acute or chronic inhalation of endotoxin may lead to changes of lung function and
      inflammatory markers in the airways. Adaptation to workplace exposure may be
      possible. In this study, we investigated the possible difference in inflammatory
      markers assessed in nasal lavage fluid (NALF) in chronical exposure compared to
      voluntary subjects exposed acutely to endotoxin. We sought to define the
      variability of inflammatory markers in NALF and the dose-related changes after
      moderate exposure in naive subjects. Endotoxin exposure (4-1039 EU/m3) resulted
      from routine work during one shift in sewage treatment plants. Subjects were
      matched to pairs (8 workers escorted by 10 students). Inflammatory markers were
      investigated before, directly after, and 16 h after the shift end. Additional
      NALF samples were collected in students without any specific exposure after 3
      days. In NALF, total cell count, and interleukin (IL)-8 and IL-1beta
      concentrations were significantly higher in workers than in students at all times
      pointing to workplace-related long-lasting exposure resulting in adaptation.
      However, concentration of inflammatory markers without specific exposure in
      students showed a great variability, covering the whole range of values recorded
      in the workers. The findings of this study make us to recommend a repeated
      assessment of inflammatory markers in healthy volunteers before the investigation
      of exposure-related changes and a sample size adequate for statistical analysis.

PMID- 30284692
TI  - Osteoprotegerin, Receptor Activator of Nuclear Factor Kappa B Ligand, and Growth
      Hormone/Insulin-Like Growth Factor-1 Axis in Children with Growth Hormone
      Deficiency.
AB  - The growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis is involved in
      the regulation of the receptor activator of nuclear factor kappa B ligand
      (RANKL)/RANK/osteoprotegerin (OPG) system, but the exact mechanism of the
      associations is not fully explained. In this study we investigated the serum OPG
      and total sRANKL concentrations in short children who had differences in GH
      secretory status. We also investigated the associations between the GH/IGF-1 and
      OPG/RANKL systems in GH-deficient children during GH treatment. There were no
      significant differences in any anthropometric or biochemical parameters evaluated
      between the GH-deficient and GH-sufficient children. The OPG content and total
      alkaline phosphatase (ALP) activity increased significantly after the initiation
      of GH treatment, while total sRANKL remained unchanged. The variables baseline
      BMI SDS for height-age (beta = 0.42; p < 0.05), baseline ALP activity (beta =
      0.36; p < 0.05), weight SDS for height-age at 6 months of GH treatment (beta =
      1.86; p < 0.01), and total ALP activity at 6 months of GH treatment (beta = 0.48,
      p < 0.01) were identified as independent predictors of DeltaOPG6-month-baseline.
      We conclude that OPG and total sRANKL concentrations are independent from GH
      secretory status in short children. OPG elevation during GH treatment is
      independently associated with total ALP activity and nutritional status in GH
      deficient children.

PMID- 30284693
TI  - Time for a Different Approach to Anterior Cruciate Ligament Injuries: Educate and
      Create Realistic Expectations.
AB  - Following an anterior cruciate ligament (ACL) injury, patients are often
      reassured that timely surgery followed by intensive physiotherapy will "fix their
      knee". Not only does this message create a false perception of uncomplicated
      return to sport (RTS), it also ignores the large body of evidence demonstrating a
      high RTS re-injury rate following ACL reconstruction. In this article, we propose
      an individualised approach to the management of ACL injuries that targets a shift
      away from early surgery and towards conservative management, with surgery 'as
      needed' and rehabilitation tailored to the patient's RTS goals. Education on the
      natural history of ACL injuries will ensure patients are not misguided into
      thinking surgery and intensive rehabilitation guarantees great outcomes. Further,
      understanding that conservative management is not inferior to surgery-and not
      more likely to cause knee osteoarthritis-will help the patient make an informed
      decision. For patients who opt for surgical management, rehabilitation must
      target strength and functional performance, avoid rapid increases in training
      load, and be guided by an RTS timeframe that is no shorter than 9 months. The
      content of rehabilitation should be similar for patients who opt for non
      operative management, although the RTS timeframe will likely be shorter. All
      patients should receive education on the relationship between injury risk and
      training load, and understand that a home-exercise program is not inferior to
      intensive physiotherapist-led exercise.

PMID- 30284694
TI  - Molecular topology and QSAR multi-target analysis to boost the in silico research
      for fungicides in agricultural chemistry.
AB  - The aim of the present study is to show how molecular topology can be a powerful
      in silico tool for the prediction of the fungicidal activity of several
      diphenylamine derivatives against three fungal species (cucumber downy mildew,
      rice blast and cucumber gray mold). A multi-target QSAR model was developed, and
      two strategies were followed. First is the construction of a virtual library of
      molecules using DesMol2 program and a subsequent selection of potential active
      ones. Second is the selection of molecules from the literature on the basis of
      molecular scaffolds. More than 700 diphenylamine derivatives designed and other
      60 fluazinam's derivatives with structural similarity higher than 80% were
      studied. Almost twenty percent of the molecules analyzed show potential activity
      against the three fungal species.

PMID- 30284695
TI  - Integrated Pulmonary Index (IPI) monitorization under sedation in cataract
      surgery with phacoemulsification technique.
AB  - PURPOSE: We aimed to investigate that change of IPI values after sedation of
      patients undergoing cataract surgery under sedation. METHODS: We included 50
      patients (ASA I-III) undergoing cataract surgery under sedation by
      phacoemulsification method in this prospective observational study. IPI, SpO2,
      ETCO2, respiratory rate (RR), peripheral pulse rate (PR), hemodynamic data and
      BIS values and perioperative complications were recorded. RESULTS: Compared to
      baseline values, RR value at 5th min, RR, PR, IPI values at 10th min and RR, PR
      values at 15th min were significantly low and heart rate value at 15th min and
      arterial pressure, bispectral index (BIS) values at 5th min, 10th min, 15th min,
      20th min, 25th min and 30th min were lower than baseline values. CONCLUSIONS: IPI
      monitoring will provide guidance during sedation of patients with comorbid
      diseases undergoing cataract surgery by phacoemulsification method.

PMID- 30284696
TI  - Exploration of factors determining milk production by Holstein cows raised on a
      dairy farm in a temperate climate area.
AB  - In this study, we examined factors that affected milk production by cows raised
      in a temperate climate area. We conducted this study on a large dairy farm
      containing approximately 2000 Holstein cows, located in a temperate climate area.
      We collected 7803 calving records for 4069 cows from 2012 to 2016. We then
      assessed the effect of hot weather on milk yield by examining three climate
      factors: season, maximum temperature (MAX), and the temperature and humidity
      index (THI). We found that increases in heat stress caused linear decreases in
      milk yield (P < 0.05). Additionally, the effects of the three climate factors on
      milk yield varied depending on cow parity and days open (P < 0.05). Thus,
      management procedures should consider cow parity and lactating stage to minimize
      the negative effects of heat stress on milk production. We also found that the
      lowest Akaike information criterion value was obtained in our model when using
      THI for 305-day milk yield. This suggests that THI is a more accurate variable
      for evaluating heat stress than MAX or season.

PMID- 30284697
TI  - Major ion and dissolved heavy metal geochemistry, distribution, and relationship
      in the overlying water of Dongting Lake, China.
AB  - Deteriorating lake water quality has become a serious environmental issue around
      the globe. Heavy metals dissolved in the overlying water of lakes are notably
      more toxic than those found in lake sediment. Given this, we sought to better
      understand the characteristics of particular major ion and dissolved heavy metal
      in Dongting Lake-the second largest freshwater lake in China. Overlying water
      samples were collected from Dongting Lake to investigate the major ion
      geochemistry and to examine the relationship between the major ions and dissolved
      heavy metals. Chemical analysis of the overlying water showed that the average
      cation concentration was the highest for Ca2+, followed by Mg2+, Na+, and K+.
      Similarly, the highest anion concentration was SO42-, followed by Cl-, NO3-, and
      HCO3-. Total dissolved solids in the overlying water of Dongting Lake ranged from
      66.19 to 159.20 mg/L, with an average value of 93.13 mg/L. The predominant
      hydrochemical type was Ca-SO4. The mean concentrations of dissolved heavy metal
      in both surface and deep waters decreased in the following order: Zn > Cr > Ni >
      Cu > Pb > Cd. Importantly, all of the selected heavy metals tested in the
      overlying water were lower than the corresponding toxicity reference values. Co
      occurrence network analyses were performed and compared the correlations between
      all measured major ions and heavy metals. Results of the subsequent principal
      component analyses revealed that heavy metal levels in the aquatic environment
      primarily originated from natural processes and were enhanced by anthropogenic
      activities.

PMID- 30284698
TI  - Correction to: Delafloxacin: First Global Approval.
AB  - The article Delafloxacin: First Global Approval, written by Anthony Markham, was
      originally published Online First without open access.

PMID- 30284699
TI  - Impaired Renal Function May Not Negate the Efficacy of Tolvaptan in the Treatment
      of Cirrhotic Patients with Refractory Ascites.
AB  - BACKGROUND AND OBJECTIVE: Tolvaptan, an oral vasopressin V2 receptor antagonist,
      has been widely used for the treatment of patients with cirrhosis and ascites.
      However, its efficacy in patients with renal dysfunction remains unknown. The
      objective of this study was to investigate the efficacy and safety of tolvaptan
      in patients with decompensated cirrhosis and severe chronic kidney disease (s
      CKD). METHODS: We studied 43 patients with liver cirrhosis who received tolvaptan
      (7.5 mg/day) for refractory ascites. s-CKD was defined as an estimated glomerular
      filtration rate (eGFR) < 45 mL/min/1.73 m2. Response to tolvaptan was defined as
      weight loss >= 1.5 kg in 7 days of treatment. RESULTS: Eighteen patients (42%)
      had s-CKD (s-CKD group), while the other 25 patients (58%) did not have s-CKD (n
      CKD group). Rates of response to tolvaptan were similar: 68% in the n-CKD group
      and 56% in the s-CKD group. Urine volumes increased significantly from baseline
      to day 7 in both groups. Incidences of adverse events were also similar (P =
      0.93). Mean eGFR did not decline even in the s-CKD group (27.3 +/- 2.2
      mL/min/1.73 m2 at baseline vs. 26.6 +/- 2.3 mL/min/1.73 m2 on day 7; P = 0.9).
      The cumulative survival rate did not differ significantly between the n-CKD and s
      CKD groups. In the s-CKD group, responders obtained a better prognosis than non
      responders. CONCLUSIONS: Tolvaptan significantly increased urine volumes
      similarly in patients with s-CKD and n-CKD without affecting renal function. As
      responders achieved a better prognosis, tolvaptan could be a good option to treat
      ascites in patients with cirrhosis and s-CKD.

PMID- 30284700
TI  - Safety and Plasma Concentrations of a Cyclin-dependent Kinase 9 (CDK9) Inhibitor,
      FIT039, Administered by a Single Adhesive Skin Patch Applied on Normal Skin and
      Cutaneous Warts.
AB  - BACKGROUND: Cutaneous warts are caused by human papilloma virus (HPV) infection.
      FIT039, a specific inhibitor of CDK9, suppresses the proliferation of DNA viruses
      in vitro. PURPOSE: We evaluated the safety, plasma concentrations, and efficacy
      of FIT039 delivered by single application of an adhesive skin patch on normal
      back skin and cutaneous warts. PATIENTS AND METHODS: In this placebo-controlled,
      dose-escalation, open-label, two-cohort phase I/II clinical trial, after a single
      administration of a 1% FIT039 patch, 3% FIT039 patch, or placebo on back skin,
      patients with cutaneous warts were treated with cryotherapy followed by a 1%
      FIT039 patch for 24 h in the first cohort. In the second cohort, cutaneous warts
      were treated with cryotherapy followed by a 3% FIT039 patch for 24 h. Adverse
      events and adverse drug reactions, the concentrations of FIT039, and surface area
      of cutaneous warts were evaluated. RESULTS: Neither irritant reactions nor
      symptoms related to FIT039 occurred when the FIT039 patches were applied to
      patients' backs or on warts in ten patients. The concentrations of FIT039 were
      under 0.1 ng/ml at every time point. The median wart surface area at 1 week after
      application of the 1% FIT039 patch was similar to baseline, while that of the 3%
      FIT039 patch was smaller than baseline. CONCLUSION: The FIT039 patch showed no
      topical or systemic adverse reactions when applied on normal skin or cutaneous
      warts. The safety and good adherence of the FIT039 patch are encouraging and
      support further studies to evaluate the efficacy of FIT039 in patients with
      cutaneous warts.

PMID- 30284701
TI  - Evaluating the Outcomes Associated with Genomic Sequencing: A Roadmap for Future
      Research.

PMID- 30284702
TI  - The use of mandibular advancement devices in obstructive sleep apnea: a proven
      and effective therapy.

PMID- 30284703
TI  - An extremely rare case who underwent total remnant pancreatectomy due to
      recurrent pancreatic metastasis of intraductal tubulopapillary neoplasm.
AB  - We describe a rare case of recurrent pancreatic metastasis of intraductal
      tubulopapillary neoplasm (ITPN). A 53-year-old woman diagnosed with an
      intraductal papillary mucinous neoplasm (IPMN) and a pancreatic ductal
      adenocarcinoma (PDAC) of the pancreatic body underwent a distal pancreatectomy.
      The tumor was composed of cuboidal, high-grade dysplastic cells proliferating in
      a tubulopapillary growth pattern without mucin production; hence, the final
      diagnosis was ITPN. A follow-up computed tomography scan revealed an enhanced 2
      cm mass of the pancreatic head 3 years after the surgery. From workup
      investigations, the patient was diagnosed with PDAC or a recurrent ITPN of the
      remnant pancreas. A total remnant pancreatectomy was then performed.
      Histopathological findings revealed that the new ITPN had the same features as
      the prior ITPN. In IPMNs, the presence of an invasive component and high-grade
      dysplasia can lead to progression to a recurring IPMN and the development of
      PDAC. Because there have been few reports of recurrent ITPN developing into PDAC,
      the risk factors for ITPN have not been investigated. Because of the uncertain
      clinicopathological characteristics of ITPN, more data should be gathered to
      assess the long-term outcome and malignant potential of ITPN.

PMID- 30284704
TI  - PF-06438179/GP1111: An Infliximab Biosimilar.
AB  - PF-06438179/GP1111 (Zessly(r); Ixifi(r)) [hereafter referred to as GP1111] is a
      biosimilar of the reference monoclonal anti-TNF-alpha antibody infliximab, and is
      approved in the EU and USA for the same indications as the reference drug,
      including rheumatoid arthritis (RA), Crohn's disease, ulcerative colitis
      (including paediatric ulcerative colitis in the EU), ankylosing spondylitis,
      psoriatic arthritis and plaque psoriasis; GP1111 is also approved in Japan.
      GP1111 has similar physicochemical characteristics and pharmacodynamic properties
      to those of reference infliximab, and the pharmacokinetic similarity of the
      agents has been shown in healthy volunteers and patients with moderate-to-severe
      RA despite methotrexate therapy. GP1111 demonstrated clinical efficacy equivalent
      to that of reference infliximab in patients with moderate-to-severe RA, despite
      methotrexate therapy, and was generally well tolerated in this population. The
      tolerability, immunogenicity and safety profiles of GP1111 were similar to those
      of reference infliximab, and switching from reference infliximab to GP1111 had no
      impact on safety, efficacy or immunogenicity. The role of reference infliximab in
      the management of autoimmune inflammatory conditions is well established and
      GP1111 provides an effective biosimilar alternative for patients requiring
      infliximab therapy.

PMID- 30284705
TI  - PET-MRI for the Study of Metabolic Bone Disease.
AB  - PURPOSE OF REVIEW: This review article attempts to summarize the current state
      and applications of the hybrid imaging modality of PET-MRI to metabolic bone
      diseases. The advances of PET and MRI are also discussed for metabolic bone
      diseases as potentially applied via PET-MRI. RECENT FINDINGS: Etiologies and
      mechanisms of metabolic bone disease can be complex where molecular changes
      precede structural changes. Although PET-MRI has yet to be applied directly to
      metabolic bone disease, possible applications exist since PET, specifically 18F
      NaF PET, can quantitatively track changes in bone metabolism and is useful for
      assessing treatment, while MRI can give detailed information on bone water
      concentration, porosity, and architecture through novel techniques such as UTE
      and ZTE MRI. Earlier detection and further understanding of metabolic bone
      disease via PET and MRI could lead to better treatment and prevention. More
      research using this modality is needed to further understand how it can be
      implemented in this realm.

PMID- 30284707
TI  - Correction to: Adsorption and removal of chromium (VI) contained in aqueous
      solutions using a chitosan-based hydrogel.
AB  - The original publication of this paper contains an error. The correct 4th heading
      in Table 1 should be "Non-linear sips isotherm". The original article has been
      corrected.

PMID- 30284706
TI  - EGFR Amplification and Sensitizing Mutations Correlate with Survival in Lung
      Adenocarcinoma Patients Treated with Erlotinib (MutP-CLICaP).
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) has a 5-year survival of 5-16%.
      Epidermal growth factor receptor (EGFR) mutations, in most cases, confer
      sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy. Nonetheless, it is
      still unclear why clinical outcomes vary among patients with identical EGFR
      mutations. The amplification of the EGFR gene (EGFRamp) may play a significant
      role. OBJECTIVE: Compare the complete (CR) and partial response (PR) rates,
      overall survival (OS), and progression-free survival (PFS) in Hispanic patients
      with lung adenocarcinoma treated with erlotinib with EGFR mutations (L858R or
      exon 19 deletion [Del19]) with and without concomitant EGFRamp. PATIENTS AND
      METHODS: Seventy-two EGFR-positive lung adenocarcinoma patients of Hispanic
      origin, who underwent first-line treatment with erlotinib, were evaluated for
      EGFRamp by fluorescence in situ hybridization (FISH). The clinical outcomes were
      analyzed according to EGFR mutations and EGFRamp status. RESULTS: 30.6% of
      samples showed EGFRamp, more frequently present in patients with Del19 (p =
      0.05). Patients with EGFRamp had a longer PFS (in months) [(28.5, 95% CI 22.3
      34.6) vs. (11.0, 95% CI 8.2-16.7); p = 0.002] and OS [(37.8, 95% CI 30.9-44.7)
      vs. (27.1, 95% CI 12.8-41.3); p = 0.009] than those without. EGFRamp
      significantly influenced the response to erlotinib (p = 0.0001). EGFRamp+/Del19
      had a longer OS, 37.8 (95% CI 31.0-44.6), compared to EGFRamp+/L8585R, 27.5 (95%
      CI 12.4-42.5) (p < 0.001) and longer PFS (p = 0.043). CONCLUSION: Among Hispanic
      patients, EGFRamp was present in 30% of patients with EGFR mutations. EGFR
      mutations and EGFRamp are associated with better OS, PFS, CR, and PR to erlotinib
      and, hence, could aid in the correct selection of patients that benefit from EGFR
      TKI treatment.

PMID- 30284708
TI  - Effect of biodiesel on PAH, OPAH, and NPAH emissions from a direct injection
      diesel engine.
AB  - Polycyclic aromatic hydrocarbon (PAH), oxy- and nitro-derivate PAH (OPAH and
      NPAH) emissions from a direct injection diesel engine fueled with conventional
      fossil diesel (D), waste cooking oil biodiesel (B100), and their two blends (B20
      and B50) were compared. The results show that B100 can reduce low molecular
      weight PAHs such as naphthalene, acenaphthylene, and fluorene as much as 90%
      compared with diesel. However, the emissions of high molecular weight PAHs
      including benzo[b]fluoranthene, benzo[k]fluoranthene, and benzo[a]pyrene decrease
      slightly when using B100. The emission levels for PAHs and OPAHs present
      comparable, while NPAH emission levels are five to ten times lower than those of
      PAHs and OPAHs. Compared with diesel, PAH and NPAH emissions significantly
      decrease. On the contrary, an increase trend of OPAH emission has been observed
      with adding biodiesel. For the specific parent PAHs and its oxygenated and
      nitrated derivatives, the fractions of parent PAHs gradually decrease with
      increasing biodiesel content in the blends, while the corresponding oxygenated
      and nitrated derivative fractions observably increase, especially for the high
      molecular weight compounds. Considering the increase of OPAH and NPAH fractions
      in total particle-phase PAHs when using biodiesel, in-depth biodiesel
      cytotoxicity assessment should be conducted.

PMID- 30284709
TI  - The content of the potentially toxic elements, iron and manganese, in the
      grapevine cv Tamjanika growing near the biggest copper mining/metallurgical
      complex on the Balkan peninsula: phytoremediation, biomonitoring, and some
      toxicological aspects.
AB  - Plants growing in areas polluted by heavy metals represent excellent models for
      the investigations related to their potentials for hazardous metals accumulation
      which further may help in the estimation of plant practical biomonitoring and
      phytoremediation potentials. In this study, the potentials of the grapevine
      cultivar Tamjanika from a highly polluted region in Eastern Serbia, with
      intensive copper mining and metallurgical activities, were estimated in regard to
      the potentially toxic elements such as iron and manganese; the potential danger
      from these metals through fruit consummation is also considered. Used methods
      were the following: ICP-OES analysis, calculation of biological coefficients, the
      Pearson correlation study, one-way ANOVA, and hierarchical cluster analysis. The
      results revealed that a great majority of the recorded concentrations in
      different plant organs were in the range of normal concentrations, as well as
      that the calculated accumulation rates for both metals were very low. The data
      also pointed to generally minimal to moderate enrichment by these metals which
      represents totally dissimilar situation in comparison with other heavy metals
      detected in the very same plant samples. The results of this study suggested that
      the investigated plants of the grapevine cv Tamjanika assimilated iron and
      manganese predominately according to their individual needs, and confirmed that
      the utilization of this plant species can be very effective in different
      biomonitoring procedures and also in the phytoremediation procedure known as
      phytostabilization. At the same time, it was obvious that even in aggressive
      circumstances its fruit was protected from some serious contamination and kept
      pretty safe for consummation.

PMID- 30284711
TI  - Early plant growth and bacterial community in rhizoplane of wheat and flax
      exposed to silver and titanium dioxide nanoparticles.
AB  - Silver and titanium dioxide nanoparticles (AgNPs and TiO2NPs) are highly useful,
      but they are also a significant reason for concern as they exert toxicity. The
      goal of research was to assess the role of three kinds of NPs in concentrations
      of 100 mg L-1 on early growth plants (wheat, flax) and bacterial community in
      rhizoplane. Titanium (IV) oxide anatase (TiO2NPs1) and titanium (IV) oxide
      nanopowder (TiO2NPs2) are commercial products. A suspension of AgNPs was prepared
      via a procedure of reduction with tannic acid. The response of Monocot and Dicot
      growth form plants to the tested NPs was different. Germination and seedling
      growth of wheat treated with TiO2NPs1 was better. The response of flax to NPs was
      noted as an increase of chlorophyll content. The bacterial community in wheat
      rhizoplane was not significantly modified, but there was a declining trend. In
      turn, a difference in the surface charge of NPs had an influence on the total
      bacterial community in Dicot rhizoplane. Positively charged TiO2NPs2
      significantly decreased the quantity of total bacteria in contrast to negatively
      charged AgNPs and TiO2NPs1 which increased it. A qualitative analysis did not
      confirm the influence of the surface charge of NPs on an increase/decrease in the
      quantity of Pseudomonas and Bacillus bacteria, but did show that there was no
      toxicity of the tested NPs to the plant growth-promoting bacteria community. The
      rhizoplane microbiome was dependent on the species of plant, and the bacteria
      found in the communities are sensitive to NPs to a varying degree.

PMID- 30284712
TI  - Summer fallow increases loss of residual nitrogen fertilizer in dryland of the
      Loess Plateau: a 15N-labeled method.
AB  - Summer fallow is very common in dryland agriculture to conserve rainwater and
      replenish soil fertility. However, bare land and intensive rainfall during summer
      fallow might result in a potential risk of N loss. We used a 15N-labelling method
      to study the loss of residual N fertilizer during summer fallow and its use by
      next wheat in the Loess Plateau. Our study included three treatments: without the
      addition of N (N0W0), with the addition of 50 kg ha-1 N (NW0) and with the
      addition of 50 kg ha-1 N plus 35% more water (NW). The N fertilizer (K15NO3) in
      solution was injected into the soil at a depth of 35 cm of the polyvinyl chloride
      (PVC) columns in field. The fates of 15N were followed after summer fallow and in
      the next season's wheat (Triticum aestivum L.). The summer fallow of this study
      was a dry summer; however, fertilizer 15N was still leached down to 40-cm depth
      for the NW0 treatment; and for the NW treatment, the peak of 15N fertilizer was
      approximately 20 cm deeper. After summer fallow, the loss of the initially
      applied 15N was 26% in the soil profile for the NW0 treatment; and for the NW
      treatment, it increased to 37%. Soil 15N abundance in 0-20 cm of the NW0 and NW
      treatments was higher than the N0W0 treatment, indicating the upward movement of
      15N in summer fallow. After the next wheat harvest, 15N uptake by wheat in the NW
      treatment decreased from 21.0 to 18.6% compared to the NW0 treatment. High
      rainfall during summer fallow increased residual N loss during summer fallow but
      decreased its use by the next crop.

PMID- 30284713
TI  - Effective reduction of metronidazole over the cryptomelane-type manganese oxide
      octahedral molecular sieve (K-OMS-2) catalyst: facile synthesis, experimental
      design and modeling, statistical analysis, and identification of by-products.
AB  - High concentrations of antibiotic compounds within pharmaceutical wastewater have
      hazardous impacts toward environment and human health. Therefore, there is an
      immediate requirement of efficient treatment method for removal of antibiotics
      from aquatic environment. In the present study, the cryptomelane catalyst-type
      manganese oxide octahedral molecular sieve (K-OMS-2) was synthesized in the
      presence of benzyl alcohol as a reducing agent and cetyltrimethylammonium bromide
      as a structure-directing agent and then utilized to reduce the metronidazole. The
      central composite design method was the experimental design adopted. The FESEM
      analysis revealed that the K-OMS-2 surface contained many uniformly cylindrical
      aggregates less than about 40 nm in diameter and about 80-100 nm in length.
      Besides, a high specific surface area of 129 m2/g and average pore size of 45.47
      nm were recorded. According to the TGA/DTA analysis, the prepared catalyst
      revealed high thermal stability. The maximum metronidazole degradation (95.36%)
      was evident at conditions of pH = 3, catalyst mass = 0.97 g/L, contact time = 200
      min, and metronidazole concentration = 20 mg/L. Metronidazole did not form a
      complex with nitrate, fluoride, sulfate, or hardness. These ions exerted a
      negligible effect on metronidazole reduction using the K-OMS-2 catalyst, except
      for hardness, which reduced the removal efficiency of metronidazole by 17%. The
      FTIR and LC-MS revealed a complex mechanism involved in the metronidazole
      degradation by the K-OMS-2 involving the formation of an amino group, a
      hydroxyelated compound via N-denitration, and hydrogenation process on the K-OMS
      2 catalyst surface.

PMID- 30284714
TI  - Peri-anaesthetic cardiac arrest with administration of enalapril, spironolactone
      and beta-blocker.
AB  - none.

PMID- 30284710
TI  - Particulate matter air pollution and respiratory impact on humans and animals.
AB  - Air pollution is now fully acknowledged to be a public health problem and a
      social issue. Particulate matter (PM) concentration has been linked with several
      clinical manifestations of pulmonary and cardiovascular diseases and is
      associated with morbidity and mortality induced by respiratory diseases both in
      human and animals. Current research on airborne particle-induced health effects
      investigates the critical characteristics of particulate matter that determine
      their biological effects. Scientific evidence assessed that the size of the
      airborne particles and their surface area determine the potential to elicit
      inflammatory injury, oxidative damage, and other biological effects. Thus, the
      present review paper aims to summarize the current evidences and findings on the
      effect of air pollution on lung function in both humans and animals.

PMID- 30284715
TI  - Postoperative pain after spinal surgery in the paediatric population.
AB  - INTRODUCTION: Postoperative pain is a major aftereffect of surgery. Especially
      severe occurs after extensive operations within the spine. The goal of the study
      was to investigate the laboratory predictive factors of intensive postoperative
      pain in children undergoing extensive surgery Patients and methods: We recruited
      41 children, age median 13 years (IQR:10-15 years) undergoing extensive spine
      surgery. The subjects were divided into two groups based on the intensity of
      postoperative pain measured using the 10-point numerical rating scale (NRS),
      visual analog scale (VAS) or faces pain scale-revised (FPS-R). Patients with a
      score of 5 or higher were included in the study group and those with NRS of less
      than 5 were included in the control group. We collected detailed clinical and
      laboratory data before, during and after surgery. RESULTS: The highest intensity
      of pain was observed in the first 6 hours after surgery. The postoperative pain
      was associated with a higher drop in hemoglobin concentration and hematocrit
      level in peri-operative period (p=0.006 and p=0.019 respectively) as well as
      higher changes in mean arterial pressure during surgery. Additionally, we found
      that children with intensive pain had higher total protein concentration after
      surgery. CONCLUSIONS: We reported that the drop in hemoglobin and hematocrit
      level, fluctuation in mean arterial pressure as well as total protein
      concentration could be useful prognostic factors of early postoperative pain. < p
      > < /p >.

PMID- 30284716
TI  - A case report of inadvertent intranasal submucosal injection of concentrated
      epinephrine with no long-term sequelae.
AB  - < p > < /p >.

PMID- 30284717
TI  - R-spondin 2 promotes osteoblastic differentiation of immature human periodontal
      ligament cells through the Wnt/beta-catenin signaling pathway.
AB  - OBJECTIVE: In this study, we measured the expression of R-spondin 2 (RSPO2) in
      periodontal ligament (PDL) tissue and cells. Further, we examined the effects of
      RSPO2 on osteoblastic differentiation of immature human PDL cells (HPDLCs).
      BACKGROUND: R-spondin (RSPO) family proteins are secreted glycoproteins that play
      important roles in embryonic development and tissue homeostasis through
      activation of the Wnt/beta-catenin signaling pathway. RSPO2, a member of the RSPO
      family, has been reported to enhance osteogenesis in mice. However, little is
      known regarding the roles of RSPO2 in PDL tissues. METHODS: Expression of RSPO2
      in rat PDL tissue and primary HPDLCs was examined by immunohistochemical and
      immunofluorescence staining, as well as by semiquantitative RT-PCR. The effects
      of stretch loading on the expression of RSPO2 and Dickkopf-related protein 1
      (DKK1) were assessed by quantitative RT-PCR. Expression of receptors for RSPOs,
      such as Leucine-rich repeat-containing G-protein-coupled receptors (LGRs) 4, 5,
      and 6 in immature human PDL cells (cell line 2-14, or 2-14 cells), was
      investigated by semiquantitative RT-PCR. Mineralized nodule formation in 2-14
      cells treated with RSPO2 under osteoblastic inductive condition was examined by
      Alizarin Red S and von Kossa stainings. Nuclear translocation of beta-catenin and
      expression of active beta-catenin in 2-14 cells treated with RSPO2 were assessed
      by immunofluorescence staining and Western blotting analysis, respectively. In
      addition, the effect of Dickkopf-related protein 1 (DKK1), an inhibitor of
      Wnt/beta-catenin signaling, was also examined. RESULTS: Rat PDL tissue and HPDLCs
      expressed RSPO2, and HPDLCs also expressed RSPO2, while little was found in 2-14
      cells. Expression of RSPO2 as well as DKK1 in HPDLCs was significantly
      upregulated by exposure to stretch loading. LGR4 was predominantly expressed in 2
      14 cells, which expressed low levels of LGR5 and LGR6. RSPO2 enhanced the
      Alizarin Red S and von Kossa-positive reactions in 2-14 cells. In addition, DKK1
      suppressed nuclear translocation of beta-catenin, activation of beta-catenin, and
      increases of Alizarin Red S and von Kossa-positive reactions in 2-14 cells, all
      of which were induced by RSPO2 treatment. CONCLUSION: RSPO2, which is expressed
      in PDL tissue and cells, might play an important role in regulating the
      osteoblastic differentiation of immature human PDL cells through the Wnt/beta
      catenin signaling pathway.

PMID- 30284718
TI  - Pyrexia in juvenile dogs: a review of 140 referred cases.
AB  - OBJECTIVES: To describe the presentation, influence of previous treatment and
      diagnosis in juvenile dogs presenting with pyrexia to a UK referral centre.
      MATERIALS AND METHODS: Clinical records of dogs aged 1 to 18 months presenting
      with a problem list including pyrexia (>=?39?2 degrees C) that was reproducible
      during referral hospitalisation were retrospectively reviewed. Signalment,
      history - including previous treatment, clinical examination findings and
      diagnosis were recorded. Diagnoses were categorised as non-infectious
      inflammatory, infectious, congenital, neoplastic and miscellaneous. The influence
      of previous treatment on the ability to reach a final diagnosis was analysed.
      RESULTS: A total of 140 cases were identified. Diagnosis was reached in 115
      cases. Non-infectious inflammatory disease was identified in 91 cases (79%),
      infectious disease in 19 cases (17%), a congenital disorder in four dogs (3%) and
      neoplasia in one dog (1%). Breeds most commonly identified were Border collies
      (17/140; 12%), beagles (16/140; 11%), Labrador retrievers (11/140; 8%), springer
      spaniels (9/140; 6%) and cocker spaniels (8/140; 6%). Before presentation, most
      dogs had received antibiotics (83/140; 59%), non-steroidal anti-inflammatory
      drugs (84/140; 60%) or steroids (9/140; 6%), either alone or in combination.
      Neither antibiotics nor non-steroidal anti-inflammatory drugs influenced the
      ability to reach a diagnosis. Steroid-responsive meningitis-arteritis comprised
      55 of 91 (60%) individuals of the non-infectious inflammatory cohort. All four
      dogs diagnosed with congenital disorders were Border collies. CLINICAL
      SIGNIFICANCE: Non-infectious inflammatory disease, particularly steroid
      responsive meningitis-arteritis, immune-mediated polyarthritis and metaphyseal
      osteopathy, was commonly diagnosed in this population of pyrexic juvenile dogs.

PMID- 30284719
TI  - Association between missed canals and apical periodontitis.
AB  - AIM: To evaluate the frequency of post-treatment apical periodontitis associated
      with root filled teeth with at least one untreated root canal. METHODOLOGY: Eight
      hundred and seven cone beam computed tomography images containing at least one
      root filled tooth were selected from a collection of 1543 images from Brazilian
      individuals. Scans were taken using ICAT Classic devices (Imaging Sciences,
      Hatfield, PA, USA) in a private oral radiology clinic from January to April 2015.
      All root filled teeth were analysed for the presence of missed canals and apical
      periodontitis. The chi-square and odds ratio tests were used to verify if there
      were an association and risk relationship between the occurrence of untreated
      canals and apical periodontitis. RESULTS: A total of 2294 teeth with evidence of
      root fillings were identified. Two hundred and eighty-one teeth had at least one
      untreated missed canal (12%). The frequency of apical periodontitis in teeth with
      at least one untreated canal was significantly greater in comparison to teeth
      with all canals treated (274/281, 98% versus 1736/2013, 86%) (P < 0.01). The odds
      for apical periodontitis to be present was 6.25 times greater for teeth with an
      untreated canal. The mesiobuccal roots of maxillary first molars had the greatest
      frequency of untreated canals (114/154, 74%), with the second mesiobuccal canal
      being the most frequently missed (n = 106/114, 93%). CONCLUSION: Root filled
      teeth with at least one missed canal had a high prevalence of post-treatment
      apical periodontitis.

PMID- 30284720
TI  - Income inequality, perceived competitiveness, and approach-avoidance motivation.
AB  - OBJECTIVE: Scholars disagree on whether income inequality has incentive or
      disincentive effects. In the present research, we move beyond such debate and
      focus on the motivational processes that income inequality predicts. First,
      income inequality makes economic stratification salient; therefore, it should
      promote perceived competitiveness. Second, competitiveness can be appraised as
      both a challenge and a threat; therefore, it should promote both approach and
      avoidance motivation. METHOD: In three studies (N = 2,543), U.S. residents from
      various ZIP codes reported the extent to which they perceived competitiveness in
      their town/city (Studies 1-3), as well as their economic achievement goals,
      achievement motives, and self-regulatory foci (Studies 2-3). RESULTS: Level of
      local income inequality was found to be a positive predictor-via increased
      perceived competitiveness-of other-approach economic goals, need for achievement,
      and promotion focus, as well as other-avoidance economic goals, fear of failure
      (specifically, the shame/embarrassment component), and prevention focus.
      Furthermore, actual and perceived income inequality were positively correlated.
      CONCLUSIONS: The conceptual and empirical work herein is the first to show how
      the economic environment predicts individuals' perceptions of competitiveness,
      influencing personal goals, motives, and orientations. It provides a more nuanced
      perspective on the implications of income inequality than perspectives currently
      available.

PMID- 30284721
TI  - Proteomic profile of root canal contents in teeth with post-treatment endodontic
      disease.
AB  - AIM: To characterize the proteome of 20 root canals in teeth with post-treatment
      endodontic disease using mass spectrometry and to correlate the identified
      proteins with clinical features. METHODOLOGY: Twenty patients with radiographic
      evidence of apical periodontitis and need for root canal re-treatment were
      selected. Samples from the root canal contents were collected and processed using
      two-dimensional capillary nano-flow liquid chromatography and electrospray
      ionization tandem mass spectrometry. The acquired spectra were separately
      searched against specific protein database. The results obtained were analysed
      using descriptive statistics. Additionally, Pearson's chi-square test or one
      sided Fisher's exact test, as appropriate, was chosen to examine the null
      hypothesis that there is no relationship between each clinical feature and the
      presence of specific microbial or human proteins. Significance levels were set at
      5% (P < 0.05). RESULTS: A total of 1153 human and 720 microbial UniProt accession
      numbers corresponding to proteins were recovered. The greater prevalence of
      proteins was related to biological functions, such as cellular and metabolic
      processes. A considerable number of microbial proteins with clinical relevance
      functions, such as pathogenesis/virulence, proteolysis, cell adhesion and drug
      resistance, were detected. Common endodontic pathogens related to post-treatment
      endodontic disease such as Enterococcus spp., Propionibacterium spp. and
      Streptococcus spp. were associated with 23, 40 and 94 distinct proteins,
      respectively. As for human proteins, many factors related to the immune system
      process were detected. No significant correlations were found between microbial
      and human proteins and the clinical features investigated (P > 0.05).
      CONCLUSIONS: A considerable number of microbial and human proteins were
      identified using proteomic analyses, being mainly related to processes indicating
      cell viability. No significant correlation was found between proteins and
      clinical features. These findings suggest a network of important microbial
      pathogenic functions that may be responsible for the host immune system response.

PMID- 30284722
TI  - Association of LTA gene haploblock with periodontal disease in Italian adults.
AB  - BACKGROUND: Periodontitis is a common oral disease caused by host inflammatory
      response towards bacteria biofilm. The chronic activation of immune response
      leads to destruction of teeth supporting tissue, bone loss and tooth detachment.
      Different factors could be involved in the development and severity of the
      disease; among them the host genetic background should be considered. OBJECTIVES:
      In our study, we analysed haploblocks in a genomic region within major
      histocompatibility complex (MHC) locus aimed at disclosing a possible correlation
      with the risk of periodontal disease in 602 adult subjects from North-East Italy.
      RESULTS: The CTTAC haploblock (formed by LTA-rs2857709, LTA-rs2844484, LTA-
      rs2229094, LTA-rs2229092 and LTA-rs1041981 polymorphisms) correlated with
      protection towards periodontitis condition, after regression analysis including
      age and smoking status as covariates (P-value = 0.015). CONCLUSION: Our results
      suggest that a haplotype within LTA gene (encoding for lymphotoxin alpha) is
      involved in the susceptibility towards chronic periodontitis.

PMID- 30284723
TI  - Effect of client complaints on small animal veterinary internists.
AB  - OBJECTIVES: To investigate the effect of client complaints on small animal
      veterinary internists' welfare, job satisfaction and medical practices. MATERIALS
      AND METHODS: Cross-sectional anonymous survey study. Between February 1 and March
      31, 2017, a web-based questionnaire was made available through the American
      College Veterinary Internal Medicine sub-specialty Small Animal Internal Medicine
      E-mail List Serve. RESULTS: A total of 92 completed surveys were available for
      review. Fifty-nine (64?1%) respondents received a client complaint during the
      previous 6 months with cost of care the most common reason (53?3%). Eighty-nine
      (96?7%) respondents worry about client complaints being made against them with 33
      (35?8%) stating they worry "most of the time" or "all of the time." Thirty-two
      (34?8%) reported being verbally assaulted by a client in the previous 6 months
      and 27 (29?4%) reported being threatened with litigation during the previous 6
      months. Sixty-six (71?7%) have reported changing the way they practice medicine
      to avoid a client complaint and 40 (43?5%) have considered changing their career
      because of complaints made against them. CLINICAL RELEVANCE: Client complaints
      are a frequent problem among small animal veterinary internists that have
      detrimental effects on job satisfaction, psychological distress and medical
      practices.

PMID- 30284724
TI  - Low protein diets for non-diabetic adults with chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is defined as reduced function of the
      kidneys present for 3 months or longer with adverse implications for health and
      survival. For several decades low protein diets have been proposed for
      participants with CKD with the aim of slowing the progression to end-stage kidney
      disease (ESKD) and delaying the onset of renal replacement therapy. However the
      relative benefits and harms of dietary protein restriction for preventing
      progression of CKD have not been resolved. This is an update of a systematic
      review first published in 2000 and updated in 2006 and 2009. OBJECTIVES: To
      determine the efficacy of low protein diets in preventing the natural progression
      of CKD towards ESKD and in delaying the need for commencing dialysis treatment in
      non-diabetic adults. SEARCH METHODS: We searched the Cochrane Kidney and
      Transplant Register of Studies up to 2 March 2018 through contact with the
      Information Specialist using search terms relevant to this review. Studies in the
      Register are identified through searches of CENTRAL, MEDLINE, and EMBASE,
      conference proceedings, the International Clinical Trials Register (ICTRP) Search
      Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) or quasi RCTs in which adults with non-diabetic chronic
      kidney disease (stages 3 to 5) not on dialysis were randomised to receive a very
      low protein intake (0.3 to 0.4 g/kg/d) compared with a low protein intake (0.5 to
      0.6 g/kg/d) or a low protein intake compared with a normal protein intake (>= 0.8
      g/kg/d) for 12 months or more. DATA COLLECTION AND ANALYSIS: Two authors
      independently selected studies and extracted data. For dichotomous outcomes
      (death, all causes), requirement for dialysis, adverse effects) the risk ratios
      (RR) with 95% confidence intervals (CI) were calculated and summary statistics
      estimated using the random effects model. Where continuous scales of measurement
      were used (glomerular filtration rate (GFR), weight), these data were analysed as
      the mean difference (MD) or standardised mean difference (SMD) if different
      scales had been used. The certainty of the evidence was assessed using GRADE.
      MAIN RESULTS: We identified an additional six studies to include 17 studies with
      2996 analysed participants (range 19 to 840). Four larger multicentre studies
      were subdivided according to interventions so that the review included 21
      separate data sets. Mean duration of participant follow-up ranged from 12 to 50
      months.Random sequence generation and allocation concealment were considered at
      low risk of bias in eleven and nine studies respectively. All studies were
      considered at high risk for performance bias as they were open-label studies. We
      assessed detection bias for outcome assessment for GFR and ESKD separately. As
      GFR measurement was a laboratory outcome all studies were assessed at low risk of
      detection bias. For ESKD, nine studies were at low risk of detection bias as the
      need to commence dialysis was determined by personnel independent of the study
      investigators. Five studies were assessed at high risk of attrition bias with
      eleven studies at low risk. Ten studies were at high risk for reporting bias as
      they did not include data which could be included in a meta-analysis. Eight
      studies reported funding from government bodies while the remainder did not
      report on funding.Ten studies compared a low protein diet with a normal protein
      diet in participants with CKD categories 3a and b (9 studies) or 4 (one study).
      There was probably little or no difference in the numbers of participants who
      died (5 studies 1680 participants: RR 0.77, 95% CI 0.51 to 1.18; 13 fewer deaths
      per 1000; moderate certainty evidence). A low protein diet may make little or no
      difference in the number of participants who reached ESKD compared with a normal
      protein diet (6 studies, 1814 participants: RR 1.05, 95% CI 0.73 to 1.53; 7 more
      per 1000 reached ESKD; low certainty evidence). It remains uncertain whether a
      low protein diet compared with a normal protein intake impacts on the outcome of
      final or change in GFR (8 studies, 1680 participants: SMD -0.18, 95% CI -0.75 to
      0.38; very low certainty evidence).Eight studies compared a very low protein diet
      with a low protein diet and two studies compared a very low protein diet with a
      normal protein diet. A very low protein intake compared with a low protein intake
      probably made little or no difference to death (6 studies, 681 participants: RR
      1.26, 95% CI 0.62 to 2.54; 10 more deaths per 1000; moderate certainty evidence).
      However it probably reduces the number who reach ESKD (10 studies, 1010
      participants: RR 0.65, 95% CI 0.49 to 0.85; 165 per 1000 fewer reached ESKD;
      moderate certainty evidence). It remains uncertain whether a very low protein
      diet compared with a low or normal protein intake influences the final or change
      in GFR (6 studies, 456 participants: SMD 0.12, 95% CI -0.27 to 0.52; very low
      certainty evidence).Final body weight was reported in only three studies. It is
      uncertain whether the intervention alters final body weight (3 studies, 89
      participants: MD -0.40 kg, 95% CI -6.33 to 5.52; very low certainty
      evidence).Twelve studies reported no evidence of protein energy wasting
      (malnutrition) in their study participants while three studies reported small
      numbers of participants in each group with protein energy wasting. Most studies
      reported that adherence to diet was satisfactory. Quality of life was not
      formally assessed in any studies. AUTHORS' CONCLUSIONS: This review found that
      very low protein diets probably reduce the number of people with CKD 4 or 5, who
      progress to ESKD. In contrast low protein diets may make little difference to the
      number of people who progress to ESKD. Low or very low protein diets probably do
      not influence death. However there are limited data on adverse effects such as
      weight differences and protein energy wasting. There are no data on whether
      quality of life is impacted by difficulties in adhering to protein restriction.
      Studies evaluating the adverse effects and the impact on quality of life of
      dietary protein restriction are required before these dietary approaches can be
      recommended for widespread use.

PMID- 30284725
TI  - His bundle pacing: Still much to learn.

PMID- 30284726
TI  - Autoimmune heparin-induced thrombocytopenia of delayed onset: a clinical
      challenge.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) usually appears at 5 to 10
      days after initiation of heparin. Autoimmune HIT can arise after discontinuation
      of heparin treatment (delayed-onset HIT) or without any preceding heparin
      exposure (spontaneous HIT syndrome). CASE REPORT: This case presents a course of
      autoimmune HIT with delayed onset. The patient was hospitalized due to influenza
      pneumonia and received low-molecular-weight heparin thromboprophylaxis for 9
      days. Seven days after discharge, she was readmitted because of a cerebral sinus
      vein thrombosis and severe thrombocytopenia. Intracranial bleeding and brain
      infarction caused her death. DISCUSSION: Autoimmune HIT was confirmed by
      functional heparin-induced platelet (PLT) activation test. Intracranial bleeding
      prevented continuous and effective anticoagulation. PLT transfusions were given,
      although they are generally advised against in HIT patients due to potential risk
      of thromboembolic events. CONCLUSION: This case presents that testing PLT
      activating antibodies both in the presence and in the absence of current heparin
      treatment helps to diagnose patients with autoimmune HIT. There is conflicting
      evidence to refuse PLT transfusion when HIT is complicated with life-threatening
      bleeding.

PMID- 30284727
TI  - Multicenter reproducibility of quantitative susceptibility mapping in a
      gadolinium phantom using MEDI+0 automatic zero referencing.
AB  - PURPOSE: To determine the reproducibility of quantitative susceptibility mapping
      at multiple sites on clinical and preclinical scanners (1.5 T, 3 T, 7 T, and 9.4
      T) from different vendors (Siemens, GE, Philips, and Bruker) for standardization
      of multicenter studies. METHODS: Seven phantoms distributed from the core site,
      each containing 5 compartments with gadolinium solutions with fixed
      concentrations between 0.625 mM and 10 mM. Multi-echo gradient echo scans were
      performed at 1.5 T, 3 T, 7 T, and 9.4 T on 12 clinical and 3 preclinical
      scanners. DICOM images from the scans were processed into quantitative
      susceptibility maps using the Laplacian boundary value (LBV) and MEDI+0 automatic
      uniform reference algorithm. Region of interest (ROI) analyses were performed by
      a physicist to determine agreement between results from all sites. Measurement
      reproducibility was assessed using regression, Bland-Altman plots, and the intra
      class correlation coefficient (ICC). RESULTS: Quantitative susceptibility mapping
      (QSM) from all scanners had similar, artifact-free visual appearance. Regression
      analysis showed a linear relationship between gadolinium concentrations and
      average QSM measurements for all phantoms (y = 350x - 0.0346, r2 >0.99). The SD
      of measurements increased almost linearly from 32 ppb to 230 ppb as the measured
      susceptibility increased from 0.26 ppm to 3.56 ppm. A Bland-Altman plot showed
      the bias, upper, and lower limits of agreement for all comparisons were -10, 
      210, and 200 ppb, respectively. The ICC was 0.991 with a 95% CI (0.973, 0.99).
      CONCLUSIONS: QSM shows excellent multicenter reproducibility for a large range of
      susceptibility values encountered in cranial and extra-cranial applications on a
      diverse set of scanner platforms.

PMID- 30284729
TI  - Rubronychia: a rose by any other name.

PMID- 30284728
TI  - Characteristics of non-melanoma skin cancers of the cutaneous perioral and
      vermilion lip treated by Mohs micrographic surgery.
AB  - BACKGROUND: The lip and surrounding perioral region are susceptible to non
      melanoma skin cancer, but the distribution of basal cell and squamous cell
      carcinoma on the cutaneous and vermilion lips has not been fully elucidated.
      OBJECTIVE: To investigate the distribution of cutaneous and vermilion lip non
      melanoma skin cancer and to better describe risk factors, anatomic location,
      treatment characteristics and oncologic outcomes. METHODS: A retrospective
      comparative case series of patients undergoing Mohs micrographic surgery (MMS) at
      a single academic centre for lip and perioral basal cell and squamous cell
      carcinoma was performed over a 5-year period. Demographics, medical
      comorbidities, surgical characteristics and recurrence status were extracted.
      RESULTS: Forty-five vermilion and 116 cutaneous lip cancers were identified.
      Basal cell carcinoma (BCC) was more common in the cutaneous perioral region,
      while squamous cell carcinoma (SCC) was more common on the vermilion lip (P <
      0.001). BCCs were more common on the upper vermilion lip and SCCs were more
      common on the lower vermilion lip (P < 0.001). Within the cutaneous perioral
      region, both BCCs and SCCs were more common on the upper perioral surface (P =
      0.002). Male gender was associated with lower lip SCC (P = 0.015). Smoking,
      immunosuppression, anticoagulant use and hydrochlorothiazide use were not
      associated with cancer type or location. Recurrences were rare, but more common
      in vermilion lip cancers (6.6%) compared to perioral cutaneous cancers (0.8%).
      Outcomes for all groups were similar; BCCs of the vermilion lip had significantly
      greater mean MMS stages (P < 0.001) as did SCCs (P = 0.05). CONCLUSION: Basal
      cell carcinoma is more commonly encountered on the cutaneous lip, whereas SCC is
      more common on the vermilion lip. Within the vermilion lip, BCC favours the upper
      lip, while SCC favours the lower lip. Within the cutaneous perioral region, both
      BCC and SCC favour the upper cutaneous tissue. Early stage lip cancers are
      curable by Mohs micrographic surgery with rare recurrences.

PMID- 30284730
TI  - Dynamic per slice Shimming for Simultaneous Brain and Spinal Cord fMRI.
AB  - PURPOSE: Simultaneous brain and spinal cord functional MRI is emerging as a new
      tool to study the central nervous system but is challenging. Poor B0 homogeneity
      and small size of the spinal cord are principal obstacles to this nascent
      technology. Here we extend a dynamic shimming approach, first posed by
      Finsterbusch, by shimming per slice for both the brain and spinal cord. METHODS:
      We shim dynamically by a simple and fast optimization of linear field gradients
      and frequency offset separately for each slice in order to minimize off-resonance
      for both the brain and spinal cord. Simultaneous acquisition of brain and spinal
      cord fMRI is achieved with high spatial resolution in the spinal cord by means of
      an echo-planar RF pulse for reduced FOV. Brain slice acquisition is full FOV.
      RESULTS: T2*-weighted images of brain and spinal cord are acquired with high
      clarity and minimal observable image artifacts. Fist-clenching fMRI experiments
      reveal task-consistent activation in motor cortices, cerebellum, and C6-T1 spinal
      segments. CONCLUSIONS: High quality functional results are obtained for a sensory
      motor task. Consistent activation in both the brain and spinal cord is observed
      at individual levels, not only at group level. Because reduced FOV excitation is
      applicable to any spinal cord section, future continuation of these methods holds
      great potential.

PMID- 30284731
TI  - Micronuclei frequency in urothelial cells of bladder cancer patients, as a
      biomarker of prognosis.
AB  - It has been suggested that the frequency of micronuclei (MN) in defoliated
      urothelial cells could be used as a biomarker for both the potential risk of
      bladder cancer (BC) and its progression. To prove this we have carried out a
      large study evaluating the MN frequency in a group of 383 hospital patients
      submitted to cystoscopy. From them, 77 were negative in their first cystoscopy,
      and were considered as a reference group; 79 were positive and were classified as
      patients with tumor; and 227 with previous bladder cancer submitted to follow-up
      monitoring were negative and classified as BC patients without tumor. Vesical
      washes were processed and the obtained cells were placed onto microscope slides
      for further scoring. To minimize scoring misinterpretations, cells were stained
      with DAPI, and observed in a fluorescence microscope. Results indicated that
      patients with BC presented higher incidence of MN than controls (18.29 +/- 10.04
      vs. 14.40 +/- 8.49, P = 0.010, respectively). When individuals with BC were
      classified depending on whether the BC was a primary or a recidivated tumor,
      those patients with recurrent BC presented a higher frequency of MN than those
      where BC was detected for the first time (19.22 +/- 9.59 vs. 16.60 +/- 10.78,
      respectively); nevertheless, this increase did not reach statistical
      significance. Finally, a positive and significant correlation was observed
      between MN frequency and the degree of the tumor (P = 0.038). All this together
      would confirm the potentiality of the MN frequency in urothelial defoliated cells
      assay to be used, at least, in the follow-up and surveillance of BC patients.
      Environ. Mol. Mutagen. (c) 2018 Wiley Periodicals, Inc.

PMID- 30284732
TI  - Thrombotic thrombocytopenic purpura relapse induced by acute hepatitis E
      transmitted by cryosupernatant plasma and successfully controlled with ribavirin.
AB  - BACKGROUND: Hepatitis E virus (HEV) can be transmitted by transfusion of any type
      of blood component, but there are few data on the potential risk of transmitting
      this virus and the associated complications. We provide evidence that HEV can be
      transmitted by cryosupernatant plasma, and that HEV infection can act as a
      trigger for thrombotic thrombocytopenic purpura (TTP). STUDY DESIGN AND METHODS:
      A patient with a history of TTP treated with plasmapheresis 2 months previously
      developed jaundice and a TTP exacerbation with purpura, thrombocytopenia,
      schistocytes, and undetectable ADAMTS-13 activity. He was diagnosed with acute
      hepatitis E and treated with ribavirin. TTP remitted with remission of HEV
      infection. RESULTS: Traceback to determine the source of the infection showed
      that 1 cryosupernatant plasma among the 99 different blood components used for
      the patient's last plasmapheresis was positive for HEV RNA, with an estimated
      viral load of 5000 to 10,000 IU/mL. Phylogenetic analysis proved the transfusion
      transmitted route of acute hepatitis E. CONCLUSION: In a patient with TTP, acute
      HEV infection transmitted by cryosupernatant plasma may trigger exacerbation of
      TTP, which can be controlled on remission of HEV infection with ribavirin.

PMID- 30284733
TI  - Legs of male fiddler crabs evolved to compensate for claw exaggeration and
      enhance claw functionality during waving displays.
AB  - Many exaggerated morphological traits evolve under sexual selection. However, the
      optimal level of exaggeration is dictated by a trade-off between natural and
      sexual selection, representing a balance between its benefits and associated
      costs. Male fiddler crabs wave an enlarged major claw during behavioural displays
      that eliminates the need for direct combat, and determines courtship outcomes.
      The outcomes of these displays often depend on claw size, exposing males to
      selection for larger claws to improve mating and combat success. Applying
      phylogenetic comparative methods to 27 fiddler crab species, we examined the
      evolution of major claw morphologies, leg morphologies, and waving displays to
      determine whether these traits coevolved to optimise functioning of the
      exaggerated claw, or to mitigate potential metabolic or locomotor costs. We found
      legs to be sexually dimorphic, with males having longer legs than females. Legs
      were also longer in species that waved laterally rather than vertically, in
      species with larger major claws, and in species whose major claws were relatively
      elongate. These results suggest that leg morphology has coevolved with claw
      enlargement to enhance functionality of the major claw during waving displays, in
      addition to compensating for any negative effects of claw size.

PMID- 30284734
TI  - Hepatic Stellate Cells (HSCs) and Retinoids: Towards A Much More Defined
      Relationship.
AB  - The role of hepatic stellate cells (HSCs) in the development of fibrosis,
      cirrhosis, and hepatocellular carcinoma (HCC) has long been the focus of
      considerable research interest. There also has been longstanding interest in
      understanding the molecular processes underlying how HSCs store retinoids
      (vitamin A and its natural and synthetic analogs) and how the availability of
      these transcriptional regulators may influence HSC biology. This article is
      protected by copyright. All rights reserved.

PMID- 30284736
TI  - Editorial: aminosalicylates in Crohn's disease-prevalence, risks, costs and time
      to reassess? Authors' reply.

PMID- 30284735
TI  - Nonhormonal selective estrogen receptor modulator 1-(2-[4-{(3R,4S)-7-Methoxy-2, 2
      dimethyl-3-phenyl-chroman-4yl}phenoxy]ethyl)pyrrolidine hydrochloride
      (ormeloxifene hydrochloride) for the treatment of breast cancer.
AB  - Breast cancer is the most common type of diagnosed cancers in women, difficult to
      treat, and has received international attention because of its aggressive nature
      and inherent drug resistance mechanisms. Development of a better selective
      estrogen receptor modulator with good therapeutic profile and less toxicity is
      very crucial in this scenario. This study was undertaken to evaluate and compare
      the in vitro and in vivo antitumor activities of ormeloxifene with other
      clinically used breast cancer drugs. Cytotoxic activity of ormeloxifene was
      compared with standard drugs, 4-hydroxytamoxifene and Adriamycin. Ormeloxifene
      (50 MUM) concentration showed cytotoxicity of 75% and 82% in MDAMB-231 and 24%
      and 80% in MCF-7 cells, respectively, after 72 and 144 hr of incubation as
      displayed by cell viability assay. The same concentration of ormeloxifene was
      shown to exert 74% caspase-7 activation in MCF-7 cells after 24 hr of incubation
      by fluorescence resonance energy transfer assay. Cell cycle analysis proved that
      there was an increase in sub-G1 peak to 64.4% and 33.9% in MDAMB-231 and MCF-7
      cells, respectively, after treatment using ormeloxifene (50 MUM) for 48 hr. The
      nonobese diabetic-severe combined immunodeficiency mice bearing tumor xenografts
      of triple negative MDAMB-231 cells treated with ormeloxifene (3 mg/kg bw) showed
      significant regression in relative tumor volume compared to control. From the
      results obtained and as evidenced from prior literature, ormeloxifene in addition
      to contraceptive use, can be repositioned for the development of an efficacious
      anticancer drug. These data present the preclinical part of a well concerted
      effort to place ormeloxifene into further clinical trials.

PMID- 30284737
TI  - Sex differences in the regulation of hepatic mitochondrial turnover following
      physical activity: do males need more quality control than females?

PMID- 30284738
TI  - Determination of permeability, plasma protein binding, blood partitioning,
      pharmacokinetics and tissue distribution of Withanolide A in rats: A
      neuroprotective steroidal lactone.
AB  - Preclinical Research & Development Withanolide A (WA), a steroidal lactone is a
      major bioactive constituent of Withania somnifera (L.) with remarkable
      neuropharmacological activity. In this study, we investigated the permeability,
      plasma protein binding (PPB), blood partitioning, intravenous (i.v.), and oral
      pharmacokinetics as well as i.v. tissue distribution (TD) of pure WA in a rat
      model. The PPB, RBCs partitioning, and permeability of WA were determined by
      Ultra Performance Liquid Chromatography (UPLC) method. However, the
      pharmacokinetics and TD of WA were evaluated by validated and sensitive liquid
      chromatography coupled mass spectrometry (LC-ESI-MS/MS) method. The PPB and
      permeability of WA were determined by equilibrium dialysis and parallel
      artificial membrane permeability assay method, respectively. The results
      demonstrated that WA has high PPB and passive permeability. Furthermore, WA was
      found to have fast equilibration between RBCs and plasma. Following i.v. (2
      mg/kg) and per-oral (25 mg/kg) administration of WA, the max concentration (Cmax
      ) in plasma was found as 85.53 +/- 6.54 and 48.04 +/-5.78 ng/mL, respectively.
      The TD study results indicated that WA has a rapid and wide TD. The maximum
      concentration in various tissues was found in following order: Clung  > Cliver  >
      Ckidney  ~ Cspleen  > Cheart  > Cbrain . The preclinical in vitro, as well as
      pharmacokinetics and TD results, are anticipated to support the future
      preclinical and clinical application of WA.

PMID- 30284739
TI  - Investigation of the antimicrobial and anticancer activity of
      aminonaphthoquinones.
AB  - In this study, we report on the inhibitory activity of synthesized
      aminonaphthoquinones against two bacterial and one fungal species to determine
      their antimicrobial properties. A minimum inhibitory concentration (MIC) of 7.8
      MUg/mL was obtained against the fungus, Candida albicans, which was better than
      that of Amphotericin B (MIC = 31.25 MUg/mL). Escherichia coli (Gram -), was
      inhibited at a MIC of 23.4 MUg/mL and Staphylococcus aureus (Gram +) at a MIC of
      31.3 MUg/mL. The aminonaphthoquinones were also screened against HCT116 colon,
      PC3 prostate and HepG2 liver cancer cell lines to evaluate their cytostatic
      effects. They had potent activity (GI50  = 5.87-9.90 MUM) which was about three-6
      fold better than that of parthenolide (GI50  = 25.97 MUM) against the prostate
      cancer cell line. These compounds were generally more selective for cancer cells
      than for normal human lung fetal fibroblasts (WI-38). Hit, Lead & Candidate
      Discovery.

PMID- 30284740
TI  - Habits and risk perception associated with sun exposure in vitiligo patients
      according to their participation in a patients' organization.

PMID- 30284741
TI  - Probiotics alter the immune response of gingival epithelial cells challenged by
      Porphyromonas gingivalis.
AB  - BACKGROUND AND OBJECTIVE: Although previous studies revealed the potential use of
      probiotics in the control of periodontitis, little is known about their
      interactions with gingival epithelial cells (GECs). Since GECs comprise the first
      defense in the subgingival microenvironment, the aim of this study was to
      evaluate the effect of probiotic lactobacilli and bifidobacteria strains on OBA-9
      cells challenged with Porphyromonas gingivalis. METHODS: Immortalized human GECs
      (OBA-9) were challenged with live P. gingivalis (strains W83 and ATCC33277) and
      co-infected with one of 12 tested probiotic strains at a multiplicity of
      infection (MOI) of 1:1000 for 2 hours. Bacterial adhesion and invasion were
      determined by antibiotic exclusion analysis and CFU counting. OBA-9 viability was
      assessed by MTT assay, and levels of inflammatory mediators (TNF-alpha, IL-1beta,
      and CXCL8) in the supernatants were determined by ELISA. The expression of genes
      encoding Toll-like receptors (TLR2, TLR4) was evaluated by RT-qPCR. RESULTS: Both
      strains of P. gingivalis were able to adhere and invade OBA-9 cells, with
      significant loss in cell viability, increase in the levels of TNF-alpha and IL
      1beta, and upregulation of TLR4. However, co-infection with probiotics attenuated
      these effects in P. gingivalis challenged GECs. Most probiotics maintained OBA-9
      viability and reduced pathogens adhesion and invasion. Furthermore, probiotics
      were able to adhere to GECs, which was enhanced for most strains in the presence
      of P. gingivalis. The synthesis of IL-1beta and TNF-alpha by P. gingivalis in
      challenged GECs was reduced in co-culture with most of the tested probiotics,
      whereas the secretion of CXCL8 increased, and TLR4 was downregulated. CONCLUSION:
      Probiotics can alter the interaction of GECs with P. gingivalis by modulating the
      pathogen's ability to adhere and invade these cells, as well as by regulating the
      innate immune response. Such properties are strain-specific and may indicate the
      most efficient probiotics to control periodontitis.

PMID- 30284742
TI  - A genome-wide association study identifies an association between variants in
      EFCAB4B gene and periodontal disease in an Italian isolated population.
AB  - BACKGROUND AND OBJECTIVE: Periodontitis in one of the most prevalent dental
      diseases. Despite numerous studies have investigated its aetiopathogenetic
      factors, few works have focused on its genetic predisposition and most of them
      took into account only candidate genes. Therefore, we conducted a Genome Wide
      Association Study in an Italian isolated population aimed at uncovering genetic
      variants that predispose to this disorder. METHODS: Diagnosis of chronic
      periodontitis was made following the criteria of the American Academy of
      Periodontology. Patients with chronic periodontitis were grouped into different
      categories: slight, severe, localized and generalized. A control group composed
      by people without signs of periodontitis or gingivitis was defined. DNA was
      genotyped using 370k Illumina chips. Linear mixed model regression was used to
      test the association between each single nucleotide polymorphism (SNP)
      (independent variable) and the periodontitis status (dependent variable),
      controlling for confounders sex, age and smoking. The genomic kinship matrix was
      also used as random effect. RESULTS: Four SNPs on the gene EFCAB4B resulted
      significantly associated to localized periodontitis (P < 5 * 10-8 ), with the
      best hit on the rs242016 SNP (P = 1.5 * 10-8 ). CONCLUSION: We have identified a
      novel significant association between the EFCAB4B gene and localized
      periodontitis. These results open a new perspective in the understanding of
      genetic factors contributing to this common disorder.

PMID- 30284743
TI  - [CONGENITAL MALFORMATION: BILIARY ATRESIA].
AB  - Congenital anomalies of biliary tract development are frequent causes of
      lingering course of physiologic jaundice which need timely verification of
      diagnosis followed by surgical treatment. Clinical observation of biliary atresia
      in a 10-month-old girl permits to accent pediatricians' attention to
      peculiarities of clinical picture, diagnosis and techniques for treatment of this
      pathology.

PMID- 30284744
TI  - RANZCOG Fellows' adherence to guidelines following cytological prediction of
      cervical adenocarcinoma-in-situ: Cause for concern?
AB  - BACKGROUND: For Australian women with screen-detected adenocarcinoma-in-situ
      (AIS), an excisional biopsy is mandatory for further assessment, treatment, and
      to exclude the presence of cervical adenocarcinoma. The only exclusion to this
      rule is if the woman has a clinically evident invasive cervical malignancy.
      Excisional treatments should be tailored according to a patient's age and future
      obstetric needs. To date, practitioner compliance with this recommendation has
      not been investigated. AIMS: To investigate clinical management for patients with
      a cytological test result predicting AIS. Secondary aims were to report the most
      severe histological findings of excisional biopsy specimens following cytological
      prediction of AIS and investigate treatment outcomes for conservatively managed
      patients with biopsy-confirmed AIS. MATERIALS AND METHODS: A retrospective,
      population-based cohort study was conducted. Cases were ascertained from the
      Tasmanian and Western Australia Cervical Screening Registries. Cytology and
      histology results for women with an index cervical smear reporting AIS from 2001
      to 2012 were reviewed. RESULTS: Three hundred and twenty-one women (age range 18
      69 years) had an index smear reporting AIS. Cervical cancer was diagnosed in 62
      (19.3%) patients within the study cohort. Twenty-one of 321 patients (6.7%) were
      not initially managed according to the 2005 NHMRC Guidelines for the management
      of asymptomatic women with screen-detected abnormalities, including two women
      diagnosed with an occult cancer following a total hysterectomy. CONCLUSIONS: A
      minority of women were not managed in accordance with guidelines. This is of
      concern given that nearly one in five women with a smear predicting AIS had a
      final diagnosis of cervical cancer.

PMID- 30284745
TI  - A consensus opinion amongst stakeholders as to benefits of obstructive sleep
      apnoea treatment for cardiovascular health.
AB  - BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) is a prevalent sleep
      disorder associated with increased cardiovascular morbidity and mortality.
      Whether treatment of OSA improves cardiovascular risk remains controversial. Our
      aim was to determine a consensus opinion of key sleep medicine stakeholder groups
      as to the cardiovascular benefits of treating moderate-severe OSA. METHODS: A
      multidisciplinary panel was assembled from representatives from the Australasian
      Sleep Association, Sleep Health Foundation, Australasian Sleep Technologists
      Association, the Sleep Health Foundation Business Council and the Sleep Disorders
      Australia patient support group. Three statements reflecting areas of controversy
      related to cardiovascular benefits of OSA treatment were created. A modified
      RAND/UCLA appropriateness methodology was applied determining the panel's level
      of consensus and agreement with each statement. RESULTS: Voting results indicated
      the panel: (1) remained unsure whether moderate-severe OSA treatment improves
      rates of cardiovascular events/death, (2) agreed that moderate-severe OSA
      treatment improves blood pressure in patients with hypertension and (3) mostly
      agreed that moderate-severe OSA treatment improves left ventricular function in
      patients with heart failure. Consensus of opinion was achieved for statements (1)
      and (2), but was narrowly missed for statement (3). CONCLUSION: The panel
      believed that findings from large-scale randomized trials indicate that treatment
      of moderate-severe OSA has not been established to improve cardiovascular event
      or morbidity/mortality rates. Strong evidence supports the ability of treatment
      to reduce blood pressure. Whilst many panel members believed that treatment
      improves left ventricular function, some were uncertain of the clinical
      significance of this secondary endpoint measure derived from lesser quality
      evidence.

PMID- 30284746
TI  - Factors associated with breast cancer in an Argentine city.

PMID- 30284747
TI  - A generalized multistage approach to oral and nasal intubation in infants with
      Pierre Robin sequence: A retrospective review.
AB  - BACKGROUND: Airway management in children with Pierre Robin sequence in the
      infantile period can be challenging and frequently requires specialized
      approaches. AIMS: The aim of this study was to review our experience with a
      multistage approach to oral and nasal intubation in young infants with Pierre
      Robin sequence. METHODS: After IRB approval, we reviewed 13 infants with Pierre
      Robin sequence who underwent a multistage approach to intubation in the operating
      room for mandibular distractor or gastrostomy tube placement. All patients
      underwent awake placement of either an LMA-ClassicTM #1 or ProSealTM laryngeal
      mask airway size #1. General anesthesia was induced with sevoflurane, and
      patients were relaxed with rocuronium. The laryngeal mask airway was replaced
      with an air-Q(r) 1.0. Children were then intubated through the air-Q(r) 1.0 using
      a flexible fiberoptic bronchoscope. In cases that required a nasotracheal tube,
      the oral tube was left in place while a flexible fiberoptic bronchoscope loaded
      with a similar internal diameter nasal Ring-Adair-Elwyn (RAE) tube was introduced
      into the nares. Once the scope was in proximity to the glottis, the oral tube was
      removed and the patient was intubated with the nasal RAE over the fiberscope.
      RESULTS: All 13 patients with Pierre Robin sequence were successfully intubated.
      We observed no periods of desaturation during placement and induction with the
      LMA-ClassicTM or ProSealTM laryngeal mask airway except in one patient who was in
      extremis in the neonatal intensive care unit and required emergent transport to
      the operating room with the laryngeal mask airway in place. We observed several
      brief periods of desaturation during the apneas associated with fiberoptic
      intubation. CONCLUSION: In conclusion, we were able to use a ventilation-driven,
      multistaged approach using the unique properties of different supraglottic
      airways to facilitate oral and nasal intubation in 13 infants with Pierre Robin
      sequence.

PMID- 30284748
TI  - Virtual reality for lumbar puncture in a morbidly obese patient with leukemia.
AB  - Virtual reality is an immersive technology that can provide distraction and
      anxiolysis during painful procedures. While it has been shown to be effective in
      less invasive procedures, it is underutilized in more invasive procedures. We
      describe using virtual reality for a morbidly obese patient with leukemia
      undergoing lumbar puncture. The use of virtual reality reduced the amount of
      analgesics and anxiolytics and the procedure and recovery times compared with no
      virtual reality.

PMID- 30284749
TI  - Dental hypomineralization treatment: A systematic review.
AB  - INTRODUCTION: Defects in the maturation stage of amelogenesis result in a normal
      volume of enamel but insufficient mineralization, called hypomineralization.
      Molar-incisor hypomineralization (MIH), amelogenesis imperfecta and dental
      fluorosis (DF) are examples of such defects. OBJECTIVE: To evaluate the
      effectiveness of the treatments applied to the different forms of dental
      hypomineralization. MATERIALS AND METHODS: PubMed, Scopus, Cochrane Library, Web
      of Science, and Embase were screened. The research was limited to studies
      published in English, Spanish, and Portuguese, until May 30, 2018. The research
      question was formulated following the Population, Intervention, Comparison,
      Outcome strategy. The quality of the methodology of each article was evaluated
      employing the Cochrane Handbook for Systematic Reviews. RESULTS: From the initial
      research, 7895 references were obtained, of which 33 were included in the
      systematic review. The following treatments were reported: desensitizing and
      remineralizing products, resin infiltration, restorations, fissure sealants,
      tooth bleaching, enamel microabrasion and calcium, and vitamins supplements.
      CONCLUSIONS: Although the results are suggestive, there is a clear need for a
      greater uniformity of the methodologies, thus allowing for the development of
      clinical guidelines. Nevertheless, it was possible to identify several effective
      treatments for teeth with MIH (arginine pastes or fluoride varnishes) and DF
      (tooth bleaching and/or enamel microabrasion). CLINICAL SIGNIFICANCE: Because
      MIH, amelogenesis imperfecta, and DF are commonly seen in dental daily practice,
      it is extremely important to analyze the literature regarding its treatment.

PMID- 30284750
TI  - Symmetrical acral keratoderma revisited: proposal for a new term, 'pigmented
      carpotarsal hyperkeratosis'.
AB  - First reported from Taiwan mistakenly as acral acanthosis nigricans in 1991,
      pigmented carpotarsal hyperkeratosis or hyperkeratosis nigricans carpi et tarsi
      displays a peculiar distribution of velvety brown-grey hyperpigmented plaques
      symmetrically on the flexural side of the wrists and ankles and on the dorsal
      sides of the hands and feet. A marked epidermal hyperkeratosis with typically
      mild acanthosis and papillomatosis is observed in histology. Whitish maceration
      upon perspiration or water exposure, with exacerbation in summer but remission in
      winter, is common. The association with obesity, endocrine disorders, atopic
      dermatitis, ichthyosis or malignancy is unknown. Familial occurrence and
      hereditary patterns are ill-defined. There is preliminary evidence indicating a
      pathogenic role of missense mutation in the transcription factor 4 gene.
      Treatment is empirical, with good outcome with topical retinoids and keratolytic
      agents. Recurrence is common, and long-term prognosis is unclear. To be
      distinguished are acral acanthosis nigricans, palmoplantar keratoderma of the
      Nagashima type, palmoplantar keratoderma of the Bothnian type and aquagenic
      palmoplantar keratoderma. Most reported cases are from Southern China and are
      predominantly observed in men between the ages of 20 and 40 years. The currently
      used term 'symmetrical acral keratoderma' is non-specific and misleading and may
      lead to global unawareness, underreporting or misdiagnosis of this phenomenon.
      Further genetic and molecular studies are required to clarify its pathogenesis
      and relation to palmoplantar keratoderma.

PMID- 30284751
TI  - Using DNA methylation to validate an electronic medical record phenotype for
      smoking.
AB  - A validated, scalable approach to characterizing (phenotyping) smoking status is
      needed to facilitate genetic discovery. Using established DNA methylation sites
      from blood samples as a criterion standard for smoking behavior, we compare three
      candidate electronic medical record (EMR) smoking metrics based on longitudinal
      EMR text notes. With data from the Veterans Aging Cohort Study (VACS), we
      employed a validated algorithm to translate each smoking-related text note into
      current, past or never categories. We compared three alternative summary
      characterizations of smoking: most recent, modal and trajectories using
      descriptive statistics and Spearman's correlation coefficients. Logistic
      regression and area under the curve analyses were used to compare the
      associations of these phenotypes with the DNA methylation sites, cg05575921 and
      cg03636183, which are known to have strong associations with current smoking. DNA
      methylation data were available from the VACS Biomarker Cohort (VACS-BC), a sub
      study of VACS. We also considered whether the associations differed by the
      certainty of trajectory group assignment (<0.80/>=0.80). Among 140 152 VACS
      participants, EMR summary smoking phenotypes varied in frequency by the metric
      chosen: current from 33 to 53 percent; past from 16 to 24 percent and never from
      24 to 33 percent. The association between the EMR smoking pairs was highest for
      modal and trajectories (rho = 0.89). Among 728 individuals in the VACS-BC, both
      DNA methylation sites were associated with all three EMR summary metrics (p <
      0.001), but the strongest association with both methylation sites was observed
      for trajectories (p < 0.001). Longitudinal EMR smoking data support using a
      summary phenotype, the validity of which is enhanced when data are integrated
      into statistical trajectories.

PMID- 30284752
TI  - Biomimetic Syntheses of (+/-)-Isopalhinine A, (+/-)-Palhinine A, and (+/-)
      Palhinine D.
AB  - The first total synthesis of isopalhinine A, as well as unified syntheses of
      palhinine A and palhinine D, were successfully accomplished by means of a
      biomimetic strategy that proceeds through a bioinspired 5/6/6/9 tetracyclic
      intermediate, which mimics the amino ketone form of palhinine D. An early-stage
      direct SN 2 cyclization to construct the nine-membered azonane ring minimized the
      transannular strain that would otherwise be increased by the twisted nature of
      the isotwistane skeleton. Then, a diastereoselective Diels-Alder reaction of a
      masked ortho-benzoquinone using the nine-membered ring as a steric shielding
      group furnished a functionalized 6/6/9 tricyclic skeleton and established the
      desired stereochemistry at the C3, C7, C12, and C15 positions in one step. A
      thiol-mediated acyl radical cyclization gave the bioinspired intermediate bearing
      three differentiated oxygen-containing functional groups, from which all three
      total syntheses could be completed in either two or three additional steps.

PMID- 30284753
TI  - TGF-beta: Master regulator of inflammation and fibrosis.

PMID- 30284754
TI  - Staining potential differences between an infiltrative resin and an esthetic,
      flowable composite.
AB  - OBJECTIVE: To compare color change magnitude of an infiltrative resin and a
      flowable composite resin after immersion in commonly consumed beverages.
      MATERIALS AND METHODS: Disks (1 * 9 mm) of a flowable composite (Filtek Supreme
      Ultra Flowable) and a resin-infiltrative product (Icon) were made. Specimens were
      dark-stored in tap water (24 hours). Baseline color parameters (CIE L*a*b*) were
      obtained using a colorimeter (Easyshade V4, VITA). Specimens were immersed (dark
      stored, 37 degrees C, 1 week) in commercial beverages: Kool-Aid, coffee, Coca
      Cola, and tap water (control). DeltaE00 between final and baseline conditions for
      each material/beverage combination was determined (N = 10/group). Initial
      analysis of variance indicated significant impact of major factors/interactions
      on DeltaE00 . Subsequently, t-tests between DeltaE00 values of restorative
      materials within each beverage was performed: alpha 0.05. RESULTS: Kool-Aid
      produced the greatest color change for flowable composite, with a DeltaE00
      significantly greater than the infiltrative product. No significant DeltaE00
      differences were noted between products immersed in coffee, however color
      parameters causing these differences were not similar. Water or Coca-Cola
      immersion showed lowest DeltaE00 values for both materials, considered visually
      imperceptible: DeltaE00 values <0.8. CONCLUSIONS: Color change potential of
      infiltrative resin or resin composite was highly dependent on beverage type, with
      no general trends observed in which material was affected more. CLINICAL
      SIGNIFICANCE: Staining potential of an infiltrative restorative resin differs
      from that of a filled, flowable composite material on a beverage-by-beverage
      basis. The potential for color change seems not related to the presence or
      absence of fillers in the restorative material.

PMID- 30284755
TI  - Non-Val30Met mutation, septal hypertrophy, and cardiac denervation in patients
      with mutant transthyretin amyloidosis.
AB  - AIMS: Mutant transthyretin (ATTRm) amyloidosis is a systemic disease caused by
      the deposition of amyloid fibrils derived from mutated transthyretin. Although
      cardiac involvement impacts the prognosis of patients with ATTRm amyloidosis, the
      incidence of cardiac events, such as bradyarrhythmia, ventricular tachycardia,
      and heart failure, has not been fully elucidated. The aim of this study was to
      evaluate the prognosis and predictors of clinical outcomes, including cardiac
      events, in patients with ATTRm amyloidosis in Japan. METHODS AND RESULTS: We
      evaluated 90 consecutive patients with ATTRm amyloidosis at Kumamoto University.
      ATTRm amyloidosis was diagnosed by the observation of both amyloid fibril
      deposition on tissue biopsy and a transthyretin mutation on sequential analysis.
      Sympathetic nerve activity was evaluated in 59 patients using 123-iodine
      metaiodobenzylguanidine (123 I-MIBG) imaging. The endpoint was a composite of all
      cause death, hospitalization for heart failure, and implantation of a pacemaker,
      implantable cardioverter defibrillator, or cardiac resynchronization therapy
      defibrillator. Sixty-seven patients had the Val30Met mutation (74%). The
      composite endpoint occurred in 23 patients (26%): all-cause death (n = 6),
      hospitalization for worsening heart failure (n = 1), and implantation of an
      implantable cardioverter defibrillator (n = 6), cardiac resynchronization therapy
      defibrillator (n = 3), or pacemaker (n = 7). The 5-year incident rate for
      clinical outcomes was 19%. In a multivariate Cox hazard analysis, age [hazard
      ratio (HR): 1.07, 95% confidence interval (95% CI): 1.01-1.12, P = 0.015], PQ
      interval (HR: 1.01, 95% CI: 1.00-1.02, P = 0.042), interventricular septum
      thickness in diastole (HR: 1.25, 95% CI: 1.09-1.42, P = 0.001), and non-Val30Met
      mutation (HR: 4.31, 95% CI: 1.53-12.16, P = 0.006) were independent predictive
      factors of clinical outcomes. Kaplan-Meier analysis demonstrated a significantly
      higher probability of the composite endpoint in the non-Val30Met group than in
      the Val30Met group (log-rank test: P = 0.002) and in patients with left
      ventricular hypertrophy than in patients without left ventricular hypertrophy
      (log-rank test: P < 0.001). In patients who underwent 123 I-MIBG imaging, a
      delayed heart-to-mediastinum (HM) ratio <1.6 was a significant predictive factor
      of the composite endpoint (HR: 4.98, 95% CI: 1.73-14.37, P = 0.003) in the
      univariate Cox hazard analyses. Kaplan-Meier curve analysis showed that a delayed
      HM ratio <1.6 was associated with a poor prognosis (log-rank test: P = 0.001).
      CONCLUSIONS: Non-Val30Met mutation, septal hypertrophy, and a delayed HM ratio
      are useful predictors of clinical outcomes in patients with ATTRm amyloidosis in
      Japan. These results suggest that it is important to evaluate cardiac involvement
      in terms of morphological (left ventricular hypertrophy) and functional (cardiac
      denervation) perspectives using echocardiography and 123 I-MIBG imaging,
      respectively.

PMID- 30284756
TI  - Ni-Catalyzed alpha-Alkylation of Unactivated Amides and Esters with Alcohols by
      Hydrogen Auto-Transfer Strategy.
AB  - A transition-metal-catalyzed borrowing hydrogen/hydrogen auto-transfer strategy
      allows the utilization of feedstock alcohols as an alkylating partner, which
      avoids the formation of stoichiometric salt waste and enables a direct and benign
      approach for the construction of C-N and C-C bonds. In this study, a nickel
      catalyzed alpha-alkylation of unactivated amides and ester (tert-butyl acetate)
      is carried out by using primary alcohols under mild conditions. This C-C bond
      forming reaction is catalyzed by a new, molecularly defined nickel(II) NNN-pincer
      complex (0.1-1 mol %) and proceeds through hydrogen auto-transfer, thereby
      releasing water as the sole byproduct. In addition, N-alkylation of cyclic amides
      under Ni-catalytic conditions is demonstrated.

PMID- 30284757
TI  - Analysis of Entamoeba histolytica Membrane Proteome Using Three Extraction
      Methods.
AB  - Entamoeba histolytica membrane proteins are important players toward the
      pathogenesis of amoebiasis, but the roles of most of the proteins are not fully
      understood. Since efficient protein extraction method is crucial for a successful
      MS analysis, three extractions methods are evaluated for the use in studying the
      membrane proteome of E. histolytica: Two commercial kits (ProteoExtract from
      Calbiochem and ProteoPrep from Sigma), and a conventional laboratory method. The
      results show that ProteoExtract and the conventional method gave higher protein
      yields compared to ProteoPrep. LC-ESI-MS/MS identifies 456, 482, and 551 membrane
      fraction proteins extracted using ProteoExtract, ProteoPrep, and a conventional
      method, respectively. In silico analysis predicts 108 (21%), 235 (45%), and 177
      (34%) membrane proteins from the extracts of ProteoExtract, ProteoPrep, and the
      conventional method, respectively. Furthermore, analysis of the cytosolic and
      membrane fractions shows the highest selectivity of the membrane proteins using
      the ProteoPrep extraction kit. Overall, this study reports 828 E. histolytica
      membrane fraction proteins that include 249 predicted membrane proteins. The data
      are available via ProteomeXchange with identifier PXD010171.

PMID- 30284758
TI  - A Supramolecular Palladium Catalyst Displaying Substrate Selectivity by Remote
      Control.
AB  - Inspired by enzymes, such as cytochrome P-450, the study of the reactivity of
      metalloporphyrins continues to attract major interest in homogeneous catalysis.
      However, little is known to take benefit from the substrate recognition
      properties of porphyrins containing additional, catalytically-relevant active
      sites. Herein, we introduce such approach using supramolecular ligands derived
      from metalloporphyrins customized with rigid, palladium-coordinating nitrile
      groups. According to different spectroscopic studies (NMR, UV-vis, X-ray
      diffraction, control experiments), the supramolecular ligands are able to
      accommodate pyridine derivatives as substrates inside the porphyrin pocket while
      the reactivity occurs in the peripheral side. By simply tuning a remote metal
      center, different binding events result in different catalyst reactivity: an
      enzyme-like feature leading to high levels of substrate selectivity when applied
      to representative palladium-catalyzed Suzuki-Miyaura reactions.

PMID- 30284759
TI  - Confirmation of spondylo-epi-metaphyseal dysplasia with joint laxity, EXOC6B
      type.

PMID- 30284760
TI  - Modelling COPD co-morbidities in preclinical models.

PMID- 30284761
TI  - A retrospective cohort study of children with spinal muscular atrophy type 2
      receiving anesthesia for intrathecal administration of nusinersen.
AB  - INTRODUCTION: Spinal muscular atrophy is characterized by loss of motor neurons
      in the anterior horn of the spinal cord with resultant proximal muscle weakness.
      Intrathecal nusinersen has revolutionized the treatment of spinal muscular
      atrophy. We reviewed the perioperative care of 61 anesthetics performed on eight
      patients with spinal muscular atrophy type 2 who received nusinersen over 30
      months in conjunction with nusinersen's phase 3 clinical trials. METHODS:
      Anesthesia was induced in all patients with sevoflurane, nitrous oxide, and
      oxygen (30%) via facemask. A peripheral intravenous line was placed after the
      loss of consciousness in all but three procedures. General anesthesia was
      maintained in 58 anesthetics with a propofol infusion at 250-300 MUg/kg/min,
      while the remainder was maintained with inhalational anesthetics. The airway was
      managed via facemask or nasal cannula in all but two procedures, in whom a
      laryngeal mask airway was placed. We analyzed patient demographics, duration of
      anesthesia and of postanesthesia care unit stay, discharge destination,
      preprocedure oxygen saturation (SaO2 ), postanesthesia care unit discharge oxygen
      saturation, and occurrence of unanticipated admission or postdischarge
      hospitalization. RESULTS: Eight American Society of Anesthesiologists physical
      status three patients (3 male: 5 female) with a median age of 4.1 (2.1-7.8) years
      and median weight of 13.2 (10-24.7) kg, underwent 61 anesthetics for nusinersen
      administration or sham procedure. There were no intraoperative anesthetic
      complications of unanticipated cardiovascular instability, major neurologic
      events, respiratory failure, or death. Anesthesiologists performed 83% of the
      procedures. CONCLUSION: Nusinersen has revolutionized the care of patients with
      spinal muscular atrophy type 2 and anesthesiologists will be involved in its
      administration. We found that routine anesthetic care was safe and effective.

PMID- 30284762
TI  - Design, Synthesis and Molecular Docking Studies of some Tetrahydropyrimidine
      Derivatives as Possible Fascin Inhibitors.
AB  - Eight derivatives of tetrahydropyrimidine scaffold were designed and prepared as
      hybrid compounds possessing the structural features of both Monastrol as an
      anticancer drug and Nifedipine as a Fascin blocking agents. All of the compounds
      were evaluated for their cytotoxic potency and the ability to inhibit 4T1 breast
      cancer cells migration. Then they were investigated in silico for their ability
      to inhibit the Fascin protein using molecular docking simulation. The most potent
      and the weakest compounds according to the in vitro cytotoxicity assay were 4d
      and 4a with IC50 values of 193.70 and 248.75 umol, respectively. The least
      cytotoxic compound (4a) was one of the strongest ones in binding to the Fascin
      binding site according to molecular docking results. 4a and 4e inhibited the 4T1
      cells migration better than other compounds. They were more potent than
      Nifedipine in inhibiting the migration process. In silico studies proved 4h as
      the most potent Fascin inhibitor in terms of DeltaGbind although it was not
      inhibiting migration. The controversy between the in vitro and in silico results
      may cancel the postulation of the involvement of the Fascin inhibition in the
      migration inhibition. However, the considerable anti-migratory effects of some of
      the synthesized compounds proved it reasonable to perform further in vivo
      experiments to introduce novel tumor metastasis inhibitors.

PMID- 30284763
TI  - Listening to the voice of patients with head and neck cancer: A systematic review
      and meta-synthesis.
AB  - The aim was to conduct a systematic review and a meta-synthesis of primary
      qualitative studies exploring experiences of head and neck cancer patients (HNC)
      undergoing radio and/or chemotherapy, in order to provide a better understanding
      of this phenomenon and supply new directions for care and clinical practice. Six
      databases were systematically searched, and 13 studies were included. The meta
      synthesis methodology was adopted to conceptualise the way in which patients
      lived their cancer journey and the impact of treatments on their daily life. Four
      themes embracing various aspects of HNC patients' experiences were identified:
      (a) self-body image and perceived quality of life; (b) experiences and treatment
      of symptoms; (c) cancer journey; and (d) the relationship with health
      professionals. The finding demonstrates the importance of acknowledging that
      treatment sequelae and patients' daily issues do not appear, develop and affect
      people's lives in isolation and should be considered and analysed as a whole
      within the social and cultural context of patients' lives. Further research is
      needed to explore the treatment experience of HNC patients throughout their
      cancer journey with a more holistic approach that involves health professionals,
      caregivers and other family members and peers in the community.

PMID- 30284764
TI  - One step up the ladder of prebiotic complexity: Formation of non-random linear
      polypeptides from binary systems of amino acids on silica.
AB  - We have evidenced the formation of linear oligopeptides with non-random sequences
      from mixtures of amino acids coadsorbed on silica and submitted to a simple
      thermal activation. The amino acid couples (Glutamic acid + Leucine) and
      (Aspartic acid + Valine) were deposited on a fumed silica and submitted to a
      single heating step at moderate temperature. The evolution of the systems was
      characterized by X-Ray Diffraction, InfraRed spectroscopy, Thermogravimetric
      Analysis, HPLC and Electrospray Ionization Mass Spectrometry (ESI-MS). The
      formation of amide bonds was evidenced in all systems studied. While the products
      of single amino acids activation on silica could be considered as evolutionary
      dead ends, (Glutamic acid + Leucine) and, at least to some extent, (Aspartic acid
      + Valine) gave rise to the high yield formation of linear peptides up to the
      hexamers. Oligopeptides of such length had not been observed before in surface
      polymerization scenarios (unless the amino acids had been deposited by chemical
      vapor deposition, which is not realistic prebiotically). Furthermore, not all
      possible amino acid sequences were present in the activation products, indicative
      of polymerization selectivity. These results are promising for origins of life
      studies since they suggest the emergence of non-random biopolymers in a simple
      prebiotic scenario.

PMID- 30284765
TI  - Isothiazolinone derivatives and allergic contact dermatitis: a review and update.
AB  - Allergic contact dermatitis (ACD) from isothiazolinones has frequently been
      described in the literature. Following an epidemic of sensitization to
      methylchloroisothiazolinone/ methylisothiazolinone (MCI/MI) in the 1980's, and
      more recently to MI, the Scientific Committee on Consumer Safety of the European
      Commission banned their use in leave-on products, whilst restricting that in
      rinse-off cosmetics. Despite a decreasing prevalence of allergic contact
      dermatitis from MCI/MI and MI, cases caused by occupational exposure and non
      cosmetic isothiazolinone sources are on the rise. Moreover, sensitization to
      newer and lesser known isothiazolinones has been reported. This paper reviews the
      epidemiology of contact allergy to different isothiazolinones, clinical
      presentation of isothiazolinone-induced allergic contact dermatitis, most
      relevant sensitization sources, and potential cross-reactions between
      isothiazolinone derivatives. It also provides an update on recent legislative
      measures. This article is protected by copyright. All rights reserved.

PMID- 30284766
TI  - Stereoselective Sensing of l- and d-Amino Acids: Development of a Fluorescence
      Array Based on Readily Available Chiral Phosphoric Acids.
AB  - The identification of structurally related analytes has become possible using
      sensor arrays, based on sets of cross-reactive chemosensors. This work reports
      the use of readily available chiral phosphoric acids for the array-based, chemo-
      and stereoselective sensing of l- and d-amino acids. Six bis- and trisphosphoric
      acids were used in combination with Ni2+ and Eu3+ , resulting in a set of twelve
      chiral fluorescent chemosensors. This sensor-array enables a correct
      classification of l-amino acids with 100 % accuracy, while the differentiation
      between l- and d-amino acids can be achieved with 94 % accuracy. In addition, the
      systematic analysis of sensor contributions has allowed the use of a reduced set
      of seven sensors for the classification of l-amino acids, thus drastically
      reducing the amount of necessary measurements.

PMID- 30284767
TI  - Interarm Blood Pressure Difference is Associated with Early Neurological
      Deterioration, Poor Short-Term Functional Outcome, and Mortality in
      Noncardioembolic Stroke Patients.
AB  - BACKGROUND AND PURPOSE: Interarm differences in the systolic and diastolic blood
      pressures (IASBD and IADBD, respectively) are found in various populations,
      including stroke patients, but their significance for stroke outcomes has rarely
      been reported. We aimed to determine the associations of IASBD and IADBD with
      early neurological deterioration (END), functional outcome, and mortality.
      METHODS: This study included 1,008 consecutive noncardioembolic cerebral
      infarction patients who were admitted within 24 hours of onset and had automatic
      measurements of blood pressures in the bilateral arms. END was assessed within 72
      hours of stroke onset according to predefined criteria. A poor functional outcome
      was defined as a score on the modified Rankin Scale >=3 at 3 months after the
      index stroke. All-cause mortality was also investigated during a median follow-up
      of 24 months. The absolute difference of blood pressure measurements in both arms
      were used to define IASBD and IADBD. RESULTS: END occurred in 15.3% (155/1,008)
      of the patients. A multivariate analysis including sex, age, and variables for
      which the p value was <0.1 in a univariate analysis revealed that IASBD >=10 mm
      Hg was significantly associated with END [odds ratio (OR)=1.75, 95% CI=1.02
      3.01]. IADBD >=10 mm Hg was also related to END (OR=3.11, 95% CI=1.61-5.99).
      Moreover, having both IASBD >=10 mm Hg and IADBD >=10 mm Hg was related to a poor
      functional outcome (OR=2.67, 95% CI=1.36-5.35) and mortality (hazard ratio=7.67,
      95% CI=3.76-12.83) even after adjusting for END. CONCLUSIONS: This study suggests
      that an interarm blood pressure difference of >=10 mm Hg could be a useful
      indicator for the risks of END, poor functional outcome, and mortality.

PMID- 30284769
TI  - Hashimoto Encephalopathy Mimicking Acute Ischemic Stroke: Perfusion-Weighted
      Magnetic Resonance Imaging.

PMID- 30284770
TI  - Cerebral Large-Vessel Vasculitis in Sjogren's Syndrome: Utility of High
      Resolution Magnetic Resonance Vessel Wall Imaging.

PMID- 30284768
TI  - Insufficient Sleep in Tension-Type Headache: A Population Study.
AB  - BACKGROUND AND PURPOSE: Sufficient sleep is an essential part of good health and
      well-being. Tension-type headache (TTH) is the most common type of primary
      headache and has negative impacts on the quality of life and work performance. We
      aimed to determinethe relationship between TTH and insufficient sleep in the
      general population. METHODS: This study used data from the Korean Headache Sleep
      Study, which was a population-based survey about headache and sleep among Korean
      adults. Insufficient sleep was defined when the discrepancy between sleep need
      and average sleep duration was at least 1 hour. RESULTS: Among the 2,695 included
      subjects, 570 (21.2%) and 727 (27.0%) were classified as having TTH and
      insufficient sleep, respectively. The prevalence of insufficient sleep was
      significantly higher among subjects with TTH than among those without headaches
      (28.8% vs. 20.4%). For subjects with TTH, the scores on a visual analogue scale
      (4.7+/-1.8 vs. 4.3+/-1.9, mean+/-SD) and the Headache Impact Test-6 (44.9+/-7.0
      vs. 43.6+/-6.1) were much higher in subjects with insufficient sleep than in
      those without insufficientsleep. Multivariable analyses revealed that insomnia
      [odds ratio (OR)=2.1], poor sleep quality (OR=1.7), and short sleep duration
      (OR=6.9) were significantly associated with insufficient sleep in subjects with
      TTH. CONCLUSIONS: Our findings suggest that insufficient sleep is prevalent among
      subjects with TTH and is linked to an exacerbation of TTH. Therefore, the proper
      evaluation and management of sleep may lead to the better management of TTH.

PMID- 30284771
TI  - A Novel Nonsense Mutation in Leucine-Rich, Glioma-Inactivated-1 Gene as the
      Underlying Cause of Familial Temporal Lobe Epilepsy.

PMID- 30284772
TI  - Effect of Levetiracetam Monotherapy on Liver Enzymes and Creatine Kinase
      Concentrations in Children with Epilepsy: A Prospective Study.

PMID- 30284773
TI  - A Novel Heterozygous ANO3 Mutation with Basal Ganglia Dysfunction in a Patient
      with Adult-Onset Isolated Segmental Dystonia.

PMID- 30284774
TI  - The Relationship between Anti-Myelin Oligodendrocyte Glycoprotein Antibody
      Associated Disease and the Rubella Virus.

PMID- 30284775
TI  - Mycotic Cerebral Aneurysms Secondary to Scedosporium Prolificans Infection in a
      Patient with Multiple Sclerosis.

PMID- 30284776
TI  - Decision tree analysis for factors associated with dental caries in school-aged
      children in Japan.
AB  - OBJECTIVE: Our study aimed to elucidate the interactive relationship between
      factors associated with dental caries in school children using decision tree
      analysis. RESEARCH DESIGN: Cross-sectional study Methods: Participants were
      recruited from public primary schools (9-12 years, 4th to 6th grade) and junior
      high schools (12-13 years, 1st grade) in Japan. A total of 1775 students (928
      boys and 847 girls) were analyzed. Questionnaire survey, oral examination, and
      saliva test were performed. Multiple logistic regression and decision tree
      analysis were performed. RESULTS: Multiple logistic regression showed an
      association between dental caries and toothpaste use, dental attendance and the
      presence of Streptococcus mutans. Decision tree analysis showed that students
      with non-regular dental attendance were at a significantly higher risk of dental
      caries at the late stage of primary school. At the early stage of primary school,
      high levels of Streptococcus mutans and male sex were factors associated with
      dental caries. In students with low levels of Streptococcus mutans, using
      toothpaste occasionally was associated with a high risk of dental caries.
      CONCLUSIONS: In early primary school years, S. mutans may be a useful screening
      and diagnostic tool for dental caries. In students with high levels of S. mutans,
      sex may be associated with dental caries. Furthermore, in students with low
      levels of S. mutans, regular use of toothpaste should be encouraged, and in late
      primary school years, regular dental attendance should be encouraged to prevent
      dental caries.

PMID- 30284777
TI  - Dentist's views on incorporating oral health collaborative practice into primary
      medical care in Ireland.
AB  - BACKGROUND: In order to address the burden of oral disease, the dental profession
      needs to engage in collaborative practice with medical professionals. The aim of
      this study was to explore dentists' views on incorporating oral health
      collaborative practice into primary medical care in Ireland. SETTING: Dublin
      Dental University Hospital, Ireland. PARTICIPANTS: Dentists with backgrounds in
      oral surgery, oral medicine, paediatric dentistry, special care dentistry,
      prosthodontics, primary care dentistry, hospital dentistry and public dental
      health. All participants were working in, or had worked in, Dublin Dental
      University Hospital for a minimum of six months full-time equivalent within the
      previous 5 years. METHODS: Semi-structured qualitative interviews were undertaken
      in five phases, transcribed verbatim and thematically analyzed. RESULTS: A total
      of 17 participants were recruited. After 14 interviews, no new themes were
      emerging and data saturation was achieved. Eleven codes were identified and
      organized into four themes; (i) the relative importance of oral health to
      systemic health, (ii) the role of dentistry in the overall health care team,
      (iii) oral health interprofessional education and training, (iv) opportunities
      for oral health collaborative practice. CONCLUSION: Dentists felt that the best
      way to achieve effective oral health collaborative practice with primary medical
      care would be to educate medical professionals on how to identify the significant
      risk factors for oral disease, how to promote oral health and how to facilitate
      access to primary dental care for their patients.

PMID- 30284778
TI  - Assessing and managing malnutrition in adults in hospital.
AB  - The term malnutrition refers to both undernutrition and overnutrition. In
      healthcare, it most often refers to undernutrition, in particular disease-related
      malnutrition, which can be a result or a cause of an illness. The reasons for
      malnutrition are multifactorial, and its consequences may include an increased
      risk of pressure ulcers, reduced mobility and psychological effects such as
      depression. It is essential that nurses prioritise the nutritional care of all
      patients and identify those at risk of malnutrition using accurate and reliable
      nutrition screening tools. If there is a risk of malnutrition, further assessment
      and nutrition action planning can reduce the risk to the patient and improve
      their nutritional status. This article discusses the effects of disease-related
      malnutrition and outlines the role of screening tools and assessment in
      identifying patients who are malnourished or at risk of becoming malnourished. It
      also describes the nursing care that should be provided to patients with disease
      related malnutrition, and emphasises the importance of using a multidisciplinary
      team approach involving speech and language therapists, dieticians, occupational
      therapists and physiotherapists.

PMID- 30284779
TI  - The Incentive Starting Line: Where to Start When Designing Your New Safety
      Incentive Program.
AB  - Incentives excel at motivating important behaviors. Incentives also motivate
      people to go above and beyond their job requirements.

PMID- 30284780
TI  - Beaconing Sheds Light on the Darkness of Gas Monitor Data.
AB  - How can you proactively fix a problem when you don't know where it occurred?

PMID- 30284781
TI  - When an Employee Says No.
AB  - Proper documentation is needed to protect your organization from liability when
      an employee refuses emergency medical care during work related and non-work
      related illness and injury.

PMID- 30284782
TI  - A Proposed Solution to the High Cost of Opioid Abuse.
AB  - Through collaboration, safety professionals and physical therapists can achieve
      optimal results with both prevention and post-injury management.

PMID- 30284783
TI  - What Should You Stop Doing to Improve Safety Performance and Culture?
AB  - Thinking we can always be better, and hazards and risks can always be reduced,
      should dominate thinking throughout an organization.

PMID- 30284784
TI  - 3 B's for Preventing Soft-Tissue Injuries.
AB  - The 3 B's are effective watchpoints for moving and working stronger, safer, and
      more in control.

PMID- 30284785
TI  - Latest Rule Boosts Our Food Safety Preparedness.
AB  - The registration of food facilities has long been considered a key component of
      food safety.

PMID- 30284786
TI  - On the Move.

PMID- 30284787
TI  - 12 Items to Prevent Winter Weather Incidents and Illnesses (and You May Already
      Have Most of Them).
AB  - Allowing time for workers to acclimate to working in cold weather and limiting
      the length of outdoor shifts help prevent cold-related injuries. The right types
      of protective clothing are also essential.

PMID- 30284788
TI  - 2015-2016 Construction Safety Highlights.
AB  - From OSHA's National Safety Stand-Down to bridge collapse investigations and
      trenching hazards, the construction industry can learn from mistakes in order to
      boost its safety performance.

PMID- 30284790
TI  - Counting Down to NSC 2016.
AB  - The pre-conference program identifies 10 technical sessions as "hot topics" for
      this year-and they look very promising.

PMID- 30284789
TI  - Temporary Electrical Power, Keeping it Safe!
AB  - If planned properly, many components that will be a part of the permanent and
      final installation could be a part of the overall temporary power for the
      project.

PMID- 30284791
TI  - Everyone is Out of the Building. Now What?
AB  - Be prepared to communicate. This is an element of response that is often
      overlooked and needs to be continually practiced.

PMID- 30284792
TI  - What Is Your Life-Saving Gas Monitor Trying to Tell You?
AB  - The bottom line is that, in a given day, a worker could be alerted to the same
      hazardous condition in many different ways, none of which clearly and efficiently
      tells the story of what's happening.

PMID- 30284793
TI  - What Should You Know When Purchasing a WBGT Instrument?
AB  - In 2014 alone, 2,630 workers suffered from heat illness and 18 died, according to
      the U.S. Department of Labor.

PMID- 30284794
TI  - BBS and Leadership Analytics: Using Your Big Data to Engage Your Team.
AB  - To assess their leadership engagement, safety professionals can poll their
      employees to determine the amount and the quality of BBS information
      disseminated.

PMID- 30284795
TI  - Understanding the ANSI Z358.1-2014 Standard for Plumbed and Portable Eyewash
      Stations.
AB  - The ANSI Z358.1-2014 standard serves as a benchmark within the United States and
      also internationally to help protect workers from eye injuries from caustic and
      corrosive substances.

PMID- 30284796
TI  - Characteristics of Effective Safety Culture Change Agents.
AB  - Often, employees who have been injured develop serious attitudes about safety and
      have great credibility when they speak about safety to others.

PMID- 30284797
TI  - Leading Expectations.
AB  - Positive expectations are definitely helpful-as long as they're in balance.

PMID- 30284798
TI  - In Praise of NSC's Moonshot.
AB  - I applaud the NSC's chief executive and the council for setting this ambitious
      goal and keeping it on the front burner at every opportunity.

PMID- 30284799
TI  - There Must Be Accountability for Those Who Don't Respond Appropriately.

PMID- 30284800
TI  - Enzalutamide in Castration-Resistant Prostate Cancer.

PMID- 30284801
TI  - Enzalutamide in Castration-Resistant Prostate Cancer.

PMID- 30284802
TI  - Azithromycin and Childhood Mortality in Africa.

PMID- 30284803
TI  - Azithromycin and Childhood Mortality in Africa.

PMID- 30284804
TI  - Azithromycin and Childhood Mortality in Africa.

PMID- 30284805
TI  - Repeated Intrinsic Self-Healing of Wider Cracks in Polymer via Dynamic Reversible
      Covalent Bonding Molecularly Combined with a Two-Way Shape Memory Effect.
AB  - To enable repeated intrinsic self-healing of wider cracks in polymers, a proof-of
      concept approach is verified in the present work. It operates through two-way
      shape memory effect (SME)-aided intrinsic self-healing. Accordingly, a reversible
      C-ON bond is introduced into the main chain of crosslinked polyurethane (PU)
      containing an elastomeric dispersed phase (styrene-butadiene-styrene block
      copolymer, SBS). The PU/SBS blend was developed by the authors recently, and
      proved to possess an external stress-free two-way SME after programming. As a
      result, the thermal retractility offered by the SME coupled with the reversible C
      ON bonds can be used for successive crack closure and remending based on
      synchronous fission/radical recombination of C-ON bonds. Moreover, multiwalled
      carbon nanotubes are incorporated to impart electrical conductivity to the
      insulating polymer. Repeated autonomic healing of wider cracks is thus achieved
      through narrowing of cracks followed by chemical rebonding under self-regulating
      Joule heating. No additional programming is needed after each healing event,
      which is superior to one-way SME-assisted self-healing. The outcomes set an
      example of integrating different stimuli-responsivities into single materials.

PMID- 30284806
TI  - Chronic Social Isolation Stress during Peri-Adolescence Alters Presynaptic
      Dopamine Terminal Dynamics via Augmentation in Accumbal Dopamine Availability.
AB  - Chronic peri-adolescent stress in humans increases risk to develop a substance
      use disorder during adulthood. Rats reared in social isolation during peri
      adolescence (aSI; 1 rat/cage) period show greater ethanol and cocaine intake
      compared to group housed (aGH; 4 rats/cage) rats. In addition, aSI rats have a
      heightened dopamine response in the nucleus accumbens (NAc) to rewarding and
      aversive stimuli. Furthermore, single pulse electrical stimulation in slices
      containing NAc core elicits greater dopamine release in aSI rats. Here, we
      further investigated dopamine release kinetics and machinery following aSI.
      Dopamine release, across a wide range of stimulation intensities and frequencies,
      was significantly greater in aSI rats. Interestingly, subthreshold intensity
      stimulations also resulted in measurable dopamine release in accumbal slices from
      aSI but not aGH rats. Extracellular [Ca2+] manipulations revealed augmented
      calcium sensitivity of dopamine release in aSI rats. The readily releasable pools
      of dopamine, examined by bath application of Ro-04-1284/000, a vesicular
      monoamine transporter 2 (VMAT2) inhibitor, were depleted faster in aGH rats.
      Western blot analysis of release machinery proteins (VMAT2, Synaptogyrin-3,
      Syntaxin-1, and Munc13-3) showed no difference between the two groups. Tyrosine
      hydroxylase (TH) protein expression levels, however, were elevated in aSI rats.
      The greater dopamine release could potentially be explained by higher levels of
      TH, the rate-limiting step for dopamine synthesis. This augmented responsivity of
      the dopamine system and heightened dopamine availability post-aSI may lead to an
      increased risk of addiction vulnerability.

PMID- 30284807
TI  - Design of Gold Hollow Nanorods with Controllable Aspect Ratio for Multimodal
      Imaging and Combined Chemo-Photothermal Therapy in the Second Near-Infrared
      Window.
AB  - Gold nanoparticles (AuNPs) exhibit great potential for biological applications
      due to their good biocompatibility and tunable localized surface plasmon
      resonance (LSPR) properties. Currently, although tuning the aspect ratio of a
      solid structure or designing a hollow structure has been performed to regulate
      the LSPR properties of AuNPs, the method of preparing hollow anisotropic AuNPs
      has rarely been reported. In this study, we designed gold hollow nanorods
      (AuHNRs) with controllable aspect ratios by a Se-doping Te nanorod-templated
      method with the assistance of l-cysteine. UV-vis-NIR spectra showed that AuHNRs
      with an aspect ratio of about 3 could have a LSPR peak in the second near
      infrared (NIR-II) window, which is only half of the value required by traditional
      Au nanorods. Moreover, AuHNRs are nontoxic and capable of loading drugs. In vivo
      experiment revealed that AuHNRs can be used as contrast agents in multimodal
      imaging, including photothermal imaging, photoacoustic imaging, and computed
      tomography imaging, as well as in chemo-photothermal combined therapy of tumor in
      the NIR-II window. Because light in the NIR-II window has remarkable advantages
      over that in the first near-infrared (NIR-I) window in biomedical applications,
      AuHNRs can be used as promising NIR-II-window-responsive multifunctional
      nanoagents.

PMID- 30284808
TI  - Long Cycle Life All-Solid-State Sodium Ion Battery.
AB  - All-solid-state sodium ion batteries (ASIBs) based on sulfide electrolytes are
      considered a promising candidate for large-scale energy storage. However, the
      limited cycle life of ASIBs largely restricts their practical application.
      Cycling-stable ASIBs can be achieved only if the designed cathode can
      simultaneously address challenges including insufficient interfacial contact,
      electrochemical and chemical instability between the electrode and electrolyte,
      and strain/stress during operation , rather than just addressing one or part of
      these challenges. Chevrel phase Mo6S8 has inherent high electronic conductivity
      and small volume change during sodiation/desodiation, and is chemically and
      electrochemically stable with the sulfide electrolyte, and therefore the only
      challenge of using Mo6S8 as the cathode for ASIBs is the insufficient contact
      between Mo6S8 and the solid electrolyte (SE). Herein, a thin layer of SE is
      coated on Mo6S8 using a solution method to achieve an intimate contact between
      Mo6S8 and the SE. Such a SE-coated Mo6S8 cathode enabled an ASIB with a high
      cycling performance (500 cycles), even much better than that of the liquid
      electrolyte batteries with the Mo6S8 cathode. This work provides valuable
      insights for developing long-cycle life ASIBs.

PMID- 30284809
TI  - Nanotechnology in Neuroscience Reveals Membrane Mobility Matters.
AB  - Quantum dots are nanometer-sized semiconductors that have size-tunable, narrow
      emission bands, high quantum yields, and are resistant to photobleaching. Ligand
      conjugated quantum dots enable the real time visualization of membrane proteins
      and have revealed that membrane diffusion dynamics are intrinsic to protein
      regulation, are susceptible to the level of membrane cholesterol, and are altered
      in genetic variants linked to disease, suggesting a mise en place approach to
      neuropsychopharmacology.

PMID- 30284810
TI  - Direct Evaluation of Live Uropathogenic Escherichia coli Adhesion and Efficiency
      of Antiadhesive Compounds Using a Simple Microarray Approach.
AB  - Many pathogens use host glycans as docking points for adhesion. Therefore, the
      use of compounds blocking carbohydrate-binding adhesins is a promising strategy
      for fighting infections. In this work, we describe a simple and rapid microarray
      approach for assessing the bacterial adhesion and efficiency of antiadhesive
      compounds targeting uropathogenic Escherichia coli UTI89, which displays mannose
      specific adhesin FimH at the tip of fimbriae. The approach consisted in direct
      detection of live fluorescently labeled bacteria bound to mannan printed onto
      microarray slides. The utility of the arrays for binding/inhibition assays was
      first validated by comparing array-derived results for the model mannose-binding
      lectin concanavalin A with data obtained by isothermal titration calorimetry.
      Growth phase-dependent binding of UTI89 to the arrays was observed, proving the
      usefulness of the setup for detecting differences in FimH expression.
      Importantly, bacteria labeling and binding assays entailed minimal manipulation,
      helping to preserve the integrity of fimbriae. The efficiency of three different
      dodecamannosylated fullerenes as FimH-targeted antiadhesives was next evaluated
      in competition assays. The results revealed a superior activity of the
      mannofullerenes (5- to 18-fold per mannose residue) over methyl alpha-d
      mannopyranoside. Moreover, differences in activity were detected for
      mannofullerenes differing in the structure/length of the spacer used for grafting
      mannose onto the fullerene core, further demonstrating the sensitivity of the
      assay. Overall, the approach combines straightforward and time-saving protocols
      for microarray preparation, bacteria labeling, and binding assays, and it can be
      easily tailored to other bacteria bearing carbohydrate-binding adhesins.

PMID- 30284811
TI  - Correction to Multiple Pathways to Bacterial Load Reduction by Stormwater Best
      Management Practices: Trade-Offs in Performance, Volume, and Treated Area.

PMID- 30284812
TI  - Salvaging the thermodynamic destabilization of interface histidine in
      transmembrane beta-barrels.
AB  - The ability of histidine to participate in a wide range of stabilizing polar
      interactions preferentially populates this residue in functionally important
      sites of proteins. Histidine possesses an amphiphilic and electrostatic nature
      essential for amino acids residing at membrane interfaces. However, the frequency
      of occurrence of histidine at membrane interfaces, particularly transmembrane
      beta-barrels, is lower than other aromatic residues. Here, we carry out
      comprehensive energetic measurements using equilibrium folding of the outer
      membrane enzyme PagP, to address the contribution of a C-terminal interface
      histidine on barrel stability. We show that placing histidine at the C-terminus
      universally destabilizes PagP by 4.0-8.0 kcal mol-1 irrespective of the
      neighboring residue. Spectroscopic and electrophoretic measurements indicate that
      the altered stability may arise from a loss in barrel compaction. Isoleucine,
      methionine, and valine salvage this destabilization marginally (in addition to
      tyrosine which shows an exceptionally high folding free energy value), when
      placed at the penultimate position, at the expense of an altered folding pathway.
      Double mutant cycle analysis indicates that the coupling energy between the
      terminal and penultimate residues in PagP-X160H161 increases when the intrinsic
      destabilization by the terminal H161 is high. Our observations that neighboring
      residues cannot salvage the energetic destabilization of histidine may explain
      why histidine is less abundant at membrane interfaces.

PMID- 30284813
TI  - Biodegradable Anisotropic Microparticles for Stepwise Cell Adhesion and
      Preparation of Janus Cell Microparticles.
AB  - The biomimetic anisotropic particles have different physicochemical properties on
      the opposite two sides, enabling diverse applications in emulsion, photonic
      display, and diagnosis. However, the traditional anisotropic particles have a
      very small size, ranging from submicrons to a few microns. The design and
      fabrication of anisotropic macron-sized particles with new structures and
      properties is still challenging. In this study, anisotropic polycaprolactone
      (PCL) microparticles well separated with each other were prepared by
      crystallization from the dilute PCL solution in a porous 3D gelatin template.
      They had fuzzy and smooth surfaces on each side, and a size as large as 70 MUm.
      The fuzzy surface of the particle adsorbed significantly larger amount of
      proteins, and was more cell-attractive regardless of the cell types. The
      particles showed stronger affinity toward fibroblasts over hepatocytes, which
      paved a new way for cell isolation merely based on the surface morphology. After
      a successive seeding process, Janus cell microparticles with fibroblasts and
      endothelial cells (ECs) on each side were designed and obtained by making use of
      the anisotropic surface morphology, which showed significant difference in EC
      functions in terms of prostacyclin (PGl2) secretion, demonstrating the unique and
      appealing functions of this type of anisotropic microspheres.

PMID- 30284814
TI  - Solid-State Nanopore Easy Chip Integration in a Cheap and Reusable Microfluidic
      Device for Ion Transport and Polymer Conformation Sensing.
AB  - Solid-state nanopores have a huge potential in upcoming societal challenging
      applications in biotechnologies, environment, health, and energy. Nowadays, these
      sensors are often used within bulky fluidic devices that can cause cross
      contaminations and risky nanopore chips manipulations, leading to a short
      experimental lifetime. We describe the easy, fast, and cheap innovative 3D
      printer-helped protocol to manufacture a microfluidic device permitting the
      reversible integration of a silicon based chip containing a single nanopore. We
      show the relevance of the shape of the obtained channels thanks to finite
      elements simulations. We use this device to thoroughly investigate the ionic
      transport through the solid-state nanopore as a function of applied voltage, salt
      nature, and concentration. Furthermore, its reliability is proved through the
      characterization of a polymer-based model of protein-urea interactions on the
      nanometric scale thanks to a hairy nanopore.

PMID- 30284815
TI  - Integration of Zn-Ag and Zn-Air Batteries: A Hybrid Battery with the Advantages
      of Both.
AB  - We report a hybrid battery that integrates a Zn-Ag battery and a Zn-air battery
      to utilize the unique advantages of both battery systems. In the positive
      electrode, Ag nanoparticles couple the discharge behaviors through the two
      distinct electrochemical systems by working as the active reactant and the
      effective catalyst in the Zn-Ag and Zn-air reactions, respectively. In the
      negative electrode, in situ grown Zn particles provide large surface areas and
      suppress the dendrite, enabling the long-term operating safety. The battery first
      exhibits two-step voltage plateaus of 1.85 and 1.53 V in the Zn-Ag reaction,
      after which a voltage plateau of 1.25 V is delivered in the Zn-air reaction, and
      the specific capacity reaches 800 mAh gZn-1. In addition, excellent reversibility
      and stability with maintaining high energy efficiency of 68% and a capacity
      retention of nearly 100% at 10 mA cm-2 are demonstrated through 100 cycles,
      outperforming both conventional Zn-air and Zn-Ag batteries. This work brings
      forth a conceptually novel high-performance battery, and more generally opens up
      new vistas for developing hybrid electrochemical systems by integrating the
      advantages from two distinct ones.

PMID- 30284816
TI  - Quadrupole Orbitrap Mass Spectrometer-Based Metabonomic Elucidation of Influences
      of Short-Term Di(2-ethylhexyl) phthalate Exposure on Cardiac Metabolism in Male
      Mice.
AB  - Di(2-ethylhexyl) phthalate (DEHP) can cause severe environmental pollution.
      Effects of DEHP on cardiac metabolism have been reported, but its mechanism(s) of
      action is not fully clear. Here, we used high-resolution mass spectrometry for
      metabonomics and molecular biological methods to identify the different
      endogenous metabolites affected by DEHP that might cause changes in cardiac
      metabolism in mice, map the network of metabolic pathways, and reveal (at the
      molecular level) how DEHP affects cardiac metabolism. The results showed that
      DEHP could inhibit the beta-oxidation of fatty acids and gluconeogenesis, promote
      glycolysis, and inhibit the tricarboxylic acid cycle in cardiomyocytes. DEHP
      caused mitochondrial dysfunction by inhibiting the synthesis and transport of
      fatty acids and, thus, inhibiting the synthesis and breakdown of adenosine
      triphosphate in mitochondria. Pathology revealed that DEHP could change the
      normal structures and functions of the heart and bodies of mice. DEHP can
      interfere with the physiological and metabolic function of the heart in mice by
      disrupting the endogenous metabolite and gene levels.

PMID- 30284817
TI  - Evaluation of Deuterium-Labeled JNJ38877605: Pharmacokinetic, Metabolic, and in
      Vivo Antitumor Profiles.
AB  - c-Met inhibitor JNJ38877605 has proven curative as an antitumor agent, while its
      clinical study was terminated due to renal toxicity. It was reported that the
      renal toxicity was caused by the poor solubility of its aldehyde oxidase (AO)
      metabolites. Therefore, blocking AO oxidation of JNJ38877605 might diminish the
      toxic metabolites and overcome the renal toxicity. Compound 3, the AO metabolic
      site deuterated JNJ38877605, was then synthesized as the target molecule. In
      vitro monkey liver S9 fraction incubation of 3 manifested that the renal toxic
      metabolite M2-2 was significantly reduced, which connoted that this deuteration
      has partly blocked AO oxidation. After po. nasal gavage to cynomolgus monkeys,
      compound 3 revealed decreased AO metabolites M2-2 and M3-2 in the plasma as well
      as 1.88-fold AUC and 1.56-fold Cmax compared with JNJ38877605, indicating that
      deuterium replacement significantly blocked AO metabolism in vivo. Besides,
      metabolic profiles of 3 were investigated by analysis of the plasma and the urine
      of the po. administrated cynomolgus monkeys. Moreover, after oral administration
      to the EBC-1 tumor-bearing nude mice, compound 3 exhibited a better antitumor
      efficacy than JNJ38877605. In conclusion, deuteration on the AO metabolic site of
      JNJ38877605 improved its AO metabolism, oral exposure, as well as in vivo
      antitumor efficacy.

PMID- 30284818
TI  - In Situ Measurement of the Size Distribution and Concentration of Insulating
      Particles by Electrochemical Collision on Hemispherical Ultramicroelectrodes.
AB  - One of the greatest limitations in electrochemical collision/nanoimpact methods
      is the inability to quantify the size of colliding species due to the uneven
      current distribution on a disk ultramicroelectrode UME (so-called edge effect).
      This phenomenon arises since radial diffusion is greater at the edge than the
      center of the active electrode surface. One method of solving this problem is
      fabrication of a hemispherical UME. We describe the fabrication of a
      hemispherical Hg UME on a disk UME by a solution-based electrochemical method,
      chronocoulometry. The use of hemispherical Hg UME to detect collisions of
      individual amine-functionalized polystyrene beads removes the "edge effect" and
      enables simultaneous measurements of the concentration and the size distribution
      of colloids in suspension. Using finite element simulations, we deduce a
      quantitative relation between the distribution of current step size and the size
      distribution of the bead. The frequency of collision measured for a given size of
      bead is then converted into a concentration (in mol/L) by a quantification of the
      relative contributions of migration and diffusion for each size of bead. Under
      our experimental conditions (low concentration of supporting electrolyte),
      migration dominates the flux of bead. The average size of polystyrene beads of
      0.5 and 1 MUm radius obtained by electrochemistry and scanning electron
      microscopy (SEM) differs by only -8% and -9%, respectively. The total
      concentration of polystyrene beads of 0.5 and 1 MUm radius obtained by
      electrochemistry is found in close agreement (<10% of error) with their nominal
      concentrations (25 and 100 fM).

PMID- 30284819
TI  - Screening and characterization of novel polyesterases from environmental
      metagenomes with high hydrolytic activity against synthetic polyesters.
AB  - The continuous growth of global plastics production, including polyesters, has
      resulted in increasing plastic pollution and subsequent negative environmental
      impacts. Therefore, enzyme-catalyzed depolymerization of synthetic polyesters as
      a plastics recycling approach has become a focus of research. In this study, we
      screened over 200 purified uncharacterized hydrolases from environmental
      metagenomes and sequenced microbial genomes and identified at least 10 proteins
      with high hydrolytic activity against synthetic polyesters. These include the
      metagenomic esterases MGS0156 and GEN0105, which hydrolyzed polylactic acid
      (PLA), polycaprolactone, as well as bis(benzoyloxyethyl)-terephthalate. With
      solid PLA as a substrate, both enzymes produced a mixture of lactic acid
      monomers, dimers, and higher oligomers as products. The crystal structure of
      MGS0156 was determined at 1.95 A resolution and revealed a modified alpha/beta
      hydrolase fold, with a lid domain and highly hydrophobic active site. Mutational
      studies of MGS0156 identified the residues critical for hydrolytic activity
      against both polyester and monoester substrates, with two-times higher
      polyesterase activity in the MGS0156 L169A mutant protein. Thus, our work
      identified novel, highly active polyesterases in environmental metagenomes and
      provided molecular insights into their activity, thereby augmenting our
      understanding of enzymatic polyester hydrolysis.

PMID- 30284820
TI  - Effects of HCO3- on Degradation of Toxic Contaminants of Emerging Concern by
      UV/NO3.
AB  - This study investigated the significant influence of HCO3- on the degradation of
      contaminants of emerging concern (CECs) during nitrate photolysis at 254 nm for
      water reuse applications. The second-order rate constants for the reactions
      between selected contaminants with carbonate radical (CO3*-) were determined at
      pH 8.8 and T = 20  degrees C: estrone ((5.3 +/- 1.1) * 108 M-1 s-1), bisphenol A
      ((2.8 +/- 0.2) * 108 M-1 s-1), 17alpha-ethynylestradiol ((1.6 +/- 0.3) * 108 M-1
      s-1), triclosan ((4.2 +/- 1.4) * 107 M-1 s-1), diclofenac ((2.7 +/- 0.7) * 107 M
      1 s-1), atrazine ((5.7 +/- 0.1) * 106 M-1 s-1), carbamazepine ((4.2 +/- 0.01) *
      106 M-1 s-1), and ibuprofen ((1.2 +/- 1.1) * 106 M-1 s-1). Contributions from UV,
      reactive nitrogen species (RNS), hydroxyl radical (*OH), and CO3*- to the CEC
      decomposition in UV/NO3- in the presence and absence of HCO3- were investigated.
      In addition, possible transformation products and degradation pathways of
      triclosan, diclofenac, bisphenol A, and estrone in UV/NO3-/HCO3- were proposed
      based on the mass (MS) and MS2 spectra. Significant reduction in the cytotoxicity
      of bisphenol A was observed after the treatment with UV/NO3-/HCO3-.

PMID- 30284821
TI  - Purification and Characterization of Naturally Occurring Post-Translationally
      Cleaved Ara h 6, an Allergen That Contributes Substantially to the Allergenic
      Potency of Peanut.
AB  - The 2S albumin Ara h 6 is one of the most important peanut allergens. A post
      translationally cleaved Ara h 6 (pAra h 6) was purified from Virginia type
      peanuts, and the cleavage site was mapped using high-resolution mass
      spectrometry. Compared to intact Ara h 6, pAra h 6 lacks a 5-amino acid stretch,
      resembling amino acids 43-47 (UniProt accession number Q647G9) in the
      nonstructured loop. Consequently, pAra h 6 consists of two chains: an N-terminal
      chain of approximately 5 kDa and a C-terminal chain of approximately 9 kDa, held
      together by disulfide bonds. Intermediate post-translationally cleaved products,
      in which this stretch is cleaved yet still attached to one of the subunits, are
      also present. The secondary structure and immunoglobulin E (IgE) binding of pAra
      h 6 resembles that of intact Ara h 6, indicating that the loss of the
      nonstructured loop is not critical for maintaining the protein structure.
      Commercially available monoclonal and polyclonal immunoglobulin G (IgG)
      antibodies directed to Ara h 6 react with both intact Ara h 6 and pAra h 6,
      suggesting that the involved epitopes are not located in the area that is post
      translationally cleaved. No differences between intact Ara h 6 and pAra h 6 in
      terms of IgE binding were found, suggesting that the area that is post
      translationally cleaved is not involved in IgE epitopes either. For all main
      cultivars Runner, Virginia, Valencia, and Spanish, intact Ara h 6 and pAra h 6
      occur in peanut at similar levels, indicating that pAra h 6 is a consistent and
      important contributor to the allergenic potency of peanut.

PMID- 30284822
TI  - Comparing the Descriptors for Investigating the Influence of Lattice Dynamics on
      Ionic Transport Using the Superionic Conductor Na3PS4- xSe x.
AB  - Recent work on superionic conductors has demonstrated the influence of lattice
      dynamics and the softness of the lattice on ionic transport. When examining
      either the changes in the acoustic phonon spectrum or the whole phonon density of
      states, both a decreasing activation barrier of migration and a decreasing
      entropy of migration have been observed, highlighting that the paradigm of "the
      softer the lattice, the better" does not always hold true. However, both
      approaches to monitor the changing lattice dynamics probe different frequency
      ranges of the phonon spectrum, and thus, it is unclear if they are complementary.
      In this work, we investigate the lattice dynamics of the superionic conductor
      Na3PS4- xSe x by probing the optical phonon modes and the acoustic phonon modes,
      as well as the phonon density of states via inelastic neutron scattering.
      Notably, Raman spectroscopy shows the evolution of multiple local symmetry
      reduced polyhedral species, which likely affect the local diffusion pathways.
      Meanwhile, density functional theory and the ionic transport data are used to
      compare the different approaches for assessing the lattice dynamics. This work
      shows that, while acoustic and inelastic methods may be used to experimentally
      assess the overall changing lattice stiffness, calculations of the average
      vibrational energies between the mobile ions and the anion framework are
      important to assess and computationally screen for ionic conductors.

PMID- 30284824
TI  - Copper-Catalyzed Intramolecular Annulation of Conjugated Enynones to Substituted
      1 H-Indenes and Mechanistic Studies.
AB  - Herein, a copper-catalyzed intramolecular cascade reaction of conjugated enynones
      to deliver substituted 1 H-indenes is reported. The inexpensive and less toxic
      copper salt served as the only catalyst in the transformation, affording the 3-(2
      furyl)-substituted 1 H-indenes in good to excellent yields under mild reaction
      conditions with broad functional group tolerance and making it highly appealing
      for synthetic organic chemistry. Notably, detailed DFT calculations have been
      carried out to elucidate that the reaction undergoes a copper-mediated 5- exo-dig
      cyclization of enynones to afford copper-(2-furyl)-carbene intermediate, followed
      by diene-carbene cyclization (one step but involving 6pi cyclization of Cu
      carbene and reductive elimination) and 1,5-hydrogen shift to provide the 1 H
      indenes.

PMID- 30284823
TI  - Photoactivation of MDM2 Inhibitors: Controlling Protein-Protein Interaction with
      Light.
AB  - Selectivity remains a major challenge in anticancer therapy, which potentially
      can be overcome by local activation of a cytotoxic drug. Such triggered
      activation can be obtained through modification of a drug with a photoremovable
      protecting group (PPG), and subsequent irradiation in the chosen place and time.
      Herein, the design, synthesis and biological evaluation is described of a
      photoactivatable MDM2 inhibitor, PPG-idasanutlin, which exerts no functional
      effect on cellular outgrowth, but allows for the selective, noninvasive
      activation of antitumor properties upon irradiation visible light, demonstrating
      activation with micrometer, single cell precision. The generality of this method
      has been demonstrated by growth inhibition of multiple cancer cell lines showing
      p53 stabilization and subsequent growth inhibition effects upon irradiation.
      Light activation to regulate protein-protein interactions between MDM2 and p53
      offers exciting opportunities to control a multitude of biological processes and
      has the potential to circumvent common selectivity issues in antitumor drug
      development.

PMID- 30284825
TI  - Tuning the Optoelectronic Properties of Stannoles by the Judicious Choice of the
      Organic Substituents.
AB  - Stannoles are organometallic rings in which the heteroatom is involved in a form
      of conjugation that is called sigma*-pi* conjugation. Only very little is known
      about how the substituents on the Sn atom or substituents on the stannole ring
      determine the optoelectronic properties of these heterocycles. In this work, this
      question has been studied experimentally and theoretically. Calculations of
      optimized equilibrium geometries, energy gaps between the highest occupied
      molecular orbitals (HOMOs) and lowest unoccupied molecular orbitals (LUMOs), and
      of the absorption spectra of a wide range of compounds were performed. The
      computational data showed that the substituents on the Sn atom influence the
      optoelectronic properties to a lower extent than the substituents in the 2 and 5
      positions of the ring. These substituents in the 2 and 5 positions of the
      stannole ring can also have a strong influence on the overall planarity of the
      structure, in which mesomeric effects can play a substantial role only if the
      structure is planar. Thus, only structures with a planar backbone are of interest
      in the context of tuning the optoelectronic properties. These were selected for
      the experimental studies. On the basis of this information, a series of six novel
      stannoles was synthesized by the formation of a zirconium intermediate and
      subsequent transmetalation to obtain the tin compound. The calculated electronic
      HOMO-LUMO energy gaps varied between 2.94 and 2.68 eV. The measured absorption
      maxima were located between 415 and 448 nm compared to theoretically calculated
      values ranging from 447 nm (2.77 eV) to 482 nm (2.57 eV). In addition to these
      optical measurements, cyclic voltammetry data could be obtained, which show two
      reversible oxidation processes for three of the six stannoles. With this study,
      it could be demonstrated how the judicious choice of the substituents can lead to
      large and predictable bathochromic shifts in the absorption spectra.

PMID- 30284826
TI  - Chromium-Catalyzed Regioselective Kumada Arylative Cross-Coupling of C(aryl)-O
      Bonds with a Traceless Activation Strategy.
AB  - We report here the chromium-catalyzed regioselective Kumada arylative cross
      coupling of C(aryl)-O bonds at ambient temperature. By using a simple and low
      cost chromium(II) chloride salt as a precatalyst, accompanied by a 2-pyridyl
      ligation, the catalytic cleavage and arylative coupling of C(aryl)-O bonds were
      achieved with a traceless activation strategy, overcoming the regioselectivity
      obstacle when several C-O bonds coexist in the Kumada coupling system.

PMID- 30284827
TI  - Total Synthesis of Complex Biosynthetic Late-Stage Intermediates and
      Bioconversion by a Tailoring Enzyme from Jerangolid Biosynthesis.
AB  - A highly convergent access to the late-stage biosynthetic intermediates
      projerangolid and jerangolid E is presented, and its utility is demonstrated by
      the synthesis of novel non-natural jerangolid derivatives. The key steps are
      fragment couplings by Julia-Kocienski olefination and olefin cross metathesis, as
      well as a stereoselective tetrahydropyran formation by intramolecular oxa-Michael
      addition. Bioconversion experiments with the tailoring O-methyltransferase JerF
      confirmed its proposed biosynthetic role and revealed relaxed substrate
      specificity of this enzyme as well as tolerance to organic cosolvents.

PMID- 30284828
TI  - A Synthesis of 3,4-Dihydroisoquinolin-1(2H)-one via the Rhodium-Catalyzed
      Alkylation of Aromatic Amides with N-Vinylphthalimide.
AB  - The alkylation of C-H bonds with N-vinylphthalimide by a rhodium-catalyzed
      reaction of aromatic amides containing an 8-aminoquinoline moiety as the
      directing group is reported. N-Vinylphthalimide functions as a 2-aminoethylating
      reagent. The resulting alkylated products can be converted into 3,4
      dihydroisoquinolin-1(2H)-one derivatives in a one-pot transformation. Deuterium
      labeling experiments suggest that the reaction proceeds through a carbene
      mechanism.

PMID- 30284829
TI  - Single-Ion Thermodynamics from First Principles: Calculation of the Absolute
      Hydration Free Energy and Single-Electrode Potential of Aqueous Li+ Using ab
      Initio Quantum Mechanical/Molecular Mechanical Molecular Dynamics Simulations.
AB  - A recently proposed thermodynamic integration (TI) approach formulated in the
      framework of quantum mechanical/molecular mechanical molecular dynamics (QM/MM
      MD) simulations is applied to study the structure, dynamics, and absolute
      intrinsic hydration free energy Deltas GM+,wat? of the Li+ ion at a correlated ab
      initio level of theory. Based on the results, standard values (298.15 K, ideal
      gas at 1 bar, ideal solute at 1 molal) for the absolute intrinsic hydration free
      energy [Formula: see text] of the proton, the surface electric potential jump
      chiwat? upon entering bulk water, and the absolute single-electrode potential
      [Formula: see text] of the reference hydrogen electrode are calculated to be 
      1099.9 +/- 4.2 kJ.mol-1, 0.13 +/- 0.08 V, and 4.28 +/- 0.04 V, respectively, in
      excellent agreement with the standard values recommended by Hunenberger and Reif
      on the basis of an extensive evaluation of the available experimental data (-1100
      +/- 5 kJ.mol-1, 0.13 +/- 0.10 V, and 4.28 +/- 0.13 V). The simulation results for
      Li+ are also compared to those for Na+ and K+ from a previous study in terms of
      relative hydration free energies DeltaDeltas GM+,wat? and relative electrode
      potentials [Formula: see text]. The calculated values are found to agree
      extremely well with the experimental differences in standard conventional
      hydration free energies DeltaDeltas GM+,wat* and redox potentials [Formula: see
      text]. The level of agreement between simulation and experiment, which is
      quantitative within error bars, underlines the substantial accuracy improvement
      achieved by applying a highly demanding QM/MM approach at the resolution-of
      identity second-order Moller-Plesset perturbation (RIMP2) level over calculations
      relying on purely molecular mechanical or density functional theory (DFT)
      descriptions. A detailed analysis of the structural and dynamical properties of
      the Li+ hydrate indicates that a correct description of the solvation structure
      and dynamics is achieved as well at this level of theory. Consideration of the
      QM/MM potential-energy components also shows that the partitioning into QM and MM
      zones does not induce any significant energetic artifact for the system
      considered.

PMID- 30284830
TI  - Atmospheric Fate of Criegee Intermediate Formed During Ozonolysis of Styrene in
      the Presence of H2O and NH3: The Crucial Role of Stereochemistry.
AB  - A gas-phase mechanistic investigation of the unimolecular, water/ammonia-assisted
      decomposition reactions of the alpha-hydroxy hydroperoxides (HPs) and
      hydroperoxide arylamines (a-HPs) produced during the styrene ozonolysis has been
      carried out theoretically in the present article. The instrumental role of
      stereochemistry in controlling the outcome of individual reactions has been
      discussed. Thermodynamic parameters (Delta G298K, Delta H298K, Delta E0K)
      associated with individual reactions have also been computed. The rate constants
      estimated for individual reactions using conventional transition state theory
      (TST) combined with statistical mechanics provide a comprehensive understanding
      of the reaction mechanism and also elucidate the atmospheric fate of Criegee
      intermediates. Considering the feasibility of reactions from thermodynamic and
      kinetic points of view, while aldehyde (PhCHO) formation pathway originating from
      bimolecular decomposition of HP is found to be kinetically favored, benzoic acid
      formation pathway remains favored thermodynamically. A similar consideration for
      the bimolecular reactions of a-HP reveals the phenylmethanimine formation pathway
      to be kinetically favored, while the benzamide formation pathway is favored
      thermodynamically. Our findings appear to be in excellent agreement with the
      experimental observations.

PMID- 30284831
TI  - Tracking DNA Synthesis with Single-Molecule Strand Displacement.
AB  - We have previously shown that double-stranded DNA labeled with a periodic series
      of fluorescent dyes can be used to track a single helicase. Here we demonstrate
      how this technique can be adapted to follow processive DNA synthesis. By
      monitoring strand displacement, we track the motion of a single phi29 DNA
      polymerase without labeling or altering the enzyme or the template strand, and
      without applying any force. We observe a wide range of speeds, with the highest
      exceeding by several times those observed in earlier in vitro single-molecule
      experiments. Because this method enables repeated observations of the same
      polymerase traversing identical segments of DNA, it should prove useful for
      determining the effects of sequence on DNA replication and transcription. In
      addition, future measurements of this type may allow us to examine in detail the
      interactions of individual DNA polymerases with other components of the
      replisome.

PMID- 30284832
TI  - Fast Construction of 1,3-Benzothiazepines by Direct Intramolecular
      Dehydrogenative C-S Bond Formation of Thioamides under Metal-Free Conditions.
AB  - The first general protocol for the synthesis of 1,3-benzothiazepine derivatives
      was established. With the aid of bench-stable hypervalent iodine promoter fluoro
      HTIB, these seven-membered heterocycles can be rapidly synthesized from readily
      available thioamides under air atmosphere and metal-free conditions. The
      transformation can be completed within 1 min at room temperature and features a
      broad substrate scope.

PMID- 30284833
TI  - Desulfonylation-Initiated Distal Alkenyl Migration in Copper-Catalyzed
      Alkenylation of Unactivated Alkenes.
AB  - A novel and efficient protocol for desulfonylation-initiated distal alkenyl
      migration and its application to the elusive alkenylation of unactivated alkenes
      have been presented. This radical cascade process has successfully achieved the
      vicinal difluoroalkylalkenylation of unactivated alkenes with excellent chemo-,
      regio-, and stereoselectivity in high efficiency under mild conditions. The
      reactions afford previously unknown 3,3-difluoro-5-styrylpiperidin-2-one
      derivatives or beta-styryl-gamma-difluoroalkyl amines bearing a quaternary
      stereocenter. This is the first report of difunctionalization of unactivated
      alkenes through desulfonylation-initiated distal alkenyl migration.

PMID- 30284834
TI  - Conformationally Unambiguous Spin Label for Exploring the Binding Site Topology
      of Multivalent Systems.
AB  - Multivalent carbohydrate-lectin interactions are a key concept in biological
      processes mediating, for example, signaling and adhesion. Binding affinities of
      multivalent ligands often increase by orders of magnitude compared to a
      monovalent binding situation. Thus, the design of multivalent ligands as potent
      inhibitors is a highly active field of research, where knowledge about the
      binding site topology is crucial. Here, we report a general strategy for precise
      distance measurements between the binding sites of multivalent target proteins
      using monovalent ligands. We designed and synthesized Monovalent,
      conformationally Unambiguously Spin-labeled LIgands (MUeSLI). Distances between
      the binding sites of the multivalent model lectin wheat germ agglutinin in
      complex with a GlcNAc-derived MUeSLI were determined using pulsed electron
      paramagnetic resonance spectroscopy. This approach is an efficient method for
      exploring multivalent systems with monovalent ligands, and it is readily
      transferable to other target proteins, allowing the targeted design of
      multivalent ligands without structural information available.

PMID- 30284836
TI  - One-Pot Total Synthesis of Evodiamine and Its Analogues through a Continuous
      Biscyclization Reaction.
AB  - The one-pot total synthesis of evodiamine and its analogues is achieved using a
      three-component reaction. Through continuous biscyclization, various readily
      available substrates with good functional group tolerance were easily
      incorporated into biologically active quinazolinocarboline backbones. The use of
      triethoxymethane as a cosolvent was crucial for this quick and straightforward
      transformation.

PMID- 30284837
TI  - Cobalt-Catalyzed Direct C-H Thiolation of Aromatic Amides with Disulfides:
      Application to the Synthesis of Quetiapine.
AB  - A direct C(sp2)-H thiolation of aromatic amides with disulfides was developed.
      The coupling reaction proceeds between the thioether radical and cobaltacycle
      intermediate. This method exhibits a relatively broad substrate scope and high
      functional group compatibility. A mechanistic study indicates that the cobalt(IV)
      intermediate is probably formed during the course of the reaction. The thiolation
      product can be transformed to Quetiapine, which is an atypical antipsychotic
      agent approved for the treatment of schizophrenia and bipolar disorder.

PMID- 30284835
TI  - Quasi-Resonance Signal Amplification by Reversible Exchange.
AB  - Here we present the feasibility of NMR signal amplification by reversible
      exchange (SABRE) using radio frequency irradiation at low magnetic field (0.05 T)
      in the regime where the chemical shifts of free and catalyst-bound species are
      similar. In SABRE, the 15N-containing substrate and parahydrogen perform
      simultaneous chemical exchange on an iridium hexacoordinate complex. A shaped
      spin-lock induced crossing (SLIC) radio frequency pulse sequence followed by a
      delay is applied at quasi-resonance (QUASR) conditions of 15N spins of a 15N
      enriched substrate. As a result of this pulse sequence application, 15N z
      magnetization is created from the spin order of parahydrogen-derived
      hyperpolarized hydrides. The repetition of the pulse sequence block consisting of
      a shaped radio frequency pulse and the delay leads to the buildup of 15N
      magnetization. The modulation of this effect by the irradiation frequency, pulse
      duration and amplitude, delay duration, and number of pumping cycles was
      demonstrated. Pyridine-15N, acetonitrile-15N, and metronidazole-15N2-13C2
      substrates were studied representing three classes of compounds (five- and six
      membered heterocycles and nitrile), showing the wide applicability of the
      technique. Metronidazole-15N2-13C2 is an FDA-approved antibiotic that can be
      injected in large quantities, promising noninvasive and accurate hypoxia sensing.
      The 15N hyperpolarization levels attained with QUASR-SABRE on metronidazole-15N2
      13C2 were more than 2-fold greater than those with SABRE-SHEATH (SABRE in shield
      enables alignment transfer to heteronuclei), demonstrating that QUASR-SABRE can
      deliver significantly more efficient means of SABRE hyperpolarization.

PMID- 30284838
TI  - Pd-Catalyzed Alkylation of (Iso)quinolines and Arenes: 2-Acylpyridine Compounds
      as Alkylation Reagents.
AB  - The first Pd-catalyzed alkylation of (iso)quinolines and arenes is reported. The
      readily available and bench-stable 2-acylpyridine compounds were used as an
      alkylation reagent to form the structurally versatile alkylated (iso)quinolines
      and arenes. The method affords a convenient pathway for the introduction of alkyl
      groups into organic molecules.

PMID- 30284839
TI  - Site-Specific Oxidative C-H Chalcogenation of (Hetero)Aryl-Fused Cyclic Amines
      Enabled by Nanocobalt Oxides.
AB  - By employing reusable nanocobalt oxides as the catalysts, a site-specific
      oxidative C-H chalcogenation of (hetero)aryl-fused cyclic amines with various
      thiols and diselenides is presented for the first time. The reaction proceeds
      selectively at the sites of the (hetero)aryl rings para to the N atom, and
      enables access to a wide array of chalcogenyl N-heteroarenes. The merits of the
      transformation involve high step- and atom-efficiency, excellent substrate and
      functional compatibility, operational simplicity, and the use of a naturally
      abundant Co/O2 system. The present work has offered a fundamental basis for the
      selective synthesis of functional N-heteroarenes from readily available
      feedstocks.

PMID- 30284840
TI  - Recycling Catalyst as Reactant: A Sustainable Strategy To Improve Atom Efficiency
      of Organocatalytic Tandem Reactions.
AB  - A sustainable strategy by internally recycling an organocatalyst as a reactant in
      a downstream reaction to improve the atom efficiency of organocatalytic tandem
      reactions is described. Specifically, a one-pot tandem Cloke-Wilson/Boulton
      Katritzky reaction of cyclopropylketones with a hydroxylamine has been developed
      for the synthesis of fully substituted isoxazoles, in which the hydroxylamine
      serves as both an upstream catalyst and a downstream reactant.

PMID- 30284841
TI  - Correction to Total Synthesis of Pleofugin A, a Potent Inositol
      Phosphorylceramide Synthase Inhibitor.

PMID- 30284842
TI  - N-Methyl- N-phenylvinylsulfonamides for Cysteine-Selective Conjugation.
AB  - Use of N-methyl- N-phenylvinylsulfonamides to perform chemoselective modification
      of cysteine-containing peptides and proteins is reported. Probes linked to the
      drug were applicable to prepare antibody-drug conjugates (ADCs). The drug
      antibody ratio for ADCs was controlled by rationally tuning the electron
      deficiency and linker hydrophilicity of the probes.

PMID- 30284843
TI  - Examining cognitive functioning of adult acute psychiatric inpatients through a
      brief screening assessment.
AB  - OBJECTIVE: Psychiatric inpatients present with multiple difficulties, including
      comorbid diagnoses, social problems, trauma, and high levels of psychiatric
      medication use. All of these factors have been associated with poorer cognitive
      functioning, which is rarely assessed. The aim of this study was to examine the
      acceptability of a brief cognitive screening assessment, and identify the
      cognitive and psychological profile of current psychiatric inpatients. METHOD: A
      cross-sectional design was adopted. Participants (N = 75) were administered brief
      measures of cognitive functioning, the Montreal Cognitive Assessment (MoCA;
      Nasreddine et al., 2005), and psychological global distress, Clinical Outcomes of
      Routine Evaluation-Outcome Measure, (CORE-OM; Evans et al., 2002) within the
      first 4 weeks of their hospital admissions. RESULTS: The MoCA was identified as
      acceptable for the inpatient environment. Most of the participants (79%) met the
      cut-off for mild cognitive impairment. No significant differences were found
      across diagnoses in regard to cognitive functioning, but participants with
      diagnoses of personality disorder experienced the most psychological global
      distress. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Acute psychiatric inpatient
      wards should consider mild cognitive impairments when assessing and treating
      people with serious mental illness and make appropriate adaptations to their
      care. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284844
TI  - The consequences of self- and other-focused emotional intelligence: Not all
      sunshine and roses.
AB  - Emotional intelligence (EI) contributes to good performance and well-being in
      jobs that involve frequent interpersonal contact. However, as EI is composed of
      self- and other-focused dimensions, it remains unclear which dimensions are
      responsible for better performance and well-being. We hypothesized that other
      focused EI dimensions in particular relate to task performance, whereas self
      focused EI dimensions relate to employees' subjective stress and physiological
      responses to emotional job demands. We asked Dutch secretaries (N = 110) to
      professionally respond to five emotionally demanding work-related phone calls.
      The secretaries' skin conductance levels were recorded during the calls, and the
      secretaries had to indicate their stress levels after each call. Two independent
      raters coded the secretaries' effectiveness and the number of emotion regulation
      attempts during the phone calls. The results showed that other-focused emotion
      regulation was positively related to only one of the task performance indicators
      during three phone calls. In line with the hypotheses, self-focused emotion
      appraisal was negatively related to the secretaries' subjective stress levels
      after all the phone calls. Self-focused emotion regulation was positively related
      to the secretaries' skin conductance levels during all but one of the phone
      calls. This outcome suggests that self-focused EI dimensions decrease the
      subjective experience of stress but are accompanied by physiological costs,
      whereas other-focused emotion regulation may be positively but weakly related to
      task performance in emotionally demanding contexts. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 30284845
TI  - Prevention through job design: Identifying high-risk job characteristics
      associated with workplace bullying.
AB  - Work environment hypothesis, a predominant theoretical framework in workplace
      bullying literature, postulates that job characteristics may trigger workplace
      bullying. Yet, these characteristics are often assessed by employees based on
      their experience of the job. This study aims to assess how job characteristics,
      independently assessed via Occupational Information Network (O*NET), are related
      to perceived job characteristics reported by employees, which, in turn, are
      associated with self-reported workplace bullying. Multilevel mediation analyses
      from 3,829 employees in 209 occupations confirmed that employees, whose work
      schedules are more irregular and whose work involves a higher level of
      conflictual contact (as assessed by O*NET), report experiencing higher job
      demands, which are associated with higher exposure to bullying. Moreover,
      employees working in jobs structured to allow for more discretion in decision
      making (as assessed by O*NET) report experiencing more job autonomy and are less
      likely to experience bullying. The results offer some clues as to how the way in
      which a job is structured is related to how that job is perceived, which in turn
      is associated with exposure to bullying. Our findings also suggest that a job
      design perspective to redesign certain job characteristics may offer an
      additional viable approach to prevent workplace bullying. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 30284846
TI  - Testing intersectionality of race/ethnicity * gender in a social-cognitive career
      theory model with science identity.
AB  - Using social-cognitive career theory, we identified the experiential sources of
      learning that contribute to research self-efficacy beliefs, outcome expectations,
      and science identity for culturally diverse undergraduate students in science,
      technology, engineering, and math (i.e., STEM) majors. We examined group
      differences by race/ethnicity and gender to investigate potential cultural
      variations in a model to explain students' research career intentions. Using a
      sample of 688 undergraduate students, we ran a series of path models testing the
      relationships between the experiential sources, research self-efficacy beliefs,
      outcome expectations, and science identity to research career intentions.
      Findings were largely consistent with our hypotheses in that research self
      efficacy and outcome expectancies were directly and positively associated with
      research career intentions and the associations of the experiential sources to
      intentions were mediated via self-efficacy. Science identity contributed
      significant though modest variance to research career intentions indirectly via
      its positive association with outcome expectations. Science identity also
      partially mediated the efficacy-outcome expectancies path. The experiential
      sources of learning were associated in expected directions to research self
      efficacy with 3 of the sources emerging as significantly correlated with science
      identity. An unexpected direct relationship from vicarious learning to intentions
      was observed. In testing for group differences by race/ethnicity and gender in
      subsamples of Black/African American and Latino/a students, we found that the
      hypothesized model incorporating science identity was supported, and most paths
      did not vary significantly across four Race/Ethnicity * Gender groups, except for
      3 paths. Research and practice implications of the findings for supporting
      research career intentions of culturally diverse undergraduate students are
      discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284847
TI  - The development and evaluation of a brief form of the Normative Male Alexithymia
      Scale (NMAS-BF).
AB  - The current study extended prior work on the Normative Male Alexithymia Scale
      (NMAS), a unidimensional measure of some men's limitations in expressing emotion
      that results from gender-based socialization informed by the masculine norm of
      restrictive emotionality (RE). Data (N = 505 men) were from Amazon Mechanical
      Turk participants. First, dimensionality was reassessed using exploratory factor
      analysis, which supported the unidimensional structure. Second, based on these
      results, three 6-item models of the NMAS-Brief Form (NMAS-BF) were developed,
      based on classical test theory (CTT), CTT optimized to avoid item redundancy, and
      item response theory (IRT). Third, the relative fits of these versions were
      assessed using confirmatory factor analysis on a separate part of the sample,
      finding that the IRT version was the best fitting model. Fourth, evidence for
      reliability for the NMAS-BF items (alpha = .80) and validity was found.
      Convergent evidence for validity was supported by a significant, moderate,
      positive correlation between the latent constructs of the NMAS-BF and Toronto
      Alexithymia Scale-20 (TAS-20), which measures clinical alexithymia. Concurrent
      evidence for validity of the latent factor of the NMAS-BF was assessed in a
      structural regression model which found that the NMAS-BF uniquely predicted RE
      scores when TAS-20 scores were included in the model. Finally, incremental
      evidence for validity was examined using hierarchical multiple regression,
      finding that NMAS-BF scores significantly predicted variance in RE scores above
      and beyond that predicted by TAS-20 scores. The results are discussed in relation
      to prior literature, future research directions, applications to counseling
      practice, and limitations. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30284848
TI  - Current status of forensic lie detection with the comparison question technique:
      An update of the 2003 National Academy of Sciences report on polygraph testing.
AB  - Fifteen years have elapsed since a report was released by the National Academy of
      Sciences (NAS) on the scientific status of polygraph testing. The NAS report
      concluded that the scientific basis of the comparison question technique (CQT)
      was weak, the extant research was of low quality, the polygraph profession's
      claims for the high accuracy of the CQT were unfounded, and, although the CQT has
      greater than chance accuracy, its error rate is unknown. Polygraph proponents
      argue that current research indicates that the CQT has 90% or better accuracy,
      the National Research Council of the National Academy of Sciences' (2003)
      analysis supports this accuracy claim, and the CQT qualifies as legally
      admissible scientific evidence. We review the scientific literature that has
      appeared since the appearance of the NAS publication, including a new method for
      estimating polygraph accuracy. We show that the NAS report has been
      misrepresented and misinterpreted by those who support use of the CQT in forensic
      settings. We conclude that the quality of research has changed little in the
      years elapsing since the release of the NAS report, and that the report's
      landmark conclusions still stand. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30284849
TI  - Police tactics and guilt status uniquely influence suspects' physiologic
      reactivity and resistance to confess.
AB  - Research has identified numerous factors that influence suspects during police
      interrogations. However, the dynamics between individuals' physiologic reactivity
      and their confession decision making is in its infancy. This research sought to
      advance the interrogation literature by examining the relationships among
      different interrogation tactics, suspects' resistance to confess, and their
      physiologic reactivity during a mock interrogation. After manipulating innocence
      and guilt, participants (N = 154) were accused and interrogated using either a
      minimization or false evidence tactic. Participants' physiologic reactivity was
      operationalized using their systolic blood pressure, and confession resistance
      was quantified as the number of times participants refused to confess. Results
      demonstrated that participants exhibited more physiologic reactivity after being
      confronted with false evidence ploys than minimization. Furthermore, innocent
      participants resisted confessing more than guilty participants, but innocents
      confronted with false evidence resisted confessing to a greater extent than
      innocents confronted with minimization. Moreover, a moderated-mediation analysis
      indicated that although innocents resisted confessing more when confronted with
      false evidence than those confronted with minimization, these innocents sustained
      a significantly higher level of physiologic reactivity. The results of the
      conditional indirect relationship suggest that innocents who are confronted with
      false evidence may resist the most but at a cost-their greater resistance may
      exhaust them and undermine subsequent decision making. These results offer
      support for reforms aimed at reducing the length of interrogations and the use of
      interrogation tactics that unnecessarily increase false confession rates.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284850
TI  - Perceived discrimination and well-being among unauthorized Hispanic immigrants:
      The moderating role of ethnic/racial group identity centrality.
AB  - OBJECTIVES: We investigated the association between perceived ethnic
      discrimination with psychological well-being and life satisfaction among a
      community sample of unauthorized Hispanic immigrants in the United States. We
      also assessed whether ethnic/racial group identity centrality moderated this
      relationship. METHOD: A community sample of self-reported unauthorized Hispanics
      (N = 140) completed questionnaires assessing perceived ethnic discrimination,
      ethnic/racial group identity centrality, psychological well-being, and life
      satisfaction. RESULTS: Discrimination negatively predicted psychological well
      being and life satisfaction, and ethnic/racial group identity centrality
      moderated these relationships. High ethnic/racial group identity centrality
      reduced the association of discrimination with psychological well-being and life
      satisfaction. Ethnic/racial identity centrality lent psychological protection for
      those who reported higher levels of discrimination. CONCLUSION: Ethnic
      discrimination is a salient stressor for unauthorized Hispanic immigrants. Yet
      high ethnic/racial group identity centrality may protect these individuals from
      the negative effects of discrimination by providing a sense of belonging,
      acceptance, and social support in the face of rejection. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 30284851
TI  - Ethnic-racial socialization in Latino families: The influence of mothers'
      socialization practices on adolescent private regard, familism, and perceived
      ethnic-racial discrimination.
AB  - OBJECTIVES: Cultural value endorsement and ethnic-racial identity promote
      Latino/a adolescent positive adaptation and mitigate the negative impacts of
      perceived ethnic-racial discrimination. This study explored the intergenerational
      process of how adolescents develop these cultural characteristics in concert with
      their experiences of discrimination, focusing on the role of youth-reported
      maternal ethnic-racial socialization processes. METHOD: Participants included 175
      Latino/a adolescent-mother dyads recruited from the 7th and 8th grades in an
      understudied emerging immigrant destination. We tested the effects of maternal
      cultural characteristics (i.e., familism, private regard, and perceived
      discrimination) on the same adolescent outcomes through youth-reported maternal
      ethnic-racial socialization practices (i.e., cultural socialization, preparation
      for bias, promotion of mistrust, and familism socialization, a novel construct
      introduced in this study). RESULTS: Three significant indirect pathways were
      identified. Higher maternal private regard was associated with both higher youth
      familism and higher youth private regard through greater youth-reported familism
      socialization, and higher maternal private regard was associated with more
      perceived youth discrimination through greater youth-reported preparation for
      bias. CONCLUSION: Our results highlight maternal private regard as particularly
      important for understanding how youth perceptions of socialization processes
      encourage the development of adolescent cultural characteristics and the benefit
      of using specific assessment tools, such as a familism socialization measure, to
      identify how ethnic-racial socialization processes serve as intergenerational
      links. Directions for future research and implications for intervention are
      discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284852
TI  - The effects of social power and apology on victims' posttransgression responses.
AB  - The purpose of this research was to test how, why, and when social power
      influences victims' revenge seeking, grudge holding, and forgiveness. Based on
      Keltner, Gruenfeld, and Anderson's (2003) power approach theory and McCullough,
      Kurzban, and Tabak's (2013) theorizing about revenge and forgiveness systems, we
      tested (a) the associations between victims' social power and revenge, grudge,
      and forgiveness; (b) the mediational role of approach/inhibition motivation in
      explaining why the associations exist; and (c) the moderating role of whether the
      transgressor apologizes or not in explaining the associations. Five studies (Ns =
      279, 181, 154, 131, and 81) that varied in sample (undergraduate, community),
      research method (nonexperimental, experimental), context (laboratory, online),
      measures (self-reported, behavioral), and statistical method (regression, ANOVA),
      supported our predictions and the systematic generalizability of the effects.
      Applied implications are discussed. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30284853
TI  - Conjoint differences in inhibitory control and processing speed in childhood to
      older adult cohorts: Discriminant functions from a Go/No-Go task.
AB  - To investigate differences in inhibitory control and processing speed over the
      life span, participants in 7- to 8-, 10- to 11-, 12- to 15-, 18- to 25-, and 54-
      to 80-year-old age cohorts completed a Go/No-Go task requiring varying levels of
      semantic categorization. Discriminant function analysis of correct rejection
      rates (CRRs), hit rates (HRs), and reaction times (RTs) revealed a function on
      which CRR loaded positively and RT loaded negatively, across categorization
      levels. Scores increased from youngest to the younger adult cohort and decreased
      for the older adult cohort. On a second function, CRR and RT loaded positively
      and HR loaded negatively across categorization levels. Scores were highest for
      the older adult cohort and higher for the youngest cohort than for the younger
      adult cohort. The results suggest change along 2 dimensions might underlie
      cognitive development: (a) combined increased inhibitory control and processing
      speed and (b) combined increased speed and decreased biased responding for better
      inhibitory control. In addition, 2 dimensions might underlie senescence: (a)
      combined decreased inhibitory control and processing speed and (b) combined
      decreased speed and increased biased responding for better inhibitory control.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284854
TI  - Adult age differences in the benefit of syntactic and semantic constraints for
      sentence processing.
AB  - Verbal working memory-intensive sentence processing declines with age. This might
      reflect older adults' difficulties with reducing the memory load by grouping
      single words into multiword chunks. Here we used a serial order task emphasizing
      syntactic and semantic relations. We evaluated the extent to which older compared
      with younger adults may differentially use linguistic constraints during sentence
      processing to cope with verbal working memory limitations. Probing syntactic
      semantic interactions, age differences were hypothesized to be confined to the
      use of syntactic constraints and to be accompanied by an increased reliance on
      semantic information. Two experiments varying in verbal working memory demands
      were conducted: the sequence length was increased from eight items in Experiment
      1 to 11 items in Experiment 2. We found the use of syntactic constraints to be
      compromised with aging, while the benefit of semantic information for sentence
      processing was comparable across age groups. Hence, we suggest that semantic
      information processing may become relatively more important for successful
      sentence processing with advancing adult age, possibly inducing a syntactic-to
      semantic-processing strategy shift. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30284855
TI  - Risk of progression to Alzheimer's disease for different neuropsychological Mild
      Cognitive Impairment subtypes: A hierarchical meta-analysis of longitudinal
      studies.
AB  - Mild Cognitive Impairment (MCI) is a heterogeneous condition between normal aging
      and dementia. Upon neuropsychological testing, MCI can be divided into 4 groups:
      single-domain amnestic MCI (sd-aMCI), multiple-domain amnestic MCI (md-aMCI),
      single- and multiple-domain nonamnestic MCI (sd-naMCI, md-naMCI). Some
      controversy exists about whether the risk of progression to Alzheimer's disease
      (risk-AD) is increased in all MCI subtypes. We meta-analyzed the risk-AD for 4
      MCI groups using random-effects metaregression with the Hierarchical Robust
      Variance Estimator and sample size, criterion for objective cognitive impairment,
      length of follow-up and source of recruitment as covariates. From a pool of 134
      available studies, 81 groups from 33 studies (N = 4,907) were meta-analyzed. All
      the studies were rated as having a high risk of bias. aMCI is overrepresented in
      studies from memory clinics. Multivariate analyses showed that md-aMCI had a
      similar risk-AD relative to sd-aMCI, whereas both sd-naMCI and md-naMCI showed a
      lower risk-AD compared with sd-aMCI. The risk-AD was significantly associated
      with differences in sample sizes across studies and between groups within
      studies. md-aMCI had a similar risk-AD relative to sd-aMCI in studies from memory
      clinics and in studies in the community. Several potential sources of bias such
      as blindness of AD diagnosis, the MCI diagnosis approach and the reporting of
      demographics were associated with the risk-AD. This work provides important data
      for use in both clinical and research scenarios. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 30284856
TI  - Higher self-stigma is related to lower likelihood of disclosing military sexual
      trauma during screening in female veterans.
AB  - OBJECTIVE: Recent prevalence estimates indicate 38% of female service
      members/veterans (SM/Vs) report military sexual trauma (MST). This estimate is
      higher than Veterans Affairs estimates, which suggest 28% report MST during
      screening. The discrepant estimate suggests possible barriers to disclosing MST,
      which are not well-identified in the literature. The current study examined
      whether being assaulted by a fellow unit member and stigma for seeking help to
      treat the sequelae of MST from self, unit leader/command, and romantic partners
      were correlates of MST nondisclosure among 209 female SM/Vs. METHOD: Participants
      completed a self-report questionnaire assessing MST nondisclosure, MST assailant
      characteristics, and stigma from the aforementioned sources as well as
      demographic, military, and mental health characteristics. Logistic regression
      analyses adjusting for military rank, MST severity, age, marital status and
      satisfaction, and probable mental health diagnoses determined whether being
      assaulted by a fellow unit member (yes/no) or stigma from various sources were
      associated with MST nondisclosure. RESULTS: Thirty-seven (17.70%) participants
      did not disclose MST during a previous screening. At the bivariate level,
      participants who did not disclose MST reported higher self-stigma and anticipated
      enacted stigma from unit leader/command and romantic partner. After adjusting for
      covariates, only higher self-stigma was associated with MST nondisclosure.
      CONCLUSIONS: Female veterans who report higher self-stigma were less likely to
      disclose their MST during screening. Such findings are consistent with previous
      literature demonstrating that self-stigma, relative to other forms of stigma,
      relates to lower help-seeking behaviors. Efforts to increase the disclosure of
      MST during screening should focus on reducing self-stigma. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 30284857
TI  - The role of common method variance in MMPI-2-RF response option augmentation.
AB  - Several studies have shown that response option augmentation (ROA), or increasing
      the number of response options of the Minnesota Multiphasic Personality Inventory
      (MMPI)-2-RF, improves the reliability of scale scores but does not improve
      convergent validity. However, these studies have not taken into account the
      response format of criterion measures, which may represent a form of common
      method variance (CMV). This study examined ROA with the MMPI-2-RF to determine
      whether number of response options is a source of CMV that may have affected
      previous estimates of convergent validity. The study used a repeated measures
      design with self-report and informant-report measures to examine differences
      between reliability and validity on scores from ROA and standard dichotomous MMPI
      2-RF RC scales. Results replicate those of previous studies, suggesting that ROA
      with the MMPI-2-RF leads to small increases in internal consistency, but near
      zero gains in convergent validity. Results are unable to support the proposition
      that CMV, due either to respondent or number of response options, meaningfully
      inflates correlations between measures with identical number of response options.
      These results consistently showing no meaningful increase in convergent validity
      across several studies may have implications for test authors deciding on the
      number of response options. Limitations and future directions are also discussed.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284859
TI  - Pain chronification and chronic pain impair a defensive behavior, but not the
      ability of acute pain to facilitate it, through the activation of an endogenous
      analgesia circuit.
AB  - The endogenous ability to decrease pain perception during life-threatening
      situations is crucial to the prevention of recuperative behaviors and to leave
      the subject free to engage in appropriated defensive responses. We have
      previously shown that acute pain activates the ascending nociceptive control-an
      endogenous analgesia circuit dependent on opioid mechanisms within nucleus
      accumbens-to facilitate the tonic immobility response, an innate defensive
      behavior. Now we asked whether chronic pain and pain chronification impairs
      either the tonic immobility response or the ability of acute pain to facilitate
      it by activating the ascending nociceptive control. We found a significant
      decrease in the duration of the tonic immobility response in rats during the
      induction and maintenance phases of the persistent mechanical hyperalgesia. This
      finding suggests that chronic pain and its development impair defensive
      responses. However, during the induction and maintenance phases of persistent
      hyperalgesia, the ascending nociceptive control activation, by a forepaw
      capsaicin injection, increased the tonic immobility response, an effect prevented
      by the blockade of MU-opioid receptors within nucleus accumbens. This finding
      suggests that pain chronification and chronic pain do not prevent the ability of
      acute pain to facilitate the defensive behavior of tonic immobility by activating
      the ascending nociceptive control. Therefore, although chronic pain states
      decrease the ability to engage in a defensive behavior, they may not prevent the
      expression of defensive behaviors during life-threatening situations accompanied
      by acute pain. The biological purpose of such a mechanism may be to increase the
      chances of survival of a wounded subject exposed to acute pain in a novel life
      threatening situation. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30284860
TI  - Emotion-modulated startle reflex during reappraisal: Probe timing and behavioral
      correlates.
AB  - Down-regulation of negative emotions has been shown to reliably inhibit the
      emotion-modulated startle reflex, but it remains unclear whether the timing of
      the startle probe influences the quantification of emotion regulation with this
      measure. Moreover, it is not known whether the degree of startle inhibition
      corresponds to the subjective attenuation of negative emotions. Therefore, the
      two main goals of the study were, first, to systematically analyze the effect of
      probe time on startle inhibition and, second, to explore the association between
      subjectively perceived down-regulation of arousal and valence and the degree of
      startle inhibition. We presented negative and neutral pictures to N = 47
      participants. Pictures were paired with the instruction to reappraise or to
      maintain the emotions elicited by these pictures. Probes were delivered at three
      different times during a 12.5-s regulation phase, and the startle response was
      measured with electromyography. Valence and arousal ratings were assessed after
      each trial. Results revealed no significant impact of probe time on startle
      inhibition during reappraisal. Startle inhibition and perceived down-regulation
      of arousal were significantly and positively correlated, whereas perceived down
      regulation of valence was not. The results provide important implications for
      future studies in terms of startle probe timing and shed light onto the
      interpretation of startle inhibition as an indicator of subjective attenuation of
      negative emotions. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284858
TI  - PTSD symptoms and alcohol-related problems among veterans: Temporal associations
      and vulnerability.
AB  - Posttraumatic stress disorder (PTSD) is associated with elevated risk of both
      alcohol use disorder (AUD) and related conduct problems, which are associated
      with behavioral and emotional dysregulation. We conducted an intensive
      longitudinal burst design study with 10 weeks of experience sampling over the
      course of 1.5 years with 250 veterans of recent conflicts. We tested time-series
      models of daily associations between posttraumatic stress symptoms (PTSS),
      alcohol dependence syndrome, and conduct problems. Exacerbations of PTSS
      predicted higher dependence syndrome and conduct problems the next day. This
      effect was significant after controlling for both concurrent (i.e., same-day)
      associations between drinking and the outcomes as well as the strength of
      associations between the outcomes from one day to the next (i.e.,
      autoregression). Affect lability and disinhibition were hypothesized
      vulnerability factors increasing the strength of within-person predictors of
      dependence syndrome and conduct problems. Lability and disinhibition were
      associated with greater dependence syndrome symptoms and conduct problems over
      the follow-up period. Consistent with expectation, lability rather than
      disinhibition increased the association between drinking and dependence syndrome
      as well as the strength of association between dependence syndrome symptoms from
      one day to the next. Moderating effects of disinhibition in the conduct problems
      model were not significant. Importantly, results indicated reciprocal
      associations over time. Lability potentiated the association between dependence
      syndrome symptoms and next day PTSS, whereas disinhibition potentiated the
      association between conduct problems and next day PTSS. Results demonstrate
      complex dynamic associations between PTSS, AUD symptoms, and conduct problems
      over time indicative of broad regulatory impairments. (PsycINFO Database Record
      (c) 2018 APA, all rights reserved).

PMID- 30284861
TI  - Rapid effects of sex steroids on zebra finch (Taeniopygia guttata) pair
      maintenance.
AB  - Although steroids are widely known to affect behavior through activation of
      nuclear/cytosolic receptors ("genomic" effects), steroids can also rapidly affect
      behavior via modulation of signal transduction pathways ("nongenomic," fast
      actions, or rapid effects). In zebra finches, there is evidence that sex steroids
      have context-specific effects on pair-maintenance behavior, on both acute and
      chronic timescales. Here, we quantified the effects of orally administered
      testosterone and 17beta-estradiol (E2) on pair-maintenance behavior. We show that
      E2 rapidly affects female, but not male, affiliative behavior profiles during a
      partner separation and reunion paradigm. More specifically, E2 rapidly (within 5
      15 min of administration) increased females' spatial proximity to a partner. This
      effect was present regardless of breeding condition (water restriction or water
      ad libitum). Combined, these results contribute to a growing body of evidence
      implicating sex steroids in the regulation of prosocial behavior. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30284862
TI  - Disassociating the relation between parents' math anxiety and children's math
      achievement: Long-term effects of a math app intervention.
AB  - Although parents' fears and worries about math-termed math anxiety-are negatively
      associated with their children's math achievement in early elementary school,
      access to an educational math app that 1st-grade children and parents use
      together can ameliorate this relation. Here we show that children of higher-math
      anxious parents learn less math during 1st-3rd grades, but this is not the case
      when families are given a math app (even after app use markedly decreases).
      Reducing the link between parents' math anxiety and their positive attitudes
      about math for their children helped to explain the sustained benefit of the math
      app. These findings indicate that interventions involving parents and children
      together can have powerful lasting effects on children's academic achievement and
      suggest that changes in parents' expectations for their children's potential for
      success in math, and the value they place on this success, play a role in these
      sustained effects. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284863
TI  - When thinking back can hold us back: How being a follower can affect women's loss
      aversion.
AB  - Despite the persistent gender gap in many organizational leadership positions,
      researchers have not yet examined objective predictors of this gap. A fully
      crossed 3 (Role Prime: leader, follower, control) * 2 (Gender Prime: present,
      absent) * 2 (Sex: male, female) experimental design examined the effect of group
      role (i.e., leader or follower) and gender on loss-aversion. Participants (192
      total; 96 female) were asked to name either their former or current leader
      ("superior") or follower ("subordinate"), compared with a no prime condition.
      Results suggest that women primed with a follower role were more loss-averse than
      men primed with a follower role, and were more loss-averse than women primed with
      the leader role or in the control condition. However, the role prime did not
      affect men's loss-aversion. The current research suggests that researchers and
      practitioners should consider the effects of group role on loss-aversion, as this
      may contribute to gender gaps in the workplace. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 30284864
TI  - Sleep moderates the association between routines and emotion regulation for
      toddlers in poverty.
AB  - Routines in the family are a potential source of resilience for at-risk children
      and support children's emerging emotion regulation. Meanwhile, inadequate sleep
      has been linked with deficits in cognitive processes to attend to environmental
      stimuli and with poor emotion regulation for children. The detrimental effects of
      poor sleep are potentially worse in low-income children. The aim of the current
      study was to examine the moderating role of sleep in the association between
      family routines and emotion regulation in toddlers in poverty. We analyzed data
      of 130 toddlers (24-31 months; 58% boys) from low-income, primarily African
      American families. Mothers completed questionnaires about child routines (Child
      Routines Questionnaire; CRQ; Wittig, 2005).To measure emotion regulation,
      toddlers completed an observed behavioral task meant to elicit frustration (Lab
      TAB-Locomotor Version; Goldsmith & Rothbart, 1991). As hypothesized, adequate
      sleep (> 11 hr) fully moderated the association between routines and observed
      emotion regulation. There was no effect of routines on emotion regulation for
      toddlers with inadequate amounts of sleep. Analyses controlled for toddler
      respiratory sinus arrhythmia (RSA) as well as maternal emotion dysregulation (the
      Emotional Dysregulation Scale; EDS; Westen, Muderrisoglu, Fowler, Shedler, &
      Koren, 1997). These results emphasize the importance of sufficient sleep in at
      risk toddlers. Furthermore, the results suggest that the effectiveness of family
      interventions focusing on family health to increase toddler emotion regulation
      could be improved by incorporating sleep interventions/routines. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30284866
TI  - Exploring the relative importance of normative and distinctive organizational
      preferences as predictors of work attitudes.
AB  - Profile approaches to operationalizing person-organization (P-O) fit as the
      within-person correlation between an individual's ideal organization
      characteristics and their actual organization characteristics regularly find
      strong associations between P-O fit and an individual's work attitudes. However,
      profile correlation indices and other overall indices of P-O fit regularly
      confound normative and distinctive components of fit-that is: the extent to which
      the person's organization culture fits the culture that would be preferred by the
      average person, and the extent to which their organization fits an individual's
      idiosyncratic preferences. Here, we show how these two normative and distinctive
      P-O fits can be differentiated and related to an individual's attitudes about
      their organization experience. Utilizing data from 723 participants from four
      samples, we show that the degree to which an individual's description of their
      organizational culture corresponds to the normative ideal organizational culture
      may account for nearly all of the large associations regularly found between
      overall P-O fit indices and positive workplace attitudes. In contrast, the degree
      of fit between an individual's work environment and their distinctive or
      idiosyncratic preferences may play a relatively small role in predicting the
      positive workplace attitudes. We discuss broader implications for the design of
      organizational cultures and the more general understanding of the nature of P-O
      fit. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284865
TI  - Virtual reality analgesia for burn joint flexibility: A randomized controlled
      trial.
AB  - OBJECTIVE: We conducted a randomized controlled study to determine the effects of
      virtual reality (VR) distraction on pain and range of motion (ROM) in patients
      hospitalized for burn care during active physical therapy exercises. METHOD:
      Thirty-nine participants aged 15 to 66 (M = 36) years with significant burn
      injuries (mean burn size = 14% TBSA) participated. Under therapist supervision,
      using a within-subjects design, participants performed unassisted active ROM
      exercises both with and without VR distraction in a randomized order. Therapists
      provided participants with instructions but did not physically assist with
      stretches. Maximum active ROM was measured using a goniometer. A 0-100 Graphic
      Rating Scale (GRS) was used to assess the cognitive, affective, and sensory
      components of pain. A GRS rating of the amount of "fun" during stretching served
      as a measure of positive experience. RESULTS: Participants reported lower mean
      GRS ratings during VR, relative to No VR, for worst pain, pain unpleasantness,
      and time spent thinking about pain. They also reported having a more positive
      experience during VR than during No VR. However, patients did not show greater
      ROM during VR. CONCLUSION: Immersive VR reduced pain during ROM exercises that
      were under the control of the patient. (PsycINFO Database Record (c) 2018 APA,
      all rights reserved).

PMID- 30284867
TI  - Latent classes of PTSD symptoms in veterans undergoing residential PTSD
      treatment.
AB  - Although most veterans in the Department of Veterans Affairs (VA) health system
      are treated for posttraumatic stress disorder (PTSD) in the outpatient setting,
      the VA has approximately 40 residential PTSD treatment facilities across the
      country for those requiring more intensive care. The symptom profiles of these
      veterans are poorly understood. Thus, the current study was designed to
      characterize classes of PTSD symptoms in a national sample of veterans undergoing
      residential treatment. We analyzed latent classes of PTSD symptoms among 2,452
      veterans entering VA PTSD residential treatment in fiscal year 2013. The model
      with the best fit was a 4-class model comprising a low symptom class, moderate
      symptom class with high reexperiencing symptoms, a moderate symptom class with
      high emotional numbing, and a high symptom class. Compared to classes identified
      in outpatient samples, these classes were similar in type but greater in
      severity. Classes differed by age, race/ethnicity, trauma type, co-occurring
      medical conditions, co-occurring psychiatric conditions, and social functioning.
      Compared to the moderate class with high emotional numbing, those in the moderate
      class with high reexperiencing symptoms were more likely to be non-White, have
      greater pain severity, greater sleep problems, and were less likely to be
      depressed. Our findings suggest that veterans in residential treatment who have
      more severe PTSD symptoms also experience other medical and psychosocial
      stressors. A better understanding of symptom profiles may help to create more
      individualized treatment planning and thus potentially improve care for these
      veterans. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284868
TI  - The generation effect and experimental design.
AB  - The generation effect is moderated by experimental design, as are a number of
      other encoding variables, such that the generation effect recall is typically
      larger in mixed-list than pure-list designs. In typical experiments on design
      effects, each study list is followed by its own recall test. Rowland, Littrell
      Baez, Sensenig, and DeLosh (2014) found that the testing effect was not moderated
      by experimental design using a procedures in which multiple study lists were
      followed by a single, end-of-session recall test over all lists. This may
      indicate an important difference between the testing effect and the set of
      effects (including generation) moderated by experimental design, or it may signal
      a more general limitation of design effects. Three experiments used the
      procedures of Rowland et al. and found that the generation effect was likewise
      unmoderated by experimental design: The generation effect was robust for pure
      lists and of equivalent size as with mixed lists. This was found for both a
      perceptual (letter transposition) and semantic (antonym) generation task. Along
      with prior research, these results constitute similarities between the generation
      and testing manipulations with respect to design effects and their limitations.
      This, in turn, implies a parallel between the mnemonic effects of retrieving
      information from semantic (generation effect) and episodic (testing effect)
      memory. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284869
TI  - Referential processing in 3- and 5-year-old children is egocentrically anchored.
AB  - An ongoing debate in the literature on language acquisition is whether preschool
      children process reference in an egocentric way or whether they spontaneously and
      by-default take their partner's perspective into account. The reported study
      implements a computerized referential task with a controlled trial presentation
      and simple verbal instructions. Contrary to the predictions of the partner
      specific view, entrained referential precedents give rise to faster processing
      for 3- and 5-year-old children, independently of whether the conversational
      partner is the same as in the lexical entrainment phase or not. Additionally,
      both age groups display a processing preference for the interaction with the same
      partner, be it for new or previously used referential descriptions. These results
      suggest that preschool children may adapt to their conversational partner;
      however, partner-specificity is encoded as low-level auditory-phonological
      priming rather than through inferences about a partner's perspective. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30284870
TI  - Unexpected conflict signals loom larger in a positive context: Evidence from
      context specific control adjustments.
AB  - One prominent feature of adaptive cognition in humans is the ability to flexibly
      adjust to changing task demands. In this respect, context-specific proportion
      congruency (CSPC) effects describe the phenomenon that participants learn to
      adapt to contexts of frequently occurring conflicts even when the upcoming
      context cannot be anticipated. Here, we aim to provide evidence that such CSPC
      effects strongly depend on the affective valence of the context. Participants had
      to categorize pictures as animals versus humans (Experiment 1), words as male
      versus female (Experiment 2), and food pictures as depicting cold or hot
      dishes/beverages (Experiment 3). Stimuli were laterally presented to the left or
      right, creating Simon-like response interference. Half of the stimuli were of
      positive valence, half of negative valence with valence always being task
      irrelevant. Positive or negative stimuli were associated with a high proportion
      of incongruent trials and a low proportion of congruent trials, respectively. In
      all three experiments, a CSPC effect was only significant when the high
      proportion of incongruent trials was associated with positive stimuli but reduced
      or even absent when the high proportion of incongruent trials was associated with
      negative stimuli. The findings further speak to the idea that it is the aversive
      nature of conflict stimuli that functions as a trigger for control adaptation.
      And such an unexpected aversive conflict signal looms larger when presented in a
      positive context than in a negative context. (PsycINFO Database Record (c) 2018
      APA, all rights reserved).

PMID- 30284871
TI  - Development of loneliness in midlife and old age: Its nature and correlates.
AB  - Research has long demonstrated that loneliness is a key risk factor for poor
      health. However, less is known about the development and predictors of loneliness
      across later adulthood. We examined these questions using two-wave data obtained
      5 years apart in the population-based Norwegian NorLAG study (N = 5,555; age 40
      80 years; 51% women). We considered direct measures of loneliness (asking
      directly about feeling lonely) and indirect measures (avoiding the term
      loneliness) and linked them to self-report data on personality and contact with
      friends, and to register data on socioeconomic (education, income, unemployment),
      physical health (sick leave, lifetime history of disability), and social factors
      (children, marriage/cohabitation, lifetime history of divorce and widowhood).
      Results indicated that levels of loneliness increased steadily for women, whereas
      men's levels followed a U-shaped curve, with highest loneliness at ages 40 and
      80. At age 40, loneliness declined between the two data waves, but with
      increasing age the decrease abated and turned into increases when loneliness was
      measured indirectly. Disability, no spouse/cohabiting partner, widowhood, and
      little contact with friends were each associated with more loneliness. Similarly,
      people high in emotional stability and extraversion reported less loneliness and
      experienced steeper loneliness declines on one or both loneliness measures. We
      take our results to illustrate the utility of combining self-report and register
      data and conclude that the development of loneliness across the second half of
      life is associated with both individual difference characteristics and aspects of
      social embedding. We discuss possible mechanisms underlying our findings and
      consider practical implications. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30284872
TI  - The relationship between response consistency in picture naming and storage
      impairment in people with semantic variant primary progressive aphasia.
AB  - OBJECTIVE: The progressive loss of stored knowledge about word meanings in
      semantic variant primary progressive aphasia (svPPA) has been attributed to an
      amodal "storage" deficit of the semantic system. Performance consistency has been
      proposed to be a key characteristic of storage deficits but has not been examined
      in close detail and larger participant cohorts. METHOD: We assessed whether 10
      people with svPPA showed consistency in picture naming across 3 closely
      consecutive sessions. We examined item-by-item consistency of naming accuracy and
      specific error types, while controlling for the effects of word-related variables
      such as word frequency, familiarity, and age of acquisition. RESULTS:
      Participants were very consistent in their accurate and inaccurate responses over
      and above any effects of the word-related variables. Analyses of error types that
      compared consistency of semantic errors, correct responses, and other error types
      (e.g., phonologically related errors, unrelated errors) revealed lower
      consistency. CONCLUSIONS: Our findings support the assumption that semantic
      features constituting semantic representations of objects are progressively lost
      in people with svPPA and are therefore consistently unavailable during naming.
      Variability in the production of error types occurs when distinctive features of
      an object are lost, resulting in the selection of semantically or visually
      similar items or in the failure to select an item and a response omission. The
      assessment of performance consistency sheds light on the underlying impairment of
      people with semantic deficits (semantic storage vs. access deficit). This can
      support the choice of an appropriate treatment technique to maintain or reteach
      semantic information. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30284873
TI  - State anxiety predicts cognitive performance in patients with Parkinson's
      disease.
AB  - OBJECTIVE: Anxiety is common in Parkinson's disease (PD) and frequently a
      comorbidity that appears alongside nonmotor symptoms such as cognitive deficits;
      however, the relationship between anxiety and cognition in PD remains poorly
      understood. The aim of this study was to investigate the relationship between
      anxiety and specific cognitive domains (e.g., attention/working memory, executive
      functions, memory, language, and visuospatial function). METHOD: A total of 48
      individuals with PD and 18 healthy controls were assessed using the State Trait
      Anxiety Inventory along with a comprehensive neuropsychological battery.
      Hierarchical multiple regression analysis was used to examine whether trait
      and/or state anxiety predicted deficits in overall cognitive function (Montreal
      Cognitive Assessment) and/or specific individual cognitive domains in the PD and
      healthy control samples while controlling for covariates such as age, depression
      (Geriatric Depression Scale), and Unified Parkinson's disease Rating Scale motor
      subsection-III (PD only). RESULTS: Results showed that state anxiety in PD
      significantly predicted performance across an array of cognitive domains, such as
      attention/working memory, executive functioning, memory, and language, whereas
      trait anxiety was a predictor only for executive functioning. In contrast, there
      was no significant relationship between state anxiety and visuospatial ability
      Conclusions: Overall, these findings highlight that performance in particular
      cognitive domains are associated with anxiety in PD. Thus, it may be critically
      important to consider and quantify the contribution of anxiety to cognitive
      performance when diagnosing and treating dementia and/or mild cognitive
      impairments in PD. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284874
TI  - Modelling picture naming in aphasia: The relationship between consistency and
      predictability of responses.
AB  - OBJECTIVE: Two aspects of aphasic picture naming were examined: response
      consistency, that is, the extent to which the accuracy of the response to the
      same stimulus is replicated in a successive examination, and response
      predictability, that is, the extent to which accuracy depends on the
      characteristics of each stimulus. METHODS: Thirty-eight aphasic participants were
      examined twice. The response pattern was the same across the 2 presentations
      (response stability) for 36 participants, who were classified into 3 groups
      according to the prevailing error-type (lexical-semantic, phonological, or a
      balance between the two error-types): Their item-consistency was quantified with
      Cohen's kappa. In each case the roles played by lexical frequency, precocity of
      acquisition and length of the target word, and visual complexity and image
      agreement of the stimulus picture were examined; the ability to predict response
      accuracy of a model simultaneously including these 5 variables was quantified by
      means of the McFadden index. Finally, the relationship between predictability
      (McFadden index) and consistency (Cohen's kappa) was analyzed. RESULTS: For 34 of
      36 participants, consistency was higher than chance. Consistency was directly
      correlated to the prevalence of lexical-semantic errors. On regression analysis,
      the relationship between consistency and predictability was significant.
      CONCLUSIONS: Response consistency reflects the existence of a clear difficulty
      gradient within the items of a battery. The significant relationship between
      consistency and error type suggests that, in principle, lexical-semantic errors
      might be more predictable than phonological errors based on the characteristics
      of each stimulus. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284875
TI  - Cross-lagged relation of leisure activity participation to trail making test
      performance 6 years later: Differential patterns in old age and very old age.
AB  - OBJECTIVE: We investigated cross-lagged relations between leisure activity
      participation and Trail Making Test (TMT) performance over 6 years and whether
      those reciprocal associations differed between individuals. METHOD: We analyzed
      data from 232 participants tested on performance in TMT Parts A and B as well as
      interviewed on leisure activity participation in 2 waves 6 years apart. Mean age
      in the Wave 1 was 73.42 years. Participants were also tested on vocabulary (Mill
      Hill scale) as a proxy indicator of crystallized intelligence and reported
      information on early and midlife cognitive reserve markers (education and
      occupation). Latent cross-lagged models were applied to investigate potential
      reciprocal activity-TMT relationships. RESULTS: The relation of leisure activity
      participation predicting TMT performance 6 years later was significantly larger
      than was the relation of TMT performance predicting later leisure activity
      participation. Statistically comparing different moderator groups revealed that
      this pattern was evident both in individuals with low education and in those with
      high education but, notably, emerged in only young-old adults (but not in old-old
      adults), in individuals with a low cognitive level of job in midlife (but not in
      those with a high cognitive level of job in midlife), and in individuals with
      high scores in vocabulary (but not in those with low scores in vocabulary).
      CONCLUSIONS: Late-life leisure activity participation may predict later cognitive
      status in terms of TMT performance, but individuals may markedly differ with
      respect to such effects. Implications for current cognitive reserve and
      neuropsychological aging research are discussed. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 30284876
TI  - Spanish translation and validation of the Interpersonal Needs Questionnaire.
AB  - The present study reports the multistage development and evaluation of a Spanish
      translation of the Interpersonal Needs Questionnaire (INQ). The INQ measures the
      constructs of thwarted belongingness and perceived burdensomeness, which the
      interpersonal theory of suicide proposes are proximal causes of suicidal desire.
      Participants were bilingual Hispanic college students in the United States (n =
      56), heritage Spanish-speaking college students in the United States (n = 281),
      college students in Spain (n = 1,016), psychiatric inpatients in Mexico (n =
      181), college students in Mexico (n = 239), and Spanish-speaking U.S. adults (n =
      104). Results indicated that a 9-item 2-factor solution (INQ-S-9) provided good
      fit. Multiple group analyses were also consistent with measurement invariance
      across nationalities and clinical severity. Finally, both subscale scores
      demonstrated good internal consistency, test-retest reliability, convergent
      validity, and concurrent associations with scores on measures of suicide
      ideation. Cultural considerations and implications for use in clinical and
      research settings are discussed. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30284878
TI  - Long-term outcomes from a self-help smoking cessation randomized controlled
      trial.
AB  - There is a need for effective smoking cessation interventions that can be
      disseminated easily in health care and other settings. We previously reported
      that an extended self-help intervention comprising intensive repeated mailings
      over 18 months improved abstinence rates through 6 months beyond the end of the
      intervention when compared to both a reduced version of the self-help materials
      and a traditional self-help booklet. This report extends the follow-up for an
      additional 6 months (30-months postbaseline) to examine long-term maintenance of
      the intervention effect. We hypothesized that the previously observed "dose
      response" effect of treatment intensity would be maintained. Participants were
      randomized to Traditional Self-Help (TSH, n = 638), Standard Repeated Mailings
      (SRM, n = 614), or Intensive Repeated Mailings (IRM, n = 622). TSH received an
      existing self-help smoking cessation booklet. SRM received 8 cessation booklets
      mailed over 12 months. IRM received monthly mailings of 10 booklets and
      additional material to enhance social support over 18 months. Follow-up
      assessments occurred every 6 months through 30 months. Data were collected 2010
      2013 and analyzed 2014-2017. At 1 year posttreatment, there was a linear dose
      effect with the highest abstinence rates observed in IRM (33%), followed by SRM
      (29%), and then TSH (23%; p = .002). Paired comparisons indicated that IRM was
      superior to TSH (p = .002). Results revealed a robust intervention effect for the
      intensive self-help intervention that was maintained 12 months after treatment
      completion. This further supports extended self-help as a low-cost intervention
      for smoking cessation. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30284877
TI  - Changes in implicit alcohol attitudes across adolescence, and associations with
      emerging alcohol use: Testing the reciprocal determinism hypothesis.
AB  - Implicit alcohol-related cognitions develop during adolescence and are thought to
      play an important role in the etiology of adolescent alcohol use. Rooted in
      reciprocal determinism, a developmental theory of alcohol-related cognitions, the
      current study sought to enhance our understanding of the development of automatic
      alcohol associations and their relationship with alcohol use. To provide a
      theoretically aligned test of reciprocal determinism, we used latent change score
      models to examine whether growth in automatic alcohol associations and alcohol
      use was related to each other (between-person effects) and whether each construct
      led to changes in the other over time (within-person effects). Adolescents (N =
      378) completed 4 annual assessments, spanning early to middle adolescence.
      Automatic alcohol associations were assessed with a Single Category Implicit
      Association Test, and we used a quadruple processing tree model to extract a more
      "process pure" index of these associations. Alcohol use increased from early to
      middle adolescence, as negative automatic alcohol associations weakened over that
      same time period. Although there was no support for between-person associations,
      on the within-person level, weak negative automatic alcohol associations at Waves
      2 and 3 were associated with increases in drinking at subsequent waves. Alcohol
      use did not significantly predict changes in automatic alcohol associations.
      Findings suggest the utility of distinguishing within- and between-person
      associations to understand the development of automatic alcohol associations and
      that automatic alcohol associations are prospectively associated with alcohol use
      and a potential target for intervention, one that becomes an increasingly salient
      influence on drinking as adolescence progresses. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 30284879
TI  - Depressive symptoms as predictors of alcohol problem domains and reinforcement
      among heavy drinking college students.
AB  - Heavy drinking among college students in the United States is common and results
      in a wide range of problems. Symptoms of depression are also common among college
      students and may exacerbate problems associated with heavy drinking, but to date
      most studies have been cross sectional and relied on an aggregate measure of
      alcohol problems. Further, depressive symptoms may also predict other elements of
      risk among heavy drinkers, including greater experience of substance-related
      reinforcement, and diminished experience of substance-free reinforcement. The
      current study examines depressive symptoms as a prospective predictor of changes
      in alcohol problem domains and reward variables in a sample of heavy drinking
      college students. Heavy drinking college students (N = 138) completed a survey
      assessing depressive symptoms, alcohol problems, and reinforcement at baseline
      and after a 12-month follow-up period. Multiple regressions examined the utility
      of depressive symptoms (DASS-21) in predicting alcohol problems, substance
      related reinforcement, and substance-free reinforcement at the 12-month follow-up
      after controlling for baseline drinking level and the baseline level of the
      relevant outcome variable. Baseline depressive symptoms predicted 12-month
      alcohol problems related to impaired control (i.e., drinking more than planned),
      self-perception, and self-care. Depressive symptoms also predicted lower 12-month
      substance-free, but not substance-related, reinforcement. Finally, change in
      depressive symptoms was associated with total alcohol problems, impaired control,
      self-perception, self-care, academic/occupational, and physiological dependence
      problems at 12-month follow-up. Heavy drinkers with depressive symptoms may
      benefit from interventions targeting alcohol problems that also increase access
      to and engagement in rewarding alternative activities. (PsycINFO Database Record
      (c) 2018 APA, all rights reserved).

PMID- 30284880
TI  - Trajectories of positive and negative affect across the transition to college:
      The role of daily interactions with parents and friends.
AB  - The college transition is uniquely challenging for many first-year students. Few
      studies have investigated developmental change in students' adjustment across
      this brief, but significant transition, nor the daily interpersonal dynamics that
      are associated with adjustment across this same time. Guided by ecological and
      stage-environment fit frameworks, this study examined trajectories of first-year
      students' positive and negative affect across the transition to college. Further,
      we examined daily interactions with parents and friends as predictors of these
      trajectories. Participants were 146 first-year college students from a large
      southwestern university entering their first semester of college (Mage = 17.82,
      SD = 0.50). Electronic ecological momentary assessments (EMAs) were administered
      to students twice weekly (maximum 49 observations) from July to December to
      assess daily experiences during the transition to college and across the first
      semester. Multilevel growth analyses showed that students reported a meaningful
      decrease in positive affect across the first semester, but stable levels of
      negative affect. Involvement and conflict with parents and friends predicted
      variability in these average changes, as well as daily affective states. As
      expected, greater involvement with parents and friends was associated with
      greater positive and less negative affect, and reports of conflict with parents
      and friends predicted negative affect experiences. Together, these findings
      suggest the importance of support from parents and friends during the initial
      adaptation to college, as well as the potential undermining role of conflict with
      significant others. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284881
TI  - Patterns of parental emotion-related discourse and links with children's problem
      behaviors: A person-centered approach.
AB  - Research demonstrates that parents' emotion-related discourse during reminiscing
      shapes children's psychosocial outcomes, yet little is known about how different
      forms of parental emotion-related discourse work in combination. The present
      study takes a person-centered approach to better understand the relation of
      multiple forms of parental emotion discourse during reminiscing with problem
      behaviors in early childhood, as well as child influences on parents' emotion
      discourse during reminiscing. Specifically, we simultaneously examine three forms
      of parents' emotion-related discourse (emotion coaching and dismissing, emotion
      explanations, and elaboration) using cluster analysis to determine parents'
      patterns of these three discourse forms during discussion about past events.
      Parents and their preschool-aged children (n = 154) completed a parent-child
      reminiscing task. Transcripts were coded for emotion coaching and dismissing,
      emotion explanations, and elaboration. Parents reported on children's
      internalizing and externalizing behaviors, temperament, and gender, and children
      completed a language assessment. Cluster analyses revealed three parental
      discourse patterns: elaboration/negative emotion emphasis, positive and negative
      emotion emphasis, and low emotion discourse. Children's receptive language was
      associated with parents' membership in the low emotion discourse cluster.
      Children's temperament and gender were unrelated to parental emotion-related
      discourse patterns. Parents in the positive and negative emotion emphasis cluster
      had children with fewer internalizing behaviors compared to both other clusters,
      and parents in the elaboration/negative emotion emphasis cluster had children
      with more internalizing behaviors compared to both other clusters. Findings
      support the utility of a person-centered approach in providing a holistic view of
      parents' use of multiple emotion socialization strategies during reminiscing.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284882
TI  - Infants' selective use of reliable cues in multidimensional language input.
AB  - Learning always happens from input that contains multiple structures and multiple
      sources of variability. Though infants possess learning mechanisms to locate
      structure in the world, lab-based experiments have rarely probed how infants
      contend with input that contains many different structures and cues. Two
      experiments explored infants' use of two naturally occurring sources of
      variability-different sounds and different people-to detect regularities in
      language. Monolingual infants (9-10 months) heard a male and female talker
      produce two different speech streams, one of which followed a deterministic
      pattern (e.g., AAB, le-le-di) and one of which did not. For half of the infants,
      each speaker produced only one of the streams; for the other half of the infants,
      each speaker produced 50% of each stream. In Experiment 1, each stream consisted
      of distinct sounds, and infants successfully demonstrated learning regardless of
      the correspondence between speaker and stream. In Experiment 2, each stream
      consisted of the same sounds, and infants failed to show learning, even when
      speakers provided a perfect cue for separating each stream. Thus, monolingual
      infants can learn in the presence of multiple speech streams, but these
      experiments suggest that infants may rely more on sound-based rather than speaker
      based distinctions when breaking into the structure of incoming information. This
      selective use of some cues over others highlights infants' ability to adaptively
      focus on distinctions that are most likely to be useful as they sort through
      their inherently multidimensional surroundings. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 30284884
TI  - Secret to friendship: Children make inferences about friendship based on secret
      sharing.
AB  - Secrets carry valuable social information. Because the content of secrets can be
      damaging to the secret-keeper's reputation, people should only disclose their
      secrets to people whom they trust. Therefore, tracking which people know each
      other's secrets can be used as cue of social relationships: If one person tells
      another person a secret, those people are likely friends. Here, in 5 studies with
      3- to 12-year-old children (total N = 452), we examined the developmental
      trajectory of reasoning about secret sharing as an indication of third-party
      friendship. By age 6, but not before, children expected that a person would be
      friends with someone that she told a secret. We replicated this main finding
      across four studies by comparing secret sharing to other cues of affiliation.
      Children treated sharing a secret as a stronger cue to friendship than sharing a
      physical object (Study 1), sharing a fact (Studies 2-4), or sharing membership on
      the same sports team (Study 3). Although younger children did not understand that
      secret sharing indicated friendship, they did expect people to be more likely to
      disclose their secrets to friends than to nonfriends (Study 5). Taken together,
      our results indicate that children understand the social significance of sharing
      secrets and use secret sharing to make important predictions about the social
      world. Specifically, children infer social relationships based on which people
      know each other's secrets and expect others to share secrets selectivity with
      friends. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284885
TI  - The role of shame in chronic peer victimization.
AB  - Emotional reactions to peer victimization may increase risk for subsequent peer
      victimization. In the present study, we investigated whether shame mediated the
      development of chronic peer victimization, i.e., young people's experiences of
      being bullied persistently across time. We used a multiple mediation model to
      test the indirect effects of Time-1 victimization on Time-3 victimization (1 year
      later) through 4 Time-2 shame-related variables (characterological, bodily, and
      behavioral shame; shame proneness) for 396 youth (10-13 years of age). The total
      indirect effect of Time-1 victimization on Time-3 victimization through the 4
      shame-related mediators was statistically significant. Analyses revealed specific
      indirect positive effects for bodily shame and shame proneness. Findings suggest
      that shame may be an emotional mechanism underlying chronic peer victimization.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284883
TI  - Family nurture intervention for preterm infants facilitates positive mother
      infant face-to-face engagement at 4 months.
AB  - Although preterm infants are at risk for social deficits, interventions to
      improve mother-infant interaction in the neonatal intensive care unit (NICU) are
      not part of standard care (SC). Study participants were a subset from a
      randomized controlled trial of a new intervention for premature infants, the
      Family Nurture Intervention (FNI), designed to help mothers and infants establish
      an emotional connection. At infants' 4 months corrected age, mother-infant face
      to-face interaction was filmed and coded on a 1-s time base for mother touch,
      infant vocal affect, mother gaze, and infant gaze. Time-series models assessed
      self- and interactive contingency. Comparing FNI to SC dyads, FNI mothers showed
      more touch and calmer touch patterns, and FNI infants showed more angry-protest
      but less cry. In maternal touch self-contingency, FNI mothers were more likely to
      sustain positive touch and to repair moments of negative touch by transitioning
      to positive touch. In maternal touch interactive contingency, when infants looked
      at mothers, FNI mothers were likely to respond with more positive touch. In
      infant vocal affect self-contingency, FNI infants were more likely to sustain
      positive vocal affect and to transition from negative to positive vocal affect.
      In maternal gaze interactive contingency, following infants' looking at mother,
      FNI mothers of male infants were more likely to look at their sons. In maternal
      gaze self-contingency, following mothers' looking away, FNI mothers of male
      infants were more likely to look at their sons. Documentation of positive effects
      of the FNI for 4-month mother-infant face-to-face communication is useful
      clinically and has important implications for an improved developmental
      trajectory of these infants. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30284886
TI  - Evaluation of schedule frequency and density when monitoring progress with
      curriculum-based measurement.
AB  - School-based professionals often use curriculum-based measurement of reading (CBM
      R) to monitor the progress of students with reading difficulties. Much of the
      extant CBM-R progress monitoring research has focused on its use for making group
      level decisions, and less is known about using CBM-R to make decisions at the
      individual level. To inform the administration and use of CBM-R progress
      monitoring data, the current study evaluated the utility of 4 progress monitoring
      schedules that differed in frequency (once or twice weekly) and density (1 or 3
      probes). Participants included 79 students (43% female; 51% White, 25% Hispanic
      or Latino, 11% Black or African American, 1% other, 12% unknown) in Grades 2 (n =
      45) and 4 (n = 34) who were monitored across 10 weeks (February to May).
      Consistent with a focus on individual-level decision making, we used regression
      and mixed-factorial analysis of variances (ANOVAs) to evaluate the effect of
      progress monitoring schedule frequency, schedule density, grade level, and their
      interaction effects on CBM-R intercept, slope, SE of the slope (SEb), and SE of
      the estimate (SEE). Results revealed that (a) progress monitoring schedule
      frequency and density influenced the magnitude of SEb, (b) density had a
      significant but negligible impact on SEE, and (c) grade level had a significant
      effect on slope and intercept. None of the interaction effects were statistically
      significant. Findings from this study have implications for practitioners and
      researchers aiming to monitor students' progress with CBM-R. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 30284887
TI  - Adapting COMPASS for youth with ASD to improve transition outcomes using
      implementation science.
AB  - Implementation science provides guidance on adapting existing evidence based
      practices (EBPs) by incorporating implementation concerns from the start. Focus
      group methodology was used to understand barriers and facilitators of transition
      planning and implementation for students with autism spectrum disorder (ASD) who
      often experience disparate postsecondary outcomes compared to peers. Results were
      used to modify an evidence-based consultation intervention originally applied to
      young students with ASD, called the Collaborative Model for Promoting Competence
      and Success (COMPASS; Ruble, Dalrymple, & McGrew, 2012). Because consultation is
      a multilevel EBP, two existing implementation science frameworks were used to
      guide adaptation: the Framework for Evidence Based Implementation and
      Intervention Practices (Dunst & Trivette, 2012) and the Consolidated Framework
      for Implementation Research (Damschroder et al., 2009). The purpose of this
      article is to describe a process of adaptation of COMPASS that may be useful for
      other implementation science studies of consultation interventions, teacher
      acceptability, feasibility, and burden, and parent/student satisfaction with the
      adapted intervention. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30284888
TI  - Adolescents' self-report of school satisfaction: The interaction between
      disability and gender.
AB  - School satisfaction is a critical aspect of well-being for every child and
      adolescent. Yet studies have rarely investigated whether school satisfaction
      varies depending upon participant characteristics and school-related social
      factors. Here we investigated whether disability and gender moderate adolescents'
      self-report of school satisfaction. We also explored the role of mediating
      variables such as teacher support, parent support, and relationships with peers
      (including friendships and also bullying). Our analysis of data from 3,830
      adolescents revealed a significant interaction between disability and gender.
      Girls with disabilities reported the lowest school satisfaction, an effect that
      appeared to be more strongly mediated by perceived lack of teacher support than
      other variables. Our findings are novel in disaggregating school satisfaction
      data by both disability and gender to reveal an interaction between these
      variables and in investigating the role of mediating variables relating to school
      related social factors. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30284889
TI  - A comprehensive method of single-case data analysis: Interrupted Time-Series
      Simulation (ITSSIM).
AB  - Single-case experimental methods are used across a range of educational and
      psychological research. Single-case data are analyzed with a variety of methods,
      but no statistic has demonstrated clear superiority over other methods. The time
      series nature of single-case designs requires special consideration for baseline
      trend and autocorrelation when estimating intervention effect size. However,
      standard correction methods are limited because they assume precise statistical
      estimation of trend and autocorrelation. Unlike standard correction methods,
      Monte Carlo simulation methods can address the poor precision of single-case
      effect size indices. This paper presents the rationale for a new simulation
      method, Interrupted Time-Series Simulation (ITSSIM). A small field test was also
      conducted, and ITSSIM performed similarly to sophisticated multilevel methods for
      single-case research. ITSSIM is accessible as a free software application that
      requires no prior knowledge of statistical computing or syntax. ITSSIM may be
      used to estimate the effect size of a single interrupted time-series (AB design),
      and multiple ITSSIM effect size estimates may be combined via meta-analysis.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284890
TI  - Brief homework intervention for adolescents with ADHD: Trajectories and
      predictors of response.
AB  - In the present study, we sought to examine response trajectories to brief (11
      week) school-based homework interventions and factors that may help schools
      predict responses. Participants included 222 middle-school students (72% boys;
      Mage = 12.00 years, SD = 1.02) who had been diagnosed with attention
      deficit/hyperactivity disorder (ADHD) and had received either a contingency
      management or skills-based intervention for homework problems. Both interventions
      included 16 20-min student meetings with a school counselor and two parent
      meetings. Trajectories of response for ratings of homework problems and
      assignment completion were examined from baseline to a 6-month follow-up using
      growth-mixture models. Baseline variables routinely measured in school settings,
      including grade-point average (GPA), math and reading achievement, and
      externalizing and internalizing symptoms, were examined as predictors of
      treatment-response trajectories. The majority of students (68-81%) showed
      positive treatment response across outcomes. However, trajectories of students
      who did not respond to intervention were identified for each outcome. Baseline
      GPA significantly predicted trajectories for all outcomes and achievement scores
      significantly predicted trajectories of teacher-reported homework performance and
      parent-reported homework problems, such that youth with relatively higher
      baseline GPAs and achievement were most likely to respond. In contrast, neither
      externalizing nor internalizing symptoms were significant predictors of response
      trajectories. Schools can use GPA and academic-achievement data to determine
      whether brief school-based interventions for homework problems are likely to
      succeed. Students with ADHD who display severe academic impairment (i.e., GPA
      lower than 2.0 at baseline) may benefit from a more long-term, intensive
      intervention. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284891
TI  - The new psychometrics: Comment on Appelbaum et al. (2018).
AB  - This comment attempts to correct misconceptions about psychometric measurement in
      the American Psychologist article "Journal Article Reporting Standards for
      Quantitative Research in Psychology" (Appelbaum et al., 2018) by offering an
      outline of what the author calls the new psychometrics. The new psychometrics
      argues for replacing "construct validation" with construct-to-measure validation,
      abandoning "convergent validation" in favor of content validation requiring
      correspondence of the content of the measure with the content of the construct
      definition, and restricting the term reliability to mean only the precision of
      scores from the measure. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30284892
TI  - Intent of reporting standards: Reply to Rossiter (2018).
AB  - In this reply to Rossiter (2018), we note that the goal of developing Journal
      Article Reporting Standards has been to specify the kinds of information that
      should be provided to the readers of scientific articles in order to allow
      maximal understanding of the work being reported-in the case of psychometrics,
      information that demonstrates the underlying adequacy of the measures used in the
      research being reported. Although we illustrate some kinds of items that might be
      utilized to make these demonstrations, the illustrations are not proscriptive.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284893
TI  - A framework for disentangling the hyperbolic truth of neurofeedback: Comment on
      Thibault and Raz (2017).
AB  - In this comment, we propose a theoretical framework for disentangling the
      potentially multiple elements driving the effects of electroencephalogram (EEG)
      neurofeedback (EEG-nf) to clarify the roadmap for research in the field. Three
      questions are identified: (a) Do EEG-nf effects originate from a placebo effect
      related to the technological environment of a neurofeedback session? (b) Do EEG
      nf effects originate from a nonspecific effect of cognitive brain training during
      neurofeedback? If so, a cognitive training would be underpinned by the brain
      activity regulation loop but this training would not be specifically related to
      the neurophysiological biomarker chosen. (c) Do EEG-nf effects originate from a
      specific effect of cognitive brain training? If so, the effects of EEG-nf would
      be explained by the training of the specific neurophysiological biomarker chosen,
      depending on the pathophysiological mechanism(s) of the disorder. The proposed
      framework might thus allow to understand to what degree each of these level
      contribute to the effects of EEG-nf on the brain and behavior in view of the
      psychosocial variables involved. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30284894
TI  - A consensus framework for neurofeedback research (and the perils of unfounded
      neuroreductionism): Reply to Micoulaud-Franchi and Fovet (2018).
AB  - We were pleased to read the constructive commentary (Micoulaud-Franchi & Fovet,
      2018) on our original piece (Thibault & Raz, 2017). In this response, we build on
      the theoretical framework for studying neurofeedback that the commentators sketch
      out while pointing out potential caveats to adopting a neuroreductionist
      approach. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284895
TI  - Ronald E. Fox (1936-2018).
AB  - Presents an obituary of Ronald E. Fox (1936-2018). Fox was a visionary,
      trailblazer, and leader in the practice of psychology for over 50 years, renowned
      for his ability to bring psychologists together to meet society's most pressing
      needs. Fox envisioned a broad social role for professional psychology, moving
      beyond psychotherapy for people with psychological problems to encompass general
      health, prevention, and well-being. He also had a long history of involvement in
      the APA. He was always a step or two ahead of us-creating the Practice
      Directorate, supporting the APA's reorganization that created the directorate
      structure, urging all of us to contribute to political action. He was recognized
      for his contributions with many awards, including the Distinguished Career
      Contributions to Practice of Psychology Gold Medal Award from the American
      Psychological Foundation (1994) and the Raymond D. Fowler Award for Outstanding
      Contributions to APA (2009). (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30284896
TI  - Henry Gleitman (1925-2015).
AB  - Presents an obituary of Henry Gleitman (1925-2015). Gleitman was an author of
      major papers in animal learning, memory, theater, and the psychology of language,
      including one book with Lila Gleitman (Phrase and Paraphrase, 1970). Gleitman was
      among the very best teachers in the history of psychology. He taught introductory
      psychology about 100 times, engaging the minds of some 30,000 students, each
      exposed to his enlightening, expansive, and entertaining synthesis of psychology.
      Gleitman came to the University of Pennsylvania in 1964 as Professor and Chair of
      Psychology. Over a 5-year period, he shaped the department into a first-rate
      teaching center for both undergraduate and graduate students, and demonstrated
      the compatibility and mutually reinforcing values of teaching and research. The
      University of Pennsylvania was uniquely blessed to count him among its faculty
      for 50 years (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30284897
TI  - Leon J. Kamin (1927-2017).
AB  - Presents an obituary of Leon J. Kamin (1927-2017), former chair of the Psychology
      Department at Northeastern University. Over the course of his career, Kamin
      demonstrated a rare combination of skills as a researcher, scholar, and
      administrator. Early in his career, Kamin developed an influential line of
      research on conditioning. In fact, a conditioning effect, the Kamin (blocking)
      effect, is named after him. Later in his career, he became interested in the
      heritability of intelligence, leading to his debunking of Cyril Burt's famous
      twin studies and the publication of his extremely influential book The Science
      and Politics of IQ (1974). Kamin also enjoyed great success as an administrator,
      serving as chair in each of the departments in which he worked. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30284898
TI  - Joseph White (1932-2017).
AB  - Presents an obituary of Joseph White (1932-2017), often called "the godfather of
      Black psychology." During a distinguished 56-year career, White held many
      professional roles, perhaps none more profound than that of mentor. Additionally,
      White served as a (supervising) psychologist to five hospitals and three clinical
      practices. He served as chairman of the California State Psychology Licensing
      Board for 3 years. He was also a member of the Board of Trustees of The Menninger
      Foundation in Houston, Texas, and held the title of professor emeritus of
      psychology and psychiatry at the University of California, Irvine, where he spent
      most of his career as a professor and director of ethnic studies and cross
      cultural programs. White personified a socially engaged psychologist. He
      continually promoted the goals of multiculturalism and social justice through his
      practice and scholarship. The author or coauthor of numerous articles and books,
      he was a founder of the Association of Black Psychologists (ABPsi) and a pioneer
      in the field of Black psychology. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30284899
TI  - Wilse Bernard (Bernie) Webb (1920-2018).
AB  - Presents an obituary of Wilse Bernard (Bernie) Webb (1920-2018). Webb was an
      effective researcher and administrator but also an overall colorful personality.
      His evolving research career was highlighted by work on learning mechanisms and
      studies of aircraft accidents. He became most widely known for his important
      early work on biological rhythms, individual difference, effects of sleep
      deprivation, and theories of sleep. In 1958 Bernie was appointed psychology chair
      at the University of Florida, which was developing as a research university.
      During his years as chair, the size and scope of the department increased,
      graduate research professorships were established, and plans were laid for a new
      psychology building. In addition to receiving various awards, he served as
      president of the Southern Society for Philosophy and Psychology, the Southeastern
      Psychological Association, the American Psychological Association's (APA)
      Division of Teaching, as well as its Division of the History of Psychology. He
      also served two terms on the APA Board of Directors. (PsycINFO Database Record
      (c) 2018 APA, all rights reserved).

PMID- 30284900
TI  - Joseph French (1928-2018).
AB  - Presents an obituary of Joseph French (1928 -2018). At Pennsylvania State
      University (PSU), French developed one of the earliest doctoral school psychology
      programs, directed the School Psychology Clinic, and for 7 years was head of the
      Department of Special Education. He was president of the Association for the
      Gifted (1969) and the Division of School Psychology of the American Psychological
      Association (APA; 1976-1977) and held other positions with the Council for
      Exceptional Children, the American Counseling Association, the APA Division of
      School Psychology, and the Pennsylvania Psychological Association (PPA). He will
      be remembered as a professional and family role model who excelled in
      contributing to the development and history of school psychology, special
      education, test development, and training. (PsycINFO Database Record (c) 2018
      APA, all rights reserved).

PMID- 30284901
TI  - "Journal article reporting standards for quantitative research in psychology: The
      APA Publications and Communications Board Task Force Report": Correction to
      Appelbaum et al. (2018).
AB  - Reports an error in "Journal article reporting standards for quantitative
      research in psychology: The APA Publications and Communications Board task force
      report" by Mark Appelbaum, Harris Cooper, Rex B. Kline, Evan Mayo-Wilson, Arthur
      M. Nezu and Stephen M. Rao (American Psychologist, 2018[Jan], Vol 73[1], 3-25).
      In the article, there was a citation error. In the "Clinical Trials" subsection
      in the section, "Reporting Standards for Studies With an Experimental
      Manipulation" (p. 13), the reference to the World Medical Association's
      Declaration of Helsinki should be to the 2008 version of the declaration. The
      sentence should read as follows: From an ethical perspective, the Declaration of
      Helsinki, which is the set of ethical principles regarding human experimentation
      developed by the World Medical Association, Inc. (2008), stated that "every
      clinical trial must be registered in a publicly accessible database before
      recruitment of the first subject" (Item 19, p. 3). The corrected reference, on p.
      25, is also presented in the erratum. (The following abstract of the original
      article appeared in record 2018-00750-002.) Following a review of extant
      reporting standards for scientific publication, and reviewing 10 years of
      experience since publication of the first set of reporting standards by the
      American Psychological Association (APA; APA Publications and Communications
      Board Working Group on Journal Article Reporting Standards, 2008), the APA
      Working Group on Quantitative Research Reporting Standards recommended some
      modifications to the original standards. Examples of modifications include
      division of hypotheses, analyses, and conclusions into 3 groupings (primary,
      secondary, and exploratory) and some changes to the section on meta-analysis.
      Several new modules are included that report standards for observational studies,
      clinical trials, longitudinal studies, replication studies, and N-of-1 studies.
      In addition, standards for analytic methods with unique characteristics and
      output (structural equation modeling and Bayesian analysis) are included. These
      proposals were accepted by the Publications and Communications Board of APA and
      supersede the standards included in the 6th edition of the Publication Manual of
      the American Psychological Association (APA, 2010). (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 30284902
TI  - Todani Ic cystic dilatation of the bile duct.
AB  - The congenital dilation of the bile duct is an infrequent pathology in western
      countries and is associated with the female sex. It is usually diagnosed
      clinically with complementary tests and evaluated at an early age and also
      appears frequently in adults. These dilatations are grouped into five types
      according to Todani's classification, including type Ic (Figure 1). The treatment
      of choice for dilatations of the biliary duct Todani type I is the complete
      excision of the biliary tract due to the susceptibility of malignant
      degeneration. A reconstruction is performed via a hepaticojejunostomy with a Roux
      en-Y loop. Although in non-malignant cases, a papillotomy with prophylactic stent
      placement using ERCP can be performed as an alternative. We present the case of a
      54-year-old female with a history of high blood pressure, she was examined due to
      generalized abdominal pain which was unrelated to food intake. The blood test did
      not identify any alterations of interest. Ultrasound identified a fusiform
      dilation of the common bile duct occupied by lithiasis. ERCP was attempted due to
      choledocholithiasis, but the procedure was abandoned as it was not feasible to
      channel the duodenal papilla. The study was completed with NMR cholangiography
      (transverse plane [Figure 2] and coronal plane [Figure 3]), identifying a diffuse
      fusiform dilatation of the common bile duct and common hepatic duct, compatible
      with congenital cystic lesion Todani type Ic. Finally, the patient underwent a
      hepaticojejunostomy after sectioning of the main bile duct and extraction of
      choledocholithiasis.

PMID- 30284903
TI  - Bile acid malabsorption in patients with chronic diarrhea and Crohn's disease.
AB  - INTRODUCTION AND AIM: Crohn's disease (CD) is a form of inflammatory bowel
      disease and is mainly characterized by diarrhea and abdominal pain. The aim of
      our study was to analyze the usefulness of performing a 75SeHCAT scan in CD
      patients with chronic diarrhea and suspected bile acid malabsorption (BAM). In
      addition, we aimed to determine whether there was a relationship with the
      clinical features of the disease and a previous bowel resection. PATIENTS AND
      METHODS: this was an observational cross-sectional study of 39 patients with a
      diagnosis of CD and chronic diarrhea. All cases underwent a 75SeHCAT scan for BAM
      diagnosis, after discarding disease activity. RESULTS: the study cohort included
      19 females and 20 males. The median age was 44 years and the majority of patients
      were A2 L1 B1 according to the Montreal classification; 84.6% of patients had
      undergone a previous bowel resection. BAM was present in 97.4% of patients (100%
      and 83.3% of patients with and without previous surgery, respectively), which was
      severe in 92.1% of cases. Treatment with bile acid sequestrants was initiated and
      a favorable response was obtained in 72.2% of patients. The relationship between
      BAM degree (moderate or severe), bowel surgery and the response to bile acid
      sequestrant treatment was also analyzed but not statistically significant.
      CONCLUSION: BAM is a frequent cause of diarrhea in CD patients in endoscopic or
      radiological remission. This condition was present in all patients with a history
      of a bowel resection. A response to bile acid sequestrants treatment was observed
      in 73% of patients.

PMID- 30284904
TI  - Treatment of graft-versus-host disease with mesenchymal cells as a complication
      of a liver transplantation.
AB  - We present the case of a liver transplant (LT) recipient donor who developed
      graft versus host disease (GVHD). The main features were cutaneous rash, diarrhea
      and pancytopenia. Mesenchymal cells were administered as part of the treatment.
      This is the first case of a patient with GVHD after LT reported to date. Despite
      the treatment, there was no improvement in aplasia or gastrointestinal symptoms
      and the patient died due to a disseminated infection.

PMID- 30284905
TI  - Colorectal cancer screening and survival.
AB  - It is difficult to resist the undeniable allure of screening as a means to
      diagnose common, potentially serious diseases before their natural history
      reaches an incurable stage. Colorectal cancer (CRC) is a classical example where
      the benefits seem to be within reach: we have technologies available that allow
      its diagnosis before symptoms or signs develop, at a reasonable cost, and using
      methods acceptable by a significant percentage of the population.

PMID- 30284906
TI  - Comparison of long course and short course preoperative radiotherapy in the
      treatment of locally advanced rectal cancer: a systematic review and meta
      analysis.
AB  - BACKGROUND: rectal cancer (RC) is one of the most prevalent malignancies
      worldwide and different preoperative radiotherapies may lead to different
      outcomes. This meta-analysis aimed to compare the effectiveness of long-course
      (LC) and short-course radiotherapy (SC), with or without chemotherapy, for
      locally advanced rectal cancer. METHODS: studies published up to March 31st 2018
      were retrieved from PubMed, Medline, Cochrane and EMABSE. Randomized control or
      consort control trials that reported the outcomes of short or long course
      radiotherapy were eligible. Either a fixed or random effects model was used to
      access the overall combined risk estimates. RESULTS: sixteen studies with a total
      of 2,773 RC patients were included in the analysis. There were no significant
      differences between LC and SC therapies with regard to the following:
      pathological complete response (PCR) (I2 = 78%, p < 0.05, RR = 0.54, 95% CI: 0.26
      1.10); tumor downstaging (I2 = 79%, p < 0.05, RR = 0.83, 95% CI: 0.58-1.17);
      local recurrences (I2 = 22%, p = 0.27, RR = 0.55, 95% CI: 0.26-1.16); distant
      metastases (I2 = 29%, p = 0.22, RR = 1.03, 95% CI: 0.77-1.37); mortality (I2 =
      0%, p = 0.78, RR = 0.95, 95% CI: 0.78-1.15) and serious late toxicity (I2 = 74%,
      p = 0.01, RR = 1.10, 95% CI: 0.37-3.26). In the subgroup analysis, LC had a
      better PCR and tumor downstaging rate compared with SC in the RCT subgroup.
      Besides, LC also presented a better PCR rate compared with SC without
      chemotherapy. CONCLUSIONS: LC and SC are both effective in the preoperative
      treatment of RC with regard to PCR, tumor downstaging, local recurrences, distant
      metastases, mortality and serious late toxicity. Furthermore, chemotherapy may
      enhance the efficacy of preoperative treatment.

PMID- 30284907
TI  - A rare case of acute obstructive suppurative pancreatic ductitis associated with
      ERCP.
AB  - A 76-year-old male with severe abdominal pain and a high fever was admitted to
      our hospital. The patient underwent a therapeutic endoscopic retrograde
      Cholangiopancreatography (ERCP) procedure one month previously due to acute
      biliary pancreatitis and a plastic biliary stent (8.5F) was placed. A follow-up
      computed tomography (CT) scan identified a huge cyst lesion in the body of
      pancreas, which was initially misdiagnosed as a pseudocyst. The patient
      progressed to severe sepsis and septic shock soon after admission.

PMID- 30284908
TI  - Vitamin D deficiency in outpatients with inflammatory bowel disease: prevalence
      and association with clinical-biological activity.
AB  - INTRODUCTION: there are few data on the prevalence of vitamin D deficiency in
      patients with inflammatory bowel disease (IBD) in Spain. A deficiency could be
      associated with a worse course of the disease. AIM: to determine the prevalence
      of 25-hydroxyvitamin D (25OHD) deficiency in a cohort of outpatients with IBD and
      assess its association with clinical and biological activity, quality of life and
      psychological symptoms. METHODS: a cross-sectional, single-center observational
      study was performed. The study variables were obtained via clinical interviews,
      medical chart review and validated questionnaires (Hospital Anxiety and
      Depression Scale and Short Quality of Life in Inflammatory Bowel Disease
      Questionnaire). 25OHD was measured in the same laboratory by an electro
      chemiluminescence immunoassay. RESULTS: the study included 224 patients. The
      prevalence of vitamin D deficiency in Crohn's disease and ulcerative colitis was
      33.3% and 20.3%, respectively. In Crohn's disease, vitamin D deficiency was
      associated with a higher clinical activity (p < 0.001) and a higher concentration
      of fecal calprotectin (p = 0.01). In ulcerative colitis, it was associated with
      clinical activity (p < 0.001), the use of steroids during the last six months (p
      = 0.001) and hospital admission during the previous year (p = 0.003). A sub
      analysis of 149 patients failed to detect an association between vitamin D and
      quality of life or the scores of the Hospital Anxiety and Depression Scale.
      CONCLUSIONS: vitamin D deficiency is common in patients with inflammatory bowel
      disease. An association was found between vitamin D concentration and clinical
      activity indexes, as well as fecal calprotectin levels in Crohn's disease.

PMID- 30284909
TI  - Apparent diffusion coefficient and enhancement patterns in MR imaging as markers
      of severe or moderate ileum inflammation in Crohn's disease.
AB  - BACKGROUND AND PURPOSE: magnetic resonance enterography has been increasingly
      used for the diagnosis and follow-up of Crohn's disease (CD). The purpose of the
      study was to compare the apparent diffusion coefficient (ADC) with wall
      enhancement for the differentiation of severe, moderate or no inflammation
      activity in the ileum. METHODS: a prospective, blinded study was conducted of 46
      CD patients with a clinical Crohn's disease activity index (CDAI) >= 220 and a
      simple endoscopic score for Crohn's disease (ES-CD) >= 7, which yielded 58
      inflamed segments with CD. Twenty controls were also included. All segments were
      characterized by four ADC readings. The two different enhancement patterns
      observed in inflamed segments, transmural or mucosal, were associated with
      severely (23) or moderately (35) active CD. RESULTS: the ADC value decreased from
      2.79 +/- 0.35 x 10-3 mm2/s for normal segments to 1.81 +/- 0.39 x 10-3 mm2/s for
      the moderately inflamed segments and 1.15 +/- 0.20 x 10-3 mm2/s for severely
      inflamed segments (p <= 0.0001). ROC curve analysis on the basis of the three ADC
      distributions showed a very good discrimination capability with an area under the
      curve of 0.95. Three groups were defined as follows: normal ileum ADC > 2.4 x 10
      3 mm2/s, moderate stages of inflammation 1.5 x 10-3 mm2/s < ADC <= 2.4 x 10-3
      mm2/s and severe stages of ADC <= 1.5 x 10-3 mm2/s. CONCLUSIONS: the ADC value
      reliably discriminates between normal and inflamed ileum and also distinguishes
      between severe and moderate inflammation.

PMID- 30284910
TI  - Delayed gastric emptying following pancreatoduodenectomy: a Roux-en-Y
      gastrojejunostomy vs Billroth II gastrojejunostomy randomized study.
AB  - INTRODUCTION: delayed gastric emptying (DGE) is the most common complication
      after pancreaticoduodenectomy (PD) and it occurs in 50% of cases. OBJECTIVES: the
      endpoint was to determine if there were any differences in the incidence of DGE
      between Roux-en-Y gastrojejunostomy (ReY) and Billroth II gastrojejunostomy (BII)
      in PD with pancreaticogastrostomy (PG). METHODS: this was a case-control
      prospective randomized study of all PD cases between 2013 and 2016. Sixty-four
      patients were included, 32 in each group. An intention-to-treat statistical
      analysis was performed. RESULTS: no significant differences were found with
      regard to morbidity and mortality or hospital stay. DGE was present in 25% of the
      patients in the BII group in comparison to 15.6% in the ReY group, which was not
      statistically significant (p = 0.35). There was a higher percentage of patients
      with primary DGE in the BII group, 12.5% versus 6.2%, but this was not
      statistically significant (p = 0.53). No difference in DGE severity was observed.
      Male gender (OR 8.38 [1.1; 129]), abdominal complications (OR 15 [1.7; 396.9]),
      pre-operative malnutrition (OR 99.7 [3.3, 11,126]) and hemorrhage (OR 9.4 [1.37,
      107.94]) were the main risk factors for DGE according to the multivariate
      analysis. CONCLUSIONS: there were no significant differences in the incidence or
      severity of DGE between BII or ReY after PD with PG.

PMID- 30284911
TI  - Algorithms to facilitate shared decision making for the management of mild-to
      moderate ulcerative colitis.
AB  - INTRODUCTION: Non-adherence has been a key barrier to the efficacy of medical
      treatments in ulcerative colitis (UC). Engaging patients in their IBD care via
      shared decision making (SDM) to facilitate self-management may improve adherence
      to therapy. Areas covered: This review aims to summarize the most recent trial
      evidence from 2012-2017 for mild-to-moderate UC in order to develop clinical
      algorithms that guide SDM to facilitate self-management. A structured literature
      search via multiple electronic databases was performed using the search terms
      'ulcerative colitis,' 'treatment,' 'management,' 'medication,' 'maintenance,'
      'remission,' '5-ASA,' and 'inflammatory bowel disease. Expert commentary: Novel
      formulations of existing oral and topical medications have expanded the treatment
      options available for the induction and maintenance therapy for mild-to-moderate
      UC. Daily dosing of 5-ASA therapy is equivalent to twice daily dosing. The
      combination therapies of oral plus topical 5-ASA therapy and 5-ASA plus
      corticosteroid therapy are more effective than monotherapy. Budesonide MMX now
      plays a role in the management of mild-to-moderate UC. This review collates the
      evidence on drug efficacy and safety, adherence and tolerability, and non
      invasive monitoring of mild-to-moderate UC into SDM-orientated algorithms to
      facilitate self-management.

PMID- 30284912
TI  - Characteristics, diagnoses, illness course and risk profiles of inpatients
      admitted for at least 21 days to an Australian private psychiatric hospital.
AB  - OBJECTIVES: To perform a clinical and risk audit of private hospital inpatients
      staying in hospital at least 21 days. METHODS: Of 492 admissions for >=21 days in
      2016, 40 were randomly selected for audit. Characteristics, illness severity and
      course using the Clinical Global Impression severity (CGI-S) subscale and
      improvement (CGI-I) subscale, and clinical risk profiles were ascertained at
      admission, day 15 and discharge by two psychiatrists. RESULTS: The cases were 65%
      female, age 50.0+/-16.2 years (range 24-86), 43% in relationships, and 28% on
      disability support. The length of stay was 29+/-7 days. On admission 88% were
      severely or markedly ill on the CGI-S subscale. Thirty-nine of 40 cases had >=3
      psychiatric diagnoses: 93% depression, 48% bipolar, 15% schizophrenia. High risk
      was present in suicide risk (48%), illness-induced dysfunction risk (78%) and
      physical risk (28%). By day 15, 63% were not improved or marginally worse.
      Suicide ratings were unimproved. By the time of discharge, illness severity and
      risk ratings were significantly reduced. CONCLUSION: Private hospital inpatients
      staying >=21 days were predominantly female and had severe, diagnostically
      complex illnesses and high risk ratings. Most were still seriously unwell after
      15 days. Patients improved significantly by the time of discharge (though were by
      no means recovered), indicating that the duration of hospitalisation was
      appropriate.

PMID- 30284914
TI  - Australia's 'Better Access' scheme: Has it had an impact on population mental
      health?
AB  - BACKGROUND:: Australia introduced the Better Access scheme in late 2006, which
      resulted in a large increase in the provision of mental health services by
      general practitioners (GPs), clinical psychologists, other psychologists and
      allied health professionals. It is unknown whether this increase in services has
      had an effect on the mental health of the population. METHODS:: The following
      data were examined: per capita use of mental health services provided by GPs,
      clinical psychologists, other psychologists, allied health professionals and
      psychiatrists from 2006 to 2015 according to the Australian Government Department
      of Human Services; prevalence of psychological distress in adults (as measured by
      the K10) from National Health Surveys in 2001, 2004-2005, 2007-2008, 2011-2012
      and 2014-2015; and the annual suicide rate from 2001 to 2015 according to the
      Australian Bureau of Statistics. RESULTS:: The large increase in the use of
      mental health services after the introduction of the Better Access scheme had no
      detectable effect on the prevalence of very high psychological distress or the
      suicide rate. CONCLUSION:: Better Access has not had a detectable effect on the
      mental health of the Australian population.

PMID- 30284913
TI  - Retrospective analysis of effects of sodium-glucose co-transporter 2 inhibitor in
      Japanese type 2 diabetes mellitus patients with chronic kidney disease.
AB  - AIM: The aim of this study was to assess the renal effects of the glucose
      lowering SGLT2 inhibitors in Japanese type 2 diabetes mellitus patients with
      chronic kidney disease. METHODS: The Kanagawa Physicians Association maintains a
      registry of patients who visit their 31 clinics. Clinical data of type 2 diabetes
      mellitus patients with chronic kidney disease, who were prescribed SGLT2
      inhibitors in addition to other treatments, were collected and analysed. RESULTS:
      SGLT2i was associated with a fall in HbA1c from 64.1 +/- 16.7 mmol/mol (8.0 +/-
      1.5%) to 56.5 +/- 12.9 mmol/mol (7.3 +/- 1.2%) ( p < 0.01) in 869 analysed cases,
      a decrease in urine albumin-creatinine ratio from a median of 47.1 to 41.1
      mg/gCr, and decrease in estimated glomerular filtration rate from 77.7 +/- 23.9
      to 75.0 +/- 23.9 mL/min/1.73 m2 ( p < 0.01). The effect on albumin-creatinine
      ratio was independent of age or stage of estimated glomerular filtration;
      however, there was a significant negative correlation between albumin-creatinine
      ratio at the initiation of SGLT2 inhibitor and change in ACR. Multiple linear
      regression analysis identified use of empagliflozin, beta-blockers, and
      sulphonylureas, Deltasystolic blood pressure at office, serum Cr and albumin
      creatinine ratio value at initiation of SGLT2 inhibitor as independent and
      significant determinants of change in ACR. CONCLUSIONS: This study confirmed that
      the beneficial renal effects of SGLT2 inhibitor in Japanese type 2 diabetes
      mellitus patients with chronic kidney disease, similar to those reported in large
      scale clinical trials conducted in Western countries.

PMID- 30284915
TI  - A cost-benefit analysis of the Improving Access to Psychological Therapies
      programme using its key defining outcomes.
AB  - The economic argument underpinning the Improving Access to Psychological Therapy
      programme has been a central component in its initial and continued investment.
      Using open-access data, this article undertook a cost-benefit analysis using the
      programme's key defining outcomes to determine its return-on-investment. It was
      found that in terms of investment and efficiency gains, the programme was in the
      higher ends of the cost spectrum for delivering psychological therapies. Although
      cost-estimates appear promising at first, when set in the context of a lower
      number of treatment contacts and a high proportion of early disengagement,
      estimates increased sharply.

PMID- 30284916
TI  - Antibiotic activity of the antioxidant drink effective Microorganism-X (EM-X)
      extracts against common nosocomial pathogens: an in vitro study.
AB  - EM-X is a mixed consortium of beneficial microorganisms of natural occurrence
      (lactic bacteria, yeast and photosynthetic bacteria). The aim of this study is to
      evaluate the antimicrobial activity in-vitro of EM-X to the principal pathogens
      isolated in clinical settings and to understand if it could be a suitable
      adjuvant to synthetic antibiotics. According the World Health Organization we
      performed antimicrobial assays to the main pathogens usually found in hospital
      wards. After antimicrobial testing, EM-X has been shown to be most effective at a
      concentration of 40 mg/ml four time concentrated than the commercial original
      solution (10 mg/ml). The EM-X antimicrobial action, although effective against
      bacteria, has proved to be ineffective against the candida genus. This active
      range of concentration (mg/ml) may prove a very weak action of EM, but further
      investigations will be done to separate the active substances form the inactive
      ones in this complex mixture.

PMID- 30284917
TI  - Predictors and patterns of portal use in patients with multiple chronic
      conditions.
AB  - Objective To explore predictors of portal use by patients (registered portal
      users) with multiple chronic conditions according to demographic characteristics
      and use of specific features hypothesized to support self-management. Methods Two
      data sources were used in this analysis: electronic health records and 12 months
      of data from web server log files. Patients ( n = 500) included in the analysis
      were 45 years or older, registered portal users, and diagnosed with at least two
      chronic conditions. We fit a negative binomial regression model to predict portal
      use (number of logins) based on practice size and location, demographic
      characteristics, and use of specific portal features (secure messaging and
      patient-entered data). Results Among patients with one or more logins, age,
      distance separating the patient from his or her primary care provider, and having
      a diagnosis of heart failure were significant predictors of portal use ( p <
      .05). No significant differences in portal use were found according to gender,
      ethnicity, or practice size and location. Conclusion Considering the
      extraordinary investment on implementation and meaningful use of portal
      technology, low overall use and the large number of registered non-users is
      especially troubling. Regardless, our results demonstrate potential opportunities
      to leverage portal technology especially for patients living in rural and
      underserved areas to improve self-management of chronic illness.

PMID- 30284918
TI  - The Girl in the Book: a screenplay on child abuse, personality dysfunction and
      recovery - of interest to not only psychiatry.

PMID- 30284919
TI  - Managing difficult and violent adolescents ( adolescents difficiles) in France: a
      genealogical approach.
AB  - 'Difficult adolescent' is a clinical category defined by psychiatrists'
      expertise. Since the end of the 1990s, it has been extensively used to describe a
      population of disruptive, violent yet vulnerable adolescents, at the margins of
      public institutions that manage youth deviancy in France. For the present study,
      an interconnected network of 49 documents was analysed using a genealogical
      method in order to provide comprehensive elements in the results. This category
      found its ecological niche in the 1960s, revealing a moral tension in the use of
      constraint. It addressed new problems of intractable individuals, whose
      dangerousness and vulnerability require coordination between penal, social and
      psychiatric institutions. It defines an ambiguous condition, suspended between
      the trouble experienced by the caregivers and an adolescent's individual
      disorder.

PMID- 30284920
TI  - The longitudinal associations among grandparent-grandchild cohesion, cultural
      beliefs about adversity, and depression in Chinese rural left-behind children.
AB  - This study examined the effects of grandparent-grandchild cohesion on the cross
      lagged associations between depression and cultural beliefs about adversity in a
      sample of 625 rural left-behind children in China. Grandparent-grandchild
      cohesion was concurrently and longitudinally associated with children's
      depression and cultural beliefs about adversity. Cultural beliefs about adversity
      mediated the associations between grandparent-grandchild cohesion and children's
      depression, while depression mediated the associations between grandparent
      grandchild cohesion and children's beliefs about adversity. Left-behind status
      differences were also found in mediation models. These findings suggest the
      important role of grandparent-grandchild cohesion in left-behind children's
      adjustment.

PMID- 30284921
TI  - Identification of Enterococci, Staphylococci, and Enterobacteriaceae from
      Slurries and Air in and around Two Pork Farms.
AB  - In this study, we investigated the airborne dissemination of bacteria from the
      inside of two very different pork farms (an intensively confined farm and an open
      range farm) to the immediate environment. Samples were taken from the slurry,
      from the air inside the farms (area 0), and from their immediate surroundings at
      a distance of 50, 100, and 150 m in four directions (north, south, east, and
      west). A control sample in the air of a zone far away from human or animal
      activity was also taken. Identification of isolates was made by means of the
      matrix-assisted laser desorption-ionization time of flight system. A total of
      1,063 isolates were obtained, of which a mere 7 came from the air of the control
      area. Staphylococci, enterococci, and Enterobacteriaceae were selectively
      targeted for isolation and represented 48.6, 27.2, and 21.6% of the isolates,
      respectively. The species identified from the air of surrounding areas (
      Enterococcus faecalis, Enterococcus hirae, and Staphylococcus arlettae, mainly)
      were also present inside the farms studied. The results suggest that air is
      involved in bacterial dissemination, and pork farms should be considered a
      potential source of foodborne bacteria that might contaminate surrounding areas,
      including vegetable orchards. Wind direction appears as a factor involved in
      bacterial dispersion through the air, but its effect may be conditioned by
      existing vegetation and orographic conditions.

PMID- 30284922
TI  - Presence and Distribution of Histo-Blood Group Antigens in Pacific Oysters and
      the Effects of Exposure to Noroviruses GI.3 and GII.4 on Their Expression.
AB  - Noroviruses (NoVs) are one of the most important foodborne viral pathogens
      worldwide. Oysters are common carriers of NoVs and are responsible for their
      transmission. NoVs recognize human histo-blood group antigens (HBGAs) as
      receptors. Recent studies indicate that HBGA-like molecules also exist in oyster
      tissues and that they may play a key role in the binding of NoVs. However, the
      mechanism by which different genotypes of NoV accumulate in different oyster
      tissues is unknown. In this study, the presence and distribution of different
      types of HBGA-like molecules were evaluated in 240 oysters collected from the
      Shandong Peninsula of People's Republic of China for 1 year. The HBGA-like
      molecules were detected at various rates and expressed at different levels in
      different tissues. Immunohistochemistry confirmed the diversity of HBGA-like
      molecules in four oyster tissues. Eight types of HBGA-like molecules (types A, B,
      H1, Lewis x, Lewis y, Lewis a, Lewis b, and precursor) were assessed in different
      tissues. Of these, the type A HBGA-like molecule was consistently expressed in
      the gills, digestive tissue, and mantle, while types H1 and Lewis b HBGA-like
      molecules were expressed in the digestive tissues. The expression of HBGA-like
      molecules in response to the NoV challenge was investigated. The levels of types
      A, H1, and Lewis x increased significantly in specific oyster tissues after
      exposure to genogroup II, genotype 4 (GII.4) or genogroup I, genotype 3 (GI.3)
      NoV. The real-time reverse transcription PCR assays indicated that GI.3 NoV
      mainly accumulated in the digestive tissues of oysters, whereas GII.4 NoV
      accumulated in the gills, mantle, and digestive tissues. These results provide
      new insights into the mechanism of NoV bioaccumulation in oysters and suggest
      that NoV accumulation in oysters may be related to the expression of HBGA-like
      molecules.

PMID- 30284923
TI  - Infrared multiple photon dissociation of cesium iodide clusters doped with mono-,
      di- and triglycine.
AB  - Charged cesium iodide clusters doped with mono-, di- and triglycine serve as a
      model system for sea salt aerosols containing biological molecules. Here, we
      investigate reactions of these complexes under infrared irradiation, with spectra
      obtained by infrared multiple photon dissociation. The cluster ions are generated
      via electrospray ionization and analyzed in the cell of a Fourier Transform Ion
      Cyclotron Resonance Mass Spectrometer. Depending on the cluster size and peptide
      length, loss of HI or loss of a glycine unit is observed. The experimental
      measurements are supported by quantum chemical calculations. We show that N-H and
      O-H stretching modes dominate the spectrum, with large shifts depending on local
      interactions, namely due to interaction with iodide anions or intramolecular
      hydrogen bonding. Both experiment and theory indicate that several isomers are
      present in the experimental mixture, with different infrared fingerprints as well
      as dissociation pathways.

PMID- 30284924
TI  - INTRATRACHEAL ADMINISTRATION OF MESENCHYMAL STEM-CELL-DERIVED EXTRACELLULAR
      VESICLES REDUCES LUNG INJURY IN A RAT MODEL OF BRONCHOPULMONARY DYSPLASIA.
AB  - Mesenchymal stem cells (MSCs) prevent the onset of bronchopulmonary dysplasia
      (BPD) in animal models, an effect that seems to be mediated by their secreted
      extracellular vesicles (EVs). The aim of this study was to compare the protective
      effects of intratracheally (IT)-administered MSCs vs. MSC-EVs in a hyperoxia
      induced rat model of BPD. At birth, rats were distributed as follows: animals
      raised in ambient air for 2 weeks (n=10); and animals exposed to 60% oxygen for 2
      weeks and treated with IT-administered physiological solution (n=10), MSCs
      (n=10), or MSC-EVs (n=10) on postnatal days 3, 7, and 10. The sham-treated
      hyperoxia-exposed animals showed reductions in total surface area of alveolar air
      spaces, and total number of alveoli (Nalv), and an increased mean alveolar volume
      (Valv). EVs prompted a significant increase in Nalv (P<0.01), and a significant
      decrease in Valv (P<0.05) compared with sham-treated animals, while MSCs only
      significantly improved Nalv (P<0.05). Small pulmonary vessels of the sham-treated
      hyperoxia-exposed rats also showed an increase in medial thickness, which only
      EVs succeeded in preventing significantly (P<0.05). In conclusion, both EVs and
      MSCs reduce hyperoxia-induced damage, with EVs obtaining better results in terms
      of alveolarization and lung vascularization parameters. This suggests that IT
      administered EVs could be an effective approach to BPD treatment.

PMID- 30284926
TI  - IL-10 Producing B Cells Regulate Th1/Th17 Cell Immune Responses in Pneumocystis
      Pneumonia.
AB  - Pneumocystis pneumonia (PCP) is a common opportunistic infectious disease that is
      prevalent in immunosuppressed hosts. Accumulating evidence shows that B cells
      play an important role in infectious diseases. In the present study, the immune
      regulatory role of mature B cells in host defense to Pneumocystis was evaluated.
      Pneumocystis infection resulted in a decrease in B cells in patients and mice,
      and the Pneumocystis burden in B cell-deficient (MUMT) mice also progressively
      increased from weeks 1 to 7 after infection. The clearance of Pneumocystis was
      delayed in BAFF-R-deficient mice (BAFF-R-/- mice), which had few B cells and
      Pneumocystis-specific IgG and IgM antibodies, compared with clearance in wild
      type (WT) mice. There were fewer effector CD4+ T cells and higher percentages of
      Th1/Th17 cells in BAFF-R-/- mice than in WT mice. Adoptive transfer of naive B
      cells, mRNA sequencing, and IL-1beta neutralization experiments indicated that IL
      1beta is a likely determinant of the B10 cell-mediated suppression of Th1/Th17
      cell immune responses in BAFF-R-/- PCP mice. Our data indicated that B cells play
      a vital role in the regulation of T helper cells in response to Pneumocystis
      infection.

PMID- 30284925
TI  - TAILS proteomics reveals dynamic changes in airway proteolysis controlling
      protease activity and innate immunity during COPD exacerbations.
AB  - Dysregulated protease activity is thought to cause parenchymal and airway damage
      in COPD. Multiple proteases have been implicated in COPD and identifying their
      substrates may reveal new disease mechanisms and treatments. However as proteases
      interact with many substrates which may be protease inhibitors or proteases
      themselves, these webs of protease interactions make the wider consequences of
      therapeutically targeting proteases difficult to predict. We therefore used a
      systems approach to determine protease substrates and protease activity in COPD
      airways. Protease substrates were determined by proteomics using Terminal Amine
      Isotopic Labelling of Substrates (TAILS) methodology in paired sputum samples
      during stable COPD and exacerbations. Protease activity and specific protein
      degradation in airway samples were assessed using western blotting, substrate
      assays and ex vivo cleavage assays. 299 proteins were identified in human COPD
      sputum, 125 of which were proteolytically processed including proteases, protease
      inhibitors, mucins, defensins, complement and other innate immune proteins.
      During exacerbations, airway neutrophils and neutrophil proteases increased. More
      proteins were cleaved, particularly at multiple sites, consistent with
      degradation and inactivation. During exacerbations, different substrates were
      processed including protease inhibitors, mucins and complement proteins.
      Exacerbations were associated with increasing airway elastase activity and
      increased processing of specific elastase substrates including secretory
      leukocyte protease inhibitor. Proteolysis regulates multiple processes including
      elastase activity and innate immune proteins in COPD airways and differs during
      stable disease and exacerbations. The complexity of protease, inhibitor and
      substrate networks makes the effect of protease inhibitors hard to predict which
      should be used cautiously.

PMID- 30284927
TI  - Airway smooth muscle photorelaxation via opsin receptor activation.
AB  - Non-visual opsin receptors have recently been implicated in blue light mediated
      photorelaxation of smooth muscle in various organs. Since photorelaxation has not
      yet been demonstrated in airway smooth muscle (ASM) or in human tissues, we
      questioned whether functional opsin receptors are expressed in mouse and human
      ASM. Messenger RNA encoding the opsin 3 receptor was detected in both human and
      mouse airway smooth muscle. To demonstrate the functionality of the opsin
      receptors, we performed wire myography of ex vivo airway smooth muscle from mouse
      and human upper airways. Blue light mediated relaxation of acetylcholine pre
      constricted airways was intensity and wavelength dependent (maximum relaxation at
      430 nm blue light) and was inhibited by blockade of the large conductance calcium
      activated potassium (BK) channels with iberiotoxin. We further implicated opsin
      receptors as key mediators in functional photorelaxation by demonstrating
      increased relaxation in the presence of a G protein receptor kinase 2 (GRK2)
      inhibitor or an opsin chromophore (9-cis-retinal). We corroborated these
      responses in peripheral airways of murine precision cut lung slices. This is the
      first demonstration of photorelaxation in airway smooth muscle via an opsin
      receptor mediated pathway.

PMID- 30284928
TI  - Communication change in ALS: engaging people living with ALS and their partners
      in future research.
AB  - OBJECTIVE: To involve people living with amyotrophic lateral sclerosis (plwALS)
      in the scoping and identification of research priorities related to the changes
      in ALS communication including the use of augmentative and alternative
      communication (AAC). METHODS: Two focus groups of plwALS at early and late stages
      of change to speech intelligibility were carried out as a patient and participant
      involvement exercise. The transcriptions of these groups were analyzed
      thematically and compared between groups. RESULTS: Aspects of anticipation,
      preparation, adaptation and partnership were identified as key to dealing with
      communication change as a result of ALS. In particular the involvement of
      partners was clearly significant, as was the impact on them as well as the
      plwALS. PlwALS successfully contributed to focus groups and the process of group
      discussion about communication itself appeared constructive. CONCLUSIONS:
      Research and new interventions should focus further on how to support the
      partners of plwALS. Future research with plwALS should place AAC strategies and
      technology in the context of wider communication and investigate how best to
      support the anticipation, preparation and adaptation to communication change.
      Specific areas of research need relating to this support are suggested.
      IMPLICATIONS FOR REHABILITATION People living with ALS (plwALS) are rarely
      involved in setting the research agenda in the areas of speech and augmentative
      and alternative communication (AAC). Enabling plwALS to contribute to research,
      even those with no speech, is feasible with appropriate support. Feedback
      indicates that communication change and AAC are experienced in different ways by
      plwALS. Research and intervention should focus on how to support the
      anticipation, preparation and adaptation to communication change for plwALS.

PMID- 30284930
TI  - Joining up the dots.

PMID- 30284929
TI  - Varinostat Alters Gene Expression Profiles in Aortic Tissues from ApoE-/- Mice.
AB  - Atherosclerosis (AS) is a complex, chronic inflammatory disease that is
      characterized by plaque buildup within arterial vessel walls. Preclinical trials
      have suggested that vorinostat, a pan-histone deacetylase inhibitor (HDACi),
      reduces vascular inflammation and AS, but the underlying protective mechanism has
      not been fully elucidated. The present study aimed to identify altered gene
      expression profiles in aortic tissues from ApoE-/- mice after vorinostat
      treatment. Male ApoE-/- mice fed a high-fat diet were treated with either
      vorinostat or vehicle, and the aortic plaque area was quantified 8 weeks after
      treatment. Aortic tissues were collected from both the vorinostat group (n = 3)
      and vehicle group (n = 3) for deep sequencing of the cDNA to construct sRNA
      libraries. Oral administration of vorinostat significantly reduced plaque size in
      the ApoE-/- mice (p < 0.05). In total, 1,550 differentially expressed mRNAs, 56
      differentially expressed miRNAs, and 381 differentially expressed lncRNAs were
      identified in the vorinostat group compared to the vehicle group. Subsequently, a
      global lncRNA-miRNA-mRNA triple network was constructed based on the competitive
      endogenous RNA (ceRNA) theory. The hepatitis C signaling pathway was
      significantly enriched among the differentially expressed mRNAs from the ceRNA
      network, which suggests that vorinostat has anti-inflammatory properties.
      Importantly, the identified target pair of mmu-miR-3075-5p/lncRNA
      A330023F24Rik/Ldlr may regulate drug response. Upregulation of low-density lipid
      receptor (Ldlr) and lncRNA-A330023F24Rik and downregulation of mmu-miR-3075-5p
      were further verified by quantitative real-time polymerase chain reaction. To
      conclude, vorinostat reduced AS in ApoE-/- mice. Differentially expressed mRNA,
      lncRNAs, and miRNAs, as well as their interactions and pathways, were identified,
      which partially explain vorinostat's anti-atherosclerotic effects.

PMID- 30284931
TI  - Mapping a brain.
AB  - Alfie Gleeson and Abigail Sawyer explore the latest advances in high-throughput
      sequencing for neuroscience on the quest to map out the brain. High-throughput
      sequencing technology has enabled research centers across the globe to begin
      mapping neural connections and deciphering neural wiring circuits. From huge
      initiatives in the USA to smaller, but no less important research groups in
      Europe, the quest to map the brain is becoming a worldwide research goal.

PMID- 30284932
TI  - The use of commercially available adhesive tapes to preserve cartilage and bone
      tissue integrity during cryosectioning.
AB  - The use of fluorescent tags to monitor protein expression and to lineage-trace
      cells has become a standard complement to standard histological techniques in the
      fields of embryology, pathology and regenerative medicine. Unfortunately,
      traditional paraffin embedding protocols can substantially diminish or abolish
      the native emission signal of the fluorophore of interest. To preserve the
      fluorescent signal, an alternative is to use cryosectioning; however, this can
      often result in undesirable artefacts such as tearing or shattering -
      particularly for mineralized tissues such as bone and cartilage. Here we present
      a method of using a commercially available tape to stabilize murine femur tissue,
      thus allowing for cryosectioning of cartilage and bone tissues carrying
      fluorescent tags without the need for demineralization.

PMID- 30284933
TI  - Introducing graphical and video abstracts.

PMID- 30284934
TI  - T-blocker: a simple and robust probe-free quantitative PCR assay to detect
      somatic mutations down to 0.1% frequency.
AB  - We have developed a simple and robust probe-free quantitative PCR (qPCR) assay
      method that can detect minor mutant alleles with a frequency as low as 0.1% in a
      heterogeneous sample by introducing a novel T-blocker concept to the allele
      specific PCR method. Four new KRAS and BRAF mutation detection assays were
      developed and their performance was demonstrated by testing a large number of
      replicates, utilizing a customized PCR protocol. Highly efficient and specific
      mutant amplification in conjunction with selective wild-type suppression by the T
      blocker concept enabled 0.1% detection sensitivity using the intercalating dye
      based qPCR chemistry instead of more complex target-specific dye-labeled probes.
      Excellent consistency in sensitivity and specificity of the T-blocker assay
      concept was demonstrated.

PMID- 30284935
TI  - Directional high-throughput sequencing of RNAs without gene-specific primers.
AB  - Ribosomal RNA analysis is a useful tool for characterization of microbial
      communities. However, the lack of broad-range primers has hampered the
      simultaneous analysis of eukaryotic and prokaryotic members by amplicon
      sequencing. We present a complete workflow for directional, primer-independent
      sequencing of size-selected small subunit ribosomal RNA fragments. The library
      preparation protocol includes gel extraction of the target RNA, ligation of an
      RNA oligo to the 5'-end of the target, and cDNA synthesis with a tailed random
      hexamer primer and further barcoding. The sequencing results of a phytoplankton
      mock community showed a highly similar profile to the biomass indicators. This
      method has universal potential for microbiome studies, and is compatible for the
      5'-end sequencing of other RNA types with minimum library preparation costs.

PMID- 30284936
TI  - Potential of circulating biomarkers in liquid biopsy diagnostics.

PMID- 30284937
TI  - Robust evaluation of intermolecular FRET using a large Stokes shift fluorophore
      as a donor.
AB  - Fluorescence (or Forster) resonance energy transfer (FRET) is a straightforward
      and sensitive technique to evaluate molecular interactions. However, most of the
      popular FRET pairs suffer cross-excitation of the acceptor, which could lead to
      false positives. To overcome this problem, we selected a large Stokes shift (LSS)
      fluorophore as a FRET donor. As a successful example, we employed a new FRET pair
      mAmetrine (an LSS yellow fluorescence protein)/DY-547 (a cyanine derivative) to
      substitute CFP/fluorescein that we previously employed to study molecular
      interactions between cyclic nucleotide-binding domains and cyclic nucleotides.
      The new FRET pair is practically free of cross-excitation of the acceptor.
      Namely, a change in the fluorescence spectral shape implies evidence of FRET
      without other control experiments.

PMID- 30284938
TI  - Isolation of spheroid-forming single cells from gastric cancer cell lines:
      enrichment of cancer stem-like cells.
AB  - Isolation of spheroid-forming cells is important to investigate cancer stem cell
      (CSC) characteristics. However, conventional tumor spheroid culture methods have
      not proven suitable because the aggregated spheroids generally maintain their
      original heterogeneity and harbor multiple cells with various characteristics.
      Here we cultured spheroids using a polydimethylsiloxane microwell-based method
      and a limiting dilution protocol. We then isolated and enriched for CSCs that
      formed single cell-derived spheroids from gastric cancer cell lines. Cells from
      the microwell demonstrated higher self-renewal, increased expression of stem cell
      markers and resistance to apoptosis compared with spheroid cells made by the
      traditional method. This novel approach allows efficient cancer stem cell
      isolation and represents a step forward in cancer stem cell studies.

PMID- 30284939
TI  - Mammalian cell culture density determination using a laser through-beam sensor.
AB  - High-throughput protein expression platforms are increasingly used to produce
      proteins for many applications: to support studies in structure/function,
      regulation and proteomics, as well as for direct use as potential biotherapeutic
      agents for medical applications. Here we describe a device that we refer to as
      the flask density reader (FDR) consisting of a through-beam laser and sensor, and
      a customized culture flask-receiving nest. The FDR has been integrated onto GNF
      SystemTM's automated protein expression platform to enable rapid, noninvasive,
      fully automated spectrophotometric determination of cell densities in suspension
      mammalian cell cultures. The FDR reduces the risk of culture contamination from
      frequent flask sampling and greatly reduces the time and effort needed to count
      cells using off-line methods.

PMID- 30284940
TI  - Prepregnancy Factors Are Associated with Development of Hypertension Later in
      Life in Women with Pre-Eclampsia.
AB  - BACKGROUND: The aim of our study was to investigate the prepregnancy
      characteristics that are risk factors for the development of hypertension (HTN)
      and identify prepregnancy factors for the development of HTN in women affected by
      pre-eclampsia in their first pregnancy. METHODS: We enrolled 1910 women who had
      undergone a National Health Screening Examination through the National Health
      Insurance Corporation between 2002 and 2003, and who had their first delivery
      affected by pre-eclampsia in 2004. Women were classified as having HTN if they
      were newly diagnosed with HTN from 2005 through 2012. RESULTS: After 8 years of
      follow-up, 7.7% (148/1910) of pre-eclamptic women developed HTN. Using the Cox
      proportional hazards model, old age (hazard ratio [HR] 3.92, 95% confidence
      interval [CI] 2.47-6.23), a family history of HTN (HR 2.28, 95% CI 1.46-3.58),
      prepregnancy obesity (HR 3.74, 95% CI 2.50-5.59), and high blood pressure (BP)
      (HR 2.78, 95% CI 1.85-4.19) were independently associated with the development of
      HTN. CONCLUSIONS: The results show that the development of HTN in pre-eclamptic
      women is related to prepregnancy factors. Recognizing who subsequently develops
      HTN postpartum in pre-eclamptic women with these prepregnancy factors could lead
      to early identification and lifestyle interventions, which could reduce the
      burden of cardiovascular disease.

PMID- 30284941
TI  - In vitro investigation into the forces involved during lipofilling.
AB  - Breast augmentation using implants is the most common aesthetic and
      reconstructive breast surgical procedure. Complications such as implant rupture
      maybe related to surgical technique and damage to the implant. Autologous fat
      transfer (lipofilling) using metallic cannulae has become a standard adjunctive,
      yet there is little evidence on lipofilling safety in the presence of implants.
      The aims of this study are to verify the effects of different cannulae and to
      quantify the forces applied by surgeons during lipofilling. Silicone gel-filled
      textured implants (200 mL), mounted on a specially constructed mould were
      ruptured with two different cannulae: type A (hole at tip: sharp) and type B
      (hole away from tip: blunt), driven at three speeds (10, 100 and 1000 mm/min),
      and the force at rupture was recorded. In addition, the maximum 10 forces over a
      30-s period applied by 11 plastic surgeons against a breast implant in an in
      vitro environment were recorded using a load cell attached to a type-A cannula.
      Statistical analysis of comparative results was performed using t-tests, with p <
      0.05 considered significant. Results showed that the implant ruptured at forces
      up to 25% lower when cannula A was used compared to cannula B. This supports
      current technique in lipofilling in the use of a blunt tipped cannula. There was
      a significant difference between some displacement rates only, due to the
      viscoelastic nature of the material. The tactile force that surgeons use during
      lipofilling was modelled in vitro and showed a range of maximum forces between
      0.23 and 16.8 N, with a mean maximum value of 6.9 N. Limitation of this study is
      that it may not reflect in vivo behaviour of breast implants. More studies are
      needed to confirm the safety of breast lipofilling in the presence of implants
      using these data as a starting point.

PMID- 30284942
TI  - A role for traditional doctors in health promotion: experience from a trial of
      HIV prevention in Botswana.
AB  - Traditional doctors have been largely ignored in HIV prevention, particularly
      primary prevention. As part of a structural intervention programme to reduce HIV
      risk among young women in Botswana, we trained 147 traditional doctors in four
      districts as well as government health education assistants (HEAs) and teachers
      to run discussion groups in the community and schools, using an evidence-based
      eight-episode audio-drama, covering gender roles, gender violence, and how these
      are related to HIV risk. One year later, we contacted 43 of the 87 trained
      traditional doctors in two districts. Most (32) were running discussion groups
      with men and women, with links to the local HEAs and teachers. They were adept at
      recruiting men to their groups, often a challenge with community interventions,
      and reported positive changes in attitudes and behaviour of group participants.
      Traditional doctors can play an important role in primary prevention of gender
      violence and HIV.

PMID- 30284944
TI  - OUTCOMES OF SNARE-RELATED INJURIES TO ENDANGERED MOUNTAIN GORILLAS ( GORILLA
      BERINGEI BERINGEI) IN RWANDA.
AB  - Mountain gorillas ( Gorilla beringei beringei) are one of the most critically
      endangered great apes in the world. The most common cause of mountain gorilla
      morbidity and mortality is trauma (e.g., injury from conspecifics or snare
      entrapment). We conducted a retrospective case-control study of free-ranging,
      human-habituated mountain gorillas to evaluate factors associated with snare
      entrapment and the results of clinical intervention. Data were collected from
      clinical records on all clinical intervention cases ( n=132) in Volcanoes
      National Park, Rwanda, conducted between 1995-2015. Gorilla doctors treated 37
      gorillas entrapped in snares and 95 gorillas for other clinical conditions
      (including trauma and respiratory illness). Multivariate statistical analyses
      revealed that young gorillas (<8 yr old) were more likely than older gorillas to
      become snared; that comorbidities delayed times to intervention (>=3 d); and that
      severity of wounds at the time of intervention were associated with increased
      risk of lasting impairment (including loss of limb or limb function, or death)
      within 1 mo after intervention. Our results may influence decisions for gorilla
      health monitoring and treatment to most effectively conserve this critically
      endangered species.

PMID- 30284945
TI  - Dichotomous Locomotor Recoveries Are Predicted by Acute Changes in Segmental
      Blood Flow after Thoracic Spinal Contusion Injuries in Pigs.
AB  - Neuroimaging facilitates the translation of animal pre-clinical research to human
      application. The large porcine spinal cord is useful for testing invasive
      interventions. Ideally, the safety and efficacy of a delayed intervention is
      tested in pigs that have recovered sufficiently after spinal cord injury (SCI) to
      allow either deterioration or improvement of function to be detected. We set out
      to create moderate severity T9 injuries in Yucatan minipigs by conducting a
      bridging study adapting methods previously developed in infant piglets. The
      injury severity was varied according to two pneumatic impactor parameters: the
      piston compression depth into tissue or the velocity. To stratify locomotor
      recovery, a 10-point scale used in prior piglet studies was redefined through
      longitudinal observations of spontaneous recovery. Using hindlimb body weight
      support to discriminate injury severity, we found that end-point recovery was
      strongly bimodal to either non-weight-bearing plegia with reciprocating leg
      movements (<5/10) or recovery of weight bearing that improved toward a ceiling
      effect (>= 8/10). No intermediate recovery animals were observed at 2 months post
      injury. The ability of intra-operative ultrasound and acute magnetic resonance
      imaging (MRI) to provide immediate predictive feedback regarding tissue and
      vascular changes following SCI was assessed. There was an inverse association
      between locomotor outcome and early gray matter hemorrhage on MRI and ultrasound.
      Epicenter blood flow following contusion predicted recovery or non-recovery of
      weight-bearing. The depth of the dorsal cerebrospinal fluid space, which varied
      between animals, influenced injury severity and confounded the results in this
      fixed-stroke paradigm.

PMID- 30284947
TI  - Biological and Genomic Characterization of a Novel Tobamovirus Infecting Hoya
      spp.
AB  - Foliar symptoms suggestive of virus infection were observed on the ornamental
      plant hoya (Hoya spp.; commonly known as waxflower) in Florida. An agent that
      reacted with commercially available tobamovirus detection reagents was
      mechanically transmitted to Chenopodium quinoa and Nicotiana benthamiana. Rod
      shaped particles ~300 nm in length and typical of tobamoviruses were observed in
      partially purified virion preparations by electron microscopy. An experimental
      host range was determined by mechanical inoculation with virions, and systemic
      infections were observed in plants in the Asclepiadaceae, Apocynaceae, and
      Solanaceae families. Some species in the Solanaceae and Chenopodiaceae families
      allowed virus replication only in inoculated leaves, and were thus only local
      hosts for the virus. Tested plants in the Amaranthaceae, Apiaceae, Brassicaceae,
      Cucurbitaceae, Fabaceae, and Malvaceae did not support either local or systemic
      virus infection. The complete genome for the virus was sequenced and shown to
      have a typical tobamovirus organization. Comparisons of genome nucleotide
      sequence and individual gene deduced amino acid sequences indicate that it is a
      novel tobamovirus sharing the highest level of sequence identity with
      Streptocarpus flower break virus and members of the Brassicaceae-infecting
      subgroup of tobamoviruses. The virus, for which the name Hoya chlorotic spot
      virus (HoCSV) is proposed, was detected in multiple hoya plants from different
      locations in Florida.

PMID- 30284946
TI  - Autistic Traits in the Neurotypical Population do not Predict Increased Response
      Conservativeness in Perceptual Decision Making.
AB  - Recent research has shown that adults and children with autism spectrum disorders
      have a more conservative decision criterion in perceptual decision making
      compared to neurotypical individuals, meaning that autistic participants
      prioritise accuracy over speed of a decision. Here, we test whether autistic
      traits in the neurotypical population correlate with increased response
      conservativeness. We employed three different tasks; for two tasks we recruited
      participants from China ( N = 39) and for one task from the United Kingdom ( N =
      37). Our results show that autistic traits in the neurotypical population do not
      predict variation in response criterion. We also failed to replicate previous
      work showing a relationship between autistic traits and sensitivity to coherent
      motion and static orientation. Following the argument proposed by Gregory and
      Plaisted-Grant, we discuss why perceptual differences between autistic and
      neurotypical participants do not necessarily predict perceptual differences
      between neurotypical participants with high and low autistic traits.

PMID- 30284948
TI  - Mycoplasmosis of House Finches ( Haemorhous mexicanus) and California Scrub-Jays
      ( Aphelocoma californica) in a Wildlife Rehabilitation Facility with Probable
      Nosocomial Transmission.
AB  - We describe an investigation of an outbreak of conjunctivitis in juvenile House
      Finches ( Haemorhous mexicanus) and California Scrub-jays ( Aphelocoma
      californica) at a central California wildlife rehabilitation facility. In late
      May 2015, the facility began admitting juvenile finches, the majority with normal
      eyes at intake. In June, with juvenile finches already present, the facility
      admitted additional juvenile scrub-jays, again all with normal eyes at intake. In
      July, after conjunctivitis was observed in increasing numbers of juvenile finches
      and scrub-jays, carcasses were submitted for postmortem examination.
      Histopathology of five finches and three scrub-jays identified lymphocytic
      infiltrates in the ocular tissues. Conjunctival swabs from 87% (13/15) finches
      and 33% (4/12) scrub-jays were PCR-positive for Mycoplasma gallisepticum. One
      finch and two scrub-jays were PCR-positive for Mycoplasma synoviae. Additionally,
      gene sequencing (16S rRNA and 16S-23S intergenic spacer region) identified
      Mycoplasma sturni from 33% (3/9) scrub-jays. This outbreak of conjunctivitis
      suggested that M. gallisepticum-infected juvenile finches admitted to and
      maintained in a multispecies nursery likely resulted in transmission within the
      facility to healthy juvenile finches and scrub-jays. Evidence of other Mycoplasma
      spp. in finches and scrub-jays indicates that these species are susceptible to
      infection and may act as carriers. This outbreak highlighted the need for
      effective triage and biosecurity measures within wildlife rehabilitation
      facilities.

PMID- 30284949
TI  - In vivo conversion of astrocytes to oligodendrocyte lineage cells using
      chemicals: targeting gliosis for myelin repair.
AB  - AIM: It would be clinically ideal to target astrocytes in vivo for conversion
      into oligodendrocyte lineage cells to reduce astrogliosis and generate new
      myelinating cells. MATERIALS & METHODS: Here, we prepared a GFP-labeled human
      astrocyte cell line, treated with epigenetic modifiers trichostatin A or 5
      azacytidine and transplanted them into cuprizone-induced demyelinated mice
      brains. The fate of the transplanted astrocytes was studied at days 7, 14 and 28
      post-transplantation. RESULTS: GFP+ astrocytes were reduced over time, whereas
      the GFP+ oligodendrocyte lineage cells were found on days 14 and 28. Nontreated
      astrocytes did not convert to myelinating cells following transplantation. Cell
      conversion was proved in vitro by maintaining the treated cells in
      oligodendrocyte progenitor cell medium. CONCLUSION: These findings seem promising
      for the application of epigenetic modifiers, especially their targeted delivery
      to glial scars to treat demyelinating diseases.

PMID- 30284950
TI  - Advance care planning in community dwellers: A constructivist grounded theory
      study of values, preferences and conflicts.
AB  - BACKGROUND: Most laypeople have not engaged in any advance care planning. Yet
      they are expected to articulate choices for life-sustaining interventions when
      they need admission to an acute care hospital in Canada. AIM: To describe how
      laypeople understand and make decisions for life-sustaining interventions when
      engaging in advance care planning. DESIGN: Semi-structured interviews using
      constructivist grounded theory methodology and purposive sampling. SETTING: Mid
      size Canadian urban community Participants: In total, 20 healthy laypeople, 55
      years and older, participated in in-depth semi-structured face-to-face
      interviews. Theoretical sampling was used to explore findings from the first
      round of interviews. Ten participants were invited for repeat interviews.
      RESULTS: Four major themes were identified. Most participants claimed at the
      outset that they had engaged in advance care planning, but they were unfamiliar
      with contemporary life-sustaining interventions and had not factored these into
      their decisions. Participants' confidence in their substitute decision makers
      precluded them from having explicit discussions with these individuals.
      Participants expressed their values and preferences in terms of unacceptable
      functional outcomes from serious illness, rather than desired interventions. The
      process of articulating their preferences within the interviews was subject to
      decision conflicts, which in turn helped them re-evaluate and refine their
      decisions. CONCLUSION: Advance care planning for the healthy older adult is
      challenging. Meaningful engagement may lead to conflicts in decision-making.
      Efforts to improve engagement must reflect what patients know and understand,
      their focus on unacceptable negative outcomes rather than interventions, and the
      need for iterative discussions with health-care providers.

PMID- 30284951
TI  - GENETIC RELATEDNESS OF EPIZOOTIC HEMORRHAGIC DISEASE VIRUS SEROTYPE 2 FROM 2012
      OUTBREAK IN THE USA.
AB  - During summer and early fall of 2012, the US experienced the largest outbreak of
      hemorrhagic disease (HD) on record; deer (both Odocoileus virginianus and
      Odocoileus hemionus) in 35 states were affected, including many northern states
      where HD typically does not occur. Epizootic hemorrhagic disease virus (EHDV) was
      the predominant virus isolated, with serotype 2 (EHDV-2) representing 66%
      (135/205) of all isolated viruses. Viruses within the EHDV serogroup are
      genetically similar, but we hypothesized that subtle genetic distinctions between
      viruses would exist across the geographic range of the outbreak if multiple EHDV
      2 strains were responsible. We examined viral relatedness and molecular
      epidemiology of the outbreak by sequencing the mammalian binding protein (VP2)
      gene and the insect vector binding protein (VP7) gene of 34 EHDV-2 isolates from
      2012 across 21 states. Nucleotide sequences of VP2 had 99.0% pairwise identity;
      VP7 nucleotide sequences had 99.1% pairwise identity. Very few changes were
      observed in either protein at the amino acid level. Despite the high genetic
      similarity between isolates, subtle nucleotide differences existed. Both VP2 and
      VP7 gene sequences separated into two distinct clades based on patterns of single
      nucleotide polymorphisms after phylogenetic analysis. The clades were divided
      geographically into eastern and western clades, although those divisions were not
      identical between VP2 and VP7. There was also an association between percent
      sequence identity and geographic distance between isolates. We concluded that
      multiple EHDV-2 strains contributed to this outbreak.

PMID- 30284952
TI  - Can the use of proprioceptive knee braces have implications in the management of
      osteoarthritic knees: An exploratory study.
AB  - BACKGROUND: Use of proprioceptive knee braces to control symptomology by altering
      neuromuscular control mechanisms has been shown in patellofemoral pain. Although
      their potential in patients with knee osteoarthritis is vast, little research has
      examined their efficacy. OBJECTIVES: This study examines the effect of a
      proprioceptive knee brace on lower limb kinematics and kinetics in healthy
      participants and in participants with OA. METHODS: Thirteen healthy participants
      were asked to perform a 10-cm step-down task with and without a proprioceptive
      brace. Data were collected using a 10-camera Qualisys system. Individuals with
      osteoarthritis completed the Knee injury and Osteoarthritis Outcome Score before
      and after 4 weeks of intervention. RESULTS: During step-down reductions in knee
      maximum internal rotation, transverse range of movement, transverse plane angular
      velocity and maximum internal rotation angular velocity was seen. Ankle plantar
      flexion and inversion angular velocity decreased while inversion and maximum
      supination angular velocity increased. Improvements in Knee injury and
      Osteoarthritis Outcome Score were noted across all parameters with brace use.
      CONCLUSION: Positive changes in kinematic variables in multiple planes can be
      achieved with proprioceptive bracing alongside improved patient outcome. These
      changes occur at the knee but analysis of other weight bearing joints should not
      be overlooked in future studies. This study supports the concept of neuromuscular
      reinforcement and re-education through proprioceptive bracing and its application
      in the management in knee osteoarthritis. Clinical relevance Proprioception can
      alter symptoms and biomechanics embraced and adjacent lower limb joints. The
      results of this study highlights the potential uses of non-mechanical bracing in
      the treatment of osteoarthritis and other potential to bridge the osteoarthritis
      treatment gap. Furthermore, large-scale research is needed to match disease
      subset to brace type.

PMID- 30284953
TI  - Candidatus Liberibacter asiaticus and its vector, Diaphorina citri, augments the
      TCA cycle of their host via the GABA shunt and polyamines pathway.
AB  - Huanglongbing, a destructive citrus disease, is associated with Candidatus
      Liberibacter asiaticus (CLas), which is transmitted by the Asian citrus psyllid,
      Diaphorina citri. Both CLas and its vector manipulate the host metabolism for
      their benefit to meet their nutritional needs and neutralize the host defense
      responses. We used a targeted GC-MS-based method to explore the connection
      between TCA cycle, gamma-aminobutyric acid (GABA)-shunt and polyamines (PAs)
      pathways in citrus. CLas and D. citri accelerated the conversion of alpha
      ketoglutarate to glutamate, then to GABA, causing an accumulation of GABA in the
      cytosol. In silico analysis showed that citrus genome possesses a putative GABA
      permease that connects the GABA-shunt with TCA cycle and supports the
      accumulation of succinate, fumarate, and citrate. Additionally, the PAs
      biosynthetic pathway might be connected directly to the TCA cycle through the
      production of fumarate, or indirectly via enhancement of GABA-shunt. Taken
      together, we suggest that GABA-shunt and PAs pathway are alternative pathways
      that contribute to the flux towards succinate rather than an intact TCA cycle in
      citrus. Both CLas and its vector enhance these pathways. This study provides more
      insights into citrus responses to the HLB pathosystem, and could be a further
      step to providing clues for understanding the nutritional needs of CLas, which
      could help in culturing CLas.

PMID- 30284954
TI  - Platelet-rich plasma lyophilization enables growth factor preservation and
      functionality when compared with fresh platelet-rich plasma.
AB  - AIMS: To compare levels and activity of the growth factors between fresh and
      lyophilized platelet-rich plasma (PRP). METHODS: Analysis of platelet
      concentration using fibroblast and human umbilical vein endothelial cell cultures
      were compared between fresh and lyophilized PRP obtained from peripheral blood.
      RESULTS: After lyophilization, 54% of platelets were intact whereas the fresh
      showed no aggregation with agonists (levels under 20%). The concentration of
      growth factors (VEGF, EGF, TGF-beta and PDGF) in both products were similar.
      Fresh and lyophilized PRPs induced proliferation in the fibroblasts at 24 h
      (0.303 vs 0.300, respectively). CONCLUSION: Lyophilized PRP appears to be an
      alternative to fresh PRP and the results evidenced the role of growth factors as
      a key element in the activity of this product.

PMID- 30284955
TI  - Successful treatment of high-grade vulval intra-epithelial neoplasia with
      imiquimod 5% in a renal transplant recipient.
AB  - Organ transplant recipients are at a higher risk of pre-malignant human
      papillomavirus-associated lesions due to immunosuppression. The efficacy of
      immunomodulants such as imiquimod 5% is not yet fully evaluated in this
      population. We describe a case of vulval intra-epithelial neoplasia in a renal
      transplant recipient which was successfully treated with topical imiquimod.

PMID- 30284956
TI  - The first mite: insect genealogy in Hooke's Micrographia.
AB  - What happens when you take the idea of the biblical Adam-the first human - and
      apply it to insects? You create an origin story for Nature's tiniest creatures,
      one that gives them 'a Pedigree as ancient as the first creation'. This the
      naturalist Robert Hooke argued in his treatise, the Micrographia (1665). In what
      follows, I will retrace how Hooke endeavoured to show that insects-then widely
      believed to have arisen out of the dirt - were the products of an ancient
      lineage. These genealogies, while constructed from empirical observation, were
      conjectures of the imagination. Section 2 shows how Hooke introduced the concept
      of a 'prime parent' (an Adam-insect) to explain the anatomical similarities
      between 'mites'. Section 3 demonstrates how Hooke defined the family of "gnats"
      as tiny machines built from the same components and relates Hookean genealogies
      to contemporary ideas about Noah's Ark. Section 4 shows how Hooke outlined the
      morphology of 'insects' (delineating what we now call arthropods). Section 5
      explores how Hooke used fossils to study these animals in the distant past. In
      sum, Hooke was turning natural history - collecting and describing insects - into
      natural history: reconstructing their origins.

PMID- 30284957
TI  - Proteomics investigation of the changes in serum proteins after high- and low
      flux hemodialysis.
AB  - PURPOSE: This study aimed to use proteomics methods to investigate the changes in
      serum protein levels after high- and low-flux hemodialysis (HD). METHODS: Before
      and after HD, serum samples were obtained from two selected patients who were
      treated with a Polyflux 140 H high-flux dialyzer and a Polyflux 14 L low-flux
      dialyzer during two continuous therapy sessions. Liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) was performed to identify the proteins. RESULTS: A
      total of 212 and 203 serum proteins were identified after high-flux and low-flux
      HD, respectively. After high-flux HD, 21 proteins increased, and 132 proteins
      decreased. After low-flux HD, 87 proteins increased, and 45 proteins decreased.
      High-flux HD led to a significantly greater reduction in protein levels than low
      flux HD (0.73 +/- 0.13 vs. 0.84 +/- 0.18, p = .00). Among the increased and
      decreased proteins, the isoelectric point (pI) values mainly ranged from 5 to 7,
      and the molecular weights (Mws) were mostly smaller than 30 kDa. The serum
      proteins showed no difference in pI or Mw for high- and low-flux HD. Gene
      ontology (GO) analysis showed that the detected proteins were related to immune
      system processes and complement activation. CONCLUSIONS: Serum protein levels
      differentially changed after high- and low-flux HD. Long-term effects should be
      observed in future studies.

PMID- 30284959
TI  - Altered amniotic fluid levels of hyaluronic acid in fetal rats with
      myelomeningocele: understanding spinal cord injury.
AB  - Myelomeningocele (MMC) is a devastating congenital neural tube defect, which
      results in the exposure of spinal cord to the intrauterine environment leading to
      secondary spinal cord injury and severe impairment. Though, the mechanisms
      underlying the secondary pathogenesis are clinically relevant, the exact cause of
      in utero acquired spinal cord damage remains unclear. The objective of this study
      was to determine whether the Hyaluronic acid (HA) concentration in amniotic fluid
      (AF) in the retinoic acid-induced model of MMC is different from that in normal
      controls and whether these differences could have an impact on the viscosity of
      AF. Our data shows that the concentration of HA in AF samples from fetuses with
      MMC (MMC-AF) and normal control samples (Norm-AF) were not significantly
      different at embryonic day 18 (E18) and E20. Thereafter, the HA concentration
      significantly increased in Norm-AF but not in MMC-AF. Compared with Norm-AF, the
      concentration of HA in MMC-AF and the viscosity of MMC-AF were significantly
      lower at E21. Agarose gel electrophoresis confirmed a significant reduction in
      the HA level of MMC-AF compared to Norm-AF at E21. No HA degrading activity was
      detected in MMC-AF. In summary, we identified a deficiency in the AF level of HA
      and the viscosity of AF in fetal rats with MMC. This data is discussed in
      relation to a potential role the reduction in the AF viscosity due to the low
      level of HA may play in the exacerbating effects of mechanical trauma on spinal
      cord damage at the MMC lesion site.

PMID- 30284958
TI  - Production of Tissue-Engineered Small Intestine in Rats with Different Ages of
      Cell Donors.
AB  - IMPACT STATEMENT: This study compared side-by-side the impact of donor age on the
      production of tissue-engineered small intestine (TESI). Each age represents a
      specific period of life: E18 for fetuses, 5-day-old pups for neonates, 21-day-old
      rats for weanlings, and 6-week-old rats for adults. The TESI produced was
      compared macroscopically and microscopically. The mechanism(s) contributing to
      the differences observed was explored by detecting proliferating cells in the
      TESI and by analyzing intestinal stem cell gene expression in donor cells. These
      data may provide valuable information for future application of TESI clinically.

PMID- 30284960
TI  - Plastic bag usage in a taxed environment: Investigation on the deterrent nature
      of plastic levy in Maun, Botswana.
AB  - Following the discovery of diamonds in Botswana, there was widespread use of
      plastic bags, possibly as a positive reaction to the change in economic and
      financial landscape of the country. The excessive use of plastic bags by
      consumers throughout Botswana, however, imposed several negative externalities to
      the environment and consequently to livelihoods through their effects on wildlife
      and livestock. The government of Botswana, in an effort to mitigate the negative
      impacts of plastic bags on the environment, introduced both a ban of plastics
      with less than minimum thickness and a plastic bag levy. This study assesses if
      the plastic bag levy regulation by the government is achieving its goal of
      reducing the use of plastic bags in Botswana, where Maun is used as a case study.
      It analyses consumers' perceptions about the plastic levy and its effects on
      their consumption. A total of 154 semi-structured questionnaires were
      administered through random selections of respondents at two shopping malls in
      Maun. In conclusion, the study established that although the levy is well
      targeted on consumers as sources of plastic bag litter, the levy is yet to attain
      its intended purpose of effecting a reduction of plastic bags demanded and/or
      consumed in Maun.

PMID- 30284961
TI  - Australian Clinical Consensus Guideline: The diagnosis and acute management of
      childhood stroke.
AB  - Stroke is among the top 10 causes of death in children and survivors carry
      resulting disabilities for decades, at substantial cost to themselves and their
      families. Children are not currently able to access reperfusion therapies, due to
      limited evidence supporting safety and efficacy and long diagnostic delays. The
      Australian Clinical Consensus Guideline for the Diagnosis and Acute Management of
      Childhood Stroke was developed to minimize unwarranted variations in care and
      document best evidence on the risk factors, etiologies, and conditions mimicking
      stroke that differ from adults. Clinical questions were formulated to inform
      systematic database searches from 2007 to 2017, limited to English and pediatric
      studies. SIGN methodology and the National Health and Medical Research Council
      system were used to screen and classify the evidence. The Grades of
      Recommendation, Assessment, Development, and Evaluation system (GRADE) was used
      to grade evidence as strong or weak. The Guideline provides more than 60 evidence
      based recommendations to assist prehospital and acute care clinicians in the
      rapid identification of childhood stroke, choice of initial investigation, to
      confirm diagnosis, determine etiology, selection of the most appropriate
      interventions to salvage brain at risk, and prevent recurrence. Recommendations
      include advice regarding the management of intracranial pressure and congenital
      heart disease. Implementation of the Guideline will require reorganization of
      prehospital and emergency care systems, including the development of regional
      stroke networks, pediatric Code Stroke, rapid magnetic resonance imaging and
      accreditation of primary pediatric stroke centers with the capacity to offer
      reperfusion therapies. The Guideline will allow auditing to benchmark timelines
      of care, access to acute interventions, and outcomes. It will also facilitate the
      development of an Australian childhood stroke registry, with data linkage to
      international registries, to allow for accurate data collection on stroke
      incidence, treatment, and outcomes.

PMID- 30284962
TI  - Removal of acenaphthene from wastewater by Pseudomonas sp. in anaerobic
      conditions: the effects of extra and intracellular substances.
AB  - Sorption and degradation are considered two primary modes of pollutant removal by
      microorganisms, and extracellular polymeric substances (EPS) have been shown to
      play an important role in these biological processes. However, their role in
      removing refractory organic pollutants the effects of intracellular substances in
      microorganisms remain unclear. In this study, we investigated both the removal
      mechanism and intracellular substances involved in removing the pollutant
      acenaphthene (ACE) from Pseudomonas sp. bacteria in anaerobic conditions. The
      results indicated that the ACE was mainly adsorbed rather than degraded by
      bacteria. Moreover, ACE had little impact on EPS secretion at concentrations
      ranging 0-3 mg/L. Cell walls and membranes accounted for more than 70% of ACE
      adsorption, whereas intra-cellular substances accounted for about 10-25% and the
      effect of other components on ACE adsorption was not obvious. A possible
      mechanism of ACE removal by bacteria is proposed.

PMID- 30284963
TI  - RECENT CHANGES IN INFECTIOUS DISEASES IN EUROPEAN WILDLIFE.
AB  - Many infectious diseases originating from, or carried by, wildlife affect
      wildlife conservation and biodiversity, livestock health, or human health. We
      provide an update on changes in the epidemiology of 25 selected infectious,
      wildlife-related diseases in Europe (from 2010-16) that had an impact, or may
      have a future impact, on the health of wildlife, livestock, and humans. These
      pathogens were selected based on their: 1) identification in recent Europe-wide
      projects as important surveillance targets, 2) inclusion in European Union
      legislation as pathogens requiring obligatory surveillance, 3) presence in recent
      literature on wildlife-related diseases in Europe since 2010, 4) inclusion in key
      pathogen lists released by the Office International des Epizooties, 5)
      identification in conference presentations and informal discussions on a group
      email list by a European network of wildlife disease scientists from the European
      Wildlife Disease Association, or 6) identification as pathogens with changes in
      their epidemiology during 2010-16. The wildlife pathogens or diseases included in
      this review are: avian influenza virus, seal influenza virus, lagoviruses, rabies
      virus, bat lyssaviruses, filoviruses, canine distemper virus, morbilliviruses in
      aquatic mammals, bluetongue virus, West Nile virus, hantaviruses, Schmallenberg
      virus, Crimean-Congo hemorrhagic fever (CCHF) virus, African swine fever virus,
      amphibian ranavirus, hepatitis E virus, bovine tuberculosis ( Mycobacterium
      bovis), tularemia ( Francisella tularensis), brucellosis ( Brucella spp.),
      salmonellosis ( Salmonella spp.), Coxiella burnetii, chytridiomycosis,
      Echinococcus multilocularis, Leishmania infantum, and chronic wasting disease.
      Further work is needed to identify all of the key drivers of disease change and
      emergence, as they appear to be influencing the incidence and spread of these
      pathogens in Europe. We present a summary of these recent changes during 2010-16
      to discuss possible commonalities and drivers of disease change and to identify
      directions for future work on wildlife-related diseases in Europe. Many of the
      pathogens are entering Europe from other continents while others are expanding
      their ranges inside and beyond Europe. Surveillance for these wildlife-related
      diseases at a continental scale is therefore important for planet-wide
      assessment, awareness of, and preparedness for the risks they may pose to
      wildlife, domestic animal, and human health.

PMID- 30284965
TI  - "The Action Level"(r).

PMID- 30284964
TI  - Traditional herbalists' methods of treating mental disorders in Ghana.
AB  - The use of traditional medicine for the treatment of various disorders is not a
      new practice. Indeed, various categories of traditional healers form a large part
      of the healthcare workforce in many low- and middle-income countries, and given
      the paucity of mental health professionals in these countries, traditional and
      complementary medicine practitioners are utilised even more so for mental
      disorders. In Ghana, efforts have been made to formalise and standardise the work
      of traditional medicine practitioners. This goal is still mostly unmet, partly
      due to the lack of scientific knowledge of their beliefs, methods, and practices
      in mental healthcare. Very few studies have documented this knowledge. In this
      article, we report on some of the methods that are used by traditional Ghanaian
      herbalists in treating mental disorders. Eight herbalists working within the
      Greater Accra Region, who specialised in mental health, were interviewed through
      individual semi-structured interviews. Thematic analysis showed that traditional
      herbalists' work in treating mental disorders revolved around four key themes:
      the method of diagnosis; the treatment methods used; the mode of administering
      the treatment; and the purpose of the specific treatment. These themes are
      discussed with reference to their potential implications for patients' care and
      outcomes.

PMID- 30284966
TI  - Amnion-Based Scaffold with Enhanced Strength and Biocompatibility for In Vivo
      Vascular Repair.
AB  - Current vascular replacement grafts used in congenital heart defect corrective
      surgery have poor longevity and growth potential. Recipient patients often
      require multiple reoperations. Tissue engineering has the promise to produce a
      graft with the potential to grow, remodel, and repair. In this study, we aimed at
      developing an amnion-based scaffold suitable for cardiovascular tissue
      engineering applications and in vivo usage. The developed human amnion-based
      scaffold was made by an enzymatic decellularization process followed by freeze
      drying as a single or multilayered structure. These structures were compared to
      native amnion for seeded cell viability and biomechanical properties then tested
      for in vivo biocompatibility. Our results demonstrated that while native amnion
      tissue supported little cell growth, the decellularized-amnion allowed cell
      engraftment and survival. In addition, preservation of the scaffold by freeze
      drying as a single layer allowed cell engraftment and growth. Multilayering the
      freeze-dried amnion scaffolds resulted in a similar cell growth potential of the
      single layered construct but superior mechanical strength. The multilayered
      construct showed in vitro biocompatibility with endothelial cells, smooth muscle
      cells, cardiac myocytes, and thymus and cord blood-derived mesenchymal stem cells
      (MSCs). When implanted in a piglet model of left pulmonary artery grafting, the
      multilayered construct showed its in vivo suitability and biocompatibility for
      vascular repair as demonstrated by the development of newly formed endothelium in
      the intima, a smooth muscle cell-rich medial layer and an adventitia containing
      new vasa vasorum. In conclusion, our developed amnion-derived scaffold represents
      an off-the-shelf biocompatible structure that can be seeded with the patient's
      own MSCs to produce an autologous vascular graft.

PMID- 30284967
TI  - Animal models for stem cell-based pulp regeneration: Foundation for human
      clinical applications.
AB  - Rapid progress has been made in the last decade related to stem cell-mediated
      pulp-dentin regeneration, from characterization of dental pulp stem cells (DPSCs)
      to the first-ever reported clinical case in humans. However, many challenges
      still need to be addressed before such technology can become a common clinical
      practice; therefore, further rigorous research is needed. Animal study models are
      very important to test new ideas, concepts, and technologies. This review
      summarizes and discusses several key animal models that have been utilized to
      investigate pulp-dentin regeneration. From a tissue regeneration perspective, we
      categorize the animal model by the location where the regenerated pulp tissue is
      formed: ectopic, semi-orthotopic, and orthotopic. Several animal species are
      discussed, including mouse, ferret, dog, and mini-swine. Mouse is used for
      ectopic pulp-dentin regeneration in the dorsum subcutaneous space. A commonly
      tested approach is hydroxyapatite/tricalcium phosphate granules (HA-TCP) model
      used to observe ectopic pulp-dentin complex formation. The semi-orthotopic model
      includes tooth slices or fragments with which de novo pulp regeneration in a root
      canal space can be tested in the mouse subcutaneous space. For orthotopic pulp
      regeneration, the canine teeth of ferrets are large enough for such purposes. As
      non-primate large animal models, dog and mini-swine teeth have many aspects quite
      similar to those of humans, allowing researchers to perform experiments that
      mimic clinical conditions in humans. The protocols established and the data
      obtained from large animal studies may directly relate to and apply to future
      human studies. Complete orthotopic pulp regeneration has been demonstrated in
      dogs and mini-swine. The use of allogeneic and subpopulations of DPSCs for pulp
      regeneration, and testing of the periapical disease model and aging model have
      been performed in mini-swine or dogs. In sum, all these animal models will help
      to address challenges that still face pulp regeneration in humans. We need to
      thoroughly utilize these models to test new ideas, technologies, and strategies
      before reliable and predictable clinical protocols can be established for human
      clinical trials or treatment.

PMID- 30284968
TI  - Adjunctive colposcopy technologies for assessing suspected cervical
      abnormalities: systematic reviews and economic evaluation.
AB  - BACKGROUND: Dynamic Spectral Imaging System (DySIS)map (DySIS Medical Ltd,
      Edinburgh, UK) and ZedScan (Zilico Limited, Manchester, UK) can be used
      adjunctively with conventional colposcopy, which may improve the detection of
      cervical intraepithelial neoplasia (CIN) and cancer. OBJECTIVES: To
      systematically review the evidence on the diagnostic accuracy, clinical
      effectiveness and implementation of DySISmap and ZedScan as adjuncts to standard
      colposcopy, and to develop a cost-effectiveness model. METHODS: Four parallel
      systematic reviews were performed on diagnostic accuracy, clinical effectiveness
      issues, implementation and economic analyses. In January 2017 we searched
      databases (including MEDLINE and EMBASE) for studies in which DySISmap or ZedScan
      was used adjunctively with standard colposcopy to detect CIN or cancer in women
      referred to colposcopy. Risk of bias was assessed with the Quality Assessment of
      Diagnostic Accuracy Studies (QUADAS)-2 tool. Summary estimates of diagnostic
      accuracy were calculated using bivariate and other regression models when
      appropriate. Other outcomes were synthesised narratively. A patient-level state
      transition model was developed to evaluate the cost-effectiveness of DySISmap and
      ZedScan under either human papillomavirus (HPV) triage or the HPV primary
      screening algorithm. The model included two types of clinics ['see and treat' and
      'watchful waiting' (i.e. treat later after confirmatory biopsy)], as well as the
      reason for referral (low-grade or high-grade cytological smear). Sensitivity and
      scenario analyses were undertaken. RESULTS: Eleven studies were included in the
      diagnostic review (nine of DySISmap and two of ZedScan), three were included in
      the clinical effectiveness review (two of DySISmap and one of ZedScan) and five
      were included in the implementation review (four of DySISmap and one of ZedScan).
      Adjunctive DySISmap use was found to have a higher sensitivity for detecting CIN
      grade 2+ (CIN 2+) lesions [81.25%, 95% confidence interval (CI) 72.2% to 87.9%]
      than standard colposcopy alone (57.91%, 95% CI 47.2% to 67.9%), but with a lower
      specificity (70.40%, 95% CI 59.4% to 79.5%) than colposcopy (87.41%, 95% CI 81.7%
      to 91.5%). (Confidential information has been removed.) The base-case cost
      effectiveness results showed that adjunctive DySISmap routinely dominated
      standard colposcopy (it was less costly and more effective). The only exception
      was for high-grade referrals in a watchful-waiting clinic setting. The
      incremental cost-effectiveness ratio for ZedScan varied between L272 and L4922
      per quality-adjusted life-year. ZedScan also dominated colposcopy alone for high
      grade referrals in see-and-treat clinics. These findings appeared to be robust to
      a wide range of sensitivity and scenario analyses. LIMITATIONS: All but one study
      was rated as being at a high risk of bias. There was no evidence directly
      comparing ZedScan with standard colposcopy. No studies directly compared DySIS
      and ZedScan. CONCLUSIONS: The use of adjunctive DySIS increases the sensitivity
      for detecting CIN 2+, so it increases the number of high-grade CIN cases that are
      detected. However, it also reduces specificity, so that more women with no or low
      grade CIN will be incorrectly judged as possibly having high-grade CIN. The
      evidence for ZedScan was limited, but it appears to increase sensitivity and
      decrease specificity compared with colposcopy alone. The cost-effectiveness of
      both adjunctive technologies compared with standard colposcopy, under both the
      HPV triage and primary screening algorithms, appears to be favourable when
      compared with the conventional thresholds used to determine value in the NHS.
      FUTURE WORK: More diagnostic accuracy studies of ZedScan are needed, as are
      studies assessing the diagnostic accuracy for women referred to colposcopy as
      part of the HPV primary screening programme. STUDY REGISTRATION: This study is
      registered as PROSPERO CRD42017054515. FUNDING: The National Institute for Health
      Research Health Technology Assessment programme.

PMID- 30284970
TI  - Structural properties of silicon-germanium and germanium-silicon core-shell
      nanowires.
AB  - Core-shell nanowires made of Si and Ge can be grown experimentally with excellent
      control for different sizes of both core and shell. We have studied the
      structural properties of Si/Ge and Ge/Si core-shell nanowires aligned along the
      [Formula: see text] direction, with diameters up to 10.2 nm and varying core to
      shell ratios, using linear scaling density functional theory. We show that
      Vegard's law, which is often used to predict the axial lattice constant, can lead
      to an error of up to 1%, underlining the need for a detailed ab initio atomistic
      treatment of the nanowire structure. We analyse the character of the intrinsic
      strain distribution and show that, regardless of the composition or bond
      direction, the Si core or shell always expands. In contrast, the strain patterns
      in the Ge shell or core are highly sensitive to the location, composition and
      bond direction. The highest strains are found at heterojunction interfaces and
      the surfaces of the nanowires. This detailed understanding of the atomistic
      structure and strain paves the way for studies of the electronic properties of
      core-shell nanowires and investigations of doping and structure defects.

PMID- 30284971
TI  - Role of weak C-H...O and strong N-H...O intermolecular interactions on the high
      symmetry molecular packing of trans-cyclohexane-1,4-dicarboxamide.
AB  - An unpredicted fourfold screw N-H...O hydrogen bond C(4) motif in a primary
      dicarboxamide (trans-cyclohexane-1,4-dicarboxamide, C8H14N2O2) was investigated
      by single-crystal X-ray diffraction and IR and Raman spectroscopies. Electron
      density topology and intermolecular energy analyses determined from ab initio
      calculations were employed to examine the influence of weak C-H...O hydrogen-bond
      interactions on the peculiar arrangement of molecules in the tetragonal P43212
      space group. In addition, the way in which the co-operative effects of those weak
      bonds might modify their relative influence on molecular packing was estimated
      from cluster calculations. Based on the results, a structural model is proposed
      which helps to rationalize the unusual fourfold screw molecular arrangement.

PMID- 30284969
TI  - Cellular localization of the cell cycle inhibitor Cdkn1c controls growth arrest
      of adult skeletal muscle stem cells.
AB  - Adult skeletal muscle maintenance and regeneration depend on efficient muscle
      stem cell (MuSC) functions. The mechanisms coordinating cell cycle with
      activation, renewal, and differentiation of MuSCs remain poorly understood. Here,
      we investigated how adult MuSCs are regulated by CDKN1c (p57kip2), a cyclin
      dependent kinase inhibitor, using mouse molecular genetics. In the absence of
      CDKN1c, skeletal muscle repair is severely impaired after injury. We show that
      CDKN1c is not expressed in quiescent MuSCs, while being induced in activated and
      proliferating myoblasts and maintained in differentiating myogenic cells. In
      agreement, isolated Cdkn1c-deficient primary myoblasts display differentiation
      defects and increased proliferation. We further show that the subcellular
      localization of CDKN1c is dynamic; while CDKN1c is initially localized to the
      cytoplasm of activated/proliferating myoblasts, progressive nuclear translocation
      leads to growth arrest during differentiation. We propose that CDKN1c activity is
      restricted to differentiating myoblasts by regulated cyto-nuclear relocalization,
      coordinating the balance between proliferation and growth arrest.

PMID- 30284972
TI  - Crystal structure of the thortveitite-related M phase, (MnxZn1-x)2V2O7 (0.75 < x
      < 0.913): a combined synchrotron powder and single-crystal X-ray study.
AB  - The determination of the crystal structure of the M phase, (MnxZn1-x)2V2O7 (0.75
      < x < 0.913), in the pseudobinary Mn2V2O7-Zn2V2O7 system for x ? 0.8 shows that
      the previously published triclinic unit-cell parameters for this thortveitite
      related phase do not describe a true lattice for this phase. Instead, single
      crystal X-ray data and Rietveld refinement of synchrotron X-ray powder data show
      that the M phase has a different triclinic structure in the space group P-1 with
      Z = 2. As prior work has suggested, the crystal structure can be described as a
      distorted version of the thortveitite crystal structure of beta-Mn2V2O7. A
      twofold superstructure in diffraction patterns of crystals of the M phase used
      for single-crystal X-ray diffraction work arises from twinning by reticular
      pseudomerohedry. This superstructure can be described as a commensurate
      modulation of a pseudo-monoclinic basis structure closely related to the crystal
      structure of beta-Mn2V2O7. In comparison with the distortions introduced when
      beta-Mn2V2O7 transforms at low temperature to alpha-Mn2V2O7, the distortions
      which give rise to the M phase from the beta-Mn2V2O7 prototype are noticeably
      less pronounced.

PMID- 30284973
TI  - The new heteropolyoxometalate compound (C6H8N)5[HAs2Mo6O26(H2O)].3H2O: crystal
      structure and Hirshfeld surface analysis.
AB  - A detailed description of the crystal structure and a Hirshfeld surface analysis
      of the new heteropolyoxometalate compound (C6H8N)5[HAs2Mo6O26(H2O)].3H2O are
      reported. The title compound was synthesized using solution methods and its
      structure was characterized by single-crystal X-ray diffraction. The investigated
      compound contains a new [HAs2Mo6O26(H2O)]5- polyanion and crystallizes in the
      monoclinic space group P21/c. The crystallographic analysis provided an
      understanding of the architecture and structural features of the complex crystal
      lattice and the Hirshfeld surface analysis shed more light on the intermolecular
      interactions occurring in the crystal.

PMID- 30284974
TI  - Eight Schiff bases derived from various salicylaldehydes: phenol-imine and keto
      amine forms, conformational disorder, and supramolecular assembly in one and two
      dimensions.
AB  - Structures are reported for eight Schiff bases derived from various
      salicylaldehydes: five are newly synthesized and re-investigations are reported
      for three previously reported structures, leading, in each case, to some revision
      of previous conclusions. In (E)-N-(3,4-dimethylisoxazol-5-yl)-4-[(2
      hydroxybenzylidene)amino]benzenesulfonamide, C18H17N3O4S, (I), and (E)-4-[(5
      bromo-2-hydroxy-3-methoxybenzylidene)amino]-N-(3,4-dimethylisoxazol-5
      yl)benzenesulfonamide. C19H18BrN3O5S, (II), the isoxazole rings adopt different
      orientations relative to the rest of the molecules, despite the additional
      substituents in (II) being in the aryl ring remote from the isoxazole unit. The
      molecules of both (E)-4-bromo-2-[(2-hydroxyphenylimino)methyl]-6-methoxyphenol,
      C14H12BrNO3, (III), and (E)-4-bromo-2-methoxy-6-[(2
      methoxyphenylimino)methyl]phenol, C15H14BrNO3, (IV), are both effectively planar;
      while (III) adopts the phenol-imine constitution, (IV) adopts the keto-amine
      constitution. (E)-2-Methoxy-6-[(2-methoxyphenylimino)methyl]phenol, C15H15NO3,
      (V), which was determined previously using powder X-ray data assuming the phenol
      imine constitution, has now been refined from single-crystal X-ray data,
      confirming the phenol-imine constitution. In (E)-3-benzoyl-2-[(5-fluoro-2
      hydroxybenzylidene)amino]-4,5,6,7-tetrahydrobenzo[b]thiophene, C22H18FNO2S, (VI),
      the fused carbocyclic ring exhibits conformational disorder; both disorder
      components, having populations of 0.705 (4) and 0.295 (4), adopt half-chair
      conformations. The isostructural (E)-3-benzoyl-2-[(2-hydroxybenzylidene)amino)]
      4,5,6,7-tetrahydrobenzo[b]thiophene, C22H19NO2S, (VII), which was originally
      reported as having a fully ordered structure [Kaur et al. (2014). Acta Cryst.
      E70, o476-o477], has been rerefined using the original data set and found to
      exhibit the same type of disorder as found in (VI), with disordered populations
      having occupancies of 0.851 (3) and 0.149 (3). The triclinic polymorph of (E)-[(2
      hydroxyphenylimino)methyl]phenol, C13H11NO2, (VIII), which crystallizes with Z' =
      2 in the space group P-1, has been described variously as occurring as the keto
      amine tautomer [Maciejewska et al. (1999). J. Phys. Org. Chem. 12, 875-880] and
      as the phenol-imine tautomer [Tunc et al. (2009). J. Chem. Crystallogr. 39, 672
      676]. Rerefinement of this structure using one of the original data sets shows
      that both of the independent molecules exist in the keto-amine form. In the
      structures of compounds (I), (VI), (VII) and (VIII), hydrogen bonds generate
      simple chains, while a chain of rings is formed in (V). Sheets are formed by
      hydrogen bonds in both (II) and (III), while in (IV), the sheet structure is
      built from aromatic pi-pi stacking interactions.

PMID- 30284975
TI  - Different coordination modes of trans-2-{[(2-methoxyphenyl)imino]methyl}phenoxide
      in rare-earth complexes: influence of the metal cation radius and the number of
      ligands on steric congestion and ligand coordination modes.
AB  - A simple and effective synthetic route to homo- and heteroleptic rare-earth (Ln =
      Y, La and Nd) complexes with a tridentate Schiff base anion has been demonstrated
      using exchange reactions of rare-earth chlorides with in-situ-generated sodium
      (E)-2-{[(2-methoxyphenyl)imino]methyl}phenoxide in different molar ratios in
      absolute methanol. Five crystal structures have been determined and studied,
      namely tris(2-{[(2-methoxyphenyl)imino]methyl}phenolato-kappa3O1,N,O2)lanthanum,
      [La(C14H12NO2)3], (1), tris(2-{[(2-methoxyphenyl)imino]methyl}phenolato
      kappa3O1,N,O2)neodymium tetrahydrofuran disolvate, [La(C14H12NO2)3].2C4H8O,
      (2).2THF, tris(2-{[(2-methoxyphenyl)imino]methyl}phenolato)
      kappa3O1,N,O2;kappa3O1,N,O2;kappa2N,O1-yttrium, [Y(C14H12NO2)3], (3), dichlorido
      1kappaCl,2kappaCl-MU-methanolato-1:2kappa2O:O-methanol-2kappaO-(MU-2-{[(2
      methoxyphenyl)imino]methyl}phenolato-1kappa3O1,N,O2:2kappaO1)bis(2-{[(2
      methoxyphenyl)imino]methyl}phenolato)-1kappa3O1,N,O2;2kappa3O1,N,O2-diyttrium
      tetrahydrofuran-methanol (1/1/1), [Y2(C14H12NO2)3(CH3O)Cl2(CH4O)].CH4O.C4H8O,
      (4).MeOH.THF, and bis(MU-2-{[(2-methoxyphenyl)imino]methyl}phenolato
      1kappa3O1,N,O2:2kappaO1)bis(2-{[(2-methoxyphenyl)imino]methyl}phenolato
      2kappa3O1,N,O2)sodiumyttrium chloroform disolvate, [NaY(C14H12NO2)4].2CHCl3,
      (5).2CHCl3. Structural peculiarities of homoleptic tris(iminophenoxide)s (1)-(3),
      binuclear tris(iminophenoxide) (4) and homoleptic ate tetrakis(iminophenoxide)
      (5) are discussed. The nonflat Schiff base ligand displays MU2
      kappa3O1,N,O2:kappaO1 bridging, and kappa3O1,N,O2 and kappa2N,O1 terminal
      coordination modes, depending on steric congestion, which in turn depends on the
      ionic radii of the rare-earth metals and the number of coordinated ligands. It
      has been demonstrated that interligand dihedral angles of the phenoxide ligand
      are convenient for comparing steric hindrance in complexes. (4).MeOH has a flat
      Y2O2 rhomboid core and exhibits both inter- and intramolecular MeO-H...Cl
      hydrogen bonding. Catalytic systems based on complexes (1)-(3) and (5) have
      demonstrated medium catalytic performance in acrylonitrile polymerization,
      providing polyacrylonitrile samples with narrow polydispersity.

PMID- 30284976
TI  - Synthesis of ReI tricarbonyl complexes with various sulfur- and oxygen-donating
      ligands: crystal structures of two ReI dinuclear structures bridged by S atoms.
AB  - The synthesis and characterization of two dinuclear complexes, namely fac
      hexacarbonyl-1kappa3C,2kappa3C-(pyridine-1kappaN)[MU-2,2'
      sulfanediyldi(ethanethiolato)-1kappa2S1,S3:2kappa3S1,S2,S3]dirhenium(I),
      [Re2(C4H8S3)(C5H5N)(CO)6], (1), and tetraethylammonium fac-tris(MU-2
      methoxybenzenethiolato-kappa2S:S)bis[tricarbonylrhenium(I)],
      (C8H20N)[Re2(C7H7OS)3(CO)6], (2), together with two mononuclear complexes, namely
      (2,2'-bithiophene-5-carboxylic acid-kappa2S,S')bromidotricarbonylrhenium(I), (3),
      and bromidotricarbonyl(methyl benzo[b]thiophene-2-carboxylate
      kappa2O,S)rhenium(I), (4), are reported. Crystals of (1) and (2) were
      characterized by X-ray diffraction. The crystal structure of (1) revealed two Re
      S-Re bridges. The thioether S atom only bonds to one of the ReI metal centres,
      while the geometry of the second ReI metal centre is completed by a pyridine
      ligand. The structure of (2) is characterized by three S-atom bridges and an
      Re...Re nonbonding distance of 3.4879 (5) A, which is shorter than the distance
      found for (1) [3.7996 (6)/3.7963 (6) A], but still clearly a nonbonding distance.
      Complex (1) is stabilized by six intermolecular hydrogen-bond interactions and an
      O...O interaction, while (2) is stabilized by two intermolecular hydrogen-bond
      interactions and two O...pi interactions.

PMID- 30284977
TI  - A new two-dimensional CoII coordination polymer based on bis[4-(2-methyl-1H
      imidazol-1-yl)phenyl] ether and biphenyl-4,4'-diyldicarboxylic acid: synthesis,
      crystal structure and photocatalytic degradation activity.
AB  - A novel two-dimensional CoII coordination framework, namely poly[(MU2-biphenyl
      4,4'-diyldicarboxylato-kappa2O4:O4'){MU2-bis[4-(2-methyl-1H-imidazol-1-yl)phenyl]
      ether-kappa2N3:N3'}cobalt(II)], [Co(C14H8O4)(C20H18N4O)]n, has been prepared and
      characterized by IR, elemental analysis, thermal analysis and single-crystal X
      ray diffraction. The crystal structure reveals that the compound has an achiral
      two-dimensional layered structure based on opposite-handed helical chains. In
      addition, it exhibits significant photocatalytic degradation activity for the
      degradation of methylene blue.

PMID- 30284978
TI  - A new one-dimensional CdII coordination polymer incorporating 2,2'-(1,2
      phenylene)bis(1H-imidazole-4,5-dicarboxylate).
AB  - Imidazole-4,5-dicarboxylic acid (H3IDC) and its derivatives are widely used in
      the preparation of new coordination polymers owing to their versatile bridging
      coordination modes and potential hydrogen-bonding donors and acceptors. A new one
      dimensional coordination polymer, namely catena-poly[[diaquacadmium(II)]-MU3-2,2'
      (1,2-phenylene)bis(1H-imidazole-4,5-dicarboxylato)], [Cd(C16H6N4O8)0.5(H2O)2]n or
      [Cd(H2Phbidc)1/2(H2O)2]n, has been synthesized by the reaction of Cd(OAc)2.2H2O
      (OAc is acetate) with 2,2'-(1,2-phenylene)bis(1H-imidazole-4,5-dicarboxylic acid)
      (H6Phbidc) under solvothermal conditions. In the polymer, one type of Cd ion
      (Cd1) is six-coordinated by two N atoms and two O atoms from one H2Phbidc4-
      ligand and by two O atoms from two water molecules, forming a significantly
      distorted octahedral CdN2O4 coordination geometry. In contrast, the other type of
      Cd ion (Cd2) is six-coordinated by two N atoms and two O atoms from two symmetry
      related H2Phbidc4- ligands and by two O atoms from two symmetry-related water
      molecules, leading to a more regular octahedral coordination geometry. The Cd1
      and Cd2 ions are linked by H2Phbidc4- ligands into a one-dimensional chain which
      runs parallel to the b axis. In the crystal, the one-dimensional chains are
      connected through hydrogen bonds, generating a two-dimensional layered structure
      parallel to the ab plane. Adjacent layers are further linked by hydrogen bonds,
      forming a three-dimensional structure in the solid state.

PMID- 30284979
TI  - A new ZnII coordination polymer based on 4-(pyridin-4-yl)benzoic and formic
      acids: in-situ synthesis, crystal structure and luminescence properties.
AB  - The title compound, poly[(MU2-formato-kappa3O,O':O)[MU2-4-(pyridin-4-yl)benzoato
      kappa3N:O,O']zinc(II)], [Zn(C12H8NO2)(HCOO)]n, has been synthesized in situ and
      characterized by thermogravimetric analysis (TGA) and single-crystal and powder X
      ray diffraction analyses. The polymer contains two independent structural units
      in the asymmetric unit. These are constructed from Zn2+ ions, 4-(pyridin-4
      yl)benzoate (4-pbc) bridges and in-situ-generated formate ligands, forming two
      similar two-dimensional (2D) layer structures. These similar 2D layers are
      arranged alternately and are linked with each other by dense C-H...O hydrogen
      bonds to generate a three-dimensional (3D) supramolecular framework. The crystal
      is pseudomerohedrally twinned about [201]. Compared with free 4-Hpbc, the polymer
      exhibits a red shift and significantly enhanced solid-state luminescence
      properties.

PMID- 30284980
TI  - Synthesis, crystal structure and cytotoxic activity of novel 5-methyl-4
      thiopyrimidine derivatives.
AB  - This article presents the synthesis of three new 4-thiopyrimidine derivatives
      obtained from ethyl 4-methyl-2-phenyl-6-sulfanylpyrimidine-5-carboxylate as the
      starting material, namely, ethyl 4-[(4-chlorobenzyl)sulfanyl]-6-methyl-2
      phenylpyrimidine-5-carboxylate, C21H19ClN2O2S, (2), {4-[(4-chlorobenzyl)sulfanyl]
      6-methyl-2-phenylpyrimidin-5-yl}methanol, C19H17ClN2OS, (3), and 4-[(4
      chlorobenzyl)sulfanyl]-5,6-dimethyl-2-phenylpyrimidine, C19H17ClN2S, (4), which
      vary in the substituent at the 5-position of the pyrimidine ring. The compounds
      were characterized by 1H NMR, 13C NMR, IR and mass spectroscopies, and also
      elemental analysis. The molecular structures were further studied by single
      crystal X-ray diffraction. Compound (2) crystallizes in the space group P-1 with
      one molecule in the asymmetric unit, whereas compounds (3) and (4) crystallize in
      the space group P21/c with two and one molecule, respectively, in their
      asymmetric units. The conformation of each molecule is best defined by the
      dihedral angles formed between the pyrimidine ring and the planes of the two aryl
      substituents attached at the 2- and 4-positions. The only structural difference
      between the three compounds is the substituent at the 5-position of the
      pyrimidine ring, but they present significantly different features in the
      hydrogen-bond interactions. Compound (2) displays a one-dimensional chain formed
      by hydrogen bonds and the chains are further extended into a two-dimensional
      network. Molecules of (3) and (4) generate one-dimensional chains formed through
      intermolecular interactions. The study examines the cytotoxicity of compounds (3)
      and (4) against Human umbilical vein endothelial cells (HUVEC) and HeLa, K562 and
      CFPAC cancer cell lines. The presence of the hydroxymethyl and methyl groups in
      (3) and (4), respectively, offers an interesting new insight into the structures
      and behaviour of these derivatives. Compound (4) was found to be nontoxic against
      CFPAC and HUVEC; however, it shows weak activity against the HeLa and K563 cell
      lines. The presence of a hydroxy group in (3) significantly increases its
      cytotoxicity towards both, i.e. the cancer (HeLa, K562 and CFPAC) and normal
      (HUVEC) cell lines.

PMID- 30284981
TI  - Syntheses, crystal structures and optical properties of two one-dimensional
      germanophosphates: HRb3Ge2(HPO4)6 and CsGe(HPO4)2(OH).
AB  - Germanophosphates, as a young class of metal phosphates, have been less reported
      but might possess more diverse structural types and potential applications. Here,
      two one-dimensional (1D) alkali-metal germanophosphates (GePOs), namely, hydrogen
      hexakis(MU-hydrogen phosphato)digermaniumtrirubidium, HRb3Ge2(HPO4)6 (1), and
      caesium bis(MU-hydrogen phosphato)(MU-hydroxido)germanium, CsGe(HPO4)2(OH) (2),
      have been prepared by the solvothermal method. Compound 1 shows 1D
      [Ge(HPO4)6]infinity chains along the c axis formed by GeO6 octahedra and PO4
      tetrahedra, with Rb+ cations dissociated between the chains. Compound 2 also
      exhibits 1D [Ge(HPO4)4(OH)2]infinity chains constructed from adjacent
      Ge(HPO4)4(OH)2 octahedra, with Cs+ cations dissociated between the chains. XRD,
      TGA, IR and UV-Vis-NIR absorption spectra are presented and discussed for both
      compounds.

PMID- 30284982
TI  - Crystal structure and sequential dehydration transitions of disodium guanosine 5'
      monophosphate tetrahydrate.
AB  - Disodium guanosine 5'-monophosphate was reported previously to crystallize as
      both the tetrahydrate and the heptahydrate. We herein report a determination of
      the molecular and crystal structures of the title tetrahydrated salt,
      2Na+.C10H12N5O8P2-.4H2O. It was found that the structure differs markedly from
      that of the heptahydrate, but greatly resembles that of disodium deoxyguanosine
      5'-monophosphate tetrahydrate. The C2'-O2'H moiety of ribose is surrounded by
      hydrophilic moieties and is disordered over two sites. The sugar puckering mode
      is O4'-endo-C1'-exo at both sites and the conformation around the C4'-C5' bond is
      gauche-trans. Powder X-ray diffraction and thermal analyses revealed that the
      temperature-controlled transition from the tetrahydrate to the anhydride
      proceeded through three intermediate phases between 40 and 60  degrees C at 0%
      relative humidity. Large induction periods were observed.

PMID- 30284983
TI  - Dilithium (citrate) crystals and their relatives.
AB  - New compounds of the type LiMHC6H5O7 (M = Li, Na, K, Rb) have been prepared from
      the metal carbonates and citric acid in solution. The crystal structures have
      been solved and refined using laboratory powder X-ray diffraction data, and
      optimized using density functional techniques. The compounds crystallize in the
      triclinic space group P-1 and are nearly isostructural. The structures are
      lamellar, with the layers in the ab plane. The boundaries of the layers consist
      of hydrophobic methylene groups and very strong intermolecular O-H...O hydrogen
      bonds. The O...O distances range from 2.666 A for M = Li to 2.465 A for M = Rb.
      The Li-O bonds exhibit significant covalent character, while the heavier M-O
      bonds are ionic. The Li atoms are four-, five-, or six-coordinate, while the
      coordination numbers of the larger cations are higher, i.e. eight for Na and nine
      for K and Rb. The citrate anion occurs in the trans,trans conformation, one of
      the two low-energy conformations of an isolated citrate anion. The crystal
      structure of LiRbHC6H5O7.H2O was also solved and refined. It consists of the same
      layers as in the anhydrous M = Rb compound, with interlayer water molecules and a
      different hydrogen-bonding pattern.

PMID- 30284985
TI  - Notch signaling suppresses glucose metabolism in mesenchymal progenitors to
      restrict osteoblast differentiation.
AB  - Notch signaling critically controls cell fate decisions in mammals, both during
      embryogenesis and in adults. In the skeleton, Notch suppresses osteoblast
      differentiation and sustains bone marrow mesenchymal progenitors during postnatal
      life. Stabilizing mutations of Notch2 cause Hajdu-Cheney syndrome, which is
      characterized by early-onset osteoporosis in humans, but the mechanism whereby
      Notch inhibits bone accretion is not fully understood. Here, we report that
      activation of Notch signaling by either Jagged1 or the Notch2 intracellular
      domain suppresses glucose metabolism and osteoblast differentiation in primary
      cultures of bone marrow mesenchymal progenitors. Importantly, deletion of Notch2
      in the limb mesenchyme increases both glycolysis and bone formation in the long
      bones of postnatal mice, whereas pharmacological reduction of glycolysis
      abrogates excessive bone formation. Mechanistically, Notch reduces the expression
      of glycolytic and mitochondrial complex I genes, resulting in a decrease in
      mitochondrial respiration, superoxide production, and AMPK activity. Forced
      activation of AMPK restores glycolysis in the face of Notch signaling. Thus,
      suppression of glucose metabolism contributes to the mechanism, whereby Notch
      restricts osteoblastogenesis from bone marrow mesenchymal progenitors.

PMID- 30284984
TI  - Synthesis, crystal structures and anti-inflammatory activity of four 3,5
      bis(arylidene)-N-benzenesulfonyl-4-piperidone derivatives.
AB  - 3,5-Bis(arylidene)-4-piperidone (BAP) derivatives display good antitumour and
      anti-inflammatory activities because of their double alpha,beta-unsaturated
      ketone structural characteristics. If N-benzenesulfonyl substituents are
      introduced into BAPs, the configuration of the BAPs would change significantly
      and their anti-inflammatory activities should improve. Four N-benzenesulfonyl
      BAPs, namely (3E,5E)-1-(4-methylbenzenesulfonyl)-3,5-bis[4
      (trifluoromethyl)benzylidene]piperidin-4-one dichloromethane monosolvate,
      C28H21F6NO3S.CH2Cl2, (4), (3E,5E)-1-(4-fluorobenzenesulfonyl)-3,5-bis[4
      (trifluoromethyl)benzylidene]piperidin-4-one, C27H18F7NO3S, (5), (3E,5E)-1-(4
      nitrobenzenesulfonyl)-3,5-bis[4-(trifluoromethyl)benzylidene]piperidin-4-one,
      C27H18F6N2O5S, (6), and (3E,5E)-1-(4-cyanobenzenesulfonyl)-3,5-bis[4
      (trifluoromethyl)benzylidene]piperidin-4-one dichloromethane monosolvate,
      C28H18F6N2O3S.CH2Cl2, (7), were prepared by Claisen-Schmidt condensation and N
      sulfonylation. They were characterized by NMR, FT-IR and HRMS (high resolution
      mass spectrometry). Single-crystal structure analysis reveals that the two 4
      (trifluoromethyl)phenyl rings on both sides of the piperidone ring in (4)-(7)
      adopt an E stereochemistry of the olefinic double bonds. Molecules of both (4)
      and (6) are connected by hydrogen bonds into one-dimensional chains. In (5) and
      (7), pairs of adjacent molecules embrace through intermolecular hydrogen bonds to
      form a bimolecular combination, which are further extended into a two-dimensional
      sheet. The anti-inflammatory activity data reveal that (4)-(7) significantly
      inhibit LPS-induced interleukin (IL-6) and tumour necrosis factor (TNF-alpha)
      secretion. Most importantly, (6) and (7), with strong electron-withdrawing
      substituents, display more potential inhibitory effects than (4) and (5).

PMID- 30284986
TI  - Patterns and sociodemographic characteristics of substance abuse in Al Qassim,
      Saudi Arabia: a retrospective study at a psychiatric rehabilitation center.
AB  - BACKGROUND: The problem of substance abuse is one of the top 20 risk factors for
      poor health worldwide. Though widely prevalent in the Middle East, there are few
      studies in Saudi Arabia. OBJECTIVE: Record the pattern of substances abuse and
      the sociodemographic characteristics of abusers attending the local
      rehabilitation center. DESIGN: Descriptive, retrospective medical record review.
      SETTING: Patients admitted to psychiatric rehabilitation center. METHODS: The
      sample included all patients admitted to a rehabilitation center during the
      period of January 2016-December 2016. Data was collected retrospectively from
      patient records. MAIN OUTCOME MEASURES: Descriptive epidemiological data and
      statistical comparisons. SAMPLE SIZE: 612 patients. RESULTS: The majority of
      patients (73%) were 21-40 years of age. Polysubstance abuse (60%) and amphetamine
      (24%) abuse were most predominant in the 20-40 year olds (45%) and high school
      dropouts (41%). The average number of drugs being used by polysubstance abusers
      was 2.5 (and the maximum was 6). There was no relationship of family history of
      drug abuse and mental illness. CONCLUSION: There was an increased use of
      polysubstances and amphetamine with a decreased abuse of prescription drugs when
      compared to previous studies reported in Saudi Arabia. There was a decreasing
      prevalence for heroin and alcohol. Substance abusers have certain
      epidemiological, social and drug patterns and we recommend that authorities and
      planners integrate their efforts to look for the reasons for substance abuse.
      LIMITATIONS: Females not included and prevalence of tobacco smoking not studied.
      CONFLICT OF INTEREST: None.

PMID- 30284987
TI  - Expression of androgen receptor in invasive ductal breast carcinomas: a
      clinicopathological study from Jordan.
AB  - BACKGROUND: The clinical relevance of androgen receptors (ARs) expressed in
      breast cancer cells and the suggested prognostic impact has been an area of
      active research. The prevalence rate of AR expression in breast cancer has never
      been reported among Jordanian patients. OBJECTIVE: Determine the expression rate
      of ARs among invasive ductal breast cancer cases of different stages and
      molecular subtypes. Also, analyze the relationship between AR expression and
      clinicopathologic and immunohistochemical criteria, and assess the impact of AR
      expression on survival. DESIGN: Retrospective medical record review. SETTING:
      Tertiary care hospital in Amman, Jordan. PATIENTS AND METHODS: Our study
      comprised only of cases of invasive ductal breast carcinoma of no special type
      among females from records during a 10-year period between 2006 and 2015.
      Immunohistochemical staining was considered positive if more than 10% of tumor
      nuclei showed positive staining. MAIN OUTCOME MEASURES: The expression rate of
      ARs and the association of the expression rate with the clinicopathologic
      features of invasive breast cancer. SAMPLE SIZE: 293. RESULTS:
      Immunohistochemical staining for AR revealed positive stain.ing in 180 (61.4%)
      cases, including approximately 50% of triple-negative breast cancer cases. AR
      positivity correlated with estrogen receptor (ER) status (P=.007) and smaller T
      size (P=.014). However, no significant association was found with any of the
      other variables. AR expression was positively associated with overall survival
      (P=.022) in general and in ER-positive cases (P=.012). However, in the
      multivariate Cox regression model, AR was not independently associated with
      survival. CONCLUSIONS: These results were consistent with international reports
      showing a significant relationship of AR expression with ER status. In addition,
      AR expression was significantly associated with smaller tumor size. Although AR
      status was not independently associated with survival, our data suggest AR is a
      good prognostic factor. LIMITATIONS: Some clinical data were missing. CONFLICT OF
      INTEREST: None.

PMID- 30284988
TI  - An 18-year study of thyroid carcinoma in the western region of Saudi Arabia: a
      retrospective single-center study in a community hospital.
AB  - BACKGROUND: Thyroid carcinoma (TC) is the ninth most common site of all cancers
      in women in the world and the second most common malignancy in Saudi Arabia. This
      reports updates data on the epidemiology of the disease in Saudi Arabia.
      OBJECTIVE: Describe and interpret changes in the frequency of TC to compare with
      other populations and determine proportions of certain histological types of TC.
      DESIGN: Medical record review. SETTING: Military hospital in Jeddah, Saudi
      Arabia. PATIENTS AND METHODS: We reviewed the pathological and clinical records
      from January 2000 to December 2017 of patients with TC. MAIN OUTCOME MEASURES:
      Frequency and types of TC. SAMPLE SIZE: 347 patients. RESULTS: Over the 18-year
      period, out of 456 patients with TC, 347 patients had sufficiently complete
      records: 275 (79.3%) were female and 72 (20.7%) were male for a female to male
      ratio of 3.8:1. The mean (SD) age at surgery of all patients was 45.2 (16.0)
      years. There were 287 (82.7%) cases of papillary TC. The next common malignancy
      was follicular TC with 32 (9.2%) cases followed by Hurthle cell cancer with 11
      (3.2%) cases. Lymphoma was found in only 7 (2%) cases. All TC types occurred at a
      younger age in females than males except for lymphoma. All TC types occurred with
      the greatest frequency in the fourth and fifth decades. There was a 2.3-fold
      increase in the number of TCs from 8 (2.3%) in 2000 to 26 (7.5%) in 2017. The
      rate per 100000 residents of Jeddah increased for the period from 2000 to 2002
      from 1.6 to 3.4 for 2015-2017. Papillary TC cases in females accounted for most
      of the increase. CONCLUSION: Our findings are consistent with similar studies
      worldwide. Etiological factors promoting the rise in TC must be investigated and
      may provide insight in developing suitable management strategies for the Saudi
      population. LIMITATION: Small sample size and retrospective over a long period.
      CONFLICT OF INTEREST: None.

PMID- 30284989
TI  - Outcomes and hospital admission patterns in patients with diabetes during Ramadan
      versus a non-fasting period.
AB  - BACKGROUND: Fasting during Ramadan is a challenge for Muslim patients with
      diabetes and for their healthcare providers. However, data on the effects of
      Ramadan fasting on hospital admissions and outcomes in patients with diabetes are
      scarce. OBJECTIVES: Evaluate the characteristics of patients with diabetes
      admitted during the fasting month of Ramadan compared with the non-fasting month
      of Dhu al-Qidah. DESIGN: A retrospective cohort study medical record review.
      SETTING: A university teaching hospital. PATIENTS AND METHODS: We reviewed the
      records of all patients with diabetes admitted to the medical department at
      Benghazi Medical Center, including medical ward, intensive care unit and coronary
      care unit, during the months of Ramadan and Dhu al-Qidah, 2016. We compared
      differences in reasons for admission, length of stay and in-hospital mortality
      between patients admitted during Ramadan and Dhu al-Qidah and between patients
      who were fasting at time of admission during Ramadan and those who were not. MAIN
      OUTCOME MEASURES: Main reason for admission, length of stay and in-hospital
      mortality rate. SAMPLE SIZE: 402 patients with diabetes. RESULTS: During Ramadan,
      186 patients were admitted compared with 216 during Dhul al-Qidah. There was no
      statistically significant difference in reasons for admission, length of hospital
      stay, or in-hospital mortality (borderline for mortality, P=.078), between
      patients with diabetes admitted during Ramadan and Dhu al-Qidah. Of those
      admitted in Ramadan, 59.1% were fasting on admission. Fasting patients admitted
      during Ramadan had a significantly higher proportion of the diseases of the
      circulatory system when compared with non-fasting patients (39.4% vs. 23.6%,
      P=.028) while in-hospital mortality was higher in non-fasting patients (29.2% vs.
      8.7%, P less than .001). There was no significant difference in length of stay
      between fasting and non-fasting patients. CONCLUSIONS: The frequency of
      admissions for most medical con.ditions were not changed during Ramadan but the
      frequency of acute coronary syndrome was higher in those who were fasting on
      admission. Patients with diabetes who were not fasting on admission had more high
      risk features that prevented them from fasting and therefore are at increased
      risk of in-hospital mortality. LIMITATIONS: Single center and retrospective.
      CONFLICT OF INTEREST: None.

PMID- 30284990
TI  - Implementation of total laboratory automation at a tertiary care hospital in
      Saudi Arabia: effect on turnaround time and cost efficiency.
AB  - BACKGROUND: Total laboratory automation (TLA) is a relatively new way of
      improving the management of high volume clinical laboratories. TLA may reduce
      staff, reduce operating costs, decrease testing time and provide enhanced process
      control. OBJECTIVES: Establish a cost efficient TLA that is less labor intensive,
      improves productivity and reduces turnaround time (TAT). DESIGN: Implementation
      of TLA for random glucose and troponin-T as sentinel tests to compare change in
      TAT. SETTING: Tertiary hospital with high volume of laboratory tests. METHODS:
      Routine patient samples for random glucose and troponin-T were used to capture
      TAT. Information on staff grades and schedules before and after implementing the
      TLA, and cost of contracts to deliver the service were collected. MAIN OUTCOME
      MEASURES: TAT, cost efficiency, and reduction in labor. RESULTS: The
      consolidation of contracts resulted in a reduction of 28.8 million SAR in direct
      costs. Staffing cost was reduced by 1.14 million SAR with less senior staff
      required; there were reductions in staff at both senior and junior level. The
      overall TAT for all tests was reduced by 32% in 2016 (after TLA implementation)
      compared to 2012 (before TLA implementation). The median TAT for random glucose
      tests was reduced by 21% (to 55.7 minutes in 2016 from 70.1 minutes in 2012).
      Evidence of test optimization by exploring the impact of stat tests, auto
      dilutions and reruns on the overall TAT of the TLA is shown by comparing troponin
      T TATs after reclassifying stat tests (in 2016) to routine (in 2017). At the 75th
      percentile, there was a 27% reduction in TAT when comparing August 2016 to March
      2017 with a 19% reduction in median TAT. CONCLUSION: By moving from stat to
      routine assays, the TAT was reduced, which is counter-intuitive. The use of stat
      assays slowed down the performance of the TLA. A careful review of the mix of
      assays should be conducted to maximize performance and to ensure that the system
      delivers what is required. LIMITATIONS: Room for improvement by systematically
      analyzing and reviewing the impact of making minor changes that could have
      significant impact on TAT. CONFLICT OF INTEREST: None.

PMID- 30284991
TI  - Clinicopathologic characteristics andoutcomes of hepatocellular carcinoma
      associated with chronic hepatitis B versus hepatitis C infection.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver malignancy and one
      of the most common cancers worldwide. Few studies in Saudi Arabia have compared
      the clinicopathologic characteristics of HCC caused by hepatitis B virus (HBV)
      versus hepatitis C virus (HCV) and their effect on patient survival and
      prognosis. OBJECTIVES: Identify differences in clinicopathological
      characteristics and outcomes of hepatocellular carcinoma (HCC) caused by HBV
      versus HCV. DESIGN: A retrospective medical records review. SETTING: Tertiary
      medical center in Riyadh. PATIENTS AND METHODS: We included all new cases of HCC
      with underlying HBV and HCV infection diagnosed between January 2013 and
      September 2017 that met inclusion criteria. MAIN OUTCOME MEASURES: Clinical,
      biochemical, pathological and radiological characteristics, and survival
      differences were compared between HCC that developed in HBV- and HCV-infected
      patients. SAMPLE SIZE: Of 253 patients evaluated, 172 patients were included in
      the study. RESULTS: Of the 172 patients, 110 (64%) had HCV-associated HCC and 62
      (36%) had HBV-associated HCC. More patients with HBV infection were males
      (P=.003) and were younger (P=.015) than HCV patients. HCV-infected patients who
      developed HCC had more advanced cirrhosis (P=.048). The prevalence of
      comorbidities and pre-existing cir.rhosis was similar in both groups. Seven
      patients (6.8%) with underlying HCV developed HCC in the absence of cirrhosis.
      Patients with HBV-associated HCC were less likely to meet Milan criteria at
      initial diagnosis than those with HCV-associated HCC (33.9% vs. 52.7%,
      respectively, P=.017). HBV-associated HCC occurred at a more advanced Barcelona
      Clinic Liver Cancer stage. The overall median survival and treatment outcome for
      each modality was comparable. CONCLUSIONS: HBV- and HCV-associated HCC have
      distinct clinical and pathological characteristics, necessitating different
      screening policies to optimize HCC surveillance and management. However, viral
      etiology did not affect the treatment outcome and long-term survival.
      LIMITATIONS: Conducted in a single-center, retrospective and lacks information
      about the use of antiviral treatment. CONFLICT OF INTEREST: None.

PMID- 30284993
TI  - Outcome with topical sirolimus for port wine stain malformations after
      unsatisfactory results with pulse dye laser treatment alone.
AB  - : We used a topical formulation of sirolimus for treating port wine stain (PWS).
      Although pulsed dye laser (PDL) is the current treatment of choice for PWS, fast
      neovascularization after treatment is a major drawback. With PDL therapy there
      has been insufficient improvement and frustrating side effects. The objective was
      to study the efficacy and safety of combining topical sirolimus with PDL as dual
      therapy in managing PWS. We report five PWS cases that were treated with PDL
      initially, followed by 0.5-1% topical sirolimus. With dual therapy there was
      significant improvement over a shorter duration. More published studies of
      topical sirolimus are needed to clarify the role of dual therapy in managing PWS
      associated with capillary malformations. We encourage further prospective and
      comparative studies with a larger sample size. SIMILAR CASES PUBLISHED: 1.

PMID- 30284992
TI  - Dapoxetine for the treatment of premature ejaculation: a meta-analysis of
      randomized controlled trials with trial sequential analysis.
AB  - BACKGROUND: The safety and efficacy of dapoxetine for the treatment of premature
      ejaculation (PE) is still controversial. Thus, we decided to conduct a meta
      analysis using trial sequential analysis (TSA) to determine the sufficiency of
      conclusions. OBJECTIVE: Evaluate the efficacy and safety of dapoxetine in the
      treatment of patients with PE and assess the reliability of the findings. DESIGN:
      Meta-analysis of randomized controlled trials (RCTs). METHODS: Electronic
      databases including PUBMED, EMBASE, Cochrane Library, CNKI and Wanfang data were
      reviewed up to July 2017. RCTs evaluating the efficacy of dapoxetine in patients
      with PE and reporting intravaginal ejaculatory latency time (IELT), patient
      global impression of change (PGIC) and/or adverse events (AEs) were included.
      MAIN OUTCOME MEASURES: Mean differences between trials in efficacy for IELT, and
      risk ratios for PGIC and treatment-emergent AEs. SAMPLE: 8 RCTs. RESULTS: For
      IELT and PGIC, significant effects were found for all doses of dapoxetine versus
      placebo, and similar results were obtained in subgroups of the 30-mg dose versus
      60-mg dose. There were also statistically different dose-related effects on AEs.
      Trial sequential analysis showed that the result of our meta-analysis was
      confirmed and further trials are unnecessary. CONCLUSIONS: The evidence suggests
      that dapoxetine may be a safe and effective drug for patients with PE.
      REGISTRATION: Not registered, no published protocol. CONFLICT OF INTEREST: No
      relationship with manufacturer of drug.

PMID- 30284994
TI  - Rare left-sided presentation of internal jugular vein ectasia in an adult.

PMID- 30284996
TI  - Antitumor and genotoxic effects of lactoferrin in Walker-256 tumor-bearing rats.
AB  - AIM: To investigate the influence of exogenous lactoferrin (LF) on tumor growth,
      energy and lipid metabolism of Walker-256 carcinosarcoma and to assess genotoxic
      effects of LF. MATERIALS AND METHODS: The study was performed on Walker-256 tumor
      bearing rats. Total lipids and phospholipids were determined by thin-layer
      chromatography. Comet assay was used to investigate the genotoxic effects of LF.
      RESULTS: Daily i.p. administrations of exogenous LF at concentrations of 1 mg/kg
      and 10 mg/kg starting from the 4th day after tumor transplantation suppressed
      growth of Walker-256 carcinosarcoma by almost 44%. After treatment with
      recombinant LF in both doses, the phospholipid composition of Walker-256
      carcinosarcoma cells was changed (3-fold increase of phosphatidylethanolamine,
      3.4-fold increase of phosphatidylcholine, and 1.8-fold increase of sphingomyelin,
      while the cardiolipin content decreased by 67%. Exogenous LF was not genotoxic
      for bone marrow cells (as assessed by the ratio of PCE/NCE, number of
      micronuclei) and peripheral blood lymphocytes (percentage of DNA in the tail of a
      comet) in Walker-256 carcinosarcoma-bearing rats. CONCLUSION: Exogenous LF caused
      the inhibition of Walker-256 carcinosarcoma growth and a decrease in the
      microviscosity of plasma cell membranes, and exerted no genotoxicity toward bone
      marrow cells and peripheral blood of experimental animals.

PMID- 30284997
TI  - Influence of metformin, sodium dichloroacetate and their combination on the
      hematological and biochemical blood parameters of rats with gliomas C6.
AB  - BACKGROUND: The efficacy of antimetabolic therapy of malignant neoplasms could
      not be explained solely by the direct mechanisms of action of such energy
      metabolism inhibitors as sodium dichloroacetate (DCA) and metformin (MTF). The
      indirect effects of DCA and MTF on the organs and tissues, which could play
      significant role in the antitumor activity of these agents, have not been
      thoroughly explored. AIM: To investigate the effect of MTF, DCA and their
      combination on the survival of rats with C6 glioma and major haematological and
      biochemical blood parameters. MATERIALS AND METHODS: DCA and MTF were
      administered orally to inbred female rats for 11 days starting from the second
      day after tumor cell transplantation at a total dose of 1.1 and 2.6 g/kg,
      respectively. When combined treatment was used, MTF was administered 3 hours
      after the administration of DCA. The content of lactate and pyruvate in blood
      plasma was determined on the ChemWell(r) 2910 (Combi) automatic analyzer. Blood
      parameters were determined using the Particle Counter PCE-210 automatic
      hematology analyzer. RESULTS: The administration of DCA did not significantly
      affect the life span of rats with C6 glioma. Duration of life of rats, which were
      administered with MTF only, was significantly higher (by 19.1%, p < 0.01).
      Combined administration of DCA + MTF prolonged life span of animals with glioma
      by 50% (p < 0.001). The positive result of antitumor activity of MTF alone and in
      combination with DCA correlated with a decrease in the mean platelet
      volume/platelet count (MPV/PLT) ratio by 75.0% (p < 0.05) compared with tumor
      control. In addition, the expressed antitumor effect of combination therapy with
      DCA and MTF was associated with a decrease (p < 0.05) in glucose and lactate
      levels in blood plasma of rats with C6 glioma by 10% and 41.4%, respectively,
      compared to tumor control. Analysis of blood parameters showed that the growth of
      C6 glioma was accompanied by the development of leukopenia, anemia and
      thrombocytopenia. The introduction of DCA caused the correction of manifestations
      of anemia and leukopenia, but did not affect the level of platelets in the blood
      of animals with glioma. MTF alone and in combination with DCA positively
      influenced the number of white blood cells and caused complete thrombocytopenia
      correction, increasing platelet count by more than 200% (p < 0.001). CONCLUSION:
      The ability of MTF either used alone or in combination with DCA to influence the
      development of C6 glioma which is manifested in an increase in the lifespan of
      rats has been revealed. The most pronounced antitumor effect was recorded against
      the background of the combined use of these agents, which may be due to their
      ability to lower the levels of lactate and glucose in the blood of tumor-bearing
      rats. It is proved that MTF both in monotherapy and in combination with DCA
      provides correction of anemia and thrombocytopenia, which arise at the background
      of glioma C6 growth.

PMID- 30284995
TI  - Anticholinergic Medication Burden in Pediatric Prolonged Critical Illness: A
      Potentially Modifiable Risk Factor for Delirium.
AB  - OBJECTIVES: It is important to describe and understand the prevalence and risk
      factors for the syndrome of delirium in critical illness. Since anticholinergic
      medication may contribute to the development of delirium in the PICU, we have
      sought to quantify anticholinergic medication exposure in patients with prolonged
      admission. We have used Anticholinergic Drug Scale scores to quantify the
      magnitude or extent of this burden. DESIGN: Retrospective cohort study, January
      2011 to December 2015. SETTING: Single academic medical center PICU. PATIENTS:
      Children under 18 years old with a PICU admission of 15 days or longer, requiring
      mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily
      Anticholinergic Drug Scale scores for the first 15 days of admission, in each of
      88 subjects (total of 1,320 PICU days), were collected and assessed in relation
      to demographic data, severity of illness, and medication use. Median
      (interquartile range) of daily Anticholinergic Drug Scale score was 5
      (interquartile range, 3-7). Anticholinergic Drug Scale score was not associated
      with age, sex, medical history, presenting Severity of Illness score, PICU length
      of stay, ventilator hours, or hospital mortality. Medications most frequently
      associated with high Anticholinergic Drug Scale score were low potency
      anticholinergic drugs such as morphine, midazolam, vancomycin, steroids, and
      furosemide, with the exception of ranitidine (Anticholinergic Drug Scale score
      2). Patients receiving high doses of midazolam infusion had significantly higher
      Anticholinergic Drug Scale scores compared with those receiving lower or no
      midazolam dosing. CONCLUSIONS: A high number of medications with anticholinergic
      effects are administered to PICU patients receiving prolonged mechanical
      ventilation. These exposures are much higher than those reported in adult
      intensive care patients. Since anticholinergic drug exposure is associated with
      delirium, further study of this exposure in PICU patients is needed.

PMID- 30284998
TI  - Markers of the epithelial-mesenchymal transition in cells of endometrial
      carcinoma.
AB  - AIM: To study the expression of adhesion markers (E-cadherin, beta-catenin and
      vimentin) associated with epithelial-mesenchymal transition (EMT) and their role
      in progression of endometrial carcinoma (EC). MATERIALS AND METHODS: Expression
      of E-cadherin, beta-catenin and vimentin was studied immunohistochemically in the
      samples of surgical material of 55 EC patients stage I-III. The proliferation
      index was determined by flow cytometry. RESULTS: In the group of vimentin
      negative EC, tumors of low differentiation grade and deep invasion in myometrium
      as well as high expression of E-cadherin and beta-catenin prevailed compared with
      the cases with high expression of vimentin. In addition, in EC with high
      expression of vimentin, an increase in the number of cells with expression of E
      cadherin in the cytoplasm (78.9 +/- 3.6%) and beta-catenin with cytoplasmic
      nuclear localization (73.7 +/- 3.2%) was observed compared with these indices in
      vimentin-negative tumors (45.4 +/- 4.2%, p < 0.001 and 54.5 +/- 2.6%,
      respectively, p < 0.005), which may indicate EMT-associated changes in EC with
      high expression of vimentin. CONCLUSIONS: The progression of the endometrioid
      carcinoma may occur in the setting of various molecular changes, in particular,
      with decreased expression of E-cadherin and beta-catenin and high expression of
      vimentin, or in the absence of vimentin, utilizing other mechanisms of regulation
      of proliferative and metastatic potential.

PMID- 30284999
TI  - Analysis of the 3'UTR region of the NOTCH1 gene in chronic lymphocytic leukemia
      patients.
AB  - : Deregulation of NOTCH1-signalling pathway is common in chronic lymphocytic
      leukemia (CLL). The most of studies are focused on detection of the hotspot
      c.7541_7542delCT NOTCH1 mutations in exon 34, while studies of mutations in the
      3'UTR region are rare. The aims of work were to evaluate the frequencies of
      mutations in the 3'UTR region of the NOTCH1 gene (9:136,495553-136,495994) in
      Ukrainian CLL patients, the distribution of rs3124591 genotypes located in that
      area, and association of NOTCH1 mutations with structure of B-cell receptor.
      MATERIALS AND METHODS: Detection of mutations in the 3'UTR region of the NOTCH1
      was performed by direct sequencing in 87 previously untreated CLL patients (from
      the total group of 237 CLL patients) with unmutated immunoglobulin heavy-chain
      variable (UM IGHV) genes and without mutations in hotspot regions of TP53, SF3B1,
      and exon 34 of NOTCH1 genes. RESULTS: Mutations in the 3'UTR region of the NOTCH1
      were revealed in three of 87 CLL patients (3.4%). Two cases with non-coding
      mutations were related to subset #1 of stereotyped B-cell receptors, and one case
      belonged to stereotyped subset #28a. Analysis with inclusion of 30 UM IGHV cases
      with previously detected c.7544_7545delCT mutations revealed that the frequency
      of UM IGHV genes of I phylogenetic clan (except IGHV1-69) was significantly
      increased, and the frequency of UM IGHV3 and IGHV4 genes, on the contrary, was
      reduced in NOTCH1-mutated cases comparing with NOTCH1-unmutated cases (p = 0.002)
      and the general group (p = 0.013). SNP rs3124591 did not affect the risk of CLL
      and survival parameters of the patients. At the same time, differences were found
      in the frequency of IGHV gene usage and in the structure of HCDR3 in carriers of
      individual genotypes. CONCLUSION: The frequency of NOTCH1 mutations in 3'UTR
      region was low. Our findings confirmed current data on the association between
      the structure of the B-cell receptor and the appearance of NOTCH1 mutations. Some
      features of HCDR3 structure were identified in carriers of TT and CC genotypes of
      rs3124591.

PMID- 30285000
TI  - Yurii Yosypovych Kudryavets (1946-2018).
AB  - Our colleague Professor Yurii Yosypovych Kudryavets, talented scientist
      oncologist, Head of the Department of Experimental Cell Systems of the R.E.
      Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology (IEPOR),
      the NAS of Ukraine, passed away at the age of 71.

PMID- 30285001
TI  - Svitlana Pavlivna Sidorenko (1953-2018).
AB  - Ukrainian oncology suffered a grievous loss. Professor Svitlana Pavlivna
      Sidorenko, a prominent scientist, head of the Department of Molecular and
      Cellular Pathobiology of the R.E. Kavetsky Institute of Experimental Pathology,
      Oncology and Radiobiology of the National Academy of Sciences of Ukraine, a
      Corresponding member of the National Academy of Sciences of Ukraine, after a long
      illness, died on August 26, 2018 at the age of 64.

PMID- 30285002
TI  - A case report of late local relapse of adrenocortical carcinoma 18 years after
      adrenalectomy.
AB  - Adrenocortical cancer is an extremely rare tumor presenting with extensive
      locoregional spread at the time of diagnosis. Due to the diagnostic difficulties
      preoperatively and a lack of effective treatment options, patients have poor
      prognosis. Patients succumb to metastases within a couple of months. Only 20
      cases have been so far reported in the literature with a medium disease-free
      survival up to 2 years. We present a case of a locoregional recurrence of
      adrenocortical cancer 18 years after left adrenalectomy.

PMID- 30285003
TI  - Cytotoxic and genotoxic effects of cadmium sulfide nanoparticles.
AB  - : Cadmium compounds are highly toxic substances characterized by mutagenic,
      genotoxic and carcinogenic effects, and having high cumulative properties.
      Application of cadmium nanoparticles (NPs) in medicine stimulates the study of
      their mechanism of action at the cellular level and at the level of organs and
      systems, determination of biomarkers of their action, particularly in comparison
      with the ionic form. The aim of the study was to compare the features of
      cytotoxic and genotoxic effects of cadmium sulfide (CdS) NPs of different sizes
      on cell cultures of different histogenesis with those of cadmium chloride
      (CdCl2). MATERIALS AND METHODS: In this work, we used cadmium compounds in the
      nanoform: NPs CdS of 4-6 nm and of 9-11 nm in size; and in the ionic form: CdCl2.
      The studies were conducted in vitro in cell lines - IMR-32, NEK-293 and MAEC. To
      count viable cells we compared the results of three basic tests: MTT (methyl
      tetrasolium test), SRB (sulforhodamine B test) and NRU (neutral red uptake test).
      We evaluated the genotoxic effect of the substances studied in vitro using DNA
      comet assay in alkaline conditions. RESULTS: CdS NPs and CdCl2 demonstrated
      pronounced dose-dependent cytotoxic effect in MAEC, NEK-293 and IMR-32 cell
      lines, by impairing membrane permeability, functioning of mitochondria and
      lysosomes, and inhibiting the function of protein synthesis. Cytotoxic effect of
      CdCl2 was the most pronounced, this effect of CdS NPs of 9-11 nm in size being
      the least pronounced. The comet DNA assay in alkaline conditions revealed a
      statistically significant increase in DNA comet index when exposed to CdCl2 and
      CdS NPs in comparison with the negative control, which indicates their genotoxic
      effect. CdS NPs of 4-6 nm in size showed a more pronounced effect in comparison
      with those of 9-11 nm in size. CONCLUSION: Elucidation of mechanisms underlying
      the implementation of toxic effects of cadmium NPs will help in assessing the
      potential risks associated with their use in industry and developing effective
      preventive measures. For instance, when planning in vivo studies for
      toxicological evaluation of nanomaterials and nano-substances containing NPs of
      cadmium, it is necessary to investigate the mutagenic and carcinogenic risks and
      to take into account the high likelihood of neurotoxic and cardiovasotoxic
      effects, along with nephrotoxic effects, since high cytotoxic activity of the
      investigated compounds of cadmium was detected on the cells of the MAEC line
      (endothelial origin) and IMR-32 (neuronal origin).

PMID- 30285004
TI  - ABO blood group and the risk of lung cancer in Greek adults: a case - control
      study.
AB  - AIM: The present study aimed to investigate any possible association between ABO
      blood groups and lung cancer. MATERIALS AND METHODS: The study was conducted on
      122 lung cancer patients and 1,255 matched-healthy individuals that were reviewed
      retrospectively. Chi-square and logistic regression models were used for
      statistical analysis. RESULTS: No significant difference between lung cancer
      patients and the control group was recorded regarding ABO blood types and the
      risk of lung cancer (p = 0.055, OR = 0.79, 95% CI 0.61-1.03). Male gender (p =
      0.006, OR = 2.08, 95% CI 1.24-3.49) and smoking (p = 0.000, OR = 3.13, 95% CI
      1.72-5.69) were significantly associated with the risk of lung cancer.
      CONCLUSION: No association between ABO blood types and the risk of lung cancer
      was observed.

PMID- 30285005
TI  - The impact of morphine treatment on bladder cancer cell proliferation and
      apoptosis: in vitro studies.
AB  - AIM: The aim of this study was to determine the effect of morphine on bladder
      cancer cell proliferation and apoptosis in vitro. MATERIALS AND METHODS: MTT
      assay was used to measure percentage growth of RT-112 human bladder cancer cells
      after 72 hours of morphine/morphine + naloxone treatment. Expression of u-opioid
      receptors was assessed by Western blot and finally, apoptotic assay with
      CellEvent Caspase-3/7 Green Detection Reagent was carried out using confocal
      microscopy. RESULTS: The MTT assays showed that morphine increased RT-112 cell
      growth. Naloxone inhibited this growth enhancing effect. Western blot analysis
      regarding u-opioid receptor expression in RT-112 cells remains inconclusive.
      Morphine was also found to decrease the rate of apoptosis of RT-112 cells, an
      effect which naloxone inhibited. CONCLUSIONS: This study provides evidence that
      morphine, at clinically relevant doses, causes RT-112 bladder cancer cell
      proliferation, possibly opioid receptor mediated and at least some of this effect
      might be due to decreased apoptosis. Clinically, this suggests that in patients
      with bladder cancer, managing pain with morphine might have detrimental
      consequences on patient outcomes and alternative pain relief should be considered
      if possible.

PMID- 30285006
TI  - Analysis of the survival of patients with breast cancer depending on age,
      molecular subtype of tumor and metabolic syndrome.
AB  - AIM: To analyze the survival of patients with breast cancer (BC) depending on
      age, molecular subtype of the tumor and the presence of metabolic syndrome.
      PATIENTS AND METHODS: We have analyzed the results of examination and treatment
      of 202 patients with BC of stages I-III. The patients were distributed by age
      into 2 groups. The group 1 included 86 elderly patients (from 65 to 84 years
      old), the group 2 - 116 younger patients (from 32 to 64 years). An overall 1-, 3-
      and 5-year survival rates of the treated patients were assessed. The significance
      of factors influencing the overall survival (OS) of patients with BC was
      determined using the methods of statistical analysis. RESULTS: Molecular subtype
      of BC significantly affects survival rates: in a case of a luminal B subtype the
      5-year OS was 71.6 vs 80% (p < 0.05) in groups 1 and 2, respectively while in a
      case of a basal-like subtype it was 60.2% and 71.6% (p < 0.05). The presence of
      metabolic syndrome significantly reduced the 5-year OS (up to 70.7% and 80.6%, p
      < 0.05 in groups 1 and 2, respectively). CONCLUSION: The OS is lower in elderly
      patients with BC compared with younger patients, especially in those who suffer
      from metabolic syndrome.

PMID- 30285007
TI  - Paraneoplastic syndrome in lung cancer.
AB  - AIM: To study the nature of different variants of paraneoplastic syndrome (PNPS)
      in lung cancer, taking into account the features of the tumorous process and the
      complications of radiochemotherapy. PATIENTS AND METHODS: We performed an
      analysis of the data of 1,669 patients with lung cancer aged between 24 and 87
      years, among whom there were 89% of men and 11% of women. The ratio of small cell
      and non-small-cell histological variants of the lung cancer was 1: 4, IB, IIA,
      IIB, IIIA, IIIB and IV stages of cancer - 1:2:6:58:43:57. RESULTS: PNPS developed
      in 16% of the lung cancer patients, in these patients we have detected a marked
      increase in the disease incidence in women, the peripheral form of the tumor, the
      apical variant of Pancoast - Tobias and adenocarcinoma, but no cases of the
      median lower localization of the tumor. The number of the upper lobar pathology
      was decreased, while the severity of the cancer was significantly greater, which
      more often occurred with exudative pleurisy, germination of the tumor into the
      chest wall and compression of the upper vena cava. The 21 components of PNPS
      pathology were established. We distributed them conditionally into the
      musculoskeletal system lesions, variants of skin vasculitis and autoimmune
      processes, the nature of which depended on the localization and course of the
      tumorous process, its histological variation and severity of the course.
      Moreover, PNPS negatively affected the development of radiochemotherapy
      complications and worsened survival rate. CONCLUSIONS: The course of PNPS in lung
      cancer is highly diverse, being a risk factor for a severe tumorous process that
      worsens the survival of patients.

PMID- 30285008
TI  - Determination of oxygen perfusion in the area of radiation-induced fibrosis of
      the skin in patients with breast cancer and its role in pathogenesis of late
      radiation injury.
AB  - AIM: Late radiation injury in the form of radiation-induced fibrosis (RIF) is one
      of the many complications of radiation therapy. The aim was to evaluate oxygen
      perfusion in the skin in the area of late radiation injury manifested as RIF in
      patients with breast cancer. MATERIALS AND METHODS: Based on our first-hand
      experience in treating late radiation injures of soft tissues in patients with
      breast cancer, we measured oxygen perfusion of the skin (tsrO2) in the area of
      late radiation injury using a transcutaneous monitor (oximeter) TCM 400
      (Radiometer, Denmark). RESULTS: Partial oxygen pressure tcpO2 in the RIF area in
      patients with breast cancer didn't show any significant decrease compared to
      healthy tissue. Mean value of partial oxygen pressure tcpO2 in the RIF area was
      42.650 +/- 9.178 mmHg, in the healthy tissue it was 45.180 +/- 8.025 mmHg.
      Maximal difference in tcpO2 between the damaged and healthy tissue was 30 mmHg.
      CONCLUSIONS: Results of the study suggest that there's no significant difference
      between oxygen perfusion (tcpO2) in the area of RIF and healthy tissue.

PMID- 30285009
TI  - Effects of exogenous lactoferrin on phenotypic profile and invasiveness of human
      prostate cancer cells (DU145 and LNCaP) in vitro.
AB  - AIM: To investigate the biological effects of exogenous lactoferrin (LF) on
      phenotypic profile and invasiveness of human prostate cancer (PC) cells in vitro.
      MATERIALS AND METHODS: Human PC cell lines (LNCaP, DU-145) were cultured with an
      exogenous LF at a dose corresponding to IC30. The expression levels of steroid
      hormone receptors (androgen receptor, estrogen receptor, progesterone receptor),
      Her2/neu, Ki-67, E- and N-cadherin, were monitored by immunohistochemical
      analysis. The levels of miRNAs were assessed using q-PCR. The invasive activity
      of the cells was examined in a standard invasion test. RESULTS: Exogenous LF
      reduced expression of steroid hormone receptors (ERalpha and PR) and Ki-67 in
      both PC cell lines. The expression of E-cadherin increased significantly in LF
      treated DU-145 cells. Also, we established the decrease in invasive activity upon
      LF treatment by 40% and 30% in DU-145 and LNCaP cells, respectively. In DU-145
      cells, incubation with exogenous LF resulted in an increase in the expression of
      oncosuppressive (miR-133a and miR-200b) miRNAs. CONCLUSIONS: Exogenous LF causes
      the changes in phenotypic characteristics of PC cells and levels of oncogenic and
      oncosuppressive miRNAs involved in the regulation of key cellular processes.

PMID- 30285010
TI  - Different morphological structures of breast tumors demonstrate individual drug
      resistance gene expression profiles.
AB  - AIM: To identify gene expression profiles involved in drug resistance of
      different morphological structures (tubular, alveolar, solid, trabecular, and
      discrete) presented in breast cancer. MATERIAL AND METHODS: Ten patients with
      luminal breast cancer have been included. A laser microdissection-assisted
      microarrays and qRT-PCR were used to perform whole-transcriptome profiling of
      different morphological structures, to select differentially expressed drug
      response genes, and to validate their expression. RESULTS: We found 27
      differentially expressed genes (p < 0.05) encoding drug uptake (SLC1A3, SLC23A2,
      etc.) and efflux (ABCC1, ABCG1, etc.) transporters, drug targets (TOP2A, TYMS,
      and Tubb3), and proteins that are involved in drug detoxification (NAT1 and
      ALDH1B1), cell cycle progression (CCND1, AKT1, etc.), apoptosis (CASP3, TXN2,
      etc.), and DNA repair (BRCA1 and USP11). Each type of structures showed an
      individual gene expression profile related to resistance and sensitivity to
      anticancer drugs. However, most of the genes (19/27; p < 0.05) were expressed in
      alveolar structures. Functional enrichment analysis showed that drug resistance
      is significantly associated with alveolar structures. Other structures
      demonstrated the similar number (10-13 out of 27) of expressed genes; however,
      the spectrum of resistance and sensitivity to different anticancer drugs varied.
      CONCLUSION: Different morphological structures of breast cancer show individual
      expression of drug resistance genes.

PMID- 30285012
TI  - Comparative histochemical evaluation of mucins expression in fetal esophagus and
      adenocarcinomas of the gastroesophageal junction.
AB  - AIM: To study and compare the expression patterns of mucins in the fetal
      gastroesophageal junction (GEJ) region and adenocarcinomas of the GEJ in adults
      using histochemical method. MATERIAL AND METHODS: To reveal the expression of
      different mucins, tissue sections from formalin-fixed paraffin-embedded tissue
      blocks of fetal GEJ and carcinomas of GEJ were stained by the following
      histological stains: hematoxylin and eosin, periodic acid-Schiff (PAS), alcian
      blue (AB), pH 2.5, combined AB-PAS, and combined AB-Aldehyde Fuchsin (AB/AF).
      RESULTS: Expression of mucins within the developing fetal GEJ has been
      demonstrated (gestational age 5-38 weeks). We studied histochemical features of
      neoplastic cells in carcinomas of GEJ from 90 adult patients. The results showed
      that in gastric type expression of neutral mucins dominated especially in well
      differentiated (G1) adenocarcinomas and corresponded to the last three months of
      GEJ development, while in the intestinal and mixed type significant acid mucins
      expression was detected in moderate (G2) and poorly (G3) differentiated
      adenocarcinomas and corresponded to 17-25 weeks of GA. No significant coincidence
      in mucins expression was observed in signet ring cell carcinomas in relation to
      GA. CONCLUSION: Our data suggest that decrease of neutral mucins level can be
      considered reliable phenotypic marker of poor prognosis of GEJ adenocarcinomas.
      Study of the developmental expression of mucin genes may improve understanding of
      the malignant transformation of esophageal tissue.

PMID- 30285011
TI  - Role of dendrimers in advanced drug delivery and biomedical applications: a
      review.
AB  - AIM: Dendrimers dendritic structural design holds vast promises, predominantly
      for drug delivery, owing to their unique properties. Dendritic architecture is
      widespread topology found in nature and offers development of specific properties
      of chemical substances. Dendrimers are an ideal delivery vehicle candidate for
      open study of the effects of polymer size, charge, and composition on
      biologically relevant properties such as lipid bilayer interactions,
      cytotoxicity, bio-distribution, internalization, blood plasma retention time, and
      filtration. This article reviews role of dendrimers in advanced drug delivery and
      biomedical applications.

PMID- 30285013
TI  - Sterically demanding methoxy and methyl groups in ruthenium complexes lead to
      enhanced quantum yields for blue light triggered photodissociation.
AB  - Ruthenium complexes containing a sterically congested metal center can serve as
      light activated prodrugs through photo-activated chemotherapy (PACT). In this
      work, we modified PACT agents containing 6,6'-dihydroxybipyridine (6,6'-dhbp)
      (Papish et al., Inorg. Chem., 2017, 56, 7519) by replacing it with a sterically
      bulky isoelectronic ligand, 6,6'-dimethoxybipyridine (6,6'-dmbp). The resulting
      complexes, [(phen)2Ru(6,6'-dmbp)]Cl2 (2OMe, phen = 1,10-phenanthroline) and
      [(dop)2Ru(6,6'-dmbp)]Cl2 (3OMe, dop = 2,3-dihydro-[1,4]dioxino[2,3
      f][1,10]phenanthroline), have been fully characterized and display enhanced
      quantum yields for blue light triggered photodissociation of 0.024(6) and
      0.0030(2), respectively. We have also synthesized 4OH = [(dmphen)2Ru(4,4'
      dhbp)]Cl2 wherein dmphen = 2,9-dimethyl-1,10-phenanthroline and 4,4'-dhbp = 4,4'
      dihydroxybipyridine. These ligands enhance steric bulk near the metal center and
      move the hydroxy groups further from the metal center, respectively. Complex 4OH
      displays a relatively low quantum yield of 0.0014(2). All of the new complexes
      (2OMe, 3OMe, 4OH) were tested in breast cancer cells (MDA-MB-231) and were non
      toxic (IC50 > 100 MUM). This has been interpreted in terms of unfavorable
      log(Do/w) values and furthermore photodissociation alone is insufficient for
      cytotoxicity. We also report the crystal structures of 4OH and 2OMe, the
      thermodynamic acidity of complex 4OH, and the redox potentials for all new
      complexes.

PMID- 30285015
TI  - Ru(ii)-Peptide bioconjugates with the cppH linker (cppH = 2-(2'
      pyridyl)pyrimidine-4-carboxylic acid): synthesis, structural characterization,
      and different stereochemical features between organic and aqueous solvents.
AB  - Three new Ru(ii) bioconjugates with the C-terminal hexapeptide sequence of
      neurotensin, RRPYIL, namely trans,cis-RuCl2(CO)2(cppH-RRPYIL-kappaNp) (7),
      [Ru([9]aneS3)(cppH-RRPYIL-kappaNp)(PTA)](Cl)2 (8), and [Ru([9]aneS3)Cl(cppH
      RRPYIL-kappaNp)]Cl (11), where cppH is the asymmetric linker 2-(2'
      pyridyl)pyrimidine-4-carboxylic acid, were prepared in pure form and structurally
      characterized in solution. The cppH linker is capable of forming stereoisomers
      (i.e. linkage isomers), depending on whether the nitrogen atom ortho (No) or para
      (Np) to the carboxylate on C4 in the pyrimidine ring binds the metal ion. Thus,
      one of the aims of this work was to obtain pairs of stereoisomeric conjugates and
      investigate their biological (anticancer, antibacterial) activity. A thorough NMR
      characterization clearly indicated that in all cases exclusively Np conjugates
      were obtained in pure form. In addition, the NMR studies showed that, whereas in
      DMSO-d6 each conjugate exists as a single species, in D2O two (7) or even three
      if not four (8 and 11) very similar stable species form (each one corresponding
      to an individual compound). Similar results were observed for the cppH-RRPYIL
      ligand alone. Overall, the NMR findings are consistent with the occurrence of a
      strong intramolecular stacking interaction between the phenol ring of tyrosine
      and the pyridyl ring of cppH. Such stacking interactions between aromatic rings
      are expected to be stronger in water. This interaction leads to two
      stereoisomeric species in the free cppH-RRPYIL ligand and in the bioconjugate 7,
      and is somehow modulated by the less symmetrical Ru coordination environments in
      8 and 11, affording three to four very similar species.

PMID- 30285014
TI  - Chemical micromotors self-assemble and self-propel by spontaneous symmetry
      breaking.
AB  - Self-propelling chemical motors have thus far required the fabrication of Janus
      particles with an asymmetric catalyst distribution. Here, we demonstrate that
      simple, isotropic colloids can spontaneously assemble to yield dimer motors that
      self-propel. In a mixture of isotropic titanium dioxide colloids with photo
      chemical catalytic activity and passive silica colloids, light illumination
      causes diffusiophoretic attractions between the active and passive particles and
      leads to the formation of dimers. The dimers constitute a symmetry-broken motor,
      whose dynamics can be fully controlled by the illumination conditions. Computer
      simulations reproduce the dynamics of the colloids and are in good agreement with
      experiments. The current work presents a simple route to obtain large numbers of
      self-propelling chemical motors from a dispersion of spherically symmetric
      colloids through spontaneous symmetry breaking.

PMID- 30285016
TI  - Symmetry-adapted perturbation theory potential for the adenine dimer.
AB  - A new intermolecular interaction potential for the adenine dimer has been
      developed with the help of a combination of symmetry-adapted perturbation theory
      and density functional theory (DFT-SAPT). Supermolecular intermolecular
      interaction energy computations on hydrogen-bonded and stacked adenine dimers at
      B3LYP-D, MP2, SCS-MP2, SCS-MI-MP2 and CCSD(T) levels showed that DFT-SAPT is in a
      very good agreement with CCSD(T). The developed ab initio intermolecular
      potential has been used to predict the cluster structure of adenine dimers,
      trimers and tetramers. These global cluster optimizations reproduced adenine
      dimers reported in the literature and moreover new low-energy structures were
      also located. For trimers and tetramers, new hydrogen-bonded and stacked low
      energy structures have also been found. The current findings suggest that the new
      ab initio potential can further be exploited to reveal the structure and energy
      of much larger supramolecular adenine clusters.

PMID- 30285017
TI  - Reviving old protecting group chemistry for site-selective peptide-protein
      conjugation.
AB  - Methodologies to conjugate proteins to property-enhancing entities are highly
      sought after. We report a remarkably simple strategy for conjugating proteins
      bearing accessible cysteines to unprotected peptides containing a Cys(Scm)
      protecting group, which is introduced on-resin via a Cys(Acm) building block. The
      peptides employed for this proof of principle study are highly varied and
      structurally diverse, and undergo multiple on-resin decoration steps prior to
      conjugation. The methodology was applied to three different proteins, and proved
      to be efficient and site-selective. This twist on protecting group chemistry has
      led to a novel and generally applicable strategy for crossed-disulfide formation
      between proteins and peptides.

PMID- 30285018
TI  - Correction: Engineered hydrogen-bonded polymer multilayers: from assembly to
      biomedical applications.
AB  - Correction for 'Engineered hydrogen-bonded polymer multilayers: from assembly to
      biomedical applications' by Georgina K. Such et al., Chem. Soc. Rev., 2011, 40,
      19-29.

PMID- 30285019
TI  - Forcing the 'lazy' protons to work.
AB  - The combination of cross-polarization (CP) with flip-back (FB) pulse has enabled
      in NMR the enhancement of 13C sensitivity and the decrease of the recycling delay
      at both moderate and fast magic-angle spinning (MAS) frequencies. However, only
      continuous-wave (CW) decoupling is presently compatible with FB-pulse (FB-CW),
      and depending on the CW radio-frequency (rf) field, either an insignificant
      sensitivity gain or an acquisition time-dependent gain and a low 13C resolution
      are obtained. In this study, we propose a new FB-pulse method in which radio
      frequency-driven recoupling (RFDR) is used as the 1H-13C decoupling scheme to
      overcome these drawbacks. The performances of FB-RFDR in terms of decoupling
      efficiency and sensitivity gain are tested on both natural abundance (NA) and
      uniformly 13C-15N labeled l-histidine.HCl.H2O (Hist) samples at a MAS frequency
      of nuR = 70 kHz. The results show the superiority of RFDR over the CW decoupling
      with respect to these criteria. Importantly, they reveal that the sensitivity
      gain offered by FB-RFDR is nearly independent of the decoupling/acquisition
      duration. The application of FB-RFDR on NA-Hist and sucrose yields a sensitivity
      gain between 60 and 100% compared to conventional FB-CW and CPMAS-SPINAL
      experiments. Moreover, we compare the 13C sensitivities of NA-Hist obtained by
      our 1D FB-RFDR method and 2D 1H-{13C} double-CP acquisition. Both methods provide
      similar 13C sensitivity and are complementary. Indeed, the 2D method has the
      advantage of also providing the 1H-13C spatial proximities, but its sensitivity
      for quaternary carbons is limited; whereas our 1D FB-RFDR method is more
      independent of the type of carbon, and can provide a 13C 1D spectrum in a shorter
      experimental time. We also test the feasibility of FB-RFDR at a moderate
      frequency of nuR = 20 kHz, but the experimental results demonstrate a poor
      resolution as well as a negligible sensitivity gain.

PMID- 30285020
TI  - Applications of crystal structure prediction - organic molecular structures:
      general discussion.

PMID- 30285022
TI  - An atomically precise all-tert-butylethynide-protected Ag51 superatom nanocluster
      with color tunability.
AB  - The tert-butylethynide ligand has been employed to construct an atomically
      precise all-tert-butylethynide-protected silver superatom nanocluster,
      Ag51(tBuC[triple bond, length as m-dash]C)32 (hereafter denoted as Ag51). The
      identity of Ag51 is confirmed by high resolution ESI-MS and elemental analysis.
      Single crystal X-ray analysis revealed that the structure of Ag51 features a
      three-shell arrangement, Ag@Ag8/Ag6@Ag36@C24/C8. Ag51 exhibits a strong
      solvatochromic effect, and the emissions are strongly dependent on the solvent
      polarity and are tunable from blue to red by changing the solvent from less polar
      dichloromethane to highly polar methanol.

PMID- 30285025
TI  - l-Dopa and dopamine conjugated naphthalenediimides modulate amyloid beta
      toxicity.
AB  - The process of protein misfolding and aggregation to form neurotoxic species is
      strongly implicated in most of the neurodegenerative disorders. In particular,
      amyloid beta (Abeta) misfolding and aggregation is central to pathophysiological
      processes of Alzheimer's disease. The development of aggregation modulators has
      enormous implications in the discovery of effective therapeutic agents for
      Alzheimer's disease. Herein, we report the design and synthesis of a series of
      natural amino acid, l-dopa and dopamine appended derivatives of
      naphthalenediimide (NDI) to identify efficient aggregation modulators.
      Furthermore, the molecular docking studies revealed the possible binding sites
      and binding mode of NDI-conjugates to Abeta aggregates. Among the designed NDI
      conjugates, l-dopa and dopamine derivatives (NLD and NDP, respectively) showed
      excellent aggregation modulation efficiency (inhibition and dissolution), as
      shown by the thioflavin T (ThT) binding assays, dot blot analysis and in cellulo
      studies. The docking results from in silico studies are in good agreement with
      the experimental data. In addition to their significant modulation efficiency
      towards Abeta aggregation, NLD and NDP possess antioxidant activity conducive to
      the development of disease-modifying therapeutic agents for the treatment of
      Alzheimer's disease.

PMID- 30285028
TI  - Variation in the Heritability of Child Body Mass Index by Obesogenic Home
      Environment.
AB  - Importance: The early obesogenic home environment is consistently identified as a
      key influence on child weight trajectories, but little research has examined the
      mechanisms of that influence. Such research is essential for the effective
      prevention and treatment of overweight and obesity. Objective: To test behavioral
      susceptibility theory's hypothesis that the heritability of body mass index (BMI)
      is higher among children who live in more obesogenic home environments. Design,
      Setting, and Participants: This study was a gene-environment interaction twin
      study that used cross-sectional data from 925 families (1850 twins) in the Gemini
      cohort (a population-based prospective cohort of twins born in England and Wales
      between March and December 2007). Data were analyzed from July to October 2013
      and in June 2018. Exposures: Parents completed the Home Environment Interview, a
      comprehensive measure of the obesogenic home environment in early childhood.
      Three standardized composite scores were created to capture food, physical
      activity, and media-related influences in the home; these were summed to create
      an overall obesogenic risk score. The 4 composite scores were split on the mean,
      reflecting higher-risk and lower-risk home environments. Main Outcomes and
      Measures: Quantitative genetic model fitting was used to estimate heritability of
      age-adjusted and sex-adjusted BMI (BMI SD score, estimated using British 1990
      growth reference data) for children living in lower-risk and higher-risk home
      environments. Results: Among 1850 twins (915 [49.5%] male and 935 [50.5%] female;
      mean [SD] age, 4.1 [0.4] years), the heritability of BMI SD score was
      significantly higher among children living in overall higher-risk home
      environments (86%; 95% CI, 68%-89%) compared with those living in overall lower
      risk home environments (39%; 95% CI, 21%-57%). The findings were similar when
      examining the heritability of BMI in the separate food and physical activity
      environment domains. Conclusions and Relevance: These findings support the
      hypothesis that obesity-related genes are more strongly associated with BMI in
      more obesogenic home environments. Modifying the early home environment to
      prevent weight gain may be particularly important for children genetically at
      risk for obesity.

PMID- 30285029
TI  - Dose-Dependent Associations Between Sleep Duration and Unsafe Behaviors Among US
      High School Students.

PMID- 30285030
TI  - Thresholds for Valve Replacement in Asymptomatic Patients With Aortic Stenosis.

PMID- 30285031
TI  - Optimizing the Detection of Left Ventricular Thrombus Following Acute Myocardial
      Infarction in the Current Era-Reply.

PMID- 30285032
TI  - Optimizing the Detection of Left Ventricular Thrombus Following Acute Myocardial
      Infarction in the Current Era.

PMID- 30285033
TI  - Need for Automated Interactive Genomic Interpretation and Ongoing Reanalysis.

PMID- 30285034
TI  - Infant and Youth Mortality Trends by Race/Ethnicity and Cause of Death in the
      United States.
AB  - Importance: The United States has higher infant and youth mortality rates than
      other high-income countries, with striking disparities by racial/ethnic group.
      Understanding changing trends by age and race/ethnicity for leading causes of
      death is imperative for focused intervention. Objective: To estimate trends in US
      infant and youth mortality rates from 1999 to 2015 by age group and
      race/ethnicity, identify leading causes of death, and compare mortality rates
      with Canada and England/Wales. Design, Setting, and Participants: This
      descriptive study analyzed death certificate data from the US National Center for
      Health Statistics, Statistics Canada, and the UK Office of National Statistics
      for all deaths among individuals younger than 25 years. The study took place from
      January 1, 1999, to December 31, 2015, and analyses started in September 2017.
      Exposures: Race/ethnicity. Main Outcomes and Measures: Average annual percent
      changes in mortality rates from 1999 to 2015 and absolute rate change between
      1999 to 2002 and 2012 to 2015 for each age group, race/ethnicity, and cause of
      death. Results: Among individuals from birth to age 24 years, 1 169 537 deaths
      occurred in the United States, 80 540 in Canada, and 121 183 in England/Wales
      from 1999 to 2015. In the United States, 64% of deaths occurred in male
      individuals and 52.6% occurred in white individuals (25.1% deaths occurred in
      black individuals and 17.9% in Latino individuals). All-cause mortality declined
      for all age groups (infants younger than 1 year [38.5% of deaths], children aged
      1-9 years [10.6%], early adolescents aged 10-14 years [5%], late adolescents aged
      15-19 years [17.7%], and young adults aged 20-24 years [28.1%]) in the United
      States, Canada, and England/Wales from 1999 to 2015. However, rates were highest
      in the United States. Within the United States, annual declines in all-cause
      mortality rates occurred among all age groups of black, Latino, and white
      individuals, except for white individuals aged 20 to 24 years, whose rates
      remained stable. Mortality rates declined across most major causes of death from
      1999 to 2002 and 2012 to 2015, with notable declines observed for sudden infant
      death syndrome, unintentional injury death, and homicides. Among infants,
      unintentional suffocation and strangulation in bed increased (difference between
      2012-2015 and 1999-2002 range, 6.11-29.03 per 100 000). Further, suicide rates
      among Latino and white individuals aged 10 to 24 years (range, 0.21-2.63 per 100
      000) and black individuals aged 10 to 19 years (range, 0.10-0.45 per 100 000)
      increased, as did unintentional injury deaths in white young adults (0.79 per 100
      000). The rise in unintentional injury deaths is attributed to increases in drug
      poisonings and was also observed in black and Latino young adults. Conclusions
      and Relevance: Mortality rates in the United States have generally declined for
      infants and youths from 1999 to 2015 owing to reductions in sudden infant death
      syndrome, unintentional injury death, and homicides. However, US mortality rates
      remain higher than Canada and England/Wales, with particularly elevated rates
      among black and American Indian/Alaskan Native youth. Further, there is a
      concerning increase in suicide and drug poisoning death rates among US
      adolescents and young adults.

PMID- 30285035
TI  - Disclosures Can Always Be Improved.

PMID- 30285036
TI  - Healthy Homes and Obesogenic Genes in Young Children: Rigorous Behavioral Theory
      and Measurement and the Detection of Gene-Environment Interactions.

PMID- 30285037
TI  - Global Orbital Infarction Syndrome After a Carotid Artery Dissection.

PMID- 30285038
TI  - In Screening for Colorectal Cancer, Is the FIT Right for the Right Side of the
      Colon?

PMID- 30285039
TI  - Caution Advised for Readers of Comments Related to Retracted Article.

PMID- 30285040
TI  - Disclosures Can Always Be Improved-Reply.

PMID- 30285041
TI  - Association of Risk for Venous Thromboembolism With Use of Low-Dose Extended- and
      Continuous-Cycle Combined Oral Contraceptives: A Safety Study Using the Sentinel
      Distributed Database.
AB  - Importance: Continuous/extended cyclic estrogen use (84/7 or 365/0 days cycles)
      in combined oral contraceptives (COCs) could potentially expose women to an
      increased cumulative dose of estrogen, compared with traditional cyclic regimens
      (21/7 days cycle), and may increase the risk for venous thromboembolism (VTE).
      Objective: To determine, while holding the progestogen type constant, whether the
      risk for VTE is higher with use of continuous/extended COCs than with cyclic COCs
      among women who initiated a COC containing ethinyl estradiol and levonorgestrel.
      Design, Setting, and Participants: Incident user retrospective cohort study of
      primarily commercially insured US population identified from the Sentinel
      Distributed Database. Participants were women aged 18 to 50 years at the time of
      initiating a study COC between May 2007 and September 2015. Using a propensity
      score approach and Cox proportional hazards regression models, we estimated the
      hazard ratios of VTE overall and separately by ethinyl estradiol dose and age
      groups. Exposures: Initiation of continuous/extended or traditional cyclic COCs
      containing ethinyl estradiol or levonorgestrel of any dose. Main Outcomes and
      Measures: First VTE hospitalization that occurred during the study follow-up,
      identified by an inpatient International Classification of Diseases, Ninth
      Revision, Clinical Modification diagnosis code of 415.1, 415.1x, 453, 453.x, or
      453.xx. Results: We identified 210 691 initiators of continuous/extended COCs
      (mean [SD] age, 30.4 [8.6] years) and 522 316 initiators of cyclic COCs (mean
      [SD] age, 28.8 [8.3] years), with a mean of 0.7 person-years at risk among
      continuous/extended and cyclic users. Baseline cardiovascular and metabolic
      conditions (7.2% vs 4.7%), gynecological conditions (39.7% vs 32.3%), and health
      services utilization were slightly higher among continuous/extended cyclic than
      cyclic COC users. Propensity score matching decreased the hazard ratio estimates
      from 1.84 (95% CI, 1.53-2.21) to 1.32 (95% CI, 1.07-1.64) for continuous/extended
      use compared with cyclic COC use. The absolute risk difference (0.27 per 1000
      persons) and the incidence rate difference (0.35 cases per 1000 person-years
      [1.44 vs 1.09 cases per 1000 person-years]) between the 2 propensity score
      matched cohorts remained low, which may not translate into a clinically
      significant risk differences between cyclic and noncyclic estrogen use.
      Conclusions and Relevance: Holding the progestogen type constant
      (levonorgestrel), we observed a slightly elevated VTE risk in association with
      continuous/extended COC use when compared with cyclic COC use. However, due to
      the small absolute risk difference and potential residual confounding, our
      findings did not show strong evidence supporting a VTE risk difference between
      continuous/extended and cyclic COC use.

PMID- 30285042
TI  - Effect of Increased Daily Water Intake in Premenopausal Women With Recurrent
      Urinary Tract Infections: A Randomized Clinical Trial.
AB  - Importance: Increased hydration is often recommended as a preventive measure for
      women with recurrent cystitis, but supportive data are sparse. Objective: To
      assess the efficacy of increased daily water intake on the frequency of recurrent
      cystitis in premenopausal women. Design, Setting, and Participants: Randomized,
      open-label, controlled, 12-month trial at a clinical research center (years 2013
      2016). Among 163 healthy women with recurrent cystitis (>=3 episodes in past
      year) drinking less than 1.5 L of fluid daily assessed for eligibility, 23 were
      excluded and 140 assigned to water or control group. Assessments of daily fluid
      intake, urinary hydration, and cystitis symptoms were performed at baseline, 6-
      and 12-month visits, and monthly telephone calls. Interventions: Participants
      were randomly assigned to drink, in addition to their usual fluid intake, 1.5 L
      of water daily (water group) or no additional fluids (control group) for 12
      months. Main Outcomes and Measures: Primary outcome measure was frequency of
      recurrent cystitis over 12 months. Secondary outcomes were number of
      antimicrobial regimens used, mean time interval between cystitis episodes, and 24
      hour urinary hydration measurements. Results: The mean (SD) age of the 140
      participants was 35.7 (8.4) years, and the mean (SD) number of cystitis episodes
      in the previous year was 3.3 (0.6). During the 12-month study period, the mean
      (SD) number of cystitis episodes was 1.7 (95% CI, 1.5-1.8) in the water group
      compared with 3.2 (95% CI, 3.0-3.4) in the control group, with a difference in
      means of 1.5 (95% CI, 1.2-1.8; P < .001). Overall, there were 327 cystitis
      episodes, 111 in the water group and 216 in the control group. The mean number of
      antimicrobial regimens used to treat cystitis episodes was 1.9 (95% CI, 1.7-2.2)
      and 3.6 (95% CI, 3.3-4.0), respectively, with a difference in means of 1.7 (95%
      CI, 1.3-2.1; P < .001). The mean time interval between cystitis episodes was
      142.8 (95% CI, 127.4-160.1) and 84.4 (95% CI, 75.4-94.5) days, respectively, with
      a difference in means of 58.4 (95% CI, 39.4-77.4; P < .001). Between baseline and
      12 months, participants in the water group, compared with those in the control
      group, had increased mean (SD) urine volume (1.4 [0.04] vs 0.1 [0.04] L; P <
      .001) and voids (2.4 [0.2] vs -0.1 [0.2]; P < .001) and decreased urine
      osmolality (-402.8 [19.6] vs -24.0 [19.5] mOsm/kg; P < .001). Conclusions and
      Relevance: Increased water intake is an effective antimicrobial-sparing strategy
      to prevent recurrent cystitis in premenopausal women at high risk for recurrence
      who drink low volumes of fluid daily. Trial Registration: ClinicalTrials.gov
      identifier: NCT02444975.

PMID- 30285043
TI  - Introducing "Images in Dermatology".

PMID- 30285044
TI  - Challenges in Defining Inappropriate Medication Use in Parkinson Disease
      Dementia.

PMID- 30285045
TI  - Exercise for Leg Ulcers: "Working Out" the Nature of Venous Ulcers.

PMID- 30285046
TI  - Ten Principles for More Conservative, Care-Full Diagnosis.

PMID- 30285047
TI  - Patterns of Dementia Treatment and Frank Prescribing Errors in Older Adults With
      Parkinson Disease.
AB  - Importance: Dementia is common in Parkinson disease, but few data exist on
      dementia treatment patterns or the concurrent use of acetylcholinesterase
      inhibitors (ACHEIs) and anticholinergic medications, a frank prescribing error.
      Objectives: To describe dementia treatment patterns, and to determine the extent
      to which the concurrent use of ACHEIs and drugs with strong anticholinergic
      activity occurs among individuals with Parkinson disease in the United States.
      Design, Setting, and Participants: This cross-sectional analysis included adult
      Medicare beneficiaries (aged 65 years or older) with Parkinson disease diagnosis
      with 12 consecutive months of inpatient, outpatient, and prescription drug
      coverage from January 1, 2014, through December 31, 2014. Beneficiaries with
      other parkinsonian syndromes were excluded. Demographic, geographic, prescription
      claims, and other data were extracted from the 2014 Carrier, Beneficiary Summary,
      and Prescription Drug Event research identifiable files of the Centers for
      Medicare & Medicaid Services. Data analysis was conducted from August 1, 2017, to
      November 30, 2017. Main Outcomes and Measures: Primary outcomes were use of
      dementia drug, specific dementia medication, and concurrent exposure to a high
      potency anticholinergic drug and an ACHEI. Descriptive analyses and multivariable
      logistic regression models determined the extent to which patient characteristics
      and comorbid conditions were associated with dementia treatment or with a high
      potency anticholinergic and ACHEI never event. Results: Of 268 407 Medicare
      beneficiaries with Parkinson disease (mean [SD] age, 78.9 [7.5]; 134 575 male
      [50.1%]), most were identified in the files as white (232 831 [86.7%]), followed
      by black (14 629 [5.5%]), Hispanic (7176 [2.7%]), Asian (7115 [2.7%]), and Native
      American (874 [0.3%]). Among these beneficiaries, 73 093 (27.2%) were given a
      prescription for at least 1 antidementia medication. The most commonly prescribed
      medication was donepezil hydrochloride (46 027 [63.0%] users), followed by
      memantine hydrochloride (30 578 [41.8%] users) and rivastigmine tartrate (19 278
      [26.4%] users). Dementia drugs were more likely to be prescribed to black
      (adjusted odds ratio [AOR], 1.33; 95% CI, 1.28-1.38) and Hispanic (AOR, 1.28; 95%
      CI, 1.22-1.35) beneficiaries and less likely for Native American beneficiaries
      (AOR, 0.62; 95% CI, 0.51-0.74). Women were less likely than men to be given a
      prescription for dementia medication (AOR, 0.85; 95% CI, 0.84-0.87). Of the 64
      017 beneficiaries receiving an ACHEI, 28 495 (44.5%) experienced at least 1 high
      potency anticholinergic-ACHEI event. Hispanic (AOR, 1.11; 95% CI, 1.00-1.23) and
      women (AOR, 1.30; 95% CI, 1.25-1.35) beneficiaries had greater odds of
      experiencing this never event. Statistically significant clusters of the
      prevalence of this prescribing error were observed across the United States
      (Moran I = 0.24; P < .001), with clusters of high prevalence in the southern and
      midwestern states. Conclusions and Relevance: Dementia medication use by persons
      with Parkinson disease varies by race/ethnicity and sex; potentially
      inappropriate prescribing is common among those being treated for cognitive
      impairment and varies by race/ethnicity, sex, and geography. These findings may
      serve as national and local targets for improving care quality and outcomes for
      persons with Parkinson disease.

PMID- 30285048
TI  - Fecal Immunochemical Test Screening for Colon and Rectal Cancer.

PMID- 30285049
TI  - Persistence and Drivers of High-Cost Status Among Dual-Eligible Medicare and
      Medicaid Beneficiaries: An Observational Study.
AB  - Background: Little is known about the persistence of high-cost status among dual
      eligible Medicare and Medicaid beneficiaries, who account for a substantial
      proportion of expenditures in both programs. Objective: To determine what
      proportion of this population has persistently high costs. Design: Observational
      study. Setting: Medicare-Medicaid Linked Enrollee Analytic Data Source data for
      2008 to 2010. Participants: 1 928 340 dual-eligible Medicare and Medicaid
      beneficiaries who were alive all 3 years. Measurements: Medicare and Medicaid
      payments for these beneficiaries were calculated for each year. Beneficiaries
      were categorized as high-cost for a given year if their spending was in the top
      10% for that year. Differences in spending were then examined for those who were
      persistently high-cost (all 3 years) versus those who were transiently high-cost
      (2008 but not 2009 or 2010) and those who were non-high-cost in all 3 years.
      Results: In the first year, 192 835 patients were high-cost. More than half
      (54.8%) remained high-cost across all 3 years. These patients were younger than
      transiently high-cost patients, with fewer medical comorbidities and greater
      intellectual impairment. Persistently high-cost patients spent $161 224 per year
      compared with $86 333 per year for transiently high-cost patients and $22 352 per
      year for non-high-cost patients. Most of the spending among persistently high
      cost patients (68.8%) was related to long-term care, and very little (<1%) was
      related to potentially preventable hospitalizations for ambulatory care-sensitive
      conditions. Limitation: Potential misclassification of preventable spending and
      lack of detailed clinical data in administrative claims. Conclusion: A
      substantial majority of high-cost dual-eligible beneficiaries had persistently
      high costs over 3 years, with most of the cost related to long-term care and very
      little related to potentially preventable hospitalizations. Primary Funding
      Source: Peterson Center on Healthcare.

PMID- 30285050
TI  - Association Between Antibiotic Prescribing for Respiratory Tract Infections and
      Patient Satisfaction in Direct-to-Consumer Telemedicine.

PMID- 30285051
TI  - Drinking More Water for Prevention of Recurrent Cystitis.

PMID- 30285052
TI  - Caution Advised for Readers of Comments Related to Retracted Article.

PMID- 30285053
TI  - Fibromuscular Dysplasia and Its Neurologic Manifestations: A Systematic Review.
AB  - Importance: Data on neurologic manifestations of fibromuscular dysplasia (FMD)
      are rare, and current knowledge remains limited. Objectives: To present a
      comprehensive review of the epidemiologic characteristics, management, and
      prognosis of the neurologic manifestations associated with cerebrovascular FMD
      (ie, involving cervical or intracranial arteries) and to guide future research
      priorities. Evidence Review: References were identified through searches of
      PubMed from inception to December 2017 using both the medical subject headings
      and text words. Additional sources were also identified by reviewing reference
      lists of relevant articles and through searches of the authors' personal files.
      Selected articles described at least 1 clinical or radiologic feature and/or
      outcome of cerebrovascular FMD. Isolated case reports could be included if they
      described interesting or noteworthy manifestations of FMD. Findings: A total of
      84 relevant references were identified. Diagnosis of cerebrovascular FMD is based
      on the appearance of alternating arterial dilatation and constriction ("string of
      beads") or of focal narrowing, with no sign of atherosclerotic or inflammatory
      lesions. Although the diagnosis is easily apparent on results of radiographic
      imaging, making a diagnosis can be challenging in children or individuals with
      atypical phenotypes, such as purely intracranial FMD and arterial diaphragm.
      Involvement of multiple arteries is common, and there is increased incidence of
      cervical artery dissection and intracranial aneurysms. A variant in the PHACTR1
      gene has been associated with FMD as well as cervical artery dissection and
      migraine, although less than 5% of cases of FMD are familial. Headaches, mainly
      of the migraine type, are observed in up to 70% of patients with FMD.
      Cerebrovascular FMD is mostly asymptomatic, but the most frequent neurologic
      manifestations include transient ischemic attack and ischemic stroke, notably in
      the presence of associated cervical artery dissection. Other conditions
      associated with FMD include subarachnoid hemorrhage and, rarely, intracranial
      hemorrhage. Management relies on observational data and expert opinion.
      Antiplatelet therapy is considered reasonable to prevent thromboembolic
      complications. Endovascular therapy is typically restricted to cases with
      symptomatic stenosis despite optimal medical therapy or in those with rupture of
      an intracranial aneurysm. Conclusions and Relevance: Longitudinal cohort studies
      of individuals of multiple ethnicities with biosampling are needed to better
      understand the risk factors, pathophysiological features, and outcomes of FMD.
      Patient advocacy groups could assist researchers in answering patient-centered
      questions regarding FMD.

PMID- 30285054
TI  - Efficacy of Low-Dose Amitriptyline for Chronic Low Back Pain: A Randomized
      Clinical Trial.
AB  - Importance: Antidepressants at low dose are commonly prescribed for the
      management of chronic low back pain and their use is recommended in international
      clinical guidelines. However, there is no evidence for their efficacy. Objective:
      To examine the efficacy of a low-dose antidepressant compared with an active
      comparator in reducing pain, disability, and work absence and hindrance in
      individuals with chronic low back pain. Design, Setting, and Participants: A
      double-blind, randomized clinical trial with a 6-month follow-up of adults with
      chronic, nonspecific, low back pain who were recruited through hospital/medical
      clinics and advertising was carried out. Intervention: Low-dose amitriptyline (25
      mg/d) or an active comparator (benztropine mesylate, 1 mg/d) for 6 months. Main
      Outcomes and Measures: The primary outcome was pain intensity measured at 3 and 6
      months using the visual analog scale and Descriptor Differential Scale. Secondary
      outcomes included disability assessed using the Roland Morris Disability
      Questionnaire and work absence and hindrance assessed using the Short Form Health
      and Labour Questionnaire. Results: Of the 146 randomized participants (90 [61.6%]
      male; mean [SD] age, 54.8 [13.7] years), 118 (81%) completed 6-month follow-up.
      Treatment with low-dose amitriptyline did not result in greater pain reduction
      than the comparator at 6 (adjusted difference, -7.81; 95% CI, -15.7 to 0.10) or 3
      months (adjusted difference, -1.05; 95% CI, -7.87 to 5.78), independent of
      baseline pain. There was no statistically significant difference in disability
      between the groups at 6 months (adjusted difference, -0.98; 95% CI, -2.42 to
      0.46); however, there was a statistically significant improvement in disability
      for the low-dose amitriptyline group at 3 months (adjusted difference, -1.62; 95%
      CI, -2.88 to -0.36). There were no differences between the groups in work
      outcomes at 6 months (adjusted difference, absence: 1.51; 95% CI, 0.43-5.38;
      hindrance: 0.53; 95% CI, 0.19-1.51), or 3 months (adjusted difference, absence:
      0.86; 95% CI, 0.32-2.31; hindrance: 0.78; 95% CI, 0.29-2.08), or in the number of
      participants who withdrew owing to adverse events (9 [12%] in each group; chi2 =
      0.004; P = .95). Conclusions and Relevance: This trial suggests that
      amitriptyline may be an effective treatment for chronic low back pain. There were
      no significant improvements in outcomes at 6 months, but there was a reduction in
      disability at 3 months, an improvement in pain intensity that was nonsignificant
      at 6 months, and minimal adverse events reported with a low-dose, modest sample
      size and active comparator. Although large-scale clinical trials that include
      dose escalation are needed, it may be worth considering low-dose amitriptyline if
      the only alternative is an opioid. Trial Registration: anzctr.org.au Identifier:
      ACTRN12612000131853.

PMID- 30285055
TI  - Divergent Long-Term Detection Rates of Proximal and Distal Advanced Neoplasia in
      Fecal Immunochemical Test Screening Programs: A Retrospective Cohort Study.
AB  - Background: Short-term studies have reported that the fecal immunochemical test
      (FIT) is less accurate in detecting proximal than distal colorectal neoplasia.
      Objective: To assess the long-term detection rates for advanced adenoma and
      colorectal cancer (CRC), according to anatomical location. Design: Retrospective
      study. Setting: Population-based, organized screening program in the Veneto
      region of Italy. Participants: Persons aged 50 to 69 years who completed 6 rounds
      of FIT screening. Measurements: At each screening round, the detection rates for
      advanced adenoma and cancer, as well as the proportional interval cancer rate
      (PICR), were calculated by anatomical location (proximal colon, distal colon, or
      rectum). Results: Between 2002 and 2014, a total of 123 347 participants had 441
      647 FITs. The numbers of advanced adenomas and cancer cases detected,
      respectively, were 1704 and 200 in the proximal colon, 3703 and 324 in the distal
      colon, and 1220 and 209 in the rectum. Although the detection rate for proximal
      colon cancer declined only from the first to the second screening round (0.63 to
      0.36 per 1000 screenees), the rate for both distal colon and rectal cancer
      steadily decreased across 6 rounds (distal colon, 1.65 in the first round to 0.17
      in the sixth; rectum, 0.82 in the first round to 0.17 in the sixth). Similar
      trends were found for advanced adenoma (proximal colon, 5.32 in the first round
      to 4.22 in the sixth; distal colon, 15.2 in the first round to 5.02 in the
      sixth). Overall, 150 cases of interval cancer were diagnosed. The PICR was higher
      in the proximal colon (25.2% [95% CI, 19.9% to 31.5%]) than the distal colon
      (6.0% [CI, 3.9% to 8.9%]) or rectum (9.9% [CI, 6.9% to 13.7%]). Limitations:
      Participants with irregular attendance were censored. Those who had a false
      positive result on a previous FIT but negative colonoscopy results were included
      in subsequent rounds. Conclusion: This FIT-based, multiple-round, long-term
      screening program had a negligible reduction in detection rates for neoplastic
      lesions in the proximal versus the distal colon after the first round. This was
      related to a higher PICR in the proximal colon and suboptimal efficacy in
      preventing the age-related proximal shifting of CRC. Primary Funding Source:
      None.

PMID- 30285056
TI  - Association of Age at Onset and Longitudinal Course of Prefrontal Function in
      Youth With Schizophrenia.
AB  - Importance: The extent of cognitive deterioration after schizophrenia (SZ) onset
      is poorly understood because prior longitudinal studies used small samples of
      older individuals with established illness. Objective: To examine the association
      of age at onset and subsequent longitudinal course of prefrontal activity during
      the first 2 years of illness in youths with SZ and healthy control participants
      (HCs). Design, Setting, and Participants: This naturalistic, longitudinal,
      functional magnetic resonance imaging (fMRI) study included patients with recent
      onset SZ and HCs aged 12 to 25 years enrolled in an ongoing study of cognition in
      recent-onset psychosis in the Sacramento, California, area from October 13, 2004,
      through June 25, 2013. Participants completed clinical assessments and an
      established measure of cognitive control, the AX Continuous Performance Task (AX
      CPT), during fMRI at baseline and at 6-, 12-, and 24-month follow-up. Whole
      brain, voxelwise, and an a priori dorsolateral prefrontal cortex (DLPFC) region
      of interest analyses were performed. Group differences in developmental
      trajectories were examined by focusing on behavioral performance (d'-context) and
      cognitive control-associated brain activity. The association of antipsychotic
      medication and clinical factors were also examined. Data were analyzed from April
      15, 2015, through August 29, 2017. Main Outcomes and Measures: Primary outcomes
      included group differences (HC vs SZ) in behavioral performance (d'-context from
      AX-CPT) and brain activity for cue B-A trials of the AX-CPT in an a priori DLPFC
      region of interest at baseline and across the age span. Secondary analysis
      examined the influence of antipsychotics on behavioral performance and DLPFC
      activity. Results: Among the sample of 180 participants (66.1% male; mean [SD]
      age at baseline, 19.2 [3.2] years), 87 patients with SZ (mean [SD] age, 19.6
      [3.0] years) showed impaired performance compared with 93 HCs (mean [SD] age,
      18.8 [3.4] years) across the age span (estimated difference [SE], -0.571 [0.12],
      d'-context; P < .001). Patients with SZ showed reduced activation in the DLPFC
      and parietal cortex (false discovery rate cluster corrected to P < .05) compared
      with HCs under conditions of high cognitive control at baseline. Region-of
      interest analysis showed reduced activation in the DLPFC bilaterally for patients
      with SZ, with a trajectory that paralleled that of HCs across the age span (left
      DLPFC beta [SE] estimates, 0.409 [0.165] for the HC group and -0.285 [0.130] for
      the SZ group [main effect of group, P = .03]; right DLPFC beta [SE] estimates,
      0.350 [0.103] for the HC group and -0.469 [0.157] for the SZ group [P = .003]).
      Antipsychotic medication, clinical symptoms, and global functioning were
      associated with SZ performance. Conclusions and Relevance: During the initial 1
      to 2 years after illness onset, young individuals with SZ showed deficits in
      DLPFC activation and cognitive control, with developmental trajectories
      comparable to those of HCs. Younger age at onset was not associated with reduced
      cognition or activation. For individuals contributing to longitudinal analysis,
      results suggest that young patients do not show deterioration or disruption of
      ongoing brain development in the initial years after illness onset.

PMID- 30285057
TI  - Association of Initially Normal Coronary Arteries With Normal Findings on Follow
      up Echocardiography in Patients With Kawasaki Disease.
AB  - Importance: American Heart Association guidelines recommend echocardiography in
      Kawasaki disease at baseline, 1 to 2 weeks, and 4 to 6 weeks after treatment to
      detect coronary artery abnormalities. However, these examinations are expensive
      and may require sedation in young children, which is burdensome and carries some
      risk. Objective: To assess the benefit of additional echocardiographic imaging at
      6 weeks in patients with uncomplicated Kawasaki disease who had previously normal
      coronary arteries. Design, Setting, and Participants: This is a retrospective
      review of patients with Kawasaki disease who were cared for between 1995 and 2014
      in 2 academic pediatric referral practices Eligibility criteria included
      receiving intravenous immunoglobulin treatment for acute Kawasaki disease at a
      center; the absence of significant congenital heart disease; available
      echocardiographic measurements of both the right and left anterior descending
      coronary arteries at 10 days or less after diagnosis (baseline), 2 (+/-1) weeks,
      and 6 (+/-3) weeks of illness; and normal coronary arteries at baseline and 2
      weeks, defined as maximum coronary artery z scores less than 2.0 and no distal
      aneurysms. Data analysis was completed from March 2015 to November 2015. Main
      Outcomes and Measures: The number of patients with right coronary artery or left
      anterior descending coronary artery z scores of 2.0 or more at 6 weeks. Results:
      The median age of the 464 included patients was 3.3 years (interquartile range,
      1.8-5.4 years); 264 (56.9%) were male, 351 of 414 for whom data were available
      (84.8%) had complete Kawasaki disease, and 66 (14.2%) received additional
      intravenous immunoglobulin treatment. At 6 weeks of illness, 456 patients (98.3%)
      who had had normal coronary artery z scores at baseline and 2 weeks continued to
      have normal z scores. Of the remaining 8 patients (1.7%), the maximum z score
      within 6 weeks was 2.0 to 2.4 in 5 patients (1.2%), 2.5 to 2.9 in 1 patient
      (0.2%), and 3.0 or more in 2 patients (0.4% [95% CI, 0.1%-1.5%]). Coronary artery
      dimensions ultimately normalized in all but 1 patient, who had minimal dilation
      at 6 weeks (right coronary artery z score, 2.1). Sensitivity analyses using less
      restrictive cut points (eg, a maximum z score <2.5) or less restrictive timing
      windows (eg, considering patients with incomplete echocardiographic data within
      21 days) gave similar results; in these analyses, 454 to 463 of 464 patients (98%
      to 99.7%) had coronary artery z scores of less than 2.5 at 6 weeks. Conclusions
      and Relevance: New abnormalities in coronary arteries are rarely detected at 6
      weeks in patients with Kawasaki disease who have normal measurements at baseline
      and 2 weeks of illness, suggesting that the 6-week echocardiographic imaging may
      be unnecessary in patients with uncomplicated Kawasaki disease and z scores less
      than 2.0 in the first 2 weeks of illness.

PMID- 30285059
TI  - The New American Joint Committee on Cancer TNM Staging System for Pancreatic
      Cancer-Balancing Usefulness With Prognostication.

PMID- 30285060
TI  - Alopecia Universalis and Chronic Graft-vs-Host Disease Treated With Ruxolitinib.

PMID- 30285058
TI  - Outcomes of Patients With Asymptomatic Aortic Stenosis Followed Up in Heart Valve
      Clinics.
AB  - Importance: The natural history and the management of patients with asymptomatic
      aortic stenosis (AS) have not been fully examined in the current era. Objective:
      To determine the clinical outcomes of patients with asymptomatic AS using data
      from the Heart Valve Clinic International Database. Design, Setting, and
      Participants: This registry was assembled by merging data from prospectively
      gathered institutional databases from 10 heart valve clinics in Europe, Canada,
      and the United States. Asymptomatic patients with an aortic valve area of 1.5 cm2
      or less and preserved left ventricular ejection fraction (LVEF) greater than 50%
      at entry were considered for the present analysis. Data were collected from
      January 2001 to December 2014, and data were analyzed from January 2017 to July
      2018. Main Outcomes and Measures: Natural history, need for aortic valve
      replacement (AVR), and survival of asymptomatic patients with moderate or severe
      AS at entry followed up in a heart valve clinic. Indications for AVR were based
      on current guideline recommendations. Results: Of the 1375 patients included in
      this analysis, 834 (60.7%) were male, and the mean (SD) age was 71 (13) years. A
      total of 861 patients (62.6%) had severe AS (aortic valve area less than 1.0
      cm2). The mean (SD) overall survival during medical management (mean [SD] follow
      up, 27 [24] months) was 93% (1%), 86% (2%), and 75% (4%) at 2, 4, and 8 years,
      respectively. A total of 104 patients (7.6%) died under observation, including 57
      patients (54.8%) from cardiovascular causes. The crude rate of sudden death was
      0.65% over the duration of the study. A total of 542 patients (39.4%) underwent
      AVR, including 388 patients (71.6%) with severe AS at study entry and 154 (28.4%)
      with moderate AS at entry who progressed to severe AS. Those with severe AS at
      entry who underwent AVR did so at a mean (SD) of 14.4 (16.6) months and a median
      of 8.7 months. The mean (SD) 2-year and 4-year AVR-free survival rates for
      asymptomatic patients with severe AS at baseline were 54% (2%) and 32% (3%),
      respectively. In those undergoing AVR, the 30-day postprocedural mortality was
      0.9%. In patients with severe AS at entry, peak aortic jet velocity (greater than
      5 m/s) and LVEF (less than 60%) were associated with all-cause and cardiovascular
      mortality without AVR; these factors were also associated with postprocedural
      mortality in those patients with severe AS at baseline who underwent AVR
      (surgical AVR in 310 patients; transcatheter AVR in 78 patients). Conclusions and
      Relevance: In patients with asymptomatic AS followed up in heart valve centers,
      the risk of sudden death is low, and rates of overall survival are similar to
      those reported from previous series. Patients with severe AS at baseline and peak
      aortic jet velocity of 5.0 m/s or greater or LVEF less than 60% have increased
      risks of all-cause and cardiovascular mortality even after AVR. The potential
      benefit of early intervention should be considered in these high-risk patients.

PMID- 30285061
TI  - Association Between the Experimental Kickoff Rule and Concussion Rates in Ivy
      League Football.

PMID- 30285062
TI  - Systolic and Diastolic Blood Pressure Variability as Risk Factors for Adverse
      Events After Coronary Artery Bypass Grafting.

PMID- 30285064
TI  - Acrodermatitis Continua of Hallopeau.

PMID- 30285063
TI  - Postoperative Outcomes of Screen-Detected vs Non-Screen-Detected Colorectal
      Cancer in the Netherlands.
AB  - Importance: The nationwide fecal immunochemical test-based screening program has
      influenced surgical care for patients with colorectal cancer (CRC) in the
      Netherlands, although these implications have not been studied in much detail so
      far. Objective: To compare surgical outcomes of patients diagnosed as having CRC
      through the fecal immunochemical test-based screening program (screen detected)
      and patients with non-screen-detected CRC. Design, Setting, and Participants:
      This was a population-based comparative cohort study using the Dutch ColoRectal
      Audit and analyzed all Dutch hospitals performing CRC resections. Patients who
      underwent elective resection for CRC between January 2011 to December 2016 were
      included. Interventions: Colorectal cancer surgery. Main Outcomes and Measures:
      Postoperative nonsurgical complications, postoperative surgical complications,
      postoperative 30-day or in-hospital mortality, and complicated course
      (postoperative complication resulting in a hospital stay >14 days and/or a
      reintervention and/or mortality). A risk-stratified comparison was made for
      different postoperative outcomes based on screening status (screen detected vs
      not screen detected), cancer stage (I-IV), and for cancer stage I to III also on
      age (aged <=70 years and >70 years) and American Society of Anesthesiologists
      score (I-II and III-IV). To determine any residual case-mix-corrected differences
      in outcomes between patients with screen-detected and non-screen-detected cancer,
      univariable and multivariable logistic regression analyses were performed.
      Results: In total, 36 242 patients with colon cancer and 17 416 patients with
      rectal cancer were included for analysis. Compared with patients with non-screen
      detected CRC, screen-detected patients were younger (mean [SD] age, 68 [5] vs 70
      [11] years), more often men (3777 [60%] vs 13 506 [57%]), and had lower American
      Society of Anesthesiologists score (American Society of Anesthesiologists score
      III+: 838 [13%] vs 5529 [23%]). Patients with stage I to III colon cancer who
      were screen detected had a significantly lower mortality and complicated course
      rate compared with non-screen-detected patients. For patients with rectal cancer,
      only a significant difference was found in mortality rate in patients with a
      cancer stage IV disease, which was higher in the screen-detected group. Compared
      with non-screen-detected colon cancer, an independent association was found for
      screen-detected colon cancer on nonsurgical complications (adjusted odds ratio,
      0.81; 95% CI, 0.73-0.91), surgical complications (adjusted odds ratio, 0.80; 95%
      CI, 0.72-0.89), and complicated course (adjusted odds ratio, 0.80; 95% CI, 0.71
      0.90). Screen-detected rectal cancer had significantly higher odds on mortality.
      Conclusions and Relevance: Postoperative outcomes were significantly better for
      patients with colon cancer referred through the fecal immunochemical test-based
      screening program compared with non-screen-detected patients. These differences
      were not found in patients with rectal cancer. The outcomes of patients with
      screen-detected colon cancer were still better after an extensive case-mix
      correction, implying additional underlying factors favoring patients referred for
      surgery through the screening program.

PMID- 30285065
TI  - Companies Tout Psychiatric Pharmacogenomic Testing, But Is It Ready for a Store
      Near You?

PMID- 30285066
TI  - Establishing Pediatric and Adult RBC Reference Intervals With NHANES Data Using
      Piecewise Regression.
AB  - Objectives: To develop age- and sex-specific RBC reference intervals using the
      National Health and Nutrition Examination Survey (NHANES) 1999 to 2012, a large
      nationally representative, population-based, cross-sectional database (n =
      44,328). Methods: Comprehensive medical data were used to define a "healthy"
      population. Reference intervals for RBC count, hemoglobin, hematocrit, mean cell
      hemoglobin, mean cell hemoglobin concentration, mean cell volume, and red cell
      distribution width were computed using piecewise regression, an evidence-based
      statistical procedure that identifies breakpoints. Results: The derived reference
      intervals were sex specific, unlike many current standards, and more precise for
      individuals of different ages, especially for children, adolescents, and elderly
      individuals, as additional breakpoints were detected for these groups. Suggested
      reference values for hematocrit and hemoglobin of older adult males were
      substantially lower than current values. Conclusions: The reference intervals
      provided here, based on a large, nationally representative healthy population,
      contribute to the ongoing transition to precision medicine.

PMID- 30285067
TI  - HLA-Mediated Platelet Refractoriness: An ACLPS Critical Review.
AB  - Objectives: To provide an overview of the complexities associated with the human
      leukocyte antigen (HLA)-mediated platelet refractoriness. HLA antibody detection
      technologies and limitations associated with methodologies are discussed.
      Methods: A case scenario and review of relevant literature describing platelet
      refractoriness are presented, followed by a discussion of HLA antibody testing.
      Results: Following diagnosis of HLA-mediated refractoriness, a decision is made
      regarding the approach to obtain the appropriate platelets. The panel reactive
      antibodies (PRA) % of the patient, HLA typing, and limitations of the HLA testing
      should be taken into account when deciding which type of product would be the
      best option for a given patient. Conclusions: Following confirmation and review
      of HLA antibody testing, platelets are ordered based upon the PRA% and approach
      employed, HLA-matched platelets, antigen restricted platelets, or cross-matched
      platelets. The platelets are transfused and a posttransfusion increment count is
      monitored to determine transfusion success.

PMID- 30285068
TI  - Unexpectedly High Prevalence of Cystoisospora belli Infection in Acalculous
      Gallbladders of Immunocompetent Patients.
AB  - Objectives: Indications for cholecystectomy have changed dramatically over the
      past three decades. Cystoisospora belli has been reported in cholecystectomy
      specimens of immunocompetent patients. The present study was designed to
      determine the prevalence and clinical association of C belli in the gallbladder.
      Methods: The study included retrospective review of cholecystectomy specimens (n
      = 401) removed for various indications, and a prospective cohort of
      cholecystectomy specimens (n = 22) entirely submitted for histologic evaluation.
      Correlations of presence of C belli with age, sex, clinical indication, and
      abnormalities of preoperative laboratory values were assessed by Fisher exact
      test. Results: C belli was identified in 39/401 (9.7%) of the retrospective
      cohort, and 6/22 (27.3%) of the entirely submitted specimens. The presence of C
      belli showed no correlation with age, sex, clinical indication, or laboratory
      abnormalities. Conclusions: C belli resides in a latent state in the gallbladder
      and may be best considered a commensal organism.

PMID- 30285069
TI  - Efficacy and Safety of Antibiotic Therapy in Early Cutaneous Lyme Borreliosis: A
      Network Meta-analysis.
AB  - Importance: Controversies about the choice of antibiotic agent and treatment
      modality exist in the management of erythema migrans in early cutaneous Lyme
      borreliosis (LB). Objective: To conduct a network meta-analysis (NMA) of all
      randomized clinical trials on various antibiotic agents and treatment modalities
      in early cutaneous LB. Data Sources: Electronic searches in MEDLINE, Embase, and
      the Cochrane Central Register of Controlled Trials were conducted from inception
      until July 2017. The reference lists of the included studies were hand searched,
      authors were contacted, and ongoing trials were searched at ClinicalTrials.gov.
      Study Selection: One reviewer screened the titles and abstracts of the 9975
      reports identified by the electronic searches. Full-text copies of 161
      potentially relevant articles were obtained, and 2 reviewers independently
      assessed those articles for inclusion. Adults with a physician-confirmed early
      localized skin infection who were treated with antibiotics of any dose or
      duration were included. Data Extraction and Synthesis: Two reviewers
      independently extracted data on study, patient, and intervention characteristics.
      Network meta-analyses on treatment effects and adverse outcomes were calculated
      with a frequentist approach using the R package netmeta. The Grading of
      Recommendations Assessment, Development and Evaluation guidance for NMA was used
      to assess the certainty of evidence. Main Outcomes and Measures: Treatment
      effects for response to treatment (resolution of symptoms) and treatment-related
      adverse events. Results: Overall, 19 studies (2532 patients) were included. The
      mean patient age ranged between 37 and 56 years, and the percentage of female
      patients ranged from 36% to 60%. The antibiotics investigated were doxycycline,
      cefuroxime axetil, ceftriaxone, amoxicillin, azithromycin, penicillin V, and
      minocycline. Pooled effect sizes from NMAs did not suggest any significant
      differences in treatment response by antibiotic agent (eg, amoxicillin vs
      doxycycline odds ratio, 1.26; 95% CI, 0.41-3.87), dose, or duration (eg,
      doxycycline, 200 mg/d for 3 weeks, vs doxycycline, 200 mg/d for 2 weeks, odds
      ratio, 1.28; 95% CI, 0.49-3.34). Treatment failures were rare at both 2 months
      (4%; 95% CI, 2%-5%) and 12 months (2%, 95% CI, 1%-3%) after treatment initiation.
      There were also no differences in the effect sizes among antibiotic agents and
      treatment modalities for treatment-related adverse outcomes, which were generally
      mild to moderate. Certainty of evidence was categorized as low and very low
      mostly because of imprecision, indirectness, and study limitations (high risk of
      bias) of the included studies. Conclusions and Relevance: This NMA suggests that
      neither the antibiotic agent nor treatment modality contributed to comparative
      effectiveness or drug-related adverse outcomes. This finding is relevant for
      physicians treating patients with LB and for patient decision making.

PMID- 30285070
TI  - Prevalence of Sexual Harassment in Academic Medicine.

PMID- 30285071
TI  - Association of Sexual Harassment and Sexual Assault With Midlife Women's Mental
      and Physical Health.
AB  - Importance: Sexual harassment and sexual assault are prevalent experiences among
      women. However, their association with health indices is less well understood.
      Objective: To investigate the association of history of sexual harassment and
      sexual assault with blood pressure, mood, anxiety, and sleep among midlife women.
      Design, Setting, and Participants: Nonsmoking women without cardiovascular
      disease were recruited from the community to undergo physical measurements (blood
      pressure, height, weight), medical history, and questionnaire psychosocial
      assessments (workplace sexual harassment, sexual assault, depression, anxiety,
      sleep). Exposures: Sexual harassment and sexual assault. Main Outcomes and
      Measures: Blood pressure, depressive symptoms, anxiety, and sleep
      characteristics. Results: Among the 304 nonsmoking women aged 40 to 60 years who
      participated in the study, all were free of clinical cardiovascular disease, and
      the mean (SD) age was 54.05 (3.99) years. A total of 19% reported a history of
      workplace sexual harassment (n = 58), and 22% reported a history of sexual
      assault (n = 67). Sexual harassment was related to significantly greater odds of
      stage 1 or 2 hypertension among women not taking antihypertensives (odds ratio
      [OR], 2.36; 95% CI, 1.10-5.06; P = .03) as well as clinically poor sleep (OR,
      1.89; 95% CI, 1.05-3.42; P = .03), after adjusting for covariates. Sexual assault
      was associated with significantly greater odds of clinically elevated depressive
      symptoms (OR, 2.86; 95% CI, 1.42-5.77; multivariable P = .003), clinically
      relevant anxiety (OR, 2.26; 95% CI, 1.26-4.06; P = .006), and clinically poor
      sleep (OR, 2.15; 95% CI, 1.23-3.77; multivariable P = .007), after adjusting for
      covariates. Conclusions and Relevance: Sexual harassment and sexual assault are
      prevalent experiences among midlife women. Sexual harassment was associated with
      higher blood pressure and poorer sleep. Sexual assault was associated with poorer
      mental health and sleep. Efforts to improve women's health should target sexual
      harassment and assault prevention.

PMID- 30285072
TI  - Reconciling the Discrepancies in Medicine's Relationship to Medical Marijuana.

PMID- 30285073
TI  - The "Public Charge" Proposal and Public Health: Implications for Patients and
      Clinicians.

PMID- 30285074
TI  - Between-Race Differences in Processes Predicting Physician Communication for
      African American and European American Recipients of Breast Density
      Notifications.
AB  - Background: Breast density notification laws mandate reporting of dense breast to
      applicable women. The same psychological and systemic barriers that yield between
      race differences in mammography use will probably yield between-race differences
      in women's psychological and behavioral responses to breast density
      notifications. Purpose: We used the theory of planned behavior as a framework to
      examine between-race differences in the likelihood of following-up with
      physicians after receiving breast density notifications and to examine
      differences in African American and Caucasian American women's behavioral
      decision-making processes. Methods: A subset of 212 African American and
      Caucasian American women who participated in an initial and follow-up survey
      examining responses to breast density notifications were examined for this study.
      Participants reported background and demographic measures, psychological
      responses to receiving notifications, and planned behavior measures related to
      following up with physicians approximately 2 weeks after receiving their
      mammogram reports. Participants self-reported their behaviors 3 months later.
      Results: There were no between-race differences in self-reported physician
      communication; however, there were differences in processes that predicted
      behavior. For Caucasian American women, behavioral intentions, education, and
      income predicted behaviors. Instead of intentions, group-based medical suspicion,
      confusion, breast cancer worry, and breast density anxiety predicted behaviors
      for African American women. Conclusions: Behavioral decision-making processes for
      Caucasian American women were in line with well-validated theoretical
      predictions. For African American women, race-related medical suspicion, prior
      breast density awareness, and emotional responses to breast density notifications
      predicted behavior. The results highlight the need to focus on racially distinct
      psychological targets when designing interventions to support guideline
      concordant behavioral decisions among women who receive breast density
      notifications.

PMID- 30285075
TI  - Eliminating Poverty in the 21st Century: The Role of Health and Human Capital.

PMID- 30285077
TI  - Framework for Faculty Development in Resident Autonomy and Entrustment in the
      Operating Room.

PMID- 30285076
TI  - International Validation of the Eighth Edition of the American Joint Committee on
      Cancer (AJCC) TNM Staging System in Patients With Resected Pancreatic Cancer.
AB  - Importance: The recently released eighth edition of the American Joint Committee
      on Cancer TNM staging system for pancreatic cancer seeks to improve prognostic
      accuracy but lacks international validation. Objective: To validate the eighth
      edition of the American Joint Committee on Cancer TNM staging system in an
      international cohort of patients with resected pancreatic ductal adenocarcinoma.
      Design, Setting, and Participants: This international multicenter cohort study
      took place in 5 tertiary centers in Europe and the United States from 2000 to
      2015. Patients who underwent pancreatoduodenectomy for nonmetastatic pancreatic
      ductal adenocarcinoma were eligible. Data analysis took place from December 2017
      to April 2018. Exposures: Patients were retrospectively staged according to the
      seventh and eighth editions of the TNM staging system. Main Outcomes and
      Measures: Prognostic accuracy on survival rates, assessed by Kaplan-Meier and
      multivariate Cox proportional hazards analyses and concordance statistics.
      Results: A total of 1525 consecutive patients were included (median [IQR] age, 66
      (58-72) years; 802 (52.6%) male). Distribution among stages via the seventh
      edition was stage IA in 41 patients (2.7%), stage IB in 42 (2.8%), stage IIA in
      200 (13.1%), stage IIB in 1229 (80.6%), and stage III in 12 (0.8%); this changed
      with use of the eighth edition to stage IA in 118 patients (7.7%), stage IB in
      144 (9.4%), stage IIA in 22 (1.4%), stage IIB in 643 (42.2%), and stage III in
      598 (39.2%). With the eighth edition, 774 patients (50.8%) migrated to a
      different stage; 183 (12.0%) were reclassified to a lower stage and 591 (38.8%)
      to a higher stage. Median overall survival for the entire cohort was 24.4 months
      (95% CI, 23.4-26.2 months). On Kaplan-Meier analysis, 5-year survival rates
      changed from 38.2% for patients in stage IA, 34.7% in IB, 35.3% in IIA, 16.5% in
      IIB, and 0% in stage III (log-rank P < .001) via classification with the seventh
      edition to 39.2% for patients in stage IA, 33.9% in IB, 27.6% in IIA, 21.0% in
      IIB, and 10.8% in stage III (log-rank P < .001) with the eighth edition. For
      patients who were node negative, the T stage was not associated with
      prognostication of survival in either edition. In the eighth edition, the N stage
      was associated with 5-year survival rates of 35.6% in N0, 20.8% in N1, and 10.9%
      in N2 (log-rank P < .001). The C statistic improved from 0.55 (95% CI, 0.53-0.57)
      for the seventh edition to 0.57 (95% CI, 0.55-0.60) for the eighth edition.
      Conclusions and Relevance: The eighth edition of the TNM staging system
      demonstrated a more equal distribution among stages and a modestly increased
      prognostic accuracy in patients with resected pancreatic ductal adenocarcinoma
      compared with the seventh edition. The revised T stage remains poorly associated
      with survival, whereas the revised N stage is highly prognostic.

PMID- 30285078
TI  - Antibiotic Prescribing for Respiratory Tract Infections and Encounter Length: An
      Observational Study of Telemedicine.

PMID- 30285079
TI  - Agreement Between the Spatiotemporal Gait Parameters of Healthy Adults From the
      OptoGait System and a Traditional Three-Dimensional Motion Capture System.
AB  - While previous research has assessed the validity of the OptoGait system to the
      GAITRite walkway and an instrumented treadmill, no research to date has assessed
      this system against a traditional three-dimensional motion analysis system.
      Additionally, previous research has shown that the OptoGait system shows
      systematic bias when compared to other systems due to the configuration of the
      system's hardware. This study examined the agreement between the spatiotemporal
      gait parameters calculated from the OptoGait system and a three-dimensional
      motion capture (14 camera Vicon motion capture system and 2 AMTI force plates) in
      healthy adults. Additionally, a range of filter settings for the OptoGait were
      examined to determine if it was possible to eliminate any systematic bias between
      the OptoGait and the three-dimensional motion analysis system. Agreement between
      the systems was examined using 95% limits of agreement by Bland and Altman and
      the intraclass correlation coefficient. A repeated measure ANOVA was used to
      detect any systematic differences between the systems. Findings confirm the
      validity of the OptoGait system for the evaluation of spatiotemporal gait
      parameters in healthy adults. Furthermore, recommendations on filter settings
      which eliminate the systematic bias between the OptoGait and the three
      dimensional motion analysis system are provided.

PMID- 30285080
TI  - Prescribed Exercise With Compression vs Compression Alone in Treating Patients
      With Venous Leg Ulcers: A Systematic Review and Meta-analysis.
AB  - Importance: Exercise is recommended as an adjuvant treatment for venous leg
      ulceration (VLU) to improve calf muscle pump function. However, the association
      of exercise with VLU healing has not been properly aggregated, and the
      effectiveness of different exercise interventions has not been characterized.
      Objective: To summarize the association of different exercise interventions with
      VLU healing when used as an adjuvant to any form of compression. Data Sources:
      The Cochrane Controlled Trials Register, MEDLINE, Embase, CINAHL, PsycInfo, and
      SCOPUS databases were searched through October 9, 2017. Study Selection:
      Randomized clinical trials (RCTs) of any exercise compared with no exercise in
      participants with VLU were included, where compression was used as standard
      therapy and a healing outcome was reported. Independent title screening and full
      text review by 2 authors (A.J., J.S.) with appeal to a third author (J.P.) if
      disagreement was unresolved. Of the 519 articles screened, a total of 6 (1.2%)
      studies met the inclusion criteria for systematic review, including 5 for meta
      analysis. Data Extraction and Synthesis: Independent quality assessment for
      Cochrane risk of bias and data extraction by 2 authors with appeal to third
      author if disagreement unresolved (PRISMA). Data pooled using fixed effects
      model. Main Outcomes and Measures: The a priori primary outcome was any healing
      outcome (proportion healed, time to healing, or change in ulcer area). Secondary
      outcomes (adverse events, costs, and health-related quality of life) were only
      collected if a primary outcome was reported. Results: Six RCTs were identified
      and 5 (190 participants) met inclusion criteria for meta-analysis. The exercise
      interventions were progressive resistance exercise alone (2 RCTs, 53
      participants) or combined with prescribed physical activity (2 RCTs, 102
      participants), walking only (1 RCT, 35 participants), or ankle exercises (1 RCT,
      40 participants). Overall, exercise was associated with increased VLU healing at
      12 weeks although the effect was imprecise (additional 14 cases healed per 100
      patients; 95% CI, 1-27 cases per 100; P = .04). The combination of progressive
      resistance exercise plus prescribed physical activity appeared to be most
      effective, again with imprecision (additional 27 cases healed per 100 patients;
      95% CI, 9-45 cases per 100; P = .004). Conclusions and Relevance: The evidence
      base may now be sufficiently suggestive for clinicians to consider recommending
      simple progressive resistance and aerobic activity to suitable patients with VLU
      while further research is produced.

PMID- 30285082
TI  - Commentary on: An Analysis of Plastic Surgeons' Social Media Use and Perceptions.

PMID- 30285081
TI  - Evaluating Progression-Free Survival as a Surrogate Outcome for Health-Related
      Quality of Life in Oncology: A Systematic Review and Quantitative Analysis.
AB  - Importance: Progression-free survival (PFS) has become a commonly used outcome to
      assess the efficacy of new cancer drugs. However, it is not clear if delay in
      progression leads to improved quality of life with or without overall survival
      benefit. Objective: To evaluate the association between PFS and health-related
      quality of life (HRQoL) in oncology through a systematic review and quantitative
      analysis of published randomized clinical trials. Eligible trials addressed oral,
      intravenous, intraperitoneal, or intrapleural chemotherapy or biological
      treatments, and reported PFS or health-related quality of life. Data Sources: For
      this systematic review and quantitative analysis of randomized clinical trials of
      patients with cancer, we searched Medline, Embase, and the Cochrane Central
      Register of Controlled Trials from January 1, 2000, through May 4, 2016. Study
      Selection: Paired reviewers independently screened citations, extracted data, and
      assessed risk of bias of included studies. Data Extraction and Synthesis: We
      examined the association of difference in median PFS duration (in months) between
      treatment groups with difference in global, physical, and emotional HRQoL scores
      between groups (standardized to a range of 0-100, with higher scores representing
      better HRQoL) using weighted simple regressions. Main Outcome and Measure: The
      association between PFS duration and HRQoL. Results: Of 35 960 records screened,
      52 articles reporting on 38 randomized clinical trials involving 13 979 patients
      across 12 cancer types using 6 different HRQoL instruments were included. The
      mean (SD) difference in median PFS between the intervention and the control arms
      was 1.91 (3.35) months. The mean (SD) differences in change of HRQoL adjusted to
      per-month values were -0.39 (3.59) for the global domain, 0.26 (5.56) for the
      physical domain, and 1.08 (3.49) for the emotional domain. The slope of the
      association between the difference in median PFS and the difference in change for
      global HRQoL (n = 30 trials) was 0.12 (95% CI, -0.27 to 0.52); for physical HRQoL
      (n = 20 trials) it was -0.20 (95% CI, -0.62 to 0.23); and for emotional HRQoL (n
      = 13 trials) it was 0.78 (95% CI, -0.05 to 1.60). Conclusions and Relevance: We
      failed to find a significant association between PFS and HRQoL in cancer clinical
      trials. These findings raise questions regarding the assumption that
      interventions prolonging PFS also improve HRQoL in patients with cancer.
      Therefore, to ensure that patients are truly obtaining important benefit from
      cancer therapies, clinical trial investigators should measure HRQoL directly and
      accurately, ensuring adequate duration and follow-up.

PMID- 30285083
TI  - Physical Activity Predicts Population-Level Age-Related Differences in Frontal
      White Matter.
AB  - Physical activity has positive effects on brain health and cognitive function
      throughout the life span. Thus far, few studies have examined the effects of
      physical activity on white matter microstructure and psychomotor speed within the
      same, population-based sample (critical if conclusions are to extend to the wider
      population). Here, using diffusion tensor imaging and a simple reaction time task
      within a relatively large population-derived sample (N = 399; 18-87 years) from
      the Cambridge Centre for Ageing and Neuroscience (Cam-CAN), we demonstrate that
      physical activity mediates the effect of age on white matter integrity, measured
      with fractional anisotropy. Higher self-reported daily physical activity was
      associated with greater preservation of white matter in several frontal tracts,
      including the genu of corpus callosum, uncinate fasciculus, external capsule, and
      anterior limb of the internal capsule. We also show that the age-related slowing
      is mediated by white matter integrity in the genu. Our findings contribute to a
      growing body of work, suggesting that a physically active lifestyle may protect
      against age-related structural disconnection and slowing.

PMID- 30285084
TI  - Large-scale comparative assessment of computational predictors for lysine post
      translational modification sites.
AB  - Lysine post-translational modifications (PTMs) play a crucial role in regulating
      diverse functions and biological processes of proteins. However, because of the
      large volumes of sequencing data generated from genome-sequencing projects,
      systematic identification of different types of lysine PTM substrates and PTM
      sites in the entire proteome remains a major challenge. In recent years, a number
      of computational methods for lysine PTM identification have been developed. These
      methods show high diversity in their core algorithms, features extracted and
      feature selection techniques and evaluation strategies. There is therefore an
      urgent need to revisit these methods and summarize their methodologies, to
      improve and further develop computational techniques to identify and characterize
      lysine PTMs from the large amounts of sequence data. With this goal in mind, we
      first provide a comprehensive survey on a large collection of 49 state-of-the-art
      approaches for lysine PTM prediction. We cover a variety of important aspects
      that are crucial for the development of successful predictors, including
      operating algorithms, sequence and structural features, feature selection, model
      performance evaluation and software utility. We further provide our thoughts on
      potential strategies to improve the model performance. Second, in order to
      examine the feasibility of using deep learning for lysine PTM prediction, we
      propose a novel computational framework, termed MUscADEL (Multiple Scalable
      Accurate Deep Learner for lysine PTMs), using deep, bidirectional, long short
      term memory recurrent neural networks for accurate and systematic mapping of
      eight major types of lysine PTMs in the human and mouse proteomes. Extensive
      benchmarking tests show that MUscADEL outperforms current methods for lysine PTM
      characterization, demonstrating the potential and power of deep learning
      techniques in protein PTM prediction. The web server of MUscADEL, together with
      all the data sets assembled in this study, is freely available at
      http://muscadel.erc.monash.edu/. We anticipate this comprehensive review and the
      application of deep learning will provide practical guide and useful insights
      into PTM prediction and inspire future bioinformatics studies in the related
      fields.

PMID- 30285086
TI  - Commentary on: Botulinum Toxin Treatment for Mild to Moderate Platysma Bands: A
      Systematic Review of Efficacy, Safety, and Injection Technique.

PMID- 30285085
TI  - Instability of the mitochondrial alanyl-tRNA synthetase underlies fatal infantile
      onset cardiomyopathy.
AB  - Recessively-inherited variants in AARS2 (NM_020745.2) encoding mitochondrial
      alanyl-tRNA synthetase (mt-AlaRS) were first described in patients presenting
      with fatal infantile cardiomyopathy and multiple oxidative phosphorylation
      defects. To date, all described patients with AARS2-related fatal infantile
      cardiomyopathy are united by either a homozygous or compound heterozygous
      c.1774C>T (p.Arg592Trp) missense founder mutation that is absent in patients with
      other AARS2-related phenotypes. We describe the clinical, biochemical and
      molecular investigations of two unrelated boys presenting with fatal infantile
      cardiomyopathy, lactic acidosis and respiratory failure. Oxidative histochemistry
      showed cytochrome c oxidase (COX)-deficient fibres in skeletal and cardiac
      muscle. Biochemical studies showed markedly decreased activities of mitochondrial
      respiratory chain complexes I and IV with a mild decrease of complex III activity
      in skeletal and cardiac muscle. Using next-generation sequencing, we identified a
      c.1738C>T (p.Arg580Trp) AARS2 variant shared by both patients that was in trans
      with a loss-of-function heterozygous AARS2 variant; a c.1008dupT (p.Asp337*)
      nonsense variant or an intragenic deletion encompassing AARS2 exons 5-7.
      Interestingly, our patients did not harbour the p.Arg592Trp AARS2 founder
      mutation. In silico modelling of the p.Arg580Trp substitution suggested a
      deleterious impact on protein stability and folding. We confirmed markedly
      decreased mt-AlaRS protein levels in patient fibroblasts, skeletal and cardiac
      muscle, although mitochondrial protein synthesis defects were confined to
      skeletal and cardiac muscle. In vitro data showed that the p.Arg580Trp variant
      had a minimal effect on activation, aminoacylation or misaminoacylation
      activities relative to wild-type mt-AlaRS, demonstrating that instability of mt
      AlaRS is the biological mechanism underlying the fatal cardiomyopathy phenotype
      in our patients.

PMID- 30285087
TI  - Shedding light into the relevance of telomeres in human reproduction and male
      factor infertility.
AB  - Sperm telomere length (STL) is a promising new parameter for sperm quality
      analysis that may elucidate the molecular mechanisms underlying the idiopathic
      cases of male factor infertility, which represent almost half of all the male
      factor infertility cases worldwide. Telomeres consist of nucleoprotein structures
      present at the ends of eukaryotic chromosomes, whose protective functions
      maintain the genomic stability. Their role in reproduction includes an active
      intervention during gametogenesis, fertilization and preimplantation embryo
      development. In consonance, studies have shown that compromised telomere
      homeostasis is associated with male infertility. Since critically short telomeres
      have their function affected, assessing STL may be a fast and economic method for
      sperm quality analysis and expectantly contribute to improve the success of
      fertility treatments. This hypothesis is supported by several reports associating
      STL with seminal parameters, genome integrity and clinical outcomes. However,
      there are other studies in the literature that do not demonstrate these
      associations. Additionally, it is still not clear whether the lengthening
      mechanisms of telomeres occurring during early embryo development resume the
      inherited telomere length. Further research it is essential to clarify the
      suitability of STL as a biomarker for male infertility, before it could be
      routinely implemented in medically assisted reproduction centers. Understanding
      the molecular mechanisms underlying STL function and dynamics will provide us new
      insights into the origins of male infertility and a new useful tool as an outcome
      predictor for assisted reproduction.

PMID- 30285088
TI  - Association between dietary patterns and metabolic syndrome in the selected
      population of Polish adults-results of the PURE Poland Study.
AB  - Background: Dietary pattern (DP) analysis is a statistical method used to
      evaluate the comprehensive effect of the diet on health. The aim of the study was
      to assess the relationship between DPs derived in selected population of Lower
      Silesia and the prevalence of metabolic syndrome (MS) and its components.
      Methods: Study group consisted of 1634 individuals enrolled in the Prospective
      Urban and Rural Epidemiological Study Poland. Dietary intake was estimated using
      the data from the Food Frequency Questionnaire. DPs were identified using
      principal component analysis. MS prevalence was evaluated based on the criteria
      accepted by International Diabetes Federation, American Heart Association and
      National Heart, Lung and Blood Institute in 2009. Results: Three DPs were
      identified. The percentage of individuals with MS was lower in the upper quartile
      (Q) of the 'fruit & vegetables' DP in comparison with Q1 (40.4 vs. 48.9%).
      Inverse relationship was observed for 'Western' (Q4 vs. Q1: 50.7 vs. 40.8%) and
      'traditional' DPs (51.0 vs. 38.3%). After adjusting for potential confounders, in
      Q4 of 'traditional' DP higher risk for central obesity was observed compared to
      Q1 (OR 1.52; 95% CI: 1.10-2.12). Individuals in Q3 of 'fruit & vegetables' DP had
      lower risk for raised blood pressure in comparison with the bottom Q (OR 0.54;
      95% CI: 0.36-0.82). Conclusions: DP analysis allows to evaluate the synergistic
      effect of the diet on the MS prevalence. 'Fruit & vegetables' DP, in contrast to
      'Western' and 'traditional' DPs, was negatively associated with the prevalence of
      MS and its components in the study group.

PMID- 30285089
TI  - Commentary on: Long-Term Outcomes in Breast Augmentation in Trans-Women: A 20
      Year Experience.

PMID- 30285090
TI  - Meaningful Change Estimates for the Late-Life Function and Disability Instrument
      in Older Adults.
AB  - Background: The Late-Life Function and Disability Instrument (LLFDI) is a well
      validated and frequently used patient-reported outcome for older adults. The aim
      of this study was to estimate the minimal clinically important difference of the
      LLFDI-Function Component (LLFDI-FC) and its subscales among community-dwelling
      older adults with mobility limitations. Methods: We performed a secondary
      analysis of the Boston Rehabilitative Impairment Study of the Elderly, a
      longitudinal cohort study of older adults with mobility limitations residing in
      the community. The minimal clinically important difference for each LLFDI-FC
      scale over 1 year of follow-up was estimated using both anchor- and distribution
      based methods, including mean change scores on a patient-reported global rating
      of change in function scale, the standard error of measurement, and the minimal
      detectable change with 90% confidence. Results: Data from 320 older adults were
      used in the analysis (mean age 76 years, 69% female, mean of four chronic
      conditions). Meaningful change estimates for "small change" based on the global
      rating of change and standard error of measurement were 2, 3, 4, and 4 points for
      the LLFDI-FC overall function scale and basic lower-extremity, advanced lower
      extremity, and upper-extremity subscales, respectively. Estimates for
      "substantial change" based on the global rating of change and minimal detectable
      change with 90% confidence were 5, 6, 9, and 10 points for the overall function
      scale and basic lower-extremity, advanced lower-extremity, and upper-extremity
      subscales, respectively. Conclusion: This study provides the first minimal
      clinically important difference estimates for the LLFDI-FC, a widely used patient
      reported measure of function. These values can be used to interpret the outcomes
      of longitudinal investigations of functional status in similar populations of
      community-dwelling older adults.

PMID- 30285091
TI  - Specific growth conditions induce a Streptococcus pneumoniae non-mucoidal, small
      colony variant and determine the outcome of its co-culture with Haemophilus
      influenzae.
AB  - Haemophilus influenzae and Streptococcus pneumoniae are known aetiologic agents
      of chronic otitis media, frequently as a multispecies infection. In this study,
      we show that the outcome of H. influenzae/S. pneumoniae interactions is dependent
      on the nutrient source. In continuous culture containing chemically defined media
      with lactose, S. pneumoniae was non-viable in mono-culture, and in co-culture
      remained non-viable until 288 h. With glucose, S. pneumoniae became non-viable in
      mono-culture, but uniquely existed in 3 distinct states in co-culture: parental
      cells (until 24 h), a dormant state until 336 h and its re-emergence as a non
      mucoidal, small colony variant (SCV). The S. pneumoniae SCV was stable and whole
      genome sequencing showed three major single nucleotide polymorphisms in the SCV
      cells-cap3A (capsule biosynthesis pathway), fpg (DNA glycosylase of the DNA
      repair mechanism) and glutamate-5-kinase. Previously, fpg mutants have shown
      increased mutator rates, permitting bacterial survival against host-generated
      stresses. Transcriptomics showed these SCV cells up-regulated sugar transporters
      and toxin/antitoxin systems. An animal model revealed a reduced survival in the
      lungs and ear by SCV cells. This is the first study documenting the effect of
      carbon source and the development of a distinct S. pneumoniae cell type during H.
      influenzae/S. pneumoniae interactions.

PMID- 30285092
TI  - Strength endurance training but not intensive strength training reduces
      senescence-prone T-cells in peripheral blood in community-dwelling elderly women.
AB  - Ageing is characterized by a progressive decline in immune function known as
      immunosenescence (IS). While the causes of IS are likely to be multi-factorial,
      an age-associated accumulation of senescent T-cells and decreased naive T-cell
      repertoire are key contributors to the phenomenon. On the other hand, there is a
      growing consensus that physical exercise may improve immune response in ageing.
      However, the optimum training modality required to obtain beneficial adaptations
      in older subjects is lacking. Therefore, we aimed to investigate the effects of
      exercise modality on T-cell phenotypes in older women. 100 women (aged >=65
      years) were randomized to either intensive strength training (80% of one
      repetition maximum (1RM)), strength endurance training (SET, 40% 1RM), or control
      (stretching exercise) for 2-3 times/week during 6 weeks. The T-cell percentages
      and absolute counts were determined using flow cytometry and hematology analyzer.
      C-reactive protein was measured using immunonephelometry. We report for the first
      time that 6 weeks of SET significantly decreased the basal percentage and
      absolute counts of senescence-prone T-cells, which was positively related to the
      number of training sessions performed. Conceivably, training protocols with many
      repetitions - at a sufficiently high external resistance - might assist the
      reduction of senescence-prone T-cells in older women.

PMID- 30285093
TI  - Alterations of sex determination pathway in the genital ridges of males with
      limited Y chromosome genes.
AB  - We previously demonstrated that in the mouse only two Y chromosome genes are
      required for a male to produce an offspring with the help of assisted
      reproduction technologies (ART): testis determinant Sry and spermatogonial
      proliferation factor Eif2s3y. Subsequently, we have shown that the function of
      these genes can be replaced by transgenic overexpression of their homologues,
      autosomally encoded Sox9 and X-chromosome encoded Eif2s3x. Males with Y
      chromosome contribution limited to two (XEif2s3yOSry), one (XEif2s3yOSox9 and
      XOSry, Eif2s3x) and no genes (XOSox9, Eif2s3x) produced haploid germ cells and
      sired offspring after ART. However, despite successful assisted reproductive
      outcome, they had smaller testes and displayed abnormal development of the
      seminiferous epithelium and testicular interstitium. Here we explored whether
      these testicular defects originated from altered pro-testis and pro-ovary factor
      signaling in genital ridges at the time of sex determination. Timed-pregnancies
      were generated to obtain transgenic XEif2s3yOSry, XEif2s3yOSox9, XOSry, Eif2s3x,
      XOSox9, Eif2s3x and wild-type XX and XY fetuses at 12.5 days post coitum.
      Dissected genital ridges were assessed for their morphology and anatomy, and
      expression of pro-testis and pro-ovary transcripts. All transgenic males
      displayed incomplete masculinization of gonadal shape, impaired development of
      testicular cords and gonadal vasculature, and decreased expression of factors
      promoting male pathway. Fetal gonad masculinization was more effective when sex
      determination was driven by the Sry transgene, in the presence of Y chromosome
      genes, and to a lesser extent a double dosage of X genes. The study adds to the
      understanding of the role of Y chromosome genes and their homologues during sex
      determination.

PMID- 30285094
TI  - Appendectomy for Therapy-Refractory Ulcerative Colitis Results in Pathological
      Improvement of Colonic Inflammation: Short-Term Results of the PASSION Study.
AB  - Background and Aims: The objective of this study was to examine the modulating
      effect of an appendectomy on the disease course of therapy-refractory ulcerative
      colitis [UC] patients, and to analyse appendiceal pathological characteristics
      predictive of pathological response. Methods: Patients with therapy-refractory
      UC, and referred for proctocolectomy, were invited to undergo laparoscopic
      appendectomy first. The primary end points were clinical response after 3 and 12
      months. Secondary end points were endoscopic remission, failure, and pathologic
      response. Appendiceal specimens, and pre- and post-operative biopsies were
      histologically graded according to the validated Geboes score. Results: Thirty
      patients [53% male] with a median age of 40 (interquartile range [IQR], 33-47)
      underwent appendectomy, with a median preoperative total Mayo score of 9 [IQR, 8
      11]. After 12 months, 9 patients [30%] had lasting clinical response, of whom 5
      [17%] were in endoscopic remission. Pathological evaluation was possible in 28
      patients. After a median of 13.0 weeks [range 7-51], pathological response was
      seen in 13 patients [46%], with a median decrease of 2 points [range 1-3].
      Appendiceal inflammation was highly predictive of pathological response when
      compared with no inflammation or extensive ulcerations [85% vs 20%, p = 0.001].
      Conclusions: Appendectomy was effective in one-third of therapy-refractory UC
      patients, with a substantial proportion of patients demonstrating complete
      endoscopic remission after 1 year. Pathological response was seen in almost 50%
      of patients and was related to active inflammation in the appendix, limited
      disease, and shorter disease duration. These early results suggest that there is
      a UC patient group that may benefit from appendectomy.

PMID- 30285095
TI  - Bacillus wiedmannii biovar thuringiensis: A Specialized Mosquitocidal Pathogen
      with Plasmids from Diverse Origins.
AB  - Bacillus cereus sensu lato also known as B. cereus group is composed of an
      ecologically diverse bacterial group with an increasing number of related
      species, some of which are medically or agriculturally important. Numerous
      efforts have been undertaken to allow presumptive differentiation of B. cereus
      group species from one another. FCC41 is a Bacillus sp. strain toxic against
      mosquito species like Aedes aegypti, Aedes (Ochlerotatus) albifasciatus, Culex
      pipiens, Culex quinquefasciatus, and Culex apicinus, some of them responsible for
      the transmission of vector-borne diseases. Here, we report the complete genome
      sequence of FCC41 strain, which consists of one circular chromosome and eight
      circular plasmids ranging in size from 8 to 490 kb. This strain harbors six
      crystal protein genes, including cry24Ca, two cry4-like and two cry52-like, a
      cry41-like parasporin gene and multiple virulence factors. The phylogenetic
      analysis of the whole-genome sequence of this strain with molecular approaches
      places this strain into the Bacillus wiedmannii cluster. However, according with
      phenotypical characteristics such as the mosquitocidal activity due to the
      presence of Cry proteins found in the parasporal body and cry genes encoded in
      plasmids of different sizes, indicate that this strain could be renamed as B.
      wiedmannii biovar thuringiensis strain FCC41.

PMID- 30285097
TI  - A Validated GC-MS Method for the Determination of Genotoxic Impurities in
      Divalproex Sodium Drug Substance.
AB  - A specific GC-MS method has been developed, optimized and validated for the
      determination of five genotoxic impurities namely Methyl bromide (Me.-Br), Ethyl
      bromide (Et.-Br), Isopropyl bromide (Ipr.-Br), n-Propyl bromide (n-Pr.-Br) and n
      Butyl bromide (n-But.-Br) in Divalproex sodium (DPS) drug substance.
      Chromatographic separation of five genotoxic impurities was achieved on DB-1
      column (30 m * 0.32 mm, 3.0 MUm), consists of 100% dimethyl polysiloxane as
      stationary phase and passing helium carrier gas. The mass fragments (m/z) were
      selected for the quantification of Me.-Br (m/z 94), Et.-Br (m/z 108), Ipr.-Br
      (m/z 122), n-Pr.-Br (m/z 122) and n-But.-Br (m/z 136). Bromide ion (m/z 79) was
      the qualifier ion for the analytes [(Me.-Br), (Et.-Br), (Ipr.-Br), (n-Pr.-Br) and
      (n-But.-Br)]. The performance of the method was assessed by evaluating the
      specificity, linearity, sensitivity, precision and accuracy experiments. The
      established limit of detection and limit of quantification values for the
      genotoxic impurities were in the range of 0.005-0.019 MUg mL-1. The correlation
      coefficient values of the linearity experiment were in the range of 0.9947
      0.9983. The average recoveries for the accuracy were in the range of 97.6-111.3%.
      The results proved that the method is suitable for the determination of Me.-Br,
      Et.-Br, Ipr.-Br, n-Pr.-Br and n-But.-Br contents in divalproex sodium.

PMID- 30285096
TI  - A toolkit for rapid CRISPR-SpCas9 assisted construction of hexose-transport
      deficient Saccharomyces cerevisiae strains.
AB  - Hexose transporter-deficient yeast strains are valuable testbeds for the study of
      sugar transport by native and heterologous transporters. In the popular
      Saccharomyces cerevisiae strain EBY.VW4000, deletion of 21 transporters
      completely abolished hexose transport. However, repeated use of the LoxP/Cre
      system in successive deletion rounds also resulted in major chromosomal
      rearrangements, gene loss and phenotypic changes. In the present study,
      CRISPR/SpCas9 was used to delete the 21 hexose transporters in an S. cerevisiae
      strain from the CEN.PK family in only three deletion rounds, using 11 unique
      guide RNAs. Even upon prolonged cultivation, the resulting strain IMX1812 (CRISPR
      Hxt0) was unable to consume glucose, while its growth rate on maltose was the
      same as that of a strain equipped with a full set of hexose transporters.
      Karyotyping and whole-genome sequencing of the CRISPR-Hxt0 strain with Illumina
      and Oxford Nanopore technologies did not reveal chromosomal rearrangements or
      other unintended mutations besides a few SNPs. This study provides a new,
      'genetically unaltered' hexose transporter-deficient strain and supplies a CRISPR
      toolkit for removing all hexose transporter genes from most S. cerevisiae
      laboratory strains in only three transformation rounds.

PMID- 30285098
TI  - Senescent Cells Differentially Translate Senescence-Related mRNAs Via Ribosome
      Heterogeneity.
AB  - The ribosome has a lateral stalk which consists of rpLP0, rpLP1, and rpLP2. One
      of these proteins, rpLP2, is decreased in translating ribosome when cellular
      senescence is induced. Y-box binding protein-1 (YB-1) is also reduced in
      polysomal fraction of senescent cells. We discovered that rpLP2 depletion in the
      ribosome can cause the detachment of YB-1 in polysomes and that it is linked to
      cellular senescence. Our results also revealed that a decrement of CK2alpha or
      GRK2 in senescent cells induced an increment of unphosphorylated rpLP2, resulting
      in release of YB-1 from polysomes. This heterogeneous senescent ribosome has
      different translational efficiencies for some senescence-related genes. We also
      showed that the decrease of rpLP1/rpLP2 and YB-1 in senescent ribosomes was not
      specific to cell type or stress type and the same phenomenon was also observed in
      aged mouse livers regardless of gender. Taken together, our results suggest that
      the senescent ribosome complex appears to have low levels of rpLP1/rpLP2 and YB
      1, resulting in altered translational efficiency for senescence-related genes.

PMID- 30285099
TI  - Neoatherosclerosis after drug-eluting stent implantation: a novel clinical and
      therapeutic challenge.
AB  - The recognition that obstructive disease of the epicardial coronary arteries,
      causing ischemic heart disease, can be treated with a percutaneous coronary
      intervention (PCI) has been a major discovery in cardiology in the last 40 years
      contributing, in particular, to the reduction of mortality associated to acute
      myocardial infarction (AMI). However, even in the era of drug-eluting stent (DES)
      implantation, a sizable proportion of patients who undergo PCI may develop late
      or very late post-implantation complications, that occur in the form of
      restenosis, neoatherosclerosis and/or in-stent thrombosis. Such complications are
      clinically relevant since they can cause AMI and negatively impact on the
      outcome. The underlying pathophysiological mechanisms are complex but related to
      inhibition of neointimal proliferation by DES that, on the hand, reduces the rate
      of in-stent restenosis, but, on the other hand, causes dysfunctional vessel
      healing, persistent inflammation, platelet activation and adverse immunologic
      responses. Multiple approaches have been developed or are under evaluation to
      target DES-related complications including pharmacotherapy, procedure-related
      imaging methods, novel stent designs and drug-delivery methods.The aim of this
      review is to provide an update on the latest preclinical, translational and
      clinical pharmacotherapeutic developments in this setting that target novel
      cellular mechanisms and pathways that might contribute to neoatherosclerosis. Due
      to the importance of secondary prevention in the reduction of DES-associated
      complications, this review also provides a short overview of pharmacologic agents
      that are established or currently being investigated in this regard.

PMID- 30285100
TI  - Commentary on: Evaluation of Antibiotic-Impregnated Mesh in Preventing the
      Recurrence of Capsular Contracture.

PMID- 30285101
TI  - RAB8A GTPase regulates spindle migration and Golgi apparatus distribution via
      ROCK-mediated actin assembly in mouse oocyte meiosis.
AB  - Actin filaments are widely involved in multiple cellular processes in oocyte
      meiosis, such as spindle migration and polar body extrusion. The actin nucleators
      like Arp2/3 complex and formins are the most recognized molecules for actin
      assembly in oocytes. In the present study, we report that the vesicle trafficking
      factor, RAB8A GTPase, is a new regulator critical for actin assembly in meiosis.
      Our results showed that RAB8A was localized at both the spindle periphery and
      cortex in mouse oocytes, which was similar to the localization patterns of actin
      filaments. RAB8A depletion caused spindle migration defects and the failure of
      polar body extrusion, which could have been due to decreases in both cytoplasmic
      and cortical actin filaments in oocytes. Based on mass spectrometry analysis, we
      showed that RAB8A promoted actin assembly through its modulation on the ROCK-LIMK
      signaling pathway. Moreover, we demonstrated that RAB8A colocalized and
      interacted with GM130 at the spindle periphery and that RAB8A depletion caused
      the disruption of GM130-docked Golgi distribution. Taken together, our data
      indicated that RAB8A was required for Golgi distribution, spindle migration, and
      polar body extrusion via ROCK-mediated actin assembly in mouse oocyte meiosis.

PMID- 30285102
TI  - Robust EEG-based cross-site and cross-protocol classification of states of
      consciousness.
AB  - Determining the state of consciousness in patients with disorders of
      consciousness is a challenging practical and theoretical problem. Recent findings
      suggest that multiple markers of brain activity extracted from the EEG may index
      the state of consciousness in the human brain. Furthermore, machine learning has
      been found to optimize their capacity to discriminate different states of
      consciousness in clinical practice. However, it is unknown how dependable these
      EEG markers are in the face of signal variability because of different EEG
      configurations, EEG protocols and subpopulations from different centres
      encountered in practice. In this study we analysed 327 recordings of patients
      with disorders of consciousness (148 unresponsive wakefulness syndrome and 179
      minimally conscious state) and 66 healthy controls obtained in two independent
      research centres (Paris Pitie-Salpetriere and Liege). We first show that a non
      parametric classifier based on ensembles of decision trees provides robust out-of
      sample performance on unseen data with a predictive area under the curve (AUC) of
      ~0.77 that was only marginally affected when using alternative EEG configurations
      (different numbers and positions of sensors, numbers of epochs, average AUC =
      0.750 +/- 0.014). In a second step, we observed that classifiers based on
      multiple as well as single EEG features generalize to recordings obtained from
      different patient cohorts, EEG protocols and different centres. However, the
      multivariate model always performed best with a predictive AUC of 0.73 for
      generalization from Paris 1 to Paris 2 datasets, and an AUC of 0.78 from Paris to
      Liege datasets. Using simulations, we subsequently demonstrate that multivariate
      pattern classification has a decisive performance advantage over univariate
      classification as the stability of EEG features decreases, as different EEG
      configurations are used for feature-extraction or as noise is added. Moreover, we
      show that the generalization performance from Paris to Liege remains stable even
      if up to 20% of the diagnostic labels are randomly flipped. Finally, consistent
      with recent literature, analysis of the learned decision rules of our classifier
      suggested that markers related to dynamic fluctuations in theta and alpha
      frequency bands carried independent information and were most influential. Our
      findings demonstrate that EEG markers of consciousness can be reliably,
      economically and automatically identified with machine learning in various
      clinical and acquisition contexts.

PMID- 30285104
TI  - Deep remission with vedolizumab in patients with moderately to severely active
      ulcerative colitis: a GEMINI 1 post hoc analysis.
AB  - Background and Aims: This GEMINI 1 post hoc analysis evaluated vedolizumab
      efficacy for inducing deep remission in patients with ulcerative colitis and
      correlation between vedolizumab trough concentrations and deep remission rates.
      Methods: Week 6 vedolizumab responders were re-randomised to placebo or
      vedolizumab every 8 or 4 weeks. Deep remission at Week 52 was measured using 4
      different definitions (from most to least stringent): (1) Mayo Clinic endoscopic
      score=0, rectal bleeding score=0 and decrease or no change from baseline in stool
      frequency score; (2) endoscopic score <=1, rectal bleeding score=0 and stool
      frequency score=0; (3) endoscopic score <=1, rectal bleeding score=0, decrease or
      no change from baseline stool frequency score, and total score [endoscopic score
      + rectal bleeding score + stool frequency score] <=1; (4) endoscopic score <=1,
      rectal bleeding score=0 and stool frequency score <=1. Steady-state trough
      vedolizumab serum concentrations were evaluated. Results: At Week 6, 373
      vedolizumab responders were re-randomised to maintenance placebo (n=126) or
      vedolizumab every 8 (n=122) or 4 (n=125) weeks. Significantly more vedolizumab
      patients achieved deep remission at Week 52 for the most (placebo 8.7%, every 8
      weeks 27.0% [P=0.0001], every 4 weeks 28.0% [P<0.0001] and least (placebo 15.9%,
      every 8 weeks 43.4% [P<0.0001], every 4 weeks 43.2% [P<0.0001]) stringent
      definitions. Patients with higher vedolizumab trough concentration quartiles had
      higher deep remission rates (all definitions), versus those with the lowest
      quartile or who received placebo. Conclusion: Vedolizumab was associated with
      significantly higher deep remission rates than placebo at Week 52, regardless of
      deep remission definition. (NCT00783718).

PMID- 30285103
TI  - Color statistics of objects, and color tuning of object cortex in macaque monkey.
AB  - We hypothesized that the parts of scenes identified by human observers as
      "objects" show distinct color properties from backgrounds, and that the brain
      uses this information towards object recognition. To test this hypothesis, we
      examined the color statistics of naturally and artificially colored objects and
      backgrounds in a database of over 20,000 images annotated with object labels.
      Objects tended to be warmer colored (L-cone response > M-cone response) and more
      saturated compared to backgrounds. That the distinguishing chromatic property of
      objects was defined mostly by the L-M post-receptoral mechanism, rather than the
      S mechanism, is consistent with the idea that trichromatic color vision evolved
      in response to a selective pressure to identify objects. We also show that
      classifiers trained using only color information could distinguish animate versus
      inanimate objects, and at a performance level that was comparable to
      classification using shape features. Animate/inanimate is considered a
      fundamental superordinate category distinction, previously thought to be computed
      by the brain using only shape information. Our results show that color could
      contribute to animate/inanimate, and likely other, object-category assignments.
      Finally, color-tuning measured in two macaque monkeys with functional magnetic
      resonance imaging (fMRI), and confirmed by fMRI-guided microelectrode recording,
      supports the idea that responsiveness to color reflects the global functional
      organization of inferior temporal cortex, the brain region implicated in object
      vision. More strongly in IT than in V1, colors associated with objects elicited
      higher responses than colors less often associated with objects.

PMID- 30285105
TI  - A novel solution for freezing small numbers of spermatozoa using a sperm
      vitrification device.
AB  - STUDY QUESTION: Does a novel sperm vitrification device (SpermVD) provide an
      efficient method for freezing a small number of human spermatozoa from men
      suffering from non-obstructive azoospermia? SUMMARY ANSWER: The novel SpermVD is
      an efficient and simple carrier method for freezing a small number of spermatozoa
      in low-volume droplets, reducing post-thaw search time from hours to minutes,
      allowing a 96% recovery rate and leading to successful use of sperm for
      fertilization. WHAT IS KNOWN ALREADY: Previous methods for cryopreservation of
      small numbers of human spermatozoa (e.g. mini-straws, ICSI pipette, alginate
      beads, cryoloop) have been proposed as a solution for cases of severe male
      infertility. Many drawbacks have prevented their widespread use, including
      cumbersome preparation and sperm retrieval procedures, and the fact that the
      thawed spermatozoa are not immediately available for micromanipulation and
      required additional treatment which posed excess risk of harm. STUDY DESIGN,
      SIZE, DURATION: We conducted a feasibility experiment of the novel SpermVD and a
      prospective cohort study of ICSI cycles in men suffering from non-obstructive
      azoospermia in two outpatient fertility IVF clinics, from 2015 through 2017.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent extended
      ejaculate search prior to the day of oocyte retrieval, and any single motile
      spermatozoa found was transferred to 0.8 MUl droplets of 1:1 washing
      medium/cryoprotectant on the SpermVD, then plunged into liquid nitrogen for
      cryopreservation. In patients with non-obstructive azoospermia who underwent
      surgical TESE, both the motile and immotile spermatozoa found underwent
      cryopreservation using the SpermVD. On the day of oocyte retrieval, the SpermVD
      was thawed, directly transfered to the ICSI plate and retrieved spermatozoa were
      used for the ICSI procedure. MAIN RESULTS AND THE ROLE OF CHANCE: The prospective
      cohort included 44 cases. We used the SpermVD to vitrify 631 spermatozoa, of
      which 540 (86%) were motile. The average number of frozen spermatozoa per patient
      was 14.3 +/- 9.3. After thawing, we retrieved 607 spermatozoa, producing a
      recovery rate of 96%. The average number of thawed spermatozoa was 13.8 +/- 9.2.
      The recovery of 180 thawed motile sperm accounted for 33% of all frozen motile
      spermatozoa. The fertilization rate was 59%. Of 44 oocyte retrieval procedures,
      24 (55%) clinical pregnancies were achieved. The delivery rate (not including
      three ongoing pregnancies) was 32% and the miscarriage rate was 29%. LIMITATIONS,
      REASONS FOR CAUTION: Although we presented the SpermVD on 44 cases, a larger
      cohort would provide more information. Moreover, we cryopreserved only motile
      sperm from the ejaculates and not immotile sperm, thus limiting the knowledge
      regarding the efficacy of the VD for immotile sperm from this source. WIDER
      IMPLICATIONS OF THE FINDINGS: The novel SpermVD is a simple efficient carrier,
      optimizing the protocol for freezing a small number of spermatozoa. It may allow
      for the routine use of frozen spermatozoa after TESE for men suffering from non
      obstructive azoospermia and thus avoid repeated TESE surgeries. Furthermore, in
      cases of non-obstructive azoospermia, routine cryopreservation of the retrieved
      spermatozoa prior to the IVF cycle may avoid the risk of cycle cancelation and
      thus decrease the number of unnecessary oocyte retrieval procedures. STUDY
      FUNDING/COMPETING INTEREST(S): There was no external funding. There are no
      competing interests. TRIAL REGISTRATION NUMBER: IRB no 00119-16-ASMC.

PMID- 30285106
TI  - Impact of HIV-1 primary drug resistance on the efficacy of a first-line
      antiretroviral regimen in the blood of newly diagnosed individuals in Bamako,
      Mali.
AB  - Background: To achieve the 90-90-90 targets assigned by UNAIDS, it is crucial to
      monitor ART in HIV-1-infected patients, especially in resource-limited countries.
      Objectives: To evaluate the immunovirological response after 12 months of ART in
      newly HIV-1-diagnosed people in Bamako, Mali; to determine primary and acquired
      resistance rates to antiretroviral drugs; and to evaluate the impact of primary
      resistance on the efficacy of ART. Patients and methods: One hundred and nineteen
      HIV-1-infected people (88.2% women; median age 34 years) were enrolled between
      January and June 2014. HIV-1 RNA loads (Abbott RealTime HIV-1 assay) were tested
      in the blood before and at months 3, 6 and 12 after initiation of ART. Primary
      and acquired resistances to ART were evaluated by the ViroseqTM HIV-1 genotyping
      assay. Results: During the study, 8.4% of people died and 37% were lost to follow
      up. After 1 year of ART, an undetectable HIV-1 RNA viral load was found in 87.7%
      of cases. The overall rate of primary drug resistance mutations was 17.5% (3.2%,
      15.9% and 0% for NRTIs, NNRTIs and PIs, respectively). These mutations were not
      associated with either higher mortality rates or larger numbers of virological
      failures. The acquired resistance rate was estimated at 3.1%. Conclusions: Our
      study showed a high primary resistance level and a huge proportion of people non
      adherent to the treatment programme. Reassuringly, almost 90% virological success
      and a low level of acquired mutations were observed in adherent people at month
      12. Reinforced education, regular virological monitoring and early HIV-1
      diagnosis may help to improve retention in the care system.

PMID- 30285108
TI  - CHCHD2 accumulates in distressed mitochondria and facilitates oligomerization of
      CHCHD10.

PMID- 30285107
TI  - Genetic Diversity in the Progeny of Commercial Australian Queen Honey Bees
      (Hymenoptera: Apidae) Produced in Autumn and Early Spring.
AB  - Honey bee [Apis mellifera L. (Hymenoptera: Apidae)] queens are polyandrous,
      mating with an average 12 males (drones). Polyandry has been shown to confer
      benefits to queens and the colonies they head, including avoidance of inviable
      brood that can arise via sex locus homozygosity, increased resilience to pests
      and pathogens, and increased survival and productivity, leading to improved
      colony-level fitness. Queens with an effective mating frequency (ke) greater than
      7 are considered adequately mated, whereas queens that fall below this threshold
      head colonies that have increased likelihood of failure and may be less
      productive for beekeepers. We determined ke in queens produced in early Spring
      and Autumn by five Australian commercial queen producers to determine whether the
      queens they produced were suitably mated. Drone populations are low at these
      times of year, and therefore, there is an increased risk that queens would fall
      below the ke > 7 threshold. We found that 33.8% of Autumn-produced queens did not
      meet the threshold, whereas 93.8% of Spring queens were adequately mated. The
      number of colonies contributing drones to the mating pool was similarly high in
      both seasons, suggesting that although many colonies have drones, their numbers
      may be decreased in Autumn and management strategies may be required to boost
      drone numbers at this time. Finally, queens had similar levels of homozygosity to
      workers, and inbreeding coefficients were very low, suggesting that inbreeding is
      not a problem.

PMID- 30285109
TI  - LncRNADisease 2.0: an updated database of long non-coding RNA-associated
      diseases.
AB  - Mounting evidence suggested that dysfunction of long non-coding RNAs (lncRNAs) is
      involved in a wide variety of diseases. A knowledgebase with systematic
      collection and curation of lncRNA-disease associations is critically important
      for further examining their underlying molecular mechanisms. In 2013, we
      presented the first release of LncRNADisease, representing a database for
      collection of experimental supported lncRNA-disease associations. Here, we
      describe an update of the database. The new developments in LncRNADisease 2.0
      include (i) an over 40-fold lncRNA-disease association enhancement compared with
      the previous version; (ii) providing the transcriptional regulatory relationships
      among lncRNA, mRNA and miRNA; (iii) providing a confidence score for each lncRNA
      disease association; (iv) integrating experimentally supported circular RNA
      disease associations. LncRNADisease 2.0 documents more than 200 000 lncRNA
      disease associations. We expect that this database will continue to serve as a
      valuable source for potential clinical application related to lncRNAs.
      LncRNADisease 2.0 is freely available at http://www.rnanut.net/lncrnadisease/.

PMID- 30285110
TI  - Variegated yet non-random rod and cone photoreceptor disease patterns in RPGR
      ORF15-associated retinal degeneration.

PMID- 30285111
TI  - Prevalence of and factors associated with under-5 mortality in South Asia.
AB  - Background: This study investigated the prevalence of and the factors associated
      with under-5 mortality across five South Asian countries. Methods: Cross
      sectional pooled data from 1999 through 2014 collected from the Demographic and
      Health Survey (DHS) in five South Asian countries (Bangladesh, India, Maldives,
      Nepal and Pakistan) were used. Associations of under-5 mortality with
      sociodemographic characteristics and maternal and child factors were studied
      using the Cox proportional-hazard method. The estimates were presented as hazard
      ratios (HR) and their 95% CIs. Kaplan-Meier survival curves were used to describe
      time-to-event of under-5 survival patterns. Results: Overall, 15-year prevalence
      of under-5 mortality in South Asian countries was 10%, with Nepal having the
      highest prevalence (11.1%) and the Maldives the lowest (5%). In a multivariable
      model in pooled data, older age of mother (HR 0.70, 95% CI 0.68-0.72), being
      employed (HR 1.09, 95% CI 1.07-1.12), having a higher level of education (HR
      0.36, 95%, CI 0.32-0.40) and having a husband with higher level of education (HR
      0.74, 95% CI 0.70-0.78) were significantly associated with under-5 mortality.
      Factors associated with under-5 mortality were mostly common across countries.
      Conclusion: The prevalence of under-5 mortality is still high in South Asia. Most
      of the studied sociodemographic factors were associated with under-5 mortality
      and were common across South Asian countries.

PMID- 30285112
TI  - How lymphatic filariasis was eliminated from an urban poor setting in Santo
      Domingo, Dominican Republic.
AB  - Background: While progress has been made in the elimination of lymphatic
      filariasis, challenges that call for innovative approaches remain. Program
      challenges are increasingly observed in 'hard-to-reach' populations: urban
      dwellers, migrant populations, those living in insecurity, children who are out
      of school and areas where infrastructure is weak and education levels are low.
      'Business-as-usual' approaches are unlikely to work. Tailored solutions are
      needed if elimination goals are to be reached. This article focuses on mass drug
      administrations (MDAs) in urban settings. Methods: We selected the urban poor
      area of Santo Domingo, Dominican Republic. With three rounds of MDA and with good
      coverage, elimination was achieved. We wanted to understand contributing factors
      to achieving good coverage. A qualitative study analyzed context, barriers and
      facilitators using a predefined framework based on review of the literature.
      Results: Results show that barriers commonly reported in urban settings were
      present (population density, lack of organization in household layout, population
      mobility, violence, shortage of human resources and challenges in monitoring
      treatment coverage). Tactics used included strong visibility in the community
      leading to high levels of awareness, the use of laminated photo sheets during
      house-to-house visits and a 1:4 supervision strategy. The importance of working
      through community leadership structures and building relationships with the
      community was evident. Discussion: The approach developed here has applications
      for large-scale treatment programs for lymphatic filariasis and other diseases in
      urban settings.

PMID- 30285113
TI  - Diagnostic ability and inappropriate antibiotic prescriptions: a quasi
      experimental study of primary care providers in rural China.
AB  - Background: China has one of the highest rates of antibiotic resistance. Existing
      studies document high rates of antibiotic prescription by primary care providers
      but there is little direct evidence on clinically inappropriate use of
      antibiotics or the drivers of antibiotic prescription. Methods: To assess
      clinically inappropriate antibiotic prescriptions among rural primary care
      providers, we employed unannounced standardized patients (SPs) who presented
      three fixed disease cases, none of which indicated antibiotics. We compared
      antibiotic prescriptions of the same providers in interactions with SPs and
      matching vignettes assessing knowledge of diagnosis and treatment to assess
      overprescription attributable to deficits in diagnostic knowledge, therapeutic
      knowledge and factors that lead providers to deviate from their knowledge of best
      practice. Results: Overall, antibiotics were inappropriately prescribed in
      221/526 (42%) SP cases. Compared with SP interactions, prescription rates were
      29% lower in matching clinical vignettes (42% versus 30%, P < 0.0001). Compared
      with vignettes assessing diagnostic and therapeutic knowledge jointly, rates were
      67% lower in vignettes with the diagnosis revealed (30% versus 10%, P < 0.0001).
      Antibiotic prescription in vignettes was inversely related to measures of
      diagnostic process quality (completion of checklists). Conclusions: Clinically
      inappropriate antibiotic prescription is common among primary care providers in
      rural China. While a large proportion of overprescription may be due to factors
      such as financial incentives tied to drug sales and perceived patient demand, our
      findings suggest that deficits in diagnostic knowledge are a major driver of
      unnecessary antibiotic prescriptions. Interventions to improve diagnostic
      capacity among providers in rural China are needed.

PMID- 30285114
TI  - Surviving in the absence of flowers: do nectar yeasts rely on overwintering
      bumblebee queens to complete their annual life cycle?
AB  - Floral nectar represents an ephemeral habitat that is restricted in time and
      space to zoophilous flowering vegetation. To survive in these habitats, nectar
      inhabiting microorganisms rely on animal vectors to disperse from one flower to
      the next. However, it remains unclear how nectar yeasts persist when flowers and
      nectar cease to be present. Here, we tested the hypothesis that hibernating
      bumblebee queens function as a reservoir for nectar yeasts in the absence of
      plants or pollinators during winter. Our results show that the nectar yeast,
      Metschnikowia reukaufii, was present in the gastrointestinal tract of wild
      bumblebee queens that emerged from hibernation and that it could persist inside
      the gut of hibernating queens under experimental conditions. However, no evidence
      for such persistence was found in the case of the second most frequent nectar
      yeast, M. gruessii. Furthermore, a phylloplane yeast that occasionally inhabits
      nectar, Rhodotorula mucilaginosa, was able to colonize the gut under experimental
      conditions. Two bumblebee-associated yeasts, Candida bombi and C. bombiphila,
      were successfully passed down generations after administration in commercial lab
      reared bumblebees. Overall, these results demonstrate that bumblebees could act
      as a reservoir for nectar yeasts during winter when floral nectar is absent.

PMID- 30285116
TI  - Commentary: JPP Student Journal Club Commentary: Strengths-Based, Clinic
      Integrated Nonrandomized Pilot Intervention to Promote Type 1 Diabetes Adherence
      and Well-Being.

PMID- 30285115
TI  - Paradoxical GH increase during OGTT is associated to first-generation
      somatostatin analogs responsiveness in acromegaly.
AB  - CONTEXT: The oral glucose tolerance test (OGTT) is considered the most useful
      method for diagnosing active acromegaly and for patient follow-up after
      neurosurgery. Despite its widespread use, only a few small studies have so far
      focused on patients' clinical features associated with different GH
      responsiveness to OGTT. OBJECTIVE: We aimed to investigate the association
      between glucose-induced GH response and endocrine profiles, clinical
      manifestations, and response to therapy in a large cohort of patients with
      acromegaly. PATIENTS: Based on GH response to the OGTT, patients were grouped as
      paradoxical (GH-Par) or non-paradoxical (GH-NPar), and their clinical and
      pathological features were compared in terms of pituitary tumor size,
      invasiveness, biochemical profiles, and response to therapy. RESULTS: The study
      concerned 496 acromegalic patients. At diagnosis, GH-Par patients (n=184) were
      older than GH-NPar patients (n=312) (mean 44.1+/-13.7 years vs 40.5+/-12.7,
      p<0.01), and had smaller tumors (0.82 vs 1.57 cm3, p<0.01), that less frequently
      invaded the cavernous sinus (15% vs 27%, p<0.01). The GH-Par group also had a
      higher basal GH per volume ratio (14.3 vs 10.5 MUg/L?cm3, p<0.05) and a lower
      incidence of hyperprolactinemia (17% vs 30%, p<0.01) than the GH-NPar patients.
      Importantly, the GH-Par group had a higher rate of remission in response to
      somatostatin analogs (52% vs 26%, p<0.01), and a more marked drop in IGF-1 and GH
      after six months of therapy. CONCLUSIONS: Our data strongly suggest that serum GH
      responsiveness to oral glucose challenge reflects some significant biological
      features of pituitary tumors and the OGTT may have some prognostic value.

PMID- 30285117
TI  - Hyperandrogenism in Female Athletes.

PMID- 30285118
TI  - Prevalence and risk factors for diabetes mellitus among adults in Ghana: a
      systematic review and meta-analysis.
AB  - Background: The prevalence and risk factors for diabetes in Ghana vary from
      location to location, yet no study has been conducted to quantitatively
      synthesize the available studies. Methods: The authors conducted a comprehensive
      literature search in Medline (PubMed), Embase, Cinahl, Web of Science, Scopus,
      African journals and grey literature. Two reviewers screened the articles for
      relevance, identified and selected studies based on inclusion and exclusion
      criteria. Methodological quality was independently assessed, using two validated
      assessment-of-bias tools. We explored study heterogeneity and performed a
      publication bias check. Results: This search yielded a total of 624 articles, of
      which 17 studies were finally selected for the qualitative review and 12 studies
      included in the meta-analysis. The overall prevalence of diabetes mellitus among
      adult Ghanaians was high at 6.46% (95% CI: 4.66-8.26%) based on the inverse
      variance random-effects model. Significant risk factors associated with diabetes
      were a family history of diabetes (OR: 3.46, 95% CI: 2.50-4.78), physical
      inactivity (OR: 3.06, 95% CI: 1.66-5.64) and age >=40 years (OR: 2.36, 95% CI:
      1.77-3.16). Conclusion: Studies with high methodological quality provided
      sufficient evidence about diabetes prevalence among adults and the associated
      significant risk factors in Ghana.

PMID- 30285119
TI  - Persistent Effects of Antenatal Synthetic Glucocorticoids on Endocrine Stress
      Reactivity from Childhood to Adolescence.
AB  - Context: Antenatal synthetic glucocorticoid (sGC) therapy has been identified as
      potent programming factor of the hypothalamic-pituitary-adrenal (HPA) axis. We
      previously observed significantly increased cortisol stress responses in 6-11-yr
      old, term-born children exposed to antenatal sGC treatment compared to controls.
      These findings clearly call for longitudinal follow-up studies to evaluate long
      term effects of antenatal sGCs, given that adolescence is marked by a significant
      shift of HPA-axis functioning. Objective: This study aimed to longitudinally
      investigate the stability of antenatal sGCs-related effects on cortisol stress
      reactivity from childhood to adolescence. Design, Setting, and Participants: To
      evaluate long-term trajectories of antenatal sGC therapy, we have longitudinally
      followed a subsample (n=44) of our children's cohort into late adolescence (14-18
      yr-old) for a second assessment of cortisol stress reactivity. To this end, 22
      adolescents with antenatal sGC exposure (dexamethasone or betamethasone) and 22
      untreated controls underwent a standardized laboratory stressor (Trier Social
      Stress Test). Results: While we observed a general increase in HPA-axis
      reactivity from childhood to adolescence (P<0.05), participants treated with
      antenatal sGCs showed significantly higher cortisol levels in response to the
      TSST compared to controls during both developmental stages (P<0.05). Furthermore,
      we observed a moderating effect of sGC treatment on rank-order stability of
      cortisol stress reactivity from childhood to adolescence (P<0.05) with a trend
      (p=0.07) for higher rank-order stability in sGC exposed individuals (r=0.37)
      compared to controls (r=-0.20). Conclusion: These findings suggest that antenatal
      sGC therapy yields long-term changes of HPA-axis reactivity that persist into
      late adolescence and may confer increased vulnerability for developing stress
      related disorders.

PMID- 30285120
TI  - Response to Letter to the Editor: "Association of Vitamin D Deficiency With
      Peripheral Arterial Disease: A Meta-Analysis of Literature Studies".

PMID- 30285122
TI  - The prevalence of midline prostatic cysts and the relationship between cyst size
      and semen parameters among infertile and fertile men.
AB  - STUDY QUESTION: When is the investigation and treatment of midline prostatic
      cysts (MPC) of clinical value in the work-up of males of infertile couples?
      SUMMARY ANSWER: With a prevalence of 10.2% in infertile men, MPC should be
      investigated according to a seminal algorithm detecting a MPC volume >0.117 ml,
      which may impair semen parameters, and could be treated to improve sperm count
      and achieve natural pregnancy. WHAT IS KNOWN ALREADY: MPC are frequent and are
      considered a correctable cause of male infertility. However, they have been
      poorly investigated in an infertility setting. In addition, no study has
      investigated clinical and ultrasound (US) characteristics of men with MPC. STUDY
      DESIGN, SIZE, DURATION: A cross-sectional analysis was carried out of 693
      consecutive subjects consulting for couple infertility from September 2012 to
      March 2017. As a control group, 103 age-matched healthy, fertile men were
      studied. Furthermore, a longitudinal evaluation of 11 infertile men undergoing
      trans-rectal ultrasonically-guided cyst aspiration (TRUCA), semen analyses 1 and
      3 months after TRUCA and a follow-up 1 year after TRUCA to assess natural
      pregnancy were performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: All subjects
      underwent, in our outpatient clinic, clinical, hormonal, scrotal and transrectal
      US evaluation and semen analysis within the same day. Of 693 males of infertile
      couples, 648 (37.1 +/- 7.9 years, mean+SD) without genetic abnormalities were
      studied, along with 103 fertile men (36.6 +/- 5.0 years). Eleven infertile men
      underwent TRUCA and were followed-up as reported above. MAIN RESULTS AND THE ROLE
      OF CHANCE: A MPC was present in 66/648 (10.2%) males of infertile couples and in
      6/103 (5.8%) fertile men. MPC occurrence and volume were higher in patients with
      severe oligo- or azoospermia than in fertile men (all P < 0.05). Infertile men
      with a MPC showed a lower seminal volume and sperm count and a higher prevalence
      of azoospermia than the rest of the infertile sample or fertile men, and a higher
      frequency of US signs suggestive of ejaculatory duct obstruction. MPC volume was
      negatively associated with total sperm count (r = -0.452, P < 0.0001). In fertile
      men, the highest MPC volume was 0.117 ml, suggesting it as a biological threshold
      not compromising semen quality. In infertile men, using receiver operating
      characteristic curve analyses, a MPC volume >0.117 ml identified subjects with
      severe oligo- or azoospermia with an overall accuracy of ~75% (both P < 0.005).
      Eleven men with infertility, semen abnormalities and large MPC (>0.250 ml)
      underwent TRUCA, which led to sperm count improvement in all patients 1 month
      after surgery. Three months after TRUCA a lower sperm count and a higher MPC
      volume than 2 months before were observed (P < 0.005 and P < 0.05, respectively),
      although improved when compared to baseline. After TRUCA a natural pregnancy
      occurred in four couples. Finally, we propose an algorithm, based on semen
      parameters, useful in identifying a MPC in males of infertile couples.
      LIMITATIONS, REASONS FOR CAUTION: Although in line with the sample size of
      previous studies (n = 7-20), the number of infertile men with MPC evaluated
      longitudinally after treatment is limited (n = 11). In addition, although a MPC
      volume >0.117 ml can negatively affect the sperm count, only MPC > 0.250 ml have
      been treated in this study. WIDER IMPLICATIONS OF THE FINDINGS: First, the
      algorithm proposed is easy to use and useful for selecting patients who can
      benefit from a prostate US in the infertility work-up. Second, a MPC volume
      <=0.117 ml may not impair semen quality, while a larger volume can lead to severe
      oligo- or azoospermia and could be treated. Third, TRUCA is effective, and
      simpler and less invasive than other surgical techniques for MPC treatment.
      Finally, since the MPC can increase in size and sperm count decrease over time
      after TRUCA, semen cryopreservation should be considered 1 month after TRUCA.
      STUDY FUNDING/COMPETING INTEREST(S): Grants from the Ministry of University and
      Scientific Research (SIR project to F.L., protocol number: RBSI14LFMQ). No
      conflicts of interest.

PMID- 30285123
TI  - Novel composite SCCmec type III element in ST239 MRSA isolated from an Indian
      hospital.

PMID- 30285121
TI  - Aquaporin-3 mediates ovarian steroid hormone-induced motility of endometrial
      epithelial cells.
AB  - STUDY QUESTION: How does aquaporin-3 (AQP3) affect endometrial receptivity?
      SUMMARY ANSWER: AQP3, which is regulated by the combination and estrogen (E2) and
      progesterone (P4), induces epithelial-mesenchymal transition (EMT) of endometrial
      epithelial cells. WHAT IS KNOWN ALREADY: Embryo implantation is an extremely
      complex process, and endometrial receptivity is essential for successful embryo
      implantation. Estrogen and progesterone regulate endometrial receptivity. AQP3,
      which is regulated by estrogen (E2), increases cell migration and invasion
      ability by regulating the expression of EMT-related factors and influencing the
      reorganization of the actin cytoskeleton. STUDY DESIGN, SIZE, DURATION: This
      study investigated the pathophysiological significance of AQP3 in human
      endometrial function during different phases of the menstrual cycle.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: AQP3 expression levels during different
      phases of the menstrual cycle were measured using immunohistochemical assays. In
      cells of different receptivity (high-receptive RL95-2 cells and low-receptive HEC
      1A cells), the expression of AQP3 was measured using western blotting, qRT-PCR
      and immunofluorescence assays. Activities of AQP3, and its regulation by E2 and
      P4, were studied through in-vitro experiments using RL95-2 cells. MAIN RESULTS
      AND THE ROLE OF CHANCE: AQP3 expression in the mid- and late-secretory phases of
      the human endometrium is significantly higher than in other phases. Since AQP3
      expression levels were higher in RL95-2 cells than in HEC-1A cells, mechanisms of
      AQP3 regulation by E2 and P4 were studied using RL95-2 cells. We provided the
      first report that P4 up-regulates AQP3 by directly targeting the promoter of the
      AQP3 gene. The up-regulation of AQP3 expression by a combination of E2 and P4 is
      significantly higher than that caused by either E2 or P4 alone. Together E2 and
      P4 promote RL95-2 cell migration and invasion by inducing EMT through AQP3. We
      also found that AQP3 co-localizes with ezrin and affects the formation of
      filopodia and lamellipodia during the E2 and P4-induced EMT process but has no
      effect on the expression of ezrin and F-actin. LARGE SCALE DATA: N/A.
      LIMITATIONS, REASONS FOR CAUTION: It is still unclear whether AQP3 is a main
      regulator of endometrial receptivity or one of several factors influencing the
      process. WIDER IMPLICATIONS OF THE FINDINGS: Further investigation on AQP3 may
      contribute to a greater understanding of endometrial receptivity. STUDY
      FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural
      Scientific Grants of China (No. 31570798), the Program for Liaoning Excellent
      Talents in University (LR2017042), the Doctoral Scientific Research Foundation of
      Liaoning province (201601236), and the Liaoning Provincial Program for Top
      Discipline of Basic Medical Sciences. There are no conflicts of interest.

PMID- 30285124
TI  - Carriage of the Toxic Shock Syndrome Toxin Gene by Contemporary Community
      Associated Staphylococcus aureus Isolates.
AB  - We report here the prevalence of the tst-1 gene among 252 methicillin-susceptible
      Staphylococcus aureus (MSSA) isolates and 458 methicillin-resistant S aureus
      (MRSA) isolates collected from 531 subjects between 2008 and 2017, one of which
      was recovered from a child with MRSA toxic shock syndrome. tst-1 was encoded by
      43 (6%) S aureus isolates overall: 42 (16.7%) MSSA isolates and 1 (0.2%) MRSA
      isolate (P < .001).

PMID- 30285125
TI  - Beta2-agonist induces net leg glucose uptake and free fatty acid release at rest
      but not during exercise in young men.
AB  - Objective: The role of selective beta2-adrenergic stimulation in regulation of
      leg glucose uptake and free fatty acid (FFA) balance is inadequately explored in
      humans. The objective of this study was to investigate beta2-adrenergic effects
      on net leg glucose uptake and clearance, and FFA balance at rest and during
      exercise. Design: The study was a randomized, placebo-controlled crossover trial,
      where 10 healthy men received either infusion of beta2-agonist terbutaline (0.2
      0.4 mg) or placebo. Net leg glucose uptake and clearance, and FFA balance were
      determined at rest and during 8 min of knee-extensor exercise using Fick's
      principle. Vastus lateralis muscle biopsies were collected at rest and at
      cessation of exercise. The primary outcome measure was net leg glucose uptake.
      Results: At rest, net leg glucose uptake and clearance were 0.35 (+/-0.16)
      mmol*min-1 and 41 (+/-17) mL*min-1 (mean+/-95%CI) higher (p<0.001) for
      terbutaline than placebo, corresponding to increases of 84 and 70%. During
      exercise, no treatment differences were observed in net leg glucose uptake,
      whereas clearance was 101 (+/-86) mL*min-1 lower (p<0.05) for terbutaline than
      placebo. At rest, terbutaline induced a net leg FFA release of 21 (+/-14)
      umol*min-1, being different from placebo (p=0.04). During exercise, net leg FFA
      uptake was not different between the treatments. Conclusions: These observations
      indicate that beta2-agonist alters net leg glucose uptake and clearance, as well
      as FFA balance in humans, which is associated with myocellular beta2-adrenergic
      and insulin-dependent signaling. Furthermore, the study shows that exercise
      confounds the beta2-adrenergic effect on net leg glucose uptake and FFA balance.

PMID- 30285126
TI  - Explaining mechanisms that influence smoke-free implementation at the local
      level: A realist review of smoking bans.
AB  - Introduction: While studies have been undertaken to understand the adoption of
      outdoor and indoor smoking bans, not much is known about why implementation of
      smoke-free (SF) environments differs at local levels. As most European countries
      remain at the level of indoor bans, we aim to translate existing evidence into
      practical recommendations on how to improve SF (outdoor) implementation within
      European municipalities. Methods: We applied six methodological steps of a
      realist review consistent with the RAMESES publication standards for realist
      syntheses. Literature search was conducted in PubMed/MEDLINE and Web of Science.
      In total, 3,829 references were screened, of which 43 were synthesized. Studies
      dating from 2004-2015 with rigor evidence of SF implementation at the local level
      were selected. Implementation outcomes were SF enforcement, monitoring, non
      smoking compliance, and public support in cities. Results: The explanatory
      realist framework links 4 innovation stages with 3 context-mechanism-outcome
      configurations (CMOs). We identified "triggering trust", "increasing priorities",
      and "limiting opposing interests" as underlying mechanisms, when (1)
      establishing, (2) developing, (3) contesting, and (4) implementing local smoking
      bans. The CMOs support practical recommendations, such as (a) providing
      authorities with local data when establishing and developing bans, (b) developing
      long-term strategies and implementing state-funded SF programs to prioritize
      sustained enforcement, and (c) limiting opposing interests through the use of the
      child protection frame. Conclusions: This is the first realist review on the
      implementation of SF enviroments at the local level. The process-oriented theory
      explains how and why CMOs determine SF development in cities and municipalities
      from planning until implementation. Implications: In 2015, only 16% of the
      world's population lived under the jurisdiction of comprehensive smoke-free (SF)
      laws. The findings of this realist review are useful to implement WHO goals of
      the Framework Convention on Tobacco Control (FCTC) and specifically SF
      environments at more local levels and to adjust them to specific contextual
      circumstances. This paper unpacks three mechanisms that could be triggered by SF
      strategies developed at local levels and that can result in improved policy
      implementation. Such evidence is needed to enhance SF strategies at the level of
      cities and municipalities and to achieve WHO Healthy Cities Network objectives.

PMID- 30285127
TI  - Ultrasound evaluation in follow-up of urate-lowering therapy in gout: the USEFUL
      study.
AB  - Objectives: We aimed to determine the ability of ultrasonography (US) to show
      disappearance of urate deposits in gouty patients requiring urate-lowering
      therapy (ULT). Methods: We performed a 6-month multicentre prospective study
      including patients with: proven gout; presence of US features of gout (tophus
      and/or double contour sign) at the knee and/or first metatarsophalangeal joints;
      and no current ULT. US evaluations were performed at baseline and at months 3 and
      6 (M3, M6) after starting ULT. Outcomes were: the change in US features of gout
      at M6 according to final (M6) serum urate (SU) level (high, > 360 MUmol/l, i.e. >
      6 mg/dl; low, 300-360 MUmol/l, i.e. 5-6 mg/dl; very low, < 300 MUmol/l, i.e. < 5
      mg/dl); and correlation between changed US features and final SU level. Results:
      We included 79 gouty patients (mean +/- s.d., age 61.8 (14) years, 91% males,
      disease duration 6.3 (6.1) years). Baseline SU level was 530 +/- 97 umol/l (i.e.
      8.9 mg/dl +/- 1.6mg/dl). At least one US tophus and double contour sign was
      observed in 74 (94%) and 68 (86%) patients, respectively. Among the 67 completers
      at M6, 18 and 39 achieved a very low and low SU level, respectively. We found a
      significant decrease in US features of gout among patients with the lowest SU
      level (P < 0.001). Final M6 SU level was positively correlated with decreased
      size of tophus (r = 0.54 [95% CI: 0.34, 0.70], P < 0.0001), and inversely
      correlated with proportion of double contour sign disappearance (r=-0.59 [-0.74, 
      0.40]). Conclusion: US can show decreased urate deposition after ULT, which is
      correlated with decreased SU level. The responsiveness of US in gout is
      demonstrated and can be useful for gout follow-up and adherence to ULT.

PMID- 30285128
TI  - Enhancing nutrient utilization of broiler chickens through supplemental enzymes.
AB  - The objective was to determine effects of adding phytase, amylase, and a cocktail
      of non-starch polysaccharide-degrading enzymes (NSPase) individually or in
      combinations to corn-soybean meal-based diet for broilers on apparent ileal
      digestibility (AID) of nutrients and dietary AMEn value. Four hundred and eighty
      male broiler chicks were divided into 80 groups and fed 8 diets in a completely
      randomized design (10 groups/diet) from day 15 to 21 of age. The diets were basal
      diet unsupplemented or supplemented with phytase (1,500 FTU/kg; Ronozyme HiPhos),
      amylase (80 KNU/kg, Ronozyme HiStarch), and NSPase (75 g/metric ton, Ronozyme
      Multigrain) individually or in all possible combinations. The basal diet
      contained the phytase at 1,000 FTU/kg, and was formulated to meet the NRC (1994)
      recommended nutrient requirements for broiler chickens except for ME, Ca, and non
      phytate P, which were reduced by 150 kcal/kg, 0.18%, and 0.15%, respectively.
      Addition of phytase to the basal diet increased (P < 0.05) AID of P from 40.4 to
      59.3%. Addition of amylase, NSPase or a combination of amylase and NSPase to the
      phytase-supplemented basal diet further increased (P < 0.05) AID of P to 63.4,
      69.9, and 67.3%, respectively. Addition of phytase, amylase or a combination of
      amylase and NSPase to the basal diet did not affect dietary AMEn value. However,
      addition of NSPase alone or a combination of phytase and amylase or of phytase
      and NSPase to the basal diet improved (P < 0.05) dietary AMEn value from 3,203 to
      3,339, 3,309 or 3,289 kcal/kg, respectively. In conclusion, it is more beneficial
      (with regard to AID of P and dietary AMEn) to add amylase and NSPase to phytase
      supplemented diets for broilers. Because the basal diet contained phytase at
      1,000 FTU/kg, the increase in AID of P due to supplemental phytase (1,500 FTU/kg)
      indicates that supplemental phytase at 2,500 FTU/kg is more beneficial with
      regard to improving AID of P than supplemental phytase at 1,000 FTU/kg.

PMID- 30285130
TI  - Hydrochlorothiazide and the Risk of Malignant Melanoma.

PMID- 30285132
TI  - Lactic Acidosis, Metformin Use, and Dose-Response Association.

PMID- 30285131
TI  - Reduced Opioid Marketing Could Limit Prescribing Information for Physicians.

PMID- 30285133
TI  - Lactic Acidosis, Metformin Use, and Dose-Response Association.

PMID- 30285134
TI  - Lactic Acidosis, Metformin Use, and Dose-Response Association.

PMID- 30285136
TI  - Association of Increased Attending Physician Supervision With Patient Safety and
      Educational Outcomes.

PMID- 30285135
TI  - The Patient Experience and Use of Telemetry Monitoring.

PMID- 30285137
TI  - Psychotherapeutics for Chronic Pain Extends Beyond Cognitive Behavioral Therapy.

PMID- 30285138
TI  - Hydrochlorothiazide and the Risk of Malignant Melanoma-Reply.

PMID- 30285139
TI  - Reduced Opioid Marketing Could Limit Prescribing Information for Physicians
      Reply.

PMID- 30285140
TI  - Lactic Acidosis, Metformin Use, and Dose-Response Association-Reply.

PMID- 30285141
TI  - The Patient Experience and Use of Telemetry Monitoring-Reply.

PMID- 30285142
TI  - Association of Increased Attending Physician Supervision With Patient Safety and
      Educational Outcomes-Reply.

PMID- 30285143
TI  - Psychotherapeutics for Chronic Pain Extends Beyond Cognitive Behavioral Therapy
      Reply.

PMID- 30285145
TI  - The Influence of Health Numeracy and Health Warning Label Type on Smoking Myths
      and Quit-Related Reactions.
AB  - Introduction: Health numeracy helps individuals understand risk information, but
      limited data exist concerning numeracy's role in reactions to varying types of
      health warning labels (HWLs) for cigarettes. Methods: A nationally representative
      online panel of adult current smokers received two exposures (1 week apart) to
      nine HWLs with either text-only or pictorial images with identical mandated text.
      Following the second exposure, participants (n = 594) rated their beliefs in
      smoking myths (eg, health-promoting behaviors can undo the risks of smoking) and
      how much the warnings made them want to quit smoking. Generalized estimating
      equation regression examined the relation of objective health numeracy and its
      interaction with HWL type to smoking-myth beliefs and quit-related reactions.
      Results: Health numeracy was not significantly associated with smoking-myth
      beliefs; the interaction with HWL type was also nonsignificant. Adult smokers
      with lower health numeracy had higher quit-related reactions than those with
      higher numeracy following exposure to HWLs. The type of HWL significantly
      modified numeracy's associations with quit-related reactions; no significant
      association existed between text-only HWLs and quit-related reactions, whereas
      among those who viewed the pictorial warnings, lower numeracy was associated with
      greater quit-related reactions (beta = -.23; p < .001). Conclusions: Lower as
      compared to higher health numeracy was significantly associated with higher quit
      related reactions to HWLs and especially with pictorial HWLs. Health numeracy and
      HWL type were not associated with the endorsement of smoking myths. The role of
      health numeracy in effectively communicating risks to smokers warrants thoughtful
      consideration in the development of tobacco HWLs. Implications: Health numeracy
      plays an important role in an individual's ability to understand and respond to
      health risks. Smokers with lower health numeracy had greater quit-related
      reactions to pictorial health warnings than those who viewed text-only warning
      labels. Development and testing of health warning labels should consider health
      numeracy to most effectively communicate risk to US smokers.

PMID- 30285146
TI  - Leptin as a breast milk component for the prevention of obesity.
AB  - Leptin ingested as a component of breast milk is increasingly recognized to play
      a role in the postnatal programming of a healthy phenotype in adulthood. Besides
      its primary function in controlling body weight, leptin may be an essential
      nutrient required during lactation to ensure that the system controlling fat
      accumulation and body composition is well organized from the early stages of
      development. This review delves into the following topics: (1) the imprinted
      protective function of adequate leptin intake during lactation in future
      metabolic health; (2) the consequences of a lack of leptin intake or of
      alterations in leptin levels; and (3) the mechanisms described for the effects of
      leptin on postnatal programming. Furthermore, it highlights the importance of
      breastfeeding and the need to establish optimal or reference intake values for
      leptin during lactation to design patterns of personalized nutrition from early
      childhood.

PMID- 30285147
TI  - Infant nocturnal wakefulness: a longitudinal study comparing three sleep
      assessment methods.
AB  - Study Objectives: To examine the convergence between actigraphy, sleep diaries,
      and the Brief Infant Sleep Questionnaire (BISQ) in the assessment of infant
      nocturnal wakefulness (i.e. minutes awake after sleep onset [WASO] and number of
      night-wakings [NW]) in the context of a longitudinal study. Methods: The sample
      included 226 families, who were recruited during pregnancy. Data were collected
      at 3, 6, 12, and 18 months postpartum. Infants' sleep was monitored at home for
      five nights using actigraphy, sleep diaries, and the BISQ. Outcome measures
      included WASO and NW, as well as sleep latency, sleep duration, and sleep onset.
      Results: Trajectory analyses demonstrated that all three methods showed declines
      in NW and WASO from 3 to 18 months. Statistically significant correlations were
      found between the three methods at all assessment points for all sleep variables.
      However, agreement rates (using Krippendorff's alpha and Bland-Altman analyses)
      between actigraphy and parental reports were poor. For NW, agreement between
      actigraphy and parental reports at 18 months was lower than that at 3 and 6
      months. Diaries and BISQ showed satisfactory agreement for sleep latency.
      Conclusions: Although the three methods' measures of infant nocturnal wakefulness
      are significantly correlated during infancy, absolute agreement between these
      methods is poor overall. The growing disagreement between actigraphy and parental
      reports (in NW) across development probably suggests that parents become less
      aware of infants' awakenings, due to the increasing ability of infants to self
      soothe. Using both objective and subjective assessment methods seems especially
      important after the age of 6 months.

PMID- 30285148
TI  - Effect of embryonic thermal manipulation on heat shock protein 70 (HSP70)
      expression and subsequent immune response to post-hatch lipopolysaccharide
      challenge in Pekin ducklings.
AB  - During the course of multi-stage incubation, small locational differences in
      incubation temperature within a machine are not uncommon and so the goal of this
      study was to study the immune response of ducklings exposed to thermal
      manipulation during incubation. Commercial Pekin duck eggs (n = 200) were
      distributed among four treatment: SS-Control (37.5 degrees C from embryonic day
      [ED] 1 to 25); SS-LPS (37.5 degrees C from ED1 to 25 + LPS at D0 [hatch]); HH-LPS
      (38 degrees C from ED1 to 25+ LPS at D0); SH-LPS (37.5 degrees C from ED1 to 10
      and 38 degrees C from ED 11 to 25 + LPS at D0). At D0, ducklings received a
      lipopolysaccharide (LPS) injection. At D1 and D5, the HH-LPS treatment
      significantly reduced body weight (P <= 0.05). At D1 and D3 post-LPS injection,
      the SH-LPS and HH-LPS treatments significantly reduced splenic and bursal heat
      shock protein 70 (HSP70), mRNA abundance, and macrophage nitric oxide production
      compared with the SS-LPS treatment (P <= 0.05). At D1, the HH-LPS and SH-LPS
      treatments had increased splenic IL-10 mRNA and lower MHC I mRNA compared with
      the SS-LPS treatment (P <= 0.05). At D1, the HH-LPS treatment increased splenic
      IL-6 mRNA and bursal IFNgamma mRNA transcription while the SH-LPS treatment
      reduced splenic IL-6 mRNA compared with the SS-LPS treatment (P <= 0.05). The HH
      LPS treatment reduced thymocyte proliferation efficiency, while at D1, D3, and
      D5, the SH-LPS treatment increased thymocyte proliferation efficiency compared
      with the SS-LPS treatment (P <= 0.05). Ducklings in the HH-LPS treatment had a
      higher splenic CD8+/CD4+ ratio compared to the SS-LPS treatment at D3 post-LPS
      injection (P <= 0.05). In summary, the HH-LPS treatment compromised
      immunocompetence via decreased NO production and thymocyte proliferation
      efficiency, while the SH-LPS treatment increased body weight and thymocyte
      proliferation and reduced IL-6 mRNA abundance. This suggests that an embryonic
      temperature stress during the latter half of incubation may prime the immune
      system which may be beneficial during secondary post-hatch inflammatory
      challenges.

PMID- 30285149
TI  - Evolution of intestinal microbiota and body compartments during spontaneous
      hyperphagia in the Greylag goose.
AB  - The aim of this work was to study the effects of spontaneous hyperphagia on the
      evolution of intestinal microbiota and body compartments in old goose. From
      October 25th to November 26th, 5-yr-old breeding Greylag Landaise geese (106
      males and 106 females) were fed with grass during 1 mo (G period). From November
      26th (0 d) the birds had ad libitum access to pellets (AMEn: 10.5 MJ/kg, CP: 18.9
      g/kg; spontaneous fattening (SF) period). Some birds were killed at -31 d (n =
      24; 50/50 sex ratio), 0 d (n = 48), 14 (n = 46), 22 d (n = 46), and 70 d (n = 48)
      after the start of G period to measure body traits. For microbial analysis, 10 of
      the samples per sex at 0 d, 14 d, and 70 d were selected to be representative of
      body traits. Between 0 and 22 d, liver weight increased from 98 g to 194 g in
      males and from 89 g to 199 g in females (P < 0.001). Liver weight decreased
      between 22 and 70 d from 194 to 174 g in males and from 199 to 163 g in females
      (P < 0.001). Irrespective of the diet (G or SF period) and the sex of the bird,
      the two major phyla were Proteobacteria (49%) and Firmicutes (48%). Bacteroidetes
      represented around 3.0% of the sequences. At order level, Firmicutes were
      dominated by Clostridiales (33% of total sequences) and Lactobacillales (13% of
      total sequences) and Proteobacteria were dominated by Campylobacteriales (34% of
      total sequences). Finally, Bacteroidetes were dominated by Bacteroidales. SF and
      sex did not change the microbial diversity but sparse partial least squares
      discriminant analysis allowed us to highlight discriminant operational taxonomic
      unit between experimental groups. In conclusion, our result showed that changes
      in the body compartments of old geese during spontaneous hyperphagia depend on
      the sex of the birds, but not so much in gut microbial composition. Further
      investigations are necessary to understand the functional microbiota and
      highlight the role of gut microbiota in hepatic steatosis induced with
      hyperphagia in geese.

PMID- 30285151
TI  - Feasibility of a smartphone-based tobacco treatment for HIV-infected smokers.
AB  - Background: Cigarette smoking is common among persons living with HIV (PLWH) in
      the US, it is the leading cause of mortality in this group, and efforts to
      promote cessation have been largely unsuccessful. Methods: From 2015-2017, we
      performed a randomized controlled trial of Positively Smoke Free- Mobile (PSF-M)
      vs. standard care. PSF-M is a mobile website that offers a 42-day text message
      based quit-smoking program with smartphone features including quit-day
      selection/calendar, educational/motivational videos, and HELP button for
      cravings. Results: One hundred individuals enrolled, 48 were randomized to PSF-M
      (mean age=45, 54% male, 81% Black, 31% Latino) and 52 to the standard care
      condition. All participants were offered a three month supply of nicotine
      patches. Participants randomized to the mobile intervention visited the PSF-M
      homepage a mean of 83 times, viewed 5.6/8 videos, logged in on 13 of 42 possible
      days, and received 131 texts. 77% tapped HELP for cravings, and craving response
      options were utilized by the following proportions: phone-a-friend-58%, play-a
      game-29%, play-a-song-4%. Older age and non-Black race were both associated with
      higher levels of engagement with the site. 61% rated PSF-M very/extremely
      helpful, and 98% would recommend PSF-M to PLWH family/friends. Abstinence at 3
      months, quit attempts, and daily cigarette intake all favored PSF-M over standard
      care, but did not achieve statistical significance in our pilot sample.
      Conclusions: Smartphone-based tobacco treatment for PLWH was feasible and
      achieved moderate-high rates of engagement and satisfaction in a middle-aged,
      ethnic/racial minority group in the poorest urban community in the US.
      Implications: Cigarette smoking has emerged as the leading killer of persons
      living with HIV (PLWH). Behavioral interventions have achieved only limited
      success in promoting cessation in this population. In the current study we
      explore the feasibility and preliminary efficacy of a multimodal, web-based, quit
      smoking intervention delivered to PLWH smokers via their smartphones.

PMID- 30285150
TI  - Effect of Hidden Relatedness on Single-Step Genetic Evaluation in an Advanced
      Open-Pollinated Breeding Program.
AB  - Open-pollinated (OP) mating is frequently used in forest tree breeding due to the
      relative temporal and financial efficiency of the approach. The trade-off is the
      lower precision of the estimated genetic parameters. Pedigree/sib-ship
      reconstruction has been proven as a tool to correct and complete pedigree
      information and to improve the precision of genetic parameter estimates. Our
      study analyzed an advanced generation Eucalyptus population from an OP breeding
      program using single-step genetic evaluation. The relationship matrix inferred
      from sib-ship reconstruction was used to rescale the marker-based relationship
      matrix (G matrix). This was compared with a second scenario that used rescaling
      based on the documented pedigree. The proposed single-step model performed better
      with respect to both model fit and the theoretical accuracy of breeding values.
      We found that the prediction accuracy was superior when using the pedigree
      information only when compared with using a combination of the pedigree and
      genomic information. This pattern appeared to be mainly a result of accumulated
      unrecognized relatedness over several breeding cycles, resulting in breeding
      values being shrunk toward the population mean. Using biased, pedigree-based
      breeding values as the base with which to correlate predicted GEBVs, resulted in
      the underestimation of prediction accuracies. Using breeding values estimated on
      the basis of sib-ship reconstruction resulted in increased prediction accuracies
      of the genotyped individuals. Therefore, selection of the correct base for
      estimation of prediction accuracy is critical. The beneficial impact of sib-ship
      reconstruction using G matrix rescaling was profound, especially in traits with
      inbreeding depression, such as stem diameter.

PMID- 30285152
TI  - Bacillus amyloliquefaciens spray improves the growth performance, immune status,
      and respiratory mucosal barrier in broiler chickens.
AB  - Studies have shown that supplementing probiotics in a nasal spray can provide
      prophylaxis against upper respiratory tract infections. Previously, we found that
      spraying with Bacillus reduced the concentration of atmospheric ammonia and
      airborne microbiological aerosols in broiler houses. In the present study, we
      evaluated the effects of spraying with Bacillus amyloliquefaciens on the
      respiratory mucosal barrier in broilers. Two trails were conducted simultaneously
      in four environmentally controlled chambers. In each trail, 320 1-d-old male
      broilers were randomly assigned to control (CON) and B. amyloliquefaciens (BAQ)
      group. Eight cages containing 20 birds per cage were placed in two chambers. The
      BAQ group chambers were sprayed with B. amyloliquefaciens at 4 * 109 CFU/m2 each
      day for 42 d. Spraying with B. amyloliquefaciens increased average daily gain and
      average daily feed intake in broilers (P < 0.01), but had no effects on FCR (P >
      0.05). The relative weights of the bursa (21 d) and spleen (42 d) were higher in
      the BAQ group (P < 0.05). The serum IgG, IgM (21 d), and IgA, Ig M (42 d) levels
      were improved in BAQ group (P < 0.05). The sIgA levels in tracheal lavage fluid
      were significantly higher in the BAQ group than the CON group (P < 0.05).
      Furthermore, treatment with BAQ downregulated IL-6 and IFN-gamma (P < 0.05), but
      upregulated IL-2, occludin, and mucin-2 (P < 0.05). In addition, the number of
      acidic goblet cells was significantly higher in the tracheas of treated broilers
      than untreated broilers (P < 0.05). In conclusion, spraying with B.
      amyloliquefaciens may help to enhance the growth performance and improve the
      respiratory mucosal barrier in broiler chickens.

PMID- 30285155
TI  - Endoplasmic reticulum stress affected chondrocyte apoptosis in femoral head
      necrosis induced by glucocorticoid in broilers.
AB  - In our previous study, chondrocyte apoptosis in femoral head necrosis (FHN)
      affected broilers was found to be associated with the endoplasmic reticulum
      stress (ERS) signaling pathway. In the present study, we further explored the
      role of ERS-induced chondrocyte apoptosis in FHN-affected broilers and the
      parallel test was carried out with articular chondrocytes cultivated in vitro.
      The broilers and chondrocytes were treated with methylprednisolone (MP). The main
      pathological changes in FHN-affected broilers included the proximal femoral head
      separated from its articular cartilage and growth plate lesions. MP-treated
      chondrocytes demonstrated morphology changes, cell viability reduction, secretory
      capacity dysfunction, and apoptosis. The mRNA expressions of pro-apoptotic genes
      controlled by ERS signaling pathway were up-regulated both in vivo and in vitro
      experiments. It showed that MP induced FHN in broilers, activated apoptosis
      related genes on ERS signaling pathway, and affected the survival and apoptosis
      of chondrocytes, and bone growth.

PMID- 30285153
TI  - Nonfilament-forming RecA dimer catalyzes homologous joint formation.
AB  - Homologous recombination is essential to genome maintenance, and also to genome
      diversification. In virtually all organisms, homologous recombination depends on
      the RecA/Rad51-family recombinases, which catalyze ATP-dependent formation of
      homologous joints-critical intermediates in homologous recombination. RecA/Rad51
      binds first to single-stranded (ss) DNA at a damaged site to form a spiral
      nucleoprotein filament, after which double-stranded (ds) DNA interacts with the
      filament to search for sequence homology and to form consecutive base pairs with
      ssDNA ('pairing'). How sequence homology is recognized and what exact role
      filament formation plays remain unknown. We addressed the question of whether
      filament formation is a prerequisite for homologous joint formation. To this end
      we constructed a nonpolymerizing (np) head-to-tail-fused RecA dimer (npRecA
      dimer) and an npRecA monomer. The npRecA dimer bound to ssDNA, but did not form
      continuous filaments upon binding to DNA; it formed beads-on-string structures
      exclusively. Although its efficiency was lower, the npRecA dimer catalyzed the
      formation of D-loops (a type of homologous joint), whereas the npRecA monomer was
      completely defective. Thus, filament formation contributes to efficiency, but is
      not essential to sequence-homology recognition and pairing, for which a head-to
      tail dimer form of RecA protomer is required and sufficient.

PMID- 30285156
TI  - Effects of caponization and age on the histology, lipid localization, and fiber
      diameter in muscles from Leghorn cockerels.
AB  - Poultry researchers seek general and native lines of birds for capon production.
      The primary aim is to find high-quality meat with valuable sensory attributes.
      Castration decreases androgen levels and changes lipid metabolism, resulting in
      the accumulation of abdominal, subcutaneous, and intramuscular fat, which changes
      the flavor, texture, and tenderness of the meat. Histological analysis of
      selected skeletal muscles from Leghorn capons and cockerels was the main aim of
      the present study, along with examination of lipid localization in muscle tissue.
      We also assessed fiber type and diameter in the pectoral muscles (pectoralis
      major). The experiment was performed on 200 Leghorn cockerels; testes were
      removed at 8 wk of age. At 12, 16, 20, 24, and 28 wk of age, 6 cockerels and 6
      capons were slaughtered, and samples from the pectoral and thigh muscles were
      evaluated. Differences in the focal necrosis of the fibers with infiltration of
      lymphoid cells (P < 0.05) were observed in thigh muscles, with higher numbers in
      cockerels than in capons. All examined locations in the pectoral and thigh
      muscles of capons (around the blood vessels, in the perimysium, in the
      endomysium, and in the sarcoplasm) showed higher concentrations of lipids
      compared to levels in cockerels. The analysis of fiber type in pectoralis major
      muscles revealed that all fibers were type IIB. The diameters of the fibers of
      the pectoral muscles were different (P < 0.05) at 28 wk of age, and the diameters
      of the giant fibers were different (P < 0.05) at 16 wk of age. The high
      concentration of lipids in the skeletal muscles of Leghorn capons is remarkable.
      Thus, ethical reasons as well as economic reasons should be considered when one
      day-old cockerels are eliminated.

PMID- 30285154
TI  - Why are Hoogsteen base pairs energetically disfavored in A-RNA compared to B-DNA?
AB  - A(syn)-U/T and G(syn)-C+ Hoogsteen (HG) base pairs (bps) are energetically more
      disfavored relative to Watson-Crick (WC) bps in A-RNA as compared to B-DNA by >1
      kcal/mol for reasons that are not fully understood. Here, we used NMR
      spectroscopy, optical melting experiments, molecular dynamics simulations and
      modified nucleotides to identify factors that contribute to this destabilization
      of HG bps in A-RNA. Removing the 2'-hydroxyl at single purine nucleotides in A
      RNA duplexes did not stabilize HG bps relative to WC. In contrast, loosening the
      A-form geometry using a bulge in A-RNA reduced the energy cost of forming HG bps
      at the flanking sites to B-DNA levels. A structural and thermodynamic analysis of
      purine-purine HG mismatches reveals that compared to B-DNA, the A-form geometry
      disfavors syn purines by 1.5-4 kcal/mol due to sugar-backbone rearrangements
      needed to sterically accommodate the syn base. Based on MD simulations, an
      additional penalty of 3-4 kcal/mol applies for purine-pyrimidine HG bps due to
      the higher energetic cost associated with moving the bases to form hydrogen bonds
      in A-RNA versus B-DNA. These results provide insights into a fundamental
      difference between A-RNA and B-DNA duplexes with important implications for how
      they respond to damage and post-transcriptional modifications.

PMID- 30285158
TI  - Incorrect Data or Information.

PMID- 30285157
TI  - Gut Microbes May Account for the Anti-Seizure Effects of the Ketogenic Diet.

PMID- 30285159
TI  - Incorrect Units.

PMID- 30285161
TI  - Rare Infection Linked With SGLT-2 Inhibitor Use.

PMID- 30285160
TI  - Physical Therapy or Arthroscopic Surgery for Treatment of Meniscal Tears: Is
      Noninferiority Enough?

PMID- 30285162
TI  - Tretinoin in New Lotion Formula.

PMID- 30285163
TI  - New Drug Treats Rare, Debilitating Neurotrophic Keratitis.

PMID- 30285165
TI  - Given Their Potential for Harm, It's Time to Focus on the Safety of Supplements.

PMID- 30285166
TI  - The Book Forum.

PMID- 30285167
TI  - Electronic Cigarette Sales in the United States, 2013-2017.

PMID- 30285168
TI  - Presence of High-Intensity Sweeteners in Popular Cigarillos of Varying Flavor
      Profiles.

PMID- 30285169
TI  - Glyburide vs Insulin for Gestational Diabetes.

PMID- 30285170
TI  - Acupuncture for Women Undergoing In Vitro Fertilization.

PMID- 30285171
TI  - Acupuncture for Women Undergoing In Vitro Fertilization.

PMID- 30285172
TI  - Factors Associated With Variation in Outcomes in Bariatric Surgery Centers of
      Excellence.

PMID- 30285173
TI  - Glyburide vs Insulin for Gestational Diabetes-Reply.

PMID- 30285174
TI  - Acupuncture for Women Undergoing In Vitro Fertilization-Reply.

PMID- 30285175
TI  - Factors Associated With Variation in Outcomes in Bariatric Surgery Centers of
      Excellence-Reply.

PMID- 30285176
TI  - Ciprofloxacin Otic Suspension (Otiprio) for Acute Otitis Externa.

PMID- 30285177
TI  - Effect of Early Surgery vs Physical Therapy on Knee Function Among Patients With
      Nonobstructive Meniscal Tears: The ESCAPE Randomized Clinical Trial.
AB  - Importance: Despite recent studies suggesting arthroscopic partial meniscectomy
      (APM) is not more effective than physical therapy (PT), the procedure is still
      frequently performed in patients with meniscal tears. Objective: To assess
      whether PT is noninferior to APM for improving patient-reported knee function in
      patients with meniscal tears. Design, Setting, and Participants: Noninferiority,
      multicenter, randomized clinical trial conducted in 9 hospitals in the
      Netherlands. Participants were aged 45 to 70 years with nonobstructive meniscal
      tears (ie, no locking of the knee joint). Patients with knee instability, severe
      osteoarthritis, and body mass index greater than 35 were excluded. Recruitment
      took place between July 17, 2013, and November 4, 2015. Participants were
      followed up for 24 months (final participant follow-up, October 11, 2017).
      Interventions: Three hundred twenty-one participants were randomly assigned to
      APM (n = 159) or a predefined PT protocol (n = 162). The PT protocol consisted of
      16 sessions of exercise therapy over 8 weeks focused on coordination and closed
      kinetic chain strength exercises. Main Outcomes and Measures: The primary outcome
      was change in patient-reported knee function on the International Knee
      Documentation Committee Subjective Knee Form (range, 0 to 100; from worse to
      best) from baseline over a 24-month follow-up period. The noninferiority margin
      was defined as a difference between treatment groups of 8 points and was assessed
      with a 1-sided alpha of .025. The primary analysis followed the intention-to
      treat principle. Results: Among 321 patients who were randomized (mean [SD] age,
      58 [6.6] years; 161 women [50%]), 289 (90%) completed the trial (161 women and
      158 men). In the PT group, 47 participants (29%) had APM during the 24-month
      follow-up period, and 8 participants randomized to APM (5%) did not have APM.
      Over a 24-month follow-up period, knee function improved in the APM group by 26.2
      points (from 44.8 to 71.5) and in the PT group by 20.4 points (from 46.5 to
      67.7). The overall between-group difference was 3.6 points (97.5% CI, -infinity
      to 6.5; P value for noninferiority = .001). Adverse events occurred in 18
      participants in the APM group and 12 in the PT group. Repeat surgery (3 in the
      APM group and 1 in the PT group) and additional outpatient visits for knee pain
      (6 in the APM group and 2 in the PT group) were the most frequent adverse events.
      Conclusions and Relevance: Among patients with nonobstructive meniscal tears, PT
      was noninferior to APM for improving patient-reported knee function over a 24
      month follow-up period. Based on these results, PT may be considered an
      alternative to surgery for patients with nonobstructive meniscal tears. Trial
      Registration: ClinicalTrials.gov Identifier: NCT01850719.

PMID- 30285178
TI  - Association of Clinical and Social Factors With Excess Hypertension Risk in Black
      Compared With White US Adults.
AB  - Importance: The high prevalence of hypertension among the US black population is
      a major contributor to disparities in life expectancy; however, the causes for
      higher incidence of hypertension among black adults are unknown. Objective: To
      evaluate potential factors associated with higher risk of incident hypertension
      among black adults. Design, Setting, and Participants: Prospective cohort study
      of black and white adults selected from a longitudinal cohort study of 30 239
      participants as not having hypertension at baseline (2003-2007) and participating
      in a follow-up visit 9.4 years (median) later. Exposures: There were 12 clinical
      and social factors, including score for the Southern diet (range, -4.5 to 8.2;
      higher values reflect higher level of adherence to the dietary pattern),
      including higher fried and related food intake. Main Outcomes and Measures:
      Incident hypertension (systolic blood pressure >=140 mm Hg, diastolic blood
      pressure >=90 mm Hg, or use of antihypertensive medications) at the follow-up
      visit. Results: Of 6897 participants (mean [SD] age, 62 [8] years; 26% were black
      adults; and 55% were women), 46% of black participants and 33% of white
      participants developed hypertension. Black men had an adjusted mean Southern diet
      score of 0.81 (95% CI, 0.72 to 0.90); white men, -0.26 (95% CI, -0.31 to -0.21);
      black women, 0.27 (95% CI, 0.20 to 0.33); and white women, -0.57 (95% CI, -0.61
      to -0.54). The Southern diet score was significantly associated with incident
      hypertension for men (odds ratio [OR], 1.16 per 1 SD [95% CI, 1.06 to 1.27];
      incidence of 32.4% at the 25th percentile and 36.1% at the 75th percentile;
      difference, 3.7% [95% CI, 1.4% to 6.2%]) and women (OR, 1.17 per 1 SD [95% CI,
      1.08 to 1.28]; incidence of 31.0% at the 25th percentile and 34.8% at the 75th
      percentile; difference, 3.8% [95% CI, 1.5% to 5.8%]). The Southern dietary
      pattern was the largest mediating factor for differences in the incidence of
      hypertension, accounting for 51.6% (95% CI, 18.8% to 84.4%) of the excess risk
      among black men and 29.2% (95% CI, 13.4% to 44.9%) of the excess risk among black
      women. Among black men, a higher dietary ratio of sodium to potassium and an
      education level of high school graduate or less each mediated 12.3% of the excess
      risk of incident hypertension. Among black women, higher body mass index mediated
      18.3% of the excess risk; a larger waist, 15.2%; less adherence to the Dietary
      Approaches to Stop Hypertension diet, 11.2%; income level of $35 000 or less,
      9.3%; higher dietary ratio of sodium to potassium, 6.8%; and an education level
      of high school graduate or less, 4.1%. Conclusions and Relevance: In a mediation
      analysis comparing incident hypertension among black adults vs white adults in
      the United States, key factors statistically mediating the racial difference for
      both men and women included Southern diet score, dietary ratio of sodium to
      potassium, and education level. Among women, waist circumference and body mass
      index also were key factors.

PMID- 30285182
TI  - Nurturing Medicine.

PMID- 30285180
TI  - Tinea Versicolor.

PMID- 30285183
TI  - Diagnosis and Management of Rheumatoid Arthritis: A Review.
AB  - Importance: Rheumatoid arthritis (RA) occurs in about 5 per 1000 people and can
      lead to severe joint damage and disability. Significant progress has been made
      over the past 2 decades regarding understanding of disease pathophysiology,
      optimal outcome measures, and effective treatment strategies, including the
      recognition of the importance of diagnosing and treating RA early. Observations:
      Early diagnosis and treatment of RA can avert or substantially slow progression
      of joint damage in up to 90% of patients, thereby preventing irreversible
      disability. The development of novel instruments to measure disease activity and
      identify the presence or absence of remission have facilitated new treatment
      strategies to arrest RA before joints are damaged irreversibly. Outcomes have
      been improved by recognizing the benefits of early diagnosis and early therapy
      with disease-modifying antirheumatic drugs (DMARDs). The treatment target is
      remission or a state of at least low disease activity, which should be attained
      within 6 months. Methotrexate is first-line therapy and should be prescribed at
      an optimal dose of 25 mg weekly and in combination with glucocorticoids; 40% to
      50% of patients reach remission or at least low disease activity with this
      regimen. If this treatment fails, sequential application of targeted therapies,
      such as biologic agents (eg, tumor necrosis factor [TNF] inhibitors) or Janus
      kinase inhibitors in combination with methotrexate, have allowed up to 75% of
      these patients to reach the treatment target over time. New therapies have been
      developed in response to new pathogenetic findings. The costs of some therapies
      are considerable, but these costs are decreasing with the advent of biosimilar
      drugs (drugs essentially identical to the original biologic drugs but usually
      available at lower cost). Conclusions and Relevance: Scientific advances have
      improved therapies that prevent progression of irreversible joint damage in up to
      90% of patients with RA. Early treatment with methotrexate plus glucocorticoids
      and subsequently with other DMARDs, such as inhibitors of TNF, IL-6, or Janus
      kinases, improves outcomes and prevents RA-related disability. A treat-to-target
      strategy aimed at reducing disease activity by at least 50% within 3 months and
      achieving remission or low disease activity within 6 months, with sequential drug
      treatment if needed, can prevent RA-related disability.

PMID- 30285179
TI  - Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related
      Symptoms in Patients With Subclinical Hypothyroidism: A Systematic Review and
      Meta-analysis.
AB  - Importance: The benefit of thyroid hormone therapy for subclinical hypothyroidism
      is uncertain. New evidence from recent large randomized clinical trials warrants
      an update of previous meta-analyses. Objective: To conduct a meta-analysis of the
      association of thyroid hormone therapy with quality of life and thyroid-related
      symptoms in adults with subclinical hypothyroidism. Data Sources: PubMed, EMBASE,
      ClinicalTrials.gov, Web of Science, Cochrane Library, CENTRAL, Emcare, and
      Academic Search Premier from inception until July 4, 2018. Study Selection:
      Randomized clinical trials that compared thyroid hormone therapy with placebo or
      no therapy in nonpregnant adults with subclinical hypothyroidism were eligible.
      Two reviewers independently evaluated eligibility based on titles and abstracts
      of all retrieved studies. Studies not excluded in this first step were
      independently assessed for inclusion after full-text evaluation by 2 reviewers.
      Data Extraction and Synthesis: Two independent reviewers extracted data, assessed
      risk of bias (Cochrane risk-of-bias tool), and evaluated the quality of evidence
      (GRADE tool). For synthesis, differences in clinical scores were transformed (eg,
      quality of life) into standardized mean differences (SMDs; positive values
      indicate benefit of thyroid hormone therapy; 0.2, 0.5, and 0.8 correspond to
      small, moderate, and large effects, respectively). Random-effects models for meta
      analyses were applied. Main Outcomes and Measures: General quality of life and
      thyroid-related symptoms after a minimum follow-up of 3 months. Results: Overall,
      21 of 3088 initially identified publications met the inclusion criteria, with
      2192 adults randomized. After treatment (range, 3-18 months), thyroid hormone
      therapy was associated with lowering the mean thyrotropin value into the normal
      reference range compared with placebo (range, 0.5-3.7 mIU/L vs 4.6 to 14.7 mIU/L)
      but was not associated with benefit regarding general quality of life (n = 796;
      SMD, -0.11; 95% CI, -0.25 to 0.03; I2=66.7%) or thyroid-related symptoms (n =
      858; SMD, 0.01; 95% CI, -0.12 to 0.14; I2=0.0%). Overall, risk of bias was low
      and the quality of evidence assessed with the GRADE tool was judged moderate to
      high. Conclusions and Relevance: Among nonpregnant adults with subclinical
      hypothyroidism, the use of thyroid hormone therapy was not associated with
      improvements in general quality of life or thyroid-related symptoms. These
      findings do not support the routine use of thyroid hormone therapy in adults with
      subclinical hypothyroidism.

PMID- 30285186
TI  - Brief report of a tablet-delivered psychosocial intervention for men with
      advanced prostate cancer: Acceptability and efficacy by race.
AB  - Relative to non-Hispanic whites (NHW), black men are disproportionately affected
      by prostate cancer (PC) incidence, have poorer PC outcomes, and report greater
      compromises in health-related quality of life. Despite these challenges, black
      men are underrepresented in psychosocial cancer research, possibly due to limited
      access to supportive oncology programs. The purpose of this article is to examine
      the acceptability and efficacy for reducing disease-specific distress of a tablet
      delivered psychosocial intervention for older men with advanced PC (APC) and
      explore differences by race. Men with APC (N = 192, 37.5% black, age M = 68.84
      years) were randomized to 10-week Cognitive Behavioral Stress Management (CBSM)
      or attention-control Health Promotion (HP), both delivered via tablets.
      Assessments occurred at baseline in person, weekly during the 10-week program via
      tablets, and at 6 and 12 months in person. Weekly session evaluations and
      postprogram exit surveys assessed acceptability. Efficacy was assessed with a
      measure of PC-anxiety validated with racially diverse PC patients using linear
      mixed effects modeling. Study retention and group attendance did not differ by
      race. CBSM and HP were both acceptable among older APC patients. Black men rated
      both conditions more favorably than NHW men. Men in CBSM (vs. HP) reported
      greater reductions in PC-anxiety at 6 months (not sustained at 12 months). Black
      men in CBSM reported greater decreases in PC-anxiety over time compared with all
      other groups. Tablet-delivered CBSM and HP were acceptable for black and NHW APC
      patients, although black men rated both conditions more favorably. Black men
      reported a unique intervention benefit related to reduced disease-specific
      distress.

PMID- 30285187
TI  - Effects of dietary supplementation with Clostridium butyricum on laying
      performance, egg quality, serum parameters, and cecal microflora of laying hens
      in the late phase of production.
AB  - This experiment was conducted to evaluate the effects of dietary supplementation
      with Clostridium butyricum on laying performance, egg quality, serum parameters,
      and cecal microflora of laying hens in the late phase of production. Jinghong-1
      strain laying hens (n = 960; 48 wk of age) were randomly allocated to 5 treatment
      groups with 6 replicates of 32 hens. Hens were fed with basal diet (control) and
      basal diet supplemented with 2.5 * 104 (CB1), 5 * 104 (CB2), 1 * 105 (CB3), and 2
      * 105 (CB4) cfu/g C. butyricum for 10 wk. The results showed that egg production,
      egg mass, and eggshell strength increased quadratically as supplemental C.
      butyricum increased, and these responses were maximized in the CB2 group (P <
      0.05). Compared with the control group, the addition of C. butyricum resulted in
      quadratic effects on serum total protein, uric acid, calcium, complement
      component C3 and catalase concentrations, and these responses were maximized or
      minimized in the CB2 group (P < 0.05). Linear and quadratic increases were
      observed in serum IgM, total superoxide dismutase, and glutathione peroxidase
      concentrations, and these responses were maximized in CB2 or CB3 group (P <
      0.05). The addition of C. butyricum in the CB2 group resulted in linearly
      increasing levels of serum IgG concentration as compared with the control group
      (P < 0.05). Spleen index increased (P < 0.05) in the CB2 group. Hens fed with C.
      butyricum reduced (P > 0.05) the population of E. coli, while Bifidobacterium
      counts increased quadratically and maximized in the CB2 group (P < 0.05). In
      conclusion, the results indicated that dietary supplementation with C. butyricum
      (5 * 104 or 1 * 105 cfu/g) could improve laying performance and egg quality by
      promoting immune function, enhancing antioxidative capacity, and benefiting the
      cecal microflora of laying hens in the late phase of production.

PMID- 30285188
TI  - The effect of some natural alternative to antibiotics on growth and changes in
      intestinal histology in broiler exposed to Salmonella challenge.
AB  - This study was conducted to find the effect of different feed additives on the
      production performance and intestinal histology in Salmonella challenged birds. A
      total of 600 day-old-broiler chicks (Ross 308) were assignment to 10 treatments.
      Each treatment was further divided into 10 replicates. The chicks were randomly
      divided into one of the following 10 treatments as follow: Negative control;
      positive control infected with Salmonella enterica subsp. typhimurium; T1,
      infected + avilamycin at the rate of 0.2 g/kg; T2, infected + probiotic having
      viable spores (2 * 107 CFU/g) of Bacillus subtilis (ATCC PTA-6737); T3, infected
      + Sanguinarine consisting of benzo phenanthridine alkaloids from Macleaya
      cordata; T4, B. subtilis (ATCC PTA-6737) + Sanguinarine; T5, infected + B.
      subtilis 500 g/T of feed (1.2 * 106 cfu/g); T6, prebiotic, Saccharomyces
      boulardii (1 * 108cfu/g); T7, infected + oregano at the rate of 1 g/kg; T8,
      infected + thermally processed clay calcium montmorillonite. The results showed
      that feed intake was significantly (P < 0.01) high in negative control and T2
      compared to the positive control. Body weight gain was significantly (P < 0.01)
      higher in negative control and significantly (P < 0.05) low in T8. Feed
      conversion ratio was significantly (P < 0.05) high in negative control and
      significanlty (P < 0.05) high in T6. Similarly, PEF was also significantly (P <
      0.05) high in negative control and significantly (P < 0.05) low in positive
      control and T8. Villus width was significantly (P < 0.05) high in negative
      control followed by T8. Dietary supplementation of different feed additives may
      be useful in broiler chicks challenged with Salmonella infection.

PMID- 30285185
TI  - Progressing super-enhancer landscape during mammary differentiation controls
      tissue-specific gene regulation.
AB  - The mammary luminal lineage relies on the common cytokine-sensing transcription
      factor STAT5 to establish super-enhancers during pregnancy and initiate a genetic
      program that activates milk production. As pups grow, the greatly increasing
      demand for milk requires progressive differentiation of mammary cells with
      advancing lactation. Here we investigate how persistent hormonal exposure during
      lactation shapes an evolving enhancer landscape and impacts the biology of
      mammary cells. Employing ChIP-seq, we uncover a changing transcription factor
      occupancy at mammary enhancers, suggesting that their activities evolve with
      advancing differentiation. Using mouse genetics, we demonstrate that the
      functions of individual enhancers within the Wap super-enhancer evolve as
      lactation progresses. Most profoundly, a seed enhancer, which is mandatory for
      the activation of the Wap super-enhancer during pregnancy, is not required during
      lactation, suggesting compensatory flexibility. Combinatorial deletions of
      structurally equivalent constituent enhancers demonstrated differentiation
      specific compensatory activities during lactation. We also demonstrate that the
      Wap super-enhancer, which is built on STAT5 and other common transcription
      factors, retains its exquisite mammary specificity when placed into globally
      permissive chromatin, suggesting a limited role of chromatin in controlling cell
      specificity. Our studies unveil a previously unrecognized progressive enhancer
      landscape where structurally equivalent components serve unique and
      differentiation-specific functions.

PMID- 30285189
TI  - Opioid, antipsychotic and hypnotic use in end of life in long-term care
      facilities in six European countries: results of PACE.
AB  - Background: Opioids, antipsychotics and hypnotics are recommended for comfort
      care in dying. We studied their prescription during the last 3 days in residents
      deceased in the long-term care facility (LTCF). Methods: In a retrospective,
      cross-sectional survey in Belgium, England, Finland, Italy, the Netherlands and
      Poland, LTCFs, selected by proportional stratified random sampling, reported all
      deaths over the previous 3 months. The nurse most involved in the residents' care
      reviewed the chart for opioid, antipsychotic and hypnotic prescription, cause of
      death and comorbidities. Multivariable logistic regression was performed to
      adjust for resident characteristics. Results: Response rate was 81.6%. We
      included 1079 deceased residents in 322 LCTFs. Opioid prescription ranged from
      18.5% (95% CI: 13.0-25.8) of residents in Poland to 77.9% (95% CI: 69.5-84.5) in
      the Netherlands, antipsychotic prescription from 4.8% (95% CI: 2.4-9.1) in
      Finland to 22.4% (95% CI: 14.7-32.4) in Italy, hypnotic prescription from 7.8%
      (95% CI: 4.6-12.8) in Finland to 47.9% (95% CI: 38.5-57.3) in the Netherlands.
      Differences in opioid, antipsychotic and hypnotic prescription between countries
      remained significant (P < 0.001) when controlling for age, gender, length of
      stay, cognitive status, cause of death in multilevel, multivariable analyses.
      Dying from cancer showed higher odds for receiving opioids (OR 3.51; P < 0.001)
      and hypnotics (OR 2.10; P = 0.010). Conclusions: Opioid, antipsychotic and
      hypnotic prescription in the dying phase differed significantly between six
      European countries. Further research should determine the appropriateness of
      their prescription and refine guidelines especially for LTCF residents dying of
      non-cancer diseases.

PMID- 30285191
TI  - Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy.

PMID- 30285190
TI  - Web Exclusive. Annals Graphic Medicine - Excuse Me, Doctor, Just a Question ....

PMID- 30285192
TI  - Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy.

PMID- 30285193
TI  - Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy.

PMID- 30285194
TI  - Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy.

PMID- 30285195
TI  - Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy.

PMID- 30285196
TI  - Treatment-Free Remission After Second-Line Nilotinib Treatment.

PMID- 30285198
TI  - Impact of Primary Care Intensive Management on High-Risk Veterans' Costs and
      Utilization.

PMID- 30285197
TI  - Treatment-Free Remission After Second-Line Nilotinib Treatment.

PMID- 30285199
TI  - Impact of Primary Care Intensive Management on High-Risk Veterans' Costs and
      Utilization.

PMID- 30285200
TI  - Impact of Primary Care Intensive Management on High-Risk Veterans' Costs and
      Utilization.

PMID- 30285201
TI  - Impact of Primary Care Intensive Management on High-Risk Veterans' Costs and
      Utilization.

PMID- 30285202
TI  - Correction: Impact of Primary Care Intensive Management on High-Risk Veterans'
      Costs and Utilization.

PMID- 30285203
TI  - Correction: In the Clinic-Herpes Zoster.

PMID- 30285204
TI  - The Bell.

PMID- 30285205
TI  - Let Me Ring the Bell.

PMID- 30285206
TI  - Palliative.

PMID- 30285207
TI  - A Strawberry Milkshake.

PMID- 30285208
TI  - Should This Woman With Dense Breasts Receive Supplemental Breast Cancer
      Screening?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.
AB  - Breast cancer will develop in 12% of women during their lifetime and is the
      second leading cause of cancer death among U.S. women. Mammography is the most
      commonly used tool to screen for breast cancer. Considerable uncertainty exists
      regarding the age at which to begin screening and the optimal screening interval.
      Breast density is a risk factor for breast cancer. In addition, for women with
      dense breasts, small tumors may be missed on mammography and the sensitivity of
      screening is diminished. At the time of publication, 35 states had passed laws
      mandating that breast density be reported in the letters that radiologists send
      to women with their mammogram results. The mandated language may be challenging
      for patients to understand, and such reporting may increase worry for women who
      are told that their risk for breast cancer is higher than average on the basis of
      breast density alone. The U.S. Preventive Services Task Force and the American
      College of Radiology (ACR) have each issued guidelines that address breast cancer
      screening for women with dense breasts. Both organizations found insufficient
      evidence to recommend for or against magnetic resonance screening, whereas the
      ACR advises consideration of ultrasonography for supplemental screening. In this
      Beyond the Guidelines, 2 experts-a radiologist and a general internist-discuss
      these controversies. In particular, the discussants review the role of
      supplemental breast cancer screening, including breast ultrasonography or
      magnetic resonance imaging for women with dense breasts. Finally, the experts
      offer specific advice for a patient who finds her mammography reports confusing.

PMID- 30285209
TI  - Clostridioides difficile Infection.
AB  - Clostridioides difficile (formerly Clostridium difficile) infection is the most
      frequently identified health care-associated infection in the United States. C
      difficile has also emerged as a cause of community-associated diarrhea, resulting
      in increased incidence of community-associated infection. Clinical illness ranges
      in severity from mild diarrhea to fulminant colitis and death. Appropriate
      management of infection requires understanding of the various diagnostic assays
      and therapeutic options as well as relevant measures to infection prevention.
      This article provides updated recommendations regarding the prevention,
      diagnosis, and treatment of incident and recurrent C difficile infection.

PMID- 30285211
TI  - Annals for Educators - 2 October 2018.

PMID- 30285210
TI  - Web Exclusive. Annals On Call - Diagnosing Sepsis: Untangling Confusion Around
      qSOFA and SIRS.

PMID- 30285212
TI  - Appendix 1: Cancer of the Prostate: eUpdate published online 28 September 2017
      (http://www.esmo.org/Guidelines/Genitourinary-Cancers/Cancer-of-the-Prostate).

PMID- 30285213
TI  - Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 30285215
TI  - ESMO Guidelines Committee Disclosures.

PMID- 30285214
TI  - Soft tissue and visceral sarcomas: ESMO-EURACAN Clinical Practice Guidelines for
      diagnosis, treatment and follow-up.

PMID- 30285217
TI  - Appendix 2: Medullary Thyroid Cancer: eUpdate published online 19 February 2018 
      (http://www.esmo.org/Guidelines/Endocrine-and-Neuroendocrine-Cancers/Thyroid
      cancer).

PMID- 30285216
TI  - Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice
      Guidelines for diagnosis, treatment and follow-up.

PMID- 30285219
TI  - Waldenstrom's macroglobulinaemia: ESMO Clinical Practice Guidelines for
      diagnosis, treatment and follow-up.

PMID- 30285220
TI  - ESMO Guidelines Committee.

PMID- 30285221
TI  - Management of anaemia and iron deficiency in patients with cancer: ESMO Clinical
      Practice Guidelines.

PMID- 30285218
TI  - Bone sarcomas: ESMO-PaedCan-EURACAN Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 30285222
TI  - Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for
      diagnosis, treatment and follow-up.

PMID- 30285224
TI  - Missing Disclaimer.

PMID- 30285223
TI  - Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 30285225
TI  - Reducing Nicotine in Cigarettes to Minimally Addictive Levels: A New Frontier for
      Tobacco Control.

PMID- 30285230
TI  - Female adiposity and time-to-pregnancy: a multiethnic prospective cohort.
AB  - STUDY QUESTION: Are higher overall and central adiposity associated with reduced
      fecundability, measured by time-to-pregnancy (TTP), in Asian women? SUMMARY
      ANSWER: Higher overall adiposity, but not central adiposity, was associated with
      longer TTP in Asian women. WHAT IS KNOWN ALREADY: High body mass index (BMI) has
      been associated with a longer TTP, although the associations of body composition
      and distribution with TTP are less clear. There are no previous studies of TTP in
      Asian women, who have a relatively higher percentage of body fat and abdominal
      fat at relatively lower BMI. STUDY DESIGN, SIZE, DURATION: Prospective
      preconception cohort using data from 477 Asian (Chinese, Malay and Indian) women
      who were planning to conceive and enrolled in the Singapore PREconception Study
      of long-Term maternal and child Outcomes (S-PRESTO) study, 2015-2017.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Women's mean age was 30.7 years.
      Overall adiposity was assessed by BMI, sum of 4-site skinfold thicknesses (SFT)
      and total body fat percentage (TBF%, measured using air displacement
      plethysmography); central adiposity was assessed by waist circumference (WC),
      waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and A body Shape Index
      (ABSI). Pregnancy occurring within one year from recruitment was ascertained by
      ultrasonography. Those who did not conceive within one year of recruitment, were
      lost to follow-up, or initiated fertility treatment were censored. TTP was
      measured in cycles. Discrete-time proportional hazards models were used to
      estimate the fecundability ratio (FR) and 95% confidence interval (CI) for each
      anthropometric measure in association with fecundability, adjusting for
      confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to women with a normal
      BMI of 18.5-22.9 kg/m2, women with higher BMI of 23-27.4 and >=27.5 kg/m2 showed
      lower FR of 0.66 (95% CI 0.45, 0.97) and 0.53 (0.31, 0.89), respectively.
      Compared to women in the lowest quartile of SFT (25-52.9 mm), those in the
      highest quartile of >=90.1 mm showed lower FR of 0.58 (95% CI 0.36, 0.95).
      Compared to women in the lowest quartile of TBF% (13.6-27.2%), those in the upper
      two quartiles of 33.0-39.7% and >=39.8% showed lower FR of 0.56 (95% CI 0.32,
      0.98) and 0.43 (0.24, 0.80), respectively. Association of high BMI with reduced
      fecundability was particularly evident among nulliparous women. Measures of
      central adiposity (WC, WHR, WHtR, ABSI) were not associated with fecundability.
      LIMITATIONS REASONS FOR CAUTION: Small sample size could restrict power of
      analysis.The analysis was confined to planned pregnancies, which could limit
      generalizability of findings to non-planned pregnancies, estimated at around 44%
      in Singapore. Information on the date of last menstrual period for each month was
      not available, hence the accuracy of self-reported menstrual cycle length could
      not be validated, potentially introducing error into TTP estimation. Measures of
      exposures and covariates such as cycle length were not performed repeatedly over
      time; cycle length might have changed during the period before getting pregnant.
      WIDER IMPLICATIONS OF THE FINDINGS: Other than using BMI as the surrogate measure
      of body fat, we provide additional evidence showing that higher amounts of
      subcutaneous fat that based on the measure of SFT at the sites of biceps,
      triceps, suprailiac and subscapular, and TBF% are associated with longer TTP.
      Achieving optimal weight and reducing total percentage body fat may be a
      potential intervention target to improve female fertility. The null results
      observed between central adiposity and TTP requires confirmation in further
      studies. STUDY FUNDING/COMPETING INTEREST(S): This research is supported by
      Singapore National Research Foundation under its Translational and Clinical
      Research Flagship Programme and administered by the Singapore Ministry of
      Health's National Medical Research Council, (NMRC/TCR/004-NUS/2008; NMRC/TCR/012
      NUHS/2014). Additional funding is provided by the Singapore Institute for
      Clinical Sciences, Agency for Science Technology and Research (A*STAR),
      Singapore. Y.S.C., K.M.G., F.Y. and Y.S.L. have received reimbursement to speak
      at conferences sponsored by companies selling nutritional products. Y.S.C.,
      K.M.G. and S.Y.C. are part of an academic consortium that has received research
      funding from Abbott, Nutrition, Nestle and Danone. Other authors declared no
      conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

PMID- 30285232
TI  - The clinical utility of point-of-care tests for influenza in ambulatory care: A
      systematic review and meta-analysis.
AB  - Background: Point-of-care tests (POCTs) for influenza are diagnostically superior
      to clinical diagnosis, but their impact on patient outcomes is unclear. Methods:
      A systematic review of influenza POCTs versus usual care in ambulatory care
      settings. Studies were identified by searching six databases and assessed using
      the Cochrane risk of bias tool. Estimates of risk ratios (RR), standardised mean
      differences, 95% confidence intervals and I2 were obtained by random effects meta
      analyses. We explored heterogeneity with sensitivity analyses and meta
      regression. Results: 12,928 citations were screened. Seven randomised studies
      (n=4,324) and six non-randomised studies (n=4,774) were included. Most evidence
      came from paediatric emergency departments. Risk of bias was moderate in
      randomised studies and higher in non-randomised studies. In randomised trials,
      POCTs had no effect on admissions (RR 0.93, 95% CI 0.61-1.42, I2=34%), returning
      for care (RR 1.00 95% CI=0.77-1.29, I2=7%), or antibiotic prescribing (RR 0.97,
      95% CI 0.82-1.15, I2=70%), but increased prescribing of antivirals (RR 2.65, 95%
      CI 1.95-3.60; I2=0%). Further testing was reduced for full blood counts (FBC) (RR
      0.80, 95% CI 0.69-0.92 I2=0%), blood cultures (RR 0.82, 95% CI 0.68-0.99; I2=0%)
      and chest radiography (RR 0.81, 95% CI 0.68-0.96; I2=32%), but not urinalysis (RR
      0.91, 95% CI 0.78-1.07; I2=20%). Time in the emergency department was not
      changed. Fewer non-randomised studies reported these outcomes, with some findings
      reversed or attenuated (fewer antibiotic prescriptions and less urinalysis in
      tested patients). Conclusions: Point-of-care testing for influenza influences
      prescribing and testing decisions, particularly for children in emergency
      departments. Observational evidence shows challenges for real-world
      implementation.

PMID- 30285231
TI  - Cognitive control and network disruption in remitted depression: a correlate of
      childhood adversity.
AB  - Individuals in a major depressive episode often display impairment in cognitive
      control, and this impairment exists outside of the acute phase of illness.
      Impairment in cognitive control also has been associated with exposure to
      childhood adversity (CA). The current study examined whether exposure to CA can
      explain variance in a component of cognitive control-inhibitory control
      independent of diagnostic status in young adults with and without a history of
      depression. Healthy control individuals (n = 40) and individuals with remitted
      major depressive disorder (n = 53) completed a task measuring inhibitory control,
      reported level of CA and completed a scanning session to assess gray matter
      volume and resting state connectivity in regions associated with cognitive
      control. The results demonstrate that higher levels of CA were associated with
      poorer inhibitory control, reduced right middle frontal gyrus gray matter,
      decreased connectivity of salience and emotion networks and increased
      connectivity in cognitive control networks, even after controlling for diagnostic
      status, residual depression symptoms and current stressors. Together, the results
      suggest that inhibitory control impairment and intrinsic connectivity changes may
      be characterized as developmental sequelae of early stress exposure.

PMID- 30285233
TI  - Neuromuscular Attributes Associated With Lower Extremity Mobility Among Community
      Dwelling Older Adults.
AB  - Background: The Short Physical Performance Battery (SPPB) is advocated as a
      screening tool in geriatric care for predicting future disability. We aimed to
      identify the leg neuromuscular attributes to be targeted in rehabilitative care
      among older adults with poor SPPB scores. Methods: Boston Rehabilitative
      Impairment Study of the Elderly (Boston RISE) participants (n = 430) underwent
      assessment of neuromuscular attributes (leg strength, leg velocity, trunk
      extensor endurance, knee flexion range of motion [ROM], ankle ROM, and foot
      sensation). Linear regression models examined association between each
      neuromuscular attribute and SPPB, adjusting for age, race, gender, comorbidity,
      body mass index, depression, cognition, and other neuromuscular attributes.
      Results: Participants with 1 SD unit higher leg strength, leg velocity, and trunk
      extensor endurance had 0.52, 0.30, and 0.52 points higher SPPB total score.
      Participants with ankle ROM impairment and foot sensory loss had 0.43 and 0.57
      lower SPPB total score compared with those without these. Leg strength and trunk
      extensor endurance were associated with balance; leg velocity, trunk extensor
      endurance, and ankle ROM were associated with gait speed; and strength, trunk
      extensor endurance, knee ROM, and feet sensation were associated with chair stand
      score. Neuromuscular attributes, along with covariates, explained 40.4% of the
      variance in the total SPPB score, a substantial increase over the 22.7% variance
      explained by covariates alone. Conclusions: Neuromuscular attributes affect
      mobility performance in older patients as measured by the SPPB. Specific
      impairments are associated with poor performance in specific component scores.
      Assessment of the SPPB components and rehabilitation of associated impairments
      may help improve the functional performance among older adults.

PMID- 30285234
TI  - The latitude-dependent autoimmune disease risk genes ZMIZ1 and IRF8 regulate
      mononuclear phagocytic cell differentiation in response to vitamin D.
AB  - Epidemiological, molecular and genetic studies have indicated high serum vitamin
      D levels are associated with lower risk of several autoimmune diseases. The
      Vitamin D Receptor (VDR) binding sites in monocytes and dendritic cells (DCs) are
      more common in risk genes for diseases with latitude-dependence than in risk
      genes for other diseases. The transcription factor genes ZMIZ1 and IRF8 - risk
      genes for many of these diseases - have VDR binding peaks co-incident with the
      risk SNPs. We show these genes are responsive to vitamin D: ZMIZ1 expression
      increased and IRF8 expression decreased, and this response was affected by
      genotype in different cell subsets. The IL10/IL12 ratio in tolerogenic DCs
      increased with vitamin D. These data indicate that vitamin D regulation of ZMIZ1
      and IRF8 in DCs and monocytes contribute to latitude-dependent autoimmune disease
      risk.

PMID- 30285235
TI  - Nurses are critical in aiding patients transitioning to biosimilars in
      inflammatory bowel disease: education and communication strategies.
AB  - The increasing prevalence of inflammatory bowel disease and the high costs
      associated with biological therapies suggest that biologicals with lower costs,
      but no compromise on efficacy and safety, should be considered when developing a
      treatment plan for inflammatory bowel disease. Biosimilars offer a more cost
      effective alternative, and although the European Medicines Agency has approved
      the use of biosimilars for many indications, including inflammatory bowel
      disease, patients may be concerned about the safety and efficacy of these agents.
      The updated Nurses-European Crohn's and Colitis Organisation statements,
      published in March 2018, recommend that inflammatory bowel disease nurses
      facilitate patient choice of biological or biosimilar therapy. Nurses are pivotal
      in managing the challenges associated with patients transitioning to biosimilars.
      However, there is limited information available on how inflammatory bowel disease
      nurses can communicate the concept of biosimilars to patients and also on how
      best to support them before and during the switch from originators. This review
      article will focus on patients' concerns regarding biosimilars and describe
      considerations for nurses when supporting patients transitioning from originators
      to biosimilars. Through nurse-led patient education and the use of structured
      communication strategies as well as investment into managed switching programmes,
      patients will become more confident and adherent to their biosimilar therapy, and
      this may lead to overall reductions in healthcare expenditure for inflammatory
      bowel disease.

PMID- 30285236
TI  - Catfish mucus alters the Flavobacterium columnare transcriptome.
AB  - Columnaris disease, caused by Flavobacterium columnare, severely impacts the
      production of freshwater finfish species. Therefore, efforts to better understand
      the biological processes of F. columnare, including the formation of biofilms and
      their contribution to disease, are ongoing. In this study, we incubated F.
      columnare cultures with channel catfish mucus and used high-throughput RNA
      sequencing to evaluate global changes in gene expression. Our data show that
      mucus activates in vitro biofilm formation. The analysis of F. columnare
      transcriptomes after the addition of mucus revealed significant differentially
      expressed genes (DEGs) between the planktonic and biofilm states. DEGs common
      among all biofilms were enriched for gene ontology groups including signal
      transduction, ligand binding and cellular homeostasis and are likely necessary
      for biofilm formation. Iron acquisition systems included TonB-dependent receptor
      and ferroxidase genes were expressed among all biofilms, while siderophore
      synthesis genes were only expressed in mucus-stimulated biofilms. The current
      analysis of F. columnare transcriptomes adds valuable information about the basic
      biological processes that occur during the planktonic and biofilm states. This
      work serves as a basis for future studies on understanding how biofilms are
      established and how they contribute to disease progression.

PMID- 30285237
TI  - Genetic Diversity of Deformed Wing Virus From Apis mellifera carnica
      (Hymenoptera: Apidae) and Varroa Mite (Mesostigmata: Varroidae).
AB  - Deformed wing virus (DWV) is one of the most widespread viruses that infect honey
      bee colonies. The route of infection is directly through contaminated food,
      feces, and air, or indirectly through the varroa mite, which acts as a vector.
      Positive DWV samples were obtained from Carniolan honey bee (Apis mellifera
      carnica) colonies and of varroa mites from the whole territory of Slovenia during
      a survey between 2007 and 2014. Nucleotide sequences of 471 nucleotides for the L
      protein gene and 573 nucleotides for the helicase gene were compared. High
      genetic diversity was observed among these Slovenian Carniolan honey bee DWV
      field samples, as well as with almost all the strains previously found in other
      countries in Europe. Phylogenetic analyses in two regions of the viral genome
      show that several of the DWV strains obtained from honey bees and varroa are
      genetically very closely related, confirming the important role of varroa in the
      transmission of DWV. Identification of closely related sequences also confirmed
      that the same strains of DWV have been successfully transmitted between various
      honey bee colonies and apiaries. It has also been established that simultaneous
      infection, in one apiary, of honey bees with two or more different strains of DWV
      is quite frequent. This is phylogenetic study that compares honey bee and varroa
      DWV strains from Carniolan honeybees.

PMID- 30285238
TI  - N-acetylmannosamine (ManNAc) supports the growth of Borrelia burgdorferi in the
      absence of N-acetylglucosamine (GlcNAc).
AB  - Borrelia burgdorferi, the causative agent of Lyme disease, lacks the ability to
      biosynthesize many essential nutrients de novo, including N-acetylglucosamine
      (GlcNAc). This amino sugar is required for cell wall synthesis, and is a
      component of the complex growth medium used for in vitro propagation. When
      cultured without free GlcNAc, B. burgdorferi cells exhibit a unique biphasic
      growth pattern. We hypothesized that genes involved in the GlcNAc starvation
      response would be differentially expressed when compared to cells cultured in
      complete medium, and investigated this using transcriptomics. Twenty-one genes
      were differentially regulated in wild-type and starvation-adapted cells cultured
      without GlcNAc compared to wild-type cells cultured with GlcNAc. Of those, three
      genes involved in carbohydrate utilization were upregulated: bbb04 (chbC)
      encoding a subunit of the chitobiose transporter, bb0629 (fruA-2) encoding a
      putative carbohydrate transporter and bb0644 (nanE) encoding a putative GlcNAc-6
      phosphate-2-epimerase predicted to catalyze the conversion of N-acetylmannosamine
      6-phosphate (ManNAc-6-P) to GlcNAc-6-P. Quantitative RT-PCR was used to confirm
      differential expression of select genes, and substitution of free GlcNAc with
      free ManNAc resulted in growth to high cell density, suggesting B. burgdorferi
      cells can utilize free ManNAc for cell wall synthesis and energy production.

PMID- 30285240
TI  - Evaluation of Yellow Sticky Traps Baited With Citrus Scents, Coconut Oil, and
      Commercial Lures as a Simple Tool to Monitor Diaphorina citri (Hemiptera:
      Liviidae) Under Tropical Dry Forest Conditions.
AB  - Efficient, economic, and simple monitoring methods are important to develop
      successful integrated management for Asian citrus psyllid (ACP) especially in
      developing countries. Two 5-wk tests were carried out to study the capture of ACP
      adults using yellow sticky traps by adding commercial citrus fruit scents (lemon,
      tangerine, or orange) or commercial coconut oil (first test) and to compare these
      baits with commercial lures (Alpha Scents and Pest Wizard) (second test) under
      natural infestation conditions. In the first test, the following treatments were
      carried out: yellow sticky traps baited with 1) coconut oil; 2) lemon, tangerine,
      or orange commercial scents; or 3) unbaited yellow sticky tramps (control). In
      the second test, treatments were as follows: traps baited with 1) coconut oil; 2)
      lemon, tangerine, or orange commercial scents; 3) two different commercial lures
      (Pest Wizard and Alpha Scents); and 4) unbaited traps. In the first experiment,
      the results obtained showed that traps with a coconut oil lure captured 4.4 ACP
      adults per trap per week, whereas control traps caught 1 ACP adult. In the second
      test, coconut oil (4.5 adults per trap per week) and Alpha Scents (4.2
      individuals) lures also exhibited a higher capture in comparison to all citrus
      scents (3.1 individuals) and Pest Wizard (3.5 individuals), and control (2
      individuals). In conclusion, these results suggest that the use of commercial
      attractants, mainly coconut oil, can be more attractive than unbaited traps and
      this may be helpful for integrating into integrated pest management programs
      intended for ACP.

PMID- 30285241
TI  - Post-learning paradoxical sleep deprivation impairs reorganization of limbic and
      cortical networks associated with consolidation of remote contextual fear memory
      in mice.
AB  - Study Objectives: Paradoxical sleep (PS) has been shown to play an important role
      in memory, in particular in emotional memory processes. However, the involvement
      of this particular sleep stage in the systemic consolidation of remote (30 days
      old) memory has never been tested. We examined whether post-learning PS could
      play a role in the consolidation of remote fearful memory and in the brain
      network reorganization that depends on it. Methods: Mice were PS-deprived during
      6 hours after contextual fear conditioning using an automated method, and their
      memory was tested either 1 day or 30 days after learning. Brain activity during
      retrieval was assessed using the immediate early gene Egr1 (Zif 268) as a
      neuronal marker of activity. Results: We found that PS deprivation impaired the
      recall of remote (30 days)-but not recent (1 day)-memory. We also showed that the
      superficial layers of the anterior cingulate cortex were significantly less
      activated during the retrieval of remote memory after PS deprivation. In
      contrast, after such deprivation, retrieval of remote memory significantly
      activated several areas involved in emotional processing such as the CA1 area of
      the ventral hippocampus, the basolateral amygdala and the superficial layers of
      the ventral orbitofrontal cortex. By performing graph-theoretical analyses, our
      result also suggests that post-learning PS deprivation could impact the
      reorganization of the functional connections between limbic areas in order to
      reduce the level of global activity in this network. Conclusions: These findings
      suggest an important role for PS in the systemic consolidation of remote memory.

PMID- 30285239
TI  - High-resolution DNA quadruplex structure containing all the A-, G-, C-, T
      tetrads.
AB  - DNA can form diverse structures, which predefine their physiological functions.
      Besides duplexes that carry the genetic information, quadruplexes are the most
      well-studied DNA structures. In addition to their important roles in
      recombination, replication, transcription and translation, DNA quadruplexes have
      also been applied as diagnostic aptamers and antidisease therapeutics. Herein we
      further expand the sequence and structure complexity of DNA quadruplex by
      presenting a high-resolution crystal structure of DNA1 (5'-AGAGAGATGGGTGCGTT-3').
      This is the first quadruplex structure that contains all the internal A-, G-, C-,
      T-tetrads, A:T:A:T tetrads and bulged nucleotides in one single structure; as
      revealed by site-specific mutagenesis and biophysical studies, the central ATGGG
      motif plays important role in the quadruplex formation. Interestingly, our
      structure also provides great new insights into cation recognition, including the
      first-time reported Pb2+, by tetrad structures.

PMID- 30285242
TI  - Letter to the Editor: "Incidence of Hypoglycemia After Gastric Bypass vs Sleeve
      Gastrectomy: A Randomized Trial".

PMID- 30285243
TI  - Antibiotic treatment of gastroenteritis in primary care.
AB  - Background: Gastroenteritis (GE) is a frequent reason for consultating a general
      practitioner. Yet little is known about antibiotic prescribing in primary care
      patients with GE. In this study, we quantified empirical and targeted antibiotic
      treatment of GE, compliance with recommendations from primary care clinical
      practice guidelines (CPGs) and the degree of antimicrobial resistance in patients
      receiving diagnostic faeces testing (DFT). Methods: We performed a cohort study
      using routine care data of 160 general practitioners, including electronic
      patient records from 2013 to 2014. GE episodes were extracted and linked to
      microbiological laboratory records to retrieve results of DFT. For each episode,
      data on patient characteristics, DFT results including antimicrobial resistance
      testing, and antibiotic prescriptions were collected. Results: We identified 13
      217 GE episodes. Antibiotic treatment was prescribed in 1163 (8.8%) episodes,
      most frequently with metronidazole (n = 646, 4.9%), azithromycin (n = 254, 1.9%)
      or ciprofloxacin (n = 184, 1.4%). Treatment was empirical for 641 (5%) GE
      episodes, of which 30% (n = 191) followed the CPG-recommended antibiotic choice.
      Targeted treatment following DFT results was prescribed for 537 GE episodes (4%),
      of which 99% (n = 529) followed CPG recommendations. Non-susceptibility to first-
      or second-choice antibiotics was demonstrated in three Salmonella isolates (9%
      13% of all isolates) and one Campylobacter isolate (1%). Conclusions: Antibiotic
      treatment of GE in primary care is relatively infrequent, with 1 in 11 episodes
      treated. Empirical treatment was more frequent compared with targeted treatment
      and mostly with non-CPG-recommended antibiotics. However, treatment based upon
      DFT results followed CPG recommendations.

PMID- 30285244
TI  - Salivary cortisone to estimate cortisol exposure and sampling frequency required
      based on serum cortisol measurements.
AB  - Context: Population studies frequently measure cortisol as a marker of stress and
      excess cortisol is associated with increased mortality. Cortisol has a circadian
      rhythm and frequent blood sampling is impractical to assess exposure. We
      investigated measuring salivary cortisone and examined sampling frequency
      required to determine cortisol exposure. Methods: Serum and saliva with cortisol
      and cortisone measured by LC-MS/MS in independent cohorts. The relationship
      between serum cortisol and salivary cortisone was analysed in cohort 1 using a
      linear mixed effects model and resulting fixed effects component was applied to
      cohort 2. Saliva cannot easily be collected when sleeping so we determined
      minimum sampling required to estimate cortisol exposure (eAUC) using 24-hour
      cortisol profiles (AUC24) and calculated the relative error (RE - a measure
      similar to the coefficient of variation) for the eAUC. Results: >90% of
      variability in salivary cortisone could be accounted for by change in serum
      cortisol. A single serum cortisol measurement was a poor estimate of AUC24
      especially in the morning or last thing at night (RE > 68%), however 3 equally
      spaced samples gave a median RE of 0% (Interquartile range (IQR) between -15.6%
      and 15.1%). In patients with adrenal incidentalomas the eAUC based on 3 serum
      cortisol samples showed a difference between those with autonomous cortisol
      secretion and those without (p=0.03). Interpretation: Accepting that most people
      sleep 7-8 hours, using approximately 8-hourly salivary cortisone measurements
      provides a non-invasive method of estimating 24-hour cortisol exposure for
      population studies.

PMID- 30285245
TI  - Discovery of SERPINA3 as a candidate urinary biomarker of lupus nephritis
      activity.
AB  - Objectives: We used an unbiased proteomics approach to identify candidate urine
      biomarkers (CUBMs) predictive of LN chronicity and pursued their validation in a
      larger cohort. Methods: In this cross-sectional pilot study, we selected urine
      collected at kidney biopsy from 20 children with varying levels of LN damage
      (discovery cohort) and performed proteomic analysis using isobaric tags for
      relative and absolute quantification (iTRAQ). We identified differentially
      excreted proteins based on degree of LN chronicity and sought to distinguish
      markers exhibiting different relative expression patterns using hierarchically
      clustered log10-normalized relative abundance data with linked and distinct
      functions by biological network analyses. For each CUBM, we performed specific
      ELISAs on urine from a validation cohort (n = 41) and analysis of variance to
      detect differences between LN chronicity, with LN activity adjustment. We
      evaluated for CUBM expression in LN biopsies with immunohistochemistry. Results:
      iTRAQ detected 112 proteins in urine from the discovery cohort, 51 quantifiable
      in all replicates. Simple analysis of variance revealed four differentially
      expressed, chronicity-correlated proteins (P-values < 0.05). Further correlation
      and network analyses led to selection of seven CUBMs for LN chronicity. In the
      validation cohort, none of the CUBMs distinguished LN chronicity degree; however,
      urine SERPINA3 demonstrated a moderate positive correlation with LN histological
      activity. Immunohistochemistry further demonstrated SERPINA3 staining in proximal
      tubular epithelial and endothelial cells. Conclusion: We identified SERPINA3, a
      known inhibitor of neutrophil cathepsin G and angiotensin II production, as a
      potential urine biomarker to help quantify LN activity.

PMID- 30285246
TI  - CRISPRlnc: a manually curated database of validated sgRNAs for lncRNAs.
AB  - The CRISPR/Cas9 system, as a revolutionary genome editing tool for all areas of
      molecular biology, provides new opportunities for research on lncRNA's function.
      However, designing a CRISPR/Cas9 single guide RNA (sgRNA) for lncRNA is not easy
      with an unwarrantable effectiveness. Thus, it is worthy of collecting validated
      sgRNAs, to assist in efficiently choosing sgRNA with an expected activity.
      CRISPRlnc (http://www.crisprlnc.org or http://crisprlnc.xtbg.ac.cn) is a manually
      curated database of validated CRISPR/Cas9 sgRNAs for lncRNAs from all species.
      After manually reviewing more than 200 published literature, the current version
      of CRISPRlnc contains 305 lncRNAs and 2102 validated sgRNAs across eight species,
      including mammalian, insect and plant. We handled the ID, position in the genome,
      sequence and functional description of these lncRNAs, as well as the sequence,
      protoacceptor-motif (PAM), CRISPR type and validity of their paired sgRNAs. In
      CRISPRlnc, we provided the tools for browsing, searching and downloading data, as
      well as online BLAST service and genome browse server. As the first database
      against the validated sgRNAs of lncRNAs, CRISPRlnc will provide a new and
      powerful platform to promote CRISPR/Cas9 applications for future functional
      studies of lncRNAs.

PMID- 30285247
TI  - Mosquito (Diptera: Culicidae) Species Composition in Ovitraps From a Mesoamerican
      Tropical Montane Cloud Forest.
AB  - Knowledge about mosquito species diversity at tropical montane cloud forests
      (TMCFs) in Mesoamerica is scarce. Here, we present data on mosquito species
      richness from samples biweekly collected, from January to December 2017, in
      ovitraps installed in a TMCF patch at Vazquez de Coronado County, Costa Rica.
      Ovitraps were placed at 2.25, 1.50 and 0.75 m at 16 sampling points. During the
      study period we measured relative humidity and air temperature at each sampling
      point, and water temperature, volume and pH in each ovitrap. We collected a total
      of 431 mosquito larvae belonging to five taxonomic units, one identified to the
      genus level and four to the species level. The most common mosquito species was
      Culex bihaicolus Dyar & Nunez Tovar (Diptera: Culicidae), which accounted for
      nearly 80% (n = 344) of the collected mosquitoes. Culex nigripalpus Theobald
      (Diptera: Culicidae) was the only medically important species we found and it was
      collected both in the dry (January to March) and rainy season (April to
      December). Over 95% (n = 411) of the mosquitoes were collected during the rainy
      season and 60% (n = 257) at 0.75 m. Among the environmental variables that we
      measured, only water volume and pH were significantly (P < 0.05) different
      between the dry and rainy season, the former increasing and the later decreasing
      during the rainy season. These results suggest that rainfall plays a major role
      regulating the phenology of the sampled mosquito species and highlight the need
      to screen for pathogens in Cx. nigripalpus at the study area.

PMID- 30285248
TI  - Daily Links Between Sleep and Anger Among Spouses of Chronic Pain Patients.
AB  - Objectives: This study identified daily associations between sleep, emotion, and
      marital functioning in the context of chronic pain. Because spouses' sleep is
      compromised on nights when patients experience more pain, we set out to identify
      implications of spouses' sleep for their own emotion (anger) upon waking and
      marital interaction (marital tension) throughout the rest of the day. We further
      considered whether spouses' critical attitudes about patients' pain-related
      coping exacerbated associations between their sleep, morning anger, and marital
      tension. Method: Data came from a study of knee osteoarthritis patients (50+
      years old) and spouses (N = 138 couples) who completed daily diaries across 22
      days. Multilevel models were estimated to test hypotheses. Results: Spouses woke
      up angrier on mornings when they reported that their sleep was more unrefreshing
      than usual. This association was stronger among more critical spouses. Morning
      anger resulting from unrefreshing sleep, however, did not predict marital tension
      throughout the rest of the day. Discussion: Findings highlight the potential
      value of intervention efforts aimed at promoting spouses' sleep quality in an
      effort to offset negative emotional consequences that may undermine spouses' and
      patients' adjustment in the context of chronic pain.

PMID- 30285249
TI  - Important candidate genes for abdominal fat content identified by linkage
      disequilibrium and fixation index information.
AB  - Selection for rapid growth in chickens has always been accompanied by increased
      fat deposition and excessive fat deposition, especially abdominal fat, cannot
      only decrease feed efficiency but also cause many diseases. Finding the candidate
      genes associated with abdominal fat deposition is essential for breeding. To
      identify these candidate genes, we applied linkage disequilibrium and selection
      signature analysis using chicken 60 k single nucleotide polymorphism (SNP) chips
      in two broiler lines divergently selected for abdominal fat content for 11
      generations. After quality control, 46,033 SNPs were left for analysis. Using
      these SNPs, we found that r2 was 0.06 to 0.14 in the lean line and 0.07 to 0.13
      in the fat line for all 28 chromosomes (except GGA16). Pairwise SNP distances <25
      kb showed a mean r2 = 0.33 in the lean line and r2 = 0.32 in the fat line. The
      fixation index (FST) analysis was carried out and 46 SNPs with the top 0.1% of
      the FST value was detected as the loci with selection signatures. Besides FST,
      hapFLK was also used to detect selection signatures for abdominal fat content. A
      total of 11 genes, including transient receptor potential cation channel
      subfamily C member 4, estrogen related receptor gamma, fibroblast growth factor
      13, G-protein-signaling modulator 2, RAR related orphan receptor A, phospholipase
      A2 group X, mitochondrial ribosomal protein L28, metadherin, calcitonin receptor
      like receptor, serine/threonine kinase 39, and nuclear factor I A, were detected
      as the important candidate genes for abdominal fat deposition based on their
      basic functions. The results of the present study may benefit the understanding
      of genetic mechanism of abdominal fat deposition in chicken.

PMID- 30285251
TI  - Effect of vitamin E in ovo feeding to broiler embryos on hatchability, chick
      quality, oxidative state, and performance.
AB  - The objective of the present study was to ascertain the effect of in ovo feeding
      of vitamin E (VE) on the incubation results, quality, and oxidative state of
      newborn chicks and on the initial performance results. The design consisted of
      randomized blocks with treatments at different levels of VE (0.0, 27.5, 38.5,
      49.5, and 60.4 IU). On 17.5 d of embryonic development, 780 eggs underwent in ovo
      injection using a manual needle. VE supplementation of 60.4 IU provided the
      highest hatching rate (P < 0.05) and shortest hatch window (P < 0.05). Better
      results regarding chick physical quality were observed in groups supplemented
      with VE (body weight, length, newborn chick quality score) and higher chick
      weight/egg weight ratios (P < 0.05). VE inoculation did not have any effect on
      the chicks' immunological system (P > 0.05). Greater development of the small
      intestine (intestine weight/yolk free chick weight and higher villi in duodenum)
      and better feed conversion over all periods studied (1 to 7, 1 to 14, and 1 to 21
      d) were observed among chicks that received in ovo VE supplementation (P < 0.05).
      The total protein concentrations in the liver and striated breast skeletal muscle
      tissue were highest in chicks that received 60.4 IU of VE (P < 0.05). The highest
      catalase activity was observed in the livers of newborn chicks supplemented with
      60.4 IU of VE (P < 0.05). It was concluded that in ovo VE supplementation
      improved the chicks' oxidative state, which led to improvements in incubation
      results, chick quality and performance results.

PMID- 30285250
TI  - Cross-sectional associations of objectively-measured sleep characteristics with
      obesity and type 2 diabetes in the PREDIMED-Plus trial.
AB  - Study Objectives: To examine independent and combined associations of sleep
      duration and sleep variability with body composition, obesity and type 2 diabetes
      (T2D) in elders at high cardiovascular risk. Methods: Cross-sectional analysis of
      1986 community-dwelling elders with overweight/obesity and metabolic syndrome
      from PREDIMED-Plus trial. Associations of accelerometry-derived sleep duration
      and sleep variability with body mass index (BMI), waist circumference (WC) and
      body composition were assessed fitting multivariable-adjusted linear regression
      models. Prevalence ratios (PR) and 95% confidence intervals (CI) for obesity and
      T2D were obtained using multivariable-adjusted Cox regression with constant time.
      "Bad sleepers" (age-specific non-recommended sleep duration plus sleep
      variability above the median) and "good sleepers" (age-specific recommended sleep
      duration plus sleep variability below the median) were characterized by combining
      sleep duration and sleep variability, and their associations with these outcomes
      were examined. Results: One hour/night increment in sleep duration was inversely
      associated with BMI (beta -0.38 kg/m 2 [95% CI -0.54, -0.23]), WC (beta -0.86 cm
      [95% CI -1.25, -0.47]), obesity (PR 0.96 [95% CI 0.93, 0.98]), T2D (PR 0.93 [95%
      CI 0.88, 0.98]) and other DXA-derived adiposity-related measurements (android fat
      and trunk fat, all p < .05). Each 1-hour increment in sleep variability was
      positively associated with T2D (PR 1.14 [95% CI 1.01, 1.28]). Compared with "good
      sleepers," "bad sleepers" were positively associated with obesity (PR 1.12 [95%
      CI 1.01, 1.24]) and T2D (PR 1.62 [95% CI 1.28, 2.06]). Conclusions: This study
      revealed cross-sectional associations of sleep duration with adiposity parameters
      and obesity. Sleep duration and sleep variability were associated with T2D.
      Considering simultaneously sleep duration and sleep variability could have
      additional value, particularly for T2D, as they may act synergistically.

PMID- 30285252
TI  - Developing a Pain Intensity Measure for Persons with Dementia: Initial
      Construction and Testing.
AB  - Objective: The goal of this study was to identify a limited set of pain
      indicators that were most predicive of physical pain. We began with 140 items
      culled from existing pain observation tools and used a modified Delphi approach
      followed by statistical analyses to reduce the item pool. Methods: Through the
      Delphi Method, we created a candidate item set of behavioral indicators. Next,
      trained staff observed nursing home residents and rated the items on scales of
      behavior intensity and frequency. We evaluated associations among the items and
      expert clinicians' assessment of pain intensity. Setting: Four government-owned
      nursing homes and 12 community nursing homes in Alabama and Southeastern
      Pennsylvania. Participants: Ninety-five residents (mean age = 84.9 years) with
      moderate to severe cognitive impairment. Results: Using the least absolute
      shrinkage and selection operator model, we identified seven items that best
      predicted clinicians' evaluations of pain intensity. These items were rigid/stiff
      body or body parts, bracing, complaining, expressive eyes, grimacing, frowning,
      and sighing. We also found that a model based on ratings of frequency of
      behaviors did not have better predictive ability than a model based on ratings of
      intensity of behaviors. Conclusions: We used two complementary approaches-expert
      opinion and statistical analysis-to reduce a large pool of behavioral indicators
      to a parsimonious set of items to predict pain intensity in persons with
      dementia. Future studies are needed to examine the psychometric properties of
      this scale, which is called the Pain Intensity Measure for Persons with Dementia.

PMID- 30285253
TI  - Comparison of performance and feed digestibility of the non-antibiotic feed
      supplement (Novacid) and an antibiotic growth promoter in broiler chickens.
AB  - Antibiotic growth promoters have been widely used in poultry to improve overall
      performance. The emergence of antibiotic resistance has resulted in sanctions
      imposed on the use of antibiotics in poultry diets, and alternatives such as
      herbal extracts are being considered to improve growth performance. The aim of
      this study was to compare the performance and feed digestibility of the feed
      supplement Novacid, which contains organic acids, glucomannan, and
      phytochemicals, with that of the antibiotic growth promoter bacitracin methylene
      disalicylate (BMD) in commercial broiler chickens. Six hundred 1-d-old Ross *
      Ross 308 male broiler chicks were randomly and equally assigned to six treatment
      groups with five replicates each (20 chicks per replicate). The chicks were fed a
      corn-soybean meal basal diet, and divided into two groups: unchallenged and
      challenged with E. coli (400 mg/kg Escherichia coli inoculation). Each of these
      groups was divided into three study groups: untreated, treated with 0.05%
      Novacid, and treated with 400 mg/kg BMD. At day 42, inclusion of Novacid or BMD
      significantly (P < 0.05) improved the performance in the unchallenged groups
      relative to the control group. However, in E. coli-challenged groups, Novacid and
      BMD did not improve performance. Ileal digestibility of crude fat, crude protein,
      and gross energy were reduced in the Novacid group (P < 0.05). BMD and Novacid
      were equally effective in controlling ileal nutrient digestibility and feed
      coliform count (P < 0.05). Novacid reduced cecal E. coli and Salmonella count
      compared to BMD and control. Thus, a phytochemical feed supplement with organic
      acids and glucomannan could be an effective substitute for antibiotic growth
      promoters in broiler diets, but cannot replace antibiotics to counter potent
      infectious agents such as E. coli.

PMID- 30285254
TI  - Fruiting and sink competition.

PMID- 30285255
TI  - Altered Global Signal Topography and Its Different Regional Localization in Motor
      Cortex and Hippocampus in Mania and Depression.
AB  - Bipolar disorder (BD) is a complex psychiatric disorder characterized by dominant
      symptom swings across different phases (manic, depressive, and euthymic).
      Different symptoms in BD such as abnormal episodic memory recall and psychomotor
      activity have been related to alterations in different regions, ie, hippocampus
      and motor cortex. How the abnormal regional distribution of neuronal activity
      relates to specific symptoms remains unclear, however. One possible neuronal
      mechanism of the relationship is the alteration of the global distribution of
      neuronal activity manifested in specific local regions; this can be measured as
      the correlation between the global signal (GS) and local regions. To understand
      the GS and its relationship to psychopathological symptoms, we here investigated
      the alteration of both GS variance and its regional topography in healthy
      controls and 3 phases of BD. We found that the variance of GS showed no
      significant difference between the 4 groups. In contrast, the GS topography was
      significantly altered in the different phases of BD, ie, the regions showing
      abnormally strong topographical GS contribution changed from hippocampus (and
      parahippocampus/fusiform gyrus) in depression to motor cortex in mania.
      Importantly, topographical GS changes in these regions correlated with
      psychopathological measures in both depression and mania. Taken together, our
      findings demonstrate the central importance of GS topography for
      psychopathological symptoms. This sheds lights on the neuronal mechanisms of
      specific psychopathological symptoms in BD, and its relevance in the relationship
      between global and local neuronal activities for behavior in general.

PMID- 30285256
TI  - Response to letter: Incidence of Hypoglycemia After Gastric Bypass vs Sleeve
      Gastrectomy: A Randomized Trial.

PMID- 30285257
TI  - Food Consumption, Developmental Time, and Protein Profile of the Digestive System
      of the Red Palm Weevil, Rhynchophorus ferrugineus (Coleptera: Dryophthoridae)
      Larvae Reared on Three Different Diets.
AB  - The red palm weevil (RPW), Rhynchophorus ferrugineus Olivier (Coleoptera:
      Dryophthoridae) is one of the most dangerous pests of major cultivated palms
      including coconut, oil palm, and sago. The larval stage of the weevil causes the
      most destruction of the palms as it completely destroys the palm cabbage. In this
      study, the larvae were given three different diets-coconut cabbage, oil palm
      cabbage, and sago stem, under laboratory conditions for food consumption and
      developmental time experiment. The protein profiles of the digestive systems of
      the larvae fed on these three diets were also determined. Although the coconut
      diet was the most consumed by RPW larvae compared to oil palm and sago diets, the
      growth rate of RPW larvae on oil palm diet was however significantly shorter than
      those on the coconut and sago diets: the RPW only need 1 mo and 9 d to complete
      the larval duration. Proteins profiling of eight 2-DE gel protein spots that
      range 50-20 kDa were identified by mass spectrometry sequence analysis. Based on
      the Matrix Science Software, the most dominant protein was cationic trypsin.
      However, based on the NCBI BLAST tool, aminopeptidase N was the most dominant
      enzyme. This finding can lead to the development of pest control strategies based
      on the antinutritional protease inhibitors as potential biocontrol agents. Urgent
      action to find effective control methods should be taken seriously as this weevil
      is presumed to be one of the serious pests of oil palm industry in Malaysia.

PMID- 30285259
TI  - Zinc source influences the gene expression of zinc transporters in jejunum and
      cecal tonsils during broiler challenge with Eimeria maxima and Clostridium
      perfringens.
AB  - The objective of this experiment was to study the effects of dietary zinc (Zn)
      source on gene expression of Zn transporters (metallothionein [MT], ZIP 3, 5, 8,
      9, 10, 11, 13, and 14, and ZnT 1, 4, 5, 6, 7, 9, and 10) in the jejunum and cecal
      tonsils of broilers challenged with coccidia or coccidia plus Clostridium
      perfringens. A 2 * 2 factorial design was used with 2 Zn sources (90 mg Zn/kg
      from either ZnSO4 or an organic Zn, Bioplex(r) Zn) and challenged with
      approximately 5,000 oocysts of Eimeria maxima at 14 d of age with or without C.
      perfringens (108 CFU/bird) at 18, 19, and 20 d of age (8 pens per treatment and 8
      birds per pen) after which 1 bird/pen was sampled at 21 d of age. In the jejunum,
      co-infection resulted in higher ZnT 5 and 6 gene expression, while organic Zn fed
      birds had lower ZIP 5 and 11, and higher ZnT1. Additionally, an interaction of
      challenge by Zn source was noted wherein ZnT10 was unaffected by the C.
      perfringens in the organic Zn treatment but was 2.7-fold lower in the co-infected
      ZnSO4 fed birds. S100A9 gene expression, a biomarker of inflammatory response in
      necrotic enteritis, increased 2 and 2.8-fold in the cecal tonsils and jejunum
      with the co-infection, respectively. Supplementation with organic Zn lowered
      S100A9 by 1.9 and 4.4-fold in the cecal tonsils and jejunum, respectively, when
      birds were supplemented with ZnSO4. Notably, MT, ZIP 3, 8, 9, 10, 13, or 14, and
      ZnT 4, 7, and 9 were unaffected by Zn source and/or method of challenge. An
      interaction of challenge by Zn source was also noted for serum Zn concentration,
      which was reduced when birds were challenged with C. perfringens and fed ZnSO4
      but no difference between challenge method when birds were fed organic Zn. Based
      on the expression of ZnT and ZIP genes, more Zn trafficking due to treatment
      occured in the jejunum than cecal tonsils, but further studies are needed to
      ascertain how Zn source regulates intracellular free Zn concentrations and whole
      body Zn status during an enteric challenge.

PMID- 30285258
TI  - Transcriptomics-Based Identification of Aquaporin Diversity in the House Dust
      Mite Dermatophagoides farinae (Acariformes: Pyroglyphidae).
AB  - Aquaporin water channel proteins are highly conserved across many diverse
      species. Some evidence indicates that aquaporins in insects may contribute to
      insect-related mammalian diseases and inflammation, and thus these proteins may
      represent viable therapeutic targets. Here, we used RNA sequencing and
      bioinformatics to identify putative aquaporins from the house dust mite,
      Dermatophagoides farinae. Six putative aquaporins were identified based on
      sequence similarity with aquaporins from other species. These putative
      aquaporins, deposited in GenBank and named DerfAQP1-4 (KY231248, KY231249,
      KY231250, and KY231251, respectively), DerfAQP5.01, and DerfAQP5.02 (KY231252 and
      KY231253), were successfully cloned into a bacterial plasmid. The identification
      of full-length aquaporin sequences from D. farinae provides a foundation for
      future molecular and biochemical studies of these proteins in D. farinae and
      related species.

PMID- 30285261
TI  - Provision of Buprenorphine to Pregnant Women by For-Profit Clinics in an
      Appalachian City.
AB  - OBJECTIVES: This study was undertaken to confirm that patient reports on
      buprenorphine medication-assisted therapy in for-profit buprenorphine clinics in
      our community were personally costly. We contacted all 17 for-profit clinics in
      our community and confirmed the patient reports that a significant financial
      payment of <=$100 was required for each visit. We also found that tapering of
      buprenorphine dosage in pregnancy was offered by several of the clinics. METHODS:
      A telephone survey was conducted with the 17 for-profit buprenorphine clinics
      located in the Johnson City, Tennessee area. The clinic representative who
      answered the telephone was asked questions regarding patient costs for therapy
      and availability of tapering programs for pregnant women. RESULTS: Patient
      reports that the for-profit clinics are costly were confirmed. None of the
      clinics accepted insurance reimbursement of any type. The most common weekly
      costs were $100 per visit. A majority of clinics offered biweekly or monthly
      visits at significantly increased rates. Clinic representatives stated that a
      majority of clinics would consider buprenorphine tapering programs for pregnant
      women. CONCLUSIONS: The high cost of for-profit clinics is a barrier for patient
      access to medication-assisted therapy with buprenorphine. Tapering of
      buprenorphine dosage in pregnant women has penetrated buprenorphine management
      practice in our community. Further research is needed to determine whether
      elimination of cost barrier would have a positive effect on the rates of neonatal
      abstinence syndrome.

PMID- 30285260
TI  - Genome-Wide Association Study Detected Novel Susceptibility Genes for
      Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.
AB  - Genome-wide association studies (GWASs) have identified >100 susceptibility loci
      for schizophrenia (SCZ) and demonstrated that SCZ is a polygenic disorder
      determined by numerous genetic variants but with small effect size. We conducted
      a GWAS in the Japanese (JPN) population (a) to detect novel SCZ-susceptibility
      genes and (b) to examine the shared genetic risk of SCZ across (East Asian [EAS]
      and European [EUR]) populations and/or that of trans-diseases (SCZ, bipolar
      disorder [BD], and major depressive disorder [MDD]) within EAS and between EAS
      and EUR (trans-diseases/populations). Among the discovery GWAS subjects (JPN-SCZ
      GWAS: 1940 SCZ cases and 7408 controls) and replication dataset (4071 SCZ cases
      and 54479 controls), both comprising JPN populations, 3 novel susceptibility loci
      for SCZ were identified: SPHKAP (Pbest = 4.1 * 10-10), SLC38A3 (Pbest = 5.7 * 10
      10), and CABP1-ACADS (Pbest = 9.8 * 10-9). Subsequent meta-analysis between our
      samples and those of the Psychiatric GWAS Consortium (PGC; EUR samples) and
      another study detected 12 additional susceptibility loci. Polygenic risk score
      (PRS) prediction revealed a shared genetic risk of SCZ across populations (Pbest
      = 4.0 * 10-11) and between SCZ and BD in the JPN population (P ~ 10-40); however,
      a lower variance-explained was noted between JPN-SCZ GWAS and PGC-BD or MDD
      within/across populations. Genetic correlation analysis supported the PRS
      results; the genetic correlation between JPN-SCZ and PGC-SCZ was rho = 0.58,
      whereas a similar/lower correlation was observed between the trans-diseases (JPN
      SCZ vs JPN-BD/EAS-MDD, rg = 0.56/0.29) or trans-diseases/populations (JPN-SCZ vs
      PGC-BD/MDD, rho = 0.38/0.12). In conclusion, (a) Fifteen novel loci are possible
      susceptibility genes for SCZ and (b) SCZ "risk" effect is shared with other
      psychiatric disorders even across populations.

PMID- 30285262
TI  - Birth Weight and Risk of Childhood Acute Lymphoblastic Leukemia in Arizona,
      Illinois, and Kentucky.
AB  - OBJECTIVE: To confirm the previously reported increased risk of leukemia among
      macrosomic children (those with birth weight >4 kg). METHODS: Birth certificates
      of Arizona, Illinois, and Kentucky children diagnosed as having acute
      lymphoblastic leukemia (ALL) before age 5 years were matched with birth
      certificates from leukemia-free children of the same sex, race, and ethnicity who
      were born in the same county on or about the same day. Odds ratios (ORs) for ALL
      among children of low (<2.5 kg) or high (>4 kg) birth weight were calculated by
      conditional logistic regression. RESULTS: Children with high birth weight had an
      elevated risk of ALL in the first 5 years of life (OR 1.28, 95% confidence
      interval [CI] 1.01-1.61). The excess risk was confined to non-Hispanic whites (OR
      1.77, 95% CI 1.27-2.48), both boys (OR 1.57, 95% CI 1.01-2.45) and girls (OR
      2.10, 95% CI 1.26-3.52). CONCLUSIONS: This study confirms the association between
      high birth weight and ALL previously reported by other studies in children of
      European ancestry. The literature on maternal risk factors for both macrosomia
      and ALL is reviewed, with maternal overnutrition emerging as a plausible risk
      factor for both outcomes.

PMID- 30285263
TI  - Contemporary Geographic Variation and Sociodemographic Correlates of Hysterectomy
      Rates Among Reproductive-Age Women.
AB  - OBJECTIVE: For decades hysterectomy rates have famously demonstrated unexplained
      geographic variation. The aim of this study was to identify county-level
      correlates of hysterectomy rates among reproductive-age women. METHODS: Using
      county-level data from multiple sources, linked with claims-based surveillance
      data of every hysterectomy performed among women ages 20 to 44 in North Carolina
      from 2011 to 2013 (N = 7180), we explored social, economic, and healthcare
      factors associated with county-level rates. RESULTS: After accounting for spatial
      autocorrelation, county-level hysterectomy rates were negatively associated with
      county-level median household income, positively associated with the proportion
      married, and not associated with measures of healthcare capacity or access.
      CONCLUSIONS: This analysis provides preliminary evidence that contemporary
      hysterectomy use in North Carolina occurs along socioeconomic lines.

PMID- 30285264
TI  - Effects of Maternal Carbohydrate and Fat Intake on Fetal Telomere Length.
AB  - OBJECTIVES: Telomere length can be affected by dietary factors in adults. We
      investigated the association between maternal carbohydrate and fat intake during
      pregnancy and telomere length in neonatal cord blood leukocytes. We hypothesized
      that high fat consumption and high carbohydrate consumption would be associated
      with shortened fetal telomere length. METHODS: We collected umbilical cord blood
      at delivery from women admitted for labor and delivery in a university hospital
      (N = 62) and extracted genomic DNA using quantitative polymerase chain reaction.
      We quantified telomere length using the telomere-to-single copy gene ratio method
      (T:S ratio). High carbohydrate intake was defined as consumption of >175 g/day
      and high fat intake as >35 g/day. We performed generalized linear regression
      modeling and bootstrap statistical analyses to derive precise estimates of
      association. RESULTS: Of the 62 maternal-fetal dyads included in this study, 79%
      were classified as high carbohydrate consumers and 37% were classified as high
      fat consumers. High fat consumption had a significant negative effect on T:S
      ratio (P < 0.05). Although high carbohydrate consumption was associated with a
      decreased T:S ratio, this relation did not attain statistical significance.
      CONCLUSIONS: To our knowledge, this study is the first evidence of an association
      between maternal high fat consumption and shortened fetal telomere length. These
      findings could enhance our understanding of the role of maternal diet in fetal
      programming.

PMID- 30285265
TI  - Expenditures and Quality: Hospital- and Health System-Affiliated Versus
      Independent Physicians in Virginia.
AB  - OBJECTIVES: The American Medical Association has reported that 2016 was the first
      year in which fewer than half (47.1%) of all practicing physicians owned their
      own practice. Across the United States, there has been consolidation of
      physicians and hospital and health systems, resulting in questions about the
      effect of this on healthcare expenditures. The aim of this study was to compare
      the expenditures per patient between hospital- and health system-affiliated
      physicians and independent physicians. METHODS: The author used Virginia's new
      statewide all-payer claims database to analyze expenditures and quality for 3
      years for hospital- and health system-affiliated physicians versus independent
      physicians. The database had all claims statewide for Virginians with individual
      or group commercial insurance coverage: 1.95 million patients in 2013, 2 million
      in 2014, and 2.1 million in 2015. The average annual expenditure for each
      physician was adjusted for average patient condition burden (risk) and
      differences in geographic input costs using regression analysis. Measures of
      primary care quality were obtained from the claims data using evidence-based
      measures from national health quality organizations. RESULTS: Hospital- and
      health system-affiliated physicians had annual expenditures per patient ranging
      from 10.3% to 14.6% higher than independent physicians. Most of the measures of
      primary care quality were not significantly different. CONCLUSIONS: Virginia
      patients, employers, and managed care companies incurred higher per-patient
      expenditures with hospital and health system physicians than with independent
      physicians.

PMID- 30285266
TI  - Protocol to Improve Genotyping of Non-Small-Cell Lung Cancer Diagnosed Using EBUS
      TBNA.
AB  - OBJECTIVES: Targeted therapies for non-small-cell lung cancers (NSCLCs) are based
      on the presence of driver mutations such as epidermal growth factor receptor
      (EGFR) and the echinoderm microtubule-associated protein-like 4-anaplastic
      lymphoma kinase (EML4-ALK) translocation. Endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) is a first-line modality for
      diagnosing and staging NSCLC. A quality improvement protocol maximizing tissue
      acquisition for molecular analysis has not been previously described. METHODS: We
      instituted a standardized protocol designed from a multidisciplinary meeting of
      the pulmonology, oncology, and pathology departments for the acquisition and on
      site processing of samples obtained through EBUS-TBNA to improve the yield for
      genetic analysis of EGFR and ALK testing. RESULTS: Preprotocol there were 50
      NSCLCs (29 adenocarcinomas) and postprotocol there were 109 NSCLCs (52
      adenocarcinomas). A statistically significant increase in yield for molecular
      analysis was seen in both EGFR (36% preprotocol and 80% postprotocol, P < 0.01)
      and ALK (41% preprotocol and 80% postprotocol, P < 0.01). There was no difference
      in complications preprotocol and postprotocol. CONCLUSIONS: Implementation of a
      standardized protocol with EBUS-TBNA was associated with an increase in adequacy
      for molecular genetic analysis in NSCLC.

PMID- 30285267
TI  - Homicide in the South: Higher Rates Among Whites and Fewer Racial Disparities.
AB  - OBJECTIVE: Describe southern US homicide rates in whites and blacks between 1999
      and 2015. METHODS: The Centers for Disease Control and Prevention Multiple Cause
      of Death Files provided mortality rates and 95% confidence intervals (CIs) for
      non-Hispanic whites (NHW) as well as non-Hispanic blacks and African Americans
      (NHB). RESULTS: Overall, age-adjusted (1 to >=85 years) homicide was
      significantly higher in the South (7.6/100,000, 95% CI 7.6-7.7) than the rest of
      the United States (4.9/100,000, 95% CI 4.8-4.9) even though the southern rate
      among NHB (18.7/100,000, 95% CI 18.5-18.8) was lower than the rest of the United
      States (23.3/100,000, 95% CI 23.1-23.5). The overall southern NHB:NHW mortality
      rate ratio was 5.1 and 10.6 in the rest of the nation. Homicide rates among NHW
      men were higher in the South than in each of the other US Census areas, whereas
      corresponding rates among NHB men were lower. For both men and women the NHB:NHW
      mortality rate ratio was lower in the South than in any other region. In
      addition, homicide rates among NHB women in the South were equal to or lower than
      corresponding rates in the West and Midwest. Finally, higher rates for NHW in
      metropolitan areas led to overall higher NHW mortality rates and relatively low
      NHB:NHW rates. Southern NHW had a higher percentage of firearms-related homicides
      (58.4%) than the corresponding percentage in the rest of the United States
      (49.8%; P < 0.001). Southern NHB used firearms for 78.8% of homicides compared
      with 83.9% in the rest of the United States (P < 0.001). CONCLUSIONS: The overall
      high homicide rates in the southern United States were attributable to relatively
      higher NHW rates than those found in the rest of the country. Further research
      targeting the role of firearms as well as cultural and other issues could further
      the understanding of the interrelations of homicide with complex regional and
      cultural factors.

PMID- 30285268
TI  - Effects of Religious Involvement on HIV Management Outcomes Among HIV-Positive
      Adults in Central North Carolina.
AB  - OBJECTIVES: The goals of this pilot cross-sectional study were to determine the
      feasibility of and begin measuring the effect of religious institution
      affiliation on human immunodeficiency virus (HIV) clinical outcomes in the
      southern United States, a region marked by later initiation of antiretroviral
      therapy, higher HIV-related morbidity, and higher mortality rates than people
      living with HIV (PLWH) elsewhere in the country. It also is a region with a high
      density of religious institutions, which may facilitate improved health outcomes
      through leveraged social capital. Because spirituality is a personal construct
      and PLWH constitute a vulnerable population, we wanted to determine whether it
      would be feasible to survey patients about the topic. We hypothesized that PLWH
      would be willing to participate and that PLWH who report involvement in religious
      institutions would be more likely to have suppressed HIV viral loads (VLs) and
      better engagement in care than PLWH not involved in a religious institution.
      METHODS: Eligible participants were enrolled from the Wake Forest Infectious
      Diseases Specialty Clinic to complete structured interviews using validated
      measures of religious institution affiliation, spiritual well-being, social
      support, and HIV-related stigma. HIV VL and engagement in care (clinic no-show
      rate) data were abstracted from the electronic medical record. Descriptive
      statistics calculated the prevalence of religious institution involvement,
      outcomes of interest, and potential confounders. t Tests compared continuous
      outcomes assuming normality, chi2 tests compared binary outcomes, and the
      Wilcoxon Mann-Whitney test compared outcomes for non-normal data. RESULTS: Fifty
      participants completed the study (55% participation rate); 72% identified as male
      and 28% identified as female. A total of 48% of participants identified as
      black/African American and 44% identified as white. Participants who identified
      as men who have sex with men made up 34%. More black/African American
      participants than white participants reported religious institution affiliation
      (23%; P = 0.15). There was no statistically significant relation between
      religious institution affiliation and CD4 or VL; however, higher levels of social
      support and spiritual well-being predicted a lower clinic no-show rate (P =
      0.0077 and 0.0195, respectively). There was a trend toward greater perceived HIV
      related stigma and CD4 (P = 0.0845) as well as more emergency department visits
      (P = 0.0976). CONCLUSION: PLWH in a southern US clinic were willing to answer
      questions about their spirituality. Religious institution affiliation was not
      significantly related to virologic suppression or CD4 in this sample. Higher
      levels of self-reported social support (P = 0.0077) and spiritual well-being (P =
      0.0195) predict better clinic attendance. These results suggest that religious
      affiliation alone does not imply positive benefits for all. Social support and
      spiritual well-being, however obtained, predict engagement in care. The next
      steps should include a fully powered study to define the relations among social
      support, spiritual well-being, and relevant clinical outcomes. Our results also
      support further investigation of perceived HIV-related stigma and healthcare
      utilization, based on the trend toward significance between emergency department
      visits and stigma.

PMID- 30285269
TI  - Group Battlefield Acupuncture in Primary Care for Veterans with Pain.
AB  - OBJECTIVE: To obtain preliminary data on the short- and intermediate-term effects
      of battlefield acupuncture (BFA) on self-reported pain intensity in a relatively
      large cohort of veterans to assess whether a more comprehensive clinical trial
      evaluation is warranted. METHODS: The treatment, in an outpatient group setting,
      consisted of up to five auricular semipermanent needles inserted into each ear at
      prespecified points. Efficacy of treatment was measured by self-reported pain,
      using the Defense and Veterans Pain Rating Scale, just before treatment and at
      posttreatment days 0, 1, 7, and 30. RESULTS: A total of 112 patients attended the
      group clinics. The mean pretreatment pain score was 6.8, with an immediate
      postprocedure decrease of 2.4 points. The proportion of patients reporting
      decreased pain was 88.4%, 80.7%, 52.4%, and 51% at posttreatment days 0, 1, 7,
      and 30, respectively. CONCLUSIONS: The short- and intermediate-term beneficial
      effect of BFA on chronic pain is clinically meaningful. The large proportion of
      patients reporting decreased pain even 30 days after treatment suggests that the
      long-term effect of BFA merits further investigation.

PMID- 30285270
TI  - Mobile Health (mHealth) Use or Non-Use by Residents of West Virginia.
AB  - OBJECTIVE: To compare mobile health (mHealth) usage by residents of West Virginia
      with national estimates. METHODS: Pew Research Center data from its Internet and
      American Life Project were accessed for secondary data analysis. These data,
      available to the public, are a probability sample of Internet use in the United
      States, differences in use based on selected variables (eg, education, household
      income), and how usage affects the lives of Americans. Using SAS software,
      diagnostics were performed on the data, revealing that the variables of interest
      were prepared and represented without any need for information. Data were used as
      is, with categorical and continuous characteristics and stipulations being
      provided in accompanying documents from the Pew Research Center. RESULTS: The
      national sample consisted of 509 men and 557 women with an average age of 51.02
      years (standard deviation 17.04). The 30 West Virginia residents included 19
      women and 11 men (mean for age 48.10, standard deviation 15.30). When controlling
      for socioeconomic and demographics factors, the odds of a West Virginia resident
      using an mHealth device were 82% less than the rest of the country, a
      statistically significant association. Women in West Virginia were 52% more
      likely to access mHealth information than men, and an increase in age
      corresponded with increased mHealth usage. CONCLUSIONS: The lack of mHealth use
      by residents in West Virginia represents an opportunity for clinicians and
      scientists. The high rates of preventable diseases in the region could be more
      effectively managed with greater use of these technologies.

PMID- 30285271
TI  - Risk, Outcomes, and Predictors of Clostridium difficile Infection in Lymphoma: A
      Nationwide Study.
AB  - OBJECTIVE: The risk of Clostridium difficile infection (CDI) has not been well
      studied in patients with lymphoma. We thus sought to determine the risk of CDI in
      hospitalizations with lymphoma along with its trend, outcomes, and predictors
      using a large database. METHODS: Hospital discharge data from the Nationwide
      Inpatient Sample (NIS) from 2007 to 2011 were used for the study. Using the
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes, all adult patients aged 18 years or older having a primary diagnosis of
      lymphoma were queried for the presence of CDI as any of the secondary diagnoses.
      The risk of CDI in lymphoma and its yearly trend were assessed. We performed
      multivariate logistic regression to determine the independent risk factors of CDI
      in lymphoma. Furthermore, we studied mortality and other adverse outcomes of CDI
      in patients with lymphoma. RESULTS: There were 236,312 discharges (weighted) with
      the primary diagnosis of lymphoma. CDI was present in 2.13% of patients with
      lymphoma versus 0.8% in the nonlymphoma group (P < 0.001). On multivariate
      analysis, the significant predictors of CDI in lymphoma were presence of
      infection (odds ratio [OR] 3.1, 95% confidence interval [CI] 2.7-3.6), stem cell
      transplant (OR 2.7, 95% CI 2.3-3.4), graft-versus-host disease (OR 1.9, 95% CI
      1.4-2.8), race (Asian vs white, OR 1.6, 95% CI 1.1-2.4), chemotherapy (OR 1.6,
      95% CI 1.4-1.8), gastrointestinal surgery (OR 1.4, 95% CI 1.2-1.7), and Charlson
      Comorbidity Index (CCI) (CCI of 2 vs 0-1: OR 1.2, 95% CI 1.1-1.4; CCI of 3 vs 0
      1: OR 1.3, 95% CI 1.03-1.6). CDI in lymphoma was associated with worse hospital
      outcomes such as increased mortality (17% vs 8%), increased length of stay (23.6
      vs 9.9 days), mean total hospital charges ($197,015 vs $79,392), rate of
      intubation (13% vs 4% vs 13%), and rate of total parenteral nutrition (11% vs
      3%). CONCLUSIONS: Hospitalization with lymphoma was associated with an increased
      risk of CDI. The significant predictors for CDI in lymphoma were infection, stem
      cell transplant, graft-versus-host disease, race, chemotherapy, gastrointestinal
      surgery, and Charlson Comorbidity Index. CDI in lymphoma was associated with
      increased mortality and other adverse outcomes warranting a need of more
      vigilance for CDI in patients with lymphoma.

PMID- 30285272
TI  - A Professional Well-Being Continuum: Broadening the Burnout Conversation.

PMID- 30285273
TI  - Commentary on "A Professional Well-Being Continuum: Broadening the Burnout
      Conversation".

PMID- 30285274
TI  - Do Teaching-Focused Medical Schools Perpetuate the Thinking That Black Faculty
      Should Not Be Researchers?

PMID- 30285275
TI  - A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam.
AB  - Clobazam (CLB) is a 1,5-benzodiazepine that has been widely used as an anxiolytic
      and antiseizure drug (ASD) since it was first synthesized over 50 years ago. CLB
      was approved in the United States in 2011 as adjunctive therapy for seizures in
      patients >=2 years old with Lennox-Gastaut syndrome. CLB pharmacokinetics (PK)
      have been studied in single- and multiple-dose administrations in healthy
      subjects. Salient features include high bioavailability, linear PK, and
      negligible effects from coadministration of other ASDs. CLB is highly and
      extensively absorbed, with little effect from food; time to maximum plasma
      concentration is 0.5 to 4 hours following the dose. After CLB doses of 20 to 40
      mg/day, the volume of distribution is 99 to 120 L, with oral clearance ranging
      from 1.9 to 2.3 L/h. CLB is lipophilic and distributes throughout the body after
      oral administration. It is metabolized in the liver by cytochrome P450 (CYP)
      isoenzymes CYP3A, CYP2C19, and CYP2B6, and its main active metabolite is N
      desmethylclobazam. The half-life of CLB after a single oral dose ranges from 36
      to 42 hours; the half-life of N-desmethylclobazam ranges from 59 to 74 hours. The
      metabolites of CLB are primarily excreted renally. Population PK modeling using
      data from healthy subjects and patients with Lennox-Gastaut syndrome indicates
      that race, sex, age, weight, and renal function do not influence CLB PK. As CLB
      has been extensively studied since the 1970s, this review is meant to provide a
      consolidated and comprehensive resource on CLB PK for both prescribers and
      scientists alike.

PMID- 30285276
TI  - Dabigatran as a Treatment Option for Heparin-Induced Thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is a potentially serious adverse drug
      reaction that can result in lethal vascular thrombosis. Dabigatran is a direct
      thrombin inhibitor that might be useful in the management of HIT. This study
      evaluated the efficacy and safety of dabigatran in patients with HIT. We included
      43 patients in the study who received dabigatran for the management of suspected
      HIT, based on 4Ts (thrombocytopenia, timing of platelet count drop, thrombosis or
      other sequelae, and other causes of thrombocytopenia) scores. Three patients were
      excluded because they had received dabigatran with a creatinine clearance <15
      mL/min. Patients' records were analyzed longitudinally, with 12 months follow-up
      from the time of initiation of dabigatran, for occurrence of thrombosis,
      dabigatran-related complications, and outcome. Patients with chronic kidney
      disease, hepatic impairment, mechanical heart valves, active bleeding, and
      extremes of weights (<50 and >120 kg) were excluded from the study. Arterial
      thrombosis was not observed in any of our patients. The platelet counts
      normalized in all patients except for 2, which was attributed to the underlying
      comorbidities. We did not observe any hemorrhagic events or significant
      thrombosis during the follow-up period. Eight patients died from nonthrombotic
      causes, which were unrelated to adverse effects of dabigatran. Based on our
      findings, dabigatran could be considered a safe and effective agent in the
      management of HIT, particularly in the developing countries, where there could be
      issues with the cost and availability of other agents recommended for this
      condition. Further studies are needed to validate our findings.

PMID- 30285277
TI  - Predicting the time needed for environmental systematic reviews and systematic
      maps.
AB  - Systematic reviews (SRs) and systematic mapping aim to maximize transparency and
      comprehensiveness while minimizing subjectivity and bias. These are time
      consuming and complex tasks, so SRs are considered resource intensive, but
      published estimates of systematic-review resource requirements are largely
      anecdotal. We analyzed all Collaboration for Environmental Evidence (CEE) SRs (n
      = 66) and maps (n = 20) published from 2012 to 2017 to estimate the average
      number of articles retained at each review stage. We also surveyed 33 experienced
      systematic reviewers to collate information on the rate at which those stages
      could be completed. In combination, these data showed that the average CEE SR
      takes an estimated 164 d (full-time equivalent) (SD 23), and the average CEE
      systematic map (SM) (excluding critical appraisal) takes 211 d (SD 53). While
      screening titles and abstracts is widely considered time-consuming, metadata
      extraction and critical appraisal took as long or longer to complete, especially
      for SMs. Given information about the planned methods and evidence base, we
      created a software tool that predicts time requirements of a SR or map with
      evidence-based defaults as a starting point. Our results shed light on the most
      time-consuming stages of the SR and mapping processes, will inform review
      planning, and can direct innovation to streamline processes. Future predictions
      of effort required to complete SRs and maps could be improved if authors provide
      more details on methods and results.

PMID- 30285278
TI  - Leptin acts in the carotid bodies to increase minute ventilation during
      wakefulness and sleep and augment the hypoxic ventilatory response.
AB  - KEY POINTS: Leptin is a potent respiratory stimulant. A long functional isoform
      of leptin receptor, LepRb , was detected in the carotid body (CB), a key
      peripheral hypoxia sensor. However, the effect of leptin on minute ventilation
      (VE ) and the hypoxic ventilatory response (HVR) has not been sufficiently
      studied. We report that LepRb is present in approximately 74% of the CB glomus
      cells. Leptin increased carotid sinus nerve activity at baseline and in response
      to hypoxia in vivo. Subcutaneous infusion of leptin increased VE and HVR in
      C57BL/6J mice and this effect was abolished by CB denervation. Expression of
      LepRb in the carotid bodies of LepRb deficient obese db/db mice increased VE
      during wakefulness and sleep and augmented the HVR. We conclude that leptin acts
      on LepRb in the CBs to stimulate breathing and HVR, which may protect against
      sleep disordered breathing in obesity. ABSTRACT: Leptin is a potent respiratory
      stimulant. The carotid bodies (CB) express the long functional isoform of leptin
      receptor, LepRb , but the role of leptin in CB has not been fully elucidated. The
      objectives of the current study were (1) to examine the effect of subcutaneous
      leptin infusion on minute ventilation (VE ) and the hypoxic ventilatory response
      to 10% O2 (HVR) in C57BL/6J mice before and after CB denervation; (2) to express
      LepRb in CB of LepRb -deficient obese db/db mice and examine its effects on
      breathing during sleep and wakefulness and on HVR. We found that leptin enhanced
      carotid sinus nerve activity at baseline and in response to 10% O2 in vivo. In
      C57BL/6J mice, leptin increased VE from 1.1 to 1.5 mL/min/g during normoxia (P <
      0.01) and from 3.6 to 4.7 mL/min/g during hypoxia (P < 0.001), augmenting HVR
      from 0.23 to 0.31 mL/min/g/Delta 

PMID- 30285279
TI  - DNA prime-protein boost vaccine encoding HLA-A2, HLA-A24 and HLA-DR1 restricted
      epitopes of CaNA2 against visceral leishmaniasis.
AB  - Visceral leishmaniasis is a tropical and neglected disease with an estimated 200
      000-400 000 cases and 60 000 deaths worldwide each year. Currently, no clinically
      valid vaccine is available for this disease. In this study, we formulated DNA and
      protein vaccines encoding HLA-A2, HLA-A24 and HLA-DR1 restricted epitopes of
      CaNA2 against visceral leishmaniasis. We predicted the secondary and tertiary
      structures, surface properties, subcellular localization, potential binding sites
      and HLA-A2, HLA-A24 and HLA-DR1 restricted epitopes of CaNA2. The best candidate
      CpG ODN (2395, M362, D-SL03 or 685) was screened out as a DNA vaccine adjuvant.
      We also prepared Kmp-11 and Kmp-11/CaNA2 DNA and protein vaccines, respectively,
      for comparison. BALB/c mice were immunized with a DNA prime-protein boost
      immunization strategy and challenged with a newly isolated Leishmania strain from
      an individual with visceral leishmaniasis. The IgG antibody titers showed that
      our vaccine had strong immunogenicity with a long duration, especially cellular
      immunity. The spleen parasite burden of each group demonstrated that the CaNA2
      vaccine had a certain immune protective effect on visceral leishmaniasis in
      BALB/c mice, and the amastigote reduction rate reached 76%. Preliminary safety
      tests confirmed the safety of the vaccine. Our work demonstrates that the HLA-A2,
      HLA-A24 and HLA-DR1 restricted epitope CaNA2 DNA prime-protein boost vaccine may
      be a safe and effective epitope vaccine candidate against visceral leishmaniasis.

PMID- 30285280
TI  - Interfacial Electron Transfer of Ni2 P-NiP2 Polymorphs Inducing Enhanced
      Electrochemical Properties.
AB  - Heterointerface engineering can be used to develop excellent catalysts through
      electronic coupling effects between different components or phases. As one kind
      of promising Pt-free electrocatalysts for hydrogen evolution reaction (HER), pure
      phased metal phosphide exhibits the unfavorable factor of strong or weak H*
      adsorption performance. Here, 6 nm wall-thick Ni2 P-NiP2 hollow nanoparticle
      polymorphs combining metallic Ni2 P and metalloid NiP2 with observable
      heterointerfaces are synthesized. It shows excellent catalytic performance toward
      the HER, requiring an overpotential of 59.7 mV to achieve 10 mA cm-2 with a Tafel
      slope of 58.8 mV dec-1 . Density functional theory calculations verify electrons'
      transfer from P to Ni at the heterointerfaces, which decreases the absolute value
      of H* adsorption energy and simultaneously enhance electronic conductivity. That
      is, the heterojunctions balance the metallic Ni2 P and the metalloid NiP2 to form
      an optimized phosphide polymorph catalyst for the HER. Furthermore, this
      polymorph combination is used with NiFe-LDH nanosheets to form an alkaline
      electrolyzer. It shows highly desirable electrochemical properties, which can
      reach 10 mA cm-2 in 1 m KOH at 1.48 V and be driven by an AAA battery with a
      nominal voltage of 1.5 V. The work about interfacial charge transfer might
      provide an insight into designing excellent polymorph catalysts.

PMID- 30285281
TI  - Cancer Statistics for Hispanics/Latinos, 2018.
AB  - Cancer is the leading cause of death among Hispanics/Latinos, who represent the
      largest racial/ethnic minority group in the United States, accounting for 17.8%
      (57.5 million) of the total population in the continental United States and
      Hawaii in 2016. In addition, more than 3 million Hispanic Americans live in the
      US territory of Puerto Rico. Every 3 years, the American Cancer Society reports
      on cancer occurrence, risk factors, and screening for Hispanics in the United
      States based on data from the National Cancer Institute, the North American
      Association of Central Cancer Registries, and the Centers for Disease Control and
      Prevention. For the first time, contemporary incidence and mortality rates for
      Puerto Rico, which has a 99% Hispanic population, are also presented. An
      estimated 149,100 new cancer cases and 42,700 cancer deaths will occur among
      Hispanics in the continental United States and Hawaii in 2018. For all cancers
      combined, Hispanics have 25% lower incidence and 30% lower mortality compared
      with non-Hispanic whites, although rates of infection-related cancers, such as
      liver, are up to twice as high in Hispanics. However, these aggregated data mask
      substantial heterogeneity within the Hispanic population because of variable
      cancer risk, as exemplified by the substantial differences in the cancer burden
      between island Puerto Ricans and other US Hispanics. For example, during 2011 to
      2015, prostate cancer incidence rates in Puerto Rico (146.6 per 100,000) were 60%
      higher than those in other US Hispanics combined (91.6 per 100,000) and 44%
      higher than those in non-Hispanic whites (101.7 per 100,000). Prostate cancer is
      also the leading cause of cancer death among men in Puerto Rico, accounting for
      nearly 1 in 6 cancer deaths during 2011-2015, whereas lung cancer is the leading
      cause of cancer death among other US Hispanic men combined. Variations in cancer
      risk are driven by differences in exposure to cancer-causing infectious agents
      and behavioral risk factors as well as the prevalence of screening. Strategies
      for reducing cancer risk in Hispanic populations include targeted, culturally
      appropriate interventions for increasing the uptake of preventive services and
      reducing cancer risk factor prevalence, as well as additional funding for Puerto
      Rico-specific and subgroup-specific cancer research and surveillance.

PMID- 30285282
TI  - Inducible nitric oxide synthase: An asset to neutrophils.
AB  - Neutrophils play a key role in innate immune responses against foreign intrusion
      and influence the subsequent instigation of adaptive immune response. Nitric
      oxide (NO) synthesized by neutrophil nitric oxide synthase (NOS) profoundly
      modulates their diverse physiological responsibilities furthermore encompassing
      pathological implications. Neutrophils are the active participants in diverse
      inflammatory and cardiovascular disorders but neutrophil nitric oxide synthase
      (NOS) remains enigmatic on various aspects. This review focuses on inducible NOS
      (iNOS) and makes an attempt to address its potential impact in neutrophil
      pathophysiology, their differentiation, functionality, and survival. We described
      the scenario from its expressional modulation, by pro- and anti-inflammatory
      cytokines governing the extent and duration of neutrophil immune response, to
      iNOS catalysis, the intracellular compartmentalization, and protein-protein
      interactions determining its microenvironment, activity and its contribution as a
      potential signaling protein apart from its role as signal transducer. Further,
      the relevance of investigating the unexplored facets of iNOS biology in
      neutrophils and possible prototypes of iNOS regulation is also exemplified in
      related cellular systems.

PMID- 30285283
TI  - Remaking the world in our own image: vulnerability, resilience and adaptation as
      historical discourses.
AB  - A warming climate and less predictable weather patterns, as well as an expanding
      urban infrastructure susceptible to geophysical hazards, make the world an
      increasingly dangerous place, even for those living in high-income countries. It
      is an opportune moment, therefore, from the vantage point of the second decade of
      the twenty-first century, to review the terms and concepts that have been
      employed regularly over the past 50 years to assess risk and to measure people's
      exposure to such events in the light of the wider geopolitical context. In
      particular, it is useful to examine 'vulnerability', 'resilience', and
      'adaptation', the principal theoretical concepts that, from an historical
      perspective, have dominated disaster studies since the end of the Second World
      War. In addition, it is valuable to enquire as to the extent to which such
      discourses were ideological products of their time, which sought to explain
      societies and their environments from the stance of competing conceptual
      frameworks.

PMID- 30285284
TI  - Single-Source Bismuth (Transition Metal) Polyoxovanadate Precursors for the
      Scalable Synthesis of Doped BiVO4 Photoanodes.
AB  - Single-source precursors are used to produce nanostructured BiVO4 photoanodes for
      water oxidation in a straightforward and scalable drop-casting synthetic process.
      Polyoxometallate precursors, which contain both Bi and V, are produced in a one
      step reaction from commercially available starting materials. Simple annealing of
      the molecular precursor produces nanocrystalline BiVO4 films. The precursor can
      be designed to incorporate a third metal (Co, Ni, Cu, or Zn), enabling the direct
      formation of doped BiVO4 films. In particular, the Co- and Zn-doped photoanodes
      show promise for photoelectrochemical water oxidation, with photocurrent
      densities >1 mA cm-2 at 1.23 V vs reversible hydrogen electrode (RHE). Using this
      simple synthetic process, a 300 cm2 Co-BiVO4 photoanode is produced, which
      generates a photocurrent of up to 67 mA at 1.23 V vs RHE and demonstrates the
      scalability of this approach.

PMID- 30285285
TI  - Putting Complex Older Persons First: How the Centers for Medicare and Medicaid
      Services 2019 Payment Proposal Fails Older Americans.
AB  - In July 2018, the Centers for Medicare and Medicaid Services (CMS) released its
      proposed Medicare Physician Fee Schedule rule for calendar year 2019 (MPFS2019).
      The proposal sets forth CMS-recommended updates to Medicare payment policies,
      payment rates, and quality provisions for services provided in the next calendar
      year. From year to year, the rule also can serve as a vehicle for soliciting
      input on new payment proposals and changes to existing policies. Among the
      payment and quality proposals in the MPFS2019 proposal, CMS proposed extensive
      changes to Current Procedural Terminology codes that are the framework for
      documentation and payment for office-based evaluation and management (E/M)
      services. The American Geriatrics Society (AGS) believes the proposed payment
      methodology changes for E/M services would have had a significant negative impact
      on care for older Americans. On September 10, 2018, the AGS submitted its
      comments on this proposal and other aspects of the rule, and the AGS also
      submitted a comment letter signed by 41 organizations from an AGS-led
      multispecialty coalition. The coalition also worked collaboratively on outreach
      to Congress, which included visits to Capitol Hill and a coalition letter
      stressing our collective support for reducing the burden of documentation for
      clinicians and our opposition to the proposed changes in payment methodology. In
      all letters, we noted that the AGS and members of our coalition hoped to work
      collaboratively with CMS and other stakeholders to develop a refined approach
      that would achieve the best possible outcomes for patients, particularly frail
      older Americans with multiple chronic conditions. In releasing their final
      MPFS2019, CMS postponed the E/M coding collapse for at least two years, a
      decision that speaks to the hard work of the AGS, its members, and the multi
      specialty coalition, and which opens the door for further discussions about the
      future of payment for E/M services so critical to older people.

PMID- 30285286
TI  - A Programmed Anti-Inflammatory Nanoscaffold (PAIN) as a 3D Tool to Understand the
      Brain Injury Response.
AB  - Immunology is the next frontier of nano/biomaterial science research, with the
      immune system determining the degree of tissue repair. However, the complexity of
      the inflammatory response represents a significant challenge that is essential to
      understand for the development of future therapies. Cell-instructive 3D culture
      environments are critical to improve our understanding of the link between the
      behavior and morphology of inflammatory cells and to remodel their response to
      injury. This study has taken two recent high-profile innovations-functional
      peptide-based hydrogels, and the inclusion of anti-inflammatory agents via
      coassembly-to make a programmed anti-inflammatory nanoscaffold (PAIN) with
      unusual and valuable properties that allows tissue-independent switching of the
      inflammatory cascade. Here, extraordinary durability of the anti-inflammatory
      agent allows, for the first time, the development of a 3D culture system that
      maintains the growth and cytoskeletal reorganization of brain tissue, while also
      facilitating the trophic behavior of brain cells for 22 d in vitro. Notably, this
      behavior was confirmed within an active scar site due to the unprecedented
      resilience to the presence of inflammatory cells and enzymes in the brain.
      Efficacy of the culture system is demonstrated via novel insights about
      inflammatory cell behavior, which would be impossible to obtain via in vivo
      experimentation.

PMID- 30285287
TI  - Impressum.

PMID- 30285288
TI  - World Arthritis Day 2018 - Perspectives on Rheumatic musculoskeletal diseases.

PMID- 30285289
TI  - Pretreated Macrophage-Membrane-Coated Gold Nanocages for Precise Drug Delivery
      for Treatment of Bacterial Infections.
AB  - Pathogenic bacterial infections and drug resistance make it urgent to develop new
      antibacterial agents with targeted delivery. Here, a new targeting delivery
      nanosystem is designed based on the potential interaction between bacterial
      recognizing receptors on macrophage membranes and distinct pathogen-associated
      molecular patterns in bacteria. Interestingly, the expression of recognizing
      receptors on macrophage membranes increases significantly when cultured with
      specific bacteria. Therefore, by coating pretreated macrophage membrane onto the
      surface of a gold-silver nanocage (GSNC), the nanosystem targets bacteria more
      efficiently. Previously, it has been shown that GSNC alone can serve as an
      effective antibacterial agent owing to its photothermal effect under near
      infrared (NIR) laser irradiation. Furthermore, the nanocage can be utilized as a
      delivery vehicle for antibacterial drugs since the gold-silver nanocage presents
      a hollow interior and porous wall structure. With significantly improved
      bacterial adherence, the Sa-M-GSNC nanosystem, developed within this study, is
      effectively delivered and retained at the infection site both via local or
      systemic injections; the system also shows greatly prolonged blood circulation
      time and excellent biocompatibility. The present work described here is the first
      to utilize bacterial pretreated macrophage membrane receptors in a nanosystem to
      achieve specific bacterial-targeted delivery, and provides inspiration for future
      therapy based on this concept.

PMID- 30285290
TI  - Mesoporous Organosilica Hollow Nanoparticles: Synthesis and Applications.
AB  - Hollow periodic mesoporous organosilicas (PMOs) with molecularly homogeneous
      organic functional groups in the inorganic pore walls are attracting more and
      more attention due to the high surface areas, tunable pore sizes, low densities,
      large cavities in the center, permeable thin shells, and versatile organic
      inorganic hybrid frameworks, which make them promising in a variety of
      applications including adsorption, catalysis, drug delivery, and
      nanotheranostics. Herein, recent advances in the synthesis of hollow PMO
      nanoparticles with various organic moieties are summarized, and the mechanism and
      new insights of synthesis approaches, including hard-core templating methods,
      liquid-interface assembly methods, and the interfacial reassembly and
      transformation strategy are discussed in-depth. Meanwhile, the design principles,
      properties, and synthetic strategies for some smart hollow architectures such as
      multishelled hollow PMOs, yolk-shell structured PMOs, and nonspherical hollow
      PMOs are discussed. Moreover, the typical applications of hollow PMO
      nanomaterials as nanoreactors for chemical transformations and nanoplatforms for
      biomedicine are summarized. Finally, the challenges and prospects for the future
      development of hollow PMOs are described.

PMID- 30285291
TI  - Impact of eosinophil-peroxidase (EPX) deficiency on eosinophil structure and
      function in mouse airways.
AB  - Eosinophil peroxidase (EPX) is a major constituent of the large cytoplasmic
      granules of both human and mouse eosinophilic leukocytes. Human EPX deficiency is
      a rare, autosomal-recessive disorder limited to the eosinophil lineage. Our
      intent was to explore the impact of EPX gene deletion on eosinophil content,
      structure, and function. In response to repetitive intranasal challenge with a
      filtrate of the allergen, Alternaria alternata, we found significantly fewer
      eosinophils peripherally and in the respiratory tracts of EPX-/- mice compared to
      wild-type controls; furthermore, both the major population (Gr1-/lo ) and the
      smaller population of Gr1hi eosinophils from EPX-/- mice displayed lower median
      fluorescence intensities (MFIs) for Siglec F. Quantitative evaluation of
      transmission electron micrographs of lung eosinophils confirmed the relative
      reduction in granule outer matrix volume in cells from the EPX-/- mice, a finding
      analogous to that observed in human EPX deficiency. Despite the reduced size of
      the granule matrix, the cytokine content of eosinophils isolated from allergen
      challenged EPX-/ - and wild-type mice were largely comparable to one another,
      although the EPX-/- eosinophils contained reduced concentrations of IL-3. Other
      distinguishing features of lung eosinophils from allergen-challenged EPX-/- mice
      included a reduced fraction of surface TLR4+ cells and reduced MFI for NOD1.
      Interestingly, the EPX gene deletion had no impact on eosinophil-mediated
      clearance of gram-negative Haemophilus influenzae from the airways. As such,
      although no clinical findings have been associated with human EPX deficiency, our
      findings suggest that further evaluation for alterations in eosinophil structure
      and function may be warranted.

PMID- 30285292
TI  - Risk communication and risk perception: lessons from the 2011 floods in Brisbane,
      Australia.
AB  - Risk communication and risk perception are critical factors in disaster
      management. Governments at all levels play a part in communicating risk, whereas
      the perception of risk entails active roles by community participants, including
      potential and actual victims of disasters. This paper discusses these matters in
      relation to the floods in Brisbane, Australia, in 2011. The findings are based on
      interviews with representatives of households whose dwellings or business
      premises were fully or partially inundated by the waters. The research shows how
      important it is to recognise the problems of institutional fragmentation in terms
      of communication and the active engagement of recipients in understanding and
      interpreting flood risk information (especially for slow-onset riverine flooding,
      such as that suffered by Brisbane). Locally targeted information on risk is of
      vital importance in avoiding the misinterpretation of warning information in
      relation to environmental cues and in promoting adequate responses. The paper
      concludes with some recommendations.

PMID- 30285293
TI  - Presynaptic loss of dynamin-related protein 1 impairs synaptic vesicle release
      and recycling at the mouse calyx of Held.
AB  - KEY POINTS: This study characterizes the mechanisms underlying defects in
      synaptic transmission when dynamin-related protein 1 (DRP1) is genetically
      eliminated. Viral-mediated knockout of DRP1 from the presynaptic terminal at the
      mouse calyx of Held increased initial release probability, reduced the size of
      the synaptic vesicle recycling pool and impaired synaptic vesicle recycling.
      Transmission defects could be partially restored by increasing the intracellular
      calcium buffering capacity with EGTA-AM, implying close coupling of Ca2+ channels
      to synaptic vesicles was compromised. Acute restoration of ATP to physiological
      levels in the presynaptic terminal did not reverse the synaptic defects. Loss of
      DRP1 impairs mitochondrial morphology in the presynaptic terminal, which in turn
      seems to arrest synaptic maturation. ABSTRACT: Impaired mitochondrial biogenesis
      and function is implicated in many neurodegenerative diseases, and likely affects
      synaptic neurotransmission prior to cellular loss. Dynamin-related protein 1
      (DRP1) is essential for mitochondrial fission and is disrupted in
      neurodegenerative disease. In this study, we used the mouse calyx of Held synapse
      as a model to investigate the impact of presynaptic DRP1 loss on synaptic vesicle
      (SV) recycling and sustained neurotransmission. In vivo viral expression of Cre
      recombinase in ventral cochlear neurons of floxed-DRP1 mice generated a
      presynaptic-specific DRP1 knockout (DRP1-preKO), where the innervated
      postsynaptic cell was unperturbed. Confocal reconstruction of the calyx terminal
      suggested SV clusters and mitochondrial content were disrupted, and presynaptic
      terminal volume was decreased. Using postsynaptic voltage-clamp recordings, we
      found that DRP1-preKO synapses had larger evoked responses at low frequency
      stimulation. DRP1-preKO synapses also had profoundly altered short-term
      plasticity, due to defects in SV recycling. Readily releasable pool size,
      estimated with high-frequency trains, was dramatically reduced in DRP1-preKO
      synapses, suggesting an important role for DRP1 in maintenance of release
      competent SVs at the presynaptic terminal. Presynaptic Ca2+ accumulation in the
      terminal was also enhanced in DRP1-preKO synapses. Synaptic transmission defects
      could be partially rescued with EGTA-AM, indicating close coupling of Ca2+
      channels to SV distance normally found in mature terminals may be compromised by
      DRP1-preKO. Using paired recordings of the presynaptic and postsynaptic
      compartments, recycling defects could not be reversed by acute dialysis of ATP
      into the calyx terminals. Taken together, our results implicate a requirement for
      mitochondrial fission to coordinate postnatal synapse maturation.

PMID- 30285295
TI  - 5,12-Diaminotetracenes: The Impact of Orbital Interactions between the Acene pi
      System and Amino Groups on Their Electronic States.
AB  - 5,12-Diamino-substituted tetracenes with various N-substituents have been
      prepared, and their molecular structural changes upon oxidation have been
      evaluated in association with their electronic structures. The N-substituents
      influence both the electronic and molecular structures of the oxidized species of
      5,12-diaminotetracenes. The tetracene moiety of 5,12-bis(N,N
      dianisylamino)tetracene retained its planarity during the course of two
      successive one-electron oxidations, whereas 5,12-bis(N,N-dimethylamino)tetracene
      and 5,12-bis(N-anisyl-N-methylamino)tetracene underwent substantial structural
      changes into butterfly like structures through a simultaneous two-electron
      oxidation process. The molecular structures in the oxidized states were closely
      related to the nature of the highest occupied orbitals, which were characterized
      by the extent of mixing between the fragment orbitals for the teracene moiety and
      the substituted amino groups in 5,12-diaminotetracenes. As a consequence, the
      present work revealed that the extent of folding deformation of the acene moiety
      in the oxidized diaminoacenes could be fine-tuned by varying the N-substituents.

PMID- 30285294
TI  - Spore Carbon from Aspergillus Oryzae for Advanced Electrochemical Energy Storage.
AB  - Development of novel advanced carbon materials is playing a critical role in the
      innovation of electrochemical energy storage technology. Hierarchical porous
      spore carbon produced by Aspergillus oryzae is reported, which acts as a
      biofactory. Interestingly, the spore carbon not only shows a porous maze
      structure consisting of crosslinked nanofolds, but also is intrinsically N and P
      dual doped. Impressively, the spore carbon can be further embedded with Ni2 P
      nanoparticles, which serve as porogen to form a highly porous spore carbon/Ni2 P
      composite with increased surface area and enhanced electrical conductivity. To
      explore the potential application in lithium-sulfur batteries (LSBs), the spore
      carbon/Ni2 P composite is combined with sulfur, forming a composite cathode,
      which exhibits a high initial capacity of 1347.5 mAh g-1 at 0.1 C, enhanced
      cycling stability (73.5% after 500 cycles), and better rate performance than the
      spore carbon/S and artificial hollow carbon sphere/S counterparts. The
      synergistic effect on suppressing the shuttle effect of intermediate polysulfides
      is responsible for the excellent LSBs performance with the aid of a physical
      blocking effect arising from the electrical maze porous structure and the
      chemical adsorption effect originating from N, P dual doping and polarized
      compound Ni2 P.

PMID- 30285297
TI  - Cryptic protein interactions regulate DNA replication initiation.
AB  - DNA replication is a fundamental biological process that is tightly regulated in
      all cells. In bacteria, DnaA controls when and where replication begins by
      building a step-wise complex that loads the replicative helicase onto chromosomal
      DNA. In many low-GC Gram-positive species, DnaA recruits the DnaD and DnaB
      proteins to function as adaptors to assist in helicase loading. How DnaA, its
      adaptors and the helicase form a complex at the origin is unclear. We addressed
      this question using the bacterial two-hybrid assay to determine how the
      initiation proteins from Bacillus subtilis interact with each other. We show that
      cryptic interaction sites play a key role in this process and we map these
      regions for the entire pathway. In addition, we found that the SirA regulator
      that blocks initiation in sporulating cells binds to a surface on DnaA that
      overlaps with DnaD. The interaction between DnaA and DnaD was also mapped to the
      same DnaA surface in the human pathogen Staphylococcus aureus, demonstrating the
      broad conservation of this surface. Therefore, our study has unveiled key protein
      interactions essential for initiation and our approach is widely applicable for
      mapping interactions in other signaling pathways that are governed by cryptic
      binding surfaces.

PMID- 30285296
TI  - Rationally Designed DNA-Origami Nanomaterials for Drug Delivery In Vivo.
AB  - The recent decades have seen a surge of new nanomaterials designed for efficient
      drug delivery. DNA nanotechnology has been developed to construct sophisticated
      3D nanostructures and artificial molecular devices that can be operated at the
      nanoscale, giving rise to a variety of programmable functions and fascinating
      applications. In particular, DNA-origami nanostructures feature rationally
      designed geometries and precise spatial addressability, as well as marked
      biocompatibility, thus providing a promising candidate for drug delivery. Here,
      the recent successful efforts to employ self-assembled DNA-origami nanostructures
      as drug-delivery vehicles are summarized. The remaining challenges and open
      opportunities are also discussed.

PMID- 30285298
TI  - A gene-stacking approach to overcome the trade-off between drought stress
      tolerance and growth in Arabidopsis.
AB  - The molecular breeding of drought stress-tolerant crops is imperative for stable
      food and biomass production. However, a trade-off exists between plant growth and
      drought stress tolerance. Many drought stress-tolerant plants overexpressing
      stress-inducible genes, such as DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN 1A
      (DREB1A), show severe growth retardation. Here, we demonstrate that the growth of
      DREB1A-overexpressing Arabidopsis plants could be improved by co-expressing
      growth-enhancing genes whose expression is repressed under drought stress
      conditions. We used Arabidopsis GA REQUIRING 5 (GA5), which encodes a rate
      limiting gibberellin biosynthetic enzyme, and PHYTOCHROME-INTERACTING FACTOR 4
      (PIF4), which encodes a transcription factor regulating cell growth in response
      to light and temperature, for growth improvement. We observed an enhanced biomass
      and floral induction in the GA5 DREB1A and PIF4 DREB1A double overexpressors
      compared with those in the DREB1A overexpressors. Although the GA5 DREB1A double
      overexpressors continued to show high levels of drought stress tolerance, the
      PIF4 DREB1A double overexpressors showed lower levels of stress tolerance than
      the DREB1A overexpressors due to repressed expression of DREB1A. A multiomics
      analysis of the GA5 DREB1A double overexpressors showed that the co-expression of
      GA5 and DREB1A additively affected primary metabolism, gene expression and plant
      hormone profiles in the plants. These multidirectional analyses indicate that the
      inherent trade-off between growth and drought stress tolerance in plants can be
      overcome by appropriate gene-stacking approaches. Our study provides a basis for
      using genetic modification to improve the growth of drought stress-tolerant
      plants for the stable production of food and biomass.

PMID- 30285299
TI  - Imiquimod 5% cream in occlusion, for the treatment of lentigo maligna: A new
      scheme of short cycles and the need for clinical trials.

PMID- 30285300
TI  - Brief Computer-Based Information Processing Measures are Linked to White Matter
      Integrity in Pediatric-Onset Multiple Sclerosis.
AB  - BACKGROUND AND PURPOSE: Pediatric-onset multiple sclerosis (POMS) is a
      demyelinating disorder with unique clinical challenges. A brief computer
      administered cognitive screening battery measuring processing speed (Cogstate)
      and the Brief International Cognitive Assessment in MS (BICAMS) detect cognitive
      impairment in POMS. The neuroanatomic correlates of these deficits are
      incompletely understood. The purpose of this study is to define the neuroanatomic
      underpinnings of deficits identified with cognitive screening batteries in POMS.
      METHODS: Participants with POMS and age-matched healthy controls (HCs) were
      screened with Cogstate and BICAMS. Diffusion tensor imaging assessed region-wise
      and tractography-based fractional anisotropy (FA). RESULTS: The POMS (n = 15) and
      HC (n = 21) groups were matched on age (mean ages 17.9 +/- 3.2 vs. 17.8 +/- 3.3
      years, respectively) and on an estimate of general intellectual functioning. The
      Cogstate composite revealed significant slowing in POMS relative to HCs (P =
      .004), but the BICAMS composite did not significantly distinguish the groups (P =
      .10). The Cogstate composite showed moderate-to-strong correlations with regional
      FA (r = -.67 to -.82) and significantly associated with uncinate fasciculus FA
      following multiple comparisons correction (P = .002) in POMS. However, the BICAMS
      composite measure showed only weak-to-moderate correlations with FA in POMS (r = 
      .19 to -.57), with none surviving multiple comparisons correction. CONCLUSIONS:
      Computer-administered measures of cognitive processing are particularly sensitive
      in POMS and are closely linked to white matter FA.

PMID- 30285301
TI  - Adjusting Aggregation Modes, Photophysical and Photovoltaic Properties of
      Diketopyrrolopyrrole-Based Small Molecules by Introducing B<-N Bonds.
AB  - The packing mode of small molecular semiconductors in thin films is an important
      factor that controls the performance of their optoelectronic devices. Designing
      and changing the packing mode via molecular engineering is challenging. Three
      structurally-related diketopyrrolopyrrole (DPP) based molecules are synthesized
      to study the effect of replacing C-C bonds by isoelectronic dipolar B<-N bonds.
      By replacing one of the bridging C-C bonds on the peripheral fluorene units of
      the DPP molecules by a coordinative B<-N bond and changing the B<-N bond
      orientation, the optical absorption, fluorescence, and excited state lifetime of
      the molecules can be tuned. The substitution alters the preferential aggregation
      of the molecules in solid state from H-type (for C-C) to J-type (for B<-N).
      Introducing B<-N bonds therefore provides a subtle way of controlling the packing
      mode. The photovoltaic properties of the DPP molecules are evaluated in bulk
      heterojunctions with a fullerene acceptor and reveal moderate performance as a
      consequence of suboptimal morphologies, bimolecular recombination, and triplet
      state formation.

PMID- 30285302
TI  - Catalyst-Free Oxytrifluoromethylation of Alkenes through Paired Electrolysis in
      Organic-Aqueous Media.
AB  - A mild, catalyst-free electrochemical oxytrifluoromethylation of alkenes has been
      developed. The procedure is based on the paired electrolysis of sodium triflinate
      and water in an undivided cell. Anodic oxidation of the triflinate anion
      generates trifluoromethyl radicals that react with the alkene. Water plays a dual
      role as oxidant for the cathode and nucleophile. The method has been utilized to
      prepare a diverse set of 1-hydroxy-2-trifluoromethyl compounds in moderate to
      excellent yields (27-94 %). Alcohols have also been tested as nucleophiles for
      this versatile method with moderate yields. Facile recycling of the electrolyte
      has been demonstrated, and application of electricity avoids the use of
      stoichiometric amounts of oxidizers in a safe and environmentally benign
      reaction.

PMID- 30285303
TI  - Ecological change alters the evolutionary response to harvest in a freshwater
      fish.
AB  - Harvesting can induce rapid evolution in animal populations, yet the role of
      ecological change in buffering or enhancing that response is poorly understood.
      Here, we developed an eco-genetic model to examine how ecological changes brought
      about by two notorious invasive species, zebra and quagga mussels, influence
      harvest-induced evolution and resilience in a freshwater fish. Our study focused
      on lake whitefish (Coregonus clupeaformis) in the Laurentian Great Lakes, where
      the species supports valuable commercial and subsistence fisheries, and where the
      invasion of dreissenid (zebra and quagga) mussels caused drastic shifts in
      ecosystem productivity. Using our model system, we predicted faster rates of
      evolution of maturation reaction norms in lake whitefish under pre-invasion
      ecosystem conditions when growth and recruitment of young to the population were
      high. Slower growth rates that occurred under post-invasion conditions delayed
      when fish became vulnerable to the fishery, thus decreasing selection pressure
      and lessening the evolutionary response to harvest. Fishing with gill nets and
      traps nets generally selected for early maturation at small sizes, except when
      fishing at low levels with small mesh gill nets under pre-invasion conditions; in
      this latter case, evolution of delayed maturation was predicted. Overall, the
      invasion of dreissenid mussels lessened the evolutionary response to harvest,
      while also reducing the productivity and commercial yield potential of the stock.
      These results demonstrate how ecological conditions shape evolutionary outcomes
      and how invasive species can have a direct effect on evolutionary responses to
      harvest and sustainability.

PMID- 30285305
TI  - Lisa Lieberman: Sex Ed in the U.S.-A Look Back (and Ahead).

PMID- 30285304
TI  - Macrophage polarization in human gingival tissue in response to periodontal
      disease.
AB  - OBJECTIVE: Although accumulating evidence indicates that macrophages are central
      players in the destructive and reparative phases of periodontal disease, their
      polarization states at different stages of periodontal inflammation remain
      unclear. METHODS: We collected gingival biopsies from patients with chronic
      periodontitis (P group), gingivitis (G group), or periodontally healthy
      individuals (H group). Polarized macrophages were identified through
      immunofluorescence. M1- and M2-related cytokines were detected by
      immunohistochemistry. RESULTS: Compared with the H group, the P group had more M1
      cells (higher M1/M2 ratio) and significantly higher TNF-alpha, IFN-gamma, IL-6,
      and IL-12 levels. Although the G group also exhibited higher TNF-alpha and IL-12
      levels than the H group, they had similar M1/M2 ratios. The M1/M2 ratio and IFN
      gamma and IL-6 levels were significantly higher in the P than the G group. Among
      M2-related cytokines, IL-4 levels were significantly higher in the G than the H
      group. The M1/M2 ratio was positively correlated with clinical probing depth
      (PD), and both were positively correlated with IFN-gamma and IL-6. PD was
      negatively correlated with IL-4. CONCLUSION: Macrophage polarization in gingival
      tissue may be responsible for the development and progression of inflammation
      induced tissue destruction, and modulating macrophage function may be a potential
      strategy for periodontal disease management.

PMID- 30285306
TI  - Critical Role for Saccharomyces cerevisiae Asc1p in Translational Initiation at
      Elevated Temperatures.
AB  - The eukaryotic ribosomal protein RACK1/Asc1p is localized to the mRNA exit
      channel of the 40S subunit but lacks a defined role in mRNA translation.
      Saccharomyces cerevisiae deficient in ASC1 exhibit temperature-sensitive growth.
      Using this null mutant, potential roles for Asc1p in translation and ribosome
      biogenesis are evaluated. At the restrictive temperature the asc1Delta null
      mutant has reduced polyribosomes. To test the role of Asc1p in ribosome
      stability, cryo-EM is used to examine the structure of 80S ribosomes in an
      asc1Delta yeast deletion mutant at both the permissive and nonpermissive
      temperatures. CryoEM indicates that loss of Asc1p does not severely disrupt
      formation of this complex structure. No defect is found in rRNA processing in the
      asc1Delta null mutant. A proteomic approach is applied to survey the effect of
      Asc1p loss on the global translation of yeast proteins. At the nonpermissive
      temperature, the asc1Delta mutant has reduced levels of ribosomal proteins and
      other factors critical for translation. Collectively, these results are
      consistent with recent observations suggesting that Asc1p is important for
      ribosome occupancy of short mRNAs. The results show the Asc1 ribosomal protein is
      critical in translation during heat stress.

PMID- 30285307
TI  - Regioselective Activation of a Sterically More Hindered C-C Bond of Biphenylenes
      Using an Alkene as Both a Directing Group and a Reaction Moiety.
AB  - The Rh-catalyzed intramolecular reaction of 1-(2-vinylaryl)-substituted
      biphenylenes was used to construct a dihydrobenzo[b]fluoranthene skeleton. This
      transformation was achieved by regioselective C-C bond cleavage of a sterically
      more hindered biphenylene site by using alkene as both a directing group and a
      reaction moiety. Furthermore, we measured and analyzed the photophysical
      properties of the new multicyclic fused compounds.

PMID- 30285308
TI  - Efficacy and safety of cyclosporine in Stevens-Johnson syndrome and toxic
      epidermal necrolysis.
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but
      life threatening cutaneous reactions that are most commonly caused by exposure to
      medications. This review assesses the efficacy and safety of cyclosporine therapy
      for SJS, TEN, and SJS/TEN overlap. A literature review was conducted in PubMed
      using the MeSH terms TEN, SJS, and cyclosporine. Five case series and one meta
      analysis were analyzed. From review of the existing literature, cyclosporine
      appears to not only have a mortality benefit in the treatment of SJS/TEN, but
      also a relatively safe side effect profile.

PMID- 30285309
TI  - Polymethylmethacrylate-induced nodules of the lips: Clinical presentation and
      management by intralesional neodymium:YAG laser therapy.
AB  - The lips are essential part of the beauty and attractiveness of the human face.
      Lip augmentation has become an increasingly used method to improve appearance.
      Soft tissue fillers are the most commonly used tools. Permanent fillers, however,
      have been associated with unwanted side effects after lip augmentation. In the
      present article the present authors will focus on permanent fillers based on
      polymethylmethacrylate (PMMA). The present authors provide a short review on PMMA
      fillers and known associated adverse events. The present authors provide a
      critical review of treatment options. Illustrated by clinical cases The present
      authors report our preferred treatment of PMMA nodules on lips by intralesional
      neodymium:YAG laser and blunt suction cannula with or without minor surgery.

PMID- 30285310
TI  - Copy number variations in a population with prune belly syndrome.
AB  - Prune Belly Syndrome (PBS) is a congenital multisystem myopathy with mild to
      lethal severity. While of uncertain etiology, 95% male predominance and familial
      occurrence suggest a genetic basis. As copy number variations (CNVs) can cause
      unexplained genetic disorders, we tested for novel CNVs in a large PBS
      population. We genotyped 21 unrelated PBS patients by high-resolution array
      comparative genomic hybridization (aCGH) and phenotyped using a novel PBS
      severity scoring system. Available parents were screened for detected CNV via
      quantitative PCR (qPCR). We additionally screened for recurrence of identified
      novel candidate CNVs on 106 PBS probands by qPCR. We identified 10 CNVs in 8 of
      21 PBS patients tested (38%). Testing confirmed inheritance from an unaffected
      biological parent in six patients; parental samples were unavailable in two
      probands. One candidate CNV includes duplication of the X-chromosome AGTR2 gene,
      known to function in urinary tract development. Subsequent screening of the
      larger PBS cohort did not identify any recurrent CNVs. Presence of CNV did not
      correlate with PBS severity scoring. CNVs were uncommon in this large PBS
      population, but analysis of identified variants may inform disease pathogenesis
      and reveal targets for therapeutic intervention for this rare, severe disorder.

PMID- 30285311
TI  - Construction of integrated microRNA and mRNA immune cell signatures to predict
      survival of patients with breast and ovarian cancer.
AB  - In the tumor microenvironment, immune cells have emerged as key regulators of
      cancer progression. While much work has focused on characterizing tumor-related
      immune cells through gene expression profiling, microRNAs (miRNAs) have also been
      reported to regulate immune cells in the tumor microenvironment. Using regression
      based computational methods, we have constructed for the first time, immune cell
      signatures based on miRNA expression from The Cancer Genome Atlas breast and
      ovarian cancer datasets. Combined with existing mRNA immune cell signatures, the
      integrated mRNA-miRNA leukocyte signatures are better able to delineate
      prognostic immune cell subsets within both cancers compared to the mRNA or miRNA
      signatures alone. Moreover, using the miRNA signatures, the anti-inflammatory M2
      macrophages emerged as the most significantly prognostic cell type in the breast
      cancer data (HR [hazard ratio]: 12.9; CI [confidence interval]: 3.09-52.9; P =
      4.22E-4), whereas the pro-inflammatory M1 macrophages emerged as the most
      prognostic immune cell type in the ovarian cancer data (HR: 0.2; CI: 0.04-0.56, P
      = 5.02E-3). These results suggest that our integrated miRNA and mRNA leukocyte
      signatures could be used to better delineate prognostic leukocyte subsets within
      cancers, whereas continued investigation may further support the regulatory
      relationships predicted between the miRNAs and immune cells found within our
      signature matrices.

PMID- 30285312
TI  - The Diradical-Dication Strategy for BODIPY- and Porphyrin-Based Dyes with Near
      Infrared Absorption Maxima from 1070 to 2040 nm.
AB  - Four stable boron dipyrromethene (BODIPY)- and porphyrin-based bis-arylamine
      diradical dications were synthesized by two-electron oxidation of their neutral
      molecules. The two BODIPY-based dications have open-shell singlet ground states.
      UV/Vis absorption spectra of all four dications showed large redshifts in the NIR
      region compared to their neutral precursors with absorption maxima at 1274 and
      1068 nm for the two BODIPY-based dications and 1746 and 2037 nm for the two
      porphyrin-based dications. Thus, two new types of NIR dyes with longer
      wavelengths are provided by the diradical-dication strategy, which can be applied
      for the generation of other NIR dyes with a range of different chromophores and
      auxochromes.

PMID- 30285313
TI  - Clinical presentation at initiation of maintenance dialysis and subsequent
      survival: A retrospective cohort study.
AB  - INTRODUCTION: Clinical practice guidelines increasingly favor a more symptom
      driven approach to maintenance dialysis initiation. But, little is known about
      the clinical presentation at dialysis initiation, such as the different kinds of
      signs and symptoms present at dialysis initiation, illness acuity at dialysis
      initiation, and how these aspects of the clinical presentation relate to
      subsequent survival. METHODS: This is a retrospective cohort study of a random
      sample of veterans who initiated dialysis between 2000 and 2009 at Veterans
      Affairs (VA) medical centers across the country (N = 1,691). We looked at
      associations between the clinical presentation (types of signs and/or symptoms
      and illness acuity) at the time of dialysis initiation and 1-year mortality.
      FINDINGS: The most common types of signs and/or symptoms at initiation were
      gastrointestinal (50.9%) and cardiopulmonary (48.7%). The crude mortality rate
      was 174.2 deaths per 1000 patients per year (95% CI 154.7, 196.1). Among
      different categories of signs and/or symptoms, only cardiopulmonary signs and/or
      symptoms were associated with a higher 1-year risk of mortality after initiation
      (risk ratio (RR) 1.32, 95% CI 1.05, 1.69) in adjusted analyses. Patients who were
      acutely ill at initiation were more likely to die during the following year as
      compared with those who initiated dialysis in the outpatient setting (RR 1.57,
      95% CI 1.15, 2.21). DISCUSSION: With the exception of cardiopulmonary signs
      and/or symptoms, most signs and/or symptoms documented around the time of
      dialysis initiation were not associated with an increased risk of death during
      the year after initiation. In contrast, whether patients were acutely ill at the
      time of initiation was strongly associated with an increased risk of death after
      initiation regardless of the specific signs and/or symptoms present. Limitations
      of this study include retrospective study design, residual confounding, and lack
      of generalizability to non-VA settings.

PMID- 30285314
TI  - Laser Irradiation of Gd-Si and Gd-Si-Ge Colloid Mixtures for the Fabrication of
      Compound Nanoparticles.
AB  - Binary (Gd5 Si4 , GdSi) and ternary (Gd5 Si2 Ge2 ) compound nanoparticles (NPs)
      were prepared by laser irradiation of a mixture of colloidal solutions containing
      NPs of the relevant elements. It is assumed that the compound NPs are formed by
      heating, co-melting, and chemical interactions in the alloyed droplets. The
      blackbody-like radiation of the heated NPs was used for temperature control of
      the NP-preparation process. The obtained results demonstrate that laser
      irradiation of colloidal NPs provides unique possibilities not only for the
      synthesis of compound NPs but also for control of their phase composition and
      size. The synthesized Gd-based compound NPs exhibited magnetic transition at an
      ordering temperature, TC , in the range of 310-320 K. Thus, the magnetic
      properties of the synthesized particles confirm their potential for biomedical
      applications, in particular, for magnetic hyperthermia treatment.

PMID- 30285315
TI  - First case of trastuzumab emtansine-associated hemorrhagic telangiectasias
      treated with propranolol.

PMID- 30285316
TI  - Endotoxin-Free Preparation of Graphene Oxide and Graphene-Based Materials for
      Biological Applications.
AB  - Due to their two-dimensional structure and unique properties, graphene and its
      derivatives have been extensively studied for their potential applications in
      various fields ranging from electronics to composites. Particularly, their high
      surface area, electrical conductivity, mechanical strength, dispersability in
      aqueous phase, and possibility of surface modification make them promising
      candidates for biomedical applications including biosensing, drug delivery,
      tissue engineering, cell imaging, and therapeutics. The functioning of graphene
      nanosheets in these applications is dependent on their structure and properties,
      which are mainly determined by their preparation and processing methods.
      Exfoliation techniques are the most common methods for preparation of graphene
      nanosheets for biomedical applications due to their high yield and scalability.
      Further modification of these methods is necessary to produce biocompatible and
      toxin-free graphene that can be safely incorporated into biological media. Here,
      we describe protocols for chemical and mechanical exfoliation of graphite to
      produce endotoxin-free and highly stable graphene oxide and graphene dispersions.
      Additional protocols are provided for proper pre- and post-processing of
      nanosheets and endotoxin measurement techniques. (c) 2018 by John Wiley & Sons,
      Inc.

PMID- 30285317
TI  - A Sensitive High-Throughput Screening Method for Identifying Small Molecule
      Stimulators of the Core Particle of the Proteasome.
AB  - Fluorescence resonance energy transfer (FRET) technology is a useful tool to
      monitor protein interactions as well as protease activity. We have recently
      reported a biochemical assay utilizing a FRET reporter peptide to monitor the
      activity of the 20S catalytic particle (20S CP) of the proteasome. This assay is
      designed specifically to have increased sensitivity to identify stimulators of
      the 20S CP, which may hold therapeutic potential to treat protein-accumulation
      diseases. The protocol described here details the necessary steps in synthesizing
      the FRET reporter peptide and performing the FRET assay with the 20S CP. (c) 2018
      by John Wiley & Sons, Inc.

PMID- 30285318
TI  - Combined detection of the ActRII-Fc fusion proteins Sotatercept (ActRIIA-Fc) and
      Luspatercept (modified ActRIIB-Fc) in serum by means of immunoaffinity
      purification, tryptic digestion, and LC-MS/MS.
AB  - Therapeutic proteins are a continuously growing class of pharmaceuticals and
      comprise several drug candidates with potential performance-enhancing properties.
      In particular, activin receptor competitors, such as the ActRII-Fc fusion
      proteins Sotatercept (ActRIIA-Fc) and Luspatercept (modified ActRIIB-Fc), have
      the potential for being misused as doping agents in sports as they were found to
      inhibit negative regulators of late-stage erythropoiesis. Within this study,
      ammonium sulfate precipitation, immunoaffinity purification, tryptic digestion,
      and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were employed to
      develop an assay for the combined detection of Sotatercept and Luspatercept in
      doping control serum samples. The assay was optimized, comprehensively
      characterized, and found to be fit-for-purpose for application to sports drug
      testing. It complements existing tests for ActRII-Fc fusion proteins and expands
      the range of available detection methods for novel protein therapeutics.

PMID- 30285319
TI  - Dinuclear Lanthanide Complexes Based on a Schiff-base Ligand: Free Lattice
      Solvent Inducing the Single Molecule Magnet Behavior of Dy2 Compound.
AB  - Syntheses, crystal structures and magnetic properties are described for a series
      of seven-coordinate dinuclear lanthanide complexes of compositions Dy2 L2 (1) (H3
      L=2-{[bis(2-hydroxy-3-ethoxybenzyl)(aminoethyl)amino]methyl}phenol) and Ln2 L2
      ?MeCN (Ln=Dy (2), Sm (3), Eu (4), Gd (5), Tb (6), Ho (7)). The reaction of Dy(NO3
      )3 ?6 H2 O with one equivalent of H3 L at 70  degrees C in DMF/EtOH under
      autogenous pressure gave compound 1. Complexes 2-7 were prepared by means of the
      same method as that used for 1, except DMF was replaced by MeCN as the reaction
      solvent and Dy(NO3 )3 ?6 H2 O was changed to the corresponding lanthanide salts.
      Complexes 1-7 possess the similar Ln2 cores bridged by MU2 -phenoxyl oxygen
      atoms. The slight difference between 1 and 2-7 arises from the existence of free
      MeCN molecule in 2-7. The purposeful introduction of solvent MeCN molecule
      changes the crystal system from triclinic for 1 to monoclinic for 2 and alters
      the Dy-O-Dy angles and Dy???Dy distances, consequentially resulting into dramatic
      influences on the magnetic properties of 1 and 2. Complex 1 shows no SMM
      character, while compound 2 with free MeCN molecule exhibits a field-induced slow
      magnetization relaxation behavior. Complete active space self-consistent field
      (CASSCF) calculations were performed on two Dy2 compounds to rationalize the
      observed difference in the magnetic behavior. Theoretical calculations reveal
      that the energy gap between the lowest two Kramers doublets of individual DyIII
      fragment for 2 is higher than those of 1 (1_a and 1_b). This conlusion is
      consistant with the experimental result that complex 2 exhibits better magnetic
      properties. This work proposes an ingenious strategy for inducing the SMM
      behavior in the Dy2 compounds.

PMID- 30285320
TI  - Anfractuous assemblies of IMP dehydrogenase and CTP synthase: new twists on
      regulation?
AB  - CTP synthase (CTPS) and IMP dehydrogenase (IMPDH) catalyse the rate-limiting
      steps of de novo CTP and guanosine nucleotide biosynthesis, respectively, and
      form filament assemblies in response to inhibitors. A recent study explores the
      morphology and dynamics of these assemblies using fluorescence and super
      resolution confocal microscopy with cell lines expressing CTPS1 and IMPDH2 fusion
      proteins. The formation and dismantling of mixed assemblies depends on nucleotide
      levels, suggesting a co-regulation function.

PMID- 30285321
TI  - Outcomes of 219 chronic myeloid leukaemia patients with additional chromosomal
      abnormalities and/or tyrosine kinase domain mutations.
AB  - INTRODUCTION: To confirm the role of additional chromosomal abnormalities (ACAs)
      and kinase domain (KD) mutations in the progression and outcomes of Chronic
      myeloid leukaemia (CML) patients and the connection between them, we analysed the
      ACAs and KD mutations of 219 CML patients admitted to our hospital. METHODS:
      Cytogenetic analysis of metaphases was performed to detect ACAs, and the BCR-ABL1
      KD was sequenced to detect KD mutations. RESULTS: Twenty-four patients (11.0%)
      had ACAs in addition to the BCR-ABL1 or t(9;22)(q34;q11) translocation. The most
      common abnormality was trisomy 8. Twelve different KD mutations were observed in
      13 out of 53 imatinib-resistant patients (24.5%). p.(Y235H) (n = 3; 23.07%),
      p.(F359V) and p.(T315I) (n = 2; 15.38%) presented most frequently. KD mutations
      subtypes (p.(E255K), p.(T315I), p.(F359V), p.(M244V) and p.(L298V)) coexisted
      with ACAs. The incidence of CML progression was 12/22 (54.5%) in the group of
      patients with ACAs and/or KD mutations and 2/143 (1.4%) in the group of patients
      without ACAs or KD mutations (CI 95%, P < 0.001) and was higher in the KD
      mutations group than in the ACAs group (P = 0.046). The group of patients with
      ACAs and/or KD mutations had more men than the group of patients without ACAs or
      KD mutations (P = 0.013). CONCLUSION: We conclude that ACAs and/or KD mutations
      are related to CML progression and are adverse outcome factors. Their presence
      exhibits gender differences and is more common in males. p.(E255K), p.(T315I),
      p.(F359V), p.(M244V) and p.(L298V) emerge more frequently when ACAs and KD
      mutations coexist.

PMID- 30285322
TI  - Neocortical Microdissection at Columnar and Laminar Resolution for Molecular
      Interrogation.
AB  - The heterogeneous organization of the mammalian neocortex poses a challenge for
      elucidating the molecular mechanisms underlying its physiological processes.
      Although high-throughput molecular methods are increasingly deployed in
      neuroscience, their anatomical specificity is often lacking. In this unit, we
      introduce a targeted microdissection technique that enables extraction of high
      quality RNA and proteins at high anatomical resolution from acutely prepared
      brain slices. We exemplify its utility by isolating single cortical columns and
      laminae from the mouse primary somatosensory (barrel) cortex. Tissues can be
      isolated from living slices in minutes, and the extracted RNA and protein are of
      sufficient quantity and quality to be used for RNA sequencing and mass
      spectrometry. This technique will help to increase the anatomical specificity of
      molecular studies of the neocortex, and the brain in general, as it is applicable
      to any brain structure that can be identified using optical landmarks in living
      slices. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30285323
TI  - Direct surgical transcatheter heart valve implantation in a calcified mitral
      valve.
AB  - Surgical transcatheter stent-valve implantation in severely calcific mitral
      valves represents a bail-out technique  for avoiding ventricular rupture and
      calcium embolization in patients with a high surgical risk profile. In this video
      tutorial, we present the transcatheter implantation of a valve in a severely
      calcific mitral valve annulus, under direct surgical vision, using an anchoring
      stitch technique to secure the stent-valve to the mitral annulus.

PMID- 30285324
TI  - The relationship between physical activity and diet, and overweight and obesity,
      in young people.
AB  - BACKGROUND: Childhood obesity has a worldwide association with serious health
      problems and complications that increase the risk of illness and death. AIM: To
      identify and assess the factors contributing to overweight and obesity among
      school students in north Jordan. METHOD: A descriptive cross-sectional study
      involving 1,554 students was conducted between October 2014 and February 2015.
      RESULTS: More than two thirds (70%) of participants were normal weight (5th
      percentile-<85th percentile), while 12% were overweight and 13% were obese. The
      prevalence of obesity was high (20%) among those eating snacks three times per
      day. The prevalence of overweight was high (12%) among those who followed no
      regular physical activity programme. CONCLUSION: Collaboration is required
      between policymakers, healthcare professionals, business and community leaders,
      schools and local organisations to create suitable environments that support
      healthy lifestyles for children and young people.

PMID- 30285326
TI  - Business Moves.

PMID- 30285325
TI  - Cabozantinib in Hepatocellular Carcinoma.

PMID- 30285327
TI  - Breast Cancer in Men.

PMID- 30285328
TI  - The Status of Current Respirator Regulations and Standards.
AB  - OSHA is considering some methods that will speed up the process of fit testing
      but still ensure that users are properly fitted with a particular respirator.

PMID- 30285329
TI  - Testing and Inspecting Your Emergency Equipment.
AB  - Here's what the key eyewash and shower standard, ANSI/ISEA Z358.1-2014, says
      about weekly tests and annual inspections of the equipment.

PMID- 30285330
TI  - A Shocking Turn of Events.

PMID- 30285331
TI  - Primary Prevention of Cardiovascular Disease with a Mediterranean Diet
      Supplemented with Extra-Virgin Olive Oil or Nuts.

PMID- 30285332
TI  - Primary Prevention of Cardiovascular Disease with a Mediterranean Diet
      Supplemented with Extra-Virgin Olive Oil or Nuts.

PMID- 30285333
TI  - Primary Prevention of Cardiovascular Disease with a Mediterranean Diet
      Supplemented with Extra-Virgin Olive Oil or Nuts.

PMID- 30285334
TI  - A Framework for Hazard Banding.
AB  - Exposure limits are absent for thousands of chemicals, creating a need for
      guidance that occupational exposure banding can help to fill, according to the
      authors of a new guidance document.

PMID- 30285335
TI  - Clearing the Air: The Importance of Filter Replacement for Welding Fume
      Extraction Systems.
AB  - For as much as you might be tempted to cut costs, filter replacement isn't a good
      place to do it. Not all replacement filters are alike, even if they are
      specifically designed to fit your system.

PMID- 30285337
TI  - Seizing on Seattle.
AB  - The year's biggest U.S industrial hygiene show, AIHce EXP docks in the Emerald
      City next month.

PMID- 30285336
TI  - Air Monitoring for Health and Safety of Industrial Workers.
AB  - Monitoring gas and vapor hazards is necessary to ensure workers' health and to
      see that the working environment is healthy.

PMID- 30285338
TI  - What You Don't Know About Combustible Dust, But Should.
AB  - By understanding the risks of this hazard and the regulations surrounding it, you
      can better equip your facility to prevent "near misses" so they never turn into
      catastrophic explosions.

PMID- 30285340
TI  - Three Groups to Consider in Emergency Communication Plans.
AB  - Knowing the types of emergencies to expect and what response is expected from
      each person makes it easier for employees to follow the instructions given by
      either on-site or external responders.

PMID- 30285339
TI  - Building Performance in Earthquakes and the U.S. Resiliency Council's Rating
      System.
AB  - The greatest value of a building rating system is one that meshes with economic
      decisions.

PMID- 30285341
TI  - Understanding Chemical Safety Following the Final GHS Deadline.
AB  - Don't view the conclusion of this round of GHS deadlines as the end of the
      process, but rather the beginning of the new state of HazCom and what OSHA now
      expects for compliance.

PMID- 30285404
TI  - How to Choose the Most Effective Hearing Protection?
AB  - Decision makers must consider that in many cases, workers have to wear hearing
      protection for eight hours.

PMID- 30285405
TI  - Measuring Behavioral Integrity of Safety Ownership and Improvement.
AB  - Where there is no behavioral integrity, trust, relationships, and maturing the
      culture all suffer. Progress will be at a standstill.

PMID- 30285406
TI  - Expanding Leadership Vision.

PMID- 30285407
TI  - Construction of Stimuli-Responsive Functional Materials via Hierarchical Self
      Assembly Involving Coordination Interactions.
AB  - Supramolecular self-assembly, which creates the ordered structures as a result of
      spontaneous organization of building blocks driven by noncovalent interactions
      (NCIs), is ubiquitous in nature. Recently, it has become increasingly clear that
      nature often builds up complex structures by employing a hierarchical self
      assembly (HSA) strategy, in which the components are brought together in a
      stepwise process via multiple NCIs. Inspired by the dedicated biological
      structures in nature, HSA has been widely explored to construct well-defined
      assemblies with increasing complexity. The employment of direct metal-ligand
      bonds to drive the formation of discrete metallosupramolecular architectures has
      proven to be a highly efficient strategy to prepare structurally diverse
      architectures like two-dimensional (2-D) polygons and three-dimensional (3-D)
      polyhedra with well-defined shapes, sizes, and geometries. Such well-defined
      organometallic assemblies provide an ideal platform for designing novel
      artificial supramolecular systems with the increasing complexity though HSA. The
      presence of a well-defined organometallic scaffold brings an additional dimension
      to the final nanoscale structures. Moreover, the multilevel dynamic nature of
      hierarchical self-assemblies brings more structural and functional possibilities
      of resultant supramolecular systems. This Account will focus on our recent
      advance on construction of stimuli-responsive functional materials through HSA
      involving coordination interactions. In our study, a series of functionalized
      metallacycles were first constructed through coordination-driven self-assembly
      (CDSA). Then, the secondary noncovalent interaction sites were integrated within
      the functionalized metallacycle system via either preassembly or postassembly
      approach. Different segments, such as alkyl chains, dendrimers, cholesteryl
      moiety, covalent macrocycles, and even polymeric fragments, which could provide
      hydrophobic and hydrophilic interactions, van der Waals forces, hydrogen bonding,
      CH-pi and pi-pi interactions, and host-guest interactions, have been utilized to
      provide the secondary NCIs. Further self-assembly of functionalized metallacycles
      gives rise to the formation of complex higher-order structures driven by other
      NCIs by taking advantages of orthogonal property of coordination bonds with other
      NCIs. By changing the type of additional NCIs embodied in building blocks,
      different supramolecular architectures, such as the ordered nanostructures,
      supramolecular polymers and gels, fluorescent materials and sensors, have been
      successfully prepared with the tailored chemical and physical properties. In
      particular, the dynamic nature of coordination bonds as well as other NCIs endows
      final assemblies with stimuli-responsive functions. Collectively, our studies
      suggest that combining coordination and other NCIs in a well-defined and precise
      manner is a highly efficient strategy to achieve the complex architectures and
      functional materials. Therefore, it is very promising to develop the desired
      functional materials with high precision and fidelity by employing HSA involving
      coordination interactions.

PMID- 30285408
TI  - Amphiphile-Induced Phase Transition of Liquid Crystals at Aqueous Interfaces.
AB  - Monolayer assemblies of amphiphiles at planar interfaces between thermotropic
      liquid crystals (LCs) and an aqueous phase can give rise to configurational
      transitions of the underlying LCs. A common assumption has been that a
      reconfiguration of the LC phase is caused by an interdigitation of the
      hydrophobic tails of amphiphiles with the molecules of the LC at the interface. A
      different mechanism is discovered here, whereby reorientation of the LC systems
      is shown to occur through lowering of the orientation-dependent surface energy of
      the LC due to formation of a thin isotropic layer at the aqueous interface. Using
      a combination of atomistic molecular dynamics simulations and experiments, we
      demonstrate that a monolayer of specific amphiphiles at an aqueous interface can
      cause a local nematic-to-isotropic phase transition of the LC by disturbing the
      antiparallel configuration of the LC molecules. These results provide new
      insights into the interfacial, molecular-level organization of LCs that can be
      exploited for rational design of biological sensors and responsive systems.

PMID- 30285409
TI  - Template-Free Synthesis of Two-Dimensional Fe/N Codoped Carbon Networks as
      Efficient Oxygen Reduction Reaction Electrocatalysts.
AB  - A direct pyrolysis and template-free synthesis strategy is demonstrated to
      synthesize the two-dimensional (2-D) Fe/N codoped carbon networks by virtue of 2
      D graphitic-carbon nitride (g-C3N4) intermediates derived from melamine. Because
      of the stabilization and steric hindrance of additional N ligands with
      bisnitrogen-containing groups (phenanthroline, phthalonitrile, and
      phenylenediamine), the thin graphitic-layered Fe/N codoped carbon materials have
      successfully inherited the 2-D morphology from the g-C3N4 intermediate after
      direct carbonization treatment. After the easy removal of inactive Fe particles,
      the resultant sample exhibits numerous well-dispersed Fe atoms embedded in the
      carbon layers with a hierarchical (meso- and micro-) porous structure. Owing to
      the high active site density and open porous structure, the thin graphitic
      layered Fe/N codoped carbon electrocatalysts exhibit superior oxygen reduction
      reaction performance (a half-wave potential of 0.88 V and a kinetics current
      density of 3.8 mA cm-2), even better than the commercial Pt/C catalysts (0.85 V
      and 1.6 mA cm-2, respectively). The facile and effective synthesis strategy
      without template to build the graphene-like nanoarchitectures inherited from the
      2-D intermediates will lead to a great development of 2-D carbon materials in
      various electrochemical applications.

PMID- 30285410
TI  - Doping beta-CoMoO4 Nanoplates with Phosphorus for Efficient Hydrogen Evolution
      Reaction in Alkaline Media.
AB  - Mass production of hydrogen by electrolysis of water largely hinges on the
      development of highly efficient and economical electrocatalysts for hydrogen
      evolution reaction (HER). Though having the merits of high earth abundance, easy
      availability, and tunable composition, transition-metal oxides are usually deemed
      as poor electrocatalysts for HER. Herein, we demonstrate that doping beta-CoMoO4
      nanoplates with phosphorus can turn them into active electrocatalysts for HER.
      Theoretical calculation and experimental studies unravel that enhanced electrical
      conductivity and optimized hydrogen adsorption free energy are major causes for
      the improvement of intrinsic activity. As a result, only an overpotential of 138
      mV is required to drive hydrogen evolving at a current density of 10 mA cm-2 in 1
      M KOH for P-doped beta-CoMoO4, which outstrips many recently reported transition
      metal oxides and is just slightly inferior to commercial Pt/C. This work opens a
      new route to tune the HER performance of transition-metal oxides.

PMID- 30285411
TI  - Soft Conducting Polymer Hydrogels Cross-Linked and Doped by Tannic Acid for
      Spinal Cord Injury Repair.
AB  - Mimicking soft tissue mechanical properties and the high conductivity required
      for electrical transmission in the native spinal cord is critical in nerve tissue
      regeneration scaffold designs. However, fabricating scaffolds of high
      conductivity, tissue-like mechanical properties, and excellent biocompatibility
      simultaneously remains a great challenge. Here, a soft, highly conductive,
      biocompatible conducting polymer hydrogel (CPH) based on a plant-derived
      polyphenol, tannic acid (TA), cross-linking and doping conducting polypyrrole
      (PPy) chains is developed to explore its therapeutic efficacy after a spinal cord
      injury (SCI). The developed hydrogels exhibit an excellent electronic
      conductivity (0.05-0.18 S/cm) and appropriate mechanical properties (0.3-2.2
      kPa), which can be achieved by controlling TA concentration. In vitro, a CPH with
      a higher conductivity accelerated the differentiation of neural stem cells (NSCs)
      into neurons while suppressing the development of astrocytes. In vivo, with
      relatively high conductivity, the CPH can activate endogenous NSC neurogenesis in
      the lesion area, resulting in significant recovery of locomotor function.
      Overall, our findings evidence that the CPHs without being combined with any
      other therapeutic agents have stimulated tissue repair following an SCI and thus
      have important implications for future biomaterial designs for SCI therapy.

PMID- 30285413
TI  - Fabrication of Supramolecular Bioactive Surfaces via beta-Cyclodextrin-Based Host
      Guest Interactions.
AB  - Supramolecular host-guest interactions provide a facile and versatile basis for
      the construction of sophisticated structures and functional assemblies through
      specific molecular recognition of host and guest molecules to form inclusion
      complexes. In recent years, these interactions have been exploited as a means of
      attaching bioactive molecules and polymers to solid substrates for the
      fabrication of bioactive surfaces. Using a common host molecule, beta
      cyclodextrin (beta-CD), and various guest molecules as molecular building blocks,
      we fabricated several types of bioactive surfaces with multifunctionality and/or
      function switchability via host-guest interactions. Other groups have also taken
      this approach, and several intelligent designs have been developed. The results
      of these investigations indicate that, compared to the more common covalent
      bonding-based methods for attachment of bioactive ligands, host-guest based
      methods are simple, more broadly ("universally") applicable, and allow convenient
      renewal of bioactivity. In this Spotlight on Applications, we review and
      summarize recent developments in the fabrication of supramolecular bioactive
      surfaces via beta-CD-based host-guest interactions. The main focus is on the work
      from our laboratory, but highlights on work from other groups are included.
      Applications of the materials are also emphasized. These surfaces can be
      categorized into three types based on: (i) self-assembled monolayers, (ii)
      polymer brushes, and (iii) multilayered films. The host-guest strategy can be
      extended from material surfaces to living cell surfaces, and work along these
      lines is also reviewed. Finally, a brief perspective on the developments of
      supramolecular bioactive surfaces in the future is presented.

PMID- 30285412
TI  - Omniphilic Polysaccharide-Based Nanocarriers for Modular Molecular Delivery in a
      Broad Range of Biosystems.
AB  - Self-adjusting omniphilic nanocarriers (OPNs) with a multisolvent aptitude were
      prepared via a Schiff base reaction between chitosan, a natural polysaccharide,
      and bioactive aldehydes. Experimental studies supported by atomistic molecular
      dynamics simulations revealed these OPNs can encapsulate insoluble molecular
      cargo, transport them in aqueous or lipid environments, and deliver them through
      cross-phase barriers. N-imine dynamic covalent bonds have been incorporated to
      endow the OPNs with pH responsiveness, also allowing the amplification of their
      bioactivity, as demonstrated in vitro with the ability to delay fungal
      proliferation in wheat grains. The reported OPNs hold remarkable potential as
      biocompatible nanocarriers for the effective delivery of active agents in
      agriculture, medicine, and cosmetics.

PMID- 30285414
TI  - Tandem Enzymatic Self-Assembly and Slow Release of Dexamethasone Enhances Its
      Antihepatic Fibrosis Effect.
AB  - Many chronic liver diseases will advance to hepatic fibrosis and, if without
      timely intervention, liver cirrhosis or even hepatocellular carcinoma. Anti
      inflammation could be a standard therapeutic strategy for hepatic fibrosis
      treatment, but a "smart" strategy of hepatic fibrosis-targeted, either self
      assembly or slow release of an anti-inflammation drug ( e.g., dexamethasone,
      Dex), has not been reported. Herein, we rationally designed a hydrogelator
      precursor Nap-Phe-Phe-Lys(Dex)-Tyr(H2PO3)-OH (1-Dex-P) and proposed a tandem
      enzymatic strategy of self-assembly and slow release of Dex, with which the
      precursor exhibited much stronger antihepatic fibrosis effect than Dex both in
      vitro and in vivo. Enzymatic and cell experiments validated that 1-Dex-P was
      first dephosphorylated by alkaline phosphatase to yield Nap-Phe-Phe-Lys(Dex)-Tyr
      OH (1-Dex), which self-assembled into nanofiber 1-Dex. The nanofiber was then
      hydrolyzed by esterase to transform into nanofiber 1, accompanied by slow release
      of Dex. We anticipate that our "smart" tandem enzymatic strategy could be widely
      employed to design more sophisticated drug delivery systems to achieve enhanced
      therapeutic efficacy than free drugs in the future.

PMID- 30285415
TI  - Tunable n-Type Doping of Carbon Nanotubes through Engineered Atomic Layer
      Deposition HfOX Films.
AB  - Although digital systems fabricated from carbon-nanotube-based field-effect
      transistors (CNFETs) promise significant energy efficiency benefits, realizing
      these benefits requires a complementary CNFET technology, i.e., CNFET CMOS,
      comprising both PMOS and NMOS CNFETs. Furthermore, this CNFET CMOS process must
      be robust ( e.g., air-stable), tunable ( e.g., ability to control CNFET threshold
      voltages), and silicon CMOS compatible (to integrate within existing
      manufacturing facilities and process flows). Despite many efforts, such a silicon
      CMOS compatible CNT doping strategy for forming NMOS CNFETs does not exist.
      Techniques today are either not air-stable (using reactive low work function
      metals), not solid-state or silicon CMOS compatible (employing soluble molecular
      dopants in ionic solutions), or have not demonstrated precise control over the
      amount of doping (for setting threshold voltage,  VT). Here, we demonstrate an
      electrostatic doping technique that meets all of these requirements. The key to
      our technique is leveraging atomic layer deposition (ALD) to encapsulate CNTs
      with nonstoichiometric oxides. We show that ALD allows for precise control of
      oxide stoichiometry, which translates to direct control of the amount of CNT
      doping. We experimentally demonstrate the ability to modulate the strength of the
      p-type conduction branch by >2500* (measured as the change in current at fixed
      bias), realize NMOS CNFETs with n-type conduction ~500* stronger than p-type
      conduction (also measured by the relative current at fixed biases), and tune VT
      over a ~1.5 V range. Moreover, our technique is compatible with other doping
      schemes; as an illustration, we combine electrostatic doping and low work
      function contact engineering to achieve CNFET CMOS with symmetric NMOS and PMOS (
      i.e., CNFET ON-current for NMOS and PMOS is within 6% of each other). Thus, this
      work realizes a solid-state, air-table, very large scale integration and silicon
      CMOS compatible doping strategy, enabling integration of CNFET CMOS within
      standard fabrication processes today.

PMID- 30285416
TI  - Serendipity in Catalysis Research: Boron-Based Materials for Alkane Oxidative
      Dehydrogenation.
AB  - Light olefins such as ethylene and propylene form the foundation of the modern
      chemical industry, with yearly production volumes well into the hundreds of
      millions of metric tons. Currently, these light olefins are mainly produced via
      energy-intensive steam cracking. Alternatively, oxidative dehydrogenation (ODH)
      of light alkanes to produce olefins allows for lower operation temperatures and
      extended catalyst lifetimes, potentially leading to valuable process
      efficiencies. The potential benefits of this route have led to significant
      research interest due to the wide availability of natural gas from shale
      deposits. Advances in this area have still not yielded catalysts that are
      sufficiently selective to olefins for industrial implementation, and ODH still
      remains a holy grail of selective alkane oxidation research. The main challenge
      in selective oxidation lies in preventing the overoxidation of the desired
      product, such as propylene during propane oxidation, to CO and CO2. Research into
      selective heterogeneous catalysts for the oxidative dehydrogenation of propane
      has led to the extensive use of vanadium oxide-based catalysts, and studies on
      the surface mechanism involved have been used to improve the catalytic activity
      of the material. Despite decades of research, however, selectivity toward
      propylene has not proven satisfactory at industrially relevant conversions. It is
      imperative for new catalytic systems that minimize product overoxidation to be
      developed for future applications of oxidative dehydrogenation processes. While
      rational catalyst design has been successful in developing homogeneous catalyst
      systems, its practical use in heterogeneous catalyst development remains modest.
      The complexity of surfaces with a variety of terminations and bulk structures,
      let alone their modification by the chemical potential of a reaction mixture,
      makes heterogeneous catalyst discovery serendipitous in many cases. The catalyst
      family presented in this Account is no exception. The importance of catalysis
      research lies in exploring the science behind serendipity. In this Account, we
      will first present our initial discovery of boron nitride (BN) as an unexpected
      catalyst for the oxidative dehydrogenation of light alkanes. Beyond its
      surprising activity, BN also drew interest due to its low selectivity to carbon
      oxides. This observation made BN distinct from previously studied metal oxide
      catalysts for selective alkane oxidation. We narrowed down its unique reactivity
      to the oxygen functionalization of the catalyst surface, particularly the
      formation of B-O species as probed by various spectroscopic techniques. In
      investigating the critical role of each of the structural elements during ODH, we
      discovered that not only BN but an entire class of boron-containing compounds are
      active and selective for the formation of propylene from propane. All these
      materials form a complex oxidized surface with a distribution of BO x surface
      sites. This discovery opens the doors to a new field of boron-based oxidation
      chemistry that currently has more questions than answers. We aim to make this
      Account a starting point for the research community to explore these new
      materials to understand their surface mechanisms and the surface species that
      offer a unique selectivity toward olefinic products. Effective use of these
      materials may lead to novel processes for efficient use of abundant light alkane
      resources by oxidation chemistry.

PMID- 30285417
TI  - Nonpolar-Oriented Wurtzite InP Nanowires with Electron Mobility Approaching the
      Theoretical Limit.
AB  - As an important semiconductor nanomaterial, InP nanowires (NWs) grown with a
      typical vapor-liquid-solid mechanism are still restricted from their low electron
      mobility for practical applications. Here, nonpolar-oriented defect-free wurtzite
      InP NWs with electron mobility of as high as 2000 cm2 V-1 s-1 can be successfully
      synthesized via Pd-catalyzed vapor-solid-solid growth. Specifically, PdIn
      catalyst particles are involved and found to expose their PdIn{210} planes at the
      InP nucleation frontier due to their minimal lattice mismatch with nonpolar
      InP{2110} and {1100} planes. This appropriate lattice registration would then
      minimize the overall free energy and enable the highly crystalline InP NW growth
      epitaxially along the nonpolar directions. Because of the minimized crystal
      defects, the record-high electron mobility of InP NWs ( i.e., 2000 cm2 V-1 s-1 at
      an electron concentration of 1017 cm-3) results, being close to the theoretical
      limit of their bulk counterparts. Furthermore, once the top-gated device geometry
      is employed, the device subthreshold slopes can be impressively reduced down to
      91 mV dec-1 at room temperature. In addition, these NWs exhibit a high
      photoresponsivity of 104 A W-1 with fast rise and decay times of 0.89 and 0.82 s,
      respectively, in photodetection. All these results evidently demonstrate the
      promise of nonpolar-oriented InP NWs for next-generation electronics and
      optoelectronics.

PMID- 30285418
TI  - Surface Fouling of Ultrananocrystalline Diamond Microelectrodes during Dopamine
      Detection: Improving Lifetime via Electrochemical Cycling.
AB  - In this work, we report the electrochemical response of a boron-doped
      ultrananocrystalline diamond (BDUNCD) microelectrode during long-term dopamine
      (DA) detection. Specifically, changes to its electrochemical activity and
      electroactive area due to DA byproducts and surface oxidation are studied via
      scanning electron microscopy, energy dispersive spectroscopy, electrochemical
      impedance spectroscopy, and silver deposition imaging (SDI). The fouling studies
      with amperometry (AM) and fast scan cyclic voltammetry (FSCV) methods suggest
      that the microelectrodes are heavily fouled due to poor DA-dopamine- o-quinone
      cyclization rates followed by a combination of polymer formation and major
      changes in their surface chemistry. SDI data confirms the presence of the
      insulating polymer with sparsely distributed tiny electroactive regions. This
      resulted in severely distorted DA signals and a 90% loss in signal starting as
      early as 3 h for AM and a 56% loss at 6.5 h for FSCV. This underscores the need
      for cleaning of the fouled microelectrodes if they have to be used long-term. Out
      of the three in vivo suitable electrochemical cycling cleaning waveforms
      investigated, the standard waveform (-0.4 V to +1.0 V) provides the best cleaned
      surface with a fully retained voltammogram shape, no hysteresis, no DA signal
      loss (a 90 +/- 0.72 nA increase), and the smallest charge transfer resistance
      value of 0.4 +/- 0.02 MOmega even after 6.5 h of monitoring. Most importantly,
      this is the same waveform that is widely used for in vivo detection with carbon
      fiber microelectrodes. Future work to test these microelectrodes for more than 24
      h of DA detection is anticipated.

PMID- 30285419
TI  - Manipulation of Glutathione-Mediated Degradation of Thiol-Maleimide Conjugates.
AB  - The retro Michael-type addition and thiol exchange of thioether succinimide click
      linkages in response to thiol-containing environments offers a novel strategy for
      the design of glutathione-sensitive degradable hydrogels for controlled drug
      delivery. Here we characterize the kinetics and extent of the retro Michael-type
      addition and thiol exchange with changes in both the p Ka of the thiols and the
      identity of N-substituents of maleimides. A series of N-substituted thioether
      succinimides were prepared through typical Michael-type addition. Model studies
      (1H NMR, HPLC) of 4-mercaptophenylacetic acid (MPA, p Ka 6.6) conjugated to N
      ethyl maleimide (NEM), N-phenyl maleimide (NPM), or N-aminoethyl maleimide (NAEM)
      and then incubated with glutathione showed half-lives of conversion from 3.1 to
      18 h, with extents of conversion from approximately 12% to 90%. The variations in
      the rates of exchange and hydrolytic ring opening appear to be mediated by
      resonance effects, electron-withdrawing capacity of the N-substituted moiety, as
      well as the potential for intramolecular catalytic hydrogen bonding of amine
      substituents with water (particularly in the case of ring opening). Further model
      studies of 4-mercaptohydrocinnamic acid (MPP, p Ka 7.0) and N-acetyl-l-cysteine
      (NAC, p Ka 9.5) conjugated to selected N-substituted maleimides and then
      incubated with glutathione showed half-lives of conversion from 3.6 to 258 h,
      with extents of conversion from approximately 1% to 90%. A higher p Ka of the
      thiol decreased the rate of the exchange reaction and limited the impact of other
      electronic effects of N-substituents on the extents of conversion. Additional
      factors affecting the conversion kinetics were studied on NEM conjugates. The
      kinetics of the retro Michael-type addition and exchange reaction were not
      hindered by thiol traps of lower p Ka, but were retarded in conditions of lower
      pH. These studies shed light into details of thiol and maleimide design that
      could be used to tune the rates of degradation of drug and polymer conjugates for
      a variety of applications.

PMID- 30285420
TI  - Effect of the Processing Route on the Thermoelectric Performance of
      Nanostructured CuPb18SbTe20.
AB  - The quaternary AgPb18SbTe20 compound (abbreviated as LAST) is a prominent
      thermoelectric material with good performance. Endotaxially embedded nanoscale Ag
      rich precipitates contribute significantly to decreased lattice thermal
      conductivity (kappalatt) in LAST alloys. In this work, Ag in LAST alloys was
      completely replaced by the more economically available Cu. Herein, we
      conscientiously investigated the different routes of synthesizing CuPb18SbTe20
      after vacuum-sealed-tube melt processing, including (i) slow cooling of the melt,
      (ii) quenching and annealing, and consolidation by (iii) spark plasma sintering
      (SPS) and also (iv) by the state-of-the-art flash SPS. Irrespective of the method
      of synthesis, the electrical (sigma) and thermal (kappatot) conductivities of the
      CuPb18SbTe20 samples were akin to those of LAST alloys. Both the flash-SPSed and
      slow-cooled CuPb18SbTe20 samples with nanoscale dislocations and Cu-rich
      nanoprecipitates exhibited an ultralow kappalatt ~ 0.58 W/m.K at 723 K,
      comparable with that of its Ag counterpart, regardless of the differences in the
      size of the precipitates, type of precipitate-matrix interfaces, and other
      nanoscopic architectures. The sample processed by flash SPS manifested higher
      figure of merit ( zT ~ 0.9 at 723 K) because of better optimization and a trade
      off between the transport properties by decreasing the carrier concentration and
      kappalatt without degrading the carrier mobility. In spite of their comparable
      sigma and kappatot, zT of the Cu samples is low compared to that of the Ag
      samples because of their contrasting thermopower values. First-principles
      calculations attribute this variation in the Seebeck coefficient to dwindling of
      the energy gap (from 0.1 to 0.02 eV) between the valence and conduction bands in
      MPb18SbTe20 (M = Cu or Ag) when Cu replaces Ag.

PMID- 30285421
TI  - Global Pattern of Microplastics (MPs) in Commercial Food-Grade Salts: Sea Salt as
      an Indicator of Seawater MP Pollution.
AB  - Previous studies have identified microplastics (MPs) in commercial table salts
      but could not exactly address the origin of the MPs because of several
      limitations. The present study is based on the hypothesis that commercial sea
      salts can act as an indicator of MP pollution in the surrounding environment
      unless the MPs are filtered out during the manufacturing process. A total of 39
      different salt brands produced at geospatially different sites, including 28 sea
      salt brands from 16 countries/regions on six continents, were investigated. A
      wide range of MP content (in number of MPs per kg of salt; n/kg) was found: 0
      1674 n/kg (excluding one outlier of 13 629 n/kg) in sea salts, 0-148 n/kg in rock
      salt, and 28-462 n/kg in lake salt. Relatively high MP content was identified in
      sea salts produced in Asian countries/regions. The abundance of MPs in unrefined
      sea salts ( n = 25) exhibited significant linear correlations with plastic
      emissions from worldwide rivers ( r2= 0.33; p = 0.003) and with the MP pollution
      levels in surrounding seawater ( r2= 0.46; p = 0.021) in the published
      literature. The results indicate that not only is Asia a hot spot of global
      plastic pollution, as previous studies have suggested, but also that sea salt can
      be a good indicator of the magnitude of MP pollution in the surrounding marine
      environment.

PMID- 30285422
TI  - Hetero-Bimetallic Effect as a Route to Access Multinuclear Complexes.
AB  - We report the synthesis of a key mononuclear intermediate complex based on a
      quinoid ligand and its further metalation to afford the corresponding hetero
      bimetallic compound that revealed unique properties. An unprecedented hetero
      bimetallic effect in coordination chemistry could be indeed observed and
      exploited to prepare, through selective ligand exchange, a tetranuclear complex
      (Pd-Ni-Ni-Pd) absorbing light up to the far-red region. Most importantly, we
      describe here to the best of our knowledge the first use of bischelating ligand
      for ligand exchange, and this approach can be considered as a new route for
      incorporating planar units to access multi-heteronuclear complexes. The origin of
      this specific ligand exchange as well as of the nature of the electronic excited
      states of the relevant structures were investigated by first-principle
      calculations.

PMID- 30285423
TI  - Relaxing Constrained Amplitudes: Improved F12 Treatments of Orbital Optimization
      and Core-Valence Correlation Energies.
AB  - We present a Lagrangian correction for the energy change upon releasing
      constraints imposed on coupled cluster amplitudes. We demonstrate that our
      correction (i) eliminates the systematic basis set error of the posthoc F12
      treatment in orbital optimized methods and (ii) can be used to relax the F12
      amplitudes and significantly reduce the sensitivity of the core-valence
      correlation energies to the exponent of the correlation factor, while retaining
      the low cost of the fixed amplitude approach.

PMID- 30285424
TI  - Optimal Binding of Acetylene to a Nitro-Decorated Metal-Organic Framework.
AB  - We report the first example of crystallographic observation of acetylene binding
      to -NO2 groups in a metal-organic framework (MOF). Functionalization of MFM-102
      with -NO2 groups on phenyl groups leads to a 15% reduction in BET surface area in
      MFM-102-NO2. However, this is coupled to a 28% increase in acetylene adsorption
      to 192 cm3 g-1 at 298 K and 1 bar, comparable to other leading porous materials.
      Neutron diffraction and inelastic scattering experiments reveal the role of -NO2
      groups, in cooperation with open metal sites, in the binding of acetylene in MFM
      102-NO2.

PMID- 30285426
TI  - Machine Learning Configuration Interaction.
AB  - We propose the concept of machine learning configuration interaction (MLCI)
      whereby an artificial neural network is trained on-the-fly to predict important
      new configurations in an iterative selected configuration interaction procedure.
      We demonstrate that the neural network can discriminate between important and
      unimportant configurations, that it has not been trained on, much better than by
      chance. MLCI is then used to find compact wave functions for carbon monoxide at
      both stretched and equilibrium geometries. We also consider the multireference
      problem of the water molecule with elongated bonds. Results are contrasted with
      those from other ways of selecting configurations: first-order perturbation,
      random selection, and Monte Carlo configuration interaction. Compared with these
      other serial calculations, this prototype MLCI is competitive in its accuracy,
      converges in significantly fewer iterations than the stochastic approaches, and
      requires less time for the higher-accuracy computations.

PMID- 30285425
TI  - Endocannabinoid Virodhamine Is an Endogenous Inhibitor of Human Cardiovascular
      CYP2J2 Epoxygenase.
AB  - The human body contains endogenous cannabinoids (endocannabinoids) that elicit
      effects similar to those of Delta9-tetrahydrocanabinol, the principal bioactive
      component of cannabis. The endocannabinoid virodhamine (O-AEA) is the
      constitutional isomer of the well-characterized cardioprotective and anti
      inflammatory endocannabinoid anandamide (AEA). The chemical structures of O-AEA
      and AEA contain arachidonic acid (AA) and ethanolamine; however, AA in O-AEA is
      connected to ethanolamine via an ester linkage, whereas AA in AEA is connected
      through an amide linkage. O-AEA is involved in regulating blood pressure and
      cardiovascular function. We show that O-AEA is found at levels 9.6-fold higher
      than that of AEA in porcine left ventricle. On a separate note, the cytochrome
      P450 (CYP) epoxygenase CYP2J2 is the most abundant CYP in the heart where it
      catalyzes the metabolism of AA and AA-derived eCBs to bioactive epoxides that are
      involved in diverse cardiovascular functions. Herein, using competitive binding
      studies, kinetic metabolism measurements, molecular dynamics, and wound healing
      assays, we have shown that O-AEA is an endogenous inhibitor of CYP2J2
      epoxygenase. As a result, the role of O-AEA as an endogenous eCB inhibitor of
      CYP2J2 may provide a new mode of regulation to control the activity of
      cardiovascular CYP2J2 in vivo and suggests a potential cross-talk between the
      cardiovascular endocannabinoids and the cytochrome P450 system.

PMID- 30285427
TI  - Urine Metabolic Signatures of Multiple Environmental Pollutants in Pregnant
      Women: An Exposome Approach.
AB  - Exposure to environmental pollutants, particularly during pregnancy, can have
      adverse consequences on child development but little is known about the effects
      of pollutant mixtures on endogenous metabolism in pregnant women. We aimed to
      identify urinary metabolic signatures associated with low level exposure to
      multiple environmental pollutants in pregnant women from the INMA (INfancia y
      Medio Ambiente) birth cohort (Spain, N = 750). 35 chemical exposures were
      quantified in first trimester blood samples (organochlorine pesticides, PCBs,
      PFAS), in cord blood (mercury), and twice in urine at 12 and 32 weeks of
      pregnancy (metals, phthalates, bisphenol A). 1H nuclear magnetic resonance (NMR)
      metabolic profiles of urine were acquired in the same samples as pollutants. We
      explored associations between exposures and metabolism through an exposome
      metabolome wide association scan and multivariate O2PLS modeling. Novel and
      reproducible associations were found across two periods of pregnancy for three
      nonpersistent pollutants and across two subcohorts for four of the persistent
      pollutants. We found novel metabolic signatures associated with arsenic exposure:
      TMAO and dimethylamine possibly related to gut microbial methylamine metabolism
      and homarine related to fish intake. Tobacco smoke exposure was related to coffee
      metabolism and PCBs with 3-hydroxyvaleric acid, usually released under
      ketoacidosis. These findings will have implications for further understanding of
      maternal-fetal health, and health across the life-course.

PMID- 30285428
TI  - [PtZn2Ge18(Hyp)8] (Hyp = Si(SiMe3)3): A Neutral Polynuclear Chain Compound with
      Ge9(Hyp)3 Units.
AB  - The reaction of [ZnGe18(Hyp)6] (Hyp = Si(SiMe3)3) with Pt(PPh3)4 gives the
      neutral polynuclear complex of Ge9(Hyp)3 units [HypZn-Ge9(Hyp)3-Pt-Ge9(Hyp)3
      ZnHyp], 1. Within 1, the central Pt atom is bound eta3 to both Ge9(Hyp)3 units to
      which further ZnHyp units are bound again, symmetric eta3, to the other side of
      the Ge9(Hyp)3 units, leading to the longest chain compound exhibiting Ge9(Hyp)3
      units that is known to date. Dissolved crystals of 1 give a violet solution,
      showing an absorption maximum around 543 nm. Further UV-vis investigations on
      different M xGe9(Hyp)3 compounds show that the absorption maximum depends on the
      number of transition metal atoms bound to the Ge9(Hyp)3 unit, which is supported
      by TD-DFT calculations.

PMID- 30285429
TI  - Toward Engineering Chiral Rodlike Metal-Organic Frameworks with Rare Topologies.
AB  - The establishment of novel design strategies to target chiral rodlike MOFs,
      elusively faced until now, is one of the most straightforward manners to widen
      the scope of MOFs. Here we describe our last advances on the application of the
      metalloligand design strategy toward the development of efficient routes to
      obtain chiral rodlike MOFs. To this end, we have used as precursor an enantiopure
      homochiral hexanuclear wheel (1), derived from the amino acid d-valine, which,
      after a supramolecular reorganization into a one-dimensional homochiral chain
      with the same configuration as 1-led to the formation of a homochiral rodlike MOF
      (2) exhibiting rare etd topology.

PMID- 30285430
TI  - Autoluminescent Metal-Organic Frameworks (MOFs): Self-Photoemission of a Highly
      Stable Thorium MOF.
AB  - A novel thorium(IV) metal-organic framework (MOF), Th(2,6
      naphtalenedicarboxylate)2, has been synthesized via solvothermal reaction of
      thorium nitrate and 2,6-naphtalendicarboxilyc acid. This compound shows a new
      structural arrangement with an interesting topology and an excellent thermal
      resistance, as the framework is stable in air up to 450  degrees C. Most notably,
      this MOF, combining the radioactivity of its metal center and the scintillation
      property of the ligand, has been proven capable of spontaneous photon emission.

PMID- 30285431
TI  - Covalent Organic Framework as Fiber Coating for Solid-Phase Microextraction of
      Chlorophenols Followed by Quantification with Gas Chromatography-Mass
      Spectrometry.
AB  - Headspace solid-phase microextraction coupled with gas chromatography-mass
      spectrometry was adopted for the simultaneous determination of seven
      chlorophenols (CPs) from honey and canned-yellow-peach samples. A covalent
      organic framework made of 1,3,5-triformylphloroglucinol (Tp) and benzidine (BD)
      was used as the SPME fiber coating to preconcentrate the acetylation derivatives
      of the CPs. The main experimental parameters including derivatization conditions,
      extraction temperature and time, headspace volume, salt concentration, and
      desorption temperature were investigated. The fiber showed a high extraction
      capability for the CPs. The limits of detection (LODs) for the analytes were 0.3
      0.7 MUg kg-1 for honey and 0.8-1.8 MUg kg-1 for canned-yellow-peach samples,
      suggesting good sensitivity for the method. The response linearity was 2.4-250
      MUg kg-1 for 2-CP and 3,4-CP and 1.0-150 MUg kg-1 for the other remaining
      analytes in the honey samples. For the canned-yellow-peach samples, the response
      linearity was 6.0-300 MUg kg-1 for 2-CP and 3,4-CP and 3.0-200 MUg kg-1 for the
      others. The correlation coefficients were higher than 0.9919. Good repeatability
      (RSD < 11.9%) for the method and high recoveries (70.2-113%) of the analytes were
      observed under the optimal conditions. The established method was satisfactorily
      applied for the analysis of honey and canned-yellow-peach samples.

PMID- 30285432
TI  - A Microbore Tubing Based Spiral for Multistep Cell Fractionation.
AB  - Cells were separated with the aid of a multistep spiral fractionation device,
      utilizing hydrodynamic forces in a spiral tubing. The spiral was fabricated using
      "off-the-shelf" microbore tubing, allowing for cheap and fast prototyping to
      achieve optimal cell separation. As a first step, a model system with 20 and 40
      MUm beads was used to demonstrate the effectiveness of the multistep separation
      device. With an initial purity of 5%, a separation purity of 83% was achieved
      after a two-step separation with the addition of 0.1% polyethylene glycol (PEG)
      8000. Next, doxorubicin-resistant polyploid giant breast cancer cells (MDA-MB
      231) were separated from doxorubicin-sensitive monoploid small breast cancer
      cells in the same fashion as the beads, resulting in a purity of around 40%,
      while maintaining a cell viability of more than 90%. Combined with basic cell
      analytical methods, the hydrodynamic separation principle of the device could be
      envisaged to be useful for a variety of cell fractionation needs in cell biology
      and in clinical applications.

PMID- 30285433
TI  - Mitigation options of atmospheric Hg emissions in China.
AB  - As the Minamata Convention on Mercury comes into effect, controlling atmospheric
      mercury (Hg) emissions has become a compulsory goal. This study determined the
      mitigation options for the five Convention specified sources by considering their
      reduction potential of Hg emissions and the impact of future technology changes
      on emitted Hg forms and cross-media releases. Hg emissions will be reduced from
      371 t in 2015 to 242 t in 2020 mainly by applying multipollutant control
      measures. Hg emissions will be reduced to 71 t in 2030 mainly with alternative
      measures and specific Hg removal measures (SMR). Alternative measures are
      effective for the studied sources except waste incineration (WI). SMR is
      preferentially recommended in cement clinker production (CEM) due to the benefit
      of sectoral emissions and local deposition. Stringent requirements of Hg emission
      control will promote the use of SMR in WI. In case of nonferrous metal smelting
      (NFMS), only 8.7 t of Hg emissions will be reduced by SMR. However, the co
      benefit of Hg reduction in sulfuric acid and local deposition will increase the
      relevance. On the contrary, applying SMR in coal-fired power plants (CFPPs) and
      coal-fired industrial boilers (CFIBs) requires comprehensive evaluation in terms
      of cost benefit and cross-media effect.

PMID- 30285434
TI  - Hydrothermal Preparation of Five Rare-Earth (Re = Dy, Gd, Ho, Pr, and Sm)
      Luminescent Cluster-Based Coordination Materials: The First MOFs-based
      Ratiometric Fluorescent Sensor for Lysine and Bifunctional Sensing Platform for
      Insulin and Al3.
AB  - Through the powerful hydrothermal method, five rare-earth (Re = Dy, Gd, Ho, Pr,
      and Sm) three-dimensional (3D) cluster-based metal-organic frameworks (MOFs) have
      been synthesized, namely, [Dy(L)(H2O)(DMF)] n (1), {[Gd(L)(H2O)(DMF)].DMF} n (2),
      {[Ho(L)(H2O)(DMF)].0.5DMF} n (3), {[Pr(L)(H2O)(DMF)].0.5DMF} n (4), and
      {[Sm(L)(H2O)1.55(DMF)0.45].DMF} n (5; H3L = terphenyl-3,4",5-tricarboxylic acid),
      which have been determined by single crystal X-ray analyses and PXRD
      characterization. Structural analyses reveal that, in 1-5, these L3- ligands are
      linked by five different rare-earth centers, forming the iso-structural
      nanoporous frameworks. PXRD patterns of bulky samples 1-5 also are consistent
      with theoretical PXRD patterns confirming their purity. Solid state
      photoluminesce of free H3L and 1-5 at room temperature also has been investigated
      indicating strong ligand-based emissions. Besides these, fluorescent dye
      Rhodamine B (RhB) can be introduced into MOF1 forming the composite material
      RhB@MOF1 with a high quantum yield of 35%. It is noted that, through deliberately
      tuning the morphologies of nanoparticle MOF1 under different ultrasonic
      conditions, RhB@MOF1 can be utilized as the first ratiometric fluorescent sensor
      to effectively discriminate l- and d-lysine from other amino acid molecules with
      high Ksv values and low LOD values. On the other hand, 2 was for the first time
      to be utilized as an excellent bifunctional MOFs-based sensing platform to detect
      insulin and Al3+ with a low detection limit in the human serum solution.

PMID- 30285436
TI  - Size Stability Study of Catalytically Active Sub-2 nm Diameter Gold Nanoparticles
      Synthesized with Weak Stabilizers.
AB  - Here we report on the very low size stability of electrocatalytically active 1.5
      to 2.0 nm diameter tetrakis(hydroxymethyl)phosphonium chloride-stabilized Au
      nanoparticles (THPC Au2nm NPs) chemically attached to glass/indium tin oxide
      electrodes. The potential for oxidative dissolution of THPC Au2nm NPs in the
      presence of bromide is about 250 mV negative of 4 nm diameter citrate-stabilized
      Au NPs (Cit Au4nm NPs) and 450 mV negative of bulk Au, which provides us with an
      easy method to assess the size stability using anodic stripping voltammetry. The
      THPC Au2nm NPs show a strong CO2 reduction wave at about -0.40 V (vs RHE), which
      is nonexistent for the Cit Au4nm NPs or bulk Au. The THPC Au2nm NPs are also
      comparatively more electroactive for the hydrogen evolution reaction. In acid
      electrolyte, however, the potential for surface Au2O3 formation on THPC Au2nm NPs
      is significantly negative relative to bulk Au, and a single cycle through the
      surface oxide and reduction waves leads to an increase in the NP size to about 4
      nm. Similarly, the THPC Au2nm NPs undergo Ostwald ripening in the presence of
      bromide within 5 min at potentials well before oxidation, which increases their
      size to 4-10 nm in diameter by 35 min. Exposure to ozone for only 1-2 min also
      causes the THPC Au2nm NPs to increase in size to about 4 nm. In comparison, Cit
      Au4nm NPs are stable under all of these conditions, requiring much longer times
      to change in size. These differences in reactivity and size stability are due to
      the different Au NP size. Sub-2 nm diameter NPs with weak stabilizers are
      potentially very useful for electrocatalysis, but their low oxidation potential
      and poor size stability are major issues of concern.

PMID- 30285435
TI  - Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors.
AB  - Reversible glycosylation of nuclear and cytoplasmic proteins is an important
      regulatory mechanism across metazoans. One enzyme, O-linked N-acetylglucosamine
      transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and
      there is a well-known need for potent, cell-permeable inhibitors to interrogate
      OGT function. Here we report the structure-based evolution of OGT inhibitors
      culminating in compounds with low nanomolar inhibitory potency and on-target
      cellular activity. In addition to disclosing useful OGT inhibitors, the
      structures we report provide insight into how to inhibit glycosyltransferases, a
      family of enzymes that has been notoriously refractory to inhibitor development.

PMID- 30285437
TI  - Enhanced Oxygen Evolution Reaction for Single Atomic Co Catalyst via Support
      Modification: A Density Functional Theory Design Predication.
AB  - Design and development of a single atomic catalyst with high activity is
      desirable but proved to be very challenging in the renewable energy conversion
      and storage technologies. As a classic carbon material, graphene has many
      excellent properties and thus may be a good support to stabilize the isolated
      metal atoms. However, the oxygen evolution activity of a single cobalt atom
      supported on graphene is still very low. To improve its performance, support
      modification has been carried out based on a density functional theory framework
      for the design predication. In our theoretical study, two nitrogen formats are
      incorporated to the graphene substrates, including graphitic nitrogen and
      pyridine-like nitrogen, which are usually observed in experiment. The oxygen
      evolution process has been envisaged on these single cobalt atom catalysts via
      gas phase adsorption calculation. The electronic structure on the single Co
      active site can be effectively regulated by the support modification, which will
      contribute to its enhanced performance. Henceforth, free energy change diagrams,
      partial density of states, Raman spectra, and charge density difference are
      discussed. It is suggested that incorporating pyridine-like nitrogen on graphene
      is an ideal approach for the supported Co atom to achieve high OER activity,
      opening up new opportunity for the preparation and application of highly active
      and stable single atomic catalysts.

PMID- 30285438
TI  - Protonation of a Cobalt Phenylazopyridine Complex at the Ligand Yields a Proton,
      Hydride, and Hydrogen Atom Transfer Reagent.
AB  - Protonation of the Co(I) phenylazopyridine (azpy) complex [CpCo(azpy)] 2 occurs
      at the azo nitrogen of the 2-phenylazopyridine ligand to generate the cationic
      Co(I) complex [CpCo(azpyH)]+ 3 with no change in oxidation state at Co. The N-H
      bond of 3 exhibits diverse hydrogen transfer reactivity, as studies with a
      variety of organic acceptors demonstrate that 3 can act as a proton, hydrogen
      atom, and hydride donor. The thermodynamics of all three cleavage modes for the N
      H bond (i.e., proton, hydride, and hydrogen atom) were examined both
      experimentally and computationally. The N-H bond of 3 exhibits a p Ka of 12.1, a
      hydricity of Delta G degrees H- = 89 kcal/mol, and a bond dissociation free
      energy (BDFE) of Delta G degrees H* = 68 kcal/mol in CD3CN. Hydride transfer from
      3 to the trityl cation (Delta G degrees H- = 99 kcal/mol) is exergonic but takes
      several hours to reach completion, indicating that 3 is a relatively poor hydride
      donor, both kinetically and thermodynamically. Hydrogen atom transfer from 3 to
      2,6-di- tert-butyl-4-(4'-nitrophenyl)phenoxyl radical (tBu2NPArO., Delta G
      degrees H* = 77.8 kca/mol) occurs rapidly, illustrating the competence of 3 as a
      hydrogen atom donor.

PMID- 30285439
TI  - Visible Light-Induced Aerobic Epoxidation of alpha,beta-Unsaturated Ketones
      Mediated by Amidines.
AB  - An aerobic photoepoxidation of alpha,beta-unsaturated ketones driven by visible
      light in the presence of tetramethylguanidine (3b), tetraphenylporphine (H2TPP),
      and molecular oxygen under mild conditions was revealed. The corresponding
      alpha,beta-epoxy ketones were obtained in yields of up to 94% in 96 h. The
      reaction time was shortened to 4.6 h by flow synthesis. The mechanism related to
      singlet oxygen was supported by experiments and density functional theory (DFT)
      calculations.

PMID- 30285440
TI  - Dynamics of Quaternary Structure Transitions in R-State Carbonmonoxyhemoglobin
      Unveiled in Time-Resolved X-ray Scattering Patterns Following a Temperature Jump.
AB  - It is well-known that tetrameric hemoglobin binds ligands cooperatively by
      undergoing a ligand-induced T -> R quaternary structure transition, a structure
      function relationship that has long served as a model system for understanding
      allostery in proteins. However, kinetic studies of the reverse, R -> T quaternary
      structure transition following photolysis of carbonmonoxyhemoglobin (HbCO) reveal
      complex behavior that may be better explained by the presence of two different R
      quaternary structures coexisting in thermal equilibrium. Indeed, we report here
      time-resolved small- and wide-angle X-ray scattering (SAXS/WAXS) patterns of HbCO
      following a temperature jump that not only provide unambiguous evidence for more
      than one R state, but also unveil the time scale for interconversion between
      them. Since the time scale for the photolysis-induced R -> T transition is likely
      different for different R-states, this structural heterogeneity must be accounted
      for to properly explain the kinetic heterogeneity observed in time-resolved
      spectroscopic studies following photolysis of HbCO.

PMID- 30285441
TI  - Comparative Perturbation Effects Exerted by the Influenza A M2 WT Protein
      Inhibitors Amantadine and the Spiro[pyrrolidine-2,2'-adamantane] Variant AK13 to
      Membrane Bilayers Studied Using Biophysical Experiments and Molecular Dynamics
      Simulations.
AB  - Aminoadamantane drugs are lipophilic amines that block the membrane-embedded
      influenza A M2 WT (wild type) ion channel protein. The comparative effects of
      amantadine ( Amt) and its synthetic spiro[pyrrolidine-2,2'-adamantane] (AK13)
      analogue in dimyristoylphosphatidylcholine (DMPC) bilayers were studied using a
      combination of experimental biophysical methods, differential scanning
      calorimetry (DSC), X-ray diffraction, solid-state NMR (ssNMR) spectroscopy, and
      molecular dynamics (MD) simulations. All three experimental methods pointed out
      that the two analogues perturbed drastically the DMPC bilayers with AK13 to be
      more effective at high concentrations. AK13 was tolerated in lipid bilayers at
      very high concentrations, while Amt was crystallized. This is an important
      consideration in the formulations of drugs as it designates a limitation of Amt
      incorporation. MD simulations verify provided details about the strong
      interactions of the drugs in the interface region between phosphoglycerol
      backbone and lipophilic segments. The two drugs form hydrogen bonding with both
      water and sn-2 carbonyls in their amine form or water and phosphate oxygens in
      their ammonium form. Such localization of the drugs explains the DMPC bilayers
      reorientation and their strong perturbing effect evidenced by all biophysical
      methodologies applied.

PMID- 30285442
TI  - Revisiting the Formation Mechanism of 1,3,4-Oxadiazole-2(3 H)-ones from
      Hydrazonyl Chloride and Carbon Dioxide.
AB  - The reaction mechanism for the synthesis of 1,3,4-oxadiazole-2(3 H)-ones from
      hydrazonyl chloride and CO2 in the presence of CsF/18-crown-6 and toluene, is
      revisited via density functional theory computations. Although this reaction was
      earlier classified as a 1,3-dipolar cycloaddition, we found some competing
      pathways involved therein. The mechanisms including the (F-CO2)- anion and the
      nitrile imine intermediate are some options. The dimerization of nitrile imine is
      another competing mechanism in this reaction. Our results show that the most
      favorable mechanism proceeds via a stepwise pathway without involving any nitrile
      imine intermediate or the (F-CO2)- anion. The F- anion, resulting from the
      formation of a complex between 18-crown-6 and Cs+ cation, deprotonates the
      nitrile imine precursor easily, which acts then as a nucleophilic anion,
      enhancing the reactivity of CO2 toward it. The mechanism for the reaction with
      COS, an isoelectronic analogue of CO2, is also explored.

PMID- 30285443
TI  - Dispersion Correction Alleviates Dye Stacking of Single-Stranded DNA and RNA in
      Simulations of Single-Molecule Fluorescence Experiments.
AB  - We combine single-molecule Forster resonance energy transfer (single-molecule
      FRET) experiments with extensive all-atom molecular dynamics (MD) simulations
      (>100 MUs) to characterize the conformational ensembles of single-stranded (ss)
      DNA and RNA in solution. From MD simulations with explicit dyes attached to
      single-stranded nucleic acids via flexible linkers, we calculate FRET
      efficiencies and fluorescence anisotropy decays. We find that dispersion
      corrected water models alleviate the problem of overly abundant interactions
      between fluorescent dyes and the aromatic ring systems of nucleobases. To model
      dye motions in a computationally efficient and conformationally exhaustive
      manner, we introduce a dye-conformer library, built from simulations of
      dinucleotides with covalently attached dye molecules. We use this library to
      calculate FRET efficiencies for dT19, dA19, and rA19 simulated without explicit
      labels over a wide range of salt concentrations. For end-labeled homopolymeric
      pyrimidine ssDNA, MD simulations with the parmBSC1 force field capture the
      overall trend in salt-dependence of single-molecule FRET based distance
      measurements. For homopolymeric purine ssRNA and ssDNA, the DESRES and parmBSC1
      force fields, respectively, provide useful starting points, even though our
      comparison also identifies clear deviations from experiment.

PMID- 30285444
TI  - Comparison Study on the Prediction of Multiple Molecular Properties by Various
      Neural Networks.
AB  - Various neural networks, including a single layer neural network (SLNN), a deep
      neural network (DNN) with multilayers, and a convolution neural network (CNN)
      have been developed and investigated to predict multiple molecular properties
      simultaneously. The data set of this work contains~134 kilo molecules and their
      15 properties (including rotational constant A, B, and C, dipole moment,
      isotropic polarizability, energy of HOMO, energy of LUMO, HOMO-LUMO gap energy,
      electronic spatial extent, zero point vibrational energy, internal energy at 0 K,
      internal energy at 298.15 K, enthalpy at 298.15 K, free energy at 298.15 K, and
      heat capacity at 298.15 K) at the hybrid density functional theory (DFT) level
      from the QM9 database. Coulomb matrix (CM) converted from the database
      representing every molecule uniquely and its eigenvalue are respectively used as
      the input of machine learning. The accuracies of predictions have been compared
      among SLNN, DNN and CNN by analyzing their mean absolute errors (MAEs). Using
      eigenvalues as input, both SLNN and DNN can give higher accuracy for the
      prediction of specific energy properties ( U0, U, H, and G). For the prediction
      of all 15 molecular properties at a time, DNN with a 3-layers network exhibits
      the best results using the full CM as input. The number of layers in DNN play a
      key role in the prediction of multiple molecular properties simultaneously. This
      work may provide possibility and guidance for the selection of different neural
      networks and input data forms for prediction and validation of multiple
      parameters according to different needs.

PMID- 30285445
TI  - How the Conformations of an Internal Junction Contribute to Fold an RNA Domain.
AB  - Like proteins, some RNAs fold to compact structures. We can model functional RNAs
      as a series of short, rigid, base-paired elements, connected by non-base-paired
      nucleotides that serve as junctions. These connecting regions bend and twist,
      facilitating the formation of tertiary contacts that stabilize compact states.
      Here, we explore the roles of salt and junction sequence in determining the
      structures of a ubiquitous connector: an asymmetric internal loop. We focus on
      the J5/5a junction from the widely studied P4-P6 domain of the Tetrahymena
      ribozyme. Following the addition of magnesium ions to fold P4-P6, this junction
      bends dramatically, bringing the two halves of the RNA domain together for
      tertiary contact engagement. Using single-molecule fluorescence resonance energy
      transfer (smFRET), we examine the role of sequence and salt on model RNA
      constructs that contain these junction regions. We explore the wild-type J5/5a
      junction as well as two sequence variants. These junctions display distinct, salt
      dependent conformations. Small-angle X-ray scattering (SAXS) measurements verify
      that these effects persist in the full-length P4-P6 domain. These measurements
      underscore the importance of junction sequence and interactions with ions in
      facilitating RNA folding.

PMID- 30285446
TI  - Diameter-Dependent Superconductivity in Individual WS2 Nanotubes.
AB  - Transition metal dichalcogenide nanotubes are fascinating platforms for the
      research of superconductivity due to their unique dimensionalities and
      geometries. Here we report the diameter dependence of superconductivity in
      individual WS2 nanotubes. The superconductivity is realized by electrochemical
      doping via the ionic gating technique in which the diameter of the nanotube is
      estimated from the periodic oscillating magnetoresistance, known as the Little
      Parks effect. The critical temperature of superconductivity displays an
      unexpected linear behavior as a function of the inverse diameter, that is, the
      curvature of the nanotube. The present results are an important step in
      understanding the microscopic mechanism of superconductivity in a nanotube,
      opening up a new way of superconductivity in crystalline nanostructures.

PMID- 30285447
TI  - WS2-Graphite Dual-Ion Batteries.
AB  - A novel WS2-graphite dual-ion battery (DIB) is developed by combining a
      conventional graphite cathode and a high-capacity few-layer WS2-flake anode. The
      WS2 flakes are produced by exploiting wet-jet milling (WJM) exfoliation, which
      allows large-scale and free-material loss production (i.e., volume up to 8 L h-1
      at concentration of 10 g L-1 and exfoliation yield of 100%) of few-layer WS2
      flakes in dispersion. The WS2 anodes enable DIBs, based on hexafluorophosphate
      (PF6-) and lithium (Li+) ions, to achieve charge-specific capacities of 457, 438,
      421, 403, 295, and 169 mAh g-1 at current rates of 0.1, 0.2, 0.3, 0.4, 0.8, and
      1.0 A g-1, respectively, outperforming conventional DIBs. The WS2-based DIBs
      operate in the 0 to 4 V cell voltage range, thus extending the operating voltage
      window of conventional WS2-based Li-ion batteries (LIBs). These results
      demonstrate a new route toward the exploitation of WS2, and possibly other
      transition-metal dichalcogenides, for the development of next-generation energy
      storage devices.

PMID- 30285448
TI  - Origin of Broad Emission Spectra in InP Quantum Dots: Contributions from
      Structural and Electronic Disorder.
AB  - The ensemble emission spectra of colloidal InP quantum dots are broader than
      achievable spectra of cadmium- and lead-based quantum dots, despite similar
      single-particle line widths and significant efforts invested in the improvement
      of synthetic protocols. We seek to explain the origin of persistently broad
      ensemble emission spectra of colloidal InP quantum dots by investigating the
      nature of the electronic states responsible for luminescence. We identify a
      correlation between red-shifted emission spectra and anomalous broadening of the
      excitation spectra of luminescent InP colloids, suggesting a trap-associated
      emission pathway in highly emissive core-shell quantum dots. Time-resolved pump
      probe experiments find that electrons are largely untrapped on photoluminescence
      relevant time scales pointing to emission from recombination of localized holes
      with free electrons. Two-dimensional electronic spectroscopy on InP quantum dots
      reveals multiple emissive states and increased electron-phonon coupling
      associated with hole localization. These localized hole states near the valence
      band edge are hypothesized to arise from incomplete surface passivation and
      structural disorder associated with lattice defects. We confirm the presence and
      effect of lattice disorder by X-ray absorption spectroscopy and Raman scattering
      measurements. Participation of localized electronic states that are associated
      with various classes of lattice defects gives rise to phonon-coupled defect
      related emission. These findings explain the origins of the persistently broad
      emission spectra of colloidal InP quantum dots and suggest future strategies to
      narrow ensemble emission lines comparable to what is observed for cadmium-based
      materials.

PMID- 30285449
TI  - Proteomic Investigation of Murine Neuronal alpha7-Nicotinic Acetylcholine
      Receptor Interacting Proteins.
AB  - The alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) is a ligand-gated ion
      channel that is expressed widely in vertebrates and is the principal high
      affinity alpha-bungarotoxin (alpha-bgtx) binding protein in the mammalian CNS.
      alpha7-nAChRs associate with proteins that can modulate its properties. The
      alpha7-nAChR interactome is the summation of proteins interacting or associating
      with alpha7-nAChRs in a protein complex. To identify an alpha7-nAChR interactome
      in neural tissue, we isolated alpha-bgtx-affinity protein complexes from wild
      type and alpha7-nAChR knockout (alpha7 KO) mouse whole brain tissue homogenates
      using alpha-bgtx-affinity beads. Affinity precipitated proteins were trypsinized
      and analyzed with an Orbitrap Fusion mass spectrometer. Proteins isolated with
      the alpha7-nAChR specific ligand, alpha-bgtx, were determined to be alpha7-nAChR
      associated proteins. The alpha7-nAChR subunit and 120 additional proteins were
      identified. Additionally, 369 proteins were identified as binding to alpha-bgtx
      in the absence of alpha7-nAChR expression, thereby identifying nonspecific
      proteins for alpha7-nAChR investigations using alpha-bgtx enrichment. These
      results expand on our previous investigations of alpha7-nAChR interacting
      proteins using alpha-bgtx-affinity bead isolation by controlling for differences
      between alpha7-nAChR and alpha-bgtx-specific proteins, developing an improved
      protein isolation methodology, and incorporating the latest technology in mass
      spectrometry. The alpha7-nAChR interactome identified in this study includes
      proteins associated with the expression, localization, function, or modulation of
      alpha7-nAChRs, and it provides a foundation for future studies to elucidate how
      these interactions contribute to human disease.

PMID- 30285450
TI  - Skyrmions in the Moire of van der Waals 2D Magnets.
AB  - We explore the skyrmion formation and control possibilities in two-dimensional
      (2D) magnets from the ubiquitous moire pattern in vdW heterostructures. Using the
      example of a ferromagnetic monolayer on an antiferromagnetic substrate, we
      demonstrate a new origin of skyrmions in the 2D magnets from the lateral
      modulation of interlayer magnetic coupling by the locally different atomic
      registries in moire. The moire skyrmions are doubly degenerate with opposite
      topological charge and trapped at an ordered array of sites with the moire
      periodicity that can be dramatically tuned by strain and interlayer translation.
      At relatively strong interlayer coupling, the ground states are skyrmion
      lattices, where magnetic field can switch the skyrmion vorticity and location in
      the moire. At weak interlayer coupling limit, we find metastable skyrmion
      excitations on the ferromagnetic ground state that can be deterministically moved
      between the ordered moire trapping sites by current pulses. Our results point to
      potential uses of moire skyrmions both as information carriers and as drastically
      tunable topological background of electron transport.

PMID- 30285452
TI  - Highlights of the Langmuir 2018 Editorial Advisory Board.

PMID- 30285451
TI  - Crystallization of Poly(ethylene oxide) on the Surface of Aqueous Salt Solutions
      Studied by Grazing Incidence Wide-Angle X-ray Scattering.
AB  - We report the thin layer crystallization of high-molar mass poly(ethylene oxide)
      (PEO) on a liquid support using a 4 M K2CO3 aqueous solution as a subphase.
      Because of the Hofmeister effect, PEO does not dissolve and remains at the
      surface during compression on a Langmuir trough. The transition from the flat
      pancake conformation upon compression of the spread polymer film to an entangled
      monolayer results in a plateau region of the Langmuir isotherm. Using grazing
      incidence wide-angle X-ray scattering, the final crystallization of PEO was
      observed, and the crystal orientation was determined. The fold surface was (209),
      that is, the helix axis has a tilt angle of 2.9 degrees  to the normal vector of
      the water surface.

PMID- 30285453
TI  - Tunable Electron-Injection Channels of Heterostructured ZnSe@CdTe Nanocrystals
      for Surface-Chemistry-Involved Electrochemiluminescence.
AB  - Tunable charge transfer in and out of nanocrystals (NCs) is crucial to their
      profound light-emitting applications. Herein a convenient strategy toward tunable
      electron-injection channels of NCs was achieved by partially coating highly
      passivated CdTe NCs with unperfected ZnSe shell. Potential- and spectrum-resolved
      electrochemiluminescence (ECL) characterizations proved that radiative charge
      recombination for ECL of the heterostructured ZnSe@CdTe NCs only occurred within
      CdTe core, whereas configurational ions in ECL solution could electrostatically
      or chemically change the surface states of both the ZnSe shell and the uncoated
      CdTe core, resulting in tunable electron-injection channels for ECL of ZnSe@CdTe
      NCs. S2- anion postponed the electron-injection channel for ECL of ZnSe@CdTe NCs
      from -1.44 to -1.58 V, Zn2+ cation presented two electron-injection channels for
      ECL at -1.53 and -1.22 V, respectively, whereas Cd2+ cation enabled three
      electron-injection channels for ECL at -1.53, -1.18, and -0.95 V, respectively.
      The "valve"-like role of configurational ions on the electron-injection channels
      of ZnSe@CdTe NCs is promising to design novel electrochemiluminophores.

PMID- 30285454
TI  - Silicon Nanoribbon pH Sensors Protected by a Barrier Membrane with Carbon
      Nanotube Porins.
AB  - Limited biocompatibility and fouling propensity can restrict real-world
      applications of a large variety of biosensors. Biological systems are adept at
      protecting and separating vital components of biological machinery with
      semipermeable membranes that often contain defined pores and gates to restrict
      transmembrane transport only to specific species. Here we use a similar approach
      for creating fouling-resistant pH sensors. We integrate silicon nanoribbon
      transistor sensors with an antifouling lipid bilayer coating that contains proton
      permeable carbon nanotube porin (CNTP) channels and demonstrate robust pH
      detection in a variety of complex biological fluids.

PMID- 30285455
TI  - In Vivo Laser-Mediated Retinal Ganglion Cell Optoporation Using KV1.1 Conjugated
      Gold Nanoparticles.
AB  - Vision loss caused by retinal diseases affects hundreds of millions of
      individuals worldwide. The retina is a delicate central nervous system tissue
      stratified into layers of cells with distinct roles. Currently, there is a void
      in treatments that selectively target diseased retinal cells, and current
      therapeutic paradigms present complications associated with off-target effects.
      Herein, as a proof of concept, we introduce an in vivo method using a femtosecond
      laser to locally optoporate retinal ganglion cells (RGCs) targeted with
      functionalized gold nanoparticles (AuNPs). We provide evidence that AuNPs
      functionalized with an antibody toward the cell-surface voltage-gated K+ channel
      subunit KV1.1 can selectively deliver fluorescently tagged siRNAs or fluorescein
      isothiocyanate-dextran dye into retinal cells when irradiated with an 800 nm 100
      fs laser. Importantly, neither AuNP administration nor irradiation resulted in
      RGC death. This system provides a novel, non-viral-based approach that has the
      potential to selectively target retinal cells in diseased regions while sparing
      healthy areas and may be harnessed in future cell-specific therapies for retinal
      degenerative diseases.

PMID- 30285456
TI  - In Silico Screen and Structural Analysis Identifies Bacterial Kinase Inhibitors
      which Act with beta-Lactams To Inhibit Mycobacterial Growth.
AB  - New tools and concepts are needed to combat antimicrobial resistance.
      Actinomycetes and firmicutes share several eukaryotic-like Ser/Thr kinases (eSTK)
      that offer antibiotic development opportunities, including PknB, an essential
      mycobacterial eSTK. Despite successful development of potent biochemical PknB
      inhibitors by many groups, clinically useful microbiologic activity has been
      elusive. Additionally, PknB kinetics are not fully described, nor are structures
      with specific inhibitors available to inform inhibitor design. We used
      computational modeling with available structural information to identify human
      kinase inhibitors predicted to bind PknB, and we selected hits based on drug-like
      characteristics intended to increase the likelihood of cell entry. The
      computational model suggested a family of inhibitors, the imidazopyridine
      aminofurazans (IPAs), bind PknB with high affinity. We performed an in-depth
      characterization of PknB and found that these inhibitors biochemically inhibit
      PknB, with potency roughly following the predicted models. A novel X-ray
      structure confirmed that the inhibitors bound as predicted and made favorable
      protein contacts with the target. These inhibitors also have antimicrobial
      activity toward mycobacteria and nocardia. We demonstrated that the inhibitors
      are uniquely potentiated by beta-lactams but not antibiotics traditionally used
      to treat mycobacteria, consistent with PknB's role in sensing cell wall stress.
      This is the first demonstration in the phylum actinobacteria that some beta
      lactam antibiotics could be more effective if paired with a PknB inhibitor.
      Collectively, our data show that in silico modeling can be used as a tool to
      discover promising drug leads, and the inhibitors we discovered can act with
      clinically relevant antibiotics to restore their efficacy against bacteria with
      limited treatment options.

PMID- 30285457
TI  - Oxidative Rearrangement of 3-Aminoindazoles for the Construction of 1,2,3
      Benzotriazine-4(3 H)-ones at Ambient Temperature.
AB  - A novel oxidative rearrangement of 3-aminoindazoles is reported, enabling the
      production of diverse functionalized 1,2,3-benzotriazine-4(3 H)-ones in good
      yields at room temperature. The key success of this unprecedented transformation
      of 3-aminoindazoles is the use of water as cosolvent, which could facilitate the
      halogen-induced ring expansion of 3-aminoindazoles under oxidative conditions.

PMID- 30285458
TI  - Controlling the Trajectories of Nano/Micro Particles Using Light-Actuated
      Marangoni Flow.
AB  - The ability to manipulate small objects and to produce patterns on the nano- and
      microscale is of great importance, both with respect to fundamentals and
      technological applications. The manipulation of particles with diameters of the
      order of 100 nm or below is a challenge because of their Brownian motion but also
      because of the scaling behavior of methods such as optical trapping. The
      unification of optical and hydrodynamic forces is a potential route toward the
      manipulation of tiny objects. Herein we demonstrate the trapping and manipulation
      of nano- and microparticles based on interfacial flows controlled by visible
      light, a method we denote as "Light-Actuated Marangoni Tweezer (LAMT)". We
      experimentally study the manipulation of particles having diameters ranging from
      20 nm to 10 MUm, including quantum dots and polystyrene nano/microparticles. The
      particles can be manipulated by scanning a light beam along a liquid surface. In
      this way, we are able to define almost arbitrary particle trajectories, for
      example, in the form of letters. In addition, we are able to handle a number of
      particles in parallel by creating an optical "landscape" consisting of a
      multitude of laser spots. The inherent advantages of LAMTs are the linear scaling
      of the trapping force with the particle diameter and the fact that the force is
      less dependent on particle properties than in the case of conventional methods.

PMID- 30285459
TI  - Advantages of an Attached Semitendinosus Tendon Graft in Anterior Cruciate
      Ligament Reconstruction in a Rabbit Model.
AB  - BACKGROUND:: The semitendinosus tendon graft with an intact tibial insertion has
      a sustainable blood supply and might be beneficial for graft maturation after
      anterior cruciate ligament reconstruction (ACLR); however, its potential
      advantages for graft tendon-bone healing is still unclear. HYPOTHESIS:: Intact
      tibial insertion of the hamstring tendon can preserve enough blood supply to keep
      the harvested tendon alive, which can improve tendon-bone healing and the
      biomechanical strength of the graft. STUDY DESIGN:: Controlled laboratory study.
      METHODS:: Sixty-four healthy New Zealand White rabbits underwent unilateral ACLR
      with a semitendinosus tendon autograft after random enrollment into 2 groups
      (study group, n = 32 rabbits with semitendinosus tendon-preserved tibial
      insertions; control group, n = 32 rabbits with free semitendinosus tendons). At
      weeks 3, 6, 12, and 24, 8 rabbits in each group were sacrificed to evaluate
      tendon-bone healing by histologic staining, micro-computed tomography (micro-CT)
      examination, and biomechanical test. RESULTS:: The grafts in the study group
      maintained a similar cell count with no signs of necrosis or hypocellularity
      across all time points, but the grafts in the control group underwent a
      characteristic stage of necrosis at weeks 3 and 6. Sharpey-like fibers were
      observed from postoperative 3 weeks at the tendon-bone interface in the study
      group, and a normal insertion-like structure was formed at week 12, which became
      more mature at week 24. In the control group, however, Sharpey-like fibers could
      not be observed until week 12, and a normal transition through cartilage from
      bone to tendon was not observed at any time point. Histologic scores of the
      tendon-bone interface in the study group were significantly higher than those in
      the control group at week 6 ( P = .04), week 12 ( P < .001), and week 24 ( P =
      .04). As compared with the control group via micro-CT, the study group had a
      significantly smaller bone tunnel area at week 6 ( P = .01) and larger bone
      volume/total volume at week 3 ( P = .0026) and week 6 ( P = .01). Also, the study
      group had a significantly higher failure load at weeks 12 and 24 (both P = .03)
      and a significantly higher stiffness at week 24 ( P < .001) versus the control
      group. CONCLUSION:: The semitendinosus tendon graft with an intact tibial
      insertion in ACLR would bypass the graft avascular necrosis stage, which improves
      tendon-bone healing and biomechanical strength. CLINICAL RELEVANCE:: An alive
      graft in ACLR could improve tendon-bone healing and the biomechanical strength of
      the graft, which might be beneficial to early and intensive rehabilitation after
      ACLR.

PMID- 30285460
TI  - Double-Layer Rotator Cuff Repair: Anatomic Reconstruction of the Superior Capsule
      and Rotator Cuff Improves Biomechanical Properties in Repairs of Delaminated
      Rotator Cuff Tears.
AB  - BACKGROUND:: Delamination in rotator cuff tears has been identified as a
      prognostic factor for negative outcome after repair, with a reported prevalence
      between 38% and 88%. PURPOSE:: To compare biomechanical properties of 3 repair
      techniques for delaminated rotator cuff tears. STUDY DESIGN:: Controlled
      laboratory study. METHODS:: Eighteen fresh-frozen cadaveric shoulders were used
      to evaluate rotator cuff footprint reconstruction, contact area and pressure,
      displacement under cyclical loading, and load to failure of 3 double-row repair
      configurations: double-row suture repair with medial row knots (medially knotted
      bridge, mkB); knotless double-row repair using suture tapes (knotless bridge,
      klB); and knotless double-row, double-layer-specific repair (double-layer, DL).
      Dynamic pressure sensors were used to assess contact patterns at the footprint
      region in 0 degrees , 30 degrees , and 60 degrees  of glenohumeral abduction and
      5 rotational positions (0 degrees , 30 degrees  of internal rotation, 30 degrees 
      of external rotation, 60 degrees  of internal rotation, 60 degrees  of external
      rotation). Optical markers were used to document whole tendon and individual
      layer displacement after rotator cuff repair under cyclical loading for 200
      cycles (10 N to 100 N at 1 Hz). Specimens were then loaded monotonically to
      failure at a rate of 33 mm/min. RESULTS:: Mean contact area and footprint
      restoration were highest in the DL group at 60 degrees  of glenohumeral abduction
      for all rotational positions (mkB mean +/- SD, 195.4 +/- 54.3 mm2, 66.7% +/-
      19.7%; klB, 250.6 +/- 34.9 mm2, 76.2% +/- 10.3%; DL, 318.4 +/- 36.6 mm2, 109.1%
      +/- 24.0%; P < .001). The double-layer-specific repair showed the least
      displacement under cyclical loading (mkB mean +/- SD, 0.53 +/- 0.18 mm; klB, 0.79
      +/- 0.37 mm; DL, 0.31 +/- 0.24 mm; P = .029), most closely resembling the native
      tendon. Peak loads at failure were comparable between repair groups (mkB mean +/-
      SD, 366.92 +/- 70.59 N; klB, 280.05 +/- 77.66 N; DL, 398.35 +/- 109.04 N; P =
      .083). CONCLUSION:: Anatomic restoration of the superior capsular and tendon
      insertion in delaminated rotator cuff tears with a double-layer-specific repair
      configuration demonstrated superior footprint restoration with increasing
      abduction, while providing construct displacement comparable to the native tendon
      under cyclical loading. Peak load at failure was comparable between repair
      constructs. CLINICAL RELEVANCE:: The prevalence and clinical importance of
      delaminated rotator cuff tears have long been underestimated. Anatomically
      correct individual reconstruction of the superior capsule and rotator cuff could
      restore near-native biomechanics and potentially reduce the risk of rotator cuff
      repair failure.

PMID- 30285461
TI  - Milk-Derived Exosomes and Metabolic Regulation.
AB  - Exosomes are natural nanoparticles that play an important role in cell-to-cell
      communication. Communication is achieved through the transfer of cargos, such as
      microRNAs, from donor to recipient cells and binding of exosomes to cell surface
      receptors. Exosomes and their cargos are also obtained from dietary sources, such
      as milk. Exosome and cell glycoproteins are crucial for intestinal uptake. A
      large fraction of milk exosomes accumulates in the brain, whereas the tissue
      distribution of microRNA cargos varies among distinct species of microRNA. The
      fraction of milk exosomes that escapes absorption elicits changes in microbial
      communities in the gut. Dietary depletion of exosomes and their cargos causes a
      loss of circulating microRNAs and elicits phenotypes such as loss of cognitive
      performance, increase in purine metabolites, loss of fecundity, and changes in
      the immune response. Milk exosomes meet the definition of bioactive food
      compounds. Expected final online publication date for the Annual Review of Animal
      Biosciences Volume 7 is February 15, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30285462
TI  - Hepatitis E Virus: Animal Models and Zoonosis.
AB  - Hepatitis E virus (HEV) is an important human pathogen that historically has been
      difficult to study. Limited levels of replication in vitro hindered our
      understanding of the viral life cycle. Sporadic and low-level virus shedding,
      lack of standardized detection methods, and subclinical infections made the
      development of animal models difficult. Better diagnostic techniques and
      understanding of the virus increased our ability to identify and characterize
      animal strains and animals that are amenable to model human-relevant infection.
      These advances are translating into the development of useful HEV animal models
      so that some of the greatest concerns associated with HEV infection, including
      host immunology, chronic infection, severe pregnancy mortality, and extrahepatic
      manifestations, can now be studied. Continued development of these animal models
      will be instrumental in understanding the many complex questions associated with
      HEV infection and for assessing therapeutics and prevention strategies to
      minimize HEV becoming a greater risk to the human population. Expected final
      online publication date for the Annual Review of Animal Biosciences Volume 7 is
      February 15, 2019. Please see http://www.annualreviews.org/page/journal/pubdates
      for revised estimates.

PMID- 30285463
TI  - Acetabular Labral Reconstruction: Development of a Tool to Predict Outcomes.
AB  - BACKGROUND:: Acetabular labral reconstruction has demonstrated good results for
      labral lesions not amenable to labral repair. PURPOSE:: To determine the
      predictors of outcomes at a minimum 2 years after labral reconstruction. STUDY
      DESIGN:: Case series; Level of evidence, 4. METHODS:: Patients included in the
      study underwent labral reconstruction with a minimum 2-year follow-up. The
      primary outcome variable was the Hip Outcome Score-Activities of Daily Living
      (HOS-ADL). Secondary outcome measures included the 12-item Short Form Health
      Survey physical component summary (SF-12 PCS) and patient satisfaction with
      surgical outcomes. Preoperative and intraoperative variables assessed included
      demographics, prior surgery, chronicity of symptoms, radiographic measurements,
      preoperative outcome scores, and findings at arthroscopic surgery. Predictors
      were assessed using logistic regression with restricted cubic splines. Bivariate
      statistics assessed risk factors for reoperation including revision arthroscopic
      surgery and total hip arthroplasty (THA). RESULTS:: Three hundred seventeen of
      368 labral reconstructions were available for follow-up (86.1%). Of these, 42
      were converted to THA (13.2%) and 35 required revision arthroscopic surgery after
      labral reconstruction (11.0%). Factors associated with THA included older age,
      >=2 previous surgeries, <=2 mm of joint space, and lateral center edge angle
      (LCEA) <25 degrees . Factors associated with revision included female sex, >=2
      previous surgeries, and LCEA <25 degrees . Six patients refused to participate
      (1.9%), leaving 234 with a minimum follow-up of 2 years (mean, 3.7 years [range,
      2.0-11.3 years]). These patients had significant improvement in HOS-ADL (71 to
      90; P < .001), HOS-Sport (47 to 75; P < .001), Western Ontario and McMaster
      Universities Osteoarthritis Index (27 to 9; P < .001), modified Harris Hip Score
      (65 to 85; P < .001), and SF-12 PCS scores (41.6 to 53.1; P < .001). Median
      postoperative satisfaction was 9. Predictors of improvement for the HOS-ADL
      included higher preoperative HOS-ADL scores ( P < .001), joint space >2 mm ( P =
      .004), and no prior surgery ( P = .039). Predictors of improvement for the SF-12
      PCS included higher preoperative SF-12 PCS scores ( P < .001), subacute
      chronicity (3 months to 1 year) of symptoms ( P = .013), and joint space >2 mm (
      P = .046). Joint space >2 mm ( P < .001) and higher preoperative SF-12 scores
      (PCS: P = .034; mental component summary: P = .039) predicted higher
      satisfaction. CONCLUSION:: At a minimum 2 years' follow-up, patients who did not
      undergo conversion to THA (13.2%) or require revision (11.0%), reported
      significant improvement in outcome scores and high satisfaction with outcomes.
      Predictors of revision or THA included >=2 previous surgeries, low LCEA, female
      sex for revision, and narrowed joint space for THA. Higher preoperative outcome
      scores were the most significant predictors of improvement after labral
      reconstruction. Lower preoperative scores, joint space narrowing, and history of
      surgery were predictive of an inferior result and decreased postoperative
      satisfaction.

PMID- 30285464
TI  - Manipulating fenestrations in young and old liver sinusoidal endothelial cells.
AB  - Fenestrations are pores within liver sinusoidal endothelial cells (LSECs) that
      enable the transfer of substrates (particularly insulin and lipoproteins) between
      blood and hepatocytes. With increasing age there are marked reductions in the
      frequency and diameter of fenestrations, referred to as pseudocapillarization.
      Currently, fenestrations are thought to be regulated by VEGF and NO pathways
      promoting remodelling of the actin cytoskeleton and cell membrane lipid rafts. We
      investigated the effects of drugs that act on these pathways on fenestrations in
      old (18-24m) and young mice (3-4m). Isolated LSECs were incubated with either:
      cytochalasin D, 7-ketocholesterol, sildenafil, amlodipine, simvastatin, 2, 5
      dimethoxy-4-iodoamphetamine (DOI), bosentan, TNF-related apoptosis-inducing
      ligand (TRAIL) or nicotinamide mononucleotide (NMN). LSECs were visualized under
      scanning electron microscopy to quantify fenestration porosity, diameter and
      frequency; and direct stochastic optical reconstruction microscopy to examine
      actin and NO synthase. In young and old LSECs, fenestration porosity, diameter
      and frequency were increased by 7-ketocholesterol; while porosity and/or
      frequency were increased with NMN, sildenafil, amlodipine, TRAIL and cytochalasin
      D. In old mice only, bosentan and DOI increased fenestration porosity and/or
      frequency. Modification of the actin cytoskeleton was observed with all agents
      that increased fenestrations, while NO synthase was only increased by sildenafil,
      amlodipine and TRAIL. In conclusion agents that target NO, actin or lipid rafts
      promote changes in fenestrations in mice LSECs. Regulation of fenestrations
      occurs via both NO-dependent and independent pathways. This work indicates that
      age-related defenestration can be reversed pharmacologically which has potential
      translational relevance for dyslipidaemia and insulin resistance.

PMID- 30285465
TI  - SEPIAPTERIN, ALLEVIATES IMPAIRED GASTRIC nNOS FUNCTION IN SPONTANEOUS DIABETIC
      FEMALE RODENTS THROUGH NRF2 mRNA TURNOVER and miRNA BIOGENESIS PATHWAY.
AB  - An impaired nitrergic system and altered redox signaling contribute to gastric
      dysmotility in diabetics. Our earlier studies show that NF-E2-related factor 2
      (NRF2) and Phase II antioxidant enzymes play a vital role in gastric neuronal
      nitric oxide synthase (nNOS) function. This study aims to investigate whether
      supplementation of sepiapterin (SEP), a precursor for BH4 (a cofactor of NOS) via
      salvage pathway, restores altered nitrergic systems and redox balance in
      spontaneous diabetic (DB) female rats. Twelve-week spontaneous DB and age
      matched, non-DB rats, with and without dietary SEP (daily 20 mg/kg body weight
      for 10 days) treatment, were used in this study. Gastric antrum muscular tissues
      were excised to investigate the effects of SEP in nitrergic relaxation and the
      nNOS-NO-NRF2 pathway(s). Dietary SEP supplementation significantly (p<0.05)
      reverted diabetes-induced changes in nNOS dimerization and function; nitric oxide
      (NO) downstream signaling molecules; HSP-90, a key regulator of nNOSalpha
      activity and dimerization; miRNA-28 that targets NRF2 messenger RNA (mRNA) and
      levels of microRNA (miRNA) biogenesis pathway components, such as DGCR8 (DiGeorge
      Syndrome Critical Region Gene 8) and TRBP (HIV1-1 transactivating response [TAR]
      RNA-binding protein). These findings emphasize the importance of the BH4 pathway
      in regulating gastric motility functions in DB animals by modulating nNOSalpha
      dimerization in association with changes in enteric NRF2 and NO downstream
      signaling. Our results also identify a new pathway, wherein SEP regulates NRF2
      mRNA turnover by suppressing elevated miRNA-28, which could be related to
      alterations in miRNA biogenesis pathway components.

PMID- 30285466
TI  - Knockout of ClC-2 reveals critical functions of adherens junctions in colonic
      homeostasis and tumorigenicity.
AB  - BACKGROUND & AIMS: Adherens junctions (AJs), together with tight junctions (TJs),
      form an apical junctional complex that regulates intestinal epithelial cell-to
      cell adherence and barrier homeostasis. Within the AJ, membrane-bound E-cadherin
      binds beta-catenin, which functions as an essential intracellular signaling
      molecule. We have previously identified a novel protein in the region of the
      apical junction complex, chloride channel protein 2 (ClC-2), which we have used
      to study TJ regulation. In this study, we investigated the possible effects of
      ClC-2 on the regulation of AJs in intestinal mucosal epithelial homeostasis and
      tumorigenicity. METHODS: Mucosal homeostasis and junctional proteins were
      examined in wild type (WT) and ClC-2 knockout (KO) mice as well as associated
      colonoids. Tumorigenicity and AJ-associated signaling were evaluated in a murine
      colitis-associated tumor model and in a colorectal cancer cell line (HT-29).
      RESULTS: Colonic tissues from ClC-2 KO mice had altered ultrastructural
      morphology of intercellular junctions with reduced colonocyte differentiation,
      whereas jejunal tissues had minimal changes. Colonic crypts from ClC-2 KO mice
      had significantly higher numbers of less-differentiated forms of colonoids as
      compared to WT. Furthermore, the absence of ClC-2 resulted in redistribution of
      AJ proteins and increased beta-catenin activity. Downregulation of ClC-2 in
      colorectal cells resulted in significant increases in proliferation associated
      with disruption of AJs. Colitis-associated tumors in ClC-2 KO mice were
      significantly increased, associated with beta-catenin transcription factor
      activation. CONCLUSION: The absence of ClC-2 results in less differentiated
      colonic crypts and increased tumorigenicity associated with colitis via
      dysregulation of AJ proteins and activation of beta-catenin-associated signaling.

PMID- 30285467
TI  - Chromatographic Methods for the Determination of Emerging Contaminants in Natural
      Water and Wastewater Samples: A Review.
AB  - This review is devoted to analytical methods published in the scientific
      literature in the last 10 years for the determination of emerging contaminants in
      aquatic media. The article is mainly focused on sample preparation and on
      instrumental techniques most used for the detection and quantification of the
      analytes of interest. The sample preparation techniques include classical liquid
      liquid extraction and solid-phase extraction, but also recent microextraction
      techniques such as solid-phase microextraction, stir-bar sorptive extraction,
      dispersive liquid-liquid microextraction, ultrasound-assisted emulsification
      microextraction, or microextraction by packed sorbent. Most studies focus on
      minimizing the number of analysis steps and on the use of the lowest amount of
      solvents in the sample treatment step. Liquid chromatography and gas
      chromatography mainly coupled to tandem mass spectrometry are usually the
      employed analytical techniques. A large number of multiresidue methods are being
      developed for the determination of several families of these compounds with only
      one extraction step to minimize sample handling and treatment.

PMID- 30285468
TI  - Novel technologies in utilization of byproducts of animal food processing: a
      review.
AB  - China is one of the countries with most abundant livestock and poultry resources
      in the world. The average annual growth rate of output value of livestock and
      poultry industry reaches 13%, and the output value of livestock and poultry
      industry accounts for more than 35% of total agricultural output. A large number
      of byproducts are produced in animal slaughtering and processing operations. If
      livestock and poultry byproducts are effectively utilized, this will make a huge
      contribution to GDP. At the same time, aquaculture is China's pillar industry.
      During fish processing, a large number of byproducts (including fish heads, fish
      skins, fish bones, fish scales, and viscera) are produced, which weighs
      approximately 40-55% of the raw fish. The byproducts of freshwater fish are more
      than 2.5 million tons per annum, most of which are not used. The effective use of
      byproducts has a direct influence on China's economic and environmental
      pollution. The nonuse or underutilization of byproducts not only leads to loss of
      potential revenue, but also results in to an increase in these products and their
      disposal costs. This paper makes a comprehensive review of the research progress
      of animal byproduct utilization to date, and aims to provide reference for the
      utilization and research of animal byproducts.

PMID- 30285469
TI  - Diagnostic ultrasound assessment of temporomandibular joints: a systematic review
      and meta-analysis.
AB  - OBJECTIVES:: The purpose of this systematic review was to determine the
      diagnostic capability of ultrasound to assess TMJ alterations as disc
      displacement (DD), joint effusion (JE) and condylar changes (CC) using 3D imaging
      modalities as reference standard. METHODS:: Studies were gathered by searching
      several electronic databases and partial grey literature up to January eighth,
      2018 without restrictions of language and time. The risk of bias was evaluated
      using the second version of Quality Assessment Tool for Diagnostic of Accuracy
      Studies-2 (QUADAS-2). The grading of Recommendation, Assessment, Development and
      Evaluation (GRADEpro system) instrument was applied to assess the level of
      evidence across the studies. RESULTS:: After applying the eligibility criteria,
      28 studies were identified and synthesized. All studies were methodologically
      acceptable presenting low applicability concerns, although none of them fulfilled
      all QUADAS-2 criteria. The quantitative analysis included 22 studies, 2829 joints
      in total. The quality of the evidence evaluated by GRADE system suggested
      moderate confidence in estimating the outcomes. CONCLUSION:: This systematic
      review demonstrated the ultrasound has acceptable capability to screen for DD and
      JE in TMD patients. For screening of condylar changes, ultrasound needs further
      studies using CT or CBCT as reference standard to support its use. More advanced
      imaging such as MRI can thereafter be used to confirm the diagnosis if deemed
      necessary.

PMID- 30285470
TI  - Chromatographic Methods for Determination of Drugs Used in Prostate Cancer in
      Biological and Pharmacological Samples.
AB  - Prostate cancer is the second most common cancer and the fifth leading cause of
      cancer deaths in men worldwide. This review article contains a summary of
      analyzes performed by chromatographic methods used for the determination of
      abiraterone acetate, bicalutamide, cabazitaxel, docetaxel, enzalutamide,
      flutamide, goserelin acetate, leuprolide acetate, and mitoxantrone hydrochloride
      drugs used in prostate cancer applications in biological and pharmacological
      samples. In this review, sample preparation procedures, chromatographic
      procedures, and detectors used for analytical determinations of these drugs are
      discussed.

PMID- 30285471
TI  - Factors That Modify the Association of Maternal Postpartum Smoking and Exclusive
      Breastfeeding Rates.
AB  - BACKGROUND AND OBJECTIVE: Maternal postpartum smoking increases the risk for poor
      infant health outcomes, while exclusive breastfeeding has been shown to support
      infant health. Limited population-based research has been published on the
      interaction between maternal smoking and exclusive breastfeeding. The objective
      of this study was to examine factors modifying the association between maternal
      postpartum smoking and exclusive breastfeeding among women in the United States.
      METHODS: Secondary data analysis was conducted using the 2009-2011 Pregnancy Risk
      Assessment Monitoring System. Stratified analyses were used to examine the
      associations between maternal postpartum smoking and exclusive breastfeeding by
      sociodemographic factors. RESULTS: The postpartum smoking rate was 17.1%. The
      relationship between postpartum smoking and exclusive breastfeeding at 12 weeks
      varied by maternal education level, race/ethnicity, Medicaid use, and
      pregestational or gestational diabetes. The magnitude of reduction in the odds of
      exclusive breastfeeding at 12 weeks postpartum among the women who smoked in the
      postpartum period ranges from odds ratio (95% confidence interval) 0.52 (0.37
      0.74) for non-Hispanic blacks to 0.31 (0.22-0.43) for women who had <12 years of
      education. CONCLUSIONS: Women who smoked in the postpartum period, who also
      suffered from socioeconomic disadvantages, had a higher likelihood of not
      continuing exclusive breastfeeding. Identification of women at high risk for not
      exclusively breastfeeding is important for targeting populations in need of
      appropriate and timely support for prenatal and postpartum smoking cessation and
      breastfeeding promotion.

PMID- 30285472
TI  - 3D food printing: main components selection by considering rheological
      properties.
AB  - 3D printing, also referred to as additive manufacturing, offers a wide range of
      new processing possibilities to the food industry. This technology allows a layer
      by layer (bottom to top) printing of predefined slices of designed and desired
      objects. 3D printing potentially allows rapid manufacturing of complex objects,
      which are unhindered by design complexity, thus providing substantial liberty to
      create new and untested geometric shapes. In terms of food manufacturing, the
      potential that 3D food printing technologies can bring may revolutionize certain
      aspects of food manufacturing, providing the convenience of low-cost customized
      fabrication and even tailored nutrition control. The most common materials
      suitable for 3D food printing are carbohydrate, fat, protein, fiber and
      functional components. In the present study, the characteristics of raw materials
      or additives used during 3D printing, and requirements for estimating and
      improving their printing performance and self-supporting ability in extrusion
      based printing regarding rheological characteristics of 3D food printing
      materials are reviewed. As an innovative process, 3D food printing may induce a
      revolution in certain areas of food manufacturing.

PMID- 30285474
TI  - Electrochromic Sensors Based on Conducting Polymers, Metal Oxides, and
      Coordination Complexes.
AB  - Electrochromic sensors offer multi-mode registration of analytical signal based
      on combination of electrochemical and optical techniques. This emerging direction
      of analytical chemistry is relatively new; therefore, it has very high potential
      for various applications in chemical and biochemical analysis. Properties of
      sensors based on various electrochromic materials such as polymers, polymer
      derivatives, polymer composites, metal oxides, metal oxide complexes,
      phthalocyanines, porphyrins, and dyes are critically overviewed, evaluated, and
      compared. The most promising directions in analytical application of
      electrochromic polymers are highlighted.

PMID- 30285473
TI  - Methods of extraction, separation, purification, structural characterization for
      polysaccharides from aquatic animals and their major pharmacological activities.
AB  - The further development of fishery resources is a hotspot in the development of
      the fishery industry. However, how to develop aquatic animal resources deeply is
      a key point to be solved in the fishery industry. Over the past decades, numerous
      aquatic animals have gained great attention in the development and utilization of
      their bioactive molecules which are of therapeutic applications as nutraceuticals
      and pharmaceuticals. Recent research revealed that aquatic animals are composed
      of many vital moieties, such as polysaccharides and proteins, which provide
      health benefits beyond basic nutrition. In particular, aquatic animal
      polysaccharides are gaining worldwide popularity owing to their high content,
      ease of extraction, specific structure, few side effects, prominent therapeutic
      potential and incorporation in functional foods and dietary supplements. Thus,
      tremendous research on the isolation, identification and bioactivities of
      polysaccharides has been carried out. This review presents comprehensive
      viewpoints on extraction, separation, purification, structural characterization
      and bioactivity of various polysaccharides from aquatic animals, such as sea
      cucumber, abalone, oyster and mussels. In addition, this review profiled a brief
      knowledge on both current challenges and future scope in aquatic animal
      polysaccharides field. The review will be a direction of deep processing in
      fishery resources, which is a hotspot, but technical bottleneck. Furthermore, the
      review could be served as a useful reference material for further investigation,
      production and application of polysaccharides from aquatic animals in functional
      foods and therapeutic agents.

PMID- 30285475
TI  - Cheesomics: the future pathway to understanding cheese flavour and quality.
AB  - Cheese is a fermented dairy product, harboring diverse microbial communities
      (microbiota) that change over time and vary depending on the type of cheese and
      their respective starter and adjunct cultures. These microorganisms play a
      crucial role in determining the flavor, quality and safety of the final product.
      Exploring the composition of cheese microbiota and the underlying molecular
      mechanisms involved in cheese ripening has been the subject of many studies.
      Recent advances in next generation sequencing (NGS) methods and the development
      of sophisticated bioinformatics tools have provided deeper insights into the
      composition and potential functionality of cheese microbiota far beyond the
      information provided by culture-dependent methods. These advances, which include
      rRNA gene amplicon sequencing and metagenomics, have been complemented and
      expanded in recent years by the application of metatranscriptomics,
      metaproteomics and metabolomics. This paper reviews studies in which application
      of these meta-omics technologies has led to a better understanding of the
      microbial composition and functionality of cheese and highlights opportunities by
      which the integration of outputs from diverse multi-omics analytical platforms
      (cheesomics) could be used in the future to advance our knowledge of the cheese
      ripening process and identify biomarkers for predicting cheese flavor, quality,
      texture and safety, and bioactive metabolites with potential to influence human
      health.

PMID- 30285476
TI  - Excellent Glycemic Control Maintained by Open-Source Hybrid Closed-Loop
      AndroidAPS During and After Sustained Physical Activity.
AB  - OBJECTIVE: Officially licensed hybrid closed-loop systems are not currently
      available worldwide; therefore, open-source systems have become increasingly
      popular. Our aim was to assess the safety, feasibility, and efficacy of an open
      source hybrid closed-loop system (AndroidAPS) versus SmartGuard(r) technology for
      day-and-night glucose control in children under extreme sports conditions.
      RESEARCH DESIGN AND METHODS: Twenty-two children (16 girls, 6-15 years of age,
      median HbA1c 56 +/- 9 mmol/mol) were enrolled in this pivotal winter sports camp
      study. The participants were divided into two groups using either the AndroidAPS
      or SmartGuard technology. Physical exertion was represented by all-day alpine
      skiing. The primary endpoints were mean glucose level, time below the threshold
      of 3.9 mmol/L, and time within the target range of 3.9 to 10 mmol/L. RESULTS: The
      children using the AndroidAPS had significantly lower mean glycemia levels (7.2
      +/- 2.7 vs. 7.7 +/- 2.8 mmol/L; 129.6 +/- 49 vs. 138.6 +/- 50 mg/dL, P < 0.042)
      than the children using the SmartGuard. The proportion of time below the target
      (median 5.0% +/- 2.5% vs. 3.0% +/- 2.3%, P = 0.6) and in the target zone (63% +/-
      9.5% vs. 63% +/- 18%, P = 0.5) did not significantly differ. The AndroidAPS group
      experienced more frequent malfunctions of the cannula set (median 0.8 +/- 0.4 vs.
      0.2 +/- 0.4, P = 0.02), which could have affected the results. No significant
      difference was found in the amount of carbohydrates consumed for the prevention
      and treatment of hypoglycemia [median 40 +/- 23 vs. 25 +/- 29 g/(patient .3
      days)]. No episodes of severe hypoglycemia or other serious adverse events were
      noted. CONCLUSIONS: This pilot study showed that the AndroidAPS system was a safe
      and feasible alternative to the SmartGuard Technology.

PMID- 30285477
TI  - 11th Annual Symposium on Self-Monitoring of Blood Glucose: April 12-14, 2018,
      Oslo, Norway.
AB  - A panel of international experts in the field of diabetes and diabetes technology
      met in Oslo, Norway, for the 11th Annual Symposium on Self-Monitoring of Blood
      Glucose. The goal of these meetings is to share current knowledge, facilitate new
      collaborations, and encourage further research projects that can improve the
      lives of people with diabetes. The 2018 meeting comprised a comprehensive
      scientific program and four keynote lectures.

PMID- 30285478
TI  - Evidence of genotoxicity and cytotoxicity of X-rays in the oral mucosa epithelium
      of adults subjected to cone-beam computed tomography.

PMID- 30285479
TI  - Potentiometry as a Tool for Monitoring of Antioxidant Activity and Oxidative
      Stress Estimation in Medicine.
AB  - The complexity of biological objects and the rapid change in their composition
      after sampling, the variety of compounds of different chemical nature, possessing
      oxidative and antioxidant properties, make the task of its estimating extremely
      nontrivial and important for food, nutrients and human health characterization.
      The paper discusses the use of potentiometry in determining integral
      antioxidant/oxidant activity mainly of biological fluids and human skin. The
      source of information is the electrode potential shift that occurs when the
      analyzed object is inserted in the solution of the mediator system or when the
      mediator system is exposed to human skin. The experimental approaches, protocols,
      calculations are described. A number of examples of antioxidant activity and
      oxidative stress estimation in medicine are presented. The works show lower
      levels of antioxidant activity (AOA) of plasma and blood serum in patients with
      cardiovascular diseases, obesity, and malignant neoplasms as compared with the
      healthy volunteers. It was found out that antioxidant activity of fertile men
      semen is higher than AOA of infertile patients. Using the method discussed have
      shown that in some infertile male patients antioxidant activity of semen has been
      accompanied by oxidant activity. It has been found, that antioxidant activity of
      skin increases after intake of ascorbic acid and vitamin-enriched juices. The
      described approach holds considerable promise for monitoring oxidative stress of
      the whole organism and its systems, and for selecting effective and safe therapy.
      Thus, it opens up new opportunities in expanding the use of analytical chemistry
      in such an important field as medicine.

PMID- 30285480
TI  - Liquid Crystals in Analytical Chemistry: A Review.
AB  - Nearing 130 years since their introduction, liquid crystals (LCs) have found
      diverse applications in different fields of science, including chemical analysis.
      This review encompasses the history of LCs, reviews various types of them, and
      presents their current applications in analytical chemistry. Since most
      applications of LCs in analytical chemistry are for the fabrication of
      biosensors, these applications are discussed first. The high sensitivity of LCs
      to changes in their environment makes them ideal for such sensors. Using them,
      analyte concentrations as low as 1 pM have been detected. Another major
      application of LCs is in gas chromatography (GC) as stationary phases, which is
      described in the second part of this review. Using LCs in GC leads to better
      separations, higher sensitivity, and improved selectivity. Such phases provide
      higher stability in elevated temperatures and increased column life times.
      Finally, applications of LCs in electro-analytical chemistry will be described
      briefly.

PMID- 30285482
TI  - Special issue of selected papers from the 4th European Section Meeting of the
      International Academy of Cardiovascular Sciences held in Pecs, Hungary, on 28-30
      September 2017.

PMID- 30285481
TI  - Enterotoxigenic Escherichia coli (ETEC) heat labile enterotoxin inhibits
      intestinal ascorbic acid uptake via a cAMP-dependent NF-kappaB mediated pathway.
AB  - Vitamin C is an antioxidant and acts as a cofactor for many enzymatic reactions.
      Humans obtain vitamin C from dietary sources via intestinal absorption, a process
      that involves the sodium dependent vitamin C transporters-1 and -2 (SVCT1 and
      SVCT2). Enterotoxigenic Escherichia coli (ETEC) infection impacts intestinal
      absorption/secretory functions but nothing is known about its effect on ascorbic
      acid (AA) uptake. Here we demonstrate that infection of Caco-2 cells with ETEC
      led to a significant inhibition in intestinal AA uptake. This inhibition was
      associated with a marked reduction in hSVCT1 and hSVCT2 protein, mRNA and hnRNA
      expression levels as well as significant inhibition in the activity of both the
      SLC23A1 and SLC23A2 promoters. Similarly, exposure of mice to ETEC led to a
      significant inhibition in intestinal AA uptake and reduction in mSVCT1 and mSVCT2
      protein, mRNA and heterogeneous nuclear RNA (hnRNA) expression levels. Inhibition
      was caused by the action of heat labile enterotoxin (LT), as infecting Caco-2
      cells with LT-deficient ETEC (DeltaLT) failed to impact on AA uptake. Since LT
      activates adenylate cyclase we also examined the effect of dibutyryl-cAMP in AA
      uptake by Caco-2 cells and observed a significant inhibition. Furthermore,
      treating the cells with celastrol, a specific NF-kappaB inhibitor, significantly
      blocked the inhibition of AA uptake caused by ETEC infection. Together, these
      data demonstrate that ETEC infection impairs intestinal AA uptake through a cAMP
      dependent NF-kappaB mediated pathway that regulates both SLC23A1 and SLC23A2
      transcription.

PMID- 30285483
TI  - Introduction.

PMID- 30285484
TI  - Leadership Development Program for Nurses at a Healthcare for the Homeless
      Program: A Educational Intervention.
AB  - PURPOSE: This quality improvement, educational intervention project aimed to
      develop nurse leaders at a large urban federally funded Health Care for the
      Homeless Program (HCH), using the Nursing Leadership Institute Competency Model.
      METHODS: A leadership seminar series which addressed six leadership topics for
      homeless health care nurses was developed, implemented, and evaluated using a one
      group pre/posttest design. The Leadership Practices Inventory (LPI) was also
      administered before and after the seminar series. RESULTS: There were
      statistically significant increases in new skills in the areas of interpersonal
      skills, personal mastery, systems thinking, and finance management. LPI scores
      improved after completion of the leadership seminar series. CONCLUSION:
      Participation in the leadership seminar series improved leadership skills and
      competencies of nurse leaders at the HCH. The acquired new knowledge may prepare
      homeless health nurses for sustained leadership roles which in turn will result
      in better meeting the needs of organizations providing care to homeless
      individuals.

PMID- 30285485
TI  - Using the Vulnerability Index(r) to Assess the Health Needs of a Homeless
      Community.
AB  - Compiling a health needs profile of a difficult-to-reach population such as the
      homeless can be challenging, particularly when using a community-based
      participatory research approach. In this article, we describe our experience
      using the Vulnerability Index(r) (VI), a questionnaire developed by 100,000 Homes
      Campaign to assess and prioritize individuals in need of housing based on their
      risk of mortality. We found the VI easy to administer and helpful in creating a
      health needs profile of participants.

PMID- 30285486
TI  - Enhancing Cultural Sensitivity in a Community Health Care Setting for LGBTQ
      Patients.
AB  - Lesbian, gay, bisexual, transgender, or queer (LGBTQ)-identified individuals,
      particularly transgender individuals, experience significant health inequities
      such as increased risk for chronic health conditions and mental health concerns.
      Discrimination by health care professionals is a major deterrent for LGBTQ
      individuals to seek health care. The purpose of the article is to offer practice
      recommendations using targeted community actions to enhance LGBTQ cultural
      sensitivity in community health care settings. Strategic planning, assessment for
      readiness to change, environmental strengths, weaknesses, opportunities, and
      threats analysis, and use of community resources are recommended as part of a
      basic model for change in a community setting. Outcomes are measured using a
      cultural competency tool.

PMID- 30285488
TI  - Engaging Nursing Students in a Rural Native American Community to Facilitate
      Cultural Consciousness.
AB  - Integrating cultural consciousness into nursing curricula is important for
      preparing a global nursing workforce. This article evaluated the impact of a
      teaching strategy designed to facilitate nursing students' cultural consciousness
      beyond the classroom during a 1-week field experience within a rurally isolated
      Native American community. Cultural consciousness health care is a central
      element of health care delivery that integrates clinical knowledge, sensitivity,
      and cultural understanding. This study used an intrinsic single case study design
      bounded by 30 nursing students' perceptions of their week-long immersion
      experience within a rurally isolated American Indian community. The reality of
      the situations they encountered did not match their expressed expectations nor
      their tacit assumptions. Evidence taken in situ from clinical reflections
      demonstrated most of the students wrestled with this mismatch, although they
      improved their clinical assessment, technical nursing, and intercultural
      communication skills. Evidence from end of course reflections demonstrated that
      two-thirds of the students integrated their preconceptions and their immersion
      experiences with cultural consciousness emerging in their reflections.

PMID- 30285489
TI  - The impact of morphophonological patterns on verb production: evidence from
      acquired morphological impairment.
AB  - Although much of the research on morphology and aphasia has focused specifically
      on the distinction between regular and irregular verb production, individuals
      with aphasia often present with differences in performance within these
      categories. While these within-category differences are relatively understudied,
      they have the potential to inform our understanding of the morphological
      processing system and treatment protocols for morphological impairment. The
      present study examines how morphophonological patterns in English impact past
      tense production within the categories of regular and irregular verbs based on
      errors of an individual with acquired morphological impairment. Acquired
      morphological impairment was demonstrated by performance on two reading tasks.
      First, the individual produced more final consonant deletion errors in
      morphologically complex words (prays->[pre]) compared to homophones (praise
      >[pre]). Second, morphological deletion errors were found to occur at comparable
      rates for inflected regular verbs (sinned->sin) and inflected irregular verbs
      (won->win), whereas the analogous error (e.g. ton->tin) never occurred on the
      monomorphemic pairs. In order to examine differences within each category, we
      used a past-tense elicitation task designed to analyse the effect of differences
      in morphophonological pattern frequency on accuracy and error patterns in
      production. We found production of both regular and irregular verbs was affected
      by the extent to which different morphophonological patterns are supported in the
      language (i.e. the number of phonologically similar words within the lexicon
      which take the same inflectional change). These results provide evidence that
      morphophonological patterns are encoded in a way that impact morphological
      production, a finding which has both clinical and theoretical implications.

PMID- 30285490
TI  - Epigenetics in Insects: Genome Regulation and the Generation of Phenotypic
      Diversity.
AB  - Epigenetic inheritance is fundamentally important to cellular differentiation and
      developmental plasticity. In this review, we provide an introduction to the field
      of molecular epigenetics in insects. Epigenetic information is passed across cell
      divisions through the methylation of DNA, the modification of histone proteins,
      and the activity of noncoding RNAs. Much of our knowledge of insect epigenetics
      has been gleaned from a few model species. However, more studies of epigenetic
      information in traditionally nonmodel taxa will help advance our understanding of
      the developmental and evolutionary significance of epigenetic inheritance in
      insects. To this end, we also provide a brief overview of techniques for
      profiling and perturbing individual facets of the epigenome. Doing so in diverse
      cellular, developmental, and taxonomic contexts will collectively help shed new
      light on how genome regulation results in the generation of diversity in insect
      form and function. Expected final online publication date for the Annual Review
      of Entomology Volume 64 is January 7, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30285491
TI  - Biology and Control of the Khapra Beetle, Trogoderma granarium, a Major
      Quarantine Threat to Global Food Security.
AB  - The khapra beetle, Trogoderma granarium, is a voracious feeder of stored products
      and is considered one of the most important quarantine pests globally. Its
      ability to survive for long periods under extreme conditions facilitates its
      spread through international commerce, which has led to invasions of new
      geographic regions. The khapra beetle is an important quarantine pest for many
      countries, including the major wheat-producing countries the United States,
      Canada, Russia, and Australia, and has been classified as one of the 100 worst
      invasive species worldwide. This species cannot always be controlled by
      insecticides and other nonchemical methods that are usually effective against
      other pests of stored products, particularly owing to its diapausing late larval
      stage. It can rapidly develop at elevated temperatures and under dry conditions,
      which are not favorable for many major stored-product insects. We synthesize key
      published work to draw attention to advances in biology, detection and control of
      the khapra beetle, and directions to consider for future research. Expected final
      online publication date for the Annual Review of Entomology Volume 64 is January
      7, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for
      revised estimates.

PMID- 30285492
TI  - Management of multiple myeloma bone disease: impact of treatment on renal
      function.
AB  - INTRODUCTION: Bone disease (BD) is one of the most common features of multiple
      myeloma. Seventy to eighty percent of patients at diagnosis present with lytic
      lesions which may lead to skeletal-related events. Areas covered: The aim of this
      review is to present the possible adverse profile of bisphosphonates (BPs) on
      renal function, the underlying mechanisms by which BPs may affect renal function
      and the novel therapeutic approaches on myeloma bone disease management. Expert
      commentary: BPs remain the cornerstone in the management of myeloma-related BD.
      Zoledronic acid and Pamidronate are currently the gold standard, however cannot
      be used in patients with severe renal dysfunction. Renal impairment is another
      hallmark of myeloma with approximately 60% of the patients presenting with or
      developing renal dysfunction during the disease course. Although BPs rarely cause
      renal impairment, they should be administered with caution in patients with
      impaired renal function. The exact mechanism by which BPs cause renal impairment
      is yet to be elucidated. Another promising agent is denosumab, a RANKL inhibitor,
      which can be administrated regardless of renal function and does not need the
      relevant dose-adjustments.

PMID- 30285493
TI  - Understanding Motivations and Player Experiences of Older Adults in Virtual
      Reality Training.
AB  - OBJECTIVE: We studied which games and underlying game mechanics are considered
      motivating by older adults, so that designers and therapists make informed
      choices when designing or selecting virtual reality (VR)-training interventions.
      MATERIALS AND METHODS: We conducted a repeated measures design with 30 older
      participants, who played eight different VR-training games and afterward filled
      out the intrinsic motivation inventory (IMI). Differences in intrinsic motivation
      between games were analyzed using Friedman's tests. In addition, in-depth
      interviews were conducted according to the laddering technique, to unveil the
      underlying game mechanics that lead to the players preferences. RESULTS: IMI
      scores were relatively high for all games, indicating that these VR games seem
      effective for inducing a high intrinsic motivation. Wii yoga and Kinect
      Adventures were the highest scoring games on all but the negative subscale
      tension. Both games provided regular positive feedback. An important game
      mechanic was Variation, which showed a strong link to important values such as:
      to Stay Focused, Improve Fitness, and Health and Independency. Furthermore, the
      game mechanics Visual Feedback and Positive Feedback, which lead to an increased
      Drive to Perform, were perceived valuable. Seemingly contradicting, but both
      important attributes such as Speed versus Slow Movements emphasize the importance
      of designing VR training that adapts to the skill level of the player.
      CONCLUSION: We have shown that games with different game mechanics can induce
      high intrinsic motivation. When designing or selecting VR balance training games
      for older adults, these game mechanics should be incorporated to optimize a
      positive user experience and increase intrinsic motivation.

PMID- 30285494
TI  - Associations between distress tolerance and asthma symptoms and quality of life.
AB  - OBJECTIVE: Given the robust associations between anxiety and asthma, the purpose
      of the current study was to explore associations between asthma outcomes and
      tolerance for negative affective states (i.e. distress tolerance) as well as
      tolerance for the specific negative emotional states of anxiety and fear.
      METHODS: Participants were 61 nonsmoking adults with asthma (61.9% female, 54.8%
      African-American, Mage = 34.72, SD = 13.58) who underwent spirometry and
      completed self-report measures. RESULTS: After controlling for the effects of
      age, race and the physical concerns domain of anxiety sensitivity, poorer global
      distress tolerance and tolerance for fear and anxiety each significantly
      predicted poorer lung function (8.7-13.8% variance), asthma control (4.9-8.8%
      variance) and asthma-related quality of life (6.7-8.9%). CONCLUSIONS: These
      findings suggest that targeting distress tolerance, specifically tolerance of
      fear and anxiety, may be helpful in improving asthma outcomes.

PMID- 30285495
TI  - The future of febuxostat after the Cardiovascular Safety of Febuxostat and
      Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) trial:
      who CARES?

PMID- 30285496
TI  - On the Road to Breeding 4.0: Unraveling the Good, the Bad, and the Boring of Crop
      Quantitative Genomics.
AB  - Understanding the quantitative genetics of crops has been and will continue to be
      central to maintaining and improving global food security. We outline four stages
      that plant breeding either has already achieved or will probably soon achieve.
      Top-of-the-line breeding programs are currently in Breeding 3.0, where
      inexpensive, genome-wide data coupled with powerful algorithms allow us to start
      breeding on predicted instead of measured phenotypes. We focus on three major
      questions that must be answered to move from current Breeding 3.0 practices to
      Breeding 4.0: ( a) How do we adapt crops to better fit agricultural environments?
      ( b) What is the nature of the diversity upon which breeding can act? ( c) How do
      we deal with deleterious variants? Answering these questions and then translating
      them to actual gains for farmers will be a significant part of achieving global
      food security in the twenty-first century.

PMID- 30285497
TI  - A qualitative study of parent perspectives on barriers, facilitators and
      expectations for school asthma care among urban, African-American children.
AB  - OBJECTIVES: Minority children experience the disproportionate burden of asthma
      and its consequences. Studies suggest ethnic groups may experience asthma
      differently with varied perceptions and expectations among parents of African
      American and Latino children. Because parents coordinate asthma care with the
      school, where children spend a significant amount of their day, this study's goal
      was to determine parents' perspectives on school asthma management. METHODS:
      Focus groups were conducted with parents of children with asthma at four urban
      schools whose student population is predominantly African-American. A semi
      structured guide was utilized focusing on barriers, facilitators and expectations
      for asthma care at school. Grounded theory principles were applied in this study.
      RESULTS: Twenty-two parents (91% females) representing 13 elementary and 10
      middle school children with asthma (61% boys) participated in four focus groups.
      Most children (87%) had persistent asthma. The identified barriers to effective
      school-based asthma care included limited awareness of children with asthma by
      teachers/staff, communication issues (e.g. school/parent, within school),
      inadequate education and lack of management plans or systems in place. In
      contrast, the identified facilitators included steps that fostered education,
      communication and awareness, as supported by management plans and parent
      initiative. Parents described their expectations for increased communication and
      education about asthma, better systems for identifying children with asthma, and
      a trained asthma point person for school-based asthma care. CONCLUSIONS: Parents
      of children with asthma identified important barriers, facilitators and
      expectations that must be considered to advance school asthma management.
      Improved school-based asthma care could lead to better health and academic
      outcomes.

PMID- 30285498
TI  - Health beliefs associated with poor disease self-management in smokers with
      asthma and/or COPD: a pilot study.
AB  - BACKGROUND: Compared to nonsmokers, smokers with chronic disease are less likely
      to adhere to self-management recommendations for the management of their chronic
      conditions. Although the literature notes poor adherence trends in smokers,
      actual influences of adherence in these patients require further study. This
      study examines the health beliefs that influence self-management behaviors in
      smokers with chronic lung disease. METHODS: This prospective, cross-sectional
      study surveyed patients (n = 83) seen in the pulmonary outpatient clinics of the
      University Medical Center of New Orleans between November 2015 and February 2016.
      Eligible patients included those between 40-64 years old diagnosed with asthma
      and/or chronic obstructive pulmonary disease (COPD). Primary measures included
      perceived beliefs related to the susceptibility to asthma and/or COPD becoming
      worse, perceived barriers to adherence, and perceived benefits to adherence.
      Patient characteristics under-study included smoking status, race, gender, and
      diagnosis. Descriptive and chi-square analyses were performed to characterize the
      sample. Student's t and and regression analyses were conducted to examine the
      relationships between perceptions, smoking status, race, gender, and diagnosis.
      RESULTS: Compared to nonsmokers, smokers perceived their asthma and/or COPD
      becoming worse (p = 0.0023). Smokers also perceived more barriers (p < 0.0001),
      and fewer benefits to adherence than nonsmokers (p = 0.0021). CONCLUSION: The
      health beliefs of smokers may influence their self-management behaviors. Results
      of this study can inform the development of services that target smokers in order
      to improve adherence to self-management behaviors and health outcomes.

PMID- 30285499
TI  - Filling the patient-provider knowledge gap: a patient advocate to address asthma
      care and self-management barriers.
AB  - INTRODUCTION: In an ongoing study, a new clinical role adapted from a patient
      navigator called the patient advocate (PA) met with patients before medical
      visits, attended appointments and afterwards reviewed provider instructions. This
      qualitative analysis examines the perspectives of PAs and providers regarding
      their experiences with patients to understand how a PA can help patients and
      providers achieve better asthma control. METHODS: PAs recorded journal entries
      about their experiences with patients. Provider focus groups and interviews were
      conducted by researchers and transcribed. Analysis was based on the Grounded
      Theory approach for qualitative research, using open and then focused coding. Two
      researchers independently coded these sources until intercoder agreement was
      achieved. RESULTS: Upon review of 31 journal entries on PA experiences with 24
      patients and transcripts from 2 provider focus groups and 12 provider interviews,
      5 themes emerged surrounding asthma care and self-management: medication
      adherence, follow-up, communication, social determinants of health and time.
      While patients shared with PAs specific socioeconomic barriers to medication
      adherence and follow-up, providers often did not know about these problems and
      cited barriers to communication. Time restrictions on medical visits further
      limited communication. CONCLUSIONS: Perspectives reported here illustrate a gap
      in knowledge and understanding between patients and providers. The PA's unique
      relationship with patients and presence inside and outside of medical visits
      allowed them to learn contextual patient information unknown to providers. PAs
      and providers cited numerous ways PAs can help to improve patient-provider mutual
      understanding.

PMID- 30285500
TI  - Tofacitinib for the treatment of ulcerative colitis.
AB  - INTRODUCTION: New generations of small molecules are being developed for the
      treatment of ulcerative colitis. Among them, tofatinib (a Janus kinase (JAK)
      inhibitor) has demonstrated efficacy for inducing and maintaining remission and
      achieving mucosal healing with a reasonable safety profile. Oral administration
      is attractive for patients and lack of immunogenicity represents an advantage
      over biologic drugs. Areas covered: This review discusses the molecular aspects
      of the JAK-STAT pathway; the mechanism of action of tofacitinib pertinent to
      ulcerative colitis and the evidence on the efficacy of tofacitinib for achieving
      clinically relevant outcomes, including clinical remission, mucosal healing, and
      normalization of quality of life, as well as safety aspects with special
      attention to adverse events related to the mode of action of the drug. Expert
      commentary: Tofacitinib will be the first drug on the class of JAK inhibitors to
      be available for treatment of ulcerative colitis. The efficacy of the drug, with
      a rapid onset of action even in cases of severe colitis, oral administration, and
      possibility to use the drug intermittently without generating immunogenicity,
      will bring about a redesign of current treatment paradigms for ulcerative
      colitis.

PMID- 30285501
TI  - The usefulness of listening social media for pharmacovigilance purposes: a
      systematic review.
AB  - INTRODUCTION: Social media mining could be a possible strategy to retrieve drug
      safety information. The mining of social media is a complex process under
      progressive evolution, falling into three broad categories: listening (safety
      data reporting), engaging (follow-up), and broadcasting (risk communication).
      This systematic review is aimed at evaluating the usefulness and quality of proto
      signals by social media listening. Areas covered: In this systematic search,
      performed according to MOOSE and PRISMA statements, we selected studies,
      published in MEDLINE, EMBASE, and Google Scholar until 31 December 2017, that
      listened at least one social media to identify proto-adverse drug events and
      proto-signals. Expert opinion: The selected 38 studies identified serious and
      unexpected proto-adverse drug events characterized by poorer information quality
      as compared with spontaneous reporting databases. This feature allows rarely the
      evaluation of causal relationships. Proto-signals identified by social media
      listening had the potential of anticipating pre-specified known signals in only
      six studies. Moreover, the personal perception of patients reported in social
      media could be used to implement effective risk communication strategies.
      However, signal detection in social media cannot be currently recommended for
      routine pharmacovigilance, due to logistic and technical issues.

PMID- 30285503
TI  - Acute Oral Ingestion of a Multi-ingredient Preworkout Supplement Increases
      Exercise Performance and Alters Postexercise Hormone Responses: A Randomized
      Crossover, Double-Blinded, Placebo-Controlled Trial.
AB  - Multi-ingredient preworkout supplements (MIPS) are marketed as a means to
      increase exercise performance. The purpose of this study was to determine the
      effect of a single serving of Bang Pre-Workout Master Blaster (BMB) on upper- and
      lower-body power output and local muscular endurance. Ten resistance-trained
      males participated in two exercise testing sessions consisting of the vertical
      jump (VJ), seated medicine ball throw (SMBT), and local muscular endurance tests
      for the bench press (BP) and leg extension (LE) exercises at 70% of one
      repetition maximum. Participants consumed placebo (PLA) or BMB 30 minutes prior
      to each exercise session. No difference between trials was observed for SMBT
      distance or BP repetitions. Vertical jump (p = .006) and LE repetitions (p =
      .014) were greater for the BMB trial compared with placebo. A significant
      interaction between trial and time was observed for insulin-like growth factor-1
      (IGF-1; p = .044). Serum IGF-1 was significantly increased at both 30 PS (p =
      .004) and 30PX (p = .038) compared with BL for the BMB trial only. In conclusion,
      acute ingestion of BMB increased lower-body power and endurance as measured by
      the VJ and LE repetition tests, respectively, without altering hemodynamics.
      Furthermore, serum IGF-1 increased in response to acute exercise with BMB
      supplementation, but not with PLA. No differences in human growth hormone (HGH)
      or serum cortisol responses were observed between trials.

PMID- 30285502
TI  - Relationship between intra-operative vein graft treatment with DuraGraft(r) or
      saline and clinical outcomes after coronary artery bypass grafting.
AB  - BACKGROUND: Saphenous vein grafts (SVGs) remain the most often used conduits for
      coronary bypass grafting (CABG). Progressive intimal hyperplasia contributes to
      vein-graft disease and vein-graft failure (VGF). We compared the impact of
      intraoperative preservation of SVGs in a storage solution (DuraGraft(r)) versus
      heparinized saline on VGF-related outcomes after CABG. METHODS: From 1996 to
      2004, 2436 patients underwent isolated CABG with >= 1 SVG. SVGs were
      consecutively treated with DuraGraft in 1036 patients (2001-2004) and heparinized
      saline in 1400 patients (1996-1999). Short- (< 30 days) and long-term (>= 1000
      days) outcomes were assessed using repeat revascularization (primary end point),
      and major adverse cardiac events (MACE) consisting of the composite of death,
      nonfatal myocardial infarction, or repeat revascularization. RESULTS: Mean follow
      up in the DuraGraft group was 8.5 +/- 4.2 years and 9.9 +/- 5.6 years in
      controls. Short-term event rates were low and generally did not differ between
      groups. DuraGraft was associated with a 45% lower occurrence of nonfatal
      myocardial infarction after 1000 days (hazard ratio 0.55, 95% CI 0.41-0.74; P <
      0.0001). There was 35% and 19% lower long-term risk for revascularization (HR
      0.65, 95% CI 0.44-0.97; P = 0.037) and MACE (HR 0.81, 95% CI 0.70-0.94; P =
      0.0051), respectively, after DuraGraft. Mortality was comparable between both
      groups at 1, 5, and 10 years. There was no statistically significant association
      between DuraGraft exposure and time to death starting at 30 or 1000 days (HR
      0.91, 95% CI 0.76-1.09; P = 0.29). CONCLUSION: In this study, intraoperative
      treatment of SVGs with DuraGraft was associated with a lower risk of long-term
      adverse events suggesting that efficient intraoperative SVG treatment may reduce
      VGF-related complications post-CABG. These data warrant randomized clinical
      trials to validate these findings.

PMID- 30285504
TI  - Renal resistive index significantly increased in hypertensive children and it is
      independently related to the pulse pressure and left ventricular mass index.
AB  - BACKGROUND: To the best our knowledge there is no data in the literature related
      to changes in renal resistive index (RRI) values in children who have
      hypertension (HT). In this study, we aimed to investigate the changes of RRI
      values and it is usability in children with HT. METHODS: A total of 75 children;
      48 with newly diagnosed HT and 27 healthy controls were included in the study.
      Routine history, physical examination, and laboratory examinations were
      performed. Left ventricular (LV) dimensions and systolic-diastolic functions,
      septum and posterior wall thickness (IVSd and PWd) and LV mass index (LVMI) were
      calculated by echocardiography. In addition to routine renal ultrasonography
      (US), renal pulsatility indexes (RPI), accelerated time and RRI were measured.
      Increased RRI was accepted as >0.70. RESULTS: Increased RRI was detected in 25
      (52%) of HT patients. Systolic and diastolic blood pressure (SBP and DBP), and
      pulse pressure (PP), low-density lipoprotein cholesterol and triglyceride levels,
      RRI, RPI, kidney length, IVSd, PWd, and LVMI were significantly higher in
      patients with HT (both p < 0.05). SBP and PP, PWd, LV ejection fraction, LV
      fractional shortening, and LVMI were positively correlated with the RRI. High
      density lipoprotein cholesterol was negatively correlated with the RRI. Of these
      measurements, RRI values were found to be independently associated with PP and
      LVMI (p < 0.05). CONCLUSIONS: In hypertensive children, RRI was significantly
      higher than healthy controls and it is also related with LVMI and PP.

PMID- 30285505
TI  - Double stacking cryolipolysis treatment of the abdominal fat with use of a novel
      contoured applicator.
AB  - BACKGROUND: Cryolipolysis is a noninvasive method for the selective reduction of
      subcutaneous fat. The abdomen and flank area are most commonly treated sites and
      now the treatment efficacy became the important issue. OBJECTIVES: To evaluate
      the effectiveness and safety of double stacking cryolipolysis treatment with the
      novel contoured applicator for abdominal fat reduction. MATERIALS AND METHODS: 12
      healthy Korean were treated using cryolipolysis contact device. The device was
      applied on participant's left lower abdomen. Performance was held for 35 minutes
      and immediately repeated the second performance. The right abdomen was left
      untreated. Participants were examined with high resolution ultrasound and the
      depth of subcutaneous fat layer was measured initially and 8 weeks after the
      sessions. Any adverse events were assessed during the entire study period.
      RESULTS: The subjective reduction of abdominal fat was noted in most
      participants. No serious adverse events was reported. Reduction of subcutaneous
      fat layer depth was confirmed in high resolution ultrasound after 8 weeks of
      treatment. CONCLUSION: The results of this study indicate that abdominal fat can
      be reduced effectively by the novel cryolipolysis applicator. With subjective
      satisfaction of participants our study shows that double stacking treatment
      appears safe and well tolerated with enhanced treatment outcomes.

PMID- 30285506
TI  - Comparative efficacy of short-pulsed intense pulsed light and pulsed dye laser to
      treat rosacea.
AB  - BACKGROUND: Laser and light-based therapies have often been used successfully to
      treat rosacea. Recently, short-pulsed intense pulsed light (IPL) that emitted
      pulse durations down to 0.5 ms was found to be effective for rosacea treatment.
      OBJECTIVE: This study evaluated the efficacy of short-pulsed IPL in the treatment
      of rosacea compared with pulsed dye laser (PDL) using same pulse duration and
      fluence. MATERIALS AND METHODS: Nine patients with rosacea were enrolled in a
      randomized, split-face trial. Each treatment consisted of four sessions at three
      week intervals and followed up until three weeks after the last treatment.
      Efficacy was assessed by erythema, melanin index, physician's subjective
      evaluation, and patient's satisfaction. RESULTS: The mean change in erythema
      index was -4.93 +/- 1.59 for the short-pulsed IPL group and -4.27 +/- 1.23 for
      the PDL group. The mean change in melanin index was -2.52 +/- 2.45 for the short
      pulsed IPL group and -1.95 +/- 1.41 for the PDL group. There was no significant
      difference in either melanin or erythema index between short-pulsed IPL and PDL
      treatments, and there were no noticeable adverse events. CONCLUSIONS: There was
      no significant difference between PDL and short-pulsed IPL treatment using the
      same energies and pulse. Both PDL and short-pulsed IPL were satisfactory and safe
      for rosacea treatment.

PMID- 30285507
TI  - Greater occipital and supraorbital nerve blockade for the preventive treatment of
      migraine: a single-blind, randomized, placebo-controlled study.
AB  - OBJECTIVE: Nerve injections have been used for the acute and preventive treatment
      of migraine in recent decades. Most of these injections focused on greater
      occipital nerve (GON) blockade. However, few studies were placebo controlled, and
      only a few of them investigated GON and supraorbital nerve (SON) blockade
      together. This study aimed to evaluate the efficacy of GON and SON blockade with
      local anesthetics for the preventive treatment of migraine without aura. METHODS:
      Eighty-seven patients diagnosed with migraine without aura were included in the
      study. Patients were divided randomly. One group was injected with 1% lidocaine,
      the other group was injected with 0.9% saline. GON and SON injections were done
      bilaterally. The injections were repeated weekly for 3 weeks. Patients were
      followed up for 2 months to assess clinical response. RESULTS: Seventy-one
      patients completed the study. After 2 months, the number of headache days
      decreased significantly from 12.8 +/- 10.9 to 5.3 +/- 7.4, and VAS decreased from
      8.3 +/- 1.0 to 5.5 +/- 1.9 in the blockade group. The number of headache days
      decreased from 12.4 +/- 10.3 to 7.5 +/- 7.2 and VAS decreased from 8.2 +/- 1.1 to
      7.4 +/- 1.3 in the placebo group. Response was seen in 65.1% of the patients in
      the blockade group (65.4% for episodic migraine, 64.7% for chronic migraine) and
      28.6% of the patients in the placebo group. The difference was significant.
      CONCLUSIONS: The results suggest that GON and SON blockade with lidocaine was
      more effective than the placebo in the prophylactic treatment of both episodic
      and chronic migraine.

PMID- 30285508
TI  - Hypertensive emergencies in diabetic patients from predominantly African American
      urban communities.
AB  - AIM: The aim of this study was to identify risk factors for hypertensive
      emergencies in diabetic patients presenting with severely elevated blood
      pressure. METHODS: Using electronic medical records, this study identified
      diabetic patients with hypertensive crisis who presented to the emergency
      department of Newark Beth Israel Medical Center, Newark, NJ from June 2013 to May
      2016. Diabetic patients with hypertensive emergencies were compared with non
      diabetic patients based on important demographic and clinical characteristics.
      RESULTS: Patients with diabetes accounted for 52.27% of all hypertensive
      emergencies during the study period. There were 264 diabetic patients with
      hypertensive emergencies and 519 diabetic patients with hypertensive urgencies.
      The majority of patients were African Americans (88.6%). The odds of hypertensive
      emergencies were strikingly higher in diabetic patients with hyperlipidemia (OR
      1.66, 95% CI 1.23-2.24), coronary artery disease (OR 2.95, 95% CI 2.15-4.05),
      congestive heart failure (OR 6.28, 95% CI 4.49-8.80), renal insufficiency (OR
      2.84, 95% CI 2.10-3.86) and low hemoglobin (OR 0.9, 95% CI 0.84-0.97). Acute or
      worsening heart failure was the most frequent acute target organ injury (49.6%)
      followed by non-ST elevation myocardial infarction (41.7%). Diabetic and non
      diabetic patients had similar rates of target organ injuries. CONCLUSION: The
      development of hypertensive emergencies in patients with diabetes was not because
      of diabetes per se but because of coexisting highly elevated blood pressure.
      Tight blood pressure control may decrease the risk of hypertensive emergencies in
      this patient population.

PMID- 30285509
TI  - Efficacy and safety of noninvasive focused ultrasound for treatment of
      subcutaneous adiposity in healthy women.
AB  - INTRODUCTION: In recent years, a new method focused ultrasound (FUS) has been
      used in the treatment of localized fat. The objectives of this work were to
      evaluate the efficacy and safety of the FUS in the treatment of abdominal
      subcutaneous fat. MATERIALS AND METHODS: Thirty-one healthy women were divided
      into two groups: G1 (N = 7), 6 sessions, 3 passes, once a week and G2 (N = 23),
      10 sessions, 2 passes, twice a week. Outcome measures were reduction of
      circumference and fat thickness. Safety monitoring included laboratory testing
      (serum lipids profile and liver function tests) and adverse events were also
      assessed. Patient satisfaction and tolerance questionnaires were also applied.
      One patient underwent abdominoplasty and received a single session of FUS 24 h
      before surgery and a skin sample was collected for histological analysis.
      RESULTS: The results showed improvement in body contouring and reduction of the
      thickness of the fat layer observed by ultrasonography in both groups: G1 (P <
      0.001) and G2 (P < 0.0001). The histology showed disrupted adipocytes and
      collapsed membranes 24 h after the FUS treatment. CONCLUSION: FUS represents an
      effective and safe treatment for reducing localized adipose tissue by
      adipocytolysis.

PMID- 30285510
TI  - Relationship between the NF-kappaB1-94ins/del ATTG locus polymorphism and risk of
      hypertension in the Chinese Han population.
AB  - OBJECTIVE: The onset of essential hypertension is the result of a combination of
      genetic factors and the environment. The nuclear factor (NF)-kappaB1-94ins/del
      ATTG locus polymorphism is associated with the occurrence of various diseases.
      The purpose of this study was to find out the relationship between the NF-kappaB1
      94ins/del ATTG locus polymorphism and the risk of hypertension in the Chinese Han
      population. METHODS: A total of 585 Chinese Han patients with essential
      hypertension and 585 Chinese Han healthy volunteers were recruited. Polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed
      to analyze the genotype of the NF-kappaB1-94ins/del ATTG locus in all the
      subjects. RESULTS: For the NF-kappaB1-94ins/del ATTG locus, the dominant
      (adjusted odds ratio [OR] = 1.31, 95% confidence interval [CI] = 1.13-1.54, P <
      0.001), recessive (adjusted OR = 1.17, 95% CI = 1.02-1.32, P = 0.03) and additive
      (adjusted OR = 1.19, 95% CI = 1.03-1.36, P = 0.01) models showed significant
      increase in the risk of hypertension. The NF-kappaB1-94ins/del ATTG locus II
      genotype was an independent risk factor for hypertension (OR = 1.15, 95% CI =
      0.78-1.69, P = 0.02). The interaction between the NF-kappaB1-94ins/del ATTG locus
      polymorphism and BMI, alcohol consumption, and diabetes significantly increased
      the risk of hypertension (OR = 1.71, 95% CI = 1.26-1.86, P < 0.01). CONCLUSION:
      The NF-kappaB1-94ins/del ATTG polymorphism is an independent risk factor for
      essential hypertension. The NF-kappaB1-94ins/del ATTG locus, obesity, drinking,
      and diabetes also interact to yield a higher risk of hypertension.

PMID- 30285511
TI  - A successful bronchial thermoplasty procedure in a "very severe" asthma patient
      with rare complications: a case report.
AB  - INTRODUCTION: Bronchial thermoplasty (BT) is a unique bronchoscopic treatment for
      severe asthma that utilizes radiofrequency ablation to reduce smooth muscle in
      the bronchial walls. Current studies mainly focused on uncontrolled severe asthma
      with a forced expiratory volume in 1 second (FEV1) above 60% and associated
      complications, no human studies have performed on "very severe" asthma as well as
      its complications. CASE STUDY: We present a 60-year-old male with more than 15
      years history of very severe asthma, who underwent BT. His FEV1 was only 20.4%
      predicted, which would have excluded him from all prior clinical trials of BT.
      The first BT procedure occurred without an issue. After the second BT procedure,
      he experienced severe dyspnea due to an infection with a non-flu respiratory
      virus. This illness was complicated by the formation of a pulmonary cyst. During
      recovering from the third procedure, he developed stomach stones. This is mainly
      related with taking large amounts of hawthorn previously, also cannot exclude the
      role of thermal energy injury on gastrointestinal nerve function. RESULTS:
      Despite these unexpected complications, his quality of life greatly improved
      after BT, yet his lung function did not improve. CONCLUSION: This case is the
      first to describe BT procedures in patient with this level of lung function
      compromise, although accompanied with rare complications; our report indicates BT
      may be an opportunity and choice for the "very severe" asthma patients.

PMID- 30285512
TI  - The Effect of a Polysaccharide-Based Multinutrient Dietary Supplementation
      Regimen on Infections and Immune Functioning in Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is a progressive neurodegenerative disease associated
      with increased infection rates, chronic inflammation, and premature death.
      Optimization of nutritional status via dietary supplementation may improve immune
      function in people suffering from MS and lead to decreased rates of infection.
      Fifteen individuals with a diagnosis of relapsing-remitting MS for an average of
      12.4 years (SD =7.4; R = 2, 25) were enrolled in a one-year open-label clinical
      trial. Participants consumed a broad-spectrum dietary supplement regimen
      containing polysaccharides, phytochemicals, antioxidants, vitamins, and minerals
      three times per day. The occurrence of infections and a panel of cytokines,
      growth factors, and T- and B-cell subsets were assessed at baseline and 12
      months. Seven female and 8 male participants with an average age of 51.3 years
      (SD =7.2; R = 38, 65) completed the study. At the end of the intervention,
      participants had fewer total infections (M = 7.9, SD =8.1 at baseline and M =
      2.5, SD =4.3 at 12-month follow-up). At 12 months, IL-2, TNF-alpha, EGF, and CD95
      + CD34+ significantly increased, while IL-1beta significantly decreased. No major
      adverse effects were reported; only mild gastrointestinal intolerance was
      reported in four cases. A decreased occurrence of infection was observed in MS
      patients treated with 12 months of a polysaccharide-based multinutrient dietary
      supplement. Significant changes were also noted in several key biomarkers that
      would be physiologically favorable to the MS population. Thus, the results of
      this study suggest an immunomodulatory effect of the dietary supplement regimen
      studied.

PMID- 30285513
TI  - Successful hyaluronic acid filler injection in a chronic myeloid leukemia patient
      taking imatinib mesylate.
AB  - Dermal fillers are highly favored around the globe as minimally invasive or
      nonsurgical procedures. Imatinib mesylate is the first-line treatment for
      patients diagnosed with chronic myeloid leukemia. However, some studies describe
      that imatinib mesylate may increase the tendency of skin fragility which can lead
      to easy bruising and hyperpigmentation after invasive skin procedures. Yet, to
      our knowledge, no studies have described any successful dermal filler injection
      performed on patients who are under imatinib mesylate treatment. Hence, we
      present a case successfully treated with hyaluronic acid filler injection on a
      patient under imatinib mesylate treatment. We carefully propose that hyaluronic
      acid filler can be an effective means of rejuvenation and cosmetic enhancement
      for those under imatinib mesylate treatment.

PMID- 30285514
TI  - Choroidal Vascularity Index and Choroidal Thickness in Human Leukocyte Antigen
      B27-Associated Uveitis.
AB  - PURPOSE: To assess choroidal thicknesses and choroidal vascularity index (CVI) in
      HLA-B27-associated uveitis. METHODS: Medical records of 45 treatment-naive
      unilateral HLA-B27-associated uveitis patients presenting with first episode and
      with onset time of < 1-week were reviewed. RESULTS: Mean choroidal thickness was
      275.98 +/- 71.62 in acute phase and 254.93 +/- 73.48 after resolution (p = .003).
      Mean CVI was 34.75 +/- 3.08 in acute phase and 33.56 +/- 2.48 after resolution (p
      < .001). Interestingly, even in fellow eyes, there were relative retinal and
      choroidal thickening and relative choroidal vascular engorgement in acute phase,
      but these differences were not significant. Degree of anterior chamber
      inflammation was correlated with relative choroidal vascular engorgement (p =
      .001) and choroidal thickening (p = .044). CONCLUSION: Eyes with acute HLA-B27
      associated uveitis exhibited choroidal thickening with increased choroidal
      vascularity that subsequently decreased after uveitis resolution. These were
      evident even in patients without posterior segment involvement.

PMID- 30285515
TI  - Peptidyl arginine deiminase inhibition suppresses arthritis via decreased protein
      citrullination in joints and serum with the downregulation of interlukin-6.
AB  - OBJECTIVE: To explore the relevance of citrullinated proteins and anti
      citrullinated protein antibodies (ACPA) via protein arginine deiminase (PAD)
      inhibition in peptide glucose-6-phosphate isomerase-induced arthritis (pGIA).
      METHODS: Cl-amidine, a PAD inhibitor, was injected into pGIA. Clinical scores and
      histopathological findings of ankle joints were assessed. Serum ACPA titers were
      analyzed using ELISA. Citrullinated protein expression in joints and sera were
      examined with immunohistochemistry and Western blot analysis, respectively. Serum
      levels of IL-6, TNFalpha, and IL-1beta were measured with cytometric bead array
      (CBA). Gene expression levels of IL-6 and TNFalpha in joints, lymph nodes, and
      spleens were analyzed with quantitative PCR. GPI-specific productions of IFNgamma
      and IL-17 from T cells in lymph nodes were evaluated. RESULTS: Cl-amidine
      treatment significantly reduced arthritis severity while ACPA titers tended to be
      lower, but not significantly different compared to the control. Citrullinated
      proteins in joints and sera from treated mice were clearly decreased. With Cl
      amidine treatment, serum IL-6 levels were significantly decreased, and IL-6 and
      TNFalpha gene expression were significantly reduced in joints. IL-17 production
      from GPI-specific T cells tended to be lower in Cl-amidine-treated mice, but not
      significantly different. CONCLUSION: Our results suggested that PAD-mediated
      citrullinated protein was involved in the pathogenesis of arthritis via IL-6.

PMID- 30285516
TI  - A benefit and the prospects of IL-6 inhibitors in idiopathic multicentric
      Castleman's disease.
AB  - Castleman's disease (CD), a heterogeneous group of lymphoproliferative disorders,
      is divided into unicentric CD (UCD) and multicentric CD (MCD) based on the number
      of regions of enlarged lymph nodes with characteristic histopathologic features.
      The clinical pictures and treatment differ greatly between these UCD and MCD. In
      MCD, cases of human herpesvirus 8-negative patients with unknown etiology are
      defined as idiopathic MCD (iMCD). Most cases of UCD are treatable by surgical
      excision. The prognosis of iMCD varies, and it may be challenging to achieve
      remission. Glucocorticoids are initiated as the first choice for therapy, but for
      glucocorticoid-resistant cases, interleukin (IL)-6 inhibition is initiated.
      However, an IL-6 inhibitor is not effective for all iMCD cases, and refractory
      cases occur despite these treatments. In this review, we briefly summarize the
      role of IL-6 in iMCD, and we discuss the efficacy that has been reported for
      tocilizumab (TCZ), the anti-IL-6 receptor antibody, for patients with iMCD in
      Japan. Factors predicting the therapeutic response to IL-6 remain to be
      identified, and the verification of the long-term safety of IL-6 inhibition is
      needed.

PMID- 30285517
TI  - Flow cytometry for pediatric platelets.
AB  - The ability of platelets to carry out their hemostatic function can be impaired
      in a wide range of inherited and acquired conditions: trauma, surgery,
      inflammation, pre-term birth, sepsis, hematological malignancies, solid tumors,
      chemotherapy, autoimmune disorders, and many others. Evaluation of this
      impairment is vitally important for research and clinical purposes. This problem
      is particularly pronounced in pediatric patients, where these conditions occur
      frequently, while blood volume and the choice of blood collection methods could
      be limited. Here we describe a simple flow cytometry-based screening method of
      comprehensive whole blood platelet function testing that was validated for a
      range of pediatric and adult samples (n = 31) in the hematology hospital setting
      including but not limited to: classic inherited platelet function disorders
      (Glanzmann's thrombasthenia; Bernard-Soulier, Wiscott-Aldrich, and Hermasky
      Pudlak syndromes, MYH9-dependent thrombocytopenia), healthy and pre-term
      newborns, acute and chronic immune thrombocytopenia, chronic lympholeukemia,
      effects of therapy on platelet function, etc. The method output includes levels
      of forward and side scatter, levels of major adhesion and aggregation
      glycoproteins Ib and IIb-IIIa, active integrins' level based on PAC-1 binding,
      major alpha-granule component P-selectin, dense granule function based on
      mepacrine uptake and release, and procoagulant activity quantified as a
      percentage of annexin V-positive platelets. This analysis is performed for both
      resting and dual-agonist-stimulated platelets. Preanalytical and analytical
      variables are provided and discussed. Parameter distribution within the healthy
      donor population for adults (n = 72) and children (n = 17) is analyzed.

PMID- 30285518
TI  - First-in-Human Phase I, Dose-Escalation and -Expansion Study of Telisotuzumab
      Vedotin, an Antibody-Drug Conjugate Targeting c-Met, in Patients With Advanced
      Solid Tumors.
AB  - PURPOSE: This first-in-human study evaluated telisotuzumab vedotin (Teliso-V),
      formerly called ABBV-399, an antibody-drug conjugate of the anti-c-Met monoclonal
      antibody ABT-700 and monomethyl auristatin E. MATERIALS AND METHODS: For dose
      escalation, three to six patients with advanced solid tumors were enrolled in
      eight cohorts (0.15 to 3.3 mg/kg). The dose-expansion phase enrolled patients
      with non-small-cell lung cancer (NSCLC) with c-Met-overexpressing tumors (c-Met
      positive; immunohistochemistry membrane H-score >= 150). Patients received Teliso
      V monotherapy intravenously on day 1 once every 3 weeks. Safety, tolerability,
      pharmacokinetics, and maximum tolerated dose were determined. RESULTS: Forty
      eight patients were enrolled (median age, 65 years; 35.4% NSCLC; median four
      prior therapies). One patient each in the 3.0-mg/kg (n = 9) and 3.3-mg/kg (n = 3)
      cohorts experienced dose-limiting toxicities. Although the maximum tolerated dose
      was not formally identified, the recommended phase II dose was defined as 2.7
      mg/kg on the basis of overall safety and tolerability. The most frequent
      treatment-emergent adverse events (any grade) were fatigue (42%), nausea (27%),
      constipation (27%), decreased appetite (23%), vomiting (21%), dyspnea (21%),
      diarrhea (19%), peripheral edema (19%), and neuropathy (17%). The most frequent
      Teliso-V-related grade >= 3 adverse events were fatigue, anemia, neutropenia, and
      hypoalbuminemia (4% each). Teliso-V and total antibody pharmacokinetics were
      approximately dose proportional, with a mean harmonic half-life of 2 to 4 days
      each. Prospective screening identified 35 (60%) of 58 patients with c-Met
      positive NSCLC. Of 16 patients with c-Met-positive NSCLC who were treated with
      Teliso-V 2.4 to 3.0 mg/kg, three (18.8%; 95% CI, 4.1% to 45.7%) achieved a
      partial response (median response duration, 4.8 months; median progression-free
      survival, 5.7 months; 95% CI, 1.2 months to 15.4 months). No other patients
      experienced a response. CONCLUSION: Teliso-V monotherapy demonstrated favorable
      safety and tolerability profiles, with encouraging evidence of antitumor activity
      in patients with c-Met-positive NSCLC.

PMID- 30285520
TI  - An Urban 9-1-1 System's Experience with Left Ventricular Assist Device Patients.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) are used with increasing
      frequency and left in place for longer periods of time. Prior publications have
      focused on the mechanics of troubleshooting the device itself. We aim to describe
      the epidemiology of LVAD patient presentations to emergency medical services
      (EMS), prehospital assessments and interventions, and hospital outcomes. METHODS:
      This is a retrospective chart review of known LVAD patients that belong to a
      single academic center's heart failure program who activated the 9-1-1 system and
      were transported by an urban EMS system to one of the center's 2 emergency
      departments between January 2012 and December 2015. Identifying demographics were
      used to query the electronic medical record of the responding city fire agency
      and contracted transporting ambulance service. Two reviewers abstracted
      prehospital chief complaint, vital signs, assessments, and interventions.
      Emergency department and hospital outcomes were retrieved separately. RESULTS:
      From January 2012 to December 2015, 15 LVAD patients were transported 16 times.
      The most common prehospital chief complaint was weakness (7/16), followed by
      chest pain (3/16). Of the 7 patients presenting with weakness, one was diagnosed
      with a stroke in the emergency department. Another patient was diagnosed with
      subarachnoid hemorrhage and expired during hospital admission. This was the only
      death in the cohort. The most common hospital diagnosis was GI bleed (3/16). The
      overall admission rate was 87.5% (14/16). CONCLUSIONS: EMS interactions with LVAD
      patients are infrequent but have high rates of admission and incidence of life
      threatening diagnoses. The most common prehospital presenting symptoms were
      weakness and chest pain, and most prehospital interactions did not require LVAD
      specific interventions. In addition to acquiring technical knowledge regarding
      LVADs, EMS providers should be aware of non-device-related complications
      including intracranial and GI bleeding and take this into account during their
      assessment.

PMID- 30285519
TI  - Real-Time Fatigue Mitigation with Air-Medical Personnel: The SleepTrackTXT2
      Randomized Trial.
AB  - OBJECTIVE: The aims of this study were: 1) to determine the short-term impact of
      the SleepTrackTXT2 intervention on air-medical clinician fatigue during work
      shifts and 2) determine the longer-term impact on sleep quality over 120 days.
      METHODS: We used a multi-site randomized controlled trial study design with a
      targeted enrollment of 100 (ClinicalTrials.gov NCT02783027). The intervention was
      behavioral (non-pharmacological) and participation was scheduled for 120 days.
      Participation was voluntary. All consented participants answered baseline as well
      as follow-up surveys. All participants answered text message queries, which
      assessed self-rated fatigue, sleepiness, concentration, recovery, and hours of
      sleep. Intervention participants received additional text messages with
      recommendations for behaviors that can mitigate fatigue. Intervention
      participants received weekly text messages that promoted sleep. Our analysis was
      guided by the intent-to-treat principle. For the long-term outcome of interest
      (sleep quality at 120 days), we used a two-sample t-test on the change in sleep
      quality to determine the intervention effect. RESULTS: Eighty-three individuals
      were randomized and 2,828 shifts documented (median shifts per participant =37,
      IQR 23-49). Seventy-one percent of individuals randomized (n = 59) participated
      up to the 120-day study period and 52% (n = 43) completed the follow-up survey.
      Of the 69,530 text messages distributed, participants responded to 61,571
      (88.6%). Mean sleep quality at 120 days did not differ from baseline for
      intervention (p > 0.05) or control group participants (p > 0.05), and did not
      differ between groups (p > 0.05). There was no change from baseline to 120 days
      in the proportion with poor sleep quality in either group. Intra-shift fatigue
      increased (worsened) over the course of 12-hour shifts for participants in both
      study arms. Fatigue at the end of 12-hour shifts was higher among control group
      participants than participants in the intervention group (p < 0.05). Pre-shift
      hours of sleep were often less than 7 hours and did not differ between the groups
      over time. CONCLUSIONS: The SleepTrackTXT2 behavioral intervention showed a
      positive short-term impact on self-rated fatigue during 12-hour shifts, but did
      not impact longer duration shifts or have a longer-term impact on sleep quality
      among air-medical EMS clinicians.

PMID- 30285521
TI  - An exploratory study on the role of vitamin D supplementation in improving pain
      and disease activity in rheumatoid arthritis.

PMID- 30285522
TI  - CFH Y402H polymorphism in Italian patients with age-related macular degeneration,
      retinitis pigmentosa, and Stargardt disease.
AB  - BACKGROUND: The complement system has been implicated in the pathogenesis of age
      related macular degeneration (AMD) and the CFH Y402H polymorphism has been
      suggested as a major risk factor for AMD. Recent evidences supported the role of
      inflammation in the pathogenesis of some retinal dystrophies. Aim of this study
      was to evaluate the prevalence of CFHY402H polymorphism in a group of Italian
      patients affected by atrophic AMD, Stargardt disease (STGD), or retinitis
      pigmentosa(RP). MATERIALS AND METHODS: Our case-control association study
      included 116 patients with atrophic AMD, 77 with RP, 86 with STGD, and 100
      healthy controls. All the patients were evaluated by a standard ophthalmologic
      examination and OCT. ERG was performed on STGD and RP patients. All the subjects
      underwent a blood drawing for genetic testing and the CFHY402H polymorphism was
      genotyped with the TaqMan real-time polymerase chain reaction single nucleotide
      polymorphism assay. RESULTS: The prevalence of the risk genotype C/C was higher
      in the AMD group than in controls (p < 0.001). The risk allele C was more
      frequent in the AMD group than in controls (p < 0.001). The prevalence of the
      risk genotype was higher in the RP patients than in controls (p < 0.001) and
      similarly the risk allele C was more frequent in the RP group (p = 0.008). The
      CFHY402H genotype distribution was not different between patients with STGD and
      the controls, for the biallelic (p = 0.531) and for the monoallelic (p = 0.318)
      evaluation. CONCLUSIONS: In our series of Italian patients, the CFHY402H genotype
      is associated with atrophic AMD and RP, but not with STGD. This result may
      support the hypothesis of a complement system dysregulation in the pathogenesis
      of AMD and RP.

PMID- 30285523
TI  - Proximal External Aortic Compression for Life-Threatening Abdominal-Pelvic and
      Junctional Hemorrhage: An Ultrasonographic Study in Adult Volunteers.
AB  - INTRODUCTION: Following life-threatening junctional trauma, the goal is to limit
      blood loss while expediting transfer to operative rescue. Unfortunately, life
      threatening abdominal-pelvic or junctional hemorrhage is often not amenable to
      direct compression and few temporizing strategies are available beyond hemostatic
      dressings, hypotensive resuscitation, and balanced transfusion. OBJECTIVES: In
      this study, we evaluated proximal external aortic compression to arrest blood
      flow in healthy adult men. METHODS: This was a simulation trial of proximal
      external aortic compression, for life-threatening abdominal-pelvic and junctional
      hemorrhage, in a convenience sample of healthy adult male volunteers. The primary
      end points were cessation of femoral blood flow as assessed by pulse wave Doppler
      ultrasound at the right femoral artery, caudal to the inguinal ligament.
      Secondary end points were discomfort and negative sequelae. RESULTS: Aortic blood
      flow was arrested in 12 volunteers. Median time to blood flow cessation was 12.5
      seconds. Median reported discomfort was 5 out of 10. No complications or negative
      sequelae were reported. CONCLUSION: This trial suggests that it may be reasonable
      to attempt temporization of major abdominal-pelvic and junctional hemorrhage
      using bimanual proximal external aortic compression. In the absence of immediate
      alternatives for this dangerous and vexing injury pattern, there appear to be few
      downsides to prehospital proximal external aortic compression while concomitantly
      expediting definite care.

PMID- 30285524
TI  - Characteristics and management of congenital anophthalmos and microphthalmos at a
      tertiary eye hospital.
AB  - PURPOSE: The purpose of the study is to evaluate demographic data and outcomes of
      the management of congenital anophthalmia/microphthalmia. METHODS: This
      retrospective, descriptive, cross-sectional study evaluated patients with
      congenital anophthalmia/microphthalmia managed from 2004 to 2014 at a tertiary
      hospital in Saudi Arabia. Data were collected on patient age, gender, cause,
      orbital status, laterality, systemic comorbidities, ocular evaluation, and
      management (type of surgery, type of orbital implant, and complications). The
      main outcome measure was the ability to hold the prosthesis. RESULTS: The study
      sample was composed of 513 eyes/sockets of 365 patients. Two-hundred and
      seventeen (59.4%) patients were unilateral cases. Forty-one (8%) sockets were due
      to congenital anophthalmia and 471 (92%) were due to microphthalmia. There were
      73.2% isolated cases and 28.5% with systemic involvement. Systemic involvement
      was more common in bilateral cases. The most commonly associated conditions were
      central nervous disorders. One-hundred and nineteen (46.7%) cases had parental
      consanguinity. Two hundred and eighteen eyes/sockets (163 patients) underwent
      surgery including conjunctival flap (38; 17.4%), evisceration (38; 17.4%),
      enucleation (16; 7.3%), or procedures to improve the anophthalmic socket volume
      (45; 20.6%). Volume enhancing procedures included polymethylmethacrylate orbital
      implants (26; 57.8%), expanders (11; 24.4%), integrated hydroxyapatite or
      polyethylene implants (2; 4.4%), and dermis-fat graft (6; 13.3%). In most cases,
      clinical or surgical management resulted in a successful outcome. CONCLUSION:
      Anophthalmia/Microphthalmia was detected in 36.5 patients/year. The majority had
      isolated microphthalmia. Good outcomes were achieved with clinical or surgical
      management in the majority of cases.

PMID- 30285526
TI  - Letter to editor: "is microtropia a reliable indicator for the presence of
      amblyopia in anisometropic patients?" by Lysons and Tapley.

PMID- 30285525
TI  - Focal and segmental glomerulosclerosis in murine models: a histological and
      ultrastructural characterization with immunohistochemistry correlation of
      glomerular CD44 and WT1 expression.
AB  - AIM: Focal segmental glomerulosclerosis (FSGS) is a common progressive chronic
      renal disease. Podocyte injury and loss are the postulated pivotal events that
      trigger FSGS. In this study, the authors aim to examine the evolution of FSGS in
      murine models histologically, ultrastructurally and immunohistochemically with
      special emphasis on podocytes and parietal epithelial cells (PECs). MATERIAL AND
      METHODS: FSGS resembling primary FSGS in humans was initiated in Wistar rats
      using intravenous Adriamycin injections. Blood and urine analysis were performed
      at 0, 8, and 12 weeks. Both the control kidneys and the test kidneys were
      harvested at 8 and 12 weeks, examined histologically and ultrastructurally and
      the findings correlated with the glomerular expression of immunostains specific
      for podocytes (WT-1) and for activated PECs (CD44). RESULTS: FSGS developed in
      both 8 and 12 weeks test groups showing progressive proteinuria, podocytopathy
      and segmental glomerular scarring. There was a decrease in the glomerular
      expression of WT-1 with a concurrent increase in the glomerular expression of
      CD44, indicating podocyte loss with synchronous increase in activated PECs. The
      evolving FSGS correlated negatively with podocytes and positively with activated
      PECs. CONCLUSION: Our study shows that with podocyte injury there is podocyte
      effacement and loss, proteinuria, glomerular segmental adhesion and scarring, all
      culminating in FSGS. In addition, there is activation, hyperplasia and
      hypertrophy of PECs. This demonstrates that both podocyte loss and PEC activation
      promote FSGS. Our findings are consistent with recent investigations. More
      studies are required to further understand the role of these cells in the
      evolution of FSGS and subsequently introduce new targeted treatment modalities.

PMID- 30285527
TI  - Early Menarche and Risk of Metabolic Syndrome: A Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: The association between age at menarche and metabolic syndrome was
      inconsistent across studies and remains unclear. We conducted a systematic review
      and meta-analysis of observational studies to assess the association between age
      at menarche and risk of metabolic syndrome, comprehensively. MATERIALS AND
      METHODS: The PubMed and ISI Web of Science databases were searched for all
      articles published through May 2017, and the reference lists of the retrieved
      articles were reviewed. Pooled relative risks (RRs) with 95% confidence intervals
      (CIs) were calculated using a random-effects model through combining the study
      specific estimates adjusting for potential confounders. RESULTS: Sixteen
      observational studies were eligible for the meta-analysis of age at menarche and
      metabolic syndrome, which included 13,657 cases among 51,453 subjects. The pooled
      RR of metabolic syndrome for the youngest versus the oldest categories of age at
      menarche was 1.62 (95% CI: 1.40-1.88) (p for heterogeneity = 0.01, I2 = 57.3%).
      The analysis of 1-year decrease in age at menarche conferred a pooled RR of 1.08
      (95% CI: 1.01-1.15), suggesting an 8% increase in risk of metabolic syndrome. The
      association between age at menarche and the risk of metabolic syndrome did not
      vary by study design, geographical region, number of subjects, and adjustment for
      confounders. CONCLUSIONS: Our findings from the current meta-analysis suggest
      that earlier menarcheal age is associated with higher risk of metabolic syndrome.
      Age at menarche may help identify women with higher risk of metabolic syndrome.
      Further well-designed cohort studies are warranted to provide definitive
      evidence.

PMID- 30285528
TI  - Registered blindness in Kuwait - 15 years of dynamic changes.
AB  - PURPOSE: Incidence rate of registered blindness and low vision (IR) among the
      Kuwaitis from 2005 to 2014 and longitudinal changes since 2000. METHODS: Data of
      newly certified Kuwaitis with best-corrected visual acuity 0.1 or less or visual
      field constriction to 20  degrees  or less in their better eye, aggregated in
      intervals from 2005 to 2009 and 2010 to 2014 and presented as IR per 100 000
      person years of observation by age, gender, severity and leading cause. RESULTS:
      Delayed certification resulted in rise of IR from 2005. IR of males declined
      since 2010, whereas among the females it continued rising at a slower rate. After
      2010 IR of patients from 40 to 59 years expanded significantly and declined in
      the group over 60 years. Retinitis pigmentosa was the leading cause driven by
      high prevalence of consanguineous marriages; the large difference between the
      males and females is due mainly to cultural factors. Diabetic complications
      escalated from 2005 affecting patients over 40 years. Glaucoma became the leading
      cause in the age over 60 years after 2005 and while the male patients decreased
      after 2010 by 18%, disabled females grew by further 35%. CONCLUSIONS:
      Demographic, social and behavioral factors had impact on the structure and time
      trends of registered blindness among the Kuwaitis. High prevalence of diabetes
      and aging of the population resulted in rise of certification from diabetic
      complications and glaucoma in the last 10 years.

PMID- 30285530
TI  - Management of Early Head and Neck Cancer in Elderly Patients.
AB  - Head and neck squamous cell carcinoma (HNSCC) frequently affects elderly
      patients. Given the frailty and comorbid conditions of this population as well as
      the potential toxicities associated with treatment, there is a risk of
      undertreatment in older patients. However, there is growing evidence that benefit
      with standard treatment is similar in the elderly and in younger patients. Few
      prospective trials specifically target the elderly, which forces clinicians to
      rely on subgroup analyses and retrospective data. Therefore, adequate
      pretreatment assessments are vital to anticipate factors that may contribute to
      morbidity during therapy. In addition, supportive care during treatment is
      essential. For patients of all ages who present with early or localized disease,
      curative treatment should be offered whenever possible. With more precise
      surgical and radiologic techniques, the ability to provide curative treatment
      while minimizing long-term toxicity has greatly improved. Not only our techniques
      but also our understanding of the disease have improved. Human papillomavirus
      (HPV)-related HNSCC has changed the treatment paradigm of advanced-stage disease
      because of the inherently better prognosis compared with tobacco- and alcohol
      related HNSCC. How this will affect early-stage disease remains to be seen, but
      de-escalated therapy may prove a suitable strategy in eligible elderly patients.
      With improved therapies and understanding of the disease, additional prospective
      trials must be carried out in the elderly population.

PMID- 30285529
TI  - What Can Be Done to Improve Research Biopsy Quality in Oncology Clinical Trials?
AB  - PURPOSE:: Research biopsy specimens collected in clinical trials often present
      requirements beyond those of tumor biopsy specimens collected for diagnostic
      purposes. Research biopsies underpin hypothesis-driven drug development,
      pharmacodynamic assessment of molecularly targeted anticancer agents, and,
      increasingly, genomic assessment for precision medicine; insufficient biopsy
      specimen quality or quantity therefore compromises the scientific value of a
      study and the resources devoted to it, as well as each patient's contribution to
      and potential benefit from a clinical trial. METHODS:: To improve research biopsy
      specimen quality, we consulted with other translational oncology teams and
      reviewed current best practices. RESULTS:: Among the recommendations were
      improving communication between oncologists and interventional radiologists,
      providing feedback on specimen sufficiency, increasing academic recognition and
      financial support for the time investment required by radiologists to collect and
      preserve research biopsy specimens, and improving real-time assessment of tissue
      quality. CONCLUSION:: Implementing these recommendations at the National Cancer
      Institute's Developmental Therapeutics Clinic has demonstrably improved the
      quality of biopsy specimens collected; more widespread dissemination of these
      recommendations beyond large clinical cancer centers is possible and will be of
      value to the community in improving clinical research and, ultimately, patient
      care.

PMID- 30285531
TI  - Rheumatic diseases associated with immune checkpoint inhibitors in cancer
      immunotherapy.
AB  - Immune checkpoint inhibitors (ICIs) have drastically altered cancer treatment
      paradigms, with increasing numbers of novel ICIs being currently evaluated in
      numerous clinical trials for various cancers. ICIs release "brakes" against tumor
      immunity to control cancer growth via T cell-dependent anti-tumor activity.
      Meanwhile, side effects associated with ICIs are directly related to their
      mechanism of action, as nonspecific immune activation targeting non-tumor organs
      results in undesirable off-target inflammation and autoimmunity. Accumulating
      data reveal that immune-related adverse events (irAEs) of ICIs in cancer patients
      can resemble various rheumatic diseases. Moreover, while patients with
      preexisting rheumatic diseases can theoretically experience irAEs and disease
      flares, observational studies have shown that ICIs can be used successfully in
      these patients. As ICIs continue to provide long-lasting disease control in
      cancer patients and their usage correspondingly increases, the rheumatologist
      will be managing new ICI-associated clinical entities mimicking common autoimmune
      diseases and will need to be prepared to rapidly diagnose and treat these irAEs.
      Early recognition and treatment of these rheumatic adverse events will allow for
      improved outcomes and quality of life for cancer patients faced with previously
      rapidly fatal disease.

PMID- 30285532
TI  - A high incidence of extensor pollicis brevis insertion into the distal phalanx in
      rheumatoid arthritis patients who required the surgical reconstruction for thumb
      boutonniere deformity.
AB  - OBJECTIVES: The aim of the current study was to investigate the pattern of
      extensor pollicis brevis (EPB) insertion macroscopically and histologically using
      cadaveric thumbs, and to compare the incidence of different insertions with that
      of thumb boutonniere deformity in rheumatoid arthritis (RA) patients who required
      surgical reconstruction. METHODS: We examined 103 thumbs of 58 adult cadavers
      with no evidence of RA, and reviewed the surgical records of 28 thumbs of 23 RA
      patients who underwent surgical reconstruction for thumb boutonniere deformity.
      The incidence of different insertion patterns of the cadaveric thumbs and the RA
      thumbs were compared using the Fisher's exact test. RESULTS: Macroscopic and
      histologic examination revealed that the insertion patterns of EPB could be
      divided into three groups: insertion into the base of the proximal phalanx (Type
      P1), integration of EPB into the dorsal fibrocartilage of the MCP joint (Type
      P2), and insertion into the distal phalanx (Type D). The incidence of Type D was
      significantly higher in RA patients with thumb boutonniere deformity (64%) than
      that in the non-RA cadavers (29%; P < 0.05). CONCLUSIONS: EPB is inserted into
      the distal phalanx more frequently in RA patients who require surgery for thumb
      boutonniere deformity than non-RA cadavers, suggesting an additional possible
      mechanism of this deformity.

PMID- 30285533
TI  - Safety and effectiveness of high-dose methotrexate (over 8 mg/week) in 2838
      Japanese patients with rheumatoid arthritis: A postmarketing surveillance report.
AB  - OBJECTIVES: To confirm the safety and effectiveness of high-dose (>8 mg/week)
      methotrexate (MTX) for the treatment of rheumatoid arthritis in Japan. METHODS: A
      postmarketing surveillance program enrolled Japanese patients with rheumatoid
      arthritis starting on high-dose MTX followed up for 24 or 52 weeks. Analyses for
      safety, risk factors affecting safety, and effectiveness were conducted. RESULTS:
      The safety/effectiveness analysis sets included 2838/2779 and 335/326 patients in
      the 24-week and 52-week follow-up groups, respectively. Incidence of adverse drug
      reactions (ADRs) and serious ADRs was 21.42% and 1.66% in the 24-week and 35.52%
      and 2.69% in the 52-week groups, respectively. The Disease Activity Score in 28
      Joints (DAS28) was significantly decreased as early as four weeks from the start
      of high-dose MTX; after 24-week (4.09-3.21) and 52-week treatment (3.91-2.80;
      both p<.001). In a majority of patients at baseline who had high-to-moderate
      disease activity, the remission rate (defined as DAS < 2.6) increased three-fold
      from 10.6% (baseline) to 33.0% (24-week) compared to patients with low disease
      activity whose remission rate increased two-fold from 24.0% (baseline) to 53.6%
      (24-week). CONCLUSION: High-dose MTX was well tolerated in Japanese patients,
      resulted in improved disease control, and can be considered a step forward in
      achieving treat-to-target goals.

PMID- 30285534
TI  - Should End-of-Life Preferences Be Discussed Routinely before High-Risk Surgery?
AB  - Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication
      of peritoneal dialysis. It is characterized by peritoneal neovascularization,
      fibrosis, and calcification ultimately leading to intestinal obstruction and
      eventual failure. Surgery for EPS has a mortality approaching 50% and most
      patients require some form of postoperative life-sustaining therapy (LST) during
      their admission. A 43-year-old gentleman with progressive EPS and significant
      comorbidities was assessed for enterolysis after a failed first attempt at
      another center. Because of his comorbidities, postoperative mortality was quoted
      above 50%. The patient favored surgery to improve his survival and quality of
      life, but was reluctant to receive prolonged LST in the event of failure of
      surgical therapy. The surgical team, in conjunction with a palliative care
      physician, therefore held extensive discussions with the patient and his partner
      regarding LST and its limitations. Clinical parameters to trigger a transition to
      palliative care were identified and agreed. Limitations on LST that are directly
      expressed by patients can represent a contraindication to surgery for many
      surgeons. Surgical Buy-In is a concept described as a perceived contract, or
      covenant, between the patient and clinician regarding implied consent for
      postoperative LST. Currently, preoperative discussions regarding limitations of
      LST are infrequent, and there can be reticence among patients and surgeons to
      have these conversations, leading to dissatisfaction on behalf of the patient and
      their family. After the Montgomery legal ruling, the provision and perception of
      informed consent are particularly pertinent. The palliative care physician is
      uniquely placed to contribute to such discussions as part of the surgical
      multidisciplinary team.

PMID- 30285535
TI  - Evaluation of pressurised carbon dioxide pre-treatment aimed at improving the
      sanitisation and anaerobic digestibility of co-settled sewage sludge.
AB  - This work reports on the use of pressurized CO2 pretreatment to improve methane
      yield and pathogen indicator organism die-off in co-settled sewage sludge (SS).
      Four semi-continuous mesophilic anaerobic digesters were fed on co-settled SS to
      establish a baseline for performance and stability. One pair of digesters was
      then fed with co-settled SS pretreated by P CO2 at 2800 kPa for 23 h. The trial
      continued for 70 days during which specific biogas and methane production,
      volatile solids destruction and loss of viability of Escherichia coli was
      monitored in test and control digesters. The pretreatment had no positive
      influence on any of these parameters, which was further confirmed using batch
      biochemical methane potential tests and direct measurement of die-off of E. coli
      and Salmonella enterica in samples of different sizes treated in pressure vessels
      of different sizes and in matrices of nutrient medium and co-settled SS.
      Pressurised CO2 pretreatment was effective at killing fecal indicator bacteria in
      nutrient medium but ineffectual in SS, strongly suggesting that the nature of
      suspending matrix was a principle determining factor. Paper concludes that
      pressurized CO2 pretreatment is not a satisfactory approach to improve either
      biogas production or pathogen destruction in anaerobic digestion.

PMID- 30285536
TI  - The Binary Bias: A Systematic Distortion in the Integration of Information.
AB  - One of the mind's most fundamental tasks is interpreting incoming data and
      weighing the value of new evidence. Across a wide variety of contexts, we show
      that when summarizing evidence, people exhibit a binary bias: a tendency to
      impose categorical distinctions on continuous data. Evidence is compressed into
      discrete bins, and the difference between categories forms the summary judgment.
      The binary bias distorts belief formation-such that when people aggregate
      conflicting scientific reports, they attend to valence and inaccurately weight
      the extremity of the evidence. The same effect occurs when people interpret
      popular forms of data visualization, and it cannot be explained by other
      statistical features of the stimuli. This effect is not confined to explicit
      statistical estimates; it also influences how people use data to make health,
      financial, and public-policy decisions. These studies ( N = 1,851) support a new
      framework for understanding information integration across a wide variety of
      contexts.

PMID- 30285537
TI  - The impact of Measles-Rubella vaccination on the morbidity and mortality from
      Congenital Rubella Syndrome in 92 countries.
AB  - Since 2011, GAVI, The Vaccine Alliance, has funded eligible countries to
      introduce rubella-containing vaccination (RCV) into their national schedule. Two
      key indicators used to monitor the impact - the future deaths and DALYs
      (Disability Adjusted Life Years) averted through vaccination conducted in
      specific periods - are poorly understood for rubella and Congenital Rubella
      Syndrome (CRS). We calculate these indicators using an age-structured dynamic
      transmission model for rubella, with historical vaccination coverage projections
      during 2001-30 in 92 low and middle-income countries considered most likely to
      require global support to achieve the Global Vaccine Action Plan's objectives.
      131,000 CRS deaths and 12.5 million DALYs may be prevented with immunization
      campaigns at best-estimate coverage during 2001-30, relative to those without
      additional support. The impact depended on the time period considered and the
      method for attributing deaths averted to vaccination in specific periods. The
      analyses support ongoing activities to reduce CRS-related morbidity and
      mortality.

PMID- 30285538
TI  - Effects of Quercetin on Lipid and Protein Damage in the Liver of Streptozotocin
      Induced Experimental Diabetic Rats.
AB  - Quercetin (QR) is part of a subclass of flavonoids called flavonols. We aimed to
      investigate the effect of QR on malondialdehyde (MDA), advanced oxidation protein
      products (AOPPs), and glutathione peroxidase (GSH-Px) activity in the liver of
      diabetic rats. We compared four groups of male adult Wistar albino rats: a
      control group, an untreated diabetic group, diabetic groups treated with QR, and
      QR group. Diabetes was induced by a single injection of streptozotocin (STZ) (50
      mg/kg). Animals were kept in standard condition. On the 31st day of the study,
      the liver tissue was removed for biochemical parameters and histopathological
      evaluations. In an untreated diabetic group, liver MDA and AOPP levels were
      significantly higher than all groups. QR treatment significantly decreased the
      increased MDA, AOPP levels, and increased the decreased GSH-Px enzyme activity in
      liver tissues. The QR-treated rats in the diabetic group showed an improved
      histological appearance. Lesser vesicular vacuolization and fibrotic areas were
      observed in the QR-treated diabetic group than in the diabetic group. The STZ
      induced liver injury is associated with oxidative stress, and coadministration of
      QR may reduce this damage effectively in a rat model. Our results are also
      supported by morphological improvement in liver tissue. Therefore, we think QR
      may be effective in treating hyperglycemia and oxidative damage in diabetes.

PMID- 30285540
TI  - Therapeutic Oligonucleotides: State of the Art.
AB  - Oligonucleotides (ONs) can interfere with biomolecules representing the entire
      extended central dogma. Antisense gapmer, steric block, spliceswitching ONs, and
      short interfering RNA drugs have been successfully developed. Moreover,
      antagomirs (antimicroRNAs), microRNA mimics, aptamers, DNAdecoys, DNAzymes,
      synthetic guide strands for CRISPR/Cas, and innate immunity-stimulating ONs are
      all in clinical trials. DNAtargeting, triplex-forming ONs and strand-invading ONs
      have made their mark on drug development research, but not yet as medicines. Both
      design and synthetic nucleic acid chemistry are crucial for achieving
      biologically active ONs. The dominating modifications are phosphorothioate
      linkages, base methylation, and numerous 2'-substitutions in the furanose ring,
      such as 2'-fluoro, O-methyl, or methoxyethyl. Locked nucleic acid and constrained
      ethyl, a related variant, are bridged forms where the 2'-oxygen connects to the
      4'-carbon in the sugar. Phosphorodiamidate morpholino oligomers, carrying a
      modified heterocyclic backbone ring, have also been commercialized. Delivery
      remains a major obstacle, but systemic administration and intrathecal infusion
      are used for treatment of the liver and brain, respectively. Expected final
      online publication date for the Annual Review of Pharmacology and Toxicology
      Volume 59 is January 6, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30285539
TI  - Ploidy Has Minimal Effect on Hypoxia Tolerance at High Temperature in Rainbow
      Trout (Oncorhynchus mykiss).
AB  - Polyploidy is an important driver of evolutionary change (generally via
      tetraploidy) and also serves a practical role in aquaculture and fisheries
      management (via triploidy). Fundamental changes in cell size and number that
      accompany polyploidy are predicted to affect cellular and whole-animal physiology
      due to constraints placed on surface-mediated processes at the cellular level,
      potentially altering environmental tolerances and optima. The aim of this study
      was to determine whether the documented reduction in thermal tolerance of aquatic
      polyploids is a result of their being less hypoxia tolerant. This was assessed by
      holding diploid and triploid rainbow trout for 1 h above their thermal optima in
      separate trials at eight temperatures between 20 degrees  and 27 degrees C and
      then rapidly reducing the oxygen tension (Po2) of the water and determining the
      nonlethal Po2 at which fish lost equilibrium. As expected, there was a highly
      significant ([Formula: see text]) effect of temperature on Po2 at loss of
      equilibrium. Although there was also a significant ([Formula: see text]) effect
      of ploidy on Po2 at loss of equilibrium, with triploid values higher than
      diploid, post hoc analyses showed no significant effect of ploidy at any specific
      temperature. Oxygen availability alone therefore does not appear to play a major
      role in determining the thermal tolerance of polyploids.

PMID- 30285541
TI  - Mind the Depth: Visual Perception of Shapes Is Better in Peripersonal Space.
AB  - Closer objects are invariably perceived as bigger than farther ones and are
      therefore easier to detect and discriminate. This is so deeply grounded in our
      daily experience that no question has been raised as to whether the advantage for
      near objects depends on other features (e.g., depth itself). In a series of five
      experiments ( N = 114), we exploited immersive virtual environments and visual
      illusions (i.e., Ponzo) to probe humans' perceptual abilities in depth and,
      specifically, in the space closely surrounding our body, termed peripersonal
      space. We reversed the natural distance scaling of size in favor of the farther
      object, which thus appeared bigger, to demonstrate a persistent shape
      discrimination advantage for close objects. Psychophysical modeling further
      suggested a sigmoidal trend for this benefit, mirroring that found for
      multisensory estimates of peripersonal space. We argue that depth is a
      fundamental, yet overlooked, dimension of human perception and that future
      studies in vision and perception should be depth aware.

PMID- 30285542
TI  - Amphiphilic block copolymer NPs obtained by coupling ricinoleic acid/sebacic
      acids and mPEG: Synthesis, characterization, and controlled release of
      paclitaxel.
AB  - Currently, nanoparticles (NPs) made of amphiphilic block copolymer are still an
      essential part of drug delivery system. Here, we report a novel amphiphilic block
      copolymer and paclitaxel (PTX)-loaded copolymer NPs for the controlled delivery
      of PTX. The block copolymer was synthesized via melt polycondensation method of
      methoxy poly(ethylene glycol) (mPEG), sebacic acid (SA) and ricinoleic acid (RA).
      A series of characterization approaches such as Fourier Transform Infrared
      Spectroscopy (FTIR), 1Hydrogen-Nuclear Magnetic Resonance (1H-NMR), Differential
      Scanning Calorimetry (DSC), X-Ray Diffraction (XRD) and Gel Permeation
      Chromatography (GPC) applied have shown that the amphiphilic block copolymer was
      prepared as designed. NPs prepared by nanoprecipitation method consist of mPEG
      segments as the hydrophilic shell and RA-SA segments as the hydrophobic core,
      hydrophobic PTX was encapsulated as model drug. Subsequently, Transmission
      Electron Microscopy (TEM) analysis indicated that the spherical NPs have
      effective mean diameters ranging from 100 to 400 nm. Dynamic Light Scattering
      (DLS) analysis also revealed the controllable NPs diameter by modulating the mass
      ratio of RA to SA and drug loading amount (DLA). Besides, biphasic profile with
      zero order drug release was observed in general in vitro release behaviors of PTX
      from NPs. Further investigation confirmed that the release behaviors depend on
      the crystallinity of hydrophobic RA-SA segments. Results above suggest that NPs
      with amphiphlic block copolymer mPEG-b-P(RA-SA)-b-mPEG have a remarkable
      potential as a carrier for hydrophobic drug delivery in cancer therapy.

PMID- 30285545
TI  - Antidiabetic Activity of Triticum aestivum Seed-Based Diet on Alloxan-Induced
      Diabetic Rats.
AB  - The antidiabetic activity of Triticum aestivum seed-based diet on alloxan-induced
      diabetic rats was investigated. Forty-eight male and female albino rats of four
      groups were used for this study. Rats were sacrificed on day 28 and organs of
      interest were excised. Triticum aestivum seed-based diet significantly (p < .05)
      reversed the levels of fasting blood glucose, albumin, globulin, bilirubin, urea,
      creatinine, Na+, and K+. In addition, diabetic rats fed Triticum aestivum seed
      based diet had significantly (p < .05) increased insulin and glycogen
      concentrations, activities of hexokinase, catalase, superoxide dismutase, and
      glutathione peroxidase and the levels of hematological parameters studied.
      Diabetic rats fed on Triticum aestivum seed had significantly (p < .05) reduced
      activities of glucose-6-phosphatase and fructose 1,6-diphosphatase and
      concentration of MDA and reversed activities of AST and GGT; ALP and regeneration
      of liver, kidney, and pancreas tissues compared favorably with the control group
      from histological examination results. Consumption of this diet may be useful for
      diabetes mellitus patients in ameliorating diabetes mellitus and its
      complications.

PMID- 30285546
TI  - Molecular self-assembly of copolymer from renewable phenols: new class of
      antimicrobial ointment base.
AB  - Ointments are highly viscous forms intended for external applications either
      medicated or non-medicated means. Formulation of ointment depends upon the base
      ingredients to measure the viscosity difference. Several limitations of ointment
      bases has been encountered timely as agglomeration, oil phase ingredients can
      form lumps, poor dispersion, poor drug delivery efficiency, make stained,
      immiscible, and difficult to wash off. Therefore, it is necessary to make a new
      type of ointment bases that can overcome those limitations. This review
      summarizes a new type of ointment base preparation from the copolymer of
      renewable phenolic derivatives. The nanohydrogel preparation from these
      copolymers are especially effortless and highly efficient in drug delivery,
      exhibited versatile biological activities such as antioxidant, anti-inflammatory
      and wound healing in addition to antimicrobial property. Molecular self-assembly
      mechanisms have been addressed for nanogel formulation. The strategy makes a
      significant value in health-care application and be supposed to come marketed
      soon.

PMID- 30285547
TI  - How age-of-death and mode-of-death impact perceptions of the deceased.
AB  - The goal of the current study was to explore how age-of-death (AOD) and mode-of
      death MOD simultaneously influence ratings of sympathy, empathy, and tragedy
      toward the deceased in order to assess social value. Three hundred and fifty
      eight participants, mainly undergraduates, responded to a series of vignettes
      that described a MOD (suicide, accident, or stroke) counterbalanced with three
      AODs (younger, middle-aged, and older). Overall, ratings of sympathy, empathy,
      and tragedy declined as AOD increased; however, the effect of AOD was not
      consistent across all MODs. The pattern of results suggests that death norms and
      perceived control of death impact the perception of the deceased.

PMID- 30285548
TI  - Link Between Facial Identity and Expression Abilities Suggestive of Origins of
      Face Impairments in Autism: Support for the Social-Motivation Hypothesis.
AB  - Individuals with autism spectrum disorder (ASD) often have difficulties with
      processing identity and expression in faces. This is at odds with influential
      models of face processing that propose separate neural pathways for the identity
      and expression domains. The social-motivation hypothesis of ASD posits a lack of
      visual experience with faces as the root cause of face impairments in autism. A
      direct prediction is that identity and expression abilities should be related in
      ASD, reflecting the common origin of face impairment in this population. We
      tested adults with and without ASD ( ns = 34) in identity and expression tasks.
      Our results showed that performance in the two domains was significantly
      correlated in the ASD group but not in the comparison group. These results
      suggest that the most likely origin for face impairments in ASD stems from the
      input stage impacting development of identity and expression domains alike,
      consistent with the social-motivation hypothesis.

PMID- 30285549
TI  - Kinetics and isotherm modeling of azoxystrobin and imidacloprid retention in
      biomixtures.
AB  - The paper reports the kinetics and adsorption isotherm modeling for imidacloprid
      (IMIDA) and azoxystrobin (AZOXY) in rice straw (RS)/corn cob (CC) and peat
      (P)/compost (C) based biomixtures. The pseudo-first-order (PFO), pseudo-second
      order (PSO), Elovich and intraparticle diffusion models were used to describe the
      kinetics. The adsorption data were subjected to the Langmuir and the Freundlich
      isotherms. Results (r2Adj values) suggested that the modified Elovich model was
      the best suited to explain the kinetics of IMIDA sorption while different models
      explained AZOXY sorption kinetics in different biomixtures (PFO in RS + C and RS
      + P; PSO in CC + P and Elovich in CC + C). Biomixtures varied in their capacity
      to adsorb both pesticides and the adsorption coefficient (Kd) values were 116.8
      369.24 (AZOXY) and 24.2-293.4 (IMIDA). The Freundlich isotherm better explained
      the sorption of both pesticides. Comparison analysis of linear and nonlinear
      method for estimating the Freundlich adsorption constants was made. In general,
      r2Adj values were higher for the nonlinear fit (AZOXY = 0.938-0.982; IMIDA = 0.91
      0.970) than the linear fit (AZOXY = 0.886-0.993; IMIDA = 0.870-0.974) suggesting
      that the nonlinear Freundlich equation better explained the sorption. The rice
      straw-based biomixtures performed better in adsorbing both the pesticides and can
      be used in bio-purification systems.

PMID- 30285550
TI  - Comparison of the Photodegradation of Imazethapyr in Aqueous Solution, on
      Epicuticular Waxes, and on Intact Corn (Zea Mays) and Soybean (Glycine Max)
      Leaves.
AB  - A direct, controlled comparison of the photodegradation of imazethapyr has been
      made between imazethapyr in aqueous solutions, imazethapyr on the surface of
      epicuticular waxes of corn and soybean plants, and imazethapyr on the surface of
      intact corn and soybean plant leaves. In some experiments, the imazethapyr
      solutions were allowed to evaporate partially or fully after application to
      better model environmental conditions. The photodegradation of imazethapyr was
      fastest in aqueous solutions (k = 0.16 +/- 0.02 h-1) and slowest on the surface
      of corn and soybean plants (kcorn = 0.00048 +/- 0.001 h-1 and ksoy = 0.00054 +/-
      0.003 h-1). Experiments allowing evaporation during irradiation have intermediate
      rate constants (e.g., kcorn = 0.082 +/- 0.005 h-1). Finally, identification of
      photoproducts was also examined on epicuticular waxes of corn and soybean plants
      for the first time.

PMID- 30285551
TI  - Comparison between personal sampling methodologies for evaluating diesel
      particulate matter exposures in mines: submicron total carbon corrected for the
      adsorption of vapor-phase organic carbon versus respirable total carbon.
AB  - In the mining industry, personal measurements of elemental and total carbon are
      frequently used as surrogates of diesel particulate matter (DPM) exposure, and
      the respirable or submicron fractions are usually measured. However, vapor-phase
      organic carbon (OC) can be adsorbed in the filters, interfering with total carbon
      results. This study presents a comparative evaluation between the submicron
      fraction of DPM concentrations corrected for the adsorption of the vapor-phase OC
      (dynamic blank), and the respirable fraction of DPM corrected for a field blank.
      Respirable and submicron fractions of total carbon (TCR and TC1) and elemental
      carbon (ECR and EC1) concentrations were sampled in parallel, in the workers'
      breathing zone, in an underground gold mine. A total of 20 full-shift personal
      samples were taken for each size fraction. Field blanks were collected each day
      for both the submicron and respirable fractions, while dynamic blank correction
      was also applied for the submicron fraction. TCR presented a larger and
      statistically different geometric mean concentration compared to TC1 (98 ug/m3
      versus 72 ug/m3; p = 0.01), while the concentrations of ECR and EC1 were not
      statistically different (58 ug/m3 versus 54 ug/m3; p = 0.74). Average TCR/ECR
      ratio was 1.7, while the TC1/EC1 ratio was 1.3. In addition, 93% of EC had an
      aerodynamic size lower than 1 um, while the proportion of TC particles in the
      submicron fraction was lower (73%). Finally, a similar quantity of OC was found
      when analysing the dynamic and field blanks of the filters with the submicron
      fraction selective size (24 ug and 22 ug, respectively). In conclusion, the
      correction for the vapor phase OC by the dynamic blank was not a significant
      correction in our study design compared to the field blank samples. This study
      suggests that the differences in TC may be explained by the different aerodynamic
      fractions of DPM collected. In addition, elemental carbon measurements did not
      seem to be extensively affected by the aerodynamic size of the particles
      collected.

PMID- 30285552
TI  - Development and validation of a quantitative method for thymidine phosphorylase
      activity in peripheral blood mononuclear cells.
AB  - The enzyme thymidine phosphorylase (TP) is important for activation of
      capecitabine and 5-fluorouracil. Assessment of TP phenotype might be suitable for
      identification of patients at risk of fluoropyrimidine-induced toxicity. In this
      paper, we describe the development and validation an assay for TP activity in
      peripheral blood mononuclear cells (PBMCs). The assay was based on ex vivo
      conversion of the TP substrate thymidine to thymine. The amount of thymine formed
      was determined by high-performance liquid chromatography - ultraviolet detection
      (HPLC-UV) with 5-bromouracil as internal standard. Lymphocytes and monocytes were
      purified from isolated PBMCs to examine cell-specific TP activity. TP activity in
      PBMCs demonstrated Michaelis-Menten kinetics. The lower limit of quantification
      was 2.3 ug PBMC protein and assay linearity was demonstrated up to 22.7 ug PBMC
      protein. Within-day and between-day precisions were <=9.2% and <=6.0%,
      respectively. Adequate stability TP activity was demonstrated after long-term
      storage of PBMC dry pellets and lysates at -80  degrees C. In monocytes, TP
      activity was approximately 3 times higher than in lymphocytes. Clinical
      applicability was demonstrated in samples that were collected from five cancer
      patients. A simple, precise and sensitive HPLC-UV assay for quantification of TP
      activity in PBMCs was developed that can be applied for clinical research.

PMID- 30285553
TI  - Parenting school-aged children after the death of a child: A qualitative study on
      victims' families of the Sewol ferry disaster in South Korea.
AB  - This study aims to identify parenting experiences after the death of a child.
      Using interpretive phenomenological analysis, we mapped the experiences of 16
      parents with school-aged surviving children after the death of their sibling to
      the 2014 Sewol ferry disaster in South Korea. Interviews illuminate five master
      themes of parenting surviving children following a child's death: (a) parental
      anxiety, (b) conflicts and obstacles in the parent-child relationship, (c)
      changes in parenting style, (d) striving to support children's grief, and (e)
      seeking outside help for parenting. Implications for supporting grieving parents
      and their children are discussed in light of the findings.

PMID- 30285554
TI  - The prevalence of elder abuse and neglect in Iran: a systematic review and meta
      analysis.
AB  - OBJECTIVE: The aim of this study was to estimate the prevalence of elder abuse
      and neglect in Iran. METHODS: We searched PubMed, Embase, Scopus, and PsycINFO by
      the end of 2017. The prevalence was calculated based on the percentage or the
      amount reported in the studies. Heterogeneity was assessed by the I2 statistic,
      and the data were combined using random effects model. The results were reported
      as the pooled estimates and the 95% confidence intervals (CIs). The review
      protocol was registered in PROSPERO (CRD42017070744). RESULTS: A total of 16
      studies involving 6,461 participants aged 60 years and over were included. The
      pooled prevalence for overall elder abuse was 45.7% (95% CI: 27.3-64.1, p <
      .001). DISCUSSION: The prevalence of elder abuse and neglect is substantial in
      the Iranian population aged 60 years and over. More research is needed to
      investigate the actual prevalence of elder abuse at the national level.

PMID- 30285555
TI  - Health-enhancing physical activity during practice among student football
      managers at a Division I university.
AB  - OBJECTIVE: Student football managers have demands on their time that may pose
      barriers to meeting recommended current physical activity (PA) guidelines. The
      study sought to assess the amount of PA obtained by student football managers at
      a NCAA Division I Football university. PARTICIPANTS: Subjects were student
      football managers (n = 14) with data collected in the fall 2015. METHODS:
      Participants wore an Omron HJ-720ITFFP pedometer for seven consecutive days
      during football activities only, while self-reporting their overall PA on day 7.
      Measures were analyzed using repeated measures and mixed-design ANOVAs. RESULTS:
      Managers averaged 8474 steps/day for each practice/game. All PA measures
      significantly varied by day and manager experience. Overall PA equated to 78
      hours of walking. CONCLUSIONS: Student football managers easily met and surpassed
      the recommended aerobic health-enhancing PA guideline. While their manager
      related PA was 140 minutes per week, other PA allowed them to easily reach
      significantly healthy levels of PA.

PMID- 30285556
TI  - Drunkorexia: A new term and diagnostic criteria.
AB  - Individuals who restrict their caloric intake and/or exercise excessively to
      mitigate the calories from alcohol consumption may suffer from an eating
      disorder, substance abuse disorder, or both. While the term "drunkorexia" has
      been used in both academic articles and popular culture, issues persist with
      respect to diagnosing and treating this condition. Classifying the behavior as a
      subcategory of Other Specified Feeding and Eating Disorders (OSFED) would provide
      patients with an increased likelihood of receiving insurance coverage for this
      condition. A consistent definition of this behavior and a more medically
      accurate/appropriate term-such as "alcoholimia"-are both needed to advance
      treatment and prevention efforts.

PMID- 30285557
TI  - Lived experience of a child's chronic illness and death: A qualitative systematic
      review of the parental bereavement trajectory.
AB  - To understand the lived experience of parents who have lost their child to a
      chronic life-limiting condition, six major databases were searched by adhering to
      the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines.
      Articles were screened for appropriateness using the Sample, Phenomenon of
      Interest, Design, Evaluation, Research type tool, and relevant qualitative
      studies were selected for full-text data analysis using Thematic Synthesis.
      Findings were categorized into 13 themes that were further organized into a four
      phase trajectory of parental bereavement experience of child loss, namely:
      Liminal Margin, Holding Space, Navigating Losses, and Reconstructing Lives. The
      findings are discussed in the light of existing literature with practical
      recommendations for enhancing parental bereavement support services.

PMID- 30285559
TI  - Questioning the Value of Fluorodeoxyglucose Positron Emission Tomography for
      Residual Lesions After Chemotherapy for Metastatic Seminoma: Results of an
      International Global Germ Cell Cancer Group Registry.
AB  - PURPOSE: Residual lesions after chemotherapy are frequent in metastatic seminoma.
      Watchful waiting is recommended for lesions < 3 cm as well as for
      fluorodeoxyglucose (FDG) positron emission tomography (PET)-negative lesions >= 3
      cm. Information on the optimal management of PET-positive residual lesions >= 3
      cm is lacking. PATIENTS AND METHODS: We retrospectively identified 90 patients
      with metastatic seminoma with PET-positive residual lesions after chemotherapy.
      Patients with elevated alpha-fetoprotein or nonseminomatous histology were
      excluded. We analyzed the post-PET management and its impact on relapse and
      survival and calculated the positive predictive value (PPV) for PET. RESULTS:
      Median follow-up time was 29 months (interquartile range [IQR], 10 to 62 months).
      Median diameter of the largest residual mass was 4.9 cm (range, 1.1 to 14 cm),
      with masses located in the retroperitoneum (77%), pelvis (16%), mediastinum
      (17%), and/or lung (3%). Median time from the last day of chemotherapy to PET was
      6.9 weeks (IQR, 4.4 to 9.9 weeks). Post-PET management included repeated imaging
      in 51 patients (57%), resection in 26 patients (29%), biopsy in nine patients
      (10%) and radiotherapy in four patients (4%). Histology of the resected specimen
      was necrosis in 21 patients (81%) and vital seminoma in five patients (19%). No
      biopsy revealed vital seminoma. Relapse or progression occurred in 15 patients
      (17%) after a median of 3.7 months (IQR, 2.5 to 4.9 months) and was found in 11
      (22%) of 51 patients on repeated imaging, in two (8%) of 26 patients after
      resection, and in two (22%) of nine patients after biopsy. All but one patient
      who experienced relapse were successfully treated with salvage therapy. The PPV
      for FDG-PET was 23%. CONCLUSION: FDG-PET has a low PPV for vital tumor in
      residual lesions after chemotherapy in patients with metastatic seminoma. This
      cautions against clinical decisions based on PET positivity alone.

PMID- 30285558
TI  - Cost-Effectiveness Analysis of Brentuximab Vedotin With Chemotherapy in Newly
      Diagnosed Stage III and IV Hodgkin Lymphoma.
AB  - PURPOSE: In a recent randomized, open-label trial (ECHELON-1), brentuximab
      vedotin (BV) combined with doxorubicin, vinblastine, and dacarbazine (AVD+BV)
      decreased the risk of progression in adults diagnosed with stage III or IV
      Hodgkin lymphoma (HL) compared with standard bleomycin-containing chemotherapy
      (doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD]). However, the cost
      effectiveness of incorporating BV (US$6,970 per 50-mg vial) into the first-line
      setting is unknown. PATIENTS AND METHODS: We constructed a Markov decision
      analytic model to measure the costs and clinical outcomes for AVD+BV compared
      with ABVD as first-line therapy in a cohort of patients with stage III or IV HL.
      Transition probabilities were estimated from ECHELON-1 by fitting parametric
      survival distributions. Lifetime direct health care costs, quality-adjusted life
      years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated
      for AVD+BV compared with ABVD from a US payer perspective. Our model was also
      used to estimate BV price reductions that would achieve more favorable cost
      effectiveness under indication-specific pricing. RESULTS: AVD+BV was associated
      with an improvement of 0.56 QALYs compared with treatment with standard ABVD.
      However, incorporating BV into first-line therapy led to significantly higher
      lifetime health care costs ($361,137 v $184,291), causing the ICER for AVD+BV to
      be $317,254 per QALY. If indication-specific pricing were implemented,
      acquisition costs for BV used in the first-line setting would need to be reduced
      by 56% to 73% for ICERs of $150,000 to $100,000 per QALY, respectively.
      CONCLUSION: Substituting BV for bleomycin during first-line therapy for stage III
      or IV HL is unlikely to be cost effective under current drug pricing. Should
      indication-specific pricing be implemented, significant price reductions for BV
      used in the first-line setting would be needed to reduce ICERs to more widely
      acceptable values.

PMID- 30285560
TI  - Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable
      Effect With Low Toxicity: Results From Two Nordic Lymphoma Group Trials With More
      Than 10 Years of Follow-Up.
AB  - PURPOSE: For indolent lymphoma, the optimal timing, sequence, and choice of
      therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group
      randomized trials, symptomatic or clearly progressing patients were treated first
      line with a rituximab-containing regimen without chemotherapy. The purpose of
      this study was to assess long-term survival, risk of transformation, and need of
      new therapies. METHODS: Data were collected at cross-sectional follow-up for 321
      patients with indolent lymphoma (84% with follicular lymphomas [FL]) included in
      one of two Nordic Lymphoma Group trials (accrual 1998 to 1999 and 2002 to 2008).
      All patients received first-line therapy with one or two cycles of four weekly
      infusions of rituximab 375 mg/m2, and 148 were randomly allocated to the addition
      of interferon alfa-2a. Follow-up data were retrieved from initial trial databases
      and medical records on repeated clinical evaluations. RESULTS: At the end of
      follow-up, 73% of patients were alive, with a median follow-up after random
      assignment of 10.6 years. Among all, 36% (38% with FL) had never needed
      chemotherapy. For patients with FL who required new therapy within 24 months
      because of early disease progression, the 10-year survival rate was 59% versus
      81% for those with longer remission. Interferon was not shown to improve long
      term outcome. Transformation was diagnosed in 20% of all patients (2.4% per
      person-year) and in 18% with FL. An additional malignancy was found in 12%.
      CONCLUSION: Approximately one third of patients with symptomatic indolent
      lymphoma (30% with FL, 23% without FL) did not need new therapy in the long term
      after first-line rituximab without chemotherapy. In the entire cohort, 10-year
      survival was excellent with no major safety issues, which suggests that
      chemotherapy can be delayed safely in the majority of patients.

PMID- 30285561
TI  - Reliance agreements and single IRB review of multisite research: Concerns of IRB
      members and staff.
AB  - The new National Institutes of Health (NIH) Policy on the Use of a Single
      Institutional Review Board (sIRB) for Multi-Site Research was adopted primarily
      to simplify and speed the review of complex multisite clinical trials. However,
      speeding review requires overcoming a number of obstacles. Perhaps the most
      substantial obstacle is the time and effort needed to develop reliance agreements
      among the participating sites. We conducted 102 semistructured interviews with
      sIRB personnel, including directors, chairs, reviewers, and staff, from 20 IRBs
      that acted as sIRBs for multisite research, including 6 commercial/independent
      sIRBs, and 10 university-based academic and 4 federal sIRBs. Almost without
      exception, the interviewees agreed that reliance agreements were complex,
      difficult to develop, and time-consuming. A major problem for relying sites was
      that different agreements specified different responsibilities for the relying
      sites. Attitudes differed about whether these problems will be resolved as IRB
      staff and managers become more experienced with sIRBs. However it is clear that
      the process of developing reliance agreements must be simplified. Federal
      assistance in standardizing at least some sections of reliance agreements might
      reduce the difficulties involved.

PMID- 30285562
TI  - Understanding factors related to nonsmoking intention among college students.
AB  - OBJECTIVE: While cigarette smoking in the United States has declined, the age
      range of smoking initiation has risen to include young adults. This study
      investigated the relationship of Theory of Planned Behavior constructs (TPB;
      attitudes, subjective norms, and perceived behavioral control [PBC]) to
      nonsmoking intention among college students. PARTICIPANTS: Participants were 619
      students at a Southeastern US university (69.8% female, 70.8% <= age 21, and
      73.5% white). METHODS: Students were recruited by email in March 2013 to
      participate in an online TPB-based questionnaire. RESULTS: Future-oriented
      attitudes and PBC predicted higher nonsmoking intention; subjective norms did
      not. Moderator analyses indicated injunctive norms were more influential for
      occasional smokers and PBC was less influential. CONCLUSIONS: Findings suggest
      TPB is useful in predicting nonsmoking intention, but differentially for
      nonsmokers and occasional smokers. Future work should consider the health-related
      utility of future-oriented attitudes toward nonhealth domains and the differing
      beliefs of occasional smokers.

PMID- 30285563
TI  - Understanding stress as an impediment to academic performance.
AB  - OBJECTIVES: Stress is the most commonly reported impediment to academic
      performance among college students. The objectives of this study were to examine
      the accuracy of these perceptions, identify demographic and psychosocial factors
      that distinguished among students who differed in perceptions of how stress
      affected their performance, and assess the relations between these factors and
      grade point average (GPA). PARTICIPANTS: Undergraduate students (N = 8,997) from
      20 Midwestern schools. METHODS: Participants completed online surveys during
      February-March 2015 that assessed perceived impediments to academic performance,
      cumulative GPA, demographic information, and psychosocial factors. RESULTS:
      Students who reported that stress affected their performance had lower GPAs, and
      reported more stress and lower coping self-efficacy, resilience, and social
      support. Male, heterosexual, and ethnic-minority students were less likely to
      report having stress (but did not have higher GPAs). CONCLUSION: Stress reduction
      interventions should target psychosocial factors related to perceiving stress as
      an impediment and to poorer performance.

PMID- 30285564
TI  - Actual and simulated weather data to evaluate wet bulb globe temperature and heat
      index as alerts for occupational heat-related illness.
AB  - Heat stress occupational exposure limits (OELs) were developed in the 1970s to
      prevent heat-related illnesses (HRIs). The OELs define the maximum safe wet bulb
      globe temperature (WBGT) for a given physical activity level. This study's
      objectives were to compute the sensitivity of heat stress OELs and determine if
      Heat Index could be a surrogate for WBGT. We performed a retrospective analysis
      of 234 outdoor work-related HRIs reported to the Occupational Safety and Health
      Administration in 2016. Archived NOAA weather data were used to compute each
      day's maximum WBGT and Heat Index. We defined the OELs' sensitivity as the
      percentage of incidents with WBGT > OEL. Sensitivity of the OELs was between 88%
      and 97%, depending upon our assumption about acclimatization status. In fatal
      cases, the OELs' sensitivity was somewhat higher (92% to 100%). We also computed
      the sensitivity of each possible Heat Index discrimination threshold. A Heat
      Index threshold of 80 degrees F (26.7 degrees C) was exceeded in 100% of
      fatalities and 99% of non-fatal HRIs. In a separate analysis, we created
      simulated weather data to assess associations of WBGT with Heat Index over a
      range of realistic outdoor heat conditions. These simulations demonstrated that
      for a given Heat Index, when radiant heat was included, WBGT was often higher
      than previously reported. The imperfect correlation between WBGT and Heat Index
      precluded a direct translation of OELs from WBGT into Heat Index. We conclude
      that WBGT-based heat stress exposure limits are highly sensitive and should be
      used for workplace heat hazard assessment. When WBGT is unavailable, a Heat Index
      alert threshold of approximately 80 degrees F (26.7 degrees C) could identify
      potentially hazardous workplace environmental heat.

PMID- 30285565
TI  - Women's knowledge about risk factors of breast cancer in a Brazilian community.
AB  - Knowledge about risk factors for breast cancer was identified as an important
      variable that affects women's avoidance behavior and their screening performance.
      The present study assessed women's knowledge about risk factors and associated
      socio-economic variables. Data from 417 women aged 20-86 years were obtained in
      Caico, Rio Grande do Norte, Brazil. In agreement with the recognition of 26
      potential risk factors and prevention behaviors, two groups with good (N = 203)
      and poor (N = 214) knowledge were formed, respectively. Having a close relative
      with cancer remained the unique significant variable in the adjusted model. Women
      without any close relative with cancer, were 1.54 (95% confidence interval [CI]
      1.036-2.288) times as likely to have poor knowledge, compared to women who had a
      close relative with cancer (p = 0.033). Other socio-economic variables, including
      income, employment status and educational level had no significant association
      with knowledge (p = 0.450, p = 0.914, p = 0.639, respectively). Of 417 women, 302
      (72.42%), 339 (81.29%), and 309 (74.10%), respectively, did not identify
      "physical inactivity," "overweight after menopause," and "no breastfeeding of
      children" as risk factors. Knowledge could help to avoid risk factors and
      motivate prevention behavior. Information about risk factors should be
      disseminated in health campaigns.

PMID- 30285566
TI  - Examining the transitions between living and dying roles at end-of-life.
AB  - Improvements in the diagnosis and disclosure of dying mean that nowadays dying
      people typically live with an awareness of their status for longer than they have
      previously. However, little is known regarding how transitions between living and
      dying roles occur during this time. In this grounded theory study, we
      investigated role transitions at end-of-life. We found that dying people
      periodically foreground and background living and dying selfhoods, focus on
      living day-by-day and goal-by-goal and reframe dying roles with an orientation to
      living. We argue that with better understanding of role transitions at end-of
      life more compassionate and responsive care becomes possible.

PMID- 30285567
TI  - Mind and mourning: The primacy of "we" in complicated grief.
AB  - Standard models of complicated grief rely on a self-other divided mind that
      reflects the physical separateness of individuals. In these models, grief
      persists for those mourners who cannot reorganize self-and-other mental
      representations or adapt to identity changes after loss. However, advances in
      cognitive science indicate that relationships are often processed via distributed
      social-cognitive coding whereby individuals together form a psychologically
      extended common mind. I propose a novel "we" hypothesis in which shared
      representations, rather than self-other distinctions, shape the mind for a
      subgroup of mourners with complicated grief. Recognition of "we-experiences" in
      mourning can enhance grief theory, research, and practice.

PMID- 30285568
TI  - National college health assessment sampling: Organizational barriers preventing
      black participation and organizational solutions for appropriate representation.
AB  - OBJECTIVE: This investigation longitudinally examined the participation of Black
      college students in the American College Health Association?s National College
      Health Assessment (ACHA-NCHA). PARTICIPANTS: All respondents to ACHA-NCHA from
      the years 2008, 2011, & 2014 were included in the analysis. METHODS: This study
      compared the descriptive demographic student characteristics from the 2008, 2011,
      & 2014 ACHA-NCHA data to the National Center for Education Statistics (NCES)
      college enrollment for the corresponding years. RESULTS: Despite constituting
      14.5% of the total enrollment in 4-year universities and colleges from 2005 to
      2013, Black students represented about 7% of the ACHA-NCHA respondents.
      CONCLUSION: Having a sample lacking valid representation of minorities can
      further lead to biased and flawed assumptions. Therefore, organizations such as
      ACHA should make concerted efforts to gather data that is reflective of national
      enrollment rates.

PMID- 30285569
TI  - Physical Activity, Health-Related Fitness, and Classroom Behavior in Children: A
      Discriminant Function Analysis.
AB  - PURPOSE: The purpose of this study was to examine the predictive relationship
      among physical activity, health-related fitness, and on-task classroom behavior
      in children using a discriminant function analysis. METHOD: Participants were a
      convenience sample of children (N = 533; Mage = 8.8 +/- 1.9 years) recruited from
      77 1st- through 5th-grade classrooms at 3 low-income schools in a capital city in
      the Southwest United States. Percent of the school day spent in sedentary
      behavior (%SED), moderate-to-vigorous physical activity (%MVPA), and health
      related fitness scores (body mass index [BMI] and Progressive Aerobic
      Cardiovascular Endurance Run [PACER] laps) were assessed during school hours.
      Classrooms were observed for on-task behavior during the academic year with the
      use of 5-s momentary time sampling methodology. A discriminant function analysis
      was performed using a binary on-task behavior outcome, stratified by an 80% on
      task behavior cut point. RESULTS: The results yielded 1 function (r2 = .26, F =
      13.1) explaining approximately one quarter of the total variance. The
      standardized function coefficients were -.29, .29, -.48, and .48 for %SED, %MVPA,
      BMI, and PACER laps, respectively. The sensitivity and specificity of the derived
      function for classifying a child into an on-task or off-task classroom were .79
      and .73, respectively. Children who belonged to classrooms that achieved 80% on
      task behavior displayed shorter times in sedentary behaviors (d = 1.01), lower
      BMI (d = 0.13), and higher PACER scores (d = 0.22) compared with children who
      belonged to off-task classrooms. CONCLUSION: School-day physical activity
      behaviors and health-related fitness scores can moderately discriminate children
      who belong to classrooms from low-income schools that are categorized as being
      sufficiently on task.

PMID- 30285570
TI  - Authenticity at Work: A Matter of Fit?
AB  - Authenticity at work refers to the extent to which a worker feels in touch with
      their true self while at work. At first sight this concept seems to overlap with
      the concept of person-environment (P-E) fit, that is, the degree to which an
      individual experiences good fit with their work environment. Drawing on a sample
      of 867 Dutch gifted workers, structural equation modeling was used to investigate
      (i) whether authenticity at work and P-E fit can be distinguished, and (ii) how
      authenticity at work and P-E fit were associated with employee well-being. As
      expected, confirmatory factor analysis revealed that authenticity at work and P-E
      fit were distinct from each other. Moreover, the mediated effect of authenticity
      at work was stronger for two negative forms of well-being (burnout and boredom)
      than for two positive forms of well-being (work engagement and job satisfaction).
      The theoretical and practical implications of these findings are discussed,
      especially focusing on the distinction between authenticity and P-E fit.

PMID- 30285571
TI  - Predictors of Therapeutic Outcome to Nucleotide Reverse Transcriptase Inhibitor
      in Hepatitis B Patients.
AB  - Hepatitis B is a clinically important public health issue. Infection leads to
      hepatocellular carcinoma. Therefore, patients need antiviral therapy for
      prolonged period to prevent the complication of the disease. Data concerning
      chronic hepatitis B (CHB) patients with high hepatitis B virus (HBV) DNA are
      limited. The aim of the study was to check the efficacy of the nucleoside reverse
      transcriptase inhibitors (tenofovir) in terms of suppression of HBV DNA. The
      secondary end point in the study is to evaluate trends of predictive variables
      that predict outcome of treatment. In this specific study, we evaluated 140 CHB
      male and female patients, of these 110 completed 48 weeks of treatment. On the
      basis of hepatitis B e antigen (HBeAg), patients were stratified; HBV DNA and
      hepatitis B surface antigen (HBsAg) levels were measured along with liver
      function tests. All enrolled patients were given tenofovir disoproxil fumarate
      300 mg daily before breakfast. Overall, 69.1% of patients showed virologic
      response. HBeAg-negative patient group showed 68% viral suppression and HBeAg
      positive patient group showed 45.9% over 24 months of treatment, while at 48
      months it was shown to be 76.7% and 54.1%, respectively. None of the patients
      suffered HBsAg loss during the 48 months. Baseline high HBV DNA level was found
      as a significant predictor of response (OR, 1.9; 95% CI = 1.23-3.9, p = 0.005).
      None of the patients observed had serious adverse events. Mutations in the RT
      region of polymerase gene are shown to be associated with resistance to antiviral
      drugs. Among patients suffering with chronic HBV infection, HBeAg-negative
      patient group have better virologic response as compared with HBeAg-positive
      group. Higher concentration of HBV DNA at baseline has negative prediction for
      sustained viral suppression. The A-B motif interdomain rtL122F mutation was found
      in nonresponder patients in our study. Another mutation rtN248H observed in E
      motif considered to have effect on DNA primer grip, which forms part of binding
      pocket.

PMID- 30285572
TI  - Own-Age Bias and Positivity Effects in Facial Recognition.
AB  - Background/Study Context - In the current study, we evaluated two age-related
      differences in recognition memory: the own-age bias, wherein older and younger
      adults best recognize those of their own age group, and an age-related positivity
      effect, wherein older adults recall positive emotional information better than
      negative information relative to younger adults. We sought to extend previous
      research that jointly investigated these variables in recognition memory. Methods
      - Younger (age 18 - 27) and older (age 62 - 80) adults completed an incidental
      encoding task on a sequence of 50 positive, negative, or neutrally valenced
      images of older and younger adult faces. After a distractor task, participants
      made forced-choice recognition judgments and rated their decision confidence for
      images that were repeated with the same or a different emotional expression, and
      for novel, previously unseen faces. Results - Older and younger adults'
      recognition discriminability did not differ significantly between age groups.
      Notably, the data indicated an own-age bias in young adults, but not in older
      adults, and both age groups' recognition accuracy was greatest for faces that had
      originally been shown with a positive emotional expression. Conclusion - To our
      knowledge, this research is the first to demonstrate an own-age recognition bias
      in younger adults for emotional faces. Although our predictions of a differential
      impact by emotional faces on recognition of same and other-age faces were not
      supported, we identify a number of factors that contextualize these findings in
      the recent literature.

PMID- 30285573
TI  - An application of the theory of normative social behavior to bystander
      intervention for sexual assault.
AB  - OBJECTIVE: Given the high prevalence of sexual assault on U.S. college campuses,
      the current study examines predictors of college students' intentions to
      intervene to prevent sexual assault through the lens of the theory of normative
      social behavior (TNSB). PARTICIPANTS: One hundred eighty-six undergraduate
      students age 18-25 were recruited from an introductory course at a large
      Midwestern university. METHODS: Data were collected through an online survey
      during the 2015-2016 academic year. RESULTS: Results indicated that descriptive
      norms, injunctive norms, and outcome expectations had direct positive effects on
      behavioral intention. However, no direct effect of group identity on intention
      was found. In addition to these main effects, an interaction between descriptive
      and injunctive norms was also observed. CONCLUSIONS: The results of the current
      study speak to theoretical questions surrounding the nature of TNSB variables, as
      well as several practical implications for coordinated efforts to promote
      bystander intervention on college campuses.

PMID- 30285574
TI  - Nutritional Risk among Congregate Meal Site Participants: Benefits of a SNAP-Ed
      Program.
AB  - This study examined the impact of the Supplemental Nutrition Assistance Program
      Education (SNAP-Ed) program Fresh Conversations (FC) on the nutritional risk (NR)
      of older adults (OAs). A convenience sample of OAs (207 Treatment, 148 Control)
      completed questionnaires comprised of validated measures to assess NR, barriers
      to healthy eating self-efficacy (SE), food safety behaviors (FSB), and food
      security (FS) at three-time points over 9 months. Participants were mostly white
      (92.4%), older (age 81+ years, 40.1%), widowed (52.4%), and females (75.2%).
      Independent t-tests identified baseline differences among groups. Analysis of
      covariance assessed group changes at each time point for each measure. Block
      regression determined which variables influence baseline NR. Baseline NR risk was
      significantly predicted by SE (beta = 0.21), education (beta = 0.19) and age
      (beta = 0.14) (p < 0.05). NR improvement was significantly higher for treatment
      group participants who attended four or more FC sessions than for the control
      group (p = .04) when controlling for the effects of gender (p = .061) and SE (p =
      .098).

PMID- 30285575
TI  - Exploring suicide-related disclosure motivation and the impact on mechanisms
      linked to suicide.
AB  - Suicide-related disclosure enables improved risk management but disclosure
      motivations are understudied. This study identified reasons for and against
      disclosing suicidal thoughts and examined their link to future disclosure and
      interpersonal needs among 44 people receiving psychiatric care. The most endorsed
      reasons for disclosure (approach-motivations) included help-seeking, shared
      background, and catharsis. The most endorsed reasons against disclosure
      (avoidance-motivations) included fear of rejection, shame, and hospitalization.
      Higher mean approach motivation was associated with more disclosure intent and
      less burdensomeness. No associations with avoidance motivation were observed.
      Programming that seeks to orient people toward approach motivation holds promise
      for attenuating suicide risk.

PMID- 30285576
TI  - Effectiveness of tacrolimus on IgG4-related disease.

PMID- 30285577
TI  - Contingent Attentional Engagement: Stimulus- and Goal-Driven Capture Have
      Qualitatively Different Consequences.
AB  - We examined whether shifting attention to a location necessarily entails
      extracting the features at that location, a process referred to as attentional
      engagement. In three spatial-cuing experiments ( N = 60), we found that an onset
      cue captured attention both when it shared the target's color and when it did
      not. Yet the effects of the match between the response associated with the cued
      object's identity and the response associated with the target (compatibility
      effects), which are diagnostic of attentional engagement, were observed only with
      relevant-color onset cues. These findings demonstrate that stimulus- and goal
      driven capture have qualitatively different consequences: Before attention is
      reoriented to the target, it is engaged to the location of the critical
      distractor following goal-driven capture but not stimulus-driven capture. The
      reported dissociation between attentional shifts and attentional engagement
      suggests that attention is best described as a camera: One can align its zoom
      lens without pressing the shutter button.

PMID- 30285578
TI  - T-lymphocyte-specific knockout of IKK-2 or NEMO induces Th17 cells in an
      experimental nephrotoxic nephritis mouse model.
AB  - Experimental nephrotoxic serum nephritis (NTN) is a model for T-cell-mediated
      human rapid progressive glomerulonephritis. T-cell receptor stimulation involves
      intracellular signaling events that ultimately lead to the activation of
      transcription factors, such as NF-kappaB. We explored the involvement of the NF
      kappaB components IKK-2 and NEMO in NTN, by using cell-specific knockouts of IKK
      2 and NEMO in CD4+ T lymphocytes. Our results demonstrate that although the
      course of disease was not grossly altered in CD4xIKK2Delta and CD4xNEMODelta
      animals, renal regulatory T cells were significantly reduced and T helper (Th)1
      and Th17 cells significantly increased in both knockout mouse groups. The
      expression of the renal cytokines and chemokines IL-1beta, CCL-2, and CCL-20 was
      also significantly altered in both knockout mice. Lymphocyte transcriptome
      analysis confirmed the increased expression of Th17-related cytokines in spleen
      CD4+ T cells. Moreover, our array data demonstrate an interrupted canonical NF
      kappaB pathway and an increased expression of noncanonical NF-kappaB pathway
      related genes in nephritic CD4xNEMODelta mice, highlighting different downstream
      effects of deletion of IKK-2 or NEMO in T lymphocytes. We propose that better
      understanding of the role of IKK-2 and NEMO in nephritis is essential for the
      clinical application of kinase inhibitors in patients with glomerulonephritis.
      Guo, L., Huang, J., Chen, M., Piotrowski, E., Song, N., Zahner, G., Paust, H.-J.,
      Alawi, M., Geffers, R., Thaiss, F. T-lymphocyte-specific knockout of IKK-2 or
      NEMO induces Th17 cells in an experimental nephrotoxic nephritis mouse model.

PMID- 30285579
TI  - Tomatidine suppresses osteoclastogenesis and mitigates estrogen deficiency
      induced bone mass loss by modulating TRAF6-mediated signaling.
AB  - Postmenopausal osteoporosis is initiated by estrogen withdrawal and is
      characterized mainly by overactivated osteoclastic bone resorption. Targeting TNF
      receptor-associated factor 6 (TRAF6) or its downstream signaling pathways to
      modulate osteoclast formation and function is an appealing strategy for
      osteoclast-related disorders. In the present study, we determined the effect of
      tomatidine, a steroidal alkaloid derived from Solanaceae, on the formation and
      function of receptor activator of NF-kappaB (RANK) ligand-induced osteoclasts and
      the underlying mechanism. Tomatidine inhibited osteoclast formation in a dose
      dependent manner and decreased the expression of osteoclast marker genes. Actin
      ring formation and osteoclastic bone resorption were attenuated in the presence
      of tomatidine in vitro. Eight weeks after ovariectomy, tomatidine prevented
      estrogen deficiency-induced bone loss and restored the mechanical properties of
      the femur. At the molecular level, tomatidine abrogated phosphorylation of c-Jun
      N-terminal kinase (JNK)/p38, NF-kappaB, and protein kinase B (Akt) pathway
      proteins by suppressing RANK expression, inhibiting the binding of TRAF6 to RANK,
      and downregulating the osteoclastogenesis marker-related protein expression. In
      summary, these data demonstrated that tomatidine attenuated osteoclast formation
      and function by modulating multiple TRAF6-mediated pathways. Therefore,
      tomatidine could be a novel candidate for the treatment of osteoclast-related
      disorders, including osteoporosis.-Hu, B., Sun, X., Yang, Y., Ying, Z., Meng, J.,
      Zhou, C., Jiang, G., Li, S., Wu, F., Zhao, X., Zhu, H., Wu, H., Cai, X., Shi, Z.,
      Yan, S. Tomatidine suppresses osteoclastogenesis and mitigates estrogen
      deficiency-induced bone mass loss by modulating TRAF6-mediated signaling.

PMID- 30285580
TI  - Mapping the minimum domain of the fibronectin binding site on transglutaminase 2
      (TG2) and its importance in mediating signaling, adhesion, and migration in TG2
      expressing cells.
AB  - The interaction between the enzyme transglutaminase 2 (TG2) and fibronectin (FN)
      is involved in the cell-matrix interactions that regulate cell signaling,
      adhesion, and migration and play central roles in pathologic conditions,
      particularly fibrosis and cancer. A precise definition of the exact interaction
      domains on both proteins could provide a tool to design novel molecules with
      potential therapeutic applications. Although specific residues involved in the
      interaction within TG2 have been analyzed, little is known regarding the TG2
      binding site on FN. This site has been mapped to a large internal 45-kDa protein
      fragment coincident with the gelatin binding domain (GBD). With the goal of
      defining the minimal FN interacting domain for TG2, we produced several
      expression constructs encoding different portions or modules of the GBD and
      tested their binding and functional properties. The results demonstrate that the
      I8 module is necessary and sufficient for TG2-binding in vitro, but does not have
      functional effects on TG2-expressing cells. Modules I7 and I9 increase the
      strength of the binding and are required for cell adhesion. A 15-kDa fragment
      encompassing modules I7-9 behaves as the whole 45-kDa GBD and mediates signaling,
      adhesion, spreading, and migration of TG2+ cells. This study provides new
      insights into the mechanism for TG2 binding to FN.-Soluri, M. F., Boccafoschi,
      F., Cotella, D., Moro, L., Forestieri, G., Autiero, I., Cavallo, L., Oliva, R.,
      Griffin, M., Wang, Z., Santoro, C., Sblattero, D. Mapping the minimum domain of
      the fibronectin binding site on transglutaminase 2 (TG2) and its importance in
      mediating signaling, adhesion, and migration in TG2-expressing cells.

PMID- 30285581
TI  - Decrease in alphabeta/gammadelta T-cell ratio is accompanied by a reduction in
      high-fat diet-induced weight gain, insulin resistance, and inflammation.
AB  - The implication of alphabeta and gammadelta T cells in obesity-associated
      inflammation and insulin resistance (IR) remains uncertain. Mice lacking
      gammadelta T cells show either no difference or a decrease in high-fat diet (HFD)
      induced IR, whereas partial depletion in gammadelta T cells does not protect from
      HFD-induced IR. alphabeta T-cell deficiency leads to a decrease in white adipose
      tissue (WAT) inflammation and IR without weight change, but partial depletion of
      these cells has not been studied. We previously described a mouse model
      overexpressing peroxisome proliferator-activated receptor beta (PPAR-beta)
      specifically in T cells [transgenic (Tg) T-PPAR-beta] that exhibits a partial
      depletion in alphabeta T cells and no change in gammadelta T-cell number. This
      results in a decreased alphabeta/gammadelta T-cell ratio in lymphoid organs. We
      now show that Tg T-PPAR-beta mice are partially protected against HFD-induced
      weight gain and exhibit decreased IR and liver steatosis independently of animal
      weight. These mice display an alteration of WAT-depots distribution with an
      increased epididymal-WAT mass and a decreased subcutaneous WAT mass. Immune cell
      number is decreased in both WAT-depots, except for gammadelta T cells, which are
      increased in epididymal-WAT. Overall, we show that decreasing
      alphabeta/gammadelta T-cell ratio in WAT-depots alters their inflammatory state
      and mass repartition, which might be involved in improvement of insulin
      sensitivity.-Le Menn, G., Sibille, B., Murdaca, J., Rousseau, A.-S., Squillace,
      R., Vergoni, B., Cormont, M., Niot, I., Grimaldi, P. A., Mothe-Satney, I., Neels,
      J. G. Decrease in alphabeta/gammadelta T-cell ratio is accompanied by a reduction
      in high-fat diet-induced weight gain, insulin resistance, and inflammation.

PMID- 30285582
TI  - KOH modified Thevetia peruviana shell activated carbon for sorption of dimethoate
      from aqueous solution.
AB  - Modified Thevetia peruviana shell activated carbon for sorption of dimethoate
      from aqueous solution derived with potassium hydroxide (KOH) was studied at
      different concentrations for its potential application in water treatment. The
      batch sorption was investigated using dimethoate solution of 10-100 mg/L
      concentrations. Proximate analysis was determined and changes on the surfaces and
      structure of the TPS were characterized after chemical activation with KOH using
      XRD, FTIR, SEM-EDAX, pHpzc, BET. The quantum chemical calculation for dimethoate
      yielded molecule associated energies of -9.8421 (HOMO) and -2.3879 (LUMO) and a
      total energy of -53,376.2. The kinetic of the sorption was modeled which
      indicated the sorption equilibrium time as 90 min and pseudo-first order kinetics
      model showing R2 = 0.994 provided a better description of the process. Analysis
      of sorption equilibrium revealed that the data fitted well to Freundlich sorption
      isotherm model (R2 = 0.966), indicating multi-layer sorption of dimethoate on the
      surface of sorbent. The sorption of dimethoate onto KOHTPS shows 92.60% removal
      efficiency.

PMID- 30285583
TI  - Adverse Childhood Experiences and Healthcare Costs in Adult Life.
AB  - The current study aims to present the prevalence of adverse childhood experiences
      and examine the healthcare costs associated with primary, allied, and specialist
      healthcare services. The Australian Longitudinal Study on Women's Health is a
      general health survey of four nationally representative age cohorts. The current
      study uses 20 years of survey and administrative data (1996-2015) from the cohort
      born 1973-1978. Overall, 41% of women indicated at least one category of
      childhood adversity. The most commonly reported type of childhood adversity was
      having a household member with a mental illness (16%), with the most commonly
      reported ACES category being psychological abuse (17%). Women who had experienced
      adversity in childhood had higher healthcare costs than women who had not
      experienced adversity. The healthcare costs associated with experiences of
      adversity in childhood fully justify a comprehensive policy and practice review.

PMID- 30285584
TI  - Interpersonal theory dimensions facilitate posttraumatic growth among suicide
      loss survivors: An attachment perspective.
AB  - Many studies have highlighted the deleterious psychological impact of suicide on
      bereaved individuals. We examined the psychological processes facilitating
      posttraumatic growth (PTG) among 124 suicide-loss survivors, focusing on
      attachment styles, perceived burdensomeness, and thwarted belongingness. Securely
      attached individuals achieved higher PTG than insecurely attached individuals.
      Perceived burdensomeness and thwarted belongingness both mediated and moderated
      the associations between attachment and PTG. Anxiously or avoidantly attached
      individuals who also had a high level of perceived burdensomeness were the least
      likely to achieve PTG. Thus, these individuals may derive particular benefit from
      attachment-based therapeutic interventions focusing on interpersonal
      relationships.

PMID- 30285585
TI  - Predictive factors for radiographic progression of large joint damage in patients
      with rheumatoid arthritis treated with biological disease-modifying antirheumatic
      drugs (bDMARDs): results of 3 to 4 years of follow-up.
AB  - OBJECTIVES: Little information is available regarding long-term follow-up of
      radiographic progression of damage (RPD) to large joints during treatment of
      rheumatoid arthritis (RA) with biological disease-modifying antirheumatic drugs
      (bDMARDs). We evaluated 3- to 4-year follow-up results and the associations
      between RPD and patient background and Larsen grade (LG) of joints. METHODS:
      Seventy-one RA patients receiving bDMARDs for 3 to 4 years or who achieved bDMARD
      free status were included. The mean age and disease duration at the start of
      bDMARDs were 62.4 years and 10.8 years, respectively. A total of 314 joints,
      including shoulders, elbows, hips, knees, and ankles, were evaluated to determine
      whether RPD was present by comparing radiographs before and after treatment.
      RESULTS: RPD was observed in 24 patients (33.8%) and 34 joints (10.8%). Joints
      with a LG of III or higher had significantly higher rates of RPD than those with
      LGs I and II. Multivariate logistic regression analysis revealed that stage and
      health assessment questionnaire (HAQ) score at 18-month were independent risk
      factors for RPD (cut-off value: 2.5, odds ratio: 7.222 for stage; cut-off value:
      0.9375, odds ratio: 6.278 for HAQ at 18-month). CONCLUSIONS: Stage, HAQ at 18
      month, and LG at the start of bDMARDs were predictive of RPD after 3 to 4 years.
      bDMARDs should be started before both stage and LG exceed III and the therapeutic
      strategy should be determined so that HAQ does not exceed 1.0 during treatment.

PMID- 30285586
TI  - Letter from the editor.

PMID- 30285587
TI  - ISV Congress back to Europe.

PMID- 30285588
TI  - Human Vaccines & Immunotherapeutics: News.

PMID- 30285589
TI  - Analysis of Small Animal Rotating Internship Applicants' Personal Statements.
AB  - The primary purpose of this study was to identify themes that are consistent
      across veterinary internship applicants' personal statements and that are
      correlated with the statements' perceived overall quality. A secondary purpose
      was to investigate the reliability in personal statement quality scoring among
      six experienced internship candidate evaluators. One hundred applications to the
      University of Georgia Small Animal Rotating Internship program were evaluated.
      Each evaluator wrote a description of what he or she values in personal
      statements and his or her beliefs about content and presentation in high- and low
      quality statements. After statement de-identification, each evaluator reviewed 15
      randomly selected personal statements from internship applicants and assigned
      each a score ranging from 1 to 4 according to the following criteria: 1 = would
      not rank for an internship; 2 = would rank in bottom third; 3 = would rank in
      middle third; and 4 = would rank in the top third. A subset of these scored
      personal statements was chosen for qualitative analysis. A qualitative document
      analysis using grounded theory was performed for both the evaluators'
      descriptions of preferences in personal statements and the subset of personal
      statements. Agreement among evaluators' assigned scores was slight (Fleiss's
      kappa = 0.11). Analysis of the evaluator statements and the scored candidate
      statements indicated that important factors in a personal statement include the
      applicant's ability to articulate experiences, to convey maturity, to demonstrate
      understanding of what an internship entails, and to describe reasons for pursuing
      an internship.

PMID- 30285590
TI  - Effect of Different Instructional Methods on Contamination and Personal
      Protective Equipment Protocol Adherence among Veterinary Students.
AB  - Proper use of personal protective equipment (PPE) is crucial to prevent disease
      spread. Recent studies in human medicine have shown disconcerting inconsistencies
      in the use of PPE in hospital wards. In this study, we compared the effect of
      three instructional methods for PPE use on contamination and protocol adherence
      among veterinary students. Students were divided into three groups according to
      the instructional method to which they had access (instructional video, wall
      chart, or both). They underwent an isolation exercise consisting of donning,
      patient examination (mock patient prepared with contamination marker), and
      doffing. Student contamination after the exercise was evaluated using UV light.
      Videos of student performance were reviewed for errors committed. Results showed
      that the number of students with contamination was higher in the group who only
      had access to video instruction than in the two other groups. The number of
      students with contamination on forearms, hands, and wrists was higher in the
      group who only had access to charts. Disinfecting gloves between doffing steps
      was the most frequently omitted step. The number of students who touched the
      environment with unprotected areas of their bodies was higher in the group who
      only had access to video instruction than in the other two groups. In conclusion,
      video instruction was less effective in achieving PPE protocol adherence among
      veterinary students than was instruction with a chart or chart-video combination.
      Incorporating video instruction as part of the instructions may be valuable to
      reinforce individual steps of donning and doffing.

PMID- 30285591
TI  - What are Employers Looking for in New Veterinary Graduates? A Content Analysis of
      UK Veterinary Job Advertisements.
AB  - As veterinary educators, we have a responsibility to ensure that our graduates
      are prepared for working life. Veterinary practices, like any other businesses,
      rely on good employees, and the implications of a poor match between newly
      employed veterinarian and employing practice could be extremely costly in terms
      of personal well-being and enjoyment of work as well as the time, financial, and
      goodwill costs of high staff turnover for the practice. Contemporary veterinary
      curricula encompass a range of teaching to complement the clinical content;
      including communication, teamwork, problem solving, and business skills, to
      support good practice and increase the employability of new graduates. Previous
      studies have examined the qualities required of early career veterinarians as
      viewed by educators, recent graduates, pet owners, and practitioners; however,
      nobody has previously constructed a picture of the employment market for new
      veterinary graduates by exploring the nature of its recruitment advertising.
      Three months of UK veterinary job advertisements were examined. Content analysis
      yielded 10 distinct characteristics desired by employers of early career
      veterinarians. The most common by far was "enthusiasm," followed by an interest
      in a particular area of practice, being an "all-rounder" (i.e., having a broad
      range of skills), demonstrating good communication skills, teamwork, client care,
      and independence, as well as being caring, ambitious, and having high clinical
      standards. While several of these qualities are expected and are specifically
      taught in veterinary school, the dominance of "enthusiasm" as a specifically
      desired trait raises interesting questions about the characteristics of
      veterinary students who we are supporting, encouraging, or maybe even
      suppressing, during veterinary training.

PMID- 30285592
TI  - Evaluating Dog and Cat Owner Preferences for Calgary-Cambridge Communication
      Skills: Results of a Questionnaire.
AB  - Veterinary client retention by companion animal practices is influenced by
      whether the client feels connected to the healthcare provider. Effective
      communication between the veterinarian and the client facilitates that
      connection. To prepare new graduates for success in clinical practice, many
      colleges of veterinary medicine are now incorporating communication into the
      curriculum to emphasize its importance in establishing and maintaining the
      veterinarian-client relationship. A 2016 focus group study by Englar et al.
      evaluated dog and cat owner communication preferences for Calgary-Cambridge Guide
      (CCG) communication skills and concluded that dog and cat owners may have
      different communication needs. This study was conducted to confirm whether
      species-based communication preferences exist among veterinary clients. A
      questionnaire was distributed online and on-site, within veterinary teaching
      hospitals and private practices. Based upon 215 submissions from dog owners and
      166 from cat owners, the communication preferences of dog and cat owners overlap.
      Both dog and cat owners prioritize reflective listening as the most important
      foundational CCG communication skill, and both prioritize asking permission as
      the most important core CCG skill. However, dog owners valued open-ended
      questions more than cat owners, and cat owners valued empathy more than dog
      owners. Survey limitations were largely demographic: participants were
      predominantly female and between the ages of 18-40 years. Survey data may
      therefore not be representative of the perspective of males and/or those >40
      years of age.

PMID- 30285593
TI  - Educators' Perspectives on Animal Welfare and Ethics in the Australia and New
      Zealand Veterinary Curricula.
AB  - The current study was designed to explore the importance that veterinary science
      educators in Australia and New Zealand universities assign to animal welfare and
      ethics (AWE) topics as Day One/Initial Competences for new graduates. An online
      questionnaire was deployed in parallel with an equivalent study of veterinary
      science students at these educators' schools. Responses were received from 142
      educators (51% females n=72 and 49% males n=70), representing an overall
      participation rate of 25%. Questions were clustered according to seven areas of
      veterinary employment: general practice, production animals, companion animals,
      wild animals, aquatic animals, animals kept for scientific purposes, and animals
      used in sport and recreation. The most highly rated topics for each of these
      clusters were: professional ethics in general practice, euthanasia in companion
      animals, strategies to address painful husbandry procedures in production
      animals, veterinarians' duties to wild animals in animals in the wild, aquatic
      animal health and welfare issues in aquatic animals; competence in the 3Rs
      (replacement, refinement and reduction) in animals kept for scientific purposes,
      and responsibilities of ownership in sport and recreation. Female educators rated
      many of the topics as significantly more important than did their male
      counterparts. Educators teaching one or more ethics-related subjects were less
      likely to rate neutering and euthanasia as important as those not teaching these
      subjects. The educators' focus on practical issues clashes with a perceived need
      for veterinarians to actively embrace animal ethics. Overall, the perspectives of
      these educators should be carefully considered as they are likely to influence
      student attitudes.

PMID- 30285594
TI  - Evaluation of Two Training Methods for Teaching the Abdominal Focused Assessment
      with Sonography for Trauma Technique (A-FAST) to First- and Second-Year
      Veterinary Students.
AB  - Ultrasound techniques, including focused assessment with sonography for trauma
      (FAST) examinations, are commonly used in veterinary practice, making inclusion
      of ultrasound in veterinary curricula increasingly important. The best approach
      for teaching ultrasound techniques in veterinary medicine has not been evaluated.
      This study compared the results of two training techniques, live-animal training
      and online video instruction, on students' performance during abdominal FAST (A
      FAST) examinations. Thirty-eight first- and second-year veterinary students were
      randomly assigned to learn A-FAST via a live-animal laboratory or an
      instructional video. The live-animal group received one-on-one instruction in A
      FAST techniques during a single laboratory. The video group received a link to an
      instructional video demonstrating A-FAST techniques, allowing unlimited viewing
      opportunities over a 2-week period. Both groups were also provided written
      instructional information. All participants were assessed on their ability to
      find and correctly name the four A-FAST quadrants on a live animal. We found a
      significant difference between the two groups in the students' ability to
      identify the diaphragmatic-hepatic (DH) view, but for the other three views
      (hepatorenal, splenorenal, and cystocolic), training method did not affect
      performance. Results suggest the potential for using a multi-modal instructional
      approach to teach ultrasound techniques to veterinary students.

PMID- 30285595
TI  - Assessing Differences in Understanding of Companion-Animal Preventive Care
      between a Veterinary Healthcare Team and Pet Owners in a Veterinary Teaching
      Hospital.
AB  - Preventive healthcare visits to primary care veterinary practices in the United
      States have been on the decline over the past decade. One of the main factors
      that has been identified is a lack of understanding by pet owners regarding the
      importance of preventive care. The Partners for Healthy Pets Opportunity Survey
      was adapted for use in this study to determine whether there were differences in
      perceptions of a veterinary healthcare team between team members and clients,
      specifically regarding preventive care within the Community Practice service of
      the Virginia-Maryland College of Veterinary Medicine. Results of this cross
      sectional study revealed that the clients and veterinary healthcare team tended
      to be aligned in most areas regarding companion-animal preventive care. There
      were some specific areas that differed, including a disconnect regarding
      components of feline wellness visits, reliable sources of medical information,
      and strength of recommendations from the veterinary healthcare team. The Partners
      for Healthy Pets Opportunity Survey could be adapted for use in other university
      based companion-animal general-practice teaching environments to better
      understand differences between clients and the veterinary healthcare team
      regarding preventive care and thereby improve educational and service goals of
      primary care veterinary education. Efforts to better understand and mitigate
      potential communication gaps between pet owners and veterinary healthcare teams
      have the potential to improve preventive care not only in university-based
      practice but also in private clinical practice.

PMID- 30285596
TI  - Am I Being Understood? Veterinary Students' Perceptions of the Relationship
      between Their Language Background, Communication Ability, and Clinical Learning.
AB  - During clinical workplace learning, effective communication between veterinary
      students and clinical staff is of paramount importance to facilitating learning,
      assessment, and patient care. Although studies in health sciences education have
      indicated that students may experience communication difficulties as a result of
      linguistic, cultural, and other factors and that these difficulties can affect
      clinical learning and academic outcomes, this has not yet been explored in
      veterinary clinical educational contexts. In this study, the authors sought to
      identify whether final-year veterinary students perceived that their
      communication ability influenced their clinical learning and, if so, whether
      language background was of significance. Seventy-one students from a final-year
      cohort at an Australian veterinary school completed a student perception survey
      at the end of their clinical training. Exploratory factor analysis was used to
      investigate the extent to which learners perceived that their communication
      ability influenced their clinical learning. Two factors explained 72.3% of total
      variance. Factor 1 related to communication ability as a source of concern;
      Factor 2 related to comprehending and contributing to clinical conversations.
      Communication ability as a source of concern differed significantly ( p < .001)
      between students who did and did not have an English-speaking background, but
      there was no significant difference between these two student groups for Factor
      2. Although language background was associated with self-perceived communication
      ability, evidence also emerged that students may experience communication
      challenges during clinical learning, irrespective of their language background.

PMID- 30285597
TI  - Using a Standardized Client Encounter in the Veterinary Curriculum to Practice
      Veterinarian-Employer Discussions about Animal Cruelty Reporting.
AB  - Animal cruelty is the antithesis of animal welfare. Because veterinarians take an
      oath to protect animal welfare, they are professionally obligated to report
      animal cruelty. Several US states have mandatory reporting laws for
      veterinarians, and both the American Veterinary Medical Association (AVMA) and
      the American Animal Hospital Association support reporting. Some state veterinary
      practice acts, such as Arizona's, also require reporting. Despite this, animal
      cruelty is not always emphasized in veterinary curricula. As a result, not all
      veterinary students and graduates feel comfortable recognizing signs of animal
      cruelty and may not be aware of the resources that are available to them when
      considering reporting. AVMA suggests that practices develop their own protocols
      for identifying signs that patients may have been victims of cruelty and
      consulting on cases with senior colleagues with regard to when to report. To
      enhance student comfort with these conversations, Midwestern University College
      of Veterinary Medicine developed a standardized client encounter titled
      "Grizabella's Final Fight." I hope that other colleges of veterinary medicine
      will adapt this teaching tool to allow students the opportunity to practice
      discussions surrounding animal cruelty reporting in the context of state-specific
      legislation that guides their code of professional conduct.

PMID- 30285598
TI  - Tracking Veterinary Students' Acquisition of Communication Skills and Clinical
      Communication Confidence by Comparing Student Performance in the First and Twenty
      Seventh Standardized Client Encounters.
AB  - The American Veterinary Medical Association's Council on Education mandates that
      veterinary students graduate with competence in clinical communication.
      Communication competence facilitates the successful transition of students into
      clinical practice by improving veterinary client satisfaction and reducing the
      risk of litigation. Curricular experimentation with communications training has
      led to innovative approaches to this content area, including the adoption of
      standardized patients from human health care education. Although the use of
      standardized clients (SCs) is time and resource intensive, their use by
      veterinary educators has allowed students to work through authentic cases in a
      safe learning environment in which learner goals drive training. Despite the
      increasing popularity of SC-based communications curricula, outcomes assessment
      studies that track the resultant student growth are lacking. Ninety students in
      the inaugural class of 2018 at Midwestern University College of Veterinary
      Medicine participated in 27 SC encounters over eight consecutive quarters.
      Students' use of Calgary-Cambridge Guide communication skills was compared in the
      first and twenty-seventh encounters. On the basis of SC evaluations of student
      performance, students increased their use of all communication skills in the
      final encounter compared with baseline. Students were also more likely to take a
      comprehensive patient history, build rapport, and retain the client. Mean scores
      for pre- and post-encounter communication confidence, as self-reported by
      students, also increased. These findings support that an SC-rich curriculum
      facilitates student acquisition of communication skills and promotes confidence
      when students approach entry-level clinical tasks such as history taking.

PMID- 30285599
TI  - Exploring the Social Determinants of Animal Health.
AB  - An understanding of the One Health and EcoHealth concepts by students is
      dependent on medical pedagogy and veterinary medical pedagogy having similarities
      that allow a common discourse. Medical pedagogy includes a focus on the social,
      political, and economic forces that affect human health, while this discourse is
      largely absent from veterinary medical pedagogy. There is, however, a gradient in
      health that human and animal populations experience. This health gradient in
      human populations, which runs from low to high according to the World Health
      Organization, is largely explained by "the conditions in which people are born,
      grow, live, work, and age."1,2 Regarding the human health gradient, other authors
      have broadened the list of conditions to include access to health care systems
      used to prevent disease and treat illness, and the distribution of power, money,
      and resources, which are shaped by social, economic, and political forces.1,2 In
      human medicine, these conditions are collectively termed the social determinants
      of health (SDH). Veterinarians who work with the public encounter people and
      their animals at both the low and the high end of the health gradient. This
      article explores the concept of the parallel social determinants of animal health
      (SDAH) using examples within urban, rural, and remote communities in North
      America as well as abroad. We believe that in order to understand the One Health
      paradigm it is imperative that veterinary pedagogy include information on, and
      competence in, SDH and SDAH to ultimately achieve improvements in human, animal,
      and environmental health and wellbeing.

PMID- 30285600
TI  - Qualitative pilot study of veterinarians' perceptions of and experiences with
      counseling about dog walking in companion-animal practice in southern Ontario.
AB  - Dog wal king is beneficial to dogs and their owners, and it supports One Health,
      an initiative devoted to improving the health of animals and humans. Despite the
      benefits of dog walking, many dogs and their owners are not engaging in adequate
      dog-walking exercise. One way to encourage dog walking is for veterinarians to
      counsel owners on dog walking during veterinary appointments. This pilot study
      used individual in-person or telephone interviews to understand veterinarians'
      perceptions of and experiences with counseling about dog walking in companion
      animal practice. Seventeen veterinarians licensed to provide canine care in
      Ontario participated in an interview in 2015. Thematic analysis was used to
      analyze the interview transcripts. Participants thought dog walking was important
      for both dogs and owners and discussed physical, social, and mental benefits of
      dog walking. Participants described barriers to dog-walking counseling including
      dog owners' lack of compliance or physical condition, dogs' behavior, and lack of
      time or low priority during appointments. Also, participants discussed how dog
      walking was not addressed in their professional veterinary education. These
      findings can be used to educate veterinary students and practicing veterinarians
      on the value of dog walking for people and dogs and the barriers they may face
      when counseling clients about dog walking.

PMID- 30285601
TI  - Do criminal associates impact psychiatric inpatients' social support and
      interpersonal needs?
AB  - Suicide risk is elevated among psychiatric inpatients; however, research has not
      examined moderators of the associations between perceived social support and
      thwarted belongingness (TB) and perceived burdensomeness (PB), such as
      involvement with criminal associates. Adult psychiatric inpatients (N = 142)
      completed assessments. Perceived social support was negatively associated with TB
      and PB; however, associates' criminal involvement did not moderate these
      associations. A significant interaction indicated a stronger negative association
      between perceived social support and TB when participants spent more time with
      associates. Therefore, time spent with associates, regardless of criminal
      involvement, may be a relevant interpersonal suicide risk factor.

PMID- 30285602
TI  - Supporting bereaved students at university: Balancing institutional standards and
      reputation alongside individual compassion and care.
AB  - Bereaved university students in the UK are an overlooked population in research,
      policy, and practice. In this article, we examine the implications of this
      neglect via (1) international literature on bereavement in young people; (2)
      international literature on bereavement in higher education students; (3) UK and
      US literature on workplace bereavement and its implications for universities in
      preparing the future workforce; and (4) findings from a scoping study of 90 UK
      universities' bereavement support, which identified no shared comprehensive
      strategy for student bereavement. Our findings show an urgent need for UK
      universities to address this neglect.

PMID- 30285603
TI  - Genome-wide analysis of the rice PPR gene family and their expression profiles
      under different stress treatments.
AB  - BACKGROUND: Pentatricopeptide-repeat proteins (PPRs) are characterized by tandem
      arrays of a degenerate 35-amino-acid (PPR motifs), which can bind RNA strands and
      participate in post-transcription. PPR proteins family is one of the largest
      families in land plants and play important roles in organelle RNA metabolism and
      plant development. However, the functions of PPR genes involved in biotic and
      abiotic stresses of rice (Oryza sativa L.) remain largely unknown. RESULTS: In
      the present study, a comprehensive genome-wide analysis of PPR genes was
      performed. A total of 491 PPR genes were found in the rice genome, of which 246
      PPR genes belong to the P subfamily, and 245 genes belong to the PLS subfamily.
      Gene structure analysis showed that most PPR genes lack intron. Chromosomal
      location analysis indicated that PPR genes were widely distributed in all 12 rice
      chromosomes. Phylogenetic relationship analysis revealed the distinct difference
      between the P and PLS subfamilies. Many PPR proteins are predicted to target
      chloroplasts or mitochondria, and a PPR protein (LOC_Os10g34310) was verified to
      localize in mitochondria. Furthermore, three PPR genes
      (LOC_Os03g17634,LOC_Os07g40820,LOC_Os04g51350) were verified as corresponding
      miRNA targets. The expression pattern analysis showed that many PPR genes could
      be induced under biotic and abiotic stresses. Finally, seven PPR genes were
      confirmed with their expression patterns under salinity or drought stress.
      CONCLUSIONS: We found 491 PPR genes in the rice genome, and our genes structure
      analysis and syntenic analysis indicated that PPR genes might be derived from
      amplification by retro-transposition. The expression pattern present here
      suggested that PPR proteins have crucial roles in response to different abiotic
      stresses in rice. Taken together, our study provides a comprehensive analysis of
      the PPR gene family and will facilitate further studies on their roles in rice
      growth and development.

PMID- 30285604
TI  - MITE Tracker: an accurate approach to identify miniature inverted-repeat
      transposable elements in large genomes.
AB  - BACKGROUND: Miniature inverted-repeat transposable elements (MITEs) are short,
      non-autonomous class II transposable elements present in a high number of
      conserved copies in eukaryote genomes. An accurate identification of these
      elements can help to shed light on the mechanisms controlling genome evolution
      and gene regulation. The structure and distribution of these elements are well
      defined and therefore computational approaches can be used to identify MITEs
      sequences. RESULTS: Here we describe MITE Tracker, a novel, open source software
      program that finds and classifies MITEs using an efficient alignment strategy to
      retrieve nearby inverted-repeat sequences from large genomes. This program groups
      them into high sequence homology families using a fast clustering algorithm and
      finally filters only those elements that were likely transposed from different
      genomic locations because of their low scoring flanking sequence alignment.
      CONCLUSIONS: Many programs have been proposed to find MITEs hidden in genomes.
      However, none of them are able to process large-scale genomes such as that of
      bread wheat. Furthermore, in many cases the existing methods perform high false
      positive rates (or miss rates). The rice genome was used as reference to compare
      MITE Tracker against known tools. Our method turned out to be the most reliable
      in our tests. Indeed, it revealed more known elements, presented the lowest false
      positive number and was the only program able to run with the bread wheat genome
      as input. In wheat, MITE Tracker discovered 6013 MITE families and allowed the
      first structural exploration of MITEs in the complete bread wheat genome.

PMID- 30285605
TI  - The effects of lncRNA MALAT1 on proliferation, invasion and migration in
      colorectal cancer through regulating SOX9.
AB  - BACKGROUND: For the study, we determine the potential biomarkers and uncover the
      regulatory mechanisms of lncRNA MALAT1 / miR-145 / SOX9 axis on the abilities of
      cell growth and cell metastasis of colorectal cancer. METHODS: Previously
      published dataset GSE18105 from GEO database was used for microarray analysis to
      identify differential-expressed lncRNAs and mRNAs. The miRNA which had targeted
      relationships with both lncRNA and mRNA was predicted using miRCode and
      Targetscan. The association between lncRNA and miRNA, miRNA and mRNA was verified
      using dual-luciferase reporter assay. Expression levels of lncRNA MALAT1, miR-145
      and SOX9 were examined by quantitative RT-PCR analysis. The cell viability of two
      cancer cell lines was compared by CCK-8 assay. Colony formation was hired to
      detected cell proliferation. The cell cycle distribution and apoptotic cell rate
      were conducted by flow cytometry assay. Wound healing as well as transwell assay
      were compare the cell migration and cell invasion respectively among groups. The
      effect of MALAT1 on colorectal cancer in vivo was constructed by xenograft model.
      RESULTS: Significantly dysregulated lncRNAs and mRNAs were identified by
      microarray analysis. By experimental verification, MALAT1 and SOX9 were expressed
      in a high percentage of colorectal cancer tumors and cells, while miR-145 was in
      a low expression. We also identified miR-145 as a target of MALAT1 and SOX9.
      MALAT1 played a role in regulating cancer process by functioning as a competing
      endogenous RNA. Silencing MALAT1 could effectively decrease the expression level
      of SOX9, thus suppress cell viability and metastasis. Down-regulated MALAT1 could
      induce resistance of G1 phase in cell cycle, and facilitation of colorectal
      cancer cell apoptosis. Nude mice injected with cells transfected with si-MALAT1
      had smaller tumor on size and weight. CONCLUSIONS: The regulatory function of
      lncRNA MALAT1 / miR-145 / SOX9 axis was revealed in colorectal cancer based on
      bioinformatics analysis. LncRNA MALAT1 could facilitate colorectal cancer cell
      proliferation, invasion and migration by down-regulating miR-145 and up
      regulating SOX9. LncRNA MALAT1 could suppress cell cycle and apoptosis through
      MALAT1 / miR-145 / SOX9 axis.

PMID- 30285606
TI  - Uncovering new disease indications for G-protein coupled receptors and their
      endogenous ligands.
AB  - BACKGROUND: The Open Targets Platform integrates different data sources in order
      to facilitate identification of potential therapeutic drug targets to treat human
      diseases. It currently provides evidence for nearly 2.6 million potential target
      disease pairs. G-protein coupled receptors are a drug target class of high
      interest because of the number of successful drugs being developed against them
      over many years. Here we describe a systematic approach utilizing the Open
      Targets Platform data to uncover and prioritize potential new disease indications
      for the G-protein coupled receptors and their ligands. RESULTS: Utilizing the
      data available in the Open Targets platform, potential G-protein coupled receptor
      and endogenous ligand disease association pairs were systematically identified.
      Intriguing examples such as GPR35 for inflammatory bowel disease and CXCR4 for
      viral infection are used as illustrations of how a systematic approach can aid in
      the prioritization of interesting drug discovery hypotheses. Combining evidences
      for G-protein coupled receptors and their corresponding endogenous peptidergic
      ligands increases confidence and provides supportive evidence for potential new
      target-disease hypotheses. Comparing such hypotheses to the global pharma drug
      discovery pipeline to validate the approach showed that more than 93% of G
      protein coupled receptor-disease pairs with a high overall Open Targets score
      involved receptors with an existing drug discovery program. CONCLUSIONS: The Open
      Targets gene-disease score can be used to prioritize potential G-protein coupled
      receptors-indication hypotheses. In addition, availability of multiple different
      evidence types markedly increases confidence as does combining evidence from
      known receptor-ligand pairs. Comparing the top-ranked hypotheses to the current
      global pharma pipeline serves validation of our approach and identifies and
      prioritizes new therapeutic opportunities.

PMID- 30285608
TI  - A deep learning-based algorithm for 2-D cell segmentation in microscopy images.
AB  - BACKGROUND: Automatic and reliable characterization of cells in cell cultures is
      key to several applications such as cancer research and drug discovery. Given the
      recent advances in light microscopy and the need for accurate and high-throughput
      analysis of cells, automated algorithms have been developed for segmenting and
      analyzing the cells in microscopy images. Nevertheless, accurate, generic and
      robust whole-cell segmentation is still a persisting need to precisely quantify
      its morphological properties, phenotypes and sub-cellular dynamics. RESULTS: We
      present a single-channel whole cell segmentation algorithm. We use markers that
      stain the whole cell, but with less staining in the nucleus, and without using a
      separate nuclear stain. We show the utility of our approach in microscopy images
      of cell cultures in a wide variety of conditions. Our algorithm uses a deep
      learning approach to learn and predict locations of the cells and their nuclei,
      and combines that with thresholding and watershed-based segmentation. We trained
      and validated our approach using different sets of images, containing cells
      stained with various markers and imaged at different magnifications. Our approach
      achieved a 86% similarity to ground truth segmentation when identifying and
      separating cells. CONCLUSIONS: The proposed algorithm is able to automatically
      segment cells from single channel images using a variety of markers and
      magnifications.

PMID- 30285607
TI  - Comparative analysis of cytokinin response factors in Brassica diploids and
      amphidiploids and insights into the evolution of Brassica species.
AB  - BACKGROUND: Cytokinin is a classical phytohormone that plays important roles in
      numerous plant growth and development processes. In plants, cytokinin signals are
      transduced by a two-component system, which involves many genes, including
      cytokinin response factors (CRFs). Although CRFs take vital part in the growth of
      Arabidopsis thaliana and Solanum lycopersicum, little information of the CRFs in
      the Brassica U-triangle species has been known yet. RESULTS: We identified and
      compared 141 CRFs in the diploids and amphidiploids of Brassica species,
      including B. rapa, B. oleracea, B. nigra, B. napus, and B. juncea. For all the
      141 CRFs, the sequence and structure analysis, physiological and biochemical
      characteristics analysis were performed. Meanwhile, the Ka/Ks ratios of
      orthologous and paralogous gene pairs were calculated, which indicated the
      natural selective pressure upon the overall length or a certain part of the CRFs.
      The expression profiles of CRFs in different tissues and under various stresses
      were analyzed in B. oleracea, B. nigra, and B. napus. The similarities and
      differences in gene sequences and expression profiles among the homologous genes
      of these species were discussed. In addition, AtCRF11 and its ortholog BrCRF11a
      were identified to be related to primary root growth in Arabidopsis. CONCLUSION:
      This study performed a genome-wide comparative analysis of the CRFs in the
      diploids and amphidiploids of the Brassica U-triangle species. Many similarities
      and differences in gene sequences and expression profiles existed among the CRF
      homologous genes of these species. In the bioinformatics analysis, we found the
      close relativity of the CRF homologous genes in the Brassica A and C genomes and
      the distinctiveness of those in the B genome, and the CRF homologous genes in B
      subgenome were considerably influenced by the A subgenome of B. juncea. In
      addition, we identified a new function of the Clade V CRFs related to root
      growth, which also clarified the functional conservation between Arabidopsis and
      B. rapa. These results not only offer useful information on the functional
      analysis of CRFs but also provide new insights into the evolution of Brassica
      species.

PMID- 30285609
TI  - Effect of pulsed transcranial ultrasound stimulation at different number of tone
      burst on cortico-muscular coupling.
AB  - BACKGROUND: Pulsed transcranial ultrasound stimulation (pTUS) can modulate the
      neuronal activity of motor cortex and elicit muscle contractions. Cortico
      muscular coupling (CMC) can serve as a tool to identify interaction between the
      oscillatory activity of the motor cortex and effector muscle. This research aims
      to explore the neuromodulatory effect of low-intensity, pTUS with different
      number of tone burst to neural circuit of motor-control system by analyzing the
      coupling relationship between motor cortex and tail muscle in mouse. The motor
      cortex of mice was stimulated by pulsed transcranial ultrasound with different
      number of tone bursts (NTB = 100 150 200 250 300). The local field potentials
      (LFPs) in tail motor cortex and electromyography (EMG) in tail muscles were
      recorded simultaneously during pTUS. The change of integral coupling strength
      between cortex and muscle was evaluated by mutual information (MI). The
      directional information interaction between them were analyzed by transfer
      entropy (TE). RESULTS: Almost all of the MI and TE values were significantly
      increased by pTUS. The results of MI showed that the CMC was significantly
      enhanced with the increase of NTB. The TE results showed the coupling strength of
      CMC in descending direction (from LFPs to EMG) was significantly higher than that
      in ascending direction (from EMG to LFPs) after stimulation. Furthermore,
      compared to NTB = 100, the CMC in ascending direction were significantly enhanced
      when NTB = 250, 300, and CMC in descending direction were significantly enhanced
      when NTB = 200, 250, 300. CONCLUSION: These results confirm that the CMC between
      motor cortex and the tail muscles in mouse could be altered by pTUS. And by
      increasing the NTB (i.e. sonication duration), the coupling strength within the
      cortico-muscular circuit could be increased, which might further influence the
      motor function of mice. It demonstrates that, using MI and TE method, the CMC
      could be used for quantitatively evaluating the effect of pTUS with different
      NTBs, which might provide a new insight into the effect of pTUS neuromodulation
      in motor cortex.

PMID- 30285610
TI  - High-throughput proteomic profiling of the fish liver following bacterial
      infection.
AB  - BACKGROUND: High-throughput proteomics was used to determine the role of the fish
      liver in defense responses to bacterial infection. This was done using a rainbow
      trout (Oncorhynchus mykiss) model following infection with Aeromonas salmonicida,
      the causative agent of furunculosis. The vertebrate liver has multifaceted
      functions in innate immunity, metabolism, and growth; we hypothesize this tissue
      serves a dual role in supporting host defense in parallel to metabolic
      adjustments that promote effective immune function. While past studies have
      reported mRNA responses to A. salmonicida in salmonids, the impact of bacterial
      infection on the liver proteome remains uncharacterized in fish. RESULTS: Rainbow
      trout were injected with A. salmonicida or PBS (control) and liver extracted 48 h
      later for analysis on a hybrid quadrupole-Orbitrap mass spectrometer. A label
      free method was used for protein abundance profiling, which revealed a strong
      innate immune response along with evidence to support parallel rewiring of
      metabolic and growth systems. 3076 proteins were initially identified against all
      proteins (n = 71,293 RefSeq proteins) annotated in a single high-quality rainbow
      trout reference genome, of which 2433 were maintained for analysis post-quality
      filtering. Among the 2433 proteins, 109 showed significant differential abundance
      following A. salmonicida challenge, including many upregulated complement system
      and acute phase response proteins, in addition to molecules with putative
      functions that may support metabolic re-adjustments. We also identified novel
      expansions in the complement system due to gene and whole genome duplication
      events in salmonid evolutionary history, including eight C3 proteins showing
      differential changes in abundance. CONCLUSIONS: This study provides the first
      high-throughput proteomic examination of the fish liver in response to bacterial
      challenge, revealing novel markers for the host defense response, and evidence of
      metabolic remodeling in conjunction with activation of innate immunity.

PMID- 30285611
TI  - Genome-wide survey of potato MADS-box genes reveals that StMADS1 and StMADS13 are
      putative downstream targets of tuberigen StSP6A.
AB  - BACKGROUND: MADS-box genes encode transcription factors that are known to be
      involved in several aspects of plant growth and development, especially in floral
      organ specification. To date, the comprehensive analysis of potato MADS-box gene
      family is still lacking after the completion of potato genome sequencing. A
      genome-wide characterization, classification, and expression analysis of MADS-box
      transcription factor gene family was performed in this study. RESULTS: A total of
      153 MADS-box genes were identified and categorized into MIKC subfamily (MIKCC and
      MIKC*) and M-type subfamily (Malpha, Mbeta, and Mgamma) based on their
      phylogenetic relationships to the Arabidopsis and rice MADS-box genes. The potato
      M-type subfamily had 114 members, which is almost three times of the MIKC members
      (39), indicating that M-type MADS-box genes have a higher duplication rate and/or
      a lower loss rate during potato genome evolution. Potato MADS-box genes were
      present on all 12 potato chromosomes with substantial clustering that mainly
      contributed by the M-type members. Chromosomal localization of potato MADS-box
      genes revealed that MADS-box genes, mostly MIKC, were located on the duplicated
      segments of the potato genome whereas tandem duplications mainly contributed to
      the M-type gene expansion. The potato MIKC subfamily could be further classified
      into 11 subgroups and the TT16-like, AGL17-like, and FLC-like subgroups found in
      Arabidopsis were absent in potato. Moreover, the expressions of potato MADS-box
      genes in various tissues were analyzed by using RNA-seq data and verified by
      quantitative real-time PCR, revealing that the MIKCC genes were mainly expressed
      in flower organs and several of them were highly expressed in stolon and tubers.
      StMADS1 and StMADS13 were up-regulated in the StSP6A-overexpression plants and
      down-regulated in the StSP6A-RNAi plant, and their expression in leaves and/or
      young tubers were associated with high level expression of StSP6A. CONCLUSION:
      Our study identifies the family members of potato MADS-box genes and investigate
      the evolution history and functional divergence of MADS-box gene family.
      Moreover, we analyze the MIKCC expression patterns and screen for genes involved
      in tuberization. Finally, the StMADS1 and StMADS13 are most likely to be
      downstream target of StSP6A and involved in tuber development.

PMID- 30285613
TI  - Investigating the frequency of triploid Atlantic salmon in wild Norwegian and
      Russian populations.
AB  - BACKGROUND: Fish may display variations in ploidy, including three sets of
      chromosomes, known as triploidy. A recent study revealed a frequency of ~ 2%
      spontaneous (i.e., non-intentional) triploidy in domesticated Atlantic salmon
      produced in Norwegian aquaculture in the period 2007-2014. In contrast, the
      frequency of triploidy in wild salmon populations has not been studied thus far,
      and in wild populations of other organisms, it has been very rarely studied. In
      population genetic data sets, individuals that potentially display chromosome
      abnormalities, such as triploids with three alleles, are typically excluded on
      the premise that they may reflect polluted or otherwise compromised samples.
      Here, we critically re-investigated the microsatellite genetic profile of ~ 6000
      wild Atlantic salmon sampled from 80 rivers in Norway and Russia, to investigate
      the frequency of triploid individuals in wild salmon populations for the first
      time. RESULTS: We detected a single triploid salmon, and five individuals
      displaying three alleles at one of the loci, thus regarded as putatively
      trisomic. This gave an overall frequency of triploid and putatively trisomic
      individuals in the data set of 0.017 and 0.083% respectively. The triploid salmon
      was an adult female, and had spent 2 years in freshwater and 2 years in the sea.
      CONCLUSIONS: We conclude that the frequency of naturally-occurring triploid
      Atlantic salmon in wild Norwegian and Russian populations is very low, and many
      fold lower than the frequency of spontaneous triploids observed in aquaculture.
      Our results suggest that aquaculture rearing conditions substantially increase
      the probability of triploidy to develop, and/or permits greater survival of
      triploid individuals, in comparison to the wild.

PMID- 30285612
TI  - Environmental pH modulates transcriptomic responses in the fungus Fusarium sp.
      associated with KSHB Euwallacea sp. near fornicatus.
AB  - BACKGROUND: The Ambrosia Fusarium Clade phytopathogenic Fusarium fungi species
      have a symbiotic relationship with ambrosia beetles in the genus Euwallacea
      (Coleoptera: Curculionidae). Related beetle species referred to as Euwallacea sp.
      near fornicatus have been spread in California, USA and are recognized as the
      causal agents of Fusarium dieback, a disease that causes mortality of many plant
      species. Despite the importance of this fungi, no transcriptomic resources have
      been generated. The datasets described here represent the first ever transcripts
      available for these species. We focused our study on the isolated species of
      Fusarium that is associated with one of the cryptic species referred to as
      Kuroshio Shot Hole Borer (KSHB) Euwallacea sp. near fornicatus. RESULTS: Hydrogen
      concentration is a critical signal in fungi for growth and host colonization, the
      aim of this study was to evaluate the effect of different pH conditions on growth
      and gene expression of the fungus Fusarium sp. associated with KSHB. An RNA-seq
      approach was used to compare the gene expression of the fungus grown for 2 weeks
      in liquid medium at three different pH levels (5.0, 6.0, and 7.0). An unbuffered
      treatment was included to evaluate the capability of the fungus to change the pH
      of its environment and the impact in gene expression. The results showed that the
      fungus can grow and modulate its genetic expression at different pH conditions;
      however, growth was stunted in acidic pH in comparison with neutral pH. The
      results showed a differential expression pattern in each pH condition even when
      acidic conditions prevailed at the end of the experiment. After comparing
      transcriptomics data from the three treatments, we found a total of 4,943 unique
      transcripts that were differentially expressed. CONCLUSIONS: We identified
      transcripts related to pH signaling such as the conserved PAL/RIM pathway, some
      transcripts related to secondary metabolism and other transcripts that were
      differentially expressed. Our analysis suggests possible mechanisms involved in
      pathogenicity in this novel Fusarium species. This is the first report that shows
      transcriptomic data of this pathogen as well as the first report of genes and
      proteins involved in their metabolism identifying potential virulence factors.

PMID- 30285616
TI  - Correction to: MoMyb1 is required for asexual development and tissue-specific
      infection in the rice blast fungus Magnaporthe oryzae.
AB  - Following the publication of this article [1], the authors noticed that they
      mistakenly introduced duplicate images in Figure 6A during the preparation of
      figures. They apologize for any confusion that brought to the readers and have
      corrected the figure. This correction does not change any statement or conclusion
      drawn from the data.

PMID- 30285615
TI  - Transcriptome sequencing of Pinus kesiya var. langbianensis and comparative
      analysis in the Pinus phylogeny.
AB  - BACKGROUND: Pines are widely distributed in the Northern Hemisphere and have a
      long evolutionary history. The availability of transcriptome data has facilitated
      comparative transcriptomics for studying the evolutionary patterns associated
      with the different geographical distributions of species in the Pinus phylogeny.
      RESULTS: The transcriptome of Pinus kesiya var. langbianensis was sequenced using
      the Illumina HiSeq 2000 platform, and a total of 68,881 unigenes were assembled
      by Trinity. Transcriptome sequences of another 12 conifer species were downloaded
      from public databases. All of the pairwise orthologues were identified by
      comparative transcriptome analysis in 13 conifer species, from which the rate of
      diversification was calculated and a phylogenetic tree inferred. All of the fast
      evolving positive selection sequences were identified, and some salt-, drought-,
      and abscisic acid-resistance genes were discovered. CONCLUSIONS: mRNA sequences
      of P. kesiya var. langbianensis were obtained by transcriptome sequencing, and a
      large number of simple sequence repeat and short nucleotide polymorphism loci
      were detected. These data can be used in molecular marker-assisted selected in
      pine breeding. Divergence times were estimated in the 13 conifer species using
      comparative transcriptomic analysis. A number of positive selection genes were
      found to be related to environmental factors. Salt- and abscisic acid-related
      genes exhibited different selection patterns between coastal and inland Pinus.
      Our findings help elucidate speciation patterns in the Pinus lineage.

PMID- 30285614
TI  - Genome wide identification and predicted functional analyses of NAC transcription
      factors in Asian pears.
AB  - BACKGROUND: NAC proteins contribute to diverse plant developmental processes as
      well as tolerances to biotic and abiotic stresses. The pear genome had been
      decoded and provided the basis for the genome-wide analysis to find the
      evolution, duplication, gene structures and predicted functions of PpNAC
      transcription factors. RESULTS: A total of 185 PpNAC genes were found in pear, of
      which 148 were mapped on chromosomes while 37 were on unanchored scaffolds.
      Phylogeny split the NAC genes into 6 clades (Group1- Group6) with their sub
      clades (~ subgroup A to subgroup H) and each group displayed common motifs with
      no/minor change. The numbers of exons in each group varied from 1 to 12 with an
      average of 3 while 44 pairs from all groups showed their duplication events. qPCR
      and RNA-Seq data analyses in different pear cultivars/species revealed some
      predicted functions of PpNAC genes i.e. PpNACs 37, 61, 70 (2A), 53, 151(2D), 10,
      92, 130 and 154 (3D) were potentially involved in bud endodormancy, PpNACs 61, 70
      (2A), 172, 176 and 23 (4E) were associated with fruit pigmentations in blue
      light, PpNACs 127 (1E), 46 (1G) and 56 (5A) might be related to early, middle and
      late fruit developments respectively. Besides, all genes from subgroups 2D and 3D
      were found to be related with abiotic stress (cold, salt and drought) tolerances
      by targeting the stress responsive genes in pear. CONCLUSIONS: The present genome
      wide analysis provided valuable information for understanding the classification,
      motif and gene structure, evolution and predicted functions of NAC gene family in
      pear as well as in higher plants. NAC TFs play diverse and multifunctional roles
      in biotic and abiotic stresses, growth and development and fruit ripening and
      pigmentation through multiple pathways in pear.

PMID- 30285617
TI  - Combining controls can improve power in two-stage association studies.
AB  - BACKGROUND: High dimensional case control studies are ubiquitous in the
      biological sciences, particularly genomics. To maximise power while constraining
      cost and to minimise type-1 error rates, researchers typically seek to replicate
      findings in a second experiment on independent cohorts before proceeding with
      further analyses. This can be an expensive procedure, particularly when control
      samples are difficult to recruit or ascertain; for example in inter-disease
      comparisons, or studies on degenerative diseases. RESULTS: This paper presents a
      method in which control (or case) samples from the discovery cohort are re-used
      in a replication study. The theoretical implications of this method are discussed
      and simulated genome-wide association study (GWAS) tests are used to compare
      performance against the standard approach in a range of circumstances. Using
      similar methods, a procedure is proposed for 'partial replication' using a new
      independent cohort consisting of only controls. This methods can be used to
      provide some validation of findings when a full replication procedure is not
      possible. The new method has differing sensitivity to confounding in study
      cohorts compared to the standard procedure, which must be considered in its
      application. Type-1 error rates in these scenarios are analytically and
      empirically derived, and an online tool for comparing power and error rates is
      provided. CONCLUSIONS: In several common study designs, a shared-control method
      allows a substantial improvement in power while retaining type-1 error rate
      control. Although careful consideration must be made of all necessary
      assumptions, this method can enable more efficient use of data in GWAS and other
      applications.

PMID- 30285618
TI  - A Lotus japonicus E3 ligase interacts with the Nod Factor Receptor 5 and
      positively regulates nodulation.
AB  - BACKGROUND: Post-translational modification of receptor proteins is involved in
      activation and de-activation of signalling systems in plants. Both ubiquitination
      and deubiquitination have been implicated in plant interactions with pathogens
      and symbionts. RESULTS: Here we present LjPUB13, a PUB-ARMADILLO repeat E3 ligase
      that specifically ubiquitinates the kinase domain of the Nod Factor receptor NFR5
      and has a direct role in nodule organogenesis events in Lotus japonicus.
      Phenotypic analyses of three LORE1 retroelement insertion plant lines revealed
      that pub13 plants display delayed and reduced nodulation capacity and retarded
      growth. LjPUB13 expression is spatially regulated during symbiosis with
      Mesorhizobium loti, with increased levels in young developing nodules.
      CONCLUSION: LjPUB13 is an E3 ligase with a positive regulatory role during the
      initial stages of nodulation in L. japonicus.

PMID- 30285619
TI  - Integration of small RNAs and transcriptome sequencing uncovers a complex
      regulatory network during vernalization and heading stages of orchardgrass
      (Dactylis glomerata L.).
AB  - BACKGROUND: Flowering is a critical reproductive process in higher plants. Timing
      of optimal flowering depends upon the coordination among seasonal environmental
      cues. For cool season grasses, such as Dactylis glomerata, vernalization induced
      by low temperature provides competence to initiate flowering after prolonged
      cold. We combined analyses of the transcriptome and microRNAs (miRNAs) to
      generate a comprehensive resource for regulatory miRNAs and their target circuits
      during vernalization and heading stages. RESULTS: A total of 3,846 differentially
      expressed genes (DEGs) and 69 differentially expressed miRNAs were identified
      across five flowering stages. The expression of miR395, miR530, miR167, miR396,
      miR528, novel_42, novel_72, novel_107, and novel_123 demonstrated significant
      variations during vernalization. These miRNA targeted genes were involved in
      phytohormones, transmembrane transport, and plant morphogenesis in response to
      vernalization. The expression patterns of DEGs related to plant hormones, stress
      responses, energy metabolism, and signal transduction changed significantly in
      the transition from vegetative to reproductive phases. CONCLUSIONS: Five hub
      genes, c136110_g1 (BRI1), c131375_g1 (BZR1), c133350_g1 (VRN1), c139830_g1
      (VIN3), and c125792_g2 (FT), might play central roles in vernalization response.
      Our comprehensive analyses have provided a useful platform for investigating
      consecutive transcriptional and post-transcriptional regulation of critical
      phases in D. glomerata and provided insights into the genetic engineering of
      flowering-control in cereal crops.

PMID- 30285620
TI  - Exclusivity offers a sound yet practical species criterion for bacteria despite
      abundant gene flow.
AB  - BACKGROUND: The question of whether bacterial species objectively exist has long
      divided microbiologists. A major source of contention stems from the fact that
      bacteria regularly engage in horizontal gene transfer (HGT), making it difficult
      to ascertain relatedness and draw boundaries between taxa. A natural way to
      define taxa is based on exclusivity of relatedness, which applies when members of
      a taxon are more closely related to each other than they are to any outsider. It
      is largely unknown whether exclusive bacterial taxa exist when averaging over the
      genome or are rare due to rampant hybridization. RESULTS: Here, we analyze a
      collection of 701 genomes representing a wide variety of environmental isolates
      from the family Streptomycetaceae, whose members are competent at HGT. We find
      that the presence/absence of auxiliary genes in the pan-genome displays a
      hierarchical (tree-like) structure that correlates significantly with the
      genealogy of the core-genome. Moreover, we identified the existence of many
      exclusive taxa, although individual genes often contradict these taxa. These
      conclusions were supported by repeating the analysis on 1,586 genomes belonging
      to the genus Bacillus. However, despite confirming the existence of exclusive
      groups (taxa), we were unable to identify an objective threshold at which to
      assign the rank of species. CONCLUSIONS: The existence of bacterial taxa is
      justified by considering average relatedness across the entire genome, as
      captured by exclusivity, but is rejected if one requires unanimous agreement of
      all parts of the genome. We propose using exclusivity to delimit taxa and
      conventional genome similarity thresholds to assign bacterial taxa to the species
      rank. This approach recognizes species that are phylogenetically meaningful,
      while also establishing some degree of comparability across species-ranked taxa
      in different bacterial clades.

PMID- 30285621
TI  - Bead-linked transposomes enable a normalization-free workflow for NGS library
      preparation.
AB  - BACKGROUND: Transposome-based technologies have enabled the streamlined
      production of sequencer-ready DNA libraries; however, current methods are highly
      sensitive to the amount and quality of input nucleic acid. RESULTS: We describe a
      new library preparation technology (Nextera DNA Flex) that utilizes a known
      concentration of transposomes conjugated directly to beads to bind a fixed amount
      of DNA, and enables direct input of blood and saliva using an integrated
      extraction protocol. We further report results from libraries generated outside
      the standard parameters of the workflow, highlighting novel applications for
      Nextera DNA Flex, including human genome builds and variant calling from below 1
      ng DNA input, customization of insert size, and preparation of libraries from
      short fragments and severely degraded FFPE samples. Using this bead-linked
      library preparation method, library yield saturation was observed at an input
      amount of 100 ng. Preparation of libraries from a range of species with varying
      GC levels demonstrated uniform coverage of small genomes. For large and complex
      genomes, coverage across the genome, including difficult regions, was improved
      compared with other library preparation methods. Libraries were successfully
      generated from amplicons of varying sizes (from 50 bp to 11 kb), however, a
      decrease in efficiency was observed for amplicons smaller than 250 bp. This
      library preparation method was also compatible with poor-quality DNA samples,
      with sequenceable libraries prepared from formalin-fixed paraffin-embedded
      samples with varying levels of degradation. CONCLUSIONS: In contrast to solution
      based library preparation, this bead-based technology produces a normalized,
      sequencing-ready library for a wide range of DNA input types and amounts, largely
      obviating the need for DNA quantitation. The robustness of this bead-based
      library preparation kit and flexibility of input DNA facilitates application
      across a wide range of fields.

PMID- 30285622
TI  - The rare orange-red colored Euphorbia pulcherrima cultivar 'Harvest Orange' shows
      a nonsense mutation in a flavonoid 3'-hydroxylase allele expressed in the bracts.
AB  - BACKGROUND: Commercially available poinsettia (Euphorbia pulcherrima) varieties
      prevalently accumulate cyanidin derivatives and show intense red coloration.
      Orange-red bract color is less common. We investigated four cultivars displaying
      four different red hues with respect to selected enzymes and genes of the
      anthocyanin pathway, putatively determining the color hue. RESULTS: Red hues
      correlated with anthocyanin composition and concentration and showed common dark
      red coloration in cultivars 'Christmas Beauty' and 'Christmas Feeling' where
      cyanidin derivatives were prevalent. In contrast, orange-red bract color is based
      on the prevalent presence of pelargonidin derivatives that comprised 85% of the
      total anthocyanin content in cv. 'Premium Red' and 96% in cv. 'Harvest Orange'
      (synonym: 'Orange Spice'). cDNA clones of flavonoid 3'-hydroxylase (F3'H) and
      dihydroflavonol 4-reductase (DFR) were isolated from the four varieties, and
      functional activity and substrate specificity of the corresponding recombinant
      enzymes were studied. Kinetic studies demonstrated that poinsettia DFRs prefer
      dihydromyricetin and dihydroquercetin over dihydrokaempferol, and thus, favor the
      formation of cyanidin over pelargonidin. Whereas the F3'H cDNA clones of
      cultivars 'Christmas Beauty', 'Christmas Feeling', and 'Premium Red' encoded
      functionally active enzymes, the F3'H cDNA clone of cv. 'Harvest Orange'
      contained an insertion of 28 bases, which is partly a duplication of 20 bases
      found close to the insertion site. This causes a frameshift mutation with a
      premature stop codon after nucleotide 132 and, therefore, a non-functional
      enzyme. Heterozygosity of the F3'H was demonstrated in this cultivar, but only
      the mutated allele was expressed in the bracts. No correlation between F3'H
      expression and the color hue could be observed in the four species. CONCLUSIONS:
      Rare orange-red poinsettia hues caused by pelargonidin based anthocyanins can be
      achieved by different mechanisms. F3'H is a critical step in the establishment of
      orange red poinsettia color. Although poinsettia DFR shows a low substrate
      specificity for dihydrokaempferol, sufficient precursor for pelargonidin
      formation is available in planta, in the absence of F3'H activity.

PMID- 30285623
TI  - Skin cancer risk perception and sun protection behavior at work, at leisure, and
      on sun holidays: a survey for Danish outdoor and indoor workers.
AB  - BACKGROUND: To prevent occupational skin cancer, it is essential that the sun
      protective behavior of outdoor workers is adequate. The aim is to study the sun
      protective behavior of Danish outdoor workers at work, at leisure, and on sun
      holiday and compare it to that of indoor workers. METHODS: This is a cross
      sectional study, based on a 53-item survey completed by Danish outdoor (n = 380)
      and indoor workers (n = 119) in 2016-2017. Status as outdoor or indoor worker was
      decided based on self-report and behavioral differences were tested using
      (paired) t tests and multiple regression adjusted for age, sex, educational
      level, history of smoking, and skin type. RESULTS: Danish outdoor workers at work
      use sun protection less than they do at leisure and on sun holiday (alpha < .05)
      where their sun protection behavior is similar to that of indoor workers. The
      proportion of Danish outdoor workers that always/often use sun protection at work
      is for shade seeking around noon 4.2%, sunscreen 34.5%, wide-brimmed hat 25.3%,
      and long trousers and shirt with sleeves 42.4%. Of Danish outdoor workers, 49.5%
      do not think about the risk of occupational skin cancer and 11.8% think the risk
      is insignificant, 32.4% think that the use of sun protection is of low or no
      importance, 84.2% consider sunburn important as skin cancer risk factor still
      88.9% have a history of sunburn at work, > 80.0% agree that risk of skin cancer
      is reduced by the use of sun protection, and only 4.0% dismiss the possibility of
      sun protection use at work. CONCLUSIONS: Skin cancer risk and use of sun
      protection at work are largely neglected in Danish outdoor workers, more so than
      at leisure and on sun holiday where their risk behavior resembles that of indoor
      workers. This indicates an untapped workplace preventive potential.

PMID- 30285624
TI  - Efficient generation of stable, heritable gene edits in wheat using CRISPR/Cas9.
AB  - BACKGROUND: The use of CRISPR/Cas9 systems could prove to be a valuable tool in
      crop research, providing the ability to fully knockout gene function in complex
      genomes or to precisely adjust gene function by knockout of individual alleles.
      RESULTS: We compare gene editing in hexaploid wheat (Triticum aestivum) with
      diploid barley (Hordeum vulgare), using a combination of single genome and tri
      genome targeting. High efficiency gene editing, 11-17% for single genome targeted
      guides and 5% for tri-genome targeted guides, was achieved in wheat using stable
      Agrobacterium-mediated transformation. Gene editing in wheat was shown to be
      predominantly heterozygous, edits were inherited in a Mendelian fashion over
      multiple generations and no off-target effects were observed. Comparison of
      editing between the two species demonstrated that more stable, heritable edits
      were produced in wheat, whilst barley exhibited continued and somatic editing.
      CONCLUSION: Our work shows the potential to obtain stable edited transgene-free
      wheat lines in 36 weeks through only two generations and that targeted
      mutagenesis of individual homeologues within the wheat genome is achievable with
      a modest amount of effort, and without off-target mutations or the need for
      lengthy crossing strategies.

PMID- 30285625
TI  - Air and waterborne microbiome of a pharmaceutical plant provide insights on
      spatiotemporal variations and community resilience after disturbance.
AB  - BACKGROUND: The presence of microrganisms in pharmaceutical production plant
      environments is typically monitored by cultural methods, however these cannot
      detect the unculturable fraction of the microbial community. To get more accurate
      information on the composition of these indoor microbial communities, both water
      and air microbiome from a pharmaceutical production plant were profiled by 16S
      amplicon sequencing. RESULTS: In the water system, we found taxa which typically
      characterize surface freshwater, groundwater and oligotrophic environments. The
      airborne microbiome resulted dominated by taxa usually found in outdoor air in
      combination with human-associated taxa. The alpha- and beta- diversity values
      showed that the heat-based sanitization process of the water plant affects the
      composition of the water microbiome by transiently increasing both diversity and
      evenness. Taxonomic compositional shifts were also detected in response to
      sanitization, consisting in an increase of Firmicutes and alpha-Proteobacteria.
      On the other hand, seasonality seems to be the main driver of bacterial community
      composition in air of this work environment. CONCLUSIONS: This approach resulted
      useful to describe the taxonomy of these indoor microbiomes and could be further
      applied to other built environments, in which the knowledge of the microbiome
      composition is of relevance. In addition, this study could assist in the design
      of new guidelines to improve microbiological quality control in indoor work
      environments.

PMID- 30285626
TI  - Environmentally-driven gene content convergence and the Bacillus phylogeny.
AB  - BACKGROUND: Members of the Bacillus genus have been isolated from a variety of
      environments. However, the relationship between potential metabolism and the
      niche from which bacteria of this genus have been isolated has not been
      extensively studied. The existence of a monophyletic aquatic Bacillus group,
      composed of members isolated from both marine and fresh water has been proposed.
      Here, we present a phylogenetic/phylogenomic analysis to investigate the
      potential relationship between the environment from which group members have been
      isolated and their evolutionary origin. We also carried out hierarchical
      clustering based on functional content to test for potential environmental
      effects on the genetic content of these bacteria. RESULTS: The phylogenetic
      reconstruction showed that Bacillus strains classified as aquatic have
      evolutionary origins in different lineages. Although we observed the presence of
      a clade consisting exclusively of aquatic Bacillus, it is not comprised of the
      same strains previously reported. In contrast to phylogeny, clustering based on
      the functional categories of the encoded proteomes resulted in groups more
      compatible with the environments from which the organisms were isolated. This
      evidence suggests a detectable environmental influence on bacterial genetic
      content, despite their different evolutionary origins. CONCLUSION: Our results
      suggest that aquatic Bacillus species have polyphyletic origins, but exhibit
      convergence at the gene content level.

PMID- 30285627
TI  - Non-invasive cardiac output measurement with electrical velocimetry in patients
      undergoing liver transplantation: comparison of an invasive method with pulmonary
      thermodilution.
AB  - BACKGROUND: The goal of this study was to evaluate the accuracy and
      interchangeability between continuous cardiac output (CO) measured by electrical
      velocimetry (COEv) and continuous cardiac output obtained using the pulmonary
      thermodilution method (COPAC) during living donor liver transplantation (LDLT).
      METHOD: Twenty-three patients were enrolled in this prospective observational
      study. CO was recorded by both two methods and compared at nine specific time
      points. The data were analyzed using correlation coefficients, Bland-Altman
      analysis for the percentage errors, and the concordance rate for trend analysis
      using a four-quadrant plot. RESULTS: In total, 207 paired datasets were recorded
      during LDLT. CO data were in the range of 2.8-12.7 L/min measured by PAC and 3.4
      14.9 L/min derived from the EV machine. The correction coefficient between COPAC
      and COEv was 0.415 with p < 0.01. The 95% limitation agreement was - 5.9 to 3.4
      L/min and the percentage error was 60%. The concordance rate was 56.5%.
      CONCLUSIONS: The AesculonTM monitor is not yet interchangeable with continuous
      thermodilution CO monitoring during LDLT. TRIAL REGISTRATION: The study was
      approved by the Institutional Review Board of Chang Gung Medical Foundation in
      Taiwan (registration number: 201600264B0 ).

PMID- 30285628
TI  - Transcriptomic response to parasite infection in Nile tilapia (Oreochromis
      niloticus) depends on rearing density.
AB  - BACKGROUND: Captive animal populations, be it for food production or conservation
      programmes, are often maintained at densities far beyond those in natural
      environments, which can have profound effects on behaviour, immune and stress
      levels, and ultimately welfare. How such alterations impact transcriptional
      responses to pathogen infection is a 'different kettle of fish' and remains
      poorly understood. Here, we assessed survival and gene expression profiles of
      infected fish reared at two different densities to elucidate potential functional
      genomic mechanisms for density-related differences in disease susceptibility.
      RESULTS: Utilising a whole-transcriptome sequencing (RNAseq) approach, we
      demonstrate that rearing density in tilapia (Oreochromis niloticus) significantly
      impacts susceptibility to the oomycete Saprolegnia parasitica, via altered
      transcriptional infection responses. Tilapia held at low densities have increased
      expression of genes related to stress, likely due to increased aggressive
      interactions. When challenged with Saprolegnia, low-density fish exhibit altered
      expression of inflammatory gene responses and enhanced levels of adaptive immune
      gene suppression compared to fish reared at higher density, resulting in
      significantly increased mortality rates. In addition, Saprolegnia infection
      substantially perturbs expression of circadian clock genes, with fish reared at
      low-density having higher levels of molecular clock dysregulation. CONCLUSIONS:
      Our results reveal the wide-scale impact of stocking density on transcriptional
      responses to infection and highlight the need to incorporate circadian biology
      into our understanding of disease dynamics in managed animals.

PMID- 30285629
TI  - Derivation of the economic value of R0 for macroparasitic diseases and
      application to sea lice in salmon.
AB  - BACKGROUND: Macroparasites, such as ticks, lice, and helminths, are a concern in
      livestock and aquaculture production, and can be controlled by genetic
      improvement of the host population. Genetic improvement should aim at reducing
      the rate at which parasites spread across the farmed population. This rate is
      determined by the basic reproduction ratio, i.e. [Formula: see text], which is
      the appropriate breeding goal trait. This study aims at providing a method to
      derive the economic value of [Formula: see text]. METHODS: Costs of a disease are
      the sum of production losses and expenditures on disease control. Genetic
      improvement of [Formula: see text] lowers the loss-expenditure frontier. Its
      economic effect depends on whether the management strategy is optimized or not.
      The economic value may be derived either from the reduction in losses with
      constant expenditures or from the reduction in expenditures with constant losses.
      RESULTS: When [Formula: see text] <= 1, the economic value of a further reduction
      is zero because there is no risk of a major epidemic. When [Formula: see text] >
      1 and management is optimized, the economic value increases with decreasing
      values of [Formula: see text], because both the mean number of parasites per host
      and frequency of treatments decrease at an increasing rate when [Formula: see
      text] decreases. When [Formula: see text] > 1 and management is not optimized,
      the economic value depends on whether genetic improvement is used for reducing
      expenditures or losses. For sea lice in salmon, the economic value depends on a
      reduction in expenditures with constant losses, and is estimated to be
      0.065?/unit [Formula: see text]/kg production. DISCUSSION: Response to selection
      for measures of disease prevalence cannot be predicted from quantitative genetic
      theory alone. Moreover, many studies fail to address the issue of whether genetic
      improvement results in reduced losses or expenditures. Using [Formula: see text]
      as the breeding goal trait, weighed by its appropriate economic value, avoids
      these issues. CONCLUSION: When management is optimized, the economic value
      increases with decreasing values of [Formula: see text] (until the threshold of
      [Formula: see text], where it drops to zero). When management is not optimized,
      the economic value depends on whether genetic improvement is used for reduced
      expenditures or production losses. For sea lice in salmon, the economic value is
      estimated to be 0.065 ?/unit [Formula: see text]/kg production.

PMID- 30285630
TI  - Biotite: a unifying open source computational biology framework in Python.
AB  - BACKGROUND: As molecular biology is creating an increasing amount of sequence and
      structure data, the multitude of software to analyze this data is also rising.
      Most of the programs are made for a specific task, hence the user often needs to
      combine multiple programs in order to reach a goal. This can make the data
      processing unhandy, inflexible and even inefficient due to an overhead of
      read/write operations. Therefore, it is crucial to have a comprehensive,
      accessible and efficient computational biology framework in a scripting language
      to overcome these limitations. RESULTS: We have developed the Python package
      Biotite: a general computational biology framework, that represents sequence and
      structure data based on NumPyndarrays. Furthermore the package contains seamless
      interfaces to biological databases and external software. The source code is
      freely accessible at https://github.com/biotite-dev/biotite . CONCLUSIONS:
      Biotite is unifying in two ways: At first it bundles popular tasks in sequence
      analysis and structural bioinformatics in a consistently structured package.
      Secondly it adresses two groups of users: novice programmers get an easy access
      to Biotite due to its simplicity and the comprehensive documentation. On the
      other hand, advanced users can profit from its high performance and
      extensibility. They can implement their algorithms upon Biotite, so they can skip
      writing code for general functionality (like file parsers) and can focus on what
      their software makes unique.

PMID- 30285631
TI  - Assessment of shared alleles in drought-associated candidate genes among southern
      California white oak species (Quercus sect. Quercus).
AB  - BACKGROUND: Hybridization and introgression are common phenomena among oak
      species. These processes can be beneficial by introducing favorable genetic
      variants across species (adaptive introgression). Given that drought is an
      important stress, impacting physiological and morphological variation and
      limiting distributions, our goal was to identify drought-related genes that might
      exhibit patterns of introgression influenced by natural selection. Using RNAseq,
      we sequenced whole transcriptomes of 24 individuals from three oaks in southern
      California: (Quercus engelmannii, Quercus berberidifolia, Quercus cornelius
      mulleri) and identified genetic variants to estimate admixture rates of all
      variants and those in drought genes. RESULTS: We found 398,042 variants across
      all loci and 4352 variants in 139 drought candidate genes. STRUCTURE analysis of
      all variants revealed the majority of our samples were assignable to a single
      species, but with several highly admixed individuals. When using drought
      associated variants, the same individuals exhibited less admixture and their
      allele frequencies were more polarized between Engelmann and scrub oaks than when
      using the total gene set. These findings are consistent with the hypothesis that
      selection may act differently on functional genes, such as drought-associated
      genes, and point to candidate genes that are suggestive of divergent selection
      among species maintaining adaptive differences. For example, the drought genes
      that showed the strongest bias against engelmannii-fixed oak variants in scrub
      oaks were related to sugar transporter, coumarate-coA ligases, glutathione S
      conjugation, and stress response. CONCLUSION: This pilot study illustrates that
      whole transcriptomes of individuals will provide useful data for identifying
      functional genes that contribute to adaptive divergence among hybridizing
      species.

PMID- 30285632
TI  - A high risk of sleep apnea is associated with less postoperative cognitive
      dysfunction after intravenous anesthesia: results of an observational pilot
      study.
AB  - BACKGROUND: The obstructive sleep apnea syndrome (OSAS) is characterized by
      temporary cerebral hypoxia which can cause cognitive dysfunction. On the other
      hand, hypoxia induced neurocognitive deficits are detectable after general
      anesthesia. The objective of this study was to evaluate the impact of a high risk
      of OSAS on the postoperative cognitive dysfunction after intravenous anesthesia.
      METHODS: In this single center trial between June 2012 and June 2013 43 patients
      aged 55 to 80 years with an estimated hospital stay of at least 3 days undergoing
      surgery were enrolled. Patients were screened for a high risk of OSAS using the
      STOP-BANG test. The cognitive function was assessed using a neuropsychological
      test battery, including the DemTect test for cognitive impairment and the RMBT
      test for memory, the day before surgery and within 36 h after extubation.
      RESULTS: Twenty-two of the 43 analyzed patients were identified as patients with
      a high risk of OSAS. Preoperatively, OSAS patients showed a significant worse
      performance only for the DemTect (p = 0.0043). However, when comparing pre- and
      postoperative test results, the OSAS patients did not show a significant loss in
      any test but significantly improved in RMBT test, whereas the control group
      showed a significant worse performance in three of eight tests. In five tests, we
      found a significant difference between the two groups with respect to the change
      from pre- to postoperative cognitive function. CONCLUSION: Patients with a high
      risk of OSAS showed a less impairment of memory function and work memory
      performance after intravenous anesthesia. This might be explained by a beneficial
      effect of intrinsic hypoxic preconditioning in these patients.

PMID- 30285633
TI  - Modeling tuberculosis dynamics with the presence of hyper-susceptible individuals
      for Ho Chi Minh City from 1996 to 2015.
AB  - BACKGROUND: The depletion of CD4 cell is the underlying reason for TB hyper
      susceptibility among people with HIV. Consequently, the trend of TB dynamics is
      usually hidden by the HIV outbreak. METHODS: Here, we aim to evaluate the trend
      of TB dynamics quantitatively by a simple mathematical model using the known
      prevalence of hyper-susceptible individuals in the population. In order to
      estimate the parameters governing transmission we fit this model in a maximum
      likelihood framework to both reported TB cases and data from samples tested with
      Interferon Gamma Assay from Ho Chi Minh City - a city with high TB transmission
      and strong synchronization between HIV/AIDS and TB dynamics. RESULTS: Our results
      show that TB transmission in HCMC has been declining among people without HIV; we
      estimate a 18% (95% CI: 9-25%) decline in the transmission parameter between 1996
      and 2015. Furthermore, we show that co-infected patients have limited
      contribution to the transmission process. For hyper-susceptible individuals, our
      model suggests that the risk of a new active TB infection occurring is
      significantly higher than the risk of relapsed active TB, while this is not the
      case for people without hyper-susceptibility. CONCLUSIONS: The increase of TB
      notifications in Ho Chi Minh City from 1996 to 2008 is evitable when, as
      occurred, the number of hyper-susceptible individuals increased faster than the
      decrease of TB transmission rate. The sharp decrease in TB notifications observed
      in this city from 2008 to 2015 is the combined result of the decrease of TB
      transmission rate and the decrease of hyper-susceptible individuals in the
      population. For hyper-susceptible individuals, we propose that the reason for the
      reduced relapsed active TB risk is HIV treatment delay. According to HIV
      treatment guidelines issued by Vietnam's Ministry of Health, hyper-susceptible
      individuals usually have to wait until their CD4 cell count falls under 350
      cells/MUl to start ART. Once patients begin ART, they will remain on ART for the
      rest of their life and thus have greater protection against relapses of TB. We
      therefore hypothesize that the delay in using ART imposes considerable TB burden
      on HCMC despite the declining transmission process.

PMID- 30285634
TI  - Double trouble: visceral leishmaniasis in twins after traveling to Tuscany - a
      case report.
AB  - BACKGROUND: Leishmaniasis is endemic in many countries worldwide, with a
      prevalence of 12 million people infected, and an estimated annual incidence of
      500 000 visceral leishmaniasis cases. In Europe visceral leishmaniasis is
      considered endemic mainly in the Mediterranean countries and cases in non-endemic
      European countries north of the Alps have primarily been reported in returning
      travellers. The incubation period is typically described between 6 weeks to 6
      months. The cases presented highlight the occurrence of longer incubation periods
      and illustrate the individual variability for progression from infection to
      disease. CASE PRESENTATION: We report the cases of 18-months-old twin girls
      living at the German-Swiss border, who developed visceral leishmaniasis 7 and 15
      months after travelling to Tuscany. They presented with fever of unknown origin
      and pancytopenia. Both had splenomegaly and in the first case haemophagocytic
      lymphohistiocytosis or leukaemia was initially included in the differential
      diagnosis. Diagnosis of visceral leishmaniasis was confirmed by presence of
      intracytoplasmic localised leishmania parasites on bone marrow aspirate and/or
      positive leishmania serology. Both girls responded well to treatment with
      liposomal amphotericin B. The mother and two older siblings remained uninfected,
      while the father was diagnosed to be an asymptomatic carrier. CONCLUSION:
      Visceral leishmaniasis is an important differential diagnosis for fever of
      unknown origin and pancytopenia in young children living in countries with
      endemic disease and highlights the importance of obtaining a detailed travel
      history. Hemophagocytic lymphohistiocytosis and acute leukaemia present with
      similar symptoms and consequently are important differential diagnoses. Factors
      determining progression from infection to disease are not fully understood but
      younger age seems to be an important risk factor. Screening of siblings from
      affected individuals therefore may be warranted.

PMID- 30285636
TI  - Comparing survival functions with interval-censored data in the presence of an
      intermediate clinical event.
AB  - BACKGROUND: In the presence of an intermediate clinical event, the analysis of
      time-to-event survival data by conventional approaches, such as the log-rank
      test, can result in biased results due to the length-biased characteristics.
      METHODS: In the present study, we extend the studies of Finkelstein and Nam &
      Zelen to propose new methods for handling interval-censored data with an
      intermediate clinical event using multiple imputation. The proposed methods
      consider two types of weights in multiple imputation: 1) uniform weight and 2)
      the weighted weight methods. RESULTS: Extensive simulation studies were performed
      to compare the proposed tests with existing methods regarding type I error and
      power. Our simulation results demonstrate that for all scenarios, our proposed
      methods exhibit a superior performance compared with the stratified log-rank and
      the log-rank tests. Data from a randomized clinical study to test the efficacy of
      sorafenib/sunitinib vs. sunitinib/sorafenib to treat metastatic renal cell
      carcinoma were analyzed under the proposed methods to illustrate their
      performance on real data. CONCLUSIONS: In the absence of intensive iterations,
      our proposed methods show a superior performance compared with the stratified log
      rank and the log-rank test regarding type I error and power.

PMID- 30285635
TI  - Prevalence and genotypes of group A rotavirus among outpatient children under
      five years old with diarrhea in Beijing, China, 2011-2016.
AB  - BACKGROUND: Rotavirus is a leading cause of severe diarrheal disease, and one of
      the common causes of death in children aged under five years old. The dominant
      epidemic strains may change in different years in the same area. In order to
      provide evidence for rotavirus epidemic control and inform vaccine development,
      we analyzed epidemiological patterns and genetic characteristics of rotavirus in
      Beijing during 2011-2016. METHODS: Stool specimens of outpatient children under
      five years old were collected from three children's hospitals on a weekly basis.
      Group A rotavirus antigens were detected using enzyme-linked immunosorbent assay
      (ELISA) kit. The partial VP4 genes and VP7 genes of rotavirus were both amplified
      and sequenced. Genotyping and phylogenetic analyses were performed. Logistic
      regression and Chi-square tests were performed to determine differences across
      age groups, districts and years in rotavirus prevalence and genotype
      distribution. RESULTS: A total of 3668 stool specimens from children with acute
      diarrhea identified through hospital-based surveillance were collected from 2011
      to 2016 in Beijing. A total of 762 (20.8%) specimens tested positive for
      rotavirus. The rotavirus-positive rate was highest among the 1-2 years old age
      group (29.0%, 310/1070). November, December and January were the highest
      rotavirus-positive rate months each year. G9 was the most common G genotype
      (64.4%, 461/716), and P [8] was the most common P genotype (87.0%, 623/716) among
      the 716 rotavirus-positive specimens. G9P [8], G3P [8] and G2P [4] were the most
      common strains. The rotavirus-positive rates of samples in 2012 and 2013 were
      higher than that in 2011, and the dominant genotype changed from G3P [8] to G9P
      [8] in 2012 and 2013. VP7 gene sequences of G9 strains in this study clustered
      into two main lineages. Most of the G9 strains exhibited the highest nucleotide
      similarity (99.1%~ 100.0%) to the strain found in Japan (MI1128). VP4 gene
      sequences of P [8] strains were almost P[8]b. CONCLUSIONS: Rotavirus accounted
      for more than one fifth of childhood diarrhea in Beijing during the study period.
      Targeted measures such as immunization with effective rotavirus vaccines should
      be carried out to reduce the morbidity and mortality due to rotavirus.

PMID- 30285637
TI  - Long-term evaluation of the implementation of a large fall and fracture
      prevention program in long-term care facilities.
AB  - BACKGROUND: Falls and fractures are extremely frequent in long-term care
      facilities (LTCFs). Therefore, a fall and fracture prevention program was started
      in nearly 1000 LTCFs in Bavaria/Germany between 2007 and 2010. The components of
      the program were exercise classes, the documentation of falls, environmental
      adaptations, medication reviews, the recommendation to use hip protectors and
      education of staff. The present study aimed to provide a comprehensive evaluation
      of the implementation process of the program regarding results of the
      implementation phase and the follow-up of 3-9 years after start of
      implementation. METHODS: Data from numerous sources were used, including data
      from published studies, statistical data, health insurance claims data and
      unpublished data from an online questionnaire. To incorporate different aspects,
      time periods and results, the RE-AIM framework was applied. RESULTS: The program
      was adopted by 942 of the 1150 eligible LTCFs and reached about 62,000 residents.
      During the implementation phase exercise classes and recommendation about
      environmental adaptations were offered in nearly all LTCFs. 13.5% of the
      residents participated in exercise classes. Hip protectors were available for
      9.2% of all residents. In the first implementation wave, femoral fracture rate
      was significantly reduced by 18% in the first year. At follow-up nearly 90% of
      all LTCFs still offered exercise classes, which were attended by about 11% of
      residents. However, only 10% of the exercise classes completely fulfilled the
      requirements of an effective strength and balance training. Individual advice
      about environmental adaptations was provided in 74.3% of the LTCFs and nearly all
      LTCFs claimed to offer hip protectors to their residents. A long-term effect of
      the program on femoral fractures could not be detected. CONCLUSIONS: The program
      did not affect the femoral fracture rate in the long run. Possible reasons could
      be a high turn-over of the staff, a reduced fidelity of training components or a
      shift in daily priorities among the staff.

PMID- 30285638
TI  - A comparison of pyogenic liver abscess in patients with or without diabetes: a
      retrospective study of 246 cases.
AB  - BACKGROUND: Pyogenic liver abscess(PLA) has become common in patients with
      diabetes mellitus (DM), but it is unclear whether differences exist between
      patients with and without DM. A retrospective study was performed to identify
      these differences, summarize the clinical experience, and improve the diagnosis
      and treatment of PLA. METHODS: The patients were enrolled in a teaching hospital
      from January 2012 to December 2016. The patients were separated into two groups
      based on comorbidity with diabetes mellitus (DM). The DM group was further
      separated into two subgroups according to the HbA1C concentration to investigate
      whether glycaemic control affected the clinical characteristics of PLA patients
      with DM. Chi-square, Fisher's exact test, and t-tests were used to analyse and
      evaluate differences between the two groups. RESULTS: Two hundred and forty-six
      PLA patients were identified and 90 (36.6%) had comorbid DM. Patients with DM
      were older, had higher levels of alkaline phosphatase and gamma-glutamyl
      transferase, hypertension, a loss of body weight, a single abscess, and combined
      antibiotic therapy with the use of carbapenems and Klebsiella pneumoniae in their
      blood cultures but a less frequent history of abdominal surgery and Escherichia
      coli in their pus cultures. When DM patients were compared to non-DM patients,
      each of these differences was significant (P < 0.05). Diabetic PLA patients with
      poor glycaemic control had a significantly higher proportion of fever and both
      lobes abscess(P < 0.05). CONCLUSION: PLA patients with diabetes are older, have
      more serious complications, a higher prevalence of cardiovascular disease, an
      increased use of combined antibiotic therapy with carbapenem, and K. pneumoniae
      as the predominant pathogen, but these patients had fewer abdominal surgeries and
      fewer E. coli infections. In addition, poorly controlled glycaemia in diabetic
      PLA patients is associated with high incidence of fever and both lobes abscess.

PMID- 30285639
TI  - Identification of risk factors for pancreatic pseudocysts formation, intervention
      and recurrence: a 15-year retrospective analysis in a tertiary hospital in China.
AB  - BACKGROUND: Pancreatic pseudocyst (PPC) is a common complication of acute and
      chronic pancreatitis. To our knowledge no study has systematically reported the
      risk factors for the formation, intervention and recurrence of PPC. Therefore,
      the present study aimed to investigate the potential risk factors for PPC, with
      regards to its formation, intervention and recurrence. METHODS: A database
      containing 5106 pancreatitis patients was retrospectively analyzed. As a result,
      a total of 4379 eligible patients were identified and divided into 2 groups: PPC
      group (group A, n = 759) and non-PPC group (group B, n = 3620). The PPC group was
      subdivided into 2 groups: intervention PPC (group C, n = 347) and resolution PPC
      (group D, n = 412). The differences in surgical complication and recurrence rates
      were compared among 347 PPC patients receiving different interventions, including
      surgical, endoscopic and percutaneous drainages. Furthermore, group C was
      subdivided into 2 groups: recurrent PPC (group E, n = 34) and non-recurrent PPC
      (group F, n = 313). All possible risk factors for PPC formation, intervention and
      recurrence were determined by multivariate regression analysis. RESULTS: In this
      study, PPC was developed in 17.3% (759/4379) of pancreatitis patients. The
      significant risk factors for PPC formation included alcoholic pancreatitis (OR,
      6.332; 95% CI, 2.164-11.628; p = 0.031), chronic pancreatitis (CP) (OR, 5.822;
      95% CI, 1.921-10.723; p = 0.006) and infected pancreatic necrosis (OR, 4.253; 95%
      CI, 3.574-7.339; p = 0.021). Meanwhile, the significant risk factors of PPC
      patients who received intervention were alcoholic pancreatitis (OR, 7.634; 95%
      CI, 2.125-13.558; p = 0.016), size over 6 cm (OR, 8.834; 95% CI, 2.017-16.649; p
      = 0.002) and CP (OR, 4.782; 95% CI, 1.897-10.173; p = 0.038). In addition, the
      recurrence rate in PPC patients treated with percutaneous drainage was found to
      be the highest (16.3%) among the three intervention groups. Furthermore,
      percutaneous drainage was the only risk factor of PPC recurrence (OR, 7.812; 95%
      CI, 3.109-23.072; p = 0.013) identified from this retrospective cohort study.
      CONCLUSIONS: Alcoholic pancreatitis and CP are the main risk factors for PPC
      formation and intervention, but not PPC recurrence. A higher recurrence rate is
      found in PPC patients treated with percutaneous drainage, as compared to
      endoscopic and surgical interventions.

PMID- 30285640
TI  - Relationship of ideal cardiovascular health metrics with retinal vessel calibers
      and retinal nerve fiber layer thickness: a cross-sectional study.
AB  - BACKGROUND: Ideal cardiovascular health (CVH) metrics have been found to be
      associated with subclinical vascular abnormalities. However, the relationship
      between ideal CVH metrics and retinal vessel calibers and retinal nerve fiber
      layer (RNFL) thickness in a Chinese population is unknown. METHODS: We collected
      information on the seven ideal CVH metrics among 3376 participants aged 40 years
      or older from the Asymptomatic Polyvascular Abnormalities Community Study in
      2012. Retinal vessel calibers and RNFL thickness were assessed by retinal
      photography and spectral-domain optical coherence tomography. Multivariable
      linear models were used to analyze the relationship between ideal CVH metrics and
      retinal parameters. RESULTS: With the decreased number of ideal CVH metrics,
      central retinal arteriolar equivalents (CRAE) was significantly narrowed and
      arterio- venous ratio (AVR) significantly decreased (p < 0.0001). While the RNFL
      thickness and central retinal venous equivalents (CRVE) showed no significant
      changes with the decreased ideal CVH metrics. Linear regression showed that both
      CRAE and AVR was positively related with the number of ideal CVH metrics
      (regression coefficient beta: 0.806, 95% confidence interval (CI): 0.266-1.346
      for CRAE (micron); and regression coefficient beta: 0.005, 95% CI: 0.002-0.009
      for AVR) after adjusting for age (year), sex = male (n), education (n), average
      monthly income (Y) and other related risk factors. CONCLUSIONS: These findings
      suggested a clear positive relationship between the number of ideal CVH metrics
      and CRAE and AVR in Chinese population, supporting the importance of ideal health
      behaviors and factors in subclinical vascular abnormalities prevention.

PMID- 30285641
TI  - Identifying and understanding the health and social care needs of older adults
      with multiple chronic conditions and their caregivers: a scoping review.
AB  - BACKGROUND: As the population is aging, the number of persons living with
      multiple chronic conditions (MCC) is expected to increase. This review seeks to
      answer two research questions from the perspectives of older adults with MCC,
      their caregivers and their health care providers (HCPs): 1) What are the health
      and social care needs of community-dwelling older adults with MCC and their
      caregivers? and 2) How do social and structural determinants of health impact
      these health and social care needs? METHODS: We conducted a scoping review guided
      by a refinement of the Arksey & O'Malley framework. Articles were included if
      participants were 55 years or older and have at least two chronic conditions. We
      searched 7 electronic databases. The data were summarized using thematic
      analysis. RESULTS: Thirty-six studies were included in this review: 28 studies
      included participants with MCC; 12 studies included HCPs; 5 studies included
      caregivers. The quality of the studies ranged from moderate to good. Five main
      areas of needs were identified: need for information; coordination of services
      and supports; preventive, maintenance and restorative strategies; training for
      older adults, caregivers and HCPs to help manage the older adults' complex
      conditions; and the need for person-centred approaches. Structural and social
      determinants of health such as socioeconomic status, education and access
      influenced the needs of older adults with MCC. CONCLUSION: The review highlights
      that most of the needs of older adults with MCC focus on lack of access to
      information and coordination of care. The main structural and social determinants
      that influenced older adults' needs were their level of education/health literacy
      and their socioeconomic status.

PMID- 30285642
TI  - Using an introduced index to assess the association between food diversity and
      metabolic syndrome and its components in Chinese adults.
AB  - BACKGROUND: It is reported that an increase in food diversity would lower the
      risk of cardiac-cerebral vascular diseases. METHODS: A new index was introduced
      to develop a Chinese healthy food diversity (HFD) index, exploring the
      association with metabolic syndrome (MetS) and its components among Chinese
      adults. Two sets of data were used. The primary data were from a cross-sectional
      survey conducted in 2016 called the Chinese Urban Adults Diet and Health Study
      (CUADHS); the verification data were from the China Health and Nutrition Survey
      (CHNS) of 2009. The Chinese HFD index was developed according to the Chinese
      Dietary Guideline, with food consumption information from 24-h dietary recalls.
      The association between the index and MetS and its components was explored in
      logistic regression models. RESULTS: Among 1520 participants in the CUADHS, the
      crude prevalence of MetS was 36.4%, which was 29.0% after the standardisation of
      age and gender by the 2010 Chinese national census. In the CUADHS, the HFD index
      ranged from 0.04 to 0.63. The value of the index among participants who are male,
      young, poorly educated, drinking or smoking, and with high energy intakes was
      significantly lower than that of their counterparts. In the verification dataset
      of the CHNS, there were 2398 participants, and the distribution of different
      genders and age groups was more balanced. The crude prevalence of MetS in the
      CHNS was 27.3% and the standardised prevalence was 19.5%. The Chinese HFD index
      ranged from 0.02 to 0.62. In the CUADHS, the Chinese HFD index was not
      significantly associated with MetS in covariate-adjusted models or with its
      components. In the CHNS, the Chinese HFD index had a significantly negative
      correlation with MetS and its components (i.e., elevated fasting glucose and
      elevated waist circumference) in covariate-adjusted models. CONCLUSIONS:
      Increased food diversity may decrease the risk of MetS, which is important in
      dietary interventions of cardiac-cerebral vascular disease. This underscores the
      necessity of continued investigation into the role of HFD in the prevention of
      MetS and provides an integral framework for ongoing research.

PMID- 30285643
TI  - A descriptive analysis of non-Cochrane child-relevant systematic reviews
      published in 2014.
AB  - BACKGROUND: Consumers, clinicians, policymakers and researchers require high
      quality evidence to guide decision-making in child health. Though Cochrane
      systematic reviews (SRs) are a well-established source of evidence, little is
      known about the characteristics of non-Cochrane child-relevant SRs. To complement
      published descriptions of Cochrane SRs, we aimed to characterize the
      epidemiologic, methodological, and reporting qualities of non-Cochrane child
      relevant SRs published in 2014. METHODS: English-language child-relevant SRs of
      quantitative primary research published outside the Cochrane Library in 2014 were
      eligible for this descriptive analysis. A research librarian searched MEDLINE,
      CINAHL, Web of Science, and PubMed in August 2015. A single reviewer screened
      articles for inclusion; a second verified the excluded studies. Reviewers
      extracted: general characteristics of the review; included study characteristics;
      methodological approaches. We performed univariate analyses and presented the
      findings narratively. RESULTS: We identified 1598 child-relevant SRs containing a
      median (IQR) 19 (11, 33) studies. These originated primarily from high-income
      countries (n = 1247, 78.0%) and spanned 47 of the 53 Cochrane Review Groups. Most
      synthesized therapeutic (n = 753, 47.1%) or epidemiologic (n = 701, 43.8%)
      evidence. Though 39.3% (n = 628) of SRs included evidence related to children
      only, few were published in pediatric-specific journals (n = 283, 17.7%).
      Reporting quality seemed poor based on the items we assessed; few reviews
      mentioned an a-priori protocol (n = 246, 15.4%) or registration (n = 111, 6.9%),
      and only 23.4% (n = 374) specified a primary outcome. Many SRs relied solely on
      evidence from non-RCTs (n = 796, 49.8%). Less than two-thirds (n = 953, 59.6%)
      appraised the quality of included studies and assessments of the certainty of the
      body of evidence were rare (n = 102, 6.4%). CONCLUSIONS: Child-relevant Cochrane
      SRs are a known source of high quality evidence in pediatrics. There exists,
      however, an abundance of evidence from non-Cochrane SRs that may be
      complementary. Our findings show that high-quality non-Cochrane SRs may not be
      practical nor easy for knowledge users to find. Improvements are needed to ensure
      that evidence syntheses published outside of the Cochrane Library adhere to the
      high standard of conduct and reporting characteristic of Cochrane SRs.

PMID- 30285644
TI  - The value of shock index in prediction of cardiogenic shock developed during
      primary percutaneous coronary intervention.
AB  - BACKGROUND: Shock index(SI) is a conventional predictive marker for haemodynamic
      state. Its breakpoint varies by different conditions according to previous
      studies. The current study was performed to evaluate the capability of SI in
      prediction of cardiogenic shock(CS) developed during primary percutaneous
      coronary intervention (pPCI). METHODS: Total 870 patients of ST segment elevation
      myocardial infarction(STEMI) who were haemodynamic stable before pPCI were
      involved in the study. In this cohort, 625 consecutive patients composed analysis
      series and 245 consecutive patients composed validation series. Multivariate
      regression analysis was used to evaluate whether SI was a significant predictor
      of developed CS and Hosmer-Lemeshow test was used to assess the goodness of model
      fitness. Receiver-operating characteristics (ROC) analysis was used to compare
      the predictive capability of SI with other predictors. The sensitivity,
      specificity, accuracy, positive and negative predictive values of SI at different
      cutoff values was compared to identify a best breakpoint. RESULTS: In the
      analysis series, SI and Killips classification were identified as independent
      predictors. ROC analysis demonstrated the diagnostic capability of SI was
      superior to pre-procedural systolic blood pressure(SBP) or heart rate(HR) alone
      (0.8113 vs 0.7582, P = 0.04 and 0.8113 vs 0.7111, P < 0.001). The diagnostic
      capability of SI was equivalent to that of combination of SBP, HR and Killips
      claasification(0.8133 vs 0.8137, P = 0.97). SI had a high specificity and low
      sensitivity. When the cutoff value was set at 0.93, the positive predictive
      value, negative predictive value and diagnostic accuracy was 42.6%, 95.1% and
      87.4% respectively. In validation series, the area under ROC curve was 0.8245,
      which was similar to that in the analysis series. The positive predictive value,
      negative predictive value and diagnostic accuracy at the cutoff value of 0.93 was
      53.8%, 93.2% and 88.9% respectively. CONCLUSIONS: SI has a high predictive
      accuracy for developing CS during pPCI in STEMI patients. It is an excellent
      exclusion diagnosis index rather than confirmative diagnosis index.

PMID- 30285645
TI  - Effects of 12-month home-based physiotherapy on duration of living at home and
      functional capacity among older persons with signs of frailty or with a recent
      hip fracture - protocol of a randomized controlled trial (HIPFRA study).
AB  - BACKGROUND: Health concerns, such as frailty and osteoporotic fractures decrease
      functional capacity and increase use of health and social care services in the
      aging population. The ability to continue living at home is dependent on
      functional capacity, which can be enhanced by rehabilitation. We study the
      effects of a 12-month home-based physiotherapy program with 12-month follow-up on
      duration of living at home, functional capacity, and the use of social and health
      care services among older persons with signs of frailty, or with a recently
      operated hip fracture. METHODS: This is a non-blinded, parallel group, randomized
      controlled trial performed in South Karelia Social and Health Care District,
      Finland (population 131,000). Three hundred community-dwelling older persons with
      signs of frailty (age >= 65) and 300 persons with a recent hip fracture (age >=
      60) will be recruited. Frailty is screened by FRAIL questionnaire and verified by
      modified Fried's frailty criteria. Both patient groups will be randomized
      separately to a physiotherapy and a usual care arm. Individualized, structured
      and progressive physiotherapy will be carried out for 60 min, twice a week for 12
      months at the participant's home. The primary outcome at 24 months is duration of
      living at home. Our hypothesis is that persons assigned to the physiotherapy arm
      will live at home for six months longer than those in the usual care arm.
      Secondary outcomes are functional capacity, frailty status, health-related
      quality-of-life, falls, use and costs of social and health care services, and
      mortality. Assessments, among others Short Physical Performance Battery,
      Functional Independence Measure, Mini Nutritional Assessment, and Mini-Mental
      State Examination will be performed at the participant's home at baseline, 3, 6,
      and 12 months. Register data on the use and costs of social and health care
      services, and mortality will be monitored for 24 months. DISCUSSION: Our trial
      will provide new knowledge on the potential of intensive, long-term home-based
      physiotherapy among older persons at risk for disabilities, to enhance functional
      capacity and thereby to postpone the need for institutional care, and diminish
      the use of social and health care services. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT02305433 , Registered Nov 28, 2014.

PMID- 30285646
TI  - Deep learning based low-cost high-accuracy diagnostic framework for dementia
      using comprehensive neuropsychological assessment profiles.
AB  - BACKGROUND: The conventional scores of the neuropsychological batteries are not
      fully optimized for diagnosing dementia despite their variety and abundance of
      information. To achieve low-cost high-accuracy diagnose performance for dementia
      using a neuropsychological battery, a novel framework is proposed using the
      response profiles of 2666 cognitively normal elderly individuals and 435 dementia
      patients who have participated in the Korean Longitudinal Study on Cognitive
      Aging and Dementia (KLOSCAD). METHODS: The key idea of the proposed framework is
      to propose a cost-effective and precise two-stage classification procedure that
      employed Mini Mental Status Examination (MMSE) as a screening test and the
      KLOSCAD Neuropsychological Assessment Battery as a diagnostic test using deep
      learning. In addition, an evaluation procedure of redundant variables is
      introduced to prevent performance degradation. A missing data imputation method
      is also presented to increase the robustness by recovering information loss. The
      proposed deep neural networks (DNNs) architecture for the classification is
      validated through rigorous evaluation in comparison with various classifiers.
      RESULTS: The k-nearest-neighbor imputation has been induced according to the
      proposed framework, and the proposed DNNs for two stage classification show the
      best accuracy compared to the other classifiers. Also, 49 redundant variables
      were removed, which improved diagnostic performance and suggested the potential
      of simplifying the assessment. Using this two-stage framework, we could get 8.06%
      higher diagnostic accuracy of dementia than MMSE alone and 64.13% less cost than
      KLOSCAD-N alone. CONCLUSION: The proposed framework could be applied to general
      dementia early detection programs to improve robustness, preciseness, and cost
      effectiveness.

PMID- 30285647
TI  - Epidemiology of Paediatric constipation in Indonesia and its association with
      exposure to stressful life events.
AB  - BACKGROUND: We aimed to study the epidemiology and risk factors, including
      exposure to emotional stress, for constipation in Indonesian children and
      adolescents of 10-17 year age group. METHODS: A cross-sectional survey using a
      validated, self-administered questionnaire was conducted in randomly selected
      children and adolescents in nine state junior high schools from five districts of
      Jakarta. All of them were from urban areas. Constipation was defined as a
      diagnosis by using the Rome III criteria. RESULTS: Of 1796 children included in
      the analysis, 328 (18.3%; 95% CI 016-0.2) had constipation. Females and those
      residing in North Jakarta showed risks associated with constipation in school-age
      children and adolescents. Symptoms independently associated with constipation
      were abdominal pain (64% vs 43.3% of control) and straining (22.9% vs 6.3%). The
      prevalence of constipation was significantly higher in those with stressful life
      events such as father's alcoholism (adjusted OR 1.91, 95% CI 1.27-2.89, P =
      0.002), severe illness of a close family member (adjusted OR 1.77, 95% CI 1.12
      2.80, P = 0.014), hospitalization of the child for another illness (adjusted OR
      1.68, 95% CI 1.22-2.31, P < 0.001), being bullied at school (adjusted OR 1.67,
      95% CI 1.01-2.76, P = 0.047) and loss of a parent's job (adjusted OR 1.39, 95% CI
      1.03-1.88, P = 0.034). CONCLUSIONS: Constipation in children and adolescent is a
      significant health problem, affecting almost 20% of Indonesian school-age
      children and adolescents. Common school and home related stressful life events
      appear to have predisposed these children to develop constipation.

PMID- 30285648
TI  - Identity and validity of conserved B cell epitopes of filovirus glycoprotein:
      towards rapid diagnostic testing for Ebola and possibly Marburg virus disease.
AB  - BACKGROUND: Ebolavirus and Marburgvirus are genera of the virus family
      Filoviridae. Filoviruses cause rare but fatal viral hemorrhagic fevers (VHFs) in
      remote villages of equatorial Africa with potential for regional and
      international spread. Point-of-care (POC) rapid diagnostic tests (RDTs) are
      critical for early epidemic detection, reponse and control. There are 2 RDTs for
      Zaire ebolavirus (EBOV), but not other Ebolavirus spp. or Marburg marburgvirus
      (MARV). We validate 3 conserved B cell epitopes of filovirus glycoprotein (GP)
      using ebola virus diseases (EVD) survivor samples, towards devising pan-filovirus
      RDTs. METHODS: In-silico Immuno-informatics:- (a) multiple and basic local
      alignments of amino-acid sequences of filovirus (4 Ebolavirus spp. & MARV) Gp1, 2
      and epitope prediction and conservation analyses within context of ClusterW,
      BLAST-P and the immune epitope database analysis resource (IEDB-AR); alongside
      (b) in-vitro enzyme immuno-assays (EIAs) for SUDV Gp1, 2 antigen and host
      specific antibodies (IgM and IgG) among 94 gamma irradiated EVD survivor serum
      and 9 negative controls. RESULTS: Linear B cell epitopes were present across the
      entire length of all Gp1, 2, most lying in the region between amino acids
      positioned 350 and 500. Three seperate epitopes 97/80_GAFFLYDRLAST,
      39_YEAGEWAENCY and 500_CGLRQLANETTQALQLFLRATTELR (designated UG-Filo-Peptide- 1,
      2 and 3 respectively) were conserved within all studied filovirus species Gp1, 2.
      Gp1, 2 host specific IgM levels were comparably low (av. ODs < 0.04 [95% CI:
      0.02837 to 0.04033]) among the 9 negative controls and 57 survivor samples
      analyzed. Host specific IgG levels, on the other hand, were elevated (av. ODs >
      1.7525 [95% CI: 0.3010 to 3.1352]) among the 92 survivor samples relative to the
      9 negative controls (av. ODs < 0.2.321 [95% CI: -0.7596 to 0.5372]). Filovirus
      Gp1, 2 antigen was not detected [av. ODs < 0.20] within EVD survivor serum
      relative to recombinant protein positive controls [av. ODs = 0.50]. CONCLUSIONS:
      These conserved B cell epitopes of filovirus Gp1, 2 and their derivative
      antibodies are promising for research and development of RDTs for EVD, with
      potential for extension to detect MVD.

PMID- 30285649
TI  - Biochemical and molecular characterization of adult patients with type I Gaucher
      disease and carrier frequency analysis of Leu444Pro - a common Gaucher disease
      mutation in India.
AB  - BACKGROUND: Gaucher disease is a rare pan-ethnic disorder which occurs due to an
      increased accumulation of undegraded glycolipid glucocerebroside inside the
      cells' lysosomes. A beta-Glucosidase (GBA) gene defect results in
      glucocerebrosidase enzyme deficiency. Though the disease is mainly diagnosed in
      childhood, the adult manifestation is often missed or identified late due to the
      failure to recognize the heterogeneous clinical presentation. The present study
      includes seven unrelated Indian adult patients (age range: 20-40 years) having
      splenomegaly, with or without hepatomegaly, cytopenia and bone abnormality.
      METHODS: The biochemical investigation implicated measuring plasma
      chitotriosidase enzyme activity followed by confirmatory test of beta-Glucosidase
      enzyme activity from the leukocytes. The molecular characterization involved
      patients' initial screening for the common Gaucher mutation (Leu444Pro). Later,
      all patients were subjected to whole GBA gene coding region study using
      bidirectional Sanger sequencing. The population screening for common Gaucher
      disease mutation (Leu444Pro) was executed in 1200 unrelated and healthy Indian
      subjects by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction
      technique. The allele frequency was calculated using Hardy-Weinberg formula.
      RESULTS: The biochemical analysis revealed a significant reduction in the beta
      Glucosidase activity in all the patients. Also, an elevated level of plasma
      Chitotriosidase activity in five patients supported their diagnosis of Gaucher
      disease. Sanger sequencing established four patients with homozygous variation
      and three patients with compound heterozygous variation in GBA gene. This study
      uncovers two missense variants (Ala448Thr and Val17Gly) not previously reported
      in Gaucher disease patients. Also the known mutations like Leu444Pro, Arg329Cys,
      Asp315Asn, Ser125Arg, and Arg395Cys were identified in these patients. The
      homology modeling suggested the destabilization of the protein structure due to
      novel variants. The Leu444Pro mutation screening in the Indian population spotted
      two people as a carrier. This emerged the carrier frequency of 1:600 along with
      wild-type allele frequency 0.97113 and mutant allele frequency 0.02887.
      CONCLUSIONS: The study reports novel and known variants identified in the GBA
      gene in seven adult patients. The given study is the first report on the carrier
      frequency of the Leu444Pro mutant allele in an Indian population which will help
      understanding the burden and susceptibility of Gaucher disease to affect next
      generation in India.

PMID- 30285650
TI  - Emergency response time and pre-hospital trauma survival rate of the national
      ambulance service, Greater Accra (January - December 2014).
AB  - BACKGROUND: Every year, about 1.2 million people die through road traffic crashes
      worldwide. Majority of these deaths occur in Africa where most of their emergency
      medical services are underdeveloped. In 2004, Ghana established the National
      Ambulance Council to provide timely and efficient pre-hospital emergency medical
      care to the sick and injured. Pre-hospital emergency medical service is essential
      for accident victims since it has the potential of saving lives. The study sought
      to determine the relationship between pre-hospital trauma survival rate and
      response time to emergencies and factors associated to pre-hospital trauma
      survival  in Accra, Ghana. METHODS: The study was a cross sectional study which
      reviewed pre-hospital care forms of trauma patients from the fourteen ambulance
      stations in the Greater Accra region from January to December 2014. Data were
      extracted from these forms and the response time estimated. Conscious patients
      who were alert were categorized as responsive under the AVPU scale. The
      proportion of patients who survived pre-hospital trauma and  the time pre
      hospital trauma cases were responded to was estimated. Multiple logistic
      regression analysis was conducted to determine which variables were associated
      with survival. RESULTS: A total of 652 pre-hospital care forms were reviewed.
      About 87% survived pre-hospital trauma. The average response time to patients was
      (16.9 +/- 0.7) minutes and the median transportation time of the patient was 82
      min. Level of consciousness of a patient and response time of patients
      transported was found to be significantly associated with pre-hospital trauma
      survival. CONCLUSION: There was a high trauma patient survival rate among victims
      attended to by an NAS. The average response time in Greater Accra region in the
      14 ambulance stations is 16.9 min which is not different from the 17 min recorded
      in 2013 by NAS. Factors that were associated with pre-hospital survival were
      alertness in the level of consciousness and response time less than 17 min.

PMID- 30285651
TI  - Hepatic expression of Yin Yang 1 (YY1) is associated with the non-alcoholic fatty
      liver disease (NAFLD) progression in patients undergoing bariatric surgery.
AB  - BACKGROUND: This study is to investigate the association between the hepatic
      expression of Yin Yang 1 (YY1) and the progression of non-alcoholic fatty liver
      disease (NAFLD) in patients undergoing bariatric surgery. METHODS: Obese patients
      undergoing bariatric surgery were included. Liver tissues were subjected to the
      quantitative real-time PCR, Western blot analysis, and immunohistochemical assay,
      to determine the expression levels of YY1. RESULTS: Totally 88 patients were
      included. According to the NAFLD activity score (NAS), these patients were
      divided into the control (n = 12), steatosis (n = 20), non-defining NASH (n =
      38), and NASH (n = 18) groups. Significant differences in the serum glucose,
      insulin, ALT, AST, and HOMA-IR levels were observed among these different NAFLD
      groups. Hepatic YY1 expression had correlation with serum glucose, insulin, HOMA
      IR, ALT, AST, triglycerides, HDL, and GGT. Immunohistochemical analysis showed
      that, compared with the control group, the expression levels of YY1 were
      significantly higher in the non-defining NASH and NASH groups. In addition,
      multivariate regression model showed that the serum ALT and YY1 levels were
      strongly associated with the NAFLD activity. CONCLUSIONS: Several factors are
      associated with NAFLD progression, including the expression of YY1. Our findings
      contribute to understanding of the pathogenesis of NAFLD. TRIAL REGISTRATION:
      NCT03296605 , registered on September 28, 2017.

PMID- 30285652
TI  - Quantifying the effects of aging and urbanization on major gastrointestinal
      diseases to guide preventative strategies.
AB  - BACKGROUND: This study aimed to quantify the effects of aging and urbanization on
      major gastrointestinal disease (liver cirrhosis, hepatitis B, diarrhea, liver
      cancer, stomach cancer, pancreas cancer, hepatitis C, esophagus cancer,
      colon/rectum cancer, gastrointestinal ulcers, diabetes, and appendicitis).
      METHODS: We accessed 2004 and 2011 mortality statistics from the most developed
      cities and least developed rural areas in China using a retrospective design. The
      relative risk of death associated with urbanization and age was quantified using
      Generalized linear model (the exp.(B) from model is interpreted as the risk
      ratio; the greater the B, the greater the impact of urbanized factors or aging
      factor or effect of aging factor with urbanization). The interaction between
      region (cities and rural areas) and age was considered as indicator to assess
      role of age in mortality with urbanization. RESULTS: Greater risk of disease with
      urbanization were, in ascending order, for diabetes, colon/rectum cancer,
      hepatitis C and pancreas cancer. Stronger the effect of aging with urbanization
      were, in ascending order, for stomach cancer, ulcer, liver cancer, colon/rectum
      cancer, pancreas cancer, diabetes, hepatitis C, appendicitis and diarrhea. When
      the effects of aging and urbanization on diseases were taken together as the
      dividing value, we were able to further divide the 12 gastrointestinal diseases
      into three groups to guide the development of medical strategies. CONCLUSIONS: It
      was suggested that mortality rate for most gastrointestinal diseases was
      sensitive to urbanization and control of external risk factors could lead to the
      conversion of most gastrointestinal disease.

PMID- 30285654
TI  - A first CLN6 variant case of late infantile neuronal ceroid lipofuscinosis caused
      by a homozygous mutation in a boy from China: a case report.
AB  - BACKGROUND: Neuronal ceroid lipofuscinosis (NCLs) are lysosomal storage disorders
      characterized by seizures, motor impairment, and loss of vision. Ceroid
      lipofuscinosis (CLN) gene mutations are the cause, but NCL cases arising from
      CLN6 mutations have not been described in China to date. The CLN6 protein, which
      plays a role in lysosomal function, is an endoplasmic reticulum (ER) membrane
      protein with seven transmembrane (TM) domains. It has a cytosolic-facing amino
      terminal domain and a luminal-facing carboxyl terminal domain, with six loops
      between the TM domains. CASE PRESENTATION: Here we report a case involving a
      Chinese boy whose suspected diagnosis was a hereditary leukoencephalopathy, based
      on brain MRI imaging and epilepsy symptoms, language articulation disorders,
      ataxia, and unstable gait. The electroencephalogram showed epileptic discharges,
      and the brain MRI scan showed high signal intensity adjacent to the bilateral
      posterior horns of the lateral ventricles on T2-weighted images, along with
      cerebellar atrophy. Using next-generation sequencing for the genes in a panel for
      hereditary leukoencephalopathies, we detected a homozygous missense point
      mutation c.892G > A(p.Glu298Lys) in CLN6, and the variant was interpreted as
      pathogenic on in silico analysis. Absence of this mutation was confirmed in 259
      controls. Late infantile NCL and secondary epilepsy were diagnosed, and oral
      sodium valproate was prescribed. The epilepsy was not well controlled, however,
      and the other signs had not improved at the 6-month follow-up. We also analyzed
      the loci of 31 CLN6 missense mutations, including those previously reported and
      the current one. We found that 22.6% (7/31) of the mutations are in the
      cytoplasmic domains, about 32.2% (10/31) are in the TM domains, and about 45.2%
      (14/31) are in the luminal domains. These mutations were mostly located in the
      TM3-TM4 loop (6/31), TM1-TM2 loop (4/31), and C-terminus (4/31), with none found
      in the TM4-TM5 loop, TM5-TM6 loop, or TM7. CONCLUSIONS: We report the first case
      in China of NCL caused by a CLN6 mutation, expanding the genotype options for
      NCLs. In practice, NCLs generally are not the initial suspected diagnosis for
      such cases. Use of a gene sequencing panel for investigating unexplained seizures
      or leukoencephalopathies can help confirm the diagnosis.

PMID- 30285653
TI  - Development of a sandwich ELISA to detect Leishmania 40S ribosomal protein S12
      antigen from blood samples of visceral leishmaniasis patients.
AB  - BACKGROUND: Visceral leishmaniasis (VL), caused by Leishmania donovani complex
      parasites, is a neglected parasitic disease that is generally fatal if untreated.
      Despite decades of research to develop a sensitive VL diagnostic test, definitive
      diagnosis of VL still mainly relies on the visualization of the parasite in
      aspirates from the spleen, liver or bone marrow, an invasive and dangerous
      process with variable sensitivity. A sensitive assay that can detect Leishmania
      antigen from blood samples will help confirm cause, cure or recurrence of VL.
      METHODS: In this study, rabbit polyclonal antibodies were raised against eight
      recombinant Leishmania proteins that are highly abundant in Leishmania. The
      antibodies were purified and labeled with biotin for developing a prototype
      sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The ELISA for the
      Leishmania 40S ribosomal protein S12 detected target antigen with the highest
      sensitivity and specificity and could detect 1 pg of purified protein or as few
      as 60 L. donovani parasites. The 40S ribosomal protein S12 sandwich ELISA could
      detect the target antigen from Peripheral Blood Mononuclear Cell (PBMC) samples
      in 68% of VL patients and post-kala-azar dermal leishmaniasis (PKDL) patients,
      providing an estimation of parasitemia ranging from 15 to 80 amastigotes per ml
      of blood. CONCLUSION: These results indicate that the 40S ribosomal protein S12
      sandwich ELISA warrants further tests with more clinical samples of VL patients
      and other parasitic diseases. It is hopeful that this ELISA could become a useful
      tool for confirming VL diagnosis, monitoring treatment progress, disease
      recurrence and possibly detecting asymptomatic Leishmania infections with a high
      parasite load.

PMID- 30285655
TI  - Long-term survival in Japanese renal transplant recipients with Alport syndrome:
      a retrospective study.
AB  - BACKGROUND: Patients with Alport syndrome (AS) develop progressive kidney
      dysfunction due to a hereditary type IV collagen deficiency. Survival of the
      kidney allograft in patients with AS is reportedly excellent because AS does not
      recur. However, several studies have implied that the type IV collagen in the GBM
      originates from podocytes recruited from the recipient's bone marrow-derived
      cells, suggesting the possibility of AS recurrence. Limited data are available
      regarding AS recurrence and graft survival in the Japanese population; the vast
      majority were obtained from living related kidney transplantation (LRKTx).
      METHODS: In this retrospective study, twenty-one patients with AS were compared
      with 41 matched patients without AS from 1984 to 2015 at two centers using
      propensity scores. Nineteen of the 21 patients with AS underwent LRKTx. The mean
      post-transplant follow-up period was 83 months in the AS group and 110 months in
      the control group. Histopathological AS recurrence was assessed by
      immunoreactivity of alpha5 (type IV collagen) antibody and electron microscopy.
      RESULTS: The graft survival rate was equivalent between patients with and without
      AS (86.7% vs. 77.1% and 69.3% vs. 64.2% at 5 and 10 years; p = 0.16, log-rank
      test). Immunoreactivity to alpha5 antibody showed strong linear positivity with
      no focal defect in six patients. Electron microscopy showed no GBM abnormalities
      in two patients who were exhibiting long-term kidney allograft survival.
      CONCLUSIONS: We confirmed that alpha5 and the GBM structure were
      histopathologically maintained in the long term after kidney transplantation. The
      patient and graft survival rates were equivalent between Japanese patients with
      and without AS.

PMID- 30285656
TI  - Prognostic value of the fibrinogen/albumin ratio (FAR) in patients with operable
      soft tissue sarcoma.
AB  - BACKGROUND: Coagulation and nutrition play important roles in cancer progression.
      The aim of the present study is to evaluate the prognostic value of the
      preoperative fibrinogen/albumin ratio (FAR) in surgical patients with soft tissue
      sarcoma (STS) and to compare this value with other inflammatory biomarkers. In
      addition, we investigated the relationship between FAR and the
      clinicopathological characteristics of STS patients. METHODS: We included 310 STS
      patients in this retrospective study. Kaplan-Meier curves, univariate and
      multivariate Cox proportional models were used in the prognostic analyses.
      RESULTS: According to the receiver operating characteristic (ROC) analysis, the
      optimal FAR cut-off value was 0.0726. The FAR exhibited a greater area under the
      curve (AUC) value (0.680) than did the NLR and PLR. An elevated FAR (>=0.0726)
      was significantly associated with an old age, large tumor size, deep tumor
      location, high tumor grade, and advanced American Joint Committee on Cancer
      (AJCC) stage. Patients with an increased FAR had a shorter median survival time
      and a lower 5-year overall survival (OS) rate than did those with a low FAR (61.0
      vs115.8 months, P < 0.001; 56.7% vs 82.4%, P < 0.001, respectively). Multivariate
      analysis indicated FAR (Hazard ratio (HR) 1.907, 95% confidence interval (CI)
      1.161-3.132, P < 0.001) to be an independent prognostic factor for OS, as were
      tumor depth, grade and PLR. CONCLUSIONS: Preoperative FAR is associated with
      tumor progression and can be considered an independent factor for OS of resected
      STS patients.

PMID- 30285657
TI  - Chronic active Epstein-Barr virus infection of T-cell type, systemic form in an
      African migrant: case report and review of the literature on diagnostics
      standards and therapeutic options.
AB  - BACKGROUND: Chronic active Epstein-Barr virus (EBV) infection (CAEBV) of the T
      /NK-cell type, systemic form is a rare and potentially life-threatening illness
      caused by persistent EBV infection. The highest incidence is found in children
      and adolescents with increased frequency among Asians and Native Americans, while
      the disease is uncommon in Western countries. Typically patients present with
      unspecific symptoms, like fever, lymphadenopathy, hepatosplenomegaly and liver
      dysfunction. Due to fatal complications including hemophagocytic syndrome,
      coagulopathy, multiple organ failure and development of EBV-positive
      lymphoproliferative disease (LPD) or lymphoma early diagnosis is critical for
      successful treatment. However, in consequence of the lack of experience due to
      the low incidence in Europe, a broad spectrum of clinical manifestations and a
      particularly unexpected group of patients, diagnosis can be challenging. Inhere
      we describe the clinicopathological findings of an African adult with CAEBV
      associated LPD with a brief review of the literature. CASE PRESENTATION: A 42
      year-old African man with fever, enlargement of the spleen and a suspected
      epileptic seizure was referred to our hospital. Diagnostic testing repeatedly
      revealed a massive EBV-DNA load in peripheral blood. Whole-body PET-CT-scan
      presented a strong uptake at multiple bone marrow sites, the thyroid and the
      adrenal glands. Histopathological analysis of bone marrow and thyroid gland
      revealed a highly proliferating, atypical and predominantly intravascular
      cytotoxic T-cell population with intracellular EBV-encoded RNA. Clonality
      analysis revealed the presence of polyclonal T-cell-receptor. Based on these
      findings a CAEBV of the T-/NK-cell type, systemic form was diagnosed. Subsequent
      therapy including three cycles of chemotherapy with cyclophosphamide,
      doxorubicin, vincristine and prednisolone resulted in decreased EBV load,
      clinical improvement and ongoing complete remission. CONCLUSION: Adult-onset
      CAEBV of T/NK-cell type usually comprises a poor prognosis and is extremely rare
      in Western countries. Therefore, our case highlights the need for a clinical
      awareness of this disease in patients with systemic illness and for a
      comprehensive multidisciplinary diagnostic approach to facilitate diagnosis.
      Treatment options include antiviral drugs, immunosuppressive agents and systemic
      chemotherapy with or without allogeneic stem cell transplantation. Given the
      limited data these options need to be decided upon in each patient individually
      considering severity of the disease, comorbidities and response.

PMID- 30285658
TI  - Sociocultural determinants of nomadic women's utilization of assisted childbirth
      in Gossi, Mali: a qualitative study.
AB  - BACKGROUND: In sub-Saharan Africa (SSA), nomads account for 30 to 60 million
      people. Their mobility, due to a constant search for pastures and water points,
      makes health services less accessible to them. Few nomadic women use assisted
      delivery, which increases the risk of maternal mortality. The reasons behind this
      limited use have been poorly documented. The objective of this study was to
      understand the sociocultural determinants of assisted childbirth by nomadic
      women. METHODS: We conducted a qualitative research in the health area of Gossi
      (Mali), mainly populated by nomads. Data were collected through a literature
      review, 26 semi-structured interviews, a non-participant observation, and a
      logbook. Nomadic women who gave birth in the past three months were included in
      the study, whether they used assisted delivery or not. A thematic content
      analysis was performed with QDA Miner software. RESULTS: The study identified a
      complex combination of determinants resulting in the use or non-use of assisted
      childbirth by the nomads of Gossi. Several participants recognized the value of
      assisted delivery but gave birth at home. They identified sociocultural
      determinants related to their representations and bodily experiences; the risks
      and emotions (fear, stress, anxiety) associated with pregnancy; the onset of
      labor and delivery; and their weak autonomy in terms of movement, decision
      making, and economic agency. Nomadic women are not free in their movements, and
      in order to seek care, they require the permission and support of a man (husband,
      brother, or father). Furthermore, the participants are housewives, and men
      control family resources and make decisions regarding all financial matters.
      Assisted delivery is often only considered when there are complications.
      CONCLUSION: This research has made it possible to understand the sociocultural
      determinants of the use of assisted childbirth among nomadic women, which should
      be taken into account when organizing health services for these populations.

PMID- 30285659
TI  - Trends in stroke outcomes in the last ten years in a European tertiary hospital.
AB  - BACKGROUND: Studying the impact of demographic changes and progress in the
      management of stroke patients is necessary in order to organize care structures
      for the coming years. Consequently, we analyzed the prognostic trends of patients
      admitted to the Stroke Unit of a tertiary hospital in the last ten years.
      METHODS: The University Clinical Hospital of Santiago de Compostela is the
      referral hospital for stroke in a catchment area that accounts for 16.5% of the
      population of Galicia. Data from patients admitted to the Stroke Unit were
      registered prospectively. A multinomial logistic regression was performed to
      determine the influence of new trends in demographic factors and in the
      management of patients with acute stroke. For the expected trend of progression,
      a 2008-2011 and 2012-2017 time series model was made by selecting the most
      appropriate model. RESULTS: In the last 10 years, the age of stroke onset has
      only increased in women (from 74.4 +/- 2.2 years in 2008 to 78.8 +/- 2.1 years in
      2017; p = 0.037), and the same happens with the severity of neurological symptoms
      (ischemic stroke (IS), p < 0.0001; from 14 [10, 19] in 2008 to 19 [15, 26] in
      2017), with a higher percentage of cardioembolic strokes (40.7% vs. 32.2% of
      cardioembolic strokes in women vs. men, p < 0.0001). In a multiple linear
      regression model, hospital improvement was mainly associated with the use of
      reperfusion treatment (B 53.11, CI 95% 49.87, 56.36, p < 0.0001). A
      differentiated multinomial logistic regression analysis conducted for the whole
      sample with ischemic strokes in the two time periods (2008-2011 and 2012-2017)
      showed no differences in the influence of factors associated with higher
      morbidity and mortality. The modeling of time series showed a distinct falling
      trend in mortality, with a slight increase in good outcome as well as morbidity
      in both ischemic and hemorrhagic stroke. CONCLUSIONS: Our results showed that
      mortality decreased in the entire sample; however, although outcome at discharge
      improved in ischemic stroke, severe disability also increased in these patients.
      Importantly, this tendency towards increased morbidity seems to be confirmed for
      the coming years.

PMID- 30285660
TI  - A multicenter survey on toxoplasmosis knowledge among pregnant women in Poland
      (the TOWER study).
AB  - BACKGROUND: The seroprevalence of Toxoplasma gondii ranges widely in different
      areas of the world and different populations. Although toxoplasmosis is typically
      benign and asymptomatic, it induces major complications in immunocompromised
      individuals and during pregnancy. Prevention of maternal primary infection
      constitutes the major tool for avoiding congenital T. gondii infections and
      toxoplasmosis complications. The preventive measures depend on the women's
      knowledge about toxoplasmosis. The aim of the study was to assess the knowledge
      on toxoplasmosis among pregnant women in Poland. METHODS: The study was conducted
      between October 2016 and January 2017 in 3 Polish cities. During a visit in a
      hospital outpatient clinic, pregnant women aged > 16 years fulfilled a previously
      validated questionnaire. The questions concerned personal data (age, parity,
      educational level, place of residence), toxoplasmosis knowledge (etiology, routes
      of transmission, symptoms, sequelae), and sources consulted to collect
      information. RESULTS: Overall, 465 pregnant women participated in the survey; 439
      (94.4%) were aware of toxoplasmosis. Toxoplasmosis was perceived as a zoonotic
      disease by 77.4%, as a parasitic disease by 41.7%, as a disease transmitted
      through poor hand hygiene by 8.6%, as a childhood illness by 4%, and as a
      congenital disease by 0.4%. Regarding the transmission route, 84.5% of women
      pointed at a domestic cat, 46.7% at eating raw or undercooked meat. The total of
      84.3% did not know toxoplasmosis symptoms, and 12.0% stated that they did not
      present the symptoms. In multivariate analysis, younger age (OR, 2.74; 95% CI,
      1.67-4.49; p <  0.001), city residence (OR, 13.45; 95% CI, 3.12-57.89; p < 
      0.003), and higher education level (OR, 6.81; 95% CI, 3.69-12.59; p <  0.001)
      were significantly associated with better knowledge of toxoplasmosis, and the
      number of children (OR, 0.32; 95% CI, 0.22-0.48; p <  0.001) - with higher
      knowledge of the symptoms. CONCLUSIONS: Among pregnant women in Poland, the basic
      knowledge on toxoplasmosis is very high (94.4%). Younger age, city residence,
      higher education level, and the number of children turned out significantly
      associated with better knowledge of T. gondii and toxoplasmosis symptoms.

PMID- 30285661
TI  - Short term risk of non-fatal and fatal suicidal behaviours: the predictive
      validity of the Columbia-Suicide Severity Rating Scale in a Swedish adult
      psychiatric population with a recent episode of self-harm.
AB  - BACKGROUND: The Columbia-Suicide Severity Rating Scale (C-SSRS) is a relatively
      new instrument for the assessment of suicidal ideation and behaviour that is
      widely used in clinical and research settings. The predictive properties of the C
      SSRS have mainly been evaluated in young US populations. We wanted to examine the
      instrument's predictive validity in a Swedish cohort of adults seeking
      psychiatric emergency services after an episode of self-harm. METHODS:
      Prospective cohort study of patients (n = 804) presenting for psychiatric
      emergency assessment after an episode of self-harm with or without suicidal
      intent. Suicidal ideation and behaviours at baseline were rated with the C-SSRS
      and subsequent non-fatal and fatal suicide attempts within 6 months were
      identified by record review. Logistic regression was used to evaluate separate
      ideation items and total scores as predictors of non-fatal and fatal suicide
      attempts. Receiver operating characteristics (ROC) curves were constructed for
      the suicidal ideation (SI) intensity score and the C-SSRS total score. RESULTS:
      In this cohort, the median age at baseline was 33 years, 67% were women and 68%
      had made at least one suicide attempt prior to the index attempt. At least one
      non-fatal or fatal suicide attempt was recorded during follow-up for 165 persons
      (20.5%). The single C-SSRS items frequency, duration and deterrents were
      associated with this composite outcome; controllability and reasons were not. In
      a logistic regression model adjusted for previous history of suicide attempt, SI
      intensity score was a significant predictor of a non-fatal or fatal suicide
      attempt (OR 1.08; 95% CI 1.03-1.12). ROC analysis showed that the SI intensity
      score was somewhat better than chance in correctly classifying the outcome (AUC
      0.62, 95% CI 0.57-0.66). The corresponding figures for the C-SSRS total score
      were 0.65, 95% CI 0.60-0.69. CONCLUSIONS: The C-SSRS items frequency, duration
      and deterrents were associated with elevated short term risk in this adult
      psychiatric cohort, as were both the SI intensity score and the C-SSRS total
      score. However, the ability to correctly predict future suicidal behaviour was
      limited for both scores.

PMID- 30285662
TI  - PD-L1/PD-1 crosstalk in colorectal cancer: are we targeting the right cells?
AB  - BACKGROUND: The analysis of tumour-infiltrating immune cells within patients'
      tumour samples in colorectal cancer (CRC) has become an independent predictor of
      patient survival. The tumour microenvironment and the immune checkpoints, such as
      PD-L1/PD-1, are relevant to the prognoses and also appear to be relevant for
      further CRC therapies. METHODS: We analysed the presence and features of the
      infiltrated monocyte/macrophage and lymphocyte populations in both tumour and
      peritumour samples from patients with CRC (n = 15). RESULTS: We detected a large
      number of CD14+ monocytes/macrophages with an alternative phenotype (CD64+CD163+)
      and CD4+ lymphocytes that infiltrated the tumour, but not the peritumour area.
      The monocytes/macrophages expressed PD-L1, whereas the lymphocytes were PD-1+;
      however, we did not find high PD-L1 levels in the tumour cells. Coculture of
      circulating naive human monocytes/macrophages and lymphocytes with tumour cells
      from patients with proficient mismatch repair CRC induced both an alternative
      phenotype with higher expression of PD-L1 in CD14+ cells and the T-cell
      exhaustion phenomenon. The addition of an alpha-PD-1 antibody restored lymphocyte
      proliferation. CONCLUSION: These results emphasise the interesting nature of
      immune checkpoint shifting therapies, which have potential clinical applications
      in the context of colorectal cancer.

PMID- 30285663
TI  - Neurological signs as early determinants of dementia and predictors of mortality
      among older adults in Latin America: a 10/66 study using the NEUROEX assessment.
AB  - BACKGROUND: Neurodegenerative processes in the elderly damage the brain, leading
      to progressive, incapacitating cognitive, behavioral, and motor dysfunctions
      which culminate in dementia. Fully manifest dementia is likely to be preceded by
      the presence of neurological signs, which could serve as early determinants of
      dementia and predictors of mortality. The aims of this study were to assess the
      construct validity of a neurological battery assessed among older adults living
      in Latin America, and to test the association of groups of neurological signs
      with dementia cross-sectionally, and mortality longitudinally. METHODS: The 10/66
      Dementia Research Group collected information on neurological symptoms via the
      NEUROEX assessment in population based surveys of older adults living in low and
      middle-income countries. Data from 10,856 adults participating in the baseline
      assessment of the 10/66 study and living in Cuba, Dominican Republic, Peru,
      Venezuela and Mexico were analysed. Exploratory and confirmatory analysis were
      used to explore dimensionality of neurological symptoms. Poisson regression
      analyses were used to link groups of neurological signs with dementia at
      baseline. Cox hazard regression models were used to explore the predictive
      validity of neurological signs with mortality at follow up. RESULTS: Exploratory
      and confirmatory factor analyses revealed four dimensions of neurological signs,
      which are associated with lesions of specific brain regions. The identified
      factors showed consistency with groups of neurological signs such as frontal,
      cerebellar, extrapyramidal, and more generalized gait disturbance signs.
      Regression analyses revealed that all groups of neurological signs were
      positively associated with dementia at baseline and predicted mortality at follow
      up. CONCLUSIONS: Our findings support the construct and predictive validity of
      the NEUROEX assessment, linking neurological and gait impairments with dementia
      at baseline, and with mortality at follow up among older adults living in five
      Latin American countries.

PMID- 30285664
TI  - The rs2147578 C > G polymorphism in the Inc-LAMC2-1:1 gene is associated with
      increased neuroblastoma risk in the Henan children.
AB  - BACKGROUND: The rs2147578 C > G polymorphism in the long non-coding RNA gene Lnc
      LAMC2-1:1 is associated with increased susceptibility to a few types of cancers.
      However, its role in neuroblastoma has not been evaluated yet. METHODS: We
      investigated the association between the lnc-LAMC2-1:1 rs2147578 C > G
      polymorphism and neuroblastoma susceptibility in Chinese Han populations. A total
      of 393 neuroblastoma cases and 812 healthy individuals from the Henan and
      Guangdong provinces were enrolled and subjected to genotyping. Odds ratio (OR)
      and 95% confidence interval (CI) were used to determine the strength of the
      association of interest. RESULTS: Combined analysis revealed that the lnc-LAMC2
      1:1 rs2147578 C > G polymorphism was associated with increased neuroblastoma
      susceptibility (CG vs. CC: adjusted OR = 1.33, 95% CI = 1.01-1.75, P = 0.045;
      CG/GG vs. CC: adjusted OR = 1.34, 95% CI = 1.03-1.74, P = 0.028). In
      stratification analysis, children under 18 months with rs2147578 CG/GG genotypes
      had an increased neuroblastoma risk (adjusted OR = 1.70, 95% CI = 1.08-2.67, P =
      0.022). Females with rs2147578 CG/GG genotypes also had increased neuroblastoma
      susceptibility (adjusted OR = 2.08, 95% CI = 1.37-3.18, P = 0.0007). In addition,
      children with lnc-LAMC2-1:1 rs2147578 CG/GG genotypes were prone to develop
      earlier stages of neuroblastoma (adjusted OR = 1.46, 95% CI = 1.01-2.12, P =
      0.046). CONCLUSIONS: The Lnc-LAMC2-1:1 rs2147578 C > G polymorphism may
      contribute to increased neuroblastoma susceptibility in children of Henan
      province.

PMID- 30285665
TI  - Correction to: Reasons for lithium discontinuation in men and women with bipolar
      disorder: a retrospective cohort study.
AB  - Following publication of the original article [1], the authors reported an error
      in Fig. 1 and Table 1, concerning the number of female participants. The correct
      number is 283, instead of 238 that was originally published.

PMID- 30285666
TI  - Health utility scores of family caregivers for leukemia patients measured by EQ
      5D-3L: a cross-sectional survey in China.
AB  - BACKGROUND: This study assessed the health related quality of life of family
      caregivers (FCs) of leukemia patients by using the health utility scores derived
      from the EuroQol five-dimensional (EQ-5D) questionnaire. METHODS: A cross
      sectional survey was undertaken on 306 family caregivers of leukemia patients to
      assess their health utility using the EQ-5D-3L. Participants were recruited from
      three hospitals in China's Heilongjiang province. The health utility scores of
      the participants were estimated based on the Chinese EQ-5D-3L value set and
      compared with those of the local general population. Factors predicting the
      health utility scores were identified through the Kruskal-Wallis analysis of
      variance and median regression analyses. RESULTS: FCs had lower health utility
      scores than the general population (p < 0.001). The participants with a lower
      socioeconomic status had lower utility scores and reported more problems than
      those with a higher socio-economic status. Better family function and higher
      social support were associated with higher health utility scores. The type of
      leukemia, household income, and social support are significant predictors of
      health utility scores of the FCs. Chronic lymphocytic leukemia, low socio
      economic status, and low social support are associated with lower health utility
      scores of the FCs. CONCLUSIONS: FCs for leukemia patients have lower health
      utility scores than the local general population, as measured by the EQ-5D-3L.
      There is an immediate need to address the health concerns of FCs, who play an
      important role in the Chinese health care system.

PMID- 30285667
TI  - Prevalence and associated factors of pediatric emergency mortality at Tikur
      Anbessa specialized tertiary hospital: a 5 year retrospective case review study.
AB  - BACKGROUND: Childhood mortality remains high in resource-limited third world
      countries. Most childhood deaths in hospital often occur within the first 24 h of
      admission. Many of these deaths are from preventable causes. This study aims to
      describe the patterns of mortality in children presenting to the pediatric
      emergency department. METHODS: This was a five-year chart review of deaths in
      pediatric patients aged 7 days to 13 years presenting to the Tikur Anbessa
      Specialized Tertiary Hospital (TASTH) from January 2012 to December 2016. Data
      were collected using a pretested, structured checklist, and analyzed using the
      SPSS Version 20. Multivariate analysis by logistic regression was carried out to
      estimate any measures of association between variables of interest and the
      primary outcome of death. RESULTS: The proportion of pediatric emergency
      department (PED) deaths was 4.1% (499 patients) out of 12,240 PED presentations.
      This translates to a mortality rate of 8.2 deaths per 1000 patients per year. The
      three top causes of deaths were pneumonia, congestive heart failure (CHF) and
      sepsis. Thirty two percent of the deaths occurred within 24 h of presentation
      with 6.5% of the deaths being neonates and the most common co-morbid illness was
      malnutrition (41.1%). Multivariate analysis revealed that shortness of breath
      [AOR=2.45, 95% CI (1.22-4.91)], late onset of signs and symptoms [AOR=3.22, 95%
      CI (1.34-7.73)], fever [AOR=3.17, 95% CI (1.28-7.86)], and diarrhea [AOR=3.36,
      95% CI (1.69-6.67)] had significant association with early mortality. CONCLUSION:
      The incidence of pediatric emergency mortality was high in our study. A delay in
      presentation of more than 48 hours, diarrheal diseases and shortness of breath
      were significantly associated with early pediatric mortality. Early
      identification and intervention are required to reduce pediatric emergency
      mortality.

PMID- 30285668
TI  - The prognostic and predictive value of tumor-infiltrating lymphocytes and
      hematologic parameters in patients with breast cancer.
AB  - BACKGROUND: Carcinogenesis and tumor growth are associated with chronic
      inflammation and the host immune system. Here, we investigated the clinical
      significance and relationship between tumor-infiltrating lymphocytes (TILs) and
      hematologic parameters in patients with breast cancer. METHODS: Invasive ductal
      breast cancer patients (N = 145) who underwent surgery were retrospectively
      evaluated. Samples were obtained using a core needle biopsy for CD8+, FOXP3+ TIL
      assessment. Blood lymphocytes, neutrophils, monocytes, and platelets were
      obtained by peripheral venous punctures. RESULTS: CD8 + TILs were significantly
      associated with absolute lymphocyte count (ALC) and the absolute monocyte count
      (AMC). Low LMR (ALC/AMC) (cut-off - 5.3, range = 0.73-12.31) was associated with
      poor overall survival (OS) (p = 0.010), disease-free survival (DFS) (p = 0.005).
      However, in subgroup analysis, LMR did not have any value as a prognostic factor
      in HER2-positive breast cancers. TILs had different prognostic impacts across
      breast cancer subtypes, although they were not statistically significant. The
      treatment response after NAC tended to improve in breast cancer patients with
      high FOXP3+ TILs, low NLR (neutrophil count/ALC) (FOXP3 p for trend = 0.006, NLR
      p for trend = 0.063). CONCLUSIONS: A relevance between TILs and hematologic
      parameters in breast cancer was demonstrated. The influence of the immune system
      on breast cancer progression may differ by subtype.

PMID- 30285669
TI  - Cost analysis of implementing mHealth intervention for maternal, newborn & child
      health care through community health workers: assessment of ReMIND program in
      Uttar Pradesh, India.
AB  - BACKGROUND: The main intervention under ReMiND program consisted of a mobile
      health application which was used by community health volunteers, called ASHAs,
      for counselling pregnant women and nursing mothers. This program was implemented
      in two rural blocks in Uttar Pradesh state of India with an overall aim to
      increase quality of health care, thereby increasing utilization of maternal &
      child health services. The aim of the study was to assess annual & unit cost of
      ReMiND program and its scale up in UP state. METHOD AND MATERIALS: Economic
      costing was done from the health system and patient's perspectives. All resources
      used during designing & planning phase i.e., development of application; and
      implementation of the intervention, were quantified and valued. Capital costs
      were annualised, after assessing their average number of years for which a
      product could be used and accounting for its depreciation. Shared or joint costs
      were apportioned for the time value a resource was utilized under intervention.
      Annual cost of implementing ReMiND in two blocks of UP along and unit cost per
      pregnant woman were estimated. Scale-up cost for implementing the intervention in
      entire state was calculated under two scenarios - first, if no extra human
      resource were employed; and second, if the state government adopted the same
      pattern of human resource as employed under this program. RESULTS: The annual
      cost for rolling out ReMiND in two blocks of district Kaushambi was INR 12.1
      million (US $ 191,894). The annualised start-up cost constituted 9% of overall
      cost while rest of cost was attributed to implementation of the intervention. The
      health system program costs in ReMiND were estimated to be INR 31.4 (US $ 0.49)
      per capita per year and INR 1294 (US $ 20.5) per registered women. The per capita
      incremental cost of scale up of intervention in UP state was estimated to be INR
      4.39 (US $ 0.07) when no additional supervisory staffs were added. CONCLUSION:
      The cost of scale up of ReMiND in Uttar Pradesh is 6% of annual budget for
      'reproductive and child health' line item under state budget, and hence appears
      to be financially sustainable.

PMID- 30285670
TI  - A case report of isolated distal upper extremity weakness due to cerebral
      metastasis involving the hand knob area.
AB  - BACKGROUND: Unilateral weakness of an upper extremity is most frequently caused
      by traumatic nerve injury or compression neuropathy. In rare cases, lesion of the
      central nervous system may result in syndromes suggesting peripheral nerve damage
      by the initial examination. Pseudoperipheral hand palsy is the best known of
      these, most frequently caused by a small lesion in the contralateral motor cortex
      of the brain. The 'hand knob' area refers to a circumscribed region in the
      precentral gyrus of the posterior frontal lobe, the lesion of which leads to
      isolated weakness of the upper extremity mimicking peripheral nerve damage. The
      etiology of this rare syndrome is almost exclusively related to an embolic
      infarction. CASE PRESENTATION: We present the case of a 70-year-old male patient
      with isolated left sided upper extremity weakness and clumsiness without sensory
      disturbance suggesting a lesion of the radial nerve. Nerve conduction studies had
      normal results excluding peripheral nerve damage. Neuroimaging (cranial CT and
      MRI) detected 3 space occupying lesions, one of them in the right precentral
      gyrus. An irregularly shaped tumor was found by CT in the left lung with multiple
      associated lymph node conglomerates. The metastasis from this mucinous tubular
      adenocarcinoma with solid anaplastic parts to the 'hand knob' area was
      responsible for the first clinical sign related to the pulmonary malignancy.
      CONCLUSIONS: Pseudoperipheral palsy of the upper extremity is not necessarily the
      consequence of an embolic stroke. If nerve conduction studies have normal
      results, neuroimaging - preferably MRI - should be performed, as lesion in the
      hand-knob area of the precentral gyrus can also be caused by a malignancy.

PMID- 30285671
TI  - The improved cure fraction for esophageal cancer in Linzhou city.
AB  - BACKGROUND: Survival of esophageal cancer in Linzhou was seen to increase over
      the past few decades and is higher than the average level of China due to the
      implementation of comprehensive prevention and control measures. In population
      based studies, relative survival is a common index to approximate disease
      specific survival. However, the cure fraction maybe great interest to patients
      and physicians. This study aimed to investigate the cure fraction of esophageal
      cancer in Linzou city during 2003-2012 with a cure model. METHODS: We carried out
      a population-based study of 8067 esophageal cancer patients in the Linzhou city
      during 2003-2012. Flexible parametric cure models were used to estimate cure
      proportions and median survival times of uncured by year of diagnosed and age. In
      each model, an interaction between calendar year and age were included. All
      variables in the model were included both as constant and time-varying effects.
      RESULTS: The 5-year relative survival rate was increased in every age group from
      2003 to 2012. The huge increase in the cure proportion was observed in each age
      group. At the year of 2011-2012, 79.8%, 58.0%, 123.4% and 162.7% improvements of
      cure proportion were seen in age group 19-49, 50-59, 60-69 and 70-99 years
      compared with year of 2003-2004. Meanwhile, survival of 'uncured' patients
      changed little in all age group. CONCLUSIONS: The improvement of survival in
      Linzhou city during 2003-2012 was mainly due to an increasing cure proportion.
      Huge improvement of cure fraction within short period is likely due to the
      organized screening of esophageal cancer in Linzhou city.

PMID- 30285674
TI  - The effectiveness of high-intensity CBT and counselling alone and following low
      intensity CBT: a reanalysis of the 2nd UK National Audit of Psychological
      Therapies data.
AB  - BACKGROUND: A previously published article in this journal reported the service
      effects from 103 services within the UK Improving Access to Psychological
      Therapies (IAPT) initiative and the comparative effectiveness of CBT and
      Counselling provision. All patients received High-intensity CBT or High-intensity
      Counselling, but some also received Low-intensity CBT before being stepped-up to
      High intensity treatments. The report did not distinguish between patients who
      received low-intensity CBT before being stepped-up. This article clarifies the
      basis for collapsing low- and high-intensity interventions by analysing the four
      treatment conditions separately. METHOD: Data from 33,243 patients included in
      the second round of the National Audit of Psychological Therapies (NAPT) were re
      analysed as four separate conditions: High-intensity CBT only (n = 5975); High
      intensity Counselling only (n = 3003); Low-intensity CBT plus High-intensity CBT
      (n = 17,620); and Low-intensity CBT plus High-intensity Counselling (n = 6645).
      Analyses considered levels of pre-post therapy effect sizes (ESs), reliable
      improvement (RI) and reliable and clinically significant improvement (RCSI).
      Multilevel modelling was used to model predictors of outcome, namely patient pre
      post change on PHQ-9 scores at last therapy session. RESULTS: Significant
      differences obtained on various outcome indices but were so small they carried no
      clinical significance. Including the four treatment groups in a multilevel model
      comprising patient intake severity, patient ethnicity and number of sessions
      attended showed no significant differences between the four treatment groups.
      Comparisons between the two high-intensity interventions only (N = 8978)
      indicated Counselling showed more improvement than CBT by 0.3 of a point on PHQ-9
      for the mean number of sessions attended. However, this result was moderated by
      the number of sessions and for 12 or more sessions, the advantage went to CBT.
      CONCLUSIONS: This re-analysis showed no evidence of clinically meaningful
      differences between the four treatment conditions using standard indices of
      patient outcomes. However, a differential advantage to high-intensity Counselling
      for fewer than average sessions attended and high-intensity CBT for more than
      average sessions attended has important service implications. The finding of
      equivalent outcomes between high-intensity CBT and Counselling for more severe
      patients also has important policy implications. Empirically-informed procedures
      (e.g., predictive modelling) for assigning patients to interventions need to be
      considered to improve patient outcomes.

PMID- 30285673
TI  - Study on safety of laparoscopic total gastrectomy for clinical stage I gastric
      cancer: the protocol of the CLASS02-01 multicenter randomized controlled clinical
      trial.
AB  - BACKGROUND: The safety of laparoscopic total gastrectomy (LTG) for the treatment
      of gastric cancer remains lack of clinical evidence. The Chinese Laparoscopic
      Gastrointestinal Surgery Study (CLASS) Group recently launched a multicenter
      randomized clinical trial (CLASS02-01) to compare the safety of LTG for clinical
      stage I gastric cancer with the conventional open total gastrectomy (OTG).
      METHODS: This CLASS02-01 trial is a prospective, multicenter, randomized,
      controlled, open, and non-inferiority trial. Two hundred patients who met the
      inclusion criteria and did not accord with the exclusion criteria will be
      randomly divided into LTG group (n = 100) and OTG group (n = 100). The primary
      purpose of this study is to evaluate the early operative morbidity and mortality
      of LTG compared with OTG for clinical stage I gastric adenocarcinoma. The second
      purpose is to evaluate the recovery course and compare the postoperative hospital
      stay of the patients enrolled in this study. DISCUSSION: This CLASS02-01 trial is
      the first prospective randomized two-arm controlled study to determine the safety
      of LTG compared with OTG. Through this trial, we hope to show that experienced
      surgeons can safely perform LTG with lymphadenectomy for gastric cancer. TRIAL
      REGISTRATION: ClinicalTrials.gov ID: NCT03007550 . December 30, 2016.

PMID- 30285672
TI  - A pragmatic randomized controlled trial of group transdiagnostic cognitive
      behaviour therapy for anxiety disorders in primary care: study protocol.
AB  - BACKGROUND: Anxiety disorders are the most common mental disorders in community
      settings, and they are associated with significant psychological distress,
      functional and social impairment. While cognitive behaviour therapy (CBT) is the
      most consistently efficacious psychological treatment for anxiety disorders,
      barriers preclude widespread implementation of CBT in primary care.
      Transdiagnostic group CBT (tCBT) focuses on cognitive and behavioural processes
      and intervention strategies common to different anxiety disorders, and could be a
      promising alternative to conventional CBT. This study aims to examine the
      effectiveness of a transdiagnostic group CBT for anxiety disorders program as a
      complement to treatment-as-usual (TAU) in primary mental health care.
      METHODS/DESIGN: The trial is a multicentre pragmatic randomized controlled trial
      with a pre-treatment, post-treatment, and follow-up at 4, 8 and 12-months design.
      Treatment and control groups. a) tCBT (12 weekly 2-h group sessions following a
      manualized treatment protocol); b) TAU for anxiety disorders. Inclusion criteria
      comprise meeting DSM-5 criteria for primary Panic Disorder, Agoraphobia, Social
      Anxiety Disorder and/or Generalized Anxiety Disorder. Patients are recruited in
      three regions in the province of Quebec, Canada. The primary outcome measures are
      the self-reported Beck Anxiety Inventory and the clinician-administered Anxiety
      and Related Disorders Interview Schedule for DSM-5 (ADIS-5); secondary outcome
      measures include treatment responder status based on the ADIS-5, and self
      reported instruments for specific anxiety and depression symptoms, quality of
      life, functioning, and service utilisation. STATISTICAL ANALYSIS: Intention-to
      treat analysis. A mixed effects regression model will be used to account for
      between- and within-subject variations in the analysis of the longitudinal
      effects of the intervention. DISCUSSION: This rigorous evaluation of tCBT in the
      real world will provide invaluable information to decision makers, health care
      managers, clinicians and patients regarding the effectiveness of the
      intervention. Widespread implementation of tCBT protocols in primary care could
      lead to better effectiveness, efficiency, access and equity for the large number
      of patients suffering from anxiety disorders that are currently not obtaining
      evidence-based psychotherapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02811458
      .

PMID- 30285675
TI  - Comparative effectiveness of beta-interferons and glatiramer acetate for
      relapsing-remitting multiple sclerosis: systematic review and network meta
      analysis of trials including recommended dosages.
AB  - BACKGROUND: We systematically reviewed the comparative effectiveness of
      injectable beta-interferons (IFN-beta) and glatiramer acetate (GA) on annualised
      relapse rate (ARR), progression and discontinuation due to adverse events (AEs)
      in RRMS, using evidence from within the drugs' recommended dosages. METHODS: We
      updated prior comprehensive reviews, checked references of included studies,
      contacted experts in the field, and screened websites for relevant publications
      to locate randomised trials of IFN-beta and GA with recommended dosages in RRMS
      populations, compared against placebo or other recommended dosages. Abstracts
      were screened and assessed for inclusion in duplicate and independently. Studies
      were appraised using the Cochrane risk of bias tool. Rate ratios for ARR, hazard
      ratios for time to progression, and risk ratios for discontinuation due to AEs
      were synthesised in separate models using random effects network meta-analysis.
      RESULTS: We identified 24 studies reported in 42 publications. Most studies were
      at high risk of bias in at least one domain. All drugs had a beneficial effect on
      ARR as compared to placebo, but not compared to each other, and findings were
      robust to sensitivity analysis. We considered time to progression confirmed at 3
      months and confirmed at 6 months in separate models; while both models suggested
      that the included drugs were effective, findings were not consistent between
      models. Discontinuation due to AEs did not appear to be different between drugs.
      CONCLUSIONS: Meta-analyses confirmed that IFN-beta and GA reduce ARR and
      generally delay progression as defined in these trials, though there was no clear
      'winner' across outcomes. Findings are additionally tempered by the high risk of
      bias across studies, and the use of an impairment/mobility scale to measure
      disease progression. Future research should consider more relevant measures of
      disability and, given that most trials have been short-term, consider a
      longitudinal approach to comparative effectiveness. REVIEW REGISTRATION: PROSPERO
      CRD42016043278 .

PMID- 30285676
TI  - Cerebral granulomatosis as a manifestation of Crohn's disease.
AB  - BACKGROUND: Crohn's disease (CD) is associated with a variety of extra-intestinal
      manifestations. Most commonly these involve the eye, skin, joints, coagulation
      system and liver. Cerebral manifestations of CD have been reported to a far
      lesser extent. The extensive detrimental impact of neurological symptoms on a
      patient's quality of life makes an early diagnosis and treatment particularly
      important. In previous case-reports, diagnosis of cerebral manifestations in CD
      often relied upon magnetic resonance imaging (MRI) and computed tomography (CT)
      alone. To our knowledge, only one case-report has documented a histologically
      confirmed case of cerebral lesions associated with CD so far. CASE PRESENTATION:
      A 39-year-old right-handed woman with a history of CD was referred to our
      hospital with etiologically unexplained Gadolinium (Gd)-enhancing cortical
      lesions, triggering epileptic seizures. A CT-scan of the thorax and
      bronchoalveolar lavage found no signs of sarcoidosis. Lumbar punctures and
      laboratory testing found no underlying infection or coincidental autoimmune
      disorders and MRI-scans showed progression of lesion load. Consequently, the
      patient underwent stereotactic biopsy of a cortical lesion. Histological
      examination revealed a mixed lympho-histiocytic and tuberculoid granulomatous
      inflammation surrounding small vessels and no signs for infection. After
      exclusion of other granulomatous diseases and the typical histological findings
      we diagnosed a cerebral granulomatosis as a manifestation of CD. The patient was
      initially started on azathioprine, which had to be switched to corticosteroids
      and methotrexate because of an azathioprine related pancreatitis. The patient has
      not suffered any further epileptic seizures to date. CONCLUSION: Cerebral
      manifestation of CD is a possibly underreported entity that may respond well to
      immunosuppressive treatment. In contrast to earlier reports of cerebral
      manifestations in CD, our patient showed no coincident gastrointestinal symptoms
      indicating an activity of CD during the progression of cortical lesion load,
      suggesting that similar to other extra-intestinal manifestations in CD, the
      activity of gastrointestinal symptoms does not necessarily reflect the activity
      of CD associated cerebral vasculitis. Therefore, diagnosis and therapy of
      cerebral manifestation may be delayed when focusing on gastrointestinal symptoms
      alone.

PMID- 30285677
TI  - Profiling the B/T cell receptor repertoire of lymphocyte derived cell lines.
AB  - BACKGROUND: Clonal VDJ rearrangement of B/T cell receptors (B/TCRs) occurring
      during B/T lymphocyte development has been used as a marker to track the
      clonality of B/T cell populations. METHODS: We systematically profiled the B/T
      cell receptor repertoire of 936 cancer cell lines across a variety of cancer
      types as well as 462 Epstein-Barr Virus (EBV) transformed normal B lymphocyte
      lines using RNA sequencing data. RESULTS: Rearranged B/TCRs were readily detected
      in cell lines derived from lymphocytes, and subclonality or potential biclonality
      were found in a number of blood cancer cell lines. Clonal BCR/TCR rearrangements
      were detected in several blast phase CML lines and unexpectedly, one gastric
      cancer cell line (KE-97), reflecting a lymphoid origin of these cells. Notably,
      clonality was highly prevalent in EBV transformed B lymphocytes, suggesting
      either transformation only occurred in a few B cells or those with a growth
      advantage dominated the transformed population through clonal evolution.
      CONCLUSIONS: Our analysis reveals the complexity and heterogeneity of the BCR/TCR
      rearrangement repertoire and provides a unique insight into the clonality of
      lymphocyte derived cell lines.

PMID- 30285679
TI  - Physical Literacy Knowledge Questionnaire: feasibility, validity, and reliability
      for Canadian children aged 8 to 12 years.
AB  - BACKGROUND: Physical literacy is defined as the motivation, confidence, physical
      competence, and knowledge and understanding to engage in physical activity for
      life. Physical literacy knowledge and understanding encompasses movement (how to
      move), performance (evaluation of movement), and health and fitness (value of
      exercise, need for relaxation and sleep, etc.). This paper describes the
      development and evaluation of a standardized assessment of physical literacy
      knowledge and understanding for Canadian children in grades 4, 5, and 6. METHODS:
      Proposed Physical Literacy Knowledge Questionnaire (PLKQ) content was identified
      through expert consultation and a review of provincial/territorial physical
      education curricula for grades 4 to 6. Open-ended questions verified language and
      generated response options. Feasibility was assessed via completion time and
      error frequency. Item validity assessed scores by age, gender, and teacher
      ratings of student knowledge. Test-retest reliability was assessed over short (2
      day) and long (7-day) intervals. RESULTS: Subsets of 678 children (54% girls,
      10.1 +/- 1.0 years of age) completed the feasibility and validity assessments.
      Response errors (missing or duplicate responses, etc.) were minimal (2% or less)
      except for one question (7% error) about the use of safety gear during physical
      activity. A Delphi process among experts in children's physical activity and
      fitness achieved consensus on the core content and supported an item analysis to
      finalize item selection. As expected, knowledge scores increased with age
      (partial eta2 = 0.07) but were not related to gender (p = 0.63). Teacher ratings
      of children's knowledge of physical activity behaviour (r = 0.13, p = 0.01) and
      fitness (r = 0.12, p = 0.03), but not movement skill (r = 0.07, p = 0.19) were
      associated with PLKQ scores. Test-retest reliability for PLKQ score and
      individual questions was substantial to excellent for 71% of comparisons over a 2
      day interval, but lower over a 7-day interval (53% substantial or excellent).
      Items with low reliability had high or low proportions of correct responses.
      CONCLUSIONS: This study provides feasibility and validity evidence for the
      Physical Literacy Knowledge Questionnaire as an assessment of physical literacy
      knowledge for Canadian children in grades 4, 5, and 6. Completion rates were high
      and knowledge scores increased with age. Streamlining of the content in
      accordance with Delphi panel recommendations would further enhance feasibility,
      but would also focus the content on items with limited reliability. Future
      studies of alternative item wording and responses are recommended to enhance test
      retest reliability.

PMID- 30285680
TI  - Choice architecture modifies fruit and vegetable purchasing in a university
      campus grocery store: time series modelling of a natural experiment.
AB  - BACKGROUND: In developed countries, adolescent and young adult diets have been
      found to be nutritionally poor. The aim of this study was to examine whether a
      choice architecture intervention, re-arrangement of produce within a grocery
      store to increase the accessibility of fruit and vegetables, affected purchasing
      behaviour on a university campus. METHODS: A database of daily sales data from
      January 2012 to July 2017 was obtained from a campus grocery store. Two changes
      to the layout were made during this time period. In January 2015, fruit and
      vegetables were moved from the back of the store, furthest from the entrance, to
      the aisle closest to the entrance and an entrance-facing display increasing their
      accessibility. In April 2016, the entrance-facing display of fruit and vegetables
      was replaced with a chiller cabinet so that fruit and vegetables remained more
      accessible than during the baseline period, but less accessible than in the
      period immediately previously. A retrospective interrupted time series analysis
      using dynamic regression was used to model the data and to examine the effect of
      the store re-arrangements on purchasing. All analyses were carried out both for
      sales-by-quantity and for sales-by-money. RESULTS: The first shop re-arrangement
      which made fruit and vegetables more prominent, increased the percentage of total
      sales that were fruit and vegetables, when analysed by either items purchased or
      money spent. The second rearrangement also had a positive effect on the
      percentage of total sales that were fruit and vegetables compared to baseline,
      however this was not significant at the 5% level. Over the five year period, the
      percentage of sales that were fruit and vegetables declined both in terms of
      items purchased, and money spent. CONCLUSIONS: Increasing accessibility of fruit
      and vegetables in a grocery store is a feasible way to improve the diet of
      students in tertiary education. There is evidence of declining fruit and
      vegetable consumption among the studied population, which should be further
      investigated.

PMID- 30285681
TI  - A cross-sectional study exploring the relationship between age, gender, and
      physical measures with adequacy in and predilection for physical activity.
AB  - BACKGROUND: Physical literacy is a complex construct influenced by a range of
      physical, behavioural, affective, and cognitive factors. Researchers are
      interested in relationships among these constituent factors. The purpose of this
      study was to investigate how age, gender, and physical competence components of
      physical literacy relate to a child's adequacy in and predilection for physical
      activity. METHODS: A sample of 8530 Canadian youth (50% girl) aged 8.0 to 12.9
      years participated in the study. Participants completed the Canadian Assessment
      of Physical Literacy (CAPL) protocol, which assesses physical literacy in four
      domains: Physical Competence, Daily Behaviour, Motivation and Confidence, and
      Knowledge and Understanding. Stepwise multiple regression analyses were conducted
      to investigate the relationship between physical competence components of
      physical literacy (Progressive Aerobic Cardiovascular Endurance Run [PACER],
      Canadian Agility and Movement Skill Assessment [CAMSA], sit and reach, handgrip,
      plank, and body mass index) and children's perceived adequacy and predilection
      toward physical activity as measured by subscales from the Children's Self
      Perceptions of Adequacy in and Predilection for Physical Activity scale (CSAPPA).
      RESULTS: The variable most strongly associated with adequacy and predilection was
      the PACER shuttle run score. The PACER accounted for 10.9% of the variance in
      adequacy and 9.9% of the variance in predilection. Participants' age was
      inversely related to adequacy (beta = - 0.374) and predilection (beta = - 0.621).
      The combination of other variables related to adequacy brought the total variance
      explained to 14.7%, while the model for predilection explained a total of 13.7%.
      CONCLUSIONS: Results indicate an association between cardiorespiratory fitness
      and measures of physical activity adequacy and predilection. These findings
      suggest that practitioners should consider the physiological and psychological
      makeup of the child, and ways to enhance adequacy and predilection among children
      with limited cardiorespiratory fitness, in order to create the best possible
      environment for all children to participate in physical activity.

PMID- 30285678
TI  - N-cadherin in cancer metastasis, its emerging role in haematological malignancies
      and potential as a therapeutic target in cancer.
AB  - In many types of solid tumours, the aberrant expression of the cell adhesion
      molecule N-cadherin is a hallmark of epithelial-to-mesenchymal transition,
      resulting in the acquisition of an aggressive tumour phenotype. This transition
      endows tumour cells with the capacity to escape from the confines of the primary
      tumour and metastasise to secondary sites. In this review, we will discuss how N
      cadherin actively promotes the metastatic behaviour of tumour cells, including
      its involvement in critical signalling pathways which mediate these events. In
      addition, we will explore the emerging role of N-cadherin in haematological
      malignancies, including bone marrow homing and microenvironmental protection to
      anti-cancer agents. Finally, we will discuss the evidence that N-cadherin may be
      a viable therapeutic target to inhibit cancer metastasis and increase tumour cell
      sensitivity to existing anti-cancer therapies.

PMID- 30285682
TI  - Refining the Canadian Assessment of Physical Literacy based on theory and factor
      analyses.
AB  - BACKGROUND: The Canadian Assessment of Physical Literacy (CAPL) is a 25-indicator
      assessment tool comprising four domains of physical literacy: (1) Physical
      Competence, (2) Daily Behaviour, (3) Motivation and Confidence, and (4) Knowledge
      and Understanding. The purpose of this study was to re-examine the factor
      structure of CAPL scores and the relative weight of each domain for an overall
      physical literacy factor. Our goal was to maximize content representation, and
      reduce construct irrelevant variance and participant burden, to inform the
      development of CAPL-2 (a revised, shorter, and theoretically stronger version of
      CAPL). METHODS: Canadian children (n = 10,034; Mage = 10.6, SD = 1.2; 50.1%
      girls) completed CAPL testing at one time point. Confirmatory factor analysis was
      used. RESULTS: Based on weak factor loadings (lambdas < 0.32) and conceptual
      alignment, we removed body mass index, waist circumference, sit-and-reach
      flexibility, and grip strength as indicators of Physical Competence. Based on the
      factor loading (lambda < 0.35) and conceptual alignment, we removed screen time
      as an indicator of Daily Behaviour. To reduce redundancy, we removed children's
      activity compared to other children as an indicator of Motivation and Confidence.
      Based on low factor loadings (lambdas < 0.35) and conceptual alignment, we
      removed knowledge of screen time guidelines, what it means to be healthy, how to
      improve fitness, activity preferences, and physical activity safety gear
      indicators from the Knowledge and Understanding domain. The final refined CAPL
      model was comprised of 14 indicators, and the four-factor correlated model fit
      the data well (r ranged from 0.08 to 0.76), albeit with an unexpected cross
      loading from Daily Behaviour to knowledge of physical activity guidelines (mean-
      and variance-adjusted weighted least square [WLSMV] chi2(70) = 1221.29, p <
      0.001, Comparative Fit Index [CFI] = 0.947, root mean square error of
      approximation [RMSEA] = 0.041[0.039, 0.043]). Finally, our higher-order model
      with Physical Literacy as a factor with indicators of Physical Competence (lambda
      = 0.68), Daily Behaviour (lambda = 0.91), Motivation and Confidence (lambda =
      0.80), and Knowledge and Understanding (lambda = 0.21) fit the data well.
      CONCLUSIONS: The scores from the revised and much shorter 14-indicator model of
      CAPL can be used to assess the four correlated domains of physical literacy
      and/or a higher-order aggregate physical literacy factor. The results of this
      investigation will inform the development of CAPL-2.

PMID- 30285683
TI  - Postoperative function recovery in patients with endoprosthetic knee replacement
      for bone tumour: an observational study.
AB  - BACKGROUND: The objective of this study is to describe the rehabilitative pathway
      of patients undergoing endoprosthetic knee replacement surgery, build reference
      values of the functional results achieved, and identify possible prognostic
      factors. METHODS: Prospective observational study. All patients undergoing
      resection and knee replacement surgery using a modular prosthesis following bone
      tumor resection were consecutively recruited over the last 2 years. The patients
      were followed for a period of 1 year, the result values were collected at 3, 6
      and 12 months. RESULTS: In total, 30 patients were enrolled. The median age was
      19 years with 33% of patients being female. Median values recorded for knee
      flexion, quadriceps strength, Toronto Extremity Salvage Score, Time Up and Go and
      Six Minutes Walking Test showed an improvement of 16, 25, 18, 48 and 38% from 3
      to 12 months, respectively. The level and width of the resection were correlated
      with the mobility of the knee and the strength of the quadriceps. CONCLUSION:
      Patients undergoing knee replacement for bone tumors were able to achieve
      satisfactory functional outcomes from the first postoperative year. A specific
      assessment of outcomes can be conducted to facilitate the management of patient
      expectations. A very wide resection and interventions of the proximal tibia are
      risk factors for a poorer functional outcome.

PMID- 30285684
TI  - Challenges of achieving sustainable community health services for community case
      management of malaria.
AB  - BACKGROUND: Community Case Management of malaria (CCMm) using Community Health
      Workers (CHWs) is an approach to improve access to timely and effective malaria
      case management in malaria endemic countries. So far the programme has been shown
      to be effective in many communities in sub-Saharan Africa. However, questions
      remain on the sustainability of this programme due to the high dropout cases of
      CHWs given their modest remuneration. The aim of the study was to identify
      challenges of achieving sustainable community health services for CCMm. METHODS:
      A community based qualitative study was conducted in five districts in western
      Kenya where CCMm was being undertaken. In-depth interviews and focus group
      discussions were conducted with the CHWs, mothers of children under-five years
      and key informants such as public health officers and clinicians involved in the
      CCMm. The interviews were audio recorded and conducted in English, Swahili and
      the local language. Recorded interviews were transcribed. Analysis was conducted
      using NVivo version 7 software, where transcripts were coded after which themes
      related to the objectives of the study were identified. RESULTS: The community
      members, the CHWs and stakeholders perceived CCMm as an important approach for
      reducing the burden of malaria. Key informants perceived lack of basic supplies
      (RDTs, gloves), drugs, inadequate remuneration of CHWs and lack of basic working
      equipment as challenges for CCM. CHWs highlighted that lack of drugs and basic
      supplies such as gloves at the health facilities, inadequate community
      sensitization by health workers, inadequate stipend to meet basic needs, as
      challenges of achieving sustainable CCMm. Some clinicians perceived that CHWs
      should not be given Artemisinin-based combination therapy (ACT) as part of the
      CCMm since they might misuse them. CONCLUSION: This study shows that for CCMm to
      be sustainable, concerted efforts from stakeholders are needed to boost the
      programme. Commodities needed for implementation of the programme need to be
      readily available and the morale of the CHWs who undertake CCMm needs boosting.

PMID- 30285686
TI  - Alcohol audio-visual content in formula 1 television broadcasting.
AB  - BACKGROUND: Exposure to audio-visual alcohol content in media is associated with
      subsequent alcohol use among young people. In 2016 Heineken launched its global
      Formula One (F1) partnership and had a significant brand presence at a number of
      2017 F1 race events. We have measured the extent to which Heineken and other
      alcohol content appears in a sample of the first 6 races broadcast in the UK
      during the 2017 F1 Championship. METHODS: We used 1-min interval coding to
      quantify alcohol content in all broadcast footage, including advertisement
      breaks. RESULTS: Alcohol content occurred in all of the races shown and in 41% of
      all advertisement breaks in the programming. The most prominent content was
      alcohol branding, occurring in 39% of race footage intervals. Alcohol branding
      consisted mostly of billboard advertisements or branding on the side of cars or
      racing suits with Heineken and Johnnie Walker being most prominent. Alcohol
      branding was shown in race footage from countries where alcohol promotion is
      prohibited. All of the race footage was broadcast on Channel 4 on a Sunday, with
      start times ranging from 12:35 to 18:45. CONCLUSION: Audio-visual alcohol
      content, including branding, was highly prevalent footage of 2017 F1 races
      broadcast during peak viewing times in the UK. This content is likely to be a
      significant driver of alcohol consumption among children and adolescents.

PMID- 30285685
TI  - Cafeteria assessment for elementary schools (CAFES): development, reliability
      testing, and predictive validity analysis.
AB  - BACKGROUND: Strategies to reduce childhood obesity and improve nutrition include
      creating school food environments that promote healthy eating. Despite well
      documented health benefits of fruit and vegetable (FV) consumption, many U.S.
      school-aged children, especially low-income youth, fail to meet national dietary
      guidelines for FV intake. The Cafeteria Assessment for Elementary Schools (CAFES)
      was developed to quantify physical attributes of elementary school cafeteria
      environments associated with students' selection and consumption of FV. CAFES
      procedures require observation of the cafeteria environment where preparation,
      serving, and eating occur; staff interviews; photography; and scoring. METHODS:
      CAFES development included three phases. First, assessment items were identified
      via a literature review, expert panel review, and pilot testing. Second,
      reliability testing included calculating inter-item correlations, internal
      consistency (Kuder-Richardson-21 coefficients), and inter-rater reliability
      (percent agreement) based on data collected from 50 elementary schools in low
      income communities and 3187 National School Lunch Program participants in four
      U.S. states. At least 43% of each participating school's students qualified for
      free- or reduced-price meals. Third, FV servings and consumption data, obtained
      from lunch tray photography, and multi-level modeling were used to assess the
      predictive validity of CAFES. RESULTS: CAFES' 198 items (grouped into 108
      questions) capture four environmental scales: room (50 points), table/display
      (133 points), plate (4 points), and food (11 points). Internal consistency (KR
      21) was 0.88 (overall), 0.80 (room), 0.72 (table), 0.83 (plate), and 0.58 (food).
      Room subscales include ambient environment, appearance, windows,
      layout/visibility, healthy signage, and kitchen/serving area. Table subscales
      include furniture, availability, display layout/presentation, serving method, and
      variety. Inter-rater reliability (percent agreement) of the final CAFES tool was
      90%. Predictive validity analyses indicated that the total CAFES and four
      measurement scale scores were significantly associated with percentage consumed
      of FV served (p < .05). CONCLUSIONS: CAFES offers a practical and low-cost
      measurement tool for school staff, design and public health practitioners, and
      researchers to identify critical areas for intervention; suggest low- and no-cost
      intervention strategies; and contribute to guidelines for cafeteria design, food
      presentation and layout, and operations aimed at promoting healthy eating among
      elementary school students.

PMID- 30285687
TI  - Canadian Assessment of Physical Literacy Second Edition: a streamlined assessment
      of the capacity for physical activity among children 8 to 12 years of age.
AB  - BACKGROUND: The Canadian Assessment of Physical Literacy (CAPL) assesses the
      capacity of children to lead a physically active lifestyle. It is comprised of a
      battery of standardized assessment protocols that reflect the Canadian consensus
      definition of physical literacy. The Royal Bank of Canada Learn to Play -
      Canadian Assessment of Physical Literacy study implemented the CAPL with 10,034
      Canadian children (50.1% female), 8 to 12 years of age. Feedback during data
      collection, necessary changes identified by the coordinating centre, and recent
      data analyses suggested that a streamlined, second edition of the CAPL was
      required. The purpose of this paper is to describe the methods used to develop
      the CAPL second edition (CAPL-2). METHODS: The larger dataset created through the
      RBC-Learn to Play CAPL study enabled the re-examination of the CAPL model through
      factor analyses specific to Canadian children 8 to 12 years of age from across
      Canada. This comprehensive database was also used to examine the CAPL protocols
      for redundancy or variables that did not contribute significantly to the overall
      assessment. Removing redundancy had been identified as a priority in order to
      reduce the high examiner and participant burden. The "lessons learned" from such
      a large national surveillance project were reviewed for additional information
      regarding the changes that would be required to optimize the assessment of
      children's physical literacy. In addition, administrative changes, improvements,
      and corrections were identified as necessary to improve the quality and accuracy
      of the CAPL manual and training materials. RESULTS: For each domain of the CAPL,
      recommended changes based on the factor analyses, qualitative feedback and
      theoretical considerations significantly reduced the number of protocols.
      Specific protocol combinations were then evaluated for model fit within the
      overarching concept of physical literacy. The CAPL-2 continues to reflect the
      four components of the Canadian consensus definition of physical literacy:
      Motivation and Confidence, Physical Competence, Knowledge and Understanding, and
      engagement in Physical Activity Behaviour. The CAPL-2 is comprised of three
      Physical Competence protocols (plank, Progressive Aerobic Cardiovascular
      Endurance Run [PACER], Canadian Agility and Movement Skill Assessment [CAMSA]),
      two Daily Behaviour protocol (pedometer steps, self-reported physical activity),
      and a 22-item questionnaire assessing the physical literacy domains of Motivation
      and Confidence, and Knowledge and Understanding. Detailed information about the
      CAPL-2 is available online ( www.capl-eclp.ca ). CONCLUSIONS: The CAPL-2
      dramatically reduces examiner and participant burden (three Physical Competence
      protocols, two Daily Behaviour protocols, and a 22-response questionnaire; versus
      eight Physical Competence protocols, three Daily Behaviour protocols and a 72
      response questionnaire for the original CAPL), while continuing to be a
      comprehensive assessment of all aspects of children's physical literacy using the
      Canadian consensus definition of this term. Like the original, the CAPL-2
      continues to offer maximum flexibility to practitioners, who can choose to
      complete the entire CAPL-2 assessment, only one or more domains, or select
      individual protocols. Regardless of the assessment selected, scores are available
      to interpret the performance of each child relative to Canadian children of the
      same age and sex. All of the protocols included in the CAPL-2 have published
      reports of validity and reliability for this age group (8 to 12 years). The
      detailed manual for CAPL-2 administration, along with training materials and
      other resources, are available free of charge on the CAPL-2 website ( www.capl
      eclp.ca ). All CAPL-2 materials and resources, including the website, are
      available in both English and French.

PMID- 30285688
TI  - Associations between domains of physical literacy by weight status in 8- to 12
      year-old Canadian children.
AB  - BACKGROUND: The Canadian Assessment of Physical Literacy (CAPL) is divided into
      four domains (Physical Competence, Daily Behaviour, Motivation and Confidence,
      and Knowledge and Understanding) and provides a robust and comprehensive
      assessment of physical literacy. As weight status is known to influence health
      related behaviours such as physical fitness and activity, it is important to
      investigate whether the associations between the domains of physical literacy
      vary among children of different weight status. The aim of this study was to
      determine the associations among the four domains of physical literacy stratified
      by weight status. METHODS: Canadian children aged 8 to 12 years (n = 8343, 63.6%
      healthy-weight) completed the CAPL. Differences in domain scores and overall
      physical literacy score by weight status (children of healthy weight versus
      children with overweight/obese) were assessed using MANOVA (multivariate analysis
      of variance). Partial correlations between the four domains were calculated,
      adjusting for gender and age, and correlation coefficients of both weight status
      groups were compared using the Steiger test. RESULTS: For all four domains as
      well as overall physical literacy, healthy-weight children had higher scores than
      their overweight/obese peers (Cohen's d ranged from 0.05 to 0.44). Weak to
      moderate correlations were found between all of the domains for both groups.
      Correlation coefficients for Physical Competence and Daily Behaviour as well as
      for Physical Competence and Knowledge and Understanding were generally stronger
      in the healthy-weight children (r = 0.29 and 0.22, respectively) compared with
      the overweight/obese children (r = 0.23 and 0.17, respectively). CONCLUSIONS: All
      of the domains of the CAPL correlate positively with each other regardless of
      weight status, with a trend for these correlation coefficients to be slightly
      stronger in the healthy-weight children. The overall weak to moderate
      correlations between the domains in both groups suggest that the CAPL domains are
      not measuring the same constructs, thus providing support for CAPL's psychometric
      architecture in both healthy-weight and overweight/obese children.

PMID- 30285689
TI  - Public awareness and individual responsibility needed for judicious use of
      antibiotics: a qualitative study of public beliefs and perceptions.
AB  - BACKGROUND: High consumption of antibiotics has been identified as an important
      driver for the increasing antibiotic resistance, considered to be one of the
      greatest threats to public health globally. Simply informing the public about
      this consequence is insufficient to induce behavioral change. This study explored
      beliefs and perceptions among Swedes, with the aim of identifying factors
      promoting and hindering a judicious approach to antibiotics use. The study
      focused primarily on the medical use of antibiotics, also considering other
      aspects connected with antibiotic resistance, such as travelling and food
      consumption. METHODS: Data were collected through focus group discussions at the
      end of 2016. Twenty-three Swedes were recruited using an area-based approach and
      purposive sampling, aiming for as heterogeneous groups as possible regarding
      gender (13 women, 10 men), age (range 20-81, mean 38), and education level.
      Interview transcripts were analyzed using qualitative content analysis. The
      Health Belief Model was used as a theoretical framework. RESULTS: Antibiotic
      resistance was identified by participants as a health threat with the potential
      for terrible consequences. The severity of the problem was perceived more
      strongly than the actual likelihood of being affected by it. Metaphors such as
      climate change were abundantly employed to describe antibiotic resistance as a
      slowly emerging problem. There was a tension between individual (egoistic) and
      collective (altruistic) reasons for engaging in judicious behavior. The
      individual effort needed and antibiotics overprescribing were considered major
      barriers to such behavior. In their discussions, participants stressed the need
      for empowerment, achieved through good health communication from authorities and
      family physicians. CONCLUSIONS: Knowledge about antibiotic consumption and
      resistance, as well as values such as altruism and trust in the health care
      system, has significant influence on both perceptions of individual
      responsibility and on behavior. This suggests that these factors should be
      emphasized in health education and health promotion. To instead frame antibiotic
      resistance as a slowly emerging disaster, risks diminish the public perception of
      being susceptible to it.

PMID- 30285690
TI  - Associations between teacher training and measures of physical literacy among
      Canadian 8- to 12-year-old students.
AB  - BACKGROUND: Quality physical education (PE) contributes to the development of
      physical literacy among children, yet little is known about how teacher training
      relates to this development. We assessed the association between teacher
      training, and the likelihood that children met recommended achievement levels for
      components of physical literacy as defined by the Canadian Assessment of Physical
      Literacy (CAPL). METHODS: Canadian children (n = 4189; M = 10.72 years, SD =
      1.19) from six provinces completed the CAPL. Logistic regression was used to
      examine the relationship between teacher training (generalist/PE specialist),
      adjusting for children's age and gender, and physical competence protocols (sit
      and reach, handgrip, plank, Progressive Aerobic Cardiovascular Endurance Run
      [PACER], body mass index [BMI], waist circumference, Canadian Agility and
      Movement Skill Assessment [CAMSA]), the four CAPL domain scores, and the total
      CAPL score. RESULTS: Teacher training, in addition to children's age and gender,
      explained only a very small proportion of variance in each model (all R2 < 0.03).
      Children taught by a generalist were less likely to reach recommended levels of
      motivation and confidence (OR = 0.83, 95% CI, 0.72-0.95) or CAMSA scores (OR =
      0.77, 95% CI, 0.67-0.90), even when accounting for a significant increase in
      CAMSA score with age (OR = 1.18, 95% CI, 1.12-1.26). All other associations
      between measures of components of physical literacy and teacher training were not
      significant. CONCLUSIONS: While teacher training is hypothesized to contribute to
      the development of physical literacy among elementary school students, the
      observed effects in this study were either small or null. Children taught by PE
      specialists were more likely than those taught by generalists to demonstrate
      recommended levels of motivation and confidence, and to have better movement
      skills, which are hypothesized to be critical prerequisites for the development
      of a healthy lifestyle. Further research with more robust designs is merited to
      understand the impact of teachers' training on the various components of physical
      literacy development.

PMID- 30285691
TI  - Lymph node ratio is inferior to pN-stage in predicting outcome in colon cancer
      patients with high numbers of analyzed lymph nodes.
AB  - BACKGROUND: The lymph node ratio (LNR), i.e. the number of positive lymph nodes
      (LN) divided by the total number of analyzed LN, has been described as a strong
      outcome predictor in node-positive colon cancer patients. However, most published
      analyses are constrained by relatively low numbers of analyzed LN. Therefore, the
      objective of the present study was to evaluate the prognostic impact of LNR in
      colon cancer patients with high numbers of analyzed LN. METHODS: One hundred
      sixty-six colon cancer patients underwent open colon resection. All node-positive
      patients were analyzed for this study. The number of analyzed LN, of positive LN,
      the disease-free (DFS) and overall survival (OS) time were prospectively
      recorded. Patients were dichotomously allocated to a high or a low LNR-group,
      respectively, with the median LNR (0.125) as a cut-off value. Median follow-up
      was 34.3 months. RESULTS: Fifty-eight patients (34.9%) were node-positive. The
      median number of analyzed LN was 23 (range 8-54). DFS and OS were significantly
      shorter in pN2 vs pN1 patients (p < 0.001, and p = 0.001, respectively), and in
      LNR high vs low patients (p = 0.032, and p = 0.034, respectively). pN2 (vs pN1)
      disease showed hazard ratios (HR) of 6.2 (p < 0.001), and 6.8 (p < 0.005; for DFS
      and OS, respectively), while LNR high (vs low) showed HR of 3.0 (p =0.041), and
      4.5 (p = 0.054). CONCLUSIONS: LNR is a reasonable outcome predictor in node
      positive colon cancer patients. However, LNR is inferior to pN-stage in
      predicting survival in patients with high number of harvested lymph nodes.

PMID- 30285692
TI  - Infection after knee replacement: a qualitative study of impact of periprosthetic
      knee infection.
AB  - BACKGROUND: Approximately 340,000 knee replacements are performed each year in
      the USA and UK. Around 1% of patients who have had knee replacement develop deep
      infection around the prosthesis: periprosthetic knee infection. Treatment often
      requires a combination of one or more major operations and antibiotic therapy.
      This study aimed to understand and characterise patients' experiences of
      periprosthetic knee infection. METHODS: Qualitative semi-structured interviews
      were conducted with 16 patients (9 men, 7 women; 59-80 years, mean age 72) who
      experienced periprosthetic knee infection and subsequent revision treatment in
      six National Health Service orthopaedic departments. Interviews were audio
      recorded, transcribed, anonymised and analysed thematically. The concept of
      biographical disruption was used to frame our analysis, and four transcripts
      double-coded for rigour. Patients were interviewed between two and 10 months
      after surgical revision. RESULTS: Participant experiences can be characterised
      according to three aspects of biographical disruption which we have used to frame
      our analysis: onset and the problem of recognition; emerging disability and the
      problem of uncertainty, and chronic illness and the mobilisation of resources.
      Participants' experiences of infection and treatment varied, but everyone who
      took part reported that infection and revision treatment had devastating effects
      on them. Participants described use of social and healthcare support and a need
      for more support. Some participants thought that the symptoms that they had first
      presented with had not been taken seriously enough. CONCLUSIONS: Periprosthetic
      knee infection and its treatment can be life-changing for patients, and there is
      a need for greater support throughout treatment and lengthy recovery. Future work
      could look at preparedness for adverse outcomes, help-seeking in impactful
      situations, and information for healthcare professionals about early signs and
      care for periprosthetic infection.

PMID- 30285693
TI  - Physical literacy levels of Canadian children aged 8-12 years: descriptive and
      normative results from the RBC Learn to Play-CAPL project.
AB  - BACKGROUND: The current physical literacy level of Canadian children is unknown.
      The Royal Bank of Canada (RBC) Learn to Play - Canadian Assessment of Physical
      Literacy (CAPL) project, which is anchored in the Canadian consensus statement
      definition of physical literacy, aimed to help establish the current physical
      literacy level of Canadian children. METHODS: The CAPL was used to assess the
      physical literacy (and component domains: Daily Behaviour, Physical Competence,
      Knowledge and Understanding, and Motivation and Confidence) of Canadian children
      aged 8-12 years. Data were collected from 11 sites across Canada, yielding a
      sample of 10,034 participants (5030 girls). Descriptive statistics by age and
      gender were calculated and percentile distributions of physical literacy scores,
      including each domain and individual measure, were derived. RESULTS: The mean age
      of participants was 10.1 +/- 1.2 years. Total physical literacy scores (out of
      100) were on average 63.1 +/- 13.0 for boys and 62.2 +/- 11.3 for girls. For boys
      and girls respectively, domain scores were 19.9 +/- 4.7 and 19.3 +/- 4.1 (out of
      32) for Physical Competence; 18.6 +/- 7.9 and 18.5 +/- 7.4 (out of 32) for Daily
      Behaviour; 12.7 +/- 2.8 and 12.2 +/- 2.6 (out of 18) for Motivation and
      Confidence; and 11.8 +/- 2.8 and 12.2 +/- 2.6 (out of 18) for Knowledge and
      Understanding. Physical Competence measures were on average 28.1 +/- 8.4 cm (sit
      and-reach flexibility), 33.5 +/- 9.4 kg (grip strength, right + left), 23.4 +/-
      14.1 laps (Progressive Aerobic Cardiovascular Endurance Run [PACER] shuttle run),
      61.8 +/- 43.8 s (isometric plank), 19.0 +/- 3.8 kg/m2 (body mass index), 67.3 +/-
      10.8 cm (waist circumference), and 20.6 +/- 3.9 out of 28 points for the Canadian
      Agility and Movement Skill Assessment (CAMSA), with scores for boys higher than
      girls and older children higher than younger children for grip strength, PACER,
      plank, and CAMSA score. Girls and younger children had better scores on the sit
      and-reach flexibility than boys and older children. Daily pedometer step counts
      were higher in boys than girls (12,355 +/- 4252 vs. 10,779 +/- 3624), and
      decreased with age. CONCLUSIONS: These results provide the largest and most
      comprehensive assessment of physical literacy of Canadian children to date,
      providing a "state of the nation" baseline, and can be used to monitor changes
      and inform intervention strategies going forward.

PMID- 30285695
TI  - Oxygen versus air-driven nebulisers for exacerbations of chronic obstructive
      pulmonary disease: a randomised controlled trial.
AB  - BACKGROUND: In exacerbations of chronic obstructive pulmonary disease,
      administration of high concentrations of oxygen may cause hypercapnia and
      increase mortality compared with oxygen titrated, if required, to achieve an
      oxygen saturation of 88-92%. Optimally titrated oxygen regimens require two
      components: titrated supplemental oxygen to achieve the target oxygen saturation
      and, if required, bronchodilators delivered by air-driven nebulisation. The
      effect of repeated air vs oxygen-driven bronchodilator nebulisation in acute
      exacerbations of chronic obstructive pulmonary disease is unknown. We aimed to
      compare the effects of air versus oxygen-driven bronchodilator nebulisation on
      arterial carbon dioxide tension in exacerbations of chronic obstructive pulmonary
      disease. METHODS: A parallel group double-blind randomised controlled trial in 90
      hospital in-patients with an acute exacerbation of COPD. Participants were
      randomised to receive two 2.5 mg salbutamol nebulisers, both driven by air or
      oxygen at 8 L/min, each delivered over 15 min with a 5 min interval in-between.
      The primary outcome measure was the transcutaneous partial pressure of carbon
      dioxide at the end of the second nebulisation (35 min). The primary analysis used
      a mixed linear model with fixed effects of the baseline PtCO2, time, the
      randomised intervention, and a time by intervention interaction term; to estimate
      the difference between randomised treatments at 35 min. Analysis was by intention
      to-treat. RESULTS: Oxygen-driven nebulisation was terminated in one participant
      after 27 min when the PtCO2 rose by > 10 mmHg, a predefined safety criterion. The
      mean (standard deviation) change in PtCO2 at 35 min was 3.4 (1.9) mmHg and 0.1
      (1.4) mmHg in the oxygen and air groups respectively, difference (95% confidence
      interval) 3.3 mmHg (2.7 to 3.9), p < 0.001. The proportion of patients with a
      PtCO2 change >=4 mmHg during the intervention was 18/45 (40%) and 0/44 (0%) for
      oxygen and air groups respectively. CONCLUSIONS: Oxygen-driven nebulisation leads
      to an increase in PtCO2 in exacerbations of COPD. We propose that air-driven
      bronchodilator nebulisation is preferable to oxygen-driven nebulisation in
      exacerbations of COPD. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry number ACTRN12615000389505 . Registration confirmed on 28/4/15.

PMID- 30285696
TI  - Correction to: Number-needed-to-treat analysis of clinical progression in
      patients with metastatic castration-resistant prostate cancer in the STRIVE and
      TERRAIN trials.
AB  - It has been highlighted that in the original article [1] there was a typesetting
      mistake in the Results - NNT in Strive section. This Correction article states
      the incorrect and correct sentence.

PMID- 30285694
TI  - Cardiorespiratory fitness is associated with physical literacy in a large sample
      of Canadian children aged 8 to 12 years.
AB  - BACKGROUND: The associations between cardiorespiratory fitness (CRF) and physical
      literacy in children are largely unknown. The aim of this study was to assess the
      relationships between CRF, measured using the 20-m shuttle run test (20mSRT), and
      components of physical literacy among Canadian children aged 8-12 years. METHODS:
      A total of 9393 (49.9% girls) children, with a mean (SD) age of 10.1 (+/-1.2)
      years, from a cross-sectional surveillance study were included for this analysis.
      The SRT was evaluated using a standardized 15 m or 20 m protocol. All 15 m SRTs
      were converted to 20mSRT values using a standardized formula. The four domains of
      physical literacy (Physical Competence, Daily Behaviour, Motivation and
      Confidence, and Knowledge and Understanding) were measured using the Canadian
      Assessment of Physical Literacy. Tertiles were identified for 20mSRT laps,
      representing low, medium, and high CRF for each age and gender group. Cohen's d
      was used to calculate the effect size between the low and high CRF groups.
      RESULTS: CRF was strongly and favourably associated with all components of
      physical literacy among school-aged Canadian children. The effect size between
      low and high CRF tertile groups was large for the Physical Competence domain
      (Cohen's d range: 1.11-1.94) across age and gender groups, followed by moderate
      to large effect sizes for Motivation and Confidence (Cohen's d range: 0.54-1.18),
      small to moderate effect sizes for Daily Behaviour (Cohen's d range: 0.25-0.81),
      and marginal to moderate effect sizes for Knowledge and Understanding (Cohen's d
      range: 0.08-0.70). CONCLUSIONS: This study identified strong favourable
      associations between CRF and physical literacy and its constituent components in
      children aged 8-12 years. Future research should investigate the sensitivity and
      specificity of the 20mSRT in screening those with low physical literacy levels.

PMID- 30285697
TI  - Nationwide surveillance algorithms for tuberculosis among immigrant workers from
      highly endemic countries following pre-entry screening in Taiwan.
AB  - BACKGROUND: This cross-sectional study was retrospectively performed to assess
      the trend of tuberculosis (TB) among Taiwan's immigrant workers from highly TB
      endemic countries under an intervention of conducting a 4-round follow-up (at 0-3
      days and 6, 18, and 30 months post-migration) screening program with initial
      chest X-ray (CXR) following an overseas, pre-entry normal CXR. METHODS: The
      immigrant workers with TB disease enrolled in the Taiwan TB registry database in
      2011-2014 were analyzed and linked to an immigrant worker physical exam database
      to stratify TB case categories of actively screened or not for comparison.
      RESULTS: Following pre-entry screening for the admission of CXR-normal immigrant
      workers from highly endemic countries, the overall TB incidence of 70.6
      128.6/100,000 person-years resulted either from a subsequent series of 4-round
      post-entry active screenings or misalliance algorithms, including passive
      diagnostics for the illness. Overall, the TB relative risk based on incidence in
      the immigrant working population was 2.2- to 5.5-fold greater than that among
      corresponding age Taiwanese, with 14.3% (15.5/100,000 person-years) sputum-smear
      positive pulmonary TB (SS+ PTB), 74.2% (80.8/100,000 person-years) sputum-smear
      negative (SS-) PTB, and 7.8% (8.5/100,000 person-years) only extra-pulmonary TB
      (EPTB). Regarding the clinical characteristics, 55.5% TB cases - identified
      through passive illness diagnostics vs. 44.5% TB cases actively identified
      through mandatory screenings, were higher in SS+ PTB (adjusted odds Ratio (aOR):
      1.5, 95% CI: 1.1-2.0, P = 0.008), higher in SC+ PTB (aOR: 1.4, 95% CI: 1.1-1.7, P
      = 0.004), higher in concurrent extra-pulmonary TB (aOR: 8.9, CI: 4.5-7.4, P <
      0.001), and higher in normal CXR TB (aOR: > 100, CI: 0- > 100, P = 0.908). The TB
      yields of 3rd- to 4th-round screenings were higher than those of 1st- and 2nd
      round screenings and ranged from 52.6-65.3 cases per 100,000 screenings in 2013
      2014. CONCLUSIONS: The multiple post-entry TB screenings with initial CXR for
      high-risk immigrants could actively reduce TB transmission by finding SS- TB
      cases at early stages. The TB yields at post-entry 3rd- to 4th-round screenings
      might imply a persistent reactivation of latent TB. Adding more sensitive,
      economical screenings and preventive treatments for latent TB infection is a
      comprehensive approach for accelerating TB elimination.

PMID- 30285699
TI  - Factors associated with late presentation of cervical cancer cases at a district
      hospital: a retrospective study.
AB  - BACKGROUND: Cervical cancer is the leading and most common female cancer among
      women in Ghana. Although there are screening methods to detect premalignant
      lesions for treatment, screening coverage in Ghana is 2.8% and late presentation
      of cases complicates treatment efforts. This study examined the sociodemographic,
      clinical and histological characteristics associated with late presentation of
      cervical cancer cases attending Gynecological Oncology care at Catholic Hospital,
      Battor. METHODS: One hundred and fifty-seven medical records of confirmed cases
      of cervical cancer reporting to the Outpatient Obstetrics and Gynecology
      Department between 2012 and 2016 were reviewed. Relevant data were retrieved
      using abstraction forms. Socio demographic variables investigated were level of
      education attained, marital status, National Health Insurance Scheme membership,
      employment status, place of residence and distance from hospital. Clinical
      variables included intermenstrual/postmenopausal bleeding, previous screening
      history, previous smoking history, age at menarche and number of children.
      Histological variables included subtypes of tumour and characteristics of tumour.
      Pearson's chi-square test and logistic regression analysis were used to determine
      correlates of late stage at presentation with cervical cancer. Sensitivity
      analysis was performed to assess the effect of missing data. RESULTS:
      Approximately two-thirds (65.97%) of the cases presented in advanced stages of
      cervical cancer. Level of education, age at menarche and previous screening
      history were included in a regression model and adjusted for age. Age at menarche
      (n = 66) was eliminated from the model after sensitivity analysis. Among the
      remaining variables, only previous screening history was predictive of late stage
      at presentation of cervical cancer cases. Previously unscreened cases of cervical
      cancer were nearly four times more likely to present late, compared to those who
      had been screened previously (OR 3.91; 95% CI 1.43-10.69). No association was
      observed with sociodemographic and histological characteristics. CONCLUSION: Lack
      of previous screening was associated with late presentation of cervical cancer at
      Catholic Hospital, Battor. Efforts to promote early cervical cancer screening
      should be intensified and future studies may explore an association with age at
      menarche.

PMID- 30285700
TI  - CRISPR/Cas9-mediated genome editing induces gene knockdown by altering the pre
      mRNA splicing in mice.
AB  - BACKGROUND: Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR
      associated protein 9 (CRISPR/Cas9) has been wildly used to generate gene knockout
      models through inducing indels causing frame-shift. However, there are few
      studies concerning the post-transcript effects caused by CRISPR-mediated genome
      editing. RESULTS: In the present study, we showed that gene knockdown model also
      could be generated using CRISPR-mediated gene editing by disrupting the boundary
      of exon and intron in mice (C57BL/6 J). CRISPR induced indel at the boundary of
      exon and intron (5' splice site) caused alternative splicing and produced
      multiple different mRNAs, most of these mRNAs introduced premature termination
      codon causing down expression of the gene. CONCLUSIONS: These results showed that
      alternative splicing mutants were able to generate through CRISPR-mediated genome
      editing by deleting the boundary of exon and intron causing disruption of 5'
      splice site. Although alternative splicing was an unexpected outcome, this
      finding could be developed as a technology to generate gene knockdown models or
      to investigate pre-mRNA splicing.

PMID- 30285698
TI  - Identification of key genes involved in the phenotypic alterations of res
      (restored cell structure by salinity) tomato mutant and its recovery induced by
      salt stress through transcriptomic analysis.
AB  - BACKGROUND: The res (restored cell structure by salinity) mutant, recently
      identified as the first tomato mutant accumulating jasmonate in roots under non
      stressful conditions, exhibits a remarkable growth inhibition and morphological
      alterations in roots and leaves, which are suppressed when the mutant plants are
      exposed to salinity. In order to understand the molecular basis of the phenotype
      recovery induced by salt stress in the res mutant, we carried out a comparative
      transcriptomic analysis in roots and leaves of wild-type and res plants in
      absence of stress (control) and when the phenotypic recovery of res mutant began
      to be observed upon salt stress (5 days of 200 mM NaCl). RESULTS: The number of
      differentially expressed genes was three times greater in roots than in leaves of
      res vs WT plants grown in control, and included the down-regulation of growth
      promoting genes and the up-regulation of genes involved in Ca2+ signalling,
      transcription factors and others related to stress responses. However, these
      expression differences were attenuated under salt stress, coinciding with the
      phenotypic normalisation of the mutant. Contrarily to the attenuated response
      observed in roots, an enhanced response was found in leaves under salt stress.
      This included drastic expression changes in several circadian clock genes, such
      as GIGANTEA1, which was down-regulated in res vs WT plants. Moreover, the higher
      photosynthetic efficiency of res leaves under salt stress was accompanied by
      specific salt-upregulation of the genes RUBISCO ACTIVASE1 and ALTERNATIVE
      OXIDASE1A. Very few genes were found to be differentially expressed in both
      tissues (root and leaf) and conditions (control and salt), but this group
      included SlWRKY39 and SlMYB14 transcription factors, as well as genes related to
      protein homeostasis, especially protease inhibitors such as
      METALLOCARBOXYPEPTIDASE INHIBITOR, which also seem to play a role in the
      phenotype recovery and salt tolerance of res mutant. CONCLUSIONS: In summary, in
      this study we have identified genes which seem to have a prominent role in salt
      tolerance. Moreover, we think this work could contribute to future breeding of
      tomato crops with increased stress tolerance.

PMID- 30285701
TI  - Canada's Physical Literacy Consensus Statement: process and outcome.
AB  - BACKGROUND: Healthy movement behaviours of Canadian children and youth have been
      found to be suboptimal; this is associated with declines in physical fitness,
      increases in obesity, and elevated chronic disease risk. Physical literacy is an
      evolving construct representing foundational domains upon which physically active
      lifestyles are based. Many sectors and organizations in Canada are embracing
      physical literacy in their programs, practices, policies, and research; however,
      the use of inconsistent definitions and conceptualizations of physical literacy
      had been identified by stakeholders as hindering promotion and advancement
      efforts. METHODS: With leadership from ParticipACTION, organizations from the
      physical activity, public health, sport, physical education, and recreation
      sectors collaborated to create a physical literacy consensus definition and
      position statement for use by all Canadian organizations and individuals. The
      process involved an environmental scan, survey of related evidence, stakeholder
      consultations, and creation of a Steering Committee. From this background work a
      consensus statement was drafted, shared with stakeholders, revised, and ratified.
      RESULTS: Canada's Physical Literacy Consensus Statement was launched in June 2015
      at the International Physical Literacy Conference in Vancouver, British Columbia.
      To further promote the Consensus Statement, the Sport for Life Society developed
      and simultaneously released the "Vancouver Declaration", which contained
      additional guidance on physical literacy. Both the Consensus Statement and the
      Declaration endorsed the International Physical Literacy Association's definition
      of physical literacy, namely "the motivation, confidence, physical competence,
      knowledge and understanding to value and take responsibility for engagement in
      physical activities for life". CONCLUSIONS: Sector partners hope that the
      Consensus Statement, with its standardized definition, brings greater harmony,
      synergy, and consistency to physical literacy efforts in Canada and
      internationally. Going forward, the impact of this initiative on the sector, and
      the more distal goal of increasing habitual physical activity levels, should be
      assessed.

PMID- 30285702
TI  - A systematic review of compliance with indoor tanning legislation.
AB  - BACKGROUND: Many jurisdictions have enacted indoor tanning legislation in
      response to the health risks of artificial ultraviolet (UV) radiation exposure.
      Key components of these legislations include banning minors' access, requiring
      parental consent or accompaniment, providing protective eyewear, posting health
      warning signs, and communicating important health risk information. However,
      legislation must be complied with to be impactful. Evidence around compliance
      with indoor tanning legislations has not been synthesized and is an important
      step toward determining changes in practice due to legislation. METHODS: A
      systematic review was conducted to obtain peer-reviewed literature about
      compliance with indoor tanning legislation worldwide. Six databases were
      searched, resulting in 12,398 citations. Sixteen studies met the inclusion
      criteria (peer-reviewed scientific studies, published in English, focused
      primarily on compliance with indoor tanning legislations, and focused on
      commercial indoor tanning in indoor tanning facilities). RESULTS: Compliance with
      most aspects of indoor tanning legislation varied widely. There was good
      compliance for provision of protective eyewear (84 to 100%; mean = 92%; SD = 8).
      Compliance with age restrictions ranged from 0 to 100% (mean = 65%; SD = 25),
      while compliance with posting warning labels in the required locations within a
      tanning facility ranged from 8 to 72% (mean = 44%; SD = 27). Variation in
      compliance may be due to true differences, study methodology, or temporal trends.
      CONCLUSIONS: Variability in compliance with indoor tanning legislation, as found
      in this systematic review, indicates the legislations may not be having their
      intended protective effects on the public's health. The reasons for such low and
      varied compliance with certain aspects of legislation, and high compliance with
      other aspects of legislation, deserve further attention in future research to
      inform best practices around ensuring high and consistent compliance with indoor
      tanning legislations worldwide.

PMID- 30285703
TI  - The relationship between sedentary behaviour and physical literacy in Canadian
      children: a cross-sectional analysis from the RBC-CAPL Learn to Play study.
AB  - BACKGROUND: Physical literacy is the foundation of a physically active lifestyle.
      Sedentary behaviour displays deleterious associations with important health
      indicators in children. However, the association between sedentary behaviour and
      physical literacy is unknown. The purpose of this study was to identify the
      aspects of physical literacy that are associated with key modes of sedentary
      behaviour among Canadian children participating in the RBC-CAPL Learn to Play
      study. METHODS: A total of 8,307 children aged 8.0-12.9 years were included in
      the present analysis. Physical literacy was assessed using the Canadian
      Assessment of Physical Literacy, which measures four domains (Physical
      Competence, Daily Behaviour, Motivation and Confidence, Knowledge and
      Understanding). Screen-based sedentary behaviours (TV viewing, computer and video
      game use), non-screen sedentary behaviours (reading, doing homework, sitting and
      talking to friends, drawing, etc.) and total sedentary behaviour were assessed
      via self-report questionnaire. Linear regression models were used to determine
      significant (p<0.05) correlates of each mode of sedentary behaviour. RESULTS: In
      comparison to girls, boys reported more screen time (2.7+/-2.0 vs 2.2+/-1.8
      hours/day, Cohen's d=0.29), and total sedentary behaviour (4.3+/-2.6 vs 3.9+/-2.4
      hours/day, Cohen's d=0.19), but lower non-screen-based sedentary behaviour (1.6+/
      1.3 vs 1.7+/-1.3 hours/day, Cohen's d=0.08) (all p< 0.05). Physical Competence
      (standardized beta's: -0.100 to -0.036, all p<0.05) and Motivation and Confidence
      (standardized beta's: -0.274 to -0.083, all p<0.05) were negatively associated
      with all modes of sedentary behaviour in fully adjusted models. Knowledge and
      Understanding was negatively associated with screen-based modes of sedentary
      behaviour (standardized beta's: -0.039 to -0.032, all p<0.05), and positively
      associated with non-screen sedentary behaviour (standardized beta: 0.098,
      p<0.05). Progressive Aerobic Cardiovascular Endurance Run score and log
      transformed plank score were negatively associated with all screen-based modes of
      sedentary behaviour, while the Canadian Agility and Movement Skill Assessment
      score was negatively associated with all modes of sedentary behaviour other than
      TV viewing (all p<0.05). CONCLUSIONS: These results highlight differences in the
      ways that screen and non-screen sedentary behaviours relate to physical literacy.
      Public health interventions should continue to target screen-based sedentary
      behaviours, given their potentially harmful associations with important aspects
      of physical literacy.

PMID- 30285704
TI  - A Lanosteryl triterpene from Protorhus longifolia augments insulin signaling in
      type 1 diabetic rats.
AB  - BACKGROUND: A substantial literature supports antidiabetic properties of the
      lanosteryl triterpene (methyl-3beta-hydroxylanosta-9,24-dien-21-oate, RA-3)
      isolated from Protorhus longifolia stem bark. However, the molecular mechanism(s)
      associated with the antihyperglycemic properties of the triterpene remained to be
      explored. The current study aimed at investigating the molecular mechanism(s)
      through which RA-3 improves insulin signaling in streptozotocin-induced type 1
      diabetic rats. METHODS: The type 1 diabetic rats were treated daily with a single
      oral dose of RA-3 (100 mg/kg) for 28 days. The rats were then sacrificed, and
      blood, skeletal muscle and pancreases were collected for biochemical, protein
      expression and histological analysis, respectively. RESULTS: Persistently high
      blood glucose levels in the diabetic control rats significantly increased
      expression of IRS-1Ser307 while the expression of p-Akt Ser473, p-GSK-3beta Ser9,
      GLUT 4 and GLUT 2 were decreased. However, enhanced muscle insulin sensitivity,
      which was indicated by a decrease in the expression of IRS-1ser307 with a
      concomitant increase in the p-AktSer473, p-GSK-3beta Ser9, GLUT 4 and GLUT 2
      expression were observed in the diabetic rats treated with RA-3. The triterpene
      treated animals also showed an improved pancreatic beta-cells morphology, along
      with increased C-peptide levels. An increase in the levels of serum antioxidants
      such as catalase, superoxide dismutase, and reduced glutathione was noted in the
      rats treated with the triterpene, while their serum levels of interleukin-6 and
      malondialdehyde were reduced. CONCLUSIONS: It is apparent that RA-3 is able to
      improve the insulin signaling in type 1 diabetic rats. Its beta (beta)-cells
      protecting mechanism could be attributed to its ability to alleviate inflammation
      and oxidative stress in the cells.

PMID- 30285705
TI  - A high burden of asymptomatic genital tract infections undermines the syndromic
      management approach among adolescents and young adults in South Africa:
      implications for HIV prevention efforts.
AB  - BACKGROUND: Youth in southern Africa, particularly adolescent girls and young
      women, are a key population for HIV prevention interventions. Untreated genital
      tract infections (GTIs) increase both HIV transmission and acquisition risks.
      South African GTI treatment guidelines employ syndromic management, which relies
      on individuals to report GTI signs and symptoms. Syndromic management may,
      however, underestimate cases, particularly among youth. We compared genital tract
      infection (GTI) prevalence by symptom-based and laboratory assessment among
      sexually-experienced youth in South Africa, overall and stratified by sex.
      METHODS: Interviewer-administered surveys assessed socio-demographics, behaviors,
      and GTI symptoms among 352 youth (16-24 yrs., HIV-negative or unknown HIV status
      at enrollment) enrolled in community-based cohorts in Durban and Soweto (2014
      2016). Laboratory tests assessed HIV, Chlamydia trachomatis (CT), Neisseria
      gonorrhoeae (NG), Mycoplasma genitalium (MG), Trichomonas vaginalis (TV)
      infections and, among females, bacterial vaginosis (BV) and Candida species.
      Youth with genital ulcers were tested for HSV-2 and syphilis. We assessed
      sensitivity (and specificity) of symptom-based reporting in identifying
      laboratory-confirmed GTIs. RESULTS: At baseline, 16.2% of females (32/198) and <
      1% (1/154) of males reported >=1 GTI symptom. However, laboratory tests
      identified >=1 GTI in 70.2% and 10.4%, respectively. Female CT prevalence was
      18.2%, NG 7.1%, MG 9.6%, TV 8.1%, and 5.1% were newly diagnosed with HIV. BV
      prevalence was 53.0% and candidiasis 9.6%. One female case of herpes was
      identified (0 syphilis). Male CT prevalence was 7.8%, NG 1.3%, MG 3.3%, TV < 1%,
      and 2.0% were newly diagnosed with HIV. Overall, 77.8% of females and 100% of
      males with laboratory-diagnosed GTIs reported no symptoms or were asymptomatic.
      Sensitivity (and specificity) of symptom-based reporting was 14% (97%) among
      females and 0% (99%) among males. CONCLUSION: A high prevalence of asymptomatic
      GTIs and very poor sensitivity of symptom-based reporting undermines the
      applicability of syndromic GTI management, thus compromising GTI control and HIV
      prevention efforts among youth. Syndromic GTI management does not meet the sexual
      health needs of young people. Policy changes incorporating innovations in GTI
      diagnostic testing are needed to reduce GTIs and HIV-associated risks among
      youth.

PMID- 30285707
TI  - The relationship between the abundance of the Nigeria-Cameroon chimpanzee (Pan
      troglodytes ellioti) and its habitat: a conservation concern in Mbam-Djerem
      National Park, Cameroon.
AB  - BACKGROUND: Understanding the relationship between great apes and their habitat
      is essential for the development of successful conservation strategies. The
      chimpanzee Pan troglodytes ellioti is endemic to Nigeria and Cameroon, and
      occupies an ecologically diverse range of habitats from forests to forest
      savannah mosaic in Mbam-Djerem National Park (MDNP) in Cameroon. The habitat
      variation in chimpanzees is poorly understood in MDNP which provides an excellent
      opportunity to assess ecological factors that shape the abundance and
      distribution patterns of P. t. ellioti over a small geographic scale. RESULTS: We
      counted 249 nests along 132 km of transects in total. Of these, 119 nests along
      68 km occurred in dense forest and 130 nests along 64 km in forest-savannah
      mosaic. Chimpanzee density was 0.88 [95% CI (0.55-1.41)] individuals/km2 in the
      dense forest and 0.59 [95% CI (0.19-1.76)] in the forest-savannah mosaic. Nest
      abundance varied with vegetation type and was higher in areas with dense canopy
      cover, steeper slopes and relatively higher altitudes. CONCLUSIONS: Our estimates
      of chimpanzee densities were lower than reported in other studied populations in
      the range of the Nigeria-Cameroon chimpanzee. However, we found that habitat
      features, slope and altitude likely play a role in shaping patterns of chimpanzee
      nesting ecology. Further studies need to be focused on nest decay rates and
      phenology of useful plants in order to model chimpanzee abundance and
      distribution in Mbam-Djerem National Park.

PMID- 30285708
TI  - Bridging the gap to effective feedback in residency training: perceptions of
      trainees and teachers.
AB  - BACKGROUND: Clinical feedback is an important part of residency training, yet
      literature suggests this complex interaction is not completely understood. In
      particular, little is known about what resident versus attending physicians
      expect as feedback. This study investigates this gap in knowledge by examining
      differences in interactions that residents and attendings view as feedback.
      METHODS: Surveys containing sample clinical feedback scenarios were distributed
      to residents and attending physicians in emergency medicine and general surgery
      at a large academic medical center. Respondents were asked to decide whether
      useful feedback was provided in each scenario, and responses were compared
      between the two groups. Continuous features were summarized with medians,
      interquartile ranges (IQRs), and ranges; categorical features were summarized
      with frequency counts and percentages. Comparisons of features between residents
      and attendings were evaluated using Wilcoxon rank sum, chi-square, and Fisher
      exact tests. Statistical analyses were performed using version 9.4 of the SAS
      software package (SAS Institute, Inc.; Cary, NC). All tests were two-sided and p
      values < 0.05 were considered statistically significant. RESULTS: Seventy-two
      individuals responded to the survey out of approximately 110 invitations sent
      (65%), including 35 (49%) residents and 37 (51%) attendings. Of 35 residents, 31
      indicated their level of training, which included 13 (42%) PGY-1, 9 (29%) PGY-2,
      6 (19%) PGY-3, and 3 (10%) PGY-4, respectively. Of 37 attendings, 34 indicated
      the number of years since completion of residency or last fellowship, at a median
      of 9 years (IQR 4-14; range 1-31). No significant difference was found in
      residents' and attendings' perceptions of what constituted feedback in the sample
      scenarios. CONCLUSIONS: While this study did not find a statistical difference in
      perception of feedback between residents and attendings, additional factors
      should be considered when investigating perceived feedback deficiencies. Further
      research is needed to better understand and improve the clinical feedback
      process.

PMID- 30285706
TI  - Factors mediating the impacts of child abuse and intimate partner violence on
      chronic pain: a cross-sectional study.
AB  - BACKGROUND: Most research on the health impacts of intimate partner violence
      (IPV) and child abuse has been conducted in Western countries and may not be
      generalizable to women living in different contexts, such as Saudi Arabia.
      Chronic pain, a disabling health issue associated with experiences of both child
      abuse and IPV among women, negatively impacts women's well-being, quality of
      life, and level of functioning. Yet, the psychosocial mechanisms that explain how
      abuse relates to chronic pain are poorly understood. We developed and tested a
      theoretical model that explains how both IPV and child abuse are related to
      chronic pain. METHODS: We recruited a convenience sample of 299 Saudi women, who
      had experienced IPV in the past 12 months, from nine primary health care centers
      in Saudi Arabia between June and August 2015. Women completed a structured
      interview comprised of self-report measures of IPV, child abuse, PTSD, depressive
      symptoms, chronic pain, and social support. Using Structural equation modeling
      (SEM), we analyzed the proposed model twice with different mental health
      indicators as mediators: PTSD symptoms (Model 1) and depressive symptoms (Model
      2). RESULTS: Both models were found to fit the data, accounting for 31.6% (Model
      1) and 32.4% (Model 2) of the variance in chronic pain severity. In both models,
      mental health problems (PTSD and depressive symptoms) fully mediated the
      relationship between severity of IPV and child abuse and chronic pain severity.
      Perceived family support partially mediated the relationship between abuse
      severity and depressive symptoms. CONCLUSIONS: These results underscore the
      significance of considering lifetime abuse, women's mental health (depressive and
      PTSD symptoms) and their social resources in chronic pain management and
      treatment.

PMID- 30285709
TI  - Study protocol: evaluation of specialized outpatient palliative care in the
      German state of Hesse (ELSAH study) - work package I: assessing the quality of
      care.
AB  - BACKGROUND: In Germany, patients suffering from life-limiting conditions are
      eligible for specialized outpatient palliative care (SOPC). Evaluation of the
      quality of this service lacks currently integration of patient-relevant outcomes.
      There is also no scientific consensus how to prove quality of care in the special
      context of SOPC adequately. Existing quality reports are primarily based on
      descriptive structural data which do not allow for estimation of process quality
      or result quality. The ELSAH study ('Evaluation of Specialized Outpatient
      Palliative Care in the German state of Hesse') aims to choose - or, if necessary,
      to adopt - to evaluate and to implement a suit of measures to assess, evaluate
      and monitor the quality of specialized, home-based palliative care. METHODS: All
      22 SOPC teams providing their services in the state of Hesse, Germany,
      participate in the ELSAH study. The study is divided in two phases: a preparation
      phase and a main study phase. Based on the findings of the preparation phase we
      have chosen a preliminary set of instruments including the Integrated Palliative
      Outcome Scale, Views on Care, Zarit Burden Interview, Phase of Illness, Goal
      Attainment Scaling, Eastern Cooperative Oncology Group Performance Status,
      Consumer Quality Indices Palliative Care and Sense of Security in Care. During
      the main study phase, we will use a mixed-methods approach to evaluate the
      instruments' psychometric properties (reliability, validity, feasibility and
      practicability), to identify barriers, facilitators and limitations of their
      routine use and to explore how their use affects the care within the SOPC
      setting. DISCUSSION: At the end of this study, an outcome- and patient-centered,
      validated measurement approach should be provided, adapted for standardized
      evaluations in SOPC across patient groups, palliative care services and regions
      nationwide. The standardized application of instruments should allow for making
      valid statements and comparisons of health care quality in SOPC based on process-
      and outcome-evaluation rather than relying on structural data only. Moreover, the
      instruments might directly influence the care of patients in palliative
      situations. TRIAL REGISTRATION: German Clinical Trials Register (DRKS-ID:
      DRKS00012421 ).

PMID- 30285711
TI  - Switching from glargine+insulin aspart to glargine+insulin aspart 30 before
      breakfast combined with exercise after dinner and dividing meals for the
      treatment of type 2 diabetes patients with poor glucose control - a prospective
      cohort study.
AB  - BACKGROUND: This study aimed to examine the switch from glargine+once daily
      insulin aspart (1 + 1 regimen) to glargine+insulin aspart 30 before breakfast
      combined with exercise and in patients with type 2 diabetes mellitus (T2DM) with
      poorly controlled blood glucose levels. METHODS: Consecutive patients with poorly
      controlled T2DM (n = 182) were switched from the 1 + 1 regimen to
      glargine+insulin aspart 30 before breakfast in combination with exercise after
      dinner and dividing meals in two (same final calories intake). The insulin doses
      were adjusted according to blood glucose levels within 4 weeks after the switch
      and maintained for 12 weeks. Fasting blood glucose (FBG), 2-hpostprandial glucose
      (2hPG), glycosylated hemoglobin (HbA1c), body mass index (BMI), daily insulin
      dose, and hypoglycemia events were assessed. RESULTS: Sixteen weeks after the
      switch, 2 h PG levels and HbA1c levels (from 8.5 to 7.4%, P = 0.001) were
      improved. The proportions of patients reaching the HbA1c targets of 7.5% were
      improved (from 22.5 to 58.7%, P = 0.001). Among the 182 patients, 24 (13.2%)
      divided one meal into two meals, and 23 (12.6%) divided two meals into four
      meals. Among all patients, 8.5% had to reuse insulin aspart before dinner after
      the study. One patient with diarrhea and poor appetite experienced severe
      hypoglycemia. The rate of hypoglycemia was 3.76 events/patient-year. The daily
      insulin Aspart 30 dose was higher than the original insulin aspart dose (P =
      0.001). CONCLUSIONS: For patients with poorly controlled T2DM under the 1 + 1
      regimen, switching to glargine+insulin aspart 30 before breakfast combined with
      exercise after dinner and dividing meals showed promising benefits.

PMID- 30285710
TI  - In vitro pro-inflammatory enzyme inhibition and anti-oxidant potential of
      selected Sri Lankan medicinal plants.
AB  - BACKGROUND: The extracts of the ten selected Sri Lankan medicinal plants have
      been traditionally used in the treatment of inflammatory mediated diseases. The
      extracts were investigated for anti-inflammatory and anti-oxidant potential in
      vitro to identify bio-active extracts for further chemical characterization.
      METHODS: In vitro anti-inflammatory activities of total ethanol extracts were
      investigated measuring the inhibitory activities of four pro-inflammatory
      enzymes, arachidonate-5- lipoxygenase (A5-LOX), hyaluronidase (HYL), xanthine
      oxidase (XO) and inducible nitric oxide (iNO) synthase. Cytotoxicity of extracts
      were determined by MTT assay. Oxidative burst inhibition (OBI) on human whole
      blood (WB) and isolated polymorphoneutrophils (PMNs) was carried out for a
      selected bio-active extract. Anti- oxidant activities of the extracts were
      determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging,
      ferric reducing antioxidant power (FRAP), ferrous ion chelation (FIC) and oxygen
      radical absorbance capacity (ORAC) assays. Total polyphenol and total Flavonoid
      contents of the extracts were also determined. The most active plant extract was
      analysed using Gas chromatography-Mass spectrometry (GC-MS) and High Performance
      Liquid Chromatography (HPLC). RESULTS: The ethanol bark extract of Flacourtia
      indica showed the highest A5-LOX (IC50: 22.75 +/- 1.94 g/mL), XO (70.46 +/-
      0.18%; 250 MUg/mL) and iNOs inhibitory activities on LPS- activated raw 264.7
      macrophage cells (38.07 +/- 0.93%; 500 MUg/mL) with promising OBI both on WB
      (IC50: 47.64 2.32 MUg/mL) and PMNs (IC50: 5.02 0.38 MUg/mL). The highest HYL
      inhibitory activity was showed by the leaf extracts of Barathranthus nodiflorus
      (42.31 +/- 2.00%; 500 MUg/mL) and Diospyros ebenum (41.60 +/- 1.18%; 500 MUg/mL).
      The bark and leaf extracts of Callophyllum innophyllum (IC50: 6.99 +/- 0.02
      MUg/mL) and Symplocus cochinchinesis (IC50: 9.85 +/- 0.28 MUg/mL) showed
      promising DPPH free radical scavenging activities. The GC-MS analysis of ethanol
      bark extract of F. indica showed the presence of two major bio-active compounds
      linoleic acid ethyl ester and hexadecanoic acid, ethyl ester (> 2% peak area).
      The HPLC analysis showed the presence polyphenolic compounds. CONCLUSION: The
      ethanol bark extract of F. indica can be identified as a potential candidate for
      the development of anti-inflammatory agents, which deserves further
      investigations. The bio-active plant extracts may be effectively used in the
      applications of cosmetic and health care industry.

PMID- 30285712
TI  - Listen to the outpatient: qualitative explanatory study on medical students'
      recognition of outpatients' narratives in combined ambulatory clerkship and peer
      role-play.
AB  - BACKGROUND: Understanding patients' narratives has been associated with methods
      of improving care that go beyond what may be regarded as a "narrow" view of
      scientific medicine. Medical interview training in which medical students develop
      understanding of the importance of patients' narratives is receiving increased
      attention. However, students generally receive education on patients' narratives
      that does not distinguish inpatients and outpatients. No studies exploring the
      characteristics of outpatients' narratives have been reported. We developed an
      educational program combining ambulatory clerkship and peer role-play using
      actual narratives from outpatients that students had encountered during their
      clerkship. These narratives were used as peer role-play scenarios in which the
      students acted as outpatients. This study explored what and how medical students
      learned about the characteristics of outpatients' narratives through this
      original educational program. METHODS: Participants were 70 fifth-year medical
      students from Nagoya University, Japan. We conducted 13 focus groups, based on a
      convenience sample of 11 groups in 2012, one group in 2013, and one group in 2017
      (from 17 clinical groups in each year). Focus group transcripts were analyzed
      using the "Steps for Coding and Theorization" qualitative data analysis method.
      We assessed medical anthropological findings regarding narratives in a conceptual
      framework. RESULTS: Patients' narratives as perceived by medical students were
      divided into four quadrants by two axes: medical versus lived content, and
      objective versus subjective structure. Students recognized that outpatients'
      narratives mainly used a subjective structure, but were mixed and crossed each
      quadrant. This was described as "irreproducibility." Students also recognized
      that narratives of simulated patients and inpatients were mainly limited to a
      medical-lived content with an objective structure. These differences in narrative
      characteristics were recognized through students' previous interactions with
      simulated patients and inpatients. CONCLUSIONS: Despite some limitations, medical
      students learn about patients' narratives in our original educational program in
      a way that would be difficult to achieve through training using simulated
      patients or inpatients.

PMID- 30285713
TI  - A comprehensive study of the potential phytomedicinal use and toxicity of
      invasive Tithonia species in South Africa.
AB  - BACKGROUND: Tithonia diversifolia and T. rotundifolia belong to the Asteraceae
      family and are native to Mexico and Central America. These plants have become
      invasive in parts of tropical Africa and Asia where they have become an
      ecological, agricultural and economic burden. Tithonia diversifolia is exploited
      by locals in its native and most parts of its invasive range as a source of
      medicines; however, T. rotundifolia is only used for medicinal purposes in one
      country in the native range (Venezuela) and none in the invasive range. Although
      T. diversifolia has been studied for different biological activities, little or
      no attention has been given to T. rotundifolia. This study compared the
      antimicrobial activity, phytochemistry, identification of bioactive compound(s)
      and toxicity levels of different leaf extracts and fractions of T. diversifolia
      and T. rotundifolia. METHODS: Antimicrobial activity was evaluated against seven
      pathogenic bacteria, four non-pathogenic Mycobacterium species and three fungal
      species using serial microdilution assays. Phytochemical contents were determined
      through standard methods of analysis. UPLC/MS was used to analyse the fractions
      to identify possible bioactive compounds that may be responsible for bioactivity,
      while toxicity tests were carried out using the colorimetric MTT assay and the
      Ames test. RESULTS: Both species had a range of antimicrobial activity against
      bacterial, mycobacterial and fungal species. However, T. rotundifolia displayed
      better activity against most of the strains tested with minimum inhibitory
      concentration values ranging between 0.01 and 0.07 mg/ml. Both species were rich
      in phenolics, flavonoids and tannins. Tagitinin A was identified as the main
      compound present in both species, and this compound may be responsible for the
      antimicrobial activity displayed. Toxicity tests showed that T. diversifolia was
      cytotoxic at concentrations used in this study, while T. rotundifolia was not.
      Both species did not show any mutagenic/genotoxic effects. CONCLUSION: The above
      results suggest that both species may be further developed as a source of
      antimicrobials for the treatment of infections caused by opportunistic pathogens.
      They may also serve as alternatives to highly exploited plant species with the
      same medicinal properties. However, T. diversifolia should be used with caution
      as it may be toxic.

PMID- 30285715
TI  - Effect of an audience on trainee stress and performance during simulated neonatal
      intubation: a randomized crossover trial.
AB  - BACKGROUND: Neonatal intubation is a stressful procedure taught to trainees. This
      procedure can attract additional observers. The impact of observers on neonatal
      intubation performance by trainees has not been studied. Our objective was to
      evaluate if additional observers present during neonatal mannequin endotracheal
      intubation (NMEI) by junior trainees, affects their performance and their stress
      levels. METHODS: A randomized cross over trial was conducted. First year
      residents with no experience in neonatal intubation were assigned to NMEI
      condition A or B randomly on day 1. Subjects were crossed over to the other
      condition on day 2. Condition A: Only one audience member was present Condition
      B: Presence of an audience of 5 health care providers. Differences in the time to
      successful NMEI was recorded and compared between conditions. A portable heart
      rate monitor was used to measure peak heart rate above baseline during NMEI under
      both conditions. RESULTS: Forty nine residents were recruited. 72% were female
      with a median age of 25 years (IQR: 24-27). Time to successful intubation was
      comparable under both conditions with a mean difference of - 3.94 s (95% CI: 
      8.2,0.4). Peak heart rate was significantly lower under condition A (mean
      difference - 11.9 beats/min, 95% CI -15.98 to - 7.78). CONCLUSION: Although the
      time required to NMEI did not increase, our results suggest that presence of
      observers significantly increases trainee stress. The addition of extraneous
      observers during simulation training may better equip residents to deal with such
      stressors. TRIAL REGISTRATION: Date of registration: March 2016, NCT 02726724 .

PMID- 30285714
TI  - Protective effects and mechanisms of Terminalia catappa L. methenolic extract on
      hydrogen-peroxide-induced oxidative stress in human skin fibroblasts.
AB  - BACKGROUND: Oxidative stress plays a crucial role in aging-related phenomenon,
      including skin aging and photoaging. This study investigated the protective role
      and possible mechanism of Terminalia catappa L. methanolic extract (TCE) in human
      fibroblasts (Hs68) against hydrogen peroxide (H2O2)-induced oxidative damage.
      METHODS: Various in vitro antioxidant assays were performed in this study. The
      effect and mechanisms of TCE on oxidative stress-induced oxidative damage were
      studied by using western blotting. RESULTS: The IC50 of TCE was 8.2 MUg/mL for
      1,1-diphenyl-2-picrylhydrazyl radical scavenging, 20.7 MUg/mL for superoxide
      anion radical scavenging, 173.0 MUg/mL for H2O2 scavenging, 44.8 MUg/mL for
      hydroxyl radical scavenging, and 427.6 MUg/mL for ferrous chelation activities.
      Moreover, TCE inhibited the H2O2-induced mitogen-activated protein kinase
      signaling pathway, resulting in the inhibition of c-Jun, c-Fos, matrix
      metalloproteinase (MMP)-1, MMP-3, MMP-9, and cyclooxygenase-2 expression. TCE
      also increased hemeoxygenase-1 expression inhibited by H2O2. Finally, TCE was
      demonstrated reverse type I procollagen expression in fibroblasts after H2O2
      treatment. CONCLUSIONS: According to our findings, TCE is a potent antioxidant
      and protective agent that can be used in antioxidative stress-induced skin aging.

PMID- 30285716
TI  - The associations between staffing hours and quality of care indicators in long
      term care.
AB  - BACKGROUND: Long-term care (LTC) staffing practices are poorly understood as is
      their influence on quality of care. We examined the relationship between staffing
      characteristics and residents' quality of care indicators at the unit level in
      LTC homes. METHODS: This cross-sectional study collected data from administrative
      records and resident assessments from July 2014 to June 2015 at 11 LTC homes in
      Ontario, Canada comprising of 55 units and 32 residents in each unit. The sample
      included 69 registered nurses, 183 licensed/registered practical nurses, 858
      nursing assistants, and 2173 residents. Practice sensitive, risk-adjusted quality
      indicators were described individually, then combined to create a quality of care
      composite ranking per unit. A multilevel regression model was used to estimate
      the association between staffing characteristics and quality of care composite
      ranking scores. RESULTS: Nursing assistants provided the majority of direct care
      hours in LTC homes (76.5%). The delivery of nursing assistant care hours per
      resident per day was significantly associated with higher quality of resident
      care (p = < 0.01). There were small but significant associations with quality of
      care for nursing assistants with seven or more years of experience (p = 0.02),
      nursing assistants late to shift (p = < 0.01) and licensed/registered practical
      nurses late to shift (p = 0.02). CONCLUSIONS: The number of care hours per
      resident per day delivered by NAs is an important contributor to residents'
      quality of care in LTC homes. These findings can inform hiring and retention
      strategies for NAs in LTC, as well as examine opportunities to optimize the NA
      role in these settings.

PMID- 30285717
TI  - Quantifying suitable late summer brood habitats for willow ptarmigan in Norway.
AB  - BACKGROUND: Habitat models provide information about which habitat management
      should target to avoid species extinctions or range contractions. The willow
      ptarmigan inhabits alpine- and arctic tundra habitats in the northern hemisphere
      and is listed as near threatened (NT) in the Norwegian red list due to declining
      population size. Habitat alteration is one of several factors affecting willow
      ptarmigan populations, but there is a lack of studies quantifying and describing
      habitat selection in willow ptarmigan. We used data from an extensive line
      transect survey program from 2014 to 2017 to develop resource selection functions
      (RSF) for willow ptarmigan in Norway. The selection coefficients for the RSF were
      estimated using a mixed-effects logistic regression model fitted with random
      intercepts for each area. We predicted relative probability of selection across
      Norway and quantile-binned the predictions in 10 RSF bins ranging from low-(1) to
      high-(10) relative probability of selection. RESULTS: Random cross-validation
      suggest that our models were highly predictive, but validation based spatial
      blocking revealed that the predictability was better in southern parts of Norway
      compared to the northernmost region. Willow ptarmigan selected for herb-rich
      meadows and avoided lichen rich heathlands. There was generally stronger
      selection for vegetation types with dense field layer and for rich bogs and
      avoidance of vegetation types with sparse field layer cover and for lowland
      forest. Further, willow ptarmigan selected for areas around the timberline and
      for intermediate slopes. Mapping of the RSF showed that 60% of Norway is in the
      lowest ranked RSF bin and only 2% in the highest ranked RSF bin. CONCLUSIONS:
      Willow ptarmigan selected for vegetation types with dense field layer and bogs at
      intermediate slopes around the timberline. Selection coincides with previous
      habitat selection studies on willow ptarmigan. This is the first attempt to
      assess and quantify habitat selection for willow ptarmigan at a large scale using
      data from line transect distance sampling surveys. Spatial variation in
      predictability suggests that habitat selection in late summer might vary from
      north to south. The resource selection map can be a useful tool when planning
      harvest quotas and habitat interventions in alpine areas.

PMID- 30285718
TI  - Enhancing implementation of measurement-based mental health care in primary care:
      a mixed-methods randomized effectiveness evaluation of implementation
      facilitation.
AB  - BACKGROUND: Mental health care lags behind other forms of medical care in its
      reliance on subjective clinician assessment. Although routine use of standardized
      patient-reported outcome measures, measurement-based care (MBC), can improve
      patient outcomes and engagement, clinician efficiency, and, collaboration across
      care team members, full implementation of this complex practice change can be
      challenging. This study seeks to understand whether and how an intensive
      facilitation strategy can be effective in supporting the implementation of MBC.
      Implementation researchers partnering with US Department of Veterans Affairs (VA)
      leaders are conducting the study within the context of a national initiative to
      support MBC implementation throughout VA mental health services. This study will
      focus specifically on VA Primary Care-Mental Health Integration (PCMHI) programs.
      METHODS: A mixed-methods, multiple case study design will include 12 PCMHI sites
      recruited from the 23 PCMHI programs that volunteered to participate in the VA
      national initiative. Guided by a study partnership panel, sites are clustered
      into similar groups using administrative metrics. Site pairs are recruited from
      within these groups. Within pairs, sites are randomized to the implementation
      facilitation strategy (external facilitation plus QI team) or standard VA
      national support. The implementation strategy provides an external facilitator
      and MBC experts who work with intervention sites to form a QI team, develop an
      implementation plan, and, identify and overcome barriers to implementation. The
      RE-AIM framework guides the evaluation of the implementation facilitation
      strategy which will utilize data from administrative, medical record, and primary
      qualitative and quantitative sources. Guided by the iPARIHS framework and using a
      mixed methods approach, we will also examine factors associated with
      implementation success. Finally, we will explore whether implementation of MBC
      increases primary care team communication and function related to the care of
      mental health conditions. DISCUSSION: MBC has significant potential to improve
      mental health care but it represents a major change in practice. Understanding
      factors that can support MBC implementation is essential to attaining its
      potential benefits and spreading these benefits across the health care system.

PMID- 30285719
TI  - Purchasers' deliberations on psychosocial needs within the process of allocating
      healthcare services for older home-dwelling persons with dementia: a qualitative
      study.
AB  - BACKGROUND: Meeting psychosocial needs is a significant component of quality
      dementia care. To enable persons with dementia to live at home for as long as
      possible, a community healthcare service offering care where physical, social,
      psychological, cultural and spiritual needs are met, is recommended. A
      comprehensive allocation process is required to allocate individually tailored
      healthcare services. However, the allocation process for older home-dwelling
      persons with dementia, specifically for services to safeguard psychosocial needs,
      remains largely unexplored. Accordingly, this study aims to explore purchasers'
      deliberations on psychosocial needs during the process of allocating healthcare
      services to older home-dwelling persons with dementia. METHODS: The study had a
      descriptive design with a qualitative approach. The primary data source was focus
      group interviews with purchasers who assess and allocate healthcare services. The
      interview data were supplemented by a review of administrative decisions made by
      the purchasers. Data from the focus group interviews were analysed using a
      descriptive and interpretive approach. Content analysis of the administrative
      decisions was conducted. RESULTS: The purchasers described the allocation process
      as challenging. The following four themes reflect the complexity of the
      allocation process: (i) an unfamiliar and unclear concept; (ii) a hierarchy of
      needs; (iii) an adjusting allocation process; (iv) a challenging documentation of
      administrative decisions. CONCLUSIONS: The purchasers viewed a comprehensive
      allocation process as important. However, a web of different interplaying aspects
      prevented the purchasers from conducting a comprehensive need-led allocation
      process. Insufficient assessment or allocation threatens the adequate
      safeguarding of the psychosocial needs of persons with dementia. Having varied
      and sufficient services to allocate is of great importance, but is not
      sufficient. Psychosocial needs must be better incorporated as a significant
      element throughout the entire allocation process.

PMID- 30285720
TI  - Novel mutations in TPM2 and PIEZO2 are responsible for distal arthrogryposis (DA)
      2B and mild DA in two Chinese families.
AB  - BACKGROUND: Distal arthrogryposis (DA) is a group of clinically and genetically
      heterogeneous disorders that involve multiple congenital limb contractures and
      comprise at least 10 clinical subtypes. Here, we describe our findings in two
      Chinese families: Family 1 with DA2B (MIM 601680) and Family 2 with mild DA.
      METHODS: To map the disease locus, two-point linkage analysis was performed with
      microsatellite markers closed to TPM2, TNNI2/TNNT3 and TNNC2. In Family 1, a
      positive LOD (logarithm of odds) score was only obtained at the microsatellite
      marker close to TPM2 and mutation screening was performed using direct sequencing
      of TPM2 in the proband. In Family 2, for the LOD score that did not favor linkage
      to any markers, whole-exome sequencing (WES) was performed on the proband. PCR
      restriction fragment length polymorphism (RFLP) and bioinformatics analysis were
      then applied to identify the pathogenic mutations in two families. In order to
      correlate genotype with phenotype in DA, retrospective analyses of phenotypic
      features according to the TPM2 and PIEZO2 mutation spectrums were carried out.
      RESULTS: A heterozygous missense mutation c.308A > G (p.Q103R) in TPM2 in Family
      1, and a novel variation c.8153G > A (p.R2718Q) in PIEZO2 in Family 2 were
      identified. Each of the two novel variants was co-segregated with the DA
      manifestations in the corresponding family. Bioinformatics analysis from several
      tools supported the pathogenicity of the mutations. Furthermore, our study
      suggests that there is no relation between the types or locations of TPM2
      mutations and the clinical characteristics, and that different inheritance modes
      and mutation types concerning PIEZO2 cause distinct clinical manifestations.
      CONCLUSIONS: We report two novel mutations within TPM2 and PIEZO2 responsible for
      DA2B and mild DA in two Chinese families, respectively. Our study expands the
      spectrum of causal mutations in the TPM2 and PIEZO2 genes.

PMID- 30285721
TI  - Evaluation of the relationship between maxillary posterior teeth and the
      maxillary sinus floor using cone-beam computed tomography.
AB  - BACKGROUND: Maxillary posterior teeth have close anatomical proximity to the
      maxillary sinus floor (MSF), and the race, gender, age, side and presence/absence
      of adjacent teeth may influence the mean distances between the root apices and
      the MSF. This study aimed to evaluate both the relationship between the maxillary
      posterior teeth and MSF, and the influence of adjacent teeth loss on the distance
      between the maxillary posterior roots and MSF. METHODS: Cone-beam computed
      tomography images were collected from 1011 Chinese patients. The relationship
      between the maxillary posterior teeth and the MSF was divided into three types:
      Type OS (the root apex extending below/outside the MSF), Type CO (the root apex
      contacting with the MSF), Type IS (the root apex extending above/inside the MSF).
      The minimum vertical distances between the maxillary posterior roots apices and
      the MSF were recorded. The correlations of the distances with gender and age were
      analyzed. The distances between the maxillary posterior root apices and the MSF
      with different types of adjacent teeth loss was evaluated. RESULTS: Type OS was
      the most common relationship of all posterior root apices (P<0.05). Type IS was
      highest in the palatal roots (PRs) of the maxillary first molars (MFMs) and the
      mesiobuccal roots (MBRs) of the maxillary second molars (MSMs) (24.8% and 21.6%)
      (P<0.05). The frequency of Type IS decreased with age except the premolar roots
      and PRs of the MSMs (P<0.05). The MBRs of the MSMs had the lowest distances to
      the MSF (0.8 +/- 2.5 mm), followed by the distobuccal roots of the MSMs (1.3 +/-
      2.7 mm) and the PRs of the MFMs (1.4 +/- 3.4 mm) (P<0.05). Age was an important
      influencing factor to the mean distances while gender had little effects. The
      distance between the maxillary second premolar root apices and the MSF decreased
      with the absence of adjacent teeth (P<0.05). CONCLUSIONS: The maxillary molars
      showed greater proximity to the MSF than premolars. Age had significant impacts
      on the relationship between maxillary posterior roots and MSF. The absence of
      maxillary first molars will influence the proximity of maxillary second premolar
      root apices to MSF.

PMID- 30285722
TI  - Inhibition of RANKL-stimulated osteoclast differentiation by Schisandra chinensis
      through down-regulation of NFATc1 and c-fos expression.
AB  - BACKGROUND: Schisandra chinenesis (SC) has been reported to have ameliorative
      effect on osteoporosis. However, the mechanisms underlying the anti-osteoporosis
      activity of SC have not been clearly elucidated. In the present study, we
      determined the effects of SC on The receptor activator of NF-kB ligand (RANKL)
      induced osteoclastogenesis and its potential mechanism. METHODS: Raw 264.7 cells
      were treated with 0.6, 6 and 60 MUg/mL SC in the presence of 100 ng/mL RANKL for
      7 days. RANKL-induced osteoclast formation was analyzed by tartrate resistant
      acid phosphatase (TRAP) staining. The osteoclast differentiation-related factors
      were confirmed along with TNF-alpha. RESULTS: SC inhibits the RANKL-induced
      osteoclast differentiation in dose-dependent manner within non-toxic
      concentrations. The supernatant concentrations of TNF-alpha were significantly
      decreased by SC treatment. In addition, osteoclastogenesis-related factors, TRAP6
      and NF-kappaB, were markedly decreased by SC in RANKL-induced osteoclasts.
      Mechanistically, SC reduced the RANKL-triggered NFATc1 and c-fos expressions.
      CONCLUSIONS: Taken together, our data suggest that SC can modulate bone
      metabolism by suppressing RANKL-induced osteoclast differentiation.

PMID- 30285723
TI  - Antidiabetic activity, glucose uptake stimulation and alpha-glucosidase
      inhibitory effect of Chrysophyllum cainito L. stem bark extract.
AB  - BACKGROUND: Chrysophyllum cainito L., a tropical fruit tree, has been used as an
      alternative medicine for the treatment of diabetic patients in many countries.
      However, there is very limited scientific rationale for this medical use. The
      present study aimed to evaluate the antidiabetic activity of the extract from C.
      cainito stem bark and the possible mechanisms underlying this activity. METHODS:
      Phytochemistry and in vitro antioxidant capacity of the extract were studied.
      Hypoglycemic activity of the extract was examined in normal and alloxan-induced
      diabetic mice. The effect of C. cainito extract on glucose absorption and glucose
      uptake were conducted using mouse isolated jejunum and abdominal muscle,
      respectively. Finally, an in vitro effect of C. cainito extract on alpha
      glucosidase activity was evaluated. RESULTS: C. cainito extract possessed a
      strong antioxidant activity comparable to the ascorbic acid and butylated
      hydroxytoluene. The extract at 500 mg/kg significantly reduced the area under
      curve of blood glucose level in oral glucose tolerance test in normal mice. In
      alloxan-induced diabetic model, similar to glibenclamide, a single dose of the
      extract significantly decreased fasting blood glucose level from 387.17 +/- 29.84
      mg/dl to 125.67 +/- 62.09 mg/dl after 6 h of administration. From the isolated
      jejunum experiment, the extract at any doses used did not inhibit glucose
      absorption. However, the extract at 50 MUg/ml significantly increased the amount
      of glucose uptake by abdominal muscles in the presence of insulin (P < 0.05).
      Lastly, it was found that the extract produced stronger inhibition of alpha
      glucosidase activity (IC50 = 1.20 +/- 0.09 MUg/ml) than acarbose (IC50 = 198.17
      +/- 4.74 MUg/ml). CONCLUSION: Direct evidence of antidiabetic activity of C.
      cainito stem bark with possible modes of action, glucose uptake stimulation and
      alpha-glucosidase inhibitory effect, was reported for the first time herein.
      These data support the potential use of this plant for the treatment of diabetic
      patients.

PMID- 30285724
TI  - A training programme facilitating guideline use of occupational health
      professionals: a feasibility study.
AB  - BACKGROUND: To evaluate whether a training programme is a feasible approach to
      facilitate occupational health professionals' (OHPs) use of knowledge and skills
      provided by a guideline. METHODS: Feasibility was evaluated by researching three
      aspects: 'acceptability', 'implementation' and 'limited efficacy'. Statements on
      acceptability and implementation were rated by OHPs on 10-point visual analogue
      scales after following the training programme (T2). Answers were analysed using
      descriptive statistics. Barriers to and facilitators of implementation were
      explored through open-ended questions at T2, which were qualitatively analysed.
      Limited efficacy was evaluated by measuring the level of knowledge and skills at
      baseline (T0), after reading the guideline (T1) and directly after completing the
      training programme (T2). Increase in knowledge and skills was analysed using a
      non-paramatric Friedman test and post-hoc Wilcoxon signed rank tests (two
      tailed). RESULTS: The 38 OHPs found the training programme acceptable, judging
      that it was relevant (M: 8, SD: 1), increased their capability (M: 7, SD: 1),
      adhered to their daily practice (M: 8, SD: 1) and enhanced their guidance and
      assessment of people with a chronic disease (M: 8, SD: 1). OHPs found that it was
      feasible to implement the programme on a larger scale (M: 7, SD: 1) but foresaw
      barriers such as 'time', 'money' and organizational constraints. The reported
      facilitators were primarily related to the added value of the knowledge and
      skills to the OHPs' guidance and assessment, and that the programme taught them
      to apply the evidence in practice. Regarding limited efficacy, a significant
      increase was seen in OHPs' knowledge and skills over time (X2 (2) = 53.656, p <
      0.001), with the median score improving from 6.3 (T0), 8.3 (T1) and 12.3 (T2).
      Post-hoc tests indicated a significant improvement between T0 and T1 (p < 0.001)
      and between T1 and T2 (p < 0.001). CONCLUSIONS: The training programme was found
      to be a feasible approach to facilitate OHPs' use of knowledge and skills
      provided by the guideline, from the perspective of OHPs generally (acceptability
      and implementation) and with respect to their increase in knowledge and skills in
      particular (limited efficacy).

PMID- 30285725
TI  - Feasibility, acceptability and potential sustainability of a 'diagonal' approach
      to health services for female sex workers in Mozambique.
AB  - BACKGROUND: Female sex workers (FSWs) in many settings have restricted access to
      sexual and reproductive health (SRH) services. We therefore conducted an
      implementation study to test a 'diagonal' intervention which combined
      strengthening of FSW-targeted services (vertical) with making public health
      facilities more FSW-friendly (horizontal). We piloted it over 18 months and then
      assessed its performance. METHODS: Applying a convergent parallel mixed-methods
      design, we triangulated the results of the analysis of process indicators, semi
      structured interviews with policy makers and health managers, structured
      interviews with health care providers and group discussions with peer outreach
      workers. We then formulated integrated conclusions on the interventions'
      feasibility, acceptability by providers, managers and policy makers, and
      potential sustainability. RESULTS: The intervention, as designed, was considered
      theoretically feasible by all informants, but in practice the expansion of some
      of the targeted services was hampered by insufficient financial resources,
      institutional capacity and buy-in from local government and private partners, and
      could not be fully actualised. In terms of acceptability, there was broad
      consensus on the need to ensure FSWs have access to SRH services, but not on how
      this might be achieved. Targeted clinical services were no longer endorsed by
      national government, which now prefers a strategy of making public services more
      friendly for key populations. Stakeholders judged that the piloted model was not
      fully sustainable, nor replicable elsewhere in the country, given its dependency
      on short-term project-based funding, lack of government endorsement for targeted
      clinical services, and viewing the provision of community activities as a
      responsibility of civil society. CONCLUSIONS: In the current Mozambican context,
      a 'diagonal' approach to ensure adequate access to sexual and reproductive health
      care for female sex workers is not fully feasible, acceptable or sustainable,
      because of insufficient resources and lack of endorsement by national policy
      makers for the targeted, vertical component.

PMID- 30285726
TI  - Cellular network modeling and single cell gene expression analysis reveals novel
      hepatic stellate cell phenotypes controlling liver regeneration dynamics.
AB  - BACKGROUND: Recent results from single cell gene and protein regulation studies
      are starting to uncover the previously underappreciated fact that individual
      cells within a population exhibit high variability in the expression of mRNA and
      proteins (i.e., molecular variability). By combining cellular network modeling,
      and high-throughput gene expression measurements in single cells, we seek to
      reconcile the high molecular variability in single cells with the relatively low
      variability in tissue-scale gene and protein expression and the highly
      coordinated functional responses of tissues to physiological challenges. In this
      study, we focus on relating the dynamic changes in distributions of hepatic
      stellate cell (HSC) functional phenotypes to the tightly regulated physiological
      response of liver regeneration. RESULTS: We develop a mathematical model
      describing contributions of HSC functional phenotype populations to liver
      regeneration and test model predictions through isolation and transcriptional
      characterization of single HSCs. We identify and characterize four HSC
      transcriptional states contributing to liver regeneration, two of which are
      described for the first time in this work. We show that HSC state populations
      change in vivo in response to acute challenges (in this case, 70% partial
      hepatectomy) and chronic challenges (chronic ethanol consumption). Our results
      indicate that HSCs influence the dynamics of liver regeneration through steady
      state tissue preconditioning prior to an acute insult and through dynamic control
      of cell state balances. Furthermore, our modeling approach provides a framework
      to understand how balances among cell states influence tissue dynamics.
      CONCLUSIONS: Taken together, our combined modeling and experimental studies
      reveal novel HSC transcriptional states and indicate that baseline differences in
      HSC phenotypes as well as a dynamic balance of transitions between these
      phenotypes control liver regeneration responses.

PMID- 30285727
TI  - Tinospora cordifolia as a potential neuroregenerative candidate against glutamate
      induced excitotoxicity: an in vitro perspective.
AB  - BACKGROUND: Glutamate, the major excitatory neurotransmitter of CNS acts as a
      neurotoxin at higher concentrations. Prolonged activation of glutamate receptors
      results in progressive neuronal damage by aggravating calcium influx, inducing
      mitochondrial damage and oxidative stress. Excitotoxic cell death is associated
      with the pathogenesis of various neurodegenerative disorders such as trauma,
      brain injury and neurodegenerative diseases. The current study was designed to
      investigate the neuroprotective and neuroregenerative potential of Tinospora
      cordifolia against glutamate-induced excitotoxicity using primary cerebellar
      neuronal cultures as a model system. METHODS: Monosodium salt of glutamate was
      used to induce neurotoxic injury in primary cerebellar neurons. Four extracts
      including Hexane extract, Chloroform extract, Ethyl acetate, and Butanol extract
      were obtained from fractionation of previously reported aqueous ethanolic extract
      of T. cordifolia and tested for neuroprotective activity. Out of the four
      fractions, Butanol extract of T. cordifolia (B-TCE) exhibited neuroprotective
      potential by preventing degeneration of neurons induced by glutamate. Expression
      of different neuronal, apoptotic, inflammatory, cell cycle regulatory and
      plasticity markers was studied by immunostaining and Western blotting. Neurite
      outgrowth and migration were also studied using primary explant cultures, wound
      scratch and gelatin zymogram assay. RESULTS: At molecular level, B-TCE
      pretreatment of glutamate-treated cultures normalized the stress-induced
      downregulation in the expression of neuronal markers (MAP-2, GAP-43, NF200) and
      anti-apoptotic marker (Bcl-xL). Further, cells exposed to glutamate showed
      enhanced expression of inflammatory (NF-kappaB, AP-1) and senescence markers
      (HSP70, Mortalin) as well as the extent of mitochondrial damage. However, B-TCE
      pretreatment prevented this increase and inhibited glutamate-induced onset of
      inflammation, stress and mitochondrial membrane damage. Furthermore, B-TCE was
      observed to promote regeneration, migration and plasticity of cerebellar neurons,
      which was otherwise significantly inhibited by glutamate treatment. CONCLUSION:
      These results suggest that B-TCE may have neuroprotective and neuroregenerative
      potential against catastrophic consequences of glutamate-mediated excitotoxicity
      and could be a potential therapeutic candidate for neurodegenerative diseases.

PMID- 30285729
TI  - Assessment of research waste part 2: wrong study populations- an exemplar of
      baseline vitamin D status of participants in trials of vitamin D supplementation.
AB  - BACKGROUND: Research waste can occur when trials are conducted in the wrong
      populations. Vitamin D deficient populations are most likely to benefit from
      vitamin D supplementation. We investigated waste attributable to randomised
      controlled trials (RCTs) of supplementation in populations that were not vitamin
      D deficient. METHODS: In December 2015, we searched Pubmed, recent systematic
      reviews, and three trial registries for RCTs of vitamin D with clinical endpoints
      in adults, and 25-hydroxvitamin D (25OHD) survey data relevant to large (N >=
      1000) RCTs. We investigated the proportion of RCTs that studied vitamin D
      deficient populations, temporal trends in baseline 25OHD, and whether
      investigators in large RCTs considered relevant 25OHD survey data or systematic
      reviews in their trial justifications. RESULTS: Of 137 RCTs of vitamin D with
      clinical endpoints, 118 (86%) reported baseline mean/median 25OHD, which was <
      25, 25-49, 50-74, and >= 75 nmol/L in 12 (10%), 62 (53%), 36 (31%), and 8 (7%)
      RCTs, respectively. In 70% of RCTs, baseline 25OHD was > 40 nmol/L. Baseline
      25OHD increased over time. Before 2006, 38%, 62%, 0% and 0% of RCTs had baseline
      25OHD < 25, 25-49, 50-74, and >= 75 nmol/L respectively; in 2011-15, the
      respective proportions were 9%, 49%, 37%, and 6%. Of 12 RCTs with baseline 25OHD
      < 25 nmol/L, 8 had neutral findings. Of 25 large RCTs (18 completed, 7 ongoing),
      1 was undertaken in a vitamin D deficient population, 3 in vitamin D insufficient
      populations, and 17 had, or probably will have, baseline 25OHD > 40 nmol/L. 44%
      (8/18) of large completed RCTs cited relevant prior population 25OHD data, and
      only 3/10 (30%) relevant prior systematic reviews. CONCLUSIONS: Up to 70% of RCTs
      of vitamin D with clinical endpoints, 71% of large completed RCTs, and 100% of
      ongoing large RCTs could be considered research waste because they studied
      cohorts that were not vitamin D deficient.

PMID- 30285730
TI  - Fagus sylvatica seedlings show provenance differentiation rather than adaptation
      to soil in a transplant experiment.
AB  - BACKGROUND: Understanding and predicting the response of tree populations to
      climate change requires understanding the pattern and scale of their adaptation.
      Climate is often considered the major driver of local adaptation but, although
      biotic factors such as soil pathogens or mutualists could be as important, their
      role has typically been neglected. Biotic drivers might also interact with
      climate to affect performance and mycorrhizae, in particular, are likely to play
      a key role in determining drought resistance, which is important in the context
      of adaptation to future environmental change. To address these questions, we
      performed a fully reciprocal soil-plant transplant experiment using Fagus
      sylvatica seedlings and soils from three regions in Germany. To separate the
      biotic and abiotic effects of inoculation, half of the plants were inoculated
      with natural soil from the different origins, while the rest were grown on
      sterilized substrate. We also imposed a drought stress treatment to test for
      interactions between soil biota and climate. After 1 year of growth, we measured
      aboveground biomass of all seedlings, and quantified mycorrhizal colonization for
      a subset of the seedlings, which included all soil-plant combinations, to
      disentangle the effect of mycorrhiza from other agents. RESULTS: We found that
      plant origin had the strongest effect on plant performance, but this interacted
      with soil origin. In general, trees showed a slight tendency to produce less
      aboveground biomass on local soils, suggesting soil antagonists could be causing
      trees to be maladapted to their local soils. Consistently, we found lower
      mycorrhizal colonization rate under local soil conditions. Across all soils,
      seedlings from low elevations produced more annual biomass than middle (+ 290%)
      and high (+ 97%) elevations. Interestingly, mycorrhizal colonization increased
      with drought in the two provenances that showed higher drought tolerance, which
      supports previous results showing that mycorrhizae can increase drought
      resistance. CONCLUSIONS: Our findings suggest that soil communities play a role
      in affecting early performance of temperate trees, although this role may be
      smaller than that of seed origin. Also, other effects, such as the positive
      response to generalists or negative interactions with soil biota may be as
      important as the highly specialized mycorrhizal associations.

PMID- 30285731
TI  - Impact of herpes zoster and postherpetic neuralgia on the quality of life of
      Germans aged 50 or above.
AB  - BACKGROUND: Herpes zoster (HZ) is a painful dermatomal rash caused by
      reactivation of latent varicella zoster virus surviving in the patient's sensory
      ganglia after a previous episode of varicella. The incidence of HZ increases
      markedly with age as does the proportion of HZ patients who develop postherpetic
      neuralgia (PHN) with often severe and debilitating pain persisting for months and
      even years. This prospective study aimed to assess the impact of HZ and PHN on
      the quality of life (QoL) of individuals aged >= 50 years in Germany. METHODS:
      Patients were recruited when consulting primary care physicians for a first HZ
      episode. PHN was defined as a 'worst' pain score >= 3 on the Zoster Brief Pain
      Inventory (ZBPI) scale persisting or appearing 90 days or more after rash onset.
      PHN-cases were followed for up to nine months after rash onset. The interference
      of pain with patients' ability to carry out normal activities was assessed by the
      ZBPI activities of daily living (ADL) scale and QoL by the EuroQoL five-dimension
      scale (EQ-5D) utility score. RESULTS: Of 513 patients enrolled, 61 (11.9%)
      developed PHN. At HZ onset, the mean ZBPI worst pain score of all patients was
      5.1, the least square (LS)means estimates of the ZBPI ADL and EQ-5D utility
      scores were 2.970 and 0.740, respectively. Over three months follow-up, the pain
      scores decreased and the QoL increased monotonically across all age groups. At
      Day 90, the mean ZBPI worst pain score of the PHN patients was 4.4, while the
      LSmeans estimates of the ZBPI ADL and EQ-5D utility scores were 2.899 and 0.826,
      respectively. For patients with PHN persisting at nine months, the pain scores
      and QoL remained unchanged over the six months following the development of PHN.
      CONCLUSION: HZ and PHN had a substantial impact on the patients' QoL and ability
      to function in their normal activities. There was a clear association in time
      between the evolution of pain and estimated QoL. The impact on ADL and QoL did
      not vary with age.

PMID- 30285728
TI  - The TRAX, DISC1, and GSK3 complex in mental disorders and therapeutic
      interventions.
AB  - Psychiatric disorders (such as bipolar disorder, depression, and schizophrenia)
      affect the lives of millions of individuals worldwide. Despite the tremendous
      efforts devoted to various types of psychiatric studies and rapidly accumulating
      genetic information, the molecular mechanisms underlying psychiatric disorder
      development remain elusive. Among the genes that have been implicated in
      schizophrenia and other mental disorders, disrupted in schizophrenia 1 (DISC1)
      and glycogen synthase kinase 3 (GSK3) have been intensively investigated. DISC1
      binds directly to GSK3 and modulates many cellular functions by negatively
      inhibiting GSK3 activity. The human DISC1 gene is located on chromosome 1 and is
      highly associated with schizophrenia and other mental disorders. A recent study
      demonstrated that a neighboring gene of DISC1, translin-associated factor X
      (TRAX), binds to the DISC1/GSK3beta complex and at least partly mediates the
      actions of the DISC1/GSK3beta complex. Previous studies also demonstrate that
      TRAX and most of its interacting proteins that have been identified so far are
      risk genes and/or markers of mental disorders. In the present review, we will
      focus on the emerging roles of TRAX and its interacting proteins (including DISC1
      and GSK3beta) in psychiatric disorders and the potential implications for
      developing therapeutic interventions.

PMID- 30285733
TI  - Secondary spontaneous pneumothorax in patients with sarcoma treated with
      Pazopanib, a case control study.
AB  - BACKGROUND: The tyrosine kinase inhibitor pazopanib is used for treatment of
      sarcoma. Recent studies have suggested that the use of pazopanib may lead to the
      development of pneumothorax, an unexpected adverse effect in patients with
      sarcoma metastatic to the chest. METHODS: We conducted a retrospective case
      control study of patients with sarcoma with metastases to the chest with
      pneumothorax (cases) and without pneumothorax (controls). The control population
      was selected from tumor registry in a 1:4 (cases to controls) ratio. The primary
      outcome of interest was the association between pazopanib and pneumothorax risk
      in patients with sarcoma metastatic to the chest. Secondary objective was to
      evaluate risk factors for pneumothorax. RESULTS: We identified 41 cases and 164
      controls. Using purposeful selection method the odds of developing pneumothorax
      while being on pazopanib was not significant in univariate (p = .06) and
      multivariable analysis (p = .342). On univariate analysis risk factors of
      pneumothorax in patients with sarcoma were age, male sex, African American race,
      the presence of cavitary lung nodules/masses, and the presence of pleural-based
      nodules/masses. On multivariate analysis, only the presence of cavitary lung
      nodules/masses (P < .001) and the presence of pleural-based nodules/masses (P <
      .001) remained as risk factors for developing pneumothorax. CONCLUSION: Pazopanib
      does not increase the risk of pneumothorax in patients with sarcoma and evidence
      of metastatic disease to the chest. Presence of cavitary lung nodules/masses and
      the presence of pleural-based nodules/masses were found to be risk factors for
      pneumothorax.

PMID- 30285732
TI  - Utility of circulating tumor DNA in cancer diagnostics with emphasis on early
      detection.
AB  - Various recent studies have focused on analyzing tumor genetic material released
      into the blood stream, known as circulating tumor DNA (ctDNA). Herein, we
      describe current research on the application of ctDNA to cancer management,
      including prognosis determination, monitoring for treatment efficacy/relapse,
      treatment selection, and quantification of tumor size and disease burden.
      Specifically, we examine the utility of ctDNA for early cancer diagnostics
      focusing on the development of a blood test to detect cancer in asymptomatic
      individuals by sequencing and analyzing mutations in ctDNA. Next, we discuss the
      prospect of using ctDNA to test for cancer, and present our calculations based on
      previously published empirical findings in cancer and prenatal diagnostics. We
      show that very early stage (asymptomatic) tumors are not likely to release enough
      ctDNA to be detectable in a typical blood draw of 10 mL. Data are also presented
      showing that mutations in circulating free DNA can be found in healthy
      individuals and will likely be very difficult to distinguish from those
      associated with cancer.We conclude that the ctDNA test, in addition to its high
      cost and complexity, will likely suffer from the same issues of low sensitivity
      and specificity as traditional biomarkers when applied to population screening
      and early (asymptomatic) cancer diagnosis.

PMID- 30285734
TI  - Long-term feeding with high plant protein based diets in gilthead seabream
      (Sparus aurata, L.) leads to changes in the inflammatory and immune related gene
      expression at intestinal level.
AB  - BACKGROUND: In order to ensure sustainability of aquaculture production of
      carnivourous fish species such as the gilthead seabream (Sparus aurata, L.), the
      impact of the inclusion of alternative protein sources to fishmeal, including
      plants, has been assessed. With the aim of evaluating long-term effects of
      vegetable diets on growth and intestinal status of the on-growing gilthead
      seabream (initial weight = 129 g), three experimental diets were tested: a strict
      plant protein-based diet (VM), a fishmeal based diet (FM) and a plant protein
      based diet with 15% of marine ingredients (squid and krill meal) alternative to
      fishmeal (VM+). Intestines were sampled after 154 days. Besides studying growth
      parameters and survival, the gene expression related to inflammatory response,
      immune system, epithelia integrity and digestive process was analysed in the
      foregut and hindgut sections, as well as different histological parameters in the
      foregut. RESULTS: There were no differences in growth performance (p = 0.2703)
      and feed utilization (p = 0.1536), although a greater fish mortality was recorded
      in the VM group (p = 0.0141). In addition, this group reported a lower expression
      in genes related to pro-inflammatory response, as Interleukine-1beta (il1beta, p
      = 0.0415), Interleukine-6 (il6, p = 0.0347) and cyclooxigenase-2 (cox2, p =
      0.0014), immune-related genes as immunoglobulin M (igm, p = 0.0002) or bacterial
      defence genes as alkaline phosphatase (alp, p = 0.0069). In contrast, the VM+
      group yielded similar survival rate to FM (p = 0.0141) and the gene expression
      patterns indicated a greater induction of the inflammatory and immune markers
      (il1beta, cox2 and igm). However, major histological changes in gut were not
      detected. CONCLUSIONS: Using plants as the unique source of protein on a long
      term basis, replacing fishmeal in aqua feeds for gilthead seabream, may have been
      the reason of a decrease in the level of different pro-inflammatory mediators
      (il1 beta, il6 and cox2) and immune-related molecules (igm and alp), which
      reflects a possible lack of local immune response at the intestinal mucosa,
      explaining the higher mortality observed. Krill and squid meal inclusion in
      vegetable diets, even at low concentrations, provided an improvement in nutrition
      and survival parameters compared to strictly plant protein based diets as VM,
      maybe explained by the maintenance of an effective immune response throughout the
      assay.

PMID- 30285735
TI  - Staff empowerment and engagement in a magnet(r) recognized and joint commission
      international accredited academic centre in Belgium: a cross-sectional survey.
AB  - BACKGROUND: A substantial number of studies linked aspects of a balanced, healthy
      and supportive nurse practice environment with quality and patient safety. To
      what extent balanced work characteristics such as social capital, decision
      latitude and workload are relevant for all staff engaged in patient care
      including healthcare and medical staff in a Magnet Recognized and Joint
      Commission International accredited academic centre is unclear. The study aim is
      to investigate associations between work characteristics such as social capital,
      decision latitude and workload, work engagement and feelings of burnout as
      explanatory variables and job satisfaction, turnover intentions and perceived
      quality of care as dependent variables in a study population of nursing,
      healthcare and medical staff taken in account generation differences. METHODS:
      Hierarchical regression analysis estimated strength of associations with
      demographic characteristics (block-1), professional category (block-2), work
      characteristics (block-3) and work engagement or burnout dimensions (block-4) as
      explanatory variables of job satisfaction and turnover intention and quality of
      care as outcome variables. RESULTS: The study confirmed and extended previous
      study findings demonstrating positive impact on staff' job outcomes and assessed
      quality of care by balanced work characteristics such as social capital, decision
      latitude and workload in nursing staff (N = 864), healthcare staff (N = 131) and
      medical staff (N = 241). Generational characteristics and professional category
      were associated with turnover intentions and less favorable assessed quality of
      care, respectively. Explained variances of studied models ranged from 14.4 to
      45.7%. CONCLUSION: Engaging and committing staff to promote excellent patient
      outcomes in daily interdisciplinary practice works through clear frameworks,
      methods and resources supported by governance and policy structure that makes
      outcomes visible and accountable.

PMID- 30285736
TI  - Good response to PAH-targeted drugs in a PVOD patient carrying Biallelic EIF2AK4
      mutation.
AB  - Pulmonary veno-occlusive disease (PVOD) is a rare and fatal cause of pulmonary
      arterial hypertension (PAH). Different from other types of PAH, PVOD patients
      have a dismal prognosis because of the progressive nature of pulmonary vascular
      involvement and fatal pulmonary edema induced by PAH-targeted drugs. Lung
      transplantation is the only choice for these patients. In a recent article
      published in the journal, Yang and his colleagues found pulmonary edema was not
      demonstrated in 2 of the 6 PVOD patients injected with prostacyclin analogues (a
      kind of PAH-targeted drug). Regretfully, none of these 6 patients underwent
      microscopic examination of lung tissues. Here, we reported a sporadic PVOD
      patient evidenced by pathology and EIF2AK4 biallelic mutation. The patient was
      followed over the course of 3 years in our center. During the 3 years, he was
      admitted into our hospital for many times for the acute exacerbation of pulmonary
      hypertension. However, after treatment with many kinds of PAH-targeted drugs, the
      pulmonary hypertension was in control and he feel better every time. The present
      patient displayed different treatment response comparing with previous reports.
      It suggests that PVOD is a heterogeneity population and different patients have
      different characteristics including clinical manifestation, genomics, treatment
      response et al. How to pick off this portion of patients timely is the core
      issue. Lots of important works are necessary to answer this question. However, we
      can see a glimmer of hope form this patient at least.

PMID- 30285737
TI  - Sense and sensibility: on the diagnostic value of control chart rules for
      detection of shifts in time series data.
AB  - BACKGROUND: The aim of this study was to quantify and compare the diagnostic
      value of The Western Electric (WE) statistical process control (SPC) chart rules
      and the Anhoej rules for detection of non-random variation in time series data in
      order to make recommendations for their application in practice. METHODS: SPC
      charts are point-and-line graphs showing a measure over time and employing
      statistical tests for identification of non-random variation. In this study we
      used simulated time series data with and without non-random variation introduced
      as shifts in process centre over time. The primary outcome was likelihood ratios
      of combined tests. Likelihood ratios are useful measures of a test's ability to
      discriminate between the true presence or absence of a specific condition.
      RESULTS: With short data series (10 data points), the WE rules 1-4 combined and
      the Anhoej rules alone or combined with WE rule 1 perform well for identifying or
      excluding persistent shifts in the order of 2 SD. For longer data series, the
      Anhoej rules alone or in combination with the WE rule 1 seem to perform slightly
      better than the WE rules combined. However, the choice of which and how many
      rules to apply in a given situation should be made deliberately depending on the
      specific purpose of the SPC analysis and the number of available data points.
      CONCLUSIONS: Based on these results and our own practical experience, we suggest
      a stepwise approach to SPC analysis: Start with a run chart using the Anhoej
      rules and with the median as process centre. If, and only if, the process shows
      random variation at the desired level, apply the 3-sigma rule in addition to the
      Anhoej rules using the mean as process centre.

PMID- 30285738
TI  - Variability in antifungal utilization among neonatal, pediatric, and adult
      inpatients in academic medical centers throughout the United States of America.
AB  - BACKGROUND: Identification of factors associated with antifungal utilization in
      neonatal, pediatric, and adult patient groups is needed to guide antifungal
      stewardship initiatives in academic medical centers. METHODS: For this hospital
      level analysis, we analyzed antifungal use in hospitals across the United States
      of America, excluding centers only providing care for hematology/oncology
      patients. Analysis of variance was used to compare antifungal use between patient
      groups. Three multivariable linear regression models were used to determine
      independent factors associated with antifungal use in the neonatal, pediatric,
      and adult patient groups. RESULTS: For the neonatal, pediatric, and adult patient
      groups, 54, 44, and 60 hospitals were included, respectively. Total antifungal
      use was significantly lower in the neonatal patient group (14 days of therapy
      (DOT)/1000 patient days (PDs) versus 76 in pediatrics and 74 in adults, p <
      0.05). There were no significant associations identified with total antifungal
      DOT/1000 PDs in the neonatal patient group (model R2 = 0.11). In the pediatric
      patient group (model R2 = 0.55), admission to immunosuppressed service lines and
      total broad-spectrum antibiotic use were positively associated with total
      antifungal use (coefficients of 1.95 and 0.41, both p < 0.05). In the adult
      patient group (model R2 = 0.79), admission to immunosuppressed service lines,
      total invasive fungal infections, and total broad-spectrum antibiotic use were
      positively associated with total antifungal use (coefficients of 5.08, 5.17, and
      0.137, all p < 0.05). CONCLUSIONS: Variability in antifungal use in the neonatal
      group could not be explained well, whereas factors were associated with
      antifungal use in the adult and pediatric patient groups. These data can help
      guide antifungal stewardship initiatives.

PMID- 30285740
TI  - Correction to: Oral administration of inactivated porcine epidemic diarrhea virus
      activate DCs in porcine Peyer's patches.
AB  - The original article [1] contained an error whereby the leftmost graph in Fig. 1A
      mistakenly had its x-axis labelled as 'CFST'; this has now been corrected to
      'CFSE'.

PMID- 30285741
TI  - Rectal, central venous, gastric and bladder pressures versus esophageal pressure
      for the measurement of cough strength: a prospective clinical comparison.
AB  - BACKGROUND: Cough pressure, an expression of expiratory muscle strength, is
      usually measured with esophageal or gastric balloons, but these invasive
      catheters can be uncomfortable for the patient or their placement impractical.
      Because pressure in the thorax and abdomen are expected to be similar during a
      cough, we hypothesized that measurement at other thoracic or abdominal locations
      might also be similar as well as useful in clinical scenarios. This study aimed
      to compare cough pressures measured at thoracic and abdominal sites that could
      serve as alternatives to esophageal pressures (Pes). METHODS: Nine patients
      scheduled for laparotomy were asked to cough as forcefully as possible from total
      lung capacity in supine position. Three cough maneuvers were performed while Pes
      (the gold standard) as well as gastric, central venous, bladder and rectal
      pressures (Pga, Pcv, Pbl, and Prec, respectively) were measured simultaneously.
      The intraclass correlation coefficient (ICC) was used to evaluate the
      repeatability of the measurements in each patient at each site and evaluate
      agreement between alternative sites (Pga, Pcv, Pbl, and Prec) and Pes. Bland
      Altman plots were used to compare Pes and the measurements at the other sites.
      RESULTS: Median (first quartile, third quartile) maximum pressures were as
      follows: Pes 112 (89,148), Pga 105 (92,156), Pcv 102 (91,149), Pbl 118 (93,157),
      and Prec 103 (88,150) cmH2O. The ICCs showed excellent within-site repeatability
      of the measurements (p < 0.001) and excellent agreement between alternative sites
      and Pes (p < 0.004). The Bland-Altman plots showed minimal differences between
      Pes, Pga, Pcv, and Prec. However, Pbl was higher than the other pressures in most
      patients, and the difference between Pes and Pbl was slightly larger.
      CONCLUSIONS: Cough pressure can be measured in the esophagus, stomach, superior
      vena cava or rectum, since their values are similar. It can also be measured in
      the bladder, although the value will be slightly higher. These results
      potentially facilitate the assessment of dynamic expiratory muscle strength with
      fewer invasive catheter placements in most hospitalized patients, thus providing
      an option that will be particularly useful in those undergoing thoracic or
      abdominal surgery. TRIAL REGISTRATION: NCT02957045 registered at November 7,
      2016. Retrospectively registered.

PMID- 30285739
TI  - VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor
      WWOX.
AB  - BACKGROUND: The WW domain-containing oxidoreductase (WWOX) gene, frequently
      altered in breast cancer, encodes a tumor suppressor whose function is mediated
      through its interactions with cancer-related proteins, such as the pro-apoptotic
      protein p73alpha. RESULTS: To better understand the involvement of WWOX in breast
      tumorigenesis, we performed a yeast two-hybrid screen and co-immunoprecipitation
      assays to identify novel partners of this protein. We characterized the vesicular
      overexpressed in cancer pro-survival protein 1 (VOPP1) as a new regulator of
      WWOX. In breast cancer cells, VOPP1 sequestrates WWOX in lysosomes, impairs its
      ability to associate with p73alpha, and inhibits WWOX-dependent apoptosis.
      Overexpressed VOPP1 potentiates cellular transformation and enhances the growth
      of transplanted tumors in vivo. VOPP1 is overexpressed in breast tumors,
      especially in tumors that retain WWOX. Moreover, increased expression of VOPP1 is
      associated with reduced survival of patients with WWOX-positive, but not with
      WWOX-negative, tumors. CONCLUSIONS: These findings emphasize the importance of
      the sequestration of WWOX by VOPP1 in addition to WWOX loss in breast tumors and
      define VOPP1 as a novel oncogene promoting breast carcinogenesis by inhibiting
      the anti-tumoral effect of WWOX.

PMID- 30285742
TI  - Developing and evaluating clinical leadership interventions for frontline
      healthcare providers: a review of the literature.
AB  - BACKGROUND: The importance of clinical leadership in ensuring high quality
      patient care is emphasized in health systems worldwide. Of particular concern are
      the high costs to health systems related to clinical litigation settlements. To
      avoid further cost, healthcare systems particularly in High-Income Countries
      invest significantly in interventions to develop clinical leadership among
      frontline healthcare workers at the point of care. In Low-Income Countries
      however, clinical leadership development is not well established. This review of
      the literature was conducted towards identifying a model to inform clinical
      leadership development interventions among frontline healthcare providers,
      particularly for improved maternal and newborn care. METHODS: A structural
      literature review method was used, articles published between 2004 and 2017 were
      identified from search engines (Google Scholar and EBSCOhost). Additionally,
      electronic databases (CINHAL, PubMed, Medline, Academic Search Complete, Health
      Source: Consumer, Health Source: Nursing/Academic, Science Direct and Ovid(r)),
      electronic journals, and reference lists of retrieved published articles were
      also searched. RESULTS: Employing pre-selected criteria, 1675 citations were
      identified. After screening 50 potentially relevant full-text papers for
      eligibility, 24 papers were excluded because they did not report on developing
      and evaluating clinical leadership interventions for frontline healthcare
      providers, 2 papers did not have full text available. Twenty-four papers met the
      inclusion criteria for review. Interventions for clinical leadership development
      involved the development of clinical skills, leadership competencies, teamwork,
      the environment of care and patient care. Work-based learning with experiential
      teaching techniques is reported as the most effective, to ensure the clinical
      leadership development of frontline healthcare providers. CONCLUSIONS: All
      studies reviewed arose in High-Income settings, demonstrating the need for
      studies on frontline clinical leadership development in Low-and Middle-Income
      settings. Clinical leadership development is an on-going process and must target
      both novice and veteran frontline health care providers. The content of clinical
      leadership development interventions must encompass a holistic conceptualization
      of clinical leadership, and should use work-based learning, and team-based
      approaches, to improve clinical leadership competencies of frontline healthcare
      providers, and overall service delivery.

PMID- 30285743
TI  - High dissolved oxygen tension triggers outer membrane vesicle formation by
      Neisseria meningitidis.
AB  - BACKGROUND: Outer membrane vesicles (OMVs) are nanoparticles released by Gram
      negative bacteria and can be used as vaccines. Often, detergents are used to
      promote release of OMVs and to remove the toxic lipopolysaccharides.
      Lipopolysaccharides can be detoxified by genetic modification such that vesicles
      spontaneously produced by bacteria can be directly used as vaccines. The use of
      spontaneous OMVs has the advantage that no separate extraction step is required
      in the purification process. However, the productivity of spontaneous OMVs by
      bacteria at optimal growth conditions is low. One of many methods for increasing
      OMV formation is to reduce the linkage of the outer membrane to the peptidoglycan
      layer by knocking out the rmpM gene. A previous study showed that for Neisseria
      meningitidis this resulted in release of more OMVs. Furthermore, cysteine
      depletion was found to trigger OMV release and at the same time cause reduced
      growth and oxidative stress responses. Here we study the effect of growth rate
      and oxidative stress on OMV release. RESULTS: First, we identified using
      chemostat and accelerostat cultures of N. meningitidis that increasing the growth
      rate from 0.03 to 0.18 h-1 has a limited effect on OMV productivity. Thus, we
      hypothesized that oxidative stress is the trigger for OMV release and that
      oxidative stress can be introduced directly by increasing the dissolved oxygen
      tension of bacterial cultures. Slowly increasing oxygen concentrations in a N.
      meningitidis changestat showed that an increase from 30 to 150% air saturation
      improved OMV productivity four-fold. Batch cultures controlled at 100% air
      saturation increased OMV productivity three-fold over batch cultures controlled
      at 30% air saturation. CONCLUSION: Increased dissolved oxygen tension induces the
      release of outer membrane vesicles in N. meningitidis cultures. Since oxygen
      concentration is a well-controlled process parameter of bacterial cultures, this
      trigger can be applied as a convenient process parameter to induce OMV release in
      bacterial cultures. Improved productivity of OMVs not only improves the
      production costs of OMVs as vaccines, it also facilitates the use of OMVs as
      adjuvants, enzyme carriers, or cell-specific drug delivery vehicles.

PMID- 30285744
TI  - Cost-effectiveness analysis of doctor-pharmacist collaborative prescribing for
      venous thromboembolism in high risk surgical patients.
AB  - BACKGROUND: Current evidence to support cost effectiveness of doctor- pharmacist
      collaborative prescribing is limited. Our aim was to evaluate inpatient
      prescribing of venous thromboembolism (VTE) prophylaxis by a pharmacist in an
      elective surgery pre-admission clinic against usual care, to measure any benefits
      in cost to the healthcare system and quality adjusted life years (QALYs) of
      patients. METHOD: A decision tree model was developed to assess cost
      effectiveness of pharmacist prescribing compared with usual care for VTE
      prophylaxis in high risk surgical patients. Data from the literature was used to
      inform decision-tree probabilities, utility, and cost outcomes. In the
      intervention arm, a pharmacist prescribed patient's regular medications,
      documented a VTE risk assessment and prescribed VTE prophylaxis. In the usual
      care arm, resident medical officers were responsible for prescribing regular
      medications, and for risk assessment and prescribing of VTE prophylaxis. The base
      scenario assessed the cost effectiveness of a pre-existing pre-admission clinic
      pharmacy service that takes on a collaborative prescribing role. The alternative
      scenario assessed the benefits of introducing a pre-admission clinic pharmacy
      service where previously there had not been one. Probabilistic sensitivity
      analysis was conducted to explore uncertainty in the model. RESULTS: In both the
      base-case scenario and the alternative scenario pharmacist prescribing resulted
      in an increase in the proportion of patients adequately treated and a decrease in
      the incidence of VTE resulting in cost savings and improvement in quality of
      life. The cost savings were $31 (95% CI: -$97, $160) per patient in the base
      scenario and $12 (95% CI: -$131, $155) per patient in the alternative scenario.
      In both scenarios the pharmacist-doctor prescribing resulted in an increase in
      QALYs of 0.02 (95% CI: -0.01, 0.005) per patient. The probability of being cost
      effective at a willingness to pay off $40,000 was 95% in the base scenario and
      94% in the alternative scenario. CONCLUSION: Delegation of the prescribing of VTE
      prophylaxis for high risk surgical patients to a pharmacist prescriber in PAC, as
      part of a designated scope of practice, would result in fewer cases of VTE and
      associated lower costs to the healthcare system and increased QALYs gained by
      patients. TRIAL REGISTRATION: Pre admission clinic study registered with ANZCTR
      ACTR Number ACTRN12609000426280 .

PMID- 30285745
TI  - Demographic, psychosocial and clinical factors associated with postpartum
      depression in Kenyan women.
AB  - BACKGROUND: Few longitudinal studies have examined associations between risk
      factors during pregnancy and mental health outcomes during the postpartum period.
      We used a cohort study design to estimate the prevalence, incidence and
      correlates of significant postpartum depressive symptoms in Kenyan women.
      METHODS: We recruited adult women residing in an urban, resource-poor setting and
      attending maternal and child health clinics in two public hospitals in Nairobi,
      Kenya. A translated Kiswahili Edinburgh Postpartum Depression Scale was used to
      screen for depressive symptoms at baseline assessment in the 3rd trimester and
      follow up assessment at 6-10 weeks postpartum. Information was collected on
      potential demographic, psychosocial and clinical risk variables. Potential risk
      factors for postpartum depression were evaluated using multivariate logistic
      regression analysis. RESULTS: Out of the 171 women who were followed up at 6-10
      weeks postpartum, 18.7% (95% CI: 13.3-25.5) were found to have postpartum
      depression using an EPDS cut off of 10. In multivariate analyses, the odds of
      having postpartum depression was increased more than seven-fold in the presence
      of conflict with partner (OR = 7.52, 95% CI: 2.65-23.13). The association between
      antepartum and postpartum depression was quite strong but did not reach
      statistical significance (OR = 3.37, 95% CI: 0.98-11.64). CONCLUSIONS: The high
      prevalence of significant postnatal depressive symptoms among Kenyan women
      underscores the need for addressing this public health burden. Depression
      screening and psychosocial support interventions that address partner conflict
      resolution should be offered as part of maternal health care.

PMID- 30285746
TI  - Patient capacity for self-care in the medical record of patients with chronic
      conditions: a mixed-methods retrospective study.
AB  - BACKGROUND: Patients with chronic conditions must mobilize capacity to access and
      use healthcare and enact self-care. In order for clinicians to create feasible
      treatment plans with patients, they must appreciate the limits and possibilities
      of patient capacity. This study seeks to characterize the amount, nature, and
      comprehensiveness of the information about patient capacity documented in the
      medical record. METHODS: In this mixed-methods study, we extracted notes about 6
      capacity domains from the medical records of 100 patients receiving care from 15
      primary care clinicians at a single practice. Using a generalized linear model to
      account for repeated measures across multiple encounters, we calculated the rate
      of documented domains per encounter per patient adjusted for appointment type and
      number. Following quantitative analyses, we purposefully selected records to
      conduct inductive content analysis. RESULTS: After adjusting for number of
      appointments and appointment type, primary care notes contained the most mentions
      of capacity. Physical capacity was most noted, followed by personal, emotional,
      social, financial, and environmental. Qualitatively, we found three documentation
      patterns: patients with broad capacity notes, patients with predominantly
      physical domain capacity notes, and patients with capacity notes mostly in
      domains other than physical. Records contained almost no mention of patients'
      environmental or financial capacity, or of how they coped with capacity
      limitations. Rarely, did notes ever mention how well patients interacted with
      their social network or what support they provided to the patient in managing
      their health. CONCLUSION: Medical records scarcely document patient capacity.
      This may impair the ability of clinicians to determine how patients can handle
      patient work, at what point patient capacity might become overwhelmed leading to
      poor adherence and health outcomes, and how best to craft feasible treatment
      programs that patients can implement with high fidelity.

PMID- 30285747
TI  - In silico characterization of the global Geobacillus and Parageobacillus
      secretome.
AB  - BACKGROUND: Geobacillus and Parageobacillus are two ecologically diverse
      thermophilic genera within the phylum Firmicutes. These taxa have long been of
      biotechnological interest due to their ability to secrete thermostable enzymes
      and other biomolecules that have direct applications in various industrial and
      clinical fields. Despite the commercial and industrial interest in these
      microorganisms, the full scope of the secreted protein, i.e. the secretome, of
      Geobacillus and Parageobacillus species remains largely unexplored, with most
      studies focusing on single enzymes. A genome-wide exploration of the global
      secretome can provide a platform for understanding the extracellular functional
      "protein cloud" and the roles that secreted proteins play in the survival and
      adaptation of these biotechnologically relevant organisms. RESULTS: In the
      present study, the global secretion profile of 64 Geobacillus and Parageobacillus
      strains, comprising 772 distinct proteins, was predicted using comparative
      genomic approaches. Thirty-one of these proteins are shared across all strains
      used in this study and function in cell-wall/membrane biogenesis as well as
      transport and metabolism of carbohydrates, amino acids and inorganic ions. An
      analysis of the clustering patterns of the secretomes of the 64 strains according
      to shared functional orthology revealed a correlation between the secreted
      profiles of different strains and their phylogeny, with Geobacillus and
      Parageobacillus species forming two distinct functional clades. CONCLUSIONS: The
      in silico characterization of the global secretome revealed a metabolically
      diverse set of secreted proteins, which include proteases, glycoside hydrolases,
      nutrient binding proteins and toxins.

PMID- 30285748
TI  - The moderate predictive value of serial serum CRP and PCT levels for the
      prognosis of hospitalized community-acquired pneumonia.
AB  - BACKGROUND: To predict the prognosis by observing the dynamic change of C
      reactive protein (CRP) and procalcitonin (PCT) for hospitalized community
      acquired pneumonia (CAP). METHODS: The data were collected from January to
      December 2017 from the first affiliated Hospital of Zhengzhou University.
      Demographic and clinical patient information including age, length of hospital
      stay and Charlson Comorbidity Index (CCI) were recorded. Blood samples were taken
      for CRP, PCT, and white blood cell count (WBC). Receiver Operating Characteristic
      (ROC) curve was used to verify each biomarker's association with the prognosis of
      pneumonia. RESULTS: A total of 350 patients were enrolled in the study. The 30
      day mortality was 10.86%. Serial serum CRP3, CRP5, PCT3, PCT5 and PCT5c levels
      were statistically lower in CAP survivors than non-survivors. CRP3c < 0, CRP5c <
      0 and PCT5c < 0 were observed with a statistically lower frequency in patients
      with 30-day mortality and initial treatment failure. The AUC for 30-day mortality
      for serial CRP levels combined with CRP clearances was 0.85 (95% CI 0.77-0.92),
      as compared to an AUC of 0.81 (95% CI 0.73-0.9) for serial PCT levels combined
      with PCT clearances. CONCLUSIONS: Serum serial CRP and PCT levels had moderate
      predictive value for hospitalized CAP prognosis. The dynamic CRP and PCT changes
      may potentially be used in the future to predict hospitalized CAP prognosis.

PMID- 30285749
TI  - Co-culture of Bacillus amyloliquefaciens ACCC11060 and Trichoderma asperellum
      GDFS1009 enhanced pathogen-inhibition and amino acid yield.
AB  - BACKGROUND: Bacillus spp. are a genus of biocontrol bacteria widely used for
      antibiosis, while Trichoderma spp. are biocontrol fungi that are abundantly
      explored. In this study, a liquid co-cultivation of these two organisms was tried
      firstly. RESULTS AND DISCUSSION: Through liquid chromatography-mass
      spectrometry/mass spectrometry (LC-MS/MS), it was discovered that with an
      inoculation in the ratio of 1.9:1, the antimicrobial effect of the co-cultured
      fermentation liquor of Bacillus amyloliquefaciens ACCC11060 and Trichoderma
      asperellum GDFS1009 was found to be significantly higher than that of pure
      cultivation. A raise in the synthesis of antimicrobial substances contributed to
      this significant increase. Additionally, a co-culture with the inoculation of the
      two organisms in the ratio of 1:1 was found to enhance the production of specific
      amino acids. This technique could be further explored for either a large scale
      production of amino acids or could serve as a theoretical base for the generation
      of certain rare amino acids. CONCLUSIONS: This work clearly demonstrated that co
      cultivation of B. amyloliquefaciens ACCC11060 and T. asperellum GDFS1009 could
      produce more specific biocontrol substances and amino acids.

PMID- 30285750
TI  - Strategy to improve malaria surveillance system preventing transfusion
      transmitted malaria in blood banks using molecular diagnostic.
AB  - BACKGROUND: Malaria can be transmitted by blood transfusion through donations
      collected from asymptomatic or parasitic donors. The parasites are released into
      the bloodstream during its life cycle and will therefore be present in donated
      blood by infected individuals. All cases of transfusion-transmitted malaria (TTM)
      notified since 2005 in Brazil were fatal. A good screening tool for Plasmodium
      spp. detection in blood units must have a high detection threshold, and the
      prevention of TTM relies entirely on the exclusion of potentially infected
      donors. However, in Brazilian blood banks, the screening test relies on blood
      thick smears examination. METHODS: The molecular diagnostic based on
      mitochondrial DNA (mtDNA) using real time PCR (mt-qPCR) was improved to detect
      Plasmodium falciparum, Plasmodium vivax, and standardized for use in Plasmodium
      malariae. The analytic sensitivity of this mt-qPCR methodology was performed
      using a sample of P. vivax. RESULTS: The mt-qPCR was highly efficient, and the
      analytic sensitivity for P. vivax was determined (0.000006 parasites/uL). This
      method was tested to detect P. vivax and P. falciparum in individuals from two
      malaria-endemic areas in Brazil, Amazon region (Para and Rondonia states), the
      samples were collected in 10 reference units of two blood banks (Para/nine cities
      and Rondonia/Porto Velho), and parasites mtDNA were detected in 10 of 2224
      potential blood donors (0.45%). In all 10 positive samples, only P. vivax was
      detected. CONCLUSION: Molecular diagnostic using mt-qPCR was effective in
      revealing infected potential donors with good perspectives to be applied as
      screening routine of asymptomatic carriers for preventing transfusion-transmitted
      malaria in blood banks.

PMID- 30285751
TI  - Quantification of Clostridioides (Clostridium) difficile in feces of calves of
      different age and determination of predominant Clostridioides difficile ribotype
      033 relatedness and transmission between family dairy farms using multilocus
      variable-number tandem-repeat analysis.
AB  - BACKGROUND: Community acquired Clostridioides (Clostridium) difficile infection
      (CA-CDI) is a significant health problem in human and veterinary medicine.
      Animals are often considered as potential reservoirs for CA-CDI. In Europe,
      family farming is the most predominant farming operation, with a complex
      interaction between animals and the community. Therefore, it is pertinent to
      evaluate transmission patterns of C. difficile on such prominent European farming
      model. Fecal samples from calves (n = 2442) were collected biweekly over a period
      of one year on 20 mid-size family dairy farms. Environmental samples (n = 475)
      were collected in a three month interval. Clostridioides difficile was detected
      using qPCR in 243 fecal samples (243/2442); positive samples were then
      quantified. Association between prevalence/load of C. difficile and age of the
      calves was estimated with logistic regression model. Most common C. difficile
      isolate from calves (n = 76) and the environment (n = 14) was C. difficile
      ribotype 033, which was further analyzed using multilocus variable-number tandem
      repeat analysis (MLVA) to assess intra- and between-farm relatedness. RESULTS:
      Clostridioides difficile was detected in feces of calves less than 24 h old.
      Results showed a non-linear statistically significant decrease in shedding load
      of C. difficile with age (P < 0.0001). A nonlinear relationship was also
      established between the number of calves and the farm C. difficile prevalence,
      whereas the prevalence of C. difficile ribotype 033 increased linearly with the
      number of calves. MLVA revealed close intra-farm relatedness among C. difficile
      ribotypes 033. It also revealed that the between-farms close relatedness of C.
      difficile ribotypes 033 can be a direct result of farm to farm trade of calves.
      CONCLUSIONS: Implementation of better hygiene and management measures on farms
      may help decrease the risk of spreading CA-CDI between animals and the community.
      Trading calves older than 3 weeks would decrease the possibility C. difficile
      dissemination in the community because of lower prevalence and lower load of C.
      difficile in feces.

PMID- 30285752
TI  - Investigation of methicillin-resistant Staphylococcus aureus among clinical
      isolates from humans and animals by culture methods and multiplex PCR.
AB  - BACKGROUND: Staphylococcus aureus is responsible for large numbers of hospital
      related and community-acquired infections. In this study, we investigated the
      presence of S. aureus and methicillin-resistant S. aureus (MRSA) in 100 samples
      from animals (55 cattle, 36 dogs, and 9 cats) and 150 samples from hospitalized
      human patients. The samples were collected from healthy and diseased animals and
      from diseased humans and included milk, wound swab, pus, exudates, nasal swab and
      diabetic ulcer. Initially, S. aureus was isolated and identified by colony
      morphology, Gram staining, and biochemical tests (catalase and coagulase tests).
      The S. aureus-positive samples were examined by polymerase chain reaction (PCR)
      to determine their MRSA status. RESULTS: Of the 100 animal samples, 29 were
      positive for S. aureus. Four samples (13.8%) from dogs were MRSA-positive, but
      samples from cattle and cats were MRSA-negative. Of the 150 human samples we
      collected, 64 were S. aureus-positive and, of these, 34 (53.1%) were MRSA
      positive. Most (28%) of the MRSA samples were isolated from surgical wound swabs,
      followed by the pus from skin infections (11%), exudates from diabetic ulcers
      (6%), exudates from burns (4%), and aural swabs (3%). By contrast, a low MRSA
      detection rate (n = 4) was seen in the non-human isolates, where all MRSA
      bacteria were isolated from nasal swabs from dogs. The antimicrobials
      susceptibility testing results showed that S. aureus isolates with mecA genes
      showed resistance to penicillin (100%), oxacillin (100%), erythromycin (73.5%),
      ciprofloxacin (70.6%), and gentamicin (67.7%). The lowest resistance was found
      against ceftazidime, and no vancomycin-resistant isolates were obtained.
      CONCLUSIONS: We detected S. aureus and MRSA in both human and canine specimens.
      Isolates were found to be resistant to some of the antimicrobials available
      locally. MRSA carriage in humans and animals appears to be a great threat to
      effective antimicrobials treatment. The prudent use of antimicrobials will reduce
      the antimicrobial resistance. Our findings will help to find the most appropriate
      treatment and to reduce antimicrobial resistance in the future by implementing
      prudent use of antimicrobials. Further studies are required to better understand
      the epidemiology of MRSA human-animal inter-species transmission in Bangladesh.

PMID- 30285753
TI  - Determinants of having no general practitioner in Germany and the influence of a
      migration background: results of the German health interview and examination
      survey for adults (DEGS1).
AB  - BACKGROUND: It is aspired in the German healthcare system that general
      practitioners (GPs) act as initial contact for patients and guide through at all
      steps of medical treatment. This study aims at identifying factors associated
      with the odds of having no GP within the general population and especially among
      people with migration background. METHODS: This cross-sectional analysis was
      based on the "German Health Interview and Examination Survey for Adults" (DEGS1)
      conducted by the Robert Koch Institute. Descriptive analyses as well as multiple
      logistic regression models were performed to analyse the impact of a migration
      background, age, gender, residential area, socioeconomic status (SES) and other
      factors on having no GP among 7755 participants. RESULTS: 9.5% of the total study
      population and 14.8% of people with a migration background had no GP, especially
      men, adults living in big cities and without chronic diseases. The odds of not
      having a GP were higher for people with a two-sided migration background (aOR:
      1.90, 95% CI: 1.42-2.55). Among the population with a migration background,
      particularly young adults, men, people living in big cities and having a private
      health insurance showed higher odds to have no GP. CONCLUSIONS: It is necessary
      to investigate the causes of the differing utilization of healthcare of people
      with a migration background and, if necessary, to take measures for an equal
      access to healthcare for all population groups. Further research needs to be done
      to evaluate how to get young people into contact with a GP.

PMID- 30285754
TI  - Childbirth fear and related factors among pregnant and postpartum women in
      Malawi.
AB  - BACKGROUND: Childbirth fear is a health concern in women living in high-income
      countries; however, little is known about childbirth fear among women living in
      low-income countries like Malawi. In this study, we explored childbirth fear and
      associated factors among pregnant and postpartum women in Malawi. METHODS: A
      cross-sectional study of 152 pregnant and 153 postpartum women was conducted at a
      district hospital in Malawi. Participants were assessed for childbirth fear using
      the Wijma Delivery Expectancy/Experience Questionnaire (WDEQ). Demographic and
      obstetric variables were collected using a structured questionnaire. The
      Multidimensional Scale of Perceived Social Support (MSPSS) was used to measure
      social support. Using a multinomial logistic regression, factors related to
      childbirth fears were examined, namely demographic and obstetric characteristics,
      and social support. RESULTS: The mean age of participants was 26 (standard
      deviation: 6.4) years. During pregnancy, 39% women reported a low level of fear,
      41% reported moderate fear, and 20% reported high fear; while after birth, 49,
      41, and 10% women reported low, moderate, and high fear, respectively. Pregnant
      women who were illiterate (odds ratio (OR): 5.0, p < 0.01) or unemployed (OR:
      12.6, p < 0.01) were more likely to report moderate and high fear. Postpartum
      mothers who were illiterate (OR: 4.2, p < 0.01) or unemployed (OR: 11.8, p <
      0.01) were more likely to have moderate and high fear. Furthermore, postpartum
      women who sustained perineal tears had significantly higher odds of experiencing
      moderate (OR: 5.3, p < 0.01) or high (OR: 19.9, p < 0.01) fear than their
      counterparts. CONCLUSIONS: Childbirth fear is common in Malawi, and pregnant
      women are more likely to experience high levels of fear than postpartum women.
      This study highlighted the connection between childbirth fear with mother's
      education, employment, and perineal tears during delivery. Identifying and
      developing interventions for women with these associated characteristics is of
      clinical importance for the reduction of childbirth fear before and after
      childbirth in Malawi.

PMID- 30285755
TI  - Latina mothers as agents of change in children's eating habits: findings from the
      randomized controlled trial Entre Familia: Reflejos de Salud.
AB  - BACKGROUND: Few children consume sufficient servings of fruits and vegetables.
      Interventions aiming to improve children's dietary intake often target parent
      level factors, but limited research has examined the mediating role of parental
      factors on children's dietary intake. This study examined 10-month follow up data
      from the Entre Familia: Reflejos de Salud (Within the Family: Reflections of
      Health) trial to investigate (1) intervention effects on children's dietary
      intake, both sustained and new changes, and (2) whether changes in mothers'
      dietary intake, her parenting strategies, and behavioral strategies to promoting
      healthy eating in the home mediated changes in children's dietary intake.
      METHODS: Participants were 361 Mexican-origin families living in Imperial County,
      California. Families were randomly assigned to a 4-month dietary intervention or
      a delayed treatment control group. The intervention was delivered by promotoras
      (community health workers) via home visits and telephone calls. Assessments
      occurred at baseline, and 4- and 10-months post-baseline. RESULTS: At 10-months
      post-baseline, sustained intervention effects were observed on children's
      reported intake of varieties of vegetables, with differences getting larger over
      time. However, differential intervention effects on fast food were not sustained
      due to significant reductions in the control group compared with smaller changes
      in the intervention group. New intervention effects were observed on servings of
      sugar-sweetened beverages. However, the intervention continued to have no effect
      on children's reported fruit and vegetable servings, and varieties of fruits
      consumed. Mother-reported behavioral strategies to increase fiber and lower fat
      mediated the relationship between the intervention and children's intake of
      varieties of vegetables. Mothers' percent energy from fat and behavioral
      strategies to lower fat were mediators of children's daily servings of sugar
      sweetened beverages. CONCLUSIONS: This study suggests that a promotora-led family
      based intervention can provide mothers with skills to promote modest changes in
      children's diet. Examining the parent related mechanisms of change will inform
      future interventions on important targets for improving children's diet. TRIAL
      REGISTRATION: https://clinicaltrials.gov/ . NCT02441049 . Retrospectively
      registered 05.06.2015.

PMID- 30285756
TI  - Subtype-specific associations between breast cancer risk polymorphisms and the
      survival of early-stage breast cancer.
AB  - BACKGROUND: Limited evidence suggests that inherited predisposing risk variants
      might affect the disease outcome. In this study, we analyzed the effect of genome
      wide association studies-identified breast cancer-risk single nucleotide
      polymorphisms on survival of early-stage breast cancer patients in a Chinese
      population. METHODS: This retrospective study investigated the relationship
      between 21 GWAS-identified breast cancer-risk single nucleotide polymorphisms and
      the outcome of 1177 early stage breast cancer patients with a long median follow
      up time of 174 months. Cox proportional hazards regression models were used to
      estimate the hazard ratios and their 95% confidence intervals. Primary endpoints
      were breast cancer special survival and overall survival while secondary
      endpoints were invasive disease free survival and distant disease free survival.
      RESULTS: Multivariate survival analysis showed only the rs2046210 GA genotype
      significantly decreased the risk of recurrence and death for early stage breast
      cancer. After grouping breast cancer subtypes, significantly reduced survival was
      associated with the variant alleles of rs9485372 for luminal A and rs4415084 for
      triple negative breast cancer. Importantly, all three single-nucleotide
      polymorphisms, rs889312, rs4951011 and rs9485372 had remarkable effects on
      survival of luminal B EBC, either individually or synergistically. Furthermore,
      statistically significant multiplicative interactions were found between
      rs4415084 and age at diagnosis and between rs3803662 and tumor grade.
      CONCLUSIONS: Our results demonstrate that breast cancer risk susceptibility loci
      identified by GWAS may influence the outcome of early stage breast cancer
      patients' depending on intrinsic tumor subtypes in Chinese women.

PMID- 30285757
TI  - Role of maternity waiting homes in the reduction of maternal death and stillbirth
      in developing countries and its contribution for maternal death reduction in
      Ethiopia: a systematic review and meta-analysis.
AB  - BACKGROUND: Every family expect to have a healthy mother and new born baby after
      pregnancy. Especially for parents, pregnancy is a time of great anticipation.
      Access to maternal and child health care insures safer pregnancy and its outcome.
      MWHs is one the strategy. The objective was to synthesize the best available
      evidence on effectiveness of maternity waiting homes on the reduction of maternal
      mortality and stillbirth in developing countries. METHODS: Before conducting this
      review non-occurrences of the same review is verified. To avoid introduction of
      bias because of errors, two independent reviewers appraised each article.
      Maternal death and stillbirth were the primary outcomes. Review Manager 5 were
      used to produce a random-effect meta-analysis. Grade Pro software were used to
      produce risk of bias summary and summary of findings. RESULT: In developing
      countries, maternity waiting homes users were 80% less likely to die than non
      users (OR = 0. 20, 95% CI [0.08, 0.49]) and there was 73% less occurrence of
      stillbirth among users (OR = 0.27, 95% CI [0.09, 0.82]). In Ethiopia, there was a
      91% reduction of maternal death among maternity waiting homes users unlike non
      users (OR = 0.09, 95% CI [0.04, 0.19]) and it contributes to the reduction of 83%
      stillbirth unlike non-users (OR = 0.17, 95% CI [0.05, 0.58]). CONCLUSION:
      Maternity waiting home contributes more than 80% to the reduction of maternal
      death among users in developing countries and Ethiopia. Its contribution for
      reduction of stillbirth is good. More than 70% of stillbirth is reduced among the
      users of maternity waiting homes. In Ethiopia maternity waiting homes contributes
      to the reduction of more than two third of stillbirths.

PMID- 30285758
TI  - A longitudinal, multi-centre, superiority, randomized controlled trial of
      internet-based cognitive behavioural therapy (iCBT) versus treatment-as-usual
      (TAU) for negative experiences and posttraumatic stress following childbirth: the
      JUNO study protocol.
AB  - BACKGROUND: About one-third of women report their childbirth as traumatic and up
      to 10% have severe traumatic stress responses to birth. The prevalence of
      Posttraumatic stress disorder following childbirth (PTSD FC) is estimated to 3%.
      Women with PTSD FC report the same symptoms as other patients with PTSD following
      other types of trauma. The effect of psychological treatment for women with PTSD
      FC has only been studied in a few trials. Similarly, studies on treatment needs
      for women not diagnosed as having PTSD FC but who nevertheless face psychological
      problems are lacking. METHODS/DESIGN: Women who rate their overall birth
      experience as negative on a Likert scale, and/or had an immediate caesarean
      section and/or a major postpartum haemorrhage are randomized to either internet
      delivered cognitive behaviour therapy (iCBT) plus treatment as usual (TAU) or
      TAU. The iCBT is to be delivered in two steps. The first step consists of six
      weekly modules for both the woman and her partner (if they wish to participate)
      with minimal therapeutic support. Step 2 consists of eight weekly modules with
      extended therapeutic support and will be offered to participants whom after step
      1 report PTSD FC. Assessments will be made at baseline, 6 weeks, 14 weeks, and at
      follow-ups at 1, 2, 3 and 4 years after baseline. The primary outcome measures
      are symptoms of posttraumatic stress and depression. Secondary outcomes are
      quality of life, parent-child bonding, marital satisfaction, coping strategies,
      experience regarding the quality of care received, health-related quality of
      life, number of re-visits to the clinic and number of appointments for
      counselling during the 4 years' period after the negative childbirth experience,
      time until the woman gets pregnant again, and the type of birth in the subsequent
      pregnancy. A health economic evaluation in the form of a cost utility analysis
      will be conducted. DISCUSSION: This study protocol describes a randomized
      controlled trial that will provide information about the effectiveness of iCBT in
      women with negative experiences, posttraumatic stress, and PTSD FC. TRIAL
      REGISTRATION: ISRCTN39318241 . Date for registration 12/01/2017, retrospectively
      registered.

PMID- 30285760
TI  - Genomics of drug sensitivity in bladder cancer: an integrated resource for
      pharmacogenomic analysis in bladder cancer.
AB  - BACKGROUND: Bladder cancer has numerous genomic features that are potentially
      actionable by targeted agents. Nevertheless, both pre-clinical and clinical
      research using molecular targeted agents have been very limited in bladder
      cancer. RESULTS: We created the Genomics of Drug Sensitivity in Bladder Cancer
      (GDBC) database, an integrated database (DB) to facilitate the genomic
      understanding of bladder cancer in relation to drug sensitivity, in order to
      promote potential therapeutic applications of targeted agents in bladder cancer
      treatment. The GDBC database contains two separate datasets: 1) in-house drug
      sensitivity data, in which 13 targeted agents were tested against 10 bladder
      cancer cell lines; 2) data extracted and integrated from public databases,
      including the Cancer Therapeutics Research Portal, Cancer Cell Line Encyclopedia,
      Genomics of Drug Sensitivity in Cancer, Kyoto Encyclopedia of Genes and Genomes,
      and the Cancer Gene Census databases, as well as bladder cancer genomics data and
      synthetic lethality/synthetic dosage lethality connections. CONCLUSIONS: GDBC is
      an integrated DB of genomics and drug sensitivity data with a specific focus on
      bladder cancer. With a user-friendly web-interface, GDBC helps users generate
      genomics-based hypotheses that can be tested experimentally using drugs and cell
      lines included in GDBC.

PMID- 30285761
TI  - Case report: multiple UGT1A1 gene variants in a patient with Crigler-Najjar
      syndrome.
AB  - BACKGROUND: Inherited unconjugated hyperbilirubinemia is caused by variants in
      the gene UGT1A1 leading to Gilbert's syndrome and Crigler-Najjar syndrome types I
      and II. These syndromes are differentiated on the basis of UGT1A1 residual
      enzymatic activity and its affected bilirubin levels and responsiveness to
      phenobarbital treatment. CASE PRESENTATION: In this report, we present a boy with
      Crigler-Najjar syndrome type II with high unconjugated bilirubin levels that
      decreased after phenobarbital treatment but increased in adolescence. Four
      different UGT1A1 gene variants have been identified for this patient, of which
      one is novel (g.11895_11898del) most likely confirming diagnose molecularly.
      CONCLUSIONS: The presented case highlights the challenges encountered with the
      interpretation of molecular data upon identification of multiple variants in one
      gene that are causing different degree reducing effect on enzyme activity leading
      to several clinical conditions.

PMID- 30285759
TI  - Molecular characterization of three novel perforins in common carp (Cyprinus
      carpio L.) and their expression patterns during larvae ontogeny and in response
      to immune challenges.
AB  - BACKGROUND: In the host immune system, perforin is a cytotoxic effector molecule
      that eliminate virus-infected and malignant cells. Moreover, some recent studies
      also imply the involvement of perforin in antibacterial immunity. Common carp
      (Cyprinus carpio L.), one of the most economically important fish species in
      China, has a high susceptibility to viruses and bacteria. Thus far, in common
      carp, no data are available regarding the identification and immunologic function
      of the perforin. RESULTS: In the present study, the cDNA and genomic DNA
      sequences of three perforin isoform genes were cloned and characterized in common
      carp, named CcPRF1, CcPRF2 and CcPRF3. Amino acid sequences of the three CcPRFs
      were quite different, with identities ranged from 37.3 to 39.5%. Phylogenetic
      analysis showed that three CcPRFs, each in a separate sub-branch, possessed
      closer evolutionary relationship with other teleost perforins, especially with
      cyprinid fishes, than higher vertebrates. Expression analysis revealed that each
      CcPRF gene was differentially expressed in all of the nine tested tissues. During
      larvae ontogeny, each CcPRF displayed a distinct expression pattern, while with a
      common expression peak at 22 days post hatching (dph). Moreover, in vivo or in
      vitro, after stimulation with polyI:C, LPS and Aeromonas hydrophila, each CcPRF
      was induced significantly, with differential expression dynamics. CONCLUSIONS:
      Our findings suggest that perforin might play significant roles in larval immune
      system and in the immune defense of common carp against viral and bacterial
      pathogens. Meantime, the differential expression dynamics seem to imply possible
      different cellular locations or functional differences across various CcPRF
      isoforms.

PMID- 30285762
TI  - Echocardiographic markers of dyssynchrony as predictors of super-response to
      cardiac resynchronisation therapy - a pilot study.
AB  - BACKGROUND: Some patients with congestive heart failure have greater improvement
      of cardiac remodelling after cardiac resynchronisation therapy (CRT) and they are
      identified as super-responders (SRs). It remains unclear if echocardiographic
      markers of dyssynchrony could accuratelly predict super-response to CRT. The aim
      of this study is to evaluate potential echocardiographic predictors associated
      with super-response to CRT. METHODS: Fifthy nine CRT patients (mean age 52.9 +/-
      9.0 years, 88% men) with congestive heart failure (54% ischaemic and 46% non
      ischaemic aetiology) II-IV NYHA functional class were enrolled. To assess
      mechanical dyssynchrony we evaluated interventricular mechanical delay, the
      maximum delay between peak systolic velocities of the septal and posterior walls
      of left ventricle, duration of left ventricular pre-ejection period (LVPEP), left
      ventricular and interventricular dyssynchrony by tissue Doppler imaging and
      systolic dyssynchrony index by 3D echocardiography. After six months the patients
      were assessed for response and classified as SRs (reduction in left ventricular
      end-systolic volume (LVESV) >=30%, n = 20) and non-SRs (reduction in LVESV < 30%,
      n = 39) and baseline data were analyzed to identify the predictors. RESULTS: Both
      groups demonstrated significant improvement in NYHA functional class, increase in
      left ventricular ejection fraction and reduction in LVESV. All parameters of
      mechanical dyssynchrony at baseline were significantly higher in SR group.
      Multiple logistic regression analysis showed that LVPEP (HR 1.031; 95% CI 1.007
      1.055; p = 0.011) was an independent predictor for CRT super-response. In ROC
      curve analysis LVPEP with a cut-off value of 147 ms demonstrated 73.7%
      sensitivity and 75% specificity (AUC = 0.753; p = 0.002) for the prediction of
      super-response to CRT. CONCLUSION: Greater mechanical dyssynchrony is associated
      with super-response to CRT in patients with congestive heart failure. It is
      probable that an LVPEP > 147 ms can be used as independent predictor of super
      response.

PMID- 30285763
TI  - Engrailed-2 (EN2) - a novel biomarker in epithelial ovarian cancer.
AB  - BACKGROUND: Epithelial ovarian cancer is a common malignancy, with no clinically
      approved diagnostic biomarker. Engrailed-2 (EN2) is a homeodomain-containing
      transcription factor, essential during embryological neural development, which is
      dysregulated in several cancer types. We evaluated the expression of EN2 in
      Epithelial ovarian cancer, and reviewed its role as a biomarker. METHODS: We
      evaluated 8 Epithelial ovarian cancer cell lines, along with > 100 surgical
      specimens from the Royal Surrey County Hospital (2009-2014). In total, 108
      tumours and 5 normal tissue specimens were collected. En2 mRNA was evaluated by
      semi-quantitative RT-PCR. Histological sub-type, and platinum-sensitive/
      resistant status were compared. Protein expression was assessed in cell lines
      (immunofluorescence), and in > 150 tumours (immunohistochemistry). RESULTS: En2
      mRNA expression was elevated in serous ovarian tumours compared with normal ovary
      (p < 0.001), particularly in high-grade serous ovarian cancer (p < 0.0001) and in
      platinum-resistant tumours (p = 0.0232). Median Overall Survival and Progression
      free Survival were reduced with high En2 expression (OS = 28 vs 42 months, p =
      0.0329; PFS = 8 vs 27 months; p = 0.0004). Positive cytoplasmic EN2 staining was
      demonstrated in 78% of Epithelial ovarian cancers, with absence in normal ovary.
      EN2 positive high-grade serous ovarian cancer patients had a shorter PFS (10 vs
      17.5 months; p = 0.0103). CONCLUSION: The EN2 transcription factor is a novel
      ovarian cancer biomarker. It demonstrates prognostic value, correlating with
      worse Overall Survival and Progression-free Survival. It is hoped that further
      work will validate its use as a biomarker, and provide insight into the role of
      EN2 in the development, progression and spread of ovarian cancer.

PMID- 30285764
TI  - Reduced menin expression impairs rapamycin effects as evidenced by an increase in
      mTORC2 signaling and cell migration.
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR) is a master regulator of various
      cellular responses by forming two functional complexes, mTORC1 and mTORC2. mTOR
      signaling is frequently dysregulated in pancreatic neuroendocrine tumors (PNETs).
      mTOR inhibitors have been used in attempts to treat these lesions, and prolonged
      progression free survival has been recorded. If this holds true also for the
      multiple endocrine neoplasia type 1 (MEN1) associated PNETs is yet unclear. We
      investigated the relationship between expression of the MEN1 protein menin and
      mTOR signaling in the presence or absence of the mTOR inhibitor rapamycin.
      METHODS: In addition to use of menin wild type and menin-null mouse embryonic
      fibroblasts (MEFs), menin was silenced by siRNA in pancreatic neuroendocrine
      tumor cell line BON-1. Panels of protein phosphorylation, as activation markers
      downstream of PI3k-mTOR-Akt pathways, as well as menin expression were evaluated
      by immunoblotting. The impact of menin expression in the presence and absence of
      rapamycin was determinate upon Wound healing, migration and proliferation in MEFs
      and BON1 cells. RESULTS: PDGF-BB markedly increased phosphorylation of mTORC2
      substrate Akt, at serine 473 (S473) and threonine 450 (T450) in menin-/- MEFs but
      did not alter phosphorylation of mTORC1 substrates ribosomal protein S6 or eIF4B.
      Acute rapamycin treatment by mTORC1-S6 inhibition caused a greater enhancement of
      Akt phosphorylation on S473 in menin-/- cells as compared to menin+/+ MEFs (116%
      vs 38%). Chronic rapamycin treatment, which inhibits both mTORC1and 2, reduced
      Akt phosphorylation of S473 to a lesser extent in menin-/- MEFs than menin+/+
      MEFs (25% vs 75%). Silencing of menin expression in human PNET cell line (BON1)
      also enhanced Akt phosphorylation at S473, but not activation of mTORC1.
      Interestingly, silencing menin in BON1 cells elevated S473 phosphorylation of Akt
      in both acute and chronic treatments with rapamycin. Finally, we show that the
      inhibitory effect of rapamycin on serum mediated wound healing and cell migration
      is impaired in menin-/- MEFs, as well as in menin-silenced BON1 cells.
      CONCLUSIONS: Menin is involved in regulatory mechanism between the two mTOR
      complexes, and its reduced expression is accompanied with increased mTORC2-Akt
      signaling, which consequently impairs anti-migratory effect of rapamycin.

PMID- 30285765
TI  - Combining multi-scale composite windows with hierarchical smoothing strategy for
      fingerprint orientation field computation.
AB  - BACKGROUND: Orientation field (OF) plays a very significant role in automatic
      fingerprint recognition systems. Many algorithms have been proposed for the
      estimation of fingerprints' OF but it is hard to solve the dilemma of correcting
      spurious ridge structure and avoiding singularity location deviation, especially
      for poor images. So far, the following drawbacks still need to be solved for OF
      construction methods for practical application: (1) How to adaptively choose
      block scales to resolve the contradiction between accuracy and anti-noise, since
      small scale is beneficial to accuracy but is sensitive to noise, while large
      scale is more resistant to noise, but the accuracy is deteriorated. (2) How to
      construct the genuine OF in the areas close-by singular points and to evade
      singularity location deviation? Current block based methods give spurious OF
      estimates in the area near singular points because these areas have large
      curvature thus the detected singular points deviate from the genuine
      localizations. When these singular points are used as the anchor for referencing
      minutiae, it makes the average error of matching or recognition even larger.
      Therefore, it is essentials to construct the genuine OF in the areas close-by
      singular points and to evade singularity deviation. METHODS: To overcome the
      above-mentioned limitations, a novel method, combining a weighted multi-scale
      composite window (WMCM) with a hierarchical smoothing strategy has been proposed
      for the computation of fingerprint OF. This method mainly contains two
      procedures: the approximate OF estimation and the hierarchical OF smoothing. In
      the first procedure, a series of OFs are established under multiple scales of
      composite windows by using a gradient based method then a coarse OF is estimated
      using the weight of each scale determined by a squared gradient consistency. In
      the second procedure, the OF is first quantized into a two-digitized orientation
      zone and a two-orientation-zone filtering strategy is adapted to the OF blocks
      based on a filtering mask obtained after eliminating the isolated blocks. In the
      end a similar three-digitized orientation zone is performed to obtain an accurate
      and smooth OF. To validate the performance, the proposed method has been applied
      to OF computation using the FVC2004 databases and three experiments are designed.
      Experiment 1 aims to validate whether the weighted multi-scale composite window
      can balance the dilemma of accuracy and robustness more effectively than the
      previous works do. Experiment 2 is designed to examine whether the hierarchical
      smoothing method can correct the spurious ridge flow and preserve the genuine
      localization of singular points. The purpose of experiment 3 is to test the
      performance of the proposed method on OF reconstruction in low quality
      fingerprint images. The fingerprint databases FVC 2004 DB1-DB4 are employed in
      this study. RESULTS: The results of experiment I shows that the proposed method
      is capable to extract the information of OF reliably and it is more robust
      against singularity localization deviation in comparison with the other three
      gradient based methods. The results of experiment II indicates that the proposed
      smoothing method can balance the contradiction in correcting spurious ridge
      structures and preserving genuine singularity localization. The results of
      experiment III illustrates that our approach combing WMCW with the hierarchical
      smoothing method is capable to extract the information of OF ridge reliably and
      it is more robust against singularity deviation in comparison with the other
      three gradient based methods. In a word, the experiment results demonstrate that
      the proposed method can correct spurious ridge structure and meanwhile avoid
      singularity deviation compared with the previous works. CONCLUSIONS: A novel
      gradient based algorithm has been proposed which is more reliable for the
      estimation of the ridge information for fingerprint OF and is more accurate in
      preserving the singularity localization. Compared with the previously proposed
      gradient based methods, the advantages of the proposed RBSF lie in three aspects.
      Firstly a weighted multi-scale composite window is put forward to replace the
      single window used by conventional gradient based methods and to adaptively
      choose the scales of the blocks. Secondly, a hierarchical smoothing strategy is
      proposed to enhance the OF by using the two-orientation-zone filtering and the
      three-orientation-zone filtering, aiming to correct the spurious ridges and
      preserving the genuine location of singular points. Finally, three experiments
      are designed to test the proposed algorithm together with other popular gradient
      based methods on real fingerprint images, which are selected from different
      categories and all are suffering from obvious noise effects. All the experiment
      results show that the proposed method is superior with respect to reliable OF
      construction and avoiding singularity localization deviation.

PMID- 30285766
TI  - Conceptualising production, productivity and technology in pharmacy practice: a
      novel framework for policy, education and research.
AB  - CONTEXT AND BACKGROUND: People and health systems worldwide face serious
      challenges due to shifting disease demographics, rising population demands and
      weaknesses in healthcare provision, including capacity shortages and lack of
      impact of healthcare services. These multiple challenges, linked with the global
      push to achieve universal health coverage, have made apparent the importance of
      investing in workforce development to improve population health and economic well
      being. In relation to medicines, health systems face challenges in terms of
      access to needed medicines, optimising medicines use and reducing risk. In 2017,
      the International Pharmaceutical Federation (FIP) published global policy on
      workforce development ('the Nanjing Statements') that describe an envisioned
      future for professional education and training. The documents make clear that
      expanding the pharmacy workforce benefits patients, and continually improving
      education and training produces better clinical outcomes. AIMS AND PURPOSE: The
      opportunities for harnessing new technologies in pharmacy practice have been
      relatively ignored. This paper presents a conceptual framework for analysing
      production methods, productivity and technology in pharmacy practice that
      differentiates between dispensing and pharmaceutical care services. We outline a
      framework that may be employed to study the relationship between pharmacy
      practice and productivity, shaped by educational and technological inputs. METHOD
      AND RESULTS: The analysis is performed from the point of view of health systems
      economics. In relation to pharmaceutical care (patient-oriented practice),
      pharmacists are service providers; however, their primary purpose is not to
      deliver consultations, but to maximise the quantum of health gain they secure.
      Our analysis demonstrates that 'technology shock' is clearly beneficial compared
      with orthodox notions of productivity or incremental gain implementations.
      Additionally, the whole process of providing professional services using
      'pharmaceutical care technologies' is governed by local institutional frames,
      suggesting that activities may be structured differently in different places and
      countries. DISCUSSION AND CONCLUSION: Addressing problems with medication use
      with the development of a pharmaceutical workforce that is sufficient in quantity
      and competence is a long-term issue. As a result of this analysis, there emerges
      a challenge about the profession's relationship with existing and emerging
      technical innovations. Our novel framework is designed to facilitate policy,
      education and research by providing an analytical approach to service delivery.
      By using this approach, the profession could develop examples of good practice in
      both developed and developing countries worldwide.

PMID- 30285767
TI  - Rasch analysis of the Herth Hope Index in cancer patients.
AB  - BACKGROUND: The concept of hope has been measured using the Herth Hope Index
      (HHI) in different samples, but varying factor structures comprising different
      items from the HHI have been reported. Therefore, further testing with regard to
      the dimensionality of the instrument is recommended. Rasch modeling can be used
      to evaluate validity evidence of an instrument's underlying structure, to
      identify items with poor fit to the rest of the scale, and to identify items that
      perform inconsistently across groups. The aim of this study was to assess the
      HHI's psychometric properties in a sample of cancer patients using a Rasch model.
      Adult oncology outpatients (n = 167) with pain from bone metastasis were
      included, and medical records were reviewed for disease and treatment
      information. Patients completed the 12-item HHI, which measures various
      dimensions of hope using a 4-point Likert scale that ranges from 1 (strongly
      disagree) to 4 (strongly agree). The internal scale validity, person response
      validity, unidimensionality, and uniform differential item functioning were
      evaluated by applying a Rasch rating scale model. RESULTS: Five (42%) of the
      twelve items (#3, #4, #5, #6 and #7) did not meet the criterion set for item
      goodness-of-fit. After removing these 5 items, the resulting 7-item scale
      demonstrated acceptable item fit to the model, acceptable unidimensionality
      (52.6% of the variance explained), acceptable person goodness-of-fit, adequate
      separation, and no differential item function. CONCLUSION: A 7-item version of
      the HHI had better psychometric properties than the original 12-item version
      among patients with cancer-related pain. TRIAL REGISTRATION: The protocol ID is
      158,707/V10 and it was registered on ClinicalTrials.gov as NCT00760305 .
      Registered September 25, 2008.

PMID- 30285768
TI  - Decision-making preceding induced abortion: a qualitative study of women's
      experiences in Kisumu, Kenya.
AB  - BACKGROUND: Unwanted pregnancies and unsafe abortions are prevalent in regions
      where women and adolescent girls have unmet contraceptive needs. Globally, about
      25 million unsafe abortions take place every year. In countries with restrictive
      abortion laws, safe abortion care is not always accessible. In Kenya, the high
      unwanted pregnancy rate resulting in unsafe abortions is a serious public health
      issue. Gaps exist in knowledge regarding women's decision-making processes in
      relation to induced abortions in Kenya. Decision-making is a fundamental factor
      for consideration when planning and implementing contraceptive services. This
      study explored decision-making processes preceding induced abortion among women
      with unwanted pregnancy in Kisumu, Kenya. METHODS: Individual face-to-face in
      depth interviews were conducted with nine women aged 19-32 years old. Women who
      had experienced induced abortion were recruited after receiving post-abortion
      care at the Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) or
      Kisumu East District Hospital (KDH) in Kisumu, Kenya. In total, 15 in-depth
      interviews using open-ended questions were conducted. All interviews were tape
      recorded, transcribed and coded manually using inductive content analysis.
      RESULTS: Respondents described their own experiences regarding decision-making
      preceding induced abortion. This study shows that the main reasons for induced
      abortion were socio-economic stress and a lack of support from the male partner.
      In addition, deviance from family expectations and gender-based norms highly
      influenced the decision to have an abortion among the interviewed women. The
      principal decision maker was often the male partner who pressed for the
      termination of the pregnancy indirectly by declining his financial or social
      responsibilities or directly by demanding termination. In some cases, the male
      partner controlled decision-making by arranging an unsafe abortion without the
      woman's consent. Strategic choices regarding whom to confide in were employed as
      protection against abortion stigma. This contributed to a culture of silence
      around abortion and unwanted pregnancy, a factor that made women more vulnerable
      to complications. CONCLUSIONS: The findings suggest that financial, social and
      gender-based dependencies influence women's agency and perceived options in
      decision-making regarding abortion.

PMID- 30285770
TI  - Efficacy of anti-PD-1/PD-L1 antibodies after discontinuation due to adverse
      events in non-small cell lung cancer patients (HANSHIN 0316).
AB  - BACKGROUND: Immune checkpoint inhibitors (ICIs) have emerged as promising
      therapeutic agents in non-small cell lung cancer (NSCLC). However, the duration
      for which ICIs should be continued remains a clinical problem. METHODS: We
      examined the efficacy of anti-PD-1/PD-L1 inhibitors after the discontinuation of
      antibodies due to adverse events (AEs) in patients with NSCLC. This was a
      multicenter retrospective study that analyzed NSCLC patients who were treated
      with PD-1/PD-L1 inhibitors by August 2016. RESULTS: The patients with NSCLC were
      18 males and 1 female at a median 67 years of age (range: 49-80 years). Eighteen
      of 19 patients were treated with nivolumab, one was with atezolizumab.
      Approximately half of AEs were interstitial pneumonia. Fourteen patients (73.7%)
      were treated with steroid therapy. The median number of treatment cycles was 7
      (range, 1-70), and the median duration of treatment was 2.8 months (range, 1 day
      32.9 months). The overall response rate with confirmation during treatment was
      21.1%. The median progression-free survival (PFS) was 10.2 months (95% confidence
      interval [CI] = 3.2-17.1 months) and 5.6 months (95% CI = 0-12.2 months) from the
      initiation and the discontinuation of PD-1/PD-L1 treatment, respectively. The
      median PFS after discontinuation according to the confirmed response during
      administration was not reached for partial response (PR) and 4.9 months (95% CI,
      3.7-6.0) for stable disease (SD) patients (P = 0.02). CONCLUSION: The PFS of the
      PR patients was completely different from that of the SD patients. The cases with
      PR prior to the onset of AE tended to show a durable response after the
      discontinuation of PD-1/PD-L1 inhibitors.

PMID- 30285769
TI  - Adeno-associated virus gene delivery of broadly neutralizing antibodies as
      prevention and therapy against HIV-1.
AB  - Vectored gene delivery of HIV-1 broadly neutralizing antibodies (bNAbs) using
      recombinant adeno-associated virus (rAAV) is a promising alternative to
      conventional vaccines for preventing new HIV-1 infections and for therapeutically
      suppressing established HIV-1 infections. Passive infusion of single bNAbs has
      already shown promise in initial clinical trials to temporarily decrease HIV-1
      load in viremic patients, and to delay viral rebound from latent reservoirs in
      suppressed patients during analytical treatment interruptions of antiretroviral
      therapy. Long-term, continuous, systemic expression of such bNAbs could be
      achieved with a single injection of rAAV encoding antibody genes into muscle
      tissue, which would bypass the challenges of eliciting such bNAbs through
      traditional vaccination in naive patients, and of life-long repeated passive
      transfers of such biologics for therapy. rAAV delivery of single bNAbs has
      already demonstrated protection from repeated HIV-1 vaginal challenge in
      humanized mouse models, and phase I clinical trials of this approach are
      underway. Selection of which individual, or combination of, bNAbs to deliver to
      counter pre-existing resistance and the rise of escape mutations in the virus
      remains a challenge, and such choices may differ depending on use of this
      technology for prevention versus therapy.

PMID- 30285771
TI  - Exosome-transmitted long non-coding RNA PTENP1 suppresses bladder cancer
      progression.
AB  - BACKGROUND: Extracellular communication within the tumor microenvironment plays a
      critical role in tumor progression. Although exosomes can package into long non
      coding RNAs (lncRNAs) to mediate extracellular communication, the role of
      exosomal lncRNA PTENP1 in bladder cancer (BC) remains unclear. METHOD: We
      detected PTENP1 expression between patients with BC and healthy controls; the
      expression occurred in tissues and exosomes from plasma. We assessed the
      diagnostic accuracy by the receiver operating characteristic curve (ROC) and the
      area under curve (AUC). Cell phenotypes and animal experiments were performed to
      determine the effect of exosomal PTENP1. RESULTS: PTENP1 was significantly
      reduced in BC tissues and in exosomes from plasma of patients with BC (P < 0.05).
      We found that PTENP1 was mainly wrapped by exosomes. Exosomal PTENP1 could
      distinguish patients with BC from healthy controls (AUC = 0.743; 95% confidence
      interval (CI) = 0.645-0.840). Normal cells secreted exosomal PTENP1 and
      transmitted it to BC cells, thus inhibiting the biological malignant behavior of
      BC cells by increasing cell apoptosis and reducing the ability to invade and
      migrate (P < 0.05). Exosomal PTENP1 could suppress tumor growth in vivo.
      Furthermore, exosomal PTENP1 mediated the expression of PTEN by competitively
      binding to microRNA-17. CONCLUSION: Exosomal PTENP1 is a promising novel
      biomarker that can be used for the clinical detection of BC. Exosomes derived
      from normal cells transfer PTENP1 to BC cells, which reduce the progression of BC
      both in vitro and in vivo and suggest that exosomal PTENP1 participates in normal
      cell-to-bladder-cell communication during the carcinogenesis of BC.

PMID- 30285772
TI  - Availability of adequately iodized salt at household level in Dessie and
      Combolcha Towns, South Wollo, Ethiopia.
AB  - BACKGROUND: Iodine deficiency disorder is the leading cause of mental retardation
      and poor economic performance in developing countries. Worldwide, universal salt
      iodization has been implemented to eliminate iodine deficiency. However, the
      adequacy of iodine in salts needs close monitoring to meet its intended goal and
      this study was aimed at investigating the adequacy of iodine in dietary salt at
      household level in Dessie and Combolcha Towns. METHODS: A community-based cross
      sectional study was employed at household level in Dessie and Combolcha towns
      from January to February, 2017. Data were collected from 753 households using
      systematic sampling technique. The adequacy of iodine in salt was analyzed using
      rapid testing kit. Socio-demographic and economic, dietary sources, labeling,
      packaging, storage and cooking methods of household's characteristics were
      collected via questionnaire developed using open data kit tool and STATA version
      12 was used for further statistical analysis. Ordinal Logistic regression was
      performed to assess associations between explanatory variables and the response
      variable. RESULTS: Nearly one-thrid (31.2%) of the households used inadequate
      iodized salt, which was below the World Health Organization recommendation level
      (>=15 ppm at the household level). Most of the respondents from Combolcha town
      (64.6%) were affected by inadequate use of iodized salt as compared to Dessie
      Town residents (22.2%). Being Dessie resident (OR = 2.53; 95% CI: 1.31-4.90),
      households with better socioeconomic status (OR = 2.54; 95% CI:1.10-5.87), site
      of labeling and packing (salt from open market (OR = 0.10; 95% CI: 0.04-0.23) and
      no exposure to sunlight (OR = 2.54; 95% CI:1.31-4.91) were the predictors of
      adequacy of iodized salt at household level. CONCLUSIONS: Availability of
      adequately iodized salt at the household level in the study area was low. There
      should be regular quality control and regulatory enforcement of salt iodization
      at production, labeling and packaging sites of small scale industries and at
      household level.

PMID- 30285775
TI  - Hospitalization for mental health related ambulatory care sensitive conditions:
      what are the trends for First Nations in British Columbia?
AB  - BACKGROUND: Indigenous peoples globally experience a disproportionate burden of
      mental illness due to forced policies and practices of colonization and cultural
      disruption. The objective of this study was to provide a baseline profile of
      hospitalization rates for mental health-related Ambulatory Care Sensitive
      Conditions among First-Nations living both on and off reserve in British
      Columbia, Canada, and explore the relationship between local access to health
      services and mental health-related hospitalization rates. METHODS: A population
      based time trend analysis of mental health-related Ambulatory Care Sensitive
      Conditions hospitalizations was conducted using de-identified administrative
      health data. The study population included all residents eligible under the
      universal British Columbia Medical Services Plan and living on and off First
      Nations reserves between 1994/95 and 2009/10. The definition of mental health
      related Ambulatory Care Sensitive Conditions included mood disorders and
      schizophrenia, and three different change measures were used to operationalize
      avoidable hospitalizations: 1) rates of episodes of hospital care, 2) rates of
      length of stay, and 3) readmission rates. Data were analyzed using generalized
      estimating equations approach, controlling for age, sex, and socio-economic
      status, to account for change over time. RESULTS: Our findings show that First
      Nations living on reserve have higher hospitalization rates for mental disorders
      compared to other British Columbia residents up until 2008. Those living off
      reserve had significantly higher hospitalization rates throughout the study
      period. On-reserve communities served by nursing stations had the lowest rates of
      hospitalization whereas communities with limited local services had the highest
      rates. Compared to other British Columbia residents, all First Nations have a
      shorter length of stay and lower readmission rates. CONCLUSIONS: This study
      suggests that despite reduced rates of hospitalization for mental-health related
      Ambulatory Care Sensitive Conditions over time for First Nations, gaps in mental
      health care still exist. We argue greater investments in primary mental health
      care are needed to support First Nations health. However, these efforts should
      place equal importance on prevention and the social determinants of health.

PMID- 30285774
TI  - The new clinical standard of integrated quadruple stress echocardiography with
      ABCD protocol.
AB  - BACKGROUND: The detection of regional wall motion abnormalities is the
      cornerstone of stress echocardiography. Today, stress echo shows increasing
      trends of utilization due to growing concerns for radiation risk, higher cost and
      stronger environmental impact of competing techniques. However, it has also
      limitations: underused ability to identify factors of clinical vulnerability
      outside coronary artery stenosis; operator-dependence; low positivity rate in
      contemporary populations; intermediate risk associated with a negative test;
      limited value of wall motion beyond coronary artery disease. Nevertheless, stress
      echo has potential to adapt to a changing environment and overcome its current
      limitations. INTEGRATED-QUADRUPLE STRESS-ECHO: Four parameters now converge
      conceptually, logistically, and methodologically in the Integrated Quadruple (IQ)
      stress echo. They are: 1- regional wall motion abnormalities; 2-B-lines measured
      by lung ultrasound; 3-left ventricular contractile reserve assessed as the
      stress/rest ratio of force (systolic arterial pressure by cuff
      sphygmomanometer/end-systolic volume from 2D); 4- coronary flow velocity reserve
      on left anterior descending coronary artery (with color-Doppler guided pulsed
      wave Doppler). IQ-Stress echo allows a synoptic functional assessment of
      epicardial coronary artery stenosis (wall motion), lung water (B-lines),
      myocardial function (left ventricular contractile reserve) and coronary small
      vessels (coronary flow velocity reserve in mid or distal left anterior descending
      artery). In "ABCD" protocol, A stands for Asynergy (ischemic vs non-ischemic
      heart); B for B-lines (wet vs dry lung); C for Contractile reserve (weak vs
      strong heart); D for Doppler flowmetry (warm vs cold heart, since the hyperemic
      blood flow increases the local temperature of the myocardium). From the technical
      (acquisition/analysis) viewpoint and required training, B-lines are the
      kindergarten, left ventricular contractile reserve the primary (for acquisition)
      and secondary (for analysis) school, wall motion the university, and coronary
      flow velocity reserve the PhD program of stress echo. CONCLUSION: Stress echo is
      changing. As an old landline telephone with only one function, yesterday stress
      echo used one sign (regional wall motion abnormalities) for one patient with
      coronary artery disease. As a versatile smart-phone with multiple applications,
      stress echo today uses many signs for different pathophysiological and clinical
      targets. Large scale effectiveness studies are now in progress in the Stress
      Echo2020 project with the omnivorous "ABCD" protocol.

PMID- 30285777
TI  - Intravesical migration of female urethral dilator: a case report of a new
      urologic emergency in the era of e-commerce.
AB  - BACKGROUND: The introduction of foreign bodies in the female urethra for auto
      erotic stimulation or in case of psychiatric disorders is not uncommon. The
      occurrence of intravesical migration of these objects makes it necessary to
      remove it shortly after insertion, since after long term permanence complications
      are likely to occurr. CASE PRESENTATION: A 47-year-old white female was referred
      at our Urology department for migration inside the bladder of a metallic urethral
      dilator used for sexual stimulation. An ultrasound study and an X-ray plate of
      the pelvis clearly visualized the presence of an object shaped like a rifle
      bullet located in the bladder. Twenty-four hours later, the patient reported its
      spontaneous emission through the urethra during micturition. This was confirmed
      by US and X-ray imaging. CONCLUSIONS: The retrieval of foreign objects introduced
      through body orifices with purpose of sexual gratification is a known urological
      expertise. Curiously, in the case reported, the patient was able to manipulate
      the object thus facilitating its correct orientation and passage outside the
      bladder during micturition. To the best of our knowledge this is the first case
      of documented spontaneous emission through the urethra of a sizable intravesical
      foreign body. Sexual gratification in females though the insertion of urethral
      dilators is a growing practice, as demonstrated by the broad proposal of such
      instruments on the web. Therefore, the occurrence of accidental intravesical
      displacement of such kind of foreign body is increasingly likely, and the
      Urologists must be aware of this possibility.

PMID- 30285776
TI  - Cell adhesion-related gene somatic mutations are enriched in aggressive papillary
      thyroid microcarcinomas.
AB  - BACKGROUND: Approximately half of the documented increases in differentiated
      thyroid carcinoma is due to identification of papillary thyroid microcarcinomas
      (PTMCs). Knowing whether PTMC is aggressive is required for proper treatment, but
      until now, there has been no method for assessing these traits and understanding
      the underlying mechanisms for aggressiveness. METHODS: We performed whole-exome
      sequencing of 16 PTMCs and matched normal thyroid tissues and GO/KEGG analysis to
      study genetic alterations and biological consequences associated with aggressive
      PTMCs, and then sequenced these genes using a next-generation gene-panel approach
      in an additional 70 PTMC samples including aggressive (n = 50) and non-aggressive
      (n = 20) groups. RESULTS: We identified 254 somatic mutations of 234 genes, for
      which 178 mutations in 168 genes were found in the aggressive group, and 76
      mutations in 74 genes were found in the non-aggressive group. Several recurrent
      mutations in BRAF, VCAN, ALDH1L1, and MUC5B were identified, and many novel but
      infrequent mutations in other genes were also found. The aggressive cohort had
      more mutational burdens than the non-aggressive group (P = 0.004). Nonsynonymous
      mutations of 13 genes (MUC5B, TNN, SSPO, PPFIA1, PCDHGA2, ITGA8, ITGA4, DCHS1,
      CRNN, ROCK1, RELN, LAMC2, and AEBP1) were involved in cell adhesion, and these
      were only present in the aggressive group. Targeted sequencing of these genes
      revealed significant enrichment in the aggressive group (P = 0.000004).
      CONCLUSION: PTC may have evolved from PTMC due to sharing similar gene mutations,
      and the accumulation of such mutations promoted the aggressiveness of PTMC. Gene
      mutants associated with cell adhesion may be used to predict PTMC aggressiveness
      and allow more selective treatment.

PMID- 30285773
TI  - Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome
      (ME/CFS).
AB  - BACKGROUND AND MAIN TEXT: Myalgic encephalomyelitis/chronic fatigue syndrome
      (ME/CFS) is a complex and controversial clinical condition without having
      established causative factors. Increasing numbers of cases during past decade
      have created awareness among patients as well as healthcare professionals.
      Chronic viral infection as a cause of ME/CFS has long been debated. However, lack
      of large studies involving well-designed patient groups and validated
      experimental set ups have hindered our knowledge about this disease. Moreover,
      recent developments regarding molecular mechanism of pathogenesis of various
      infectious agents cast doubts over validity of several of the past studies.
      CONCLUSIONS: This review aims to compile all the studies done so far to
      investigate various viral agents that could be associated with ME/CFS.
      Furthermore, we suggest strategies to better design future studies on the role of
      viral infections in ME/CFS.

PMID- 30285778
TI  - Molecular characterization of human adenovirus associated with acute respiratory
      infections in Cameroon from 2011 to 2014.
AB  - BACKGROUND: Human adenoviruses (HAdVs) cause a wide range of diseases worldwide,
      including respiratory infections. Studies on HAdV molecular epidemiology are
      limited in Cameroon. The purpose of this study is to document the different types
      HAdV circulating in Cameroon in children with acute respiratory infections.
      METHODS: Nasopharyngeal swabs were collected from 811 children under 15 years
      from 2011 to 2014. The HAdV detection was assessed by semi-quantitative generic
      PCR r-gene(r). The HAdV-positive samples were typed by amplification and
      sequencing of partial hexon gene and a real-time PCR. Demographic data were
      collected and analyzed. The infection and hospitalization risk factors were
      assessed thought the Chi-square test. RESULTS: A total of 137/220 HAdV-positive
      samples were amplified successfully. Six species of HAdV (Mastadenovirus A to F)
      were detected with B (108/220) and C (47/220) being the predominant strains.
      Hospitalization and age were significantly associated to HAdV-B and HAdV-C
      respectively. Phylogenetic analysis of HAdV-B3 virus (18) and B7 (5) shows a
      conserved and a significant temporal stability in relation to the reference
      sequence (99.1 to 100% of similarity). CONCLUSION: This study reported HAdV
      species and types detected in children with acute respiratory infections in
      Cameroon between September 2011 and July 2014. These results support further
      evaluation of the spatio-temporal circulation pattern of HAdV species and types
      in Cameroon.

PMID- 30285779
TI  - Ugandan providers' views on the acceptability of contraceptive self-injection for
      adolescents: a qualitative study.
AB  - BACKGROUND: Self-injection of subcutaneous depot medroxyprogesterone acetate may
      offer greater discretion and increase access to injectable contraception,
      particularly for those who face challenges accessing clinic services. In
      particular, unmarried adolescents often encounter stigma when seeking services,
      and may also lack the financial means to travel to clinics on the quarterly basis
      that injectable contraception requires. Whether self-injection is offered to
      women on a wide scale basis, and to adolescents specifically, will depend in part
      upon the willingness of providers to train clients of diverse ages and
      educational backgrounds. This study explores the views of providers with regard
      to self-injection as an option for women and adolescents in Uganda. METHODS: In
      depth qualitative interviews were conducted with family planning providers in
      Gulu district, to understand their views on injectable self-injection for women,
      with a specific focus on unmarried adolescents ages 15 to 19 years. The in-depth
      interviews, which lasted up to 60 min were audio-recorded, translated and
      transcribed simultaneously, and analyzed using Atlas.ti software to identify key
      themes and common perspectives. RESULTS: A total of 40 health care providers were
      interviewed with equal numbers of each type (public, NGO, and private clinics,
      pharmacies, and community-based health workers). While most providers were
      receptive to self-injection for adult women, fewer than half were supportive of
      adolescent self-injection. Their reservations focused on age, marital status and
      parity concerns around adolescent use of the injectable more broadly, and
      concerns about the ability of adolescents to self-inject safely. CONCLUSIONS:
      Self-injection presents an opportunity to reduce the enormous burden on the
      public sector health system in Uganda, which is particularly compounded by the
      heavy reliance on injectable contraception requiring quarterly clinic visits. The
      results of this study reveal a level of cautious support for self-injection among
      providers when it comes to self-injection by adult women. With respect to
      adolescent clients, family planning policymakers and program implementers should
      design, implement, and evaluate self-injection interventions with the needs of
      adolescent clients uppermost in mind, recognizing that extra attention will
      likely be needed to reduce provider-imposed restrictions on adolescent access to
      this injectable delivery modality.

PMID- 30285780
TI  - Robotic versus laparoscopic surgery for rectal cancer in male urogenital function
      preservation, a meta-analysis.
AB  - BACKGROUND: Urogenital dysfunction after rectal cancer surgery can largely affect
      patients' postoperative quality of life. Whether robotic surgery can be a better
      option when comparing with laparoscopic surgery is still not well-known. METHODS:
      Comprehensive search in PubMed, Embase, Cochrane Library, and Clinical Trials was
      conducted to identify relevant studies in March 2018. Studies comparing robotic
      surgery with laparoscopic surgery were included. Measurement of urogenital
      function was through the International Prostate Symptom Score and International
      Index of Erectile Function. RESULTS: Six studies with 386 patients in robotic
      group and 421 patients in laparoscopic group were finally included. Pooled
      analysis indicated that bladder function was better at 12 months in the robotic
      group after the procedures (mean difference, - 0.30, 95% CI, - 0.52 to - 0.08).
      No significant difference was found at 3 and 6 months postoperatively (mean
      difference, - 0.37, 95% CI, - 1.48 to 0.73; mean difference, - 1.21, 95% CI, -
      2.69 to 0.28). Sexual function was better at 3 months in the robotic group after
      surgery (mean difference, - 3.28, 95% CI, - 6.08 to - 0.49) and not significantly
      different at 6 and 12 months. (mean difference, 3.78, 95% CI, - 7.37 to 14.93;
      mean difference, - 2.82, 95% CI, - 8.43 to 2.80). CONCLUSION: Robotic surgery may
      offer faster recovery in urogenital function compared to laparoscopic surgery for
      rectal cancer.

PMID- 30285781
TI  - Molecular pathological expression in malignant gliomas resected by fluorescein
      sodium-guiding under the YELLOW 560 nm surgical microscope filter.
AB  - BACKGROUND: This study aimed to analyze the relationship between molecular
      pathologic expression of GFAP and Ki-67 and fluorescence levels, and to provide
      molecular pathological basis for the removal of malignant gliomas (MG) by
      Fluorescein Sodium (FLS) navigation under the YELLOW 560 nm surgical microscope
      filter. METHODS: A retrospective analysis of clinical data of 18 MG cases
      confirmed by the postoperative pathology was performed. All cases were resected
      by FLS guiding under the YELLOW 560 nm filter. Hematoxylin-eosin (HE) staining,
      molecular pathology markers GFAP, and Ki-67 immunohistochemical staining of the
      specimens were performed. The relationship between fluorescence staining levels
      and GFAP positive rate, Ki-67 proliferation index, and WHO grades was studied.
      RESULTS: There were 69 pathological specimens with fluorescence levels of
      "bright" fluorescence (n = 32), "low" fluorescence (n = 18), and "no"
      fluorescence (n = 19). Immunohistochemical staining showed GFAP-positive
      expression in both tumor cells and normal glial cells. The staining levels of the
      specimens in the fluorescence regions were higher than that in the non
      fluorescence regions. GFAP expression was positive in 61 specimens and negative
      in 8 specimens. Comparison of Ki-67 proliferation index using chi-square test
      showed different fluorescence levels had different Ki-67 proliferation indexes
      (chi2 = 14.678, p = 0.005). With high proliferation index of specimens,
      fluorescence level was brighter. WHO grade had no correlation with fluorescence
      levels (chi2 = 3.531, p = 0.171). CONCLUSION: FLS-guided resection of MG is safe
      and effective. In the boundary area of MG, fluorescence levels and Ki-67
      proliferation index showed correlation. FLS-guided resection achieved the
      function of "reducing tumor cell," thus reducing the proliferation index in the
      lesion area.

PMID- 30285782
TI  - Overview of literature on RMC and applications to Tanzania.
AB  - Respectful maternity care research in Tanzania continues to increase. This is an
      overview of the literature summarizing research based on the domains which
      comprise this quality of care indicator, ranging from exploratory and descriptive
      to quantitative measurements of birth perinatal outcomes when respectful
      interventions are made. The domains of respectful care are reflected in the seven
      Universal Rights of Childbearing Women but go further to implicate facility
      administrators and policy makers to provide supportive infrastructure to allay
      disrespect and abuse.The research methodologies continue to be problematic and
      several ethical cautions restrict how much control is possible. Similarly, the
      barriers to collecting accurate accounts in qualitative studies of disrespect
      require astute interviewing and observation techniques. The participatory
      community-based and the critical sociology and human rights frameworks appear to
      provide a good basis for both researcher and participants to identify problems
      and determine possible solutions to the multiple factors that contribute to
      disrespect and abuse. The work-life conditions of midwives in the Global South
      are plagued with poor infrastructure and significantly low resources which deters
      respectful care while decreasing retention of workers. Researchers and policy
      makers have addressed disrespectful care by building human resource capacity, by
      strengthening professional organizations and by educating midwives in low
      resource countries. Furthermore, researchers encourage midwives not only to
      acquire attitudinal change and to adopt respectful maternity care skills, but
      also to emerge as leaders and change agents.Safe methods for conducting care
      while addressing low resources, skilled management of conflict and creative
      innovations to engage the community are all interventions that are being
      considered for quality improvement research. Tanzania is poised to evaluate the
      outcomes of education workshops that address all seven domains of respectful
      care.

PMID- 30285783
TI  - The relationship between physical literacy scores and adherence to Canadian
      physical activity and sedentary behaviour guidelines.
AB  - BACKGROUND: Physical literacy is an emerging construct in children's health
      promotion, and may impact their lifelong physical activity habits. However,
      recent data reveal that only a small portion of Canadian children are regularly
      physically active and/or meet sedentary behaviour guidelines. To our knowledge,
      no study has investigated the association between physical literacy and movement
      behaviour guidelines. Therefore, the purpose of this study was to examine the
      relationship between physical literacy scores in Canadian children who meet or do
      not meet physical activity and sedentary behaviour guidelines. METHODS: Children
      (n = 2956; 56.6% girls) aged 8-12 years from 10 Canadian cities had their
      physical literacy levels measured using the Canadian Assessment of Physical
      Literacy, which consists of four domains (Physical Competence; Daily Behaviour;
      Knowledge and Understanding; and Motivation and Confidence) that are aggregated
      to provide a composite physical literacy score. Physical activity levels were
      measured by pedometers, and sedentary behaviour was assessed through self-report
      questionnaire. Analyses were conducted separately for each guideline, comparing
      participants meeting versus those not meeting the guidelines. Comparisons were
      performed using MANOVA and logistic regression to control for age, gender, and
      seasonality. RESULTS: Participants meeting physical activity guidelines or
      sedentary behaviour guidelines had higher physical literacy domain scores for
      Physical Competence and for Motivation and Confidence compared to those not
      meeting either guideline (both p < 0.0001). Participants had increased odds of
      meeting physical activity guidelines and sedentary behaviour guidelines if they
      met the minimum recommended level of the Physical Competence and Motivation and
      Confidence domains. Significant age (OR 0.9; 95% CI: 0.8, 0.9), gender (OR 0.4;
      95% CI: 0.3, 0.5) and seasonality effects (OR 1.6; 95% CI: 1.2, 2.2 spring and OR
      1.7; 95% CI: 1.2, 2.5 summer, reference winter) were seen for physical activity
      guidelines, and age (OR 0.8; 95% CI: 0.7, 0.8) and gender effects (OR 1.7; 95%
      CI: 1.4, 2.0) for sedentary behaviour guidelines. Knowledge and Understanding of
      physical activity principles was not related to guideline adherence in either
      model. CONCLUSIONS: These cross-sectional findings demonstrate important
      associations between physical literacy and guideline adherence for physical
      activity and sedentary behaviour. Future research should explore the causality of
      these associations.

PMID- 30285784
TI  - Influence of the relative age effect on children's scores obtained from the
      Canadian assessment of physical literacy.
AB  - BACKGROUND: Age grouping by the imposition of a cut-off date, common in sports
      and education, promotes a relative age difference that is associated with
      developmental advantages for children who are born on the "early side" of the cut
      off date and disadvantages to those born later in the same year, which is known
      as the relative age effect (RAE) bias. Acquiring an adequate level of physical
      literacy is important for children to remain active for life. The Canadian
      Assessment of Physical Literacy (CAPL) is an assessment protocol that encompasses
      measures in the domains of children's Daily Behaviours, Physical Competence,
      Motivation and Confidence, and Knowledge and Understanding. The purpose of this
      study was to ascertain whether the CAPL scores were susceptible to the RAE, which
      could affect our interpretation of the CAPL findings. METHODS: This cross
      sectional study examined if scores obtained in the CAPL (i.e., the four domains
      individually and the total CAPL score) were susceptible to the RAE in children
      aged 8 to 12 years and, if so, which physical competence assessments (movement
      skills, cardiorespiratory, strength, muscular endurance, flexibility, and body
      composition measurements) were more susceptible. Participants (n = 8233, 49.8%
      boys) from the Royal Bank of Canada-CAPL Learn to Play project from 11 sites in
      seven Canadian provinces were tested using the CAPL protocol. RESULTS: Among boys
      and girls, the RAE was significantly associated with two and three of the four
      domain scores, respectively, after controlling for covariates. However, effect
      sizes were negligible for the comparisons between quarters of the year and
      physical literacy domains and overall scores. For the main effect of the relative
      age, boys and girls born in the first three months of the year were taller (F(3,
      4074) = 57.0, p < 0.001, f2 = 0.04 and F(3, 4107) = 58.4, p < 0.001, f2 = 0.04,
      respectively) and demonstrated greater muscular strength (F(3, 4037) = 29.2, p <
      0.001, f2 = 0.02 and F(3, 4077) = 25.1, p < 0.001, f2 = 0.02, respectively)
      compared with those born later in the same year. CONCLUSIONS: Collectively, our
      results suggest that the RAE bias is mainly negligible with regard to the domain
      scores and overall CAPL scores in this large sample of children.

PMID- 30285786
TI  - Early-BYRD: alternative early pacing and defibrillation lead replacement avoiding
      venous puncture.
AB  - BACKGROUND: In cases of lead failure after implantation of pacemakers (PM) or
      implantable cardioverter defibrillators (ICD) early lead replacement may be
      challenging. Puncture of the subclavian vein bears possible complications such as
      pneumothorax, hematothorax, and damage of leads to be left in place. To avoid
      venous puncture PM or ICD leads were replaced using a flexible polypropylene
      sheath (Byrd-sheath). METHOD: From January 2010 through December 2017, 55
      patients underwent early lead exchange avoiding venous puncture. Early lead
      exchange for this study was defined as a reintervention within 14 days after the
      initial lead implantation. The connector of the malfunctioning lead was cut off,
      and stabilized by a stiff stylet. After having cut off the plastic knob of the
      stylet, the lead was passed through the polypropylene sheath and the latter
      advanced into the subclavian vein with gentle rotational movements to gain access
      to the subclavian vein. After lead removal the polypropylene sheath was replaced
      by a peel away sheath a new lead inserted. RESULTS: Overall, 23 defibrillation
      leads and 34 pacing leads (16 right atrial leads, 17 right ventricular leads, and
      1 left ventricular lead) were successfully explanted. Access to the subclavian
      vein was uneventful, and blood loss minimal. Radiation exposure and fluoroscopy
      time were also negligible. CONCLUSION: The Byrd-sheath technique proved to be
      safe and successful in providing vein access within 2 weeks after initial lead
      implantation using the previously implanted lead and thus avoiding puncture of
      the subclavian vein.

PMID- 30285787
TI  - Non-orthogonal one-step calibration method for robotized transcranial magnetic
      stimulation.
AB  - BACKGROUND: Robotized transcranial magnetic stimulation (TMS) combines the
      benefits of neuro-navigation with automation and provides a precision brain
      stimulation method. Since the coil will normally remain unmounted between
      different clinical uses, hand/eye calibration and coil calibration are required
      before each experiment. Today, these two steps are still separate: hand/eye
      calibration is performed using methods proposed by Tsai/Lenz or Floris Ernst, and
      then the coil calibration is carried out based on the traditional TMS
      experimental step. The process is complex and time-consuming, and traditional
      coil calibration using a handheld probe is susceptible to greater calibration
      error. METHODS: A novel one-step calibration method has been developed to confirm
      hand/eye and coil calibration results by formulating a matrix equation system and
      estimating its solution. Hand/eye calibration and coil calibration are performed
      to confirm the pose relationships of the marker/end effector 'X', probe/end
      effector 'Y', and robot/world 'Z'. First, the coil is fixed on the end effector
      of the robot. During the one-step calibration process, a marker is mounted on the
      top of the coil and a calibration probe is fixed at the actual effective position
      of the coil. Next, the robot end effector is moved to a series of random
      positions 'A', the tracking data of marker 'B' and probe 'C' is obtained
      correspondingly. Then, a matrix equation system AX = ZB and AY = ZC can be
      acquired, and it is computed using a least-squares approach. Finally, the
      calibration probe is removed after calibration, while the marker remains fixed to
      the coil during the TMS experiment. The methods were evaluated based on
      simulation data and on experimental data from an optical tracking device. We
      compared our methods with two classical methods: the QR24 method proposed by
      Floris Ernst and the handheld coil calibration method. RESULTS: The new methods
      outperform the QR24 method in the aspect of translational accuracy and performs
      similarly in the aspect of rotational accuracy, the total translational error
      decreased more than fifty percent. The new approach also outperforms traditional
      handheld coil calibration of navigated TMS systems, the total translational error
      decreased three- to fourfold, and the rotational error decreased six- to
      eightfold. Furthermore, the convergence speed is improved 16- to 27-fold for the
      new algorithms. CONCLUSION: These results suggest that the new method can be used
      for hand/eye and coil calibration of a robotized TMS system. Two complex steps
      can be simplified using a least-squares approach.

PMID- 30285785
TI  - Peripheral immune system in aging and Alzheimer's disease.
AB  - Alzheimer's disease (AD) represents an urgent public health mandate. AD is no
      longer considered a neural-centric disease; rather, a plethora of recent studies
      strongly implicate a critical role played by neuroinflammation in the
      pathogeneses of AD and other neurodegenerative conditions. A close functional
      connection between the immune system and central nervous system is increasingly
      recognized. In late-onset AD, aging represents the most significant risk factor.
      Here, from an immunological perspective, we summarize the prominent molecular and
      cellular changes in the periphery of aging individuals and AD patients. Moreover,
      we review the knowledge gained in the past several years that implicate specific
      arms of the peripheral immune system and other types of immune responses in
      modulating AD progression. Taken together, these findings collectively emphasize
      a dynamic role of a concert of brain-extrinsic, peripheral signals in the aging
      and degenerative processes in the CNS. We believe that a systematic view
      synthesizing the vast amounts of existing results will help guide the development
      of next-generation therapeutics and inform future directions of AD investigation.

PMID- 30285788
TI  - Bladder preservation approach versus radical cystectomy for high-grade non-muscle
      invasive bladder cancer: a meta-analysis of cohort studies.
AB  - BACKGROUND: High-grade non-muscle-invasive bladder cancer is superficial;
      nonetheless, it is an aggressive cancer. Proper management strategy selection
      following transurethral resection between bladder preservation (BP) and radical
      cystectomy (RC) could result in delayed or excessive treatment. Hence, selecting
      the optimal treatment modality remains controversial to date. METHODS: We
      searched MEDLINE, The Cochrane Library, EMBASE, China National Knowledge
      Infrastructure, and Wanfang database through 12 April 2018. Quality and
      publication bias were assessed using the Newcastle-Ottawa Scale and
      Begg's/Egger's test. We collected 2-year, 5-year, 10-year, and 15-year survival
      rate and hazard ratio (HR) for overall survival (OS), cancer-specific survival
      (CSS), and progression-free survival (PFS). Using the Review Manager 5.2
      software, we used the odds ratio (OR) of specific years and HR for meta-analysis.
      Subgroup analysis was performed by the original tumor state, radical cystectomy
      timing, bladder preservation modality, and age. RESULTS: In total, 11 cohorts
      with 1735 patients were selected for the meta-analysis. All OR of OS supported BP
      as a better treatment option; however, all OR of PFS had no significant
      differences. As for CSS, only the 15-year OR reflected a statistical significance
      preferring RC. Subgroup analysis showed that BP is more appropriate for patients
      older than 65 and G3 tumor. Limited data demonstrated that late RC (> 3 months)
      is more effective compared to early RC (< 3 months) and intravesical Bacillus
      Calmette-Guerin was not statistically different from that of RC. The mixed BP
      modalities were significantly better compared to RC in OS and worse in CSS, with
      both having a very low evidence strength. CONCLUSIONS: BP is a superior treatment
      modality compare to RC, especially for older patients and T1G3 or lower grade
      tumors. However, the superior BP modality was unclear. Conversely, RC could be a
      better option for younger patients. More specifically, late RC may be more
      beneficial but had a very-low-level of evidence. Quality of life should be
      considered equal to survival outcome; hence, post-treatment follow-up needs to be
      performed. Prospective randomized studies should be performed to overcome the
      limitations of this meta-analysis study. REGISTRATION: Registration ID is
      CRD42018093491 .

PMID- 30285790
TI  - Lipid compositional changes and oxidation status of ultra-high temperature
      treated Milk.
AB  - BACKGROUND: Milk fat is one of the complex fat and most sensitive biochemical
      compounds towards auto-oxidation. To enhance the shelf life, milk is subjected to
      Ultra-high Temperature (UHT) treatment followed by aseptic packaging. During the
      storage, several chemical and biochemical changes take place in lipid fraction of
      UHT milk. In current investigation, the effect of UHT treatment and storage was
      determined by making a comparison in fatty acid profile, triglyceride
      composition, organic acids and lipid oxidation of the thermally treated and
      stored milk with raw milk, which was not reported in earlier investigations.
      METHODS: Raw milk samples were collected from the bulk storage facility of a
      dairy industry. The same milk was routed to UHT treatment and aseptically
      packaged samples were collected. The fatty acid profile, triglyceride
      composition, organic acids and lipid oxidation was determined in raw and UHT
      treated milk at 0, 30, 60 and 90 days. Fatty acid and triglyceride profile was
      determined on GC-MS while organic acids were determined by HPLC. For the
      measurement of induction period, professional Rancimat was used. Lipid oxidation
      was characterized through free fatty acids, peroxide value, anisidine value and
      conjugated dienes. RESULTS: Compositional attributes of milk remain unchanged
      during the entire length of storage. Concentrations of short-chain fatty acids in
      raw and UHT milk were 10.49% and 9.62%. UHT treatment resulted in 8.3% loss of
      short-chain fatty acids. Up to 30 days, storage did not have any significant
      effect on fatty acid profile of UHT milk. Concentration of medium-chain fatty
      acids in raw and UHT treated milk was 54.98% and 51.87%. After 30, 60 and 90 days
      of storage, concentration of medium chain fatty acids was found 51.23%, 47.23%
      and 42.82%, respectively. Concentration of C18:1 and C18:2 in raw and UHT milk
      was 26.86% and 25.43%, respectively. The loss of C18:1 and C18:2 in UHT treatment
      was 5.32%. After 30, 60 and 90 days of storage, the concentrations of C18:1 and
      C18:2 were 24.6%, 21.06% and 18.66%, respectively. Storage period of 30 days was
      found non-significant, while noticeable variations were found in triglyceride
      profile of 60 and 90 days old samples of UHT milk. UHT treatment and storage
      period significantly affected the concentration of organic acids in milk. After
      UHT treatment, concentration of lactic acid, acetic acid, citric acid, pyruvic
      acid, formic acid, succinic acid and oxalic acid increased by 3.45, 0.66, 3.57,
      0.68, 2.24, 2.16 and 1.63 mg/100 g. Effect of storage period on the production of
      organic acids in UHT milk was non-significant up to 30 days. After 60 days of
      storage period, the increase in concentration of lactic acid, acetic acid, citric
      acid, pyruvic acid, formic acid, succinic acid and oxalic acid was 3.79, 0.75,
      4.69, 0.78, 2.83, 3.03 and 2.38 mg/100 g. After 90 days of storage period, the
      increase in concentration of lactic acid, acetic acid, citric acid, pyruvic acid,
      formic acid, succinic acid and oxalic acid was 7.3, 2.18, 9.96, 3.58, 11.37, 5.22
      and 5.96%. Free fatty acids content of raw, UHT treated and 90 days old milk were
      0.08%, 0.11% and 0.19%. UHT treated version of milk showed similar peroxide
      value. While, the storage remarkably affected the peroxide value. After 30, 60
      and 90 days, peroxide value was 0.42, 0.62 and 1.18 (MeqO2/kg). Induction period
      of raw, UHT and stored milk was strongly correlated with peroxide value and fatty
      acid profile. Mean value of lipase activity in raw milk was 0.73 +/- 0.06
      MUmoles/ml. UHT treatment significantly decreased the lipase activity. The lipase
      activity of milk immediately after the UHT treatment was 0.18 +/- 0.02
      MUmoles/ml. Lipase activity of UHT milk after 30, 60 and 90 days of room
      temperature storage was 0.44 +/- 0.03, 0.95 +/- 0.07 and 1.14 +/- 0.09
      MUmoles/ml. Color, flavor and smell score decreased through the storage of UHT
      milk for 90 days. CONCLUSION: The results of this investigation revealed that
      fatty acid and triglyceride profile changed after 60 and 90 days of storage.
      Production of organic acids led to the drop of pH and sensory characteristics in
      UHT milk during the long-term storage. Induction period can be successfully used
      for the determination of anticipatory shelf life of UHT milk.

PMID- 30285789
TI  - Eating behavior and body composition across childhood: a prospective cohort
      study.
AB  - BACKGROUND: Although many cross-sectional studies reported that children with
      overweight or obesity show more food approaching and less food avoidant eating
      behaviors, there is a lack of replication in longitudinal studies. Therefore, the
      question remains whether healthcare professionals should target eating behaviors
      in childhood obesity interventions and prevention. We aimed to examine the
      longitudinal and possible bi-directional associations between eating behavior and
      body composition across childhood. METHODS: Data was included from 3331 children
      participating in the Generation R Study. At 4 and 10 years, mothers reported on
      the Child Eating Behavior Questionnaire including the subscales Food
      Responsiveness, Enjoyment of Food, Emotional Overeating and Satiety
      Responsiveness, and children's BMI was measured. Body composition, consisting of
      Fat Mass Index and Fat Free Mass Index was measured at 6 and 10 years with Dual
      energy-X-ray-Absorptiometry scans. RESULTS: Cross-lagged models including both
      directions of the BMI - eating behavior association showed that a higher BMI at
      the age of 4 years predicted more food responsiveness and enjoyment of food and
      less satiety responsiveness at 10 years (e.g. satiety responsiveness:beta = -
      0.10, 95% CI = - 0.14, - 0.07), but no associations were found in the opposite
      direction. For emotional overeating, however, a bi-directional association was
      found with BMI predicting more emotional eating and vice versa. Multivariable
      linear regression analyses showed that associations were stronger for Fat Mass
      Index than for Fat Free Mass Index. CONCLUSIONS: Results showed that a higher
      BMI, and particularly higher fat mass, at pre-school age predicted more food
      approaching and less food avoidant eating behaviors at the age of 10 years,
      rather than the hypothesized reverse direction. This suggests that increased
      adiposity in early childhood might upregulate appetite and related eating
      behaviors.

PMID- 30285792
TI  - Efficacy of regional arterial embolization before pleuropulmonary resection in 32
      patients with tuberculosis-destroyed lung.
AB  - BACKGROUND: Treatment of tuberculous-destroyed lung (TDL) with pleuropulmonary
      resection is challenging. Pulmonary hemorrhage is a frequent complication of this
      surgical procedure. Continuous efforts have been made to investigate clinical
      procedures that may reduce intraoperative bleeding effectively. In this study, we
      evaluated the feasibility and safety of regional arterial embolization before
      pleuropulmonary resection in patients with TDL. METHODS: The clinical data of 32
      patients with TDL were retrospectively reviewed and analyzed. These patients were
      admitted to the hospital between July 2009 and November 2016. All of the patients
      had moderate to massive hemoptysis and received regional arterial embolization in
      affected areas. Then, these patients underwent pleuropulmonary resection within 1
      week to 2 months after embolization. RESULTS: The results showed that 25 patients
      (78.1%) had bronchial artery, and all patients had non-bronchial systemic artery
      found in affected areas. Mild to moderate chest pain was reported in 6 patients,
      and fever was reported in 2 patients. Intraoperative blood loss during
      pleuropulmonary resection in patients who had received preoperative regional
      arterial embolization was 625.6 +/- 352.6 ml. Duration of the operation was 120.3
      +/- 75.2 min. Bronchopleural fistulae and empyema were found in 3 cases (9.4%).
      CONCLUSION: Performance of regional arterial embolization before pleuropulmonary
      resection offers a safe and feasible option that reduces intraoperative blood
      loss and shortens operative time in patients with TDL.

PMID- 30285791
TI  - Molecular signature of response to preoperative radiotherapy in locally advanced
      breast cancer.
AB  - BACKGROUND: Radiation therapy is an indispensable part of various treatment
      modalities for breast cancer. Specifically, for non-inflammatory locally advanced
      breast cancer (LABC) patients, preoperative radiotherapy (pRT) is currently
      indicated as a second line therapy in the event of lack of response to
      neoadjuvant chemotherapy. Still approximately one third of patients fails to
      respond favourably to pRT. The aim of this study was to explore molecular
      mechanisms underlying differential response to radiotherapy (RT) to identify
      predictive biomarkers and potential targets for increasing radiosensitivity.
      METHODS: The study was based on a cohort of 134 LABC patients, treated at the
      Institute of Oncology and Radiology of Serbia (IORS) with pRT, without previous
      or concomitant systemic therapy. Baseline transcriptional profiles were
      established using Agilent 60 K microarray platform in a subset of 23 formalin
      fixed paraffin-embedded (FFPE) LABC tumour samples of which 11 radiotherapy naive
      and 3 post-radiotherapy samples passed quality control and were used for
      downstream analysis. Biological networks and signalling pathways underlying
      differential response to RT were identified using Ingenuity Pathways Analysis
      software. Predictive value of candidate genes in the preoperative setting was
      further validated by qRT-PCR in an independent subset of 60 LABC samples of which
      42 had sufficient quality for data analysis, and in postoperative setting using
      microarray data from 344 node-negative breast cancer patients (Erasmus cohort,
      GSE2034 and GSE5327) treated either with surgery only (20%) or surgery with RT
      (80%). RESULTS: We identified 192 significantly differentially expressed genes
      (FDR < 0.10) between pRT-responsive and non-responsive tumours, related to
      regulation of cellular development, growth and proliferation, cell cycle control
      of chromosomal replication, glucose metabolism and NAD biosynthesis II route.
      APOA1, MAP3K4, and MMP14 genes were differentially expressed (FDR < 0.20) between
      pRT responders and non-responders in preoperative setting, while MAP3K4 was
      further validated as RT-specific predictive biomarker of distant metastasis free
      survival (HR = 2.54, [95%CI:1.42-4.55], p = 0.002) in the postoperative setting.
      CONCLUSIONS: This study pinpoints MAP3K4 as a putative biomarker of response to
      RT in both preoperative and postoperative settings and a potential target for
      radiosensitising combination therapy, warranting further pre-clinical studies and
      prospective clinical validation.

PMID- 30285793
TI  - Melanoma cell-secreted exosomal miR-155-5p induce proangiogenic switch of cancer
      associated fibroblasts via SOCS1/JAK2/STAT3 signaling pathway.
AB  - BACKGROUND: Cancer-associated fibroblasts (CAFs) have been widely reported to
      promote tumor angiogenesis. However, the underlying mechanisms of the
      proangiogenic switch of CAFs remain poorly understood. This study aims to clarify
      the mechanisms underlying the proangiogenic switch of CAFs. METHODS: NIH/3T3
      cells were treated with B16 and B16F10-derived exosomes. Then the CAFs markers
      and proangiogenic factors were detected by RT-PCR and Western blot. CCK-8 assay,
      transwell migration assay, tube formation assay, and in vivo Matrigel plug assay
      were conducted to determine the proangiogenic capability of CAFs. Western blot
      and AG490 were used to investigate the role of Janus kinase 2/signal transducer
      and activator of transcription 3 (JAK2/STAT3) signaling pathway in the
      proangiogenic switch of CAFs. Bioinformatics analysis, luciferase reporter assay,
      microRNA mimic and inhibitor, and xenograft models were used to investigate the
      role of mmu-miR-155-5p (miR-155) in the proangiogenic switch of CAFs. RESULTS: In
      this study, we show that melanoma cell-secreted exosomes can induce reprogramming
      of fibroblasts into CAFs and that exosomal miR-155 can trigger the proangiogenic
      switch of CAFs. Mechanistically exosomal miR-155 can be delivered into
      fibroblasts and promote the expression of proangiogenic factors, including
      vascular endothelial growth factor A (VEGFa), fibroblast growth factor 2 (FGF2),
      and matrix metalloproteinase 9 (MMP9), by directly targeting suppressor of
      cytokine signaling 1 (SOCS1). Downregulation of SOCS1 activates JAK2/STAT3
      signaling pathway and elevates the expression levels of VEGFa, FGF2, and MMP9 in
      fibroblasts. Treatment with exosomes containing overexpressed miR-155 can promote
      angiogenesis, and the reduction of miR-155 in melanoma cell-secreted exosomes
      alleviates angiogenesis in vitro and in vivo. CONCLUSIONS: These results
      demonstrate that by promoting the expression of proangiogenic factors in
      recipient fibroblasts via SOCS1/JAK2/STAT3 signaling pathway, melanoma cell
      secreted exosomal miR-155 can induce the proangiogenic switch of CAFs. Although
      tumor angiogenesis is modulated by various factors, exosomal miR-155 may be a
      potential target for controlling melanoma angiogenesis and used to set up novel
      strategies to treat melanoma.

PMID- 30285794
TI  - Prosthesis-patient mismatch after mitral valve replacement: a single-centered
      retrospective analysis in East China.
AB  - BACKGROUND: Prosthesis-patient mismatch (PPM) may affect the clinical outcomes of
      patients undergoing mitral valve replacement (MVR) surgery. We aimed to
      investigate the incidence of PPM of the mitral position in our center and analyze
      the possible predictors of PPM as well as its effect on short-term outcomes.
      METHODS: We retrospectively examined all consecutive patients with isolated or
      concomitant MVR at our center from 2013 to 2015. PPM was defined as an indexed
      effective orifice area (iEOA) of <=1.2 cm2/m2. After inclusion and exclusion, a
      total of 1067 patients were analyzed. The baseline information were collected and
      compared between the two groups. Multivariate logistic regression analysis was
      conducted to determine the preoperative predictors of PPM as well as the effect
      of PPM on early mortality. RESULTS: A total of 1067 patients were included in the
      study. PPM was detected in 15.9% of the patients while 12 patients (1.12%) met
      the criteria for severe PPM. Patients with PPM compared to the non-PPM patients
      had higher age, larger body surface area and were more likely to be male and
      obese. Logistic regression analysis showed that higher age, larger BSA,
      bioprosthesis and smaller left ventricle end-diastolic diameter were predictors
      of PPM. There were no significant differences between the PPM and non-PPM groups
      regarding post-operative complications. Logistic regression analysis showed that
      PPM was not a risk factor of short-term mortality (P = 0.654). Also, there were
      no significant differences regarding short-/mid-term heart function between the
      PPM and non PPM groups (P = 0.902). CONCLUSIONS: Our results demonstrated that
      higher age, bioprosthesis, larger BSA and smaller left ventricle size were
      associated with mitral PPM. However, PPM was not associated with poorer early
      outcomes after MVR surgery. In eastern of China, the prevalence of mitral valve
      stenosis is high; therefore, whether the standard PPM criteria are suitable for
      patients of this district needs to be further verified.

PMID- 30285795
TI  - Percutaneous versus thoracoscopic ablation of symptomatic paroxysmal atrial
      fibrillation: a randomised controlled trial - the FAST II study.
AB  - BACKGROUND: The most efficient first-time invasive treatment, for achieving sinus
      rhythm, in symptomatic paroxysmal atrial fibrillation has not been established.
      We aimed to compare percutaneous catheter and video-assisted thoracoscopic
      pulmonary vein radiofrequency ablation in patients referred for first-time
      invasive treatment due to symptomatic paroxysmal atrial fibrillation. The primary
      outcome of interest was the prevalence of atrial fibrillation with and without
      anti-arrhythmic drugs at 12 months. METHODS: Ninety patients were planned to be
      randomised to either video-assisted thoracoscopic radiofrequency pulmonary vein
      ablation with concomitant left atrial appendage excision or percutaneous catheter
      pulmonary vein ablation. Episodes of atrial fibrillation were defined as more
      than 30 s of atrial fibrillation observed on Holter monitoring/telemetry or
      clinical episodes documented by ECG. RESULTS: The study was terminated
      prematurely due to a lack of eligible patients. Only 21 patients were randomised
      and treated according to the study protocol. Thoracoscopic pulmonary vein
      ablation was performed in 10 patients, and 11 patients were treated with catheter
      ablation. The absence of atrial fibrillation without the use of anti-arrhythmic
      drugs throughout the follow-up was observed in 70% of patients following
      thoracoscopic pulmonary vein ablation and 18% after catheter ablation (p < 0.03).
      CONCLUSION: Thoracoscopic pulmonary vein ablation may be superior to catheter
      ablation for first-time invasive treatment of symptomatic paroxysmal atrial
      fibrillation with regard to obtaining sinus rhythm off anti-arrhythmic drugs 12
      months postoperative. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT01336075 . Registered April 15th, 2011.

PMID- 30285796
TI  - Revising the motivation and confidence domain of the Canadian assessment of
      physical literacy.
AB  - BACKGROUND: The Motivation and Confidence domain questionnaire in the Canadian
      Assessment of Physical Literacy (CAPL) was lengthy (36 single items that
      aggregate to five subscales), and thus burdensome to both participants and
      practitioners. The purpose of this study was to use factor analysis to refine the
      Motivation and Confidence domain to be used in the CAPL-Second Edition (CAPL-2).
      METHODS: Children, primarily recruited through free-of-charge summer day camps (n
      = 205, Mage = 9.50 years, SD = 1.14, 50.7% girls), completed the CAPL-2 protocol,
      and two survey versions of the Motivation and Confidence questionnaire. Survey 1
      contained the Motivation and Confidence questionnaire items from the original
      CAPL, whereas Survey 2 contained a battery of items informed by self
      determination theory to assess motivation and confidence. First, factor analyses
      were performed on individual questionnaires to examine validity evidence (i.e.,
      internal structure) and score reliability (i.e., coefficient H and omega total).
      Second, factor analyses were performed on different combinations of
      questionnaires to establish the least burdensome yet well-fitted and
      theoretically aligned model. RESULTS: The assessment of adequacy and
      predilection, based on 16 single items as originally conceptualized within the
      CAPL, was not a good fit to the data. Therefore, a revised and shorter version of
      these scales was proposed, based on exploratory factor analysis. The self
      determination theory items provided a good fit to the data; however, identified,
      introjected, and external regulation had low score reliability. Overall, a model
      comprising three single items for each of the following subscales was proposed
      for use within the CAPL-2: adequacy, predilection, intrinsic motivation, and
      perceived competence satisfaction. This revised domain fit well within the
      overall CAPL-2 model specifying a higher-order physical literacy factor
      (MLRchi2(63) = 81.45, p = 0.06, CFI = 0.908, RMSEA = 0.038, 90% CI (0.00,
      0.060)). CONCLUSIONS: The revised and much shorter questionnaire of 12 items that
      aggregate to four subscales within the domain of Motivation and Confidence is
      recommended for use in the CAPL-2. The revised domain is aligned with the
      definition of motivation and confidence within physical literacy and has clearer
      instructions for completion.

PMID- 30285797
TI  - An exploratory analysis of missing data from the Royal Bank of Canada (RBC) Learn
      to Play - Canadian Assessment of Physical Literacy (CAPL) project.
AB  - BACKGROUND: Physical literacy comprises a range of tests over four domains
      (Physical Competence, Daily Behaviour, Motivation and Confidence, and Knowledge
      and Understanding). The patterns of missing data in large field test batteries
      such as those for physical literacy are largely unknown. Therefore, the aim of
      this paper was to explore the patterns and possible reasons for missing data in
      the Royal Bank of Canada Learn to Play-Canadian Assessment of Physical Literacy
      (RBC Learn to Play-CAPL) project. METHODS: A total of 10,034 Canadian children
      aged 8 to 12 years participated in the RBC Learn to Play-CAPL project. A 32
      variable subset from the larger CAPL dataset was used for these analyses. Several
      R packages ("Hmisc", "mice", "VIM") were used to generate matrices and plots of
      missing data, and to perform multiple imputations. RESULTS: Overall, the
      proportion of missing data for individual measures and domains ranged from 0.0 to
      33.8%, with the average proportion of missing data being 4.0%. The largest
      proportion of missing data in CAPL was the pedometer step counts, followed by the
      components of the Physical Competence domain and the Children's Self-Perception
      of Adequacy in and Predilection for Physical Activity subscales. When domain
      scores were regressed on five imputed subsets with the original subset as the
      reference, there were small and statistically detectable differences in the Daily
      Behaviour score (beta = - 1.6 to - 1.7, p < 0.001). However, for the other domain
      scores the differences were negligible and statistically undetectable (beta = -
      0.01 to - 0.06, p > 0.05). CONCLUSIONS: This study has implications for other
      researchers or educators who are creating or using large field-based assessment
      measures in the areas of physical literacy, physical activity, or physical
      fitness, as this study demonstrates where problems in data collection can arise
      and how missing data can be avoided. When large proportions of missing data are
      present, imputation techniques, correction factors, or other treatment options
      may be required.

PMID- 30285799
TI  - Identifying individuals with chronic pain after knee replacement: a population
      cohort, cluster-analysis of Oxford knee scores in 128,145 patients from the
      English National Health Service.
AB  - BACKGROUND: Approximately one in five patients undergoing knee replacement
      surgery experience chronic pain after their operation, which can negatively
      impact on their quality of life. In order to develop and evaluate interventions
      to improve the management of chronic post-surgical pain, we aimed to derive a cut
      off point in the Oxford Knee Score pain subscale to identify patients with
      chronic pain following knee replacement, and to characterise these patients using
      self-reported outcomes. METHODS: Data from the English Patient-Reported Outcome
      Measures (PROMs) programme were used. This comprised patient-reported data from
      128,145 patients who underwent primary knee replacement surgery in England
      between 2012 and 2015. Cluster analysis was applied to derive a cut-off point on
      the pain subscale of the Oxford Knee Score. RESULTS: A high-pain group was
      identified, described by a maximum of 14 points in the Oxford Knee Score pain
      subscale six months after surgery. The high-pain group, comprising 15% of the
      sample, was characterised by severe and frequent problems in all pain dimensions,
      particularly in pain severity, night pain and limping, as well as in all
      dimensions of health-related quality of life. CONCLUSIONS: Patients with Oxford
      Knee Score pain subscale scores of 14 or less at six months after knee
      replacement can be considered to be in chronic pain that is likely to negatively
      affect their quality of life. This derived cut-off can be used for patient
      selection in research settings to design and assess interventions that support
      patients in their management of chronic post-surgical pain.

PMID- 30285798
TI  - An ABCG2 non-substrate anticancer agent FL118 targets drug-resistant cancer stem
      like cells and overcomes treatment resistance of human pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is a deadly disease with a very low 5-year patient
      survival rate of 6-8%. The major challenges of eliminating pancreatic cancer are
      treatment resistance and stromal barriers to optimal drug access within the
      tumor. Therefore, effective molecular targeting drugs with high intra-tumor
      access and retention are urgently needed for managing this devastating disease in
      the clinic. METHODS: This study has used the following in vitro and in vivo
      techniques for the investigation of exceptional anticancer drug FL118's efficacy
      in treatment of resistant pancreatic cancer: cell culture; immunoblotting
      analysis to test protein expression; DNA sub-G1 flow cytometry analyses to test
      cell death; MTT assay to test cell viability; pancreatic cancer stem cell assays
      (fluorescence microscopy tracing; matrigel assay; CD44-positive cell colony
      formation assay); human luciferase-labeled pancreatic tumor orthotopic animal
      model in vivo imaging; pancreatic cancer patient-derived xenograft (PDX) animal
      models; and toxicology studies with immune-competent BALB/cj mice and beagle
      dogs. RESULTS: Our studies found that FL118 alone preferentially killed cisplatin
      resistant cancer cells, while a combination of FL118 with cisplatin
      synergistically killed resistant pancreatic cancer cells and reduced spheroid
      formation of treatment-resistant pancreatic cancer stem-like cells. Furthermore,
      using in vivo-imaging, we found that FL118 in combination with cisplatin strongly
      inhibited both drug-resistant pancreatic xenograft tumor growth and metastasis.
      In PDX model, we demonstrated that FL118 alone effectively eliminated PDX tumors,
      while FL118 in combination with gemcitabine eliminated PDX tumors that showed
      relative resistance (less sensitivity) to treatment with FL118. These FL118
      efficacy results are consistent with our molecular-targeting data showing that
      FL118 inhibited the expression of multiple antiapoptotic proteins (survivin, Mcl
      1, XIAP, cIAP2) and ERCC6, a critical regulator of DNA repair, in treatment
      resistant pancreatic stem-like cancer cells. Furthermore, FL118 toxicity studies
      in BALB/cj mice and beagle dogs indicated that FL118 exhibits favorable
      hematopoietic and biochemical toxicities. CONCLUSION: Together, our studies
      suggest that FL118 is a promising anticancer drug for further clinical
      development to effectively treat drug-resistant pancreatic cancer alone or in
      combination with other pancreatic cancer chemotherapeutic drugs.

PMID- 30285800
TI  - Satisfactory virological response and fibrosis improvement of sofosbuvir-based
      regimens for Chinese patients with hepatitis C virus genotype 3 infection:
      results of a real-world cohort study.
AB  - BACKGROUND: Chronic hepatitis C virus (HCV) genotype (GT) 3 infection with
      advanced liver disease has emerged as a challenging to treat by direct-acting
      antivirals (DAAs), but the efficacy of DAAs in Chinese HCV-GT3 patients is rarely
      reported. This study aimed to analyze the efficacy of sofosbuvir (SOF)-based
      regimens in Chinese patients with HCV-GT3 and compensated liver disease. METHODS:
      This was a registered retrospective study. All patients had completed at least 12
      weeks SOF-based regimens therapy (with or without RBV), and were followed up for
      at least 24 weeks after therapy discontinuation. The primary endpoint was
      sustained virological response 24 weeks after end of therapy (SVR24). RESULTS: A
      total of 102 patients who completed at least 12 weeks therapy were finally
      included, with 57 in SOF + Daclatasvir (SOF + DCV), 24 in SOF + DCV + ribavirin
      (RBV) and 21 in SOF/Velpatasvir (SOF/VEL). The total SVR24 rate was achieved in
      90.20% (92/102), with 85.96% (49/57) in SOF + DCV, 91.67% (22/24) in SOF + DCV +
      RBV and 100.00% (21/21) in SOF/VEL. Among 10 relapsed patients (8 in SOF + DCV
      and 2 in SOF + DCV + RBV), the short course (12 weeks) of therapy and no RBV
      addition may be the leading cause. In this cohort, the SVR24 rate was not
      statistically different between patients with and without cirrhosis (81.82%
      [27/33] vs. 94.20% [65/69], P = 0.073). Additionally, both FIB-4 (4.03 vs. 2.08,
      P < 0.001) and APRI (2.15 vs. 0.68, P < 0.001) scores were significant improved
      from baseline to week 24 after completion of therapy, regardless of the presence
      of cirrhosis. CONCLUSION: SOF-based regimens are highly effective in viral
      clearance and fibrosis remission for Chinese patients with HCV-GT3 infection. If
      available, SOF/VEL should be first considered.

PMID- 30285801
TI  - Plasticity changes in forebrain activity and functional connectivity during
      neuropathic pain development in rats with sciatic spared nerve injury.
AB  - Neuropathic pain is a major worldwide health problem. Although central
      sensitization has been reported in well-established neuropathic conditions,
      information on the acute brain activation patterns in response to peripheral
      nerve injury is lacking. This study first mapped the brain activity in rats
      immediately following spared nerve injury (SNI) of the sciatic nerve. Using blood
      oxygenation-level-dependent functional magnetic resonance imaging (BOLD-fMRI), we
      observed sustained activation in the bilateral insular cortices (ICs), primary
      somatosensory cortex (S1), and cingulate cortex. Second, this study sought to
      link this sustained activation pattern with brain sensitization. Using manganese
      enhanced magnetic resonance imaging (MEMRI), we observed enhanced activity in the
      ipsilateral anterior IC (AIC) in free-moving SNI rats on Days 1 and 8 post-SNI.
      Furthermore, enhanced functional connectivity between the ipsilateral AIC,
      bilateral rostral AIC, and S1 was observed on Day 8 post-SNI. Chronic
      electrophysiological recording experiments were conducted to confirm the tonic
      neuronal activation in selected brain regions. Our data provide evidence of tonic
      activation-dependent brain sensitization during neuropathic pain development and
      offer evidence that the plasticity changes in the IC and S1 may contribute to
      neuropathic pain development.

PMID- 30285802
TI  - Dietary supplement use among undergraduate male students in health and non-health
      cluster colleges of a public-sector university in Dammam, Saudi Arabia.
AB  - BACKGROUND: Dietary supplements (DS) are nutraceuticals that improve overall
      health and well-being of an individual as well as reduce the risk of diseases.
      Evidence indicates a rising prevalence of these products worldwide especially
      among college students. Studies have reported an increasing use of supplements
      among Saudi students. However, the scope of those researches was limited to
      prevalence data. Hence, the aim of our study was to document the prevalence,
      opinions, attitudes, reasons for use and monthly cost attributed to dietary
      supplement use. METHODS: A 3-month cross-sectional study was conducted to
      evaluate use of dietary supplement among health and non-health college students
      at a public-sector university in Dammam city, Saudi Arabia. It was conducted
      using Arabic version of the Dietary supplement questionnaire (DSQ-A). A total of
      469 male students responded to the survey giving a response rate of 93.8%. The
      students were from ten colleges of the university. The data was analyzed by SPSS
      version 22. The study was approved by Institutional Review Board of Imam
      Abdulrahman Bin Faisal University, Dammam, Saudi Arabia (IRB-UGS-2018-05-074).
      RESULTS: The overall prevalence of dietary supplement use in the university was
      29.42%. In health cluster colleges, it was reported at 35.91% while in non-health
      cluster college it was 23.69%. Maintaining general health and well-being was the
      most common reason for use. Prevalence of multivitamins and whey proteins was
      approximately 23%. Average monthly cost of supplement was SAR 278.92 (USD 74.39).
      Cost was positively correlated (rho = 0.305) with satisfaction score. Students
      preferred brand products (16.4%). 41.4% students opined that DS may prevent
      chronic illness if used regularly and agreed that they are good for health.
      Majority of students (65%) recommended DS use only upon physician's
      recommendation. College clusters and study-year was associated (p-value< 0.01)
      with students' opinion. Students in health cluster colleges were more likely to
      recommend supplements (OR 3.715, p-value< 0.0001). CONCLUSION: Prevalence of
      dietary supplement use was lower than other local and international university
      students. Health cluster colleges had higher prevalence as compared to non-health
      cluster colleges. Multivitamins and whey protein were the most commonly used
      types of DS. Students preferred brand products, had positive opinions and
      attitudes towards dietary supplement. However, they recommended supplements use
      to others only upon a physician's recommendation.

PMID- 30285804
TI  - Pain neurophysiology knowledge among physical therapy students in Saudi Arabia: a
      cross-sectional study.
AB  - BACKGROUND: Pain is a leading cause of disability and accounts for many hospital
      and physical therapy visits. Current pain science understanding has evolved and
      changed substantially in the past 20 years; however, university health science
      curricula may not have progressed at the same rate. This study aimed to examine
      knowledge about pain neurophysiology among physical therapy students in Saudi
      Arabia, and to compare their knowledge across different education levels and by
      gender. METHODS: A cross-sectional study conducted to examine the pain
      neurophysiology knowledge among college physical therapy students in Saudi
      Arabia. The Revised Neurophysiology of Pain Questionnaire (12 items) was used.
      Descriptive statistics including frequencies and percentages were used to
      describe the sample. Analysis of variance and t-test were also used to examine
      the significant differences between scores. RESULTS: Physical therapy students (n
      = 202) from 18 different universities in Saudi Arabia participated in this study.
      The mean score of the participants on the questionnaire was 6.20 +/- 2.07 (i.e.,
      52% +/- 17%) and there was no significance difference between males and females.
      There was a statistically significant incremental increase in total score through
      the educational process (P < 0.05); however, this increase was very small
      comparing early- and final educational-level students (8% in RNPQ). CONCLUSION:
      While final year physical therapy students showed higher levels of pain science
      knowledge than those at the beginning of their course, the magnitude of the
      difference was small and likely of little meaningful relevance. This may reflect
      the need for more emphasis on pain science in the physical therapy curriculum in
      Saudi Arabia.

PMID- 30285803
TI  - Foxf2 plays a dual role during transforming growth factor beta-induced epithelial
      to mesenchymal transition by promoting apoptosis yet enabling cell junction
      dissolution and migration.
AB  - BACKGROUND: The most life-threatening step during malignant tumor progression is
      reached when cancer cells leave the primary tumor mass and seed metastasis in
      distant organs. To infiltrate the surrounding tissue and disseminate throughout
      the body, single motile tumor cells leave the tumor mass by breaking down cell
      cell contacts in a process called epithelial to mesenchymal transition (EMT). An
      EMT is a complex molecular and cellular program enabling epithelial cells to
      abandon their differentiated phenotype, including cell-cell adhesion and cell
      polarity, and to acquire mesenchymal features and invasive properties. METHODS:
      We employed gene expression profiling and functional experiments to study
      transcriptional control of transforming growth factor (TGF)beta-induced EMT in
      normal murine mammary gland epithelial (NMuMG) cells. RESULTS: We identified that
      expression of the transcription factor forkhead box protein F2 (Foxf2) is
      upregulated during the EMT process. Although it is not required to gain
      mesenchymal markers, Foxf2 is essential for the disruption of cell junctions and
      the downregulation of epithelial markers in NMuMG cells treated with TGFbeta.
      Foxf2 is critical for the downregulation of E-cadherin by promoting the
      expression of the transcriptional repressors of E-cadherin, Zeb1 and Zeb2, while
      repressing expression of the epithelial maintenance factor Id2 and miRNA 200
      family members. Moreover, Foxf2 is required for TGFbeta-mediated apoptosis during
      EMT by the transcriptional activation of the proapoptotic BH3-only protein Noxa
      and by the negative regulation of epidermal growth factor receptor (EGFR)
      mediated survival signaling through direct repression of its ligands betacellulin
      and amphiregulin. The dual function of Foxf2 during EMT is underscored by the
      finding that high Foxf2 expression correlates with good prognosis in patients
      with early noninvasive stages of breast cancer, but with poor prognosis in
      advanced breast cancer. CONCLUSIONS: Our data identify the transcription factor
      Foxf2 as one of the important regulators of EMT, displaying a dual function in
      promoting tumor cell apoptosis as well as tumor cell migration.

PMID- 30285805
TI  - BHLHE40 confers a pro-survival and pro-metastatic phenotype to breast cancer
      cells by modulating HBEGF secretion.
AB  - BACKGROUND: Metastasis is responsible for a significant number of breast cancer
      related deaths. Hypoxia, a primary driving force of cancer metastasis, induces
      the expression of BHLHE40, a transcription regulator. This study aimed to
      elucidate the function of BHLHE40 in the metastatic process of breast cancer
      cells. METHODS: To define the role of BHLHE40 in breast cancer, BHLHE40
      expression was knocked down by a lentiviral construct expressing a short hairpin
      RNA against BHLHE40 or knocked out by the CRISPR/Cas9 editing system. Orthotopic
      xenograft and experimental metastasis (tail vein injection) mouse models were
      used to analyze the role of BHLHE40 in lung metastasis of breast cancer. Global
      gene expression analysis and public database mining were performed to identify
      signaling pathways regulated by BHLHE40 in breast cancer. The action mechanism of
      BHLHE40 was examined by chromatin immunoprecipitation (ChIP), co
      immunoprecipitation (CoIP), exosome analysis, and cell-based assays for
      metastatic potential. RESULTS: BHLHE40 knockdown significantly reduced primary
      tumor growth and lung metastasis in orthotopic xenograft and experimental
      metastasis models of breast cancer. Gene expression analysis implicated a role of
      BHLHE40 in transcriptional activation of heparin-binding epidermal growth factor
      (HBEGF). ChIP and CoIP assays revealed that BHLHE40 induces HBEGF transcription
      by blocking DNA binding of histone deacetylases (HDAC)1 and HDAC2. Cell-based
      assays showed that HBEGF is secreted through exosomes and acts to promote cell
      survival and migration. Public databases provided evidence linking high
      expression of BHLHE40 and HBEGF to poor prognosis of triple-negative breast
      cancer. CONCLUSION: This study reveals a novel role of BHLHE40 in promoting tumor
      cell survival and migration by regulating HBEGF secretion.

PMID- 30285806
TI  - Image guidance and positioning accuracy in clinical practice: influence of
      positioning errors and imaging dose on the real dose distribution for head and
      neck cancer treatment.
AB  - BACKGROUND: Modern radiotherapy offers the possibility of highly accurate tumor
      treatment. To benefit from this precision at its best, regular positioning
      verification is necessary. By the use of image-guided radiotherapy and the
      application of safety margins the influence of positioning inaccuracies can be
      counteracted. In this study the effect of additional imaging dose by set-up
      verification is compared with the effect of dose smearing by positioning
      inaccuracies for a collective of head-and-neck cancer patients. METHODS: This
      study is based on treatment plans of 40 head-and-neck cancer patients. To
      evaluate the imaging dose several image guidance scenarios with different
      energies, techniques and frequencies were simulated and added to the original
      plan. The influence of the positioning inaccuracies was assessed by the use of
      real applied table shifts for positioning. The isocenters were shifted back
      appropriately to these values to simulate that no positioning correction had been
      performed. For the single fractions the shifted plans were summed considering
      three different scenarios: The summation of only shifted plans, the consideration
      of the original plan for the fractions with set-up verification, and the addition
      of the extra imaging dose to the latter. For both effects (additional imaging
      dose and dose smearing), plans were analyzed and compared considering target
      coverage, sparing of organs at risk (OAR) and normal tissue complication
      probability (NTCP). RESULTS: Daily verification of the patient positioning using
      3D imaging with MV energies result in non-negligible high doses. kV imaging has
      only marginal influence on plan quality, primarily related to sparing of organs
      at risk, even with daily 3D imaging. For this collective, sparing of organs at
      risk and NTCP are worse due to potential positioning errors. CONCLUSION: Regular
      set-up verification is essential for precise radiation treatment. Relating to the
      additional dose, the use of kV modalities is uncritical for any frequency and
      technique. Dose smearing due to positioning errors for this collective mainly
      resulted in a decrease of OAR sparing. Target coverage also suffered from the
      positioning inaccuracies, especially for individual patients. Taking into account
      both examined effects the relevance of an extensive IGRT is clearly present, even
      at the expense of additional imaging dose and time expenditure.

PMID- 30285807
TI  - Adjacent segment degeneration or disease after cervical total disc replacement: a
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Anterior cervical discectomy and fusion (ACDF) has been widely used
      in cervical spondylosis, but adjacent segment degeneration/disease (ASD) was
      inevitable. Cervical total disc replacement (TDR) could reduce the stress of
      adjacent segments and retard ASD in theory, but the superiority has not been
      determined yet. This analysis aimed that whether TDR was superior to ACDF for
      decreasing adjacent segment degeneration (ASDeg) and adjacent segment disease
      (ASDis). METHODS: A meta-analysis was performed according to the guidelines of
      the Cochrane Collaboration with PubMed, EMBASE, Cochrane Library and CBM (China
      Biological Medicine) databases. It included randomized controlled trials (RCTs)
      that reported ASDeg, ASDis, and reoperation on adjacent segments after TDR and
      ACDF. Two investigators independently selected trials, assessed methodological
      quality, and evaluated the quality of this meta-analysis using the grades of
      recommendation, assessment, development, and evaluation (GRADE) approach.
      RESULTS: Eleven studies with 2632 patients were included in the meta-analysis.
      The overall rate of ASD in TDR group was lower than ACDF group (OR = 0.6; 95% CI
      [0.38, 0.73]; P < 0.00001). Both the incidence of ASDeg and the reoperation rate
      were statistically lower in the TDR group than in the ACDF group (OR = 0.58, P <
      0.00001; OR = 0.52, P = 0.01, respectively). Subgroup analysis was performed
      according to the follow-up time and trial site; the rate of ASDeg was lower in
      patients underwent TDR no matter the follow-up time, and TDR tended to increase
      the superiority across time. The rate of ASDeg was also lower with TDR both in
      the USA and China (P < 0.0001, P = 0.03, respectively). But the cost
      effectiveness result might be prone to neither of the two surgery approaches.
      According to GRADE, the overall quality of this meta-analysis was moderate.
      CONCLUSIONS: TDR decreased the rates of ASDeg and reoperation compared with that
      of ACDF, and the superiority may become more apparent over time. We cautiously
      and slightly suggest adopting TDR according to the GRADE but may not believe it
      excessively.

PMID- 30285808
TI  - Enhanced efficacy of histone deacetylase inhibitor combined with bromodomain
      inhibitor in glioblastoma.
AB  - BACKGROUND: Glioblastoma (GBM) is the most common and most malignant primary
      brain cancer in adults. Despite multimodality treatment, the prognosis is still
      poor. Therefore, further work is urgently required to discover novel therapeutic
      strategies for GBM treatment. METHODS: The synergistic effects of cotreatment
      with the histone deacetylase (HDAC) inhibitor panobinostat and bromodomain
      inhibitor JQ1 or OTX015 were validated using cell viability assays in GBM cell
      lines. Furthermore, the inhibitory mechanisms were investigated via an EdU
      proliferation assay, an apoptosis assay, qPCR, Western blot and RNAseq analyses.
      RESULTS: We found that the cotreatment with panobinostat and JQ1 or OTX015
      synergistically inhibited cell viability in GBM cells. The cotreatment with
      panobinostat and JQ1 or OTX015 markedly inhibited cell proliferation and induced
      apoptosis in GBM cells. Compared with treatment with each drug alone, the
      cotreatment with panobinostat and JQ1 induced more profound caspase 3/7
      activation and cytotoxicity. Mechanistic investigation showed that combination of
      panobinostat with JQ1 or OTX015 results in stronger repression of GBM-associated
      oncogenic genes or pathways as well as higher induction of GBM-associated tumor
      suppressive genes. CONCLUSION: Our study demonstrated that HDAC inhibitor and
      bromodomain inhibitor had synergistical efficacy against GBM cells. The
      cotreatment with HDAC inhibitor and bromodomain inhibitor warrants further
      attention in GBM therapy.

PMID- 30285811
TI  - Cost-effectiveness analysis of single use negative pressure wound therapy
      dressings (sNPWT) compared to standard of care in reducing surgical site
      complications (SSC) in patients undergoing coronary artery bypass grafting
      surgery.
AB  - BACKGROUND: There is a growing interest in using negative pressure wound therapy
      in closed surgical incision to prevent wound complications which continue to
      persist following surgery despite advances in infection measures. OBJECTIVES: To
      estimate the cost-effectiveness of single use negative pressure wound therapy
      (sNPWT) compared to standard of care in patients following coronary artery bypass
      grafting surgery (CABG) procedure to reduce surgical site complications (SSC)
      defined as dehiscence and sternotomy infections. METHOD: A decision analytic
      model was developed from the Germany Statutory Health Insurance payer's
      perspective over a 12-week time horizon. Baseline data on SSC, revision
      operations, length of stay, and readmissions were obtained from a prospective
      observational study of 2621 CABG patients in Germany. Effectiveness data for
      sNPWT was taken from a randomised open label trial conducted in Poland which
      randomised 80 patients to treatment with either sNPWT or standard care. Cost data
      (in Euros) were taken from the relevant diagnostic related groups and published
      literature. RESULTS: The clinical study reported an increase in wounds that
      healed without complications 37/40 (92.5%) in the sNPWT compared to 30/40 (75%)
      patients in the SC group p = 0.03. The model estimated sNPWT resulted in 0.989
      complications avoided compared to 0.952 and the estimated quality adjusted life
      years were 0.8904 and 0.8593 per patient compared to standard care. The estimated
      mean cost per patient was ?19,986 for sNPWT compared to ?20,572 for SC resulting
      in cost-saving of ?586. The findings were robust to a range of sensitivity
      analyses. CONCLUSION: The sNPWT can be considered a cost saving intervention that
      reduces surgical site complications following CABG surgery compared to standard
      care. We however recommend that additional economic studies should be conducted
      as new evidence on the use of sNPWT in CABG patients becomes available to
      validate the results of this economic analysis.

PMID- 30285809
TI  - Membrane associated collagen XIII promotes cancer metastasis and enhances anoikis
      resistance.
AB  - BACKGROUND: Increased collagen expression and deposition are associated with
      cancer progression and poor prognosis in breast cancer patients. However,
      function and regulation of membrane-associated collagen in breast cancer have not
      been determined. Collagen XIII is a type II transmembrane protein within the
      collagen superfamily. Experiments in tissue culture and knockout mouse models
      show that collagen XIII is involved in cell adhesion and differentiation of
      certain cell types. In the present study, we determined roles of collagen XIII in
      breast cancer progression and metastasis. METHODS: We analyzed the association of
      collagen XIII expression with breast cancer development and metastasis using
      published gene expression profiles generated from human breast cancer tissues.
      Utilizing gain- and loss- of function approaches and 3D culture assays, we
      investigated roles of collagen XIII in regulating invasive tumor growth. Using
      the tumorsphere/mammosphere formation assay and the detachment cell culture
      assay, we determined whether collagen XIII enhances cancer cell stemness and
      induces anoikis resistance. We also inhibited collagen XIII signaling with beta1
      integrin function-blocking antibody. Finally, using the lung colonization assay
      and the orthotopic mammary tumor model, we investigated roles of collagen XIII in
      regulating breast cancer colonization and metastasis. Cox proportional hazard
      (log-rank) test, two-sided Student's t-test (two groups) and one-way ANOVA (three
      or more groups) analyses were used in this study. RESULTS: Collagen XIII
      expression is significantly higher in human breast cancer tissue compared with
      normal mammary gland. Increased collagen XIII mRNA levels in breast cancer tissue
      correlated with short distant recurrence free survival. We showed that collagen
      XIII expression promoted invasive tumor growth in 3D culture, enhanced cancer
      cell stemness, and induced anoikis resistance. Collagen XIII expression induced
      beta1 integrin activation. Blocking beta1 integrin activation significantly
      reduced collagen XIII-induced invasion and mammosphere formation. Importantly,
      silencing collagen XIII in MDA-MB-231 cells reduced lung colonization and
      metastasis. CONCLUSIONS: Our results demonstrate a novel function of collagen
      XIII in promoting cancer metastasis, cell invasion, and anoikis resistance.

PMID- 30285810
TI  - Lymphatic endothelial cells promote productive and latent HIV infection in
      resting CD4+ T cells.
AB  - BACKGROUND: An HIV cure has not yet been achieved because latent viral reservoirs
      persist, particularly in resting CD4+ T lymphocytes. In vitro, it is difficult to
      infect resting CD4+ T cells with HIV-1, but infections readily occur in vivo.
      Endothelial cells (EC) line the lymphatic vessels in the lymphoid tissues and
      regularly interact with resting CD4+ T cells in vivo. Others and we have shown
      that EC promoted productive and latent HIV infection of resting CD4+ T cells.
      However, the EC used in previous studies were from human umbilical cords (HUVEC),
      which are macrovascular; whereas EC residing in the lymphoid tissues are
      microvascular. METHODS: In this study, we investigated the effects of
      microvascular EC stimulation of resting CD4+ T cells in establishing viral
      infection and latency. Human resting and activated CD4+ T cells were cultured
      alone or with endothelial cells and infected with a pseudotyped virus. Infection
      levels, indicated by green fluorescent protein expression, were measured with
      flow cytometry and data was analyzed using Flowing Software and Excel. RESULTS:
      We confirmed that EC from lymphatic tissue (LEC) were able to promote HIV
      infection and latency formation in resting CD4+ T cells while keeping them in
      resting phenotype, and that IL-6 was involved in LEC stimulation of CD4+ T cells.
      However, there are some differences between stimulation by LEC and HUVEC. Unlike
      HUVEC stimulation, we demonstrated that LEC stimulation of resting memory T cells
      does not depend on major histocompatibility complex class II (MHC II)
      interactions with T cell receptors (TCR) and that CD2-CD58 interactions were not
      involved in LEC stimulation of resting T cells. LEC also secreted lower levels of
      IL-6 than HUVEC. We also found that LEC stimulation increases HIV infection rates
      in activated CD4+ T cells. CONCLUSIONS: While differences in T cell stimulation
      between lymphatic EC and HUVEC were observed, we confirmed that similar to
      macrovascular EC stimulation, microvascular EC stimulation promotes direct HIV
      infection and latency formation in resting CD4+ T cells without T cell
      activation. LEC stimulation also increased infection rates in activated CD4+ T
      cells. Additionally, the present study established a physiologically more
      relevant model of EC interactions with resting CD4+ T cells and further
      highlighted the importance of investigating the roles of EC in HIV infection and
      latency in both resting and activated CD4+ T cells.

PMID- 30285813
TI  - Long-term clinical outcomes in patients with viral hepatitis related liver
      cirrhosis after transjugular intrahepatic portosystemic shunt treatment.
AB  - BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) procedure has
      played a vital role in management of portal hypertension. Thus, we aimed to
      investigate the natural history, long-term clinical outcome, predictors of
      survival in viral hepatitis related cirrhotic patients post-TIPS. METHOD: A total
      of 704 patients with complete followed-up data were enrolled, and clinical
      characteristics of patients were collected and analyzed. Kaplan-Meier method was
      used to calculate survival, and comparisons were made by log rank test. A
      multivariate analysis of factors influencing survival was carried out using the
      Cox proportional hazards regression model. RESULTS: TIPS implatantion
      significantly decreased portal vein pressure with 9.77 cmH2O reduction, without
      influencing long-term liver functions. The total incidence rate of major
      complication post-TIPS, including HE and re-bleeding/bleeding, was 37.9% and
      15.5%, respectively. Patients in Child-Pugh C stage revealed higher overt hepatic
      encephalopathy (HE) occurrence (65.6%), while patients receiving covered, 6 mm in
      diameter stents indicated notably lower incidence of HE in comparison with other
      groups (6.4%). The median survival was > 60 months, 27.0 months, and 11.5 months
      in cirrhotic patients with variceal bleeding, refractory ascites, and both
      complications, respectively. The cumulative 5-year survival was significantly
      higher in patients with variceal bleeding (75.6%) in comparison with either that
      in patients with refractory ascites (12.5%) or that in patients with both
      complications (1.96%) (P < 0.0001). Covered stents usage, baseline model for end
      stage liver disease (MELD) score, and baseline Child-Pugh classification were
      predictive of survival (P < 0.001). Other variables including age, male gender,
      and pre-TIPS PVP were not emerged as significant predictors (P > 0.05).
      CONCLUSION: TIPS was an effective and safe therapeutic method for decompression
      of portal hypertension and for treatment of its complications. Careful selection
      of patients with minimal liver dysfunction for TIPS implantation was essential
      for better long-term outcomes.

PMID- 30285812
TI  - A novel model to correlate hydrogel spacer placement, perirectal space creation,
      and rectum dosimetry in prostate stereotactic body radiotherapy.
AB  - BACKGROUND: The SpaceOAR hydrogel is employed to limit rectal radiation dose
      during prostate radiotherapy. We identified a novel parameter - the product of
      angle theta and hydrogel volume - to quantify hydrogel placement. This parameter
      predicted rectum dosimetry and acute rectal toxicity in prostate cancer patients
      treated with stereotactic body radiotherapy to 36.25 Gy in 5 fractions. METHODS:
      Twenty men with low- and intermediate-risk prostate cancer underwent hydrogel
      placement from 2015 to 2017. Hydrogel symmetry was assessed on the CT simulation
      scan in 3 axial slices (midgland, 1 cm above midgland, 1 cm below midgland). Two
      novel parameters quantifying hydrogel placement - hydrogel volume and angle theta
      formed by the prostate, hydrogel, and rectum - were measured, and the normalized
      product of theta and hydrogel volume calculated. These were then correlated with
      perirectal distance, rectum maximum 1-3 cc point doses (rDmax 1-3 cc), and rectum
      volumes receiving 80-95% of the prescription dose (rV80-95%). Acute rectal
      toxicity was recorded per RTOG criteria. RESULTS: In 50% of patients, hydrogel
      placement was symmetric bilaterally to within 1 cm of midline in all three CT
      simulation scan axial slices. Lateral hydrogel asymmetry < 2 cm in any one axial
      slice did not affect rectum dosimetry, but absence of hydrogel in the inferior
      axial slice resulted in a mean increase of 171 cGy in the rDmax 1 cc (p < 0.005).
      The perirectal distance measured at prostate midgland, midline (mean 9.1 +/- 4.3
      mm) correlated strongly with rV95 (R2 0.6, p < 0.001). The mean hydrogel volume
      and theta were 10.3 +/- 4.5 cc and 70 +/- 49 degrees , respectively. Perirectal
      distance, rV95 and rDmax 1 cc correlated with hydrogel angle theta (p < 0.01),
      and yet more strongly with the novel metric theta*hydrogel volume (p < 0.001).
      With a median follow up of 14 months, no rectal toxicity >grade 2 was observed.
      Low grade rectal toxicity was observed in a third of men and resolved within 1
      month of SBRT. Men who had these symptoms had higher rDmax 1 cc and smaller
      theta*hydrogel volume measurements. CONCLUSIONS: Optimal hydrogel placement
      occurs at prostate midgland, midline. The novel parameter theta*hydrogel volume
      describes a large proportion of rectum dosimetric benefit derived from hydrogel
      placement, and can be used to assess the learning curve phenomenon for hydrogel
      placement.

PMID- 30285815
TI  - Impact of graft and tunnel orientation on patient-reported outcome in anterior
      cruciate ligament reconstruction using bone-patellar tendon-bone autografts.
AB  - BACKGROUND: The optimal positioning of anterior cruciate ligament graft is still
      controversially discussed. We therefore wanted to determine the tunnel-to-joint
      (TJA), tunnel-to-shaft (TSA), and graft-tunnel divergence angles which would
      provide the best outcome, determined by the KOOS (Knee Injury and Osteoarthritis
      Outcome Score). This study evaluated the clinical influence of graft orientation
      as measured with the KOOS questionnaire in patients with anterior cruciate
      ligament reconstruction with bone-patellar tendon-bone autografts. METHODS: We
      designed a prospective cohort study, with a 1 1/4 year recruitment phase from
      March 2011 to July 2012 and a minimal follow-up period of 1 year. Inclusion
      criteria were patients >= 18 years of age receiving an ACL reconstruction with
      bone-patellar tendon-bone autografts at our institution after having suffered an
      acute ACL rupture. The primary outcome was the KOOS. Independent variables were
      patient age, gender, laterality of rupture, mechanism of trauma, and type of
      femoral and tibial fixation, as well as sagittal graft-tunnel divergence, TJA,
      and TSA, the latter two being assessed on coronal slices of magnetic resonance
      imaging. Equations modeling the relationship between TJA, TSA, and graft-tunnel
      divergence with the KOOS overall score were fitted, and the optimum angles were
      mathematically determined. RESULTS: In total, 31 patients were included in our
      study. Our cohort with a median age of 28 years was predominantly male. The
      mathematically determined optimal placement of the implant in the coronal plane
      was a TJA of 74.8 degrees , a TSA of 80.1 degrees , and a graft-tunnel divergence
      angle of 8.5 degrees . CONCLUSION: With regard to patient-reported outcome, the
      optimal graft orientation is provided by a coronal tunnel-to-shaft angle of 80
      degrees  and tunnel-to-joint angle of 75 degrees , respectively. Interestingly,
      in our series, patients reported best clinical outcomes with a sagittal graft
      tunnel divergence. These results should be validated in larger studies.

PMID- 30285814
TI  - Can a brief psychological intervention improve oral health behaviour? A
      randomised controlled trial.
AB  - BACKGROUND: Dental caries is a major public health issue affecting a large
      proportion of the general population. The disease is associated with behavioural
      factors and is thus preventable to a high degree. Individuals may need assistance
      to be able to change their oral health behaviour. There is a lack of such
      interventions for adults affected by severe caries. The aim of the study was to
      evaluate the effect of Acceptance and Commitment Therapy (ACT), a form of
      cognitive behavioural therapy, on oral health behaviour in young adults with poor
      oral health. METHODS: The study included a two group parallel randomised
      controlled trial at general dental clinics, with young adults, 18-25 years of
      age, >= two manifest proximal dental caries lesions (n = 135); 67 were treated
      with ACT and 68 with standard disease information only, respectively. Primary
      outcomes: oral health behaviours (tooth-brushing, flossing, use of toothpicks,
      and additional fluoride use). The CONSORT principles for RCTs were used,
      including intention-to-treat and per protocol analyses. The Chi-square, Mann
      Whitney, and Wilcoxon Signed Rank tests were applied, including effect sizes.
      RESULTS: The study groups did not differ with regard to oral health behaviour
      variables at baseline. The intervention group improved all their oral health
      behaviours significantly over time (effect sizes, 0.26-0.32), while the control
      group showed improved behaviours on two measures (flossing and additional use of
      fluoride, effect sizes, 0.22-0.23). CONCLUSIONS: By testing a psychological
      intervention on young adults (18-25 years of age) with a high prevalence of
      caries, we found an immediate positive effect with improved oral health
      behaviours. TRIAL REGISTRATION: TRN ISRCTN15009620 , retrospectively registered
      14/03/2018.

PMID- 30285816
TI  - Urea cycle disorders in India: clinical course, biochemical and genetic
      investigations, and prenatal testing.
AB  - BACKGROUND: Urea cycle disorders (UCDs) are inherited metabolic disorders that
      present with hyperammonemia, and cause significant mortality and morbidity in
      infants and children. These disorders are not well reported in the Indian
      population, due to lack of a thorough study of the clinical and molecular
      profile. RESULTS: We present data from two major metabolic centres in India,
      including 123 cases of various UCDs. The majority of them (72/123, 58%) presented
      in the neonatal period (before 30 days of age) with 88% on or before day 7 of
      life (classical presentation), and had a high mortality (64/72, 88%).
      Citrullinemia type 1 was the most common UCD, observed in 61/123 patients.
      Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24
      cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of
      arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and
      lysinuric protein intolerance were also observed. Molecular genetic analysis
      revealed two common ASS1 mutations: c.470G > A (p.Arg157His) and c.1168G > A
      (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point
      mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A
      total of 24 novel mutations were observed in the various genes studied. We
      observed a poor clinical outcome with an overall all time mortality of 63%
      (70/110 cases with a known follow-up), and disability in 70% (28/40) among the
      survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families,
      including one pre-implantation genetic diagnosis. CONCLUSIONS: We report the
      occurrence of UCDs in India and the spectrum that may be different from the rest
      of the world. Citrullinemia type 1 was the most common UCD observed in the
      cohort. Increasing awareness amongst clinicians will improve outcomes through
      early diagnosis and timely treatment. Genetic diagnosis in the proband will
      enable prenatal/pre-implantation diagnosis in subsequent pregnancies.

PMID- 30285817
TI  - Assessment of the effect of the corticotomy-assisted orthodontic treatment on the
      maxillary periodontal tissue in patients with malocclusions with transverse
      maxillary deficiency: a case series.
AB  - BACKGROUND: The aim of the study was to assess the effect of corticotomy-assisted
      orthodontic treatment on soft tissue clinical parameters in patients with
      malocclusions with transverse maxillary deficiency. METHODS: The study included
      20 generally healthy adult individuals with malocclusion, who underwent a
      corticotomy-assisted orthodontic treatment in maxilla. During the corticotomy
      performed after full-thickness flap elevation, only the buccal cortical plate was
      cut with the use of OTS-7, OTS7-4, OTS7-3 ultrasound tips of the piezosurgery
      device (Mectron s. p. a., Italy). A clinical examination was performed prior to
      the corticotomy procedure, then repeated - 3, 6, 9 and 12 months after the
      procedure. The following parameters were assessed: FMPI (full mouth plaque
      index), FMBOP (full mouth bleading on probing), PD (probing depth), CAL (clinical
      attachment level), GR (gingival recession height), RW (recession width), PH
      (papilla height), PW (papilla width), BS (bone sounding), biotype and KT.
      RESULTS: There was a statistically significant reduction in PD (mean difference:
      0.06; 95% Cl: - 0.33, - 0.18), CAL (mean difference: 0.07; 95% Cl: - 0.33, -
      0.19), PH (mean difference: 0.26; 95% Cl: - 0.47, 0.05) and BS (mean difference:
      0.13; 95% Cl: - 0.41, - 0.14) after the treatment. Statistically significant
      changes were also noted in relation to KT (mean difference: 0.17; 95% Cl: - 0.07,
      0.27) and biotype (mean difference: 0.07; 95% Cl: 0.26, 0.39), which thickness
      increased significantly after the treatment. No statistically significant
      differences were observed in GR, RW and PW. CONCLUSIONS: The corticotomy-assisted
      orthodontic treatment did not jeopardize the periodontal clinical status in
      maxilla. There is a need for further studies on a larger number of patient to
      compare the clinical findings with a control group as well as in patients with
      conventional orthodontic treatment in a longer follow-up time to find out more
      about the post-treatment periodontal tissue changes and stability.

PMID- 30285819
TI  - Correction to: China's health assistance to Africa: opportunism or altruism?
AB  - Please note that following publication of the original article [1], one of the
      authors has flagged that the abbreviations section lists "BRIC" as "Britain,
      Russia, India and China".

PMID- 30285818
TI  - Physician experience with speech recognition software in psychiatry: usage and
      perspective.
AB  - OBJECTIVE: The purpose of this paper is to extend a previous study by evaluating
      the use of a speech recognition software in a clinical psychiatry milieu.
      Physicians (n = 55) at a psychiatric hospital participated in a limited
      implementation and were provided with training, licenses, and relevant devices.
      Post-implementation usage data was collected via the software. Additionally, a
      post-implementation survey was distributed 5 months after the technology was
      introduced. RESULTS: In the first month, 45 out of 51 (88%) physicians were
      active users of the technology; however, after the full evaluation period only
      53% were still active. The average active user minutes and the average active
      user lines dictated per month remained consistent throughout the evaluation. The
      use of speech recognition software within a psychiatric setting is of value to
      some physicians. Our results indicate a post-implementation reduction in
      adoption, with stable usage for physicians who remained active users. Future
      studies to identify characteristics of users and/or technology that contribute to
      ongoing use would be of value.

PMID- 30285820
TI  - Factors associated with high-risk human papillomavirus test utilization and
      infection: a population-based study of uninsured and underinsured women.
AB  - BACKGROUND: Current cervical cancer screening guidelines recommend a Pap test
      every 3 years for women age 21-65 years, or for women 30-65 years who want to
      lengthen the screening interval, a combination of Pap test and high-risk human
      papilloma virus testing (co-testing) every 5 years. Little population-based data
      are available on human papilloma virus test utilization and human papilloma virus
      infection rates. The objective of this study was to examine the patient-level,
      cervical cancer screening, and area-level factors associated with human papilloma
      virus testing and infection among a diverse sample of uninsured and underinsured
      women enrolled in the New Jersey Cancer Early Education and Detection (NJCEED)
      Program. METHODS: We used data for a sample of 50,510 uninsured/underinsured
      women, age >= 29 years, who screened for cervical cancer through NJCEED between
      January 1, 2009 and December 31, 2015. Multivariable logistic regression models
      were used to estimate associations between ever having a human papilloma virus
      test or a positive test result, and individual- (age, race/ethnicity, birthplace)
      and area-level covariates (% below federal poverty level, % minority, %
      uninsured), and number of screening visits. RESULTS: Only 26.6% (13,440) of the
      sample had at least one human papilloma virus test. Among women who underwent
      testing, 13.3% (1792) tested positive for human papilloma virus. Most women who
      were positive for human papilloma virus (99.4%) had their first test as a co
      test. Human papilloma virus test utilization and infection were significantly
      associated with age, race/ethnicity, birthplace (country), and residential area
      level poverty. Rates of human papilloma virus testing and infection also differed
      significantly across counties in the state of New Jersey. CONCLUSIONS: These
      findings suggest that despite access to no-cost cervical cancer screening for
      eligible women, human papilloma virus test utilization was relatively low among
      diverse, uninsured and underinsured women in New Jersey, and test utilization and
      infection were associated with individual-level and area-level factors.

PMID- 30285821
TI  - Significant reductions in tertiary hospital encounters and less travel for
      families after implementation of Paediatric Care Coordination in Australia.
AB  - BACKGROUND: Over a third of Australian children have long-term health conditions,
      often involving multiple organ systems and resulting in complex health care
      needs. Our healthcare system struggles to meet their needs because of sectoral
      fragmentation and episodic models of care. Children with medical complexity (CMC)
      currently rely on tertiary paediatric hospitals for most of their healthcare, but
      this is not sustainable. We evaluated the impacts of Care Coordination on
      tertiary hospital service use and family outcomes. METHODS: A pre- and post
      implementation cohort evaluation of the Care Coordination service at a tertiary
      paediatric hospital network, was undertaken. From July 2015 CMC enrolled in the
      service had access to a Care Coordinator, shared-care plans, linkage with local
      general practitioners (GPs), and access to a 24-h Hotline from August 2016. CMC
      were those with >=4 emergency department (ED) presentations, hospital stays of
      >=14 days, or >= 10 outpatient appointments in 12 months. Medically fragile
      infants at risk of frequent future hospital utilisation, and children with
      medical problems complicated by difficult family psychosocial circumstances were
      also included. Care Coordinators collected outcomes for each enrolled child.
      Administrative data on hospital encounters 6 months pre- and post-enrolment were
      analysed for children aged > 6 months. RESULTS: An estimated 557 hospital
      encounters, were prevented in the 6 months after enrolment, for 534 children aged
      > 6 months. ED presentations decreased by 40% (Chi2 = 37.95; P < 0.0001) and day
      only admissions by 42% (Chi2 = 7.54; P < 0.01). Overnight admissions decreased by
      9% but this was not significant. An estimated Au$4.9 million was saved over 2
      years due to prevented hospital encounters. Shared-care plans were developed for
      83.5%. Of 84 children who had no regular GP, 58 (69%) were linked with one. Fifty
      five (10%) of families were linked to the 24-h Hotline to enable remote access to
      support and advice. Over 50,000 km of family travel and 370 school absences was
      prevented. CONCLUSIONS: The Care Coordination service has clear benefits for the
      tertiary paediatric hospital network and for families. Ongoing evaluation is
      essential for continuous improvement and to support adjustments to the model
      according to the local context.

PMID- 30285824
TI  - Spatial relationships among public places frequented by families plagued by
      methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVE: To understand factors associated with community-associated methicillin
      resistant Staphylococcus aureus (CA-MRSA) acquisition and infection, we mapped
      public places (including personal service establishments, fitness centers, pools,
      schools, and daycares) visited by members of households affected by CA-MRSA skin
      and soft tissue infection. RESULTS: From January 2012 to October 2015, households
      of children with CA-MRSA SSTI in metropolitan St. Louis were enrolled in the
      HOME: Household Observation of MRSA in the Environment study. Addresses of public
      places visited within 3 months of enrollment were reported by 671 participants
      and were analyzed using a geographic information system (GIS). The Nearest
      Neighbor Tool in ArcGIS assessed clustering of public places within the study
      region. Public places were significantly clustered within the study area compared
      to the expected distance between locations (p < 0.001). Additionally, one-third
      (48/150) of participating households visited at least one public place in common
      with other households. No significant relationship between participants visiting
      the public places within 3 months of enrollment and subsequent colonization or
      SSTI were found. Understanding community behavior is critical to informing public
      health initiatives to reduce the prevalence of CA-MRSA infections.

PMID- 30285822
TI  - Association between brain-derived neurotrophic factor gene polymorphisms and
      fibromyalgia in a Korean population: a multicenter study.
AB  - BACKGROUND: Several lines of evidence imply that brain-derived neurotrophic
      factor (BDNF) is involved in the pathophysiology of fibromyalgia (FM); in this
      regard, patients with FM have altered blood and cerebrospinal fluid levels of
      BDNF. In this study, we explored the association between BDNF gene polymorphisms
      and FM susceptibility and the severity of symptoms. METHODS: In total, 409
      patients with FM and 423 healthy controls in 10 medical centers were enrolled
      from the Korean nationwide FM survey. The alleles and genotypes at 10 positions
      in the BDNF gene were genotyped. RESULTS: The allele and genotype frequencies of
      BDNF rs11030104 differed significantly between the patients with FM and the
      controls (P = 0.031). The GG genotype of rs11030104 had a protective effect
      against FM (P = 0.016), and the G allele of rs11030104 was negatively associated
      with the presence of FM compared with the A allele (P = 0.013). In comparison,
      although the allele and genotype frequencies of BDNF rs12273539 did not differ
      between the two groups, the TT genotype of BDNF rs12273539 was associated with
      susceptibility to FM (P = 0.038). Haplotype analyses implied that some BDNF
      haplotypes have a protective effect against FM. Finally, several genotypes and
      haplotypes of the BDNF gene contributed to specific symptoms of FM. CONCLUSIONS:
      This study is the first to evaluate the associations between BDNF gene
      polymorphisms and FM. Our results imply that some BDNF single-nucleotide
      polymorphisms and haplotypes are associated with susceptibility to, and
      contribute to the symptoms of, FM.

PMID- 30285823
TI  - A web-based education program to encourage organ donation registration among
      lower-educated adolescents in the Netherlands: study protocol for a cluster
      randomized controlled trial.
AB  - BACKGROUND: The gap between the supply and demand of organ donors is substantial,
      causing patients to suffer from long waiting times. Moreover, the lack of
      registrations places a burden on family members and medical professionals when an
      unregistered individual dies. This article describes a cluster randomized
      controlled trial (CRCT) study to assess the effectiveness and quality of
      implementation of a web-based program aimed at encouraging lower-educated
      adolescents to register a well-informed choice about organ donation, regardless
      of it being as a donor or not. METHODS/DESIGN: The program will be delivered by
      teachers at schools for Intermediate Vocational Education in the Netherlands. The
      effectiveness will be assessed in a CRCT design with post-test only using self
      administered questionnaires for the primary outcome (i.e. intention to register).
      Classes will be matched to improve equivalence of groups. From each pair of
      matched classes, one class will be randomly assigned to the experimental
      condition, and the other assigned to the control condition. Students in the
      control groups will fill in the questionnaire before receiving the program, while
      the experimental groups will do this afterwards. A post-test design prevents the
      risk of testing bias. The required sample size is 14 schools, with 10 classes per
      school and 13 unregistered students per class. The questionnaire assesses
      demographics, behavioural determinants (attitude, self-efficacy, knowledge and
      social outcomes), intention to register (as a donor) and registration status. Six
      months after delivery, registration status will be assessed again. Additionally,
      a process evaluation will be conducted to evaluate the quality of implementation
      using both qualitative (i.e. semi-structured interviews) and quantitative (i.e.
      logbooks, questionnaires, Google Analytics to track user behaviour at the
      website) methods. DISCUSSION: Findings of the study can help to further improve
      the program and serve as a basis for a solid dissemination plan. Moreover, the
      study will provide insight into (change in) determinants of registration and
      donorship and the translation of research into practice of school-based health
      promotion interventions, which can serve as an example for others. TRIAL
      REGISTRATION: The Dutch Trial Register, NTR6771 . Registered on 24 October 2017.
      This is version 2 of the protocol (5 November 2017).

PMID- 30285825
TI  - The feasibility of following up prisoners, with mental health problems, after
      release: a pilot trial employing an innovative system, for engagement and
      retention in research, with a harder-to-engage population.
AB  - BACKGROUND: Following up released prisoners is demanding, particularly for those
      prisoners with mental health problems, for whom stigma and chaotic lifestyles are
      problematic. Measurement of mental health outcomes after release is challenging.
      To evaluate mental healthcare for offender populations, using high-quality
      randomised controlled trials, evidenced-based methods must be developed to engage
      them while in custody, to locate and re-interview them after release, and to
      collect potentially stigmatising mental health outcomes data. METHODS: We
      developed an initial theoretical model and operational procedures for collecting
      baseline and follow-up data informed by a literature search, focus groups, and
      case studies. Male prisoners from five prisons in two sites were invited to
      participate. The inclusion criteria included individuals who were above threshold
      on nine-item Patient Health Questionnaire, seven-item Generalized Anxiety
      Disorder, or post-traumatic stress disorder scales, or who had reported mental
      health problems in the past 2 years or had been assessed with a likely
      personality disorder. Potential participants were interviewed to generate
      baseline data and were re-contacted before their release. We then contacted them
      for a follow-up interview, which included repeating the earlier data collection
      measures 2-8 weeks after release. A qualitative formative process evaluation
      produced and refined a model procedure for the recruitment and retention of male
      prison leavers in trials, identified the mechanisms which promoted engagement and
      retention, and mapped these against a theoretical behaviour change model.
      RESULTS: We developed a flexible procedure which was successful in recruiting
      male prison leavers to a pilot trial: 185/243 (76%, 95% confidence interval (CI)
      70-81%) of those approached agreed to participate. We also retained 63% (95% CI
      54-71%) of those eligible to participate in a follow-up interview 2-8 weeks after
      release. Mental health outcomes data was collected at both these time points.
      CONCLUSIONS: It is possible to design acceptable procedures to achieve sustained
      engagement critical for delivering and evaluating interventions in prison and in
      the community and to collect mental health outcomes data. These procedures may
      reduce attrition bias in future randomised controlled trials of mental health
      interventions for prison leavers. This procedure has been replicated and
      successfully delivered in a subsequent pilot trial and a definitive randomised
      controlled trial.

PMID- 30285826
TI  - The clinician-scientist track: an approach addressing Australia's need for a
      pathway to train its future clinical academic workforce.
AB  - BACKGROUND: Clinician-scientist training represents the epitome of preparation
      for biomedical scientific discovery. The significance of, and need for, clinician
      scientists is universally recognised as essential to progress medical research
      across what is regarded as the 'translational gap'. Despite a rich history of
      cutting-edge biomedical research, Australia has no infrastructure or career
      pathway for training clinician-scientists. DISCUSSION: The Clinician-scientist
      Track (CST) was developed to address this concern at the University of
      Queensland. The CST concept began in 2010 with the Concurrent MD-Masters that
      allowed students to undertake a research Masters concurrently with their medical
      program. The rationale was to offer an attractive and realistic option to recruit
      our highest performing students into a research higher degree, with the
      underlying aim of encouraging those most capable, to transfer to the MD-PhD. The
      Concurrent MD-Masters was immediately popular and remains so. Over 8 years,
      enrolments rose seven-fold (60 MD-Masters, 36 MD-PhDs). The transfer rate from MD
      Masters to MD-PhD is 28% supporting our original aim. CONCLUSIONS: Many
      challenges remain for the future of the program. These challenges are underpinned
      by a culture that values clinician-scientists as crucial to ensuring that high
      quality health and medical research is undertaken and translated to patient care,
      but lags behind in establishing an infrastructure to develop and maintain a new
      generation of this vital workforce. A future challenge is to develop a
      coordinated approach to a supported Australian MD-PhD pathway for our most
      talented and committed students beginning in the undergraduate Bachelor's degree
      into the medical degree and throughout specialty training. Shared responsibility
      is necessary between institutions and stakeholders to support and nurture newly
      trained MD-PhDs into the post-graduate years. Flexibility across this medical
      training continuum that allows integration of both degrees will help ensure
      students make the most meaningful connections between the research and the
      medicine. What is paramount will be acknowledging the career expectations of an
      emerging cohort of medical students, in particular females, wishing to pursue
      research. Without these considerations we risk losing our next generation of
      potential clinician-scientists.

PMID- 30285827
TI  - Dietary factors associated with preeclampsia or eclampsia among women in delivery
      care services in Addis Ababa, Ethiopia: a case control study.
AB  - OBJECTIVE: Preeclampsia or eclampsia, which is one of the direct obstetric
      complication, results in maternal and child morbidity and mortality. The factors
      associated with it remains unclear. So, the aim of the study was to assess the
      dietary factors associated with preeclampsia or eclampsia among women in delivery
      care services in Addis Ababa, Ethiopia. RESULTS: Factors which were investigated
      as protective for preeclampsia or eclampsia were: Fruit intake during pregnancy
      (AOR: 0.94, 95% CI 0.20, 4.32), vegetable intake during pregnancy (AOR: 0.95, 95%
      CI 0.01, 0.71) and receiving nutritional counseling during antenatal care (AOR:
      0.17, 95% CI 0.05, 0.6). In the other side being nulliparous women was a risk
      factor for preeclampsia or eclampsia (AOR: 2.02, 95% CI 1.15, 3.55).

PMID- 30285828
TI  - Influence of HLA-B27 on the Ankylosing Spondylitis phenotype: results from the
      REGISPONSER database.
AB  - OBJECTIVE: To assess HLA-B27 influence on the clinical phenotype of Ankylosing
      Spondylitis (AS) patients. METHOD: An observational, cross-sectional and
      descriptive study of AS patients from the Spanish REGISPONSER database was
      performed. Demographic, clinical, disease activity (Bath Ankylosing Spondylitis
      Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index
      (BASFI), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)), and
      radiographic data (Bath Ankylosing Spondylitis Radiology Index (BASRI) score)
      were compared regarding HLA-B27 status. A univariate and multivariate analysis
      was performed to identify variables independently related to the presence of HLA
      B27. RESULTS: Data from 1235 patients (74.8% male) were analyzed; 1029 were HLA
      B27 positive (83%). HLA-B27-positive patients showed higher family aggregation
      and an earlier onset of disease compared with those who were HLA-B27 negative.
      HLA-B27-negative patients presented statistically higher BASDAI and BASFI scores
      and higher prevalence of arthritis, dactylitis, and extra-articular
      manifestations (psoriasis and inflammatory bowel disease (IBD)) but not anytime
      uveitis compared with those who were HLA-B27 positive. In the multivariate
      analysis, family history (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.27
      3.49), younger age at diagnosis (OR 0.97, 95% CI 0.96-0.98), presence of
      peripheral arthritis (OR 0.53, 95% CI 0.32-0.89), dactylitis (OR 0.16, 95% CI
      0.05-0.56), psoriasis (OR 0.45, 95% CI 0.26-0.78), and IBD (OR 0.22, 95% CI 0.12
      0.40) were the main variables independently related to the presence or not of HLA
      B27. CONCLUSION: In Caucasian AS patients, the presence of HLA-B27 is related to
      an earlier disease onset and higher family aggregation. Absence of HLA-B27 is
      related to a higher frequency of peripheral arthritis, dactylitis, and extra
      articular manifestations. Being HLAB27 positive is not related to a higher burden
      of disease or anytime uveitis.

PMID- 30285830
TI  - Late presentation, MR imaging features and surgical treatment of Herlyn-Werner
      Wunderlich syndrome (classification 2.2); a case report.
AB  - BACKGROUND: Herlyn-Werner-Wunderlich syndrome is a very rare congenital
      genitourinary anomaly characterized by uterus didelphys, blind hemivagina and
      ipsilateral renal agenesis. CASE PRESENTATION: Authors present a case of Herlyn
      Werner-Wunderlich syndrome in a 19-year-old unmarried woman who presented with
      pelvic pain and pelvic mass. MR imaging revealed the typical features of
      didelphys uterus, obstructed right hemivagina and ipsilateral renal agenesis. The
      patient subsequently underwent surgery. CONCLUSIONS: Herlyn-Werner-Wunderlich
      syndrome would be suspected in patients with unilateral absent kidney and pelvic
      mass. Ultrasonography and MR imaging can well depict the disease entity and
      surgery is the treatment of choice for obstructed hemivagina.

PMID- 30285829
TI  - CYLD suppression enhances the pro-inflammatory effects and hyperproliferation of
      rheumatoid arthritis fibroblast-like synoviocytes by enhancing NF-kappaB
      activation.
AB  - BACKGROUND: Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) actively
      drive joint inflammation and degradation by producing inflammatory cytokines and
      matrix-degrading molecules, making them key factors in the pathogenesis of RA.
      Cylindromatosis (CYLD) is a tumor suppressor that downregulates nuclear factor
      kappa-light-chain-enhancer of activated B cells (NF-kappaB) activation by
      deubiquitinating NF-kappaB essential modulator and tumor necrosis factor receptor
      associated factors 2 and 6. In this study, we aimed to determine CYLD expression
      in the synovium of patients with RA, analyze its correlation with NF-kappaB
      activation and clinical disease activity, further investigate CYLD expression in
      RA-FLSs, and explore CYLD's roles and mechanisms in the pro-inflammatory effects,
      proliferation, apoptosis, and cell cycles of RA-FLSs. METHODS: We obtained
      synovia from 50 patients with active RA and 20 with osteoarthritis (OA) and then
      cultured FLSs from the samples. We determined CYLD expression in the synovia of
      RA patients and in FLSs via reverse transcription polymerase chain reaction (RT
      PCR). CYLD was depleted by lentiviral CYLD short hairpin ribonucleic acid. We
      used RT-PCR and enzyme-linked immunosorbent assay to analyze the expression of
      pro-inflammatory cytokines, matrix metalloproteinases (MMPs), and receptor
      activator of nuclear factor kappa-B ligand (RANKL). We detected cell
      proliferation using Cell Counting Kit-8 and examined cell apoptosis and cell
      cycle using flow cytometry. RESULTS: We obtained the following results: 1. In
      synovia from patients with RA, CYLD expression was significantly downregulated
      while NF-kappaB expression was distinctly upregulated, compared with synovia from
      patients with OA. Thus, there is a significant inverse correlation between CYLD
      and NF-kappaB in synovia affected by RA. 2. CYLD expression significantly
      decreased in RA-FLSs compared with OA-FLSs. 3. CYLD suppression enhanced the
      production of pro-inflammatory cytokines, MMPs, and RANKL by activating NF-kappaB
      in RA-FLSs. 4. CYLD suppression enhanced proliferation, reduced apoptosis, and
      increased cell division of RA-FLSs and aggravated the activity of NF-kappaB in RA
      FLSs. CONCLUSIONS: Via its regulation of NF-kappaB activation, CYLD may be
      involved in the pathogenesis of synovial inflammation in RA as well as in the pro
      inflammatory effects and hyperproliferation of RA-FLSs. CYLD may therefore
      provide a potential target for the treatment of RA.

PMID- 30285831
TI  - Haemoglobin concentration following postpartum haemorrhage and the association
      between blood transfusion and breastfeeding: a retrospective cohort study.
AB  - OBJECTIVE: The aim of this study was to determine the association between red
      blood cell transfusion and breastfeeding among women who have suffered a
      postpartum haemorrhage at birth taking into account post-birth haemoglobin
      concentrations. RESULTS: Among 15,451 maternities with postpartum haemorrhage in
      New South Wales public hospitals between 2007 and 2010, 1828 (12%) received a red
      cell transfusion. Among transfused women, 686 (38%) had haemoglobin concentration
      pre-transfusion < 70 g/L, 792 (43%) had 70-90 g/L, and 350 (19%) had > 90 g/L.
      Rates and adjusted relative risks (aRR) for breastfeeding at hospital discharge
      were as follows: for women with haemoglobin concentrations < 70 g/L following
      birth and received a transfusion, 78.6% were breastfeeding and the aRR of
      breastfeeding compared to untransfused women was 0.90 (99% confidence interval
      (CI) 0.86-0.95); for women with haemoglobin concentrations 70-90 g/L, 81.3% were
      breastfeeding, aRR 0.94 (99% CI 0.90-0.98); and for women with haemoglobin
      concentrations > 90 g/L, 80.9% were breastfeeding, aRR 0.94 (99% CI 0.88-1.00).

PMID- 30285833
TI  - Intestinal parasitosis and associated factors among diabetic patients attending
      Arba Minch Hospital, Southern Ethiopia.
AB  - OBJECTIVE: Local assessment of the magnitude of intestinal parasitic infections
      and associated factors among diabetic patients helps for good prognosis of
      diabetes. Hospital based cross-sectional study was conducted by recruiting 215
      diabetic patients. A structured questionnaire was used to capture data about
      socio-demographic characteristics, clinical history and factors associated with
      intestinal parasitosis. Stool samples were collected and processed by direct wet
      mount, formol-ether concentration and modified ziehl-Neelson staining techniques.
      All data were analyzed using Statistical Package for Social Sciences software
      version 20. RESULTS: The rate of intestinal parasitic infection among diabetic
      patients was 19.5%. Cryptosporidium parvum accounts the highest frequency (18,
      8.4%) followed by Ascaris lumbricoides (8, 3.7%). Presence of domestic animals in
      the house (AOR = 2.857, 95% CI 1.290-6.330, p = 0.010), manifestation of
      abdominal pain (AOR = 3.716, 95% CI 1.632-8.459, p = 0.002) and farmer and labor
      occupation (AOR = 3.695, 95% CI 1.082-12.618, p = 0.037) were significantly
      associated with intestinal parasitosis. The magnitude of intestinal parasitosis
      among diabetic patients attending Arba Minch Hospital was considerable. Hence, we
      recommend routine screening and prompt treatment for intestinal parasitosis in
      order to improve the health of diabetic patients.

PMID- 30285832
TI  - Notch2 signal is required for the maintenance of canine hemangiosarcoma cancer
      stem cell-like cells.
AB  - BACKGROUND: Hemangiosarcoma (HSA) is a malignant tumor derived from endothelial
      cells which usually shows poor prognosis due to its high invasiveness, metastatic
      rate and severe hemorrhage from tumor ruptures. Since the pathogenesis of HSA is
      not yet complete, further understanding of its molecular basis is required.
      RESULTS: Here, we identified Notch2 signal as a key factor in maintaining canine
      HSA cancer stem cell (CSC)-like cells. We first cultured HSA cell lines in
      adherent serum-free condition and confirmed their CSC-like characteristics. Notch
      signal was upregulated in the CSC-like cells and Notch signal inhibition by a
      gamma-secretase inhibitor significantly repressed their growth. Notch2, a Notch
      receptor, was highly expressed in the CSC-like cells. Constitutive activation of
      Notch2 increased clonogenicity and number of cells which were able to survive in
      serum-free condition. In contrast, inhibition of Notch2 activity showed opposite
      effects. These results suggest that Notch2 is an important factor for maintaining
      HSA CSC-like cells. Neoplastic cells in clinical cases also express Notch2 higher
      than endothelial cells in the normal blood vessels in the same slides.
      CONCLUSION: This study provides foundation for further stem cell research in HSA
      and can provide a way to develop effective treatments to CSCs of endothelial
      tumors.

PMID- 30285835
TI  - Reduced fetal movement intervention Trial-2 (ReMIT-2): protocol for a pilot
      randomised controlled trial of standard care informed by the result of a
      placental growth factor (PlGF) blood test versus standard care alone in women
      presenting with reduced fetal movement at or after 36+ 0 weeks gestation.
AB  - BACKGROUND: Forty percent of babies who are stillborn born die after 36 weeks
      gestation and have no lethal structural abnormality. Maternal perception of
      reduced fetal movement (RFM) is associated with stillbirth and is related to
      abnormal placental structure and function. The ultimate objective of this trial
      is to assess whether for women with RFM, intervention directed by measurement of
      placental biochemical factors in addition to standard care improves pregnancy
      outcome compared with standard care alone. This is the protocol for a pilot trial
      to determine the feasibility of a definitive trial and also provide proof of
      concept that informing care by measurement of placental factors improves neonatal
      outcomes. METHODS: ReMIT-2 is a multicentre, pilot randomised controlled trial of
      care informed by results of an additional placental factor blood test versus
      standard care alone for women presenting with RFM at or after 36+ 0 weeks
      gestation. Participants will be randomised 1:1 to the intervention arm where the
      blood test result is revealed and acted on, or to the control arm where the blood
      sample is not tested immediately and therefore the result cannot be acted on. All
      participants will be followed up six weeks after delivery to assess their health
      status and views of the trial, along with healthcare costs. A sub-group will be
      interviewed within 16 weeks after delivery to further explore their views of the
      trial. Outcomes to determine feasibility of a definitive trial include number of
      potentially eligible women, proportion lost to follow-up, clinical
      characteristics at randomisation, reasons for non-recruitment, compliance with
      the trial intervention and views of participants and clinicians about the trial.
      Proof of concept outcomes include: rates of induction of labour; Caesarean birth;
      and a composite neonatal outcome of stillbirths and deaths before discharge, 5
      min Apgar score < 7, umbilical artery pH < 7.05 and admission to neonatal unit
      for > 48 h. DISCUSSION: Results from this pilot trial will help determine whether
      a large definitive trial is feasible. Such a study would provide evidence to
      guide management of women with RFM and reduce stillbirths. TRIAL REGISTRATION:
      ISRCTN Registry, ISRCTN12067514 . Registered on 8 September 2017.

PMID- 30285836
TI  - Functional validation of human-specific PowerPlex(r) 21 System (Promega, USA) in
      chimpanzee (Pan troglodytes).
AB  - OBJECTIVE: This study was aimed to test the PowerPlex(r) 21 System (Promega,
      USA), used for human identification applications for its positive cross-species
      applicability in Chimpanzees (Pan troglodytes) in order to identify heterologous
      STRs which can be used for individual identification, paternity testing,
      relatedness establishment and reconstruction of pedigrees and studbook records
      for captive and wild chimpanzee breeding populations. RESULTS: Of 21 STRs in
      PowerPlex(r) 21 System (Promega, USA), 19 loci amplified and found to be
      polymorphic. Locus Aml showed differential banding patterns in males and females
      similar to those seen for humans and correctly assigned sexes of known identity.
      Altogether, 58 different alleles were found with an average 3.05 +/- 0.28 alleles
      per locus. Mean observed (Ho), and expected heterozygosity (He) were 0.93 +/-
      0.03 and 0.52 +/- 0.05, respectively.

PMID- 30285834
TI  - Toward population specific and personalized treatment of Helicobacter pylori
      infection.
AB  - In the face of rising prevalence of antibiotic resistance, susceptibility testing
      to provide personalized treatment is recommended prior to eradication therapy for
      Helicobacter pylori (H. pylori). Yet, population specific treatment according to
      the local prevalence of antibiotic resistance may be an alternative if
      susceptibility testing is not available. In this article, we reviewed the global
      prevalence of primary antibiotic resistance and the efficacies of commonly used
      regimens in antibiotic susceptible and resistance strains. We then constructed a
      model to predict the efficacies of these regimens and proposed an algorithm to
      choose the optimal first-line and rescue therapies according to the prevalence of
      antibiotic resistance. Clarithromycin-based therapy (triple, sequential,
      concomitant, and hybrid therapies) for 14 days remains the treatment of choice in
      regions with low clarithromycin resistance (<=15%) and bismuth quadruple therapy
      may be an alternative therapy. In regions with high clarithromycin resistance (>
      15%), bismuth quadruple therapy is the treatment of choice and non-bismuth
      quadruple therapy may be an alternative. Either levofloxacin-based therapy or
      bismuth quadruple therapy may be used as second-line rescue therapy for patients
      fail after clarithromycin-based therapies, whereas levofloxacin-based therapy may
      be used for patients fail after bismuth quadruple therapy. Susceptibility testing
      or genotypic resistance should be determined after two or more eradication
      failures. However, empirical therapy according to prior medication history to
      avoid the empirical reuse of levofloxacin and clarithromycin may be an acceptable
      alternative after consideration of cost, patient preference, and accessibility.
      Rifabutin-based therapy for 14 days may serve as the fourth-line therapy. New
      antibiotics specific for H. pylori are highly anticipated.

PMID- 30285838
TI  - Detection of virus-specific polymeric immunoglobulin A in acute hepatitis A, C, E
      virus serum samples using novel chimeric secretory component.
AB  - OBJECTIVE: To conduct a proof-of-concept study on preferential binding of
      polymeric IgA (pIgA) using a novel recombinant rabbit/human chimeric secretory
      component (cSC) and preliminary assessment of the diagnostic potential of virus
      specific pIgA in discriminating acute hepatitis A, E, and C (HAV, HEV, HCV)
      patients and uninfected controls using an indirect enzyme-linked immunoassay.
      RESULTS: cSC binds > 0.06 MUg/ml of purified human and mouse pIgA with negligible
      cross-reactivity against IgM and IgA. Virus-specific pIgA was significantly
      higher in serum of acute HAV (n = 6) and HEV (n = 12) patients than uninfected
      samples (HEV: p < 0.001; HAV: p = 0.001), and had low correlation with virus
      specific IgM (HEV r: - 0.25, 95% CI - 0.88 to 0.71, p = 0.636; HAV r: 0.05, 95%
      CI - 0.54 to 0.60, p: 0.885). Anti-HCV pIgA peaked early in HCV seroconversion
      panels (n = 14), and was undetectable after 4 weeks post-primary bleed, even in
      ongoing infections, while serum anti-HCV IgA, IgG and IgM persisted. Patients
      with early acute HCV infection had significantly higher levels of anti-HCV pIgA
      compared to those with chronic infections (p < 0.01). The use of novel cSC
      demonstrates the presence of virus-specific pIgA in sera of patients with acute
      HAV, HEV, and HCV infection, and posits its potential utility as a diagnostic
      biomarker that warrants further validation on larger sample populations.

PMID- 30285839
TI  - Outcome measures in clinical trials of treatments for acute severe haemorrhage.
AB  - BACKGROUND: Acute severe haemorrhage is a common complication of injury,
      childbirth, surgery, gastrointestinal pathologies and other medical conditions.
      Bleeding is a major cause of death, but patients also die from non-bleeding
      causes, the frequency of which varies by the site of haemorrhage and between
      populations. Because patients can bleed to death within hours, established
      interventions inevitably take priority over randomisation into a trial. These
      circumstances raise challenges in selecting appropriate outcome measures for
      clinical trials of haemostatic interventions. MAIN BODY: We use data from three
      large randomised controlled trials in acute severe haemorrhage (CRASH-2, WOMAN
      and HALT-IT) to explore the strengths and limitations of outcome measures
      commonly used in trials of haemostatic treatments, including all-cause and cause
      specific mortality, blood transfusion and surgical interventions. Many deaths
      following acute severe haemorrhage are due to patient comorbidities or
      complications rather than bleeding. If non-bleeding deaths are unaffected by a
      haemostatic intervention, even large trials will have low power to detect an
      effect on all-cause mortality. Due to the dilution from deaths unaffected or
      reduced by the trial treatment, all-cause mortality can also obscure important
      harmful effects. Additionally, because the relative contributions of different
      causes of death vary within and between patient populations, all-cause mortality
      is not generalisable. Different causes of death occur at different time intervals
      from bleeding onset, with bleeding deaths generally occurring early. Time
      specific mortality can therefore be used as a proxy for cause in un-blinded
      trials where bias is a concern or in situations where cause of death cannot be
      assessed. Urgent treatment is critical, and so post-randomisation blood
      transfusion and surgery are often planned before or at the time of randomisation
      and therefore cannot be influenced by the trial treatment. CONCLUSIONS: All-cause
      mortality has low power, lacks generalisability and can obscure harmful effects.
      Cause-specific mortality, such as death due to bleeding or thrombosis, avoids
      these drawbacks. In certain scenarios, time-specific mortality can be used as a
      proxy for cause-specific mortality. Blood transfusion and surgical procedures
      have limited utility as outcome measures in trials of haemostatic treatments.

PMID- 30285840
TI  - Codon-optimized DsRed fluorescent protein for use in Mycobacterium tuberculosis.
AB  - OBJECTIVE: We have previously codon-optimized a number of red fluorescent
      proteins for use in Mycobacterium tuberculosis (mCherry, tdTomato, Turbo-635). We
      aimed to expand this repertoire to include DsRed, another widely used and
      flexible red fluorescent protein. RESULTS: We generated expression constructs
      with a full length DsRed under the control of one of three strong, constitutive
      promoters (Phsp60, PrpsA or PG13) for use in mycobacteria. We confirmed that full
      length DsRed (225 amino acids) was expressed and fluoresced brightly. In contrast
      to mCherry, truncated versions of DsRed lacking several amino acids at the N
      terminus were not functional. Thus, we have expanded the repertoire of optimized
      fluorescent proteins for mycobacteria.

PMID- 30285837
TI  - Leishmaniasis and glycosaminoglycans: a future therapeutic strategy?
AB  - Leishmania spp. depend on effective macrophage infection to establish and develop
      in mammalian hosts. Both metacyclic promastigotes and amastigotes are able to
      infect host cells, and thus they rely on several ligands that, when recognized by
      macrophage receptors, mediate parasite uptake. During macrophage primary
      infection with metacyclic forms from the insect vector and during amastigote
      dissemination via macrophage rupture, both infective stages have to cope with the
      host extracellular microenvironment, including extracellular matrix molecules.
      Glycosaminoglycans are abundant in the extracellular matrix and many of these
      molecules are able to interact with the parasite and the host cell, mediating
      positive and negative effects for the infection, depending on their structure
      and/or location. In addition, glycosaminoglycans are present at the surface of
      macrophages as proteoglycans, playing important roles for parasite recognition
      and uptake. In this review, we discuss glycosaminoglycans in the context of
      Leishmania infection as well as the possible applications of the current
      knowledge regarding these molecules for the development of new therapeutic
      strategies to control parasite dissemination.

PMID- 30285841
TI  - Increase of circulating memory B cells after glucocorticoid-induced remission
      identifies patients at risk of IgG4-related disease relapse.
AB  - BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) promptly responds to
      glucocorticoids but relapses in a considerable fraction of patients. Reliable
      biomarkers of flare are currently lacking because the pathophysiology of IgG4-RD
      remains largely elusive. In the present work, we aimed to identify perturbations
      of B-cell subpopulations that might predict IgG4-RD relapse. METHODS: Thirty
      patients were treated with glucocorticoids according to international guidelines.
      Circulating CD19+ and CD20+ cells, naive B cells, memory B cells, plasmablasts,
      and plasma cells were measured by flow cytometry at baseline and every 6 months
      for 2 years after the initiation of corticosteroid therapy. RESULTS: Patients
      with active untreated IgG4-RD showed significantly reduced CD19+ B cells, CD20+ B
      cells, and naive B cells compared with healthy subjects (p < 0.05), but
      significantly expanded plasmablasts and plasma cells (p < 0.01). After 6 months
      of corticosteroid treatment, all patients achieved clinical improvement. Naive B
      cells, plasmablasts, and plasma cells significantly decreased compared with
      disease onset, whereas memory B cells significantly increased compared with
      baseline (p < 0.01). Increase of memory B cells was observed only in patients who
      relapsed within 2 years of follow-up, however (HR, 12.24; 2.99 to 50.2; p =
      0.0005). In these patients, the relapse rates at 12 and 24 months were 30% and
      100%, respectively. No abnormalities of other B-cell subpopulations at disease
      onset or after 6 months of glucocorticoid treatment were found to predict IgG4-RD
      relapse at 2 years. CONCLUSIONS: Increase of circulating memory B cells after 6
      months of glucocorticoid treatment might predict IgG4-RD relapse.

PMID- 30285842
TI  - Are gender-specific approaches needed in diagnosing early axial
      spondyloarthritis? Data from the SPondyloArthritis Caught Early cohort.
AB  - BACKGROUND: Although gender differences have been observed in the severity of
      axial spondyloarthritis (axSpA), gender differences in disease presentation of
      early axSpA have not been thoroughly investigated. In particular, their impact on
      the diagnostic process is unknown. METHODS: Baseline data from the
      SPondyloArthritis Caught Early cohort, which includes patients with chronic back
      pain (CBP; duration >= 3 months and <= 2 years, age of onset < 45 years), were
      analysed. Patients underwent a full diagnostic work-up, including MRI and
      radiograph of the sacroiliac joints (MRI-SIJ and X-SIJ), to establish a diagnosis
      of axSpA. Characteristics of male and female patients with a certain diagnosis of
      axSpA (confidence level by the physician >= 7 on a 0-10 rating scale) were
      compared. Regression models were built for: the whole CBP cohort stratified by
      gender, to study which SpA features were associated most with diagnosis in each
      gender; and for axSpA patients, to test whether gender was associated with
      imaging positivity (MRI-SIJ+ and/or X-SIJ+). RESULTS: Of the 719 CBP patients,
      275 were male. With 146/275 males and 155/444 females diagnosed as axSpA, males
      were more likely to be diagnosed with axSpA (OR 2.1, 95% CI 1.5-2.9). Despite
      similar symptom duration, male axSpA patients were younger at diagnosis (27.4 +/-
      7.5 vs 29.5 +/- 7.8 years; p = 0.02). Presence of SpA features was similar in
      male and female axSpA patients, except for HLA-B27 and imaging positivity that
      were more common in male axSpA patients (80% vs 60%; p < 0.01 and 78% vs 64%; p =
      0.01). Nevertheless, these SpA features were still more prevalent in female axSpA
      patients than in no-axSpA patients, both females (HLA-B27+ 23%, positive imaging
      7%) and males (HLAB27+ 34%, positive imaging 11%) (all p < 0.01). Moreover, in
      multivariable models with diagnosis of axSpA as outcome, HLA-B27 and imaging
      positivity were associated with the diagnosis in both sexes. In models with
      imaging positivity as outcome, male gender and HLA-B27 were both independently
      associated with MRI+ and/or X-SI+. CONCLUSIONS: While our data show clear gender
      differences in early axSpA, they highlight that HLA-B27 and imaging are still key
      elements for diagnosis in both genders. Our study does not suggest that separate
      diagnostic strategies for men and women are required.

PMID- 30285843
TI  - Draft genome sequence of Staphylococcus sp. EZ-P03 isolated from a mesophilic
      anaerobic digester.
AB  - OBJECTIVES: Staphylococcus species of the family Staphylococcaceae are
      facultatively anaerobic Gram-positive cocci growing in clusters, pairs and
      occasionally in short chains. Staphylococci can be detected in different
      environments. They are common commensals, but some can also cause infections in
      humans. Hence, their investigation is required to understand ecology and genetics
      and to create an opportunity for comparative studies. DATA DESCRIPTION: In this
      study, we report the determination of a draft genome sequence of Staphylococcus
      sp. strain EZ-P03 which was isolated from anaerobically digested chicken waste
      materials. The draft genome of Staphylococcus sp. EZ-P03 constituted a total of
      62 contigs (> 500 bp) amounting to 2,689,358 bp with a G+C content of 37.3% and a
      N50 contig size of 126,562 bp. The whole genome shotgun project of Staphylococcus
      sp. strain EZ-P03 has been deposited at DDBJ/ENA/GenBank under the accession
      number QPMO00000000.

PMID- 30285844
TI  - Activity levels of female Triatoma infestans change depending on physiological
      condition.
AB  - BACKGROUND: Triatoma infestans (Hemiptera: Reduviidae) is the main vector of
      Trypanosoma cruzi, the etiological agent of Chagas disease, in South America.
      Active dispersal of this vector is the principal cause of recolonization of human
      dwellings previously treated with insecticides. Due to the persistence of vector
      populations and their movement between habitats, dispersive behavior studies are
      important for understanding the epidemiology of Chagas disease. The aim of this
      study was to analyze the relationship among T. infestans females' activity levels
      according to their physiological conditions. RESULTS: Two groups of insects were
      used, unfed and fed females. Each was composed of three subgroups in relation to
      the reproductive state: fifth-stage nymphs, virgin and fertilized females. There
      was a significant interaction between reproductive and nutritional states among
      T. infestans female' activity levels. During the experiments, unfed and fed
      nymphs remained inactive. Virgin females showed a dual behavior in their
      movement; fasted insects were more active. Fertilized females, both fed and
      unfed, were always active. CONCLUSION: The reproductive and nutritional
      conditions of T. infestans females affect their activity levels. When females
      with different reproductive states remained together, fertilized females showed
      permanent activity levels, suggesting that this subgroup of females represents
      the highest epidemiological risk as colonizers of human dwellings.

PMID- 30285845
TI  - Is synovial hypertrophy without Doppler activity sensitive to change? Post-hoc
      analysis from a rheumatoid arthritis ultrasound study.
AB  - BACKGROUND: To explore to what extent synovial hypertrophy in joints without
      Doppler activity is a sign of active disease, we investigated the sensitivity to
      change of synovial hypertrophy without Doppler activity during biological disease
      modifying antirheumatic drug (bDMARD) treatment in rheumatoid arthritis (RA)
      patients. METHOD: RA patients initiating or switching bDMARD treatment had
      ultrasound (US) performed on 36 joints at baseline, and at 3 and 6 months.
      Synovial hypertrophy by grayscale US and Doppler activity were graded separately
      from 0 to 3 at the joint level for all time points. Changes in synovial
      hypertrophy in joints without Doppler activity during treatment were assessed and
      compared with changes in synovial hypertrophy in joints with Doppler activity.
      RESULTS: We included 151 patients (82.8% women, 80.1% seropositive for anticyclic
      citrullinated peptide) with a mean +/- standard deviation age of 51.4 +/- 13.2
      years, a disease duration of 9.9 +/- 7.9 years, and baseline Disease Activity
      Score 28-joint count C-reactive peptide (DAS28-CRP) of 4.14 +/- 1.32. At
      baseline, 44.8% of all joints examined (n = 5225) had synovial hypertrophy >= 1
      and 50.7% of these had synovial hypertrophy without Doppler activity. The
      improvement in synovial hypertrophy was similar in joints with and without
      Doppler activity but, when adjusting for the baseline score of synovial
      hypertrophy, joints with synovial hypertrophy without Doppler had a higher
      tendency towards a decrease than joints with synovial hypertrophy with Doppler
      activity independent of grade (3 months: p < 0.0001; 6 months: p = 0.0003).
      CONCLUSION: Joints with synovial hypertrophy without Doppler activity improve
      during treatment, independent of the grade. Thus, SH without Doppler activity is
      not a sign of inactive disease. These findings indicate that joints with synovial
      hypertrophy without Doppler activity should also be taken in to account when
      assessing disease activity by US.

PMID- 30285847
TI  - Comorbidities and the referral pathway to access joint replacement surgery: an
      exploratory qualitative study.
AB  - BACKGROUND: Variation in access to joint replacement surgery has been widely
      reported but less attention has been given to the impact of comorbidities on the
      patient journey to joint replacement surgery. There is a lack of consensus
      amongst healthcare professionals and commissioners about how patients with
      comorbidities should be referred or selected for joint replacement surgery. It is
      therefore important to understand the views of healthcare professionals on the
      management, referral and selection of patients with comorbidities for joint
      replacement surgery. METHODS: An exploratory qualitative study involving semi
      structured interviews with 20 healthcare professionals in England across the
      referral pathway to joint replacement surgery. They were asked to talk about
      their experiences of referring and selecting patients with comorbidities for
      joint replacement surgery. The interviews were audio-recorded and transcribed
      verbatim. Data analysis followed a thematic analysis approach based on the
      principles of grounded theory. RESULTS: In general, the presence of comorbidities
      was not seen as a barrier to being referred or selected for joint replacement but
      was seen as a challenge to manage the patients' journey across the referral
      pathway. Each professional group, concentrated on different aspects of the
      patients' condition which appeared to affect how they managed patients with
      comorbidities. This implied there was a disagreement about roles and
      responsibilities in the management of patients with comorbidities. None of the
      professionals believed it was their responsibility to address comorbidities in
      preparation for surgery. This disagreement was identified as a reason why some
      patients seem to 'get lost' in the referral system when they were considered to
      be unprepared for surgery. Patients were then potentially left to manage their
      own comorbidities before being reconsidered for joint replacement. CONCLUSIONS:
      At the clinician-level, comorbidities were not perceived as a barrier to
      accessing joint replacement surgery but at the pathway-level, it may create an
      implicit barrier such that patients with comorbidities may get 'lost' to the
      system. Further study is needed to explore the roles and responsibilities of
      professionals across the current orthopaedic referral pathway which may be less
      suitable for patients with comorbidities.

PMID- 30285846
TI  - UBN1/2 of HIRA complex is responsible for recognition and deposition of H3.3 at
      cis-regulatory elements of genes in mouse ES cells.
AB  - BACKGROUND: H3.3 is an ancient and conserved H3 variant and plays essential roles
      in transcriptional regulation. HIRA complex, which is composed of HIRA, UBN1 or
      UBN2, and Cabin1, is a H3.3 specific chaperone complex. However, it still remains
      largely uncharacterized how HIRA complex specifically recognizes and deposits
      H3.3 to the chromatin, such as promoters and enhancers. RESULTS: In this study,
      we demonstrate that the UBN1 or UBN2 subunit is mainly responsible for specific
      recognition and direct binding of H3.3 by the HIRA complex. While the HIRA
      subunit can enhance the binding affinity of UBN1 toward H3.3, Cabin1 subunit
      cannot. We also demonstrate that both Ala87 and Gly90 residues of H3.3 are
      required and sufficient for the specific recognition and binding by UBN1. ChIP
      seq studies reveal that two independent HIRA complexes (UBN1-HIRA and UBN2-HIRA)
      can cooperatively deposit H3.3 to cis-regulatory regions, including active
      promoters and active enhancers in mouse embryonic stem (mES) cells. Importantly,
      disruption of histone chaperone activities of UBN1 and UBN2 by FID/AAA mutation
      results in the defect of H3.3 deposition at promoters of developmental genes
      involved in neural differentiation, and subsequently causes the failure of
      activation of these genes during neural differentiation of mES cells. CONCLUSION:
      Together, our results provide novel insights into the mechanism by which the HIRA
      complex specifically recognizes and deposits H3.3 at promoters and enhancers of
      developmental genes, which plays a critical role in neural differentiation of mES
      cells.

PMID- 30285848
TI  - Factor analysis of the Clinical Outcomes in Routine Evaluation - Outcome Measures
      (CORE-OM) in a Kenyan sample.
AB  - BACKGROUND: There is no generic psychotherapy outcome measure validated for
      Kenyan populations. The objective of this study was to test the acceptability and
      factor structure of the Clinical Outcomes in Routine Evaluation - Outcome Measure
      in patients attending psychiatric clinics at two state-owned hospitals in
      Nairobi. METHODS: Three hundred and forty-five patients filled out the CORE-OM
      after their initial therapy session. Confirmatory and Exploratory Factor Analysis
      (CFA/EFA) were used to study the factor structure of the CORE-OM. RESULTS: The
      English version of the CORE-OM seemed acceptable and understandable to
      psychiatric patients seeking treatment at the state-owned hospitals in Nairobi.
      Factor analyses showed that a model with a general distress factor, a risk
      factor, and a method factor for positively framed items fit the data best
      according to both CFA and EFA analysis. Coefficient Omega Hierarchical showed
      that the general distress factor was reliably measured even if differential
      responding to positively framed items was regarded as error variance.
      CONCLUSIONS: The English language version of the CORE-OM can be used with
      psychiatric patients attending psychiatric treatment in Nairobi. The factor
      structure was more or less the same as has been shown in previous studies. The
      most important limitation is the relatively small sample size.

PMID- 30285849
TI  - An expanded global inventory of allelic variation in the most extremely
      polymorphic region of Plasmodium falciparum merozoite surface protein 1 provided
      by short read sequence data.
AB  - BACKGROUND: Within Plasmodium falciparum merozoite surface protein 1 (MSP1), the
      N-terminal block 2 region is a highly polymorphic target of naturally acquired
      antibody responses. The antigenic diversity is determined by complex repeat
      sequences as well as non-repeat sequences, grouping into three major allelic
      types that appear to be maintained within populations by natural selection.
      Within these major types, many distinct allelic sequences have been described in
      different studies, but the extent and significance of the diversity remains
      unresolved. METHODS: To survey the diversity more extensively, block 2 allelic
      sequences in the msp1 gene were characterized in 2400 P. falciparum infection
      isolates with whole genome short read sequence data available from the Pf3K
      project, and compared with the data from previous studies. RESULTS: Mapping the
      short read sequence data in the 2400 isolates to a reference library of msp1
      block 2 allelic sequences yielded 3815 allele scores at the level of major
      allelic family types, with 46% of isolates containing two or more of these major
      types. Overall frequencies were similar to those previously reported in other
      samples with different methods, the K1-like allelic type being most common in
      Africa, MAD20-like most common in Southeast Asia, and RO33-like being the third
      most abundant type in each continent. The rare MR type, formed by recombination
      between MAD20-like and RO33-like alleles, was only seen in Africa and very rarely
      in the Indian subcontinent but not in Southeast Asia. A combination of mapped
      short read assembly approaches enabled 1522 complete msp1 block 2 sequences to be
      determined, among which there were 363 different allele sequences, of which 246
      have not been described previously. In these data, the K1-like msp1 block 2
      alleles are most diverse and encode 225 distinct amino acid sequences, compared
      with 123 different MAD20-like, 9 RO33-like and 6 MR type sequences. Within each
      of the major types, the different allelic sequences show highly skewed
      geographical distributions, with most of the more common sequences being detected
      in either Africa or Asia, but not in both. CONCLUSIONS: Allelic sequences of this
      extremely polymorphic locus have been derived from whole genome short read
      sequence data by mapping to a reference library followed by assembly of mapped
      reads. The catalogue of sequence variation has been greatly expanded, so that
      there are now more than 500 different msp1 block 2 allelic sequences described.
      This provides an extensive reference for molecular epidemiological genotyping and
      sequencing studies, and potentially for design of a multi-allelic vaccine.

PMID- 30285850
TI  - Recruiting care homes to a randomised controlled trial.
AB  - BACKGROUND: There are more than a quarter of a million individuals aged >= 65
      years who are resident in care homes in England and Wales. Care home residents
      have high levels of cognitive impairment, physical disability, multimorbidity and
      polypharmacy. Research is needed to ensure there are robust, evidence-based
      interventions to improve the quality of life of this frail group. However, there
      is a paucity of research studies in this area. Recruiting care homes and their
      residents to research is challenging. A feasibility, cluster randomised
      controlled trial was undertaken as part of a research programme to identify ways
      to develop and test methods to enhance the physical activity of care home
      residents. This paper describes two methods of recruiting care homes to the trial
      and draws out learning to inform future studies. METHODS: Eligible care homes met
      the following criteria: they were within a defined geographical area in the north
      of England; provided residential care for adults >= 65 years of age; had not
      previously been involved in the research programme; were not taking part in a
      conflicting study; were not recorded on the Care Quality Commission website as
      'inadequate' or 'requiring improvements' in any area; and had >= 10 beds. Care
      homes were identified by a 'systematic approach' using the Care Quality
      Commission website database of care homes or a 'targeted approach' via a network
      of research-ready care homes. A standardised method was used to recruit care
      homes including eligibility screening; invitation letters; telephone contact;
      visits; formal letter of agreement. RESULTS: In the systematic approach, 377 care
      homes were screened, 230 (61%) were initially eligible and invited to
      participate, 11 were recruited (recruitment rate (RR) 4.8%). In the targeted
      approach, 15 care homes were invited to participate, two were recruited (RR
      13.3%). Overall, 245 care homes were approached and 13 recruited (RR 5.3%). A
      variety of care homes were recruited to the trial in terms of size, location,
      ownership and care provision. CONCLUSIONS: Systematic recruitment of care homes
      to the study was time-consuming and resource-heavy but led to a variety of care
      homes being recruited. The targeted approach led to a higher recruitment rate.
      TRIAL REGISTRATION: ISRCTN registry, ISRCTN16076575 . Registered on 25 June 2015.

PMID- 30285851
TI  - Hidden in plain sight-highly abundant and diverse planktonic freshwater
      Chloroflexi.
AB  - BACKGROUND: Representatives of the phylum Chloroflexi, though reportedly highly
      abundant in the extensive deep water habitats of both marine (SAR202 up to 30% of
      total prokaryotes) and freshwater (CL500-11 up to 26% of total prokaryotes),
      remain uncultivated and uncharacterized. There are few metagenomic studies on
      marine Chloroflexi representatives, while the pelagic freshwater Chloroflexi
      community is largely unknown except for a single metagenome-assembled genome of
      CL500-11. RESULTS: Here, we provide the first extensive examination of the
      community composition of this cosmopolitan phylum in a range of pelagic habitats
      (176 datasets) and highlight the impact of salinity and depth on their
      phylogenomic composition. Reconstructed genomes (53 in total) provide a
      perspective on the phylogeny, metabolism, and distribution of three novel classes
      and two family-level taxa within the phylum Chloroflexi. We unraveled a
      remarkable genomic diversity of pelagic freshwater Chloroflexi representatives
      that thrive not only in the hypolimnion as previously suspected, but also in the
      epilimnion. Our results suggest that the lake hypolimnion provides a globally
      stable habitat reflected in lower species diversity among hypolimnion-specific
      CL500-11 and TK10 clusters in distantly related lakes compared to a higher
      species diversity of the epilimnion-specific SL56 cluster. Cell volume analyses
      show that the CL500-11 are among the largest prokaryotic cells in the water
      column of deep lakes and with a biomass to abundance ratio of two they
      significantly contribute to the deep lake carbon flow. Metabolic insights
      indicate participation of JG30-KF-CM66 representatives in the global cobalamin
      production via cobinamide to cobalamin salvage pathway. CONCLUSIONS: Extending
      phylogenomic comparisons to brackish and marine habitats suggests salinity as the
      major influencer of the community composition of the deep-dwelling Chloroflexi in
      marine (SAR202) and freshwater (CL500-11) habitats as both counterparts thrive in
      intermediate brackish salinity; however, freshwater habitats harbor the most
      phylogenetically diverse community of pelagic Chloroflexi representatives that
      reside both in epi- and hypolimnion.

PMID- 30285852
TI  - Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients
      with Merkel cell carcinoma and association with response to pembrolizumab.
AB  - BACKGROUND: We recently reported a 56% objective response rate in patients with
      advanced Merkel cell carcinoma (MCC) receiving pembrolizumab. However, a
      biomarker predicting clinical response was not identified. METHODS: Pretreatment
      FFPE tumor specimens (n = 26) were stained for CD8, PD-L1, and PD-1 by
      immunohistochemistry/immunofluorescence (IHC/IF), and the density and
      distribution of positive cells was quantified to determine the associations with
      anti-PD-1 response. Multiplex IF was used to test a separate cohort of MCC
      archival specimens (n = 16), to identify cell types expressing PD-1. RESULTS:
      Tumors from patients who responded to anti-PD-1 showed higher densities of PD-1+
      and PD-L1+ cells when compared to non-responders (median cells/mm2, 70.7 vs. 6.7,
      p = 0.03; and 855.4 vs. 245.0, p = 0.02, respectively). There was no significant
      association of CD8+ cell density with clinical response. Quantification of PD-1+
      cells located within 20 MUm of a PD-L1+ cell showed that PD-1/PD-L1 proximity was
      associated with clinical response (p = 0.03), but CD8/PD-L1 proximity was not.
      CD4+ and CD8+ cells in the TME expressed similar amounts of PD-1. CONCLUSIONS:
      While the binomial presence or absence of PD-L1 expression in the TME was not
      sufficient to predict response to anti-PD-1 in patients with MCC, we show that
      quantitative assessments of PD-1+ and PD-L1+ cell densities as well as the
      geographic interactions between these two cell populations correlate with
      clinical response. Cell types expressing PD-1 in the TME include CD8+ T-cells,
      CD4+ T-cells, Tregs, and CD20+ B-cells, supporting the notion that multiple cell
      types may potentiate tumor regression following PD-1 blockade.

PMID- 30285854
TI  - Racial differences in comorbidity profile among patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often accompanied by
      multiple comorbidities, which are associated with an increased risk of
      exacerbation, a poor health-related quality of life, and high mortality. However,
      differences in comorbidity profile by race and ethnicity in COPD patients have
      not been fully elucidated. METHODS: Participants aged 40 to 79 years with
      spirometry-defined COPD from the U.S. National Health and Nutrition Examination
      Survey (NHANES) (2007-2012) and from the Korea NHANES (2007-2015) were analyzed
      to compare the prevalence of comorbidities by race and ethnicity group.
      Comorbidities were defined using questionnaire data, physical exams, and
      laboratory tests. RESULTS: Non-Hispanic Whites had the highest prevalence of
      dyslipidemia (65.5%), myocardial infarction (6.2%), osteoarthritis (40.1%), and
      osteoporosis (13.6%), while non-Hispanic Blacks had the highest prevalence of
      asthma (24.0%), hypertension (70.2%), stroke (7.3%), diabetes mellitus (DM)
      (23.3%), anemia (16.4%), and rheumatoid arthritis (11.9%). Compared to non
      Hispanic Whites, non-Hispanic Blacks had a significantly higher prevalence of
      hypertension, stroke, DM, anemia, and rheumatoid arthritis after adjusting for
      age, sex, body mass index, and smoking status, while Hispanics had a
      significantly higher prevalence of DM and anemia, and Koreans had significantly
      lower prevalences of all comorbidities except stroke, DM, and anemia.
      CONCLUSIONS: COPD-related comorbidities varied significantly by race and
      ethnicity, and different strategies may be required for the optimal management of
      COPD and its comorbidities in different race and ethnicity groups.

PMID- 30285853
TI  - MiRNA expression profiles in healthy OSAHS and OSAHS with arterial hypertension:
      potential diagnostic and early warning markers.
AB  - BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is prone to being
      complicated with various cardiovascular, cerebrovascular and metabolic
      conditions. OSAHS, due to its multifactorial nature, entails individualized and
      comprehensive treatment. So far, no well-established diagnostic criteria for the
      disease are available. In recent years, miRNA has been shown to be a sensitive
      biomarker suggestive of the progression and prognosis of many diseases. In this
      study, we examined some serum miRNAs in healthy OSAHS (OSAHS patients without
      complication) and OSAHS with arterial hypertension, with an attempt to understand
      the potential effects on the disease, improve the diagnosis of OSAHS and find
      OSAHS-related diagnostic markers. METHODS: Against various diagnostic criteria,
      participants were divided into three groups: healthy OSAHS, OSAHS with arterial
      hypertension and healthy controls. Their serum miRNA profiles were assessed by
      microarray technology, and then differentially expressed miRNAs were verified by
      quantitative real-time PCR (qRT-PCR). The receiver operating characteristic (ROC)
      curves of miRNAs were constructed and the areas under the curve (AUC) were
      calculated. Meanwhile, the miRNAs were subjected to logistic regression analysis.
      The target genes were bioinformatically assessed, their functions and signaling
      pathways further determined and eventually an miRNA-gene network was established.
      RESULTS: Analysis with the miRNA array exhibited that, compared with the control
      group, 12 differentially expressed miRNAs were found in healthy OSAHS, and 33
      were found in OSAHS with arterial hypertension. The expression of miR-126-3p, let
      7d-5p, miR-7641 and miR-1233-5p, miR-320b, miR-145-5p, miR-107, miR-26a-5p were
      validated by using qRT-PCR. Bioinformatics analysis predicted that the potential
      target genes of these miRNAs might be involved in metabolism, and the regulation
      of endothelial cells and nervous system. Moreover, the ROC analysis showed that
      the using miR-145-5p and let-7d-5p in combination can identify the healthy OSAHS,
      presence of miR-126-3p, miR-26a-5p and miR-107 was well indicative of OSAHS with
      arterial hypertension. CONCLUSIONS: A cluster of dysregulation miRNAs have been
      found to be involved in the development of OSAHS patients. Moreover, these miRNAs
      might be used to be potential diagnostic and early warning markers.

PMID- 30285855
TI  - Salmonella Gallinarum delivering M2eCD40L in protein and DNA formats acts as a
      bivalent vaccine against fowl typhoid and H9N2 infection in chickens.
AB  - Fowl typhoid (FT), a septicemic disease caused by Salmonella Gallinarum (SG), and
      H9N2 influenza infection are two economically important diseases that affect
      poultry industry worldwide. Herein, we exploited a live attenuated SG mutant
      (JOL967) to deliver highly conserved extracellular domains of H9N2 M2 (M2e) to
      induce protective immunity against both H9N2 infection and FT. To increase the
      immunogenicity of M2e, we physically linked it with CD40L and cloned the fusion
      gene into either prokaryotic constitutive expression vector pJHL65 or mammalian
      expression vector pcDNA3.1+. Then pJHL65-M2eCD40L or pcDNA-M2eCD40L recombinant
      plasmid was electroporated into JOL967 strain and the resultant clones were
      designated as JOL2074 and JOL2076, respectively. We demonstrated that the
      chickens vaccinated once orally with a co-mix of JOL2074 and JOL2076 strains
      elicited significantly (p < 0.05) higher M2e-specific humoral and cell-mediated
      immunity compared to JOL2074 alone vaccinated group. However, SG-specific immune
      responses were comparable in both the vaccination groups. On challenge with the
      virulent H9N2 virus (105 TCID50) at 28th day post-vaccination, chickens that
      received a co-mix of JOL2074 plus JOL2076 strains exhibited significantly (p <
      0.05) lower lung inflammation and viral load in both lungs and cloacal samples
      than JOL2074 alone vaccinated group. Against challenge with the lethal wild-type
      SG, both the vaccination groups exhibited only 12.5% mortality compared to 75%
      mortality observed in the control group. In conclusion, we show that SG
      delivering M2eCD40L can act as a bivalent vaccine against FT and H9N2 infection
      and further studies are warranted to develop this SG-M2eCD40L vaccine as a
      broadly protective vaccine against avian influenza virus subtypes.

PMID- 30285856
TI  - Durable response to anti-PD-1 immunotherapy in epithelioid angiomyolipoma: a
      report on the successful treatment of a rare malignancy.
AB  - BACKGROUND: Malignant angiomyolipoma is an uncommon tumor of the class of
      perivasciular epithelioid cell neoplasms (PEComas). These tumors are
      characteristically driven by deleterious mutations in the tumor suppressors TSC1
      and TSC2, whose gene products typically act to inhibit mTOR. There are several
      cases of malignant angiomyolipoma which exhibit transient responses to mTOR
      inhibitors, forming the basis of current practice guidelines in malignant PEComa.
      However the tumors ultimately acquire resistance, and there is no well
      established second-line option. Despite the increasing prevalence of
      immunotherapy across a wide range of solid tumors, little is known about the
      immune infiltrate and PD-L1 expression of angiomyolipoma. Furthermore, there is
      no reported case on the treatment of malignant angiomyolipoma with an immune
      checkpoint inhibitor. CASE PRESENTATION: A 38 year-old man presented with gross
      hematuria and was diagnosed with renal epithelioid angiomyolipoma. Despite
      surgical resection, the tumor recurred and metastasized. Targeted genomic
      sequencing revealed a deleterious mutation in TSC2, and the patient was treated
      with the mTOR inihbitor everolimus. The patient went on to have a partial
      response but ultimately progressed. He was then treated with the anti-PD-1 immune
      checkpoint inhibitor nivolumab, and achieved a durable near-complete response
      which is ongoing after two years of treatment. Immunohistochemical staining of
      tumor tissue revealed strong PD-L1 expression and a brisk T-cell infiltrate.
      CONCLUSIONS: We report on the first durable systemic treatment of malignant
      epithelioid angiomyolipoima with the use of PD-1 antibody nivolumab. Given the
      absence of prospective clinical trials in this exceedingly rare disease,
      particularly in the second-line setting, immune checkpoint inhibitors like
      nivolumab should be considered.

PMID- 30285857
TI  - Comparative analysis of rodent and small mammal viromes to better understand the
      wildlife origin of emerging infectious diseases.
AB  - BACKGROUND: Rodents represent around 43% of all mammalian species, are widely
      distributed, and are the natural reservoirs of a diverse group of zoonotic
      viruses, including hantaviruses, Lassa viruses, and tick-borne encephalitis
      viruses. Thus, analyzing the viral diversity harbored by rodents could assist
      efforts to predict and reduce the risk of future emergence of zoonotic viral
      diseases. RESULTS: We used next-generation sequencing metagenomic analysis to
      survey for a range of mammalian viral families in rodents and other small animals
      of the orders Rodentia, Lagomorpha, and Soricomorpha in China. We sampled 3,055
      small animals from 20 provinces and then outlined the spectra of mammalian
      viruses within these individuals and the basic ecological and genetic
      characteristics of novel rodent and shrew viruses among the viral spectra.
      Further analysis revealed that host taxonomy plays a primary role and
      geographical location plays a secondary role in determining viral diversity. Many
      viruses were reported for the first time with distinct evolutionary lineages, and
      viruses related to known human or animal pathogens were identified. Phylogram
      comparison between viruses and hosts indicated that host shifts commonly happened
      in many different species during viral evolutionary history. CONCLUSIONS: These
      results expand our understanding of the viromes of rodents and insectivores in
      China and suggest that there is high diversity of viruses awaiting discovery in
      these species in Asia. These findings, combined with our previous bat virome
      data, greatly increase our knowledge of the viral community in wildlife in a
      densely populated country in an emerging disease hotspot.

PMID- 30285858
TI  - The critical interaction between valproate sodium and warfarin: case report and
      review.
AB  - BACKGROUND: Valproic acid (VPA) and warfarin are commonly prescribed for patients
      with epilepsy and concomitant atrial fibrillation (AF). When VPA and warfarin are
      prescribed together, clinically important interactions may occur. VPA may replace
      warfarin from the protein binding sites and result in an abnormally increased
      anticoagulation effect. This is commonly underrecognized. CASE PRESENTATION: In
      our case, we report a 78-year-old woman with a glioma who presented with status
      epilepticus. The patient was on warfarin to prevent cardiogenic embolism
      secondary to AF. Intravenous loading dose of VPA was administered, but
      international normalized ratio (INR) increased significantly to 8.26. Intravenous
      vitamin K1 was then given and the patient developed no overt bleeding during the
      hospitalization. CONCLUSION: By reviewing the literature and discussing the
      critical interaction between valproate sodium and warfarin, we conclude that
      intravenous VPA and the co-administrated warfarin may develop critical but
      underrecognized complications due to effects on the function of hepatic enzymes
      and displacement of protein binding sites.

PMID- 30285860
TI  - Assessing the role of virtual reality training in Canadian Otolaryngology-Head &
      Neck Residency Programs: a national survey of program directors and residents.
AB  - BACKGROUND: Given mounting pressure of work hour restrictions, resource
      constraints, and variability of clinical exposure, Otolaryngology-Head & Neck
      Surgery (OHNS) residency training has shifted away from the apprenticeship model
      to embrace the Royal College of Physicians and Surgeons of Canada's "Competence
      by Design" initiative. As a result, appraising both current and potential
      educational adjuncts has become increasingly important. In this investigation, a
      national needs assessment survey was performed to identify strengths, weaknesses,
      and future opportunities of the current training landscape. METHODS: An online
      survey was distributed to all thirteen Canadian OHNS post-graduate administrators
      for completion by program directors and residents from February to October in
      2016. Prior to distribution, the survey was vetted for face validity by a group
      of staff Otolaryngologists and questions were modified accordingly. Quantitative
      analysis was performed on SPSS (IBM Corp., Chicago) with non-parametric, two
      tailed Mann-Whitney U testing performed on scaled questions. RESULTS: Of the 68
      responses, 11 of 13 (84.6%) of program directors and 57 of 168 (33.9%) residents
      responded to the survey. All 13 programs currently utilize cadaveric laboratory
      dissections. Associated challenges were ranked as specimen availability, faculty
      participation, insufficient space, and resident time constraints. 30.8% of
      programs currently utilize some form of virtual reality simulator, which 90.9% of
      program directors felt would be a fair and effective platform for evaluation.
      CONCLUSION: A discrepancy exists between the favourable attitudes of both
      residents and program directors towards virtual reality simulation and its actual
      adoption. For successful adoption to occur, the existing barriers to
      unconventional training must be addressed and the tangible benefits for
      competency based training will need to be explored.

PMID- 30285859
TI  - An open-label pilot study on preventing glucocorticoid-induced diabetes mellitus
      with linagliptin.
AB  - BACKGROUND: Numerous patients develop diabetes in response to glucocorticoid
      therapy. This study explored the efficacy, safety, and preventive potential of
      the dipeptidyl peptidase-4 inhibitor, linagliptin (TRADJENTA(r)), in the
      development of glucocorticoid-induced diabetes mellitus. METHODS: From December
      2014 to November 2015, we recruited non-diabetic Japanese patients scheduled for
      treatment with daily prednisolone >=20 mg. Enrolled patients had at least one of
      following risk factors for glucocorticoid-induced diabetes mellitus: estimated
      glomerular filtration rate <= 60 mL/minute/1.73 m2; age >= 65 years; hemoglobin
      A1c > 6.0%. A daily dose of 5 mg of linagliptin was administered simultaneously
      with glucocorticoid therapy. The primary outcome was the development of
      glucocorticoid-induced diabetes mellitus. Additional orally administered
      hypoglycemic medications and/or insulin injection therapy was initiated according
      to the blood glucose level. RESULTS: Four of five patients developed
      glucocorticoid-induced diabetes mellitus within 1 week of glucocorticoid
      treatment. For 12 weeks, two of the four patients with glucocorticoid-induced
      diabetes mellitus required orally administered medications, but no patients
      required insulin. Blood glucose levels before breakfast and lunch tended to
      decrease with time; the median glucose levels before breakfast were 93 and 79.5
      mg/dL at 1 and 3 weeks, respectively. Two patients experienced mild hypoglycemia
      around 2 weeks. Glucose levels after lunch remained high throughout all 4 weeks
      despite decreasing the glucocorticoid dosage. CONCLUSIONS: Linagliptin may be
      insufficient to prevent the development of glucocorticoid-induced diabetes
      mellitus but has the potential to reduce the requirement for insulin injection
      therapy. Treatment of glucocorticoid-induced diabetes mellitus was continued for
      at least 1 month and fasting hypoglycemia in early morning should be monitored
      after 2 weeks. TRIAL REGISTRATION: This trial was registered 02 November 2014
      with UMIN Clinical Trials Registry (no. 000015588 ).

PMID- 30285862
TI  - Assessment of health professional education across five Asian countries-a
      protocol.
AB  - BACKGROUND: There is an increasing consensus globally that the education of
      health professionals is failing to keep pace with scientific, social, and
      economic changes transforming the healthcare environment. This catalyzed a
      movement in reforming education of health professionals across Bangladesh, China,
      India, Thailand, and Vietnam who jointly volunteered to implement and conduct
      cooperative, comparative, and suitable health professional education assessments
      with respect to the nation's socio-economic and cultural status, as well as
      domestic health service system. METHODS: The 5C network undertook a multi-country
      health professional educational study to provide its countries with evidence for
      HRH policymaking. Its scope was limited to the assessment of medical, nursing,
      and public health education at three levels within each country: national,
      institutional, and graduate level (including about to graduate students and
      alumni). RESULTS: This paper describes the general issues related to health
      professional education and the protocols used in a five-country assessment of
      medical, nursing, and public health education. A common protocol for the
      situation analysis survey was developed that included tools to undertake a
      national and institutional assessment, and graduate surveys among about-to
      graduate and graduates for medical, nursing, and public health professions. Data
      collection was conducted through a mixture of literature reviews and qualitative
      research. CONCLUSIONS: The national assessment would serve as a resource for
      countries to plan HRH-related future actions.

PMID- 30285864
TI  - The triennial International Pigment Cell Conference (IPCC).
AB  - The International Federation of Pigment Cell Societies (IFPCS) held its XXIII
      triennial International Pigment Cell Conference (IPCC) in Denver, Colorado in
      August 2017. The goal of the summit was to provide a venue promoting a vibrant
      interchange among leading basic and clinical researchers working on leading-edge
      aspects of melanocyte biology and disease. The philosophy of the meeting,
      entitled Breakthroughs in Pigment Cell and Melanoma Research, was to deliver a
      comprehensive program in an inclusive environment fostering scientific exchange
      and building new academic bridges. This document provides an outlook on the
      history, accomplishments, and sustainability of the pigment cell and melanoma
      research community. Shared progress in the understanding of cellular homeostasis
      of pigment cells but also clinical successes and hurdles in the treatment of
      melanoma and dermatological disorders continue to drive future research
      activities. A sustainable direction of the societies creates an international
      forum identifying key areas of imminent needs in laboratory research and clinical
      care and ensures the future of this vibrant, diverse and unique research
      community at the same time. Important advances showcase wealth and breadth of the
      field in melanocyte and melanoma research and include emerging frontiers in
      melanoma immunotherapy, medical and surgical oncology, dermatology, vitiligo,
      albinism, genomics and systems biology, precision bench-to-bedside approaches,
      epidemiology, pigment biophysics and chemistry, and evolution. This report
      recapitulates highlights of the federate meeting agenda designed to advance
      clinical and basic research frontiers from melanoma and dermatological sciences
      followed by a historical perspective of the associated societies and conferences.

PMID- 30285861
TI  - Host-microbiome interactions and recent progress into understanding the biology
      of acne vulgaris.
AB  - Acne is one of the most common skin diseases worldwide and results in major
      health care costs and significant morbidity to severely affected individuals.
      However, the pathophysiology of this disorder is not well understood. Host
      microbiome interactions that affect both innate and adaptive immune homeostasis
      appear to be a central factor in this disease, with recent observations
      suggesting that the composition and activities of the microbiota in acne is
      perturbed. Staphylococcus epidermidis and Cutibacterium acnes (C. acnes; formerly
      Propionibacterium acnes) are two major inhabitants of the skin that are thought
      to contribute to the disease but are also known to promote health by inhibiting
      the growth and invasion of pathogens. Because C. acnes is ubiquitous in sebaceous
      rich skin, it is typically labeled as the etiological agent of acne yet it fails
      to fulfill all of Koch's postulates. The outdated model of acne progression
      proposes that increased sebum production promotes over-proliferation of C. acnes
      in a plugged hair follicle, thereby driving inflammation. In contrast, growing
      evidence indicates that C. acnes is equally abundant in both unaffected and acne
      affected follicles. Moreover, recent advances in metagenomic sequencing of the
      acne microbiome have revealed a diverse population structure distinct from
      healthy individuals, uncovering new lineage-specific virulence determinants. In
      this article, we review recent developments in the interactions of skin microbes
      with host immunity, discussing the contribution of dysbiosis to the immunobiology
      of acne and newly emerging skin microbiome-based therapeutics to treat acne.

PMID- 30285863
TI  - Projecting the end of the Zika virus epidemic in Latin America: a modelling
      analysis.
AB  - BACKGROUND: Zika virus (ZIKV) emerged in Latin America and the Caribbean (LAC)
      region in 2013, with serious implications for population health in the region. In
      2016, the World Health Organization declared the ZIKV outbreak a Public Health
      Emergency of International Concern following a cluster of associated neurological
      disorders and neonatal malformations. In 2017, Zika cases declined, but future
      incidence in LAC remains uncertain due to gaps in our understanding, considerable
      variation in surveillance and the lack of a comprehensive collation of data from
      affected countries. METHODS: Our analysis combines information on confirmed and
      suspected Zika cases across LAC countries and a spatio-temporal dynamic
      transmission model for ZIKV infection to determine key transmission parameters
      and projected incidence in 90 major cities within 35 countries. Seasonality was
      determined by spatio-temporal estimates of Aedes aegypti vectorial capacity. We
      used country and state-level data from 2015 to mid-2017 to infer key model
      parameters, country-specific disease reporting rates, and the 2018 projected
      incidence. A 10-fold cross-validation approach was used to validate parameter
      estimates to out-of-sample epidemic trajectories. RESULTS: There was limited
      transmission in 2015, but in 2016 and 2017 there was sufficient opportunity for
      wide-spread ZIKV transmission in most cities, resulting in the depletion of
      susceptible individuals. We predict that the highest number of cases in 2018
      would present within some Brazilian States (Sao Paulo and Rio de Janeiro),
      Colombia and French Guiana, but the estimated number of cases were no more than a
      few hundred. Model estimates of the timing of the peak in incidence were
      correlated (p < 0.05) with the reported peak in incidence. The reporting rate
      varied across countries, with lower reporting rates for those with only confirmed
      cases compared to those who reported both confirmed and suspected cases.
      CONCLUSIONS: The findings suggest that the ZIKV epidemic is by and large over
      within LAC, with incidence projected to be low in most cities in 2018. Local low
      levels of transmission are probable, but the estimated rate of infection suggests
      that most cities have a population with high levels of herd immunity.

PMID- 30285866
TI  - The HEART score in predicting major adverse cardiac events in patients presenting
      to the emergency department with possible acute coronary syndrome: protocol for a
      systematic review and meta-analysis.
AB  - BACKGROUND: Acute coronary syndrome (ACS) is a common, sometimes difficult to
      diagnose spectrum of diseases occurring after abrupt reduction in blood flow
      through a coronary artery. Given the diagnostic challenge, it is sensible for
      emergency physicians to have an approach to prognosticate patients with possible
      ACS. Multiple prediction models have been developed to help identify patients at
      increased risk of adverse outcomes. The HEART score is the first model to be
      derived, validated, and undergo clinical impact studies in emergency department
      (ED) patients with possible ACS. OBJECTIVE: To develop a protocol for a
      prognostic systematic review of the literature evaluating the HEART score as a
      predictor of major adverse cardiac events (MACE) in patients presenting to the ED
      with possible ACS. METHODS/DESIGN: This protocol is reported according to the
      PRISMA-P statement and is registered on PROSPERO. All methodological tools to be
      used are endorsed by the Cochrane Prognosis Methods Group. Pre-defined
      eligibility criteria are provided. Multiple strategies will be used to identify
      potentially relevant studies. Studies will be selected and data extracted using
      standardised forms based on the CHARMS checklist. The QUIPS tool will be used to
      assess the risk of bias within individual studies. Outcome measures will include
      prevalence, risk ratio, and absolute risk reduction for MACE within 6 weeks of ED
      evaluation, comparing HEART scores 0-3 versus 4-10. HEART score prognostic
      performance will be evaluated with the concordance (C) statistic (model
      discrimination), observed to expected events ratio (model calibration), and a
      decision curve analysis. Reporting biases and methodological, clinical, and
      statistical heterogeneity will be scrutinised. Unless deemed inappropriate, a
      meta-analysis and pre-defined subgroup and sensitivity analyses will be
      performed. Overall judgements about evidence quality and strength of
      recommendations will be summarised using the GRADE approach. DISCUSSION: This
      review will identify, select, and appraise studies evaluating the prognostic
      performance of the HEART score, producing results of interest to emergency
      physicians. These results may encourage shared clinical decision-making in the ED
      by facilitating risk communication with patients and health care providers.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2017 CRD42017084400 .

PMID- 30285865
TI  - PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple
      myeloma patients and overcome resistance to IMiDs.
AB  - BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disease with a poor
      survival, characterized by the accumulation of myeloma cells (MMCs) within the
      bone marrow. Epigenetic modifications in MM are associated not only with cancer
      development and progression, but also with drug resistance. METHODS: We
      identified a significant upregulation of the polycomb repressive complex 2 (PRC2)
      core genes in MM cells in association with proliferation. We used EPZ-6438, a
      specific small molecule inhibitor of EZH2 methyltransferase activity, to evaluate
      its effects on MM cells phenotype and gene expression prolile. RESULTS: PRC2
      targeting results in growth inhibition due to cell cycle arrest and apoptosis
      together with polycomb, DNA methylation, TP53, and RB1 target genes induction.
      Resistance to EZH2 inhibitor is mediated by DNA methylation of PRC2 target genes.
      We also demonstrate a synergistic effect of EPZ-6438 and lenalidomide, a
      conventional drug used for MM treatment, activating B cell transcription factors
      and tumor suppressor gene expression in concert with MYC repression. We establish
      a gene expression-based EZ score allowing to identify poor prognosis patients
      that could benefit from EZH2 inhibitor treatment. CONCLUSIONS: These data suggest
      that PRC2 targeting in association with IMiDs could have a therapeutic interest
      in MM patients characterized by high EZ score values, reactivating B cell
      transcription factors, and tumor suppressor genes.

PMID- 30285867
TI  - Characteristics of lung cancer among patients with idiopathic pulmonary fibrosis
      and interstitial lung disease - analysis of institutional and population data.
AB  - BACKGROUND: Lung Cancer is occasionally observed in patients with Idiopathic
      Pulmonary Fibrosis (IPF). We sought to describe the epidemiologic and clinical
      characteristics of lung cancer for patients with IPF and other interstitial lung
      disease (ILD) using institutional and statewide data registries. METHODS: We
      conducted a retrospective analysis of IPF and non-IPF ILD patients from the ILD
      center registry, to compare with lung cancer registries at the University of
      Pittsburgh as well as with population data of lung cancer obtained from
      Pennsylvania Department of Health between 2000 and 2015. RESULTS: Among 1108 IPF
      patients, 31 patients were identified with IPF and lung cancer. The age-adjusted
      standard incidence ratio of lung cancer was 3.34 (with IPF) and 2.3 (with non-IPF
      ILD) (between-group Hazard ratio = 1.4, p = 0.3). Lung cancer worsened the
      mortality of IPF (p <  0.001). Lung cancer with IPF had higher mortality compared
      to lung cancer in non-IPF ILD (Hazard ratio = 6.2, p = 0.001). Lung cancer among
      IPF was characterized by a predilection for lower lobes (63% vs. 26% in non-IPF
      lung cancer, p <  0.001) and by squamous cell histology (41% vs. 29%, p = 0.07).
      Increased incidence of lung cancer was observed among single lung transplant
      (SLT) recipients for IPF (13 out of 97, 13.4%), with increased mortality compared
      to SLT for IPF without lung cancer (p = 0.028) during observational period.
      CONCLUSIONS: Lung cancer is approximately 3.34 times more frequently diagnosed in
      IPF patients compared to general population, and associated with worse prognosis
      compared with IPF without lung cancer, with squamous cell carcinoma and lower
      lobe predilection. The causality between non-smoking IPF patients and lung cancer
      is to be determined.

PMID- 30285868
TI  - A nomogram-based immunoprofile predicts overall survival for previously untreated
      patients with esophageal squamous cell carcinoma after esophagectomy.
AB  - BACKGROUND: Immunoscore, as a prognostic tool defined to quantify in situ immune
      cell infiltrates, appears to be superior to the TNM staging system. In esophageal
      squamous cell carcinoma (ESCC), no immunoscore has been established; however, in
      situ tumor immunology is recognized as highly important. Our study aimed to
      construct a comprehensive immunoprofile for ESCC. METHODS: The infiltration of
      four immune cell types (CD8+/CD4+/Foxp3+/CD33+ cells), the expression of both
      inhibitory (PD-1/PD-L1/Tim-3/LAG-3) and stimulatory checkpoints (OX-40/ICOS), and
      IDO1 were evaluated by IHC staining and multi-color immunofluorescence in two
      independent cohorts (95 patients in the primary cohort and 55 patients in the
      validation cohort). The association with patients' overall survival was analyzed
      by the Kaplan-Meier method and the Cox model. Nomogram-based immunoprofile was
      established using the independent prognostic variables. To determine its
      predictive accuracy and discriminatory capacity, the C-index and calibration
      curve were calculated. RESULTS: Significant correlation of PD-L1 expression in
      tumor cells with PD-1+ T cell infiltration was found (P = 0.035), indicating the
      activation of the inhibitory PD-1/PD-L1 pathway in ESCC cases. More PD-L1+ ICs,
      Tim-3+ ICs and LAG-3+ ICs were found in the CD8-rich tumor microenvironment,
      which is in accordance with the feedback nature of immune system. After
      adjustment by TNM stage, four immune variables including the infiltration of
      CD8+/Foxp3+/CD33+ cells and the PD-L1 expression by tumor cells were selected to
      construct a prognostic nomogram. The calibration curves showed good accuracy of
      the nomogram for survival prediction. To overcome the complexity of applying a
      nomogram in a clinical setting, a simple immunoprofile was then established
      according to the points of each factor from the nomogram. Our immunoprofile model
      could separate same-stage patients into different risk subgroups, and showed
      superior accuracy for survival prediction than the TNM staging system based on
      the C-index calculation and ROC analysis. CONCLUSIONS: Our nomogram-based
      immunoprofile can provide more accurate prognosis prediction and is an important
      complement to the TNM staging system for operable ESCC patients.

PMID- 30285870
TI  - Lipolysis and antioxidant properties of cow and buffalo cheddar cheese in
      accelerated ripening.
AB  - BACKGROUND: Buffalo milk is the second largest source of milk on the globe, it is
      highly suitable for the preparation of mozzarella cheese, however, it is not
      suitable for the preparation of cheddar cheese due to high buffering capacity,
      low acid development, excessive syneresis, lower lipolysis that lead to lower
      sensory score. Accelerated ripening can enhance lipolysis and improve sensory
      characteristics of cheddar cheese. Lipolysis and antioxidant capacity of buffalo
      cheddar cheese in conventional ripening is not previously studied. Optimization
      of ripening conditions can lead to better utilization of buffalo milk in cheese
      industry. METHODS: Effect of accelerated ripening on lipolysis and antioxidant
      properties of cow and buffalo cheddar cheese were investigated. Cheddar cheese
      prepared from standardized (3.5% fat) cow and buffalo milk was subjected to
      conventional and accelerated ripening (4  degrees C and 12  degrees C) for a
      period of 120 days. Fatty acid profile, organic acids, free fatty acids,
      cholesterol, antioxidant activity and sensory characteristics were studied at 0,
      40, 80 and 120 days of ripening. RESULTS: Fatty acid profile of cow and buffalo
      cheddar in conventional (120 days old) and accelerated ripening were different
      from each other (p < 0.05). Free fatty acids in 120 days old buffalo and control
      cheddar, in accelerated ripening were 0.55% and 0.62%. After accelerated
      ripening, cholesterol in buffalo and control cheddars were 16 and 72 mg/100 g.
      After accelerated ripening, concentrations of formic, pyruvic, lactic, acetic and
      citric acids in buffalo cheddar cheese were, 922, 136, 19,200, 468 and 2845 ppm.
      At the end of accelerated ripening (120 days), concentrations of formic, pyruvic,
      lactic, acetic and citric acids in cow cheddar cheese were 578, 95, 9600, 347 and
      1015 ppm. Total antioxidant capacity of control cow and buffalo cheddar in
      accelerated ripening was 77.26 and 88.30%. Colour, flavour and texture score of
      rapid ripened 80 and 120 days old buffalo cheddar was not different from cow
      cheddar. CONCLUSIONS: Results of this investigations showed that flavour profile
      buffalo cheddar subjected to accelerate ripening was similar to cow cheddar
      cheese. Accelerated ripening can be used for better utilization of buffalo milk
      in cheddar cheese industry.

PMID- 30285869
TI  - Powered ankle-foot orthoses: the effects of the assistance on healthy and
      impaired users while walking.
AB  - In the last two decades, numerous powered ankle-foot orthoses have been
      developed. Despite similar designs and control strategies being shared by some of
      these devices, their performance in terms of achieving a comparable goal varies.
      It has been shown that the effect of powered ankle-foot orthoses on healthy users
      is altered by some factors of the testing protocol. This paper provides an
      overview of the effect of powered walking on healthy and weakened users. It
      identifies a set of key factors influencing the performance of powered ankle-foot
      orthoses, and it presents the effects of these factors on healthy subjects,
      highlighting the similarities and differences of the results obtained in
      different works. Furthermore, the outcomes of studies performed on elderly and
      impaired subjects walking with powered ankle-foot orthoses are compared, to
      outline the effects of powered walking on these users. This article shows that
      several factors mutually influence the performance of powered ankle-foot orthoses
      on their users and, for this reason, the determination of their effects on the
      user is not straightforward. One of the key factors is the adaptation of users to
      provided assistance. This factor is very important for the assessment of the
      effects of powered ankle-foot orthoses on users, however, it is not always
      reported by studies. Moreover, future works should report, together with the
      results, the list of influencing factors used in the protocol, to facilitate the
      comparison of the obtained results. This article also underlines the need for a
      standardized method to benchmark the actuators of powered ankle-foot orthoses,
      which would ease the comparison of results between the performed studies. In this
      paper, the lack of studies on elderly and impaired subjects is highlighted. The
      insufficiency of these studies makes it difficult to assess the effects of
      powered ankle-foot orthoses on these users.To summarize, this article provides a
      detailed overview of the work performed on powered ankle-foot orthoses,
      presenting and analyzing the results obtained, but also emphasizing topics on
      which more research is still required.

PMID- 30285871
TI  - Identification of two residues within the NS1 of H7N9 influenza A virus that
      critically affect the protein stability and function.
AB  - The emerging avian-origin H7N9 influenza A virus, which causes mild to lethal
      human respiratory disease, continues to circulate in China, posing a great threat
      to public health. Influenza NS1 protein plays a key role in counteracting host
      innate immune responses, allowing the virus to efficiently replicate in the host.
      In this study, we compared NS1 amino acid sequences of H7N9 influenza A virus
      with those of other strains, and determined NS1 protein variability within the
      H7N9 virus and then evaluated the impact of amino acid substitutions on ability
      of the NS1 proteins to inhibit host innate immunity. Interestingly, the amino
      acid residue S212 was identified to have a profound effect on the primary
      function of NS1, since S212P substitution disabled H7N9 NS1 in suppressing the
      host RIG-I-dependent interferon response, as well as the ability to promote the
      virus replication. In addition, we identified another amino acid residue, I178,
      serving as a key site to keep NS1 protein high steady-state levels. When the
      isoleucine was replaced by valine at 178 site (I178V mutation), NS1 of H7N9
      underwent rapid degradation through proteasome pathway. Furthermore, we observed
      that P212S and V178I mutation in NS1 of PR8 virus enhanced virulence and promoted
      the virus replication in vivo. Together, these results indicate that residues
      I178 and S212 within H7N9 NS1 protein are critical for stability and functioning
      of the NS1 protein respectively, and may contribute to the enhanced pathogenicity
      of H7N9 influenza virus.

PMID- 30285872
TI  - Serious adverse events and fatal adverse events associated with nivolumab
      treatment in cancer patients : Nivolumab-related serious/fatal adverse events.
AB  - BACKGROUND: Nivolumab, an immune checkpoint inhibitor, has revolutionized the
      treatment of many cancers. Due to its novel mechanisms of action, nivolumab
      induces a distinct profile of adverse events. Currently, the incidence and risk
      of developing serious adverse events (SAEs) or fatal adverse events (FAEs)
      following nivolumab administration are unclear. METHODS: We conducted a
      systematic search for phase 2 and phase 3 nivolumab trials in PubMed and Embase
      from inception to June 2018. Data on SAEs/FAEs were extracted from each study and
      pooled to calculate the overall incidence and odds ratios (ORs). RESULTS: A total
      of 21 trials with 6173 cancer patients were included in this study. The overall
      incidence of SAEs and FAEs with nivolumab were 11.2% (95% CI, 8.7-13.8%) and 0.3%
      (95% CI, 0.1-0.5%), respectively. The incidence of SAEs varied significantly with
      cancer type and clinical phase, but no evidence of heterogeneity was found for
      FAEs. Compared with conventional treatment, the administration of nivolumab did
      not increase the risk of SAEs (OR, 0.69; 95% CI, 0.34-1.40; p = 0.29) or FAEs
      (OR, 0.61; 95% CI, 0.27-1.39; p = 0.24). SAEs occurred in the major organ systems
      in a dispersed manner, with the most common toxicities appearing in the
      respiratory (21.4%), gastrointestinal (7.7%), and hepatic systems (6.6%). The
      most common cause of SAEs/FAEs was pneumonitis. CONCLUSIONS: Although nivolumab
      is a relatively safe antitumor agent, nononcologists should be advised of the
      potential adverse events. Additionally, future studies are needed to identify
      patients at high risk of SAEs/FAEs to aid in the development of optimal
      monitoring strategies and the exploration of treatments to decrease the risks.

PMID- 30285873
TI  - Vitamin B12 deficiency-induced pseudothrombotic microangiopathy without
      macrocytosis presenting with acute renal failure: a case report.
AB  - BACKGROUND: Vitamin B12 deficiency-induced thrombotic microangiopathy, known as
      pseudothrombotic microangiopathy, is a rare condition which resembles the
      clinical features of thrombotic thrombocytopenic purpura but requires a markedly
      different treatment. Most cases of vitamin B12 deficiency have only mild
      hematological findings, but in approximately 10% of patients life-threatening
      conditions have been reported. CASE PRESENTATION: We report a case of a 46-year
      old Moroccan man presenting with severe hemolytic anemia, thrombocytopenia, and
      renal failure in absence of macrocytosis, thus mimicking a genuine thrombotic
      thrombocytopenic purpura. Rapid improvement of renal function observed with only
      hydration and transfusions of packed red blood cells and the presence of
      pancytopenia suggested a bone marrow deficiency associated to a hemolytic
      component of unclear origin. Detection of low levels of vitamin B12 and rapid
      restitutio ad integrum with its replacement supported the diagnosis of
      pseudothrombotic thrombocytopenic purpura caused by vitamin B12 deficiency.
      CONCLUSIONS: Diagnosis of pseudothrombotic thrombocytopenic purpura caused by
      vitamin B12 deficiency might be difficult. Awareness of clinicians toward this
      differential diagnosis might spare patients from unnecessary therapeutic plasma
      exchange that is burdened by morbidity and mortality.

PMID- 30285874
TI  - Impact of ZBTB7A hypomethylation and expression patterns on treatment response to
      hydroxyurea.
AB  - BACKGROUND: We aimed to clarify the emerging epigenetic landscape in a group of
      genes classified as "modifier genes" of the beta-type globin genes (HBB cluster),
      known to operate in trans to accomplish the two natural developmental switches in
      globin expression, from embryonic to fetal during the first trimester of
      conception and from fetal to adult around the time of birth. The epigenetic
      alterations were determined in adult sickle cell anemia (SCA) homozygotes and
      SCA/beta-thalassemia compound heterozygotes of Greek origin, who are under
      hydroxyurea (HU) treatment. Patients were distinguished in HU responders and HU
      non-responders (those not benefited from the HU) and both, and in vivo and in
      vitro approaches were implemented. RESULTS: We examined the CpG islands' DNA
      methylation profile of BCL11A, KLF1, MYB, MAP3K5, SIN3A, ZBTB7A, and GATA2, along
      with gamma-globin and LRF/ZBTB7A expression levels. In vitro treatment of
      hematopoietic stem cells (HSCs) with HU induced a significant DNA hypomethylation
      pattern in ZBTB7A (p*, 0.04) and GATA2 (p*, 0.03) CpGs exclusively in the HU non
      responders. Also, this group of patients exhibited significantly elevated
      baseline methylation patterns in ZBTB7A, before the HU treatment, compared to HU
      responders (p*, 0.019) and to control group of healthy individuals (p*, 0.021),
      which resembles a potential epigenetic barrier for the gamma-globin expression.
      gamma-Globin expression in vitro matched with detected HbF levels during
      patients' monitoring tests (in vivo) under HU treatment, implying a good
      reproducibility of the in vitro HU epigenetic effect. LRF/ZBTB7A expression was
      elevated only in the HU non-responders under the influence of HU. CONCLUSIONS:
      This is one of the very first pharmacoepigenomic studies indicating that the
      hypomethylation of ZBTB7A during HU treatment enhances the LRF expression, which
      by its turn suppresses the HbF resumption in the HU non-responders. Its role as
      an epigenetic regulator of hemoglobin switching is also supported by the wide
      distribution of ZBTB7A-binding sites within the 5' CpG sequences of all studied
      human HBB cluster "modifier genes." Also, the baseline methylation level of
      selective CpGs in ZBTB7A and GATA2 could be an indicator of the negative HU
      response among the beta-type hemoglobinopathy patients.

PMID- 30285875
TI  - Improving preventive and health promotion care for children.
AB  - The emerging science in early childhood development challenges past paradigms of
      health care. There is consideration within the profession of paediatrics, and
      health care more broadly, of how to make systems of care more responsive to the
      developmental and social needs of young children and their families. Some
      countries have physician-centric models, either general physicians or
      paediatricians, while others rely on nurses. There is increasing recognition that
      the goal of any model should be parent-professional partnership that puts
      families at the center, elicits and responds to family needs, anticipates and
      supports families with developmental transitions, and fits within a seamless
      system of services and supports.

PMID- 30285876
TI  - Survival of patients with chronic heart failure in the community: a systematic
      review and meta-analysis protocol.
AB  - BACKGROUND: Heart failure (HF) is a common condition affecting more than 10% of
      those over 70 years of age. Reliable estimates of survival following a diagnosis
      of HF are important to guide management and facilitate advanced care planning.
      Most existing research has focused on survival rates for patients admitted to
      hospital with acute HF. However, the majority of patients with HF are diagnosed
      in the outpatient setting and can have periods of sustained symptom stability in
      the chronic phase of their illness. There has not been a systematic review of the
      literature to determine the prognosis of patients with chronic HF in the
      community. METHODS: We will undertake a comprehensive search of the following
      databases: CINAHL, Database of Abstracts of Reviews of Effects, Embase, MEDLINE
      and the Clinical Trials Register ( clinicaltrials.gov ). Two reviewers will
      independently complete screening, data extraction and quality appraisal with the
      option of input from a third reviewer to arbitrate. We will include data from
      observational or database studies conducted in either community or outpatient
      settings. Studies of acute HF or specific subgroups of patients will be excluded.
      There is no restriction by geographical setting, publication language or study
      date. We will complete QUIPS and GRADE assessments to systematically appraise the
      quality of evidence within and between studies. Where possible, we will seek to
      pool results to conduct a meta-analysis and undertake relevant subgroup analysis
      including by study setting, participant age and study decade. The primary outcome
      will be survival time from diagnosis. The secondary outcomes will be HF-related
      hospital admissions, symptom burden and measures of morbidity. DISCUSSION: This
      systematic review will provide up to date evidence on the current survival rates
      and prognostic indicators for patients with chronic HF. We will put this into
      historical perspective, comparing outcomes across time to help understand the
      impact of advances in evidence-based treatment on average survival. This
      information is important in facilitating informed decision-making for patients
      and health professionals as well as highlighting areas to focus resources and
      improve public health planning. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2017
      CRD42017075680.

PMID- 30285877
TI  - Does taking statins affect the pathological burden in autopsy-confirmed
      Alzheimer's dementia?
AB  - BACKGROUND: The efficacy of cholesterol lowering agents, specifically statins, in
      slowing the rate of decline of cognitive function in Alzheimer's disease (AD)
      patients is not yet fully understood. Our team's previously published paper
      showed that patients who used statins demonstrated no increase in cognitive
      decline in mild cognitive impairment when compared with nonusers. Further, AD
      patients on statins demonstrated a slight decreasing trend in cognitive decline.
      The purpose of this study is therefore to investigate the association between
      stain use in AD confirmed by clinical diagnosis and autopsy and the pathological
      burden (plaques, tangles, Braak stage). The hypothesis leading this investigation
      is that prolonged statin use associates with lower AD pathology at autopsy.
      METHODS: We queried the National Alzheimer's Coordinating Center (NACC) database
      for autopsy-confirmed AD cases. Of the Uniform Data Set (UDS) participants who
      are deceased, 16,163 were diagnosed with dementia at their last UDS visit prior
      to death, and autopsy data are available for 3945 patients. These patients were
      then stratified into two groups based upon statin use. The two groups were then
      analyzed for their pathological AD burden, including total plaques, total
      tangles, age at death, age of onset, and Braak stage. RESULTS: NACC data were
      available for 1816 subjects with clinically and pathologically confirmed AD; 1558
      were not on statins and 258 were on statins. No significant differences in age at
      death, age at onset, Braak stages, mean total tau, and mean total amyloid were
      found between the two subject groups. When statin use was analyzed by
      apolipoprotein E (ApoE) genotype carrier statins, the presence of ApoE4 did not
      influence the effects (or lack thereof) of statin use. CONCLUSIONS: Prolonged
      statin use in pathologically confirmed AD dementia does not appear to influence
      the amount of burden of plaques and tangles or Braak stage. These observations
      were not altered by the presence of absence of ApoE4.

PMID- 30285878
TI  - Circular RNA BCRC-3 suppresses bladder cancer proliferation through miR-182
      5p/p27 axis.
AB  - BACKGROUND: Circular RNAs (circRNAs) are a new member of noncoding RNAs (ncRNAs)
      that have recently been described as key regulators of gene expression. Our
      previous study had identified the negative correlation between circHIPK3 and
      bladder cancer grade, invasion, as well as lymph node metastasis. However, the
      roles of circRNAs in cellular proliferation in bladder cancer remain largely
      unknown. METHODS: We had analyzed circRNA high-throughout sequencing from human
      tissues and determined bladder cancer related circRNA-3 (BCRC-3, GenBank:
      KU921434.1) as a new candidate circRNA derived from PSMD1 gene. The expression
      levels of circRNAs, mRNAs and miRNAs in human tissues and cells were detected by
      quantitative real-time PCR (qRT-PCR). The effects of BCRC-3 on cancer cells were
      explored by transfecting with plasmids in vitro and in vivo. RNA pull down assay,
      luciferase reporter assay and fluorescence in situ hybridization were applied to
      verify the interaction between BCRC-3 and microRNAs. Anticancer effects of methyl
      jasmonate (MJ) were measured by flow cytometry assay, western blot and qRT-PCR.
      RESULTS: BCRC-3 was lowly expressed in bladder cancer tissues and cell lines.
      Proliferation of BC cells was suppressed by ectopic expression of BCRC-3 in vitro
      and in vivo. Mechanistically, overexpression of BCRC-3 induced the expression of
      cyclin-dependent kinase inhibitor 1B (p27). Importantly, BCRC-3 could directly
      interact with miR-182-5p, and subsequently act as a miRNA sponge to promote the
      miR-182-5p-targeted 3'UTR activity of p27. Furthermore, MJ significantly
      increased the expression of BCRC-3, resulting in an obvious up-regulation of p27.
      CONCLUSIONS: BCRC-3 functions as a tumor inhibitor to suppress BC cell
      proliferation through miR-182-5p/p27 axis, which would be a novel target for BC
      therapy.

PMID- 30285880
TI  - Prognostic value of microRNAs in head and neck cancers: a systematic review and
      meta-analysis protocol.
AB  - BACKGROUND: Head and neck cancers form a significant share of all cancer
      incidences worldwide. Though treatment modalities exist, post-treatment
      recurrence and survival rates in recurrent patients continue to be high. MiRNAs
      offer an effective method of estimating the probability of recurrence and
      survival of HNC patients, thereby allowing for effective treatment and better
      survival rates. METHODS: The systematic review protocol was prepared according to
      the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols
      (PRISMA-P) 2015 statement. Relevant studies will be identified by a rigorous
      search of multiple bibliographical databases, including MEDLINE, Scopus, PubMed,
      Web of Science, Embase and Science Direct, without any language restrictions (up
      to June 2018). The primary screening will be performed by a review team via
      analysis of titles and abstracts of published articles. Final selection of
      articles will be achieved by two independent reviewers, based on predefined
      selection criteria. Data will be extracted from eligible studies using a pre
      piloted data extraction form. Statistical analysis will be performed on the basis
      of available data, extracted from eligible studies. Meta-analysis will be
      performed, and a forest plot will be generated, to determine pooled hazard ratios
      (HR) and 95% confidence interval (CI) using CMA. A fixed or random-effects model
      of meta-analysis will be used depending upon the between-study heterogeneity;
      publication bias will be determined by the Egger's bias indicator test. A
      narrative synthesis will be undertaken where statistical data is found to be
      insufficient. DISCUSSION: There is a lack of highly sensitive and specific
      biomarkers for estimating the HNC patients' prognostic outcomes, particularly in
      post-treatment conditions. This systematic review will identify and validate
      specific miRNA as prognostic biomarkers by utilising a collection of previously
      published data on miRNA expression and survival. Highlighting these prognostic
      specific miRNAs will have major clinical implications by allowing for better
      overall treatment strategies and patient survival estimates, by offering
      clinicians a method of quantitatively analysing prognosis via miRNA expression.
      SYSTEMATIC REVIEW REGISTRATION: This review protocol was registered on PROSPERO
      and assigned the registration number CRD42017077411 .

PMID- 30285879
TI  - Robotic renal cyst decortication with calyceal diverticulectomy in a toddler -
      technical practicalities: a case report.
AB  - BACKGROUND: Incidence of simultaneous renal cyst with calyceal diverticula in
      contralateral kidney is rare in children. A minimally invasive procedure in
      different sittings is often recommended. CASE PRESENTATION: A Chinese 15-month
      old boy presented to the Urology department of a tertiary care center with right
      flank pain. He was subjected to magnetic resonance urography and was diagnosed as
      having right renal cyst and contralateral calyceal diverticula. He underwent
      robotic cyst decortication and calyceal diverticulectomy using da Vinci robot.
      His postoperative period was uneventful. He was discharged on fifth postoperative
      day. Histopathology was consistent with simple renal cyst. CONCLUSIONS: Robotic
      combined cyst decortication and contralateral diverticulectomy is feasible in
      selected small children. However, it demands adequate technical skill and
      experience.

PMID- 30285881
TI  - Surgical peritoneal stress creates a pro-metastatic niche promoting resistance to
      apoptosis via IL-8.
AB  - BACKGROUND: The mainstay of treatment of advanced ovarian cancer (AOC) involves
      chemotherapy, and debulking surgery. However, despite optimal surgical procedure
      and adjuvant chemotherapy, 60% of patients with AOC will relapse within 5 years.
      Most recurrences occur in the peritoneal cavity, suggesting the existence of
      occult sanctuaries where ovarian cancer cells (OCC) are protected. In murine
      models, surgical stress favors tumor growth; however, it has never been
      established that surgery may affect OCC sensitivity to subsequent chemotherapy.
      In this study, we investigated how the surgical stress could affect the
      chemosensitivity of OCC. METHODS: To avoid bias due to tumor burden in peritoneal
      cavity and duration of surgery, we used peritoneal biopsies from patients without
      a malignancy at precise time points. During laparotomies, peritoneal biopsies at
      the incision site were performed at the time of incision (H0 sample) and 1 h
      after initiation of surgery (H1 sample). We evaluated the chemoresistance to
      Taxol (0-20 uM) induced by H0 or H1 incubation (24 h) in two ovarian cancer cell
      lines OVCAR3 and SKOV3 and a primary cancer cell lines derived in our laboratory.
      RESULTS: Our results indicate that stressed peritoneum overexpressed cytokines,
      resulting in OCC increased resistance to therapy. Among these cytokines, IL8 was
      responsible for the resistance to apoptosis through the AKT pathway activation.
      Chemoresistance in OCC persists through the establishment of an autocrine IL8
      loop. Finally, in a cohort of 32 patients, we showed an impact of IL8 tumoral
      overexpression on chemosensitivity and survival outcomes with a significant
      association to earlier recurrence. CONCLUSIONS: Our study demonstrated that
      precision surgery where targeted treatment would be used in combination with
      surgery is essential to obtain better tumor control.

PMID- 30285882
TI  - Concentrations of nicotine, nitrosamines, and humectants in legal and illegal
      cigarettes in Mexico.
AB  - BACKGROUND: Article 10 of the World Health Organization Framework Convention on
      Tobacco Control states the need for industry disclosure of tobacco contents and
      emissions. Currently, the profiles of key tobacco compounds in legal and illegal
      cigarettes are largely unknown. We aimed to analyze and compare concentrations of
      nicotine, nitrosamines, and humectants in legal and illegal cigarettes collected
      from a representative sample of smokers. METHODS: Participants of the
      International Tobacco Control cohort provided a cigarette pack of the brand they
      smoked during the 2014 wave. Brands were classified as legal or illegal according
      to the Mexican legislation. Nicotine, nitrosamines, glycerol, propylene glycol,
      and pH were quantified in seven randomly selected packs of each brand. All
      analyses were done blinded to legality status. Average concentrations per brand
      and global averages for legal and illegal brands were calculated. Comparisons
      between legal and illegal brands were conducted using t tests. RESULTS:
      Participants provided 76 different brands, from which 6.8% were illegal. Legal
      brands had higher nicotine (15.05 +/- 1.89 mg/g vs 12.09 +/- 2.69 mg/g; p <
      0001), glycerol (12.98 +/- 8.03 vs 2.93 +/- 1.96 mg/g; p < 0.001), and N
      nitrosanatabine (NAT) (1087.5 +/- 127.0 vs 738.5 +/- 338 ng/g; p = 0.006)
      concentrations compared to illegal brands. For all other compounds, legal and
      illegal brands had similar concentrations. CONCLUSION: Compared to illegal
      cigarettes, legal brands seem to have higher concentrations of nicotine, NAT, and
      glycerol. Efforts must be made to implement and enforce Article 10 of the
      Framework Convention on Tobacco Control to provide transparent information to
      consumers, regulators, and policy-makers; and to limit cigarette engineering from
      the tobacco industry.

PMID- 30285883
TI  - Breast cancer survival predicted by TP53 mutation status differs markedly
      depending on treatment.
AB  - BACKGROUND: Previous studies on the role of TP53 mutation in breast cancer
      treatment response and survival are contradictory and inconclusive, limited by
      the use of different endpoints to determine clinical significance and by small
      sample sizes that prohibit stratification by treatment. METHODS: We utilized
      large datasets to examine overall survival according to TP53 mutation status in
      patients across multiple clinical features and treatments. RESULTS: Confirming
      other studies, we found that in all patients and in hormone therapy-treated
      patients, TP53 wild-type status conferred superior 5-year overall survival, but
      survival curves crossed at 10 or more years. In contrast, further stratification
      within the large dataset revealed that in patients receiving chemotherapy and no
      hormone therapy, wild-type TP53 status conferred remarkably poor overall
      survival. This previously unrecognized inferior survival is consistent with p53
      inducing arrest/senescence instead of apoptosis. Addition of hormone therapy to
      chemotherapy improved survival notably in patients with TP53 wild-type tumors,
      but not mutant, suggesting hormone therapy could eradicate arrested/senescent
      cells. Testing this, we found that estrogen receptor-positive, TP53 wild-type
      breast cancer cells that were made senescent by doxorubicin treatment were
      sensitive to tamoxifen. CONCLUSIONS: The poor survival of chemotherapy-treated
      patients with TP53 wild-type tumors may be improved by strategies to eliminate
      senescent cells, including the addition of hormone therapy when appropriate.

PMID- 30285884
TI  - A retrospective dosimetry study of intensity-modulated radiotherapy for
      nasopharyngeal carcinoma: radiation-induced brainstem injury and dose-volume
      analysis.
AB  - BACKGROUND: Radiation therapy is the standard radical treatment for
      nasopharyngeal carcinoma (NPC) but also causes transient as well as long-term
      complications. Patients who develop severe radiation-induced brainstem injuries
      have a poor prognosis due to the lack of effective medical therapies. However,
      the relationship between brainstem injury and radiation volume dose is unknown.
      In this study, we found that radiation-induced brainstem injury was significantly
      associated with brainstem dose per unit volume. METHODS: A retrospective analysis
      was performed on a consecutive cohort of 327 patients with NPC receiving IMRT
      from May 2005 to December 2014. Dose-volume data and long-term outcome were
      analyzed. RESULTS: The median follow-up duration was 56 months (range, 3-141
      months), and six with T4 and two with T3 patients had radiation-induced brainstem
      injuries. The 3-year and 5-year incidences were 2.2% and 2.8%, respectively. The
      latency period of brainstem injury ranged from 9 to 58 months, with a median
      period of 21 months. The Cox regression analysis showed that brainstem radiation
      toxicity was associated with the T4 stage, D2% of gross tumor volume of
      nasopharyngeal primary lesions and their direct extensions (GTVnx), Dmax (the
      maximum point dose), D1%, D0.1cc (the top dose delivered to a 0.1-ml volume), and
      D1cc (the top dose delivered to a 1-ml volume) of the brainstem (p < 0.05).
      Receiver operating characteristic (ROC) curves showed that GTVnx D2% and the
      Dmax, D1%, D0.1cc, and D1cc of the brainstem were significant predictors of
      brainstem injury. The area under the ROC curve for these five parameters was
      0.724, 0.813, 0.818, 0.818, and 0.798, respectively (p < 0.001), and the cutoff
      points 77.26 Gy, 67.85 Gy, 60.13 Gy, 60.75 Gy, and 54.58 Gy, respectively, were
      deemed as the radiation dose limit. CONCLUSIONS: Radiotherapy-induced brainstem
      injury was uncommon in patients with NPC who received definitive IMRT. Multiple
      dose-volume data may be the dose tolerance of radiation-induced brainstem injury.

PMID- 30285885
TI  - MiR-425 expression profiling in acute myeloid leukemia might guide the treatment
      choice between allogeneic transplantation and chemotherapy.
AB  - BACKGROUND: Acute myeloid leukemia (AML) is a highly heterogeneous disease.
      MicroRNAs function as important biomarkers in the clinical prognosis of AML.
      METHODS: This study identified miR-425 as a prognostic factor in AML by screening
      the TCGA dataset. A total of 162 patients with AML were enrolled for the study
      and divided into chemotherapy and allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) groups. RESULTS: In the chemotherapy group, patients
      with high miR-425 expression had significantly longer overall survival (OS) and
      event-free survival (EFS) compared with patients with low miR-425 expression. In
      multivariate analyses, high miR-425 expression remained independently predictive
      of a better OS (HR = 0.502, P = 0.005) and EFS (HR = 0.432, P = 0.001) compared
      with patients with low miR-425 expression. Then, all patients were divided into
      two groups based on the median expression levels of miR-425. Notably, the
      patients undergoing allo-HSCT had significantly better OS (HR = 0.302, P <
      0.0001) and EFS (HR = 0.379, P < 0.0001) compared with patients treated with
      chemotherapy in the low-miR-425-expression group. Mechanistically, high miR-425
      expression levels were associated with a profile significantly involved in
      regulating cellular metabolism. Among these genes, MAP3K5, SMAD2, and SMAD5 were
      predicted targets of miR-425. CONCLUSIONS: The expression of miR-425 may be
      useful in identifying patients in need of strategies to select the optimal
      therapy between chemotherapy and allo-HSCT treatment regimens. Patients with low
      miR-425 expression may consider early allo-HSCT.

PMID- 30285886
TI  - Primary pulmonary meningioma mimicking lung metastatic tumor: a case report.
AB  - BACKGROUND: Primary pulmonary meningioma (PPM) is an extremely rare benign tumor.
      Previous reports indicated that CT features of PPM are single, solid, well
      demarcated, homogeneous mass. In this study, we report a case of PPM with
      atypical CT features. CASE PRESENTATION: A 65-year-old female presents to clinic
      with 1-week acute upper respiratory tract infection. Her chest CT scan revealed a
      25-29 mm, round-like, heterogeneous lobulated solitary pulmonary nodule in the
      right lower lobe. Based on the microscopic features and a wide range of
      immunohistochemical examinations including vimentine, progesterone receptor (PR),
      CD34 and S100, the mass was diagnosed as PPM after surgery. CONCLUSION: PPM is a
      rare disease, CT features of PPM could be heterogeneous and lobulated. Expression
      of vimentine, PR, CD34 and S100 helps to diagnosis of PPM.

PMID- 30285887
TI  - Assessment of left ventricular systolic and diastolic abnormalities in patients
      with hypertrophic cardiomyopathy using real-time three-dimensional
      echocardiography and two-dimensional speckle tracking imaging.
AB  - BACKGROUND: Conventional echocardiography is not sensitive enough to assess left
      ventricular (LV) dysfunction in hypertrophic cardiomyopathy (HCM) patients. This
      research attempts to find a new ultrasonic technology to better assess LV
      diastolic function, systolic function, and myocardial longitudinal and
      circumferential systolic strain of segments with different thicknesses in HCM
      patients. METHODS: This study included 50 patients with HCM and 40 healthy
      subjects as controls. The peak early and late mitral annulus diastolic velocities
      at six loci (Ea' and Aa', respectively) and the Ea'/Aa' ratio were measured using
      real-time tri-plane echocardiography and quantitative tissue velocity imaging (RT
      3PE-QTVI). The mean value of Ea' at six loci (Em') was obtained for the
      calculation of E/Em' ratio. The LV end-diastolic volume (LVEDV), LV end-systolic
      volume (LVESV), LV stroke volume (LVSV), and LV ejection fraction (LVEF) were
      measured using real-time three-dimensional echocardiography (RT-3DE). LV
      myocardial longitudinal peak systolic strain (LPSS) and circumferential peak
      systolic strain (CPSS) in the apical-middle-basal segments (LPSS-api, LPSS-mid,
      LPSS-bas; CPSS-api, CPSS-mid, and CPSS-bas, respectively) were obtained using a
      software for two-dimensional speckle tracking imaging (2D-STI). According to the
      different segmental thicknesses (STs) in each HCM patient, the values (LPSS and
      CPSS) of all the myocardial segments were categorized into three groups and the
      respective averages were computed. RESULTS: The Ea', Aa', and, Ea'/Aa' ratio in
      HCM patients were lower than those in the controls (all p < 0.001), while the
      E/Em' ratio in HCM patients was higher than that in the controls (p < 0.001). The
      LVEDV, LVSV, and LVEF were significantly lower in HCM patients than in controls
      (all p < 0.001). In HCM patients, the LPSS-api, LPSS-mid, LPSS-bas, CPSS-api,
      CPSS-mid, and CPSS-bas and the LPSS and CPSS of LV segments with different
      thicknesses were all significantly reduced (all p < 0.001). CONCLUSIONS: In HCM
      patients, myocardial dysfunction was widespread not only in the obviously
      hypertrophic segments but also in the non-hypertrophic segments; the LV systolic
      and diastolic functions were damaged, even with a normal LVEF. LV diastolic
      dysfunction, systolic dysfunction, and myocardial deformation impairment in HCM
      patients can be sensitively revealed by RT-3PE-QTVI, RT-3DE, and 2D-STI.

PMID- 30285888
TI  - Using concept mapping to develop a human rights based indicator framework to
      assess country efforts to strengthen rehabilitation provision and policy: the
      Rehabilitation System Diagnosis and Dialogue framework (RESYST).
AB  - BACKGROUND: Rehabilitation is crucial for the realization of the right to health
      and a proper concern of global health. Yet, reliable information to guide
      rehabilitation service planning is unavailable in many countries in part due to
      the lack of appropriate indicators. To ensure universal health coverage and meet
      the central imperative of "leaving no one behind" countries must be able to
      assess key aspects of rehabilitation policy and provision and monitor how they
      have discharged their human rights responsibilities towards those most
      disadvantaged, including people with disability. This article describes the
      process of developing an expert guided indicator framework to assess governments'
      efforts and progress in strengthening rehabilitation in line with the Convention
      on the Rights of Persons with Disabilities. METHODS: A systems methodology -
      concept mapping - was used to capture, aggregate and confirm the knowledge of
      diverse stakeholders on measures thought to be useful for monitoring the
      implementation of the Convention with respect to health related rehabilitation.
      Fifty-six individuals generated a list of 107 indicators through online
      brainstorming which were subsequently sorted by 37 experts from the original
      panel into non overlapping categories. Forty-one participants rated the
      indicators for importance and feasibility. Multivariate statistical techniques
      where used to explore patterns and themes in the data and create the indicators'
      organizing framework which was verified and interpreted by a select number of
      participants. RESULTS: A concept map of 11 clusters of indicators emerged from
      the analysis grouped into three broader themes: Governance and Leadership (3
      clusters); Service Delivery, Financing and Oversight (6 clusters); and Human
      Resources (2 clusters). The indicator framework was comprehensive and well
      aligned with the Convention. On average, there was a moderately positive
      correlation between importance and feasibility of the indicators (r = .58) with
      experts prioritizing the indicators contained in the clusters of the Governance
      and Leadership domain. Two of the most important indicators arose from the
      Service Delivery, Financing and Oversight domain and reflect the need to monitor
      unmet needs and barriers in access to rehabilitation. In total, 59 indicators
      achieved above average score for importance and comprised the two-tiered priority
      set of indicators. CONCLUSION: Concept mapping was successful in generating a
      shared model that enables a system's view of the most critical legal, policy and
      programmatic factors that must be addressed when assessing country efforts to
      reform, upscale and improve rehabilitation services. The Rehabilitation Systems
      Diagnosis and Dialogue framework provides a data driven basis for the development
      of standardized data collection tools to facilitate comparative analysis of
      rehabilitation systems. Despite agreement on the importance and feasibility of 59
      indicators, further research is needed to appraise the applicability and utility
      of the indicators and secure a realistic assessment of rehabilitation systems.

PMID- 30285889
TI  - Novel 4D-MRI of tumor infiltrating vasculature: characterizing tumor and vessel
      volume motion for selective boost volume definition in pancreatic radiotherapy.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma has dismal prognosis. Most patients
      receive radiation therapy (RT), which is complicated by respiration induced organ
      motion in upper abdomen. The purpose of this study is to report our early
      clinical experience in a novel self-gated k-space sorted four-dimensional
      magnetic resonance imaging (4D-MRI) with slab-selective (SS) excitation to
      highlight tumor infiltrating blood vessels for pancreatic RT. METHODS: Ten
      consecutive patients with borderline resectable or locally advanced pancreatic
      cancer were recruited to the study. Non-contrast 4D-MRI with and without slab
      selective excitation and 4D-CT with delay contrast were performed on all
      patients. Vessel-tissue CNR were calculated for aorta and critical vessels
      (superior mesenteric artery or superior mesenteric vein) encompassed by tumor.
      Respiratory motion trajectories for tumor, as well as involved vessels were
      analyzed on SS-4D-MRI. Intra-class cross correlation (ICC) between tumor volume
      and involved vessels were calculated. RESULTS: Among all 4D imaging modalities
      evaluated, SS-4D-MRI sampling trajectory results in images with highest vessel
      tissue CNR comparing to non-slab-selective 4D-MRI and 4D-CT for all patients
      studied. Average (+/-standard deviation) CNR for involved vessels are 13.1 +/-
      8.4 and 3.2 +/- 2.7 for SS-4D-MRI and 4D-CT, respectively. The ICC factors
      comparing tumor and involved vessels motion trajectories are 0.93 +/- 0.10, 0.65
      +/- 0.31 and 0.77 +/- 0.23 for superior-inferior, anterior-posterior and medial
      lateral directions respectively. CONCLUSIONS: A novel 4D-MRI sequence based on 3D
      radial sampling and slab-selective excitation has been assessed for pancreatic
      cancer patients. The non-contrast 4D-MRI images showed significantly better
      contrast to noise ratio for the vessels that limit tumor resectability compared
      to 4D-CT with delayed contrast. The sequence has great potential in accurately
      defining both the tumor and boost volume margins for pancreas RT with
      simultaneous integrated boost.

PMID- 30285890
TI  - Attenuated bidirectional short-term synaptic plasticity in the dentate gyrus of
      Schnurri-2 knockout mice, a model of schizophrenia.
AB  - The dentate gyrus of the hippocampus has been implicated in the
      pathophysiological basis of neuropsychiatric disorders including schizophrenia.
      We have identified several mouse models of neuropsychiatric disorders with robust
      molecular and functional defects in the dentate gyrus. Among them, mice lacking
      Schnurri-2 (Shn2 or HIVEP2) have been proposed as a model of schizophrenia and
      intellectual disability. Shn2 knockout mice exhibit behavioral abnormalities
      resembling symptoms of schizophrenia and HIVEP2-related intellectual disability
      as well as marked functional alterations in the soma and output synapse of the
      dentate granule cells (GCs). Although robust abnormalities were also observed in
      the dendritic spine morphology in the GCs, their functional correlates remain
      unknown. In the present study, we performed electrophysiological analyses of
      synaptic transmission at the medial perforant path (MPP) input onto the GCs in
      Shn2 knockout mice. While the basal synaptic efficacy was preserved, short-term
      synaptic depression induced by paired-pulse or low-frequency stimulation was
      reduced in the mutant mice. High-frequency tetanic stimulation induced lasting
      synaptic potentiation in both wild-type and mutant mice. However, the decaying
      synaptic potentiation shortly after the tetanic stimulation was significantly
      reduced in the mutant mice. These results indicate that the Shn2 deficiency
      attenuates bidirectional short-term synaptic plasticity at the MPP-GC synapse,
      thereby rendering the synapse more static. Our finding further supports a
      possible role of the dentate gyrus dysfunction in pathophysiology of
      schizophrenia and may also provide important information in interpreting
      morphology changes of the brain synapses in neuropsychiatric disorders.

PMID- 30285891
TI  - Acupuncture for irritable bowel syndrome: study protocol for a multicenter
      randomized controlled trial.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder
      characterized by abdominal pain and change of bowel habit without organic
      disease. A global perspective given by the World Gastroenterology Organization
      (WGO) points out that IBS can impact the quality of an individual's daily life,
      cause socioeconomic problems and potentially impair the patient-physician
      relationship. It remains a problem to treat IBS due to the complicated
      pathophysiology. Acupuncture is an alternative therapy recommended for IBS. The
      aim of this study is to investigate the efficacy and safety of acupuncture
      therapy for patients with IBS. We also want to explore the correlation between
      IBS-gene subtypes and acupuncture effect. METHODS/DESIGN: A multicenter
      randomized controlled trial will be performed in seven hospitals. Six hundred
      participants will be stratified into two strata (IBS-C or IBS-D). Then, patients
      within each stratum will be divided into an experimental group and a control
      group randomly. The experimental group is treated with acupuncture while the
      control group is treated with Western medicine. All the patients will receive a 6
      week treatment and a 3-month follow-up. The primary outcome is the IBS-Symptom
      Severity Score (IBS-SSS), the secondary outcome is the score of the IBS-Quality
      of Life (IBS-QoL).The correlation between IBS-gene subtypes and acupuncture
      effect will be detected based on polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP). Outcome measures (including primary and secondary
      outcome measures) are collected at baseline,1 week, 2 weeks, 4 weeks, and 6 weeks
      of the intervention, and 12 weeks after the intervention. DISCUSSION: This is a
      multicenter randomized controlled trial for IBS in China. It may clarify the
      efficacy of acupuncture as an alternative therapy for IBS. This is the first time
      ever that the potential mechanism of IBS based on genomics has been investigated.
      TRIAL REGISTRATION: Chinese Clinical Trials Register, ID: ChiCTR-IOR-15006259 .
      First registered on 14 April 2015.

PMID- 30285892
TI  - Suppression of lung cancer progression by isoliquiritigenin through its
      metabolite 2, 4, 2', 4'-Tetrahydroxychalcone.
AB  - BACKGROUND: Licorice is an herb extensively used for both culinary and medicinal
      purposes. Various constituents of licorice have been shown to exhibit anti
      tumorigenic effect in diverse cancer types. However, majority of these studies
      focus on the aspect of their growth-suppressive role. In this study, we
      systematically analyzed known licorice's constituents on the goal of identifying
      component(s) that can effectively suppress both cell migration and growth.
      METHODS: Effect of licorice's constituents on cell growth was evaluated by MTT
      assay while cell migration was assessed by both wound-healing and Transwell
      assays. Cytoskeleton reorganization and focal adhesion assembly were visualized
      by immunofluorescence staining with labeled phalloidin and anti-paxillin
      antibody. Activity of Src in cells was judged by western blot using phosphor
      Src416 antibody while Src kinase activity was measured using Promega Src kinase
      assay system. Anti-tumorigenic capabilities of isoliquiritigenin (ISL) and 2, 4,
      2', 4'-Tetrahydroxychalcone (THC) were investigated using lung cancer xenograft
      model. RESULTS: Using a panel of lung cancer cell lines, ISL was identified as
      the only licorice's constituent capable of inhibiting both cell migration and
      growth. ISL-led inhibition in cell migration resulted from impaired cytoskeleton
      reorganization and focal adhesion assembly. Assessing the phosphorylation of 141
      cytoskeleton dynamics-associated proteins revealed that ISL reduced the abundance
      of Tyr421-phosphorylation of cortactin, Tyr925- and Tyr861-phosphorylation of
      FAK, indicating the involvement of Src because these sites are known to be
      phosphorylated by Src. Enigmatically, ISL inhibited Src in cells while displayed
      no effect on Src activity in cell-free system. The discrepancy was explained by
      the observation that THC, one of the major ISL metabolite identified in lung
      cancer cells abrogated Src activity both in cells and cell-free system. Similar
      to ISL, THC deterred cell migration and abolished cytoskeleton
      reorganization/focal adhesion assembly. Furthermore, we showed both ISL and THC
      suppressed in vitro lung cancer cell invasion and in vivo tumor progression.
      CONCLUSION: Our study suggests that ISL inhibits lung cancer cell migration and
      tumorigenesis by interfering with Src through its metabolite THC. As licorice is
      safely used for culinary purposes, our study suggests that ISL or THC may be
      safely used as a Src inhibitor.

PMID- 30285895
TI  - Prevalence and associated factors of low birth weight in Axum town, Tigray, North
      Ethiopia.
AB  - OBJECTIVE: Weight at birth is a good indicator of the newborn's chances for
      survival, growth, long-term health and psychosocial development. Therefore, the
      aimed of this study is to assess the prevalence and associated factors of low
      birth weight in Axum town, Tigray, North Ethiopia. RESULT: The magnitude of low
      birth weight was 8.8%. Height of mother adjusted odds ratio (AOR) 4.607 (CI 1.34
      15.8), gestational age AOR 4.7 (CI 1.08-20.44), anti-natal care (ANC) visit AOR
      0.076 (CI 0.009-0.645), anemia during pregnancy AOR 14.5 (CI 3.821-55.6) and
      drinking alcohol AOR 6.4 (CI 1.235-33.94) were found to be significantly
      associated with low birth weight. Pre-conceptual counseling on nutrition, about
      the effect of short suture on birth outcome and personal maternal habit (drinking
      alcohol), effective treatment and prevention of anemia and awareness on the
      importance ANC follow up should be the target.

PMID- 30285894
TI  - Treatment of pustular psoriasis with anakinra: a statistical analysis plan for
      stage 1 of an adaptive two-staged randomised placebo-controlled trial.
AB  - BACKGROUND: Palmoplantar pustulosis (PPP) is a rare, chronic inflammatory skin
      disease. It is known to affect quality of life at a level comparable to that from
      major medical and psychiatric illness, yet current treatment options are
      remarkably limited. Recent evidence however suggests that interleukin-1 (IL-1)
      blockade with anakinra will deliver therapeutic benefit in PPP. METHODS: Anakinra
      for Pustular psoriasis: Response in a Controlled Trial (APRICOT) is a two-staged,
      adaptive, double-blind, randomised placebo-controlled trial which aims to test
      the hypothesis that IL-1 blockade with anakinra will deliver therapeutic benefit
      in PPP. During stage 1 a total of 24 patients will be randomised (1:1) to receive
      either placebo or anakinra. The two candidate primary outcomes are fresh pustule
      count (across palms and soles) and the Palmoplantar Pustulosis Area and Severity
      Index (PPPASI) score, recorded at baseline and at weeks 1, 4 and 8. Analysis at
      the end of stage 1 will compare treatment arms to ensure sufficient efficacy and
      safety in order to progress to stage 2. The primary outcome for stage 2 will also
      be identified following an assessment of the reliability and discriminative
      ability of fresh pustule count and PPPASI. The trial is powered to detect
      efficacy and will recruit an additional 40 patients in stage 2 (n = 64 in total).
      Analysis will follow the intention-to-treat principle and analyse patients as
      randomised. DISCUSSION: This manuscript describes the important features of the
      small population trial design for APRICOT and the pre-specified statistical
      analysis plan for stage 1. The statistical analysis plan has been developed prior
      to data extraction and in compliance with international guidelines. It will
      increase the transparency of the data analysis for the APRICOT trial. The
      findings of the trial will help to clarify the role of anakinra in the treatment
      of PPP. TRIAL REGISTRATION: ISCRTN, ISCRTN13127147 . Registered on 1 August 2016.
      EudraCT Number 2015-003600-23 . Registered on 1 April 2016.

PMID- 30285893
TI  - Radiation-induced parotid changes in oropharyngeal cancer patients: the role of
      early functional imaging and patient-/treatment-related factors.
AB  - BACKGROUND: Functional magnetic resonance imaging may provide several
      quantitative indices strictly related to distinctive tissue signatures with
      radiobiological relevance, such as tissue cellular density and vascular
      perfusion. The role of Intravoxel Incoherent Motion Diffusion Weighted Imaging
      (IVIM-DWI) and Dynamic Contrast-Enhanced (DCE) MRI in detecting/predicting
      radiation-induced volumetric changes of parotids both during and shortly after
      (chemo)radiotherapy of oropharyngeal squamous cell carcinoma (SCC) was explored.
      METHODS: Patients with locally advanced oropharyngeal SCC were accrued within a
      prospective study offering both IVIM-DWI and DCE-MRI at baseline; IVIM-DWI was
      repeated at the 10th fraction of treatment. Apparent diffusion coefficient (ADC),
      tissue diffusion coefficient Dt, perfusion fraction f and perfusion-related
      diffusion coefficient D* were estimated both at baseline and during RT. Semi
      quantitative and quantitative parameters, including the transfer constant Ktrans,
      were calculated from DCE-MRI. Parotids were contoured on T2-weighted images at
      baseline, 10th fraction and 8th weeks after treatment end and the percent change
      of parotid volume between baseline/10th fr (?Vol10fr) and baseline/8th wk.
      (?Volpost) computed. Correlations among volumetric changes and patient-,
      treatment- and imaging-related features were investigated at univariate analysis
      (Spearman's Rho). RESULTS: Eighty parotids (40 patients) were analyzed. Percent
      changes were 18.2 +/- 10.7% and 31.3 +/- 15.8% for ?Vol10fr and ?Volpost,
      respectively. Among baseline characteristics, ?Vol10fr was correlated to body
      mass index, patient weight as well as the initial parotid volume. A weak
      correlation was present between parotid shrinkage after the first 2 weeks of
      treatment and dosimetric variables, while no association was found after
      radiotherapy. Percent changes of both ADC and Dt at the 10th fraction were also
      correlated to ?Vol10fr. Significant relationships were found between ?Volpost and
      baseline DCE-MRI parameters. CONCLUSIONS: Both IVIM-DWI and DCE-MRI can help to
      detect/predict early (during treatment) and shortly after treatment completion
      the parotid shrinkage. They may contribute to clarify the correlations between
      volumetric changes of parotid glands and patient-/treatment-related variables by
      assessing individual microcapillary perfusion and tissue diffusivity.

PMID- 30285897
TI  - Fatty acid content and composition in edible Ruspolia differens feeding on
      mixtures of natural food plants.
AB  - OBJECTIVES: To develop successful mass-rearing programs of edible insects,
      knowledge of the feeds and their influence on nutritional content is critical. We
      assessed the influence of natural food plants (grass inflorescences) and their
      mixtures on fatty acid profiles of edible Ruspolia differens. We reared neonate
      nymphs to adult on six dietary treatments consisting of one, and mixtures of two,
      three, five, six and eight plants. RESULTS: The contents of saturated,
      monounsaturated and polyunsaturated fatty acids, omega-6/omega-3 ratio, and adult
      body weight did not differ among dietary treatments. However, the composition of
      fatty acids differed significantly among insects fed on six dietary treatments,
      but only for the rare fatty acids. Our results demonstrate that even if natural
      diets (grass inflorescences) do not strongly modify fatty acid contents or
      compositions of R. differens, when reared from neonate nymphs to adults, their n 
      6/n - 3 fatty acid ratio is generally low and thus good for a healthy human
      diet.

PMID- 30285896
TI  - Blocking CD248 molecules in perivascular stromal cells of patients with systemic
      sclerosis strongly inhibits their differentiation toward myofibroblasts and
      proliferation: a new potential target for antifibrotic therapy.
AB  - BACKGROUND: Fibrosis may be considered the hallmark of systemic sclerosis (SSc),
      the end stage triggered by different pathological events. Transforming growth
      factor-beta (TGF-beta) and platelet-derived growth factor BB (PDGF-BB) are
      profibrotic molecules modulating myofibroblast differentiation and proliferation,
      respectively. There is evidence linking CD248 with these two molecules, both
      highly expressed in patients with SSc, and suggesting that CD248 may be a
      therapeutic target for several diseases. The aim of this work was to evaluate the
      expression of CD248 in SSc skin and its ability to modulate SSc fibrotic process.
      METHODS: After ethical approval was obtained, skin biopsies were collected from
      20 patients with SSc and 10 healthy control subjects (HC). CD248 expression was
      investigated in the skin, as well as in bone marrow mesenchymal stem cells (MSCs)
      treated with TGF-beta or PDGF-BB, by immunofluorescence, qRT-PCR, and Western
      blotting. Finally, in SSc-MSCs, the CD248 gene was silenced by siRNA. RESULTS:
      Increased expression of CD248 was found in endothelial cells and perivascular
      stromal cells of SSc skin. In SSc-MSCs, the levels of CD248 and alpha-smooth
      muscle actin expression were significantly higher than in HC-MSCs. In both SSc-
      and HC-MSCs, PDGF-BB induced increased expression of Ki-67 when compared with
      untreated cells but was unable to modulate CD248 levels. After CD248 silencing,
      both TGF-beta and PDGF-BB signaling were inhibited in SSc-MSCs. CONCLUSIONS:
      CD248 overexpression may play an important role in the fibrotic process by
      modulating the molecular target, leading to perivascular cells differentiation
      toward myofibroblasts and interfering with its expression, and thus might open a
      new therapeutic strategy to inhibit myofibroblast generation during SSc.

PMID- 30285899
TI  - Factors associated with treatment outcome of acute post streptococcal
      glomerulonephritis among patients less than 18 years in Mekelle City, Public
      Hospitals, North Ethiopia.
AB  - OBJECTIVE: To assess factors associated treatment outcomes of acute post
      streptococcal glomerular nephritis among patients less than 18 years old in
      Mekelle City Public Hospitals. RESULTS: About 334 medical records c of children
      with acute post streptococcal glomerular nephritis were revised during the study
      period. Of these 244 (73.1%) had a positive outcome. acute post streptococcal
      glomerular nephritis was found to be statically significant associated with age <
      5 years, duration of infection, the source of infection and length of stay in
      Hospital.

PMID- 30285898
TI  - Laboratory evaluation of the efficacy of lotilaner (CredelioTM) against Amblyomma
      cajennense (sensu lato) infestations of dogs.
AB  - BACKGROUND: The ixodid tick Amblyomma cajennense (sensu lato) complex, widespread
      throughout South and Central America, is also present in Mexico, Texas and
      Florida. As a vector of Rickettsia rickettsii, and potentially of other
      pathogens, infestations with A. cajennense present a substantial health risk to
      humans, dogs and other mammals. Oral administration of lotilaner flavored
      chewable tablets (CredelioTM, Elanco) to dogs was previously shown to rapidly
      provide killing activity of infesting ticks. This study investigated lotilaner's
      efficacy against A. cajennense (s.l.). METHODS: Twenty purpose-bred Beagles (10
      male and 10 female) were ranked by Day -5 burdens of nymphal A. cajennense (s.l.)
      and randomized to either treatment with lotilaner or to a sham-treated control
      group. On Day 0, dogs were fed within approximately 30 min prior to oral
      lotilaner administration at as close as possible to 20 mg/kg, the minimum dose
      rate. For efficacy assessments, tick counts were completed 48 h post-treatment or
      48 h after experimental challenge infestations with 200 nymphal A. cajennense
      (s.l.) on Days -7, -2, 7, 14, 21 and 28. RESULTS: Tick infestations in the
      control group dogs ranged from a low of 43 to 95, with the average infestation
      remaining above 25% at each assessment, thereby meeting the requirement for
      efficacy comparison with the treated group. Lotilaner efficacy was 100% within 48
      h post-treatment, and at nine days post-treatment. Efficacy was greater than 99%
      at all subsequent assessments through Day 30. No treatment-related adverse events
      were observed. CONCLUSION: The results demonstrate that lotilaner, administered
      orally to dogs at a minimum dose of 20 mg/kg is well tolerated, provides rapid
      reduction of existing A. cajennense (s.l.) tick infestations, and provides
      sustained residual protection for at least 30 days against subsequent infestation
      by A. cajennense (s.l.).

PMID- 30285900
TI  - Swept source optical coherence tomography and optical coherence tomography
      angiography in pediatric enhanced S-cone syndrome: a case report.
AB  - BACKGROUND: Enhanced S-cone syndrome is an autosomal recessive retinal dystrophy
      related to a defect in a nuclear receptor gene (NR2E3) that leads to alteration
      in cells development from rod to S-cone. This retinal dystrophy may be associated
      with retinal schisis. The aim of this report is to describe structural optical
      coherence tomography and optical coherence tomography angiography features in a
      case of enhanced S-cone syndrome associated with macular schisis. CASE
      PRESENTATION: A Caucasian 13-year-old girl underwent measurement of best
      corrected visual acuity, ophthalmoscopic evaluation, and fundus autofluorescence
      examination. Photopic and scotopic electroretinography were carried out as well.
      Enhanced S-cone syndrome was suspected on the basis of clinical and
      electrophysiological findings. Structural optical coherence tomography and
      optical coherence tomography angiography allowed the further characterization of
      the associated macular schisis. Genetic analysis not only confirmed the diagnosis
      but increased the clinical novelty of this case report by showing two variations
      in the NR2E3 gene probably related to the phenotype: a missense variation
      c.1118T>C which leads to the substitution of leucine with proline in amino acid
      position 373, and c.349+5G>C, which involves a gene sequence near a splicing
      site. CONCLUSIONS: Swept source structural optical coherence tomography (B scans
      and "en face" images) and optical coherence tomography angiography allowed the
      observation of retinal structural details and the involvement of each retinal
      layer and capillary plexus in enhanced S-cone syndrome. Of interest, neither of
      the two NR2E3 gene variants found in this case report have been linked to any
      form of retinopathy.

PMID- 30285901
TI  - Improving research and policy interactions requires a better understanding of
      what works in different contexts.
AB  - There is keen interest in many jurisdictions in finding ways to improve the way
      that research evidence informs policy. One possible mechanism for this is to
      embed academics within government agencies either as advisers or full staff
      members. Our commentary argues that, in addition to considering the role of
      academics in government as proposed by Glied and colleagues, we need to
      understand better how research and policy interactions function across policy
      sectors. We believe more comparative research is needed to understand if and why
      academics from certain disciplines are more likely to be recruited to work in
      some policy sectors rather than others. We caution against treating government as
      monolithic by advocating the same model for collaborative interaction between
      academics and government. Lastly, we contend that contextualized research is
      needed to illuminate important drivers of research and policy interactions before
      we can recommend what is likely to be more and less effective in different policy
      sectors.

PMID- 30285902
TI  - Adoptive transfer of tumor-infiltrating lymphocytes in melanoma: a viable
      treatment option.
AB  - The treatment of metastatic melanoma patients with autologous tumor-infiltrating
      lymphocytes (TIL) shows robust, reproducible, clinical responses in clinical
      trials executed in several specialized centers over the world. Even in the era of
      targeted therapy and immune checkpoint inhibition, TIL therapy can be an
      additional and clinically relevant treatment line. This review provides an
      overview of the clinical experiences with TIL therapy thus far, including
      lymphodepleting regimens, the use of interleukin-2 (IL-2) and the associated
      toxicity. Characteristics of the TIL products and the antigen recognition pattern
      will be discussed, as well as the current and upcoming production strategies,
      including the selective expansion of specific fractions from the cell product. In
      addition, the future potential of TIL therapy in melanoma and other tumor types
      will be covered.

PMID- 30285903
TI  - Prediction of clinical outcomes in individuals with chronic low back pain: a
      protocol for a systematic review with meta-analysis.
AB  - BACKGROUND: Low back pain (LBP) is one of the most prevalent and recurrent
      conditions in the general population, with personal, professional, social and
      economic impact. However, there is a lack of consistent evidence about chronic
      low back pain (CLBP) prognosis, especially highlighting predictors that influence
      CLBP outcome. Existing systematic reviews are scarce, outdated and incomplete.
      The primary aim of this systematic review is to identify multivariable models
      and/or predictors associated with clinical outcomes in subjects with CLBP (namely
      pain intensity, disability, return to work, psychological well-being and quality
      of life). METHODS: We will systematically search Ovid MEDLINE (PubMed), Scopus
      and Web of Science databases for longitudinal studies, published until June 2017,
      including adults with CLBP (defined as persistent pain with >= 3 months
      duration), which studied the association between multivariable models and/or
      predictors with at least one of the selected clinical outcomes after >= 3 months
      of follow-up. Articles' screening and selection will be conducted by two
      reviewers, blindly and independently. Disagreements will be resolved by a third
      reviewer. Models' discriminative ability will be assessed using C-statistic. The
      link between multivariable models and predictors with the clinical outcome will
      be analysed through association measures. Qualitative and quantitative synthesis
      of the available evidence will be performed. Meta-analysis will be conducted to
      aggregate each type of measure. In the absence or in the presence of only slight
      to moderate of heterogeneity, we will use the fixed or random effects model,
      respectively. In case of moderate to severe heterogeneity, an attempt to explain
      variability in detail will be made through subgroups and sensitivity analyses.
      Subgroup analysis will be conducted according to clinical outcome, follow-up
      duration (<= 6 months versus > 6 months) and type of context (pain management
      clinics versus other therapeutic settings). DISCUSSION: We consider that it is
      urgent to highlight the available evidence about CLBP prognosis. This systematic
      review will help identify multivariable models and individual predictors that may
      enhance pain management success. One potential limitation will be the difficulty
      of aggregating quantitative measures from several prognostic models and
      predictors, with different clinical outcomes. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO CRD42017079233.

PMID- 30285904
TI  - Adult Niemann-Pick disease type C in France: clinical phenotypes and long-term
      miglustat treatment effect.
AB  - BACKGROUND: Niemann-Pick disease type C (NP-C) is a neurodegenerative lysosomal
      lipid storage disease caused by autosomal recessive mutations in the NPC1 or NPC2
      genes. The clinical presentation and evolution of NP-C and the effect of
      miglustat treatment are described in the largest cohort of patients with
      adolescent/adult-onset NP-C studied to date. METHODS: Observational study based
      on clinical chart data from adult patients with NP-C (> 18 year old) diagnosed in
      France between 1990 and 2015. Retrospective data from patients at diagnosis,
      onset of miglustat therapy (if applicable), and last follow up were analysed.
      RESULTS: In France, patients with an adolescent-adult neurological form
      constituted approximately 25% of all NP-C cases diagnosed during the study
      period. Forty-seven patients (46 with NP-C1 and one with NP-C2; 53% female) were
      included. Mean +/- SD (range) ages at neurological onset and diagnosis were 23.9
      +/- 12.5 (8-56) years and 34 +/- 13.5 (15-65) years, respectively. At
      presentation, patients mainly had 1) impaired gait due to cerebellar ataxia
      and/or dystonia, 2) and/or cognitive/behavioural manifestations, 3) and/or
      psychotic signs. Initially, almost half of patients had only one of the above
      three neuro-psychiatric manifestations. Vertical supranuclear gaze palsy, usually
      occurring without patient complaint, was only detected on careful clinical
      examination and was recorded in most patients (93%) at the time of diagnosis,
      several years after neurological onset. Thirty-seven patients (79%) received
      miglustat, among whom seventeen (46%) continued beyond 2 years (at last follow
      up) to a maximum of 9.8 years. Eight patients (22%) discontinued treatment early
      due to side effects (n = 3) or perceived lack of efficacy (n = 5).Miglustat
      treatment duration correlated significantly with reduced neurological worsening
      (p < 0.001). Treatment for>=2 years was associated with improved patient survival
      (p = 0.029). Good responses to miglustat were associated with less severe
      neurological disability at the start of miglustat treatment (p = 0.02).
      CONCLUSION: The proportion of adolescent/adult-onset NP-C cases diagnosed in
      France increased 2.5-fold since 2009 compared with the 2000-2008 period due to
      improved awareness. Adolescent/adult-onset NP-C frequently presented initially
      with a non-specific isolated neuro-psychiatric manifestation (motor, cognitive or
      psychotic). Patients with less severe neurological disability responded better to
      miglustat therapy.

PMID- 30285905
TI  - Ibuprofen supports macrophage differentiation, T cell recruitment, and tumor
      suppression in a model of postpartum breast cancer.
AB  - BACKGROUND: Women diagnosed with breast cancer within 5 years postpartum (PPBC)
      have poorer prognosis than age matched nulliparous women, even after controlling
      for clinical variables known to impact disease outcomes. Through rodent modeling,
      the poor prognosis of PPBC has been attributed to physiologic mammary gland
      involution, which shapes a tumor promotional microenvironment through induction
      of wound-healing-like programs including myeloid cell recruitment. Previous
      studies utilizing immune compromised mice have shown that blocking prostaglandin
      synthesis reduces PPBC tumor progression in a tumor cell extrinsic manner. Given
      the reported roles of prostaglandins in myeloid and T cell biology, and the
      established importance of these immune cell populations in dictating tumor
      growth, we investigate the impact of involution on shaping the tumor immune
      milieu and its mitigation by ibuprofen in immune competent hosts. METHODS: In a
      syngeneic (D2A1) orthotopic Balb/c mouse model of PPBC, we characterized the
      impact of mammary gland involution and ibuprofen treatment on the immune milieu
      in tumors and draining lymph nodes utilizing flow cytometry, multiplex IHC, lipid
      mass spectroscopy and cytokine arrays. To further investigate the impact of
      ibuprofen on programming myeloid cell populations, we performed RNA-Seq on in
      vivo derived mammary myeloid cells from ibuprofen treated and untreated
      involution group mice. Further, we examined direct effects of ibuprofen through
      in vitro bone marrow derived myeloid cell cultures. RESULTS: Tumors implanted
      into the mammary involution microenvironment grow more rapidly and display a
      distinct immune milieu compared to tumors implanted into glands of nulliparous
      mice. This milieu is characterized by increased presence of immature monocytes
      and reduced numbers of T cells and is reversed upon ibuprofen treatment. Further,
      ibuprofen treatment enhances Th1 associated cytokines as well as promotes tumor
      border accumulation of T cells. Safety studies demonstrate ibuprofen does not
      impede gland involution, impact subsequent reproductive success, nor promote auto
      reactivity as detected through auto-antibody and naive T cell priming assays.
      CONCLUSIONS: Ibuprofen administration during the tumor promotional
      microenvironment of the involuting mammary gland reduces overall tumor growth and
      enhances anti-tumor immune characteristics while avoiding adverse autoimmune
      reactions. In sum, these studies implicate beneficial prophylactic use of
      ibuprofen during the pro-tumorigenic window of mammary gland involution.

PMID- 30285907
TI  - Non-adherence to anti-tuberculosis treatment, reasons and associated factors
      among TB patients attending at Gondar town health centers, Northwest Ethiopia.
AB  - OBJECTIVE: The aim of this study was to assess the prevalence of non-adherence to
      anti-tuberculosis treatment, reasons and associated factors among TB patients
      attending at Gondar town health centers. RESULT: A total of 314 participants were
      included with the response rate of 97.5%. The mean age of participants was 35.94
      (SD +/- 13.83) years. The overall rate of non-adherence to anti-TB treatment was
      21.2% (95% CI 17.2, 26.1). Continuation phase of treatment (AOR = 2.27, 95% CI
      (1.54, 5.94)), presence of more than one co-morbidity (AOR = 6.22; 95% CI (2.21,
      17.48)), poor knowledge about TB and anti-TB therapy (AOR = 4.11; 95% CI 1.57,
      10.75), poor patient-provider relationship (AOR = 4.60, 95% CI 1.63, 12.97), and
      alcohol intake (AOR = 5.03; 95% CI 1.54, 16.40) were significantly associated
      with non-adherence. Forgetting 40 (23.1%), Being busy with other work 35 (20.2%),
      and being out of home/town 24 (13.9%) were the major reasons of participants for
      interruption of taking anti-TB medications.

PMID- 30285906
TI  - Spatial distribution and populations at risk of A. lumbricoides and T. trichiura
      co-infections and infection intensity classes: an ecological study.
AB  - BACKGROUND: Soil-transmitted helminth (STH) infections are highly prevalent in
      the Philippines. Mapping the prevalence and high-intensity of STH co-infections
      can help guide targeted intervention programmes to reduce morbidity, especially
      among vulnerable school-aged children. In this study, we aimed to predict the
      spatial distribution of the prevalence of Ascaris lumbricoides and Trichuris
      trichiura co-infection and infection intensity classes in the Philippines to
      identify populations most in need of interventions. METHODS: Data on STH
      infections from 29,919 individuals during the nationwide parasitological survey
      in 2005 to 2007 were included in the analysis. To geographically predict the
      prevalence of A. lumbricoides and T. trichiura co-infections and infection
      intensity classes, Bayesian multinomial geostatistical models were built
      including age, sex, environmental variables and a geostatistical random effect.
      The number of individuals co-infected and belonging to each of the infection
      intensity classes in 2017 was forecast by combining our predictive prevalence
      maps with population density maps. RESULTS: Our models showed that school-aged
      children (5-19 years) are most at risk of A. lumbricoides and T. trichiura co
      infections and of moderate/high infection intensity compared to other age groups.
      We identified target provinces where the likelihood of STH-associated morbidity
      was highest: Luzon (Bulacan, Benguet, Cavite, Sorsogon, Metropolitan Manila,
      Pampanga and Rizal), the Visayas (Cebu, Iloilo, Leyte and Negros Occidental), and
      in Mindanao (Agusan Del Norte, Davao Del Sur, Davao Oriental, Lanao Del Sur,
      Maguindanao, Misamis Oriental, Sulu and Zamboanga Del Sur). Luzon had the highest
      estimated number of school-aged children with A. lumbricoides and T. trichiura co
      infections (estimated total 89,400), followed by the Visayas (38,300) and
      Mindanao (20,200). CONCLUSIONS: Our study provided epidemiological evidence to
      highlight national priority areas for controlling co-infections and high
      intensity infections in the Philippines. Our maps could assist more
      geographically targeted interventions to reduce the risk of STH-associated
      morbidity in the Philippines.

PMID- 30285909
TI  - Corrigendum: Simplicispira suum sp. nov., isolated from a dust collector at a pig
      farm.

PMID- 30285908
TI  - A fragile but critical link: a commentary on the importance of government-academy
      relationships.
AB  - Interactions between government and academia can be an important support to
      effective policy and they can also ground researchers' methods and perspectives
      more strongly in the realities of policy-making and politics, leading to more
      relevant research. If properly developed, these interactions can lead to
      relationships between government and academia that re-enforce evidence-informed
      policy and useful research. However, strong relationships require repeated
      interactions and strong personal connections, something that can be supported
      through careers that cross academia and government. Academic and public service
      polices that value these kinds of careers can help build strong relationships.

PMID- 30285910
TI  - Eubacterium maltosivorans sp. nov., a novel human intestinal acetogenic and
      butyrogenic bacterium with a versatile metabolism.
AB  - A novel anaerobic, non-spore-forming bacterium was isolated from a faecal sample
      of a healthy adult. The isolate, designated strain YIT, was cultured in a basal
      liquid medium under a gas phase of H2/CO2 supplemented with yeast extract (0.1 g
      l-1). Cells of strain YIT were short rods (0.4-0.7*2.0-2.5 um), appearing singly
      or in pairs, and stained Gram-positive. Catalase activity and gelatin hydrolysis
      were positive while oxidase activity, indole formation, urease activity and
      aesculin hydrolysis were negative. Growth was observed within a temperature range
      of 20-45  degrees C (optimum, 35-37  degrees C), and a pH range of 5.0-8.0
      (optimum pH 7.0-7.5). Doubling time was 2.3 h when grown with glucose at pH 7.2
      and 37  degrees C. Besides acetogenic growth, the isolate was able to ferment a
      large range of monomeric sugars with acetate and butyrate as the main end
      products. Strain YIT did not show respiratory growth with sulfate, sulfite,
      thiosulfate or nitrate as electron acceptors. The major cellular fatty acids of
      the isolate were C16 : 0 and C18 : 0. The genomic DNA G+C content was 47.8 mol%.
      Strain YIT is affiliated to the genus Eubacterium, sharing highest levels of 16S
      rRNA gene similarity with Eubacterium limosum ATCC 8486T (97.3 %), Eubacterium
      callanderi DSM 3662T (97.5 %), Eubacterium aggregans DSM 12183T (94.4 %) and
      Eubacterium barkeri DSM 1223T (94.8 %). Considering its physiological and
      phylogenetic characteristics, strain YIT represents a novel species within the
      genus Eubacterium, for which the name Eubacterium maltosivorans sp. nov. is
      proposed. The type strain is YIT (=DSM 105863T=JCM 32297T).

PMID- 30285912
TI  - Vidian Nerve Schwannoma: A Rare Skull-Base Neoplasm Presenting with Ocular
      Manifestations: A Case Report and Literature Review.
AB  - INTRODUCTION: Vidian nerve schwannomas are exceedingly rare, with only 7 cases
      reported since 2006. Patients presenting with ocular symptoms have been reported
      in only 1 case. CASE PRESENTATION: A 54-year-old woman presented with a 3-month
      history of right periorbital pressure, third cranial nerve palsy, and visual
      field defect. Imaging results showed a right sphenoid skull-base mass with
      obliteration of the vidian canal that extended into the pterygopalatine fossa.
      The patient underwent an extended endoscopic resection with pterygopalatine fossa
      dissection. Pathologic findings demonstrated a schwannoma. DISCUSSION: A
      literature review showed that this is the second reported case of a vidian nerve
      schwannoma presenting with ocular symptoms and that endoscopic resections are
      becoming the standard of care. Practitioners should be aware that vidian nerve
      schwannomas can present as a skull-base mass with predominantly ocular symptoms,
      including vision loss, secondary to mass effect. Consideration should be given to
      this entity in the setting of typical radiographic and histopathologic
      characteristics. Endoscopic approaches to resection are safe and have low
      morbidity.

PMID- 30285911
TI  - Desertimonas flava gen. nov., sp. nov. isolated from a desert soil, and proposal
      of Ilumatobacteraceae fam. nov.
AB  - A non-motile, coccobacilli-shaped and yellow-coloured bacterium, designated
      strain SYSU D60003T, was isolated from a desert soil sample. Cells were Gram
      stain-positive, catalase-negative and oxidase-positive. The whole cell
      hydrolysates contained ll-diaminopimelic acid as the diagnostic amino acid. The
      major fatty acids were C16 : 0, summed feature 3 (C16 : 1omega7c and/or C16 :
      1omega6c) and iso-C16 : 0. The respiratory menaquinones were MK-9(H8), MK-9(H4)
      and MK-9(H6). The DNA G+C content was determined to be 70.2 % (genome). The polar
      lipids detected were diphosphatidylglycerol, an unidentified glycolipid and seven
      unidentified polar lipids. Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that strain SYSU D60003T belonged to the order Acidimicrobiales (class
      Acidimicrobiia), but formed a clade closely linked to members of the genus
      Ilumatobacter. Data from a polyphasic taxonomy study suggested that the isolate
      represents a novel species of a novel genus in the order Acidimicrobiales, for
      which the name Desertimonas flava gen. nov., sp. nov. is proposed. The type
      strain of the proposed new taxon is SYSU D60003T (=KCTC 39917T=NBRC 112924T).
      Additionally, the new taxon along with the genus Ilumatobater (family unassigned)
      were distinctly separated from the related families Acidimicrobiaceae, Iamiaceae
      and 'Microtrichaceae' in the phylogenetic trees, besides presenting a unique 16S
      rRNA gene signature nucleotides. Therefore, we propose a new family
      Ilumatobacteraceae fam. nov. within the order Acidimicrobiales to accommodate
      members of these two genera.

PMID- 30285913
TI  - Sex-Based Differences in Symptom Perception and Care-Seeking Behavior in Acute
      Stroke.
AB  - CONTEXT: Lack of early stroke recognition and delays in seeking emergency care by
      persons experiencing a stroke severely limit acute treatment options. Sparse and
      sometimes conflicting evidence suggests sex differences in care-seeking behaviors
      in stroke, stroke knowledge, perceptions of stroke symptoms, and the importance
      of physical location at the time of stroke and of having a witnessed stroke.
      OBJECTIVE: To explore specific sex-based differences in stroke presentation and
      associated care-seeking behaviors. DESIGN: Descriptive study based on a
      convenience sample of 60 patients with stroke admitted to an academic medical
      center in Northern California. MAIN OUTCOME MEASURES: Impact of the patient's sex
      on 1) time to presentation (early [<= 4.5 hours] vs late [> 4.5 hours]); 2)
      perception of symptoms and clinical signs; 3) stroke knowledge and decision
      making; 4) physical location at the time of stroke; and 5) bystander presence and
      assistance with decision making. RESULTS: There was a discrepancy between how
      patients perceive symptoms and their medical findings on physical examination.
      Although most patients had at least one sign or symptom associated with
      nationally used stroke recognition acronyms, both sexes delayed care because they
      did not perceive their symptoms as urgent. Early-presenting men were more likely
      to have a higher stroke severity score at admission, receive alteplase, arrive by
      Emergency Medical Services, and have a witnessed stroke. Both early- and late
      presenting women reported more nonfocal symptoms than did men. CONCLUSION: This
      study suggests that there are sex-based differences in symptom perception and
      care-seeking behavior in acute ischemic stroke.

PMID- 30285914
TI  - Perceptions and Experience of Patients, Staff, and Clinicians with Social Needs
      Assessment.
AB  - CONTEXT: Assessment of social needs is expanding at Kaiser Permanente (KP), but
      little is known about how members and clinicians experience the incorporation of
      social needs into health care. OBJECTIVE: To assess how KP members and clinicians
      experience social needs assessments incorporated into care. DESIGN: Qualitative
      and descriptive analysis of data from member and clinician focus groups,
      interviews, and surveys among 68 members and family caregivers who had
      participated in social needs assessment programs and 90 clinicians and staff in
      the KP Colorado, Georgia, Northern California, Northwest, and Southern California
      Regions. MAIN OUTCOME MEASURES: Members' and clinicians' perceptions and
      experiences of social needs assessment. RESULTS: Members and clinicians
      understood the impact of social needs on health and why a health care system
      representative would ask about food, housing, transportation, and other social
      needs. Members and clinicians supported social needs assessment at KP and agreed
      that KP should help address identified social needs. However, both groups
      emphasized the importance of assessments yielding actionable information. Members
      were also concerned about how the information would be used and by whom.
      CONCLUSION: Our findings support the continuing assessment of social needs at KP
      and identify issues that require attention as it expands. Assessment should not
      outpace organizational capacity to connect members with resources. Careful
      attention to communications is required because members may be uncertain or
      concerned about the purpose of the assessment and the dissemination of sensitive
      information. Messaging should assure members about data use and dissemination and
      what they can expect after screening.

PMID- 30285915
TI  - "Do You Really Need This Appointment?"

PMID- 30285916
TI  - Effect of an Electronic Alert on Targeted HIV Testing Among High-Risk
      Populations.
AB  - CONTEXT: Screening for HIV infection in medical settings remains suboptimal.
      OBJECTIVE: To examine the real-world effectiveness of an electronic clinician
      alert on the same-day HIV testing rate and early diagnosis in high-risk
      populations. DESIGN: We identified Kaiser Permanente Southern California Health
      Plan members aged 14 years or older who received tests for sexually transmitted
      infections. MAIN OUTCOME MEASURES: Encounter-based same-day HIV testing rate,
      positive test result rate, and CD4+ cell count and HIV viral load at diagnosis.
      RESULTS: We identified 1,800,948 patients who made 2,326,701 health care
      encounters eligible for HIV testing before implementation (January 1, 2008 - June
      30, 2012) and 1,362,479 eligible encounters after implementation (January 1, 2013
      - June 30, 2015). The same-day HIV testing rate increased from 36.7% to 44.1%
      (standardized mean difference = 0.15, significant difference). The alert was
      associated with a moderate difference and statistically significant increase in
      the HIV testing rate (adjusted odds ratio = 1.17, 95% confidence interval = 1.16
      1.18). The positive test result rate increased from 0.02% to 0.04% (p < 0.001).
      During the postimplementation period, fewer HIV-infected patients had a CD4+ cell
      count below 200 and/or an HIV viral load of 10,000 copies/mL or higher at
      diagnosis. CONCLUSION: Implementation of a targeted electronic alert embedded in
      the electronic medical record improved same-day HIV screening rate and positive
      test result rates among patients receiving tests for sexually transmitted
      infections in a large health organization. This intervention has potential for
      facilitating frequent screening and early identification of HIV infection in high
      risk populations.

PMID- 30285917
TI  - Cognitive Behavioral Therapy with Heart Rate Variability Biofeedback for Adults
      with Persistent Noncombat-Related Posttraumatic Stress Disorder.
AB  - OBJECTIVE: To test the effectiveness of a mental health therapy designed to
      reduce noncombat-related persistent posttraumatic stress disorder (PTSD) symptoms
      in 30 adult outpatients with a diagnosis of PTSD. The individual treatment
      offered modules to address PTSD nightmare distress, dissociation, general core
      skills, alterations in arousal and reactivity, avoidance, intrusion, and negative
      alternations in cognitions and mood. The therapeutic approach centered on
      cognitive behavioral therapy and heart rate variability biofeedback. METHODS: The
      study had 2 components: The quality improvement project that performed the
      treatment within a standard care environment, and a retrospective medical chart
      review process that analyzed the results. The Clinician-Administered PTSD Scale
      for the Diagnostic and Statistical Manual, Fifth Edition, was used to confirm the
      initial PTSD diagnosis and was the primary measure used to monitor change in the
      diagnosis following treatment. RESULTS: None of the patients who completed the
      PTSD treatment met criteria for a PTSD diagnosis in the posttreatment assessment.
      A 1-sample test of proportions, with a 95% confidence interval and a significance
      level of p < 0.05, showed p = 0.0008, and that the proportion of patients who
      would not have PTSD if the study was repeated would be 86.77% to 100.00%. The
      treatment dropout rate was 13% (4 patients). CONCLUSION: The study findings
      suggest that this intervention is an effective treatment for helping adult
      patients, including those with a history of childhood abuse, remit their PTSD
      diagnosis.

PMID- 30285918
TI  - DNR.

PMID- 30285919
TI  - The Best Year of Angela's Life.
AB  - Using a patient story, this narrative demonstrates why health care organizations,
      specifically primary care clinics, should strive to identify and to address
      social needs. This story demonstrates how Kaiser Permanente Washington, by using
      community resource specialists, has empowered primary care clinics to address
      social needs in a health care setting to improve patient care and experience.

PMID- 30285920
TI  - Different Harm and Mortality in Critically Ill Medical vs Surgical Patients:
      Retrospective Analysis of Variation in Adverse Events in Different Intensive Care
      Units.
AB  - BACKGROUND: Institutional harm reduction campaigns are essential in improving
      safe practice in critical care. Our institution embarked on an aggressive project
      to measure harm. We hypothesized that critically ill surgical patients were at
      increased risk of harm compared with medical intensive care patients. METHODS:
      Three years of administrative data for patients with at least 1 Intensive Care
      Unit day at an urban tertiary care center were assembled. Data were accessed from
      the Henry Ford Health System No Harm Campaign in Detroit, MI. Harm was defined as
      any unintended physical injury resulting from medical care. Patients were deemed
      surgical if they had at least 1 procedure in the operating room. Univariate
      analysis was used to compare surgical patients with nonsurgical. Logistic
      regression was used for risk adjustment in predicting harm and death. RESULTS:
      The study included 19,844 patients, of whom 7483 (37.7%) were surgical. The
      overall mortality was 7.8% (n = 1554). More surgical patients experienced harm
      than did nonsurgical patients (2923 [39.1%] vs 2798 [22.6%], odds ratio [OR] =
      2.2, p < 0.001). Surgical patients were less likely to die (6.2% vs 8.8%, p <
      0.001). Surgical patients were more likely to experience harm (OR = 2.1) but had
      lower mortalities (OR = 0.45) vs other harmed patients (OR = 3.8; all p < 0.001).
      CONCLUSION: Most harm in surgically critically ill patients is procedure related.
      Preliminary data show that harm is associated with death, yet both surgical and
      African American patients experience more harm with a lower mortality rate.

PMID- 30285921
TI  - Aortic root replacement with cryopreserved homograft for infective endocarditis
      in the modern North American opioid epidemic.
AB  - OBJECTIVE: To study mid-term survival in patients with infective endocarditis as
      a result of IV drug use undergoing aortic root replacement with cryopreserved
      aortic homograft. METHODS: Patients undergoing aortic root homograft replacement
      from 2011-2017 were studied retrospectively. Aortic root replacement was
      performed using a modified Bentall technique. Primary outcomes included both
      short-term and mid-term survival. Secondary outcomes included immediate
      postoperative complications. RESULTS: A total of 138 patients underwent
      cryopreserved homograft replacement of the aortic root for aortic root abscesses.
      Eighty-five patients (61.6%) underwent reoperative sternotomy, and 12 patients
      (8.7%) underwent second or third reoperative sternotomy. Sixty-seven (48.5%)
      patients had severe aortic insufficiency preoperatively. Operative mortality was
      12.3% (17 patients). Five patients (3.6%) sustained a permanent stroke. Twenty
      one patients (15.2%) required dialysis for renal failure, and 21 patients (15.2%)
      had complete heart block necessitating a permanent pacemaker. Estimated 5-year
      mortality for the cohort was 43%. CONCLUSIONS: Cryopreserved homograft
      replacement is a safe and desirable option for high-risk patients with infective
      endocarditis and aortic root abscess. Homograft accommodation for a widely
      debrided aortic annular bed provides a reasonable surgical strategy for patients
      needing aortic root replacement with annular abscess.

PMID- 30285922
TI  - [Relevance of histopathological diagnosis in the treatment of brainstem lesions
      in adults].
AB  - Brainstem tumors are uncommon beyond childhood. Controversies arise regarding the
      need of histological diagnosis in this eloquent area of the brain, weighting the
      benefits of a reliable diagnosis against the disadvantages of invasive
      procedures. There are scant publications about the surgical management of
      brainstem tumors in adults, all of them involving small retrospective cohorts. We
      are reporting our experience with the aim of contributing to the decision making
      process. Out of a series of 13 patients, 10 were approached surgically. According
      to Guillamo's classification the lesions were: focal (n:7), diffuse infiltrative
      (n:1), tectal (n:1), and exophytic (n:1). According to the Karnofsky Performance
      Status scale, the neurological status was = 70 in 6 cases and < 70 in 7.
      Histopathology was confirmed in all 10 treated cases and the samples were
      obtained by a direct microsurgical approach or by stereotactic biopsy.
      Histopathological findings were: pilocytic astrocytoma (n:1), low grade glioma
      (n:1), glioblastoma (n:1), cellular haemangioblastoma (n:1), subependimoma (n:1),
      pseudotumoral lesions (n:4; 3 cavernomas, 1 inflammatory pseudotumor), and
      disgerminoma (n:1). As a broad variety of pathologies could be found in this
      brain localization, an accurate histopathological definition can not only
      determine the adequate therapy, but also avoid the disastrous consequences of
      empiric treatments.

PMID- 30285923
TI  - [Susceptibility of Streptococcus pyogenes isolated from invasive infections to
      trimethoprim-sulfamethoxazole].
AB  - It is erroneously believed that group A streptococci (GAS) are universally
      resistant to trimethoprim-sulfamethoxazole (TMS). This is mainly because media
      commonly used for in vitro determination of susceptibility to antibiotics contain
      thymidine, a nucleoside that antagonizes the antibiotic effect of TMS. The
      objective of this work was to determine EGA sensitivity to TMS in the presence
      and absence of thymidine. To this aim, 95 GAS isolates obtained from clinical
      tissues with i nvasive infections were analyzed. Susceptibility tests were
      performed by diffusion with TMS discs in Mueller Hinton agar supplemented either
      with 5% sheep blood or with 5% lysed equine blood (MH-LEB). Lysed equine blood
      contains thymidine phosphorylase, which degrades this nucleoside. Epsilometry
      (Etest) was used as gold standard. Quality controls with Enterococcus faecalis
      strain ATCC 29212 were satisfactory with both media. A 100% sensitivity to TMS
      was found in MH-SEL whereas 6 isolates (6.3%) resulted resistant in MH-SC; only
      one of them was found to have intermediate susceptibility by Etest (MIC > 1.5/28
      upsilong/ml). The genetic determinants most frequently associated to TMS
      resistant EGA were not found in this isolate. Probably, if more accurate GAS
      specific cut-off points were established for diffusion, the correlation with
      dilution methods or with the Etest could be improved, even employing MH-SB.

PMID- 30285924
TI  - Epidemiological dynamic modeling of human papillomavirus-related diseases to
      assess vaccination strategies in Argentina.
AB  - Our objective was to develop and test a dynamic simulation model of human
      papillomavirus (HPV)-related diseases to assess rational vaccination strategies
      in Argentina. A dynamic stochastic transmission model for hetero- and homosexual
      transmission of HPV oncogenic and low-risk oncogenic types among females and
      males was developed. The model included HPV transmission and vaccination, the
      natural history of HPV-related diseases, disease outcomes, and cervical cancer
      screening. Considering all cervical cancers, covered or not by the current
      quadrivalent vaccine, the existing coverage rate would lead to 60% reduction in
      the global incidence of cervical cancer at 25 years, and to 79% at 50 years.
      Isolated current female vaccination without a screening program would need around
      100 years to eliminate cervical cancer from the local population. Current
      coverage rate would lead to 59% reduction of vulvar cancer, 76% of vaginal
      cancer, 85% of anal cancer, and 87% of oropharyngeal cancer, estimated over a 25
      year time prospect. Female HPV vaccination within the context of current cervical
      cancer screening should reach a minimum long-term mean coverage of 60% of girls,
      receiving at least a two-dose vaccine schedule, to significantly reduce or
      virtually eliminate cervical cancer at 50 years. Including vaccination to boys to
      improve herd immunity did not influence the incidence of cervical cancer over
      time, as long as female coverage did not fall below 50%. Regarding vulvar,
      vaginal, anal, penile, and some oropharyngeal cancers, current girls-only based
      vaccination could virtually eliminate these cancer types after 35-40 years, both
      in women and men.

PMID- 30285925
TI  - Cut-off values of immunological tests to identify patients at high risk of severe
      lupus nephritis.
AB  - Cut-off values for anti-dsDNA, anti-nucleosome and anti-C1q antibodies tests and
      for complementmediated hemolytic activity (CH50) were explored to identify
      patients with high risk of developing severe lupus nephritis (LN). Forty-one
      patients with confirmed systemic lupus erythematosus (SLE) were identified; their
      levels for the three antibodies and complement had been measured on a same serum
      sample. These patients were classified based on the presence of renal involvem
      ent; sixteen had active proliferative LN. With the cut-off values accepted in the
      laboratory for SLE diagnosis (anti-dsDNA > 100 UI/ml, anti-nucleosome > 50 U/ml
      or CH50 < 190 UCH50%) no significant differences were found between patients with
      and without LN. Anti-C1q > 40 U/ml showed a statistically significant association
      with LN and had 80% of specificity. Cut-off values for LN identified by Receiver
      Operating Characteristic curves (ROC) were higher for anti-dsDNA (> 455 IU/ml)
      and antinucleosome (>107 U/ml), lower for CH50 (< 150 UCH50%) and, for anti-C1q
      (> 41 U/ml) coincided with the cut-off values accepted for SLE. Anti-C1q > 134
      U/ml had a 92% of specificity, 56% of sensibility and was associated with a
      fifteen-fold increased risk of LN. The simultaneous presence of anti-nucleosome >
      107 U/ml and anti-C1q > 134 U/ml was associated with a 27-fold higher probability
      for LN. According to these results, the cut-off values used to detect SLE
      activity could be inadequate to identify patients at high risk of severe LN.

PMID- 30285926
TI  - [Immunotherapy in cancer. Current prospects, challenges and new horizons].
AB  - Recent understanding of the mechanisms that control immune system homeostasis and
      orchestrate antitumor responses has prompted the development of novel
      immunotherapeutic modalities. These include antibodies that target immune
      checkpoints such as PD-1/PD-L1 and CTLA-4, agonistic antibodies of costimulatory
      molecules such as CD137 and OX-40 and the adoptive transfer of genetically
      modified antitumor T cells. However, a large number of patients do not respond to
      these therapies and develop resistance as a result of activation of compensatory
      circuits. Rational combination of immunotherapeutic modalities will help overcome
      resistance and will increase the number of patients who will benefit from these
      treatments. Moreover, identification of predictive biomarkers will allow
      selection of patients responding to these treatments. Emerging clinical trials
      and pre-clinical studies have shown exciting results anticipating new horizons in
      the design and implementation of cancer immunotherapeutic modalities.

PMID- 30285927
TI  - [Cardiovascular risk of non-steroidal anti-inflammatory drugs].
AB  - Non-steroidal anti-inflammatories (NSAIDs) are among the most commonly used drugs
      in clinical practice. They block cyclooxygenases (COX) enzymes, but the degree of
      inhibition of COX-1 and COX-2 varies between them. In general, NSAIDs are
      classified in selective COX-2 or coxibs and non-selective or traditional NSAIDs.
      Both the analgesic and antiinflammatory effects, as well as the cardiovascular
      adverse effects, depend on the COX-2 inhibition. This paper reviews the available
      evidence of the increased risk of thrombotic events for both coxibs and
      traditional NSAID. The prothrombotic effect could be due to the inhibition of
      endothelial COX-2, with a decrease in production of prostacyclin and a relative
      increase in platelet thromboxane levels. Coxibs and diclofenac 150 mg/day seem to
      increase the risk of major vascular events by more than a third. Ibuprofen 2400
      mg/day could slightly increase the risk of coronary events. Naproxen 1000 mg/day
      apparently does not increase the risk of vascular events. Besides ibuprofen and
      naproxen have the potential to decrease the cardioprotective effect of low doses
      of aspirin. Naproxen (= 1000 mg/day) and low doses of ibuprofen (= 1200 mg/day)
      are considered to have the most favorable thrombotic cardiovascular safety
      profiles of all NSAIDs. Therapeutic decisions should be based on an assessment of
      a person's individual risk factors, using the safest NSAIDs, at the lowest
      effective doses, for the shortest duration necessary to control symptoms,
      restricting their use in patients with increased cardiovascular risk.

PMID- 30285928
TI  - [Fatal spotted fever in Salta province].
AB  - We describe the case of a 17-year-old male patient living in Salta city who, 10
      days after visiting a rural area in Salta province, was hospitalized for febrile
      seizures. Shortly after admission, he developed an exanthema followed by a
      multiple organ dysfunction that evolved to irreversible septic shock followed by
      death 48 hours after admission. Serological diagnosis -high IgM and IgG anti
      Rickettsia spp. antibody titres as detected by indirect immunofluorescence-
      arrived post mortem. Spotted fever group rickettsioses are tick-borne diseases
      distributed worldwide and continue being under diagnosed in several countries
      mainly due to a low clinical suspicion. In the north-western provinces of
      Argentina there is also the limitation of not counting with a regional laboratory
      to perform the etiological diagnosis. This is crucial because the severe forms of
      the disease, which are commonly caused by R. rickettsii, have been already
      documented in the region. Given that spotted fevers have broadly unspecific
      febrile presentations and the components of the enzootic cycle are present even
      in geographic areas not yet considered to be endemic for tick borne diseases,
      their diagnosis should not be underestimated. If the adequate antibiotic
      treatment is administered timely, the prognosis of this group of life-threatening
      diseases improves drastically.

PMID- 30285929
TI  - [Dermatomyositis associated with anti-MDA5 autoantibody].
AB  - Dematomyositis is an idiopathic inflammatory myopathy with a variable clinical
      spectrum. In recent years, a number of myositis-specific antibodies have been
      identified including anti-MDA5, which is us eful for diagnosis, prognosis and
      classification of the diverse clinical forms of the disease. This antibody is
      associated with cutaneous ulcers, rapidly progressive interstitial lung disease,
      early mortality and poor prognosis, so the detection of this antibody in a
      suitable clinical context, raises the need for an aggressive immunosuppressive
      treatment. We describe a case of dermatomyositis classified as hypomyopathic
      (i.e. involving mild muscle weakness), presenting specific skin lesions,
      interstitial lung disease, and presence of anti-MDA5 antibody that had a
      favorable response to combined treatment with cyclophosphamide, gamma globulin
      and corticosteroids.

PMID- 30285930
TI  - [Lateral medullary stroke with extracranial course of the postero- inferior
      cerebellar artery].
AB  - We present two cases of lateral medullary stroke in subjects with extracranial
      trajectory of the postero-inferior cerebellar artery. Case 1: a 21-year-old male
      who presented ataxia and right dysmetria after cervical trauma in a rugby match.
      Case 2: 56-year-old woman, who started with vertigo and left hemiparesis after
      intense physical effort. In both cases, the angiographic studies showed an
      extracranial trajectory of the posterior inferior cerebellar artery. This vessel
      rarely originates below the foramen magnum, in close relationship with the first
      three cervical vertebrae and the atlanto-axial joint. At this level, it is
      exposed to mechanical damage causing dissection, such as direct trauma, abrupt
      cervical manipulation or prolonged cephalic extension. Therefore, this
      association should be considered in patients with stroke of the lateral region of
      the bulb and extracranial trajectory of the posterior-inferior cerebellar artery.

PMID- 30285931
TI  - [Blue toe syndrome as a clinical finding of pheochromocytoma].
AB  - Pheochromocytomas are tumors that arise from chromaffin cells of the sympathetic
      nervous system and act by synthesizing and releasing catecholamines. They usually
      occur between the fourth and fifth decade of life and have a very wide clinical
      presentation. They occur only in 0.1-0.2% of the hypertensive population and
      represent a treatable and curable cause of arterial hypertension, as well as
      other symptoms derived from the uncontrolled secretion of catecholamines.
      Peripheral arterial ischemia secondary to massive amines release by a
      pheochromocytoma is a very uncommon condition. Here we report a case of
      pheochromocytoma manifested as blue finger syndrome in a patient with palpable
      distal pulses and history of poor blood pressure control despite treatment with
      two drugs.

PMID- 30285933
TI  - [Dorothy Reed, flitting pathologist].

PMID- 30285932
TI  - [Sindrome de Paget-Schrotter: presentacion de cuatro casos].
AB  - Deep vein thrombosis (DVT) of the upper limb is a rare entity, estimated to
      account for 10% of all cases of DVT. Classically, they are classified into
      primary (idiopathic, due to subclavian vein compression or exercise related) and
      secondary (cancer, thrombophilia, trauma, shoulder surgery, associated to venous
      catheters or due to hormonal causes). The Paget- Schrotter syndrome is a primary
      thrombosis of the subclavian vein in the subclavian-axillary junction, related
      either to repetitive movements or to exercise; leading to microtrauma in the
      endothelium with consequent activation of the coagulation cascade. Clinically, it
      presents abruptly with pain, edema and feeling of heaviness in the affected limb.
      The treatment varies from thrombolytics and anticoagulation to surgical
      intervention, depending on the time of evolution. We present four cases of
      exercise-related subclavian vein thrombosis.

PMID- 30285934
TI  - [Non-compliance with antiretroviral treatment and undetectable HIV viral load].

PMID- 30285935
TI  - [A hundred years of the flu: the boats that brought it].

PMID- 30285936
TI  - [Eagle syndrome: elongation of the styloid apophysis].

PMID- 30285937
TI  - [Mediastinal parathyroid adenoma detected by PET/CT with 18F choline].

PMID- 30285938
TI  - Yesterday masked, today modified; what do mycotoxins bring next?
AB  - Mycotoxins are secondary metabolites produced by toxigenic fungi in crops
      worldwide. In (micro)organisms such as plants, fungi, bacteria, or animals they
      may be further metabolised and modified, but this is also true for food
      processing, which may lead to a wide range of masked mycotoxin forms. These often
      remain undetected by analytical methods and are the culprits for underestimates
      in risk assessments. Furthermore, once ingested, modified mycotoxins can convert
      back to their parent forms. This concern has raised the need for analytical
      methods that can detect and quantify modified mycotoxins as essential for
      accurate risk assessment. The promising answer is liquid chromatography-mass
      spectrometry. New masked mycotoxin forms are now successfully detected by
      iontrap, time-of-flight, or high-resolution orbitrap mass spectrometers. However,
      the toxicological relevance of modified mycotoxins has not been fully clarified.

PMID- 30285939
TI  - Whole blood exchange transfusion as a promising treatment of aluminium phosphide
      poisoning.
AB  - A 37-year-old male was referred to us about one hour after deliberate ingestion
      of two 3-gram aluminium phosphide (ALP) tablets. Three hours after admission, his
      blood pressure dropped to 85/55 mmHg, his heart rate increased to 120 bpm, O2
      saturation dropped to 82 %, and the electrocardiogram showed junctional rhythm.
      We started whole blood exchange, and gross haematuria and jaundice ensued.
      However, his blood pressure increased, arrhythmia resolved itself, and he was
      extubated two days after the transfusion was completed. He was sent home seven
      days after admission completely symptom-free. We believe this treatment may be
      successfully applied in ALP-poisoned patients.

PMID- 30285940
TI  - How sulphur dioxide and storage temperature contribute to patulin degradation in
      homemade apple juice.
AB  - Mycotoxin patulin is one of the quality indicators for apple juice. Like other
      mycotoxins, it raises consumer health concerns. The issue of low quality is
      particularly relevant for apples provided by small producers, whose quality
      control may not be standardised. As sulphur dioxide (SO2) is common in fruit
      preservation against fungi, the aim of this study was to determine how efficient
      it is in degrading patulin in apple juices stored in real-life conditions. This
      included refrigerated (4  degrees C) and non-refrigerated warehouses/environments
      (30  degrees C) over 8, 10, 12, and 20 weeks of storage. Apple juice was diluted
      to 0.010 MUg g-1, 0.050 MUg g-1, and 0.100 MUg g-1 of patulin. SO2 was added to
      each sample in the amounts of 250 MUg mL-1 and 50 MUg mL-1. Untreated juice
      samples for each patulin concentration served as controls under the same
      experimental conditions. Patulin content was determined with high performance
      liquid chromatography. The best degradation was observed with 250 MUg mL-1 of SO2
      at 30  degrees C regardless of the patulin baseline concentration. Although
      treatment with SO2 and refrigeration did not fully remove patulin, it was highly
      efficient over twelve weeks of storage. Our results suggest that patulin levels
      can be reduced between 33 and 100 % at 30  degrees C and up to 100 % at 4 
      degrees C.

PMID- 30285941
TI  - A new approach to assessing occupational exposure to antineoplastic drugs in
      hospital environments.
AB  - Cytotoxic antineoplastic drugs (ADs) pose occupational risk and therefore require
      safe handling practices. We created, optimised, and validated an innovative
      monitoring protocol for simultaneously assessing 21 ADs in the healthcare
      environment, and also proposed surface exposure levels (SELs) to facilitate the
      interpretation of monitoring results, as there are currently no occupational
      exposure limits for ADs. The environmental AD monitoring data were collected in
      nine Italian hospitals between 2008 and 2017 and include 74,565 measurements in
      4,814 wipe samples. Excellent overall recovery and sensitivity of the analytical
      methods along with innovative desorption automation make this protocol useful for
      routine monitoring. AD contamination was found in 3,081 measurements, confirming
      potential exposure in healthcare workers. Samples taken at the beginning and the
      end of work shifts, allowed to calculate 75th and 90th percentile values for each
      ADs both in preparation and administration units and we created a traffic-light
      colour-coding system to facilitate interpretation of the findings. The
      introduction of SELs will provide a solid basis for improving occupational safety
      and focusing on contamination control.

PMID- 30285942
TI  - Clara cell protein 16 release from the nasal mucosa in allergic rhinitis, chronic
      rhinosinusitis, and exposure to air pollutants.
AB  - Clara cell protein 16 (CC16) is a small protein mainly produced by non-ciliated
      Clara cells in the respiratory epithelium. It has an anti-inflammatory role in
      chronic upper and lower airway eosinophilic inflammations. Decreased levels of
      CC16 are found in the nasal secretions and plasma of patients with chronic
      eosinophilic inflammatory disorders, such as asthma, allergic rhinitis, and
      chronic rhinosinusitis with or without nasal polyps, as well as in people exposed
      to high levels of air pollutants. Intranasal corticosteroid administration
      suppresses chronic inflammation of the nasal mucosa driven by eosinophils and
      stimulates local CC16 production. CC16 can be a reliable biomarker of the
      beneficial effects of perennial allergic rhinitis and chronic rhinosinusitis
      therapy and of the functional recovery of the nasal mucosa after treatment with
      topical glucocorticoids.

PMID- 30285943
TI  - Occupational exposure to bioburden in Portuguese bakeries: an approach to
      sampling viable microbial load.
AB  - In bakeries, a number of operations such as mixing are associated with exposure
      to air-suspended flour dust and related bioburden. The aim of this study was to
      find the best active sampling approach to the assessment of occupational exposure
      to bioburden in Portuguese bakeries based on the data obtained with the use of
      specific impaction and impinger devices. We used impaction to collect fungal
      particles from 100 L air samples onto malt extract agar (MEA) supplemented with
      chloramphenicol (0.05 %). For growing fungi we also used dichloran glycerol
      (DG18) agar-based media and for mesophilic bacteria we used tryptic soy agar
      (TSA) supplemented with nystatin (0.2 %). For Enterobacteriaceae we used violet
      red bile agar (VRBA). With impingers we also collected 300 L air samples at the
      300 L/min airflow rate, inoculated onto the same culture media. The two methods,
      impaction and impinger, showed statistically significant differences in the
      following counts: fungal on MEA (z=-2.721, p=0.007), fungal on DG18 (z=-4.830,
      p=0.000), total bacteria (z=-5.435, p=0.000), and Gram-negative coliforms (z=
      3.716, p=0.000). In all cases the impaction method detected significantly higher
      concentrations than the impinger method. Fungal and bacterial loads were higher
      in the production unit and lower in the shop. The fungal load obtained with
      impaction varied between 10 and 5140 CFU m-3, and total bacterial counts ranged
      between 10 and 4120 CFU m-3. This study has shown that the impaction method is
      the best active sampling approach to assessing viable bioburden in this specific
      occupational environment, but a multi-faceted approach to sampling and analyses
      combining methods and media enables a more refined risk characterisation and,
      consequently, better tailored risk control measures to reduce adverse health
      outcomes in workers.

PMID- 30285944
TI  - Occupational exposure to cytotoxic drugs: the importance of surface cleaning to
      prevent or minimise exposure.
AB  - Healthcare workers who prepare or administer cytotoxic agents run the risk of
      exposure, and the risks for health are real even at doses lower than those
      applied in cancer patients, because, in theory, no dose is safe. The most common
      and problematic route of exposure is through the skin, especially as work
      surfaces can remain contaminated even after cleaning. This pilot study aimed to
      demonstrate the importance of having an effective surface decontamination
      protocol by determining surface contamination with cyclophosphamide, 5
      fluorouracil, and paclitaxel as the most common cytotoxic drugs in an oncology
      day service. Samples were collected before and after drug handling and analysed
      with high performance liquid chromatography with diode array detection (HPLC
      DAD). Of the 29 samples collected before drug handling 23 were contaminated, five
      of which with more than one drug. Of the 30 samples collected after drug handling
      25 were contaminated, eight of which with more than one drug. The two time points
      did not significantly differ, which evidences a widespread contamination and
      ineffective cleaning. This calls for revising the cleaning protocol and handling
      procedure to place contamination under control as much as possible.

PMID- 30285945
TI  - Employment status of workers with a diagnosed occupational disease in Croatia: a
      10-year trend (2005-2014).
AB  - Occupational diseases (ODs) often have a chronic, progressive course, resulting
      in reduced work capacity and quality of life, prolonged sick leaves,
      unemployment, early retirements, and disability claims. The aim of this
      retrospective study was to see how diagnosed ODs affected the employment of 95
      Croatian workers between 2005 and 2014. To do that, we reviewed archived data and
      made a telephone survey. The lowest age at which an OD was diagnosed was 20 years
      in women and 22 in men, while the shortest duration of work before OD diagnosis
      was one year for both genders. The most common ODs were overuse syndromes on the
      arms, carpal tunnel syndrome in particular, diagnosed mostly in textile and
      office workers. Of the 95 participants, 12 lost their jobs since the OD
      diagnosis, 46 retired, and 37 continued to work. Significantly more participants
      became unemployed after OD diagnosis in the period 2010-2014 than 2005-2009 (9
      out of 43, 21 %, vs. 3 out of 52, 6 %, P<0.05). Only five participants were
      included in an occupational rehabilitation programme. Our findings warn against
      the deterioration in care for workers diagnosed with OD in Croatia.

PMID- 30285946
TI  - Urban honey - the aspects of its safety.
AB  - To contribute to the development of urban beekeeping, we designed this study to
      obtain more information about the contamination of urban bee products with toxic
      metals, polycyclic aromatic hydrocarbons (PAHs), and pesticides. The samples of
      honey (N=23), pollen (N=13), and floral nectar (N=6) were collected from the
      experimental stationary apiary of the Belgrade University Faculty of Agriculture
      located in centre of Zemun (a municipality of the Belgrade metropolitan area) in
      2015 and 2016. Metals (Pb, Cd, As, Cu, Zn, Fe, Mn, Ni, Cr, and Hg) were
      determined with inductively coupled plasma quadrupole mass spectrometry (ICP
      QMS). Polycyclic aromatic hydrocarbons (PAHs) were analysed with high-performance
      liquid chromatography with fluorescence detection (HPLC-FLD). Pesticides were
      analysed with gas chromatography - mass spectrometry (GC-MS). The honey samples
      were generally within the European and Serbian regulatory limits. The levels of
      all the 123 analysed pesticides were below the limit of quantification (LOQ).
      Regarding PAH levels in honey, the highest content was found for naphthalene. The
      elevated levels of Hg and Cr and of PAHs in the pollen samples indicated air
      pollution. Pesticide residues in pollen, however, were below the LOQ. In nectar,
      metal levels were relatively similar to those in honey. Our results suggest that
      the investigated urban honey meets the regulatory requirements for metals, PAHs,
      and pesticides and is therefore safe for consumption.

PMID- 30285947
TI  - Teaching about diagnostic errors through virtual patient cases: a pilot
      exploration.
AB  - BACKGROUND: Diagnostic error is a major problem in health care, yet there are few
      medical school curricula focused on improving the diagnostic process and
      decreasing diagnostic errors. Effective strategies to teach medical students
      about diagnostic error and diagnostic safety have not been established. METHODS:
      We designed, implemented and evaluated a virtual patient module featuring two
      linked cases involving diagnostic errors. Learning objectives developed by a
      consensus process among medical educators in the Society to Improve Diagnosis in
      Medicine (SIDM) were utilized. The module was piloted with internal medicine
      clerkship students at three institutions and with clerkship faculty members
      recruited from listservs. Participants completed surveys on their experience
      using the case and a qualitative analysis was performed. RESULTS: Thirty-five
      medical students and 25 faculty members completed the survey. Most students found
      the module to be relevant and instructive. Faculty also found the module valuable
      for students but identified insufficient curricular time as a barrier to
      implementation. CONCLUSIONS: Medical students and faculty found a prototype
      virtual patient module about the diagnostic process and diagnostic error to be
      educational.

PMID- 30285948
TI  - Antecedents of red cell transfusion in a large contemporary obstetric cohort.
AB  - Background Hemorrhage is a critical contributor to maternal morbidity but
      estimation of blood loss at delivery is frequently inaccurate. Due to this
      inaccuracy we sought to examine blood transfusion as a surrogate marker for
      morbidity in a large non-population based consecutive cohort. Methods A
      retrospective analysis of prospectively gathered data was carried out at two
      university institutions serving a heterogeneous urban obstetric population from
      January to December 2016. Data were analyzed to determine whether individual
      characteristics were associated with perinatal transfusion. Hematological indices
      and requirement for other blood products were also characterized. Results A total
      of 16,581 deliveries were recorded during the study and 1.7% (289/16,581) of the
      cohort required red cell transfusion. Those who received transfusion were more
      likely to be nulliparous, and to deliver <37 weeks' or >42 weeks' gestation. They
      were also more likely to have a macrosomic infant (birthweight >4 kg) and to have
      had a multiple pregnancy. Characteristics not associated with risk of transfusion
      included obesity [18% (52/289) vs. 15% (2445/16,292); P=0.18], and maternal age
      >=35 years [28% (82/289) vs. 33% (5537/16,292); P=0.05]. Additional blood
      products were necessary in a small number of patients who received red cells.
      Conclusions The rate of transfusion in a contemporary Irish cohort has risen
      compared with previous data. Several variables associated with transfusion are
      consistent with older studies but importantly; maternal obesity and advanced
      maternal age are not associated with transfusion. These data may encourage the
      investment of resources in a population previously considered low-risk and,
      following future studies, to improve strategies aimed at limiting blood
      transfusion.

PMID- 30285949
TI  - Lifting with straight legs and bent spine is not bad for your back.

PMID- 30285950
TI  - A review of potential factors contributing to epidemic cholera in Yemen.
AB  - The menace of cholera epidemic occurrence in Yemen was reported in early 2017.
      Recent reports revealed that an estimated 500,000 people are infected with
      cholera whereas 2,000 deaths have been reported in Yemen. Cholera is transmitted
      through contaminated water and food. Yemen is the least developed country among
      the Middle East countries in terms of wastewater and solid waste management. The
      population of Yemen is about 24.5 million and generates about 70-100 million m3
      of sewage. An estimated 7% of the population has sewerage systems. It has been
      revealed that 31.2 million m3 of untreated sewage is used for irrigation purposes
      especially for vegetables and Khat trees. In addition, more than 70% of the
      population in Yemen has no potable water. They depend on water wells as a water
      source which are located close to sewage disposal sites. The present review
      focuses on the current status of water, wastewater as well as solid waste
      management in Yemen and their roles in the outbreak of cholera. Future prospects
      for waste management have been proposed.

PMID- 30285951
TI  - Natural organic matter as precursor to disinfection byproducts and its removal
      using conventional and advanced processes: state of the art review.
AB  - Natural organic matter (NOM) is ubiquitous in the aquatic environment and if
      present can cause varied drinking water quality issues, the major one being
      disinfection byproduct (DBP) formation. Trihalomethanes (THMs) are major classes
      of DBP that are formed during chlorination of NOM. The best way to remove DBPs is
      to target the precursors (NOM) directly. The main aim of this review is to study
      conventional as well as advanced ways of treating NOM, with a broad focus on NOM
      removal using advanced oxidation processes (AOPs) and biofiltration. The first
      part of the paper focuses on THM formation and removal using conventional
      processes and the second part focuses on the studies carried out during the years
      2000-2018, specifically on NOM removal using AOPs and AOP-biofiltration.
      Considering the proven carcinogenic nature of THMs and their diverse health
      effects, it becomes important for any drinking water treatment industry to
      ameliorate the current water treatment practices and focus on techniques like AOP
      or synergy of AOP-biofiltration which showed up to 50-60% NOM reduction. The use
      of AOP alone provides a cost barrier which can be compensated by the use of
      biofiltration along with AOP with low energy inputs, making it a techno
      economically feasible option for NOM removal.

PMID- 30285952
TI  - Sick leave due to diarrhea caused by contamination of drinking water supply with
      Cryptosporidium hominis in Sweden: a retrospective study.
AB  - We investigated sick leave from work, studies, preschool, and kindergarten
      occurring between 1 November 2010 and 31 January 2011 and associated with a
      waterborne outbreak of diarrhea caused by Cryptosporidium hominis in late
      November 2010 in Ostersund, Sweden with 45.2% of 60,000 residents being
      symptomatic. A questionnaire defining acute watery diarrhoea and/or >=3 diarrhea
      episodes/day as cryptosporidiosis was sent to 1,508 residents in late January
      2011 (response rate 69.2%). Among adults aged 18-60 years, 24.0% took sick leave
      for a mean of 4.6 (SD +/- 4.0) days due to cryptosporidiosis, and an additional
      10.6% were absent from work a mean of 4.0 (+/-2.2) days to care for symptomatic
      children. Among children (aged <=17 years), 35.0% stayed home sick from
      kindergarten/preschool or school/university for a mean of 5.2 (+/-3.8) days
      resulting in 5.1 (+/-4.4) days of absence from work per sick child shared between
      parents/guardians. The estimated total number of sick leave days was 50,000 for
      adults and 20,700 for children, with an estimated direct cost of ?7 million for
      employers. The potential impact on society of sick leave caused by waterborne
      diseases must be considered in decisions regarding the quality of drinking water.

PMID- 30285953
TI  - Categorical performance characteristics of method ISO 7899-2 and indicator value
      of intestinal enterococci for bathing water quality monitoring.
AB  - Intestinal enterococci indicate the fecal contamination of bathing waters. This
      study defines the performance characteristics of the reference method ISO 7899
      2:2000 with water samples collected from inland and coastal bathing areas in
      Finland. From a total of 341 bacterial isolates grown on Slanetz and Bartley
      medium, 63.6% were confirmed as intestinal enterococci on bile aesculin agar. The
      partial 16S rRNA gene sequences showed that Enterococcus faecium and Enterococcus
      faecalis clades accounted for 93.1% of the confirmed isolates. The range of the
      false positive and false negative rate of the ISO 7899-2 was 0.0-18.5% and 5.6
      57.1%, respectively, being affected by the presumptive colony count on the
      membrane. The analysis of multiple sample volumes is proposed to reach 10-100
      colonies per membrane when 47 mm diameter membranes are used to prevent
      overestimation of low counts and underestimation of the high counts.

PMID- 30285954
TI  - Association of water quality with soil-transmitted helminthiasis and diarrhea in
      Nueva Santa Rosa, Guatemala, 2010.
AB  - Improved water quality reduces diarrhea, but the impact of improved water quality
      on Ascaris and Trichuris, soil-transmitted helminths (STH) conveyed by the fecal
      oral route, is less well described. To assess water quality associations with
      diarrhea and STH, we conducted a cross-sectional survey in households of south
      eastern Guatemala. Diarrhea was self-reported in the past week and month. STH was
      diagnosed by stool testing using a fecal parasite concentrator method. We
      explored associations between Escherichia coli-positive source water (water
      quality) and disease outcomes using survey logistic regression models. Overall,
      732 persons lived in 167 households where water was tested. Of these, 79.4%
      (581/732) had E. coli-positive water, 7.9% (58/732) had diarrhea within the week,
      14.1% (103/732) had diarrhea within the month, and 6.6% (36/545) tested positive
      for Ascaris or Trichuris, including 1% (6/536) who also reported diarrhea.
      Univariable analysis found a statistically significant association between water
      quality and STH (odds ratio [OR] = 5.1, 95% confidence interval [CI] = 1.1-24.5)
      but no association between water quality and diarrhea. Waterborne transmission
      and effects of water treatment on STH prevalence should be investigated further.
      If a causal relationship is found, practices such as household water treatment
      including filtration might be useful adjuncts to sanitation, hygiene, and
      deworming in STH control programs.

PMID- 30285955
TI  - Assessment of the parasitological quality of water stored in private cisterns in
      rural areas of Tunisia.
AB  - Limited access to safe water enhances poverty, hunger and diseases. This study
      evaluated the drinking water quality stored in home-based systems, located in
      rural areas of Tunisia. Water management was also documented as an improvement of
      good practice as most of the water contamination could be related to behavioral
      patterns. Thirty-nine water samples from five different sources (rainwater, truck
      cistern, mix, etc.) were screened for enteric parasitic contamination with the
      modified Bailenger technique. This technique allowed the detection of three
      protozoa: Giardia spp.; Entamoeba histolytica/dispar/moshkovskii; Entamoeba coli
      and one helminth specie: Ascaris spp. The overall prevalence of these intestinal
      parasites was approximately 97% with a relatively high frequency of protozoa over
      helminths and more specifically E. histolytica/dispar/moshkovskii. This incidence
      could be correlated to the lack of hygiene practices, sanitation and education.
      This situation requires the need for frequent monitoring of the water quality and
      management in these areas.

PMID- 30285956
TI  - Computational fluid dynamics analysis of the hydraulic (filtration) efficiency of
      a residential swimming pool.
AB  - Hydraulic or filtration efficiency of residential swimming pools, quantified in
      terms of residence time characteristics, is critical to disinfection and thus
      important to public health. In this study, a three-dimensional computational
      fluid dynamics model together with Eulerian and Lagrangian-based techniques are
      used for investigating the residence time characteristics of a passive tracer and
      particles in the water, representative of chemicals and pathogens, respectively.
      The flow pattern in the pool is found to be characterized by dead zone regions
      where water constituents may be retained for extended periods of times, thereby
      potentially decreasing the pool hydraulic efficiency. Two return-jet
      configurations are studied in order to understand the effect of return-jet
      location and intensity on the hydraulic efficiency of the pool. A two-jet
      configuration is found to perform on par with a three-jet configuration in
      removing dissolved constituents but the former is more efficient than the latter
      in removing or flushing particles. The latter result suggests that return-jet
      location and associated flow circulation pattern have an important impact on
      hydraulic efficiency. Thus return-jet configuration should be incorporated as a
      key parameter in the design of swimming pools complementing current design
      standards.

PMID- 30285957
TI  - Faecal contamination in public pools in Barcelona province: Cryptosporidium spp.
      and bacterial indicators.
AB  - A study was conducted of the occurrence of Cryptosporidium in indoor heated
      public swimming pools and of three bacterial indicators (Escherichia coli, faecal
      enterococci and Clostridium perfringens) on pool surrounds. Although all examined
      pools adhered strictly to the Spanish regulations, the influence of several
      parameters related to water conditions, pool structure, users and location on the
      presence of protozoa and bacteria was analysed. Cryptosporidium was detected in
      18.8% of pools in 60% of the five towns studied. The maximum concentration was 13
      oocysts/L in one swimming pool and one Jacuzzi. The bacterial indicators'
      prevalence on pool surrounds was higher than 50%, being present in all of the
      towns. Plastic surfaces presented the lowest bacterial prevalence, whereas
      painted surfaces were 100% positive. No differences were observed for pool
      surrounds with autonomous or disabled users. Risk of cryptosporidiosis in pool
      vessels indicated that concentrations over 1 oocyst/10 L enhance the risk of
      infection, even in one exposure. Guidelines for managing faecal accidents and
      public information on the importance of good hygiene behaviours in and around
      swimming pools are recommended to limit oocysts' presence.

PMID- 30285958
TI  - Photocatalytic degradation of reactive black 5 on the surface of tin oxide
      microrods.
AB  - A simple co-precipitation technique is proposed for synthesis of tin oxide (SnO2)
      microrods. Stannous chloride and urea were used during synthesis. X-ray powder
      diffraction (XRD) analysis revealed that the annealed product consists of SnO2
      microrods having tetragonal unit cells, while scanning electron microscopy (SEM)
      analysis revealed the rod-like morphology of a synthesized product. These
      synthesized microrods are used as photocatalyst for the degradation of reactive
      black 5 (RB5). Degradation kinetics of RB5 are monitored under daylight in
      different concentrations of hydrogen peroxide (H2O2) and catalyst. The percentage
      of RB5 conversion is also calculated at various concentrations of hydrogen
      peroxide and catalyst which demonstrate that RB5 shows high catalytic degradation
      at high concentrations of hydrogen peroxide and catalyst.

PMID- 30285959
TI  - Contamination of arsenic, manganese and coliform bacteria in groundwater at
      Kushtia District, Bangladesh: human health vulnerabilities.
AB  - Safe water is essential for life. Consumption of arsenic and manganese
      contaminated water poses a range of health effects to humans. Physico-chemical
      and bacteriological characteristics of groundwater at five administrative
      upazillas in Kushtia District, Bangladesh, have been studied to evaluate the
      potability of water for drinking purpose from 32 randomly selected tube wells
      (TWs). APHA (2012) standard analytical methods were applied for analyses of the
      physico-chemical and bacteriological parameters of the water samples. Arsenic,
      iron, and manganese content were analyzed by atomic absorption spectroscopy
      (AAS). The investigated parameters of water samples were found as pH 6.81-8.12,
      electrical conductivity (EC) 520-1,995 MUs/cm, total dissolved solids (TDS) 357.8
      1,372.6 mg/L, chloride 10-615 mg/L, total hardness 285-810 mg/L, arsenic (As)
      0.001-0.098 mg/L, iron (Fe) 0.04-1.45 mg/L, manganese (Mn) 0.01-6.32 mg/L. About
      56.25% of TWs were highly contaminated with fecal coliform (FC) and 68.75% were
      found to be contaminated with total coliform (TC). Results were compared with
      World Health Organization (WHO) and Bangladesh Drinking Standards (BDS). The
      concentrations of water quality parameters are much higher as compared to WHO and
      BDS standards. This may cause acute public health risks and make water unsuitable
      for direct human consumption without treatment.

PMID- 30285960
TI  - Ultraviolet A and B wavelength-dependent inactivation of viruses and bacteria in
      the water.
AB  - UVA and UVB can be applied to solar disinfection of water. In this study, the
      inactivation and photoreactivation of viruses and bacteria in the UVA-B range
      were analyzed. MS2 and T4 bacteriophages, and Escherichia coli were used as
      surrogates to quantify dose-response behaviors. Inactivation in UVC was used to
      validate the methodology and to expand the inactivation action spectra. The
      results showed log-linear inactivation for MS2 and T4 in the 254-320 nm
      wavelength range. T4 inactivation was consistently faster than MS2 (except at 320
      nm), and for both phages, inactivation decreased with increasing wavelength. The
      dose-response of bacteria exhibited a lag at low doses, possibly because the
      photons must strike a discrete number of critical targets before growth stops. A
      tail was present at high doses for some wavelengths, perhaps due to clumping or
      the presence of subgroups with higher resistance. The inactivation action spectra
      for bacteria exhibited a reduction in inactivation as wavelength increased. No
      bacterial inactivation was observed beyond 320 nm at doses applied. After
      inactivation at 297 nm (UVA), bacteria regained viability through
      photoreactivation, and repair increased with increase in photoreactivating light
      exposure time. This implies additional doses above inactivation thresholds are
      required to cause irreversible damage. These results are useful for designing
      solar disinfection systems.

PMID- 30285961
TI  - Isolation and molecular identification of Acanthamoeba spp. from hot springs in
      Mazandaran province, northern Iran.
AB  - Acanthamoeba is a free-living protozoan that can be found in natural and
      artificial environments such as hot tubs, surface water and springs and can cause
      severe diseases including amoebic keratitis and granulomatous amoebic
      encephalitis. The present study was conducted owing to the lack of research
      regarding genotypes of Acanthamoeba in hot springs of Mazandaran province in
      northern Iran. Twenty-four water samples were collected from all hot springs in
      Mazandaran province. After filtration through nitrocellulose membrane, samples
      were cultured on non-nutrient agar medium enriched with TYIS-33. The cultures
      were microscopically examined for the presence of Acanthamoeba. Positive cultures
      were analysed by polymerase chain reaction (PCR) and genotypes were determined by
      targeting the 18 S rRNA gene. The pathogenic potential of all positive isolates
      was identified using thermotolerance and osmotolerance tests. Eleven (47.8%)
      samples were positive for Acanthamoeba. Based on sequencing analysis, 100% of
      isolates belonged to the T4 genotype. Thermo- and osmo-tolerance tests showed
      that four (36.3%) Acanthamoeba strains were highly pathogenic. According to our
      research, the occurrence of Acanthamoeba in recreational hot springs could be a
      hazard for high risk persons. Posting warning signs and regular monitoring of
      these waters by health planners may therefore be useful for decreasing
      Acanthamoeba spp. infections.

PMID- 30285962
TI  - Preparation, adsorptive properties and chemical regeneration studies of high
      porous activated carbon derived from Platanus orientalis leaves for Cr(VI)
      removal.
AB  - Activated carbon (AC) was prepared from Platanus orientalis leaves by H3PO4
      activation using a microwave heating method and characterized by SEM (scanning
      electron microscopy), Brunauer-Emmett-Teller (BET) surface area analysis and FTIR
      (Fourier transform infrared spectroscopy) techniques. AC exhibited a surface area
      of 1089.67 m2/g and a relatively high pore volume of 1.468 cm3/g. Utilization of
      AC for the removal of Cr(VI) from aqueous solution was researched. The adsorption
      efficiency was highly pH dependent and adsorption capacity of AC for Cr(VI) could
      reach up to 135.24 mg/g. Adsorption equilibrium could be quickly reached within 2
      h. A kinetic study indicated that the adsorption of Cr(VI) conformed to the
      pseudo-second-order model (R2 > 0.99). An intraparticle diffusion model was
      applied to describe the adsorption kinetics, and the results showed that there
      are other factors that affect the rate. Chemical regeneration for AC saturated
      with Cr(VI) was performed and HNO3 displayed the best regeneration performance
      among the four chemical regeneration agents (HNO3, H2SO4, NaOH, NaCl). The
      regeneration performance increased at first and then decreased with the rise of
      HNO3 concentration, and regeneration reaction could reach equilibrium within 4 h
      in the first cycle. The FTIR spectra revealed that HNO3 successfully introduced N
      H bonds onto the AC surface in the regeneration process.

PMID- 30285963
TI  - Drinking water in West Virginia (USA): tap water or bottled water - what is the
      right choice for college students?
AB  - West Virginia has had a history of water quality issues. In parallel, the world
      is facing a plastic pollution crisis. In order to better understand behavioral
      responses to perceived water quality, a survey was conducted at a major research
      university to ask participants about water quality perceptions and drinking water
      behaviors. A total of 4,188 students completed the survey during the Spring 2017
      semester. Logistic regression analyses were used to predict behaviors. Results
      indicated that a third of the student population primarily used bottled water for
      drinking purposes at home, while 39% used a filter at home and 26% drank water
      directly from the tap. On campus, bottled water use was reported by 36% of the
      students, water fountain use represented 31%, and 29% of the students brought
      their own water with reusable cups/bottles. Health risk perceptions, organoleptic
      perceptions (i.e., taste, odor, color), and environmental concern were predictors
      of the different behaviors. Students originally from West Virginia had a higher
      propensity of using bottled water. We argue that bottled water consumption should
      be reduced in areas where water quality is not an issue. In this sense, there is
      a need for education among the student population in West Virginia.

PMID- 30285964
TI  - Monitoring levels of viable Helicobacter pylori in surface water by qPCR in
      Northeast Spain.
AB  - Helicobacter pylori infection is a risk factor for chronic active gastritis,
      peptic ulcers, gastric carcinoma and lymphoma. Although the infection may be
      acquired through different transmission routes, the presence and viability of H.
      pylori in water sources are not well known. Therefore, the aim of our study was
      to analyse the viability of H. pylori cells in urban surface waters collected at
      the Vallparadis public park in Terrassa, Barcelona, Spain. The water samples were
      analysed by viability quantitative polymerase chain reaction (qPCR) using
      propidium monoazide and specific primers for the H. pylori vacuolating cytotoxin
      (vacA gene). Viable H. pylori were found in 91.3% of the samples analysed, with
      an average concentration of 3.46 +/- 1.06 log cell 100 mL-1. Our work proves a
      quick and simple procedure for evaluating viable H. pylori cells in environmental
      samples by qPCR. Furthermore, the results provide evidence that urban surface
      waters may contain considerable levels of viable H. pylori cells, thus indicating
      they are a potential source of infection, which represents a public health
      concern.

PMID- 30285965
TI  - Degradation of rhodamine B with manganese dioxide nanorods.
AB  - This is an investigation on oxidative degradation of rhodamine B (RhB) by
      manganese dioxide (MnO2) nanorods synthesized by redox co-precipitation method.
      Field emission scanning electron microscopy of MnO2 nanorods at an electron
      voltage of 10 kV revealed a rod-like morphology for the synthesized
      nanoparticles. Fourier transform infrared spectra exhibited characteristic peaks
      of MnO2. Surface area of MnO2 nanorods was 277 m2/g. Effect of various parameters
      like initial concentration and pH of RhB solution, time of contact between MnO2
      nanorods and RhB, dosage of MnO2, and stirring speed on decolouration of RhB was
      evaluated in batch experiments. Rapid decolouration in the initial period of the
      reaction was observed due to the adsorption of RhB molecules onto the surface of
      MnO2 nanorods followed by oxidative degradation. Percentage decolouration
      decreased with increase in initial concentration and increased with increase in
      dosage, speed of stirring the mixture and with increase in pH up to pH 7. Near
      complete decolouration was achieved at a dose of 0.5 g/L of MnO2 nanorods from 20
      mg/L RhB solution within 3 min. Observations fitted best to the pseudo second
      order kinetic model. This study could pave the way for development of cost
      effective, nontoxic nanostructures for treatment of wastewaters containing RhB.

PMID- 30285966
TI  - Molecular surveillance of Cryptosporidium and Giardia duodenalis in sludge and
      spent filter backwash water of a water treatment plant.
AB  - The purpose of this study was to monitor the presence of Cryptosporidium spp. and
      Giardia duodenalis in a water treatment plant (WTP) using settling sludge and
      backwash water (BW) samples in previous and post the deflocculation of
      polyaluminium chloride (PAC) flacks. Eleven collections were performed. BW and
      settling sludge (SSF) were concentrated by calcium carbonate flocculation, and
      another aliquot of settling sludge (SSC) by centrifugation. The samples were
      divided as follows: Group A, containing 33 samples without degradation of PAC
      flakes, and Group B, with degradation by alkalinization with 10 M NaOH. Sample
      DNA was extracted with a commercial kit, and nested polymerase chain reaction
      (PCR) was used to detect Cryptosporidium and G. duodenalis. All samples from
      Group A were negative for Cryptosporidium spp., and 6.1% (2/33) were positive for
      G. duodenalis in SSC samples. While the absence of Cryptosporidium may be due to
      a low contamination level of the water resource, the presence of G. duodenalis
      indicates contamination of the raw water. The detection of G. duodenalis in SSC
      samples indicates that this detection method was the most effective. The 33
      samples from Group B were negative for both protozoa, probably due to the
      presence of aluminium and humic substances.

PMID- 30285967
TI  - Erythromelalgia and Peripheral Nerve Block: A Case Report.
AB  - A 79-year-old woman with primary erythromelalgia underwent a left reverse total
      shoulder arthroplasty with a left interscalene nerve block, a superficial
      cervical plexus block, and a general endotracheal anesthetic, with no residual
      neurological deficits. Herein, we discuss the classification and pathophysiology
      of erythromelalgia along with the anesthetic considerations of peripheral nerve
      blockade in patients with primary erythromelalgia.

PMID- 30285968
TI  - Anesthesia Experience for Tonsillectomy in a Patient With Hypofibrinogenemia: A
      Case Report.
AB  - A 26-year-old male patient with hypofibrinogenemia was scheduled to undergo
      tonsillectomy. Hypofibrinogenemia, defined as low plasma fibrinogen (Fbg)
      concentration, is a type of congenital Fbg deficiency and is a rare coagulopathy.
      Perioperative replenishment of Fbg is performed during minor surgeries, aimed at
      maintaining plasma Fbg concentrations of 50 mg/dL. In this case, failure to
      replenish Fbg during the postoperative period may have caused the postoperative
      hemorrhage. Considering the half-life of Fbg (3-4 days), the plasma Fbg
      concentration should be monitored for >=6 postoperative days, aiming at a target
      level of 50 mg/dL during the postoperative period.

PMID- 30285969
TI  - Anesthetic Implications of a Patient With Kniest Dysplasia and Mitochondrial
      Disease: A Case Report.
AB  - Kniest dysplasia, or metatropic dysplasia type II, is a rare chondrodysplasia
      caused by abnormal type II collagen. Clinically, it is characterized by dwarfism,
      deafness, skeletal derangements, and ocular abnormalities. Mitochondrial diseases
      produce a spectrum of abnormalities in affected individuals and predominantly
      impact organs of high energy utilization, including the brain, skeletal muscles,
      kidneys, and liver. We present the case of a 6-year-old boy with both Kniest
      dysplasia and underlying mitochondrial disease for examination under anesthesia
      before cataract surgery. Successful anesthetic management of a patient with
      Kniest dysplasia and a mitochondrial myopathy is discussed.

PMID- 30285970
TI  - Are Epidural Steroid Injections Beneficial for Patients With Degenerative Lumbar
      Spondylolisthesis?

PMID- 30285971
TI  - Blood Products in the Management of Abnormal Placentation.
AB  - A critical tool in the successful management of patients with abnormal
      placentation is an established massive transfusion protocol designed to rapidly
      deliver blood products in obstetrical and surgical hemorrhage. Spurred by trauma
      research and an understanding of consumptive coagulopathy, the past 2 decades
      have seen a shift in volume resuscitation from an empiric, crystalloid-based
      method to balanced, targeted transfusion therapy. The present article reviews
      patient blood management in abnormal placentation, beginning with optimizing the
      patient's status in the antenatal period to the laboratory assessment and
      transfusion strategy for blood products at the time of hemorrhage.

PMID- 30285972
TI  - Gender-Affirming Hormone Therapy for Transgender Men.
AB  - There are an estimated 1.4 million transgender adults in the United States, and
      lack of providers knowledgeable in transgender care is a barrier to health care.
      Obstetricians and Gynecologists can help increase access in part by becoming
      competent in gender-affirming hormone therapy. For transgender men, testosterone
      protocols can be extrapolated from those used for hypogonadal cisgender men.
      Unfortunately, there are not any high-quality, long-term prospective studies on
      the effectiveness and safety of different testosterone regimens specifically in
      transgender men, but the available data suggest that gender-affirming
      testosterone therapy is safe and effective with proper screening and monitoring.

PMID- 30285973
TI  - Foreword: Caring for Lesbians, Bisexual Women, Transgender, and Gender
      Nonconforming People.

PMID- 30285974
TI  - Clinical Care of Lesbian and Bisexual Women for the Obstetrician Gynecologist.
AB  - Sexual minority women are more likely to delay care, less likely to have a usual
      place of care, and more likely to exhibit higher risk behaviors such as smoking,
      obesity, heavy drinking resulting in a disproportionate number of chronic
      conditions. It is imperative for obstetrician-gynecologists to be at the
      forefront of providing comprehensive health care to all women, no matter their
      sexual orientation. This article seeks to discuss health care disparities as well
      as health behaviors and outcomes in this population. In addition, it will review
      the appropriate recommendations for clinical care of sexual minority women for
      the obstetrician/gynecologist.

PMID- 30285975
TI  - Association Between Multidisciplinary Management of Hepatocellular Carcinoma and
      Patient Survival.

PMID- 30285976
TI  - Recent Trends and the Impact of the Affordable Care Act on Emergency Department
      Visits and Hospitalizations for Gastrointestinal, Pancreatic, and Liver Diseases.
AB  - BACKGROUND: The Affordable Care Act (ACA) with Medicaid expansion implemented in
      2014, extended health insurance to >20-million previously uninsured individuals.
      However, it is unclear whether enhanced primary care access with Medicaid
      expansion decreased emergency department (ED) visits and hospitalizations for
      gastrointestinal (GI)/pancreatic/liver diseases. METHODS: We evaluated trends in
      GI/pancreatic/liver diagnosis-specific ED/hospital utilization over a 5-year
      period leading up to Medicaid expansion and a year following expansion, in
      California (a state that implemented Medicaid expansion) and compare these with
      Florida (a state that did not). RESULTS: From 2009 to 2013, GI/pancreatic/liver
      disease ED visits increased by 15.0% in California and 20.2% in Florida and
      hospitalizations for these conditions decreased by 2.6% in California and
      increased by 7.9% in Florida. Following Medicaid expansion, a shift from self
      pay/uninsured to Medicaid insurance was seen California; in addition, a new
      decrease in ED visits for nausea/vomiting and GI infections, was evident, without
      associated change in overall ED/hospital utilization trends. Total
      hospitalization charges for abdominal pain, nausea/vomiting, constipation, and GI
      infection diagnoses decreased in California following Medicaid expansion, but
      increased over the same time-period in Florida. CONCLUSIONS: We observed a
      striking payer shift for GI/pancreatic/liver disease ED visits/hospitalizations
      after Medicaid expansion in California, indicating a shift in the reimbursement
      burden in self-pay/uninsured patients, from patients and hospitals to the
      government. ED visits and hospitalization charges decreased for some primary care
      treatable GI diagnoses in California, but not for Florida, suggesting a trend
      toward lower cost of gastroenterology care, perhaps because of decreased hospital
      utilization for conditions amenable to outpatient management.

PMID- 30285977
TI  - Bimodal Hearing or Bilateral Cochlear Implants? Ask the Patient.
AB  - OBJECTIVE: The objectives of this study were to assess the effectiveness of
      various measures of speech understanding in distinguishing performance
      differences between adult bimodal and bilateral cochlear implant (CI) recipients
      and to provide a preliminary evidence-based tool guiding clinical decisions
      regarding bilateral CI candidacy. DESIGN: This study used a multiple-baseline,
      cross-sectional design investigating speech recognition performance for 85
      experienced adult CI recipients (49 bimodal, 36 bilateral). Speech recognition
      was assessed in a standard clinical test environment with a single loudspeaker
      using the minimum speech test battery for adult CI recipients as well as with an
      R-SPACE 8-loudspeaker, sound-simulation system. All participants were tested in
      three listening conditions for each measure including each ear alone as well as
      in the bilateral/bimodal condition. In addition, we asked each bimodal listener
      to provide a yes/no answer to the question, "Do you think you need a second CI?"
      RESULTS: This study yielded three primary findings: (1) there were no significant
      differences between bimodal and bilateral CI performance or binaural summation on
      clinical measures of speech recognition, (2) an adaptive speech recognition task
      in the R-SPACE system revealed significant differences in performance and
      binaural summation between bimodal and bilateral CI users, with bilateral CI
      users achieving significantly better performance and greater summation, and (3)
      the patient's answer to the question, "Do you think you need a second CI?" held
      high sensitivity (100% hit rate) for identifying likely bilateral CI candidates
      and moderately high specificity (77% correct rejection rate) for correctly
      identifying listeners best suited with a bimodal hearing configuration.
      CONCLUSIONS: Clinics cannot rely on current clinical measures of speech
      understanding, with a single loudspeaker, to determine bilateral CI candidacy for
      adult bimodal listeners nor to accurately document bilateral benefit relative to
      a previous bimodal hearing configuration. Speech recognition in a complex
      listening environment, such as R-SPACE, is a sensitive and appropriate measure
      for determining bilateral CI candidacy and also likely for documenting bilateral
      benefit relative to a previous bimodal configuration. In the absence of an
      available R-SPACE system, asking the patient whether or not s/he thinks s/he
      needs a second CI is a highly sensitive measure, which may prove clinically
      useful.

PMID- 30285978
TI  - Factors Associated With Successful Setup of a Self-Fitting Hearing Aid and the
      Need for Personalized Support.
AB  - OBJECTIVES: Self-fitting hearing aids have the potential to increase the
      accessibility of hearing health care. The aims of this study were to (1) identify
      factors that are associated with the ability to successfully set up a pair of
      commercially available self-fitting hearing aids; 2) identify factors that are
      associated with the need for knowledgeable, personalized support in performing
      the self-fitting procedure; and (3) evaluate performance of the individual steps
      in the self-fitting procedure. DESIGN: Sixty adults with hearing loss between the
      ages of 51 and 85 took part in the study. Half of the participants were current
      users of bilateral hearing aids; the other half had no previous hearing aid
      experience. At the first appointment, participants underwent assessments of
      health locus of control, hearing aid self-efficacy, cognitive status, problem
      solving skills, demographic characteristics, and hearing thresholds. At the
      second appointment, participants followed a set of computer-based instructions
      accompanied by video clips to self-fit the hearing aids. The self-fitting
      procedure required participants to customize the physical fit of the hearing
      aids, insert the hearing aids into the ear, perform self-directed in situ
      audiometry, and adjust the resultant settings according to their preference.
      Participants had access to support with the self-fitting procedure from a trained
      clinical assistant (CA) at all times. RESULTS: Forty-one (68%) of the
      participants achieved a successful self-fitting. Participants who self-fit
      successfully were significantly more likely than those who were unsuccessful to
      have had previous experience with hearing aids and to own a mobile device (when
      controlling for four potential covariates). Of the 41 successful self-fitters, 15
      (37%) performed the procedure independently and 26 (63%) sought support from the
      CA. The successful self-fitters who sought CA support were more likely than those
      who self-fit independently to have a health locus of control that is externally
      oriented toward powerful others. Success rates on the individual steps in the
      self-fitting procedure were relatively high. No one step was more problematic
      than any other, nor was there a systematic tendency for particular participants
      to make more errors than others. Steps that required use of the hearing aids in
      conjunction with the self-fitting app on the participant's mobile device had the
      highest rates of support use. CONCLUSIONS: The findings of this study suggest
      that nonaudiologic factors should be considered when selecting suitable
      candidates for the self-fitting hearing aids evaluated in this study. Although
      computer-based instructions and video clips were shown to improve self-fitting
      skill acquisition relative to past studies in which printed instruction booklets
      were used, the majority of people are still likely to require access to support
      from trained personnel while carrying out the self-fitting procedure, especially
      when this requires the use of an app.

PMID- 30285979
TI  - Pelvic Floor Disorders After Obstetric Avulsion of the Levator Ani Muscle.
AB  - OBJECTIVES: With vaginal childbirth, 10% to 30% of women sustain levator ani
      muscle avulsion. The objective of this study was to estimate the cumulative
      incidence of prolapse and other pelvic floor disorders (PFDs), comparing
      vaginally parous women with and without levator avulsion. METHODS: Parous women
      enrolled in a longitudinal study were assessed annually for PFDs with the Pelvic
      Organ Prolapse Quantification Examination (for prolapse) and the Epidemiology of
      Prolapse and Incontinence Questionnaire (for stress incontinence, overactive
      bladder, and anal incontinence). Three-dimensional transperineal ultrasound was
      used to identify levator avulsion. Women with and without levator avulsion after
      vaginal delivery were compared for the cumulative incidence of PFDs. Further
      analysis also stratified by forceps delivery. RESULTS: At the time of assessment,
      453 participants were 6 to 17 years from first delivery (median, 11 years).
      Levator avulsion was identified in 15% (66/453) and was more common among those
      who had undergone forceps-assisted delivery (P < 0.001). Levator avulsion was
      strongly associated with prolapse beyond the hymen (odds ratio, 2.7; 95%
      confidence interval, 1.3-5.7) and with symptoms of prolapse (odds ratio, 3.0; 95%
      confidence interval-1.2, 7.3). These associations persisted after controlling for
      forceps-assisted delivery. In contrast, the odds of stress incontinence,
      overactive bladder, and anal incontinence were marginally (but not significantly)
      increased among women with levator avulsion in this cohort. CONCLUSIONS:
      Obstetric levator avulsion is strongly associated with pelvic organ prolapse. The
      relationship between levator avulsion and other PFDs may not be significant.

PMID- 30285980
TI  - Implementation of the Smart Use of Antibiotics Program to Reduce Unnecessary
      Antibiotic Use in a Neonatal ICU: A Prospective Interrupted Time-Series Study in
      a Developing Country.
AB  - OBJECTIVES: We aimed to implement our Smart Use of Antibiotics Program to ensure
      the proper use of antimicrobials, improve patient care and outcomes, and reduce
      the risks of adverse effects and antimicrobial resistance. DESIGN: We compared
      the time periods before (baseline) and after (intervention) the implementation of
      an antibiotic protocol by performing surveillance and assessments of all
      antibiotic use during a 29-month interrupted period. SETTING: Level 3-4 neonatal
      ICU in one referral center. PATIENTS: All 13,540 infants who received antibiotics
      during their hospital stay from 2015 to 2017. INTERVENTIONS: Prospective audit of
      targeted antibiotic stewardship program. MEASUREMENTS AND MAIN RESULTS: The
      primary outcome was the change in total antibiotic days of therapy per 1,000
      patient-days between the baseline and intervention periods. The secondary
      outcomes included readmissions for infection, late-onset sepsis (length of stay),
      necrotizing enterocolitis, or death in infants at 32 weeks of gestation or
      younger and the prevalence of multidrug-resistant organism colonization. No
      differences in safety outcomes were observed between the intervention and
      baseline periods. Following the implementation of our Smart Use of Antibiotics
      Program, the total quantity of antibiotics in the intervention phase was
      significantly decreased from 543 days of therapy per 1,000 patient-days to 380
      days of therapy/1,000 patient-days compared with that of baseline (p = 0.0001),
      which occurred in parallel with a reduction in length of stay from 11.4% during
      the baseline period to 6.5% during the intervention period (p = 0.01). A reduced
      multidrug-resistant organism rate was also observed following Smart Use of
      Antibiotics Program implementation (1.4% vs 1.0%; p = 0.02). The overall
      readmission rate did not differ between the two periods (1.2% vs 1.1%; p = 0.16).
      CONCLUSIONS: Smart Use of Antibiotics Program implementation was effective in
      reducing antibiotic exposure without affecting quality of care. Antibiotic
      stewardship programs are attainable through tailoring to special stewardship
      targets even in a developing country.

PMID- 30285981
TI  - Refinement of the Beliefs About Personal Weight Survey.
AB  - This study tested the revised Beliefs About Personal Weight Survey-2 (BPWS-2) in
      200 African American women, 18 to 40 years of age. Confirmatory factor analysis
      of a priori hypothesized factors resulted in 5 subscales-weight acceptance (8
      items); excess weight acknowledgment (5 items); conventional weight regulation (3
      items); circumstantial weight regulation (9 items); and weight concern (10
      items). The Cronbach alpha ranged from 0.67 to 0.89. The factors demonstrated
      patterns of association with eating behavior, body mass index, body image, and
      psychosocial (depression and perceived stress) variables associated with weight.
      The BPWS-2 is the first instrument designed to measure beliefs about one's
      personal weight, thus results make important new contributions to the
      understanding of weight management.

PMID- 30285982
TI  - An Emancipatory Approach to Cultural Competency: The Application of Critical
      Race, Postcolonial, and Intersectionality Theories.
AB  - Nurses teach, work, and conduct research in an increasingly hostile
      sociopolitical climate where health inequities persist among marginalized
      communities. Current approaches to cultural competency do not adequately equip
      nurses to address these complex factors and risk perpetuating stereotypes and
      discrimination. A theory-driven emancipatory approach to cultural competency will
      instead lead to lasting change and uphold the core nursing value of commitment to
      social justice. This article explicates key tenets of critical race, postcolonial
      feminist, and intersectionality theories and then applies them, using an
      emancipatory approach to cultural competency that can reshape nursing education,
      research, and practice.

PMID- 30285983
TI  - Dietary Culture: A Concept Analysis.
AB  - The concept of dietary culture is undefined in the nursing literature. This is
      problematic due to the significant influence of culture on group eating patterns,
      which impact cardiovascular health. Cardiovascular disease is the leading cause
      of death, globally. The purpose of this concept analysis was to define the
      concept of dietary culture to increase the understanding of the relationship
      between diet, culture, and cardiovascular health. Walker and Avant's method was
      employed. This analysis of dietary culture provides insight into the internal
      structure of the concept for future theory development and promotes the
      application of the concept to nursing research and practice.

PMID- 30285984
TI  - Cervical Disk Arthroplasty.
AB  - Anterior cervical diskectomy and fusion has been and remains the benchmark
      surgical management of cervical degenerative disk disease. However, an increased
      use of cervical disk arthroplasty (CDA) has been found in the past few years. The
      purported benefits of CDA included preserved motion, less adjacent-level
      degeneration, and less morbidity. Short-term results from randomized control
      trials clearly showed noninferiority of CDA compared with fusion. With long-term
      comparison data becoming available, results are equivalent and superior in many
      metrics compared, favoring CDA. Concerns remain regarding the best way to manage
      CDA failures. Nonetheless, appropriate patient selection and adherence to strict
      surgical technique make CDA a viable treatment.

PMID- 30285985
TI  - Challenges of Medical Care Delivery in Professional Sports: Lessons From
      Professional Baseball.
AB  - Team medical management for professional sports teams is a demanding and high
      risk activity. Every different sport has unique features and the stresses
      athletes place on themselves, be it from collisions or repetitive stress, result
      in specific challenges for the medical team and team organization in general.
      Injuries in professional sports are costly both to the player and organization.
      The challenges of managing a professional baseball team exemplify these concerns
      and correlate well with other professional sports. Multiple strategies exist for
      improvement of medical care in baseball based on observed deficiencies in player
      evaluation, injury prevention, and injury treatment, which will require
      prospective evaluation to determine their success. These include draft
      strategies, individualized motion and strength analyses, customized in-season and
      off-season training programs for individuals, and standardized treatment
      protocols for injuries all based on best practices. Best practices are currently
      poorly defined in all of these areas.

PMID- 30285986
TI  - Potential Economic Benefits of Limited Clinical and Radiographic Follow-up After
      Plate Fixation of Midshaft Clavicle Fractures.
AB  - INTRODUCTION: The role of routine clinical and radiographic follow-up after
      clavicle fractures are healed was evaluated. METHODS: A retrospective study
      performed in two level-1 trauma centers included 246 adults with healed clavicle
      fractures treated surgically between 2000 and 2013 and at least 24-month follow
      up. Based on radiographs, changes in fracture alignment or implant position from
      union to final follow-up were documented. The average reimbursement for a follow
      up clinical visit and a clavicle radiograph was estimated. RESULTS: Mean time to
      union and mean time of follow-up were of 4.8 and 31.4 months, respectively. No
      changes in implant position or fracture alignment occurred after the fracture had
      healed. The amount reimbursed to our institution for two clinical visits and two
      clavicle radiographs was approximately $300 to $540. CONCLUSION: Once clavicle
      fractures are healed, further radiographic imaging does not provide any notable
      information. Limiting routine follow-up is safe and could be cost-effective for
      the healthcare system. LEVEL OF EVIDENCE: Level-III retrospective cohort study.

PMID- 30285987
TI  - Orthopaedic Resident Use of an Electronic Medical Record Template Does Not
      Improve Documentattion for Pediatric Supracondylar Humerus Fractures.
AB  - INTRODUCTION: Pediatric supracondylar humerus fractures are associated with a
      high incidence of nerve injury. Therefore, it is imperative that documentation be
      complete and accurate. This investigation compares orthopaedic resident history
      and physical (H&P) documentation of pediatric supracondylar fractures for
      completeness and accuracy with and without the use of an electronic medical
      record template. METHODS: The electronic medical record H&P documentation of 119
      supracondylar humerus fractures surgically treated at a single pediatric
      institution was retrospectively reviewed. Templated and nontemplated groups were
      compared for documentation completeness and accuracy. Definitive diagnosis of a
      nerve palsy was made by a supervising orthopaedic attending surgeon. RESULTS:
      Forty-two cases had a templated H&P and 77 did not. The H&P documentation in the
      templated group was markedly more complete than that in the nontemplated group.
      However, the accuracy of the H&P documentation to identify nerve palsy was not
      statistically different between the two groups. Overall, the voluntary use of the
      orthopaedic template declined over time. CONCLUSION: Resident use of an
      orthopaedic template for documenting the H&P of pediatric supracondylar humerus
      fractures compared with nontemplated notes resulted in more complete
      documentation but only comparable accuracy. LEVEL OF EVIDENCE: III.

PMID- 30285988
TI  - Inhospital Complications of Patients With Neuromuscular Disorders Undergoing
      Total Joint Arthroplasty.
AB  - INTRODUCTION: Orthopaedic surgeons are wary of patients with neuromuscular (NM)
      diseases as a result of perceived poor outcomes and lack of data regarding
      complication risks. We determined the prevalence of patients with NM disease
      undergoing total joint arthroplasty (TJA) and characterized its relationship with
      in-hospital complications, prolonged length of stay, and total charges. METHODS:
      Data from the Nationwide Inpatient Sample from 2005 to 2014 was used for this
      retrospective cohort study to identify 8,028,435 discharges with total joint
      arthroplasty. International Classification of Diseases, Ninth Revision, Clinical
      Modification codes were used to identify 91,420 patients who had discharge
      diagnoses for any of the NM disorders of interest: Parkinson disease, multiple
      sclerosis, cerebral palsy, cerebrovascular disease resulting in lower extremity
      paralysis, myotonic dystrophy, myasthenia gravis, myositis (dermatomyositis,
      polymyositis, and inclusion-body myositis), spinal muscular atrophy type III,
      poliomyelitis, spinal cord injury, and amyotrophic lateral sclerosis. Logistic
      regression was used to estimate the association between NM disease and
      perioperative outcomes, including inpatient adverse events, length of stay,
      mortality, and hospital charges adjusted for demographic, hospital, and clinical
      characteristics. RESULTS: NM patients undergoing TJA had increased odds of total
      surgical complications (odds ratio [OR] = 1.21; 95% confidence interval [CI],
      1.17 to 1.25; P < 0.0001), medical complications (OR = 1.41; 95% CI, 1.36 to
      1.46; P < 0.0001), and overall complications (OR = 1.32; 95% CI, 1.28 to 1.36; P
      < 0.0001) compared with non-NM patients. Specifically, NM patients had increased
      odds of prosthetic complications (OR = 1.09; 95% CI, 0.84 to 1.42; P = 0.003),
      wound dehiscence (OR = 5.00; 95% CI, 1.57 to 15.94; P = 0.0002), acute
      postoperative anemia (OR = 1.20; 95% CI, 1.16 to 1.24; P < 0.0001), altered
      mental status (OR = 2.59; 95% CI, 2.24 to 2.99; P < 0.0001), urinary tract
      infection (OR = 1.45; 95% CI, 1.34 to 1.56; P < 0.0001), and deep vein thrombosis
      (OR = 1.27; 95% CI, 1.02 to 1.58; P = 0.021). No difference of in-hospital
      mortality was observed (P = 0.155). DISCUSSION: Because more patients with NM
      disease become candidates of TJA, a team of neurologists, anesthesiologists,
      therapists, and orthopaedic surgeon is required to anticipate, prevent, and
      manage potential complications identified in this study. LEVEL OF EVIDENCE: Level
      III, retrospective cohort study.

PMID- 30285989
TI  - Free Latissimus Dorsi Myocutaneous Flap in a 6-Month-Old Child for Reconstruction
      of a Temporal Fossa Defect After Teratoma Resection.
AB  - Although free flap reconstruction has already gained widespread acceptance in
      pediatric patients, little is known about the outcome of free tissue transfer in
      head and neck reconstruction in pediatric patients. We present a case of a 6
      month-old boy with a large volume deficit in the right temporal fossa after
      resection of a teratoma. This led to a large volume deficit with widely
      undermined skin margins. Therefore, we provided volume augmentation by
      microsurgical free latissimus dorsi myocutaneous flap transplantation.
      Intraoperative use of laser-assisted indocyanine green angiography indicated
      excellent flap perfusion. Postoperative magnetic resonance imaging showed
      adequate flap perfusion with no signs of flap necrosis. To our best knowledge,
      this case presents the youngest patient who underwent free flap transplantation
      in the head and neck region. Our case demonstrates that microvascular surgery can
      play an important role in particular cases in pediatric oncology, even in very
      young patients.

PMID- 30285990
TI  - Unfiltered Nanofat Injections Rejuvenate Postburn Scars of Face.
AB  - The aim of this study was to compare the quality of postburn facial scars before
      and after injection of unfiltered nanofat. The study was performed in the Plastic
      Surgery Department of Mayo Hospital, Lahore, Pakistan, from January 2015 to
      December 2016. Forty-eight patients with postburn facial scars were included; age
      range was 4 to 32 years with Fitzpatrick skin types between 3 and 4. Patients
      with hypertrophic scars, contractures, or keloids were excluded. Scars were
      assessed by a senior plastic surgeon and the patient on the POSAS (Patient
      Observer Scar Assessment Scale). Fat was harvested from the abdomen and/or thighs
      with a 3-mm multiport liposuction cannula (containing several sharp side holes of
      1 mm) using Coleman technique. The harvested fat was emulsified and transferred
      into 1-mL Luer-Lock syringes for injection into the subdermal or intradermal
      plane. Final follow-up was scheduled at 6 months, and scar was rated by the
      patient and the same surgeon on the POSAS. Preoperative and postoperative scar
      scores were compared, and P values were calculated. Results indicated that after
      nanofat grafting, there was a statistically significant improvement in scar
      quality. The most significant improvements on the observer scale were seen in
      pigmentation and pliability (P < 0.0001). Thickness and relief were the least
      improved variables (P = of 0.785 and 0.99, respectively). ImageJ scanning also
      showed pigmentation change (P = 0.076). A statistically significant improvement
      was seen in all parameters of the patient section of the POSAS (P < 0.0001). In
      conclusion, unfiltered nanofat grafting seems to be a promising and effective
      therapeutic approach in postburn facial scars, showing significant improvement in
      scar quality. The trial was registered on www.clinicaltrials.gov with following
      ID NCT03352297.

PMID- 30285991
TI  - Temporary Ectopic Implantation of an Amputated Leg Using the Distal Runoff Vessel
      of the Anterolateral Thigh Flap Followed by Subsequent Prefabricated Chimeric
      Replantation.
AB  - AIM: Infrapopliteal replantation is indicated in selected patients. When the
      patient is hemodynamically unstable or the amputation site is severely
      contaminated, temporary ectopic implantation of the amputated limb is an option.
      To the best of our knowledge, this is the first case report using the distal
      runoff vessel of the anterolateral thigh flap for temporary ectopic implantation
      of an amputated leg followed by replantation with the prefabricated anterolateral
      thigh flap. PATIENT AND METHODS: A 28-year-old male driver had left leg avulsion
      amputation after a car accident. Because of concerns about the high-energy trauma
      mechanism and extensive trauma zone, temporary ectopic implantation was planned
      to avoid a lengthy replantation procedure and to enable future replantation. The
      amputated leg was implanted to the thigh using the distal runoff vessel of the
      descending branch of the lateral circumflex femoral system in the preservation of
      proximal cutaneous perforator. When the patient became hemodynamically stable and
      the amputated stump was relatively clean and healthy, we replanted the amputated
      leg with the prefabricated anterolateral thigh flap on day 7. RESULTS: The
      replanted leg and anterolateral thigh flap survived well after the procedure. At
      the 15-month follow-up, the patient could walk independently. There was no need
      for custom-made shoes because there was no obvious leg length discrepancy and the
      flap was not bulky. CONCLUSIONS: We believe that the distal runoff vessel of the
      descending branch of the lateral circumflex femoral system can not only serve as
      a recipient site for temporary ectopic implantation but also enable the harvest
      of a prefabricated anterolateral thigh flap with the amputated part at the
      replantation stage. This prefabricated tissue containing the anterolateral thigh
      flap and the amputated part needs only 1 set of vascular anastomosis to
      accomplish replantation and simultaneous revascularization of the anterolateral
      thigh flap. Most importantly, this ectopically prefabricated chimeric tissue
      minimizes the need for extensive bone shortening after radial debridement by
      providing sufficient soft tissue coverage at the replantation stage.

PMID- 30285992
TI  - Alteration of Sciatic Nerve Histology and Electrical Function After Compression
      and After Neurolysis in a Diabetic Rat Model.
AB  - BACKGROUND: Diabetic rats are more sensitive to nerve entrapment. This study was
      conducted to evaluate nerve function and histological changes in diabetic rats
      after nerve compression and subsequent decompression. METHODS: A total of 35
      Wistar rats were included. The experimental group was divided into diabetic
      sciatic nerve compression group (DSNC, n = 5) and diabetic sciatic nerve
      decompression group (DSND, n = 20). The DSNC model was created by wrapping a
      silicone tube circumferentially around the nerve for 4 weeks, and then the DSND
      group accepted nerve decompression and was followed up to 12 weeks. The DSND
      group was equally divided into DSND 3 weeks (DSND3), 6 weeks (DSND6), 9 weeks
      (DSND9), and 12 weeks (DSND12) groups. Five rats were taken as normoglycemic
      control group (CR, n = 5), and another 5 rats as diabetic control group (DM, n =
      5). The mechanical hyperalgesia of rats was detected by Semmes-Weinstein nylon
      monofilaments (SWMs) and by motor nerve conduction velocity (MNCV). These 2
      physiological indicators and histology of sciatic nerves were compared among
      different groups. RESULTS: The SWM measurements improved toward normal values
      after decompression. The SWM value was significantly lower (more normal) in the
      DSNC groups than in the DSND group (P < 0.05). The MNCV was 53.7 +/- 0.8 m/s in
      the CR group, whereas it was 28.4 +/- 1.0 m/s in the DSNC group (P < 0.001). Six
      weeks after decompression, the MNCV was significantly faster than that in the
      DSNC group (P < 0.001). Histological examination demonstrated chronic nerve
      compression, which responded toward normal after decompression, but with degree
      of myelination never recovering to normal. CONCLUSIONS: Chronic compression of
      the diabetic sciatic nerve has measureable negative effects on sciatic nerve
      motor nerve function, associated with a decline of touch/pressure threshold and
      degeneration of myelin sheath and axon. Nerve decompression surgery can reverse
      these effects and partially restore nerve function.

PMID- 30285993
TI  - A New Method for Double-Eyelid Blepharoplasty Using Orbital Septum.
AB  - BACKGROUND: This article presents a new method using orbital septum for double
      eyelid blepharoplasty. METHODS: During double-eyelid blepharoplasty, we incised
      the orbital septum horizontally. Using the attachment site of the levator
      aponeurosis as a pedicle, the lower part of the dissected orbital septum was
      turned downward and then sutured to the upper border of the lower orbicularis
      oculi muscle and posterior pretarsal fascia. We evaluated the efficacy of this
      double-eyelid surgical procedure in patients undergoing the procedure from
      December 2015 to October 2017. RESULTS: We included 462 eyes of 231 patients in
      the final analysis. Sutures were removed 7 days after surgery. All double-eyelid
      creases were well formed, and the eyelids closed well. Six-month follow-up
      results revealed that the double-eyelid shape was natural looking, and no
      patients experienced upper eyelid retraction or incomplete eye closure. Notched
      scars did not occur, and patient satisfaction was achieved in all cases. Two
      hundred eleven patients were fully satisfied with the surgical results, and 20
      were basically satisfied with the surgical results. CONCLUSIONS: Using the
      orbital septum is a good approach for double-eyelid blepharoplasty.

PMID- 30285994
TI  - Occlusion, Occlusion, Where Art Thou?

PMID- 30285996
TI  - "Atrophic Kidney"-like Lesion: Clinicopathologic Series of 8 Cases Supporting a
      Benign Entity Distinct From Thyroid-like Follicular Carcinoma.
AB  - Renal mass lesions with a follicular architecture resembling atrophic kidney have
      been described, but their distinction from thyroid-like follicular carcinoma of
      the kidney remains controversial. We collected 8 cases of this purported
      "atrophic kidney"-like lesion to fully describe their clinical and histologic
      spectrum, their possible etiology, and to discuss their distinction from other
      renal neoplasms. Eight total cases were identified with patient ages ranging from
      9 to 48 years (mean: 29 y; median: 28.5 y). Four patients were female and 4 were
      male. The tumors were unifocal and size ranged from 1.6 to 4.9 cm (mean: 3.4 cm;
      median: 3.4 cm). All 8 tumors had a remarkably similar histology. Each was
      enveloped by a smooth muscle rich capsule and had an overall low power
      "follicular" architecture. The luminal spaces of the "follicles" (or cysts)
      contained eosinophilic secretions and the lining epithelium was often flattened
      and atrophic, but some had more rounded cells with a distinctive hobnail
      arrangement. Many cysts contained discohesive round cells floating within the
      eosinophilic material, and some contained small intraluminal tufts with features
      of markedly atrophic glomeruli. Periodic acid-Schiff stains highlighted basement
      membrane material extending into these glomerular-like tufts, and some contained
      small distinct capillaries surrounded by endothelial cells, interspersed
      mesangial-like cells, and rare surrounding podocyte-like cells, providing
      additional evidence for glomerulocystic structures. Scattered calcifications were
      present within cysts (or within cyst walls) in varying numbers and were
      characterized by 2 types: psammoma body-like or more amorphous deposits. The
      tissue between cystic glomeruli contained predominantly small atrophic tubular
      structures, but collagenized stroma and smaller collapsed glomeruli were also
      present. The 2 tumors from the oldest 2 patients (48 and 39 y) had a more
      striking degree of stromal hyalinization. Immunohistochemically, the cyst lining
      cells had a predominant WT-positive/PAX-8 negative/CK7-negative phenotype, while
      tubules were typically WT-1 negative/PAX-8 positive/CK7-positive. Upon comparison
      to a control group of 10 kidneys containing incidental non-mass-forming
      glomerulocystic change, the morphologic features and immunophenotype were
      identical. To date, no patient has had any recurrence or aggressive clinical
      behavior based on follow status in 7 of 8 cases (follow-up range: 9 to 168 mo;
      median: 24 mo; mean: 40 mo). In summary, we describe the clinicopathologic
      features of 8 unique, benign "atrophic kidney"-like lesions that may simply
      represent a non-neoplastic form of organizing tubular atrophy and glomerulocystic
      change, and emphasize their distinction from thyroid-like follicular carcinoma of
      the kidney.

PMID- 30285995
TI  - VSTM2A Overexpression Is a Sensitive and Specific Biomarker for Mucinous Tubular
      and Spindle Cell Carcinoma (MTSCC) of the Kidney.
AB  - Our recent study revealed recurrent chromosomal losses and somatic mutations of
      genes in the Hippo pathway in mucinous tubular and spindle cell carcinoma
      (MTSCC). Here, we performed an integrative analysis of 907 renal cell carcinoma
      (RCC) samples (combined from The Cancer Genome Atlas and in-house studies) and
      the Knepper data set of microdissected rat nephrons. We identified VSTM2A and
      IRX5 as novel cancer-specific and lineage-specific biomarkers in MTSCC. We then
      assessed their expression by RNA in situ hybridization (ISH) in 113 tumors,
      including 33 MTSCC, 40 type 1 papillary RCC, 8 type 2 papillary RCC, 2
      unclassified RCC, 15 clear cell RCC, and 15 chromophobe RCC. Sensitivity and
      specificity were calculated as the area under the receiver operating
      characteristics curve (AUC). All MTSCC tumors demonstrated moderate to high
      expression of VSTM2A (mean ISH score=255). VSTM2A gene expression assessed by RNA
      sequencing strongly correlated with VSTM2A ISH score (r=0.81, P=0.00016). The
      majority of non-MTSCC tumors demonstrated negative or low expression of VSTM2A.
      IRX5, nominated as a lineage-specific biomarker, showed moderate to high
      expression in MTSCC tumors (mean ISH score=140). IRX5 gene expression assessed by
      RNA sequencing strongly correlated with IRX5 ISH score (r=0.69, P=0.00291).
      VSTM2A (AUC: 99.2%) demonstrated better diagnostic efficacy than IRX5 (AUC:
      87.5%), and may thus serve as a potential diagnostic marker to distinguish tumors
      with overlapping histology. Furthermore, our results suggest MTSCC displays an
      overlapping phenotypic expression pattern with the loop of Henle region of normal
      nephrons.

PMID- 30285997
TI  - Adamantinoma-like Ewing Sarcoma of the Salivary Glands: A Newly Recognized
      Mimicker of Basaloid Salivary Carcinomas.
AB  - Adamantinoma-like Ewing sarcoma (ALES) is a rare tumor that demonstrates the
      EWSR1-FLI1 translocation characteristic of Ewing sarcoma despite overt epithelial
      differentiation including diffuse expression of cytokeratins and p40. Most cases
      of ALES described to date have occurred in the head and neck where they can mimic
      a wide range of small round blue cell tumors. Because distinguishing ALES from
      basaloid salivary gland carcinomas can be particularly difficult, we analyzed a
      series of 10 ALESs that occurred in the salivary glands with the aim of
      identifying features that allow for better recognition of this entity. The
      salivary ALESs included 8 parotid gland and 2 submandibular gland tumors in
      patients ranging from 32 to 77 years (mean: 52 y). Nine were initially
      misclassified as various epithelial neoplasms. Although these tumors displayed
      the basaloid cytology, rosette formation, infiltrative growth, and nuclear
      monotony characteristic of ALES, peripheral palisading and overt keratinization
      were relatively rare in this site. Salivary ALESs not only displayed positivity
      for AE1/AE3, p40, and CD99, but also demonstrated a higher proportion of
      synaptophysin reactivity than has been reported for nonsalivary ALESs. These
      morphologic and immunohistochemical findings make ALES susceptible to
      misclassification as various other tumors including basal cell adenocarcinoma,
      adenoid cystic carcinoma, squamous cell carcinoma, NUT carcinoma, large cell
      neuroendocrine carcinoma and myoepithelial carcinoma. Nevertheless, monotonous
      cytology despite highly infiltrative growth and concomitant positivity for p40
      and synaptophysin can provide important clues for consideration of ALES, and
      identification of the defining EWSR1-FLI1 translocations can confirm the
      diagnosis.

PMID- 30285998
TI  - Eleven Years of Clozapine Experience in Autism Spectrum Disorder: Efficacy and
      Tolerance.
AB  - BACKGROUND: Autism spectrum disorders (ASDs) are neurodevelopmental disorders
      that comprise wide graduated clinical expressions but similar core symptoms
      (repetitive, stereotyped behavior, and social communication disabilities). Many
      patients with ASD have disruptive behaviors like aggressiveness, temper tantrums,
      or self-injury that interfere with their socializations, their learning
      abilities, and their quality of life. These behaviors represent a common target
      for pharmacology. Beherec et al (J Clin Psychopharmacol. 2011;31:341-344) (first
      cohort), showed the efficacy of clozapine on disruptive behaviors in 6 patients
      with autism who were older than 16 years. The aim of this study was to assess the
      efficacy and tolerance of clozapine in a new cohort and the long-term effect in
      our first cohort. PROCEDURES: Concerning the replication study, we conducted a
      retrospective study of the changes of aggressive behaviors for all patients with
      ASD who were treated with clozapine from 2011 to 2017. Disruptive behaviors were
      monitored from 1 to 6 months before and after the initiation of the clozapine.
      RESULTS: All the patients of the first cohort were still on clozapine after an
      average of 11 + 2.6 years, with the same efficacy and no serious adverse effect
      was noted. For the replication study, 13 patients were included. Clozapine
      resulted in a significant decrease in the number of the days with aggression
      (65.2% + 32.6%). Once again, no serious adverse effect was notified. All the
      patients had a better quality of life. CONCLUSIONS: Our study confirms that
      clozapine could be an efficacious and well-tolerated treatment for ASD patients
      with disruptive behaviors who do not respond to other antipsychotics on the long
      term.

PMID- 30285999
TI  - Withdrawal-Emergent Dyskinesia After Acute Discontinuation of Risperidone in a
      Child With Autism Spectrum Disorder.

PMID- 30286000
TI  - Antisense Oligonucleotides in Psychiatric Disorders.

PMID- 30286001
TI  - Anatomy of the Superficial Venous Structures of the Neck: A Cadaveric Study to
      Guide Superficial Injections.
AB  - BACKGROUND: Minimally invasive aesthetic procedures of the neck are becoming more
      popular. However, anatomical studies on the venous structures of the neck in
      relation to these procedures are lacking. OBJECTIVE: The aims of this study were
      to identify the locations and communication patterns of the anterior jugular vein
      and external jugular vein (AJV and EJV) and the communicating vein (CV) based on
      superficial anatomical landmarks and to determine dangerous areas for dermal
      filler injections into the neck. MATERIALS AND METHODS: Thirty sides of the neck
      from Korean adult cadavers were dissected for this study. RESULTS: Four
      anatomical variants were identified. In Type Ia, the CV ran along the anterior
      border of the sternocleidomastoid muscle (SCM) (33.4%); in Type Ib, a single vein
      was observed connecting the CV and the EJV at the level of laryngeal prominence
      (23.3%); in Type Ic, the CV proceeded separately from the medial side of the
      anterior border of the SCM (13.3%); and in Type II, the CV was absent while the
      EJV and AJV were observed (30%). CONCLUSION: Given the 4 anatomical variants
      identified in this study, the authors recommend exerting caution when performing
      dermal filler injections approximately 10, 30, and 60 mm lateral to the
      midsagittal line to avoid iatrogenic side effects.

PMID- 30286002
TI  - Letter to the Editor: Five Hundred Fifty-five Retrieved Metal-on-metal Hip
      Replacements of a Single Design Show a Wide Range of Wear, Surface Features, and
      Histopathologic Reactions.

PMID- 30286003
TI  - Predicting the Depth of the Lumbar Plexus in Pediatric Patients: A Retrospective
      Magnetic Resonance Imaging Study.
AB  - BACKGROUND: The lumbar plexus (LP) block is commonly used for analgesia for lower
      extremities. If the depth of the LP (LPD) can be predicted, the performance time
      and procedure-related complications could be reduced. METHODS: Three hundred
      sixty-one magnetic resonance images of pediatric patients (<18 years of age) were
      analyzed. Simple linear regression and multiple linear regression analyses were
      performed to predict the LPD using patient age, weight, height, and the distance
      between the midline and posterior superior iliac spine (midline-PSIS). The ratio
      of the distance between the midline and the most lateral aspect of the LP
      (midline-LP) to midline-PSIS (midline-LP/midline-PSIS ratio) was calculated to
      suggest a needle insertion point at the L4/L5 intervertebral level. The presence
      of the kidney at the L4 level and the L4/L5 intervertebral level was determined.
      RESULTS: The LPD at the L4/L5 intervertebral levels was predicted using the
      equation LPD = 0.844 * weight (kg) + 25.8 (mm) in pediatric patients <18 years of
      age (r = 0.791; 95% confidence interval [CI] of r, 0.753-0.829). The overall
      midline-LP/midline-PSIS ratio was 0.87 (95% CI, 0.86-0.89), and the ratio was
      higher in neonates and infants (0.98 [95% CI, 0.95-1.02]) than in the other age
      groups. The presence of the lower kidney pole at the L4 level was common in
      pediatric patients (43.7% of neonates and infants and 13.7% of toddlers and
      preschool-aged children). The lower kidney pole was observed at the L4/L5 level
      in 6 patients (1.7%). CONCLUSIONS: When LP block is performed in pediatric
      patients, the LPD and risk of renal injury should be considered for successful
      and safe analgesic block.

PMID- 30286004
TI  - Predicting the Size of a Left Double-Lumen Tube for Asian Women Based on the
      Combination of the Diameters of the Cricoid Ring and Left Main Bronchus: A
      Randomized, Prospective, Controlled Trial.
AB  - BACKGROUND: There are limited data about how to choose the correct size of a
      double-lumen tube (DLT). It is especially difficult to select an appropriate DLT
      for Asian women because of their small stature. The primary aim of this study was
      to compare the overall accuracy of the DLT selected based on the combination of
      transverse diameter of cricoid ring and the equivalent diameter of the left main
      bronchus (ED-LMB) with that based on the ED-LMB alone for Asian women. METHODS:
      In this study, 80 consecutive and blinded female patients were assigned randomly
      to 2 groups. The overall accuracy of the selection of DLT was compared between
      the Combined group and LMB group. The accuracy of the selection of tracheal
      segment and bronchial segment was also compared between the 2 groups. The
      postoperative hoarseness and sore throat were investigated by blinded assessors.
      RESULTS: The overall accuracy of selection of the DLTs was higher in the Combined
      group than that in the LMB group (87.5% vs 60.0%; P = .010). The accuracy of
      selection of tracheal segment was also higher in the Combined group (92.5% vs
      67.5%; P = .010). The accuracy of selection of bronchial segment was similar
      between the groups (95.0 % vs 86.1%; P = .246). The severity of sore throat was
      higher in the LMB group at 24 hours after the operation (P = .001). CONCLUSIONS:
      The correct size of DLT for Asian women should be selected based on the
      combination of transverse diameter of cricoid ring and the ED-LMB.

PMID- 30286005
TI  - Regional Anesthesia and Readmission Rates After Total Knee Arthroplasty.
AB  - BACKGROUND: Total knee arthroplasty is a commonly performed procedure and an
      important contributor to national health care spending. Reducing the incidence of
      readmission could have important consequences for patient well-being and relevant
      financial implications. Whether regional anesthesia techniques are associated
      with decreased readmission rates and costs among privately insured patients
      remains unknown. METHODS: Using administrative claims data, we identified 138,362
      privately insured patients 18-64 years of age who underwent total knee
      arthroplasty between 2002 and 2013. We then examined whether the use of a nerve
      block was associated with decreases in readmission rates and related costs during
      the 90 days after discharge. Our analyses were adjusted for potential confounding
      variables including medical comorbidities and previous use of opioids and other
      medications. RESULTS: After adjusting for patient demographics, comorbidities,
      and preoperative medication use, the adjusted 90-day readmission rate was 1.8%
      (95% confidence interval [CI], 1.1-2.4) among patients who did not receive a
      block compared to 1.7% (95% CI, 1.1-2.4) among patients who did (odds ratio,
      0.99; 95% CI, 0.91-1.09; P = .85). The adjusted readmission-related postoperative
      cost for patients who did not receive a block was $561 (95% CI, 502-619) and $574
      (95% CI, 508-639) for patients who did (difference, $13; 95% CI, -75 to 102; P =
      .74). This lack of statistically significant differences held for subgroup and
      sensitivity analyses. CONCLUSIONS: Nerve blocks were not associated with improved
      measures of long-term postoperative resource use in this younger, privately
      insured study population.

PMID- 30286006
TI  - Predosing Chemical Stability of Admixtures of Propofol, Ketamine, Fentanyl, and
      Remifentanil.
AB  - Admixtures of propofol-ketamine, propofol-ketamine-fentanyl, and propofol
      ketamine-remifentanil were subjected to various clinically relevant conditions to
      study their chemical stability. A novel high-performance liquid chromatography
      mass spectrometry method revealed no degradation of any compound by incubation at
      37 degrees C, constant mixing, or table-top storage for 6- and 24-hour time
      periods, except variable recovery of both propofol and fentanyl in the admixtures
      of propofol-ketamine-fentanyl suggesting possible degradation.

PMID- 30286007
TI  - Resident Competency and Proficiency in Combined Spinal-Epidural Catheter
      Placement Is Improved Using a Computer-Enhanced Visual Learning Program: A
      Randomized Controlled Trial.
AB  - BACKGROUND: Physician educators must balance the need for resident procedural
      education with clinical time pressures as well as patient safety and comfort.
      Alternative educational strategies, including e-learning tools, may be beneficial
      to orient novice learners to new procedures and speed proficiency. We created an
      e-learning tool (computer-enhanced visual learning [CEVL] neuraxial) to enhance
      trainee proficiency in combined spinal-epidural catheter placement in obstetric
      patients and performed a randomized controlled 2-center trial to test the
      hypothesis that use of the tool improved the initial procedure performed by the
      anesthesiology residents. METHODS: Anesthesiology residents completing their
      first obstetric anesthesiology rotation were randomized to receive online access
      to the neuraxial module (CEVL group) or no access (control) 2 weeks before the
      rotation. On the first day of the rotation, residents completed a neuraxial
      procedure self-confidence scale and an open-ended medical knowledge test. Blinded
      raters observed residents performing combined spinal-epidural catheter techniques
      in laboring parturients using a procedural checklist (0-49 pts); the time
      required to perform the procedure was recorded. The primary outcome was the
      duration of the procedure. RESULTS: The CEVL group had significantly shorter mean
      (+/-standard deviation) procedure time compared to the control group 22.5 +/- 4.9
      vs 39.5 +/- 7.1 minutes (P < .001) and had higher scores on the overall
      performance checklist 36.4 +/- 6.6 vs 28.8 +/- 7.1 (P = .012). The intervention
      group also had higher scores on the open-ended medical knowledge test (27.83 +/-
      3.07 vs 22.25 +/- 4.67; P = .002), but self-confidence scores were not different
      between groups (P = .64). CONCLUSIONS: CEVL neuraxial is a novel prerotation
      teaching tool that may enhance the traditional initial teaching of combined
      spinal-epidural procedures in obstetric anesthesiology. Future research should
      examine whether the use of web-based learning tools impacts long-term provider
      performance or patient outcomes.

PMID- 30286008
TI  - Red Blood Cell Transfusion in Pediatric Orthotopic Liver Transplantation: What a
      Difference a Few Decades Make.
AB  - BACKGROUND: Liver transplantation in children is often associated with
      coagulopathy and significant blood loss. Available data are limited. In this
      observational retrospective study, we assessed transfusion practices in pediatric
      patients undergoing liver transplantation at a single institution over the course
      of 9 years. METHODS: Data were retrospectively collected from patient medical
      records at the Children's Hospital of Pittsburgh of University of Pittsburgh
      Medical Center. All patients who underwent liver transplantation from January
      2008 to June 2017 were included. Primary and secondary outcomes were volume of
      red blood cells (RBCs) transfused and mortality, respectively. RESULTS: From
      January 2008 to June 2017, there were 278 liver transplants in 271 patients. The
      number of primary transplants were 259, second retransplants 15, and third
      retransplants 4. Average age at transplantation was 6.9 years. Biliary atresia,
      maple syrup urine disease, urea cycle defect, and liver tumor were the leading
      indications accounting for 66 (23.7%), 45 (16.2%), 24 (8.6%), and 23 (8.3%) of
      transplants, respectively. Seventy-six cases (27.3%) did not require RBC
      transfusions. Among those transfused, 181 (89.6%) of the cases required <1 blood
      volume (BV). The median BV transfused among all cases was 0.21 (range, 0-9; Q1,
      0; Q3, 0.45). There is a trend toward higher volume transfusions among infants
      (median, 0.46 BV) compared to children >12 months of age (0.12 BV). By diagnosis,
      the group requiring the highest median volume transfusion was patients with total
      parenteral nutrition-related liver failure (3.41 BV) followed by patients
      undergoing repeat transplants (0.6 BV). Comparison of primary versus repeat
      transplants shows a trend toward higher volume transfusions in third transplants
      (median, 2.71 BV), compared to second transplants (0.43 BV) and primary
      transplants (0.18 BV). Four of 271 patients (1.5%) died during admission
      involving liver transplantation. Nine of 271 patients (3.3%) died subsequently.
      Total mortality was 4.8%. CONCLUSIONS: In contrast to historically reported
      trends, evaluation of current transfusion practices reveals that most patients
      undergoing liver transplantation receive <1 BV of packed RBCs. More than 1 in 4
      transplantations require no transfusion at all. Risk factors for greater
      transfusion need include younger age, total parenteral nutrition-related liver
      failure, and repeat transplantation.

PMID- 30286009
TI  - Real-Time Measurement of Xenon Concentration in a Binary Gas Mixture Using a
      Modified Ultrasonic Time-of-Flight Anesthesia Gas Flowmeter: A Technical
      Feasibility Study.
AB  - BACKGROUND: Xenon (Xe) is an anesthetic gas licensed for use in some countries.
      Fractional concentrations (%) of gases in a Xe:oxygen (O2) mixture are typically
      measured using a thermal conductivity meter and fuel cell, respectively. Speed of
      sound in such a binary gas mixture is related to fractional concentration,
      temperature, pressure, and molar masses of the component gases. We therefore
      performed a study to assess the feasibility of developing a novel single
      sterilizable device that uses ultrasound time-of-flight to measure both real-time
      flowmetry and fractional gas concentration of Xe in O2. METHODS: For the purposes
      of the feasibility study, we adapted an ultrasonic time-of-flight flowmeter from
      a conventional anesthetic machine to additionally measure real-time fractional
      concentration of Xe in O2. A total of 5095 readings of Xe % were taken in the
      range 5%-95%, and compared with simultaneous measurements from the gold standard
      of a commercially available thermal conductivity Xe analyzer. RESULTS: Ultrasonic
      measurements of Xe (%) showed agreement with thermal conductivity meter
      measurements, but there was marked discontinuity in the middle of the measurement
      range. Bland-Altman analysis (95% confidence interval in parentheses) yielded:
      mean difference (bias) 3.1% (2.9%-3.2%); lower 95% limit of agreement -4.6% (
      4.8% to -4.4%); and upper 95% limit of agreement 10.8% (10.5%-11.0%).
      CONCLUSIONS: The adapted ultrasonic flowmeter estimated Xe (%), but the level of
      accuracy is insufficient for clinical use. With further work, it may be possible
      to develop a device to perform both flowmetry and binary gas concentration
      measurement to a clinically acceptable degree of accuracy.

PMID- 30286010
TI  - Prior History of Pancreatitis Accelerates the Development of Pancreatic
      Adenocarcinoma.
AB  - OBJECTIVES: Presentation of pancreatic adenocarcinoma (PC) as acute pancreatitis
      (AP), association of chronic pancreatitis (CP) with PC, and role of inflammation
      in PC carcinogenesis are well recognized. We hypothesized that inflammatory
      changes associated with remote history of AP (>=2 years before PC diagnosis)
      would result in earlier age of PC diagnosis. METHODS: We evaluated PC patients
      prospectively enrolled in the Pancreatic Adenocarcinoma Gene Environment Risk
      (PAGER) study at the University of Pittsburgh for history of pancreatitis and
      reviewed relevant medical records and imaging studies. Univariate and
      multivariable linear regression analyses evaluated the relationship between PC
      and remote history of AP. RESULTS: Among 790 patients with histologically
      confirmed PC, 114 (14.4%) had a history of pancreatitis (AP within 2 years of PC
      diagnosis in 69 [8.7%], remote history of AP in 28 [3.5%], CP in 4 [0.5%], and
      unknown duration of pancreatitis in 13 [1.6%]). After controlling for age, sex,
      body mass index, smoking, alcohol history, and diabetic status at diagnosis,
      patients with a remote history of AP were diagnosed on average 4.7 years earlier
      with PC when compared with PC patients without history of AP (P < 0.035).
      CONCLUSIONS: Remote history of AP may accelerate carcinogenesis in PC.

PMID- 30286011
TI  - Prognostic Impact of Portal System Invasion in Pancreatic Cancer Based on Image
      Classification.
AB  - OBJECTIVES: This study aimed to clarify the correlation between image
      classification and the pathological degree of portal system invasion (PSI) and to
      evaluate the prognostic impact of PSI in pancreatic cancer (PC). METHODS:
      Pancreatic cancer patients with surgical resections (head, n = 244; body and
      tail, n = 80) were enrolled in this study. RESULTS: Based on imaging findings,
      portal vein (PV) invasion was classified as type A (absent), B (unilateral
      narrowing), C (bilateral narrowing), or D (stenosis or obstruction with
      collaterals). Splenic vein (SPV) invasion was classified as type alpha (absent),
      beta (stenosis), or gamma (obstruction). The pathological grade of venous
      invasion was classified as grade 0 (no invasion), 1 (tunica adventitia), 2
      (tunica media), or 3 (tunica intima). In PV and SPV invasions, image
      classification and pathological grade showed significant correlation (PV: rho =
      0.696; SPV: rho = 0.681). Patients with PV invasion deeper than type B exhibited
      significantly poorer survival than type A (P < 0.0001). In contrast, there was no
      difference in survival among types alpha, beta, and gamma. CONCLUSIONS: Image
      classification was correlated with the pathological grade of PSI in PC. Although
      not applicable for SPV invasion, image classification of PV invasion is a robust
      indicator for PC prognosis.

PMID- 30286012
TI  - Evaluation of Pancreatic Fibrosis With Acoustic Radiation Force Impulse Imaging
      and Automated Quantification of Pancreatic Tissue Components.
AB  - OBJECTIVES: The aim of this study was to determine whether computer-assisted
      digital analysis and acoustic radiation force impulse (ARFI) imaging were useful
      for assessing pancreatic fibrosis, and if ARFI imaging predicted postoperative
      pancreatic fistula (POPF). METHODS: Seventy-eight patients scheduled to undergo
      pancreatic resection were enrolled. Shear wave velocity (SWV) at the pancreatic
      neck was measured preoperatively using ARFI imaging. Pancreatic tissue components
      on a whole slide image were quantified using an automatic image processing
      software. The relationship between SWV, fibrotic tissue content, and POPF
      incidence and clinical severity was analyzed. RESULTS: The median collagen fiber,
      fatty tissue, and acinar cell contents were 11.6%, 8.5%, and 61.3%, respectively.
      Unlike fatty tissue, collagen fiber content and acinar cells were correlated with
      SWV (rho = 0.440, P < 0.001 and rho = -0.428, P < 0.001, respectively). Although
      collagen fiber content and SWV were associated with the overall incidence of POPF
      (P = 0.004 and 0.001, respectively), collagen fiber content and SWV had no
      statistical correlation with clinically relevant POPF (P = 0.268 and 0.052,
      respectively). CONCLUSIONS: We objectively quantified the pancreatic tissue
      components using an automatic image processing software. Shear wave velocity was
      significantly related to collagen fiber content and suggests that ARFI imaging
      can be useful for evaluating pancreatic fibrosis.

PMID- 30286013
TI  - Understanding Pancreatic Diseases Using Animated Pancreas Patient: Informing
      Patients for Better Health Outcomes With Visual Formats of Learning.
AB  - OBJECTIVES: The aim of this study was to evaluate the impact of Animated Pancreas
      Patient (APP) educational modules (APP website and YouTube) on pancreas
      education, awareness, and health outcomes. METHODS: This was a retrospective
      study of APP metrics data from September 2013 to October 2017. We evaluated
      audience reach (number of visit sessions, unique visitors, page views) and
      calculated top views by media type (animation, expert video, patient video, and
      slide show) and top retention videos from the modules. We also assessed the
      educational impact through learner feedback survey. RESULTS: The APP had
      1,475,252 views (547,693 unique visitors, 63.1% in United States) during the
      study period. Most popular topic viewed among the animations was "Role and
      Anatomy of the Pancreas" (n = 361,116), and most common expert video viewed was
      "Chronic Pancreatitis: What Foods and Beverages Should I Avoid?" (n = 31,667).
      Participants who completed the online feedback survey reported knowledge gains
      and commitments to change. CONCLUSIONS: Pancreas education in visual formats of
      learning provided by APP demonstrated wide reach and has substantial potential to
      inform and impact behaviors of patients and caregivers. Continued efforts should
      be made to provide patient resources that address health literacy and patient
      education and respond to patient needs for better quality of life and improved
      health outcomes in pancreatic diseases.

PMID- 30286014
TI  - Pathophysiological Events Associated With Pancreatitis in Response to Tobacco: An
      In Vitro Comparative Study With Ethanol in Primary Acinar Cell Culture.
AB  - OBJECTIVES: The aim of this study was to comparatively analyze the effects of
      different concentrations of cigarette smoke condensate (CSC, a standardized
      tobacco extract) and ethanol on intracellular enzyme activation, cell necrosis,
      alteration of cytosolic calcium concentration ([Ca]c), and amylase secretion in
      pancreatic acinar cells. METHODS: The effects of CSC (1 MUg/mL to 0.4 mg/mL) and
      ethanol (10-100 mM) on intracellular enzyme activity, cell necrosis, and [Ca]c
      were measured by fluorescence assays in isolated pancreatic acinar cells. Amylase
      secretion was evaluated by spectrophotometry. Supramaximal concentrations of
      cholecystokinin (10-100 nM) were used as positive control. RESULTS: Neither CSC
      nor ethanol induced trypsin or elastase activation. Both CSC (0.1-0.4 mg/mL) and
      ethanol (10-75 mM) significantly increased [Ca]c. Amylase secretion was increased
      only in CSC-treated cells (0.3 and 0.4 mg/mL). After 60 minutes, CSC (0.3 and 0.4
      mg/mL) significantly increased acinar cell necrosis at a similar percentage to
      that induced by cholecystokinin. Ethanol did not induce any significant cell
      necrosis. CONCLUSIONS: Cigarette smoke condensate induces acinar cell injury and
      increases [Ca]c and amylase secretion, independently of intracellular enzyme
      activation, suggesting that tobacco could induce several main early events of
      pancreatitis in pancreatic acinar cells. However, ethanol only induces increases
      [Ca]c, having no effect on cell injury, amylase secretion, or intracellular
      enzyme activation.

PMID- 30286015
TI  - Predictive Factors for Autoimmune Pancreatitis Relapse After 3 Years of
      Maintenance Therapy.
AB  - OBJECTIVES: Oral corticosteroid treatment is the standard therapy for autoimmune
      pancreatitis (AIP) and is highly effective. However, relapse may occur during
      maintenance therapy (MT). We aimed to clarify the predictive factors for relapse
      after 3 years of MT for use in deciding on the continuation of long-term MT.
      METHODS: Among 56 retrospectively recruited AIP patients who received
      corticosteroid remission induction therapy followed by MT for a minimum of 5
      years, 38 subjects were enrolled after exclusion criteria and divided into the
      relapse group of patients who experienced relapse after 3 years of MT and the
      nonrelapse group of patients who did not. RESULTS: According to multivariate
      analysis, at least 4 other organ involvement numbers at diagnosis (hazard ratio,
      5.82; 95% confidence interval, 1.203-28.192) and IgG of 1400 mg/dL or greater at
      3 years of MT (hazard ratio, 4.41; 95% confidence interval, 1.096-17.790) were
      predictive factors for relapse after MT for 3 years, with patients exhibiting
      both predictive factors having a higher cumulative relapse rate than those with 1
      or fewer predictive factor. CONCLUSIONS: We uncovered 2 predictive factors for
      AIP relapse after 3 years of MT. These findings will assist in deciding
      corticosteroid therapy regimens at 3 years of MT to minimize AIP relapse risk and
      adverse corticosteroid effects.

PMID- 30286016
TI  - Concordance of the Balthazar Grade and the Revised Atlanta Classification:
      Proposing a Modified Balthazar Grade to Predict the Severity of Acute
      Pancreatitis in Pediatric Population.
AB  - OBJECTIVES: The aim of this study was to compare the concordance of the Balthazar
      grade and the revised Atlanta classification and then establish a modified
      radiological scoring system that would predict 3 degrees of severity of acute
      pancreatitis (AP) based on the latest Atlanta classification. METHODS: A
      retrospective study enrolling pediatric inpatients with AP who had completed
      computed tomography was conducted between January 2006 and March 2018. The
      concordance of the 2 radiological scoring systems was assessed with kappa
      statistic. RESULTS: The Balthazar grade was unable to accurately predict the
      severity of AP compared with the revised Atlanta classification. However, a
      modified Balthazar grading system defining patents with Balthazar grades A to C
      as mild, grade D as moderately, and grade E as severe presented perfect agreement
      with the revised Atlanta classification across the enrolled population (kappa,
      0.85; 95% confidence interval, 0.73-0.97). The concordance of the modified
      Balthazar score and the revised Atlanta classification remained a perfect degree
      of agreement across repeated tests in 90 random samples (kappa, 0.85; 95%
      confidence interval, 0.85-0.85). CONCLUSIONS: The modified Balthazar grade
      demonstrated perfect agreement with the latest Atlanta classification for AP
      severity scoring. As such, the modified Balthazar grade can be used to predict 3
      degrees of severity of AP.

PMID- 30286017
TI  - More Than Just a Game: The Public Health Impact of Sport and Physical Activity
      for People With Disabilities (The 2017 DeLisa Lecture).
AB  - Although people with disabilities make up a large proportion of our global
      population and are known to be disproportionately impacted by sedentary
      lifestyles leading to chronic disease, programs promoting physical activity often
      fail to address their unique needs. Both environmental and attitudinal factors
      also act as barriers to full participation. In this context, increasing evidence
      shows the positive impact of physical activity and sport on outcomes related to
      physical health, mental health, community participation, and, in some cases,
      neurorecovery for people with disabilities. Thus, participation should be seen
      not only as a medical intervention, but also as a rights-based issue. We, as
      physiatrists, can be agents of change by promoting concepts of universal design
      and inclusion in physical activity and sport programs.

PMID- 30286018
TI  - Distinct patterns of fiber type adaptation in rat hindlimb muscles 4 weeks after
      hemorrhagic stroke.
AB  - OBJECTIVE: The aim of this study was to evaluate adaptations in soleus (SOL) and
      tibialis anterior (TA) muscles in a rat model 4 weeks after hemorrhagic stroke.
      DESIGN: Young adult Sprague-Dawley rats were randomly assigned to two groups:
      stroke (STR) and control (CTRL), with 8 SOL and 8 TA muscles per group.
      Hemorrhagic stroke was induced in the right caudoputamen of the STR rats. CTRL
      rats had no intervention. Neurologic status was evaluated in both groups pre
      stroke, and four weeks post-stroke. Muscles were harvested after post-stroke
      neurologic testing. Muscle fiber types and cross-sectional areas were determined
      in SOL and TA using immunohistochemical labeling for myosin heavy chain (MHC).
      RESULTS: No generalized fiber atrophy was found in any of the muscles. Fiber
      types shifted from faster to slower in the TA of the STR group, but no fiber type
      shifts occurred in the SOL muscles of STR animals. CONCLUSION: Since slower MHC
      fiber types are associated with weaker contractile force and slower contractile
      speed, this faster-to-slower fiber type shift in TA muscles may contribute to
      weaker and slower muscle contraction in this muscle after stroke. This finding
      may indicate potential therapeutic benefit from treatments known to influence
      fiber type plasticity.

PMID- 30286019
TI  - Systematic Reviews and Meta-analytic Methods: Not All Are Created Equal.

PMID- 30286020
TI  - Role of Indocyanine Green Fluorescence Imaging in Preventing Anastomotic Leak in
      Colorectal Surgery: What Lies Ahead?

PMID- 30286021
TI  - Management of Trauma to the Rectum and Anus.

PMID- 30286022
TI  - Expert Commentary on Management of Trauma to the Rectum and Anus.

PMID- 30286023
TI  - Association Between Hospital and Surgeon Volume and Rectal Cancer Surgery
      Outcomes in Patients With Rectal Cancer Treated Since 2000: Systematic Literature
      Review and Meta-analysis.
AB  - BACKGROUND: Previous reviews and meta-analyses, which predominantly focused on
      patients treated before 2000, have reported conflicting evidence about the
      association between hospital/surgeon volume and rectal cancer outcomes. Given
      advances in rectal cancer resection, such as total mesorectal excision, it is
      essential to determine whether volume plays a role in rectal cancer outcomes
      among patients treated since 2000. OBJECTIVE: The purpose of this study was to
      determine whether there is an association between hospital/surgeon volume and
      rectal cancer surgery outcomes among patients treated since 2000. DATA SOURCES:
      We searched PubMed and EMBASE for articles published between January 2000 and
      December 29, 2017. STUDY SELECTION: Articles that analyzed the association
      between hospital/surgeon volume and rectal cancer outcomes were selected.
      INTERVENTION: Rectal cancer resection was the study intervention. MAIN OUTCOME
      MEASURES: The outcome measures of this study were surgical morbidity,
      postoperative mortality, surgical margin positivity, permanent colostomy rates,
      recurrence, and overall survival. RESULTS: Although 2845 articles were retrieved
      and assessed by the search strategy, 21 met the inclusion and exclusion criteria.
      There was a significant protective association between higher hospital volume and
      surgical morbidity (OR = 0.80 (95% CI, 0.70-0.93); I = 35%), permanent colostomy
      (OR = 0.51 (95% CI, 0.29-0.92); I = 34%), and postoperative mortality (OR = 0.62
      (95% CI, 0.43-0.88); I = 34%), and overall survival (OR = 0.99 (95% CI, 0.98
      1.00); I = 3%). Stratified analysis showed that the magnitude of association
      between hospital volume and rectal cancer surgery outcomes was stronger in the
      United States compared with other countries. Surgeon volume was not significantly
      associated with overall survival. The articles included in this analysis were
      high quality according to the Newcastle-Ottawa scale. Funnel plots suggested that
      the potential for publication bias was low. LIMITATIONS: Some articles included
      rectosigmoid cancers. CONCLUSIONS: Among patients diagnosed since 2000, higher
      hospital volume has had a significant protective effect on rectal cancer surgery
      outcomes.

PMID- 30286024
TI  - Real-Time Indocyanine Green Fluorescence Imaging-Guided Laparoscopic Right
      Hemicolectomy in Hepatic Flexural Colon Cancer.

PMID- 30286027
TI  - Some Exciting News and Changes for the Journal.

PMID- 30286025
TI  - Expert Commentary on Neoadjuvant Therapy for Rectal Cancer: Erratum.

PMID- 30286028
TI  - Evaluation of a Low-Cost, High-Fidelity Animal Model to Train Graduate Advanced
      Practice Nursing Students in the Performance of Ultrasound-Guided Central Line
      Catheter Insertion.
AB  - INTRODUCTION: Ultrasound-guided central venous catheter insertion (UGCVC) is a
      commonly performed procedure taught through simulation. The aims of the study
      were to examine the utilization of an animal model and compare it with two
      currently used Blue Phantom central line models to determine whether an animal
      model provides good or better simulated conditions for the performance of UGCVC
      insertion. METHODS: Using a randomized cross-over study, 46 advanced practice
      nursing students were assessed using a task-specific performance tool in their
      performance of UGCVC insertion on both the animal model and the Blue Phantom
      models. The number of insertion attempts and time to performance was recorded. A
      preprocedure survey was used to ascertain their presimulation workshop
      experience, followed by a postprocedure survey. A cost comparison was completed
      as a secondary outcome. RESULTS: A comparison was conducted on the performance
      scores and the postsurvey results between the animal model and the Blue Phantom
      models. The number of venous access attempts was not significantly different when
      comparing the three models. A cost comparison showed the total cost of each
      animal model was US $15.66 as compared with the approximate cost for the Blue
      Phantom IJ model of US $1500.00 and the Gen I model of US $2700.00. CONCLUSIONS:
      Current Blue Phantom models lack the ability to fully perform all the necessary
      steps critical to the performance of UGCVC insertion. At a total cost of US
      $15.66 per model, this study showed that training with an alternative economical
      model was comparable with more expensive mannequin simulators. The results of
      this study may serve to guide clinicians and educators who are seeking
      alternative simulation models to provide skill acquisition.

PMID- 30286029
TI  - The C. difficile puzzle: Putting it all together.
AB  - This article explores Clostridium difficile infection (CDI) versus colonization,
      regulations surrounding CDI reporting, the varied types of CDI testing methods
      available, and the important role nurses have in thoughtful submission of stool
      specimens for C. difficile testing.

PMID- 30286030
TI  - Enhanced recovery after cardiac surgery program to improve patient outcomes.
AB  - This article details the obstacles of implementing a cardiac-specific enhanced
      recovery after surgery (ERAS) program in a 919-bed not-for-profit community-based
      health system and the benefits of ERAS programs for different patient
      populations.

PMID- 30286031
TI  - Angiopoietin Level Trajectories in Toddlers with Severe Sepsis and Septic Shock
      and Their Effect on Capillary Endothelium.
AB  - OBJECTIVE: Angiopoietins are postulated diagnostic biomarkers in children and
      adults with severe sepsis and septic shock. The diagnostic value of angiopoietins
      in children less than 5 years old has not been established, nor has their effect
      on permeability in the capillary microvasculature. We aim to determine if levels
      of angiopoietin-1 or -2 (angpt-1, -2) are diagnostic for severe sepsis/shock in
      young children and whether they affect the permeability of cultured human dermal
      microvascular endothelial cells (HDMEC). DESIGN: Prospective observational study
      of children< 5 years old. Patients were classified as non-systemic inflammatory
      response syndrome (SIRS), SIRS/sepsis and severe sepsis/septic shock. SETTING:
      Tertiary care pediatric hospitals. PATIENTS: Critically ill children.
      INTERVENTIONS: None MEASUREMENTS:: Plasma angpt-1 and -2 levels were measured
      with ELISA. Expression of angpt-2 in endothelial cells was assessed with
      quantitative polymerase chain reaction. Permeability changes in cultured HDMECs
      were assessed with trans-endothelial electrical resistance (TEER) measurements.
      RESULTS: Angpt-1 levels were significantly higher in younger children compared to
      levels found in previous study of older children across disease severity (all p <
      0.001). Angpt-2 was significantly higher in this cohort with severe sepsis/septic
      shock compared to children without SIRS and SIRS/sepsis (all p < 0.003). Angpt
      2/1 ratio was also elevated in children with severe sepsis/septic shock but an
      order of magnitude less than older children (p < 0.02, p = 0.002). Angpt-1 and -2
      did not affect basal HDMEC permeability or modulate leak in isolation or in the
      presence of tumor necrosis factor (TNF). CONCLUSIONS: Angpt-2 levels and the
      angpt-2/1 ratio are appropriate diagnostic biomarkers of severe sepsis/septic
      shock in children less than 5 years old. Neither angpt-1 nor -2 affects basal
      HDMEC permeability alone or modulates TNF induced capillary leak.

PMID- 30286033
TI  - Enhancing Autophagy Protects Against Sepsis-Induced Neuromuscular Dysfunction
      Associated with Qualitative Changes to Acetylcholine Receptors.
AB  - Sepsis-induced myopathy is a heavy burden for patients during respiratory failure
      as well as after discharge, which could be characterized with qualitative changes
      to nAChR in a rat model of sepsis, regulated by NRG-1. Autophagy is an innate
      immune defense mechanism against microbial challenges. We found neuromuscular
      dysfunction in anterior tibial muscle of male Sprague-Dawley rats 24 h after
      cecal ligation and puncture (CLP). CLP resulted in increased systemic and local
      inflammation in anterior tibial muscle tissue. The start-up phase of autophagy,
      as measured by LC3II, was activated immediately after CLP and continued until 24
      h; the degradation phase was suppressed until 24 h, after a brief increase at 4 h
      (revealed by p62). NRG-1 first increased, and then decreased to a level lower
      than that in the sham group. Meanwhile, expression of gamma- and alpha7-
      acetylcholine receptors was detected at 8 and 16 h after CLP; levels increased
      continuously until 24 h. Subsequently, we investigated the significance of
      autophagy in CLP-induced neuromuscular dysfunction by treatment with rapamycin or
      3-methyladenine, which were classical pharmaceuticals for enhancing or
      suppressing autophagy. Rapamycin activated autophagy, limited the CLP-induced
      systemic pro-inflammatory response and blood bacterial load without affecting
      local inflammatory response, upregulated NRG-1, downregulated gamma- and alpha7
      acetylcholine receptors, and improved 7-day neuromuscular function and survival
      rate. In contrast, 3-methyladenine enhanced local inflammatory response,
      suppressed autophagy, worsened 7-day neuromuscular function. We conclude that
      impaired autophagy may contribute to sepsis-induced neuromuscular dysfunction in
      young male rats. Enhancing autophagy with rapamycin alleviated qualitative
      changes to acetylcholine receptors without triggering local anti-inflammatory
      response and improved anterior tibial muscle function in septic early phase (24
      h) as well as in septic chronic phase (7d). Enhancing autophagy soon after sepsis
      is a potential strategy for treatment of sepsis-induced myopathy.

PMID- 30286034
TI  - The Role of Mitochondrial DNA in The Development of Ischemia Reperfusion Injury.
AB  - Ischemia/reperfusion (I/R) injury is a common occurrence resulting from acute
      mesenteric ischemia, traumatic or septic shock, burns, and surgical procedures
      that can lead to multiple organ failure and high mortality in critically ill
      patients. Mitochondria are often considered as the cellular power factory via
      their capacity for ATP generation. Recently, mitochondria have been further
      identified as vital regulators of cell death, inflammation, and oxidative stress,
      all of which can aggravate I/R injury. Studies have indicated that mitochondrial
      DNA (mtDNA) damage leads to mitochondrial dysfunction and aggravates I/R injury.
      mtDNA is emerging as an agonist of the innate immune system that influences
      inflammatory pathology during I/R injury. In addition, when mtDNA is released
      into the cytoplasm, extracellular milieu or circulation, it can activate multiple
      pattern-recognition receptors to trigger type I interferon and pro-inflammatory
      responses. Here, we review the emerging role of mtDNA in I/R injury to highlight
      novel mechanistic insights and discuss the pathophysiological relevance of
      mitochondrial biology.

PMID- 30286032
TI  - Lactate is a Prognostic Factor in Patients Admitted with Suspected ST-Elevation
      Myocardial Infarction.
AB  - AIMS: The diagnosis of cardiogenic shock depends on clinical signs of poor
      perfusion and low blood pressure. Lactate concentration will increase with poor
      tissue perfusion, and it has prognostic value in cardiogenic shock patients. We
      sought to assess the prognostic value of lactate concentration in subjects
      admitted with suspected ST-elevation myocardial infarction (STEMI). METHODS AND
      RESULTS: In 2094 (93%) out of 2247 consecutive suspected STEMI-subjects, lactate
      concentration was measured on admission. The prognostic value of lactate
      concentration on 30-day mortality was assessed in addition to clinical signs of
      peripheral hypoperfusion, systolic blood pressure (sBP), and left ventricular
      ejection fraction (LVEF) in multivariable models.Lactate concentration added
      prognostic information beyond signs of peripheral hypoperfusion, sBP and LVEF,
      and was independently associated with 30-day mortality (Hazard ratio (95%
      confidence interval) 1.11 (1.07 - 1.14), p < 0.0001). Lactate also provided
      predictive information on 30-day mortality to the combination of signs of
      peripheral hypoperfusion, sBP, and LVEF (area under the receiver-operating
      characteristics curve = 0.88 vs. 0.83, p < 0.0001). CONCLUSIONS: In conclusion,
      admission lactate concentration in suspected STEMI-subjects contains prognostic
      information on 30-day mortality when added to variables used in cardiogenic shock
      definition. We recommend lactate measurement in STEMI-subjects, especially when
      signs of compromised hemodynamics are present.

PMID- 30286035
TI  - Circulating Monocyte Counts and its Impact on Outcomes in Patients with Severe
      Sepsis Including Septic Shock.
AB  - This study was performed to evaluate the association of monocyte counts with
      mortality, the rate of bacteremia and organ dysfunction and to evaluate whether
      the change in monocyte counts from the premorbid state to sepsis would differ
      between survivors and non-survivors in patients with severe sepsis including
      septic shock. A retrospective analysis of patients with severe sepsis including
      septic shock was performed. Monocyte counts were categorized into < 250, 250 -
      500, 500 - 750 and >= 750 cells/MUL; in addition, 28-day mortality, the rate of
      bacteremia and organ dysfunction were compared between the groups. Multivariate
      logistic regression analyses were performed to evaluate the independent
      association of initial blood cell counts with 28-day mortality. Subgroup analyses
      of patients who had premorbid data of blood cell counts were performed to
      evaluate the difference in the change in monocyte counts between survivors and
      non-survivors. During the study period, 2012 patients were included. Neutrophil
      and monocyte counts were significantly different between survivors and non
      survivors. However, only monocyte counts were independently associated with
      mortality in the multivariate logistic regression analyses. Patients with initial
      monocyte counts < 250 cells/MUL showed the highest mortality, rate of bacteremia
      and organ dysfunction. In patients who had premorbid blood cell counts, the
      monocyte counts increased in survivors but decreased in non-survivors from the
      premorbid to sepsis. In conclusion, monocyte counts were associated with
      mortality, the rate of bacteremia and organ dysfunction in patients with sepsis,
      possibly due to the relative lack of monocytopoiesis related with septic insults
      in non-survivors.

PMID- 30286036
TI  - Endoplasmic Reticulum Stress-Induced NLRP1 Inflammasome Activation Contributes to
      Myocardial Ischemia/Reperfusion Injury.
AB  - Studies have shown that Nod-like receptor protein (NLRP) 3 inflammasome
      activation contributes to myocardial ischemia/reperfusion (I/R) injury. However,
      the role and mechanism of NLRP1 inflammasome in myocardial I/R injury remains
      unknown. Endoplasmic reticulum (ER) stress is involved in the development of
      myocardial I/R injury. The relationship between ER stress and NLRP1 inflammasome
      in myocardial I/R injury needs further study. NLRP1 inflammasome activation and
      ER stress were investigated in hypoxia/reoxygenation (H/R)-treated primary mouse
      cardiomyocytes and left anterior descending coronary artery ligation and
      reperfusion mouse models. Downregulation of NLRP1 expression with NLRP1 siRNA was
      used to evaluate the role of NLRP1 inflammasome in H/R-stimulated cardiomyocyte
      injury. 4-phenylbutyric acid (4-PBA), an ER stress inhibitor, was used to
      pretreat cardiomyocytes before H/R treatment, the cardiomyocyte injury and NLRP1
      inflammasome activation were determined. Also, NF-kappaB signaling activity was
      measured. Additionally, PDTC, an NF-kappaB inhibitor, was used to treat
      cardiomyocytes before H/R stimulation and NLRP1 inflammasome activation was
      examined. We found the levels of ER stress markers GRP78, p-PERK, p-eIF2alpha and
      CHOP as well as NLRP1 inflammasome activation were significantly elevated both in
      vivo and in vitro. NLRP1 siRNA notably increased cell viability inhibited by H/R,
      suppressed H/R-induced cell apoptosis, LDH release and creatine kinase activity.
      4-PBA reduced H/R-stimulated cardiomyocyte injury via NLRP1 inflammasome
      inactivation, and it also suppressed NF-kappaB signaling activity. NLRP1
      inflammasome activation induced by H/R was also suppressed by PDTC. In
      conclusion, NLRP1 inflammasome activation promotes myocardial I/R injury. ER
      stress can activate NLRP1 inflammasome via activating the NF-kappaB signaling
      pathway.

PMID- 30286038
TI  - Recent progress in understanding immune activation in the pathogenesis in HIV
      tuberculosis co-infection.
AB  - PURPOSE OF REVIEW: Tuberculosis is the leading infectious cause of death
      worldwide, and HIV-1 the best recognized risk factor for active TB. This review
      focuses on immune complex formation; the interplay of type I and II interferon
      signaling; and T-cell activation in HIV-TB pathogenesis. RECENT FINDINGS:
      Circulating immune complexes and complement, and Fcgamma signaling in whole blood
      act as early markers of TB disease in HIV-1-infected persons. HIV-1 is associated
      with a type I interferon response in whole blood, reducing the specificity of TB
      biomarkers dependent on type I and II interferon genes. Type I and type II
      interferons are implicated in both protection and TB disease, a protective
      outcome may depend on modulating these pathways. Whilst M. tuberculosis-specific
      CD4 T cells are preferentially depleted during HIV-1 infection, activation
      markers on M. tuberculosis-specific CD4 T cells, in particular HLA-DR, reflect
      immune activation and have promise as biomarkers of M. tuberculosis disease
      activity in individuals with HIV-1. SUMMARY: TB pathogenesis in HIV-1 involves a
      complex interaction of underlying activation of both the innate and adaptive
      immune systems. Further research is required to understand whether biomarkers of
      activation could be used to predict or quantify TB disease in the context of HIV
      1 infection.

PMID- 30286039
TI  - Treatment of drug-resistant tuberculosis among people living with HIV.
AB  - PURPOSE OF REVIEW: This review aims to describe the key principles in treatment
      of drug-resistant tuberculosis (TB) in people living with HIV, including early
      access to timely diagnostics, linkage into care, TB treatment strategies
      including the use of new and repurposed drugs, co-management of HIV disease, and
      treatment complications and programmatic support to optimize treatment outcomes.
      These are necessary strategies to decrease the likelihood of poor treatment
      outcomes including lower treatment completion rates and higher mortality. RECENT
      FINDINGS: Diagnosis of drug-resistant TB is the gateway into care; yet
      understanding the utility and the limitations of genotypic methods in this
      population is necessary. The principles of TB treatment in HIV-infected
      individuals are similar to those without HIV co-infection, with few exceptions.
      However, adverse effects with potential significant morbidity may emerge during
      treatment, and timely antiretroviral therapy is essential to improve mortality in
      this patient population. Emerging data on the use of new and repurposed drugs and
      short course multidrug-resistant TB regimens and adherence strategies benefiting
      this population are reviewed. SUMMARY: The clinical complexity of co-managing
      drug-resistant TB and HIV, and the higher rate of poor treatment outcomes in this
      population demand careful clinical management strategies, and multidisciplinary
      and comprehensive programmatic interventions to optimize treatment success in
      this vulnerable group.

PMID- 30286040
TI  - HIV-associated pediatric tuberculosis: prevention, diagnosis and treatment.
AB  - PURPOSE OF REVIEW: The detrimental synergy of colliding HIV and tuberculosis (TB)
      epidemics is most devastating among children and adolescents living with HIV
      (CALWH) who shoulder a disproportionate burden of all child TB mortality. RECENT
      FINDINGS: CALWH benefit less from Bacille-Calmette Guerin vaccination than HIV
      uninfected children and are not receiving TB preventive therapy despite global
      recommendations. Further, the predictive utility of most diagnostic tools is
      reduced in CALWH. Finally, antiretroviral and anti-TB drug interactions continue
      to complicate cotreatment for children. Despite these challenges, recent data
      fuel a new awareness of TB as a hidden cause of child mortality and a renewed
      commitment to TB prevention. New diagnostic approaches using existing tools with
      novel specimens, such as stool, may improve the diagnosis of TB in CALWH.
      Further, pharmacokinetic studies and the development of new drug formulations
      promise better treatment options for CALWH in the near future. SUMMARY: With the
      awareness that TB is the leading cause of mortality among CALWH, comes a
      responsibility to accelerate research to prevent, diagnose and treat TB in this
      vulnerable population. In the present, we must adopt evidence-based preventive
      and treatment strategies to enhance outcomes of CALWH and combating TB.

PMID- 30286041
TI  - Preventive therapy for HIV-associated tuberculosis.
AB  - PURPOSE OF REVIEW: Tuberculosis (TB) remains the leading cause of death in people
      living with HIV (PLHIV) despite the achievements in antiretroviral therapy
      coverage. TB preventive therapy (TPT) has proved efficacy but has been neglected
      and poorly implemented. We reviewed recent publications and guidelines about TPT
      in PLHIV. RECENT FINDINGS: High-quality studies showed that TPT has a durable
      effect, over 5 years, preventing TB and all-cause mortality. There is new
      evidence showing the noninferiority of shorter, rifamycin-based regimens of TPT
      increasing the options for treatment. Recent studies describing robust
      implementation in different settings showed promising results for feasibility,
      tolerance, retention, and cost-effectiveness. New WHO recommendations, unifying
      previous versions, have been released to guide countries implementation. SUMMARY:
      New evidence support the scale up of TPT for PLHIV globally, further studies are
      needed to bring more evidence for specific populations, like pregnant women and
      for drug-drug interactions with antiretroviral agents.

PMID- 30286042
TI  - Identifying priorities for HIV-associated tuberculosis research through the WHO
      guidelines process.
AB  - PURPOSE OF REVIEW: Guidelines developed by the WHO aim to provide recommendations
      to support best practice in health delivery, with a focus on low-income and
      middle-income countries. As part of the guideline development process, critical
      knowledge gaps are identified and one of the core functions of WHO guidelines is
      to set forth priorities for future research. A review of research priorities
      identified through the WHO guideline development has recently been promoted as
      one approach to building an overarching priority research agenda in a given area.
      This paper outlines priorities for HIV-associated TB research identified in WHO
      HIV and TB guidelines published since 2015. RECENT FINDINGS: Nine guidelines were
      reviewed and 29 priority research questions were identified. Research priorities
      were identified for prevention of HIV-associated TB (11 questions), screening of
      latent and active TB in people living with HIV (six questions), treatment of drug
      sensitive (four questions), and drug-resistant (two questions) TB, and treatment
      of HIV in people coinfected with TB (three questions). SUMMARY: Multiple
      approaches to defining priority research questions for health research exist.
      Research priorities that arise from the WHO guideline development process are
      limited to those areas for which guidelines are developed. One strength of this
      approach is that it takes as a starting point a desire to make actionable
      recommendations for policy makers. WHO is working to further refine the
      formulation of research questions within the guideline development process.

PMID- 30286043
TI  - Tips for Making a Successful Online Microsurgery Educational Platform - The
      Experience of International Microsurgery Club.
AB  - The presence of online learning resources has grown tremendously in recent years.
      They provide powerful and yet easily accessible means of learning and sharing
      knowledge. Online learning resources now encompass all aspects of medicine, and
      microsurgery is no exception. International Microsurgery Club (IMC) is a closed,
      invitation-only group based on the Facebook social media platform. It was
      initiated on May 6, 2016, with primary objectives of providing a convenient forum
      for discussing challenging cases, sharing valuable resources, and providing
      opportunities for research collaboration. The membership of IMC has grown over
      8700 at two year of existence, and continues to expand. IMC has become one of the
      largest online platforms for global microsurgeons. Here, we share our experience
      on how to establish a successful online platform for medical education.

PMID- 30286044
TI  - Minimal pain with Prepectoral implant based breast reconstruction.

PMID- 30286045
TI  - Does reconstruction preserving the first or first two rays benefit over full
      transmetatarsal amputation in diabetic foot?
AB  - BACKGROUND: The benefits of total transmetatarsal amputation (TMA) over higher
      level amputation are well known. However, there are no studies evaluating the
      effects of first or the first two ray sparing transmetatarsal amputation with
      flap coverage. We evaluated this approach in regards to functional outcome and to
      identify long-term complications. MATERIAL AND METHOD: Retrospective data of 59
      patients were evaluated according to their surgical method. Complete TMA with
      free flap reconstruction was designated as group TMA with 27 patients and first
      or first two rays preserving TMA with free flap reconstruction was designated as
      group Ray with 32 patients. Demographics, flap outcomes, additional procedures
      after initial healing and functional outcomes were measured and evaluated.
      RESULTS: There was no statistical significant difference in demographic
      distribution and flap outcomes in either group except poor blood sugar control in
      group Ray. Additional procedures after initial healing showed no statistical
      difference but the tendency of minor procedures was higher in group Ray. The
      maximum achieved ambulatory function was significantly better in group Ray with
      an ambulatory function score of 4.4 over 3.7 in group TMA (p= 0.012). CONCLUSION:
      The preservation of the first or first two rays with free flap reconstruction may
      functionally benefit the patients despite the higher tendency of minor procedures
      after initial healing. Furthermore, the progressive deformity of the preserved
      first and second toes will inevitably occur requiring patients to undergo further
      surgery. Further studies are warranted to evaluate this approach.

PMID- 30286046
TI  - Current Use of Biological Scaffolds in Plastic Surgery.
AB  - Properly designed biodegradable scaffolds facilitate repair or regeneration of
      stromal tissues. Over the last 50 years, a variety of synthetic, semi-synthetic
      and decellularized scaffolds have been developed that provide surgeons with tools
      to reconstruct a wide array of structural defects.We reviewed the literature of
      biological degradable scaffolds in current clinical use in the US and highlight
      their design principles as well as products in common use.Host tissues populate
      scaffolds with inflammatory cells, fibroblasts, blood vessels, nerves and
      lymphatics. Cells lay down extracellular matrix macromolecules while enzymes
      degrade the scaffold. Over time the scaffold can be totally replaced by host
      tissues.The greatest use of scaffolds in plastic surgery is in skin replacement,
      breast reconstruction, abdominal wall reconstruction and peripheral nerve repair.
      Other areas of importance are cartilage and bone replacement as well as support
      for lining replacements such bowel, bladder, mucosa and dura. The wide range of
      research being done in this field is likely to provide surgeons with more choices
      and improved materials to repair and regenerate stromal structures.

PMID- 30286047
TI  - Assessing Quality of Life and Patient-Reported Satisfaction with Masculinizing
      Top Surgery: A Mixed-Methods Descriptive Survey Study.
AB  - BACKGROUND: Masculinizing top surgery (bilateral mastectomy with chest wall
      reconstruction) is an important gender-affirming procedure sought by many
      transmasculine and non-binary individuals. Current literature is primarily
      focused on details of surgical technique and complication rates, with limited
      data available on how top surgery affects subjective quality of life measures.
      METHODS: An anonymous online survey was distributed to 81 of the senior author's
      former top surgery patients. Survey response rate was 72% (58 respondents).
      Responses were analyzed to investigate quality of life, sexual confidence, mental
      health, satisfaction with top surgery, and patient attitudes toward top surgery's
      role in gender affirmation. RESULTS: Following top surgery, measures of quality
      of life and sexual confidence significantly improved (P < .001). Additionally,
      86% reported improvement in gender dysphoria-related mental health conditions.
      All but 1 respondent reported that top surgery had an overall positive impact on
      their life. CONCLUSIONS: Top surgery had major positive effects on all mental
      health and quality of life metrics. Our findings contribute to a much-needed body
      of evidence that top surgery markedly improves the daily lives and functioning of
      transgender and non-binary individuals who choose to undergo it.

PMID- 30286048
TI  - Reporting Adverse Events in Plastic Surgery: A Systematic Review of Randomized
      Controlled Trials.
AB  - BACKGROUND: Accurate knowledge of adverse events is critical for evaluation of
      the safety and efficacy of interventions. Historically, adverse events in
      surgical trials have been poorly reported. The objective of this study was to
      systematically evaluate the reporting of adverse events in randomized controlled
      trials (RCTs) in the plastic surgery literature. METHODS: Two independent
      reviewers conducted a systematic search using MEDLINE, EMBASE, and SCOPUS of the
      top seven plastic surgery journals with the highest impact factors. RCTs
      describing a potentially invasive treatment, published between January 2012 and
      December 2016, were included. RESULTS: One hundred and forty-five RCTs involving
      10,266 patients were included, of which 30% were registered. Anticipated adverse
      events were clearly defined in 15% of trials, and in 70% it was not clear who
      would be documenting adverse events. Furthermore, 72% of RCTs reported the
      occurrence of adverse events, of which 61% failed to report events occurring in
      the intra-interventional period. Of the trials not documenting any adverse event,
      two-thirds included a statement declaring that no adverse events had occurred.
      Binary logistic regression revealed that funded RCTs were 4.04 times more likely
      to report adverse events compared to non-funded RCTs (95% CI 1.41-10.83,
      p=0.009). CONCLUSIONS: Our findings suggest the need for reporting standards for
      adverse events in the plastic surgery literature, as such reporting remains
      heterogeneous and is lacking rigor. Improved quality and transparency is needed
      to strengthen evidenced-based practice and permit a balanced intervention
      assessment. This study provides a set of recommendations aimed at improving
      adverse event reporting.

PMID- 30286049
TI  - Sensory Modulation: An Important Piece of the Disability Puzzle for Adolescents
      with Persistent Pain.
AB  - OBJECTIVES: Sensory modulation patterns contribute to altered pain perception and
      disengagement in activities; atypical sensory modulation patterns have been
      associated with higher pain sensitivity, catastrophizing, and reduced function.
      Objectives of this study were to ascertain whether: adolescents with persistent
      pain had atypical sensory modulation patterns, atypical sensory modulation was
      associated with reduced functioning and higher pain, and pain catastrophizing
      mediated the relationship between sensory modulation and functional disability.
      METHODS: Adolescents (N=70, Females=63, Males=7) attending tertiary level
      interdisciplinary team assessment for persistent pain completed sensory
      modulation (Adolescent/Adult Sensory Profile), pain catastrophizing (Bath
      Adolescent Pain Questionnaire), pain intensity, functional disability (Functional
      Disability Index), and quality of life (Pediatric Quality of Life (QOL) Scales)
      questionnaires. RESULTS: Adolescents with persistent pain had atypical patterns
      of sensory modulation compared to normative data. Sensory modulation patterns
      were not associated with pain intensity; however, higher sensitivity was
      associated with greater disability (r=0.36, P<0.01), and lower registration of
      sensation was associated with poorer emotional (r=0.31, P<0.01), social (r=0.35,
      P<0.01), and school-related (r=0.49, P<0.001) QOL. Sensory modulation, pain
      intensity, and catastrophizing contributed independently to disability;
      catastrophizing mediated sensory sensitivity and both functional disability and
      emotional QOL. DISCUSSION: This study is the first to demonstrate that atypical
      sensory modulation patterns are associated with poorer function for adolescents
      with persistent pain, suggesting that individualized sensory-informed
      interventions can potentially facilitate participation in daily activities and
      improve QOL.

PMID- 30286051
TI  - QuickStats: Age-Adjusted Prevalence of Total, Diagnosed, and Undiagnosed
      Diabetes* Among Adults Aged >=20 Years - National Health and Nutrition
      Examination Survey, 1999-2000 to 2015-2016?.

PMID- 30286052
TI  - Outbreak of Salmonella Chailey Infections Linked To Precut Coconut Pieces -
      United States and Canada, 2017.
AB  - Foodborne salmonellosis causes an estimated 1 million illnesses and 400 deaths
      annually in the United States (1). In recent years, salmonellosis outbreaks have
      been caused by foods not typically associated with Salmonella. On May 2, 2017,
      PulseNet, CDC's national molecular subtyping network for foodborne disease
      surveillance, identified a cluster of 14 Salmonella Chailey isolates with a rare
      pulsed-field gel electrophoresis (PFGE) pattern. On May 29, Canadian health
      officials informed CDC that they were also investigating a cluster of five
      Salmonella Chailey infections in British Columbia with the same PFGE pattern.
      Nineteen cases were identified and investigated by CDC, U.S. state health
      departments, the Public Health Agency of Canada, and the British Columbia Centre
      for Disease Control. Isolates from all cases were highly related by whole genome
      sequencing (WGS). Illness onset dates ranged from March 10 to May 7, 2017.
      Initial interviews revealed that infected persons consumed various fresh foods
      and shopped at grocery chain A; focused questionnaires identified precut coconut
      pieces from grocery chain A as a common vehicle. The Canadian Food Inspection
      Agency (CFIA) and the U.S. Food and Drug Administration (FDA) conducted a
      traceback investigation that implicated a single lot of frozen, precut coconut as
      the outbreak source. Grocery chain A voluntarily removed precut coconut pieces
      from their stores. This action likely limited the size and scope of this
      outbreak.

PMID- 30286050
TI  - Rs4938723 Polymorphism Is Associated with Susceptibility to Hepatocellular
      Carcinoma Risk and Is a Protective Factor in Leukemia, Colorectal, and Esophageal
      Cancer.
AB  - BACKGROUND Growing evidence indicates that a non-coding RNA named miR-34b/c plays
      crucial roles in carcinogenesis, and its common polymorphism, pri-miR-34b/c
      rs4938723, also participates in this process and is associated with cancer
      susceptibility. However, this association was previously undefined and ambiguous.
      Therefore, we carried out an updated analysis to evaluate this relationship
      between rs4938723 polymorphism and cancer susceptibility. MATERIAL AND METHODS
      PubMed, EMbase, Web of Science and Chinese language (WanFang, CNKI and VIP)
      databases were searched for relevant studies until Sep 10, 2018. Odds ratios and
      95% confidence interval were applied to assess this relationship. RESULTS Thirty
      case-control studies were retrieved. No positive association was found in either
      the overall study population or in the subgroups, based on ethnicity, source of
      group, sex, smoking, and drinking status. The main results were observed in the
      stratified analysis subgroups in cancer type subgroup: rs4938723 polymorphism may
      be a protective factor in leukemia, colorectal cancer, and esophageal cancer;
      however, C-allele was a risk factor in carriers for hepatocellular carcinoma.
      Last but not the least, poor positive results were discovered in the age
      subgroup. CONCLUSIONS Current meta-analysis suggested that rs4938723 polymorphism
      was potentially associated with hepatocellular carcinoma risk, but this
      polymorphism had a decreased association for susceptibility to esophageal cancer,
      leukemia, and colorectal cancer. Furthermore, studies with larger sample sizes
      and including gene-gene or gene-environment interactions should be carried out to
      elucidate the role of rs4938723 polymorphism in cancer risk.

PMID- 30286054
TI  - Notes from the Field: Lead Exposures Among Employees at a Bullet Manufacturing
      Company - Missouri, 2017.

PMID- 30286053
TI  - Symptoms of Anxiety and Depression Among Adults with Arthritis - United States,
      2015-2017.
AB  - An estimated 54.4 million (22.7%) U.S. adults have doctor-diagnosed arthritis
      (1). A report in 2012 found that, among adults aged >=45 years with arthritis,
      approximately one third reported having anxiety or depression, with anxiety more
      common than depression (2). Studies examining mental health conditions in adults
      with arthritis have focused largely on depression, arthritis subtypes, and middle
      aged and older adults, or have not been nationally representative (3). To address
      these knowledge gaps, CDC analyzed 2015-2017 National Health Interview Survey
      (NHIS) data* to estimate the national prevalence of clinically relevant symptoms
      of anxiety and depression among adults aged >=18 years with arthritis. Among
      adults with arthritis, age-standardized prevalences of symptoms of anxiety and
      depression were 22.5% and 12.1%, respectively, compared with 10.7% and 4.7% among
      adults without arthritis. Successful treatment approaches to address anxiety and
      depression among adults with arthritis are multifaceted and include screenings,
      referrals to mental health professionals, and evidence-based strategies such as
      regular physical activity and participation in self-management education to
      improve mental health.

PMID- 30286055
TI  - Notes from the Field: Multiple Cyclosporiasis Outbreaks - United States, 2018.

PMID- 30286056
TI  - Factors Contributing to Congenital Syphilis Cases - New York City, 2010-2016.
AB  - Congenital syphilis occurs when syphilis is transmitted from a pregnant woman to
      her fetus; congenital syphilis can be prevented through screening and treatment
      during pregnancy. Transmission to the fetus can occur at any stage of maternal
      infection, but is more likely during primary and secondary syphilis, with rates
      of transmission up to 100% at these stages (1). Untreated syphilis during
      pregnancy can cause spontaneous abortion, stillbirth, and early infant death.
      During 2013-2017, national rates of congenital syphilis increased from 9.2 to
      23.3 cases per 100,000 live births (2), coinciding with increasing rates of
      primary and secondary syphilis among women of reproductive age (3). In New York
      City (NYC), cases of primary and secondary syphilis among women aged 15-44 years
      increased 147% during 2015-2016. To evaluate measures to prevent congenital
      syphilis, the NYC Department of Health and Mental Hygiene (DOHMH) reviewed data
      for congenital syphilis cases reported during 2010-2016 and identified patient-,
      provider-, and systems-level factors that contributed to these cases. During this
      period, 578 syphilis cases among pregnant women aged 15-44 years were reported to
      DOHMH; a congenital syphilis case was averted or otherwise failed to occur in 510
      (88.2%) of these pregnancies, and in 68, a case of congenital syphilis occurred
      (eight cases per 100,000 live births).* Among the 68 pregnant women associated
      with these congenital syphilis cases, 21 (30.9%) did not receive timely (>=45
      days before delivery) prenatal care. Among the 47 pregnant women who did access
      timely prenatal care, four (8.5%) did not receive an initial syphilis test until
      <45 days before delivery, and 22 (46.8%) acquired syphilis after an initial
      nonreactive syphilis test. These findings support recommendations that health
      care providers screen all pregnant women for syphilis at the first prenatal care
      visit and then rescreen women at risk in the early third trimester.

PMID- 30286057
TI  - Notes from the Field: Spatially Associated Coincident and Noncoincident Cases of
      La Crosse Encephalitis - North Carolina, 2002-2017.

PMID- 30286059
TI  - Changing trauma systems and outcomes as advances in medicine and collection of
      data improve.

PMID- 30286058
TI  - Rates of Carpal Tunnel Syndrome in a State Workers' Compensation Information
      System, by Industry and Occupation - California, 2007-2014.
AB  - Carpal tunnel syndrome (CTS) occurs when the median nerve becomes compressed as
      it passes through the wrist within the carpal tunnel, resulting in pain,
      tingling, weakness, or numbness in the hand or the wrist. Occupational risk
      factors for CTS include engaging in work activities that require forceful,
      repetitive tasks, prolonged use of the hands or wrists in an awkward posture, or
      vibration (1). To assess trends and identify high-risk industries and occupations
      for CTS, the California Department of Public Health (CDPH) analyzed California
      workers' compensation claims for CTS by industry (2007-2014) and occupation
      (2014) and calculated rates per full-time equivalent (FTE) worker. During 2007
      2014, a total of 139,336 CTS cases were reported (incidence = 6.3 cases per
      10,000 FTE) in California workers; the rate among women (8.2) was 3.3 times
      higher than that among men (2.5). Industries with the highest rates of CTS were
      textile, fabric finishing, and coating mills (44.9), apparel accessories and
      other apparel manufacturing (43.1), and animal slaughtering and processing
      (39.8). Industries with high rates of CTS should consider implementing
      intervention measures, including ergonomic evaluations and development of tools
      and instruments that require less repetition and force and that correct awkward
      postures.

PMID- 30286060
TI  - Use of tranexamic acid in trauma patients requiring massive transfusion protocol
      activation: an audit in a major trauma centre in New Zealand.
AB  - AIM: To investigate prescribing behaviours around tranexamic acid (TXA) use in
      the early management of severe trauma, and compare against standards considered
      to be best practice internationally, as established by the current body of
      research. METHODS: We undertook a retrospective analysis of all trauma patients
      requiring massive transfusion protocol (MTP) activation across a 20-month period.
      A combination of physical and electronic inpatient records and ambulance
      documentation were reviewed to determine dose and timing of TXA administration.
      RESULTS: During the period studied, 27 adult trauma patients who required
      activation of the MTP were identified. Of the patients where TXA was indicated,
      76.2% received at least an initial dose of TXA, with 19.0% receiving both doses.
      21.1% of patients who received TXA were administered an initial dose within one
      hour of injury, 52.6% between one and three hours, 26.3% outside three hours.
      CONCLUSIONS: TXA was found to be under-utilised and significant departures from
      best practice were found, likely due to persisting uncertainty and unfamiliarity.
      In particular, delayed administration beyond the three-hour therapeutic window
      occurred in a quarter of patients, increasing the risk of mortality secondary to
      haemorrhage. This pattern of use may apply to the wider population of trauma
      patients in this centre, and requires remedy and reassessment.

PMID- 30286061
TI  - Livestock-related injuries in the Midland region of New Zealand.
AB  - AIM: To assess the incidence and patterns of injury resulting from force
      transferred from large livestock in the Midland Region of New Zealand, and to
      identify foci for prevention. METHOD: Data was sourced from the Midland Trauma
      System Registry. Patients admitted to Midland hospitals from 2012 to 2015 were
      evaluated. Data included patient demography, location, mechanism, and time of the
      injury, type of animals involved, injuries sustained, interventions, outcomes and
      hospital costs. The final sample included 168 injury events. RESULTS: 75.6% were
      due to interactions with cattle. The remainder were from sheep, pigs and deer.
      Most of the injuries were either 'hit', 'crush' or 'kick' injuries. Moving and
      loading stock resulted in 38% of the injuries, and 29% occurred near fences,
      gates or poles. Cattle-related injuries peaked during September and October.
      Sheep-related injuries peaked in December. These months correspond to calving
      season in cows and shearing season in sheep. Injury peaks were observed in the 20
      29 and 50-59 age groups. CONCLUSION: This study has identified high-risk animals,
      activities, age intervals and times during which large livestock-related injuries
      may occur, and revealed the significant impact on hospitals and communities that
      these injuries result in.

PMID- 30286062
TI  - Audit of ethnicity data in the Waikato Hospital Patient Management System and
      Trauma Registry: pilot of the Hospital Ethnicity Data Audit Toolkit.
AB  - BACKGROUND: Maori are disproportionately impacted by injury in New Zealand,
      therefore reliable ethnicity data are essential for measuring and addressing
      inequities in trauma incidence, care and outcomes. AIM: To audit the quality of
      ethnicity data captured by the Waikato Hospital Trauma Registry and Waikato
      Hospital patient management system against self-identified ethnicity. METHOD:
      Self-identified ethnicity using the New Zealand Census ethnicity question was
      gathered from 100 consecutive trauma patients and compared with ethnicity
      recorded in their Trauma Registry record and in the hospital's patient management
      database. RESULTS: Twenty-nine (29%) participants self-identified as Maori, of
      whom six were classified as New Zealand European (NZE) only in the Trauma
      Registry and five as NZE on the hospital patient management database. Over half
      of Maori (n=18/29) reported more than one ethnicity compared with 4% (n=3/71) of
      non-Maori. Self-identified ethnicity matched Trauma Registry ethnicity for one
      quarter (n=7/29) of Maori versus 9% of non-Maori. CONCLUSIONS: The degree of
      misclassification of Maori ethnicity data among patients in the Waikato Trauma
      Registry and the Waikato Hospital patient management system highlights a need for
      improvements to how ethnicity data is captured within these databases and
      potentially many other similar entities collecting ethnicity data in New Zealand.
      The release of revised standardised protocols for the collection of ethnicity
      data is timely given the recent establishment of a national trauma registry.
      Without quality data, the opportunity to investigate and address ethnic
      inequities in trauma incidence and management is greatly compromised.

PMID- 30286063
TI  - New Zealanders' experiences and pathways to a diagnosis of bowel cancer: a cross
      sectional descriptive study of a younger cohort.
AB  - AIMS: To understand colorectal cancer (CRC) symptoms experienced by Aotearoa/New
      Zealand patients and to describe patient-experienced pathways and factors which
      may be associated with delayed diagnosis. METHODS: Ninety-eight patients
      diagnosed with CRC, recruited via a national charity, completed a questionnaire.
      Questions included demographics, symptoms, help-seeking and diagnostic pathways
      followed. RESULTS: Of 98 participants, 72 (73%) were aged under 60 years; most
      were symptomatic (n=93, 95%) and first discussed symptoms with someone who was
      not a healthcare professional (HCP) (n=71, 79%). The first HCP approached was
      usually a general practitioner (n=81, 83%). Symptom-to-diagnosis interval (SDI)
      was often six months or more (n=52, 56%) among our younger cohort. Delay was more
      likely if patients were younger (P=0.05), without a tertiary qualification
      (P=0.03), reported a poor/neutral experience at their first related HCP
      appointment (P=0.02), or were diagnosed in the public sector (P=0.01).
      CONCLUSIONS: Few patients initially suspected bowel cancer or reported
      embarrassment seeking care; those who did were most likely to experience changes
      in bowel habit or bleeding. Our study is small, and not representative of all
      those diagnosed with CRC in New Zealand; yet it provides important first insights
      into patients' diagnostic experiences.

PMID- 30286064
TI  - Alcohol-related emergency department attendances after the introduction of the
      Sale and Supply of Alcohol Act 2012.
AB  - AIM: To measure changes in alcohol-related emergency department (ED) attendances
      after introduction of the Sale and Supply of Alcohol Act 2012. METHODS: Cross
      sectional survey of Christchurch ED attendees in three-week sampling periods in
      2013 and 2017. Participants had consumed alcohol within four hours, or their
      drinking had directly contributed to the attendance. The quantity of alcohol
      consumed and places of purchase and consumption for the index drinking episode
      were recorded. RESULTS: From 2013 to 2017 there was a non-significant (p=.41)
      reduction in the proportion of ED attendees eligible for the study, from 253/3400
      (7.4%) to 258/3721 (6.9%). Among participants (n=169 in 2013, n=139 in 2017),
      liquor store purchasing increased from 41.7% in 2013 to 56.1% in 2017 (p<.01) but
      there was no significant change in quantity consumed in the index episode; last
      drink location; percentage of participants with an injury-related attendance; or
      pre-drinking. In both waves, most participants had purchased alcohol from off
      licence venues and consumed their last drink at a private location. CONCLUSION:
      Alcohol-related ED attendances remained common after the Sale and Supply of
      Alcohol Act 2012 was introduced, and they mainly occurred in people who sourced
      alcohol from off-licence outlets and had their last drink at private locations.

PMID- 30286065
TI  - Equine-related injuries requiring hospitalisation in the Midland Region of New
      Zealand: a continuous five-year review.
AB  - AIM: To examine the pattern and outcomes of equine-related injuries for
      hospitalised patients in the Midland Region of New Zealand over a five-year
      period. METHOD: A retrospective review of all patients admitted to hospitals
      within the Midland region of New Zealand with an injury date 1 January 2012-31
      December 2016, as a direct result of equine-related trauma. RESULTS: Seven
      hundred and one patients were admitted due to equine-related injuries, 6.6% were
      major trauma events (Injury Severity Scale >12), with nearly half of all injuries
      (47.3%) to the extremities. Mean age was 36 years (median 38 years), and 69% were
      females. The most common mechanisms of injury were falls from horse (70.6%),
      kicked (12.7%) and knocked (6.7%) by the horse. Males were more likely to have a
      non-fall injury. Average length of stay (all patients) was 3.4 days, and half of
      all patients required surgery. All patients survived. At Waikato Hospital, the
      largest district hospital in the region, the average inpatient cost was
      NZ$7,805/patient. CONCLUSION: The study has identified the demography, injury
      types, risk factors and outcomes for equine-related injuries in the Midland
      Region of New Zealand. Indications are that the severity of such injuries may be
      less than previously reported. However, the volumes and costs of injury represent
      a significant burden on the health system, individuals and communities. More
      detailed understanding of causative factors will allow targeting of prevention
      strategies to address high-risk activities and demographic groups.

PMID- 30286066
TI  - Conflict of interest and alcohol discourse-a new face but familiar messages.
AB  - The launch of a new alcohol industry body, the Alcohol Beverages Council,
      provides an active voice in the media debate on alcohol policy in New Zealand.
      The Council's messages are the usual ones offered by the alcohol industry: a
      focus on the drinker, not the product; protection of the rights of the moderate
      drinker; arguments for education; and erroneous statements about evidence-based
      policies. At the global level these messages, in the context of corporate social
      responsibility and lobbying activities, have been successful in subverting
      effective policy. A similar lack of policy implementation has happened in New
      Zealand. Underpinning the industry lobbying is the need to protect their sales
      and profits, 46% of which, in New Zealand, are derived from very heavy alcohol
      consumption. It is important policy makers and media recognise the conflict of
      interest inherent in these messages.

PMID- 30286067
TI  - Colloidal silver optic neuropathy.

PMID- 30286068
TI  - Surgical aortic valve replacement for valve-in-valve trans-catheter aortic valve
      dysfunction in the patient with a small aortic annulus.

PMID- 30286069
TI  - The fault in his seeds: Lost notes to the case of bias in Samuel George Morton's
      cranial race science.
AB  - The discovery of nearly 180-year-old cranial measurements in the archives of 19th
      century American physician and naturalist Samuel George Morton can address a
      lingering debate, begun in the late 20th century by paleontologist and historian
      of science Stephen Jay Gould, about the unconscious bias alleged in Morton's
      comparative data of brain size in human racial groups. Analysis of Morton's lost
      data and the records of his studies does not support Gould's arguments about
      Morton's biased data collection. However, historical contextualization of Morton
      with his scientific peers, especially German anatomist Friedrich Tiedemann,
      suggests that, while Morton's data may have been unbiased, his cranial race
      science was not. Tiedemann and Morton independently produced similar data about
      human brain size in different racial groups but analyzed and interpreted their
      nearly equivalent results in dramatically different ways: Tiedemann using them to
      argue for equality and the abolition of slavery, and Morton using them to
      entrench racial divisions and hierarchy. These differences draw attention to the
      epistemic limitations of data and the pervasive role of bias within the broader
      historical, social, and cultural context of science.

PMID- 30286070
TI  - Birds, blooms, and evolving diversity.
AB  - In this Open Highlight, Senior Editor Lauren Richardson features exciting new
      Open Access research into how species evolve their characteristic traits.

PMID- 30286072
TI  - Ten simple rules for scientists: Improving your writing productivity.

PMID- 30286071
TI  - A systems biology approach uncovers the core gene regulatory network governing
      iridophore fate choice from the neural crest.
AB  - Multipotent neural crest (NC) progenitors generate an astonishing array of
      derivatives, including neuronal, skeletal components and pigment cells
      (chromatophores), but the molecular mechanisms allowing balanced selection of
      each fate remain unknown. In zebrafish, melanocytes, iridophores and
      xanthophores, the three chromatophore lineages, are thought to share progenitors
      and so lend themselves to investigating the complex gene regulatory networks
      (GRNs) underlying fate segregation of NC progenitors. Although the core GRN
      governing melanocyte specification has been previously established, those guiding
      iridophore and xanthophore development remain elusive. Here we focus on the
      iridophore GRN, where mutant phenotypes identify the transcription factors Sox10,
      Tfec and Mitfa and the receptor tyrosine kinase, Ltk, as key players. Here we
      present expression data, as well as loss and gain of function results, guiding
      the derivation of an initial iridophore specification GRN. Moreover, we use an
      iterative process of mathematical modelling, supplemented with a Monte Carlo
      screening algorithm suited to the qualitative nature of the experimental data, to
      allow for rigorous predictive exploration of the GRN dynamics. Predictions were
      experimentally evaluated and testable hypotheses were derived to construct an
      improved version of the GRN, which we showed produced outputs consistent with
      experimentally observed gene expression dynamics. Our study reveals multiple
      important regulatory features, notably a sox10-dependent positive feedback loop
      between tfec and ltk driving iridophore specification; the molecular basis of
      sox10 maintenance throughout iridophore development; and the cooperation between
      sox10 and tfec in driving expression of pnp4a, a key differentiation gene. We
      also assess a candidate repressor of mitfa, a melanocyte-specific target of
      sox10. Surprisingly, our data challenge the reported role of Foxd3, an
      established mitfa repressor, in iridophore regulation. Our study builds upon our
      previous systems biology approach, by incorporating physiologically-relevant
      parameter values and rigorous evaluation of parameter values within a qualitative
      data framework, to establish for the first time the core GRN guiding
      specification of the iridophore lineage.

PMID- 30286073
TI  - A Kirchhoff-Nernst-Planck framework for modeling large scale extracellular
      electrodiffusion surrounding morphologically detailed neurons.
AB  - Many pathological conditions, such as seizures, stroke, and spreading depression,
      are associated with substantial changes in ion concentrations in the
      extracellular space (ECS) of the brain. An understanding of the mechanisms that
      govern ECS concentration dynamics may be a prerequisite for understanding such
      pathologies. To estimate the transport of ions due to electrodiffusive effects,
      one must keep track of both the ion concentrations and the electric potential
      simultaneously in the relevant regions of the brain. Although this is currently
      unfeasible experimentally, it is in principle achievable with computational
      models based on biophysical principles and constraints. Previous computational
      models of extracellular ion-concentration dynamics have required extensive
      computing power, and therefore have been limited to either phenomena on very
      small spatiotemporal scales (micrometers and milliseconds), or simplified and
      idealized 1-dimensional (1-D) transport processes on a larger scale. Here, we
      present the 3-D Kirchhoff-Nernst-Planck (KNP) framework, tailored to explore
      electrodiffusive effects on large spatiotemporal scales. By assuming
      electroneutrality, the KNP-framework circumvents charge-relaxation processes on
      the spatiotemporal scales of nanometers and nanoseconds, and makes it feasible to
      run simulations on the spatiotemporal scales of millimeters and seconds on a
      standard desktop computer. In the present work, we use the 3-D KNP framework to
      simulate the dynamics of ion concentrations and the electrical potential
      surrounding a morphologically detailed pyramidal cell. In addition to elucidating
      the single neuron contribution to electrodiffusive effects in the ECS, the
      simulation demonstrates the efficiency of the 3-D KNP framework. We envision that
      future applications of the framework to more complex and biologically realistic
      systems will be useful in exploring pathological conditions associated with large
      concentration variations in the ECS.

PMID- 30286074
TI  - Rhinoceros beetle horn development reveals deep parallels with dung beetles.
AB  - Beetle horns are attractive models for studying the evolution of novel traits, as
      they display diverse shapes, sizes, and numbers among closely related species
      within the family Scarabaeidae. Horns radiated prolifically and independently in
      two distant subfamilies of scarabs, the dung beetles (Scarabaeinae), and the
      rhinoceros beetles (Dynastinae). However, current knowledge of the mechanisms
      underlying horn diversification remains limited to a single genus of dung
      beetles, Onthophagus. Here we unveil 11 horn formation genes in a rhinoceros
      beetle, Trypoxylus dichotomus. These 11 genes are mostly categorized as larval
      head- and appendage-patterning genes that also are involved in Onthophagus horn
      formation, suggesting the same suite of genes was recruited in each lineage
      during horn evolution. Although our RNAi analyses reveal interesting differences
      in the functions of a few of these genes, the overwhelming conclusion is that
      both head and thoracic horns develop similarly in Trypoxylus and Onthophagus,
      originating in the same developmental regions and deploying similar portions of
      appendage patterning networks during their growth. Our findings highlight deep
      parallels in the development of rhinoceros and dung beetle horns, suggesting
      either that both horn types arose in the common ancestor of all scarabs, a
      surprising reconstruction of horn evolution that would mean the majority of
      scarab species (~35,000) actively repress horn growth, or that parallel origins
      of these extravagant structures resulted from repeated co-option of the same
      underlying developmental processes.

PMID- 30286075
TI  - Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced
      dermonecrosis.
AB  - Envenomings by snakebites constitute a serious and challenging global health
      issue. The mainstay in the therapy of snakebite envenomings is the parenteral
      administration of animal-derived antivenoms. Significantly, antivenoms are only
      partially effective in the control of local tissue damage. A novel approach to
      mitigate the progression of local tissue damage that could complement the
      antivenom therapy of envenomings is proposed. We describe an abiotic hydrogel
      nanoparticle engineered to bind to and modulate the activity of a diverse array
      of PLA2 and 3FTX isoforms found in Elapidae snake venoms. These two families of
      protein toxins share features that are associated with their common (membrane)
      targets, allowing for nanoparticle sequestration by a mechanism that differs from
      immunological (epitope) selection. The nanoparticles are non-toxic in mice and
      inhibit dose-dependently the dermonecrotic activity of Naja nigricollis venom.

PMID- 30286076
TI  - Community-based prevalence of typhoid fever, typhus, brucellosis and malaria
      among symptomatic individuals in Afar Region, Ethiopia.
AB  - BACKGROUND: In sub-Saharan Africa, where there is the scarcity of proper
      diagnostic tools, febrile illness related symptoms are often misdiagnosed as
      malaria. Information on causative agents of febrile illness related symptoms
      among pastoral communities in Ethiopia have rarely been described. METHODS: In
      this a community based cross-sectional survey, we assessed the prevalence of
      typhoid fever, typhus, brucellosis and malaria among individuals with a set of
      given symptoms in Amibara district, Afar Region, Ethiopia. Blood samples were
      collected from 650 study participants, and examined by Widal and Weilfelix direct
      card agglutination test (DCAT) as well as test tube based titration test for
      Salmonella enterica serotype Typhi (S. Typhi) and Rickettsia infections. Rose
      Bengal Plate Test (RBPT) and Complement Fixation Test (CFT) were used to screen
      Brucella infection. Thin and thick blood smears were used to diagnosis malaria.
      RESULTS: Out of 630 sera screened by DCAT, 83 (13.2%) were reactive to H and/or O
      antigens for S. Typhi infection. Among these, 46 (55.4%) were reactive by the
      titration test at the cut off value >= 1:80. The combined sero-prevalence for S.
      Typhi by the two tests was 7.3% (46/630). The seroprevalence for Rickettsia
      infection was 26.2% (165/630) by DCAT and 53.3% (88/165) by the titration test at
      the cut off value >= 1:80. The combined sero-prevalence for Rickettsia infection
      by the two tests was 14.0% (88/630). The sero-prevalence for Brucella infection
      was 12.7% (80/630) by RBPT, of which 28/80 (35%) were positive by CFT. The
      combined sero-prevalence for Brucella infection by the two tests was 4.4%
      (28/630). Out 650 suspected individuals for malaria, 16 (2.5%) were found
      positive for P. falciparum infection. CONCLUSION: In this study, typhoid fever,
      typhus, brucellosis and malaria were observed among symptomatic individuals. The
      study also highlighted that brucellosis cases can be misdiagnosed as malaria or
      other disease based solely on clinical diagnosis. Therefore, efforts are needed
      to improve disease awareness and laboratory services for the diagnosis of
      brucellosis and other zoonotic diseases to identify other causes of febrile
      illness in this pastoral setting.

PMID- 30286077
TI  - Prediction of gene regulatory enhancers across species reveals evolutionarily
      conserved sequence properties.
AB  - Genomic regions with gene regulatory enhancer activity turnover rapidly across
      mammals. In contrast, gene expression patterns and transcription factor binding
      preferences are largely conserved between mammalian species. Based on this
      conservation, we hypothesized that enhancers active in different mammals would
      exhibit conserved sequence patterns in spite of their different genomic
      locations. To investigate this hypothesis, we evaluated the extent to which
      sequence patterns that are predictive of enhancers in one species are predictive
      of enhancers in other mammalian species by training and testing two types of
      machine learning models. We trained support vector machine (SVM) and
      convolutional neural network (CNN) classifiers to distinguish enhancers defined
      by histone marks from the genomic background based on DNA sequence patterns in
      human, macaque, mouse, dog, cow, and opossum. The classifiers accurately
      identified many adult liver, developing limb, and developing brain enhancers, and
      the CNNs outperformed the SVMs. Furthermore, classifiers trained in one species
      and tested in another performed nearly as well as classifiers trained and tested
      on the same species. We observed similar cross-species conservation when applying
      the models to human and mouse enhancers validated in transgenic assays. This
      indicates that many short sequence patterns predictive of enhancers are largely
      conserved. The sequence patterns most predictive of enhancers in each species
      matched the binding motifs for a common set of TFs enriched for expression in
      relevant tissues, supporting the biological relevance of the learned features.
      Thus, despite the rapid change of active enhancer locations between mammals,
      cross-species enhancer prediction is often possible. Our results suggest that
      short sequence patterns encoding enhancer activity have been maintained across
      more than 180 million years of mammalian evolution.

PMID- 30286081
TI  - Correction: Comparison of artemether-lumefantrine and chloroquine with and
      without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A
      randomized controlled trial.
AB  - [This corrects the article DOI: 10.1371/journal.pmed.1002299.].

PMID- 30286080
TI  - Association between ambient air pollution and daily hospital admissions for
      ischemic stroke: A nationwide time-series analysis.
AB  - BACKGROUND: Evidence of the short-term effects of ambient air pollution on the
      risk of ischemic stroke in low- and middle-income countries is limited and
      inconsistent. We aimed to examine the associations between air pollution and
      daily hospital admissions for ischemic stroke in China. METHODS AND FINDINGS: We
      identified hospital admissions for ischemic stroke in 2014-2016 from the national
      database covering up to 0.28 billion people who received Urban Employee Basic
      Medical Insurance (UEBMI) in China. We examined the associations between air
      pollution and daily ischemic stroke admission using a two-stage method. Poisson
      time-series regression models were firstly fitted to estimate the effects of air
      pollution in each city. Random-effects meta-analyses were then conducted to
      combine the estimates. Meta-regression models were applied to explore potential
      effect modifiers. More than 2 million hospital admissions for ischemic stroke
      were identified in 172 cities in China. In single-pollutant models, increases of
      10 MUg/m3 in particulate matter with aerodynamic diameter <2.5 MUm (PM2.5),
      sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) and 1 mg/m3 in
      carbon monoxide (CO) concentrations were associated with 0.34% (95% confidence
      interval [CI], 0.20%-0.48%), 1.37% (1.05%-1.70%), 1.82% (1.45%-2.19%), 0.01% (
      0.14%-0.16%), and 3.24% (2.05%-4.43%) increases in hospital admissions for
      ischemic stroke on the same day, respectively. SO2 and NO2 associations remained
      significant in two-pollutant models, but not PM2.5 and CO associations. The
      effect estimates were greater in cities with lower air pollutant levels and
      higher air temperatures, as well as in elderly subgroups. The main limitation of
      the present study was the unavailability of data on individual exposure to
      ambient air pollution. CONCLUSIONS: As the first national study in China to
      systematically examine the associations between short-term exposure to ambient
      air pollution and ischemic stroke, our findings indicate that transient increase
      in air pollution levels may increase the risk of ischemic stroke, which may have
      significant public health implications for the reduction of ischemic stroke
      burden in China.

PMID- 30286079
TI  - GABAergic modulation of olfactomotor transmission in lampreys.
AB  - Odor-guided behaviors, including homing, predator avoidance, or food and mate
      searching, are ubiquitous in animals. It is only recently that the neural
      substrate underlying olfactomotor behaviors in vertebrates was uncovered in
      lampreys. It consists of a neural pathway extending from the medial part of the
      olfactory bulb (medOB) to locomotor control centers in the brainstem via a single
      relay in the caudal diencephalon. This hardwired olfactomotor pathway is present
      throughout life and may be responsible for the olfactory-induced motor behaviors
      seen at all life stages. We investigated modulatory mechanisms acting on this
      pathway by conducting anatomical (tract tracing and immunohistochemistry) and
      physiological (intracellular recordings and calcium imaging) experiments on
      lamprey brain preparations. We show that the GABAergic circuitry of the olfactory
      bulb (OB) acts as a gatekeeper of this hardwired sensorimotor pathway. We also
      demonstrate the presence of a novel olfactomotor pathway that originates in the
      non-medOB and consists of a projection to the lateral pallium (LPal) that, in
      turn, projects to the caudal diencephalon and to the mesencephalic locomotor
      region (MLR). Our results indicate that olfactory inputs can induce behavioral
      responses by activating brain locomotor centers via two distinct pathways that
      are strongly modulated by GABA in the OB. The existence of segregated olfactory
      subsystems in lampreys suggests that the organization of the olfactory system in
      functional clusters may be a common ancestral trait of vertebrates.

PMID- 30286082
TI  - Direct-to-consumer DNA testing of 6,000 dogs reveals 98.6-kb duplication
      associated with blue eyes and heterochromia in Siberian Huskies.
AB  - Consumer genomics enables genetic discovery on an unprecedented scale by linking
      very large databases of personal genomic data with phenotype information
      voluntarily submitted via web-based surveys. These databases are having a
      transformative effect on human genomics research, yielding insights on
      increasingly complex traits, behaviors, and disease by including many thousands
      of individuals in genome-wide association studies (GWAS). The promise of consumer
      genomic data is not limited to human research, however. Genomic tools for dogs
      are readily available, with hundreds of causal Mendelian variants already
      characterized, because selection and breeding have led to dramatic phenotypic
      diversity underlain by a simple genetic structure. Here, we report the results of
      the first consumer genomics study ever conducted in a non-human model: a GWAS of
      blue eyes based on more than 3,000 customer dogs with validation panels including
      nearly 3,000 more, the largest canine GWAS to date. We discovered a novel
      association with blue eyes on chromosome 18 (P = 1.3x10-68) and used both
      sequence coverage and microarray probe intensity data to identify the putative
      causal variant: a 98.6-kb duplication directly upstream of the Homeobox gene
      ALX4, which plays an important role in mammalian eye development. This
      duplication is largely restricted to Siberian Huskies, is strongly associated
      with the blue-eyed phenotype (chi-square P = 5.2x10-290), and is highly, but not
      completely, penetrant. These results underscore the power of consumer-data-driven
      discovery in non-human species, especially dogs, where there is intense owner
      interest in the personal genomic information of their pets, a high level of
      engagement with web-based surveys, and an underlying genetic architecture ideal
      for mapping studies.

PMID- 30286078
TI  - FoxO6 regulates Hippo signaling and growth of the craniofacial complex.
AB  - The mechanisms that regulate post-natal growth of the craniofacial complex and
      that ultimately determine the size and shape of our faces are not well
      understood. Hippo signaling is a general mechanism to control tissue growth and
      organ size, and although it is known that Hippo signaling functions in neural
      crest specification and patterning during embryogenesis and before birth, its
      specific role in postnatal craniofacial growth remains elusive. We have
      identified the transcription factor FoxO6 as an activator of Hippo signaling
      regulating neonatal growth of the face. During late stages of mouse development,
      FoxO6 is expressed specifically in craniofacial tissues and FoxO6-/- mice undergo
      expansion of the face, frontal cortex, olfactory component and skull. Enlargement
      of the mandible and maxilla and lengthening of the incisors in FoxO6-/- mice are
      associated with increases in cell proliferation. In vitro and in vivo studies
      demonstrated that FoxO6 activates Lats1 expression, thereby increasing Yap
      phosphorylation and activation of Hippo signaling. FoxO6-/- mice have
      significantly reduced Hippo Signaling caused by a decrease in Lats1 expression
      and decreases in Shh and Runx2 expression, suggesting that Shh and Runx2 are also
      linked to Hippo signaling. In vitro, FoxO6 activates Hippo reporter constructs
      and regulates cell proliferation. Furthermore PITX2, a regulator of Hippo
      signaling is associated with Axenfeld-Rieger Syndrome causing a flattened midface
      and we show that PITX2 activates FoxO6 expression. Craniofacial specific
      expression of FoxO6 postnatally regulates Hippo signaling and cell proliferation.
      Together, these results identify a FoxO6-Hippo regulatory pathway that controls
      skull growth, odontogenesis and face morphology.

PMID- 30286083
TI  - INDUCER OF CBF EXPRESSION 1 is a male fertility regulator impacting anther
      dehydration in Arabidopsis.
AB  - INDUCER OF CBF EXPRESSION 1 (ICE1) encodes a MYC-like basic helix-loop-helix
      (bHLH) transcription factor playing a critical role in plant responses to
      chilling and freezing stresses and leaf stomata development. However, no
      information connecting ICE1 and reproductive development has been reported. In
      this study, we show that ICE1 controls plant male fertility via impacting anther
      dehydration. The loss-of-function mutation in ICE1 gene in Arabidopsis caused
      anther indehiscence and decreased pollen viability as well as germination rate.
      Further analysis revealed that the anthers in the mutant of ICE1 (ice1-2) had the
      structure of stomium, though the epidermis did not shrink to dehisce. The anther
      indehiscence and influenced pollen viability as well as germination in ice1-2
      were due to abnormal anther dehydration, for most of anthers dehisced with
      drought treatment and pollen grains from those dehydrated anthers had similar
      viability and germination rates compared with wild type. Accordingly, the
      sterility of ice1-2 could be rescued by ambient dehydration treatments. Likewise,
      the stomatal differentiation of ice1-2 anther epidermis was disrupted in a
      different manner compared with that in leaves. ICE1 specifically bound to MYC
      recognition elements in the promoter of FAMA, a key regulator of guard cell
      differentiation, to activate FAMA expression. Transcriptome profiling in the
      anther tissues further exhibited ICE1-modulated genes associated with water
      transport and ion exchange in the anther. Together, this work reveals the key
      role of ICE1 in male fertility control and establishes a regulatory network
      mediated by ICE1 for stomata development and water movement in the anther.

PMID- 30286084
TI  - Population genetic analysis of Chadian Guinea worms reveals that human and non
      human hosts share common parasite populations.
AB  - Following almost 10 years of no reported cases, Guinea worm disease (GWD or
      dracunculiasis) reemerged in Chad in 2010 with peculiar epidemiological patterns
      and unprecedented prevalence of infection among non-human hosts, particularly
      domestic dogs. Since 2014, animal infections with Guinea worms have also been
      observed in the other three countries with endemic transmission (Ethiopia, Mali,
      and South Sudan), causing concern and generating interest in the parasites' true
      taxonomic identity and population genetics. We present the first extensive
      population genetic data for Guinea worm, investigating mitochondrial and
      microsatellite variation in adult female worms from both human and non-human
      hosts in the four endemic countries to elucidate the origins of Chad's current
      outbreak and possible host-specific differences between parasites. Genetic
      diversity of Chadian Guinea worms was considerably higher than that of the other
      three countries, even after controlling for sample size through rarefaction, and
      demographic analyses are consistent with a large, stable parasite population.
      Genealogical analyses eliminate the other three countries as possible sources of
      parasite reintroduction into Chad, and sequence divergence and distribution of
      genetic variation provide no evidence that parasites in human and non-human hosts
      are separate species or maintain isolated transmission cycles. Both among and
      within countries, geographic origin appears to have more influence on parasite
      population structure than host species. Guinea worm infection in non-human hosts
      has been occasionally reported throughout the history of the disease,
      particularly when elimination programs appear to be reaching their end goals.
      However, no previous reports have evaluated molecular support of the parasite
      species identity. Our data confirm that Guinea worms collected from non-human
      hosts in the remaining endemic countries of Africa are Dracunculus medinensis and
      that the same population of worms infects both humans and dogs in Chad. Our
      genetic data and the epidemiological evidence suggest that transmission in the
      Chadian context is currently being maintained by canine hosts.

PMID- 30286086
TI  - Dengue illness index-A tool to characterize the subjective dengue illness
      experience.
AB  - Dengue virus infections are a major cause of febrile illness that significantly
      affects individual and societal productivity and drives up health care costs
      principally in the developing world. Two dengue vaccine candidates are in
      advanced clinical efficacy trials in Latin America and Asia, and another has been
      licensed in more than fifteen countries but its uptake has been limited. Despite
      these advances, standardized metrics for comparability of protective efficacy
      between dengue vaccines remain poorly defined. The Dengue Illness Index (DII) is
      a tool that we developed thru refinement of previous similar iterations in an
      attempt to improve and standardize the measurement of vaccine and drug efficacy
      in reducing moderate dengue illness. The tool is designed to capture an
      individual's overall disease experience based on how the totality of their
      symptoms impacts their general wellness and daily functionality. We applied the
      DII to a diary card, the Dengue Illness Card (DIC), which was examined and
      further developed by a working group. The card was then refined with feedback
      garnered from a Delphi methodology-based query that addressed the adequacy and
      applicability of the tool in clinical dengue research. There was overall
      agreement that the tool would generate useful data and provide an alternative
      perspective to the assessment of drug or vaccine candidates, which in the case of
      vaccines, are assessed by their reduction in any virologically confirmed dengue
      of any severity with a focus on the more severe. The DIC needs to be evaluated in
      the field in the context of vaccine or drug trials, prospective cohort studies,
      or during experimental human infection studies. Here, we present the final DIC
      resulting from the Delphi process and offer its further development or use to the
      dengue research community.

PMID- 30286085
TI  - Development of standard clinical endpoints for use in dengue interventional
      trials.
AB  - Dengue is a major public health problem worldwide. Although several drug
      candidates have been evaluated in randomized controlled trials, none has been
      effective and at present, early recognition of severe dengue and timely
      supportive care are used to reduce mortality. While the first dengue vaccine was
      recently licensed, and several other candidates are in late stage clinical
      trials, future decisions regarding widespread deployment of vaccines and/or
      therapeutics will require evidence of product safety, efficacy and effectiveness.
      Standard, quantifiable clinical endpoints are needed to ensure reproducibility
      and comparability of research findings. To address this need, we established a
      working group of dengue researchers and public health specialists to develop
      standardized endpoints and work towards consensus opinion on those endpoints.
      After discussion at two working group meetings and presentations at international
      conferences, a Delphi methodology-based query was used to finalize and
      operationalize the clinical endpoints. Participants were asked to select the best
      endpoints from proposed definitions or offer revised/new definitions, and to
      indicate whether contributing items should be designated as optional or required.
      After the third round of inquiry, 70% or greater agreement was reached on
      moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis
      and acute liver failure, and moderate and severe neurologic disease. There was
      less agreement regarding moderate and severe thrombocytopenia and moderate and
      severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000
      mm3 platelet range be used to define moderate thrombocytopenia; however, they
      remained divided on whether a rapid decreasing trend or one platelet count should
      be case defining. While at least 70% agreement was reached on most endpoints, the
      process identified areas for further evaluation and standardization within the
      context of ongoing clinical studies. These endpoints can be used to harmonize
      data collection and improve comparability between dengue clinical trials.

PMID- 30286087
TI  - Human immunodeficiency virus status in malnourished children seen at Lagos.
AB  - INTRODUCTION: Human immunodeficiency virus and protein energy malnutrition are
      still prevalent in Nigeria and the occurrence of the two conditions together
      confers a poor prognosis. The aim of this study was to determine the current
      categories of malnutrition amongst under-5 children in Lagos, document their HIV
      status and determine any peculiarities in the clinical features, haematological
      and some biochemical profile in these children. METHODS: The study was a cross
      sectional study conducted at the Paediatric departments of the Lagos University
      Teaching Hospital and the Massey Street Children's Hospital, both in Lagos, over
      a 6-month period. All the subjects had anthropometry, HIV testing, full blood
      count and serum proteins done. The factors associated with HIV status were
      determined with the logistic regression analysis. RESULTS: Two hundred and
      fourteen (214) malnourished children <=5 years, including 25 (11.7%) with HIV
      were recruited in the study. Among the study participants, 150 (70.1%) and 54
      (29.9%) had moderate and severe malnutrition, respectively. Fever, cough and
      diarrhea were the most common symptoms in the study participants. The
      haematological indices were comparable in the two groups, the serum globulin
      levels though higher in the HIV infected group was not statistically
      significantly different from the non-infected group.(p = 0.66). None of the
      factors explored on multivariate analysis was able to predict the occurrence of
      the infection in this cohort. CONCLUSION: Malnourished children remain a high
      risk group for HIV infection and the prevalence of the infection obtained in this
      group of children is still unacceptably high. Discriminatory features between
      malnutrition and HIV remains difficult. The presence of hyperglobulinaemia on
      laboratory analysis in a malnourished child may heighten the suspicion of
      possible underlying associated HIV infection. Screening of malnourished children
      for HIV infection and further longitudinal studies on malnourished children with
      HIV is advocated.

PMID- 30286088
TI  - Integrated analysis of DNA methylation profiling and gene expression profiling
      identifies novel markers in lung cancer in Xuanwei, China.
AB  - BACKGROUND: Aberrant DNA methylation occurs frequently in cancer. The aim of this
      study was to identify novel methylation markers in lung cancer in Xuanwei, China,
      through integrated genome-wide DNA methylation and gene expression studies.
      METHODS: Differentially methylated regions (DMRs) and differentially expressed
      genes (DEGs) were detected on 10 paired lung cancer tissues and noncancerous lung
      tissues by methylated DNA immunoprecipitation combined with microarray (MeDIP
      chip) and gene expression microarray analyses, respectively. Integrated analysis
      of DMRs and DEGs was performed to screen out candidate methylation-related genes.
      Both methylation and expression changes of the candidate genes were further
      validated and analyzed. RESULTS: Compared with normal lung tissues, lung cancer
      tissues expressed a total of 6,899 DMRs, including 5,788 hypermethylated regions
      and 1,111 hypomethylated regions. Integrated analysis of DMRs and DEGs identified
      45 tumor-specific candidate genes: 38 genes whose DMRs were hypermethylated and
      expression was downregulated, and 7 genes whose DMRs were hypomethylated and
      expression was upregulated. The methylation and expression validation results
      identified 4 candidate genes (STXBP6, BCL6B, FZD10, and HSPB6) that were
      significantly hypermethylated and downregulated in most of the tumor tissues
      compared with the noncancerous lung tissues. CONCLUSIONS: This integrated
      analysis of genome-wide DNA methylation and gene expression in lung cancer in
      Xuanwei revealed several genes regulated by promoter methylation that have not
      been described in lung cancer before. These results provide new insight into the
      carcinogenesis of lung cancer in Xuanwei and represent promising new diagnostic
      and therapeutic targets.

PMID- 30286089
TI  - Mitigating the impact of microbial pressure on great (Parus major) and blue
      (Cyanistes caeruleus) tit hatching success through maternal immune investment.
AB  - The hatching success of a bird's egg is one of the key determinants of avian
      reproductive success, which may be compromised by microbial infections causing
      embryonic death. During incubation, outer eggshell bacterial communities pose a
      constant threat of pathogen translocation and embryo infection. One of the
      parental strategies to mitigate this threat is the incorporation of maternal
      immune factors into the egg albumen and yolk. It has been suggested that habitat
      changes like forest fragmentation can affect environmental factors and life
      history traits that are linked to egg contamination. This study aims at
      investigating relationships between microbial pressure, immune investment and
      hatching success in two abundant forest bird species and analyzing to what extent
      these are driven by extrinsic (environmental) factors. We here compared (1) the
      bacterial load and composition on eggshells, (2) the level of immune defenses in
      eggs, and (3) the reproductive success between great (Parus major) and blue
      (Cyanistes caeruleus) tits in Belgium and examined if forest fragmentation
      affects these parameters. Analysis of 70 great tit and 34 blue tit eggshells
      revealed a similar microbiota composition (Enterobacteriaceae, Lactobacillus
      spp., Firmicutes and Bacteroidetes), but higher bacterial loads in great tits.
      Forest fragmentation was not identified as an important explanatory variable.
      Although a significant negative correlation between hatching success and
      bacterial load on the eggshells in great tits corroborates microbial pressure to
      be a driver of embryonic mortality, the overall hatching success was only
      marginally lower than in blue tits. This may be explained by the significantly
      higher levels of lysozyme and IgY in the eggs of great tits, protecting the
      embryo from increased infection pressure. Our results show that immune investment
      in eggs is suggested to be a species-specific adaptive trait that serves to
      protect hatchlings from pathogen pressure, which is not directly linked to
      habitat fragmentation.

PMID- 30286090
TI  - Gender and household structure factors associated with maternal and child
      undernutrition in rural communities in Ethiopia.
AB  - Addressing maternal and child undernutrition is a priority for the National
      Nutrition Program of Ethiopia. In a cross-sectional design, we selected mother
      child pairs (n = 630) from Halaba, south Ethiopia (n = 413, two communities) and
      Zeway, Oromiya region (n = 217, one community). These communities were previously
      included in a project to improve agricultural practices. We aimed to estimate the
      level of maternal and child undernutrition in the two study sites and compare
      findings to regional/national reports. We also examined associations with gender,
      household-structure and nutrition/health related variables. Households were
      selected using simple random sampling based on list of households obtained from
      local health posts. Mothers were interviewed via questionnaire. Anthropometric
      measurements were taken from mothers-child pairs. Maternal undernutrition (%
      BMI<18.5) ranged from moderate (14% Zeway) to high (22% Halaba). In the children,
      stunting and underweight were very high (54% and 42% stunting, 36% and 21%
      underweight, in Halaba and Zeway, respectively). Up to 95% of Halaba and 85% of
      Zeway mothers reported "same as usual" or "less than usual" consumption patterns
      during their most recent pregnancy compared to periods of non-pregnancy. Mothers
      reported (61% in Halaba, 18% in Zeway) abstaining from consumption of certain
      nutritious foods for cultural reasons. Gender and socio-economic-demographic
      structure of the households, including imbalance of power, control of farm
      produce, physiological density, household size and dietary habits during
      pregnancy showed significant associations with maternal and child undernutrition
      (p<0.05). The levels of child and maternal undernutrition, particularly in
      children, were unexpected and of concern, given that a national nutrition program
      has been in place since 2008. The study provides insights for policy makers to
      improve women's education, reproductive health services for better family
      planning, and strengthen nutrition/health programs designed to target vulnerable
      segments of the population in these and other rural communities and districts
      with similar structure and demographics in Ethiopia.

PMID- 30286092
TI  - Representation effects in the centipede game.
AB  - We explore the effects on strategic behavior of alternative representations of a
      centipede game that differ in terms of complexity. In a laboratory experiment, we
      manipulate the way in which payoffs are presented to subjects in two different
      ways. In both cases, information is made less accessible relative to the standard
      representation of the game. Results show that these manipulations shift the
      distribution of take nodes further away from the equilibrium prediction. The
      evidence is consistent with the view that failures of game-form recognition and
      the resulting limits to strategic reasoning are crucial for explaining non
      equilibrium behavior in the centipede game.

PMID- 30286091
TI  - Feedbacks from the metabolic network to the genetic network reveal regulatory
      modules in E. coli and B. subtilis.
AB  - The genetic regulatory network (GRN) plays a key role in controlling the response
      of the cell to changes in the environment. Although the structure of GRNs has
      been the subject of many studies, their large scale structure in the light of
      feedbacks from the metabolic network (MN) has received relatively little
      attention. Here we study the causal structure of the GRNs, namely the chain of
      influence of one component on the other, taking into account feedback from the
      MN. First we consider the GRNs of E. coli and B. subtilis without feedback from
      MN and illustrate their causal structure. Next we augment the GRNs with feedback
      from their respective MNs by including (a) links from genes coding for enzymes to
      metabolites produced or consumed in reactions catalyzed by those enzymes and (b)
      links from metabolites to genes coding for transcription factors whose
      transcriptional activity the metabolites alter by binding to them. We find that
      the inclusion of feedback from MN into GRN significantly affects its causal
      structure, in particular the number of levels and relative positions of nodes in
      the hierarchy, and the number and size of the strongly connected components
      (SCCs). We then study the functional significance of the SCCs. For this we
      identify condition specific feedbacks from the MN into the GRN by retaining only
      those enzymes that are essential for growth in specific environmental conditions
      simulated via the technique of flux balance analysis (FBA). We find that the SCCs
      of the GRN augmented by these feedbacks can be ascribed specific functional roles
      in the organism. Our algorithmic approach thus reveals relatively autonomous
      subsystems with specific functionality, or regulatory modules in the organism.
      This automated approach could be useful in identifying biologically relevant
      modules in other organisms for which network data is available, but whose biology
      is less well studied.

PMID- 30286093
TI  - High-fat diet suppresses the positive effect of creatine supplementation on
      skeletal muscle function by reducing protein expression of IGF-PI3K-AKT-mTOR
      pathway.
AB  - High-fat (HF) diets in combination with sedentary lifestyle represent one of the
      major public health concerns predisposing to obesity and diabetes leading to
      skeletal muscle atrophy, decreased fiber diameter and muscle mass with
      accumulation of fat tissue resulting in loss of muscle strength. One strategy to
      overcome the maleficent effects of HF diet is resistance training, a strategy
      used to improve muscle mass, reverting the negative effects on obesity-related
      changes in skeletal muscle. Together with resistance training, supplementation
      with creatine monohydrate (CrM) in the diet has been used to improve muscle mass
      and strength. Creatine is a non-essential amino acid that is directly involved in
      the cross-bridge cycle providing a phosphate group to ADP during the initiation
      of muscle contraction. Besides its antioxidant and anti-inflammatory effects CrM
      also upregulates IGF-1 resulting in hyperthophy with an increase in muscle
      function. However, it is unknown whether CrM supplementation during resistance
      training would revert the negative effects of high-fat diet on the muscle
      performance. During 8 weeks we measured muscle performance to climb a 1.1m and 80
      degrees  ladder with increasing load on trained rats that had received standard
      diet or high-fat diet, supplemented or not with CrM. We observed that the CrM
      supplementation up-regulated IGF-1 and phospho-AKT protein levels, suggesting an
      activation of the IGF1-PI3K-Akt/PKB-mTOR pathway. Moreover, despite the CrM
      supplementation, HF diet down-regulated several proteins of the IGF1-PI3K-Akt/PKB
      mTOR pathway, suggesting that diet lipid content is crucial to maintain or
      improve muscle function during resistance training.

PMID- 30286094
TI  - Assessing the pedestrian response to urban outdoor lighting: A full-scale
      laboratory study.
AB  - This study identifies and applies methods for evaluating the human response to
      pedestrian lighting applications intended for future use by the municipality of
      Malmo, Sweden. The methods employed provide a supplementary perspective to that
      given by the photometric properties of the lighting applications. The study
      involved 89 participants from two age groups (Young: N: 43, 19-31 yrs.; Elderly:
      N: 46, 62-77 yrs.). Data were collected in a full-scale laboratory using a mock
      up pedestrian pathway. Three lighting applications (one ceramic metal halide and
      two LED) were presented and the participants' behavior (walking speed),
      perception (ability to perform visual tasks-recognize facial expressions, detect
      obstacles, read street signpost), affective response, and evaluation of the
      lighting quality were assessed. The three lighting applications significantly
      differed with regard to the human response. The facial expression recognition
      distance, sign reading distance and the obstacle detection task, along with the
      evaluation of lighting quality and level of arousal, distinguished one of the
      LEDs (Correlated Color Temperature: 3810, Color Rendering Index: 75,
      Scotopic/Photopic ratio: 1.48) from the other two lighting applications-the
      participants performed better on the visual tasks, and the lighting was perceived
      as brighter, more arousing and less pleasant. Methods to capture human
      perception, evaluation and behavior in relation to outdoor lighting, provide a
      valuable perspective that should be systematically applied when municipalities
      consider different pedestrian lighting applications.

PMID- 30286095
TI  - Inter- and intra-host sequence diversity reveal the emergence of viral variants
      during an overwintering epidemic caused by dengue virus serotype 2 in southern
      Taiwan.
AB  - Purifying selection during dengue viral infection has been suggested as the
      driving force of viral evolution and the higher complexity of the intra-host
      quasi-species is thought to offer an adaptive advantage for arboviruses as they
      cycle between arthropod and vertebrate hosts. However, very few studies have been
      performed to investigate the viral genetic changes within (intra-host) and
      between (inter-host) humans in a spatio-temporal scale. Viruses of different
      serotypes from various countries imported to Taiwan cause annual outbreaks.
      During 2001-2003, two consecutive outbreaks were caused by dengue virus serotype
      2 (DENV-2) and resulted in a larger-scale epidemic with more severe dengue cases
      in the following year. Phylogenetic analyses showed that the viruses from both
      events were similar and related to the 2001 DENV-2 isolate from the Philippines.
      We comprehensively analyzed viral sequences from representative dengue patients
      and identified three consensus genetic variants, group Ia, Ib and II, with
      different spatio-temporal population dynamics. The phylodynamic analysis
      suggested group Ib variants, characterized by lower genetic diversity,
      transmission rate, and intra-host variant numbers, might play the role of
      maintenance variants. The residential locations among the patients infected by
      group Ib variants were in the outer rim of case clusters throughout the 2001-2003
      period whereas group Ia and II variants were located in the centers of case
      clusters, suggesting that group Ib viruses might serve as "sheltered
      overwintering" variants in an undefined ecological niche. Further deep sequencing
      of the viral envelope (E) gene directly from individual patient serum samples
      confirmed the emergence of variants belonging to three quasi-species (group Ia,
      Ib, and II) and the ancestral role of the viral variants in the latter phase of
      the 2001 outbreak contributed to the later, larger-scale epidemic beginning in
      2002. These findings enhanced our understanding of increasing epidemic severity
      over time in the same epidemic area. It also highlights the importance of
      combining phylodynamic and deep sequencing analysis as surveillance tools for
      detecting dynamic changes in viral variants, particularly searching for and
      monitoring any specific viral subpopulation. Such subpopulations might have
      selection advantages in both fitness and transmissibility leading to increased
      epidemic severity.

PMID- 30286096
TI  - Profiling of circulating exosomal miRNAs in patients with Waldenstrom
      Macroglobulinemia.
AB  - Waldenstrom Macroglobulinemia (WM) is a low-grade B-cell lymphoma characterized
      by disease progression from IgM MGUS to asymptomatic and then symptomatic disease
      states. We profiled exosomes from the peripheral blood of patients with WM at
      different stages (30 smoldering/asymptomatic WM, 44 symptomatic WM samples and 10
      healthy controls) to define their role as potential biomarkers of disease
      progression. In this study, we showed that circulating exosomes and their miRNA
      content represent unique markers of the tumor and its microenvironment. We
      observed similar levels of miRNAs in exosomes from patients with asymptomatic
      (smoldering) and symptomatic WM, suggesting that environmental and clonal changes
      occur in patients at early stages of disease progression before symptoms occur.
      Moreover, we identified a small group of miRNAs whose expression correlated
      directly or inversely with the disease status of patients, notably the known
      tumor suppressor miRNAs let-7d and the oncogene miR-21 as well as miR-192 and miR
      320b. The study of these miRNAs' specific effect in WM cells could help us gain
      further insights on the mechanisms underlying WM pathogenesis and reveal their
      potential as novel therapeutic targets for this disease.

PMID- 30286097
TI  - Deep learning in chest radiography: Detection of findings and presence of change.
AB  - BACKGROUND: Deep learning (DL) based solutions have been proposed for
      interpretation of several imaging modalities including radiography, CT, and MR.
      For chest radiographs, DL algorithms have found success in the evaluation of
      abnormalities such as lung nodules, pulmonary tuberculosis, cystic fibrosis,
      pneumoconiosis, and location of peripherally inserted central catheters. Chest
      radiography represents the most commonly performed radiological test for a
      multitude of non-emergent and emergent clinical indications. This study aims to
      assess accuracy of deep learning (DL) algorithm for detection of abnormalities on
      routine frontal chest radiographs (CXR), and assessment of stability or change in
      findings over serial radiographs. METHODS AND FINDINGS: We processed 874 de
      identified frontal CXR from 724 adult patients (> 18 years) with DL (Qure AI).
      Scores and prediction statistics from DL were generated and recorded for the
      presence of pulmonary opacities, pleural effusions, hilar prominence, and
      enlarged cardiac silhouette. To establish a standard of reference (SOR), two
      thoracic radiologists assessed all CXR for these abnormalities. Four other
      radiologists (test radiologists), unaware of SOR and DL findings, independently
      assessed the presence of radiographic abnormalities. A total 724 radiographs were
      assessed for detection of findings. A subset of 150 radiographs with follow up
      examinations was used to asses change over time. Data were analyzed with receiver
      operating characteristics analyses and post-hoc power analysis. RESULTS: About
      42% (305/ 724) CXR had no findings according to SOR; single and multiple
      abnormalities were seen in 23% (168/724) and 35% (251/724) of CXR. There was no
      statistical difference between DL and SOR for all abnormalities (p = 0.2-0.8).
      The area under the curve (AUC) for DL and test radiologists ranged between 0.837
      0.929 and 0.693-0.923, respectively. DL had lowest AUC (0.758) for assessing
      changes in pulmonary opacities over follow up CXR. Presence of chest wall
      implanted devices negatively affected the accuracy of DL algorithm for evaluation
      of pulmonary and hilar abnormalities. CONCLUSIONS: DL algorithm can aid in
      interpretation of CXR findings and their stability over follow up CXR. However,
      in its present version, it is unlikely to replace radiologists due to its limited
      specificity for categorizing specific findings.

PMID- 30286098
TI  - Identification of a VapA virulence factor functional homolog in Rhodococcus equi
      isolates housing the pVAPB plasmid.
AB  - Rhodococcus equi is a facultative intracellular bacterium of macrophages and is
      an important pathogen of animals and immunocompromised people wherein disease
      results in abcessation of the lungs and other sites. Prior work has shown that
      the presence of the major virulence determinant, VapA, encoded on the pVAPA-type
      plasmid, disrupts normal phagosome development and is essential for bacterial
      replication within macrophages. pVAPA- type plasmids are typical of R. equi
      strains derived from foals while strains from pigs carry plasmids of the pVAPB
      type, lacking vapA, and those from humans harbor various types of plasmids
      including pVAPA and pVAPB. Through the creation and analysis of a series of gene
      deletion mutants, we found that vapK1 or vapK2 is required for optimal
      intracellular replication of an R. equi isolate carrying a pVAPB plasmid type.
      Complementation analysis of a DeltavapA R. equi strain with vapK1 or vapK2 showed
      the VapK proteins of the pVAPB-type plasmid could restore replication capacity to
      the macrophage growth-attenuated DeltavapA strain. Additionally, in contrast to
      the intracellular growth capabilities displayed by an equine R. equi
      transconjugant strain carrying a pVAPB-type plasmid, a transconjugant strain
      carrying a pVAPB-type plasmid deleted of vapK1 and vapK2 proved incapable of
      replication in equine macrophages. Cumulatively, these data indicate that VapK1
      and K2 are functionally equivalent to VapA.

PMID- 30286100
TI  - Ten simple rules when considering retirement.

PMID- 30286101
TI  - Performance appraisal method for rural infrastructure construction based on
      public satisfaction.
AB  - Rural infrastructure has rather fixed users compared to urban infrastructure.
      This study evaluated the effect of rural infrastructure construction from the
      perspective of farmers. First, this study revised the American Customer
      Satisfaction Index (ACSI) model and selected a performance appraisal index for
      rural infrastructure based on this revised model. Then, the study adopted an
      interpretive structural model (ISM), analyzed the influence of each index factor,
      and developed a hierarchical directed graph. Finally, based on the mutual
      influence relationships among the index factors in the hierarchical directed
      graph, a performance appraisal analytic network process (ANP) model was
      established. Based on discussions with rural college students and rural
      households in Sichuan, China, 246 questionnaires were obtained pertaining to
      rural infrastructure, and an empirical analysis was conducted. The results
      indicated that the performance of rural infrastructure construction is not very
      good. In particular, the full use of infrastructure and its role in improving the
      environment were found to be the worst. Meanwhile, the possibility of building
      information transparency and the longitudinal comparison of perceived performance
      appraisal results were the best. The performance of rural infrastructure
      construction was evaluated based on the perceptions of the direct users of rural
      infrastructure, and the relationship between the factors and the weight was
      measured reasonably. The proposed method was found to be workable and the
      analysis results reliable and effective.

PMID- 30286099
TI  - Assessment of inner and outer retinal layer metrics on the Cirrus HD-OCT Platform
      in normal eyes.
AB  - PURPOSE: Ellipsoid zone (EZ) and outer retinal integrity are strongly linked to
      visual prognosis, but quantitative normative data is lacking. This study
      evaluates the EZ, outer retina, and inner retina in eyes without macular disease
      across a wide age spectrum. METHODS: An IRB-approved study was performed for eyes
      without macular pathology undergoing Spectral Domain Optical Coherence Tomography
      (SD-OCT) scans on the Cirrus HD-OCT system (Carl Zeiss Meditec, Oberkochen,
      Germany). Scans were analyzed using a previously described automated EZ mapping
      tool with line-by-line manual verification. Segmentation included internal
      limiting membrane (ILM), outer nuclear layer/Henle fiber layer complex (ONL/HFL),
      EZ, and the retinal pigment epithelium (RPE). The output included metrics for the
      inner retina (ILM-OPL/HFL), outer retina (ONL/HFL-RPE), EZ-RPE area and volume,
      and en face EZ mapping. EZ-RPE attenuation on en face mapping was defined as EZ
      RPE thickness < 20 um, and total attenuation was 0 um. Imaging parameters were
      assessed for the group and compared to age, sex, visual acuity and spherical
      equivalent. RESULTS: 167 eyes from 167 subjects were included. Mean age was 49.7
      years (range 10-84 years). The mean foveal retinal thickness was 200.58 +/- 19.22
      um. Mean inner retinal thickness was 21.47 +/- 13.60 um. Mean outer retinal
      thickness was 179.11 +/- 18.52 um. Mean EZ-RPE thickness was 50.58 +/- 6.01um.
      The mean EZ-RPE volume was 1.20 +/- 0.10 mm3. Mean EZ attenuation percentage per
      macular map area was 0.87% +/- 1.13% and mean percentage total attenuation was
      0.12% +/- 0.14%. Total and inner retinal thickness metrics decreased with age.
      Mean outer retinal thickness increased with age. EZ-RPE parameters were unchanged
      with age. However, EZ attenuation was negatively correlated with age. CONCLUSION:
      This study provides important information for inner and outer retinal parameters.
      Future research on quantitative EZ integrity can utilize this data for
      comparison.

PMID- 30286102
TI  - Evolution of urban scaling: Evidence from Brazil.
AB  - During the last years, the new science of cities has been established as a
      fertile quantitative approach to systematically understand the urban phenomena.
      One of its main pillars is the proposition that urban systems display universal
      scaling behavior regarding socioeconomic, infrastructural and individual basic
      services variables. This paper discusses the extension of the universality
      proposition by testing it against a broad range of urban metrics in a developing
      country urban system. We present an exploration of the scaling exponents for over
      60 variables for the Brazilian urban system. Estimating those exponents is
      challenging from the technical point of view because the Brazilian
      municipalities' definition follows local political criteria and does not regard
      characteristics of the landscape, density, and basic utilities. As Brazilian
      municipalities can deviate significantly from urban settlements, urban-like
      municipalities were selected based on a systematic density cut-off procedure and
      the scaling exponents were estimated for this new subset of municipalities. To
      validate our findings we compared the results for overlaying variables with other
      studies based on alternative methods. It was found that the analyzed
      socioeconomic variables follow a superlinear scaling relationship with the
      population size, and most of the infrastructure and individual basic services
      variables follow expected sublinear and linear scaling, respectively. However,
      some infrastructural and individual basic services variables deviated from their
      expected regimes, challenging the universality hypothesis of urban scaling. We
      propose that these deviations are a product of top-down decisions/policies. Our
      analysis spreads over a time-range of 10 years, what is not enough to draw
      conclusive observations, nevertheless we found hints that the scaling exponent of
      these variables are evolving towards the expected scaling regime, indicating that
      the deviations might be temporally constrained and that the urban systems might
      eventually reach the expected scaling regime.

PMID- 30286103
TI  - Is there such a thing as a 'lope' dope? Analysis of loperamide-related European
      Medicines Agency (EMA) pharmacovigilance database reports.
AB  - BACKGROUND: Among over-the-counter (OTC) drugs, loperamide has recently emerged
      for its potential of misuse and cardiotoxicity issues. Hence, we aimed here at
      assessing the loperamide-related cases being reported to the EMA's EudraVigilance
      (EV) database. METHODS: All spontaneous EV reports relating to loperamide
      misuse/abuse/dependence/withdrawal and cardiotoxicity issues were here retrieved,
      performing a descriptive analysis. FINDINGS: During the years 2005-2017, EV
      collected a number of 1,983 (out of a total of 7,895; 25.11%) loperamide-related
      misuse/abuse/dependence/withdrawal adverse drug reaction (ADR) reports, with a
      progressively increasing trend since 2014. Most cases were classified as drug use
      disorder (37.4%) or intentional overdose (25.4%). Loperamide was used on its own
      in 41.9% of cases; remaining, polydrug, cases included antidepressants;
      benzodiazepines; and other OTCs. Some 1,085 (1,085/7,895 = 13.7%) cardiovascular
      ADRs were reported, being conduction abnormalities and EKG alterations the most
      frequently identified. CONCLUSIONS: EV data may support the levels of concern
      relating to loperamide potential of abuse and associated cardiotoxicity issues.

PMID- 30286104
TI  - Contextual work design and employee innovative work behavior: When does autonomy
      matter?
AB  - In environments experiencing fast technological change in which innovative
      performance is expected, work design research has found that the degree of
      autonomy positively predicts behavioral and attitudinal work outcomes. Because
      extant work design research has tended to examine the direct and mediating
      effects of autonomy on work outcomes such as job satisfaction, examinations of
      more situational elements and the degree to which the organizational context
      strengthens or weakens this relationship has been neglected. This study,
      therefore, takes a context-contingent perspective to investigate the degree to
      which psychological climate dimensions such as supervisor support, organizational
      structure and organizational innovation moderate the effects of autonomy (work
      scheduling autonomy, work methods autonomy, decision-making autonomy) on employee
      perceived innovative work behavior (IWB). Using a conjoint experiment based on
      9,440 assessments nested within 1,180 employees, it was found that all autonomy
      dimensions had a significant direct effect on employee perceived IWB. Contrary to
      the Hypotheses, the multi-level analysis did not reveal any moderating effect of
      the climate dimensions on the relationship between autonomy and employee IWB.
      This study provides a context-contingent view for the features of work design and
      gives a more detailed analysis of autonomy, which has previously been seen
      primarily as a unidimensional construct.

PMID- 30286105
TI  - Assessment and agreement of the CT appearance pattern and its severity grading of
      radiation-induced lung injury after stereotactic body radiotherapy for lung
      cancer.
AB  - PURPOSE: Radiographic severity of radiation-induced lung injury (RILI) has not
      been well-studied. The goal of this study was to assess the CT appearance pattern
      and severity of RILI without consideration of the clinical presentation. MATERIAL
      AND METHODS: A total of 49 patients, 41 with primary lung cancer and 8 with
      metastatic lung cancer, were treated by 4-fraction stereotactic body radiotherapy
      (SBRT). RILI after SBRT was separately assessed by two observers. The early and
      late CT appearance patterns and CT-based severity grading were explored. RESULTS:
      The median follow-up period was 39.0 months. In the early CT findings of
      observers 1 and 2, there was diffuse consolidation in 15 and 8, diffuse ground
      glass opacity (GGO) in 0 and 0, patchy consolidation and GGO in 17 and 20, patchy
      GGO in 3 and 3, and no changes in 10 and 14, respectively (kappa = 0.61). In late
      CT findings of observer 1 and 2, there were modified conventional pattern in 28
      and 24, mass-like pattern in 8 and 11, scar-like pattern in 12 and 12, and no
      changes in 1 and 2, respectively (kappa = 0.63). In the results of the CT-based
      grading by observers 1 and 2, there were grade 0 in 1 and 2, grade 1 in 10 and
      14, grade 2 in 31 and 29, grade 3 in 7 and 4, and none of grade 4 or more,
      respectively (kappa = 0.66). According to multivariate analyses (MVA), the
      significant predicting factors of grade 2 or more CT-based RILI were age (p =
      0.01), oxygen dependence (p = 0.03) and interstitial shadow (p = 0.03).
      CONCLUSIONS: The agreement of the CT appearance and CT-based grading between two
      observers was good. These indicators may be able to provide us with more
      objective information and a better understanding of RILI.

PMID- 30286106
TI  - The clinical relevance of ABO blood type in 100 patients with acute subdural
      hematoma.
AB  - OBJECTIVE: The correlation of depleted blood through midline shift in acute
      subdural hematoma remains the most reliable clinical predictor to date. On the
      other hand, patient's ABO blood type has a profound impact on coagulation and
      hemostasis. We conducted this study to evaluate the role of patient's blood type
      in terms of incidence, clinical course and outcome after acute subdural hematoma
      bleeding. METHODS: 100 patients with acute subdural hematoma treated between 2010
      and 2015 at the author's institution were included. Baseline characteristics and
      clinical findings including Glasgow coma scale, Glasgow outcome scale, hematoma
      volume, rebleeding, midline shift, postoperative seizures and the presence of
      anticoagulation were analyzed for their association with ABO blood type. RESULTS:
      Patient's with blood type O were found to have a lower midline shift (p<0.01) and
      significantly less seizures (OR: 0.43; p<0.05) compared to non-O patients.
      Furthermore, patients with blood type A had the a significantly higher midline
      shift (p<0.05) and a significantly increased risk for postoperative seizures (OR:
      4.01; p<0.001). There was no difference in ABO blood type distribution between
      acute subdural hematoma patients and the average population. CONCLUSION: The ABO
      blood type has significant influence on acute subdural hematoma sequelae.
      Patient's with blood type O benefit in their clinical course after acute subdural
      hematoma whereas blood type A patients are at highest risk for increased midline
      shift and postoperative seizures. Further studies elucidating the biological
      mechanisms of blood type depended hemostaseology and its role in acute subdural
      hematoma are required for the development of an appropriate intervention.

PMID- 30286107
TI  - RankProt: A multi criteria-ranking platform to attain protein thermostabilizing
      mutations and its in vitro applications - Attribute based prediction method on
      the principles of Analytical Hierarchical Process.
AB  - Attaining recombinant thermostable proteins is still a challenge for protein
      engineering. The complexity is the length of time and enormous efforts required
      to achieve the desired results. Present work proposes a novel and economic
      strategy of attaining protein thermostability by predicting site-specific
      mutations at the shortest possible time. The success of the approach can be
      attributed to Analytical Hierarchical Process and the outcome was a rationalized
      thermostable mutation(s) prediction tool- RankProt. Briefly the method involved
      ranking of 17 biophysical protein features as class predictors, derived from 127
      pairs of thermostable and mesostable proteins. Among the 17 predictors, ionic
      interactions and main-chain to main-chain hydrogen bonds were the highest ranked
      features with eigen value of 0.091. The success of the tool was judged by multi
      fold in silico validation tests and it achieved the prediction accuracy of 91%
      with AUC 0.927. Further, in vitro validation was carried out by predicting
      thermostabilizing mutations for mesostable Bacillus subtilis lipase and
      performing the predicted mutations by multi-site directed mutagenesis. The
      rationalized method was successful to render the lipase thermostable with optimum
      temperature stability and Tm increase by 20 degrees C and 7 degrees C
      respectively. Conclusively it can be said that it was the minimum number of
      mutations in comparison to the number of mutations incorporated to render
      Bacillus subtilis lipase thermostable, by directed evolution techniques. The
      present work shows that protein stabilizing mutations can be rationally designed
      by balancing the biophysical pleiotropy of proteins, in accordance to the
      selection pressure.

PMID- 30286108
TI  - Factors predicting the therapeutic response to infliximab during maintenance
      therapy in Japanese patients with Crohn's disease.
AB  - Since anti-tumor necrosis factor (TNF)-alpha agents (TNF-alpha inhibitors) induce
      both clinical response and remission in patients with moderate to severe
      inflammatory bowel disease (IBD), the use of anti-TNF therapies has fundamentally
      changed the approach to treatment for patients with IBD. Infliximab (IFX) is a
      TNF-alpha inhibitor approved for the induction and remission of Crohn's disease
      (CD). However, even among patients who initially demonstrate a clinical response
      to IFX therapy, secondary loss of response occurs, although the reason remains
      unknown. We therefore investigated predictive factors associated with the
      response to IFX in long-term maintenance treatment in Japanese CD patients. Eight
      types of single-nucleotide polymorphisms (SNPs) were investigated using the real
      time PCR method, and patient characteristics were collected from the electronic
      medical records. The Crohn's Disease Activity Index criteria were used as the
      response to IFX therapy. The observation period was 1 year after IFX had been
      administered for more than 1 year. Associations between the IFX response and
      patient characteristics were evaluated using the multivariate logistic regression
      model. We studied 121 unrelated adult Japanese with CD treated for more than 1
      year with IFX as outpatients at Keio University Hospital from November 1, 2014 to
      November 30, 2015. Among them, 71 were classified as in remisson. In multivariate
      analysis, patients with the TNF-alpha 857C>T C/C genotype, shorter disease
      duration, without double dosing, and combination treatment with an
      immunomodulator had higher remisson rates than those with the C/T or T/T
      genotype, longer disease duration, with double dosing, and no combination
      treatment with an immunomodulator. The response to IFX in Japanese CD patients
      may therefore be predicted by these 4 characteristics in actual clinical
      practice.

PMID- 30286109
TI  - A theoretical insight to understand the molecular mechanism of dual target ligand
      CTA-018 in the chronic kidney disease pathogenesis.
AB  - The level of the vitamin D in the bloodstream is regulated by cytochrome P450
      enzyme 24-hydroxylase A1 (CYP24A1). Over expression of CYP24A1 enzyme is
      correlated with vitamin D deficiency and resistance to vitamin D therapy. Chronic
      kidney disease (CKD) patients are commonly reported with the above said
      expression variations. This deregulation could be solved by ligands that act as a
      vitamin D receptor (VDR) agonists and CYP24A1 antagonists. Posner et al., (2010)
      first time reported two new vitamin D analogues namely CTA-091 and CTA-018 to
      inhibit CYP24A1. The CTA-018 inhibited CYP24A1 with an IC50 27 +/- 6 nM (10 times
      more potent than the ketoconazole (253 +/- 20 nM)). CTA-018 induced VDR
      expression (15-fold lower than 1alpha,25(OH)2D3) and is under phase II clinical
      trial, whereas CTA-091 was not able to efficiently induce the VDR expression
      (>2000 nM). To explore the molecular mechanism, binding specificity of these two
      vitamin D analogues along with native ligand was extensively studied through in
      silico approaches. Through molecular dynamics simulations studies, we shown that
      the sulfonic group (O = S = O) in the side chain of CTA-018 plays an important
      role in the regulation of VDR agonistic activity. The electron lone pairs of the
      sulfonic group that interacted with His393 lead to be a factor for agonistic
      mechanism of VDR activity. Compared to azol-based compounds, CTA-018 binds the
      different sites in the CYP24A1 binding cavity and thus it could be a potent
      antagonistic for CYP24A1enzyme.

PMID- 30286110
TI  - Non-invasive evaluation of neurovascular coupling in the murine retina by dynamic
      retinal vessel analysis.
AB  - BACKGROUND: Impairment of neurovascular coupling (NVC) was recently reported in
      the context of subarachnoid hemorrhage and may correlate with disease severity
      and outcome. However, previous techniques to evaluate NVC required invasive
      procedures. Retinal vessels may represent an alternative option for non-invasive
      assessment of NVC. METHODS: A prototype of an adapted retinal vessel analyzer was
      used to assess retinal vessel diameter in mice. Dynamic vessel analysis (DVA)
      included an application of monochromatic flicker light impulses in predefined
      frequencies for evaluating NVC. All retinae were harvested after DVA and
      electroretinograms were performed. RESULTS: A total of 104 retinal scans were
      conducted in 21 male mice (90 scans). Quantitative arterial recordings were
      feasible only in a minority of animals, showing an emphasized reaction to flicker
      light impulses (8 mice; 14 scans). A characteristic venous response to flicker
      light, however, could observed in the majority of animals. Repeated measurements
      resulted in a significant decrease of baseline venous diameter (7 mice; 7 scans,
      p < 0.05). Ex-vivo electroretinograms, performed after in-vivo DVA, demonstrated
      a significant reduction of transretinal signaling in animals with repeated DVA (n
      = 6, p < 0.001). CONCLUSIONS: To the best of our knowledge, this is the first non
      invasive study assessing murine retinal vessel response to flicker light with
      characteristic changes in NVC. The imaging system can be used for basic research
      and enables the investigation of retinal vessel dimension and function in control
      mice and genetically modified animals.

PMID- 30286111
TI  - Flexible foraging strategies in Pipistrellus pygmaeus in response to abundant but
      ephemeral prey.
AB  - There is growing recognition that with sympathetic management, plantation forests
      may contain more biodiversity than previously thought. However, the extent to
      which they may support bat populations is contentious. Many studies have
      demonstrated active avoidance of coniferous plantations and attributed this to
      the lack of available roost sites and low invertebrate density. In contrast,
      other work, carried out in plantation dominated landscapes have shown that
      certain bat species are able to exploit these areas. However, the extent to which
      bats use plantations for roosting and foraging, or simply move through the
      plantation matrix to access more favourable sites is unclear. We radio tracked
      female Pipistrellus pygmaeus over two summers to establish the extent to which
      individual bats use Sitka Spruce plantations in southern Scotland for foraging
      and roosting and assess the implications for felling operations on bats.
      Maternity roosts identified (n = 17) were in all in buildings and most were large
      (> 500 individuals). We found no evidence of bats roosting in mature Sitka Spruce
      crop trees, although several bats used roosts in old or dead beech and oak trees
      as an alternative to their main maternity roost. Home ranges were much larger
      (mean 9.6 +/- 3.12 km2) than those reported from other studies (0.6-1.6 km2), and
      it is likely that roost availability rather than food abundance constrains P.
      pygmaeus use of Sitka Spruce plantations. At the landscape scale, most
      individuals selected coniferous habitats over other habitat types, covering large
      distances to access plantation areas, whilst at a local scale bats used forest
      tracks to access water, felled stands or patches of broadleaf cover within the
      plantation. Sitka Spruce plantations support a high abundance of Culicoides
      impuctatus, the Highland midge which may act as a reliable and plentiful food
      source for females during lactation, an energetically expensive period. The use
      of felled stands for foraging by bats has implications for forest management as
      wind turbines, following small-scale felling operations, are increasingly being
      installed in plantations; wind turbines have been associated with high bat
      mortality in some countries. Decisions about siting wind turbines in upland
      plantations should consider the likelihood of increased bat activity post
      felling.

PMID- 30286112
TI  - Caricaturing faces to improve identity recognition in low vision simulations: How
      effective is current-generation automatic assignment of landmark points?
AB  - PURPOSE: Previous behavioural studies demonstrate that face caricaturing can
      provide an effective image enhancement method for improving poor face identity
      perception in low vision simulations (e.g., age-related macular degeneration,
      bionic eye). To translate caricaturing usefully to patients, assignment of the
      multiple face landmark points needed to produce the caricatures needs to be fully
      automatised. Recent development in computer science allows automatic face
      landmark detection of 68 points in real time and in multiple viewpoints. However,
      previous demonstrations of the behavioural effectiveness of caricaturing have
      used higher-precision caricatures with 147 landmark points per face, assigned by
      hand. Here, we test the effectiveness of the auto-assigned 68-point caricatures.
      We also compare this to the hand-assigned 147-point caricatures. METHOD: We
      assessed human perception of how different in identity pairs of faces appear,
      when veridical (uncaricatured), caricatured with 68-points, and caricatured with
      147-points. Across two experiments, we tested two types of low-vision images: a
      simulation of blur, as experienced in macular degeneration (testing two blur
      levels); and a simulation of the phosphenised images seen in prosthetic vision
      (at three resolutions). RESULTS: The 68-point caricatures produced significant
      improvements in identity discrimination relative to veridical. They were
      approximately 50% as effective as the 147-point caricatures. CONCLUSION:
      Realistic translation to patients (e.g., via real time caricaturing with the
      enhanced signal sent to smart glasses or visual prosthetic) is approaching
      feasibility. For maximum effectiveness software needs to be able to assign
      landmark points tracing out all details of feature and face shape, to produce
      high-precision caricatures.

PMID- 30286113
TI  - Perfidious synaptic transmission in the guinea-pig auditory brainstem.
AB  - The presence of 'giant' synapses in the auditory brainstem is thought to be a
      specialization designed to encode temporal information to support perception of
      pitch, frequency, and sound-source localisation. These 'giant' synapses have been
      found in the ventral cochlear nucleus, the medial nucleus of the trapezoid body
      and the ventral nucleus of the lateral lemniscus. An interpretation of these
      synapses as simple relays has, however, been challenged by the observation in the
      gerbil that the action potential frequently fails in the ventral cochlear
      nucleus. Given the prominence of these synapses it is important to establish
      whether this phenomenon is unique to the gerbil or can be observed in other
      species. Here we examine the responses of units, thought to be the output of
      neurons in receipt of 'giant' synaptic endings, in the ventral cochlear nucleus
      and the medial nucleus of the trapezoid body in the guinea pig. We found that
      failure of the action-potential component, recorded from cells in the ventral
      cochlear nucleus, occurred in ~60% of spike waveforms when recording spontaneous
      activity. In the medial nucleus of the trapezoid body, we did not find evidence
      for action-potential failure. In the ventral cochlear nucleus action-potential
      failures transform the receptive field between input and output of bushy cells.
      Additionally, the action-potential failures result in "non-primary-like" temporal
      adaptation patterns. This is important for computational models of the auditory
      system, which commonly assume the responses of ventral cochlear nucleus bushy
      cells are very similar to their "primary like" auditory-nerve-fibre inputs.

PMID- 30286114
TI  - A comparison of Kato-Katz technique to three other methods for diagnosis of
      Amphimerus spp. liver fluke infection and the prevalence of infection in Chachi
      Amerindians of Ecuador.
AB  - BACKGROUND: Recently, a high prevalence of infection by the liver fluke
      Amphimerus spp. has been documented in the Chachi Amerindians of Ecuador. For
      diagnosis, no studies exist that compare the sensitivity of different
      coproparasitological detection techniques. The present study compares the Kato
      Katz technique with three other coproparasitological methods for detecting eggs
      of Amphimerus in stools, as well as determines the prevalence of infection in
      Chachi residents in a Tropical rain forest area in the northwest coast of
      Ecuador. METHODOLOGY/RESULTS: A total of 105 samples, utilizing the Kato-Katz
      technique (KK), the spontaneous sedimentation technique in tube (SSTT), the
      formalin-ether concentration technique (FEC), and direct smear microscopy (DM),
      were examined. Combining the four methods (fixed "gold" standard), 38 samples
      were positive with a prevalence of infection of 36.2%. The sensitivities of
      individual methods were 71%, 58%, 50% and 3% for KK, SSTT, FEC, and DM
      respectively. Our results indicated that KK alone had the best performance,
      detecting 27 (71%) of the 38 positive samples. The combination of KK and SSTT
      detected amphimeriasis in 36 (95%) samples, and KK and FEC in 31 (82%) samples.
      CONCLUSIONS: DM showed the lowest sensitivity, which raises concern for its
      value, because it is the standard technique for stool examination for detection
      of parasites in both public and private laboratories in Ecuador. SSTT alone
      detected eggs in 22 samples (58%) and would be recommended for field studies
      because of its simplicity. Performing two techniques on a single sample enhances
      the detection of Amphimerus infection. Its sensitivity is relative to a fixed
      "gold" standard, determined as the combined results of the four techniques
      performed. This study confirms the high prevalence of human infection by
      Amphimerus in the indigenous Chachi group where the first human cases were
      described.

PMID- 30286116
TI  - Waterbird response to variable-timing of drawdown in rice fields after winter
      flooding.
AB  - Wetland loss and degradation have been extensive across the world, especially in
      California's Central Valley where over 90% of the natural wetlands have been
      converted to agricultural and urban uses. In the Central Valley today, a much
      smaller network of managed wetlands and flooded agricultural fields supports
      almost five million waterfowl and half a million shorebirds. Over 50% of
      waterbird habitat in the Central Valley is provided by flooded agricultural land,
      primarily rice (Oryza sativa). Each year non-breeding waterbird habitat decreases
      in the late winter as flooded agricultural fields are drained after waterfowl
      hunting season in late-January to prepare for the next crop. This study evaluated
      a practice called 'variable drawdown' that involves delaying the removal of water
      from rice fields by 1, 2, and 3 weeks to extend the availability of flooded
      habitat later into February and March. We studied waterbird response to variable
      drawdown in 2012 and 2013 at twenty rice farms throughout the northern half of
      the Central Valley. The staggered drawdown created a mosaic of water depths
      throughout the six-week study period. The 3-week delay in drawdown supported more
      dabbling ducks than earlier drawdowns in the first half of the study and more
      shorebirds and long-legged wading birds during the second half of the study. The
      timing of highest use of each drawdown treatment differed for each waterbird
      guild; dabbling ducks, geese and swans benefited at the beginning, then long
      legged wading birds, followed by shorebirds. Despite the presence of appropriate
      water depths for shorebirds across the treatments during the entire study period,
      shorebird densities were highest near the end of the study when the 3-week
      delayed drawdown was providing the majority of the habitat on the landscape. This
      suggests that shorebirds may have concentrated in our study fields due to
      decreasing availability of shallow water habitat elsewhere. The practice of
      variable drawdown successfully extended the availability of waterbird habitat
      provided by post-harvest flooded rice fields later into winter.

PMID- 30286115
TI  - An improved method for extraction of polar and charged metabolites from
      cyanobacteria.
AB  - A key requirement for 13C Metabolic flux analysis (13C-MFA), a widely used
      technique to estimate intracellular metabolic fluxes, is an efficient method for
      the extraction of intermediate metabolites for analysis via liquid chromatography
      mass spectrometry (LC/MS). The 13C isotopic labeling results in further
      distribution of an already sparse pool of intermediate metabolites into
      isotopologues, each appearing as a separate chromatographic feature. We examined
      some of the reported solvent systems for the extraction of polar intracellular
      metabolites from three strains of cyanobacteria of the genus Synechococcus, viz.,
      Synechococcus sp. PCC 7002, Synechococcus elongatus PCC 7942, and a newly
      isolated Synechococcus elongatus PCC 11801 (manuscript under review). High
      resolution-LC/MS was used to assess the relative abundance of the extracted
      metabolites. The different solvent systems used for extraction led to
      statistically significant changes in the extraction efficiency for a large number
      of metabolites. While a few hundred m/z features or potential metabolites were
      detected with different solvent systems, the abundance of over a quarter of all
      metabolites varied significantly from one solvent system to another. Further, the
      extraction methods were evaluated for a targeted set of metabolites that are
      important in 13C-MFA studies of photosynthetic organisms. While for the strain
      PCC 7002, the reported method using methanol-chloroform-water system gave
      satisfactory results, a mild base in the form of NH4OH had to be used in place of
      water to achieve adequate levels of extraction for PCC 7942 and PCC 11801. While
      minor changes in extraction solvent resulted in dramatic changes in the
      extraction efficiency of a number of compounds, certain metabolites such as amino
      acids and organic acids were adequately extracted in all the solvent systems
      tested. Overall, we present a new improved method for extraction using a methanol
      chloroform-NH4OH system. Our method improves the extraction of polar compounds
      such as sugar phosphates, bisphosphates, that are central to 13C-MFA studies.

PMID- 30286117
TI  - Antimicrobial activity of NO-releasing compounds against periodontal pathogens.
AB  - This study describes the successful synthesis of nitric oxide (NO)-releasing
      compounds with biodegradable and injectable properties and demonstrates that the
      kinetics of NO release vary according to the type of NO donor. The antimicrobial
      activity of NO-releasing compounds against three common periodontal pathogens,
      i.e., Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and
      Actinomyces israelii, was investigated using a susceptibility assay. Human
      gingival fibroblasts were treated with NO-releasing compounds at the minimum
      concentrations required for bacterial growth and cytotoxicity was evaluated using
      the MTT cell proliferation assay. Our results suggest that NO-releasing compounds
      can be used topically to treat both gram-negative and gram-positive periodontal
      pathogens. Comparison of the antimicrobial activity and cytotoxicity assay
      results between the NO-releasing compounds revealed that an NO donor comprising a
      macromolecule without surface charge, a lower instantaneous NO concentration, and
      an adequate supply of NO were associated with a strong bactericidal effect and
      low cytotoxicity. NO-releasing compounds with these properties may be suitable
      for treatment of periodontitis.

PMID- 30286118
TI  - The medical assistance system and inpatient health care provision: Empirical
      evidence from short-term hospitalizations in Japan.
AB  - This paper uses two nationally representative sets of medical claims data from
      medical assistance and universal public health insurance systems to examine how
      medical assistance system assignment affects short-term inpatient health care
      provision. In Japan, the medical assistance system, which is part of a public
      assistance system, provides medical care services for its beneficiaries without
      imposing any financial burdens, such as copayments or advance premium payments.
      These circumstances can lead to inpatient costs, as physicians may provide more
      treatments because there is a financial incentive. Because the assignment of
      public assistance in Japan is not random but is subject to means testing by the
      local government, I employ the instrumental variable model to control the
      potential correlation. I find that medical expenditure is significantly higher
      for medical assistance patients than for universal public health insurance
      patients, with an arc elasticity of approximately 0.20. This elasticity is
      slightly greater than that found for inpatient care in the randomized RAND Health
      Insurance Experiment and recent empirical studies on low-income populations. In
      addition, the elasticities for patients who receive medication, treatment and
      surgery are greater.

PMID- 30286119
TI  - Agreement between CDC/NHSN surveillance definitions and ECDC criteria in
      diagnosis of healthcare-associated infections in Serbian trauma patients.
AB  - After three national point prevalence studies (PPS) of healthcare associated
      infections (HAI) conducted in Serbian acute care hospitals using US (CDC/NHSN)
      surveillance definitions, Serbia is about to switch to European (ECDC) criteria
      for the purpose of the fourth HAI PPS. The aim of this study was to compare the
      US and the European HAI definitions in Serbian trauma intensive care unit (ICU).
      Prospective surveillance was performed at two surgical-trauma ICUs of the
      Emergency department of Clinical Center of Serbia. HAIs were prospectively
      diagnosed by experienced clinician and epidemiologists using both types of HAI
      definitions simultaneously. The level of agreement between two case definitions
      was assessed by Cohen's kappa statistic (k). Of 406 patients, 107 (26.3%)
      acquired at least one HAI (total of 107 according to US definitions and 141
      according to European criteria). For microbiologically confirmed pneumonia
      agreement was k = 0.99 (95% CI, 0.96-1.00) and for clinically defined k = 0.86
      (95% CI, 0.58-1.00). Agreement for bloodstream infections (BSI) was 0.79 (CI 95%,
      0.70-0.89). When secondary BSI was excluded from the European classification,
      (30.9% of all BSI), concordance was k = 1.00 and when microbiologically confirmed
      catheter related BSI were reported separately as recommended by latest ECDC
      protocol update, (20.0% of all BSI), concordance was 0.60 (CI 95%, 0.41-0.80). No
      agreement was found between CLABSI and CRI while slight agreement was found when
      compared CLABSI and CRI3 (k = 0.11; 95%CI, 0.0-0.22). Agreement for overall UTI
      was moderate (k = 0.66; 95%CI, 0.53-0.79) while for microbiologically-confirmed
      symptomatic UTI was perfect (k = 1.00). For CAUTI good agreement was observed (k
      = 0.77; 95%CI, 0.34-1.0). Microbiological confirmation of PN and UTI should be
      stimulated and comparison of BSI should be done with emphasis on whether
      secondary BSI is included.

PMID- 30286120
TI  - The beneficial application of preoperative 3D printing for surgical stabilization
      of rib fractures.
AB  - OBJECTIVES: The beneficial application of three-dimensional (3D) printing for
      surgical stabilization of rib fractures (SSRF) has never been proposed in the
      literature before. The aim of this study was to verify patients' surgical
      outcomes when utilizing preoperative three-dimensional printing for SSRF.
      METHODS: We retrospectively reviewed the records of all consecutive patients who
      were treated at our hospital for SSRF from July 2015 to December 2017. The
      patients were divided into two groups according to whether or not 3D printing was
      utilized. RESULTS: Forty-eight patients who underwent SSRF at our hospital were
      enrolled. Of them, three patients underwent bilateral surgeries. The patients
      with application of preoperative 3D printing for SSRF had statistically
      significant associations with shorter operation time per fixed plate (p < 0.001),
      and a smaller incision length (p < 0.001). CONCLUSIONS: We present an useful
      technique involving 3D printing for promoting SSRF significantly with shorter
      operation time and an appropriate incision length.

PMID- 30286121
TI  - Large-scale mitochondrial DNA analysis reveals new light on the phylogeography of
      Central and Eastern-European Brown hare (Lepus europaeus Pallas, 1778).
AB  - European brown hare, Lepus europaeus, from Central and Eastern European countries
      (Hungary, Poland, Serbia, Lithuania, Romania, Georgia and Italy) were sampled,
      and phylogenetic analyses were carried out on two datasets: 1.) 137 sequences
      (358 bp) of control region mtDNA; and 2.) 105 sequences of a concatenated
      fragment (916 bp), including the cytochrome b, tRNA-Thr, tRNA-Pro and control
      region mitochondrial DNA. Our sequences were aligned with additional brown hare
      sequences from GenBank. A total of 52 and 51 haplotypes were detected within the
      two datasets, respectively, and assigned to two previously described major
      lineages: Anatolian/Middle Eastern (AME) and European (EUR). Furthermore, the
      European lineage was divided into two subclades including South Eastern European
      (SEE) and Central European (CE). Sympatric distribution of the lineages of the
      brown hare in South-Eastern and Eastern Europe revealed contact zones there. BAPS
      analysis assigned sequences from L. europaeus to five genetic clusters, whereas
      CE individuals were assigned to only one cluster, and AME and SEE sequences were
      each assigned to two clusters. Our findings uncover numerous novel haplotypes of
      Anatolian/Middle Eastern brown hare outside their main range, as evidence for the
      combined influence of Late Pleistocene climatic fluctuations and anthropogenic
      activities in shaping the phylogeographic structure of the species. Our results
      support the hypothesis of a postglacial brown hare expansion from Anatolia and
      the Balkan Peninsula to Central and Eastern Europe, and suggest some slight
      introgression of individual haplotypes from L. timidus to L. europaeus.

PMID- 30286122
TI  - Is obstructive sleep apnea associated with difficult airway? Evidence from a
      systematic review and meta-analysis of prospective and retrospective cohort
      studies.
AB  - BACKGROUND: Difficult airway management and obstructive sleep apnea may
      contribute to increased risk of perioperative morbidity and mortality. The
      objective of this systematic review and meta-analysis (SRMA) is to evaluate the
      evidence of a difficult airway being associated with obstructive sleep apnea
      (OSA) patients undergoing surgery. METHODS: The standard databases were searched
      from 1946 to April 2017 to identify the eligible articles. The studies which
      included adult surgical patients with either suspected or diagnosed obstructive
      sleep apnea must report at least one difficult airway event [either difficult
      intubation (DI), difficult mask ventilation (DMV), failed supraglottic airway
      insertion or difficult surgical airway] in sleep apnea and non-sleep apnea
      patients were included. RESULTS: Overall, DI was 3.46-fold higher in the sleep
      apnea vs non-sleep apnea patients (OSA vs. non-OSA: 13.5% vs 2.5%; OR 3.46; 95%
      CI: 2.32-5.16, p <0.00001). DMV was 3.39-fold higher in the sleep apnea vs non
      sleep apnea patients (OSA vs. non-OSA: 4.4% vs 1.1%; OR 3.39; 95% CI: 2.74-4.18,
      p <0.00001). Combined DI and DMV was 4.12-fold higher in the OSA vs. non-OSA
      patients (OSA vs. non-OSA: 1.1% vs 0.3%; OR 4.12; 95% CI: 2.93-5.79, p <0.00001).
      There was no significant difference in the supraglottic airway failure rates in
      the sleep apnea vs non-sleep apnea patients (OR: 1.34; 95% CI: 0.70-2.59; p =
      0.38). Meta-regression to adjust for various subgroups and baseline confounding
      factors did not impact the final inference of our results. CONCLUSION: This SRMA
      found that patients with obstructive sleep apnea had a three to four-fold higher
      risk of difficult intubation or mask ventilation or both, when compared to non
      sleep apnea patients.

PMID- 30286123
TI  - An improved memory-based collaborative filtering method based on the TOPSIS
      technique.
AB  - This paper describes an approach for improving the accuracy of memory-based
      collaborative filtering, based on the technique for order of preference by
      similarity to ideal solution (TOPSIS) method. Recommender systems are used to
      filter the huge amount of data available online based on user-defined
      preferences. Collaborative filtering (CF) is a commonly used recommendation
      approach that generates recommendations based on correlations among user
      preferences. Although several enhancements have increased the accuracy of memory
      based CF through the development of improved similarity measures for finding
      successful neighbors, there has been less investigation into prediction score
      methods, in which rating/preference scores are assigned to items that have not
      yet been selected by a user. A TOPSIS solution for evaluating multiple
      alternatives based on more than one criterion is proposed as an alternative to
      prediction score methods for evaluating and ranking items based on the results
      from similar users. The recommendation accuracy of the proposed TOPSIS technique
      is evaluated by applying it to various common CF baseline methods, which are then
      used to analyze the MovieLens 100K and 1M benchmark datasets. The results show
      that CF based on the TOPSIS method is more accurate than baseline CF methods
      across a number of common evaluation metrics.

PMID- 30286124
TI  - The effect of naltrexone as a carboplatin chemotherapy-associated drug on the
      immune response, quality of life and survival of dogs with mammary carcinoma.
AB  - The objective of this study was to evaluate the effect of low-dose naltrexone
      (LDN) as a carboplatin chemotherapy-associated drug in female dogs with mammary
      carcinoma in benign mixed tumors (MC-BMT) after mastectomy and to assess its
      association with quality of life and survival rates. Sixty female dogs were
      included in this study, all of which had histopathological diagnosis of MC-BMT
      and were divided into three groups: G1 (control), consisting of animals submitted
      only to mastectomy with or without regional metastasis; G2, composed of treated
      animals that did not present with metastasis; and G3, treated dogs that presented
      with metastasis. G2 and G3 were also subdivided according to the treatment
      administered: chemotherapy alone (MC-BMT(-) C/MC-BMT(+) C) or LDN and
      chemotherapy (MC-BMT(-) C+LDN/MC-BMT(+) C+LDN). All animals were subjected to
      clinical evaluation, mastectomy, peripheral blood lymphocyte immunophenotyping,
      beta-endorphin and met-enkephalin quantification, and evaluation of survival
      rates and quality of life scores. The results showed higher serum concentrations
      of beta-endorphin and met-enkephalin, fewer chemotherapy-related side effects,
      and better quality of life and survival rates in the LDN-treated groups than in
      LDN-untreated groups (P < 0.05). Evaluation of clinical and pathological
      parameters indicated a significant association between the use of LDN and both
      prolonged survival and enhanced quality of life. These results indicate that LDN
      is a viable chemotherapy-associated treatment in female dogs with MC-BMT,
      maintaining their quality of life and prolonging survival rates.

PMID- 30286125
TI  - Examining the impact of distance as a contextual cue in evaluative conditioning.
AB  - According to a symbolic perspective on EC, pairings constitute a relational
      contextual cue in the environment. It is the relationship between stimuli as cued
      by the pairing (i.e., pairings = similar) that determines the observed change in
      liking. Across five pre-registered studies (N = 747) we manipulated the absolute
      or relative distance between different pairs of conditioned (CS) and
      unconditioned stimuli (US) under the assumption that this would influence the
      type of relation that the pairings would cue (i.e., close = similar; far =
      different). In all five studies we obtained repeated and strong evidence that
      stimulus pairings led to changes in implicit and explicit evaluations. Although
      we found that these effects were moderated by absolute distance manipulations,
      evidence did not emerge indicating that those same effects were moderated by
      relative distance manipulations. These findings fail to provide strong support
      for a symbolic perspective on EC. We discuss the implications of our findings as
      well as future research in this area.

PMID- 30286126
TI  - Cytoplasmic, nuclear, and total PBK/TOPK expression is associated with prognosis
      in colorectal cancer patients: A retrospective analysis based on
      immunohistochemistry stain of tissue microarrays.
AB  - OBJECTIVE: PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK)
      regulates components of the cell cycle, including cell growth, immune responses,
      DNA damage repair, apoptosis, and inflammation. PBK/TOPK may also accelerate
      tumorigenesis in colorectal cancer. METHODS: We investigated the impact of
      PBK/TOPK on the clinical outcome of colorectal cancer patients to further
      identify its role in colorectal cancer. PBK/TOPK immunoreactivity was analyzed by
      immunohistochemistry in 162 cancer specimens from primary colorectal cancer
      patients. RESULTS: The mean follow-up time after surgery was 5.4 years (medium:
      3.9 years; range 0.01 to 13.1 years). The prognostic value of PBK/TOPK on overall
      survival was determined by Kaplan-Meier analysis and Cox proportional hazard
      models. PBK/TOPK was expressed in both the cytoplasm and nucleus. High PBK/TOPK
      expression in tumor cells was significantly associated with advanced T value. The
      5-year survival rate was greater for patients with high total PBK/TOPK expression
      than with low PBK/TOPK expression (58.3% vs 34.4%, P = 0.005). Multivariate
      analyses showed that low-scoring cytoplasmic PBK/TOPK, negative nuclear PBK/TOPK,
      low total PBK/TOPK, and advanced tumor stage were correlated with poor overall
      patient survival. CONCLUSIONS: We suggest that PBK/TOPK expression, detected by
      IHC staining, could be used as an independent prognostic marker for colorectal
      cancer patients.

PMID- 30286127
TI  - Implementation of the hybrid course on basic wheelchair service provision for
      Colombian wheelchair service providers.
AB  - INTRODUCTION: People with mobility impairments often rely on wheelchairs as their
      primary means of mobility. Untrained wheelchair service providers may provide
      inappropriate wheelchairs and services which result in negative consequences in
      wheelchair users' health, quality of life, safety, and social participation. This
      study aimed to evaluate the influence of the Spanish Hybrid Course on Basic
      Wheelchair Service Provision, a training based on the World Health Organization's
      Wheelchair Service Training Program-Basic Level, to increase knowledge in basic
      level wheelchair service provision among a group of wheelchair service providers
      from Colombia. In addition, we developed a satisfaction survey which participants
      completed after the training to understand levels of satisfaction with the
      training intervention. METHODS: A quasi-experimental study was conducted to
      evaluate changes in basic level wheelchair knowledge using the Wheelchair Service
      Provision-Basic Test. Paired sample t tests were used to assess pre-and post
      training changes in basic level wheelchair knowledge. The Hybrid Satisfaction
      Survey was developed in collaboration with a multidisciplinary, international
      stakeholders' group. The survey's construct of interest was level of satisfaction
      determined by interaction, instructor, instruction methodology, content, and
      technology, using a five-point Likert scale (0 = strongly disagree to 4 =
      strongly agree). The survey was completed anonymously after the training
      intervention and analyzed using frequencies and percentages. RESULTS: Fifteen
      wheelchair service providers in Colombia completed the Spanish Hybrid Course.
      Mean post-scores were significantly higher (Mean (M) = 56.13, Standard Deviation
      (SD) = 7.8), than pre-assessment scores (M = 50.07, SD = 8.38, t(14) = 4.923, p =
      <0.0001). Participants who completed the surveys (N = 15) reported that the
      Spanish Hybrid Course was well received, with 98.66% of responses distributed in
      favorable levels (>3). CONCLUSIONS: The Spanish Hybrid Course proved to be
      effective in increasing basic level wheelchair knowledge with a high satisfaction
      level among participants. Further testing is needed to evaluate the effectiveness
      of this course across different individuals and countries as a potential tool to
      build professional capacity in basic level wheelchair provision.

PMID- 30286128
TI  - Determining fuel moisture thresholds to assess wildfire hazard: A contribution to
      an operational early warning system.
AB  - Fuel moisture content (FMC) is an important fuel property for assessing wildfire
      hazard, since it influences fuel flammability and fire behavior. The relationship
      between FMC and fire activity differs among land covers and seems to be a
      property of each ecosystem. Our objectives were to analyze pre-fire FMC among
      different land covers and to propose a wildfire hazard classification for the
      Sierras Chicas in the Chaco Serrano subregion (Argentina), by analyzing pre-fire
      FMC distributions observed for grasslands, shrublands and forests and using
      percentiles to establish thresholds. For this purpose, we used a fire database
      derived from Landsat imagery (30 m) and derived FMC maps every 8 days from 2002
      to 2016 using MODIS reflectance products and empirical equations of FMC. Our
      results indicated that higher FMC constrains the extent of wildfires, whereas at
      lower FMC there are other factors affecting their size. Extreme and high fire
      hazard thresholds for grasslands were established at FMC of 55% and 67%
      respectively, at 72% and 105% for forests and at 106% and 121% for shrublands.
      Our FMC thresholds were sensitive to detect extreme fire hazard conditions during
      years with high fire activity in comparison to average conditions. The
      differences in the distributions of pre-fire FMC among land covers and between
      ecosystems highlighted the need to locally determine land cover-specific FMC
      thresholds to assess wildfire hazard. Our wildfire hazard classification applied
      to FMC maps in an operational framework will contribute to improving early
      warning systems in the Sierras Chicas. However, moisture alone is not sufficient
      to represent true fire hazard in Chaco forests and the combination with other
      variables would provide better hazard assessments. These operational wildfire
      hazard maps will help to better allocation of fire protective resources to
      minimize negative impact on people, property and ecosystems. To the best of our
      knowledge, this is the first study analyzing pre-fire FMC over several fire
      seasons in a non-Mediterranean ecosystem, aiming at assessing wildfire hazard.

PMID- 30286129
TI  - Retention of knowledge and skills after Emergency Obstetric Care training: A
      multi-country longitudinal study.
AB  - OBJECTIVE: To determine retention of knowledge and skills after standardised
      "skills and drills" training in Emergency Obstetric Care. DESIGN: Longitudinal
      cohort study. SETTING: Ghana, Malawi, Nigeria, Kenya, Tanzania and Sierra Leone.
      POPULATION: 609 maternity care providers, of whom 455 were nurse/midwives (NMWs).
      METHODS: Knowledge and skills assessed before and after training, and, at 3, 6, 9
      and 12 months. Analysis of variance to explore differences in scores by country
      and level of healthcare facility for each cadre. Mixed effects regression
      analysis to account for potential explanatory factors including; facility type,
      years of experience providing maternity care, months since training and number of
      repeat assessments. MAIN OUTCOME MEASURES: Change in knowledge and skills.
      RESULTS: Before training the overall mean (SD) score for skills was 48.8% (11.6%)
      and 65.6% (10.7%). for knowledge. After training the mean (95% CI) relative
      improvement in knowledge was 30.8% (29.1% - 32.6%) and 59.8% (58.6%- 60.9%) for
      skills. Mean scores for knowledge and skills at each subsequent assessment
      remained between those immediately post-training and those at 3 months. NMWs who
      attended all four assessments demonstrated statistically better retention of
      skills (14.9%, 95% CI 7.8%, 22.0% p<0.001) but not knowledge (8.6%, 95% CI -0.3%,
      17.4%. p = 0.06) compared to those who attended one or two assessments only.
      Health care facility level or experience were not determinants of retention.
      CONCLUSIONS: After training, healthcare providers retain knowledge and skills for
      up to 12 months. This effect can likely be enhanced by short repeat skills
      training sessions, or, 'fire drills'.

PMID- 30286130
TI  - An easy and safe training method for trunk function improves mobility in total
      knee arthroplasty patients: A quasi-randomized controlled trial.
AB  - OBJECTIVE: Total knee arthroplasty (TKA) is aimed mainly at reducing pain and
      restoring mobility. However, mobility deficits can persist even longer than 1
      year. The trunk function and movement velocity of any region have been recently
      recognized to be critical for determining mobility in older people. Therefore,
      the main goal of this quasi-randomized trial is to clarify the effectiveness of a
      novel training method, the seated side tapping (SST) training, for improving
      mobility by focusing on movement velocity of trunk function in the short term
      after TKA. METHODS: SST training consists of side trunk movements repeated as
      quickly as possible in a seated position. All participants after TKA were
      randomly assigned to the SST training group (n = 37) or control training group (n
      = 38). The participants in the SST group performed SST training plus the standard
      rehabilitation program 5 days per week for 3 weeks after TKA, while the control
      group performed only the standard rehabilitation programs. The primary outcome
      was the effect of SST training on mobility, indicated by gait speed and the timed
      up and go test (TUG) time. Measurements were performed before and 1, 2, and 3
      weeks after surgery. RESULTS: At all-time points, the patients in the SST group
      showed significantly better mobility, despite that knee function, represented by
      muscle strength, range of motion, and degree of pain at the knee joint, was
      similar in both groups. The difference in gait speed between the groups was >0.1
      m/s at all time points, which is clinically significant. CONCLUSION: SST training
      significantly improved patients' mobility within 3 weeks after TKA, despite that
      no additional benefit was observed in knee function. The findings in this study
      indicate that SST training may be considered as a part of the rehabilitation
      program after TKA, although further evaluation of its long-term effectiveness is
      needed. TRIAL REGISTRATION: University Hospital Medical Information Network
      Clinical Trials Registry (UMIN-CTR; UMIN000027909).

PMID- 30286131
TI  - Health-related quality of life in patients with autoimmune hepatitis: A
      questionnaire survey.
AB  - AIM: Health-related quality of life is impaired in patients with autoimmune
      hepatitis, but the association between health-related quality of life and
      patients' backgrounds remains unknown. We assessed health-related quality of life
      in patients with autoimmune hepatitis and identified factors associated with its
      impairment. METHODS: We assessed health-related quality of life in patients with
      autoimmune hepatitis, patients with chronic hepatitis C, and healthy subjects
      using the Japanese version of the Chronic Liver Disease Questionnaire and the 36
      Item Short Form Survey. We compared health-related quality of life in patients
      with autoimmune hepatitis with that of patients with chronic hepatitis C and
      healthy subjects. RESULTS: A total of 265 patients with autoimmune hepatitis, 88
      patients with chronic hepatitis C, and 97 healthy subjects were enrolled; most
      patients were women. The median ages of patients were 65, 66, and 57 years,
      respectively. Of these patients with autoimmune hepatitis, 10.6% and 57.0% had
      cirrhosis and comorbid diseases, respectively. The overall Chronic Liver Disease
      Questionnaire scores (5.5 vs. 6.2, P < 0.001) and physical (48.1 vs. 54.2, P <
      0.001) and mental (51.8 vs. 55.0, P = 0.004) component summaries of 36-Item Short
      Form Survey were significantly lower in patients with autoimmune hepatitis than
      in healthy subjects, and similar to scores in patients with chronic hepatitis C.
      Having cirrhosis, comorbid diseases, and treatment for autoimmune hepatitis were
      associated with impaired health-related quality of life among patients with
      autoimmune hepatitis. In particular, prednisolone use was associated with lower
      scores on the worry domain of the Chronic Liver Disease Questionnaire.
      CONCLUSIONS: Patients with autoimmune hepatitis showed impairment in health
      related quality of life, which was associated with not only disease progression,
      but also comorbid diseases and treatment. Ways to improve health-related quality
      of life should be considered in patients with AIH when disease outcome is not
      favorable and when using prednisolone.

PMID- 30286132
TI  - CRISPR deletion of MIEN1 in breast cancer cells.
AB  - Migration and Invasion Enhancer (MIEN1) is an oncogene which is involved in
      facilitating motility of cancer cells through actin dynamics and gene expression.
      Increased MIEN1 expression in many types of tumors leads to disease progression
      and metastatic propensity. It is unclear precisely how MIEN1 is involved in this
      process and more studies are required to tease out the mechanisms. Here we show
      that Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) genome
      editing effectively produced specific genomic deletions in the MIEN1 gene which
      led to the abrogation of its expression in breast cancer cells. The single guide
      RNAs (sgRNAs) mediated targeting of MIEN1 was specific and none of the clones
      screened for off-target cleavage revealed any insertions or deletions (indels).
      Additionally, disruption of the MIEN1 gene did not alter the cell morphology,
      growth, proliferation or survival. Knocking out MIEN1 in these breast cancer
      cells will allow future studies to determine the exact role MIEN1 plays in breast
      tumor metastasis, which might lead to production of novel therapeutics to treat
      this and other cancers.

PMID- 30286134
TI  - Understanding intersections of social determinants of maternal healthcare
      utilization in Uttar Pradesh, India.
AB  - OBJECTIVE: To explore intersections of social determinants of maternal healthcare
      utilization using the Classification and Regression Trees (CART) algorithm which
      is a machine-learning method used to construct prediction models. METHODS:
      Institutional review board approval for this study was granted from Public Health
      Service-Ethical Review Board (PHS-ERB) and from the Health Ministry Screening
      Committee (HMSC) facilitated by Indian Council for Medical Research (ICMR). IRB
      review and approval for the current analyses was obtained from University of
      California, San Diego. Cross-sectional data were collected from women with
      children aged 0-11 months (n = 5,565) from rural households in 25 districts of
      Uttar Pradesh, India. Participants were surveyed on maternal healthcare
      utilization including registration of pregnancy (model-1), receipt of antenatal
      care (ANC) during pregnancy (model-2), and delivery at health facilities (model 
      3). Social determinants of health including wealth, social group, literacy,
      religion, and early age at marriage were captured during the survey. The
      Classification and Regression Tree (CART) algorithm was used to explore
      intersections of social determinants of healthcare utilization. RESULTS: CART
      analyses highlight the intersections, particularly of wealth and literacy, in
      maternal healthcare utilization in Uttar Pradesh. Model-1 documents that women
      who are poorer, illiterate and Muslim are less likely to have their pregnancies
      registered (71.4% vs. 86.0% in the overall sample). Model-2 documents that
      poorer, illiterate women had the lowest ANC coverage (37.7% vs 45% in the overall
      sample). Model-3, developed for deliveries at health facilities, highlighted that
      illiterate and poor women have the lowest representation among facility
      deliveries (59.6% vs. 69% in the overall sample). CONCLUSION: This paper explores
      the interactions between determinants of maternal healthcare utilization
      indicators. The findings in this paper highlights that the interaction of wealth
      and literacy can play a very strong role in accentuating or diminishing
      healthcare utilization among women. The study also reveals that religion and
      women's age at marriage also interact with wealth and literacy to create
      substantial disparities in utilization. The study provides insights into the
      effect of intersections of determinants, and highlights the importance of using a
      more nuanced understanding of the impact of co-occurring forms of marginalization
      to effectively tackle inequities in healthcare utilization.

PMID- 30286135
TI  - High tension in sarcomeres hinders myocardial relaxation: A computational study.
AB  - Experiments have shown that the relaxation phase of cardiac sarcomeres during an
      isometric twitch is prolonged in muscles that reached a higher peak tension.
      However, the mechanism is not completely understood. We hypothesize that the
      binding of calcium to troponin is enhanced by the tension in the thin filament,
      thus contributing to the prolongation of contraction upon higher peak tension
      generation. To test this hypothesis, we developed a computational model of
      sarcomere mechanics that incorporates tension-dependence of calcium binding. The
      model was used to simulate isometric twitch experiments with time dependency in
      the form of a two-state cross-bridge cycle model and a transient intracellular
      calcium concentration. In the simulations, peak isometric twitch tension appeared
      to increase linearly by 51.1 KPa with sarcomere length from 1.9 MUm to 2.2 MUm.
      Experiments showed an increase of 47.3 KPa over the same range of sarcomere
      lengths. The duration of the twitch also increased with both sarcomere length and
      peak intracellular calcium concentration, likely to be induced by the inherently
      coupled increase of the peak tension in the thin filament. In the model
      simulations, the time to 50% relaxation (tR50) increased over the range of
      sarcomere lengths from 1.9 MUm to 2.2 MUm by 0.11s, comparable to the increased
      duration of 0.12s shown in experiments. Model simulated tR50 increased by 0.12s
      over the range of peak intracellular calcium concentrations from 0.87 MUM to 1.45
      MUM. Our simulation results suggest that the prolongation of contraction at
      higher tension is a result of the tighter binding of Ca2+ to troponin in areas
      under higher tension, thus delaying the deactivation of the troponin.

PMID- 30286136
TI  - Uncovering the relation between clinical reasoning and diagnostic accuracy - An
      analysis of learner's clinical reasoning processes in virtual patients.
AB  - BACKGROUND: Clinical reasoning is an important topic in healthcare training,
      assessment, and research. Virtual patients (VPs) are a safe environment to teach,
      assess and perform research on clinical reasoning and diagnostic accuracy. Our
      aim was to explore the details of the clinical reasoning process and diagnostic
      accuracy of undergraduate medical students when working with VPs using a concept
      mapping tool. METHODS: Over seven months we provided access to 67 German and 30
      English VPs combined with a concept mapping tool to visualize and measure the
      clinical reasoning process of identifying problems, differential diagnoses,
      recommended tests and treatment options, and composing a summary statement about
      a VP. A final diagnosis had to be submitted by the learners in order to conclude
      the VP scenario. Learners were allowed multiple attempts or could request the
      correct diagnosis from the system. RESULTS: We analyzed 1,393 completed concept
      maps from 317 learners. We found significant differences between maps with a
      correct final diagnosis on one or multiple attempts and maps in which learners
      gave up and requested the solution from the system. These maps had lower scores,
      fewer summary statements, and fewer problems, differential diagnoses, tests, and
      treatments. CONCLUSIONS: The different use patterns and scores between learners
      who had the correct final diagnosis on one or multiple attempts and those who
      gave up, indicate that diagnostic accuracy in the form of a correct final
      diagnosis on the first attempt has to be reconsidered as a sole indicator for
      clinical reasoning competency. For the training, assessment, and research of
      clinical reasoning we suggest focusing more on the details of the process to
      reach a correct diagnosis, rather than whether it was made in the first attempt.

PMID- 30286137
TI  - Novel gateway binary vectors for rapid tripartite DNA assembly and promoter
      analysis with various reporters and tags in the liverwort Marchantia polymorpha.
AB  - The liverwort Marchantia polymorpha is an emerging model species for basal
      lineage plant research. In this study, two Gateway cloning-compatible binary
      vector series, R4pMpGWB and R4L1pMpGWB, were generated to facilitate production
      of transgenic M. polymorpha. The R4pMpGWB series allows tripartite recombination
      of any promoter and any coding sequence with a specific reporter or tag.
      Reporters/tags for the R4pMpGWB series are GUS, ELuc(PEST), FLAG, 3*HA, 4*Myc,
      mRFP1, Citrine, mCitrine, ER-targeted mCitrine and nucleus-targeted mCitrine. The
      R4L1pMpGWB series is suitable for promoter analysis. R4L1pMpGWB vector structure
      is the same as that of R4pMpGWB vectors, except that the attR2 site is replaced
      with attL1, enabling bipartite recombination of any promoter with a reporter or
      tag. Reporters/tags for the R4L1pMpGWB series are GUS, G3GFP-GUS, LUC,
      ELuc(PEST), Citrine, mCitrine, ER-targeted mCitrine and mCitrine-NLS. Both vector
      series were functional in M. polymorpha cells. These vectors will facilitate the
      design and assembly of plasmid constructs and generation of transgenic M.
      polymorpha.

PMID- 30286133
TI  - Role of extracellular matrix and microenvironment in regulation of tumor growth
      and LAR-mediated invasion in glioblastoma.
AB  - The cellular dispersion and therapeutic control of glioblastoma, the most
      aggressive type of primary brain cancer, depends critically on the migration
      patterns after surgery and intracellular responses of the individual cancer cells
      in response to external biochemical cues in the microenvironment. Recent studies
      have shown that miR-451 regulates downstream molecules including AMPK/CAB39/MARK
      and mTOR to determine the balance between rapid proliferation and invasion in
      response to metabolic stress in the harsh tumor microenvironment. Surgical
      removal of the main tumor is inevitably followed by recurrence of the tumor due
      to inaccessibility of dispersed tumor cells in normal brain tissue. In order to
      address this complex process of cell proliferation and invasion and its response
      to conventional treatment, we propose a mathematical model that analyzes the
      intracellular dynamics of the miR-451-AMPK- mTOR-cell cycle signaling pathway
      within a cell. The model identifies a key mechanism underlying the molecular
      switches between proliferative phase and migratory phase in response to metabolic
      stress in response to fluctuating glucose levels. We show how up- or down
      regulation of components in these pathways affects the key cellular decision to
      infiltrate or proliferate in a complex microenvironment in the absence and
      presence of time delays and stochastic noise. Glycosylated chondroitin sulfate
      proteoglycans (CSPGs), a major component of the extracellular matrix (ECM) in the
      brain, contribute to the physical structure of the local brain microenvironment
      but also induce or inhibit glioma invasion by regulating the dynamics of the CSPG
      receptor LAR as well as the spatiotemporal activation status of resident
      astrocytes and tumor-associated microglia. Using a multi-scale mathematical
      model, we investigate a CSPG-induced switch between invasive and non-invasive
      tumors through the coordination of ECM-cell adhesion and dynamic changes in
      stromal cells. We show that the CSPG-rich microenvironment is associated with non
      invasive tumor lesions through LAR-CSGAG binding while the absence of
      glycosylated CSPGs induce the critical glioma invasion. We illustrate how high
      molecular weight CSPGs can regulate the exodus of local reactive astrocytes from
      the main tumor lesion, leading to encapsulation of non-invasive tumor and
      inhibition of tumor invasion. These different CSPG conditions also change the
      spatial profiles of ramified and activated microglia. The complex distribution of
      CSPGs in the tumor microenvironment can determine the nonlinear invasion
      behaviors of glioma cells, which suggests the need for careful therapeutic
      strategies.

PMID- 30286138
TI  - Effects of metformin use on total mortality in patients with type 2 diabetes and
      chronic obstructive pulmonary disease: A matched-subject design.
AB  - BACKGROUNDS: Few studies have investigated the therapeutic effects of metformin
      in patients with type 2 diabetes mellitus (T2DM) and chronic obstructive
      pulmonary disease (COPD). We compared the risk of all-cause mortality between
      metformin users and nonusers. METHODS: We conducted a retrospective cohort study
      for patients with T2DM and COPD who were enrolled between January 1, 2000 and
      June 30, 2012. Individuals with exacerbated symptoms who were hospitalized or
      sent to the emergency department (ED) were identified as having exacerbated COPD;
      outpatient claims were identified as having stable COPD. A total of 40,597
      metformin users and 39,529 nonusers comprised the cohort of stable COPD; 14,001
      metformin users and 21,613 nonusers comprised the cohort of exacerbated COPD.
      Users and nonusers were matched using propensity score (1:1). Our primary outcome
      was all-cause mortality. RESULTS: A total of 19,505 metformin users were matched
      to 19,505 nonusers in the cohort of diabetes with stable COPD. The mean follow-up
      time was 3.91 years. All-cause mortality was reported in 1326 and 1609 metformin
      users and nonusers, respectively. After multivariate adjustment, metformin users
      had lower risk of mortality (adjusted hazard ratio [aHR] = 0.84, p < 0.0001).
      Metformin users had significantly lower risk of noncardiovascular death (aHR =
      0.86, p = 0.0008). A total of 7721 metformin users were matched to 7721 nonusers
      in the cohort of diabetes with exacerbated COPD. The mean follow-up time was 3.18
      years. All-cause mortality was reported in 1567 and 1865 metformin users and
      nonusers, respectively. After multivariate adjustment, metformin users had
      significantly lower risk of mortality (aHR = 0.89, p = 0.002) and cardiovascular
      death (aHR = 0.70, p = 0.01). CONCLUSION: This large-series, nationwide cohort
      study demonstrated that metformin use could significantly lower the risk of all
      cause mortality in patients with T2DM and either stable or exacerbated COPD.

PMID- 30286139
TI  - A multispectral imaging approach integrated into the study of Late Antique
      textiles from Egypt.
AB  - This work explores the use of multispectral imaging (MSI) techniques applied to
      the investigation of Late Antique (c. 250-800 AD) textiles found in Egypt.
      Although the use of these techniques is well-established in the study of
      polychrome surfaces, they have only been sparingly and often unsystematically
      applied to the investigation of textiles. The aim of this work is therefore to
      bridge this gap by showing how this non-invasive, relatively inexpensive and
      portable methodology can be used to map the photoluminescence and reflective
      characteristics of textiles under different wavelengths of light, and to provide
      qualitative and holistic insights into the chemical nature of the materials that
      compose them. Standardised acquisition and post-processing methods were applied
      to produce visible-reflected (VIS), ultraviolet-induced visible luminescence
      (UVL), infrared-reflected (IRR), infrared-reflected false colour (IRRFC),
      ultraviolet-reflected (UVR) and ultraviolet-reflected false colour (UVRFC) images
      that provided preliminary indications of the colourants used and their spatial
      distribution. This proved to be an important aid in planning more targeted and
      effective sampling strategies and facilitated comparisons between objects.
      Visible-induced visible luminescence (VIVL) and multiband-reflected (MBR) imaging
      were also explored for the first time with application to textiles, demonstrating
      their potential in mapping red and blue colourants respectively. The physical
      properties observed from all of these images were then related to the more
      detailed information provided by complementary non-invasive techniques, such as
      fibre optic reflectance spectroscopy (FORS), and micro-invasive approaches, such
      as high-performance liquid chromatography mass spectrometry (HPLC-MS). Guidelines
      towards the interpretation of complex MSI images and a discussion of the
      potential and limitations of relating multispectral data to chemical properties
      are presented. An important result of this work is the delineation of a protocol,
      which combines optical microscopy (OM), MSI, FORS and HPLC-MS and shows a high
      degree of potential, not only for the investigation of Late Antique textiles but
      for textiles in museum and historic collections generally.

PMID- 30286140
TI  - miR-125b regulates chemotaxis and survival of bone marrow derived granulocytes in
      vitro and in vivo.
AB  - The evolutionary conserved miR-125b is highly expressed in hematopoietic stem
      cells (HSC) enhancing self-renewal and survival. Accordingly, over-expression of
      miR-125b in HSC may induce myeloproliferative neoplasms and leukemia with long
      latency. During hematopoietic cell maturation miR-125b expression decreases, and
      the function of miR-125b in mature granulocytes is not yet known. We here use
      transplantation of miR-125b over-expressing HSC into syngeneic hosts to generate
      and analyse miR-125b over-expressing granulocytes. Under steady state conditions,
      miR-125b over-expression inhibits granulocytic chemotaxis and LPS- but not PMA-
      and TNFalpha- induced cell death. Inflammatory signals modulate the effects of
      miR-125b over-expression as demonstrated in a sterile peritonitis and a
      polymicrobial sepsis model. In particular, survival of mice with miR-125b over
      expressing granulocytes is significantly reduced as compared to controls in the
      polymicrobial sepsis model. These data demonstrate inflammation dependent effects
      of miR-125b in granulocytes and may point to therapeutic intervention strategies
      in the future.

PMID- 30286141
TI  - Effect of dietary polyunsaturated fatty acid and antioxidant supplementation on
      the transcriptional level of genes involved in lipid and energy metabolism in
      swine.
AB  - Porcine fat traits depend mostly on the interaction between nutritional and
      genetic factors. However, the pathways and biological processes influenced by
      this interaction are still poorly known in pigs, although they can have a huge
      impact on meat quality traits. The present research provides new knowledge
      insight into the effect of four diets (D1 = standard diet; D2 = linseed
      supplementation; D3 = linseed, vitamin E and selenium supplementation; D4 =
      linseed and plant-derived polyphenols supplementation) on the expression of 24
      candidate genes selected for their role in lipid and energy metabolism. The data
      indicated that 10 out of 24 genes were differentially expressed among diets,
      namely ACACA, ADIPOQ, ADIPOR1, CHREBP (MLXPL), ELOVL6, FASN, G6PD, PLIN2, RXRA
      and SCD. Results from the univariate analysis displayed an increased expression
      of ACACA, ADIPOQ, ADIPOR1, CHREBP, ELOVL6, FASN, PLIN2, RXRA and SCD in D4
      compared to D2. Similarly, ACACA, ADIPOQ, ADIPOR1, ELOVL6 and SCD were highly
      expressed in D4 compared to D3, while no differences were observed in D2-D3
      comparison. Moreover, an increased expression of G6PD and ELOVL6 genes in D4
      compared to D1 was observed. Results from the multivariate analysis confirmed
      that D2 was not different from D3 and that ACACA, SCD and FASN expression made D4
      different from D2 and D3. Comparing D4 and D1, the expression levels of ELOVL6
      and ACACA were the most influenced. This research provides evidence that the
      addition of both n-3 PUFA and polyphenols, derived from linseed, grape-skin and
      oregano supplementation in the diets, stimulates the expression of genes involved
      in lipogenesis and in oxidative processes. Results evidenced a greater effect on
      gene expression of the diet added with both plant extracts and n-3 PUFA,
      resulting in an increased expression of genes coding for fatty acid synthesis,
      desaturation and elongation in pig Longissimus thoracis muscle.

PMID- 30286142
TI  - Administration of CORM-2 inhibits diabetic neuropathy but does not reduce
      dyslipidemia in diabetic mice.
AB  - The antinociceptive effects of the carbon monoxide-releasing molecule
      tricarbonyldichlororuthenium (II) dimer (CORM-2) during chronic pain are well
      documented, but most of its possible side-effects remain poorly understood. In
      this work, we examine the impact of CORM-2 treatment on the lipoprotein profile
      and two main atheroprotective functions attributed to high-density lipoprotein
      (HDL) in a mouse model of type 1 diabetes while analyzing the effect of this drug
      on diabetic neuropathy. Streptozotocin (Stz)-induced diabetic mice treated with
      CORM-2 (Stz-CORM-2) or vehicle (Stz-vehicle) were used to evaluate the effect of
      this drug on the modulation of painful diabetic neuropathy using nociceptive
      behavioral tests. Plasma and tissue samples were used for chemical and functional
      analyses, as appropriate. Two main antiatherogenic properties of HDL, i.e., the
      ability of HDL to protect low-density lipoprotein (LDL) from oxidation and to
      promote reverse cholesterol transport from macrophages to the liver and feces in
      vivo (m-RCT), were also assessed. Stz-induced diabetic mice displayed
      hyperglycemia, dyslipidemia and pain hypersensitivity. The administration of 10
      mg/kg CORM-2 during five consecutive days inhibited allodynia and hyperalgesia
      and significantly ameliorated spinal cord markers (Cybb and Bdkrb1expression) of
      neuropathic pain in Stz mice, but it did not reduce the combined dyslipidemia
      shown in Stz-treated mice. Its administration to Stz-treated mice led to a
      significant increase in the plasma levels of cholesterol (~ 1.4-fold vs. Ctrl, ~
      1.3- fold vs. Stz-vehicle; p < 0.05) and was attributed to significant elevations
      in both non-HDL (~ 1.8-fold vs. Ctrl; ~ 1.6-fold vs. Stz-vehicle; p < 0.05) and
      HDL cholesterol (~ 1.3-fold vs. Ctrl, ~ 1.2-fold vs. Stz-vehicle; p < 0.05). The
      increased HDL in plasma was not accompanied by a commensurate elevation in m-RCT
      in Stz-CORM-2 compared to Stz-vehicle mice; instead, it was worsened as revealed
      by decreased [3H]-tracer trafficking into the feces in vivo. Furthermore, the HDL
      mediated protection against LDL oxidation ex vivo shown by the HDL isolated from
      Stz-CORM-2 mice did not differ from that obtained in Stz-vehicle mice. In
      conclusion, the antinociceptive effects produced by a high dose of CORM-2 were
      accompanied by antioxidative effects but were without favorable effects on the
      dyslipidemia manifested in diabetic mice.

PMID- 30286143
TI  - Tumorigenicity-associated characteristics of human iPS cell lines.
AB  - Human induced pluripotent stem cells (hiPSCs) represent promising raw materials
      of human cell-based therapeutic products (hCTPs). As undifferentiated hiPSCs
      exhibit intrinsic tumorigenicity properties that enable them to form teratomas,
      hCTPs containing residual undifferentiated hiPSCs may cause tumor formation
      following transplantation. We first established quantitative and sensitive
      tumorigenicity testing of hiPSCs dissociated into single cells using NOD/Shi-scid
      IL2Rgammanull (NOG) mice by inhibiting apoptosis of hiPSCs with a Rho kinase
      inhibitor. To examine different features in tumorigenicity of various hiPSCs, 10
      commonly available hiPSC lines were subjected to in vivo tumorigenicity testing.
      Transplanted hiPSC lines showed remarkable variation in tumor incidence,
      formation latency, and volumes. Most of the tumors formed were classified as
      immature teratomas. However, no signs of malignancies, such as carcinoma and
      sarcoma, were recognized in the tumors. Characteristics associated tumorigenicity
      of hiPSCs were investigated with microarray analysis, karyotype analysis, and
      whole exome sequencing. Gene expression profiling and pathway analysis supported
      different features of hiPSC lines in tumorigenicity. hiPSC lines showed
      chromosomal abnormalities in some lines and 61-77 variants of cancer-related
      genes carrying effective nonsynonymous mutations, which were confirmed in the
      COSMIC databases. In this study, the chromosomal abnormalities and cancer-related
      gene mutations observed in hiPSC lines did not lead to the malignancy of tumors
      derived from hiPSCs. Our results suggest that the potential tumorigenicity risk
      of hCTPs containing residual undifferentiated hiPSCs is dependent on not only
      amounts of undifferentiated hiPSCs but also features of the cell lines used as
      raw materials, a finding that should be considered from the perspective of
      quality of hCTPs used.

PMID- 30286145
TI  - Tracheal tubes lubricated with water to reduce sore throat after intubation: A
      randomized non-inferiority trial.
AB  - BACKGROUND: Sore throat is common after tracheal intubation. Water can be used to
      lubricate tracheal tubes, but its benefit has not been validated. We thus did a
      randomised non-inferiority trial to test the hypothesis that a tube lubricated
      with water does not reduce sore throat after tracheal intubation. METHODS: We
      randomized female or male patients (n = 296) undergoing surgery in the ears or
      eyes to receive either a tube lubricated with water or a tube without lubrication
      for intubation. We assessed sore throat at 0, 2, 4, and 24 h after surgery;
      pharyngeal injury at 2 and 24 h after surgery; and respiratory infections within
      7 days after surgery. For the incidence of sore throat within 24 h after surgery
      (primary outcome), the two-sided 90% confidence interval of the risk difference
      was compared with the prespecified non-inferiority margin of 15%. Other outcomes
      were analyzed with two-sided superiority tests. RESULTS: The incidence of sore
      throat within 24 h after surgery was 80/147 (54.4%) in the non-lubricated tube
      group and 83/149 (55.7%) in the water-lubricated tube group (risk difference 
      1.3%, 90% confidence interval -10.9% to 8.3%). Because the confidence interval
      was below the non-inferiority margin, the incidence of sore throat was not higher
      in the non-lubricated tube group than in the water-lubricated tube group. There
      was no significant association between groups in the sore throat, pharyngeal
      injury, and respiratory infection at each assessment time. CONCLUSIONS: The tube
      lubricated with water did not reduce sore throat and pharyngeal injury after
      tracheal intubation compared to the tube without lubrication.

PMID- 30286144
TI  - Non-pharmacological interventions for the improvement of post-stroke activities
      of daily living and disability amongst older stroke survivors: A systematic
      review.
AB  - Globally, stroke remains a leading cause of death and disability, with older
      adults disproportionately affected. Numerous non-pharmacological stroke
      rehabilitation approaches are in use to address impairments, but their efficacy
      in older persons is largely unknown. This systematic review examined the evidence
      for such interventions as part of the Optimal Evidence-Based Non-Drug Therapies
      in Older Persons (ONTOP) project conducted under an European Union funded project
      called the Software Engine for the Assessment and Optimisation of Drug and Non
      Drug Therapies in Older Persons (SENATOR) [http://www.senator-project.eu]. A
      Delphi panel of European geriatric experts agreed activities of daily living and
      disability to be of critical importance as stroke rehabilitation outcomes. A
      comprehensive search strategy was developed and five databases (Pubmed, CINAHL,
      Embase, PsycInfo and Cochrane Database of Systematic Reviews) searched for
      eligible systematic reviews. Primary studies meeting our criteria (non
      pharmacologic interventions, involving stroke survivors aged >=65 years,
      assessing activities of daily living and/or disability as outcome) were then
      identified from these reviews. Eligible papers were double reviewed, and due to
      heterogeneity, narrative analysis performed. Cochrane risk of bias and GRADE
      assessment tools were used to assess bias and quality of evidence, allowing us to
      make recommendations regarding specific non-pharmacologic rehabilitation in older
      stroke survivors. In total, 72 primary articles were reviewed spanning 14 types
      of non-pharmacological intervention. Non-pharmacological interventions based on
      physiotherapy and occupational therapy techniques improved activities of daily
      living amongst older stroke survivors. However, no evidence was found to support
      use of any non-pharmacological approach to benefit older stroke survivors'
      disability. Evidence was limited by poor study quality and the small number of
      studies targeting older stroke survivors. We recommend future studies explore
      such interventions exclusively in older adult populations and improve
      methodological and outcome reporting.

PMID- 30286146
TI  - Reward-associated distractors can harm cognitive performance.
AB  - When people carry out cognitive tasks, they sometimes suffer from distractions,
      that is, drops in performance that occur close in time to task-irrelevant
      stimuli. In this research, we examine how the pursuit of rewards contributes to
      distractions. In two experiments, participants performed a math task (in which
      they could earn monetary rewards vs. not) while they were exposed to task
      irrelevant stimuli (that were previously associated with monetary rewards vs.
      not). In Experiment 1, irrelevant cues that were previously associated with
      rewards (vs. not) impaired performance. In Experiment 2, this effect was only
      replicated when these reward-associated distractors appeared relatively early
      during task performance. While the results were thus somewhat mixed, they
      generally support the idea that reward associations can augment the negative
      effect of distractors on performance.

PMID- 30286148
TI  - Judgements of a speaker's personality are correlated across differing content and
      stimulus type.
AB  - It has previously been shown that first impressions of a speaker's personality,
      whether accurate or not, can be judged from short utterances of vowels and
      greetings, as well as from prolonged sentences and readings of complex
      paragraphs. From these studies, it is established that listeners' judgements are
      highly consistent with one another, suggesting that different people judge
      personality traits in a similar fashion, with three key personality traits being
      related to measures of valence (associated with trustworthiness), dominance, and
      attractiveness. Yet, particularly in voice perception, limited research has
      established the reliability of such personality judgements across stimulus types
      of varying lengths. Here we investigate whether first impressions of
      trustworthiness, dominance, and attractiveness of novel speakers are related when
      a judgement is made on hearing both one word and one sentence from the same
      speaker. Secondly, we test whether what is said, thus adjusting content,
      influences the stability of personality ratings. 60 Scottish voices (30 females)
      were recorded reading two texts: one of ambiguous content and one with socially
      relevant content. One word (~500 ms) and one sentence (~3000 ms) were extracted
      from each recording for each speaker. 181 participants (138 females) rated either
      male or female voices across both content conditions (ambiguous, socially
      relevant) and both stimulus types (word, sentence) for one of the three
      personality traits (trustworthiness, dominance, attractiveness). Pearson
      correlations showed personality ratings between words and sentences were strongly
      correlated, with no significant influence of content. In short, when establishing
      an impression of a novel speaker, judgments of three key personality traits are
      highly related whether you hear one word or one sentence, irrespective of what
      they are saying. This finding is consistent with initial personality judgments
      serving as elucidators of approach or avoidance behaviour, without modulation by
      time or content. All data and sounds are available on OSF (osf.io/s3cxy).

PMID- 30286149
TI  - Germ cell desquamation-based testis regression in a seasonal breeder, the
      Egyptian long-eared hedgehog, Hemiechinus auritus.
AB  - Testes of seasonally breeding species experience a severe functional regression
      before the non-breeding period, which implies a substantial mass reduction due to
      massive germ-cell depletion. Two alternative mechanisms of seasonal germ-cell
      depletion have been described in mammals, apoptosis and desquamation (sloughing),
      but their prevalence has not been determined yet due to reduced number of species
      studied. We performed a morphological, hormonal, and molecular study of the
      mechanism of seasonal testicular regression in males of the Egyptian long eared
      hedgehog (Hemiechinus auritus). Our results show that live, non-apoptotic, germ
      cells are massively depleted by desquamation during the testis regression
      process. This is concomitant with both decreased levels of serum testosterone and
      irregular distribution of the cell-adhesion molecules in the seminiferous
      epithelium. The inactive testes maintain some meiotic activity as meiosis onset
      is not halted and spermatocytes die by apoptosis at the pachytene stage. Our data
      support the notion that apoptosis is not the major testis regression effector in
      mammals. Instead, desquamation appears to be a common mechanism in this class.

PMID- 30286147
TI  - Storage fidelity for sequence memory in the hippocampal circuit.
AB  - Episodic memories have been suggested to be represented by neuronal sequences,
      which are stored and retrieved from the hippocampal circuit. A special difficulty
      is that realistic neuronal sequences are strongly correlated with each other
      since computational memory models generally perform poorly when correlated
      patterns are stored. Here, we study in a computational model under which
      conditions the hippocampal circuit can perform this function robustly. During
      memory encoding, CA3 sequences in our model are driven by intrinsic dynamics,
      entorhinal inputs, or a combination of both. These CA3 sequences are hetero
      associated with the input sequences, so that the network can retrieve entire
      sequences based on a single cue pattern. We find that overall memory performance
      depends on two factors: the robustness of sequence retrieval from CA3 and the
      circuit's ability to perform pattern completion through the feedforward
      connectivity, including CA3, CA1 and EC. The two factors, in turn, depend on the
      relative contribution of the external inputs and recurrent drive on CA3 activity.
      In conclusion, memory performance in our network model critically depends on the
      network architecture and dynamics in CA3.

PMID- 30286150
TI  - Imaging & identification of malaria parasites using cellphone microscope with a
      ball lens.
AB  - We have optimized the design and imaging procedures, to clearly resolve the
      malaria parasite in Giemsa-stained thin blood smears, using simple low-cost
      cellphone-based microscopy with oil immersion. The microscope uses a glass ball
      as the objective and the phone camera as the tube lens. Our optimization includes
      the optimal choice of the ball lens diameter, the size and the position of the
      aperture diaphragm, and proper application of immersion, to achieve diagnostic
      capacity in a wide field of view. The resulting system is potentially applicable
      to low-cost in-the-field optical diagnostics of malaria as it clearly resolves
      micron-sized features and allows for analysis of parasite morphology in the field
      of 50 * 50 MUm, and parasite detection in the field of at least 150 * 150 MUm.

PMID- 30286151
TI  - T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes
      proliferation promoted by insulin-like growth factor 1.
AB  - T Cell Leukemia/Lymphoma 1A is expressed during B-cell differentiation and, when
      over-expressed, acts as an oncogene in mouse (Tcl1a) and human (TCL1A) B-cell
      chronic lymphocytic leukemia (B-CLL) and T-cell prolymphocytic leukemia (T-PLL).
      Furthermore, in the murine system Tcl1a is expressed in the ovary, testis and in
      pre-implantation embryos, where it plays an important role in blastomere
      proliferation and in embryonic stem cell (ESC) proliferation and self-renewal. We
      have also observed that Tcl1-/- adult mice exhibit alopecia and deep ulcerations.
      This finding has led us to investigate the role of TCL1 in mouse skin and hair
      follicles. We have found that TCL1 is expressed in the proliferative structure
      (i.e. the secondary hair germ) and in the stem cell niche (i.e. the bulge) of the
      hair follicle during regeneration phase and it is constitutively expressed in the
      basal layer of epidermis where it is required for the correct proliferative
      differentiation program of the keratinocytes (KCs). Taking advantage of the
      murine models we have generated, including the Tcl1-/- and the K14-TCL1
      transgenic mouse, we have analysed the function of TCL1 in mouse KCs and the
      molecular pathways involved. We provide evidence that in the epidermal
      compartment TCL1 has a role in the regulation of KC proliferation,
      differentiation, and apoptosis. In particular, the colony-forming efficiency
      (CFE) and the insulin-like growth factor 1 (IGF1)-induced proliferation are
      dramatically impaired, while apoptosis is increased, in KCs from Tcl1-/- mice
      when compared to WT. Moreover, the expression of differentiation markers such as
      cytokeratin 6 (KRT6), filaggrin (FLG) and involucrin (IVL) are profoundly altered
      in mutant mice (Tcl1-/-). Importantly, by over-expressing TCL1A in basal KCs of
      the K14-TCL1 transgenic mouse model, we observed a significant rescue of cell
      proliferation, differentiation and apoptosis of the mutant phenotype. Finally, we
      found TCL1 to act, at least in part, via increasing phospho-ERK1/2 and decreasing
      phospho-P38 MAPK. Hence, our data demonstrate that regulated levels of Tcl1a are
      necessary for the correct proliferation and differentiation of the
      interfollicular KCs.

PMID- 30286152
TI  - Rapid identification of Bactrocera zonata (Dip.: Tephritidae) using TaqMan real
      time PCR assay.
AB  - Tephritid fruit flies are ranked as one of the most damaging groups of insect
      pests. Morphological identification of fruit flies is mainly performed on adults
      due to the lack of adequate identification keys for immature stages. The peach
      fruit fly, Bactrocera zonata (Saunders), infests some of the principal commercial
      fruits and vegetables. It is, therefore important to avert its global dispersal,
      particularly by accurately identifying this species at ports of entry. In this
      study, a TaqMan real-time polymerase chain reaction (PCR) was developed for the
      accurate identification and sensitive detection of the peach fruit fly. A novel
      set of primers and probe were designed to specifically identify the mitochondrial
      cytochrome oxidase I (COI) gene. All specimens of peach fruit fly (including
      various life stages) were detected, and no cross reactivity with other tested
      tephritids were observed. Since this assay performed equally well with crushed
      insects and purified DNA, we note added efficiency by eliminating DNA extraction
      step. Considering the speed, specificity as well as sensitivity of the assay,
      Taqman real-time PCR can be used as a swift and specific method for pest species
      at ports of entry.

PMID- 30286153
TI  - Incidence and outcome of weaning from mechanical ventilation in medical wards at
      Thammasat University Hospital.
AB  - BACKGROUND: Weaning from mechanical ventilation is classified as simple,
      difficult, or prolonged according to weaning process. Theoretically, simple
      weaning group usually has better clinical outcomes than non-simple group;
      however, the results of previous studies were still inconsistent. OBJECTIVES: The
      purpose of the study was to determine the incidence, predictors, and outcomes of
      ventilator weaning and causes of weaning failure. METHODS: A prospective
      observational study was performed between June and December 2013 in all patients
      (n = 164) who required mechanical ventilation with endotracheal intubation in
      medical wards at Thammasat University Hospital, Thailand. Duration of weaning,
      causes of weaning failure, extubation, reintubation, tracheostomy, number of
      ventilator-free days within 28 days, length of hospital stay, and hospital
      mortality were measured. RESULTS: 103 patients were eligible for final analysis.
      Mean +/- SD age was 65.1+/-17.5 years and 55.3% were males. The incidences of
      simple, difficult and prolonged weaning were 46.6%, 36.9% and 16.5%,
      respectively. The mortality rates for simple, difficult, and prolonged weaning
      were 0%, 10.5% and 23.5% (p = 0.006), respectively. The 3 causes of weaning
      failure in non-simple weaning were bronchospasm, pneumonia, and malnutrition.
      CONCLUSIONS: Non-simple weaning increased mortality. Bronchospasm, pneumonia, and
      malnutrition were key risk factors for weaning failure. Strategies are needed to
      minimize their effects.

PMID- 30286155
TI  - DECORE-21: Assessment of occupational stress in police. Confirmatory factor
      analysis of the original model.
AB  - There is scarce research on stress in Spanish police officers and on the use of
      instruments to assess this construct in this professional group. In Spain, the
      DECORE questionnaire has been one of the most used. Nevertheless, it had not been
      previously applied to police officers. The aim of this study was to analyze both
      the construct validity and the reliability of the original model of 44 items. A
      cross-sectional design and a non-probabilistic quota sampling were used. A total
      of 223 Spanish police officers participated. 202 police personnel were men
      (90.6%) and 21 were women (9.4%). The average age was 41 years old (SD = 7.52).
      These police officers answered the DECORE questionnaire. Confirmatory Factor
      Analysis was carried out. The results showed an unsatisfactory adjustment using
      the original model of 44 items. A final solution of 21 items and four factors was
      formulated with both suitable validity and reliability indexes. In this model, 23
      items that did not weigh highly in any of the four factors were removed. The
      DECORE-21 questionnaire is recommended to assess work-related stress in police
      officers.

PMID- 30286154
TI  - BRCA1/2 mutations are not a common cause of malignant melanoma in the Polish
      population.
AB  - The association of BRCA1/2 mutations with melanoma is not completely determined;
      the interpretation of variants of unknown significance is also problematic. To
      evaluate these issues we explored the molecular basis of melanoma risk by
      performing whole-exome sequencing on a cohort of 96 unrelated Polish early-onset
      melanoma patients and targeted sequencing of BRCA1/2 genes on additional 30
      melanoma patients with familial aggregation of breast and other cancers.
      Sequencing was performed on peripheral blood. We evaluated MutationTaster,
      Polyphen2, SIFT, PROVEAN algorithms, analyzed segregation with cancer disease (in
      both families with identified BRCA2 variants) and in one family performed LOH
      (based on 2 primary tumors). We found neither pathogenic mutations nor variants
      of unknown significance within BRCA1. We identified two BRCA2 variants of unknown
      significance: c.9334G>A and c.4534 C>T. Disease allele frequency was evaluated by
      genotyping of 1230 consecutive melanoma cases, 5000 breast cancer patients, 3500
      prostate cancers and 9900 controls. Both variants were found to be absent among
      unselected cancer patients and healthy controls. The MutationTaster, Polyphen2
      and SIFT algorithms indicate that c.9334G>A is a damaging variant. Due to lack of
      tumour tissue LOH analysis could not be performed for this variant. The variant
      segregated with the disease. The c.4534 C>T variant did not segregate with
      disease, there was no LOH of the variant. The c.9334G>A variant, classified as a
      rare variant of unknown significance, on current evidence may predisposes to
      cancers of the breast, prostate and melanoma. Functional studies to describe how
      the DNA change affects the protein function and a large multi-center study to
      evaluate its penetrance are required.

PMID- 30286156
TI  - Application of insulin signaling to predict insect growth rate in Maruca vitrata
      (Lepidoptera: Crambidae).
AB  - Insect growth is influenced by two major environmental factors: temperature and
      nutrient. These environmental factors are internally mediated by insulin/insulin
      like growth factor signal (IIS) to coordinate tissue or organ growth. Maruca
      vitrata, a subtropical lepidopteran insect, migrates to different climate regions
      and feeds on various crops. The objective of this study was to determine
      molecular tools to predict growth rate of M. vitrata using IIS components. Four
      genes [insulin receptor (InR), Forkhead Box O (FOXO), Target of Rapamycin (TOR),
      and serine-threonine protein kinase (Akt)] were used to correlate their
      expression levels with larval growth rates under different environmental
      conditions. The functional association of IIS and larval growth was confirmed
      because RNA interference of these genes significantly decreased larval growth
      rate and pupal weight. Different rearing temperatures altered expression levels
      of these four IIS genes and changed their growth rate. Different nutrient
      conditions also significantly changed larval growth and altered expression levels
      of IIS components. Different local populations of M. vitrata exhibited
      significantly different larval growth rates under the same nutrient and
      temperature conditions along with different expression levels of IIS components.
      Under a constant temperature (25 degrees C), larval growth rates showed
      significant correlations with IIS gene expression levels. Subsequent regression
      formulas of expression levels of four IIS components against larval growth rate
      were applied to predict growth patterns of M. vitrata larvae reared on different
      natural hosts and natural local populations reared on the same diet. All four
      formulas well predicted larval growth rates with some deviations. These results
      indicate that the IIS expression analysis explains the growth variation at the
      same temperature due to nutrient and genetic background.

PMID- 30286157
TI  - Social network properties predict chronic aggression in commercial pig systems.
AB  - Post-mixing aggression in pigs is a harmful and costly behaviour which negatively
      impacts both animal welfare and farm efficiency. There is vast unexplained
      variation in the amount of acute and chronic aggression that dyadic behaviours do
      not fully explain. This study hypothesised that certain pen-level network
      properties may improve prediction of lesion outcomes due to the incorporation of
      indirect social interactions that are not captured by dyadic traits. Utilising
      current SNA theory, we investigate whether pen-level network properties affect
      the number of aggression-related injuries at 24 hours and 3 weeks post-mixing
      (24hr-PM and 3wk-PM). Furthermore we compare the predictive value of network
      properties to conventional dyadic traits. A total of 78 pens were video recorded
      for 24hr post-mixing. Each aggressive interaction that occurred during this time
      period was used to construct the pen-level networks. The relationships between
      network properties at 24hr and the pen level injuries at 24hr-PM and 3wk-PM were
      analysed using mixed models and verified using permutation tests. The results
      revealed that network properties at 24hr could predict long term aggression (3wk
      PM) better than dyadic traits. Specifically, large clique formation in the first
      24hr-PM predicted fewer injuries at 3wk-PM and high betweenness centralisation at
      24hr-PM predicted increased rates of injury at 3wk-PM. This study demonstrates
      that network properties present during the first 24hr-PM have predictive value
      for chronic aggression, and have potential to allow identification and
      intervention for at risk groups.

PMID- 30286158
TI  - Isotope values of the bioavailable strontium in inland southwestern Sweden-A
      baseline for mobility studies.
AB  - The inland area of southwestern Sweden is well known for its well-preserved
      archaeological animal and human remains dating back to the Mesolithic and
      Neolithic (10000-4000 and 4000-1700 BC). They allow application of multiple
      bioarchaeological methods, giving insights into various and complementary aspects
      of prehistoric human life, as well as economic and social structures. One
      important aspect concerns human mobility and its relation to social networks and
      to circulation of objects. Here, strontium isotope analysis plays a crucial role.
      The present study aims to construct a strontium isotope baseline of southwestern
      Sweden with considerably greater coverage and higher resolution than previously
      published data. As the region has been affected by glacial events, the relation
      between bedrock geology and isotope signals of the bioavailable strontium in such
      areas is given special attention. We determined strontium isotope ratios for 61
      water and five archaeological animal samples, and combined the data with previous
      measurements of two water and 21 non-domestic faunal samples. The results reveal
      a complex pattern. Several areas with distinct baseline ranges can be
      distinguished, although with overlaps between some of them. Overall, the
      bioavailable strontium isotope signals mirror the basement geology of the region.
      The highest ratios occur in the geologically oldest eastern parts of the
      Precambrian terrain, while lower ratios are found in the western part, and the
      lowest ratios occur in the youngest Paleozoic areas. At the same time, there are
      minor deviations compared to the underlying bedrock, due to glacial transport,
      overlying sediments, and local intrusions of younger rocks. The background data
      set now available allows for more nuanced and detailed interpretations of human
      and animal mobility in the region, in particular by identification of subregions
      with differing strontium isotope ratios within the Precambrian province. Also, we
      can now identify long distance mobility with greater confidence.

PMID- 30286159
TI  - Impact of pre-existing treatment with statins on the course and outcome of tick
      borne encephalitis.
AB  - OBJECTIVES: Although statins have anti-inflammatory and potentially also
      antimicrobial (including antiviral) activity, their therapeutic impact on
      infectious diseases is controversial. In this study, we evaluated whether pre
      existing statin use influenced the course and outcome of tick-borne encephalitis.
      METHODS: To assess the influence of statin usage on the severity of acute illness
      and the outcome of tick-borne encephalitis, univariate and multivariable analyses
      were performed for 700 adult patients with tick-borne encephalitis of whom 77
      (11%) were being treated with statins, and for 410 patients of whom 53 (13%) were
      receiving statins, respectively. RESULTS: Multivariable analyses found no
      statistically significant association between statin usage and having a milder
      acute illness. There was also no statistically significant benefit with respect
      to a favorable outcome defined by the absence of post-encephalitic syndrome (ORs
      for a favorable outcome at 6 months was 0.96, 95% CI: 0.46-2.04, P = 0.926; at 12
      months 0.29, 95% CI: 0.06-1.33, P = 0.111; at 2-7 years after acute illness 0.44,
      95% CI: 0.09-2.22, P = 0.321), by a reduction in the frequency of six nonspecific
      symptoms (fatigue, myalgia/arthralgia memory disturbances, headache,
      concentration disturbances, irritability) occurring during the 4 week period
      before the last examination, or by higher SF-36 scores in any of the eight
      separate domains of health as well as in the physical and mental global overall
      component. Furthermore, there were no significant differences between patients
      receiving statins and those who were not in the cerebrospinal fluid or serum
      levels for any of the 24 cytokines/chemokines measured. CONCLUSIONS: In this
      observational study, we could not prove that pre-existing use of statins affected
      either the severity of the acute illness or the long-term outcome of tick-borne
      encephalitis.

PMID- 30286160
TI  - HIV-1C proviral DNA for detection of drug resistance mutations.
AB  - BACKGROUND: Using HIV proviral DNA as a template may be suitable for initial
      detection of transmitted drug resistance mutations (TDRMs) as it is easy to
      handle and less expensive compared to RNA. However, existing literatures which
      are mainly focused on HIV-1B subtypes DNA extracted from PBMCs revealed
      controversial findings ranging from the detection of significantly lower or
      higher mutations in proviral DNA compared to historic viral RNA. Thus, to verify
      whether viral RNA or proviral DNA has improved sensitivity in detecting
      transmitted genotypic drug resistance mutations paired viral RNA and proviral DNA
      (which is directly extracted from stored whole blood) samples were tested from
      Ethiopian antiretroviral naive HIV-1C infected subjects. METHODS: In the present
      comparative study the frequency of TDR mutations was assessed in paired samples
      of viral RNA and proviral DNA (extracted directly from stored whole blood) of HIV
      1C infected treatment naive patients and interpreted using the 2009 WHO drug
      resistance surveillance mutation lists, Stanford University drug resistance data
      base and International Antiviral Society-USA mutation lists. RESULTS: High
      agreement in rate of TDR between the two compartments was observed using the WHO
      mutation lists. While mutations G190A and E138A were concurrently found in both
      compartments, others such as G73S on PR and A62V, M184I, M230I on RT were
      identified in proviral DNA only. All signature mutations seen in viral RNA were
      not missed in proviral DNA. CONCLUSIONS: The concordance of major genotype drug
      resistance mutation between RNA and proviral DNA in treatment naive patients
      suggests that proviral DNA might be an alternative approaches for an initial
      assessment of drug resistance prior to initiation of antiretroviral therapy using
      the WHO mutations lists in resource-limited countries. However, the clinical
      importance of TDRMs observed only in proviral DNA in terms of being a risk factor
      for virologic failure and whether they limit future treatment options needs
      additional investigation using more sensitive sequencing approaches such as Next
      Generation Sequencing (NGS).

PMID- 30286161
TI  - Understanding women's, caregivers', and providers' experiences with home-based
      records: A systematic review of qualitative studies.
AB  - Mothers, caregivers, and healthcare providers in 163 countries have used paper
      and electronic home-based records (HBRs) to facilitate primary care visit. These
      standardized records have the potential to empower women, improve the quality of
      care for mothers and children and reduce health inequities. This review examines
      experiences of women, caregivers and providers with home-based records for
      maternal and child health and seeks to explore the feasibility, acceptability,
      affordability and equity of these interventions. We systematically searched
      MEDLINE, MEDLINE In-Process, MEDLINE Ahead of Print, Embase, CINAHL, ERIC, and
      PsycINFO for articles that were published between January 1992 and December 2017.
      We used the CASP checklist to assess study quality, a framework analysis to
      support synthesis, and GRADE-CERQual to assess the confidence in the key
      findings. Of 7,904 citations, 19 studies met our inclusion criteria. In these
      studies, mothers, caregivers and children shared HBR experiences in relation to
      maternal and child health which facilitated the monitoring of immunisations and
      child growth and development. Participants' reports of HBRs acting as a point of
      commonality between patient and provider offer an explanation for their
      perceptions of improved communication and patient-centered care, and enhanced
      engagement and empowerment during pregnancy and childcare. Healthcare providers
      and nurses reported that the home-based record increased their feeling of
      connection with their patients. Although there were concerns around electronic
      records and confidentiality, there were no specific concerns reported for paper
      records. Mothers and other caregivers see home based records as having a pivotal
      role in facilitating primary care visits and enhancing healthcare for their
      families. The records' potential could be limited by users concerns over
      confidentiality of electronic home-based records, or shortcomings in their
      design. Health systems should seize the opportunity HBRs provide in empowering
      women, especially in the contexts of lower literacy levels and weak health care
      delivery systems.

PMID- 30286162
TI  - Functional analysis of a triplet deletion in the gene encoding the sodium glucose
      transporter 3, a potential risk factor for ADHD.
AB  - Sodium-glucose transporters (SGLT) belong to the solute carrier 5 family, which
      is characterized by sodium dependent transport of sugars and other solutes. In
      contrast, the human SGLT3 (hSGLT3) isoform, encoded by SLC5A4, acts as a glucose
      sensor that does not transport sugar but induces membrane depolarization by Na+
      currents upon ligand binding. Whole-exome sequencing (WES) of several extended
      pedigrees with high density of attention-deficit/hyperactivity disorder (ADHD)
      identified a triplet ATG deletion in SLC5A4 leading to a single amino acid loss
      (DeltaM500) in the hSGLT3 protein imperfectly co-segregating with the clinical
      phenotype of ADHD. Since mutations in homologous domains of hSGLT1 and hSGLT2
      were found to affect intestinal and renal function, respectively, we analyzed the
      functional properties of hSGLT3[wt] and [DeltaM500] by voltage clamp and current
      clamp recordings from cRNA-injected Xenopus laevis oocytes. The cation
      conductance of hSGLT3[wt] was activated by application of glucose or the specific
      agonist 1-desoxynojirimycin (DNJ) as revealed by inward currents in the voltage
      clamp configuration and cell depolarization in the current clamp mode. Almost no
      currents and changes in membrane potential were observed when glucose or DNJ were
      applied to hSGLT3[DeltaM500]-injected oocytes, demonstrating a loss of function
      by this amino acid deletion in hSGLT3. To monitor membrane targeting of wt and
      mutant hSGLT3, fusion constructs with YFP were generated, heterologously
      expressed in Xenopus laevis oocytes and analyzed for membrane fluorescence by
      confocal microscopy. In comparison to hSGLT3[wt] the fluorescent signal of mutant
      [DeltaM500] was reduced by 43% indicating that the mutant phenotype might mainly
      result from inaccurate membrane targeting. As revealed by homology modeling,
      residue M500 is located in TM11 suggesting that in addition to the core structure
      (TM1-TM10) of the transporter, the surrounding TMs are equally crucial for
      transport/sensor function. In conclusion, our findings indicate that the deletion
      [DeltaM500] in hSGLT3 inhibits membrane targeting and thus largely disrupts
      glucose-induced sodium conductance, which may, in interaction with other ADHD
      risk-related gene variants, influence the risk for ADHD in deletion carriers.

PMID- 30286163
TI  - Fas/FasL pathway and cytokines in keratinocytes in atopic dermatitis -
      Manipulation by the electromagnetic field.
AB  - BACKGROUND: Atopic dermatitis (AD) is one of the most frequent skin diseases.
      Changes of the keratinocytes functionality play a major role in the development
      of AD. For example, activation of the Fas (CD95)/FasL (CD178) pathway in AD does
      not lead to extensive apoptosis in skin. Binding of the Fas receptor to its
      protein ligand-FasL, which are present on the (AD)-modified keratinocytes, should
      result in the sequential induction of cell death, but there is no evidence of
      extensive apoptosis of these cells. This suggests that non-apoptotic mechanism of
      Fas/FasL pathway is commonly encountered, although not examined in the case of
      AD, phenomenon. An electromagnetic field, which was used to influence cultured
      cells in this study, can modulate proliferation, apoptosis, differentiation, and
      metabolism in various cells. OBJECTIVE: Here, we evaluate the possibility to
      manipulate the immune activation of AD keratinocytes and their response to the
      electromagnetic field, which was not tested before. METHODS: Keratinocytes
      isolated from the skin of healthy subjects (n = 20) and patients with atopic
      dermatitis (n = 20) as well as HaCaT and PCS-200-010 cell were exposed to the 900
      MHz electromagnetic field for 60 minutes. Cytometric analysis of viability,
      Fas/FasL, p-ERK, p-p38 and p-JNK expression and Luminex analysis of cytokine
      concentration were performed in two-time points: 4 and 24 hours after the
      exposition. RESULTS: This research has shown upregulated Fas, FasL, p-ERK, p-p38,
      and p-JNK expression along with increased cytokine secretion (IL-1beta, IL-4, IL
      8, IL-10, IL-12p70, IL-13, IL-17A, IL-31 and TNFalpha) by keratinocytes derived
      from the skin of patients with the AD when compared with healthy control.
      Exposure of keratinocyte cultures obtained from AD patients to EMF resulted in a
      decrease of 1beta, IL-4, IL-10, IL-12, I L-13, IL-17, IL-31 and TNFalpha levels.
      Keratinocytes derived from the skin of AD patients are characterized by elevated
      Fas and FasL expression when compared to healthy control. CONCLUSION: Apoptotic
      and nonapoptotic activation of the Fas/FasL-dependent signaling pathway may play
      a significant role in the pathogenesis of AD, by adjusting the local cytokine and
      chemokine environment at the site of inflammation. Moreover, the electromagnetic
      field exhibits strong immunomodulatory effects on AD-modified keratinocytes.

PMID- 30286164
TI  - Correction: Crystal structure of the C-terminal four-helix bundle of the
      potassium channel KCa3.1.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0199942.].

PMID- 30286165
TI  - Efficient multi-task chemogenomics for drug specificity prediction.
AB  - Adverse drug reactions, also called side effects, range from mild to fatal
      clinical events and significantly affect the quality of care. Among other causes,
      side effects occur when drugs bind to proteins other than their intended target.
      As experimentally testing drug specificity against the entire proteome is out of
      reach, we investigate the application of chemogenomics approaches. We formulate
      the study of drug specificity as a problem of predicting interactions between
      drugs and proteins at the proteome scale. We build several benchmark datasets,
      and propose NN-MT, a multi-task Support Vector Machine (SVM) algorithm that is
      trained on a limited number of data points, in order to solve the computational
      issues or proteome-wide SVM for chemogenomics. We compare NN-MT to different
      state-of-the-art methods, and show that its prediction performances are similar
      or better, at an efficient calculation cost. Compared to its competitors, the
      proposed method is particularly efficient to predict (protein, ligand)
      interactions in the difficult double-orphan case, i.e. when no interactions are
      previously known for the protein nor for the ligand. The NN-MT algorithm appears
      to be a good default method providing state-of-the-art or better performances, in
      a wide range of prediction scenario that are considered in the present study:
      proteome-wide prediction, protein family prediction, test (protein, ligand) pairs
      dissimilar to pairs in the train set, and orphan cases.

PMID- 30286166
TI  - Methodological considerations in clinical outcomes assessment of pharmacy-based
      minor ailments management: A systematic review.
AB  - BACKGROUND: The accessibility of services within community pharmacies provides an
      ideal opportunity to manage minor ailments, yet over L1.1 billion is spent by the
      National Health Service (NHS) in the United Kingdom (UK) in managing minor
      ailments in high cost settings. There is a need to review the evidence base
      around clinical effectiveness of pharmacy-based management of minor ailments
      since the absence of such may lead to under-utilisation of pharmacy services and
      non-implementation of available pharmacy service models. This study aimed to
      systematically review the methodological approaches used to assess clinical
      outcomes of pharmacy-based management of minor ailments in the research
      literature. METHODS: A systematic review was conducted to identify relevant
      literature using the following databases: Medline, EMBASE, CINAHL, IPA, CRD,
      CDSR, and Google Scholar from publication year 2000 onwards. Studies were
      included if they evaluated clinical outcomes of pharmacy-based management of any
      minor ailments, with or without a comparator setting such as Emergency
      Departments (EDs) or general practices. Screening and selection of titles,
      abstracts and full texts followed by data extraction and quality assessment (QA)
      was conducted. Paired researchers, from the team, reviewed papers using a
      protocol based on the Preferred Reporting Items for Systematic Review and Meta
      Analysis Protocols (PRISMA-P). QA was undertaken using the Critical Appraisal
      Skills Programme (CASP). Reporting was conducted in accordance with PRISMA
      checklist and statements. RESULTS: A total of 19 studies were included. The
      majority of studies were observational, conducted in community pharmacies, and
      did not use a comparator participant group nor a comparator setting.
      Interventions included counselling, medicines supply and provision of advice on
      the management of minor ailments. One study used the randomised controlled trial
      (RCT) design with majority of the study utilising observational design. A range
      of clinical outcomes including symptom severity, pattern, resolution, and quality
      of life were reported. Methods used for the assessment of clinical outcomes were,
      overall, poorly reported. This included a lack of information on the development
      and validation of the data collection tools and the timing of baseline and follow
      up data collection. Adverse clinical outcomes data were collected by only seven
      studies. CONCLUSIONS: Currently, there are methodological limitations in the
      studies that have sought to assess clinical outcomes of pharmacy-based management
      of minor ailments. Such lack of high quality evidence may contribute to failings
      to shift care from high cost settings, such as EDs and general practices.
      Generation of high quality evidence is likely to influence public choices when
      seeking care for minor ailments. There is scope for development of a core
      outcomes set specific to minor ailments management and development of a validated
      methodology for measuring such outcomes in a research study.

PMID- 30286167
TI  - 4.1Ba is necessary for glutamatergic synapse formation in the sensorimotor
      circuit of developing zebrafish.
AB  - During the process of synapse formation, thousands of proteins assemble at
      prospective sites of cell-cell communication. Although many of these proteins
      have been identified, the roles they play in generating functional connections
      during development remain unknown. 4.1 scaffolding proteins have been implicated
      in synapse formation and maturation in vitro, but in vivo studies for some family
      members have suggested these proteins are not important for this role. We
      examined the role of family member 4.1B because it has been implicated in
      glutamatergic synaptogenesis, but has not been described in vivo. We identified
      two 4.1B genes in zebrafish, 4.1Ba and 4.1Bb, by sequence comparisons and synteny
      analysis. In situ hybridization shows these genes are differentially expressed,
      with 4.1Ba expressed primarily in the nervous system and 4.1Bb expressed in the
      nervous system and muscle, but not the spinal cord. We focused our studies on
      4.1Ba in the spinal cord. 4.1Ba knockdown reduced the number of glutamatergic
      synapses at caudal primary motor neurons and caused an increase in the duration
      of touch-evoked coiling. These results suggest 4.1Ba is important for the
      formation of functional glutamatergic synapses in the developing zebrafish spinal
      cord.

PMID- 30286168
TI  - Fractional integral-like processing in retinal cones reduces noise and improves
      adaptation.
AB  - In the human retina, rod and cone cells detect incoming light with a molecule
      called rhodopsin. After rhodopsin molecules are activated (by photon impact),
      these molecules activate the rest of the signalling process for a brief period of
      time until they are deactivated by a multistage process. First, active rhodopsin
      is phosphorylated multiple times. Following this, they are further inhibited by
      the binding of molecules called arrestins. Finally, they decay into opsins. The
      time required for each of these stages becomes progressively longer, and each
      stage further reduces the activity of rhodopsin. However, while this deactivation
      process itself is well researched, the roles of the above stages in signal (and
      image) processing are poorly understood. In this paper, we will show that the
      activity of rhodopsin molecules during the deactivation process can be described
      as the fractional integration of an incoming signal. Furthermore, we show how
      this affects an image; specifically, the effect of fractional integration in
      video and signal processing and how it reduces noise and the improves
      adaptability under different lighting conditions. Our experimental results
      provide a better understanding of vertebrate and human vision, and why the rods
      and cones of the retina differ from the light detectors in cameras.

PMID- 30286169
TI  - Correction: Analytical Sensitivity Comparison between Singleplex Real-Time PCR
      and a Multiplex PCR Platform for Detecting Respiratory Viruses.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0143164.].

PMID- 30286170
TI  - Effect of fenofibrate in 1113 patients at low-density lipoprotein cholesterol
      goal but high triglyceride levels: Real-world results and factors associated with
      triglyceride reduction.
AB  - Fibrates are used in patients with dyslipidemia and high cardiovascular risk.
      However, information regarding drug response to fibrate has been highly limited.
      We investigated treatment results and factors associated with triglyceride
      reduction after fenofibrate therapy using large-scale real-world data. Patients
      with one or more cardiovascular risk factors, at low-density lipoprotein
      cholesterol goal but with triglyceride level >=150 mg/dL, and undergoing
      treatment with fenofibrate 135-160 mg for the first time were included in this
      retrospective observational study. The outcome variable was the percentage
      changes of TG levels. The achievement rate of triglyceride <150 mg/dL was
      additionally analyzed. Factors associated with treatment results were also
      analyzed. Among 2546 patients who were initially screened, 1113 patients were
      enrolled (median age: 61 years; male: 71%). After median follow-up of 4 months,
      the median change in triglyceride was -60%, and 49% of the patients reached
      triglyceride <150 mg/dL. After adjusting for confounding variables, female sex,
      non-diabetic status, coronary artery disease, lower baseline triglyceride, and no
      statin use were identified to be independently associated with achievement of
      triglyceride <150 mg/dL. Among them, female sex, non-diabetic status, and
      coronary artery disease were also related to median or greater percentage
      reduction of triglyceride. In conclusion, only half of the study patients reached
      triglyceride levels <150 mg/dL after real-world fenofibrate therapy. This study
      indicates that more attention is needed on some subgroups to obtain optimal
      triglyceride levels when treating with fenofibrate.

PMID- 30286171
TI  - The translation, validity and reliability of the German version of the Fremantle
      Back Awareness Questionnaire.
AB  - BACKGROUND: The Fremantle Back Awareness Questionnaire (FreBAQ) claims to assess
      disrupted self-perception of the back. The aim of this study was to develop a
      German version of the FreBAQ (FreBAQ-G) and assess its test-retest reliability,
      its known-groups validity and its convergent validity with another purported
      measure of back perception. METHODS: The FreBaQ-G was translated following
      international guidelines for the transcultural adaptation of questionnaires.
      Thirty-five patients with non-specific CLBP and 48 healthy participants were
      recruited. Assessor one administered the FreBAQ-G to each patient with CLBP on
      two separate days to quantify intra-observer reliability. Assessor two
      administered the FreBaQ-G to each patient on day 1. The scores were compared to
      those obtained by assessor one on day 1 to assess inter-observer reliability.
      Known-groups validity was quantified by comparing the FreBAQ-G score between
      patients and healthy controls. To assess convergent validity, patient's FreBAQ-G
      scores were correlated to their two-point discrimination (TPD) scores. RESULTS:
      Intra- and Inter-observer reliability were both moderate with ICC3.1 = 0.88
      (95%CI: 0.77 to 0.94) and 0.89 (95%CI: 0.79 to 0.94), respectively. Intra- and
      inter-observer limits of agreement (LoA) were 6.2 (95%CI: 5.0-8.1) and 6.0 (4.8
      7.8), respectively. The adjusted mean difference between patients and controls
      was 5.4 (95%CI: 3.0 to 7.8, p<0.01). Patient's FreBAQ-G scores were not
      associated with TPD thresholds (Pearson's r = -0.05, p = 0.79). CONCLUSIONS: The
      FreBAQ-G demonstrated a degree of reliability and known-groups validity.
      Interpretation of patient level data should be performed with caution because the
      LoA were substantial. It did not demonstrate convergent validity against TPD.
      Floor effects of some items of the FreBAQ-G may have influenced the validity and
      reliability results. The clinimetric properties of the FreBAQ-G require further
      investigation as a simple measure of disrupted self-perception of the back before
      firm recommendations on its use can be made.

PMID- 30286172
TI  - Doctor's recommendations for psychosocial care: Frequency and predictors of
      recommendations and referrals.
AB  - BACKGROUND: A significant number of oncological patients are heavily burdened by
      psychosocial stress. Doctors recommending or referring their patients to psycho
      oncologists in the course of routine consultations can positively influence
      psycho-oncological care. The aim of this study was to analyze the frequency and
      predictors of such recommendations and to examine the use of these services by
      patients. METHODS: 4,020 cancer patients (mean age 58 years; 51% women) were
      evaluated in a multicenter, cross-sectional study in Germany. Data was gathered
      about doctors' referral practices, patients' utilization of psycho-oncological
      care services, and disease-related symptoms. The PHQ-9 depression scale and the
      GAD-7 anxiety scale were used to measure psychological burden. Descriptive data
      analysis was conducted on the basis of subgroup comparisons and multivariable
      analysis was done using binary logistical regression. RESULTS: 21.9% of the
      respondents reported having been given a recommendation or referral for psycho
      oncological care by a doctor within the course of their cancer diagnosis and
      treatment. This comprises 29.5% of the patients identified by screening as being
      psychologically burdened. Nearly half of the patients who received a
      recommendation or referral (49.8%) acted on it. Predictors for seeking out psycho
      oncological care included: patient desire (OR = 2.0), previous experience with
      psycho-oncological care (OR = 1.59), and female gender (OR = 1.57). Multivariable
      analysis indicated that patients' level of psychological burden (depression,
      anxiety) had no effect on whether doctors gave them a recommendation or referral.
      CONCLUSIONS: Along with examining the degree to which patients are burdened (e.g.
      using screening instruments), determining whether or not patients would like to
      receive psycho-oncological care is an important aspect of improving referral
      practices and, by extension, will allow important progress in the field of psycho
      oncological care to be made.

PMID- 30286174
TI  - Correction: Light correlated color temperature and task switching performance in
      preschool-age children: Preliminary insights.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0202973.].

PMID- 30286173
TI  - Microbial enrichment and gene functional categories revealed on the walls of a
      spent fuel pool of a nuclear power plant.
AB  - Microorganisms developing in the liner of the spent fuel pool (SFP) and the fuel
      transfer channel (FTC) of a Nuclear Power Plant (NPP) can form high radiation
      resistant biofilms and cause corrosion. Due to difficulties and limitations to
      obtain large samples from SFP and FTC, cotton swabs were used to collect the
      biofilm from the wall of these installations. Molecular characterization was
      performed using massively parallel sequencing to obtain a taxonomic and
      functional gene classification. Also, samples from the drainage system were
      evaluated because microorganisms may travel over the 12-meter column of the pool
      water of the Brazilian Nuclear Power Plant (Angra1), which has been functioning
      since 1985. Regardless of the treatment of the pool water, our data reveal the
      unexpected presence of Fungi (Basidiomycota and Ascomycota) as the main
      contaminators of the SFP and FTC. Ustilaginomycetes (Basidiomycota) was the major
      class contributor (70%) in the SFP and FTC reflecting the little diversity in
      these sites; nevertheless, Proteobacteria, Actinobacteria, Firmicutes (Bacilli)
      were present in small proportions. Mapping total reads against six fungal
      reference genomes indicate that there is, in fact, a high abundance of fungal
      sequences in samples collected from SFP and FTC. Analysis of the ribosomal
      internal transcribed spacer (ITS) 1 and 2 regions and the protein found in the
      mitochondria of eukaryotic cells, cytochrome b (cytb) grouped our sample fungi in
      the clade 7 as Ustilago and Pseudozyma. In contrast, in the drainage system,
      Alphaproteobacteria were present in high abundances (55%). The presence of
      Sphingopyxis, Mesorhizobium, Erythrobacter, Sphingomonas, Novosphingobium,
      Sphingobium, Chelativorans, Oceanicaulis, Acidovorax, and Cyanobacteria was
      observed. Based on genomic annotation data, the assessment of the biological
      function found a higher proportion of protein-coding sequences related to
      respiration and protein metabolism in SFP and FTC samples. The knowledge of this
      biological inventory present in the system may contribute to further studies of
      potential microorganisms that might be useful for bioremediation of nuclear
      waste.

PMID- 30286175
TI  - The Daily Mile: What factors are associated with its implementation success?
AB  - BACKGROUND: Despite the known benefits of a physically active lifestyle, there
      are few examples of interventions that have been successfully implemented at a
      population level over a long period of time. One such example is The Daily Mile,
      a school based physical activity initiative, where a teacher takes their class
      out daily during class time for a short bout of ambulatory activity. At one
      school, this activity appears has been sustained over a long period (6 years),
      has the whole school participating and is now incorporated into its daily
      routine. The aim of this paper was to understand how The Daily Mile was
      implemented in primary schools and to assess factors associated with its
      successful implementation. METHODS: Semi-structured interviews with school staff
      who had a significant role in implementing The Daily Mile were conducted at four
      primary schools in central Scotland. Interviews were digitally recorded and
      transcribed verbatim. Data were analysed using thematic analysis and descriptive
      analysis and interpretation of data undertaken. Details regarding the school
      grounds and facilities were also noted during the interviews. RESULTS: Having
      simple core intervention components, flexible delivery that supports teacher
      autonomy and being adaptable to suit the specific primary school context appear
      to be key aspects of The Daily Mile that are related to its implementation
      success. Other factors relating to how The Daily Mile was developed, trialled and
      rolled out might also have contributed towards its successful implementation.
      CONCLUSION: The Daily Mile appears to have several factors which may relate to
      its implementation success. These are important considerations for others looking
      to implement The Daily Mile effectively in their primary school or in other
      contexts.

PMID- 30286176
TI  - Synthetic viruses-Anything new?

PMID- 30286177
TI  - Identification of KLF9 and BCL3 as transcription factors that enhance
      reprogramming of primordial germ cells.
AB  - Primordial germ cells (PGCs) are precursors of eggs and sperm. Although PGCs are
      unipotent cells in vivo, they are reprogrammed into pluripotent stem cells
      (PSCs), also known as embryonic germ cells (EGCs), in the presence of leukemia
      inhibitory factor and basic fibroblast growth factor (bFGF) in vitro. However,
      the molecular mechanisms responsible for their reprogramming are not fully
      understood. Here we show identification of transcription factors that mediate PGC
      reprogramming. We selected genes encoding transcription factors or epigenetic
      regulatory factors whose expression was significantly different between PGCs and
      PSCs with in silico analysis and RT-qPCR. Among the candidate genes, over
      expression (OE) of Bcl3 or Klf9 significantly enhanced PGC reprogramming.
      Notably, EGC formation was stimulated by Klf9-OE even without bFGF. G-protein
      coupled receptor signaling-related pathways, which are involved in PGC
      reprogramming, were enriched among genes down-regulated by Klf9-OE, and forskolin
      which activate adenylate cyclase, rescued repressed EGC formation by knock-down
      of Klf9, suggesting a molecular linkage between KLF9 and such signaling.

PMID- 30286179
TI  - Horsepox and the need for a new norm, more transparency, and stronger oversight
      for experiments that pose pandemic risks.

PMID- 30286178
TI  - Organochlorine pesticides, polybrominated diphenyl ethers and polychlorinated
      biphenyls in surficial sediments of the Awash River Basin, Ethiopia.
AB  - This study was initiated to document information on the levels of sediment
      contamination with organochlorine pesticides (OCPs), polychlorinated biphenyls
      (PCBs) and polybrominated diphenyl ethers (PBDEs). Moreover, it was intended to
      identify compounds which impose major ecological risks to aquatic organisms.
      Surficial sediments were collected from 46 locations within the streams and
      rivers of the Awash River Basin. In total 30 compounds were included in this
      study: 16 OCPs, 7 PCBs and 7 PBDEs. The total concentrations of OCPs, PCBs, and
      PBDEs ranged from 6.63 to 206.13 ng g-1- dry weight (dw), 0.85 to 26.56 ng g-1-dw
      and 3.71 to 18.95 ng g-1-dw respectively. Out of all the tested OCPs, heptachlor,
      heptachlor epoxide, p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and beta
      hexachlorocyclohexane (beta-HCH) were the most abundant in the study area. The
      ratio of (beta-HCH/?HCHs) indicated that HCHs were originally from earlier usage
      of HCH in the area whereas the ratio of (p,p'-DDT/p,p'-DDE) showed that the
      majority of DDT components were recently introduced into most of the sampling
      locations. Even though there were relatively low concentrations of PBDEs and PCBs
      across the sampling sites, substantial amounts of PCBs were observed in Addis
      Ababa City. According to the established ecological risk indices, p,p'-DDT and
      gamma-HCH are the major concerns for potential adverse ecological impacts. This
      study provided the first comprehensive information on organohalogenated
      compounds' (OCs') occurrences, spatial distributions, and ecological risks in
      sediments of the Awash River Basin. Thus, the report will be very useful
      background information for further studies on sediment contamination with OCs' in
      the region. It also adds important first-hand data to the field of fresh water
      ecology and provides useful empirical evidence for setting pollution control
      priorities for an ecologically important, yet largely understudied region.

PMID- 30286180
TI  - LC3B is not recruited along with the autophagy elongation complex (ATG5-12/16L1)
      at HCV replication site and is dispensable for viral replication.
AB  - Hepatitis C virus (HCV) infection is known to induce autophagosome accumulation
      as observed by the typical punctate cytoplasmic distribution of LC3B-II in
      infected cells. Previously, we showed that viral RNA-dependent RNA polymerase
      (NS5B) interacts with ATG5, a major component of the autophagy elongation complex
      that is involved in the formation of double-membrane vesicles (DMV), and
      demonstrated that the autophagy elongation complex (ATG5-12/16L1) but not LC3B is
      required for proper membranous web formation. In this study, the colocalization
      and in situ interaction of all HCV replicase components with the constituent of
      the autophagy elongation complex and LC3B were analyzed. The results clearly show
      the recruitment of the elongation complex to the site of viral replication. Using
      in situ proximity ligation assay, we show that ATG5, but not ATG16L1, interacts
      with several HCV replicase components suggesting that the recruitment is directed
      via the ATG5-12 conjugate. Interestingly, no E3-like conjugation activity of ATG5
      12/16L1 can be detected at the at HCV replication site since LC3B-II is not found
      along with the elongation complex at the site of viral replication. In agreement
      with this result, no sign of in situ interaction of LC3B with the replicase
      components is observed. Finally, using dominant negative forms of ATG proteins,
      we demonstrate that ATG5-12 conjugate, but not LC3-II formation, is critical for
      viral replication. Altogether, these findings suggest that although HCV needs the
      elongation complex for its replication, it has developed a mechanism to avoid
      canonical LC3-II accumulation at viral replication site.

PMID- 30286183
TI  - Desmoplakin interacts with the coil 1 of different types of intermediate filament
      proteins and displays high affinity for assembled intermediate filaments.
AB  - The interaction of intermediate filaments (IFs) with the cell-cell adhesion
      complexes desmosomes is crucial for cytoskeletal organization and cell resilience
      in the epidermis and heart. The intracellular desmosomal protein desmoplakin
      anchors IFs to the cell adhesion complexes predominantly via its four last
      carboxy-terminal domains (C-terminus). However, it remains unclear why the C
      terminus of desmoplakin interacts with different IF types or if there are
      different binding affinities for each type of IFs that may influence the
      stability of cell-specific adhesion complexes. By yeast three-hybrid and
      fluorescence binding assays, we found that the coiled-coil 1 of the conserved
      central rod domain of the heterodimeric cytokeratins (Ks) 5 and 14 (K5/K14) was
      required for their interaction with the C-terminus of desmoplakin, while their
      unique amino head- and C-tail domains were dispensable. Similar findings were
      obtained in vitro with K1/K10, and the type III IF proteins desmin and vimentin.
      Binding assays testing the C-terminus of desmoplakin with assembled K5/K14 and
      desmin IFs yielded an apparent affinity in the nM range. Our findings reveal that
      the same conserved domain of IF proteins binds to the C-terminus of desmoplakin,
      which may help explain the previously reported broad binding IF-specificity to
      desmoplakin. Our data suggest that desmoplakin high-affinity binding to diverse
      IF proteins ensures robust linkages of IF cytoskeleton and desmosomes that
      maintain the structural integrity of cellular adhesion complexes. In summary, our
      results give new insights into the molecular basis of the IF-desmosome
      association.

PMID- 30286182
TI  - Circular RNA and mRNA profiling reveal competing endogenous RNA networks during
      avian leukosis virus, subgroup J-induced tumorigenesis in chickens.
AB  - Avian leukosis virus subgroup J (ALV-J) can induce myeloid tumors and hemangiomas
      in chickens and causes severe economic losses with commercial layer chickens and
      meat-type chickens. Here, we generated ribominus RNA sequencing data from three
      normal chicken spleen tissues and three ALV-J-infected chicken spleen tissues.
      Structure analysis of transcripts showed that, compared to mRNAs and lncRNAs,
      chicken circRNAs shared relatively shorter transcripts and similar GC content.
      Differentially expression analysis showed 152 differentially expressed circRNAs
      with 106 circRNAs up regulated and 46 circRNAs down regulated. Through comparing
      differentially expressed circRNA host genes and mRNAs and performed ceRNA network
      analysis, we found several tumor or immune-related genes, in which, there were
      four genes existed in both differentially expressed mRNAs and circRNA host genes
      (Dock4, Fmr1, Zfhx3, Ralb) and two genes (Mll, Aoc3) involved in ceRNA network.
      We further characterized one exon-intron circRNA derived from HRH4 gene in the
      ceRNA network, termed circHRH4, which is an abundant and stable circRNA expressed
      in various tissues and cells in chicken and localizes in cytoplasm. Our results
      provide new insight into the pathology of ALV-J infection and circRNAs may also
      mediate tumorigenesis in chicken.

PMID- 30286184
TI  - Lung tumor segmentation methods: Impact on the uncertainty of radiomics features
      for non-small cell lung cancer.
AB  - PURPOSE: To evaluate the uncertainty of radiomics features from contrast-enhanced
      breath-hold helical CT scans of non-small cell lung cancer for both manual and
      semi-automatic segmentation due to intra-observer, inter-observer, and inter
      software reliability. METHODS: Three radiation oncologists manually delineated
      lung tumors twice from 10 CT scans using two software tools (3D-Slicer and MIM
      Maestro). Additionally, three observers without formal clinical training were
      instructed to use two semi-automatic segmentation tools, Lesion Sizing Toolkit
      (LSTK) and GrowCut, to delineate the same tumor volumes. The accuracy of the semi
      automatic contours was assessed by comparison with physician manual contours
      using Dice similarity coefficients and Hausdorff distances. Eighty-three
      radiomics features were calculated for each delineated tumor contour. Informative
      features were identified based on their dynamic range and correlation to other
      features. Feature reliability was then evaluated using intra-class correlation
      coefficients (ICC). Feature range was used to evaluate the uncertainty of the
      segmentation methods. RESULTS: From the initial set of 83 features, 40 radiomics
      features were found to be informative, and these 40 features were used in the
      subsequent analyses. For both intra-observer and inter-observer reliability, LSTK
      had higher reliability than GrowCut and the two manual segmentation tools. All
      observers achieved consistently high ICC values when using LSTK, but the ICC
      value varied greatly for each observer when using GrowCut and the manual
      segmentation tools. For inter-software reliability, features were not
      reproducible across the software tools for either manual or semi-automatic
      segmentation methods. Additionally, no feature category was found to be more
      reproducible than another feature category. Feature ranges of LSTK contours were
      smaller than those of manual contours for all features. CONCLUSION: Radiomics
      features extracted from LSTK contours were highly reliable across and among
      observers. With semi-automatic segmentation tools, observers without formal
      clinical training were comparable to physicians in evaluating tumor segmentation.

PMID- 30286181
TI  - Conotoxin MVIIA improves cell viability and antioxidant system after spinal cord
      injury in rats.
AB  - This study evaluates whether intrathecal MVIIA injection after spinal cord injury
      (SCI) elicits neuroprotective effects. The test rats were randomly distributed
      into six groups- sham, placebo, MVIIA 2.5 MUM, MVIIA 5 MUM, MVIIA 10 MUM, and
      MVIIA 20 MUM-and were administered the treatment four hours after SCI. After the
      optimal MVIIA dose (MVIIA 10 MUM) was defined, the best time for application, one
      or four hours, was analyzed. Locomotor hind limb function and side effects were
      assessed. Forty-eight hours after the injury and immediately after euthanasia,
      spinal cord segments were removed from the test rats. Cell viability, reactive
      oxygen species, lipid peroxidation, and glutamate release were investigated. To
      examine the MVIIA mechanism of action, the gene expressions of pro-apoptotic
      (Bax, nNOS, and caspase-3, -8, -9, -12) and anti-apoptotic (Bcl-xl) factors in
      the spinal cord tissue samples were determined by real-time PCR, and the
      activities of antioxidant enzymes were also investigated. Application of
      intrathecal MVIIA 10 MUM four hours after SCI prompted a neuroprotective effect:
      neuronal death decreased (22.46%), oxidative stress diminished, pro-apoptotic
      factors (Bax, nNOS, and caspase-3, -8) were expressed to a lesser extent, and
      mitochondrial viability as well as anti-apoptotic factor (Bcl-xl) expression
      increased. These results suggested that MVIIA provided neuroprotection through
      antioxidant effects. Indeed, superoxide dismutase (188.41%), and glutathione
      peroxidase (199.96%), reductase (193.86%), and transferase (175.93%) expressions
      increased. Therefore, intrathecal MVIIA (MVIIA 10 MUM, 4 h) application has
      neuroprotective potential, and the possible mechanisms are related to antioxidant
      agent modulation and to intrinsic and extrinsic apoptotic pathways.

PMID- 30286186
TI  - Why is the environment important for decision making? Local reservoir model for
      choice-based learning.
AB  - Decision making based on behavioral and neural observations of living systems has
      been extensively studied in brain science, psychology, neuroeconomics, and other
      disciplines. Decision-making mechanisms have also been experimentally implemented
      in physical processes, such as single photons and chaotic lasers. The findings of
      these experiments suggest that there is a certain common basis in describing
      decision making, regardless of its physical realizations. In this study, we
      propose a local reservoir model to account for choice-based learning (CBL). CBL
      describes decision consistency as a phenomenon where making a certain decision
      increases the possibility of making that same decision again later. This
      phenomenon has been intensively investigated in neuroscience, psychology, and
      other related fields. Our proposed model is inspired by the viewpoint that a
      decision is affected by its local environment, which is referred to as a local
      reservoir. If the size of the local reservoir is large enough, consecutive
      decision making will not be affected by previous decisions, thus showing lower
      degrees of decision consistency in CBL. In contrast, if the size of the local
      reservoir decreases, a biased distribution occurs within it, which leads to
      higher degrees of decision consistency in CBL. In this study, an analytical
      approach for characterizing local reservoirs is presented, as well as several
      numerical demonstrations. Furthermore, a physical architecture for CBL based on
      single photons is discussed, and the effects of local reservoirs are numerically
      demonstrated. Decision consistency in human decision-making tasks and in
      recruiting empirical data is evaluated based on the local reservoir. This
      foundation based on a local reservoir offers further insights into the
      understanding and design of decision making.

PMID- 30286188
TI  - Inoculating science against potential pandemics and information hazards.
AB  - The recent de novo assembly of horsepox is an instructive example of an
      information hazard: published methods enabling poxvirus synthesis led to media
      coverage spelling out the implications, efficiently disseminating true
      information that might be used to cause harm. Whether or not the benefits
      justified the risks, the horsepox saga provides ample reason to upgrade the
      current system for screening synthesized DNA for hazardous sequences, which does
      not cover the majority of firms and cannot reliably prevent the assembly of
      potentially pandemic pathogens. An upgraded system might leverage one-way
      encryption to confidentially scrutinize virtually all commercial production by a
      cooperative international network of servers whose integrity can be verified by
      third parties. Funders could support participating institutions to ease the
      transition or outright subsidize the market to make clean DNA cheaper, while
      boycotts by journals, institutions, and funders could ensure compliance and
      require hardware-level locks on future DNA synthesizers. However, the underlying
      problem is that security and safety discussions among experts typically follow
      potentially hazardous events rather than anticipating them. Changing norms and
      incentives to favor preregistration and advisory peer review of planned
      experiments could test alternatives to the current closeted research model in
      select areas of science. Because the fields of synthetic mammalian virology and
      especially gene drive research involve technologies that could be unilaterally
      deployed and may self-replicate in the wild, they are compelling candidates for
      initial trials of early-stage peer review.

PMID- 30286185
TI  - Features of urinary Escherichia coli isolated from children with complicated and
      uncomplicated urinary tract infections in Mexico.
AB  - The Hospital Infantil de Mexico Federico Gomez (HIMFG) is a tertiary care
      hospital in Mexico City where Escherichia coli is frequently isolated from the
      urine samples of pediatric patients with urinary tract infections. A collection
      of 178 urinary Escherichia coli (UEc) isolates associated with complicated and
      uncomplicated urinary tract infections were evaluated in this study. The patterns
      of resistance to 9 antibiotic classes showed that 60.7% of the UEc isolates had a
      highly multidrug-resistant (MDR) profile. Genetic diversity analyses of the UEc
      isolates showed a high variability and revealed 16 clusters associated with four
      phylogenetic groups, namely, groups A, B1, B2, and D. Phylogenetic group B2 was
      widely associated with the 16 clusters as well as with virulence and fitness
      genes. The virulence and fitness genes in the UEc isolates, which included
      fimbriae-, siderophore-, toxin-, and mobility-associated genes, were grouped as
      occurring at a low, variable, or high frequency. Interestingly, only the papF
      gene could be amplified from some UEc isolates, and the sequence analysis of the
      pap operon identified an insertion sequence (IS) element and gene loss. These
      data suggested pathoadaptability and the development of immune system evasion,
      which was confirmed by the loss of P fimbriae-associated agglutination in the UEc
      isolates. E. coli clone O25-ST131 had a prevalence of 20.2% among the UEc
      isolates; these isolates displayed both a highly MDR profile and the presence of
      the papGII, fimH, papGIII, iutD, sat, hlyA, and motA genes. In conclusion, the
      UEc isolates from complicated urinary tract infection (cUTI) were characterized
      as being MDR, highly genetically diverse, and associated with phylogenetic group
      B2 and many virulence and fitness genes. Additionally, gene loss and IS elements
      were identified in some UEc isolates identified as clone O25-ST131.

PMID- 30286189
TI  - Toward the "unravelling" of HIV: Host cell factors involved in HIV-1 core
      uncoating.

PMID- 30286187
TI  - Comparison of the IPSA and HIPO algorithms for interstitial tongue high-dose-rate
      brachytherapy.
AB  - PURPOSE: This study aimed to compare the inverse planning simulated annealing
      (IPSA) stochastic algorithm with the hybrid inverse planning and optimization
      (HIPO) algorithm for interstitial tongue high-dose-rate (HDR) brachytherapy.
      METHODS: Twenty patients who received radiotherapy for tongue cancer using
      interstitial HDR brachytherapy were retrospectively selected for this study.
      Oncentra Brachy v. 4.3 was used for IPSA and HIPO planning. Four to eight fixed
      catheter configurations were determined according to the target shape. During the
      optimization process, predetermined constrain values were used for each IPSA and
      HIPO plan. The dosimetric parameters and dwell time were analyzed to evaluate the
      performances of the plans. RESULTS: The total dwell time using IPSA was 4 seconds
      longer than that of HIPO. The number of active positions per catheter for the
      IPSA plans were approximately 2.5 fewer than those of the HIPO plans. The dose
      volumetric parameters related to the clinical target volume with IPSA were lower
      than those with HIPO. In terms of the dose-volumetric parameters related to
      normal tissue, HIPO tended to associate with slightly higher values than IPSA,
      without statistical significance. After GrO, the target coverages were satisfied
      to clinical goal for all patients. The total dwell times was approximately
      increased by 10%. CONCLUSIONS: The IPSA and HIPO dose optimization algorithms
      generate similar dosimetric results. In terms of the dwell time, HIPO appears to
      be more beneficial.

PMID- 30286190
TI  - Synthetic horsepox viruses and the continuing debate about dual use research.

PMID- 30286191
TI  - A control mechanism for intra-mural peri-arterial drainage via astrocytes: How
      neuronal activity could improve waste clearance from the brain.
AB  - The mechanisms behind the clearance of soluble waste from deep within the
      parenchyma of the brain remain unclear. Experimental evidence reveals that one
      pathway for clearance of waste, termed intra-mural peri-arterial drainage (IPAD),
      is the rapid drainage of interstitial fluid along basement membranes (BM) of the
      smooth muscle cells of cerebral arteries; failure of IPAD is closely associated
      with the pathology of Alzheimer's disease (AD), but its driving mechanism remains
      unclear. We have previously shown that arterial pulsations generated by the heart
      beat are not strong enough to drive IPAD. Here we present computational evidence
      for a mechanism for clearance of waste from the brain that is driven by
      functional hyperaemia, that is, the dilatation of cerebral arterioles as a
      consequence of increased nutrient demand from neurons. This mechanism is based on
      our model for the flow of fluid through the vascular BM. It accounts for
      clearance rates observed in mouse experiments, and aligns with pathological
      observations and recommendations to lower the individual risk of AD, such as
      mental and physical activity. Thus, our neurovascular hypothesis should act as
      the new working hypothesis for the driving force behind IPAD.

PMID- 30286192
TI  - Association between mitral valve prolapse and sudden sensorineural hearing loss:
      A case-control population-based study.
AB  - This study aimed to evaluate the relationship between sudden sensorineural
      hearing loss (SSNHL) and MVP using a population-based dataset. Data for this case
      control study were retrieved from the Taiwan Longitudinal Health Insurance
      Database. In total, 3399 cases of newly diagnosed SSNHL were identified. We used
      propensity score matching to select 3399 comparison patients (one for every case)
      from the same dataset. The selected matching variables included age, sex, monthly
      income, geographical location, urbanization level of the patient's residence,
      hypertension, diabetes, and hyperlipidemia. Chi-squared tests were used to
      compare differences in sociodemographic characteristics, while conditional
      logistic regression analyses were used to examine the association of SSNHL with
      previously diagnosed MVP. Of the 6798 sampled subjects, 131 (1.93%) patients had
      received a diagnosis of MVP prior to the index date. A significant difference in
      the prevalence of prior MVP between cases and controls (2.41% vs. 1.44%, p =
      0.004) was observed. The conditional logistic regression analysis conditioned on
      gender, age, monthly income, urbanization level, geographic region,
      hyperlipidemia, diabetes, and hypertension suggested that the odds ratio of prior
      MVP for cases was 1.69 (95% confidence interval (CI): 1.18~2.42) compared to
      controls. Our study found that patients with MVP had a 1.69-fold higher risk of
      getting SSNHL compared to patients without MVP.

PMID- 30286193
TI  - Correction: Stochastic Mesocortical Dynamics and Robustness of Working Memory
      during Delay-Period.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0144378.].

PMID- 30286194
TI  - Correction: A knowledge, attitude, and practice survey on mediation among
      clinicians in a tertiary-care hospital in Singapore.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0199885.].

PMID- 30286196
TI  - Correction: Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein
      levels predict the presence of fibrotic nonalcoholic steatohepatitis (NASH) and
      NASH cirrhosis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0202226.].

PMID- 30286195
TI  - Tropheryma whipplei colonization in HIV-infected individuals is not associated
      with lung function or inflammation.
AB  - Studies demonstrate that Tropheryma whipplei (T. whipplei) is present in the
      lungs of healthy individuals without acute respiratory symptoms or acute
      respiratory infection and is more common in the lungs of HIV-infected individuals
      and in smokers. The impact of T. whipplei colonization in the lung on local
      inflammation and pulmonary dysfunction in HIV-infected individuals is currently
      unknown. In this study, we performed specific polymerase chain reaction (PCR) and
      sequencing for T. whipplei in bronchoalveolar lavage (BAL) and induced sputum
      (IS) samples in 76 HIV-infected participants from three clinical sites. Pulmonary
      function and proinflammatory cytokine and chemokine levels in BAL were measured.
      Frequency of T. whipplei in either BAL or IS was 43.4%. The sensitivity and
      specificity of IS compared to BAL for detection of T. whipplei was 92.3% and
      84.2%, respectively, and isolates of T. whipplei in the BAL and IS in the same
      subject shared genetic identity. Pulmonary function measures were not associated
      with T. whipplei colonization, and proinflammatory cytokine and chemokine levels
      in BAL and plasma as well as percentages of inflammatory cells in BAL and IS were
      not higher in colonized individuals. Overall, these results indicate that T.
      whipplei colonization in the lung is common, but may not be associated with
      decreased pulmonary function or inflammation in HIV-infected individuals.

PMID- 30286197
TI  - Horsepox: Framing a dual use research of concern debate.

PMID- 30286199
TI  - Correction: Optimization of the standard genetic code according to three codon
      positions using an evolutionary algorithm.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0201715.].

PMID- 30286198
TI  - Participation of the spleen in the IgA immune response in the gut.
AB  - The role of the spleen in the induction of an immune response to orally
      administered antigens is still under discussion. Although it is well known that
      after oral antigen administration specific germinal centres are not only formed
      in the Peyers patches (PP) and the mesenteric lymph nodes (mLN) but also in the
      spleen, there is still a lack of functional data showing a direct involvement of
      splenic B cells in an IgA immune response in the gut. In addition, after removal
      of mLN a high level of IgA+ B cells was observed in the gut. Therefore, in this
      study we analysed the role of the spleen in the induction of IgA+ B cells in the
      gut after mice were orally challenged with antigens. Here we have shown that
      antigen specific splenic IgM+ B cells after in vitro antigen stimulation as well
      as oral immunisation of donor mice were able to migrate into the gut of recipient
      mice, where they predominantly switch to IgA+ plasma cells. Furthermore,
      stimulation of recipient mice by orally administered antigens enhanced the
      migration of the splenic B cells into the gut as well as their switch to IgA+
      plasma cells. Removal of the mLN led to a higher activation level of the splenic
      B cells. Altogether, our results imply that splenic IgM+ B cells migrate in the
      intestinal lamina propria, where they differentiate into IgA+ plasma cells and
      subsequently proliferate. In conclusion, we demonstrated that the spleen plays a
      major role in the gut immune response serving as a reservoir of immune cells that
      migrate to the site of antigen entrance.

PMID- 30286200
TI  - Sport motivation and doping in adolescent athletes.
AB  - BACKGROUND: Although performance-enhancing drugs appear to be prevalent in
      adolescent sports, relatively little attention has been paid to why adolescent
      athletes decide to use these drugs. In this study, we examine doping among
      adolescents from a motivational perspective and explore how motivational
      variables, such as achievement goal orientations and the perceived self
      determination of sports activities, may be related to moral attitudes, doping
      intentions and doping behavior in adolescents who participate in competitive
      sports. METHODOLOGY: The study included 1035 adolescents participating in
      competitive sports from all regions of the Czech Republic (mean age = 16.3
      years). The respondents completed a battery of questionnaires assessing their
      achievement goal orientations (task, ego), sports motivation at various levels of
      self-determination (intrinsic motivation, external regulation, amotivation),
      moral attitudes toward sport competition (acceptance of cheating, keeping winning
      in proportion, attitudes toward doping), doping intentions and doping behavior. A
      structural equation model was used to test the relations among motivational
      variables, attitudes, intentions and doping behavior. PRINCIPAL RESULTS: Our
      analyses indicated a good fit with the proposed model, which explained 59% of the
      variance in doping intentions and 17.6% of the variance in doping behavior.
      Within the model, task orientation was positively associated with intrinsic
      motivation and lower amotivation, whereas ego orientation was positively
      associated with extrinsic regulation and amotivation. Furthermore, intrinsic
      motivation was positively associated with keeping winning in proportion and
      negatively associated with acceptance of cheating and attitudes toward doping;
      the less self-determined forms of motivation showed opposite relationships.
      However, only the acceptance of cheating and attitudes toward doping were related
      to doping intention, which subsequently predicted doping behavior.
      CONCLUSIONS/SIGNIFICANCE: The results provide further evidence that sports
      motivation represents a psychological variable that should be considered in anti
      doping policies, programs, and interventions aimed at the adolescent population
      because motivation was linked to the doping-related attitudinal variables and
      also partially mediated the effect of achievement goal orientations in this
      regard. On the basis of these results, we may argue that the focus on intrinsic
      enjoyment, self-referenced criteria of success and self-improvement may be
      related to more negative attitudes toward doping and cheating, lower doping
      intentions and less frequent doping behavior, whereas the emphasis on
      competition, comparison with others and external motivation appear to be related
      to the opposite outcomes.

PMID- 30286201
TI  - B cell responses to apoptotic cells in MFG-E8-/- mice.
AB  - Defective clearance of apoptotic cells in MFG-E8 deficient mice results in lupus
      like disease in the mixed B6x129, but not pure B6 background. The lack of overt
      autoimmunity in MFG-E8-/- B6 mice suggests that accumulation of apoptotic cells
      is not sufficient to break central tolerance. However, the delayed clearance of
      apoptotic cells in the follicles of MFG-E8-/- B6 mice provides an excellent
      opportunity to investigate how B cells respond to excessive apoptotic cells in
      the periphery under relatively non-inflammatory conditions. In MFG-E8-/- B6 mice,
      we found increased IgG2c production against apoptotic cells and oxidized LDL.
      Apoptotic cell induced antibody responses depended on MyD88 signal and T cell
      help. In addition, MFG-E8-/- B6 mice had enlarged MZ B cell compartments as well
      as an enhanced antibody response to NP-Ficoll. Moreover, a significant percentage
      of MZ B cells in aged MFG-E8-/- B6 mice migrated into follicles. Injecting
      apoptotic cells or oxidized LDL into wild type mice as well as physiological
      accumulation of LDL in ApoE-/- mice recapitulated the translocation of MZ B
      cells. To determine how MFG-E8 deficiency affects the functions of autoreactive B
      cells specific for nucleic acids in the periphery under non-inflammatory
      conditions, we utilized BCR transgenic mice to bypass central selection and
      compared the differentiation of TLR9 dependent anti-dsDNA 56R B cells and TLR7
      dependent anti-ssRNA H564 B cells in MFG-E8-/- mice. In MFG-E8-/- 56R mice, anti
      dsDNA specific 56R/Vkappa38c B cells differentiated into MZ B cells but not AFCs.
      On the contrary, in MFG-E8-/-H564 mice, anti-ssRNA specific H564 B cells further
      differentiated into GC B cells and AFCs. Adoptive transfer of activated
      autoreactive B cells confirmed that H564 B cells were more sensitive to apoptotic
      cell antigens than 56R B cells. Our observations provide new insights about the
      MZ B cell translocation in lupus patients as well as the dichotomy of TLR9 and
      TLR7 signals in the pathogenesis of lupus.

PMID- 30286202
TI  - Correction: Can excreted thiocyanate be used to detect cyanide exposure in live
      reef fish?
AB  - [This corrects the article DOI: 10.1371/journal.pone.0196841.].

PMID- 30286203
TI  - Scavenger receptor-C acts as a receptor for Bacillus thuringiensis vegetative
      insecticidal protein Vip3Aa and mediates the internalization of Vip3Aa via
      endocytosis.
AB  - The vegetative insecticidal proteins (Vip), secreted by many Bacillus
      thuringiensis strains during their vegetative growth stage, are genetically
      distinct from known insecticidal crystal proteins (ICPs) and represent the second
      generation insecticidal toxins. Compared with ICPs, the insecticidal mechanisms
      of Vip toxins are poorly understood. In particular, there has been no report of a
      definite receptor of Vip toxins to date. In the present study, we identified the
      scavenger receptor class C like protein (Sf-SR-C) from the Spodoptera frugiperda
      (Sf9) cells membrane proteins that bind to the biotin labeled Vip3Aa, via the
      affinity magnetic bead method coupled with HPLC-MS/MS. We then certified Vip3Aa
      protoxin could interact with Sf-SR-C in vitro and ex vivo. In addition,
      downregulation of SR-C expression in Sf9 cells and Spodoptera exigua larvae
      midgut reduced the toxicity of Vip3Aa to them. Coincidently, heterologous
      expression of Sf-SR-C in transgenic Drosophila midgut significantly enhanced the
      virulence of Vip3Aa to the Drosophila larvae. Moreover, the complement control
      protein domain and MAM domain of Sf-SR-C are involved in the interaction with
      Vip3Aa protoxin. Furthermore, endocytosis of Vip3Aa mediated by Sf-SR-C
      correlates with its insecticidal activity. Our results confirmed for the first
      time that Sf-SR-C acts as a receptor for Vip3Aa protoxin and provides an insight
      into the mode of action of Vip3Aa that will significantly facilitate the study of
      its insecticidal mechanism and application.

PMID- 30286204
TI  - Psychometric properties of the German version of the Leicester Cough
      Questionnaire in sarcoidosis.
AB  - BACKGROUND: Cough is one of the most common symptoms in general and pulmonary
      medicine with profound negative impact on health-related quality of life (HRQL).
      The Leicester Cough Questionnaire (LCQ) is a validated HRQL questionnaire, yet a
      validated German version of the LCQ is not available and it has never been tested
      in a cohort with sarcoidosis. OBJECTIVES: To translate the LCQ into German and
      determine its psychometric properties. METHODS: The LCQ was translated in a
      forward-backward approach. Structured interviews in sarcoidosis patients were
      performed. Subsequently, sarcoidosis patients were asked to answer the German LCQ
      and comparative questionnaires. Distribution properties, item difficulty,
      concurrent validity, Rasch model fit and internal consistency of the German LCQ
      were determined. RESULTS: 200 patients with sarcoidosis were included. We provide
      evidence for reliability, unidimensionality and internal consistency. However,
      only a moderate correlation with general and respiratory-specific HRQL
      questionnaires, no Rasch model fit could be shown. Skewed responses caused by
      floor effects were detected. CONCLUSION: We demonstrate that the German LCQ is
      valid and reliable and its psychometric properties fulfil the standards required
      for its use in clinical settings as well as in interventional trials.

PMID- 30286206
TI  - Correction: Development of a novel immunoproteasome digestion assay for synthetic
      long peptide vaccine design.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0199249.].

PMID- 30286205
TI  - Hepatitis C virus genetic diversity by geographic region within genotype 1-6
      subtypes among patients treated with glecaprevir and pibrentasvir.
AB  - Hepatitis C virus (HCV) is genetically diverse and includes 7 genotypes and 67
      confirmed subtypes, and the global distribution of each HCV genotype (GT) varies
      by geographic region. In this report, we utilized a large dataset of NS3/4A and
      NS5A sequences isolated from 2348 HCV GT1-6-infected patients treated with the
      regimen containing glecaprevir/pibrentasvir (GLE/PIB) to assess genetic diversity
      within HCV subtypes by geographic region using phylogenetic analyses, and
      evaluated the prevalence of baseline amino acid polymorphisms in NS3 and NS5A by
      region/country and phylogenetic cluster. Among 2348 NS3/4A and NS5A sequences,
      phylogenetic analysis identified 6 genotypes and 44 subtypes, including 3 GT1, 8
      GT2, 3 GT3, 13 GT4, 1 GT5, and 16 GT6 subtypes. Phylogenetic analysis of HCV
      subtype 1a confirmed the presence of two clades, which differed by geographic
      region distribution and NS3 Q80K prevalence. We detected phylogenetic clustering
      by country in HCV subtypes 1a, 1b, 2a, 2b, and 5a, suggesting that genetically
      distinct virus lineages are circulating in different countries. In addition, two
      clades were detected in HCV GT4a and GT6e, and NS5A amino acid polymorphisms were
      differentially distributed between the 2 clades in each subtype. The prevalence
      of NS3 and NS5A baseline polymorphisms varied substantially by genotype and
      subtype; therefore, we also determined the activity of GLE or PIB against
      replicons containing NS3/4A or NS5A from HCV GT1-6 clinical samples representing
      6 genotypes and 21 subtypes overall. GLE and PIB retained activity against the
      majority of HCV replicons containing NS3/4A or NS5A from HCV GT1-6 clinical
      samples, with a median EC50 of 0.29 nM for GLE and 1.1 pM for PIB in a transient
      replicon assay. The data presented in this report expands the available data on
      HCV epidemiology, subtype diversity by geographic region, and NS3 and NS5A
      baseline polymorphism prevalence.

PMID- 30286207
TI  - A rare case of visceral leishmaniasis in an immunocompetent traveler returning to
      the United States from Europe.
AB  - A young, healthy traveler returning to the United States presented with fever,
      night sweats, splenomegaly, and pancytopenia. Bone marrow biopsy revealed
      leishmaniasis (Leishmania infantum), likely acquired in southern France. Although
      many cases of endemic visceral leishmaniasis (VL) have been reported in Europe,
      this is a rare case of imported VL in a healthy traveler returning from Europe to
      the US. Despite successful initial treatment with liposomal amphotericin B
      (LamB), relapse occurred. Treatments for VL in immunocompetent individuals are
      highly effective, but relapse can occur. There is more extensive experience in
      endemic areas with treating relapse that may be lacking in North America. This
      case alerts physicians in the US that immunocompetent adults can acquire VL
      during brief visits to endemic areas in Europe. It is important that travelers be
      counseled on preventive measures. Patients should be monitored after treatment
      for relapse.

PMID- 30286208
TI  - Can we predict when to start renal replacement therapy in patients with chronic
      kidney disease using 6 months of clinical data?
AB  - PURPOSE: We aimed to develop a model of chronic kidney disease (CKD) progression
      for predicting the probability and time to progression from various CKD stages to
      renal replacement therapy (RRT), using 6 months of clinical data variables
      routinely measured at healthcare centers. METHODS: Data were derived from the
      electronic medical records of Ajou University Hospital, Suwon, South Korea from
      October 1997 to September 2012. We included patients who were diagnosed with CKD
      (estimated glomerular filtration rate [eGFR] < 60 mL.min-1.1.73 m-2 for >= 3
      months) and followed up for at least 6 months. The study population was randomly
      divided into training and test sets. RESULTS: We identified 4,509 patients who
      met reasonable diagnostic criteria. Patients were randomly divided into 2 groups,
      and after excluding patients with missing data, the training and test sets
      included 1,625 and 1,618 patients, respectively. The integral mean was the most
      powerful explanatory (R2 = 0.404) variable among the 8 modified values. Ten
      variables (age, sex, diabetes mellitus[DM], polycystic kidney disease[PKD], serum
      albumin, serum hemoglobin, serum phosphorus, serum potassium, eGFR (calculated by
      Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]), and urinary
      protein) were included in the final risk prediction model for CKD stage 3 (R2 =
      0.330). Ten variables (age, sex, DM, GN, PKD, serum hemoglobin, serum blood urea
      nitrogen[BUN], serum calcium, eGFR(calculated by Modification of Diet in Renal
      Disease[MDRD]), and urinary protein) were included in the final risk prediction
      model for CKD stage 4 (R2 = 0.386). Four variables (serum hemoglobin, serum BUN,
      eGFR(calculated by MDRD) and urinary protein) were included in the final risk
      prediction model for CKD stage 5 (R2 = 0.321). CONCLUSION: We created a
      prediction model according to CKD stages by using integral means. Based on the
      results of the Brier score (BS) and Harrel's C statistics, we consider that our
      model has significant explanatory power to predict the probability and interval
      time to the initiation of RRT.

PMID- 30286209
TI  - Serology, virulence and molecular characteristics of Vibrio parahaemolyticus
      isolated from seafood in Zhejiang province.
AB  - Vibrio parahaemolyticus is a leading foodborne pathogen in southeastern China. In
      this study, 105 strains of V. parahaemolyticus were isolated from fresh seafood
      in 2013 and 2014. The serotypes, virulence-associated genes and sequence types
      (STs) of these strains were analyzed. 26 defined serotypes were identified and 69
      strains (65.7%) had untypeable O or K antigen. 8 strains (7.6%) had the virulence
      associated gene tdh and no strain carried the trh gene. 45.7% (48/105) of
      isolates contained all four T3SS1 genes and 50% (4/8) tdh+ trh- V.
      parahaemolyticus isolates lacked at least one of the four tested T3SS2alpha
      genes. 105 strains could be categorized into 84 STs and only 3 STs (ST3, ST8,
      ST675) had appeared in clinical strains. V. parahaemolyticus strains from seafood
      have more diverse and untypeable serotypes, less virulence-associated genes and
      more STs than strains from clinical sources.

PMID- 30286210
TI  - Epigallocatechin-3 gallate prevents pressure overload-induced heart failure by up
      regulating SERCA2a via histone acetylation modification in mice.
AB  - Heart failure is a common, costly, and potentially fatal condition. The cardiac
      sarcoplasmic reticulum Ca-ATPase (SERCA2a) plays a critical role in the
      regulation of cardiac function. Previously, low SERCA2a expression was revealed
      in mice with heart failure. Epigallocatechin-3-gallate (EGCG) can function as an
      epigenetic regulator and has been reported to enhance cardiac function. However,
      the underlying epigenetic regulatory mechanism is still unclear. In this study,
      we investigated whether EGCG can up-regulate SERCA2a via histone acetylation and
      play role in preventing heart failure. For this, we generated a mouse model of
      heart failure by performing a minimally invasive transverse aortic constriction
      (TAC) operation and used this to test the effects of EGCG. The TAC+EGCG group
      showed nearly normal cardiac function compared to that in the SHAM group. The
      expression of SERCA2a was decreased at both the mRNA and protein levels in the
      TAC group but was enhanced in the TAC+EGCG group. Levels of AcH3 and AcH3K9 were
      determined to decrease near the promoter region of Atp2a2 (the gene encoding
      SERCA-2a) in the TAC group, but were elevated in the TAC+EGCG group. Meanwhile,
      HDAC1 activity and binding near the Atp2a2 promoter were increased in the TAC
      group but decreased with EGCG addition. Further, binding levels of GATA4 and
      Mef2c near the Atp2a2 promoter region were reduced in TAC hearts, which might
      have been caused by histone hypoacetylation; this was reversed by EGCG. Together,
      upregulation of SERCA2a via the modification of histone acetylation plays a role
      in EGCG-mediated prevention of pressure overload-induced heart failure, and this
      might represent a novel pharmacological target for the treatment of heart
      failure.

PMID- 30175239
TI  - Mainstreaming as rhetoric or reality? Gender and global health at the World Bank.
AB  - Background: Over the past decade gender mainstreaming has gained visibility at
      global health organisations. The World Bank, one of the largest funders of global
      health activities, released two World Development Reports showcasing its gender
      policies, and recently announced a $1 billion initiative for women's
      entrepreneurship. We summarise the development of the Bank's gender policies and
      analyse its financing of gender projects in the health sector. This article is
      intended to provide background for future research on the Bank's gender and
      global health portfolio. Methods: First, we constructed a timeline of the Bank's
      gender policy development, through a review of published articles, grey
      literature, and Bank documents and reports. Second, we performed a health-focused
      analysis of publicly available Bank gender project databases, to track its
      financing of health sector projects with a gender 'theme' from 1985-2017.
      Results: The Bank's gender policy developed through four major phases from 1972
      2017: 'women in development' (WID), institutionalisation of WID, gender
      mainstreaming, and gender equality through 'smart economics'. In the more
      inclusive Bank project database, projects with a gender theme comprised between
      1.3% (1985-1989) and 6.2% (2010-2016) of all Bank commitments.  Most funding
      targeted middle-income countries and particular health themes, including
      communicable diseases and health systems. Major gender-related trust funds were
      absent from both databases. The Bank reports that 98% of its lending is 'gender
      informed', which indicates that the gender theme used in its publicly available
      project databases is poorly aligned with its criteria for gender informed
      projects. Conclusion: The Bank focused most of its health sector gender projects
      on women's and girls' issues. It is increasingly embracing private sector
      financing of its gender activities, which may impact its poverty alleviation
      agenda. Measuring the success of gender mainstreaming in global health will
      require the Bank to release more information about its gender indicators and
      projects.

PMID- 30286213
TI  - Validation of the Persian Language Version of the Standardized Cosmesis and
      Health Nasal Outcomes Survey (SCHNOS).

PMID- 30286214
TI  - Cognitive Impairment Among Older Patients With Hematologic Cancers.

PMID- 30286215
TI  - How Pharmacy Benefit Managers Add to Financial Toxicity: The Copay Accumulator
      Program.

PMID- 30286211
TI  - Microvesicles from malaria-infected red blood cells activate natural killer cells
      via MDA5 pathway.
AB  - Natural killer (NK) cells provide the first line of defense against malaria
      parasite infection. However, the molecular mechanisms through which NK cells are
      activated by parasites are largely unknown, so is the molecular basis underlying
      the variation in NK cell responses to malaria infection in the human population.
      Here, we compared transcriptional profiles of responding and non-responding NK
      cells following exposure to Plasmodium-infected red blood cells (iRBCs) and
      identified MDA5, a RIG-I-like receptor involved in sensing cytosolic RNAs, to be
      differentially expressed. Knockout of MDA5 in responding human NK cells by
      CRISPR/cas9 abolished NK cell activation, IFN-gamma secretion, lysis of iRBCs.
      Similarly, inhibition of TBK1/IKKepsilon, an effector molecule downstream of
      MDA5, also inhibited activation of responding NK cells. Conversely, activation of
      MDA5 by liposome-packaged poly I:C restored non-responding NK cells to lyse
      iRBCs. We further show that microvesicles containing large parasite RNAs from
      iRBCs activated NK cells by fusing with NK cells. These findings suggest that NK
      cells are activated through the MDA5 pathway by parasite RNAs that are delivered
      to the cytoplasm of NK cells by microvesicles from iRBCs. The difference in MDA5
      expression between responding and non-responding NK cells following exposure to
      iRBCs likely contributes to the variation in NK cell responses to malaria
      infection in the human population.

PMID- 30286216
TI  - Aspirin and Chemoprevention-Have We Arrived?

PMID- 30286217
TI  - National Trends in Ocular Injury: Differing Studies, Common Call to Action.

PMID- 30286218
TI  - The 2018 American Head and Neck Society Presidential Address-Reflections.
AB  - Jonathan C. Irish, President of the American Head and Neck Society (AHNS) for
      2017 to 2018, in his Presidential Address highlights the challenges and
      opportunities of the Society's reorganization in the rapidly changing field of
      head and neck surgery and details how AHNS members can harness this change to
      direct the future of their field. Specifically, AHNS members' vital roles as
      technically proficient surgeons, surgical team members, researchers, teachers,
      and leaders within an evolving medical system are explored.

PMID- 30286219
TI  - Association of Disorganization of Retinal Inner Layers With Visual Acuity
      Response to Anti-Vascular Endothelial Growth Factor Therapy for Macular Edema
      Secondary to Retinal Vein Occlusion.
AB  - Importance: Disorganization of retinal inner layers (DRIL) has demonstrated
      significant correlations with visual acuity (VA) in center-involved diabetic
      macular edema. In patients with retinal vein occlusion (RVO) and secondary
      macular edema, DRIL may be a useful biomarker in determining VA outcomes.
      Objective: To examine whether DRIL at baseline and after treatment is associated
      with VA in RVO. Design, Setting, and Participants: A retrospective review of
      records of 147 patients 18 years or older with treatment-naive branch RVO (BRVO),
      central RVO (CRVO), or hemispheric RVO (HRVO), with a minimum of 12 months of
      follow-up, who presented to a tertiary ophthalmic center from December 1, 2010,
      to January 1, 2016, was conducted. Data collection continued through January
      2017. Exclusion criteria included active confounding retinal or ocular disease,
      history of pars plana vitrectomy, or prior intravitreal injections. Two masked
      graders calculated a DRIL score based on DRIL presence in 3 predefined regions on
      spectral-domain optical coherence tomography at baseline, 6 months, and 12
      months. A third masked grader was used for discrepancies. Exposures: Anti
      vascular endothelial growth factor (AVF) therapy (ranibizumab, aflibercept, or
      bevacizumab) determined by the treating physician. Main Outcomes and Measures:
      The DRIL score at baseline for determining VA outcomes and correlation of VA with
      changes in DRIL burden in response to AVF therapy. Results: In the 147 patients
      (mean [SD] age, 68.9 [13.1] years; 75 [51.0%] female), baseline DRIL was seen in
      91 eyes (61.9%). In the BRVO group but not the CRVO group, baseline DRIL was
      associated with lower baseline Early Treatment Diabetic Retinopathy Study (ETDRS)
      score (score of 66.7 for no DRIL vs 54.6 for DRIL, P = .002). Absence of DRIL at
      baseline in the CRVO/HRVO group correlated with greater VA gains at 6 months,
      adjusting for baseline VA (score change of 19.50 for no DRIL vs 12.72 for DRIL; P
      = .04). During 12 months, continued DRIL presence in BRVO was associated with
      less VA gain up to 6 months (score change of 6.2 for the DRIL increase group vs
      18.6 for the DRIL decrease group vs 2.9 for the DRIL stable group; P = .02).
      Increasing DRIL scores in CRVO/HRVO were associated with reduced VA improvement
      at 6 months (score change of -0.12 for the DRIL increase group vs 16.90 for the
      DRIL decrease group vs 8.45 for the DRIL stable group; P = .002) and 12 months
      (score change of -1.91 for the DRIL increase group vs 17.83 for the DRIL decrease
      group vs 6.97 for the DRIL stable group; P < .001). Conclusions and Relevance:
      Baseline DRIL presence and DRIL burden changes with AVF therapy for macular edema
      secondary to RVO may be useful biomarkers of ETDRS score improvements.

PMID- 30286220
TI  - Atypical White Dot Syndrome in an Older Man.

PMID- 30286221
TI  - The Role of Otolaryngologists in Eradicating Human Papillomavirus-Reply.

PMID- 30286222
TI  - Sense of Effort and Fatigue Associated With Talking After Total Laryngectomy.
AB  - Purpose: Sense of effort and fatigue associated with talking was compared in
      individuals with and without a total laryngectomy. Method: An online survey of
      individuals using tracheoesophageal speech (TES; n = 222), electrolaryngeal
      speech (ELS; n = 132), esophageal speech (n = 41), and laryngeal speech (LS; n =
      112) asked about 3 domains of effort when talking: frequency of occurrence,
      withdrawal from talking, and location in the body. Three aspects of fatigue were
      explored: frequency of occurrence, fatigue type, and duration of talking before
      fatigue. Results: Alaryngeal groups reported significantly more talking-related
      effort and fatigue than the LS group. Sixty-three percent of all respondents
      indicated that effort caused them to talk less, with no group differences on this
      item. Significantly more effort was localized to the lips and tongue by ELS
      compared with TES and LS groups. Both the ELS and TES groups had higher
      shoulder/arm effort when talking compared with the esophageal speech and LS
      groups. ELS respondents reported less fatigue than the TES group. When fatigue
      was present, the TES group had more physical and less mental fatigue than the ELS
      group. The duration of talking before experiencing fatigue was significantly
      shorter for the alaryngeal groups compared with the LS group. Conclusions: Effort
      and fatigue associated with talking are a common report for individuals using
      alaryngeal speech. The location of effort within the body and the type of fatigue
      experienced vary to some extent across alaryngeal speaking methods.

PMID- 30286223
TI  - Implications of Zero Suicide for Suicide Prevention Research.

PMID- 30286224
TI  - Immune Checkpoint Inhibitor Toxicity in 2018.

PMID- 30286225
TI  - Bilateral Lower Extremity Skin Eruptions in an HIV-Positive Man Receiving
      Pembrolizumab Monotherapy for Non-Small Cell Lung Cancer.

PMID- 30286226
TI  - Changes in the Incidence of Eye Trauma Hospitalizations in the United States From
      2001 Through 2014.
AB  - Importance: Eye trauma is a common cause of vision loss and a substantial public
      health problem. Objective: To determine the changes in the incidence of eye
      trauma hospitalizations in the United States and compare the demographics of
      affected patients and outcomes of eye trauma as a primary or secondary admitting
      diagnosis. Design, Setting, and Participants: This retrospective longitudinal
      cohort study used the National Inpatient Sample, a representative sample of all
      US community hospitals, to determine the incidence, characteristics, and causes
      of primary and secondary inpatient eye trauma admissions from 2001 through 2014.
      All inpatients with relevant diagnoses were included. Linear regression was used
      to estimate changes in incidence. Logistic regression was used to compare
      demographics and outcomes between primary and secondary diagnoses, including age,
      sex, race, income, primary payer, region, year of admission, length of stay,
      cost, and disposition at discharge. Exposures: Eye trauma. Main Outcomes and
      Measures: Incidence and characteristics of inpatient primary and secondary eye
      trauma. Results: From 2001 to 2014, there were an estimated 939 608 inpatient
      admissions (of whom 556 886 were male patients [59.3%]; overall mean [SD] age,
      49.4 [25.2] years) in the United States because of eye trauma diagnoses, with 778
      967 of these (82.9%) as a secondary diagnosis. The incidence of primary eye
      trauma decreased from 3.9 to 3.0 per 100 000 population (difference, 0.9 [95% CI,
      0.2-1.6] per 100 000 population; P = .001). The incidence of eye trauma as a
      secondary admitting diagnosis increased from 14.5 to 19.0 per 100 000 population
      (difference, 4.5 [95% CI, 1.9-7.2] per 100 000 population; P = .004). This was
      largely attributed to an increasing number of falls in individuals older than 65
      years. The most frequent diagnosis was orbital fracture (64 149 [39.9%]) for
      primary trauma and contusion of eye and adnexa (19 301 [37.8%]) for secondary
      trauma. Primary trauma was more common in children (adjusted odds ratio [aOR],
      2.21 [95% CI, 2.09-2.32]) and adolescents (aOR, 1.25 [95% CI, 1.19-1.32]) than
      adults (reference), African American individuals (aOR, 1.89 [95% CI, 1.81-1.97])
      and Hispanic individuals (aOR, 1.52 [95% CI, 1.45-1.59]) than white individuals,
      and uninsured patients (aOR, 1.14 [95% CI, 1.07-1.22]) and those receiving
      Medicaid (aOR, 1.12 [95% CI, 1.05-1.19]) than Medicare beneficiaries. Patients
      with a primary diagnosis were more likely to have a stay of less than 3 days
      (patients with a primary diagnosis: 101 796 [63.4%]; secondary diagnosis: 274 538
      [35.2%]), more likely to have costs in the lowest quartile (patients with a
      primary diagnosis: 51 212 [31.9%]; secondary diagnosis: 166 260 [21.3%]), and
      less likely to die (patients with a primary diagnosis: 526 [0.3%]; secondary
      diagnosis: 20 929 [2.7%]). Conclusions and Relevance: These findings suggest that
      the increasing number of falls in individuals older than 65 years and the high
      risk of primary eye trauma in populations such as children and adolescents
      warrant the development and implementation of effective preventive strategies.
      Many of these patients are seen in ophthalmology practices where proactive risk
      assessment and counseling can play a critical role.

PMID- 30286227
TI  - Association of Transient Colorblindness With Sildenafil and Tadalafil.

PMID- 30286228
TI  - Accuracy of Freely Available Information About Rhegmatogenous Retinal Detachment
      on the Internet.

PMID- 30286229
TI  - Cognitive Impairment Among Older Patients With Hematologic Cancers-Reply.

PMID- 30286231
TI  - Long Live Neutrophil.

PMID- 30286230
TI  - Identification of Baseline Characteristics Associated With Development of
      Depression Among Patients With Head and Neck Cancer: A Secondary Analysis of a
      Randomized Clinical Trial.
AB  - Importance: Patients with head and neck cancer (HNC) experience increased risk of
      depression and compromised quality of life. Identifying patients with HNC at risk
      of depression can help establish targeted interventions. Objective: To identify
      factors that may be associated with the development of moderate or severe
      depression during treatment of HNC. Design, Setting, and Participants: This is a
      retrospective, ad hoc, secondary analysis of prospectively collected data from a
      randomized, double-blind, placebo-controlled clinical trial. Patients were
      screened at academic- and community-based tertiary care HNC centers from January
      2008 to December 2011. Of the 125 evaluable patients with stages II through IV
      HNC but without baseline depression, 60 were randomized to prophylactic
      antidepressant escitalopram oxalate and 65 to placebo at the time of the initial
      diagnosis. Data analyses were conducted from May 2016 to April 2017. Main
      Outcomes and Measures: Depression outcomes were measured using Quick Inventory of
      Depressive Symptomatology-Self Report (QIDS-SR) scores (range, 0-27 with a score
      of 11 or higher indicative of moderate or greater depression). Factors that may
      be associated with development of moderate or severe depression were assessed,
      including patient demographics; cancer site and stage; primary treatment modality
      (surgery or radiotherapy); history of depression or other psychiatric diagnosis;
      previous treatment of depression or suicide attempt, family history of
      depression, suicide, or suicide attempt; and baseline score on the QIDS-SR and
      clinician-rated QIDS instruments. Participants were stratified by study site,
      sex, cancer stage (early [stage II] vs advanced [stage III or IV]), primary
      modality of treatment (radiotherapy with or without chemotherapy vs surgery with
      or without radiotherapy), and randomization to placebo or escitalopram and
      balanced within these strata. Results: The mean (SD) age of the 148 patients in
      the study population was 63.0 (11.9) years; 118 (79.7%) were men, and 143 (96.6%)
      were white. In the evaluable population of 125 patients, receiver operating
      characteristic analyses assessing the area under the curve for baseline QIDS-SR
      score (0.816; 95% CI, 0.696-0.935) and for initial radiotherapy-based treatment
      (0.681, 95% CI, 0.552-0.811) suggested that these 2 variables were associated
      with the likelihood of developing moderate or greater depression during the study
      period among patients who did not receive prophylactic antidepressants. The
      diagnostic sensitivity for identifying patients at risk of depression using the
      baseline QIDS-SR score improved to 100% at a threshold of 2 from 94% at a
      threshold of 4. Conclusions and Relevance: Baseline symptoms and initial
      radiotherapy-based treatment may be associated with development of moderate or
      greater depression in patients with HNC. Patients with QIDS-SR baseline scores of
      2 or higher may benefit the most from pharmacologic prophylaxis of depression.

PMID- 30286232
TI  - Characteristics of Speech Rate in Children With Cerebral Palsy: A Longitudinal
      Study.
AB  - Purpose: The purpose of this longitudinal study was to examine the effect of time
      and sentence length on speech rate and its characteristics, articulation rate and
      pauses, within 2 groups of children with cerebral palsy (CP). Method: Thirty-four
      children with CP, 18 with no speech motor involvement and 16 with speech motor
      involvement, produced sentences of varying lengths at 3 time points that were 1
      year apart (mean age = 56 months at first time point). Dependent measures
      included speech rate, articulation rate, proportion of time spent pausing, and
      average number and duration of pauses. Results: There were no significant effects
      of time. For children with no speech motor involvement, speech rate increased
      with longer sentences due to increased articulation rate. For children with
      speech motor involvement, speech rate did not change with sentence length due to
      significant increases in the proportion of time spent pausing and average number
      of pauses in longer sentences. Conclusions: There were no significant age-related
      differences in speech rate in children with CP regardless of group membership.
      Sentence length differentially impacted speech rate and its characteristics in
      both groups of children with CP. This may be due to cognitive-linguistic and/or
      speech motor control factors.

PMID- 30286233
TI  - Disorganization of Retinal Inner Layers and the Importance of Setting Boundaries.

PMID- 30286234
TI  - Analysis of Cervical Angle in the Submental Muscular Medialization and Suspension
      Procedure.
AB  - Importance: The submental muscular medialization and suspension (SMMS) procedure
      is an option for addressing an obtuse cervical angle in select patients vs the
      use of traditional rhytidectomy techniques. Objective: To compare the change in
      position of the cervical point between groups undergoing SMMS vs the traditional
      rhytidectomy technique. Design, Setting, and Participants: A retrospective review
      was performed of 141 patients undergoing rhytidectomy in an accredited private
      surgery center between January 1, 2013, and December 31, 2014, comparing cervical
      point depth between patients undergoing SMMS vs those undergoing traditional
      rhytidectomy with platysma plication. Statistical analysis was performed from
      November 11, 2017, to January 5, 2018. Interventions: Patients underwent either
      SMMS or traditional rhytidectomy with platysma plication. Main Outcomes and
      Measures: The primary end point was change in the cervical point distance between
      preoperative and postoperative standardized profile photos. Results: A total of
      141 patients were included in the analysis. A cohort of 46 patients (43 women and
      3 men; mean age, 63.5 years [range, 49.0-79.0 years]) underwent neck contouring
      with the SMMS technique and a cohort of 95 patients (90 women and 5 men; mean
      age, 61.0 years [range, 48.0-73.0 years]) underwent traditional rhytidectomy with
      platysmaplasty. The cervical point distance of the SMMS cohort had a mean (SD)
      postoperative increase of 2.0 (1.05) cm (95% CI, 1.73-2.28; P < .001) compared
      with 0.78 (0.82) cm in the traditional rhytidectomy cohort (95% CI, 0.54-1.02; P
      < .001). Conclusions and Relevance: The results of this study suggest that
      submental muscular medialization and suspension appears to be an effective option
      to address the obtuse neck in select patients. Level of Evidence: 3.

PMID- 30286235
TI  - Association Between Aspirin Use and Risk of Hepatocellular Carcinoma.
AB  - Importance: Prospective data on the risk of hepatocellular carcinoma (HCC)
      according to dose and duration of aspirin therapy are limited. Objective: To
      examine the potential benefits of aspirin use for primary HCC prevention at a
      range of doses and durations of use within 2 prospective, nationwide populations.
      Design, Setting, and Participants: Pooled analysis of 2 prospective US cohort
      studies: the Nurses' Health Study and the Health Professionals Follow-up Study.
      Data were accessed from November 1, 2017, through March 7, 2018. A total of 133
      371 health care professionals who reported data on aspirin use, frequency,
      dosage, and duration of use biennially since 1980 in women and 1986 in men were
      included. Individuals with a cancer diagnosis at baseline (except nonmelanoma
      skin cancer) were excluded. Main Outcomes and Measures: Cox proportional hazards
      regression models were used to calculate multivariable adjusted hazard ratios
      (HRs) and 95% CIs for HCC. Results: Of the 133 371 participants, 87 507 were
      women and 45 864 were men; in 1996, the median time of follow-up, the mean (SD)
      age was 62 (8) years for women and 64 (8) years for men. Over more than 26 years
      of follow-up encompassing 4 232 188 person-years, 108 incident HCC cases (65
      women, 43 men) were documented. Compared with nonregular use, regular aspirin use
      (>=2 standard-dose [325-mg] tablets per week) was associated with reduced HCC
      risk (adjusted HR, 0.51; 95% CI, 0.34-0.77). This benefit appeared to be dose
      related: compared with nonuse, the multivariable-adjusted HR for HCC was 0.87
      (95% CI, 0.51-1.48) for up to 1.5 standard-dose tablets per week, 0.51 (95% CI,
      0.30-0.86) for more than 1.5 to 5 tablets per week, and 0.49 (95% CI, 0.28-0.96)
      for more than 5 tablets per week (P for trend = .006). Significantly lower HCC
      risk was observed with increasing duration (P for trend = .03); this decrease was
      apparent with use of 1.5 or more standard-dose aspirin tablets per week for 5 or
      more years (adjusted HR, 0.41; 95% CI, 0.21-0.77). In contrast, use of nonaspirin
      nonsteroidal anti-inflammatory drugs was not significantly associated with HCC
      risk (adjusted HR, 1.09; 95% CI, 0.78-1.51). Conclusions and Relevance: This
      study suggests that regular, long-term aspirin use is associated with a dose
      dependent reduction in HCC risk, which is apparent after 5 or more years of use.
      Similar associations were not found with nonaspirin NSAIDs. Further research
      appears to be needed to clarify whether aspirin use represents a feasible
      strategy for primary prevention against HCC.

PMID- 30286237
TI  - Cognitive Behavioral Therapy for Tinnitus Unbound.

PMID- 30286236
TI  - Erectile Dysfunction in Male Survivors of Childhood Cancer.

PMID- 30286238
TI  - Effectiveness of Guided Internet-Based Cognitive Behavioral Therapy vs Face-to
      Face Clinical Care for Treatment of Tinnitus: A Randomized Clinical Trial.
AB  - Importance: Accessible clinical care is not always available to individuals with
      distressing tinnitus. Internet-based cognitive behavioral therapy has the
      potential to increase access to evidence-based services that manage tinnitus.
      Research comparing the effectiveness of this internet-based intervention with
      face-to-face care is required. Objective: To evaluate whether an internet-based
      cognitive behavioral therapy intervention is at least as effective as established
      individualized face-to-face clinical care in reducing tinnitus distress and
      tinnitus-related difficulties. Design, Setting, and Participants: A randomized,
      multicenter, 2-arm parallel group, noninferiority trial with 2-month follow-up
      was performed between October 4, 2016, and July 14, 2017. Invited to participate
      were 374 adults based in the United Kingdom who had been referred to their local
      tinnitus clinics because of bothersome tinnitus. The experimental group received
      the internet-based intervention online, and the active control group underwent
      the usual face-to-face tinnitus care at 1 of 3 UK-based National Health Service
      hospitals. Participants were randomly assigned (1:1) to either intervention using
      variable permuted block sizes of 4 and 6. Of 92 participants who were randomized
      (46 each in the experimental and control groups), 88 participants completed the
      assessment immediately after intervention and 74 participants completed the
      follow-up assessment. Interventions: Participants were randomized to receive
      either 8 weeks of guided internet-based cognitive behavioral therapy or a mean of
      2 to 3 individualized face-to-face appointments in a tinnitus clinic. Main
      Outcomes and Measures: The primary outcome was a change in tinnitus distress
      (assessed by the Tinnitus Functional Index). Secondary assessment measures were
      included for insomnia, anxiety, depression, hearing disability, hyperacusis,
      cognitive failures, and satisfaction with life. Results: Of 92 patients overall,
      55 (60%) were men with a mean (SD) age of 52.96 (12.07) years and mean (SD)
      tinnitus duration of 6.54 (9.25) years. The between-group difference in the
      Tinnitus Functional Index scores after intervention were 5.18 (95% CI, -4.17 to
      14.53) at the initial assessment and 5.52 (95% CI, -4.60 to 15.61) at follow-up;
      both differences were within the noninferiority margin of 13 points for the lower
      95% CI. For the secondary outcomes, only outcomes for insomnia fell outside the
      noninferiority margin, both after intervention and at follow-up, favoring
      internet-based cognitive behavioral therapy. Conclusions and Relevance: This is
      the first trial, to our knowledge, to compare an internet-based intervention with
      standard individualized face-to-face care for tinnitus. It revealed that both
      interventions are equally effective for reducing tinnitus distress and most
      tinnitus-related difficulties. Trial Registration: ClinicalTrials.gov identifier:
      NCT02665975.

PMID- 30286240
TI  - The Role of Otolaryngologists in Eradicating Human Papillomavirus.

PMID- 30286239
TI  - Association of Analgesic Use With Risk of Ovarian Cancer in the Nurses' Health
      Studies.
AB  - Importance: Ovarian cancer is a highly fatal malignant neoplasm with few
      modifiable risk factors. Case-control studies have reported a modest reduced risk
      of ovarian cancer among women who frequently use aspirin or regularly use low
      dose aspirin. Objective: To evaluate whether regular aspirin or nonaspirin
      nonsteroidal anti-inflammatory drug (NSAID) use and patterns of use are
      associated with lower ovarian cancer risk. Design, Setting, and Participants:
      This cohort study analyzed NSAID use and ovarian cancer diagnosis data from 2
      prospective cohorts, 93 664 women in the Nurses' Health Study (NHS), who were
      followed up from 1980 to 2014, and 111 834 in the Nurses' Health Study II
      (NHSII), who were followed up from 1989 to 2015. Follow-up was completed on June
      30, 2014, for the NHS and June 30, 2015, for NHSII. Data were analyzed from June
      13, 2016, to September 18, 2017. Exposures: For each analgesic type (aspirin, low
      dose aspirin, nonaspirin NSAIDs, and acetaminophen), timing, duration, frequency,
      and number of tablets used were evaluated; exposure information was updated every
      2 to 4 years. Main Outcomes and Measures: Cox proportional hazards models were
      used to estimate hazard ratios (HRs) and 95% CIs for associations of aspirin,
      nonaspirin NSAIDs, and acetaminophen with risk of epithelial ovarian cancer. All
      statistical tests were 2-sided, with a significance level of .05. Results: In the
      NHS, the mean (SD) age at baseline (1980) was 45.9 (7.2) years, and 93% of
      participants identified as non-Hispanic white. In the NHSII, the mean age at
      baseline (1989) was 34.2 (4.7) years, and 92% identified as non-Hispanic white.
      Among the 205 498 women in both cohorts, there were 1054 cases of incident
      epithelial ovarian cancer. Significant associations between aspirin and ovarian
      cancer risk were not observed when current vs nonuse of any aspirin was evaluated
      regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). However, when low-dose (<=100
      mg) and standard-dose (325-mg) aspirin were evaluated separately, an inverse
      association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96), but no
      association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49) was observed.
      Current use of nonaspirin NSAIDs was positively associated with risk of ovarian
      cancer compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and significant
      positive trends for duration of use (P = .02 for trend) and cumulative average
      tablets per week (P = .03 for trend) were observed. There were no clear
      associations for the use of acetaminophen. Conclusions and Relevance: These
      results appear to be consistent with case-control studies that show a reduced
      risk of ovarian cancer among regular users of low-dose aspirin. An increased risk
      of ovarian cancer with long-term high-quantity use of other analgesics,
      particularly nonaspirin NSAIDs, was observed, although this finding requires
      confirmation.

PMID- 30286241
TI  - An Unusual Complication of Ocular Trauma in a 10-Year-Old Girl.

PMID- 30286243
TI  - Incorrect Orientation of Figure 2.

PMID- 30286242
TI  - Pilot Study of Audiometric Patterns in Fuchs Corneal Dystrophy.
AB  - Purpose: Although Fuchs corneal dystrophy (FCD) is considered an eye disease, a
      small number of studies have identified genes related to both FCD and hearing
      loss. Whether FCD is related to hearing loss is unknown. Method: This is a case
      control study comparing pure-tone audiometry hearing thresholds in 180 patients
      with FCD from a hospital-based ophthalmology clinic with 2,575 population-based
      controls from a nationally representative survey, the National Health and
      Nutrition Examination Survey (from cycles 2005-06 and 2009-10). Generalized
      estimating equations were used to compare mean better-hearing ear thresholds in
      the 2 groups adjusted for age, sex, race, and noise exposure. Results: Patients
      with FCD had higher hearing thresholds (worse hearing) in lower frequencies (mean
      difference at 0.5 kHz = 3.49 dB HL) and lower hearing thresholds (better hearing)
      in higher frequencies (difference at 4 kHz = -4.25 dB HL) compared with
      population-based controls. Conclusion: In the first study to use objectively
      measured hearing, FCD was associated with poorer low-frequency and better high
      frequency audiometric thresholds than population controls. Further studies are
      needed to characterize this relationship.

PMID- 30286244
TI  - Associations Between Manual Dexterity and Language Ability in School-Age
      Children.
AB  - Purpose: We aimed to determine whether individual differences in manual dexterity
      are associated with specific language skills (nonword repetition, receptive
      vocabulary, and receptive grammar) after controlling for nonverbal abilities
      (visual-spatial working memory and intelligence). Method: We assessed manual
      dexterity using the pegboard task and examined relationships with verbal and
      nonverbal abilities in a diverse community sample of children (N = 63, mean age =
      8;2 [year;months], range: 6;0-10;8) varying in language ability (Comprehensive
      Evaluation of Language Fundamentals-Fourth Edition core language score M = 105,
      range: 62-126; Semel, Wiig, & Secord, 2003). Results: Correlational analyses
      indicated significant relationships between manual dexterity and performance on
      tests of nonword repetition, receptive vocabulary, receptive grammar, and
      nonverbal intelligence, after controlling for multiple comparisons. In regression
      analyses, manual dexterity remained a significant predictor of nonword repetition
      after controlling for nonverbal abilities and age. In contrast, manual dexterity
      was no longer significant in predicting receptive vocabulary or grammar when
      nonverbal intelligence was included as a factor in the model. Conclusions: These
      findings build on prior work implicating poor fine motor control in child
      language disorders by identifying a robust relationship between manual dexterity
      and nonword repetition. Relationships between manual dexterity and receptive
      language abilities appear to be indirect and mediated by nonword repetition. For
      clinicians, the results underscore the importance of screening children with poor
      fine motor control for concomitant language impairments.

PMID- 30286245
TI  - Service Provision for Children Who Are Hard of Hearing at Preschool and
      Elementary School Ages.
AB  - Purpose: To characterize preschool and school services for children who are hard
      of hearing (CHH), we described service setting, amount, and configuration and
      analyzed the relationship between service receipt and student hearing levels and
      language scores. Characteristics of professionals providing services were
      described and then used to predict level of comfort with skills supporting
      listening and spoken language. The amount of provider communication with
      children's audiologists was also investigated. Method: Participants included
      parents of CHH (preschool n = 174; school n = 155) and professionals (preschool n
      = 133; school n = 104) who completed interviews and questionnaires as part of a
      longitudinal study. Children's hearing, speech, and language data were collected
      from annual testing and analyzed in relation to service data. Results: A majority
      (81%) of preschool-age CHH received services. Children were more likely to be in
      a preschool for children who are deaf or hard of hearing (CDHH) or exceptional
      children than a general education preschool. By elementary school, 70% received
      services, nearly all in general education settings. Sessions averaged twice a
      week for a total of approximately 90 min. Children who no longer received
      services performed significantly better on speech/language measures than those
      who received services, regardless of service setting. Professionals were
      primarily speech-language pathologists (SLPs) and teachers of CDHH. SLPs reported
      significantly less comfort with skills involving auditory development and hearing
      technologies and less frequent communication with the child's audiologists than
      teachers of CDHH. Overall communication with audiologists was more frequent in
      the preschool years. Conclusions: As preschool-age CHH transition into school,
      the majority continue to qualify for services. Congruent with national trends,
      school-age CHH in the Outcomes of Children with Hearing Loss study were most
      often in general education settings. Without specialized preprofessional or
      postgraduate training, SLPs and teachers of CDHH did not report comfort with all
      the skills critical to developing listening and spoken language. This finding
      supports the need for increased implementation of interprofessional practice
      among SLPs and teachers of CDHH, as well as audiologists, to best meet the needs
      unique to this population.

PMID- 30286246
TI  - Explaining Reading Comprehension in Children With Developmental Language
      Disorder: The Importance of Elaborative Inferencing.
AB  - Purpose: Reading comprehension is a key indicator of academic and psychosocial
      outcomes. Children with developmental language disorder (DLD) tend to find
      reading comprehension challenging. This study aimed to explore the literal and
      inferential (cohesive, elaborative, and lexical) comprehension of children with
      DLD, their typically developing (TD) peers, and, uniquely, a group of children
      with low language (LL) proficiency. Method: Children aged 10-11 years with either
      typical development (n = 16), LL proficiency (n = 14), or DLD (n = 14) were
      recruited from 8 primary schools. They completed a battery of standardized
      language and literacy assessments. Responses to literal and inferential questions
      on the Wechsler Individual Achievement Test-Second UK Edition (Wechsler, 2005)
      were analyzed. Results: A disproportionate difficulty in answering inferential
      relative to literal questions was found for the DLD group compared to the LL and
      TD groups. Children with DLD were significantly poorer at elaborative inferencing
      than both their peers with LL proficiency and TD peers, but there were no group
      differences in cohesive or lexical inferencing. There was a significant positive
      association between inferencing ability and vocabulary knowledge, single word
      reading accuracy, grammatical skill, and verbal working memory. The importance of
      single word reading accuracy was especially evident as a partial mediator of the
      relationship between vocabulary knowledge and inferencing ability. Conclusions:
      These results indicate that interventions targeting the reading comprehension of
      children with DLD should focus on elaborative inferencing skill. There are also
      clinical implications as the development of new standardized assessments
      differentiating between inference types is called for.

PMID- 30286247
TI  - Changes in English Past Tense Use by Bilingual School-Age Children With and
      Without Developmental Language Disorder.
AB  - Purpose: The purpose of this study is to examine changes in English past tense
      accuracy and errors among Spanish-English bilingual children with typical
      development (TD) and developmental language disorder (DLD). Method: Thirty-three
      children were tested before and after 1 year to examine changes in clinically
      relevant English past tense errors using an elicited production task. A mixed
      model linear regression using age as a continuous variable revealed a robust
      effect for age. A 4-way repeated-measures analysis of variance was conducted with
      age (young, old) and language ability group (TD, DLD) as between-subjects
      variables, time (Time 1, Time 2) and verb type (regular, irregular, and novel
      verbs) as within-subject variables, and percent accuracy as the dependent
      variable. Subsequently, a 4-way repeated-measures analysis of variance was
      conducted to measure the overall distribution of verb errors across 2 time
      points. Results: Overall, children produced regular and novel verb past tense
      forms with higher accuracy than irregular past tense verbs in an elicitation
      task. Children with TD were more accurate than children with DLD. Younger
      children made more improvement than older children from Time 1 to Time 2,
      especially in the regular and novel verb conditions. Bare stem and
      overregularization were the most common errors across all groups. Errors
      consisting of stem + ing were more common in children with DLD than those with TD
      in the novel verb condition. Discussion: Contrary to an earlier report (Jacobson
      & Schwartz, 2005), the relative greater difficulty with regular and novel verbs
      was replaced by greater difficulty for irregular past tense, a pattern consistent
      with monolingual impairment. Age was a contributing factor, particularly for
      younger children with DLD who produced more stem + ing errors in the novel verb
      condition. For all children, and particularly for those with DLD, an extended
      period for irregular past tense learning was evident. The results support a usage
      based theory of language acquisition and impairment.

PMID- 30286248
TI  - Factors Associated With Self-Reported Hearing Aid Management Skills and
      Knowledge.
AB  - Purpose: Hearing aid management describes the skills and knowledge required for
      the handling, use, care, and maintenance of the hearing aid. The importance of
      hearing aid management skills and knowledge is evidenced by their association
      with hearing aid outcomes. However, the nature of this association and the
      influence of participant factors on this association are unknown. Accordingly,
      the aims of the current study were to (a) investigate participant factors that
      influence hearing aid management skills and knowledge and (b) investigate the
      impact of hearing aid management skills and knowledge on hearing aid outcomes.
      Method: Factors associated with hearing aid management skills and knowledge were
      investigated through an e-mail- and paper-based self-report survey, including the
      Hearing Aid Skills and Knowledge Inventory (Bennett, Meyer, Eikelboom, & Atlas,
      2018b) and the International Outcomes Inventory for Hearing Aids (Cox &
      Alexander, 2002). The study sample included 518 adult hearing aid owners, ranging
      in age from 18 to 97 years (M = 71 years, SD = 14 years), 61% male and 39%
      female, recruited from seven hearing clinics across Australia. Results:
      Participant factors found to be associated with hearing aid skills and knowledge
      included participants' age, gender, style of hearing aid, age of current hearing
      aid, and total years of hearing aid ownership. Higher levels of hearing aid
      management skills and knowledge were found to be associated with better hearing
      aid outcomes, specifically higher self-reported satisfaction with hearing aids,
      perceived benefit from hearing aids, and overall outcome of the hearing aid
      fitting as evaluated by the International Outcomes Inventory for Hearing Aids.
      Conclusions: Hearing aid management difficulties were greatest for older people,
      women, and owners of behind-the-ear style of hearing aids, suggesting that
      clinicians need to be cognizant of the additional needs for these three groups.
      The positive association between hearing aid outcomes and hearing aid skills and
      knowledge emphasizes the importance of education and training on hearing aid
      management for successful aural rehabilitation.

PMID- 30286249
TI  - Integrative Analysis of Programmed Death-Ligand 1 DNA, mRNA, and Protein Status
      and their Clinicopathological Correlation in Diffuse Large B-cell Lymphoma.
AB  - AIMS: The Protein expression of Programmed Death-Ligand 1 (PD-L1) has been
      recognized a poor prognostic biomarker in diffuse large B-cell lymphoma (DLBCL).
      We aim to detect PD-L1 DNA and mRNA status, and explore whether they contribute
      to protein expression and their clinicopathological correlation in DLBCL. METHODS
      AND RESULTS: In the study, we detected PD-L1 status in three different levels by
      Fluorescence in situ hybridization, RNA in situ hybridization and
      immunohistochemistry in 287 DLBCL samples with follow-ups, respectively. Their
      correlation and clinical pathological relevance was further analyzed. Our results
      showed that 1.7% (3/175) patients had PD-L1 amplification, 19.9% (57/287) PD-L1
      mRNA high expression and 11.8% (34/287) high protein expression. Both mRNA and
      protein high expression of PD-L1 was significantly elevated in non-GCB than that
      in GCB DLBCL (P<0.05). In addition, the patients with PD-L1 mRNA or protein high
      expression but not DNA amplification have significantly poorer overall survival
      (OS) than that with PD-L1 low expression (P<0.05). Furthermore, we found that PD
      L1 mRNA and protein expression are highly correlated (P=0.012), which was
      observed in all three samples with PD-L1 DNA amplification. CONCLUSIONS: PD-L1
      DNA amplification is a rare event, PD-L1 mRNA mainly contribute to the protein
      high expression, and the latter two will serve as important biomarkers for
      predicting prognosis and selecting patients for immunotherapy in DLBCL. This
      article is protected by copyright. All rights reserved.

PMID- 30286251
TI  - Defining and Measuring Nursing Home Placement.

PMID- 30286250
TI  - Lower body negative pressure to safely reduce intracranial pressure.
AB  - KEY POINTS: During long-term missions, some astronauts experience structural and
      functional changes of the eyes and brain which resemble signs/symptoms
      experienced by patients with intracranial hypertension. Weightlessness prevents
      the normal cerebral volume and pressure 'unloading' associated with upright
      postures on Earth, which may be part of the cerebral and ocular pathophysiology.
      By placing the lower body in a negative pressure device (LBNP) that pulls fluid
      away from cranial compartments, we simulated effects of gravity and significantly
      lowered pressure within the brain parenchyma and ventricle compartments.
      Application of incremental LBNP demonstrated a non-linear dose-response curve,
      suggesting 20 mmHg LBNP as the optimal level for reducing pressure in the brain
      without impairing cerebral perfusion pressure. This non-invasive method of
      reducing pressure in the brain holds potential as a countermeasure in space as
      well as having treatment potential for patients on Earth with traumatic brain
      injury or other pathology leading to intracranial hypertension. ABSTRACT:
      Patients with elevated intracranial pressure (ICP) exhibit neuro-ocular symptoms
      including headache, papilloedema and loss of vision. Some of these symptoms are
      also present in astronauts during and after prolonged space-flight where lack of
      gravitational stress prevents daily lowering of ICP associated with upright
      posture. Lower body negative pressure (LBNP) simulates the effects of gravity by
      displacing fluid caudally and we hypothesized that LBNP would lower ICP without
      compromising cerebral perfusion. Ten cerebrally intact volunteers were included:
      six ambulatory neurosurgical patients with parenchymal ICP-sensors and four
      former cancer patients with Ommaya-reservoirs to the frontal horn of a lateral
      ventricle. We applied LBNP while recording ICP and blood pressure while supine,
      and during simulated intracranial hypertension by 15 degrees  head-down tilt.
      LBNP from 0 to 50 mmHg at increments of 10 mmHg lowered ICP in a non-linear dose
      dependent fashion; when supine (n = 10), ICP was decreased from 15 +/- 2 mmHg to
      14 +/- 4, 12 +/- 5, 11 +/- 4, 10 +/- 3 and 9 +/- 4 mmHg, respectively (P <
      0.0001). Cerebral perfusion pressure (CPP), calculated as mean arterial blood
      pressure at midbrain level minus ICP, was unchanged (from 70 +/- 12 mmHg to 67 +/
      9, 69 +/- 10, 70 +/- 12, 72 +/- 13 and 74 +/- 15 mmHg; P = 0.02). A 15 degrees 
      head-down tilt (n = 6) increased ICP to 26 +/- 4 mmHg, while application of LBNP
      lowered ICP (to 21 +/- 4, 20 +/- 4, 18 +/- 4, 17 +/- 4 and 17 +/- 4 mmHg; P <
      0.0001) and increased CPP (P < 0.01). An LBNP of 20 mmHg may be the optimal level
      to lower ICP without impairing CPP to counteract spaceflight-associated neuro
      ocular syndrome in astronauts. Furthermore, LBNP holds clinical potential as a
      safe, non-invasive method for lowering ICP and improving CPP for patients with
      pathologically elevated ICP on Earth.

PMID- 30286252
TI  - Immunohistochemistry of cytokeratin (CK) 5/6, CD44 and CK20 as prognostic
      biomarkers of non-muscle-invasive papillary upper tract urothelial carcinoma.
AB  - AIMS: Immunohistochemical (IHC) staining for cytokeratin (CK) 5/6, CD44 and CK20
      has been significantly associated with the prognosis of urinary bladder
      urothelial carcinoma, and probably reflects its molecular characteristics. We
      aimed to investigate the IHC-based subgroups and their prognostic effects on non
      muscle-invasive papillary upper tract urothelial carcinoma (UTUC). METHODS AND
      RESULTS: IHC staining for CK5/6, CK20 and CD44 was analysed in 211 patients with
      non-muscle-invasive papillary UTUC. Staining was classified as showing a
      negative, positive or normal pattern. We found that CK5/6-negative, CD44-negative
      and CK20-positive tumours were distinctly high-risk subgroups that were
      associated with high grade (CK5/6-negative, P < 0.001; CD44-negative, P < 0.001;
      CK20-positive, P = 0.017) and frequent intravesical recurrence (CK5/6-negative, P
      = 0.002). Using survival analysis with Kaplan-Meier and log-rank tests, we found
      that these IHC subgroups were correlated with poor progression-free (CK5/6
      negative, P = 0.001; CD44-negative, P = 0.009; CK20-positive, P = 0.031) and
      cancer-specific (CK5/6-negative, P = 0.009) survival. Furthermore, CK5/6
      negativity was an independent prognostic factor for shorter progression-free (P =
      0.009) and cancer-specific (P = 0.045) survival. CK5/6 improved Harrell's C
      indices for progression-free (0.68-0.77, P = 0.029) and cancer-specific (0.59
      0.77, P < 0.001) survival. When markers were combined, luminal-like subtypes
      showed poor prognoses. CONCLUSIONS: We demonstrated that IHC staining for CK5/6,
      CD44 and CK20 was significantly associated with the clinicopathological
      characteristics and prognoses of patients with non-muscle-invasive papillary
      UTUC. The IHC subgroups may be correlated with the molecular characteristics of
      non-muscle-invasive papillary UTUC.

PMID- 30286253
TI  - Corticospinal excitability during shortening and lengthening actions with
      incremental torque output.
AB  - NEW FINDINGS: What is the central question of this study? The relationship
      between motor unit recruitment and firing rate has been related to the size of
      the corticospinal output with variations in the nervous system gain during
      isometric contractions. However, corticospinal behaviour with incremental torque
      output might differ during anisometric contractions owing to differences in
      neural control of anisometric contraction types. What is the main finding and its
      importance? Corticospinal excitability during lengthening contractions was
      smaller compared with shortening but increased with incremental torque output in
      a similar manner between contraction types. The relationship between motor unit
      recruitment and firing rates is probably the main determinant of the size of an
      evoked response with variations in system gain. ABSTRACT: The modulation of motor
      evoked potentials (MEPs), an index of corticospinal excitability, has been shown
      to increase during isometric contractions with incremental torque output in
      accordance with the contribution between motor unit recruitment and firing rate
      of the muscle to increases in required torque output. However, the motor unit
      strategy of the muscle might not be the only factor influencing this behaviour,
      because differences in pre- and postsynaptic control have been reported between
      lengthening and shortening or isometric contractions. In 30 healthy adults, MEPs
      were elicited in tibialis anterior during shortening and lengthening contractions
      at 15, 25, 50 and 80% of contraction-type-specific maximal voluntary contraction
      torque. Background EMG activity increased progressively with greater torque
      output (P < 0.001) but was similar between contraction types (P = 0.162). When
      normalized to the maximal muscle response, MEPs were greater during shortening
      compared with lengthening contractions (P = 0.004) and increased stepwise with
      increased contraction intensities (P = 0.001). These data show an increase in
      corticospinal excitability with torque output from lower to higher contraction
      intensities, suggesting a greater contribution of motor unit recruitment to
      increased nervous system gain in the tibialis anterior. Despite differences in
      corticospinal control of shortening and lengthening contractions, the data
      suggest that the corticospinal responses to increases in torque output are not
      dependent on contraction type, because corticospinal excitability increased to a
      similar extent during shortening and lengthening actions. Thus, it is likely that
      the relationship between motor unit recruitment and firing rate of the muscle is
      the main determinant of corticospinal output with variations in nervous system
      gain.

PMID- 30286254
TI  - John D. Biggers (1923-2018).

PMID- 30286255
TI  - Highly enantioselective Michael addition of alpha-nitroacetate to alpha,beta
      unsaturated pyrazolamide catalyzed by a bifunctional squaramide.
AB  - A highly enantioselective (91- > 99% ee) Michael addition of alpha-nitroacetate
      to alpha,beta-unsaturated pyrazolamide was developed in the presence of a
      bifunctional squaramide. Satisfactory isolated yields (42%-99%) have been
      achieved with a wide range of alpha,beta-unsaturated pyrazolamides, albeit
      acceptor of this type displayed poor reactivity in the precedent reports. The
      adducts resulting from this protocol are useful synthetic intermediates for
      further synthetic modification.

PMID- 30286256
TI  - A new approach to pharmaceutical pricing based on patients' willingness to pay.
AB  - OBJECTIVES: Pharmaceutical pricing is an important and contentious issue in
      middle- and low-income countries. The present study evaluated a value-based
      pricing system for estimating the price of interferon-beta (IFN-beta). METHODS:
      Prices were estimated through the Willingness to Pay (WTP) system using the
      Discrete Choice Experiment (DCE) from the viewpoint of MS patients, levels of
      attributes and patients' willingness to pay for these attributes. RESULTS: The
      results indicate that the new approach to pricing medicines leads to more
      integrated prices than the current system. The current prices of four brands were
      higher than their pharmaceutical market price; the prices of other brands were
      consistent with it. CONCLUSION: Application of the proposed pricing system will
      help pharmaceutical companies make realistic price estimates of their products
      while accounting for patient preferences, which may enhance patients' adherence
      to treatment.

PMID- 30286257
TI  - Introduction to the Alaska Carbon Cycle Invited Feature.

PMID- 30286258
TI  - PLA-Based Triblock Copolymer Micelles Exhibiting Dual Acidic pH/Reduction
      Responses at Dual Core and Core/Corona Interface Locations.
AB  - Polylactide (PLA)-based amphiphilic block copolymers and their nanoassemblies
      designed with stimuli-responsive degradation (SRD) hold great potential as
      promising candidates for tumor-targeting drug delivery. However, most of the
      smart PLA-based nanoassemblies are designed to respond to a single stimulus
      (typically reduction or acidic pH). Herein, a new strategy is reported to
      synthesize PLA-based block copolymer micelles exhibiting dual SRD at dual
      locations (DL-DSRD). The strategy utilizes a combination of ring opening
      polymerization, controlled radical polymerization, and facile coupling reactions
      to synthesize an ABA-type PLA-based triblock copolymer with a hydrophilic
      polymethacrylate (A) and PLA (B) blocks. Incorporation of an acidic pH-responsive
      ketal linkage in the center of PLA block and reduction-responsive disulfide
      linkages at PLA/hydrophilic polymethacrylate blocks ensure the formation of smart
      nanoassemblies featured with ketal linkages in the PLA cores and disulfide
      linkages at core/corona interfaces, thus attaining DL-DSRD. Such dual acidic
      pH/reduction-responses at dual locations lead to not only shedding of coronas at
      interfaces but also destabilization of cores, resulting in the synergistic and
      accelerated release of encapsulated model drugs, compared with the single
      stimulus systems. These results, along with lower cytotoxicity, suggest that DL
      DSRD strategy can offer versatility in the development of tumor-targeting drug
      delivery nanocarriers.

PMID- 30286259
TI  - Adriamycin inhibits embryonic development in zebrafish through downregulation of
      Kruppel-like factor4.
AB  - Adriamycin is an effective anticancer drug used in a wide range of cancers.
      Anticancer drugs modulate oncogenes and nodal regulatory molecules that affect
      cell differentiation and organismal development. In this study, we explore the
      effect of adriamycin on Kruppel-like factor4 (Klf4), an essential pluripotent
      factor by choosing zebrafish embryos as a model system. Klf4 is involved in the
      regulation of cellular growth, proliferation, and differentiation. In zebrafish
      embryogenesis, Klf4 is a major regulator of differentiation of polster in the
      anterior mesendoderm region of cells into hatching gland cells. The importance of
      this study is to check the effect of adriamycin on embryonic development. We
      found, adriamycin dose dependently altered the gene expression level of Klf4 that
      occurs in parallel to its detrimental effect on hatching. Supportively, cathepsin
      L and cyclase-associated protein1 are the other two markers of hatching that are
      altered along with Klf4.

PMID- 30286260
TI  - Subunit Mass Analysis for Monitoring Multiple Attributes of Monoclonal
      Antibodies.
AB  - RATIONALE: Multi-Attribute Methods (MAMs) are appealing due to their ability to
      provide data on multiple molecular attributes from a single assay. If fully
      realized, such tests could reduce the number of assays required to support a
      product control strategy while providing equivalent or greater product
      understanding relative to the conventional approach. In doing so, MAMs have the
      potential to decrease development and manufacturing costs by reducing the number
      of tests in a release panel. METHODS: In this work, we report a MAM which is
      based on subunit mass analysis. RESULTS: The MAM assay is shown to be suitable
      for use as a combined method for identity testing, glycan profiling, and protein
      ratio determination for co-formulated monoclonal antibody (mAb) drugs. This is
      achieved by taking advantage of the high mass accuracy and relative
      quantification capabilities of intact mass analysis using quadrupole time of
      flight mass spectrometry (Q-TOF). Protein identification is achieved by comparing
      the measured masses of light chain (LC) and heavy chain (HC) of mAbs against
      their theoretical values. Specificity is based on instrument mass accuracy.
      Glycan profiling and relative protein ratios are determined by the relative peak
      intensities of the protein HC glycoforms and LC respectively. Results for these
      relative quantifications agree well with those obtained by the conventional
      hydrophilic interaction liquid chromatography (HILIC) and reversed phase LC
      methods. CONCLUSIONS: The suitability of this MAM method for use in a quality
      control setting is demonstrated through assessment specificity for mAb identity,
      and accuracy, precision, linearity and robustness for glycan profiling and ratio
      determination. Results from this study indicate that MAM with subunit mass
      analysis has the potential to replace three conventional methods widely used for
      mAb release testing including identification assay, glycosylation profiling, and
      ratio determination for co-formulated mAbs.

PMID- 30286261
TI  - Translating prenatal oral health clinical standards into dental education:
      results and policy implications.
AB  - OBJECTIVES: To evaluate characteristics of pregnant women served through the
      University of North Carolina's (UNC) prenatal oral health program (pOHP) dental
      clinic and community healthcare pathways to inform efforts in promoting prenatal
      oral health policies. METHODS: The pOHP provides medical and dental students and
      practitioners with interprofessional experiences caring for pregnant women. A
      retrospective chart audit captured 314 pregnant women who made appointments over
      33 months. Descriptive statistics and bivariate comparisons were computed to
      assess factors associated with dental appointment attendance and treatment
      completion. RESULTS: There were 564 pregnant women, with mean age of 29 years and
      gestation of 25 weeks, referred to the pOHP dental clinic from UNC OB-GYN and 20
      community sites. Only 56% (N = 314) scheduled an appointment. Of the 314
      appointed women, 55% (N = 172) attended at least one appointment. The majority
      (87%) presented with acute and/or complex treatment needs. Medicaid status was
      positively associated with appointment attendance (P = 0.001). Less than half
      (42%) of the women completed treatment prior to delivery. Mean maternal age,
      gestational age, and weeks to estimated date of delivery (EDD) were not
      significantly associated with completed treatment. CONCLUSIONS: This study
      provides descriptive evidence of an academic, interprofessional program's ability
      to provide safety-net dental care to pregnant women in the state of North
      Carolina. Results underscore the need for dental services among pregnant women,
      signaling for promotion of prenatal oral health clinical standards and informing
      policy on the state and national levels to maximize dental coverage.

PMID- 30286262
TI  - The effects of partial amniotic carbon dioxide insufflation in an ovine model.
AB  - OBJECTIVE: We aim to assess the effect of partial amniotic carbon dioxide
      insufflation (PACI) at increasing pressures on fetal acid-base, fetal-placental
      perfusion, and fetal membrane morphology in an ovine model. METHOD: Pregnant ewes
      and fetuses were instrumented under isoflurane anesthesia at 105 days gestation
      (term 145 days) to monitor utero-placental blood flow, fetal and maternal blood
      pressure, heart rate, and blood gas status. One group (n = 6) was exposed to PACI
      (unheated dry CO2 ), involving 10 mm Hg stepwise increases in insufflation
      pressure (5 to 25 mm Hg), for 80 minutes followed by 20 minutes of desufflation.
      Un-insufflated controls (n = 5) were monitored for 100 minutes. At postmortem,
      fetal membranes were collected for histological analysis. RESULTS: PACI at 25 mm
      Hg caused severe fetal hypercapnia (PaCO2  = 143 +/- 5 vs 54 +/- 5 mm Hg, P <
      0.001), acidosis (pH = 6.85 +/- 0.02 vs 7.25 +/- 0.02, P < 0.001), hypoxia (SaO2 
      = 31 +/- 4% vs 57 +/- 4%, P = 0.01), and reduced uterine artery flow (50 +/- 15
      vs 196 +/- 13 mL/min/kg, P = 0.005) compared with controls. These effects were
      greater at higher PACI pressures. PACI resulted in leukocyte infiltration in the
      amnion (1.77 * 10-5  +/- 0.61 * 10-5 vs 0.38 * 10-5  +/- 0.19 * 10-5  cells/MUm2
      , P = 0.04) and chorionic membranes (2.94 * 10-5  +/- 0.67 * 10-5 vs 0.84 * 10-5 
      +/- 0.42 * 10-5  cells/MUm2 , P = 0.01). CONCLUSION: Higher PACI pressures
      results in larger disturbances in fetal acid-base, uterine blood flow, and fetal
      membrane inflammation in sheep. Differences between human and sheep utero
      placental structure should be considered.

PMID- 30286263
TI  - Body mass index and sexual function in women with gynaecological cancer.
AB  - OBJECTIVES: To investigate the association between body mass index (BMI) and
      sexual functioning in gynaecologic cancer patients. To determine the association
      between socio-economic deprivation and sexual functioning. METHODS: This is a
      prospective cohort study on women undergoing surgery for suspected or proven
      gynaecological cancer between September 2014 and February 2016 in the Royal
      Cornwall Hospital Trust. Patients were invited to participate by completing the
      Female Sexual Function Index (FSFI) at three time points: preoperative, 3 months
      postoperative, and 1 year postoperative. A semiparametric model of the FSFI score
      was used to establish the association between BMI and sexual functioning.
      RESULTS: A total of 257 patients were approached of which 166 patients were
      included. Fifty-two patients (33.8%) were overweight (BMI, 25-29.9 kg/m2 ), 44
      (28.6%) were obese (BMI, 30-39.9 kg/m2 ), and a further 20 (13.0%) morbidly obese
      (BMI >= 40 kg/m2 ). Overweight and obese women reported improved sexual
      functioning compared with normal-weight women in endometrial, ovarian, and vulvar
      cancers. Among cervical cancer, worse sexual functioning was seen in women with
      an increased BMI; however, this was not significant. Younger age was associated
      with improved sexual function, and sexual functioning was better postoperatively
      for all patients compared with preoperatively. There was no evidence of
      relationship between deprivation and sexual functioning in gynaecological cancer
      patients. CONCLUSION: Higher BMI is associated with improved sexual functioning
      in endometrial, ovarian, and vulvar cancer; however, this was not seen in
      cervical cancer patients. There is no evidence of correlation between deprivation
      and sexual functioning.

PMID- 30286264
TI  - miR-34 regulates reproduction by inhibiting the expression of MIH, CHH, EcR, and
      FAMeT genes in mud crab Scylla paramamosain.
AB  - Mud crab Scylla paramamosain is a commercially important species widely cultured
      in China. It is well known that the eyestalk regulates reproductive activities in
      crustaceans. In our previous research, we found that the miR-34 expression level
      in male eyestalk was significantly higher than that in females. Thus, we assumed
      that it may play an important role in regulating reproduction. In this study, we
      used bioinformatic tools to identify the target genes of miR-34 in eyestalk. Six
      reproduction-related genes with an intact 3'-untranslated region (UTR), including
      molt-inhibiting hormone (MIH), crustacean hyperglycemic hormone (CHH),
      vitellogenesis-inhibiting hormone, red pigment concentrating hormone, ecdysone
      receptor (EcR), and farnesoic acid methyltransferase (FAMeT) were identified.
      When the 3'-UTR plasmid vectors of the six genes were cotransfected with miR-34
      mimics into 293FT cells, respectively, the luciferase activities of four genes
      (MIH, CHH, EcR, and FAMeT) were significantly decreased compared with that in the
      control group; on the contrary, when the six plasmid vectors were cotransfected
      with the miR-34 inhibitor respectively, the luciferase activities of four genes
      (MIH, CHH, EcR, and FAMeT) were significantly higher than that in the control
      group. When agomiR-34 and antagomiR-34 were injected into the eyestalk
      respectively in vivo, the expression levels of the MIH, CHH, EcR, and FAMeT genes
      were detected by a quantitative real-time polymerase chain reaction. The results
      showed that agomiR-34 suppressed the expression of the four genes, whereas
      antagomiR-34 enhanced their expression. These experimental results confirmed our
      hypothesis that miR-34 may indirectly regulate reproduction via binding to the 3'
      UTRs of MIH, CHH, EcR, and FAMeT genes and suppressing their expression.

PMID- 30286265
TI  - Does a Conjugation Site Affect Transport of Vitamin B12 -Peptide Nucleic Acid
      Conjugates into Bacterial Cells?
AB  - Gram-negative bacteria develop specific systems for the uptake of scarce
      nutrients, including vitamin B12 . These uptake pathways may be utilized for the
      delivery of biologically relevant molecules into cells. Indeed, it was recently
      reported that vitamin B12 transported an antisense peptide nucleic acid (PNA)
      into Escherichia coli and Salmonella Typhimurium cells. The present studies
      indicate that the conjugation site of PNA to vitamin B12 has an impact on PNA
      transport into bacterial cells. Toward this end, a specifically designed PNA
      oligomer has been tethered at various positions of vitamin B12 (central Co, R5' 
      OH, c and e amide chains, meso position, and at the hydroxy group of cobinamide)
      by using known or newly developed methodologies and tested for the uptake of the
      synthesized conjugates by E. coli. Compounds in which the PNA oligonucleotide was
      anchored at the R5' -OH position were transported more efficiently than that of
      other compounds tethered at the peripheral positions around the corrin ring. Of
      importance is the fact that, contrary to mammalian organisms, E. coli also takes
      up cobinamide, which is an incomplete corrinoid. This selectivity opens up ways
      to fight bacterial infections.

PMID- 30286266
TI  - Anomalous Stoichiometry and Antiferromagnetic Ordering for the Extended
      Hydroxymanganese(II) cubes/hexacyanometalate-based.
AB  - The reaction of MnII(O2CMe)2 and NaCN or LiCN in water forms a light green
      insoluble material. Structural solution and Rietveld refinement of high
      resolution synchrotron powder diffraction data for this unprecedented,
      complicated compound of previously unknown composition revealed an alkali free
      ordered new structural motif with [MnII4(u3-OH)4]4+ cubes and octahedral
      [MnII(CN)6]4- ions interconnected in 3-D via MnII-N=C-MnII linkages. The
      composition is {[MnII(OH2)3][MnII(OH2)]3}(u3-OH)4][MnII(u-CN)2(CN)4]*H2O =
      [MnII4(u3-OH)4(OH2)6][MnII(u-CN)2(CN)4]*H2O, which is further simplified to
      [Mn4(OH)4][Mn(CN)6](OH2)7 (1). 1 has four high-spin (S = 5/2) MnII sites that are
      antiferromagnetically coupled within the cube and are antiferromagnetically
      coupled to six low-spin (S = 1/2) octahedral [MnII(CN)6]4- ions. Above 40 K the
      magnetic susceptibility, chi(T), can be fit the Curie-Weiss expression, chi ?(T -
      theta)-1, with theta = -13.4 K, indicative of significant antiferromagnetic
      coupling and 1 orders as an antiferromagnet at Tc = 7.8 K.

PMID- 30286267
TI  - Facilitators for maternity waiting home utilisation at Attat Hospital: a mixed
      methods study based on 45 years of experience.
AB  - OBJECTIVE: To describe facilitators for maternity waiting home (MWH) utilisation
      from the perspectives of MWH users and health staff. METHODS: Data collection
      took place over several time frames between March 2014 and January 2018 at Attat
      Hospital in Ethiopia, using a mixed-methods design. This included seven in-depth
      interviews with staff and users, three focus group discussions with 28 users and
      attendants, a structured questionnaire among 244 users, a 2-week observation
      period and review of annual facility reports. The MWH was built in 1973;
      consistent records were kept from 1987. Data analysis was done through content
      analysis, descriptive statistics and data triangulation. RESULTS: The MWH at
      Attat Hospital has become a well-established intervention for high-risk pregnant
      women (1987-2017: from 142 users of 777 total attended births [18.3%] to 571 of
      3693 [15.5%]; range 142-832 users). From 2008, utilisation stabilised at on
      average 662 women annually. Between 2014 and 2017, total attended births doubled
      following government promotion of facility births; MWH utilisation stayed
      approximately the same. Perceived high quality of care at the health facility was
      expressed by users to be an important reason for MWH utilisation (114 of 128 MWH
      users who had previous experience with maternity services at Attat Hospital rated
      overall services as good). A strong community public health programme and
      continuous provision of comprehensive emergency obstetric and neonatal care
      (EmONC) seemed to have contributed to realising community support for the MWH.
      The qualitative data also revealed that awareness of pregnancy-related
      complications and supportive husbands (203 of 244 supported the MWH stay
      financially) were key facilitators. Barriers to utilisation existed (no cooking
      utensils at the MWH [198/244]; attendant being away from work [190/244]), but
      users considered these necessary to overcome for the perceived benefit: a healthy
      mother and baby. CONCLUSIONS: Facilitators for MWH utilisation according to users
      and staff were perceived high-quality EmONC, integrated health services,
      awareness of pregnancy-related complications and the husband's support in
      overcoming barriers. If providing high-quality EmONC and integrating health
      services are prioritised, MWHs have the potential to become an accepted
      intervention in (rural) communities. Only then can MWHs improve access to EmONC.

PMID- 30286268
TI  - Epidemiology of human adenovirus infection in children hospitalized with lower
      respiratory tract infections in Hunan, China.
AB  - To investigate the current genotypes of circulating human adenovirus (HAdV)
      strains, we molecularly genotyped HAdV in the nasopharyngeal aspirates (NPAs) of
      patients with acute lower respiratory tract infections (ALRTIs) and attempted to
      determine their associations with clinical symptoms. A total of 4751 NPA samples
      were collected from 4751 patients admitted to Hunan Provincial People's Hospital
      from September 2007 to March 2014, of which 447 (9.4%) samples were HAdV
      positive. Fourteen different HAdV types were identified; HAdV types 1 to 7 (HAdV
      1-7) were identified in 95.7% of the 447 NPA samples with HAdV-7 and HAdV-3 being
      the most prevalent. In addition, 93.3% (417 of 447) of patients were younger than
      5 years. The incidence of HAdV infection peaked in summer. Different HAdV types
      showed a predilection for different age groups and different seasonal
      distribution patterns. Coinfection of HAdVs and other respiratory viruses was
      detected in 63.3% (283 of 447) of the HAdV-positive samples. The most common
      clinical diagnosis was pneumonia and the most common symptoms were fever and
      cough. In comparison with children infected with HAdV-3 alone, those infected
      with HAdV-7 alone had an increased frequency of severe pneumonia involvement
      (11.6% vs 32.4%; P = 0.031), higher intensive care unit admission rates (7.0% vs
      26.5%; P = 0.019), and a longer length of hospital stay (P = 0.03). Mixed
      infections in younger children were associated with a longer hospital stay (P =
      0.023). Our results demonstrate the recent changes in the trends of circulating
      HAdV genotypes associated with ALRTIs in Hunan China.

PMID- 30286269
TI  - Lipid organization in xerosis: the key of the problem?
AB  - OBJECTIVE: Although xerosis is a common skin disorder among the population, there
      is no in vivo global study focusing on xerotic skin. Hence, the objective of this
      study was to characterize xerotic skin from the surface to the molecular scale
      with in vivo and non-invasive approaches. METHODS: For this purpose, 15 healthy
      volunteers with normal skin and 19 healthy volunteers with xerotic skin were
      selected by a dermatologist, thanks to a visual scorage. Firstly, the skin
      surface was characterized with biometric measurements. Then, the state of skin
      dryness was assessed by in vivo confocal microscopy. The molecular signature of
      xerotic skin was then determined by in vivo confocal Raman microspectroscopy.
      Finally, an identification of stratum corneum (SC) lipids was performed using
      Normal phase liquid chromatography (NP-LC) coupled to two detectors: Corona and
      High Resolution/Mass Spectroscopy (HR/MS). RESULTS: Results obtained at the skin
      surface displayed an increase in the transepidermal water loss (TEWL) and a
      decrease in the hydration rate in xerotic skin. Confocal microscopy revealed an
      alteration of the cell shape in xerotic skin. Moreover, confocal Raman
      microspectroscopy demonstrated directly in vivo and non-invasively the lack of
      organization and conformation of lipids in this skin. Finally, HPLC analyses
      revealed that the three ceramide sub-classes (NdS, NS and EOP) significantly
      decrease in xerosis. Altogether, these results identify parameters for the
      characterization of xerotic skin compared to normal. CONCLUSION: This study
      highlighted discriminative parameters from the surface to the molecular level in
      vivo and non-invasively between xerotic and normal skins. These results will be
      useful for the development of new cosmetic active ingredients dedicated to
      xerotic skin.

PMID- 30286270
TI  - Menstrual hygiene management and school absenteeism among adolescent students in
      Indonesia: evidence from a cross-sectional school-based survey.
AB  - OBJECTIVE: Assess prevalence of menstrual hygiene management (MHM) knowledge and
      practices among adolescent schoolgirls in Indonesia, and assess factors
      associated with poor MHM and school absenteeism due to menstruation. METHODS: A
      cross-sectional survey enrolled a representative sample of urban and rural school
      going girls aged 12-19 years in four provinces of Indonesia. A semi-structured,
      self-administered questionnaire obtained socio-demographic characteristics,
      knowledge, practices and attitudes related to menstruation, MHM, and school
      absenteeism. School water, sanitation and hygiene (WASH) facilities were also
      assessed. Univariate weighted population prevalence was estimated and
      multivariable logit regression analyses applied to explore associations. RESULTS:
      A total of 1,159 adolescent girls with a mean age of 15 years (sd=1.8)
      participated. Most girls (90.8%, 95% confidence interval (95%CI)=79.7-96.1) had
      reached menarche. Over half (64.1%, 95%CI=49.9-76.2) reported poor MHM practices,
      and 11.1% (95%CI=8.1-15.2) had missed one or more days of school during their
      most recent menstrual period. Poor MHM practices were associated with rural
      residence (AOR=1.73, 95%CI=1.13-2.64), province (various AOR), lower school grade
      (AOR=1.69, 95%CI=1.05-2.74), and low knowledge of menstruation (AOR=3.49,
      95%CI1.61-7.58). Absenteeism was associated with living in rural areas (AOR=3.96,
      95%CI=3.02-5.18), province (various AOR), higher school grade (AOR=3.02,
      95%CI=2.08-4.38), believing menstruation should be kept secret (AOR=1.47,
      95%CI=1.03-2.11), experiencing serious menstrual pain (AOR=1.68, 95%CI=1.06-2.68)
      and showed mixed associations with school WASH facilities. CONCLUSIONS: High
      prevalence of poor MHM and considerable school absenteeism due to menstruation
      among Indonesian girls highlight the need for improved interventions that reach
      girls at a young age and address knowledge, shame and secrecy, acceptability of
      WASH infrastructure and menstrual pain management. This article is protected by
      copyright. All rights reserved.

PMID- 30286271
TI  - Seroprevalence of sarcocystosis in the local communities of Pangkor and Tioman
      Islands using recombinant surface antigens 3 (rSAG3) of Sarcocystis falcatula.
AB  - OBJECTIVE: To investigate the seroprevalence of Sarcocystosis in the local
      communities of Pangkor and Tioman islands, Malaysia, by using antigenic
      recombinant surface antigens 2 and 3 from Sarcocystis falcatula (rSfSAG2 and
      rSfSAG3) as the target proteins via Western blot and ELISA assays. METHODS:
      SfSAG2 and SfSAG3 genes were isolated from S. falcatula and expressed in
      Escherichia coli expression system. A total of 348 serum samples [volunteers from
      both islands (n = 100), non-Sarcocystis parasitic infections patients (n = 50)
      and healthy donors (n = 100)] were collected and tested with purified SfSAGs in
      Western blot and ELISA assays to measure the seroprevalence of human
      sarcocystosis. RESULTS: None of the sera in this study reacted with rSfSAG2 by
      Western blot and ELISA. For rSfSAG3, relatively high prevalence of sarcocystosis
      was observed in Tioman Island (75.5%) than in Pangkor Island (34%) by Western
      blot. In ELISA, the different prevalence rate was observed between Tioman Island
      (43.8%) and Pangkor Island (37%). The prevalence rate in other parasitic
      infections (amoebiasis, cysticercosis, filariasis, malaria, toxocariasis and
      toxoplasmosis) was 30% by Western blot and 26% by ELISA. Only 8% (by Western
      blot) and 10% (by ELISA) of healthy donors showed reactivity towards rSfSAG3.
      CONCLUSION: This is the first study reporting a seroprevalence of sarcocystosis
      in Pangkor and Tioman Islands, Malaysia. The combination of Western blot and
      ELISA is suitable to be used for serodiagnosis of sarcocystosis. With further
      evaluations, SfSAG3 can potentially be used to confirm infection, asymptomatic
      screening, surveillance and epidemiological studies.

PMID- 30286273
TI  - Hollow Porous Heterometallic Phosphide Nanocubes for Enhanced Electrochemical
      Water Splitting.
AB  - Highly efficient earth-abundant electrocatalysts for both hydrogen evolution
      reaction (HER) and oxygen evolution reaction (OER) are of great importance for
      renewable energy conversion systems. Herein, hollow porous heterometallic
      phosphide nanocubes are developed as a highly active and robust catalyst for
      electrochemical water splitting via one-step phosphidation of a NiCoFe Prussian
      blue analogue. Through modulation of the composition of metals in the precursors,
      the optimal NiCoFeP exhibiting increased electrical conductivity and abundant
      electrochemically active sites, leading to high electrocatalytic activities and
      outstanding kinetics for both HER and OER, is successfully obtained. NiCoFeP
      shows low overpotentials of 273 mV for OER and 131 mV for HER at a current
      density of 10 mA cm-2 and quite low Tafel slopes of 35 mV dec-1 for OER and 56 mV
      dec-1 for HER.

PMID- 30286274
TI  - Beyond the Modification Degree: Impact of Raw Material on Physicochemical
      Properties of Gelatin Type A and Type B Methacryloyls.
AB  - Gelatin methacryloyl (acetyl) (GM(A)) is increasingly investigated for various
      applications in life sciences and medicine, for example, drug release or tissue
      engineering. Gelatin type A and type B are utilized for GA M(A) and GB M(A)
      preparation, but the impact of gelatin raw material on modification reaction and
      resulting polymer properties is rather unknown so far. Therefore, the degrees of
      modification (DMA) and physicochemical properties of five GA M(A) and GB M(A)
      derivatives are compared: The degrees of methacryloylation (0.32-0.98 mmol g-1 )
      are indistinguishable for GA M(A) and GB M(A) as are the sol-gel temperatures.
      Isoelectric points, solution viscosities, and hydrodynamic radii which are
      distinct for GA and GB, converge with increasing DMA. Interestingly, differences
      are measured for the storage moduli and equilibrium degrees of swelling of
      respective GA and GB derivative-based hydrogels, in spite of their comparable
      DMA. This underlines the importance of GM(A) characterization beyond the
      modification degree.

PMID- 30286275
TI  - Emergence of New Density-Strength Scaling Law in 3D Hollow Ceramic
      Nanoarchitectures.
AB  - Density-strength tradeoff appears to be an inherent limitation for most materials
      and therefore design of cell topology that mitigates strength decrease with
      density reduction has been a long-lasting engineering pursue for porous
      materials. Continuum-mechanics-based analyses of mechanical responses of
      conventional porous materials with bending-dominated structures often give the
      density-strength scaling law following the power-law relationship with an
      exponent of 1.5 or higher, which consequentially determines the upper bound of
      the specific strength for a material to reach. In this work, a new design
      criterion capable of significantly abating strength degradation in lightweight
      materials is presented, by successfully combining the size-induced strengthening
      effect in nanomaterials with the architectural design of cellular porous
      materials. Hollow-tube-based 3D ceramic nanoarchitectures satisfying such
      criterion are fabricated in large area using proximity field nano-patterning and
      atomic layer deposition. Experimental data from micropillar compression confirm
      that the strengths of these nanoarchitectural materials scale with relative
      densities with a power-law exponent of 0.93, a hardly observable value in
      conventional bending-dominated porous materials. This discovery of a new density
      strength scaling law in nanoarchitectured materials will contribute to creating
      new lightweight structural materials attaining unprecedented specific strengths
      overcoming the conventional limit.

PMID- 30286276
TI  - Microfluidic electrochemical immunosensor for the trace analysis of cocaine in
      water and body fluids.
AB  - Quick but accurate testing and on-the-spot monitoring of cocaine in oral fluids
      and urine continues to be an important toxicological issue. In terms of drug
      testing, a number of devices have been introduced into the market in recent
      decades, notably for workplace inspection or roadside testing. However, these
      systems do not always fulfill the requirements in terms of reliability,
      especially when low cut-off levels are required. With respect to surface water,
      the presence of anthropogenic small organic molecules such as prescription and
      over-the-counter pharmaceuticals as well as illicit drugs like cannabinoids,
      heroin, or cocaine, has become a challenge for scientists to develop new
      analytical tools for screening and on-site analysis because many of them serve as
      markers for anthropogenic input and consumer behavior. Here, a modular approach
      for the detection of cocaine is presented, integrating an electrochemical enzyme
      linked immunosorbent assay (ELISA) performed on antibody-grafted magnetic beads
      in a hybrid microfluidic sensor utilizing flexible tubing, static chip and screen
      printed electrode (SPE) elements for incubation, recognition, and cyclic
      voltammetry measurements. A linear response of the sensor vs. the logarithm of
      cocaine concentration was obtained with a limit of detection of 0.15 ng/L. Within
      an overall assay time of 25 minutes, concentrations down to 1 ng/L could be
      reliably determined in water, oral fluids, and urine, the system possessing a
      dynamic working range up to 1 mg/L.

PMID- 30286277
TI  - Automated Scalpel Patterning of Solution Processed Thin Films for Fabrication of
      Transparent MXene Microsupercapacitors.
AB  - A simple and generic strategy is proposed to pattern thin films deposited by a
      solution processable route. A soft approach based on an automated scalpel
      technique is developed to engrave thin films in a single step for sculpting
      functional planar devices. MXenes-the emerging family of 2D transition metal
      carbides and nitrides-combine metallic conductivity and hydrophilicity, enabling
      solution processing of transparent conducting electrodes (TCEs) under ambient
      conditions. Scalable dip coating is employed to process titanium carbide, Ti3 C2
      , MXene thin films with excellent optoelectronic properties, achieving electrical
      Figure of merit up to 14. Automated scalpel engraving is adopted to fabricate
      transparent and semi-transparent MXene microsupercapacitors in a single step,
      hitherto not reported. Combining TCE and pseudocapacitive characteristics, MXene
      devices show excellent capacitive storage capabilities at high rates, without the
      aid of external metal current collectors. This technique allows for maskless
      patterning of solution processed thin films without losing intrinsic
      physicochemical properties and can be extended to fabricate heterostructured
      hybrid devices out of solution processable materials.

PMID- 30286278
TI  - Effect of recipient gender and donor-specific antibodies on antibody-mediated
      rejection after heart transplantation.
AB  - Gender-difference regarding antibody-mediated rejection (AMR) after heart
      transplantation has been described. However, no study accounted for the presence
      of preformed donor-specific antibodies (pfDSA), a known risk factor of AMR, more
      common among women than men. In a single-institution 6-year cohort (2010-2015),
      time to AMR was assessed, comparing men with women by survival analysis with a 1
      year death-censored follow-up. All AMRs were biopsy proven. Confounding variables
      that were accounted for included mean intensity fluorescence (MFI) of pfDSA,
      recipient age, HLA-, size- and sex-mismatch. 463 patients were included. Overall
      incidence of AMR was 10.3% at 1 year. After adjusting for confounding variables,
      independent risk factors of AMR were female recipient gender (adjusted hazard
      ratio [adj. HR] = 1.78 [1.06-2.99]), P = .03) and the presence of pfDSA (adj. HR
      = 3.20 [1.80-5.70], P < .001). This association remained significant when
      considering pfDSA by their MFI; female recipient gender had an adj. HR = 2.2 (P =
      .026) and MFI of pfDSA (per 1 MFI-increase) adj. HR = 1.0002 (P < .0001). In this
      cohort, women were at higher risk of AMR than men and this risk increase was
      additive to that of pfDSA. These findings may suggest a gender-related difference
      in the severity of pfDSA.

PMID- 30286279
TI  - Zinc-Incorporated Microporous Molecular Sieve for Mild Catalytic Hydrolysis of
      gamma-Valerolactone: A New Selective Route for Biomass Conversion.
AB  - gamma-Valerolactone (GVL) is regarded as a key platform molecule in the
      production of fine chemicals such as pentenoic acid (PA) from biomass. Although
      PA is believed to be the key intermediate in solid-acid-catalyzed reactions of
      GVL, due to subsequent facile decarboxylation reactions further alkene products
      are formed. Here, by tailoring the acidity of Bronsted acid sites in an
      aluminophosphate (AlPO) molecular sieve through incorporation of Zn2+ into the
      framework, we access a new selective and effective catalyst for GVL conversion to
      PA.

PMID- 30286281
TI  - Carbon-Dot-Based Heterojunction for Engineering Band-Edge Position and
      Photocatalytic Performance.
AB  - A photocatalytic reaction is always governed by energy band configuration of the
      catalyst, but its modulation is challenging. Here, the adjustment of band-edge
      positions of Ag3 PO4 through fluorescent carbon dots is reported for the first
      time. Both Ag3 PO4 and carbon dots which keep the similar sizes constitute a
      heterojunction. Such heterostructure not only promotes visible light absorption,
      photogenerated charge separation, and transfer, but it also transforms
      photocatalytic activity of Ag3 PO4 from photooxidation to photoreduction due to
      the huge changes of band-edge positions. In addition, the heterojunction
      structure of carbon dots and Ag3 PO4 exhibits unique temperature-responsive
      photocatalytic activities and higher photocatalytic stability than the pure Ag3
      PO4 . According to the contrast experiments and related characterizations, the
      possible mechanism of photocatalytic reaction is proposed. Therefore, this work
      offers an alternative route for adjusting energy band positions or tuning
      photocatalytic performance as well as for preparing novel carbon-dot-based
      heterostructure.

PMID- 30286280
TI  - Radiofrequency-Triggered Drug Release from Nanoliposomes with Millimeter-Scale
      Resolution Using a Superimposed Static Gating Field.
AB  - Drug delivery to a specific site in the body typically relies on the use of
      targeting agents that recognize a unique biomarker. Unfortunately, it is often
      difficult to identify unique molecular signatures that exist only at the site of
      interest. An alternative strategy is to deliver energy (e.g., light) to locally
      trigger release from a drug carrier; however, the use of this approach is limited
      because energy delivery to deep tissues is often impractical or invasive. In this
      work, radiofrequency-responsive superparamagnetic iron oxide nanoparticles
      (SPIONs) are used to trigger drug release from nanoscale vesicles. Because the
      body is inherently nonmagnetic, this approach allows for deep tissue targeting.
      To overcome the unfavorable meter-scale diffraction limit of SPION-compatible
      radiofrequency (RF) fields, a strong static gating field containing a sharp zero
      point is superimposed on the RF field. Only drug carriers that are at or near the
      zero point are susceptible to RF-triggered drug release, thereby localizing drug
      delivery with millimeter-scale resolution. This approach induces >40% drug
      release from thermally responsive doxorubicin-loaded liposomes within a 3.2 mm
      radius of the zero point with <10% release in the surrounding area, leading to a
      >2.5 therapeutic index in Huh 7 hepatocellular carcinoma cells.

PMID- 30286282
TI  - Nucleus of Circulating Tumor Cell Determines Its Translocation Through Biomimetic
      Microconstrictions and Its Physical Enrichment by Microfiltration.
AB  - The mechanism of cells passing through microconstrictions, such as capillaries
      and endothelial junctions, influences metastasis of circulating tumor cells
      (CTCs) in vivo, as well as size-based enrichment of CTCs in vitro. However, very
      few studies observe such translocation of microconstrictions in real time, and
      thus the inherent biophysical mechanism is poorly understood. In this study, a
      multiplexed microfluidic device is fabricated for real-time tracking of cell
      translocation under physiological pressure and recording deformation of the whole
      cell and nucleus, respectively. It is found that the deformability and size of
      the nucleus instead of the whole cell dominate cellular translocation through
      microconstrictions under a normal physiological pressure range. More
      specifically, cells with a large and stiff nucleus are prone to be blocked by
      relatively small constrictions. The same phenomenon is also observed in the size
      based enrichment of CTCs from peripheral blood of metastatic cancer patients.
      These findings are different from a popular viewpoint that the size and
      deformability of a whole cell mainly determine cell translation through
      microconstrictions, and thus may elucidate interactions between CTCs and
      capillaries from a new perspective and guide the rational design of size-based
      microfilters for rare cell enrichment.

PMID- 30286283
TI  - Nitride-Based Microlight-Emitting Diodes Using AlN Thin-Film Electrodes with
      Nanoscale Indium/Tin Conducting Filaments.
AB  - Microlight-emitting diodes (uLEDs) are emerging solutions for both high-quality
      displays and lighting technologies. However, the overall light output power
      density of these devices is low, as the emission area is shielded by the p
      electrodes required for current injection. In this study, instead of the more
      conventionally used indium tin oxide (ITO), an AlN thin film with nanoscale
      conducing filaments (CFs) is used, referred to as CF-AlN, as a transparent
      conducting electrode (TCE), to enhance the output power density from the same
      emission area. As a result of this modification, the electroluminescence
      intensity is enhanced by 10% at an injection current of 10 mA, and the current
      density is improved by 13% at a forward voltage of 4.9 V, in comparison to the
      parameters observed with ITO-based uLEDs. This improvement is attributed to the
      higher transmittance of CF-AlN TCEs, together with efficient hole injection from
      the p-electrode into the light-emitting layer, through the CFs formed in the AlN
      layer. In addition, using transmission electron microscopy analyses, the origin
      of the CFs is directly identified as the diffusion of In and Sn ions, which
      provides critical insight into the conduction mechanism of AlN-based TCEs.

PMID- 30286284
TI  - Simultaneous Determination of Uranium and Depleted Uranium Isotopic Ratio Using
      Inductively Coupled Mass Spectrometry.
AB  - We have developed and validated a method for the simultaneous quantitative
      measurement of total uranium (TU) and uranium 235 U/238 U isotopic ratio (UIR) in
      urine by inductively coupled plasma mass spectrometry (ICP-MS) using a Thermo
      Scientific iCAP-Q instrument. The performance characteristics of the assay were
      determined to be in compliance with clinical laboratory standards. The assay was
      linear in the concentration range of 1.0 to 500.0 ng/liter TU. The method was
      precise and accurate with limits of detection of 2.5 ng/liter for TU and 9.8
      ng/liter for UIR. The accuracy was >93% and the coefficient of variation (% CV)
      was <5.0% for both TU and UIR. All results were within established guidelines and
      agreed-upon criteria, and the results fell within the certified range for the
      reference controls. The method has thus been shown to be effective as a simple,
      precise, and sensitive analytical technique for testing urine samples. (c) 2018
      by John Wiley & Sons, Inc.

PMID- 30286285
TI  - Surfactant-Stripped Micelles of Near Infrared Dye and Paclitaxel for
      Photoacoustic Imaging Guided Photothermal-Chemotherapy.
AB  - Development of nanoagents with strong near-infrared (NIR) absorbance and high
      photothermal conversion capacity is highly desired for efficient photoacoustic
      (PA) imaging and photothermal therapy of cancers. Herein, surfactant-stripped
      micelles with photostable near-infrared dye, beta-thiophene-fused BF2 
      azadipyrromethene (aza-BDTP), are prepared in the presence of paclitaxel (PTX)
      with Pluronic F127 as the surfactant. Distinct from hydrophobic aza-BDTP and PTX,
      the obtained surfactant-stripped micelles aza-BDTP/PTX show excellent solubility,
      physiological stability, and high loading efficiencies for corresponding aza-BDTP
      and PTX. Intriguingly, these aza-BDTP/PTX micelles exhibit high photothermal
      conversion efficiency at 33.9%, significantly higher than 16.9% for bare aza-BDTP
      molecules, owing to aggregation-induced quenching of aza-BDTP fluorescence. With
      excellent photostability, aza-BDTP/PTX micelles appear to be a highly stable
      photoacoustic imaging probe and show efficient tumor accumulation as visualized
      under photoacoustic imaging upon intravenous injection. After being irradiated
      with a 785 nm laser, 4T1 tumors on the mice with systemic administration of aza
      BDTP/PTX micelles are fully eradiated without any recurrences within 60 d. This
      work presents a general method for efficient encapsulation of hydrophobic aza
      BDTP and PTX, obtaining hybrid aza-BDTP/PTX micelles as promising
      nanotheranostics for imaging guided cancer combination therapy.

PMID- 30286286
TI  - Emergence of letermovir resistance in a lung transplant recipient with
      ganciclovir-resistant cytomegalovirus infection.
AB  - Following a year of valganciclovir prophylaxis, a lung transplant recipient
      developed cytomegalovirus (CMV) infection that became resistant to ganciclovir,
      as confirmed by detection of UL97 kinase mutation M460V and a previously
      uncharacterized UL54 DNA polymerase mutation L516P. The latter mutation is now
      shown to confer ganciclovir and cidofovir resistance. As predicted from the viral
      genotype, foscarnet therapy was effective, but resumption of valganciclovir as
      secondary prophylaxis resulted in a plasma viral load rebound to 3.6 log10
      copies/mL several weeks later. Valganciclovir was then replaced by letermovir,
      resulting in gradual viral load reduction in the first 5 weeks to below the
      quantitation limit (2.7 log10 copies/mL) for 1 week, followed by 10 weeks of
      rising viral loads reaching 4.3 log10 copies/mL while on letermovir. At this
      point, CMV genotypic testing revealed UL56 mutation C325Y, which confers absolute
      resistance to letermovir. Retreatment with foscarnet was successful. This case
      adds to the considerable list of proven ganciclovir resistance mutations, and
      provides an early experience with letermovir resistance after off-label
      therapeutic use. This experience is consistent with in vitro observations of
      rapid emergence of letermovir-resistant CMV after drug exposure.

PMID- 30286287
TI  - A-Crater-within-a-Crater Approach for Secondary Ion Mass Spectrometry Evaluation
      of the Quality of Interfaces of Multilayer Devices.
AB  - Further development and optimization of modern optoelectronic devices requires
      fast and reliable procedures that may evaluate the quality of interfaces. For
      thick multilayer devices, mixing effect may significantly prevent proper
      interpretation of secondary ion mass spectrometry depth profiles especially if a
      region of interest is located far from the sample surface. In this work, we
      present how to overcome this problem with a so-called a-crater-within-a-crater
      approach. In this notion, a high energetic primary ion beam is used to rapidly
      remove most of the material forming a large crater. Then, the energy is
      significantly reduced and a new smaller crater is formed at the bottom of the
      previous one. Close to the region of interest, the impact energy is decreased to
      150 eV and thus an interface can be analyzed with minimal mixing effect and thus
      its quality can be adequately assessed. Usefulness of this approach is tested on
      an epitaxial structure of a triple-junction solar cell and reliable information
      about the structure imperfection has been obtained: p and n dopants in the tunnel
      junction overlapped, deteriorating the operation of the device.

PMID- 30286288
TI  - Amorphous Europium Hexaboride: A Potential Room Temperature Formaldehyde Sensing
      Material.
AB  - Amorphous EuB6 was successfully prepared having a high specific surface area
      (221.3 m2 g-1) via the reaction between EuCl3 and B2H6 in the presence of liquid
      plasma in an ionic liquid environment. The material exhibits an immediate,
      lasting, and highly selective response toward formaldehyde at room temperature
      with a detection limit of 50 ppb. The good sensing performance of the amorphous
      EuB6 material is attributed to the strong interaction between formaldehyde and
      the increased number of accessible electron-rich surface Eu sites.

PMID- 30286289
TI  - Isotropic Atomic Layer Etching of ZnO Using Acetylacetone and O2 Plasma.
AB  - Atomic layer etching (ALE) provides Angstrom-level control over material removal
      and holds potential for addressing the challenges in nanomanufacturing faced by
      conventional etching techniques. Recent research has led to the development of
      two main classes of ALE: ion-driven plasma processes yielding anisotropic (or
      directional) etch profiles and thermally driven processes for isotropic material
      removal. In this work, we extend the possibilities to obtain isotropic etching by
      introducing a plasma-based ALE process for ZnO which is radical-driven and
      utilizes acetylacetone (Hacac) and O2 plasma as reactants. In situ spectroscopic
      ellipsometry measurements indicate self-limiting half-reactions with etch rates
      ranging from 0.5 to 1.3 A/cycle at temperatures between 100 and 250  degrees C.
      The ALE process was demonstrated on planar and three-dimensional substrates
      consisting of a regular array of semiconductor nanowires (NWs) conformally
      covered using atomic layer deposition of ZnO. Transmission electron microscopy
      studies conducted on the ZnO-covered NWs before and after ALE proved the
      isotropic nature and the damage-free characteristics of the process. In situ
      infrared spectroscopy measurements were used to elucidate the self-limiting
      nature of the ALE half-reactions and the reaction mechanism. During the Hacac
      etching reaction that is assumed to produce Zn(acac)2, carbonaceous species
      adsorbed on the ZnO surface are suggested as the cause of the self-limiting
      behavior. The subsequent O2 plasma step resets the surface for the next ALE
      cycle. High etch selectivities (~80:1) over SiO2 and HfO2 were demonstrated.
      Preliminary results indicate that the etching process can be extended to other
      oxides such as Al2O3.

PMID- 30286290
TI  - Zinc-Supported Multiwalled Carbon Nanotube Nanocomposite: A Synergism to
      Micronutrient Release and a Smart Distributor To Promote the Growth of Onion
      Seeds in Arid Conditions.
AB  - In the current scenario, nanotechnological applications in the agriculture sector
      showing potential impacts on the improvement of plant growth in terms of
      protection and safety are at a very nascent stage. The present study deals with
      the synergistic role of zinc (Zn) and multiwalled carbon nanotubes (MWCNTs)
      synthesized as a zinc oxide (ZnO)/MWCNT nanocomposite, a prospective applicant to
      modulate the micronutrient supply and enhance the growth of onion seeds, thereby
      replacing harmful, unsafe chemical fertilizers. To the best of our knowledge,
      this is the first report wherein MWCNTs have been envisaged as a micronutrient
      distributor and a nutrient stabilizer enhancing the growth of onion plant under
      arid conditions. The growth trend of onion seeds was evaluated in an aqueous
      medium with varied concentrations of (i) MWCNTs, (ii) zinc oxide nanoparticles,
      and (iii) ZnO/MWCNT nanocomposites. ZnO/MWCNT nanocomposites with 15 MUg/mL
      concentration displayed the best seedling growth with the maximum number of cells
      in telophase. A significant growth trend with increased concentration of
      ZnO/MWCNTs displayed no negative impact on plant growth in contrast to that with
      the use of MWCNTs. The synergistic impact of Zn nanoparticles and MWCNTs in
      ZnO/MWCNT nanocomposites on the rate of germination was explained via a mechanism
      supported by scanning transmission electron microscopy.

PMID- 30286291
TI  - Rapid Determination of Procyanidins Using MALDI-ToF/ToF Mass Spectrometry.
AB  - Although procyanidins constitute a unique class of polymeric plant secondary
      metabolites with a variety of biological properties including potent antioxidant
      activity, structure determination has been challenging, and structures of many
      complex procyanidins remain uncertain. To expedite the characterization of
      procyanidins, negative ion matrix-assisted laser desorption ionization high
      energy collision-induced dissociation tandem time-of-flight (MALDI-ToF/ToF) mass
      spectra of 20 isolated procyanidins containing catechin and epicatechin subunits
      with degrees of polymerization up to five were obtained and evaluated.
      Structurally significant fragmentation pathways of singly charged, deprotonated
      molecules were identified representing quinone methide, heterocyclic ring
      fission, and retro-Diels-Alder fragmentation. The interpretation of the tandem
      mass spectra for sequencing A-type, B-type, mixed-type, linear, and branched
      procyanidins is explained using specific examples of each.

PMID- 30286292
TI  - Discovery of RG7834: The First-in-Class Selective and Orally Available Small
      Molecule Hepatitis B Virus Expression Inhibitor with Novel Mechanism of Action.
AB  - Chronic hepatitis B virus (HBV) infection is a serious public health burden and
      current therapies cannot achieve satisfactory cure rate. There are high unmet
      medical needs of novel therapeutic agents with differentiated mechanism of action
      (MOA) from the current standard of care. RG7834, a compound from the
      dihydroquinolizinone (DHQ) chemical series, is a first-in-class highly selective
      and orally bioavailable HBV inhibitor which can reduce both viral antigens and
      viral DNA with a novel mechanism of action. Here we report the discovery of
      RG7834 from a phenotypic screening and the structure-activity relationship (SAR)
      of the DHQ chemical series. RG7834 can selectively inhibit HBV but not other DNA
      or RNA viruses in a virus panel screening. Both in vitro and in vivo profiles of
      RG7834 are described herein, and the data support further development of this
      compound as a chronic HBV therapy.

PMID- 30286293
TI  - Characterization of an Unusual Glycerate Esterification Process in Vioprolide
      Biosynthesis.
AB  - Bacteria produce a large number of secondary metabolites with extraordinary
      chemical structures and bioactivities. Vioprolides are promising anticancer and
      antifungal lead compounds produced by the myxobacterium Cystobacter violaceus Cb
      vi35, which are initially synthesized as acylated precursors (previoprolides) by
      nonribosomal peptide synthetases (NRPS). Here, we describe and characterize an
      unprecedented glycerate esterification process in the biosynthesis of
      vioprolides. In vitro biochemical investigations revealed that the fatty acyl
      chain of previoprolides is adenylated by the starting fatty acyl-AMP ligase
      (FAAL) domain, while the glycerate moiety is incorporated by the FkbH domain. An
      unusual ester-bond forming condensation domain is shown responsible for the
      acylation of glycerate. LC-MS analysis and bioactivity assays suggest that the
      acylation serves for directed membrane transport rather than representing a
      prodrug mechanism.

PMID- 30286294
TI  - Morphological Transitions of Water Channels Induced by Vertical Vibrations.
AB  - We report the results of comprehensive experiments and numerical calculations of
      interfacial morphologies of water confined to the hydrophilic top face of
      rectangular posts subjected to vertical vibrations. In response to mechanical
      driving, an initially flat liquid channel is collected into a liquid bulge that
      forms in the center of the rectangular post if the acceleration exceeds a certain
      threshold. The bulge morphology persists after the driving is switched off, in
      agreement with the morphological bistability of static interfacial shapes on
      posts with large length-to-width ratios. In a narrow frequency band, the channel
      does not decay into a bulge at any acceleration amplitude, but displays irregular
      capillary waves and sloshing instead. On short posts, however, a liquid bulge can
      be dynamically sustained through vertical vibrations but quickly decays into a
      homogeneous channel after the external driving is stopped. To explain the dynamic
      bulging of the liquid interface, we propose an effective lifting force pulling on
      the drop's slowly moving center of mass in the presence of fast oscillation
      modes.

PMID- 30286295
TI  - Confined Structures and Selective Mass Transport of Organic Liquids in Graphene
      Nanochannels.
AB  - Selective transport of liquids is an important process in the energy and
      environment industry. The increased energy consumption and the demands of clean
      water and fossil fuels have urged the development of high-performance membrane
      technologies. Nanoscale channels with the critical size for molecular sieving and
      atomistically smooth walls for significant boundary slippage are highly promising
      to balance the tradeoff between permeability and selectivity. In this work, we
      explore the molecular structures and dynamics of organic solvents and water,
      which are confined within nanoscale two-dimensional galleries between graphene or
      graphene oxide sheets. Molecular dynamics simulation results show that the
      layered order and significant interfacial slippage are universal for all
      molecular liquids, leading to notable flow enhancement for channels with a width
      of few nanometers, in the order of ethylene glycol > butanol > ethanol > hexane >
      toluene > water > acetone. The extracted dependence of permeability, selectivity
      on the channel width, and properties of molecular liquids clarify the underlying
      mechanisms of selective mass transport in nanofluidics, which help to understand
      and control the filtration and separation processes of molecular liquids. The
      performance of graphene oxide membranes for permeation and filtration is finally
      discussed based on the calculated flow resistance for pressure-driven flow or
      molecular diffusivity for diffusive flow, as well as the solubility and
      wettability of membranes.

PMID- 30286296
TI  - Human iPS Cell-Derived Patient Tissues and 3D Cell Culture Part 1: Target
      Identification and Lead Optimization.
AB  - Human-induced pluripotent stem cells (HiPSCs), and new technologies to culture
      them into functional cell types and tissues, are now aiding drug discovery.
      Patient-derived HiPSCs can provide disease models that are more clinically
      relevant and so more predictive than the currently available animal-derived or
      tumor cell-derived cells. These cells, consequently, exhibit disease phenotypes
      close to the human pathology, particularly when cultured under conditions that
      allow them to recapitulate the tissue architecture in three-dimensional (3D)
      systems. A key feature of HiPSCs is that they can be cultured under conditions
      that favor formation of multicellular spheroids or organoids. By culturing and
      differentiating in systems mimicking the human tissue in vivo, the HiPSC
      microenvironment further reflects patient in vivo physiology, pathophysiology,
      and ultimately pharmacological responsiveness. We assess the rationale for using
      HiPSCs in several phases of preclinical drug discovery, specifically in disease
      modeling, target identification, and lead optimization. We also discuss the
      growing use of HiPSCs in compound lead optimization, particularly in profiling
      compounds for their potential metabolic liability and off-target toxicities.
      Collectively, we contend that both approaches, HiPSCs and 3D cell culture, when
      used in concert, have exciting potential for the development of novel medicines.

PMID- 30286297
TI  - DIRECT INHIBITORY EFFECT OF FLAXSEED ON PORCINE OVARIAN GRANULOSA CELL FUNCTIONS.
AB  - Flaxseed is useful as a functional food and alternative medicine owing to its
      beneficial health effects. Its action on ovarian cell functions and
      interrelationships with the upstream hormonal regulators remain unknown. Our aim
      was to examine the direct influence of flaxseed extract on basal porcine ovarian
      functions (proliferation, apoptosis), leptin release, and response to insulin
      like growth factor I (IGF-I). First, we examined the effect of flaxseed extract
      on the accumulation of proliferation (PCNA) and apoptosis (bax) marker and on
      leptin release in cultured porcine ovarian granulosa cells. Next, granulosa cells
      were cultured with IGF-I with and without flaxseed extract and analyzed for PCNA
      and bax accumulation by quantitative immunocytochemistry, whereas leptin was
      analyzed by RIA. Flaxseeds decreased the accumulation of proliferation marker and
      increased that of the apoptosis marker at all doses and reduced leptin output at
      100 ug/ml. On the contrary, IGF-I promoted PCNA and suppressed bax. Flaxseed did
      not modify IGF-I action on these parameters. Thus, we showed flaxseed action on
      porcine reproductive processes, with a direct effect on the ovary and flaxseed
      ability to affect ovarian cell proliferation, apoptosis, and leptin release.
      Furthermore, we confirmed the pro-proliferating and anti-apoptosis action of IGF
      I, but indicated that flaxseed action on ovarian cell proliferation and apoptosis
      are not due to changes in their response to IGF-I. The potential direct anti
      reproductive action of flaxseed needs to be confirmed properly in in-vivo
      experiments and thereafter considered during its application in nutrition,
      medicine, and animal production.

PMID- 30286298
TI  - Military Deployments and Suicide: A Critical Examination.
AB  - Deployment to a combat zone is a fundamental mission for most military forces,
      but prior research suggests that there is a complex and nuanced association
      between deployment and related risk factors for suicide. Deployment and combat
      experiences vary greatly among military personnel and can affect a variety of
      protective and risk factors for suicide. This article offers a critical
      examination of the association among modern U.S. military deployments, suicide
      attempts, and death while considering the context of a prominent theory of
      suicide. Although previous work has demonstrated that deployment is not
      associated with suicide overall in this population, there is growing evidence
      that risk may be elevated shortly after deployment, and for some subgroups.
      Specific aspects of combat exposure, including the experience of killing or
      witnessing death in combat, may be important contributing factors. An analysis of
      the literature illustrates that deployment-related risk factors for suicide are
      complex. The limitations of the literature are discussed, and future directions
      are suggested.

PMID- 30286300
TI  - Changes in exercise capacity and serum BDNF following long-term sprint interval
      training in well-trained cyclists.
AB  - The study determined the effects of sprint interval training on the acute and
      chronic changes of serum brain-derived neurotrophic factor (BDNF) and aerobic
      capacity. Twenty-six cyclists were divided into experimental (E) and control (C)
      group. Both groups executed 6-month exercise intervention involving high
      intensity interval training (HIIT) and continuous endurance training (CET) with
      group E replacing HIIT and CET sessions with sprint interval training (SIT)
      executed twice a week. Two exercise tests were administered prior to the
      intervention and 2 and 6 months after study outset. Incremental exercise test
      (IXT) assessed aerobic capacity by measuring maximal oxygen uptake (VO2max) and
      work output, and sprint interval exercise test (SIXT; three sets of four 30-s all
      out repetitions interspersed with 90 s of rest with sets separated by 25-40 min
      active recovery). Oxygen uptake, work output, BDNF and vascular endothelial
      growth factor A (VEGF-A) concentrations (baseline, 10 min after first set and 10
      and 60 min after third SIXT set), were taken during the sprint interval exercise
      test. Significant decreases in BDNF relative to baseline values were observed 10
      min after first set and 60 min after third set in group E at the 2- and 6-month
      assessments. Increases baseline VEGF-A after 2 and 6 months of training and
      increase VO2max after 2 months of training was also observed only in group E. The
      inclusion of SIT with HIIT and CET shows positive long-term effects including
      increased VO2max and baseline VEGF-A and reduction BDNF below baseline levels
      during and after SIXT.

PMID- 30286299
TI  - Blight Abatement of Vacant Land and Crime in New Orleans.
AB  - OBJECTIVES:: In 2005, Hurricane Katrina caused damage in New Orleans, Louisiana,
      and much of the land in low-resource neighborhoods became vacant and blighted. In
      2014, New Orleans launched a program, Fight the Blight, which remediated
      properties in 6 neighborhoods. Our objective was to examine changes in crime
      rates near lots that were remediated (ie, debris removed and vegetation mowed).
      METHODS:: We used a quasi-experimental design to test whether crime rates changed
      from preremediation (January 2013-October 2014) to postremediation (July 2016
      March 2017) near 204 vacant lots that were remediated compared with 560 control
      vacant lots that were not remediated between October 2014 and July 2016. We also
      examined differences between remediated lots that received 1 treatment (n = 64)
      and those that received >=2 treatments (n = 140). RESULTS:: We found no
      significant differences between remediated and control lots in levels of violent,
      property, and domestic crimes from preremediation to postremediation. However,
      the number of drug crimes per square mile decreased significantly near all
      remediated lots (5.7% lower; P < .001) compared with control lots, largely driven
      by the significant decrease (6.4% lower; P < .001) in drug crimes found near lots
      that received >=2 treatments. CONCLUSIONS:: Investing in programs that improve
      neighborhood environments affected by high rates of physical disorder and vacancy
      may be a way to decrease violence. However, routine remediation may be needed to
      increase the public health impact of blight abatement programs in warmer
      climates, where weeds and vegetation grow rapidly.

PMID- 30286301
TI  - Integrating a nationally scaled workforce of community health workers in primary
      care: a modelling study.
AB  - Objective To model cost and benefit of a national community health worker
      workforce. Design Modelling exercise based on all general practices in England.
      Setting United Kingdom National Health Service Primary Care. Participants Not
      applicable. Data sources Publicly available data on general practice
      demographics, population density, household size, salary scales and screening and
      immunisation uptake. Main outcome measures We estimated numbers of community
      health workers needed, anticipated workload and likely benefits to patients.
      Results Conservative modelling suggests that 110,585 community health workers
      would be needed to cover the general practice registered population in England,
      costing L2.22bn annually. Assuming community health workerss could engage with
      and successfully refer 20% of eligible unscreened or unimmunised individuals, an
      additional 753,592 cervical cancer screenings, 365,166 breast cancer screenings
      and 482,924 bowel cancer screenings could be expected within respective review
      periods. A total of 16,398 additional children annually could receive their MMR1
      at 12 months and 24,716 their MMR2 at five years of age. Community health
      workerss would also provide home-based health promotion and lifestyle support to
      patients with chronic disease. Conclusion A scaled community health worker
      workforce integrated into primary care may be a valuable policy alternative.
      Pilot studies are required to establish feasibility and impact in NHS primary
      care.

PMID- 30286302
TI  - Anthropometric measures associated with fat mass estimation in children and
      adolescents with HIV.
AB  - To verify the association between anthropometric indicators and body fat
      percentage (F %) estimated by dual X-ray absorptiometry (DXA) and air
      displacement plethysmography (ADP) in children and adolescents diagnosed with
      HIV. This cross-sectional study was carried out with 62 children and adolescents
      with HIV (8 to 15 years). F % was estimated by DXA and ADP. Anthropometric
      indicators were skinfolds (abdominal, triceps, subscapular, calf); perimeter
      relaxed arm (PRA), waist circumference (WC), perimeter neck (PN); body mass index
      (BMI); waist-to-height ratio (WHR); conicity index and body adiposity index.
      Linear regressions were performed with 5% significance level. In boys (R2adj =
      0.38 to R2adj = 0.67) and girls (R2adj = 0.41 to R2adj = 0.57), all
      anthropometric indicators were associated with F% estimated by DXA. For boys,
      skinfolds were associated with F % estimated by ADP (R2adj = 0.18 to R2adj =
      0.35). In girls, skinfolds (R2adj = 0.27 to R2adj = 0.44, BMI (R2adj = 0.31), PRA
      (R2adj = 0.36) and WC (R2adj = 0.26) were associated to F % by ADP. Abdominal
      skinfold was the indicator that most explained the variation in F % measured by
      DXA and ADP in both sexes. Anthropometric indicators are strongly associated with
      body fat, measured by reference methods, and can assist health professionals in
      monitoring the health of children and adolescents with HIV.

PMID- 30286303
TI  - The effect of multiple micronutrient fortified milk consumption on vitamin D
      status among school-age children in rural region of Morocco.
AB  - Vitamin D deficiency is a health problem in both developed and developing
      countries. The aim of this study was to determine the effect of multivitamin
      fortified milk consumption on vitamin D status among children living in the
      mountainous region of Morocco. 7 to 9 years old children (n=239; 49% of girls vs
      51% of boys) have participated in a double blind longitudinal study, where they
      were divided in two groups: a fortified group who received daily 200 mL of
      fortified Ultra-High Temperature (UHT) milk enriched with 3MUg of vitamin D3 and
      a non-fortified group who received 200 mL of non-fortified UHT milk with a
      natural abundance of vitamin D3 (about 1.5ug). Blood samples were collected three
      times (at baseline, after 4 and 9 months). The average weight, height and BAZ of
      participants were 22.8+/-2.6 kg, 121.5+/-5.2 cm and -0.2+/-0.6 kg/m2
      respectively. At baseline, 47.5% of children had a concentration of 25
      hydroxyvitamin D (25(OH)D) below 50 nmol/L. At the end of the study the
      prevalence of vitamin D <50 nmol/L decreased significantly by 37.6 % in the
      fortified group. These results reveal prevalent vitamin D insufficiency (<50
      nmol/L) during winter among rural Moroccan school age children, which seems to be
      better improved by consuming the fortified milk instead of non-fortified one.

PMID- 30286304
TI  - Adolescents with autism show typical fMRI repetition suppression, but atypical
      surprise response.
AB  - Recent theoretical frameworks have hypothesized that autism spectrum disorder
      (ASD) may be marked by an altered balance between sensory inputs and prior
      knowledge-the so-called hypoprior hypothesis. Yet evidence regarding such an
      altered balance is mixed. Here, we aimed to test this hypothesis within the
      domain of visual perception, by examining how neural activity in the visual
      system was modulated by stimulus repetition and stimulus expectation in healthy
      and ASD participants. We presented 22 adolescents with ASD and 22 typically
      developing (TD) adolescents with pairs of object stimuli, while measuring brain
      activity using functional magnetic resonance imaging (fMRI). Stimulus pairs could
      be stimulus repetitions or not and could be expected or not. We examined neural
      activity in early (V1) and object-selective (LOC) visual cortex. Both ASD and TD
      individuals showed robust and equal repetition suppression in LOC. By contrast,
      ASD and TD groups showed a different response to expected versus unexpected
      stimuli, specifically in V1. Thereby, our results suggest that while the more
      automatic modulation of activity by repetition is unaffected in ASD, there is
      some evidence that the balance between sensory evidence and prior knowledge may
      indeed be altered in early visual cortex of ASD.

PMID- 30286305
TI  - One versus two eyes makes a difference! Early face perception is modulated by
      featural fixation and feature context.
AB  - The N170 event-related potential component is an early marker of face perception
      that is particularly sensitive to isolated eye regions and to eye fixations
      within a face. Here, this eye sensitivity was tested further by measuring the
      N170 to isolated facial features and to the same features fixated within a face,
      using a gaze-contingent procedure. The neural response to single isolated eyes
      and eye regions (two eyes) was also compared. Pixel intensity and contrast were
      controlled at the global (image) and local (featural) levels. Consistent with
      previous findings, larger N170 amplitudes were elicited when the left or right
      eye was fixated within a face, compared to the mouth or nose, demonstrating that
      the N170 eye sensitivity reflects higher-order perceptual processes and not
      merely low-level perceptual effects. The N170 was also largest and most delayed
      for isolated features, compared to equivalent fixations within a face.
      Specifically, mouth fixation yielded the largest amplitude difference, and nose
      fixation yielded the largest latency difference between these two contexts,
      suggesting the N170 may reflect a complex interplay between holistic and featural
      processes. Critically, eye regions elicited consistently larger and shorter N170
      responses compared to single eyes, with enhanced responses for contralateral eye
      content, irrespective of eye or nasion fixation. These results confirm the
      importance of the eyes in early face perception, and provide novel evidence of an
      increased sensitivity to the presence of two symmetric eyes compared to only one
      eye, consistent with a neural eye region detector rather than an eye detector per
      se.

PMID- 30286306
TI  - Changes in acceptance of dating violence and physical dating violence
      victimization in a longitudinal study with teens.
AB  - Teen dating violence is a pervasive issue in adolescence and has been linked to
      maladjustment (Temple, Shorey, Fite et al., 2013). Physical dating violence is a
      particularly significant problem with one in five adolescents reporting
      experiencing physical teen dating violence (TDV; Wincentak et al., 2017).
      Acceptance of violence has been suggested to increase the risk of TDV; however,
      most studies to date have been cross-sectional. The purpose of the current study
      is to examine patterns of acceptance of dating violence and TDV victimization
      across time. Participants were ethnically diverse teenagers (N = 1042; ages 13
      18) who were followed over a four-year period. Multivariate latent growth curve
      modeling techniques were used to determine trajectories of physical TDV
      victimization and attitudes accepting of dating violence. Results showed two
      trajectories for physical TDV victimization, linear and quadratic, and two
      trajectories for acceptance of dating violence, non-linear and quadratic.
      Parallel models investigating the interplay between TDV victimization and
      acceptance demonstrated two possible trends; however, we did not find any
      evidence for a longitudinal relationship between the two variables, suggesting
      that change in acceptance was not related to change in physical TDV
      victimization. Instead, our results suggest a significant amount of heterogeneity
      in these trajectories. These findings suggest studies are still needed to further
      explore longitudinal patterns of TDV to better understand how to reduce the risk
      of teen dating violence.

PMID- 30286307
TI  - A universal method to create surface patterns with extreme wettability on metal
      substrates.
AB  - Extreme wettability surfaces have attracted more and more attention due to their
      practical applications, however, few reports have shown a universal method to
      create surface patterns with extreme wettability on a variety of metals. In this
      paper, a mask-assisted dual-chemical-processing approach without special
      modification is used to prepare the extreme wettability patterns on various metal
      substrates. Fabrication of superhydrophilic-superhydrophobic patterns on five
      kinds of metal substrates of Al, Ti, steel, Zn and Mg alloy proved the
      versatility of this method. The extreme wettability patterns prepared by this
      method were applied to fog harvest and we found the big differences in the
      collection efficiency of various metal surface patterns.

PMID- 30286308
TI  - Self-cleaning, stain-resistant and anti-bacterial superhydrophobic cotton fabric
      prepared by simple immersion technique.
AB  - In this paper, superhydrophobicity of cotton fabric was produced by simple
      immersion method in non-fluorinated hexadecyltrimethoxysilane solution. Modified
      cotton fabric showed repellency to water and liquids with surface tension of more
      than 47 mN/m, with a static contact angle of more than 150 degrees  and tilt
      angle of less than 10 degrees . The mechanical, chemical, thermal, and UV
      stability of superhydrophobic cotton fabric was evaluated. Modified cotton fabric
      exhibited the self-cleaning and stain-resistant properties. It also showed that
      it could be used for oil-water separation application with separation efficiency
      of about 99%. Additionally, the modified cotton fabric exhibited anti-bacterial
      properties. This approach is facile, economical, and eco-friendly and can be
      applied for household and industrial applications.

PMID- 30286309
TI  - Datura-like Ni-HG-rGO as highly efficient electrocatalyst for hydrogen evolution
      reaction in alkaline conditions.
AB  - Development of highly-active and noble-metal-free electrocatalysts for hydrogen
      evolution reactions is a challenge, and optimizing the structure and the
      composition of the relative materials is critical to obtain the high-quality
      catalysts. Ni-based compounds are being explored as noble-metal-free
      electrocatalysts in hydrogen evolution reactions but the Ni-based needs to be
      modified effectively. In this work, we co-electrodeposited Ni nanoparticles,
      hydrophilic graphene and graphene oxide layers on Ni foam to synthesize Ni-HG
      rGO/NF catalysts. It was presented a Datura-like shape allowing for high
      performance with current densities of -10 and -100 mA cm-2 for HER at
      overpotentials of -50 and -132 mV, a low Tafel slope of -48 mV dec-1 and
      excellent long-term stability in 1.0 M NaOH solution. These results demonstrate
      that the Ni-HG-rGO/NF electrode can be a competitive electrode materials for HER
      in alkaline conditions.

PMID- 30286310
TI  - Carrier-free core-shell nanodrugs for synergistic two-photon photodynamic therapy
      of cervical cancer.
AB  - Carrier-free nanodrugs named BCNPs were prepared by the coassembly of 2,5-bis(4
      (diethylamino)benzylidene)cyclopentanone (BDBC) and curcumin (CCM) in the absence
      of surfactants. The as-synthesized BCNPs possess high dispersity and stability in
      aqueous media, along with favorable photostability and good biocompatibility.
      Comparing with their counterparts BDBC and CCM, BCNPs exhibit higher singlet
      oxygen yield and better two-photon photodynamic therapy (PDT) efficacy. Moreover,
      BCNPs display dramatically enhanced ability for inhibiting the growth of HeLa
      cells, which benefits from the synergistic treatment of BDBC and CCM under the
      irradiation of 450/808 nm. This work highlights the potential of using simple
      coassembly strategy to codelivery of multiple drugs in one single formulation for
      cancer therapy.

PMID- 30286311
TI  - Salt and water co-assisted exfoliation of graphite in organic solvent for
      efficient and large scale production of high-quality graphene.
AB  - Graphene has attracted enormous attention due to its unique physical properties
      and attractive applications in many fields. However, it is an ongoing challenge
      to develop a facile and low-cost method for the large scale preparation of high
      quality graphene (HQGr). In this work, we have developed an improved liquid-phase
      exfoliation method to mass produce HQGr. This method is quite simple but
      efficient by exfoliation of graphite in organic solvent with the co-assistance of
      sodium citrate and water. Remarkably, the concentration of as-exfoliated HQGr was
      as high as 0.71 mg/mL under optimal conditions, while the oxygen content in HQGr
      was only 2.39%. After annealing at 500  degrees C for 2 h in argon atmosphere,
      the mean conductivity of annealed HQGr was as high as 1.4 * 104 S m-1. Therefore,
      this facile method for liquid-phase exfoliation of graphite has excellent
      potential in the industrial-scale production of HQGr for numerous applications in
      energy storage, optical and electronic fields.

PMID- 30286312
TI  - Assessment of quiet T2 weighted PROPELLER sequence in pediatric abdominal
      imaging.
AB  - INTRODUCTION: Elevated acoustic noise during Magnetic Resonance Imaging (MRI) has
      been associated with patient anxiety and altered cochlear function. Acoustic
      Reduction Technique (ART) T2 weighted (T2w) periodically rotated overlapping
      parallel lines with enhanced reconstruction (PROPELLER) has been studied in brain
      MR but not abdominopelvic imaging. The purpose of our study was to evaluate the
      image quality and acoustic noise level of ART T2w PROPELLER sequence in
      comparison with the conventional T2w PROPELLER sequence in pediatric abdomino
      pelvic imaging. METHODS: Eleven consecutive pediatric patients undergoing
      abdomino-pelvic MRI were scanned on a 3 Tesla magnet using standard and ART T2w
      PROPELLER sequences. After scanning completion, objective sound level
      measurements were performed with a sound level meter and microphone. Mann-Whitney
      U test was used for a non-parametric two-tailed statistical analysis of
      acoustics, image rating and scan time with significance level set to 0.05.
      Overall inter-rater agreement was calculated using Cohen's kappa coefficient.
      RESULTS: Eleven pediatric patients (4 females and 7 males) between 26 days and 18
      years of age (mean = 10.0, SD = 5.8) were included. ART T2w produced lower levels
      of acoustic noise than standard technique in a comparison of mean decibel
      readings from eleven trials of standard and ART T2w (p value = 0.00008). Streak
      artifacts were rated greater in ART T2w by both raters (p-value = 0.00278 and
      0.00252). There was no significant difference in bile duct blurring, respiratory
      ghosting, pulsation, fat suppression or hepatic parenchymal depiction.
      CONCLUSION: Presence of additional streaking artifacts should be considered along
      with the benefit of reduced acoustic noise from ART T2w.

PMID- 30286313
TI  - Diffusion tensor imaging and quantitative susceptibility mapping as diagnostic
      tools for motor neuron disorders.
AB  - PURPOSE: Diffusion tensor imaging (DTI) and quantitative susceptibility mapping
      (QSM) have been proposed as methods to aid in the diagnosis of amyotrophic
      lateral sclerosis (ALS) and primary lateral sclerosis (PLS), both diseases
      affecting upper motor neurons. We test the performance of DTI and QSM alone and
      in combination to distinguish patients with diseases affecting upper motor
      neurons (ALS/PLS) from patients with other motor symptom-predominant neurologic
      disorders. METHODS: 3.0 Tesla MRI with DTI and QSM in patients referred to a
      subspecialty neurology clinic for evaluation of motor symptom-predominant
      neurologic disorders were retrospectively reviewed. Corticospinal tract
      fractional anisotropy and maximum motor cortex susceptibility were measured.
      Subjects were categorized by diagnosis and imaging metrics were compared between
      groups using Student's t-tests. Receiver operating characteristic curves were
      generated for imaging metrics alone and in combination. RESULTS: MRI scans for 43
      patients with ALS or PLS and 15 patients with motor symptom predominant, non
      upper motor neuron disease (mimics) were reviewed. Fractional anisotropy was
      lower (0.57 vs. 0.60, p < 0.01) and maximum motor cortex magnetic susceptibility
      higher (64.4 vs. 52.7, p = 0.01) in patients with ALS/PLS compared to mimics.
      There was no significant difference in area under the curve for these metrics
      alone (0.73, 0.63; p > 0.05) or in combination (0.75; p > 0.05). CONCLUSION: We
      found significant differences in DTI and QSM metrics in patients with diseases
      affecting upper motor neurons (ALS/PLS) compared to mimics, but no significant
      difference in the performance of these metrics in diagnosing ALS/PLS compared to
      mimics.

PMID- 30286314
TI  - Functional movement disorders of the face: A historical review and case series.
AB  - Functional facial dystonia or spasm has, in recent years, been recognised as a
      relatively common form of functional movement disorder. We describe historical
      'forgotten' neurological literature indicating that this was a well described
      phenomenon in the late 19th and early 20th century but subsequently faded from
      awareness. We add data from our own series of 41 patients with functional facial
      dystonia to explore the clinical features and associated comorbidities of
      patients with this movement disorder.

PMID- 30286315
TI  - Dietary patterns and colorectal cancer risk in Zimbabwe: A population based case
      control study.
AB  - BACKGROUND: The rising incidence of colorectal cancer in sub-Saharan Africa may
      be partly caused by changing dietary patterns. We sought to establish the
      association between dietary patterns and colorectal cancer in Zimbabwe. METHODS:
      One hundred colorectal cancer cases and 200 community-based controls were
      recruited. Data were collected using a food frequency questionnaire, and dietary
      patterns derived by principal component analysis. Generalised linear and logistic
      regression models were used to assess the associations between dietary patterns,
      participant characteristics and colorectal cancer. RESULTS: Three main dietary
      patterns were identified: traditional African, urbanised and processed food. The
      traditional African diet appeared protective against colorectal cancer (Odds
      Ratio (OR) 0.35; 95% Confidence Interval (CI), 0.21 - 0.58), which had no
      association with the urban (OR 0.68; 95% CI, 0.43-1.08), or processed food (OR
      0.91; 0.58-1.41) patterns. The traditional African diet was associated with rural
      domicile, (OR 1.26; 95% CI, 1.00-1.59), and a low income (OR1.48; 95% CI, 1.06
      2.08). The urbanised diet was associated with urban domicile (OR 1.70; 95% CI,
      1.38-2.10), secondary (OR 1.30; 95% CI, 1.07-1.59) or tertiary education (OR
      1.48; 95% CI, 1.11-1.97), and monthly incomes of $201-500 (OR 1.30; 95% CI, 1.05
      1.62), and the processed food pattern with tertiary education (OR 1.42; 95% CI,
      1.05-1.92), and income >$1000/month (OR 1.48; 95% CI, 1.02-2.15). CONCLUSION: A
      shift away from protective, traditional African dietary patterns may partly
      explain the rising incidence of colorectal cancer in sub-Saharan Africa.

PMID- 30286316
TI  - Body weight support through a walking cane in inexperienced users with knee
      osteoarthritis.
AB  - BACKGROUND: Walking canes are a self-management strategy recommended for people
      with knee osteoarthritis (OA) by clinical practice guidelines. Ensuring that an
      adequate amount of body-weight support (%BWS) is taken through the walking cane
      is important as this reduces measures of knee joint loading. RESEARCH QUESTION:
      1) How much body weight support do people with knee OA place through a cane? 2)
      Do measures of body weight support increase following a brief simple training
      session? METHODS: Seventeen individuals with knee pain who had not used a walking
      cane before were recruited. A standard-grip aluminum cane was then used for 1
      week with limited manufacturer instructions. Following this, participants were
      evaluated using an instrumented force-measuring cane to assess body weight
      support (% total body weight) through the cane. Force data were recorded during a
      430-metre walk undertaken twice; once before 10 min of cane training administered
      by a physiotherapist, and once immediately after training. Measures of BWS (peak
      force, average force, impulse equal to the average cane force times duration, and
      cane-ground contact duration) were extracted. Using bathroom scales, training
      aimed to take at least 10% body weight support through the cane. RESULTS: Before
      training, the average peak BWS was 7.2 +/- 2.5% of total body weight. Following
      10 min of training, there was a significant increase in average peak BWS by 28%,
      average BWS by 25%, and BWS impulse by 54% (p < 0.05). However, individual BWS
      responses to training were variable. Duration of cane placement increased by 22%
      after training (p = 0.02). Timing of peak BWS through the cane occurred at 51% of
      contact phase before training, and at 53% after training (p = 0.05).
      SIGNIFICANCE: A short training session can increase the transfer of body weight
      through a walking cane. However, more sophisticated feedback may be needed to
      achieve target levels of BWS.

PMID- 30286317
TI  - Changes in the symmetry of external perturbations affect patterns of muscle
      activity during gait initiation.
AB  - BACKGROUND: Gait initiation is associated with changes in the steady state and
      experiencing an external perturbation during initiation of gait could further
      threaten balance stability. RESEARCH QUESTION: The aim of the study was to
      investigate if changes in the symmetry of the perturbations affect patterns of
      muscle activity during gait initiation. METHODS: Eleven young health participants
      were instructed to stand on the force platform and wait for the instruction of
      taking a right step, left step or stand still while experiencing a pendulum
      perturbation applied to the back of both shoulders (symmetric), back of the right
      shoulder (asymmetric) or no perturbations. Bilateral electromyographic activity
      (EMG) of dorsal and ventral muscles, moments of the pendulum release and
      perturbation impact, center of pressure (COP) displacements and pelvic movements
      were recorded and analyzed before and after the onset of the perturbation.
      RESULTS: Taking the right/left step in presence of symmetric perturbation did not
      affect the temporal sequence of COP and pelvic movements. The onset of COP and
      pelvic movement occurred before the perturbation impact at the shoulder levels.
      The factors of step and perturbation did not significantly affect integrals of
      bilateral muscles at the pendulum release. After the pendulum release, ventral
      and dorsal EMG integrals of the trunk, thigh, and shank segments increased or
      decreased corresponding to the swing and stance leg. Changes in muscle activities
      were also associated with the symmetric or asymmetric perturbations before and
      after the perturbation impact. SIGNIFICANCE: The outcome of the study provides
      information about strategies used to coordinate the activity of muscles while
      body perturbations are induced during gait initiation.

PMID- 30286318
TI  - Endosymbiosis-related changes in ultrastructure and chemical composition of
      Chlorella variabilis (Archaeplastida, Chlorophyta) cell wall in Paramecium
      bursaria (Ciliophora, Oligohymenophorea).
AB  - Chlorella variabilis, a symbiotic alga, is usually present in the cytoplasm of
      Paramecium bursaria, although it can be cultured in host-free conditions.
      Morphological and chemical properties of its cell wall were compared between its
      free-living and symbiotic states. Transmission electron microscopy (quick
      freezing and freeze-substitution methods) revealed that the cell wall thickness
      of symbiotic C. variabilis was reduced to about half that of the free-living one.
      Chemical properties of the cell wall were examined by treatment with three
      fluorescent reagents (calcofluor white M2R, FITC-WGA, and FITC-LFA) having
      specific binding affinities to different polysaccharides. When the algae were re
      introduced into Paramecium host cells, calcofluor fluorescence intensity reduced
      by about 50%. Calcofluor stains beta-d-glucopyranose polysaccharides such as
      cellulose, N-acetylglucosamine, sialic acid, and glycosaminoglycans. Because
      treatment with cellulase showed no effect on calcofluor fluorescence intensity,
      we consider that cellulose is not majorly responsible for the stainability of
      calcofluor. Staining intensities of FITC-WGA and FITC-LFA were similar in the
      free-living and symbiotic conditions, suggesting that N-acetylglucosamine and
      sialic acid are also not responsible for the reduction in the stainability of
      calcofluor associated with intracellular symbiosis. The amount of
      glycosaminoglycans on the cell wall may decrease in C. variabilis present in the
      cytoplasm of P. bursaria.

PMID- 30286319
TI  - Modulating the interhemispheric balance in healthy participants with transcranial
      direct current stimulation: No significant effects on word or sentence
      processing.
AB  - Patient studies and brain stimulation evidence suggest that language processing
      can be enhanced by altering the interhemispheric balance: namely, preferentially
      enhancing left-hemisphere activity while suppressing right-hemisphere activity.
      To our knowledge, no study has yet compared the effects of such bilateral brain
      stimulation to both logically necessary control conditions (separate left- and
      right-hemisphere stimulation). This study did so in a between-group sham
      controlled design, applying transcranial direct current stimulation over Broca's
      area and/or its homologue in 72 healthy participants. The effects were measured
      not only in a single-word-level task but also in a sentence-level task, rarely
      tested previously. We did not find either any significant overall effects of
      stimulation or greater stimulation effects in the bilateral compared to control
      groups. This null result, obtained in a large sample, contributes to the debate
      on whether tDCS can modulate language processing in healthy individuals.

PMID- 30286320
TI  - Immunomodulatory injectable silk hydrogels maintaining functional islets and
      promoting anti-inflammatory M2 macrophage polarization.
AB  - Islet transplantation is considered the most promising treatment for type 1
      diabetes. However, the clinical success is limited by islet dysfunction in long
      term culture. In this study, we have utilized the rapid self-gelation and
      injectability offered by blending of mulberry silk (Bombyx mori) with non
      mulberry (Antheraea assama) silk, resulting in a biomimetic hydrogel. Unlike the
      previously reported silk gelation techniques, the differences in amino acid
      sequences of the two silk varieties result in accelerated gelation without
      requiring any external stimulus. Gelation study and rheological assessment
      depicts tuneable gelation as a function of protein concentration and blending
      ratio with minimum gelation time. In vitro biological results reveal that the
      blended hydrogels provide an ideal 3D matrix for primary rat islets. Also, A.
      assama fibroin with inherent Arg-Gly-Asp (RGD) shows significant influence on
      islet viability, insulin secretion and endothelial cell maintenance. Furthermore,
      utility of these hydrogels demonstrate sustained release of Interleukin-4 (IL-4)
      and Dexamethasone with effective M2 macrophage polarization while preserving
      islet physiology. The immuno-informed hydrogel demonstrates local modulation of
      inflammatory responses in vivo. Altogether, the results exhibit promising
      attributes of injectable silk hydrogel and the utility of non-mulberry silk
      fibroin as an alternative biomaterial for islet encapsulation.

PMID- 30286321
TI  - In silico screening of cancer-associated mutations in the HSA domain of BRG1 and
      its role in affecting the Arp-HSA sub-complex of SWI/SNF.
AB  - SWI/SNF (SWItch/Sucrose Non-Fermentable) complexes regulate the gene expression
      programs by remodeling the nucleosome architecture of the chromatin functional
      elements. These large multi-component complexes comprise eight or more subunits
      and are conserved from yeast to human. Noticeably, nuclear actin and actin
      related proteins (Arps) are an integral part of these complexes and are known to
      directly interact with the helicase-SANT-associated (HSA) domain of ATPase
      subunit. Recently, SWI/SNF subunits are gaining importance because of the
      prevalence of cancer-causing mutations associated with them. The functional
      characterization of the mutations in the SWI/SNF subunits is important for
      understanding their role in tumorigenesis and identifying potential therapeutic
      strategies. To study the actin-related complex of human SWI/SNF and the cancer
      associated mutations interfering Arp assembly with the ATPase subunit, we
      modelled the structure of the beta-actin-BAF53A-HSA complex based on the yeast
      Arp-HSA complex (PDB ID: 4I6M). Seven deleterious mutations in the HSA domain of
      BRG1 were identified based on the functional screening of cancer-associated
      mutations in the COSMIC database. Detailed structural analysis of the six
      mutations (R466H, R469W, Y489C, K502N, R513Q and R521P) based on molecular
      dynamics (MD) simulations reveal the distinct effect of each mutation in
      destabilizing the structure of the Arp-HSA complex. Predominantly we could notice
      the long-range effect of the HSA mutations in influencing the dynamics of the Arp
      subunits.

PMID- 30286322
TI  - In silico analysis of Pax6 protein glycosylation in vertebrates.
AB  - Pax6 is a transcription factor that involves in the formation of the eye, brain,
      and central nervous system in vertebrates. Due to various roles in the eye
      morphogenesis, Pax6 interacts with DNA and various transcription factors via post
      translational modifications. Post-translational modifications of Pax6 have been
      studied extensively but there is a paucity of information about the
      glycosylation. Here, we focused on predicting the glycosylation positions of Pax6
      protein in vertebrates. Also, 3D protein and glycoprotein models were generated
      using I-TASSER and GLYCAM servers in order to understand the effect of
      glycosylation on the Pax6 protein structure. We predicted N-glycosylation, mucin
      type O-glycosylation, O-alpha-GlcNAcylation, and O-beta-GlcNAcylation positions
      on Pax6 protein besides O-GlcNAc modification. Moreover, we found ying-yang
      positions suggesting the presence of O-GlcNAcylation/phosphorylation competition
      in Pax6. As to 3D glycoprotein models of Pax6, Ser24, Ser65, and Ser74 residues
      at the PD domain of Pax6 protein was evaluated as a strong candidate for the DNA
      binding site. We suggest that determination of the glycosylation positions on 3D
      glycoprotein model will facilitate the understanding of glycosylation role on
      Pax6 protein interactions in transcription and intracellular activities.

PMID- 30286323
TI  - Plasticity in the hormonal response to cold stress in the invasive plant
      Carpobrotus edulis.
AB  - Cold stress response is mediated by multiple signaling pathways with complex
      interactions, among which phytohormones may play a role. We explored changes in
      the contents of phytohormones, including abscisic acid, jasmonic acid, salicylic
      acid, auxin, cytokinins, gibberellins and melatonin, along with stress tolerance
      markers in an invasive halophyte, Carpobrotus edulis in response to chilling. In
      a first experiment, plants were exposed to mean daily temperatures from 10 
      degrees C to 5  degrees C during a cold wave in an experimental garden. In a
      second experiment, plants were subject to slowly decreasing temperatures, from 20
      to 5  degrees C, in a climatic chamber. Although the cold response in both
      experiments was associated with a similar extent of leaf desiccation, hormonal
      variations differed. Cold stress reduced melatonin contents, while it increased
      salicylic acid contents in the experimental garden. Rather, transient increases
      in the contents of melatonin occurred in parallel with sustained increases in the
      contents of abscisic acid and cytokinins in the climatic chamber. In both
      experiments, plants were able to prevent cold-induced increases in lipid
      peroxidation and any eventual damage to the photosynthetic apparatus. We conclude
      that (i) the hormonal response to chilling in C. edulis is strongly dependent on
      time exposure to low temperatures, severity of stress, as well as other
      environmental conditions, (ii) the hormonal response of this plant species to low
      temperatures is very plastic, thus underlining its great capacity for cold
      acclimation.

PMID- 30286324
TI  - Proteome of olive non-glandular trichomes reveals protective protein network
      against (a)biotic challenge.
AB  - Olive is one of the most important fruit crop trees in the history of
      Mediterranean because of the high quality oil. Olive oil has a well-balanced
      fatty acid composition along with biophenols, which make it exceptional in human
      diet and provide an exceptional value to the olive oil. Leaf non-glandular
      peltate trichomes are specialized cell types representing a protective barrier
      against acute environmental conditions. To characterize the proteome of this
      highly differentiated cell type, we performed a comparative proteomic analysis
      among isolated trichomes and trichome-less leaves. Proteins were separated and
      identified using the 2-DE MALDI-TOF/MS method. A number of enzymes involved in
      abiotic and biotic stress responses are present and may be responsible for the
      adaptation to prolonged adverse environmental conditions. The results show that
      this highly differentiated cell type is physiologically active fulfilling the
      demands of the trichomes in furnishing the leaf with a highly protective
      mechanism.

PMID- 30286325
TI  - Neurometabolic abnormalities in the associative striatum in antipsychotic-naive
      first episode psychosis patients.
AB  - Schizophrenia is a chronic, often progressive, disorder. Understanding the
      underlying neurobiology present in the early stages of the illness is as a
      pivotal step in designing targeted interventions aimed at arresting disease
      progression. The aim of our study was to examine neurometabolic changes in the
      dopamine rich associative striatum in medication-naive first episode psychosis
      (FEP). We quantified neurometabolites in 14 FEP and 18 healthy controls (HC)
      matched on key demographic characteristics. Spectra from the voxel in the left
      associative striatum were acquired using a PRESS sequence (TR/TE = 2000/80 ms;
      512 averages). MRS data were quantified in the time domain with AMARES in jMRUI.
      Choline was significantly elevated in FEP compared to HC. No significant
      alterations in other metabolites were observed. We did not observe correlations
      between metabolite levels and clinical characteristics in FEP. Here, we
      demonstrated elevated choline and a disruption of the relationship between N
      acetyl-aspartate and Glx (glutamate + glutamine) in medication-naive FEP patients
      in the left striatum indicating possible mitochondrial, membrane and glial
      dysfunction as an underlying pathological phenomenon. In addition, striatal
      choline shows promise as a biomarker for FEP that may have utility in clinical
      trials investigating target engagement in experimental regimens.

PMID- 30286327
TI  - Expression of the Annexin A1 and its correlation with matrix metalloproteinases
      and the receptor for formylated peptide-2 in diffuse astrocytic tumors.
AB  - Astrocytomas represent the majority of cerebral gliomas. Studies show that the
      anti-inflammatory protein Annexin-A1 (ANXA1) is associated with the tumor
      invasion process and that its actions can be mediated by the receptor for
      formylated peptides (FPR). Therefore, we evaluated the expression of ANXA1, the
      receptor FPR2 and matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) in brain
      astrocytomas. Detection of proteins was performed in sections of diffuse
      astrocytomas (grade II), anaplastic astrocytomas (grade III) and glioblastomas
      (GBM, grade IV) and quantifications were made by densitometry. Our analyses
      showed increased expression of ANXA1 in astrocytomas of all grades, but
      especially in GBM. The expression of FPR2 is similar to that found for ANXA1,
      being higher in GBM. Immunostaining for MMPs is also stronger as the degree of
      malignancy increases, especially with respect to MMP-9. The positive correlation
      between ANXA1/FPR2 and ANXA1/MMP-9 was observed in all tumors studied. The data
      indicate the possible action of ANXA1 and FPR2 on the development and progression
      of astrocytomas, related to increased expression of MMP-9. Thereby, ANXA1 and
      FPR2 are involved in the biology and malignancy of diffuse astrocytic tumors.

PMID- 30286326
TI  - Investigation of PP2A and Its Endogenous Inhibitors in Neuroblastoma Cell
      Survival and Tumor Growth.
AB  - High-risk neuroblastoma continues to carry a poor prognosis. Nearly 50% of these
      tumors relapse following extensive treatment regimens. Protein phosphatase 2A
      (PP2A), a tumor suppressor, has been shown to be downregulated in many human
      cancers via multiple mechanisms including upregulation of its endogenous
      inhibitors, I2PP2A or CIP2A. We hypothesized that inhibition of the endogenous
      PP2A inhibitors or activation of PP2A would decrease tumorigenicity in human
      neuroblastoma cells. Four human neuroblastoma cell lines were utilized.
      Expression of PP2A and its endogenous inhibitors I2PP2A and CIP2A was confirmed
      by immunoblotting. PP2A activation was measured via phosphatase activation assay.
      Multiple parallel methods including siRNA inhibition of the endogenous PP2A
      inhibitors and pharmacologic activation of PP2A were utilized. Cell viability,
      proliferation, migration, and invasion assays were performed. In vivo studies
      were utilized to determine the effects of PP2A activation on neuroblastoma tumor
      growth. Inhibition of the endogenous inhibitors of PP2A or pharmacologic
      activation of PP2A with the PP2A activator FTY720 led to decreased neuroblastoma
      cell viability, proliferation, migration, and invasion. Treatment of mice bearing
      SK-N-AS or SK-N-BE(2) neuroblastoma tumors with FTY720 resulted in a significant
      decrease in tumor growth compared to vehicle-treated animals. In conclusion,
      activation of PP2A may provide a novel therapeutic target for neuroblastoma.

PMID- 30286328
TI  - Exploratory analysis of mediators of the relationship between childhood
      maltreatment and suicidal behavior.
AB  - INTRODUCTION: Suicide is a major public health concern. One consistently cited
      risk factor for suicide is childhood maltreatment, which also may play a role in
      the transition from suicidal ideation to suicidal behavior. METHOD: The current
      study aimed to examine the relationship between childhood maltreatment and
      suicide attempts during adolescence (N = 4834; 52.1% female; 67.5% Caucasian).
      Data from the U.S. National Longitudinal Study of Adolescent Health were
      utilized. Forty-six theoretically-relevant risk factors were explored as
      potential mediators of this relationship using an exploratory mediation data
      analytic method. RESULTS: Results demonstrated a significant childhood
      maltreatment - suicide attempt relationship only among females. After considering
      demographics and suicidal ideation, having received counseling in the previous 12
      months was the most influential mediator, followed by having a friend attempt
      suicide in the previous 12 months. CONCLUSIONS: These findings highlight
      potential gender differences in the relationship between childhood maltreatment
      and later suicide attempts, and, moreover, the importance of assessing for recent
      exposure to peer suicidal behavior in suicide risk assessments.

PMID- 30286329
TI  - Brief report: A qualitative evidence synthesis of the psychological processes of
      school-based expressive writing interventions with adolescents.
AB  - INTRODUCTION: Expressive writing interventions consist of brief writing sessions
      on thoughts and emotions and are known to yield positive benefits on adolescents'
      mental health. However, the psychological mechanisms explaining these effects are
      not clear. METHOD: This review explored the psychological processes underlying
      school-based expressive writing interventions with adolescents. A thematic
      synthesis of qualitative research consisted of identifying, appraising and
      summarizing the qualitative evidence of eligible studies. RESULTS: Only six of
      the 510 identified studies met the inclusion criteria of this review. Results
      provide some validation for cognitive-processing, emotion-regulation, and
      disinhibition as psychological mechanisms underlying school-based expressive
      writing with adolescents. CONCLUSIONS: However, these conclusions are still
      preliminary because of the paucity of the qualitative evidence found, both in
      quantity and quality. We recommend that more rigorous and in-depth qualitative
      research be undertaken to: 1) explore adolescents' subjective experience about
      the expressive writing intervention, using in-depth individual interviews; 2)
      thoroughly assess the content of students' texts written during the intervention;
      and 3) document the process of expressive writing interventions through
      observational methods. The results of such investigations would support the
      development and implementation of school-based expressive writing-type of
      interventions adapted to adolescents.

PMID- 30286330
TI  - Iron overload in myelodysplastic syndromes: Evidence based guidelines from the
      Canadian consortium on MDS.
AB  - In 2008 the first evidence-based Canadian consensus guideline addressing the
      diagnosis, monitoring and management of transfusional iron overload in patients
      with myelodysplastic syndromes (MDS) was published. The Canadian Consortium on
      MDS, comprised of hematologists from across Canada with a clinical and academic
      interest in MDS, reconvened to update these guidelines. A literature search was
      updated in 2017; topics reviewed include mechanisms of iron overload induced
      cellular damage, evidence for clinical endpoints impacted by iron overload
      including organ dysfunction, infections, marrow failure, overall survival, acute
      myeloid leukemia progression, and endpoints around hematopoietic stem-cell
      transplant. Evidence for an impact of iron reduction on the same endpoints is
      discussed, guidelines are updated, and areas identified where evidence is
      suboptimal. The guidelines address common questions around the diagnosis, workup
      and management of iron overload in clinical practice, and take the approach of
      who, when, why and how to treat iron overload in MDS. Practical recommendations
      for treatment and monitoring are made. Evidence levels and grading of
      recommendations are provided for all clinical endpoints examined.

PMID- 30286331
TI  - TLE1 as an indicator of adverse prognosis in pediatric acute lymphoblastic
      leukemia.
AB  - PURPOSE: Acute lymphoblastic leukemia (ALL) is the most common type of cancer in
      children, and despite the high rate of cure (over 80%) it still has a big impact
      on morbidity and mortality. The Transducin-like enhancer of split 1 (TLE1), a
      transcriptional corepressor, has been described as dysregulated and recently
      emerged as a tumor marker in several cancer types, including hematologic
      malignancies. METHODS: In the present study TLE1 gene expression was evaluated by
      RT-qPCR. A total of 60 consecutive pathological ALL samples and 8 normal bone
      marrow samples were included. Associations between TLE1 levels and
      clinicopathological features were estimated using Mann-Whitney tests. RESULTS:
      TLE1 mRNA levels were significantly diminished in ALL samples when compared to
      normal counterparts (fold change -1.45, p-value 0.039). Lower TLE1 expression
      levels were associated with poorer prognostic features such as age at diagnosis
      (<1 or >9 years-old), absence of the Common Acute Lymphoblastic Leukemia Antigen
      (CALLA) and high white cell count. Considering immunophenotype, decreased
      expression of TLE1 was only evident for T-cell ALL, what was validated using gene
      expression profiling data available in public repositories. No associations with
      event or overall survival were observed. However, TLE1 expression was
      statistically different between patients who achieved complete clinical remission
      (CCR) from those that relapsed or died. CONCLUSION: These data are of particular
      interest and give support for a plausible role of TLE1 as a tumor suppressor in T
      cell ALL. Moreover, the prognostic value of this corepressor may assist ALL
      treatment stratification and suggest the need of alternative regimens.

PMID- 30286332
TI  - Magnetic resonance angiography contrast enhancement and combined 3D visualization
      of cerebral vasculature and white matter pathways.
AB  - Recently, in diffusion magnetic resonance imaging, the reconstruction and three
      dimensional rendering of white matter pathways have been introduced to clinical
      routine protocols. In a number of clinical situations, for example the
      preoperative analysis of vascular pathologies, the assessment of spatial
      relations between vascular structures and nearby fiber pathways is of vital
      interest for treatment planning. In this paper, we present an approach to the
      integrated vessel and fiber visualization, based on a novel vascular contrast
      enhancement operator for Magnetic Resonance Angiography (MRA) datasets. We
      propose a 3D dynamic programming method, allowing contrast enhancement of
      vascular structures and suppression of partial voluming effects at vessel
      borders. This makes it easier to visualize vascular structures by realtime volume
      rendering with surface shading. In contrast to maximum intensity projection, the
      method provides better depth cues and allows for easier spatial orientation. The
      integration of tractography-generated fibers as streamlines or streamtubes with
      correct visibility computation is performed by a combined volume and geometry
      renderer. In situations where tractography fails to provide reliable results, we
      use a line integral convolution method to assess white matter structures. In this
      manner, the spatial relations of vessels to fiber structures can be depicted by
      three-dimensional visualizations. We evaluate our approach with clinical data
      from patients with arteriovenous malformations, stenoses, aneurysms, and from
      healthy volunteers.

PMID- 30286333
TI  - Deep learning nuclei detection: A simple approach can deliver state-of-the-art
      results.
AB  - BACKGROUND: Deep convolutional neural networks have become a widespread tool for
      the detection of nuclei in histopathology images. Many implementations share a
      basic approach that includes generation of an intermediate map indicating the
      presence of a nucleus center, which we refer to as PMap. Nevertheless, these
      implementations often still differ in several parameters, resulting in different
      detection qualities. METHODS: We identified several essential parameters and
      configured the basic PMap approach using combinations of them. We thoroughly
      evaluated and compared various configurations on multiple datasets with respect
      to detection quality, efficiency and training effort. RESULTS: Post-processing of
      the PMap was found to have the largest impact on detection quality. Also, two
      different network architectures were identified that improve either detection
      quality or runtime performance. The best-performing configuration yields f1
      measures of 0.816 on H&E stained images of colorectal adenocarcinomas and 0.819
      on Ki-67 stained images of breast tumor tissue. On average, it was fully trained
      in less than 15,000 iterations and processed 4.15 megapixels per second at
      prediction time. CONCLUSIONS: The basic PMap approach is greatly affected by
      certain parameters. Our evaluation provides guidance on their impact and best
      settings. When configured properly, this simple and efficient approach can yield
      equal detection quality as more complex and time-consuming state-of-the-art
      approaches.

PMID- 30286334
TI  - Modulatory role of gabapentin against ovalbumin-induced asthma, bronchial and
      airway inflammation in mice.
AB  - Allergic asthma is a type of chronic immune-mediated inflammatory lung disorders
      with constantly increased worldwide prevalence. Gabapentin is an L-type calcium
      channel blocker used essentially as antiepileptic and recently has been indicated
      for management of post-operative and neuropathic pains as an anti-inflammatory.
      The current study was conducted to evaluate the anti-inflammatory and anti
      allergic properties of gabapentin in a mouse-model of Ovalbumin-induced allergic
      asthma. Mice received OVA (10 mg) adsorbed on Al(OH)3 on days 0 and 7 and were
      challenged by exposure to nebulized OVA solution (1%) form days 14-16. Asthma
      induction was associated with significant biochemical, oxidative and inflammatory
      imbalance. Daily oral gabapentin (50 mg/kg), significantly reduced lung
      inflammatory cells counts', serum LDH and catalase activities and lung/body
      weight index. Moreover, gabapentin significantly increased lung GSH concentration
      and enhanced SOD activity. Lung contents of TNFalpha, IL-4 and IL-13
      significantly declined as well. IL-13; is the major contributor to airway hyper
      responsiveness; the charetrestic hallmark of asthma and IL-4; a major
      chemoattractant cytokine. Lung histopathology significantly improved parallel to
      the biochemical improvements. In conclusion; Gabapentin's modulatory effect on IL
      4, IL-13 and TNFalpha activities accounts for the observed anti-inflammatory and
      anti-allergic properties.

PMID- 30286336
TI  - Synthesis of thiomaltooligosaccharides by a thio-click approach.
AB  - Phenyl 2,3,6,2',3',6'-hexa-O-acetyl-4'-S-acetyl-1,4,4'-trithio-beta-d-maltoside
      and its tri-, tetra- and pentasaccharide homologues were prepared by completely
      regio- and stereoselective photoinitiated thiol-ene coupling reactions of 2
      acetoxy-glucal and 4-thioglucose type reaction partners. Complex protecting group
      strategies could be avoided since all thiols and glucals were prepared from a
      single starting material, phenyl 2,3,6-tri-O-acetyl-4-S-acetyl-1,4-dithio-beta-d
      glucopyranoside. The method represents a simple alternative to the known
      syntheses of similar products.

PMID- 30286337
TI  - Multiple sclerosis relapse presenting as an acute cardiomyopathy.
AB  - Multiple sclerosis is increasingly being recognized in association with
      cardiovascular dysfunction, which can manifest with cardiomyopathy, pulmonary
      edema (Kaplan et al., 2015), orthostasis (Kaplan et al., 2015) and other
      complications. Takotsubo cardiomyopathy is a syndrome of acute-onset ventricular
      dysfunction in the absence of obstructive coronary artery disease, which on rare
      occasion has been observed in the setting of demyelinated plaques in the
      brainstem. We report on two cases of Takotsubo cardiomyopathy with medullary
      demyelination secondary to multiple sclerosis.

PMID- 30286335
TI  - Investigation of the H-bond-mediated aglycone delivery reaction in application to
      the synthesis of beta-glucosides.
AB  - In an attempt to refine the H-bond-mediated Aglycone Delivery (HAD) glycosylation
      reaction reported herein is the synthesis of beta-glucosides using an ethylthio
      glucoside donor equipped with the remote 6-O-picoloyl substituent. Upon examining
      various aliphatic, aromatic, and carbohydrate acceptors, it was determined that
      both electronic and steric factors may greatly affect the stereoselectivity of
      the HAD reaction with this donor.

PMID- 30286338
TI  - Implications of irradiance exposure and non-photochemical quenching for multi
      wavelength (bbe FluoroProbe) fluorometry.
AB  - Multi-wavelength fluorometers, such as the bbe FluoroProbe (FP), measure
      excitation spectra of chlorophyll a (Chl-a) fluorescence to infer the abundance
      and composition of phytoplankton communities as well as the concentration of
      chromophoric dissolved organic matter (CDOM). Experiments were conducted on
      laboratory cultures and on natural communities of freshwater phytoplankton to
      determine how the response of phytoplankton to high irradiance might affect
      fluorometric estimates of community composition and concentrations of Chl-a and
      CDOM. Cultures of a representative cyanobacterium, bacillariophyte, synurophyte,
      cryptophyte, and chlorophyte revealed changes in Chl-a excitation spectra as
      irradiance was increased to saturating levels and non-photochemical quenching
      (NPQ) increased. The degree of change and resulting classification error varied
      among taxa, being strong for the synurophyte and cryptophyte but minimal for the
      cyanobacterium. Acute-exposure experiments on phytoplankton communities of
      varying taxonomic composition from five lakes yielded variable results on
      apparent community composition. There was a consistent decrease in CDOM
      estimates, whereas Chl-a estimates were generally increased. Subsequent exposure
      to low PAR relaxed NPQ and tended to reverse the effects of high irradiance on
      composition, total Chl-a, and CDOM estimates. Relaxation experiments on near
      surface communities in a sixth, large lake, Georgian Bay, showed that total Chl-a
      estimates increased by 44% on average when dark treatments were used to relax
      NPQ, though, in contrast to the findings from the small lakes, there was little
      effect on CDOM estimates. We observed a statistically-significant, negative
      linear relationship between the photon flux density of in situ irradiance and the
      accuracy of taxonomic assignment by FP in Georgian Bay. Not discounting the
      correlations between light intensity and the accuracy of the FP that were
      observed in this study, we conclude that the applicability of the reference
      spectra to the system under investigation is a more important consideration than
      variability in natural irradiance conditions.

PMID- 30286339
TI  - Effects of tanning on the stable isotopic compositions of hair.
AB  - We investigated the effect of tanning on the stable isotopic compositions (CNHOS)
      of hair keratin. Samples of hair from polar bear (Ursus maritimus) hides were
      collected before and after the tanning process from a commercial tannery. With
      the exception of sulphur isotopes, tanning did not alter the stable isotopic
      compositions of hair. delta34S values were slightly more positive (1 per mil) in
      hair that had gone through the tanning process, likely as a result of the tanning
      agent, alum (Al2(SO4)3) or exposure to sulphuric acid (H2SO4). This indicates
      that, with the exception of sulphur isotopes, hair keratin is resistant to
      subsequent isotopic alteration by the techniques used in tanning of animal hides
      and thus the original stable isotopic information is likely to be preserved in
      archived samples, such as taxidermic mounts and museum specimens. This is an
      important consideration when dealing with ecological and forensic applications to
      wildlife, such as evaluating provenance or migratory reconstructions, and so will
      assist in conservation efforts and investigations of trafficking and poaching.

PMID- 30286340
TI  - Application of the injury scales in homicides.
AB  - Injury scales have two main applications on homicide investigations, namely, to
      evaluate the severity of the victims' injuries and to identify the profiles of
      the offenders. However, few studies have examined the quality of the various
      injury scales in serving the two purposes. In this study, homicides from Shanghai
      and Wuhan, China (n=439) have been used to examine nine injury scales. The
      results showed that seven out of the nine scales were useful. Compared to one-to
      one homicides, offenders who killed two or more people tended to inflict more
      fatal injuries and made fewer number of attacks on the victims' heads and necks.
      Among all homicide cases, victims of stranger homicides tended to have fewer
      total number of wounds, as well as less severity of wounds on the heads, necks,
      and faces compared to those of intimate partner homicides. As to one-to-one
      homicides, only the severity of wounds on the face could assist to distinguish
      stranger homicides from intimate partner homicides. When a male victim died in a
      one-to-one homicide, the high number of total wounds along with the high number
      and severity of wounds on the head and neck could indicate that the offender was
      a female.

PMID- 30286341
TI  - Applicability and accuracy of Demirjian and Willems methods in a population of
      Eastern Chinese subadults.
AB  - BACKGROUND: To assess the validity of the Demirjian and Willems dental age
      estimation methods in a population of Eastern Chinese 11-18-year-old subadults.
      SAMPLES AND METHODS: A total of 1622 orthopantomograms (787 boys and 835 girls)
      aged from 11.00 to 18.99 years old from a Chinese Han population were evaluated
      in the study. Dental ages were calculated using both Demirjian and Willems
      method. Statistical significance was set at p<0.05 and for each method,
      discrepancies between chronological age (CA) and dental age (DA) were
      statistically analyzed by paired t-tests. Special age interval analysis was
      conducted by Chi-square tests to compare the accuracy of the Demirjian and the
      Willems methods. RESULTS: Demirjian method underestimated CA 0.66+/-1.45 y
      (p<0.001) in boys and 0.62+/-1.61 y (p<0.001) in girls while Willems method
      underestimated 0.90+/-1.32 y (p<0.001) and 0.97+/-1.56 y (p<0.001) in boys and
      girls, respectively. The mean absolute error (MAE) value between the CA and the
      DA (CA-DA) using the Demirjian method and the Willems method were 1.31 and 1.29 y
      for boys, respectively, and 1.35 and 1.43 y for girls, respectively. CONCLUSIONS:
      It is suggested that the Demirjian method was found to be more accurate compared
      with the Willems method. However, the Demirjian method may not be satisfactory
      for 11-18-year-old children of Eastern China. It is recommended that a modified
      Demirjian method for better dental age estimation for Eastern Chinese juvenile
      individuals.

PMID- 30286343
TI  - Screening for lysosomal acid lipase deficiency: A retrospective data mining study
      and evaluation of screening criteria.
AB  - BACKGROUND AND AIMS: Lysosomal acid lipase deficiency (LAL-D) is a lysosomal
      storage disorder. In severe cases, it can cause life-threatening organ failure
      due to lipid substrates accumulation. However, mild phenotypes of this disorder
      are increasingly recognized. The aim of this study is to determine the number of
      missed LAL-D patients in a large pediatric hospital population. METHODS: In a
      retrospective data mining study, the medical files of children, who visited the
      outpatient clinic at a university hospital between 2000 and 2016, with high
      plasma low density lipoprotein cholesterol (LDL-C) levels, were evaluated.
      Previously developed LAL-D screening criteria, with lipid and alanine
      aminotransferase (ALT) values adjusted for children, were used to analyze which
      children are suspect for LAL-D. For suspicion of LAL-D, at least 3 out of 5
      screening criteria had to be met. Subsequently data on presentation and follow-up
      were collected to determine if the clinical picture was compatible with LAL-D.
      RESULTS: We identified 2037 children with high LDL-C levels. Of those, 36
      children complied with >=3 screening criteria. Thirty-one of those had an
      underlying disorder other than LAL-D that explained the abnormalities and, in the
      5 remaining children, ALT and lipid levels normalized spontaneously, thus
      excluding LAL-D. CONCLUSIONS: This study shows that retrospective data mining is
      unlikely to yield a significant number of LAL-D cases in children. The screening
      algorithm adjusted for children seems useful and accurate in the selection of
      children for further testing, suggesting it can be applied prospectively,
      although further validation is warranted.

PMID- 30286342
TI  - Keeping active: maintenance of physical activity after exercise programmes for
      older adults.
AB  - OBJECTIVES: To explore factors associated with maintenance of moderate-to
      vigorous physical activity (MVPA) in community-dwelling adults aged >=65 years
      after completing a 24-week exercise programme. STUDY DESIGN: This is a cohort
      study nested within a randomised controlled trial evaluating group- and home
      based exercise programmes for older people in England. METHODS: MVPA levels and
      factors potentially associated with physical activity (PA) were self-reported at
      recruitment, 6, 12, 18 and 24 months after exercise programme. Multilevel
      logistic regression estimated odds ratios (ORs) for achieving target MVPA level
      (150 min/week) 6-24 months after exercise programmes ended. RESULTS: Older people
      (OR per year increase: 0.89, 95% confidence interval [CI] 0.86, 0.93) and women
      (OR 0.47, 95% CI 0.33, 0.67) were less likely to achieve target MVPA. Those
      physically active at recruitment (OR 11.28, 95% CI 7.95, 16.01), with wider
      social networks (OR per unit increase in Lubben Social Network Scale: 1.06, 95%
      CI 1.03, 1.10) and performing more sit-to-stands in 30 s (OR for quartile 3
      compared with quartile 1: 1.87, 95% CI 1.12, 3.10), were more likely to achieve
      target MVPA. Negative exercise expectations increased the odds of achieving
      target MVPA but only among the less active at recruitment (OR per unit increase
      in Outcome and Expectation for Exercise negative subscale: 1.90, 95% CI 1.39,
      2.60). Associations did not differ significantly across the follow-up period.
      CONCLUSION: A range of factors are associated with maintenance of PA 6-24 months
      after exercise programmes. Factors are not more strongly associated with shorter
      vs longer term PA maintenance. Commissioners and providers should consider
      targeting maintenance interventions to those least likely to maintain PA.

PMID- 30286344
TI  - Overview of microbes based fabricated biogenic nanoparticles for water and
      wastewater treatment.
AB  - Treatment of toxic and emerging pollutants (T&EPs) is increasing the threats to
      the survival of conventional wastewater treatment (WWTs) technologies. The high
      installation and operational costs of advanced treatment technologies have
      shifted the research interest to the development of economical and reliable
      technology for management of T&EPs. Thus, recently biogenic nanoparticles (BNPs)
      fabricated using microbes/microorganisms are getting tremendous research interest
      due to their unique properties (i.e. high specific surface area, desired
      morphology, catalytic reactivity) for the biodegradation and biosorption of
      T&EPs. In addition, BNPs can be manufactured using metal contaminated water which
      indicates a hidden potential for resource recovery and utilization. Therefore,
      the present study discusses the adsorptive and catalytic performance of BNPs in
      the removal of T&EPs from water (W) and wastewater (WW). In addition, inspired by
      the superior performance of BNPs in advance WWT, a model of BNPs based WWT
      resource recovery and utilization process is also proposed. Finally, main issues
      i.e. mass production, leaching, poisoning/toxicity, regeneration, reusability and
      fabrication costs and process optimization are discussed which are main hinders
      in the transfer of BNPs based WWT technologies from laboratory to commercial
      scale.

PMID- 30286345
TI  - Microwave (MW) remediation of hydrocarbon contaminated soil using spent graphite 
      An approach for waste as a resource.
AB  - In this study, we have explored the possibility of using an industrial waste for
      remediation of heavy fuel oil contaminated soil. Microwave (MW) heating in the
      presence of spent graphite (SG) from an auto forging industry has been used for
      the remediation. The physico-chemical characterization of SG and contaminated
      soil were done. Microwave remediation experiments were conducted in a lab scale
      unit and the effect of different parameters like microwave power, susceptor
      loading and treatment time were studied and optimized. The contaminated and
      decontaminated soils were analysed using GC-MS for total petroleum hydrocarbons
      (TPH), Total Organic Carbon and CHNS analyzers. Batch experiments of soil
      remediation showed that the TPH removal efficiencies (%) of 41.25, 87.77 and
      91.18 at 300, 450 and 600 W respectively at SG concentration of 2.5 (wt. %) for a
      reaction time of 60 min. The addition of SG as susceptor enhanced the desorption
      of long chain hydrocarbons (C12-C29) present in the soil. Desorption of
      hydrocarbons from the soil fits well with first order kinetic model. This study
      successfully demonstrated the reuse of spent graphite (a lubricant waste)
      recovered from metal forging operations for remediating the fuel oil contaminated
      soil.

PMID- 30286346
TI  - Sampling methods and approaches to inform standardized detection of marine alien
      fouling species on recreational vessels.
AB  - Recreational vessels are important contributors to the spread of marine alien
      species, particularly in relation to secondary spread within novel regions. As
      such, these vessels should be considered a monitoring priority. The aim of this
      study was to identify a preferred method for monitoring recreational vessels for
      alien species, while simultaneously developing a framework that enables managers
      to objectively choose the most effective sampling approach given their financial
      constraints. Divers and a remotely operated vehicle (ROV) were considered in
      relation to four sampling approaches i.e. meanders, transects, inspection of
      niche areas and the collection of quadrats. Each was applied to the same 53
      vessels which represented a spectrum of hull fouling cover. The most effective
      methods were diver scrape quadrats (Range of alien species numbers per quadrat: 0
      9, Total alien species: 20) and inspections of niche areas (Range of alien
      species numbers: 0-5, Total alien species: 9). All methods employed using an ROV
      had low efficacy and incurred high costs. While scrape samples were one of the
      most expensive methods, this was offset by the lowest cost per species detected.
      Thus, it is recommended that monitoring programmes utilize scrape samples and
      niche area inspections, but when faced with financial constraints, diver meanders
      and niche inspections offer sound alternatives for detecting alien species.

PMID- 30286348
TI  - A biodegradable biomass-based polymeric composite for slow release and water
      retention.
AB  - Slow-release fertilizer has been proven to be more effective than traditional
      fertilizer for providing a long-term stable nutrient supply. Although such
      fertilizers have been widely investigated, their water-retention properties and
      biodegradability have not been fully analysed. Composites of fertilizers and
      polymers provide opportunities to prepare new types of fertilizer with enhanced
      properties for real applications. Chicken feather protein-graft-poly(potassium
      acrylate)-polyvinyl alcohol semi-interpenetrating networks forming a super
      absorbent resin combined with nitrogen (N) and phosphorus (P) (CFP-g-PKA/PVA/NP
      semi-IPNs SAR) was prepared. The chemically bonded or physically embedded
      fertilizer compound could be released form the resin matrix to the surrounding
      soil under irrigation. The synthesis mechanism, morphology, and chemical and
      mechanical structure of the synthesized composites were investigated. The
      reactant doses were optimized through response surface methodology (RSM). A 30
      day field trial of the prepared SAR was applied to detect the influence of sample
      particle size, soil salinity, pH, and moisture content on the slow-release
      behaviour of N and P. The maximum release values of N and P from the composites
      were 69.46% N and 65.23% P. A 120-day soil burying experiment and 30-day
      Aspergillus niger (A. niger) inoculation were performed, and the biodegradability
      and change in microstructure were monitored. The addition of SAR to soil could
      also improve the water-retention ability of the soil.

PMID- 30286347
TI  - Normative influences: How socio-cultural and industrial norms influence the
      adoption of sustainability practices. A grounded theory of Cretan, small tourism
      firms.
AB  - Previous research explains the various factors that motivate or discourage the
      owner-managers of small firms to behave sustainably. However, it has failed to
      develop a meaningful understanding of how these factors inter-relate or combine
      to influence their decisions. This research identifies and explains how socio
      cultural and industrial norms influence the intentions and behaviours towards
      sustainability of owner-managers of small tourism firms. This grounded theory
      study shows how selective peer association allows the use of norms that match
      one's values to predict the difficulties, benefits and therefore justification
      for pro-sustainability (in)action. Locally-held socio-cultural norms determine
      what is commonly (dis)approved of through reflective and comparative processes.
      Connectedness to the locality triggers empathy for nature and the local society,
      but not a corresponding sense of responsibility. This dissonance is managed by
      allocating responsibility to industry actors perceived as more powerful,
      particularly tour operators and consumers, and to the widespread greed and short
      term culture dominating the sector.

PMID- 30286349
TI  - Facile synthesis of graphene oxide-silver nanocomposite for decontamination of
      water from multiple pollutants by adsorption, catalysis and antibacterial
      activity.
AB  - Here in, we presented a facile one-step method for the synthesis of Graphene
      oxide-silver (GO-Ag) nanocomposite and its applications as a sorbent for the
      elimination of some toxic pollutants from aqueous medium, as an efficient
      catalyst in the individual as well as simultaneous reduction reactions of
      multiple compounds, and as an antibacterial agent for the destruction of some
      harmful microorganisms existent in wastewater. GO was prepared using a modified
      Hummers method and Ag nanoparticles were integrated on GO sheets by chemical
      reduction of Ag+ ions on the surfaces of GO sheets. The composition and
      morphology of the nanocomposite was extensively characterized with elemental
      dispersive X-ray analysis (EDX), Fourier transform infra-red (FT-IR)
      spectroscopy, transmission electron microscopy (TEM), field emission scanning
      electron microscopy (FESEM), X-ray diffraction (XRD), and thermal gravimetric
      analysis (TGA). The GO-Ag nanocomposite demonstrated remarkable adsorption
      capacities and recyclability for malachite green (MG) and ethyl violet (EV) dyes.
      Various experimental parameters affecting adsorptive behavior of nanocomposite
      like temperature, pH, time of contact between dye and adsorbent, and adsorbent
      dose were evaluated thoroughly. Experimental data was simulated with different
      adsorption isotherms and kinetic models to evaluate adsorption behavior of both
      dyes and results confirmed the adsorption of both the dyes to be followed by
      pseudo 2nd order kinetic model and Langmuir adsorption model. Moreover, adsorbent
      was regenerated in suitable media for both dyes without any loss in removal
      efficiency. The catalytic performance for the 2-nitroaniline (2-NA) reduction was
      investigated in detail. Most importantly, the prepared nanocomposite was found to
      have potential to adsorb multiple pollutants all together as well as to catalyze
      the simultaneous reduction of a mixture of dyes (MG, MO, and EV) and 2-NA. An
      additional advantage of the GO-Ag nanocomposite was its antibacterial activity
      acquired to the presence of Ag nanoparticles. Two bacterial strains (Gram
      negative bacterium, E. coli and the Gram-positive bacterium, S. aureus) were used
      to test antibacterial activity of composite and the results confirmed the
      remarkable performance of the nanocomposite in destroying harmful pathogens.

PMID- 30286350
TI  - Microalgae and bacteria dynamics in high rate algal ponds based on modelling
      results: Long-term application of BIO_ALGAE model.
AB  - The mechanistic model (BIO_ALGAE) for microalgae-bacteria based wastewater
      treatment systems simulation was validated in the long-term (months) using
      experimental results from a pilot high rate algal pond (HRAP) treating municipal
      wastewater. Simulated results were compared with data gathered during two
      different seasons (summer and winter), and with the HRAP operating at different
      hydraulic retention times (HRT, 4 and 8 days, respectively). The model was able
      to simulate with a good degree of accuracy the dynamics of different components
      in the pond, including the total biomass (bacteria and microalgae). By means of
      practical study cases, the influences of different HRT operating strategies and
      seasonal variations of temperature and irradiance were investigated for the
      relative proportion of microalgae and bacteria, and biomass production over a
      year cycle. Model predictions show that the proportion of microalgae in the
      microalgal/bacterial biomass is quite similar in warmer months if the pond is
      operated with 8-day HRT (76-78%) or 4-day HRT (60-75%). Significant differences
      were observed in colder months (4-day HRT (27-33%) and 8-day HRT (65-68%)). The
      model identified a scenario in which overall microalgae production and ammonium
      removal efficiency were optimized. By operating the HRAP with lower HRT (4 days)
      in warmer months and higher HRT (8 days) in colder months, the average annual
      microalgae production increased up to 14.1 gTSS m-2d-1, in contrast with 10.2
      gTSS m-2d-1 and 9.2 gTSS m-2d-1 operating with constant HRAP (4 and 8 days,
      respectively) over a year cycle.

PMID- 30286351
TI  - Factors controlling sediment and nutrient fluxes in a small microtidal salt marsh
      within the Venice Lagoon.
AB  - Coastal salt marshes are among the Earth's most productive ecosystems and provide
      a number of ecosystem services. Water quality regulation by storing, transforming
      and releasing nutrients, organic matter and suspended sediment is recognized as
      one of the most important functions of salt marshes. The self-purification
      capacity of intertidal ecosystems contributes to mitigating nutrient inputs,
      acting as a buffer zone between watersheds and coastal waters, especially in
      relation to climate change and the increasing frequency of impulsive extreme
      events. Understanding sediment and nutrient fluxes and assessing the mechanisms
      that control them are valuable for the preservation and future restoration of
      salt marshes and for enhancing their effectiveness in providing water quality
      regulation services. To investigate the main driving factors in microtidal
      environments, changes in suspended sediment and nutrient concentrations were
      measured during several tidal cycles in a small microtidal reconstructed salt
      marsh in the Venice Lagoon, which was selected as the experimental site. The
      tidal amplitude, nutrients and total suspended solid concentrations were measured
      during 6 tidal cycles between September 2011 and October 2013. The water
      discharge was derived by forcing the hydrodynamic MIKE-DHI numerical model with
      the measured tidal levels. Fluxes were assessed by coupling field data with the
      calculated discharges. The salt marsh filtering function was related to the
      inflow matter concentrations and tidal amplitude. When high suspended solid and
      nutrient concentrations enter the salt marsh, accumulation processes prevail on
      release. In contrast, in the case of low concentrations and high tidal excursion,
      the salt marsh functions as a nutrient and sediment source. During all campaigns,
      the nitrogen removal function was more effective within the intertidal vegetated
      areas. Sediment release was the dominant process in the outermost creek, whereas
      sedimentation prevailed in the inner area of the salt marsh because of the
      attenuation of hydrodynamic forcing during tide propagation.

PMID- 30286352
TI  - Characterization of vertical distribution and radiative forcing of ambient
      aerosol over the Yangtze River Delta during 2013-2015.
AB  - As the central part of eastern China, the Yangtze River Delta (YRD) region, with
      its rapid economic growth and industrial expansion, has experienced severe air
      quality issues. In this study, the monthly variation and interaction between
      aerosol direct radiative forcing (ADRF) and aerosol vertical structure during
      2013-2015 over the YRD were investigated using ground-based observations from a
      Micro Pulse Lidar (MPL) and a CE-318 sun-photometer. Combining satellite products
      from MODIS and CALIPSO, and reanalysis wind fields, an integrated discussion of a
      biomass burning episode in Hangzhou during August 2015 was conducted by applying
      analysis of optical properties, planetary boundary layer (PBL), spatial-temporal
      and vertical distributions, backward trajectories, Potential Source Contribution
      Function (PSCF), and Concentration Weighted Trajectory (CWT). The results reveal
      that a shallower PBL coincides with higher scattering extinction at low altitude,
      resulting in less heating to the atmosphere and radiative forcing to the surface,
      which in turn further depresses the PBL. In months with a deeper PBL, the
      extinction coefficient decreases rapidly with altitude, showing stronger
      atmospheric heating effects and ADRF to the surface, facilitating the turbulence
      and vertical diffusion of aerosol particles, which further reduces the extinction
      and raises the PBL. Because of the hygroscopic growth facilitated by high
      relative humidity, June stands out for its high scattering extinction coefficient
      and relatively low PBL, and the reduced ADRF at the surface and the enhanced
      cooling effect on near-surface layer in turn depresses the PBL. Absorptive
      aerosols transported from biomass burning events located in Zhejiang, Jiangxi,
      and Taiwan provinces at 1.5 km, result in high ADRF efficiency for atmospheric
      heating. And the enhanced heating effect on near-surface layer caused by
      absorptive particles facilitates PBL development in August over the YRD.

PMID- 30286353
TI  - Assessing climate change impacts on stream temperature in the Athabasca River
      Basin using SWAT equilibrium temperature model and its potential impacts on
      stream ecosystem.
AB  - Stream temperatures, which influence dynamics and distributions of the aquatic
      species and kinetics of biochemical reactions, are expected to be altered by the
      climate change. Therefore, predicting the impacts of climate change on stream
      temperature is helpful for integrated water resources management. In this study,
      our previously developed Soil and Water Assessment Tool (SWAT) equilibrium
      temperature model, which considers both the impacts of meteorological condition
      and hydrological processes, was used to assess the climate change impact on the
      stream temperature regimes in the Athabasca River Basin (ARB), a cold climate
      region watershed of western Canada. The streamflow and stream temperatures were
      calibrated and validated first in the baseline period, using multi-site observed
      data in the ARB. Then, climate change impact assessments were conducted based on
      three climate models under the Representative Concentration Pathways 4.6 and 8.5
      scenarios. Results showed that warmer and wetter future condition would prevail
      in the ARB. As a result, streamflow in the basin would increase despite the
      projected increases in evapotranspiration due to warmer condition. On the basin
      scale, annual stream temperatures are expected to increase by 0.8 to 1.1  degrees
      C in mid-century and by 1.6 to 3.1  degrees C in late century. Moreover, the
      stream temperature changes showed a marked temporal pattern with the highest
      increases (2.0 to 7.4  degrees C) in summer. The increasing stream temperatures
      would affect water quality dynamics in the ARB by decreasing dissolved oxygen
      concentrations and increasing biochemical reaction rates in the streams. Such
      spatial-temporal changes in stream temperature regimes in future period would
      also affect aquatic species, thus require appropriate management measures to
      attenuate the impacts.

PMID- 30286354
TI  - Effect of metabolic uncoupler, 2,4-dinitrophenol (DNP) on sludge properties and
      fouling potential in ultrafiltration membrane process.
AB  - Energy uncoupling technology was applied to the membrane process to control the
      problem of bio-fouling. Different dosages of uncoupler (2,4-dinitrophenol, DNP)
      were added to the activated sludge, and a short-term ultrafiltration test was
      systematically investigated for analyzing membrane fouling potential and
      underlying mechanisms. Ultrafiltration membrane was used and made of polyether
      sulfone with a molecular weight cut off (MWCO) of 150 kDa. Results indicated that
      low DNP concentration (15-30 mg/g VSS) aggravated membrane fouling because more
      soluble microbial products were released and then rejected by the membrane, which
      significantly increased cake layer resistance compared with the control.
      Conversely, a high dosage of DNP (45 mg/g VSS) retarded membrane fouling owing to
      the high inhibition of extracellular polymeric substances (proteins and
      polysaccharides) of the sludge, which effectively prevented the formation of cake
      layer on the membrane surface. Furthermore, analyses of fouling model revealed
      that a high dosage of DNP delayed the fouling model from pore blocking transition
      to cake filtration, whereas this transition process was accelerated in the low
      dosage scenario.

PMID- 30286355
TI  - Preliminary study of long-range transport of halogenated flame retardants using
      Antarctic marine mammals.
AB  - Eight PBDE congeners, three emerging brominated flame retardants, five
      dechloranes and eight MeO-PBDEs were monitored in tissues (muscular, adipose,
      brain) and fur of southern elephant seal and Antarctic fur seal of the South
      Shetland Islands, Antarctic Peninsula. Total PBDEs and total dechloranes
      concentrations ranged between n.d.-6 ng/g lw. While PBDEs were not detected in
      brain tissue, Dec 602 was found in brain tissue of both seal species indicating
      that dechloranes -with potential neurological toxicity- could cross the blood
      brain barrier. Emerging brominated flame retardants were not detected in any
      sample and only two MeO-PBDEs, which are of natural origin, were found. The
      presence of the detected compounds in biota from the Antarctic evidences their
      long-range transportation, being of special interest the detection of emerging
      compounds such as dechloranes. This is the first time that these contaminants
      have been detected in marine mammals from the Antarctic. BDE-47 concentrations
      were lower than previously reported for the same species, suggesting a successful
      effect of the existing regulation and bans on PBDEs. CAPSULE ABSTRACT:
      Halogenated flame retardants were in tissues of Antarctic seals proving long
      range transport. Dechloranes showed similar behaviour to PBDEs, additionally they
      crossed the BBB.

PMID- 30286356
TI  - Ecosystem-based management planning across aquatic realms at the Ria de Aveiro
      Natura 2000 territory.
AB  - Ria de Aveiro represents a coastal territory, in which its natural capital,
      mostly classified under a Natura 2000 network of protected areas, is of paramount
      importance for the regional and national economy, supporting harbour activities
      and maritime traffic, agriculture, commercial fisheries, aquaculture,
      manufacturing, tourism, sports and recreational activities. Current and foreseen
      changes connected to human activities, namely land and water uses and potential
      conflicts, in frame of environmental policies, sustainable economic development
      and human well-being require the implementation of ecosystem-based management
      (EBM) planning processes considering the connectivity across marine,
      transitional, freshwater, and terrestrial domains. The main objective is to
      elaborate on the co-development of the EBM planning process across the three
      water domains, all characterized by high biodiversity and by the wide range of
      services provided by ecosystems and their abiotic components, for the mitigation
      of impacts from the management plan under implementation. The approach used
      follows a stepwise procedure in frame of resilience principles, considering the
      analysis of the relationship between the social and ecological components and on
      how these can be connected through risk assessment and a spatial multi-criteria
      analysis based on the delivery of ecosystem services. Stakeholders' perception
      matched the ecosystem services provisioning risk assessment and supported the
      planning EBM response that consist in saltmarshes and seagrasses meadows
      restoration programs. Compliance of the proposed measures is achievable regarding
      policies (policy targets and policy instruments) and feasibility (scientific and
      technological knowledge and financial resources). The EBM response can support
      the Vouga estuary management plan and regional smart specialization (RIS3
      Centro).

PMID- 30286357
TI  - Microplastics in the Northwestern Pacific: Abundance, distribution, and
      characteristics.
AB  - Prevalence of microplastics (MPs) throughout the world's oceans has raised
      growing concerns due to its detrimental effects on the environment and living
      organisms. Most recent studies of MPs, however, have focused on the estuaries and
      coastal regions. There is a lack of study of MPs pollution in the open ocean. In
      the present study, we conducted field observations to investigate the abundance,
      spatial distribution, and characteristics (composite, size, color, shape and
      surface morphology) of MPs at the surface of the Northwestern Pacific Ocean.
      Samples of MPs were collected at 18 field stations in the Northwestern Pacific
      Ocean using a surface manta trawl with a mesh size of ~330 MUm and width of 1 m
      from August 25 to September 26, 2017. The MPs were characterized using light
      microscopy, Micro-Raman spectroscopy, and scanning electron microscopy (SEM). Our
      field survey results indicate the ubiquity of MPs at all stations with an
      abundance from 6.4 * 102 items km-2 to 4.2 * 104 items km-2 and an average
      abundance of 1.0 * 104 items km-2. The Micro-Raman spectroscopic analysis of the
      MPs samples collected during our field survey indicates that the dominant MPs is
      polyethylene (57.8%), followed by polypropylene (36.0%) and nylon (3.4%). The
      individual chemical compositions of MPs from the stations within the latitude
      range 123-146 degrees E are comparable with each other, with PE being the
      dominating composition. Similar chemical fingerprints were observed at these
      field stations, suggesting that the MPs originated from similar sources. In
      contrast, the major MPs at the field stations adjacent to Japan is polypropylene,
      which may originate from the nearby land along the coast of Japan. Physical
      oceanography parameters were also collected at these stations. The spatial
      distribution of MPs is largely attributed to the combined effects of flow
      pattern, adjacent ocean circulation eddies, the Kuroshio and Kuroshio Extension
      system.

PMID- 30286358
TI  - Non-native freshwater fauna in Portugal: A review.
AB  - We present the most updated list of non-native freshwater fauna established in
      Portugal, including the Azores and Madeira archipelagos. This list includes 67
      species at national level but corresponds to 84 species records, of which 53 are
      in the mainland, 23 in the Azores and 8 in Madeira archipelagos. We also discuss
      the progression of the cumulative number of introductions since 1800 and identify
      the most probable vectors of introduction, main taxonomic groups and their
      regions of origin. Furthermore, we review the existing knowledge about ecological
      and economic impacts, invasion risk and potential distribution of invaders, under
      present and future climatic conditions, and the applied management actions,
      including the production of legislation. Along the 20th century the number of
      successful introductions increased at an approximate rate of two new species per
      decade until the beginning of 1970s. Since then, this rate increased to about 14
      new species per decade. These introductions were mainly a result of fisheries, as
      contaminants or for ornamental purposes. Fish and mollusks are the taxonomic
      groups with more established species, representing more than half of the total.
      Most species (>70%) are native from other regions of Europe and North America.
      Studies about ecological or socioeconomic impacts are more common for fish,
      crustaceans and mollusks. Impacts for most amphibians, reptiles and mammals are
      not thoroughly studied. A few studies on the impacts and management actions of
      health-threatening mosquitoes are also available. The potential distribution in
      the Portuguese territory was modelled for 26 species. Only a minority of these
      models provides projections of distributions under scenarios of future climate
      change. A comparison of the Portuguese and EU legislation shows large
      discrepancies in the invasive species lists. Using the EU list and a ranking
      procedure for the national context, we identify freshwater species of high
      national concern for which actions are urgently needed.

PMID- 30286359
TI  - The impact of socio-economic development and climate change on E. coli loads and
      concentrations in Kabul River, Pakistan.
AB  - Microbial pollution is a major problem worldwide. High concentrations of
      Escherichia coli have been found in Kabul River in Pakistan. E. coli
      concentrations vary under different socio-economic conditions, such as population
      and livestock densities, urbanisation, sanitation and treatment of wastewater and
      manure, and climate-change aspects, such as floods and droughts. In this paper,
      we assess potential future E. coli loads and concentrations in the Kabul River
      using the Soil and Water Assessment Tool with scenarios that are based on the
      most recent Shared Socio-economic Pathways and Representative Concentration
      Pathways (SSPs and RCPs) developed for the Intergovernmental Panel on Climate
      Change (IPCC). Scenario_1 considers moderate population and livestock density
      growth, planned urbanisation and strongly improved wastewater and manure
      treatment (based on SSP1, "Sustainability"), and moderate climate change (RCP4.5,
      moderate greenhouse gas (GHG) emissions). Scenario_2 considers strong population
      and livestock density growth, moderate urbanisation, slightly improved wastewater
      treatment, no manure treatment (based on SSP3, "Regional rivalry") and strong
      climate change (RCP8.5, high GHG emissions). Simulated E. coli responses to
      Scenario_2 suggest a mid-century increase in loads by 111% and a late century
      increase of 201% compared to baseline loads. Similarly, simulated E. coli loads
      are reduced by 60% for the mid-century and 78% for the late century compared to
      the baseline loads. When additional treatment is simulated in Scenario_1, the
      loads are reduced even further by 94%, 92% and 99.3% compared to the baseline
      concentrations when additional tertiary treatment, manure treatment or both have
      been applied respectively. This study is one of the first to apply combined socio
      economic development and climate change scenario analysis with an E. coli
      concentration model to better understand how these concentrations may change in
      the future. The scenario analysis shows that reducing E. coli concentrations in
      Pakistan's rivers is possible, but requires strongly improved waste water
      treatment and manure management measures.

PMID- 30286360
TI  - A modeling study of the peroxyacetyl nitrate (PAN) during a wintertime haze event
      in Beijing, China.
AB  - Peroxyacetyl nitrate (PAN), as the second most important photochemical pollutant,
      could threaten human health and terrestrial ecosystem. Observed high PAN
      concentrations in wintertime in Beijing are comparable to those in summertime
      when photochemistry is strong. In this study, we investigated the variations of
      concentrations of PAN and other related chemical species during a haze event on
      February 13-16, 2017 in Beijing using a combination of in-situ observations and
      the WRF-Chem model simulation. During this episode, the observed mean (maximum)
      PAN concentrations at the urban and rural sites were 1.9 (4.7) ppb and 1.8 (4.3)
      ppb, respectively. Model evaluation showed that the simulation with CBM-Z gas
      phase scheme performed much better than simulation using the RADM2 scheme, which
      mainly results from the accurate representation of the reaction rates for PAN
      formation through CH3C(O)O2 radicals and NO2 in the CBM-Z scheme. But simulated
      PAN concentrations in Beijing were still underpredicted using the CBM-Z scheme,
      likely due to the underestimation of VOC emissions. Since the lifetime of PAN
      becomes as long as several days in wintertime due to lower temperature, it could
      be conducive to be accumulated and transported. Sensitivity simulation
      demonstrated that local sources accounted for about 15%-30% of mean PAN
      concentrations over most of Beijing during the event, lower than that of PM2.5
      (25%-60%). These suggest that during Beijing wintertime polluted days, increased
      PAN concentration, which is dominantly contributed by regional transport from
      surrounding areas, will cause more health concerns, and its control strategies
      need larger regional efforts than those conducted for PM2.5.

PMID- 30286361
TI  - DNA analysis of hairs in a suspected case of child abuse.
AB  - Hairs are often used for DNA analysis in criminal investigations. DNA analysis of
      hairs with root sheaths is easy in many cases, but analyses using only the shaft
      or tip of the hair are often difficult. Here we describe a suspected case of
      child abuse in which we were commissioned to perform DNA analysis. Among 100
      hairs, PCR amplification was succeeded in 99 samples, and as a result of direct
      sequencing, mitochondrial DNA (mtDNA) of the 99 hairs were classified into 6
      types. The most common type was the 8-base substitution type of 16,168T-16,172C
      16,183C-16,189C-16,217C-16,249C-16,325C-16,390A, which was observed in 86 hairs.
      This corresponded to the type of the victim. Total 736 STRs (75.5%) in 975 loci
      of 65 hairs could be typed, and only an amelogenin locus was typed in another
      hair. All 15 loci were typed in 10 hairs. STR types of 65 (98.5%) in 66 hairs
      were consistent with that of the victim. From 10 naturally-shed hair of a person,
      only 37 STRs (30.8%) in 120 loci of 8 hairs were typed, and all 15 loci could not
      be typed in these hairs. This difference in success rates of STR analysis
      suggested strongly that the hairs in this case were not shed naturally but
      forcibly, and the relevance to child abuse was suspected.

PMID- 30286362
TI  - Intralipid(r) may represent a new hope for patients with reproductive failures
      and simultaneously an over-immune endometrial activation.
AB  - PROBLEM: Continuous failures to achieve a pregnancy despite effective embryo
      transfers is extremely distressing for couples. In consequence, many adjuvant
      therapies to IVF have been proposed to achieve an "ideal" immune environment. We
      here focus on Intralipid(r) therapy (IL) reported to have immunosuppressive
      properties on NK cells. METHOD OF STUDY: 94 patients exhibited an immune profile
      of endometrial over-immune activation and an history of repeated implantation
      failures despite multiple embryos transfers (RIF). They received a slow perfusion
      of Intralipid(r). We here report the live birth rate following the procedure at
      the next embryo transfer. To get new insight on its mechanism of action, a second
      immune profiling had been performed under Intralipid(r) before the embryo
      transfer. RESULTS: The live birth rate of the RIF cohort treated with
      Intralipid(r) reached 54% (51/94) at the next embryo transfer. In patients
      successfully pregnant under Intralipid(r) who benefitted of a test of sensibility
      before the embryo transfer, we observed a significant decrease of the three
      biomarkers used to diagnose the over-immune endometrial activation (CD56 cells;
      IL-18/TWEAK, IL-14/FN-14). CONCLUSIONS: Double blind placebo versus Intralipid(r)
      studies should be conducted. Intralipid(r) may be an option to explore in RIF
      patients who exhibit an over-immune activation of uNK cells.

PMID- 30286363
TI  - TVT Abbrevo and Miniarc suburethral sling in women with stress urinary
      incontinence - A randomised controlled trial.
AB  - INTRODUCTION: Single incision slings (SIS) were introduced in an attempt to
      decrease the complications associated with retropubic and transobturator slings.
      The TVT Abbrevo is a modification of the TVT-O with a reduced length and less
      immediate postoperative pain. The Miniarc SIS has been shown to be equivalent to
      outside-in transobturator sling, Monarc at 12 month follow-up. OBJECTIVE: To
      evaluate objective and subjective outcomes of MiniArc SIS and TVT Abbrevo
      midurethral sling (MUS) in women with stress urinary incontinence. METHODS:
      Female subjects who were assessed and referred for stress urinary incontinence
      surgery were eligible to participate in this study. Exclusion criteria included
      women with intrinsic sphincter deficiency previous failed midurethral or fascial
      sling, untreated detrusor overactivity or significant voiding dysfunction.
      Patients' randomisation was performed with computer-generated blocks of 4-8, with
      concealed allocation. Assuming an objective cure rate of 90% for TVT
      AbbrevoTMwith a power of 80%, a sample size of 79 in each arm was required to
      detect a clinical difference of 15%, using a one sided alpha of 0.05. The target
      recruitment number was 220 allowing for an attrition rate of 15%. Institution
      ethics approval (11261B) was obtained and the trial was registered with the
      Australian New Zealand Clinical Trials Registry (ACTRN12611001151921). Routine
      preoperative assessment was conducted for objective data, whilst patient reported
      outcome tools (PRO) were utilised for subjective outcomes. These include ICIQ UI
      SF, ICIQ OAB, IIQ7, EQ5D, PISQ12, PGIs & PGII. TVT AbbrevoTM or MiniarcTMwere
      performed in a standardized fashion, together with any concomitant prolapse
      surgery. Review was conducted at 6 weeks and at 6 and 12 months. Objective cure
      was defined as a negative cough stress test with a comfortably full bladder.
      Subjective cure was defined as no report of leakage with physical exertion. All
      Data was collected and outcomes were analysed statistically. RESULTS: Between
      February 2011 and January 2016,a total of 246 women were randomized to receive
      MiniArc (121) or TVT Abbrevo (125). Baseline characteristics were clinically
      balanced in both groups. At 6 months subjective (94.4% vs 95.7% p=0.74) and
      Objective (92.9% vs 95.9% p=0.49) cure rates were high and not statistically
      different. At 12 months there were also no differences in subjective (73.6% vs
      76.9% p=0.73) or objective (90.5% vs 96.0% p=0.21) cure rates. No differences
      were found in functional outcomes or when adjusted for potential confounding
      factors such as age, parity, BMI or menopausal status. CONCLUSION: We found no
      significant differences in subjective and objective cure rates at 6 and 12months
      between MiniArc and TVT Abbrevo.

PMID- 30286364
TI  - MELF pattern of myometrial invasion and role in possible endometrial cancer
      diagnostic pathway: A systematic review of the literature.
AB  - Microcystic, elongated, fragmented (MELF) pattern of myometrial invasion has been
      proposed as a prognostic marker in patients with endometrial carcinoma (EC). Its
      prognostic and predictive effect still remains elusive. The aim of the present
      study is to accumulate the current knowledge on the role of MELF pattern in the
      prognosis and survival of patients with EC. Medline, Scopus, Google Scholar, and
      Clinicaltrials.gov databases were searched for articles published up to May 2018,
      along with the references of all articles. Prospective and retrospective trials
      reporting outcomes of cases with EC who were examined for MELF pattern were
      considered eligible for inclusion in the present systematic review. Of the 196
      records screened, 14 were considered eligible. A total of 14 studies which
      comprised 588 women were finally included in the present systematic review. All
      the included patients were evaluated for presence of MELF pattern of myometrial
      invasion. MELF positive (+) patients were more likely to present with larger and
      higher grade tumors, lymph node metastasis, lymphovascular invasion and >50%
      myometrial invasion. No difference was reported in disease free survival (DFS)
      and disease specific survival (DSS) as well as in vaginal recurrence rates. MELF
      (+) was reported as a significant indicator of survival. In conclusion, MELF
      pattern of myometrial invasion plays a critical role in lymphovascular space
      invasion and lymph node metastasis in patients with EC. Regardless, its
      implication in survival and recurrences is ill determined.

PMID- 30286365
TI  - 2D USS of the pelvic floor in the 3rd trimester versus mode of delivery.
AB  - OBJECTIVE: Biomechanics of pelvic floor muscles is becoming an important field of
      research in understanding a complex process of labour. Current evidence indicates
      that the levator ani stretches to allow passage of the fetus through the birth
      canal. We sought to identify properties of the functional female pelvic floor
      during pregnancy that could help to predict the mode of delivery, especially in
      women who underwent caesarean section in the past. METHODS: A single centre
      prospective cohort study of pregnant women in the 3rd trimester attending
      antenatal clinic. Participants were categorised into three groups: 1.
      nulliparous, 2. previous one vaginal delivery and 3. previous one caesarean
      section who chose a trial of labour in their current pregnancy. All women
      underwent ultrasonographic evaluation of their pelvic floor muscles.
      Distensibility and the mode of delivery were assessed in participants' current
      pregnancies. The primary outcome was the mode of delivery. ANOVA test was used
      for statistical analysis. RESULTS: 133 women were included: 55 nulliparous, 52
      primiparous (previous one vaginal birth), and 26 primiparous (previous one LSCS
      and planned for vaginal delivery after caesarean (VBAC)). Participants were
      scanned at an average gestation of 32 weeks. The inter-observer reliability test
      for puborectalis distensibility was good (kappa 0.75). Overall, women who
      delivered vaginally had a more distensible puborectalis muscle than those who
      delivered by emergency LSCS regardless of their previous type of delivery. Women
      who underwent a successful VBAC had less distensible pelvic floor muscles
      compared to their nulliparous and primiparous counterparts (who delivered
      vaginally in the past). CONCLUSION: These results support our basic conceptual
      theory of puborectalis muscle distensibility influencing the mode of delivery and
      endorse application of dynamic pelvic floor ultrasound in future studies. We
      identified measurable differences in the functional female pelvic anatomy aiding
      a better understanding of physiology of the labour. There are trends towards
      lesser distensibility in women who delivered by LSCS.

PMID- 30286366
TI  - An investigation of associations between experience of childhood trauma and
      political violence and theory of mind impairments in schizophrenia.
AB  - There has been little examination of the association between trauma and cognitive
      deficits seen in individuals diagnosed with schizophrenia. Theory of Mind (ToM)
      impairments are a significant feature of schizophrenia but it remains unclear as
      to why these deficits are so prevalent in this population. This study aimed to
      explore associations between ToM deficits and specific forms of childhood
      adversities in a schizophrenia population. The study sample comprised of 66
      adults with a confirmed diagnosis of schizophrenia, attending mental health
      services in Northern Ireland. Assessments were completed to ascertain if
      individuals had prior experience of sexual or physical abuse, emotional neglect
      or experience of the political violence of Northern Ireland's "Troubles", and the
      Gardner Hinting Test was applied to assess ToM ability. Backwards stepwise
      regression analyses demonstrated that emotional neglect, specifically during
      early childhood (0-6 years) predicted ToM impairments in this group. Conflict
      related trauma was also associated with ToM but was not an independent
      significant predictor of ToM deficits. This is the first study to examine links
      between specific forms of childhood adversity and ToM impairments in individuals
      diagnosed with schizophrenia. Potential underpinning psychological mechanisms are
      considered and implications for clinical practice are discussed.

PMID- 30286367
TI  - Stigma and discrimination in individuals with first episode psychosis; one year
      after first contact with psychiatric services.
AB  - Stigma and discrimination in psychotic illness has not been robustly studied in
      those presenting with their first episode of psychosis (FEP). We prospectively
      examined patterns of stigma and discrimination one year after index presentation
      with FEP and correlates with baseline demographic, symptom burden, depression and
      level of functioning. We surveyed 101 subjects using the Discrimination and
      Stigma Scale-12 (DISC-12) and administered the Positive and Negative Syndrome
      Scale (PANSS), Global Assessment of Function (GAF) and the Patient Health
      Questionnaire (PHQ-9).  Discrimination was experienced in 76%; being shunned by
      people because of mental illness, making and keeping friends and from family were
      most affected. Older age, female gender, marital status and a family history of
      mental illness were significantly associated with higher unfair treatment. Higher
      PANSS score at baseline, 3-month and 12-month was significantly associated with
      lower positive treatment, higher stopping self-scores and lower overcoming stigma
      scores, respectively. Higher GAF score at 12-month was associated with higher
      overcoming stigma scores. Lower PHQ-9 scores was significantly correlated with
      overcoming stigma. In conclusion, stigma and discrimination is highly prevalent
      among individuals with FEP; the extent is associated with specific demographic
      variables, symptom burden, presence of depression and level of functioning.
      Limitations include selection bias of subjects, potential underestimation of
      stigma from participants who defaulted or refused to participate and inability to
      establish causality.

PMID- 30286368
TI  - Association on DISC1 SNPs with schizophrenia risk: A meta-analysis.
AB  - Schizophrenia is a major psychiatric disorder with complex genetic,
      environmental, and psychological etiologies. Although DISC1 gene has been shown
      as a risk factor for schizophrenia in some reports, there is a lack of a
      consensus. We therefore performed separate meta-analyses aiming to assess the
      associations between DISC1 SNPs and schizophrenia risk. We found that SNP
      rs821597 is significantly associated with schizophrenia risk in terms of both
      allelic and genotypic distribution, while SNP rs821616 is associated with
      schizophrenia in terms of genotypic distribution, especially in cases above 40
      years old.

PMID- 30286369
TI  - Chinese version of the clinical learning environment comparison survey:
      Assessment of reliability and validity.
AB  - BACKGROUND: Simulation is recommended as a substitute for clinical practice among
      nursing students. No current guidelines exist regarding the accurate percentage
      of simulation hours versus clinical practice hours. Comparing simulation with
      clinical practice is needed so that both strategies can be optimally combined in
      nursing education. The 29-item Clinical Learning Environment Comparison Survey
      (CLECS) is validated to compare the traditional and simulated clinical
      environment in meeting nursing students' learning needs. This type of tool is not
      available in China. OBJECTIVES: This study aimed to translate and test the
      psychometric properties of CLECS for Chinese undergraduate nursing students.
      DESIGN: This is a cross-sectional study. SETTINGS: Two nursing schools in Central
      and East China. PARTICIPANTS: A total of 179 undergraduate nursing students who
      had participated in both traditional and high fidelity simulated clinical
      practice were recruited. METHODS: A standard procedure with forward translation,
      back translation, cultural adaptation and pilot testing was followed to test the
      CLECS (Chinese version). An exploratory factor analysis was used to establish a
      modified factor structure of CLECS (Chinese version); a confirmatory factor
      analysis verified its construct validity. Reliability of the CLECS (Chinese
      version) was estimated using the intraclass correlation coefficients (ICCs) and
      Cronbach's alpha coefficients. RESULTS: The exploratory factor analyses explained
      61.43% and 60.11% of the total variances in traditional and simulated clinical
      environment. The proposed factor solution of the CLECS (Chinese version) obtained
      satisfactory model fit and nesting model between two nursing schools. In the
      proposed model, ICCs were 0.61 and 0.93, and Cronbach's alpha coefficients were
      0.75 and 0.95 in the traditional and simulated clinical environment. CONCLUSIONS:
      The CLECS (Chinese version) showed satisfactory reliability and validity among
      Chinese undergraduate nursing students. Further validation of the CLECS (Chinese
      version) is needed in a more representative and larger sample. The CLECS (Chinese
      version) should be further tested as an effective tool to compare the traditional
      and simulated clinical practice among Chinese nursing schools.

PMID- 30286370
TI  - Mobile persuasive technology for the teaching and learning in surgical safety:
      Content validation.
AB  - BACKGROUND: Patient safety is a fundamental component of high-quality delivery of
      health care. However, despite scientific advances, surgical patients continue to
      face risks. Among the most common complications in surgery are operations on the
      wrong patient, performance of the wrong procedure or operation on the wrong
      surgical site, lack of adequate or required equipment, failure to prevent blood
      loss, and surgical items left inside patients. In this context, the planning and
      development of innovative educational strategies is important for prevention of
      adverse events and the improvement of surgical patient safety culture. OBJECTIVE:
      To describe the process of validating the content of mobile technology for
      education about surgical safety. METHODS: Content validation using the Delphi
      technique was carried out from December 2015 to January 2016 at a Federal
      University in South Brazil. Content development and animations were produced by
      the authors from a verification list for safety surgery and a safety surgery
      protocol. Twelve judges assessed five variables (Content, Language, Illustration,
      Layout and Motivation), for consensus on content validation. They evaluated
      quality of each item, using a rating scale consisting of five levels (1 to 5).
      RESULTS: Two assessment rounds were done, with a mean content validity index
      (CVI) of 0.95 and 1.0 and a kappa index of >0.83 and >0.92, respectively. The
      judges provided positive comments about each phase of the study, most of comments
      highlights were: choice of very relevant subject matter, excellent quality of the
      material and the motivation that the material can provide to the target audience.
      CONCLUSION: The study validated the content of learning technology by general
      consensus of judges with a high level of concordance among evaluated items. The
      application was considered adequate for educating students and health
      professionals about surgical safety.

PMID- 30286371
TI  - Evaluation of training on palliative care for staff working within a homeless
      hostel.
AB  - BACKGROUND: In the UK, many people experiencing homelessness whose health is
      deteriorating remain in homeless hostels due to few suitable alternative places
      of care. Hostel staff struggle to support residents with deteriorating health and
      palliative care services are rarely involved. There is recognition of the need
      for multiagency working to support this group. OBJECTIVES: To pilot and evaluate
      the impact of a two-day training course for hostel staff around supporting
      clients with palliative care needs, and increasing multiagency working. DESIGN:
      Mixed methods evaluation using pre-and-post training data collection. SETTINGS
      AND PARTICIPANTS: Frontline staff from two London homeless hostels. METHODS:
      Staff from two hostels attended a two day training course. Self-perceived
      confidence in supporting residents with deteriorating health, knowledge of
      palliative care, openness to discussing deteriorating health and work related
      stress were assessed at baseline and immediately after training using a novel
      questionnaire. Qualitative data was collected via focus groups immediately after
      and three months post-training. RESULTS: Twenty four participants attended at
      least one day of training, 21 (87%) completed the course. Training was reported
      to be useful and relevant. Modest improvements in self-perceived work related
      stress, knowledge, confidence and openness were observed following training. At
      three months, qualitative data indicated the beginnings of a shift in how
      palliative care was conceptualised and an increase in knowledge and confidence
      around supporting residents. Anxiety regarding the role of the hostel in
      palliative care, the recovery focused ethos of homelessness services and
      fragmented systems and services presented challenges to establishing changes.
      CONCLUSIONS: Training can be useful for improving knowledge, confidence, openness
      and work related stress. Recommendations for implementing changes in how people
      experiencing homelessness are supported include embedding training into routine
      practice, promoting multidisciplinary working, incorporating flexibility within
      the recovery focused approach of services and recognising the need for emotional
      support for staff.

PMID- 30286372
TI  - Staff perception of the sustainability of a mature simulation program in nursing
      and midwifery education: A phenomenological analysis.
AB  - BACKGROUND: As an established pedagogy for teaching clinical nursing skills, the
      use of simulation in nursing and midwifery education continues to increase
      globally. In Australia, government incentives for staff development, capital
      equipment and scenario provided initial impetus for introducing simulation into
      nursing programs. However, a mature simulation program requires ongoing
      investment in staff and resources. Without appropriate commitment from educators
      and organisations, a likely decline in the quality of simulation activities may
      have a direct impact on student learning. PURPOSE: This study sought to explore
      the views and experiences of nursing and midwifery academics involved in
      delivering a simulation-based education program in a maturation phase. METHOD: In
      this qualitative study, interpretative phenomenological analysis was used to
      inform data collection and analysis. Data were collected through semi-structured
      audio-recorded interviews with 10 faculty staff in a tertiary school of nursing
      and midwifery. RESULTS: Four main themes related to simulated learning were
      abstracted from the data: perceptions and reactions, inconsistent customs,
      pedagogy of simulation-based education, and collateral opportunities. The
      findings are located within the context of a maturation, rather than
      introductory, phase of delivering simulation-based education in a tertiary
      education setting. CONCLUSIONS: A mature simulation program may be undermined by
      ageing equipment and scenarios, and facilitators whose skills have not been
      maintained. Existing simulation activities require ongoing organisational support
      and investment. The development and introduction of minimum competency levels for
      facilitators and standardised measures of quality in practice are indicated, to
      improve simulation practice in the education setting.

PMID- 30286373
TI  - Comparing the effects of traditional lecture and flipped classroom on nursing
      students' critical thinking disposition: A quasi-experimental study.
AB  - BACKGROUND: One of the most principal key aims of nursing education is to promote
      nursing students' and nurses' critical thinking. Therefore, nursing education
      needs to develop an appropriate curriculum and use effective instructional
      strategies for critical thinking promotion. Flipped classroom is a teaching
      method which substitutes individual learning for group learning in a dynamic,
      interactive environment where the teacher guides students to understand and use
      concepts. OBJECTIVES: The present study aimed to compare the effects of
      traditional lecture and flipped classroom on Iranian nursing students' critical
      thinking disposition. METHODS: This nonequivalent control group pretest-posttest
      quasi-experimental study was done in 2016 on 85 second-year bachelor's nursing
      students who had signed up for the Musculoskeletal Medical-Surgical Nursing
      theoretical training course. Because of their large number, students had been
      divided at the beginning of the first semester of their four-year program into
      two 42- and 43-student groups and attended separate theoretical training classes.
      These two classes were randomly allocated to either a traditional lecture or a
      flipped classroom group. The instructional strategies in these groups were the
      traditional lecture and the flipped class strategies, respectively. A demographic
      questionnaire and Ricketts' Critical Thinking Disposition Inventory were used for
      data collection. RESULTS: After the intervention, the mean scores of critical
      thinking disposition and its engagement domain in the flipped class group were
      significantly higher than the traditional lecture group (P < 0.0001).
      CONCLUSIONS: This study shows the positive effects of flipped classroom on
      nursing students' critical thinking disposition. It is recommended that future
      studies assess the effects of flipped classroom on other nursing education
      outcomes.

PMID- 30286375
TI  - Engineering hydrogel viscoelasticity.
AB  - The aim of this study was to identify a method for modifying the time-dependent
      viscoelastic properties of gels without altering the elastic component. To this
      end, two hydrogels commonly used in biomedical applications, agarose and
      acrylamide, were prepared in aqueous solutions of dextran with increasing
      concentrations (0%, 2% and 5% w/v) and hence increasing viscosities. Commercial
      polyurethane sponges soaked in the same solutions were used as controls, since,
      unlike in hydrogels, the liquid in these sponge systems is poorly bound to the
      polymer network. Sample viscoelastic properties were characterised using the
      epsilon-dot method, based on compression tests at different constant strain
      rates. Experimental data were fitted to a standard linear solid model. While
      increasing the liquid viscosity in the controls resulted in a significant
      increase of the characteristic relaxation time (tau), both the instantaneous
      (Einst) and the equilibrium (Eeq) elastic moduli remained almost constant.
      However, in the hydrogels a significant reduction of both Einst and tau was
      observed. On the other hand, as expected, Eeq - an indicator of the equilibrium
      elastic behaviour after the occurrence of viscoelastic relaxation dynamics - was
      found to be independent of the liquid phase viscosity. Therefore, although the
      elastic and viscous components of hydrogels cannot be completely decoupled due to
      the interaction of the liquid and solid phases, we show that their viscoelastic
      behaviour can be modulated by varying the viscosity of the aqueous phase. This
      simple-yet-effective strategy could be useful in the field of mechanobiology,
      particularly for studying cell response to substrate viscoelasticity while
      keeping the elastic cue (i.e. equilibrium modulus, or quasi-static stiffness)
      constant.

PMID- 30286374
TI  - Nondestructive characterization of bone tissue scaffolds for clinical scenarios.
AB  - OBJECTIVES: This study aimed to develop a simple and efficient numerical modeling
      approach for characterizing strain and total strain energy in bone scaffolds
      implanted in patient-specific anatomical sites. MATERIALS AND METHODS: A
      simplified homogenization technique was developed to substitute a detailed
      scaffold model with the same size and equivalent orthotropic material properties.
      The effectiveness of the proposed modeling approach was compared with two other
      common homogenization methods based on periodic boundary conditions and the Hills
      energy theorem. Moreover, experimental digital image correlation (DIC)
      measurements of full-field surface strain were conducted to validate the
      numerical results. RESULTS: The newly proposed simplified homogenization approach
      allowed for fairly accurate prediction of strain and total strain energy in
      tissue scaffolds implanted in a large femur mid-shaft bone defect subjected to a
      simulated  in-vivo loading condition. The maximum discrepancy between the total
      strain energy obtained from the simplified homogenization approach and the one
      obtained from detailed porous scaffolds was 8.8%. Moreover, the proposed modeling
      technique could significantly reduce the computational cost (by about 300 times)
      required for simulating an in-vivo bone scaffolding scenario as the required
      degrees of freedom (DoF) was reduced from about 26 million for a detailed porous
      scaffold to only 90,000 for the homogenized solid counterpart in the analysis.
      CONCLUSIONS: The simplified homogenization approach has been validated by
      correlation with the experimental DIC measurements. It is fairly efficient and
      comparable with some other common homogenization techniques in terms of accuracy.
      The proposed method is implicating to different clinical applications, such as
      the optimal selection of patient-specific fixation plates and screw system.

PMID- 30286376
TI  - A material modeling approach for the effective response of planar soft tissues
      for efficient computational simulations.
AB  - One of the most crucial aspects of biomechanical simulations of physiological
      systems that seek to predict the outcomes of disease, injury, and surgical
      interventions is the underlying soft tissue constitutive model. Soft tissue
      constitutive modeling approaches have become increasingly complex, often
      utilizing meso- and multi-scale methods for greater predictive capability and
      linking to the underlying biological mechanisms. However, such modeling
      approaches are associated with substantial computational costs. One solution is
      to use effective constitutive models in place of meso- and multi-scale models in
      numerical simulations but derive their responses by homogenizing the responses of
      the underlying meso- or multi-scale models. A robust effective constitutive model
      can thus drastically increase the speed of simulations for a wide range of meso-
      and multi-scale models. However, there is no consensus on how to develop a single
      effective constitutive model and optimal methods for parameter estimation for a
      wide range of soft tissue responses. In the present study, we developed an
      effective constitutive model which can fully reproduce the response of a wide
      range of planar soft tissues, along with a method for robust and fast-convergent
      parameter estimation. We then evaluated our approach and demonstrated its ability
      to handle materials of widely varying degrees of stiffness and anisotropy.
      Furthermore, we demonstrated the robutst  performance of the meso-structural to
      effective constitutive model framework in finite element simulations of tri
      leaflet heart valves. We conclude that the effective constitutive modeling
      approach has significant potential for improving the computational efficiency and
      numerical robustness of multi-scale and meso-scale models, facilitating efficient
      soft tissue simulations in such demanding applications as inverse modeling and
      growth.

PMID- 30286379
TI  - Experience of perceived barriers and enablers of safe uninterrupted skin-to-skin
      contact during the first hour after birth in Uganda.
AB  - OBJECTIVE: To identify barriers and enablers to conducting safe uninterrupted
      skin-to-skin contact (SSC) in the first hour after birth in a low-resource
      setting and to evaluate how health care professionals coped with the identified
      barriers after completion of an intervention package. DESIGN AND SETTING: A
      qualitative method using focus-group and individual interviews with health
      professionals at a governmental hospital in Uganda. PARTICIPANTS: 81 health
      professionals. INTERVENTIONS: A 6-step intervention package including, amongst
      other things, showing a DVD on safe uninterrupted SSC following birth and
      discussing with the professionals what barriers and possibilities there were to
      changing practice to allow SSC for one hour. MEASUREMENTS AND FINDINGS: The
      thematic analysis of the intervention interviews yielded the following themes:
      Perceived barriers including medical events, psychosocial issues and standard
      midwifery practice; Pragmatic barriers including economic constraints in the
      hospital and community; Anticipated barriers by staff and families; Enabling
      events including staff involvement. Most of the barriers involving expenses were
      not solved. When the mother and infant had to move to the postnatal ward within
      one hour after birth, there were difficulties in keeping SSC during the
      transportation, but this obstacle was partly solved. A few mothers (i.e.
      depressed and/or adolescent) were considered to be unwilling to keep the infant
      skin-to-skin; this difficulty was not solved. Practising SSC led the participants
      to find advantages such as reduced work load and positive effects on pain during
      suturing. CONCLUSIONS: SSC following birth was shown to be applicable and
      accepted by the health professionals. The involvement of professionals had
      clinical implications, such as initiatives to broadcast the message of SSC by
      radio to the community and introduce SSC to women having a Caesarean section.

PMID- 30286377
TI  - Calorie restriction attenuates hypertrophy-induced redox imbalance and
      mitochondrial ATP-sensitive K+ channel repression.
AB  - Oxidative stress has been implicated in the pathogenesis of cardiac hypertrophy
      and associated heart failure. Cardiac tissue grows in response to pressure or
      volume overload, leading to wall thickening or chamber enlargement. If sustained,
      this condition will lead to a dysfunctional cardiac tissue and oxidative stress.
      Calorie restriction (CR) is a powerful intervention to improve health and delay
      aging. Here, we investigated whether calorie restriction in mice prevented
      isoproterenol-induced cardiac hypertrophy in vivo by avoiding reactive oxygen
      species (ROS) production and maintaining antioxidant enzymatic activity.
      Additionally, we investigated the involvement of mitochondrial ATP-sensitive K+
      channels (mitoKATP) in cardiac hypertrophy. CR was induced by 40% reduction in
      daily calorie ingestion. After 3 weeks on CR or ad libitum (Control) feeding,
      Swiss mice were treated intraperitoneally with isoproterenol (30 mg/kg per day)
      for 8 days to induce hypertrophy. Isoproterenol-treated mice had elevated heart
      weight/tibia length ratios and cardiac protein levels. These gross hypertrophic
      markers were significantly reduced in CR mice. Cardiac tissue from isoproterenol
      treated CR mice also produced less H2O2 and had lower protein sulfydryl
      oxidation. Additionally, calorie restriction blocked hypertrophic-induced
      antioxidant enzyme (catalase, superoxide dismutase and glutathione peroxidase)
      activity repression during cardiac hypertrophy. MitoKATP opening was repressed in
      isolated mitochondria from hypertrophic hearts, in a manner sensitive to calorie
      restriction. Finally, mitoKATP inhibition significantly blocked the protective
      effects of calorie restriction. Altogether, our results suggest that CR improves
      intracellular redox balance during cardiac hypertrophy and prevents this process
      in a mechanism involving mitoKATP activation.

PMID- 30286380
TI  - Efficacy of a multidisciplinary approach on postoperative morbidity and mortality
      of elderly patients with hip fracture.
AB  - STUDY OBJECTIVE: We evaluated the efficacy of a multidisciplinary approach to
      reduce postoperative complications and 1-year mortality in patients, undergoing
      hip fracture surgery and the impact of surgical delay on mortality. DESIGN: A non
      randomized intervention study with a historical control group (CG). SETTING:
      During the hospital stay of patients undergoing hip fracture surgery and
      subsequent follow-up during 12 months post-discharge. PATIENTS: 240 patients
      undergoing hip fracture surgery were included in the CG. 272 patients were
      included in the intervention group (IG). INTERVENTIONS: CG patients received the
      standard care given at our hospital. Patients in the IG received a new model of
      multidisciplinary approach to care. MEASUREMENTS: The following variables were
      collected: study group, age, gender, ASA physical status, comorbidity, type of
      fracture, type of anaesthesia, surgical delay, postoperative complications,
      hospital stay, destination after discharge and postoperative mortality. MAIN
      RESULTS: 512 patients (CG = 240; IG = 272). Mean age was 83.8 years in CG and
      84.9 years in IG. Patients in the IG had a worse health status according to ASA
      (III-IV: 68.8% vs 51.7%; p < 0.001) and took more drugs (p < 0.001). Surgery was
      performed within 48 h of admission in 55.1% of patients of the IG (38.3% CG; p <
      0.001). Incidence of postoperative complications (67.3% IG vs 76.2% CG p = 0.025)
      and hospital stay was shorter in the IG (p < 0.001). A surgical delay of >48 h
      (HR = 0.61; CI95%: 0.42-0.88) and allocation to the IG (HR = 0.64; CI95%: 0.44
      0.93) were the protective factors for mortality. CONCLUSIONS: The
      multidisciplinary approach could be associated with a decrease in postoperative
      complications, hospital stay and mortality. Surgical delay may not increase the
      risk of mortality. The main objective in the management of these patients should
      be the optimization of their general health status before surgery rather than
      surgical delay.

PMID- 30286381
TI  - Intraindividual sleep variability and its association with insomnia identity and
      poor sleep.
AB  - OBJECTIVE: Insomnia identity refers to the conviction that one has insomnia,
      which can occur independently of poor sleep. Night-to-night variability in sleep
      (termed intraindividual variability [IIV]) may contribute to insomnia identity
      yet remain undetected via conventional mean analyses. This study compared sleep
      IIV across four subgroups: noncomplaining good sleepers (NG), complaining poor
      sleepers (CP), complaining good sleepers (CG), and noncomplaining poor sleepers
      (NP). METHODS: This study analyzed 14 days of sleep diary data from 723 adults.
      Participants were classified according to presence/absence of a sleep complaint
      and presence/absence of poor sleep. A 2 * 2 multivariate analysis of covariance
      (MANCOVA) was performed to explore differences on five measures of sleep IIV:
      intraindividual standard deviation in total sleep time (iSD TST), sleep onset
      latency (iSD SOL), wake after sleep onset (iSD WASO), number of nightly
      awakenings (iSD NWAK), and sleep efficiency (iSD SE). RESULTS: MANCOVA revealed
      significant main effects of poor sleep, sleep complaint, and their interaction on
      sleep IIV. Poor sleepers exhibited greater IIV across all sleep parameters
      compared to good sleepers. Similarly, individuals with a sleep complaint
      exhibited greater IIV compared to individuals with no complaint. The interaction
      revealed that iSD SOL was significantly greater among CP than NP, and iSD NWAK
      was significantly greater among CG than NG. CONCLUSIONS: Greater night-to-night
      variability in specific sleep parameters was present among complaining versus
      noncomplaining sleepers in good and poor sleep subgroups. These findings suggest
      certain aspects of sleep consistency may be salient for treatment-seeking
      individuals based on their quantitative sleep status.

PMID- 30286378
TI  - Common gut microbial metabolites of dietary flavonoids exert potent protective
      activities in beta-cells and skeletal muscle cells.
AB  - Flavonoids are dietary compounds with potential anti-diabetes activities. Many
      flavonoids have poor bioavailability and thus low circulating concentrations.
      Unabsorbed flavonoids are metabolized by the gut microbiota to smaller
      metabolites, which are more bioavailable than their precursors. The activities of
      these metabolites may be partly responsible for associations between flavonoids
      and health. However, these activities remain poorly understood. We investigated
      bioactivities of flavonoid microbial metabolites [hippuric acid (HA),
      homovanillic acid (HVA), and 5-phenylvaleric acid (5PVA)] in primary skeletal
      muscle and beta-cells compared to a native flavonoid [(-)-epicatechin, EC]. In
      muscle, EC was the most potent stimulator of glucose oxidation, while 5PVA and HA
      simulated glucose metabolism at 25 MUM, and all compounds preserved mitochondrial
      function after insult. However, EC and the metabolites did not uncouple
      mitochonndrial respiration, with the exception of 5PVA at10 MUM. In beta-cells,
      all metabolites more potently enhanced glucose-stimulated insulin secretion
      (GSIS) compared to EC. Unlike EC, the metabolites appear to enhance GSIS without
      enhancing beta-cell mitochondrial respiration or increasing expression of
      mitochondrial electron transport chain components, and with varying effects on
      beta-cell insulin content. The present results demonstrate the activities of
      flavonoid microbial metabolites for preservation of beta-cell function and
      glucose utilization. Additionally, our data suggest that metabolites and native
      compounds may act by distinct mechanisms, suggesting complementary and
      synergistic activities in vivo which warrant further investigation. This raises
      the intriguing prospect that bioavailability of native dietary flavonoids may not
      be as critical of a limiting factor to bioactivity as previously thought.

PMID- 30286382
TI  - Association between sleep duration during pregnancy and gestational diabetes
      mellitus: a meta-analysis.
AB  - OBJECTIVE: Sleep is critical for glucose metabolism. Pregnant women often have
      sleep disturbances and extreme sleep duration. Investigations of the relationship
      between sleep duration during pregnancy and gestational diabetes mellitus (GDM)
      have reported inconsistent results. The present study aimed to meta-analyze the
      relationship between sleep duration during pregnancy and GDM risk. METHODS: We
      performed a systematic search of the PubMed, ISI Web of Science, and PsycINFO
      databases for studies that were published up to October 2017, that reported
      associations between sleep duration during pregnancy and GDM risk. Odds ratios
      (ORs) and 95% confidence intervals (CIs) were calculated as the effect sizes for
      all studies. Heterogeneity and potential publication biases were assessed.
      RESULTS: A total of 4366 papers were retrieved, among which seven studies
      assessed the relationship between sleep duration during pregnancy and GDM
      development. The seven articles included 18,203 subjects at baseline and 1294 GDM
      cases during follow-up. Compared to normal sleep duration, extreme sleep duration
      during early and middle pregnant stages had a close relationship with GDM based
      upon pooled data from prospective and cross-sectional studies. Prospective
      results showed that long sleep duration during pregnancy was a risk factor for
      GDM, but not short sleep duration. Publication biases were found when analyzing
      the relationship between extreme sleep duration and GDM. CONCLUSIONS: Extreme
      sleep duration during pregnancy is closely associated with GDM. Moreover, long
      but not short sleep duration can predict the risk of developing GDM. These
      findings remind us of the importance of sleep duration control during pregnancy
      and help optimize early strategies for the prevention of GDM.

PMID- 30286383
TI  - Last night's sleep in relation to academic achievement and neurocognitive testing
      performance in adolescents with and without ADHD.
AB  - OBJECTIVES/BACKGROUND: Objectives were to (1) examine previous night's sleep in
      relation to next day performance on standardized academic achievement and
      neurocognitive assessments in adolescents, and (2) explore whether previous
      night's sleep is differentially associated with testing performance for
      adolescents with and without attention-deficit/hyperactivity disorder (ADHD).
      PARTICIPANTS/METHODS: Participants were 300 adolescents (ages 12-14 years; 55%
      male). Approximately half (53.6%) were diagnosed with ADHD. Adolescents provided
      ratings of their previous night's sleep quality, sleep duration, and number of
      night wakings and were administered standardized tests of processing speed and
      working memory, as well as word reading, numerical operations, and math fluency
      academic achievement. RESULTS: In analyses controlling for sex, race, medication
      use, time of testing, and ADHD group status, more night wakings the previous
      night were associated with significantly lower numerical operations and math
      fluency achievement scores and marginally lower working memory scores. Previous
      night's sleep was not associated with processing speed or reading achievement.
      ADHD status did not moderate sleep in relation to academic/neurocognitive
      performance. Participants reporting >=2 night wakings the previous night had
      slightly over half a standard deviation lower scores on average compared to
      participants reporting 0 night wakings. CONCLUSIONS: This preliminary study
      suggests that previous night's wakings are associated with poorer mathematics
      performance the next day, regardless of ADHD status. This may be due to the
      detrimental effect of interrupted and fragmented sleep on attention and executive
      control. These findings have implications for clinicians and educators when
      considering contextual factors that may impact academic and neurocognitive
      testing performance.

PMID- 30286384
TI  - Assessment of change in restless legs syndrome symptoms during the acute drug
      withdrawal period.

PMID- 30286385
TI  - Using actigraphy to assess sleep and wake rhythms of narcolepsy type 1 patients:
      a comparison with primary insomniacs and healthy controls.
AB  - OBJECTIVE/BACKGROUND: It has been shown that actigraphy may have a discriminant
      function (DS) for the diagnosis of narcolepsy type 1 patients (NT1), based on a
      combination of nighttime and daytime parameters. Here, we aimed to test those
      findings using another actigraph model with a different clinical sample as
      control (ie, primary insomniacs, PI), carrying out a secondary analysis of
      previously collected data. PATIENTS/METHODS: The study sample consisted of 13 NT1
      (nine females; mean age 39.38 +/- 11.48), 13 PI (nine females; mean age 38.69 +/-
      10.72) and 13 Healthy Controls (HC) (nine females; mean age 38 +/- 10.77).
      Participants wore the Actiwatch AW64 (Cambridge Neurotechnology Ltd, Cambridge,
      UK) around the non-dominant wrist for seven consecutive days. RESULTS:
      Significant differences between groups were observed with a higher number of
      episodes of wakefulness (wake bouts, WB) in PI than HC, a higher fragmentation
      index (FI) in NT1 than HC and PI, a higher duration of the longest nap (LNAP) in
      NT1 than HC and PI and higher DS in PI and NT1 than HC. A new DS (NDS), with LNAP
      and FI as independent variables, was proposed; which was higher in NT1 than HC
      and PI. CONCLUSIONS: The present study confirms that actigraphy discriminates NT1
      from HC. However, considering PI, a new discriminant function NDS which takes
      into account LNAP and FI is better for this actigraph model.

PMID- 30286387
TI  - The genetic makings of South Asia.
AB  - South Asia is home for more than a billion people culturally structured into
      innumerable groups practicing different levels of endogamy. Linguistically South
      Asia is broadly characterized by four major language families which has served as
      access way for disentangling the genetic makings of South Asia. In this review we
      shall give brief account on the recent developments in the field. Advances are
      made in two fronts simultaneously. Whole genome characterisation of many extant
      South Asians paint the picture of the genetic diversity and its implications to
      health-care. On the other hand ancient DNA studies, which are finally reaching
      South Asia, provide new incites to the demographic history of the subcontinent.
      Before the spread of agriculture, South Asia was likely inhabited by hunter
      gatherer groups deriving much of their ancestry from a population that split from
      the rest of humanity soon after expanding from Africa. Early Iranian
      agriculturalists mixing with these local hunter-gatherers probably formed the
      population that flourished during the blossoming of the Indus Valley
      Civilisation. Further admixture with the still persisting HG groups and
      population(s) from the Eurasian Steppe, formed the two ancestral populations (ANI
      and ASI), the north-south mixing pattern of whom is known today as the 'Indian
      Cline'. Studies on natural selection in South Asia have so far revealed strong
      signals of sweeps that are shared with West Eurasians. Future studies will have
      to fully unlock the aDNA promise for South Asia.

PMID- 30286386
TI  - Disruption of superficial white matter in the emotion regulation network in
      bipolar disorder.
AB  - Bipolar disorder (BD) is characterized by emotion dysregulation and involves
      changes in the gray matter (GM) and white matter (WM). Although previous
      diffusion tensor imaging (DTI) studies reported changes in the diffusion
      properties of the deep WM (DWM) in BD patients, the diffusion properties of the
      superficial WM (SWM) are rarely investigated. In this study, we tried to
      determine whether the diffusion parameters of the SWM were altered in BD patients
      compared to controls and whether the changes were associated with the disrupted
      emotion regulation of the BD patients. We collected DTI data from 37 BD patients
      and 42 gender- and age-matched healthy controls (HC). Using probabilistic
      tractography, we defined a population-based SWM mask based on all the subjects.
      After performing the tract-based spatial statistical (TBSS) analyses, we
      identified the SWM areas in which the BD patients differed from the controls.
      This study showed significantly reduced fractional anisotropy in the SWM (FASWM)
      in the BD patients compared to the HC in the bilateral dorsolateral prefrontal
      cortex (dlPFC), ventrolateral prefrontal cortex (vlPFC), medial prefrontal cortex
      (mPFC), and the left parietal cortex. Moreover, compared to the controls, the BD
      patients showed significantly increased mean diffusivity (MDSWM) and radial
      diffusivity (RDSWM) in the SWM in the right frontal cortex. This study presents
      altered cortico-cortical connections proximal to the regions related to the
      emotion dysregulation of BD patients, which indicated that the SWM may serve as
      the brain's structural basis underlying the disrupted emotion regulation of BD
      patients. The disrupted FASWM in the parietal cortex may indicate that the
      emotion dysregulation in BD patients is related to the cognitive control network.

PMID- 30286388
TI  - Rare atlas fracture detected using postmortem computed tomography: A case report.
AB  - We report the autopsy of a traffic accident victim with a rare atlas fracture.
      The deceased was 52-year-old man found dead on the road because of a traffic
      accident. We performed a postmortem computed tomography and an autopsy on the
      body. The sagittal reformation image of postmortem computed tomography showed a
      vertically separated anterior arch of atlas, suggesting a "horizontal fracture."
      Therefore, we assumed that cervical hyperextension may have been one of the
      forces that affected him during the accident. Minor spinal cord injury was also
      noted. In this case, postmortem computed tomography played an important role in
      detecting the spinal cord injury, considering the mechanism of the traffic
      accident, and supported the autopsy.

PMID- 30286389
TI  - Developmental evidence for a link between the inherence bias in explanation and
      psychological essentialism.
AB  - The assumption that natural and social categories have deeper "essences" is a
      fundamental feature of the conceptual system, with wide-ranging consequences for
      behavior. What are the developmental origins of this assumption? We propose that
      essentialism emerges in part from a bias in the process of generating
      explanations that leads reasoners to overuse inherent or intrinsic features.
      Consistent with this proposal, the inherence bias in 4-year-olds' explanations
      predicted the strength of their essentialist beliefs (Study 1; N = 64), and
      manipulations of the inherence bias in 4- to 7-year-olds (Studies 2 and 3; N =
      112 each) led to subsequent changes in the essentialist beliefs of children who
      attended to the manipulation. These findings contribute to our understanding of
      the origins of essentialism.

PMID- 30286390
TI  - Convulsive seizures and EEG spikes after lateral fluid-percussion injury in the
      rat.
AB  - The rat lateral fluid-percussion injury (FPI) model has been used extensively to
      study post-traumatic epilepsy (PTE). Epidemiological studies have reported that
      the risk of PTE is higher after more severe injury. Adult, male Wistar rats
      subjected to different atmospheric pressures of injury during FPI showed great
      variability in injury severity when functional behavior was determined based on
      the Neurological Severity Score (NSS) assessment. When NSS was used to select
      rats with the most severe FPI-induced brain injury, 63% of rats experienced at
      least one convulsive seizure 2-5 weeks after FPI. This same cohort of rats (i.e.,
      selected for severe TBI based on NSS) were significantly more susceptible to PTZ
      induced seizures compared to sham controls. Video/EEG recordings from a second
      cohort of rats with severe FPI-induced injury (based on NSS) showed a similar
      incidence and frequency of spike wave discharges between rats with severe TBI and
      sham controls. However, the rate of isolated EEG spikes was greater in rats with
      severe FPI-induced injury compared to sham controls. These data suggest that
      convulsive seizures can be obtained in FPI-treated rats when NSS is used as an
      inclusion criterion to select rats with severe injury. Furthermore, although
      spike-wave discharges were equally prevalent in rats with severe FPI and sham
      controls, spontaneous spikes were more prevalent in the rats with severe FPI.

PMID- 30286391
TI  - Diagnosis switching and outcomes in a cohort of patients with potential epilepsy
      with myoclonic-atonic seizures.
AB  - INTRODUCTION: There is overlap in the electroclinical features of many childhood
      epilepsy syndromes, especially those presenting with multiple seizure types, such
      as epilepsy with myoclonic-atonic seizures (EMAS) and Lennox-Gastaut syndrome
      (LGS). This study aimed to determine the frequency of diagnosis switching and the
      factors influencing epilepsy syndrome diagnosis in a cohort of children with
      possible EMAS, as well as to explore the relationship between epilepsy syndrome
      diagnoses, key electroclinical features, and clinically relevant outcomes.
      METHODS: This is a cross-sectional retrospective chart review of children treated
      at the Children's Hospital of Colorado with a potential diagnosis of EMAS.
      RESULTS: There were 77 patients that met eligibility criteria, including 39% (n =
      30) with an initial diagnosis of EMAS and 74% (n = 57) with a final diagnosis of
      EMAS. On average, for the 65% of patients who received more than one epilepsy
      diagnosis, the first, second, and third diagnoses were received within one year,
      three years, and ten years after epilepsy onset, respectively. Final diagnosis
      was significantly related to obtaining at least a six-month period of seizure
      freedom, p = 0.03. Classic LGS traits, including paroxysmal fast activity, slow
      spike-and-wave, and tonic seizures were present in 50% of the overall cohort,
      although a minority of these patients had a final diagnosis of LGS. However, the
      presence of more LGS traits was associated with a higher likelihood of ongoing
      seizures. Adjusted for age of epilepsy onset, seizure freedom was half as likely
      for every additional LGS trait observed (0.49[0.31, 0.77], p = 0.002).
      CONCLUSION: Current epilepsy syndrome classification has reduced applicability
      due to overlapping features. This results in diagnosis switching and limited
      prognostic value for patients with an overlapping clinical phenotype. Future
      studies should attempt to stratify patients based not only on epilepsy syndrome
      diagnosis, but also on the presence of various electroclinical traits to more
      accurately predict outcome.

PMID- 30286392
TI  - Theoretical study for anisotropic responses of the condensed-phase RDX under
      shock loadings.
AB  - We have performed quantum-based molecular dynamics (MD) simulations in
      conjunction with multiscale shock technique (MSST) to investigate the initial
      chemical processes and the anisotropy of shock sensitivity of the RDX under shock
      loading applied along the different directions. The results show that there is a
      difference between x (or y)-direction and z-direction in the response to a shock
      wave velocity of 12 km/s. It was shown that detonation temperature and pressure
      in the z-direction lags behind that of x-direction (or y-direction). Moreover,
      from the time evolution of the population of various key fragments, we also
      observe that along with z-direction significantly later than that of x (or y)
      direction, which the reaction rate is also slower. Thus, we draw a conclusion
      that sensitive for shock propagation along x or y-direction, but less sensitive
      for shock propagation along z-direction.

PMID- 30286393
TI  - A comparative DFT study on single-atom catalysis of CO oxidation over Al- and P
      embedded hexagonal boron-nitride nanosheets.
AB  - Density functional theory calculations are performed to compare catalytic
      oxidation of CO molecule over Al- and P-embedded hexagonal boron nitride
      nanosheet (h-BN). It is found that the Al and P adatom can be stably anchored on
      the boron-vacancy site of h-BN, as evidenced by a relatively large adsorption
      energy and charge-transfer value. According to our findings, the oxidation of CO
      over these surfaces proceeds via the Langmuir-Hinshelwood mechanism, followed by
      the elimination of the remaining atomic O by another CO molecule. Meanwhile, the
      stronger adsorption of O2 than CO avoids poisoning of the active site of both
      surfaces. The results of the present study indicate that Al-doped h-BN exhibits
      higher catalytic activity for CO oxidation than P-doped one, which may provide a
      valuable guidance on design metal-free catalysts to remove toxic CO molecules.

PMID- 30286394
TI  - Combined dilute hydrochloric acid and alkaline wet oxidation pretreatment to
      improve sugar recovery of corn stover.
AB  - Two-stage dilute hydrochloric acid (DA)/aqueous ammonia wet oxidation (AWO)
      pretreatment was used to recover the sugars of corn stover. The morphology
      characterizations of samples were detected by SEM, BET and SXT. The results
      showed that DA-AWO process demonstrated a positive effect on sugar recovery
      compared to AWO-DA. 82.8% of xylan was recovered in the first stage of DA-AWO
      process at 120  degrees C for 40 min with 1 wt% HCl. The second stage was
      performed under relative mild reaction conditions (130  degrees C, 12.6 wt%
      ammonium hydroxide, 3.0 MPa O2, 40 min), and 86.1% lignin could be removed. 71.5%
      of glucan was achieved with a low enzyme dosage (3 FPU.g-1) in the following
      enzymatic hydrolysis. DA-AWO pretreatment was effective due to its sufficient
      hydrolysis of hemicellulose in the first stage and remarkably removal of the
      lignin in the second stage, resulting in high sugar recovery with a low enzyme
      dosage.

PMID- 30286396
TI  - Emotion regulation difficulties and social control correlates of smoking among
      pregnant women trying to quit.
AB  - Approximately 15% of US women currently smoke during pregnancy. An important step
      toward providing effective smoking cessation interventions during pregnancy is to
      identify individuals who are more likely to encounter difficulty quitting.
      Pregnant smokers frequently report smoking in response to intrapersonal factors
      (e.g., negative emotions), but successful cessation attempts can also be
      influenced by interpersonal factors (i.e., influence from close others). This
      study examined the association between emotion regulation difficulties, positive
      and negative social control (e.g., encouragement, criticism), and smoking
      cessation-related variables (i.e., smoking quantity, withdrawal symptoms) among
      pregnant smokers. Data were drawn from the pretreatment wave of a smoking
      cessation trial enrolling low-income pregnant women who self-reported smoking in
      response to negative affect (N = 73). Greater emotion regulation difficulties
      were related to greater smoking urges (b = 0.295, p = .042) and withdrawal
      symptoms (b = 0.085, p = .003). Additionally, more negative social control from
      close others was related to fewer smoking days (b = -0.614, p = .042) and higher
      smoking abstinence self-efficacy (b = 0.017, p = .002). More positive social
      control from close others interacted with negative affect smoking (b = -0.052, p
      = .043); the association between negative affect smoking and nicotine dependence
      (b = 0.812, p < .001) only occurred at low levels of positive social control.
      Findings suggest that emotion regulation difficulties may contribute to smoking
      during pregnancy by exacerbating women's negative experiences related to smoking
      cessation attempts. Negative social control was related to lower smoking
      frequency and greater confidence in quitting smoking, suggesting that it may
      assist pregnant smokers' cessation efforts. Positive social control buffered
      women from the effects of negative affect smoking on nicotine dependence. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT01163864.

PMID- 30286395
TI  - Pd-CuFe Catalyst for Transfer Hydrogenation of Nitriles: Controllable Selectivity
      to Primary Amines and Secondary Amines.
AB  - A multicomponent nanocatalyst system was fabricated for the transfer
      hydrogenation of nitrile compounds. This catalyst system contains palladium,
      copper, and iron, which are supported on the magnetite nanospheres, and the
      loading of palladium could be at the parts per million level. Palladium and
      copper contribute to the transformation of nitrile, and the product distribution
      highly depends on the alloying of Fe to Cu. The nitriles could be converted to
      primary amine by the Pd-Cu catalyst in the absence of Fe, whereas in the presence
      of Fe the products are secondary amines with high selectivity. This could be
      attributed to the electronic modulation of iron to copper. A variety of nitriles
      have been transformed to the corresponding primary or secondary amines with high
      selectivity, and the TOF reaches 2,929 hr-1 for Pd. Furthermore, the catalyst
      could be recycled by an external magnetic field and reused five times without
      severe activity loss.

PMID- 30286397
TI  - Phenotypic and genetic relationship between BMI and cigarette smoking in a sample
      of UK adults.
AB  - In addition to the health hazards posed individually by cigarette smoking and
      obesity, the combination of these conditions poses a particular impairment to
      health. Genetic factors have been shown to influence both traits and, to
      understand the connection between these conditions, we examined both the observed
      and genetic relationship between adiposity (an electrical impedance measure of
      body mass index (BMI)) and cigarettes smoked per day (CPD) in a large sample of
      current, former, and never smokers in the United Kingdom. In former smokers, BMI
      was positively associated with cigarettes formerly smoked; further, the genetic
      factors related to a greater number of cigarettes smoked were also responsible
      for a higher BMI. In current smokers, there was a positive association between
      BMI and number of cigarettes smoked, though this relationship did not appear to
      be influenced by similar genetic factors. We found a positive genetic
      relationship between smoking in current/former smokers and BMI in never smokers
      (who would be unmarred by the effects of nicotine). In addition to CPD, in
      current smokers, we looked at two variables, time from waking to first cigarette
      and difficulty not smoking for a day, that may align better with cigarette and
      food 'craving.' However, these smoking measures provided mixed findings with
      respect to their relationship with BMI. Overall, the positive relationships
      between the genetic factors that influence CPD in smokers and the genetic factors
      that influence BMI in former and never smokers point to common biological
      influences behind smoking and obesity.

PMID- 30286398
TI  - Effect of coexisting ions on Cr(VI) adsorption onto surfactant modified
      Auricularia auricula spent substrate in aqueous solution.
AB  - In this paper, the effect of coexisting cations and anions on Cr(VI)(in the form
      of Cr2O72-) adsorption onto Auricularia auricula spent substrate (AASS) modified
      by cetyl trimethyl ammonium bromide (CTAB) was investigated in batch adsorption
      experiment. The Cr(VI) adsorption capacity of 9.327 mg/g, obtained at pH 3.0, 303
      K, adsorbent dosage of 2 g/L, initial Cr(VI) concentration of 20 mg/L, rotational
      speed of 150 r/min for 120 min, was decreased in the presence of coexisting
      cations and anions, among which Pb2+ and PO43- affected most by 21.79% and
      12.43%, respectively. XRD, XPS and FTIR detection found that coexisting Pb2+ and
      PO43- would not only interfere Cr(VI) to form crystals and reduce to Cr(III), but
      also compete with Cr(VI) for oxygen-containing and amino groups to form Pb-O and
      P-NH2, respectively. In addition, the single Cr(VI) adsorption fitted with
      Langmuir isotherm model, while the competitive adsorption was well described by
      Freundlich isotherm model. Both single adsorption and competitive adsorption were
      in line with the pseudo-second-order kinetic model.

PMID- 30286399
TI  - LAP it up, fuzz ball: a short history of LC3-associated phagocytosis.
AB  - LC3-associated phagocytosis (LAP) exists at the crossroads of the two
      evolutionary pathways of phagocytosis and autophagy. When a phagocyte engulfs an
      extracellular particle that engages receptor signaling, components of the
      autophagy machinery and Rubicon are recruited to the cargo-containing phagosome
      or LAPosome. Formation of the LAPosome is critical for both cargo clearance as
      well as mediating the proper signaling cascade. Globally, LAP functions as an
      immunosuppressive mechanism, as LAP deficiency often results in
      hyperinflammation. As defects in the autophagy machinery have been long
      associated with aberrant immune responses and autoimmune disorders, it is vital
      that we now revisit these associations with forms of non-canonical autophagy,
      like LAP, in mind.

PMID- 30286400
TI  - Open path incoherent broadband cavity-enhanced measurements of NO3 radical and
      aerosol extinction in the North China Plain.
AB  - We describe the observation of the NO3 radical using an incoherent broadband
      cavity-enhanced absorption spectrometer in an open-path configuration (OP
      IBBCEAS) in a polluted summer environment in continental China. The instrument
      was installed 17 m above the ground at the top of a residential complex near the
      CAREBeijing-NCP 2014 site in Wangdu, Hebei province, about 200 km southwest of
      Beijing over the period 28 to 30 June 2014. The separation between the
      transmitter and receiver components of the instrument was 335 cm and the
      effective pathlength in clean reference air was ~3.4 km. NO3 was detected above
      the detection limit on all three nights when the instrument was operational. The
      maximum mixing ratio measured was ~175 pptv with a detection sensitivity of ~36
      pptv for measurements with an average acquisition time of 10 min. While most
      extractive instruments try to avoid interferences arising from aerosol
      extinction, the open path configuration has advantages owing to its ability to
      detect trace gases even in the presence of aerosol loading. Moreover, concurrent
      retrieval of aerosol optical extinction is possible from analysis of the
      absorption magnitude of the oxygen B-band at 687 nm. The experimental setup, its
      calibration, data acquisition, and analysis procedure are discussed, and the
      results presented here demonstrate the sensitivity and specificity that can be
      achieved at high spatial and temporal resolution using the novel configuration of
      IBBCEAS in the open path.

PMID- 30286401
TI  - Patient views regarding the impact of hydrotherapy on critically ill ventilated
      patients: A qualitative exploration study.
AB  - BACKGROUND: Intensive Care Unit Acquired Weakness can be mitigated by early
      activity and progressive mobilization. Hydrotherapy enables patients to work on
      their recovery in a very early stage. This may lead to higher levels of self
      efficacy, subsequently higher activity-rates and faster functional recovery.
      Hydrotherapy might positively affect the regaining of control, hope and trust.
      Our aim is to explore patient perspective regarding the impact of hydrotherapy on
      critically ill ventilated patients. METHODS: This qualitative exploration study
      adopted an interpretative phenomenological approach using in-depth, face to face,
      semi-structured interviews. Questions covered: pre-admission physical activity,
      perception of hydrotherapy, affection to water, positive and negative experiences
      and feelings towards the recovery process. Interviews were analyzed using
      thematic analysis. RESULTS: Twelve patients were enrolled, of which eight could
      be interviewed. After analyzing, five main themes were found: experiencing
      consequences of critical illness, feeling safe in the water, being able to move,
      positive experiences relating to hydrotherapy and experiencing a turning point.
      CONCLUSIONS: Hydrotherapy seemed to help patients regain control and belief in
      their recovery. Patients experienced exercising in water as a turning point in
      their recovery process. This study encourages to continue providing hydrotherapy
      to critically ill ventilated patients and may stimulate future research.

PMID- 30286402
TI  - Lower serum kallistatin level is associated with 28-day mortality in patients
      with septic shock.
AB  - PURPOSE: Investigation for whether serum levels of kallistatin, vascular cell
      adhesion molecule-1 (VCAM-1), and E-selectin are associated with outcomes in
      patients with septic shock MATERIAL AND METHODS: Biomarker levels were measured
      using blood samples from patients with septic shock at admission, 24 h, and 72 h
      and from healthy volunteers. The primary outcome was 28-day mortality. RESULTS:
      Fifty-eight survivors, fourteen non-survivors, and six healthy volunteers were
      enrolled. Serum kallistatin level was lower and serum VCAM-1 and E-selectin
      levels were higher in patients at admission compared with healthy volunteers.
      Serum kallistatin levels were higher in survivors compared with non-survivors at
      all time points (4.4 MUg/mL [2.9-6.1] vs. 2.5 MUg/mL [2.1-5.0], P = 0.019 at
      admission; 4.3 MUg/mL [3.3-5.2] vs. 3.2 MUg/mL [2.2-3.8], P = 0.004 at 24 h; 3.1
      MUg/mL [2.5-4.2] vs. 2.3 MUg/mL [1.7-3.1], P = 0.012 at 72 h), while VCAM-1 and E
      selectin levels showed no difference. In the multivariable analysis, serum
      kallistatin level at 24 h was independently associated with 28-day mortality (OR,
      0.29; 95% CI, 0.08-0.69, P = 0.024). CONCLUSIONS: Lower serum kallistatin level
      at 24 h was independently associated with 28-day mortality in patients with
      septic shock.

PMID- 30286403
TI  - Validation of The Critical-care Pain Observation Tool (CPOT) for the detection of
      oral-pharyngeal pain in critically ill adults.
AB  - OBJECTIVE: Mechanically ventilated patients experience pain at rest and during
      daily care procedures. Our objective was to test the reliability and validity of
      the Critical-Care Pain Observation Tool (CPOT) to detect oral-pharyngeal pain in
      intubated and tracheostomised adults during routine oral care procedures.
      MATERIALS AND METHODS: Two trained research team members independently observed
      patients during two non-painful (rest and gentle touch) and three potentially
      painful (oral suctioning, tooth brushing, and swabbing with a sponge toothette)
      procedures. Conscious patients were asked if they experienced pain during each
      procedure (yes/no) and to rate their pain intensity on a 0 to 10 numeric rating
      scale. RESULTS: A total of 98 patients, primarily intubated (92.9%) and male
      (63.3%) participated. Criterion validation was supported by patient self-report
      of pain during tooth brushing (AUC=.80; P<0.5) and oral suction (AUC=.72; P<0.3)
      but not for oral swabbing (AUC=.68; P=0.16). Discriminative validation was
      demonstrated for all oral care procedures compared to rest (P<.001). Intra-class
      correlation coefficients between raters ranged from .78 to .91 (P<.001) for total
      CPOT scores, indicating excellent inter-rater reliability. CONCLUSIONS: The CPOT
      is reliable and valid for the detection of oral-pharyngeal pain during oral care
      procedures indicated as painful by critically ill adults.

PMID- 30286404
TI  - Effect of drought stress on metabolite adjustments in drought tolerant and
      sensitive thyme.
AB  - Drought is one of the most important threats to plants and agriculture;
      therefore, understanding of the mechanism of drought tolerance is crucial for
      breeding of drought tolerant plants. Here, we assessed effects of four levels of
      drought (90%, 55%, 40% and 25% FC) on some physiological criteria and metabolite
      adjustment of two different drought-responsive thyme plants (Thymus vulgaris as
      drought sensitive and T. Kotschyanus as drought tolerant species), using 1H-NMR.
      Among three physiological parameters and 18 identified metabolites, species *
      treatment effects were significant (P <= 0.01) for leaf temperature, acetic acid,
      citric acid, fumaric acid, malic acid, succinic acid, fructose, sucrose and
      serine. RWC, chlorophyll and carotenoids content, glucose, alanine and choline
      were affected by simple effects of species and treatment. Correlation analysis
      revealed that there is a different correlation between physiological parameters
      and metabolites in both species. This analysis also revealed that, by ignoring
      the correlation between malic acid and succinic acid in T. vulgaris, there was no
      significant correlation between TCA intermediate in both species. According to
      results, sugars, amino acid and energy metabolism were affected by drought and,
      among them, TCA intermediates had more alternation in two studied species so,
      this cycle and its intermediates probably have more prominent role than other
      identified metabolites in the induction of drought tolerance.

PMID- 30286405
TI  - Toxic effects of the fungicide tebuconazole on the root system of fusarium
      infected wheat plants.
AB  - The study investigates toxic effects of the fungicide tebuconazole (TEB) on
      Fusarium-infected wheat (Triticum aestivum) plants based on the morphological
      characteristics of root apices and changes in the integrated parameters of redox
      homeostasis, including the contents of free proline and products of peroxidation
      of proteins (carbonylated proteins, CP) and lipids (malondialdehyde, MDA) in
      roots. In two-day-old wheat sprouts infected by Fusarium graminearum, the levels
      of proline, CP, and border cells of root apices are higher than in roots of
      uninfected sprouts by a factor of 1.4, 8.0, and 3, respectively. The triazole
      fungicide tebuconazole (TEB) at the concentrations of 0.01, 0.10, and 1.00 MUg ml
      1 of medium causes a dose-dependent decrease in the number of border cells. The
      study of the effects of TEB and fusarium infection on wheat plants in a 30-day
      experiment shows that the effect of the fungicide TEB on redox homeostasis in
      wheat roots varies depending on the plant growth stage and is significantly
      different in ecosystems with soil and plants infected by Fusarium phytopathogens.
      The study of the morphology of root apices shows that the toxic effects of TEB
      and fusarium infection are manifested in the destructive changes in root apices
      and the degradation of the root tip mantle.

PMID- 30286406
TI  - Salinity effect on Cuscuta campestris Yunck. Parasitism on Arabidopsis thaliana
      L.
AB  - Stem holoparasitic flowering plants of the genus Cuscuta are globally distributed
      invasive species and agricultural pests. The present research represents the
      combined effect of salt stress (e.g. abiotic stress) and Cuscuta campestris
      infection (e.g. biotic stress) on the model host plant Arabidopsis thaliana and
      the response of the parasite to salinity. The response of these parasites to
      abiotic stress conditions including salinity is poorly studied. Arabidopsis
      plants were continuously irrigated with 0, 50 and 150 mM NaCl and subjected to C.
      campestris infection. The influence of both abiotic and biotic stresses on the
      major osmoprotectant L-proline and three antioxidant enzymes - catalase,
      superoxide dismutase and guaiacol peroxidase, was assessed in both the parasite
      and the host plant. All four biochemical markers were differentially affected by
      stress, showing that the influence of C. campestris parasitism and its
      interaction with salinity is mostly in the site of infection (direct response)
      and also in roots (indirect vertical response) rather than on non-infected leaves
      of infected plants (indirect horizontal response). Despite its absence of soil
      contact, C. campestris was also significantly affected by salinity (indirect
      response). The mutual adaptation of the parasite-host pair to salinity slightly
      altered the regular response to abiotic stress of A. thaliana, but no detrimental
      additive effect of biotic and abiotic stress was observed.

PMID- 30286407
TI  - Rejuvenation of plasticity in the brain: opening the critical period.
AB  - Cortical circuits are particularly sensitive to incoming sensory information
      during well-defined intervals of postnatal development called 'critical periods'.
      The critical period for cortical plasticity closes in adults, thus restricting
      the brain's ability to indiscriminately store new sensory information. For
      example, children acquire language in an exposure-based manner, whereas learning
      language in adulthood requires more effort and attention. It has been suggested
      that pairing sounds with the activation of neuromodulatory circuits involved in
      attention reopens this critical period. Here, we review two critical period
      hypotheses related to neuromodulation: cortical disinhibition and thalamic
      adenosine. We posit that these mechanisms co-regulate the critical period for
      auditory cortical plasticity. We also discuss ways to reopen this period and
      rejuvenate cortical plasticity in adults.

PMID- 30286408
TI  - The core promoter controls basal and inducible expression of duck retinoic acid
      inducible gene-I (RIG-I).
AB  - Retinoic acid inducible gene-I (RIG-I) is a cytoplasmic RNA sensor for detecting
      a variety of RNA viruses including influenza A viruses. Detection ultimately
      produces Type I interferon (IFN), which stimulates expression of interferon
      stimulated genes (ISGs), including RIG-I itself in a positive feedback loop. The
      structure and function of RIG-I is conserved across phylogeny, despite
      significant protein sequence divergence, however, the promoter sequences do not
      show the expected phylogenetic relationships and it is not known whether they are
      similarly regulated. We previously cloned duck RIG-I and showed it is highly
      induced during influenza A infection consistent with induction by the interferon
      produced. Here, we identified the Pekin duck RIG-I promoter and constructed
      promoter reporter vectors, which we transfected into duck embryonic fibroblasts
      or chicken DF-1 cells and tested in dual luciferase assays. We showed that
      activation of the Mitochondrial Antiviral Signalling (MAVS) pathway using the
      constitutively active N-terminal region of RIG-I or polyinosinic-polycytidylic
      acid (poly I:C) led to stimulation of duck RIG-I promoter activity. Using
      deletion constructs we showed the core promoter lies in the proximal 250
      basepairs, and we identified essential cis-regulatory elements, a GC-box and an
      interferon-sensitive response element (ISRE), responsible for basal and inducible
      expression, respectively. Using mCherry-tagged interferon regulatory factors
      (IRFs) cloned from chickens and ducks, we show overexpression of chIRF7 induced
      the duck RIG-I promoter, and this required the ISRE site. Finally, we also
      demonstrated that overexpressed chIRF7 translocated to the nucleus, which was
      augmented by MAVS activation using RIG-I 2CARD. Our findings demonstrate that RIG
      I expression is induced by chIRF7, in a positive regulatory loop. These studies
      show that the duck RIG-I promoter is appropriately regulated in chicken cells,
      necessary for the potential generation of transgenic chickens expressing RIG-I.

PMID- 30286409
TI  - Sulthiame add-on therapy in children with Lennox-Gastaut syndrome: A study of 44
      patients.
AB  - PURPOSE: The aim of this study was to evaluate efficacy and tolerability of
      sulthiame as an add-on treatment in 44 patients with Lennox-Gastaut syndrome
      (LGS) refractory to other antiepileptic drugs and/or non-pharmacological
      treatment. METHODS: Patients were selected according to the following criteria:
      (1) age 4 years or older, (2) a diagnosis of LGS refractory to at least four
      previous antiepileptic drugs, alone or in combination. Neurologic examinations,
      brain magnetic resonance imaging, and repeated prolonged electroencephalography
      (EEG) or video-EEG studies were performed in all cases. Data on school
      achievements and/or neuropsychological evaluations were obtained during the
      follow-up of 1-3 years. Sulthiame was added in doses ranging from 5 to 30
      mg/kg/day. RESULTS: Twenty-seven of 44 patients (61%) who received sulthiame as
      add-on therapy had a greater than 50% seizure decrease after a mean follow-up
      period of 20 months. Complete seizure freedom was achieved in one patient (2%).
      Four patients (9%) had a 25-50% seizure decrease, while seizure frequency
      remained unchanged in 12 (25%), and was increased in one (2%). Hyperpnoea and
      dyspnoea were observed in four patients, and nausea, drowsiness, and headache
      were seen in one patient each; however, these manifestations were transient and
      discontinuation of sulthiame was not necessary. Two other patients had decreased
      appetite, skin rash, and irritability. The adverse effects were mild and
      transient in these nine cases. CONCLUSION: Sulthiame as an adjunctive therapy
      achieved a more than 50% seizure reduction in 27 of 44 patients with LGS with
      only mild or moderate adverse effects.

PMID- 30286410
TI  - Narrative analysis of written accounts about living with epileptic or psychogenic
      nonepileptic seizures.
AB  - PURPOSE: This study is based on a narrative analysis of individuals' written
      accounts of living with epilepsy (n = 29) or psychogenic non-epileptic seizures
      (n = 20, PNES). Narrative analysis looks at both the content and structure of the
      personal account. We used a form of narrative analysis that allowed us to
      identify common story lines, otherwise known as narrative typologies, potentially
      characteristic of these patient groups. Different narrative typologies were
      described and compared between writers with the two conditions. METHODS: As part
      of a therapeutic writing intervention for individuals living with a seizure
      disorder, participants were asked to write for at least 20 min about their very
      deepest thoughts and feelings about their condition. RESULTS: Five narrative
      typologies emerged: 1. 'Losses from Illness' - stories were dominated by events
      individuals could no longer do, authors appeared more disabled reporting greater
      frequency of seizures and lower health-related quality of life. 2.'Feeling Lost' 
      participants appeared to be in search of something and expressed uncertainty.
      3.'Tackling Adversity' - individuals strove to not let their condition stop them
      from living their life. 4.'Overcoming Challenges' - stories reflected that the
      condition must be battled and fought with. 5.'A Normal Life' - individuals had
      demonstrated that they are managing to live with their condition. CONCLUSIONS:
      While the 'Tackling Adversity' typology was preferentially used by writers with
      epilepsy, the 'Feeling Lost' typology was chosen more commonly by those with
      PNES. People with epilepsy narrate their disorder differently from those with
      PNES, suggesting that they have different life and illness experiences.

PMID- 30286411
TI  - Analysis of microvascular blood flow and oxygenation: Discrimination between two
      haemodynamic steady states using nonlinear measures and multiscale analysis.
AB  - OBJECTIVE: This study investigates the feasibility of the use of nonlinear
      complexity methods as a tool to identify altered microvascular function often
      associated with pathological conditions. We evaluate the efficacy of multiscale
      nonlinear complexity methods to account for the multiple time-scales of processes
      modulating microvascular network perfusion. METHODS: Microvascular blood flux
      (BF) and oxygenation (OXY: oxyHb, deoxyHb, totalHb and SO2%) signals were
      recorded simultaneously at the same site, from the skin of 15 healthy young male
      volunteers using combined laser Doppler fluximetry (LDF) and white light
      spectroscopy. Skin temperature was clamped at 33  degrees C prior to warming to
      43  degrees C to generate a local thermal hyperaemia (LTH). Conventional and
      multiscale variants of sample entropy (SampEn) were used to quantify signal
      regularity and Lempel and Ziv (LZ) and effort to compress (ETC) to determine
      complexity. RESULTS: SampEn showed a decrease in entropy during LTH in BF (p =
      0.007) and oxygenated haemoglobin (oxyHb) (p = 0.029). Complexity analysis using
      LZ and ETC also showed a significant reduction in complexity of BF (LZ, p =
      0.003; ETC, p = 0.002) and oxyHb (p < 0.001, for both) with LTH. Multiscale
      complexity methods were better able to discriminate between haemodynamic states
      (p < 0.001) than conventional ones over multiple time-scales. CONCLUSION: Our
      findings show that there is a good discrimination in complexity of both BF and
      oxyHb signals between two haemodynamic steady states which is consistent across
      multiple scales. SIGNIFICANCE: Complexity-based and multiscale-based analysis of
      BF and OXY signals can identify different microvascular functional states and
      thus has potential for clinical application in the prognosis and the diagnosis of
      pathophysiological conditions such as microvascular dysfunction observed in non
      alcoholic fatty liver disease and type 2 diabetes.

PMID- 30286412
TI  - Visualizing the detection area of a unilateral NMR sensor using deconvolution and
      back-projection.
AB  - Understanding the detection volume of a unilateral NMR sensor is crucial to
      interpret acquired data appropriately. Whereas this is easily done in the
      sensor's axial dimension by running a depth profile on a well-defined sample, the
      lateral dimension is commonly characterized with very small samples, where each
      position along a regular grid is scanned individually, typically resulting in
      measurement times of several days and a resolution that is limited to the
      dimensions of the sample. Here we apply two mathematical procedures known from
      image processing that employ samples larger than the pixel size to characterize
      the lateral detection area. One procedure uses deconvolution algorithms to
      account for blurring effects caused by a larger sample while the other utilizes
      back-projection of radial field profiles. Both approaches are demonstrated with a
      Profile NMR-MOUSE(r) (PM5). They yield field maps in good agreement with those
      acquired with pixel-size test samples but save about one order of magnitude in
      scanning time.

PMID- 30286413
TI  - Real-time J-upscaling in two-dimensional pure shift diagonal NMR: Simultaneous
      resolution enhancement in chemical shifts and scalar couplings.
AB  - A two-dimensional real-time J-upscaled pure shift diagonal pulse scheme, JS
      PSYCHE-DIAG has been developed. This method enhances the resolution in scalar
      coupling multiplets by real-time J-upscaling during the direct acquisition, and
      these J-upscaled multiplets resolve on the diagonal at the respective pure shift
      positions, which results in resolution enhancement in chemical shifts. Thus, both
      chemical shifts and scalar couplings get better resolved simultaneously in the
      same NMR experiment. The efficacy of the present method has been demonstrated,
      (i) on hesperidin for resolving the J-upscaled multiplets belonging to
      diastereomers and (ii) on a natural product, strychnine, to measure small scalar
      couplings including the long range values.

PMID- 30286414
TI  - Temperament traits and remission of depression: A naturalistic six-month
      longitudinal study.
AB  - BACKGROUND: The aim of this naturalistic longitudinal study was to add evidence
      regarding the potential of Cloninger's temperament traits (novelty seeking, harm
      avoidance, reward dependence and persistence) for predicting the effect of
      pharmacological treatment on the rates of therapeutic response and remission.
      METHODS: The study was based on 200 outpatients with unipolar depressive
      disorders of different severity and course of illness, and extended up to 6
      months of follow-up. Patients were assessed in their temperament with the
      Tridimensional Personality Questionnaire (TPQ) and their condition was classified
      (in course and severity) according to the International Classification of
      Diseases, Tenth revision (ICD-10) diagnostic criteria for research. Patients were
      blindly rated (concerning other predicting variables) on the improved Clinical
      Global Impression-Severity scale for depression (iCGI-S) at baseline, 6 weeks, 3
      months and 6 months. Outcome measures at the last observation carried forward
      were therapeutic response (reduction of >=50% in the last iCGI-S) and remission
      (last iCGI-S = 0), which were available for 187 patients. RESULTS: Remission was
      independently and directly associated with length of follow-up, and inversely
      with the baseline iCGI-S score and harm avoidance (patients in the high tertile
      had a 2.7 likelihood of non-remission in comparison with those in the low
      tertile); persistence was found to have a complex, V-shape relationship with
      remission. Within a sub-sample of more severe cases (n = 118), having higher harm
      avoidance scores, a more favorable outcome was associated with higher reward
      dependence and the non-smoking condition. LIMITATIONS: With a naturalistic, non
      experimental design, the sample may not be representative of the general
      population. CONCLUSIONS: Temperament traits may help predict outcome in patients
      treated for depression.

PMID- 30286415
TI  - A systematic meta-review of predictors of antidepressant treatment outcome in
      major depressive disorder.
AB  - INTRODUCTION: The heterogeneity of symptoms and complex etiology of depression
      pose a significant challenge to the personalization of treatment. Meanwhile, the
      current application of generic treatment approaches to patients with vastly
      differing biological and clinical profiles is far from optimal. Here, we conduct
      a meta-review to identify predictors of response to antidepressant therapy in
      order to select robust input features for machine learning models of treatment
      response. These machine learning models will allow us to learn associations
      between patient features and treatment response which have predictive value at
      the individual patient level; this learning can be optimized by selecting high
      quality input features for the model. While current research is difficult to
      directly apply to the clinic, machine learning models built using knowledge
      gleaned from current research may become useful clinical tools. METHODS: The
      EMBASE and MEDLINE/PubMed online databases were searched from January 1996 to
      August 2017, using a combination of MeSH terms and keywords to identify relevant
      literature reviews. We identified a total of 1909 articles, wherein 199 articles
      met our inclusion criteria. RESULTS: An array of genetic, immune, endocrine,
      neuroimaging, sociodemographic, and symptom-based predictors of treatment
      response were extracted, varying widely in clinical utility. LIMITATIONS: Due to
      heterogeneous sample sizes, effect sizes, publication biases, and methodological
      disparities across reviews, we could not accurately assess the strength and
      directionality of every predictor. CONCLUSION: Notwithstanding our cautious
      interpretation of the results, we have identified a multitude of predictors that
      can be used to formulate a priori hypotheses regarding the input features for a
      computational model. We highlight the importance of large-scale research
      initiatives and clinically accessible biomarkers, as well as the need for
      replication studies of current findings. In addition, we provide recommendations
      for future improvement and standardization of research efforts in this field.

PMID- 30286416
TI  - Repeat-dose ketamine augmentation for treatment-resistant depression with chronic
      suicidal ideation: A randomized, double blind, placebo controlled trial.
AB  - BACKGROUND: Several studies indicate that ketamine has rapid antidepressant
      effects in patients with treatment-resistant depression (TRD). The extent to
      which repeated doses of ketamine (versus placebo) reduce depression in the short
      and long term among outpatients with TRD and chronic, current suicidal ideation
      remains unknown. METHODS: Twenty-six medicated outpatients with severe major
      depressive disorder with current, chronic suicidal ideation were randomized in a
      double-blind fashion to six ketamine infusions (0.5 mg/kg over 45 minutes) or
      saline placebo over three weeks. Depression and suicidal ideation were assessed
      at baseline, 240 min post-infusion, and during a three-month follow-up phase.
      RESULTS: During the infusion phase, there was no differences in depression
      severity or suicidal ideation between placebo and ketamine (p = 0.47 and p =
      0.32, respectively). At the end of the infusion phase, two patients in the
      ketamine group and one in the placebo group met criteria for remission of
      depression. At three-month follow-up, two patients in each group met criteria for
      remission from depression. LIMITATIONS: Limitations include the small sample
      size, uncontrolled outpatient medication regimens, and restriction to
      outpatients, which may have resulted in lower levels of suicidal ideation than
      would be seen in emergency or inpatient settings. CONCLUSIONS: Repeated, non
      escalating doses of ketamine did not outperform placebo in this double-blind,
      placebo controlled study of patients with severe TRD and current, chronic
      suicidal ideation. This result may support our previously published open-label
      data that, in this severely and chronically ill outpatient population, the
      commonly used dose of 0.5 mg/kg is not sufficient.

PMID- 30286419
TI  - The effects of sport specific training of rugby players on avoidance behaviours
      during a head-on collision course with an approaching person.
AB  - Individuals use visual information to plan and adapt movements to dynamically
      changing environments. This information is used to accurately determine when and
      where they may come in contact with an object. More specifically, individuals may
      determine the time prior to contacting an object, known as time-to-contact (TTC).
      Sport provides a scenario where athletes compete in dynamically changing
      environments and must interact with opposing players. The effects of sport
      specific training on obstacle avoidance is highly controversial and research
      suggests the quantifiable differences in behaviours compared to non-athletes is
      highly context specific. The current study aimed to examine if sport-specific
      training has an impact on the avoidance behaviours of rugby players during a head
      on collision course with an approaching person. Female rugby players (N = 10, x-
      = 20 +/- 0.94 years) and non-athletes (N = 10, x- = 21.9 +/- 1.6 years) were
      instructed to walk along a 10 m path towards a goal located along the midline. A
      female confederate initially positioned along the midline 180 degrees  from the
      participant walked towards the participant to one of four predetermined final
      positions: 1) along the midline in the participants' starting position; 2)
      stopped along the midline 2.5 m from her starting position; 3) to the left of the
      participants' starting position; and 4) to the right of the participants'
      starting position. Results revealed when the path of the confederate was
      uncertain, individuals used a consistent TTC to determine when to change their
      path. The rugby players in the current study were found to avoid significantly
      later (i.e. smaller TTC) than non-athletes. However, following a change in path,
      sport-specific training did not impact the avoidance behaviours of the groups,
      but rather the environment was the regulating factor. When the path of the
      confederate was uncertain, individuals did not use a single avoidance strategy,
      instead considered the fit between their individual characteristics (i.e., action
      capabilities) and components of the environment (i.e. path of the confederate and
      task constraints). Athletes who are specifically trained to pass through spaces
      and avoid obstacles (i.e., rugby backs) may consider their action capabilities in
      conjunction with their visual information to determine time of avoidance.

PMID- 30286417
TI  - The PanCareSurFup consortium: research and guidelines to improve lives for
      survivors of childhood cancer.
AB  - BACKGROUND: Second malignant neoplasms and cardiotoxicity are among the most
      serious and frequent adverse health outcomes experienced by childhood and
      adolescent cancer survivors (CCSs) and contribute significantly to their
      increased risk of premature mortality. Owing to differences in health-care
      systems, language and culture across the continent, Europe has had limited
      success in establishing multi-country collaborations needed to assemble the
      numbers of survivors required to clarify the health issues arising after
      successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European
      project to evaluate some of the serious long-term health risks faced by
      survivors. This article sets out the overall rationale, methods and preliminary
      results of PCSF. METHODS: The PCSF consortium pooled data from 13 cancer
      registries and hospitals in 12 European countries to evaluate subsequent primary
      malignancies, cardiac disease and late mortality in survivors diagnosed between
      ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of
      second malignancies and to the heart, developed evidence-based guidelines for
      long-term care and for transition services, and disseminated results to survivors
      and the public. RESULTS: We identified 115,596 individuals diagnosed with cancer,
      of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single
      data set forms the basis for cohort analyses of subsequent malignancies, cardiac
      disease and late mortality and case-control studies of subsequent malignancies
      and cardiac disease in 5-year survivors. CONCLUSIONS: PCSF delivered specific
      estimates of risk and comprehensive guidelines to help survivors and care-givers.
      The expected benefit is to provide every European CCS with improved access to
      care and better long-term health.

PMID- 30286420
TI  - Continuous column adsorption of naphthenic acids from synthetic and real oil
      sands process-affected water (OSPW) using carbon-based adsorbents.
AB  - In this study, activated petroleum coke (APC) and commercial activated carbon
      (CAC) were used in a continuous adsorption column for removal of model naphthenic
      acids and organics from real oil sands process-affected water (OSPW).
      Diphenylacetic acid and 2-naphthoic acid, two model naphthenic acid (NA)
      compounds, were removed completely by the APC in a continuous column operation.
      Due to the complex nature of organics in OSPW, total organic carbon (TOC) was
      measured to determine the effectiveness of OSPW treatment by APC. The removal of
      TOC from OSPW at its natural pH 8 by APC was only 25%, whereas acidification at
      pH 4 followed by APC adsorption removed 96% of the initial TOC. When compared to
      a commercial activated carbon, the APC showed an average of 20% higher organics
      removal. The experimental breakthrough curves were better fitted by Thomas model
      in comparison to Adams-Bohart and Yoon-Nelson models. The regeneration of APC was
      conducted using methanol with 0.01 wt% NaOH (pH = 11.7) and a total of four
      cycles of adsorption and regeneration were conducted with marginal loss of
      adsorption sites.

PMID- 30286418
TI  - Results of a multicentre randomised controlled trial of cochlear-sparing
      intensity-modulated radiotherapy versus conventional radiotherapy in patients
      with parotid cancer (COSTAR; CRUK/08/004).
AB  - PURPOSE: About 40-60% of patients treated with post-operative radiotherapy for
      parotid cancer experience ipsilateral sensorineural hearing loss. Intensity
      modulated radiotherapy (IMRT) can reduce radiation dose to the cochlea. COSTAR, a
      phase III trial, investigated the role of cochlear-sparing IMRT (CS-IMRT) in
      reducing hearing loss. METHODS: Patients (pT1-4 N0-3 M0) were randomly assigned
      (1:1) to 3-dimensional conformal radiotherapy (3DCRT) or CS-IMRT by minimisation,
      balancing for centre and radiation dose of 60Gy or 65Gy in 30 daily fractions.
      The primary end-point was proportion of patients with sensorineural hearing loss
      in the ipsilateral cochlea of >=10 dB bone conduction at 4000 Hz 12 months after
      radiotherapy compared using Fisher's exact test. Secondary end-points included
      hearing loss at 6 and 24 months, balance assessment, acute and late toxicity,
      patient-reported quality of life, time to recurrence and survival. RESULTS: From
      Aug 2008 to Feb 2013, 110 patients (54 3DCRT; 56 CS-IMRT) were enrolled from 22
      UK centres. Median doses to the ipsilateral cochlea were 3DCRT: 56.2Gy and CS
      IMRT: 35.7Gy (p < 0.0001). 67/110 (61%) patients were evaluable for the primary
      end-point; main reasons for non-evaluability were non-attendance at follow-up or
      incomplete audiology assessment. At 12 months, 14/36 (39%) 3DCRT and 11/31 (36%)
      CS-IMRT patients had >=10 dB loss (p = 0.81). No statistically significant
      differences were observed in hearing loss at 6 or 24 months or in other secondary
      end-points including patient-reported hearing outcomes. CONCLUSION: CS-IMRT
      reduced the radiation dose below the accepted tolerance of the cochlea, but this
      did not lead to a reduction in the proportion of patients with clinically
      relevant hearing loss.

PMID- 30286421
TI  - Photodegradation of fluazaindolizine in water under simulated sunlight
      irradiation: Identification of transformation products and elucidation of
      transformation mechanism.
AB  - The photodegradation of fluazaindolizine in water was investigated under
      simulated sunlight irradiation. The effects of solution pH, humic acids (HA),
      nitrates (NO3-) and Fe(III) ions on photolysis of fluazaindolizine were studied.
      The results indicated that pH did not significantly affect its photodegradation.
      At low concentration (up to 5 mg/L), HA slightly facilitated the photodegradation
      of fluazaindolizine, while at high concentration (10-20 mg/L), HA inhibited its
      photodegradation. The presence of NO3- (0-10 mg/L) and Fe(III) (0-5 mg/L)
      noticeably accelerated the photodegradation of fluazaindolizine. Moreover, eleven
      direct transformation products (TPs) were isolated and identified by liquid
      chromatography quadrupole time-of-flight mass spectrometry. Density functional
      theory (DFT) calculation was utilized to characterize molecular property of
      fluazaindolizine and predict the potentiality of the possible photodegradation
      reaction. Ultimately, a possible transformation mechanism was proposed based on
      the identified TPs, degradation profiles and DFT calculation. The predominant
      photoproduct came from ring opening of imidazole-ring and dechlorination. Other
      TPs resulted from a series of photochemical reactions involving hydroxyl
      substitution, ring-opening, cleavage, oxidation and decarboxylation. These
      results were important in elucidating environmental fate of fluazaindolizine in
      aquatic system and further environmental risk assessment.

PMID- 30286422
TI  - Promotional effect of doping Cu into cerium-titanium binary oxides catalyst for
      deep oxidation of gaseous dichloromethane.
AB  - In recent years, significant effort has been made in the development of novel
      catalysts for the total oxidation of chlorinated volatile organic compounds. In
      this work the catalytic activity of Cu doped cerium-titanium binary oxides for
      the oxidation of dichloromethane (DCM) have been studied for the first time.
      Combining catalysts characterization and activity data, it was found that Cu ions
      can uniformly disperse into titanium dioxide to form solid solution and induce
      the creation of additional surface oxygen species on the catalysts surface, while
      moderate amount of Ce ions are still needed for the activation of CCl. Detailed
      analysis of the in-situ FTIR experiment results revealed that the surface oxygen
      species, especially the hydroxyl groups associated with Cu ions, can promote the
      deep oxidation of the intermediate species formed in the nucleophilic
      substitution process occurred on the active sites of catalysts surface. The
      sample with the Cu/Ce molar ratio of 1:3 obtained a better CO2 selectivity than
      that reached with cerium-titanium binary oxides. Meanwhile, according to element
      balance analysis, removal of chlorine from the catalyst surface was also promoted
      by Cu doping.

PMID- 30286423
TI  - Synergism and antagonisms between nutrients induced by copper toxicity in
      grapevine rootstocks: Monocropping vs. intercropping.
AB  - The long-term use of Cu-containing fungicides contaminates vineyards soils, which
      can induce Cu toxicity and nutrient imbalances in several plant species. The aim
      of this work was to evaluate the effect of Cu toxicity on two grapevine
      rootstocks, Fercal and 196.17, and to elucidate if intercropping with oat can
      alleviate grapevine Cu toxicity. Plants were hydroponically-cultivated and
      treated with different Cu concentrations. At harvest the biomass accumulation,
      the SPAD index and the symplastic and apoplastic root and leaves ionome were
      measured to evaluate possible synergistic and/or antagonistic effects on other
      micro- and macronutrients. The root exudation analysis was correlated with genes
      expression (VvPEZ-like), whereas PCA analysis performed on the grapevine and oat
      ionome revealed that both mono- and intercropped 196.17 rootstock display a
      positive effect on Zn and Mn in the root tissues at high Cu concentrations. An
      increase of Zn and Mn in roots was also reported for the intercropped Fercal
      rootstock at high Cu concentrations while an antagonistic relation was reported
      for root Zn concentration in the monocropped Fercal rootstock. Our results showed
      that grapevine and oat compete for nutrient uptake and that this phenomenon can
      possibly alleviate grapevine Cu toxicity. However, Fercal rootstock is able to
      take advantage from oat, while 196.17 is disadvantaged by the intercropping
      system. Even though intercropping system seems to be a valuable tool to
      counteract grapevine Cu toxicity, the application of this agricultural practice
      has shown to be species dependent and should be evaluated for each rootstock.

PMID- 30286424
TI  - Effects of different concentrations of Microcystis aeruginosa on the intestinal
      microbiota and immunity of zebrafish (Danio rerio).
AB  - Microcystis aeruginosa is a primary species of toxin-producing cyanobacteria.
      This study explored the effects of short-term exposure (96 h) to M. aeruginosa on
      the intestinal microflora variation and immune function of zebrafish. After
      exposure to different cell concentrations of M. aeruginosa, marked histological
      variation was observed in the intestine, such as goblet cells proliferation and
      intestinal desquamation. In addition high-concentration M. aeruginosa treatment
      (initial concentration: 1.59 * 105 cells mL-1) induced a significant increase in
      cytokine levels compared with other groups. Low-concentration M. aeruginosa
      treatment (initial concentration: 0.88 * 105 cells mL-1) promoted the
      transcription of inflammatory genes, while high-concentration treatment
      restrained the transcription of these genes. Moreover, M. aeruginosa exposure
      also changed the intestinal microbial diversity. At the phylum level, bacteria
      belonging to Proteobacteria were the most abundant in all groups, and
      Gammaproteobacteria were the dominant bacteria with major changes. Pathogenic
      microorganisms such as Shewanella, Plesiomonas, Halomonas, Pseudomonas, and
      Lactobacillus increased greatly after treatment with different cell
      concentrations of M. aeruginosa. This study indicates that M. aeruginosa induces
      an increase in zebrafish goblet cells and enhances the inflammatory response,
      which may produce detrimental effects in zebrafish, resulting in a greater
      proportion of pathogenic bacteria and intestinal injury. The results of this
      study will help improve the understanding of the effects of M. aeruginosa on the
      intestines of aquatic organisms.

PMID- 30286426
TI  - Indoor air pollution and exposure assessment of the gulf cooperation council
      countries: A critical review.
AB  - Indoor air pollution is one of the human health threat problems in the Gulf
      Cooperation Council (GCC) countries. In these countries, due to unfavorable
      meteorological conditions, such as elevated ambient temperature, high relative
      humidity, and natural events such as dust storms, people spend a substantial
      amount of their time in indoor environments. In addition, production of physical
      and biological aerosols from air conditioners, cooking activities, burning of
      Arabian incense, and overcrowding due to pilgrimage programs are common causes of
      low quality indoor air in this region. Thus, due to infiltration of outdoor
      sources as well as various indoor sources, people living in the GCC countries are
      highly exposed to indoor air pollutants. Inhalation of indoor air pollutants
      causes mortalities and morbidities attributed to cardiorespiratory, pulmonary,
      and lung cancer diseases. Hence, the aim of this review study is to provide a
      summary of the major findings of indoor air pollution studies in different
      microenvironments in six GCC countries. These include characterization of
      detected indoor air pollutants, exposure concentration levels, source
      identifications, sustainable building designs and ventilation systems, and the
      mitigation strategies. To do so, >130 relevant indoor air pollution studies
      across the GCC countries were critically reviewed. Particulate matters (PM10 and
      PM2.5), total volatile organic compounds (TVOCs), carbon dioxide (CO2), sulfur
      dioxide (SO2), nitrogen dioxide (NO2), and heavy metals were identified as the
      reported indoor air pollutants. Apart from them, indoor Radon and bioaerosols
      were studied only in specific GCC countries. Thus, future studies should also
      focus on the investigation of emerging indoor air pollutants, such as ultrafine
      and nanoparticles and their associated health effects. Furthermore, studies on
      the mitigation of indoor air pollution through the development of advanced air
      purification and ventilation systems could improve the indoor air quality (IAQ)
      in the GCC region.

PMID- 30286425
TI  - Monitoring WWTP performance using size-exclusion chromatography with simultaneous
      UV and fluorescence detection to track recalcitrant wastewater fractions.
AB  - A trial monitoring of a typical full-scale municipal WWTP in Central Finland was
      aimed to explore applicability of high performance liquid chromatography - size
      exclusion chromatography (HPSEC) with simultaneous UV and fluorescence detection
      as a tool for advanced routine monitoring of wastewater treatment. High,
      intermediate, and low molecular weight (MW) fractions of untreated wastewater
      (influent) and treated wastewater (secondary effluent) were characterized in
      terms of UV absorbance at 254 nm (UVA254) and specific fluorescence representing
      tyrosine-like, tryptophan-like, and humic/fulvic-like compounds. The activated
      sludge treatment removed 97 +/- 1% of BOD, 93 +/- 2% of COD, 71 +/- 7% of DOC,
      and 24 +/- 7% of TN, while the overall reduction of UVA254 was 50 +/- 6%. Total
      fluorescence signal declined by ~80% for tyrosine-like, by 60-70% for tryptophan
      like, and by 7-36% for humic/fulvic-like compounds. Low and intermediate MW
      humic/fulvic-like compounds fluorescing at lambdaex/lambdaem = 390/500 nm
      demonstrated recalcitrant behavior. Protein-like and humic/fulvic-like fractions
      of low MW < 1 kDa accounted for 60-65% of total UVA254 and 50-70% of total
      fluorescence of whole influent and effluent samples. Strong linear correlations
      were observed between wastewater BOD, COD, DOC, UVA254 and tyrosine-like,
      tryptophan-like fluorescence.

PMID- 30286427
TI  - Insertion position as well as the inserted TRS and gene sequences differentially
      affect the retention of foreign gene expression by simian hemorrhagic fever virus
      (SHFV).
AB  - Recombinant SHFV infectious cDNA clones expressing a foreign gene from an
      additional sg mRNA were constructed. Two 3' genomic region sites, between ORF4'
      and ORF2b and between ORF4 and ORF5, were utilized for insertion of the myxoma
      M013 gene with a C-terminal V5 tag followed by one of the three inserted
      transcription regulatory sequences (TRS), TRS2', TRS4' or TRS7. M013 insertion at
      the ORF4'/ORF2b site but not the ORF4/ORF5 site generated progeny virus but only
      the recombinant virus with an inserted TRS2' retained the entire M013 gene
      through passage four. Insertion of an auto-fluorescent protein gene, iLOV, with
      an inserted TRS2' at the ORF4'/ORF2b site, generated viable progeny virus. iLOV
      expression was maintained through passage eight. Although regulation of SHFV
      subgenomic RNA synthesis is complex, the ORF4'/ORF2b site, which is located
      between the two sets of minor structural proteins, is able to tolerate foreign
      gene insertion.

PMID- 30286428
TI  - Magnitude processing of written number words is influenced by task, rather than
      notation.
AB  - The extent to which task and notation influence the processing of numerical
      magnitude is under theoretical and empirical debate. To date, behavioural studies
      have yielded a mixed body of evidence. Using the case of written number words in
      English and Chinese, we re-examined this issue. Thirty-nine bilingual
      participants who showed a balanced profile of language dominance in English and
      Chinese completed three tasks of numerical processing (Magnitude Comparison,
      Numerical Matching, and Language Matching) with pure English, pure Chinese, and
      mixed notation number words. We conducted frequentist and Bayesian statistics on
      the data. Magnitude processing, as indexed by the numerical distance effect
      (NDE), was found to be dependent on task. Specifically, the NDE occurred in all
      notation conditions in the Magnitude Comparison Task and mixed notation trials in
      the Numerical Matching Task only. However, the data indicated that magnitude
      processing was independent of notation. Task and notation had an interactive
      influence on overall speed of processing, where participants responded to Chinese
      number words significantly faster than other notations for the Magnitude
      Comparison and Numerical Matching Tasks only. Finally, Bayesian analyses
      indicated that task and notation do not interact to affect magnitude processing.
      Specifically, the Bayes Factor and posterior model probabilities of the Bayesian
      ANOVA yielded strongest support for the model with three main effects (Task,
      Notation, Numerical Distance) and two two-way interactions (Task * Numerical
      Distance, Task * Notation). These findings highlight the critical role of task in
      numerical magnitude processing, provide support for a notation-independent
      account of magnitude processing, and suggest that linguistic/orthographic
      factors, combined with task, may interact to affect overall speed of processing.

PMID- 30286429
TI  - Differential inter-trial effects in the visual search of children, adolescents,
      and young adults.
AB  - We examined the age-related variation in one type of inter-trial effect of visual
      search, the distractor previewing effect (DPE), in affectively neutral and
      affectively charged contexts. In Experiment 1, children, adolescents, and young
      adults were faster to identify the shape of a color target when the color of the
      current distractors had already been previewed than when the target had been
      previewed in the preceding target-absent trial, indicative of a color-based DPE.
      The results revealed a greater DPE in children than in adolescents and young
      adults, but it can be attributed to children's slower RTs than the other two
      groups. In Experiment 2, children, adolescents, and young adults were instructed
      to respond to a schematic face that was different from the other two faces. Young
      adults were faster in searching for a threatening face among friendly ones when
      they had previewed a target-absent display consisting of friendly faces than that
      of threatening faces, indicating an emotional DPE. By contrast, children showed a
      reversed DPE under the same condition, whereas adolescents showed no DPE. Taken
      together, these results suggested that the three age groups were all able to
      create an inhibitory attentional bias on the basis of trial history in
      affectively neutral context, whereas children and adolescents were not able to
      create such an inhibitory attentional bias in affectively charged contexts in the
      same way as adults did. These findings implied that the development of
      attentional inhibition abilities in affectively charged contexts might be delayed
      compared to those in affectively neutral contexts.

PMID- 30286430
TI  - EGR1 is essential for deoxynivalenol-induced G2/M cell cycle arrest in HepG2
      cells via the ATF3DeltaZip2a/2b-EGR1-p21 pathway.
AB  - Deoxynivalenol (DON) is a type B trichothecene mycotoxin that exerts multiple
      toxic effects on plants, animals and humans. Several reports have shown that DON
      leads to G2/M cell cycle arrest. However, its molecular mechanism is still
      unclear. In this study, we showed that DON induced strong G2/M cell cycle arrest
      in HepG2 cells, and the cell cycle-inhibitory protein p21 was highly upregulated
      by DON. Further analysis showed that the cell cycle regulating gene EGR1 was
      highly induced by DON and that EGR1 knockdown abolished the upregulation of p21
      and G2/M cell cycle arrest. Furthermore, we showed that the induction of EGR1 was
      regulated by the stress-responsive transcription factor ATF3. ATF3DeltaZip2a/2b,
      which is a DNA binding domain truncated isoform of ATF3, was upregulated by DON.
      ATF3 knockdown weakened the expression induction of EGR1 and G2/M cell cycle
      arrest by DON. Moreover, the upregulation of ATF3DeltaZip2a/2 highly depended on
      the enhanced presence of histones H3K9ac and H3K27ac. H3K9ac and H3K27ac were
      enriched at the promoter region of ATF3 following the DON treatment, and the
      knocking down of the genes responsible for H3K9ac and H3K27ac abolished the
      upregulation of ATF3 by DON. In summary, we found that DON induced G2/M cell
      cycle arrest by sequentially inducing the expression of ATF3DeltaZip2a/2b, EGR1
      and p21, and EGR1 played an essential role in this process, which is a novel
      molecular mechanism of cell cycle arrest by DON and is important for
      understanding its toxicology.

PMID- 30286431
TI  - Fluorinated CdSe/ZnS quantum dots: Interactions with cell membrane.
AB  - Fluorescent inorganic quantum dots are highly promising for biomedical
      applications as sensing and imaging agents. However, the low internalization of
      the quantum dots, as well as for most of the nanoparticles, by living cells is a
      critical issue which should be solved for success in translational research. In
      order to increase the internalization rate of inorganic CdSe/ZnS quantum dots,
      they were functionalized with a fluorinated organic ligand. The fluorinated
      quantum dots displayed an enhanced surface activity, leading to a significant
      cell uptake as demonstrated by in vitro experiments with HeLa cells. We combined
      the experimental and computational results of Langmuir monolayers of the DPPC
      phospholipid as a model cell membrane with in vitro experiments for analyzing the
      mechanism of internalization of the fluorinated CdSe/ZnS quantum dots. Surface
      pressure-molecular area isotherms suggested that the physical state of the DPPC
      molecules was greatly affected by the quantum dots. UV-vis reflection
      spectroscopy and Brewster Angle Microscopy as in situ experimental techniques
      further confirmed the significant surface concentration of quantum dots. The
      disruption of the ordering of the DPPC molecules was assessed. Computer
      simulations offered detailed insights in the interaction between the quantum dots
      and the phospholipid, pointing to a significant modification of the physical
      state of the hydrophobic region of the phospholipid molecules. This phenomenon
      appeared as the most relevant step in the internalization mechanism of the
      fluorinated quantum dots by cells. Thus, this work sheds light on the role of
      fluorine on the surface of inorganic nanoparticles for enhancing their cellular
      uptake.

PMID- 30286432
TI  - LncRNAs on guard.
AB  - Long noncoding RNAs (lncRNAs) are emerging as crucial regulators of gene
      expression in immune system. It has been reported that lncRNAs participate in
      regulation of immune responses through both transcriptional and post
      transcriptional mechanisms. In this review, we summarize the molecular functions
      of lncRNAs and discuss their binding to DNA, RNA and protein targets. We focus on
      the regulatory function of lncRNAs in both innate and adaptive immunity, as well
      as in autoimmunity and cancer immunology. In addition, we point out the
      limitation in current knowledge and future directions for the study of lncRNAs in
      the immune system.

PMID- 30286433
TI  - Association between residential self-selection and non-residential built
      environment exposures.
AB  - Studies employing 'activity space' measures of the built environment do not
      always account for how individuals self-select into different residential and non
      residential environments when testing associations with physical activity. To
      date, no study has examined whether preferences for walkable residential
      neighborhoods predict exposure to other walkable neighborhoods in non-residential
      activity spaces. Using a sample of 9783 university students from Toronto, Canada,
      we assessed how self-reported preferences for a walkable neighborhood predicted
      their exposure to other walkable, non-residential environments, and further
      whether these preferences confounded observed walkability-physical activity
      associations. We found that residential walkability preferences and non
      residential walkability were significant associated (beta = 0.42, 95% CI: (0.37,
      0.47)), and further that these preferences confounded associations between non
      residential walkability exposure and time spent walking (reduction in association
      = 10.5%). These results suggest that self-selection factors affect studies of non
      residential built environment exposures.

PMID- 30286434
TI  - Geographic variation in the impact of a type 2 diabetes diagnosis on behavioural
      change: A longitudinal study using random effects within-between (REWB) models.
AB  - A type 2 diabetes (T2DM) diagnosis has been referred to as a "wake-up call", but
      subsequent behavioural change may be influenced by place of residence. Random
      effects within-between regressions were applied to 130,926 participants in the 45
      and Up Study. T2DM diagnoses effected change in the odds of short sleeps and
      meeting vegetable and alcohol consumption guidelines, but not changes in physical
      activity. Each of these behaviours varied geographically and were patterned by
      area disadvantage and geographic remoteness. Impacts of T2DM diagnosis on
      behavioural change were not found to be geographically contingent, though
      analysis of specific environmental attributes is warranted.

PMID- 30286435
TI  - New insights into phenol and polyphenol composition of Stevia rebaudiana leaves.
AB  - The diversity in phenols and polyphenols of stevia leaf has been simplified
      applying sequential fractionation techniques on its ethanol extract through
      ultrasound assisted maceration. Two of the fractions obtained by reverse-phase
      column chromatography resulted differently active in an extensive antioxidant and
      cytotoxic screening. Both fractions were chemically profiled by ultra-performance
      liquid chromatography (UHPLC) coupled with electrospray ionization (ESI)
      quadrupole/time-of-flight (QqTOF) mass spectrometry (MS). One of the fractions
      was composed mainly of chlorogenic acids and flavonol triglycosides, whereas the
      other was rich in flavonoids mono- and diglycosides and in their hydroxycinnamoyl
      derivatives. Among the fifty compounds identified, non-phenol metabolites, such
      as benzyl primeveroside and roseoside, as well as a lignan polyphenol (5'), are
      reported for the first time as constituents of the Stevia leaf.

PMID- 30286436
TI  - Determination of inorganic anions in the whole blood by ion chromatography.
AB  - A fast, precise, and accurate method that can simultaneously determine 7 anions
      in whole blood was established by on line dialysis-double suppression ion
      chromatography. Performance parameters which could affect the determination of
      anions were optimized, including the selection of protein precipitant in samples,
      the amount of filtrate discarded, selection of eluent flow rate, influence of the
      Ag-Na column on experimental results, influence of ethylenediamines on ClO2-, and
      investigation of nitrogen drying. Finally, 3.6 mmol/L sodium carbonate was
      selected as eluent, with a flow rate of 0.8 mL/min, to separate the 7 anions.
      Blood and alcohol (v/v, 1:4) were used to precipitate the proteins in blood. The
      7 anions reached an adequate recovery rate when the first 2 mL of filtrate from
      the C18 column was discarded. The recovery rate at LLOQ, low, medium, and high
      concentrations was 80-120%. The correlation coefficients (r2) of the calibration
      curves of the targeted anions ranged from 0.9975 to 0.9998. The limit of
      detection (LOD) was 0.309-7.71 MUg/L. This method has simple pretreatment, high
      accuracy, and good reproducibility and selectivity, and is suitable for the
      separation and determination of anions in blood.

PMID- 30286437
TI  - 1H NMR-based dynamic metabolomics delineates the therapeutic effects of Baoyuan
      decoction on isoproterenol-induced cardiac hypertrophy.
AB  - Cardiac hypertrophy (CH) is a major risk factor for many serious heart diseases.
      Sustained CH is catastrophic, resulting in cardiac dysfunction that eventually
      leads to heart failure (HF). Baoyuan decoction (BYD) is a famous traditional
      Chinese medicine (TCM) formula for supplementing and reinforcing Qi, clinically
      used for the treatment of cardiovascular diseases (CVDs). However, the
      therapeutic effects of BYD on CH remain unidentified. We herein investigated the
      effect of BYD on isoproterenol (ISO)-induced CH in rats and the underlying
      mechanisms by comprehensive pharmacodynamics and 1H NMR-based dynamic
      metabolomics analysis of the plasma and urine samples. Results showed that BYD
      treatment markedly attenuated ISO-induced CH as evidenced by decreasing the left
      ventricular wall thickness, pathological cardiomyocyte hypertrophy, myocardial
      collagen fiber deposition and apoptosis, and plasma natriuretic peptide levels.
      Multivariate trajectory analysis revealed that the BYD treatment could restore
      the CH-disturbed plasma and urinary metabolite profiles towards the normal
      metabolic status featuring with a time-dependent tendency. Moreover, the key
      metabolic alterations in CH rats at different BYD-treated time stages involved
      energy metabolism, oxidative stress responses, amino acid metabolism, and gut
      microbiota metabolism. Of particularly, the significant roles of BYD for treating
      CH lie in the improvement of cardiac energy generation and antioxidant capacity.
      Our investigation provides a holistic view of BYD for therapeutic intervention of
      CH through monitoring of the dynamic metabolic changes and the results indicate
      that BYD may be applied as a potential agent for treating CH.

PMID- 30286438
TI  - Extensive characterization and differential analysis of endogenous peptides from
      Bombyx batryticatus using mass spectrometric approach.
AB  - Bombyx batryticatus, the dried larva of Bombyx mori L. (4th-5th instars) infected
      with Beauveria bassiana Vuill, is an important animal-derived medicine effective
      against several diseases. The metamorphosis of silkworm can result insignificant
      changes in the levels of proteins and polypeptides in the 4th and 5th instar
      larvae. Here, we performed extensive characterization of Bombyx batryticatus
      peptides, including polypeptides containing cysteines, using an MS-based data
      mining strategy. A total of 779 peptides with various PTMs (post-translational
      modifications) were identified through database search and de novo sequencing.
      Some of these peptides might have important biological activities. Besides, the
      differential analysis of polypeptides between the head and body of Bombyx
      batryticatus was performed to provide a clinical basis for rational use of the
      drugs derived from it. This study illustrates the abundance and sequences of
      endogenous Bombyx batryticatus polypeptides, and thus, provides potential
      candidates for the screening of active compounds for future biological research
      and drug discovery studies.

PMID- 30286439
TI  - Interactions of pharmacokinetic profiles of Ginkgotoxin and Ginkgolic acids in
      rat plasma after oral administration.
AB  - Ginkgolic acids (GAs) and Ginkgotoxin (4'-O-methylpyridoxine, MPN) are main toxic
      compounds in Ginkgo biloba seeds which are widely used in the treatment of
      coughing in China. To evaluate the pharmacokinetics of GAs, MPN and their
      metabolites in rat plasma, a highly sensitive method followed by ultra-high
      pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass
      spectrometry (UHPLC-LTQ-Orbitrap-MS) has been developed and validated. The
      proposed method is selective, precise and accurate enough of MPN and its
      metabolites (4-pyridoxic Acid, pyridoxal, and pyridoxine) for the pharmacokinetic
      study. After oral administration of MPN, the plasma concentrations of MPN and its
      metabolites were increased rapidly. Meanwhile, an investigation was carried out
      to compare the interactions of the pharmacokinetic profiles of MPN and GAs. Five
      GAs and main metabolites of GA (15:1) and GA (17:1) were also analyzed by using
      our previous method. After coadministration GAs with MPN, Tmax of MPN delayed and
      Cmax decreased. Meanwhile, Tmax of 4-pyridoxic Acid, pyridoxal, and pyridoxine
      were also showed a certain degree of delay. The concentrations of hydroxylation
      products of GA (15:1) and GA (17:1) increased at a slower rate and the area under
      the curves was significantly reduced. However, glucuronidation metabolites of GA
      (15:1) and GA (17:1) were increased faster than administered of GAs alone. The
      interactions of the pharmacokinetic profiles of GAs and MPN in rat plasma after
      oral administration were obviously observed.

PMID- 30286440
TI  - Ionic liquid-based salt-induced liquid-liquid extraction of polyphenols and
      anthraquinones in Polygonum cuspidatum.
AB  - Ionic liquid-based salt-induced liquid-liquid extraction was developed for the
      first time and applied to the extraction of four active constituents, including
      polydatin, resveratrol, emodin, and physcion in Polygonum cuspidatum (P.
      cuspidatum). In this study, ionic liquid was used as extraction solvent. The
      dried P. cuspidatum samples purchased from the pharmacy were triturated and
      passed through a 120-mesh sieve. The obtained sample powders were dried to
      constant weight at 55 C, and then mixed with extraction solvent. The extraction
      was carried out with the aid of ultrasound. Three phases, including ionic liquid
      rich, salt-rich and solid sample phases were formed in the presence of salt. The
      target analytes were enriched in ionic liquid phase and then determined by high
      performance liquid chromatography. The experimental parameters, such as type and
      volume of ionic liquid, type and amount of salt, pH value of extraction medium,
      ultrasound power, ultrasound time and centrifugal condition, were optimized. The
      calibration curves showed good linear relationship (r > 0.9994). The limits of
      detection and quantification were in the range of 2.8-29.5 and 9.4-98.3 ng mL-1,
      respectively. The spiked recoveries were between 92.16% and 105.41%. Compared
      with hot reflux extraction and ultrasound-assisted extraction, the proposed
      method requires less extraction solvent and time. The present method can be
      applied to the determination of polyphenols and anthraquinones in P. cuspidatum.

PMID- 30286441
TI  - Targeting the hot spot in a patient with essential tremor and Parkinson's
      disease: Tractography matters.
AB  - INTRODUCTION: Thalamic ventralis intermedius deep brain stimulation (VIM-DBS) is
      generally effective in treating refractory tremor in Parkinson's disease (PD) and
      in essential tremor (ET), but some patients do not respond well due to side
      effects or from loss of the effect of stimulation over time. The caudal zona
      incerta (ZI) has emerged as a promising target in ET, and the effects of ZI-DBS
      on PD tremor are less studied. Here, we describe a rare situation in which both
      ET and PD coexist in a 72-year-old male referred for ZI-DBS due to refractory
      tremor. The aim of this study was to evaluate whether there was a difference in
      the area stimulated to improve each type of tremor and whether tractography could
      improve and predict motor outcome. METHODS: Two months after the surgery, in
      order to define which of the cathodes was the most effective towards improving
      the tremor and parkinsonian symptoms, a double-blinded, monopolar evaluation was
      conducted on both hemispheres separately. Once the best contact and parameters
      were defined, the volume of tissue activation (VTA) was represented spatially for
      each type of tremor and, finally, the image model was fused with the
      tractography. RESULTS: For both types of tremor, the hot spot stimulated region
      achieved the dentato-rubro-thalamic tract (DRTT) at the higher fiber density
      region. The DRTT fibers were asymmetrical between the right and left hemispheres.
      CONCLUSION: Regardless of the type of tremor, DRTT can be the most effective
      region for stimulation. Tractography should be considered when planning the
      surgical target since the DRTT is not always symmetrical, and the reconstruction
      of the VTA together with the tractography can greatly improve the DBS
      programming, and, probably, the patient's outcome to the stimulation.

PMID- 30286442
TI  - Reprogramming of mitochondrial metabolism by innate immunity.
AB  - The reprogramming of cellular metabolism has emerged as a major aspect of innate
      immune cell activation. Mitochondria, which are well known for their critical
      functions in cellular bioenergetics and metabolism, also serve innate immune
      purposes by providing specific signaling platforms. Latest advances in our
      understanding of innate immune receptor-mediated metabolic reprogramming have
      unraveled specific immune functions of mitochondrial metabolites that place
      mitochondrial metabolism and particularly the mitochondrial respiratory chain at
      the center of innate immunity. This review highlights some recent studies that
      support mitochondrial metabolism as major immune signaling rheostat upon microbe
      recognition by innate immune cells.

PMID- 30286443
TI  - Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: A
      randomized, double-blind, controlled trial.
AB  - RATIONALE: Treatment with a highly purified oral solution of cannabidiol (CBD),
      derived from the plant Cannabis sativa L., demonstrated some evidence of central
      nervous system (CNS)-related adverse events in patients enrolled in phase 3
      trials for treatment of childhood-onset epilepsy. Cannabidiol was categorized as
      a Schedule 1 substance by the United States Drug Enforcement Administration;
      therefore, it was important to test CBD for human abuse potential. METHODS: This
      was a single-dose, randomized, double-blind, double-dummy, placebo- and active
      controlled crossover trial. The abuse potential of single oral doses of plant
      derived pharmaceutical formulations of highly purified CBD (Epidiolex(r); 750 mg,
      1500 mg, and 4500 mg) was compared with that of single oral doses of alprazolam
      (2 mg), dronabinol (10 mg and 30 mg), and placebo in healthy recreational
      polydrug users. The primary endpoint to assess abuse potential was the maximum
      effect (Emax) on Drug-Liking visual analog scale (VAS). Other measurements
      included Emax on Overall Drug-Liking VAS, Take Drug Again VAS, positive and
      negative effects, other subjective effects, and Drug Similarity VAS. Cognitive
      and psychomotor functions were assessed using the Divided Attention Test, the
      Hopkins Verbal Learning Test-Revised, and the Digit-Symbol Substitution Task.
      Pharmacokinetic parameters were determined for CBD and its major metabolites.
      Standard safety measures and adverse events were assessed. PRINCIPAL RESULTS: Of
      95 eligible subjects, 43 qualified for the treatment phase, received at least 1
      dose of investigational medicinal product, and were included in safety
      assessments; 35 subjects were included in the pharmacodynamic analysis. Subjects
      receiving alprazolam and dronabinol had significantly higher Drug-Liking Emax (P
      < 0.0001) compared with those receiving placebo, confirming study validity.
      Compared with placebo, Drug-Liking was not significantly different for subjects
      taking 750-mg CBD (P = 0.51). Drug-Liking Emax values for 1500-mg and 4500-mg CBD
      were significantly different from placebo (P = 0.04 and 0.002, respectively);
      however, the mean differences were <10 points on VAS compared with >18-point
      differences between positive controls and placebo. Alprazolam and dronabinol had
      significantly higher Drug-Liking, Overall-Liking, and Take Drug Again VAS Emax
      values compared with all doses of CBD (P <= 0.004). In contrast to alprazolam,
      CBD administration had no observable effect on cognitive/psychomotor tests.
      Pharmacokinetic parameters for CBD in this trial were consistent with previous
      studies. The majority of adverse events reported during the trial were of mild or
      moderate severity; no serious adverse events or deaths were reported. CONCLUSION:
      Administration of a therapeutic dose of CBD (750 mg) showed significantly low
      abuse potential in a highly sensitive population of polydrug users. Although high
      and supratherapeutic doses of CBD (1500 mg and 4500 mg, respectively) had
      detectable subjective effects compared with placebo; the effects were
      significantly lower than those observed with alprazolam and dronabinol.

PMID- 30286444
TI  - Editorial overview: Recent progress in analytical technologies for design-build
      test-learn cycle in biotechnology.

PMID- 30286446
TI  - Bronchoscopic Lung Volume Reduction Treatment Using Endobronchial Valves for
      Emphysema: Emerging Questions.

PMID- 30286447
TI  - The Gut Microbiota and Hematopoietic Stem Cell Transplantation: Challenges and
      Potentials.
AB  - The human gut microbiota gained tremendous importance in the last decade as next
      generation technologies of sequencing and multiomics analyses linked the role of
      the microbial communities to host physiology and pathophysiology. A growing
      number of human pathologies and diseases are linked to the gut microbiota. One of
      the main mechanisms by which the microbiota influences the host is through its
      interactions with the host immune system. These interactions with both innate and
      adaptive host intestinal and extraintestinal immunity, although usually
      commensalistic even mutualistic with the host, in some cases lead to serious
      health effects. In the case of allogenic hematopoietic stem cell transplantation
      (allo-HSCT), the disruption of the intestinal microbiota diversity is associated
      with acute graft-versus-host disease (GvHD). Causing inflammation of the liver,
      skin, lungs, and the intestine, GvHD occurs in 40-50% of patients undergoing allo
      HSCT and results in significant posttransplantation mortality. In this review, we
      highlight the impact of the gut microbiota on the host immunity in GvHD and the
      potential of microbiota in alleviation or even prevention of GvHD.

PMID- 30286445
TI  - Racial discrimination, educational attainment, and biological dysregulation among
      midlife African American women.
AB  - OBJECTIVE: To examine the association between self-reported racial discrimination
      and allostatic load, and whether the association differs by socioeconomic
      position. METHODS: We recruited a purposive cross-section of midlife (ages 30-50)
      African American women residing in four San Francisco Bay area counties (n =
      208). Racial discrimination was measured using the Experience of Discrimination
      scale. Allostatic load was measured as a composite of 15 biomarkers assessing
      cardiometabolic, neuroendocrine, and inflammatory activity. We calculated four
      composite measures of allostatic load and three system-specific measures of
      biological dysregulation. Multivariable regression was used to examine
      associations, while adjusting for relevant confounders. RESULTS: In the high
      education group, reporting low (b = -1.09, P = .02, 95% CI = -1.99, -0.18) and
      very high (b = -1.88, P = .003, 95% CI = -3.11, -0.65) discrimination was
      associated with lower allostatic load (reference=moderate). Among those with
      lower education, reporting low (b = 2.05, P = .008, 95% CI = 0.55,3.56)
      discrimination was associated with higher allostatic load. Similar but less
      consistent associations were found for poverty status. Associations were similar
      for cardiometabolic functioning, but not for neuroendocrine or inflammatory
      activity. CONCLUSIONS: Racial discrimination may be an important predictor of
      cumulative physiologic dysregulation. Factors associated with educational
      attainment may mitigate this association for African American women and other
      groups experiencing chronic social stress.

PMID- 30286448
TI  - Clinical Features and Prognosis of Nontuberculous Mycobacterial Pleuritis.
AB  - BACKGROUND: While nontuberculous mycobacterial (NTM) pleuritis rarely complicates
      pulmonary NTM infection, high mortality has been reported in case reports and
      small studies. OBJECTIVES: The purpose of this study was to clarify the clinical
      features and treatment outcomes of pulmonary NTM infection cases accompanied by
      NTM pleuritis. METHODS: Medical records of 1,044 patients with pulmonary NTM
      disease were retrospectively reviewed to select patients complicated by NTM
      proven pleuritis. We investigated clinical characteristics, pathogens, pleural
      effusion examinations, radiographic findings, treatments, and clinical course of
      the NTM pleuritis patients. RESULTS: Among 1,044 cases with pulmonary NTM, NTM
      pleuritis occurred in 15 cases (1.4%). The mean age was 69 years with a
      performance status of mostly 2 or better (80.0%), and 6 cases (40.0%) were
      complicated by pneumothorax. Subpleural cavities were radiologically detected in
      11 cases (73.3%), and extrapulmonary air-fluid level was detected in 14 cases
      (93.3%). Eleven patients were treated with combinations of 2-4 antimycobacterial
      drugs, including clarithromycin, and 2 patients were treated with isoniazid,
      rifampicin, and ethambutol. Chest tube drainage was performed in 11 cases, and
      surgical approach was added in 6 cases. The pleural effusion of 2 patients
      treated with only antimycobacterial medications gradually deteriorated. Two
      patients died from NTM pleuritis, and 1 patient died from pneumonitis during a
      mean of 1.8 years of follow-up. CONCLUSIONS: Comorbid NTM pleuritis was difficult
      to treat by medical therapy alone and resulted in a poor prognosis. In addition
      to antimycobacterial agents, chest tube drainage and surgical procedures in the
      early stages should be considered to treat NTM pleuritis.

PMID- 30286449
TI  - Pancreatic Thyrotropin Releasing Hormone and Mechanism of Insulin Secretion.
AB  - Thyrotropin releasing hormone (TRH; pGlu-His-ProNH2) is expressed also in
      pancreatic beta cells where it is colocalized in secretory granules with insulin.
      High perinatal changes of the TRH gene expression and TRH concentrations in rat
      pancreatic islets coincide with the perinatal maturation of the adequate insulin
      secretory responsiveness to glucose and other nutrient secretagogues. TRH
      secretion from pancreatic islets is stimulated by glucose and inhibited by
      insulin. Disruption of the TRH gene in knockout mice results in hyperglycemia
      accompanied by impaired insulin secretory response to glucose. Progress in
      understanding TRH - insulin relations may be substantial for improving knowledge
      of pathophysiological mechanisms included in changes of insulin secretion with
      possible clinical impact. Block of the last step of biosynthesis of alpha
      amidated peptides, including TRH by disulfiram (DS) treatment of adult male rats
      subcutaneously with 200 mg/kg for five days in our experiments resulted in barely
      detectable levels of peptidyl-glycine alpha-amidating monooxygenase (PAM) in
      their pancreatic islets. TRH in physiological concentration (1 nM) does not
      affect basal insulin secretion from intact rat pancreatic islets. In contrast,
      basal insulin secretion from islets of DS-treated rats is four times higher
      compared to controls and could not be further stimulated by high-glucose. The
      addition of 1 nM TRH into medium decreased immediately basal insulin secretion in
      DS (TRH lacking) islets to control level and normalized also their response to
      glucose. Interestingly, absence of the secretory response to glucose in islets
      from TRH depleted rats was connected with their increase of insulin content
      during stimulation. Glucose stimulation together with 1 nM TRH normalized also
      insulin content in DS islets. Apparently, high insulin content in islets from TRH
      depleted animals is a result of block of regulatory secretion pathway redirected
      to constitutional secretion which was corrected by the addition of TRH. Type 2
      diabetes mellitus is a disease characterized by various range from predominant
      insulin resistance with relative insulin deficiency to a predominant secretory
      defect with insulin resistance. These symptoms suggest a possible role of TRH
      dysregulation. In conclusion, presence of TRH in beta cells ensures appropriate
      low basal (constitutive) insulin secretion. Release of TRH induced by glucose and
      possibly by other secretagogues has autocrine effect resulting in directing
      insulin secretion to regulatory pathway reacting to stimulation. If some defects
      of insulin secretion could be treated by TRH, various ways of applications (also
      oral and nasal) could be utilized. Moreover, positive side effects shown in
      animal experiments may accompany the treatment: TRH has the potential to prevent
      apoptosis and promotes insulin-producing cell proliferation and has also aging
      reversing properties.

PMID- 30286451
TI  - Blood Pressure Seasonality in Hemodialysis Patients from Five European Cities of
      Different Latitudes.
AB  - BACKGROUND/AIMS: Climate influences the regulation of blood pressure (BP). Our
      objective was to precisely estimate BP seasonality in hemodialysis (HD) patients
      from five European cities with marked climate differences. METHODS: Stable
      prevalent HD patients from 5 European facilities (Santa Cruz de Tenerife (Spain),
      Seville (Spain), Montpellier (France), Ottignies (Belgium), Umea (Sweden))
      present over the years 1995-1999 were included in this historical longitudinal
      observational study. Individual monthly averages of pre-dialysis BP level were
      computed from all facility BP measurements (> 90 000 observations). The
      association between BP level and location, seasons and meteorological
      measurements was analyzed by mixed models. RESULTS: 261 patients were included
      and followed-up for a median duration of 2 years (6903 monthly observations). Pre
      dialysis SBP and DBP were minimal in summer (July) and maximal in winter
      (November and December), and mean changes were respectively 4.2 [3.0; 5.4] and
      2.0 [1.3; 2.7] mmHg. Seasonality was confirmed in 4 locations (Pseason<=0.001 for
      SBP and DBP), but not in Umea (both Pseason> 0.05). Seasonal changes in DBP were
      larger in southern locations (Pinteraction=0.02). BP level was associated with
      climate parameters: in a positive manner with humidity or rainfall, and inversely
      with sunshine duration or temperature. The effects of temperature and rainfall on
      DBP varied with latitude (Pinteraction< 0.02) and were greater in southern
      locations. CONCLUSION: BP varies with seasons and climate in different European
      areas and seasonality can be more important in southern locations. These changes
      in BP deserve attention as they may be responsible for a significant increase in
      cardiovascular risk which may be preventable.

PMID- 30286450
TI  - Zinc Supplementation Attenuates Cardiac Remodeling After Experimental Myocardial
      Infarction.
AB  - BACKGROUND/AIMS: The objective of our study was to evaluate the effects of zinc
      supplementation on cardiac remodeling following acute myocardial infarction in
      rats. METHODS: Animals were subdivided into 4 groups and observed for 3 months:
      1) Sham Control; 2) Sham Zinc: Sham animals receiving zinc supplementation; 3)
      Infarction Control; 4) Infarction Zinc. After the followup period, we studied
      hypertrophy and ventricular geometry, functional alterations in vivo and in
      vitro, changes related to collagen, oxidative stress, and inflammation, assessed
      by echocardiogram, isolated heart study, western blot, flow cytometer,
      morphometry, and spectrophotometry. RESULTS: Infarction induced a significant
      worsening of the functional variables. On the other hand, zinc attenuated both
      systolic and diastolic cardiac dysfunction induced by infarction. Considering the
      infarct size, there was no difference between the groups. Catalase and superoxide
      dismutase decreased in infarcted animals, and zinc increased its activity. We
      found higher expression of collagens I and III in infarcted animals, but there
      was no effect of zinc supplementation. Likewise, infarcted animals had higher
      levels of IL-10, but without zinc interference. Nrf-2 values were not different
      among the groups. Infarction increased the amount of Treg cells in the spleen as
      well as the amount of total lymphocytes. Zinc increased the amount of CD4+ in
      infarcted animals, but we did not observe effects in relation to Treg cells.
      CONCLUSION: zinc attenuates cardiac remodeling after infarction in rats; this
      effect is associated with modulation of antioxidant enzymes, but without the
      involvement of collagens I and III, Nrf-2, IL-10, and Treg cells.

PMID- 30286452
TI  - Partial 5p Deletion and Partial 5q Duplication in a Patient with Multiple
      Congenital Anomalies: A Two-Step Mechanism in Chromosomal Rearrangement Mediated
      by Non-Allelic Homologous Recombination.
AB  - We describe a 5-month-old female who presented with clinical features of 5p
      deletion syndrome, including high-pitched cry, microcephaly, micrognathia,
      bilateral preauricular tags, bifid uvula, abnormal palmar creases, bilateral
      hypoplastic nipples, feeding difficulties, and developmental delay. In addition,
      the patient also had a cardiac defect, proximal esophageal atresia, and distal
      tracheoesophageal fistula. aCGH of the patient revealed a 22.9-Mb deletion of
      chromosome 5p15.33p14.3 and an 8.28-Mb duplication of chromosome 5q12.1q13.2.
      Parental chromosome analysis indicated that these alterations are de novo.
      Chromosome and FISH analysis demonstrated that the 5q12.1q13.2 duplicated segment
      was attached to the 5p14.3 region with the band 5q12.1 more distal to the
      centromere than the band 5q13.2. Based on the bioinformatic analysis, we
      postulate a mechanism for the formation of this complex rearrangement of
      chromosome 5 by 2-step-wise events mediate by nonallelic homologous recombination
      between low copy repeats. To the best of our knowledge this rearrangement found
      in our patient has not been reported in the literature. This report demonstrates
      the value of chromosome analysis in conjunction with FISH and aCGH for
      identification of complex rearrangements which cannot be revealed by array
      analysis alone.

PMID- 30286453
TI  - A Challenging Prenatal QF-PCR Rapid Aneuploidy Test Result Caused by a Maternally
      Inherited Triplication within Chromosome Xq26.2.
AB  - The aim of this study was to investigate the origin of the biallelic trisomic
      amplification pattern of the X chromosome microsatellite marker DXS1187 in an
      otherwise normal male fetus, identified on routine rapid aneuploidy detection
      (RAD) testing by quantitative fluorescent-polymerase chain reaction (QF-PCR).
      Amniocentesis was performed on a 35-year-old female at 15 weeks, 2 days gestation
      for a positive first trimester screen. QF-PCR, metaphase FISH, and chromosomal
      microarray were carried out on both maternal and fetal DNA. Fetal QF-PCR showed a
      biallelic trisomic pattern for the X chromosome microsatellite marker DXS1187,
      with an otherwise normal male amplification pattern at all other sex chromosome
      markers. Chromosome analysis performed on cultured amniocytes showed a normal
      male karyotype. Chromosome microarray analysis identified a maternally inherited
      304-kb copy number triplication within chromosome Xq26.2 encompassing the DXS1187
      marker. The maternally inherited X chromosome harbors an apparently tandem 304-kb
      triplication that overlaps the DXS1187 marker. As the triplicated region is
      devoid of clinically relevant genes, it was considered as likely benign in the
      fetus. Postnatal follow-up reported a healthy male newborn. To our knowledge,
      this is a unique case demonstrating a "benign" copy number imbalance involving
      the DXS1187 marker detected by prenatal QF-PCR RAD.

PMID- 30286454
TI  - Chronic Fatigue Syndrome: From Chronic Fatigue to More Specific Syndromes.
AB  - In the last decade, a group of chronic disorders associated with fatigue (CDAF)
      emerged as the leading cause of chronic fatigue, chronic pain, and functional
      impairment, all of which have been often labeled in clinical practice as chronic
      fatigue syndrome (CFS) or fibromyalgia. While these chronic disorders arise from
      various pathophysiologic mechanisms, a shared autoimmune or immune-mediated
      etiology could shift the focus from symptomatic treatment of fatigue and pain to
      targeted immunomodulatory and biological therapy. A clinical paradigm shift is
      necessary to reevaluate CFS and fibromyalgia diagnoses and its relationship to
      the CDAF entities, which would ultimately lead to a change in diagnostic and
      therapeutic algorithm for patients with chronic fatigue and chronic pain. Rather
      than uniformly apply the diagnoses of CFS or fibromyalgia to any patient
      presenting with unexplained chronic fatigue or chronic pain, it may be more
      beneficial and therapeutically effective to stratify these patients into more
      specific diagnoses in the CDAF group.

PMID- 30286455
TI  - Megestrol Acetate Induces Declarative Memory Changes and Cortisol Suppression in
      Healthy Volunteers.
AB  - BACKGROUND: The effects of the glucocorticoid and progesterone receptor agonist
      megestrol on declarative memory, and the ability of phenytoin to block these
      effects, were assessed. METHODS: Healthy volunteers received each medication
      combination (placebo and megestrol, phenytoin and megestrol, and placebo and
      placebo) using a randomized, crossover design. The Rey Auditory Verbal Learning
      Test assessed declarative memory. RESULTS: Megestrol was associated with a
      significant reduction in declarative memory (p = 0.0008), which was attenuated by
      phenytoin, and was associated with significant cortisol suppression compared to
      placebo (p < 0.001). CONCLUSION: Changes in memory and cortisol suppression were
      found in healthy volunteers given megestrol.

PMID- 30286456
TI  - Cytologic Features of SMARCA4-Deficient Thoracic Sarcoma: A Case Report and
      Comparison with Other SWI/SNF Complex-Deficient Tumors.
AB  - BACKGROUND: SMARCA4-deficient thoracic sarcoma is a recently proposed entity of
      soft tissue tumors associated with an extremely poor prognosis. Its cytologic
      features have not been well described in the literature yet. CASE: A woman in her
      early 30s who presented with chest pain was found to have a tumor in the right
      chest wall. Cytologic smears revealed numerous atypical round-to-polygonal cells
      appearing singly or in loosely cohesive clusters. These cells had a well-defined
      cell border, scant-to-moderate cytoplasm, and enlarged vesicular nuclei with
      prominent nucleoli. In addition, some cells with eosinophilic globular
      intracytoplasmic inclusions and eccentrically located nuclei, consistent with
      rhabdoid cells, were observed. Immunocytochemically, the cells were at least
      focally positive for cytokeratin CAM5.2 and CD34 and showed a significantly
      reduced BRG1/SMARCA4 expression. The diagnosis was confirmed by histological,
      immunohistochemical, and genetic analysis of a metastatic lesion to the left
      axillary lymph node. CONCLUSION: Although the cytologic features of SMARCA4
      deficient thoracic sarcoma are not fully unique, they are sufficiently
      characteristic to suspect this tumor in cases of supporting clinical and
      radiological features, which may promote additional immunological or molecular
      testing to establish a definitive diagnosis.

PMID- 30286457
TI  - Radial Endobronchial Ultrasound Greyscale Texture Analysis Using Whole-Lesion
      Analysis Can Characterise Benign and Malignant Lesions without Region-of-Interest
      Selection Bias.
AB  - BACKGROUND: Radial-probe endobronchial ultrasound (RP-EBUS) is predominantly used
      clinically for the localisation of peripheral pulmonary lesions prior to biopsy.
      However, the RP-EBUS image itself contains information that can characterise the
      aetiology of lesions. OBJECTIVES: The aim of this study was to show the utility
      of RP-EBUS image analysis using unconstrained regions of interest (ROIs) that
      utilise more image information and eliminate ROI selection bias. METHODS: We
      developed custom software to analyse RP-EBUS images digitally captured during
      clinical procedures. Unconstrained ROIs were mapped onto lesions. We computed
      first-order greyscale image statistics of minimum, maximum, mean, standard
      deviation and range of pixel intensities, and entropy. We also computed second
      order greyscale texture features of contrast, correlation, energy and
      homogeneity. The results of image analysis were compared to gold-standard tissue
      diagnosis. Features from expert- and non-expert-defined ROIs were also compared.
      RESULTS: Eighty-five images were analysed (38 benign and 47 malignant). Five
      greyscale features were significantly different between benign and malignant
      lesions. Benign lesions had higher mean (p < 0.01) and maximal (p < 0.001)
      intensity, greater range (p < 0.001) of pixel intensities and greater entropy (p
      < 0.01). The highest positive predictive values were associated with maximal
      (87.8%) and range of pixel (83.8%) intensities. There were no significant
      differences between expert- and non-expert-defined ROIs. CONCLUSION: RP-EBUS
      image analysis using unconstrained ROIs eliminates ROI selection bias and can
      characterise benign and malignant lesions with an accuracy of up to 85%.

PMID- 30286458
TI  - Energy (Im-)Balance in Frugivorous Lemurs in Southern Madagascar: A Preliminary
      Study in Lemur catta and Eulemur rufifrons * collaris.
AB  - The reproductive cycle of several lemur species is synchronized by photoperiodic
      changes and it is attuned to the seasonal fluctuations in food supply.
      Nevertheless, irregular periods of food shortage occur in Madagascar, which can
      result in a negative energy balance and reduced fitness, especially in
      frugivorous species. Here, we tested whether ring-tailed lemurs (Lemur catta) and
      brown lemurs (Eulemur rufifrons * collaris) use fat stores to maintain their
      energy balance in a gallery forest of Madagascar (Berenty Reserve). We assessed
      the energy intake from weight-based estimates of food intake (mouthful count) and
      macronutrient contents in the diet during dry and wet months. The metabolizable
      energy ingested by these frugivorous/folivorous species was high during the late
      wet season, but it was insufficient to meet their energy requirements during the
      dry season. These preliminary data suggest that these lemurs must store
      sufficient amount of fat mass during the period of food abundance to meet their
      maintenance requirements and to cope with the energetic burden of the mating
      season. Estimates based on models assuming no fiber digestibility during the dry
      season are consistent with the prediction that brown lemurs should supplement
      their daytime diet with nighttime feeding in addition to the use of body fat
      stores.

PMID- 30286459
TI  - Impact of the Choice of IGF-I Assay and Normative Dataset on the Diagnosis and
      Treatment of Growth Hormone Deficiency in Children.
AB  - BACKGROUND: The analysis of insulin-like growth factor I (IGF-I) is an important
      tool for pediatricians in the diagnosis and treatment of growth hormone
      deficiency in children. However, significant differences exist in IGF-I assays
      and normative datasets, which can have important clinical consequences. METHODS:
      IGF-I analyses were performed using the IDS-iSYS platform on 1,897 samples from
      pediatric patients (0.5-18 years old). Z-scores were calculated based on
      normative IGF-I data from Bidlingmaier et al. (SD-BM) [J Clin Endocrinol Metab.
      2014 May; 99(5): 1712-21] and normative IGF-I data from the IGF-I harmonization
      program in the Netherlands (SD-NL). The differences in Z-scores were analyzed at
      relevant clinical decision points (-2 SD, +2 SD). These normative datasets were
      also compared to normative data reported by Elmlinger et al. [Clin Chem Lab Med.
      2004; 42(6): 654-64]. RESULTS: The difference in Z-score between SD-BM and SD-NL
      was highest in males between 0 and 3 years old, exceeding 2 SD. Clinically
      relevant discordance between both Z-scores at -2 and +2 SD was found in 12.7% of
      all samples. The IGF-I levels at -2 and +2 SD reported in the normative dataset
      of Elmlinger et al. were up to 100% higher than the IGF-I levels reported by
      Bidlingmaier et al. or the Dutch harmonization program. CONCLUSION: Pediatricians
      and laboratory specialists should be aware of relevant differences that can exist
      between IGF-I assays and normative data. Well-defined pediatric reference ranges
      for the IDS-iSYS platform are highly desirable.

PMID- 30286461
TI  - Fric Test Revisited: A Suggestion for a New Scoring System and Its Correlation
      with Urticaria Control Test and Dermatology Life Quality Index.
AB  - BACKGROUND: Fric test is a useful tool for the diagnosis and threshold testing
      for symptomatic dermographism. When threshold testing is not available, Urticaria
      Control Test (UCT) and Dermatology Life Quality Index (DLQI) might be used to
      assess disease control and quality of life (QoL) impairment, respectively.
      OBJECTIVES: In this study, we aimed to describe a new scoring system for the Fric
      test and evaluate the correlations of Fric scores with UCT, DLQI, and other
      disease activity assessment scores. METHOD: Provocation test with Fric Test 4.0
      was performed in all patients at referral and at the 4th week. We considered a 4
      grade rating score for Fric Test (0-4) [Total Fric Score (TFS)]. A positive
      response with all of the four pins suggested severe dermographism (TFS = 4),
      while a wheal with only the largest pin (4.5 mm) was considered as milder disease
      (TFS = 1). Treatment responses were evaluated with Fric Test 4.0, UCT, patient's
      global assessment of disease severity (PatGA-VAS), the physician's global
      assessment of disease control (PhyGA-VAS), and DLQI at baseline and at the 4th
      week of treatment. The correlations of TFS with UCT, DLQI, PatGA-VAS, PhyGA-VAS
      at baseline as well as the changes in the mean scores after treatment (week 4)
      were performed. RESULTS: The mean UCT and DLQI scores were 8.69 +/- 3.40 and 7.88
      +/- 6.02 at the first visit. At the second visit, TFS decreased from a mean of
      2.79 +/- 1.68 to 1.91 +/- 1.85 (p < 0.001), and UCT scores and PhyGA-VAS were
      increased (p < 0.001), while DLQI scores, PatGA-VAS, and pruritus scores
      decreased significantly (p = 0.002; p = 0.001; p = 0.012). There was a positive
      correlation between TFS and pruritus scores (r = 0.378) and DLQI scores (r =
      0.392). TFS was found to have a negative correlation with UCT score (r = -0.283)
      and PhyGA-VAS (r = -0.347). CONCLUSIONS: This new Fric scoring system allows
      comparison with other tools and shows moderate correlations with most of the
      tools. Using disease-specific tools is recommended since they provide a
      subjective evaluation of disease severity, QoL impairment, and disease control.

PMID- 30286463
TI  - Is Peritoneal Dialysis a Suitable Renal Replacement Therapy Option for Polycystic
      Kidney Disease Patients?
AB  - BACKGROUND/AIMS: Mounting clinical experience and evidence from scale
      observational studies have suggested that polycystic kidney disease (PKD) was not
      a contraindication for peritoneal dialysis (PD). Recent studies have reported
      that PD may be associated with a better prognosis in PKD than that of non-PKD
      patients. To solve the problem, we performed a systematic review and
      comprehensive meta-analysis to compare the outcomes between PKD and non-PKD
      patients on PD and the all-cause mortality between patients with PKD on PD and
      hemodialysis (HD). METHODS: We conducted a systematic literature using electronic
      databases (PubMed, Ovid, Embase and Web of Science) to identify the studies
      reporting the endpoint events of PKD/non-PKD patients with PD and the all-cause
      mortality between patients with PKD on PD and HD, such as dialysis adequacy,
      technique failure, PD-related complications, the mode of RRT change, and all
      cause mortality. We searched the literature published February 2018 or earlier.
      We used both fix-effects and random-effects models to calculate the overall
      effect estimate. A sensitivity analysis and subgroup analysis were performed to
      find the origin of heterogeneity. RESULTS: 12 studies with a total of 17,040
      patients reported the endpoint events of PKD/non-PKD patients with PD. No
      significant difference was observed on dialysis adequacy (Kt/V, SMD: -0.02,
      95%CI: -0.12-0.08; D: Pcr (4h), SMD: -0.10, 95% CI: -0.26-0.06), technique
      failure (RR: 0.97, 95%CI: 0.78-1.20), RRT change (RR: 0.96, 95%CI: 0.77-1.19),
      total PD-associated complications (RR: 1.0, 95%CI: 0.91-1.09) and all-cause
      mortality (RR: 0.40, 95%CI: 0.33-0.47) in PKD patients, compared with non-PKD
      subjects undergoing PD. However, the proportion of renal transplantation in PKD
      patients was higher than that of non-PKD patients (RR: 2.04, 95%CI: 1.88-2.20)
      with significant heterogeneity (I2 =82.7%, P=0.000). 4 studies with a total of
      5,762 patients reported that the all-cause mortality did not differ between the
      PKD patients on PD and HD (RR: 0.87, 95%CI: 0.72-1.06). CONCLUSION: Our meta
      analysis found that the outcomes of given population of PKD patients on PD were
      at least not inferior as compared to those with other primary kidney diseases,
      and suggested that PKD might be not absolutely a contraindication for PD. Given
      the limitations of the proposed, it needs further large-scale studies to assess
      whether PD is a suitable RRT option for end-stage renal disease (ESRD) patients
      with PKD.

PMID- 30286464
TI  - New European Organization for Clinical Psychology and Psychological Treatments:
      EACLIPT.

PMID- 30286462
TI  - Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function.
AB  - BACKGROUND/AIMS: Age-related cataract (ARC) remains the leading cause of visual
      impairment among the elderly population. Long non-coding RNAs (lncRNAs) have
      emerged as potential regulators in many ocular diseases. However, the role of
      lncRNAs in nuclear ARC, a subtype of ARC, requires further elucidation. METHODS:
      LncRNA sequencing was performed to identify differentially expressed lncRNAs
      between the capsules of transparent and nuclear ARC lenses. Expression validation
      was confirmed by qRT-PCR. MTT assay, Calcein-AM and propidium iodide double
      staining, Rhodamine 123 and Hoechst double staining, EdU and transwell assay were
      used to determine the role of H19 or miR-675 in the viability, apoptosis,
      proliferation and migration of primary cultured human lens epithelial cells
      (HLECs). Bioinformatics and luciferase reporter assays were used to identify the
      binding target of miR-675. RESULTS: Sixty-three lncRNAs are differentially
      expressed between the capsules of transparent and nuclear ARC lenses. One top
      abundantly expressed lncRNA, H19, is significantly up-regulated in the nuclear
      ARC lens capsules and positively associated with nuclear ARC grade. H19 knockdown
      accelerates apoptosis development and reduces the proliferation and migration of
      HLECs upon oxidative stress. H19 is the precursor of miR-675, and a reduction of
      H19 inhibits miR-675 expression. miR-675 regulates CRYAA expression by targeting
      the binding site within the 3'UTR. Moreover, miR-675 increases the proliferation
      and migration while decreasing the apoptosis of HLECs upon oxidative stress.
      CONCLUSION: H19 regulates HLECs function through miR-675-mediated CRYAA
      expression. This finding would provide a novel insight into the pathogenesis of
      nuclear ARC.

PMID- 30286465
TI  - Exposure to Environmental Tobacco Smoke and Prevalence of Atopic Dermatitis among
      Adolescents in Kuwait.
AB  - BACKGROUND: This study aimed to (i) assess the prevalence of exposure to
      environmental tobacco smoke (ETS) at homes, (ii) assess the prevalence of atopic
      dermatitis and (iii) evaluate the association between ETS exposure and atopic
      dermatitis status among adolescents. METHODS: During October 2015, a cross
      sectional study design was implemented using a self-administered, modified
      version of the ISAAC (International Study of Asthma and Allergies in Childhood)
      questionnaire among students enrolled in nine high schools of one of the six
      governorates of Kuwait. Prevalence of ETS exposure at home (1 or more smokers at
      home vs. none) and atopic dermatitis were computed. A multivariable log-binomial
      regression model was used to evaluate the adjusted association between ETS
      exposure and atopic dermatitis. RESULTS: Of 800 invited students, 746 (93.3%)
      participated, of whom 74.8% were Kuwaiti and 50.1% were female with a mean (SD)
      age of 16.8 (0.68) years. Prevalence of ETS exposure at home was 54%. Prevalence
      of atopic dermatitis was 14.9%. A final multivariable log-binomial regression
      model showed that compared with the adolescents free from atopic dermatitis,
      adolescents with atopic dermatitis were significantly more likely to have had ETS
      exposure at home (adjusted prevalence ratio = 1.49; 95% CI: 1.03-2.14; p = 0.034)
      or tended to be female (adjusted prevalence ratio = 1.42; 95% CI: 0.99-2.03; p =
      0.054). CONCLUSIONS: A high prevalence of ETS exposure at home among adolescents
      was recorded. ETS exposure and female gender were significantly associated with
      atopic dermatitis status. Intervention fostering voluntary adoption of a smoke
      free home rule may help protect the adolescents against ETS exposure and
      alleviate the menace of associated morbidity.

PMID- 30286466
TI  - Utility of Regular Management of Physical Activity and Physical Function in
      Hemodialysis Patients.
AB  - BACKGROUND/AIMS: Several clinical practice guidelines recommend regular
      assessment of physical activity and physical function as part of routine care in
      hemodialysis patients. However, there is no clear evidence to support these
      recommendations. We investigated whether the proportion of attendance at a
      regular program for management of physical activity and physical function can
      predict all-cause mortality and cardiovascular events in hemodialysis patients.
      METHODS: This retrospective cohort study consisted of 266 hemodialysis patients
      participating in the management program at least once. Participants were tracked
      for 3 years after their first attendance at the management program to determine
      their attendance proportion. The main study outcomes included all-cause mortality
      and a composite of fatal and nonfatal cardiovascular events. RESULTS: Median
      patient age was 64.5 (interquartile range, 56.8 - 72.0) years, 45% were women,
      and the median time on hemodialysis was 35.5 (interquartile range, 12.0 - 114.3)
      months at baseline. Sixty-five patients died over a median follow-up of 79
      months. The incidence of cardiovascular events was 60 over a median follow-up of
      68 months. Even after adjusting for any of the prognostic models, participants
      who attended <= 75% of sessions (n = 140) had higher risks of mortality (hazard
      ratio (HR), 1.79; 95% confidence interval (CI): 1.00 - 3.36; P = 0.049) and
      cardiovascular events (HR, 1.84; 95% CI: 1.07 - 3.48; P = 0.03) than those
      attending > 75% of sessions (n = 126). CONCLUSION: Hemodialysis patients in whom
      physical activity and physical function could be assessed more regularly had
      better prognosis than those with only intermittent assessment.

PMID- 30286468
TI  - Is Early Complement Activation in Renal Transplantation Associated with Later
      Graft Outcome?
AB  - BACKGROUND/AIMS: Complement activation is important in post-transplantation renal
      injury, but data on its role as predictor of transplant outcome/complications
      when assessed in donor kidneys are lacking. METHODS: In human renal transplant
      biopsies with delayed graft function (DGF, n=12), antibody mediated rejection
      (ABMR, n=8), T-cell mediated rejection (TCMR, n=11), 1 year protocol biopsies
      (control, n=10) and corresponding zero-biopsies we performed immunohistochemical
      analyses of 6 complement factors using FFPE sections and correlated the findings
      with kidney function, as assessed by serum creatinine, and morphological changes
      including interstitial fibrosis and tubular atrophy (IF/TA). RESULTS: In DGF,
      TCMR and ABMR significant complement deposition was observed, which was less
      pronounced in corresponding zero-biopsies. Zero-biopsies with subsequent ABMR
      showed glomerular complement factor D and C3c expression. Moreover, glomerular
      C3c and C9 and tubular MASP-2 and Collectin-11 expression in zero-biopsies
      significantly correlated with serum creatinine at diagnosis of DGF, TCMR or ABMR.
      Glomerular C1q was significantly increased in ABMR, but not in DGF and TCMR. In
      contrast, peritubular C1q was significantly enhanced in DGF and TCMR compared to
      zero-biopsies. Using C3d as a surrogate marker for complement activity we could
      confirm that stained complement factors are frequently associated with complement
      activity. CONCLUSION: Complement deposition strongly correlated with
      histopathological changes observed in renal transplants. All 3 complement
      pathways were operational in biopsies with DGF, TCMR and ABMR albeit with
      differential abundance and localization. Since complement deposition in zero
      biopsies correlated with graft function and morphological changes, early specific
      complement inhibition in renal transplantation may be a new therapeutic option to
      prevent graft loss.

PMID- 30286467
TI  - Omi/HtrA2 Regulates a Mitochondria-Dependent Apoptotic Pathway in a Murine Model
      of Septic Encephalopathy.
AB  - BACKGROUND/AIMS: the pathogenesis of sepsis-associated encephalopathy (SAE) is
      multifactorial, involving neurotransmitter alterations, inflammatory cytokines,
      oxidative damage, mitochondrial dysfunction, apoptosis, and other factors.
      Mitochondria are major producers of reactive oxygen species, resulting in
      cellular injury. Omi/HtrA2 is a proapoptotic mitochondrial serine protease
      involved in caspase-dependent cell death; it is translocated from mitochondria to
      the cytosol after an apoptotic insult. We previously found that UCF-101, a
      specific inhibitor of Omi/HtrA2, has neuroprotective effects on cerebral
      oxidative injury and cognitive impairment in septic rats. In this study, the
      mechanisms and molecular pathways underlying these effects were investigated.
      METHODS: Male Sprague-Dawley rats were subjected to cecal ligation and puncture
      (CLP) or sham-operated laparotomy and were administered vehicle or UCF-101 (10
      umol/kg). The hippocampus was isolated for subsequent analysis. Omi/HtrA2
      expression in the mitochondria or cytosol was evaluated by immunofluorescence or
      western blotting. Terminal deoxynucleotidyl transferase dUTP nick end labeling
      staining was utilized to evaluate levels of apoptosis, and western blotting was
      used to evaluate apoptosis-related proteins, such as cleaved caspase-3, caspase
      9, and poly (ADP-ribose) polymerase (PARP). Tight junction expression was
      assessed by immunofluorescence and western blotting. Mitochondrial function,
      inflammatory cytokines, and oxidative stress were also assayed. In addition, a
      wet/dry method was used to evaluate brain edema and Evans blue extravasation was
      used to evaluate blood-brain barrier (BBB) integrity. RESULTS: After CLP
      treatment, the hippocampus exhibited a mild increase in Omi/HtrA2 expression;
      cytosolic Omi/HtrA2 expression increased significantly, whereas mitochondrial
      Omi/HtrA2 expression was reduced, indicating that CLP-induced oxidative stress
      resulted in the translocation of Omi/HtrA2 from mitochondria to the cytosol.
      Hippocampal cleaved caspase-3, caspase-9, and PARP levels were significantly
      higher in animals treated with CLP than in sham-operated animals, while XIAP
      expression was lower. Treatment with UCF-101 prevented the mobilization of
      Omi/HtrA2 from mitochondria to the cytosol, attenuated XIAP degradation, and
      decreased cleaved caspase-3, caspase-9, and PARP expression as well as apoptosis.
      UCF-101 also reversed the decreased mitochondrial complex I, II, and III
      respiration and the reduced ATP caused by CLP. In addition, UCF-101 treatment
      resulted in a significant improvement in BBB integrity, as demonstrated by
      increased occludin, claudin-5, and zonula occludens 1 levels and reduced Evans
      blue extravasation. No significant effects of UCF-101 on brain edema were found.
      Inflammatory cytokines and oxidative stress were significantly higher in the CLP
      treated group than in the sham-operated group. However, the inhibition of
      Omi/HtrA2 by UCF-101 significantly alleviated these responses. CONCLUSION: Our
      data indicated that Omi/ HtrA2 regulates a mitochondria-dependent apoptotic
      pathway in a murine model of septic encephalopathy. Inhibition of Omi/HtrA2 by
      UCF-101 leads to neuroprotection by inhibiting the cytosolic translocation of
      Omi/HtrA2 and antagonizing the caspase-dependent apoptosis pathway. Therapeutic
      interventions that inhibit Omi/HtrA2 translocation or protease activity may
      provide a novel method to treat SAE.

PMID- 30286470
TI  - Editorial Board / Contents / Imprint.

PMID- 30286469
TI  - MicroRNA-29a Inhibits Growth, Migration and Invasion of Melanoma A375 Cells in
      Vitro by Directly Targeting BMI1.
AB  - BACKGROUND/AIMS: Melanoma is one of the most aggressive malignant tumors, with
      increasing incidence, poor prognosis, and lack of any effective targeted
      therapies. Abnormal expression of miR-29a has been found in several types of
      cancers, including melanoma. In this study, experiments were performed to
      investigate the role of miR-29a in melanoma, and the molecular mechanism by which
      miR-29a represses melanoma. METHODS: miR-29 and Bmi1 expression was examined by
      quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability,
      apoptosis, migration and invasion were respectively determined by Cell Counting
      Kit-8 assay, Propidium iodide (PI) fluorescein isothiocynate (FITC)-Annexin V
      staining assay, wound healing assay and transwell assay. Luciferase reporter
      assay was performed to determine a target gene of miR-29a. Western blot was used
      to analyze protein expression of apoptosis-related proteins, Bmi1, Wnt/beta
      catenin and Nuclear factor-kappaB (NF-kappaB) pathway target genes. RESULTS: miR
      29a was down-regulated in all tested melanoma cell lines. Up-regulation of miR
      29a effectively inhibited cell viability, migration, and invasion, but promoted
      apoptosis in A375 cells. Bmi1 was a direct target gene of miR-29a. Transfection
      with miR-29a mimic decreased cell migration and invasion and Bmi1 expression in
      Malme-3M cells, SK-MEL-2, SK-MEL-5, and M14 cell lines. Moreover, miR-29a might
      suppress growth, migration and invasion of A375 cells by negatively regulating
      Bmi1. In addition, our results demonstrated that transfection with miR-29a mimic
      effectively blocked Wnt/beta-catenin and NF-kappaB pathways via down-regulating
      Bmi1. CONCLUSION: miR-29a could be functioned as a potential tumor suppressor
      through direct regulation of Bmi1 in melanoma cells.

PMID- 30286471
TI  - 'Diseases Desperate Grown by Desperate Appliance Are Relieved, or Not at all' -
      Towards Finding a Cure for Pancreatic Cancer, Where Do We Stand Today?

PMID- 30286472
TI  - Current Therapeutic Options for Pancreatic Ductal Adenocarcinoma.
AB  - Pancreatic cancer remains the fourth most common cause of cancer-related
      mortality and is a major health threat. The majority of cases are diagnosed at
      advanced disease stages, limiting the chances of long-term survival. Several new
      therapeutic regimens have been introduced into routine clinical practice in
      recent years and a plethora of novel approaches is currently undergoing
      preclinical and early clinical evaluation. This review discusses the current
      standards of care for systemic therapy of pancreatic cancer and gives a brief
      outlook on ongoing clinical trials.

PMID- 30286474
TI  - Erratum.

PMID- 30286473
TI  - Targeting Defects in the Cellular DNA Damage Response for the Treatment of
      Pancreatic Ductal Adenocarcinoma.
AB  - Pancreatic cancer is one of the most common causes of cancer-related mortality in
      the Western world and pancreatic ductal adenocarcinoma (PDAC) is by far the most
      common pancreatic cancer entity. Locally advanced or metastatic PDAC remains a
      major clinical challenge, and the prognosis of affected patients is dismal
      despite substantial research efforts in this area. Recent large-scale genomic
      analyses of PDAC revealed that KRAS is the most frequently mutated driver gene in
      this entity. In addition, a relatively large proportion of PDAC patients displays
      germline variants in genes involved in DNA repair, particularly DNA double-strand
      repair. Similarly, a sizable fraction of sporadic PDAC cases harbor mutations in
      genome maintenance genes, such as BRCA1, BRCA2, and ATM. While direct targeting
      of oncogenic KRAS is currently not possible in the clinical setting, these
      defects in DNA repair may open new therapeutic avenues. Here, we discuss the
      potential use of compounds that interfere with DNA repair and genome maintenance
      mechanisms for the treatment of PDAC. We particularly focus on the genotype
      tailored use of compounds, such as PARP inhibitors, as well as ATR- and DNA
      protein kinase catalytic subunit (PKcs) inhibitors.

PMID- 30286475
TI  - PharmaNews.

PMID- 30286476
TI  - PharmaNews.

PMID- 30286477
TI  - Meetings and Conferences.

PMID- 30286479
TI  - Use of Self-Medication with Homeopathy in Germany: Results of an Online
      Questionnaire Survey.

PMID- 30286478
TI  - Cell-Free DNA and Neuromediators in Detecting Aggressive Variant Prostate Cancer.
AB  - BACKGROUND: Aggressive variant transformation in metastatic castration-resistant
      prostate cancer (mCRPC) represents an under-recognized phenomenon. There is an
      urgent need for non-invasive biomarkers to detect these variants and identify
      treatment alternatives. METHODS: A prospective observational pilot study in mCRPC
      patients receiving treatment with cabazitaxel (CAB) was conducted. Neuromediators
      were sequentially evaluated and their impact on disease endpoints calculated.
      Targeted next-generation sequencing (NGS) of cell-free DNA (cfDNA) was also
      performed in a highly pretreated subset of patients. RESULTS: 23 patients were
      included. Estimated effects indicate that neuron-specific enolase (NSE) levels at
      baseline may be correlated with overall survival (NSE unit 18.3 ng/ml: HR1.262
      (95% confidence interval (CI) 0.985-1.616)) and that chromogranin A (CGA) may be
      correlated with progression-free survival (CGA unit 98.1 ng/ml: HR1.341 (95% CI
      1.011-1.778)). cfDNA analysis revealed mutations annotated in prostate cancer
      (PCA) and small cell cancers (SCC). 1 patient showed elevated neuromediators
      along with annotated mutations in PCA and SCC, potentially indicating aggressive
      variant cancer. In 3 patients KIT mutations (e.g. pM541L, pV654A) known to be
      tissue-based biomarkers with level 1 evidence for the treatment with imatinib and
      sunitinib were found. CONCLUSIONS: Sequential analysis of neuromediators and
      targeted NGS of cfDNA provide insight for the estimation of tumor heterogeneity
      under therapy with CAB.

PMID- 30286480
TI  - Population Genetic Structure of an Endangered Endemic Primate (Leontopithecus
      chrysomelas) in a Highly Fragmented Atlantic Coastal Rain Forest.
AB  - This study evaluated the genetic structure of wild populations of the endangered
      primate, Leontopithecus chrysomelas. We tested the assumption that populations of
      L. chrysomelas, given their larger population size and a higher degree of habitat
      continuity, would have higher genetic diversity and less genetic structuring than
      other lion tamarins. We used 11 microsatellites and 122 hair samples from
      different locations to assess their genetic diversity and genetic structure, and
      to make inferences about the isolation by distance. The overall expected
      heterozygosity (0.51 +/- 0.03) and the average number of alleles (3.6 +/- 0.2)
      were relatively low, as is the case in other endangered lion tamarins. Genetic
      clustering analyses indicated two main clusters, whereas the statistical analyses
      based on genotype similarities and Fst suggested further substructure. A Mantel
      test showed that only 34% of this genetic differentiation was explained by the
      linear distance. In addition to linear distance, structural differences in the
      landscape, physical barriers and behavioural factors may be causing significant
      genetic structuring. Overall, this study suggests that these populations have a
      relatively low genetic diversity and a relatively high population genetic
      structure, putting in question whether the presence of agroforest systems (known
      locally as cabruca) is enough to fully re-establish functional landscape
      connectivity.

PMID- 30286483
TI  - The Effect of Magnesium and Vitamin E Co-Supplementation on Glycemic Control and
      Markers of Cardio-Metabolic Risk in Women with Polycystic Ovary Syndrome: A
      Randomized, Double-Blind, Placebo-Controlled Trial.
AB  - Data on the effects of magnesium and vitamin E co-supplementation on glycemic
      control and markers of cardio-metabolic risk of patients with polycystic ovary
      syndrome (PCOS) were collected. This investigation was conducted to evaluate the
      effects of magnesium and vitamin E co-supplementation on glycemic control and
      markers of cardio-metabolic risk in women with PCOS. This randomized, double
      blind, placebo-controlled trial was carried out on 60 women with PCOS, aged 18-40
      years old. Participants were randomly divided into two groups to receive 250
      mg/day magnesium plus 400 mg/day vitamin E supplements or placebo (n=30 each
      group) for 12 weeks. Fasting blood samples were taken at baseline and after the
      12-week intervention to quantify related variables. After the 12-week
      intervention, compared with the placebo, magnesium and vitamin E co
      supplementation led to a significant reduction in serum insulin levels (-1.1+/
      3.0 vs. +1.6+/-3.7 MUIU/ml, p=0.003) and homeostatic model of assessment for
      insulin resistance (-0.2+/-0.7 vs. +0.4+/-0.9, p=0.002), and a significant
      increase in the quantitative insulin sensitivity check index (+0.01+/-0.01 vs. 
      0.009+/-0.02, p=0.003). Furthermore, magnesium plus vitamin E supplementation
      significantly decreased serum triglycerides (-15.0+/-24.4 vs. +6.7+/-22.2 mg/dl,
      p=0.001) and VLDL-cholesterol concentrations (-3.0+/-4.9 vs. +0.6+/-2.4 mg/dl,
      P=0.01) compared with the placebo. A trend toward a greater decrease in total
      cholesterol levels was observed in magnesium plus vitamin E group compared to
      placebo group (-7.0+/-32.6 vs. +8.1+/-26.6 mg/dl, p=0.05). In conclusion,
      magnesium and vitamin E co-supplementation for 12 weeks to PCOS women had
      beneficial effects on parameters of insulin metabolism and few markers of cardio
      metabolic risk.

PMID- 30286482
TI  - Ghrelin Levels in Basal Conditions and During Glucose Tolerance Test in
      Prediabetic and Diabetic Patients.
AB  - Ghrelin is associated with glucose homeostasis but its' possible relevance with
      glucose levels in physiological and pathological conditions has so far been
      poorly investigated. The aim of the present study was to evaluate circulating
      ghrelin levels in prediabetic and diabetic patients in basal conditions and in
      response to oral glucose tolerance test (OGTT). A total of 90 male adults aged 40
      - 73 years old were enrolled in our study. Fasting and postprandial plasma
      ghrelin, insulin and glucose levels were measured at 0, 60, 120 and 180 min
      following an OGTT in 40 patients with type 2 diabetes mellitus (T2DM), 20 with
      impaired glucose tolerance (IGT) and 30 controls. Incremental and total area
      under response curve were determined and calculated for glucose, insulin and
      ghrelin. Fasting plasma ghrelin concentrations were significantly lower in the
      T2DM group than IGT and control group patients (p<0.01) but not between healthy
      subjects and IGT group (p=0.746). In the diabetics' group ghrelin levels showed a
      statistically significant negative correlation with insulin and a positive
      correlation with HbA1c and glucose. At all time points after the OGTT ghrelin
      concentrations were significantly lower in the T2DM group compared to IGT group
      and controls. Plasma ghrelin concentrations are lower in male diabetic patients
      at the fasting state and remain lower at all time points after an OGTT while
      minor differences were found between normal and IGT subjects. Ghrelin might play
      a role in insulin and glucose metabolism in diabetic patients but not in patients
      with IGT.

PMID- 30286481
TI  - Tectonic Proteins Are Important Players in Non-Motile Ciliopathies.
AB  - Primary cilium is a ubiquitous, tiny organelle on the apex of the mammalian
      cells. Non-motile (primary) ciliopathies are diseases caused by the dysfunction
      of the primary cilium and they are characterized by diverse clinical and genetic
      heterogeneity. To date, nearly 200 genes have been shown to be associated with
      primary ciliopathies. Among them, tectonic genes are the important causative
      genes of ciliopathies. Tectonic proteins including TCTN1, TCTN2, and TCTN3 are
      important component proteins residing at the transition zone of cilia. Indeed,
      many ciliopathies have been reported to involve tectonics mutations, highlighting
      a pivotal role for tectonic proteins in ciliary functions. However, the specific
      functions of tectonic proteins remain largely enigmatic. Herein, we discuss the
      recent advances on the localization and structure of tectonic proteins and the
      functions of tectonic proteins. The increasing line of evidences demonstrates
      that tectonic proteins are required for ciliogenesis and regulate ciliary
      membrane composition. More importantly, Tectonic proteins play a vital role in
      the regulation of the Sonic Hedgehog (Shh) pathway; Tectonic deficient mice show
      the Shh pathway-related developmental defects. Tectonic proteins share similar
      functions including neural patterning and Gli3 processing but also each has a
      unique and indispensable role in the ciliogenesis and signaling pathways. At the
      same time, the mutations of tectonic genes are the causes of a serial of primary
      ciliopathies including Meckel-Gruber syndrome, Oral-facial-digital syndrome, and
      Joubert syndrome. Therefore, full understanding of functions of tectonic proteins
      will help to crack ciliopathies and improve life quality of patients by future
      gene therapy.

PMID- 30286484
TI  - Plasma Irisin Levels in Subjects with Type 1 Diabetes: Comparison with Healthy
      Controls.
AB  - Irisin is a myokine that increases energy expenditure. In this cross-sectional
      study, we examined for differences in plasma irisin concentrations between
      subjects with type 1 diabetes mellitus and healthy individuals and searched for
      associations between plasma irisin levels and clinical and biochemical
      characteristics as well as self-reported physical activity. A total of 79
      subjects with type 1 diabetes [age 38.2+/-12.5 years, men/women (n): 27/52], were
      consecutively recruited. Moreover, 53 healthy controls, matched for age and body
      mass index with those with diabetes were recruited. Plasma irisin was measured
      with ELISA. Participants were asked about their physical activity during the last
      week. We also measured trunk and visceral fat. Circulating irisin levels were
      lower in subjects with diabetes than in controls [median value (interquartile
      range): 53.0 (35.2, 106.3) vs. 178.1 (42.6, 641.6) ng/ml, respectively, p<0.001].
      In the group of diabetes, univariate analysis showed that irisin levels were
      associated with waist circumference (beta=-0.283, p=0.023), serum triglycerides
      (beta=-0.282, p=0.031), and trunk fat (beta=-0.324, p=0.012). In multivariate
      analysis after adjustment for potential confounders, irisin levels were
      associated independently only with waist circumference (beta=-0.403, p=0.005).
      Among controls, multivariate analysis demonstrated that irisin levels were
      associated with pack-years of smoking (beta=-0.563, p=0.012) and fasting
      triglycerides (beta=-0.338, p=0.041). Circulating irisin levels were lower in
      subjects with diabetes in comparison with healthy-matched controls. In
      conclusion, plasma irisin concentrations in subjects with diabetes were
      associated with waist circumference, while in controls with serum triglycerides
      and pack-years of smoking.

PMID- 30286485
TI  - Thyrotropin Receptor Blocking Antibodies.
AB  - Autoantibodies (Ab) against the thyroid-stimulating hormone receptor (TSHR) are
      frequently found in autoimmune thyroid disease (AITD). Autoantibodies to the TSHR
      (anti-TSHR-Ab) may mimic or block the action of TSH or be functionally neutral.
      Measurement of anti-TSHR-Ab can be done either via competitive-binding
      immunoassays or with functional cell-based bioassays. Antibody-binding assays do
      not assess anti-TSHR-Ab functionality, but rather measure the concentration of
      total anti-TSHR binding activity. In contrast, functional cell-based bioassays
      indicate whether anti-TSHR-Ab have stimulatory or blocking activity. Historically
      bioassays for anti-TSHR-Ab were research tools and were used to study the
      pathophysiology of Graves' disease and Hashimoto's thyroiditis. In the past,
      bioassays for anti-TSHR-Abs were laborious and time-consuming and varied widely
      in performance from laboratory to laboratory. Recent advances in the development
      of cell-based assays, including the application of molecular engineering, have
      led to significant improvements that have enabled bioassays to be employed
      routinely in clinical laboratories. The prevalence and functional significance of
      TSHR blocking autoantibodies (TBAb) in autoimmune hypothyroidism has been less
      well investigated compared to TSHR stimulating Ab. There is an increasing body of
      data, however, that demonstrate the clinical utility and relevance of TBAb, and
      thus the importance of TBAb bioassays, in the diagnosis and management of
      patients with AITD. In the present review, we summarize the different methods
      used to measure TBAb, and discuss their prevalence and clinical relevance.

PMID- 30286486
TI  - Current and Future Treatments for Graves' Disease and Graves' Ophthalmopathy.
AB  - The course and pathogenesis of Graves' disease and Graves' ophthalmopathy are
      interdependent, influencing each other's therapeutic choices. Multiple factors
      including geographic location, access to medical services, patient and physician
      preferences influence the management of these conditions. Graves' disease is
      classically managed with one of three treatment options - antithyroid drugs,
      radioactive iodine, and thyroidectomy. In recent years, there has been a shift
      towards antithyroid drugs, including long term therapy with these agents, given
      the advantage of avoiding hypothyroidism and the apparent safety of this
      approach. In addition, new therapies are (slowly) emerging, focusing on
      immunomodulation. Technological advances are opening doors to non-pharmaceutical
      interventions that aim to deal with both structural thyroid abnormalities as well
      as biochemical abnormalities of hyperthyroidism. Graves' ophthalmopathy
      management is guided by its activity and severity status, with treatment options
      including smoking cessation, control of hyperthyroidism, local eye measures,
      glucocorticoids, selenium, orbital radiotherapy, and surgery. In addition to
      these established treatment choices, new immunotherapy-based approaches are being
      tested. Some of them (tocilizumab and teprotumumab) are very promising but
      further evaluation is needed before we can establish their role in clinical care.
      Agents identified as beneficial in Graves' disease management will likely be
      tested in Graves' ophthalmopathy as well. In the coming years, our main clinical
      responsibility will be to find the proper balance between the benefits and
      potential risks of these incoming therapies, and to identify the subgroups of
      patients where this ratio is most likely to favor a safe and successful
      therapeutic outcome.

PMID- 30286487
TI  - [Do We Need a Specialist Physician for Digital Medicine?]

PMID- 30286488
TI  - [Chronic Mesenteric Ischemia].
AB  - Chronic mesenteric ischemia (CMI) is defined by stenoses or occlusions of the
      celiac artery, superior or inferior mesenteric artery. While it is mostly cause
      by atherosclerotic disease, less frequent cause in particular in younger patients
      are fibrowmuscular dysplasia or vasculitis. Risk factors include smoking,
      hypertension, dyslipidemia, higher age, and female sex. Symptomatic CMI only
      accounts for less than 5 % of intestinal ischemic events. The prevalence of
      asymptomatic CMI is unknown but may be as high as 15 % and is more frequent in
      peripheral artery disease (27 %) and abdominal aortic aneurysm (40 %). The celiac
      artery is mostly affected. Abdominal pain that is aggravated with food intake
      with preserved appetite, abdominal bruits, and severe malnutrition can be
      important clinical hints that raise the suspicion of CMI. The diagnostic modality
      of choice is duplex ultrasound that should be performed in specialized centers
      potentially together with functional test causally linking symptoms to relevant
      arterial stenosis or intestinal ischemia. Typically, a stenosis of only one
      artery is unlikely to cause CMI. The therapy of choice is revascularization. In
      most cases angioplasty potentially together with stenting is performed due to low
      post-interventional mortality in mostly multi-morbid patients with excellent
      technical and clinical success rates. Non-atherosclerotic CMI in particular in
      younger patients may require surgery. Similar to the treatment of patients with
      other cardiovascular diseases, atherosclerosis of mesenteric arteries requires
      life style modification and optimal medical therapy for risk reduction. Platelet
      inhibition is indicated after revascularization.

PMID- 30286489
TI  - [Hyperlipidemia: What role do PCSK9 inhibitors play?]
AB  - PCSK9 inhibitors are a new and safe option of lowering LDL cholesterol. This
      article summarizes current recommendations for the use of PCSK9 inhibitors.
      Statins and ezetimibe are still the basis of cholesterol-lowering therapy.
      Through their use, the largest proportion of patients can be adequately treated.
      PCSK9 inhibitors should be used in patients at very high cardiovascular risk if,
      despite the maximum tolerated statin/ezetimibe therapy, an LDL-C reduction of
      more than 50 % would be needed to achieve the recommended LDL-C target. The use
      in patients with familial hypercholesterolemia is usually carried out according
      to this scheme as well. For statin intolerance, PCSK9 inhibitors should be
      considered in patients at very high cardiovascular risk who have not tolerated
      low doses of at least two different statins/ezetimibe.

PMID- 30286490
TI  - [Nutrition at the End of Life - Ethical Aspects].
AB  - Nutritional problems at the end of life are of multifactorial origin, they
      require an interdisciplinary and multiprofessional approach. A basic precondition
      in deciding a nutritional therapeutic intervention is a valid medical indication.
      Fundamental ethical principles have to be respected.Another relevant question is
      if the nutritional therapeutic intervention will serve a meaningful, attainable
      goal in accordance with the patient's individual preferences and whether the
      expected benefit outweighs the potential risks. Particularly in older patients
      with a higher risk of cognitive impairment there is the question of the patient's
      ability to communicate his/her personal preferences, if he/she is able to give
      informed consent.Nutritional problems, particularly the refusal to eat can
      present a burdensome situation for the patient's carers. The potential reasons
      and causes for these problems have to be evaluated by an interdisciplinary
      assessment and medical differential diagnosis. This process has to involve the
      patient, his family and carers, ethical and palliative care counsel should be
      available.The topic of artificial feeding by means of a percutaneous gastrostomy 
      its relevance in the end of life situation, particularly in advanced stages of
      dementia is also addressed.

PMID- 30286491
TI  - [Medical Treatment of Soft Tissue Sarcoma].
AB  - Soft tissue sarcomas are a diagnostically and therapeutically complex disease.
      This is due to the pronounced heterogeneity, characterized by biologically very
      different histological subtypes and the resulting clinical progressions. The term
      encompasses more than 80 different pathologically defined tumors of the soft
      tissue. Every year, nearly 4000 patients are affected in Germany. The diversity
      and rarity of the disease make progress difficult. The average 5-year mortality
      is around 40 %. Therapy is stage-adapted based on size, grading, localization,
      involvement of lymph nodes or distant metastasis. In the localized situation,
      surgery is the basis of therapy. Standard is the wide resection. Depending on
      grading, degree of resection and localization, adjuvant radiotherapy follows in
      the case of so-called high-risk tumors. Certain very aggressive types (so-called
      small, blue, round cell sarcomas such as embryonal rhabdomyosarcomas, Ewing
      tumors, PNET and desmoplastic soft tissue sarcomas (desmoplastic small round cell
      tumors) are primarily treated with systemic treatment in a multimodality setting.
      Metastasis surgery is established in isolated pulmonary metastases based on
      retrospective studies. This article focuses on recent development in treatment of
      adult type soft tissue sarcoma and GIST.

PMID- 30286492
TI  - [Shortened duration of antibiotic therapy in bacterial infections].
AB  - The adequate duration of antibiotic therapy in the treatment of bacterial
      infections is often unclear. For many indications guidelines recommend intervals
      with ranges of several days instead of fixed courses of treatment, and physicians
      tend to choose longer rather than shorter durations. The emergence of infections
      due to multidrug-resistant bacteria and the valuation of avoidable side effects
      from antibiotic agents raised the question whether a shortened duration of
      therapy is appropriate in specific indications. Therefore clinical trials to
      investigate the effectiveness of shorter in comparison to prolonged antibiotic
      treatment have yet been of growing interest to current research. Recent studies
      have shown that, concerning clinical endpoints, shorter duration of antibiotic
      therapy is not inferior to longer treatment in the management of pyelonephritis,
      intraabdominal infections, community acquired pneumonia an also gramnegative
      bloodstream infections and febrile neutropenia.

PMID- 30286493
TI  - [Do Vitamins Play a Role in the Pathogenesis and Therapy of Sepsis?]
AB  - Hospital mortality of severe sepsis and septic shock is still around 40 %
      according to recent studies. In accordance to the current sepsis definition,
      sepsis is a life-threatening organ dysfunction caused by a dysregulated response
      of the organism to infection. Septic shock is defined by vasopressor-dependent
      circulatory failure and lactic acidosis. Patients with sepsis and septic shock
      are often old and/or characterized by severe comorbidities, e. g. tumor or liver
      disease. These factors also predispose to malnutrition and hence to a
      corresponding deficiency of essential nutritional components e. g. vitamins. A
      number of recent studies and reviews have addressed the question whether
      deficiencies in certain vitamins may facilitate the transition from infection to
      septic shock. In addition, studies have investigated the effect of high-dose
      vitamin therapies on sepsis mortality and sepsis-associated organ dysfunctions.
      This article would like to summarize this current discussion with a focus on
      vitamin B1 (thiamine), vitamin C and vitamin D.

PMID- 30286494
TI  - [Update ESC-Guideline 2017: Focus on PAD].
AB  - The updated ESC guidelines on PAD were developed, for the first time, as a
      collaboration between cardiologists and vascular surgeons and unveiled at the
      European Society of Cardiology (ESC) 2017 congress. Although awareness has
      improved, PAD is still associated with significant morbidity, mortality, and
      quality of life impairment. Primarily, the guidelines emphasize the need for a
      multidisciplinary management of these patients and propose "a vascular team". A
      new chapter on antithrombotic therapies is provided. In patients with symptomatic
      peripheral artery disease, clopidogrel can be considered over aspirin therapy
      (class IIb). Antiplatelet therapy is no longer recommended in asymptomatic
      peripheral artery disease patients (class III). After peripheral arterial
      intervention, dual antiplatelet therapy is recommended as a consensus. Moreover,
      all patients with lower extremity artery disease should be treated with statins
      to improve walking distance (class I) as well as supervised exercise therapy,
      even after revascularization. In claudicants, cardiovascular prevention and
      exercise training remain the cornerstones of management. The WIFI classification
      (risk stratification based on wound ischemia and foot infection) is proposed to
      primarily describe wound lesions. Regarding surgical or interventional therapies,
      the new guidelines propose an endovascular approach for short lesions (< 5 cm) in
      the aortoiliac or aortobifemoral region. Patients with infrapopliteal lesions
      should be treated with bypass surgery or endovascular therapy. Patients with
      coronary artery disease or heart failure should be considered for lower extremity
      peripheral artery disease screening (class IIb).

PMID- 30286495
TI  - [Update on Diabetic Nephropathy 2018].
AB  - UPDATE ON DIABETIC NEPHROPATHY 2018:  The prevalance of elevated albuminuria in
      patients with diabetes is decreasing, while that of reduced eGFR is increasing,
      probably owing to more stringent blood pressure and blood glucose control.Well
      validated online score calculators for risk for renal replacement therapy,
      cardiovascular events and death are available online.Clinical variables remain
      more suited than histology for predicting end stage renal disease. Extracapillary
      hypercellularity, segmental sclerosis and exsudative lesions could represent a
      distinct risk phenotype.SGLT-2-inhibitors and GLP-1 analogues provide significant
      reductions of micro- and macrovascular end points. SGLT-2-inhibitors can only be
      prescribed at eGFR > 60 ml/min/1,73 m2, GLP-1 analogues and metformin at eGFR >
      30 ml/min/1,73 m2.The ACC/AHA guideline 2017 defines arterial hypertension at
      blood pressure >= 130/80 mmHg, the ESC/ESH guideline 2018 at >= 140/90 mmHg. The
      blood pressure goal for patients with diabetes is < 130/80 mmHg, if well
      tolerated. ESC/ESH 2018 recommend not lowering blood pressure lower than 120/70
      mmHg, in persons aged >= 65 years, systolic blood pressure 130 - < 140 mmHg is
      recommended.

PMID- 30286496
TI  - [Sleep Apnea].
AB  - In 2017 the German Sleep Society (Deutsche Gesellschaft fur Schlafforschung und
      Schlafmedizin, DGSM) published the new S3 guideline "Nonrestorative Sleep/Sleep
      Disorders, chapter "Sleep-Related Breathing Disorders in Adults".Sleep apnea
      contributes to an increased morbidity and mortality in patients with
      cardiovascular diseases, e. g. coronary heart disease, heart failure and diabetes
      mellitus and is associated with an increased perioperative risk. It is also an
      important comorbidity in respiratory, neurologic and oncologic diseases.
      Treatment of sleep apnea can improve daytime sleepiness, quality of life und
      reduce blood pressure. In patients with atrial fibrillation, obstructive sleep
      apnea treatment should be optimized to improve treatment results. In addition to
      CPAP (continuous positive airway pressure) therapy and mandibular advancement
      devices, there are new therapies (e. g. hypoglossal nerve stimulation).
      Telemonitoring can help to improved therapy adherence. Nevertheless, in a current
      study CPAP could not prevent cardiovascular events in patients with moderate-to
      severe obstructive sleep apnea and established cardiovascular disease. Patients
      with predominantly central sleep apnea and systolic hear failure (left
      ventricular ejection fraction <= 45 %) had an increased cardiovascular mortality
      when treated with adaptive servoventilation. Therefore, ASV is contraindicated in
      this small group of patients. Further studies are ongoing.

PMID- 30286497
TI  - [Recent Developments in Myositis Syndromes].
AB  - Idiopathic inflammatory myopathies (IIM) are a rare and clinically polymorphic
      and heterogenous group of myositis syndromes. Myositis is part of a systemic
      autoimmune disorder with various extramuscular manifestations affecting skin,
      lungs, joints, esophagus and other organ systems. Most myositis patients have
      autoantibodies against non organspecific antigens. More than 20 different
      autoantibodies are known. They are associated with different clinical phenotypes
      of adult or juvenile dermatomyositis or myositis-overlap syndromes and different
      genetic markers. Pure polymyositis, if not a monosymptomatic manifestation of a
      systemic disorder, so far has no marker antibody and is an exclusion diagnosis.
      Sporadic inclusion body myositis (sIBM) has no extramuscular manifestations, cN1A
      antibodies are directed against muscle-derived antigen and are not highly
      specific for IBM.Myositis syndromes differ in histopathology. Patients with anti
      synthetase-syndrome frequently have necrotizing perifascicular myositis with
      myonuclear actin inclusions.New classification criteria have been developed by
      the European (EULAR) and American (ACR) rheumatology societies and different
      outcome measurements for clinical studies are now available.There is still a lack
      of controlled therapeutic trials. However there is good consensus that
      glucocorticosteroids (GC) are necessary and effective to treat active myositis
      usually in combination with methotrexate or azathioprine. Rituximab is effective
      in GC-resistant myositis as well as high dose i. v. immune globulin (IVIG) in
      certain conditions.

PMID- 30286498
TI  - [Practical Genetic Testing in Gastroenterology].
AB  - Genetic testing has become increasingly relevant in daily clinical practice due
      to the identification of susceptibility genes for several diseases. This article
      focuses on genetic testing for hereditary pancreatitis, inflammatory bowel
      disease and fatty liver disease. Several genetic variants that contribute to
      chronic pancreatitis development have been identified. If the individual
      aetiology of chronic pancreatitis is unclear, genetic testing for common
      predisposing variants should be offered. Inflammatory bowel diseases are complex
      and multifactorial disorders. However, rare mono- or oligogenic forms of disease
      exist and should be screened for, as personalized therapies can be offered to
      subsets of these patients. Genetic risk factors also promote the manifestation
      and progression of fatty liver disease, liver cirrhosis and hepatocellular
      carcinoma. In conclusion, genetic testing plays an increasing role in delineating
      the pathogenesis of gastroenterological and hepatic diseases, in the
      stratification of patients at risk for severe disease complications, and in the
      optimization of patient care.

PMID- 30286499
TI  - [Optical Coherence Tomography in Non-ST-Segment Elevation Myocardial Infarction].

PMID- 30286500
TI  - [Papillary Fibroelastoma of the Pulmonary and Tricuspid Valve in Asymptomatic
      Patients].
AB  - HISTORY:  Case 1: admission to hospital of a 72-year-old male patient due to
      suspect tumor at the pulmonary valve. At admission the patient was
      hemodynamically stable with known coronary one vessel heart disease and arterial
      hypertension.Case 2: admission to hospital of a 74-year-old female patient due to
      symptoms of de novo angina pectoris with known coronary three vessel heart
      disease. FINDINGS AND DIAGNOSIS:  In both patients suspect tumors could have been
      detected at the pulmonary- and tricuspid valve by transthoracic echocardiography.
      In case 1 coronary angiography showed a complex coronary three vessel heart
      disease with indication for surgery. In case 2 coronary angiography showed a
      subtotal stenosis of the RCA which could have been treated by percutaneous
      coronary intervention (PCI). THERAPY AND COURSE:  In both cases the tumor were
      highly suspective to be benigne. Despite of the certain risk of embolism, surgery
      was only recommended in case 1 because the patient needed surgical
      revascularisation anyway due to the complex coronary three vessel heart disease.
      In case 2 the RCA stenosis has been treated by PCI and surgery has not been
      recommended. CONCLUSIONS:  Echocardiography can help to detect cardiac tumors
      whereas the diagnosis can only be confirmed by biopsy. Further therapeutic
      procedures should be defined individually.

PMID- 30286501
TI  - Regular Physical Activity and Risk of Venous Thromboembolism.
AB  - Venous thromboembolism (VTE) is a complex multifactorial disease that represents
      a growing public health concern. Identification of modifiable risk factors at the
      population level may provide a measure to reduce the burden of VTE. In this
      review, we summarize current knowledge of the role of physical activity on the
      risk of VTE and VTE-related complications. We also discuss methodological
      challenges related to research on physical activity, and put forward plausible
      mechanisms for an association between physical activity and VTE. Up to now,
      published studies have reported diverging results on the relationship between
      physical activity and VTE, and a complex picture has emerged. However, the
      available evidence appears to be balanced toward a small beneficial effect of
      physical activity on the risk of incident VTE, but not in a dose-dependent
      manner. Still, the lack of an operational definition and standardized assessment
      method for physical activity, as well as several sources of bias, impairs the
      interpretation of the available literature. Additional work is necessary to
      understand the role and how to apply physical activity in the VTE setting. Future
      research should utilize objective assessment strategies of physical activity and
      physical fitness, account for the fluctuating nature in habitual activity levels,
      and explore the role of physical activity in the areas of secondary prevention
      and VTE-related complications.

PMID- 30286502
TI  - Impact of Exercise/Sport on Well-being in Congenital Bleeding Disorders.
AB  - Physical activity provides many benefits in patients with congenital bleeding
      disorders. Patients with hemophilia are encouraged to participate in exercise and
      sports, especially those patients receiving prophylaxis. Several publications and
      guidelines have explored this issue in hemophilia patients, evaluating in
      particular the impact of physical activity on patients' well-being and quality of
      life. The other rare congenital bleeding disorders are less studied; they are
      heterogeneous in terms of clinical bleeding phenotype, incidence of hemarthrosis,
      and arthropathy. Furthermore, prophylaxis in these patients is less common than
      in hemophilia patients, which must be considered when choosing the type of
      physical and sporting activity. In this review, the authors have analyzed the
      literature focusing their attention on those rare coagulation disorders that may
      be complicated by arthropathy and the role of exercise and sports in this
      context.

PMID- 30286503
TI  - Acquired and Genetic Thrombotic Risk Factors in the Athlete.
AB  - While athletes are often considered the epitome of health due to their physique
      and lowered potential for metabolic and cardiovascular diseases, they may also be
      at risk for the onset and development of venous thromboembolism (VTE). In an
      attempt to achieve and remain competitive, athletes are frequently exposed to
      numerous athlete-specific risk factors, which may predispose them to VTE through
      the disruption of factors associated with Virchow's triad (i.e.,
      hypercoagulability, venous stasis, and vessel wall injury). Indeed,
      hypercoagulability within an athletic population has been well documented to
      occur due to a combination of multiple factors including exercise, dehydration,
      and polycythemia. Furthermore, venous stasis within an athletic population may
      occur as a direct result of prolonged periods of immobilization experienced when
      undertaking long-distance travels for training and competition, recovery from
      injury, and overdevelopment of musculature. While all components of Virchow's
      triad are disrupted, injury to the vessel wall has emerged as the most important
      factor contributing to thrombosis formation within an athletic population, due to
      its ability to influence multiple hemostatic mechanisms. Vessel wall injury
      within an athletic population is often related to repetitive microtrauma to the
      venous and arterial walls as a direct result of sport-dependent trauma, in
      addition to high metabolic rates and repetitive blood monitoring. Although
      disturbances to Virchow's triad may not be detrimental to most individuals,
      approximately 1 in 1,000 athletes will experience a potentially fatal post
      exercise thrombotic incidence. When acquired factors are considered in
      conjunction with genetic predispositions to hypercoagulability present in some
      athletes, an overall increased risk for VTE is present.

PMID- 30286504
TI  - [Risks and Side Effects of Psychotherapy].

PMID- 30286505
TI  - [Definition and Decision-Making in the Determination and Detection of Side
      Effects of Psychotherapy].
AB  - There is no generally accepted definition of side effects, which causes problems
      in research and clinical practice. Not even the distinction between main and side
      effects is always clear. Several judgments are needed in the assessment of side
      effects. First, it must be decided where to look for unwanted events. Events are
      defined by the temporal contingency with the treatment. Second, it must be made a
      judgement whether it is an unwanted or wanted event. Everything is unwanted,
      which would be problematic, if it would be possible to do without it. Thirdly, a
      causal relationship with the treatment must be made plausible. Fourthly, a
      decision must be made that the treatment has been adequate and not malpractice or
      other unethical behavior. Side effects can be defined as unwanted consequences of
      correct treatment. The relevance of side effects is depending on severity and
      duration.

PMID- 30286506
TI  - [CBASP as an Inpatient Concept for Treatment-Resistant Chronic Depression: A
      Pilot Study of the Relationship between Adverse Effects and Treatment Outcome].
AB  - BACKGROUND: Inpatient psychotherapy might trigger adverse effects among others
      due to short but intensive treatment. Thus, in this pilot study, certain adverse
      effects of the multidisciplinary inpatient Cognitive Behavioral Analysis System
      of Psychotherapy (CBASP) for treatment-resistant chronically depressed patients
      as well as their relationship to treatment outcome (response-, remission-, and
      relapse-rates) are examined. MATERIAL AND METHODS: 50 patients with treatment
      resistant and chronic depression completed the structured 12-weeks inpatient
      treatment program. Adverse effects were assessed by 1) deterioration of
      depressive symptoms (measured by the Hamilton Depression Rating Scale, HDRS) at
      discharge and 2) a self-report questionnaire measuring Adverse Effects of
      Inpatient Psychotherapy (ADEFIP), which were filled out 6 to 12 months after
      discharge by the patients. RESULTS: After 12 weeks of treatment, 84% could be
      classified as responder, of whom 44% fulfilled the remission criterion. 16% were
      Non-Responder. According to HDRS, none of the patients showed objective
      deterioration of the depressive symptoms. Six months after discharge, 40% of the
      responders suffered from relapse. Concerning the ADEFIP, 66% of the patients
      reported transient deterioration of symptoms. These patients were less likely to
      achieve remission. Over 50% reported interpersonal conflicts with treatment team
      members or other patients without any relation to outcome. Finally, more than
      half of the patients reported significant changes in social relationships after
      discharge. These patients were less likely to relapse. Overall, 94% of the
      patients reported at least one of the in this study assessed adverse effects.
      CONCLUSIONS: Despite some limitations, this pilot study suggests that the CBASP
      inpatient program could indeed cause adverse effects. However, only subjective
      transient deterioration appeared to have a negative impact on the individual
      treatment outcome in the short-term. Results encourage further research
      concerning adverse treatment effects in the context of short- and long-term
      treatment outcome investigating how relevant adverse effects are.

PMID- 30286507
TI  - [Negative Indicators in the Psychotherapeutic Process: Frequency and Relationship
      with Attachment Characteristics and Treatment Outcome among Patients with Social
      Anxiety Disorder].
AB  - Within the SOPHO-Net-Project, mainly focusing on a randomized-controlled trial
      comparing short term cognitive and psychodynamic psychotherapy for social anxiety
      disorder, a subsample consisting of 88 patients from 3 of the 5 study sites was
      investigated to examine the relationship between outcome, initial attachment
      characteristics and negative indicators during the process. These negative
      indicators were assessed with the Vanderbilt Negative Indicators Scale which was
      applied to an early (3rd), a middle (9th) as well as a late therapy (22nd)
      session. The study shows that negative indicators as a whole were relatively rare
      with a higher frequency within the psychodynamic therapies for which a
      relationship between negative indicators and outcome could be found. Contrary to
      expectation, initial attachment characteristics were not related to negative
      indicators.

PMID- 30286508
TI  - [Complains about Psychotherapy and their Impact on Patients].
AB  - Unprofessional psychotherapy damages its otherwise good standing. For that
      reason, a public discussion about malpractice and unethical psychotherapist
      behavior is oftentimes missing even though addressing the topic openly could
      illustrate its rarity and promote a professional handling of psychotherapeutic
      misconduct. In the presented study, qualitative content analysis was conducted to
      analyze malpractice claims that were sent to the Psychotherapeutic Chamber of
      North Rhine-Westphalia (Germany) in 2011 and 2012. All letters were anonymized
      and the processing of the claims was completed. In total, 149 relevant
      malpractice claims and 124 statements about consequences of malpractice behaviors
      were identified. Most malpractice claims were related to the category "violation
      of therapeutic basic variables" (40.3%), followed by "violation of general
      conditions" (16.8%) and "financial abuse" (12.1%). In consequence, 28.2% of the
      patients described a "deterioration of their symptoms". These results shed light
      on the variation of existing malpractice claims and their consequences for
      patients indicating the need for awareness-raising actions for therapists and
      patients.

PMID- 30286509
TI  - [First Experiences with the "Questionnaire for the Assessment of Side Effects and
      Negative Experiences in Group Therapy" (NUGE-24)].
AB  - This report describes the development of a questionnaire aiming in assessing
      unwanted effects of group psychotherapy and side effects of the group setting.
      Based upon interviews with experts and considering a model differentiating group
      related, therapist related strain within groups, stress caused by other members
      and subjective excessive demands, a first version of the questionnaire was
      developed and tested in the clinical field using heterogeneous groups. The data
      set from this sample (N=168 patients) was used to construct a 24-item short
      version with 6 items per scale reflecting the 4 contents. A first comparison of
      different groups related to unwanted experiences and side effects indicates that
      the NUGE-questionnaire might be useful in differentially assessing these effects.
      This should now be tested in more systematic studies.

PMID- 30286510
TI  - An Electrophilic Bromine Redox Catalysis for the Synthesis of Indole Alkaloid
      Building Blocks by Selective Aliphatic C-H Amination.
AB  - A new homogeneous bromine(-I/I) redox catalysis is described, which is based on
      monomeric bromine(I) compounds containing transferable phthalimidato groups.
      These catalysts enable intermolecular C-H amination reactions at previously
      unaccessible aliphatic positions and thus enlarge the synthetic potential of
      direct C-N bond formation, including its application in the synthesis of alkaloid
      building blocks. This aspect is demonstrated by a new synthetic approach to
      aspidospermidine. In addition to the development of the catalyst system, the
      structures of the involved bromine(I) key catalysts were fully elucidated,
      including by X-ray analyses.

PMID- 30286511
TI  - Anthocyanidines structural study using positive electrospray ionization triple
      quadrupole mass spectrometry and H/D exchange.
AB  - We report herein a detailed structural study by collision-induced dissociation
      (CID) of non-glycosylated anthocyanins (anthocyanidines) using electrospray
      ionization triple quadrupole mass spectrometry (ESI-QqQ) and isotope labeling
      experiments to understand the fragmentation process often used in mass
      spectrometry analysis of this class of compounds. Tandem mass spectrometric
      product ion spectra for three anthocyanidines (cyanidin, delphynidin, and
      pelargonin) were evaluated to propose fragmentation mechanisms to this natural
      colorant class of organic compounds. The proposed rearrangements, retro Diels
      Alder reaction, water loss, CO losses, and stable acylium ion formation, were
      evaluated based on tandem mass spectrometric experiments of normal and labeled
      precursor ions together to computational thermochemistry. B3LYP/6-311+G** ab
      initio calculations studies were carried out to obtain energy diagrams to show
      the viability of the proposed mechanisms. The CO losses fragmentation channels
      have lower energies when compared to water losses, and the other proposed
      fragmentations. The isotope labeling experiments indicate the H/D exchange of the
      hydroxyl protons and corroborate the proposed general fragmentation mechanism for
      anthocyanidins.

PMID- 30286512
TI  - Validation of Quantitative Microbial Risk Assessment Using Epidemiological Data
      from Outbreaks of Waterborne Gastrointestinal Disease.
AB  - The assumptions underlying quantitative microbial risk assessment (QMRA) are
      simple and biologically plausible, but QMRA predictions have never been validated
      for many pathogens. The objective of this study was to validate QMRA predictions
      against epidemiological measurements from outbreaks of waterborne
      gastrointestinal disease. I screened 2,000 papers and identified 12 outbreaks
      with the necessary data: disease rates measured using epidemiological methods and
      pathogen concentrations measured in the source water. Eight of the 12 outbreaks
      were caused by Cryptosporidium, three by Giardia, and one by norovirus. Disease
      rates varied from 5.5 * 10-6 to 1.1 * 10-2 cases/person-day, and reported
      pathogen concentrations varied from 1.2 * 10-4 to 8.6 * 102 per liter. I used
      these concentrations with single-hit dose-response models for all three pathogens
      to conduct QMRA, producing both point and interval predictions of disease rates
      for each outbreak. Comparison of QMRA predictions to epidemiological measurements
      showed good agreement; interval predictions contained measured disease rates for
      9 of 12 outbreaks, with point predictions off by factors of 1.0-120 (median =
      4.8). Furthermore, 11 outbreaks occurred at mean doses of less than 1 pathogen
      per exposure. Measured disease rates for these outbreaks were clearly consistent
      with a single-hit model, and not with a "two-hit" threshold model. These results
      demonstrate the validity of QMRA for predicting disease rates due to
      Cryptosporidium and Giardia.

PMID- 30286513
TI  - Sudden Unexplained Nocturnal Death Syndrome: Epidemiological and Morphological
      Characteristics in Thai Autopsy Cases.
AB  - With limited knowledge on epidemiological and morphological characteristics of
      sudden unexplained nocturnal death syndrome (SUNDS), this study was aimed to
      identify such data in Thai SUNDS autopsy cases. All the cases were men and
      nondrug abusers aged 20-49 years old. Most cases were originated in the
      Northeastern region of Thailand. Half of them were found dead from midnight to 6
      a.m., with a peak time at 2 a.m. The death rate was relatively higher in May and
      June. Most SUNDS cases were blue-collar workers (93.2%) and nonsmokers (60%),
      with a normal BMI (72.1%). Approximately one-fifth of the cases had detectable
      blood alcohol concentrations. Symptoms before death were respiratory difficulty,
      seizures, and urinary incontinence. Their mean heart weight was 329.8 +/- 35.1 g.
      Their lungs (88.6%) had some degree of congestion. Acute pancreatitis was not
      found in these SUNDS cases, and approximately half (40.9%) of the cases had their
      gastric content <100 mL.

PMID- 30286514
TI  - Exploring the relationship between the body self and the sense of coherence in
      women after surgical treatment for breast cancer.
AB  - OBJECTIVE: Analysis of the relationship between the body self (BS) and the sense
      of coherence (SOC) in women after breast surgery due to cancer in comparison with
      a control group. METHODS: A cross-sectional study in a group of 78 women using
      the body-self questionnaire (BS-Q), and the life orientation questionnaire (SOC
      29). Statistics based on the IBM SPSS v.25. RESULTS: Multivariate analysis of
      variance (MANOVA) has shown significant differences based on groups in
      experiencing intimacy, manifesting femininity, body acceptance, and
      manageability. In particular, manifesting femininity and body acceptance showed a
      big effect size (0.30 < partial n2  < 0.32). Correlation analysis between the BS
      Q and SOC-29 subscales and Fisher's r to z transformation determines that the
      differences between groups were significant in favour of healthy women in two
      sets of variables: experiencing intimacy/meaningfulness and attitude to food and
      weight/manageability. CONCLUSIONS: Breast cancer survivors are at greater risk of
      developing decreased body acceptance and problems in intimacy, and have less
      correlation than the healthy control group between manageability and
      meaningfulness with an appropriate attitude to food and intimate relationship
      with their partner, respectively. A higher manifestation of femininity in the
      treated group can be considered a positive but socioculturally conditioned coping
      strategy.

PMID- 30286516
TI  - Outcome of cell suspension allografts in a patient with Huntington's disease.
AB  - For patients with incurable neurodegenerative disorders such as Huntington's (HD)
      and Parkinson's disease, cell transplantation has been explored as a potential
      treatment option. Here, we present the first clinicopathological study of a
      patient with HD in receipt of cell-suspension striatal allografts who took part
      in the NEST-UK multicenter clinical transplantation trial. Using various
      immunohistochemical techniques, we found a discrepancy in the survival of grafted
      projection neurons with respect to grafted interneurons as well as major ongoing
      inflammatory and immune responses to the grafted tissue with evidence of mutant
      huntingtin aggregates within the transplant area. Our results indicate that
      grafts can survive more than a decade post-transplantation, but show compromised
      survival with inflammation and mutant protein being observed within the
      transplant site. Ann Neurol 2018; 1-7.

PMID- 30286515
TI  - Anatomic and procedural associations of transcatheter heart valve displacement
      following Evolut R implantation.
AB  - OBJECTIVES: This study aimed to predict the displacement of self-expanding
      transcatheter heart valves (THV) during final deployment. BACKGROUND: Accurate
      device positioning during transcatheter aortic valve implantation (TAVI) is
      crucial for optimal results. METHODS: At our institution, 103 patients who
      underwent transfemoral TAVI with Evolut R were retrospectively identified.
      Multiple linear regression models were created, and a predictor equation was
      built to quantify the factors that may affect THV behavior. RESULTS: Multiple
      linear regression analysis for THV displacement on the left coronary cusp (LCC)
      identified the angle between the THV and the ascending aorta (ATA), predilation,
      and less operator experience as independent predictors of upward displacement,
      whereas estimated glomerular filtration rate (eGFR) was inversely related with
      THV behavior (95% confidence interval: 0.219 to 0.340, 0.447 to 2.092, 0.165 to
      1.757, and -0.053 to -0.011, respectively). Predictors of THV displacement on the
      noncoronary cusp side could not be identified using this model. CONCLUSIONS: The
      ATA at the point of recapture, predilation, and less operator experience were
      independent predictors of upward displacement of THV on the LCC side. eGFR was an
      independent predictor of THV downward displacement on the LCC side. Of them, the
      ATA was the strongest predictor. Physicians may need to adjust this angle
      adequately before deployment to achieve the appropriate position.

PMID- 30286517
TI  - A [11 C] CO dispensing system for rapid screening of carbonylation reactions.
AB  - [11 C] CO is a highly versatile synthon that allows for labeling at carbonyl
      positions of many molecules by means of transition metal-mediated carbonylation
      reactions. The intrinsic complexity of carbonylation reactions often requires
      tedious screening of reaction conditions for obtaining satisfying yields. Herein,
      a [11 C] CO dispending system for performing multiple reactions with a single
      batch of cyclotron-produced [11 C]CO2 is described. This semiautomated setup
      allows for more rapid and efficient screening of reactions and reaction
      conditions compared with the traditional "one beam for one reaction" strategy.

PMID- 30286518
TI  - Making Sense of Risk-A Sociological Perspective on the Management of Risk.
AB  - This article describes how risk has been conceptualized in the business and
      organizational literature through four distinct transformations: from the techno
      scientific perspective to the cognitive, the social-cultural, and, finally, to
      the constructionist perspective. Each domain conceptualizes risk in different
      ways, as organizations have found it difficult to understand and mitigate using
      the risk management tools available. Conceptualizing risk as sensemaking becomes
      relevant due to the complexity of information available to the risk manager, and,
      coupled with time constraints, this means that risk managers increasingly rely on
      making sense of possible threats rather than on the accuracy of the information
      received. This shift presents four contributions to the current literature.
      First, it suggests that the role of risk management is shifting from being
      technical in nature to being about risk sensemaking, where the manager engages
      with the social and physical environment with the aim of acquiring cues that
      could indicate how future events will unfold. Second, a sensemaking perspective
      implies a shift in the use of risk management systems from being "containers" of
      knowledge about past risk events to lending legitimacy to the plausibility of the
      success of future decisions. Third, the role of the risk manager in managing
      individual risks changes and becomes one of managing everything using the social
      networks and systems available as indicators of future risk events. Finally, the
      risk manager and the systems he or she relies upon are regarded as a source of
      risk in themselves as both act as gatekeepers for organizational risk decision
      making.

PMID- 30286519
TI  - Planning percutaneous coronary interventions using computed tomography
      angiography and fractional flow reserve-derived from computed tomography: A state
      of-the-art review.
AB  - Fractional flow reserve derived by coronary computed tomography angiography (CTA;
      FFRCT) is an accurate noninvasive method for identifying coronary artery disease
      (CAD) and detecting hemodynamically significant stenosis. Although initially
      proposed as noninvasive tools to "rule out" significant CAD in low-risk patients,
      CTA and FFRCT are now utilized in higher-risk patients. Furthermore, new
      applications of CTA and FFRCT include a planning tool for percutaneous coronary
      intervention (PCI), which allows the cardiologist to assess lesion-specific
      ischemia, plan stent locations and sizes, and use virtual remodeling of the lumen
      (virtual stenting) to assess the functional impact of PCI. The purpose of this
      review is to discuss the principles of CTA and FFRCT acquisition, and their
      application for PCI planning, even before invasive angiography is performed.

PMID- 30286520
TI  - Three-year clinical outcomes of patients treated with everolimus-eluting
      bioresorbable vascular scaffolds: Final results of the ABSORB EXTEND trial.
AB  - BACKGROUND: There is still limited data on the very long term clinical outcomes
      after ABSORB BRS in daily practice. We sought to evaluate the 3 year-performance
      of the Absorb bioresorbable vascular scaffolds for the treatment of low/moderate
      complexity patients enrolled in the ABSORB EXTEND trial. METHODS: ABSORB EXTEND
      is a prospective, single-arm, open-label clinical study in which 812 patients
      were enrolled at 56 sites. This study allowed the treatment of lesions <=28 mm in
      length and reference vessel diameter of 2.0-3.8 mm (as assessed by on-line QCA).
      To determine the independent predictors of MACE, a multivariable logistic
      regression model was built using a stepwise (forward/backward) procedure.
      RESULTS: Average population age was 61 years and 26.5% had diabetes. Most
      patients had single target lesion (92.4%). Adequate scaffold deployment (PSP) was
      achieved in 14.2% of the cases. At three years, the composite endpoints of MACE
      and ischemia-driven target vessel failure were 9.2% and 10.6%, respectively. The
      cumulative rate of ARC definite/probable thrombosis was 2.2%, with 1.2% of the
      cases occurring after the 1st year. Independent predictors of MACE were
      hypertension and the need for "bail out" stent. CONCLUSION: At three-year follow
      up, the use of ABSORB in low/moderate complex PCI was associated with low and
      acceptable rates of major adverse clinical events, despite the infrequent use of
      the recommended contemporary scaffold deployment technique. However, scaffold
      thrombosis rate was higher than reported with current generation of metallic DES.
      The study is registered on clinicaltrials.gov (unique identifier NCT01023789).

PMID- 30286521
TI  - Predictive Value of Quantitative Uterine Fibroid Perfusion Parameters From
      Contrast-Enhanced Ultrasound for the Therapeutic Effect of High-Intensity Focused
      Ultrasound Ablation.
AB  - OBJECTIVES: To assess the predictive significance of quantitative perfusion
      parameters from contrast-enhanced ultrasound (CEUS) for the therapeutic response
      to high-intensity focused ultrasound (HIFU) ablation in patients with uterine
      fibroids. METHODS: A total of 263 patients with single uterine fibroids were
      treated with HIFU ablation under ultrasound guidance. The arrival time, peak
      time, enhancement time, enhancement intensity, and enhancement rate were
      evaluated with pretreatment CEUS. According to a nonperfused volume ratio
      evaluation by posttreatment magnetic resonance imaging, all patients were
      assigned to groups with volume ratios of 70% or higher and lower than 70%. Then
      the predictive performances of different parameters for ablation efficacy were
      studied. RESULTS: The arrival time, peak time, and enhancement time in the group
      with a nonperfused volume ratio of 70% or higher were longer than those in the
      group with a volume ratio lower than 70% (mean +/- SD, 16.7 +/- 3.5, 26.5 +/-
      4.9, and 10.2 +/- 2.6 seconds, respectively, versus 13.3 +/- 4.2, 20.8 +/- 5.4,
      and 7.6 +/- 2.3 seconds), whereas patients with a volume ratio of 70% or higher
      had a lower mean enhancement intensity and enhancement rate than those with a
      volume ratio lower than 70% (29.7 +/- 16.7 dB and 3.2 +/- 1.5 dB/s versus 63.2 +/
      26.3 dB and 8.6 +/- 4.3 dB/s; P < .05). The nonperfused volume ratio was
      negatively correlated with the enhancement intensity and enhancement rate (r = 
      0.631 and -0.712) but positively correlated with the arrival time, peak time, and
      enhancement time (r = 0.322, 0.456, and 0.477; P < .05). The areas under the
      receiver operating characteristic curve for the enhancement time, enhancement
      intensity, and enhancement rate were 0.73, 0.79, and 0.81 (P < .05). CONCLUSIONS:
      Quantitative parameters from CEUS are potentially useful for evaluating the
      therapeutic effect of HIFU ablation for uterine fibroids.

PMID- 30286522
TI  - Distress predicts utilization of psychosocial health services in oncology
      patients.
AB  - OBJECTIVE: The prevalence of increased distress among cancer patients has been
      well established and is known to be associated with negative consequences.
      Limited research has examined the association between distress and utilization of
      services, however, which is critical to understanding whether measurements of
      distress are being used to optimize patient care in the context of cancer.
      METHODS: One thousand two hundred thirteen adult cancer patients completed the
      Distress Thermometer and Patient Needs Assessment early in their cancer care.
      Electronic medical record (EMR)-abstracted data included psychosocial service
      utilization in the 12 months following the completion of these psychosocial
      metrics. Logistic regressions followed by t tests were completed to assess if
      distress or unmet needs were affiliated with service utilization rates. RESULTS:
      When controlling for age, distress significantly predicted service utilization
      rates overall. Follow-up t tests suggest that use of social work and registered
      dietician services was higher among those with distress scores greater than 6.
      When assessing unmet needs, utilization rates were positively associated with
      number of unmet needs, specifically for social work and dieticians. CONCLUSIONS:
      Distress and unmet needs were related to higher rates of psychosocial service
      utilization during the 12 months following assessment of symptoms. These results
      support the continued mandate for evaluation of distress and suggest that
      psychosocial screening may be assisting in directing referrals and enhancing
      comprehensive care for patients. As psychosocial services grow, the need for
      continued evaluation is recommended to determine if psychology and chaplaincy
      services are utilized at higher rates as available providers increase.

PMID- 30286523
TI  - Using micro computed tomography to investigate a fetal mummy with possible situs
      inversus: A case report.
AB  - OBJECTIVES: Computed tomography (CT) is commonly used to noninvasively examine
      mummified remains, but can have resolution limitations when analyzing smaller
      mummified specimens, such as fetal mummies. This short report determines if the
      enhanced resolution of micro CT improves the anatomical analysis of mummified
      fetal anatomy. METHODS: A fetal mummy from an anatomical collection was scanned
      by a micro CT at a resolution of 0.08 mm slice thickness. The mummy was also
      scanned at a resolution of 0.6 mm slice thickness to mimic the approximate
      minimum resolution of a conventional CT scanner. The anatomy was virtually
      reconstructed at both resolutions to compare anatomical detail for determining
      sex, gestation, and the presence of congenital/ pathological conditions. RESULTS:
      The anatomical reconstructions based on the micro CT were significantly more
      detailed than the conventional CT data. This resulted in improved identification
      of sex and the presence of a congenital/ pathological condition. CONCLUSION:
      Micro CT should be considered when examining fetal mummies, because of the
      enhanced resolution resulting in improve anatomical analysis.

PMID- 30286524
TI  - Global country-level estimates of associations between adult height and the
      distribution of income.
AB  - OBJECTIVES: This article presents the first estimates of global associations
      between adult height and the distribution of income, and considers the roles of
      regional heterogeneity, heterogeneity across low- and high-income countries, and
      of infant mortality as a potential mediator. METHODS: Linear parametric and
      semiparametric regressions predicting mean height and sexual dimorphism in height
      are estimated using data on one cohort born in 1996 with height measured in 2016.
      Measurement error in income inequality is addressed using an instrumental
      variables method. RESULTS: Across countries higher income per capita is strongly
      associated with higher mean height, and higher income inequality is associated
      with lower mean height after holding mean income constant. These relationships
      vary with mean income: at low incomes, higher mean income strongly predicts
      greater height but income inequality has no statistically significant effect,
      whereas for high-income countries, only higher income inequality predicts lower
      height, and only in Europe. Sexual dimorphism in height is positively associated
      with mean income at low incomes, but it is not related to income inequality.
      CONCLUSIONS: Controlling for income inequality has modest effects on a positive
      height-income gradient. Greater inequality predicts lower height after holding
      income per capita constant, suggesting that mean height should be used with
      caution as a proxy for standard of living in some contexts. The extent to which
      these associations reflect causality running from economic conditions to height
      cannot be determined from these results.

PMID- 30286525
TI  - A sentinel in Mitraclip intervention: Catch the enemy!
AB  - Cerebral ischemic lesions occurring during transcatheter valve interventions are
      common feared complications and the use of filter device seems to reduce their
      incidence. We report the case of an 84-year old female patient with severe mitral
      regurgitation undergoing MitraClip. During the trans-esophageal echocardiography
      (TEE)-guided procedure was detected the presence of a little fibrin strand
      adherent to the steerable guide catheter for which we decided to implant the
      Claret CE Pro (Claret Medical, Inc. Santa Rosa, CA, USA) cerebral protection
      device and to continue the procedure during which the thrombus disappeared. At
      the end of the procedure a big thrombus was detected in the distal filter. The
      histologic analysis of the debris captured by the filters showed the presence of
      a thrombus, compatible with the image identified by TEE.

PMID- 30286526
TI  - Reaping the Benefits and Avoiding the Risks: Unrealistic Optimism in the Health
      Domain.
AB  - People's perceptions of benefits and risks play a key role in their acceptance or
      rejection of medical interventions, yet these perceptions may be poorly
      calibrated. This online study with N = 373 adults aged 19-76 years focused on
      unrealistic optimism in the health domain. Participants indicated how likely they
      were to experience benefits and risks associated with medical conditions and
      completed objective and subjective numeracy scales. Participants exhibited
      optimistic views about the likelihood of experiencing the benefits and the side
      effects of treatment options described in the scenarios. Objective and subjective
      numeracy were not associated with more accurate ratings. Moreover, participants'
      underestimation of the risks was significantly greater than their overestimation
      of the benefits. From an applied perspective, these results suggest that
      clinicians may need to ensure that patients do not underestimate risks of medical
      interventions, and that they convey realistic expectations about the benefits
      that can be obtained with certain procedures.

PMID- 30286527
TI  - Transradial left gastric artery embolization to treat severe obesity: A pilot
      study.
AB  - BACKGROUND: Bariatric surgery is currently the only effective treatment with long
      lasting results to treat severe obesity. OBJECTIVES: We performed a pilot study
      to evaluate the feasibility, safety and efficacy of percutaneous distal
      embolization of the left gastric artery (LGA) using a transradial approach.
      METHODS AND RESULTS: We recruited seven severely obese male patients (mean age 48
      +/- 7 years) referred for diagnostic coronary angiography. Mean baseline weight
      was 160 +/- 27 kg and body mass index was of 52 +/- 8 kg/m2 . We successfully
      injected 300-500 MUm polyvinyl alcohol particles using 5Fr catheters and all
      distal LGA were occluded at the end of procedures. Mean procedure duration was 24
      +/- 13 min and mean fluoroscopy time was 10 +/- 5 min. Six patients reported mild
      transient epigastric discomfort, which resolved with proton pump inhibitors. At 2
      months, the average weight loss was of 7 +/- 6 kg (median loss: -10 kg [-2, 
      11]), 6 +/- 12 kg (median loss: -9 kg [-16, +4]) at 6 months and 13 +/- 17 kg
      (median loss: -11 kg [0, -25]) up to 12 months after index procedures.
      CONCLUSION: Percutaneous transradial LGA embolization appears to be a promising
      technique to reduce the obesity burden. Randomized trials are required to further
      delineate the risk/benefit ratio, potential clinical indications and long term
      results.

PMID- 30286528
TI  - Analyzing Disaster Loss Trends: A Comparison of Normalization Methodologies in
      South Korea.
AB  - Increasing concern for climate change adaptation and disaster risk reduction is
      driving the need for more accurate and sophisticated tools of analysis to protect
      populations. Standards of analysis that can normalize measurements under various
      contexts are particularly valuable in the global arena of disaster management.
      One concern that may benefit from normalizing is the analysis of disaster loss
      trends. Previous studies have used a combination of inflation, wealth, and
      societal factors in their normalization of disaster loss methodologies. This
      study examines the various normalization methods in previous research and applies
      a selection of eight formulae to 50 years of disaster data in South Korea. The
      results show both decreasing and increasing trends in disaster damage losses
      based on the methods, but there are curious biases under the results that may be
      artifacts of Korea's unique experiences in economic development. The conclusion
      discusses how the case of Korea may help to clarify the optimal normalization
      methodology for other countries.

PMID- 30286529
TI  - Distinctive distributions and migrations of 239+240Pu and 241Am in Chinese
      forest, grassland and desert soils.
AB  - The vertical distributions and downward migrations of the global fallout derived
      239+240Pu and 241Am in diverse types of Chinese soils (forest, grassland and
      desert) were studied. The mean 239+240Pu and 241Am activity concentrations in the
      investigated soil cores were 0.28-0.69 mBq/g and 0.13-0.37 mBq/g, respectively,
      while the accumulative inventories were 61.53-138.99 Bq/m2 for 239+240Pu and
      28.29-61.05 Bq/m2 for 241Am. The convection-dispersion equation (CDE) was used to
      calculate the migration parameters of 239+240Pu and higher apparent dispersion
      coefficients (D) were observed for the acidic forest soils compared with the
      alkaline grassland and desert soils; meanwhile a compartment model was employed
      to compare the migration of 239+240Pu and 241Am in successive soil layers which
      showed that the migration behaviors of 239+240Pu and 241Am were rather similar;
      both velocities were less than 0.3 cm/y in diverse types of soils and these
      findings were compatible with those of short-term laboratory simulation
      experiments in China.

PMID- 30286530
TI  - The characteristics of carbonaceous aerosol in Beijing during a season of
      transition.
AB  - Carbonaceous aerosol was measured during fall of 2010 in Beijing. Daily variation
      of organic carbon (OC) was found to coincide with that of relative humidity (RH),
      and the OC to elemental carbon (EC) ratios were more than doubled during the more
      humid periods (RH above 0.75) compared to other conditions. This large increase
      in OC/EC could not be explained by the variations of primary biomass burning
      emissions but was accompanied by a five-fold increase in the sulfate to EC ratio.
      It was then inferred that secondary organic aerosol (SOA) formation was enhanced
      under the more humid conditions, presumably through aqueous-phase processes. This
      enhanced SOA formation might be partially associated with particles externally
      mixed with black carbon, as indicated by the RH-dependent relationships between
      aerosol optical attenuation and EC loading. In addition, organic aerosols
      exhibited different properties between the more humid and the other periods, such
      that they were less volatile and charred more significantly during thermal
      optical analysis in the former case. These differences coincided with the
      evidence of enhanced SOA formation under the more humid conditions. This study
      highlights the necessity of incorporating aqueous-phase chemistry into air
      quality models for SOA.

PMID- 30286531
TI  - Immobilization and characterization of Fe(0) catalyst on NaOH-treated coal fly
      ash for catalytic reduction of p-nitrophenol.
AB  - In this study, coal fly ash (CFA), i.e., an industrial waste product created in
      large quantities by thermoelectric power plants, was treated with sodium
      hydroxide to afford a novel Fe (0) catalyst supported on alkaline-treated CFA.
      The NaOH-treated CFA (NCFA) exhibited a morphological change from slick spheres
      to pointed, leaf-like spheres, which was accompanied by a noticeable increase in
      specific surface area from 1.2 to 7.5 m2/g. Sequential addition of an Fe(III)
      precursor and NaBH4 solution to a suspension of NCFA resulted in the formation of
      Fe (0) particles on the surface of NCFA (Fe/NCFA). The catalytic activity of
      Fe/NCFA toward the reduction of p-nitrophenol (p-NP) was examined; among the
      Fe/NCFAs synthesized from different NCFAs (1, 3, and 7 M NaOH), the Fe/3 M NCFA
      sample displayed the highest activity owing to the highest Fe content on its
      surface, without leaching any toxic heavy metals. In addition, the effects of
      NaBH4 concentration, Fe loading, and catalyst dosage on the catalytic reduction
      of p-NP by Fe/NCFA were comprehensively investigated. Finally, the recyclability
      and stability of Fe/NCFA were examined, demonstrating the complete reduction of p
      NP over four continuous recycling cycles. The present results demonstrate the
      marked potential of CFA as a component in reactive catalysts for the removal of
      environmental pollutants from wastewater.

PMID- 30286532
TI  - Recovery of phosphorus and nitrogen from human urine by struvite precipitation,
      air stripping and acid scrubbing: A pilot study.
AB  - Sustainable and closed-loop nutrient cycling require the recovery of valuable
      resources from wastewater. Resource recovery from diluted wastewater streams is
      limited by diluted concentrations and unfavorable reaction kinetics. In
      comparison, source separated urine allows resource recovery from a highly
      concentrated nutrient stream, resulting in a more sustainable and efficient
      recovery practice. Different nutrient recovery methods from urine have been
      studied in lab-scale, but pilot or full-scale process evaluations remain sparse.
      In this study, recovery of struvite and ammonium sulfate from urine of pregnant
      women was demonstrated at a pilot-scale treatment facility by means of
      precipitation and air stripping/acid scrubbing. The system achieved 94% struvite
      precipitation efficiency but merely 55% of the crystals were removed and
      recovered. The low phosphorus recovery was due to the washout of small crystals
      that escaped the sieve and settling tank, hence requiring an improved method for
      crystals capture. The removal and recovery efficiencies for nitrogen were 93% and
      85%, respectively. Composition analysis of the produced fertilizers indicated
      that struvite was the dominated precipitate and quality of the ammonium sulfate
      met European standards. Carbamazepine and diclofenac were added in the urine to
      measure the fate of pharmaceuticals in the treatment system. Very little of the
      spiked pharmaceuticals (<0.01%) accumulated in the produced struvite and ammonium
      sulfate. The overall energy demand of the pilot system was 1066 MJ per m3 urine
      processed or 198 MJ per kg N removed. Energy efficiency was not optimized and can
      be improved in many ways.

PMID- 30286533
TI  - Facile one-pot synthesis of a porphyrin-based hydrophilic porous organic polymer
      and application as recyclable absorbent for selective separation of methylene
      blue.
AB  - With the development of dye production and printing industry, dyes wastewater has
      increased dramatically. The resulting environmental pollution problem is
      increasing seriously. In the present work, a porphyrin-based porous organic
      polymer (PPOPs-OH) was synthesized by using pyrrole and 2,6-dihydroxynaphthalene
      1,5-dicarbaldehyde (DHNDA) as basic building block in situ. This method was cost-
      and time-efficient, without the participation of metal catalysts. Further
      reaction of PPOPs-OH with chlorosulfonic acid, a new sulfonic acid functional
      material (PPOPs-SO3H) was obtained with the increasing electronegativity and
      hydrophilicity. PPOPs-SO3H exhibit good adsorption capacity for methylene blue
      (MB) from water (980.4 mg g-1) and excellent selectivity for MB in the present of
      rhodamine B (RhB) and methyl orange (MO). Mechanism investigation revealed that
      electrostatic in comparison with pi-pi interaction is the prominent force in the
      absorption process. Recycling experiments found the absorption properties of
      PPOPs-SO3H did not reduce significantly after several cycles. As a consequence,
      our findings highlight an appealing opportunities for covalent organic polymers
      with their potential application as high-efficiency and robust adsorbents for
      pollutants removal and environmental protection.

PMID- 30286534
TI  - Mass spectrometric identification of in vitro-generated metabolites of two
      emerging organophosphate flame retardants: V6 and BDP.
AB  - The aim of the present study was to investigate the in vitro metabolism of two
      emerging organophosphate flame retardants, namely tetrekis(2
      chlorethyl)dichloroisopentyldiphosphate (V6) and bisphenol-A bis-diphenyl
      phosphate (BDP) in human liver microsomes (HLMs), HLM S9 fractions and in human
      serum. In particular, the role of cytochrome P450 (CYPs) enzymes and/or
      paraoxonases (PONs) in the formation of V6 and BDP phase I metabolites was
      studied. Mono-, di-hydroxylated and hydrolytic phase I metabolites of V6 were
      mainly formed by CYPs in HLMs, while hydrolytic and O-dealkylated phase I
      metabolites of BDP were generated by PONs mainly in serum experiments. Limited
      number of glucuronidated and sulfated phase II metabolites were also identified
      for the two chemicals. The activity of seven recombinant CYPs (rCYPs) including
      rCYP1A2, rCYP2B6, rCYP2C9, rCYP2C19, rCYP2D6, rCYP2E1 and rCYP3A4 in the in vitro
      phase I metabolism of V6 and BDP was investigated. The formation of V6
      metabolites was catalyzed by several enzymes, especially rCYP1A2 that was
      responsible for the exclusive formation of two metabolites, one primary (M1) and
      its secondary metabolite (M9). For BDP, only one phase I metabolite (MM1) was
      catalyzed by the seven rCYPs. Collectively, these results indicate that CYPs have
      a predominant role in the metabolism of V6, while PONs have a predominant role in
      BDP in vitro metabolism. These results are a starting point for future studies
      involving the study of the toxicity, bioaccumulation and in vivo biomonitoring of
      V6 and BDP.

PMID- 30286535
TI  - DnBP-induced thyroid disrupting activities in GH3 cells via integrin alphavbeta3
      and ERK1/2 activation.
AB  - Di-n-butylphthalate (DnBP) exhibits alarming thyroid disrupting activities.
      However, the toxic mechanism of DnBP is not completely understood. In this study,
      we investigated the mechanism of DnBP in thyroid disruption. Rat pituitary tumor
      cell lines (GH3) were treated with DnBP in different scenarios, and cell
      viabilities, target gene transcriptions and protein levels were measured
      accordingly. The results showed that after treatment with DnBP (20 MUmol/L), cell
      proliferation increased to 114.69% (p < 0.01) and c-fos gene was up-regulated by
      1.57-fold (p < 0.01). Both nuclear thyroid hormone receptor beta (TRbeta) and
      membrane TR (integrin alphav and integrin beta3) genes were up-regulated by 1.31
      , 1.08- and 2.39-fold (p < 0.01), respectively, the latter was inhibited by Arg
      Gly-Asp (RGD) peptides; the macromolecular DnBP-BSA was unable to bind nuclear
      TRs, but still promoted cell proliferation to 104.18% and up-regulated c-fos by
      2.99-fold (p < 0.01); after silencing TRbeta gene, cell proliferation (106.64%, p
      < 0.05) and up-regulation of c-fos (1.23-fold, p < 0.01) were also observed. All
      of these findings indicated the existence of non-genomic pathway for DnBP-induced
      thyroid disruption. Finally, DnBP activated the downstream extracellular
      regulated protein kinases (ERK1/2) pathway, up-regulating Mapk1 (1.15-, p <
      0.05), Mapk3 (1.26-fold, p < 0.01) and increasing protein levels of p-ERK (p <
      0.01); notably, DnBP-induced ERK1/2 activation along with c-fos up-regulation
      were attenuated by PD98059 (ERK1/2 inhibitor). Taken together, it could be
      suggested that integrin alphavbeta3 and ERK1/2 pathway play significant roles in
      DnBP-induced thyroid disruption, and this novel mechanism warrants further
      investigation in living organisms.

PMID- 30286536
TI  - Thermo-activated peroxydisulfate oxidation of indomethacin: Kinetics study and
      influences of co-existing substances.
AB  - The widespread occurrence of non-steroidal anti-inflammatory drugs (NSAIDs)
      (e.g., Indomethacin) in the ambient environment has attracted growing concerns
      due to their potential threats to ecosystems and human health. Herein, we
      investigated the degradation of indomethacin (IM) by thermo-activated
      peroxydisulfate (PDS). The pseudo first-order rate constant (kobs) of degradation
      of IM was increased significantly with higher temperatures and PDS doses.
      Moreover, when the initial pH value was raised from 5 to 9 the IM degradation was
      initially decreased and then increased. Basic conditions were favorable for the
      removal of IM in the thermo-activated peroxydisulfate system. A response surface
      methodology based on the Box-Behnken design (BBD) was successfully employed for
      the optimization of the thermo-activated peroxydisulfate (PDS) system. The
      presence of chlorine ions manifested a dual effect on the degradation of IM,
      while bicarbonate and SRFA (as a NOM model) reduced it. Radical scavenging tests
      and electron spin resonance (ESR) revealed that the dominant oxidizing species
      were SO4- and OH at pH 9. Furthermore, the TOC removal efficiency attained 28.8%
      and the release of Cl-was 38.5% at 60  degrees C within 24min, while the
      mineralization rate of IM were 85.5% with the PDS concentration up to 20  mM at 2
      h oxidation. To summarize, thermo-activated PDS oxidation is a promising
      technique for the remediation of IM-contaminated water.

PMID- 30286537
TI  - The role of arbuscular mycorrhiza in mercury and mineral nutrient uptake in
      maize.
AB  - This work aimed to study the role of arbuscular mycorrhizal fungi (AMF) in Hg and
      major mineral nutrient uptake and tissue localization of these elements in the
      roots of maize plants. Maize plants were grown in pots filled with non- and Hg
      contaminated substrate (50 MUg Hg g-1 as HgCl2) and inoculated with two types of
      AMF inocula: a) Glomus sp. originating from Hg-polluted soil of a former Hg
      smelting site in Idrija, Slovenia, and b) commercial AM inoculum Symbivit.
      Controls were inoculated by corresponding bacterial extracts only. Tissue
      localization of Hg and major mineral nutrients was performed by laser ablation
      inductively coupled plasma-mass spectroscopy (LA-ICP-MS) on cryofixed and freeze
      dried root cross-sections. AMF colonization increased plant biomass in non
      contaminated substrate, while this effect was not seen in Hg-contaminated
      substrate. Hg increased total plant biomass more than AMF inoculation, possibly
      through hormetic effects. AMF increased Hg uptake into the roots, as well as Hg
      transfer to the shoots. AMF affected plant mineral nutrient uptake, depending on
      the type of AMF inoculum and the presence of Hg. In the roots, Hg was mainly
      localized in rhizodermis and endodermis, followed by the cortex and the central
      cylinder. Higher Hg concentrations were detected in the central cylinder of AM
      plants than in that of the controls, pointing to a higher Hg mobility and
      potential bioavailability in AMF inoculated plants.

PMID- 30286538
TI  - Toxic responses of zebrafish (Danio rerio) to thallium and deltamethrin
      characterized in the electrocardiogram.
AB  - The electrocardiogram (ECG) has been widely used to objectively address the
      physical condition as an index of stress. Though a numerous accounts of
      investigations on aquatic organisms' ECGs have been made, differentiation of ECG
      parameters in responding to specific toxic chemicals has not been extensively
      studied. In this research, it is hypothesized that zebrafish (Danio rerio) ECG
      parameters would differently respond to different types of pollutants, a heavy
      metal, thallium (Tl, 0.10 and 13.00 MUg/L) and an organic chemical, deltamethrin
      (DM, 0.52 and 2.00 MUg/L). Based on the SOM training and statistical analyses,
      QRS complex could be specified as an indicator of Tl stress, while QT interval
      might be used to evaluate DM stress. Pearson correlation analysis indicated that
      QRS complex and QT interval were significantly associated with Tl stress (r =
      0.854, p = 0.0002) and DM stress (r = 0.792, p = 0.001), respectively. QRS
      complex and QT interval had the highest R2, the minimum of SSE and the lowest AIC
      value in Tl and DM treatments, respectively. Bases on the current experimental
      results and previous reports, QRS complex and QT interval could be considered as
      a specific indicator of Tl and DM disturbances in the environment, respectively.

PMID- 30286539
TI  - Sr isotope fingerprinting of multiple water-source characterizations and its
      environmental implications in a complex lake-groundwater system, Wudalianchi,
      Northeast China.
AB  - The Wudalianchi UNESCO Global Geopark (Northeast China) is famous for its rare
      cold mineral springs and its associated five hydrologically connected barrier
      lakes. During this study, strontium (Sr) isotopes (87Sr/86Sr) were studied along
      with other geochemical data to determine the source of water within the region's
      deep and shallow mineral springs, shallow wells, and lakes. These waters were
      characterized by a relatively narrow range of 87Sr/86Sr ratios (0.70648-0.70816).
      Those ratios were not different in shallow and deep mineral spring waters, and
      probably reflect ratios associated with potassium volcanic rocks in the area as
      expected. When combined with 1/Sr ratios, it appears that the shallow mineral
      springs were derived from upwelling of deep mineral springs and had a composition
      as an endmember of other waters. Shallow mineral springs and wells exhibited
      large variations in Cl-/Sr2+ and NO3-/Sr2+ ratios, owing to the input of
      fertilizers. Farmland runoff and waters from Yaoquan Lake that drains an
      agricultural area also appear to have been influenced by fertilizers and showed
      87Sr/86Sr ratios intermediate between wells and mineral springs. Sewage input is
      likely responsible for this difference and a slight elevation of the ratios in
      the wells. The Wudalianchi lakes had similar variations in 87Sr/86Sr and 1/Sr
      ratios, suggesting their rapid response to terrestrial runoff and the supply of
      shallow mineral springs. Strontium isotope data can be combined with water
      chemistry to emphasize water-rock interaction and refine the region's existing
      model of water interaction in surface and subsurface environments.

PMID- 30286540
TI  - Aqueous removal of inorganic and organic contaminants by graphene-based
      nanoadsorbents: A review.
AB  - Various graphene-based nanoadsorbents, including graphenes, graphene oxides,
      reduced graphene oxides, and their nanocomposites, have been widely studied as
      potential adsorbents due to their unique physicochemical properties, such as
      structural variability, chemical strength, low density, and the possibility of
      large scale fabrication. Adsorption mechanisms are governed largely by the
      physicochemical properties of contaminants, the characteristics of
      nanoadsorbents, and background water quality conditions. This review summarizes
      recent comprehensive studies on the removal of various inorganic (mainly heavy
      metals) and organic contaminants by graphene-based nanoadsorbents, and also
      discusses valuable information for applications of these nanoadsorbents in water
      and wastewater treatment. In particular, the aqueous removal of various
      contaminants was reviewed to (i) summarize the general adsorption capacities of
      various graphene-based nanoadsorbents for the removal of different inorganic and
      organic contaminants, (ii) evaluate the effects of key water quality parameters
      such as pH, temperature, background major ions/ionic strength, and natural
      organic matter on adsorption, (iii) provide a comprehensive discussion of the
      mechanisms that influence adsorption on these nanoadsorbents, and (iv) discuss
      the potential regeneration and reusability of nanoadsorbents. In addition,
      current challenges and future research needs for the removal of contaminants by
      graphene-based nanoadsorbents in water treatment processes are discussed briefly.

PMID- 30286541
TI  - Reconstruction of historical 2,3,7,8-tetrachlorodibenzo-p-dioxin discharges from
      a former pesticide manufacturing plant to the Lower Passaic River.
AB  - Based on chemical fingerprinting and other lines of scientific evidence, a former
      pesticide manufacturing plant in Newark, New Jersey (U.S.A.) has been implicated
      in numerous journal articles as the major source of 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) in the sediments of the Lower Passaic River (LPR). Although the
      site has been extensively studied for over three decades, no previous study has
      identified a pathway capable of discharging an amount of 2,3,7,8-TCDD comparable
      to the mass estimates made for 2,3,7,8-TCDD in the sediments of the LPR and
      Newark Bay, or examined the timing of specific manufacturing processes at the
      site in relation to 2,3,7,8-TCDD concentrations in dated sediment cores. A
      reconstruction of the historical operations at this site was performed,
      supporting it as the major source of 2,3,7,8-TCDD to the LPR. A 2,4,5
      trichlorophenol purification process, utilized prior to September 1954, was
      specifically identified as a significant source of 2,3,7,8-TCDD to the LPR. This
      purification process generated a dioxin-rich sludge that was discharged to the
      river prior to September 1954. Annual 2,4,5-trichlorophenol production, coupled
      with modeling to predict concentrations of 2,3,7,8-TCDD, indicate that 2,3,7,8
      TCDD discharges to the LPR from this one process (20-80 kg) are consistent with
      mass estimates of 2,3,7,8-TCDD in the river (30-50 kg). 2,3,7,8-TCDD and cesium
      137 data from nearby sediment cores support this purification process as a major
      pathway by which 2,3,7,8-TCDD entered the river.

PMID- 30286542
TI  - Studies on the influence of sampling on the levels of dioxins and PCB in fish.
AB  - Beaked redfish (Sebastes mentella) and Greenland halibut (Reinhardtius
      hippoglossoides) were collected in waters around Svalbard (Barents Sea) to study
      the influence of different muscle separation/filleting techniques at small and
      medium fishes on the dioxin/PCB content. Sampling of both species included
      preparation techniques such as fillets with or without belly flaps, commercially
      trimmed fillets and cutting into anterior and posterior cutlets. In case of
      Greenland halibut also the whole edible muscle part and middle cutlets were
      studied. All samples analysed were far below the maximum level of 6.5 pg/g wet
      weight (ww) WHO-PCDD/F-PCB-TEQ and 75 ng/g ww ndl-PCB. Trimmed fillets of beaked
      redfish had the lowest fat content and the lowest level of dioxins and PCB
      (1.70%, WHO-PCDD/F-PCB-TEQ = 0.320 pg/g ww). The respective posterior cutlets
      showed the highest fat content and highest levels of dioxins and PCB (2.66%, WHO
      PCDD/F-PCB-TEQ = 0.729 pg/g ww). Levels of dioxins and PCB in Greenland halibut
      samples were generally higher and ranged between WHO-PCDD/F-PCB-TEQ = 0.784 pg/g
      ww (fillets without bells flaps, fat content = 8.83%) and WHO-PCDD/F-PCB-TEQ =
      2.022 pg/g ww (edible part whole muscle, fat content = 8.62%). The results show a
      considerable influence of the different sampling methods on the dioxin and PCB
      levels of the species analysed.

PMID- 30286544
TI  - Adsorption removal of anionic dyes from aqueous solutions by chitosan
      nanoparticles deposited on the fibrous carrier.
AB  - The synthesis, characterization and environmental application of chitosan based
      material stable in acidic media for adsorption of anionic dyes were investigated.
      The adsorption material is chitosan nanoparticles immobilized on a fibrous
      carrier (CPF). The choice of optimal conditions for the preparation of chitosan
      particles and their immobilization on a chemically activated polyethylene
      terephthalate (PET) fiber is justified. Immobilized nanoparticles showed high
      adsorption rates and dye binding capacity (300-1050 mg g-1) depending on the dye
      type. Anionic phthalocyanine dyes having different molecular sizes, different
      nature and number of anionic groups were used as model adsorbates. The
      experimental isotherm data and a linear correlation coefficients (rL2 > 0.99)
      have shown that the dyes adsorption on CPF is best predicted by the Langmuir
      isotherm. The adsorption rate has been found to conform to pseudo-second-order
      kinetics with a good correlation (R2 > 0.99) with intra-particle diffusion as one
      of the rate determining steps. It has been is established that the sorption rate
      and the limiting sorption capacity decrease with the increment in the dye
      molecule size. The process of adsorption of the dyes on the CPF is pH-insensitive
      in the pH range of 2-8. The adsorption saturated CPF could be effectively
      regenerated by a simple alkaline washing.

PMID- 30286543
TI  - Occurrence, removal and risk assessment of steroid hormones in two wastewater
      stabilization pond systems in Morogoro, Tanzania.
AB  - The present study investigated the occurrence and removal of 10 steroid hormones
      (4 androgens, 3 progestagens and 3 estrogens) in two WSP systems, Mafisa and
      Mzumbe in Morogoro, Tanzania. All 10 steroid hormones were detected in the
      influent of both WSP systems in the dry as well as in the rainy season. The
      concentrations of steroids in influent wastewater ranged from 0.1 ng/L for 17-OH
      pregnenolone to 445 ng/L for estrone and from below limit of detection for 17-OH
      pregnenolone to 45 ng/L for estrone in effluent. During dry season, the overall
      mean +/- standard deviation removal efficiency for the 10 steroids were 70 +/-
      21% for Mzumbe WSP and 97 +/- 3% for Mafisa WSP. During the rainy season the
      overall mean removal efficiency for all the steroid hormones were 52 +/- 32% for
      Mzumbe WSP and 94 +/- 8% for Mafisa WSP. Risk was characterized by calculating
      the risk quotients (RQs) for fish and humans. 46% of the total RQs calculated
      were above one, indicating high risk. Low RQs were estimated for androgens and
      progestagens but the estrogen concentrations measured in the WSP systems and
      Morogoro River indicated a high risk for fish. However, estrogens appeared not to
      pose an appreciable risk to human health from water intake and fish consumption.
      The results indicated that WSP systems are quite effective in removing steroid
      hormones from wastewater. Thus, low technology systems such as WSP systems are
      suitable techniques in low income counties due to relatively low costs of
      building, operating and maintaining these systems.

PMID- 30286545
TI  - Spatiotemporal variation and potential risks of seven heavy metals in seawater,
      sediment, and seafood in Xiangshan Bay, China (2011-2016).
AB  - The residues and risks of heavy metals in the environment and organisms have
      attracted great concern for many years. However, the information on their long
      term spatiotemporal trends and potential health and ecological risks are scarce.
      In this study, a total of 1815 seawater samples, 451 sediment samples, and 54
      seafood samples were collected in Xiangshan Bay, China, between 2011 and 2016.
      The residue, distribution, seasonal variation, and potential health risks of
      seven heavy metals in seawater, sediment, and seafood were evaluated. Dissolved
      Zn (mean = 16.8 MUg L-1) and Cu (mean = 3.4 MUg L-1) concentrations were high in
      seawater. Sediments were mainly contaminated by Zn (mean = 120.8 mg kg-1) and Cr
      (mean = 81.7 mg kg-1). The highest levels of Cu and Zn were observed in Ostreidae
      with the concentrations of 84.3 and 99.0 mg kg-1, respectively. The Kendall test
      indicated that only As, Cu, Cd, and Hg showed decreasing trends in seawater with
      time and no significant temporal trends were identified for heavy metals in
      sediment between 2011 and 2016. Only As may pose non-carcinogenic risks to both
      adults and children in some seafood. These data provide a reliable reference for
      government to use in developing reasonable and scientific regulations on the
      ecological and food safety of this area.

PMID- 30286546
TI  - Investigation of reactive oxygen species produced by microwave electrodeless
      discharge lamp on oxidation of dimethyl sulfide.
AB  - Microwave electrodeless discharge lamp (MEDL) has been regarded as a powerful
      light source of photoreaction. Four kinds of chemicals, nitrogen (N2), oxygen
      (O2), water (H2O) and dimethyl sulfide (DMS), were used as molecular probes to
      explore the generation process of reactive oxygen species (ROS) and their photo
      oxidation performances on the photodegradation of organic pollutants with
      application of an exterior MEDL system. ROS such as O (3P), O3, O (1D) and 1O2
      were generated via irradiation of O2 and H2O except dry N2 by MEDL. They were
      transformed to other ROS including .OH and H2O2 with increase of relative
      humidity. The ROS productivity was inhibited evidently by humidity and .OH became
      the major active species at high humidity. An optimal mineralization rate of
      23.6% for DMS photodegradation was reached in dry air compared with 8.74% at high
      humidity, which indicated that O (1D) and 1O2 were more powerful oxidants than O3
      and OH. The results showed that the higher mineralization rate of organic
      pollutants was obtained by increasing the generation efficiency of ROS of O (1D)
      and 1O2. Furthermore, the results provided an alternative to develop
      intensification technology on photodegadation of organic pollutants with MEDL
      system and an optimal operation process including photocatalyst and humidity.

PMID- 30286547
TI  - On-site treatment of flowback and produced water from shale gas hydraulic
      fracturing: A review and economic evaluation.
AB  - On-site flowback treatment systems are typically rated and selected based on
      three fundamental categories: satisfying customer needs (e.g. meeting effluent
      quality, capacity, delivery time and time required to reach stable and steady
      effluent quality), common features comparison (e.g. treatment costs, stability of
      operation, scalability, logistics, and maintenance frequency) and through
      substantial product differentiation such as better service condition, overcoming
      current market limitations (e.g. fouling, salinity limit), and having lower
      environmental footprints and emissions. For treatment of flowback, multiple on
      site treatment systems are available for primary separation (i.e. reducing TSS
      concentrations and particle size below 25 MUm for disposal), secondary separation
      (i.e. removing TSS, iron and main scaling ions, and reducing particle size up to
      5 MUm for reuse), or tertiary treatment (i.e. reducing TDS concentration in the
      permeate/distillate to below 500 mg/L) for recycling or discharge. Depending on
      geographic features, frac-fluid characteristics, and regulatory aspects,
      operators may choose disposal or reuse of flowback water. Among these approaches,
      desalination is the least utilized option while in the majority of cases on-site
      basic separation is selected which can result in savings up to $306,800 per well.
      Compared to desalination systems, basic separation systems (e.g.
      electrocoagulation, dissolved air floatation) have higher treatment capacity (159
      4133 m3/d) and specific water treatment production per occupied space (8.9-58.8
      m3/m2), lower treatment costs ($2.90 to $13.30 per m3) and energy demand, and
      finally generate less waste owing to their high recovery of 98-99.5%, which
      reduces both operator costs and environmental burdens.

PMID- 30286548
TI  - Integrative analysis of methylome and transcriptome variation of identified
      cardiac disease-specific genes in human cardiomyocytes after PM2.5 exposure.
AB  - PM2.5 exposure is strongly linked to cardiac disease. Subtle epigenetic or
      transcriptional alterations induced by PM2.5 might contribute to pathogenesis and
      disease susceptibility of cardiac disease. It is still a major challenge to
      identify biological targets in human genetics. Human cardiomyocytes AC16 was
      chosen as cell model. Epigenetic effect of PM2.5 in AC16 was analyzed using
      Illumina HumanMethylation 450 K BeadChip. Meanwhile the transcriptomic profiling
      was performed by Affymetrix(r) microarray. PM2.5 induced genome wide variation of
      DNA methylation pattern, including differentially methylated CpGs in promoter
      region. Then gene ontology analysis demonstrated differentially methylated genes
      were significantly clustered in pathways in regulation of apoptotic process, cell
      death and metabolic pathways, or associated with ion binding and shuttling.
      Correlation of the methylome and transcriptome revealed a clear bias toward
      transcriptional suppression by hypermethylation or activation by hypomethylation.
      Identified 386 genes which exhibited both differential methylation and expression
      were functionally associated with pathways including cardiovascular system
      development, regulation of blood vessel size, vasculature development, p53
      pathway, AC-modulating/inhibiting GPCRs pathway and cellular response to metal
      ion/inorganic substance. Disease ontology demonstrated their prominent role in
      cardiac diseases and identified 14 cardiac-specific genes (ANK2, AQP1 et al.).
      PPI network analysis revealed 6 novel genes (POLR2I, LEP, BRIX1, ADCY6, INSL3,
      RARS). Those genes were then verified by qRT-PCR. Thus, in AC16, PM2.5 alters the
      methylome and transcriptome of genes might be relevant for PM2.5-/heart
      associated diseases. Result gives additional insight in PM2.5 relative cardiac
      diseases/associated genes and the potential mechanisms that contribute to PM2.5
      related cardiac disease.

PMID- 30286549
TI  - Arsenic exposure, profiles of urinary arsenic species, and polymorphism effects
      of glutathione-s-transferase and metallothioneins.
AB  - This study assessed the effects of polymorphic variants of gutathione-S
      transferase and metallothioneins on profiles of urinary arsenic species. Drinking
      groundwater from Margarita and San Fernando, Colombia were analyzed and the
      lifetime average daily dose (LADD) of arsenic was determined. Specific surveys
      were applied to collect demographic information and other exposure factors. In
      addition, GSTT1-null, GSTM1-null, GSTP1-rs1695 and MT-2A-rs28366003 genetic
      polymorphisms were evaluated, either by direct PCR or PCR-RFLP. Urinary speciated
      arsenic concentrations were determined by HPLC-HG-AFS for species such as AsIII,
      AsV, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and total urinary
      As (TuAs). Primary methylation index (PMI) and secondary methylation index (SMI)
      were also calculated as indicators of the metabolic capacity. Polymorphisms
      effects were tested using multivariate analysis, adjusted by potential
      confounders. The As concentrations in groundwater were on average 34.6 +/- 24.7
      MUg/L greater than the WHO guideline for As (10 MUg/L). There was a correlation
      between As concentrations in groundwater and TuAs (r = 0.59; p = 0.000). Urinary
      inorganic arsenic (%InAs) was associated with GSTP1, LADD, GSTP1*Age,
      GSTP1*alcohol consumption (r2 = 0.43; likelihood-ratio test, p = 0.000). PMI was
      associated with sex (r2 = 0.20; likelihood-ratio test, p = 0.007). GSTP1 (AG +
      GG) homozygotes/heterozygotes could increase urinary %InAs and decrease the PMI
      ratio in people exposed to low and high As from drinking groundwater. Therefore,
      the explanatory models showed the participation of some covariates that could
      influence the effects of the polymorphisms on these exposure biomarkers to As.

PMID- 30286550
TI  - Induced-fit adsorption of diol-based porous organic polymers for tetracycline
      removal.
AB  - Adsorption is recognized as one of the most efficient approaches for antibiotics
      removal from water. Inspired by the enzyme-substrate interaction model, we
      proposed induced-fit adsorption (IFA) model, and rationally designed and
      fabricated diol-based porous organic polymers (POPs) as adsorbents for
      tetracycline (TC) removal. For 2,3-naphthalenediol-based POP (NTdiol-POP), the
      preferable geometry of diol-groups contributed to the high binding energy with TC
      species and flexible methylene linkages between neighboring rigid naphthalene
      rings gave rise to precisely matching between TC species and adsorbents, that is,
      the induced-fit conformation change. As a result, NTdiol-POP exhibited a high
      saturated adsorption capacity of 155.8 mg g-1. More importantly, NTdiol-POP
      exhibited excellent TC removal efficiencies in both concentrated solution (96%
      for 4 p.p.m) and trace level solution (97% for 250 p.p.b).

PMID- 30286551
TI  - Debromination of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) by synthetic Pd/Fe0
      and Cu/Fe0 in different protic solvents.
AB  - Polybrominated diphenyl ethers (PBDEs) belong to a class of persistent organic
      pollutants (POPs), with potential toxicity to the liver, reproductive system, and
      development of mammals. The highly toxic and concentrated congener, 2,2',4,4'
      tetrabromodiphenyl ether (BDE-47), was chosen to investigate debromination
      mechanisms by the two synthetic iron-based bimetals (Pd/Fe0 and Cu/Fe0) in two
      protic solvents (water and ethanol). SEM, XPS, and BET analyses showed that the
      synthetic bimetals Pd/Fe0 and Cu/Fe0 were spherical with diameters of about 100
      nm and loaded with ~1% (wt%) of Pd and Cu, respectively. GC-MS was used for the
      analysis of degradation products and the chromatograms showed that both Pd/Fe0
      and Cu/Fe0 bimetals had effective reducing properties in water solvent. In
      ethanol solvent, debromination of BDE-47 by Pd/Fe0 showed a similar high
      activity, but BDE-47 could be hardly degraded by Cu/Fe0. The dominant
      debromination products of BDE-47 by Pd/Fe0 and Cu/Fe0 were ortho-substituted and
      para-substituted BDEs, respectively. Active H-atomic transfer was found to play a
      key role in the debromination of BDE-47 by Pd/Fe0 in both, water and ethanol,
      with a preference for para-debromination along with the formation of dibenzo-p
      furan (DF) as the by-product, mainly in water. In contrast, electron transfer
      with a preference for ortho-debromination was found to play a predominant role
      for Cu/Fe0 system in water. More importance should be provided to active H-atomic
      transfer for its high efficiency. In-depth study on the mechanism of formation of
      by-product DF would be significant for its higher toxicity, possibility of
      accumulation and migration in the environment.

PMID- 30286552
TI  - Sulfur autotrophic denitrification (SAD) driven by homogeneous composite
      particles containing CaCO3-type kitchen waste for groundwater remediation.
AB  - This study first developed homogeneous sulfur/buffer composite particles to
      obtain an alkalinity-uniform and cost-effective sulfur autotrophic
      denitrification (SAD) technology. As single solid-phase material, the composites
      performed better in enrichment of microorganisms and stabilization of S/C ratio
      throughout the reaction. Natural CaCO3-type kitchen waste, used as a buffer in
      the developed composites, was conducive to providing rich metal nutrients (K, Na,
      Mg, Al, and Ca) for the metabolism of microorganisms. Maximum denitrification
      efficiency of 96.4%, 96.8% and 96.8% were obtained by the 1.25:1 PSL, 1.72:1 PSE
      and 1.25:1 PSS composites, respectively, and nitrate removal rates of >0.6 mg-N/L
      h and stable pH between 6.20 and 8.00 were achieved. The S0-eggshell microcosms
      showed more significant accumulations of ammonium-N and sulfate, reaching ~1.2 mg
      N/L and 405.99 +/- 9.47 mg/L, respectively. When dealing with nitrate in real
      groundwater, the composites showed a great advantage over the dispersed materials
      at a denitrification efficiency of more than 99.7% and rate of 0.40 mg-N/L-h. No
      ammonium was observed by PSE and PSS throughout the batch. This study confirmed
      the potential of waste composites to enhance SAD performance in nitrate
      contaminated groundwater remediation.

PMID- 30286553
TI  - Multi-scale analysis of heavy metals sources in soils of Jiangsu Coast, Eastern
      China.
AB  - Since the development of Jiangsu Coast was proposed as a national strategy by the
      Chinese Government in 2009, Jiangsu Coast has been experiencing rapid and
      intensive development in industry and tidal flat reclamation, which has
      inevitably led to the accumulation of heavy metals in its soils. A total of 239
      samples (0-20 cm) were collected from topsoils of Jiangsu Coast, and their
      concentrations of Cd, Cr, Cu, Hg, Ni, Pb, and Zn were determined. Factorial
      kriging was applied to examine the scale-dependent correlations between heavy
      metals and to generate the spatial components at multiple scales, and
      multivariate stepwise regression was used to explore the relationships between
      the spatial multi-scale components of heavy metals and environmental factors.
      Linear model of co-regionalization (LMC) fitting indicated that the multi-scale
      variation comprised a nugget effect, an exponential structure with a range of 15
      km (local scale), and a spherical structure with a range of 135 km (regional
      scale). The spatial correlations of seven heavy metals depended on their spatial
      scales, and their correlations increased with the increasing scales. Spatial
      variations in Cr and Ni were associated with natural geochemical sources on both
      local and regional scales. Parent material influenced the basic spatial
      variations in Cd, Cu, Pb and Zn on both local and regional scales, but human
      activity also contributed to the spatial variations in these four metals. The
      human inputs of Cd, Cu, Pb, and Zn differed on these two scales. Hg was dominated
      by industrial emissions and agricultural practices on both scales.

PMID- 30286554
TI  - Atrazine induced oxidative stress and mitochondrial dysfunction in quail
      (Coturnix C. coturnix) kidney via modulating Nrf2 signaling pathway.
AB  - Atrazine (ATR) is a most used herbicide which is believed as a pivotal
      determinant of environmental nephrosis, but potential mechanism is still largely
      unclear. This study intends to reveal a novel mechanism of ATR-induced
      nephrotoxicity. Quail were treated with 0, 50, 250 and 500 mg ATR/kg/d by oral
      gavage for 45 days. Kidney coefficient was decreased, biochemical and morphologic
      indices reflecting the kidney injury were significantly increased in ATR-exposed
      quail. ATR exposure upregulated the expression of proapoptotic factors (Bax,
      Caspase 3 and FasL) and downregulated antiapoptotic factor (Bcl-2). Notably,
      cristae of mitochondria decreased, mitochondrial malformation and mitochondrial
      vacuolar degeneration were observed in ATR-exposed quail. ATR induced the
      disorder of mitochondrial function related factors expressions and promoted
      oxidative damage. Furthermore, ATR induced toxicities in the expression of Nrf2
      and Nrf2-target genes. In conclusion, ATR altered the microstructure and function
      of quail kidney. ATR induced renal damage via causing mitochondrial dysfunction,
      influencing mitochondrial function related genes expression, modulating Nrf2
      signaling pathway. This study suggested ATR induced the nephrotoxicity via
      disturbing the transcription of mitochondrial function related factors and Nrf2
      signaling pathway.

PMID- 30286555
TI  - Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans associated
      with settling particles in Lake Ontario.
AB  - Sediment traps were deployed at seven sites in the western and central basins of
      Lake Ontario for calculation of concentrations and down fluxes for
      polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) to assess
      ongoing loadings to Lake Ontario from the Niagara River watershed. Traps were
      deployed at multiple depths (beginning at 20 m) during two seasonal time periods
      at stations impacted by the outflow of the Niagara River, and stations reflecting
      deeper water offshore conditions. Settling particles were collected seasonally to
      assess the influence of physical characteristics of the water column, i.e.,
      isothermal conditions vs. stratified conditions, on concentrations and fluxes of
      PCDD/Fs. At all stations and for all depth intervals, PCDD/F concentrations were
      higher in the winter sampling period (range of 3120-10,600 pg g-1), compared to
      the spring - summer - fall time period (range of 320-6900 pg g-1). These results
      indicated bottom sediments in central and western Lake Ontario were more highly
      contaminated, compared to contemporary particulate material entering the lake via
      the Niagara River or resulting from shoreline erosion. However, assessment of
      PCDD/F congener profiles and ratios also indicated source areas within the
      Niagara River watershed continued to episodically contribute loadings to Lake
      Ontario. The results also indicated changes in discharges of PCDD/Fs from sources
      in the Niagara River result in changes in congener profiles in settling
      particles, which can be detected by continued monitoring.

PMID- 30286557
TI  - Anesthesiologist, Anaesthetist, Anesthetist, Et Cetera: A Summary of English
      Names for Anesthesia Professionals in Several Regions.

PMID- 30286556
TI  - Characterization and imaging of lead distribution in bones of lead-exposed birds
      by ICP-MS and LA-ICP-MS.
AB  - Lead (Pb) poisoning in raptors and water birds is a serious problem in many
      countries. However, only a small fraction of Pb poisoning has been detected in
      birds. Bone specimens may be useful indices of Pb exposure because bones contain
      ~90% of the total Pb body burden. The original purpose of this study was to
      comprehensively analyze Pb accumulation in various bone types using inductively
      coupled plasma-mass spectrometry (ICP-MS). Since our results showed that Pb
      accumulation differed greatly depending on bone type, a secondary objective was
      defined, aiming to investigate the fine Pb distribution and its relation to bone
      structure and bone marrow by using laser ablation (LA)-ICP-MS. Our findings
      suggested that bone samples (1) consisting of trabecular tissue and (2) those
      that contain bone marrow could accumulate high levels of Pb following acute
      exposure. The shorter turnover time of trabecular bone can cause a rapid
      accumulation of Pb, and bone marrow may have an important role for internal
      exposure of Pb to bone tissue. Pb is accumulated in bones via blood flow, and
      bone marrow receives blood from outside the bones. In conclusion, bone samples
      provide valuable information on Pb exposure and could be useful to investigate
      and understand mortalities related to suspected Pb poisoning.

PMID- 30286558
TI  - The Beneficial Effects of alpha-Lipoic Acid in Critically Ill Patients: A
      Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.
AB  - BACKGROUND: Critical illness is associated with oxidative stress and insulin
      resistance. These conditions affect the clinical outcomes in intensive care unit
      (ICU). The aim of this study was to determine whether intervention with alpha
      lipoic acid (ALA) influences the oxidative stress, insulin resistance, and
      clinical outcomes in critically ill patients. METHOD: In this randomized double
      blind placebo-controlled trial, 80 critically ill patients who were expected to
      stay at least seven days in the ICU and required enteral feeding were randomly
      allocated to two equal groups to receive either ALA (900 mg) or placebo daily for
      10 days. Serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA),
      insulin, glucose (GLC), C-reactive protein (CRP), albumin (Alb), prealbumin
      (preAlb), total protein (total-pr) and total lymphocyte count (TLC) as well as
      homeostasis model assessment-estimated insulin resistance (HOMA-IR) were measured
      at baseline and at the end of ALA supplement phase. Clinical outcomes (length of
      ICU/hospital stay, ICU/hospital mortality, and 28-day mortality and ventilator
      free days) were also recorded. RESULTS: TAC increased significantly in the ALA
      supplemented group compared to the placebo group (p < 0.001). Moreover, serum
      levels of GLC decreased significantly in the ALA group compared to lack of
      changes in the placebo group (p = 0.011). ALA supplementation also hindered an
      increase in HOMA-IR (p = 0.015). There were no significant differences in other
      biochemical markers and clinical outcomes between the two groups. CONCLUSION: ALA
      may be an effective supplement to improve antioxidant defense and insulin
      resistance in critically ill patients.

PMID- 30286559
TI  - Enhanced Perioperative Safety and Comfort During Airway-Related Surgeries and
      Procedures With Dexmedetomidine-A Brief Review and Clinical Practice Experience.
AB  - Dexmedetomidine, an alpha-2 adrenergic receptor agonist, provides analgesia,
      sedation, anxiolysis, sympatholysis and anesthetic-sparing effect, without
      inducing significant respiratory depression. Due to these properties, its
      clinical use is no longer limited to serving as a sedative agent in the intensive
      care unit. Proper airway management and the avoidance of cardiac and respiratory
      complications are common goals of everyday anesthesia practice. Ensuring airway
      safety is pivotal during the anesthesia stages of induction, maintenance and
      recovery. In this review, we focus on the advantages of dexmedetomidine in awake
      fiberoptic intubation (AFOI), diagnostic examinations and surgeries of patients
      with obstructed airways, and reducing emergence delirium effectively without
      causing further adverse events. With increasing implementation in different
      anesthetic scenarios, dexmedetomidine provides a favorable option to enhance
      patient safety and comfort.

PMID- 30286560
TI  - Considerations for One-Lung Ventilation in Patients With Right Main Bronchus
      Abnormalities.

PMID- 30286561
TI  - Delayed Malposition of Central Venous Catheter Induced Mediastinum Hematoma With
      Innominate Vein Perforation.
AB  - Central venous catheterization (CVC) is a common invasive procedure. Although it
      is a relatively safe procedure, severe complications occurred sometimes. One of
      the most serious complications is large vessel perforation. A 40-year-old man was
      send to intensive care unit (ICU) after liver transplantation surgery with
      massive blood transfusion. Four days later, chest computed tomography (CT) were
      arranged for unknown leukocytosis and high level of procalcitonin. Chest CT
      revealed possibility of innominate vein perforation by CVC. Surgeon confirmed the
      malposition of CVC complicated perforation and repaired innominate vein.
      Unfortunately, the patient passed away 8 days later after this re-operation even
      initially better condition after aggressive treatment. Delayed malposition of CVC
      is a rare cause for CVC complications. To minimize incidence of this severe
      complication, catheterization should be performed very carefully and post
      procedure position checking is indicated.

PMID- 30286562
TI  - Primary Rhabdomyosarcoma of the Breast: A Report of Two Cases and Literature
      Review.
AB  - Primary rhabdomyosarcoma (RMS) of the breast is very rare, which often leads to
      delayed histologic confirmation. Here, we report two cases of primary RMS of the
      breast: spindle cell/sclerosing (ssRMS) and alveolar (aRMS). These two primary
      RMS patients were teenage girls who underwent mastectomy. The patient with ssRMS
      experienced recurrence at the operative site four months after surgery despite
      concurrent chemoradiation therapy. The aRMS patient had multiple metastatic
      lesions at the time of diagnosis and an association with FAX3-FOXO1 (FKHR) fusion
      transcripts; she died 22 months post-diagnosis. This is the second report of
      primary ssRMS of the breast. We also reviewed all published literature concerning
      primary RMS of the breast.

PMID- 30286563
TI  - The Expression of Adipophilin Is Frequently Found in Solid Subtype Adenocarcinoma
      and Is Associated with Adverse Outcomes in Lung Adenocarcinoma.
AB  - BACKGROUND: The up-regulation of the lipogenic pathway has been reported in many
      types of malignant tumors. However, its pathogenic role or clinical significance
      is not fully understood. The objective of this study was to examine the
      expression levels of adipophilin and related hypoxic signaling proteins and to
      determine their prognostic impacts and associations with the pathologic
      characteristics of lung adenocarcinoma. METHODS: Expression levels of
      adipophilin, heat shock protein 27 (HSP27), carbonic anhydrase IX, and hypoxia
      inducible factor 1alpha were examined by immunohistochemical staining using
      tissue microarray blocks. Correlations between protein expression levels and
      various clinicopathologic features were analyzed. RESULTS: A total of 230 cases
      of primary adenocarcinoma of the lung were enrolled in this study. Adipophilin
      expression was more frequent in males and with the solid histologic type. It was
      correlated with HSP27 expression. Patients with adipophilin-positive
      adenocarcinoma showed a shorter progression-free survival (PFS) (median PFS, 17.2
      months vs 18.4 months) in a univariable survival analysis, whereas HSP27
      positivity correlated with favorable overall survival (OS) and PFS. In a
      multivariable analysis, adipophilin and HSP27 were independent prognostic markers
      of both OS and PFS. CONCLUSIONS: Activated lipid metabolism and the hypoxic
      signaling pathway might play a major role in the progression of lung
      adenocarcinoma, especially in the solid histologic type.

PMID- 30286564
TI  - Case Series Review of the Safety and Efficacy of Endoscopic Ultrasound-Guided
      Splenic Mass Core Biopsy.

PMID- 30286565
TI  - Clinical characteristics in Japanese children with nonobese type 2 diabetes.
AB  - It is well known that the incidence of youth-onset type 2 diabetes is increasing
      worldwide. On the other hand, most studies have shown that the majority of youth
      onset type 2 diabetes occurs in obese individuals, generally with a body mass
      index (BMI) greater than the 90th or 95th centile for sex- and age-matched
      children and adolescents. However, we identified some Japanese children with
      nonobese type 2 diabetes and BMI less than 90th centile by a urine glucose
      screening program at schools in the Tokyo Metropolitan Area. According to the
      results obtained from the screening, clinical characteristics of patients with
      nonobese type 2 diabetes seemed to be different from those in obese type 2
      diabetes. Nonobese patients tended to show lower insulin secretion abilities and
      milder, but evident, insulin resistance from the time of diagnosis. Female, low
      birth weight (small for gestational age), and genetic background, not related to
      beta-cell-associated autoimmunity, may play a role in development of nonobese
      type 2 diabetes. In addition, nonobese patients tend to progress earlier to
      pharmacological treatment including oral hypoglycemic drugs and insulin. Further
      studies are needed to confirm to these findings and clarify the pathophysiology
      of children with nonobese type 2 diabetes.

PMID- 30286566
TI  - Type 2 diabetes mellitus in children and adolescent: an Indonesian perspective.
AB  - The prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents has
      increased globally over the past 2 decades. Metabolic syndrome, including obesity
      and overweight at a young age, increases the occurrence of T2DM. Studies in
      Indonesia have found that obese children and adolescents are more likely to have
      insulin resistance, a risk factor for T2DM. There are no data on the current
      incidence of T2DM in youth in Indonesia, but there has been a significant rise in
      the prevalence of overweight in adolescents. The diagnosis of T2DM in youth is
      similar to that in adults, with special consideration of when to test
      asymptomatic children. Management of T2DM in Indonesia follows the
      recommendations of the Indonesian Pediatric Society, which include lifestyle
      modifications, such as improving dietary habits and exercise, as well as
      appropriate medications. Metformin is the drug of choice for young T2DM patients;
      if marked hyperglycemia is present, basal insulin is given with metformin.
      Monitoring of T2DM is generally done through selfmonitoring of blood glucose and
      glycosylated hemoglobin.

PMID- 30286567
TI  - Childhood diabetes in India.
AB  - This review describes the epidemiology of childhood diabetes in India. It focuses
      on the incidence and prevalence of type 1 diabetes and its complications and
      comorbid conditions. The review also covers data related to type 2 diabetes,
      glucose intolerance, and monogenic diabetes from India. A brief discussion
      regarding unique contributions from India to the world literature is included.
      The topics discussed include use of camel milk as adjuvant therapy in type 1
      diabetes, relevance of the A1/A2 hypothesis, and comprehensive clinico
      etiopathological classification of type 1 diabetes.

PMID- 30286568
TI  - Therapeutic potential of alpha-1 antitrypsin in human disease.
AB  - Alpha-1 antitrypsin (AAT), an alpha globulin glycoprotein, is a member of the
      serine protease inhibitor (serpin) superfamily. The clinical significance of AAT
      is highlighted by AAT deficiency. Genetic deficiency of AAT can present as
      several neutrophilic diseases associated with emphysema, liver cirrhosis,
      panniculitis, and systemic vasculitis. Recently, animal and human studies have
      shown that AAT can control inflammatory, immunological, and tissue-protective
      responses. In addition, AAT treatment can prevent overt hyperglycemia, increase
      insulin secretion, and reduce cytokine-mediated apoptosis of pancreatic beta
      cells in diabetes. These multifunctional roles of AAT draw attention to the
      glycoprotein's therapeutic potential for many inflammatory and autoimmune
      diseases beyond AAT deficiency. As underlying mechanisms, recent studies have
      suggested the importance of serine protease inhibitory activity of AAT in obesity
      associated insulin resistance, chronic obstructive pulmonary disease, and cystic
      fibrosis. In this review, we explore the multiple functions of AAT, in
      particular, the anti-inflammatory and serine protease inhibitory functions, and
      AAT's therapeutic potential in a variety of human diseases through published
      literature.

PMID- 30286569
TI  - Evaluation of bone mineral status in prepuberal children with newly diagnosed
      type 1 diabetes.
AB  - PURPOSE: Many studies have reported that patients with type 1 diabetes have
      reduced bone mineral density (BMD). We assessed bone status in prepubertal
      children with type 1 diabetes mellitus (type 1 DM) at initial diagnosis and
      investigated factors associated with BMD. METHODS: Prepubertal children (n=29)
      with newly diagnosed type 1 diabetes from 2006 to 2014 were included. Dual-energy
      X-ray absorptiometry measured regional and whole-body composition at initial
      diagnosis. BMD was compared with healthy controls matched for age, sex, and body
      mass index (BMI). RESULTS: The mean age of all subjects (16 boys and 13 girls)
      was 7.58+/-1.36 years (range, 4.8-11.3 years). Initial mean glycosylated
      hemoglobin (HbA1c) level was 12.2%+/-1.9%. The mean BMD z-scores of lumbar spine,
      femur neck, and total body were not significantly different between patients and
      controls. Three patients (10.3%) had low bone density (total body BMD standard
      deviation score [SDS] < -2.0). To identify determinants of lumbar spine BMD z
      score, multivariate regression analysis was performed with stepwise variable
      selection of age, pubertal status, BMI SDS, insulin like growth factor-1, and
      HbA1c. Only BMI SDS was significantly correlated with lumbar spine BMD z-score
      (beta=0.395, P=0.023). CONCLUSION: Prepubertal children with newly diagnosed type
      1 DM had similar bone mass compared to healthy peers. However, patients with low
      BMI should be carefully monitored for bone density in type 1 DM.

PMID- 30286570
TI  - Thyroid function in obese Korean children and adolescents: Korea National Health
      and Nutrition Examination Survey 2013-2015.
AB  - PURPOSE: In recent years, there has been an increasing focus on thyroid function
      in pediatric obese patients, but no nationwide study evaluating the relationship
      between thyroid function and obesity has yet been conducted in Korea. We aimed to
      evaluate thyroid dysfunction in obese Korean children. METHODS: We analyzed the
      associations between obesity and thyroid hormone levels among 975 Korean boys and
      girls aged 10-18 years and who participated in the Korean National Health and
      Nutrition Examination Survey VI (2013-2015). RESULTS: Average serum thyrotropin
      (TSH) and serum free thyroxine (fT4) levels in the nonobese group were 2.7+/-0.1
      MUIU/mL and 1.3+/-0.0 ng/dL, respectively, and those in the overweight group were
      3.1+/-0.2 MUIU/mL and 1.2+/-0.0 ng/dL. Serum TSH level was significantly higher
      in the abdominal obesity group than in the normal group (P=0.023). fT4 level was
      significantly lower in both the overweight and abdominal obesity groups than in
      the normal group (P<0.001, P=0.014). Serum TSH level was associated positively
      with abdominal obesity and levels of high-density lipoprotein cholesterol and
      triglyceride. Serum fT4 level was negatively correlated with abdominal obesity
      (P=0.014). CONCLUSION: Korean children with abdominal obesity showed increased
      TSH and decreased fT4 levels compared to normal children.

PMID- 30286571
TI  - Factors affecting height velocity in normal prepubertal children.
AB  - PURPOSE: To analyze the effects of clinical and laboratory factors, including
      insulinlike growth factor (IGF) levels, on the height velocity of normal
      prepubertal children. METHODS: Ninety-five healthy prepubertal children (33 boys,
      62 girls) were enrolled. The mean chronological age was 6.3+/-1.4 years, with a
      height standard deviation score (SDS) of -0.88+/-0.70. IGF-1, IGF binding protein
      3 (IGFBP-3), SDS for anthropometric measurements, and changes in SDS for
      anthropometric measurements were analyzed for 1 year, and their associations with
      1-year height velocity were investigated. RESULTS: The group of children with a 1
      year height velocity of >=6 cm were chronologically younger than the group with a
      1-year height velocity of <6 cm (5.9+/-1.3 years vs. 6.7+/-1.3 years, P=0.004),
      with a lesser increase of SDS for body mass index (BMI) over 1 year (-0.18+/-0.68
      vs. 0.13+/-0.53, P=0.014). There were no differences between the 2 groups in IGF
      1 SDS and IGFBP-3 SDS. Multiple linear regression showed that baseline
      chronological age (r=0.243, P=0.026) and height SDS (r=0.236, P=0.030) were
      positively associated with IGF-1 SDS. Binomial logistic regression showed that an
      older chronologic age at referral (odds ratio [OR], 0.68; 95% confidence interval
      [CI], 0.47-0.99) and an increase of BMI SDS over 1 year (OR, 0.41; 95% CI, 0.18
      0.89) were associated with a decreased growth possibility of an above-average
      height velocity (>=6 cm/yr). CONCLUSION: Height velocity of normal prepubertal
      children is affected by an increase of BMI SDS and chronological age. Prepubertal
      IGF-1 SDS reflects height SDS at the time of measurement but is not associated
      with subsequent height velocity.

PMID- 30286572
TI  - Successful switching from insulin to sulfonylurea in a 3-month-old infant with
      diabetes due to p.G53D mutation in KCNJ11.
AB  - Permanent neonatal diabetes mellitus is most commonly caused by mutations in the
      ATP-sensitive potassium channel (KATP) subunits. Prompt initiation of
      sulfonylurea treatment can improve glycemic control in children with KCNJ11
      mutation. In this report, we present a case of permanent neonatal diabetes caused
      by a mutation in the KCNJ11 gene that was successfully treated via early
      switching of insulin to sulfonylurea treatment. A 53-day-old female infant
      presented with diabetic ketoacidosis. Insulin was administered for the
      ketoacidosis and blood glucose regulation. At 3 months of age, using genomic DNA
      extracted from peripheral lymphocytes, direct sequencing of KCNJ11 identified a
      heterozygous mutation of c.158G>A (p.G53D) and confirmed the diagnosis of
      permanent neonatal diabetes mellitus. Subsequently, treatment with sulfonylurea
      was initiated, and the insulin dose was gradually tapered. At 4 months of age,
      insulin therapy was discontinued, and sulfonylurea (glimepiride, 0.75 mg/kg) was
      administered alone. At 6 months after initiation of administration of
      sulfonylurea monotherapy, blood glucose control was stable, and no hypoglycemic
      events or developmental delays were reported. C-peptide levels increased during
      treatment with sulfonylurea. Early switching to sulfonylurea in infants with
      permanent diabetes mellitus owing to a KCNJ11 mutation could successfully help
      regulate glycemic control, which suggests the need for early genetic testing in
      patients presenting with diabetes before 6 months of age.

PMID- 30286573
TI  - Compound heterozygosity for a whole gene deletion and p.R124C mutation in CYP21A2
      causing nonclassic congenital adrenal hyperplasia.
AB  - We present a family with 2 members who received long-term steroid treatment for
      presumed classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase
      deficiency, until molecular testing revealed nonclassic CAH, not necessarily
      requiring treatment. A 17-year-old male presented to our clinic on glucocorticoid
      and mineralocorticoid treatment for classic CAH. He was diagnosed at 4 years of
      age based on mild-moderate elevations of 17-hydroxyprogesterone (17-OHP) and
      adrenocorticotropic hormone (ACTH), but without evidence of precocious
      adrenarche/puberty. Due to his diagnosis, his clinically asymptomatic 3-year-old
      sister was tested and also found to have elevated ACTH and 17-OHP levels and was
      started on glucocorticoids for classic CAH. Family history revealed a healthy
      sibling who had no biochemical evidence of CAH and consanguineous healthy
      parents. We questioned the diagnosis of classic CAH and performed an ACTH1-24
      stimulation test, which showed a level of 17-OHP in the borderline range between
      classic and nonclassic CAH. Molecular testing, using sequencing and multiplex
      ligation-dependent probe amplification analysis of CYP21A2, revealed that both
      affected siblings were compound heterozygotes for a whole-gene deletion and a,
      likely pathogenic (nonclassical), sequence variant, p.R124C. The asymptomatic
      father had the same genotype, while the mother showed one deleted copy and 2
      active copies, making her an asymptomatic carrier. Our report demonstrates the
      importance of molecular testing in atypical cases of CAH, as well as the
      importance of both sequencing and deletion analysis. The results of molecular
      testing should be interpreted in clinical context, and treatment should be
      prescribed according to guidelines when available.

PMID- 30286575
TI  - A case of Wolfram syndrome with chronic renal failure.

PMID- 30286574
TI  - Testicular microlithiasis in a boy with X-linked adrenal hypoplasia congenita.
AB  - X-linked adrenal hypoplasia congenita (AHC) is a rare disorder that usually
      presents clinically as adrenal insufficiency in early infancy. It is caused by
      mutations in the NR0B1 gene which is located on the short arm of chromosome X
      (Xp21). The NR0B1 gene plays an important role in normal development and function
      of both the adrenal and gonadal axes and some patients with the disease can
      present in adolescence with hypogonadotropic hypogonadism. Testicular
      microlithiasis is an ultrasonographic finding of unknown etiology that has been
      associated with several benign conditions such as cryptorchidism, congenital
      adrenal hyperplasia, varicoceles, and testicular malignancy. We report the case
      of an 11-year-old boy who was diagnosed at the age of 8 months with X-linked AHC
      due to adrenal failure and presented testicular microlithiasis during follow-up.
      To the best of our knowledge, this is the first case of an X-linked AHC patient
      diagnosed with testicular microlithiasis in follow-up.

PMID- 30286576
TI  - Deepening Knowledge Through Basic and Clinical Research.

PMID- 30286577
TI  - Virtual Reality and Simulation for Progressive Treatments in Urology.
AB  - In urology technologies and surgical practices are constantly evolving and
      virtual reality (VR) simulation has become a significant supplement to existing
      urology methods in the training curricula of urologists. However, new
      developments in urology also require training and simulation for a wider
      application. In order to achieve this VR and simulation could play a central
      role. The purpose of this article is a review of the principal applications for
      VR and simulation in the field of urology education and to demonstrate the
      potential for the propagation of new progressive treatments. Two different cases
      are presented as examples: exposure therapy for paruresis and virtual cystoscopy
      for diagnosis and surgery of bladder cancer. The article uses research and
      publications listed in openly accessible directories and is organized into 3
      sections: The first section covers features of VR and simulation technologies.
      The second one presents confirmed applications of current technologies in urology
      education and showcases example future applications in the domain of bladder
      treatment and surgery. The final section discusses the potential of the
      technology to improve health care quality.

PMID- 30286578
TI  - High Estradiol Differentially Affects the Expression of the Glucose Transporter
      Type 4 in Pelvic Floor Muscles of Rats.
AB  - PURPOSE: To characterize the relationship between serum estradiol levels and the
      expression of glucose transporter type 4 (Glut4) in the pubococcygeus and
      iliococcygeus muscles in female rats. METHODS: The muscles were excised from
      virgin rats during the metestrus and proestrus stages of the estrous cycle, and
      from sham and ovariectomized rats implanted with empty or estradiol benzoate
      filled capsules. The expression of estrogen receptors (ERs) was inspected in the
      muscles at metestrus and proestrus. Relative Glut4 expression, glycogen content,
      and serum glucose levels were measured. Appropriate statistical tests were done
      to identify significant differences (P<=0.05). RESULTS: The pubococcygeus and
      iliococcygeus muscles expressed ERalpha and ERbeta. Glut4 expression and glycogen
      content in the pubococcygeus muscle were higher at proestrus than at metestrus.
      No significant changes were observed in the iliococcygeus muscle. In
      ovariectomized rats, the administration of estradiol benzoate increased Glut4
      expression and glycogen content in the pubococcygeus muscle alone. CONCLUSION:
      High serum estradiol levels increased Glut4 expression and glycogen content in
      the pubococcygeus muscle, but not in the iliococcygeus muscle.

PMID- 30286579
TI  - Neonatal Bladder Irritation Is Associated With Vanilloid Receptor TRPV1
      Expression in Adult Rats.
AB  - PURPOSE: To evaluate whether mild chemical irritation of the bladder in neonatal
      rats is associated with persistent vanilloid receptor transient receptor
      potential vanilloid subfamily 1 (TRPV1) activity in adult rats. METHODS: Female
      Sprague-Dawley rats were used. Ten-day-old rat pups underwent bladder
      sensitization via intravesical infusion of 0.2% acetic acid in saline with or
      without prior bladder desensitization with capsaicin. After 8 weeks, 3 groups of
      rats (control [group 1], bladder sensitization [group 2], and bladder
      desensitization [group 3]) underwent cystometry. Inflammation of bladder tissue
      and the expression of TRPV1 in bladder tissue and dorsal root ganglia (DRG) were
      also evaluated. RESULTS: The bladder sensitization group showed more frequent
      voiding contractions. TRPV1 expression in adult bladder tissue was elevated in
      group 2. TRPV1 mRNA levels in the bladder and DRG were significantly higher in
      group 2 than in group 1. Moreover, group 2 had significantly more DRG neurons
      (identified by uptake of the retrograde label Fast Blue) that exhibited TRPV1
      immunoreactivity. CONCLUSION: We found a significant association between neonatal
      bladder sensitization and persistent TRPV1 activity in adult rats. This is the
      first study to focus on the underlying pathogenesis of bladder overactivity from
      childhood to adulthood. Our findings could lead to the development of new
      strategies for the treatment and prevention of adult urinary symptoms arising
      from childhood urinary tract dysfunction.

PMID- 30286580
TI  - Treatment of Anterior Vaginal Wall Prolapse Using Transvaginal Anterior Mesh With
      Apical Fixation: A Prospective Multicenter Study With up to 2 Years of Follow-up.
AB  - PURPOSE: To evaluate the safety and efficacy of a surgical polypropylene mesh for
      correction of anterior vaginal prolapse, with or without apical defects, by
      providing simultaneous reinforcement at the anterior and apical aspects of the
      vagina with a single-incision approach. METHODS: This was a prospective,
      multicenter, single-arm study involving women with baseline stage >=2 anterior
      and/or apical vaginal wall prolapse according to the Pelvic Organ Prolapse
      Quantification (POP-Q) system. The primary endpoint was defined as achievement of
      POP-Q stage <=1 status. Additionally, patient-reported outcomes were assessed
      using the International Consultation on Incontinence Questionnaire-Vaginal
      Symptoms (ICIQ-VS). The device under evaluation was Calistar A, which is fixed
      posteriorly to the sacrospinous ligaments with a novel tissue-anchoring system
      (TAS) and anteriorly to the obturator internus muscles. Postoperative follow-ups
      were scheduled at 7 days and at 6, 12, and 24 months. RESULTS: Ninety-seven women
      were treated and assessed for the primary outcome. They were followed for up to 2
      years (n=43), with a median of 12 months. Objective cure was achieved in 86 of
      the 97 patients (88.7%) (P<0.0005). The mean reduction in the ICIQ-VS scores was
      in the range of 70%-90% for every time point (P<0.05). No bleeding or surgical
      revision was reported. Mesh exposure occurred in 7 patients (7.2%), urinary
      retention in 5 (5.2%), de novo dyspareunia in 3 (3.1%), and urinary tract
      infections in 7 (7.2%). CONCLUSION: This midterm follow-up showed that apical and
      anterior vaginal reinforcement with a polypropylene implant fixed with a TAS
      provided good anatomical correction, with no major complications.

PMID- 30286582
TI  - Factors Influencing Lower Urinary Tract Symptoms in Advanced Cancer Patients With
      Chemotherapy-Induced Peripheral Neuropathy.
AB  - PURPOSE: This study aimed to investigate the severity of lower urinary tract
      symptoms (LUTS) and to identify factors that influenced LUTS in advanced cancer
      patients with chemotherapy-induced peripheral neuropathy (CIPN). METHODS: This
      cross-sectional study included a total of 158 advanced cancer patients with CIPN.
      A structured questionnaire including the International Prostate Symptom Score and
      the Functional Assessment of Cancer Therapy/Gynecology Oncology
      Group/Neurotoxicity scale was used. Data were analyzed using the Pearson
      correlation coefficient and multiple regression analysis. RESULTS: Nocturia was
      the most prevalent LUTS. A positive relationship was found between CIPN symptoms
      and LUTS. The duration of cancer diagnosis and the severity of CIPN were key
      factors that influenced LUTS. CONCLUSION: The severity of CIPN symptoms was the
      most important predictor of LUTS. Nurses' care for advanced cancer patients
      should incorporate a comprehensive health assessment, which includes a history of
      treatment and physical neuropathic symptoms, for any patient complaining of CIPN
      symptoms.

PMID- 30286581
TI  - Specificity of Lower Urinary Tract Symptoms in Neuromyelitis Optica in Comparison
      With Multiple Sclerosis Patients.
AB  - PURPOSE: The aim of this study was to describe lower urinary tract symptoms in
      neuromyelitis optica (NMO), and to compare these data with urinary disorders
      observed in multiple sclerosis (MS) patients. METHODS: Retrospective study of
      data collected from January 1997 to July 2017 using the database from a Neuro
      Urology Department of a university hospital. NMO and MS patients were matched for
      sex, age, and Expanded Disability Status Scale (EDSS). RESULTS: Twenty-six
      patients with NMO were included and compared with 33 MS patients. Mean age was
      41.6 years (standard deviation [SD], 14,8), mostly female patients (24 vs. 2
      males). Mean EDSS was 4.6 (SD, 1.8) in the 2 groups. In NMO group, 57% of the
      patients (n=15) had overactive bladder with urgency and urge incontinence and
      38.5% (n=10) of them had nocturia. Voiding symptoms was observed in 69.2% of the
      patients (n=18); 42.3% of NMO patients performed self-intermittent
      catheterization versus 12.1% in MS patients (P=0.012). Low bladder compliance and
      severe urinary tract infections (pyelonephritis) were more frequent in NMO than
      in MS patients (respectively 15% vs. 0%, P=0.016 and 42% vs. 12%, P=0.024).
      CONCLUSION: Lower urinary tract symptoms, especially overactive bladder and
      urinary retention, are frequent in NMO. Low bladder compliance, serious urinary
      infections, and high prevalence of urinary retention requiring self-intermittent
      catheterization are the main symptoms significantly more frequent than in MS.

PMID- 30286583
TI  - Factors Associated With Early Recovery of Stress Urinary Incontinence Following
      Holmium Laser Enucleation of the Prostate in Patients With Benign Prostatic
      Enlargement.
AB  - PURPOSE: To investigate factors associated with early recovery of stress urinary
      incontinence (SUI) following holmium laser enucleation of the prostate (HoLEP) in
      patients with benign prostatic enlargement (BPE). METHODS: The medical records of
      393 patients who underwent HoLEP for BPE were retrospectively reviewed. Patients
      with SUI following HoLEP were selected and divided into 2 groups: those who
      experienced early recovery of SUI and those who experienced persistent SUI.
      Recovery of SUI within 1 month after HoLEP was defined as early, and SUI that
      remained present after 1 month was defined as persistent. Preoperative clinical
      and urodynamic factors, as well as perioperative factors, were compared between
      groups. RESULTS: SUI following HoLEP was detected in 86 patients. Thirty-three
      patients exhibited recovery of SUI within 1 month, and SUI remained present in 53
      patients after 1 month. Multivariate analysis showed that the transition zone
      prostate volume (odds ratio [OR], 5.354; 95% confidence interval [CI], 1.911
      14.999; P=0.001) and the enucleation ratio (OR, 8.253; 95% CI, 1.786-38.126;
      P=0.007) were significantly associated with early recovery of SUI. CONCLUSION:
      Early recovery of SUI within 1 month following HoLEP was associated with
      transition zone prostate volume and the enucleation ratio.

PMID- 30286584
TI  - Predictors of Nerve Stimulator Success in Patients With Overactive Bladder.
AB  - PURPOSE: To identify factors associated with successful sacral nerve stimulator
      (SNS) trial after SNS implantation for the treatment of medication refractory
      overactive bladder (OAB). METHODS: Patients undergoing treatment for OAB at Lahey
      Hospital and Medical Center between 2004 and 2016 were identified. Patients
      undergoing SNS placement were identified; SNS success was defined as permanent
      implantation of the SNS. Demographic, clinical and treatment data were extracted
      from patient charts; uni- and multivariate analyses were conducted to identify
      factors associated with SNS treatment success. RESULTS: A total of 128 patients
      were included. On univariate analysis, male sex, prior diagnosis of benign
      prostatic hyperplasia, and lower volume at first urge on urodynamics (UDS) were
      associated with unsuccessful SNS trial. On multivariate analysis, male sex (odds
      ratio [OR], 0.145; 95% confidence interval [CI], 0.036-0.530) and lower volume at
      first urge on UDS (OR, 0.982; 95% CI, 0.967-0.995) were associated with
      unsuccessful SNS trial. A threshold value of 100 mL at first urge during
      preoperative UDS had a specificity of 0.86 in predicting SNS success in men.
      CONCLUSION: SNS is frequently successful at relieving OAB symptoms. Male patients
      and those with lower volumes at first urge on UDS, particularly below 100 mL, are
      more likely to have an unsuccessful SNS trial. Patients in these groups should be
      counseled on the lower likelihood of SNS success.

PMID- 30286585
TI  - Sex Differences in Lower Urinary Tract Symptoms in Older Korean Adults Living in
      Rural Areas: Prevalence, Quality of Life, and Associated Factors.
AB  - PURPOSE: Urinary incontinence (UI) is associated with nursing home admission,
      functional decline, and risk of death among community-dwelling older adults.
      Little information, however, is available on sex differences in lower urinary
      tract symptoms (LUTS) in older Korean adults exclusively living in rural areas.
      This study examined sex-related differences in LUTS, factors associated with UI
      in older adults living in rural areas, and health-related quality of life (HRQoL)
      in incontinent older adults. METHODS: This was a cross-sectional study in which
      face-to-face interviews were conducted at 15 rural community-health centres. A
      total of 323 older adults aged >=65 years from rural areas of Korea participated.
      LUTS prevalence was evaluated and HRQoL was measured using the King's Health
      Questionnaire. The chi-square test and t -test were used to examine sex
      differences in characteristics, LUTS, and HRQoL. Multivariable logistic
      regression was used to identify risk factors associated with UI. RESULTS:
      Nocturia was the most prevalent symptom, affecting 87% of men and 86% of women.
      Women (53%) had significantly more UI of any kind than did men (35%) (P=0.007).
      Urgency UI was the most frequent type of UI in men, whereas stress UI was the
      most frequent in women. Regarding HRQoL, men had significantly higher scores in
      the domains of sleep/energy disturbances (P=0.032) than did women, and women
      reported greater effects from the severity of incontinence (P=0.001) than did
      men. Arthritis was the only factor associated with UI in men (odds ratio [OR],
      6.88; 95% confidence interval [CI], 1.46-32.36). However, women with diabetes
      mellitus were less likely to have UI than those without (OR, 0.43; 95% CI, 0.23
      0.82). CONCLUSION: LUTS were found to be highly prevalent in community-dwelling
      older Korean adults in rural areas. Interventions to improve sleep and to reduce
      UI severity are needed for incontinent men and women, respectively.

PMID- 30286587
TI  - Reminiscing on 35 years with Environmental Toxicology in Korea.

PMID- 30286586
TI  - Exosomes as a Communication Tool Between the Lymphatic System and Bladder Cancer.

PMID- 30286588
TI  - Comparison of volatile organic compounds between cigarette smoke condensate (CSC)
      and extract (CSE) samples.
AB  - Cigarette smoke is a major risk factor for several diseases, including chronic
      obstructive pulmonary and cardiovascular diseases. The toxicity of the cigarette
      smoke can be determined in vitro. The cytotoxicity test of the cigarette smoke is
      commonly conducted using the cigarette smoke condensate (CSC) and cigarette smoke
      extract (CSE). The CSC and CSE methods are well known for sampling of the
      particles and water-soluble compounds in the cigarette smoke, respectively. In
      this study, the CSC and CSE were analyzed by using a gas chromatography-mass
      spectrometry (GC-MS) system equipped with a wax column for separation of the
      volatile organic compounds. The cytotoxic effect of the CSC and CSE were
      evaluated thoroughly by comparing the analytical results of the CSC and CSE
      samples. The total concentration of the volatile organic compounds detected in
      the CSC sample was similar to that in the CSE sample based on the peak area.
      Except for the dimethyl sulfoxide solvent, nicotine had the highest concentration
      in the CSC sample, while acetonitrile had the highest concentration in the CSE
      sample. The compositions were as follows: (1) CSC sample: 55.8% nicotine, 18.0%
      nicotyrine, 3.20% 1,2,3-propanetriol, triacetate, 1.28% ethyl chloride, 1.22%
      phenol, etc. and (2) CSE sample: 18.7% acetonitrile, 18.0% acetone, 12.5% 2
      hydroxy-2-methyl-propanenitrile, 8.98% nicotine, 5.86% nicotyrine, etc. In this
      manner, to accurately examine the cytotoxicity of the cigarette smoke using CSC
      or CSE, the components and their concentrations in the CSC and CSE samples should
      be considered.

PMID- 30286589
TI  - Occurrence of microplastics in municipal sewage treatment plants: a review.
AB  - Municipal sewage treatment plants (STPs) are thought to be important point
      sources of microplastics in freshwater systems and many peer-reviewed articles
      have been published on this issue since mid-2010s. In this review, we summarize
      existing literature on the occurrence of microplastics in STPs and experimental
      methods used for isolation and identification of microplastics. The number
      concentrations of microplastics in STP influents were 15.1-640 L-1 , whereas
      those in the STP effluents were highly variable and ranged from not detectable to
      65 L-1 . For most of cases, conventional STPs are removing microplastics very
      effectively. Fragments and fibers are dominant shapes of microplastics.
      Thermoplastics (polyethylene and polypropylene) and polyester are the predominant
      materials recovered. Although further research is needed, size distribution of
      microplastics in STPs is likely to follow a power law, implying that different
      studies using different size cutoffs may be compared after establishing a power
      law relationship.

PMID- 30286590
TI  - A review of current studies on cellular and molecular mechanisms underlying
      pulmonary fibrosis induced by chemicals.
AB  - Several studies showed that the inflammatory and fibrotic responses induced by
      polyhexamethylene guanidine phosphate (PHMG-p) were similar to those observed for
      idiopathic pulmonary fibrosis in South Korea in 2011. "Omic" technologies can be
      used to understand the mechanisms underlying chemical-induced diseases. Studies
      to determine the toxicity of chemicals may facilitate understanding of the
      mechanisms underlying the development of pulmonary fibrosis at a molecular level;
      thus, such studies may provide information about the toxic characteristics of
      various substances. In this review, we have outlined the cellular and molecular
      mechanisms underlying idiopathic pulmonary fibrosis and described pulmonary
      fibrosis induced by various chemicals, including bleomycin, paraquat, and PHMG-p,
      based on the results of studies performed to date.

PMID- 30286592
TI  - Ginkgo biloba extract (EGb761) did not express estrogenic activity in an immature
      rat uterotrophic assay.
AB  - Ginkgo biloba is a dioecious tree that has been used in traditional Chinese
      medicine for about 5,000 years. In previous studies on ginkgo biloba extract
      (EGb761) using in vitro systems, we confirmed that EGb761 has biphasic effects on
      estrogenicity. In this study, we evaluated the agonistic and antagonistic
      activities of EGb761 using a uterotrophic assay in immature female rats. To
      evaluate agonistic and antagonistic effects of EGb761 on uterus, 21-day-old
      immature Sprague-Dawley (SD) female rats were treated with EGb761 (100, 200, or
      400 mg/kg) by oral gavage, 10 MUg/kg of estradiol (E2) or 1 mg/kg tamoxifen (TM)
      by subcutaneous injection, or with EGb761 plus E2 or TM for 3 consecutive days.
      At the end of the treatment period, animals were sacrificed and their body
      weights and organ weights (liver, lung, spleen and kidney) were measured. In
      addition, estrogen-related gene expressions (IGFBP-1 in liver and CaBP-9 in
      uterus) were determined. During the experiment, no animal showed clinical signs,
      a change in body weight or died. EGb761 treatment alone had no effect on
      absolute/relative uterine weight, luminal epithelial cell height (LECH, MUm), or
      luminal circumference (LC, MUm). In addition, uterine weights, LECHs, and LC
      induced by E2 or TM were not significantly changed by EGb761 at any dose. These
      results collectively suggested EGb761 has no agonistic/antagonistic effects in
      utero.

PMID- 30286591
TI  - Epigenetic profiling to environmental stressors in model and non-model organisms:
      Ecotoxicology perspective.
AB  - Epigenetics, potentially heritable changes in genome function that occur without
      alterations to DNA sequence, is an important but understudied component of
      ecotoxicology studies. A wide spectrum of environmental challenge, such as
      temperature, stress, diet, toxic chemicals, are known to impact on epigenetic
      regulatory mechanisms. Although the role of epigenetic factors in certain
      biological processes, such as tumourigenesis, has been heavily investigated, in
      ecotoxicology field, epigenetics still have attracted little attention. In
      ecotoxicology, potential role of epigenetics in multi- and transgenerational
      phenomenon to environmental stressors needs to be unrevealed. Natural variation
      in the epigenetic profiles of species in responses to environmental stressors,
      nature of dose-response relationships for epigenetic effects, and how to
      incorporate this information into ecological risk assessment should also require
      attentions. In this review, we presented the available information on epigenetics
      in ecotoxicological context. For this, we have conducted a systemic review on
      epigenetic profiling in response to environmental stressors, mostly chemical
      exposure, in model organisms, as well as, in ecotoxicologically relevant wildlife
      species.

PMID- 30286593
TI  - What Explains Socioeconomic Inequality in Health-related Quality of Life in Iran?
      A Blinder-Oaxaca Decomposition.
AB  - OBJECTIVES: This study aimed to explain the health-related quality of life
      (HRQoL) gap between the poorest and the wealthiest quintiles in the capitals of
      Kermanshah and Kurdistan Provinces (Kermanshah and Sanandaj), in western Iran.
      METHODS: This was a cross-sectional study conducted among 1772 adults. Data on
      socio-demographic characteristics, socioeconomic status (SES), lifestyle factors,
      body mass index, and HRQoL of participants were collected using a self
      administered questionnaire. The slope and relative indices of inequality (SII and
      RII, respectively) were employed to examine socioeconomic inequality in poor
      HRQoL. Blinder-Oaxaca (BO) decomposition was used to quantify the contribution of
      explanatory variables to the gap in the prevalence of poor HRQoL between the
      wealthiest and the poorest groups. RESULTS: The overall crude and age-adjusted
      prevalence of poor HRQoL among adults was 32.0 and 41.8%, respectively. The SII
      and RII indicated that poor HRQoL was mainly concentrated among individuals with
      lower SES. The absolute difference (%) in the prevalence of poor HRQoL between
      the highest and lowest SES groups was 28.4. The BO results indicated that 49.9%
      of the difference was explained by different distributions of age, smoking
      behavior, physical inactivity, chronic health conditions, and obesity between the
      highest and lowest SES groups, while the remaining half of the gap was explained
      by the response effect. CONCLUSIONS: We observed a pro-rich distribution of poor
      HRQoL among adults in the capitals of Kermanshah and Kurdistan Provinces.
      Policies and strategies aimed at preventing and reducing smoking, physical
      inactivity, chronic health conditions, and obesity among the poor may reduce the
      gap in poor HRQoL between the highest and lowest SES groups in Iran.

PMID- 30286594
TI  - Increased Prevalence of Chronic Disease in Back Pain Patients Living in Car
      dependent Neighbourhoods in Canada: A Cross-sectional Analysis.
AB  - OBJECTIVES: Chronic diseases, including back pain, result in significant patient
      morbidity and societal burden. Overall improvement in physical fitness is
      recommended for prevention and treatment. Walking is a convenient modality for
      achieving initial gains. Our objective was to determine whether neighbourhood
      walkability, acting as a surrogate measure of physical fitness, was associated
      with the presence of chronic disease. METHODS: We conducted a cross-sectional
      study of prospectively collected data from a prior randomized cohort study of 227
      patients referred for tertiary assessment of chronic back pain in Ottawa, ON,
      Canada. The Charlson Comorbidity Index (CCI) was calculated from patient
      completed questionnaires and medical record review. Using patients' postal codes,
      neighbourhood walkability was determined using the Walk Score, which awards
      points based on the distance to the closest amenities, yielding a score from 0 to
      100 (0- 50: car-dependent; 50-100: walkable). RESULTS: Based on the Walk Score,
      134 patients lived in car-dependent neighborhoods and 93 lived in walkable
      neighborhoods. A multivariate logistic regression model, adjusted for age,
      gender, rural postal code, body mass index, smoking, median household income,
      percent employment, pain, and disability, demonstrated an adjusted odds ratio of
      2.75 (95% confidence interval, 1.16 to 6.53) times higher prevalence for having a
      chronic disease for patients living in a car-dependent neighborhood. There was
      also a significant dose-related association (p=0.01; Mantel-Haenszel chi
      square=6.4) between living in car-dependent neighbourhoods and more severe CCI
      scores. CONCLUSIONS: Our findings suggest that advocating for improved
      neighbourhood planning to permit greater walkability may help offset the burden
      of chronic disease.

PMID- 30286596
TI  - Demographic and Survivorship Disparities in Non-muscle-invasive Bladder Cancer in
      the United States.
AB  - OBJECTIVES: To examine survivorship disparities in demographic factors and risk
      status for non-muscle-invasive bladder cancer (NMIBC), which accounts for more
      than 75% of all urinary bladder cancers, but is highly curable with early
      identification and treatment. METHODS: We used the US National Cancer Institute's
      Surveillance, Epidemiology, and End Results registries over a 19-year period
      (1988-2006) to examine survivorship disparities in age, sex, race/ethnicity, and
      marital status of patients and risk status classified by histologic grade, stage,
      size of tumor, and number of multiple primary tumors among NMIBC patients (n=29
      326). We applied Kaplan-Meier (K-M) and Cox proportional hazard methods for
      survival analysis. RESULTS: Among all urinary bladder cancer patients, the
      majority of NMIBCs were in male (74.1%), non-Latino white (86.7%), married
      (67.8%), and low-risk (37.6%) to intermediate-risk (44.8%) patients. The mean age
      was 68 years. Survivorship (in median life years) was highest for non-Latino
      white (5.4 years), married (5.4 years), and low-risk (5.7 years) patients (K-M
      analysis, p<0.001). We found significantly lower survivorship for elderly, male
      (female hazard ratio [HR], 0.96), Latino (HR, 1.20), and unmarried (married HR,
      0.93) patients. CONCLUSIONS: Survivorship disparities were ubiquitous across age,
      sex, race/ethnicity, and marital status groups. Non-white, unmarried, and elderly
      patients had significantly shorter survivorship. The implications of these
      findings include the need for a heightened focus on health policy and more
      organized efforts to improve access to care in order to increase the chances of
      survival for all patients.

PMID- 30286595
TI  - The Role of Social Support and the Neighborhood Environment on Physical Activity
      in Low-income, Mexican-American Women in South Texas.
AB  - OBJECTIVES: To determine the relationships between physical activity (PA), the
      neighborhood environment support for PA, and social support for PA among Mexican
      American women living in South Texas. The Enlace study was a randomized
      controlled trial that tested the effectiveness of a promotora-led PA intervention
      among low-income Mexican origin women (n=614) living in colonias. METHODS: The
      dependent measures included accelerometer-measured average moderate to vigorous
      physical activity (MVPA) and sedentary breaks and the Community Health Activities
      Model Program for Seniors PA 41-item questionnaire. The independent measures
      included the Physical Activity and Neighborhood Environment Scale (PANES) and the
      13-item Physical Activity Social Support (PASS) scale. RESULTS: Enlace
      participants were on average 40.4 (standard deviation, 10.3) years old, born in
      Mexico (86.1%), and uninsured (83.1%). Adjusted linear regression results
      indicated that each 1-point increment in the PANES overall score was associated
      with 0.050 (p<0.001) unit increase in sedentary break and a -0.043 (p=0.001) unit
      decrease in sedentary break duration. Both PANES (beta=0.296; p=0.002) and PASS
      scores (beta=0.076; p<0.001) were associated with weekly average self-reported
      MVPA. Interaction effects were observed between PASS scores and accelerometer
      measured frequency of sedentary breaks and sedentary time duration. CONCLUSIONS:
      The findings of this study indicate that the relationships between PA and built
      environment and social support are measure-dependent and suggest that reducing
      sedentary time in this population may require a closer assessment of social
      support for PA.

PMID- 30286597
TI  - Effect of Uric Acid on the Development of Chronic Kidney Disease: The Korean
      Multi-Rural Communities Cohort Study.
AB  - OBJECTIVES: Several studies have investigated the effects of serum uric acid
      (SUA) levels on chronic kidney disease (CKD), with discrepant results. The effect
      of SUA levels on CKD development was studied in the Korean rural population.
      METHODS: A total of 9695 participants aged >=40 years were recruited from 3 rural
      communities in Korea between 2005 and 2009. Of those participants, 5577 who
      participated in the follow-up and did not have cerebrovascular disease,
      myocardial infarction, cancer, or CKD at baseline were studied. The participants,
      of whom 2133 were men and 3444 were women, were grouped into 5 categories
      according to their quintile of SUA levels. An estimated glomerular filtration
      rate of <60 mL/min/1.73 m2 at the time of follow-up was considered to indicate
      newly developed CKD. The effects of SUA levels on CKD development after adjusting
      for potential confounders were assessed using Cox proportional hazard models.
      RESULTS: Among the 5577 participants, 9.4 and 11.0% of men and women developed
      CKD. The hazard ratio (HR) of CKD was higher in the highest quintile of SUA
      levels than in the third quintile in men (adjusted HR, 1.60; 95% confidence
      interval [CI], 1.02 to 2.51) and women (adjusted HR, 1.56; 95% CI, 1.14 to 2.15).
      Furthermore, CKD development was also more common in the lowest quintile of SUA
      levels than in the third quintile in men (adjusted HR, 1.83; 95% CI, 1.15 to
      2.90). The effect of SUA was consistent in younger, obese, and hypertensive men.
      CONCLUSIONS: Both high and low SUA levels were risk factors for CKD development
      in rural Korean men, while only high levels were a risk factor in their women
      counterparts.

PMID- 30286599
TI  - Necessity of Epigenetic Epidemiology Studies on the Carcinogenesis of Lung Cancer
      in Never Smokers.
AB  - Based on epidemiological and genomic characteristics, lung cancer in never
      smokers (LCNS) is a different disease from lung cancer in smokers. Based on
      current research, the main risk factor for LCNS may be air pollution. A recent
      case-control study in Koreans reported that nitrogen dioxide (NO2) may be a risk
      factor for LCNS. Additionally, a cohort study showed that exposure to NO2 was
      associated with significant hypomethylation. Thus, epigenetic epidemiology
      studies are needed in the near future to evaluate the carcinogenesis of LCNS
      according to chronic exposure to air pollution and/or viral infections.

PMID- 30286598
TI  - National Trends in Smoking Cessation Medication Prescriptions for Smokers With
      Chronic Obstructive Pulmonary Disease in the United States, 2007-2012.
AB  - OBJECTIVES: Smoking cessation decreases morbidity and mortality due to chronic
      obstructive pulmonary disease (COPD). Pharmacotherapy for smoking cessation is
      highly effective. However, the optimal prescription rate of smoking cessation
      medications among smokers with COPD has not been systemically studied. The
      purpose of this study was to estimate the national prescription rates of smoking
      cessation medications among smokers with COPD and to examine any disparities
      therein. METHODS: We conducted a retrospective study using National Ambulatory
      Medical Care Survey data from 2007 to 2012. We estimated the national
      prescription rate for any smoking cessation medication (varenicline, bupropion,
      and nicotine replacement therapy) each year. Multiple survey logistic regression
      was performed to characterize the effects of demographic variables and
      comorbidities on prescriptions. RESULTS: The average prescription rate of any
      smoking cessation medication over 5 years was 3.64%. The prescription rate
      declined each year, except for a slight increase in 2012: 9.91% in 2007, 4.47% in
      2008, 2.42% in 2009, 1.88% in 2010, 1.46% in 2011, and 3.67% in 2012. Hispanic
      race and depression were associated with higher prescription rates (odds ratio
      [OR], 5.15; 95% confidence interval [CI], 1.59 to 16.67 and OR, 2.64; 95% CI,
      1.26 to 5.51, respectively). There were no significant differences according to
      insurance, location of the physician, or other comorbidities. The high OR among
      Hispanic population and those with depression was driven by the high prescription
      rate of bupropion. CONCLUSIONS: The prescription rate of smoking cessation
      medications among smokers with COPD remained low throughout the study period.
      Further studies are necessary to identify barriers and to develop strategies to
      overcome them.

PMID- 30286600
TI  - Molecular Insights into the Unusual Structure of an Antifreeze Protein with a
      Hydrated Core.
AB  - The primary driving force for protein folding is the formation of a well-packed,
      anhydrous core. However, recently, the crystal structure of an antifreeze
      protein, maxi, has been resolved where the core of the protein is filled with
      water, which apparently contradicts the existing notion of protein folding. Here,
      we have performed standard molecular dynamics (MD) simulation, replica exchange
      MD (REMD) simulation, and umbrella sampling using TIP4P water at various
      temperatures (300, 260, and 240 K) to explore the origin of this unusual
      structural feature. It is evident from standard MD and REMD simulations that the
      protein is found to be stable at 240 K in its unusual state. The core of protein
      has two layers of semi-clathrate water separating the methyl groups of alanine
      residues from different helical strands. However, with increasing temperature
      (260 and 300 K), the stability decreases as the core becomes dehydrated, and
      methyl groups of alanine are tightly packed driven by hydrophobic interactions.
      Calculation of the potential of mean force by an umbrella sampling technique
      between a pair of model hydrophobes resembling maxi protein at 240 K shows the
      stabilization of second solvent-separated minima (SSM), which provides a
      thermodynamic rationale of the unusual structural feature in terms of weakening
      of the hydrophobic interaction. Because the stabilization of SSMs is implicated
      for cold denaturation, it suggests that the maxi protein is so designed by nature
      where the cold denatured-like state becomes the biologically active form as it
      works near or below the freezing point of water.

PMID- 30286601
TI  - Finding Free-Energy Landmarks of Chemical Reactions.
AB  - We propose a novel approach to search for free-energy landmarks, i.e., minima and
      the saddle points, of chemical reactions in an automated manner using a
      combination of steepest descent and gentlest ascent methods. A numerical approach
      is suggested to improve the sampling efficiency of the second derivatives of the
      free-energy surface, which is required in the gentlest ascent method. This
      technique opens a way to identify free-energy landmarks of bond-breaking/creating
      processes in which the underlying potential energy surface is described using on
      the-fly electronic structure calculations. As demonstrations of the approach, we
      present applications to the ring-opening of cis-1,2-dimethylbenzocyclobutene
      using the semiempirical PM7 method, focusing on the temperature dependence of the
      paths and barrier of the reaction, and we study an SN2 reaction in aqueous
      solution using a semiempirical QM/MM approach combining PM7 with the TIP3P water
      model.

PMID- 30286602
TI  - A Simple Phase Correction Makes a Big Difference in Nonadiabatic Molecular
      Dynamics.
AB  - The outcomes of nonadiabatic molecular dynamics (NA-MD) calculations are
      modulated by the parameters entering the time-dependent Schrodinger equation (TD
      SE). The adiabatic states are commonly used as the basis in which the TD-SE is
      integrated. However, the phase inconsistencies of such states along the nuclear
      trajectories obtained in NA-MD simulations may render the wave function and other
      relevant properties ill-behaving, adversely affecting the dynamics. This work
      illustrates the consequence of adiabatic state phase inconsistencies in
      nonadiabatic Ehrenfest dynamics. A simple phase-correction approach is proposed
      and is demonstrated to alter the dynamics to make it consistent with the
      reference calculations done in the phase-consistent diabatic representation.

PMID- 30286604
TI  - Retraction of "Dual-Responsive Polymer Coated Superparamagnetic Nanoparticle for
      Targeted Drug Delivery and Hyperthermia Treatment".

PMID- 30286603
TI  - Aristolochic Acids as Persistent Soil Pollutants: Determination of Risk for Human
      Exposure and Nephropathy from Plant Uptake.
AB  - Exposure to aristolochic acids (AAs) from Aristolochia plants is one of the major
      global causes of nephropathy, including Balkan endemic nephropathy (BEN); renal
      failure; and urothelial cancer. The high incidence of BEN on the Balkan Peninsula
      is assumed to result from consumption of Aristolochia clematitis L. seeds
      coharvested with crops. Here, we show that AAs are long-lived soil contaminants
      that enter wheat and maize plants by root uptake with strong pH dependence. Soil
      and crops from Serbian farms in areas endemic for A. clematitis were found to be
      extensively contaminated with AAs, with contamination strongly correlated with
      local incidence of BEN. The persistence of AAs as soil contaminants suggests that
      weed control for A. clematitis plants is needed to reduce the incidence of BEN
      and aristolochic acid nephropathy, systematic surveys of soil and crop AA levels
      would identify high-risk regions, and it is imperative to research soil
      remediation methods.

PMID- 30286605
TI  - Villous adenoma of the choledocho: an infrequent pathology of the main bile duct.
AB  - We present the case of a patient with obstructive jaundice due to a polylobulated
      lesion at the middle common bile duct that is identified as a villous adenoma of
      the main bile duct. This entity is infrequent with few references in the
      bibliography. It is a benign pathology but with risk of malignancy, so the
      diagnosis and resection is essential for adequate treatment.

PMID- 30286606
TI  - Evaluating the role of mindfulness in terms of asthma-related outcomes and
      depression and anxiety symptoms among individuals with asthma.
AB  - The aim of the current study was to examine the unique role of mindfulness skills
      in terms of: (1) asthma-related outcomes (i.e., asthma control, asthma quality of
      life); (2) depression symptoms; and (3) anxiety symptomatology (i.e., anxiety
      sensitivity, panic symptoms, global anxiety) among non-smoking adults with
      current asthma. Participants were 61 (61.9% female; Mage = 34.72 years, SD =
      13.58, range = 18-65) non-smoking adults with current asthma who completed a
      battery of self-report measures. Results indicated that, after controlling for
      the effects of race and age, greater ability to describe present moment
      experiences was significantly associated with better asthma-related quality of
      life and lower levels of anxiety symptoms. Though mindfulness skills together
      were associated with lower levels of panic symptoms, there were no significant
      individual associations between specific skills and panic symptoms. Greater
      nonjudgment of present moment experiences was associated with lower levels of
      anxiety and anxiety sensitivity. Greater nonreactivity was significantly
      associated with lower levels of depression symptoms and anxiety sensitivity.
      Lastly, a greater ability to observe present moment experiences was associated
      with lower levels of anxiety sensitivity. Mindfulness was not significantly
      associated with asthma control. These findings suggest that it may be useful to
      target the mindfulness skills of describing, nonjudgment, and nonreactivity among
      individuals with asthma, particularly those with elevated levels of anxiety and
      depression, in order to improve psychological and asthma-related outcomes.

PMID- 30286607
TI  - Morphological and functional features prognostic factor of magnetic resonance
      imaging in locally advanced rectal cancer.
AB  - Background Although imaging can be suggestive of the diagnosis of rectal cancer,
      the primary imaging role is to assist in treatment triage of histologically
      diagnosed tumors. The possibility of a multimodal approach in the response to the
      treatment opens the way for the selection of criteria more personalized to the
      patient. Purpose To assess the prognostic factor of morphological and functional
      magnetic resonance imaging (MRI) in rectal cancer. Material and Methods Seventy
      seven patients were enrolled and underwent MRI before treatment and 59 patients
      underwent MRI after treatment. Radiologists evaluated the presence of lesions
      using a 4-point confidence scale; they recorded anatomical side, extent, and
      distance from the anorectal junction and distance from the circumferential
      margin. Tumor location was classified according to the involvement of proximal
      rectal channel and/or distal rectal channel. Radiologists scored signal intensity
      on T2-weighted (T2W) images, diffusion-weighted images (DWI), and MRI dynamic
      enhancement pattern. Tumor regression grade (TRG) and pathological T (pT) were
      the gold standard. Results Lesion vascularization score before treatment showed a
      predictive value of complete pathological response (sensitivity 88%, specificity
      50%) based on pT, while using TRG lymph node number before treatment (sensitivity
      83%, specificity 57%) showed a predictive value for response treatment. T2W
      signal (sensitivity 78%, specificity 30%) and DWI signal after treatment
      (sensitivity 78%, specificity 61%) showed a good predictive value for local
      rectal recurrences. Conclusions Lesion vascularization and lymph node number had
      a predictive value for neoadjuvant treatment complete response in rectal cancer.
      T2W signal intensity and DWI signal showed a good predictive value for local
      rectal recurrences.

PMID- 30286609
TI  - The prevalence of depression and insomnia symptoms among patients with rheumatoid
      arthritis and osteoarthritis in Poland: a case control study.
AB  - The objective of the study was to assess the prevalence of symptoms of depression
      and insomnia among patients with rheumatoid arthritis and osteoarthritis in
      comparison with individuals without chronic diseases. The study was carried out
      at National Institute of Geriatrics, Rheumatology and Rehabilitation, included
      229 persons. The participants were divided into the following groups: group I -
      120 patients with rheumatoid arthritis, group II - 58 patients with
      osteoarthritis, group III - 51 healthy individuals no confirmed depression
      (control group). Symptoms of depression were confirmed by a multiple-choice self
      reported Beck Depression Inventory questionnaire. Symptoms of depression
      confirmed with depression inventory>= 10 occurred as follows: patients with
      rheumatoid arthritis - 75.83%, patients with osteoarthritis - 50%, control group 
      23.53% (p<0.0001), with the prevalence of insomnia (AIS>=6) at: 71%, 32% and
      33%, respectively (p<0.001). In group I mean values of FIRST and AIS were 23.06
      and 8.36 respectively, with group II: 21.71 and 7.84, respectively. In all
      subjects with AIS>=6, the depression inventory was statistically significantly
      (p<0.005) higher than in the subjects with AIS<6 (respectively: 17.02 vs 12.13;
      15.6 vs 8.05; 5.45 vs 1.81). Patients with rheumatoid arthritis find it difficult
      to cope with stress. Insomnia as a reaction to stress occurs more often in this
      group.

PMID- 30286608
TI  - Spatial dynamics and epidemiology for AIDS in remote areas in French Guiana.
AB  - Although AIDS care is generally improving in French Guiana, disparities among
      regions and certain key populations remain significant. The purpose of this study
      was to describe the spatial and clinical characteristics of people living with
      HIV (PLHIV) in remote areas in comparison to those followed in hospitals on the
      urban coast of French Guiana. The data presented were obtained from outpatient on
      primary care centers located in rural regions away from the urban coast. Data
      were compared with that from medical records of PLHIV treated in French Guiana's
      urban care. The evolution of the annual rate of discovery of HIV seropositivity
      indicates a lag in remote areas as compared to urban and coastal areas. In recent
      years, the epidemic appeared as particularly active in rural areas among
      Brazilian patients. The median age of PLHIV in remote areas was 43.8 years, the
      sex ratio (M/F) was 0.93. Nearly 37% of PLHIV were discovered with advanced
      disease (<200 CD4/mm3). The percentage of virological success after six months of
      HAART was 80% and 88% in remote areas and urban area, respectively. Efforts must
      be made to control and halt the spread of the HIV epidemic, as these remote sites
      represent strategic points.

PMID- 30286610
TI  - Retaining identity: Creativity and caregiving.
AB  - Arts programming for people living with dementia and their caregivers has gained
      popularity as a way to provide opportunities for social interaction, expression,
      and continual learning. The goal of the present study, referred to as Retaining
      Identity: Creativity & Caregiving is to: (1) describe the process of designing
      and implementing a structured art experience for people living with memory loss
      and their co-residing caregiver; and (2) to summarize feedback provided by
      caregivers at the conclusion of the program. Retaining Identity is an eight-week
      program offered by professional artists who instructed dementia caregivers in
      four visual art activities, which they then taught to their care recipient. The
      program was designed for individuals with no art experience and the art projects
      were carefully developed to be engaging for both people living with dementia and
      their caregivers. The evaluation process included a qualitative survey completed
      by the caregivers to measure the impact of the program on the caregiver/care
      recipient relationship. The main themes that emerged from the survey were:
      caregiver growth, caregiver awareness, and creative discovery. The participants'
      artwork supports that art making has the potential to encourage an equitable
      exchange and outcome for people with memory loss and their caregivers. Although
      the survey is limited in scope, the results support the use of the arts to
      positively impact caregivers and their relationship with their care recipient.

PMID- 30286612
TI  - Evaluation of a Pharmacy-to-Dose Pneumococcal Vaccination Protocol at an Academic
      Medical Center.
AB  - BACKGROUND: In February 2016, a pharmacy-to-dose (PTD) pneumococcal vaccination
      protocol was implemented to aid in the appropriate selection of pneumococcal
      vaccines. OBJECTIVE: The primary objective was to compare the rate of appropriate
      vaccine ordering with the PTD protocol. Secondary objectives were to assess
      vaccine administration rate and determine factors preventing patients from
      receiving the vaccine after appropriate selection. METHODS: This was a single
      center, retrospective cohort study of adult patients admitted to an inpatient
      service. Eligible patients were 19 years of age or older and had either a PTD
      pneumococcal vaccination order placed or an alert triggered indicating that the
      patient was a candidate for a vaccination. Patients were excluded if they had
      contraindications to receiving either pneumococcal vaccine. The Fisher exact test
      was used to evaluate the primary objective, and descriptive statistics were used
      to evaluate the secondary objectives. RESULTS: A total of 327 patients were
      included in the analysis: 167 in the preprotocol cohort and 160 in the
      postprotocol cohort. The correct vaccine ordering rates were found to be 26.9%
      (45/167) and 83.1% (133/160) in the preprotocol and postprotocol cohorts,
      respectively ( P < 0.001). In the postprotocol cohort, 17.5% (28/160) of patients
      did not have a vaccine administered. Reasons for vaccine administration failure
      were identified as patient refusal, patient expired during admission, vaccine not
      dispensed by pharmacy, and vaccine dispensed by pharmacy but returned.
      CONCLUSIONS: The PTD pneumococcal vaccination protocol significantly improved
      correct vaccine ordering rates.

PMID- 30286611
TI  - Acupuncture for Cancer Pain and Symptom Management in a Palliative Medicine
      Clinic.
AB  - OBJECTIVE: Studies suggest acupuncture improves cancer-related symptoms; however,
      it is unclear whether patient characteristics predict pain response. This study
      determined acupuncture's effect on cancer-related pain and identified variables
      associated with pain response. METHODS: A retrospective chart review included
      adult patients with cancer referred to palliative medicine and received
      acupuncture for pain management. Paired t tests compared differences in pain
      scores from pre- to postacupuncture. Clinically meaningful pain improvement was
      defined as >=2-point reduction in pain score. Logistic regression was used to
      evaluate associations between patient characteristics and pain improvement.
      RESULTS: One hundred seventy acupuncture treatments from 68 individual patients
      were studied. Significant reductions in mean pain scores were observed after the
      first treatment (-1.9 +/- 1.8; P < .001) and across all treatments (-1.7 +/- 1.9;
      P < .001). Multivariable analysis demonstrated clinically meaningful pain
      improvement with higher baseline pain scores (odds ratio [OR]: 1.79, 95%
      confidence interval [CI]: 1.44-2.22; P < .001) and stage III/IV disease (OR:
      3.23, 95% CI: 1.11-9.40; P < .001). There were significant improvements in
      anxiety, depression, drowsiness, dyspnea, fatigue, nausea, and well-being after
      the first treatment and across all treatments ( P < .001). CONCLUSIONS:
      Acupuncture improved cancer-related pain and other symptoms. Those with higher
      baseline pain scores and advanced disease were more likely to achieve significant
      pain reduction. Improved depression and fatigue were closely related to pain
      reduction. Further studies are needed to confirm pain response variables,
      establish durability, and develop a personalized approach to acupuncture.

PMID- 30286613
TI  - The Effectiveness of Reality Orientation Therapy in the Treatment of Parkinson
      Disease Dementia.
AB  - Patients with Parkinson disease dementia (PDD) have deficits resulting mainly
      from frontostriatal dysfunction. The aim of this study was to assess the
      effectiveness of reality orientation therapy (ROT) combined with drug therapy
      (acetylcholinesterase inhibitors) in PDD treatment and compare it with that of
      drug therapy alone. Patients (n = 12) with a diagnosis of PDD were divided into 2
      groups: group A-drug therapy and ROT; group B-drug therapy alone. Reality
      orientation therapy was applied weekly for 6 months, and patients were assessed
      during the same period. Significant improvements in frontostriatal deficits were
      observed in the group that received the combined therapy, as shown mainly by the
      scores in verbal fluency in the Consortium to Establish a Registry for
      Alzheimer's Disease (CERAD) battery ( P = .02) and in attention in Scales for
      outcomes of Parkinson's Disease-Cognition ( P = .021) and Clock Drawing Test ( P
      = .037). Patients who received only medication had worse results in
      constructional praxis recall in the CERAD battery ( P = .037). Our results
      indicate that ROT may help in the treatment of frontostriatal cognitive deficits
      and can potentially be used to complement drug therapy.

PMID- 30286614
TI  - Regulatory Requirements and Innovation: A Comparison of the Dermatologic
      Antifungal Drug Product Markets in Brazil and United States.
AB  - BACKGROUND: Development of novel dermatological topical products for the
      treatment of cutaneous fungal infections is a constant necessity, especially in
      developing countries. Through public health policies, many developing countries
      have facilitated in the last decades the entry of generic products, which can be
      superficially seen as a threat to innovation. To verify whether regulatory
      requirements, or the waiving of some requirements, could have an impact on
      innovation, we performed a detailed technical comparison of the dermatologic
      antifungal markets of Brazil and of the United States, taking Brazil as an
      example of a developing country with more lenient requirements regarding the
      registration of generic topical drug products. METHODS: The official databank of
      ANVISA (DATAVISA) and of US Food and Drug Administration (Orange Book) were
      assessed for valid topical dermatological antifungal drug products registered.
      RESULTS: The Brazilian market has a greater number of registered drug products
      encompassing a greater variety of drug substances than the US, but the latter
      comprises more products with novel technologies. In both countries, cream was the
      predominant dosage form and imidazoles were the major substance group.
      Ketoconazole was the lead active substance in Brazil and ciclopirox was the lead
      drug in the US. Generic products dominated both markets. CONCLUSIONS: Despite the
      great number of registered products, the Brazilian market lacks the latest
      technologies, reflecting that the ease of generics registration is not
      accompanied by innovation.

PMID- 30286615
TI  - Clinical Research Coordinators' Attitude Toward Risk-Based Monitoring.
AB  - BACKGROUND: Clinical research coordinators (CRCs) are persons who collect,
      record, and maintain clinical trial data in accordance with the principles of
      Good Clinical Practice at investigators' sites. This study was conducted to
      examine attitudes of clinical research coordinators (CRCs) toward risk-based
      monitoring (RBM) prior to full-scale implementation of RBM in Korea. METHODS: The
      study subjects were 607 CRCs, and data were collected using a self-reported
      questionnaire. Collected data were analyzed by frequency, percentage, chi2 test
      and Fisher exact test. RESULTS: Among CRCs, 42.3% had heard of RBM and 44.6% were
      found to oppose its implementation. Those opposed believed that implementation of
      RBM would increase the workload of CRCs and CRAs' work support for CRCs. In
      addition, they showed many negative opinions such as poor accuracy of test data
      input and failure to increase the overall quality of clinical tests. In
      particular, such attitudes were more noticeable in CRCs with 5 or more years of
      experience. CONCLUSION: Before the implementation of RBM, it is necessary to come
      up with administrative measures such as education for practitioners and
      recruitment of human resources to help CRCs properly understand RBM.

PMID- 30286616
TI  - Sustained exposure to acute migraine medications combined with repeated noxious
      stimulation dysregulates descending pain modulatory circuits: Relevance to
      medication overuse headache.
AB  - Background Loss of conditioned pain modulation/diffuse noxious inhibitory
      controls has been demonstrated in patients with migraine and medication overuse
      headache. We hypothesized that exposure to acute migraine medications may lead to
      dysregulation of central pain modulatory circuits that could be revealed by
      evaluating diffuse noxious inhibitory controls and that prior noxious stimulus is
      required for a loss of the diffuse noxious inhibitory control response in rats
      exposed to these medications. Methods Rats were "primed" by continuous infusion
      of morphine or one of two doses of sumatriptan. Diffuse noxious inhibitory
      control was evaluated at the end of drug-priming (day 7) and again after sensory
      thresholds returned to baseline (day 21). The Randall-Selitto hindpaw pressure
      test was used as the test stimulus and forepaw capsaicin injection served as the
      conditioning stimulus. Results Morphine-primed rats showed opioid-induced
      hyperalgesia accompanied by a loss of diffuse noxious inhibitory controls on day
      7. Sumatriptan-primed rats did not develop hyperalgesia or loss of diffuse
      noxious inhibitory controls on day 7. Morphine-primed and high-dose sumatriptan
      primed rats only had a loss of diffuse noxious inhibitory control on day 21 if
      they received a capsaicin injection on day 7. Conclusions Prolonged exposure to
      migraine treatments followed by an acute nociceptive stimulation caused long
      lasting alterations in descending pain modulation, shown by a loss of diffuse
      noxious inhibitory controls. Morphine was more detrimental than sumatriptan,
      consistent with clinical observations of higher medication overuse headache risk
      with opioids. These data suggest a mechanism of medication overuse headache by
      which migraine medications combined with repeated episodes of pain may amplify
      the consequences of nociceptor activation and increase the probability of future
      migraine attacks as well as risk of medication overuse headache.

PMID- 30286617
TI  - Performance evaluation of the GastroPlusTM software tool for prediction of the
      toxicokinetic parameters of chemicals.
AB  - The accurate prediction of toxicokinetic parameters arising from oral, dermal and
      inhalation routes of chemical exposure is a key element in chemical safety
      assessments. In this research, the physiologically based pharmacokinetic (PBPK)
      GastroPlusTM software was evaluated against a series of chemicals for the
      prediction of toxicokinetic parameters. Overall, 67% of predicted intrinsic
      clearance (Clint) values were within 1- to 10-fold of empirical data for 463
      compounds, and 87% of the predicted fraction unbounded in plasma (Fup) values
      were 1- to 3-fold of empirical data for 441 compounds. The r2 (coefficient of
      determination) of predicted Cmax (maximum plasma concentration) and AUC (Area
      Under Curve) values versus the corresponding empirical values from oral,
      inhalation and dermal exposures ranged from 0.04 to 0.92. Among the three
      exposures, the highest r2 values, ranging from 0.80 to 0.92, were observed for
      oral exposure predictions, where 88% of the compounds had 1- to 10-fold
      differences between predicted and empirical values for Cmax and AUC. The
      predicted plasma Css (steady-state plasma concentration) values were consistent
      with those Css values calculated by in vitro-to-in vivo extrapolation (IVIVE)
      approaches using experimental parameters. Based on the evaluation results,
      GastroPlusTM can be used as a QSAR/PBPK tool for toxicokinetic parameter
      predictions.

PMID- 30286618
TI  - Postgraduate Education in Pharmaceutical Medicine in Australia: Evaluation and
      Evolution to a Global Program Over 20 Years.
AB  - BACKGROUND: The Pharmaceutical Medicine program at the University of New South
      Wales provides postgraduate education for students seeking employment relating to
      development of new medicines and medical technology. The objective of this study
      was to determine which changes to the program were required to meet future
      educational needs of students. METHODS: Responses to questions from 76 students,
      tutors, lecturers, and stakeholders were obtained via Qualtrics surveys. RESULTS:
      Most respondents would recommend the program because of scope and program
      emphasis, content, quality of teaching, flexibility, and availability of distance
      and online content. Students valued links to industry and the national regulatory
      authority. Respondents recommended program content be current, expanded to meet
      needs of the Asia-Pacific region, and structured to ensure opportunities for
      networking and collaboration. CONCLUSIONS: Recommended changes to the program are
      being implemented to optimize skills and knowledge of graduates for roles in
      global pharmaceutical, medical technology, and biotechnology industries.

PMID- 30286620
TI  - Evaluation of Analytical Performance of Three Blood Glucose Monitoring Systems:
      System Accuracy, Measurement Repeatability, and Intermediate Measurement
      Precision.
AB  - INTRODUCTION: Blood glucose monitoring systems (BGMS) should provide sufficient
      analytical quality to allow adequate therapy for diabetes patients. Besides
      system accuracy, measurement precision is an important aspect of a BGMS'
      analytical quality. METHODS: Based on ISO 15197:2013/EN ISO 15197:2015, system
      accuracy, measurement repeatability, and intermediate measurement precision were
      assessed. ISO 15197:2013 system accuracy criteria require that ?95% of individual
      BGMS' test strip lot results shall fall within +/-15 mg/dl or +/-15% of
      corresponding comparison method results (at glucose concentrations <100 mg/dl and
      ?100 mg/dl, respectively), and that ?99% of results fall within consensus error
      grid (CEG) zones A and B. Measurement repeatability was assessed using venous
      blood samples, whereas intermediate measurement precision was assessed using
      control solution samples. Standard deviation (SD) and coefficient of variation
      (CV) were calculated for glucose concentrations <100 mg/dl and ?100 mg/dl,
      respectively. Precision acceptance criteria are not specified by ISO 15197:2013.
      RESULTS: All three BGMS fulfilled system accuracy criteria with 96% to 98% of
      individual test strip lot's results falling within the acceptable accuracy
      limits. All measurement results fell within CEG zones A and B. For measurement
      repeatability, SD was ?3.3 mg/dl, and CV was ?3.9% for the investigated BGMS.
      Assessment of intermediate measurement precision showed SD ?1.3 mg/dl and CV
      ?3.0%. CONCLUSION: All three BGMS fulfilled system accuracy criteria of ISO
      15197:2013. In absence of acceptance criteria, precision results were found to be
      consistent with the manufacturer's labeling of the investigated devices.

PMID- 30286621
TI  - Emotional experience of people with advanced liver disease: Secondary data
      analysis.
AB  - Introduction Patients with advanced liver disease live mainly in the community
      with treatment of complications provided for in-hospital. The illness trajectory
      of advanced liver disease is uncertain and most do not have access to end of life
      care. Gaps in knowledge and understanding of the patient experience of this
      condition have been identified. Methods Secondary analysis of 15 transcripts from
      in-depth interviews with people with advanced liver disease collected as part of
      a previous longitudinal study on the experience of liver disease. Transcripts
      were thematically analysed for emotional content. Results Fear, anger, sadness
      and guilt clearly featured in the person's experience of advanced liver disease.
      Certain causal factors were identified as provoking these emotional responses,
      including shock of diagnosis, uncertainty concerning illness, lack of coordinated
      care, worrying symptoms and sudden death. Humour emerged as a coping mechanism.
      Conclusion People living with advanced liver disease experience distressing
      emotions. It is helpful for clinicians, nurses and other healthcare support staff
      to have an appreciation of the person's emotional concerns in order to provide
      holistic care typical of a palliative approach.

PMID- 30286619
TI  - LINC00673 rs11655237 Polymorphism Is Associated With Increased Risk of Cervical
      Cancer in a Chinese Population.
AB  - Cervical cancer is the fourth most commonly diagnosed cancer and the fourth
      leading cause of cancer deaths in women worldwide. Few single-nucleotide
      polymorphisms associated with risk of cervical cancer have been identified, yet
      genetic predisposition contributes significantly to this malignancy. Long
      noncoding RNA LINC00673 has been widely explored for its role in the development
      and prognosis of many tumors, and 2 genome-wide association studies identified
      that LINC00673 rs11655237 was associated with susceptibility to pancreatic
      cancer. In the current study, using a case-control study design, we found
      rs11655237 significantly increased susceptibility of cervical cancer in a Chinese
      population (odds ratio = 1.27; 95% confidence interval = 1.08-1.50; P = .005).
      Expression of LINC00673 was significantly higher in adjacent normal tissues than
      in paired cancer tissues ( P < .01) and significantly lower in the cancer or
      paired adjacent normal tissues of patients with cervical cancer having rs11655237
      allele A than in those having rs11655237 allele G ( P < .001). Our results
      indicate that LINC00673 rs11655237 is associated with increased risk of cervical
      cancer, possibly by downregulating LINC00673 expression in cervical tissues.

PMID- 30286622
TI  - Progressive freeze concentration of skimmed milk in an agitated vessel: Effect of
      the coolant temperature and stirring rate on process performance.
AB  - The aim of this study was to investigate the freeze-concentration of skimmed milk
      by a progressive freeze concentration process. The progressive freeze
      concentration procedure was performed at three different temperatures (-5, -10,
      and -15 C) and stirring rates (0, 500, and 1000 r/min). The solids concentration
      was determined and used for calculations of the efficiency of the process,
      concentrated yield, and experimental results validation. A general linear model
      was applied to determine the influence of the two factors studied, namely coolant
      temperature and agitation speed. In all tests, it was possible to concentrated
      skimmed milk with total solids content higher (P < 0.05) than ultra-high
      temperature skimmed milk. The highest concentration (P < 0.05) was achieved at
      low coolant temperature (-15 C) and high agitation speed (1000 r/min). The
      coolant temperature and the stirring rate both had a significant effect (P <
      0.05) on the results of efficiency of the process and concentrated yield.
      Nevertheless, the parameter that showed the most significant effect in our study
      was the stirring rate. The tests presented a good fit since the root mean square
      values were below 25%. The freezing point temperatures of the concentrated milk
      fractions were lower than that of skimmed milk. Finally, the best-operating
      conditions in our study were achieved using a high coolant temperature (-5 C) and
      high mechanical stirring (1000 r/min), which was also the variable with the
      lowest (P < 0.05) retention of solids in the ice fraction. In our study, the
      progressive freeze concentration technique showed promise as an alternative for
      the dairy industry since it makes the development of new dairy products possible.

PMID- 30286623
TI  - Modeling of lactic acid fermentation of soy formulation with Lactobacillus
      plantarum HM1.
AB  - Lactic acid bacteria alone or with special adjunct probiotic strains are
      inevitable for the preparation of various specific functional foods. Moreover,
      because of their growth and metabolism, the final products are preserved for a
      certain time. Thus, growth dynamics of the lactic acid bacteria of the Fresco DVS
      1010 culture ( Lactococcus lactis spp. lactis, Lactococcus lactis spp. cremoris,
      Streptococcus salivarius spp. thermophilus) during liquid-state fermentation of
      soya mashes and pH values within the process were analyzed in this study.
      Although milk is the most typical growth medium for the lactic acid bacteria,
      presumable viable counts of Fresco culture reached levels 109 CFU ml-1 after 8 h,
      representing 2-3 log increase in comparison to initial state (specific growth
      rates ranged from 1.06 to 1.64 h-1). After 21 days of storage period, the pH
      levels in the products were reduced to 4.50-4.70, representing a decrease of
      about 1.5-1.7 units. All prepared soybean products contained detectable amounts
      of raffinose-series oligosaccharides (0.25-0.68 g per 100 g) that were reduced in
      average by about 30.5% during period of 21 days.

PMID- 30286624
TI  - The safety of bevazicumab for the treatment of ovarian cancer.
AB  - INTRODUCTION: The safety profile of bevacizumab (BV) remains a challenging issue,
      in particular its role in fragile OC patients. Areas covered: In this literature
      review, we have analyzed safety data from Phase III trials evaluating the
      combination of BV plus standard chemotherapy in advanced or recurrent OC
      patients. In particular, our review aimed at clarifying the impact of the drug on
      fragile patients, and the correlation between BV and postoperative complications
      after cytoreductive surgery. Expert opinion: The addition of BV to standard
      chemotherapy regimens may cause unexpected side effects such as hypertension or
      proteinuria in up to 10% of women receiving the drug. BV administration is not
      associated with increase postoperative complications after cytoreductive surgery.
      Artero-venous thromboembolism and gastrointestinal perforation/fistula occurring
      in around 3% of OC patients treated with BV represent life-threatening events
      always requiring drug suspension. A closer monitoring is required in selected
      groups of women including: women with inflammatory bowel disease, or uncontrolled
      hypertension. Age itself is not a major contraindication, but older women should
      be carefully evaluated prior to start the drug. Finally, BV maintenance therapy
      should not be prematurely stopped due to minor events, since drug suspension may
      reduce survival.

PMID- 30286625
TI  - Ten-Year Follow-Up of Off-Pump and On-Pump Multivessel Coronary Artery Bypass
      Grafting: MASS III.
AB  - It was a randomized trial, and 308 patients undergoing revascularization were
      randomly assigned: 155 to off-pump coronary artery bypass (OPCAB) and 153 to on
      pump coronary artery bypass (ONCAB). End points were freedom from death,
      myocardial infarction, revascularization, and cerebrovascular accidents. The
      rates for 10-year, event-free survival for ONCAB versus OPCAB were 69.6% and 64%,
      (hazard ratio [HR]: 0.88; 95% confidence interval [CI] 0.86-1.02; P = .41),
      respectively. Adjusted Cox proportional hazard ratio was similar (HR: 0.92; 95%
      CI 0.61-1.38, P = .68). A difference occurred between the duration of OPCAB and
      ONCAB, respectively (4.9 +/- 1.5 vs 6.6 +/- 1.1 h, P < .001). Statistical
      differences occurred between OPCAB and ONCAB in the length of intensive care unit
      (ICU) stay (20 +/- 2.5 vs 48 +/- 10 hours, P < .001), time to extubation (5.5 +/-
      4.2 vs 10.2 +/- 3.5 hours, P < .001), hospital stay (6.7 +/- 1.4 vs 9.2 +/- 1.3
      days, P < .001), higher incidence of atrial fibrillation (AF; 33 vs 5 patients, P
      < .001), and blood requirements (46 vs 64 patients, P < .001). Grafts per patient
      was higher in ONCAB (3.15 vs 2.55 grafts, P < .001). No difference existed
      between the groups in primary composite end points at 10-year follow-up. Although
      OPCAB surgery was related to a lower number of grafts and higher incidence of AF,
      it had no effects related to long-term outcomes.

PMID- 30286626
TI  - Acupuncture Application in Chronic Kidney Disease and its Potential Mechanisms.
AB  - Chronic kidney disease (CKD) is an increasing major public health problem
      worldwide. The number of CKD patients on hemodialysis is growing rapidly as well.
      Acupuncture technique is one of the traditional Chinese medicine methods and has
      been used in a variety of diseases. Nowadays, the clinical application of
      acupuncture technique for CKD patients has become the focus for its effectiveness
      and security. In this paper, we will review the therapeutic effects and
      mechanisms of different acupuncture techniques for CKD patients. In patients with
      CKD, acupuncture improves renal function, reduces proteinuria, controls
      hypertension, corrects anemia, relieves pain, and controls many hemodialysis
      related complications such as uremic pruritus, insomnia and fatigue. The
      mechanisms are related to the regulation of sympathetic nerve and the activation
      of bioactive chemicals. In conclusion, acupuncture is proved to be beneficial for
      CKD patients. More research, however, is needed to verify the potential
      mechanisms.

PMID- 30286627
TI  - Comparative efficacy of brigatinib versus ceritinib and alectinib in patients
      with crizotinib-refractory anaplastic lymphoma kinase-positive non-small cell
      lung cancer.
AB  - OBJECTIVE: Brigatinib, ceritinib, and alectinib are approved to treat crizotinib
      refractory anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer
      (NSCLC), but no trial has compared them head-to-head. A matching-adjusted
      indirect comparison (MAIC) was conducted to estimate the relative efficacy of
      these agents in the crizotinib-refractory setting. METHODS: MAIC is a propensity
      score-type method that adjusts for differences in baseline characteristics
      between trials to estimate relative efficacy. Analyses were based on patient
      level data from the ALTA trial for brigatinib and published summary-level trial
      data from ASCEND-1 and ASCEND-2 for ceritinib and NP28761 and NP28673 for
      alectinib. Objective response rate (ORR), progression-free survival (PFS), and
      overall survival (OS) were compared. RESULTS: After matching, all key baseline
      characteristics were balanced between trials. Compared with ceritinib, brigatinib
      was associated with longer PFS (ASCEND-1: median 15.7 vs 6.9 months, hazard ratio
      (HR) [95% confidence interval] = 0.38 [0.26-0.57]; ASCEND-2: median = 18.3 vs 7.2
      months, HR = 0.33 [0.20-0.56]) and OS (ASCEND-1: not available; ASCEND-2: median
      27.6 vs 14.9 months, HR = 0.33 [0.17-0.63]). Versus alectinib, brigatinib was
      associated with longer PFS (NP28761: median = 17.6 vs 8.2 months, HR = 0.56 [0.36
      0.86]; NP28673: median = 17.6 vs 8.9 months, HR = 0.61 [0.40-0.93]); results for
      OS were inconclusive (NP28761: median = 27.6 vs 22.7 months, HR = 0.70 [0.42
      1.16]; NP28673: median = 27.6 vs 26.0 months, HR = 0.66 [0.39-1.09]). ORR was
      similar. CONCLUSION: In crizotinib-refractory ALK + NSCLC patients, relative
      efficacy estimates suggest brigatinib may have prolonged PFS and OS vs ceritinib
      and prolonged PFS vs alectinib.

PMID- 30286628
TI  - A randomised controlled trial of excision versus invagination in the management
      of indirect inguinal hernial sac.
AB  - INTRODUCTION: Lichtenstein tension-free mesh hernioplasty of primary inguinal
      hernia is currently considered as the preferred method for the plastic
      reconstruction of inguinal hernia by the majority of surgeons. Several studies
      have examined the best way to manage the hernial sac in this surgery, but no
      consensus has been reached. This study was designed to compare the effects of
      excision of sac and invagination of sac on post-operative outcomes. METHODS AND
      METHODS: This prospective randomised study included a total of 70 patients with
      primary unilateral uncomplicated indirect inguinal hernia. Group A (35 patients)
      underwent high dissection and invagination of the hernial sac and group B (35
      patients) underwent high ligation and excision of the hernial sac. The repair of
      the posterior wall of the inguinal canal was done according to Lichtenstein
      tension-free technique. The primary outcome of this study was postoperative pain
      and secondary outcomes were wound infection, chronic sepsis, sinus formation,
      persistent pain, testicular atrophy and recurrence during the one-year follow-up
      period. RESULTS: There was a significant difference (P < 0.01) in pain
      experienced by the patients in the immediate post-operative period between the
      two groups; group A experienced less postoperative pain than group B. There was
      no significant difference in incidence of infection between the groups.
      CONCLUSIONS: Invagination of the sac results in less postoperative pain compared
      with excision, with no significant difference in other postoperative outcomes.

PMID- 30286629
TI  - Indirect reduction screws: a technique to aid reduction in intramedullary
      nailing.

PMID- 30286630
TI  - Informed consent: the view from the trenches.
AB  - We review some of the recent literature on consent for surgical procedures and
      suggest a scheme for obtaining surgical consent.

PMID- 30286631
TI  - A technique to localise occult breast lesions detected mammographically: the
      hybrid of wire localisation and sonography guided patent blue marking.

PMID- 30286633
TI  - Percutaneous caecostomy for the management of closed loop large bowel
      obstruction: A delayed complication of severe gallstone pancreatitis.
AB  - Colonic complications following pancreatitis are unusual events ranging from 1%
      to 15%. In a patient with a hostile abdomen and multiple previous laparotomies,
      surgical management of a closed-loop large-bowel obstruction risks significant
      morbidity and mortality for the patient, necessitating other strategies for
      management. Caecostomy in the management of large bowel obstruction is an often
      forgotten weapon in the general surgeons' armoury.

PMID- 30286632
TI  - Nasal obstruction secondary to an inverted midline supernumerary tooth.
AB  - We present the case of a 36-year-old man who presented with left-sided nasal
      obstruction and facial pain. Clinical examination and computed tomography
      revealed an inverted midline supernumerary tooth buckling and deviating the nasal
      septum to the left. Full surgical resection of the tooth was achieved through a
      minimally invasive endoscopic septoplasty with full resolution of symptoms. There
      is little precedent within the literature to guide our management in this case
      and therefore we offer a successful surgical treatment strategy.

PMID- 30286635
TI  - Technical tip when performing a dynamic hip screw in a below-knee amputee: novel
      use of foot holder.

PMID- 30286634
TI  - A review of endovascular treatment of thoracic aorta disease.
AB  - INTRODUCTION: The development of thoracic endovascular aortic repair has altered
      the approach and reduced the risk of treating the majority of descending thoracic
      aortic conditions. Primarily developed for the exclusion of thoracic aortic
      aneurysms, it is now used in place of open repair surgery for most descending
      thoracic aortic diseases, and has also been used to treat aortic arch diseases in
      selected cases. METHODS: A literature search was conducted of Medline and Embase
      databases from January 2007 to February 2017, using the key words 'aortic
      disease', 'thoracic aorta' and 'endovascular repair'; 205 articles were
      identified, of which 25 studies were selected for review based on their
      relevance. FINDINGS: The key findings of the indications, techniques, outcomes,
      complications and comparisons with open surgical repair were extracted from the
      published studies and are summarised in this review. Thoracic endovascular aortic
      repair is the preferred choice of intervention for patients with descending
      thoracic aortic disease. With time, it has improved to be safer and has the
      potential to expand aortic treatment choices in future.

PMID- 30286636
TI  - Excision with primary midline closure compared with Limberg flap in the treatment
      of sacrococcygeal pilonidal disease: a randomised clinical trial.
AB  - BACKGROUND: Although several surgical techniques for treatment of sacrococcygeal
      pilonidal sinus (SPND) have been described, there is no consensus on the optimal
      surgical procedure. In this study we compared excision with primary closure and
      Limberg flap in the treatment of SPND. METHODS: This was a prospective randomised
      clinical trial in patients with SPND who were randomly allocated to one of two
      groups: group I (excision and primary closure) and group II (Limberg flap
      technique). The primary outcome of the trial was recurrence of SPND whereas
      postoperative complications, return to work and cosmetic results were the
      secondary outcomes. RESULTS: Sixty patients were included, with a mean age of
      24.1 years and mean body mass index (BMI) of 26.8 kg/m2. Group 1 had
      significantly shorter operation time than group II. Both groups had similar
      hospital stay and comparable complication rates (43.3% vs 30%; P = 0.4). Group I
      had significantly higher recurrence rate (20% vs 0; P < 0.02) and significantly
      better cosmetic satisfaction score than group II. Being hairy (P = 0.04),
      positive family history (P = 0.03), diabetes mellitus (P = 0.005) and history of
      previous surgery for SPND (P = 0.01) were the significant predictors for
      recurrence. CONCLUSIONS: The Limberg flap is an effective technique for the
      treatment of SPND with very low recurrence rate and comparable complication rate
      and hospital stay to excision and primary closure. Excision and primary closure
      offered the advantages of quicker healing time, earlier resumption of daily
      activities, better cosmetic results, which may render it more suitable for
      patients with low risk for recurrence.

PMID- 30286637
TI  - Novel use of air in laser ablation of bladder transitional cell carcinoma.

PMID- 30286638
TI  - Emergent thyroidectomy with sternotomy due to acute respiratory failure with
      severe thyroid storm.
AB  - Huge cervical and mediastinal masses may lead to acute respiratory failure caused
      by laryngotracheal compression and airway obstruction. Thyroid storm is also a
      life-threatening endocrine emergency originating almost exclusively from
      uncontrolled Graves' disease. We report a case of a 42-year-old man with acute
      upper airway obstruction and tachycardia from progressive swelling of a giant
      thyroid, in conjunction with thyroid storm resulting from uncontrolled Graves'
      disease. Fibreoptic-assisted nasal intubation was performed while the patient was
      awake, immediately followed by emergency total thyroidectomy via a cervical and
      sternal approach. The patient had an uneventful postoperative course and
      recovered well. Respiratory failure due to swelling of a giant thyroid is a life
      threatening condition and should be treated immediately with endotracheal
      intubation while the patient is awake following emergent total thyroidectomy,
      even with a sternotomy.

PMID- 30286639
TI  - A novel method of 'hands-free' laparoscopic retraction.

PMID- 30286640
TI  - Gastric tube volvulus following an Ivor-Lewis esophagectomy.
AB  - Gastric tube conduit is the method of choice for restoring continuity of the
      digestive track after a partial or total esophagectomy. Redundant gastric conduit
      (i.e. an elongated, floppy conduit) is a rare cause of dysphagia in patients with
      long survival. Gastric tube volvulus is exceedingly rare with only three cases
      described in the literature. We present the diagnostic and therapeutic course of
      a 57-year-old man who presented to our department with gastric tube volvulus 32
      months after an Ivor-Lewis esophagectomy. Diagnosis was made with computed
      tomography and volvulus was reduced endoscopically. To the best of our knowledge,
      this is only the fourth case of gastric tube volvulus described in the English
      literature. This rare situation might be a consequence of a redundant gastric
      tube. Endoscopic volvulus decompression was successful in our case.

PMID- 30286641
TI  - Delayed presentation of iatrogenic ventriculoperitoneal shunt transection
      following laparoscopic weight loss surgery in a patient with idiopathic
      intracranial hypertension.
AB  - Idiopathic intracranial hypertension is strongly associated with central obesity
      and consequential raised intra-abdominal pressure. If left untreated it poses
      significant risk to vision and can eventually cause blindness. Owing to its
      pathophysiology, this condition is managed by both medical and surgical
      specialities. When medical management fails neurosurgeons commonly treat
      idiopathic intracranial hypertension by permanent cerebrospinal fluid peritoneal
      shunting. Weight reduction surgery provides patients who are obese with a
      multitude of benefits and it is not uncommon for the general surgeon to be
      presented with a patient with idiopathic intracranial hypertension and a
      cerebrospinal fluid peritoneal shunt in place. This provides a potential
      challenging situation in weight-loss surgical procedures. We describe an
      interesting case where laparoscopic bariatric surgery resulted in transection of
      the abdominal catheter with a delayed presentation of recurrent symptoms and an
      abdominal cerebrospinal fluid collection in a patient with idiopathic
      intracranial hypertension. We discuss how this could be avoided and its
      management.

PMID- 30286642
TI  - Wooden spatula sinusitis following maxillary expansion surgery.
AB  - Sinusitis is a recognised rare complication of palatine expansion procedures and
      is usually caused by the presence of an oroantral fistula. We report the first
      case of unilateral sinusitis as a result of a retained foreign body (a wooden
      spatula) following a surgically assisted rapid palatine expansion procedure.

PMID- 30286643
TI  - A rare case of aortocaval fistula caused by type I endoleak after endovascular
      repair of abdominal aortic aneurysm.
AB  - In this rare case, an aortocaval fistula caused by a type I endoleak following
      endovascular repair of an abdominal aortic aneurysm (AAA) in a 75-year-old man
      was treated successfully with repeat endovascular aortic stent implantation.
      Postoperatively, the patient's symptoms were significantly improved, and
      angiography at nine months showed no endoleak in the aneurysm and no occlusion in
      the compressed inferior vena cava. Endovascular interventional surgery may be a
      safe and effective approach to treating AAA with concomitant aortocaval fistula.
      The use of covered stents to isolate the fistula from the venous side may not be
      necessary in the first stage of surgery.

PMID- 30286644
TI  - Will we ever cure nasal polyps?
AB  - BACKGROUND: Nasal polyposis is a benign hyperplastic growth of nasal mucosa.
      There is a paucity of evidence on the prevalence and incidence of nasal
      polyposis. Although nasal polyps can be asymptomatic, they can cause a spectrum
      of nasal problems including nasal obstruction, rhinorrhoea, nasal congestion,
      anosmia resulting in ageusia. Nasal polyps are mostly associated with chronic
      rhinosinusitis, The current management of chronic rhinosinusitis with nasal
      polyps is controversial and is not curative. METHODS: A Medline search was
      conducted, using the keywords 'rhinosinusitis', 'sinusitis', 'classification' and
      ''aetiology. FINDINGS: The current treatment of nasal polyposis in chronic
      rhinosinusitis with nasal polyps is still challenging. Emerging research through
      endotypes profiling aims to better understand the complexities of this
      heterogeneous disease to personalise treatment and provide a cure. Randomised
      controlled trials aim to provide robust evidence for current management options.

PMID- 30286645
TI  - Suture choice to reduce occurrence of surgical site infection, hernia, wound
      dehiscence and sinus/fistula: a network meta-analysis.
AB  - BACKGROUND: There are many options and little guiding evidence when choosing
      suture types with which to close the abdominal wall fascia. This network meta
      analysis investigated the effect of suture materials on surgical site infection,
      hernia, wound dehiscence and sinus/fistula occurrence after abdominal surgery.
      The aim was to provide clarity on whether previous recommendations on suture
      choice could be followed with confidence. METHODS AND METHODS: In February 2017,
      the Cochrane Central Register of Controlled Trials, Medline, EMBASE and Science
      Citation Index Expanded were searched for randomised controlled trials
      investigating the effect of suture choice on these four complications in closing
      the abdomen. A reference search of identified trials was performed. Prisma
      guidelines and the Cochrane risk of bias tool were followed in the data
      extraction and synthesis. Two review authors screened titles and abstracts of
      trials identified. A random effect model was used for the surgical site infection
      network based on the deviance information criterion statistics. RESULTS: Thirty
      one trials were included (11,533 participants). No suture material reached the
      predetermined 90% probability threshold for determination of 'best treatment' for
      any outcome. Pairwise comparisons largely showed no differences between suture
      types for all outcomes measured. However, nylon demonstrated a reduction in the
      occurrence of incisional hernias with respect to two commonly used absorbable
      sutures: polyglycolic acid (odds ratio, OR 1.91; 95% confidence interval, CI,
      1.01-3.63) and polyglyconate (OR 2.18; 95% CI 1.17-4.07). CONCLUSIONS: No suture
      type can be considered the 'best treatment' for the prevention of surgical site
      infection, hernia, wound dehiscence and sinus/fistula occurrence.

PMID- 30286646
TI  - The diagnostic yield of computed tomography in the management of acute flank pain
      and the emergency intervention rate for a proven acute ureteric stone.
AB  - INTRODUCTION: The diagnostic and management pathways for patients presenting with
      acute flank pain are complex. Although computed tomography (CT) of the kidneys,
      ureters and bladder (KUB) is the gold standard investigation for urolithiasis,
      the multitude of differential diagnoses must also be considered in the context of
      long-term risk from ionising radiation. This study investigated the integrated
      role and diagnostic yield of non-contrast CT in cases of acute flank pain.
      METHODS: A retrospective cohort study was undertaken of 1,442 consecutive
      patients investigated with CT KUB between March 2013 and February 2015. The
      primary outcome was diagnostic yield of CT with secondary outcomes being
      predictors of need for urological intervention. RESULTS: A cause for acute flank
      pain was identified in 717 patients (50%), there was an incidental finding in 389
      patients (27%) and normal imaging was reported in 336 patients (23%). A diagnosis
      was more commonly made in male than in female patients (70% vs 40%) and with
      increasing age (46% in patients aged <30 years, 56% in those aged 30-49 years and
      63% in those aged >=50 years). The overall rate for an ipsilateral urinary tract
      stone was 41%. Factors strongly associated with emergency intervention included
      stone size >10mm (odds ratio [OR]: 11.7, 95% confidence interval [CI]: 3.3-42.7),
      stones located at the pelviureteric junction (OR: 7.8, 95% CI: 2.6-22.9), C
      reactive protein >50mg/l and <=100mg/l (OR: 15.2, 95% CI: 5.1-45.3), and
      estimated glomerular filtration rate <=30ml/min (OR: 5.8, 95% CI: 1.5-21.8).
      CONCLUSIONS: This contemporary study identifies age and sex as independent
      variables affecting the diagnostic yield of CT KUB in cases of acute flank pain,
      and highlights factors associated with a need for emergency intervention in
      proven ureteric stones.

PMID- 30286647
TI  - Percutaneous cholecystostomy... why, when, what next? A systematic review of past
      decade.
AB  - INTRODUCTION: Percutaneous cholecystostomy tube drainage has played a vital role
      in management of cholecystitis in patients where surgery is not appropriate.
      However, management differs from unit to unit and even between different
      consultants in the same unit. We conducted this systematic review to understand
      which of these resulted in the best patient outcomes. METHODS: We conducted a
      systematic review using the PubMed database for publication between January 2006
      to December 2016. Keyword variants of 'cholecystostomy' and 'cholecystitis' were
      combined to identify potential relevant papers for inclusion. FINDINGS: We
      identified 46 studies comprising a total of 312,085 patients from 20 different
      countries. These papers were reviewed, critically appraised and summarised in
      table format. Percutaneous cholecystostomy tube drainage is an important
      treatment modality with an excellent safety profile. It has been used
      successfully both as a definitive procedure and as a bridge to surgery. There
      continues to be great variation, however, when it comes to the indications,
      timing and management of these drains. As far as we are aware, this is the only
      systematic review to cover the past 10 years. It provides a much-needed update,
      considering all the technological development and new treatment options in
      laparoscopic surgery and interventional radiology.

PMID- 30286648
TI  - A prospective clinical, cost and environmental analysis of a clinician-led
      virtual urology clinic.
AB  - INTRODUCTION: Minimally invasive parathyroidectomy (MIP) for primary
      hyperparathyroidism is dependent upon accurate prediction of single-gland disease
      on the basis of preoperative imaging and biochemistry. The aims of this study
      were to validate currently available predictive models of single-gland disease in
      two UK cohorts and to determine if these models can facilitate MIP. MATERIAL AND
      METHODS: We collected data prospectively from our weekly follow-up virtual clinic
      over a continuous four-month period between July and September 2017. RESULTS: In
      total, we reviewed 409 patients. Following virtual clinic consultation, 68.5% of
      our patients were discharged from further follow-up. The majority of our patients
      (male 57.7%, female 55.5%) were of working age. The satisfaction scores were
      high, at 90.1%, and there were no reported adverse events as a result of using
      the virtual clinic. Our calculated cost savings were L18,744, with a predicted 12
      month cost saving of L56,232. The creation of additional face-to-face clinic
      capacity has created an estimated 12-month increase in tariff generation for our
      unit of L72,072. In total, 4623 travel miles were avoided by patients using the
      virtual clinic, with an estimated avoided carbon footprint of 0.35-1.45 metric
      tonnes of CO2e, depending on mode of transport. Our predicted 12-month avoided
      carbon footprint is 1.04-4.04 metric tonnes of CO2e. CONCLUSIONS: Our virtual
      clinic model has demonstrated a trifecta of positive outcomes, namely, clinical,
      financial and environmental benefits. The environmental importance and benefits
      of a virtual clinic should be promoted as a social enterprise value when engaging
      stakeholders in setting up such a urological service. We propose the adoption of
      our virtual clinic model in those urological units considering this method of
      telemedicine.

PMID- 30286649
TI  - Logistic regression model to predict acute uncomplicated and complicated
      appendicitis.
AB  - INTRODUCTION: While patients with acute uncomplicated appendicitis may be treated
      conservatively, those who suffer from complicated appendicitis require surgery.
      We describe a logistic regression equation to calculate the likelihood of acute
      uncomplicated appendicitis and complicated appendicitis in patients presenting to
      the emergency department with suspected acute appendicitis. MATERIALS AND
      METHODS: A cohort of 895 patients who underwent appendicectomy were analysed
      retrospectively. Depending on the final histology, patients were divided into
      three groups; normal appendix, acute uncomplicated appendicitis and complicated
      appendicitis. Normal appendix was considered the reference category, while acute
      uncomplicated appendicitis and complicated appendicitis were the nominal
      categories. Multivariate and univariate regression models were undertaken to
      detect independent variables with significant odds ratio that can predict acute
      uncomplicated appendicitis and complicated appendicitis. Subsequently, a logistic
      regression equation was generated to produce the likelihood acute uncomplicated
      appendicitis and complicated appendicitis. RESULTS: Pathological diagnosis of
      normal appendix, acute uncomplicated appendicitis and complicated appendicitis
      was identified in 188 (21%), 525 (59%) and 182 patients (20%), respectively. The
      odds ratio from a univariate analysis to predict complicated appendicitis for
      age, female gender, log2 white cell count, log2 C-reactive protein and log2
      bilirubin were 1.02 (95% confidence interval, CI, 1.01, 1.04), 2.37 (95% CI 1.51,
      3.70), 9.74 (95% CI 5.41, 17.5), 1.57 (95% CI 1.40, 1.74), 2.08 (95% CI 1.56,
      2.76), respectively. For the same variable, similar odds ratios were demonstrated
      in a multivariate analysis to predict complicated appendicitis and univariate and
      multivariate analysis to predict acute uncomplicated appendicitis. CONCLUSIONS:
      The likelihood of acute uncomplicated appendicitis and complicated appendicitis
      can be calculated by using the reported predictive equations integrated into a
      web application at www.appendistat.com. This will enable clinicians to determine
      the probability of appendicitis and the need for urgent surgery in case of
      complicated appendicitis. ACKNOWLEDGEMENTS: This work would have not been
      completed without the help of: Clarissa Y. M. Carvallho, Consultant Anaesthetist
      at Guy's and St Thomas's Hospital; Bried O'Brien, the Head of Urgent Care
      Transformation at University College London Hospital; and Guang's Wu, Web
      Application Developer. Their contribution to building the web application allowed
      this work to materialise into clinical use to benefit patients.

PMID- 30286650
TI  - Does the Intercollegiate Membership of the Royal College of Surgeons (MRCS)
      examination predict 'on-the-job' performance during UK higher specialty surgical
      training?
AB  - INTRODUCTION: The Intercollegiate Membership of the Royal College of Surgeons
      (MRCS) is a mandatory examination to enter higher surgical specialty training in
      the UK. It is designed to help to ensure that successful candidates are competent
      to practice as higher surgical trainees. The annual review of competence
      progression (ARCP) assesses trainees' competence to progress to the next level of
      training and can be interpreted as a measure of 'on-the-job' performance. We
      investigated the relationship between MRCS performance and ARCP outcomes.
      MATERIALS AND METHODS: All UK medical graduates who passed MRCS (Parts A and B)
      from 2007 to 2016 were included. MRCS scores, attempts and sociodemographics for
      each candidate were crosslinked with ARCP outcomes (satisfactory, unsatisfactory
      and insufficient evidence). Multinomial logistic regression was used to identify
      potential independent predictors of ARCP outcomes. RESULTS: A total of 2570
      trainees underwent 11,064 ARCPs; 1589 (61.8%) had only satisfactory outcomes
      recorded throughout training; 510 (19.9%) had at least one unsatisfactory
      outcome; and 471 (18.3%) supplied insufficient evidence. After adjusting for age,
      gender, first language and Part A performance, ethnicity (non-white vs white, OR
      1.36, 95% CI 1.08 to 1.71), Part B passing score (OR 0.98, 95% CI 0.98 to 1.00)
      and number of attempts at Part B (two or more attempts vs one attempt, OR 1.50,
      95% CI 1.16 to 1.94) were found to be independent predictors of an unsatisfactory
      ARCP outcome. CONCLUSIONS: This is the first study to identify predictors of ARCP
      outcomes during higher surgical specialty training in the UK and provides further
      evidence of the predictive validity of the MRCS examination.

PMID- 30286651
TI  - Surgery for Cushing's disease in pregnancy: our experience and a literature
      review.
AB  - Cushing's syndrome in pregnancy is a rare phenomenon and there is limited
      literature on its management. Cushing's disease in pregnancy is even less common
      and there is little guidance to help in the treatment for this patient group.
      Diagnosis of Cushing's syndrome in pregnancy is often delayed due to overlap of
      symptoms. In addition, there are no validated diagnostic tests or parameters
      documented. We present a case of a 30-year-old woman presenting to the antenatal
      clinic at 13 weeks of pregnancy with high suspicion of Cushing's disease. Her 21
      week fetal scan showed a congenital diaphragmatic hernia and she underwent
      pituitary magnetic resonance imaging, which confirm Cushing's disease. She
      successfully underwent transsphenoidal adenomectomy with histology confirming a
      corticotroph adenoma. Tests following transsphenoidal surgery confirmed remission
      of Cushing's disease and she underwent an emergency caesarean section at 38
      weeks. Unfortunately, her baby died from complications associated with the
      congenital abnormality 36 hours after birth. The patient remains in remission
      following delivery. To date, there have been no reported cases of congenital
      diaphragmatic hernia associated with Cushing's disease in pregnancy. In addition,
      we believe that this is only the eighth reported patient to have undergone
      successful transsphenoidal surgery for Cushing's disease in pregnancy.

PMID- 30286652
TI  - A selective non-operative approach to thoracic stab wounds is safe and cost
      effective - a South African experience.
AB  - INTRODUCTION: Penetrating thoracic trauma is common and costly. Injuries are
      frequently and selectively amenable to non-operative management. Our selective
      approach to penetrating thoracic trauma is reviewed and the effectiveness of our
      clinical algorithms confirmed. Additionally, a basic cost analysis was undertaken
      to evaluate the financial impact of a selective nonoperative management approach
      to penetrating thoracic trauma. MATERIALS AND METHODS: The Pietermaritzburg
      Metropolitan Trauma Services electronic regional trauma registry hybrid
      electronic medical records were reviewed, highlighted all penetrating thoracic
      traumas. A micro-cost analysis estimated expenses for active observation, tube
      thoracostomy for isolated pneumothorax greater than 2 cm and tube thoracostomy
      for haemothorax. Routine thoracic computed tomography does not form part of these
      algorithms. RESULTS: Isolated thoracic stab wounds occurred in 589 patients.
      Eighty per cent (472 cases) were successfully managed nonoperatively. Micro
      costing shows that active observation costs 4,370 ZAR (L270), tube thoracostomy
      for isolated pneumothorax costs 6,630 ZAR (L400) and tube thoracostomy for
      haemothorax costs 21,850 ZAR (L1,310). DISCUSSION: Penetrating thoracic trauma
      places a striking financial burden on our limited resources. Diligent and serial
      clinical assessments, alongside basic radiology and stringent management
      criteria, can accurately stratify patients to correct clinical algorithms.
      CONCLUSION: Selective nonoperative management for penetrating thoracic trauma is
      safe and effective. Routine thoracic computed tomography is unnecessary in all
      patients with isolated thoracic stab wounds, which can be reserved for a select
      group who are identifiable clinically. Routine thoracic computed tomography would
      not be financially prudent across Pietermaritzburg Metropolitan Trauma Services.
      Government action is required to reduce the overall incidence of such trauma to
      save resources and patients.

PMID- 30286653
TI  - Are on-the-day group and save samples required for elective shoulder, hip and
      knee arthroplasties?
AB  - INTRODUCTION: Historically, patients undergoing an elective hip, knee or shoulder
      arthroplasty regularly required blood transfusions. Improved surgical techniques
      and perioperative optimisation have significantly decreased the requirement for
      blood transfusions. Currently, our patients have two group and save samples
      taken: one six weeks preoperatively and one on admission. This study aims to
      determine whether a second group and save is required prior to primary elective
      hip, knee or shoulder arthroplasty. METHODS: All cases of elective arthroplasty
      from a single centre were retrospectively analysed over a 16-month period. Each
      case was reviewed to determine those who had a group and save at preassessment,
      group and save at the time of the operation and the timing and number of blood
      products transfused. RESULTS: A total of 711 elective arthroplasty procedures
      were completed with 48 patients requiring a transfusion during their admission.
      9.9% of hip arthroplasty patients, 3.8% of knee arthroplasty patients and 4.9% of
      shoulder arthroplasty patients required a transfusion. The majority of the
      transfusions occurred at least 24 hours postoperatively with 0.84% of patients
      requiring an intraoperative transfusion. DISCUSSION: The vast majority of
      transfusions were delivered more than 24 hours following the procedure,
      demonstrating that routinely cross-matched blood products are superfluous to
      requirements. It is our suggestion that a formal group and save be completed only
      if the need for a blood transfusion is formally established, leading to a
      significant cost saving, a reduction in clinical work load and patients having to
      undergo fewer procedures.

PMID- 30286654
TI  - The rare case of an extraperitoneal ureteral herniation into the inguinal canal
      of a 12-year-old boy.
AB  - Ureteric herniation into the inguinal canal is a rare condition in adults and
      even more so in the paediatric population. These hernia types can be categorised
      as paraperitoneal or extraperitoneal. The former are the only varieties
      encountered in the paediatric literature, where patients are generally infants,
      while the latter phenomenon is seen in 20% of ureteric herniations in adults. We
      present a case of an extraperitoneal ureteric herniation into the inguinal canal
      in a 12-year-old boy with previous surgery for cloacal exstrophy, analyse the
      existing literature on the condition and make the speculation that the
      extraperitoneal variety is an adult variant seen in this child because of
      weakness in the surrounding structures as a result of previous surgery.

PMID- 30286655
TI  - Minimal access perineal urethrostomy using percutaneous nephrolithotomy skills to
      complete holmium laser enucleation of the prostate.

PMID- 30286656
TI  - 30-day complication rates and patient-reported outcomes following day case
      primary lumbar microdiscectomy in a regional NHS spinal centre.
AB  - INTRODUCTION: Advances in surgical and anaesthesia technique have reduced length
      of stay for lumbar discectomy. Current evidence suggests that daycase surgery is
      associated with improved patient satisfaction, faster recovery, reduced infection
      rates and financial savings. We present our microdiscectomy daycase protocol,
      together with 30-day postoperative complication rates and patient reported
      outcomes in an NHS setting. METHODS AND METHODS: We retrospectively studied all
      patients that met a locally agreed daycase protocol for lumbar microdiscectomy
      and were operated upon and discharged on the same calendar day between 1 March
      2013 and 31 December 2015. RESULTS: A total of 134 patients underwent primary
      daycase microdiscectomy (70 males, 64 females). The cohort had a mean age of 41
      years (range 16-82 years). Some 96% (n = 129) were single-level procedures, 93%
      were unilateral (n = 125) and 81% (n = 109) took place at either L4/L5 or L5/S1.
      All patients were discharged on the same day as admission and operation. Four
      patients re-presented to hospital within 30 days and three were discharged from
      the emergency department within four hours following a clinical review. One
      patient required an inpatient stay for a washout of a superficial postoperative
      infection. Significant improvements (P < 0.05) were found postoperatively for
      back pain and leg pain on self-reported visual analogue scores and Oswestry
      Disability Index. CONCLUSION: In this study, we present a safe and effective
      protocol for day case lumbar microdiscectomy. Our 30-day postoperative
      complication rate of under 1% is comparable to that of traditional inpatient
      primary lumbar microdiscectomy. Patient-reported outcome measures revealed
      significant improvement in both pain and functional scores.

PMID- 30286657
TI  - Rhabdomyosarcoma of the middle ear cavity presenting with Horner's syndrome.
AB  - Rhabdomyosarcoma is a rare malignant tumour of striated muscle accounting for 3%
      of all primary soft tissue tumours of the middle ear cavity. We describe a unique
      case of a rhabdomyosarcoma of the middle ear cavity in a four-year-old boy,
      presenting as an otherwise asymptomatic ipsilateral Horner's syndrome. This case
      involved tumour erosion through the tensor tympani semicanal, accessing the
      carotid canal and the sympathetic plexus running through it. This child was
      treated successfully with chemotherapy and proton beam therapy, and remains
      disease free at six years of follow-up. This case highlights the importance of
      investigating patients with non-resolving ear infections, polyps or granulation
      tissue.

PMID- 30286658
TI  - Gastro-oesophageal fistula in an achalasia patient following myotomy as an
      unusual cause of heartburn.
AB  - We report a case of delayed presentation of a gastro-oesophageal fistula
      following a Heller myotomy and anterior fundoplication for achalasia in a 28-year
      old man. After a period of symptom resolution following initial operation,
      dysphagia and severe heartburn commenced temporarily, related to non-steroidal
      anti-inflammatory drug (NSAID) use. Endoscopy demonstrated a secondary opening in
      the lower oesophagus and a barium swallow showed an oesophageal fistula to the
      stomach. Currently, reasonable symptom control has been obtained on double dose
      pantoprazole. Barium study best demonstrated the abnormality. NSAIDs should
      possibly be avoided in cases of severe dysmotility of the oesophagus.

PMID- 30286659
TI  - Combined ultrasound and Sestamibi scintigraphy provides accurate preoperative
      localisation for patients with primary hyperparathyroidism.
AB  - INTRODUCTION: Minimally invasive parathyroidectomy has advantages over the
      traditional bilateral neck exploration for the surgical treatment of primary
      hyperparathyroidism. It requires accurate localisation of the parathyroid
      pathology prior to surgery. The best method of preoperative localisation in a
      district general hospital setting is not well understood. METHODS: All patients
      who underwent parathyroidectomy for primary hyperparathyroidism from 2008 to 2016
      were identified from a prospectively maintained database. Operative findings were
      correlated with radiological and histological results. Sensitivity and
      specificity of ultrasound, sestamibi scintigraphy and the two together were
      calculated for diagnostic precision and compared. RESULTS: One hundred and eighty
      four patients met the inclusion criteria, of whom 81.5% had a histological
      diagnosis of a parathyroid adenoma. Ultrasound had higher sensitivity than
      sestamibi scintigraphy. Used together, ultrasound and sestamibi scintigraphy
      performed better than either ultrasound or sestamibi scintigraphy alone (P<
      0.001). Twenty-two of 184 cases had no lesion located by either ultrasound or
      sestamibi scintigraphy preoperatively. Where neither ultrasound nor sestamibi
      scintigraphy located the lesion, additional computed tomography led to the
      excision of parathyroid pathology in one in ten patients. CONCLUSION: The
      combination of ultrasound and sestamibi scintigraphy provides the highest
      sensitivity of preoperative localisation. This approach led to a high success
      rate of minimally invasive parathyroidectomy. Where preoperative localisation is
      not achieved with ultrasound or sestamibi scintigraphy, computed tomography adds
      little additional benefit. In this setting other modalities of localisation such
      a selective venous sampling, intraoperative methylene blue or intraoperative
      parathyroid hormone levels could be considered.

PMID- 30286660
TI  - Computed tomography colonography: a new threat to the spleen?
AB  - We present a rare and previously undocumented potential complication of computed
      tomography (CT) colonography. CT colonography is a commonly performed
      investigation with a relatively low risk of complications. While splenic injury
      is a well-documented complication after colonoscopy, it has never been reported
      following CT colonography. A 64-year-old man presented with severe abdominal pain
      four hours after CT colonography. CT of his abdomen and pelvis revealed
      appearances consistent with intra-abdominal bleeding secondary to splenic injury.
      The patient immediately underwent an emergency laparotomy and splenectomy,
      revealing a grade III splenic capsular tear. Histological evaluation of splenic
      tissue showed normal morphology with no evidence of malignancy. While the
      aetiology of the patient's splenic injury remains uncertain, normal
      histopathology and the chronology of events represents an almost certain link to
      CT colonography.

PMID- 30286661
TI  - Speech pathology management of non-progressive dysarthria: a systematic review of
      the literature.
AB  - PURPOSE: The purpose of this study is to conduct a systematic review of
      interventions for the treatment of non-progressive dysarthria in adults.
      MATERIALS AND METHODS: Five electronic databases (PubMed, Embase, CINAHL,
      PSYCINFO, Cochrane Collaboration) were searched for all studies that described
      and evaluated treatment used for non-progressive dysarthria in adults. Studies
      were included if (1) participants were adults (18+ years) with a confirmed
      diagnosis of non-progressive dysarthria, (2) participants received intervention
      with pre-post outcome data, and (3) the article was published between 2006 and
      2017 (including early online publications). Data extracted included the number of
      participants; etiology; dysarthria type and severity; age; gender; presence of a
      control group; intervention tasks, frequency and duration; outcome measures; and
      conclusions. Data extraction was completed by a member of the research team
      independently and crosschecked by another team member. RESULTS: Of the 6728
      articles identified, 21 met the inclusion criteria. The predominant study design
      was a case study or case series. The methodological quality of the studies
      varied. Typically, the interventions included impairment-based and activity level
      tasks targeting conversation. Approximately half of the interventions adhered to
      a treatment manual. CONCLUSIONS: The evidence base to guide treatment for non
      progressive dysarthria is increasing, with interventions showing promise in
      results, participant numbers, and positive participant feedback. Implications for
      rehabilitation The evidence base to guide treatment for non-progressive
      dysarthria is increasing, but remains limited. The majority of evidence is of
      moderate methodological quality. The emergence of new research indicates that
      health professionals need to be continuously aware and critically appraise new
      literature in the area.

PMID- 30286662
TI  - Examination of burden of skeletal-related events in patients naive to denosumab
      and intravenous bisphosphonate therapy in bone metastases from solid tumors
      population.
AB  - OBJECTIVES: Skeletal-related events (SREs), i.e. pathologic fractures, spinal
      cord compression, surgery and radiation to bone, are serious skeletal
      complications that occur frequently in patients with bone metastases (BMs) from
      solid tumors (STs). Clinical guidelines recommend treatment with denosumab and
      intravenous bisphosphonates (IVBPs) to prevent SREs. However, therapy may be
      delayed by physicians due to perceived low risk of SREs or for other clinical
      reasons. This study estimated SRE incidence rates in treatment-naive (i.e. no
      denosumab or IVBPs) patients with BMs from STs in the US. METHODS: In this
      retrospective cohort study adult patients with diagnoses of BM and ST between 1
      January 2008 and 31 March 2015 were identified from MarketScan Databases. All
      patients had >=6 months of data before the first BM diagnosis date (index date)
      and were followed for >=6 months from the index date until the earliest of
      inpatient death, initiation of denosumab/IVBP therapy or end of data. The Kaplan
      Meier curve was used to estimate cumulative incidence of SREs. The incremental
      healthcare cost of SREs was estimated and compared to propensity score matched
      non-SRE patients. RESULTS: A total of 47,052 patients met the study criteria.
      Using the Kaplan-Meier method the cumulative incidences of SREs among treatment
      naive patients were 39.9% (95% confidence internal [CI]: 39.4-40.4), 46.3% (95%
      CI: 45.8-46.8), 52.5% (95% CI: 51.9-53.2) and 59.4% (95% CI: 58.6-60.3) by month
      6, 12, 24 and 48 post index date, respectively. The SRE group was associated with
      higher all-cause total healthcare cost per-patient-per-year compared to those
      without SREs ($168,277 vs. $101,020, p < .001). CONCLUSIONS: Almost half (46.3%)
      of the treatment-naive population with BMs from STs experience SREs within 1 year
      of the first BM diagnosis. SREs were associated with an average $67,257
      additional healthcare cost annually. Given the high SRE burden in these patients,
      early initiation of prophylactic therapy should be considered.

PMID- 30286663
TI  - Examining quality of care for individuals treated for mental health using the
      HEDIS mental health quality measures.
AB  - OBJECTIVE: This descriptive study examined the quality of care received by
      individuals with serious mental illness observed in clinical care using
      established Healthcare Effectiveness Data and Information Set (HEDIS) measures
      for individuals with serious mental illness. METHODS: Administrative claims
      (Medicaid, Medicare, and commercial) from a national health and well-being
      company were used to identify adults with schizophrenia or bipolar disorder.
      Performance rates for five HEDIS mental health quality measures were computed.
      Sub-group analyses examined each HEDIS measure by those who were medication
      adherent vs non-adherent, and by typical vs atypical antipsychotics. RESULTS:
      Eighty-nine percent of the Medicaid population received a diabetes screening (vs
      79% for national benchmark Medicaid rates), 81% (vs 69%) received monitoring for
      diabetes, 88% (vs 79%) received monitoring for cardiovascular disease, 63% (vs
      60%) were adherent with antipsychotic medication, and 34% (vs 61%) had a follow
      up visit with a mental health practitioner within 30 days of a discharge. The
      rates for individuals with Medicare coverage were similar or marginally higher
      than those reported for those with Medicaid coverage, while rates for the
      commercially insured population were lower than the other groups. CONCLUSIONS:
      Most (>65%) individuals with serious mental illness received the recommended
      screening and monitoring for diabetes and cardiovascular disease. Barriers to and
      reasons for lack of follow-up should be investigated to guide future
      interventions to improve follow-up after hospitalization for individuals with
      serious mental illness.

PMID- 30286664
TI  - Nationwide implementation of a national policy for evidence-based rehabilitation
      with focus on facilitating return to work: a survey of perceived use,
      facilitators, and barriers.
AB  - AIM: The aim is to assess whether the national policy for evidence-based
      rehabilitation with a focus on facilitating return-to-work is being implemented
      in health-care units in Sweden and which factors influence its implementation.
      METHODS: A survey design was used to investigate the implementation. Data were
      collected at county council management level (process leaders) and clinical level
      (clinicians in primary and secondary care) using web surveys. Data were analyzed
      using SPSS, presented as descriptive statistics. RESULTS: The response rate among
      the process leaders was 88% (n = 30). Twenty-eight percent reported that they had
      already introduced workplace interventions. A majority of the county councils'
      process leaders responded that the national policy was not clearly defined. The
      response rate among clinicians was 72% (n = 580). Few clinicians working with
      patients with common mental disorders or musculoskeletal disorders responded that
      they were in contact with a patient's employer, the occupational health services
      or the employment office (9-18%). Nearly, all clinicians responded that they
      often/always discuss work-related problems with their patients. CONCLUSIONS: The
      policy had been implemented or was to be implemented before the end of 2015. Lack
      of clearly stated goals, training, and guidelines were, however, barriers to
      implementation. Implications for rehabilitation Clinicians' positive attitudes
      and willingness to discuss workplace interventions with their patients were
      important facilitators related to the implementation of a nationwide policy for
      workplace interventions/rehabilitation. A lack of clearly stated goals, training,
      and guidelines were barriers related to the implementation. The development of
      evidence-based policies regarding rehabilitation and its implementation has to
      rely on very structured and clear descriptions of what to do, preferably with the
      help of practice guidelines. Nationwide implementation of rehabilitation policies
      has to allow time for preparation including communication of goals and competence
      assurance in a close collaboration with the end users, namely clinicians and
      patients. Abbreviations CBT Cognitive behavioral therapy CFIR Consolidated
      framework for implementation research CMD Common mental disorders IPT
      Interpersonal psychotherapy MMR Multimodal rehabilitation RG Rehabilitation
      guarantee RTW Return to work SPSS Statistical package for the social sciences.

PMID- 30286665
TI  - Partial tubal devascularisation: a novel procedure for tubal conservation in
      ectopic pregnancy.
AB  - Ectopic pregnancy is a serious condition that complicates 1-2% of pregnancies.
      Using surgical management is efficient, but may have an impact on future
      fertility. Although conservative tubal surgery has not been shown to have a
      significant advantage over a salpingectomy in terms of the future fertility
      potential, the conservative surgical techniques remain widely-utilised,
      particularly in the context of a contralateral diseased or absent tube. We hereby
      report a case series of a novel procedure to conserve the fallopian tube with the
      minimal risk of an incisional site bleeding through a partial segmental
      devascularisation. This technique seems to be an efficient method to minimise the
      intraoperative bleeding, limit the need for a blood transfusion, and yields a
      higher success rate of the procedure without jeopardising the blood supply and
      vitality of the tubes. Impact Statement What is already known on this subject?
      Conservative surgery has a significant value in women with a contralateral absent
      or diseased tube. However, a conservative management could be challenging due to
      the significant bleeding which can be encountered during the surgery. What the
      results of this study add? The partial devascularisation technique could achieve
      an adequate haemostasis by blocking the ascending blood supply only to the
      affected segment of the fallopian tube. What the implications are of these
      findings for clinical practice and/or further research? A partial
      devascularisation is a successful conservative surgical treatment option in most
      patients when the procedure is indicated.

PMID- 30286666
TI  - Chemotherapy for cervical cancer in pregnancy.

PMID- 30286667
TI  - Stress echocardiography in valvular heart disease.
AB  - INTRODUCTION: The management of patients with heart valve disease can be complex.
      Patients may have symptoms disproportionate to the severity or the severity may
      be unclear. In addition, the optimal timing of intervention in patients with
      severe disease may be controversial. Areas covered: This article examines the
      role of stress echocardiography for assessment of patients with low-flow, low
      gradient aortic stenosis, asymptomatic severe valve disease and patients where
      symptoms are discordant to the resting severity of valve disease. Expert
      commentary: Stress echocardiography helps clinicians determine the true severity
      of valve disease and may identify the cause of symptoms in patients with only
      mild/moderate disease. The data provided by stress echocardiography will help
      determine the appropriate management strategy and the correct timing of
      intervention.

PMID- 30286668
TI  - Dietary patterns, dietary intakes and the risk of type 2 diabetes: results from
      the Hefei Nutrition and Health Study.
AB  - A total of 1776 Chinese adults, aged 40-60 years, had been recruited to
      participate in the Hefei Nutrition and Health Study started in 2012. Three major
      dietary patterns were identified, "High-salt and high-fat", "Traditional Chinese"
      and "Western" dietary patterns. After adjusting for potential confounders, there
      is no significant difference in the effect of different dietary pattern quintiles
      on the risk of type 2 diabetes (T2D). However, compared with lowest quintile
      intakes, the adjusted odds ratio of T2D for highest quintile intakes of bread and
      noodle, rice noodle and coarse grain were 2.45 (95% CI: 1.17, 5.12), 0.34 (95%
      CI: 0.17, 0.92), 0.27 (95% CI: 0.14, 0.51), with corresponding p trend being
      .002, .375, .003, respectively. Our study suggests that high intakes of bread and
      noodle are significantly associated with increased risk of T2D, while high
      intakes of rice noodle and coarse grain are remarkably correlated with decreased
      risk of T2D.

PMID- 30286670
TI  - Pharmacological thrombolysis: the last choice for salvaging free flaps.
AB  - Microvascular free flap transfer has become a prevailing surgery with a failure
      rate of <5%. However, pedicle thrombosis occurs more frequently than indicated by
      the failure rate. This difference is due to the successful salvage of failing
      flaps. During exploration, thrombi are often encountered at anastomotic sites,
      whereas these causes could not explain vascular compromise in other patients.
      Thus, we hypothesized that thrombogenic processes might occur at remote sites,
      specifically within microvessels of the transferred flap. This study
      retrospectively evaluated 323 patients who underwent microvascular free flap
      transfer between March 2012 and October 2016 at Korea University Guro Hospital.
      All patients requiring emergency exploration within 7 days after surgery were
      retrospectively reviewed. Of patients, 15 required explorative surgery for
      suspected circulatory compromise. Eight were diagnosed with thrombosis at the
      perianastomotic site and salvaged in accordance with our protocol. There was no
      detectable thrombosis at the anastomotic site in seven patients, including one
      patient in whom thrombosis resolved with topical papaverine application and
      heparinization. The remaining six patients were diagnosed with intra-flap
      microthrombosis without discernable thrombosis at the anastomotic site. All
      patients were treated following our urokinase administration protocol and
      salvaged without complications. Possible external causes should first be
      evaluated when salvaging free flaps; in the absence of such evidence, urokinase
      administration may be utilized as a last resort. This study is the first report
      describing the effectiveness of pharmacological thrombolysis in resolving intra
      flap microthrombosis. Furthermore, a safe and efficient urokinase administration
      protocol is suggested for perianastomotic thrombosis and intra-flap
      microthrombosis.

PMID- 30286671
TI  - Adrenal infarction in the immediate postnatal period?.

PMID- 30286669
TI  - The insight of in vitro and in silico studies on cholinesterase inhibitors from
      the roots of Cimicifuga dahurica (Turcz.) Maxim.
AB  - Cholinesterases (ChEs) are enzymes that break down neurotransmitters associated
      with cognitive function and memory. We isolated cinnamic acids (1 and 2),
      indolinones (3 and 4), and cycloartane triterpenoid derivatives (5-19) from the
      roots of Cimicifuga dahurica (Turcz.) Maxim. by chromatography. These compounds
      were evaluated for their inhibitory activity toward ChEs. Compound 1 was
      determined to have an IC50 value of 16.7 +/- 1.9 MUM, and to act as a competitive
      inhibitor of acetylcholinesterase (AChE). Compounds 3, 4 and 14 were found to be
      noncompetitive with IC50 values of 13.8 +/- 1.5 and 6.5 +/- 2.5 MUM, and
      competitive with an IC50 value of 22.6 +/- 0.4 MUM, respectively, against
      butyrylcholinesterase (BuChE). Our molecular simulation suggested each key amino
      acid, Tyr337 of AChE and Asn228 of BuChE, which were corresponded with potential
      inhibitors 1, and 3 and 4, respectively. Compounds 1 and 4 were revealed to be
      promising compounds for inhibition of AChEs and BuChEs, respectively.

PMID- 30286672
TI  - Differences in the toxicity of cerium dioxide nanomaterials after inhalation can
      be explained by lung deposition, animal species and nanoforms.
AB  - Considerable differences in pulmonary responses have been observed in animals
      exposed to cerium dioxide nanoparticles via inhalation. These differences in
      pulmonary toxicity might be explained by differences in lung deposition, species
      susceptibility or physicochemical characteristics of the tested cerium dioxide
      nanoforms (i.e. same chemical substance, different size, shape, surface area or
      surface chemistry). In order to distinguish the relative importance of these
      different influencing factors, we performed a detailed analysis of the data from
      several inhalation studies with different exposure durations, species and
      nanoforms, namely published data on NM211 and NM212 (JRC repository), NanoAmor
      (commercially available) and our published and unpublished data on PROM (industry
      provided). Data were analyzed by comparing the observed pulmonary responses at
      similar external and internal dose levels. Our analyses confirm that rats are
      more sensitive to developing pulmonary inflammation compared to mice. The
      observed differences in responses do not result purely from differences in the
      delivered and retained doses (expressed in particle mass as well as surface
      area). In addition, the different nanoforms assessed showed differences in toxic
      potency likely due to differences in their physicochemical parameters. Primary
      particle and aggregate/agglomerate size distributions have a substantial impact
      on the deposited dose and consequently on the pulmonary response. However, in our
      evaluation size could not fully explain the difference observed in the analyzed
      studies indicating that the pulmonary response also depends on other
      physicochemical characteristics of the particles. It remains to be determined to
      what extent these findings can be generalized to other poorly soluble
      nanomaterials.

PMID- 30286673
TI  - Histological study of costal cartilage after transplantation and reasons for
      avoidance of postoperative resorption and retention of cartilage structure in
      rats.
AB  - BACKGROUND: Limited information is available on the biological status of
      transplanted cartilage from which the perichondrium has been removed. This
      article describes the histological and three-dimensional structural picture of
      cartilage, using green fluorescent protein (GFP) transgenic rats and normal wild
      rats. METHODS: Three sections of costal cartilage were harvested from 10-week-old
      wild rats. One section was used as a specimen while two were subcutaneously
      collected from the dorsal region of 10-week-old GFP rats at 4 and 8 weeks post
      transplant. The experiment was performed in two randomized groups. The
      perichondrium was removed from transplanted cartilage in the first group and
      perichondrium of transplanted cartilage remained intact in the second group.
      Histology and focused ion beam/scanning electron microscope (FIB/SEM) tomography
      were used to evaluate the transplanted cartilage. RESULTS: All 40 transplanted
      sections were harvested and no infections, exposure or qualitative change of
      cartilage matrix were seen following transplant. Histological analyses showed
      that the surface layer of the GFP-negative transplanted cartilage was replaced
      with GFP-positive chondrocytes 8 weeks post-transplant in the first group. A
      three-dimensional layer of perichondrium-like tissue reconstructed around the
      cartilage at 8 weeks was confirmed, resembling normal perichondrium. However, the
      GFP-positive chondrocytes were not replaced in the second group. CONCLUSIONS: The
      cell renewal of chondrocytes is necessary for subcutaneously transplanted
      cartilage to maintain its tissue composition over a long period of time. The
      histological and ultrastructural analyses revealed that cells from recipient
      tissue generated new chondrocytes even when cartilage was implanted after
      removing the perichondrium.

PMID- 30286674
TI  - Maternal and umbilical cord blood level of macrophage migration inhibitory factor
      and insulin like growth factor in Sudanese women with preeclampsia.
AB  - Preeclampsia is a health concern and it is the main cause of maternal and
      perinatal mortality. The macrophage migration inhibitory factor (MIF) and insulin
      like growth factor-I (IGF-I) are factors associated with preeclampsia. A case
      control (45 women in each arm) study was conducted at Saad Abualila Maternity
      Hospital (Khartoum, Sudan). The cases were of women who had preeclampsia, and the
      controls were healthy pregnant women. The clinical and obstetrical
      characteristics were gathered using a questionnaire and MIF and IGF-I levels were
      measured by ELISA. The cases and the controls (45 in each arm) were matched in
      their basic data. In comparison with the healthy controls, while the median
      (interquartile range) of the maternal MIF [8.221 (7.334-8.820) vs. 3.717 (2.385
      4.883) ng/mL, p < .001] was significantly higher, the levels of the maternal IGF
      1 [1.250 (0.670-1.980) vs. 1.939 (1.056-2.752), ng/mL, p < .001] were
      significantly lower in the women with preeclampsia. There was no significant
      difference in the cord levels of both the MIF and IGF-1 between the cases and
      controls. In linear regression, preeclampsia was the only factor that was
      significantly associated with the log of the maternal MIF (-0.338 ng/mL, p <
      .001), IGF-1 (0.293 ng/mL, p = .005) and cord MIF (-0.340 ng/mL, p < .001)
      levels. Impact statement What is already known on this subject? Macrophage
      migration inhibitory factor (MIF) has a pivotal role in pro-inflammatory
      processes during pregnancy/labour and its levels have been correlated with
      preeclampsia. Insulin like factors are produced in the liver under the
      stimulation of the growth hormones; they stimulate cell differentiation
      proliferations. IGF-I may be implicated in the pathogenesis of the adverse
      effects of preeclampsia (mainly the birth weight). What do the results of this
      study add? The current study showed a significantly higher level of MIF and lower
      level IGF-1 in the women with preeclampsia. Thus, both MIF and IGF-1 might have a
      role in the pathogeneses of preeclampsia. What are the implications of these
      findings for clinical practice and/or further research? MIF and IGF might be used
      as reliable markers to detect preeclampsia. These markers might be used as
      preventive or therapeutic elements for preeclampsia.

PMID- 30286675
TI  - Is there any relationship between benign endometrial pathologies and metabolic
      status?
AB  - The aim of this study was to assess the relation between benign endometrial
      pathologies (polyp and/or hyperplasia without atypia) and the metabolic status
      (insulin resistance and metabolic syndrome) of the patients. A total of 168 cases
      were enrolled in the study. The patients were classified according to the
      presence of benign endometrial pathologies and their menopausal status. Then, the
      subjects were evaluated according to the metabolic syndrome criteria and the
      presence of an insulin resistance. The insulin resistance levels of the cases
      were analysed by four different methods. Obesity and a waist circumference of
      greater than 88 cm were observed significantly more in the study group with
      endometrial pathologies (p = .005 and p < .001, respectively). It was also
      observed that a fasting blood glucose level of higher than 110 mg/dL increased
      the risk of developing endometrial polyps and/or hyperplasia without atypia by
      almost five folds (OR: 5.26, 95% CI: 1.25-22.12). Furthermore, an insulin
      resistance was found to be significantly high in the study group (p = .002).
      Based on the observed significant relationship between an insulin resistance and
      benign endometrial pathologies, it can be concluded that insulin resistance plays
      an important role in the development of benign endometrial pathologies. Impact
      Statement What is already known on this subject? Metabolic anomalies such as
      obesity, type 2 diabetes, hypertension and dyslipidaemia play an important role
      in abnormal endometrial proliferation. Also, these metabolic anomalies have been
      known as risk factors for type I endometrial cancer. What the results of this
      study add? A significant relationship between an insulin resistance and benign
      endometrial pathologies was observed. What the implications are of these findings
      for clinical practice and/or further research? Based on this finding, we
      concluded that an insulin resistance may play an important role in the
      development of benign endometrial pathologies. The prevention and the treatment
      of obesity as a key factor of developing an insulin resistance, may reduce not
      only the incidence of malignant endometrial pathologies, but also the incidence
      of benign pathologies and of a malignant transformation.

PMID- 30286676
TI  - Pharmacokinetic study of the prokinetic ABCs liquiritigenin, naringenin and
      hesperitin following the oral administration of Si-Ni-San decoction to functional
      dyspepsia patients.
AB  - 1. The pharmacokinetics (PKs) analysis of compounds absorbed after the oral
      administration of Si-Ni-San (SNS) decoction to functional dyspepsia (FD) patients
      was designed to detect whether the effects were similar to prokinetics
      administered to healthy rats, without ethical limitation. 2. First, the absorbed
      compounds, liquiritigenin (L), naringenin (N) and hesperitin (H) in the plasma
      were identified by UPLC-MS/MS following the oral administration of SNS decoction
      to subjects with FD. Next, the natural ratio of LNH in the SNS decoction was
      determined by UPLC. Third, gastric emptying and intestinal transit after the oral
      administration of LNH, in combination or alone, was compared with those observed
      after SNS administration in healthy rats. Additionally, the clinical PKs of LNH
      was studied. 3. The prokinetic efficacy of LNH administered at their natural
      ratios (7.5:5:1) increased dose-dependently and was better than the observed
      efficacy when administered alone in rats. Analysis of the clinical PK parameters,
      calculated using a one-compartment model, showed that the Cmax parameters of LNH
      in 3, 4 and 4 h were 639.17, 410.00 and 181.67 MUg/L, respectively. 4. The
      clinical herbal PK analysis of the absorbed LNH preclinical prokinetic compounds,
      in their natural ratio from SNS, highlights the impact of an herbal translational
      pharmacology study.

PMID- 30286677
TI  - Early Onset Allergic Proctitis in a Preterm Neonate-A Case Report and Review of
      the Literature.
AB  - Cow's milk protein allergy/intolerance (CMPA/CMPI) is a common entity in the
      pediatric population with a nonspecific presentation ranging from
      gastrointestinal symptoms to systemic manifestations. Most infants with CMPI are
      term, and symptoms often appear in the week following the introduction of cow's
      milk-based formula. There is typically a significant delay in the onset of milk
      allergy in premature infants compared to full term. We report a rare case of a
      premature neonate who presented with symptoms of CMPA within the first 2 days of
      life.

PMID- 30286678
TI  - Accuracy of internet images of ligamentous knee injuries.
AB  - BACKGROUND: The internet is an easily accessible resource for both providers and
      patients. Despite this, the internet is not peer reviewed, leaving searches
      subject to inaccuracies, especially with regards to medical information. The
      purpose of this study was to review internet images of anterior cruciate ligament
      (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL), and
      lateral collateral ligament (LCL) tears using two popular search engines: Google
      and Bing. METHODS: A search query was performed on both Google and Bing for the
      following terms: 'ACL tear', 'PCL tear', 'MCL tear' and 'LCL tear'. The first 100
      images of each individual search were analyzed by three independent orthopedists.
      RESULTS: The inter-rater reliability was very good for PCL tear on Bing
      (Cronbach's alpha = 0.89) and excellent (Cronbach's alpha > 0.9) for the
      remainder of the search queries. When comparing Google to Bing, the only
      significant difference occurred in the ACL group, with Bing returning a
      significantly greater number of correct images 60%, 95% CI: 53.2 - 66.7%)
      compared to Google (45% correct, 95% CI: 38.1-51.8%), p = 0.034. With regards to
      the other ligaments Bing was more accurate than Google for PCL (39% versus 38%),
      and LCL (32% to 30%). Both sites were 48% accurate for MCL tear. CONCLUSION:
      Ultimately, our study revealed that physicians should take an active role in
      making high quality, easy to understand medical resources and anatomic diagrams
      available to their patients to avoid confusion and enhance understanding when
      querying the internet for additional information regarding their condition.

PMID- 30286679
TI  - Adherence to medication in children and adolescents with asthma: methods for
      monitoring and intervention.
AB  - INTRODUCTION: Poor adherence in children with asthma is a major cause of asthma
      attacks and poor control, leads to large health-care costs, and has been
      identified as a factor in asthma deaths. However, it is difficult to detect and
      frequently overlooked leading to inappropriate escalation of asthma treatment.
      There is a need for cost effective ways to monitor adherence in order to
      intervene to change this modifiable behavior. Areas covered: Several measurement
      tools have been developed to assess adherence in adults and children with asthma.
      The current methods for measuring adherence, both subjective and objective, have
      several flaws and even the current gold standard, electronic monitoring devices
      (EMDs), has limitations. This review will outline and critique the adherence
      monitoring tools and highlight ways in which they have been used for the purpose
      of intervention. Expert commentary: Although advances have been made in adherence
      monitoring, we still have some way to go in creating the ideal monitoring tool.
      There are no validated tailored self-monitoring questionnaires for children with
      asthma and most objective measures, such as prescription refill rate and weighing
      canisters, overestimate adherence. Current EMDs, although useful, need improved
      accuracy to ensure that both actuation and inhalation are measured, and the
      devices need to be affordable for use in routine health-care practice.

PMID- 30286680
TI  - The importance of inhibitor eradication in clinically complicated hemophilia A
      patients.
AB  - INTRODUCTION: Inhibitors against factor VIII (FVIII), which develop in around 20
      30% of patients with severe hemophilia A, represent a significant complication of
      on-demand or prophylactic FVIII therapy. Currently, the main treatment option for
      inhibitor patients is eradication using immune tolerance induction (ITI) therapy.
      Areas covered: This article reviews inhibitor eradication in clinically
      complicated hemophilia A patients. The benefits and disadvantages of ITI therapy
      are discussed, with reference to the new nonfactor replacement agents such as
      emicizumab, which are becoming available. Expert commentary: At present, ITI
      therapy is the method of choice for all inhibitor patients, but as alternative
      treatment options become increasingly available, this may change in the future.
      Despite the development of nonfactor replacement agents, ITI therapy is likely to
      maintain a key role in the management of inhibitor patients, although changes in
      ITI therapy regimens including the timing of ITI initiation, the dosing regimen,
      the management of thrombotic risk or safety, laboratory assessment of ITI
      outcomes, and maintenance treatment after ITI success, may be necessary.

PMID- 30286681
TI  - The influence of language and culture on cognitive assessment tools in the
      diagnosis of early cognitive impairment and dementia.
AB  - INTRODUCTION: Cognitive assessment tools measure cognitive impairment and
      complement biomarkers to link cognitive symptoms with pathophysiological
      processes underlying dementia. However, language and cultural differences in
      multilingual populations can influence the interpretation of cognitive assessment
      tools when applied in cross-cultural and multinational studies. Areas covered:
      This article examines the influence of culture and language on the interpretation
      of the Mini-Mental State Examination, Montreal Cognitive Assessment, and
      Alzheimer's Disease Assessment Scale-cognitive subscale, which are more commonly
      used worldwide. It discusses how this impacted multinational studies. Lastly, it
      presents language-neutral tools such as the Visual Cognitive Assessment Test,
      which do not require translation when applied in multilingual populations. Expert
      commentary: Linguistic and cultural variation within tools due to translation and
      differences in administration introduce method bias and differential item
      functioning, which influence the interpretation of cognitive scores in
      multinational studies. The ultimate goal is to have a tool that accurately
      measures cognitive impairment, yet with minimal influence from linguistic,
      cultural, educational, and demographic differences, through concerted
      international efforts to harmonize the development and validation of tools. While
      recently developed visual-based language-neutral tools show promise in the early
      detection of cognitive impairment, further validation will be required for these
      tools to be applied internationally.

PMID- 30286682
TI  - Advances in contraceptive vaginal rings: what does the future hold?
AB  - INTRODUCTION: Contraceptive vaginal rings (CVRs) are good contraceptive options
      because they do not require skilled providers, are self-administered, and show a
      higher stability of drug diffusion. Area covered: This article provides a review
      of the developments made with CVRs over the past number of years, while giving
      focus to the latest CVRs that have gone through clinical development. The author
      of the article also provides an expert perspective on the future of these useful
      therapeutic options. Expert opinion: Pharmacokinetic studies have shown that
      segesterone, an absorbable progestin that is used alone or in combination with
      ethinyl estradiol (EE) or E2, is the CVR of choice at this present time. Indeed,
      segesterone has demonstrated safety and efficacy as a CVR and is also an
      appropriate option for lactating women, as they are not absorbed orally. However,
      good cycle control is important for improved CVR adherence. CVRs that allow the
      combination of more than one drug may unravel another multi-purpose use when
      combined with microbicides and could provide combined protection to women who
      wish to protect themselves from pregnancy and sexually transmitted infection.

PMID- 30286683
TI  - Automated monitoring of mouse feeding and body weight for continuous health
      assessment.
AB  - Routine health assessment of laboratory rodents can be improved using automated
      home cage monitoring. Continuous, non-stressful, objective assessment of rodents
      unaware that they are being watched, including during their active dark period,
      reveals behavioural and physiological changes otherwise invisible to human
      caretakers. We developed an automated feeder that tracks feed intake, body
      weight, and physical appearance of individual radio frequency identification
      tagged mice in social home cages. Here, we experimentally induce illness via
      lipopolysaccharide challenge and show that this automated tracking apparatus
      reveals sickness behaviour (reduced food intake) as early as 2-4 hours after
      lipopolysaccharide injection, whereas human observers conducting routine health
      checks fail to detect a significant difference between sick mice and saline
      injected controls. Continuous automated monitoring additionally reveals
      pronounced circadian rhythms in both feed intake and body weight. Automated home
      cage monitoring is a non-invasive, reliable mode of health surveillance allowing
      caretakers to more efficiently detect and respond to early signs of illness in
      laboratory rodent populations.

PMID- 30286684
TI  - Youth Speak Out on School Food Environments.
AB  - In Philadelphia, over 40% of youth are overweight or obese. The objective in this
      assessment was to learn about urban residents' perspectives regarding the local
      food environment and its impact on eating behaviors. Using photo-elicitation, 20
      adolescents reflected on their food environments through photographs and
      corresponding interviews. Without specific prompting from interviewers, every
      participant raised concerns about their school food environments, which they
      commonly found to be unhealthy and unappealing. Participants' responses reflected
      four themes: (1) mixed reviews regarding the healthfulness of school vending
      machines, (2) lunch from home versus lunch from school, (3) factors that
      influenced food choice at school, and (4) critiques of school food environments.
      Students embraced the photo-elicitation approach as a way to convey their
      concerns and to suggest opportunities for improvements. School nurses, who are
      trusted by students and school personnel, are well-positioned to solicit student
      input and advocate for healthier school food environments.

PMID- 30286685
TI  - Voices We Forget-Danish Students Experience of Returning to School Following
      Parental Bereavement.
AB  - This study explores how Danish students experience returning to school following
      parental bereavement. Eighteen focus group interviews with 39 participants aged 9
      to 17 years were conducted. All participants had experienced the loss of a
      primary caregiver. Data collection was divided into two phases. In Phase I, 22
      participants from four grief groups were interviewed 4 times over the course of a
      year. During Phase II, confirmatory focus groups were undertaken with the 17
      participants. This article explores findings related to the four themes of
      initial school response, long-term support, challenges within the class, and
      academic challenges. The study found that (a) students struggle to reconnect with
      classmates following the return to school and often feel alone, (b) schools fail
      to have guidelines in place for what they are allowed to do if becoming sad the
      class, and (c) schools seem to forget their loss as time passes.

PMID- 30286686
TI  - A Model of Transcorporeal Communication: Communication Toward/With/to the
      Deceased.
AB  - Research indicates that people maintain a connection with deceased loved ones,
      which can be healthy for the bereaved individuals. To maintain these bonds,
      people readily admit to communicating with the deceased. Although communication
      with the deceased shares similarities with traditional models of interpersonal
      communication, it is distinctly different. Interviews with 20 individuals
      revealed support for a model of transcorporeal communication, communication to
      people who do not maintain a physical presence. This communication includes the
      components of sender, inner representation of the deceased as receiver, message,
      feedback based on what the sender believes the deceased would say, and a
      metaphysical element. Implications of transcorporeal communication for griefwork
      are also discussed.

PMID- 30286687
TI  - Event Centrality and Bereavement Symptomatology: The Moderating Role of Meaning
      Made.
AB  - The centrality of a loss to a bereaved individual's identity is associated with
      greater symptomatology, whereas meaning made of a loss is associated with
      positive outcomes. This article examines meaning made as a moderator of the
      relationship between event centrality and symptomatology. Our sample consisted of
      204 bereaved undergraduate university students. Centrality was assessed using the
      Centrality of Events Scale, meaning made was assessed using the Integration of
      Stressful Life Experiences Scale, and symptomatology was assessed using the
      posttraumatic stress disorder Checklist-Civilian and Inventory of Complicated
      Grief-Revised. Meaning made had a significant moderating effect on the
      relationship between centrality and both measures of symptomatology. At lower
      levels of meaning made, centrality had a strong and positive association with
      symptomatology; at higher levels of meaning made, this association became weaker.
      These results suggest that meaning made is the key to understanding how
      centrality affects bereavement outcomes.

PMID- 30286688
TI  - Rapid Central Vein Assessment (RaCeVA): A systematic, standardized approach for
      ultrasound assessment before central venous catheterization.
AB  - Ultrasound technology has revolutionized the practice of safer vascular access,
      for both venous and arterial cannulation. The ability to visualize underlying
      structures of the chest, neck, and upper/lower extremities provides for greater
      success, speed, and safety with all vascular access procedures. Ultrasound not
      only yields superior procedural advantages but also provides a platform to
      perform a thorough assessment of the vascular structures to evaluate vessel
      health, viability, size, and patency, including the location of other important
      and best avoided anatomical structures-prior to performing any procedures. Such
      assessment is best performed using a systematic and standardized approach, as the
      Rapid Central Vein Assessment, described in this study.

PMID- 30286689
TI  - Psychometric Characteristics of Duke Social Support Index Among Elderly Suicide
      in Rural China.
AB  - We recruited 242 elderly suicides and 242 controls above 60 years to conduct face
      to-face interviews by psychological autopsy to examine the psychometric
      characteristics of the Duke Social Support Index (DSSI) in rural China. DSSI had
      high internal consistency, with Cronbach's alphas of .89 and .90 in suicides and
      controls, respectively. DSSI was significantly and negatively correlated to
      loneliness in both samples. Confirmatory factor analysis basically supported the
      original structure of DSSI, but Item 4 had low factor loading in controls. In
      conclusion, DSSI has satisfactory reliability and acceptable validity in
      evaluating social support in the elderly suicide study in China.

PMID- 30286690
TI  - Ethnoregional Dynamics of Intimate Partner Violence Against Women in Nigeria.
AB  - Intimate partner violence (IPV) is a reality the average Nigerian woman has to
      grapple with everyday. Ethnicity and place of residence play a pivotal role in
      the social realities of Nigerian women, especially with their experience of IPV.
      However, there is a paucity of reviews examining the impact of ethnicity and
      place of residence on women's experiences of IPV in Nigeria. This study seeks to
      explore the ethnoregional dynamics of IPV from the range of studies undertaken on
      the subject matter. Eighteen studies meant the inclusion criteria for analysis.
      The major criteria for selecting studies for analysis were peer-reviewed studies
      on IPV against women and studies on a Nigerian population, regardless of the
      nationality of the authors. Databases like the University of Saskatchewan
      Library, ProQuest, Sociological Abstracts, and Journal Storage ( JSTOR) were used
      in searching for peer-reviewed studies. The study revealed that Igbo women tend
      to experience IPV more than Yoruba and Hausa women. The study also found that
      rural women tend to experience IPV more than urban women. The study points out
      some of the services available for female victims of IPV and the possible
      strategies that can be adapted to reach them effectively.

PMID- 30286691
TI  - Anti-inflammatory effects of Kaempferol on Helicobacter pylori-induced
      inflammation.
AB  - : Inflammation induced by Helicobacter pylori infection related to gastric
      carcinogenesis. In this study, we have investigated the anti-inflammatory effect
      and its mechanism of kaempferol in the inflammatory response caused by H. pylori
      infection in vitro. We found that kaempferol reduced the expression of pro
      inflammatory cytokines (TNF-alpha, IL-1beta, and IL-8) and production of IL-8 in
      AGS cells. In addition, kaempferol suppressed translocation of cytotoxin
      associated gene A (CagA) and vacuolating cytotoxin A (VacA) of H. pylori to AGS
      cells. It was due to decreased transcription of type IV secretion system (T4SS)
      components involved in CagA injection and secretion system subunit protein A
      (SecA) of type V secretion system (T5SS) involved in VacA secretion by
      kaempferol. In conclusion, kaempferol shows the anti-inflammatory effect by
      suppressing the translocation of CagA and VacA proteins and leading to the down
      regulation of pro-inflammatory cytokines. ABBREVIATIONS: CagA: cytotoxin
      associated gene A; VacA: vacuolating cytotoxin A; T4SS: type IV secretion
      systems; SecA: secretion system subunit protein A; T5SS: type V secretion system.

PMID- 30286692
TI  - The hyoid bone: an overview.
AB  - The hyoid bone is a small horseshoe-shaped bone located between the mandible and
      the shoulder girdle. It is classified as a sesamoid bone which means it is a
      freely floating bone. However, it is anything but freely floating. The hyoid bone
      is a vestigial structure and is found as part of the tongue in lower animal
      forms. The hyoid bone is attached to the base of the skull, the mandible, the
      tongue, the larynx, and the scapular belt. Even though the hyoid bone is an
      important structure, it has not received the attention that it deserves. It
      participates in the function of speech, respiration, mastication, and swallowing,
      as well as maintaining the patency of the airway between the oropharynx and the
      tracheal rings. Knowledge of the anatomy and physiology of the hyoid is necessary
      for recognition of the clinical presentation of related disorders and syndromes.

PMID- 30286693
TI  - Ganglion Cytology: A Novel Rapid Method for the Diagnosis of Equine Dysautonomia.
AB  - Equine dysautonomia (grass sickness) is characterized by autonomic neuronal
      degeneration and is often fatal. As outbreaks occur, rapid diagnosis is essential
      but confirmation currently requires histological examination. This study
      evaluated diagnostic accuracy of cytological examination of cranial cervical
      ganglion (CCG) scrapings for dysautonomia diagnosis. CCG smears from 20 controls
      and 16 dysautonomia cases were stained with May-Grunwald Giemsa (MGG),
      hematoxylin and eosin (HE), and cresyl fast violet (CFV), with HE-stained
      histological sections of CCG as gold standard for diagnosis. Examining all 3
      stains together, the sensitivity and specificity were 100%. Occasional individual
      smears (4/107, 3.7%) were nondiagnostic due to low cellularity, and in a few
      individual smears the final diagnosis was correct but more tentative (CFV: 5/33
      [15.1%], HE: 2/34 [5.9%], and MGG: 4/36 [11.1%]), due to low cellularity or
      suboptimal cell morphology. CCG cytology was considered reliable for rapid
      postmortem diagnosis of equine dysautonomia, particularly using MGG.

PMID- 30286694
TI  - A meta-analytic perspective on the valid use of subjective human judgement to
      make medical school admission decisions.
AB  - While medical educators appear to believe that admission to the medical school
      should be governed, at least in part, by human judgement, there has been no
      systematic presentation of evidence suggesting it improves selection. From a fair
      testing perspective, legal, ethical, and psychometric considerations, all dictate
      that the scientific evidence regarding human judgement in selection should be
      given consideration. To investigate the validity of using human judgements in
      admissions, multi-disciplinary meta-analytic research evidence from the wider
      literature is combined with studies from within medical education to provide
      evidence regarding the fairness and validity of using interviews and holistic
      review in medical school admissions. Fourteen studies, 6 of which are meta
      analytic studies that summarized 292 individual studies, were included in the
      final review. Within these studies, a total of 33 studies evaluated the
      reliability of the traditional interview. These studies reveal that the interview
      has low to moderate reliability (~.42) which significantly limits its validity.
      This is confirmed by over 100 studies examining interview validity which
      collectively show interview scores to be moderately correlated with important
      outcome variables (corrected value ~.29). Meta-analyses of over 150 studies
      demonstrate that mechanical/formula-based selection decisions produce better
      results than decisions made with holistic/clinical methods (human judgement).
      Three conclusions regarding the use of interviews and holistic review are
      provided by these meta-analyses. First, it is clear that the traditional
      interview has low reliability and that this significantly limits its validity.
      Second, the reliable variance from interview scores appears moderately predictive
      of outcomes that are relevant to consider in medical school admission. And third,
      the use of holistic review as a method of incorporating human judgement is not a
      valid alternative to mechanical/statistical approaches as the evidence clearly
      indicates that mechanistic methods are more predictive, reliable, cost efficient,
      and transparent.

PMID- 30286695
TI  - Identification and expression analysis of MinD gene involved in plastid division
      in cassava.
AB  - Cassava is a tropical crop known for its starchy root and excellent properties.
      Considering that starch biosynthesis in the amyloplast is affected by its
      division, it appears conceivable that the regulation of plastid division plays an
      important role in starch accumulation. As a member of the Min system genes, MinD
      participated in the spatial regulation of the position of the plastid division
      site.In our studies, sequence analysis and phylogenetic analysis showed that
      MeMinD has been highly conserved during the evolutionary process. Subcellular
      localisation indicated that MeMinD carries a chloroplast transit peptide and was
      localised in the chloroplast. Overexpression of MeMinD resulted in division site
      misplacement and filamentous formation in E. coli, indicating that MeMinD protein
      was functional across species. MeMinD exhibited different spatial and temporal
      expression patterns which was highly expressed in the source compared to that in
      the sink organ.

PMID- 30286696
TI  - Japanese Rice Wine can reduce psychophysical stress-induced depression-like
      behaviors and Fos expression in the trigeminal subnucleus caudalis evoked by
      masseter muscle injury in the rats.
AB  - We determined if Japanese Rice Wine (Sake) had inhibitory effects on stress
      induced enhancement of masseter muscle (MM) nociception in the rats. Male rats
      were subjected to the repeated forced swim stress (FS) or sham conditionings from
      Day -3 to -1. Daily administration of Sake or saline was conducted after each
      stress conditioning. At Day 0 the number of Fos positive cells, a marker for
      neural activity, was quantified at the trigeminal subnucleus caudalis (Vc) region
      by MM injury with formalin. FS increased MM-evoked Fos expression in the Vc
      region, which was inhibited by Sake compared to saline administration. Sake did
      not alter the number of Fos positive cells under sham conditions, indicating that
      inhibitory roles of Sake on neural activity in the Vc region were seen under FS
      conditions. These findings indicated that Sake had inhibitory roles on stress
      induced MM nociception at the Vc region in our experimental conditions.

PMID- 30286697
TI  - Case Series of 23 Patients Who Developed Fatal Radiation Pneumonitis After
      Stereotactic Body Radiotherapy for Lung Cancer.
AB  - The purpose of this study was to examine the characteristics and treatment plans
      of patients who experienced fatal radiation pneumonitis after stereotactic body
      radiation therapy for primary or oligometastatic lung cancer. Records of 1789
      patients treated with stereotactic body radiation therapy for primary or
      oligometastatic lung cancer were retrospectively reviewed to identify those who
      developed fatal radiation pneumonitis. Twenty-three (1.3%; 18 men and 5 women)
      patients developed fatal radiation pneumonitis after stereotactic body radiation
      therapy for lung cancer; their median age was 74 years. The mean Krebs von den
      Lungen-6 level and percent vital capacity were 1320 U/mL and 82%, respectively.
      Prestereotactic body radiation therapy computed tomography revealed pulmonary
      interstitial change in 14 (73.7%) of 19 patients in whom computed tomography data
      could be reviewed. Seven (30.4%) of 23 patients had regularly used steroids. The
      median time duration between stereotactic body radiation therapy commencement and
      pneumonia symptom appearance was 75 (range: 14-204) days. Median survival time
      following pneumonia symptom appearance was 53 (range: 4-802) days. The 6- and 12
      month overall survival rates were 34.8% and 13.0%, respectively. The 6-month
      overall survival rates in patients with and without heart disease were 50.0%,
      16.7%, and 46.7% for heart disease existence, respectively. There were 4 patients
      in whom fatal radiation pneumonitis occurred within 2 months after stereotactic
      body radiation therapy and who died within 1 month. Three of them had no
      pulmonary interstitial change before stereotactic body radiation therapy, but had
      heart disease. In summary, the survival time in this case series was generally
      short but varied widely. More than half of the patients had pulmonary
      interstitial change before stereotactic body radiation therapy, although
      immediately progressive fatal radiation pneumonitis was also observed in patients
      without pulmonary interstitial change. True risk factors for fatal radiation
      pneumonitis should be examined in a prospective study with a larger cohort.

PMID- 30286699
TI  - Bizarre extensive erythematous plaques on the abdomen.
AB  - We present a rare case report of a 28-year-old man with a five-month history of
      bizarre extensive erythematous plaques on the abdomen extending in a dermatomal
      fashion to the left upper back.

PMID- 30286698
TI  - In their own words: stressors facing medical students in the millennial
      generation.
AB  - BACKGROUND: Medical student exposure to stressors is associated with depression,
      burnout, somatic distress, decreases in empathy, serious thoughts about dropping
      out of medical school, suicidal ideation, and poor academic performance. Despite
      this, there have been no recent, multicenter, qualitative studies assessing
      medical students' perceptions of their greatest stressor(s). OBJECTIVE: The goal
      of this study was to identify the most significant stressors noted by medical
      students themselves, in order to inform the development of programs and policies
      to reduce medical student distress. DESIGN: Medical students from the nine
      schools in the state of Florida were invited to complete an anonymous online
      questionnaire assessing wellness and distress. Students were notified that all
      responses were voluntary and that individual responses would not be linked to
      themselves or their program. This paper focuses on students' responses to fixed
      response items regarding their experience of stress and open-ended responses to
      the following question: 'What do you consider to be the greatest stressor(s)
      facing medical students?' Qualitative data were analyzed using the Grounded
      Theory method of data analysis. RESULTS: Results confirmed the impact of several
      stressors highlighted in previous studies (e.g., excessive workload, difficulties
      with studying and time management, conflicts in work-life balance and
      relationships, medical school peer relations, health concerns, and financial
      stressors). However, students also reported unique system-level concerns that
      have not consistently been highlighted in past research (e.g., medical school
      administrative failures, concerns about lack of assistance with career planning,
      and assessment-related performance pressure. CONCLUSIONS: Though individually
      focused interventions have demonstrated some success, medical students self
      report stressors that may be better addressed through system-level changes.

PMID- 30286700
TI  - Granuloma multiforme: an uncommon differential for leprosy.
AB  - Granuloma multiforme (GM) is a chronic granulomatous skin condition which is
      clinically characterised by annular lesions mainly over sun-exposed areas and
      histologically by focal necrobiosis and histiocytic granulomas. Its significance
      lies in the fact that it can clinically resemble tuberculoid leprosy and hence it
      can be missed. Here, we report a case of GM from India in a 55-year-old female
      agriculturist, with multiple asymptomatic large annular rings of papules over the
      photo-distributed areas. Histopathology helps in confirming the diagnosis and in
      differentiating it from similar clinical and histologic mimics such as granuloma
      annulare, tuberculoid leprosy, interstitial granulomatous dermatitis or annular
      sarcoid. Though a high degree of suspicion is needed to diagnose GM, it should be
      considered as a differential for various annular conditions.

PMID- 30286701
TI  - Rational discovery of a SOD1 tryptophan oxidation inhibitor with therapeutic
      potential for amyotrophic lateral sclerosis.
AB  - Formation of Cu, Zn superoxide dismutase 1 (SOD1) protein inclusions within motor
      neurons is one of the principal characteristics of SOD1-related amyotrophic
      lateral sclerosis (ALS). A hypothesis as to the nature of SOD1 aggregation
      implicates oxidative damage to a solvent-exposed tryptophan as causative. Here,
      we chart discovery of a phenanthridinone based compound (Lig9) from the NCI
      Diversity Set III by rational methods by in silico screening and crystallographic
      validation. The crystal structure of the complex with SOD1, refined to 2.5 A,
      revealed that Lig9 binds the SOD1 beta-barrel in the beta-strand 2 and 3 region
      which is known to scaffold SOD1 fibrillation. The phenanthridinone moiety makes a
      substantial pi - pi interaction with Trp32 of SOD1. The compound possesses a
      significant binding affinity for SOD1 and inhibits oxidation of Trp32; a critical
      residue for SOD1 aggregation. Thus, Lig9 is a good candidate from which to
      develop a new library of SOD1 aggregation inhibitors through protection of Trp32
      oxidation.

PMID- 30286702
TI  - Construction of a potato fraction library for the investigation of functional
      secondary metabolites.
AB  - A potato fraction library was constructed to investigate functional secondary
      metabolites from 8 cultivars: Kitahime, Pilka, Sakurafubuki, Atlantic, Toyoshiro,
      Snowden, Kitamurasaki, and Northern Ruby, which were divided into flower, leaf,
      stem, roots, tuber peel, and tuber. Each fraction was a semi-purified extract and
      about 800 fractions were prepared for the library. They were analyzed by DAD
      LC/MS to obtain structural information and were evaluated for various biological
      activities. LC/MS data showed that each part had a specific characteristic for
      their constituents supported by principal component analysis (PCA). Approximately
      40% of fractions showed significant biological activities at 30 MUg/mL,
      especially the flower fractions showed strong cytotoxicity. PCAs based on the
      activity and LC/MS data suggested that the strong cytotoxicity of flowers was
      derived from a complex mixture of potato glycoalkaloids. In addition, tuber peel
      fractions showed strong antimalarial activity, which had not been reported
      before. Also, some fractions showed significant antibacterial activities.

PMID- 30286703
TI  - Ergothioneine production with Aspergillus oryzae.
AB  - : To establish a reliable and practical ergothioneine (ERG) supply, we employed
      fermentative ERG production using Aspergillus oryzae, a fungus used for food
      production. We heterologously overexpressed the egt-1 and -2 genes of Neurospora
      crassa in A. oryzae and succeeded in producing ERG (231.0 mg/kg of media, which
      was 20 times higher than the wild type). ABBREVIATIONS: ERG: ergothioneine; HER:
      hercynine; Cys-HER: hercynylcysteine-sulfoxide; SAM: S-adenosylmethionine; SAH: S
      adenosylhomocysteine; l-His: l-histidine; l-Cys: l-cysteine; LC-ESI-MS: liquid
      chromatography-electrospray ionization-mass spectrometry.

PMID- 30286704
TI  - The effects of a calf pump device on second half performance of a simulated
      soccer match in competitive youth players.
AB  - During soccer matches, performance decrements have been reported that relate to
      both physical abilities and technical skills. To investigate the effects of low
      frequency electrical stimulation LFES (VeinoplusSport(r), Ad Rem Technology,
      France) administered during half-time recovery on performance alterations during
      the second half. Twenty-two highly trained young players undertook a soccer-match
      simulation (SAFT90). During half-time, they were randomly assigned to LFES group
      or Placebo group. Each half was split into 3 bouts of 12 minutes. Following each
      bout, maximal strike speed (MSS), sprint test (ST), maximal sprint accelerations
      (MA) and metabolic power (MP) were determined in both groups. Arterial (AF) and
      venous flows (VF) were measured at rest and at the end of half-time. LEFS group
      exhibited beneficial effects on performance compared to the Placebo group with a
      likely effect for MSS, ST, MA, and a possible effect for MP. AF and VF increased
      statistically more in LEFS group compared to Placebo group. The use of specific
      calf-pump LFES during half-time of a youth simulated soccer match attenuated the
      decrease in performance during the second half compared to Placebo group. This
      effect is most marked at the beginning of the second half with regards to
      explosive parameters.

PMID- 30286705
TI  - Canine Cerebral Intravascular Lymphoma: Neuropathological and Immunohistochemical
      Findings.
AB  - Intravascular lymphoma (IVL) is a rare angiotropic large-cell lymphoma in which
      neoplastic lymphocytes proliferate within the lumina of small blood vessels in
      the absence of a primary extravascular mass or leukemia. This study included 10
      cases of canine IVL restricted to the CNS. Dogs had an average age of 8 years and
      neurological signs mainly referred to brain involvement such as depression,
      seizures, and ambulatory deficits. Gross examination at necropsy showed focal
      extensive or multiple hemorrhagic areas mainly distributed in the telencephalon
      and diencephalon. Histopathologically, numerous veins and capillaries were filled
      with neoplastic lymphoid cells, accompanied by edema, hemorrhage, and thrombosis.
      Immunohistochemistry (IHC) for CD3, CD20, and PAX5 was performed to phenotype the
      neoplastic lymphocytes. IHC for CD44 and CD29 were used to investigate the
      pathogenetic mechanism leading to the intravascular aggregation of the neoplastic
      lymphocytes. The same IHC panel was applied to 8 cases of primary and metastatic
      canine CNS lymphoma in order to compare IVL immunoreactivity. Three IVLs were
      typified as T-cell, 3 as B-cell, and 4 as non-T non-B. Neoplastic lymphocytes
      showed marked expression of CD44 in all IVL cases, and CD29-immunolabeled cells
      were observed in 4 IVLs. CD44 immunoreactivity was consistent with the findings
      reported in human IVL, suggesting a predisposition to the formation of lymphocyte
      aggregates. CD29 was inconsistently immunonegative in canine IVL, confirming only
      partially the pathogenetic mechanism suggested for the human counterpart.

PMID- 30286706
TI  - Identification of an aldehyde oxidase involved in indole-3-acetic acid synthesis
      in Bombyx mori silk gland.
AB  - : Auxin is thought to be an important factor in the induction of galls by galling
      insects. We have previously shown that both galling and nongalling insects
      synthesize indole-3-acetic acid (IAA) from tryptophan (Trp) via two
      intermediates, indole-3-acetaldoxime (IAOx) and indole-3-acetaldehyde (IAAld). In
      this study, we isolated an enzyme that catalyzes the last step "IAAld -> IAA"
      from a silk-gland extract of Bombyx mori. The enzyme, designated "BmIAO1",
      contains two 2Fe-2S iron-sulfur-cluster-binding domains, an FAD-binding domain,
      and a molybdopterin-binding domain, which are conserved in aldehyde oxidases.
      BmIAO1 causes the nonenzymatic conversion of Trp to IAAld and the enzymatic
      conversion of IAOx to IAA, suggesting that BmIAO1 alone is responsible for IAA
      production in B. mori. However, a detailed comparison of pure BmIAO1 and the
      crude silk-gland extract suggested the presence of other enzymes involved in IAA
      production from Trp. ABBREVIATIONS: BA: benzoic acid; CE: collision energy; CXP:
      collision cell exit potential; DP: declustering potential; IAA: indole-3-acetic
      acid; IBI1: IAA biosynthetic inhibitor-1; IAAld: indole-3-acetaldehyde; ICA:
      indole-3-carboxylic acid; IAOx: indole-3-acetaldoxime; IEtOH: indole-3-ethanol;
      LC-MS/MS: liquid chromatography-tandem mass spectrometry; Trp: tryptophan.

PMID- 30286707
TI  - Investigating the Degree of Reliable Change Among Persons Assigned to Receive
      Mental Health Peer Specialist Services.
AB  - OBJECTIVE:: Peer specialists are individuals with mental illness and substance
      use disorders trained to use their experiences to help others with similar
      disorders. Evidence for the effectiveness of peer specialist services has been
      mixed in previous randomized trials using intent-to-treat analyses, possibly
      because of variation in the intensity of treatment delivered. This study, which
      was part of a larger randomized trial, assessed whether level of peer specialist
      engagement was associated with reliable positive change on measures of
      psychiatric symptoms and hope. METHODS:: The Reliable Change Index was used to
      compute whether veterans (N=140) achieved reliable positive change on
      standardized baseline-to-posttest assessments of psychiatric symptoms and hope.
      Logistic regression analyses were conducted to predict positive change in
      symptoms and hope by level of peer specialist engagement, with controls for
      relevant demographic factors, several baseline mental health and substance abuse
      measures, and service use during the study. RESULTS:: Logistic regression models
      showed that veterans with higher peer specialist engagement were more likely than
      those in a control group to show reliable positive change in psychiatric symptoms
      but not in hope. Compared with the control group, those with lower peer
      specialist engagement did not show positive change on either measure. White
      veterans were less likely than those from minority groups to exhibit positive
      change in psychiatric symptoms. CONCLUSIONS:: Results suggest that peer
      specialists can benefit those with mental illnesses and substance use disorders
      who engage in more frequent interactions. Studies are needed to further assess
      the circumstances under which peer specialists can be effective.

PMID- 30286708
TI  - Racial and Ethnic Differences in Use of State-Operated Inpatient Substance Abuse
      Services, 2004-2005 Versus 2010-2011.
AB  - OBJECTIVE:: This study examined ethnic-racial differences in referral source,
      length of stay, legal status, and diagnosis in state-operated substance abuse
      inpatient treatment in Connecticut. METHODS:: Data from 2004-2005 (N=1,484) and
      from 2010-2011 (N=4,529) were investigated with regression analyses. RESULTS:: At
      both time points, African Americans were more likely than other groups to be
      referred by criminal justice sources, Hispanics were more likely than whites to
      be referred by other sources, and whites were more likely than African Americans
      to have emergency-crisis admissions; length of stay was shorter for Hispanics
      than for whites and longer for African Americans than for whites and Hispanics;
      and Hispanics were less likely than other groups to have an alcohol use disorder,
      more likely than other groups to have a drug use disorder, and more likely than
      whites to receive a discharge diagnosis of a personality disorder from cluster B.
      CONCLUSIONS:: Targeted interventions to address racial-ethnic differences in
      inpatient addiction treatment are needed.

PMID- 30286709
TI  - Use of a Web-Based Shared Decision-Making Program: Impact on Ongoing Treatment
      Engagement and Antipsychotic Adherence.
AB  - OBJECTIVE:: The authors examined the impact of a Web-based shared decision-making
      application, MyCHOIS-CommonGround, on ongoing outpatient mental health treatment
      engagement (all users) and antipsychotic medication adherence (users with
      schizophrenia). METHODS:: An intervention study was conducted by comparing
      Medicaid-enrolled MyCHOIS-CommonGround users in 12 participating mental health
      clinics (N=472) with propensity score-matched adults receiving services in
      nonparticipating clinics (N=944). Medicaid claims were used to assess ongoing
      treatment engagement and antipsychotic adherence (among individuals with
      schizophrenia) one year prior to and after entry into the cohort. Multilevel
      linear models were conducted to estimate the effects of the MyCHOIS-CommonGround
      program over time. RESULTS:: No differences during the baseline year were found
      between the MyCHOIS-CommonGround group and the matched control group on
      demographic, diagnostic, or service use characteristics. At one-year follow-up,
      engagement in outpatient mental health services was significantly higher for
      MyCHOIS-CommonGround users than for the control group (months with a service,
      8.54+/-.22 versus 6.95+/-.15; beta=1.40, p<.001). Among individuals with
      schizophrenia, antipsychotic medication adherence was also higher during the
      follow-up year among MyCHOIS-CommonGround users compared with the control group
      (proportion of days covered by medication, .78+/-.04 versus .69+/-.03; beta=.06,
      p<.01). CONCLUSIONS:: These findings provide new evidence that shared decision
      making tools may promote ongoing mental health treatment engagement for
      individuals with serious mental illness and improved antipsychotic medication
      adherence for those with schizophrenia.

PMID- 30286710
TI  - XenofilteR: computational deconvolution of mouse and human reads in tumor
      xenograft sequence data.
AB  - BACKGROUND: Mouse xenografts from (patient-derived) tumors (PDX) or tumor cell
      lines are widely used as models to study various biological and preclinical
      aspects of cancer. However, analyses of their RNA and DNA profiles are
      challenging, because they comprise reads not only from the grafted human cancer
      but also from the murine host. The reads of murine origin result in false
      positives in mutation analysis of DNA samples and obscure gene expression levels
      when sequencing RNA. However, currently available algorithms are limited and
      improvements in accuracy and ease of use are necessary. RESULTS: We developed the
      R-package XenofilteR, which separates mouse from human sequence reads based on
      the edit-distance between a sequence read and reference genome. To assess the
      accuracy of XenofilteR, we generated sequence data by in silico mixing of mouse
      and human DNA sequence data. These analyses revealed that XenofilteR removes >
      99.9% of sequence reads of mouse origin while retaining human sequences. This
      allowed for mutation analysis of xenograft samples with accurate variant allele
      frequencies, and retrieved all non-synonymous somatic tumor mutations.
      CONCLUSIONS: XenofilteR accurately dissects RNA and DNA sequences from mouse and
      human origin, thereby outperforming currently available tools. XenofilteR is open
      source and available at https://github.com/PeeperLab/XenofilteR .

PMID- 30286711
TI  - Developmental studies provide new insights into the evolution of sense organs in
      Sabellariidae (Annelida).
AB  - BACKGROUND: Sabellarids, also known as honeycomb or sandcastle worms, when
      building their tubes, produce chemical signals (free fatty acids) that are
      responsible for larval settlement and the formation of three-dimensional
      aggregations. The larval palps and the dorsal hump (becoming the median organ in
      adults) are presumed to participate in such a substrate selection during
      settlement. Notably, the sabellariid median organ is an apparently unique organ
      among annelids that has been attributed with a sensory function and perhaps with
      some affinities to the nuchal organs of other polychaetes. Nevertheless, detailed
      investigations of this prominent character complex including ultrastructural
      examinations are lacking so far. RESULTS: Our comprehensive investigations
      provide data about the anterior sensory organs in Sabellariidae and inform about
      their transformation during pelagic larval development. We used a comparative
      approach including immunostaining with subsequent confocal laser scanning
      microscopy (clsm), histological sections as well as electron microscopy in a
      range of larval and adult stages of two sabellariid species. We find that the
      neuronal innervation as well as the ultrastructure of the sabellariid ciliary
      structures along the median organ are highly comparable with that of nuchal
      organs known from other polychaetes. Furthermore, the myoinhibitory protein (MIP)
      - a protein known to be also involved into chemo-sensation - was detected in the
      region of the larval median organ. Moreover, we reveal the presence of an unusual
      type of photoreceptor as part of the median organ in Idanthyrsus australiensis
      with a corrugated sensory membrane ultrastructure unlike those observed in the
      segmental ocelli of other polychaetes. CONCLUSIONS: We are describing for the
      first time the nuchal organ-like structures in different developmental stages of
      two species of Sabellariidae. The external morphology, neuronal innervation,
      developmental fate and ultrastructure of the newly-discovered median organ-based
      ciliary pits are comparable with the characteristics known for annelid nuchal
      organs and therefore indicate a homology of both sensory complexes. The presence
      of myoinhibitory peptide (MIP) in the respective region supports such a
      hypothesis and exhibits the possibility of an involvement of the entire
      sabellariid median organ complex, and in particular the prominent ciliated pits,
      in chemo-sensation.

PMID- 30286712
TI  - Oldest ctenodactyloid tarsals from the Eocene of China and evolution of locomotor
      adaptations in early rodents.
AB  - BACKGROUND: Tamquammys has been considered one of the basal ctenodactyloid
      rodents, which has been documented in the earliest to middle Eocene (~ 56.0-48.5
      Ma) in China. It was the most abundant and widespread rodent genus in the Erlian
      Basin (Nei Mongol, China) and dominated Arshantan small-mammal faunas of that
      region. Here for the first time we describe the morphology of the
      astragalocalcaneal complex in Tamquammys robustus (larger) and T. wilsoni, and
      interpret it against the background of locomotor adaptations of basal
      Euarchontoglires (rodents, lagomorphs, tree shrews, and primates). RESULTS: The
      comparative morphology of the tarsal elements in Tamquammys robustus and T.
      wilsoni shows overall slenderness of the bones and their similarity to the tarsal
      elements of Rattus, a generalist species, and those of small rock squirrels (e.g.
      Sciurotamias). The two species differ slightly in their cursorial ability;
      smaller T. wilsoni shows some adaptations to climbing. The results of principal
      component analysis of the calcaneus and astragalus support this observation and
      place T. robustus in-between Rattus and ground/rock squirrel morphospace, and T.
      wilsoni closer to euarchontans, Tupaia and Purgatorius. CONCLUSIONS: The
      morphology of the tarsal elements in Tamquammys indicates a generalist rodent
      morphotype with no particular adaptations to arboreality. We suggest that
      Tamquammys as a basal ctenodactyloid is closer to the ancestral
      astragalocalcaneal morphology of rodents than that of more derived North American
      paramyines of similar age. Overall similarity in Tamquammys tarsal elements
      structure to Purgatorius, a basal primate, may point to the antiquity of the
      tarsal structure in Tamquammys and a generally unspecialized foot structure in
      early Euarchontoglires.

PMID- 30286713
TI  - GPrank: an R package for detecting dynamic elements from genome-wide time series.
AB  - BACKGROUND: Genome-wide high-throughput sequencing (HTS) time series experiments
      are a powerful tool for monitoring various genomic elements over time. They can
      be used to monitor, for example, gene or transcript expression with RNA
      sequencing (RNA-seq), DNA methylation levels with bisulfite sequencing (BS-seq),
      or abundances of genetic variants in populations with pooled sequencing (Pool
      seq). However, because of high experimental costs, the time series data sets
      often consist of a very limited number of time points with very few or no
      biological replicates, posing challenges in the data analysis. RESULTS: Here we
      present the GPrank R package for modelling genome-wide time series by
      incorporating variance information obtained during pre-processing of the HTS data
      using probabilistic quantification methods or from a beta-binomial model using
      sequencing depth. GPrank is well-suited for analysing both short and irregularly
      sampled time series. It is based on modelling each time series by two Gaussian
      process (GP) models, namely, time-dependent and time-independent GP models, and
      comparing the evidence provided by data under two models by computing their Bayes
      factor (BF). Genomic elements are then ranked by their BFs, and temporally most
      dynamic elements can be identified. CONCLUSIONS: Incorporating the variance
      information helps GPrank avoid false positives without compromising computational
      efficiency. Fitted models can be easily further explored in a browser. Detection
      and visualisation of temporally most active dynamic elements in the genome can
      provide a good starting point for further downstream analyses for increasing our
      understanding of the studied processes.

PMID- 30286714
TI  - Evaluating the social fitness Programme for older people with cognitive problems
      and their caregivers: lessons learned from a failed trial.
AB  - BACKGROUND: This process evaluation article describes the lessons learned from a
      failed trial which aimed to assess effectiveness of the tailor-made,
      multidisciplinary Social Fitness Programme to improve social participation of
      community-dwelling older people with cognitive problems (clients) and their
      caregivers (couples). METHODS: A process evaluation was performed to get insight
      in 1) the implementation of the intervention, 2) the context of intervention
      delivery from professionals' point of view, and 3) the potential impact of
      intervention delivery from participants' perspectives. Data was gathered using
      mixed-methods: questionnaires, focus group discussions, interviews, medical
      records. RESULTS: 1) Implementation. High study decline (65,3%) was mainly caused
      by a lack of internal motivation to increase social participation expressed by
      clients. 17 couples participated, however, intervention delivery was
      insufficient. 2) Context. Barriers during intervention delivery were most often
      related to client (changing needs), caregiver (increased burden) and health
      professional factors (delivery of integrated care lacked routine). 3) Impact
      Qualitative analyses revealed participants to be satisfied with intervention
      delivery, we were unable to capture these results through our primary outcome
      measure. CONCLUSIONS: This process evaluation revealed the Social Fitness study
      did not fit in three ways. First, framing the intervention on social
      participation promotion was as threatening to clients. The feeling of being
      unable to adequately contribute to social interactions seemed to be causing
      embarrassment. Second, the intervention seemed to be too complex to implement in
      the way it was designed. Third, there is a tension between the offering of a
      personalised tailor-made intervention and evaluation through a fixed study
      design. TRIAL REGISTRATION: The trial which is evaluated in this article (the
      Social Fitness study) is registered with the Dutch Trial Register (NTR), clinical
      trial number NTR4347 .

PMID- 30286715
TI  - Identification and functional characterization of intermediate-size non-coding
      RNAs in maize.
AB  - BACKGROUND: The majority of eukaryote genomes can be actively transcribed into
      non-coding RNAs (ncRNAs), which are functionally important in development and
      evolution. In the study of maize, an important crop for both humans and animals,
      aside from microRNAs and long non-coding RNAs, few studies have been conducted on
      intermediate-size ncRNAs. RESULTS: We constructed a homogenized cDNA library of
      50-500 nt RNAs in the maize inbred line Chang 7-2. Sequencing revealed 169
      ncRNAs, which contained 58 known and 111 novel ncRNAs (including 70 snoRNAs, 27
      snRNAs, 13 unclassified ncRNAs and one tRNA). Forty of the novel ncRNAs were
      specific to the Panicoideae, and 24% of them are located on sense-strand of the
      5' or 3' terminus of protein coding genes on chromosome. Target site analysis
      found that 22 snoRNAs can guide to 38 2'-O-methylation and pseudouridylation
      modification sites of ribosomal RNAs and small nuclear RNAs. Expression analysis
      showed that 43 ncRNAs exhibited significantly altered expression in different
      tissues or developmental stages of maize seedlings, eight ncRNAs had tissue
      specific expression and five ncRNAs were strictly accumulated in the early stage
      of leaf development. Further analysis showed that 3 of the 5 stage-specific
      ncRNAs (Zm-3, Zm-18, and Zm-73) can be highly induced under drought and salt
      stress, while one snoRNA Zm-8 can be repressed under PEG-simulated drought
      condition. CONCLUSIONS: We provided a genome-wide identification and functional
      analysis of ncRNAs with a size range of 50-500 nt in maize. 111 novel ncRNAs were
      cloned and 40 ncRNAs were determined to be specific to Panicoideae. 43 ncRNAs
      changed significantly during maize development, three ncRNAs can be strongly
      induced under drought and salt stress, suggesting their roles in maize stress
      response. This work set a foundation for further study of intermediate-size
      ncRNAs in maize.

PMID- 30286716
TI  - Expression of cotton PLATZ1 in transgenic Arabidopsis reduces sensitivity to
      osmotic and salt stress for germination and seedling establishment associated
      with modification of the abscisic acid, gibberellin, and ethylene signalling
      pathways.
AB  - BACKGROUND: Zinc-finger transcription factors play central roles in plant growth,
      development and abiotic stress responses. PLATZ encodes a class of plant-specific
      zinc-finger transcription factor. However, biological functions or physiological
      mechanism controlled by PLATZ are currently limited. RESULTS: GhPLATZ1
      transcripts were considerably up-regulated by NaCl, mannitol, abscisic acid (ABA)
      and gibberellin (GA) treatments. Transgenic Arabidopsis by ectopic expression of
      GhPLATZ1 exhibited faster seed germination and higher seedling establishment
      under salt and mannitol stresses than those of wild type (WT), indicating
      enhanced osmotic insensitivity in GhPLATZ1 transgenic Arabidopsis. The ABA
      content in dry seeds of GhPLATZ1 transgenic Arabidopsis was lower than that of WT
      whereas the ABA content was not changed in germinating seeds under salt stress.
      Seed germination was faster than but the seedling establishment of transgenic
      Arabidopsis was similar to WT. Besides, GhPLATZ1 transgenic and WT Arabidopsis
      exhibited insensitivity to paclobutrazol (PAC), a GA biosynthesis inhibitor,
      whereas exogenous GA could eliminate the growth difference between GhPLATZ1
      transgenic and WT Arabidopsis under salt stress. Moreover, exogenous 1
      aminocyclopropane-1-carboxylic acid (ACC), an ethylene precursor, exerted similar
      effects to GA. Furthermore, ABI4 and ETO1 transcripts were significantly down
      regulated, whereas ACS8 was up-regulated in GhPLATZ1 transgenic Arabidopsis under
      salt stress. CONCLUSIONS: In conclusion, GhPLATZ1 had broad influence in
      responses to salt and mannitol stresses in transgenic Arabidopsis during seed
      germination and seedling establishment. The effect of GhPLATZ1 expression in
      transgenic Arabidopsis might be mediated by the ABA, GA, and ethylene pathways.
      Thus, this study provided new insights into the regulatory network in response to
      abiotic stresses in plants.

PMID- 30286717
TI  - Comparative evaluation of cannabinoid receptors, apelin and S100A6 protein in the
      heart of women of different age groups.
AB  - BACKGROUND: Recent studies have shown a significant role of the endocannabinoid
      system, apelin and S100A6 protein in the regulation of cardiovascular system
      functioning. The aim of the study was to compare and evaluate the distribution of
      cannabinoid receptors (CB1 and CB2), apelin and S100A6 protein in the heart of
      healthy women in different age groups. METHODS: The study was conducted on the
      hearts of 10 women (organ donors) without a history of cardiovascular disease,
      who were divided into two age groups: women older than 50 years and women under
      50 years of age. Paraffin heart sections were processed by immunohistochemistry
      for detection of cannabinoids receptors (CB1 and CB2), apelin and S100A6 protein.
      RESULTS: CB1 and CB2 immunoreactivity in the cytoplasm of cardiomyocytes in the
      heart of women over 50 was weaker than in younger individuals. There was also
      strong immunoreactivity of CB1 in intercalated discs (ICDs) of the heart, only in
      women over 50. The presence of this receptor in this location was not found in
      women under 50. Apelin- and S100A6-immunoreactivity in the cardiomyocytes was
      stronger in older women compared to women under 50.The CB1, apelin and S100A6
      immunostaining in the endothelium of myocardial vessels was weaker in women over
      50 than in younger women, while intensity of CB2- immunoreaction in coronary
      endothelium was similar in both groups of women. The results of the study
      indicate the important role of endocannabinoids, apelin, and S100A6 protein in
      cardiac muscle function. CONCLUSION: This report might contribute to a better
      understanding of the role of endocannabinoid system, apelin and S100 proteins in
      heart function as well as shed new light on processes involved in age-related
      cardiomyopathy.

PMID- 30286718
TI  - Exploring the sensory screening experiences of nurses working in long-term care
      homes with residents who have dementia: a qualitative study.
AB  - BACKGROUND: The prevalence of vision and hearing loss is higher amongst older
      individuals with dementia, as well as higher in long-term care settings than in
      the wider community. However, the incidence of sensory impairment is
      underreported and often goes untreated. In this study, we aimed to understand
      nurses' current experiences of screening and caring for long-term care residents
      who have dementia and sensory impairment. METHODS: As part of a larger study on
      the sensory screening of long-term care residents with dementia, an environmental
      scan was conducted with front-line healthcare providers. We report here on the
      findings from the content analysis of individual, semi-structured interviews with
      nurses working in two long-term care homes in Southern Ontario, Canada. Twenty
      regulated nurses, including designated resident assessment coordinators, working
      full- or part-time with individuals who have dementia, participated across the
      two sites. All interviews were transcribed, and their contents reviewed and coded
      for themes by means of inductive thematic analysis. RESULTS: Following a
      systematic and recursive approach, three analysts identified several themes
      relating to: 1) the sensory screening process, 2) communication strategies, and
      3) quality of life, sensory loss, and dementia. Participants reported on the
      strengths and limitations of screening procedures, what improvements should be
      made, which informal strategies are effective, and the continued professional
      development that is needed. CONCLUSIONS: Nurses demonstrated insight into the
      facilitators and barriers to effective screening and care of residents with
      dementia and sensory impairments, and expressed the need for further education,
      more suitable screening tools, and formalised accountability within the screening
      process for vision and hearing loss in these long-term care residents.

PMID- 30286720
TI  - A transdisciplinary team approach to scoping reviews: the case of pediatric
      polypharmacy.
AB  - BACKGROUND: Polypharmacy can be either beneficial or harmful to children. We
      conducted a scoping review to examine the concept of pediatric polypharmacy: its
      definition, prevalence, extent and gaps in research. In this manuscript, we
      report our transdisciplinary scoping review methodology. METHODS: After
      establishing a transdisciplinary team, we iteratively developed standard
      operating procedures for the study's search strategy, inclusion/exclusion
      criteria, screening, and data extraction. We searched eight bibliographic
      databases, screened abstracts and full text articles, and extracted data from
      included studies using standardized forms. We held regular team meetings and
      performed ongoing internal validity measurements to maintain consistent and
      quality outputs. RESULTS: With the aid of EPPI Reviewer collaborative software,
      our transdisciplinary team of nine members performed dual reviews of 363 included
      studies after dual screening of 4398 abstracts and 1082 full text articles. We
      achieved overall agreement of 85% and a kappa coefficient of 0.71 (95% CI 0.68
      0.74) while screening full text articles. The screening and review processes
      required about seven hours per extracted study. The two pharmacists, an
      epidemiologist, a neurologist, and a librarian on the review team provided
      internal consultation in these key disciplines. A stakeholder group of 10 members
      with expertise in evidence synthesis, research implementation, pediatrics, mental
      health, epilepsy, pharmacoepidemiology, and pharmaceutical outcomes were
      periodically consulted to further characterize pediatric polypharmacy.
      CONCLUSIONS: A transdisciplinary approach to scoping reviews, including internal
      and external consultation, should be considered when addressing complex cross
      disciplinary questions.

PMID- 30286719
TI  - Rice stripe virus-derived siRNAs play different regulatory roles in rice and in
      the insect vector Laodelphax striatellus.
AB  - BACKGROUND: Most plant viruses depend on vector insects for transmission. Upon
      viral infection, virus-derived small interfering RNAs (vsiRNAs) can target both
      viral and host transcripts. Rice stripe virus (RSV) is a persistent-propagative
      virus transmitted by the small brown planthopper (Laodelphax striatellus, Fallen)
      and can cause a severe disease on rice. RESULTS: To investigate how vsiRNAs
      regulate gene expressions in the host plant and the insect vector, we analyzed
      the expression profiles of small RNAs (sRNAs) and mRNAs in RSV-infected rice and
      RSV-infected planthopper. We obtained 88,247 vsiRNAs in rice that were
      predominantly derived from the terminal regions of the RSV RNA segments, and
      351,655 vsiRNAs in planthopper that displayed relatively even distributions on
      RSV RNA segments. 38,112 and 80,698 unique vsiRNAs were found only in rice and
      planthopper, respectively, while 14,006 unique vsiRNAs were found in both of
      them. Compared to mock-inoculated rice, 273 genes were significantly down
      regulated genes (DRGs) in RSV-infected rice, among which 192 (70.3%) were
      potential targets of vsiRNAs based on sequence complementarity. Gene ontology
      (GO) analysis revealed that these 192 DRGs were enriched in genes involved in
      kinase activity, carbohydrate binding and protein binding. Similarly, 265 DRGs
      were identified in RSV-infected planthoppers, among which 126 (47.5%) were
      potential targets of vsiRNAs. These planthopper target genes were enriched in
      genes that are involved in structural constituent of cuticle, serine-type
      endopeptidase activity, and oxidoreductase activity. CONCLUSIONS: Taken together,
      our results reveal that infection by the same virus can generate distinct vsiRNAs
      in different hosts to potentially regulate different biological processes, thus
      reflecting distinct virus-host interactions.

PMID- 30286721
TI  - Genome-wide identification and differentially expression analysis of lncRNAs in
      tilapia.
AB  - BACKGROUND: Long noncoding RNAs (LncRNAs) play important roles in fundamental
      biological processes. However, knowledge about the genome-wide distribution and
      stress-related expression of lncRNAs in tilapia is still limited. RESULTS: Genome
      wide identification of lncRNAs in the tilapia genome was carried out in this
      study using bioinformatics tools. 103 RNAseq datasets that generated in our
      laboratory or collected from NCBI database were analyzed. In total, 72,276 high
      confidence lncRNAs were identified. The averaged positive correlation coefficient
      (r_mean = 0.286) between overlapped lncRNA and mRNA pairs showed significant
      differences with the values for all lncRNA-mRNA pairs (r_mean = 0.176, z
      statistics = - 2.45, p value = 0.00071) and mRNA-mRNA pairs (r_mean = 0.186, z
      statistics = - 2.23, p value = 0.0129). Weighted correlation network analysis of
      the lncRNA and mRNA datasets from 12 tissues identified 21 modules and many
      interesting mRNA genes that clustered with lncRNAs. Overrepresentation test
      indicated that these mRNAs enriched in many biological processes, such as meiosis
      (p = 0.00164), DNA replication (p = 0.00246), metabolic process (p = 0.000838)
      and in molecular function, e.g., helicase activity (p = 0.000102) and catalytic
      activity (p = 0.0000612). Differential expression (DE) analysis identified 99
      stress-related lncRNA genes and 1955 tissue-specific DE lncRNA genes. MiRNA
      lncRNA interaction analysis detected 72,267 lncRNAs containing motifs with
      sequence complementary to 458 miRNAs. CONCLUSIONS: This study provides an
      invaluable resource for further studies on molecular bases of lncRNAs in tilapia
      genomes. Further function analysis of the lncRNAs will help to elucidate their
      roles in regulating stress-related adaptation in tilapia.

PMID- 30286722
TI  - Estimating bacteria diversity in different organs of nine species of mosquito by
      next generation sequencing.
AB  - BACKGROUND: Symbiosis in insects is accumulating significant amount of studies:
      the description of a wide array of mutualistic associations across the
      evolutionary history of insects suggests that resident microbiota acts as a
      driving force by affecting several aspects of hosts biology. Among arthropods,
      mosquito midgut microbiota has been largely investigated, providing crucial
      insights on the role and implications of host-symbiont relationships. However,
      limited amount of studies addressed their efforts on the investigation of
      microbiota colonizing salivary glands and reproductive tracts, crucial organs for
      pathogen invasion and vertical transmission of symbiotic microorganisms. Using
      16S rRNA gene sequencing-based approach, we analysed the microbiota of gut,
      salivary glands and reproductive tracts of several mosquito species, representing
      some of the main vectors of diseases, aiming at describing the dynamics of
      bacterial communities within the individual. RESULTS: We identified a shared core
      microbiota between different mosquito species, although interesting inter- and
      intra-species differences were detected. Additionally, our results showed deep
      divergences between genera, underlining microbiota specificity and adaptation to
      their host. CONCLUSIONS: The comprehensive landscape of the bacterial microbiota
      components may ultimately provide crucial insights and novel targets for possible
      application of symbionts in innovative strategies for the control of vector borne
      diseases, globally named Symbiotic Control (SC), and suggesting that the
      holobiont of different mosquito species may significantly vary. Moreover,
      mosquito species are characterized by distinctive microbiota in different organs,
      likely reflecting different functions and/or adaptation processes.

PMID- 30286723
TI  - ROK study-C (Rainbow of KIBOU study-colorectum): a colorectal cancer survivor
      cohort study on food, nutrition, physical activity, psychosocial factors and its
      influences on colorectal cancer recurrence, survival and quality of life in
      Japan.
AB  - BACKGROUND: Many studies have shown that lifestyle factors such as diet, physical
      activity are related to the incidence of cancer. However, there are few studies
      on the association between lifestyle factors and cancer prognosis. To investigate
      the influence of lifestyle factors and psychosocial factors on prognosis, we
      started a prospective study of women with breast cancer, the Rainbow of KIBOU
      study-Breast (ROK Study-B) in 2007. As of February 2018, more than 6300 women
      have been enrolled, thus making this one of the world's largest cancer patient
      cohort studies. Based on the know-how obtained from this study, we started
      another new cohort study for colorectal cancer patient (ROK Study-C). METHODS:
      The ROK Study-C is a prospective observational study for colorectal cancer
      survivors at the National Cancer Center Hospital. Participants fill in several
      self-administrated questionnaires about lifestyle, psychosocial factors
      (including posttraumatic growth and benefit finding, support), and quality of
      life (QOL) 5 times in total: at diagnosis, 3 and 6 months, 1 and 5 years after
      surgery. CT-scans will be collected to assess body composition and obesity. We
      also use blood and cancer tissue from the Biobank. The primary endpoint is
      disease-free survival. The secondary endpoints are overall survival and health
      related QOL. The planned sample size is 2000 and the follow-up period is 5 years
      after the last enrollment. DISCUSSION: Recruitment began in December 2015 and the
      study is still ongoing. The ROK Study-C will contribute to improvements in
      patient prognosis and yield important evidence for colorectal cancer
      survivorship.

PMID- 30286724
TI  - Dynapenia could predict chemotherapy-induced dose-limiting neurotoxicity in
      digestive cancer patients.
AB  - BACKGROUND: FIGHTDIGO study showed the feasibility and acceptability of handgrip
      strength (HGS) measure in routine in 201 consecutive patients with digestive
      cancer treated with ambulatory chemotherapy. The present study focuses on the
      second aim of FIGHTDIGO study: the relationships between pre-therapeutic
      dynapenia and chemotherapy-induced Dose-Limiting Toxicities (DLT). METHODS: In
      this ancillary prospective study, DLT were analyzed in a sub-group of 45
      chemotherapy-naive patients. Two bilateral consecutive measures of HGS were
      performed with a Jamar dynamometer before the first cycle of chemotherapy.
      Dynapenia was defined as HGS < 30 kg (men) and < 20 kg (women). DLT and/or Dose
      Limiting Neurotoxicity (DLN) were defined as any toxicity leading to dose
      reduction, treatment delays or permanent treatment discontinuation. RESULTS: Two
      thirds of chemotherapies were potentially neurotoxic (n = 31 [68.7%]) and 22
      patients (48.9%) received FOLFOX (5FU, leucovorin plus oxaliplatin) regimen
      chemotherapy. Eleven patients (24.4%) had pre-therapeutic dynapenia. The median
      number of chemotherapy cycles was 10 with a median follow-up of 167 days. Twenty
      two patients experienced DLT (48.9%). There was no significant association
      between pre-therapeutic dynapenia and DLT (p = 0.62). Nineteen patients (42.2%)
      experienced DLN. In multivariate analysis, dynapenia and tumoral location
      (stomach, biliary tract or small intestine) were independent risk factors for DLN
      (HR = 3.5 [1.3; 9.8]; p = 0.02 and HR = 3.6 [1.3; 10.0]; p = 0.01, respectively).
      CONCLUSIONS: Digestive cancer patients with pre-therapeutic dynapenia seemed to
      experience more DLN. HGS routine measurement may be a way to screen patients with
      frailty marker (dynapenia) who would require chemotherapy dose adjustment and
      adapted physical activity programs. TRIAL REGISTRATION: NCT02797197 June 13, 2016
      retrospectively registered.

PMID- 30286725
TI  - Molecular characteristics of extended-spectrum beta-lactamase-producing
      Escherichia coli isolated from the rivers and lakes in Northwest China.
AB  - BACKGROUND: Extended-spectrum beta-lactamases (ESBLs)-producing Escherichia coli
      (E. coli) isolates in environment water become progressively a potential threat
      to public health, while the detailed information about the ESBL-producing E. coli
      isolates in the rivers and lakes in Northwest China is scarce. In the present
      study, it was aimed to characterize the ESBL-producing E. coli isolated from the
      surface waters in Northwest China. RESULTS: A total of 2686 E. coli isolates were
      obtained from eleven rivers and lakes in Northwest China to screen for ESBL
      producers. Seventy-six (2.8%) isolates were classified as ESBL producers, and
      phylogenic groups D and A accounted for 59.2% of the ESBL producers. CTX-Ms were
      the predominant ESBLs genotype, and they were represented by seven blaCTX-M
      subtypes. blaCTX-M-14 was the most prevalent specific CTX-M gene, followed by
      blaCTX-M-9, blaCTX-M-123, blaCTX-M-15, blaCTX-M-27, blaCTX-M-1 and blaCTX-M-65.
      Moreover, 54 of the 76 ESBL producers carried at least one plasmid-mediated
      quinolone resistance (PMQR) gene, and aac(6')-Ib-cr was predominant. The overall
      occurrence of virulence factors ranged from 1.3% (eae) to 48.7% (traT). Thirty
      seven sequence types (STs) were confirmed among the 76 ESBL producers, and the
      predominant was ST10, which was represented by 10 isolates; importantly, clone B2
      ST131, associated with severe infections in humans and animals, was detected
      three times. CONCLUSION: The prevalence of ESBL-producing E. coli from the rivers
      and lakes in Northwest China was low (2.8%), and the extraintestinal pathogenic
      E. coli (ExPEC) pathotype was the most commonly detected on the basis of the
      virulence factor profiles. 76.3% of ESBL producers harbored more than one beta
      lactamase gene, and blaCTX-M-14 was the predominant genotype. Notably, one ST131
      isolate from Gaogan Canal simultaneously harbored blaCTX-M-9, blaCTX-M-15, blaCTX
      M-123, blaKPC-2, blaNDM-1, blaOXA-2 as well as the PMQR genes qnrA, qnrS and
      aac(6')-Ib-cr.

PMID- 30286726
TI  - Impact of the 10-valent pneumococcal conjugate vaccine on antimicrobial
      prescriptions in young children: a whole population study.
AB  - BACKGROUND: Antimicrobial resistance is a public-health threat and antimicrobial
      consumption is the main contributor. The ten-valent pneumococcal conjugate
      vaccine (PHiD-CV10) was introduced into the Icelandic vaccination program in
      2011. The aim was to estimate the vaccine impact of PHiD-CV10 on outpatient
      antimicrobial prescriptions in children. METHODS: Eleven Icelandic birth-cohorts
      (2005-2015) were followed from birth until three years of age or to the end of
      the study period (December 31, 2016). Birth-cohorts were grouped as vaccine non
      eligible (VNEC, 2005-2010) or vaccine eligible (VEC, 2011-2015). Data on primary
      care visits for respiratory infections and antimicrobial prescriptions were
      extracted from two national registers. Using national identification numbers,
      prescriptions were linked to physician visits if filled within three days of the
      visit. Incidence rates and incidence rate ratios between VNEC and VEC were
      calculated. An Andersen-Gill model was used to model the individual level data,
      accounting for repeated events and censoring. Vaccine impact was calculated as (1
      - Hazard Ratio) * 100%. RESULTS: Included were 53,510 children who contributed
      151,992 person-years of follow-up and filled 231,660 antimicrobial prescriptions.
      The incidence rate was significantly lower in the VEC compared to the VNEC, 144.5
      and 157.2 prescriptions per 100 person-years respectively (IRR 0.92, 95%CI 0.91
      0.93). Children in VEC were more likely to have filled zero (IRR 1.16 (95%CI 1.10
      1.23) and 1-4 (IRR 1.08 95%CI 1.06-1.11) prescriptions compared to children in
      VNEC. The vaccine impact of PHiD-CV10 against all-cause antimicrobial
      prescriptions was 5.8% (95%CI 1.6-9.8%).When only considering acute otitis media
      associated prescriptions, the vaccine impact was 21.8% (95%CI 11.5-30.9%).
      CONCLUSION: The introduction of PHiD-CV10 lead to reduced antimicrobial use in
      children, mainly by reducing acute otitis media episodes. This intervention
      therefore reduces both disease burden and could slow the spread of antimicrobial
      resistance.

PMID- 30286727
TI  - Disability, quality of life and all-cause mortality in older Mexican adults:
      association with multimorbidity and frailty.
AB  - BACKGROUND: Multimorbidity and frailty are relevant conditions among older adult
      population. There is growing evidence about their association with poor health
      outcomes like disability, worst quality of life, and death. Nonetheless, the
      independent associations of both conditions have been studied, and few evidence
      exists about an interaction between them. Our aims were to assess the association
      of frailty and multimorbidity with the disability, quality of life and all-cause
      mortality as well as to analyze a potential interaction between these conditions.
      METHODS: Analytical samples included 1410 respondents for disability and quality
      of life, and 1792 for mortality. We performed a longitudinal analysis with older
      Mexican adults aged 50, using data collected from the WHO's Study on global
      AGEing and Adult Health Waves 1 and 2. Disability was measured using the World
      Health Organization Disability Assessment Schedule (WHODAS 2.0), and quality of
      life using the WHOQOL (WHO Quality of Life) instrument. All-cause mortality was
      determined by reviewing death certificates. Associations of frailty and
      multimorbidity with disability, quality of life and mortality were estimated
      using linear regression and Cox proportional hazards models. RESULTS:
      Multimorbidity assessed through three patterns (cardiopulmonary, vascular
      metabolic, and mental-musculoskeletal) was associated with the three outcomes in
      this study. Cardiopulmonary and mental-musculoskeletal patterns increased the
      WHODAS mean score (beta = 5.05; p < 0.01 and beta = 5.10; p < 0.01, respectively)
      and decreased WHOQOL score (beta = - 1.81; p < 0.01 and beta = - 2.99; p < 0.01,
      respectively). Vascular-metabolic was associated with mortality (HR = 1.47; p =
      0.04), disability (beta = 3.27; p < 0.01) and quality of life (beta = - 1.30; p =
      0.02). Frailty was associated with mortality (pre-frail: HR = 1.48; p = 0.02 and
      frail: HR = 1.68; p = 0.03), disability (pre-frail: beta = 5.02; p < 0.01; frail:
      beta = 13.29; p < 0.01) and quality of life (pre-frail: beta = - 2.23; p < 0.01;
      frail: beta = - 4.38; p < 0.01). Interaction terms of frailty and multimorbidity
      were not statistically significant. CONCLUSIONS: Multimorbidity and frailty are
      important predictors of poor health outcomes. These results highlight the
      importance of carrying out health promotion and prevention actions as well as
      specific interventions aimed at older adults who suffer from multimorbidity and
      frailty, in such a way that deleterious effects on health can be avoided.

PMID- 30286728
TI  - SoLAT (Sorafenib Lenvatinib alternating treatment): a new treatment protocol with
      alternating Sorafenib and Lenvatinib for refractory thyroid Cancer.
AB  - BACKGROUND: In the last decade, several tyrosine kinase inhibitors (TKIs), which
      disrupt pathways involved in the proliferation and tumorigenesis of thyroid
      cancer, have been extensively studied. Two different TKIs, lenvatinib and
      sorafenib, were recently approved by both the US FDA and European Medicine
      Agency. Until date, the duration of the TKI response is not sufficient and
      resistance eventually occurs. The goal of this study was to investigate a new
      treatment protocol, SoLAT, using sorafenib and lenvatinib alternatively on
      refractory thyroid cancer. METHODS: Patient-derived aggressive papillary thyroid
      cancer (PTC) cell lines from patients with biochemical and histologically proven
      aggressive RAI-refractory papillary thyroid cancer were exposed to sorafenib and
      lenvatinib alternatively. Human thyroid cancer cell xenografts were obtained by
      injecting patient-derived aggressive PTC cell lines into the flank of female
      BALB/c nude mice. Tumor-bearing mice were treated with sorafenib and lenvatinib
      alternatively. Cell viability assay, immunofluorescence analysis, confocal
      imaging, immunoblot analysis, flow cytometry analysis of cell cycle and a tube
      formation assay were performed. RESULTS: SoLAT was more effective for advanced
      PTC cell lines than individual treatment. Immunoblot analysis showed that SoLAT
      markedly increased levels of cell cycle inhibitors (p53 and p21), and pro
      apoptotic factors (Apaf-1 and cleaved caspase 3) and decreased levels of positive
      cell cycle regulators (cyclin D1, CDK4, CDK6) and anti-apoptotic factors (p
      NFkappaB, Bcl-2). Increased sub-G0/G1 population was observed in the SoLAT group,
      leading to apoptosis, cell cycle arrest, and strong inhibition of advanced PTC
      cell viability. SoLAT reduced the level of EMT markers such as vimentin, E
      cadherin, Snail and Zeb1 by FGFR inhibition. In the xenograft model, individual
      treatment with sorafenib or lenvatinib did not markedly suppress patient-derived
      aggressive PTC cell xenograft tumors, whereas SoLAT significantly suppressed the
      proliferation of these tumors. CONCLUSIONS: SoLAT was more effective than
      individual treatment with sorafenib or lenvatinib in inhibiting PTC progression
      by inducing cell cycle arrest. Studies using both in vitro cell culture and an in
      vivo xenograft model provided evidence of tumor shrinkage with SoLAT. We suggest
      that these effects may be due to reduced EMT-mediated drug resistance in the
      aggressive PTC model.

PMID- 30286729
TI  - Uc.416 + A promotes epithelial-to-mesenchymal transition through miR-153 in renal
      cell carcinoma.
AB  - BACKGROUND: The transcribed ultraconserved regions (T-UCRs) are a novel class of
      non-coding RNAs that are absolutely conserved across species and are involved in
      carcinogenesis in some cancers. However, the expression and biological role of T
      UCRs in renal cell carcinoma (RCC) remain poorly understood. This study aimed to
      examine the expression and functional role of Uc.416 + A and analyze the
      association between Uc.416 + A and epithelial-to-mesenchymal transition in RCC.
      METHODS: Expression of Uc.416 + A in 35 RCC tissues, corresponding normal kidney
      tissues and 13 types of normal tissue samples was determined by quantitative
      reverse transcription-polymerase chain reaction (qRT-PCR). We performed a cell
      growth and migration assay in RCC cell line 786-O transfected with negative
      control and siRNA for Uc.416 + A. We evaluated the relation between Uc.416 + A
      and miR-153, which has a complimentary site of Uc.416 + A. RESULTS: qRT-PCR
      analysis revealed that the expression of Uc.416 + A was higher in RCC tissues
      than that in corresponding normal kidney tissues. Inhibition of Uc.416 + A
      reduced cell growth and cell migration activity. There was an inverse correlation
      between Uc.416 + A and miR-153. Western blot analysis showed Uc.416 + A modulated
      E-cadherin, vimentin and snail. The expression of Uc.416 + A was positively
      associated with the expression of SNAI1, VIM and inversely associated with the
      expression of CDH1. CONCLUSIONS: The expression of Uc.416 + A was upregulated in
      RCC and especially in RCC tissues with sarcomatoid change. Uc.416 + A promoted
      epithelial-to-mesenchymal transition through miR-153. These results suggest that
      Uc.416 + A may be a promising therapeutic target.

PMID- 30286730
TI  - High cut-off membrane for in-vivo dialysis of free plasma hemoglobin in a patient
      with massive hemolysis.
AB  - BACKGROUND: The possibility of clearing Cell-free Plasma Hemoglobin (CPH) from
      human plasma may appear attractive, especially when considering the noxious
      effects that CPH has on the immune function and the renal damage caused by its
      filtration. The existence of the so-called High Cut-Off (HCO) filters, possessing
      pores as big as 60 kDa, could potentially allow the clearance of the alphabeta
      dimers (31.3 kDa), the form in which the alpha2beta2 hemoglobin tetramers (62.6
      kDa) physiologically dissociate in plasma. We present herein the first reported
      case in which such an attempt was made. CASE PRESENTATION: The patient was a 51
      year-old man with hemolytic crisis due to glucose-6-phosphate dehydrogenase
      deficiency, further complicated by pigment-induced nephropathy. He underwent a 48
      h CVVHD session, in which a HCO filter was used. The Sieving Coefficient (SC) for
      CPH was initially 0.08 and decreased to 0.02 after 24 h. This unexpected low SC
      was due to the initial high concentration of CPH (4.24 g/L). At such
      concentrations, the alpha2beta2 tetramer poorly dissociates into the alphabeta
      dimer; but increases exponentially at concentrations lower than 1 g/L.
      CONCLUSIONS: Clearance of CPH through a HCO filter is technically feasible but
      its performance markedly relies on the initial concentration of CPH. Critically
      ill patients with smoldering hemolysis, as it happens during septic shock or ECMO
      treatment, may benefit the most from the use of this membrane in order to clear
      CPH.

PMID- 30286731
TI  - Development of membranoproliferative glomerulonephritis-like glomerulopathy in a
      patient with neutrophilia resulting from endogenous granulocyte-colony
      stimulating factor overproduction: a case report.
AB  - BACKGROUND: The pathophysiologic role of exogenous granulocyte-colony stimulating
      factor (G-CSF) administration is reportedly linked to the progression of
      glomerulonephritis. However, the relationship between endogenous G-CSF
      overproduction and the progression of glomerulopathy has not been well
      investigated. CASE PRESENTATION: A 76-year-old woman presented with neutrophilia
      at a medical check-up and thorough examination revealed a high level of serum G
      CSF. She subsequently developed mild renal dysfunction and proteinuria. Her renal
      biopsy showed lobulation of the glomeruli with mesangial proliferation and
      glomerular capillary walls with a double contour but no immune complex
      deposition, suggesting membranoproliferative glomerulonephritis-like
      glomerulopathy. Thereafter, her proteinuria levels fluctuated in parallel with
      the changes in her blood neutrophil count and finally reduced considerably in
      association with her decreased neutrophil count. CONCLUSIONS: The unique features
      of this case suggest that endogenous overproduction of G-CSF could play an
      important role in the pathogenesis of active glomerulonephritis.

PMID- 30286732
TI  - Cerebral infarction associated with benign mucin-producing adenomyosis: report of
      two cases.
AB  - BACKGROUND: Cerebral infarction associated with a malignant tumor is widely
      recognized as Trousseau syndrome. In contrast, few cases of cerebral infarction
      associated with benign tumors have been reported. We present two cases of embolic
      stroke that seemed to be caused by mucin-producing adenomyosis. CASE
      PRESENTATION: The patients were women aged 42 and 50 years old. Both patients
      developed right hemiparesis and aphasia, and cerebral infarctions were detected
      in the left cerebral hemisphere. There were no other abnormal findings, except
      for elevation of CA125 and D-dimer. Trousseau syndrome was suspected in both
      cases, but whole body examinations did not reveal any malignant tumors. However,
      uterine adenomyosis was detected in both patients. CONCLUSIONS: From our findings
      and a review of the literature, both mucin-producing malignant tumors and mucin
      producing benign tumors such as adenomyosis may cause hypercoagulability and
      cerebral infarction. This mechanism should be considered in a case of a young to
      middle-aged woman with embolic stroke of an undetermined origin.

PMID- 30286733
TI  - Patients' quality of life during active cancer treatment: a qualitative study.
AB  - BACKGROUND: Patients' quality of life has become a major objective of care in
      oncology. At the same time, it has become the object of increasing interest by
      researchers, working with both quantitative and qualitative methods. Progress in
      oncology has enabled more patients to survive longer, so that cancer is
      increasingly often a chronic disease that requires long-term treatment that can
      have negative effects on patients' quality of daily life. Nonetheless, no
      qualitative study has explored what patients report affects their quality of
      daily life during the treatment period. This study is intended to fill this gap.
      METHODS: We conducted a multicenter qualitative study based on 30 semi-structured
      interviews. Participants, purposively selected until data saturation, had diverse
      types of cancer and had started treatment at least 6 months before interview.
      Data were examined by thematic analysis. RESULTS: Our analysis found two themes:
      (1) what negatively affected for patient's quality of daily life during the
      treatment period, a question to which patients responded by talking only about
      the side effects of treatment; and (2) what positively affected their quality of
      daily life during the treatment period with three sub-themes: (i) The interest in
      having -investing in - a support object that can be defined as an object, a
      relationship or an activity particularly invested by the patients which makes
      them feel good and makes the cancer and its treatment bearable, (ii)The
      subjective perception of the efficacy of the antitumor treatment and (iii) the
      positive effects of relationships, with friends and family, and also with their
      physician. CONCLUSIONS: Patients must be involved in their care if they are to be
      able to bear their course of treatment and find ways to endure the difficult
      experience of cancer care. The support object represents an important therapeutic
      lever that can be used by their oncologists. They should be interested in their
      support objects, in order to support the patients in this investment and to help
      them to maintain it throughout the health care pathway. Furthermore, showing
      interest in this topic, important to the patient, could improve the physician
      patient relation without using up very much of the physician's time.

PMID- 30286735
TI  - The landscape of vaccines in China: history, classification, supply, and price.
AB  - BACKGROUND: Vaccine regulation in China meets World Health Organization
      standards, but China's vaccine industry and immunization program have some
      characteristics that differ from other countries. We described the history,
      classification, supply and prices of vaccines available and used in China,
      compared with high-and middle-incomes countries to illustrate the development of
      Chinese vaccine industry and immunization program. METHODS: Immunization policy
      documents were obtained from the State Council and the National Health and Family
      Planning Commission (NHFPC). Numbers of doses of vaccines released in China were
      obtained from the Biologicals Lot Release Program of the National Institutes for
      Food and Drug Control (NIFDC). Vaccine prices were obtained from Chinese Central
      Government Procurement (CCGP). International data were collected from US CDC,
      Public Health England, European CDC, WHO, and UNICEF. RESULTS: Between 2007 and
      2015, the annual supply of vaccines in China ranged between 666 million and 1,190
      million doses, with most doses produced domestically. The government's Expanded
      Program on Immunization (EPI) prevents 12 vaccine preventable diseases (VPD)
      through routine immunization. China produces vaccines that are in common use
      globally; however, the number of routinely-prevented diseases is fewer than in
      high- and middle-income countries. Contract prices for program (EPI) vaccines
      ranged from 0.1 to 5.7 US dollars per dose - similar to UNICEF prices. Contract
      prices for private-market vaccines ranged from 2.4 to 102.9 US dollars per dose -
      often higher than prices for comparable US, European, and UNICEF vaccines.
      CONCLUSION: China is a well-regulated producer of vaccines, but some vaccines
      that are important globally are not included in China's EPI system in China.
      Sustained and coordinated effort will be required to bring Chinese vaccine
      industry and EPI into an era of global leadership.

PMID- 30286734
TI  - Women suffer more from disrespectful and abusive care than from the labour pain
      itself: a qualitative study from Women's perspective.
AB  - BACKGROUND: Utilization of institutional delivery services could be hampered by
      women's experience of disrespectful and abusive care during childbirth. However,
      such experiences are not well documented and taken into consideration id planning
      maternal health services in many developing countries. The aim of this study was
      to describe women's experience of disrespect and abuse during giving birth at
      health facilities in northern Ethiopia. METHODS: A qualitative phenomenological
      study was conducted in Tigray, Ethiopia. Focus group discussions (FGDs) with
      primipara and multipara women were conducted to collect the necessary
      information. All study participants had their last delivery at a health facility
      in the year preceding the study. A semi-structured discussion guide was used to
      elicit discussion. Discussions were audio recorded and transcribed verbatim in
      the local language and then translated to English. Data were analyzed using
      thematic analysis approach assisted by the Open Code qualitative data management
      software. RESULTS: The study participants described disrespect and abuse as
      serious obstacles to utilization of maternal health services. Women reported
      experiencing feelings of being infantilized, losing self-control, being
      overlooked, being informed bad news without proper preparation, repeated
      examination without being properly communicated/informed, disallow companions,
      and left unattended during labor. Facility related issues include women's
      perception of incompetence of professionals attending delivery, unhygienic
      facilities, and unavailability of basic supplies. CONCLUSION: Women consider
      health facilities not fully prepared to provide respectful maternal care.
      Sustainable increase in institutional delivery requires ensuring quality,
      compassionate and caring services in all health facilities.

PMID- 30286736
TI  - Isolated optic neuritis with a concurrent abnormal trigeminal nucleus on imaging:
      case report of a rare complication of herpes zoster ophthalmicus.
AB  - BACKGROUND: Herpes zoster ophthalmicus (HZO) is an inflammation related to
      reactivation of the latent varicella zoster virus (VZV), involving the ophthalmic
      branch of the trigeminal nerve. Optic neuritis (ON), a rare ocular complication
      following HZO, has been reported in 1.9% of HZO-affected eyes. Most previous
      cases occurred simultaneously with other ocular complications, especially orbital
      apex syndrome. Moreover, detailed magnetic resonance imaging (MRI) with diffusion
      weighted imaging of the optic nerve and trigeminal nucleus in HZO-related ON has
      been rarely reported. We report a case of postherpetic isolated ON with a
      concurrent abnormal trigeminal nucleus on imaging. CASE PRESENTATION: A healthy
      58-year-old female presented with sudden painful visual loss in her right eye for
      2 days. Four weeks before the presentation, her right eye was diagnosed with HZO,
      and she received intravenous acyclovir for 10 days. Ophthalmic examination
      revealed a visual acuity of light perception and 20/20 in the right and left
      eyes, respectively. A relative afferent pupillary defect was present in the right
      eye. Neurological examination was significant for hypoesthesia in the area of the
      HZO. A clinical diagnosis of HZO-related right retrobulbar ON was made, and other
      causes of atypical ON were excluded. MRI showed enhancement and restricted
      diffusion of the right-sided optic nerve with linear hyperintense T2 of the right
      sided spinal trigeminal nucleus and tract (STNT) along the brainstem. She
      received 14 days of intravenous acyclovir and 5 days of methylprednisolone. Both
      were switched to an oral route for 2 months. After the completion of treatment,
      the visual acuity was counting fingers and 20/20 in the right eye and left eye,
      respectively. Stable brainstem STNT abnormalities and resolution of ON were found
      radiologically. CONCLUSIONS: Isolated ON is a rare ocular complication following
      HZO. An abnormal high signal of STNT on a T2 weighted image may be present, which
      may be a clue for VZV-associated complications, such as HZO-related ON,
      especially in cases lacking an obvious history of HZO or other concomitant ocular
      complications. Prompt treatment with both acyclovir and corticosteroids should be
      started. Restricted diffusion of the optic nerve may be a predictor for poor
      visual recovery.

PMID- 30286738
TI  - Comment on "report of 5 novel mutations of the alpha-L-iduronidase gene and
      comparison of Korean mutations in relation with those of Japan or China in
      patients with mucopolysaccharidosis I".
AB  - In this comment, we highlight that the IDUA pathogenic variants 704ins5 and
      c.613_617dupTGCTC are the same, but have different names depending on the
      nomenclature guideline used. Therefore, the frequency of this variant is 17.6% of
      alleles in Korean patients. This commentary stresses the importance of proper
      variant annotation and the use of guidelines when describing or reviewing
      mutations.

PMID- 30286737
TI  - Acceptability of HIV self-testing to support pre-exposure prophylaxis among
      female sex workers in Uganda and Zambia: results from two randomized controlled
      trials.
AB  - BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is highly effective for
      prevention of HIV acquisition, but requires HIV testing at regular intervals.
      Female sex workers (FSWs) are a priority population for HIV prevention
      interventions in many settings, but face barriers to accessing healthcare. Here,
      we assessed the acceptability of HIV self-testing for regular HIV testing during
      PrEP implementation among FSWs participating in a randomized controlled trial of
      HIV self-testing delivery models. METHODS: We used data from two HIV self-testing
      randomized controlled trials with identical protocols in Zambia and in Uganda.
      From September-October 2016, participants were randomized in groups to: (1)
      direct delivery of an HIV self-test, (2) delivery of a coupon, exchangeable for
      an HIV self-test at nearby health clinics, or (3) standard HIV testing services.
      Participants completed assessments at baseline and 4 weeks. Participants
      reporting their last HIV test was negative were asked about their interest in
      various PrEP modalities and their HIV testing preferences. We used mixed effects
      logistic regression models to measure differences in outcomes across
      randomization arms at four weeks. RESULTS: At 4 weeks, 633 participants in Zambia
      and 749 participants in Uganda reported testing negative at their last HIV test.
      The majority of participants in both studies were "very interested" in daily oral
      PrEP (91% Zambia; 66% Uganda) and preferred HIV self-testing to standard testing
      services while on PrEP (87% Zambia; 82% Uganda). Participants in the HIV self
      testing intervention arms more often reported preference for HIV self-testing
      compared to standard testing services to support PrEP in both Zambia (P = 0.002)
      and Uganda (P < 0.001). CONCLUSION: PrEP implementation programs for FSW could
      consider inclusion of HIV self-testing to reduce the clinic-based HIV testing
      burden. TRIAL REGISTRATION: ClinicalTrials.gov NCT02827240 and NCT02846402 .

PMID- 30286740
TI  - Automatic differentiation of Glaucoma visual field from non-glaucoma visual filed
      using deep convolutional neural network.
AB  - BACKGROUND: To develop a deep neural network able to differentiate glaucoma from
      non-glaucoma visual fields based on visual filed (VF) test results, we collected
      VF tests from 3 different ophthalmic centers in mainland China. METHODS: Visual
      fields obtained by both Humphrey 30-2 and 24-2 tests were collected. Reliability
      criteria were established as fixation losses less than 2/13, false positive and
      false negative rates of less than 15%. RESULTS: We split a total of 4012 PD
      images from 1352 patients into two sets, 3712 for training and another 300 for
      validation. There is no significant difference between left to right ratio (P =
      0.6211), while age (P = 0.0022), VFI (P = 0.0001), MD (P = 0.0039) and PSD (P =
      0.0001) exhibited obvious statistical differences. On the validation set of 300
      VFs, CNN achieves the accuracy of 0.876, while the specificity and sensitivity
      are 0.826 and 0.932, respectively. For ophthalmologists, the average accuracies
      are 0.607, 0.585 and 0.626 for resident ophthalmologists, attending
      ophthalmologists and glaucoma experts, respectively. AGIS and GSS2 achieved
      accuracy of 0.459 and 0.523 respectively. Three traditional machine learning
      algorithms, namely support vector machine (SVM), random forest (RF), and k
      nearest neighbor (k-NN) were also implemented and evaluated in the experiments,
      which achieved accuracy of 0.670, 0.644, and 0.591 respectively. CONCLUSIONS: Our
      algorithm based on CNN has achieved higher accuracy compared to human
      ophthalmologists and traditional rules (AGIS and GSS2) in differentiation of
      glaucoma and non-glaucoma VFs.

PMID- 30286739
TI  - Population-based phase II trial of stereotactic ablative radiotherapy (SABR) for
      up to 5 oligometastases: SABR-5.
AB  - BACKGROUND: Oligometastases refer to a state of disease where cancer has spread
      beyond the primary site, but is not yet widely metastatic, often defined as 1-3
      or 1-5 metastases in number. Stereotactic ablative radiotherapy (SABR) is an
      emerging radiotherapy technique to treat oligometastases that require further
      prospective population-based toxicity estimates. METHODS: This is a non
      randomized phase II trial where all participants will receive experimental SABR
      treatment to all sites of newly diagnosed or progressing oligometastatic disease.
      We will accrue 200 patients to assess toxicity associated with this experimental
      treatment. The study was powered to give a 95% confidence on the risk of late
      grade 4 toxicity, anticipating a < 5% rate of grade 4 toxicity. DISCUSSION: SABR
      treatment of oligometastases is occurring off-trial at a high rate, without
      sufficient evidence of its efficacy or toxicity. This trial will provide
      necessary toxicity data in a population-based cohort, using standardized doses
      and organ at risk constraints, while we await data on efficacy from randomized
      phase III trials. TRIAL REGISTRATION: Registered through clinicaltrials.gov
      NCT02933242 on October 14, 2016 prospectively before patient accrual.

PMID- 30286742
TI  - Introduction of safety and quality standards for private health care providers: a
      case-study from the Republic of Srpska, Bosnia and Herzegovina.
AB  - BACKGROUND: Regulation of private health care providers (PHPs) in middle-income
      countries can be challenging. Mandatory safety and quality standards for PHPs
      have been in place in the Republic of Srpska since 2012, but not all PHPs have
      adopted them yet. Adoption rates have differed among different types of
      providers. We studied three predominant types of PHPs to determine why the rate
      of adoption of the standards varies among them. METHODS: This study used a mixed
      methods approach, which allowed the integration of both quantitative and
      qualitative data, to develop an explanatory case study. The case study covered
      three types of private PHPs: pharmacies, dental practices and specialist
      practices. Primary data were collected through face-to-face semi-structured in
      depth interviews and a self-administered postal survey of private health care
      providers. Our study's theoretical framework was based on the diffusion of
      innovation theory. RESULTS: The rate of adoption of mandatory standards varied
      among different types of PHP mainly due to four factors: (1) level of concern
      about negative financial consequences, such as the risk of fines or of losing
      contracts with the Health Insurance Fund of the Republic of Srpska; (2)
      availability of information on the standards and implementation process; (3)
      level of the relevant professional association's support for the introduction of
      standards; and (4) provider's perceptions of the relevant health chamber's
      attitude toward the standards. Opinions conveyed to PHPs by peers slightly
      negatively influenced adoption of the standards at the attitude-forming stage.
      Perceived gains in professional status did not have a major influence on the
      decision to adopt standards. All three types of PHPs perceived the same
      disadvantages of the introduction of safety and quality standards: associated
      expense, increased administrative burden and disruption of service provision.
      CONCLUSIONS: When introducing mandatory quality and safety standards for PHPs,
      national health authorities need to: ensure adequate availability of information
      on the relative advantages of adhering to standards; support the introduction of
      standards with relevant incentives and penalties; and work in partnership with
      relevant professional associations and health chambers to get their buy-in for
      regulation of quality and safety of health services.

PMID- 30286741
TI  - Drug-resistant Enterobacteriaceae colonization is associated with healthcare
      utilization and antimicrobial use among inpatients in Pune, India.
AB  - BACKGROUND: Healthcare exposure may increase drug-resistant Enterobacteriaceae
      colonization risk. Nascent antimicrobial stewardship efforts in low- and middle
      income countries require setting-specific data. We aimed to evaluate risk factors
      for inpatient drug resistant Enterobacteriaceae colonization in a resource
      limited setting in India. METHODS: Patients age >= 6 months admitted with >=24 h
      of fever to a tertiary hospital in Pune, India were enrolled in a prospective
      cohort. Perirectal swabs, collected on admission and hospitalization day 3 or 4,
      were cultured in vancomycin- and ceftriaxone-impregnated media to assess for
      ceftriaxone-resistant Enterobacteriaceae (CTRE) and carbapenem-resistant
      Enterobacteriaceae (CPRE). Multivariable analyses assessed risk factors for drug
      resistant Enterobacteriaceae colonization among participants without admission
      colonization. RESULTS: Admission perirectal swabs were collected on 897
      participants; 87 (10%) had CTRE and 14 (1.6%) had CPRE colonization. Admission
      CTRE colonization was associated with recent healthcare contact (p < 0.01).
      Follow-up samples were collected from 620 participants, 67 (11%) had CTRE and 21
      (3.4%) had CPRE colonization. Among 561 participants without enrollment CTRE
      colonization, 49 (9%) participants were colonized with CTRE at follow-up.
      Detection of CTRE colonization among participants not colonized with CTRE at
      admission was independently associated with empiric third generation
      cephalosporin treatment (adjusted odds ratio [OR] 2.9, 95% CI 1.5-5.8). Follow-up
      transition to CPRE colonization detection was associated with ICU admission (OR
      3.0, 95% CI 1.0-8.5). CONCLUSIONS: Patients who receive empiric third generation
      cephalosporins and are admitted to the ICU rapidly develop detectable CTRE and
      CPRE colonization. Improved antimicrobial stewardship and infection control
      measures are urgently needed upon hospital admission.

PMID- 30286743
TI  - Identifying the prevalence and predictors of suicidal behaviours for indigenous
      males in custody.
AB  - BACKGROUND: High rates of suicidal behaviours among Indigenous Australians have
      been documented. Justice-involved individuals are also at a higher risk for
      engaging in suicidal behaviours. This study sought to ascertain the prevalence
      and correlates of suicidal behaviours for 107 Indigenous adult males in custody
      in Victoria, Australia. METHODS: Participants undertook a structured interview
      comprising a psychiatric assessment. Information on suicidal behaviours (ideation
      and attempts), socio-demographics, environmental stressors, negative life events
      and mental health was obtained. RESULTS: A high proportion of Indigenous males in
      custody experienced lifetime suicidal ideation (63.7%) and over one-half had
      attempted suicide (54.5%). A smaller, yet significant number of participants
      experienced ideation over the past 12 months (27.9%). Having a loved one pass
      away within the past 12 months predicted recent ideation; lifetime ideation and a
      diagnosis of Post-Traumatic Stress Disorder predicted a lifetime suicide attempt.
      CONCLUSIONS: The prevalence of suicidal behaviours among Indigenous people in
      custody is remarkably high. Correlates of suicidal behaviours for Indigenous
      people in custody in this study likely manifest in the community, denoting an
      urgent public health response. Prevention must begin in communities at-risk for
      suicidal behaviours. The development of low intensity mental health service
      infrastructure in communities to promote awareness and provide accessible, least
      restrictive support and treatment is necessary. Correctional institutions must
      also continue to improve custodial suicide prevention and management initiatives.

PMID- 30286744
TI  - Relation between health literacy, self-care and adherence to treatment with oral
      anticoagulants in adults: a narrative systematic review.
AB  - BACKGROUND: Oral anticoagulants (OAC) are widely used in patients with
      cardiovascular diseases. However, for optimal OAC self-care patients must have
      skills, among which health literacy (HL) is highlighted. We aimed to describe the
      relation between HL and self-care in cardiovascular patients on OAC treatment.
      METHODS: Electronic searches were carried out in the PubMed, Scopus, Embase,
      CINAHL, Web of Science, Cochrane Library, SciELO, IME-Biomedicina, CUIDEN Plus
      and LILACS databases, limited to Spanish and English language and between January
      2000-December 2016. Papers reported on adults older than 18 years, taking OAC by
      themselves for at least three months. PRISMA guidelines were used for paper
      selection. RESULTS: We identified 142 articles and finally included 10; almost
      all of them about warfarin. Our results suggest that in patients taking OAC
      treatments there is a positive relationship between HL and the level of
      knowledge. In addition, a small percentage of participants on the selected papers
      recognized the side effects and complications associated with OAC treatment.
      Lower HL level was associated with greater knowledge deficits and less adherence
      to treatment. CONCLUSION: There is a paucity of research evaluating the effect of
      HL on diverse aspects of OAC treatments. There is a need to expand the evidence
      base regarding appropriate HL screening tools, determinants of adequate knowledge
      and optimal behaviours related to OAC self-management.

PMID- 30286745
TI  - Successfully treating 90 patients with obsessive compulsive disorder in eight
      days: the Bergen 4-day treatment.
AB  - BACKGROUND: Oslo University Hospital, Norway, had by autumn 2016, accumulated a
      waiting list of 101 patients with obsessive-compulsive disorder (OCD) who had a
      legal right to receive treatment by a specialized OCD team. In this challenging
      situation, the Bergen OCD-team suggested to solve the problem by offering all
      patients an option for the rapid Bergen 4-day treatment (B4DT). The B4DT is an
      individual treatment delivered during four consecutive days in a group of six
      patients with the same number of therapists. The approach has previously shown a
      post-treatment response rate of 90% and a 3-month remission rate of 70%. METHODS:
      Ninety-seven of the wait-list patients were available for the scheduled time
      slots, and 90 received the 4-day format during 8 days (45 patients each week).
      The therapists were recruited from 22 different specialized OCD-teams from all
      over Norway, and 44 (68%) had not previously delivered the 4-day format. RESULTS:
      Post-treatment; 91.1% of the patients were classified as responders, and 72.2%
      were in remission. At 3-month follow-up; 84.4 were classified as responders and
      the remission rate was 67.7%. Oslo University Hospital now offers the 4-day
      treatment as standard treatment for OCD. CONCLUSIONS: We conclude that the B4DT
      is an acceptable and potentially effective OCD-treatment.

PMID- 30286747
TI  - The hsa-miR-181a-5p reduces oxidation resistance by controlling SECISBP2 in
      osteoarthritis.
AB  - BACKGROUND: The phenotypes of osteoarthritis (OA) consist of cartilage
      extracellular matrix (ECM) metabolism disorder and the breakdown of cartilage
      homeostasis, which are induced by pro-inflammatory factors and oxidative stress.
      Selenoproteins regulated by selenocysteine insertion sequence binding protein 2
      (SBP2) are highly effective antioxidants, but their regulatory mechanisms,
      particularly the involvement of miRNAs, are not fully understood. METHODS: To
      explore whether miR-181a-5p and SBP2 are involved in OA pathogenesis, we
      established an IL-1beta model using the chondrocyte SW1353 cell line. Next, we up
      or down-regulated SBP2 and miRNA-181a-5p expression in the cells. Finally, we
      measured the expression of miRNA-181a-5p, SBP2 and three selenoproteins in OA
      cartilage and peripheral blood. RESULTS: The results showed that IL-1beta
      increased hsa-miR-181a-5p and decreased SBP2 in a time- and dose-dependent
      manner. GPX1 and GPX4, which encode crucial glutathione peroxidase antioxidant
      enzymes, were up-regulated along with SBP2 and miR-181a-5p. Furthermore, SBP2
      showed a significant negative correlation with miR-181a-5p during induced ATDC5
      cell differentiation. There was lower GPX1 and GPX4 mRNA expression and SBP2
      protein expression in damaged cartilage than in smooth cartilage from the same OA
      sample, and hsa-miR-181a-5p expression on the contrary. Similar results were
      observed in peripheral blood. In conclusion, we have reported a novel pathway in
      which pro-inflammatory factors, miRNA, SBP2 and selenoproteins are associated
      with oxidation resistance in cartilage. CONCLUSION: Overall, this study provides
      the first comprehensive evidence that pro-inflammatory factors cause changes in
      the cartilage antioxidant network and describes the discovery of novel mediators
      of cartilage oxidative stress and OA pathophysiology. Our data suggest that miR
      181a-5p may be used to develop novel early-stage diagnostic and therapeutic
      strategies for OA.

PMID- 30286746
TI  - "How am I going to live?": exploring barriers to ART adherence among adolescents
      and young adults living with HIV in Uganda.
AB  - BACKGROUND: Studies from sub-Saharan Africa (SSA) document how barriers to ART
      adherence present additional complications among adolescents and young adults
      living with HIV. We qualitatively explored barriers to ART adherence in Uganda
      among individuals age 14-24 to understand the unique challenges faced by this age
      group. METHODS: We conducted focus group (FG) discussions with Community Advisory
      Board members (n = 1), health care providers (n = 2), and male and female groups
      of adolescents age 14-17 (n = 2) and youth age 18-24 (n = 2) in Kampala, Uganda.
      FGs were transcribed verbatim and translated from Luganda into English. Two
      investigators independently reviewed all transcripts, developed a detailed
      codebook, achieved a pooled Cohen's Kappa of 0.79 and 0.80, and used a directed
      content analysis to identify key themes. RESULTS: Four barriers to ART adherence
      emerged: 1) poverty limited adolescents' ability to buy food and undercut efforts
      to become economically independent in their transition from adolescence to
      adulthood; 2) school attendance limited their privacy, further disrupting ART
      adherence; 3) family support was unreliable, and youth often struggled with a
      constant change in guardianship because they had lost their biological parents to
      HIV. In contrast peer influence, especially among HIV-positive youth, was strong
      and created an important network to support ART adherence; 4) the burden of
      taking multiple medications daily frustrated youth, often leading to so-called
      'drug holidays.' Adolescent and youth-specific issues around disclosure emerged
      across three of the four barriers. CONCLUSIONS: To be effective, programs and
      policies to improve ART adherence among youth in Uganda must address the special
      challenges that adolescents and young adults confront in achieving optimal
      adherence. For example, training on budgeting and savings practices could help
      promote their transition to financial independence. School staff could develop
      strategies to help students take their medications consistently and
      confidentially. While challenging to extend the range of services provided by HIV
      clinics, successful efforts will require engaging the family, peers, and larger
      community of health and educational providers to support adolescents and young
      adults living with HIV to live longer and healthier lives. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT02514356 . Registered August 3, 2015.

PMID- 30286748
TI  - Balancing feasibility and comprehensiveness: examining medications for reducing
      emergency hospital admissions.
AB  - Emergency hospital admissions are common, with several interventions having been
      developed to reduce their rates. Bobrovitz et al. summarized the available body
      of evidence regarding pharmacologic therapies aimed at reducing emergency
      hospital admissions, and identified 28 medications for which high- or moderate
      quality evidence supports their use, 11 of which were identified as being
      supported by current guideline recommendations. Additionally, the authors
      identified 28 medications supported by low- or very low-quality evidence, which
      can serve as targets for future research. The article by Bobrovitz et al.
      presents a good summary of the evidence, albeit with limitations in the search
      strategy that cannot guarantee the review as comprehensive. Despite this, the
      review has important implications for policymakers, guideline panels,
      researchers, clinicians, and funders since the identified medications can either
      be targets for quality improvement initiatives or for future research. Bobrovitz
      et al.'s review highlights the challenge that systematic reviewers face when
      balancing feasibility and comprehensiveness.Please see related article:
      https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1104-9.

PMID- 30286749
TI  - Two decades of antenatal and delivery care in Uganda: a cross-sectional study
      using Demographic and Health Surveys.
AB  - BACKGROUND: Uganda halved its maternal mortality to 343/100,000 live births
      between 1990 and 2015, but did not meet the Millennium Development Goal 5.
      Skilled, timely and good quality antenatal (ANC) and delivery care can prevent
      the majority of maternal/newborn deaths and stillbirths. We examine coverage,
      equity, sector of provision and content of ANC and delivery care between 1991 and
      2011. METHODS: We conducted a repeated cross-sectional study using four Uganda
      Demographic and Health Surveys (1995, 2000, 2006 and 2011).Using the most recent
      live birth and adjusting for survey sampling, we estimated percentage and
      absolute number of births with ANC (any and 4+ visits), facility delivery,
      caesarean sections and complete maternal care. We assessed socio-economic
      differentials in these indicators by wealth, education, urban/rural residence,
      and geographic zone on the 1995 and 2011 surveys. We estimated the proportions of
      ANC and delivery care provided by the public and private (for-profit and not-for
      profit) sectors, and compared content of ANC and delivery care between sectors.
      Statistical significance of differences were evaluated using chi-square tests.
      RESULTS: Coverage with any ANC remained high over the study period (> 90% since
      2001) but was of insufficient frequency; < 50% of women who received any ANC
      reported 4+ visits. Facility-based delivery care increased slowly, reaching 58%
      in 2011. While significant inequalities in coverage by wealth, education,
      residence and geographic zone remained, coverage improved for all indicators
      among the lowest socio-economic groups of women over time. The private sector
      market share declined over time to 14% of ANC and 25% of delivery care in 2011.
      Only 10% of women with 4+ ANC visits and 13% of women delivering in facilities
      received all measured care components. CONCLUSIONS: The Ugandan health system had
      to cope with more than 30,000 additional births annually between 1991 and 2011.
      The majority of women in Uganda accessed ANC, but this contact did not result in
      care of sufficient frequency, content, and continuum of care (facility delivery).
      Providers in both sectors require quality improvements. Achieving universal
      health coverage and maternal/newborn SDGs in Uganda requires prioritising poor,
      less educated and rural women despite competing priorities for financial and
      human resources.

PMID- 30286750
TI  - A simulation tool for better management of retinal services.
AB  - BACKGROUND: Advances in the management of retinal diseases have been fast-paced
      as new treatments become available, resulting in increasing numbers of patients
      receiving treatment in hospital retinal services. These patients require frequent
      and long-term follow-up and repeated treatments, resulting in increased pressure
      on clinical workloads. Due to limited clinic capacity, many National Health
      Service (NHS) clinics are failing to maintain recommended follow-up intervals for
      patients receiving care. As such, clear and robust, long term retinal service
      models are required to assess and respond to the needs of local populations, both
      currently and in the future. METHODS: A discrete event simulation (DES) tool was
      developed to facilitate the improvement of retinal services by identifying
      efficiencies and cost savings within the pathway of care. For a mid-size hospital
      in England serving a population of over 500,000, we used 36 months of patient
      level data in conjunction with statistical forecasting and simulation to predict
      the impact of making changes within the service. RESULTS: A simulation of
      increased demand and a potential solution of the 'Treat and Extend' (T&E) regimen
      which is reported to result in better outcomes, in combination with virtual
      clinics which improve quality, effectiveness and productivity and thus increase
      capacity is presented. Without the virtual clinic, where T&E is implemented along
      with the current service, we notice a sharp increase in the number of follow-ups,
      number of Anti-VEGF injections, and utilisation of resources. In the case of
      combining T&E with virtual clinics, there is a negligible (almost 0%) impact on
      utilisation of resources. CONCLUSIONS: Expansion of services to accommodate
      increasing number of patients seen and treated in retinal services is feasible
      with service re-organisation. It is inevitable that some form of initial
      investment is required to implement service expansion through T&E and virtual
      clinics. However, modelling with DES indicates that such investment is outweighed
      by cost reductions in the long term as more patients receive optimal treatment
      and retain vision with better outcomes. The model also shows that the service
      will experience an average of 10% increase in surplus capacity.

PMID- 30286751
TI  - Contracting-out urban primary health care in Bangladesh: a qualitative
      exploration of implementation processes and experience.
AB  - BACKGROUND: Contracting-out (CO) to non-state providers is used widely to
      increase access to health care, but it entails many implementation challenges.
      Using Bangladesh's two decades of experience with contracting out Urban Primary
      Health Care (UPHC), this paper identifies contextual, contractual, and actor
      related factors that require consideration when implementing CO in Low- and
      Middle- Income Countries. METHODS: This qualitative case-study is based on 42 in
      depth interviews with past and present stakeholders working with the government
      and the UPHC project, as well as a desk review of key project documents. The
      Health Policy Triangle framework is utilized to differentiate among multiple
      intersecting contextual, contractual and actor-related factors that characterize
      and influence complex implementation processes. RESULTS: In Bangladesh, the
      contextual factors, both intrinsic and extrinsic to the health system, deeply
      impacted the CO process. These included competition with other health projects,
      public sector reforms, and the broader national level political and bureaucratic
      environment. Providing free services to the poor and a target to recover cost
      were two contradictory conditions set out in the contract and were difficult for
      providers to achieve. In relation to actors, the choice of the executing body led
      to complications, functionally disempowering local government institutions
      (cities and municipalities) from managing CO processes, and discouraging
      integration of CO arrangements into the broader national health system. Politics
      and power dynamics undermined the ethical selection of project areas. Ultimately,
      these and other factors weakened the project's ability to achieve one of its
      original objectives: to decentralize management responsibilities and develop
      municipal capacity in managing contracts. CONCLUSIONS: This study calls attention
      to factors that need to be addressed to successfully implement CO projects, both
      in Bangladesh and similar countries. Country ownership is crucial for adapting
      and integrating CO in national health systems. Concurrent processes must be
      ensured to develop local CO capacity. CO modalities must be adaptable and
      responsive to changing context, while operating within an agreed-upon and
      appropriate legal framework with a strong ethical foundation.

PMID- 30286752
TI  - On the epidemiology of Plasmodium vivax malaria: past and present with special
      reference to the former USSR.
AB  - Presently, many malaria-endemic countries in the world are transitioning towards
      malaria elimination. Out of the 105 countries with ongoing malaria transmission,
      10 countries are classified as being in the pre-elimination phase of malaria
      control, and 9 countries are in the malaria elimination stage, whereas 7
      countries are classified as being in the prevention of introduction phase.
      Between 2000 and 2015, 17 countries eliminated malaria (i.e., attained zero
      indigenous cases for 3 years or more). Seven countries were certified by the WHO
      as having successfully eliminated malaria. The purpose of this review was to
      analyse the epidemiological characteristics of vivax malaria during the various
      stages of malaria eradication (elimination) programmes in different countries in
      the past and present. Experiences of the republics of the former USSR with
      malaria are interesting, particularly since the data overwhelmingly were
      published in Russian and might not be known to western readers. Among the most
      important characteristics of Plasmodium vivax epidemiology at present are changes
      in the ratio of the short-incubation P. vivax to long-incubation P. vivax, the
      incidence of severe P. vivax cases, the increased numbers of asymptomatic P.
      vivax cases, the reduced response to anti-malarials and a few others. Various
      factors contributing towards the peculiarities of P. vivax epidemiology are
      discussed.

PMID- 30286753
TI  - The head shaft angle is associated with hip displacement in children at GMFCS
      levels III-V - a population based study.
AB  - BACKGROUND: An increased Head Shaft Angle (HSA) has been reported as a risk
      factor for hip displacement in children with cerebral palsy (CP) but opinions
      differ in the literature. The purpose of this study was to re-evaluate the
      relationship between HSA and hip displacement in a different population of
      children with CP. METHODS: The Cerebral Palsy Integrated Pathway Scotland
      surveillance programme includes 95% of all children with CP in Scotland. The
      pelvic radiographs from 640 children in GMFCS levels III-V were chosen. The most
      displaced hip was analysed and the radiographs used were those taken at the
      child's first registration in the database to avoid the potential effects of
      surveillance on subsequent hip centration. A logistic regression model was used
      with hip displacement (migration percentage [MP] >=40%) as outcome and HSA,
      GMFCS, age and sex as covariates. RESULTS: The MP was >=40% in 118 hips with a
      mean HSA of 164 degrees  (range 121-180 degrees ) and < 40% in 522 hips with a
      mean HSA of 160 degrees  (range 111-180 degrees ). The logistic regression
      analysis showed no significant influence of age and sex on MP in this population
      but a high GMFCS level was strongly associated with hip displacement. An
      increased HSA was also associated with hip displacement, a 10 degrees  difference
      in HSA for children adjusted for age, sex, and GMFCS gave an odds ratio of 1.26
      for hip displacement equal or above 40% (p = 0.009) and hips with HSA above 164.5
      degrees had an odds ratio of 1.96 compared with hips with HSA below 164.5 degrees
      (p = 0.002). CONCLUSION: These findings confirm that HSA is associated with hip
      displacement in children in GMFCS levels III-V.

PMID- 30286754
TI  - Computational analysis of the interactions of a novel cephalosporin derivative
      with beta-lactamases.
AB  - BACKGROUND: One of the main concerns of the modern medicine is the frightening
      spread of antimicrobial resistance caused mainly by the misuse of antibiotics.
      The researchers worldwide are actively involved in the search for new classes of
      antibiotics, and for the modification of known molecules in order to face this
      threatening problem. We have applied a computational approach to predict the
      interactions between a new cephalosporin derivative containing an additional beta
      lactam ring with different substituents, and several serine beta-lactamases
      representative of the different classes of this family of enzymes. RESULTS: The
      results of the simulations, performed by using a covalent docking approach, has
      shown that this compound, although able to bind the selected beta-lactamases, has
      a different predicted binding score for the two beta-lactam rings, suggesting
      that one of them could be more resistant to the attack of these enzymes and stay
      available to perform its bactericidal activity. CONCLUSIONS: The detailed
      analysis of the complexes obtained by these simulations suggests possible hints
      to modulate the affinity of this compound towards these enzymes, in order to
      develop new derivatives with improved features to escape to degradation.

PMID- 30286755
TI  - Supporting maintenance of sugar-sweetened beverage reduction using automated
      versus live telephone support: findings from a randomized control trial.
AB  - BACKGROUND: Although reducing sugar-sweetened beverage (SSB) intake is an
      important behavioral strategy to improve health, no known SSB-focused behavioral
      trial has examined maintenance of SSB behaviors after an initial reduction.
      Guided by the RE-AIM framework, this study examines 6-18 month and 0-18 month
      individual-level maintenance outcomes from an SSB reduction trial conducted in a
      medically-underserved, rural Appalachia region of Virginia. Reach and
      implementation indicators are also reported. METHODS: Following completion of a 6
      month, multi-component, behavioral RCT to reduce SSB intake (SIPsmartER condition
      vs. comparison condition), participants were further randomized to one of three
      12-month maintenance conditions. Each condition included monthly telephone calls,
      but varied in mode and content: 1) interactive voice response (IVR) behavior
      support, 2) human-delivered behavior support, or 3) IVR control condition.
      Assessments included the Beverage Intake Questionnaire (BEVQ-15), weight, BMI,
      and quality of life. Call completion rates and costs were tracked. Analysis
      included descriptive statistics and multilevel mixed-effects linear regression
      models using intent-to-treat procedures. RESULTS: Of 301 subjects enrolled in the
      6-month RCT, 242 (80%) were randomized into the maintenance phase and 235 (78%)
      included in the analyses. SIPsmartER participants maintained significant 0-18
      month decreases in SSB. For SSB, weight, BMI and quality of life, there were no
      significant 6-18 month changes among SIPsmartER participants, indicating post
      program maintenance. The IVR-behavior participants reported greater reductions in
      SSB kcals/day during the 6-18 month maintenance phase, compared to the IVR
      control participants (- 98 SSB kcals/day, 95% CI = - 196, - 0.55, p < 0.05); yet
      the human-delivered behavior condition was not significantly different from
      either the IVR-behavior condition (27 SSB kcals/day, 95% CI = - 69, 125) or IVR
      control condition (- 70 SSB kcals/day, 95% CI = - 209, 64). Call completion rates
      were similar across maintenance conditions (4.2-4.6 out of 11 calls); however,
      loss to follow-up was greatest in the IVR control condition. Approximated costs
      of IVR and human-delivered calls were remarkably similar (i.e.,
      $3.15/participant/month or $38/participant total for the 12-month maintenance
      phase), yet implications for scalability and sustainability differ. CONCLUSION:
      Overall, SIPsmartER participants maintained improvements in SSB behaviors. Using
      IVR to support SSB behaviors is effective and may offer advantages as a scalable
      maintenance strategy for real-world systems in rural regions to address excessive
      SSB consumption. TRIAL REGISTRY: Clinicaltrials.gov; NCT02193009 ; Registered 11
      July 2014. Retrospectively registered.

PMID- 30286757
TI  - Government resource contributions to the private-not-for-profit sector in Uganda:
      evolution, adaptations and implications for universal health coverage.
AB  - BACKGROUND: A case study was prepared examining government resource contributions
      (GRCs) to private-not-for-profit (PNFP) providers in Uganda. It focuses on
      Primary Health Care (PHC) grants to the largest non-profit provider network, the
      Uganda Catholic Medical Bureau (UCMB), from 1997 to 2015. The framework of
      complex adaptive systems was used to explain changes in resource contributions
      and the relationship between the Government and UCMB. METHODS: Documents and key
      informant interviews with the important actors provided the main sources of
      qualitative data. Trends for GRCs and service outputs for the study period were
      constructed from existing databases used to monitor service inputs and outputs.
      The case study's findings were validated during two meetings with a broad set of
      stakeholders. RESULTS: Three major phases were identified in the evolution of
      GRCs and the relationship between the Government and UCMB: 1) Initiation, 2)
      Rapid increase in GRCs, and 3) Declining GRCs. The main factors affecting the
      relationship's evolution were: 1) Financial deficits at PNFP facilities, 2)
      advocacy by PNFP network leaders, 3) changes in the government financial resource
      envelope, 4) variations in the "good will" of government actors, and 5) changes
      in donor funding modalities. Responses to the above dynamics included changes in
      user fees, operational costs of PNFPs, and government expectations of UCMB.
      Quantitative findings showed a progressive increase in service outputs despite
      the declining value of GRCs during the study period. CONCLUSIONS: GRCs in Uganda
      have evolved influenced by various factors and the complex interactions between
      government and PNFPs. The Universal Health Coverage (UHC) agenda should pay
      attention to these factors and their interactions when shaping how governments
      work with PNFPs to advance UHC. GRCs could be leveraged to mitigate the financial
      burden on communities served by PNFPs. Governments seeking to advance UHC goals
      should explore policies to expand GRCs and other modalities to subsidize the
      operational costs of PNFPs.

PMID- 30286756
TI  - Screening and identification of potential novel biomarker for diagnosis of
      complicated Plasmodium vivax malaria.
AB  - BACKGROUND: In the recent years Plasmodium vivax has been reported to cause
      severe infections associated with mortality. Clinical evaluation has limited
      accuracy for the early identification of the patients progressing towards the
      fatal condition. Researchers have tried to identify the serum and the plasma
      based indicators of the severe malaria. Discovery of MicroRNA (miRNA) has opened
      up an era of identification of early biomarkers for various infectious and non
      infectious diseases. MicroRNAs (miRNA) are the small non-coding RNA molecules of
      length 19-24 nts and are responsible for the regulation of the majority of human
      gene expressions at post transcriptional level. METHODS: We identified the
      differentially expressed miRNAs by microarray and validated the selected miRNAs
      by qRT-PCR. We assessed the diagnostic potential of these up-regulated miRNAs for
      complicated P. vivax malaria. Futher, the bioinformtic analysis was performed to
      construct protein-protein and mRNA-miRNA networks to identify highly regulated
      miRNA. RESULTS: In the present study, utility of miRNA as potential biomarker of
      complicated P. vivax malaria was explored. A total of 276 miRNAs were found to be
      differentially expressed by miRNA microarray and out of which 5 miRNAs (hsa-miR
      7977, hsa-miR-28-3p, hsa-miR-378-5p, hsa-miR-194-5p and hsa-miR-3667-5p) were
      found to be significantly up-regulated in complicated P. vivax malaria patients
      using qRT-PCR. The diagnostic potential of these 5 miRNAs were found to be
      significant with sensitivity and specificity of 60-71% and 69-81% respectively
      and area under curve (AUC) of 0.7 (p < 0.05). Moreover, in silico analysis of the
      common targets of up-regulated miRNAs revealed UBA52 and hsa-miR-7977 as majorly
      regulated hubs in the PPI and mRNA-miRNA networks, suggesting their putative role
      in complicated P. vivax malaria. CONCLUSION: miR-7977 might act as a potential
      biomarker for differentiating complicated P. vivax malaria from uncomplicated
      type. The elevated levels of miR-7977 may have a role to play in the disease
      pathology through UBA52 or TGF-beta signalling pathway.

PMID- 30286758
TI  - Towards universal health coverage: a mixed-method study mapping the development
      of the faith-based non-profit sector in the Ghanaian health system.
AB  - BACKGROUND: Faith-based non-profit (FBNP) providers have had a long-standing role
      as non-state, non-profit providers in the Ghanaian health system. They have
      historically been considered to be important in addressing the inequitable
      geographical distribution of health services and towards the achievement of
      universal health coverage (UHC), but in changing contexts, this contribution is
      being questioned. However, any assessment of contribution is hampered by the lack
      of basic information about their comparative presence and coverage in the
      Ghanaian health system. In response, since the 1950s, there have been repeated
      calls for the 'mapping' of faith-based health assets. METHODS: A historically
      focused mixed-methods study was conducted, collecting qualitative and
      quantitative data and combining geospatial mapping with varied documentary
      resources (secondary and primary, current and archival). Geospatial maps were
      developed, providing a visual representation of changes in the spatial footprint
      of the Ghanaian FBNP health sector. RESULTS: The geospatial maps show that FBNPs
      were originally located in rural remote areas of the country but that this
      service footprint has evolved over time, in line with changing social, political
      and economic contexts. CONCLUSION: FBNPs have had a long-standing role in the
      provision of health services and remain a valuable asset within national health
      systems in Ghana and sub-Saharan Africa more broadly. Collaboration between the
      public sector and such non-state providers, drawing on the comparative strengths
      and resources of FBNPs and focusing on whole system strengthening, is essential
      for the achievement of UHC.

PMID- 30286759
TI  - Molecular network-based identification of competing endogenous RNAs and mRNA
      signatures that predict survival in prostate cancer.
AB  - BACKGROUND: The aim of the study is described the regulatory mechanisms and
      prognostic values of differentially expressed RNAs in prostate cancer and
      construct an mRNA signature that predicts survival. METHODS: The RNA profiles of
      499 prostate cancer tissues and 52 non-prostate cancer tissues from TCGA were
      analyzed. The differential expression of RNAs was examined using the edgeR
      package. Survival was analyzed by Kaplan-Meier method. microRNA (miRNA),
      messenger RNA (mRNA), and long non-coding RNA (lncRNA) networks from the miRcode
      database were constructed, based on the differentially expressed RNAs between non
      prostate and prostate cancer tissues. RESULTS: A total of 773 lncRNAs, 1417
      mRNAs, and 58 miRNAs were differentially expressed between non-prostate and
      prostate cancer samples. The newly constructed ceRNA network comprised 63
      prostate cancer-specific lncRNAs, 13 miRNAs, and 18 mRNAs. Three of 63
      differentially expressed lncRNAs and 1 of 18 differentially expressed mRNAs were
      significantly associated with overall survival in prostate cancer (P value <
      0.05). After the univariate and multivariate Cox regression analyses, 4 mRNAs
      (HOXB5, GPC2, PGA5, and AMBN) were screened and used to establish a predictive
      model for the overall survival of patients. Our ROC curve analysis revealed that
      the 4-mRNA signature performed well. CONCLUSION: These ceRNAs may play a critical
      role in the progression and metastasis of prostate cancer and are thus candidate
      therapeutic targets and potential prognostic biomarkers. A novel model that
      incorporated these candidates was established and might provide more powerful
      prognostic information in predicting survival in prostate cancer.

PMID- 30286761
TI  - Perceptions of patients with chronic obstructive pulmonary disease and their
      health care providers towards using mHealth for self-management of exacerbations:
      a qualitative study.
AB  - BACKGROUND: Self-management of exacerbations in COPD patients is important to
      reduce exacerbation impact. There is a need for more comprehensive and
      individualized interventions to improve exacerbation-related self-management
      behavior. The use of mobile health (mHealth) could help to achieve a wide variety
      of behavioral goals. Understanding of patients and health care providers
      perspectives towards using mHealth in promoting self-management will greatly
      enhance the development of solutions with optimal usability and feasibility.
      Therefore, the aim of this study was to explore perceptions of COPD patients and
      their health care providers towards using mHealth for self-management of
      exacerbations. METHODS: A qualitative study using focus group interviews with
      COPD patients (n = 13) and health care providers (HCPs) (n = 6) was performed to
      explore perceptions towards using mHealth to support exacerbation-related self
      management. Data were analyzed by a thematic analysis. RESULTS: COPD patients and
      HCPs perceived mostly similar benefits and barriers of using mHealth for
      exacerbation-related self-management. These perceived benefits and barriers seem
      to be important drivers in the willingness to use mHealth. Both patients and HCPs
      strengthen the need for a multi-component and tailored mHealth intervention that
      improves patients' exacerbation-related self-management by determining their
      health status and providing adequate information, decision support and feedback
      on self-management behavior. Most importantly, patients and HCPs considered an
      mHealth intervention as support to improve self-management and emphasized that it
      should never replace patients' own feelings nor undermine their own decisions. In
      addition, the intervention should be complementary to regular contact with HCPs,
      as personal contact with a HCP was considered to be very important. To optimize
      engagement with mHealth, patients should have a positive attitude toward using
      mHealth and an mHealth intervention should be attractive, rewarding and safe.
      CONCLUSIONS: This study provided insight into perceptions of COPD patients and
      their HCPs towards using mHealth for self-management of exacerbations. This study
      points out that future mHealth interventions should focus on developing self
      management skills over time by providing adequate information, decision support
      and feedback on self-management behavior and that mHealth should complement
      regular care. To optimize engagement, mHealth interventions should be attractive,
      rewarding, safe and tailored to the patient needs.

PMID- 30286760
TI  - Effects of a single dose of beetroot juice on cycling time trial performance at
      ventilatory thresholds intensity in male triathletes.
AB  - BACKGROUND: Beetroot juice (BJ) is classified as a high-level supplement for
      improving sports performance. There is some controversy over the benefits of BJ
      supplementation for endurance exercise performance, especially when referring to
      well-trained athletes. This study examines the effects of acute BJ
      supplementation on cardioventilatory responses, exercise economy/efficiency, slow
      component of oxygen uptake, time trial performance, blood lactate, energy
      consumption, and carbohydrate and fat oxidation. METHODS: Twelve well-trained,
      male triathletes (aged 21-47 yr) were assigned in a randomized, double-blind,
      crossover design to receive 70 ml of BJ (6.5 mmol NO3-) or placebo (PL). Three
      hours after taking the supplement, participants completed an endurance test on a
      cycle ergometer at a constant work rate (W) corresponding to first ventilatory
      threshold (VT1) (30 min) and second ventilatory threshold (VT2) time trial (~ 15
      min). RESULTS: Maximal oxygen uptake was 54.78 +/- 3.13 mL.min- 1.kg- 1, and
      gross efficiency was > 22% at each load intensity and experimental condition. No
      significant interaction effect (supplement*intensity) was observed on any of the
      cardioventilatory variables, efficiency/economy, VT2 time trial, energy
      expenditure, carbohydrate oxidation and fat oxidation (p > 0.05). CONCLUSION: Our
      findings do not support an improvement in the variables examined in response to
      acute BJ supplementation. Probably, higher doses are needed for improving time
      trial performance in male triathletes during a cycle ergometer test conducted at
      a load intensity equivalent to the first and second ventilatory threshold.

PMID- 30286762
TI  - Prognostic significance of metastatic lymph node ratio: the lymph node ratio
      could be a prognostic indicator for patients with gastric cancer.
AB  - BACKGROUND: To demonstrate the prognostic significance and value of lymph node
      ratio (LNR) and evaluate the possibility of becoming a new indicator to enhance
      the current Union for International Cancer Control (UICC)/American Joint
      Committee on Cancer (AJCC) tumor, lymph node, metastasis (TNM) staging system.
      METHODS: Our retrospective study included 221 patients who got gastric cancer and
      underwent curative gastrectomy between 2005 and 2012 at the Fourth Hospital
      Affiliated of China Medical University. The log-rank test was used to compare the
      clinicopathological variables. The Kaplan-Meier method and Cox proportional
      hazard regression model was used to perform the univariate analysis and
      multivariate statistical survival analysis. RESULTS: The patients with a better
      differentiated pathological type; an earlier stage of T staging, N staging, and
      TNM staging; and a lesser LNR would have a longer survival time according to the
      univariate analysis. As for the multivariate analysis, the Grade, T stage, N
      stage, and LNR had the statistical significance. Both in group 1 (the number of
      lymph nodes examined >= 15, namely LN >= 15) and group 2 (LN < 15), the LNR had
      statistical significance and the median survival time would decrease with the
      increase of the LNR. It was still statistically significant between group LNR1
      and group LNR2 which were regrouped by the new cut-off value. CONCLUSION: The LNR
      could estimate the prognosis of patients with curative gastrectomy regardless of
      the number of lymph nodes examined. Thus LNR could become a new indicator to
      enhance the current TNM stage system.

PMID- 30286763
TI  - Realities and experiences of community health volunteers as agents for behaviour
      change: evidence from an informal urban settlement in Kisumu, Kenya.
AB  - BACKGROUND: Community health workers play an important role in health service
      delivery and are increasingly involved in behaviour change interventions,
      including for hygiene-related behaviour change. However, their role and capacity
      to deliver behaviour change interventions, particularly in high-density urban
      settlements, remain under-researched. This study examines the behaviour change
      related activities of community health volunteers (CHVs)-community health workers
      affiliated with the Kenyan Ministry of Health-in a peri-urban settlement in
      Kenya, in order to assess their capabilities, opportunities to work effectively,
      and sources of motivation. METHODS: This mixed-methods study included a census of
      16 CHVs who work in the study area. All CHVs participated in structured
      observations of their daily duties, structured questionnaires, in-depth
      interviews, and two focus group discussions. Structured data were analysed
      descriptively. Thematic content analysis was followed for qualitative data.
      Results were synthesized and interpreted using the capability, opportunity,
      motivation for behaviour change framework, COM-B. RESULTS: In addition to their
      responsibilities with the Ministry of Health, CHVs partnered with a range of non
      governmental organizations engaged in health and development programming, often
      receiving small stipends from these organizations. CHVs reported employing a
      limited number of behaviour change techniques when interacting with community
      members at the household level. Capability: While supervision and support from
      the MOH was robust, CHV training was inconsistent and inadequate with regard to
      behaviour change and CHVs often lacked material resources necessary for their
      work. Opportunity: CHVs spent very little time with the households in their
      allocated catchment area. The number of households contacted per day was
      insufficient to reach all assigned households within a given month as required
      and the brief time spent with households limited the quality of engagement.
      MOTIVATION: Lack of compensation was noted as a demotivating factor for CHVs.
      This was compounded by the challenging social environment and CHVs' low
      motivation to encourage behaviour change in local communities. CONCLUSIONS: In a
      complex urban environment, CHVs faced challenges that limited their capacity to
      be involved in behaviour change interventions. More resources, better
      coordination, and additional training in modern behaviour change approaches are
      needed to ensure their optimal performance in implementing health programmes.

PMID- 30286766
TI  - Moving towards universal health coverage: engaging non-state providers.
AB  - This editorial provides an overview of the special issue "Moving towards UHC:
      engaging non-state providers". It begins by describing the rationale underlying
      the Alliance's choice of a research program addressing issues of non-state
      providers and briefly discusses the research process this entailed. This is
      followed by a summary of the findings and key messages of each of the eight
      articles included in the issue. The editorial concludes with a series of
      reflections regarding lessons learnt about the engagement of non-state providers,
      methodological challenges, areas for future research as well as the contribution
      of the research program towards efforts to build capacity and strengthen health
      systems towards universal health coverage.

PMID- 30286764
TI  - RNA-induced epigenetic silencing inhibits HIV-1 reactivation from latency.
AB  - BACKGROUND: Current antiretroviral therapy is effective in controlling HIV-1
      infection. However, cessation of therapy is associated with rapid return of
      viremia from the viral reservoir. Eradicating the HIV-1 reservoir has proven
      difficult with the limited success of latency reactivation strategies and
      reflects the complexity of HIV-1 latency. Consequently, there is a growing need
      for alternate strategies. Here we explore a "block and lock" approach for
      enforcing latency to render the provirus unable to restart transcription despite
      exposure to reactivation stimuli. Reactivation of transcription from latent HIV-1
      proviruses can be epigenetically blocked using promoter-targeted shRNAs to
      prevent productive infection. We aimed to determine if independent and combined
      expression of shRNAs, PromA and 143, induce a repressive epigenetic profile that
      is sufficiently stable to protect latently infected cells from HIV-1 reactivation
      when treated with a range of latency reversing agents (LRAs). RESULTS: J-Lat 9.2
      cells, a model of HIV-1 latency, expressing shRNAs PromA, 143, PromA/143 or
      controls were treated with LRAs to evaluate protection from HIV-1 reactivation as
      determined by levels of GFP expression. Cells expressing shRNA PromA, 143, or
      both, showed robust resistance to viral reactivation by: TNF, SAHA, SAHA/TNF,
      Bryostatin/TNF, DZNep, and Chaetocin. Given the physiological importance of TNF,
      HIV-1 reactivation was induced by TNF (5 ng/mL) and ChIP assays were performed to
      detect changes in expression of epigenetic markers within chromatin in both
      sorted GFP- and GFP+ cell populations, harboring latent or reactivated
      proviruses, respectively. Ordinary two-way ANOVA analysis used to identify
      interactions between shRNAs and chromatin marks associated with repressive or
      active chromatin in the integrated provirus revealed significant changes in the
      levels of H3K27me3, AGO1 and HDAC1 in the LTR, which correlated with the extent
      of reduced proviral reactivation. The cell line co-expressing shPromA and sh143
      consistently showed the least reactivation and greatest enrichment of chromatin
      compaction indicators. CONCLUSION: The active maintenance of epigenetic silencing
      by shRNAs acting on the HIV-1 LTR impedes HIV-1 reactivation from latency. Our
      "block and lock" approach constitutes a novel way of enforcing HIV-1 "super
      latency" through a closed chromatin architecture that renders the virus resistant
      to a range of latency reversing agents.

PMID- 30286767
TI  - Contracting-out primary health care services in Tanzania towards UHC: how policy
      processes and context influence policy design and implementation.
AB  - BACKGROUND: Governments increasingly recognize the need to engage non-state
      providers (NSPs) in health systems in order to move successfully towards
      Universal Health Coverage (UHC). One common approach to engaging NSPs is to
      contract-out the delivery of primary health care services. Research on
      contracting arrangements has typically focused on their impact on health service
      delivery; less is known about the actual processes underlying the development and
      implementation of interventions and the contextual factors that influence these.
      This paper reports on the design and implementation of service agreements (SAs)
      between local governments and NSPs for the provision of primary health care
      services in Tanzania. It examines the actors, policy process, context and policy
      content that influenced how the SAs were designed and implemented. METHODS: We
      used qualitative analytical methods to study the Tanzanian experience with
      contracting- out. Data were drawn from document reviews and in-depth interviews
      with 39 key informants, including six interviews at the national and regional
      levels and 33 interviews at the district level. All interviews were audiotaped,
      transcribed and translated into English. Data were managed in NVivo (version
      10.0) and analyzed thematically. RESULTS: The institutional frameworks shaping
      the engagement of the government with NSPs are rooted in Tanzania's long history
      of public-private partnerships in the health sector. Demand for contractual
      arrangements emerged from both the government and the faith-based organizations
      that manage NSP facilities. Development partners provided significant technical
      and financial support, signaling their approval of the approach. Although
      districts gained the mandate and power to make contractual agreements with NSPs,
      financing the contracts remained largely dependent on donor funds via central
      government budget support. Delays in reimbursements, limited financial and
      technical capacity of local government authorities and lack of trust between the
      government and private partners affected the implementation of the contractual
      arrangements. CONCLUSIONS: Tanzania's central government needs to further develop
      the technical and financial capacity necessary to better support districts in
      establishing and financing contractual agreements with NSPs for primary health
      care services. Furthermore, forums for continuous dialogue between the government
      and contracted NSPs should be fostered in order to clarify the expectations of
      all parties and resolve any misunderstandings.

PMID- 30286765
TI  - Rhomboid domain-containing protein 1 promotes breast cancer progression by
      regulating the p-Akt and CDK2 levels.
AB  - BACKGROUND: Our previous work revealed that rhomboid domain-containing protein 1
      (RHBDD1) participates in the modulation of cell growth and apoptosis in
      colorectal cancer cells. This study aimed to investigate the function of RHBDD1
      in regulating breast cancer progression and its underlying molecular basis.
      METHODS: Immunohistochemistry was performed to evaluate RHBDD1 expression in 116
      breast cancer tissue and 39 adjacent normal tissue and expression of RHBDD1,
      phospho-Akt (p-Akt) and cyclin-dependent kinase 2 (CDK2) in the same 84 breast
      cancer specimens. RHBDD1-knock-out cells were established using breast cancer
      cell lines. In vitro studies were carried out to estimate the function of RHBDD1
      in cell proliferation, migration and invasion. Fluorescence microscopy assay and
      flow cytometric analysis were used to measure apoptosis and cell cycle
      regulation. RNA sequencing and western blot analysis were used to investigate the
      molecular mechanisms of RHBDD1. RESULTS: RHBDD1 was highly up-regulated in breast
      cancer tissue compared with that in normal tissue and associated with
      pathological tumor (pT) stage, pathological tumor-node-metastasis (pTNM) stage
      and estrogen receptor (ER) expression. RHBDD1 up-regulation was associated with
      poor prognosis in several subtypes of breast cancer. Deletion of RHBDD1 promoted
      apoptosis and suppressed proliferation, migration and invasion in breast cancer
      cells. RHBDD1 deletion suppressed Akt activation and decreased CDK2 protein level
      via proteasome pathway, thus inhibited cell cycle progression and G1/S phase
      transition. Moreover, the protein level of RHBDD1, p-Akt and CDK2 was
      significantly positively correlated in breast cancer tissue. CONCLUSIONS: Our
      study reveals that RHBDD1 promotes breast cancer progression by regulating p-Akt
      and CDK2 protein levels, and might be a potential biomarker and prognostic
      indicator for breast cancer patients.

PMID- 30286768
TI  - The effects of vitamin D supplementation on metabolic profiles and gene
      expression of insulin and lipid metabolism in infertile polycystic ovary syndrome
      candidates for in vitro fertilization.
AB  - BACKGROUND: Vitamin D deficiency in women diagnosed with polycystic ovary
      syndrome (PCOS) remarkably decreases the chance of pregnancy, which might be
      related to its impact on metabolic abnormalities in these patients. It is
      hypothesized that vitamin D supplementation influences metabolic profile of these
      patients and indirectly might affect fertility and the outcomes. Therefore, this
      study was conducted to determine the effects of vitamin D supplementation on the
      levels of anti-Mullerian hormone (AMH), metabolic profiles, and gene expression
      of insulin and lipid metabolism in infertile women with PCOS who were candidate
      for in vitro fertilization (IVF). METHODS: This study was a randomized, double
      blinded, placebo-controlled trial conducted among 40 infertile women, aged 18-40
      years, diagnosed with PCOS and was candidate for IVF. Participants were randomly
      assigned into two intervention groups for receiving either 50,000 IU vitamin D or
      placebo (n = 20 each group) every other week for 8 weeks. Gene expression for
      insulin and lipid metabolism was conducted using peripheral blood mononuclear
      cells (PBMCs) of women with PCOS, via RT-PCR method. RESULTS: Vitamin D
      supplementation led to a significant reduction in serum AMH (- 0.7 +/- 1.2 vs. -
      0.1 +/- 0.5 ng/mL, P = 0.02), insulin levels (- 1.4 +/- 1.6 vs. -0.3 +/- 0.9
      MUIU/mL, P = 0.007), homeostatic model of assessment for insulin resistance (-
      0.3 +/- 0.3 vs. -0.1 +/- 0.2, P = 0.008), and a significant increase in
      quantitative insulin sensitivity check index (+ 0.009 +/- 0.01 vs. + 0.001 +/-
      0.004, P = 0.04), compared with the placebo. Moreover, following vitamin D
      supplementation there was a significant decrease in serum total- (- 5.1 +/- 12.6
      vs. + 2.9 +/- 10.9 mg/dL, P = 0.03) and LDL-cholesterol levels (- 4.5 +/- 10.3
      vs. + 2.5 +/- 10.6 mg/dL, P = 0.04) compared with the placebo. CONCLUSION:
      Overall, the findings of this trial supported that 50,000 IU vitamin D
      supplementation every other week for 8 weeks had beneficial effects on insulin
      metabolism, and lipid profile of infertile women with PCOS who are candidate for
      IVF. These benefits might not be evident upon having sufficient vitamin D levels.
      TRIAL REGISTRATION: This study was retrospectively registered in the Iranian
      website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir :
      IRCT20170513033941N27).

PMID- 30286769
TI  - The systemic immune-inflammation index is an independent predictor of survival
      for metastatic colorectal cancer and its association with the lymphocytic
      response to the tumor.
AB  - BACKGROUND: Systemic inflammation and immune dysfunction has been proved to be
      significantly associated with cancer progression and metastasis in many cancer
      types, including colorectal cancer. We examined the prognostic significance of
      the systemic immune-inflammation index (SII) in patients with metastatic
      colorectal cancer (mCRC) and the relationship between the lymphocytic response to
      the tumor and this index. METHODS: This retrospective study evaluated 240
      consecutive patients with newly diagnosed stage IV mCRC who underwent surgical
      resection. The SII values were calculated based on preoperative laboratory data
      regarding platelet, neutrophil, and lymphocyte counts. Tumor-infiltrating
      lymphocytes were evaluated using the surgical specimens. The overall survival and
      their 95% confidence interval (95% CI) were estimated by regression analyses and
      the Kaplan-Meier method. RESULTS: After a mean follow-up of 26.7 (1.1-92.4)
      months, 146 patients (60.8%) died. In the univariate analysis, a high SII was
      significantly associated with poor overall survival (P = 0.009). The
      multivariable analysis also confirmed that a high SII was independently
      associated with poor overall survival (hazard ratio: 1.462, 95% confidence
      interval 1.049-2.038, P = 0.025). The SII value was significantly correlated with
      the TILs value at the tumor's center (P = 0.04), but not at the invasive margin
      (P = 0.39). When we evaluated overall survival for groupings of the tumor
      infiltrating lymphocytes and SII values, we identified three distinct prognostic
      groups. The group with low tumor-infiltrating lymphocyte values and high SII
      values had the worst prognosis. CONCLUSIONS: A high SII value independently
      predicts poor clinical outcomes among patients with mCRC. In addition, combining
      the lymphocytic response to the tumor and SII could further enhance
      prognostication for mCRC.

PMID- 30286771
TI  - Contracting non-state providers for universal health coverage: learnings from
      Africa, Asia, and Eastern Europe.
AB  - BACKGROUND: Formal engagement with non-state providers (NSP) is an important
      strategy in many low-and-middle-income countries for extending coverage of
      publicly financed health services. The series of country studies reviewed in this
      paper - from Afghanistan, Bangladesh, Bosnia & Herzegovina, Ghana, South Africa,
      Tanzania and Uganda - provide a unique opportunity to understand the dynamics of
      NSP engagement in different contexts. METHODS: A standard template was developed
      and used to summarize the main findings from the country studies. The summaries
      were then organized according to emergent themes and a narrative built around
      these themes. RESULTS: Governments contracted NSPs for a variety of reasons -
      limited public sector capacity, inability of public sector services to reach
      certain populations or geographic areas, and the widespread presence of NSPs in
      the health sector. Underlying these reasons was a recognition that purchasing
      services from NSPs was necessary to increase coverage of health services. Yet,
      institutional NSPs faced many service delivery challenges. Like the public
      sector, institutional NSPs faced challenges in recruiting and retaining health
      workers, and ensuring service quality. Properly managing relationships between
      all actors involved was critical to contracting success and the role of NSPs as
      strategic partners in achieving national health goals. Further, the relationship
      between the central and lower administrative levels in contract management, as
      well as government stewardship capacity for monitoring contractual performance
      were vital for NSP performance. CONCLUSION: For countries with a sizeable NSP
      sector, making full use of the available human and other resources by contracting
      NSPs and appropriately managing them, offers an important way for expanding
      coverage of publicly financed health services and moving towards universal health
      coverage.

PMID- 30286770
TI  - Factors influencing performance by contracted non-state providers implementing a
      basic package of health services in Afghanistan.
AB  - BACKGROUND: In 2002 Afghanistan's Ministry of Public Health (MoPH) and its
      development partners initiated a new paradigm for the health sector by electing
      to Contract-Out (CO) the Basic Package of Health Services (BPHS) to non-state
      providers (NSPs). This model is generally regarded as successful, but literature
      is scarce that examines the motivations underlying implementation and factors
      influencing program success. This paper uses relevant theories and qualitative
      data to describe how and why contracting out delivery of primary health care
      services to NSPs has been effective. The main aim of this study was to assess the
      contextual, institutional, and contractual factors that influenced the
      performance of NSPs delivering the BPHS in Afghanistan. METHODS: The qualitative
      study design involved individual in-depth interviews and focus group discussions
      conducted in six provinces of Afghanistan, as well as a desk review. The
      framework for assessing key factors of the contracting mechanism proposed by Liu
      et al. was utilized in the design, data collection and data analysis. RESULTS:
      While some contextual factors facilitated the CO (e.g. MoPH leadership, NSP
      innovation and community participation), harsh geography, political interference
      and insecurity in some provinces had negative effects. Contractual factors, such
      as effective input and output management, guided health service delivery.
      Institutional factors were important; management capacity of contracted NSPs
      affects their ability to deliver outcomes. Effective human resources and
      pharmaceutical management were notable elements that contributed to the
      successful delivery of the BPHS. The contextual, contractual and institutional
      factors interacted with each other. CONCLUSION: Three sets of factors influenced
      the implementation of the BPHS: contextual, contractual and institutional. The
      MoPH should consider all of these factors when contracting out the BPHS and other
      functions to NSPs. Other fragile states and countries emerging from a period of
      conflict could learn from Afghanistan's example in contracting out primary health
      care services, keeping in mind that generic or universal contracting policies
      might not work in all geographical areas within a country or between countries.

PMID- 30286772
TI  - Emergence of three general practitioner contracting-in models in South Africa: a
      qualitative multi-case study.
AB  - BACKGROUND: The general practitioner contracting initiative (GPCI) is a health
      systems strengthening initiative piloted in the first phase of national health
      insurance (NHI) implementation in South Africa as it progresses towards universal
      health coverage (UHC). GPCI aimed to address the shortage of doctors in the
      public sector by contracting-in private sector general practitioners (GPs) to
      render services in public primary health care clinics. This paper explores the
      early inception and emergence of the GPCI. It describes three models of
      contracting-in that emerged and interrogates key factors influencing their
      evolution. METHODS: This qualitative multi-case study draws on three cases. Data
      collection comprised document review, key informant interviews and focus group
      discussions with national, provincial and district managers as well as GPs (n =
      68). Walt and Gilson's health policy analysis triangle and Liu's conceptual
      framework on contracting-out were used to explore the policy content, process,
      actors and contractual arrangements involved. RESULTS: Three models of
      contracting-in emerged, based on the type of purchaser: a centralized-purchaser
      model, a decentralized-purchaser model and a contracted-purchaser model. These
      models are funded from a single central source but have varying levels of
      involvement of national, provincial and district managers. Funds are channelled
      from purchaser to provider in slightly different ways. Contract formality
      differed slightly by model and was found to be influenced by context and type of
      purchaser. Conceptualization of the GPCI was primarily a nationally-driven
      process in a context of high-level political will to address inequity through NHI
      implementation. Emergence of the models was influenced by three main factors,
      flexibility in the piloting process, managerial capacity and financial management
      capacity. CONCLUSION: The GPCI models were iterations of the centralized
      purchaser model. Emergence of the other models was strongly influenced by
      purchaser capacity to manage contracts, payments and recruitment processes.
      Findings from the decentralized-purchaser model show importance of local context,
      provincial capacity and experience on influencing evolution of the models. Whilst
      contract characteristics need to be well defined, allowing for adaptability to
      the local context and capacity is critical. Purchaser capacity, existing systems
      and institutional knowledge and experience in contracting and financial
      management should be considered before adopting a decentralized implementation
      approach.

PMID- 30286774
TI  - Tibiofemoral joint contact area and stress after single-bundle anterior cruciate
      ligament reconstruction with transtibial versus anteromedial portal drilling
      techniques.
AB  - BACKGROUND: During single-bundle ACLR, femoral tunnel location plays an important
      role in restoring the intact knee mechanisms, whereas malplacement of the tunnel
      was cited as the most common cause of knee instability. The objective of this
      study is to evaluate, objectively, the tibiofemoral contact area and stress after
      single-bundle (SB) anterior cruciate ligament reconstruction (ACLR) with femoral
      tunnel positions drilled by transtibial (TT) or anteromedial (AM) portal
      techniques. METHODS: Seven fresh human cadaveric knees underwent ACLR by the use
      of TT or AM portal techniques in a randomized order. These specimens were reused
      for ACL-R (TT and AM). The tibiofemoral contact area and stresses were gauged by
      an electronic stress-sensitive film inserted into the joint space. The knee was
      under the femoral axial compressive load of 1000 N using a biomechanics testing
      machine at 0 degrees , 10 degrees , 20 degrees , and 30 degrees  of flexion.
      Three conditions were compared: (1) intact ACL, (2) ACLR by the use of the TT
      method, and (3) ACLR by the use of the AM portal method. RESULTS: Compared with
      AM portal ACL-reconstructed knees, a significantly decreased tibiofemoral contact
      area on the medial compartment was detected in the TT ACL-reconstructed knees at
      20 degrees of knee flexion (P = .047). Compared with the intact group, the TT
      ACLR group showed a higher mean stress at 20 degrees  and 30 degrees  of flexion
      on the medial compartments (P = .001, P = .003, respectively), while the AM
      portal ACLR group showed no significant differences at 30 degrees  of flexion (P
      = .073). The TT ACLR group also showed a higher mean maximum stress at 20 degrees
      of flexion on the medial compartments (P = .047), while the AM portal ACLR group
      showed no significant differences at this angle(P = .319). DISCUSSION: The
      alternation of the tibiofemoral joint contact area and stress in reconstructed
      knees may be caused by the mismatch of the tibiofemoral joint during knee
      movement procedures compared with intact knees. CONCLUSIONS: SB ACLR by the use
      of the AM portal method and TT method both alter the tibiofemoral contact area
      and stress when compared with the intact knee. When compared with the TT
      technique, ACLR by the AM portal technique more closely restores the intact
      tibiofemoral contact area and stress at low flexion angles.

PMID- 30286773
TI  - The 3D Genome Browser: a web-based browser for visualizing 3D genome organization
      and long-range chromatin interactions.
AB  - Here, we introduce the 3D Genome Browser, http://3dgenome.org , which allows
      users to conveniently explore both their own and over 300 publicly available
      chromatin interaction data of different types. We design a new binary data format
      for Hi-C data that reduces the file size by at least a magnitude and allows users
      to visualize chromatin interactions over millions of base pairs within seconds.
      Our browser provides multiple methods linking distal cis-regulatory elements with
      their potential target genes. Users can seamlessly integrate thousands of other
      omics data to gain a comprehensive view of both regulatory landscape and 3D
      genome structure.

PMID- 30286775
TI  - Psychological symptoms and the MCID of the DASH score in shoulder surgery.
AB  - BACKGROUND: Psychological symptoms are frequently present in patients scheduled
      for shoulder surgery. The perception of functional disability, activity level and
      pain in the shoulder is negatively influenced by psychological symptoms, which
      leads to higher scores of the Disabilities of the Arm, Shoulder and Hand (DASH)
      questionnaire. The aim of this study was to determine the influence of
      psychological symptoms on the minimal clinically important difference (MCID) of
      the DASH score in patients after shoulder surgery. METHODS: In this prospective
      longitudinal cohort study, 176 patients were included. Group 1 (32 patients) had
      symptoms of psychological disorders before and after surgery; group 2 had no
      symptoms of psychological disorders (110 patients). In the remaining patients (34
      patients), psychological disorders changed after surgery. Clinical outcome was
      measured with the change of DASH score and anchor questions for perceived
      improvement of pain and function after surgery. Symptoms of psychological
      disorders were identified with the Four-Dimensional Symptom Questionnaire. An
      anchor-based mean change score technique was used to determine the MCID of the
      DASH score. RESULTS: DASH scores before and 12 months after shoulder surgery were
      significantly higher in patients with symptoms of psychological disorders; change
      of DASH score was not different between the two groups. The MCID of the DASH
      score was 13.0 [SD 20.7] in the group with symptoms of psychological disorders
      and 12.7 [SD 17.6] in the group with no symptoms of psychological disorders. We
      observed no difference (p = 0.559) in the MCID between the group with and the
      group without symptoms of psychological disorders. CONCLUSION: Symptoms of
      psychological disorders had a negative effect on the DASH score but no influence
      on the MCID of the DASH score. The DASH score could be used in future studies to
      assess the influence of psychological factors on the clinical outcome of
      treatment.

PMID- 30286776
TI  - Automated functional upper limb evaluation of patients with Friedreich ataxia
      using serious games rehabilitation exercises.
AB  - BACKGROUND: Friedreich ataxia (FRDA) is a disease with neurological and systemic
      involvement. Clinical assessment tools commonly used for FRDA become less
      effective in evaluating decay in patients with advanced FRDA, particularly when
      they are in a wheelchair. Further motor worsening mainly impairs upper limb
      function. In this study, we tested if serious games (SG) developed for
      rehabilitation can be used as an assessment tool for upper limb function even in
      patients with advanced FRDA. METHODS: A specific SG has been developed for
      physical rehabilitation of patients suffering from neurologic diseases. The use
      of this SG, coupled with Kinect sensor, has been validated to perform functional
      evaluation of the upper limbs with healthy subjects across lifespan. Twenty-seven
      FRDA patients were included in the study. Patients were invited to perform upper
      limb rehabilitation exercises embedded in SG. Motions were recorded by the Kinect
      and clinically relevant parameters were extracted from the collected motions. We
      tested if the existence of correlations between the scores from the serious games
      and the severity of the disease using clinical assessment tools commonly used for
      FRDA. Results of patients were compared with a group a healthy subjects of
      similar age. RESULTS: Very highly significant differences were found for time
      required to perform the exercise (increase of 76%, t(68) = 7.22, P < 0.001) and
      for accuracy (decrease of 6%, t(68) = - 3.69, P < 0.001) between patients and
      healthy subjects. Concerning the patients significant correlations were found
      between age and time (R = 0.65, p = 0.015), accuracy (R = - 0.75, p = 0.004) and
      the total displacement of upper limbs. (R = 0.55, p = 0.031). Statistically
      significant correlations were found between the age of diagnosis and speed
      related parameters. CONCLUSIONS: The results of this study indicate that SG
      reliably captures motor impairment of FRDA patients due to cerebellar and
      pyramidal involvement. Results also show that functional evaluation of FRDA
      patients can be performed during rehabilitation therapy embedded in games with
      the patient seated in a wheelchair. TRIAL REGISTRATION: The study was approved as
      a component of the EFACTS study ( Clinicaltrials.gov identifier NCT02069509 ,
      registered May 2010) by the local institutional Ethics Committee (ref.
      P2010/132).

PMID- 30286777
TI  - Accelerated vs. conventionally fractionated adjuvant radiotherapy in high-risk
      head and neck cancer: a meta-analysis.
AB  - BACKGROUND: Adjuvant radiotherapy in advanced head and neck squamous cell cancer
      (HNSCC) reduces the risk of local-regional failure and most likely increases the
      survival rate. Patients at high risk for tumor recurrence may benefit from more
      aggressive altered fractionation schedules in order to reduce the overall time
      from surgery to completion of radiotherapy. Here, we reviewed the results of six
      randomized trials addressing the above hypothesis. METHODS: In the six trials of
      interest, a total of 988 patients with locally advanced HNSCC were randomly
      assigned to receive either accelerated or conventionally fractionated adjuvant
      radiotherapy. Hazard ratios (HR) were extracted from available publications for
      local-regional control, distant metastasis as well as overall-, cancer specific-
      and disease-free survival. Meta-analysis of the effect sizes was performed using
      fixed and random effect models. Acute and late side effects were categorized and
      summarized for comparison. RESULTS: Accelerated radiotherapy did not improve the
      loco-regional control (n = 988, HR = 0.740, CI = 0.48-1.13, p = 0.162),
      progression-free survival (HR = 0.89, CI = 0.76-1.04, p = 0.132) or overall
      survival (HR = 0.88, CI = 0.75-1.04, p = 0.148) significantly. Acute confluent
      mucositis occurred with significant higher frequency with accelerated
      radiotherapy. Late side effects did not differ significantly in either group.
      CONCLUSION: Accelerated radiotherapy does not result in a significant improvement
      of loco-regional control or overall survival in high-risk patients. Acute but not
      late radiation toxicity were more frequent with the accelerated RT technique. In
      clinical practice accelerated postoperative radiation therapy might be a suitable
      option only for a subset of patients.

PMID- 30286778
TI  - Reoperation for isolated rheumatic tricuspid regurgitation.
AB  - BACKGROUND: The reoperation for isolated tricuspid regurgitation in rheumatic
      population is rare and still unclear and controversial because of the rarity of
      publications. The aim of this study was to analyze short and long-term results
      and outcome of tricuspid valve surgery after left-sided valve surgery in
      rheumatic patients. METHODS: Twenty six consecutive rheumatic patients who
      underwent isolated tricuspid valve surgery after left-sided valve surgery between
      January 2000 and January2017 were retrospectively registered in the study. The
      mean age was 48.2 +/- 8.6 years with 8.3% as sex-ratio (M/F). EuroSCORE was 6.1
      +/- 5 (range 2.5 to 24.1). The mechanism of tricuspid regurgitation was
      functional and organic in respectively 14 (53.8%) and 12 cases (46.2%). Ten
      patients (38.5%) had previous tricuspid valve repair. Surgery consisted of 15
      ring annuloplasty and 11 tricuspid valve replacement (5 bioprostheses and 6
      mechanical prostheses). Follow-up was 96.1% complete, with a mean follow-up of
      55.6 +/- 38.8 months (range 1 to 165). RESULTS: The operative mortality rate was
      15.4% (n = 4) and the cumulative survival at 1, 5 and 10 years was respectively
      80% +/- 8%, 75.6% +/- 8.7% and 67.2% +/- 11.1% with no significant difference at
      8 years between tricuspid valve replacement (80% +/- 12.6%) and repair (57.6% +/-
      16.1%) (p = 0.5). Multivariable Cox regression analysis revealed that ascites
      (HR, 5.8; p = 0.01), and right ventricular dysfunction (HR, 0.94; p = 0.001) were
      predictors of major adverse cardiac events. There were no recurrence of tricuspid
      regurgitation and no structural or non-structural deterioration of valvular
      prostheses. CONCLUSION: The reoperation of rheumatic tricuspid regurgitation
      should be considered before the installation of complications such as right
      ventricular dysfunction and major signs of right heart failure. Despite the
      superiority of repair techniques, tricuspid valve replacement should not be
      banished.

PMID- 30286779
TI  - Inhibition of STAT3 blocks protein synthesis and tumor metastasis in osteosarcoma
      cells.
AB  - BACKGROUND: Osteosarcoma is the most common bone cancer. Despite advances,
      molecular mechanisms associated with osteosarcoma have not been fully understood.
      Hence, an effective treatment for osteosarcoma has yet to be developed. Even
      though signal transducer and activator of transcription3 (STAT3) has been
      implicated, its role in pathogenesis of osteosarcoma is not fully determined. In
      this study, we investigated the antitumor effect of napabucasin (NP) (BBI608), an
      inhibitor of STAT3 on osteosarcoma in vitro and in vivo and studied the
      underlying molecular mechanism. METHODS: Cell viability, colony formation,
      apoptosis, tumor growth and metastasis assays were performed to examine the
      effect of NP on osteosarcoma in vitro and in vivo. Real-time RT-PCR, western
      analysis, immunofluorescence and reporter assays were used to monitor the
      expression and activity of proteins and underlying molecular pathways. Protein
      synthesis, co-immunoprecipitation and CAP binding assays were carried out to
      understand NP-mediated mechanism of actions in osteosarcoma cells. RESULTS: Our
      results show that NP treatment decreases cell viability and induces apoptosis in
      several osteosarcoma cell lines. NP treatment suppresses both expression and
      phosphorylation of STAT3 in addition to blocking STAT3-mediated transcription and
      downstream target proteins in osteosarcoma cells. Furthermore, NP inhibits
      protein synthesis through regulation of the eukaryotic initiation factor 4E
      (eIF4E) and eIF4E-binding protein 1 (4E-BP1). NP also inhibits the progression of
      osteosarcoma tumors and metastasis in vivo in an orthotopic tibial model of
      osteosarcoma. CONCLUSIONS: Taken together, our investigation reveals that NP acts
      through a novel mechanism and inhibits osteosarcoma growth and metastasis, and
      could be investigated clinically for treating osteosarcoma patients alone or in
      combination with other drugs.

PMID- 30286780
TI  - Growth factor independence 1 expression in myeloma cells enhances their growth,
      survival, and osteoclastogenesis.
AB  - BACKGROUND: In spite of major advances in treatment, multiple myeloma (MM) is
      currently an incurable malignancy due to the emergence of drug-resistant clones.
      We previously showed that MM cells upregulate the transcriptional repressor,
      growth factor independence 1 (Gfi1), in bone marrow stromal cells (BMSCs) that
      induces prolonged inhibition of osteoblast differentiation. However, the role of
      Gfi1 in MM cells is unknown. METHODS: Human primary CD138+ and BMSC were purified
      from normal donors and MM patients' bone marrow aspirates. Gfi1 knockdown and
      overexpressing cells were generated by lentiviral-mediated shRNA.
      Proliferation/apoptosis studies were done by flow cytometry, and protein levels
      were determined by Western blot and/or immunohistochemistry. An experimental MM
      mouse model was generated to investigate the effects of MM cells overexpressing
      Gfi1 on tumor burden and osteolysis in vivo. RESULTS: We found that Gfi1
      expression is increased in patient's MM cells and MM cell lines and was further
      increased by co-culture with BMSC, IL-6, and sphingosine-1-phosphate. Modulation
      of Gfi1 in MM cells had major effects on their survival and growth. Knockdown of
      Gfi1 induced apoptosis in p53-wt, p53-mutant, and p53-deficient MM cells, while
      Gfi1 overexpression enhanced MM cell growth and protected MM cells from
      bortezomib-induced cell death. Gfi1 enhanced cell survival of p53-wt MM cells by
      binding to p53, thereby blocking binding to the promoters of the pro-apoptotic
      BAX and NOXA genes. Further, Gfi1-p53 binding could be blocked by HDAC
      inhibitors. Importantly, inoculation of MM cells overexpressing Gfi1 in mice
      induced increased bone destruction, increased osteoclast number and size, and
      enhanced tumor growth. CONCLUSIONS: These results support that Gfi1 plays a key
      role in MM tumor growth, survival, and bone destruction and contributes to
      bortezomib resistance, suggesting that Gfi1 may be a novel therapeutic target for
      MM.

PMID- 30286781
TI  - Predicting microRNA targeting efficacy in Drosophila.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short regulatory RNAs that derive from hairpin
      precursors. Important for understanding the functional roles of miRNAs is the
      ability to predict the messenger RNA (mRNA) targets most responsive to each
      miRNA. Progress towards developing quantitative models of miRNA targeting in
      Drosophila and other invertebrate species has lagged behind that of mammals due
      to the paucity of datasets measuring the effects of miRNAs on mRNA levels.
      RESULTS: We acquired datasets suitable for the quantitative study of miRNA
      targeting in Drosophila. Analyses of these data expanded the types of regulatory
      sites known to be effective in flies, expanded the mRNA regions with detectable
      targeting to include 5' untranslated regions, and identified features of site
      context that correlate with targeting efficacy in fly cells. Updated evolutionary
      analyses evaluated the probability of conserved targeting for each predicted site
      and indicated that more than a third of the Drosophila genes are preferentially
      conserved targets of miRNAs. Based on these results, a quantitative model was
      developed to predict targeting efficacy in insects. This model performed better
      than existing models, and it drives the most recent version, v7, of
      TargetScanFly. CONCLUSIONS: Our evolutionary and functional analyses expand the
      known scope of miRNA targeting in flies and other insects. The existence of a
      quantitative model that has been developed and trained using Drosophila data will
      provide a valuable resource for placing miRNAs into gene regulatory networks of
      this important experimental organism.

PMID- 30286783
TI  - Autosomal-dominant transthyretin (TTR)-related amyloidosis is not a frequent CMT2
      neuropathy "in disguise".
AB  - Transthyretin (TTR)-related familial amyloid polyneuropathy (TTR-FAP) is a life
      threatening autosomal dominant, systemic disease. First symptoms usually occur
      from the second to over sixth decade of life with a length-dependent axonal
      neuropathy with prominent involvement of the small fibers and multi-organ
      systemic failure.Early diagnosis is pivotal for effective therapeutic options,
      but it is hampered by the heterogeneity of the clinical spectrum which can lead
      to misdiagnosis with other neurological condition/disorder such as axonal sensory
      motor neuropathy (CMT2) as described in literature.The aim of our study was to
      search for TTR mutations in a large cohort of selected undiagnosed axonal sensory
      motor neuropathy patients to establish if misdiagnosis is frequent or rare in the
      Italian population.No TTR pathogenic variants were found in our cohort. In
      conclusion, our study shows that TTR testing not should be straightforward
      recommended in CMT2 patients but only when "red flags" TTR's features are
      present.

PMID- 30286782
TI  - Maternal breast cancer risk in relation to birthweight and gestation of her
      offspring.
AB  - BACKGROUND: Parity and age at first pregnancy are well-established risk factors
      for breast cancer, but the effects of other characteristics of pregnancies are
      uncertain and the literature is inconsistent. METHODS: In a cohort of 83,451
      parous women from the general population of the UK, which collected detailed
      information on each pregnancy and a wide range of potential confounders, we
      investigated the associations of length of gestation and birthweight of offspring
      in a woman's pregnancies with her breast cancer risk, adjusting for a full range
      of non-reproductive as well as reproductive risk factors unlike in previous large
      studies. RESULTS: Gestation of the first-born offspring was significantly
      inversely related to the risk of pre-menopausal breast cancer (p trend = 0.03;
      hazard ratio (HR) for 26-31 compared with 40-41 weeks, the baseline group, =
      2.38, 95% confidence interval (CI) 1.26-4.49), and was borderline significantly
      related to risk of breast cancer overall (p trend = 0.05). Risk was significantly
      raised in mothers of high birthweight first-born (HR for breast cancer overall =
      1.53, 95% CI 1.06-2.21 for >= 4500 g compared with 3000-3499 g, the baseline
      group). For gestation and birthweight of most recent birth, there were no clear
      effects. Analyses without adjustment for confounders (other than age) gave
      similar results. CONCLUSIONS: Our data add to evidence that short gestation
      pregnancies may increase the risk of breast cancer, at least pre-menopausally,
      perhaps by hormonal stimulation and breast proliferation early in pregnancy
      without the opportunity for the differentiation that occurs in late pregnancy.
      High birthweight first pregnancies may increase breast cancer risk, possibly
      through the association of birthweight with oestrogen and insulin-like growth
      factor 1 levels.

PMID- 30286785
TI  - Counseling practice of community pharmacists for diabetes mellitus patients in
      Addis Ababa, Ethiopia.
AB  - OBJECTIVE: Pharmacists monitor diabetic patients more often than any other
      healthcare providers. It is important that they have appropriate counseling
      practice on diabetes mellitus management. The aim of this study is to assess the
      counseling practice of community pharmacists for diabetes mellitus patients in
      Addis Ababa, Ethiopia. RESULTS: Among 300 community pharmacy professionals, 58.3%
      were male. Nearly half of the community pharmacy professionals delivered
      appropriate counselling service on the appropriate time to administer each oral
      anti-diabetic drug and missed oral dose. Only 15.3% of the community pharmacy
      professionals gave proper counselling on the importance of continuous screening
      for nephropathy, retinopathy, and neuropathy.

PMID- 30286784
TI  - The Italian neuromuscular registry: a coordinated platform where patient
      organizations and clinicians collaborate for data collection and multiple usage.
AB  - BACKGROUND: The worldwide landscape of patient registries in the neuromuscular
      disease (NMD) field has significantly changed in the last 10 years, with the
      international TREAT-NMD network acting as strong driver. At the same time, the
      European Medicines Agency and the large federations of rare disease patient
      organizations (POs), such as EURORDIS, contributed to a great cultural change, by
      promoting a paradigm shift from product-registries to patient-centred registries.
      In Italy, several NMD POs and Fondazione Telethon undertook the development of a
      TREAT-NMD linked patient registry in 2009, with the referring clinical network
      providing input and support to this initiative through the years. This article
      describes the outcome of this joint effort and shares the experience gained.
      METHODS: The Italian NMD registry is based on an informatics technology platform,
      structured according to the most rigorous legal national and European
      requirements for management of patient sensitive data. A user-friendly web
      interface allows both direct patients and clinicians' participation. The
      platform's design permits expansion to incorporate new modules and new
      registries, and is suitable of interoperability with other international efforts.
      RESULTS: When the Italian NMD Registry was initiated, an ad hoc legal entity (NMD
      Registry Association) was devised to manage registries' data. Currently, several
      disease-specific databases are hosted on the platform. They collect molecular and
      clinical details of individuals affected by Duchenne or Becker muscular
      dystrophy, Charcot-Marie-Tooth disease, transthyretin type-familial amyloidotic
      polyneuropathy, muscle glycogen storage disorders, spinal and bulbar muscular
      atrophy, and spinal muscular atrophy. These disease-specific registries are at
      different stage of development, and the NMD Registry itself has gone through
      several implementation steps to fulfil different technical and governance needs.
      The new governance model is based on the agreement between the NMD Registry
      Association and the professional societies representing the Italian NMD clinical
      network. Overall, up to now the NMD registry has collected data on more than 2000
      individuals living with a NMD condition. CONCLUSIONS: The Italian NMD Registry is
      a flexible platform that manages several condition-specific databases and is
      suitable to upgrade. All stakeholders participate in its management, with clear
      roles and responsibilities. This governance model has been key to its success. In
      fact, it favored patient empowerment and their direct participation in research,
      while also engaging the expert clinicians of the Italian network in the
      collection of accurate clinical data according to the best clinical practices.

PMID- 30286787
TI  - The effects of dietary instruction on cardiovascular risk markers after smoking
      cessation: study protocol for a multicenter randomized controlled trial in Japan.
AB  - BACKGROUND: Weight gain frequently occurs after smoking cessation (SC); the risk
      of new-onset diabetes mellitus increases for several years after SC. However, no
      large-scale, randomized controlled trials have examined the effects of
      nutritional guidance on post-SC cardiovascular risk. The current trial will
      enroll individuals who successfully quit smoking with the help of a SC clinic and
      who gain weight, to determine the effects of nutritional guidance on
      cardiovascular, glucose, and lipid metabolism biomarkers. METHODS/DESIGN: This is
      a multicenter, prospective, parallel-group, randomized controlled trial. Some 250
      individuals who successfully quit smoking with the help of a SC clinic and who
      gain weight (an increase of >= 1.25% Body Mass Index (BMI) between the first and
      the fifth visit to the SC clinic) will be enrolled within 1 month of the final
      (fifth) visit to the SC clinic. These participants will be randomly assigned to
      an intervention group (125 individuals receiving nutritional guidance) or a
      control group (125 individuals not receiving nutritional guidance). A registered
      dietitian will provide nutritional guidance once every 3 months for a total of
      three sessions. The primary endpoint for this trial will be the level of
      adiponectin, a predictor of cardiovascular risk that reflects weight and smoking
      status. Secondary endpoints will be levels of cardiovascular, glucose, and lipid
      metabolism biomarkers, BMI, abdominal circumference, and the percentage of
      individuals who quit smoking for a prolonged period. DISCUSSION: This trial will
      determine the benefits of nutritional guidance with respect to post-SC weight
      gain. The findings should provide useful information for devising a quality
      protocol for SC education to prevent cardiovascular disease. TRIAL REGISTRATION:
      The study is registered at the University Hospital Medical Information Network
      Clinical Trials Registry ( UMIN000030282 ). Registered on 6 December 2017.

PMID- 30286786
TI  - The burden of low back pain among undergraduate physiotherapy students at the
      University of Zimbabwe: a cross-sectional study.
AB  - OBJECTIVE: Globally, non-specific low back pain (NSLBP) is a common cause of
      morbidity in all people including physiotherapy students. However, no study has
      investigated the problem among undergraduate physiotherapy students in Zimbabwe.
      This study was conducted, therefore, to provide evidence of the prevalence,
      clinical characteristics and consequences of recurrent NSLBP among undergraduate
      physiotherapy students at the University of Zimbabwe. RESULTS: The final sample
      had 90 participants, giving a study response rate of 97.8%. The median age of the
      participants was 22 years. The lifetime prevalence of NSLBP was 56.7% (n = 51)
      and the mean age of onset for NSLBP was 19.7 years (SD = 1.64 years). The 12
      month prevalence of recurrent NSLBP was 38.9% (n = 35). Of the 35, 20 (57.1%)
      experienced at least three episodes in the last 12 months. Each episode lasted
      for 1-7 days in most participants (n = 31, 88.6%). The mean intensity of
      recurrent episodes was 3.37 (SD = 1.43) measured on Visual Analogue Scale. Only 7
      (20%) experienced at least one functional limitation due to recurrent NSLBP.
      Additionally, only 2 (5.7%) sought medical treatment for the pain. However, 6
      (17.1%) had to be absent from the university secondary to recurrent NSLBP.

PMID- 30286788
TI  - A novel long noncoding RNA HOXC-AS3 mediates tumorigenesis of gastric cancer by
      binding to YBX1.
AB  - BACKGROUND: Recently, increasing evidence shows that long noncoding RNAs
      (lncRNAs) play a significant role in human tumorigenesis. However, the function
      of lncRNAs in human gastric cancer remains largely unknown. RESULTS: By using
      publicly available expression profiling data from gastric cancer and integrating
      bioinformatics analyses, we screen and identify a novel lncRNA, HOXC-AS3. HOXC
      AS3 is significantly increased in gastric cancer tissues and is correlated with
      clinical outcomes of gastric cancer. In addition, HOXC-AS3 regulates cell
      proliferation and migration both in vitro and in vivo. RNA-seq analysis reveals
      that HOXC-AS3 knockdown preferentially affects genes that are linked to
      proliferation and migration. Mechanistically, we find that HOXC-AS3 is obviously
      activated by gain of H3K4me3 and H3K27ac, both in cells and in tissues. RNA pull
      down mass spectrometry analysis identifies that YBX1 interacts with HOXC-AS3, and
      RNA-seq analysis finds a marked overlap in genes differentially expressed after
      YBX1 knockdown and those transcriptionally regulated by HOXC-AS3, suggesting that
      YBX1 participates in HOXC-AS3-mediated gene transcriptional regulation in the
      tumorigenesis of gastric cancer. CONCLUSIONS: Together, our data demonstrate that
      abnormal histone modification-activated HOXC-AS3 may play important roles in
      gastric cancer oncogenesis and may serve as a target for gastric cancer diagnosis
      and therapy.

PMID- 30286789
TI  - Empowering the detection of ChIP-seq "basic peaks" (bPeaks) in small eukaryotic
      genomes with a web user-interactive interface.
AB  - OBJECTIVE: bPeaks is a peak calling program to detect protein DNA-binding sites
      from ChIPseq data in small eukaryotic genomes. The simplicity of the bPeaks
      method is well appreciated by users, but its use via an R package is challenging
      and time-consuming for people without programming skills. In addition, user
      feedback has highlighted the lack of a convenient way to carefully explore bPeaks
      result files. In this context, the development of a web user interface represents
      an important added value for expanding the bPeaks user community. RESULTS: We
      developed a new bPeaks application (bPeaks App). The application allows the user
      to perform all the peak-calling analysis steps with bPeaks in a few mouse clicks
      via a web browser. We added new features relative to the original R package,
      particularly the possibility to import personal annotation files to compare the
      location of the detected peaks with specific genomic elements of interest of the
      user, in any organism, and a new organization of the result files which are
      directly manageable via a user-interactive genome browser. This significantly
      improves the ability of the user to explore all detected basic peaks in detail.

PMID- 30286790
TI  - Lessons from a comparison of immuno-chromatographic and chemiluminescent micro
      particle immunoassay in the diagnosis of syphilis.
AB  - OBJECTIVE: To synthesize lessons from comparison of results obtained from the
      immuno-chromatographic SD Bioline testing method and the chemiluminescent micro
      particle immunoassay Architect in the diagnosis of syphilis at Livingstone
      Central hospital laboratory. RESULTS: The specificity and sensitivity of SD
      Bioline syphilis 3.0 against the chemiluminescent immunoassay using the Architect
      syphilis Treponema pallidum (TP) was 85.3% and 91.3% respectively with
      substantial agreement between the two test methods (88%, K  = 0.76; p < 0.0005).
      We recommend further comprehensive study with a larger sample size and clinical
      details to ascertain the validity of our findings. We also recommend using a non
      treponemal test with the current treponemal tests being used to aid diagnosis.

PMID- 30286791
TI  - Deep proteomic network analysis of Alzheimer's disease brain reveals alterations
      in RNA binding proteins and RNA splicing associated with disease.
AB  - BACKGROUND: The complicated cellular and biochemical changes that occur in brain
      during Alzheimer's disease are poorly understood. In a previous study we used an
      unbiased label-free quantitative mass spectrometry-based proteomic approach to
      analyze these changes at a systems level in post-mortem cortical tissue from
      patients with Alzheimer's disease (AD), asymptomatic Alzheimer's disease
      (AsymAD), and controls. We found modules of co-expressed proteins that correlated
      with AD phenotypes, some of which were enriched in proteins identified as risk
      factors for AD by genetic studies. METHODS: The amount of information that can be
      obtained from such systems-level proteomic analyses is critically dependent upon
      the number of proteins that can be quantified across a cohort. We report here a
      new proteomic systems-level analysis of AD brain based on 6,533 proteins measured
      across AD, AsymAD, and controls using an analysis pipeline consisting of isobaric
      tandem mass tag (TMT) mass spectrometry and offline prefractionation. RESULTS:
      Our new TMT pipeline allowed us to more than double the depth of brain proteome
      coverage. This increased depth of coverage greatly expanded the brain protein
      network to reveal new protein modules that correlated with disease and were
      unrelated to those identified in our previous network. Differential protein
      abundance analysis identified 350 proteins that had altered levels between AsymAD
      and AD not caused by changes in specific cell type abundance, potentially
      reflecting biochemical changes that are associated with cognitive decline in AD.
      RNA binding proteins emerged as a class of proteins altered between AsymAD and
      AD, and were enriched in network modules that correlated with AD pathology. We
      developed a proteogenomic approach to investigate RNA splicing events that may be
      altered by RNA binding protein changes in AD. The increased proteome depth
      afforded by our TMT pipeline allowed us to identify and quantify a large number
      of alternatively spliced protein isoforms in brain, including AD risk factors
      such as BIN1, PICALM, PTK2B, and FERMT2. Many of the new AD protein network
      modules were enriched in alternatively spliced proteins and correlated with
      molecular markers of AD pathology and cognition. CONCLUSIONS: Further analysis of
      the AD brain proteome will continue to yield new insights into the biological
      basis of AD.

PMID- 30286792
TI  - Tri-methylation of ATF7IP by G9a/GLP recruits the chromodomain protein MPP8.
AB  - BACKGROUND: G9a and the related enzyme GLP were originally identified as histone
      lysine methyltransferases and then shown to also methylate several other non
      histone proteins. RESULTS: Here, we performed a comprehensive screen to identify
      their substrates in mouse embryonic stem cells (mESCs). We identified 59
      proteins, including histones and other known substrates. One of the identified
      substrates, activating transcriptional factor 7-interacting protein 1 (ATF7IP),
      is tri-methylated at a histone H3 lysine 9 (H3K9)-like mimic by the G9a/GLP
      complex, although this complex mainly introduces di-methylation on H3K9 and DNA
      ligase 1 (LIG1) K126 in cells. The catalytic domain of G9a showed a higher
      affinity for di-methylated lysine on ATF7IP than LIG1, which may create different
      methylation levels of different substrates in cells. Furthermore, we found that M
      phase phosphoprotein 8 (MPP8), known as a H3K9me3-binding protein, recognizes
      methylated ATF7IP via its chromodomain. MPP8 is also a known component of the
      human silencing hub complex that mediates silencing of transgenes via SETDB1
      recruitment, which is a binding partner of ATF7IP. Although the interaction
      between ATF7IP and SETDB1 does not depend on ATF7IP methylation, we found that
      induction of SETDB1/MPP8-mediated reporter-provirus silencing is delayed in mESCs
      expressing only an un-methylatable mutant of ATF7IP. CONCLUSIONS: Our findings
      provide new insights into the roles of lysine methylation in non-histone
      substrates which are targeted by the G9a/GLP complex and suggest a potential
      function of ATF7IP methylation in SETDB1/MPP8-mediated transgene silencing.

PMID- 30286793
TI  - E2F2 directly regulates the STAT1 and PI3K/AKT/NF-kappaB pathways to exacerbate
      the inflammatory phenotype in rheumatoid arthritis synovial fibroblasts and mouse
      embryonic fibroblasts.
AB  - BACKGROUND: Expression of E2F transcription factor 2 (E2F2), a transcription
      factor related to the cell cycle, is abnormally high in rheumatoid arthritis
      synovial fibroblasts (RASFs). Deregulated expression of E2F2 leads to abnormal
      production of proinflammatory cytokines, such as interleukin (IL)-1alpha, IL
      1beta, and tumor necrosis factor (TNF)-alpha in RASFs. However, the underlying
      mechanism by which E2F2 regulates expression of IL-1alpha, IL-1beta, and TNF
      alpha has not been fully elucidated. This study aimed to elucidate this mechanism
      and confirm the pathological roles of E2F2 in rheumatoid arthritis (RA). METHODS:
      E2f2 knockout (KO) and wild-type (WT) mice were injected with collagen to induce
      RA. Cytokine production was assessed by quantitative real-time polymerase chain
      reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Western blot
      and qRT-PCR were performed to evaluate the effect of E2F2 on signaling pathway
      activity. Chromatin immunoprecipitation (ChIP)-PCR and luciferase assays were
      used to detect the transcriptional activity of target genes of E2F2. Nuclear
      translocation of STAT1 and p65 were assayed by Western blot, co
      immunoprecipitation (co-IP), and immunofluorescence experiments. RESULTS: The
      occurrence and severity of collagen-induced arthritis were decreased in E2f2-KO
      mice compared with WT mice. The expression of IL-1alpha, IL-1beta, and TNF-alpha
      was also suppressed in mouse embryonic fibroblasts (MEFs) from E2f2-KO mice and
      RASFs with E2F2 knocked down. Mechanistically, we found that E2F2 can upregulate
      the expression of STAT1 and MyD88 through direct binding to their promoters,
      facilitate the formation of STAT1/MyD88 complexes, and consequently activate AKT.
      However, silencing STAT1/MyD88 or inactivating AKT significantly attenuated the
      induction of IL-1alpha, IL-1beta, and TNF-alpha caused by the introduction of
      E2F2. CONCLUSIONS: This study confirms the pathological role of E2F2 in RA and
      found that the E2F2-STAT1/MyD88-Akt axis is closely related with the inflammatory
      phenotype in RASFs.

PMID- 30286794
TI  - Cell-gel interactions of in-gel propagating bacteria.
AB  - OBJECTIVE: Our immediate objective is to test the data-suggested possibility that
      in-agarose gel bacterial propagation causes gel fiber dislocation and alteration
      of cell distribution. We also test the further effect of lowering water activity.
      We perform these tests with both Gram-negative and Gram-positive bacteria. Data
      are obtained via electron microscopy of thin sections, which provides the first
      images of both bacteria and gel fibers in gel-supported bacterial lawns. The long
      term objective is analysis of the effects of in-gel propagation on the DNA
      packaging of phages. RESULTS: We find that agarose gel-supported cells in lawns
      of Escherichia coli and Lysinibacillus (1) are primarily in clusters that
      increase in size with time and are surrounded by gel fibers, and (2) sometimes
      undergo gel-induced, post-duplication rotation and translation. Bacterial growth
      induced dislocation of gel fibers is observed. One reason for clustering is that
      clustering promotes growth by increasing the growth-derived force applied to the
      gel fibers. Reactive force exerted by gel on cells explains cell movement.
      Finally, addition to growth medium of 0.94 M sucrose causes cluster-associated E.
      coli cells to become more densely packed and polymorphic. Shape is determined, in
      part, by neighboring cells, a novel observation to our knowledge.

PMID- 30286796
TI  - Iceberg of workplace violence in health sector of Bangladesh.
AB  - OBJECTIVES: 'Negligence of Physicians' and 'Wrong Treatment' have become commonly
      used phrases in print and electronic media of Bangladesh, while violence against
      healthcare workers has always been under-reported. Unfortunately, there is little
      evidence regarding physical violence against healthcare workers, while there is
      no data on the magnitude of psychological violence. The objective of this study
      was to quantify and explore the magnitude of workplace violence in health sector
      of Bangladesh to guide future research and adopt preventive policies. RESULTS:
      The Majority (96%, n = 54) of the violence cases were physical in nature and 91%
      violence (n = 51) took place in public healthcare settings. More than one-third
      (39%) of the violence cases occurred at primary healthcare level and one-third
      (39%) at tertiary healthcare level. It was mostly (61%) the entry-level
      physicians who were affected by violence. The report reveals the tip of the
      iceberg of workplace violence in health sector of Bangladesh. Further studies
      should be undertaken to assess the prevalence, magnitude, and associated factors
      for workplace violence against healthcare workers.

PMID- 30286795
TI  - The methylome of the marbled crayfish links gene body methylation to stable
      expression of poorly accessible genes.
AB  - BACKGROUND: The parthenogenetic marbled crayfish (Procambarus virginalis) is a
      novel species that has rapidly invaded and colonized various different habitats.
      Adaptation to different environments appears to be independent of the selection
      of genetic variants, but epigenetic programming of the marbled crayfish genome
      remains to be understood. RESULTS: Here, we provide a comprehensive analysis of
      DNA methylation in marbled crayfish. Whole-genome bisulfite sequencing of
      multiple replicates and different tissues revealed a methylation pattern that is
      characterized by gene body methylation of housekeeping genes. Interestingly, this
      pattern was largely tissue invariant, suggesting a function that is unrelated to
      cell fate specification. Indeed, integrative analysis of DNA methylation,
      chromatin accessibility and mRNA expression patterns revealed that gene body
      methylation correlated with limited chromatin accessibility and stable gene
      expression, while low-methylated genes often resided in chromatin with higher
      accessibility and showed increased expression variation. Interestingly, marbled
      crayfish also showed reduced gene body methylation and higher gene expression
      variability when compared with their noninvasive mother species, Procambarus
      fallax. CONCLUSIONS: Our results provide novel insights into invertebrate gene
      body methylation and its potential role in adaptive gene regulation.

PMID- 30286797
TI  - Physical Activity after Cardiac EventS (PACES) - a group education programme with
      subsequent text-message support designed to increase physical activity in
      individuals with diagnosed coronary heart disease: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Coronary heart disease (CHD) represents approximately 13% of deaths
      worldwide and is the leading cause of death in the UK with considerable
      associated health care costs. After a CHD event, timely cardiac rehabilitation
      optimises patient outcomes. However, a high percentage of these services do not
      meet necessary performance indicators such as course length and follow-up
      attendance. Uptake of such services is only 50% in UK patients and support
      provided 12 months after an event is often limited. To delay and prevent further
      CHD events leading to hospitalisation, supplementary self-management strategies
      such as group education, are necessary. METHODS: This is a single-centre,
      randomised controlled trial (RCT) recruiting participants (n = 290) aged >=18
      years who are 12 to 48 months post diagnosis of a CHD-related cardiac event
      (myocardial infarction, angina and any other acute coronary syndrome). The study
      aims to implement a structured education programme, with text-message support
      over 12 months, and identify whether delivery of the programme, to individuals
      who have a history of a cardiac event, would be an effective and cost-effective
      strategy for increasing walking. The primary outcome, objectively measured
      average daily physical activity, specifically step count through walking
      activity, is assessed using the wrist-worn GENEActiv accelerometer at baseline, 6
      and 12 months. Secondary outcomes at 12 months include cardiovascular risk
      factors such as smoking status, blood pressure, lipid profile, glycated
      haemoglobin (HbA1c), obesity, self-efficacy, quality of life, physical activity
      and physical function. Participants are randomised to either the control group
      receiving standard care and a physical activity information leaflet, or the
      intervention group whose partcipants receive the leaflet and are invited to
      attend two group-based structured education sessions. These encourage
      participants to adopt and maintain healthy behaviours and self-manage their
      lifestyle. They are delivered approximately 2 weeks apart by trained facilitators
      and reinforced via subsequent text-message support. DISCUSSION: To our knowledge,
      this is the first trial designed to assess the effectiveness of a group education
      programme 12 to 48 months after a CHD event diagnosis. If successful, the PACES
      programme could be translated into effective post-operative cardiac care and
      complement the current post-operative services available. TRIAL REGISTRATION:
      ISRCTN, ID: ISRCTN91163727 . The trial was registered on 27 February 2017.

PMID- 30286798
TI  - Optimizing huddle engagement through leadership and problem-solving within
      primary care: A study protocol for a cluster randomized trial.
AB  - BACKGROUND: Team-based care has been identified as a key component in
      transforming primary care. An important factor in implementing team-based care is
      the requirement for teams to have daily huddles. During huddles, the care team,
      comprising physicians, nurses, and administrative staff, come together to discuss
      their daily schedules, track problems, and develop countermeasures to fix these
      problems. However, the impact of these huddles on staff burnout over time and
      patient outcomes are not clear. Further, there are challenges to implementing
      huddles in fast-paced primary care clinics. We will test whether the impact of a
      behavioral intervention of leadership training and problem-solving during the
      daily huddling process will result in higher consistent huddling in the
      intervention arm and result in higher team morale, reduced burnout, and improved
      patient outcomes. METHODS/DESIGN: We will conduct a care-team-level cluster
      randomized trial within primary care practices in two Midwestern states. The
      intervention will comprise a 1-day training retreat for leaders of primary care
      teams, biweekly sessions between huddle optimization coaches and members of the
      primary care teams, as well as coaching site visits at 30 and 100 days post
      intervention. This behavioral intervention will be compared to standard care, in
      which care teams have huddles without any support or training. Surveys of primary
      care team members will be administered at baseline (prior to training), 100 days
      (for the intervention arm only), and 180 days to assess team dynamics. The
      primary outcome of this trial will be team morale. Secondary outcomes will assess
      the impact of this intervention on clinician burnout, patient satisfaction, and
      quality of care. DISCUSSION: This trial will provide evidence on the impact of a
      behavioral intervention to implement huddles as a key component of team-based
      care models. Knowledge gained from this trial will be critical to broader
      deployment and successful implementation of team-based care models. TRIAL
      REGISTRATION: Clinicaltrials.gov , NCT03062670 . Registered on 23 February 2017.

PMID- 30286799
TI  - The frequency of ANCA-associated vasculitis in a national database of
      hospitalized patients in China.
AB  - BACKGROUND: Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis
      (AAV) is a group of life-threatening autoimmune diseases. The epidemiological
      data on AAV in China are limited. The aim of the present study is to investigate
      the frequency, geographical distribution, and ethnic distribution of AAV in
      hospitalized patients in China, and its association with environmental pollution.
      METHODS: We investigated the hospitalized patients in a national inpatient
      database covering 54.1% tertiary hospitals in China from 2010 to 2015. Diagnosis
      of AAV was extracted according to the definition of International Classification
      of Diseases (ICD)-10 codes and free text. Variables from the front page of
      inpatient records were collected and analyzed, including frequency, geographic
      distribution, demographic characteristics and seasonal variations of AAV. The
      association between various environmental pollutants and frequency of AAV was
      further analyzed. RESULTS: Among 43.7 million inpatients included in the study
      period, 0.250/00 (10,943) were diagnosed as having AAV. The frequency of AAV was
      relatively stable during the study period (from 0.340/00 in 2010 to 0.270/00 in
      2015). The proportion of AAV increased with latitude (0.440/00 in Northern China
      and 0.270/00 in Southern China in 2015). Hospitalizations were mostly observed in
      winter (30.2%). The Dong population, an ethnic minority of the Chinese
      population, had the highest frequency of patients with AAV (0.670/00). We also
      found a positive association between the exposure to carbon monoxide and the
      frequency of AAV (R2 = 0.172, p = 0.025). In Yunnan province, the frequency of
      AAV increased 1.37-fold after the Zhaotong earthquake, which took place in 2014.
      CONCLUSIONS: Our present investigation of hospitalized patients provided
      epidemiological information on AAV in China for the first time. A spatial and
      ethnic clustering trend and an association between pollution and the frequency of
      AAV were observed.

PMID- 30286801
TI  - Time to death and risk factors among tuberculosis patients in Northern Ethiopia.
AB  - OBJECTIVE: The main objective of this study was to assess time to death and
      associated risk factors among tuberculosis (TB) patients. RESULTS: A total of 769
      TB patients were studied and of those, 87 (11.3%) patients died. All of the
      deaths occurred within 7 months of anti-tuberculosis therapy. Extra-pulmonary TB
      (AHR = 17.376, 95% CI; 3.88-77.86, p < 0.001) as compared to pulmonary TB and
      cotrimoxazole prophylaxis therapy (CPT) (AHR = 0.15, 95% CI; 0.03-0.74, p = 0.02)
      were found to be the predictors of mortality. We noticed higher rates of
      mortality. Extra-pulmonary TB patients have high risk and TB-HIV co-infected
      patients who received CPT have low risk of death. Improving early diagnosis of
      extra-pulmonary TB and early CPT initiation of TB-HIV co-infected patients could
      minimize patient's mortality.

PMID- 30286800
TI  - A new blood parasite of leaf warblers: molecular characterization, phylogenetic
      relationships, description and identification of vectors.
AB  - BACKGROUND: Blood parasites of the genus Haemoproteus Kruse, 1890 are
      cosmopolitan, might be responsible for mortality in non-adapted birds, and often
      kill blood-sucking insects. However, this group remains insufficiently
      investigated in the wild. This is particularly true for the parasites of leaf
      warblers of the Phylloscopidae Alstrom, Ericson, Olsson & Sundberg the common
      small Old World passerine birds whose haemoproteid parasite diversity and vectors
      remain poorly studied. This study reports a new species of Haemoproteus
      parasitizing leaf warblers, its susceptible vector and peculiar phylogenetic
      relationships with other haemoproteids. METHODS: Wood warblers (Phylloscopus
      sibilatrix Bechstein) were caught in Lithuania during spring migration, and blood
      films were examined microscopically. Laboratory reared Culicoides nubeculosus
      Meigen were exposed experimentally by allowing them to take blood meals on one
      individual harbouring mature gametocytes of the new Haemoproteus species (lineage
      hPHSIB2). To follow sporogonic development, the engorged insects were dissected
      at intervals. The parasite lineage was distinguished using sequence data, and
      morphological analysis of blood and sporogonic stages was carried out. Bayesian
      phylogeny was constructed in order to determine the phylogenetic relationships of
      the new parasite with other haemoproteids. RESULTS: Haemoproteus
      (Parahaemoproteus) homopalloris n. sp. was common in wood warblers sampled after
      arrival to Europe from their wintering grounds in Africa. The new parasite
      belongs to a group of avian haemoproteid species with macrogametocytes possessing
      pale staining cytoplasm. All species of this group clustered together in the
      phylogenetic analysis, indicating that intensity of the cytoplasm staining is a
      valuable phylogenetic character. Laboratory-reared biting midges C. nubeculosus
      readily supported sporogony of new infections. Phylogenetic analysis corroborated
      vector experiments, placing the new parasite in the clade of Haemoproteus
      (Parahaemoproteus) parasites transmitted by biting midges. CONCLUSIONS:
      Haemoproteus homopalloris n. sp. is the third haemoproteid, which is described
      from and is prevalent in wood warblers. Phylogenetic analysis identified a clade
      containing seven haemoproteids, which are characterised by pale staining of the
      macrogametocyte cytoplasm and with ookinetes maturing exceptionally rapidly
      (between 1 to 1.5 h after exposure to air). Both these features may represent
      valuable phylogenetic characters. Studies targeting mechanisms of sporogonic
      development of haemoproteids remain uncommon and should be encouraged. Culicoides
      nubeculosus is an excellent experimental vector of the new parasite species.

PMID- 30286804
TI  - A robust cell culture system for large scale feeder cell-free expansion of human
      breast epithelial progenitors.
AB  - BACKGROUND: Normal human breast epithelial cells are maintained by the
      proliferation and differentiation of different human breast epithelial
      progenitors (HBEPs). However, these progenitor subsets can only be obtained at
      low frequencies, limiting their further characterization. Recently, it was
      reported that HBEPs can be minimally expanded in Matrigel cocultures with stromal
      feeder cells. However, variability of generating healthy feeder cells
      significantly impacts the effective expansion of HBEPs. METHODS: Here, we report
      a robust feeder cell-free culture system for large-scale expansion of HBEPs in
      two-dimensional cultures. RESULTS: Using this cell culture system HBEPs can be
      exponentially expanded as bulk cultures. Moreover, purified HBEP subtypes can
      also be separately expanded using our cell culture system. The expanded HBEPs
      retain their undifferentiated phenotype and form distinct epithelial colonies in
      colony forming cell assays. CONCLUSIONS: The availability of a culture system
      enabling the large-scale expansion of HBEPs facilitates their application to
      screening platforms and other cell-based assays.

PMID- 30286803
TI  - SKESA: strategic k-mer extension for scrupulous assemblies.
AB  - SKESA is a DeBruijn graph-based de-novo assembler designed for assembling reads
      of microbial genomes sequenced using Illumina. Comparison with SPAdes and MegaHit
      shows that SKESA produces assemblies that have high sequence quality and
      contiguity, handles low-level contamination in reads, is fast, and produces an
      identical assembly for the same input when assembled multiple times with the same
      or different compute resources. SKESA has been used for assembling over 272,000
      read sets in the Sequence Read Archive at NCBI and for real-time pathogen
      detection. Source code for SKESA is freely available at
      https://github.com/ncbi/SKESA/releases .

PMID- 30286802
TI  - Multiple paralogues of alpha-SNAP in Giardia lamblia exhibit independent
      subcellular localization and redistribution during encystation and stress.
AB  - BACKGROUND: The differently-diverged parasitic protist Giardia lamblia is known
      to have minimal machinery for vesicular transport. Yet, it has three paralogues
      of SNAP, a crucial component that together with NSF brings about disassembly of
      the cis-SNARE complex formed following vesicle fusion to target membranes. Given
      that most opisthokont hosts of this gut parasite express only one alpha-SNAP,
      this study was undertaken to determine whether these giardial SNAP proteins have
      undergone functional divergence. RESULTS: All three SNAP paralogues are expressed
      in trophozoites, encysting trophozoites and cysts. Even though one of them
      clusters with gamma-SNAP sequences in a phylogenetic tree, functional
      complementation analysis in yeast indicates that all the three proteins are
      functionally orthologous to alpha-SNAP. Localization studies showed a mostly non
      overlapping distribution of these alpha-SNAPs in trophozoites, encysting cells
      and cysts. In addition, two of the paralogues exhibit substantial subcellular
      redistribution during encystation, which was also seen following exposure to
      oxidative stress. However, the expression of the three genes remained unchanged
      during this redistribution process. There is also a difference in the affinity of
      each of these alpha-SNAP paralogues for GlNSF. CONCLUSIONS: None of the genes
      encoding the three alpha-SNAPs are pseudogenes and the encoded proteins are
      likely to discharge non-redundant functions in the different morphological states
      of G. lamblia. Based on the difference in the interaction of individual alpha
      SNAPs with GlNSF and their non-overlapping pattern of subcellular redistribution
      during encystation and under stress conditions, it may be concluded that the
      three giardial alpha-SNAP paralogues have undergone functional divergence.
      Presence of one of the giardial alpha-SNAPs at the PDRs of flagella, where
      neither GlNSF nor any of the SNAREs localize, indicates that this alpha-SNAP
      discharges a SNARE-independent role in this gut pathogen.

PMID- 30286805
TI  - Burkitt lymphoma of the ovaries mimicking sepsis: a case report and review of the
      literature.
AB  - BACKGROUND: It is not unusual for systemic diseases to mimic sepsis and, in any
      case, the clinician should thoroughly investigate this possibility. CASE
      PRESENTATION: We present the case of a 21-year-old Greek woman who presented to
      the Intensive Care Unit of our hospital with severe septic shock - multiple organ
      failure as a result of a suspected gynecological infection of the ovaries. An
      immediate improvement of her clinical condition in combination with strong
      clinical suspicion and negative cultures led to the differential diagnosis of
      diseases other than sepsis. Based on the results of the biopsies that were
      obtained by research laparotomy, our patient suffered from primary Burkitt
      ovarian lymphoma. Her clinical condition improved with supportive treatment and
      chemotherapy. Chemotherapy is the dominant treatment for Burkitt's lymphoma,
      while surgery or radiotherapy has no place. CONCLUSIONS: All intensivists should
      be aware of clinical conditions that mimic sepsis as early diagnosis can lead to
      appropriate therapy and avoid unnecessary diagnostic tests and antibiotic abuse.

PMID- 30286806
TI  - Inverse association between estrogen receptor-alpha DNA methylation and breast
      composition in adolescent Chilean girls.
AB  - BACKGROUND: Estrogen receptor-alpha (ER-alpha) is a transcriptional regulator,
      which mediates estrogen-dependent breast development, as well as breast
      tumorigenesis. The influence of epigenetic regulation of ER-alpha on adolescent
      breast composition has not been previously studied and could serve as a marker of
      pubertal health and susceptibility to breast cancer. We investigated the
      association between ER-alpha DNA methylation in leukocytes and breast composition
      in adolescent Chilean girls enrolled in the Growth and Obesity Cohort Study
      (GOCS) in Santiago, Chile. Breast composition (total breast volume (BV; cm3),
      fibroglandular volume (FGV; cm3), and percent fibroglandular volume (%FGV)) was
      measured at breast Tanner stage 4 (B4). ER-alpha promoter DNA methylation was
      assessed by pyrosequencing in blood samples collected at breast Tanner stages 2
      (B2; n = 256) and B4 (n = 338). RESULTS: After adjusting for fat percentage at
      breast density measurement, ER-alpha methylation at B2, and cellular
      heterogeneity, we observed an inverse association between B4 average ER-alpha DNA
      methylation and BV and FGV. Geometric mean BV was 15% lower (95% CI: - 28%, - 1%)
      among girls in the highest quartile of B4 ER-alpha methylation (6.96-23.60%)
      relative to the lowest (0.78-3.37%). Similarly, FGV was 19% lower (95% CI: - 33%,
      - 2%) among girls in the highest quartile of B4 ER-alpha methylation relative to
      the lowest. The association between ER-alpha methylation and breast composition
      was not significantly modified by body fat percentage and was not influenced by
      pubertal timing. CONCLUSIONS: These findings suggest that the methylation profile
      of ER-alpha may modulate adolescent response to estrogen and breast composition,
      which may influence breast cancer risk in adulthood.

PMID- 30286808
TI  - The therapeutic potential of bone marrow mesenchymal stem cells in premature
      ovarian failure.
AB  - With the development of regenerative medicine, a variety of mesenchymal stem
      cells (MSCs) are increasingly considered for the treatment of premature ovarian
      failure (POF). Reportedly, bone marrow-derived MSCs (BMSCs) improve the ovarian
      reserve, which mainly depends on homing and paracrine activities. Furthermore,
      paracrine factors secreted by these stem cells play an important role in ovarian
      recovery. Relevant studies indicate that BMSC transplantation has some positive
      effects on the treatment of POF in animals, but BMSCs are not widely applied in
      clinical therapy. Clinical trials are ongoing despite the fact that several
      patients experiencing BMSC transplantation recover their normal menstrual cycles
      and even give birth to babies. In this review, we discuss the possible
      therapeutic mechanisms of BMSCs for POF, migration, antiapoptosis, antifibrosis,
      angiogenesis, anti-inflammation, immunoregulation, and oxidative stress, which
      provide the theoretical basis for further study and clinical therapy.

PMID- 30286807
TI  - Pediatric asthma comprises different phenotypic clusters with unique nasal
      microbiotas.
AB  - BACKGROUND: Pediatric asthma is the most common chronic childhood disease in the
      USA, currently affecting ~ 7 million children. This heterogeneous syndrome is
      thought to encompass various disease phenotypes of clinically observable
      characteristics, which can be statistically identified by applying clustering
      approaches to patient clinical information. Extensive evidence has shown that the
      airway microbiome impacts both clinical heterogeneity and pathogenesis in
      pediatric asthma. Yet, so far, airway microbiotas have been consistently
      neglected in the study of asthma phenotypes. Here, we couple extensive clinical
      information with 16S rRNA high-throughput sequencing to characterize the
      microbiota of the nasal cavity in 163 children and adolescents clustered into
      different asthma phenotypes. RESULTS: Our clustering analyses identified three
      statistically distinct phenotypes of pediatric asthma. Four core OTUs of the
      pathogenic genera Moraxella, Staphylococcus, Streptococcus, and Haemophilus were
      present in at least 95% of the studied nasal microbiotas. Phyla (Proteobacteria,
      Actinobacteria, and Bacteroidetes) and genera (Moraxella, Corynebacterium,
      Dolosigranulum, and Prevotella) abundances, community composition, and structure
      varied significantly (0.05 < P <= 0.0001) across asthma phenotypes and one of the
      clinical variables (preterm birth). Similarly, microbial networks of co
      occurrence of bacterial genera revealed different bacterial associations across
      asthma phenotypes. CONCLUSIONS: This study shows that children and adolescents
      with different clinical characteristics of asthma also show different nasal
      bacterial profiles, which is indicative of different phenotypes of the disease.
      Our work also shows how clinical and microbial information could be integrated to
      validate and refine asthma classification systems and develop biomarkers of
      disease.

PMID- 30286810
TI  - Identification of gross deletions in FBN1 gene by MLPA.
AB  - BACKGROUND: Marfan syndrome (MFS) is an autosomal dominant connective tissue
      disorder caused by mutations in the FBN1 gene. Approximately 90% of classic MFS
      patients have a FBN1 mutation that can be identified by single-gene sequencing or
      gene-panel sequencing targeting FBN1. However, a small proportion of MFS patients
      carry a large genomic deletion in FBN1, which cannot be detected by routine
      sequencing. Here, we performed an MLPA (multiplex ligation-dependent probe
      amplification) test to detect large deletions and/or duplications in FBN1 and
      TGFBR2 in 115 unrelated Chinese patients with suspected MFS or early-onset
      aneurysm/dissection. RESULTS: Five novel large deletions encompassing a single
      exon or multiple exons in the FBN1 gene were characterized in five unrelated
      patients, of which four were proven by Sanger sequencing, and the breakpoints
      were identified. Three of them met the revised Ghent criteria when genetic
      results were not available, and the other two patients were highly suspected and
      diagnosed with MFS until the FBN1 deletions were identified. CONCLUSIONS: Our
      finding expands the mutation spectrum of large FBN1 deletions and emphasizes the
      importance of screening for large FBN1 deletions in clinical genetic testing,
      especially for those with classic Marfan phenotype.

PMID- 30286809
TI  - Therapeutic and immunoregulatory effects of water-soluble alkaloids E2-a from
      Sophora moorcroftiana seeds as a novel potential agent against echinococcosis in
      experimentally protoscolex-infected mice.
AB  - Novel compounds and more efficient treatment options are urgently needed for the
      treatment of cystic echinococcosis (CE), which is caused by Echinococcus
      granulosus. The decoction of Sophora moorcroftiana (Fabaceae) has been used to
      treat parasitosis for years in traditional Tibetan medicine. The aim of this
      study was to screen insecticidal water-soluble alkaloids from S. moorcroftiana
      seeds and evaluate the therapeutic effects against CE and the immune response
      induced by the alkaloidal fraction. Low polarity compounds (E2-a) were isolated
      from water-soluble alkaloid (E2) and matrine and sophocarpine were identified as
      major components. The E2-a fraction was more effective against protoscoleces than
      other constituents from S. moorcroftiana. After 20 weeks of secondary infection
      with protoscoleces, mice were orally treated with E2-a (100 mg/kg/day) for 6
      weeks to evaluate therapeutic and immunoregulatory activities. Compared with the
      untreated group, E2-a treatment induced a significant reduction in cyst weight
      (mean 2.93 g) (p < 0.05) and an impaired ultrastructural modification of the
      cyst. Interestingly, the application of E2-a resulted in a significant increased
      frequency of CD3+CD4+ T-cell subsets and decreased frequency of CD3+PD-1+ T-cell
      subsets, compared with protoscolece-infected mice without treatment. The E2-a
      fraction of S. moorcroftiana can inhibit the cyst development of CE and boost the
      specific immune response by reducing the expression of PD-1 and accelerate the
      cytokine secretion of antigen-specific T-cells. All data suggest the E2-a
      fraction from S. moorcroftiana seeds may be used as a new potential therapeutic
      option against E. granulosus infection.

PMID- 30286812
TI  - The role of saline irrigation prior to wound closure in the reduction of surgical
      site infection: protocol for a systematic review and meta-analysis.
AB  - BACKGROUND: Surgical site infection describes an infectious complication of
      surgical wounds. This single complication is thought to occur in close to 20% of
      surgical cases. This complication has been described in all kinds of surgical
      procedure including minimally invasive procedures. Wound irrigation is frequently
      used as a means of reducing surgical site infection. However, there is lack of
      solid evidence to support routine wound irrigation. The aim of this review is to
      provide evidence for the efficacy of routine wound irrigation with normal saline
      in preventing surgical site infection. The rate of surgical site infection in
      cases with and without wound irrigation will be analyzed. METHODS/DESIGN:
      Systematic literature searches will be conducted to identify all published and
      unpublished studies. The following databases will be searched for citations from
      inception to present: MEDLINE (via PubMed), Embase (via Embase), and CENTRAL (via
      the Cochrane library). The search strategy will be developed by the research team
      in collaboration with an experienced librarian and checked by a referee according
      to the Peer Review of Electronic Search Strategies (PRESS) guideline. A draft of
      the PubMed search strategy could be (irrigation[tiab] OR "Therapeutic
      Irrigation"[mesh] OR lavage[tiab]) AND (saline[tiab] OR "Sodium Chloride"[mesh]
      OR sodium chloride[tiab]) NOT ("Comment" [Publication Type] OR "Letter"
      [Publication Type] OR "Editorial" [Publication Type]). No time limits will be
      set. The reference lists of eligible articles will be hand searched. Relevant
      data will be extracted from eligible studies using a previously designed data
      extraction sheet. Relative risks will be calculated for binary outcomes and mean
      differences or standardized mean differences, if necessary, for continuous
      outcomes. For all measures, 95% confidence levels will be calculated. Both arms
      would be compared with regard to the rate of surgical site infection within 30
      days following surgery. We will report the review using the Preferred Reporting
      Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. DISCUSSION:
      This review aims at investigating the value of routine wound irrigation using
      normal saline in preventing surgical site infection. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO: CRD42018082287.

PMID- 30286814
TI  - Time-varying associations of racial discrimination and adjustment among Chinese
      heritage adolescents in the United States and Canada.
AB  - The aim of our study was twofold: to examine (a) whether the link between racial
      discrimination and adjustment showed age-related changes across early to late
      adolescence for Chinese-heritage youth and (b) whether the age-related
      associations of the discrimination-adjustment link differed by gender, nativity,
      and geographical region. We pooled two independently collected longitudinal data
      sets in the United States and Canada (N = 498, ages 12-19 at Wave 1) and used
      time-varying effect modeling to show that discrimination is consistently
      associated with poorer adjustment across all ages. These associations were
      stronger at certain ages, but for males and females, first- and second-generation
      adolescents, and US and Canadian adolescents they differed. There were stronger
      relations between discrimination and adjustment in early adolescence for males
      compared to females, in middle adolescence for first-generation compared to
      second-generation adolescents, and in early adolescence for US adolescents
      compared to Canadian adolescents. In general, negative implications for
      adjustment associated with discrimination diminished across the span of
      adolescence for females, second-generation, and US and Canadian adolescents, but
      not for males or first-generation adolescents. The results show that the
      discrimination-adjustment link must be considered with regard to age, gender,
      nativity, and region, and that attention to discrimination in early adolescence
      may be especially important.

PMID- 30286815
TI  - Field Evaluation of a Novel UV Water Disinfection System for use in Underserved
      Rural Communities.
AB  - Reliable, robust, and inexpensive disinfection systems are needed to expand water
      security in remote and underserviced areas. This paper reports on the deployment
      and evaluation of a novel UV water-disinfection system in a remote rural
      community. Prior laboratory tests indicated a 7.12 log10 reduction of the
      bacteriophage MS-2 at a flow rate of 9.46 liter/min, which corresponds to a
      supplied UV dose 215 mJ/cm2. Further tests in water containing turbidity levels
      up to 18 NTU showed E. coli removal remaining above the 5 log10 level. Field
      testing was performed at a Native American reservation in Northern California
      where the system was used to treat groundwater obtained from a well with a known
      fecal contamination. The system was powered by solar panel and was operated on
      demand for extended periods. Tests on the treated water showed that the system
      exceeded the standard of disinfection required for drinking water.

PMID- 30286813
TI  - Inhibition of Salmonella Typhimurium adhesion, invasion, and intracellular
      survival via treatment with methyl gallate alone and in combination with
      marbofloxacin.
AB  - Salmonella enterica serovar Typhimurium infects intestinal epithelia and
      macrophages, which is prevented by inhibiting adhesion and cell invasion. This
      study aimed to investigate the role of methyl gallate (MG) in adhesion, invasion,
      and intracellular survival of Salmonella Typhimurium in Caco-2 and RAW 264.7
      cells via a gentamicin protection assay, confocal microscopy, and quantitative
      reverse-transcription polymerase chain reaction. MG (30 ug/mL) inhibited adhesion
      and invasion of Salmonella Typhimurium by 54.01% and 60.5% in RAW 264.7 cells,
      respectively. The combination of MG with sub-minimum inhibitory concentration
      (MIC) of marbofloxacin (MRB) inhibited the adhesion, invasion, and intracellular
      survival by 70.49%, 67.36%, and 74%, respectively. Confocal microscopy further
      revealed reductions in bacterial count in Caco-2 cells treated with MG alone or
      with sub-MIC of MRB. Furthermore, MG alone or in combination with sub-MIC of MRB
      decreased the motility of Salmonella Typhimurium. Quorum sensing genes including
      sdiA, srgE, and rck were downregulated by 52.8%, 61.7%, and 22.2%, respectively.
      Moreover, rac-1 was downregulated by 56.9% and 71.9% for MG alone and combined
      with sub-MIC of MRB, respectively, in mammalian cells. Furthermore, MG
      downregulated virulence genes of Salmonella Typhimurium including cheY, ompD,
      sipB, lexA, and ompF by 59.6%, 60.2%, 20.5%, 31.4%, and 16.2%, respectively.
      Together, the present results indicate that MG alone or in combination with a sub
      MIC of MRB effectively inhibited the adhesion, invasion, and intracellular
      survival of Salmonella Typhimurium in vitro by downregulating quorum sensing and
      virulence genes.

PMID- 30286811
TI  - Chinese expert consensus on echelons treatment of thoracic injury in modern
      warfare.
AB  - The emergency treatment of thoracic injuries varies of general conditions and
      modern warfare. However, there are no unified battlefield treatment guidelines
      for thoracic injuries in the Chinese People's Liberation Army (PLA). An expert
      consensus has been reached based on the epidemiology of thoracic injuries and the
      concept of battlefield treatment combined with the existing levels of military
      medical care in modern warfare. Since there are no differences in the specialized
      treatment for thoracic injuries between general conditions and modern warfare,
      first aid, emergency treatment, and early treatment of thoracic injuries are
      introduced separately in three levels in this consensus. At Level I facilities,
      tension pneumothorax and open pneumothorax are recommended for initial assessment
      during the first aid stage. Re-evaluation and further treatment for hemothorax,
      flail chest, and pericardial tamponade are recommended at Level II facilities. At
      Level III facilities, simple surgical operations such as emergency thoracotomy
      and debridement surgery for open pneumothorax are recommended. The grading
      standard for evidence evaluation and recommendation was used to reach this expert
      consensus.

PMID- 30286816
TI  - A Missed Connection: Dietary Protein Intake and Mortality in Hemodialysis.

PMID- 30286817
TI  - Women's Health in Inflammatory Bowel Disease.
AB  - About half of all inflammatory bowel disease (IBD) patients are women. It is
      important that physicians are aware of gender-specific needs women with IBD may
      have. This review covers general and specific women's health issues related to
      their IBD. It is intended to be practical and give a brief overview of topics
      including body image, menstruation, contraception, cervical cancer screening,
      preconception counseling, anxiety, depression, pregnancy, breastfeeding,
      menopause, skin exams, vaccines, laboratory monitoring and bone health.

PMID- 30286818
TI  - Is Dietary Protein Intake Predictive of 1-Year Mortality in Dialysis Patients?
AB  - BACKGROUND: High mortality in dialysis patients may be associated with protein
      energy wasting (PEW) syndrome characterized by progressively depleted protein and
      energy stores. While early diagnosis and treatment of PEW can reduce mortality,
      clinically practical measures for its detection are lacking. Poor dietary protein
      intake (DPI) is associated with risk of malnutrition and PEW. However, the impact
      of DPI on mortality is unclear. The purpose of this study is to examine the
      ability of DPI to predict 1-year mortality in dialysis patients. METHODS: This
      prospective, secondary study using data from the Comprehensive Dialysis Study and
      United States Renal Data System examined risk factors associated with 1-year
      mortality in dialysis patients. RESULTS: Seventeen (7.5%) of the 227 subjects
      died within 1 year following baseline data collection. One year survivors were
      significantly younger (60 +/- 13.6 versus 71 +/- 12.8; P = 0.0043), had a lower
      Charlson Comorbidity Index score (1.6 +/- 2.3 versus 4.0 +/- 3.6; P = 0.0157),
      higher serum albumin level (3.5 +/- 0.5 versus 3.3 +/- 0.4; P = 0.0173) and had
      higher DPI (63 +/- 33.7 versus 49.5 +/- 21.5 g/day; P = 0.0386) than those who
      died. In multivariable Cox proportional hazards model analyses, only the Charlson
      Comorbidity Index adjusted hazard ratio for death (1.24) was significantly
      associated with increased mortality. The Comprehensive Dialysis Study data showed
      no association between DPI and 1-year mortality in dialysis patients.
      CONCLUSIONS: Future studies using more precise measures should further examine
      the impact of DPI on mortality given the known association of DPI with PEW
      syndrome and the definitive link between PEW syndrome and survival in dialysis
      patients.

PMID- 30286819
TI  - Cardiovascular Parameters Associated With Troponin I as Indicators for 14-Day
      Mortality in Patients With Septic Shock.
AB  - BACKGROUND: Troponin I is better than other troponin isoforms for monitoring
      cardiocyte damage, and correlates with sepsis-related mortality. However,
      hemodynamic factors possibly interact with cardiac function to affect mortality
      in sepsis. Thus, this study used parameters from pulse-induced contour cardiac
      output (PiCCO) to investigate the possibility. METHODS: Patients with troponin I
      tests and sequential organ failure assessment score >=2 were selected and divided
      into survivors and nonsurvivors groups and blood troponin I levels between them
      were compared. Additionally, 65 patients with septic shock and PiCCO records were
      selected and divided into high cardiac function index (CFI) and low CFI groups
      and their cardiac function associated with troponin I levels was checked.
      Furthermore, the patients were classified into 4 subgroups based on CFI and
      another hemodynamical parameter of PiCCO for identifying if any interaction
      between CFI and the parameter existed. RESULTS: High blood troponin I levels
      correlated with high mortality, and with low cardiac function (CFI < 4.5) alone
      or with low CFI combined with high stroke volume variation (SVV), but did not
      correlate with global end-diastolic index (GEDI), or systemic vascular resistance
      index. However, only the subgroup with low CFI and high SVV (CFI < 4.5 and SVV >
      10) increased mortality. CONCLUSIONS: Our data give an insight into interactions
      between cardiac and hemodynamic factors to cause cardiocyte damage and suggest
      that multiple factors (i.e., low CFI and high SVV) should be considered together
      to evaluate cardiocyte damage and mortality in sepsis.

PMID- 30286820
TI  - Efficacy and Safety of Policosanol Plus Fenofibrate Combination Therapy in
      Elderly Patients with Mixed Dyslipidemia: A Randomized, Controlled Clinical
      Study.
AB  - BACKGROUND: Policosanol is a mixture of long-chain alcohols isolated from sugar
      cane. This controlled, randomized clinical trial was designed to compare the
      efficacy and safety of fenofibrate, policosanol and a combination of these 2 in
      lowering low-density-lipoprotein cholesterol (LDL-C) in elderly patients with
      mixed dyslipidemia. METHODS: A total of 102 patients aged >=60years were randomly
      assigned into 3 groups: patients receiving a 24-week therapy of fenofibrate (200
      mg/day), policosanol (20 mg/day) or fenofibrate + policosanol combination. Lipids
      were evaluated at baseline, after 16 and after 24 weeks of therapy. Brachial
      ankle pulse wave velocity (ba-PWV) was performed, and SF-36 questionnaires were
      used to evaluate the patients' quality of life. The primary endpoint was the
      percentage reduction in LDL-C. The secondary end points included percentage
      change in nonhigh density lipoprotein cholesterol (non-HDL-C), total cholesterol
      (TC), triglyceride, high-density-lipoprotein cholesterol (HDL-C), ba-PWV and SF
      36 scores. Safety was assessed by adverse events and laboratory parameters.
      RESULTS: LDL-C, non-HDL-C and TC were decreased, respectively after treatment
      with policosanol for 24 weeks (P < 0.01). Treatment with policosanol +
      fenofibrate resulted in significantly greater reductions in TC, non-HDL-C and LDL
      C compared to fenofibrate alone (P < 0.01, respectively). There were significant
      increases in SF-36 scores in the policosanol and policosanol + fenofibrate groups
      (P < 0.05), and significant improvements of ba-PWV in the 2 groups (P < 0.01).
      There were no serious adverse events or significant changes in laboratory
      variables after any of the treatment regimens. CONCLUSIONS: Policosanol +
      fenofibrate combination therapy significantly improved lipid parameters, arterial
      stiffness, and quality of life, with good tolerability.

PMID- 30286821
TI  - Timing of Left Ventricular Remodeling in Nonischemic Dilated Cardiomyopathy.
AB  - BACKGROUND: Mineralocorticoid receptor antagonist (MRA) treatment produces
      beneficial left ventricular (LV) remodeling in nonischemic dilated cardiomyopathy
      (NIDCM). This study addressed the timing of maximal beneficial LV remodeling in
      NIDCM when adding MRA. MATERIALS AND METHODS: We studied 12 patients with NIDCM
      on stable beta-blocker and angiotensin-converting enzyme inhibitor/angiotensin
      receptor-blocking therapy who underwent cardiac magnetic resonance imaging before
      and after 6-31 months of continuous MRA therapy. RESULTS: At baseline, the LV
      ejection fraction (LVEF) was 24% (19-27); median [interquartile range]. The LV
      end-systolic volume index (LVESVI) was 63 ml (57-76) and the LV stroke volume
      index (LVSVI) was 19 ml (14-21), all depressed. After adding MRA to the HF
      regimen, the LVEF increased to 47% (42-52), with a decrease in LVESVI to 36 ml
      (33-45) and increase in LVSVI to 36 ml (28-39) (for each, P  < 0 .0001). Using
      generalized least squares analysis, the maximal beneficial remodeling (defined by
      maximal increase in LVEF, the maximal decrease in LVESVI and maximal increase in
      LVSVI) was achieved after approximately 12-16 months of MRA treatment.
      CONCLUSIONS: Adding MRA to a standard medical regimen for NIDCM resulted in
      beneficial LV remodeling. The maximal beneficial remodeling was achieved with 12
      16 months of MRA therapy. These results have implications for the timing of other
      advanced therapies, such as placing internal cardioverter-defibrillators.

PMID- 30286822
TI  - Hematuria and Renal Outcomes in Patients With Diabetic Chronic KidneyDisease.
AB  - BACKGROUND: Hematuria may indicate nondiabetic renal disease in diabetic chronic
      kidney disease (CKD). However, some studies have reported that hematuria is noted
      in diabetic nephropathy and is associated with albuminuria. Hematuria is a risk
      factor for end-stage renal disease in glomerulonephritis, but its prognostic
      value in diabetic CKD is unknown. We investigated the factors associated with
      hematuria and the prognostic value of hematuria in patients with diabetic CKD.
      MATERIAL AND METHODS: We included 1958 patients with type 2 diabetes and CKD
      stages 1-5, and 111 patients underwent renal biopsy. Patients in the biopsied
      cohort were younger and had more severe proteinuria, compared with those in the
      total cohort; hematuria was associated with nondiabetic renal disease. RESULTS:
      In the total cohort, hematuria was observed in 15.0% of the patients and was
      associated with young age, a lower estimated glomerular filtration rate,
      proteinuria, high blood pressure and short diabetes duration. Hematuria was
      significantly associated with an increased risk (hazard ratio 1.39, 95% CI: 1.10
      1.76, P < 0.001) of end-stage renal disease, particularly in patients with CKD
      stages 1-3 or a urine protein-to-creatinine ratio of <1,500mg/g (P for
      interaction < 0.05). The odds ratio of hematuria for rapid renal progression was
      1.81 (95% CI: 1.29-2.53, P < 0.001). CONCLUSIONS: Hematuria is associated with
      nondiabetic renal disease in biopsied patients with diabetic CKD and is
      associated with an increased risk of end-stage renal disease in patients with
      early diabetic CKD.

PMID- 30286823
TI  - Sepsis: An Update on Current Practices in Diagnosis and Management.
AB  - Despite several advancements in care over the last few decades, sepsis continues
      to carry a high morbidity and mortality burden in the United States. With its
      varied presentations, cases of sepsis are likely to be encountered by general
      practitioners in both inpatient and outpatient settings. In the recent years,
      there has been much debate about the appropriate criteria to diagnose patients
      with sepsis with a concurrent change in management guidelines. This article
      reviews definitions, diagnosis and treatment guidelines in current practice in
      the management of patients with sepsis.

PMID- 30286824
TI  - Complications of Cirrhosis in Primary Care: Recognition and Management of Hepatic
      Encephalopathy.
AB  - Approximately 3.7% of patients in primary care settings have chronic liver
      disease, and 18% with chronic liver disease in the specialty care setting have
      cirrhosis. For cirrhotic patients without complications, prognosis is generally
      favorable; increased morbidity and mortality are observed when complications
      (i.e., hepatic encephalopathy [HE]) occur. HE occurs in up to 70% of patients
      with cirrhosis. Neurologic signs in HE span a wide spectrum, from those not
      easily apparent (covert) to more clinically obvious signs (overt). Providers
      should consider overt HE in patients with cirrhosis and signs of impaired
      cognition, confusion, consciousness and/or personality changes, and/or impaired
      memory. Overt HE treatment includes identifying and treating precipitating
      factors and reducing bacterial-derived toxin loads. For acute overt HE, lactulose
      is first-line treatment. To prevent HE recurrence, lactulose plus rifaximin is
      recommended. Patients with cirrhosis and HE often present in primary care;
      recognizing and properly managing HE are important in this setting.

PMID- 30286825
TI  - The Importance of Measuring the Psychological Impact of Psoriasis and How We
      Treat Pediatric Patients With Psoriasis.

PMID- 30286826
TI  - Complement Biomarkers of Hemolytic Uremic Syndrome-If Not One Thing, Maybe
      Another.

PMID- 30286827
TI  - Improving Prognostic Tools for Patients With Myelodysplastic Syndromes.

PMID- 30286828
TI  - Cardiovascular Benefits of Group Sport Interventions: Importance of Improved
      Fitness in Risk Reduction.

PMID- 30286829
TI  - Diagnostic Utility of Complement Serology for Atypical Hemolytic Uremic Syndrome.
AB  - OBJECTIVE: To investigate the clinical utility of a 9-analyte complement serology
      panel (COMS) covering complement function (CH50 and AH50), components (C3, C4),
      factor B (CFB), factor H, and activation markers (C4d, Bb, and soluble membrane
      attack complex) for the diagnosis of atypical hemolytic uremic syndrome (aHUS).
      METHODS: Physician orders for COMS from January 19, 2015, through November 4,
      2016, were reviewed. Demographic characteristics, patient diagnosis, and
      laboratory parameters were recorded. RESULTS: There were 177 COMS orders for 147
      patients. The median patient age was 44.9 years (range, 0.9-88.0 years). Common
      reasons for ordering COMS included monitoring and diagnosis of C3 glomerulopathy
      and renal dysfunction and differentiation of aHUS from other thrombotic
      microangiopathies (TMAs). Forty-four patients had COMS ordered for TMAs: 8 had
      aHUS and all had 1 or more abnormalities within the alternative pathway of
      complement. Although the sensitivity of this finding for the diagnosis of aHUS is
      100%, the specificity is only 28%, with a positive likelihood ratio of 1.39.
      Patients with aHUS had lower CH50, C3, and CFB than did those with secondary non
      aHUS TMA (all P<.01). A combined CFB of 20.9 mg/dL or less and CH50 of 56% or
      less led to sensitivity of 75% with increased specificity of 88.9% and a
      diagnostic odds ratio of 24. CONCLUSION: A COMS abnormality should not be
      interpreted in isolation. In conjunction with clinical presentation, a decrease
      in both CFB and CH50 may be an important clue to support the diagnosis of aHUS.

PMID- 30286830
TI  - Food Allergy: A Comprehensive Population-Based Cohort Study.
AB  - OBJECTIVE: To determine the incidence and temporal trends of food allergies.
      PATIENTS AND METHODS: We performed a historical cohort study to describe the
      epidemiology of food allergies among residents of all ages in Olmsted County,
      Minnesota, during a 10-year period from January 2, 2002, through December 31,
      2011, using the Rochester Epidemiology Project database. Overall incidence and
      trends in biannual incidence rates over time were evaluated. RESULTS: During the
      10-year study period, 578 new cases of food allergies were diagnosed. The average
      annual incidence rate was significantly higher among males compared with females
      (4.1 [95% CI, 3.6-4.5] vs 3.0 [95% CI, 2.7-3.4]; P<.001; per 10,000 person-years;
      3.6 per 10,000 person-years overall). The pediatric incidence rate of food
      allergy increased from 7.0 (95% CI, 6.2-8.9) to 13.3 (95% CI, 10.9-15.7) per
      10,000 person-years between the 2002-2003 and 2006-2007 calendar periods and then
      stabilized at 12.5 and 12.1 per 10,000 person-years in the last 2 calendar
      periods. Milk, peanut, and seafood were the most common allergen in infancy, in
      children between ages 1 and 4 years, and in the adult population, respectively.
      CONCLUSION: This is one of the first population-based studies to examine the
      temporal trends of food allergies. The incidence of food allergies increased
      markedly between 2002 and 2009, with stabilization afterward. Additional
      longitudinal studies are warranted to assess for epidemiological evidence of
      changes in food allergy incidence with changing recommendations for allergenic
      food introduction.

PMID- 30286831
TI  - Outcomes of Percutaneous Coronary Interventions in Patients With Anemia
      Presenting With Acute Coronary Syndrome.
AB  - OBJECTIVE: To study the influence of anemia on long-term outcomes of patients
      with acute coronary syndrome undergoing percutaneous coronary intervention (PCI).
      PATIENTS AND METHODS: The study included 5668 consecutive unique patients with
      acute coronary syndrome who underwent PCI at Mayo Clinic from January 1, 2004,
      through December 31, 2014. The patients were stratified on the basis of the
      presence (hemoglobin [Hgb] level, <13 g/dL in men and <12 g/dL in women) and
      severity (moderate to severe Hgb level, <11 g/dL in men and women) of pre-PCI
      anemia and compared with patients without anemia. The primary outcomes were in
      hospital and long-term all-cause mortality after balancing baseline comorbidities
      using the inverse propensity weighting method. RESULTS: Unadjusted all-cause in
      hospital mortality (4.6% [84 of 1831] vs 2.0% [75 of 3837]) and 5-year follow-up
      mortality (44.4% [509] vs 15.4% [323]) were higher in patients with anemia than
      in those without anemia (P<.001 for both). After applying inverse propensity
      weighting analysis, the all-cause in-hospital mortality (2.0% [37] vs 2.0% [75];
      P=.85) and 5-year mortality (17.8% [203] vs 15.4% [323]; P=.05) were not
      significantly different between patients with and without anemia; however, there
      were higher rates of all-cause 5-year mortality in patients with moderate to
      severe anemia (22.3% [113] vs 15.4% [323]; P<.001) compared with patients without
      anemia. The trend in 5-year mortality was driven by increased noncardiac
      mortality in patients with anemia (10.2% [91] vs 7.1% [148]; P=.04) and moderate
      to severe anemia (10.4% [52] vs 7.1% [148]; P=.006) when compared with nonanemic
      patients. CONCLUSION: After accounting for differences in risk profiles of anemic
      and nonanemic patients, anemia appeared to be an independent risk factor for
      increased long-term all-cause and noncardiac mortality.

PMID- 30286832
TI  - Association of Statin Use With Mortality After Dialysis-Requiring Acute Kidney
      Injury: A Population-Based Cohort Study.
AB  - OBJECTIVE: To investigate the association between statin use and mortality in
      patients with dialysis-requiring acute kidney injury (AKI-D). PATIENTS AND
      METHODS: This nationwide, population-based, retrospective cohort study included
      6091 hospitalized patients with AKI-D (1271 statin users and 4820 statin
      nonusers) retrieved from the National Health Insurance Research Database of
      Taiwan between January 1, 2000, and December 31, 2012. All the patients were
      followed up until December 31, 2013. Primary and secondary outcomes were 1-year
      and in-hospital mortality, respectively. All the primary analyses were performed
      using the intention-to-treat approach. RESULTS: During 1-year follow-up, 492 of
      1271 statin users (38.7%) and 2365 of 4820 statin nonusers (49.1%) died. After
      propensity score matching, statin use was independently associated with lower
      risks of 1-year all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.69-0.9;
      P<.001) and in-hospital all-cause mortality (HR, 0.84; 95% CI, 0.71-0.99; P=.04).
      The survival benefit of statin treatment was dose-dependent and consistent across
      subgroups based on sensitivity analyses. CONCLUSION: Statin use was independently
      associated with reduced risks of 1-year and in-hospital mortality in patients
      with AKI-D. Statin therapy may be beneficial in this patient group. However,
      further clinical trials should be performed to confirm the findings.

PMID- 30286833
TI  - COPD Guidelines: A Review of the 2018 GOLD Report.
AB  - Global Strategy for the Diagnosis, Management, and Prevention of COPD 2018 is a
      consensus report published periodically since 2001 by an international panel of
      health professionals from respiratory medicine, socioeconomics, public health,
      and education comprising the Global Initiative for Chronic Obstructive Lung
      Disease (GOLD). The GOLD documents endeavor to incorporate latest evidence and
      expert consensus and are intended for use as "strategy documents" for
      implementation of effective care for chronic obstructive lung disease (COPD) on a
      global level. The GOLD 2018 report defines COPD as a "common, preventable and
      treatable disease that is characterized by persistent respiratory symptoms and
      airflow limitation that is due to airway and/or alveolar abnormalities, usually
      caused by significant exposure to noxious particles or gases," with the criteria
      of "persistent respiratory symptoms" being a new and controversial inclusion
      since 2017. With the availability of newer pharmacotherapy options, treatment
      recommendations are made on the basis of a review of the latest literature and
      directed by symptom burden and health care utilization. Apart from the change in
      definition, a major shift in the recommendations is the exclusion of severity of
      airflow limitation as one of the major factors in guiding therapy. We review the
      salient features of the GOLD 2018 document and provide commentary on features
      that merit further discussion based on our clinical experience and practice as
      well as literature review current as of February 2018.

PMID- 30286834
TI  - Influence of Renal Function on the Pharmacokinetics, Pharmacodynamics, Efficacy,
      and Safety of Non-Vitamin K Antagonist Oral Anticoagulants.
AB  - With the growing integration of non-vitamin K antagonist oral anticoagulants
      (NOACs) into clinical practice, questions have arisen regarding their use in
      special populations, including groups that may have been underrepresented in
      clinical trials. Patients with renal impairment, particularly in the lower
      echelons of renal function, are one such group. In an effort to elucidate the
      current evidence regarding the use of NOACs in patients with renal impairment, a
      systematic assessment of the literature was performed. The MEDLINE database was
      interrogated for studies and analyses evaluating the influence of renal function
      on the pharmacokinetics, pharmacodynamics, efficacy, and safety of NOACs
      published from January 1, 2000, through August 2, 2017. The 82 relevant
      publications retrieved highlight the diversity in the NOAC class regarding the
      impact of renal function on drug clearance, drug exposures, and clinical trial
      outcomes. In several large clinical trials, subgroup analyses revealed no
      significant differences when patients were stratified by creatinine clearance as
      a measure of renal function. Efficacy findings, in particular, were largely
      aligned with the overall population in the included studies. However, relative
      risks of bleeding were shown to vary, sometimes driven by changes in bleeding
      event rates in the comparator arm (eg, warfarin, enoxaparin). With few
      exceptions, minimal influence of mild renal impairment was observed on the
      relative efficacy and safety of NOACs. Taken together, the evidence suggests that
      the presence of renal impairment merits careful consideration of anticoagulant
      choice but should not deter physicians from appropriate use of NOACs.

PMID- 30286835
TI  - A Relationship Between Proton Pump Inhibitors and Hypomagnesemia?

PMID- 30286836
TI  - In Reply-A Relationship Between Proton Pump Inhibitors and Hypomagnesemia?

PMID- 30286837
TI  - Statin-Associated Achilles Tendon Rupture and Reproducible Bilateral Tendinopathy
      on Repeated Exposure.

PMID- 30286838
TI  - Solitary Lung Nodule.

PMID- 30286839
TI  - Uremic Frost.

PMID- 30286840
TI  - Reflections of Mayo by a Team of Mayo Clinic Artists.
AB  - Recognizing the contribution art has had in the Mayo Clinic environment since the
      original Mayo Clinic Building was finished in 1914, Mayo Clinic Proceedings
      features some of the numerous works of art displayed throughout the buildings and
      grounds on Mayo Clinic campuses as interpreted by the author.

PMID- 30286841
TI  - Voluntary Interruption of Pregnancy in Colombia: Contributions to the Debate from
      Public Mental Health.

PMID- 30286843
TI  - Anxiety and Depression Disorders in Relation to the Quality of Life of Breast
      Cancer Patients with Locally Advanced or Disseminated Stage.
AB  - OBJECTIVE: To evaluate patterns of association between anxiety and depression and
      the different elements of the construct of quality of life, in patients with
      locally advanced breast cancer or disseminated stages METHODS: With a single
      measure over time, HADS and FACIT-B scales were applied in 107 women
      histologically confirmed to have breast cancer, in stages IIB, IIIA, IIIB, IIIC
      and IV. Factor analysis and multidimensional scaling methods were used to analyze
      patterns of association RESULTS: In 84.1% of the patients clinical anxiety was
      found (95%CI, 75.8-90.5%) and clinical depression in 25.2% (95%CI, 17.3-34.6%).
      Factor analysis groups items of the two scales in 4 domains which accounted for
      59% of the total variance, where 2 items (H11 and B8) showed high values of
      uniqueness and low factor loadings. Multidimensional scaling suggests five
      groups, showing proximity between depressive symptoms and physical symptoms, as
      well as between anxious symptoms and related to functionality and social and
      family environment CONCLUSIONS: The HADS in patients with neoplastic disease
      detects a high frequency of depressive and especially anxious symptoms, which
      makes it advisable to reevaluate their psychometric properties in patients with
      cancer. The association between depressive symptoms of HADS and physical symptoms
      of quality of life construct is in favor of the difficulty of diagnosing
      depressive disorder in patients with cancer, so it may be necessary to develop
      instruments that allow locating symptoms or clinical characteristics that
      facilitate this diagnosis.

PMID- 30286842
TI  - Relationship Between Cognitive Function and Clinical Features in Patients With
      Bipolar I Disorder.
AB  - INTRODUCTION: Previous studies suggest that the severity of alterations in
      cognitive functions in people with a diagnosis of bipolar I disorder (BP-I) are
      directly related to the deterioration in overall functioning and life quality.
      Altered cognitive function is associated with a worse prognosis of BP-I, however
      little is known about the relationship between cognitive functions and the
      clinical features of BP-I. OBJECTIVE: To establish possible associations between
      cognitive function and the clinical and socio-demographic characteristics of
      patients with BP-I. METHODS: Cognitive function was evaluated by applying a
      neuropsychological battery to a group of patients with a BP-I diagnosis, who did
      not have affective episodes for at least 6 months, and who were outpatients
      treated at the San Juan de Dios Clinic in Manizales. The statistical analysis
      involved using clustering methocology in order to divide those patients with the
      best and worst cognitive function and it was later correlated with the clinical
      and socio-demographic variables. RESULTS: A statistically significant
      corrrelation was found between the number of years of education and the age the
      disorder started with alterations in the level of cognitive function (P=.002 and
      P=.017 respectively). No significant correlations were found with other
      variables. CONCLUSIONS: An early onset of the pathology and fewer years of
      education seems to be risk factors associated with poorer cognitive function in
      patients with BP-I.

PMID- 30286844
TI  - The Psychopathology of Delusion of Control According to Subjective Experience.
AB  - BACKGROUND: Delusion of control, including thought insertion, occurs in 20% of
      patients with schizophrenia. However little is known of its psychopathology, and
      studies involving patients are scarce. AIMS: To explore the subjective experience
      of patients with delusion of control and to propose a psychopathological
      explanation based on empirical evidence. METHODS: Qualitative exploratory study
      of 7 patients (6 with schizophrenia and 1 with schizophreniform disorder). A
      phenomenologically-oriented semi-structured interview was used. RESULTS: Delusion
      of control is not an isolated and pure symptom; it is always immersed in the
      context of a persecutory delusion and other psychiatric symptoms. The patient
      experiences partial control, i.e. the control is never complete. In all cases, it
      is possible to trace the history of the narrative formation of delusion of
      control from its origins in persecutory delusions and other concomitant symptoms.
      CONCLUSIONS: The delusion of control is a narrative resulting from the joint
      presence of a persecutory delusion and other psychiatric symptoms. For the
      patient, the delusion of control is the narrative of the elaborate expression of
      the meaning of the anomalous experience. Delusion of control is a narrative
      variety of persecutory delusion.

PMID- 30286845
TI  - Anxiety, Self-esteem and Body Image in Girls with Precocious Puberty.
AB  - Currently, the age of onset for pubertal changes is decreasing, especially in
      girls, which may have an impact on psychosocial factors such as anxiety, self
      esteem and body image. The aim of the present study is to compare these variables
      in two groups: a group of 15 girls with precocious puberty and a group of 16
      girls of the same age without precocious puberty. A non-experimental descriptive
      design was used and the State-Trait Anxiety Inventory for Children (STAIC) and
      Self-Description Questionnaire (SDQ) were used to measure variables. Significant
      differences were found in Anxiety and Body Image levels between groups, but there
      were no differences in Self-Esteem levels. In conclusion, the findings show girls
      with early onset pubertal changes present high anxiety levels and negative body
      image compared to girls who start pubertal changes at the normal time.

PMID- 30286846
TI  - Validity and Reliability of the Spanish Version of the Montreal Cognitive
      Assessment (MoCA) for the Detection of Cognitive Impairment in Mexico.
AB  - OBJECTIVE: To establish the validity and reliability of the Montreal Cognitive
      Assessment in Spanish (MoCA-S) to identify mild cognitive impairment (MCI) and
      dementia in the Mexican elderly population. MATERIAL AND METHODS: 168
      participants from a memory clinic in Mexico City were enrolled and divided into 3
      groups: 59 cognitively healthy (CHG), 52 with mild cognitive impairment (MCI)
      (DSM-5 criteria) and 57 with dementia (NINCDS-ADRDA criteria). The MoCA-S and
      Mini-Mental State Evaluation (MMSE) were applied at baseline and during the last
      months to establish intra-observer reliability. ROC curves and a multinomial
      regression model were constructed to evaluate the effect of age and education on
      MoCA-S performance. RESULTS: The mean age of the participants was 76+/-8.1 years
      and the education rate was 10.7+/-5.2. The MoCA-S scores by group were: CHG,
      27.3+/-1.9; MCI, 22.9+/-2.9; and dementia, 13.7+/-4.9 (p<0.001). The reliability
      of the MoCA-S was 0.89 and the intraclass correlation coefficient was 0.955.
      Sensitivity was 80% and specificity was 75%, with a cut-off point of 26 points
      for MCI (area under the curve, 0.886; p<0.001). For the dementia group, the
      sensitivity was 98% and specificity was 93%, with a cut-off point of 24points
      (area under the curve, 0.998; p<0.001). The multinomial regression showed no
      association with education and age for both the MCI and dementia groups.
      CONCLUSIONS: The MoCA-S is a valid and reliable instrument for MCI and dementia
      screening in the Mexican population, even after adjusting for age and education.

PMID- 30286848
TI  - Psycho-Social Evaluation of a Living Kidney Donor.
AB  - The decision to become a living kidney donor is full of conflicts. It is
      generally believed that the candidates are aware of their reasons, that they have
      thought long about it, and have even asked questions about it. Thus it is
      surprising that, in many cases, they are only vaguely aware of their reasons and
      their validity. Sometimes, it is an impulsive decision guided by their emotions
      and entrusted to their luck or faith. Sometimes, they are undecided and put under
      pressure due to various circumstances. The mental health assessment should help
      to clarify their reasons, and to put them into words. It should be a positive
      experience, enriching their decision. It should give the candidate the inner
      feeling of having received help for taking the best decision. The psychosocial
      evaluation should be the first of multiple assessment ratings that the living
      kidney donor must face. A well-taken decision is a requirement to start the
      process properly. The author reviews the conditions in which that interview
      should be developed, the requirements to be met by the decision, and the proper
      techniques to obtain accurate information.

PMID- 30286847
TI  - Psychiatric Disorders Secondary to Neurometabolic Disorders.
AB  - Some diseases secondary to inborn errors of metabolism are associated with
      psychiatric disorders or minor neurological symptoms. The existence of some cases
      with exclusively psychiatric symptoms represents a diagnostic and therapeutic
      challenge. The aim of this article is to describe seven treatable neurometabolic
      disorders that should be taken into account in the psychiatric consultation as
      they manifest with psychiatric symptoms that mask the organic origin of the
      disorder. Homocysteine metabolism and urea cycle disorders, Wilson's disease,
      Niemann-Pick disease Type C, acute porphyria and cerebrotendinous xanthomatosis
      are described. Following an analysis of the literature, a list of psychiatric
      symptoms associated with these disorders are proposed, ranging from insidious
      changes in affective state and thought to atypical symptoms such as visual
      hallucinations, as well as paradoxical effects of antipsychotics or behavioural
      disorders in children and adolescents associated with loss of autonomy. The most
      frequently associated neurological signs, such as alterations in the state of
      consciousness, motor behaviour and balance disorders, catatonia or progressive
      cognitive deficit are also listed. Emphasis is placed on the importance of
      considering resistance to antipsychotic treatment as a warning sign to suspect
      organicity, as well as the significant improvement in psychiatric impairment when
      effective and early treatment is established.

PMID- 30286849
TI  - Factors Associated With Quality of Online Information on Trapeziometacarpal
      Arthritis.
AB  - PURPOSE: People increasingly search the Internet for information about common
      medical problems such as trapeziometacarpal (TMC) joint arthritis. But this
      information can be biased, inaccurate, and misleading. Medical professionals
      should be aware of what patients may be reading about their condition because
      concepts and beliefs can affect symptoms, limitations, and decision making. This
      study sought factors associated with the quality of design and content of health
      information Web sites about TMC arthritis. METHODS: Using 3 search engines we
      entered "thumb arthritis" and measured the quality of design and content of 67
      Web sites using the DISCERN and LIDA tools, dominant tones using the IBM Watson
      Tone Analyzer, and readability, and we recorded Web site characteristics. All but
      1 Web site exceeded the recommended sixth-grade reading level. We created 2
      backward stepwise regression models to identify independent factors associated
      with Web site design and content quality. RESULTS: In multivariable analysis, the
      Web site not having a clear preference for treatment was independently associated
      with greater design and content quality measured by DISCERN. Health On the Net
      (HON) code certification-a code of conduct for medical Web sites-and nonprofit
      Web sites had higher LIDA scores. CONCLUSIONS: Online information on TMC
      arthrosis is difficult to read, often biased in favor of a particular treatment
      and influenced by profit and HONcode. CLINICAL RELEVANCE: Hand surgeons should
      prepare to gently correct misconceptions established or reinforced, in part, by
      material found on the Internet.

PMID- 30286850
TI  - Finger Replantation Optimization Study (FRONT): Update on National Trends.
AB  - PURPOSE: Traumatic digit amputations have an adverse impact on patients' daily
      living. Despite experts advocating for digit replantation, studies have shown a
      continued decrease in rate of replantation. We performed a national-level
      investigation to examine the recent trend of practice for digital replantation.
      METHODS: We used the National Inpatient Sample database under the Healthcare Cost
      and Utilization Project to select adult patients with traumatic digit amputation
      from 2001 to 2014. We calculated the rate of attempted and rate of successful
      digit replantation per year, subcategorizing for digit type (thumb or finger) and
      for hospital type (rural, urban nonteaching, or urban teaching). We also analyzed
      the pattern of distribution of case volume to each hospital type per year. We
      used 2 multivariable logistic regression models to investigate patient
      demographic and hospital characteristics associated with the odds of replantation
      attempt and success. RESULTS: Among the 14,872 adult patients with a single digit
      amputation from 2001 to 2014, only 1,670 (11.2%) underwent replantation. The rate
      of replantation attempt trended down over the years for both thumb and finger
      injuries at all hospital types, despite increasing proportions of cases being
      sent to urban teaching hospitals where they were more than twice as likely to
      undergo replantation. The rate of successful replantation stayed stable for the
      thumb at 82.9% and increased for fingers from 76.1% to 82.4% over the years.
      Patients were more likely to undergo replantation if they had private insurance
      or a higher level of income. Neither hospital case volume nor hospital type was
      predictive of successful replantation. CONCLUSIONS: Although more single-digit
      amputations were treated by urban teaching hospitals with higher likelihood to
      replant, the downward trend in rate of attempt regardless of hospital type
      demonstrates that concentration of case volume is not the solution to reverse the
      declining trend. CLINICAL RELEVANCE: Financial aspects of digit replantation need
      to be considered from both the patients' and the surgeons' perspectives to
      improve delivery of care for digit replantation.

PMID- 30286851
TI  - Pain Management After Carpal Tunnel Release Surgery: A Prospective Randomized
      Double-Blinded Trial Comparing Acetaminophen, Ibuprofen, and Oxycodone.
AB  - PURPOSE: Adequate postoperative pain control in hand surgery is a multifactorial
      issue affecting patient satisfaction, outcomes, and safety. However, prescription
      opioid abuse is becoming an increasingly prevalent problem in the Unites States.
      The purpose of this study was to determine if there was a difference in pain
      levels or pill consumption when using nonopioids, ibuprofen (IBU) and
      acetaminophen (ACE), versus an opioid, oxycodone (OXY), after carpal tunnel
      release (CTR) performed exclusively under local anesthesia without sedation.
      METHODS: Patients scheduled for primary unilateral CTR under local anesthesia
      alone were randomized to receive 10 deidentified opaque capsules of either OXY 5
      mg, IBU 600 mg, or ACE 500 mg after surgery. Both the patient and the surgeon
      were blinded to the distributed medication. Patients reported the worst pain
      experienced daily (0-10 scale), the number of pills consumed daily, and any
      adverse effects from postoperative days 0-5. RESULTS: Analgesic pill-type
      distribution between the 105 patients who completed the study was 37 OXY, 34 IBU,
      and 34 ACE. For the endoscopic CTR group, mean total pills consumed from the day
      of surgery through postoperative day 5 for OXY, IBU, and ACE were 2.9, 4.2, and
      2.7, respectively. The average worst daily pain scores for all days for the OXY,
      IBU, and ACE groups were 2.8, 2.5, and 2.8, respectively. For the open CTR group,
      mean total pills consumed from the day of surgery through postoperative day 5 for
      OXY, IBU, and ACE were 3.7, 5.1, and 4.2, respectively. The average worst daily
      pain scores for all days for the OXY, IBU, and ACE groups were 3.4, 2.5, and 2.3,
      respectively. Four of 5 adverse events were reported by OXY group patients, but
      all were minor with no reoperations or readmissions. CONCLUSIONS: We recommend
      using nonopioids such as ACE and IBU in the postoperative management after CTR
      surgery, and regardless of the medication prescribed, we advise prescribing no
      more than 5-10 pills after surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic
      II.

PMID- 30286852
TI  - Double Motor Nerve Transfer for All Finger Flexion in Cervical Spinal Cord
      Injury: An Anatomical Study and a Clinical Report.
AB  - PURPOSE: To explore the feasibility of restoring all finger flexion after a
      cervical spinal cord injury. METHODS: Double nerve transfer was conducted in 22
      cadaver upper extremities. Donor nerves were the brachialis branch of the
      musculocutaneous nerve and the extensor carpi radialis brevis (ECRB) branches of
      the radial nerve. Recipient nerves were the anterior interosseous nerve (AIN) and
      the flexor digitorum profundus (FDP) branch of ulnar nerve (ulnar-FDP). Nerve
      transfers were evaluated on 3 parameters: surgical feasibility, donor-to
      recipient axon count ratio, and distance from the coaptation site to the muscle
      entry of recipient nerve. A complete C6 spinal cord injury reconstruction was
      accomplished in a patient using a double nerve transfer of ECRB to ulnar-FDP and
      brachialis to AIN. RESULTS: In the cadaver study, nerve transfers from ECRB to
      AIN, brachialis to AIN, and ECRB to ulnar-FDP were all feasible. The transfer
      from the brachialis to ulnar-FDP was not possible. Mean myelinated axon counts of
      AIN, brachialis, ulnar-FDP, and ECRB were 2,903 +/- 1049, 1,497 +/- 606, 753 +/-
      364, and 567 +/- 175, respectively. The donor-to-recipient axon count ratios of
      ECRB to AIN, brachialis to AIN, and ECRB to ulnar-FDP were 0.24 +/- 0.15, 0.55 +/
      0.38, and 0.98 +/- 0.60, respectively. The distance from coaptation of the ECRB
      to the ulnar-FDP muscle entry was shorter than for the other nerve transfers (54
      +/- 14.29 mm). At 18 months, there was restoration of flexion in all fingers and
      functional improvement from double nerve transfer of the brachialis to the AIN
      and the ECRB to the ulnar-FDP. CONCLUSIONS: Restoration of all finger flexion may
      be feasible by the ECRB to ulnar-FDP and brachialis to AIN double nerve transfer.
      CLINICAL RELEVANCE: Double nerve transfer can be used in C6-C7 spinal cord injury
      and patients with lower arm-type brachial plexus injury who have no finger
      flexion but have good brachialis and ECRB.

PMID- 30286854
TI  - Is It Wise to Implant a SAPIEN Transcatheter Heart Valve in a Dysfunctional Right
      Ventricular Outflow Tract?

PMID- 30286853
TI  - 3-Year Outcomes of the Edwards SAPIEN Transcatheter Heart Valve for Conduit
      Failure in the Pulmonary Position From the COMPASSION Multicenter Clinical Trial.
AB  - OBJECTIVES: This study provides the 3-year follow-up results of the COMPASSION
      (Congenital Multicenter Trial of Pulmonic Valve Regurgitation Studying the SAPIEN
      Transcatheter Heart Valve) trial. Patients with moderate to severe pulmonary
      regurgitation and/or right ventricular outflow tract conduit obstruction were
      implanted with the SAPIEN transcatheter heart valve (THV). BACKGROUND: Early
      safety and efficacy of the Edwards SAPIEN THV in the pulmonary position have been
      established through a multicenter clinical trial. METHODS: Eligible patients were
      included if body weight was >35 kg and in situ conduit diameter was >=16 and <=24
      mm. Adverse events were adjudicated by an independent clinical events committee.
      Three-year clinical and echocardiographic outcomes were evaluated in these
      patients. RESULTS: Fifty-seven of the 63 eligible patients were accounted for at
      the 3-year follow-up visit from a total of 69 implantations in 81 enrolled
      patients. THV implantation was indicated for pulmonary stenosis (7.6%),
      regurgitation (12.7%), or both (79.7%). Twenty-two patients (27.8%) underwent
      implantation of 26-mm valves, and 47 patients received 23-mm valves. Functional
      improvement in New York Heart Association functional class was observed in 93.5%
      of patients. Mean peak conduit gradient decreased from 37.5 +/- 25.4 to 17.8 +/-
      12.4 mm Hg (p < 0.001), and mean right ventricular systolic pressure decreased
      from 59.6 +/- 17.7 to 42.9 +/- 13.4 mm Hg (p < 0.001). Pulmonary regurgitation
      was mild or less in 91.1% of patients. Freedom from all-cause mortality at 3
      years was 98.4%. Freedom from reintervention was 93.7% and from endocarditis was
      97.1% at 3 years. There were no observed stent fractures. CONCLUSIONS:
      Transcatheter pulmonary valve replacement using the Edwards SAPIEN THV
      demonstrates excellent valve function and clinical outcomes at 3-year follow-up.

PMID- 30286856
TI  - Have We Found the Right COMBO to Balance Vascular Injury and Healing?

PMID- 30286858
TI  - Performance Goal Criteria for Device Evaluation in Lower Extremity Peripheral
      Vascular Intervention and the Need for Standardized Data Structure: What Is the
      Sound of One Hand Clapping?

PMID- 30286859
TI  - Better Understanding of Tricuspid Regurgitation Induced by Implanted Leads.

PMID- 30286857
TI  - WIRION Embolic Protection System in Lower Extremity Arterial Interventions:
      Results of the Pivotal WISE LE Trial.
AB  - OBJECTIVES: The WISE LE (WIRIONTM EPS in Lower Extremities Arteries) study was
      designed to assess the clinical performance of the WIRION Embolic Protection
      System (EPS) in subjects undergoing lower extremity atherectomy for the treatment
      of peripheral artery disease. BACKGROUND: Embolization is ubiquitous during
      endovascular procedures for lower extremity peripheral artery disease. METHODS:
      The WISE LE was a multicenter study, performed in the United States and Germany.
      The primary endpoint was freedom from major adverse events (MAEs) occurring
      within 30 days post-procedure and was compared with an objective performance goal
      derived from historical atherectomy trials. MAE was defined as a serious adverse
      event that resulted in death, acute myocardial infarction, thrombosis,
      pseudoaneurysm, dissection (grade C or greater), or clinical perforation at the
      filter location, clinically relevant distal embolism, unplanned amputation, or
      clinically driven target vessel revascularization. The study also included a
      histopathological analysis of debris captured by the filter during the
      procedures. RESULTS: The study protocol specified enrollment of 153 patients with
      the primary endpoint successfully met if 18 (12.0%) or fewer MAEs occurred. A pre
      specified interim analysis performed after 103 patients revealed only 2 MAEs, and
      the study was stopped because it had met its pre-determined metric for success.
      Lesion deemed not accessible by the WIRION EPS occurred in 7 patients. Debris of
      <1-mm, 1- to 2-mm, and >2-mm diameter were found in 98%, 22%, and 9% of patients,
      respectively. CONCLUSIONS: The WIRION EPS is safe and noninferior to the pre
      specified performance goal in capturing debris in the vast majority of patients
      and with the use of a broad range of atherectomy systems.

PMID- 30286855
TI  - 1-Year Clinical Outcomes of All-Comer Patients Treated With the Dual-Therapy
      COMBO Stent: Primary Results of the COMBO Collaboration.
AB  - OBJECTIVES: The aim of this study was to evaluate 1-year clinical safety and
      efficacy of the dual-therapy COMBO stent in a large, all-comers patient-level
      pooled cohort. BACKGROUND: The COMBO stent (OrbusNeich Medical, Fort Lauderdale,
      Florida) is a novel stent with abluminal sirolimus elution from a biodegradable
      polymer and a luminal pro-healing anti-CD34+ antibody layer, which attracts
      circulating endothelial progenitor cells. These endothelial progenitor cells can
      quickly mature into normal endothelium, providing rapid endothelialization.
      METHODS: The MASCOT (Multinational Abluminal Sirolimus Coated biO-engineered
      stenT) (N = 2,614, 61 global sites) and REMEDEE (Randomized study to Evaluate the
      safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt
      Post Market Registry) (N = 1,000, 9 European sites) registries are 2 prospective,
      multicenter studies evaluating clinical outcomes after attempted COMBO stent
      placement in all-comer patients undergoing percutaneous coronary intervention. In
      this patient-level pooled analysis we analyzed 1-year target lesion failure
      (TLF), a composite of cardiac death, target vessel myocardial infarction, or
      clinically driven target lesion revascularization. Furthermore, we determined
      predictors of 1-year TLF. RESULTS: A total of 3,614 patients (63.5 +/- 11.2 years
      of age; 23.8% women) were included in this analysis. The prevalence of diabetes
      mellitus was 29.3%, and 54.3% patients presented with acute coronary syndrome.
      The primary endpoint of 1-year TLF occurred in 140 (3.9%) patients, with
      incidence of cardiac death in 1.6%, target vessel myocardial infarction in 1.2%,
      clinically driven target lesion revascularization in 2.2%, and definite stent
      thrombosis in 0.5% patients. Insulin-treated diabetes mellitus, chronic renal
      failure, and American College of Cardiology/American Heart Association lesion
      type B2/C were independent predictors of 1-year TLF. CONCLUSIONS: In this large
      patient-level pooled analysis of patients treated with the dual-therapy COMBO
      stent excellent results at 1-year were observed. (MASCOT - Post Marketing
      Registry [MASCOT]; NCT02183454; Prospective Registry to Assess the Long-term
      Safety and Performance of the COMBO Stent [REMEDEE Reg]; NCT01874002).

PMID- 30286860
TI  - Reply: Better Understanding of Tricuspid Regurgitation Induced by Implanted
      Leads.

PMID- 30286861
TI  - LAMPOON to Facilitate Tendyne Transcatheter Mitral Valve Replacement.

PMID- 30286862
TI  - Quality-of-Life Assessment in the EXCEL Trial.

PMID- 30286863
TI  - Morphological and Biomechanical Consequences of Post-Dilatation Following
      Transcatheter Aortic Valve Replacement: A Pilot Study.

PMID- 30286864
TI  - Histopathologic Insights Into the Honeycomb-Like Structure in the Coronary
      Artery: In Vivo Multimodality Imaging Assessment With Directional Coronary
      Atherectomy.

PMID- 30286865
TI  - Transcatheter Aortic Valve Replacement for Bioprosthetic Aortic Stenosis in
      Pregnancy.

PMID- 30286866
TI  - Retrospective comparison of intracytoplasmic sperm injection outcomes of sperm
      retrieved from a testicular biopsy and freshly ejaculated semen in
      oligozoospermia.
AB  - OBJECTIVE: The aim of this study was to compare fertilisation, pregnancy rates
      and perinatal outcomes in patients undergoing intracytoplasmic sperm injection
      (ICSI) due to oligozoospermia. METHODS: A total of 166 patients with
      oligozoospermia who underwent an ICSI procedure were included in the study. The
      subjects were divided into two groups according to the sperm retrieval technique
      used: group 1, ejaculated semen (n=111); group 2, surgical sperm retrieval
      (n=55). RESULTS: Although the clinical pregnancy rate was lower in group 2, the
      difference was not statistically significant (36.4% vs. 42.3%, p=0.460). The
      difference between fertilisation and take-home baby rates of the groups were not
      significantly different, either (p=0.486, p=0.419, consecutively). CONCLUSION:
      Two different sperm retrieval techniques used for ICSI had no statistically
      significant difference on intracytoplasmic sperm injection outcomes in
      oligozoospermic patients.

PMID- 30286867
TI  - The relationship between inflammation and mean platelet volume in varicocele
      pathophysiology.
AB  - INTRODUCTION: The mean platelet volume (MPV) is an extensively employed
      laboratory indicator related to platelet volume and function in inflammatory
      circumstances. The aim of this study was to assess the relationship between
      inflammation and mean platelet volume in varicocele pathophysiology. METHODS: We
      conducted a recent study, which included 131 varicocele subjects and 82 healthy
      controls. The identification of varicocele was based on the results from both
      physical examination and color Doppler ultrasound. We analyzed some laboratory
      markers including haemogram tests in two groups. RESULTS: There were no
      significant differences in the two groups in terms of baseline characteristics.
      MPV values were statistically higher in the varicocele group (9.73+/-0.86fL) than
      in the control group (9.03+/-0.70fL) (p<0.001). However, no significant
      relationship between MPV and varicocele grade was found. Furthermore, the
      receiver-operating characteristic curve analysis suggested the optimum MPV cut
      off value for patients with varicocele as 9.05, with a sensitivity and
      specificity of 77% and 50%, respectively (p<0.001). CONCLUSION: MPV can offer
      information on varicocele pathophysiology. Increased MPV levels in varicocele
      patients may be associated with inflammation.

PMID- 30286868
TI  - Our urethrocutaneous fistula repair results in adults after hypospadias surgery.
AB  - INTRODUCTION: Our aim was to evaluate and share our urethrocutaneus fistula
      repair results in adult patients who had been operated for hypospadias in their
      childhood. MATERIAL AND METHODS: The data of totally 48 patients who had been
      treated for urethrocutaneous fistula after hypospadias surgery in our department
      from May 2008 to January 2015 analyzed retrospectively. Patients' age at fistula
      repair, age at first hypospadias surgery, fistula size, localization and number,
      distal urethral obstruction status and surgical outcomes of fistula repairs were
      recorded. All patients were controlled three months after the repair for surgical
      outcomes. RESULTS: Fistula repair performed in 45 patients. Mean age was 21.46
      (20-26). Nineteen patients (42.2%) underwent first hypospadias surgery under the
      age of 7 years; 8 patients (17.7%) between 7 and 15 years, 18 patients between 15
      and 20 years. Tubularized incised plate urethroplasty (TIPU) was performed in 40
      patients (88.9%), extragenital tissue was used in 5 patients (11.1%). Twenty two
      patients (48.9%) had 1 or 2 operations, 17 patients (37.8%) had 3-5 operations
      and 6 patients (13.3%) had 6 or more operations. Thirteen (28.9%) coronal, 24
      (53.3%) subcoronal, 6 (13.3%) penile and 2 (4.4%) penoscrotal fistulas were
      observed. While a single fistula was observed in 35 patients, multiple fistulas
      were seen in 10 patients. A fistula diameter les than 5mm was detected in 37
      patients, and larger than 5mm in 8 patients. Fistula recurrence was observed in 3
      patients at follow-up examinations carried out at 3 months postoperatively. The
      number of operations was more than 5, the fistula diameter was larger than 5mm
      and the fistulas were coronal in all three recurrent fistulas. CONCLUSION:
      According to our results fistula size, previous surgery and well-vascularised,
      one or two layer tissue were the important factors in the success of fistula
      repair after hypospadias surgery.

PMID- 30286869
TI  - In silico screening of anthraquinones from Prismatomeris memecyloides as novel
      phosphodiesterase type-5 inhibitors (PDE-5Is).
AB  - OBJECTIVE: Prismatomeris memecyloides Craib (Rubiaceae) is a medicinal plant
      traditionally used by ethnic minorities in Vietnam for the treatment of erectile
      dysfunction (ED). The aim of this study was to investigate the chemical
      compositions and screen in silico its possible inhibitory effect against PDE-5
      which reduced cyclic guanosine-3',5'-monophosphate (cGMP) levels and indirectly
      caused the male ED. METHODS: Separation of natural compounds were carried out on
      chromatographic column with silica gel or reversed phase materials, eluting with
      different solvent gradients. The structures of all isolated compounds were
      elucidated on the basis of spectroscopic data (HR-MS, 1D/2D-NMR). Docking
      simulation study of compound (1-7) was performed by using flexible side chains
      protocol based on Iterated Local Search Global Optimizer Algorithm of
      AutoDock/Vina v.1.1.2. Pharmacokinetic parameters and toxicity prediction were
      also calculated by appropriate softwares. RESULTS: From the methanol extract of
      roots of P. memecyloides collected in Vietnam, seven compounds including four
      anthraquinone/one anthraquinone glycoside namely damnacanthal (1), lucidin-omega
      methyl ether (2), 3-methylalizarin (3), rubiadin-3-methyl ether (4), and 1-O
      methylrubiadin 3-O-primeveroside (5) along with two iridoid glucosides,
      asperulosidic acid (6) and aitchisonide A (7) were isolated. The molecular
      modeling results showed that 5 anthraquinone compounds possess the lowest binding
      energies to PDE-5. The anthraquinone glucoside 1-O-methylrubiadin 3-O
      primeveroside (5) potentially inhibited PDE-5 similarly to commercial PDE-5Is
      sildenafil (SLD) and tadalafil (TLD). Calculated pharmacokinetic results like
      pIC50,pred; miLogP, TPSA, enzyme inhibitory of anthraquinone glucoside (5) were
      similar and even higher to those of the commercial PDE-5 inhibitors. Especially
      the predictive toxicity of 1-O-methylrubiadin 3-O-primeveroside (5) was even
      lower than those of SLD and TLD. CONCLUSION: This is the first study to find a
      scientific-based evidence for the ethnic use of P. memecyloides as medicinal
      plant for the treatment of ED. The result indicates that the anthraquinones
      (damnacanthal (1), lucidin-omega-methyl ether (2), 3-methylalizarin (3) and
      rubiadin-3-methyl ether (4)), especially anthraquinone glycoside (1-O
      methylrubiadin 3-O-primeveroside (5)) are compounds of potential novel drug class
      for the ED treatment.

PMID- 30286870
TI  - [Effects of drug use and anxiety on premature ejaculation in a sample of Spanish
      drug addicts].
AB  - INTRODUCTION: Premature ejaculation may be due to many factors and one of them
      may be drug use. AIMS: The main objective of this study is to show how drug abuse
      affects the ejaculatory response, keeping in mind the different substances
      consumed, the level of anxiety and the period of withdrawal. METHOD: Two samples
      were used, one for men who were addicted to drugs (N=925) and one of non
      consumers (N=82). Both samples were selected from 28 treatment centers. The
      Golombok Rust Inventory of Sexual Satisfaction (GRISS) questionnaire and the
      State Anxiety Trait Questionnaire (STAI) were used. RESULTS: The results show
      that men with a history of consumption obtain higher percentages in premature
      ejaculation compared to non-users (44.3%> 15.9%) and also higher mean scores in
      anxiety (State Anxiety=19.83>11, 89; Trait Anxiety=25.66>12.39). These
      differences were statistically significant (P=.000). The results confirm that the
      withdrawal period does not improve ejaculatory response and having a partner does
      not work as a protective factor in premature ejaculation. CONCLUSIONS: Men with a
      history of drug use are more likely to suffer from premature ejaculation and
      higher levels of anxiety, which does not improve during the period of withdrawal,
      leading to the belief that drug users have personality traits that facilitate
      premature ejaculation and/or that the neurological damages caused by the drugs
      contribute to a decrease in the intravaginal ejaculatory latency, issues that
      should be studied in future investigations.

PMID- 30286871
TI  - The effect of sleeve gastrectomy technique on women's sexual function: A
      prospective study.
AB  - INTRODUCTION: Obesity may lead to a serious deterioration in general quality of
      daily life and sexual functionality. Bariatric surgery is the most effective
      treatment method for obesity and related morbidities so far and it is better than
      some medical treatment modalities. In this study, we aimed to investigate the
      effects of bariatric surgery and especially sleeve gastrectomy, which has been
      currently performed in increasing numbers on female sexual functions and quality
      of life. MATERIALS AND METHODS: A total of 53 patients were included to the
      current study. The participants were selected from eligible individuals who have
      undergone laparoscopic sleeve gastrectomy operation in our center between April
      2014 and March 2015 dates. Age, body weights and body mass indexes (BMIs) of the
      patients were pre-operatively recorded. The patients have completed the Female
      Sexual Function Index (FSFI), Beck Depression Scale and SF-36 (Short form-36)
      forms before and after the surgery. Additionally, post-operative decrease in body
      weights and mean BMI were recorded. RESULTS: Following bariatric surgery, sexual
      functions of the female patients improved and total FSFI scores increased. When
      FSFI scores were analyzed, it was observed that sexual desire, sexual arousal,
      lubrication, orgasm and sexual satisfaction increased, while the pain parameter
      has not changed. CONCLUSION: Recent literature reveals that unfavorable effects
      of increasingly prevalent obesity on sexual functions cannot be denied. We think
      that sleeve gastrectomy can obtain considerable weight loss, improvement in self
      esteem, decrease in anxiety, amelioration in sexual functions and general quality
      of life.

PMID- 30286872
TI  - Retraction notice to "Paraoxonase I polymorphisms and attention/hyperactivity in
      school-age children from Mexico City, Mexico" Environmental Research (2014) 342 
      349.

PMID- 30286873
TI  - Medical Device and Pharmaceutical Industry Employees as Medical Research
      Publication Authors.
AB  - As an editorial policy, medical device and pharmaceutical industry employees are
      generally permitted to publish original scientific research in Arthroscopy
      journal but are not permitted to publish systematic reviews. All authors complete
      the International Committee of Medical Journal Editors Form for Disclosure of
      Potential Conflicts of Interest, which are thoughtfully considered by our
      reviewers and editors and readers. In accord with the American Academy of
      Orthopaedic Surgeons, we believe that "manufacturers of medical devices,
      biologics, drugs, and other items use(d) in the care of the patient...play an
      important role in...the development of new technologies. This collaborative
      effort ensures that patients have the best outcomes through the invention and
      testing of new technology, research, and evaluation of existing technology." Our
      peer-review process mitigates against bias including but not limited to
      commercial bias in the interpretation of scientific research data. In the end,
      our goal is to publish the best science, and as above, industry plays "an
      important role in...(t)his collaborative effort."

PMID- 30286874
TI  - Brian R. Waterman, M.D., Associate Editor.

PMID- 30286875
TI  - Editorial Commentary: Critical Shoulder Angle: Perhaps Not So "Critical" for
      Clinical Outcomes Following Rotator Cuff Repair.
AB  - The critical shoulder angle (CSA) has been associated with the development of
      rotator cuff pathology. More recent studies have also identified a correlation
      between an increased CSA and recurrent tears after arthroscopic rotator cuff
      repair. Although this observation is significant, several studies have failed to
      identify a correlation between CSA and clinical outcomes after rotator cuff
      repair. As a result, the usefulness of this measurement, and the need to address
      it with lateral acromioplasty, remains ill defined. Further research is required
      to demonstrate an association between CSA and clinical outcomes before treatment
      algorithms should be altered.

PMID- 30286876
TI  - Editorial Commentary: SLAP Repair-The Anterosuperior Portal for Anchor Placement
      Is Best.
AB  - The anterosuperior rotator interval portal for SLAP repair anchor placement is
      the perfect balance between obtaining the proper anchor trajectory and respecting
      the rotator cuff integrity.

PMID- 30286877
TI  - Editorial Commentary: Avoid Passive Acceptance of Early Active Range of Motion
      After Arthroscopic Rotator Cuff Repair.
AB  - Following arthroscopic rotator cuff repair there is a balance between allowing
      reliable tendon healing and regaining range of motion. Common rehabilitation
      philosophy requires time for shoulder immobilization combined with passive range
      of motion to avoid shoulder stiffness yet maximize tendon healing.

PMID- 30286878
TI  - Editorial Commentary: Will New Technology Improve Outcomes or Are All-Suture
      Rotator Cuff Surgery Anchors Like a New Set of Golf Clubs? Not a Question for the
      Biomechanics Lab.
AB  - Failure of rotator cuff repairs may be attributed to biological, mechanical, or
      rehabilitative reasons. New all-suture anchors have several theoretical benefits
      that make them potentially attractive for use in rotator cuff repair. As their
      mechanical strength results from the anchor deploying as a button or molly bolt
      against the inner cortical bone, it stands to reason that decortication performed
      for the purposes of improved repair biology may be particularly detrimental to
      the initial time-zero biomechanics of all-suture anchors. It is unclear whether
      the statistically significant all-suture biomechanics seen with and without
      decortication translate clinically.

PMID- 30286879
TI  - Editorial Commentary: Biomechanics of All Suture Anchors: What We Know So Far.
AB  - All suture anchors (ASAs) have proven valuable for soft tissue to bone fixation.
      They have a small footprint and can be inserted in tight spaces where little bone
      is available. Additionally, more ASAs can be inserted in the same amount of bone
      than their larger predecessors, and this may improve the overall biomechanics of
      the repair construct through load sharing at multiple points of fixation. ASAs
      are more dependent on the cortical bone than the cancellous bone where they are
      inserted for fixation. Decortication of this bone should be minimized or avoided,
      and deployed anchors should be seated to the cortical bone as much as possible at
      the time of insertion to avoid later settling with cyclic loading. In anchor
      biomechanical studies, it is important to look at gap formation with cyclic
      loading. This biomechanical property is clinically more significant than
      catastrophic failure because of anchor pullout or suture breakage, which is
      uncommon. Finally, regarding shoulder rotator cuff surgery, biological (healing)
      is our greatest challenge; in general, anchor fixation strength is adequate.

PMID- 30286880
TI  - Editorial Commentary: The Second Side Is as Good as the First After Bilateral
      Rotator Cuff Repair: Preach Patience to the Patients.
AB  - Symptomatic bilateral rotator cuff tears are common. How patients compare and
      rate each shoulder at different time points following staged repair is variable.
      At a minimum of 1-year follow-up after rotator cuff repair, patients should
      expect similar improvement in pain and validated outcome measures for each side.

PMID- 30286881
TI  - Editorial Commentary: The Practical Goal of Arthroscopic Osteosynthesis for the
      Treatment of Unstable Scaphoid Nonunion.
AB  - Arthroscopic reduction with osteosynthesis using bone grafting has become a
      successful alternative to open techniques for the treatment of chronically
      unstable scaphoid nonunions. Several studies have demonstrated that arthroscopic
      techniques are safe and reproducible in addition to causing less soft tissue
      damage and providing promising short- and mid-term results. However, these
      techniques have limitations in restoring normal carpal alignment, especially in
      patients with unstable scaphoid nonunion and carpal collapse deformities,
      although this does not affect the recovery of clinical function. Therefore, the
      practical goal of arthroscopic technique should be kept in mind when treating
      unstable scaphoid nonunions.

PMID- 30286882
TI  - Editorial Commentary: Acetabular Cartilage Repair: A Critically Important
      Frontier in Hip Preservation.
AB  - Articular cartilage damage to the acetabulum is frequently associated with
      femoroacetabular impingement, and there are considerable long-term implications
      for such injury with regard to maintenance of a healthy hip joint and quality of
      life. Developing treatments capable of restoring articular cartilage to
      acetabular cartilage defects is of great importance if hip preservation
      treatments are to be successful. Ideally, such methods should be performed in a
      minimally invasive manner and be capable of restoring durable repair tissue that
      reconstitutes a healthy osteochondral unit and that continues to function
      effectively over the long term.

PMID- 30286883
TI  - Editorial Commentary: Preservation of the Anterior Intermeniscal Ligament Is
      Crucial to Meniscal Function-The Mechanical Role of the Anterior Part of the
      "Meniscal Belt".
AB  - The anterior intermeniscal ligament represents the most anterior part of the
      "meniscal belt" and potentially contributes to shock-absorbing function of the
      menisci and to the transmission of circumferential hoop stresses in the knee.
      Sectioning of the anterior intermeniscal ligament produces mechanical changes
      similar to those observed with meniscal extrusion, with an increase and central
      shift in tibiofemoral contact force.

PMID- 30286884
TI  - Editorial Commentary: Could Time From Injury to Surgery Affect Decision Making
      for Posterior Cruciate Ligament Reconstruction?
AB  - How long should a trial of conservative treatment of posterior cruciate ligament
      injuries continue before surgical intervention? A recent study demonstrates that
      time from injury to surgery could be negatively correlated with graft maturation
      and remnant preservation. Considering the improvements in arthroscopic posterior
      cruciate ligament reconstruction outcomes, early intervention could be considered
      in high functional demand patients with high grades of instability. Yet it
      remains to be seen whether graft maturation and remnant preservation result in
      improved clinical outcomes regardless of the time to surgical intervention.

PMID- 30286885
TI  - Editorial Commentary: Does "No Difference" Really Mean "No Difference"? Not All
      Anterior Cruciate Ligament Transtibial Drilling Techniques Are Created Equal.
AB  - Despite the preponderance of biomechanical data suggesting that independent
      femoral tunnel drilling results in more favorable knee kinematics and superior
      anterior cruciate ligament footprint restoration when compared with transtibial
      tunnel drilling, equivalent clinical outcomes associated with both techniques
      continue to be reported. However, readers could contemplate the meaning of
      "clinical equivalence" and, perhaps, find themselves wanting better ways to
      detect differences between surgical techniques.

PMID- 30286886
TI  - Editorial Commentary: You Have Some (Infrapatellar Branch of the Saphenous)
      Nerve!
AB  - Infrapatellar branches of the saphenous nerve are always present at the
      anteromedial aspect of proximal tibia. Iatrogenic injury to these branches is a
      known consequence of knee surgery, be it an arthroscopic portal, harvesting of a
      hamstring or bone-patellar tendon-bone anterior cruciate ligament graft, or
      opening wedge opening high tibial osteotomy. Their anatomic course can be
      variable. High-resolution ultrasound may provide an improved diagnostic tool for
      better identification.

PMID- 30286887
TI  - Editorial Commentary: Every Cloud Has a Silver Lining...but Silver May Not Be the
      Currency of Choice: The Bioelectric Silver-Zinc Dressing Requires Additional
      Investigation.
AB  - The use of silver in various forms has been advocated for its antibacterial
      properties for centuries, because its toxicity to human cells is considerably
      lower than its toxicity to bacteria. The Greek historian Herodotus recounted how
      the king of Persia, before going to war, among his provisions included boiled
      water stored in flagons of silver, ostensibly to mitigate the risk of foodborne
      infections in his troops. Additionally, recent studies support the use of silver
      to generate an electrical stimulation for promotion of wound healing. These
      concepts have been combined in a proprietary postoperative dressing that is
      promoted to mitigate the risk of postoperative infections.

PMID- 30286888
TI  - Editorial Commentary: Use Remplissage as a "Fill In" for Latarjet in Patients
      With Shoulder Instability and Hill Sachs Lesions.
AB  - Remplissage minimizes recurrence and confers minimal motion loss when applied to
      glenoid defects up to 20% and humeral loss up to 40% in patients with shoulder
      instability. However, variability in the reporting of volume of both glenoid and
      humeral head bone loss deters the formulation of distinct thresholds for
      indications and contraindication for remplissage. However, there appears to be
      little downside in the performance of this "biologic" solution to Hill-Sachs
      lesions.

PMID- 30286889
TI  - Editorial Commentary: Return to Sport After Surgical Treatments of the
      Acromioclavicular Joint Dislocation Seems to Be Almost Perfect in the Literature.
AB  - Systematic reviews identify completed studies that address a research question
      and evaluate the results of these studies to arrive at conclusions about a body
      of research. They should be encouraged because the findings, with power enhanced
      by the larger sample size available from the combined studies, often represent an
      important scientific contribution. The systematic review findings also can be a
      useful background for developing practice guidelines in the future. One of
      limitations of this approach is a risk of publication bias. Studies with negative
      results are more likely to remain unpublished or excluded from the review owing
      to a lack of reporting outcome of the specific interest. Although publication
      bias is difficult to eliminate, it should be addressed by the authors with
      appropriate statistical procedures that may be helpful in detecting its presence.
      Negative results should not be masked by overall good outcomes. This rather long
      caveat relates to a recent review showing that return to sport after surgical
      treatments of acromioclavicular joint dislocation seems to be almost perfect in
      the literature. Perfection is rare, so publication bias could be a limitation of
      the review.

PMID- 30286891
TI  - Free Will.

PMID- 30286890
TI  - Editorial Commentary: Reduce the Failure Risk: A Challenge to Reduce the Risk of
      Using Hybrid Graft in Anterior Cruciate Ligament Reconstruction.
AB  - Hybrid grafting (augmentation of small hamstring autografts with allograft
      tissue) is preferred by many surgeons for anterior cruciate ligament (ACL)
      reconstruction. Although a recent, well-conducted, systematic review reported no
      significant differences in failure risk between hybrid graft and autograft ACL
      reconstruction, a trend toward a greater failure risk using the hybrid graft
      existed in many of the included studies. Three potential causes of hybrid graft
      ACL reconstruction failure that are absent in autograft ACL reconstruction are
      different levels of graft revascularization and ligamentization, differences in
      the tendon-bone healing capacity between the allograft and autograft portions in
      the bone tunnel, and processing of the graft. Research advances in these areas
      will further reduce the failure risk of hybrid graft ACL reconstruction.

PMID- 30286892
TI  - Commercial Aviation Demonstrates that Technology Will Augment and not Replace
      Radiologists.

PMID- 30286893
TI  - Author's Reply.

PMID- 30286894
TI  - Demonstration of Classic Screening Biases, Not Additional Benefit of Annual Over
      Biennial Screening.

PMID- 30286895
TI  - Erratum.

PMID- 30286896
TI  - Adolescents and Perceived Riskiness of Marijuana: Why Care?

PMID- 30286897
TI  - The Importance of Getting the Name Right for Transgender and Other Gender
      Expansive Youth.

PMID- 30286898
TI  - Are the Times A-Changing? Healthcare Coverage and Access for Adolescents and
      Young Adults Since the Affordable Care Act.

PMID- 30286899
TI  - Contemporary Patterns of Marijuana Use and Attitudes Among High School Seniors:
      2010-2016.
AB  - PURPOSE: The goal of this study was to examine changes in contemporary patterns
      of marijuana use and attitudes over time. Given shifts in state-by-state
      marijuana legislation, there is a reason to believe that the patterns of high
      school seniors' marijuana use behavior and attitudes about use have changed from
      2010 to 2016. METHODS: Data are from high school seniors in the 2010-2016 waves
      of Monitoring the Future, a nationally representative, cross-sectional survey in
      the United States. Latent class analysis was used to determine underlying
      patterns of marijuana use and related attitudes. Differences in latent class
      membership were examined across years, and gender and race/ethnicity were also
      examined. RESULTS: Five latent classes were identified: Intolerant Nonusers (49%
      of the sample), Tolerant Nonusers (12%), Disapproving Users (7%), Experimenters
      (6%), and Marijuana Enthusiasts (26%). Class prevalences remained relatively
      stable from 2010 to 2013; beginning in 2014 a significant decrease in prevalence
      was observed for Intolerant Nonusers and significant increases in prevalence were
      observed for Tolerant Nonusers and Marijuana Enthusiasts. Membership in the
      Marijuana Enthusiasts class was consistently more likely for males; Hispanic and
      black adolescents were more likely to be Disapproving Users. CONCLUSIONS:
      Contemporary patterns of marijuana use and attitudes have remained consistent
      over time, however, significant shifts in class prevalence emerged in 2014.
      Findings also suggest that a substantial subgroup of adolescents would benefit
      from prevention and intervention efforts targeting marijuana use and attitudes.

PMID- 30286900
TI  - The Prospective Association Between Electronic Device Use Before Bedtime and
      Academic Attainment in Adolescents.
AB  - PURPOSE: To examine longitudinal associations between five commonly used
      technology devices prior to bedtime and real-life academic outcomes in
      adolescents. METHODS: A total of 853 adolescents were recruited to a three-year
      prospective cohort study, with annual assessments. Academic grades/levels for
      three core subjects (English, Mathematics, and Science) were extracted from
      school records, and standardized (z-scores) were derived at the end of each
      academic year. A validated questionnaire was used to determine the frequency of
      using five types of technology (television viewing, video gaming, mobile
      telephone use, listening to music, and social networking) before bedtime.
      RESULTS: After adjustment, English attainment was the subject most affected by
      prebedtime technology use, where three of five technologies assessed were
      negatively and prospectively associated (social networking [beta = -.07 and p =
      .024], video gaming [beta = -.10 and p = .008], and mobile telephone [beta = -.07
      and p=.017]). Social networking (beta = -.07and p = .042), television viewing
      (beta = -.08 and p = .044), and mobile telephones (beta = -.07 and p = .031) were
      associated with significant impairment in English for girls whereas attainment in
      boys was most impaired by video gaming (beta = -.12 and p = .014). CONCLUSIONS:
      The use of electronic devices by adolescents before bedtime may reduce their
      academic attainment, but apart from video gaming for boys, the negative impact of
      near bedtime technology use on academic performance is small.

PMID- 30286902
TI  - Impact of a Neuroscience-Based Health Education Course on High School Students'
      Health Knowledge, Beliefs, and Behaviors.
AB  - PURPOSE: The purpose of this pilot study was to evaluate the potential of an
      innovative high school neuroscience-based health course for implementation
      feasibility and impact on student outcomes. METHODS: Thirteen teachers from two
      high schools participated in this quasi-experimental pilot study including 395
      students (202 in the intervention classes and 193 in the comparison classes).
      Students completed pre/post online surveys assessing their knowledge, beliefs,
      and behaviors. Our analysis strategy for multi-item measures was to estimate the
      effects of the intervention on latent change scores in structural equation
      models. RESULTS: Students in the neuroscience health classes showed a significant
      increase in neuroscience knowledge as compared to students in the comparison
      group (difference estimate in proportion correct metric, adjusted for covariates
      = .04; 95% confidence interval [.01, .06]). However, none of the other primary
      outcomes showed a significant difference between conditions. Teachers in the
      intervention group were observed implementing the neuroscience and health
      components more often than the self-regulation and growth mindset components.
      Students in the neuroscience group were more likely to mention the importance of
      caring for their brain and its link to health behaviors. CONCLUSIONS: Findings
      demonstrate that information about the link between health behaviors and brain
      functioning can be successfully integrated into a high school health education
      course, although effects on student health beliefs and behaviors were not
      observed. Additional development work should focus on clarifying the theoretical
      mechanisms of change, integrating the neuroscience content with self-regulation
      and growth mindset, and providing additional professional development for
      teachers.

PMID- 30286901
TI  - The Longitudinal Impact of Screen Time on Adolescent Development: Moderation by
      Respiratory Sinus Arrhythmia.
AB  - PURPOSE: To date, little is known about underlying psychophysiological
      contributions to the impact of media content and overall screen time on
      adolescent psychological functioning. In the present study we examine respiratory
      sinus arrhythmia (RSA) as a moderator of the link between specific types of media
      content use, overall media exposure, and the development of internalizing and
      aggressive symptoms in youth. METHODS: A sample of 374 adolescents (mean age =
      15) reported on their media use, internalizing behavior, and aggressive behavior
      at time 1 (2011) and 1-year follow-up (2012). RSA reactivity was gathered during
      a challenging laboratory task. Path analyses were conducted to test the
      hypothesized three-way interaction model between media use, media content, and
      RSA reactivity, separately for internalizing and aggressive problems. RESULTS:
      Significant interactions were found for aggressive, but not prosocial, media
      content. For aggressive content, youth exhibiting RSA withdrawal reported
      significantly greater internalizing and aggressive symptoms when exposed to
      higher amounts of screen time and aggressive content. CONCLUSIONS: These findings
      suggest that profiles of heightened RSA withdrawal may place adolescents at
      greater risk to the negative impact of violent media, whereas prosocial media
      content may not significantly impact youth development of psychopathology.
      Implications for the role of psychophysiology in our understanding of media
      effects are discussed.

PMID- 30286903
TI  - HIV Pre-Exposure Prophylaxis Medication for Adolescents and Young Adults: A
      Position Paper of the Society for Adolescent Health and Medicine.
AB  - Pre-exposure prophylaxis (PrEP) is a biomedical prevention intervention that has
      demonstrated high efficacy in reducing human immunodeficiency virus (HIV)
      transmission. While an increasing number of jurisdictions have endorsed the use
      of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) for PrEP, access to PrEP
      varies widely. Adolescents and young adults (AYAs), especially those at high risk
      of HIV acquisition, such as young gay, bisexual, and other men having sex with
      men (YGBMSM) and individuals living in countries where HIV is endemic, face
      multiple barriers that limit their access to PrEP. This position paper provides
      context and recommendations for the promotion and use of PrEP among AYAs.

PMID- 30286904
TI  - Corrigendum.

PMID- 30286905
TI  - Imaging for Risk Stratification of Sudden Cardiac Death in Patients With
      Arrhythmogenic Cardiomyopathy.

PMID- 30286906
TI  - Improving Risk Stratification by Cardiac Magnetic Resonance Imaging in Heart
      Failure: Is Strain the Missing Link?

PMID- 30286907
TI  - Spotlight on Strain Following Myocardial Infarction.

PMID- 30286908
TI  - Monitoring the Response to Statin Therapy: One Scan at a Time.

PMID- 30286909
TI  - V/Q-SPECT Scintigraphy in Pulmonary Hypertension: Predictor of Mortality Versus
      Trigger for Transplant, A British Versus American Perspective.

PMID- 30286910
TI  - Decision Making With Imaging in Asymptomatic Aortic Regurgitation.
AB  - The authors review the optimal sequence of multimodality imaging studies in
      patients with chronic asymptomatic aortic regurgitation (AR). The initial
      questions in evaluating such patients are: 1) is AR severe; and 2) does it
      significantly impact the left ventricle? Although transthoracic echocardiography
      is usually able to answer these questions, a cardiovascular magnetic resonance
      imaging study might be necessary if the data from echocardiography are
      conflicting or inadequate. If AR is severe and the left ventricle is severely
      dilated, surgery is indicated. If AR is severe but the left ventricle is not
      significantly impacted, echocardiographic exercise testing might unmask symptoms.
      If aortopathy is suspected, cardiovascular magnetic resonance (in younger
      patients) or computed tomography (in older patients) is necessary. In cases where
      AR severity or mechanism are unclear and no additional tests are possible, or if
      there is a potential for aortic valve repair, transesophageal echocardiography is
      appropriate. Finally, it is good practice to define a follow-up plan with the
      patient and referring physician, with an explanation as to what can be expected
      in the future.

PMID- 30286912
TI  - Mismatch Between Diameter Stenosis and Plaque Atheroma Volume: Challenging Glagov
      Phenomenon?

PMID- 30286913
TI  - The Authors Reply.

PMID- 30286911
TI  - Imaging in Heart Transplant Patients.
AB  - Heart transplantation is an accepted treatment for select patients with end-stage
      heart failure. Improvements to immunosuppressive therapies and patient management
      have increased the half-life of heart transplant patients to over 10 years.
      Despite this success, rejection remains the "Achilles heel" of heart
      transplantation. The early detection of acute rejection and cardiac allograft
      vasculopathy are paramount to avoiding graft loss. Unlike in kidney and liver
      transplantation, there are no clinically validated biomarkers for detecting heart
      transplant rejection. Existing methods for monitoring the cardiac allograft are
      invasive. The endomyocardial biopsy is the standard-of-care for monitoring for
      acute rejection but carries risks of complications, and histologic assessment is
      often subjective. Equally, intracoronary angiography remains the standard-of-care
      for detecting cardiac allograft vasculopathy, but it is invasive and less than
      ideally sensitive. Newer echocardiographic techniques, computed tomography,
      magnetic resonance, and positron emission tomography are less invasive than
      conventional biopsy and show promise in excluding rejection thereby potentially
      decreasing the frequency of biopsies in low-risk patients. Intravascular
      ultrasonography and optical coherence tomography, although still invasive,
      improve on the assessment of the coronary tree through increased resolution,
      evaluation of the microvasculature, and visualization of the vessel wall. This
      review outlines the invasive and noninvasive imaging modalities that are employed
      in the routine care of heart transplant patients and examines newer techniques
      that are under evaluation.

PMID- 30286914
TI  - Anti-Inflammatory Therapy and Coronary Artery Calcification Over Time.

PMID- 30286915
TI  - The Authors Reply.

PMID- 30286916
TI  - CMR Global Longitudinal Strain: A Better Tool for Unraveling the Links to Heart
      Failure Mortality.

PMID- 30286917
TI  - Correction.

PMID- 30286918
TI  - Genetic Variants in SGLT1, Glucose Tolerance, and Cardiometabolic Risk.
AB  - BACKGROUND: Loss-of-function mutations in the SGLT1 (sodium/glucose co
      transporter-1) gene result in a rare glucose/galactose malabsorption disorder and
      neonatal death if untreated. In the general population, variants related to
      intestinal glucose absorption remain uncharacterized. OBJECTIVES: The goal of
      this study was to identify functional SGLT1 gene variants and characterize their
      clinical consequences. METHODS: Whole exome sequencing was performed in the ARIC
      (Atherosclerosis Risk in Communities) study participants enrolled from 4 U.S.
      communities. The association of functional, nonsynonymous substitutions in SGLT1
      with 2-h oral glucose tolerance test results was determined. Variants related to
      impaired glucose tolerance were studied, and Mendelian randomization analysis of
      cardiometabolic outcomes was performed. RESULTS: Among 5,687 European-American
      subjects (mean age 54 +/- 6 years; 47% male), those who carried a haplotype of 3
      missense mutations (frequency of 6.7%)-Asn51Ser, Ala411Thr, and His615Gln-had
      lower 2-h glucose and odds of impaired glucose tolerance than noncarriers (beta
      coefficient: -8.0; 95% confidence interval [CI]: -12.7 to -3.3; OR: 0.71; 95% CI:
      0.59 to 0.86, respectively). The association of the haplotype with oral glucose
      tolerance test results was consistent in a replication sample of 2,791 African
      American subjects (beta = -16.3; 95% CI: -36.6 to 4.1; OR: 0.39; 95% CI: 0.17 to
      0.91) and an external European-Finnish population sample of 6,784 subjects (beta
      = -3.2; 95% CI: -6.4 to -0.02; OR: 0.81; 95% CI: 0.68 to 0.98). Using a Mendelian
      randomization approach in the index cohort, the estimated 25-year effect of a
      reduction of 20 mg/dl in 2-h glucose via SGLT1 inhibition would be reduced
      prevalent obesity (OR: 0.43; 95% CI: 0.23 to 0.63), incident diabetes (hazard
      ratio [HR]: 0.58; 95% CI: 0.35 to 0.81), heart failure (HR: 0.53; 95% CI: 0.24 to
      0.83), and death (HR: 0.66; 95% CI: 0.42 to 0.90). CONCLUSIONS: Functionally
      damaging missense variants in SGLT1 protect from diet-induced hyperglycemia in
      multiple populations. Reduced intestinal glucose uptake may protect from long
      term cardiometabolic outcomes, providing support for therapies that target SGLT1
      function to prevent and treat metabolic conditions.

PMID- 30286919
TI  - SGLT1 and Sweet Genetic Insights Into Cardiometabolic Risk.

PMID- 30286920
TI  - Hypoglycemia and Elevated Troponin in Patients With Diabetes and Coronary Artery
      Disease.
AB  - BACKGROUND: Diabetic medications can cause hypoglycemia, which may lead to
      myocardial damage. OBJECTIVES: This study sought to determine whether
      hypoglycemia is associated with higher levels of high-sensitivity cardiac
      troponin T (hsTnT). METHODS: The BARI 2D (Bypass Angioplasty Revascularization
      Investigation 2 Diabetes) trial randomized patients with type 2 diabetes mellitus
      and stable coronary artery disease, and closely followed them for hypoglycemia
      over the first year. Hypoglycemia was classified by maximum severity and
      frequency. hsTnT was measured at baseline and 1 year, and analyzed using
      multivariable regression. RESULTS: Of 1,984 patients, follow-up hypoglycemia was
      absent in 1,026 (52%) patients, mild in 875 (44%), and severe in 83 (4%), and
      occurred less than weekly in 561 (28%) and greater than or equal to weekly in 397
      (20%). hsTnT levels were associated with hypoglycemia: a median of 11.4 ng/l
      (interquartile range [IQR]: 8.1 to 17.3 ng/l) for none, 12.5 ng/l (IQR: 8.3 to
      19.3 ng/l) for mild, and 13.7 ng/l (IQR: 9.9 to 24.9 ng/l) for severe
      hypoglycemia (p = 0.0001); and 12.5 ng/l (IQR: 8.3 to 18.1 ng/l) for less than
      weekly and 13.0 ng/l (IQR: 8.8 to 21.1 ng/l) for greater than or equal to weekly
      hypoglycemia (p = 0.0013). Severe hypoglycemia was associated with 34% higher 1
      year hsTnT levels (p < 0.0001) in unadjusted analysis, 17% higher (p = 0.006)
      after adjustment for baseline factors unrelated to diabetes, and 6% higher (p =
      0.23) after further adjustment for the duration and severity of diabetes.
      Hypoglycemia greater than or equal to weekly was associated with 14% higher hsTnT
      (p = 0.0003) in unadjusted analysis, 12% higher (p = 0.0002) after adjustment for
      baseline factors unrelated to diabetes, and 4% higher (p = 0.16) after adjustment
      for diabetes related factors. CONCLUSIONS: Hypoglycemia was associated with
      elevated hsTnT levels, but this may be due to more severe diabetes in patients
      who developed hypoglycemia, rather than the direct result of hypoglycemia.
      (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI2D];
      NCT00006305).

PMID- 30286921
TI  - Dangers of Hypoglycemia in Cardiac Patients With Diabetes: Time to Switch to
      Safer, Newer Drugs.

PMID- 30286922
TI  - Combining Oral Anticoagulants With Platelet Inhibitors in Patients With Atrial
      Fibrillation and Coronary Disease.
AB  - BACKGROUND: The optimal treatment strategy when combining antiplatelets with oral
      anticoagulants in patients with atrial fibrillation (AF) and myocardial
      infarction (MI) or undergoing percutaneous coronary intervention (PCI) is
      unknown. OBJECTIVES: The authors investigated the risk of bleeding, ischemic
      stroke, MI, and all-cause mortality associated with direct oral anticoagulants
      (DOACs) compared with vitamin K antagonists (VKAs) in combination with aspirin,
      clopidogrel, or both in patients with AF following MI and/or PCI. METHODS: Danish
      nationwide registries were used to identify patients with AF who were admitted
      with a MI and/or underwent PCI, between August 2011 and June 2017, treated with
      OAC in combination with antiplatelet(s). Patients were followed for 12 months or
      until an outcome, study end, or death. Standardized absolute risks were estimated
      on the basis of outcome-specific Cox regression models adjusted for potential
      confounders. Average treatment effects were obtained as standardized absolute
      risk differences (ARD) in risks at 3 and 12 months using the g-formula. RESULTS:
      Overall, 3,222 patients were included in the study population, of which 875 (27%)
      were treated with VKA+single antiplatelet therapy (SAPT), 595 (18%) were treated
      with DOAC+SAPT, 1,074 (33%) were treated with VKA+dual antiplatelet therapy
      (DAPT), and 678 (22%) were treated with DOAC+DAPT. At 3 months, there was a
      significant difference in the absolute risk of MI associated with DOAC+SAPT
      compared with VKA+SAPT (3-month ARD -1.53% (95% confidence interval: -3.08% to 
      0.11%), with no significant differences found regarding bleeding, ischemic
      stroke, and all-cause mortality. Compared with VKA+DAPT, DOAC+DAPT was associated
      with a significantly reduced risk of bleeding (3-month ARD -1.96%, 95% confidence
      interval: -3.46% to -0.88%), with no significant difference in the absolute risk
      of all-cause mortality, stroke, or MI. CONCLUSIONS: In a real-world population of
      AF patients with MI and/or after PCI, the authors found that DOAC in combination
      with DAPT was associated with a significantly decreased risk of bleeding and
      similar thromboembolic protection compared with VKA in combination with DAPT.

PMID- 30286923
TI  - Conundrum of Using Real-World Observational Data to Inform Real-World Conclusions
      About Safety and Efficacy.

PMID- 30286924
TI  - Left Ventricular Diastolic Dysfunction Predicts Mortality in Patients With
      Systemic Sclerosis.
AB  - BACKGROUND: Primary cardiac affection is common and is a major cause of death in
      systemic sclerosis (SSc), but there are knowledge gaps regarding the effect of
      cardiac dysfunction on mortality. OBJECTIVES: The purpose of this study was to
      evaluate diastolic function in a large, unselected SSc cohort and assess the
      effect of diastolic dysfunction (DD) on mortality. METHODS: SSc patients followed
      prospectively at the Oslo University Hospital from 2003 to 2016 with available
      echocardiographies and matched control subjects were included. DD was assessed by
      echocardiography according to the 2016 American Society of
      Echocardiography/European Association of Cardiovascular Imaging guidelines.
      Pulmonary hypertension (PH) was diagnosed by right heart catheterization. Vital
      status was available for all patients. Cox regression analyses with hazards
      ratios (HRs) were conducted. RESULTS: Diastolic function was assessed in 275 SSc
      patients at baseline and in 186 patients at follow-up. At baseline, 46 of the 275
      SSc patients (17%) were diagnosed with DD and 195 (71%) had normal diastolic
      function. After a median follow-up of 3.4 years (interquartile range: 1.6 to 6.2
      years), the proportion of DD increased from 17% to 29%. During follow-up, 57% of
      patients with DD at baseline died, compared with 13% of patients with normal
      diastolic function. At baseline, 86 patients had performed right heart
      catheterization, and 43 were diagnosed with PH; of these 60% deceased. In
      multivariable Cox regression analyses, DD was a stronger predictor of death (HR:
      3.7; 95% CI: 1.69 to 8.14; c-index 0.89) than PH (HR: 2.0; 95% CI: 1.1 to 3.9; c
      index 0.84). CONCLUSIONS: DD is frequent in SSc, and the presence of DD is
      associated with high mortality. DD exceeds PH with respect to predicting
      mortality.

PMID- 30286925
TI  - Diastolic Function in Systemic Sclerosis Patients: A Neglected Issue?

PMID- 30286926
TI  - Emergency Department Visits by Children With Congenital Heart Disease.
AB  - BACKGROUND: Data related to the epidemiology and resource utilization of
      congenital heart disease (CHD)-related emergency department (ED) visits in the
      pediatric population is limited. OBJECTIVES: The purpose of this analysis was to
      describe national estimates of pediatric CHD-related ED visits and evaluate
      medical complexity, admissions, resource utilization, and mortality. METHODS:
      This was an epidemiological analysis of ED visit-level data from the 2006 to 2014
      Nationwide Emergency Department Sample. Patients age <18 years with CHD were
      identified using International Classification of Diseases-9th Revision-Clinical
      Modification codes. We evaluated time trends using weighted regression and tested
      the hypothesis that medical complexity, resource utilization, and mortality are
      higher in CHD patients. RESULTS: A total of 420,452 CHD-related ED visits (95%
      confidence interval [CI]: 416,897 to 422,443 visits) were identified, accounting
      for 0.17% of all pediatric ED visits. Those with CHD were more likely to be <1
      year of age (43% vs. 13%), and to have >=1 complex chronic condition (35% vs.
      2%). CHD-related ED visits had higher rates of inpatient admission (46% vs. 4%;
      adjusted odds ratio: 1.89; 95% CI: 1.85 to 1.93), higher median ED charges
      ($1,266 [interquartile range (IQR): $701 to $2,093] vs. $741 [IQR: $401 to
      $1,332]), and a higher mortality rate (1% vs. 0.04%; adjusted odds ratio: 1.25;
      95% CI: 1.07 to 1.45). Adjusted median charges for CHD-related ED visits
      increased from $1,219 (IQR: $673 to $2,138) to $1,630 (IQR: $901 to $2,799),
      while the mortality rate decreased from 1.13% (95% CI: 0.71% to 1.52%) to 0.75%
      (95% CI: 0.41% to 1.09%) over the 9 years studied. CONCLUSIONS: Children with CHD
      presenting to the ED represent a medically complex population at increased risk
      for morbidity, mortality, and resource utilization compared with those without
      CHD. Over 9 years, charges increased, but the mortality rate improved.

PMID- 30286927
TI  - Big Data for Little Hearts.

PMID- 30286928
TI  - Blood Sugar Regulation for Cardiovascular Health Promotion and Disease
      Prevention: JACC Health Promotion Series.
AB  - The primary objective of this study was to analyze the most up-to-date evidence
      regarding whether and how blood sugar regulation influences cardiovascular health
      promotion and disease prevention by carrying out an umbrella review. Three
      separate, systematic literature searches identified 2,343 papers in total.
      Overall, 44 studies were included for data extraction and analysis. The included
      systematic reviews and meta-analyses published between January 1, 2016, and
      December 31, 2017, were of good to very good quality (median Overview Quality
      Assessment Questionnaire score = 17). Identified evidence suggests that
      cardiovascular disease (CVD) prevention services should consider regulation of
      blood glucose as a key target for intervention. Furthermore, the recommendations
      for effective intervention and service development/training described here for
      prevention of CVD should be adopted into evidence-based practice guidelines.
      Multidisciplinary teams should be formed to deliver multicomponent interventions
      in community-based settings. There may be substantial opportunities for
      integrating CVD and diabetes prevention services.

PMID- 30286930
TI  - The ACC Is Your Advocate.

PMID- 30286931
TI  - Breast Cancer Patients Receiving Anthracycline Chemotherapy and Trastuzumab Have
      Biventricular Dysfunction and Reduced Heart Mass.

PMID- 30286932
TI  - Stable Interatrial Communication Combining Balloon Atrial Septostomy and
      Radiofrequency Catheter Ablation.

PMID- 30286929
TI  - The Changing Landscape of Diabetes Therapy for Cardiovascular Risk Reduction:
      JACC State-of-the-Art Review.
AB  - Type 2 diabetes mellitus (T2D) is a major risk factor for cardiovascular disease
      (CVD), the most common cause of death in T2D. Despite improved risk factor
      control, however, adults with T2D continue to experience substantial excess CVD
      risk. Until recently, however, improved glycemic control has not been associated
      with robust macrovascular benefit. The advent of 2 new classes of
      antihyperglycemic agents, the sodium-glucose cotransporter-2 inhibitors and the
      glucagon-like peptide-1 receptor agonists, and their respective large
      cardiovascular outcome trials, has led to a paradigm shift in how cardiologists
      and heath care practitioners conceptualize T2D treatment. Herein, the authors
      review the recent trial evidence, the potential mechanisms of action of the
      sodium-glucose cotransporter-2 inhibitors and the glucagon-like peptide-1
      receptor agonists, safety concerns, and their use for the primary prevention of
      CVD as well as in diabetic patients with impaired renal function and heart
      failure.

PMID- 30286935
TI  - Low-Thrombogenicity Mechanical Heart Valves: Which Antithrombotic Strategy?

PMID- 30286934
TI  - The Need for Sex-Specific Cutoff Levels for High-Sensitivity Troponins.

PMID- 30286933
TI  - The HEART Score for Suspected Acute Coronary Syndrome in U.S. Emergency
      Departments.

PMID- 30286936
TI  - Reply: The Need for Sex-Specific Cutoff Levels for High-Sensitivity Troponins.

PMID- 30286937
TI  - Reply: Low-Thrombogenicity Mechanical Heart Valves: Which Antithrombotic
      Strategy?

PMID- 30286938
TI  - Amyloidosis in the Era of Mass Spectrometry-Based Proteomics.

PMID- 30286939
TI  - Reply: Amyloidosis in the Era of Mass Spectrometry-Based Proteomics.

PMID- 30286940
TI  - Is quicker better? A NSQIP analysis of anesthesia time and complications
      following tracheostomy placement.
AB  - BACKGROUND: Increased anesthesia time may lead to respiratory complications in
      patients receiving tracheostomy, which contributes to patient morbidity. METHODS:
      The American College of Surgeon's National Surgical Quality Improvement Program
      (ACS-NSQIP) database was queried for cases of planned tracheostomy (CPT 31600)
      from 2005 to 2012. Patients were stratified into quintiles based on anesthesia
      duration. Pearson's chi square, Fischer's exact test, one-way ANOVA, and
      multivariate regression were used to determine the association between patient
      characteristics with pneumonia and ventilator dependence. RESULTS: Out of 752
      patients, 83 patients experienced post-operative pneumonia, and 166 experienced
      ventilator dependence. Following multivariate regression analysis, anesthesia
      quintiles were not significantly associated with pneumonia or ventilator
      dependence. Age (OR 1.03, 95% CI 1.00-1.05, P = .032), dyspnea (OR 2.21, 95% CI
      1.18-4.13; P = .013), pre-operative ventilator dependence (OR 3.08, 95% CI 1.19
      7.98; P = .020), and sepsis (OR 6.68, 95% CI 3.19-14.0; P < .001) remained as
      significant predictors of post-operative ventilator dependence. CONCLUSIONS:
      Faster may not be better-- prolonged anesthesia time does not increase the risk
      of post-operative pneumonia or ventilator dependence in patients receiving a
      planned tracheostomy in the operating room.

PMID- 30286941
TI  - Urgent Evaluation of the Patient With Acute Central Retinal Artery Occlusion.

PMID- 30286942
TI  - Reply.

PMID- 30286943
TI  - Comprehensive Imaging Assessment of Right Ventricular Strain in Acute Pulmonary
      Embolism.

PMID- 30286944
TI  - Stereotactic body radiation therapy (SBRT) for early-stage lung cancer in the
      elderly.
AB  - Early-stage non-small cell lung cancer (NSCLC) is on the rise due to the
      implementation of screening guidelines for patients at risk for developing lung
      cancer. It is anticipated that as the US population continues to age, there will
      be a higher percentage of medically inoperable early-stage lung cancer patients.
      For this reason, noninvasive ablative therapies are necessary. Stereotactic body
      radiation therapy (SBRT) is an effective modality in addressing early-stage
      NSCLC. SBRT consists of high-dose radiation delivered over 3-5 treatments.
      Several randomized trials comparing surgery to SBRT in early-stage operable
      patients have unfortunately closed early due to poor accrual. However, a recent
      pooled analysis from 2 randomized trials (StereoTActic Radiotherapy and
      Radiosurgery Or Surgery for operable Early-stage non-small cell Lung cancer)
      comparing surgery to SBRT did show comparable local control and overall survival
      rates between surgery and SBRT, offering a very effective, noninvasive modality
      for older adult patients with early-stage NSCLC. In this review, we summarize the
      role of SBRT in early-stage NSCLC, in particularly applied to the older adult
      population.

PMID- 30286946
TI  - Self-report of self-disclosure statements for stuttering.
AB  - PURPOSE: To (1) analyze verbatim wording used by adults who stutter (AWS) to self
      disclose stuttering, (2) determine contexts in which AWS may self-disclose, (3)
      examine the use of self-disclosure by AWS about other aspects of their identity,
      and (4) investigate the ways in which speech-language pathologists (SLPs) develop
      self-disclosure statements with AWS. METHOD: Web-based questionnaires were
      administered to AWS (N = 42) and SLPs (N = 33) who work with AWS. The AWS
      questionnaire asked about the verbatim wording of self-disclosure statements used
      by AWS and the contexts in which they utilize them. For SLPs, the questionnaire
      probed how and why they work with AWS to formulate self-disclosure statements.
      Responses were openly coded and then funneled into concepts for analysis.
      RESULTS: The majority of AWS provided verbatim self-disclosure statements which
      were educational in nature. However, when responding to fixed choices and when
      reporting on self-disclosing other aspects of their lives, the majority of
      participants selected a direct statement. The majority of AWS reported that they
      self-disclose when interviewing for a job. SLPs reportedly instruct their clients
      to use educational self-disclosure statements. SLPs also reported that they use
      an individualized approach to brainstorming self-disclosure statements. Finally,
      SLPs reported that they find self-disclosure beneficial because it facilitates
      self-empowerment for AWS. CONCLUSION: AWS may benefit from learning about the
      type of self-disclosure statements and the contexts in which other AWS chose to
      disclose. Additionally, SLPs who work with AWS may benefit from the reported
      procedures for and types of self-disclosure statements formulated by AWS.

PMID- 30286945
TI  - Patterns of FIRST recurrence of stage IIIC1 endometrial cancer with no PARAAORTIC
      nodal assessment.
AB  - OBJECTIVE: To assess the rates and distribution of first recurrence in patients
      with FIGO stage IIIC1 endometrial cancer (EC) who did not undergo paraaortic
      dissection at surgical staging. METHODS: We retrospectively selected all (n =
      207) stage IIIC1 patients treated at a single institution from 5/1993-1/2017.
      Sites of first recurrence were identified, disease-free (DFS) and overall
      survival (OS) calculated, multivariate logistic regression performed to identify
      factors associated with recurrence. RESULTS: Three-year DFS and OS were 66.5% and
      85.7%, respectively. The most common histology was endometroid (64.2%). Three
      year DFS was 81% (SE+/-3.8%) endometrioid vs. 39.5% (SE+/-6.6%) non-endometrioid
      (P < 0.001). Three-year OS was 96.9% (SE+/-1.8%) endometrioid vs. 65.6% (SE+/
      6.7%) non-endometrioid (P < 0.001). Sixty-two (30.1%) patients recurred. Patterns
      of recurrence were: 14 (8.3%) multiple sites, 17 (8.2%) abdominal, 14 (6.8%)
      extra-abdominal, 17 (8.3%) isolated nodal (8 of these (3.9%) paraaortic).
      Patients with isolated tumor cells (ITCs) in lymph nodes only had 12/71 (17%)
      recurrence rate vs. 50/135 (37%) for patients with micro-/macrometastasis. On
      univariate analysis, grade (HR 4.67 95%CI 1.5-14.5, P = 0.008), histology (HR 4.9
      95%CI 2.6-9.3, P < 0.001), myometrial invasion (HR 1.9 95%CI 1.04-3.5, P = 0.04),
      pelvic washing (HR 2.2 95%CI 1.1-4.5, P = 0.03), tumor volume in pelvic LNs (ITC
      vs. micro-/macrometastasis; HR 0.3 95%CI 0.2-0.7, P = 0.003) were associated with
      recurrence. On multivariate analysis, only histology was associated with
      recurrence (HR 7.88 95%CI 3.43-18.13, P < 0.001). CONCLUSIONS: Isolated
      paraaortic recurrence in stage IIIC1 EC is uncommon. Micro-/macrometastasis were
      associated with twice the recurrence rate compared to ITC. These data will help
      clinicians counsel patients with stage IIIC1 EC regarding paraaortic assessment.

PMID- 30286947
TI  - Etomidate as an Induction Agent in Sepsis.
AB  - Sepsis is a life-threatening response to infection often times requiring
      endotracheal intubation in critically ill patients. Etomidate is routinely used
      as an intravenous induction agent to provide sedation and amnesia before placing
      an endotracheal tube. Although etomidate has many favorable qualities, there is a
      major concern regarding the predictable adrenal insufficiency that follows its
      use. Controversy continues to this day as to whether etomidate should be avoided
      in the setting of sepsis or septic shock.

PMID- 30286948
TI  - Systematic Review of Systemic Therapies and Therapeutic Combinations with Local
      Treatments for High-risk Localized Prostate Cancer.
AB  - CONTEXT: Systemic therapies, combined with local treatment for high-risk prostate
      cancer, are recommended by the international guidelines for specific subgroups of
      patients; however, for many of the clinical scenarios, it remains a research
      field. OBJECTIVE: To perform a systematic review, and describe current evidence
      and perspectives about the multimodal treatment of high-risk prostate cancer.
      EVIDENCE ACQUISITION: We performed a systematic review of PubMED, Embase,
      Cochrane Library, European Society of Medical Oncology/American Society of
      Clinical Oncology Annual proceedings, and clinicalTrial.gov between January 2010
      and February 2018 following the Preferred Reporting Items for Systematic Reviews
      and Meta-analysis statement. EVIDENCE SYNTHESIS: Seventy-seven prospective trials
      were identified. According to multiple randomized trials, combining androgen
      deprivation therapy (ADT) with external-beam radiotherapy (EBRT) outperforms EBRT
      alone for both relapse-free and overall survival. Neoadjuvant ADT did not show
      significant improvement compared with prostatectomy alone. The role of adjuvant
      ADT after prostatectomy in patients with high-risk disease is still debated, with
      lack of data from phase 3 trials in pN0 patients. Novel androgen pathway
      inhibitors have been tested only in early-phase trials in addition to primary
      treatment. GETUG 12, RTOG 0521, and nonmetastatic subgroup of the STAMPEDE trial
      showed improved relapse-free survival for docetaxel in patients treated with EBRT
      plus ADT, although mature metastasis-free survival data are still pending. Both
      the SPCG-12 and the VACSP#553 trial showed no improvement in relapse-free
      survival for adjuvant docetaxel after prostatectomy. CONCLUSIONS: In contrast to
      the clearly demonstrated survival benefits of long-term adjuvant ADT when used
      with EBRT, its role after prostatectomy remains unclear especially in pN0
      patients. Adding docetaxel to EBRT-ADT improves relapse-free survival, with
      immature results on overall survival. Novel androgen receptor pathway inhibitors
      are currently being tested in the neoadjuvant and adjuvant setting. PATIENT
      SUMMARY: Treatment of high-risk prostate cancer is based on a multimodality
      approach that includes systemic treatments. The best treatment or therapy
      combination remains to be defined.

PMID- 30286949
TI  - Acceleration of Bone Defect Healing and Regeneration by Low-Intensity Ultrasound
      Radiation Force in a Rat Tibial Model.
AB  - The objective was to evaluate the effect of low-intensity pulsed ultrasound
      (LIPUS)-induced acoustic radiation force on trabecular bone defect repair and
      healing in a rat tibial model. A uniform surgical defect, 3.5 mm in diameter, was
      generated in the proximal bilateral tibial region of rats (N = 20). LIPUS was
      applied to the defects in the left tibia for 20 min every day for 2 wk.
      Contralateral defects in the right tibia served as a control without active LIPUS
      treatment. The micro-computed tomography data revealed that LIPUS-treated tibia
      exhibited higher bone volume/total volume, connectivity density, trabecular
      number, and bone mineral density and significantly lower trabecular separation.
      Histomorphometry analysis indicated a similar trend. Mechanical testing data
      revealed that LIPUS treatment significantly increased bone stiffness relative to
      that of the control group. Short-term (2-wk) LIPUS therapy initiated trabecular
      bone repair and regeneration in large trabecular bone defects, whereas cortical
      bone remained in the initial non-mineralization stage.

PMID- 30286950
TI  - Shear Wave Elastography of Peripheral Muscle Weakness in Patients with Chronic
      Congestive Heart Failure.
AB  - Forty-five study participants (28 chronic heart failure [CHF] patients and 17
      control participants) were prospectively enrolled in this study to investigate
      the clinical potential of ultrasound shear wave elastography (SWE) in identifying
      peripheral muscle weaknesses in chronic heart failure patients. Muscle stiffness
      in the gastrocnemius muscle during extension (stretch) and the lower arm flexor
      muscles during flexion was assessed via shear wave elastography, measuring the
      shear modulus (kPa) for the resting and contractile states in a range of 0-300
      kPa. Resting kPa revealed no significant difference between CHF and CP, but
      exercise kPa for extension and flexion was significantly lower in CHF than CP.
      The area under the receiver operating characteristic curve of the denominator kPa
      Exercise stretch was 0.916, associated with a sensitivity of 89%, a specificity
      of 71% and a corresponding cutoff value of 81.1 kPa. Shear wave elastography is
      thus a reproducible and sensitive ultrasound method for evaluating peripheral
      muscle deficits in patients with CHF.

PMID- 30286951
TI  - Impulsiveness and burn patients.
AB  - OBJECTIVE: Impulsiveness is a tendency to act quickly based on a whim without
      reflection or consideration of consequences. We studied its correlations with
      burn variables and mental disorders among burn patients. METHODS: Consecutive
      acute burn patients (N=107) admitted to the Helsinki Burn Center were assessed
      with the Structured Clinical Interview for DSM-IV mental disorders (SCID) at
      baseline and at 6 months. All patients filled out the 30-item Barratt
      Impulsiveness Scale (BIS-11), the most commonly administered self-report measure
      and a standard point of reference in research on impulsiveness. RESULTS: The mean
      total score of BIS-11 was 64.5 (range 41.0-87.8, SD+/-6.9). There was not a
      significant correlation between impulsiveness and a range of characteristics of
      burn injury (all p-values>0.05). We found a significant correlation between some
      pre-burn mental disorders and impulsiveness, alcohol dependence and attentional
      impulsiveness (OR=1.22, p=0.022), any personality disorder and non-planning
      impulsiveness (OR=1.21, p=0.005), and antisocial personality disorder and motor
      impulsiveness (OR=1.35, p=0.043). Patients with high impulsiveness (total score
      >65) more often than those with low impulsiveness (<=65), had pre-burn mental
      disorders such as major depressive disorder (22.6% vs. 8.6%, p=0.046), alcohol
      dependence (46.9% vs. 25.9%, p=0.023), or other substance dependence (12.2% vs.
      1.7%, p=0.028). CONCLUSION: Impulsiveness had a significant correlation with
      mental disorders but not with burn-related variables. Therefore the role of
      impulsiveness in burn injuries should not be investigated independently without
      first accounting for the role of mental disorders.

PMID- 30286952
TI  - Synthesis, biological evaluation and molecular modeling of a novel series of
      fused 1,2,3-triazoles as potential anti-coronavirus agents.
AB  - Synthesis and biological evaluation of a novel library of fused 1,2,3-triazole
      derivatives are described. The in-house developed multicomponent reaction based
      on commercially available starting materials was applied and broad biological
      screening against various viruses was performed, showing promising antiviral
      properties for compounds 14d, 14n, 14q, 18f and 18i against human coronavirus
      229E. Further in silico studies identified the key molecular interactions between
      those compounds and the 3-chymotrypsin-like protease, which is essential to the
      intracellular replication of the virus, supporting the hypothesis that the
      protease is the target molecule of the potential antiviral derivatives.

PMID- 30286953
TI  - Aspergillus fumigatus phospholipase D may enhance reactive oxygen species
      production by accumulation of histone deacetylase 6.
AB  - Aspergillus fumigatus, an airborne pathogen, causes many diseases, including
      aspergilloma, invasive aspergillosis, and allergic bronchopulmonary
      aspergillosis. Phospholipase D (PLD) is an important virulence factor for A.
      fumigatus infection, but the manner by which PLD contributes to the virulence of
      this pathogen is not clear. Our results show that expression of A. fumigatus PLD
      in human cells was able to increase the production of reactive oxygen species
      (ROS), which play an important role in several signaling pathways as well as in
      lung infection. Meanwhile, A. fumigatus PLD was found to interact with human
      endogenous histone deacetylase 6 (HDAC6), a known regulator of ROS production and
      inflammatory responses; PLD significantly increased the expression level of HDAC6
      protein without altering its mRNA level. These results suggest that A. fumigatus
      PLD may enhance the production of ROS via the accumulation of HDAC6, which may be
      involved in host immunomodulation during A. fumigatus infection.

PMID- 30286954
TI  - The role of UNC5b in ox-LDL inhibiting migration of RAW264.7 macrophages and the
      involvement of CCR7.
AB  - 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.
      The C-C chemokine receptor type 7 (CCR7) is positively correlated with the
      macrophage migration. But the mechanism of CCR7 regulation is not fully
      clearness. In the present study, we demonstrates that expression in UNC5b and
      netrin-1 was enhanced in respond to ox-LDL in Raw264.7 macrophage and associated
      with decreasing cell migration. Interestingly, it was found that ox-LDL
      significantly downregulate CCR7 gene expression. The expression of CCR7 in mRNA
      and protein levels were decreased in ox-LDL treated Raw264.7 macrophage when we
      over expression of UNC5b with pcDNA3.1-UNC5b plasmid. We got the inverse results
      after silence UNC5b gene with siUNC5b. Meanwhile, the data show that in ox-LDL
      inducement, UNC5b down-regulated CCR7, and then inhibited macrophage migration.
      This novel phenomenon is of a crucial highlights to understand deeply the
      pathogenesis of atherosclerosis. The molecular mechanism of CCR7 regulation
      deserves intensive study.

PMID- 30286956
TI  - Serum thyroid hormones levels are significantly decreased in pregnant rats with
      acute pancreatitis.
AB  - Acute pancreatitis in pregnancy (APIP), which was thought to be a rare but severe
      disease, with a high perinatal mortality among maternal-fetuses. Our research
      aimed to study and assess thyroid injury in a rat model of APIP and its possible
      mechanisms. The APIP model was established by retrograde injection with sodium
      taurocholate. Sham-operated (SO) and APIP groups were performed at 3 time-points.
      Histological changes in the maternal thyroid and pancreas were assessed. The
      activities of serum amylase, lipase and levels of FT3, FT4, MDA, TNF-alpha and IL
      1beta were detected in maternal rats, and the expression of MIF, ICAM-1 and CD68
      in the maternal thyroids were determined. In this study, maternal thyroid injury
      as well as pancreas injury occurred in a time-dependent manner. The activities of
      serum amylase, lipase and levels of MDA, TNF-alpha and IL-1beta were markedly
      increased in acute pancreatitis rats, the levels of serum FT3 and FT4 were
      obviously decreased in APIP groups, and the expressions of MIF, ICAM-1 and CD68
      were significantly increased in the thyroid of the APIP group. Ultrastructural
      thyroid injuries were observed in the APIP group. Our research suggests that
      thyroid injury is involved in the rat experimental model of APIP. The degree of
      thyroid dysfunction is associated with APIP, which may affect the prognosis of
      acute pancreatitis.

PMID- 30286955
TI  - Adherens junction-associated pores mediate the intercellular transport of
      endosomes and cytoplasmic proteins.
AB  - Intercellular endosomes (IEs) are endocytosed vesicles shuttled through the
      adherens junctions (AJs) between two neighboring epidermal cells during
      Drosophila dorsal closure. The cell-to-cell transport of IEs requires DE-cadherin
      (DE-cad), microtubules (MTs) and kinesin. However, the mechanisms by which IEs
      can be transported through the AJs are unknown. Here, we demonstrate the presence
      of AJ-associated pores with MTs traversing through the pores. Live imaging allows
      direct visualization of IEs being transported through the AJ-associated pores. By
      using an optogenetic dimerization system, we observe that the dimerized IE
      kinesin complexes move across AJs into the neighboring cell. The AJ-associated
      pores also allow intercellular movement of soluble proteins. Importantly, most
      epidermal cells form dorsoventral-oriented two-cell syncytia. Together, we
      present a model in which an AJ-associated pore mediates the intercellular
      transport of IEs and proteins between two cells in direct contact.

PMID- 30286958
TI  - Common Etiologies of Upper Extremity Spasticity.
AB  - Spasticity is a motor disorder that manifests as a component of the upper motor
      neuron syndrome. It is associated with paralysis and can cause significant
      disability. The most common causes leading to spasticity include stroke,
      traumatic brain injury, multiple sclerosis, spinal cord injury, and cerebral
      palsy. This article discusses the pathophysiology and clinical findings
      associated with each of the most common etiologies of upper extremity spasticity.

PMID- 30286957
TI  - Intrathecal circHIPK3 shRNA alleviates neuropathic pain in diabetic rats.
AB  - Neuropathic pain is one of the most common diabetic complications and
      significantly decrease the quality of life. The aetiology of the painful diabetic
      neuropathic pain is not fully clear. Circular RNAs (circRNAs) have been
      identified as miRNA sponges and involved in various biological processes,
      including pain. CircHIPK3 is a circRNA that have been shown to be an oncogene or
      tumor suppressor to regulate cancer cells growth by sponging multiple miRNAs.
      However, the role of circHIPK3 in diabetic neuropathic pain remains unknown. The
      aim of the present study was to elucidate the possible role of circHIPK3 in the
      control of diabetic neuropathic pain. We found that circHIPK3 are highly abundant
      in serum from diabetes patients who suffered from neuropathic pain and in dorsal
      root ganglion from STZ-induced diabetes rats. Upregulation of circHIPK3 was
      positively associated with grade neuropathic pain in patients with type 2
      diabetes. Silencing circHIPK3 alleviated neuropathic pain in diabetic rats, which
      was involved in neuroinflammation. Further mechanistic investigation demonstrated
      that circHIPK3 interacted with miR-124 and negatively regulated its expression.
      MiR-124 inhibitor can reverse circHIPK3 knockdown-mediated alleviation of
      neuropathic pain and inhibition of neuroinflammation in diabetic rats. We present
      the first evidence that intrathecal circHIPK3 shRNA treatment can be used to
      treat neuropathic pain of diabetic rats.

PMID- 30286959
TI  - Assessment of the Spastic Upper Limb with Computational Motion Analysis.
AB  - This article presents the current status of integrating 3-dimensional motion
      analysis and electromyography to assess upper extremity function clinically. The
      authors used their approach to establish a normative database for 5 Shriners
      Hospital Upper Extremity Evaluation tasks, which provides ranges of motion at the
      point of task achievement. Also, the inter-joint correlations are provided to
      understand the movement coordination required for each task. Distal upper
      extremity motion is strongly related to proximal function, supporting the idea
      that treatment of the proximal upper extremity deficits may be best preceded by
      treatment of the more distal upper extremity segments.

PMID- 30286960
TI  - Nonsurgical Treatment Options for Upper Limb Spasticity.
AB  - There are many nonsurgical treatment options for patients with upper limb
      spasticity. This article presents an algorithmic approach to management,
      encompassing evidence-based rehabilitation therapies, medications, and promising
      new orthotic and robotic innovations.

PMID- 30286961
TI  - Considerations in the Management of Upper Extremity Spasticity.
AB  - Spasticity is a movement disorder characterized by a velocity-dependent increase
      in muscle tone and a hyperexcitable stretch reflex. Common causes of spasticity
      include cerebral palsy, spinal cord injury, and stroke. Surgical treatment plans
      for spasticity must be highly individualized and based on the characteristics of
      patients and the spasticity in order to maximize functional gains. Candidates for
      surgery must be carefully selected. In this article, the authors review the
      pathophysiology of spasticity and discuss general considerations for surgical
      management with an emphasis on patient factors and spasticity characteristics.
      Specific considerations for the common causes of spasticity are presented.

PMID- 30286962
TI  - Surgical Management of Spasticity of the Thumb and Fingers.
AB  - Spasticity of the hand profoundly limits an individual's independent ability to
      accomplish self-care and activities of daily living. Surgical procedures should
      be tailored to patients' needs and functional ability, and even patients with
      severe cognitive injuries and poor upper extremity function may benefit from
      surgery to improve appearance and hygiene. Careful preoperative examination and
      planning are needed, and consideration is given to the potential unintended
      detrimental effect of a surgical procedure on hand function.

PMID- 30286963
TI  - Surgical Management of Spasticity of the Forearm and Wrist.
AB  - Upper extremity spasticity may result from a variety of types of brain injury,
      including cerebral palsy, stroke, or traumatic brain injury. These conditions
      lead to a predictable pattern of forearm and wrist deformities caused by opposing
      spasticity and flaccid paralysis. Upper extremity spasticity affects all ages and
      sociodemographics and is a complex clinical problem with a variety of treatment
      options depending on the patient, the underlying disease process, and
      postoperative expectations. This article discusses the cause, diagnosis,
      operative planning, operative techniques, postoperative outcomes, and
      rehabilitation protocols for the spastic wrist and forearm.

PMID- 30286964
TI  - Surgical Management of Spasticity of the Elbow.
AB  - A spastic limb refers to one with increased tone. This commonly results from an
      upper motor neuron injury, which, in turn, leads to disinhibition of reflex arcs.
      At the level of the elbow, affected individuals typically exhibit a flexion
      posture secondary to spastic contracture of the biceps, brachialis, and
      brachioradialis muscles. Surgical treatment aims to improve access for hygiene,
      function, and cosmetic appearance of the affected limb. The specific surgical
      intervention performed depends on the degree of elbow flexion contracture and
      whether there is an associated joint contracture or soft tissue deficit.

PMID- 30286965
TI  - Surgical Management of Spasticity of the Shoulder.
AB  - Although spastic conditions often involve the shoulder, it is rare for surgical
      intervention to be required. In cases in which chemodenervation and therapy are
      insufficient to optimize the patient's function or minimize their care
      requirements, surgical options, such as tendon and joint releases, can be
      considered. Tendon transfers are rarely indicated. Nerve transfers, particularly
      contralateral C7, may play a larger role in the future as we gain further
      understanding into the risks, indications, and contraindications of this exciting
      technique.

PMID- 30286966
TI  - Management of Joint Contractures in the Spastic Upper Extremity.
AB  - Upper extremity contractures in the spastic patient may result from muscle
      spasticity, secondary muscle contracture, or joint contracture. Knowledge of the
      underlying cause is critical in planning successful treatment. Initial management
      consists of physical therapy and splinting. Botulinum toxin can be helpful, as a
      therapeutic treatment in relieving spasticity and as a diagnostic tool in
      determining the underlying cause of the contracture. Surgical management options
      include release or lengthening of the causative muscle/tendon unit and joint
      capsular release, as required. Postoperative splinting is important to maintain
      the improved range of motion and protect any associated tendon lengthening or
      transfer.

PMID- 30286967
TI  - Technical Pearls of Tendon Transfers for Upper Extremity Spasticity.
AB  - Tendon transfers are an important surgical option when treating patients with
      muscular imbalance due to upper extremity spasticity. A successful surgical
      outcome requires a thorough preoperative clinical evaluation, an understanding of
      tendon transfer biomechanics, appropriate donor and recipient muscle selection,
      technical execution, and postoperative rehabilitation. This article reviews the
      principles, biomechanics, and techniques for commonly performed tendon transfers
      in patients with upper extremity spasticity.

PMID- 30286968
TI  - Selective Neurectomy for the Spastic Upper Extremity.
AB  - Surgery is one element of the rehabilitative care of the spastic upper limb.
      Different surgical techniques have been advocated to address each of the common
      deformities and underlying causes, including muscle spasticity, joint
      contracture, and paralysis. Partial neurectomy of motor nerves has been shown to
      reduce spasticity in the target muscles. It is effective only for the spastic
      component of the deformity, which underscores the importance of a preliminary
      thorough clinical examination. Hyperselective neurectomy, which involves
      performing a partial division of each motor ramus at its entry point into the
      target muscle, results in improved selectivity, reliable partial muscle
      denervation, and durable results.

PMID- 30286969
TI  - Neurosurgical Management of Spastic Conditions of the Upper Extremity.
AB  - Spasticity is a hypertonic segmental reflex pathway caused by a central nervous
      system injury. Spasticity of the upper extremity causes loss of function, joint
      contracture, pain, and poor cosmesis. Treatment aims to reduce or change the
      pathophysiology underlying the hyperactive reflex from dorsal sensory rootlets
      through the intrinsic machinery of the spinal cord to the neuromuscular junction.
      There are many treatments for upper extremity spasticity including oral
      medication, physiotherapy, intrathecal baclofen, and lesional or neuromodulatory
      surgical approaches. Goals of treatment must always be clearly defined, but
      neurosurgical management is most effective when paired with multidisciplinary
      therapies and caregiver participation.

PMID- 30286970
TI  - Management of Spinal Cord Injury-Induced Upper Extremity Spasticity.
AB  - Spasticity affects more than 80% of patients with spinal cord injury. Neural
      mechanisms and musculotendinous alterations lead to typical upper extremity
      features including shoulder adduction/internal rotation, forearm pronation, and
      elbow, wrist, and finger flexion. Long-standing spasticity may lead to soft
      tissue and joint contractures and further impairment of upper extremity function.
      Surgical management involves tendon lengthening, release, and transfer, as well
      as selective neurotomy, in an effort to reduce spastic muscle hypertonicity,
      restore balance, prevent further contracture, and improve posture and function.
      This article summarizes surgical strategies to improve function of the upper
      extremity in patients with tetraplegia.

PMID- 30286971
TI  - Rehabilitation Strategies Following Surgical Treatment of Upper Extremity
      Spasticity.
AB  - Upper motor neuron injuries that occur in cases such as cerebral palsy,
      cerebrovascular accidents, and traumatic brain injury often have resulting upper
      extremity deformity and dysfunction. Multiple surgical options are available to
      improve upper extremity positioning, and, in some cases, motor control.
      Postoperative therapeutic management is imperative to assist the
      patient/caregiver in maximizing potential functional gains. This article provides
      an overview of postoperative guidelines for commonly performed surgeries to
      manage upper extremity dysfunction caused by spasticity and discusses acute
      management as well as therapeutic techniques for functional training and improved
      motor control.

PMID- 30286972
TI  - Outcomes After Surgical Treatment of Spastic Upper Extremity Conditions.
AB  - Surgical interventions for the spastic upper extremity aim to correct the common
      deformities of elbow flexion, forearm pronation, wrist flexion and ulnar
      deviation, and thumb-in-palm deformity. One goal is achieving optimal function
      and improved limb positioning. Aesthetics of the limb have a profound impact on
      self-esteem and satisfaction. Surgical deformity correction has not reliably been
      shown to improve sensory function such as stereognosis. Validated outcome
      measures are used to present outcomes after surgical treatment of the spastic
      upper extremity as it relates to motor function and limb positioning, sensory
      function, and self-esteem.

PMID- 30286974
TI  - Upper Extremity Spasticity.

PMID- 30286973
TI  - The Future of Upper Extremity Spasticity Management.
AB  - Surgical management of upper limb spasticity has traditionally tackled the
      downstream effects at the muscle, tendon, and joint levels. Because this approach
      does not address the underlying pathologic condition within the nerve, surgical
      outcomes have been marked by unsatisfactory relapse over time. Future management
      may focus on reestablishing a normal neuronal impulse pathway to the
      dysfunctional musculotendinous unit. By severing the faulty gamma-neuronal
      circuit at the C7 level, spasticity may be reduced. Transfer of the contralateral
      C7 nerve root to the injured C7 nerve root may open the potential for
      simultaneously restoring extension and improving reach and grasp functions.

PMID- 30286975
TI  - Xylo-oligosaccharides enriched yeast protein feed production from reed sawdust.
AB  - The aim of this study was to convert the cellulose and hemicellulose, in reed
      sawdust from the pulp mills, into yeast protein and xylo-oligosaccharide, then
      functionalize xylo-oligosaccharide as yeast feed. Both synchronous
      saccharification and fermentation and separate hydrolysis and fermentation of
      cellulase and Candida utilis were investigated to produce protein feed. By
      optimizing the fermentation conditions, 6.1 g/L of protein with 76.1% (7.1 g/L)
      xylo-oligosaccharide as the sugar was obtained. The final glucan and xylan
      utilization efficiencies in reed sawdust were 85.45% and 91.03%, respectively.
      Xylo-oligosaccharide enriched yeast protein feed from reed sawdust was thus
      realized by pretreatment, enzymatic hydrolysis and synchronous saccharification
      and fermentation.

PMID- 30286976
TI  - Advantages and disadvantages of the prone position in the surgical treatment of
      supracondylar humerus fractures in children. A literature review.
AB  - INTRODUCTION: Supracondylar humerus fractures are the most common elbow injuries
      in children. The widely adopted approach for Gartland III extension type consists
      of closed reduction and percutaneous pinning; the pin configuration can be
      lateral or crossed in relationship with the habit of the surgeons. Iatrogenic
      injury of the ulnar nerve is the most common risk during the insertion of the
      medial pin. The aim of this study was to analyze advantages and disadvantages of
      percutaneous pinning with the patient in prone position. MATERIALS AND METHODS: A
      literature review of the period 2005-2017 was carried out; four medical search
      engine (Pubmed, Cochrane Library, ISI Web of Science and Scopus) were consulted
      using the review's filter and the key words "Ulnar nerve AND supracondylar
      humerus fractures". The total number of patients were analyzed for: ulnar nerve
      injuries, anesthesiologic management, time of surgery. RESULTS: Twenty-nine
      papers were read, 23 regarding cross pinning in supine position and 6 in prone
      position. On one hand, 1529 children were treated with closed reduction and cross
      pinning in supine position; 69 of these patients (4.5%) suffered from iatrogenic
      ulnar nerve injury. On the other hand, 579 patients underwent the same treatment
      in prone position; no ulnar nerve lesions were reported in this group. Only one
      article compared both groups of children in supine and prone position regarding
      time of anesthesia which is slightly higher in the prone group. There were no
      differences between supine and prone positions regarding x-ray exposition, time
      of surgery, closed reduction manoeuvers, pin positioning, x-ray results, clinical
      and functional results. DISCUSSION AND CONCLUSIONS: The ulnar nerve in children
      is hypermobile in the cubital tunnel and tends to dislocate anteriorly over the
      medial epicondyle, especially when the elbow is in hyperflexion. This may be the
      reason of the increased risk of nerve injury during the insertion of the medial
      pin in supine position and, instead, an advantage of the prone position. The
      insertion of both pins from the lateral side could reduce this complication.
      Larger studies need to be carried out regarding the reported higher duration of
      anesthesia in prone position.

PMID- 30286977
TI  - A case of pembrolizumab-induced autoimmune haemolytic anaemia with polymyalgia
      rheumatica.

PMID- 30286978
TI  - Characterization of Australian Labradoodle dystrophinopathy.
AB  - In humans, dystrophin mutations cause the X-linked recessive disorder known as
      Duchenne muscular dystrophy (DMD). These mutations result in skeletal and cardiac
      muscle damage with mortality increasingly associated with cardiomyopathy. We have
      identified a novel dystrophin mutation in exon 21 in a line of Australian
      Labradoodles; affected dogs develop progressive clinical signs including poor
      weight gain and weight loss, gait abnormalities, exercise intolerance, skeletal
      muscle atrophy, macroglossa, ptyalism, dysphagia, kyphosis, and a plantigrade
      stance. Echocardiographic abnormalities include hyperechoic foci in the left
      ventricular papillary muscles, septal hypokinesis, and decreased left ventricular
      systolic and diastolic volume and internal diameter. Holter recordings found a
      Mobitz type II second-degree atrioventricular (AV) block in one affected dog.
      Analysis of phosphocreatine-to-ATP ratios (PCr/ATP) (obtained via cardiac
      magnetic resonance imaging and spectroscopy evaluation), found no statistically
      significant difference in the mean PCr/ATP between groups. Histopathologic
      skeletal muscle changes included fibrofatty infiltration, myocyte degeneration,
      necrosis, and regeneration, lymphohistiocytic inflammation, and mineralization;
      cardiac changes were limited to a focal area of mineralization adjacent to the
      sinoatrial node in the dog with a second-degree AV block. Due to rapidly
      progressive clinical signs, a severe phenotype, and potential for cardiac
      involvement, Australian Labradoodle dystrophinopathy may be a useful model to
      further study DMD pathogenesis.

PMID- 30286979
TI  - A comparison of lumbar spine and muscle loading between male and female workers
      during box transfers.
AB  - There is a clear relationship between lumbar spine loading and back
      musculoskeletal disorders in manual materials handling. The incidence of back
      disorders is greater in women than men, and for similar work demands females are
      functioning closer to their physiological limit. It is crucial to study loading
      on the spine musculoskeletal system with actual handlers, including females, to
      better understand the risk of back disorders. Extrapolation from biomechanical
      studies conducted on unexperienced subjects (mainly males) might not be
      applicable to actual female workers. For male workers, expertise changes the
      lumbar spine flexion, passive spine resistance, and active/passive muscle forces.
      However, experienced females select similar postures to those of novices when
      spine loading is critical. This study proposes that the techniques adopted by
      male experts, male novices, and females (with considerable experience but not
      categorized as experts) impact their lumbar spine musculoskeletal systems
      differently. Spinal loads, muscle forces, and passive resistance (muscle and
      ligamentous spine) were predicted by a multi-joint EMG-assisted optimization
      musculoskeletal model of the lumbar spine. Expert males flexed their lumbar spine
      less (avg. 21.9 degrees  vs 30.3-31.7 degrees ) and showed decreased passive
      internal moments (muscle avg. 8.9% vs 15.9-16.0%; spine avg. 4.7% vs 7.1-7.8%)
      and increased active internal moments (avg. 72.9% vs 62.0-63.9%), thus producing
      a different impact on their lumbar spine musculoskeletal systems. Experienced
      females sustained the highest relative spine loads (compression avg. 7.3 N/BW vs
      6.2-6.4 N/BW; shear avg. 2.3 N/BW vs 1.7-1.8 N/BW) in addition to passive muscle
      and ligamentous spine resistance similar to novices. Combined with smaller body
      size, less strength, and the sequential lifting technique used by females, this
      could potentially mean greater risk of back injury. Workers should be trained
      early to limit excessive and repetitive stretching of their lumbar spine passive
      tissues.

PMID- 30286980
TI  - Synthesis, characterization and evaluation of reactional parameters on
      substitution degree of N-hexyl-N-methylene phosphonic chitosan.
AB  - N-methylene phosphonic chitosan (NMPC) is treated with hexyl aldehyde to give an
      imine, which is easily converted into N-hexyl-N-methylene phosphonic chitosan
      (HNMPC) under mild conditions. The structure of this new chitosan derivative is
      characterized by FT- IR, 1H, 13C, 31P, 1H13C-HSQC NMR, SEM and XRD. The influence
      of reactional parameters on the substitution degree (DS), evidenced that a mol
      ratio 1.50:1.00 (hexyl aldehyde: free amino groups); a reaction time of 1 h. and
      45  degrees C of temperature afford the best DS. HNMPC molecular weight is
      12,768.62 Da. It shows good emulsifying properties giving o/w emulsions with high
      stability in time. Microscopic observation as well as particle size distribution
      show an unimodal droplet size distribution with low droplet diameters.
      Preliminary tests lead us to believe that this new polymer has good film forming
      properties.

PMID- 30286981
TI  - Integrating 3D-printed PHBV/Calcium sulfate hemihydrate scaffold and chitosan
      hydrogel for enhanced osteogenic property.
AB  - We developed the 3D-printed poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/calcium
      sulfate hemihydrate (PHBV/CaSH) scaffolds by using fused deposition modelling
      (FDM) technique and then coated the scaffolds with chitosan (CS) acetic acid
      solution. After drying and neutralization, CS hydrogel was formed on the surface
      of the scaffolds. The resultant PHBV/CaSH/CS scaffolds could promote the adhesion
      and proliferation of rat bone marrow stromal cells (rBMSCs) and enhance the
      osteogenesis of rBMSCs by up-regulating the expression level of osteogenic genes
      compared to the PHBV and PHBV/CaSH scaffolds. In vivo studies further
      demonstrated the PHBV/CaSH/CS scaffolds could effectively promote new bone
      formation. Therefore, integrating 3D-printed PHBV/CaSH scaffold and CS hrydogel
      represents a novel strategy to promote osteogensis property, showing full
      potential for bone defects repair.

PMID- 30286982
TI  - Synthesis of cyclodextrin polymers containing glutamic acid and their use for the
      synthesis of Ag nanoparticles.
AB  - Crosslinking and functionalizing agents play crucial roles in the
      properties/applications of cyclodextrin polymers. Here we report the synthesis of
      water-insoluble cyclodextrin polymers containing l-glutamic acid. In a first
      route, beta-cyclodextrin was crosslinked with citric acid and subsequently
      functionalized with l-glutamic acid, while a second route involved esterification
      of beta-cyclodextrin with l-glutamic acid, catalyzed by tin octoate. Combined
      evaluation by FTIR, 13C CP/MAS NMR and elemental analysis indicated that the
      sample from the first route had the largest fraction of glutamic acid. Sorption
      tests with methyl orange showed that the cyclodextrin cavities were slightly more
      available in the polymer obtained through the second route. Samples were employed
      as reductant and stabilizer for fast and easy synthesis of silver nanoparticles
      at room temperature. Brief UV irradiation was sufficient for samples produced by
      the first route.

PMID- 30286983
TI  - Comments on "Removal of Cd(??) and phenol using novel cross-linked magnetic
      EDTA/chitosan/TiO2 nanocomposite".

PMID- 30286984
TI  - A mussel-inspired approach towards heparin-immobilized cellulose gel beads for
      selective removal of low density lipoprotein from whole blood.
AB  - In this study, we report a mussel-inspired approach to fabricate heparin
      immobilized cellulose (HeTaCe) gel beads with self-anticoagulative and
      biocompatible properties which can selectively remove low density lipoprotein
      (LDL) from whole blood directly. First, a phase inversion technique was applied
      to prepare cellulose gel beads. Then the as-prepared gel beads were dipped into a
      mixed solution of heparin and tannic acid in phosphate buffered saline (PBS, pH
      8.5) to obtain HeTaCe gel beads. Blood compatibility experiments indicated that
      the HeTaCe gel beads could suppress complement activation as well as contact
      activation and prolong the clotting times to the upper detect limits (activated
      partial thromboplastin time >600 s and thrombin time >180 s) of the automated
      blood coagulation analyzer. An ideal adsorption capacity of LDL in vitro was
      achieved by the HeTaCe gel beads with an amount of 79.1 mg/g. Besides, dynamic
      column adsorption test further demonstrated a selective adsorption of LDL without
      a significant reduction of high density lipoprotein (HDL) in a simulative
      hemoperfusion system. It is believed that the HeTaCe gel beads will be quite
      appealing to future clinical practice aiming at lowering LDL and improving the
      outcomes of patients with high cardiovascular risk.

PMID- 30286985
TI  - Preparation, characterization and in vitro evaluation of melatonin-loaded porous
      starch for enhanced bioavailability.
AB  - The present work aimed to apply porous starch (PS) as carrier to improve the oral
      bioavailability of poorly soluble drug melatonin (MLT). The drug loading and
      encapsulation efficiency of MLT-loaded porous starch (MPS) were optimized. The
      characteristics of MPS were analyzed using scanning electron microscopy, Brunauer
      Emmett-Teller surface area, Fourier-transform infrared spectroscopy, x-ray
      diffraction, differential scanning calorimetry and thermo gravimetric analysis.
      Most MLT transformed into their amorphous form in the PS pores. MPS showed higher
      MLT solubility and cumulative release rate compared with raw MLT in SGF and SIF.
      MPS exhibited a higher inhibition to DCFH-DA-oxidized peroxyl radicals at a lower
      EC50 than that of the raw MLT. Furthermore, the plasma concentrations of MLT and
      MPS reached a Cmax of 134.26 and 291.77 ng/mL at 15 and 20 min, respectively. The
      AUC0-360min of the formulated MPS-treated group was approximately 2.34-fold
      higher than that of raw MLT.

PMID- 30286986
TI  - Structural elucidation and immune-enhancing activity of an arabinogalactan from
      flowers of Carthamus tinctorius L.
AB  - Previous studies showed that polysaccharides from flowers of Carthamus tinctorius
      L. had immunomodulating activities. However, their structures were little known.
      Here, an arabinogalactan, named as HH1-1 with a relative molecular weight of 70.9
      kDa, was isolated from flowers of Carthamus tinctorius L. by hot water
      extraction, followed by purification of a DEAE-Cellulose 32 column and a
      Sephacryl S-200HR column, subsequently. The structure of HH1-1 was evaluated to
      have a backbone of 1,6-linked Galp branched at C-3 by side chain of 1,3-linked
      Galp, with sub-branches attached at its C-3 position. The branches mainly
      contained 1,5-linked, 1,3,5 linked, terminal arabinose and terminal galactose.
      Biological activity assays showed that this polysaccharide had immune-enhancing
      activity by multiple ways, including promoting immune responses by activation of
      NF-kappaB signaling and increasing TNF-alpha, IL-1beta and iNOS expressions in
      lymphocytes and macrophages.

PMID- 30286987
TI  - Protein moiety in oligochitosan modified vector regulates internalization
      mechanism and gene delivery: Polyplex characterization, intracellular trafficking
      and transfection.
AB  - Oligochitosan-modified proteins have gained attention as efficient non-viral
      vectors for gene delivery. However, little information exists if protein moieties
      can serve as an important role for internalization and endosome escape ability of
      the genetic material. To explore this issue, we designed two cationic
      oligochitosan-modified vectors that consist of different proteins, namely a
      hydrophobic plant protein (zein) and a hydrophilic animal protein (ovalbumin
      (OVA)) to deliver pDNA to epithelial cell line CHO-K1 and HEK 293 T. These
      cationic vectors were systematically characterized by molecular weight, infrared
      (IR) structural analysis, transmission electron microscopy (TEM) morphology, and
      surface charge. A remarkable impact of protein moieties was observed on
      physiochemical properties of the developed vectors. Oligochitosan-modified zein
      containing hydrophobic protein exhibited high buffering capacity and excellent
      DNA binding ability compared to the oligochitosan-modified OVA. The data on
      transfection in the presence of endocytic inhibitors indicated that the caveolae
      mediated pathway (CvME) played a key role in the internalization of the zein
      based polyplex. However, the OVA-based polyplex was internalized in CHO-K1 cells
      via CvME and in HEK 293 T cells via the lipid-mediated pathway. Moreover,
      oligochitosan-modified zein exhibited lower cytotoxicity, greater lysosomal
      escape ability, better plasmid stability, and better transfection efficiency than
      the oligochitosan-modified OVA. This study offers a facile procedure for the
      synthesis of cationic vectors and elucidates the relationship that exists between
      protein moieties and transfection activity, thus providing an alternative, non
      viral platform for the gene delivery.

PMID- 30286988
TI  - Sulfated O-polysaccharide with anticancer activity from the marine bacterium
      Poseidonocella sedimentorum KMM 9023T.
AB  - The sulfated polysaccharides are of study interest due to their high structural
      diversity and broad spectrum of biological activity including antitumor
      properties. In this paper, we report on the structural analysis of sulfated O
      specific polysaccharide (OPS) and in vitro anticancer activity of O-deacylated
      lipopolysaccharide (DPS) of the marine-derived bacterium Poseidonocella
      sedimentorum KMM 9023T achieved by a multidisciplinary approach (chemical
      analysis, NMR, MS, and bioassay). The OPS is shown to include two rare
      monosaccharide derivatives: 3-deoxy-9-O-methyl-d-glycero-d-galacto-non-2-ulosonic
      acid (Kdn9Me) and 3-O-acetyl-2-O-sulfate-d-glucuronic acid (D-GlcA2S3Ac). The
      structure of polysaccharide moiety of a previously unknown carbohydrate
      containing biopolymer is established: ->4)-alpha-Kdnp9Me-(2->4)-alpha-d
      GlcpA2S3Ac-(1->. From a biological point of view, we demonstrate that DPS of the
      P. sedimentorum KMM 9023T has no cytotoxicity and inhibits colony formation of
      human HT-29, MCF-7 and SK-MEL-5 cells in a dose-dependent manner. The
      investigated polysaccharide is the second glycan isolated from the bacteria of
      the genus Poseidonocella: previously we studied the OPS of P. pacifica KMM 9010T
      (Kokoulin et al., 2017). Both polysaccharides are sulfated and contain rare
      residues of ulosonic acids. Thus, obtained findings provide a new knowledge about
      kinds and antitumor properties of sulfated polysaccharides and can be a starting
      point for further investigations of mechanisms of anticancer action of
      carbohydrate-containing biopolymers from marine Gram-negative bacteria.

PMID- 30286989
TI  - Bio-inspired consolidants derived from crystalline nanocellulose for decayed
      wood.
AB  - Novel bio-inspired materials derived from crystalline nanocellulose (CNC) have
      been tested as wood consolidants. A suspension of CNC, produced by acid
      hydrolysis of cellulose and used as such or mixed with lignin and/or siloxane
      derivatives (PDMS), was applied on rotted wood samples of Norway spruce. X-Ray
      diffraction analysis on CNC powder showed high crystallinity index. Dynamic light
      scattering (DLS) measurement indicated a nearly uniform particle size
      distribution with an average hydrodynamic diameter for pure CNC smaller than that
      in the mixtures. Raman and FTIR spectroscopies suggested interactions between
      lignin, PDMS and CNC components. The storage modulus of wood samples, measured by
      Dynamic Mechanical Analysis on the same specimen before and after consolidation,
      confirmed the efficiency of pure CNC, which displayed a considerable improvement
      of stiffness. A substantial increase of E' was observed particularly for most
      decayed classes. These results suggest a closer interaction between nanocellulose
      and decayed wood.

PMID- 30286990
TI  - Accurate molar masses of cellulose for the determination of degradation rates in
      complex paper samples.
AB  - Complex cellulosic samples are often difficult to analyse with size-exclusion
      chromatography. The strong molecular associations of hemicelluloses and lignin
      with cellulose produce multimodal molar mass distributions (MMD) that are
      difficult to interpret. More reliable ways of calculating the molar masses of
      cellulose are thus necessary. This is particularly relevant when studying the
      kinetics of paper degradation, as the number average molar mass is the most
      precise indicator. In this study various data handling methods based on the
      deconvolution of bimodal and multimodal MMDs of complex cellulosic samples after
      SEC-MALS-DRI analysis are examined in order to propose more accurate paper
      degradation rates. Two deconvolution methods, which do or do not rely on polymer
      calibration curves were developed and were applied to several kraft and
      groundwood pulp papers unaged and hygrothermally aged. The deconvolution methods
      are discussed and evaluated in light of calculated cellulose activation energies,
      degradation rates and paper usable lifetime predictions.

PMID- 30286991
TI  - Development and characterization of sugar palm nanocrystalline cellulose
      reinforced sugar palm starch bionanocomposites.
AB  - Sugar palm fibre (SPF) was treated with NaClO2, bleached with NaOH and
      subsequently hydrolyzed with acid to obtain sugar palm nanocrystalline cellulose
      (SPNCCs). Bionanocomposites in the form of films were prepared by mixing sugar
      palm starch (SPS) and sorbitol/glycerol with different nanofiller SPNCCs
      compositions (0-1.0 wt%) using solution casting method. The resulting fibres and
      nanocomposites were characterized in terms of morphology (FESEM and TEM),
      footprint, crystallinity (XRD), light transmittance, biodegradability, physical,
      water barrier, thermal (TGA, DSC and DMA) and mechanical properties. The length
      (L), diameter (D) and L/D values of the SPNCCs were 130 +/- 30.23, 8.5 +/- 1.82
      nm, and 15.3, respectively. The SPS/SPNCCs nanocomposite films exhibited higher
      crystallinity, tensile strength, Young's modulus, thermal and water-resistance
      compared to the neat SPS film. The results showed that the tensile strength and
      moduli of the bionanocomposites increased after being reinforced with SPNCCs and
      the optimum nanofiller content was 0.5%.

PMID- 30286992
TI  - Preparation of nano-hydroxyapatite/chitosan aqueous dispersions: From lab scale
      to continuous production using an innovative static mixer.
AB  - Chitosan is widely used in the preparation of organic-inorganic composite
      materials, such as n-HAp/CS composites, which find application for bone
      regeneration. The methods for their preparation are various, and usually based on
      the preparation of intermediate n-HAp/CS dispersions, which can greatly influence
      the final properties of the resulting composites since it is expected that
      homogenous and stable dispersions lead to composite materials with improved final
      properties. This work hypothesizes that, additionally to process parameters such
      as pH, n-HAp/CS weight ratio, mixing conditions and the presence of salts,
      chitosan itself has a high impact on dispersions stability. Thus, the importance
      of properly control the preparation of the n-HAp/CS intermediate dispersions is
      highlighted by doing a systematic study where relevant processing parameters were
      studied at lab scale using ultrasonication, alone or in the presence of chitosan,
      namely on particle size and zeta potential. Furthermore, and based on the best
      laboratorial conditions, the production of n-HAp/CS nanocomposite dispersions in
      continuous mode was attempted through NETmix(r) technology, an innovative static
      mixer and reactor developed at the Associate Laboratory LSRE-LCM of the Faculty
      of Engineering of the University of Porto (FEUP).

PMID- 30286993
TI  - Polymeric blends of hydrocolloid from chia seeds/apple pectin with potential
      antioxidant for food packaging applications.
AB  - The aim of this study was to investigate the antioxidant, mechanical and physical
      properties of a new film-based polymeric blend of hydrocolloids obtained from the
      aqueous extraction of chia seeds (source antioxidants) and apple pectin. The
      individual matrices films were brittle and rigid with poor mechanical properties.
      The blends formulations contributed to improved mechanical properties regarding
      workability and resistance. The antioxidant results showed the potential
      hydrocolloid from chia seeds as natural source of antioxidant in these polymeric
      films. The formulation 3
      (14(hydrocolloid):41(pectin):25(glycerol):20(glutaraldehyde) displayed well
      thermal, mechanical, morphological and antioxidant properties, suggesting their
      great potential for food packaging.

PMID- 30286994
TI  - A holistic approach to unravelling chondroitin sulfation: Correlations between
      surface charge, structure and binding to growth factors.
AB  - Chondroitin sulfate (CS) is a relevant family of polysaccharides that
      participates in a large variety of biological events that are related to neural
      processes by regulating various growth factors through the pattern and degree of
      sulfation of the polysaccharide. However, their own complexity makes their
      optimization for biomedical applications a difficult undertaking. Thus, a
      different perspective has to be taken. Herein, we show that the particular
      sulfate distribution within the disaccharide repeating-unit plays a key role in
      the binding of growth factors (GFs). In particular, this disposition modulates
      the surface charge of the helical structure that, interestingly, has a
      significant influence on the binding capacity of CSs with several GFs. This fact
      should be carefully considered in the design of new ligands with improved
      activity as GFs ligands.

PMID- 30286995
TI  - Enhanced antibacterial profile of nanoparticle impregnated cellulose foam filter
      paper for drinking water filtration.
AB  - Filtration is a promising water treatment method to purify drinking water. To
      develop highly efficient drinking water filter paper, water-resistant cellulose
      foam paper with a high wet strength property was fabricated using diverse metal
      oxide (e.g., copper oxide (CuO), zinc oxide (ZnO), and silver oxide (Ag2O))
      nanoparticles. These nanoparticles were synthesized using the hydrothermal
      reaction method. Their morphological structures were studied using a field
      emission scanning electron microscope (FESEM). The presence of coated
      nanoparticles on the cellulose foam filter was verified by energy dispersive X
      ray spectroscopy (EDX) methods. The antibacterial performance of different types
      of modified cellulose foam filters was studied against E. coli, P. aeruginosa, B.
      subtilis, and B. cereus strains using the zone of inhibition test. The
      antibacterial profile of the cellulose foam filter impregnated with Ag2O
      nanoparticles, when tested against different types of bacteria, exhibited higher
      antibacterial activity than the cellulose foam filter impregnated with ZnO and
      CuO nanoparticles.

PMID- 30286996
TI  - Synthesis of a new superabsorbent copolymer based on acrylic acid grafted onto
      carboxymethyl tragacanth.
AB  - In this research, a new superabsorbent copolymer was synthesized based on the
      tragacanth gum (TG) via graft polymerization of the acrylic acid onto the
      carboxymethyl tragacanth (CMT) in the aqueous solution. For this purpose firstly,
      the carboxymethyl tragacanth was synthesized by reaction of the tragacanth gum
      and the monochlroroacetic acid in basic conditions. Then the acrylic acid was
      grafted on the carboxymethyl tragacanth via free radical polymerization. The
      characterization of the products was carried out by FT-IR, TGA, and SEM analyses.
      The effects of reaction conditions such as different values of the initiator,
      monomer and crosslinking agent on water absorbency were investigated.
      Furthermore, the swelling behavior of the synthesized polymer was evaluated in
      normal saline, tap water, distilled water, at different pHs and in various
      degrees of neutralization of the acrylic acid. Finally, by studying the obtained
      results, optimum conditions for the copolymer with the highest swelling ratio
      were obtained.

PMID- 30286997
TI  - Structural characterization of the surface-associated heteropolysaccharide of
      Lactobacillus plantarum TMW 1.1478 and genetic analysis of its putative
      biosynthesis cluster.
AB  - Microbial exopolysaccharides (EPS) like xanthan are widely exploited as natural
      biopolymers in diverse industrial sectors. In foods, in-situ EPS formation by
      starter cultures allows the manufacturing of "clean labeled" products with
      improved textural and nutritional properties. We performed structural analyses of
      the cell surface-associated EPS produced by Lactobacillus plantarum TMW 1.1478,
      which is a promising starter culture for fermented foods. Chromatographic
      analyses and NMR experiments suggested an acetylated heptameric repeating unit
      comprised of glucose, rhamnose and galactose as major components, whereas
      analysis of the macromolecular HePS structure suggested an apparent molecular
      mass of Mr ~2 * 106 and a root mean square (RMS) radius of ca. 60 nm. Genetic
      analyses enabled the identification of the respective EPS biosynthesis cluster,
      and its modular organization supports the chemically identified, novel EPS
      structure. The obtained results broaden the understanding of complex EPS
      formation from activated sugar nucleotides by Lactobacillus plantarum.

PMID- 30286998
TI  - Cytocompatible chitosan based multi-network hydrogels with antimicrobial, cell
      anti-adhesive and mechanical properties.
AB  - Hydrogel with good mechanical and biological properties has great potential and
      promise for biomedical applications. Here we fabricated a series of novel
      cytocompatible chitosan (CS) based double-network (DN) and triple-network (TN)
      hydrogels by physically-chemically crosslinking methods. Natural polysaccharide
      CS with abundant resources was chosen as the first network due to its good
      antimicrobial activity, biocompatibility and easy cross-linking reaction.
      Zwitterionic sulfopropylbetaine (PDMAPS) was chosen as the second network due its
      good biocompatibility, antimicrobial and antifouling properties. And nonionic
      poly(2-hydroxyethyl acrylate) (PHEA) was chosen as the final network due to its
      good biocompatibility, excellent nonfouling and mechanical properties. Cross
      section SEM images showed that both CS/PHEA (DN1, the molar ratio of
      glutaraldehyde to structural unit of CS is 0.2/3.0) and CS/PDMAPS/PHEA (TN1, the
      molar ratio of glutaraldehyde to structural unit of CS is 0.2/3.0) hydrogels
      exhibited a smooth and uniformly dispersed porous microstructures with pore size
      distribution in the range of 20~100 MUm. The largest compressive stress and
      tensile stress of DN1 hydrogels reached 84.7 MPa and 292 kPa, respectively, and
      largest compressive stress and tensile stress of TN1 hydrogels could reach 81.9
      MPa and 384 kPa, respectively. Moreover, the value of failure strain for TN1 gels
      reached 1020%. Besides excellent mechanical properties, DN1 and TN1 gels
      exhibited good antimicrobial, cytocompatible and antifouling properties due to
      introduction of antimicrobial chitosan, cell anti-adhesive PDMAPS and PHEA. The
      combination of the excellent mechanical and biological properties of multiple
      network hydrogels can provide a potential pathway to develop biomedical hydrogels
      as promising bioapplications in wound dressing and other biomedical applications.

PMID- 30286999
TI  - 6-Maleimidohexanoic acid-grafted chitosan: A new generation mucoadhesive polymer.
AB  - This study aims to synthesize and evaluate a new generation mucoadhesive polymer,
      6-maleimidohexanoic acid-grafted chitosan; MHA-CS, for transmucosal drug delivery
      compared with a well-known mucoadhesive polymer, Cys-CS. The successful synthesis
      was confirmed by nuclear magnetic resonance (NMR) spectroscopy and Fourier
      transform infrared (FT-IR) spectroscopy. Gel permeation chromatography (GPC) was
      used to determine the molecular weight of the synthesized polymer. The quantity
      of maleimide on the polymer chain as well as the mucoadhesive properties and
      biocompatibility of the synthesized polymers were also assessed. The results
      revealed that the synthesized MHA-CS demonstrated excellent mucoadhesive
      properties which is superior to CS and Cys-CS. The maleimide content bound to
      synthesized polymer was 466 MUmol per gram of the polymer. The cytotoxicity test
      assured the low toxicity of the synthesized polymer on the normal human gingival
      fibroblast cells. These data support the potential of MHA-CS as a novel material
      for developing mucoadhesive drug delivery system with enhanced mucoadhesive
      properties.

PMID- 30287000
TI  - Plantain flours as potential raw materials for the development of gluten-free
      functional foods.
AB  - Plantain flour (Musa ssp., group AAB, sub-group clone Harton) was modified by
      acetylation, carboxymethylation, methylation, oxidation and phosphation, in order
      to determine which of these modifications produce a material with potential for
      the development of gluten-free products with improved nutritional properties. The
      structural, rheological and nutritional properties of the modified flours were
      investigated. The phosphated plantain flour, cross-linked with sodium
      trimetaphosphate (STMP), had a lower in vitro digestibility rate associated with
      resistant starch (RS) types RS2, RS4 and RS5. This latter was confirmed by the
      formation of the amylose-lipid complex as determined by XRD. All the flours
      tested had a C-type structure with the exception of the methylated plantain flour
      which produced a large quantity of reaction by-product (BaSO4). The phosphated
      plantain flour represents a raw material with great potential for the development
      of gluten-free food (bread and cookie) with functional properties, i.e. health
      benefits.

PMID- 30287001
TI  - Periodate oxidation of xylan-based hemicelluloses and its effect on their thermal
      properties.
AB  - Hemicellulose from pulp mill process water and crop residuals from food
      production often end up in waste streams or burnt for energy contribution. These
      waste products contain valuable biopolymers but lack many attributes needed for
      use in applications such as food and medical or consumer products. This study
      reports on an investigation of the periodate oxidation of hardwood xylan and
      arabinoxylan (AX) from wheat bran to produce materials with new functionalities.
      The study explores how to control the oxidation degree and describes structural
      differences between the two xylan-based polymers. For the xylan samples, the
      oxidation resulted in a lowering of the glass transition temperature (Tg),
      indicating a more flexible chain due to ring-opening of the xylan anhydro-sugar
      units. For the AX samples, the arabinose side-groups were instead oxidized,
      hindering oxidation on part of the xylose units, which resulted in a crosslinked
      network with an unchanged Tg but reduced intrinsic viscosity.

PMID- 30287002
TI  - In vitro and in vivo evaluation of pirfenidone loaded acrylamide grafted pullulan
      poly(vinyl alcohol) interpenetrating polymer networks.
AB  - The aim of present study was to develop controlled release formulation of
      pirfenidone using acrylamide grafted pullulan. Interpenetrating polymer network
      (IPN) microspheres were prepared using acrylamide grafted pullulan and PVA
      utilizing glutaraldehyde assisted water-in-oil emulsion crosslinking method. IPN
      microspheres were characterized by FTIR, solid state 13C NMR and XRD
      spectroscopy. In vitro enzymatic degradation study showed 34.30% degradation
      after 24 h with degradation rate constant of 0.0088 min-1. In vitro
      biocompatibility test showed no changes in cellular morphology and cell adherence
      to microspheres, indicating its biocompatible nature. The release exponent value
      of all formulations was less than 0.45, indicating the release mechanism to be
      Fickian diffusion. Finally, in vivo pharmacokinetic study showed longer Tmax
      (1.16 h) and greater AUC value (10037.76 ng h/mL,) as compared to Pirfenex(r)
      (Tmax = 0.5 h; AUC = 4310.45 ng h/mL,). The results indicated that the prepared
      formulation could successfully control the drug release for prolonged time
      period.

PMID- 30287003
TI  - Effect of chemical modification with citric acid on the physicochemical
      properties and resistant starch formation in different starches.
AB  - Potato, cassava, sweet potato, banana and lentil starches were modified with
      citric acid (CA) with the main objective of enhancing the resistant starch (RS)
      and slowly digestible starch (SDS) fractions and to compare starches of diverse
      botanical origins. The percentage CA substitution of modified starches ranged
      from 3.84 to 15.06 and showed similar type of XRD patterns, but with variation in
      intensity and percentage crystallinity. The peaks around 1705 cm-1 and 1150 cm-1
      in FT-IR spectra of modified starches confirmed the presence of CA group.
      Scanning electron microscopy confirmed that there were no noticeable changes in
      granular structure and morphology. No peaks could be observed in RVA pasting
      profiles of modified starches, confirming cross-linking reaction. The SDS and RS
      were significantly higher in modified starches of all origins and consequently
      there was a lower estimated glyceamic index (EGI). Modified starches were
      associated with lower setback viscosity indicating their lower temperature
      stability.

PMID- 30287004
TI  - Study of the behavior of biodegradable starch/polyvinyl alcohol/rosin blends.
AB  - Biodegradable potato starch/PVA samples containing different concentrations of
      rosin were prepared by melt-mixing in order to study the enhancement of the
      properties of native starch films. Glycerol and polyvinyl alcohol (PVA) are
      commonly used as plasticizers of starch. Their relatively low molecular weight
      (compared with starch) contributes to a good processability. Rosin is a renewable
      product whose incorporation in the starch/PVA matrix induces processing aid and
      reinforcing effects. Its relatively high molecular weight might prevent its
      migration to the surface of the final product. Water content, solubility in
      water, mechanical properties, microstructure and dynamic mechanical analysis of
      the samples were studied. The addition of 8% rosin to starch/PVA blends led to
      tensile strength values higher than 10 MPa and elongation at break values close
      to 2000%, values comparable to those offered by conventional polymers used in
      food packaging, for example LDPE. Furthermore, starch compounds have low cost and
      high biodegradability.

PMID- 30287005
TI  - Efficient removal of Pb(II), Cr(VI) and organic dyes by polydopamine modified
      chitosan aerogels.
AB  - Chitosan is highly suitable for removing metal ions and dyes from water; however,
      the sorption performance, stability and recycling are still critical issues in
      practical applications. Herein, polydopamine-modified-chitosan (CS-PDA) aerogels
      were synthesized through dopamine self-polymerization and glutaraldehyde cross
      linking reactions to enhance the adsorption capacity and acid resistance of
      chitosan. The self-polymerization of dopamine and gelation of chitosan were
      accomplished simultaneously, simplifying the synthesis process of CS-PDA
      aerogels, which is meaningful for the popularization and industrial application
      of adsorbent. CS-PDA exhibited superior adsorption performances in the removal of
      Cr(VI), Pb(II) and organic dyes. Adsorption isotherms and kinetic data were well
      fitted by Langmuir and pseudo-second-order kinetic models. The maximum adsorption
      capacities of CS-PDA for Cr(VI) and Pb(II) were 374.4 and 441.2 mg g-1,
      respectively. After eight cycles, adsorption capacity of CS-PDA showed no obvious
      decline. These superiorities make CS-PDA a promising multifunctional adsorbent
      for the purification of metal ions and dyes.

PMID- 30287006
TI  - Chitosan-gelatin porous scaffold incorporated with Chitosan nanoparticles for
      growth factor delivery in tissue engineering.
AB  - Designing scaffolds capable of mimicking the 3D structure of the extracellular
      matrix (ECM) and deliver signaling factors to affect and control the cell
      response favorably, is of high importance in the field of tissue engineering. As
      polymeric nanoparticles are effective vehicles for delivering growth factors,
      this study aimed to fabricate and characterize a nanocomposite scaffold based on
      chitosan and gelatin, incorporated with chitosan nanoparticles loaded with basic
      fibroblast growth factor (bFGF) and bovine serum albumin (BSA). Nanoparticles,
      prepared by the ionic gelation method, were loaded with BSA-bFGF and introduced
      into chitosan-gelatin scaffolds to enhance their biological properties.
      Structural characterizations and biological assays showed that nanoparticles
      significantly affected the physical properties of the scaffold and could provide
      a sustained release of growth factor to enhance the proliferation of fibroblast
      cells significantly. These results are promising for improving the properties of
      chitosan-gelatin scaffolds in tissue engineering applications, especially where
      the delivery of angiogenic growth factor such as bFGF is needed.

PMID- 30287007
TI  - pH-responsive hyaluronate-anchored extracellular vesicles to promote tumor
      targeted drug delivery.
AB  - pH-Responsive drug vehicles targeting the specific extracellular pH of tumors
      have served as potent tools to overcome the limitation (e.g., low tumor
      seletivity) in antitumor drug delivery system. Here, we describe the advantage of
      pH-responsive extracellular vesicles (HDEA@EVs) containing the hyaluronic acid
      grafted with 3-(diethylamino)propylamine (HDEA) and a model antitumor drug,
      doxorubicin (DOX). We demonstrated their physicochemical characteristics through
      in vitro cell endocytosis, in vitro tumor cell toxicity, in vivo biodistribution,
      and in vivo tumor regression efficacy experiments. Because the HDEA@EVs
      efficiently responded to extracellular tumor pH (pH 6.5) and actively bound to
      CD44 receptors on HCT-116 tumor cells, the EVs selectively inhibited CD44+ tumor
      cell growth in vitro, and CD44+ tumor development in vivo. From these results, we
      conclude that HDEA@EVs can help in designing effective strategies for
      pharmacologic intervention in tumor therapy.

PMID- 30287008
TI  - Chitosan as a substrate for simultaneous surface imprinting of salicylic acid and
      cadmium.
AB  - The present work demonstrates functionalized chitosan as an ecofriendly
      substitute to the conventional costly substrates and monomers for simultaneous
      surface imprinting of salicylic acid (SA) and cadmium (Cd). Dual surface
      imprinted acrylamide functionalized chitosan based polymer (AGDMIP), with higher
      numbers of imprinted sites for SA and Cd was synthesized using acrylamide grafted
      chitosan, epichlorohydrin as crosslinker, Cd as template and 4 hydroxy benzoic
      acid (4HBA) as mimic template (supported by computational modeling). FTIR, SEM,
      XRD, BET surface area and TEM analysis confirmed successful preparation,
      mesoporous nature and surface imprinting of AGDMIP. The adsorption data could be
      fitted into Langmuir isotherm model with the maximum adsorption capacity of 45.77
      mg g-1 (SA) and 53.42 mg g-1 (Cd). Temkin and Intraparticle diffusion models
      confirmed the chemical nature and presence of imprint sites within AGDMIP
      respectively. AGDMIP could be reused for six cycles and exhibited good removal
      efficiency in real samples.

PMID- 30287010
TI  - 'Chitosan in water' as an eco-friendly and efficient catalytic system for
      Knoevenagel condensation reaction.
AB  - The catalytic activity of commercially available chitosan has been investigated
      for the Knoevenagel reaction of ethylacetoacetate (EAA)/dimethylmalonate (DMM)
      with arylaldehydes. Among all the screened solvents, Chitosan performed the best
      in water as reaction medium. Substrate scope was evaluated by using various
      arylaldehydes and it was observed that presence of electron donating groups on
      aldehydes reduce the yields, while electron-withdrawing groups increase the
      yields. In case of the reaction of 4-bromobenzaldeyde with EAA, the lower yield
      of the corresponding product 14 was obtained due to the high stability of imine
      intermediate formed and this postulate was proved by experiments as well as
      theoretical calculations. In case of EAA, the E/Z stereochemistry of the
      corresponding products was assigned based on NOESY experiment.

PMID- 30287009
TI  - Chitosan functionalized poly (epsilon-caprolactone) nanoparticles for
      amphotericin B delivery.
AB  - Amphotericin B (AmB) is a broad-spectrum antifungal drug used in the treatment of
      fungal invasive infections. However, its clinical use has been limited due to its
      side effects and toxicity, especially the nephrotoxicity. Furthermore, AmB
      presents low aqueous solubility, low permeability over the membranes and poor
      stability in the gastric environment, which makes it unavailable to be
      administered by the oral route. In this study, chitosan-coated poly (epsilon
      caprolactone) nanoparticles were developed to provide the oral delivery of AmB
      and reduce its toxicity. Nanoparticles were obtained by nanoprecipitation and
      parameters as particle size, polydispersity index (PDI), zeta potential,
      morphology, in vitro AmB release (in physiological pH and simulated
      gastrointestinal fluids), state of molecular aggregation, cytotoxicity over
      erythrocytes and Vero cells line and in vitro antifungal activity were fully
      investigated. Nanoparticles presented mean size of 318 +/- 35 nm, PDI of 0.24 +/-
      0.02, zeta potential of +36.2 +/- 1.8 mV due to chitosan-coating, and 69% of AmB
      encapsulation. The kinetic release profile of AmB from nanoparticles was of
      second order and diffusion-governed in pH 7.4. The release in the
      gastrointestinal simulated fluids showed that the chitosan-coated PCL
      nanoparticles presented good stability during the time evaluated. AmB was
      released from nanoparticles in a state of low molecular aggregation. Cytotoxicity
      over erythrocytes and Vero cells line revealed that nanoencapsulation
      significantly reduced the AmB-related cytotoxicity (p < 0.05) compared to the
      free drug. In the antifungal activity against Candida parapsilosis strain, the
      MIC of AmB-loaded nanoparticles was 5-fold higher than free AmB, but the strain
      was susceptible to nanostructured AmB. Chitosan-functionalized PCL are potential
      carriers for the oral AmB delivery, reducing its cytotoxicity and maintaining its
      activity.

PMID- 30287011
TI  - Effect of aqueous glycine treatment on the fine structure and dyeing ability of
      cotton.
AB  - Exhaustion dyeing of cotton means a significant proportion of dyestuff is not
      fixed onto the material and is drained out when the dyebath is emptied. This
      waste presents issues for dye houses in terms of remediating water quality and
      the loss of expensive dye chemicals. Work to improve the dyeing ability of cotton
      has been limited to modifying cotton's cellulose structure by, notionally,
      environmentally hazardous treatments, e.g., concentrated caustic soda. Here we
      use a buffered, aqueous glycine treatment to improve the dyeing ability of
      cotton. The treated cotton showed improved dye absorption compared with control
      samples. An investigation of the structure of the treated cotton using Fourier
      Transform Infrared spectroscopy (FTIR) and 13C solid-state nuclear magnetic
      resonance (NMR) showed there was no appreciable change in crystallinity. However,
      there were changes in the chemical structure of the glycine-cellulose complex
      that were related to the pH of the buffered glycine treatment.

PMID- 30287012
TI  - Starch/graphene hydrogels via click chemistry with relevant electrical and
      antibacterial properties.
AB  - Starch-based hydrogels were performed by Diels-Alder cross-linking reactions
      between furan-modified starch and a water soluble bismaleimide, with improving
      conducting properties by using graphene layers as active nanofillers. The
      characterization results demonstrated that the Diels-Alder reaction and the
      corresponding conditions for the hydrogel formation were appropriate. The effect
      of increasing the furan/maleimide ratio on the architecture of the hydrogels and
      on the morphological, rheological and swelling properties were thoroughly
      evaluated. Effective network structure was obtained by increasing the cross
      linker content leading to decreasing pore size and increasing storage modulus
      value of the final material. It was shown that the swelling behavior of hydrogels
      was mainly governed by the hydrophilic character of bismaleimide. Graphene
      nanosheets were added for the synthesis of nanocomposite hydrogel and it was
      characterized in terms of rheological properties, electrical conductivity and
      antimicrobial activity. The nanocomposite hydrogel presented enhanced mechanical
      performance, antimicrobial activity and increased conductivity values, up to a
      decade, indicating that conductive and active hydrogels could be satisfactory
      obtained, for a large range of potential applications such as biomed.

PMID- 30287013
TI  - Sulfonated and sulfated chitosan derivatives for biomedical applications: A
      review.
AB  - From 20th century, chitosan, a natural polysaccharide, has received much
      attention for use in biomedical applications thanks to its remarkable properties,
      such as biodegradability, biocompatibility, hemostasis and antibacterial
      activity. Over the last decades, many researchers have attempted to generate new
      chitosan derivatives-based biomaterials though chemical modifications, especially
      through sulfonation or sulfation reactions in order to tailor the physicochemical
      and biochemical properties. Due to the presence of residual amino groups, the
      generated polyampholytic derivatives are characterized by convenient biological
      properties, such as antioxidation, antiviral activity, anticoagulation and bone
      regeneration, expanding their application scope. This paper provides an overview
      of the strategies used to chemically modify chitosan by introduction of sulfonate
      groups on chitosan backbone, focusing on various sulfonating or sulfating agents
      used and substitution regioselectivity, and highlights their applications in
      biomedical field.

PMID- 30287014
TI  - Preparation, characterization and functional evaluation of chitosan-based films
      with zein coatings produced by cold plasma.
AB  - Chitosan-based films with zein coatings were prepared in order to modify the drug
      release properties. The adhesion of zein layers to the films was ensured via a
      cold plasma treatment. Using ciprofloxacin hydrochloride as model, the effect of
      cold plasma on the functional properties and structures was evaluated. The
      results suggest that the encapsulation efficiency, chemical composition and
      crystal type of ciprofloxacin hydrochloride in chitosan/drug films were not
      altered by cold plasma treatment, while the wettability and surface free energy
      displayed a notable increase. After being coated with zein, the chitosan
      interacted with the zein through hydrogen bonding and electrostatic interactions.
      The burst release phenomenon of the chitosan/drug films was prevented by the zein
      coating. Furthermore, the plasma treatment provided the coated film with a slower
      release rate within 24 h, from 72.8% to 49.3%. The enhanced coating thickness and
      the more compact interface structure were responsible for this improvement.

PMID- 30287015
TI  - Modification of chitin structure with tailored ionic liquids.
AB  - Chitin, poly N-acetylglucosamine, has a great potential for use on an industrial
      scale as an enzyme carrier but it has an unfavorable particle structure that can
      be modified using ionic liquids (ILs). Several ionic liquids were investigated
      that have the same substituents on the ring (methyl- and propyl-) but differed in
      the type of cationic ring (pyrrolidinium, piperidinium, and piperazinium).
      Organic acid ions (acetic and lactic) were used as counter ions. 1-ethyl-3-methyl
      imidazolium acetate and 1-ethyl-3-methyl-imidazolium lactate were used as a
      reference. The results confirm that the chitin particle structure or size, or
      both, simultaneously changes if chitin is dissolved in an IL and then
      precipitated. Organic acid anions and short substituents on the cationic ring of
      ILs influenced particle modification substantially, whereas the type of ring
      played a minor role. Additionally, the ionic liquids [MPpyrr][OAc], [MPpip][OAc]
      and [DMPpz][OAc] could be reused up to at least 4 times without losing their
      ability to dissolve chitin.

PMID- 30287016
TI  - Water dynamics in silanized hydroxypropyl methylcellulose based hydrogels
      designed for tissue engineering.
AB  - Silanized hydroxypropyl methylcellulose based hydrogels were developed for
      cartilage and intervertebral disc tissue engineering. Herein, study of dynamics
      of confined water showed two different populations, identified as hydration and
      bulk-like water. The diffusion coefficient showed that bulk-like water diffuses
      over distances ~10 MUm without being affected by the hydrogel matrix. Addition of
      silica nanofibers leads to improved mechanical properties and enhanced diffusion
      coefficient. Good diffusion within hydrogels is essential for the application.

PMID- 30287017
TI  - A novel, green, low-cost chitosan-starch hydrogel as potential delivery system
      for plant growth-promoting bacteria.
AB  - The study examines the use of macrobeads for the controlled-release of bacteria.
      Macrobeads were prepared by an easy dripping-technique using 20/80 wt/wt chitosan
      starch blends and sodium tripolyphosphate as cross-linking agent. The resulting
      polymeric matrix was examined by SEM, XRD, TGA, and solid-RMN. The swelling
      equilibrium, thermal behaviour, crystallinity, and size of macrobeads were
      affected by the autoclave-sterilization. The diameter of the sterilized xerogel
      was c.a. 1.6 mm. The results suggested that ionotropic-gelation and
      neutralization were the mechanisms underlying hydrogel formation. Plant growth
      promoting bacteria (PGPB) were loaded into macrobeads separately or co
      inoculated. Bacteria loaded macrobeads were dried and stored. Bacteria survived
      at least 12 months in orders of 109 CFU of A. brasilense/g and 108 CFU of P.
      fluorescens/g. Bacterial release in sterile saline solution tended to a super
      Case-II transport mechanism. Polymeric-matrix release efficiently both PGPB in
      natural soils, which uncovers their potential for the formulation of novel and
      improved biofertilizers.

PMID- 30287018
TI  - Nanocellulose and chitosan based films as low cost, green piezoelectric
      materials.
AB  - Nanocellulose and chitosan have recently started to get attention as
      environmentally friendly piezoelectric materials for sensor and energy harvesting
      applications. Conversely, current commercially available flexible piezoelectric
      films made of for example polyvinylidene difluoride (PVDF) are relatively
      expensive and made from non-renewable materials. We measured the piezoelectric
      responses (2-8 pC/N) for solvent casted films based on nanocellulose,
      microcrystalline chitosan and their blends. In addition, the tensile properties
      of the piezoelectric films were characterized to find out if chitosan could be
      used to enhance the flexibility of the brittle nanocellulose films. Based on the
      results, plain chitosan is an interesting piezoelectric material itself. In
      addition, blending nanocellulose and chitosan could be a potential method for
      tailoring the properties of solvent casted low cost, green piezoelectric films.

PMID- 30287019
TI  - Natural polymer konjac glucomannan mediated assembly of graphene oxide as
      versatile sponges for water pollution control.
AB  - Three-dimensional network structure of konjac glucomannan/graphene oxide (KGM/GO)
      sponges was successfully prepared by ice template method. The KGM/GO sponges was
      rich in functional groups, negatively charged under pH 2 to 10. Batch adsorption
      experiment was conducted to investigate the adsorption performance of the as
      prepared KGM/GO sponges for organic dye (malachite green (MG)) and radionuclide
      (uranium U(VI)). The results showed that the maximum adsorption capacities of
      KGM/GO sponges were 266.97, 189.96 mg/g for U(VI) and MG, respectively. Moreover,
      the KGM/GO sponges exhibited an excellent selectivity for capturing U(VI) in
      multi-ion system. The adsorption process was fitted better to pseudo-second order
      model, while adsorption isotherms for these pollutants were well matched up to
      Langmuir models. In addition, KGM/GO sponges can be easily separated from the
      aqueous solution and could be effectively reused for 5 times without obvious loss
      in adsorption performance. The advantages of eco-friendliness, low cost, simple
      preparation process, controllable shape and size, as well as high adsorption
      capacities for MG and U(VI), suggested that KGM/GO sponges promising in water
      pollution control.

PMID- 30287020
TI  - Distinct polymer extraction and cellulose DP reduction for complete cellulose
      hydrolysis under mild chemical pretreatments in sugarcane.
AB  - In this study, liquid hot water (LHW) and chemical (H2SO4, NaOH, CaO)
      pretreatments were performed in Saccharum species including sugarcane bagasse. In
      comparison, the LHW and CaO pretreatments significantly enhanced biomass
      enzymatic hydrolysis, leading to much high bioethanol yield obtained at 19% (%
      dry matter) with an almost complete hexoses-ethanol conversion in the desirable
      So5 bagasse sample. Despite the LHW and CaO are distinctive for extracting
      hemicellulose and lignin, both pretreatments largely reduced cellulose degree of
      polymerization for enhanced lignocellulose enzymatic saccharification. Further
      chemical analysis indicated that the pretreated So5 sample had much lower
      cellulose crystalline index, hemicellulosic Xyl/Ara and lignin S/H ratio than
      those of other biomass samples, which explained that the So5 had the highest
      bioethanol yield among Saccharum species. Therefore, a mechanism model was
      proposed to elucidate how mild pretreatments could enhance biomass enzymatic
      saccharification for a high bioethanol production in the desirable sugarcane
      bagasse.

PMID- 30287021
TI  - Fabrication and characterization of Gum arabic-cl-poly(acrylamide) nanohydrogel
      for effective adsorption of crystal violet dye.
AB  - Natural biopolymers are better adsorbents due to better functionality, surface
      area, bio-compatibility and ease of procurement. The gum arabic in natural
      biopolymer derived from Acacia Arabic species. In the present work a novel
      nanohydrogel of gum arabic with acrylamide has been fabricated using microwave
      synthesis for adsorption of noxious crystal violet dye from aqueous medium. The
      prepared gum arabic-cl-poly(acrylamide) nanohydrogel (GA-cl-poly(AAm)) NHG was
      characterized by numerous techniques including SEM, XRD, TEM and FTIR. The GA-cl
      poly(AAm) NHG showed promising adsorption ability for crystal violet dye. The
      effect of various adsorption factors such as concentration of GA-cl-poly(AAm) NHG
      and crystal violet, pH, temperature and time has been studied and reported. For
      understanding the adsorption mechanism three models Langmuir, Freundlich and
      Temkin were applied to adsorption data The kinetics and thermodynamics of
      adsorption were also investigated The adsorption capacity of crystal violet onto
      GA-cl-poly(AAm) NHG according to Langmuir model is found to be 90.90 mg/g.

PMID- 30287022
TI  - Crosslinking of agar by diisocyanates.
AB  - In the present study, crosslinking of agar using diisocyanate (DI) was
      demonstrated to limit the high water absorption property of agar. In addition,
      the efficacy of aromatic diisocyanate, DDI (4, 4 diphenyl diisocyanate) and
      aliphatic diisocyanate, HDI (1, 6 hexamethylene diisocyanate) on crosslinked agar
      properties was compared. The water uptake was successfully reduced by
      crosslinking and its minimum values observed for DDI and HDI crosslinked agar was
      33.6% and 43.6%, respectively in comparison to agar (206%). The maximum tensile
      strength was observed for DDI crosslinked agar (45.3 MPa) which was higher than
      HDI crosslinked agar (30.6 MPa) and agar (31.7 MPa). The aromatic diisocyanates
      crosslinked agar showed better thermal resistance at higher temperature. It was
      observed that aromatic diisocyanate crosslinked agar more effectively than the
      aliphatic diisocyanate due to the higher reactivity. The crosslinked agar samples
      were hemocompatible and show non-toxic nature for cell proliferation.

PMID- 30287023
TI  - Chemical characteristics, antioxidant capacities and hepatoprotection of
      polysaccharides from pomegranate peel.
AB  - This proposed work aimed to investigate the chemical characteristic, antioxidant
      capacities and hepatoprotection effect of pomegranate peel polysaccharides (PPP)
      on CCl4-induced oxidative damage in mice. PPP was identified as the acidic
      heteropolysaccharides by HPLC methods. In vitro test showed that PPP had
      excellent reducing power and scavenging effects against free radicals.
      Administration of PPP (50, 100 and 200 mg/kg.bw) in mice before the injection of
      CCl4 could observably antagonize the increased serum alanine aminotransferase,
      aspartate aminotransferase, alkaline phosphatase and hepatic malonaldehyde level
      in CCl4-induced mice, especially administrated with 200 mg/kg.bw of PPP. Hepatic
      enzymatic activities of total superoxide dismutase, glutathione peroxidase,
      catalase and non-enzymatic activity of glutathione were markedly increased at
      high dosage of PPP, respectively. In addition, histopathological observation of
      liver further proved these biochemical characteristics. Therefore, it can be
      concluded that PPP exhibits strong protective effects against CCl4-induced liver
      injury in mice.

PMID- 30287024
TI  - Effects of weak-light stress during grain filling on the physicochemical
      properties of normal maize starch.
AB  - The grain development of normal maize in Southern China is affected by decreases
      in sunlight intensity over the period of mid-June to mid-July. This study
      examined the starch structure and function of four normal maize varieties that
      had been exposed to weak-light stress (50% light deprivation; ambient light
      conditions served as the control) during grain filling. In all tested varieties,
      light deprivation decreased the contents of starch and amylose, and increased the
      size of starch granules and the proportion of long chains in amylopectin. Shading
      increased the relative crystallinity and ordered-to-amorphous ratio of starch.
      Shading decreased the gelatinization and retrogradation enthalpies and pasting
      and gelatinization temperatures of starches but increased retrogradation
      percentage and pasting viscosities. In conclusion, weak-light stress during grain
      filling increases starch viscosity and retrogradation tendency and decreases
      thermal stability by reducing amylose content, increasing the sizes of starch
      granules and the proportion of long chains in amylopectin, and improving the
      relative crystallinity.

PMID- 30287025
TI  - Modified cellulose by polyethyleneimine and ethylenediamine with induced Cu(II)
      and Pb(II) adsorption potentialities.
AB  - In order to synthesize adsorbent that can effectively absorb heavy metals in a
      simple and economical way, this study described the fabrication of adsorbents
      based on cellulose acetate (CA). CA modified first by polyethyleneimine grafting
      (CAP) and then by ethylenediamine (CAPE) for enhancing Cu(II) and Pb(II) removal
      from water. The physico-chemical properties of the modified celluloses were
      analyzed. It was found that the adsorption functional groups (amino groups) were
      successfully grafted on cellulose and CAP converted from semi-crystalline to
      cellulose II after enhancement of ethylenediamine (EDA). Adsorption isotherm
      results showed that the Cu(II) and Pb(II) removal efficiency by CAPE was
      significantly higher than that by CAP, and CAP showed a higher adsorption
      capacity of Cu(II) and Pb(II) than CA, of which the adsorption isotherm modeled
      with Langmuir isotherms well. The adsorption capacity can significantly be
      affected by ionic strength and humic acid. Fourier transform infrared (FTIR)
      spectroscopy and X-ray photoelectron spectroscopy (XPS) results demonstrated the
      complexation between amino groups and Cu(II)/Pb(II) played an important role for
      adsorption onto CAPE.

PMID- 30287026
TI  - Layer-by-layer-assembled chitosan/phosphorylated cellulose nanofibrils as a bio
      based and flame protecting nano-exoskeleton on PU foams.
AB  - The layer-by-layer (LbL) assembly of chitosan (CH) and phosphorylated cellulose
      nanofibrils (P-CNF) is presented as a novel, sustainable and efficient fire
      protection system for polyurethane foams. The assembly yields a linearly growing
      coating where P-CNF is the main component and is embedded in a continuous CH
      matrix. This CH/P-CNF system homogenously coats the complex 3D structure of the
      foam producing a nano-exoskeleton that displays excellent mechanical properties
      increasing the modulus of the foam while maintaining its ability of being
      cyclically deformed. During combustion the CH/P-CNF exoskeleton efficiently
      prevents foam collapse and suppresses melt dripping while reducing the heat
      release rate peak by 31% with only 8% of added weight. The coating behavior
      during combustion is investigated and correlated to the observed performances.
      Physical and chemical mechanisms are identified and related to the unique
      composition and structure of the coating imparted by the LbL assembly.

PMID- 30287027
TI  - The three dimensional cues-integrated-biomaterial potentiates differentiation of
      human mesenchymal stem cells.
AB  - Alginate (Alg) hydrogels, the most popular natural biomaterials, mimic the
      extracellular matrix (ECM) microenvironment and offer potential biomedical
      applications. Despite their excellent properties such as biocompatibility,
      hydrophilicity and ionic crosslinking, the absence of an intrinsic cell adhesion
      domain lessens their cell-carrier applications in tissue engineering. Herein, we
      suggest a three-dimensional (3D) cell culture system by integrating Alg hydrogel
      and fibroblast-derived matrix (FDM). FDM including cell-adhesion motifs,
      signaling, and physico-mechanical cues is prepared by the decellularization
      process by avoiding unfavorable chemical reactions. This cues-integrated
      biomaterials (CiB) 3D platform shows increased cell viability, proliferation,
      chondrogenic and osteogenic differentiation of human bone-marrow-derived
      mesenchymal stem cells (hMSCs) in situ. The results show that the Alg/FDM
      hydrogel (CiB) matrix provides an excellent microenvironment for cell adhesion
      and can control the differentiation of hMSCs into specific lineages. Thus, these
      results suggest the potential applications of the Alg/FDM hydrogel matrix as a
      viable 3D culture system for tissue regeneration.

PMID- 30287028
TI  - Extraction optimization of pectin from cocoa pod husks (Theobroma cacao L.) with
      ascorbic acid using response surface methodology.
AB  - Cocoa husks were used as the source for the pectin extraction by sugar acid
      treatment. A full factorial design was applied to screen the independent
      variables influencing the yield and uronic acid content. Followed by response
      surface methodology (RSM) was conducted using central composite design to
      optimize the extraction conditions. The optimized extraction condition was
      denoted as pH 2.5/95  degrees C/45 min. The yield and the uronic acid content of
      the extracted pectin was determined as 4.2 +/- 0.12% and 74.5 +/- 0.3%
      respectively. The extracted pectin was proved to be low methoxy pectin (LM
      pectin) with an 8.1% degree of esterification (DE). The pectin solutions showed
      shear thinning behaviour which was explicated by Williamson model. This work
      promotes environmentally friendly technology for pectin isolation.

PMID- 30287029
TI  - MWCNT-coated cellulose nanopapers: Droplet-coating, process factors, and
      electrical conductivity performance.
AB  - Electrically conductive cellulose nanopapers (EC-CNPaps) were fabricated by the
      droplet-coating of multiwall carbon nanotubes (MWCNTs) on cellulose nanopapers
      (CNPaps), and the effects of the process factors on the electrical conductivity
      of EC-CNPaps were investigated. The type of CNPaps (made of softwood
      nanofibrillated cellulose or bacterial cellulose nanofibres), the drying methods
      of CNPaps (air drying, freeze drying, and oven drying), the applied method for
      the stabilisation and the concentration of MWCNT-water solutions, and the droplet
      coating temperatures (~23  degrees C and ~60  degrees C) were the examined
      variable factors. Overall, the oven-dried nanofibrillated cellulose paper as a
      substrate, 0.1 wt. % of the gum Arabic stabilised MWCNT-water solution ink, and
      the droplet coating at 60  degrees C were introduced as the optimum conditions of
      the examined process factors in this study.

PMID- 30287030
TI  - Hyaluronic acid-functionalized half-generation of sectorial dendrimers for
      anticancer drug delivery and enhanced biocompatibility.
AB  - Biocompatible, pH-sensitive and charge-conversion micelles derived from
      hyaluronic acid (HA), poly(lactide) (PLA) and half-generation of sectorial
      poly(amidoamine) dendrimers (sPA G4.5) were designed and fabricated to target
      delivery of docetaxel (DTX) to cancer cells. The novel micelles (HA-PALA-DTX)
      possessed stability against rat plasma and were capable of reversing surface zeta
      potential under acidic conditions in the presence of HAase. Moreover, the blank
      micelles demonstrated satisfactory biocompatibility and viability for biomedical
      applications. A cellular internalization experiment indicated that HA played an
      important role in increasing intracellular accumulation of DTX delivered by the
      micelles. Compared to Taxotere(r) and PALA-DTX, HA-PALA-DTX showed an enhanced
      anticancer activity in vivo, with a tumor growth inhibition rate of 72.32 +/-
      5.22%. Overall, the functionalized micelles could be utilized as an alternative
      carrier for effective targeted delivery of anticancer agents to improve
      therapeutic efficacy and minimize adverse effects.

PMID- 30287031
TI  - Electroactive polyaniline/silica hybrid gels: Controllable sol-gel transition
      adjusted by chitosan derivatives.
AB  - In this study, the electroactive hybrid gels with controllable sol-gel process
      were fabricated based on the water soluble polyaniline complex and water soluble
      silica precursor. beta-cyclodextrin grafted on chitosan (CSCD) acted as a
      template, a new route for the synthesis of water soluble polyaniline complex
      (PA@CSCD) was designed by in-situ polymerization. Then, the hybrid silica gels
      without severe shrinkage were prepared by mixing PA@CSCD complex with water
      soluble precursor (tetrakis(2-hydroxyethyl)orthosilicates, THEOS). By dynamic
      rheological measurements, it was found that PA@CSCD complex could trigger and
      accelerate the sol-gel transition of the silica precursor. The gelation time
      could be largely shortened with the increase of PA@CSCD complex amount. By SEM
      observation, the PA@CSCD complex could be well compatible with the silica matrix.
      Moreover, the hybrid gels showed the good redox electroactivity, which could be
      successfully applied in a HRP-based biosensor.

PMID- 30287032
TI  - Influence of cations on texture, compressive elastic modulus, sol-gel transition
      and freeze-thaw properties of kappa-carrageenan gel.
AB  - The influences of 4 mono- and di-valent cations (K+, Na+, Mg2+ and Ca2+) on the
      mechanical, sol-gel transition and freeze-thaw properties of kappa-carrageenan
      gel were investigated. Texture profile analysis results demonstrated that the
      texture behavior of gelatinized kappa-carrageenan was obviously influenced by the
      cation types and concentrations and the influence of K+ was the greatest. The
      gelling temperature (Tg) of kappa-carrageenan gel showed a positive correlation
      with cation concentrations and the influence of K+ was still the largest.
      However, the viscosities of kappa-carrageenan gels evoked by divalent cations
      were higher than monovalent cations. Furthermore, cations reduced freeze-thaw
      stability of kappa-carrageenan gels and followed the same influence tendency as
      viscosities. It was proposed that divalent cations form direct crosslinking
      between kappa-carrageenan helices while monovalent cations only bind single
      sulphate groups on kappa-carrageenan molecules. There were more junction zones in
      divalent cations invoked gels. Furthermore, K+ and Ca2+ cations showed apparent
      synergistic effect in the research.

PMID- 30287033
TI  - Chemical identification of a sulfated glucan from Antrodia cinnamomea and its
      anti-cancer functions via inhibition of EGFR and mTOR activity.
AB  - Antrodia cinnamomea is a polyporaceous medicinal and native fungus in Taiwan. In
      this study, we found that AC-SPS-F3, a sulfated glucan from A. cinnamomea,
      reduced lung cancer cell viability via inhibition of EGFR and mTOR activity. The
      co-administration of AC-SPS-F3 and cisplatin synergistically inhibited lung
      cancer cell viability. We identified AC-SPS-F3 was a sulfated beta-(1->4)-d
      glucan with two long 1,6-branches in each repeat unit. The FT-IR absorption at
      1341 cm-1 and 887 cm-1 confirmed the existence of sulfates. The proposed repeat
      unit of AC-SPS-F3, including the types of main skeleton and side chains, as well
      as the position of the minor galactopyranosyl and mannopyranosyl residues, were
      proposed according to the 1D and 2D NMR spectra, shown as follows: The features
      for the proposed repeat unit of AC-SPS-F3 included two long beta-(1->6)-Glcp
      branches, a very high ratio of sulfate substitution, and partial 2-O and 4-O
      substituents evenly distributed on the beta-(1->6)-Glcp branches. The present
      study is first to characterize the highly branched sulfated polysaccharides and
      elucidates its anti-cancer functions.

PMID- 30287034
TI  - Facile strategy involving low-temperature chemical cross-linking to enhance the
      physical and biological properties of hyaluronic acid hydrogel.
AB  - Here, we present a novel strategy to fabricate hyaluronic acid (HA) hydrogels
      with excellent physical and biological properties. The cross-linking of HA
      hydrogel by butanediol diglycidyle ether (BDDE) was characterized under different
      reaction temperatures, and the resulting physical properties (i.e., the storage
      modulus and swelling ratio) were measured. The ratio between the cross-linking
      rate (a strengthening effect) and the hydrolysis rate (a weakening effect) was
      much greater with lower cross-linking temperatures after sufficient cross-linking
      time, resulting in a noticeably higher storage modulus. As the cross-linking
      temperature decreased, the formed HA hydrogel structure became denser with
      smaller pores. Moreover, the introduction of low-temperature HA cross-linking
      strategy also resulted in an enhanced several important characteristics of HA
      hydrogels including its enzymatic resistivity and its ability to elicit a
      cellular response. These results indicate the performance of HA hydrogels can be
      markedly enhanced without further additives or modifications, which is expected
      to contribute to the advancement of applications of HA hydrogels in all
      industrial fields.

PMID- 30287035
TI  - An arabinogalactan-glycoconjugate from Genipa americana leaves present
      anticoagulant, antiplatelet and antithrombotic effects.
AB  - Glycoconjugates extracted from Genipa americana leaves (PE-Ga) were separated
      into two fractions, denominated as PFI and PFII (total carbohydrate: 23
      36%/uronic acid: 9-30%; protein:4-5%; polyphenols:0.776-0.812 mg/g), mainly
      composed by arabinose, galactose and uronic acid and presenting high (PFI) and
      low (PFII) molecular weight (based on polyacrylamide electrophoresis gel and gel
      permeation chromatography). Uronic acid was also detected by FT-IR (wavenumbers:
      1410 and 1333 cm-1) and NMR (alpha-GalpA). Deproteinization of glycoconjugates
      showed reduced protein and polyphenol levels with loss of its biological effects.
      PE-Ga and PFII prolonged clotting time-aPTT (3.6 and 1.8x), while PE-Ga and PFI
      inhibited by 48% (100 MUg/MUL) the ADP-induced platelet aggregation. In vivo,
      these glycoconjugates at 1 mg/kg inhibited (37-53%) venous thrombus formation
      (4.7 +/- 0.1 mg) and increased bleeding time (PE-Ga and PFI:3.0x; PFII:1.7x vs.
      PBS:906 +/- 16.7 s). In conclusion, the arabinogalactan-rich glycoconjugate of G.
      americana leaves, containing uronic acid, present antiplatelet, anticoagulant
      (intrinsic/common pathway) and antithrombotic effects, with low hemorrhagic risk.

PMID- 30287036
TI  - Investigation of interactions between the marine GY785 exopolysaccharide and
      transforming growth factor-beta1 by atomic force microscopy.
AB  - Sulfated polysaccharides, such as glycosaminoglycans (GAG) regulate various
      biological activities through their interactions with growth factors.
      Investigating these interactions becomes the key to understand the structure
      function relationship of GAG. Highly sulfated derivatives prepared from the
      marine GY785 exopolysaccharide (EPS) produced by the deep-sea hydrothermal vent
      bacterium Alteromonas infernus have previously shown to stimulate the
      chondrogenic differentiation of mesenchymal stem cells in the presence of
      Transforming Growth Factor-beta1 (TGF-beta1). Here, the interactions between the
      GAG-mimetic GY785 EPS derivatives and TGF-beta1 were investigated by Atomic Force
      Microscopy (AFM). The affinity between slightly sulfated or highly sulfated
      derivatives and TGF-beta1 was explored by AFM imaging and single-molecule force
      spectroscopy experiments. The number of measured interactions and the interaction
      strength were both higher for highly sulfated derivative compared to the slightly
      sulfated one. These results clearly emphasize the involvement of sulfate groups
      in the protein binding and open new ways to tune cellular processes by designing
      macromolecules with adjustable sulfate charge density.

PMID- 30287037
TI  - A recoverable dendritic polyamidoamine immobilized TEMPO for efficient catalytic
      oxidation of cellulose.
AB  - Polyamidoamine (PAMAM) dendrimers of G1.0 and 2.0 were synthesized by the
      repeated Michael addition and ester aminolysis of ethylenediamine and methyl
      acrylate. Through the reductive amination reaction of primary amines in PAMAM and
      carbonyl groups in 4-oxo-2,2,6,6-tetramethylpiperidine-1-oxyl (4-oxo-TEMPO), the
      water-soluble PAMAM immobilized TEMPO (PAMAM-TEMPO) was successfully prepared.
      The obtained PAMAM-TEMPO was characterized by Fourier transform infrared
      spectroscopy (FT-IR) and ultraviolet-visible spectrophotometer (UV-vis). PAMAM
      TEMPO was used as catalyst instead of free TEMPO for selective catalytic
      oxidation of primary hydroxyl groups in cellulose with water as reaction medium.
      The results showed that the catalytic performance of G1.0 PAMAM-TEMPO with 28.8%
      TEMPO loading was equivalent to free TEMPO. After salting out the supernatant of
      oxidation mixture, PAMAM-TEMPO was recovered by extraction with N,N
      dimethylformamide and reused for further oxidation cycles. No significant
      reduction in catalytic performance was found after 4 oxidation cycles. The
      recovery of PAMAM-TEMPO after each cycle was about 90%. By sonication of oxidized
      cellulose obtained with G1.0 PAMAM-TEMPO as catalyst, the individualized
      cellulose nanofibers with approximately 10 nm in diameter were successfully
      prepared. This is the first report on the use of immobilized TEMPO catalysts
      comparable to the performance of free TEMPO to oxidize cellulose in water.

PMID- 30287038
TI  - Superhydrophobicity, UV protection and oil/water separation properties of fly
      ash/Trimethoxy(octadecyl)silane coated cotton fabrics.
AB  - The presented study proposed simple and low-cost approach for improvement in UV
      protection and superhydrophobic properties of cotton fabrics by coating of
      mechanically activated fly ash particles. The maximum UV blocking was observed
      for 3 wt% fly ash, where UV transmittance decreased from 14.19% of untreated
      fabric to 0.11% of coated fabric. After subsequent treatment of
      Trimethoxy(octadecyl)silane (OTMS) on fly ash coated fabrics, the water contact
      angle was increased to 143 degrees , 147 degrees  and 153 degrees  for fly ash
      concentration of 1, 2 and 3 wt% respectively. From Cassie-Baxter theories, the
      unwetted fraction of air pockets were estimated to be 43%, 55% and 67%
      respectively for 1, 2 and 3 wt% of fly ash particles. Furthermore, the coated
      fabrics showed great potentials for separation of floating oil layer, underwater
      oil droplet or oil/water mixture. The separation efficiency of 98%, 96%, 97% and
      95% was obtained for selected model oils toluene, n-hexane, chloroform and petro
      ether, respectively.

PMID- 30287039
TI  - Ganoderma atrum polysaccharide improves doxorubicin-induced cardiotoxicity in
      mice by regulation of apoptotic pathway in mitochondria.
AB  - The present study aimed to determine the cardioprotective effect of Ganoderma
      atrum polysaccharide (PSG-1) in doxorubicin (DOX)-treated mice and its underlying
      mechanism. Results indicated that PSG-1 treatment significantly alleviated DOX
      induced myocardial damage via attenuating apoptosis and maintaining the structure
      of myocardial mitochondria. Meanwhile, PSG-1-evoked cardioprotection was
      associated with an increase of manganese superoxide dismutase activity and
      decrease of caspases activities. Moreover, administration of PSG-1 suppressed DOX
      induced mitochondrial disorders, which was evidenced by reducing reactive oxygen
      species, elevating mitochondrial membrane potential and inhibiting the opening of
      mitochondrial permeability transition pore. PSG-1 was also found to reduce the
      release of cytochrome c from mitochondria to cytoplasm in mice subjected to DOX.
      Finally, our findings have provided comprehensive evidence for the
      cardioprotective effects of PSG-1 via reduction of apoptosis mediated by
      modification of the mitochondrial intrinsic apoptotic pathway, indicating that
      PSG-1 could be developed as an effective therapeutic strategy to prevent DOX
      induced cardiotoxicity in clinical settings.

PMID- 30287040
TI  - Green functionalization of cellulose nanocrystals for application in reinforced
      poly(methyl methacrylate) nanocomposites.
AB  - Cellulose nanocrystals (CNC) were carboxylated through an organic solvent free
      esterification method using l-malic acid (MA) to improve performance of
      transparent poly(methyl methacrylate) (PMMA) nanocomposites. A series of CNC
      carboxylated with a degree-of-substitution (DS) of 0, 0.035, and 0.20 were
      obtained. The presence of grafted carboxyl groups was characterized by Fourier
      transform infrared (FT-IR) spectroscopy and 13C NMR analysis, meanwhile effects
      of content and DS of CNC on the structure, thermal, mechanical, and optical
      transparency properties of the nanocomposites were assessed. The results
      indicated that the homogeneous dispersion of CNC and a favorable PMMA-CNC
      interface were necessary to enhance the properties of nanocomposites. Facilitated
      through hydrogen bonding interactions, the resulting films demonstrated that a
      low percentage loading of CNC with high DS worked as effective reinforcing
      agents, producing stronger and tougher films than neat PMMA films, with an
      improved thermal stability and retention of good transparency.

PMID- 30287041
TI  - Bioperformance of chitosan/fluoride-doped diopside nanocomposite coatings
      deposited on medical stainless steel.
AB  - This work focuses on the structure, bioactivity, corrosion, and biocompatibility
      characteristics of chitosan-matrix composites reinforced with various amounts of
      fluoride-doped diopside nanoparticles (at 20, 40, 60, and 80 wt%) deposited on
      stainless steel 316 L. Bioactivity studies reveal that the presence of the
      nanoparticles in the coatings induces apatite-forming ability to the surfaces.
      Based on electrochemical impedance spectroscopy and polarization experiments, the
      in vitro corrosion resistance of the substrate was enhanced by increasing the
      level of the nanoparticles in the coating. The sample containing 60% of the
      nanoparticles presented the highest osteoblast-like MG63 cell viability, in
      comparison to the other prepared and even control samples. Also, the cell
      attachment on the surfaces was improved with increasing the amount of the
      nanoparticles in the coatings. It is eventually concluded that the application of
      chitosan/fluoride-doped diopside nanocomposite coatings improves the
      bioperformance of metallic implants.

PMID- 30287042
TI  - Porous chitosan microspheres as microcarriers for 3D cell culture.
AB  - Highly porous chitosan microspheres (CSM) were prepared through emulsion-based
      thermally induced phase separation (TIPS) without using toxic crosslinkers and
      chemical porogenic agents other than ice. The CSM had an average diameter of ~150
      MUm with interconnected pores varying from 20~50 MUm in size. Due to their
      excellent biocompatibility and unique porous structure, high-performance
      hepatocyte culture in three-dimensional (3D) space was achieved using the CSM as
      microcarriers, as cell growth also took place within the internal pores of the
      CSM, besides their external surface, and multidirectional cell-cell interactions
      were observed. Enhanced cellular activity and functions were obtained with the
      CSM microcarriers as compared with 2D cell culture. It is believed that these CSM
      microcarriers provide a promising platform for 3D cell culture in vitro.

PMID- 30287043
TI  - Surfactant-free emulsion Pickering polymerization stabilized by aldehyde
      functionalized cellulose nanocrystals.
AB  - Aldehyde-functionalized cellulose nanocrystals (CN) with two aldehyde contents
      were produced by periodate oxidation and gentle sonication. The aldehyde
      functionalized CNCs were shown to be an effective stabilizer in the Pickering
      emulsion polymerization of acrylate monomers using potassium persulfate
      (KPS)/metabisulfite redox initiation system at 50  degrees C without any added
      surfactant. The effect of CNC content on the particle size, zeta-potential,
      colloidal stability and film properties were discussed. CNCs with the highest
      aldehyde content impart better colloidal stability to the polymer dispersion and
      lower particle size. The stabilization process was explained by the reaction of
      bisulfite with aldehyde groups borne by CNC, forming an adduct that contributes
      to the initiation of the polymerization and nucleation of polymer particles. This
      favors the effective attachment of CNCs onto the polymer particle, which is
      prerequisite for the effective Pickering stabilization process. The optical and
      mechanical properties of the nanocomposite films obtained by simple casting of
      the polymer dispersion and water evaporation were also investigated by
      transmittance and dynamic mechanical analysis (DMA). Better transparency was
      observed for films prepared in the presence of CNCs with the highest aldehyde
      content, while a reverse trend was noted for the mechanical properties.

PMID- 30287044
TI  - Hyaluronic acid based nanocrystals hydrogels for enhanced topical delivery of
      drug: A case study.
AB  - The objective of this study is to use a carbohydrate polymer hyaluronic acid
      (HLA) as matrix to design novel transdermal nanogel loading poorly soluble drug
      nanocrystals. Baicalin nanocrystals (BCA-NC) were prepared by coupling
      homogenization technology and spray-drying technology. The morphology, the
      rheological behavior and transdermal permeation studies of HLA based BCA-NC-gel
      were evaluated. The results demonstrated that the BCA-NC could be successfully
      prepared in terms of trehalose after spray-drying. The trehalose could prevent
      the aggregation of BCA-NC during spray-drying. It was discovered that, the BCA-NC
      gel with 1% HLA possessed the favorable gelatin capacity and thinning shear
      rheological property. In vitro transdermal permeation studies of BCA-NC-gel/HLA
      studies indicated a marked increase in the skin permeation of BCA. And the
      transdermal flux of BCA-NC-gel with 1% HLA were 20.65-fold higher (p < 0.01) than
      that of coarse BCA-gel, which could be attributed to particles size reduction of
      BCA-NC and bioadhesive property of HLA. And the morphology characterization of
      BCA-NC-gel/HLA demonstrated that BCA-NC could be imprisoned into the gel network
      of HLA, which might prevent it from aggregation in gel. In conclusion, HLA based
      nanogel system is a promising carrier for effectively transdermal delivery of
      poorly soluble drug.

PMID- 30287045
TI  - Macroporous alginate foams crosslinked with strontium for bone tissue
      engineering.
AB  - Nowadays, the need of novel strategies to repair and regenerate bone defects in
      the field of biomedical applications has increased. Novel approaches include the
      design of natural bioactive scaffolds mimicking bone tissue. These bioactive
      scaffolds have to possess biophysical properties suitable to address biological
      response towards newly bone tissue formation. In particular, scaffold porosity
      and pore size play a pivotal role in cell migration, adhesion and proliferation,
      thus increasing cell-material surface interaction and osteogenic signals
      transmission. Here we propose the development of macroporous alginate foams
      (MAFs) with porous and well interconnected structure, useful to enhance growth
      and osteogenic differentiation of human Mesenchymal Stem Cells (hMSCs). Moreover,
      in this study we report a new method for MAFs fabrication based on the
      combination of internal gelation technique with gas foaming. Strontium was
      employed in combination with calcium as cross-linking agent for the alginate
      chains and as enhancer of the osteogenic differentiation. The influence of
      strontium ions on the gelation kinetics, physical properties and degradation in
      physiological medium of MAFs was investigated. Our results suggest that the
      combination of internal gelation technique with gas foaming followed by freeze
      drying is an easy and straightforward procedure to prepare alginate foams with
      high porosity and interconnectivity, able to support cell infiltration. Finally,
      biological assays showed how scaffolds with high strontium content are able to
      support cell growth and differentiation in long times by promoting osteogenic
      marker expression.

PMID- 30287046
TI  - Coupling chitosan and TEMPO-oxidized nanofibrilliated cellulose by electrostatic
      attraction and chemical reaction.
AB  - This study reports coupling methods of chitosan (CTS) and TEMPO-oxidized
      nanofibrilliated cellulose (TONCs). Coupling chitosan, a cationic polysaccharide,
      to anionic TONCs is preformed through physical crosslinking via ionic bond
      formation at room temperature and carefully controlled pH and mass ratio. After
      heating, the carboxyl group of TONCs and the ammonium group of chitosan react
      into an amide covalent bond linkage CONH. Fourier Transform infrared
      spectroscopy, 13C solid-state nuclear magnetic resonance, are used to confirm the
      bonds. Films of the modified TONC are produced by casting and exchanging method
      and atomic force microscopy and thermogravimetric analysis was used to study the
      film properties. Further, the tensile strength of the CTS-TONCs films is improved
      for the covalent bond produced indicating a straight forward method to augment
      the properties of these all-polysaccharide films.

PMID- 30287047
TI  - Multifunctional laminarin microparticles for cell adhesion and expansion.
AB  - Microfabrication technologies have been widely explored to produce microgels that
      can be assembled in functional constructs for tissue engineering and regenerative
      medicine applications. Here, we propose microfluidics coupled to a source of UV
      light to produce multifunctional methacrylated laminarin microparticles with
      narrow distribution of sizes using photopolymerization. The multifunctional
      microparticles were loaded with platelet lysates and further conjugated with an
      adhesive peptide. The adhesive peptides dictated cell adhesiveness to the
      laminarin microparticles, the incorporation of platelet lysates have resulted in
      improved cell expansion compared to clear microparticles. Overall, our findings
      demonstrate that multifunctional methacrylated laminarin microparticles provide
      an effective support for cell attachment and expansion. Moreover, expanded cells
      provide the link for microparticles aggregation resulting in robust 3D
      structures. This suggest the potential for using the methacrylated laminarin
      microplatforms capable to be assembled by the action of cells to rapidly produce
      large tissue engineered constructs.

PMID- 30287048
TI  - Strategy to improve the characterization of chitosan by size exclusion
      chromatography coupled with multi angle laser light scattering.
AB  - Here we present SEC-MALLS study for chitosan samples with weight average molar
      mass Mw between 33 and 427 kg/mol on columns packed with 8 MUm porous particles.
      A low injection concentration on the order of 0.1-0.2 mg/mL must be used to avoid
      overloading of the SEC columns, due to the extended coil conformation of cationic
      chitosan in the dilute acid buffer as compared to neutral polymers. Additionally,
      SEC must be performed at an eluent flow rate no more than 0.5 mL/min for high
      molar mass chitosan samples. At flow rates of 1.0 and 1.5 mL/min, the elution of
      the largest chitosan species is delayed, which leads to a distortion of the molar
      mass distribution towards lower molar mass region. Such an abnormal behavior is
      due to a chromatographic mode transition from SEC to slalom chromatography,
      originated from the coil-stretch transition of chitosan chains in elongational
      flow through the packed columns.

PMID- 30287049
TI  - Reply to: "Replicability of exercise programs following bariatric surgery".

PMID- 30287050
TI  - Serum FABP4 concentrations decrease after Roux-en-Y gastric bypass but not after
      intensive medical management.
AB  - BACKGROUND: Serum concentrations of fatty acid binding protein 4, an adipose
      tissue fatty acid chaperone, have been correlated with insulin resistance and
      cardiovascular risk factors. The objective of this study were to assess
      relationships among Roux-en-Y gastric bypass, intensive lifestyle modification
      and medical management protocol, fatty acid binding protein 4, and metabolic
      parameters in obese patients with severe type 2 diabetes mellitus; and to
      evaluate the relative contribution of abdominal subcutaneous adipose and visceral
      adipose to the secretion of fatty acid binding protein 4. METHODS: Participants
      were randomly assigned to intensive lifestyle modification and medical management
      protocol (n = 29) or to intensive lifestyle modification and medical management
      protocol augmented with Roux-en-Y gastric bypass (n = 34). Relationships among
      fatty acid binding protein 4 and demographic characteristics, metabolic
      parameters, and 12-month changes in these values were examined. Visceral and
      subcutaneous adipose tissue explants from obese nondiabetic patients (n = 5) were
      obtained and treated with forskolin to evaluate relative secretion of fatty acid
      binding protein 4 in the different adipose tissue depots. RESULTS: The intensive
      lifestyle modification and medical management protocol and Roux-en-Y gastric
      bypass cohorts had similar fasting serum fatty acid binding protein 4
      concentrations at baseline. At 1 year, mean serum fatty acid binding protein 4
      decreased by 42% in Roux-en-Y gastric bypass participants (P = .002) but did not
      change significantly in the intensive lifestyle modification and medical
      management protocol cohort. Percentage of weight change was not a significant
      predictor of 12-month fatty acid binding protein 4 within treatment arm or in
      multivariate models adjusted for treatment arm. In adipose tissue explants, fatty
      acid binding protein 4 was secreted similarly between visceral and subcutaneous
      adipose tissue. CONCLUSION: After Roux-en-Y gastric bypass, fatty acid binding
      protein 4 is reduced 12 months after surgery but not after intensive lifestyle
      modification and medical management protocol in patients with type 2 diabetes
      mellitus. Fatty acid binding protein 4 was secreted similarly between
      subcutaneous and visceral adipose tissue explants.

PMID- 30287052
TI  - The burden of Parkinson's disease: a worldwide perspective.

PMID- 30287053
TI  - Celastrol Reverses Palmitic Acid-Induced Insulin Resistance in HepG2 Cells via
      Restoring the miR-223 and GLUT4 Pathway.
AB  - OBJECTIVES: The natural triterpenoid compound celastrol ameliorates insulin
      resistance (IR) in animal models, but the underlying molecular mechanism is
      unclear. In this study, we investigated how celastrol regulates IR. METHODS: The
      HepG2 cellular IR model was initially established with palmitic acid (PA). The
      expression and activity of glucose transporter 4 (GLUT4), insulin receptor
      substrate-1 (IRS1) and 9 microRNAs (miRNAs) (miR-7, -34a, -96, -113, -126, -145, 
      150, -223 and -370) were detected before and after celastrol treatment using the
      PA-induced HepG2 IR model. RESULTS: The results showed that 250 uM PA for >=2
      days was optimal for inducing IR in HepG2 cells; 600 nM celastrol significantly
      attenuated the PA-induced IR in HepG2 cells. The PA-induced GLUT4 and IRS1
      downregulation and Ser307 phosphorylation on IRS1 was reversed by subsequent
      treatment with 600 nM celastrol for 6 h. We next investigated which IR-related
      miRNAs were possible upstream regulators of celastrol-mediated reversal of PA
      induced HepG2 IR. Two miRNAs, miR-150 and -223, were significantly downregulated
      by PA and were re-raised by subsequent celastrol treatment; and miR-223 was
      upstream of miR-150. Moreover, knocking down miR-223 abolished celastrol's anti
      IR effects in the PA-induced model. CONCLUSIONS: Collectively, our results
      demonstrated that celastrol reverses PA-induced IR-related alterations, in part
      via miR-223 in HepG2 cells. Further investigation is warranted for establishing
      the clinical potential of celastrol in treating IR-related disorders.

PMID- 30287051
TI  - Global, regional, and national burden of Parkinson's disease, 1990-2016: a
      systematic analysis for the Global Burden of Disease Study 2016.
AB  - BACKGROUND: Neurological disorders are now the leading source of disability
      globally, and ageing is increasing the burden of neurodegenerative disorders,
      including Parkinson's disease. We aimed to determine the global burden of
      Parkinson's disease between 1990 and 2016 to identify trends and to enable
      appropriate public health, medical, and scientific responses. METHODS: Through a
      systematic analysis of epidemiological studies, we estimated global, regional,
      and country-specific prevalence and years of life lived with disability for
      Parkinson's disease from 1990 to 2016. We estimated the proportion of mild,
      moderate, and severe Parkinson's disease on the basis of studies that used the
      Hoehn and Yahr scale and assigned disability weights to each level. We jointly
      modelled prevalence and excess mortality risk in a natural history model to
      derive estimates of deaths due to Parkinson's disease. Death counts were
      multiplied by values from the Global Burden of Disease study's standard life
      expectancy to compute years of life lost. Disability-adjusted life-years (DALYs)
      were computed as the sum of years lived with disability and years of life lost.
      We also analysed results based on the Socio-demographic Index, a compound measure
      of income per capita, education, and fertility. FINDINGS: In 2016, 6.1 million
      (95% uncertainty interval [UI] 5.0-7.3) individuals had Parkinson's disease
      globally, compared with 2.5 million (2.0-3.0) in 1990. This increase was not
      solely due to increasing numbers of older people, because age-standardised
      prevalence rates increased by 21.7% (95% UI 18.1-25.3) over the same period
      (compared with an increase of 74.3%, 95% UI 69.2-79.6, for crude prevalence
      rates). Parkinson's disease caused 3.2 million (95% UI 2.6-4.0) DALYs and 211 296
      deaths (95% UI 167 771-265 160) in 2016. The male-to-female ratios of age
      standardised prevalence rates were similar in 2016 (1.40, 95% UI 1.36-1.43) and
      1990 (1.37, 1.34-1.40). From 1990 to 2016, age-standardised prevalence, DALY
      rates, and death rates increased for all global burden of disease regions except
      for southern Latin America, eastern Europe, and Oceania. In addition, age
      standardised DALY rates generally increased across the Socio-demographic Index.
      INTERPRETATION: Over the past generation, the global burden of Parkinson's
      disease has more than doubled as a result of increasing numbers of older people,
      with potential contributions from longer disease duration and environmental
      factors. Demographic and potentially other factors are poised to increase the
      future burden of Parkinson's disease substantially. FUNDING: Bill & Melinda Gates
      Foundation.

PMID- 30287054
TI  - The Health and Health Care of Adults With Type 1 And 2 Diabetes Across the
      Spectrum of Estimated Glomerular Filtration Rates.
AB  - OBJECTIVES: Little is known about the health and health-care patterns of patients
      with diabetes according to their estimated glomerular filtration rates,
      especially within a publicly funded health-care system. METHODS: Using linked
      health-care databases in Ontario, Canada, we performed a population-based study
      of adults 50 years of age and older (mean age, 68 years) with prevalent diabetes
      on January 1, 2014. We categorized patients according to their levels of kidney
      function (estimated glomerular filtration rate >=90, 60 to 89, 30 to 59, 15 to 29
      or <15 mL/min/1.73 m2, or the receipt of ongoing maintenance dialysis). We then
      followed patients for 2 years to determine: 1) their level of contact with health
      care providers (i.e. visits to family doctors, specialists); 2) their use and
      repeated use of acute medical services (i.e. hospitalizations and emergency
      department encounters; 3) diabetes-related monitoring and screening (i.e.
      glycated hemoglobin and cholesterol tests, vision screening); 4) glycemic and
      lipid control; and 5) diabetes-related outcomes. RESULTS: There were 569,384
      patients in our study. Most had estimated glomerular filtration rates between 60
      and 89 mL/min/1.73 m2. At baseline, patients with lower kidney function had
      longer durations of diabetes and more comorbidities. Over 2 years of follow up,
      they had higher burdens of medical care, excessive diabetes monitoring and were
      underscreened for diabetes-related complications. Although metabolic control was
      reasonable across groups, patients with low kidney function had more hospital
      encounters and more diabetes-related complications. CONCLUSIONS: Patients with
      diabetes and low kidney function are a vulnerable population that faces health
      system challenges and care gaps. Suggestions for policy and practice are
      discussed.

PMID- 30287055
TI  - Independent of left ventricular mass, circulating inflammatory markers rather
      than pressure load are associated with concentric left ventricular remodelling.
AB  - BACKGROUND: A reason for concentric left ventricular (LV) remodelling predicting
      cardiovascular outcomes independent of conventional risk factors and LV mass
      (LVM) has not been provided. We hypothesized that independent of LVM, concentric
      LV remodelling is associated with inflammatory changes rather than a pressure
      load on the LV. METHODS: In 764 randomly selected community participants, we
      assessed relations between several inflammatory markers (ELISA) and LV relative
      wall thickness (RWT) (echocardiography), LV mass index (LVMI), and indexes of
      diastolic function. RESULTS: No independent relations were noted between
      circulating concentrations of inflammatory markers and LVM index (LVMI) (p > 0.13
      for all). However, independent of confounders including LVMI and blood pressure
      (BP), circulating tumour necrosis factor-alpha (TNF-alpha) (partial r = 0.14, p <
      0.0005) and to a lesser degree interleukin-6 (partial r = -0.09, p < 0.02) were
      associated with RWT. The impact (standardized beta-coefficient) of TNF-alpha on
      RWT (0.12 +/- 0.03, p < 0.0005) was at least as strong as age (0.13 +/- 0.05, p <
      0.005), and second only to LVMI (0.27 +/- 0.04, p < 0.0001), whilst neither
      office, 24-hour, central aortic BP, nor aortic stiffness were associated with RWT
      independent of LVMI. With adjustments, as compared to participants with a normal
      LVMI and geometry (12.7 +/- 0.8), circulating TNF-alpha concentrations (pg/ml)
      were increased as much in participants with concentric LV remodelling (16.8 +/-
      1.5, p < 0.05) as in those with concentric LV hypertrophy (LVH) (17.0 +/- 1.3, p
      < 0.005), whilst eccentric LVH (13.7 +/- 0.9) was not. No independent relations
      between inflammatory markers and LV diastolic function (trans-mitral and tissue
      Doppler) were noted. CONCLUSIONS: Independent of LVMI, a pro-inflammatory state
      rather than BP load is strongly associated with LV concentric remodelling.

PMID- 30287056
TI  - Efficacy and safety of cryoballoon ablation in the elderly: A multicenter study.
AB  - BACKGROUND: The prevalence of atrial fibrillation (AF) increases with age. Second
      generation cryoballoon (CB2)-based PVI has demonstrated encouraging clinical
      results in the treatment of paroxysmal (PAF) and persistent atrial fibrillation
      (PersAF). The objective of this study was to assess data on safety, efficacy and
      long-term clinical success of CB2-based pulmonary vein isolation (PVI) in
      patients >=75 years of age. METHODS: CB2-based PVI was performed in 104 patients
      >=75 years of age (elderly group) and symptomatic AF (PersAF: n = 44, 42.3%) in
      three highly experienced German EP centers. The data was compared to propensity
      score matched patients with age <75 years (n = 104, control group; PersAF: n =
      45, 43.3%, p = 0.956). RESULTS: The median age of the elderly group was 77.5 [75,
      80] years while it was 63 [52, 70] years of control group patients (p = 0.0001).
      The median procedure time was 92.5 [75, 120] minutes (elderly group) and 100 [75,
      120] (control group), p = 0.124. Major complications were registered in 7/104
      (6.7%) elderly patients and 7/104 (6.7%) control group patients (p = 0.999).
      Clinical success in terms of freedom from AF recurrence after one-year follow-up
      was 80% (95% CI: 72-88) and 82% (95% CI: 75-90) and after three-year follow-up
      59% (95% CI: 47-74) and 49% (95% CI: 37 64) for the elderly group and the control
      group, respectively (p = 0.7). CONCLUSIONS: CB2-based PVI in patients >=75 years
      of age appears safe, is associated with low procedure times and shows promising
      clinical success rates equal to patients of the younger population.

PMID- 30287057
TI  - Cardiac interventions and cardiac surgery and pregnancy.
AB  - Both cardiac surgery and cardiac interventions are rare in pregnancy but are
      generally more common in the developing world. Women with known cardiac disease
      should receive contemporaneous preconception counselling to assess all risks
      associated with pregnancy including whether surgery or cardiac interventions may
      need to be considered prior to pregnancy. Some women may need to undergo
      emergency surgery or procedures during pregnancy and decisions regarding this
      should be multidisciplinary including cardiologists, cardiac surgeons,
      anaesthetists, obstetricians and neonatologists. In this review we discuss both
      conditions where surgery or percutaneous interventions may need to be considered
      and both the outcomes for the mother and her baby.

PMID- 30287059
TI  - Update on the long-term cost-effectiveness of on-pump and off-pump coronary
      artery bypass grafting.

PMID- 30287060
TI  - Optimization of production rate, productivity, and product concentration for a
      simulated moving bed process aimed atfucose separation using standing-wave-design
      and genetic algorithm.
AB  - The effectiveness of a simulated moving bed (SMB) technology in the continuous
      separation of fucose from a multi-component monosugar mixture, which stemmed from
      defatted microalgae, has recently been identified. To guarantee high economical
      efficiency of such fucose-production method, the comprehensive optimization of
      the relevant fucose-separation SMB process needs to be accomplished such that its
      production rate (Prate) and/or productivity (Prod) can be maximized while meeting
      the requirements on fucose product concentration (Cprod,F) and pressure drop
      (DeltaPSMB). To resolve this issue, the SMB optimization program based on
      standing-wave-design method and genetic algorithm was prepared and then applied
      to the fucose-separation SMB optimization. It was found that the Prate, under a
      given particle size, could reach its maximum when the column length was selected
      to create a balance between the effects of the two limiting factors related to
      Cprod,F and DeltaPSMB. It was also found that the Prate was governed by fucose
      yield, if the SMB would be in need of a relatively high Cprod,F; otherwise, the
      Prate was governed by feed flow rate. If the particle size of the SMB adsorbent
      was fixed at one of the commercially available ones, the SMB conditions leading
      to the highest Prate and the highest Prod coincided with each other. By contrast,
      if the particle size was included as one of optimization variables, the Prate and
      Prod represented a trade-off relationship. Finally, it was confirmed from the
      simultaneous optimization for Prate and Prod that the increase of particle size
      improved Prate at the cost of Prod, thereby causing the maximum Prod to be always
      attained at a smaller particle size than the maximum Prate regardless of the
      target Cprod,F level.

PMID- 30287058
TI  - One-year clinical outcomes in older patients with non-ST elevation acute coronary
      syndrome undergoing coronary angiography: An analysis of the ICON1 study.
AB  - AIMS: The aim of this prospective, observational study was to identify predictors
      of adverse outcome at one year, following invasive care of older patients with
      non-ST-elevation acute coronary syndrome (NSTEACS) according to frailty status.
      METHODS: Older patients (aged >= 75 years), presenting with NSTEACS, undergoing
      invasive coronary angiography with a view to revascularisation, underwent
      assessment of frailty, cognition, functional status and quality of life.
      Participants were categorised as robust, pre-frail or frail using the Fried
      criteria. The primary outcome comprised a composite of all-cause mortality,
      myocardial infarction, stroke, unplanned revascularisation and major bleeding, at
      one year. Cox proportional hazards regression was used to derive a multivariate
      risk score. RESULTS: Overall, the composite endpoint was observed in 81
      participants (29%). There was a significant difference in the occurrence of the
      primary outcome in the 3 frailty groups (robust 18.0%, pre-frail 27.5% and frail
      39%; p = 0.03; hazard ratio (HR) for frail vs. robust: 2.79, 95% Confidence
      Interval [CI] 1.28-6.08). Fried frailty classification, age (categorised as >=85
      years), raised Killip class, systolic blood pressure on admission, history of
      peripheral vascular disease (PVD), problems dressing self and implantation of a
      bare metal stent were identified as predictors of adverse events at one year,
      with a C-statistic of 0.77 (95% CI 0.71-0.83). A point-based clinical risk score
      (FRAIL-HEART) was defined, which had a C-statistic of 0.70 (95% CI 0.63-0.77) and
      significantly outperformed the GRACE 2 score. CONCLUSION: Frailty is associated
      with adverse clinical outcomes, following invasive management of older patients
      with NSTEACS. The derived risk models may enable improved risk stratification in
      practice.

PMID- 30287061
TI  - Thin-layer chromatogram development with a moving pipette delivering the mobile
      phase onto the surface of the adsorbent layer.
AB  - The new approach to the development of thin-layer chromatograms is presented. For
      the first time we show flexible mobile phase dosage onto the surface of the
      adsorbent layer by moving pipette combined with precise syringe pumps. The
      pipette is driven into movement by computer controlled 3D machine (modified 3D
      printer mechanism). Delivery of the mobile phase to the adsorbent layer is equal
      to or lower than that of conventional development. Therefore chromatograms can be
      developed with optimal mobile phase velocity, adjusted to its absorption rate by
      the adsorbent layer. Under such conditions there is no excess of eluent on the
      surface of the adsorbent layer so higher performance of the chromatographic
      system can be obtained. Moreover chromatograms can be developed with constant
      linear mobile phase velocity and therefore the relationships the plate height vs.
      mobile phase linear velocity obtained with planar chromatography driven by
      capillary forces are investigated and reported. In addition the contribution of
      starting spot variance in total peak variance and the influence of narrowing of
      starting spots on performance of the chromatographic system have been studied.
      The results confirm a very significant starting spot variance contribution to
      total peak variance and consequently considerable influence of starting spot size
      on plate height of the separation system, when chromatogram is developed on a
      short distance. In the paper the advantages and disadvantages of the prototype
      device and its possible application are discussed.

PMID- 30287062
TI  - Significant sensitivity enhancement in Hadamard transform high-performance liquid
      chromatography by application of long modulation sequences constructed from lower
      order sequences.
AB  - Hadamard encoding, utilizing pseudo-random injection sequences with n-bit (2n-1)
      elements, is applied in analytical sciences to enhance the signal-to-noise ratio
      (S/N) of weak analyte signals. We have developed a software approach that allows
      using Hadamard encoding on standard HPLC systems. This strategy is only limited
      by the number of instructions that can be transmitted to the autosampler and its
      performance degrades if an accumulation of chromatographic irregularities occurs
      while applying long modulation sequences. Here we demonstrate that such sequences
      (>4000 elements) can be subdivided into suitable subsequences, which can be
      independently executed. The measured subchromatograms are subsequently realigned
      and deconvoluted yielding a chromatogram with increased S/N. This opens an avenue
      to achieve unprecedented sensitivity gains. In the analysis of highly diluted
      nucleoside samples an S/N enhancement of up to 30-fold was observed. Furthermore,
      we applied the method to a sample containing the antibiotic drug fidaxomicin and
      found a significant sensitivity improvement that strongly depends on the applied
      elution conditions.

PMID- 30287063
TI  - The compound-independent calibration of polybrominated diphenyl ethers isomers
      using gas chromatography-inductively coupled plasma mass spectrometry.
AB  - Compound-independent calibration (CIC) is a quantitative method that can quantify
      other compounds using a structure-independent compound as the calibrant. In this
      study, the potential and application of CIC method for the determination of
      polybrominated diphenyl ethers (PBDEs) using GC-ICP-MS was investigated. The
      effects of sample introduction conditions, the flow rate of the carrier gas,
      splitless delay time and the matrix of the complex sample on the response of 11
      PBDEs compounds were explored. When pulsed splitless injection was used, the
      transmission efficiency of analytes from the inlet to the column can speed up
      with increasing injection temperature and pulse pressure, the elemental response
      of bromine of each analyte becomes closer. Under optimized chromatographic
      conditions, the response is independent of the compound can be found from the
      slope of the pure solution standard from tri- to hepta- brominated compounds (BDE
      28 as reference) ranged from 0.968 to 1.001 (R2>0.998). The degradation ratio of
      BDE 209 in the GC-ICP/MS system was estimated by the CIC method to be 18.7%.
      During the determination of fish tissue sample, big difference of the elemental
      response ratio (BDE 28 as reference) was obtained range from 0.678 to 0.976.
      However, a similar elemental response was observed among isomers range from 0.990
      to 1.056. This may mean that the isomers can be calibrated to each other in a
      complex matrix sample. The CIC method was validated by determination 3 PBDEs in
      NIST SRM 1947 frozen fish tissue certified reference materials using isomers as
      reference compounds. The recoveries of BDE 49 and BDE 66 were 105.7% and 88.1% by
      using BDE 47 as calibrants, and that of BDE 155 was 108.8% by using BDE 154 as
      calibrant.

PMID- 30287064
TI  - Determination of steviol glycosides in commercial extracts of Stevia rebaudiana
      and sweeteners by ultra-high performance liquid chromatography Orbitrap mass
      spectrometry.
AB  - Stevia rebaudiana extracts are used as sweeteners in several countries worldwide.
      Several extracts of diverse composition are available on the market, and their
      taste depends on the contents of the various steviol glycosides. This study
      presents an accurate method for the qualitative and quantitative determination of
      steviol glycosides in 40 Stevia extracts, 7 sweeteners and 3 Stevia-sweetened
      beverages by a UHPLC coupled to an Orbitrap mass spectrometer. The sub-2 MUm
      amide column provided the separation of all the target analytes in a run time of
      30 min with high resolution. The effect of different eluent compositions on the
      ionisation efficiency of the steviol glycosides was studied. The optimal
      ionisation conditions were achieved in negative mode using 0.05% formic acid.
      Under this condition, adducts were not found, [M-H]- were the main ions and the
      spontaneous loss of a glucose residue at C19 was reduced. The %RSD for intra- and
      inter-day precision for all eleven analytes varied from 2.1 to 4.2% and 3.0-5.1%,
      respectively. The recoveries from spiked Stevia extract samples were greater than
      95% for all analytes. Rebaudioside A was the most abundant, ranging from 23 to
      102%. Nine Stevia extracts and one drink were not compliant with the European
      Regulation. Isosteviol was under the LOD in all samples and steviol was found in
      four samples in quantities in the range 0.01-0.03%.

PMID- 30287065
TI  - Patient Safety in Audiology.
AB  - There is a need to educate audiologists, physicians, and other clinicians about
      patient safety in audiology. This article addresses the many aspects of patient
      safety and the applicability to the practice of audiology in health care.
      Clinical examples of strategies to build a culture of patient safety are
      provided.

PMID- 30287066
TI  - Intermittent Hypoxemia in Infants Born Late Preterm: A Prospective Cohort
      Observational Study.
AB  - OBJECTIVE: To determine if late preterm infants are at increased risk of
      intermittent hypoxemic events compared with term infants. STUDY DESIGN:
      Prospective, cohort, observational study of late preterm infants (340/7-366/7
      weeks gestational age) and term infants (390/7-416/7 weeks gestational age).
      Overnight pulse oximetry recordings were performed on days 2-3 after birth, at
      term equivalent age, and at 45 weeks postmenstrual age. The primary outcome was
      the frequency of intermittent hypoxemic events per hour (desaturation >=10% below
      the preceding baseline SpO2) on the oximetry recording on days 2-3 after birth.
      Data were analyzed by the Student t test and general linear mixed model. RESULTS:
      Eighty-five infants were enrolled (late preterm n = 43; term infants n = 42). On
      days 2-3 after birth, late preterm infants had more intermittent hypoxemic events
      than term infants (events per hour, mean +/- standard error of the mean, 2.5 +/-
      1.2 vs 1.0 +/- 1.2; P < .0001). On mixed model analysis, late preterm infants had
      a higher frequency of intermittent hypoxemic events at term equivalent age, which
      decreased to a similar frequency as in term infants by 45 weeks postmenstrual age
      (events per hour; term equivalent age, late preterm: least squares mean, 3.7 [95%
      CI, 2.7-5.1] vs term: least squares mean, 1.7 [95% CI, 1.2-2.3]; 45 weeks
      postmenstrual age, late preterm: least squares mean, 1.5 [95% CI, 1.1-2.1] vs
      term: least squares mean, 1.9 [95% CI, 1.4-2.6]; P < .0005). CONCLUSIONS: Late
      preterm infants are at greater risk of intermittent hypoxemia than term infants
      soon after birth. We speculate that preventing intermittent hypoxemia in late
      preterm infants may improve neurodevelopmental outcomes.

PMID- 30287067
TI  - Adverse Childhood Experiences and Weight Status among Adolescents.
AB  - OBJECTIVE: To investigate the relationship between adverse childhood experiences
      (ACEs) and weight status among adolescents. STUDY DESIGN: Data were drawn from
      the Minnesota Student Survey, a large (n = 105 759), statewide, anonymous survey
      of public school students in eighth, ninth, and eleventh grades. Self-reported
      height and weight were used to calculate body mass index. Multinomial logistic
      regression was used to examine associations between self-reported ACEs and weight
      status, controlling for key sociodemographic characteristics. RESULTS: ACEs were
      positively associated with weight status; adolescents with more ACEs were more
      likely to have overweight, obesity, and severe obesity than adolescents with no
      ACEs. Adolescents who reported an ACE were 1.2, 1.4, and 1.5 times as likely to
      have overweight, obesity, and severe obesity, respectively, compared with their
      peers with no ACEs. There was no relationship between ACEs and underweight.
      CONCLUSIONS: The results of this large sample of adolescents with anonymous data
      support the hypothesis that ACEs and obesity are strongly associated. The
      directionality of this relationship needs to be understood. Moreover, these
      findings suggest that child health professionals may need to screen for ACEs as
      an important aspect of clinical weight management.

PMID- 30287068
TI  - Role of Genetic Susceptibility in the Development of Bronchopulmonary Dysplasia.
AB  - OBJECTIVE: To assess heritable contributions to bronchopulmonary dysplasia (BPD)
      risk in a twin cohort restricted to gestational age at birth <29 weeks. STUDY
      DESIGN: A total of 250 twin pairs (192 dichorionic, 58 monochorionic) born <29
      weeks gestational age with known BPD status were identified. Three statistical
      methods applicable to twin cohorts (chi2 test, intraclass correlations [ICCs],
      and ACE modeling [additive genetic or A, common environmental or C, and unique
      environmental or E components]) were applied. Heritability was estimated as
      percent variability from A. Identical methods were applied to a subcohort defined
      by zygosity and to an independent validation cohort. RESULTS: chi2 analyses
      comparing whether neither, 1, or both of monochorionic (23, 19, 16) and
      dichorionic (88, 56, 48) twin pairs developed BPD revealed no difference.
      Although there was similarity in BPD outcome within both monochorionic and
      dichorionic twin pairs by ICC (monochorionic ICC = 0.34, 95% CI [0.08, 0.55];
      dichorionic ICC = 0.39, 95% CI [0.25, 0.51]), monochorionic twins were not more
      likely than dichorionic twins to have the same outcome (P = .70). ACE modeling
      revealed no contribution of heritability to BPD risk (% A = 0.0%, 95% CI [0.0%,
      43.1%]). Validation and zygosity based cohort results were similar. CONCLUSIONS:
      Our analysis suggests that heritability is not a major contributor to BPD risk in
      preterm infants <29 weeks gestational age.

PMID- 30287069
TI  - Preschoolers understand and generate pretend actions using object substitution.
AB  - Pretend play is often considered to be an imaginative or creative activity. Yet
      past experimental research has focused on whether children imitate pretense,
      follow instructions to pretend, or understand others' pretense. Thus, we cannot
      be sure that children's pretense is in fact novel or whether children simply copy
      or follow others' instructions. This is the first experiment to show that
      preschoolers generate their own novel object substitutions. In Study 1, 45 3- and
      4-year-olds saw an experimenter use one object as another accompanied by pretend
      or trying cues. Children differentiated between the experimenter's intentions by
      imitating the actions accompanied by pretend cues and correcting the actions
      accompanied by trying cues. In addition, when the experimenter made her
      intentions to pretend or try explicit, children produced significantly more novel
      object substitutions not modeled or verbally requested by the experimenter within
      a pretend context than within a trying context. Study 2 replicated these findings
      with 34 3-year-olds using a repeated-measures design. However, it found no
      relationship between children's copying or generation of object substitutions and
      divergent thinking, inhibitory control, or pretense during free play.

PMID- 30287070
TI  - Lipoprotein apheresis in the management of severe hypercholesterolemia and
      hyperlipoproteinemia(a)-The Portuguese experience.
AB  - BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a)
      (Lp(a)) are established causal risk factors for cardiovascular disease (CVD).
      Lipoprotein apheresis is often required for treatment of patients with a high
      risk for CVD due to hypercholesterolemia and/or hyperlipoproteinemia(a). AIM: To
      describe our experience with lipoprotein apheresis in patients with severe
      hypercholesterolemia or with hyperlipoproteinemia(a). METHODS: We retrospectively
      investigated patients treated with Lipoprotein apheresis using direct adsorption
      of lipoproteins (DALI) technique, between December 2008 and March 2018, in our
      center. Adverse events, acute and long term reductions in lipid parameters were
      analyzed. RESULTS: Between December 2008 and March 2018, a total of 950
      treatments were performed in five patients, four with heterozygous familial
      hypercholesterolemia (HeFH), all on maximally tolerated cholesterol-lowering drug
      therapy and in one patient with hyperlipoproteinemia(a) and progressive CVD. In
      the four patients with HeFH we obtained mean acute reductions in LDL-C and non
      high-density lipoprotein cholesterol (non-HDL-C) of 62.0 +/- 7.8% and 60.4 +/-
      6.8%, respectively. Regarding long-term efficacy we achieved a mean reduction of
      43.1% in LDL-C and of 41.2% in non-HDL-C. In the patient with
      hyperlipoproteinemia(a) we attained mean acute reductions of 60.4 +/- 6.4% in
      Lp(a) and of 75.4 +/- 7.3% in LDL-C per session and long term reductions in Lp(a)
      and LDL-C of 67.4% and 40.5%, respectively. Adverse events were recorded in only
      1.2% of treatments. CONCLUSION: Lipoprotein apheresis is an efficient and safe
      treatment in severely hypercholesterolemic patients who are refractory to
      conservative lipid-lowering therapy or with hyperlipoproteinemia(a) and
      progressive CVD.

PMID- 30287071
TI  - Risks of leukapheresis and how to manage them-A non-systematic review.
AB  - Leukapheresis is like any other preparative apheresis, except it isn't:
      Leukapheresis typically takes much longer, larger blood volumes are processed
      and, consequently, larger ACD-A volumes are administered. Blood component donors
      and leukapheresis subjects are also quite different populations. Allogeneic
      donors tend to be younger and many are first-time donors, both of which are risk
      factors for adverse reactions during blood donation. Moreover, more than half of
      all leukapheresis collections are performed in patients. Here it is the age
      distribution, including patients at the extremes of age, as well as the
      underlying disease and co-morbidities which may expose them to higher, or
      different, risks compared to donors. Both groups thus have good reasons why
      adverse effects to leukapheresis might be more frequent, more severe, or even
      different in nature altogether. Compared to other preparative apheresis types
      like platelet or plasma apheresis, the risks of leukapheresis have been studied
      less extensively, as it is in comparison a relatively low-frequency intervention.
      Often leukapheresis remains a domain of hematologists who have a different sense
      of procedural safety than transfusionists. Furthermore, G-CSF mobilized "stem
      cell" aphereses by a wide margin outnumber unmobilized aphereses, so that the
      very strong signal from adverse reactions to G-CSF all but drowns out signals
      from the apheresis proper. This focused review assesses observations from
      leukapheresis as well as extrapolation of observations from other forms of
      preparative apheresis in an attempt to gauge the safety of leukapheresis and
      identify potential approaches to its further improvement. In short, the overall
      impression is one of a very satisfactory safety record of leukapheresis, with
      occasional issues with venous access or vasovagal problems, and frequent, but
      highly responsive and rarely limiting ACD-A toxicity.

PMID- 30287072
TI  - Instantaneous frequency as a new approach for evaluating the clinical severity of
      Duchenne muscular dystrophy through ultrasound imaging.
AB  - Duchenne muscular dystrophy (DMD) results in loss of ambulation for the patients.
      Ultrasound attenuation correlates with fat content in muscles, resulting in
      changes in signal frequency. The Hilbert-Huang transform (HHT) allows time
      frequency analysis with high time-frequency resolution. This study explored the
      feasibility of using the instantaneous frequency (IF) obtained from the HHT to
      diagnose the walking function of patients with DMD. Eighty-five participants (12
      control and 73 patients with DMD) underwent a standard-care ultrasound
      examination of the gastrocnemius to acquire raw image data for ultrasound B-mode
      and IF calculations, which were compared with the DMD stage using Pearson
      correlation and receiver operating characteristic (ROC) curve analyses. With
      increasing DMD stage, the median IF decreased from 7.25 to 7.01 MHz (the
      correlation coefficient r = -0.73; the probability value p < 0.0001). The area
      under the ROC curve was 0.97 when using ultrasound IF to discriminate between
      ambulatory and nonambulatory patients (accuracy: 91.76%; sensitivity: 93.75%; and
      specificity: 90.57%). The study reveals that ultrasound IF has great potential in
      DMD evaluation and management.

PMID- 30287073
TI  - Numerical prediction of ultrasonic attenuation in concentrated emulsions and
      suspensions using Monte Carlo method.
AB  - For the study of predicting ultrasonic attenuation of mixed particles and probing
      the effect of interaction between neighboring particles, the Monte Carlo method
      was investigated to establish a submicron particle size characterization model in
      concentrated particulate two-phase system and serve as a probability and
      statistics technique to evaluate the underlying ultrasonic events during the
      ultrasound propagation. The numerical simulation method was proposed to predict
      the ultrasonic attenuation characteristics in the two-phase system of silica
      suspensions and corn oil-in-water emulsions with different particle sizes,
      ultrasonic frequencies and concentrations. Furthermore, an extension of the well
      established single-particle theory of Epstein-Carhart and Allegra-Hawley (ECAH)
      was carried out, by incorporated in the couple phase model from a hydrodynamic
      point of view and effective hypothesis both accounted for the ultrasonic wave
      overlapping effect for the close proximity of particles. The simulation result
      shows agreement with the results of the ECAH model, the Lloyd & Berry (LB) model
      and the Waterman model in the dilute limitation, corresponding to glass beads and
      silica particles respectively. Afterwards, such a method was then applied into
      mixed particle system, where the mixed iron particles and glass beads with
      various ratios were set as examples for the purpose of predicting ultrasonic
      attenuation for the mixed particle systems. After comparing with the experimental
      results, it is shown that as a function of frequency, the variation of the
      ultrasonic attenuation coefficient with different mixing ratio manifests a
      nonlinear tendency. Also noteworthy is that the physical properties of particles
      play a dramatic impact in influencing ultrasonic attenuation. At higher
      concentrations, it was validated both in two-phase system of silica suspensions
      and corn oil-in-water emulsions that the attenuation predicted by Monte Carlo
      method agreed well with the experimental results of literature, yielding a
      theoretically increasing but less than linear expected attenuation with particle
      concentration. Particularly, the critical concentration of deviation from the
      linear change was obtained and interpreted using the thermal and viscous
      overlapping theory. The proposed Monte Carlo method presents a novel approach in
      calculating the attenuation in high particle volume concentration of more than
      40% and provides a numerical modeling of particle size measurement in the complex
      particle-particle interaction condition.

PMID- 30287074
TI  - Therapeutic Potential of OMe-PS-miR-29b1 for Treating Liver Fibrosis.
AB  - Trans-differentiation of quiescent hepatic stellate cells (HSCs) into active
      myofibroblasts secretes excess amounts of extracellular matrix (ECM) proteins.
      miR-29b1 has the potential to treat liver fibrosis, because it targets several
      profibrotic genes. We previously demonstrated that miR-29b1 and the hedgehog (Hh)
      pathway inhibitor GDC-0449 could, together, inhibit the activation of HSCs and
      ECM production in common bile-duct-ligated (CBDL) mice. Herein, we determined the
      effect of chemical modifications of miR-29b1 on its stability, immunogenicity,
      and Argonaute-2 (Ago2) loading in vitro, after modifying its antisense strand
      with phosphorothioate (PS-miR-29b1), 2'-O-methyl-phosphorothioate (OMe-miR-29b1),
      locked nucleic acid (LNA-miR-29b1), and N,N'-diethyl-4-(4-nitronaphthalen-1
      ylazo)-phenylamine (ZEN-miR-29b1). Chemical modifications significantly improved
      stability of miR-29b1 in 50% FBS. Among all the modified miRNAs tested, OMe-PS
      miR-29b1 showed the highest stability with low immunogenicity, without the loss
      of efficacy in vitro. Therefore, OMe-PS-miR-29b1 was complexed with poly(ethylene
      glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonate-graft-dodecanol-graft
      tetraethylenepentamine (mPEG-b-PCC-g-DC-g-TEPA) cationic micelles, and anti
      fibrotic efficacy was evaluated in CBDL mice. There was a significant improvement
      in liver histology and decrease in the levels of injury markers. Further,
      mRNA/protein levels of collagen, alpha-SMA, and TIMP-1 were significantly lower
      for the OMe-PS-miR-29b1-loaded micelles compared to miR-29b1-loaded micelles. In
      conclusion, micellar delivery of OMe-PS-miR-29b1 is a promising strategy to treat
      liver fibrosis.

PMID- 30287075
TI  - A straightforward approach for coping with unreliability of person means when
      parsing within-person and between-person effects in longitudinal studies.
AB  - Longitudinal studies enable researchers to distinguish within-person (i.e., time
      varying) from between-person (i.e., time invariant) effects by using the person
      mean to model between-person effects and person-mean centering to model within
      person effects using multilevel models (MLM). However, with some exceptions, the
      person mean tends to be based on a relatively small number of observations
      available for each participant in longitudinal studies. Unreliability inherent in
      person means generated with few observations results in downwardly biased between
      person and cross-level interaction effect estimates. This manuscript considers a
      simple, easy-to-implement, post-hoc bias adjustment to correct for attenuation of
      between-person effects caused by unreliability of the person mean. This
      correction can be applied directly to estimates obtained from MLM. We illustrate
      this method using data from a panel study predicting adolescent alcohol
      involvement from perceived parental monitoring, where parental monitoring was
      disaggregated into within-person (i.e., person-mean-centered) and between-person
      (i.e., person-mean) components. We then describe results of a small simulation
      study that evaluated the performance of the post-hoc adjustment under data
      conditions that mirrored those of the empirical example. Results suggested that,
      under a condition in which parameter bias is known to be problematic (i.e.,
      moderate ICCX, small n, presence of a compositional effect), it is preferable to
      use the bias-adjusted MLM estimates over the unadjusted MLM estimates for between
      person and cross-level interaction effects.

PMID- 30287076
TI  - Corrigendum to "Cadmium mass balance in French soils under annual crops:
      Scenarios for the next century" [Sci. Total Environ. 639 (2018) 1440-1452].

PMID- 30287077
TI  - Corrigendum to "Prospects of developing a prophylactic vaccine against human
      lymphatic filariasis - evaluation of protection in non-human primates" [Int. J.
      Parasitol. 48 (2018) 773-783].

PMID- 30287078
TI  - Intradiploic epidermoid cyst of the temporal and occipital bone with intracranial
      extension.

PMID- 30287080
TI  - Sensory Exploitation, Sexual Dimorphism, and Human Voice Pitch.
AB  - Selection for low male voice pitch is generally assumed to occur because it is a
      valid cue of formidability. Here we summarize recent empirical challenges to this
      hypothesis. We also outline an alternative account in which selection for low
      male voice pitch is a byproduct of sensory exploitation.

PMID- 30287079
TI  - Donor APOL1 high-risk genotypes are associated with increased risk and inferior
      prognosis of de novo collapsing glomerulopathy in renal allografts.
AB  - Collapsing focal segmental glomerulosclerosis (cFSGS) in the native kidney is
      associated with heavy proteinuria and accelerated renal failure. However, cFSGS
      in the renal allograft is less well characterized. Here we report clinico
      pathologic features and APOL1 donor risk genotypes in 38 patients with de novo
      post-kidney transplant cFSGS. Recipients were 34% female and 26% African
      American. Concurrent viral infections and acute vaso-occlusion (including
      thrombotic microangiopathy, cortical necrosis, atheroembolization, and cardiac
      arrest with contralateral graft thrombosis) were present in 13% and 29% of
      recipients, respectively. Notably, 61% of patients had concurrent acute rejection
      and 47% received grafts from African American donors, of which 53% carried APOL1
      high-risk genotypes. These frequencies of acute rejection and grafts from African
      American donors were significantly higher than in our general transplant
      population (35% and 16%, respectively). Patients had a median serum creatinine of
      5.4 mg/dl, urine protein/creatinine 3.5 g/g, and 18% had nephrotic syndrome.
      Graft failure occurred in 63% of patients at an average of eighteen months post
      index biopsy. By univariate analysis, donor APOL1 high-risk genotypes, post
      transplant time, nephrotic syndrome, and chronic histologic changes were
      associated with inferior graft survival while acute vaso-occlusion was associated
      with superior graft survival. Donor APOL1 high-risk genotypes independently
      predicted poor outcome. Compared to native kidney cFSGS, post-transplant cFSGS
      had more acute vaso-occlusion but less proteinuria. Thus, de novo cFSGS is
      associated with variable proteinuria and poor prognosis with potential
      predisposing factors of African American donor, acute rejection, viral infection
      and acute vaso-occlusion. Additionally, donor APOL1 high-risk genotypes are
      associated with higher incidence and worse graft survival.

PMID- 30287081
TI  - Corrigendum to "Routine preoperative brain CT in resectable non-small cell lung
      cancer-Ten years experience from a tertiary UK thoracic center" [Lung Cancer 122
      (August) (2018) 195-199].

PMID- 30287082
TI  - Diagnostic application of recombinant Leishmania proteins and evaluation of their
      in vitro immunogenicity after stimulation of immune cells collected from
      tegumentary leishmaniasis patients and healthy individuals.
AB  - The present study evaluated the cytokine profile in PBMC supernatants and the
      humoral response in mucosal leishmaniasis (ML) patients and in healthy subjects
      living in an endemic area. Four proteins, which had previously proven to be
      antigenic in the human disease, were tested: LiHyM, enolase, eukaryotic
      initiation factor 5a, and Beta-tubulin. Results showed that all of the proteins
      stimulated human cells with higher IFN-gamma and lower IL-4 and IL-10 levels. The
      analysis of antibody isotypes correlated with cell response, since the IgG2
      production was higher than IgG1 in both groups. By contrast, a Th2 response was
      found when an antigenic Leishmania extract was used. Serological analyses
      revealed high sensitivity and specificity values for the serodiagnosis of the
      disease, when compared to the data obtained using the antigenic preparation. In
      conclusion, this study presents new candidates to be evaluated as biomarkers in
      tegumentary leishmaniasis.

PMID- 30287083
TI  - Virtual reality exposure therapy for anxiety and related disorders: A meta
      analysis of randomized controlled trials.
AB  - Trials of virtual reality exposure therapy (VRET) for anxiety-related disorders
      have proliferated in number and diversity since our previous meta-analysis that
      examined 13 total trials, most of which were for specific phobias (Powers &
      Emmelkamp, 2008). Since then, new trials have compared VRET to more diverse
      anxiety and related disorders including social anxiety disorder (SAD),
      posttraumatic stress disorder (PTSD), and panic disorder (PD) with and without
      agoraphobia. With the availability of this data, it is imperative to re-examine
      the efficacy of VRET for anxiety. A literature search for randomized controlled
      trials of VRET versus control or in vivo exposure yielded 30 studies with 1057
      participants. Fourteen studies tested VRET for specific phobias, 8 for SAD or
      performance anxiety, 5 for PTSD, and 3 for PD. A random effects analysis
      estimated a large effect size for VRET versus waitlist (g = 0.90) and a medium to
      large effect size for VRET versus psychological placebo conditions (g = 0.78). A
      comparison of VRET and in vivo conditions did not show significantly different
      effect sizes (g = -0.07). These findings were relatively consistent across
      disorders. A meta-regression analysis revealed that larger sample sizes were
      associated with lower effect sizes in VRET versus control comparisons (beta = 
      0.007, p <  0.05). These results indicate that VRET is an effective and equal
      medium for exposure therapy.

PMID- 30287084
TI  - An Inconvenient Truth: Calcium Sensors Are Calcium Buffers.
AB  - Recent advances in Ca2+ imaging have given neuroscientists a tool to follow the
      activity of large numbers of individual neurons simultaneously in vivo in the
      brains of animals as they are presented with sensory stimulation, respond to
      environmental challenges, and engage in behaviors. The Ca2+ sensors used to
      transduce changes in cellular Ca2+ into changes in fluorescence must bind Ca2+ to
      produce a signal. By binding Ca2+, these sensors can act as buffers, often
      reducing the magnitude of a Ca2+ change severalfold, and producing a proportional
      slowing of the rates of change. Ca2+ probes can thus distort the patterns of
      activity they are intended to study and modify ongoing Ca2+ signaling functions.
      Recognizing these factors will enhance the use of in vivo Ca2+ imaging in the
      investigation of neural circuit function.

PMID- 30287086
TI  - [We can call hiper frequent users to the patients with the highest number of
      attention in emergencies and primary care].

PMID- 30287085
TI  - Anti-osteoclastic effects of C-glucosidic ellagitannins mediated by actin
      perturbation.
AB  - Actin subunits assemble into actin filaments whose dynamics and three-dimensional
      architectures are further regulated by a variety of cellular factors to establish
      the functional actin cytoskeleton. The C-glucosidic ellagitannin vescalagin and
      its simpler analogue vescalin, affect both the dynamics and the ultrastructure of
      the actin cytoskeleton by directly binding to F-actin. Herein, we show that in
      vitro, the two compounds induce the formation of distinct F-actin networks
      characterized by different superstructures and dynamics. In living mature
      osteoclasts, highly specialized bone-degrading cells that constantly remodel
      their cytoskeleton, vescalagin and vescalin alter actin dynamics at podosomes and
      compromise the integrity of the podosome belt that forms the bone-degrading
      apparatus. Both compounds target the bone-resorbing activity at concentrations
      that preserve osteoclastic maturation and survival and with no detectable impact
      on the behaviour of bone-forming osteoblastic cells. This anti-osteoclastic
      activity of vescalagin and vescalin reveals the potential of targeting actin
      dynamics as a new therapeutic opportunity and, in this case, as a plausible
      approach for the local treatment of osteoporosis.

PMID- 30287087
TI  - Traumatic coagulopathies.

PMID- 30287089
TI  - Intensivists, lose all hope.

PMID- 30287088
TI  - Complications during intra-hospital transport of pediatric patient on
      extracorporeal membrane oxygenation.

PMID- 30287090
TI  - N-terminal transactivation function, AF-1, of estrogen receptor alpha controls
      obesity through enhancement of energy expenditure.
AB  - OBJECTIVE: Studies using the estrogen receptor alpha (ERalpha) knock-out
      (alphaERKO) mice have demonstrated that ERalpha plays a crucial role in various
      estrogen-mediated metabolic regulations. ERalpha is a ligand dependent
      transcription regulator and its activity is regulated by estrogenic compounds.
      ERalpha consists of two transcriptional activation domains, AF-1 and AF-2. The
      activities of these domains are regulated through different mechanisms; however,
      the specific physiological role in metabolic regulation by these domains is still
      unclear. METHODS: We utilized an ERalpha AF-2 mutant knock-in mouse (AF2ERKI) to
      evaluate the physiological functionality of ERalpha transactivation domains. Due
      to the estrogen insensitive AF-2 mutation, the phenotypes of AF2ERKI mice are
      seemingly identical to the global alphaERKO including obesity in the females.
      Distinct from the alphaERKO, the AF-1 function of AF2ERKI mice can be activated
      by tamoxifen (Tam). Ovariectomized (OVX) AF2ERKI and WT females were treated with
      Tam and fed a high-fat diet (HFD) for 10 weeks. Additionally, indirect
      calorimetric analysis was performed using metabolic chambers with food intake and
      locomotor activity recorded for Tam-treated AF2ERKI and alphaERKO females.
      RESULTS: Obesity in HFD-fed AF2ERKI females was prevented by Tam treatment;
      particularly, inguinal fat accumulation was strongly blocked by Tam treatment.
      Alterations in fat metabolism genes, however, were not found in either inguinal
      fat nor visceral fat to be Tam-regulated, even though fat accumulation was
      strongly reduced by Tam treatment. Indirect calorimetric analysis revealed that
      without alteration of food intake and locomotor activity Tam treatment increased
      energy expenditure in AF2ERKI but not alphaERKO females. CONCLUSIONS: These
      results suggest that the activation of ERalpha AF-1 prevents fat accumulation.
      The prevention of obesity through AF-1 is mediated by induction of energy
      expenditure rather than ERalpha AF-1 functionality of lipid metabolism gene
      regulation in fat tissues.

PMID- 30287091
TI  - Compensatory mechanisms for methylglyoxal detoxification in experimental &
      clinical diabetes.
AB  - OBJECTIVES: The deficit of Glyoxalase I (Glo1) and the subsequent increase in
      methylglyoxal (MG) has been reported to be one the five mechanisms by which
      hyperglycemia causes diabetic late complications. Aldo-keto reductases (AKR) have
      been shown to metabolize MG; however, the relative contribution of this
      superfamily to the detoxification of MG in vivo, particularly within the diabetic
      state, remains unknown. METHODS: CRISPR/Cas9-mediated genome editing was used to
      generate a Glo1 knock-out (Glo1-/-) mouse line. Streptozotocin was then applied
      to investigate metabolic changes under hyperglycemic conditions. RESULTS: Glo1-/-
      mice were viable and showed no elevated MG or MG-H1 levels under hyperglycemic
      conditions. It was subsequently found that the enzymatic efficiency of various
      oxidoreductases in the liver and kidney towards MG were increased in the Glo1-/-
      mice. The functional relevance of this was supported by the altered distribution
      of alternative detoxification products. Furthermore, it was shown that MG
      dependent AKR activity is a potentially clinical relevant pathway in human
      patients suffering from diabetes. CONCLUSIONS: These data suggest that in the
      absence of GLO1, AKR can effectively compensate to prevent the accumulation of
      MG. The combination of metabolic, enzymatic, and genetic factors, therefore, may
      provide a better means of identifying patients who are at risk for the
      development of late complications caused by elevated levels of MG.

PMID- 30287092
TI  - Corrections.

PMID- 30287093
TI  - Nuclear Factor One X in Development and Disease.
AB  - The past decade has seen incredible advances in the field of stem cell biology
      that have greatly improved our understanding of development and provided
      important insights into pathological processes. Transcription factors (TFs) play
      a central role in mediating stem cell proliferation, quiescence, and
      differentiation. One TF that contributes to these processes is Nuclear Factor One
      X (NFIX). Recently, NFIX activity has been shown to be essential in multiple
      organ systems and to have important translational impacts for human health. Here,
      we describe recent studies showing the contribution of NFIX to muscle development
      and muscular dystrophies, hematopoiesis, cancer, and neural stem cell biology,
      highlighting the importance of this knowledge in the development of therapeutic
      targets.

PMID- 30287094
TI  - Immunohistochemical expression analysis of the human fetal lower urogenital
      tract.
AB  - We have studied the ontogeny of the developing human male and female urogenital
      tracts from 9 weeks (indifferent stage) to 16 weeks (advanced sex
      differentiation) of gestation by immunohistochemistry on mid-sagittal sections.
      Sixteen human fetal pelvises were serial sectioned in the sagittal plane and
      stained with antibodies to epithelial, muscle, nerve, proliferation and hormone
      receptor markers. Key findings are: (1) The corpus cavernosum in males and
      females extends into the glans penis and clitoris, respectively, during the
      ambisexual stage (9 weeks) and thus appears to be an androgen-independent event.
      (2) The entire human male (and female) urethra is endodermal in origin based on
      the presence of FOXA1, KRT 7, uroplakin, and the absence of KRT10 staining. The
      endoderm of the urethra interfaces with ectodermal epidermis at the site of the
      urethral meatus. (3) The surface epithelium of the verumontanum is endodermal in
      origin (FOXA1-positive) with a possible contribution of Pax2-positive epithelial
      cells implying additional input from the Wolffian duct epithelium. (4) Prostatic
      ducts arise from the endodermal (FOXA1-positive) urogenital sinus epithelium near
      the verumontanum. (5) Immunohistochemical staining of mid-sagittal and para
      sagittal sections revealed the external anal sphincter, levator ani,
      bulbospongiosus muscle and the anatomic relationships between these developing
      skeletal muscles and organs of the male and female reproductive tracts. Future
      studies of normal human developmental anatomy will lay the foundation for
      understanding congenital anomalies of the lower urogenital tract.

PMID- 30287095
TI  - Corrigendum to "Outcomes and healthcare-associated costs one year after intensive
      care-treated cardiac arrest" [Resuscitation 131 (2018) 128-134].

PMID- 30287096
TI  - Wake-up Sleepy Gene: Reactivating Fetal Globin for beta-Hemoglobinopathies.
AB  - Disorders in hemoglobin (hemoglobinopathies) were the first monogenic diseases to
      be characterized and remain among the most common and best understood genetic
      conditions. Moreover, the study of the beta-globin locus provides a textbook
      example of developmental gene regulation. The fetal gamma-globin genes
      (HBG1/HBG2) are ordinarily silenced around birth, whereupon their expression is
      replaced by the adult beta-globin genes (HBB primarily and HBD). Over 50 years
      ago it was recognized that mutations that cause lifelong persistence of fetal
      gamma-globin expression ameliorate the debilitating effects of mutations in beta
      globin. Since then, research has focused on therapeutically reactivating the
      fetal gamma-globin genes. Here, we summarize recent discoveries, focusing on the
      influence of genome editing technologies, including CRISPR-Cas9, and emerging
      gene therapy approaches.

PMID- 30287097
TI  - Carbon dioxide in office diagnostic hysteroscopy: An open question. A multicenter
      randomized trial on 1982 procedures.
AB  - OBJECTIVE: to compare carbon dioxide and saline solution distension in diagnostic
      hysteroscopies with regards to patient discomfort and procedural time and in
      accordance with the instrument diameter (5 mm vs 3.5 mm). The secondary outcome
      was to evaluate the role of the patient age and the obstetrical history on
      perception of pain and procedural time. STUDY DESIGN: This is a prospective
      multicenter randomized study including 1982 patients that underwent office
      diagnostic hysteroscopy in: Policlinico Abano Terme, Universita Cattolica del
      Sacro Cuore in Rome and Ente Ecclesiastico Ospedale Generale Regionale "F.
      Miulli" in Acquaviva delle Fonti. They were firstly randomized according to
      distension medium and secondly according to instrument diameter. Pain perception
      after the procedure was assessed by VAS (Visual Analogue Scale) score and
      procedural time was registered. Mann-Whitney U test was used to compare data.
      RESULTS: Lower pain score and procedural time were recorded with the employment
      of Carbon Dioxide (p < 001). Patient discomfort and procedural time were
      significantly influenced by the instrument diameter independent of the distension
      medium used, though in the subgroup where gas was employed VAS score after 1 min
      (VAS1) resulted lower compared to saline solution in both the traditional and
      mini-hysteroscopy procedures (p < 001). CONCLUSION: Carbon dioxide and saline
      solution are both suitable distension media for outpatient diagnostic
      hysteroscopy; nonetheless, carbon dioxide confers advantages in terms of pain
      perception and procedural time.

PMID- 30287098
TI  - The role of neoadjuvant chemotherapy or chemoradiotherapy for advanced
      gallbladder cancer - A systematic review.
AB  - BACKGROUND: Neoadjuvant chemotherapy for advanced gallbladder cancer (GBC) has
      recently been proposed as an alternative to adjuvant chemotherapy, with potential
      increase in resectability rate and overall survival. AIM: To undertake a
      systematic review and critical appraisal of available literature on the use of
      neoadjuvant chemotherapy (NACT) or chemoradiotherapy (NACRT) in the treatment of
      advanced GBC. METHODS: Systematic review carried out in line with the Meta
      analysis Of Observational Studies in Epidemiology guidelines. Primary outcomes
      were clinical benefit rate (CBR) of neoadjuvant therapy, defined as percentage of
      complete response, partial response and stable disease, resectability rate and R0
      resection. Secondary outcomes were overall and disease-free survival. RESULTS: 8
      studies met the inclusion criteria (n = 474), of which 398 (84.0%) received NACT
      and 76 (16.0%) received NACRT. 133 of 434 patients (30.6%) had progressive
      disease despite NACT or NACRT. The CBR was 66.6%. 17% of the patients who
      responded to chemotherapy did not proceed to surgery. 50.4% of the patients were
      considered suitable for surgical resection, of which 191 (40.3%) underwent
      curative resection. The R0 rate for the whole cohort was 35.4%. Overall survival
      ranged from 18.5 to 50.1 months for those who underwent curative resection versus
      5.0-10.8 months for non-resected group. CONCLUSIONS: There is insufficient data
      to support the routine use of NACT or NACRT in advanced GBC, as this has only
      benefited a third of whole cohort, who eventually achieved a R0 resection. Future
      studies should be in the form of randomized controlled trials to investigate the
      role of neoadjuvant therapy in advanced GBC.

PMID- 30287099
TI  - Variations in Hook of Hamate Morphology: A Cadaveric Analysis.
AB  - PURPOSE: The hook of the hamate is an anatomical structure that separates the
      ulnar border of the carpal tunnel from Guyon's canal and serves as a landmark for
      surgeons. The hook of the hamate is also subject to fracture from injury. We
      hypothesize that there are variations in the hook of the hamate in the general
      population. METHODS: One thousand pairs of hamates (2,000 hamates) from the
      Hamann-Todd Collection at the Cleveland Natural History Museum were analyzed. The
      height of the hook of the hamate and the total height of the hamate bone were
      measured using digital calipers. The hook height ratio was defined as the hook
      height divided by the total height of the hamate. Statistical analysis was
      performed using unpaired Student's t test to determine differences in sex and
      race. RESULTS: The mean hook height was 9.8 +/- 1.4 mm (range, 2.5-15.9 mm),
      whereas the mean hook height ratio was 0.42 +/- 0.04 (range, 0.15-0.56). There
      was a 3.1% (62/2,000) incidence of abnormally small hooks, which we classified as
      hypoplastic and aplastic. Of the hypoplastic hooks, 55% (24/44) were bilateral,
      whereas 44% (8/18) of the aplastic hooks were bilateral. The incidence of
      variation in size in the hook of the hamate was highest in white females (9.3%)
      and lowest in black males (1.4%). CONCLUSIONS: Abnormalities in hook of hamate
      anatomy are common in the general population, especially in white females.
      CLINICAL RELEVANCE: Knowledge of anatomic variation in the hook of the hamate may
      provide additional insight into surgeons' palpation of bony anatomy,
      interpretation of imaging studies, and use of the hook as a landmark during
      surgery.

PMID- 30287100
TI  - Management of the Posttraumatic Coronoid-Deficient Elbow.
AB  - Posttraumatic coronoid deficiency is one of the most challenging scenarios even
      for the most experienced elbow surgeon. Surgical options can be grouped into soft
      tissue reconstructions, autogenous corticocancellous bone graft reconstructions,
      osteochondral reconstructions, and prosthetic replacement. However, the
      literature is inconclusive with limited cases, short follow-up, and no conclusive
      clinical comparative studies of these techniques. This article provides a review
      of the current surgical options, and we offer the senior author's (S.W.O.)
      perspective after years of experience with many of these techniques.

PMID- 30287101
TI  - Absence of the Pronator Quadratus Muscle Precluding Distal Nerve Transfer.
AB  - The branch of the anterior interosseous nerve to the pronator quadratus (PQ) is
      increasingly used as a donor nerve for end-to-end and reverse end-to-side nerve
      transfers. The anatomy of the PQ (and its nerve branch) is generally considered
      reliable in the absence of prior trauma. In this report, we describe a patient
      with an absent PQ despite intact clinical examination of other muscles supplied
      by the anterior interosseous nerve. The absence of the PQ precluded the use of
      its nerve as a donor nerve for transfer.

PMID- 30287102
TI  - Epidemiology and determinants of type 2 diabetes in south Asia.
AB  - Type 2 diabetes has rapidly developed into a major public health problem in south
      Asia (defined here as Bangladesh, Bhutan, India, Nepal, Pakistan, and Sri Lanka)
      in recent decades. During this period, major lifestyle changes associated with
      economic transition, industrialisation, urbanisation, and globalisation have been
      key determinants in the increasing burden of non-communicable diseases. A decline
      in nutrition quality, reduced physical activity, and increased sedentary
      behaviours are reflected in the increasing prevalence of type 2 diabetes and
      related risk factors in the region. The International Diabetes Federation 2017
      estimates of the prevalence of diabetes in adults in the region range from 4.0%
      in Nepal to 8.8% in India. The prevalence of overweight ranges from 16.7% in
      Nepal to 26.1% in Sri Lanka, and the prevalence of obesity ranges from 2.9% in
      Nepal to 6.8% in Sri Lanka. An increasing proportion of children, adolescents,
      and women are overweight or obese, leading to a heightened risk of type 2
      diabetes. Ethnic south Asians present with greater metabolic risk at lower levels
      of BMI compared with other ethnic groups (referred to as the south Asian
      phenotype), with type 2 diabetes often developing at a younger age, and with
      rapid progression of diabetic complications. Because of the presence of multiple
      risk factors and a body composition conducive to the development of type 2
      diabetes, south Asians should be aggressively targeted for prevention. In this
      Series paper, we detail trends in the prevalence of diabetes in the region and
      address major determinants of the disease in the context of nutrition and
      physical activity transitions and the south Asian phenotype.

PMID- 30287103
TI  - Clinical management of type 2 diabetes in south Asia.
AB  - Compared with other ethnic groups, south Asian people with type 2 diabetes tend
      to develop the disease at a younger age and manifest with higher glycaemia,
      dyslipidaemia, nephropathy, and cardiovascular diseases. Additionally, specific
      issues that can affect treatment of type 2 diabetes in south Asia include poor
      awareness of the disease, delay in diagnosis, inadequate treatment, the use of
      ineffective and often harmful alternative medicines, and frequent non-compliance
      with lifestyle recommendations and drug treatment. Disease development at younger
      ages, delayed diagnosis, and inadequate management result in early development of
      severe complications and premature mortality. In this Series paper, we describe
      the challenges associated with the increasing burden of type 2 diabetes in south
      Asia and discuss ways to improve clinical care of people with the disorder in the
      region (defined to include Bangladesh, Bhutan, India, Nepal, Pakistan, and Sri
      Lanka). Treatment of diabetes in south Asia needs to be individualised on the
      basis of diverse and heterogeneous lifestyle, phenotype, environmental, social,
      cultural, and economic factors. Aggressive management of risk factors from
      diagnosis is necessary to reduce the risk of microvascular and macrovascular
      complications, focusing on provision of basic treatments (eg, metformin, low-cost
      statins, and blood pressure-lowering drugs) and other interventions such as
      smoking cessation. Strengthening of the primary care model of care, better
      referral linkages, and implementation of rehabilitation services to care for
      patients with chronic complications will be important. Finally, improvement of
      physicians' skills, provision of relevant training to non-physician health-care
      workers, and the development and regular updating of national clinical management
      guidelines will also be crucial to improve diabetes care in the region.

PMID- 30287104
TI  - Public health and health systems: implications for the prevention and management
      of type 2 diabetes in south Asia.
AB  - Many non-communicable chronic diseases, including type 2 diabetes, are highly
      prevalent, costly, and largely preventable. The prevention and management of type
      2 diabetes in south Asia requires a combination of lifestyle changes and long
      term health-care management. However, public health and health-care systems in
      south Asian countries face serious challenges, including the need to provide
      services to many people with inadequate resources, and substantial between
      population and within-population inequalities. In this Series paper, we explore
      the importance and particular challenges of public health and health systems in
      south Asian countries (Bangladesh, Bhutan, India, Nepal, Pakistan, and Sri Lanka)
      with respect to the provision of culturally appropriate lifestyle modification to
      prevent and manage diabetes, especially in resource-poor settings. Effective
      primary prevention strategies are urgently needed to counter risk factors and
      behaviours preconception, in utero, in infancy, and during childhood and
      adolescence. A concerted focus on education, training, and capacity building at
      the community level would ensure the more widespread use of non-physician care,
      including community health workers. Major investment from governments and other
      sources will be essential to achieve substantial improvements in the prevention
      and management of type 2 diabetes in the region.

PMID- 30287105
TI  - Editorial.

PMID- 30287106
TI  - Ultrasound-guided versus blind temporomandibular joint injections: a pilot
      cadaveric evaluation.
AB  - Temporomandibular disorders are painful conditions that require precise injection
      therapy in selected patients. This pilot cadaveric study was undertaken to
      compare the accuracy of temporomandibular joint (TMJ) injection between the
      anatomical landmark-based (blind) technique and an ultrasound-guided technique.
      TMJ injections using the blind technique or the ultrasound-guided technique were
      performed in 10 non-embalmed cadavers. After dissection, the accuracy of the TMJ
      injections was found to be significantly greater for the ultrasound-guided
      injections than for the blind technique (blind 55% vs. ultrasound 95%, P=0.008).
      For injections into the upper joint space of the TMJ, the success rate of the
      injection was comparable for the two techniques (blind 80% vs. ultrasound 100%,
      P=0.474). However, ultrasound-guided injections into the lower joint space had a
      much higher success rate than the blind technique (blind 30% vs. ultrasound 90%,
      P=0.020). The blind technique was associated with a considerable proportion of
      failed or inappropriate injections, especially for lower joint space injections.
      Ultrasound-guided TMJ injections were accomplished with a higher accuracy than
      the conventional blind technique, especially in the case of injections targeting
      the lower joint space of the TMJ.

PMID- 30287107
TI  - Direct percutaneous puncture digital-subtraction-angiography-based classification
      and treatment selection for soft-tissue arteriovenous malformations of
      maxillofacial region: a retrospective study.
AB  - Treatment of arteriovenous malformations (AVMs) should be individualized based on
      the imaging findings. A total of 117 AVM cases were categorized into three types
      based on the angio-architectural characteristics: Type I (n=14, no draining vein
      or diameter of the draining vein <2mm); Type II (n=64, draining vein diameter 2
      6mm); and Type III (n=39, draining vein diameter >6mm). Subjects were randomly
      allocated to one of two treatment groups: Group A (n=59) received multipoint
      percutaneous ethanol injection (MPEI), while Group B (n=58) received super
      selective angiograms followed by embolization with gelfoam (EFAG) plus MPEI.
      Patients were followed up for 2-6 years. A significant between-group difference
      with respect to treatment outcomes was observed only for Type III cases (P<0.05).
      Direct percutaneous puncture digital-subtraction-angiography-guided
      classification of AVMs provides easy-to-follow guidelines for its clinical
      management. EFAG plus MPEI with reduced procedure time and the amount of ethanol
      should be used for Type III AVMs.

PMID- 30287108
TI  - "Feeling confident and equipped": Evaluating the acceptability and efficacy of an
      overdose response and naloxone administration intervention to service industry
      employees in New York City.
AB  - BACKGROUND: The problem of injection drug use in public bathrooms has been
      documented from the perspectives of people who inject drugs and service industry
      employees (SIEs). Previous studies suggest that SIEs are unaware of how to
      respond to opioid overdoses, yet there are no behavioral interventions designed
      for SIEs to address their specific needs. In response to this gap in the field,
      we constructed, implemented, and evaluated a three-module behavioral intervention
      for SIEs grounded in the Information-Motivation-Behavioral skills model. This
      paper focuses on the evaluation of one module, namely, the intervention component
      addressing overdose response and naloxone administration (ORNA). METHODS:
      Participants were SIEs (N = 18 from two separate business establishments)
      recruited using convenience sampling. The study utilized a pre-/post-test
      concurrent nested mixed method design and collected quantitative and qualitative
      data including an evaluation of the intervention module. The primary outcomes
      were opioid overdose-related knowledge and attitudes. Acceptability was also
      assessed. RESULTS: SIEs demonstrated significant improvements (p <  0.01, Cohen's
      d = 1.45) in opioid overdose-related knowledge as well as more positive opioid
      overdose-related attitudes (p< 0.01, Cohen's d = 2.45) following the
      intervention. Participants also reported high levels of acceptability of the
      module and suggestions for improvement (i.e., more role-playing). CONCLUSIONS:
      This study highlights the acceptability and evidence of efficacy of the ORNA
      module, as well as the utility of training SIEs in ORNA. The expansion of this
      training to other SIEs and public employees (librarians, etc.) who manage public
      bathrooms warrants further investigation.

PMID- 30287109
TI  - [Evaluation of surgical practice in the treatment of lung cancer in France from
      the PMSI national database].
AB  - BACKGROUND: In recent years, improving the quality of care has been a concern for
      health professionals in France, through the certification of institutions,
      accreditation and continuous professional development. Evaluation of these
      different measures has rarely been carried out. The objective of the study was to
      evaluate the quality of surgical management of lung cancer in different regions
      using hospital mortality as an indicator. METHOD: From the national database of
      the Program of Medical Information Systems (PMSI), data on all patients who had
      undergone surgery for lung cancer were extracted as well as the characteristics
      of the centers. The main outcome criterion was hospital mortality. Logistic
      models allowed an estimation of the risk standardized mortality rate for each
      center. RESULTS: From January 1, 2015 to December 31, 2015, 10,675 patients
      underwent surgery for lung cancer in 158 French centers. The hospital mortality
      rate was 3.43% (n=366). Thirty-nine facilities (25%) performed fewer than 15
      pulmonary resections. The minimum activity volume was a single pulmonary
      resection during the year and the maximum was 300 interventions with a
      coefficient of variation estimated at 147%. Hospital mortality ranged from 0 % to
      50% depending on the entries with a coefficient of variation of 112%. For some
      regions, it is possible to count up to 5 centers per million inhabitants
      (Languedoc-Roussillon) or 4 centers per million inhabitants (Limousin, Pays-de
      Loire). The majority of regions had 3 centers per million inhabitants. Eleven
      regions have no centers with a standardized mortality rate below 3%. Five regions
      (Languedoc-Roussillon, Pays-de-Loire, Aquitaine, Brittany and Provence Alpes Cote
      d'Azur) have at least two centers with a risk standardized rate of mortality
      above 4%. Among the academic centers, 20% have a risk standardized mortality rate
      of less than 3%. Among the centers with a risk standardized rate of mortality<3%,
      20% performed more than 39 pulmonary resections, 7% between 39 and 15 procedures
      and 0% for centers with<15 interventions. CONCLUSION: This work confirms that
      hospital volume is one of the components of quality of care. The number of
      centers should be adapted to the actual needs of the population in order to
      enable patients to access effective services.

PMID- 30287111
TI  - Internal Tensile Force and A2 Domain Unfolding of von Willebrand Factor Multimers
      in Shear Flow.
AB  - Using Brownian molecular dynamics simulations, we examine the internal dynamics
      and biomechanical response of von Willebrand factor (vWF) multimers subject to
      shear flow. The coarse grain multimer description employed here is based on a
      monomer model in which the A2 domain of vWF is explicitly represented by a
      nonlinear elastic spring whose mechanical response was fit to experimental
      force/extension data from vWF monomers. This permits examination of the dynamic
      behavior of hydrodynamic forces acting on A2 domains as a function of shear rate
      and multimer length, as well as position of an A2 domain along the multimer
      contour. Force/position data reveal that collapsed multimers exhibit a force
      distribution with two peaks, one near each end of the chain; unraveled multimers,
      however, show a single peak in A2 domain force near the center of multimers.
      Guided further by experimental data, significant excursions of force acting on a
      domain are associated with an increasing probability for A2 domain unfolding. Our
      results suggest that the threshold shear rate required to induce A2 domain
      unfolding is inversely proportional to multimer length. By examining data for the
      duration and location of significant force excursions, convincing evidence is
      advanced that unfolding of A2 domains, and therefore scission of vWF multimers by
      the size-regulating blood enzyme ADAMTS13, happen preferentially near the center
      of unraveled multimers.

PMID- 30287110
TI  - The Role of Lipid Interactions in Simulations of the alpha-Hemolysin Ion-Channel
      Forming Toxin.
AB  - Molecular dynamics simulations were performed to describe the function of the ion
      channel-forming toxin alpha-hemolysin (alphaHL) in lipid membranes that were
      composed of either 1,2-diphytanoyl-sn-glycero-3-phospho-choline or 1-palmitoyl-2
      oleoyl-sn-glycero-3-phospho-choline. The simulations highlight the importance of
      lipid type in maintaining alphaHL structure and function, enabling direct
      comparison to experiments for biosensing applications. We determined that
      although the two lipids studied are similar in structure, 1,2-diphytanoyl-sn
      glycero-3-phospho-choline membranes better match the hydrophobic thickness of
      alphaHL compared to 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-choline membranes.
      This hydrophobic match is essential to maintaining proper alignment of beta-sheet
      loops at the trans entrance of alphaHL, which, when disrupted, creates an
      additional constriction to ion flow that decreases the channel current below
      experimental values and creates greater variability in channel conductance.
      Agreement with experiments was further improved with sufficient lipid membrane
      equilibration and allowed the discrimination of subtle alphaHL conduction states
      with lipid type. Finally, we explore the effects of truncating the extramembrane
      cap of alphaHL and its role in maintaining proper alignment of alphaHL in the
      membrane and channel conductance. Our results demonstrate the essential role of
      lipid type and lipid-protein interactions in simulations of alphaHL and will
      considerably improve the interpretation of experimental data.

PMID- 30287113
TI  - Childhood conditions and productive aging in China.
AB  - We investigate the impacts of childhood conditions on productive aging in China.
      Productive aging is defined as engagement in working, caring, and socially
      productive activities (volunteering, informal helping, etc.). Two theoretical
      frameworks are examined: (1) the pathway model that emphasizes later life health
      and socioeconomic conditions are related to dis(advantages) starting from
      childhood, and (2) the latency model that illustrates childhood experiences
      directly affect productive engagement due to biomedical influences or values and
      preferences formed during childhood. The 2011, 2013 and 2014 China Health and
      Retirement Longitudinal Studies (CHARLS) were used as these data sets provide
      both contemporaneous and retrospective information. The analytic sample consists
      of 5818 respondents aged 55 and above. We conduct multilevel analyses and path
      models to estimate the effects of childhood conditions, including family
      background (hukou - household registration - status and parents' education),
      neighborhood cohesion, subjective health and nutrition. Individual and family
      contemporaneous characteristics and clustered data structure were controlled for.
      The results largely support a pathway model in that childhood health and
      nutrition affect the likelihood of productive activities in later life through
      their influence on cognition and disabilities in old age. Moreover, family
      background and neighborhood cohesion are associated with productive activities
      via the effects through mid-life work, later life cognition, and disabilities.
      Results also provide some support for the latency model through the direct effect
      of neighborhood cohesion on socially productive activities, highlighting the
      importance of values formed in early life in shaping the motivations of
      productive engagement in later life. To conclude, we demonstrate that better
      childhood health, an advantaged family background, and values of helping others
      instilled in childhood affect older adults' productive engagement. Policies
      should be put in place to reduce socioeconomic disadvantages in childhood and
      also to cultivate cohesive community environments.

PMID- 30287112
TI  - Prediction of the Closed Conformation and Insights into the Mechanism of the
      Membrane Enzyme LpxR.
AB  - Covalent modification of outer membrane lipids of Gram-negative bacteria can
      impact the ability of the bacterium to develop resistance to antibiotics as well
      as modulating the immune response of the host. The enzyme LpxR from Salmonella
      typhimurium is known to deacylate lipopolysaccharide molecules of the outer
      membrane; however, the mechanism of action is unknown. Here, we employ molecular
      dynamics and Monte Carlo simulations to study the conformational dynamics and
      substrate binding of LpxR in representative outer membrane models as well as
      detergent micelles. We examine the roles of conserved residues and provide an
      understanding of how LpxR binds its substrate. Our simulations predict that the
      catalytic H122 must be Nepsilon-protonated for a single water molecule to occupy
      the space between it and the scissile bond, with a free binding energy of -8.5
      kcal mol-1. Furthermore, simulations of the protein within a micelle enable us to
      predict the structure of the putative "closed" protein. Our results highlight the
      need for including dynamics, a representative environment, and the consideration
      of multiple tautomeric and rotameric states of key residues in mechanistic
      studies; static structures alone do not tell the full story.

PMID- 30287114
TI  - Diverse socioeconomic processes influencing health and wellbeing across
      generations in deprived neighbourhoods in Malta.
AB  - This study contributes to the geography of health by emphasising
      intergenerational differences in health determinants in a Mediterranean context.
      Using a grounded theory approach, it aims to explore the intergenerational
      processes between parents and children and their impact on determinants of health
      and wellbeing by focusing on the neighbourhood processes, including human, social
      and cultural capital in their neighbourhood. Through structured in-depth
      interviews with parents and children coming from two deprived neighbourhoods in
      Malta, it was shown that what may be considered valuable and beneficial for the
      adults' wellbeing may be detrimental for their children. In other cases, the
      neighbourhood processes that are being experienced negatively by adults seem to
      be beneficial for the health and wellbeing of young people. Thus the
      neighbourhood does not influence the inhabitants of different age groups in a
      homogenous and consistent manner. Indeed, the experiences of adults and children,
      even though they belong to the same family and neighbourhood, may differ from
      each other. It also emerged that it is not only the parents who can influence
      determinants of a young person's wellbeing; children and adolescents are able to
      negotiate and contradict their parents' wishes and decisions in order to enjoy
      conditions that they find beneficial. This study therefore demonstrates how the
      processes related to the social determinants of health are not static but highly
      dynamic, even across generations.

PMID- 30287115
TI  - A unified ecological framework for studying effects of digital places on well
      being.
AB  - Social media has greatly expanded opportunities to study place and well-being
      through the availability of human expressions tagged with physical location. Such
      research often uses social media content to study how specific places in the
      offline world influence well-being without acknowledging that digital platforms
      (e.g., Twitter, Facebook, Youtube, Yelp) are designed in unique ways that
      structure certain types of interactions in online and offline worlds, which can
      influence place-making and well-being. To expand our understanding of the
      mechanisms that influence social media expressions about well-being, we describe
      an ecological framework of person-place interactions that asks, "at what broad
      levels of interaction with digital platforms and physical environments do effects
      on well-being manifest?" The person is at the centre of the ecological framework
      to recognize how people define and organize both digital and physical communities
      and interactions. The relevance of interactions in physical environments depends
      on the built and natural characteristics encountered across modes of activity
      (e.g., domestic, work, study). Here, social interactions are stratified into the
      meso-social (e.g., local social norms) and micro-social (e.g., personal
      conversations) levels. The relevance of interactions in digital platforms is
      contingent on specific hardware and software elements. Social interactions at the
      meso-social level include platform norms and passive use of social media, such as
      observing the expressions of others, whereas interactions at the micro-level
      include more active uses, like direct messaging. Digital platforms are accessed
      in a physical location, and physical locations are partly experienced through
      online interactions; therefore, interactions between these environments are also
      acknowledged. We conclude by discussing the strengths and limitations of applying
      the framework to studies of place and well-being.

PMID- 30287116
TI  - Surgical treatments for a case of superior canal dehiscence syndrome associated
      with patulous Eustachian tube.
AB  - OBJECTIVES: The patulous Eustachian tube (PET) and superior semicircular canal
      dehiscence syndrome (SCDS) have similarity in their symptoms and similar effects
      caused by positional changes, causing difficulty in the differentiation between
      the two disorders. This report describes a case of both SCDS and PET that was
      eventually successfully treated. METHODS: A 68-year-old man presented with
      hyperacusis to his own footsteps and gait disturbance. He had been diagnosed as
      PET two years before and had been treated by insertion of a silicone plug
      (Kobayashi plug) at the other hospital. Clinical case records, audiological data,
      cervical vestibular-evoked myogenic potential (cVEMP), Eustachian tube function
      tests and computed tomography (CT) were taken in the sitting position. RESULTS:
      While the CT confirmed superior semicircular canal dehiscence, the results of
      cVEMP was not typical of SCD likely due to preexisting hearing impairment in the
      right ear with a history of middle ear surgeries for the treatment of PET. He
      received round window reinforcement (RWR) and achieved relief from his symptoms
      but six months after the surgery, he visited again with complaints of autophony
      of his own voice and breathing. The tympanic membrane was found to move
      synchronous with respiration, and Eustachian tube function tests and the sitting
      CT confirmed the recurrence of severe PET. He had his silicone plug exchanged
      (increase in size of the Kobayashi plug) and achieved relief from symptoms.
      CONCLUSIONS: The present case was a rare instance showing that PET and SCDS can
      occur simultaneously in a patient. The patient achieved relief from symptoms
      after treatment with RWR and insertion of the Kobayashi plug.

PMID- 30287117
TI  - Simultaneous bilateral butterfly tympanoplasty using tragal cartilage from one
      ear.
AB  - OBJECTIVE: To evaluate the outcomes of simultaneous bilateral inlay butterfly
      cartilage tympanoplasties (BIBCT) using tragal cartilage from one ear in patients
      with bilateral chronic otitis media (BCOM). METHODS: 33 patients (66 ears) who
      underwent bilateral inlay butterfly cartilage tympanoplasties between June 2013
      and September 2016 in Department of Otolaryngology-Head and Neck Surgery of
      Adiyaman University Education and Research Hospital, Adiyaman, Turkey - a
      tertiary care university teaching hospital. Anatomical success and functional
      success were assessed postoperatively. Air-bone gap (ABG), air-conduction
      thresholds, and bone-conduction thresholds were all assessed. The preoperative
      and postoperative averages of 0.5, 1, 2, and 3kHz of pure-tone thresholds were
      used for the mean air- and bone-conduction thresholds according to the guidelines
      of the Committee on Hearing and Equilibrium. RESULTS: Anatomical success could be
      demonstrated in 57 of 66 ears (86.3%). The overall mean of ABG improved from
      23.97+/-8.63dB preoperatively to 10.42+/-4.82dB postoperatively (p<0.05). The ABG
      gain was 13.55+/-8.17dB. Postoperative percentages of patients with ABG less than
      20dB and 10dB were excellently achieved to 98% (41% preoperatively) and 56%
      (10.6% preoperatively), respectively. The average length of operation time for
      both ears was 57.42+/-9.39min. CONCLUSION: When compared with conventional two
      staged tympanoplasty in patients with BCOM, simultaneous BIBCT using tragal
      cartilage from one ear is an advantageous approach for multiple reasons which
      include single hospital stay with resultant decreased risk of complications
      associated with anesthesia and surgery, less morbidity like cosmetic and hearing
      discomfort, time-savingness and cost-effectiveness.

PMID- 30287118
TI  - Multiple inputs into a posterior-specific regulatory network in the Ciona
      notochord.
AB  - The gene regulatory networks underlying Ciona notochord fate specification and
      differentiation have been extensively investigated, but the regulatory basis for
      regionalized expression within the notochord is not understood. Here we identify
      three notochord-expressed genes, C11.331, C12.115 and C8.891, with strongly
      enriched expression in the secondary notochord cells at the posterior tip of the
      tail. C11.331 and C12.115 share a distinctive expression pattern that is highly
      enriched in the secondary notochord lineage but also graded within that lineage
      with the strongest expression at the posterior tip. Both genes show similar
      responses to pharmacological perturbations of Wnt and FGF signaling, consistent
      with an important role for Wnt and FGF ligands expressed at the tail tip.
      Reporter analysis indicates that the C11.331 cis-regulatory regions are
      extensively distributed, with multiple non-overlapping regions conferring
      posterior notochord-enriched expression. Fine-scale analysis of a minimal cis
      regulatory module identifies discrete positive and negative elements including a
      strong silencer. Truncation of the silencer region leads to increased expression
      in the primary notochord, indicating that C11.331 expression is influenced by
      putative regulators of primary versus secondary notochord fate. The minimal CRM
      contains predicted ETS, GATA, LMX and Myb sites, all of which lead to reduced
      expression in secondary notochord when mutated. These results show that the
      posterior-enriched notochord expression of C11.331 depends on multiple inputs,
      including Wnt and FGF signals from the tip of the tail, multiple notochord
      specific regulators, and yet-to-be identified regulators of regional identity
      within the notochord.

PMID- 30287120
TI  - Managing the Elderly Emergency Department Patient.

PMID- 30287119
TI  - Viewing their own seizures improves understanding of disease in people with
      epilepsy.
AB  - BACKGROUND: People with epilepsy (PWE) are frequently unable to recall the core
      manifestation of their disease, epileptic seizures. This limits their
      understanding of disease severity and social reactions to it. PURPOSE: The
      purpose of this study was to assess the effects of video presentation (VP) of
      one's own seizure and the role of seizure type/severity. METHODS: Ninety patients
      diagnosed with focal epilepsy undergoing diagnostic video-electroencephalography
      (EEG) monitoring were included. All participants were presented with a seizure of
      their predominant seizure type on videotape. Effects of viewing seizures were
      assessed using a questionnaire immediately after the VP (T1), after 3 days (T2),
      and after 3 months (T3). RESULTS: Of the participants, 97.6%, 87.2%, and 85.2%
      considered VP as helpful at T1, T2, and T3, respectively. Participants who viewed
      a more severe seizure tended to assess the VP as more helpful, related to an
      improved understanding of the disease and of reaction of others to their
      seizures. Of the participants, 11.5% and 5.0% perceived the VP as stressful at T2
      and T3, respectively. Severity of the presented seizure was positively correlated
      to the level of stress induced, mostly because of a feeling of helplessness based
      on ictal loss of control. CONCLUSIONS: The VP of the patients' own seizures is a
      way to improve the patients' knowledge on their disease, which was appreciated by
      the vast majority of participants. The VP of severe seizures was regarded more
      informative yet also more stressful. Further research is needed to examine
      possible effects on quality of life and compliance.

PMID- 30287121
TI  - Pneumothorax and Hemothorax in the Era of Frequent Chest Computed Tomography for
      the Evaluation of Adult Patients With Blunt Trauma.
AB  - STUDY OBJECTIVE: Although traditional teachings in regard to pneumothorax and
      hemothorax generally recommend chest tube placement and hospital admission, the
      increasing use of chest computed tomography (CT) in blunt trauma evaluation may
      detect more minor pneumothorax and hemothorax that might indicate a need to
      modify these traditional practices. We determine the incidence of pneumothorax
      and hemothorax observed on CT only and the incidence of isolated pneumothorax and
      hemothorax (pneumothorax and hemothorax occurring without other thoracic
      injuries), and describe the clinical implications of these injuries. METHODS:
      This was a planned secondary analysis of 2 prospective, observational studies of
      adult patients with blunt trauma, NEXUS Chest (January 2009 to December 2012) and
      NEXUS Chest CT (August 2011 to May 2014), set in 10 Level I US trauma centers.
      Participants' inclusion criteria were older than 14 years, presentation to the
      emergency department (ED) within 6 hours of blunt trauma, and receipt of chest
      imaging (chest radiograph, chest CT, or both) during their ED evaluation.
      Exposure(s) (for observational studies) were that patients had trauma and chest
      imaging. Primary measures and outcomes included the incidence of pneumothorax and
      hemothorax observed on CT only versus on both chest radiograph and chest CT, the
      incidence of isolated pneumothorax and hemothorax (pneumothorax and hemothorax
      occurring without other thoracic injuries), and admission rates, hospital length
      of stay, mortality, and frequency of chest tube placement for these injuries.
      RESULTS: Of 21,382 enrolled subjects, 1,064 (5%) had a pneumothorax and 384
      (1.8%) had a hemothorax. Of the 8,661 patients who received both a chest
      radiograph and a chest CT, 910 (10.5%) had a pneumothorax, with 609 (67%)
      observed on CT only; 319 (3.7%) had a hemothorax, with 254 (80%) observed on CT
      only. Of 1,117 patients with pneumothorax, hemothorax, or both, 108 (10%) had
      isolated pneumothorax or hemothorax. Patients with pneumothorax observed on CT
      only had a lower chest tube placement rate (30% versus 65%; difference in
      proportions [Delta] -35%; 95% confidence interval [CI] -28% to 42%), admission
      rate (94% versus 99%; Delta 5%; 95% CI 3% to 8%), and median length of stay (5
      versus 6 days; difference 1 day; 95% CI 0 to 2 days) but similar mortality
      compared with patients with pneumothorax observed on chest radiograph and CT.
      Patients with hemothorax observed on CT had only a lower chest tube placement
      rate (49% versus 68%; Delta -19%; 95% CI -31% to -5%) but similar admission rate,
      mortality, and median length of stay compared with patients with hemothorax
      observed on chest radiograph and CT. Compared with patients with other thoracic
      injury, those with isolated pneumothorax or hemothorax had a lower chest tube
      placement rate (20% versus 43%; Delta -22%; 95% CI -30% to -13%), median length
      of stay (4 versus 5 days; difference -1 day; 95% CI -3 to 1 days), and admission
      rate (44% versus 97%; Delta -53%; 95% CI -62% to -43%), with an admission rate
      comparable to that of patients without pneumothorax or hemothorax (49%).
      CONCLUSION: Under current imaging protocols for adult blunt trauma evaluation,
      most pneumothoraces and hemothoraces are observed on CT only and few occur as
      isolated thoracic injury. The clinical implications (admission rates and
      frequency of chest tube placement) of pneumothorax and hemothorax observed on CT
      only and isolated pneumothorax or hemothorax are lower than those of patients
      with pneumothorax and hemothorax observed on chest radiograph and CT and of those
      who have other thoracic injury, respectively.

PMID- 30287122
TI  - Waterfalls and Handoffs: A Novel Physician Staffing Model to Decrease Handoffs in
      a Pediatric Emergency Department.
AB  - STUDY OBJECTIVE: Patient handoffs at shift change in the emergency department
      (ED) are a well-known risk point for patient safety. Numerous methods have been
      implemented and studied to improve the quality of handoffs to mitigate this risk.
      However, few have investigated processes designed to decrease the number of
      handoffs. Our objective is to evaluate a novel attending physician staffing model
      in an academic pediatric ED that was designed to decrease patient handoffs.
      METHODS: A multidisciplinary team met in August 2012 to redesign the attending
      physician staffing model. The team sought to decrease patient handoffs, optimize
      provider efficiency, and balance workload without increasing total attending
      physician hours. The original model required multiple handoffs at shift change.
      This was replaced with overlapping "waterfall" shifts. This was a retrospective
      quality improvement study of a process change that evaluated the percentage of
      intradepartmental handoffs before and after implementation of a new novel
      attending physician staffing model. In addition, surveys were conducted among
      attending physicians and charge nurses to inquire about perceived impacts of the
      change. RESULTS: A total of 43,835 patient encounters were analyzed. Immediately
      after implementation of the new model, there was a 25% reduction in the
      proportion of encounters with patient handoffs, from 7.9% to 5.9%. A survey of
      physicians and charge nurses demonstrated improved perceptions of patient safety,
      ED flow, and job satisfaction. CONCLUSION: This new emergency physician staffing
      model with overlapping shifts decreased the proportion of patient handoffs. This
      innovative system can be implemented and scaled to suit EDs that have more than
      single-physician coverage.

PMID- 30287123
TI  - The association between subclinical inflammation and abnormal glucose and lipid
      metabolisms in normal-weight Korean individuals.
AB  - BACKGROUNDS AND AIMS: We aimed to reveal the association between subclinical
      inflammation and metabolic risk factors and to determine the difference in the
      association between normal-weight and obese Korean individuals. METHODS AND
      RESULTS: Data collected from the Korean National Health and Nutrition Examination
      Survey (KNHANES) 2015, conducted from January to December 2015, were analyzed.
      Overall, 4620 subjects were examined and divided into two subgroups: 2987 and
      1633 subjects in the normal-weight and obese groups, respectively. The prevalence
      of obesity in the study population was 34.5% (n = 1633). After multivariate
      adjustment, impaired fasting glucose (IFG) (odds ratio [OR] 1.22, 95% confidence
      interval [CI] 1.05-1.42, P = 0.010), high triglyceride (TG) levels (OR 1.29, 95%
      CI 1.13-1.47, P < 0.001), and low high-density lipoprotein-cholesterol (HDL-C)
      levels (OR 1.47, 95% CI 1.31-1.64, P < 0.001) were significantly associated with
      increased high-sensitivity C-reactive protein (hs-CRP) levels in the normal
      weight group but not in the obesity group. CONCLUSION: Subclinical inflammation
      was associated with IFG, high TG levels, and low HDL-C levels in normal-weight
      Korean individuals. Prospective and biochemical research is necessary to clarify
      the role of subclinical systemic inflammation in individuals with normal body
      weight and its impact on insulin resistance and abnormal lipid metabolism, which
      promote the incidence of metabolic syndrome and cardiovascular disease.

PMID- 30287124
TI  - A J-shaped relation of BMI and stroke: Systematic review and dose-response meta
      analysis of 4.43 million participants.
AB  - BACKGROUND AND AIM: Many studies have shown increased risk of stroke with greater
      adiposity as measured by body mass index (BMI), but questions remain about the
      shape of the dose-response relation. We conducted a systematic review and meta
      analysis of prospective studies to clarify the strength and shape of the dose
      response relation between BMI and risk of stroke. METHODS AND RESULTS: PubMed and
      Embase databases were searched for articles published up to May 11, 2018. Random
      effects generalized least-squares regression models were used to estimate study
      specific dose-response association, and restricted cubic splines were used to
      model the association. We included reports of 44 prospective cohort studies
      describing 102 466 incident cases among 4 432 475 participants. With a 5-unit
      increment in BMI, the summary relative risk for stroke incidence was 1.10 (95%
      confidence interval, 1.06 to 1.13; I2 = 88.0%). The dose-response relation was J
      shaped (Pnon-linearity <0.001). The risk was not increased at the low BMI range
      (<24 kg/m2), but was increased within the high BMI range (>25 kg/m2). CONCLUSION:
      Both overweight and obesity increase the risk of stroke with a J-shaped dose
      response relation, and the nadir of the curve was observed at BMI 23-24 kg/m2.

PMID- 30287126
TI  - Targeting enteric pathogens to improve childhood survival and growth.

PMID- 30287128
TI  - Comparison of ultrasonography and computed tomography in the determination of
      traumatic thoracic injuries.
AB  - OBJECTIVE: In this study, the accuracy of bedside thoracic ultrasonography (TUSG)
      performed by emergency physicians with patients in the supine position was
      compared with that of thoracic computed tomography (TCT) for the determination of
      thoracic injuries due to trauma. METHODS: Patients who suffered the multiple
      traumas, whose thoracic trauma was identified on physical examination or TCT
      imaging were included in the study. TUSG was performed following a physical
      examination by the emergency physician who managed the trauma patient.
      Subcutaneous emphysema, pneumothorax, pulmonary contusions (PCs), hemothorax,
      pericardial effusion and tamponade, sternal and clavicular fractures and rib
      fractures were identified by TUSG. TCT imaging was performed after the
      ultrasonography examination was completed. RESULTS: Eighty-one patients were
      included in the study. TCT scans showed subcutaneous emphysema in 16 (19.8%)
      patients, pneumothorax in 21 (25.9%), PCs in 27 (33.3%), hemothorax in 20
      (24.7%), sternum and clavicular fractures in 6 (7.4%) and rib fractures in 21
      (25.9%). The sensitivity and specificity of ultrasonography varied for detecting
      the following pathologies: subcutaneous emphysema (56% and 95%), pneumothorax
      (86% and 97%), hemothorax (45% and 98%), PCs (63% and 91%), sternal fractures
      (83% and 97%), clavicular fractures (83% and 100%) and rib fractures (67% and
      98%), respectively. CONCLUSION: In conclusion, ultrasound was found to be highly
      specific but only moderately sensitive for the identification of thoracic
      injuries.

PMID- 30287129
TI  - Assessment of proadrenomedullin as diagnostic or prognostic biomarker of acute
      appendicitis in children with acute abdominal pain.
AB  - BACKGROUND: Acute appendicitis (AA) is one of the most frequent surgical
      pathologies in pediatrics. OBJECTIVES: To investigate the utility of
      proadrenomedullin (pro-ADM) for the diagnosis of AA. METHODS: Prospective,
      analytical, observational, and multicenter study conducted in 6 pediatric
      emergency departments. Children up to 18 years of age with suspected AA were
      included. Clinical, epidemiological, and analytical data were collected. RESULTS:
      We studied 285 children with an average age of 9.5 years (95% confidence interval
      [CI], 9.1-9.9). AA was diagnosed in 103 children (36.1%), with complications in
      10 of them (9.7%). The mean concentration of pro-ADM (nmol/L) was higher in
      children with AA (0.51 nmol/L, SD 0.16) than in children with acute abdominal
      pain (AAP) of another etiology (0.44 nmol/L, SD 0.14; p < 0.001). This difference
      was greater in complicated cases compared with uncomplicated AA (0.64 nmol/L, SD
      0.17 and 0.50 nmol/L, SD 0.15, respectively; p = 0.005). The areas under the
      receiver-operating characteristic curves were 0.66 (95% CI, 0.59-0.72) for pro
      ADM, 0.70 (95% CI, 0.63-0.76) for C-reactive protein (CRP), 0.84 (95% CI, 0.79
      0.89) for neutrophils, and 0.84 (95% CI, 0.79-0.89) for total leukocytes. The
      most reliable combination to rule out AA was CRP <=1.25 mg/dL and pro-ADM <=0.35
      nmol/L with a sensitivity of 96% and a negative predictive value of 93%.
      CONCLUSION: Children with AA presented higher pro-ADM values than children with
      AAP of other etiologies, especially in cases of complicated AA. The combination
      of low values of pro-ADM and CRP can help to select children with low risk of AA.

PMID- 30287130
TI  - Round opacity as a presentation of pneumocystis jirovecii pneumonia in an HIV
      infected patient.
AB  - We present the case of a human immunodeficiency virus (HIV)-infected patient who
      arrived at our emergency department with fever, headache and exertional dyspnea.
      Throughout their stay, a chest x-ray was taken and a rounded opacity in his left
      lung was observed. CT images showed same abnormality and also ground glass
      opacities were seen. Symptoms and images strongly suggested a pulmonary infection
      due to pneumocystis jirovecii, however a presence of a round lesion should always
      lead to neoplasia being suspected. We empirically started treatment based on
      trimethoprim and sulfamethoxazole. Once available, flexible bronchoscopy and
      bronchoalveolar lavage was performed and stained preparations from his
      respiratory specimens confirmed the diagnosis of pulmonary pneumocystis
      infection. Finally, after 4 days of antibiotic therapy, an important clinical
      improvement was documented; a new chest x-ray was performed and the previous
      rounded opacity was absent. This finding strongly suggested a case of round
      pneumonia.

PMID- 30287125
TI  - Use of quantitative molecular diagnostic methods to investigate the effect of
      enteropathogen infections on linear growth in children in low-resource settings:
      longitudinal analysis of results from the MAL-ED cohort study.
AB  - BACKGROUND: Enteropathogen infections in early childhood not only cause diarrhoea
      but contribute to poor growth. We used molecular diagnostics to assess whether
      particular enteropathogens were associated with linear growth across seven low
      resource settings. METHODS: We used quantitative PCR to detect 29 enteropathogens
      in diarrhoeal and non-diarrhoeal stools collected from children in the first 2
      years of life obtained during the Etiology, Risk Factors, and Interactions of
      Enteric Infections and Malnutrition and the Consequences for Child Health and
      Development (MAL-ED) multisite cohort study. Length was measured monthly. We
      estimated associations between aetiology-specific diarrhoea and subclinical
      enteropathogen infection and quantity and attained length in 3 month intervals,
      at age 2 and 5 years, and used a longitudinal model to account for temporality
      and time-dependent confounding. FINDINGS: Among 1469 children who completed 2
      year follow-up, 35 622 stool samples were tested and yielded valid results.
      Diarrhoeal episodes attributed to bacteria and parasites, but not viruses, were
      associated with small decreases in length after 3 months and at age 2 years.
      Substantial decrements in length at 2 years were associated with subclinical, non
      diarrhoeal, infection with Shigella (length-for-age Z score [LAZ] reduction 
      0.14, 95% CI -0.27 to -0.01), enteroaggregative Escherichia coli (-0.21, -0.37 to
      -0.05), Campylobacter (-0.17, -0.32 to -0.01), and Giardia (-0.17, -0.30 to 
      0.05). Norovirus, Cryptosporidium, typical enteropathogenic E coli, and
      Enterocytozoon bieneusi were also associated with small decrements in LAZ.
      Shigella and E bieneusi were associated with the largest decreases in LAZ per log
      increase in quantity per g of stool (-0.13 LAZ, 95% CI -0.22 to -0.03 for
      Shigella; -0.14, -0.26 to -0.02 for E bieneusi). Based on these models,
      interventions that successfully decrease exposure to Shigella, enteroaggregative
      E coli, Campylobacter, and Giardia could increase mean length of children by 0.12
      0.37 LAZ (0.4-1.2 cm) at the MAL-ED sites. INTERPRETATION: Subclinical infection
      and quantity of pathogens, particularly Shigella, enteroaggregative E coli,
      Campylobacter, and Giardia, had a substantial negative association with linear
      growth, which was sustained during the first 2 years of life, and in some cases,
      to 5 years. Successfully reducing exposure to certain pathogens might reduce
      global stunting. FUNDING: Bill & Melinda Gates Foundation.

PMID- 30287131
TI  - Editorial overview: New concepts and experimental approaches to understand
      development, tissue regeneration, and human disease.

PMID- 30287132
TI  - Social Support and Its Effects on Adolescent Sexual Risk Taking: A Look at
      Vulnerable Populations in Baltimore and Johannesburg.
AB  - INTRODUCTION: We seek to understand whether and how much social support affects
      adolescent sexual risk-taking in disadvantaged urban environments. METHODS:
      Secondary analyses were conducted on data from the global Wellbeing of
      Adolescents (15-19years old) in Vulnerable Environments study. The outcomes of
      interest were sexual experience, age at sexual debut, number of lifetime sexual
      partners, and condom use at last sex. Social support scales measuring support at
      home, at school, and from peers were created, as well as a measure about who
      raised them. Logistic and linear regressions were used to examine associations
      between social support and sexual risk-taking after controlling for age,
      schooling, and family structure. RESULTS: Higher social support was associated
      with adolescents taking less sexual risk but it was context- and gender-specific.
      Boys raised by males had lower odds of having sex (adjusted odds ratios (aORs)
      from .15 (CI = .05-.42) to .19 (.04-.88)). Baltimore girls raised by grandmothers
      had lower odds of having sex (aOR .34 (.16-.71)). Female support at home was
      positively associated with girls in Baltimore (aOR .08 (CI = .04-.17)) and
      Johannesburg (aOR .17 (CI = .03-.87)) having fewer partners. Baltimore girls
      raised by fathers (aOR 3.78 (CI = 2.33-6.12)) and Johannesburg boys raised by non
      biological/step caregivers (aORs from 3.89 (CI = 1.12-13.44) to 8.85 (CI = 6.02
      12.99)) were more likely to use condoms. CONCLUSION: Young men without male
      support and young women lacking parental support are at particular risk of sexual
      risk-taking in disadvantaged communities. Parental support can be affected by
      other contextual factors. Violence in neighborhoods and at home should be
      considered.

PMID- 30287133
TI  - Reciprocal Associations Between Adolescent Girls' Chronic Interpersonal Stress
      and Nonsuicidal Self-Injury: A Multi-wave Prospective Investigation.
AB  - PURPOSE: Nonsuicidal self-injury (NSSI) is associated with increased risk of
      suicide attempts. Theories of NSSI assert interpersonal stress as a common risk
      factor for, and perhaps consequence of, NSSI. Prior research has not examined
      reciprocal associations between chronic interpersonal stress and NSSI. This study
      used a multiwave, prospective design to address this gap in a sample of
      adolescent girls, a group with elevated risk for both chronic interpersonal
      stress and NSSI. Pubertal development was examined as a moderator of the
      reciprocal associations. METHODS: Adolescent girls (N = 220; ages 12-16, M age =
      14.69 years) at heightened risk for NSSI completed a baseline assessment and
      follow-up assessments over 18 months, divided into two 9-month epochs (Time 1 and
      2). Pubertal development was assessed via self- and parent-report. Chronic
      interpersonal stress was assessed using a semistructured interview at the end of
      each time period. NSSI was measured using a semistructured clinical interview
      every 3 months within both time periods to enhance accurate reporting. RESULTS:
      Path models revealed that chronic romantic stress during Time 1, but not peer or
      parent-child stress, predicted NSSI during Time 2 among girls with more advanced
      pubertal development. Moreover, NSSI during Time 1 predicted higher levels of
      chronic romantic and parent-child stress during Time 2. CONCLUSIONS: Results
      revealed a reciprocal relationship between chronic romantic stress and engagement
      in NSSI. Further, this association may be best understood in the context of
      pubertal development.

PMID- 30287134
TI  - Refractory Hypotension Caused by Prazosin Overdose Combined With Acetaminophen
      and Naproxen Toxicity: A Case Report and Review of the Literature.
AB  - BACKGROUND: Pediatric exposure to prazosin is unusual because it is most commonly
      indicated for the treatment of hypertension. Prazosin's increase in popularity as
      a treatment for posttraumatic stress disorder makes it important for emergency
      physicians to be aware of how to manage potential toxic ingestion because of
      prazosin overdose. CASE REPORT: A 16-year-old, 76-kg female presented after
      ingesting 110 mg of prazosin, 209.3 g of acetaminophen, and 55 g of naproxen. She
      was admitted to the pediatric intensive care unit for rapidly deteriorating
      hypotension (lowest blood pressure 47/19 mm Hg) refractory to aggressive fluid
      resuscitation and infusions of epinephrine and norepinephrine each at 0.5
      mcg/kg/min. Stabilization of blood pressure was eventually achieved, and
      associated with use of a vasopressin infusion of 0.004 units/kg/min. WHY SHOULD
      AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Because of the increasing exposure of
      children to prazosin, clinicians should be aware of the pharmacology behind alpha
      1 antagonist overdose and consider treatment options, such as vasopressin, when
      hypotension is resistant to standard fluid and catecholamine therapy.

PMID- 30287127
TI  - Use of quantitative molecular diagnostic methods to assess the aetiology, burden,
      and clinical characteristics of diarrhoea in children in low-resource settings: a
      reanalysis of the MAL-ED cohort study.
AB  - BACKGROUND: Optimum management of childhood diarrhoea in low-resource settings
      has been hampered by insufficient data on aetiology, burden, and associated
      clinical characteristics. We used quantitative diagnostic methods to reassess and
      refine estimates of diarrhoea aetiology from the Etiology, Risk Factors, and
      Interactions of Enteric Infections and Malnutrition and the Consequences for
      Child Health and Development (MAL-ED) cohort study. METHODS: We re-analysed stool
      specimens from the multisite MAL-ED cohort study of children aged 0-2 years done
      at eight locations (Dhaka, Bangladesh; Vellore, India; Bhaktapur, Nepal; Naushero
      Feroze, Pakistan; Venda, South Africa; Haydom, Tanzania; Fortaleza, Brazil; and
      Loreto, Peru), which included active surveillance for diarrhoea and routine non
      diarrhoeal stool collection. We used quantitative PCR to test for 29
      enteropathogens, calculated population-level pathogen-specific attributable
      burdens, derived stringent quantitative cutoffs to identify aetiology for
      individual episodes, and created aetiology prediction scores using clinical
      characteristics. FINDINGS: We analysed 6625 diarrhoeal and 30 968 non-diarrhoeal
      surveillance stools from 1715 children. Overall, 64.9% of diarrhoea episodes (95%
      CI 62.6-71.2) could be attributed to an aetiology by quantitative PCR compared
      with 32.8% (30.8-38.7) using the original study microbiology. Viral diarrhoea
      (36.4% of overall incidence, 95% CI 33.6-39.5) was more common than bacterial
      (25.0%, 23.4-28.4) and parasitic diarrhoea (3.5%, 3.0-5.2). Ten pathogens
      accounted for 95.7% of attributable diarrhoea: Shigella (26.1 attributable
      episodes per 100 child-years, 95% CI 23.8-29.9), sapovirus (22.8, 18.9-27.5),
      rotavirus (20.7, 18.8-23.0), adenovirus 40/41 (19.0, 16.8-23.0), enterotoxigenic
      Escherichia coli (18.8, 16.5-23.8), norovirus (15.4, 13.5-20.1), astrovirus
      (15.0, 12.0-19.5), Campylobacter jejuni or C coli (12.1, 8.5-17.2),
      Cryptosporidium (5.8, 4.3-8.3), and typical enteropathogenic E coli (5.4, 2.8
      9.3). 86.2% of the attributable incidence for Shigella was non-dysenteric. A
      prediction score for shigellosis was more accurate (sensitivity 50.4% [95% CI
      46.7-54.1], specificity 84.0% [83.0-84.9]) than current guidelines, which
      recommend treatment only of bloody diarrhoea to cover Shigella (sensitivity 14.5%
      [95% CI 12.1-17.3], specificity 96.5% [96.0-97.0]). INTERPRETATION: Quantitative
      molecular diagnostics improved estimates of pathogen-specific burdens of
      childhood diarrhoea in the community setting. Viral causes predominated,
      including a substantial burden of sapovirus; however, Shigella had the highest
      overall burden with a high incidence in the second year of life. These data could
      improve the management of diarrhoea in these low-resource settings. FUNDING: Bill
      & Melinda Gates Foundation.

PMID- 30287135
TI  - Not Just Another "Found Down": Concomitant Upper Arm and Gluteal Compartment
      Syndrome.
AB  - BACKGROUND: Compartment syndrome is often considered in patients with long-bone
      fractures and soft-tissue injuries, but is not as commonly associated with a
      period of unconsciousness. CASE REPORT: A 65-year-old man was brought to our
      emergency department (ED) because he had lost consciousness for an unknown amount
      of time after snorting heroin. He had severe pain in his upper right arm.
      Physical examination revealed right arm edema, paresthesia, tenderness, and
      firmness to palpation. During the ED assessment, the patient began to experience
      pain in his right hip to a degree exceeding examination findings. We considered
      compartment syndrome affecting his upper arm as well as his gluteal muscles. The
      patient was taken to the operating room for fasciotomy. The triceps muscle was
      found to be bulging out of the compartment, demonstrating advanced compartment
      syndrome. A posterior approach to the hip allowed the gluteal sling and the
      fascia to be released, eliminating tension on the gluteus medius/minimus and
      gluteus maximus compartments. With physical therapy, the patient regained full
      flexion and extension in his arm at the elbow, partial extension of his wrist,
      and range of motion and strength in his hip. WHY SHOULD AN EMERGENCY PHYSICIAN BE
      AWARE OF THIS?: If not recognized, compartment syndrome can jeopardize limb and
      life. It should be considered in patients experiencing inordinate pain,
      especially if they were found unconscious at the incident scene. Pressure-induced
      ischemia can impair muscle function within hours. If it is not relieved with
      fasciotomy, the patient can sustain irreversible functional loss.

PMID- 30287136
TI  - Comparison of the Accuracy of Emergency Department-Performed Point-of-Care
      Ultrasound in the Diagnosis of Lower-Extremity Deep Vein Thrombosis.

PMID- 30287137
TI  - Sleep disorders: Serious threats among kidney transplant recipients.
AB  - In patients with chronic kidney disease (CKD) and kidney transplant recipients
      who continue to have some degree of CKD, the prevalence of sleep-related
      disorders is very high. Common sleep disorders in both groups include insomnia,
      sleep-disordered breathing (SDB), restless legs syndrome (RLS), excessive daytime
      sleepiness (EDS), and others. Depending on the kidney graft function, some
      patients see sleep disorders resolve after kidney transplantation, while others
      continue to have persistent sleep disorders or develop new ones. Kidney
      transplant recipients (KTRs) are unique patients due to the presence of a single
      kidney, the use of immunosuppressive medications, and other comorbidities
      including obesity, a high risk of cardiovascular disease, malignancy, and the
      anxiety of losing their allograft. All of these factors contribute to the risk
      for sleep disorders. CKD and sleep disorders have a bidirectional relationship;
      that is, CKD may increase the risk of sleep disorders and sleep disorders may
      increase the risk of CKD. Obstructive sleep apnea (OSA) is the most common form
      of SDB and is known to alter renal hemodynamics. OSA leads to hypoxemia and
      sleeps fragmentation, which activates the sympathetic nervous system. This
      activates the renin-angiotensin-aldosterone system and ultimately alters
      cardiovascular hemodynamics. Sleep disorders may have deleterious effects on the
      kidney allograft and proper screening and management are important for both graft
      and patient survival.

PMID- 30287138
TI  - Objective assessment of early urinary continence by analysis and visualisation of
      intraoperative variables of radical robotic prostatectomies with a video editor.
AB  - INTRODUCTION: UI after RP is a factor that has a major impact on patients'
      quality of life and the associated healthcare costs. The definition of UI is very
      variable in the literature. Similarly, a great many predictors have been studied
      that affect recovery of continence after surgery, the most important of which are
      intraoperative. MATERIAL AND METHODS: a retrospective and observational study
      performed between September 2008 and March 2015. We studied intraoperative
      factors through visualisation using a video editor of 148 patients who underwent
      robot-assisted radical prostatectomy, together with other perioperative factors
      associated with continence, and described in the literature. We assessed
      continence through ICQ questionnaires, urinary loss calculated by pad count, and
      clinical interview in the first, third, sixth month and at one year after
      surgery. We defined continence as not having to use a pad or using a pad for
      protection socially, or an ICQ <= 7. We used binary and lineal logistic
      regression analysis to study the relationship between the intraoperative and
      perioperative variables on urinary continence measured at the first, third, sixth
      month and one year after the operation, and on continence stability. RESULTS: In
      our study, 72.9% of the patients were continent at one year after surgery with a
      mean continence stabilisation time at 4.3 months. In our lineal logistic
      regression analyses we found no significant relationship with the continence
      variable analysed during the first year. In the lineal logistic regression
      analysis we found that tension-free sutures had a direct positive effect (P<=.05)
      on the stability time of continence, as well as the urinary losses measured in
      the first month after surgery. CONCLUSION: In conclusion, we found in our study
      that the tension-free sutures were able to help towards early stability of
      continence. We found no other intraoperative predictors that influenced urinary
      continence. The urinary losses measured in the first month related to early
      recovery of continence.

PMID- 30287139
TI  - Sarcomatoid urothelial bladder carcinoma in adults: Histology, symptomatology,
      treatments and survival.
AB  - OBJECTIVE: Sarcomatoid urothelial bladder carcinoma comprises 3% of the tumours
      of the bladder and is considered one of the most aggressive tumours of the
      urinary tract. Our aim is to analyse the characteristics of sarcomatoid
      urothelial bladder carcinoma in adults, its treatments and survival. METHOD: A
      retrospective study performed between 2000 and 2017 of all the patients with a
      sarcomatoid urothelial bladder carcinoma in a single centre. We studied the
      anatomopathological characteristics, symptoms at time of diagnosis, treatment
      given and survival according to the treatment given. RESULTS: Sixteen patients
      were diagnosed with sarcomatoid carcinoma, 11 with no heterologous component, one
      with rhabdomyosarcomatous components, 2 with chondrosarcomatous components and 2
      with osteosarcomatous components. The mean age was 74 years (+/-20) and 88% were
      smokers. The primary symptom was haematuria, and the least well-tolerated was
      dysuria together with hypogastric pain. Ninety-four percent of the patients had
      muscle layer infiltration and 18% had metastases at the time of diagnosis. Thirty
      seven percent of the patients were treated by radical cystectomy, thirteen
      percent by radical cystectomy plus adjuvant chemotherapy, and 50% were treated by
      palliative transurethral resection to control their symptoms. A survival curve
      was made with the different treatments given, which showed a mean global survival
      of 7 months and no statistically significant differences in terms of survival
      according to the treatment given. CONCLUSIONS: Sarcomatoid urothelial carcinoma
      is an aggressive disease, of rapid and torpid onset which occurs in patients of
      advanced age and smokers. There are no established treatment guidelines, and it
      appears that no treatment influences increased survival. Cystectomy should be
      evaluated as a treatment alternative for patients whose symptoms are difficult to
      control. The various heterologous components do not appear to influence the
      progression of the disease or patient survival.

PMID- 30287141
TI  - Dynamics of ionic liquids in poly(vinyl alcohol) porous scaffold. Low field NMR
      study.
AB  - In this study molecular dynamics of ionic liquids in poly(vinyl alcohol)
      scaffolds were investigated. The binary poly(vinyl alcohol) - ionic liquid (PVA
      IL) compound was prepared from initial solutions of water, ionic liquid (IL) and
      poly(vinyl alcohol) (PVA) at different concentrations. Subsequently water was
      evaporated under open conditions, leaving the scaffold/IL system of interest. Low
      field nuclear magnetic resonance (NMR) relaxation and diffusion measurements, as
      well as 2D T1-T2 correlated NMR experiments were performed to determine specific
      local and translational dynamics properties at different time scales. Data
      suggest that during water evaporation, partial demixing of IL from the polymeric
      matrix leaves the remaining solvent confined in the porous structure formed by
      the PVA polymer. The results show that the translational diffusion, as well as
      the local rotational molecular dynamics is comparable to the bulk liquid state.
      Moreover, in partial saturation conditions, diffusion shows enhancements relative
      to the bulk.

PMID- 30287142
TI  - CCL20, a direct-acting pro-angiogenic chemokine induced by hepatitis C virus
      (HCV): Potential role in HCV-related liver cancer.
AB  - The CCL20/CCR6 chemokine/receptor axis has previously been shown to contribute to
      the initiation and progression of hepatocellular carcinoma (HCC) through the
      recruitment of CCR6-positive leukocytes to the tumor microenvironment. In
      particular, high serum levels of CCL20 are reported in patients with HCC induced
      by the hepatitis C virus (HCV). A potential non-immune role for the CCL20/CCR6
      axis in HCC development has not yet been investigated. Microarray analysis
      (Benkheil et al., paper submitted for publication), revealed that CCL20 is highly
      upregulated in hepatoma cells infected with HCV compared with non-infected
      hepatoma cells. To determine the role of the CCL20/CCR6 axis in HCV-related HCC,
      we first explored which cell populations express CCR6 in human liver tissue with
      chronic disease or HCC. Immunohistochemical (IHC) analysis revealed that CCR6 is
      present on endothelial cells (ECs) of portal blood vessels in livers with chronic
      HCV infection and in HCV- and alcoholic-HCC tissue. In addition, we found CCR6 to
      be expressed on primary macrovascular (HUVECs) and microvascular ECs (HMVEC-ds)
      where it co-expressed with the endothelial marker CD31. In vitro angiogenesis
      experiments revealed that CCL20 is a direct pro-angiogenic molecule that induces
      EC invasion, sprouting and migration through CCR6. Moreover, using the
      angiogenesis matrigel plug assay in immunodeficient NMRI-nu mice, we clearly
      showed that CCL20 induces blood vessel formation, by attracting CCR6-positive
      ECs. Finally, we demonstrated that HCV-induced CCL20 protein expression and
      secretion in hepatoma cells could be abolished by antiviral treatment, indicating
      that CCL20 expression is dependent on HCV replication. In contrast to HCV, HBV
      infection resulted in a decreased expression of CCL20, implying a virus-specific
      effect. Taken together, we identified HCV-induced CCL20 as a direct pro
      angiogenic factor that acts on endothelial CCR6. These results suggest that the
      CCL20/CCR6 axis contributes to hepatic angiogenesis, promoting the hypervascular
      state of HCV-HCC.

PMID- 30287143
TI  - LL-37 inhibits LPS-induced inflammation and stimulates the osteogenic
      differentiation of BMSCs via P2X7 receptor and MAPK signaling pathway.
AB  - Oral diseases, such as periapical periodontitis and periodontitis, are
      characterized by inflammation-induced bone loss. LL-37, a human antimicrobial
      peptide (AMP), has multiple biological functions and the potential to promote
      osteogenesis. Therefore, this study aimed to investigate the regulatory effects
      of LL-37 within normal and inflammatory microenvironments. The roles of P2X7
      receptor (P2X7R) and mitogen-activated protein kinase (MAPK) signaling pathway
      were also demonstrated. The results showed that LL-37 promoted bone marrow
      stromal cell (BMSC) proliferation, migration and osteogenic differentiation. LL
      37 inhibited the expression of the inflammatory cytokines interleukin-1beta (IL
      1beta), tumor necrosis factor-alpha (TNF-alpha) and receptor activator of nuclear
      factor kappa-B ligand (RANKL) at both protein and gene levels, and attenuated the
      lipopolysaccharide (LPS)-induced inhibition of osteogenesis. Immunofluorescence
      (IF) confirmed P2X7R expression in BMSCs. BBG, a P2X7R antagonist, significantly
      attenuated LL-37-promoted osteogenesis. The phosphorylation of extracellular
      signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK)
      increased after LL-37 stimulation, which did not affect p38 phosphorylation. The
      effects of LL-37 on osteogenesis-related gene expression were markedly attenuated
      by selective inhibitors of ERK1/2 and JNK. Furthermore, a mouse model of LPS
      stimulated calvarial osteolysis was established, and results showed that LL-37
      markedly inhibited osteoclastic bone resorption. In conclusion, we speculate that
      LL-37 inhibits inflammation and promotes BMSC osteogenesis via P2X7R and MAPK
      signaling pathway.

PMID- 30287144
TI  - Efficacy of heart failure reversal treatment followed by 90 days follow up in
      chronic heart failure patients with low ejection fraction.
AB  - BACKGROUND: Heart failure reversal therapy (HFRT) is designed to enhance
      cardiorespiratory fitness of chronic heart failure (CHF) patients. OBJECTIVES:
      The present study was designed to evaluate efficacy of HFRT that uses herbal
      procedure (panchakarma) and allied therapies, in CHF patients with low ejection
      fraction. METHODS: This efficacy study was conducted in CHF patients (aged: 25-65
      years, ejection fraction (EF) 10-30%) wherein HFRT (60-75 min) consisting of
      snehana (external oleation), swedana (passive heat therapy), hrudaydhara
      (concoction dripping treatment) and basti (enema) was administered twice daily
      for 7 days. During this therapy and next 30 days, patients followed the study
      dinarcharya and were prescribed ARJ kadha in addition to their conventional
      treatment. The primary endpoint of this study was evaluation of maximum aerobic
      capacity uptake (MAC) as assessed by 6 min walk distance (6MWD) using Cahalins
      equation from baseline, at the end of 7 day treatment, follow-up after 30 days
      and 90 days. EF was assessed by 2D Echo at baseline and after 30 days of follow
      up. RESULTS: Fifty-two CHF patients with 10-30% EF (mean [SD] age: 58.8 [10.8],
      85% men) were enrolled in the study. There was a 100% compliance to study
      therapy. A significant improvement was observed in MAC levels (7.11%, p = 0.029),
      at the end of 7 day therapy as compared to baseline. This improvement was
      maintained at two follow-up visits. Moreover ejection fraction was observed to be
      increased by 6.38%, p = 0.012 as compared to baseline at day 7 of the therapy.
      CONCLUSION: This 90 day follow up study highlights the benefit of HFRT, as a part
      of maintenance treatment for CHF patients with reduced ejection fraction.

PMID- 30287140
TI  - Biochemical Aspects of PD-L1 Regulation in Cancer Immunotherapy.
AB  - PD-L1, frequently expressed in human cancers, engages with PD-1 on immune cells
      and contributes to cancer immune evasion. As such, antibodies blocking the PD
      1/PD-L1 interaction reactivate cytotoxic T cells to eradicate cancer cells.
      However, a majority of cancer patients fail to respond to PD-1/PD-L1 blockade
      with unclear underlying mechanism(s). Recent studies revealed that PD-L1
      expression levels on tumor cells might affect the clinical response to anti-PD
      1/PD-L1 therapies. Hence, understanding molecular mechanisms for controlling PD
      L1 expression will be important to improve the clinical response rate and
      efficacy of PD-1/PD-L1 blockade. In this review, we primarily focus on
      summarizing PD-L1 regulation and its potential roles in regulating antitumor
      immune response, with purpose to optimize anti-PD-1/PD-L1 therapies, benefiting a
      wider cancer patient population.

PMID- 30287145
TI  - Robustness of Textural Features to Predict Stone Fragility Across Computed
      Tomography Acquisition and Reconstruction Parameters.
AB  - RATIONALE AND OBJECTIVES: Previous studies have demonstrated that quantitative
      relationships exist between stone fragility at lithotripsy and morphological
      features extracted from computed tomography (CT) scans. The goal of this study
      was to determine if variations in scanner model, patient size, radiation dose, or
      reconstruction parameters impact the accuracy of the prediction of renal stone
      fragility in an in vitro model. MATERIALS AND METHODS: Sixty-seven kidney stones
      were scanned using routine single and dual energy stone protocols, mimicking
      average, and large patient habitus. Low dose scans were also performed. Each scan
      was reconstructed with routine protocol parameters, and with thinner (0.6 mm) or
      thicker (3mm) images, two different reconstruction kernels, and iterative
      reconstruction at two strengths. Fragilityof each stone was measured in a
      controlled ex vivo experiment. A single predictive model was developed from a
      reference CT protocol configuration and applied to data from each CT acquisition
      and reconstruction parameter tested to obtain estimated stone comminution times.
      RESULTS: None of the investigated protocols showed a significant variation in the
      accuracy of stone fragility classification, except for the ones with the most
      aggressive iterative reconstruction and/or with thicker images. In these
      protocols, a number of stone fragility assessments changed from fragile to hard
      (or vice versa), compared to their ground truth measurement. CONCLUSION:
      Prediction accuracy of stone fragility models developed from CT data is robust to
      expected variations in CT stone protocols used for quantification tasks. This
      finding facilitates their future adoption to different clinical practices.

PMID- 30287146
TI  - The reliability, validity, and methodologic quality of measurements used to
      quantify posterior shoulder tightness: a systematic review of the literature with
      meta-analysis.
AB  - HYPOTHESIS AND BACKGROUND: Posterior shoulder tightness (PST) has been linked to
      numerous shoulder pathologies in both the general and athletic populations.
      Several methods for documenting PST have been described in the literature, which
      may lend to variability in clinical practice and research. The purpose of this
      study was to perform a systematic review with meta-analysis to investigate the
      reliability, validity, and methodologic quality of methods used to quantify PST.
      METHODS: Relevant studies were assessed for inclusion, and selected studies were
      identified from the PubMed, Embase, Cochrane, and CINAHL (Cumulative Index to
      Nursing and Allied Health Literature) databases. Data were extracted from the
      selected studies and underwent methodologic quality assessment and meta-analysis.
      RESULTS: The search resulted in 1006 studies identified, with 18 ultimately
      retained. Intrarater reliability was reported in 12 studies with a summary
      intraclass correlation coefficient of 0.93 (95% confidence interval, 0.90-0.95),
      whereas inter-rater reliability was reported in 6 studies with a summary
      intraclass correlation coefficient of 0.89 (95% confidence interval, 0.80-0.94).
      Validity was reported in 10 studies, all using internal rotation as the
      convergent standard, and was found to be significant in all but 1 study.
      CONCLUSION: Current methods used to quantify PST have good reliability but are
      primarily limited to measures of horizontal adduction of the glenohumeral joint
      with scapular stabilization. Limitations in using a single measurement technique
      exist particularly as there may be multiple contributing factors to PST. A more
      comprehensive approach for quantifying PST is necessary, and suggested components
      include a cluster of techniques composed of horizontal adduction, internal
      rotation, and total glenohumeral joint range of motion.

PMID- 30287147
TI  - Social resource assessment: Application of a novel communication tool during
      hospital discharge.
AB  - OBJECTIVE: To evaluate an interactive tool designed to help patients communicate
      their social resources supportive of home recovery to health care providers.
      METHODS: Seventy medical and surgical inpatients completed the D-CEGRM social
      resource interview, demographic queries, and discharge readiness surveys (RHDS)
      at discharge. Two weeks later, patients completed post-discharge coping
      difficulty surveys (PDCDS). Nurses unassociated with patients' clinical care
      reviewed structured clinical notes created from the D-CEGRM and categorized
      patients as likely to have "inadequate" or "adequate" supportive resources for
      home self-management. Nurse decision making was tracked using an adjudication
      process, and post-hoc comparisons in patient characteristics, RHDS, and PDCDS
      were conducted. RESULTS: Nurses categorized 36 patients (51%) as having
      inadequate resources. Number and accessibility of supports, presence of negative
      relationships, and previous struggles meeting health-related needs were important
      decision-making factors. Post-hoc comparisons revealed significant differences in
      demographic risk factors and discharge readiness ratings for those with
      inadequate vs. adequate resources. CONCLUSION: The D-CEGRM may be an efficient
      tool for patients to communicate access to social resources, and an effective
      facilitator of transitional care planning. PRACTICE IMPLICATIONS: The D-CEGRM may
      provide a useful assessment of patients' home context and guide for transitional
      care planning.

PMID- 30287149
TI  - Reply to "The choice of antiviral therapy for hepatitis C recurrence after liver
      transplantation in the real world".

PMID- 30287148
TI  - The added value of therapist communication on the effect of physical therapy
      treatment in older adults; a systematic review and meta-analysis.
AB  - OBJECTIVE: Lower physical activity levels in older adults are associated with
      increased co-morbidities and disability. Physical therapists have a critical role
      in facilitating increases in physical activity. The communication they use may
      impact their effectiveness. This study investigates the additional value of
      therapist's communication during physical therapy on older adults' physical
      activity levels. METHODS: Systematic review and meta-analysis. Clinical trials
      were identified in PubMed, CINAHL, Embase, PsycINFO, PEDro, Cochrane, up to July
      2016. Communication was classified with the Behavior Change Taxonomy(BCT). Effect
      sizes were pooled using Cochrane's Review-Manager. Strength of the evidence was
      analyzed using GRADE's criteria. RESULTS: Twelve studies were identified.
      Overall, communication techniques revealed an immediate and long-term
      effect(ES:0.19;0.24) on self-reported physical activity measures but not on
      performance-based, with moderate to high strength of evidence. Divided in BCT
      categories, only 'Generalisation of target behavior', defined as communication
      aimed to help patients generalise an exercise from one situation to another at
      home, had a positive effect on self-reported activity(ES:0.34), with low strength
      of evidence. CONCLUSION: Adding a communication technique to physical therapy is
      effective on self-reported physical activity measures but not on performance
      based measures. PRACTICE IMPLICATIONS: Add communication to exercise when
      treatment aims at perceived, but not performed, physical activity.

PMID- 30287150
TI  - Oxytocin and excitation/inhibition balance in social recognition.
AB  - Social recognition is the sensitive domains of complex behavior critical for
      identification, interpretation and storage of socially meaningful information.
      Social recognition develops throughout childhood and adolescent, and is affected
      in a wide variety of psychiatric disorders. Recently, new data appeared on the
      molecular mechanisms of these processes, particularly, the excitatory-inhibitory
      (E/I) ratio which is modified during development, and then E/I balance is
      established in the adult brain. While E/I imbalance has been proposed as a
      mechanism for schizophrenia, it also seems to be the common mechanism in autism
      spectrum disorder (ASD). In addition, there is a strong suggestion that the
      oxytocinergic system is related to GABA-mediated E/I control in the context of
      brain socialization. In this review, we attempt to summarize the underpinning
      molecular mechanisms of E/I balance and its imbalance, and related biomarkers in
      the brain in healthiness and pathology. In addition, because there are increasing
      interest on oxytocin in the social neuroscience field, we will pay intensive
      attention to the role of oxytocin in maintaining E/I balance from the viewpoint
      of its effects on improving social impairment in psychiatric diseases, especially
      in ASD.

PMID- 30287151
TI  - Vitamin D protects against diabetic nephropathy: Evidence-based effectiveness and
      mechanism.
AB  - Vitamin D has been suggested to harbor multiple biological activities, among them
      the potential of vitamin D in the protection of diabetic nephropathy (DN) has
      attracted special attention. Both animal studies and clinical trials have
      documented an inverse correlation between low vitamin D levels and DN risk, and
      supplementation with vitamin D or its active derivatives has been demonstrated to
      improve endothelial cell injury, reduce proteinuria, attenuate renal fibrosis,
      and resultantly retard DN progression. Vitamin D exerts its pharmacological
      effects primarily via vitamin D receptor, whose activation inhibits the renin
      angiotensin system, a key culprit for DN under hyperglycemia. The anti-DN benefit
      of vitamin D can be enhanced when administrated in combination with angiotensin
      converting enzyme inhibitors or angiotensin II receptor blockers. Mechanistic
      studies reveal that pathways relevant to inflammation participate in the
      pathogenesis of DN, however, consumption of vitamin D-related products negatively
      regulates inflammatory response at multiple levels, indicated by inhibiting
      macrophage infiltration, nuclear factor-kappa B (NF-kappaB) activation, and
      production of such inflammatory mediators as transforming growth factor-beta(TGF
      beta), monocyte chemoattractant protein 1(MCP-1), and regulated upon activation
      normal T cell expressed and secreted protein(RANTES). The robust anti
      inflammatory property of vitamin D-related products allows them with a promising
      renoprotective therapeutic option for DN. This review summarizes new advances in
      our understanding of vitamin D-related products in the DN management.

PMID- 30287152
TI  - (-)-alpha-bisabolol prevents neuronal damage and memory deficits through
      reduction of proinflammatory markers induced by permanent focal cerebral ischemia
      in mice.
AB  - The pathophysiology of ischemic stroke involves multiple events such as
      inflammation and oxidative stress which will lead to neuronal death and cognitive
      deficits. The (-)-alpha-bisabolol is a monocyclic sesquiterpene alcohol found in
      various plants and mainly in Matricaria chamomilla, which exerts antioxidant,
      anti-inflammatory, and anti-apoptotic activities. The aim of this work was to
      investigate the neuroprotective effects of (-)-alpha-bisabolol in mice underwent
      permanent occlusion of the middle cerebral artery (pMCAO). Animals were treated
      with (-)-alpha-bisabolol (50, 100 and 200 mg/kg/day, orally) or vehicle (3% tween
      80) one day before and 1 h after pMCAO and the treatment continued once daily for
      the following five days. The treatment with (-)-alpha-bisabolol (100 and 200
      mg/kg) significantly reduced the infarcted area and neurological deficits caused
      by pMCAO. (-)-alpha-bisabolol at the 200 mg/kg dose increased cell viability and
      decreased neuronal degeneration, as evaluated by cresyl violet and Fluoro-Jade C
      stainings, respectively. (-)-alpha-bisabolol also increased the locomotor
      activity which was reduced by cerebral ischemia and improved pMCAO-induced
      working, spatial, object recognition, and aversive memories deficits. (-)-alpha
      bisabolol (200 mg/kg) significantly prevented the increase of myeloperoxidase
      (MPO) activity, TNF-alpha immunoreactivity in the temporal cortex, and the
      increase of iNOS both in the temporal cortex and in the striatum. (-)-alpha
      bisabolol treatment also prevented astrogliosis in these areas. These data showed
      that (-)-alpha-bisabolol provides neuroprotective action probably due to its anti
      inflammatory activity, although other mechanisms cannot be discarded.

PMID- 30287153
TI  - Escin induces apoptosis in human bladder cancer cells: An in vitro and in vivo
      study.
AB  - Escin (beta-escin) is used as traditional folk medicine. The anti-tumour effects
      of escin have been demonstrated in vitro in certain cell lines, but its effect on
      bladder cancer has not been well investigated. In this study, the apoptotic
      activity of escin dissolved in dimethyl sulfoxide (DMSO) in bladder cancer cells
      and normal peripheral blood mononuclear cells (PBMC) and SV-HUC1 cells (controls)
      was determined. Cell cytotoxicity was assessed using the MTT assay. Cell cycle,
      Reactive oxygen species (ROS) generation, annexin V-FITC staining (for detecting
      early apoptosis), and changes in mitochondrial membrane potential were evaluated
      using flow cytometry. Expression of apoptosis-related proteins such as Fas (CD95)
      death receptor/FADD (Fas-associated protein with death domain) and BCL2 family of
      proteins was assessed using immunoblotting. Escin dose-dependently inhibited the
      growth of human bladder cancer cells, and showed IC50 of ~40 MUM. The cell
      population in the sub-G1 phase, annexin-V staining, Fas expression, ratio of
      BAX/BCL2, cleavage of activated caspase-3/-8/-9, increase in poly (ADP-ribose)
      polymerase (PARP) levels, and suppression of nuclear factor kappa B (NF-kappaB)
      were observed after 24 h of escin treatment. Escin decreased mitochondrial
      membrane potential and increased cytochrome C release via generation of reactive
      oxygen species, which led to apoptosis of bladder cancer cells. Furthermore,
      escin effectively inhibited bladder tumour growth in a xenograft mouse model.
      Together, these results demonstrate that escin induces apoptosis in human bladder
      cancer cells through the Fas death receptor and mitochondrial pathways and
      inhibits bladder tumour growth. Escin is a potential chemotherapeutic agent for
      bladder cancer.

PMID- 30287154
TI  - Mechanisms underlying select chemotherapeutic-agent-induced neuroinflammation and
      subsequent neurodegeneration.
AB  - This review demonstrates the importance of uncovering the mechanisms that
      underlie chemotherapy-induced neuroinflammation. It builds upon the well
      established connection between chemotherapeutic-agents and neurotoxicity along
      with widespread peripheral toxicities. This article summarises the major studies
      which have linked chemotherapy-induced neurodegeneration with direct evidence of
      neuroinflammation. Cancer and chemotherapy-related adverse effects impact a large
      proportion of the population. A better understanding of the link between
      chemotherapy, neurotoxicity and specifically the mechanisms of neuroinflammation,
      will allow the development of strategies to improve the management of side
      effects, and overall to reduce the burden on cancer patients receiving
      chemotherapy. This review has developed a summary schematic of the relationship
      between different chemotherapeutic agents and inflammatory markers within the
      central nervous system and links this correlation with some major ailments
      associated with chemotherapy use.

PMID- 30287155
TI  - N-Benzyl-N-methyl-dodecan-1-amine, a novel compound from garlic, exerts anti
      cancer effects on human A549 lung cancer cells overexpressing cancer upregulated
      gene (CUG)2.
AB  - Dietary garlic has been suggested to possess anticancer properties, and several
      attempts have been made to isolate the anticancer compounds. In this study, we
      efficiently synthesized N-benzyl-N-methyl-dodecan-1-amine (BMDA) by the reductive
      amination method. We evaluated the potential anticancer activities of BMDA
      against A549 lung cancer cells with cancer stem cell-like phenotypes due to the
      overexpression of cancer upregulated gene (CUG)2. N-Benzyl-N-methyl-dodecan-1
      amine treatment sensitized A549 cells overexpressing CUG2 (A549-CUG2) to
      apoptosis and autophagy compared with those of the control cells. The treatment
      with BMDA also reduced tumor development in xenografted nude mice. Furthermore,
      BMDA inhibited cell migration, invasion, and sphere formation in A549-CUG2 cells,
      in which TGF-beta signaling is involved. Further analysis showed that BMDA
      hindered TGF-beta promoter activity, protein synthesis, and phosphorylation of
      Smad2, thus decreasing the expression of TGF-beta-targeted proteins, including
      Snail and Twist. N-Benzyl-N-methyl-dodecan-1-amine also decreased Twist
      expression in vivo. In addition, BMDA inhibited Akt-ERK activities, beta-catenin
      expression, and its transcriptional activity. These results suggest that BMDA can
      be a promising anticancer agent against cancer cells overexpressing CUG2.

PMID- 30287156
TI  - Epitope clustering analysis for vaccine-induced human antibodies in relationship
      to a panel of murine monoclonal antibodies against HPV16 viral capsid.
AB  - Human papillomavirus (HPV) type 16 is the most common type implicated as the
      etiological agent that causes cervical cancer. The marketed prophylactic vaccines
      against HPV infection are composed of virus-like particles (VLPs) assembled from
      the recombinant major capsid protein L1. Elicitation of functional and
      neutralizing antibodies by vaccination is the mode of action by which the
      vaccines prevent the viral infection. In this study, a panel of murine mAbs
      against HPV16 L1 were generated and comprehensively characterized with respect to
      their mapping to the epitope spectrum on the viral capsid. These mAbs were
      categorized into five epitope bins by two different methods based on the pairwise
      cross-inhibition and competition with human polyclonal antibodies. In addition, a
      preliminary demonstration of the spatial relationship of the epitopes recognized
      by these mAbs was performed using a cross-blocking assay with a well
      characterized human mAb, 26D1. Interestingly, two mAbs recognizing different
      epitopes were found to act synergistically in the pseudovirion-based
      neutralization assay (PBNA). To facilitate cross-lab and cross-study comparison,
      the international standard (IS) serum 05/134 was used to calibrate the mAbs as
      well as the human serum samples from the HPV16/18 vaccine recipients. The
      neutralizing mAbs, particularly those that recognizing immunodominant epitopes,
      would be useful in developing epitope-specific assays for monitoring the vaccine
      production process and for serological assessment.

PMID- 30287157
TI  - Assessing the effectiveness of high-dose influenza vaccine in preventing
      hospitalization among seniors, and observations on the limitations of
      effectiveness study design.
AB  - BACKGROUND: The availability of high-dose (HD) influenza vaccine for seniors
      should decrease influenza-related hospitalization. Studies to date show a range
      of mostly moderate increased HD vaccine effectiveness (VE). While a 'healthy
      vaccinee' phenomenon can inflate VE, for influenza and particularly an HD vaccine
      targeted at frailer adults, an 'at-risk vaccinee' bias may deflate VE estimates.
      We assessed senior HD vaccine effectiveness against influenza-related
      hospitalization by linking immunization registry records to hospitalizations. We
      also examined whether adding strata typically ignored in case-control matching
      schemas, such as residence areas, exact age, and provider biases, would increase
      VE. METHODS: For the 2016-17 influenza season in the Portland metropolitan area,
      the differential VE for the HD vaccine in preventing PCR-confirmed influenza
      hospitalization was assessed by a nested series of models across matching strata.
      For an exact match for high-dose and standard-dose seniors, matching elements
      included exact age, gender, residence type, race-ethnicity, provider bias, and
      residence area (zipcode). RESULTS: As a first step, a simple aggregate comparison
      of influenza-related hospitalization risk showed no added HD effectiveness. For
      the nested models, adding strata increased VE. In the final model, among 23,712
      matched pairs of HD to SD vaccinated seniors, the HD vaccine was 30.7% (95%CI: 8
      48%) more effective in preventing influenza-related hospitalization. CONCLUSION:
      For this study, the high-dose influenza vaccine provided superior protection for
      seniors against influenza hospitalization. Including matching elements as exact
      year of age and residence zipcode all added to the calculation of VE. As a
      warning, non-matched or overly simple matched VE study designs may substantially
      under-estimate VE.

PMID- 30287159
TI  - Inferior pseudo-hinge fulcrum technique and intraoperative complications of laser
      in situ keratomileusis retreatment after small-incision lenticule extraction.
AB  - PURPOSE: To describe the evolution of a flap-lift technique for laser in situ
      keratomileusis (LASIK) retreatment after small-incision lenticule extraction
      (SMILE) and report the incidence of complications. SETTING: London Vision Clinic,
      London, United Kingdom. DESIGN: Retrospective case series. METHODS: All
      retreatments between September 2013 and January 2017 were included. A bimanual
      inferior pseudo-hinge fulcrum flap-lift technique was developed to minimize the
      chance of tearing or entering the small incision. A flap lifter and a McPherson
      forceps were inserted into the inferior one third of the flap, slightly angled up
      to avoid perforating the small-incision lenticule extraction interface. One
      instrument provided countertraction, and the second separated the interface
      superiorly, keeping the tip away from the incision. One instrument was held
      against the hinge for the second instrument to separate the inferior one third.
      The incidence of intraoperative complications was analyzed. RESULTS: The study
      evaluated 162 retreatments (4.12%) for 3933 small-incision lenticule extraction
      treatments (1-year maturity). The retreatment was LASIK (n = 135), side-cut only
      (n = 1), cap-to-flap procedure (CIRCLE) (n = 3), or photorefractive keratectomy
      (n = 23). Two eyes (1.4%) had a tear to the small incision. The small-incision
      lenticule extraction interface was accessed in 8 eyes (5.8%), 1 (0.7%) centrally,
      and the interface was lifted in 1 eye (0.7%). There were no complications in the
      last 84 consecutive procedures (60%) using the finalized technique. CONCLUSION:
      The bimanual inferior pseudo-hinge fulcrum decreased the risk for accessing the
      small-incision lenticule extraction interface or tearing the small incision.

PMID- 30287158
TI  - Resting state functional connectivity in patients with remitted psychotic
      depression: A multi-centre STOP-PD study.
AB  - BACKGROUND: There is paucity of neurobiological knowledge about major depressive
      disorder with psychotic features ("psychotic depression"). This study addresses
      this knowledge gap by using resting state functional magnetic resonance imaging
      (R-fMRI) to compare functional connectivity in patients with psychotic depression
      and healthy controls. METHODS: We scanned patients who participated in a
      randomized controlled trial as well as healthy controls. All patients achieved
      remission from depressive and psychotic symptoms with sertraline and olanzapine.
      We employed Independent Component Analysis in independent samples to isolate the
      default mode network (DMN) and compared patients and controls. FINDINGS: The
      Toronto sample included 28 patients (mean [SD], age 56.2 [13.7]) and 39 controls
      (age 55.1 [13.5]). The Replication sample included 29 patients (age 56.1 [17.7])
      and 36 controls (age 48.3 [17.9]). Patients in the Toronto sample demonstrated
      decreased between-network functional connectivity between the DMN and bilateral
      insular, somatosensory/motor, and auditory cortices with peak activity in the
      right planum polare (t = 4.831; p = 0.001, Family Wise Error (FWE) corrected). A
      similar pattern of between-network functional connectivity was present in our
      Replication sample with peak activity in the right precentral gyrus (t = 4.144; p
      = 0.003, FWE corrected). INTERPRETATION: Remission from psychotic depression is
      consistently associated with an absence of increased DMN-related functional
      connectivity and presence of decreased between-network functional connectivity.
      Future research will evaluate this abnormal DMN-related functional connectivity
      as a potential biomarker for treatment trajectories. FUNDING: National Institute
      of Mental Health.

PMID- 30287161
TI  - Data-Mining Bioinformatics: Connecting Adenylate Transport and Metabolic
      Responses to Stress.
AB  - Adenine nucleotides are essential in countless processes within the cellular
      metabolism. In plants, ATP is mainly produced in chloroplasts and mitochondria
      through photophosphorylation and oxidative phosphorylation, respectively. Thus,
      efficient adenylate transport systems are required for intracellular energy
      partitioning between the cell organelles. Adenylate carriers present in different
      subcellular compartments have been previously identified and biochemically
      characterized in plants. Here, by using data-mining bioinformatics tools, we
      propose how, and to what extent, these carriers integrate energy metabolism
      within a plant cell under different environmental conditions. We demonstrate that
      the expression pattern of the corresponding genes is variable under different
      environmental conditions, suggesting that specific adenylate carriers have
      distinct and nonredundant functions in plants.

PMID- 30287160
TI  - Insulin-like Growth Factor (IGF)-1 treatment stabilizes the microvascular
      cytoskeleton under ischemic conditions.
AB  - Our previous studies showed that Insulin-like Growth Factor (IGF)-1 reduced blood
      brain barrier permeability and decreased infarct volume caused by middle cerebral
      artery occlusion (MCAo) in middle aged female rats. Similarly, cultures of
      primary brain microvessel endothelial cells from middle-aged female rats and
      exposed to stroke-like conditions (oxygen glucose deprivation; OGD) confirmed
      that IGF-1 reduced dye transfer across this cell monolayer. Surprisingly, IGF-1
      did not attenuate endothelial cell death caused by OGD. To reconcile these
      findings, the present study tested the hypothesis that, at the earliest phase of
      ischemia, IGF-1 promotes barrier function by increasing anchorage and stabilizing
      cell geometry of surviving endothelial cells. Cultures of human brain microvessel
      endothelial cells were subject to oxygen-glucose deprivation (OGD) in the
      presence of IGF-1, IGF-1 + JB-1 (IGFR inhibitor) or vehicle. OGD disrupted the
      cell monolayer and reduced cell-cell interactions, which was preserved in IGF-1
      treated cultures and reversed by concurrent treatment with JB-1. IGF-1-mediated
      preservation of the endothelial monolayer was reversed with LY294002 treatment,
      but not by Rapamycin, indicating that IGF-1 s actions on cell-cell contacts are
      likely mediated via the PI3K pathway. In vivo, microvessel morphology was
      evaluated in middle-aged female rats that were subjected to ischemia by MCAo, and
      treated ICV with IGFI, IGF-1 + JB-1, or artificial CSF (aCSF; vehicle) after
      reperfusion. Compared to vehicle controls, IGF-1 treated animals displayed larger
      microvessel diameters in the peri-infarct area and increased staining density for
      vinculin, an anchorage protein. Both these measures were reversed by concurrent
      IGF-1 + JB-1 treatment. Moreover these effects were restricted to 24 h after
      ischemia-reperfusion and no treatment effects were seen at 5d post stroke.
      Collectively, these data suggest that in the earliest hours during ischemia, IGF
      1 promotes receptor-mediated anchorage of endothelial cells, and its actions may
      be accurately characterized as vasculoprotective.

PMID- 30287162
TI  - How Soil Biota Drive Ecosystem Stability.
AB  - High biodiversity aboveground tends to increase the stability of ecosystem
      functioning when faced with a changing environment. However, whether and how soil
      biota affect ecosystem stability is less clear. Here, we introduce a framework
      for understanding the effects of soil biota on variation in ecosystem functioning
      under environmental changes. We conclude that soil biota may be a neglected
      factor determining ecosystem stability through their direct and indirect effects
      on plant diversity, the net productivity of an ecosystem, and compensatory
      dynamics among plant species, and via altering ecosystem resistance and
      resilience. Furthermore, future research needs to consider that effects of soil
      biota on ecosystem stability will vary depending on extrinsic factors, and for a
      given perturbation and ecosystem function.

PMID- 30287163
TI  - Damned by DNA - Balancing personal privacy with public safety.

PMID- 30287164
TI  - Law and policy oversight of familial searches in recreational genealogy
      databases.

PMID- 30287165
TI  - Bully victimization and child and adolescent health: new evidence from the 2016
      NSCH.
AB  - PURPOSE: To explore whether children with diagnosable health conditions are at
      greater risk of bully victimization and whether, among these children, bully
      victimization further elevates the risk of an array of health difficulties.
      METHODS: We examined a recent, nationally representative sample of children and
      adolescents aged 6-17 years who participated in the 2016 National Survey of
      Children's Health. Survey data pertaining to the children and adolescents
      covering bully victimization, health difficulties, and diagnosable health
      conditions were obtained from primary caregivers. RESULTS: The results suggest
      that children with diagnosable conditions are at significantly higher risk of
      being bullied, particularly among children with birth defects and developmental
      disorders (e.g., 50% or more are victims of bullying). Furthermore, the findings
      reveal that, among children with diagnosable conditions, those who are victims of
      bullying are significantly more likely to experience various health challenges,
      relative to nonvictims. While these findings are significant across age groups,
      12- to 17-year-old youth are more likely to experience bullying in the presence
      of multiple developmental disorders, and when this occurs, these youth are more
      likely to manifest health difficulties than younger children. CONCLUSIONS: The
      findings suggest that children with disabilities and chronic health conditions,
      who are at a significantly greater risk of being bullied, also suffer from
      further health difficulties when they are victimized by their peers. In
      conjunction with school-based interventions, primary care physicians may be
      ideally positioned to assess youth for victimization risk, provide counseling to
      youth victims, and reduce future victimization through office-based youth
      violence interventions.

PMID- 30287166
TI  - Response to "Criteria for spiritual support in critical care".

PMID- 30287167
TI  - Impact of preoperative sarcopenia on postoperative outcomes following pancreatic
      resection: A systematic review and meta-analysis.
AB  - BACKGROUND: Morphometric analysis of sarcopenia has garnered interest due to its
      putative role in predicting outcomes following surgery for a variety of
      pathologies, including resection for pancreatic disease. However, there are no
      standard recommendations on whether sarcopenia is a clinically relevant predictor
      of outcomes in this setting. The aim of this study was to review the prognostic
      impact of preoperatively diagnosed sarcopenia on postoperative outcomes following
      pancreatic resection. METHODS: A systematic review of published literature was
      performed using PRISMA guidelines, and included a search of PubMed, MEDLINE and
      SCOPUS databases until May 2018. RESULTS: Thirteen studies, including 3608
      patients, were included. There was a significant increase in the mean duration of
      post-operative hospital stay (mean difference of 0.73 days, CI: 0.06-1.40, P =
      0.033), there was no difference in the postoperative outcomes, including:
      clinically relevant postoperative pancreatic fistula, delayed gastric emptying,
      post-operative bile leak, surgical site infection, significant morbidity and
      overall morbidity. CONCLUSION: Preoperative sarcopenia is associated with
      prolonged hospital stay after pancreatic surgery. However, sarcopenia does not
      appear to be a significant negative predictive factor in postoperative morbidity
      although study heterogeneity and risk of bias limit the strength of these
      conclusions.

PMID- 30287168
TI  - Systemic chemotherapy in combination with liver-directed therapy improves
      survival in patients with pancreatic adenocarcinoma and synchronous liver
      metastases.
AB  - OBJECTIVES: We investigated whether the combination of systemic chemotherapy
      (SCT) and liver-directed therapy (LDT) was superior to chemotherapy alone for
      patients with pancreatic adenocarcinoma and synchronous liver metastases (PACLM).
      METHODS: We reviewed the medical records of 184 patients treated with SCT +/- LDT
      at Tianjin Medical University Cancer Hospital from 2001 to 2015. Overall survival
      (OS) was the primary end-point. The role of treatment modality and other clinical
      factors was evaluated by univariate and Cox regression analyses. RESULTS: Sixty
      four (34.8%) patients in the SCT-LDT group and 120 (65.2%) patients in the SCT
      group were included in the analysis. Baseline clinical characteristics were
      similar between the groups (all P > 0.05). The median survival was 8.7 months in
      the SCT-LDT group and was 6.3 months in the SCT group. The 0.5-, 1-, 2- and 3
      year survival rates were 67.2%, 33.4%, 13.3% and 8.9%, respectively, after SCT
      LDT, and were 54.9%, 19.0%, 4.5% and 2.0%, respectively, after SCT (P = 0.01).
      Primary tumor size, ascites, and treatment modality (SCT + LDT vs. SCT)
      independently predicted survival (P < 0.05). The clinical efficacy congruously
      favored the SCT-LDT group across the majority of subgroups. CONCLUSIONS: SCT
      combined with LDT was well tolerated and may be effective to improve survival of
      patients with PACLM. Ascites and large primary tumor size were poor prognostic
      factors associated with survival.

PMID- 30287169
TI  - Genetic Factors That Affect Spontaneous Clearance of Hepatitis C or B Virus,
      Response to Treatment, and Disease Progression.
AB  - Hepatitis C virus (HCV) and hepatitis B virus (HBV) infections can lead to
      cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Over the past
      decade, studies of individuals infected with these viruses have established
      genetic associations with the probability of developing a chronic infection, risk
      of disease progression, and likelihood of treatment response. We review genetic
      and genomic methods that have been used to study risk of HBV and HCV infection
      and patient outcomes. For example, genome-wide association studies have linked a
      region containing the interferon lambda genes to spontaneous and treatment
      induced clearance of HCV. We review the genetic variants associated with HCV and
      HBV infection, and how these variants affect specific expression or activities of
      their products. Further studies of these variants could provide insights into
      risk factors for and mechanisms of chronic infection and disease progression, as
      well as new strategies for treatment.

PMID- 30287170
TI  - Tropism for Spasmolytic Polypeptide-Expressing Metaplasia Allows Helicobacter
      pylori to Expand Its Intragastric Niche.
AB  - BACKGROUND & AIMS: In patients with chronic Helicobacter pylori infection,
      parietal and chief cell atrophy in the gastric corpus, a process known as
      spasmolytic polypeptide-expressing metaplasia (SPEM), increases the risk for
      progression to cancer. The relation between H pylori and these metaplastic
      changes is unclear. We investigated whether H pylori localizes to regions of
      SPEM. METHODS: We developed an in situ adherence assay in which we incubated H
      pylori with free-floating tissue sections from the gastric corpora of mice; we
      assessed H pylori distribution along the gastric unit by immunofluorescence. We
      analyzed the interactions of H pylori with tissue collected from mice with acute
      SPEM, induced by high-dose tamoxifen. We also evaluated how adhesin-deficient H
      pylori strains, chemical competition assays, and epithelial glycosylation
      affected H pylori adhesion to SPEM glands. We colonized mice with the mouse
      adapted PMSS1 strain and analyzed H pylori colonization in vivo during tamoxifen
      induced SPEM or after decrease of stomach acid with omeprazole. RESULTS: Compared
      with uninjured glands, H pylori penetrated deep within SPEM glands, in situ,
      through interaction of its adhesin, SabA, with sialyl-Lewis X, which expanded in
      SPEM. Helicobacter pylori markedly increased gastric corpus colonization when
      SPEM was induced, but this proximal spread reversed in mice allowed to recover
      from SPEM. Decreasing corpus acidity also promoted proximal spread. However, H
      pylori penetrated deep within corpus glands in vivo only when sialyl-Lewis X
      expanded during SPEM. CONCLUSIONS: Helicobacter pylori differentially binds SPEM
      glands in situ and in mice, in large part by interacting with sialyl-Lewis X. Our
      findings indicate that H pylori expands its niche into the gastric corpus by
      promoting and exploiting epithelial metaplastic changes that can lead to
      tumorigenesis.

PMID- 30287171
TI  - Targeted and Immune-based Therapies for Hepatocellular Carcinoma.
AB  - Treatment options for patients with hepatocellular carcinoma (HCC) are rapidly
      changing based on positive results from phase 3 trials of targeted and immune
      based therapies. More agents designed to target specific pathways and immune
      checkpoints are in clinical development. Some agents have already been shown to
      improve outcomes of patients with HCC, as first- and second-line therapies, and
      are either awaiting approval by the Food and Drug Administration or have been
      recently approved. We summarize the targeted and immune-based agents in trials of
      patients with advanced HCC and discuss the future of these strategies for liver
      cancer.

PMID- 30287172
TI  - Identifying normal embryos from reciprocal translocation carriers by whole
      chromosome haplotyping.

PMID- 30287173
TI  - Serum anti-Mullerian hormone concentration before and after salpingectomy for
      ectopic pregnancy.
AB  - RESEARCH QUESTION: Does salpingectomy for ectopic pregnancy affect the ovarian
      reserve measured by changes in pre- and post-operative levels of anti-Mullerian
      hormone (AMH)? DESIGN: This is a prospective observational multicentre study of
      64 women treated with salpingectomy for an ectopic pregnancy. AMH was measured in
      serum samples collected at admission before salpingectomy and at follow-up
      (median time to follow-up [interquartile range] was 3 [3-4] months). Changes in
      serum AMH levels were investigated using Wilcoxon signed-rank test and the
      relationship between changes in AMH and age, time to follow-up, and pre-operative
      serum AMH level was investigated using linear regression analysis. The biological
      variation of AMH was also calculated. RESULTS: Serum AMH levels did not differ
      significantly before and after salpingectomy (median ?AMH [follow-up value minus
      admission value] 0.40 pmol/l, interquartile range -2.0 to 4.0 pmol/l). DeltaAMH
      was independent of age, time to follow-up and pre-operative serum AMH level. The
      intra-individual biological variation for AMH ranged from 12.1% to 26.3%,
      depending on time between the two samples. CONCLUSIONS: This is the first paired
      study to investigate serum AMH values before and after salpingectomy in an
      unselected population of women presenting with an ectopic pregnancy, including
      both patients who conceived naturally and following fertility treatment. It was
      found that salpingectomy for ectopic pregnancy had no short-term effect on serum
      AMH levels, and changes in AMH levels were independent of age, time to follow-up,
      and pre-operative serum AMH level. Furthermore, the study demonstrated a 6-month
      biological variation of AMH of less than 30%.

PMID- 30287174
TI  - Label-free detection of pepsinogen 1 and 2 by polyethylene coating Lamb
      microfluidic device.
AB  - Early screening of gastric cancer is a critical importance for the improvement of
      patients' survival rate. Here, a polyethylene coating Lamb (PE-Lamb) microfluidic
      device with immune layer for gastric cancer label-free detection was constructed.
      Two serum pepsinogen 1 (PG1) and pepsinogen 2 (PG2) biomarkers were applied to
      screen and predict the appearance of gastric cancer. Compared with enzyme-linked
      immunosorbent assay (ELISA), this method achieved a higher sensitivity and less
      time (40 min vs 120 min). The limit of detections (LOD) were reached 60 pg/mL for
      PG1 and 30 pg/mL for PG2, which have two orders of magnitude lower than
      traditional ELISA. The linearity coefficient indexes (R2) for PG1 and PG2 were
      0.992 and 0.953 respectively, which is similar to that of ELISA. In addition, PG1
      and PG2 mixed antigens sample with human serum was detected by PE-Lamb approach,
      and the frequency response showed high reproducibility and specificity. The
      results indicate that PE-lamb diagnostic technique is a novel and promising
      method for high-throughput screening and early diagnosis of gastric cancer.

PMID- 30287175
TI  - Development and application of a novel electrochemical immunosensor for
      tetracycline screening in honey using a fully integrated electrochemical Bio
      MEMS.
AB  - Tetracycline (TC) is a veterinary drug, wildly prescribed for prophylactic and
      therapeutic purposes. Consequently, its remaining residues in food products have
      to be regularized. We report in this paper about the development of a novel
      immunosensor based on an integrated bio micro-electromechanical system (Bio-MEMS)
      containing eight gold microelectrodes (uWEs), an integrated silver and platinum
      reference and counter electrodes, respectively. TC immobilization on the uWEs
      surface was conducted using three methods. The first through functionalization
      with 4-aminophenylacetic acid (CMA), the second by functionalization with CMA
      followed by preconcentration of a new structure of magnetic nanoparticles (MNPs)
      coated with poly (pyrrole-co-pyrrole-2-carboxylic acid) (Py/Py-COOH/MNPs) cross
      linked with Ab-TC, and the last one directly through the functionalization with
      Py/Py-COOH/MNPs. The analyte was quantified by competitive detection with TC
      immobilized on the uWEs surface toward specific polyclonal antibody (Ab-TC),
      using a mixture of a fixed concentration of Ab-TC and decreasing levels of TC one
      from 0.1 pg mL-1 to 1000 pg mL-1. Microcontact printing, followed by fluorescence
      microscopy characterization were performed during the functionalization of the
      immunosensor surface to certify that the corresponding immune detection process
      is taking place. This immunosensor was found to be highly sensitive with a limit
      of detection of 1.2 pg mL-1 and specific in the presence of interferents. The
      standard addition method was exploited to detect TC in honey samples. The present
      immunosensor platform is up-and-coming for TC detection which can dramatically
      decrease the time of analysis providing a new pathway for advanced immunoassays
      development in industrial food control.

PMID- 30287176
TI  - Gingko flap: The development of a novel flap technique to reduce dog ear
      formation.

PMID- 30287177
TI  - The integration of inflammaging in age-related diseases.
AB  - Aging is characterized by a morpho-functional adaptation, variably affecting
      major physiological systems, depending on a complex interaction between genetic,
      environmental and stochastic factors. This dynamic interaction drives an age
      related remodelling of a number of pathways/systems, providing the chance to
      reach the extreme limit of human life in healthy state which is reflected in the
      ever-increasing number of centenarians. This conceptualization implies that aging
      process per se and the development of the most common age-related diseases (ARD)
      are somewhat separate but must share somehow common set of basic biological
      mechanisms. One of the features that characterize both processes is the
      development and progression of an inflammatory state named inflammaging. Notably,
      inflammaging is characterized by a peculiar presentation, being a chronic,
      systemic, low grade and therefore for a long time subclinical, inflammatory
      process. For these reasons, even if the rate of progression of inflammaging is
      currently recognized as the main force driving aging and one of the main risk
      factors for clinical morbidity and mortality in the elderly, current knowledge on
      the causal agents are still incomplete and the "clinical evaluation" of
      inflammaging has not yet been standardized. Even if a number of biomarkers of
      inflammaging have been identified, their analysis is not recommended as part of
      the routine evaluation of elderly patients. This review will aim to describe the
      concept of inflammaging within several other concepts such as the definition of
      aging per se and how we integrate it in the context of ARD.

PMID- 30287178
TI  - The Impact of Breast Density Reporting Laws on Women's Awareness of Density
      Associated Risks and Conversations Regarding Supplemental Screening With
      Providers.
AB  - OBJECTIVE: We conducted a national survey to understand the impact of state-level
      density reporting laws on women's level of density risk awareness and their
      engagement in conversations with providers regarding supplemental screening.
      METHODS: In all, 1,500 US women aged 40 to 74 years who obtained a mammogram
      within 2 years were surveyed in February 2018. The sampling design yielded 300
      respondents in each of five groups categorized based on density reporting law
      features. Women were asked about their breast density-related knowledge,
      importance of being notified, and sources of information and if conversations
      with providers regarding density and supplemental screening occurred. Survey
      results were compared across groups and between women residing in states with
      versus without density laws. RESULTS: The majority of respondents in all groups
      felt that it is important for women to know their breast density type (range, 85%
      90%). Women were most likely informed of breast density type by a health care
      provider (range, 68%-72%), followed by the mammography result letter (range, 48%
      68%), and then a radiologist (range, 46%-61%). Women from states with a density
      law were significantly more likely to have learned of their breast tissue type
      from a mammogram results letter (60% versus 48%, P = .011) and discuss
      supplemental screening (67% versus 53%, respectively; P = .008) than women from
      states without a law. CONCLUSION: State-level density reporting laws are
      associated with increased breast density awareness and increased likelihood of
      conversations between women and their providers regarding supplemental screening.

PMID- 30287179
TI  - Ultrasound-assisted oil-in-water nanoemulsion produced from Pereskia aculeata
      Miller mucilage.
AB  - For the preparation of nanoemulsions, the correct choice of emulsifiers, together
      with the emulsification methods, directly influences the final product quality.
      The present study reports the ultrasound-assisted preparation of oil-in-water
      nanoemulsions produced with mucilage extracted from leaves of Pereskia aculeata
      Miller (ora-pro-nobis; OPN). The OPN mucilage (%) and soybean oil (%)
      concentration range, and the process operating parameters, ultrasonic power
      amplitude (%) and sonication time (min), were optimized based on the mean droplet
      diameter (d32). The effect of the mucilage and oil concentrations was also
      investigated by the response variables such as polydispersity, density,
      turbidity, viscosity, zeta-potential, and interfacial tension. The higher OPN
      mucilage concentrations (%) with lower amounts of soybean oil (%) favored
      nanoemulsion formations (116 <= d32 <= 171 nm) and increased polydispersity,
      density, and zeta-potential. On increasing OPN mucilage and soybean oil the
      turbidity of the dispersions increased. All colloidal systems showed Newtonian
      behavior, and the viscosity in the systems increased due to the greater OPN
      mucilage concentration in the aqueous phase at a certain oil concentration. In
      addition, lower values of equilibrium interfacial tension were found with
      increasing OPN mucilage concentrations. Finally, from the stability test, it can
      be pointed out that the OPN mucilage concentration should be between 1.0 and 1.5%
      and the oil concentration should be less than 5%, so that lower d32 values are
      maintained over time. Therefore, mucilage extracted from OPN and the ultrasound
      technique can be used in the preparation of nanoemulsions.

PMID- 30287180
TI  - Ultrasound-assisted synthesis of two-dimensional layered ytterbium substituted
      molybdenum diselenide nanosheets with excellent electrocatalytic activity for the
      electrochemical detection of diphenylamine anti-scald agent in fruit extract.
AB  - Metal chalcogenides with large active sites have been received great attention as
      an excellent catalyst due to their hierarchical structural properties. Here, we
      have demonstrated the synthesis of ytterbium-doped molybdenum selenide (YbMoSe2)
      in the form of two-dimensional nanosheets by using a simple ultrasonic method.
      The formation of the crystal phase of prepared YbMoSe2 nanosheets was studied by
      using the selective characterization techniques. The reported HRTEM confirmed
      that the introduction of heterogeneous spin of Yb with MoSe2 creates the lattice
      distortion. Thus, the active sites can be increased by creating the lattice
      distortion on the basal plane of the metal chalcogenides nanosheets. The band gap
      study was carried out by using UV-visible spectrometer and demonstrated the
      decreasing band gap of MoSe2 from 1.30 eV to 1.15 eV due to the Yb
      substitution/doping. The increasing active sites with decreasing band gap
      facilitate an excellent electronic conductivity and electrochemical activity.
      Furthermore, the electrocatalytic activity of YbMoSe2 modified glassy carbon
      electrode (YbMoSe2/GCE) toward the sensing of diphenylamine (DPA) anti-scald
      agent. As expected, YbMoSe2/GCE showed a high level of electrochemical activity
      with a low limit of detection (0.004 uM) and excellent sensitivity (11.4 uA uM-1
      cm-2) towards the detection of DPA. In addition, the superior selectivity,
      stability, and reproducibility of YbMoSe2/GCE also were recorded. The beneficial
      electrochemical activity of YbMoSe2/GCE offered the more advantages to detection
      of DPA in the food sample also.

PMID- 30287181
TI  - Ultrasonically formation of supramolecular based ultrasound energy assisted
      solidification of floating organic drop microextraction for preconcentration of
      methadone in human plasma and saliva samples prior to gas chromatography-mass
      spectrometry.
AB  - In this work, an ultrasonic-assisted supramolecular based on solidification of
      floating organic drop microextraction (UA-SM-SFO-ME) was developed as a green
      method for preconcentration of methadone prior to gas chromatography-mass
      spectrometry (GC-MS). The supramolecular solvent aggregates containing reverse
      micelles of 1-dodecanol in tetrahydrofuran (THF) were formed by ultrasonication
      that subsequently dispersed in the sample solution. Ultrasonic waves caused the
      fast formation of supramolecular solvent aggregates. In this work,
      ultrasonication was used in two phases: First phase, the formation of reverse
      micelles and the second phase, the dispersion of supramolecular solvent in the
      sample solution. Actually, ultrasonication was basic of this presented work. In
      order to provide the highest extraction efficiency, the influence of various
      parameters on the method performance (supramolecular solvent type and volume,
      disperser solvent condition, pH, extraction time and salt concentration) was
      investigated. Based on the obtained optimum conditions, the limits of detection
      (LODs) and the limits of quantitation (LOQs) were obtained 0.5-1.2 ug L-1 and 1.2
      2.5 ug L-1 with preconcentration factors in the range of 182-191, in water and
      biological samples, respectively. Subsequently, the method was assessed for
      preconcentration of the methadone in human plasma and saliva samples.

PMID- 30287182
TI  - Factors associated with bariatric surgery utilization among eligible candidates:
      who drops out?
AB  - BACKGROUND: Bariatric surgery is underutilized. OBJECTIVES: To identify factors
      associated with eligible patient dropout from bariatric surgery. SETTING:
      University hospital, United States. METHODS: Eligible candidates were identified
      after a multidisciplinary review committee (MRC) of all patients (n = 484) who
      attended a bariatric surgery informational session (BIS) at a single-center
      academic institution in 2015. We compared patients who underwent surgery within 2
      years of BIS with those who did not (i.e., dropped out) by evaluating patient,
      insurance, and program-specific variables. Univariate analyses and multivariable
      regressions were performed to identify factors associated with patient dropout
      among eligible candidates. RESULTS: We identified 307 (63%) patients who
      underwent MRC. Thirty-three (11%) patients were deemed poor candidates and
      surgery was not recommended. Among eligible candidates, 82 (30%) dropped out from
      the program. Factors independently associated with eligible patient dropout
      included coronary artery disease (odds ratio [OR] .13 [.02-.66]; P = .014),
      hypertension (OR .46 [.24-.87]; P = .017), time from BIS to MRC (OR .99 [.99
      .99]; P = .002), 3 months of medically supervised weight loss documentation (OR
      .09 [.02-.51]; P = .007), endocrinology clearance (OR .26 [.09-.76]; P = .014),
      hematology clearance (OR .37 [.14-.95]; P = .039), urine drug screen testing (OR
      .31 [.13-.72]; P = .006), additional psychological evaluation (OR .43 [.20-.93];
      P = .031), and required extra sessions with the dietician (OR .39 [.17-.92]; P =
      .032). Thirty-three (6.8%) patients underwent surgery at another institution, and
      42% of these patients lived more than 50 miles from attended BIS site.
      CONCLUSIONS: Twenty-seven percent of patients did not undergo bariatric surgery
      at their initial site of evaluation despite being considered eligible candidates
      after MRC. Dropout was independently associated with patient, insurance, and
      program-specific variables that may represent barriers to care amenable to
      improvement.

PMID- 30287183
TI  - Intravenous and Inhaled Milrinone in Adult Cardiac Surgery Patients: A Pairwise
      and Network Meta-Analysis.
AB  - OBJECTIVE: To summarize the evidence on the hemodynamic, echocardiographic, and
      clinical effects of inhaled and intravenous milrinone (iMil and IvMil) in adult
      cardiac surgery patients. DESIGN: Systematic review, pairwise and network meta
      analysis. SETTING: Multi-institutional. PARTICIPANTS: Adult cardiac surgery
      patients. INTERVENTIONS: Comparison between iMil and IvMil versus other agents or
      placebo. MEASUREMENTS AND MAIN RESULTS: The primary endpoints were mean pulmonary
      artery pressure (MPAP) and peripheral vascular resistance (PVR). Secondary
      endpoints included the following: (1) mean arterial pressure, heart rate, and
      cardiac index (CI); (2) echocardiographic data; and (3) clinical outcomes. Random
      model, leave-one-out-analysis, and meta-regression were used. Thirty studies (6
      iMil and 24 IvMil) were included for a total of 1,438 patients (194 iMil and 521
      IvMil). IvMil was associated with a lower MPAP, lower PVR, and higher CI compared
      to placebo (standardized mean difference [SMD] = -0.22 [95% CI = -0.48 to 0.05],
      SMD = -0.49 [95% CI = -0.71 to -0.27], and SMD = 0.94 [95% CI = 0.51 to 1.37]).
      No difference in any outcome was found between iMil and placebo. At network meta
      analysis, significantly lower PVR and shorter hospital length of stay were found
      for IvMil compared to iMil (SMD = -0.82 [95% CI = -1.53 to -0.10] and SMD = -0.50
      [95% CI = -0.95 to -0.05], respectively). CONCLUSION: These results support the
      clinical use of IvMil in cardiac surgery patients. No evidence at present
      supports the adoption of iMil.

PMID- 30287184
TI  - Increased age and proton pump inhibitors are associated with severe Clostridium
      difficile infections in children.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is increasing in children. We
      aimed to compare the clinical characteristics between CDI and colonization and to
      identify the risk factors for severe diseases of CDI in children. METHOD: We
      retrospectively reviewed 124 children (1-18 years old) from 2011 to 2018. CDI was
      defined as diarrhea (>=3 loose stool in the past 24 h) with confirmed toxigenic
      strain. Colonization was defined as presence of C. difficile without clinical
      symptoms. Severe diseases included ileus, acute kidney injury, gastrointestinal
      bleeding or mortality. Patients younger than 1 year old and coinfections with
      other enteric pathogens were excluded. RESULTS: Among 124 patients with C.
      difficile identified, 49 of them fulfilled CDI definition and 75 had C. difficile
      colonization. Children with CDI were more likely to present with watery (74% vs.
      1%, p < 0.01) and mucoid stool (25% vs. 7%, p < 0.01) and occult blood in stool
      (67% vs. 33%, p < 0.01) than children with colonization. In CDI cases, elevated
      age-adjusted creatinine (18% vs. 0%, p = 0.03) and hyponatremia (134 mEq/L vs.
      137 mEq/L, p = 0.04) were found. Also, they had more complicated diseases (27%
      vs. 0%, p < 0.01). On multivariate analysis, age older than 4 years (adjusted
      odds ratio: 5.83; 95% confidence interval: 1.05-32.27) and proton pump inhibitor
      use (PPI) (adjusted odds ratio: 7.25; 95% confidence interval: 1.07-49.07) were
      the independent factors for severe diseases. CONCLUSIONS: Watery diarrhea, mucoid
      stool and occult blood in stool could differentiate CDI from colonization.
      Patients with increased age and previous PPI use were the independent risk
      factors for severe diseases in children.

PMID- 30287185
TI  - A severe combined immunodeficiency disease mouse model of human adenocarcinoma
      with lepidic-predominant growth.
AB  - Severe combined immunodeficiency disease (SCID) mice with human lepidic
      adenocarcinoma were established by the intrabronchial implantation of fresh
      surgically resected specimens. Human pulmonary adenocarcinoma tissue from 16
      different cases was transplanted into SCID mice, and SCID mouse tumors were
      established from four of these cases (25%). Among the four tumors, the tumor
      cells of two SCID mice showed replacement lepidic growth of mouse alveolar
      structures accompanied by multiple intrapulmonary lesions. Human lung carcinoma
      cell lines showing lepidic growth are rare and the xenograft models using the
      SCID mouse model developed in the current study will be useful for analyzing the
      growth and/or progression patterns and clinical behavior of lepidic
      adenocarcinoma, the major histological subtype of human carcinoma of the lung.

PMID- 30287186
TI  - Antimicrobial activity of solithromycin and levofloxacin against a murine
      pneumonia mixed-infection model caused by Streptococcus pneumoniae and anaerobic
      bacteria.
AB  - INTRODUCTION: Solithromycin is a novel fluoroketolide developed to treat
      pneumonia. But, few studies evaluating its antimicrobial activity against S.
      pneumoniae in a mixed-infection model with anaerobes are available, while
      community-acquired pneumonia can involve mixed-infection of Streptococcus
      pneumoniae and anaerobic bacteria. This study evaluated the antimicrobial
      activity of solithromycin against macrolide-resistant S. pneumoniae and anaerobic
      bacteria with a murine pneumonia mixed-infection model. MATERIAL AND METHODS: We
      evaluated antimicrobial activity of solithromycin (10 and 20 mg/kg) and
      levofloxacin (126 mg/kg) against S. pneumoniae with a three-point mutation in
      penicillin-binding protein and an ermB gene, and Parvimonas micra. Antimicrobial
      efficacy was calculated for each isolate as the change in bacterial count
      (Deltalog10 CFU/mL) obtained in the treated mice after 24 h compared with the
      count in the starting control animals. RESULTS: The solithromycin and
      levofloxacin minimum inhibitory concentrations (MICs) for S. pneumoniae were 0.03
      and 0.5 MUg/mL, respectively. The solithromycin and levofloxacin MICs for P.
      micra were 0.015 and 0.12 MUg/mL, respectively. In a mixed-infection model,
      solithromycin showed significantly higher antimicrobial activity against S.
      pneumoniae than levofloxacin (solithromycin 20 mg/kg; -2.87 +/- 1.33 log10 CFU/mL
      vs. levofloxacin; -1.35 +/- 0.37 log10 CFU/mL, p = 0.0397). Similarly,
      solithromycin showed significantly higher antimicrobial activity against P. micra
      than levofloxacin (solithromycin 20 mg/kg; -2.78 +/- 0.98 log10 CFU/mL vs.
      levofloxacin; -1.57 +/- 0.47 log10 CFU/mL, p = 0.0400). DISCUSSION: Solithromycin
      showed higher antimicrobial activities against macrolide-resistant S. pneumoniae
      and P. micra than levofloxacin, even though they were coexisted in murine lung
      tissue. Our results suggest that solithromycin could be effective for pneumonia
      patients due to S. pneumoniae to reduce bacterial density in lung tissue.

PMID- 30287187
TI  - The involvement of estrogen receptors alpha and beta in the in vitro effects of
      17beta-estradiol on secretory profile of peritoneal macrophages from naturally
      menopausal female and middle-aged male rats.
AB  - The systemic and extra- gonadal levels of 17beta-estradiol (E2) change during
      aging, and affect the expression of estrogen receptors (ERs) in the immune cells
      of both females and males. The age-related cessation of ovarian function in
      females, as well as the tissue-specific expression of enzyme aromatase (estrogen
      synthase which significantly rises with the advancing age) in both males and
      females, both determine the concentration of E2 to which immune cells may be
      exposed. The present study was set up to investigate the direct influence of E2
      in vitro on the secretory profile of peritoneal macrophages from young and
      naturally menopausal female rats, and from young and middle-aged male rats. The
      involvement of receptor(s) responsible for mediating the effects of E2 in vitro
      was examined by use of antagonists specific for ERalpha or ERbeta. Whereas in
      macrophages from young female rats E2 treatment diminished interleukin (IL)-1beta
      secretion, it increased it in young males, and the middle-aged females. The in
      vitro E2 treatment increased tumor necrosis factor (TNF)-alpha release by
      macrophages from young rats of both sexes, while it increased macrophage IL-6
      release independently of both sex and age. At the same time, E2 decreased
      hydrogen peroxide (H2O2) production in macrophages from females, and increased it
      in male rats of both ages, whereas it diminished nitric oxide (NO) release in all
      experimental groups. Inspite of the sex- and age-specific effects of E2 on
      macrophage urea release, E2 did not affect the NO/urea ratio in macrophages from
      female rats, and diminished it in macrophages from both young and middle-aged
      male rats. Independently of the sex and age, E2 stimulated the release of
      inflammatory cytokines predominantly via macrophage ERalpha, and inhibited the IL
      1beta release in young females via ERbeta. In contrast, E2 increased macrophage
      H2O2 and urea production by activating ERbeta, but diminished their release via
      ERalpha. Our study may contribute to better understanding of the complex role(s)
      that E2 may play in innate immunity during aging, and that are dependent of sex.

PMID- 30287188
TI  - Magnetic Resonance Angiography in Pulmonary Embolism: A Review.

PMID- 30287189
TI  - Enhanced antimicrobial, antioxidant, in vivo antitumor and in vitro anticancer
      effects against breast cancer cell line by green synthesized un-doped SnO2 and Co
      doped SnO2 nanoparticles from Clerodendrum inerme.
AB  - A novel approach was employed for the synthesis of un-doped tinoxide and Cobalt
      doped tinoxide (Co-doped SnO2) nanoparticles (NAPs) by using aqueous extract of
      Clerodendrum inerme with the help of eco-friendly superficial solution combustion
      method. Synthesized NAPs were characterized by different spectroscopic techniques
      and results from XRD, TEM, SEM, EDX and UV-Vis examines confirmed the successful
      synthesis, crystalline nature and spherical structure of un-doped SnO2 and Co
      doped SnO2 NAPs with the average grain size of 30 and 40 nm; and band gap energy
      of 3.68 and 2.76 eV respectively. Antimicrobial propensity of the synthesized
      NAPs was determined by agar well assay, SEM, TEM and confocal laser scanning
      microscopic analysis against various bacterial and fungal strains. Synthesized Co
      doped SnO2 NAPs were unveiled the extraordinary antibacterial and antifungal
      activities against E. coli, B. subtilis, A. niger, A. flavus, and C. albicans
      with the zone of inhibitions of 30 +/- 0.08 mm and 26 +/- 0.06 mm, 17 +/- 0.04
      mm, 23 +/- 0.08 mm and 26 +/- 0.06 respectively which were also evidenced from
      SEM, TEM and confocal laser scanning microscopy. In addition, green synthesized
      Co-doped SnO2 NAPs were demonstrated the substantial antioxidant activity by
      scavenging DPPH, significant in vitro anticancer and in vivo antitumor activity
      on breast carcinoma cells (MCF-7) and Ehrlich ascites tumor cell lines
      respectively than standard. The hemolytic activity disclosed low cytotoxicity of
      fabricated NAPs (0.89 +/- 0.05%) at 5 mg/mL, which was indicated their
      biocompatibility potential. Hence, the multi-purpose properties of synthesized
      NAPs presented in the current study can be further deliberated for pharmaceutical
      and nanomedicine applications.

PMID- 30287190
TI  - Cortisol responses of goldfish (Carassius auratus) to air exposure, chasing, and
      increased water temperature.
AB  - Fish can respond to stimuli from the internal or external environment with
      activation of the hypothalamo-pituitary-interrenal (HPI) axis and the secretion
      of cortisol. Stimuli that activate the HPI axis of fish include short term air
      exposure and increases in water temperature. The present study was conducted to
      determine how quickly cortisol concentrations increase in goldfish subjected to
      an increase in water temperature, and to compare the response to an increase in
      water temperature with responses to other stimuli. Plasma cortisol concentrations
      varied widely between individual goldfish, with concentrations ranging from 9.1
      to 516.0 ng/mL in goldfish on the day of arrival from the supplier. Mean cortisol
      concentrations in undisturbed goldfish were low (4.5 +/- 1.0 ng/mL). Mean
      cortisol concentrations in fish exposed to air for 3 min and in fish that
      experienced chasing for 10 min were markedly elevated 15 min after the beginning
      of the stimuli (132.6 +/- 31.0 and 121.1 +/- 23.9 ng/mL respectively). Mean
      cortisol concentrations in fish that experienced an increase in water temperature
      rose to 22.2 +/- 7.6 ng/mL after 15 min, declined to <10 ng/mL at 30 and 60 min
      then increased and were elevated (79.0 +/- 10.8 ng/mL) at 240 min. Cortisol
      measurements can be used to indicate the responsiveness of fish to changes in
      water temperature and goldfish will be a convenient study species for the
      development of studies of plasticity in responses of fish to increases in water
      temperature that are happening due to climate change.

PMID- 30287191
TI  - The use of hair cortisol for the assessment of stress in animals.
AB  - The hair cortisol concentration (HCC) is assumed to be a retrospective marker of
      integrated cortisol secretion and stress over longer periods of time. Its
      quantification is increasingly used in psychoneuroendocrinological studies in
      humans, but also in animal stress and welfare research. The measurement of HCCs
      for the assessment of stress offers many considerable benefits for use in
      domesticated and wild animals, especially due to the easy and minimally invasive
      sampling procedure and the representation of longer time periods in one sample.
      This review aims to outline the different fields of application and to assess the
      applicability and validity of HCC as an indicator for chronic stress or long-term
      activity of the hypothalamic-pituitary-adrenal axis in wild and domesticated
      animals. Specific hair characteristics are presented and the advantages and
      limitations of using HCC are discussed. An overview of findings on the impact of
      stress- and health-related factors on HCCs and of diverse influencing factors
      causing variation in hair cortisol levels in different species is given.
      Recommendations for the use of hair cortisol analysis are proposed and potential
      fields of future research are pointed out. The studies indicate an effect of age
      and pregnancy on HCCs, and cortisol incorporation into hair was also found to
      depend on hair colour, body region, sex and season of year, but these results are
      less consistent. Furthermore, the results in animals show that a wide array of
      stressors and pathological conditions alters the cortisol concentrations in hair
      and that HCC thereby provides a reliable and valid reflection of long-term
      cortisol secretion in many species. However, more research is necessary to
      investigate the underlying mechanisms of cortisol incorporation into the hair and
      to explore the hair growth characteristics in the species of interest. To
      overcome confounding influences, the use of standardized sampling protocols is
      strongly advised.

PMID- 30287192
TI  - The utility of motor unit number index: A systematic review.
AB  - The need for a valid biomarker for assessing disease progression and for use in
      clinical trials on amyotrophic lateral sclerosis (ALS) has stimulated the study
      of methods that could measure the number of motor units. Motor unit number index
      (MUNIX) is a newly developed neurophysiological technique that was demonstrated
      to have a good correlation with the number of motor units in a given muscle, even
      though it does not necessarily accurately express the actual number of viable
      motor neurons. Several studies demonstrated the technique is reproducible and
      capable of following motor neuron loss in patients with ALS and peripheral
      polyneuropathies. The main goal of this review was to conduct an extensive review
      of the literature using MUNIX. We conducted a systematic search in English
      medical literature published in two databases (PubMed and SCOPUS). In this
      review, we aimed to answer the following queries: Comparison of MUNIX with other
      MUNE techniques; the reproducibility of MUNIX; the utility of MUNIX in ALS and
      preclinical muscles, peripheral neuropathies, and other neurological disorders.

PMID- 30287193
TI  - Vagus nerve stimulation promotes generalization of conditioned fear extinction
      and reduces anxiety in rats.
AB  - BACKGROUND: Exposure-based therapies are used to treat a variety of trauma- and
      anxiety-related disorders by generating successful extinction following cue
      exposure during treatment. The development of adjuvant strategies that accelerate
      extinction learning, improve tolerability, and increase efficiency of treatment
      could increase the efficacy of exposure-based therapies. Vagus nerve stimulation
      (VNS) paired with exposure can enhance fear extinction, in rat models of
      psychiatric disorders, and chronic administration of VNS reduces anxiety in rats
      and humans. OBJECTIVE: We tested whether VNS, like other cognitive enhancers,
      could produce generalization of extinction for stimuli that are not presented
      during the extinction sessions, but are associated with the fear event. METHODS:
      Male Sprague Dawley rats underwent auditory fear conditioning with two easily
      discriminable auditory stimuli. Following fear conditioning, extinction training
      consisted of exposure to only one of the conditioned sounds. Half of the rats
      received VNS and half received sham stimulation during with sound presentations.
      VNS effects on anxiety were examined in a separate study where VNS was
      administered prior to testing on the elevated plus maze. RESULTS: Sham stimulated
      rats given 20 presentations of a conditioned stimulus (CS) during the extinction
      session showed performance that was matched to VNS-treated rats given only 4
      presentations of the CS. Despite comparable levels of freezing to the presented
      CS, only the VNS-treated rats showed a significant decrease in freezing to the CS
      that was not presented. VNS-induced generalization of extinction was observed
      only when the two sounds were paired with footshock within the same fear
      conditioning session; VNS did not promote generalization of extinction when the
      two sounds were conditioned on different days or in different contexts. On the
      anxiety test, VNS administration significantly increased time spent in the open
      arms of the elevated plus maze. CONCLUSION: These results provide evidence that
      VNS can promote generalization of extinction to other stimuli associated with a
      specific fear experience. Furthermore, non-contingent VNS appears to reduce
      anxiety. The ability to generalize extinction and reduce anxiety makes VNS a
      potential candidate for use as an adjunctive strategy to improve the efficacy and
      tolerability of exposure-based therapies.

PMID- 30287194
TI  - The flavonoid acetylpectolinarin counteracts the effects of low ethanol on
      spontaneous network activity in hippocampal cultures.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: A major concern in modern society involves the
      lasting detrimental behavioral effects of exposure to alcoholic beverages.
      Consequently, hundreds of folk remedies for hangover have been suggested, most of
      them without a scientific basis, for lack of proper test systems. Over centuries,
      yellow toadflax (Linaria vulgaris Mill., Lv) tincture has been used in Russian
      traditional medicine to treat the spectrum of hangover symptoms such as vertigo,
      headache, drunken behaviors, and as a sedative. MATERIALS AND METHODS: Here we
      use in-vitro cultured hippocampal neurons to examine the effect of the Lv extract
      as well as the flavonoid acetylpectolinarin (ACP) exclusively found in Lv
      extract, on spontaneous network activity of the cultured neurons exposed to low,
      physiological concentrations of ethanol. RESULTS: As in previous studies, low
      (0.25-0.5%) ethanol causes an increase in network activity, which was converted
      to suppression, with high concentrations of ethanol. Lv extract and ACP, at low
      concentrations, had no appreciable effect on spontaneous activity, but they
      blocked the facilitating action of low ethanol. This action of ACP was also seen
      when the culture was exposed to 1-EBIO, a SK potassium channel opener, and was
      blocked by apamin, an SK channel antagonist. In contrast, ACP or Lv extracts did
      not reverse the suppressive effects of higher ethanol. CONCLUSIONS: Our results
      suggest that ACP acts by interacting with the SK channel, to block the
      facilitatory effect of low concentration of ethanol, on network activity in
      hippocampal cultures.

PMID- 30287195
TI  - Rosmarinus officinalis essential oil: A review of its phytochemistry, anti
      inflammatory activity, and mechanisms of action involved.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Plant species Rosmarinus officinalis L.
      (Lamiaceae; Synonyms: Salvia rosmarinus Schleid. and Rosmarinus angustifolius
      Mill.) is a herb widely used worldwide. In local and traditional medicine, its
      used for inflammation-related diseases. Currently, studies report anti
      inflammatory activity in its essential oil (EORO). However, to better understand
      EORO's anti-inflammatory activity its necessary to understand its phytochemistry
      and the signaling pathways affected by it. Hence, this review aimed to describe
      EORO phytochemical profile, ethnopharmacological uses, some biological activities
      of EORO will be described but emphasizing its anti-inflammatory potential and
      possible mechanisms of action involved. MATERIALS AND METHODS: The research was
      performed using the databases Medline, Embase, BVS Regional Portal, Science
      Direct, CAPES Journals, and Scopus; using the keywords "Rosmarinus officinalis",
      "anti-inflammatory" and "essential oil". Additional information was gathered from
      related textbooks, reviews, and documents. RESULTS AND DISCUSSION: Until now
      about 150 chemical compounds were identified in EORO samples, more frequently
      reported molecules were 1,8-cineole, alpha-pinene, and camphor. Studies suggest
      that the anti-inflammatory activity of EORO occur mainly through inhibition of NF
      kappaB transcription and suppression of arachidonic acid cascade. Its antioxidant
      activity also aids by preventing injury caused by the reactive species of
      inflammation; its smooth muscle relaxant activity contributes to ameliorating
      airway inflammatory diseases. Lastly, toxicity assessments indicate low toxicity
      to EORO. CONCLUSIONS: Current evidence indicates anti-inflammatory activity in
      EORO, supporting its ethnopharmacological uses in inflammatory-related diseases,
      and potential future applications. However, although considerable acute
      inflammatory models were tested, more chronic inflammatory models are needed;
      clinical studies are still absent, this may be due to the high doses needed for
      essential oils to exert pharmacological effects, but recent studies show this
      issue can be bypassed using the oil formulated as nanoemulsions to improve its
      bioavailability.

PMID- 30287196
TI  - Cytotoxicity of Luffa cylindrica (L.) M.Roem. extract against circulating cancer
      stem cells in hepatocellular carcinoma.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Luffa cylindrica (L.) M.Roem. has been recognized
      as traditional medicine for the treatment of various diseases like inflammatory
      diseases, diarrhea and viral infections. The usual parts used include fruit,
      seeds and leaves. AIM OF THE STUDY: To evaluate the anticancer activity of the
      hot water extract of the whole plant of Luffa cylindrica using circulating tumor
      cells and cancer stem cells isolated from the peripheral blood of hepatocellular
      carcinoma patients in vitro. MATERIALS AND METHODS: Seventy five adult patients
      who reported as stage II and III Hepatocellular carcinoma were selected. Blood
      samples were withdrawn and the circulating tumor cells were isolated from the
      whole blood. Tumor cells and cancer stem cells were detected and isolated by flow
      cytometric techniques. The isolated cell types were cultured and propagated in
      the tissue culture facility, the extract was tested on the isolated cells.
      RESULTS: Luffa cylindrica hot water extract has shown cytotoxic activity against
      circulating tumor cells of hepatocellular carcinoma especially the cells sub
      population CD133+/CD44+ with little effect among CD133+/CD44- sub-population.
      CONCLUSION: Hot water extract of Luffa cylindrica whole plant could decrease the
      ratio of cancer stem cells in blood of HCC patients and may be used to minimize
      recurrence and metastasis in hepatocellular carcinoma patients.

PMID- 30287197
TI  - Are polyphenol antioxidants at the root of medicinal plant anti-cancer success?
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Given the severe side effects associated with
      most of the conventional cancer medications, as well as the expanding body of
      evidence indicating secondary toxicity of these drugs, individuals with cancer
      are increasingly turning to natural alternatives. Similarly, the pharmaceutical
      industry is in search of natural products to treat cancer. An understanding of
      the specific active components in plant products with which anti-cancer efficacy
      is achieved is required for this research to move forward. AIM OF THE STUDY: To
      integrate data from cancer-relatestudies on plant-derived products or extracts,
      to elucidate whether these products may have similar active ingredients and/or
      mechanisms of action, that can explain their efficacy. This review also includes
      a discussion of the methodological complexities and important considerations
      involved in accurate isolation and characterisation of active substances from
      plant material. CONCLUSIONS: From the literature reviewed, most plant products
      with consistently reported anti-cancer efficacy contains high levels of
      polyphenols or other potent antioxidants and their mechanisms of action correlate
      to that reported for isolated antioxidants in the context of cancer. This
      suggests that natural products may indeed become the panacea against this chronic
      disease - either as therapeutic medicine strategy or to serve as templates for
      the design of novel synthetic drugs. The recommendation is made that antioxidant
      activity of plant actives and especially polyphenols, should be the focus of anti
      cancer drug discovery initiatives. Lastly, researchers are advised to exploit
      current techniques of chemical compound characterisation when investigating
      polyphenol-rich plants to enable the easy consolidation of research findings from
      different laboratories.

PMID- 30287198
TI  - A Systematic Review of Training in Symptom Management in Palliative Care Within
      Postgraduate Medical Curriculums.
AB  - CONTEXT: Symptom management is a priority area within palliative care core
      competencies for generalist providers. Although several educational initiatives
      exist, a comprehensive evidence synthesis on the effectiveness of symptom
      management training on trainees' learning and patient-reported outcomes is
      lacking. OBJECTIVES: The objective of this study was to determine the
      effectiveness of training in symptom management in palliative care providers in
      nonpalliative specialties. METHODS: This is a systematic review following Best
      Evidence Medical Education methods from searches of MEDLINE, EMBASE, ERIC,
      CINAHL, PsycINFO, Cochrane database of systematic, Clinical Trials.gov, and
      ISRCTN databases to September 2017. Prospective controlled studies testing the
      impact of symptom management educational interventions on physicians in training
      in nonpalliative specialties were included. Data were summarized narratively,
      grouped by curriculum description, and effectiveness on trainees' learning or
      patient-reported outcomes. RESULTS: Of 5062 records identified, six studies met
      the inclusion criteria: two randomized controlled trials and four quasi
      experimental. Pain management and use of opioids and their side effects were most
      frequently covered. Clinical decision support tools, Web-based teaching,
      palliative care rotation, and mixed educational methods were used. Most studies
      used self-reported, original, or modified evaluation instruments, although
      psychometric properties were seldom reported. Despite methodological
      considerations, all educational methods improved trainees' learning outcomes.
      However, the effects on trainees' behavior and patient-related outcomes were not
      evaluated. CONCLUSION: Current educational training programs in symptom
      management appear to improve trainees' comfort, preparedness, and knowledge in
      assessing and managing patients' symptoms at the end of life. More rigorous
      research to evaluate the impact of this training on residents and organizational
      performance is now required.

PMID- 30287199
TI  - Society of Hematologic Oncology State of the Art Update and Next Questions:
      Multiple Myeloma.
AB  - During the past decade, the survival outcomes of patients with multiple myeloma
      (MM) have dramatically improved, not only owing to the advent of a number of
      novel therapies, but also to the deepening insight regarding how to best use
      these options. Triplet-based induction regimens can yield overall response rates
      of <= 100%. In the relapsed and refractory setting, we have a multitude of
      doublet and triplet options available with high and durable response rates. The
      addition of monoclonal antibodies has provided a new class of agents to augment
      our standard approach with novel therapies. Minimal residual disease status
      testing has worked its way into the lexicon of the myeloma-treating physician and
      provides both prognostic and potentially therapeutic insight into management.
      Despite the influx of novel therapies, high-dose melphalan with autologous stem
      cell rescue remains a vital tenet of induction therapy for our younger and more
      fit patients. The current generation of clinical trials using immunologic
      approaches such as bifunctional antibodies and chimeric antigen receptor T cells
      is extremely promising and will likely become the future standard of care.
      Although the disease remains, on the whole, incurable, we now possess therapeutic
      modalities that can provide deep and durable remissions and, potentially, cure
      for some.

PMID- 30287200
TI  - Role of Proteasome Inhibitors in Relapsed and/or Refractory Multiple Myeloma.
AB  - Proteasome inhibition is an established treatment strategy for patients with
      multiple myeloma as proteasome inhibitors (PIs) selectively target and disrupt
      the protein metabolism of aberrant plasma cells. Since the introduction of the
      first-in-class PIs bortezomib, the therapeutic landscape for multiple myeloma has
      shifted with the development of next-generation PIs (carfilzomib and ixazomib)
      and new classes of agents. Treatment with modern combination therapies has been
      shown to result in deep responses and improved outcomes, and these potent
      regimens are increasingly used as frontline therapy. As patients continue to live
      longer with modern frontline therapy, there will be an increased need for
      effective regimens after initial treatment failure. Several recent studies have
      shown that treatment with combination therapy incorporating PIs induces deep and
      durable responses in patients with relapsed and/or refractory multiple myeloma.
      In this review, we review pivotal data and discuss the role of PIs-based doublet
      and triplet regimens for the management of relapsed/refractory multiple myeloma
      in the era of modern combination therapy.

PMID- 30287201
TI  - Systematic neglect of men as a key population in tuberculosis.

PMID- 30287202
TI  - Autologous platelet-rich fibrin: can it secure a better healing?
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of platelet-rich
      fibrin (PRF) in the healing of impacted mandibular third molar (M3) extraction
      sockets. STUDY DESIGN: This study included 30 patients with bilaterally symmetric
      impacted M3 (N = 60) requiring transalveolar extraction. All patients were
      assigned numbers randomly; left-sided M3 patients with odd numbers and right
      sided patients with even numbers were categorized into group A (test group), and
      the other side of the mouth was classified as "group B" (control group). Group A
      M3 extraction sockets received PRF, whereas group B sockets were closed without
      PRF. Patients were evaluated for pain and swelling on postoperative days 1, 3, 7,
      and 14. Bone healing was compared on postoperative weeks 8 and 16. Analysis of
      variance (ANOVA) and Tukey's multiple comparison tests were applied for
      statistical analysis. RESULTS: A total of 30 patients, ages 18 to 40years,
      participated in this study. The overall postoperative pain score (visual analogue
      scale [VAS]) and facial swelling percentages were lower for group A compared with
      group B (P < .05). Early bone healing was also evident on postoperative
      radiographs obtained at weeks 8 and 16 in group A (P < .001). CONCLUSIONS: The
      use of autologous PRF aids in earlier and better wound healing in a controlled
      manner.

PMID- 30287203
TI  - Early detection of cherubism with eventual bilateral progression: a literature
      review and case report.
AB  - Cherubism is a rare familial disease of childhood that commonly affects the
      bilateral mandible and maxilla and typically resolves in adulthood. It has been
      shown to have a male predilection and has been mapped to the SH3 BP2 gene. Only 2
      cases of unilateral cherubism have been documented in the literature; in the
      first case, the contralateral side was eventually affected. Although rare,
      unilateral cherubism presents a diagnostic dilemma. This case report describes a
      unique presentation of unilateral cherubism that progressed to affect the
      contralateral side and describes some of the considerations in the diagnosis and
      treatment of unilateral benign giant cell lesions of the jaws.

PMID- 30287204
TI  - Analytical polyphosphate extraction from Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, inorganic polyphosphate is analyzed by polyphosphate
      extraction and subsequent quantification. Recently, we developed a method for
      polyphosphate quantification, and length determination of short chain
      polyphosphate. However, the lack of a simple, optimized and validated method for
      analytical polyphosphate extraction has both hindered the advance in this
      research field, and prevented comparability of results between laboratories.
      Hence, the goal of this study was to develop an analytical method for
      polyphosphate extraction from S. cerevisiae. Several literature methods were
      compared with special attention to omission of polyphosphate precipitation steps,
      because these work neither at low polyphosphate concentrations nor
      quantitatively. The best literature protocol, which takes 5.5 h and requires five
      reaction tubes per sample, was optimized here in regards to the amount of
      extracted polyphosphate and simplification of the work flow. The final protocol
      extracts 40 % more polyphosphate than the best literature method, takes only 30
      min, requires just one reaction tube per sample, and is, therefore, proposed as
      the new gold standard for analytical polyphosphate extraction from S. cerevisiae.
      In combination with our recently published polyphosphate quantification method,
      total polyphosphate in S. cerevisiae can now be analyzed within 2 h.

PMID- 30287205
TI  - A bare covered stent.

PMID- 30287206
TI  - Thrombosis in a Massive Varix.

PMID- 30287207
TI  - Venous Leg Ulcer Clinical Practice Guidelines: What is AGREEd?
AB  - OBJECTIVE/BACKGROUND: The aim was to evaluate the quality of current venous leg
      ulcer (VLU) clinical practice guidelines (CPGs) to assist healthcare
      professionals in choosing an accessible high quality CPG to advise their
      practice, and to identify areas for improvement in future versions of current
      CPGs. METHODS: A systematic review of PubMed, Embase, online CPG databases, and
      reference lists of included CPGs was carried out. Full text CPGs published no
      earlier than 1998 reporting evidence based recommendations on VLU diagnosis and
      management in English were included. CPGs that were only available if purchased
      were excluded. Two reviewers identified eligible CPGs, extracted data, and
      assessed the quality independently using the Appraisal of Guidelines for Research
      and Evaluation II (AGREE II) instrument. Significant scoring discrepancies were
      discussed with a third reviewer. RESULTS: Fourteen eligible CPGs were identified
      (1999-2016). The majority of CPGs originated from Europe or North America.
      Overall, there was good inter-reviewer reliability of scores with an intraclass
      correlation coefficient of 0.986 (95% confidence interval 0.979-0.991). No single
      CPG achieved the highest score in all six domains. Significant methodological
      heterogeneity was observed across VLU CPGs; however, consistently, poor
      performance was noted in domain 5, concerning CPG applicability. CONCLUSION: Four
      CPGs were considered of adequate quality for clinical use. Consolidation of
      efforts to drive high quality, comprehensive VLU CPGs is necessary to reduce the
      number of and heterogeneity seen in currently published guidelines. Elements of
      methodological quality are lacking and a structured approach with use of
      checklists and CPG creation tools, such as AGREE II or others, may bolster rigour
      in future VLU CPGs.

PMID- 30287208
TI  - Site and Burden of Lower Limb Atherosclerosis Predicts Long-term Mortality in a
      Cohort of Patients With Peripheral Arterial Disease.
AB  - OBJECTIVE/BACKGROUND: Lower limb peripheral arterial disease (PAD) is becoming
      increasingly common. Lower limb perfusion, as determined by the ankle brachial
      pressure index (ABPI), is a recognised predictor of overall mortality. The
      increasing role of non-invasive imaging in patient assessment may aid in the
      ability to predict poor patient outcomes. METHODS: This study included all
      patients undergoing a lower limb arterial duplex over a period of 20 months. The
      site and burden of atherosclerosis within the lower limb was determined using the
      well validated Bollinger score. Patient demographic data were also collated. The
      primary outcome measure was all cause mortality. RESULTS: A total of 678 patients
      were included (median age 74 years). The overall median follow up period was 69.9
      months. Of these, 307 patients reached the primary end point, which was death.
      Independent predictors of all cause mortality included total Bollinger score
      (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.18 [p < .001]; OR per
      10 points), femoropopliteal Bollinger score (OR 1.34, 95% CI 1.11-1.08 [p = .05];
      OR per 10 points), and crural Bollinger score (OR 1.03, 95% CI 1.01-1.03 [p =
      .03]). There was also a significant association between mortality and age, a
      prior history of ischaemic heart disease, a history of congestive cardiac failure
      and chronic renal failure (chronic kidney disease >= 3). Statin and antiplatelet
      therapy were protective. CONCLUSION: This contemporary study confirms poor long
      term outcomes still exist in patients with PAD. The site and severity of lower
      limb atherosclerosis are independent predictors of long-term mortality.

PMID- 30287209
TI  - Nonagenarians will be the Future Challenge for Vascular Specialists.

PMID- 30287210
TI  - Alirocumab dosing patterns during 40 months of open-label treatment in patients
      with heterozygous familial hypercholesterolemia.
AB  - BACKGROUND: ODYSSEY OLE (NCT01954394) was an open-label extension (OLE) study for
      patients with heterozygous familial hypercholesterolemia (HeFH) who had completed
      previous phase 3 clinical trials with alirocumab. Alirocumab dose could be
      increased or decreased as per physician judgment. OBJECTIVE: To assess how the
      alirocumab dosing strategy was used by physicians during OLE. METHODS: Patients
      who entered OLE on a starting dose of alirocumab 75 mg every 2 weeks (Q2W) were
      included in the analysis (those from FH I, FH II, and LONG TERM trials). Those
      who completed LONG TERM entered an 8-week washout period before receiving
      alirocumab 75 mg Q2W at the start of OLE. From week 12, dose adjustment from 75
      to 150 mg Q2W, or vice versa, was possible, based on the physician's clinical
      judgment. RESULTS: In total, 909 patients with HeFH completed the 3 parent
      studies and were treated during OLE for a duration of up to 40 months. Most
      patients (56.7%) were maintained on 75 mg Q2W throughout OLE, whereas 43.3% of
      patients had their dose increased to 150 mg Q2W. The dose was subsequently
      decreased in 7.4% of the patients in whom alirocumab was initially uptitrated.
      Overall, treatment-emergent adverse events were similar between those who had
      received placebo or alirocumab in the parent studies. CONCLUSIONS: In the opinion
      of physicians, alirocumab 75 mg Q2W enabled over half of patients with HeFH to
      achieve sufficient low-density lipoprotein cholesterol lowering.

PMID- 30287211
TI  - Alcohol-Dependent Pulmonary Inflammation: A Role for HMGB-1.
AB  - Previous studies demonstrate that acute alcohol intoxication significantly
      impairs lung immune responses, which can lead to the tissue undefended from
      microbial infection and resulting disease. Data suggest that acute intoxication
      presents an axis where simultaneously suppressing early pro-inflammatory
      cytokines while inducing anti-inflammatory signals contribute to alcohol
      dependent immune suppression in the lung, and thus undeterred microbial
      replication. Interestingly, alcoholics and those with alcohol use disorder
      present with increased pneumonia and Acute Respiratory Disease (ARDs), suggesting
      a more active priming of inflammatory responses in the lungs. There is current
      research evaluating the acute effects of binge ethanol consumption on adolescents
      and is of grave concern, though long-term effects of adolescent ethanol binge
      exposure is less studied. We hypothesize that adolescent binge drinking may prime
      the individual to severe pulmonary distress, when later challenged by a microbial
      pathogen. Herein, we evaluate a model of Adolescent Intermittent Ethanol (AIE)
      exposure to investigate pulmonary pathology after microbial challenge. Ethanol
      (EtOH) was administered to adolescent mice using a binge exposure schedule and
      then rested to early adulthood. These mice were then challenged with a sub-lethal
      intra-nasal inoculation of K. pneumoniae and evaluated for severity of disease.
      We find that AIE exposure initially activates inflammatory mediators within the
      lung, which resolves over time. However when challenged with a microbial pathogen
      after this resolution period, these animals present with more severity of
      inflammation, pulmonary tissue damage and mortality when challenged with a
      pulmonary microbial infection. Interestingly, our data suggests a role for
      alcohol-dependent release of the protein HMGB-1 from host cells, for both
      morbidity and mortality in our model of microbial-dependent pulmonary
      inflammation.

PMID- 30287212
TI  - HIV/SIV-Nef: Pas de trois Choreographies to Evade Immunity.
AB  - Nef is a major pathogenic factor of human and simian immunodeficiency viruses
      that hijacks protein trafficking through physical interaction with vesicle coats.
      This alters the subcellular localization of proteins involved in immunity and
      neutralizes their function. Understanding the structural bases for these
      interactions could reveal new targets for antiviral intervention.

PMID- 30287213
TI  - Colchicine reduces platelet aggregation by modulating cytoskeleton rearrangement
      via inhibition of cofilin and LIM domain kinase 1.
AB  - INTRODUCTION: Platelets activation/aggregation with subsequent thrombus formation
      is the main event in the pathophysiology of acute coronary syndrome. Once
      activated, platelets show an extensive cytoskeleton rearrangement that leads to
      recruitment of additional platelets to finally cause haemostatic plug formation.
      Thus, the cytoskeleton plays a pivotal role in this phenomenon. Colchicine (COLC)
      is an anti-inflammatory drug proven to reduce major cardiovascular events in
      patients with coronary artery disease. The molecular mechanisms by which COLC
      exerts these protective effects remain partially still unknown. Since COLC causes
      disruption of tubulin, a component of cell cytoskeleton, we investigated whether
      this drug might interfere with platelet aggregation by acting on cytoskeleton
      rearrangement. METHODS AND RESULTS: Platelets isolated from healthy volunteers
      were activated with Adenosine Diphosphate (ADP, 20 MUM) Collagen (COLL, 60
      MUg/ml) and Thrombin Activating Receptor Peptide (TRAP 25 MUM) with/without COLC
      10 MUM pretreatment. After stimulus, aggregation was measured by light
      aggregometry overtime. Microtubules structure was assessed by
      immunohistochemistry and key proteins involved in regulation of actin-filament
      assembly and contractility such as Myosin Phosphatase Targeting subunit (MYPT),
      LIM domain kinase 1(LIMK1) and cofilin were evaluated by Western Blot analysis.
      Colchicine pretreatment significantly blunted ADP/COLL/TRAP-induced platelet
      aggregation (up to 40%). COLC effects appeared mediated by microtubules
      depolymerization and cytoskeleton disarrangement associated to inactivation of
      MYPT and LIMK1 that finally interfered with cofilin activity. CONCLUSIONS: Our
      data indicate that colchicine exerts anti-platelet effects in vitro via
      inhibition of key proteins involved in cytoskeleton rearrangement, suggesting
      that its beneficial cardiovascular properties may be due, at least in part, to an
      inhibitory effect of platelet activity.

PMID- 30287214
TI  - Association between pregnant women's experience of stress and partners' fly-in
      fly-out work.
AB  - BACKGROUND: It is relatively common in Western Australia for men to commute long
      distances and work away from home for extended periods of time, often referred to
      as fly-in-fly-out work. Women are particularly susceptible to the effects of
      stress during pregnancy, and the absence of a partner due to working away could
      be an additional risk to their wellbeing. While there is little published fly-in
      fly-out literature, there is evidence that working non-standard hours, more
      generally, has a negative impact on health and well-being of workers and their
      families. AIM: To determine if there is an association between pregnant women's
      report of stress and their partners working fly-in-fly-out, and if so, is there
      is a differential impact that is dependent on family socioeconomic status.
      METHODS: Data from a Western Australian pregnancy cohort study were analysed
      (n=394 families). Couples completed self-report ratings of anxiety, depression,
      stress, family functioning, and stressful life events. Comparisons were made
      between three groups: fly-in-fly-out workers, non-fly-in-fly-out regular schedule
      workers, and non-fly-in-fly-out irregular schedule workers. RESULTS: After
      controlling for a range of variables, women's stress was significantly associated
      (p<.05) with their partners working fly-in-fly-out. Neither women's education,
      partners' occupation nor an interaction between partners' fly-in-fly-out work and
      partners' occupation were significantly associated with women's stress.
      CONCLUSION: There is some evidence that the pregnant partners of fly-in-fly-out
      workers perceive their lives to be more stressful than women whose partner works
      non-fly-in-fly-out regular schedules.

PMID- 30287215
TI  - Transcatheter aortic valve replacement outcomes in bicuspid compared to
      trileaflet aortic valves.
AB  - AIM: TAVR in patients with bicuspid aortic valves (BAV) is more challenging
      compared to individuals with trileaflet aortic valves (TAV). BAV have been
      excluded from the large randomized clinical trials assessing transcatheter aortic
      valve replacements (TAVR) and has been considered as a relative contraindication
      to TAVR. To report the outcomes of TAVR in BAV and compare them to TAV in the
      National Inpatient Sample (NIS). METHODS AND RESULTS: TAVR procedures were
      identified between 2011 and 2014 in the NIS dataset. Endpoints assessed included
      in-hospital mortality, periprocedural complications, length of stay and cost. Of
      40,604 identified TAVR procedures, 407 (1%) were BAV and the 40,197 (99%) were
      TAV. Patients with BAV were younger and had a lower comorbidity burden. In
      hospital mortality (4.89% vs 4.17%, OR: 1.71, 95%CI: 0.57-5.12, P = 0.21), AMI
      (3.49% vs 3.58%, OR: 1.12, 95%CI: 0.36-3.54, P = 0.85), stroke and TIA (2.49% vs
      3.55%, OR: 0.75, 95%CI: 0.18-3.16, P = 0.70), vascular complications (2.39% vs
      5.58%, OR:0.47, 95%CI: 0.11-1.93, P = 0.29), major bleeding (16.96% vs 23.50%,
      OR: 0.63, 95%CI: 0.34-1.17, P = 0.15) and rates of permanent pacemaker (PPM)
      (9.88% vs 10.88%, OR: 1.19, 95%CI: 0.57-2.51, P = 0.64) were similar in both
      cohorts. CONCLUSIONS: With multimodality imaging and further improvement in
      technology, our study demonstrates off-label TAVR should not be considered
      prohibitive and can be successfully performed for BAV with similar peri
      procedural outcomes compared to those with TAV. However, there is a need for
      robust large prospective studies.

PMID- 30287217
TI  - Editorial: The science to improve neonatal delivery room resuscitation.

PMID- 30287216
TI  - Nano-TiO2 stability in medium and size as important factors of toxicity in
      macrophage-like cells.
AB  - TiO2 along with nano-TiO2 are commonly found in consumer products. In vivo
      studies have observed an accumulation of nano-TiO2 in macrophages. However,
      characteristics of nano-TiO2 determining toxicity remain unclear. In our study,
      the cytotoxic effects of 14 diverse nano-TiO2 on THP-1 macrophage-like cells were
      measured by 3 cytotoxicity assays (MTS, WST-1 and LDH). Total averaged
      cytotoxicity was calculated using principal component analysis. Characteristics
      of all 14 nano-TiO2 included hydrodynamic diameter, zeta potential, shape,
      polydispersity index (PDI) and concentration; moreover, crystal form, specific
      surface area and crystallite size were measured for 10 nano-TiO2.The variables
      affecting cytotoxicity were chosen using LASSO (least absolute shrinkage and
      selection operator). Except for concentration, PDI in media measured within 1 h
      after preparation of the nanomaterial dispersion was selected as a variable
      affecting cytotoxicity: stable dispersion resulted in higher cytotoxic effects.
      Crystallite size has been shown to have nonlinear effects (particles of sizes
      between 20 and 60 nm were cytotoxic while smaller and larger ones were not) and
      thus it has been excluded from LASSO. The shape (particles/fibre) and crystal
      form did not affect the cytotoxicity. PDI and the nonlinear effect of size could
      be an explanation for the inconsistencies of the cytotoxicity of nano-TiO2 in
      various studies.

PMID- 30287218
TI  - A text mining analysis of medication quality related event reports from community
      pharmacies.
AB  - BACKGROUND: Medication errors are estimated to cost $42 billion in annual global
      treatment costs. Pharmacy-based Patient Safety Organizations (PSO) are tasked
      with collecting and analyzing incidents, near misses, and unsafe condition
      reports as one way of engaging pharmacies in quality improvement efforts.
      Collectively, these reports are referred to as quality related events (QREs).
      Large-scale analysis of typed narratives from QRE reports across organizations
      has been a missing component of quality improvement programs. OBJECTIVE: To
      identify topics within the components of a proposed medication safety event
      framework contained in the free-text narrative of QRE reports. METHODS: A
      retrospective, observational analysis of data from a PSOs voluntary reporting
      system, from January 1, 2011 to December 31, 2014. The dataset contained
      structured and unstructured data elements. A structural topic model extracted
      themes from the free-text narrative component of the report. These topics were
      assigned a human label and mapped onto constructs of the medication safety event
      framework. RESULTS: A total of 531,555 QREs were analyzed from 1660 pharmacies.
      90.6% were near miss and unsafe condition reports. There were 40 topics
      generated. There were 29 topics identified as QRE types, 3 were identified as
      contributing factors, and 5 were related to signals/alerts that an incident or
      near miss had occurred. One topic each was identified as a recovery step and a
      quality improvement strategy. One topic was not assigned a human label. Examples
      of topics labeled included incorrect tapering directions, needing to double-check
      work, and attention-related contributing factor. CONCLUSIONS: The free-text
      narrative provided novel information compared to the structured fields of the
      reports. Topics were mapped onto a proposed medication safety event framework to
      advance knowledge of medication QREs and identify ways to improve medication
      safety in community pharmacy. Future work may focus on communicating these topics
      to the pharmacies to improve medication safety efforts.

PMID- 30287219
TI  - The heterogeneity of autoimmune polyendocrine syndrome type 1: Clinical features,
      new mutations and cytokine autoantibodies in a Brazilian cohort from tertiary
      care centers.
AB  - Autoimmune polyendocrine syndrome type 1 (APS1) is characterized by multiorgan
      autoimmunity. We aim at characterizing a multi-center Brazilian cohort of APS1
      patients by clinical evaluation, searching mutation in the AIRE gene, measuring
      serum autoantibodies, and investigating correlations between findings. We
      recruited patients based on the clinical criteria and tested them for AIRE
      mutations, antibodies against interferon type I and interleukins 17A, 17F and 22.
      We identified 12 unrelated families (13 patients) with typical signs of APS1 in
      the proband, and the screening of relatives recognized an asymptomatic child.
      Candidiasis was present in all cases, and 19 other manifestations were observed.
      All patients carried one of 10 different mutations in AIRE, being 3 new ones, and
      were positive for anti-interferon type I serum antibody. Anti-interleukin-17A
      levels inversely correlated with the number of manifestations in each patient.
      This negative correlation may suggest a protective effect of anti-interleukin-17A
      with a potential therapeutic application.

PMID- 30287220
TI  - Low density lipoprotein oxidation by ferritin at lysosomal pH.
AB  - Oxidation of low density lipoprotein (LDL) has been proposed to be involved in
      the pathogenesis of atherosclerosis. We have previously shown that LDL can be
      oxidised by iron in lysosomes. As the iron-storage protein ferritin might enter
      lysosomes by autophagy, we have investigated the ability of ferritin to catalyse
      LDL oxidation at lysosomal pH. LDL was incubated with ferritin at 37  degrees C
      and pH 4.5 and its oxidation monitored spectrophotometrically at 234 nm by the
      formation of conjugated dienes and by measuring oxidised lipids by HPLC or a tri
      iodide assay. Iron released from ferritin was measured using the ferrous iron
      chelator bathophenanthroline and by ultrafiltration followed by atomic absorption
      spectroscopy. LDL was oxidised effectively by ferritin (0.05-0.2 MUM). The
      oxidation at lysosomal pH (pH 4.5) was much faster than at pH 7.4. Ferritin
      increased cholesteryl linoleate hydroperoxide, total lipid hydroperoxides and 7
      ketocholesterol. Iron was released from ferritin at acidic pH. The iron
      chelators, diethylenetriaminepentaacetate and EDTA, and antioxidant N,N'-diphenyl
      p-phenylenediamine inhibited the oxidation considerably, but not entirely. The
      antioxidant tempol did not inhibit the initial oxidation of LDL, but inhibited
      its later oxidation. Cysteamine, a lysosomotropic antioxidant, inhibited the
      initial oxidation of LDL in a concentration-dependent manner, however, the lower
      concentrations exhibited a pro-oxidant effect at later times, which was
      diminished and then abolished as the concentration increased. These results
      suggest that ferritin might play a role in lysosomal LDL oxidation and that
      antioxidants that accumulate in lysosomes might be a novel therapy for
      atherosclerosis.

PMID- 30287221
TI  - The deuridylylation activity of Herbaspirillum seropedicae GlnD protein is
      regulated by the glutamine:2-oxoglutarate ratio.
AB  - The nitrogen metabolism of Proteobacteria is controlled by the general Ntr system
      in response to nitrogen quality and availability. The PII proteins play an
      important role in this system by modulating the cellular metabolism through
      physical interaction with protein partners. Herbaspirillum seropedicae, a
      nitrogen-fixing bacterium, has two PII proteins paralogues, GlnB and GlnK. The
      interaction of H. seropedicae PII proteins with its targets is regulated by
      allosteric ligands and by reversible post-translational uridylylation. Both
      uridylylation and deuridylylation reactions are catalyzed by the same
      bifunctional enzyme, GlnD. The mechanism of regulation of GlnD activity is still
      not fully understood. Here, we characterized the regulation of deuridylylation
      activity of H. seropedicae GlnD in vitro. To this purpose, fully modified PII
      proteins were submitted to kinetics analysis of its deuridylylation catalyzed by
      purified GlnD. The deuridylylation activity was strongly stimulated by glutamine
      and repressed by 2-oxoglutarate and this repression was strong enough to overcome
      the glutamine stimulus of enzymatic activity. We also constructed and analyzed a
      truncated version of GlnD, lacking the C-terminal regulatory ACT domains. The
      GlnDDeltaACT protein catalyzed the futile cycle of uridylylation and
      deuridylylation of PII, regardless of glutamine and 2-oxoglutarate levels. The
      results presented here suggest that GlnD can sense the glutamine:2-oxoglutarate
      ratio and confirm that the ACT domains of GlnD are the protein sensors of
      environment clues of nitrogen availability.

PMID- 30287222
TI  - Interplay between alpha-synuclein amyloid formation and membrane structure.
AB  - Amyloid formation is a pathological hallmark of many neurodegenerative diseases,
      including Alzheimer's, Parkinson's, and Huntington's. While it is unknown how
      these disorders are initiated, in vitro and cellular experiments confirm the
      importance of membranes. Ubiquitous in vivo, membranes induce conformational
      changes in amyloidogenic proteins and in some cases, facilitate aggregation.
      Reciprocally, perturbations in the bilayer structure can be induced by amyloid
      formation. Here, we review studies in the last 10 years describing alpha
      synuclein (alpha-syn) and its interactions with membranes, detailing the roles of
      anionic and zwitterionic lipids in aggregation, and their contribution to
      Parkinson's disease. We summarize the impact of alpha-syn - comparing monomeric,
      oligomeric, and fibrillar forms - on membrane structure, and the effect of
      membrane remodeling on amyloid formation. Finally, perspective on future studies
      investigating the interplay between alpha-syn aggregation and membranes is
      discussed. This article is part of a Special Issue entitled: Amyloids.

PMID- 30287224
TI  - Impact of Multifocality and Multilocation of Positive Surgical Margin After
      Radical Prostatectomy on Predicting Oncological Outcome.
AB  - OBJECTIVE: To assess the impact of focality and location of positive surgical
      margins (PSM) on long-term outcomes after radical prostatectomy (RP) for prostate
      cancer (PCa), including biochemical recurrence (BCR), metastasis and overall
      mortality. PATIENTS AND METHODS: From a total of 2796 cases of RP between 1993
      and 2007 in our single hospital, 476 cases with PSMs were identified and included
      in this study. PSM location was categorized into apex, peripheral, and bladder
      neck. Survival was estimated using the Kaplan-Meier method. Cox proportional
      hazard regression models were used to analyze the impact of PSM focality and
      location status on oncologic survival. RESULTS: Of these 476 cases with PSMs, 335
      (70.4%) cases were with single focal (sF) PSMs and 141 (29.6%) cases were with
      multifocal (mF) PSMs. Furthermore, 406 (85.3%) cases were found to have single
      location (sL) PSMs, and 70 (14.7%) cases were with multilocation (mL) PSMs. The
      median follow-up was 12.9 years. mF-PSMs and mL-PSMs showed significant impact on
      increased BCR risk on univariate analysis, and mL-PSMs remained significant on
      multivariate analysis (P = .048). Furthermore, the combination of multifocality
      and multilocation showed added prognostic value on predicting BCR-free survival,
      but not on metastasis-free survival or overall survival. CONCLUSION: The presence
      of mF-PSMs and mL-PSMs, and especially the combination of both, demonstrated
      significant impact on BCR prognosis. Patients with apex sLsF-PSMs were less
      likely to have BCR when compared with all those with non-apex sLsF-PSMs. These
      results should be considered when evaluating patients for adjuvant therapy.

PMID- 30287223
TI  - Updated Recommendations on the Diagnosis, Management, and Clinical Trial
      Eligibility Criteria for Patients With Renal Medullary Carcinoma.
AB  - Renal medullary carcinoma (RMC) is one of the most aggressive renal cell
      carcinomas. It predominantly afflicts young adults and adolescents with sickle
      cell trait and other sickle hemoglobinopathies, and is refractory to targeted and
      antiangiogenic therapies used in patients with clear-cell renal cell carcinoma.
      Platinum-based cytotoxic chemotherapy is the mainstay for RMC treatment. On the
      basis of recent advances in the diagnosis, management, and clinical trial
      development for RMC, a panel of experts met in October 2017 and developed updated
      consensus recommendations to inform clinicians, researchers, and patients.
      Because RMC often aggressively recurs while patients are still recovering from
      nephrectomy, upfront chemotherapy should be considered for most patients,
      including those with localized disease. After safety and dosing information has
      been established in adults, phase II and III trials enrolling patients with RMC
      should allow patients aged 12 years and older to be accrued. Patients with the
      very rare unclassified renal cell carcinoma with medullary phenotype variant
      should be included in RMC trials. Medical providers should be aware that RMC can
      afflict subjects of all races, and not only those of African descent, and that
      the presence of sickle cell trait, or of other sickle hemoglobinopathies, can
      affect drug responses and toxicity.

PMID- 30287226
TI  - A standardized approach to the evaluation of antivirals against DNA viruses:
      Orthopox-, adeno-, and herpesviruses.
AB  - The search for new compounds with a broad spectrum of antiviral activity is
      important and requires the evaluation of many compounds against several distinct
      viruses. Researchers attempting to develop new antiviral therapies for DNA virus
      infections currently use a variety of cell lines, assay conditions and
      measurement methods to determine in vitro drug efficacy, making it difficult to
      compare results from within the same laboratory as well as between laboratories.
      In this paper we describe a common assay platform designed to facilitate the
      parallel evaluation of antiviral activity against herpes simplex virus type 1,
      herpes simplex virus type 2, varicella-zoster virus, cytomegalovirus, vaccinia
      virus, cowpox virus, and adenovirus. The automated assays utilize monolayers of
      primary human foreskin fibroblast cells in 384-well plates as a common cell
      substrate and cytopathic effects and cytotoxicity are quantified with CellTiter
      Glo. Data presented demonstrate that each of the assays is highly robust and
      yields data that are comparable to those from other traditional assays, such as
      plaque reduction assays. The assays proved to be both accurate and robust and
      afford an in depth assessment of antiviral activity against the diverse class of
      viruses with very small quantities of test compounds. In an accompanying paper,
      we present a standardized approach to evaluating antivirals against lymphotropic
      herpesviruses and polyomaviruses and together these studies revealed new
      activities for reference compounds. This approach has the potential to accelerate
      the development of broad spectrum therapies for the DNA viruses.

PMID- 30287227
TI  - A standardized approach to the evaluation of antivirals against DNA viruses:
      Polyomaviruses and lymphotropic herpesviruses.
AB  - The search for new compounds with a broad spectrum of antiviral activity is
      important and requires the evaluation of many compounds against several distinct
      viruses. Researchers attempting to develop new antiviral therapies for DNA virus
      infections currently use a variety of cell lines, assay conditions and
      measurement methods to determine in vitro drug efficacy, making it difficult to
      compare results from within the same laboratory as well as between laboratories.
      In this paper, we describe the assessment of antiviral activity of a set of
      nucleoside analogs against BK polyomavirus, JC polyomavirus, Epstein-Barr virus,
      human herpesvirus 6B, and human herpesvirus 8 in an automated 384-well format and
      utilize qPCR assays to measure the accumulation of viral DNA. In an accompanying
      paper, we present a standardized approach to evaluating antivirals against
      additional herpesviruses, orthopoxviruses, and adenovirus. Together, they reveal
      new activities for reference compounds and help to define the spectrum of
      antiviral activity for a set of nucleoside analogs against a set of 12 DNA
      viruses that infect humans including representative human herpesviruses,
      orthopoxviruses, adenoviruses, and polyomaviruses. This analysis helps provide
      perspective on combinations of agents that would help provide broad coverage of
      significant pathogens in immunocompromised patients as well as against emerging
      infections.

PMID- 30287228
TI  - Implementation of national screening guidelines for gestational diabetes: A
      national survey of maternity units in England.
AB  - AIMS: To describe national implementation of gestational diabetes (GDM) risk
      factor based screening guidelines, and barriers to implementation relating to
      maternal body mass index (BMI). METHODS: National online survey of NHS Trusts
      offering maternity services in England. A questionnaire was emailed to clinical
      staff involved in care of pregnant women assessing compliance with NICE
      guidelines for risk-factor based screening, BMI thresholds for offering OGTT and
      barriers to offering OGTT to women with BMI >= 30 kg/m2. RESULTS: Health
      professionals from 113 (84%) of NHS Trusts in England responded to the survey.
      Most Trusts (81%) offered OGTT at 26-28 weeks gestation to women with selected
      risk factors for GDM. However, almost 40% of Trusts were not fully compliant with
      NICE screening criteria for all risk factors, mainly due to not offering OGTT to
      women with previous GDM (25% of Trusts), BMI >= 30 kg/m2 or ethnic minority
      groups (22% of Trusts). The main barriers to compliance with the BMI threshold
      were lack of capacity, resource and funding given the high prevalence of maternal
      obesity. Forty one percent of Trusts used diagnostic thresholds for GDM which
      differed from NICE recommendations. CONCLUSIONS: Additional resources are
      required for NHS Trusts to fully implement and sustain risk-factor screening,
      especially for women with previous GDM, BMI >= 30 kg/m2 and ethnic minority
      groups.

PMID- 30287229
TI  - Sex- and age-related differences of metabolic parameters in impaired glucose
      metabolism and type 2 diabetes compared to normal glucose tolerance.
AB  - AIMS: This study analysed potential sex differences in glucose metabolism of
      European subjects with different degrees of glucose tolerance impairment.
      METHODS: Subjects with impaired glucose metabolism, IGM (n = 735), or type 2
      diabetes, T2DM (n = 415), were compared to subjects with normal glucose
      tolerance, NGT (n = 422), with similar BMI. For both males (M) and females (F),
      50 years threshold was used for estimation of menopausal/andropausal state.
      Subjects underwent 75-g OGTT for measurements of insulin sensitivity (OGIS), beta
      cell function (insulinogenic index, IGIC), and overall metabolic condition,
      disposition index (DI). RESULTS: In IGM, OGIS did not change with age in both
      sexes, whereas marked reduction of IGIC was seen in F (p = 0.0003). In T2DM,
      again OGIS did not change with age, but M >= 50 yrs had reduced IGIC and DI (p <
      0.002) compared to M < 50 yrs. CONCLUSIONS: IGM did not reveal relevant changes
      of insulin resistance with age, but early phase insulin release deteriorated,
      with higher change in women. T2DM men featured age-related deterioration of
      glucose metabolism. In women, sex advantage seen in NGT vanished in T2DM, since
      glucose metabolism was overall not different than in men, both young and elderly.

PMID- 30287230
TI  - Impact of sertraline on weight, waist circumference and glycemic control: A
      prospective clinical trial on depressive diabetic type 2 patients.
AB  - AIM: Depression is prevalent in patients with type 2 diabetes. It may have a
      negative impact on the management of diabetes mellitus and could affect weight.
      The main aim of the investigation was to evaluate the effect of antidepressant
      treatment (sertraline) on anthropometric variables and glycemic control in
      depressed type 2 diabetic patients. METHODS: Thirty three type 2 diabetic
      outpatients depressed received open-label sertraline therapy for up to 12 weeks.
      Clinical outcome measures included the 17-item Hamilton depression rating.
      Changes in the anthropometrics variables were evaluated by measuring weight,
      waist circumference and by calculating body mass index at three, six and 12 weeks
      of treatment. In addition, fasting, postprandial plasma glucose level,
      glycosylated hemoglobin-A 1C measures, lipid and renal profile were obtained
      before and during sertraline therapy. RESULTS: Weight decreased significantly (
      2kg; p=0.000) and body mass index decreased from 30.41kg/m2 to 29.6kg/m2
      (p=0.000). Patients lost on average seven centimeters in waist circumference
      (p=0.000). We also observed a modest, non-significant reduction in fasting,
      postprandial and glycosylated hemoglobin. We observed a significant reduction in
      mean score according to the Hamilton depression scale (p=0.000) CONCLUSION: Our
      study results suggested that sertraline produced a benefic effect on weight, body
      mass index and waist circumference at 12-week follow up.

PMID- 30287231
TI  - Strategy for performing treponemal tests in reverse-sequence algorithms of
      syphilis diagnosis.
AB  - OBJECTIVES: In South Korea, automated T. pallidum Latex Agglutination (TPLA)
      based on turbidoimmunoassays and immunochromatographic assay (ICA) are widely
      used for syphilis diagnosis. However, there is sparse data on the validation of
      these assays in the reverse-sequence algorithm setting. METHODS: We assessed 551
      specimens submitted for syphilis testing. We compared varying reverse-sequence
      algorithms using combinations of the Cobas Syphilis EIA (Roche Diagnostics,
      Mannheim, Germany), Mediace TPLA (Sekisui Medical Co., Tokyo, Japan), TPPA
      (Fujirebio Inc., Tokyo, Japan), and SD Bioline ICA (Standard Diagnostic, Yongin,
      Korea). We also evaluated modified algorithms incorporating a cut off of high
      specificity for EIA and TPLA using receiver operating characteristic curves.
      RESULTS: The agreement was almost perfect between EIA and TPLA (Kappa, 0.953) and
      strong between TPPA and ICA (Kappa, 0.887). Among TPPA positive and ICA negative
      specimens, 67% of the specimens were from individuals with syphilis histories.
      Compared to EIA/RPR/TPPA, the agreement with EIA/RPR/ICA, TPLA/RPR/TPPA and
      TPLA/RPR/ICA were almost perfect (Kappa, 0.930, 0.995 and 0.914, respectively).
      When a cut off of 95% specificity was applied, the number of TPPA tests could be
      reduced by 44% and 40% in EIA and TPLA, respectively. CONCLUSIONS: TPLA showed
      almost perfect agreement with EIA and that it could be used in the site of EIA in
      a reverse sequence algorithm. ICA showed a lower detection rate than TPPA as a
      2nd treponemal test and should be used with caution. With cut offs of higher
      specificity, more efficient reverse-sequence algorithms can be made possible.

PMID- 30287232
TI  - Two observational studies examining the effect of a social norm and a health
      message on the purchase of vegetables in student canteen settings.
AB  - There is some evidence from laboratory-based studies that descriptive social-norm
      messages are associated with increased consumption of vegetables, but evidence of
      their effectiveness in real-world settings is limited. In two observational field
      studies taking an ecological approach, a vegetable-related social norm (e.g. "Did
      you know that most students here choose to eat vegetables with their meal?"), and
      a health message (e.g. "Did you know that students who choose to eat vegetables
      have a lower risk of heart disease?") were displayed in two different student
      canteens. Purchases were observed during three stages: baseline, intervention
      (when the posters were displayed) and immediate post-intervention (when the
      posters had been removed). Study 1 (n = 7598) observed the purchase of meals
      containing a portion of vegetables and Study 2 (n = 4052) observed the purchase
      of side portions of vegetables. In Study 1, relative to baseline, the social
      norms intervention was associated with an increase in purchases of vegetables
      (from 63% to 68% of meals; OR = 1.24, CI = 1.03-1.49), which was sustained post
      intervention (67% of meals; OR = 0.96, CI = 0.80-1.15). There was no effect of
      the health message (75% of meals at baseline, and 74% during the intervention; OR
      = 0.98, CI = 0.83-1.15). In Study 2, relative to baseline, there was an effect of
      both the social norm (22.9% of meals at baseline, rising to 32.5% during the
      intervention; OR = 1.62, CI = 1.27-2.05) and health message (rising from 43.8% at
      baseline to 52.8%; OR = 0.59, CI = 0.46-0.75). The increase was not sustained
      post-intervention for the social norm intervention (22.1%; OR = 0.59, CI = 0.46
      0.75), but was sustained for the health intervention (48.1%; OR = 0.83, CI = 0.67
      1.02). These results support further testing of the effectiveness of such
      messages in encouraging healthier eating and indicate the need for larger-scale
      testing at multiple sites using a randomised-controlled design.

PMID- 30287233
TI  - Effect of efferocytosis of apoptotic mesenchymal stem cells (MSCs) on C57BL/6
      peritoneal macrophages function.
AB  - Phagocytic clearance of apoptotic cells (Efferocytosis) could affect the
      polarization of macrophages and promote M2 anti-inflammatory and regulatory
      phenotype and function. Here we tested the hypothesis that efferocytosis of
      apoptotic Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) promotes macrophage M2
      polarization. In this study, Macrophages were incubated with apoptotic MSCs and
      after 48 h interleukin-10 (IL-10), transforming growth factor-alpha (TNFalpha),
      and nitric oxide (NO) production were measured. Furthermore, phagocytosis ability
      and arginase activity were analyzed. The results showed that apoptotic MSCs could
      reduce TNFalpha and NO production, and increase IL-10 levels. Moreover, arginase
      activity and phagocytosis ability were also increased in tested macrophages
      compared to controls. In Conclusion efferocytosis of AD-MSCs can alter the
      macrophages phenotype toward regulatory and anti-inflammatory phenotype.

PMID- 30287225
TI  - Sphingolipids in neurodegeneration (with focus on ceramide and S1P).
AB  - For many decades, research on sphingolipids associated with neurodegenerative
      disease focused on alterations in glycosphingolipids, particularly
      glycosylceramides (cerebrosides), sulfatides, and gangliosides. This seemed quite
      natural since many of these glycolipids are constituents of myelin and
      accumulated in lipid storage diseases (sphingolipidoses) resulting from enzyme
      deficiencies in glycolipid metabolism. With the advent of recognizing ceramide
      and its derivative, sphingosine-1-phosphate (S1P), as key players in lipid cell
      signaling and regulation of cell death and survival, research focus shifted
      toward these two sphingolipids. Ceramide and S1P are invoked in a plethora of
      cell biological processes participating in neurodegeneration such as ER stress,
      autophagy, dysregulation of protein and lipid transport, exosome secretion and
      neurotoxic protein spreading, neuroinflammation, and mitochondrial dysfunction.
      Hence, it is timely to discuss various functions of ceramide and S1P in
      neurodegenerative disease and to define sphingolipid metabolism and cell
      signaling pathways as potential targets for therapy.

PMID- 30287234
TI  - Phloretin cytoprotection and toxicity.
AB  - Phloretin (Phl) is a dihydrochalcone flavonoid with significant cytoprotective
      properties; e.g., free radical trapping, electrophile scavenging. Based on this,
      it has been suggested that Phl might be useful in the treatment of pathogenic
      processes and prevention of drug toxicities. Therefore, we determined the ability
      of Phl to provide route- and dose-dependent hepatoprotection in a mouse model of
      acetaminophen (APAP) overdose. Intraperitoneal (i.p.) administration of Phl
      produced a bimodal effect; i.e., the highest dose (2.40 mmol/kg) did not prevent
      APAP-induced lethality, whereas lower doses (0.2-0.4 mmol/kg) afforded modest
      hepatoprotection. When given alone, the highest i.p. Phl dose was lethal within
      24 h, whereas the lower doses were not toxic. Oral Phl (0.40-2.40 mmol/kg) did
      not prevent APAP-induced hepatotoxicity. The highest oral dose given alone (2.4
      mmol/kg) produced 64% lethality, whereas lower doses were not lethal. This
      toxicity profile was reflected in a study using APAP-exposed isolated mouse
      hepatocytes, which showed that the Phl pharmacophores, 1,3,5
      trihydroxyacetophenone (PG) and 2',4',6'-trihydroxyacetophenone (THA) where
      protective. Corroborative cell free studies showed that polyphenol protectants
      prevented glutathione loss mediated by the APAP metabolite, N-acetyl-p
      benzoquinone imine (NAPQI). Thus, in spite of possessing cytoprotective
      attributes, Phl was generally toxic in our APAP models. These and earlier
      findings suggest that Phl is not a candidate for drug design. In contrast, we
      have found that the enol-forming pharmacophores, THA and PG, are potential
      platforms for pharmacotherapeutic development.

PMID- 30287235
TI  - The relationship between ferritin levels and oxidative stress parameters in serum
      of beta-thalassemia major patients.

PMID- 30287236
TI  - Active site arginine controls the stereochemistry of hydride transfer in
      cyclohexanone monooxygenase.
AB  - Cyclohexanone monooxygenase (CHMO) uses NADPH and O2 to insert oxygen into an
      array of (a)cyclic ketones to form esters or lactones. Herein, the role of two
      conserved active site residues (R327 and D57) in controlling the binding mode of
      NADP(H) was investigated. Wild type CHMO elicits a kinetic isotope effect (KIE)
      of 4.7 +/- 0.1 and 1.1 +/- 0.1 with 4(R)-[4-2H]NADPH and 4(S)-[4-2H]NADPH,
      respectively, consistent with transfer of the proR hydrogen to FAD. Strikingly,
      the R327K variant appears to lack stereospecificity for hydride transfer as a KIE
      of 1.5 +/- 0.1 and 2.5 +/- 0.1 was observed for the proR and proS deuterated
      forms of NADPH. 1H NMR of the NADP+ products confirmed that the R327K variant
      abstracts either the proR or proS hydrogen from NADPH. While the D57A variant
      retained stereospecificity for the proR hydrogen, this substitution resulted in
      slow decomposition of the C4a-peroxyflavin intermediate in the presence of
      cyclohexanone. Based on published structures of a related flavin monooxygenase,
      we suggest that elimination of the hydrogen bond between D57 and R327 in the D57A
      variant causes R327 to adopt a substrate-induced conformation that slows
      substrate access to the active site, thereby prolonging the lifetime of the C4a
      peroxyflavin intermediate.

PMID- 30287238
TI  - Optimal Therapy for Unstable Pulmonary Embolism.
AB  - There are no randomized controlled trials of thrombolytic therapy, pulmonary
      embolectomy, or inferior vena cava (IVC) filters in patients with unstable
      pulmonary embolism (those in shock or on ventilator support). Yet, there are many
      investigations of these treatments based on retrospective cohort studies using
      administrative data from large government and commercial databases. Extensive
      data from these cohort studies showed that thrombolytic therapy resulted in the
      lowest in-hospital all-cause mortality. The results of thrombolytic therapy were
      greatly improved if IVC filters were added. In fact, IVC filters decreased in
      hospital all-cause mortality with anticoagulants alone or pulmonary embolectomy
      as well as thrombolytic therapy in adults of all ages with unstable pulmonary
      embolism. The IVC filters reduced mortality only if inserted on the day of
      admission or the next day, while the patients were unstable and in a fragile
      condition. We conclude that the best treatment for patients with unstable
      pulmonary embolism is thrombolytic therapy combined with an IVC filter inserted
      during the period of fragility, while the patient is unstable, and this treatment
      is indicated in all unstable patients irrespective of age.

PMID- 30287237
TI  - Piperine, an alkaloid inhibiting the super-relaxed state of myosin, binds to the
      myosin regulatory light chain.
AB  - Piperine, an alkaloid from black pepper, was found to inhibit the super-relaxed
      state (SRX) of myosin in fast-twitch skeletal muscle fibers. In this work we
      report that the piperine molecule binds heavy meromyosin (HMM), whereas it does
      not interact with the regulatory light chain (RLC)-free subfragment-1 (S1) or
      with control proteins from the same muscle molecular machinery, G-actin and
      tropomyosin. To further narrow down the location of piperine binding, we studied
      interactions between piperine and a fragment of skeletal myosin consisting of the
      full-length RLC and a fragment of the heavy chain (HCF). The sequence of HCF was
      designed to bind RLC and to dimerize via formation of a stable coiled coil, thus
      producing a well-folded isolated fragment of the myosin neck. Both chains were co
      expressed in Escherichia coli, the RLC/HCF complex was purified and tested for
      stability, composition and binding to piperine. RLC and HCF chains formed a
      stable heterotetrameric complex (RLC/HCF)2 which was found to bind piperine. The
      piperine molecule was also found to bind isolated RLC. Piperine binding to RLC in
      (RLC/HCF)2 altered the compactness of the complex, suggesting that the mechanism
      of SRX inhibition by piperine is based on changing conformation of the myosin.

PMID- 30287239
TI  - Characterization of Electrocardiographic Findings in Young Students.
AB  - INTRODUCTION AND OBJECTIVES: The resting 12-lead electrocardiogram (ECG) has been
      used in the evaluation of young asymptomatic individuals to detect pre-existing
      heart disease, but systematic ECG use is controversial and there are no data on
      this population in our environment. We aimed to determine the prevalence and
      spectrum of electrocardiographic findings in a population of secondary school
      students. METHODS: We conducted an observational, cross-sectional study of
      resting ECG findings in all 13 to 14-year-old secondary school students in a
      region of the province of Gerona between 2009 and 2017. ECG findings were
      classified into 3 groups according to the modified criteria of Corrado et al.:
      normal ECG findings, ECG findings suggestive of adaptive changes, and pathologic
      findings. Students with pathologic ECG findings were referred to a tertiary
      hospital, and complementary tests were performed according to a pre-established
      protocol. RESULTS: A total of 1911 ECGs were obtained, with a participation rate
      of 79% of all high school students. In all, 1321 students (69%) had a normal ECG,
      554 (29%) showed ECG findings suggestive of adaptive changes, and 36 (2%) had
      pathologic ECG findings. Among the group with pathologic findings, 5 (14%) had
      cardiovascular disease. The prevalence of heart disease in this group of
      asymptomatic secondary school students was 0.3%. CONCLUSIONS: One third of the
      students had ECG findings that were mostly suggestive of physiological
      adaptation. One seventh of the students with pathologic ECG findings had pre
      existing heart disease, although the overall prevalence of pre-existing heart
      disease was low.

PMID- 30287241
TI  - Percutaneous Closure of a Large Paravalvular Prosthetic Aortic Leak.

PMID- 30287240
TI  - Adherence to an Energy-restricted Mediterranean Diet Score and Prevalence of
      Cardiovascular Risk Factors in the PREDIMED-Plus: A Cross-sectional Study.
AB  - INTRODUCTION AND OBJECTIVES: The cardiovascular benefits of the Mediterranean
      diet have usually been assessed under assumptions of ad libitum total energy
      intake (ie, no energy restriction). In the recently launched PREDIMED-Plus, we
      conducted exploratory analyses to study the baseline associations between
      adherence to an energy-restricted Mediterranean diet (MedDiet) and the prevalence
      of cardiovascular risk factors (CVRF). METHODS: Cross-sectional assessment of all
      PREDIMED-Plus participants (6874 older adults with overweight/obesity and
      metabolic syndrome) at baseline. The participants were assessed by their usual
      primary care physicians to ascertain the prevalence of 4 CVRF (hypertension,
      obesity, diabetes, and dyslipidemia). A 17-point PREDIMED-Plus score was used to
      measure adherence to the MedDiet. Multivariable models were fitted to estimate
      differences in means and prevalence ratios for individual and clustered CVRF.
      RESULTS: Better adherence to a MedDiet pattern was significantly associated with
      lower average triglyceride levels, body mass index, and waist circumference.
      Compared with low adherence (<= 7 points in the 17-point score), better adherence
      to the MedDiet (11-17 points) showed inverse associations with hypertension
      (prevalence ratio=0.97; 95%CI, 0.94-1.00) and obesity (prevalence ratio=0.96;
      95%CI, 0.92-1.00), but positive associations with diabetes (prevalence
      ratio=1.19; 95%CI, 1.07-1.32). Compared with the lowest third of adherence, women
      in the upper third showed a significantly lower prevalence of the clustering of 3
      or more CVRF (prevalence ratio=0.91; 95%CI, 0.83-0.98). CONCLUSIONS: Among
      participants at high cardiovascular risk, better adherence to a MedDiet showed
      significant inverse associations with CVRF among women, and improved lipid
      profiles and adiposity measures. This trial was registered in 2014 at the
      International Standard Randomized Controlled Trial Registry (ISRCTN89898870).

PMID- 30287242
TI  - The transcriptomic expression of pattern recognition receptors: Insight into
      molecular recognition of various invading pathogens in Oyster Crassostrea gigas.
AB  - Pattern recognition receptors (PRRs) are essential in recognizing specific
      pathogen-associated molecular patterns (PAMPs) on microbes and triggering
      responses to eliminate the invading pathogens. Previous genomic studies have
      revealed a great number of PRR genes in the Pacific oyster Crassostrea gigas, a
      sessile and filter-feeder marine bivalve belonging to the phylum Mollusca. On the
      survey of PRRs in the assembly oyster reference genome version 9, a total of 1084
      PRRs were identified, which were composed of at least 12 gene families. Some of
      the gene families were significantly expanded, including C-type lectins (CTLs),
      fibrinogen-related proteins (FREPs), scavenger receptor cysteine-rich repeat
      protein (SRCRs), leucine-rich repeat (LRR)-only proteins (LRRops), and especially
      C1q domain-containing proteins (C1qDCs). The transcriptomic profiles of these
      abundant PRRs in response to PAMP treatments were investigated by RNA-Seq using
      the SOLiD EZ BeadTM system. Compared to the control library, there were 6,655,
      7,273, 7,593, 6,830, 6687 and 8250 differentially expressed genes in the
      haemocytes of oysters in response to lipopolysaccharide (LPS) stimulation for 6
      h, 12 h and 24 h, and peptidoglycan (PGN), glucan (GLU) and poly I:C (IC)
      stimulation for 12 h, respectively. After stimulation for 12 h, there were 134,
      97, 114 and 159 genes up-regulated in the LPS, PGN, GLU and IC library,
      respectively. Most of the gene families involved in immune response towards PAMPs
      were C1qDCs, CTLs and FREPs, while only a few members of LRR and immunoglobin
      containing proteins (LRRIGs), retinoic acid-inducible gene I [RIG-I]-like
      receptors (RLRs) and Toll like receptors (TLRs) were up-regulated. After LPS
      stimulation, the expression level of 258 non-redundant PRR genes in oyster
      haemocytes increased significantly with different expression pattern, and most of
      them were C1qDCs, CTLs, LRRops and FREPs. The transcriptomic analyses indicated
      that there was a dynamic and orchestrated specific expression regulation of
      numerous PRR genes in response to pathogen invasion. The expanded PRR gene family
      members were differentiated with more specific functional responses to certain
      PAMPs rather than the versatile ones. Based on the different expression pattern
      during the LPS stimulation, the oyster PRRs could be assigned into three
      consecutive steps in the response against pathogen invading. All the results
      would provide useful information for future studies of oyster PRRs and deep
      insight into the researches on invertebrate innate immunity.

PMID- 30287244
TI  - Characterization of an RNase with two catalytic centers. Human RNase6 catalytic
      and phosphate-binding site arrangement favors the endonuclease cleavage of
      polymeric substrates.
AB  - BACKGROUND: Human RNase6 is a small cationic antimicrobial protein that belongs
      to the vertebrate RNaseA superfamily. All members share a common catalytic
      mechanism, which involves a conserved catalytic triad, constituted by two
      histidines and a lysine (His15/His122/Lys38 in RNase6 corresponding to
      His12/His119/Lys41 in RNaseA). Recently, our first crystal structure of human
      RNase6 identified an additional His pair (His36/His39) and suggested the presence
      of a secondary active site. METHODS: In this work we have explored RNase6 and
      RNaseA subsite architecture by X-ray crystallography, site-directed mutagenesis
      and kinetic characterization. RESULTS: The analysis of two novel crystal
      structures of RNase6 in complex with phosphate anions at atomic resolution
      locates a total of nine binding sites and reveals the contribution of Lys87 to
      phosphate-binding at the secondary active center. Contribution of the second
      catalytic triad residues to the enzyme activity is confirmed by mutagenesis.
      RNase6 catalytic site architecture has been compared with an RNaseA engineered
      variant where a phosphate-binding subsite is converted into a secondary catalytic
      center (RNaseA-K7H/R10H). CONCLUSIONS: We have identified the residues that
      participate in RNase6 second catalytic triad (His36/His39/Lys87) and secondary
      phosphate-binding sites. To note, residues His39 and Lys87 are unique within
      higher primates. The RNaseA/RNase6 side-by-side comparison correlates the
      presence of a dual active site in RNase6 with a favored endonuclease-type
      cleavage pattern. GENERAL SIGNIFICANCE: An RNase dual catalytic and extended
      binding site arrangement facilitates the cleavage of polymeric substrates. This
      is the first report of the presence of two catalytic centers in a single monomer
      within the RNaseA superfamily.

PMID- 30287243
TI  - ALDH1-positive intratumoral stromal cells indicate differentiated epithelial-like
      phenotype and good prognosis in prostate cancer.
AB  - Aldehyde dehydrogenase 1 (ALDH1) characterizes tumor-initiating cells in solid
      tumors; however, little is known about its expression in intratumoral stromal
      cells. Herein, we aimed to dissect its potential dual relevance in prostate
      cancer (PCa). ALDH1 expression was evaluated immunohistochemically in tumor and
      stromal cells in primary PCa and metastases. It was correlated to clinico
      pathologic parameters, patients' outcome, and selected proteins (CK5/6, CK14,
      CK8/18, CK19, EpCAM, Ki-67, E-cadherin, N-cadherin, and vimentin). ALDH1 protein
      was detected in tumor and stromal cells in 16% and 67% of 348 primary PCa,
      respectively. Tumor cell ALDH1 expression was associated with advanced T stage (P
      = 0.009), higher Gleason score (P = 0.016), shorter time to biochemical
      recurrence (TBR P = 0.010) and CK14 expression (P = 0.023). Stromal cell ALDH1
      expression correlated to lower T stage (P = 0.008) and Gleason score (P = 0.016),
      N0 stage (P = 0.017), and longer TBR (P = 0.017). It occurred to be an
      independent predictor of good prognosis in the subgroup of d'Amico high-risk
      patients (multivariate analysis, P = 0.050). ALDH1-positive stromal cells were
      found in tumors characterized frequently by CK8/18 (P = 0.033) or EpCAM
      expression (P < 0.001) and rarely by epithelial-mesenchymal transition defined as
      CK8/18(-)vimentin(+) phenotype (P = 0.003). ALDH1-positive tumor and stromal
      cells were detected in 33% and 41% of hormone naive lymph node metastases (n =
      63), 52% and 24% of castration resistant bone metastases, as well as 89% and 28%
      of castration resistant visceral metastases (n = 21), respectively. We have
      determined that contrary to tumor cell ALDH1, the presence of stromal ALDH1 is
      associated with epithelial phenotype of primary PCa, improved clinical outcome,
      and is less frequent in PCa metastases.

PMID- 30287245
TI  - Audiovisual multisensory integration in individuals with autism spectrum
      disorder: A systematic review and meta-analysis.
AB  - An ever-growing literature has aimed to determine how individuals with autism
      spectrum disorder (ASD) differ from their typically developing (TD) peers on
      measures of multisensory integration (MSI) and to ascertain the degree to which
      differences in MSI are associated with the broad range of symptoms associated
      with ASD. Findings, however, have been highly variable across the studies carried
      out to date. The present work systematically reviews and quantitatively
      synthesizes the large literature on audiovisual MSI in individuals with ASD to
      evaluate the cumulative evidence for (a) group differences between individuals
      with ASD and TD peers, (b) correlations between MSI and autism symptoms in
      individuals with ASD and (c) study level factors that may moderate findings
      (i.e., explain differential effects) observed across studies. To identify
      eligible studies, a comprehensive search strategy was employed using the ProQuest
      search engine, PubMed database, forwards and backwards citation searches, direct
      author contact, and hand-searching of select conference proceedings. A
      significant between-group difference in MSI was evident in the literature, with
      individuals with ASD demonstrating worse audiovisual integration on average
      across studies compared to TD controls. This effect was moderated by mean
      participant age, such that between-group differences were more pronounced in
      younger samples. The mean correlation between MSI and autism and related
      symptomatology was also significant, indicating that increased audiovisual
      integration in individuals with ASD is associated with better
      language/communication abilities and/or reduced autism symptom severity in the
      extant literature. This effect was moderated by whether the stimuli were
      linguistic versus non-linguistic in nature, such that correlation magnitudes
      tended to be significantly greater when linguistic stimuli were utilized in the
      measure of MSI. Limitations and future directions for primary and meta-analytic
      research are discussed.

PMID- 30287246
TI  - Counseling and referrals for women with unplanned pregnancies at publicly funded
      family planning organizations in Texas.
AB  - OBJECTIVES: To compare pregnancy options counseling and referral practices at
      state- and Title X-funded family planning organizations in Texas after
      enforcement of a policy restricting abortion referrals for providers
      participating in state-funded programs, which differed from Title X guidelines to
      provide referrals for services upon request. STUDY DESIGN: Between November 2014
      and February 2015, we conducted in-depth interviews with administrators at
      publicly funded family planning organizations in Texas about how they integrated
      primary care and family planning services, including pregnancy options counseling
      and referrals for unplanned pregnancies. We conducted a thematic analysis of
      transcripts related to organizations' pregnancy options counseling and referral
      practices, and compared themes across organizations that did and did not receive
      Title X funding. RESULTS: Of the 37 organizations with transcript segments on
      options counseling and referrals, 15 received Title X and 22 relied on state
      funding only. All Title X-funded organizations but only nine state-funded
      organizations reported offering pregnancy options counseling. Respondents at
      state-only-funded organizations often described directing pregnant women
      exclusively to prenatal care. Regardless of funding source, most organizations
      provided women a list of agencies offering abortion, adoption and prenatal care.
      However, some respondents expressed concern that providing other information
      about abortion would threaten their state funding. In contrast, respondents
      indicated staff would make appointments for prenatal care, assist with Medicaid
      applications and, in some instances, directly connect women with adoption-related
      services. CONCLUSIONS: Pregnancy options counseling varied by organizations'
      funding guidelines. Additionally, abortion referrals were less common than
      referrals for other pregnancy-related care. IMPLICATIONS: Programmatic guidelines
      restricting information on abortion counseling and referrals may adversely affect
      care for pregnant women at publicly funded family planning organizations.

PMID- 30287247
TI  - The Clinical Significance of Cerebral Microbleeds in Infective Endocarditis
      Patients.
AB  - We assessed the clinical features of cerebral microbleeds (CMBs) and their
      association with clinical outcomes in active infective endocarditis patients.
      From January 2009 to June 2015, 132 active IE patients diagnosed per the modified
      Duke's criteria were retrospectively reviewed. Brain magnetic resonance imaging
      was performed in 102 patients, and 74 patients whose image data were available to
      assess CMBs were enrolled. CMBs were defined as hypointense lesion <10 mm in
      diameter, seen on T2* or susceptibility-weighted imaging. Forty patients had CMB
      and 34 did not. Patients with CMB were older, and the proportion of prior
      antiplatelet therapy, staphylococcal infection, and prosthetic valve endocarditis
      were higher than in patients without CMB. Surgery was performed in 25 (63%)
      patients with CMB and 24 (71%) patients without CMB. There was no significant
      difference in the de novo stroke incidence postoperatively (16% vs 17%, P =
      0.95). Although all-cause mortality rate tended to be higher in patients with
      CMB, there were no significant differences in the in-hospital mortality rate and
      estimated 1-year major adverse event rate between the 2 groups (13% vs 12%, P =
      0.92; 20% vs 19%, P = 0.35). Cox regression analysis adjusting age and operative
      risk did not show that CMB was a significant risk factor for all-cause death and
      major adverse event. Patients with CMB were older than those without, and
      microbleeds were associated with antiplatelet therapy, staphylococcal infection,
      and prosthetic valve endocarditis. However, the mid-term clinical outcomes of
      patients with CMB and those without were comparable.

PMID- 30287248
TI  - Predictive value of plasma matrix metalloproteinase-9 concentrations for
      spontaneous haemorrhagic transformation in patients with acute ischaemic stroke:
      A cohort study in Chinese patients.
AB  - Whether matrix metalloproteinase 9 (MMP-9) concentrations in plasma predict risk
      of spontaneous haemorrhagic transformation (sHT) in acute ischaemic stroke is
      unclear. From 1 March 2003 to 27 February 2006, patients with acute ischaemic
      stroke admitted to West China Hospital within 24 h of onset and healthy controls
      were enrolled and blood samples obtained. Plasma MMP-9 concentrations were
      determined using enzyme-linked immunosorbent assay, and sHT was diagnosed based
      on brain computed tomography or magnetic resonance performed 3-14 d after stroke
      onset. MMP-9 concentrations were compared for sHT patients, non-sHT patients and
      healthy controls. The threshold concentration for predicting sHT was determined
      using receiver operating characteristic analysis and the association between MMP
      9 concentration and sHT was tested. One hundred and sixty-eight stroke patients
      and 40 healthy controls were included. Spontaneous HT occurred in 17.3% (29/168)
      of stroke patients and median plasma MMP-9 concentration in the sHT subgroup
      [244.3 ng/mL; interquartile range (IQR), 190.6-431.4] was significantly higher
      than in the non-sHT subgroup (110.0 ng/mL; IQR, 54.4-172.2) as well as in healthy
      controls (63.3 ng/mL; IQR 37.9-84.9) (both P < 0.001). We identified 181.7 ng/mL
      as the threshold MMP-9 concentration, for which the positive predictive value was
      48% and the negative predictive value was 96%. After controlling for potential
      confounding factors, MMP-9 concentration >181.7 ng/mL was an independent
      predictor of sHT (odds ratio 18.8, 95% confidence interval 6.0-58.5, P < 0.001).
      Plasma MMP-9 concentration >181.7 ng/mL within 24 h after stroke onset
      independently predicts sHT in patients with ischaemic stroke.

PMID- 30287249
TI  - Hemangioblastomatosis-associated negative-pressure hydrocephalus managed with
      improvised shunt.
AB  - Low-pressure hydrocephalus (LPH) is a rare clinical diagnosis, characterized by
      neurologic decline and ventriculomegaly that persists despite normal to low
      intracranial pressure. LPH is typically managed by negative-pressure drainage via
      ventriculostomy, followed by low-resistance shunt insertion. We present the case
      of a middle-aged man with a history of hemangioblastomatosis who had spontaneous
      subarachnoid hemorrhage. He was treated with a ventriculoperitoneal shunt and
      then underwent resection of a Meckel's cave hemangioblastoma and whole brain
      irradiation. One month later, he presented to us with worsening symptoms and
      hydrocephalus despite shunt interrogations and revisions revealing no
      malfunction. Ventriculostomy drainage at negative-pressure was required for
      resolution of symptoms and ventriculomegaly, leading us to a diagnosis of LPH.
      This was successfully treated using an improvised ultra-low pressure valveless
      ventriculoperitoneal shunt, with maintained resolution of LPH for over one year.
      The system was created by ligating the distal slit valve end of a peritoneal
      catheter to prevent reflux and allow sub-zero pressure drainage by siphoning.

PMID- 30287250
TI  - Patterns of care and outcomes of postoperative radiation for low-grade gliomas in
      United States hospitals.
AB  - It is unclear whether there is a survival benefit with postoperative radiation
      for low-grade gliomas deemed to be high-risk. We sought to analyze patterns of
      care and outcomes of radiation use. We accessed the National Cancer Database to
      identify patients with WHO grade II oligodendroglioma or astrocytoma between 2010
      and 2012. Multivariable logistic regression was used to identify predictors of
      radiation use and multivariable Cox regression was used to identify covariables
      associated with differences in survival. There were 1952 patients included in
      this study, of which 518 (26.5%) received postoperative radiation. The majority
      had oligodendroglioma histology (n = 1121, 57.4%) compared to astrocytoma (n =
      831, 42.6%). There were 1626 patients who were either >=40 years old or underwent
      a subtotal resection ("high-risk"), and from these 495 (30.4%) received
      postoperative radiation. On multivariable logistic regression treatment at an
      academic facility (OR 0.72) was associated with a lower likelihood of receiving
      postoperative radiation. Astrocytoma histology (OR 2.08), age >=40 years (OR
      2.23), tumor size >=6 cm (OR 1.64), subtotal resection (OR 1.55), and
      chemotherapy use (OR 3.93) were associated with an increased likelihood of
      postoperative radiation. On multivariable analysis, astrocytoma histology (HR
      3.49, p < 0.001) and receipt of radiation (HR 2.06, p < 0.001) were associated
      with worse overall survival. GTR (HR 0.51, p = 0.001) was associated with
      improved overall survival. Patients treated in United States hospitals are not
      routinely referred for postoperative radiation for high-risk, low-grade gliomas.
      Patients who received radiation did not do better than those who did not receive
      radiation.

PMID- 30287251
TI  - Corrigendum to "Reconstructive outcome of intraoperative cerebrospinal fluid leak
      after endoscopic endonasal surgery for tumors involving skull base" [J. Clin.
      Neurosci. 45 (2017) 227-231].

PMID- 30287252
TI  - Enhanced mortality in deltamethrin-resistant Aedes aegypti in Thailand using a
      piperonyl butoxide synergist.
AB  - Aedes aegypti is the primary vector of dengue viruses in Thailand. Control of
      this mosquito continues to rely heavily on use of insecticides in various forms
      and applications. The synergistic effect of piperonyl butoxide (PBO), combined
      with deltamethrin against eight populations of Ae. aegypti collected from
      different regions in Thailand is presented. The standard WHO adult contact
      bioassays found all populations with low to moderate levels of resistance to
      deltamethrin alone (using a 0.05% discriminating concentration), with final
      mortalities ranging from 15.6 to 70%, while a laboratory strain was fully
      susceptible (100% mortality). Pre-exposure of female mosquitoes to 4% PBO for 1
      h, followed immediately by exposure to deltamethrin for 1 h, significantly
      increased mortality in seven populations (64.8-98.1%) with the exception of
      mosquitoes derived from Lampang Province. The knockdown time (KDT) synergist
      ratios between deltamethrin only and PBO + deltamethrin ranged from 1.7 to 2.8
      for KDT50 and 1.9 to 4.0 for KDT95. Between deltamethrin alone and mosquitoes
      exposed to PBO + deltamethrin, all resistant populations produced significant
      differences (P < 0.05) in final 24-h mortality, except marginally for Lampang (P
      = 0.053). The synergistic effects of PBO with deltamethrin-resistant Ae. aegypti
      suggest a combination of this synergist with deltamethrin or other pyrethroid
      compounds can significantly enhance the effectiveness of these insecticides
      against pyrethroid-resistant Ae. aegypti found commonly in Thailand.

PMID- 30287253
TI  - Phyto-miRNA: A molecule with beneficial abilities for plant biotechnology.
AB  - The discovery of the phenomenon of gene silencing in 1990s opened new doors to
      biotechnology and plant breeding in order to supply food security. Food Security,
      as defined by FAO, it exists when all people, at all times, have economic access
      to safe, sufficient and nutritious food to meet their dietary needs and food
      preferences for a healthy and active life. Due to the need to ensure food
      security and also gene silencing potentials, research in this field began with
      astonishing speed and even it still continues. In this field, miRNA-associated
      gene silencing especially attracted the attention of scientists in order to
      decrypt the genes involved in process such as plant growth and development,
      metabolism, signal transduction, response against environmental stresses, nodule
      development in legumes and inducement male sterility. In addition, miRNA found a
      lot of applications in plant biotechnology like miRNA-based molecular markers and
      miRNA-based molecular breeding for plants improvement. Given to the growing
      importance of plant miRNAs (Phyto-miRNAs) in biotechnology and expansion of their
      applications in molecular breeding, it is necessary to review miRNA in an up-to
      date schema. In this study, it was presented both the necessary foundations of
      miRNAs and their important uses in plant sciences, such as molecular markers and
      metabolic engineering. As a result, we hope to expand the use of artificial
      miRNAs in plants engineering.

PMID- 30287254
TI  - Genomic alterations driving psoriasis pathogenesis.
AB  - Psoriasis is an immune mediated inflammatory skin disease with complex etiology
      involving interplay between environmental and genetic risk factors as disease
      initiating event. Enhanced understanding on genetic risk factors, differentially
      expressed genes, deregulated proteins and pathway-targeted therapeutics have
      established multiple axis of psoriasis pathogenesis. So far, loci in 424 genes
      are reported to be associated with psoriasis alongside copy number variations and
      epigenetic alterations. From clinical perspective, presence of specific genetic
      trigger(s) in individual psoriasis patient could aid in devising a personalized
      therapeutic strategy. Therefore, the review presents an updates on reported
      genomic alterations and their subsequent course of cutaneous inflammations that
      potentially drive to psoriasis.

PMID- 30287256
TI  - Dr. Kimishige Ishizaka 1926-2018 The discovery of IgE and the revolution in the
      study of allergic disease.

PMID- 30287255
TI  - Concordance of skin prick test and serum-specific IgE to locally produced
      component-resolved diagnostics for cockroach allergy.
AB  - BACKGROUND: Diagnosis of Periplaneta americana (American cockroach, ACR) allergy
      is commonly performed based on clinical history and skin prick test (SPT) or
      specific serum IgE (sIgE) measurement. The concordance of the findings with the
      SPT and sIgE results has never been investigated. OBJECTIVE: To compare the
      results of SPT with commercial ACR-extract (C-ACE) and sIgE measurement, using
      commercial kit and in-house enzyme-linked immunosorbent assay (ELISA) to the
      locally produced ACR extract (L-ACE) and native Per a 1, Per a 5, Per a 7, and
      Per a 9. METHODS: Sera from 66 individuals clinically diagnosed with chronic
      allergic rhinitis were included; 46 were positive SPT to C-ACE, and 20 were
      negative. Specific serum IgE levels were established by using a commercial test
      kit (ImmunoCap) and an in-house IgE-ELISA RESULTS: The percentage the C-ACE SPT
      positive cases that were positive by the ImmunoCap-sIgE was 32.6%, indicating low
      concordance of the 2 assays. With the in-house ELISA, Per a 9 gave the highest
      sensitivity (98.00%), positive predictive value (PPV; 95.74%), and negative
      predictive value (NPV; 94.74%) of the sIgE quantification. The correlation
      coefficients (R) of the L-ACE-SPT and sIgE to L-ACE, Per a 1, Per a 5, Per a 7,
      and Per a 9 and ImmunoCap sIgE were 0.133, 0.278, 0.419, 0.280, and 0.432, and
      0.256, respectively. CONCLUSION: Skin prick test and sIgE measurement using
      commercial reagents have low concordance. Data of this study showed that sIgE to
      the native Per a 9 should be considered as an adjunct to the clinical history in
      diagnosis of ACR sensitization/allergy, particularly when the SPT and the nasal
      challenge, which is the gold standard method, cannot be performed.

PMID- 30287257
TI  - Microscopic examination of urine sediment: Phase contrast versus bright field.
AB  - BACKGROUND: Today, phase contrast microscopy (PCM) is the recommended technique
      for manual urinary sediment (U-sed) examination. In fact, compared to bright
      field microscopy (BFM), it allows a better identification of most U-sed
      particles. METHODS: The main contributions, both as original papers in medical
      journals and as monographs on PCM applied to U-sed examination, published in the
      period 1950-1982 (which was chosen because it includes the results of the most
      important investigations on the subject) were identified and analysed. Moreover,
      a brief analysis on the use of PCM in U-sed examination today was carried out.
      RESULTS: After the discovery of PCM by the Dutch physicist Frits Zernike in the
      1930s, several contributions were published, most of which are forgotten today.
      All of them demonstrated the advantages of PCM over BFM in identifying the U-sed
      particles, especially casts, renal tubular epithelial cells, atypical urothelial
      cells associated with urothelial carcinoma, and erythrocytes (which for the 1st
      time were classified as dysmorphic - of glomerular origin - and isomorphic - of
      non glomerular origin). The analysis of six recent monographs on U-sed or
      urinalysis, written in English and with an international distribution,
      demonstrated that only in two of them the U-sed particles were mostly shown by
      PCM. CONCLUSION: Several papers and monographs, published since the early 1950s,
      have demonstrated the advantages of PCM over BFM for U-sed examination. In spite
      of this, PCM is not as widely used as it should be.

PMID- 30287258
TI  - Contribution of obesity as an effect regulator to an association between serum
      leptin and incident metabolic syndrome.
AB  - BACKGROUND: We investigated whether serum leptin can be a predictor for incident
      cases of MetS in a population-based study. METHODS: This is a prospective cohort
      study of 1590 adults aged between 40 and 70 years, who did not have MetS in 2005
      2008 (at baseline) and 2008-2011 (follow-up). The baseline serum leptin
      concentrations were measured by radioimmunoassay. RESULTS: During an average of
      2.8 years of follow-up, 113 men (17.1%) and 148 women (15.9%) developed MetS. In
      multivariable adjusted models, the odds ratio of incident MetS when comparing the
      lowest to the highest quartiles of leptin levels was 3.17 in men and 2.79 in
      women; nevertheless, the significance disappeared after adjusting for the body
      mass index (BMI). In subsidiary analyses by BMI, logistic regression analysis
      showed that subjects with the highest tertile of serum leptin level were 3.04 and
      2.12 times more likely to have MetS than those with the lowest tertile in lean
      subjects (OR 3.04; 95% CI 1.44-6.41; p = .004 in men vs. OR 2.12; 95% CI 1.06
      4.25; p = .036 in women, respectively). CONCLUSIONS: Obesity is an effect
      regulator, which can predict an association between increased serum leptin level
      and the incidence of MetS in lean subjects.

PMID- 30287259
TI  - An ELISA for quantifying GPIHBP1 autoantibodies and making a diagnosis of the
      GPIHBP1 autoantibody syndrome.
AB  - BACKGROUND: Autoantibodies against GPIHBP1, the endothelial cell transporter for
      lipoprotein lipase (LPL), cause severe hypertriglyceridemia ("GPIHBP1
      autoantibody syndrome"). Affected patients have low serum GPIHBP1 and LPL levels.
      We report the development of a sensitive and specific ELISA, suitable for routine
      clinical use, to detect GPIHBP1 autoantibodies in serum and plasma. METHODS:
      Serum and plasma samples were added to wells of an ELISA plate that had been
      coated with recombinant human GPIHBP1. GPIHBP1 autoantibodies bound to GPIHBP1
      were detected with an HRP-labeled antibody against human immunoglobulin.
      Sensitivity, specificity, and reproducibility of the ELISA was evaluated with
      plasma or serum samples from patients with the GPIHBP1 autoantibody syndrome.
      RESULTS: A solid-phase ELISA to detect and quantify GPIHBP1 autoantibodies in
      human plasma and serum was developed. Spiking recombinant human GPIHBP1 into the
      samples reduced the ability of the ELISA to detect GPIHBP1 autoantibodies. The
      ELISA is reproducible and sensitive; it can detect GPIHBP1 autoantibodies in
      samples diluted by >1000-fold. CONCLUSION: We have developed a sensitive and
      specific ELISA for detecting GPIHBP1 autoantibodies in human serum and plasma;
      this assay will make it possible to rapidly diagnose the GPIHBP1 autoantibody
      syndrome.

PMID- 30287261
TI  - Enzyme Replacement Therapy.

PMID- 30287260
TI  - Methylphenidate use in males with Duchenne muscular dystrophy and a comorbid
      attention-deficit hyperactivity disorder.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common comorbidity in
      Duchenne muscular dystrophy (DMD). Until now, treatment with methylphenidate
      (MPH) has never been systematically assessed and described in this population.
      Our aim was to evaluate the effectiveness and safety of short acting MPH for
      learning problems in males with DMD and ADHD. Neuropsychological (cognition and
      behavior) and medical data of a sample of ten males (mean age = 8.1 years, range
      6.3-9.8) with DMD and an ADHD diagnosis was retrospectively analyzed at baseline
      (T0; without MPH), short-term follow-up (T1; with MPH; mean interval T0-T1 = 8.3
      months, range 4.3-15.6), and long-term follow-up (T2; mean interval T1-T2 = 23.1
      months, range 2.6-77.7). An initial MPH dose of 5 mg/day was given on school
      mornings, with an increase of 2.5-5 mg/week depending on individual tolerance and
      treatment response, until a sufficiently effective dose was reached (range 0.2
      0.6 mg/kg/day). At T1, results demonstrated an improvement in attention (i.e.
      concentration, impulsivity, and distractibility) in four patients. Suboptimal
      effects were reported in four patients, and no effects in two patients. At T2,
      seven patients showed considerable improvement in attention. No major side
      effects were reported. Overall, our data show that short acting MPH can be
      clinically effective for learning problems in males with DMD and ADHD, with
      regular cardiac follow-up, and close monitoring of side effects and
      neuropsychological effects. Furthermore, this underscores the importance of the
      use of validated cognitive and behavioral measurement tools with adequate
      sensitivity to objectively evaluate the effect of MPH.

PMID- 30287262
TI  - Rehabilitation Therapy for Nursing Home Residents at the End-of-Life.
AB  - OBJECTIVE: Ultrahigh therapy use has increased in SNFs without concomitant
      increases in residents' characteristics. It has been suggested that this trend
      may also have influenced the provision of high-intensity rehabilitation therapies
      to residents who are at the end of life (EOL). Motivated by lack of evidence, we
      examined therapy use and intensity among long-stay EOL residents. DESIGN: An
      observational study covering a time period 2012-2016. SETTING AND PARTICIPANTS:
      New York State nursing homes (N = 647) and their long-stay decedent residents (N
      = 55,691). METHODS: Data sources included Minimum Data Set assessments, vital
      statistics, Nursing Home Compare website, LTCfocus, and Area Health Resource
      File. Therapy intensity in the last month of life was the outcome measure.
      Individual-level covariates were used to adjust for health conditions. Facility
      level covariates were the key independent variables of interest. Multinomial
      logistic regression models with facility random effects were estimated. RESULTS:
      Overall, 13.6% (n = 7600) of long-stay decedent residents had some therapy in the
      last month of life, 0% to 45% across facilities. Of those, almost 16% had very
      high/ultrahigh therapy intensity (>500 minutes) prior to death. Adjusting for
      individual-level covariates, decedents in the for-profit facilities had 18%
      higher risk of low/medium therapy [relative risk ratio (RRR) = 1.182, P < .001],
      and more than double the risk of high/ultrahigh therapy (RRR = 2.126, P < .001),
      compared to those with no therapy use in the last month of life. In facilities
      with higher physical therapy staffing, decedents had higher risk (RRR = 16.180, P
      = .002) of high/ultrahigh therapy, but not of low/medium therapy intensity. The
      use of high/ultrahigh therapy in this population has increased over time.
      CONCLUSIONS AND RELEVANCE: This is a first study to empirically demonstrate that
      facility characteristics are associated with the provision of therapy intensity
      to EOL residents. Findings suggest that facilities with a for-profit mission, and
      with higher staffing of therapists, may be more incentivized to maximize therapy
      use, even among the sickest of the residents.

PMID- 30287263
TI  - Long-term Impact of Hip Fracture on the Use of Healthcare Resources: a Population
      Based Study.
AB  - OBJECTIVES: To assess the impact of hip fracture (HF) on health care expenditures
      and resource use. DESIGN: Observational, retrospective study. An administrative
      registry was used to obtain sociodemographic, clinical, and expenditure data of
      patients treated in centers all over Catalonia (North-East Spain). SETTING AND
      PARTICIPANTS: Male and female patients aged 65 years or older admitted to a
      Catalonian hospital due to hip fracture (HF) between January 1 2012, and December
      31, 2016. MEASURES: The study data set included the expenditure and frequency of
      using nonemergency transport, rehabilitation, skilled nursing facility,
      specialist visits, admissions to the emergency department, hospitalization,
      pharmacy, and primary care. The patient status at each time point included living
      at home, staying in hospital, staying in a skilled nursing facility,
      institutionalized in a nursing home, and death. RESULTS: The record included
      38,628 patients (74.4% female) with a mean [standard deviation (SD)] age of 84.9
      (7.07) years. The average expenditure per patient during the first year after
      hospital admission was ?11,721.06, the index hospitalization being the leading
      expenditure (?4740.29). Expenditures related to hospitalization and skilled
      nursing facility remained higher than preinjury throughout the 3 years following
      HF. Three years after the index admission, 44.9% of patients had died, 39.7% were
      living in their homes, 14.2% were in a nursing home, 0.9% were in a skilled
      nursing facility, and 0.3% were in hospital. The expenditure of hospitalizations,
      primary care, and visits to the emergency department increased few months before
      the HF. CONCLUSIONS: In patients hospitalized for HF, the expenditure per patient
      decreases after hospital discharge but the use of healthcare resources is not
      restored to preinjury values. The increase of expenditures associated with
      primary care services, hospitalization, and emergency department services during
      the few months preceding hospital admission suggests a decline of health status
      in these patients.

PMID- 30287265
TI  - Nano-targeted relaxin impairs fibrosis and tumor growth in pancreatic cancer and
      improves the efficacy of gemcitabine in vivo.
AB  - Cancer-associated fibroblasts (CAFs), are the key effector cells in pancreatic
      ductal adenocarcinoma (PDAC), known to induce tumor growth and progression.
      Pancreatic stellate cells (PSCs) are the precursors of CAFs in PDAC that secrete
      abundant extracellular matrix, growth factors and cytokines. In this study, we
      targeted human relaxin-2 (RLX), an endogenous hormone, to PSCs to inhibit their
      differentiation into CAF-like myofibroblasts. RLX significantly inhibited TGF
      beta induced PSCs differentiation by inhibiting pSmad2 signaling pathway. In
      vitro in primary human PSCs (hPSCs), treatment with RLX dose-dependently
      inhibited the migration, contraction, and protein expression of alpha smooth
      muscle actin and collagen I These data demonstrate that RLX can regulate hPSCs
      activation in vitro. However, RLX has several drawbacks i.e. poor
      pharmacokinetics and systemic vasodilation, that limits its preclinical and
      clinical application. Thus, we designed and successfully synthesized a
      nanoparticle system by chemically conjugating RLX to superparamagnetic iron oxide
      nanoparticle (SPION) to improve its pharmacokinetics. Interestingly, we found RLX
      SPION to be more efficacious compared to free RLX in vitro. Significantly, we
      observed RLX-SPION retarded the tumor growth by itself and also potentiated the
      effect of gemcitabine in a subcutaneous co-injection (Panc1 and hPSCs) tumor
      model. The treatment resulted in significant inhibition in tumor growth, which
      was attributed to reduced collagen I (ECM), desmin (hPSC marker) and CD31
      (endothelial marker) expression. In contrast, free RLX showed no significant
      effects. Altogether, this study presents a novel therapeutic approach against
      tumor stroma using RLX-SPION to achieve an effective treatment against pancreatic
      tumor.

PMID- 30287264
TI  - The Change in Nursing Home Residents' Preferences Over Time.
AB  - OBJECTIVES: Nursing home (NH) residents' preferences for everyday living are the
      foundation for delivering individualized person-centered care. Yet, work has not
      examined what the most and least important preferences of nursing home residents
      are and if those preferences change over time. DESIGN: This study examined the
      change in nursing home residents' (n = 255) preferences for everyday living over
      a 3-month period. Participants were recruited from 28 NHs in the suburbs of a
      major metropolitan East Coast area of the United States. MEASURES: Residents were
      interviewed face-to-face using the Preferences for Everyday Living Inventory
      Nursing Home version at baseline (T1) and 3 months later (T2). Change was
      analyzed in 2 ways: (1) percentage exact agreement (eg, respondent stated "very
      important" at both time points) and (2) percentage of preferences that remained
      either important or not important between T1 and T2. RESULTS: Sixteen preferences
      were rated as very or somewhat important by 90% or more of NH residents. With
      regard to the stability of preference ratings, findings demonstrate an average
      exact agreement of 59%, and an average important versus not important agreement
      of 82%. In addition, 68 of the 72 preferences had 70% or higher stability over
      time. In other words, the preference either remained "important" or "not
      important" to the NH resident 3 months later. Preferences in the domain of
      enlisting others in care had the least amount of change. CONCLUSION/IMPLICATIONS:
      This study highlights the most important everyday living preferences of NH
      residents and provides assurance to care providers that the majority of
      preferences assessed via the PELI are both important to NH residents and stable
      over time. Preference-based care plans can be designed and used over a 3-month
      period with confidence by providers.

PMID- 30287266
TI  - The application of nanotechnology in immune checkpoint blockade for cancer
      treatment.
AB  - Cancer immunotherapy, which could utilize the host's immune system to kill tumor
      cells, has great potential in long-term inhibition of tumor growth and recurrence
      compared to chemotherapy and radiotherapy. As we know, tumors exhibit powerful
      adaption to escape the destruction of immune system at the late stage of diseases
      due to overactivation of immune checkpoint pathways which function as natural
      "brakes" for immune responses. The newly emerging immune checkpoint inhibitors
      are regarded as the breakthrough for cancer immunotherapy as they can re-boost
      the host's immune system by restoring T cells function and promoting cytotoxic T
      lymphocytes (CTLs) responses. However, there is still scope for improvement in
      enhancing the clinical efficacy and reducing side effects of these immune
      modulators. In this review, we mainly introduce the basic mechanisms of the
      immune checkpoint pathways and outline the recent successes of immune checkpoint
      blockade (ICB) therapy in combination with nanoparticle delivery system.
      Furthermore, the underexplored potential in application of nanotechnology to
      enhance the efficacy of immune checkpoint therapy and overcome the limits of
      immune checkpoint inhibitors is also discussed.

PMID- 30287267
TI  - Exosomes as adjuvants for the recombinant hepatitis B antigen: First report.
AB  - Over the past few years, exosomes, a class of extracellular vesicles (EVs), have
      emerged as key players for inter-cellular communication ultimately modulating the
      behavior of target cells with countless outcomes. Nevertheless, the potential
      role of exosomes as vaccine adjuvants remains largely unexplored. Herein, we
      hypothesized that exosomes derived from immune cells may have an
      immunostimulatory effect and could constitute a good target towards the
      development of new fine-tuned vaccine adjuvants. To accomplish this goal,
      exosomes isolated from lipopolysaccharide endotoxin (LPS)-stimulated human
      monocytic cell line (THP-1) were characterized and tested for their non-specific
      immunostimulatory activity when administered subcutaneously to healthy mice;
      additionally, exosomes' vaccine adjuvant ability was also disclosed after their
      inclusion in vaccine formulations. The results obtained suggested that the
      isolated exosomes evoked a pro-inflammatory profile in spleen cells of healthy
      mice through the induction of cytokines such as tumor necrosis factor alpha (TNF
      alpha), chemokine (C-C motif) ligand 5 (CCL5, also known as RANTES) and
      interleukin 1 beta (IL-1beta). Moreover, subcutaneous vaccination of mice with
      exosomes combined with a solution of hepatitis B recombinant antigen (HBsAg) or
      combined with a suspension containing HBsAg loaded poly-epsilon-caprolactone
      (PCL)/chitosan nanoparticles (NPs), induced a humoral immune response quite
      similar to the one achieved with the experimental control group (HBsAg solution
      without exosomes). However, exosomes triggered an immunomodulator effect on the
      cellular immune response, highlighted by the enhancement of IFN-gamma secretion.
      To the best of authors knowledge, this is the first report describing extensively
      the role of unmodified exosomes as adjuvants and co-adjuvants for hepatitis B
      vaccination strategies.

PMID- 30287269
TI  - Cell cycle regulator, small silencing RNA, and segmentation patterning gene
      expression in relation to embryonic diapause in the band-legged ground cricket.
AB  - Insects enter diapause to synchronize their life cycle with biotic and abiotic
      conditions favorable for their development, reproduction, and survival. Adult
      females of the band-legged ground cricket Dianemobius nigrofasciatus (Orthoptera,
      Glyllidae) respond to environmental factors in autumn and lay diapause-destined
      eggs. The eggs arrest their development and enter diapause at a very early
      embryonic stage, specifically the cellular blastoderm. To elucidate the
      physiological mechanisms underlying this very early stage programmed
      developmental arrest, we investigated the cell division cycle as well as the
      expression of cell cycle regulators, small silencing RNAs, and segment patterning
      genes. The diapause embryo arrests its cell cycle predominantly at the G0/G1
      phase. The proportion of cells in the S phase of the cell cycle abruptly
      decreased at the time of developmental arrest, but further changes of the G0/G1
      and G2/M were later observed. Thus, cell cycle arrest in the diapause embryo is
      not an immediate event, but it takes longer to reach the steady state. We further
      elucidated molecular events possibly involved in diapause preparation and entry.
      Downregulation of Proliferating cellular antigen (PCNA; a cell cycle regulator),
      caudal and pumilio (cad and pum; early segmentation genes) as well as P-element
      induced wimpy testis (piwi) (a small silencing RNA) prior to the onset of
      developmental arrest was notable. The downregulation of PCNA, cad and pum
      continued even after entry into developmental arrest. In contrast to upregulation
      in non-diapause eggs, Cyclin D (another cell cycle regulator) and hunchback,
      Kruppel, and runt (gap and pair-rule genes) were downregulated in diapause eggs.
      These molecular events may contribute to embryonic diapause of D. nigrofasciatus.

PMID- 30287270
TI  - Chlordecone potentiates auto-immune hepatitis and promotes brain entry of MHV3
      during viral hepatitis in mouse models.
AB  - Chlordecone is an organochlorine used in the 1970's as a pesticide in banana
      plantations. It has a long half-life in the soil and can potentially contaminate
      humans and animals through food. Chlordecone targets, and mainly accumulates in,
      the liver, leading to hepatomegaly and neurological signs in mammals. Chlordecone
      does not cause liver injuries or any inflammation by itself at low doses, but it
      can potentiate the hepatotoxic effects of other chemicals and drugs. We studied
      the impact of chlordecone on the progression of acute hepatitis in mouse models
      of co-exposure to chlordecone with Concanavalin A or murine hepatitis virus type
      3. We examined the progression of these two types of hepatitis by measuring
      hepatic transaminase levels in the serum and inflammatory cells in the liver,
      liver histological studies. Amplified tremors presented in the MHV3- chlordecone
      mouse model had led us to study the expression of specific genes in the brain. We
      show that chlordecone amplifies the auto-immune hepatitis induced by Concanavalin
      A by increasing the number of liver NKT cells, which are involved in liver
      damage. Chlordecone also accelerated the death of mice infected by murine
      hepatitis virus and enhanced the entry of the virus into the cervical spinal cord
      in infected mice, leading to considerable neurological damage. In conclusion,
      chlordecone potentiates both the Concanavalin A-induced hepatitis and brain
      damage caused by an hepatotropic/neurotropic virus.

PMID- 30287268
TI  - The Anorexia Nervosa Genetics Initiative (ANGI): Overview and methods.
AB  - BACKGROUND: Genetic factors contribute to anorexia nervosa (AN); and the first
      genome-wide significant locus has been identified. We describe methods and
      procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international
      collaboration designed to rapidly recruit 13,000 individuals with AN and
      ancestrally matched controls. We present sample characteristics and the utility
      of an online eating disorder diagnostic questionnaire suitable for large-scale
      genetic and population research. METHODS: ANGI recruited from the United States
      (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was
      via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social
      and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based
      on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no
      lifetime history of disordered eating behaviors. To assess the positive and
      negative predictive validity of the online eating disorder questionnaire (ED100K
      v1), 109 women also completed the Structured Clinical Interview for DSM-IV
      (SCID), Module H. RESULTS: Blood samples and clinical information were collected
      from 13,363 individuals with lifetime AN and from controls. Online diagnostic
      phenotyping was effective and efficient; the validity of the questionnaire was
      acceptable. CONCLUSIONS: Our multi-pronged recruitment approach was highly
      effective for rapid recruitment and can be used as a model for efforts by other
      groups. High online presence of individuals with AN rendered the Internet/social
      media a remarkably effective recruitment tool in some countries. ANGI has
      substantially augmented Psychiatric Genomics Consortium AN sample collection.
      ANGI is a registered clinical trial: clinicaltrials.govNCT01916538;
      https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank
      3.

PMID- 30287271
TI  - Clinical evaluation of an MRI-to-ultrasound deformable image registration
      algorithm for prostate brachytherapy.
AB  - PURPOSE: Identifying dominant intraprostatic lesions (DILs) on transrectal
      ultrasound (TRUS) images during prostate high-dose-rate brachytherapy (HDR-BT)
      treatment planning is challenging. Multiparametric MRI (mpMRI) is the tool of
      choice for DIL identification; however, the geometry of the prostate on mpMRI and
      on the TRUS may differ significantly, requiring image registration. This study
      evaluates the efficacy of an in-house software for MRI-to-TRUS DIL registration
      (MR2US) and compares its results to rigid and B-Spline deformable registration.
      METHODS AND MATERIALS: Ten patients with intermediate-risk prostate cancer, each
      with mpMRI and TRUS data sets, were included in this study. Five radiation
      oncologists (ROs) with expertise in TRUS-based HDR-BT were asked to cognitively
      contour the DIL onto the TRUS image using mpMRI as reference. The contours were
      analyzed for concordance using simultaneous truth and performance level
      estimation algorithm. Similarity indices, DIL volumes, and distance between
      centroid positions were measured to compare the consensus contours against the
      contours from ROs and the automated algorithms; registration time between all
      contouring methods was recorded. RESULTS: MR2US registration had the highest dice
      coefficients among all patients with a mean of 0.80 +/- 0.13 in comparison to
      rigid (0.65 +/- 0.20) and B-Spline (0.51 +/- 0.30). The distance between centroid
      positions between simultaneous truth and performance level estimation contour and
      MR2US, rigid, and B-Spline contours were 5 +/- 2, 7 +/- 5, and 18 +/- 11 mm,
      respectively. The average registration time was significantly shorter for MR2US
      (11 +/- 2 s) and rigid algorithm (7 +/- 1 s) compared to ROs (227 +/- 27 s) and B
      Spline (199 +/- 38 s). CONCLUSIONS: The efficacy of integrating an MRI-delineated
      DIL into a TRUS-based BT workflow has been validated in this study. The MR2US
      software is fast and accurate enough to be used for DIL identification in
      prostate HDR-BT.

PMID- 30287272
TI  - Hemispheric mPFC asymmetry in decision making under ambiguity and risk: An fNIRS
      study.
AB  - The Iowa Gambling Task (IGT) is a commonly used task for testing decision-making
      under ambiguity (the early stage) and risk (the late stage). However, differences
      between the temporal dynamic signals underlying these two types of decision
      making as well as the hemispheric specificity of decision making during the IGT
      remain unknown. The present study sought to address this gap by focusing on the
      medial prefrontal cortex (mPFC), which plays an important role in decision-making
      across life domains. We used functional near-infrared spectroscopy (fNIRS) with
      high spatial and temporal resolution and measured oxy-hemoglobin concentration
      within the mPFC in 25 healthy participants who performed the IGT. Results showed
      that there are different activations of the right and left hemispheres of the
      mPFC during the different stages of IGT and types of decisions. This implies that
      the left and right mPFC can have different patterns of involvement in decision
      making, at least in IGT decisions, including making good (low risk) and bad (high
      risk) choices, under ambiguity and under risk conditions.

PMID- 30287273
TI  - Behavioural, metabolic and neurochemical effects of environmental enrichment in
      high-fat cholesterol-enriched diet-fed mice.
AB  - While chronic high-fat feeding has long been associated with the rising incidence
      of obesity/type 2 diabetes, recent evidence has established that it is also
      associated with deficits in hippocampus-dependent memory. In this regard,
      environmental enrichment (EE) is an animal housing technique composed of
      increased space, physical activity, and social interactions, which in turn
      increases sensory, cognitive, motor, and social stimulation. EE leads to improved
      cerebral health as defined by increased neurogenesis, enhanced learning and
      memory and resistance to external cerebral insults. In the present study, the
      impacts of environmental enrichment (EE) on Swiss mice fed a high-fat,
      cholesterol-enriched diet (HFECD; 20% fat and 1.5% cholesterol) were
      investigated. Here, we demonstrated that EE, when initiated 4 weeks after the
      beginning of HFECD in mice, prevents HFECD-induced spatial memory and object
      recognition impairment, which were tested in T-maze and object recognition tests.
      Although EE did not affect HFECD-induced weight gain or hypercholesterolaemia, it
      improved glucose tolerance. On the other hand, EE was unable to mitigate a
      decrease in brain-derived neurotrophic factor (BDNF) and IL-6 hippocampal levels
      induced by the HFECD. Overall, while our results reinforce the positive and
      neuroprotective effects of EE on cognition they do not support a role for EE in
      preventing the neurochemical changes induced by the HFECD. Based on clinical
      observations that nondiabetic individuals with mild forms of impaired glucose
      tolerance have a higher risk of cognitive impairments, one can speculate about
      the connection between the effects of EE on glucose intolerance and its effects
      on cognition.

PMID- 30287274
TI  - Terrestrial dispersal of invasive signal crayfish during vulnerable life stages.
AB  - 1. Aquatic invertebrates commonly disperse between waterbodies by flight, though
      some decapods can emigrate from the water and walk overland. 2. The signal
      crayfish (Pacifastacus leniusculus, Dana) is a highly invasive species that can
      survive for days to weeks out of water, though it is unclear to what extent
      vulnerable life stages, such as ovigerous females or juvenile crayfish,
      terrestrially emigrate. Understanding this behaviour is important to consider
      during the management of crayfish stocks, since a single ovigerous female could
      potentially introduce hundreds of hatchlings to a new waterbody, which could
      themselves disperse overland. 3. Here, in a laboratory study, we examined the
      terrestrial emigration tendency of juvenile crayfish and compared the terrestrial
      emigration behaviour and overland walking speed of ovigerous and non-ovigerous
      females. 4. Size had a significant influence on juvenile crayfish terrestrial
      emigration tendency, where only those larger than 16.6 mm (carapace length) left
      the water. Ovigerous and non-ovigerous female signal crayfish showed no
      significant difference in terrestrial emigration tendency nor overland walking
      speed. 5. This is the first study to directly examine the terrestrial emigration
      behaviour of crayfish during these different life stages. These findings
      highlight the importance of considering animal behaviour during management
      strategies.

PMID- 30287276
TI  - A case of small bowel obstruction due to infection with Bolbosoma sp.
      (Acanthocephala: Polymorphidae).
AB  - A case of small bowel obstruction caused by Bolbosoma sp. infection is reported.
      A 27-year-old woman admitted with abdominal pain was diagnosed as small bowel
      obstruction. Laparoscopic surgery revealed induration in jejunum at ca. 120 cm
      distal to the ligament of Treiz, attributed to a band connecting the serosa to
      the ascending mesocolon. Resected band contained an acanthocephalan accompanying
      foreign body reaction with abscess formation. The parasite belonged to the genus
      Bolbosoma, of which identification was made by DNA sequence analysis. This is the
      eighth case of Bolbosoma infection in humans, and the first one causing an ileus.

PMID- 30287275
TI  - Cardiometabolic assessment of lamin A/C gene mutation carriers: A phenotype
      genotype correlation.
AB  - AIMS: Mutations of the LMNA gene encoding lamin A/C induce heterogeneous
      phenotypes ranging from cardiopathies and myopathies to lipodystrophies. The aim
      of this study was to compare cardiometabolic complications in patients with
      heterozygous LMNA mutations at the 482nd codon, the 'hotspot' for partial
      lipodystrophy, with carriers of other, non-R482 LMNA mutations. METHODS AND
      RESULTS: This study included 29 patients with R482 LMNA mutations, 29 carriers of
      non-R482 LMNA mutation and 19 control subjects. Cardiac and metabolic phenotypes
      were compared between groups. A family history of either cardiac implantable
      electronic devices (CIEDs; P < 0.001) or sudden death (P < 0.01) was more
      frequent in non-R482 than R482 carriers. The non-R482 carriers also had more
      abnormalities on electrocardiography and received CIEDs more often than R482
      carriers (P < 0.001). On cardiac ultrasound, non-R482 patients had greater
      frequencies of left atrial enlargement (P < 0.05) and lower left ventricular
      ejection fractions (P < 0.01) than R482 carriers. In contrast, R482 carriers had
      lower BMI (P < 0.05), leptin (P < 0.01) and fat mass (P <  0.001), but higher
      intra-/total abdominal fat-mass ratios (P < 0.001) and prevalences of diabetes (P
      < 0.01) and hypertriglyceridaemia (P < 0.05) than non-R482 carriers, with a trend
      towards more coronary artery disease. However, non-R482 carriers had higher intra
      /total abdominal fat-mass ratios (P < 0.02) and prevalences of diabetes (P <
      0.001) and hypertriglyceridaemia (P < 0.05) than the controls. CONCLUSION: Non
      R482 carriers present more frequently with arrhythmias than R482 carriers, who
      twice as often have diabetes, suggesting that follow-up for laminopathies could
      be adjusted for genotype. Non-R482 mutations require ultra-specialized cardiac
      follow-up, and coronary artery disease should not be overlooked. Although
      overlapping phenotypes are found, LMNA mutations essentially lead to tissue
      specific diseases, favouring genotype-specific pathophysiological mechanisms.

PMID- 30287277
TI  - What Do the Guidelines Say for Metastatic Prostate Cancer Starting Androgen
      Deprivation Therapy? National Comprehensive Cancer Network, European Society for
      Medical Oncology, and European Association of Urology recommendations.
AB  - Clinical trial data forms the foundation of how we treat men with metastatic
      prostate cancer who are initiating therapy. However, clinical trial data does not
      answer everything; hence, good clinical practice, pragmatism, and occasionally
      extrapolation drives how we manage these patients. Fortunately, multiple
      international guideline committees meet regularly and offer clinical guidance. In
      this mini-review, we focus on the United States National Comprehensive Cancer
      Network, European Society for Medical Oncology, and European Association of
      Urology (EAU) recommendations for the initial treatment of metastatic prostate
      cancer.

PMID- 30287278
TI  - Ribosomal RACK1 promotes proliferation of neuroblastoma cells independently of
      global translation upregulation.
AB  - Neuroblastoma is the most frequent solid tumor among those diagnosed during
      infancy and like most tumors, it is characterized by elevated rates of cell
      proliferation, migration and invasion. RACK1 is among the top 10 genes identified
      for unfavorable prognosis at 5 years in neuroblastoma cases and its depletion
      negatively affects proliferation, invasion and migration. Here, we show that the
      ribosomal localization of RACK1 modulates the proliferation of SH-SY5Y
      neuroblastoma cells by regulating the expression of cell cycle genes, such as
      Cyclin D1, D3 and B1 independently of global translation increase. Ribosomal
      RACK1 is not involved in general protein synthesis, which is instead dependent on
      total RACK1 and PKC but independent from mTOR. Thus, ribosomal RACK1 may
      represent a new target to develop more efficient therapies for neuroblastoma
      treatment.

PMID- 30287279
TI  - Epidermal growth factor can signal via beta-catenin to control proliferation of
      mesenchymal stem cells independently of canonical Wnt signalling.
AB  - Bone marrow mesenchymal stem/stromal cells (MSCs) maintain bone homeostasis and
      repair through the ability to expand in response to mitotic stimuli and
      differentiate into skeletal lineages. Signalling mechanisms that enable precise
      control of MSC function remain unclear. Here we report that by initially
      examining differences in signalling pathway expression profiles of individual MSC
      clones, we identified a previously unrecognised signalling mechanism regulated by
      epidermal growth factor (EGF) in primary human MSCs. We demonstrate that EGF is
      able to activate beta-catenin, a key component of the canonical Wnt signalling
      pathway. EGF is able to induce nuclear translocation of beta-catenin in human
      MSCs but does not drive expression of Wnt target genes or T cell factor (TCF)
      activity in MSC reporter cell lines. Using an efficient Design of Experiments
      (DoE) statistical analysis, with different combinations and concentrations of EGF
      and Wnt ligands, we were able to confirm that EGF does not influence the Wnt/beta
      catenin pathway in MSCs. We show that the effects of EGF on MSCs are temporally
      regulated to initiate early "classical" EGF signalling mechanisms (e.g via
      mitogen activated protein kinase) with delayed activation of beta-catenin. By RNA
      sequencing, we identified gene sets that were exclusively regulated by the
      EGF/beta-catenin pathway, which were distinct from classical EGF-regulated genes.
      However, subsets of classical EGF gene targets were significantly influenced by
      EGF/beta-catenin activation. These signalling pathways cooperate to enable EGF
      mediated proliferation of MSCs by alleviating the suppression of cell cycle
      pathways induced by classical EGF signalling.

PMID- 30287280
TI  - Development of photosynthetic sutures for the local delivery of oxygen and
      recombinant growth factors in wounds.
AB  - Surgical sutures represent the gold standard for wound closure, however, their
      main purpose is still limited to a mechanical function rather than playing a
      bioactive role. Since oxygen and pro-regenerative growth factors have been
      broadly described as key players for the healing process, in this study we
      evaluated the feasibility of generating photosynthetic sutures that, in addition
      to mechanical fixation, could locally and stably release oxygen and recombinant
      human growth factors (VEGF, PDGF-BB, or SDF-1alpha) at the wound site. Here,
      photosynthetic genetically modified microalgae were seeded in commercially
      available sutures and their distribution and proliferation capacity was
      evaluated. Additionally, the mechanical properties of seeded sutures were
      compared to unseeded controls that showed no significant differences. Oxygen
      production, as well as recombinant growth factor release was quantified in vitro
      over time, and confirmed that photosynthetic sutures are indeed a feasible
      approach for the local delivery of bioactive molecules. Finally, photosynthetic
      sutures were tested in order to evaluate their resistance to mechanical stress
      and freezing. Significant stability was observed in both conditions, and the
      feasibility of their use in the clinical practice was therefore confirmed. Our
      results suggest that photosynthetic gene therapy could be used to produce a new
      generation of bioactive sutures with improved healing capacities. STATEMENT OF
      SIGNIFICANCE: Disruption of the vascular network is intrinsic to trauma and
      surgery, and consequently, wound healing is characterized by diminished levels of
      blood perfusion. Among all the blood components, oxygen and pro-regenerative
      growth factors have been broadly described as key players for the healing
      process. Therefore, in this study we evaluated the feasibility of generating
      photosynthetic sutures that, in addition to mechanical fixation, could locally
      and stably release oxygen and recombinant human growth factors at the wound site.
      This novel concept has never been explored before for this type of material and
      represents the first attempt to create a new generation of bioactive sutures with
      improved regenerative capabilities.

PMID- 30287281
TI  - Bispecific applications of non-immunoglobulin scaffold binders.
AB  - Non-immunoglobulin scaffolds represent a proven group of small affinity proteins
      that can be engineered in vitro to similar affinity and potency as monoclonal
      antibodies. Several novel candidate biotherapeutics that exploit the potential
      advantages scaffold proteins hold over larger and more complex antibodies have
      been developed over the past decade. The ease of using small and robust binding
      proteins as flexible and modular building blocks has led to the development of a
      wide range of innovative approaches to combine them in various bi- and
      multispecific formats. This progress is expected to aid the ongoing challenge of
      identifying niche applications where clear differentiation from antibody-based
      molecules will be key to success. Given the many engineering options that are
      available for non-immunoglobulin scaffold proteins, they have potential to not
      only complement but probably also surpass antibodies in certain applications.

PMID- 30287282
TI  - Role of Toll-like receptor 4/oxidant-coupled activation in regulating the
      biosynthesis of omega-3 polyunsaturated fatty acid derivative resolvin D1 in
      primary murine peritoneal macrophage.
AB  - We have previously shown that reactive oxygen species (ROS) as prooxidants can
      activate Toll-like receptor 4 (TLR4) with the potential to initiate, propagate
      and maintain "sterile" inflammation of innate immunity, which plays a mediatory
      role in a host of human disease states. We now present new evidence that ROS can
      also activate TLR4 to counter the inflammatory phenotype by increasing the
      production of resolvin D1 (RvD1), which is a specialized anti-inflammatory and
      pro-resolving lipid mediator. We used primary murine peritoneal macrophages (pM)
      derived from both TLR4-WT and TLR4-KO mice as a cellular model. We used potassium
      peroxychromate (PPC) as a direct in vitro source of exogenous ROS. PPC treatment
      increased intracellular ROS levels, which decreased intracellular total
      antioxidant capacity, thus suggesting an enhanced cellular oxidative stress. PPC
      and LPS-EK (a TLR4-specific agonist) increased pro-inflammatory TNFalpha
      production with noeffect on IL-10, an anti-inflammatory cytokine. Treatment with
      the prooxidant increased the expression of 12 lipoxygenase (12-LOX) and 5
      lipoxygenase (5-LOX) only in pM derived from TLR4 WT but not in pM from TLR4-KO
      mice. 5-LOX and 12-LOX are the key enzymes in the RvD1 biosynthetic pathway. In
      addition, PPC increased the expression of RvD1 receptor, a member of G-protein
      coupled receptor only in pM from TLR4-WT mice. Our data support the involvement
      of TLR4-mediated oxidant-induced pro-inflammatory phenotypes that are in
      opposition to the production of anti-inflammatory/pro-resolution phenotypes in
      macrophages. Now, we show that through TLR4 activation, exogenous oxidants can
      play a role both in producing proinflammatory phenotypes at the same time that it
      enhances resolution of inflammation to maintain a state of cellular homeostasis
      and prevent tissue damage/disease.

PMID- 30287283
TI  - Models and methods for conditioning the ischemic brain.
AB  - BACKGROUND: In the last decades the need to find new neuroprotective targets has
      addressed the researchers to investigate the endogenous molecular mechanisms that
      brain activates when exposed to a conditioning stimulus. Indeed, conditioning is
      an adaptive biological process activated by those interventions able to confer
      resistance to a deleterious brain event through the exposure to a sub-threshold
      insult. Specifically, preconditioning and postconditioning are realized when the
      conditioning stimulus is applied before or after, respectively, the harmul
      ischemia. AIMS AND RESULTS: The present review will describe the most common
      methods to induce brain conditioning, with particular regards to surgical,
      physical exercise, temperature-induced and pharmacological approaches. It has
      been well recognized that when the subliminal stimulus is delivered after the
      ischemic insult, the achieved neuroprotection is comparable to that observed in
      models of ischemic preconditioning. In addition, subjecting the brain to both
      preconditioning as well as postconditioning did not cause greater protection than
      each treatment alone. CONCLUSIONS: The last decades have provided fascinating
      insights into the mechanisms and potential application of strategies to induce
      brain conditioning. Since the identification of intrinsic cell-survival pathways
      should provide more direct opportunities for translational neuroprotection
      trials, an accurate examination of the different models of preconditioning and
      postconditioning is mandatory before starting any new project.

PMID- 30287284
TI  - Kindlin-2 interacts with and stabilizes DNMT1 to promote breast cancer
      development.
AB  - Integrin-interacting protein Kindlin-2, as a focal adhesion protein, promotes
      growth and progression of breast cancer. However, the precise mechanism that
      underlie the role of Kindlin-2 in breast cancer is elusive. Here, we report that
      the expression of Kindlin-2 positively correlated with DNA methyltransferase
      1(DNMT1) in breast cancer patients. Further, we found that DNMT1 was upregulated
      in mammary gland tissues of mammary specific Kindlin-2 transgenic mice. More
      importantly, high expression of DNMT1 was observed in mammary tumors formed by
      Kindlin-2 transgenic mice. On the basis of these observations, DNMT inhibitor 5
      aza-CdR was used and found its treatment strongly decreased Kindlin-2-induced
      breast cancer cell proliferation and migration. Mechanistically, Kindlin-2
      increased the stability of DNA methyltransferase DNMT1 through interaction with
      DNMT1 and methylated CpG islands in the E-cadherin promoter. Kindlin-2 increased
      the occupancy of DNMT1 at E-cadherin promoter, thereby suppressing E-cadherin
      expression. Taken together, our data reveal that Kindlin-2 promotes breast cancer
      development by enhancing the stability of DNMT1.

PMID- 30287285
TI  - PAR2 Pepducin-Based Suppression of Inflammation and Itch in Atopic Dermatitis
      Models.
AB  - PAR2 has been proposed to contribute to lesion formation and intense itch in
      atopic dermatitis. Here, we tested the ability of a cell-penetrating pepducin, PZ
      235, to mitigate the potentially deleterious effects of PAR2 in models of atopic
      dermatitis. PZ-235 significantly inhibited PAR2-mediated expression of
      inflammatory factors NF-kappaB, TSLP, TNF-alpha, and differentiation marker K10
      by 94%-98% (P < 0.001) in human keratinocytes and suppressed IL-4 and IL-13 by
      68%-83% (P < 0.05) in mast cells. In delayed pepducin treatment models of
      oxazolone- and DNFB-induced dermatitis, PZ-235 significantly attenuated skin
      thickening by 43%-100% (P < 0.01) and leukocyte crusting by 57% (P < 0.05), and
      it inhibited ex vivo chemotaxis of leukocytes toward PAR2 agonists. Daily PZ-235
      treatment of filaggrin-deficient mice exposed to dust mite allergens for 8 weeks
      significantly suppressed total leukocyte and T-cell infiltration by 50%-68%;
      epidermal thickness by 60%-77%; and skin thickening, scaling, excoriation, and
      total lesion severity score by 46%-56%. PZ-235 significantly reduced itching
      caused by wasp venom peptide degranulation of mast cells in mice by 51% (P <
      0.05), which was comparable to the protective effects conferred by PAR2
      deficiency. Taken together, these results suggest that a PAR2 pepducin may confer
      broad therapeutic benefits as a disease-modifying treatment for atopic dermatitis
      and itch.

PMID- 30287286
TI  - Endovascular Treatment of a Late False Aneurysm Complicating Open Suprarenal
      Mycotic Aneurysm Repair with a Cryopreserved Aortic Homograft.
AB  - We report a patient who was initially treated for a suprarenal mycotic aortic
      aneurysm. The aneurysm repair was performed using a cryopreserved arterial
      homograft and debranching of visceral arteries. Five years later, the patient was
      referred due to a large symptomatic false aneurysm at the distal homograft
      anastomosis. Endovascular repair was indicated and performed using a bifurcated
      Medtronic composite stent graft. The procedure was uneventful, while control
      angiography showed complete exclusion of the false aneurysm. Within 6 months of
      follow-up, the endograft showed favorable position and maintained patency with no
      signs of endoleaks. We discuss the role of the cryopreserved homografts for in
      situ repair of mycotic aortic aneurysms and comment on possible late
      complications after placing those grafts.

PMID- 30287287
TI  - Aortic Surgery Outcomes of Marfan Syndrome and Ehlers-Danlos Syndrome Patients at
      Teaching and Nonteaching Hospitals.
AB  - BACKGROUND: Despite improvements in prevention and management, aortic aneurysm
      repair remains a high-risk operation for patients with Marfan syndrome (MFS) and
      Ehlers-Danlos syndrome (EDS). The goal of this study was to examine differences
      in characteristics and outcomes of patients with MFS or EDS undergoing aortic
      aneurysm repair at teaching versus nonteaching hospitals. METHODS: We used the
      National Inpatient Sample to study patients with MFS or EDS undergoing open or
      endovascular aortic aneurysm repair from 2000 to 2014. RESULTS: Of 3487 patients
      (MFS = 3375, EDS = 112), 2974 (85%) had repair at a teaching hospital. Patients
      who underwent repair at a teaching hospital were slightly younger than those who
      underwent repair at a nonteaching hospital (38 vs. 43 years, P < 0.01) but
      otherwise were similar in gender (29% vs. 28% female), race (70% vs. 78% white),
      and connective tissue disorder diagnosis (97% vs. 97% MFS, all P >= 0.1). There
      were no differences in anatomy (17% vs. 19% abdominal, 67% vs. 66% thoracic, and
      15% vs. 15% thoracoabdominal, all P >= 0.1) or type of repair (5% vs. 5%
      endovascular), but patients at nonteaching hospitals were more likely to have a
      dissection (49% vs. 38%, P = 0.02). There was no difference in perioperative
      mortality (4% vs. 6%, P = 0.5) or length of stay (median 8 days vs. 7 days, P =
      0.3) between teaching and nonteaching hospitals. There was also no difference in
      hemorrhagic (47% vs. 43%), pulmonary (9% vs. 16%), renal (12% vs. 14%), or
      neurologic (5% vs. 6%) complications between teaching and nonteaching hospitals,
      respectively (all P >= 0.05). In analysis stratified by anatomic extent of
      repair, there was a lower prevalence of pulmonary complications in thoracic aorta
      repairs at teaching hospitals (8.1% vs. 18.4%, P = 0.01) but a higher prevalence
      of hemorrhage in abdominal aortic repairs at teaching hospitals (45.6% vs. 20.6%,
      P = 0.04) as compared with nonteaching hospitals. CONCLUSIONS: Patients with MFS
      and EDS who undergo aortic aneurysm repair have their operations predominantly at
      teaching hospitals, but those patients who undergo repair at nonteaching
      hospitals do not have worse mortality or morbidity despite a higher incidence of
      dissection.

PMID- 30287288
TI  - Objective Performance Goals for Surgical Treatment of Critical Limb Ischemia.
AB  - BACKGROUND: Based on prospective vein bypass trials for lower leg ischemia,
      objective performance goals (OPG) were established by the Society for Vascular
      Surgery (SVS) and are used as a benchmark tool for open and endovascular
      treatments. This study aims to analyze OPG of all patients with critical limb
      ischemia (CLI) treated by open revascularization techniques at a tertiary care
      facility in routine practice. METHODS: From January 2005 to March 2013, 315
      patients (mean age 72 years) with CLI were retrospectively included in this
      study. Inclusion criteria were patients with Fontaine stage III and IV, realized
      revascularization with open surgical procedures (bypass grafting or
      endarterectomy), or hybrid method (open + endovascular). Exclusion criteria were
      primary major amputations, patients with revascularization treatments of the
      index leg within the last 3 months, and missing aftercare. Primary end point was
      "amputation-free survival" (AFS), and secondary end point was "freedom from major
      adverse limb event + perioperative death (30 days)" (MALE + POD) according to the
      SVS. The technical end point was primary patency. Mean follow-up was 34 months.
      The following variables were studied: clinical stage (Fontaine), previous
      interventions, bypass material used, and site of the distal anastomosis. The
      statistical evaluation and preparation was carried out using the Kaplan-Meier
      estimator and the log-rank test. A multivariate analysis was performed using the
      Cox proportional hazards model. A P value <=0.05 was considered to be
      statistically significant. RESULTS: A total of 128 patients (31%) fulfilling the
      adjusted SVS OPG criteria showed significantly better results for AFS, MALE +
      POD, and primary patency (P = 0.013, P = 0.015, P = 0.002, respectively).
      Regarding the AFS (1 year: 74%), multivariate analysis displayed significant
      worse results for patients with end-stage renal disease (hazard ratio [HR] 2.90,
      95% confidence interval [CI] 1.83-4.60, P < 0.001) and Fontaine stage IV (HR
      1.69, 95% CI 1.11-2.57, P = 0.015). Regarding MALE + POD (1 year: 64%), male
      patients (HR 0.64, 95% CI 0.46-0.90, P = 0.011) showed a significantly better
      outcome and patients without previous interventions of the index leg (HR 1.51,
      95% CI 1.09-2.09, P = 0.013) showed a significantly worse outcome. CONCLUSIONS:
      In this study, we were able to show that it is possible to reach the efficacy of
      OPGs set by SVS in a surgically treated all-comers cohort of CLI patients.
      Nevertheless, patients who did not fulfill the SVS OPG criteria showed
      significantly worse results for AFS and MALE + POD.

PMID- 30287289
TI  - Intraluminal Thrombus Deposition Is Reduced in Ruptured Compared to Diameter
      matched Intact Abdominal Aortic Aneurysms.
AB  - BACKGROUND: The aim of this study is to compare the pattern of intraluminal
      thrombus (ILT) deposition in diameter-matched ruptured and nonruptured abdominal
      aortic aneurysms (AAAs). METHODS: We performed a single-center, retrospective
      study. Ruptured AAAs were collected during 24 months. Diameter-matched intact
      lesions were randomly selected in a 2:1 ratio and served as controls. ILT cross
      sectional area, relative area, maximum thickness, and asymmetric distribution
      were recorded at the site of maximum aneurysm size and compared between groups.
      Moreover, additional comparisons were performed inside the group of ruptured
      AAAs, between the site of maximum size and the site of rupture. RESULTS: Fifteen
      ruptured cases were compared with 30 nonruptured cases. ILT relative area (37.5%
      vs. 73.5%, P = 0.004) and maximum thickness (14.5 vs. 28 mm, P= 0.0017) were
      significantly reduced among ruptured compared to intact AAAs. The latter group
      presented mostly an anterior eccentric ILT deposition, while the former presented
      a more symmetrical pattern. The site of rupture was located at the site of
      maximum size in only 2 cases. In general, ILT was reduced at the site of rupture
      compared to the site of maximum aneurysm size in ruptured cases but differences
      did not reach statistical significance. CONCLUSIONS: In similar sized AAAs, ILT
      is reduced in ruptured compared to nonruptured cases.

PMID- 30287290
TI  - Endovascular Management of a Distally Migrated Bifurcated Endograft with a New
      Bifurcated Endograft.
AB  - A 75-year-old man presented with abdominal and lumbar pain 6 years after previous
      endovascular repair of an abdominal aortic aneurysm. At the time of the initial
      operation, the aneurysm measured 6.0 cm in maximum diameter and a bifurcated
      Anaconda (Vascutek) endograft had been implanted. This time, computed tomography
      showed a distally migrated endograft which had been folded within the sac and the
      aneurysm measured 8.4 cm in maximum diameter. We opted to treat this by
      endovascular means deploying a new bifurcated endograft with suprarenal fixation
      within the old one. We consider the different management options and discuss the
      associated technical difficulties.

PMID- 30287291
TI  - Percutaneous Access of an Expanding Internal Iliac Artery Aneurysm via a Direct
      Posterior Transgluteal Approach.
AB  - BACKGROUND: Internal iliac artery aneurysms (IIAAs) are rare, comprising 0.3% of
      all aortoiliac aneurysms. Endovascular management is associated with lower
      morbidity and mortality than open repair. We present a 91-year-old female with a
      rapidly expanding 8.2-cm IIAA who previously underwent incomplete endovascular
      treatment, using endovascular aneurysm repair, to exclude the right internal
      iliac artery (IIA). Transarterial access to the IIAA was not possible secondary
      to the iliac limb of the endograft over the origin of the IIA. We recommended
      that the patient undergo embolization and coiling of the IIAA via a direct
      percutaneous transgluteal approach. METHODS: With the patient in a prone
      position, under fluoroscopic guidance, a 10-cm long, 18-gauge needle was placed
      through the gluteus muscle into the right IIAA. Needle location was confirmed by
      angiography and a 6-French sheath was advanced into the aneurysm. Selective
      catheterization of the native aorta was accomplished around the occluded limb of
      the previously placed endograft. Aortography confirmed robust filling of 2 large
      lumbar arteries with brisk runoff through branches of the IIA. Coil embolization
      was used to treat both the lumbar arteries causing aortic endoleak, as well as
      the outflow branches of the IIAA. RESULTS: Completion angiography revealed static
      flow in the aorta and aneurysm, with minimal flow through the inflow and outflow
      tracts. At a 1-month follow-up appointment, repeat computed tomography
      angiography revealed resolution of the endoleak and no blood flow within the
      aneurysm. There have only been a few case reports utilizing alternative access to
      an IIAA. Although computed tomography and ultrasound-guided techniques have been
      described in the literature, a percutaneous, fluoroscopy-guided, transgluteal
      approach to access the IIAA is a new and unique approach. CONCLUSIONS: In
      patients who are not candidates for open or standard endovascular repair with a
      large, inaccessible IIAA, a transgluteal approach to directly access the aneurysm
      sac may offer a less invasive and successful management strategy.

PMID- 30287292
TI  - Twelve-year Follow-up Post-Thoracic Endovascular Repair in Type B Aortic
      Dissection Shown by Three-dimensional Printing.
AB  - BACKGROUND: Thoracic endovascular repair (TEVAR) is currently considered the
      therapy of choice for complicated type B acute aortic dissection (TBAAD).
      Although several papers have reported good outcomes at short- and medium-term
      follow-up, some questions still remain regarding the long-term durability and re
      intervention rate during follow-up. METHODS: We describe a case of a patient
      originally treated with TEVAR for TBAAD complicated by impending aortic rupture.
      RESULTS: Endovascular repair successfully excluded the flow through the primary
      entry tear but during the 12-year follow-up period the patient experienced
      several complications and re-interventions. Various full-size three-dimensional
      (3D) models of the patient-specific vasculature were printed to better explain
      the different interventional interventions over the 12 years of follow-up and as
      a hands-on tool for medical education. CONCLUSIONS: The present case report,
      involving long-term follow-up, provides an example of the effectiveness and the
      safety of TEVAR for the treatment of complicated TBAAD shown at short and medium
      term follow-up. However, the long-term complications that were observed in this
      patient during follow-up support the importance of lifelong CTA surveillance.
      Furthermore, this study confirms the capability of 3D printing technology as a
      powerful tool to support communication with patients and residents' education
      through the physical analysis of the real cases.

PMID- 30287293
TI  - Iliac Aneurysms Treated with Endovascular Iliac Branch Device: A Systematic
      Review and Meta-analysis.
AB  - BACKGROUND: Iliac branch devices (IBDs) have been increasingly reported for
      treating aortoiliac aneurysms. However, there are still concerns regarding this
      device. The aim of this study was to evaluate the safety and outcomes of IBDs in
      treating aortoiliac aneurysms by performing a systematic review and meta
      analysis. METHODS: The Medline, EMBASE, and Cochrane databases were
      systematically searched to identify studies on the management of aortoiliac
      aneurysms using IBDs. Studies were reviewed and selected using defined criteria
      by 2 independent investigators who abstracted data on the study characteristics,
      study quality, and outcomes. The extracted data were presented as a rate and
      converted through arcsine transformations. Individual studies were evaluated and
      analyzed for 7 outcomes, including technical success rate, 30-day mortality, 30
      day patency, follow-up patency, endoleak rate, buttock claudication, and IBD
      associated reintervention. The heterogeneity of the studies was determined using
      the chi-squared distribution-based Q test and quantified by I2 statistics. Meta
      analyses were performed using both a random effects model and fixed effects
      model. RESULTS: Twenty-two studies with a total of 1064 patients met the
      inclusion criteria and were selected for analysis. The pooled technical success
      rate of IBD was 93% (95% confidence interval [CI]: 91-95%). After patients were
      treated with the IBD, the 30-day mortality rate was 2% (95% CI, 1-4%), 30-day
      patency rate was 93% (95% CI, 91-94%), follow-up patency was 86% (95% CI, 84
      88%), endoleak rate was 12% (95% CI, 8-17%), buttock claudication rate was 6%
      (95% CI, 5-8%), and IBD-associated reintervention rate was 11% (95% CI, 8-14%).
      CONCLUSIONS: Our study demonstrates that treating aortoiliac aneurysm with IBD
      produces satisfactory outcomes in midterm follow-up.

PMID- 30287294
TI  - Endovascular Stent-graft Repair of Combined Renal Artery Aneurysm and
      Arteriovenous Fistula.
AB  - Renal artery aneurysm with concomitant presence of arteriovenous fistula is an
      extremely rare entity. Few reports have been described in the literature.
      Nowadays, endovascular repair with covered stents or transarterial embolization
      with coils or glue has become the first line of treatment. We present the
      successful repair of a distal renal artery aneurysm combined with arteriovenous
      fistula with stent graft.

PMID- 30287295
TI  - Risk Factor Analyses of Abdominal Aortic Aneurysms Growth in Japanese Patients.
AB  - BACKGROUND: This study aimed to retrospectively demonstrate the growth rate
      (mm/year) of abdominal aortic aneurysm (AAA) diameters (ADs) and to analyze risk
      factors for AAA expansion. METHODS: We retrospectively investigated the clinical
      data of 319 patients with AAAs who were followed up as outpatients for >2 years
      after their initial visit and who underwent computed tomography >4 times.
      RESULTS: The mean follow-up period was 3.7 +/- 1.5 years. The annual average
      growth rates according to varying ADs were as follows: 1.9 +/- 0.8 (AD 30-34 mm),
      2.6 +/- 1.2 (AD 35-39 mm), 2.8 +/- 1.1 (AD 40-44 mm), 3.1 +/- 1.3 (AD 45-49 mm),
      3.4 +/- 1.6 (AD 50-54 mm), and 3.5 +/- 1.4 mm (AD >=55 mm). Factors associated
      with AAA expansion were smoking (P = 0.017), hypertension (P < 0.001), and ADs (P
      < 0.001). In the subgroup analysis, data regarding growth rates of >=3 mm were
      extracted, and a statistically significant difference between smoking status and
      ADs of >=40 mm was observed. CONCLUSIONS: Factors associated with AAA expansion
      in Japanese patients included smoking, hypertension, and ADs, and a statistically
      significant difference was observed between smoking status and ADs of >=40 mm.

PMID- 30287296
TI  - Retrograde Use of Gore Hybrid Vascular Graft for a Complex Carotid Tandem Lesion.
AB  - BACKGROUND: Successful treatment of tandem lesions of carotid arteries may
      represent a challenging goal for the vascular specialist. In the "endovascular
      era," a hybrid approach may represent a viable option. CASE REPORT: We describe
      the case of a 65-year-old patient with severe postcarotid endarterectomy
      recurrent stenosis of the internal carotid artery (ICA) associated with primitive
      stenosis of the proximal common carotid artery (CCA) treated with retrograde
      stenting and carotid bypass using the Gore Hybrid Vascular Graft (GHVG).
      CONCLUSIONS: We demonstrated the effectiveness of the hybrid technique using GHVG
      in treating carotid tandem lesions involving CCA and ICA.

PMID- 30287297
TI  - Duplex-guided versus Conventional Percutaneous Transluminal Angioplasty of Iliac
      TASC II A and B Lesion: A Randomized Controlled Trial.
AB  - BACKGROUND: Percutaneous transluminal angioplasty (PTA) requires the use of
      nephrotoxic contrast. Patients with chronic kidney disease are more prone to
      develop contrast-induced nephropathy after utilization of contrast. Doppler
      ultrasound (duplex)-guided PTA (DuPTA) is a novel technique and has recently
      proven to be a successful alternative to conventional PTA in the treatment of
      iliac stenotic disease, without the use of contrast. In this randomized
      controlled trial, we evaluated whether DuPTA is as effective as conventional PTA
      in the treatment of iliac arterial stenotic disease. METHODS: From June 2013 till
      January 2017, 142 patients with symptomatic peripheral arterial disease (PAD),
      with significant (>70%) iliac stenotic lesions (both isolated and patients with
      multilevel disease without treatment of other lesions), were randomized to
      receive either conventional PTA or DuPTA of the iliac lesion, regardless of renal
      function. All patients received an ankle-brachial index, arterial mapping with
      duplex, and magnetic resonance angiography in the pre-operative work-up. Primary
      end point was procedural success, defined as passing the guidewire through the
      stenotic lesion and performing a PTA, with or without stenting. Reduction in peak
      systolic velocity (PSV) of >=50% after successful PTA was required in the DuPTA
      group. Angiographic reduction of more than 50% was required in the interventional
      group. Decrease in PSV was evaluated in both groups 4 weeks post-procedure.
      RESULTS: Passing of the guidewire through the stenotic lesion was achieved in
      96.5% of the DuPTA group and 98.8% of the PTA group (P = 0.34). Although PSV
      decreased significantly in both groups 4 weeks post-operative, PSV reduction
      >=50% was significantly higher in the DuPTA group, respectively 78% vs. 58% in
      the PTA group (P < 0.01). The utilization of stents was significantly greater in
      the DuPTA group (52% vs. 18%, P < 0.01). After correction of potential
      confounders, significant difference in >=50% PSV reduction remained; technical
      success did not differ significantly. CONCLUSIONS: DuPTA is a feasible
      alternative to conventional PTA in the treatment of PAD on the iliac anatomic
      level. Duplex examination before removal of the guidewire is recommended to
      evaluate adequate decrease in PSV and identify potential recoil.

PMID- 30287298
TI  - External Iliac Artery Endofibrosis in a Female Cyclist: A Case Report.
AB  - External iliac artery endofibrosis is a rare disease described mainly in male
      endurance athletes. It presents as claudication of the lower limb during near
      maximum effort. The patients lack the usual risk factors for atherosclerosis,
      which makes diagnosis challenging. We present a case of external iliac artery
      endofibrosis in a female competitive cyclist. The initial surgical management was
      complicated by early recurrence due to intimal hyperplasia. After secondary drug
      eluting balloon angioplasty, the patient was able to resume competition. As such,
      it is important to maintain a high index of suspicion when evaluating a patient
      presenting with claudication symptoms in this setting. Primary treatment is
      surgical, and in cases of early recurrence angioplasty may be indicated. Most
      patients can return to full activity after healing is complete.

PMID- 30287299
TI  - A dynamic system of brain networks revealed by fast transient EEG fluctuations
      and their fMRI correlates.
AB  - Resting state brain activity has become a significant area of investigation in
      human neuroimaging. An important approach for understanding the dynamics of
      neuronal activity in the resting state is to use complementary imaging
      modalities. Electrophysiological recordings can access fast temporal dynamics,
      while functional magnetic resonance imaging (fMRI) studies reveal detailed
      spatial patterns. However, the relationship between these two measures is not
      fully established. In this study, we used simultaneously recorded
      electroencephalography (EEG) and fMRI, along with Hidden Markov Modelling, to
      investigate how network dynamics at fast sub-second time-scales, accessible with
      EEG, link to the slower time-scales and higher spatial detail of fMRI. We found
      that the fMRI correlates of fast transient EEG dynamic networks show highly
      reproducible spatial patterns, and that their spatial organization exhibits
      strong similarity with traditional fMRI resting state networks maps. This further
      demonstrates the potential of electrophysiology as a tool for understanding the
      fast network dynamics that underlie fMRI resting state networks.

PMID- 30287300
TI  - Training emotion regulation through real-time fMRI neurofeedback of amygdala
      activity.
AB  - Being in control of one's emotions is not only desirable in many everyday
      situations but is also a great challenge in a variety of mental disorders.
      Successful intentional emotion regulation is related to down-regulation of
      amygdala activity. Training mental interventions supported by neurofeedback of
      one's own amygdala activity using real-time (rt-)fMRI might be beneficial for
      mental health and well-being. Rt-fMRI guided amygdala-downregulation using
      cognitive interventions such as a "reality check", however, have not been well
      investigated. Fifteen healthy subjects underwent four rt-fMRI sessions with
      neurofeedback of their own amygdala activity while applying a reality check as an
      emotion regulation strategy in order to down-regulate their amygdala signal
      during a stimulation with emotional pictures. The Control group comprised of
      eleven subjects also trained emotion regulation but without obtaining feedback.
      We hypothesized more prominent down-regulation of amygdala activity at the end of
      the training in the Feedback group. We investigated effects over time and between
      groups and further task specific connectivity of the amygdala by using
      psychophysiological interaction analyses. Four weekly amygdala-based feedback
      sessions resulted in significantly decreased amygdala activity (p = 0.003, d =
      0.93), also compared to the Control group (p = 0.014, d = 1.12). Task specific
      connectivity of the amygdala with the anterior cingulate cortex, hippocampus and
      distinct prefrontal areas was increased in the Feedback group. Training of
      emotion regulation supported by rt-fMRI neurofeedback resulted in a prominent
      amygdala down-regulation compared to training without feedback. The finding
      implicates successful emotion regulation, compliant with emotion control models,
      through an easily applicable reality check strategy. Rt-fMRI neurofeedback may
      support emotion regulation learning and bears clinical potential for
      psychotherapy.

PMID- 30287302
TI  - Perceived timing of active head movement at different speeds.
AB  - The central nervous system must determine which sensory events occur at the same
      time. Actively moving the head corresponds with large changes in the relationship
      between the observer and the environment, sensorimotor processing, and
      spatiotemporal perception. Active head movement perception has been shown to be
      dependent on head movement velocity where participants who move their head
      fastest require the head to move earlier than comparison stimuli for perceived
      simultaneity more so than those who move their head slower. Such between-subject
      results cannot address whether active head movement perception changes with
      velocity. The present study used a within-subjects design to measure the point of
      subjective simultaneity (PSS) between active head movement speeds and a
      comparison sound stimulus to characterize the relationship between the velocity
      and perception of head movement onset. Our results clearly show that i) head
      movement perception is faster with faster head movements within-subjects, ii)
      active head movement onset must still precede the onset of other sensory events
      (average PSS: -123 ms to -52 ms; median PSS: -42 ms to -100 ms) in order to be
      perceived as occurring simultaneously even at the fastest speeds (average peak
      velocity: 76 degrees /s-257 degrees /s; median peak velocity 72 ms-257 ms). We
      conclude that head movement perception is slow, but that this delay is minimized
      with increased speed. These within-subject results are contrary to previous and
      present study between-subject results and are in agreement with literature where
      perception of auditory, visual and vestibular stimulus onset is less delayed with
      increased stimulus intensity.

PMID- 30287301
TI  - Community and household-level socioeconomic disadvantage and functional
      organization of the salience and emotion network in children and adolescents.
AB  - Socioeconomic disadvantage (SED) during childhood has been linked to disparities
      in physical and mental health. A growing body of research has focused on
      identifying neurodevelopmental consequences of SED, commonly measured using
      within-household factors (e.g., household income), to better understand the
      processes underlying SED-related disparities. These studies suggest that
      childhood SED has a widespread impact on brain development, altering development
      of multiple brain regions simultaneously. These findings also raise the
      possibility that childhood SED impacts development of key brain systems, such as
      the salience and emotion network (SEN), which is positioned at the intersection
      of brain systems involved in cognitive and emotion-related functioning and is
      thought to mediate information flow within and between these networks. The
      present study tests for associations between household- and community-level SED,
      as well as their interaction, and measures of SEN-based functional neural
      organization in 57 children and adolescents (ages 6-17). We applied graph
      theoretical analyses to resting-state functional magnetic resonance imaging
      (fMRI) data to examine SEN-based functional network topology. Results showed that
      youth residing in more distressed communities demonstrate lower hub-like
      properties (i.e., less efficient global information transfer and fewer
      connections) of two core SEN nodes - the anterior cingulate cortex and the left
      supramarginal gyrus. Similarly, lower household income was associated with lower
      efficiency of the anterior cingulate, but had no effect on the supramarginal
      gyrus. There was, however, an interaction between income and community SED in the
      rostral prefrontal cortex, such that higher income was associated with higher
      clustering coefficient and lower betweenness centrality, suggesting greater local
      processing and lower influence of this region on information flow across the
      network. These effects were significant only among youth living in low (but not
      high) SED communities, suggesting that within-household SED factors may not
      protect against the detrimental effects of a disadvantaged community context.
      Similarly, the age-related increase in average path length of the left rostral
      prefrontal cortex was only significant among youth living in low (but not high)
      SED communities. Given that maturation of the SEN is considered to be a critical
      functional backbone supporting the development of more flexible cognitive and
      emotional processes into adulthood, we tested for links between SEN graph metrics
      and measures of cognitive and emotion-related functioning. We found that higher
      community SED and lower income were both associated with lower IQ. Lower IQ, in
      turn, was associated with global efficiency of the left supramarginal gyrus.
      Observed effects of SED on SEN-based functional neural organization may help to
      explain the strong and pervasive link between childhood SED and disparities in
      cognitive and emotional outcomes.

PMID- 30287303
TI  - Gait bradykinesia and hypometria decrease as arm swing frequency and amplitude
      increase.
AB  - People with Parkinson's disease (PD) have decreased arm swing movements during
      walking, which can be related to PD motor signs and symptoms. In this context,
      the aim of this study was to determine the effects of an increased arm swing
      frequency or amplitude on the gait parameters in people with PD and healthy older
      adults. Seventeen individuals with PD and 19 older people were invited to walk on
      a 10 m pathway under three experimental conditions: (i) usual walking (no arm
      swing instructions); (ii) an increased arm swing amplitude; and (iii) an
      increased arm swing frequency. Both groups had an increased stride speed,
      vertical center of mass and arm swing accelerations and decreased double support
      time under the increased arm swing amplitude and frequency conditions. People
      with PD were able to modulate the gait parameters according to the experimental
      conditions, but at a smaller magnitude than the older individuals. These results
      indicate that bradykinesia and hypometria of gait can be positively overcome by
      increasing the amplitude and frequency of arm swing. Arm movements should be
      included in gait rehabilitation protocols for PD.

PMID- 30287304
TI  - Increased oxidation of RNA despite reduced mitochondrial respiration after
      chronic electroconvulsive stimulation of rat brain tissue.
AB  - Major depressive disorder (MDD) affects 350 million people worldwide and is a
      serious socio-economic burden. The most efficient treatment of MDD is
      electroconvulsive therapy (ECT), which has been shown to influence the oxidative
      status believed to be part of the pathophysiology of MDD. We investigated the
      effects of chronic electroconvulsive stimulation (ECS) on mitochondrial
      respiration and mitochondrial hydrogen peroxide production, RNA oxidation, and
      the content of mitochondria in the piriform cortex of the rat. We found
      reductions of mitochondrial respiration in respiratory states 2 and 3 by 33% and
      32%, respectively, and a 23% reduction in electron transfer capacity. RNA
      oxidation, as measured by 8-oxo-7,8-dihydroguanosine, was increased by 58%, while
      mitochondrial production of H2O2 was unaffected. The increased oxidative stress
      may thus be ascribed to extra-mitochondrial sources.

PMID- 30287305
TI  - Changes in multiunit activity pattern in cerebellar cortex associated to
      olfactory cues during sexual learning in male rats.
AB  - The cerebellum is a structure of the central nervous system which has been
      previously studied with different techniques and animal models and even humans,
      so it is associated with multiple functions such as cognition, memory, emotional
      processing, balance, control of movement, among others. Its relationship with
      sensory systems has already been explored, however, the role it plays in
      olfactory processing in the cerebellum is unclear. Several hypotheses have been
      proposed from work done in humans and animal models with neuroimaging and
      immunohistochemical techniques. Everything seems to indicate that the cerebellar
      function is of vital importance for the olfactory perception, being able to be
      controlling not only the olfactory aspect, but also the olfactory processing. In
      this study we analyzed the multiunit activity in the granular layer of the
      cerebellar vermis during olfactory stimulation: a session being sexually naive
      and during four sessions of sexual behavior learning. The amplitude was compared
      between male naive and sexual experts, as well as between olfactory stimuli. The
      amplitude of the sexually experienced rats showed the highest values compared to
      naive ones. Odor of receptive female causes the greatest amplitudes, however, in
      the control group the amplitude increased when they were sexually experts. The
      motor, sensory and associative learning generated by the acquisition of sexual
      experience modifies the activation pattern in the cerebellum by presenting
      neutral odors or associated with a reward.

PMID- 30287306
TI  - Repurposing of dexpramipexole to treatment of neonatal hypoxic/ischemic
      encephalopathy.
AB  - Dexpramipexole (DEX) is a drug with a good safety profile in humans, known for
      its ability to increase mitochondrial ATP production and prompt neuroprotection
      in adult rodents subjected to cerebral ischemia. In the present study we
      evaluated the effect of DEX in rat pups subjected to common carotid artery
      occlusion plus hypoxia (CCAoH, the classic Rice-Vannucci model). Because of the
      wide range of infarct size distribution in the CCAoH model, a priori subanalysis
      based on the effect of DEX on mild/moderate or severe brain injuries was
      conducted. The subanalysis showed that the drug (3 mg/kg bid i.p, after the
      hypoxic insult) decreased the infarction size in pups with mild/moderate
      injuries. Next, we developed a distal middle cerebral artery occlusion plus
      hypoxia (dMCAoH) model, characterized by an intra-experimental infarct size
      variability lower than that of the CCAoH model. Post-ischemic treatment with DEX
      (3 mg/kg bid i.p, after the hypoxic insult) reduced brain infarcts in pups
      exposed to dMCAoH. For the first time, we show that DEX reduces brain injury in
      different models of neonatal HIE. In light of the favorable safety profile of DEX
      in humans, the drug might have a realistic translational potential to treatment
      of perinatal cerebrovascular disorders.

PMID- 30287308
TI  - Beyond JAAD January 2019.

PMID- 30287307
TI  - Does acute heat stress differentially-modulate expression of ionotropic
      neurotransmitter receptors in the RVLM of young and aged F344 rats?
AB  - The rostral ventral lateral medulla (RVLM) is a brainstem area that plays a role
      in regulating numerous physiological systems, especially their responsiveness to
      acute stress. Aging affects the responsiveness of RVLM neural circuits to acute
      stress. Based on the relationship between ionotropic neurotransmitter receptors
      in the RVLM and the physiological functions mediated via activation of these
      receptors, we hypothesized that in response to acute heat stress the expression
      of ionotropic neurotransmitter receptors in the RVLM of aged rats would be
      characterized by upregulation of inhibitory subunits and downregulation of
      excitatory subunits. The goal of the present study was to determine the effect of
      acute heating on the gene expression profile of RVLM inhibitory (GABAA and
      Glycine) and excitatory (NMDA and AMPA) ionotropic neurotransmitter receptor
      subunits in young and aged F344 rats. RVLM tissue punches from young and aged
      F344 rats were analyzed using TaqMan qPCR and immunoblotting. When compared to
      age-matched controls, heat stress increased the gene expression of RVLM
      inhibitory receptor subunits in aged (Gabra1, Gabra2, Gabra5, Glra1) and young
      (Gabra1) F344 rats at mRNA level, with little change in the expression of RVLM
      excitatory receptor subunits. Significant age x heat interaction effects were
      observed with increased expression of Gabra2 and Gabrb1 inhibitory receptor
      subunits and decreased expression of Gria1 and Gria2 excitatory receptor subunits
      in the RVLM of aged F344 rats, with the most marked change observed with the
      Gabra2 subunit, which was validated by immunoblotting. These findings demonstrate
      that in response to acute heat stress there is enhanced expression of inhibitory
      ionotropic receptor subunits in aged compared to young rats, supporting the idea
      that advanced age may alter RVLM responsivity by affecting the molecular
      substrate of ionotropic receptors.

PMID- 30287309
TI  - A systematic review and meta-analysis of the regional and age-related differences
      of atopic dermatitis clinical characteristics.
AB  - BACKGROUND: Previous studies found conflicting results about the commonality of
      different atopic dermatitis (AD) signs and symptoms. OBJECTIVE: To determine the
      prevalences of AD characteristics and differences by region and age. METHODS: A
      systematic review was performed of all published studies in MEDLINE, EMBASE,
      SCOPUS, LILACS, Cochrane, China National Knowledge Infrastructure, Taiwan
      electronic periodical services and CiNii that analyzed the proportion of AD
      characteristics. Two reviewers performed study title/abstract review and data
      abstraction. RESULTS: One hundred and one studies reported proportion of AD
      features with sufficient data for meta-analysis. The most prevalent AD features
      were pruritus, lichenification and xerosis. There were differences of AD
      characteristics by study region. Flexural involvement was less commonly reported
      in India, America and Iran. East Asian studies reported more erythroderma,
      truncal, extensor, scalp and auricular involvement. Southeast Asian studies
      reported more exudative eczema, truncal involvement, lichenification and prurigo
      nodules. Studies from Iran reported more head, face and neck involvement,
      pityriasis alba, and xerosis. Studies from Africa reported more papular lichenoid
      lesions, palmar hyperlinearity, ichthyosis and orbital darkening. LIMITATIONS:
      Heterogeneity between studies and limited reporting of certain AD clinical
      characteristics. CONCLUSIONS: AD characteristics are heterogeneous and vary by
      region and age.

PMID- 30287310
TI  - Lower Socioeconomic Status is Associated with Delayed Access to Care for
      Infantile Hemangioma, a Cohort Study.
AB  - BACKGROUND: Early specialist evaluation during rapid proliferative growth of
      complicated infantile hemangiomas (IH) is crucial. Health disparities and
      barriers of access-to-care for children with IH have not been examined.
      OBJECTIVE: Investigate whether socioeconomic status (SES) is associated with age
      at subspecialist presentation for IH evaluation. METHOD: Retrospective cohort
      study of 804 children presenting to a large academic hospital. Primary outcome
      was age at initial presentation. Covariates included demographic, socioeconomic,
      geographic, and clinical characteristics. Medicaid or Children's Health Insurance
      Program (CHIP) were proxies for lower SES. Analysis of covariance, chi2 tests,
      and generalized ordered logistic regressions were performed. RESULTS: Children
      with lower SES had higher odds of presenting after 3 months of age (OR 2.11, 95%
      CI 1.31-3.38). In the subset that qualified for institutional care management
      program (ICMP), no risk factors were associated with delayed presentation.
      LIMITATIONS: Use of insurance and economic distress as proxies for SES; exclusion
      of uninsured children may underestimate racioethnic effects; single academic
      center study limiting generalizability. CONCLUSIONS: Children with IH and lower
      SES were more likely to present later to specialists, but those enrolled in an
      ICMP did not, suggesting that integrated ICMPs may mitigate disparities and
      delayed access-to-care for IH among lower SES populations.

PMID- 30287312
TI  - Correction.

PMID- 30287311
TI  - Association between atopic dermatitis and autoimmune disorders in US adults and
      children: A cross-sectional study.
AB  - BACKGROUND: Little is known about the risk and predictors of autoimmune diseases
      in children and adults. OBJECTIVE: To determine the prevalence, predictors and
      excess costs of autoimmune disease in AD patients. METHODS: Cross-sectional study
      of the 2002-2012 National Inpatient Sample, including a ~20% sample of all US
      hospitalizations (n=87,053,155 adults and children). RESULTS: The prevalence [95%
      confidence interval {CI95}] of autoimmune disease was higher in adults (7.9% [7.3
      8.5%] vs. 5.7 [5.7-5.8%]) and children (2.0% [1.7-2.3%] vs. 1.0% [0.9-1.1%]) with
      vs. without AD. In multivariable logistic regression models controlling for socio
      demographics, adult (adjusted odds ratio [CI95]: 1.45 [1.32-1.8]) and pediatric
      (2.08 [1.73-2.50]) AD were associated with any autoimmune disorder. In
      particular, AD was associated with 18 of 32 autoimmune disorders examined in
      adults and 12 of 24 examined in children, including disorders of the skin,
      endocrine, gastrointestinal, hematologic and musculoskeletal systems. AD patients
      hospitalized with any autoimmune disorder had higher cost of inpatient care with
      $2.5-$50 million excess annual costs. CONCLUSIONS: Adults and children with AD
      had increased cutaneous and extra-cutaneous autoimmune disorders, which were
      associated with a considerable cost-burden.

PMID- 30287313
TI  - Infertility and Teratogenicity after Paternal Exposure to Systemic Dermatologic
      Medications: A Systematic Review.
AB  - BACKGROUND: This systematic review assesses effects of paternal exposure of
      dermatologic medications, using the former US Food and Drug Administration (FDA)
      pregnancy categories as a benchmark. OBJECTIVE: To assess whether systemic
      dermatologic medications can cause infertility and teratogenicity when taken by
      men. METHODS: Category D and X dermatologic medications were identified; a
      systematic review of the literature and reviews of the FDA Adverse Events
      Reporting System (FAERS) and prescribing information were performed to identify
      effects on male fertility and teratogenicity. Secondary search was performed to
      assess for other systemic dermatologic medications causing teratogenicity or
      infertility following paternal exposure. RESULTS: Thirteen medications met
      inclusion criteria. Nineteen of 1,032 studies were included after systematic
      review of the literature. Studies evaluating medication effects with paternal
      exposure were identified for 10 of 13 evaluated medications, and evidence of a
      negative effect was identified for 6 medications. LIMITATIONS: We did not
      encounter any studies for 3 medications that met inclusion criteria. Information
      submitted to the FAERS may not reflect incidence of side effects. CONCLUSIONS:
      Many former pregnancy category D and X systemic dermatologic medications also
      have effects on male fertility. More research and better-quality studies are
      required in this area, particularly assessing potential teratogenicity.

PMID- 30287314
TI  - Guideline-based medicine grading on the basis of the guidelines of care for
      ambulatory atopic dermatitis treatment in the United States.
AB  - PURPOSE: This study was designed to assess the adherence to evidence-based
      guidelines of care for atopic dermatitis (AD). METHODS: To characterize AD
      treatment in the United States, ambulatory visits from the 2006-2015 National
      Ambulatory Medical Care Survey were analyzed. For each medication prescribed, a
      grade was assigned on the basis of the American Academy of Dermatology treatment
      guidelines for topical and systemic medications. Considering all visit
      prescriptions, I calculated a composite grade, analogous to the US academic
      grading system (scores A-F). RESULTS: I noted prescribing differences across
      specialty groups. Systemic corticosteroids were more likely to be prescribed by
      family and general physicians and less likely by pediatricians. Dermatologists
      were more likely than other specialties to prescribe nonsedating antihistamines,
      which lack a guideline base supporting their use. Depending upon modeling of care
      assumptions, all physician specialty visits earned mean guideline-based grades of
      B or C in their care of AD patients. LIMITATIONS: The clinical, social, and
      demographic factors influencing prescribing behavior cannot be completely
      assessed by using extant data. CONCLUSIONS: This preliminary study demonstrates
      that physicians might benefit from reviewing guidelines of care; there might be
      an educational gap in the implementation of these guidelines.

PMID- 30287315
TI  - Opioid Prescribing for Acute Postoperative Pain After Cutaneous Surgery.
AB  - BACKGROUND: Little information is available to predict which patients require
      opioid analgesia following cutaneous surgery. When opioids are indicated,
      information is lacking regarding the optimal opioid agent selection and dosage.
      OBJECTIVE: To make recommendations for opioid prescription after cutaneous
      surgery. METHODS: A PubMed literature search was conducted to review the
      available literature. Recommendations are presented on the basis of available
      evidence and the opinion of the authors. RESULTS: Most patients undergoing
      cutaneous surgery do not require opioid analgesia. For those who do, the pain
      duration warranting opioid analgesia is generally less than 36 hours. Opioid
      refill requests warrant a follow-up visit to ascertain the cause of ongoing pain
      after excisional procedures. LIMITATIONS: The recommendations are not based on
      prospective randomized trials. CONCLUSIONS: The presented recommendations for
      opioid prescription practice are derived from available evidence,
      recommendations, and expert opinion.

PMID- 30287316
TI  - Cost Analysis of a Store and Forward Teledermatology Consult System in
      Philadelphia.
AB  - BACKGROUND: Store-and-forward (SAF) teledermatology (TD) has the potential to
      increase access to timely, high-quality care for underserved populations.
      However, the cost-effectiveness of TD for underserved populations is uncertain.
      OBJECTIVE: This study evaluates the potential cost savings associated with a SAF
      TD program implemented for an underserved population in the city health clinics
      of urban Philadelphia. METHODS: We performed a retrospective analysis of SAF TD
      consultations for 700 outpatients managed in 12 Philadelphia primary care
      clinics. Primary care providers (PCPs) were asked to specify a treatment plan, as
      well as the type of care for the patient, in the absence of the TD service.
      Analysis compared cost of each patient case using the TD consult model versus
      conventional care. RESULTS: Twenty-seven percent (189/700) of in-person
      dermatology clinic visits and 3.29% (23/700) of emergency room (ER) visits were
      avoided using TD. Compared to conventional care, mean expected cost savings were
      $10.00-$52.65 per TD consult. In sensitivity analyses, these estimated savings
      remained positive across a range of parameters. LIMITATIONS: The cost analysis
      relies on several assumptions regarding the cost of care, and indirect costs were
      not included. CONCLUSION: Teledermatology can be a cost saving model while
      increasing access to dermatologic care.

PMID- 30287317
TI  - Gabor-Domain Optical Coherence Tomography to Aid in Mohs Resection of Basal Cell
      Carcinoma.

PMID- 30287318
TI  - The role of TERT promoter mutations in differentiating recurrent nevi from
      recurrent melanomas: a retrospective, case-control study.
AB  - BACKGROUND: Repigmentation at previous biopsy sites pose a significant diagnostic
      dilemma given clinical and histologic similarities between recurrent nevi and
      locally recurrent melanoma. While common in melanoma, the role of TERT promoter
      mutations (TPMs) in recurrent nevi is unknown. OBJECTIVE: We investigated the
      role of TPMs in recurrent nevi and whether the presence of hotspot TPM
      distinguishes recurrent nevi from locally recurrent melanoma. We also
      characterized clinical and histologic features differentiating these lesions.
      METHODS: We analyzed 11 locally recurrent melanomas, 17 recurrent nevi, and
      melanoma and nevus controls to determine TPM status. We also assessed clinical
      and histologic features of the recurrent groups. RESULTS: Hotspot TPMs were more
      common in recurrent melanomas compared to recurrent nevi (p=0.008). Recurrent
      melanomas were more likely to have solar elastosis (p=0.0047), multi-layering of
      melanocytes in the epidermis (p=0.0221), adnexal involvement (p=0.0069), and
      epidermal consumption (p=0.0204). Recurrent nevi had intra-epidermal atypia
      limited to the area above the scar (p<0.0001) and occurred earlier after the
      original biopsy (p<0.0008). Solar elastosis, months to recurrence, and hotspot
      TPM were independently associated with recurrent melanoma in multivariate
      analysis. LIMITATIONS: This was a retrospective study. CONCLUSION: Hotspot TPMs
      are significantly more frequent in recurrent melanomas and may serve as a
      diagnostic clue in histologically ambiguous cases.

PMID- 30287319
TI  - Trends in utilization of topical medications for treatment of rosacea in the
      United States (2005-2014) - a cohort analysis.

PMID- 30287320
TI  - Association of multiple primary melanomas with malignancy risk: a population
      based analysis of the Surveillance, Epidemiology, and End Results Program
      database from 1973-2014.
AB  - BACKGROUND: Genetic and environmental risk factors have been associated with the
      development of multiple primary melanomas (MPM). We hypothesized that individuals
      with MPM may have increased predisposition to developing internal malignancies.
      OBJECTIVE: To identify the risk of subsequent malignancies in MPM patients.
      METHODS: Multiple primary standardized incidence ratios were analyzed for
      individuals with >=1, >=2 and >=3 primary melanomas (PM) in the SEER database
      from 1973-2014. RESULTS: 223,799 individuals with >=1, 19,709 with >=2 and 3,995
      with >=3 PM were identified. Risks of subsequent internal malignancy increased
      with number of PM, with observed to expected (O/E) ratios of 0.99, 1.14, and 1.23
      (p<0.05) for patients with at least one, two and three PM respectively. Internal
      malignancy was higher in younger MPM patients and those with superficial
      spreading melanoma. The most common malignancies amongst MPM patients include
      breast, prostate, thyroid, soft tissue, brain, kidney, non-Hodgkin's lymphoma,
      and chronic lymphocytic leukemia. Risk of subsequent cutaneous melanoma increased
      with O/E ratios of 8.09, to 22.52, to 41.03 (p<0.05) respectively. LIMITATIONS:
      SEER records limited information about pigmentation phenotypes, histology, and
      treatments. CONCLUSION: Patients with MPM have increased risk of subsequent
      internal and cutaneous malignancies and may benefit from tight adherence to age
      specific cancer screening.

PMID- 30287321
TI  - Trends in the Incidence and Survival of Eccrine Malignancies in the United
      States: A SEER Population-Based Study.

PMID- 30287323
TI  - Prognostic value of the Breslow/diameter ratio in cutaneous melanoma.

PMID- 30287322
TI  - More than keratitis, ichthyosis, and deafness: multisystem effects of lethal GJB2
      mutations.
AB  - BACKGROUND: Infant death in KID syndrome is recognized; its association with
      specific genotypes and pathophysiology is inadequately understood. OBJECTIVE: To
      discover characteristics that account for poor outcomes in lethal KID syndrome.
      METHODS: We collected four new cases and nine previously reported, genotyped
      cases of lethal KID syndrome. We performed new molecular modeling of the lethal
      mutants GJB2 p.A88V and GJB2 p.G45E. RESULTS: Infant death occurred in all
      patients with GJB2 p.G45E and p.A88V; it is unusual with other GJB2 mutations.
      Early death with those two "lethal" mutations is likely multifactorial: during
      life all had at least one serious infection; most had poor weight gain and severe
      respiratory difficulties; many had additional anatomic abnormalities. Structural
      modeling of GJB2 p.G45E identified no impact on the salt bridge previously
      predicted to account for abnormal central CO2 sensing of GJB2 p.A88V.
      LIMITATIONS: Clinical review was retrospective. CONCLUSION: GJB2 p.G45E and
      p.A88V are the only KID syndrome mutations associated with uniform early
      lethality. Those electro-physiologically severe mutations in GJB2 reveal
      abnormalities in many organs in lethal KID syndrome. All KID syndrome patients
      may have subtle abnormalities beyond eyes, ears and skin. Early genotyping of KID
      syndrome births will inform prognostic discussion.

PMID- 30287324
TI  - "Treatment of male pattern alopecia with platelet-rich plasma: a double blind
      controlled study with analysis of platelet number and growth factor levels".
AB  - BACKGROUND: Promising results were described with platelet-rich plasma (PRP) in
      androgenetic alopecia that could be associated to platelet number and growth
      factor levels. OBJECTIVE: Analyze the platelet number and growth factor levels in
      PRP and its correlation with hair growth parameters evaluated by TrichoScan.
      METHODS: Twenty-six patients randomized to receive four subcutaneous injections
      of PRP or saline. Hair growth, hair density, and percentage of anagen hairs were
      evaluated before, after and three months after the last injection using
      TrichoScan method. Growth factors (PDGF, EGF and VEGF) were measured by Luminex
      method. RESULTS: We demonstrated a significant increase in hair count (p =
      0.0016), hair density (p = 0.012) and percentage of anagen hairs (p = 0.007) in
      PRP group when compared to control group, without correlation with platelet
      counts or quantification of the growth factors in PRP. CONCLUSION: Our data
      favors the use of PRP as therapeutic alternative in the treatment of androgenetic
      alopecia. The lack of association between platelet count, PDGF, EGF and VEGF
      levels and clinical improvement suggest that other mechanisms could be involved
      in this response. LIMITATIONS: Other growth factors that could be related with
      PRP response were not evaluated.

PMID- 30287325
TI  - Acne Disparities in Native Americans.

PMID- 30287327
TI  - Evaluating the cost-effectiveness of teldermatology.

PMID- 30287326
TI  - Bullae for you: The increasing importance and implications of drug-induced
      bullous pemphigoid.

PMID- 30287328
TI  - Overall and Subgroup Prevalence of Acne Vulgaris Among Patients with Hidradenitis
      Suppurativa.
AB  - BACKGROUND: Evidence establishing the link between acne vulgaris (AV) and
      hidradenitis suppurativa (HS) is limited, and the burden of AV in this group is
      unknown. OBJECTIVE: To determine prevalence of AV among adults with HS, and to
      determine the strength of this association. METHODS: Cross-sectional analysis
      identifying adults with AV among HS and non-HS patients using electronic health
      records data from a population-based sample of over 55 million patients. RESULTS:
      Prevalence of AV among adults with HS was 15.2% (7,315 /48,050), compared to 2.9%
      (497,360 /16,899,470) for adults without HS (p<0.001). Prevalence was greatest
      among HS patients who were female (5,870/35,790; 16.4%), ages 18-44 years
      (5,260/28,870; 18.2%), non-white (3,120/17,825); 17.5%), obese (5,430/35,135;
      15.5%), and had PCOS (685/2,385; 28.7%). HS patients had 4.51 [95% CI 4.40-4.63]
      times the odds of having AV compared to non-HS patients, and the higher
      likelihood of having AV persisted across all HS subgroups. The association
      between HS and AV was generally stronger for patients who were male, aged >= 65
      years, non-whites, and obese. LIMITATIONS: Influence of disease severity in HS,
      or in acne, on the strength of the association could not be assessed. CONCLUSION:
      Patients with HS may benefit from assessment of acne status and optimization of
      co-management strategies.

PMID- 30287329
TI  - Breastfeeding initiation and duration and child health outcomes in the first baby
      study.
AB  - Despite the known benefits of breastmilk, associations between breastfeeding and
      child overall health outcomes remain unclear. We aimed to understand associations
      between breastfeeding and health outcomes, including child weight, through age 3.
      Analysis included women (N = 3006) in the longitudinal, prospective First Baby
      Study from 2009 to 2014. For this analysis, breastfeeding initiation and duration
      were measured using self-reported data from the 1-, 6- and 12-month surveys;
      child illnesses were analyzed from the 6-, 12-, and 24-month interviews; height
      and weight at age 3 were used to determine overweight/obese (>=85th percentile)
      and obese (>=95th percentile). Adjusted logistic regressions were utilized to
      determine significance. Greater duration of breastfeeding was associated with
      fewer reported acute illnesses at 6 months (p < 0.001) and fewer diarrheal
      illness/constipation episodes at 6, 12, and 24 months (p = 0.05) in adjusted
      analyses. Fewer breastfed children, compared to non-breastfed children, were
      overweight/obese (23.5% vs. 37.8%; p = 0.032) or obese (9.1% vs. 21.6%; p =
      0.012) at age 3. Breastfeeding duration was negatively associated with
      overweight/obese (never breastfed: 37.8%, 0-6 months: 26.9%, >6 months: 20.2%; p
      = 0.020) and obesity (never breastfed: 21.6%, 0-6 months: 11.0%, >6 months: 7.3%;
      p = 0.012). Overall, our findings support the hypothesis that duration of
      breastfeeding is associated with fewer reported acute illnesses at 6 months of
      age and diarrheal illness and/or constipation episodes at 6, 12, and 24 months.
      Additionally, results from our study suggest a protective effect of breastfeeding
      from childhood overweight/obesity, as children who received breastmilk for 6
      months or longer had lower odds of overweight/obesity at age 3 years.

PMID- 30287330
TI  - Reduction in purchases of energy-dense nutrient-poor foods in Mexico associated
      with the introduction of a tax in 2014.
AB  - In 2014, an 8% tax on energy-dense nutrient-poor foods was implemented in Mexico
      with the aim of reducing its consumption. This paper estimated changes in
      household purchases of taxed food. We used the latest five waves of the
      nationally representative Mexican Income and Expenditure Survey (2008, 2010,
      2012, 2014 and 2016). The analytic sample comprises 154,777 households. We
      estimated changes in purchases based on a before and after comparison. Results
      show a reduction in purchases of taxed food of -5.4 g/week per capita, equivalent
      to a relative reduction of -5.3% in the 2014 and 2016 waves compared to the 2008,
      2010 and 2012 rounds. The largest relative reductions were in urban areas (
      6.9%), among households with children (-7.0%), households where the head had an
      intermediate educational level (-9.9%) and the southern region (-14.8%). We did
      not find a significant reduction in rural areas. While there is a large
      heterogeneity, the fiscal instrument has been effective in reducing taxed food
      purchases and has generated substantial revenue that could be used to finance
      policies for the prevention and treatment of obesity.

PMID- 30287331
TI  - Indicated preventive interventions for depression in children and adolescents: A
      meta-analysis and meta-regression.
AB  - Depression contributes about 2% to the global burden of disease. A first onset of
      depressive disorder or subsyndromal depressive symptoms is common in adolescence,
      indicating that early prevention is a priority. However, trials of preventive
      interventions for depression in youths show conflicting results. This systematic
      review and meta-analysis investigated the effectiveness of group-based cognitive
      behavioral therapy (GB-CBT) as a preventive intervention targeting subsyndromal
      depression in children and adolescents. In addition, the impact of different
      covariates (type of comparator and use of booster sessions) was assessed.
      Relevant articles were identified from previous systematic reviews, and
      supplemented with an electronic search spanning from 01/09/2014 to 28/02/2018.
      The retrieved articles were assessed for eligibility and risk of bias. Relevant
      data were extracted. Intervention effectiveness was pooled using a random-effects
      model and the impact of covariates assessed using meta-regression. 38 eligible
      articles (34 trials) were obtained. The analysis showed GB-CBT to significantly
      reduce the incidence (relative risk 0.43, 95% CI 0.21-0.87) and symptoms (Cohen's
      d -0.22, 95% CI -0.32 to -0.11) of depression at post-test compared to all
      controls. Comparisons with passive comparators suggested that the effect decayed
      over time. However, compared to active controls, a significant intervention
      effect was evident only after 12 month or more. Our results suggest that the
      preventive effect of GB-CBT wears off, but still lasts longer than the effect of
      active comparators. Only a few studies included booster sessions, precluding firm
      conclusions. Future studies should clarify to what extent maintenance strategies
      can prolong the preventive effect of GB-CBT.

PMID- 30287332
TI  - RIFM fragrance ingredient safety assessment, 2-formyl-6,6
      dimethylbicyclo(3.1.1)hept-2-ene, CAS Registry Number 564-94-3.

PMID- 30287333
TI  - RIFM fragrance ingredient safety assessment, 3-methyl-5-phenylpentanenitrile, CAS
      Registry Number 54089-83-7.

PMID- 30287334
TI  - RIFM fragrance ingredient safety assessment, acetal, CAS Registry Number 105-57
      7.

PMID- 30287335
TI  - RIFM fragrance ingredient safety assessment, ethyl 2-methyl-1,3-dioxolane-2
      acetate, CAS Registry Number 6413-10-1.
AB  - Ethyl 2-methyl-1,3-dioxolane-2-acetate (CAS # 6413-10-1) was evaluated for
      genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory
      toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental
      safety. Data show that ethyl 2-methyl-1,3-dioxolane-2-acetate is not genotoxic.
      Data from ethyl 2-methyl-1,3-dioxolane-2-acetate show that there are no safety
      concerns for skin sensitization under the current, declared levels of use. Data
      on ethyl 2-methyl-1,3-dioxolane-2-acetate provide a calculated MOE >100 for the
      repeated dose, developmental, and reproductive toxicity endpoints. The local
      respiratory toxicity endpoints were evaluated using the TTC for a Cramer Class
      III material, and the exposure to ethyl 2-methyl-1,3-dioxolane-2-acetate is below
      the TTC (0.47 mg/day). The phototoxicity/photoallergenicity endpoints were
      evaluated based on UV spectra; ethyl 2-methyl-1,3-dioxolane-2-acetate is not
      expected to be phototoxic/photoallergenic. For the environmental endpoints, ethyl
      2-methyl-1,3-dioxolane-2-acetate is not PBT as per the IFRA Environmental
      Standards, and its risk quotients (i.e., PEC/PNEC) for the aquatic environment
      based on its current volume of use in Europe and North America are <1.

PMID- 30287336
TI  - RIFM fragrance ingredient safety assessment, isobutyl butyrate, CAS Registry
      Number 539-90-2.

PMID- 30287337
TI  - RIFM fragrance ingredient safety assessment, 1,2,3,4,4a,7,8,8a-octahydro
      2,4a,5,8a-tetramethyl-1-naphthyl formate, CAS Registry Number 65405-72-3.

PMID- 30287338
TI  - Ochratoxin A induces cytoprotective autophagy via blocking AKT/mTOR signaling
      pathway in PK-15 cells.
AB  - Ochratoxin A (OTA) could cause a variety of toxicological effects especially
      nephrotoxicity in animals and humans. Autophagy is a highly conserved metabolic
      process that plays an important role in the maintenance of cellular homeostasis
      under stress. However, the role of autophagy in OTA-induced nephrotoxicity is
      unknown. In the present study, we demonstrated that OTA treatment at 2.0-8.0 MUM
      could increase cytotoxicity of PK-15 cells by inducing apoptosis as shown by the
      increased Annexin V/PI staining, increased caspase-3 and PARP cleavage and
      increased apoptotic nuclei. Meantime, autophagy was triggered when OTA was
      administrated, as indicated by markedly increased expressions of LC3-II, ATG5 and
      Beclin-1, accumulation of GFP-LC3 dots and increased double- or single-membrane
      vesicles. OTA treatment decreased p-AKT and p-mTOR activities, and OTA-induced
      autophagy was inhibited when insulin was applied. Furthermore, OTA treatments
      with autophagy inhibitors (3-methyladenine or chloroquine) or knockdown of
      autophagy-related genes (ATG5 or Beclin-1) resulted in significantly reduced
      autophagy level and enhanced cytotoxicity. In conclusion, OTA induces
      cytoprotective autophagy against its cytotoxicity and inactivation of AKT/mTOR
      axis plays a critical role in autophagy induction.

PMID- 30287339
TI  - Loss of hepatocyte beta-catenin protects mice from experimental porphyria
      associated liver injury.
AB  - BACKGROUND & AIMS: Porphyrias result from anomalies of heme biosynthetic enzymes
      and can lead to cirrhosis and hepatocellular cancer. In mice, these diseases can
      be modeled by administration of a diet containing 3,5-diethoxycarbonyl-1,4
      dihydrocollidine (DDC), which causes accumulation of porphyrin intermediates,
      resulting in hepatobiliary injury. Wnt/beta-catenin signaling has been shown to
      be a modulatable target in models of biliary injury; thus, we investigated its
      role in DDC-driven injury. METHODS: beta-Catenin (Ctnnb1) knockout (KO) mice, Wnt
      co-receptor KO mice, and littermate controls were fed a DDC diet for 2 weeks.
      beta-Catenin was exogenously inhibited in hepatocytes by administering beta
      catenin dicer-substrate RNA (DsiRNA), conjugated to a lipid nanoparticle, to mice
      after DDC diet and then weekly for 4 weeks. In all experiments, serum and livers
      were collected; livers were analyzed by histology, western blotting, and real
      time PCR. Porphyrin was measured by fluorescence, quantification of polarized
      light images, and liquid chromatography-mass spectrometry. RESULTS: DDC-fed mice
      lacking beta-catenin or Wnt signaling had decreased liver injury compared to
      controls. Exogenous mice that underwent beta-catenin suppression by DsiRNA during
      DDC feeding also showed less injury compared to control mice receiving lipid
      nanoparticles. Control livers contained extensive porphyrin deposits which were
      largely absent in mice lacking beta-catenin signaling. Notably, we identified a
      network of key heme biosynthesis enzymes that are suppressed in the absence of
      beta-catenin, preventing accumulation of toxic protoporphyrins. Additionally,
      mice lacking beta-catenin exhibited fewer protein aggregates, improved
      proteasomal activity, and reduced induction of autophagy, all contributing to
      protection from injury. CONCLUSIONS: beta-Catenin inhibition, through its
      pleiotropic effects on metabolism, cell stress, and autophagy, represents a novel
      therapeutic approach for patients with porphyria. LAY SUMMARY: Porphyrias are
      disorders resulting from abnormalities in the steps that lead to heme production,
      which cause build-up of toxic by-products called porphyrins. Liver is commonly
      either a source or a target of excess porphyrins, and complications can range
      from minor abnormalities to liver failure. In this report, we inhibited Wnt/beta
      catenin signaling in an experimental model of porphyria, which resulted in
      decreased liver injury. Targeting beta-catenin affected multiple components of
      the heme biosynthesis pathway, thus preventing build-up of porphyrin
      intermediates. Our study suggests that drugs inhibiting beta-catenin activity
      could reduce the amount of porphyrin accumulation and help alleviate symptoms in
      patients with porphyria.

PMID- 30287341
TI  - Healthcare resource utilization and costs by disease severity in an insured
      national sample of US patients with chronic hepatitis B.
AB  - BACKGROUND & AIMS: Chronic hepatitis B (CHB) affects over 2 million people in the
      US, with little reported on healthcare utilization and cost. We aimed to quantify
      annual CHB utilization and costs by disease severity and payer type. METHODS:
      Using Commercial, Medicare, and Medicaid databases from 2004 to 2015 and ICD9
      codes, we retrospectively identified adults with CHB, analyzing all-cause
      inpatient, outpatient, and pharmaceutical utilization and costs by disease
      severity. We compared healthcare utilization and costs between patients with CHB,
      without advanced liver disease, and matched non-CHB controls. All-cause
      inpatient, outpatient, and pharmaceutical utilization and costs were reported for
      each year and adjusted to 2015 dollars. RESULTS: Our sample consisted of 33,904
      CHB cases and 86,072 non-CHB controls. All-cause inpatient admissions (average
      stay 6-10 days) were more frequent in advanced liver disease states. Across all
      payers, patients with decompensated cirrhosis had the highest emergency
      department utilization (1.6-2.8 annual visits) and highest mean annual costs. The
      largest all-cause cost components for Commercial and Medicaid were inpatient
      costs for all advanced liver disease groups (Commercial: 62%, 47%, 68%; Medicaid:
      81%, 72%, 74%, respectively), and decompensated cirrhosis and hepatocellular
      carcinoma groups for Medicare (Medicare 49% and 48%). In addition, patients with
      compensated liver disease incurred costs 3 times higher than non-CHB controls.
      CONCLUSION: Patients with CHB, regardless of payer, who experienced decompensated
      cirrhosis, hepatocellular carcinoma, or a liver transplant incurred the highest
      annual costs and utilization of healthcare resources, but even patients with CHB
      and compensated liver disease incurred higher costs than those without CHB. All
      stakeholders in disease management need to combine efforts to prevent infection
      and advanced liver disease through improved vaccination rates, earlier diagnosis,
      and treatment. LAY SUMMARY: Hepatitis B virus can be a progressive disease
      leading to cirrhosis, hepatocellular carcinoma, liver transplant, and death.
      These progressive disease states are associated with a higher rate of
      hospitalizations, emergency room visits, outpatient visits, and costs compared to
      similar patients without hepatitis B. The most ill patients have the highest
      costs, but even patients who are less sick experience higher costs than patients
      without hepatitis B.

PMID- 30287340
TI  - Ketoconazole exacerbates mitophagy to induce apoptosis by downregulating
      cyclooxygenase-2 in hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a common cancer worldwide
      and remains a major clinical challenge. Ketoconazole, a traditional antifungal
      agent, has attracted considerable attention as a therapeutic option for cancer
      treatment. However, its mechanism of action is still not clearly defined. We
      aimed to evaluate the effect of ketoconazole on HCC and investigate the
      underlying mechanisms. METHODS: We examined the antitumor effect of ketoconazole
      on HCC cells, cell line-derived xenografts, and a patient-derived xenograft (PDX)
      model. Ketoconazole-induced mitophagy was quantified by immunofluorescence,
      immunoblotting and transmission electron microscopy analysis. We used mitophagy
      inhibitors to study the role of mitophagy on HCC cell death induced by
      ketoconazole. The role of cyclooxygenase-2 (COX-2 [encoded by PTGS2]) on
      ketoconazole-induced mitophagy was evaluated using gain- and loss-of-function
      methods. The synergistic effect of ketoconazole with sorafenib on HCC was
      measured in vivo and in vitro. RESULTS: Ketoconazole stimulated apoptosis in HCC
      cells by triggering mitophagy in vitro and in vivo. Mechanistically, ketoconazole
      downregulated COX-2, which led to PINK1 accumulation and subsequent mitochondrial
      translocation of Parkin (PRKN), and thereby promoted mitophagy-mediated
      mitochondrial dysfunction. Inhibiting mitophagy alleviated ketoconazole-induced
      mitochondrial dysfunction and apoptosis, supporting a causal role for mitophagy
      in the antitumor effect of ketoconazole. In the HCC PDX model, ketoconazole
      demonstrated a marked antitumor effect characterized by COX-2 downregulation,
      mitophagy activation, and apoptosis induction. Moreover, ketoconazole acted
      synergistically with sorafenib to suppress HCC xenograft growth in vivo.
      CONCLUSION: Our results demonstrate a novel link between ketoconazole and
      mitophagy machinery, providing preclinical proof of concept for the use of
      ketoconazole in HCC treatment. LAY SUMMARY: Hepatocellular carcinoma (HCC) is a
      common malignancy worldwide and remains a major clinical challenge. Our study
      reveals that ketoconazole, a broad-spectrum antifungal agent, activates
      PINK1/Parkin-mediated mitophagy by downregulating COX-2, consequently resulting
      in the acceleration of apoptosis and thereby inhibiting the growth of HCC.
      Furthermore, ketoconazole acts synergistically with sorafenib in the suppression
      of HCC growth in vitro and in vivo.

PMID- 30287342
TI  - Transcranial direct-current stimulation (tDCS) improves detection of simple
      bright stimuli by amblyopic Long Evans rats in the SLAG task and produces an
      increase of parvoalbumin labelled cells in visual cortices.
AB  - In this work visual functional improvement of amblyopic Long Evans rats treated
      with tDCS has been assessed using the "slow angled-descent forepaw grasping"
      (SLAG) test. This test is based on an innate response that does not requires any
      memory-learning component and has been used before for measuring visual function
      in rodents. The results obtained show that this procedure is useful to assess
      monocular but not binocular deficits, as controls and amblyopic animals showed
      significant differences during monocular but not during binocular assessment. On
      the other hand, parvoalbumin labelling was analysed in three areas of the visual
      cortex (V1M, V1B and V2L) before and after tDCS treatment. No changes in
      labelling were observed after monocular deprivation. However, tDCS treatment
      significantly improved vision through the amblyopic eye, and a significant
      increase of parvoalbumin-positive cells was observed in the three areas, both in
      the stimulated hemisphere but also in the non-stimulated hemisphere. This effect
      occurred both in control and amblyopic animals. Thus, tDCS induced changes are
      similar in controls and amblyopic animals, although only the last one showed a
      functional improvement.

PMID- 30287343
TI  - Oxidative stress in status epilepticus: a clinical-radiological correlation.
AB  - PURPOSE: To report oxidative stress in the patients with status epilepticus (SE),
      and correlate these with severity, MRI and outcome. METHODS: Thirty-five patients
      with SE and 34 controls were included. Blood sample was collected at admission
      for measuring superoxide dismutase (SOD), catalase, protein carbonyl,
      glutathione, total antioxidant capacity (TAC), malondialdehyde (MDA) and nitric
      oxide (NO). The type of SE, duration and Status Epilepticus Severity Score
      (STESS) at admission and refractoriness to treatment were noted. Cranial magnetic
      resonance imaging (MRI) findings, in-hospital deaths and disability at discharge
      were noted. RESULTS: The median age of the patients was 35 and 14 were females.
      The median STESS was 3 (0-5), and the score was unfavorable in 21(60%) patients.
      MRI was abnormal in 27(77%) patients. The patients with SE had significantly
      lower concentrations of SOD, catalase, protein carbonyl, GSH and TAC and higher
      concentrations of MDA and NO compared to the controls. These levels did not
      differ between refractory and non-refractory SE. Glutathione level inversely
      correlated with age. Malondialdehyde and NO levels positively correlated with age
      and inversely with GSH level. Five (14.3%) patients died in hospital. At
      discharge, 14 patients had good and 16 had poor outcome. The oxidative stress
      markers did not correlate with death or disability. CONCLUSION: Oxidative stress
      is increased in the patients with SE. Further study is needed in larger sample
      size to explore probable adjunctive treatment option.

PMID- 30287344
TI  - Hydrogen-rich saline protects rat from oxygen glucose deprivation and reperusion
      induced apoptosis through VDAC1 via Bcl-2.
AB  - BACKGROUND: Hydrogen is received as an inert gas that thought to be non
      functional in vivo previously. Recently, emerging evidences showed that in
      ischemia/reperfusion (IR) condition, hydrogen reduced cellular reactive oxygen
      species (ROS) production and ameliorated cell apoptosis. However, the underlying
      mechanism of hydrogen on IR-induced apoptosis remains elusive. Here we tried to
      unravel the mode of action of hydrogen with rat adrenal medulla cell line PC-12
      in vitro. METHODS: The mitochondrial functions before and after oxygen glucose
      deprivation and reperfusion (OGD/RP) were determined with corresponding dyes. The
      expression of Bcl-2, Bax, VDAC1, cytochrome c and caspase 9 was detected using
      Western Blotting method. Then Bcl-2 inhibitor, AB-199, was applied to investigate
      the role of Bcl-2 in OGD/RP-induced cell apoptosis. Finally, we manipulated the
      expression of VDAC1 with plasmids transfection to understand the effects of VDAC1
      on Bcl-2-mediated anti-apoptosis in OGD/RP. RESULTS: In this study, we
      demonstrated that hydrogen-rich saline (HRS) reduced OGD/RP-mediated neuronal
      loss by stimulating the expression of Bcl-2, which suppressed the activity of
      VDAC1. Consequently, hydrogen maintained the mitochondrial functions, restrains
      the release of cytochrome c and caspase 9 activation, resulting in ameliorated
      cell viability. CONCLUSIONS: HRS ameliorated OGD/RP-induced PC-12 cell apoptosis
      and provides a novel treatment option for ischemia.

PMID- 30287345
TI  - Coconut Oil Decreases Expression of Amyloid Precursor Protein (APP) and Secretion
      of Amyloid Peptides throughInhibitionof ADP-ribosylation factor 1 (ARF1).
AB  - : Alzheimer's disease (AD), affecting 5.3 million people in the U.S., impairs
      portions of the brain controlling memories. In humans, mutations in the amyloid
      precursor protein (APP) gene has been implicated in increased plaque formation,
      which can block the communication between nerve cells, decrease dendritic
      formation and increase cell death, and promote neuroinflammation. As coconut oil
      has been suggested to alleviate the symptoms in AD patients, we examined the
      impact of coconut oil on APP expression and secretion of amyloid peptides in N2a
      cells expressing the human APP gene (N2a/APP695). We found that coconut oil
      treatment decreased APP expression in N2a cells and reduced the secretion of
      Amyloid Peptides Abeta40 and Abeta42. Moreover, coconut oil treatment promoted
      differentiation of N2a cells. Our data suggest that ADP-Ribosylation Factor 1
      (ARF1) may contribute to the effects of coconut oil on APP expression and
      secretion of Abeta. A high ARF1 expression was also detected in the primary
      neuronal cells from the mice overexpressing the Swedish mutant APP.
      Immunostaining results revealed that APP is co-localized with ARF1 in the Golgi
      Apparatus and this interaction is impaired after coconut oil treatment.
      Furthermore, knockdown of ARF-1 using siRNA decreased secretion of amyloid
      peptides, confirming the impact of ARF1 on the secretion of amyloid peptides.
      CONCLUSION: These results suggest that coconut oil decreases intracellular ARF1
      expression, thereby resulting in an inhibition of APP and amyloid beta secretion.
      This study reveals a novel mechanism for intracellular APP processing in neuronal
      cells.

PMID- 30287346
TI  - Comparative analysis of spleen transcriptome detects differences in evolutionary
      adaptation of immune defense functions in bighead carp and silver carp.
AB  - The evolutionary divergence of the immune defense functions in bighead carp (A.
      nobilis) and silver carp (H. molitrix) is still not understood at the molecular
      level. Here, we obtained 48,821,754 and 55,054,480 clean reads from spleen tissue
      libraries prepared for bighead carp and silver carp using Illumina paired-end
      sequencing technology, respectively, and identified 4976 orthologous genes from
      the transcriptome data sets by comparative analysis. Adaptive evolutionary
      analysis showed that 212 orthologous genes and 255 Gene Ontology (GO) terms were
      subjected to positive selection(Ka/Ks values > 1) only in bighead carp, and 195
      orthologous genes and 309 GO terms only in silver carp. Among immune defense
      functions with significant evolutionary divergence, the positively selected
      biological processes in bighead carp mainly included B cell-mediated immunity,
      chemokine-mediated signaling pathway, and immunoglobulin mediated immune
      response, whereas those in silver carp mainly included the antigen processing and
      presentation, defense response to fungus, and detection of bacteria. Moreover, we
      found 2974 genes expressed only in spleen of bighead carp and 3494 genes
      expressed only in spleen of silver carp, where these genes were mostly enriched
      in the same biological processes or pathways. These results provide a better
      understanding of the differences in resistance to some diseases by bighead carp
      and silver carp, and also facilitate the identification of candidate genes
      related to disease resistance.

PMID- 30287347
TI  - Identification, characterisation and preliminary functional analysis of IRAK-M in
      grass carp (Ctenopharyngodon idella).
AB  - Interleukin-1 receptor-associated kinase (IRAK) family members play important
      roles in myeloid differentiation primary response 88 (MyD88)-dependent toll-like
      receptor (TLR) signaling, the crucial innate immune pathway in vertebrates. In
      the present study, the IRAK family gene IRAK-M (also called IRAK3) from grass
      carp (Ctenopharyngodon idella) was cloned and characterised. IRAK-M was mainly
      enriched in the spleen, and the significantly altered expression was observed
      after grass carp reovirus (GCRV) infection. Subcellular localisation showed that
      IRAK-M protein distributed uniformly in the entire cell and co-localised with
      MyD88 in the cytoplasm of transfected cells. Additionally, the interaction
      between IRAK-M and MyD88 was confirmed by bimolecular fluorescence
      complementation (BiFC) system. Moreover, deficient of IRAK-M in C. idella kidney
      cell line (CIK) with small interference RNA (siRNA) upregulated
      polyinosinic:polycytidylic acid (poly(I:C))-induced inflammatory cytokines
      production, including interleukin 8 (IL-8), IL-6, and tumour necrosis factor
      alpha (TNF-alpha), which reveals that IRAK-M functions as a negative regulator of
      inflammatory cytokines. Taken together, our results demonstrate that IRAK-M gene
      plays an important role in innate immune regulation and provide new insights into
      understanding the functional characteristics of the IRAK-M in teleosts.

PMID- 30287348
TI  - Characterization of four C1q/TNF-related proteins (CTRPs) from red-lip mullet
      (Liza haematocheila) and their transcriptional modulation in response to
      bacterial and pathogen-associated molecular pattern stimuli.
AB  - The structural and evolutionary linkage between tumor necrosis factor (TNF) and
      the globular C1q (gC1q) domain defines the C1q and TNF-related proteins (CTRPs),
      which are involved in diverse functions such as immune defense, inflammation,
      apoptosis, autoimmunity, and cell differentiation. In this study, red-lip mullet
      (Liza haematocheila) CTRP4-like (MuCTRP4-like), CTRP5 (MuCTRP5), CTRP6 (MuCTRP6),
      and CTRP7 (MuCTRP7) were identified from the red-lip mullet transcriptome
      database and molecularly characterized. According to in silico analysis, coding
      sequences of MuCTRP4-like, MuCTRP5, MuCTRP6, and MuCTRP7 consisted of 1128, 753,
      729, and 888 bp open reading frames (ORF), respectively and encoded 375, 250,
      242, and 295 amino acids, respectively. All CTRPs possessed a putative C1q
      domain. Additionally, MuCTRP5, MuCTRP6, and MuCTRP7 consisted of a collagen
      region. Phylogenetic analysis exemplified that MuCTRPs were distinctly clustered
      with the respective CTRP orthologs. Tissue-specific expression analysis
      demonstrated that MuCTRP4-like was mostly expressed in the blood and intestine.
      Moreover, MuCTRP6 was highly expressed in the blood, whereas MuCTRP5 and MuCTRP7
      were predominantly expressed in the muscle and stomach, respectively. According
      to the temporal expression in blood, all MuCTRPs exhibited significant
      modulations in response to polyinosinic:polycytidylic acid (poly I:C) and
      Lactococcus garvieae (L. garvieae). MuCTRP4-like, MuCTRP5, and MuCTRP6 showed
      significant upregulation in response to lipopolysaccharides (LPS). The results of
      this study suggest the potential involvement of Mullet CTRPs in post-immune
      responses.

PMID- 30287349
TI  - Periscapular muscle ultrasound as a diagnostic aid in scapular winging secondary
      to long thoracic nerve lesion. Comment on "Magnetic resonance imaging of dynamic
      scapular winging secondary to a lesion of the long thoracic nerve" by Nguyen et
      al. and on "A case of traumatic long thoracic nerve suffering: High-frequency
      ultrasound finding" by Coraci et al.

PMID- 30287350
TI  - French recommendations for osteoporosis prevention and treatment in patients with
      prostate cancer treated by androgen deprivation.
AB  - Androgen-deprivation therapy (ADT) in patients with prostate cancer can be
      achieved surgically or chemically, notably by prescribing LHRH analogs. Major
      bone loss occurs rapidly in both cases, due to the decrease in testosterone
      levels, and can increase the fracture risk. The objective of developing these
      recommendations was to achieve a practical consensus among various scientific
      societies, based on a literature review, about osteoporosis prevention and
      treatment in patients on ADT. The following scientific societies contributed to
      the work: Societe francaise de rhumatologie (SFR), Groupe de recherche et
      d'information sur les osteoporoses (GRIO), Groupe europeen d'etudes des
      metastases osseuses (GEMO), Association francophone pour les soins de support
      (AFSOS), Association francaise d'urologie (AFU), Societe francaise de
      radiotherapie oncologique (SFRO). Medication prescription and reimbursement
      modalities in France were taken into account. The recommendations state that a
      fracture-risk evaluation and interventions targeting risk factors for fractures
      should be provided to all patients on ADT. Those patients with a history of
      severe osteoporotic fracture and/or a T-score < -2.5 should receive osteoporosis
      therapy. Patients whose T-score is between -1.5 and -2.5 should be treated if
      they exhibit at least two other risk factors among the following: age >= 75
      years, history of non-severe fracture after 50 years of age, body mass index < 19
      kg/m2, at least three comorbidities (e.g., cardiovascular disease, depression,
      Parkinson's disease, and dementia), current glucocorticoid therapy, and repeated
      falls. When the decision is difficult, FRAX(r) score determination and an
      assessment by a bone disease specialist may be helpful. When osteoporosis therapy
      is not indicated, general measures should be applied, and bone mineral density
      measured again after 12-24 months. The anti-tumor effects of bisphosphonates and
      denosumab fall outside the scope of these recommendations.

PMID- 30287351
TI  - 2012 American guidelines for the management of gout as seen by general
      practitioners. Comment on "GOSPEL 3: Management of gout by primary-care
      physicians and office-based rheumatologists in France in the early 21st century -
      comparison with 2006 EULAR Recommendations." by Goossens et al.

PMID- 30287352
TI  - Rapid and efficient protocol to introduce exogenous DNA in Vibrio harveyi and
      Pseudoalteromonas sp.
AB  - Vibrio campbellii BAA-1116 is renowned for its bioluminescence properties, and
      genetic tools are available to genetically track this strain. However, many other
      ecologically important V. harveyi strains exist, for which only few genetic tools
      are available. In this study, a rapid electroporation protocol was developed to
      transform replicative plasmids in various environmental V. harveyi and
      Pseudoalteromonas strains. Moreover, a mini-Tn7 delivery system was modified to
      site-specifically integrate mini-transposons in the genome of V. harveyi ORM4. As
      a proof-of-principle, replicative plasmids carrying bioreporters were introduced
      by electroporation in V. harveyi ORM4 cells, and gene expression was followed at
      the single cell level. We could demonstrate that a flagellar gene is subjected to
      bimodal gene expression in V. harveyi ORM4, being highly expressed in 10% of the
      population in stationary phase. This study extends the possibilities to study
      environmental Vibrio strains and uncovers the occurrence of phenotypic
      heterogeneity in flagellar expression in Vibrio.

PMID- 30287353
TI  - Over expression of the constitutive expression refractory Mycobacterium
      tuberculosis Rv3488 protein with an acid-inducible expression system.
AB  - As inducible protein expression plasmids available for mycobacterial species are
      limited, here we demonstrate the utility of an acid-inducible promoter driving
      gene and subsequent protein expression of a difficult to express protein. We
      wanted to assess the use of an acid inducible promoter expression system to
      produce proteins in a mycobacterial system, specifically proteins that when
      overexpressed interfere with mycobacterial cell growth. Overexpression of those
      types of proteins would require a tightly regulated promoter system. We employed
      the Mycobacterium tuberculosis lipF minimal acid-inducible promoter (mpr) which
      had previously been shown to be upregulated by acidic stress >100 X and to have a
      low basal level of expression in the absence of acidic stress. It is active from
      pH 4.3 up to pH 6.4 making this an acid range that is compatible with
      mycobacterial growth or survival and active at acidic ranges encountered in vivo
      within acidified phagosomes of macrophages. We therefore cloned the M.
      tuberculosis gene Rv3488, whose product had been unable to be expressed
      constitutively, into a plasmid downstream of the lipF mpr promoter and
      overexpressed this gene in the presence of acidic pH in Mycobacterium smegmatis.
      Sustained overexpression of the gene leads to inhibition of replication of
      mycobacterial cells as well as inhibition of carotenoid pigment synthesis, while
      short-term overexpression leads to appropriate protein expression.

PMID- 30287354
TI  - Practical considerations for sampling and data analysis in contemporary
      metagenomics-based environmental studies.
AB  - Recent advancements in metagenomic-based studies, especially analyses of amplicon
      based DNA sequencing targeting taxonomic marker genes, has led to an
      unprecedented characterization of microbial communities from diverse ecosystems
      around the world. While originally constrained by a lack of appropriate
      analytical tools and sequencing depth, new technologies and computational and
      statistical algorithms have been developed to handle highly dimensional, next
      generation sequencing datasets. Both these tools allow for the robust analysis of
      structural and distributional patterns of microbiota essential for the
      understanding of microbial ecology and biogeography. Furthermore, consortia of
      individual laboratories working on large interdisciplinary research programs,
      like the Human and Earth Microbiome Projects, have developed standardized
      protocols for DNA extraction, sequencing pipelines, and bioinformatics. These
      approaches provide large repositories of publicly available data to serve as
      references for on-going and future, hypothesis-driven studies to better
      characterize the roles of microbial communities in diverse ecosystems. In this
      review, we outline the currently available statistical approaches and tools to
      aid in statistically powered study designs and analyses. Given what is now known
      about the enormous diversity and variability of the microbial communities in
      aquatic and terrestrial habitats, we also discuss practical considerations for
      sample collection. Due to the extensive advances made in the field of
      metagenomics over the last decade, rigorous, well replicated, hypothesis-driven
      studies are: 1) needed, 2) now possible, and 3) essential to make best use of
      sequencing-based technologies to characterize the roles of microbial communities
      in the structure and function of diverse ecosystems.

PMID- 30287355
TI  - A comparison of the ability of the National Early Warning Score and the National
      Early Warning Score 2 to identify patients at risk of in-hospital mortality: A
      multi-centre database study.
AB  - AIMS: To compare the ability of the National Early Warning Score (NEWS) and the
      National Early Warning Score 2 (NEWS2) to identify patients at risk of in
      hospital mortality and other adverse outcomes. METHODS: We undertook a multi
      centre retrospective observational study at five acute hospitals from two UK NHS
      Trusts. Data were obtained from completed adult admissions who were not fit
      enough to be discharged alive on the day of admission. Diagnostic coding and
      oxygen prescriptions were used to identify patients with type II respiratory
      failure (T2RF). The primary outcome was in-hospital mortality within 24 h of a
      vital signs observation. Secondary outcomes included unanticipated intensive care
      unit admission or cardiac arrest within 24 h of a vital signs observation.
      Discrimination was assessed using the c-statistic. RESULTS: Among 251,266 adult
      admissions, 48,898 were identified to be at risk of T2RF by diagnostic coding. In
      this group, NEWS2 showed statistically significant lower discrimination (c
      statistic, 95% CI) for identifying in-hospital mortality within 24 h (0.860,
      0.857-0.864) than NEWS (0.881, 0.878-0.884). For 1394 admissions with documented
      T2RF, discrimination was similar for both systems: NEWS2 (0.841, 0.827-0.855),
      NEWS (0.862, 0.848-0.875). For all secondary endpoints, NEWS2 showed no
      improvements in discrimination. CONCLUSIONS: NEWS2 modifications to NEWS do not
      improve discrimination of adverse outcomes in patients with documented T2RF and
      decrease discrimination in patients at risk of T2RF. Further evaluation of the
      relationship between SpO2 values, oxygen therapy and risk should be investigated
      further before wide-scale adoption of NEWS2.

PMID- 30287356
TI  - Donor IL-6 deficiency evidently reduces memory T cell responses in sensitized
      transplant recipients.
AB  - BACKGROUND: Resistance of tolerance induction in sensitized transplantation is
      mainly caused by generation of memory T cells. It is unknown whether alteration
      of graft niche such as level of pro-inflammatory cytokines can affect generation
      of memory T cells. METHODS: IL-6 deficient or wild-type (WT) C57BL/6 heart grafts
      were transplanted into pre-sensitized wild-type BALB/c recipients. Frequencies of
      memory T cells in the peripheral blood, grafts, and spleen were evaluated.
      RESULTS: We revealed that deficiency of donor IL-6 could significant prolong
      sensitized allograft survival. Compared with counterpart of WT group, frequency
      of effector memory CD4 + T cells (CD4 + CD44 + CD62L-) in the peripheral blood
      was significantly lower in the IL-6 KO group (p = .026) at day 3 post
      transplantation. Frequency of effector memory CD8 + T cells (CD8 + CD44 + CD62L-)
      in the peripheral blood was significantly lower in the IL-6 KO group (p < .0001)
      at day 3 post-transplant in comparison to that of WT group. No significant
      difference of central memory T cells was found between these groups. Histology
      demonstrated that deficiency of donor pro-inflammatory cytokine IL-6 (IL-6 KO
      group) preserved cardiac architecture with a mild infiltration of lymphocytes,
      whereas wild-type donor (control group) caused an evident lymphocytic
      infiltration within myocardial fibers of grafts and destruction of cardiac
      structure. CONCLUSION: Deficiency of pro-inflammatory IL-6 of donor graft could
      effectively prolong sensitized allograft survival, which was caused by a
      remarkable decrease of peripheral memory T cells rather than central memory T
      cells. This unveiled mechanism of targeting IL-6 signaling pathway might provide
      a novel insight into preventing allograft rejection for sensitized transplant
      recipients.

PMID- 30287357
TI  - Mechanical behaviors of tension and relaxation of tongue and soft palate:
      Experimental and analytical modeling.
AB  - This study is to characterize mechanical properties of uniaxial tension and
      stress relaxation responses of muscle tissues of tongue and soft palate. Uniaxial
      tension test and stress relaxation test on 39 fresh tissue samples from four five
      month-old boars (65 +/- 15 kg) are conducted. Firstly, the rationality of the
      samples' dimension design and experimenal data measurement is validated by one
      way ANOVA F-type test. Mechanical properties, including stress-strain
      relationship and stress relaxation characteristic, are then investigated in
      details to show the nonlinear behaviors of the tissue samples clearly. Finally, a
      constitutive model of representing the mechanical properties is formulated within
      the nonlinear integral representation framework proposed by Pinkin and Rogers,
      and corresponding material parameters are fitted to the experimental data based
      on the Levenberg-Marquardt minimization algorithm. The results of the fitting
      comparison prove that the formulated constitutive model can capture the observed
      nonlinear behaviors of the muscle tissue samples in both the axial tension and
      stress relaxation experiments.

PMID- 30287358
TI  - Carbon Fiducial Image Guidance Increases the Accuracy of Lumpectomy Cavity
      Localization in Radiation Therapy for Breast Cancer.
AB  - PURPOSE: We investigated the feasibility and accuracy of using carbon fiducials
      to localize the lumpectomy cavity with 2-dimensional kV imaging for early stage
      breast cancer radiation therapy. METHODS AND MATERIALS: Carbon fiducials were
      placed intraoperatively in the periphery of the lumpectomy cavity. Nine patients
      received whole breast irradiation with a boost, and 2 patients received 3
      dimensional conformal partial breast irradiation. A total of 89 fractions were
      assessed for setup errors relative to a predefined gold standard, cone beam
      computed tomography (CBCT) match to the lumpectomy cavity, using the following 4
      setup methods: (1) Align skin tattoos with lasers; (2) match bone with 2
      dimensional-2-dimensional (2D/2D) kV onboard imaging (OBI); (3) match the whole
      breast with CBCT; and (4) match carbon fiducials with 2D/2D kV OBI. The margin
      for the planning target volume (PTV) was calculated by 2 standard deviations of
      the setup errors, and compared among the 4 setup methods. Setup errors for
      patients treated with free breathing and patients with deep inspiration breath
      hold were also compared. RESULTS: The carbon fiducials were sufficiently visible
      on OBI for matching and introduced minimal artifacts. Of the 4 alignment methods,
      2D/2D OBI match to fiducials resulted in the smallest setup errors. The PTV
      margin was 12 mm for aligning skin tattoos using lasers, 9.2 mm for matching bone
      on OBI, 6.5 mm for matching breast on CBCT, and 3.5 mm for matching fiducials on
      2D/2D OBI. Compared with free breathing, deep inspiration breath hold generally
      reduced the standard deviations of the setup errors, but further investigation
      would be needed. CONCLUSIONS: Matching to carbon fiducials increased the
      localization accuracy to the lumpectomy cavity. This reduces residual setup error
      and PTV margins, facilitating tissue sparing without diminishing treatment
      efficacy.

PMID- 30287359
TI  - Fabrication and in vitro characterization of HPMC-g-poly(AMPS) hydrogels loaded
      with loxoprofen sodium.
AB  - The aim of this study was to prepare hydroxypropyl-methyl cellulose (HPMC)-K15
      based hydrogels via free radical polymerization using 2-acrylamido-2-methyl
      propane sulphonic acid (AMPS) as a monomer and N,N'-methylene bisacrylamide
      (MBAAm) as a crosslinker. Loxoprofen sodium was chosen as a model drug and
      successfully loaded in hydrogel discs. Sol-gel, porosity, loading efficiency, and
      the in vitro drug release analysis were carried out to evaluate its drug delivery
      potential. HMPC-g-poly(AMPS) hydrogels were characterized by using Fourier
      transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC),
      and scanning electron microscopy (SEM) approaches. Maximum swelling and drug
      release were observed at pH 7.4. Kinetic modelling suggested that drug release
      followed first-order kinetics with the non-Fickian mechanism. FTIR and DSC
      confirmed the formation of new hydrogels. SEM micrographs confirmed uneven,
      rough, and partially porous type of surface. These results suggested that HMPC-g
      poly(AMPS) hydrogels can be a prospective pH-responsive carrier for delivery of
      water-soluble drugs, such as loxoprofen sodium.

PMID- 30287360
TI  - Comparison of the structural characterization and physicochemical properties of
      starches from seven purple sweet potato varieties cultivated in China.
AB  - In this study, the structural characterization and physicochemical properties of
      starches from seven purple sweet potato varieties (Fuzi No. 1, Guang No. 161,
      Jihei No. 1, Ningzi No. 1, Ningzi No. 2, Xuzi No. 6 and Xuzi No. 8) cultivated in
      China were compared. Starch granules of purple sweet potatoes all exhibited
      round, polygonal and hemispherical shapes with granule sizes ranging from 4.3 to
      23.6 MUm. X-ray powder diffraction patterns and 13C nuclear magnetic resonance
      spectra revealed purple sweet potato starches were CA-type with relative
      crystallinity varying from 34.0% to 37.3%. Small-angle X-ray scattering spectra
      indicated the lamellar repeat distances of starch granules were in the range of
      9.962-10.137 nm. Ratios of 1045/1022 cm-1 and 1022/995 cm-1 of Fourier transform
      infrared spectra varied in the range of 0.689-0.887 and 0.850-0.974,
      respectively. Amylose contents of purple sweet potato starches differed from 18.2
      to 27.2%. Purple sweet potato starches exhibited different gelatinization
      properties but similar thermal stability. Moreover, resistant starch contents
      varied from 29.25% to 43.50%. Our study indicated the granule size, relative
      crystallinity, the degree of short-range order, amylose content, gelatinization
      property and in vitro digestibility of purple sweet potato starches were greatly
      influenced by the variety of purple sweet potato.

PMID- 30287361
TI  - Hyaluronic acid, a promising skin rejuvenating biomedicine: A review of recent
      updates and pre-clinical and clinical investigations on cosmetic and
      nutricosmetic effects.
AB  - Hyaluronic acid (HA) plays multifaceted role in regulating the various biological
      processes such as skin repairmen, diagnosis of cancer, wound healing, tissue
      regeneration, anti-inflammatory, and immunomodulation. Owing to its remarkable
      biomedical and tissue regeneration potential, HA has been numerously employed as
      one of the imperative components of the cosmetic and nutricosmetic products. The
      present review aims to summarize and critically appraise recent developments and
      clinical investigations on cosmetic and nutricosmetic efficacy of HA for skin
      rejuvenation. A thorough analysis of the literature revealed that HA based
      formulations (i.e., gels, creams, intra-dermal filler injections, dermal fillers,
      facial fillers, autologous fat gels, lotion, serum, and implants, etc.) exhibit
      remarkable anti-wrinkle, anti-nasolabial fold, anti-aging, space-filling, and
      face rejuvenating properties. This has been achieved via soft tissue
      augmentation, improved skin hydration, collagen and elastin stimulation, and face
      volume restoration. HA, alone or in combination with lidocaine and other co
      agents, showed promising efficacy in skin tightness and elasticity, face
      rejuvenation, improving aesthetic scores, reducing the wrinkle scars, longevity,
      and tear trough rejuvenation. Our critical analysis evidenced that
      application/administration of HA exhibits outstanding nutricosmetic efficacy and
      thus is warranted to be used as a prime component of cosmetic products.

PMID- 30287362
TI  - Modified nickel ferrite nanocomposite/functionalized chitosan as a novel
      adsorbent for the removal of acidic dyes.
AB  - As a new type of magnetic adsorbent, a nickel ferrite nanocomposite modified by
      functionalized chitosan was developed to remove methyl orange and Congo red from
      aqueous solutions. This new adsorbent was characterized and utilizing batch
      adsorption approach, the mechanism of methyl orange and Congo red removal were
      probed. Following that the study on pertinent parameters which could influence
      the efficiency of the dyes removal, i.e. pH of the solution, initial dye
      concentration, dose of the adsorbent, and contact time were accomplished in order
      to arrive their optimized values by using response surface methodology. In
      addition, kinetics and isotherm studies were conducted on the developed system.
      Langmuir model was used to probe adsorption isotherm, acquiring adsorption
      capacity of 551.2 and 274.7 mg g-1 for methyl orange and Congo red, respectively.
      Both of methyl orange and Congo red adsorption kinetics obeyed a pseudo-second
      order kinetic model, indicating that adsorption was the rate-limiting step and
      only 5 min was required to remove 50% of dyes. The fitting of experimental data
      was fulfilled with intra-particle diffusion reaching to conclusion that the
      adsorption kinetic could be controlled simultaneously by film diffusion and intra
      particle diffusion. Furthermore, the desorption studies of dyes showed that the
      adsorbent is reusable.

PMID- 30287363
TI  - Extraction, preliminary characterization and in vitro antioxidant activity of
      polysaccharides from Oudemansiella radicata mushroom.
AB  - Oudemansiella radicata mushroom has many functions. Optimal condition of
      extracting its polysaccharides (ORP) with a yield of 5.85 +/- 0.13% were
      determined by using RSM: extraction temperature 84  degrees C, extraction time
      2.3 h and ratio of water to raw material 20.0 mL/g. ORP-1, ORP-2 and ORP-3 were
      further obtained by chromatography with an average molecular of 13,921 Da, 14,942
      Da and 10,209 Da, respectively. ORP-1 is mainly composed of mannose, ribose,
      glucose, galactose and xylose in a ratio of 2.46:2.63:3.89:3.22:2.78; ORP-2 is
      mainly composed of ribose, glucose and xylose in a ratio of 2.63:3.38:2.65; ORP-3
      is mainly composed of glucose, xylose in a ratio of 3.38: 2.65. ORP exhibits
      relatively strong in vitro antioxidant activity. Except crude ORP, ORP-1 has the
      highest DPPH and ABTS radical scavenging activity, and ORP-3 shows the strongest
      hydroxyl radical scavenging activity and ferrous ion chelating activity, while
      the three fractions have no significance in scavenging radical superoxide anion.

PMID- 30287364
TI  - RK, the first scorpion peptide with dual disintegrin activity on alpha1beta1 and
      alphavbeta3 integrins.
AB  - Scorpion peptides are well known for their pharmaceutical potential on different
      targets. These include mainly the ion channels which were found to be highly
      expressed in many diseases, including cancer, auto-immune pathologies and
      Alzheimer. So far, however, the disintegrin activity had only been characterized
      for snake venom molecules. Herein, we present the first short peptide, purified
      from the venom of Buthus occitanus tunetanus, (termed RK) able to inhibit the
      cell adhesion of Glioblastoma, Melanoma and Rat pheochromocytoma to different
      extracellular matrix (ECM) receptors. Anti-integrin antibody assay suggests that
      RK interacts with both alpha1beta1 and alphavbeta3 with a more pronounced effect
      for the former. The examination of the primary structure of RK suggests the
      involvement of two motifs: KSS, analogue to KTS which was characterized for
      alpha1beta1 Snake venom disintegrins, and ECD, analogue to RGD which was found to
      be active on alphavbeta3. To assess their roles in the disintegrin activity of
      RK, we conducted a computational analysis. The molecular docking study shows that
      RK involves mainly two segments to interact with the alpha1beta1 integrin, but
      the peptide does not implicate the KSS motif in the interaction. The molecular
      modeling study, suggests the key contribution of the ECD segment in the
      interaction with alphavbeta3 integrin.

PMID- 30287365
TI  - Preparation and characterization of WS2 decorated and immobilized on chitosan and
      polycaprolactone as biodegradable polymers nanofibers: Photocatalysis study and
      antibiotic-conjugated for antibacterial evaluation.
AB  - In the present work, WS2 nanoparticles and immobilized on chitosan and
      polycaprolactone as biodegradable polymers as photocatalyst were developed and
      studied for photocatalytic degradation of representative Neomycin as an
      aminoglycoside antibiotic. The WS2 nanoparticles were synthesized using the
      hydrothermal method. Further, the photocatalyst were characterized by different
      analytical instruments energy dispersive X-ray spectrometer (EDS), scanning
      electron microscopy (SEM), X-ray diffraction (XRD) analysis, and UV-Vis
      absorption spectroscopy, in order to understand their physical and optical
      properties. The mean crystallite sizes of WS2 nanoparticles, WS2/chitosan
      nanofibers and WS2/polycaprolactone nanofibers were 80.00, 70.14 and 68.71 nm,
      respectively. The optical absorption study revealed the presence of direct band
      to-band transition with band-gap ranging from 2.0 to 1.8 eV for WS2, WS2/chitosan
      nanofibers and WS2/polycaprolactone nanofibers, respectively. The photocatalytic
      activity of the three photocatalyst was tested by UV-light-induced degradation of
      Neomycin antibiotic. The WS2/chitosan nanofibers and WS2/polycaprolactone
      nanofibers photocatalyst showed high amount of photodegradation in comparison to
      WS2 nanoparticles. The optimum degradation using WS2, WS2/chitosan nanofibers and
      WS2/polycaprolactone nanofibers occurred under UV light at pH:7 in 40 min. The
      bactericidal test was determined under light illumination (visible source light)
      and that the neomycin conjugated WS2/chitosan nanofibers and WS2/polycaprolactone
      nanofibers demonstrated good efficiency in antibacterial efficiency compared to
      pure WS2/chitosan nanofibers and WS2/polycaprolactone nanofibers.

PMID- 30287366
TI  - Semi-interpenetrating hydrogels from carboxymethyl guar gum and gelatin for
      ciprofloxacin sustained release.
AB  - The present work reports the synthesis of new generation semi-interpenetrating (s
      IPN) hydrogels from carboxymethyl guar gum (CMGG) and gelatin with enhanced gel
      properties for suitable drug delivery applications. Hydrogels are three
      dimensional polymer networks which respond to water and ion interactions.
      Irreversible s-IPN hydrogels were prepared by CMGG interactions in gelatin and
      characterized in FT-IR, SEM and thermal studies. CMGG was synthesized by
      Hofmeister ion guided homogeneous phase reactions. The swelling kinetics of the
      newer s-IPN hydrogels followed Schott's pseudo second order model. Furthermore,
      the hydrogels were hemocompatible, non-cytotoxic and appropriate for applications
      in physiological environment. Model drug ciprofloxacin was loaded within the
      hydrogels and the drug release was found to be a combination of both diffusion
      and hydrogel degradation. New generation s-IPN biopolymer hydrogels of
      carboxymethyl guar gum and gelatin holds promise for its application as sustained
      drug delivery device or alternatively as hydrogel sorbents for bio-toxins and
      molecules of biomedical importance.

PMID- 30287367
TI  - Effects of temperature, starch concentration, and plasticizer concentration on
      the physical properties of ulluco (Ullucus tuberosus Caldas)-based edible films.
AB  - Ulluco starch could be a promising renewable source for the production of
      biodegradable or edible films, as an alternative to plastic. This would mitigate
      the negative impact of plastics on the environment. The aim of this work was to
      study the effect of the starch concentration (SC), glycerol concentration (GC),
      and drying temperature (T) of ulluco starch-based films on their physical
      properties using stepwise regression (SR) and artificial neural network (ANN)
      approaches. The physical properties, such as the solubility (S), water vapour
      permeability (WVP), tensile strength (TS), elongation at break (EB), and
      transparency, of the edible films were satisfactory. The feed-forward and cascade
      forward neural networks satisfactorily modelled the effect of the SC, GC, and T
      on the mechanical, optical, and water-affinity properties (WAP) of the edible
      films. ANN approach showed better results than SR in all the properties and ANN
      models were used in the sensitivity analysis and optimization. The global
      sensitivity analysis showed that the GC had the greatest influence on the
      physical properties. A desirability function-based optimization including WVP, EB
      and OP showed comparable values between experimental and estimated data. Based on
      the results of this study, the use of ulluco starch for the preparation of edible
      films has enormous potential for the replacement of non-biodegradable plastic
      packaging.

PMID- 30287368
TI  - Physicochemical analysis, structural elucidation and bioactivities of a high
      molecular-weight polysaccharide from Phellinus igniarius mycelia.
AB  - Phellinus igniarius is a well-known edible and medicinal fungus consumed in Asia
      for centuries. In the present study, a polysaccharide named PIP-1 was obtained
      from Phellinus igniarius mycelia, its physicochemical properties were determined,
      its detailed structures were elucidated by analysis of its depolymerized product,
      and its antioxidant and antitumor activities were evaluated. Results showed that
      PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear
      repeating backbone composed of glucopyranose (Glcp), galactopyranose, and
      mannopyranose joined by alpha-(1 -> 4), alpha-(1 -> 3), and alpha-(1 -> 6)
      linkages, and single alpha-terminal-D-Glcp as side chains 6-O-linked to the main
      chain according to the GC-MS and NMR results, and exhibited triple helical
      structure. Pharmacological results revealed that PIP-1 could effectively scavenge
      hydroxyl radicals, partly scavenge DPPH radials and chelate ferrous metal ions.
      Furthermore, PIP-1 showed potent inhibitory effects on growth of HT-29 and MCF-7
      cells. These findings suggested that high-molecular-weight PIP-1 containing
      triple helical structure and only alpha-type glycosidic bond holds promise as
      novel functional foods and agents to promote human health.

PMID- 30287369
TI  - Reactive oxygen species generation and human serum albumin damage induced by the
      combined effects of ultrasonic irradiation and brilliant cresyl blue.
AB  - In this paper, brilliant cresyl blue (BCB) was selected as a sonosensitizer. The
      sonodynamic damage to human serum albumin (HSA) in the presence of BCB and the
      mechanism were studied by means of fluorescence and absorption spectra. Firstly,
      BCB could quench the intrinsic fluorescence of HSA obviously and the quenching
      mechanism was static quenching due to the formation of HSA-BCB complex. The
      results of the displacement experiments and the molecular modeling suggested that
      the binding site of BCB on HSA was site I, and hydrophobic forces and hydrogen
      bonds played major roles in the interaction between HSA and BCB. Secondly, the
      damage of HSA induced by the combined effects of ultrasonic irradiation and BCB
      was more efficient than that only BCB or ultrasound irradiation, which confirmed
      that BCB had sonodynamic activity. The damage degree of HSA was positively
      correlated with reactive oxygen species (ROS) produced in the system, which
      indicated that ultrasound could activate BCB to produce ROS, and the kinds of ROS
      produced by the combined effects of ultrasonic irradiation and BCB were mainly
      hydroxyl free radical, singlet oxygen and superoxide anion radical.

PMID- 30287370
TI  - A biotechnological approach to immunotherapy: Antivenom against Crotalus durissus
      cascavella snake venom produced from biodegradable nanoparticles.
AB  - Snakebite envenoming is a tropical disease neglected worldwide. In Brazil, the
      Crotalus durissus cascavella (CDC) snake belongs to a genus with venom of highest
      lethality. A search for new immunoadjuvants aimed to expand the therapeutic
      alternatives to improve vaccines and antivenom. This approach proposed to produce
      small and narrow-sized cationic CDC venom-loaded chitosan nanoparticles (CHNP)
      able to induce antibody response against the CDC venom. The ionic gelation method
      induced the formation of stable and slightly smooth spherical nanoparticles (<160
      nm) with protein loading efficiency superior to 90%. The interactions between
      venom proteins and CHNP assessed using FT-IR spectroscopy corroborated with the
      in vitro release behavior of proteins from nanoparticles. Finally, the
      immunization animal model using BALB/c mice demonstrated the higher effectiveness
      of CDC venom-loaded CHNP compared to aluminum hydroxide, a conventional
      immunoadjuvant. Thus, CHNPs loaded with CDC venom exhibited a promising
      biotechnological approach to immunotherapy.

PMID- 30287371
TI  - Binding of anticancer drug daunomycin to parallel G-quadruplex DNA [d-(TTGGGGT)]4
      leads to thermal stabilization: A multispectroscopic investigation.
AB  - Guanine rich DNA sequences form four stranded G-quadruplex structures found in
      telomeric DNA and oncogene promoters. Small molecules binding and stabilizing the
      G-quadruplex disrupt telomere maintenance and gene regulation, thereby limiting
      the proliferation of cancer cells. The anti-cancer drug daunomycin binds to both
      G-quadruplex DNA and duplex DNA. We have undertaken a study of interaction of
      daunomycin to [d-(TTGGGGT)]4 comprising telomeric DNA sequence from Tetrahymena
      thermophilia to understand the mechanisms of its action. Absorbance, fluorescence
      and circular dicroism spectra show significant change on interaction with no
      change in wavelength maxima. The daunomycin dimers present in free state in
      solution are disrupted on binding. Presence of all sequential short inter proton
      distance contacts in nuclear magnetic resonance spectra confirm external binding.
      The observed inter molecular nuclear Overhauser enhancements, changes in chemical
      shift and molecular docking studies establish well defined binding of daunomycin
      at two different sites of G-quadruplex DNA. Thermal stabilization of [d
      (TTGGGGT)]4 by 10-15  degrees C upon daunomycin binding is expected to reduce
      access of telomerase to its functional site at telomeres. The present studies on
      mode of action pave the way for alternate derivatives/analogues by chemical
      modification of anthracyclines to arrive at a more potent telomerase inhibitor.

PMID- 30287372
TI  - Molecular cloning and characterization of the novel CYP2J2 in dromedary camels
      (Camelus dromedarius).
AB  - Although its economic, cultural and biological importance, many genes haven't
      been depicted, sequenced or analyzed to date for Camelus dromedarius. In the
      present paper, the full-length c-DNA of a novel CYP2J2 (GenBank accession number
      MH511989) was cloned from liver, heart, and kidney mRNA by RACE-PCR. The full
      length c-DNA of the cloned CYP2J2 was sequenced and analyzed using bioinformatics
      methods. The full-length c-DNA sequence was 2135 bp with no introns. The open
      reading frame (ORF) had 1341 nucleotides which coded for a putative protein of
      446 amino acids. The deduced protein is located in the endoplasmic reticulum. It
      has two transmembrane regions. The nucleotides and deduced amino acids sequences
      of the cloned CYP2J2 were 1400 nucleotides and 47 amino acids shorter than the
      predicted homolog respectively. This study is the first description of the
      putative CYP2J2 gene, which opens the way to a new investigation-so far-never
      accomplished in Camelus dromedarius.

PMID- 30287374
TI  - Increased expression of long non-coding RNA SNHG16 correlates with tumor
      progression and poor prognosis in non-small cell lung cancer.
AB  - In this study, we report that lncRNA SNHG16 is upregulated in non-small cell lung
      cancer (NSCLC) tissues, and correlates with tumor size, TNM stage and lymph node
      metastasis. Kaplan-Meier analysis shows that the patients with high SNHG16
      expression have poorer disease-free survival (DFS) and overall survival (OS) than
      the patients with low SNHG16 expression. Multivariate Cox regression analysis
      reveals that SNHG16 expression could be regarded as an independent predictor for
      DFS and OS in NSCLC patients. Cell experiments show that SNHG16 promotes NSCLC
      cell proliferation, migration and invasion. miR-146a is further identified and
      confirmed to be the target of SNHG16, and SNHG16 functions by targeting miR-146a.
      Subsequently, MUC5AC, a major mucin in the human respiratory tract correlated
      with post-operative metastasis and recurrence of NSCLC, is confirmed to be
      regulated by SNHG16 and miR-146a, and plays a positive role in promoting cell
      proliferation, migration and invasion, which might be involved in the oncogenic
      activity of SNHG16-miR-146a axis in NSCLC. Animal experiments also confirm these
      conclusions. Collectively, these results elucidate a potential mechanism
      underlying the carcinogenesis role of SNHG16 in NSCLC, and indicate that SNHG16
      could act as a novel promising marker for prognosis, and a potential therapeutic
      target for NSCLC treatment.

PMID- 30287373
TI  - Incorporation of magnetic NaX zeolite/DOX into the PLA/chitosan nanofibers for
      sustained release of doxorubicin against carcinoma cells death in vitro.
AB  - In the present study, the magnetic NaX nanozeolites were synthesized via
      microwave heating method and loaded into the PLA/chitosan solution. Doxorubicin
      (DOX) as an anticancer drug was simultaneously incorporated into the PLA/chitosan
      solution and the electrospinning process was used to fabricate the
      PLA/chitosan/NaX/Fe3O4/DOX nanofibers for sustained release of DOX against
      carcinoma cells death. The synthesized nanozeolites were characterized using X
      ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and
      energy dispersive X-ray spectroscopy (EDX) analysis. The scanning electron
      microscopy (SEM) was used to determine the morphology and fiber diameter
      distribution of synthesized nanofibers. The DOX loading efficiency and in vitro
      DOX release profiles from nanofibers were investigated. The kinetic models
      including zero-order, Higuchi and Korsmeyer-Peppas were used to analyze the
      release mechanism of DOX from nanofibers. The effect of ferrite nanoparticles on
      the DOX release from chitosan/PLA/NaX/DOX and chitosan/PLA/NaX/Fe3O4/DOX
      nanofibers have been investigated in the presence of magnetic field and without
      magnetic field. The antitumor activity of synthesized nanofibers was also
      investigated on the carcinoma cells death. The maximum killing percentage of
      H1355 cells was found to be 82% using DOX loaded chitosan/PLA/NaX/ferrite in the
      presence of external magnetic field after 7 days of treatment.

PMID- 30287375
TI  - Characterization of the complete mitochondrial genome of Simulium (Byssodon)
      maculatum (Diptera: Simuliidae) and its phylogenetic implications.
AB  - The mitochondrial (mt) genome of the black fly Simulium (Byssodon) maculatum, a
      pest of great importance for both humans and livestock, is sequenced and
      annotated for the first time. The genome structure, gene order and codon usage
      are typical among Diptera mt genomes. The mt genome is circular and 15,799 bp in
      length with 13 protein coding genes (PCGs), 22 transfer RNA genes (tRNAs), two
      ribosomal RNA genes (rRNAs) and a control region (CR), and with weakly positive
      AT-skew (0.02) and negative GC-skew (-0.12). Phylogenetic relationships of 16
      species representing five families of Culicomorpha and two outgroups, based on mt
      genome data, were analyzed using both Maximum Likelihood and Bayesian methods.
      The monophyly of Culicomorpha is well supported, while Chironomoidea is indicated
      as a paraphyletic group. The well supported monophyletic Simuliidae is the sister
      group to Culicidae.

PMID- 30287376
TI  - Optimization of the preparation conditions of thermo-sensitive chitosan hydrogel
      in heterogeneous reaction using response surface methodology.
AB  - A thermo-sensitive hydroxybutyl chitosan (HBC) hydrogel was prepared by using 1,2
      butene oxide as an etherification modifying agent. To obtain the maximum yield of
      HBC, response surface methodology (RSM) was applied to optimize its preparation
      conditions. Key factors were chosen firstly by Plackett-Burman design (PBD)
      experiments, such as the concentration of NaOH, the ratio of isopropanol to water
      and reaction temperature. Steepest ascent experiments were employed to reach the
      top region of the response and determine the appropriate levels of three key
      factors. A three-level-three-variable Box-Behnken design (BBD) was used to
      further optimize the synthesis parameters. The results indicated that when the
      concentration of NaOH and the ratio of isopropyl alcohol to water were 40.65% and
      2.68:1 at reaction temperature of 59  degrees C, respectively, the yield of HBC
      production was 5.897 +/- 0.112 g and close to the predicted value (6.002 g),
      which demonstrated that the effectiveness of BBD model and the controllability
      for the yield of HBC in the heterogeneous reaction system.

PMID- 30287377
TI  - Synthesis of a bio-based polyurethane/chitosan composite foam using ricinoleic
      acid for the adsorption of Food Red 17 dye.
AB  - A novel bio-based polyurethane/chitosan foam (PU/chitosan) was synthesized using
      a polyol derived from castor oil and applied to remove Food Red 17 dye (FR17)
      from aqueous solutions. PU/chitosan foam presented better characteristics and
      adsorption potential than polyurethane foam (PU). PU/chitosan foam showed a semi
      crystalline structure, with several functional groups, high porosity and good
      mechanical properties. These characteristics are adequate for adsorptive
      separations. Using identical adsorption conditions, PU/chitosan was able to
      remove >98% of FR17 dye from the solution, while, PU removed only 40%. The
      adsorption of FR17 on PU/chitosan composite foam was favored at pH 2. Pseudo
      second order model was the most adequate to represent the kinetic data. The
      equilibrium data followed the Sips model, with a maximum adsorption capacity of
      267.24 mg g-1. The adsorption process was spontaneous, favorable and endothermic.
      The results showed that polyurethane foams are capable to support chitosan,
      generating an adsorbent with better mechanical characteristics and high potential
      to remove anionic dyes from aqueous media.

PMID- 30287378
TI  - Solidification of liquid Modified Apple Polysaccharide by its adsorption on solid
      porous carriers through spray drying and evaluation of its potential as binding
      agent for tablets.
AB  - In the present study application of Modified Apple Polysaccharide (MAP) as tablet
      binder was evaluated. Liquid MAP was extracted from apple and solidified by
      adsorbing it on porous surface of Aerosil-200 and trehalose and this dispersion
      was dried using spray dryer. The concentration of excipients as well as spray
      drying conditions was optimised by using Box Behnken Design to achieve desirable
      powder characteristics. The optimised batch of solid MAP was characterized by
      DSC, PXRD, SEM, and FT-IR studies that confirmed complete adsorption of liquid
      MAP on the surface of Aerosil-200 and trehalose. This solid MAP was investigated
      for its binding efficacy for tablet formulation and its binding potential was
      compared with acacia and polyvinyl pyrrolidone K-30. Mesalamine (model drug)
      granules containing different concentration of binders were prepared by wet
      granulation. The granules were evaluated for micromeritic properties and results
      were found within the pharmacopoeial limits. The prepared tablets were subjected
      for post compression studies such as hardness, friability, disintegration,
      dissolution, physical stability, content uniformity and percentage elastic
      recovery and their results were found good. At 2.5% w/w concentration in tablet,
      the solid MAP has shown shorter disintegration time and faster dissolution
      profile as compared to other concentrations used including good physico
      mechanical properties.

PMID- 30287379
TI  - Relations between chain-length distribution, molecular size, and amylose content
      of rice starches.
AB  - Starch molecular structure, in terms of chain-length distribution (CLD) and
      molecular size, are important structural features regarding to "(starch)
      structure-property" relations for starch-based foods. In this study, amylopectin
      CLDs from fluorophore-assisted carbohydrate electrophoresis (FACE) are
      parameterized by a biosynthesis-based model, amylose CLDs and molecular sizes of
      amylose and amylopectin are measured by size-exclusion chromatography (SEC), and
      statistically meaningful relationships are established between starch CLDs,
      starch molecular size, and amylose content using rice starches with a wide range
      of amylose content. This shows that amylopectin molecular size is increased by
      increasing the proportion of short amylopectin chains with degree of
      polymerization (DP) 6-32 and decreasing the percentage of long amylopectin chains
      with DP 63-100. On the other hand, molecular sizes of both branched amylopectin
      and amylose molecules are negatively correlated with amylose content, suggesting
      that high-amylose rice tends to have smaller amylopectin and amylose molecular
      sizes. These relations are rationalized in terms of chain-length effects on the
      production of branched amylopectin and amylose molecules between different rice
      cultivars, which could provide new insights regarding to starch "structure
      property" relations.

PMID- 30287380
TI  - Glucose-sensitive delivery of metronidazole by using a photo-crosslinked chitosan
      hydrogel film to inhibit Porphyromonas gingivalis proliferation.
AB  - A novel glucose-sensitive drug delivery system with controlled release of
      metronidazole was synthesized by using biocompatible photo-crosslinked chitosan
      hydrogel film. Specifically, methacrylic anhydride, as photosensitive substance,
      was firstly grafted on chitosan molecular chains and then UV irradiation was
      applied as the crosslinking method. Glucose sensitivity was endowed by
      immobilizing glucose oxidase on the surface of chitosan film. The physicochemical
      characteristics including chemical composition, crosslinking degree, mechanical
      strength and related enzyme properties were investigated successively.
      Cytotoxicity test, drug release and anti-bacterial test were carried out,
      respectively. The results show that this photo-crosslinked hydrogel film has good
      mechanical properties; meanwhile, the immobilized enzyme's bonding capacity and
      activity can maintain a relatively high level after surface activation. In
      addition, this material possesses better biocompatibility than chemical
      crosslinked samples. What's more, it can sense the ambient glucose stimulus,
      rapidly and correspondingly adjust its inner pore structure to control the loaded
      metronidazole release, lead to an improved antimicrobial activity against
      Porphyromonas gingivalis under high glucose concentration. This glucose sensitive
      hydrogel film may provide a promising method for diabetic's periodontitis therapy
      in clinic.

PMID- 30287381
TI  - Exopolysaccharides produced by yogurt-texture improving Lactobacillus plantarum
      RS20D and the immunoregulatory activity.
AB  - The strain RS20D capable of significantly improving yogurt texture was isolated
      from traditional fermented vegetable products, and identified as Lactobacillus
      plantarum RS20D. The total exopolysaccharides (EPS) were prepared from
      reconstituted skim milk fermentation by RS20D, and purified through DEAE
      Sepharose CL-6B and Sephadex G-100, and consequently the purified fraction
      designated as RS-r2 was obtained. The further work aimed to elucidate the
      structural features of RS-r2 via FT-IR spectrum, HPSEC and monosaccharide
      composition analysis was carried out. The results showed that RS-r2 was a novel
      acidic heteropolysaccharide mainly consisted of glucose, galactose and
      glucosamine in a molar ratio of 2.0:1.5:1. The molecular weight was estimated to
      be 1.69 * 106 Da. The EPS had a high degradation temperature (250  degrees C),
      suggesting its high thermal stability. SEM and AFM analysis of EPS further
      revealed chain microstructure anchored with many regular spherical shape in
      aqueous solution. In vitro test showed that total EPS secreted by RS20D could
      stimulate macrophage RAW264.7 to release NO significantly and up-regulated the
      gene expression of pro-inflammatory cytokines at the mRNA level. Current study
      suggested that RS20D could be a potential source of immunoregulatory
      polysaccharide and may be applied as a functional starter culture to improve
      yogurt texture in the dairy industry.

PMID- 30287382
TI  - Preparation of high quality starch acetate under grinding and its influence
      mechanism.
AB  - The goal of this study is to reveal mechanism of preparing high quality modified
      starch by advanced equipment in well-known modified starch enterprises. Corn
      starch was used as raw material to prepare starch acetate with low degree of
      substitution under grinding, and the effect of grinding on the quality of starch
      acetate was studied. The effects of grinding on structures and properties of
      native corn starch were investigated. The mechanochemical theory was used to
      analyze the influence mechanism of grinding on quality of starch acetate. The
      results showed that the reaction efficiency (RE) of starch acetate increased from
      70.98% to 85.80% at 4 h of grinding, and other qualities (solubility and swelling
      power) also increased. However, RE and other qualities of starch acetate were
      very different at 12 and 20-60 h of grinding. The changes of structures and
      properties of native starch after grinding showed that grinding has a significant
      mechanochemical effect on corn starch granules. The models of starch molecules
      and granules were made to reveal the "secret" of these advanced equipment in well
      known modified starch enterprises.

PMID- 30287383
TI  - Ultrasensitive immunoassay of glycoprotein 125 (CA 125) in untreated human plasma
      samples using poly (CTAB-chitosan) doped with silver nanoparticles.
AB  - CA 125 is a Mucin glycoprotein and its concentration in human serum correlates
      with a woman's risk of developing ovarian cancer and also indicates response to
      therapy in diagnosed patients. Accurate detection of this large, complex protein
      in patient biofluids is of great clinical relevance. In this work, an innovative
      immunoassay for quantitation of CA 125 based on signal amplification strategy was
      proposed. In this work, Horseradish peroxidase (HRP) labeled CA 125-antibody
      (anti-CA 125) was immobilized onto a green and biocompatible nanocomposite
      containing poly cetyl trimethyl ammonium bromide (P (CTAB) as conductive matrix,
      chitosan (CS) as biocompatible agent and sliver nanoparticles (Ag NPs) as signal
      amplification element. Therefore, a novel nanocomposite film based P (CTAB-CS)
      and Ag NPs was exploited to develop a highly sensitive immunosensor for detection
      of CA 125 protein. Importantly, Ag NPs prepared by electrodeposition method which
      lead to compact morphology. Fully electrochemical methodology was used to prepare
      a new transducer on a glassy carbon surface which provided a high surface area to
      immobilize a high amount of the anti-CA 125. The surface morphology of electrode
      was characterized by high-resolution field emission scanning electron microscope
      (FE-SEM) and energy dispersive spectroscopy (EDS). The immunosensor was employed
      for the detection of CA 125 using cyclic voltammetry (CV) and differential pulse
      voltammetry (DPVs) techniques. Under optimized condition the calibration curve
      for CA 125 concentration by SWV and DPV was linear in 0.01-400 U/mL with lower
      limit of quantification of 0.001 U/mL. The method was successfully applied assay
      of the CA 125 in unprocessed human plasma samples.

PMID- 30287384
TI  - Basolateral amygdala Thy1-expressing neurons facilitate the inhibition of
      contextual fear during consolidation, reconsolidation, and extinction.
AB  - Disrupted fear inhibition is a characteristic of many anxiety disorders.
      Investigations into the neural mechanisms responsible for inhibiting fear will
      improve understanding of the essential circuits involved, and facilitate
      development of treatments that promote their activity. Within the basolateral
      amygdala (BLA), Thy1-expressing neuron activity has been characterized by us and
      others as promoting fear inhibition to discrete fear cues by influencing
      consolidation of cued fear learning or cued fear extinction. Here, we evaluated
      how activating BLA Thy1-expressing neurons using DREADDs affected the
      consolidation, expression, reconsolidation, and extinction of contextual fear.
      Using an inhibitory avoidance paradigm, our present findings indicate a similar
      involvement of BLA Thy1-expressing neuron activity in the consolidation and
      extinction, but not expression, of fear. Importantly, our data also provide the
      first evidence for involvement of these neurons in inhibiting fear
      reconsolidation. Therefore, these data enhance our understanding of the roles
      that Thy1-expressing neurons within the BLA play in inhibiting fear when
      examining avoidance, in addition to the already established role in Pavlovian
      fear paradigms. Future investigations should further explore the circuits
      responsible for these contextual effects modulated by BLA Thy1 neuron activation,
      and could promulgate development of therapies targeting these neurons and their
      downstream effectors.

PMID- 30287385
TI  - Cog4 is required for protrusion and extension of the epithelium in the developing
      semicircular canals.
AB  - The semicircular canals in the inner ear sense angular acceleration. In
      zebrafish, the semicircular canals develop from epithelial projections that grow
      toward each other and fuse to form pillars. The growth of the epithelial
      projections is driven by the production and secretion of extracellular matrix
      components by the epithelium. The conserved oligomeric Golgi 4 protein, Cog4,
      functions in retrograde vesicle transport within the Golgi and mutations can lead
      to sensory neural hearing loss. In zebrafish cog4 mutants, the inner ear is
      smaller and the number of hair cells is reduced. Here, we show that formation of
      the pillars is delayed and that secretion of extracellular matrix components
      (ECM) is impaired in cog4-/- mutants. These results show that Cog4 is required
      for secretion of ECM molecules essential to drive the growth of the epithelial
      projections and thus regulates morphogenesis of the semicircular canals.

PMID- 30287386
TI  - Tailored disorder in calcite organization in tergite cuticle of the supralittoral
      isopod Tylos europaeus Arcangeli, 1938.
AB  - The crustacean cuticle forms skeletal elements consisting of chitin-protein
      fibrils reinforced by amorphous and crystalline calcium carbonate and phosphate
      minerals. The edges of skeletal elements are of particular interest. They are
      subject to repeated strain and stress because they form transitions to the
      arthrodial membranes connecting them. These allow for relative movements of
      skeletal elements. In this study, we investigate structure, chemical composition,
      mineral organization and local mechanical properties of the anterior and
      posterior edges of the tergite cuticle in the conglobating beach isopod Tylos
      europaeus and compare these with the protective dorsal region of the tergites.
      The distribution of mineral phases at the edges resembles that of dorsal regions
      of the tergites. At the transition with the unmineralized arthrodial membrane the
      calcite containing distal exocuticle is replaced by epicuticular material and the
      subjacent cuticular layers containing amorphous calcium carbonate become enriched
      with amorphous calcium phosphate. At the edges, the local elastic modulus and
      hardness values are significantly lower compared to dorsal regions of the tergite
      cuticle, for both, the calcite and the amorphous mineral containing layers. The
      calcite within the tergite cuticle is assembled in different texture patterns:
      (i) almost random co-orientation, (ii) almost single crystalline calcite, and
      (iii) a graded organization. Calcite organization and co-orientation strength is
      highly variable, not only on very few tens of micrometres, but also between
      regions with different skeletal functionality. Our results show that besides
      structure and composition, patterns of calcite organization contribute to the
      hierarchical architecture and functionality of biological composites.

PMID- 30287387
TI  - Crystal structure of a biliverdin-bound phycobiliprotein: Interdependence of
      oligomerization and chromophorylation.
AB  - Small, ultra-red fluorescence protein (smURFP) introduces the non-native
      biliverdin (BV) chromophore to phycobiliproteins (PBPs), allowing them to be used
      as transgenic labels for in vivo mammalian imaging. Presently, no structural
      information exists for PBPs bound to the non-native BV chromophore, which limits
      the further development of smURFP and related proteins as imaging labels or
      indicators. Here we describe the first crystal structure of a PBP bound to BV.
      The structures of smURFP-Y56R with BV and smURFP-Y56F without BV reveal unique
      oligomerization interfaces different from those in wild-type PBPs bound to native
      chromophores. Our structures suggest that the oligomerization interface affects
      the BV binding site, creating a link between oligomerization and
      chromophorylation that we confirmed through site-directed mutagenesis and that
      may help guide efforts to improve the notorious chromophorylation of smURFP and
      other PBPs engineered to bind BV.

PMID- 30287388
TI  - Tenascins in CNS lesions.
AB  - The tenascin family of glycoproteins comprises four members in vertebrates, of
      which tenascin-C (Tnc) and tenascin-R (Tnr) are particularly important in the
      context of lesions in the central nervous system (CNS). Tnc is expressed in the
      developing CNS, before it is down-regulated and mainly restricted to the adult
      neural stem cell niches. It regulates numerous processes including
      differentiation, adhesion, migration and neurite outgrowth. These aspects are
      critical in the developing organism, but also after damage. Interestingly, Tnc is
      indeed re-expressed in the injured CNS. Additionally, Tnc is an activator of the
      immune response, another important aspect after lesion. Tnr is part of
      perineuronal nets, a specialized form of extracellular matrix that enwraps
      subtypes of neurons and limits synaptic plasticity. We summarize the role of
      tenascins in the context of stem cell niches, barrier formation, synaptic
      plasticity and immune response in the damaged mammalian CNS.

PMID- 30287389
TI  - Enriched environment regulates thymocyte development and alleviates experimental
      autoimmune encephalomyelitis in mice.
AB  - Environmental and social factors have profound impacts on immune homeostasis. Our
      work on environmental enrichment (EE) has revealed a novel anti-obesity and
      anticancer phenotype associated with enhanced activity of CD8+ cytotoxic T
      lymphocytes in secondary lymphoid tissues. Here we investigated how an EE
      modulated thymus and thymocyte development. EE decreased thymus mass and
      cellularity, decreased the double positive thymocyte population, increased the
      proportion of CD8+ T cells, reduced the CD4:CD8 ratio, and downregulated CD69
      expression in T cells. In a model of multiple sclerosis: experimental autoimmune
      encephalomyelitis (EAE), EE alleviated symptoms, inhibited spinal cord
      inflammation through regulation of type 1 T-helper cells mediated by
      glucocorticoid receptor signaling, and prevented EAE-induced thymic disturbance.
      Our mechanistic studies demonstrated that hypothalamic BDNF activated a
      hypothalamic-pituitary-adrenal axis mediating the EE's thymic effects. Our
      results indicate that a lifestyle intervention links the nervous, endocrine, and
      adaptive immune system, allowing the body to adapt to internal and external
      environments.

PMID- 30287391
TI  - Effect of dose and exposure protocol on the toxicokinetics and first-pass
      elimination of trichloroethylene and 1,1,1-trichloroethane.
AB  - Trichloroethylene (TCE) and 1,1,1-trichloroethane (TRI) are frequent contaminants
      of drinking water and of groundwater at hazardous waste sites. There is
      relatively little information on the target organ deposition of TRI, despite its
      ingestion and common occurrence in humans. An important aim of the study was to
      delineate and contrast the toxicokinetics (TK) and bioavailability (F) of TRI and
      its well metabolized congener, TCE. Blood profiles were obtained from male
      Sprague-Dawley rats given aqueous emulsions of 6 or 48 mg TRI/kg and 10 or 50 mg
      TCE/kg as an oral bolus (po) or by gastric infusion (gi) over 2 h. TCE exhibited
      nonlinear TK, with a disproportionate increase in AUC and decrease in clearance
      and F with increase in dose. TRI exhibited linear TK. F did not vary
      significantly with TRI dose or dosage regimen. F values were substantially higher
      for TRI than for the respective TCE groups. TRI was distributed widely to tissues
      of rats gavaged with 6 mg TRI/kg, with accumulation in fat. This experiment
      yielded tissue uptake and elimination profiles and in vivo tissue:blood partition
      coefficients (PCs). Finally, additional rats were given 10 mg/kg of TCE and TRI
      po, ia and iv, so that first-pass hepatic (FPh) and pulmonary (FPp) elimination
      could be measured directly. Total and FPh elimination of TCE exceeded that of
      TRI. TRI, with its higher air:blood PC, exhibited the higher FPp. TCE and TRI,
      despite several common physical and chemical properties resulting in similar
      absorption and systemic distribution, displayed dissimilar dosage and dose rate
      effects on their TK.

PMID- 30287390
TI  - Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell
      Transplantation.
AB  - We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation
      (HCT) recipients reported to the Center for International Blood and Marrow
      Transplant Research. We analyzed the incidence, infection types, and risk factors
      contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for >=2
      years after first HCT without relapse. Among 2245 adult and 377 pediatric
      patients who died, infections were a primary or contributory cause of death in
      687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative
      incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in
      adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P <
      .001). In adults, the 2 most significant risks for developing LFI were increasing
      age (20 to 39, 40 to 54, and >=55 years versus 18 to 19 years) with hazard ratios
      (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95%
      CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD
      (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no
      history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the
      3 most significant risks for developing LFI were a history of cGVHD with ongoing
      immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing
      immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-HCT compared
      with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte
      function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI,
      1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study
      emphasizes the importance of continued vigilance for late infections after HCT
      and institution of support strategies aimed at decreasing the risk of cGVHD.

PMID- 30287392
TI  - Mechanisms controlling the multistage post-translational processing of endogenous
      Nrf1alpha/TCF11 proteins to yield distinct isoforms within the coupled positive
      and negative feedback circuits.
AB  - To gain a better understanding of the multistep processing of Nrf1 to yield
      various isoforms with confused molecular masses, we herein establish a generally
      acceptable criterion required for identification of its endogenous full-length
      proteins and derivative isoforms expressed differentially in distinct
      experimental cell lines. Further work has been focused on the molecular
      mechanisms that dictate the successive post-translational modifications (i.e.
      glycosylation by OST, deglycosylation by NGLY, and ubiquitination by Hrd1) of
      this CNC-bZIP protein and its proteolytic processing to give rise to multiple
      proteoforms. Several lines of experimental evidence have demonstrated that the
      nascent Nrf1alpha/TCF11 polypeptide (non-glycosylated) is transiently
      translocated into the endoplasmic reticulum (ER), in which it becomes an inactive
      glycoprotein-A, and is folded in a proper topology within and around membranes.
      Thereafter, dynamic repositioning of the ER-resident domains in Nrf1 glycoprotein
      is driven by p97-fueled retrotranslocation into extra-ER compartments. Therein,
      Nrf1 glycoprotein is allowed for deglycosylation digestion by glycosidases into a
      deglycoprotein-B and its progressive proteolytic processing by cytosolic DDI-1/2
      and proteasomes so as to generate N-terminally-truncated protein-C/D. This
      processing is accompanied by removal of a major N-terminal ~12.5-kDa polypeptide
      from Nrf1alpha. Interestingly, our present study has further unraveled that there
      exist coupled positive and negative feedback circuits between Nrf1 and cognate
      target genes, including those encoding its regulators p97, Hrd1, DDI-1 and
      proteasomes. These key players are differentially or even oppositely involved in
      diverse cellular signaling responses to distinct extents of ER-derived
      proteotoxic and oxidative stresses induced by different concentrations of
      proteasomal inhibitors.

PMID- 30287394
TI  - Update on How School Environments, Social Networks, and Self-Concept Impact Risky
      Health Behaviors.

PMID- 30287393
TI  - Satisfaction, Salaries and Sustainability: Results of a National Survey of
      Pediatric Program Directors.
AB  - OBJECTIVES: Describe the career and work environment of pediatric program
      directors (PDs) and associated factors, including salary disparities and long
      term career plans. METHODS: A national, anonymous, electronic survey was sent to
      all categorical residency PD members of the Association of Pediatric Program
      Directors (APPD). Surveys assessed PD demographics, characteristics of the
      residency program and the PDs' positions (including salary), and measures of
      satisfaction. Chi-square and Fisher's exact test were used to analyze results.
      RESULTS: 149 PDs (74%) responded. Significantly more men earned $250,000 or more
      annually (26.9% versus 6.1% of women), and gender remained a significant
      independent predictor of salary after controlling for age, academic rank and
      subspecialty. Satisfaction was high for most measures, although 20% or more
      reported low satisfaction with pay (38.9%), administrative workload (32.1%),
      managing accreditation and ACGME expectations (31.9%), resources (27.9%),
      work/life balance (24.1%), and being valued by administration (20.0%). Only 34.3%
      saw the PD position as an end goal, and 29.5% stated they would be in their
      current position in 5 years. Satisfaction with the PD career, with faculty
      relationships, with resident performance, and with administrative workload were
      associated with plans to remain. CONCLUSIONS: Most Pediatric Program Directors
      did not view the position of PD as their long-term career goal, and many
      identified administrative duties and work/life balance contributing to
      significant dissatisfaction. Without changes to address these issues, PD turnover
      may be high, with potential negative implications for the success of training
      programs.

PMID- 30287395
TI  - 3D morphometric analysis of calcified cartilage properties using micro-computed
      tomography.
AB  - OBJECTIVE: Our aim is to establish methods for quantifying morphometric
      properties of calcified cartilage (CC) from micro-computed tomography (MUCT).
      Furthermore, we evaluated the feasibility of these methods in investigating
      relationships between osteoarthritis (OA), tidemark surface morphology and open
      subchondral channels (OSCCs). METHOD: Samples (n = 15) used in this study were
      harvested from human lateral tibial plateau (n = 8). Conventional roughness and
      parameters assessing local 3-dimensional (3D) surface variations were used to
      quantify the surface morphology of the CC. Subchondral channel properties
      (percentage, density, size) were also calculated. As a reference, histological
      sections were evaluated using Histopathological osteoarthritis grading (OARSI)
      and thickness of CC and subchondral bone (SCB) was quantified. RESULTS: OARSI
      grade correlated with a decrease in local 3D variations of the tidemark surface
      (amount of different surface patterns (rs = -0.600, P = 0.018), entropy of
      patterns (EP) (rs = -0.648, P = 0.018), homogeneity index (HI) (rs = 0.555, P =
      0.032)) and tidemark roughness (TMR) (rs = -0.579, P = 0.024). Amount of
      different patterns (ADP) and EP associated with channel area fraction (CAF) (rp =
      0.876, P < 0.0001; rp = 0.665, P = 0.007, respectively) and channel density (CD)
      (rp = 0.680, P = 0.011; rp = 0.582, P = 0.023, respectively). TMR was associated
      with CAF (rp = 0.926, P < 0.0001) and average channel size (rp = 0.574, P =
      0.025). CC topography differed statistically significantly in early OA vs healthy
      samples. CONCLUSION: We introduced a MU-CT image method to quantify 3D CC
      topography and perforations through CC. CC topography was associated with OARSI
      grade and OSCC properties; this suggests that the established methods can detect
      topographical changes in tidemark and CC perforations associated with OA.

PMID- 30287396
TI  - A graphic user interface for the evaluation of knee osteoarthritis (GEKO): an
      open-source tool for histological grading.
AB  - OBJECTIVE: In osteoarthritis (OA) models, histology is commonly used to evaluate
      the severity of joint damage. Unfortunately, semi-quantitative histological
      grading systems include some level of subjectivity, and quantitative grading
      systems can be tedious to implement. The objective of this work is to introduce
      an open source, graphic user interface (GUI) for quantitative grading of knee OA.
      METHODS: Inspired by the 2010 OARSI histopathology recommendations for the rat,
      our laboratory has developed a GUI for the evaluation of knee OA, nicknamed GEKO.
      In this work, descriptions of the quantitative measures acquired by GEKO are
      presented and measured in 42 histological images from a rat knee OA model. Using
      these images, across-session and within-session reproducibility for individual
      graders is evaluated, and inter-grader reliability across different levels of OA
      severity is also assessed. RESULTS: GEKO allowed histological images to be
      quantitatively scored in less than 1 min per image. In addition, intra-class
      coefficients (ICCs) were largely above 0.8 for across-session reproducibility,
      within-session reproducibility, and inter-grader reliability. These data indicate
      GEKO aided in the reproducibility and repeatability of quantitative OA grading
      across graders and grading sessions. CONCLUSIONS: Our data demonstrate GEKO is a
      reliable and efficient method to calculate quantitative histological measures of
      knee OA in a rat model. GEKO reduced quantitative grading times relative to
      manual grading systems and allowed grader reproducibility and repeatability to be
      easily assessed within a grading session and across time. Moreover, GEKO is being
      provided as a free, open-source tool for the OA research community.

PMID- 30287397
TI  - A systematic review of the small molecule studies of osteoarthritis using nuclear
      magnetic resonance and mass spectroscopy.
AB  - OBJECTIVE: To perform a systematic review of the small molecule metabolism
      studies of osteoarthritis utilising nuclear magnetic resonance (NMR) or mass
      spectroscopy (MS) analysis (viz., metabolomics or metabonomics), thereby
      providing coherent conclusions and reference material for future study. METHOD:
      We applied PRISMA guidelines (PROSPERO 95068) with the following MESH terms: 1.
      "osteoarthritis" AND ("metabolic" OR "metabonomic" OR "metabolomic" OR
      "metabolism") 2. ("synovial fluid" OR "cartilage" OR "synovium" OR "serum" OR
      "plasma" OR "urine") AND ("NMR" or "Mass Spectroscopy"). Databases searched were
      "Medline" and "Embase". Studies were searched in English and excluded review
      articles not containing original research. Study outcomes were significant or
      notable metabolites, species (human or animal) and the Newcastle-Ottawa Score.
      RESULTS: In the 27 studies meeting the inclusion criteria, there was a shift
      towards anaerobic and fatty acid metabolism in OA disease, although whether this
      represents the inflammatory state remains unclear. Lipid structure and
      composition was altered within disease subclasses including phosphatidyl choline
      (PC) and the sphingomyelins. Macromolecular proteoglycan destruction was
      described, but the correlation to disease factors was not demonstrated. Collated
      results suggested arachidonate signalling pathways and androgen sex hormones as
      future metabolic pathways for investigation. CONCLUSION: Our meta-analysis
      demonstrates significant small molecule differences between sample types, between
      species (such as human and bovine), with potential OA biomarkers and targets for
      local or systemic therapies. Studies were limited by numbers and a lack of
      disease correlation. Future studies should use NMR and MS analysis to further
      investigate large population subgroups including inflammatory arthropathy, OA
      subclasses, age and joint differences.

PMID- 30287399
TI  - Hyperglycosylated hCG activates LH/hCG-receptor with lower activity than hCG.
AB  - While human chorionic gonadotropin (hCG) appears to have an essential role in
      early pregnancy, it is controversial whether the hyperglycosylated form of hCG
      (hCG-h), which is the major hCG isoform during the first 4-5 weeks of pregnancy,
      is able to activate LH/hCG receptor (LHCGR). To address this, we utilized
      different extensively characterized hCG and hCGbeta reference reagents, cell
      culture- and urine-derived hCG-h preparations, and an in vitro reporter system
      for LHCGR activation. The WHO hCG reference reagent (99/688) was found to
      activate LHCGR with an EC50-value of 3.3 +/- 0.6 pmol/L (n = 9). All three
      studied hCG-h preparations were also able to activate LHCGR, but with a lower
      potency (EC50-values between 7.1 +/- 0.5 and 14 +/- 3 pmol/L, n = 5-11, for all P
      < 0.05 as compared to the hCG reference). The activities of commercial urinary
      hCG (Pregnyl) and recombinant hCG (Ovitrelle) preparations were intermediate
      between those of the hCG reference and the hCG-h. These results strongly suggest
      that the hCG-h is functionally similar to hCG, although it has lower potency for
      LHCGR activation. Whether this explains the reduced proportion of hCG-h to hCG
      reported in patients developing early onset pre-eclampsia or those having early
      pregnancy loss remains to be determined.

PMID- 30287398
TI  - Social and neuromolecular phenotypes are programmed by prenatal exposures to
      endocrine-disrupting chemicals.
AB  - Exposures to endocrine-disrupting chemicals (EDCs) affect the development of
      hormone-sensitive neural circuits, the proper organization of which are necessary
      for the manifestation of appropriate adult social and sexual behaviors. We
      examined whether prenatal exposure to polychlorinated biphenyls (PCBs), a family
      of ubiquitous industrial contaminants detectable in virtually all humans and
      wildlife, caused changes in sexually-dimorphic social interactions and
      communications, and profiled the underlying neuromolecular phenotype. Rats were
      treated with a PCB commercial mixture, Aroclor 1221 (A1221), estradiol benzoate
      (EB) as a positive control for estrogenic effects of A1221, or the vehicle (4%
      DMSO), on embryonic day (E) 16 and 18. In adult F1 offspring, we first conducted
      tests of ultrasonic vocalization (USV) calls in a sociosexual context as a
      measure of motivated communications. Numbers of certain USV call types were
      significantly increased by prenatal treatment with A1221 in males, and decreased
      by EB in females. In a test of sociosexual preference for a hormone-vs. a non
      hormone-primed opposite sex conspecific, male (but not female) nose-touching with
      opposite-sex rats was significantly diminished by EDCs. Gene expression profiling
      was conducted in two brain regions that are part of the social decision-making
      network in the brain: the medial preoptic nucleus (MPN) and the ventromedial
      nucleus (VMN). In both regions, many more genes were affected by A1221 or EB in
      females than males. In female MPN, A1221 changed expression of steroid hormone
      receptor and neuropeptide genes (e.g., Ar, Esr1, Esr2, and Kiss1). In male MPN,
      only Per2 was affected by A1221. The VMN had a number of genes affected by EB
      compared to vehicle (females: Kiss1, Kiss1r, Pgr; males: Crh) but not A1221.
      These differences between EB and A1221 indicate that the mechanism of action of
      A1221 goes beyond estrogenic pathways. These data show sex-specific effects of
      prenatal PCBs on adult behaviors and the neuromolecular phenotype.

PMID- 30287400
TI  - A review on the mechanism of iodide metabolic dysfunction in differentiated
      thyroid cancer.
AB  - The incidence of differentiated thyroid cancer (DTC) has been increasing rapidly
      worldwide, and the risk factors remain unclear. With the growing number of
      patients with DTC, the related issues have been gradually highlighted. 131Iodide
      (131I) is an important treatment for DTC and has the potential to reduce the risk
      of recurrence. 131I is also an effective treatment for distant metastases of
      thyroid carcinoma. However, iodide metabolism dysfunction in metastatic foci
      causes patients to lose the opportunity of 131I treatment. This article reviews
      the related mechanisms of iodide metabolism dysfunction in DTC cells and
      summarizes the clinical transformation progression.

PMID- 30287401
TI  - Identification and comparative analysis of the miRNA expression profiles from
      four tissues of Micropterus salmoides using deep sequencing.
AB  - In the present study, four small RNA libraries were constructed from an M.
      salmoides population and sequenced using deep sequencing technology. A total of
      9,888,822; 8,519,365; 20,566,198; and 15,762,254 raw reads representing 666,097;
      755,711; 978,923; and 840,175 unique sequences were obtained from the spleen,
      liver, kidney, and muscle libraries, respectively. As a result, 509 known miRNAs
      belonging to 143 families and 1157 novel miRNAs were identified. The miRNAs
      displayed diverse expression levels among the four libraries, among which most of
      the known miRNAs were expressed at higher levels than the novel miRNAs.
      Furthermore, stem-loop qRT-PCR was applied to validate and profile the expression
      of the differentially expressed miRNAs in the four different tissues, which
      revealed that some miRNAs showed tissue specific expression. The identification
      of miRNAs in M. salmoides will provide new information and enhance our
      understanding of the functions of miRNAs in regulating biological processes.

PMID- 30287402
TI  - Pathogenicity, Phylogenetic relationship and NGS based identification and
      assembly of tumorigenic Agrobacterium radiabacter plasmidic and chromosomic reads
      isolated from Prunus duclcis.
AB  - Although many Agrobacterium radiobacter strains have already been identified,
      only a few genomes of strains belonging to genomovar G4 have been sequenced so
      far. In this study, we report the first virulent genome sequence of Agrobacterium
      radiobacter strain tun 183, which is highly virulent to almond specie. The genome
      size was estimated to be 5.53 Mb, with 57.9%GC content. In total, 6486 genes
      encoding proteins and 61 genes encoding RNAs were identified in this genome.
      Comparisons with the available sequenced genomes of genomovar G4 as well as with
      other A. sp. were conducted, revealing a hexapartite genome containing circular
      and linear chromosomes in addition to two accessory plasmids and a tumor inducing
      plasmid (pTi) in strain tun 183. The phylogenetic analysis of recA gene clearly
      showed the clustering of tun 183 strain within genomovar G4, supporting the
      monophyly within this genomovar.

PMID- 30287403
TI  - A powerful method to integrate genotype and gene expression data for dissecting
      the genetic architecture of a disease.
AB  - To decipher the genetic architecture of human disease, various types of omics
      data are generated. Two common omics data are genotypes and gene expression.
      Often genotype data for a large number of individuals and gene expression data
      for a few individuals are generated due to biological and technical reasons,
      leading to unequal sample sizes for different omics data. Unavailability of
      standard statistical procedure for integrating such datasets motivates us to
      propose a two-step multi-locus association method using latent variables. Our
      method is powerful than single/separate omics data analysis and it unravels
      comprehensively deep-seated signals through a single statistical model. Extensive
      simulation confirms that it is robust to various genetic models as its power
      increases with sample size and number of associated loci. It provides p-values
      very fast. Application to real dataset on psoriasis identifies 17 novel SNPs,
      functionally related to psoriasis-associated genes, at much smaller sample size
      than standard GWAS.

PMID- 30287404
TI  - Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence
      condition that fosters progression of retinopathy and nephropathy.
AB  - The increased prevalence of type 2 diabetes mellitus (T2DM) and life expectancy
      of diabetic patients fosters the worldwide prevalence of retinopathy and
      nephropathy, two major microvascular complications that have been difficult to
      treat with contemporary glucose-lowering medications. The gut microbiota (GM) has
      become a lively field research in the last years; there is a growing recognition
      that altered intestinal microbiota composition and function can directly impact
      the phenomenon of ageing and age-related disorders. In fact, human GM, envisaged
      as a potential source of novel therapeutics, strongly modulates host immunity and
      metabolism. It is now clear that gut dysbiosis and their products (e.g. p-cresyl
      sulfate, trimethylamine-N-oxide) dictate a secretory associated senescence
      phenotype and chronic low-grade inflammation, features shared in the
      physiological process of ageing ("inflammaging") as well as in T2DM
      ("metaflammation") and in its microvascular complications. This review provides
      an in-depth look on the crosstalk between GM, host immunity and metabolism.
      Further, it characterizes human GM signatures of elderly and T2DM patients.
      Finally, a comprehensive scrutiny of recent molecular findings (e.g. epigenetic
      changes) underlying causal relationships between GM dysbiosis and diabetic
      retinopathy/nephropathy complications is pinpointed, with the ultimate goal to
      unravel potential pathophysiological mechanisms that may be explored, in a near
      future, as personalized disease-modifying therapeutic approaches.

PMID- 30287405
TI  - TLR4 triggered complex inflammation in human pancreatic islets.
AB  - Type 2 Diabetes (T2D) is strongly associated with obesity and inflammation. Toll
      like receptor-4 (TLR-4) is the major pro-inflammatory pathway with its ligands
      and downstream products increased systemically in T2D and in at-risk individuals.
      Detailed mechanisms of the complex proinflammatory response in pancreatic islets
      remain unknown. In isolated human islets LPS induced IL-1beta, IL-6, IL-8 and TNF
      production in a TLR4-dependent manner and severely impaired beta-cell survival
      and function. IL-6 antagonism improved beta-cell function. IL-8, which was
      identified specifically in alpha-cells, initiated monocyte migration, a process
      fully blocked by IL-8 neutralization. The TLR4 response was potentiated in obese
      donors; with higher IL-1beta, IL-6 and IL-8 expression than in non-obese donors.
      TLR4 activation leads to a complex multi-cellular inflammatory response in human
      islets, which involves beta-cell failure, cytokine production and macrophage
      recruitment to islets. In obesity, the amplified TLR4 response may potentiate
      beta-cell damage and accelerate diabetes progression.

PMID- 30287407
TI  - Development and validation of an optimized finite element model of the human
      orbit.
AB  - INTRODUCTION: The authors' main purpose was to develop a detailed finite element
      model (FEM) of the human orbit and to validate it by analyzing its behavior under
      the stress of blunt traumas. MATERIALS AND METHODS: A pre-existing 3D FEM of a
      human head was modified and used in this study. Modifications took into account
      preliminary research carried out on PubMed database. Data from a CT scan of the
      head were computed with Mimics(r) software to re-create the skull geometry. The
      mesh production, the model's properties and the simulations of blunt orbital
      traumas were conducted on Hyperworks(r) software. RESULTS: The resulting 3D FEM
      was composed of 640 000 elements and was used to perform blunt trauma simulations
      on an intact orbit. A total of 27 tests were simulated. 15 tests were realized
      with a metallic cylinder impactor; 12 tests simulated a hit by a closed fist. In
      all the tests conducted (27/27), the orbital floor was fractured. Fracture
      patterns were similar to those found in real clinical situations according to the
      buckling and hydraulic theories of orbital floor fractures. DISCUSSION: The
      similitude between the fracture patterns produced on the model and those observed
      in vivo allows for a validation of the model. This model constitutes, at the
      authors knowledge, the most sophisticated one ever developed.

PMID- 30287406
TI  - Comparative analysis of iTRAQ-based proteomes for cocoons between the domestic
      silkworm (Bombyx mori) and wild silkworm (Bombyx mandarina).
AB  - : The domestic silkworm Bombyx mori was domesticated from wild silkworm B.
      mandarina about 5000 years ago. Long-term domestication and breeding selection
      have led to the weight of domestic silkworm cocoon being ten times greater than
      that of wild silkworm cocoon. However, we found that wild silkworm cocoon has
      significantly much more abundance of sericin proteins than domestic silkworm
      cocoon. Strikingly, we found that many protease inhibitors have been
      significantly down-regulated in domestic silkworm cocoon compared with its wild
      progenitor by using isobaric tag for relative and absolute quantitation (iTraq)
      approach. Both real-time qPCR experiment and transcriptome data in silk gland
      also verified these results. In addition, our data indicated that protease
      inhibitor activity of wild silkworm cocoon was stronger than that of domestic
      silkworm cocoon, implying that relatively up-regulated protease inhibitors in
      wild silkworm cocoon may play protection roles against microorganisms. Thus,
      these protease inhibitors up-regulated in wild silkworm cocoon may have potential
      values in sericulture and medical practice. SIGNIFICANCE: This study revealed
      that there is a big difference in abundance of sericin proteins in cocoon between
      domestic and wild silkworms. Strikingly, many protease inhibitors have been
      significantly down-regulated in domestic silkworm cocoon compared with its wild
      progenitor. This may be due to different environments where the two silkworms
      live. In addition, the results also implied that relatively up-regulated protease
      inhibitors in wild silkworm cocoon may play protection roles against
      microorganisms. Thus, these protease inhibitors may have potential values in
      sericulture and medical practice.

PMID- 30287408
TI  - Combined use of biocompatible nanoemulsions and solid microneedles to improve
      transport of a model NSAID across the skin: In vitro and in vivo studies.
AB  - This study aimed to investigate the potential of lecithin-based nanoemulsions
      costabilized by sucrose esters, with and without skin pretreatment with stainless
      steel microneedles, to improve delivery of aceclofenac, as a model drug,
      into/across the skin. The characterization revealed favorable droplet size (about
      180 nm), narrow size distribution (<0.15), high surface charge (about -40 mV) and
      satisfying long-term stability (one year at 4 +/- 1  degrees C) of the
      formulation costabilized by sucrose palmitate, demonstrating a similar trend
      observed for the reference stabilized by widely used lecithin/polysorbate 80
      combination. In vitro release/permeation testing and differential stripping on
      the porcine ear proved the superiority of the sucrose ester- over polysorbate
      based nanoemulsion. However, in vitro findings were not fully indicative of the
      in vivo performances - no significant differences were observed between
      investigated formulations in pharmacokinetic profile and total amount of
      aceclofenac deposited in the rat skin 24 h after dosing, simultaneously pointing
      to delayed aceclofenac delivery into the systemic circulation. In addition, the
      ratio of plasma concentrations of aceclofenac and its major metabolite in rats,
      diclofenac, was remarkably changed after topical application of tested
      nanoemulsions compared to intravenous administration of aceclofenac solution.
      Finally, skin pretreatment with microneedles improved aceclofenac delivery
      into/across the rat skin from tested formulations, resulting in 1.4-2.1-fold
      increased bioavailability and 1.2-1.7-fold enhanced level of aceclofenac retained
      in the skin, as measured 24 h after administration. Moreover, the plasma
      concentrations of aceclofenac 24 h after application of tested formulations
      (lecithin/sucrose palmitate vs. lecithin/polysorbate 80) combined with
      microneedles (173.37 +/- 40.50 ng/ml vs. 259.23 +/- 73.18 ng/ml) were
      significantly higher than those obtained through intact skin (105.69 +/- 19.53
      ng/ml vs. 88.38 +/- 14.46 ng/ml). However, obtained results suggest that
      combination of microneedles and sucrose palmitate-costabilized nanoemulsion could
      be useful to attain higher skin concentration, while combination of microneedles
      with polysorbate 80-costabilized nanoemulsion could be a preferable option for
      enhancing drug delivery into the bloodstream.

PMID- 30287409
TI  - The effect of amorphous and crystal sodium warfarin and its content uniformity on
      bioequivalence of tablets.
AB  - Warfarin is intensively discussed in terms of generic substitution due to
      particular cases of bleeding, which are attributable to fluctuations in API
      content or the substitution of crystalline (WSC) for amorphous (WSA) warfarin.
      The aim of this study was to assess to what extent the in vitro release was
      affected by the form of API depending on the composition and technology.
      Bioequivalent tablets containing 5 mg of WSA or WSC prepared by wet granulation
      or direct compression were used. Furthermore, tablets of the same composition
      with WSC or WSA prepared by direct compression were evaluated. Raman spectroscopy
      was used to confirm the presence of WSA or WSC. The dissolution was more
      influenced by the technology than by the form of API but even tablets with
      dissimilar profiles were bioequivalent. This is probably due to the precipitation
      of WSA and WSC in the stomach on a poorly soluble acidic form, which subsequently
      dissolves in the neutral environment of the small intestine. Recrystallization
      was demonstrated in the in vitro assay at a pH of 1.2 and 4.5 using Raman
      spectroscopy and X-ray diffraction. In summary, the content uniformity appears to
      be the main factor affecting the safety of the treatment.

PMID- 30287410
TI  - Strategies to improve the prediction accuracy of hepatic intrinsic clearance of
      three antidiabetic drugs: Application of the extended clearance concept and
      consideration of the effect of albumin on CYP2C metabolism and OATP1B-mediated
      hepatic uptake.
AB  - The antidiabetic drugs glibenclamide, repaglinide, and nateglinide are well-known
      substrates for hepatic uptake transporters of the organic anion transporting
      polypeptide (OATP) family and metabolizing enzymes of the cytochrome P450 (CYP)
      2C subfamily. The systemic exposure of these drugs varies substantially among
      individuals, impacted by genetic polymorphisms of transporters and metabolizing
      enzymes as well as drug-drug interactions. The use of the conventional in vitro
      in vivo extrapolation (IVIVE) method was found to underestimate their hepatic
      intrinsic clearance (CLint,all); the clinically observed CLint,all values were
      >=10-fold higher than the predicted values from in vitro data. In order to
      improve the accuracy in predicting CLint,all of these drugs, the following
      modifications were implemented; i) the extended clearance concept was applied
      during IVIVE processes, ii) albumin was added to metabolic assays using human
      liver microsomes (to minimize the impact of intrinsic inhibitors on kinetic
      parameters for CYP2C-mediated metabolism) and to hepatic uptake assays (to
      accommodate the enhanced hepatic uptake observed with albumin-bound drugs), and
      iii) differing rates of efflux and influx via diffusion were used. The IVIVE
      method with these modifications yielded the predicted CLint,all values from in
      vitro data in closer agreement with the CLint,all values observed in vivo; the
      fold differences between the predicted and observed CLint,all values reduced from
      13-15 to 5.9-6.7. Our current approach offers an improvement in the prediction of
      CLint,all and further investigations are warranted to enhance the prediction
      accuracy of IVIVE.

PMID- 30287411
TI  - Non-specific symptoms in adult patients referred to a Lyme centre.
AB  - OBJECTIVES: There is controversy whether non-specific symptoms can be related to
      previous Lyme borreliosis (LB). Positive serology can be considered a proxy for
      previous or persistent LB. We assessed non-specific symptoms and serology in
      patients suspected of LB referred to a Lyme centre. METHODS: Included were adult
      patients who visited a Lyme centre between 2008 and 2014. Before medical
      consultation, serum samples were taken and questionnaires on non-specific
      symptoms completed. The prevalence of non-specific symptoms was calculated for
      patients with positive and negative IgG serology. Logistic regression was used to
      obtain odds ratios (ORs) with 95% confidence interval (CI) for an association
      between positive serology and non-specific symptoms. RESULTS: Of 1439 included
      patients, 31.6% (455/1439) had positive serology. The most common non-specific
      symptoms were severe fatigue (61.4%, 883/1439), sleep disturbances (54.8%,
      789/1439) and stiffness of neck/back (52.6%, 757/1439). The prevalence of severe
      fatigue was 53.0% (241/455) in patients with positive serology vs. 65.2%
      (642/984) in patients with negative serology (OR = 0.74; 95% CI, 0.58-0.94). The
      prevalence of sleep disturbances was respectively 46.2% (210/455) vs. 58.8%
      (579/984) (OR = 0.73; 95% CI, 0.58-0.93). The prevalence of stiffness of
      neck/back was respectively 47.7% (217/455) vs. 54.9% (540/984) (OR = 0.85; 95%
      CI, 0.67-1.06). CONCLUSIONS: In patients referred to a Lyme centre, non-specific
      symptoms did not occur more frequently in patients with positive serology
      compared to patients with negative serology. Hence, a questionnaire on non
      specific symptoms cannot be used for identifying patients with possible post-LB
      symptoms in clinical practice.

PMID- 30287412
TI  - Impact of Antimicrobial Treatment Duration on Outcome of Staphylococcus aureus
      Bacteremia: A Cohort Study.
AB  - OBJECTIVES: We aimed to assess the outcome of Staphylococcus aureus bacteremia
      (SAB) according to factors associated with necessity for longer treatment in
      conjunction with the duration of treatment. METHODS: We prospectively collected
      the data of patients with SAB consecutively during 12-39 months from 11
      hospitals. If multiple episodes of SAB occurred in one patient, only the first
      episode was enrolled. Factors associated with necessity for longer treatment were
      defined as follows: persistent bacteremia, metastatic infection, prosthesis, and
      endocarditis. If any of the factors were present, the case was defined as longer
      antibiotic treatment warranted (LW) group, those without any factors were defined
      as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined
      as composite of 90-day mortality or 30-day recurrence. Duration of antibiotic
      administration was classified as <14 or >=14 days in SS-group, and <28 or >=28
      days in LW-group. RESULTS: Among 2098 cases, the outcome was analyzed in 1866
      cases, of which 591 showed poor outcome. SS-group accounted for 964 cases and LW
      group for 852 cases. On multivariate analysis, age over 65 years, pneumonia,
      higher SOFA score, chronic liver diseases were risk factors for poor outcome.
      Administration of antibiotics less than the recommendation was associated with
      poor outcome, but this significance was observed only in the LW-group (adjusted
      odds ratio 1.68, 95% confidence interval 1.00-2.83, p=0.05). CONCLUSIONS:
      Inappropriately short antibiotic treatment was associated with poor outcome in
      the LW-group. Vigilant evaluation for risk factors to determine the duration of
      treatment may improve the outcome among patients with SAB.

PMID- 30287413
TI  - 'How to do it'-molecular investigation of a hospital outbreak.
AB  - BACKGROUND: Studying hospital outbreaks by using molecular tools, i.e.
      synthesizing the molecular epidemiology data to its appropriate clinical
      epidemiologic context, is crucial in order to identify infection source, infer
      transmission dynamics, appropriately allocate prevention resources and implement
      control measures. Whole-genome sequencing (WGS) of pathogens has become the
      reference standard, as it is becoming more accessible and affordable.
      Consequently, sequencing of the full pathogen genome via WGS and major progress
      in fit-for-purpose genomic data analysis tools and interpretation is
      revolutionizing the field of outbreak investigations in hospitals. Metagenomics
      is an additional evolving field that might become commonly used in the future for
      outbreak investigations. Nevertheless, practitioners are frequently limited in
      terms of WGS or metagenomics, especially for local outbreak analyses, as a result
      of costs or logistical considerations, reduced or lack of locally available
      resources and/or expertise. As a result, traditional approaches, including pulsed
      field gel electrophoresis, repetitive-element palindromic PCR and multilocus
      sequence typing, along with other typing methods, are still widely used. AIMS: To
      provide practitioners with evidenced-based action plans for usage of the various
      typing techniques in order to investigate the molecular epidemiology of
      nosocomial outbreaks, of clinically significant pathogens in acute-care
      hospitals. SOURCES: PubMed search with relevant keywords along with personal
      collection of relevant publications. CONTENT: Representative case scenarios and
      critical review of the relevant scientific literature. IMPLICATIONS: The review
      provides practical action plans to manage molecular epidemiologic investigations
      of outbreaks caused by clinically significant nosocomial pathogens, while
      prioritizing the use and timely integration of the various methodologies.

PMID- 30287414
TI  - Identification of Neisseria meningitidis by MALDI-TOF MS may not be reliable.
AB  - OBJECTIVES: The matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) technique is increasingly used in hospital
      laboratories for routine identification of microorganisms. However, its
      performance is variable, particularly for highly variable species such as
      Neisseria meningitidis. Reliable identification of N. meningitidis is crucial for
      the management of invasive meningococcal disease by rapid implementation of
      treatment and preventive measures among close contacts. We assessed and improved
      N. meningitidis identification by MALDI-TOF MS by enriching the databases with
      reference strains identified using whole genome sequencing (WGS) as a reference
      standard. METHODS: We first built a collection of 24 strains from several species
      of the Neisseria genus that we characterized by WGS. This collection was added to
      the available database to test by MALDI-TOF MS another collection of 32 clinical
      isolates received between 2015 and 2017 at the French National Reference
      Laboratory for Meningococci. RESULTS: Using the commercially available library of
      mass spectrometry profiles, only 67% (95% confidence interval (CI), 47-82)
      concordance was observed at the species level between MALDI-TOF MS and WGS
      characterization. However, when the new enriched reference collection was used on
      the second subset of isolates, the identification of N. meningitidis was
      significantly improved (p 0.0016), showing 92% (95% CI, 75-98) specificity while
      that of the manufacturer's database alone was 52% (95% CI, 34-70). CONCLUSIONS:
      Our data highlight the need to update the available MALDI-TOF MS database with
      high-quality references to enhance the identification of N. meningitidis and
      avoid unwarranted preventive measures or missing identification.

PMID- 30287415
TI  - Interaction and Engagement with an Anxiety Management App: Analysis Using Large
      Scale Behavioral Data.
AB  - BACKGROUND: SAM (Self-help for Anxiety Management) is a mobile phone app that
      provides self-help for anxiety management. Launched in 2013, the app has achieved
      over one million downloads on the iOS and Android platform app stores. Key
      features of the app are anxiety monitoring, self-help techniques, and social
      support via a mobile forum ("the Social Cloud"). This paper presents unique
      insights into eMental health app usage patterns and explores user behaviors and
      usage of self-help techniques. OBJECTIVE: The objective of our study was to
      investigate behavioral engagement and to establish discernible usage patterns of
      the app linked to the features of anxiety monitoring, ratings of self-help
      techniques, and social participation. METHODS: We use data mining techniques on
      aggregate data obtained from 105,380 registered users of the app's cloud
      services. RESULTS: Engagement generally conformed to common mobile participation
      patterns with an inverted pyramid or "funnel" of engagement of increasing
      intensity. We further identified 4 distinct groups of behavioral engagement
      differentiated by levels of activity in anxiety monitoring and social feature
      usage. Anxiety levels among all monitoring users were markedly reduced in the
      first few days of usage with some bounce back effect thereafter. A small group of
      users demonstrated long-term anxiety reduction (using a robust measure),
      typically monitored for 12-110 days, with 10-30 discrete updates and showed low
      levels of social participation. CONCLUSIONS: The data supported our expectation
      of different usage patterns, given flexible user journeys, and varying commitment
      in an unstructured mobile phone usage setting. We nevertheless show an aggregate
      trend of reduction in self-reported anxiety across all minimally-engaged users,
      while noting that due to the anonymized dataset, we did not have information on
      users also enrolled in therapy or other intervention while using the app. We find
      several commonalities between these app-based behavioral patterns and traditional
      therapy engagement.

PMID- 30287416
TI  - Designing a Patient Portal for Patient-Centered Care: Cross-Sectional Survey.
AB  - BACKGROUND: In recent literature, patient portals are considered as important
      tools for the delivery of patient-centered care. To date, it is not clear how
      patients would conceptualize a patient portal and which health information needs
      they have when doing so. OBJECTIVE: This study aimed (1) to investigate health
      information needs, expectations, and attitudes toward a patient portal and (2) to
      assess whether determinants, such as patient characteristics, health literacy,
      and empowerment status, can predict two different variables, namely the
      importance people attribute to obtaining health information when using a patient
      portal and the expectations concerning personal health care when using a patient
      portal. METHODS: We conducted a cross-sectional survey of the Flemish population
      on what patients prefer to know about their digital health data and their
      expectations and attitudes toward using a patient portal to access their
      electronic health record. People were invited to participate in the survey
      through newsletters, social media, and magazines. We used a questionnaire
      including demographics, health characteristics, health literacy, patient
      empowerment, and patient portal characteristics. RESULTS: We received 433
      completed surveys. The health information needs included features such as being
      notified when one's health changes (371/396, 93.7%), being notified when physical
      parameters increase to dangerous levels (370/395, 93.7%), observing connections
      between one's symptoms or diseases or biological parameters (339/398, 85.2%),
      viewing the evolution of one's health in function of time (333/394, 84.5%), and
      viewing information about the expected effect of treatment (349/395, 88.4%).
      Almost 90% (369/412) of respondents were interested in using a patient portal.
      Determinants of patients' attachment for obtaining health information on a
      patient portal were (1) age between 45 and 54 years (P=.05); (2) neutral (P=.03)
      or interested attitude (P=.008) toward shared decision making; and (3) commitment
      to question physicians' decisions (P=.03, R2=0.122). Determinants of patients'
      expectations on improved health care by accessing a patient portal were (1) lower
      education level (P=.04); (2) neutral (P=.03) or interested attitude (P=.008)
      toward shared decision making; and (3) problems in understanding health
      information (P=.04; R2=0.106). CONCLUSIONS: The interest in using a patient
      portal is considerable in Flanders. People would like to receive alerts or some
      form of communication from a patient portal in case they need to act to manage
      their health. Determinants such as education, attached importance to shared
      decision making, difficulties in finding relevant health information, and the
      attached importance in questioning the decisions of physicians need to be
      considered in the design of a patient portal.

PMID- 30287417
TI  - Identifying the Underlying Factors Associated With Patients' Attitudes Toward
      Antidepressants: Qualitative and Quantitative Analysis of Patient Drug Reviews.
AB  - BACKGROUND: Nonadherence to antidepressants is a major obstacle to deriving
      antidepressants' therapeutic benefits, resulting in significant burdens on the
      individuals and the health care system. Several studies have shown that
      nonadherence is weakly associated with personal and clinical variables but
      strongly associated with patients' beliefs and attitudes toward medications.
      Patients' drug review posts in online health care communities might provide a
      significant insight into patients' attitude toward antidepressants and could be
      used to address the challenges of self-report methods such as patients'
      recruitment. OBJECTIVE: The aim of this study was to use patient-generated data
      to identify factors affecting the patient's attitude toward 4 antidepressants
      drugs (sertraline [Zoloft], escitalopram [Lexapro], duloxetine [Cymbalta], and
      venlafaxine [Effexor XR]), which in turn, is a strong determinant of treatment
      nonadherence. We hypothesized that clinical variables (drug effectiveness;
      adverse drug reactions, ADRs; perceived distress from ADRs, ADR-PD; and duration
      of treatment) and personal variables (age, gender, and patients' knowledge about
      medications) are associated with patients' attitude toward antidepressants, and
      experience of ADRs and drug ineffectiveness are strongly associated with negative
      attitude. METHODS: We used both qualitative and quantitative methods to analyze
      the dataset. Patients' drug reviews were randomly selected from a health care
      forum called askapatient. The Framework method was used to build the analytical
      framework containing the themes for developing structured data from the
      qualitative drug reviews. Then, 4 annotators coded the drug reviews at the
      sentence level using the analytical framework. After managing missing values, we
      used chi-square and ordinal logistic regression to test and model the association
      between variables and attitude. RESULTS: A total of 892 reviews posted between
      February 2001 and September 2016 were analyzed. Most of the patients were females
      (680/892, 76.2%) and aged less than 40 years (540/892, 60.5%). Patient attitude
      was significantly (P<.001) associated with experience of ADRs, ADR-PD, drug
      effectiveness, perceived lack of knowledge, experience of withdrawal, and
      duration of usage, whereas oth age (F4,874=0.72, P=.58) and gender (chi24=2.7,
      P=.21) were not found to be associated with patient attitudes. Moreover, modeling
      the relationship between variables and attitudes showed that drug effectiveness
      and perceived distress from adverse drug reactions were the 2 most significant
      factors affecting patients' attitude toward antidepressants. CONCLUSIONS:
      Patients' self-report experiences of medications in online health care
      communities can provide a direct insight into the underlying factors associated
      with patients' perceptions and attitudes toward antidepressants. However, it
      cannot be used as a replacement for self-report methods because of the lack of
      information for some of the variables, colloquial language, and the unstructured
      format of the reports.

PMID- 30287418
TI  - microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and
      knee joints.
AB  - OBJECTIVES: We recently identified microRNA-181a-5p (miR-181a-5p) as a critical
      mediator involved in the destruction of lumbar facet joint (FJ) cartilage. In
      this study, we tested if locked nucleic acid (LNA) miR-181a-5p antisense
      oligonucleotides (ASO) could be used as a therapeutic to limit articular
      cartilage degeneration. METHODS: We used a variety of experimental models
      consisting of both human samples and animal models of FJ and knee osteoarthritis
      (OA) to test the effects of LNA-miR-181a-5p ASO on articular cartilage
      degeneration. Histopathological analysis including immunohistochemistry and in
      situ hybridisation were used to detect key OA catabolic markers and microRNA,
      respectively. Apoptotic/cell death markers were evaluated by flow cytometry. qPCR
      and immunoblotting were applied to quantify gene and protein expression. RESULTS:
      miR-181a-5p expression was increased in human FJ OA and knee OA cartilage as well
      as injury-induced FJ OA (rat) and trauma-induced knee OA (mouse) cartilage
      compared with control cartilage, correlating with classical OA catabolic markers
      in human, rat and mouse cartilage. We demonstrated that LNA-miR-181a-5p ASO in
      rat and mouse chondrocytes reduced the expression of cartilage catabolic and
      chondrocyte apoptotic/cell death markers in vitro. Treatment of OA-induced rat FJ
      or mouse knee joints with intra-articular injections of in vivo grade LNA-miR
      181a-5p ASO attenuated cartilage destruction, and the expression of catabolic,
      hypertrophic, apoptotic/cell death and type II collagen breakdown markers.
      Finally, treatment of LNA-miR-181a-5p ASO in cultures of human knee OA
      chondrocytes (in vitro) and cartilage explants (ex vivo) further demonstrated its
      cartilage protective effects. CONCLUSIONS: Our data demonstrate, for the first
      time, that LNA-miR-181a-5p ASO exhibit cartilage-protective effects in FJ and
      knee OA.

PMID- 30287420
TI  - Right time, right place-DNA damage and DNA replication checkpoints collectively
      safeguard S phase.

PMID- 30287421
TI  - The RECK tumor-suppressor protein binds and stabilizes ADAMTS10.
AB  - The tumor suppressor protein RECK has been implicated in the regulation of matrix
      metalloproteinases (MMPs), NOTCH-signaling and WNT7-signaling. It remains
      unclear, however, how broad the spectrum of RECK targets extends. To find novel
      RECK binding partners, we took the unbiased approach of yeast two-hybrid
      screening. This approach detected ADAMTS10 as a RECK-interactor. ADAMTS10 has
      been characterized as a metalloproteinase involved in fibrillin-rich microfibril
      biogenesis, and its mutations have been implicated in the connective tissue
      disorder Weill-Marchesani syndrome. Experiments in vitro using recombinant
      proteins expressed in mammalian cells indicated that RECK indeed binds ADAMTS10
      directly, that RECK protects ADAMTS10 from fragmentation following chemical
      activation and that ADAMTS10 interferes with the activity of RECK to inhibit MT1
      MMP. In cultured cells, RECK increases the amount of ADAMTS10 associated with the
      cells. Hence, the present study has uncovered novel interactions between two
      molecules of known clinical importance, RECK and ADAMTS10.This article has an
      associated First Person interview with the first author of the paper.

PMID- 30287423
TI  - The Bawa-Garba principle for medical error.

PMID- 30287422
TI  - Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes: The EASE
      Trials.
AB  - OBJECTIVE: To evaluate the safety and efficacy of empagliflozin 10- and 25-mg
      doses plus a unique lower dose (2.5 mg) as adjunct to intensified insulin in
      patients with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: The EASE
      (Empagliflozin as Adjunctive to inSulin thErapy) program (N = 1,707) included two
      double-blind, placebo-controlled phase 3 trials: EASE-2 with empagliflozin 10 mg
      (n = 243), 25 mg (n = 244), and placebo (n = 243), 52-week treatment; and EASE-3
      with empagliflozin 2.5 mg (n = 241), 10 mg (n = 248), 25 mg (n = 245), and
      placebo (n = 241), 26-week treatment. Together they evaluated empagliflozin 10 mg
      and 25 mg, doses currently approved in treatment of type 2 diabetes, and
      additionally 2.5 mg on 26-week change in glycated hemoglobin (primary end point)
      and weight, glucose time-in-range (>70 to <=180 mg/dL), insulin dose, blood
      pressure, and hypoglycemia. RESULTS: The observed largest mean placebo-subtracted
      glycated hemoglobin reductions were -0.28% (95% CI -0.42, -0.15) for 2.5 mg, 
      0.54% (-0.65, -0.42) for 10 mg, and -0.53% (-0.65, -0.42) for 25 mg (all P <
      0.0001). Empagliflozin 2.5/10/25 mg doses, respectively, reduced mean weight by 
      1.8/-3.0/-3.4 kg (all P < 0.0001); increased glucose time-in-range by
      +1.0/+2.9/+3.1 h/day (P < 0.0001 for 10 and 25 mg); lowered total daily insulin
      dose by -6.4/-13.3/-12.7% (all P < 0.0001); and decreased systolic blood pressure
      by -2.1/-3.9/-3.7 mmHg (all P < 0.05). Genital infections occurred more
      frequently on empagliflozin. Adjudicated diabetic ketoacidosis occurred more with
      empagliflozin 10 mg (4.3%) and 25 mg (3.3%) but was comparable between
      empagliflozin 2.5 mg (0.8%) and placebo (1.2%). Severe hypoglycemia was rare and
      frequency was similar between empagliflozin and placebo. CONCLUSIONS:
      Empagliflozin improved glycemic control and weight in T1D without increasing
      hypoglycemia. Ketoacidosis rate was comparable between empagliflozin 2.5 mg and
      placebo but increased with 10 mg and 25 mg. Ketone monitoring for early
      ketoacidosis detection and intervention and lower empagliflozin doses may help to
      reduce this risk.

PMID- 30287425
TI  - The challenge of change: evidence, culture and expertise.

PMID- 30287426
TI  - A virtual clinic to improve long-term outcomes in chronic kidney disease.
AB  - Chronic kidney disease (CKD) is common. A small proportion of patients with CKD
      progress to require interventions, which may include dialysis. Monitoring
      patients with CKD is supported by national guidelines. Monitoring systems to plan
      management of CKD vary in form. A novel monitoring system, the virtual CKD clinic
      (VC) was introduced at our hospital. The VC is a non-face-to-face results review
      of patients with CKD. We found that the VC was an effective monitoring system.
      None of the patients from the VC required emergency dialysis, suggesting robust
      surveillance. Survival was similar to patients with CKD discharged to primary
      care.

PMID- 30287424
TI  - Acute Kidney Injury among Hospitalized Children in China.
AB  - BACKGROUND AND OBJECTIVES: High-quality epidemiologic data on AKI in children are
      particularly lacking in developing countries. This study aimed to assess the
      epidemiology and clinical correlates of AKI among hospitalized children in China.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a multicenter study,
      in a cohort of hospitalized children aged 1 month to 18 years, from 25 general
      and children's hospitals in China during 2013-2015. We obtained patient-level
      data from the electronic hospitalization information system and laboratory
      databases of all children who had at least two serum creatinine tests within any
      7-day window during their first 30 days of hospitalization. We identified AKI
      events according to the creatinine criteria of Kidney Disease Improving Global
      Outcomes. The in-hospital outcomes of AKI, including mortality, kidney recovery,
      and length of stay, were assessed. We estimated the corresponding hazard ratios
      using a Cox proportional hazard model, with adjustment for age, sex,
      comorbidities, and clinical procedures. RESULTS: A total of 19,908 (20%) patients
      with AKI were identified among 101,836 pediatric inpatients, of which 7220 (7%)
      were community acquired and 12,688 (13%) were hospital acquired. Up to 96% of
      these AKI events were not diagnosed on the discharge records. The cumulative
      incidence of AKI in infants (28%) was twice that in adolescents (12%). The
      profiles of risk factors differed between community-acquired and hospital
      acquired AKI and varied with age. Diarrhea and sepsis were the top risk factors
      for community-acquired AKI, each contributing 6% of the risk. Congenital heart
      disease/cardiac surgery was the major risk factor for hospital-acquired AKI,
      contributing to 19% of cases. Exposure to nephrotoxic drugs, mostly nonsteroidal
      anti-inflammatory drugs and proton pump inhibitors, was common in hospitalized
      children and was associated with a higher risk of AKI. Death occurred in 842 out
      of 19,908 patients (4%) with AKI versus 450 out of 81,478 children (0.5%) without
      AKI. The risk of in-hospital death was higher among children with severe AKI,
      shock, and respiratory failure. Pediatric AKI was associated with longer hospital
      stay and higher daily cost, even after adjustment for covariates. CONCLUSIONS:
      Pediatric AKI is common and is substantially underdiagnosed in China.

PMID- 30287428
TI  - NEWS 2 - too little evidence to implement?
AB  - The Royal College of Physicians (RCP) recently published the National Early
      Warning Score 2 (NEWS2), aiming to improve safety for patients with hypercapnic
      respiratory failure by suggesting a separate oxygen saturation (SpO2) parameter
      scoring system for such patients. A previously published study of patients
      (n=2,361 admissions) with acute exacerbation of chronic obstructive pulmonary
      disease (AECOPD) demonstrated alternative scoring systems at admission did not
      outperform the original NEWS. Applying NEWS2 SpO2 parameters to this previously
      described cohort would have resulted in 44% (n=27/62) of patients who scored >=7
      points on the original NEWS and subsequently died being placed in a lower call
      out threshold. NEWS2 loses the benefits of a unified, standardised scoring system
      and we suggest prospective research in this area before applying this adjustment.

PMID- 30287427
TI  - Immunoglobulin use in immune deficiency in the UK: a report of the UKPID and
      National Immunoglobulin Databases.
AB  - Supply of immunoglobulin in the UK faces pressures due to increasing demand, cost
      and variable supply. This paper describes immunoglobulin replacement therapy
      (IGRT) in primary immunodeficiency (PID) and secondary immunodeficiency (SID) to
      assist in the ongoing planning of UK immunoglobulin provision. A retrospective
      analysis of the National Immunoglobulin Database and the UKPID registry was
      carried out. In total, 3,222 patients are registered as receiving IGRT for
      immunodeficiencies. Predominately antibody disorders made up the largest
      diagnostic category (61% of patients). The total cost of IGRT for
      immunodeficiency for 2015/16 was L40,673,350; an average annual cost of
      L1,099,254 per centre and L12,124 per PID patient. SCIg accounted for 43.8% and
      50.1% of IGRT, with home therapy accounting for 42.7% and 57.5% of place of
      therapy in the National Immunoglobulin Database and UKPID registry respectively.
      In 2015/16 use of immunoglobulin in SID increased by 24% over the previous
      financial year. The overall trends of increasing demand in immunology are
      mirrored in other specialties, most notably neurology and haematology. These data
      are the first national overview of IGRT for immunodeficiencies, providing a
      valuable resource for clinicians and policy makers in the ongoing management of
      UK immunoglobulin supply.

PMID- 30287429
TI  - Are we on the same page? Exploring the role of the geriatrician in the care of
      the older surgical patient from the perspective of surgeons and geriatricians.
AB  - There is increasing recognition that the ageing population represents a challenge
      to existing surgical services. National reports recommend that geriatricians
      proactively review older surgical patients to improve care and outcomes. However,
      this approach has not been widely translated into practice. A qualitative study
      was conducted using 12 semi-structured interviews of surgeons and geriatricians
      to explore the role of the geriatrician in the care of older surgical patients.
      Participants agreed that the current system did not meet the needs of older
      surgical patients. Geriatricians valued their holistic way of working but these
      generalist skills can overlap with other specialties, seen by some as wasting
      resources. Three models of care were proposed, with the ownership and location of
      the patient as well as the role of education being the key variables. The main
      obstacle preventing integrated working was the concern of de-skilling the
      surgeons, narrowing their role to that of a 'technician'. Other barriers included
      loss of autonomy; lack of evidence; and a lack of recognition of the need for a
      geriatrician. There is acceptance that closer working practices are necessary to
      meet the needs of this complex patient group but a lack of evidence, together
      with significant human factors, are challenges that must be addressed to realise
      this aim.

PMID- 30287430
TI  - The British Army's contribution to tropical medicine.
AB  - Infectious disease has burdened European armies since the Crusades. Beginning in
      the 18th century, therefore, the British Army has instituted novel methods for
      the diagnosis, prevention and treatment of tropical diseases. Many of the
      diseases that are humanity's biggest killers were characterised by medical
      officers and the acceptance of germ theory heralded a golden era of discovery and
      development. Luminaries of tropical medicine including Bruce, Wright, Leishman
      and Ross firmly established the British Army's expertise in this area. These
      innovations led to the prevention of many deaths of both military personnel and
      civilians. British Army doctors were instrumental in establishing many of the
      teaching facilities that we now consider to be global leaders in tropical
      medicine. The impact of the Army in this field has certainly been significant in
      the past and its contribution continues to this day.

PMID- 30287431
TI  - Acute kidney injury and 'nephrotoxins': mind your language.
AB  - The introduction of the term 'acute kidney injury' (AKI) along with an
      international classification scheme,1 caused some initial confusion, but most
      clinicians and many patients now understand that the term 'injury' denotes damage
      to the internal workings of the kidney, rather than physical trauma. However, of
      greater concern is the use of the term 'nephrotoxic' to include drugs that are,
      in most settings, nephroprotective. We argue that this imprecise terminology,
      unfortunately adopted by the National Institute for Health and Care Excellence
      (NICE) among others, is potentially harmful, and that the terms 'nephrotoxin' and
      'nephrotoxic' should not be used to describe haemodynamically mediated and fully
      reversible effects of some drugs on excretory function.

PMID- 30287432
TI  - An update on the use of inhaled therapy in COPD.
AB  - Inhaled corticosteroids represent the mainstay of pharmacological treatment for
      reversible airways disease, and traditionally have had widespread use in non
      reversible chronic obstructive pulmonary disease (COPD). However, use in this
      group may expose patients to an increased risk of pneumonia, without significant
      benefit to symptoms or exacerbation frequency. Here we provide a guide to the use
      of inhaled therapy in COPD for the general physician.

PMID- 30287433
TI  - What is the significance of monoclonal gammopathy of undetermined significance?
AB  - Monoclonal gammopathy of undetermined significance (MGUS) is characterised by the
      presence of a monoclonal paraprotein in the blood, without the characteristic end
      organ damage seen in multiple myeloma. MGUS is more common in older age groups
      and has a risk of progression to myeloma of 1% per year. Population screening is
      not currently recommended, but retrospective studies have suggested improvements
      in myeloma outcomes in those under MGUS follow-up; in addition, MGUS has
      associated complications, including fracture, osteoporosis, renal disease and
      infection, which can be treated. Given this increasing evidence of disease
      related directly to MGUS, strategies for early identification might be needed. In
      this review, we discuss the complications of MGUS and whether MGUS fulfils the
      criteria needed to implement a screening programme. We also highlight areas where
      more evidence is needed, including identification of a higher risk population to
      make screening more practical and economically viable.

PMID- 30287434
TI  - Later careers - regenerating the medical workforce.
AB  - We have a medical workforce crisis where we have insufficient trainees,
      demonstrated by rota gaps, and in turn nearly half of advertised consultant
      physician posts cannot be appointed to. Most physicians retire around age 62, and
      already 5% of the total consultant workforce is those who have retired and
      returned. If those reaching retirement age chose not to retire but continue
      working less than full time this would, at least in part, benefit the workforce
      and utilise valuable skills and experience to the benefit of the individual, the
      wider medical community and therefore our patients.

PMID- 30287435
TI  - An old disease re-emerging: acute rheumatic fever.
AB  - We present the case of a 41-year-old Australian woman with a 3-day history of
      fevers and migratory polyarthritis. Three weeks prior she had been treated by her
      GP with phenoxymethylpenicillin for acute tonsillitis. Examination confirmed
      synovitis. Systemic assessment including cardiovascular, neurological and skin
      examination was unremarkable. Abnormal investigations included a leucocytosis
      with neutrophilia, C-reactive peptide of 116 mg/L, erythrocyte sedimentation rate
      of 103 mm/hour and acute transaminitis. The antistreptolysin O titre was 304 IU,
      which increased to 1,250 IU after 2 weeks. Troponin T, electrocardiogram and
      echocardiography were all normal. The patient was treated for acute rheumatic
      fever with corticosteroids and a 10-day course of cephalexin. After 8 weeks, she
      made a full recovery and had normalised inflammatory markers and liver
      biochemistry. She was then commenced on monthly prophylactic intramuscular
      benzathine penicillin. This case study aims to raise awareness of the
      presentation, diagnosis and management of acute rheumatic fever.

PMID- 30287436
TI  - Pneumomediastinum complicating adult-onset measles.
AB  - Adult-onset measles is rare in the UK, particularly in patients with a complete
      vaccination history.We present a case of a UK-born patient who received all
      childhood vaccinations, had no history of recent travel or unwell contacts who
      was diagnosed with measles complicated by pneumomediastinum. This case highlights
      the need to consider measles in any patient presenting with a constellation of a
      macular rash, fever and conjunctivitis, regardless of vaccination status. The
      nature of the rash can provide an important clue to the diagnosis. Liaison with
      infection specialists facilitates early diagnosis, allowing for appropriate
      initial investigations, improving clinical management and early infection control
      precautions being instituted.

PMID- 30287437
TI  - Spontaneous splenic rupture secondary to dabigatran: the last in a series of
      unfortunate events.
AB  - We present the case of a 77-year-old woman who had an accidental fall in her
      garden, resulting in a fracture of her left ankle. After manipulation of the
      fracture, she developed sudden onset shortness of breath. An echo led to the
      diagnosis of Takotsubo cardiomyopathy. Shortly after this she developed sudden
      onset receptive and expressive dysphasia. Magnetic resonance imaging (MRI) of the
      head confirmed a left parietal infarct thought to be secondary to left
      ventricular thrombus formation. She was started on dabigatran. A few days later,
      she developed abdominal pain, and was subsequently diagnosed with a spontaneous
      splenic rupture. This case was interesting due to the unusual chain of events
      following a simple fall, and also a rare complication of anticoagulant therapy.

PMID- 30287438
TI  - Seizures and epilepsy in the acute medical setting: presentation and management.
AB  - Epileptic seizures are a common cause for presentation to acute medical services.
      Whether presenting with an isolated, unprovoked seizure or with status
      epilepticus, a good understanding of seizures and their mimics ensures
      appropriate investigation and treatment. This article describes the practical
      aspects of the management of patients presenting with seizures to the emergency
      department or the acute medical unit.

PMID- 30287439
TI  - Functional neurological disorders: acute presentations and management.
AB  - Functional neurological disorders (FND) are common and associated with
      significant morbidity and healthcare costs. Patients with FND often present
      acutely, particularly with dissociative seizures (resembling epilepsy) or
      persistent weakness resembling a stroke. History and careful observation and
      examination are critical to diagnosis, as investigations will often be normal or
      non-contributory. The nature of convulsive movements in dissociative seizures
      often differs from that in epilepsy, and long duration of individual events,
      waxing and waning, closed eyes and high reported frequency in an apparently well
      individual are all suggestive. In those with stroke-like episodes, demonstration
      of normal power even briefly (eg Hoover's sign, 'give way' weakness) together
      with distractability are positive physical features indicating a functional
      disorder. A positive diagnosis and clear non-judgemental explanation, backed up
      by reliable information sources associated with prompt onward referral to a
      neurologist can greatly reduce distress and ultimately improve outcomes.

PMID- 30287441
TI  - Assessment of acute headache in adults - what the general physician needs to
      know.
AB  - Headache is common. Up to 5% of attendances to emergency departments and acute
      medical units are due to headache. Headache is classified as either primary (eg
      migraine, cluster headache) or secondary to another cause (eg meningitis,
      subarachnoid haemorrhage). Even in the acute setting the majority of cases are
      due to primary causes. The role of the attending physician is to take a
      comprehensive history to diagnose and treat benign headache syndromes while
      ruling out sinister aetiologies. This brief article summarises the approach to
      assessment of headache presenting in acute and emergency care.

PMID- 30287440
TI  - Acute neurology: a suggested approach.
AB  - Acute neurological problems are common, accounting for 10-20% of medical
      admissions. In the coming years, there will be increased neurology involvement in
      the acute care of these patients complementing traditional outpatient-based
      services. Models of acute neurology are reliant on close collaboration between
      the emergency department, acute medicine and neurology and should integrate with
      existing hyperacute stroke pathways. In this article the authors briefly describe
      the two models of acute neurology set up recently in our neuroscience group and
      suggest a clinical approach that may help non-neurologists involved in acute care
      settings. The authors emphasise some of the lessons learnt in delivering the
      service, particularly the importance of focusing on the acute problem and
      tailoring the examination and investigations to tackling it in the context of the
      patient's functional level and personal circumstances. Early neurology
      intervention can reduce admission and hospital length of stay.

PMID- 30287443
TI  - Lesson of the month 1: Sodium valproate-induced encephalopathy.
AB  - A 69-year-old man developed reduced consciousness of sudden onset. Examination
      and parameters were normal, except for a Glasgow Coma Scale (GCS) score of six.
      Brain imaging and blood tests were also normal, except for high plasma ammonia.
      His past medical history included epilepsy, hypertension and colitis. He was
      taking multiple antiepileptic medications, including sodium valproate, with no
      recent dose alterations. Medical intervention led to the sodium valproate being
      stopped and naloxone being administered. The patient's level of responsiveness
      and ammonia levels gradually improved. The patient was also being treated with
      ciprofloxacin for a urinary tract infection and a newly developed syndrome of
      inappropriate antidiuretic hormone secretion treated with demeclocycline. There
      is an association between long-term sodium valproate use and low carnitine
      levels, especially in the setting of polypharmacy. This in turn precipitates
      hyperammonaemia and encephalopathy. This case highlights the importance of an
      adequate drug history and the awareness of serious but uncommon adverse effects.

PMID- 30287442
TI  - CME Neurology (120487): self-assessment questionnaire.

PMID- 30287444
TI  - Lesson of the month 2: An unusual cause of depression in an older man: Cushing's
      syndrome resulting from metastatic small cell cancer of the prostate.
AB  - This article describes the case of an older patient whose main presenting problem
      was depression. A constellation of clinical and biochemical features led to a
      search for medical causes of his low mood, which uncovered ectopic
      adrenocorticotropic hormone (ACTH) secretion. Post-mortem examination showed that
      the source of ACTH was small cell neuroendocrine carcinoma of the prostate, and
      that the patient had died from the sequelae of profound immune suppression.

PMID- 30287445
TI  - Image of the month: Brachiocephalic arterial occlusive limb-shaking transient
      ischaemic attacks.

PMID- 30287447
TI  - Bawa-Garba case: an objective view on diagnosing group A streptococcal sepsis.

PMID- 30287446
TI  - Patient power - Kidd Gloves.

PMID- 30287448
TI  - Vitamin D testing: the British Society for Rheumatology's Choosing Wisely
      recommendations.

PMID- 30287449
TI  - Vitamin E - a cause for concern?

PMID- 30287450
TI  - Response.

PMID- 30287451
TI  - Gardening injuries.

PMID- 30287452
TI  - Should point-of-care ultrasound be in the new internal medicine curriculum?

PMID- 30287453
TI  - Seven days in medicine: 26 September to 2 October 2018.

PMID- 30287454
TI  - Reply.

PMID- 30287455
TI  - Do All Patients with Multiple Sclerosis Benefit from the Use of Contrast on
      Serial Follow-Up MR Imaging? A Retrospective Analysis.
AB  - BACKGROUND AND PURPOSE: Patients with multiple sclerosis routinely have MR
      imaging with contrast every 6-12 months to assess response to medication.
      Multiple recent studies provide evidence of tissue deposition of MR imaging
      contrast agents, questioning the long-term safety of these agents. The goal of
      this retrospective image-analysis study was to determine whether contrast could
      be reserved for only those patients who show new MS lesions on follow-up
      examinations. MATERIALS AND METHODS: We retrospectively reviewed brain MRIs of
      138 patients. To increase our sensitivity, we used a previously described
      computerized image-comparison software to evaluate the stability or progression
      of multiple sclerosis white matter lesions in noncontrast FLAIR sequences. We
      correlated these findings with evidence of contrast-enhancing lesions on the
      enhanced T1 sequence from the same scan. RESULTS: Thirty-three scans showed an
      increase in white matter lesion burden. Among those 33 patients, 14 examinations
      also demonstrated enhancing new lesions. While we found a single example of
      enhancement of a pre-existing white matter lesion that appeared unchanged in
      size, that same examination showed an overall increase in lesion burden with
      enhancement of other, new lesions. Thus, we found that all patients with
      enhancing lesions had evidence of progression on their noncontrast imaging.
      CONCLUSIONS: Because all enhancing lesions were associated with new lesions on
      unenhanced imaging and progression was only evident in 24% of patients, in
      patients with relapsing-remitting MS, it is reasonable to consider reserving
      contrast for only those patients with evidence of progression on noncontrast MR
      images.

PMID- 30287457
TI  - Reply.

PMID- 30287456
TI  - Impact of Ischemic Lesion Location on the mRS Score in Patients with Ischemic
      Stroke: A Voxel-Based Approach.
AB  - BACKGROUND AND PURPOSE: Previous studies indicated that ischemic lesion volume
      might be a useful surrogate marker for functional outcome in ischemic stroke but
      should be considered in the context of lesion location. In contrast to previous
      studies using the ROI approach, which has several drawbacks, the present study
      aimed to measure the impact of ischemic lesion location on functional outcome
      using a more precise voxelwise approach. MATERIALS AND METHODS: Datasets of
      patients with acute ischemic strokes from the Multicenter Randomized Clinical
      Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands (MR
      CLEAN) were used. Primary outcome was functional outcome as assessed by the
      modified Rankin Scale 3 months after stroke. Ischemic lesion volume was
      determined on CT scans 3-9 days after stroke. Voxel-based lesion-symptom mapping
      techniques, including covariates that are known to be associated with functional
      outcome, were used to determine the impact of ischemic lesion location for
      outcome. RESULTS: Of the 500 patients in the MR CLEAN trial, 216 were included
      for analysis. The mean age was 63 years. Lesion-symptom mapping with inclusion of
      covariates revealed that especially left-hemispheric lesions in the deep
      periventricular white matter and adjacent internal capsule showed a great
      influence on functional outcome. CONCLUSIONS: Our study confirms that infarct
      location has an important impact on functional outcome of patients with stroke
      and should be considered in prediction models. After we adjusted for covariates,
      the left-hemispheric corticosubcortical fiber tracts seemed to be of higher
      functional importance compared with cortical lesions.

PMID- 30287458
TI  - Spinal Coccidioidomycosis: MR Imaging Findings in 41 Patients.
AB  - BACKGROUND AND PURPOSE: Coccidioides immitis is a dimorphic fungus endemic to the
      Southwest United States and Mexico, and at our institution, it is a relatively
      common pathogen presenting with a broad spectrum of associated spine diseases. We
      describe the various spinal manifestations resulting from coccidioidal infection
      and provide MR imaging examples from 41 pathologically proved cases. MATERIALS
      AND METHODS: Retrospective electronic medical record and PACS searches were
      performed. Patients found to have both MR imaging findings positive for infection
      and confirmative biopsy and/or CSF studies were included. Abnormal MR imaging
      findings were identified, categorized, and quantified. Patient demographics and
      associated intracranial involvement if present were also recorded. RESULTS: Forty
      one patients were included. Positive findings were categorized as leptomeningeal
      enhancement (26 patients, 63%), arachnoiditis (22 patients, 54%), osteomyelitis
      discitis (14 patients, 34%), cord edema (11 patients, 27%), and true syrinx (3
      patients, 7%). Thirty patients had documented brain involvement (73%), most
      commonly in the form of basilar meningitis. Four patients were positive for HIV
      (10%). Fifteen patients had pulmonary manifestations at presentation (37%).
      CONCLUSIONS: C immitis results in various spinal manifestations, most commonly
      leptomeningeal enhancement and arachnoiditis/adhesive disease followed by
      osteomyelitis, which may resemble tuberculous or pyogenic infection on MR
      imaging.

PMID- 30287459
TI  - Flow-Diversion Effect of LEO Stents: Aneurysm Occlusion and Flow Remodeling of
      Covered Side Branches and Perforators.
AB  - BACKGROUND AND PURPOSE: Flow diversion with intermediate-porosity stents (braided
      stents) has been recently reported for distally located small aneurysms. The aim
      of this study was to evaluate the flow-diversion effect of LEO stents on covered
      vessels and for aneurysms treated with sole stent-placement therapy. MATERIALS
      AND METHODS: We retrospectively evaluated the following outcomes: 1) remodeling
      of covered side branches and perforators (extra-aneurysmal flow remodeling), and
      2) the occlusion rate of aneurysms treated with sole stent-placement therapy
      (intra-aneurysmal flow remodeling). RESULTS: Seventy-six patients with 98 covered
      vessels were studied. Overall, 89 covered arteries (91%) were normal, 7 showed
      narrowing (7%), and 2 (2%) were occluded (1 posterior communicating artery and 1
      MCA) without related complications (mean DSA follow-up, 14 months). Univariate
      and multivariate analyses highlighted smoking (P = .03) and the length of follow
      up (P = .002) as factors associated with arterial remodeling. Of the 17 Sylvian
      (lenticulostriate arteries) and 7 basilar perforators, 1 (4%) group of Sylvian
      perforators covered with double stents had asymptomatic remodeling. Ten aneurysms
      (mean size, 3.5 mm) were treated with LEO stents as stent monotherapy (5
      recanalized after coiling and 5 directly treated with the LEO). Complete
      occlusion (Raymond-Roy I) was achieved in 70% of aneurysms (mean follow-up, 14
      months). The Raymond-Roy I occlusion rate among recanalized aneurysms and those
      directly treated with LEO stents was 80% and 60%, respectively (P = .9).
      CONCLUSIONS: The rate of flow remodeling on the covered arteries and perforators
      was 9% and 4%, respectively, and was clinically irrelevant in all cases. Complete
      occlusion of aneurysms treated with sole stent-placement therapy was 70%. These
      data stress the flow-diversion properties of LEO stents.

PMID- 30287461
TI  - Fluoroscopically Guided Facet Injections: Comparison of Intra-Articular and
      Periarticular Steroid and Anesthetic Injection on Immediate and Short-Term Pain
      Relief.
AB  - BACKGROUND AND PURPOSE: The effectiveness of facet injections is unclear in the
      literature. Our objective was to determine the immediate and short-term efficacy
      of intra-articular and periarticular steroid/anesthetic injections for facet
      mediated lumbar pain. MATERIALS AND METHODS: All outpatient fluoroscopically
      guided facet injections at a single institution during a 54-month period were
      retrospectively and independently reviewed by 2 musculoskeletal (MSK) trained
      radiologists. All intra-articular, all periarticular, and partial intra
      /periarticular injection locations were determined. Periarticular and partial
      peri-/intra-articular injections were combined for analysis. Preinjection,
      immediate, and 1-week postinjection numeric pain scores, patient age, sex,
      anesthetic/steroid mixture, fluoroscopic time, and physician performing the
      procedure were recorded. RESULTS: Seventy-seven patients (mean age, 51.1 years)
      had 100 procedures with 205 total facet joints injected. All intra-articular, all
      periarticular, and partial peri-/intra-articular injections constituted 54%, 20%,
      and 26% of the cases, respectively. The immediate and 1-week postprocedural
      change in pain was -3.7 (95% CI, -4.5 to -2.8; P < .001) and -1.4 (95% CI, -2.2
      to -0.6; P = .001) for the all intra-articular and -3.6 (95% CI, -4.4 to -2.9; P
      < .001) and -1.2 (95% CI, -1.9 to -0.4; P = .002) for the combined group. Changes
      in immediate pain were significantly associated with the prepain level (P < .001)
      and patient age (P = .024) but not with the anesthetic used. Analyses revealed no
      significant difference in pain reduction between the groups either immediately or
      1 week postinjection. Intra-articular injections required less fluoroscopic time
      (geometric mean, 39 versus 52 seconds) (P = .005). CONCLUSIONS: Intra-articular
      and periarticular fluoroscopically guided facet injections provide statistically
      significant and similar pain relief both immediately and 1 week postinjection.

PMID- 30287460
TI  - Subtraction CTA: An Alternative Imaging Option for the Follow-Up of Flow-Diverter
      Treated Aneurysms?
AB  - BACKGROUND AND PURPOSE: This was a pilot study to explore the diagnostic accuracy
      and safety of subtraction CTA combined with a single-energy metal artifact
      reduction algorithm (SEMAR) compared to DSA for the evaluation of intracranial
      aneurysm occlusion after flow diverter treatment. MATERIALS AND METHODS: We
      included patients treated with a flow diverter for an unruptured intracranial
      aneurysm between November 2015 and November 2016. The patient cohort comprised 2
      groups: those who underwent follow-up imaging 1 month after flow-diverter
      treatment and those with a known residual intracranial aneurysm after flow
      diverter treatment who underwent imaging at regular follow-ups. Full-brain
      subtraction CTA was performed on a 320-detector row CT system. A low-dose non
      enhanced volume acquisition was followed by a contrast-enhanced volume CTA.
      Iterative and noise-reduction filters, SEMAR, and SURESubtraction algorithms were
      applied. DSA was performed on a flat panel C-arm angiography system. Standard
      posteroanterior, lateral, 3D, and detailed 2D acquisitions were performed.
      Imaging was independently scored by 2 clinicians. Aneurysm occlusion (Raymond
      scale) was our primary outcome parameter. RESULTS: Thirteen intracranial
      aneurysms were evaluated with subtraction CTA and DSA. Nine aneurysm remnants
      were demonstrated by both subtraction CTA and DSA. The sensitivity and
      specificity of subtraction CTA for the detection of aneurysm occlusion were 100%
      (95% CI, 82.41%-100%) and 100% (95% CI, 67.55%-100%), respectively. Agreement
      between readers was perfect (kappa = 1.0). The smallest neck remnant detected on
      subtraction CTA was 1.2 mm. No complications occurred. CONCLUSIONS: Subtraction
      CTA with single-electron metal artifact reduction is effective in the reduction
      of metal artifacts of flow diverters and might therefore be a viable alternative
      in the assessment of intracranial aneurysm occlusion after flow diverter
      treatment.

PMID- 30287462
TI  - Methodologic Issues on Interrater Reliability Regarding Structural and DTI-Based
      Corticospinal Tract Asymmetry.

PMID- 30287463
TI  - Vessel Wall Enhancement in Treated Unruptured Aneurysms.

PMID- 30287464
TI  - RCGP chair refutes tech companies claims that GPs are "technophobic dinosaurs".

PMID- 30287465
TI  - A long sought after "receptor" for ERFE?

PMID- 30287467
TI  - Next-generation therapy for follicular lymphoma.

PMID- 30287466
TI  - M-protein-related disorders: MGCS.

PMID- 30287468
TI  - Getting the most from your CAR target.

PMID- 30287469
TI  - MBD4: guardian of the epigenetic galaxy.

PMID- 30287470
TI  - Mice no longer immune to immunomodulatory drugs.

PMID- 30287471
TI  - An unexpected association of hematologic malignancies.

PMID- 30287472
TI  - Obstructive sleep apnoea as a risk factor for incident metabolic syndrome: a
      joined Episono and HypnoLaus prospective cohorts study.
AB  - Cross-sectional studies have demonstrated that obstructive sleep apnoea (OSA) and
      metabolic syndrome (MetS) are often associated, but whether a temporal
      relationship exists is unknown. We aimed to investigate the effect of OSA on the
      risk of developing MetS in the general population.A prospective study was
      conducted combining two population-based samples: Episono (Brazil) and HypnoLaus
      (Switzerland). MetS was assessed according to unified criteria. Polysomnography
      (PSG) was performed at baseline and follow-up in Episono, and at baseline in
      HypnoLaus. OSA was defined according to the apnoea-hypopnoea index as mild (>=5-
      <15 events h-1) and moderate-to-severe (>=15 events.h-1). We included 1853
      participants (mean+/-sd age 52+/-13 years, 56% female) without MetS at
      baseline.After mean+/-sd 6+/-1 years, 318 (17.2%) participants developed MetS.
      Moderate-to-severe OSA was independently associated with incident MetS (OR 2.58,
      95% CI 1.61-4.11) and increased the number of MetS components from baseline to
      follow-up through mediation of the percentage of time with arterial oxygen
      saturation <90%. Subset analysis in Episono confirmed that the increase in this
      parameter between baseline and follow-up PSGs represented a risk factor for
      incident MetS (OR 1.42, 95% CI 1.04-1.95, for each 10% increase).OSA is
      independently associated with an increased risk of developing MetS through
      mediation of nocturnal hypoxaemia in the general population.

PMID- 30287473
TI  - The Cystic Fibrosis Airway Milieu Enhances Rescue of F508del in a Pre-Clinical
      Model.

PMID- 30287474
TI  - Endoplasmic Reticulum Homeostasis Is Modulated by the Forkhead Transcription
      Factor FKH-9 During Infection of Caenorhabditis elegans.
AB  - Animals have evolved critical mechanisms to maintain cellular and organismal
      proteostasis during development, disease, and exposure to environmental
      stressors. The Unfolded Protein Response (UPR) is a conserved pathway that senses
      and responds to the accumulation of misfolded proteins in the endoplasmic
      reticulum (ER) lumen. We have previously demonstrated that the IRE-1-XBP-1 branch
      of the UPR is required to maintain Caenorhabditis elegans ER homeostasis during
      larval development in the presence of pathogenic Pseudomonas aeruginosa In this
      study, we identify loss-of-function mutations in four conserved transcriptional
      regulators that suppress the larval lethality of xbp-1 mutant animals caused by
      immune activation in response to infection by pathogenic bacteria: FKH-9, a
      forkhead family transcription factor; ARID-1, an ARID/Bright domain-containing
      transcription factor; HCF-1, a transcriptional regulator that associates with
      histone modifying enzymes; and SIN-3, a subunit of a histone deacetylase complex.
      Further characterization of FKH-9 suggests that loss of FKH-9 enhances resistance
      to the ER toxin tunicamycin and results in enhanced ER-associated degradation
      (ERAD). Increased ERAD activity of fkh-9 loss-of-function mutants is accompanied
      by a diminished capacity to degrade cytosolic proteasomal substrates and a
      corresponding increased sensitivity to the proteasomal inhibitor bortezomib. Our
      data underscore how the balance between ER and cytosolic proteostasis can be
      influenced by compensatory activation of ERAD during the physiological ER stress
      of infection and immune activation.

PMID- 30287476
TI  - Association between socioeconomic status and risk of hospitalization due to child
      maltreatment in the USA.
AB  - Child maltreatment remains a significant problem in the USA. There is a dearth of
      literature examining the association of socioeconomic status (SES) and incidence
      of child maltreatment among hospitalized children across the entire USA. Our aim
      was to study the association between SES and incidence and mortality from child
      maltreatment among hospitalized children in the USA. We used 2013-2014 data from
      the Nationwide Inpatient Sample, a discharge database representative of all
      hospitals in the USA. International Classification of Diseases-9 codes for
      general child maltreatment were used to identify patients discharged with a
      primary diagnosis of child maltreatment. Trends in the incidence and outcomes of
      child maltreatment were compared with SES based on quartiles (Qx) of median
      household income. In 2013-2014, there were a total of about 2.3 million pediatric
      discharges. Out of these, a total of 8985 had a primary diagnosis of child
      maltreatment. Approximately 40 per cent of the cases were from families with the
      lowest SES (Q1). In-hospital mortality was 2.4 per cent in Q1 (lowest SES)
      compared with 0.4 per cent in Q4 (highest SES). We conclude that children from
      lower SES households have a higher incidence of child maltreatment and have worse
      outcomes, including significantly higher in-hospital mortality among hospitalized
      children. This trend was generally consistent across all age groups and
      ethnicities. To our knowledge, this is the first report studying the association
      between SES and children with child maltreatment among hospitalized children
      across the entire USA.

PMID- 30287475
TI  - Plasma haptoglobin level can augment NT-proBNP to predict poor outcome in
      patients with severe acute decompensated heart failure.
AB  - To evaluate the use of plasma haptoglobin (Hp) levels and N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) in predicting survival in patients with severe
      acute decompensated heart failure (AHF). Management of AHF is challenging.
      Identifying markers associated with patient prognosis in this disease is
      clinically important. In this prospective observational study, plasma Hp and NT
      proBNP levels were measured. Receiver operating characteristic (ROC) curves were
      used to identify cut-offs of Hp and NT-proBNP with the greatest specificity and
      sensitivity for predicting overall survival and cardiovascular-related survival.
      The cut-off values were tested in patients with AHF (n=41). The cut-off value
      with the greatest specificity and sensitivity with respect to overall survival
      and for cardiovascular-related survival for Hp was 177. 1 ng/mL for both outcomes
      and for NT-proBNP was 34 246.0 pg/mL and 11 848.5 ng/mL, respectively. Using
      these cut-off values, this study found that patients with lower baseline Hp
      levels (<177. 1 ng/mL) or higher baseline NT-proBNP (>=34 246 pg/mL) were more
      likely to have shorter overall survival. Similarly, patients with <177. 1 ng/mL
      of Hp and >=11 848.5 pg/mL of NT-proBNP had the highest risk of death related to
      cardiovascular disease. Our findings indicate that Hp and NT-proBNP using
      specific cut-off values for AHF can be used to determine risk of survival in
      these patients.

PMID- 30287477
TI  - The Phosphate Binder Ferric Citrate Alters the Gut Microbiome in Rats with
      Chronic Kidney Disease.
AB  - In chronic kidney disease (CKD), the gut microbiome is altered and bacterial
      derived uremic toxins promote systemic inflammation and cardiovascular disease.
      Ferric citrate complex is a dietary phosphate binder prescribed for patients with
      end-stage kidney disease to treat hyperphosphatemia and secondary
      hyperparathyroidism. Iron is an essential nutrient in both microbes and mammals.
      This study was undertaken to test the hypothesis that the large iron load
      administered with ferric citrate in CKD may significantly change the gut
      microbiome. Male Sprague-Dawley rats underwent 5/6 nephrectomy to induce CKD.
      Normal control and CKD rats were randomized to regular chow or a 4% ferric
      citrate diet for 6 weeks. Fecal and cecal microbial DNA was analyzed via 16S
      ribosomal RNA gene sequencing on the Illumina MiSeq system. CKD rats had lower
      abundances of Firmicutes and Lactobacillus compared with normal rats and had
      lower overall gut microbial diversity. CKD rats treated with ferric citrate had
      improved hemoglobin and creatinine clearance and amelioration of
      hyperphosphatemia and hypertension. Ferric citrate treatment increased bacterial
      diversity in CKD rats almost to levels observed in control rats. The
      tryptophanase-possessing families Verrucomicrobia, Clostridiaceae, and
      Enterobacteriaceae were increased by ferric citrate treatment. The uremic toxins
      indoxyl sulfate and p-cresyl sulfate were not increased with ferric citrate
      treatment. Verrucomicrobia was largely represented by Akkermansia muciniphila,
      which has important roles in mucin degradation and gut barrier integrity. In
      summary, ferric citrate therapy in CKD rats was associated with significant
      changes in the gut microbiome and beneficial kidney and blood pressure
      parameters.

PMID- 30287481
TI  - Rare variants of the FMN riboswitch class in Clostridium difficile and other
      bacteria exhibit altered ligand specificity.
AB  - Many bacteria use FMN (flavin mononucleotide) riboswitches to control the
      expression of genes responsible for the biosynthesis and transport of this enzyme
      cofactor or its precursor, riboflavin. Rare variants of FMN riboswitches found in
      strains of Clostridium difficile and some other bacteria typically control the
      expression of proteins annotated as transporters, including multidrug efflux
      pumps. These RNAs no longer recognize FMN, and differ from the original
      riboswitch consensus sequence at nucleotide positions normally involved in
      binding of the ribityl and phosphate moieties of the cofactor. Representatives of
      one of the two variant subtypes were found to bind the FMN precursor riboflavin
      and the FMN degradation products lumiflavin and lumichrome. Although the
      biologically relevant ligand sensed by these variant FMN riboswitches remains
      uncertain, our findings suggest that many strains of C. difficile might use rare
      riboswitches to sense flavin degradation products and activate transporters for
      their detoxification.

PMID- 30287482
TI  - Proximal muscle weakness and skin rash.

PMID- 30287480
TI  - SOX4 controls invariant NKT cell differentiation by tuning TCR signaling.
AB  - Natural killer T (NKT) cells expressing the invariant T cell receptor (iTCR)
      serve an essential function in clearance of certain pathogens and have been
      implicated in autoimmune and allergic diseases. Complex effector programs of
      these iNKT cells are wired in the thymus, and upon thymic egress, they can
      respond within hours of antigenic challenges, classifying iNKT cells as innate
      like. It has been assumed that the successful rearrangement of the invariant
      iTCRalpha chain is the central event in the divergence of immature thymocytes to
      the NKT cell lineage, but molecular properties that render the iTCR signaling
      distinct to permit the T cell lineage diversification remain obscure. Here we
      show that the High Mobility Group (HMG) transcription factor (TF) SOX4 controls
      the production of iNKT cells by inducing MicroRNA-181 (Mir181) to enhance TCR
      signaling and Ca2+ fluxes in precursors. These results suggest the existence of
      tailored, permissive gene circuits in iNKT precursors for innate-like T cell
      development.

PMID- 30287478
TI  - SENSITIVE TO SALT1, An Endoplasmic Reticulum-Localized Chaperone, Positively
      Regulates Salt Resistance.
AB  - Salt stress seriously affects plant growth and development. Through genetic
      screening, we identified and characterized an Arabidopsis (Arabidopsis thaliana)
      sensitive to salt1 (ses1) mutant. SES1 was ubiquitously expressed and induced by
      salt treatment. The salt-sensitive phenotype of ses1 was due neither to the
      overaccumulation of Na+ nor to the suppression of salt tolerance-associated
      genes. SES1 encoded an uncharacterized endoplasmic reticulum (ER)-localized
      protein. Coinciding with its subcellular distribution, ses1 exhibited
      overactivation of unfolded protein response genes and was largely influenced by
      severe ER stress. Biochemical evidence revealed that SES1 functions as an
      important molecular chaperone to alleviate salt-induced ER stress. Furthermore,
      the ER stress sensor basic leucine zipper factor17 transactivated SES1 by binding
      directly to its promoter region. These results provide insights into salt stress
      responses and ER homeostasis and shed light on the mechanism by which SES1
      modulates salt resistance.

PMID- 30287483
TI  - US drug wholesaler to pay $625m over allegations it tampered with cancer drugs
      for profit.

PMID- 30287479
TI  - Humanized GPIbalpha-von Willebrand factor interaction in the mouse.
AB  - The interaction of platelet glycoprotein Ibalpha (GPIbalpha) with von Willebrand
      factor (VWF) initiates hemostasis after vascular injury and also contributes to
      pathological thrombosis. GPIbalpha binding to the VWF A1 domain (VWFA1) is a
      target for antithrombotic intervention, but attempts to develop pharmacologic
      inhibitors have been hindered by the lack of animal models because of the species
      specificity of the interaction. To address this problem, we generated a knockin
      mouse with Vwf exon 28-encoding domains A1 and A2 replaced by the human homolog
      (VWFh28). VWFh28 mice (M1HA) were crossbred with a transgenic mouse strain
      expressing human GPIbalpha on platelets (mGPIbalphanull;hGPIbalphaTg; H1MA) to
      generate a new strain (H1HA) with humanized GPIbalpha-VWFA1 binding. Plasma VWF
      levels in the latter 3 strains were similar to those of wild-type mice (M1MA).
      Compared with the strains that had homospecific GPIbalpha-VWF pairing (M1MA and
      H1HA), M1HA mice of those with heterospecific pairing had a markedly greater
      prolongation of tail bleeding time and attenuation of thrombogenesis after injury
      to the carotid artery than H1MA mice. Measurements of GPIbalpha-VWFA1 binding
      affinity by surface plasmon resonance agreed with the extent of observed
      functional defects. Ristocetin-induced platelet aggregation was similar in H1HA
      mouse and human platelet-rich plasma, and it was comparably inhibited by
      monoclonal antibody NMC-4, which is known to block human GPIbalpha-VWFA1 binding,
      which also inhibited FeCl3-induced mouse carotid artery thrombosis. Thus, the
      H1HA mouse strain is a fully humanized model of platelet GPIbalpha-VWFA1 binding
      that provides mechanistic and pharmacologic information relevant to human
      hemostatic and thrombotic disorders.

PMID- 30287484
TI  - Conservative conference: May announces new cancer strategy to boost survival
      rates.

PMID- 30287485
TI  - Integrative genomic analysis of mouse and human hepatocellular carcinoma.
AB  - Cancer genomics has enabled the exhaustive molecular characterization of tumors
      and exposed hepatocellular carcinoma (HCC) as among the most complex cancers.
      This complexity is paralleled by dozens of mouse models that generate
      histologically similar tumors but have not been systematically validated at the
      molecular level. Accurate models of the molecular pathogenesis of HCC are
      essential for biomedical progress; therefore we compared genomic and
      transcriptomic profiles of four separate mouse models [MUP transgenic, TAK1
      knockout, carcinogen-driven diethylnitrosamine (DEN), and Stelic Animal Model
      (STAM)] with those of 987 HCC patients with distinct etiologies. These four
      models differed substantially in their mutational load, mutational signatures,
      affected genes and pathways, and transcriptomes. STAM tumors were most
      molecularly similar to human HCC, with frequent mutations in Ctnnb1, similar
      pathway alterations, and high transcriptomic similarity to high-grade,
      proliferative human tumors with poor prognosis. In contrast, TAK1 tumors better
      reflected the mutational signature of human HCC and were transcriptionally
      similar to low-grade human tumors. DEN tumors were least similar to human disease
      and almost universally carried the Braf V637E mutation, which is rarely found in
      human HCC. Immune analysis revealed that strain-specific MHC-I genotype can
      influence the molecular makeup of murine tumors. Thus, different mouse models of
      HCC recapitulate distinct aspects of HCC biology, and their use should be adapted
      to specific questions based on the molecular features provided here.

PMID- 30287487
TI  - Native-state imaging of calcifying and noncalcifying microalgae reveals
      similarities in their calcium storage organelles.
AB  - Calcium storage organelles are common to all eukaryotic organisms and play a
      pivotal role in calcium signaling and cellular calcium homeostasis. In most
      organelles, the intraorganellar calcium concentrations rarely exceed micromolar
      levels. Acidic organelles called acidocalcisomes, which concentrate calcium into
      dense phases together with polyphosphates, are an exception. These organelles
      have been identified in diverse organisms, but, to date, only in cells that do
      not form calcium biominerals. Recently, a compartment storing molar levels of
      calcium together with phosphorous was discovered in an intracellularly calcifying
      alga, the coccolithophore Emiliania huxleyi, raising a possible connection
      between calcium storage organelles and calcite biomineralization. Here we used
      cryoimaging and cryospectroscopy techniques to investigate the anatomy and
      chemical composition of calcium storage organelles in their native state and at
      nanometer-scale resolution. We show that the dense calcium phase inside the
      calcium storage compartment of the calcifying coccolithophore Pleurochrysis
      carterae and the calcium phase stored in acidocalcisomes of the noncalcifying
      alga Chlamydomonas reinhardtii have common features. Our observations suggest
      that this strategy for concentrating calcium is a widespread trait and has been
      adapted for coccolith formation. The link we describe between acidocalcisomal
      calcium storage and calcium storage in coccolithophores implies that our
      physiological and molecular genetic understanding of acidocalcisomes could have
      relevance to the calcium pathway underlying coccolithophore calcification,
      offering a fresh entry point for mechanistic investigations on the adaptability
      of this process to changing oceanic conditions.

PMID- 30287486
TI  - Cbln2 and Cbln4 are expressed in distinct medial habenula-interpeduncular
      projections and contribute to different behavioral outputs.
AB  - Cerebellins are important neurexin ligands that remain incompletely understood.
      Two critical questions in particular remain unanswered: do different cerebellins
      perform distinct functions, and do these functions act in the initial
      establishment of synapses or in rendering nascent synapses capable of normal
      synaptic transmission? Here we show that in mice, Cbln2 and Cbln4 are expressed
      in the medial habenula (MHb) nucleus in different types of neurons that project
      to distinct target neurons in the interpeduncular nucleus. Conditional genetic
      deletion of Cbln2 in the MHb impaired synaptic transmission at Cbln2+ synapses in
      the interpeduncular neurons within 3 wk, but decreased synapse numbers only after
      3 mo, suggesting a functional, but not a structural, requirement for Cbln2 in
      synapses formed by Cbln2-expressing neurons. In contrast, genetic deletions of
      Cbln4 in the MHb had no major effect on synaptic transmission or synapse numbers
      in interpeduncular target neurons. Nevertheless, MHb ablation of both Cbln2 and
      Cbln4 significantly impaired behavioral responses in mice, but affected different
      types of behaviors. Specifically, Cbln2 MHb deletions decreased spatial learning,
      as measured in the water T-maze, whereas Cbln4 MHb deletions increased anxiety
      levels, as monitored in the open field test and elevated plus maze. Thus, Cbln2
      and Cbln4 are expressed in distinct MHb neurons that contribute to different
      behaviors.

PMID- 30287489
TI  - Evidence for Stabilizing Selection Driving Mutational Turnover of Short Motifs in
      the Eukaryotic Complementary Sex Determiner (Csd) Protein.
AB  - Short linear motifs (SLiMs) can play pivotal functional roles in proteins, such
      as targeting proteins to specific subcellular localizations, modulating the
      efficiency of translation and tagging proteins for degradation. Until recently we
      had little knowledge about SLiM evolution. Only a few amino acids in these motifs
      are functionally important, making them likely to evolve ex nihilo and suggesting
      that they can play key roles in protein evolution. Several reports now suggest
      that these motifs can appear and disappear while their function in the protein is
      preserved, a process sometimes referred to as "turnover". However, there has been
      a lack of specific experiments to determine whether independently evolved motifs
      do indeed have the same function, which would conclusively determine whether the
      process of turnover actually occurs. In this study, we experimentally detected
      evidence for such a mutational turnover process for nuclear localization signals
      (NLS) during the post-duplication divergence of the Complementary sex determiner
      (Csd) and Feminizer (Fem) proteins in the honeybee (Apis mellifera) lineage.
      Experiments on the nuclear transport activity of protein segments and those of
      the most recent common ancestor (MRCA) sequences revealed that three new NLS
      motifs evolved in the Csd protein during the post-duplication divergence while
      other NLS motifs were lost that existed before duplication. A screen for
      essential and newly evolved amino acids revealed that new motifs in the Csd
      protein evolved by one or two missense mutations coding for lysine. Amino acids
      that were predating the duplication were also essential in the acquisition of the
      C1 motif suggesting that the ex nihilo origin was constrained by preexisting
      amino acids in the physical proximity. Our data support a model in which
      stabilizing selection maintains the constancy of nuclear transport function but
      allowed mutational turnover of the encoding NLS motifs.

PMID- 30287490
TI  - Multiphasic effect of vinyl pyrrolidone polymers on amyloidogenesis, from
      macromolecular crowding to inhibition.
AB  - Deposition of misfolded amyloid polypeptides, associated with cell death, is the
      hallmark of many degenerative diseases (e.g. type II diabetes mellitus and
      Alzheimer's disease). In vivo, cellular and extracellular spaces are occupied by
      a high volume fraction of macromolecules. The resulting macromolecular crowding
      energetically affects reactions. Amyloidogenesis can either be promoted by
      macromolecular crowding through the excluded volume effect or inhibited due to a
      viscosity increase reducing kinetics. Macromolecular crowding can be mimicked in
      vitro by the addition of non-specific polymers, e.g. Ficoll, dextran and
      polyvinyl pyrrolidone (PVP), the latter being rarely used to study amyloid
      systems. We investigated the effect of PVP on amyloidogenesis of full-length
      human islet amyloid polypeptide (involved in type II diabetes) using
      fibrillisation and surface activity assays, ELISA, immunoblot and microscale
      thermophoresis. We demonstrate that high molecular mass PVP360 promotes
      amyloidogenesis due to volume exclusion and increase in effective amyloidogenic
      monomer concentration, like other crowders, but without the confounding effects
      of viscosity and surface activity. Interestingly, we also show that low molecular
      mass PVP10 has unique inhibitory properties as inhibition of fibril elongation
      occurs mainly in the bulk solution and is due to PVP10 directly and strongly
      interacting with amyloid species rather than the increase in viscosity typically
      associated with macromolecular crowding. In vivo, amyloidogenesis might be
      affected by the properties and proximity of endogenous macromolecular crowders,
      which could contribute to changes in associated pathogenesis. More generally, the
      PVP10 molecular backbone could be used to design small compounds as potential
      inhibitors of toxic species formation.

PMID- 30287488
TI  - Noncanonical autophagy at ER exit sites regulates procollagen turnover.
AB  - Type I collagen is the main component of bone matrix and other connective
      tissues. Rerouting of its procollagen precursor to a degradative pathway is
      crucial for osteoblast survival in pathologies involving excessive intracellular
      buildup of procollagen that is improperly folded and/or trafficked. What cellular
      mechanisms underlie this rerouting remains unclear. To study these mechanisms, we
      employed live-cell imaging and correlative light and electron microscopy (CLEM)
      to examine procollagen trafficking both in wild-type mouse osteoblasts and
      osteoblasts expressing a bone pathology-causing mutant procollagen. We found that
      although most procollagen molecules successfully trafficked through the secretory
      pathway in these cells, a subpopulation did not. The latter molecules appeared in
      numerous dispersed puncta colocalizing with COPII subunits, autophagy markers and
      ubiquitin machinery, with more puncta seen in mutant procollagen-expressing
      cells. Blocking endoplasmic reticulum exit site (ERES) formation suppressed the
      number of these puncta, suggesting they formed after procollagen entry into
      ERESs. The punctate structures containing procollagen, COPII, and autophagic
      markers did not move toward the Golgi but instead were relatively immobile. They
      appeared to be quickly engulfed by nearby lysosomes through a bafilomycin
      insensitive pathway. CLEM and fluorescence recovery after photobleaching
      experiments suggested engulfment occurred through a noncanonical form of
      autophagy resembling microautophagy of ERESs. Overall, our findings reveal that a
      subset of procollagen molecules is directed toward lysosomal degradation through
      an autophagic pathway originating at ERESs, providing a mechanism to remove
      excess procollagen from cells.

PMID- 30287491
TI  - Variants with increased negative electrostatic potential in the Cx50 gap junction
      pore increased unitary channel conductance and magnesium modulation.
AB  - Gap junction (GJ) channels are oligomers of connexins forming channels linking
      neighboring cells. GJs formed by different connexins show distinct unitary
      channel conductance (gammaj), transjunctional voltage-dependent gating (V j
      gating) properties, and modulation by intracellular magnesium ([Mg2+]i). The
      underlying molecular determinants are not fully clear. Previous experimental
      evidence indicates that residues in the amino terminal (NT) and initial segment
      of the first extracellular (E1) domain influence the gammaj, V j-gating, and/or
      [Mg2+]i modulation in several GJs. Increasing negatively charged residues in Cx50
      (connexin50) E1 (G46D or G46E) increased gammaj, while increasing positively
      charged residue (G46K) reduced the gammaj Sequence alignment of Cx50 and Cx37 in
      the NT and E1 domains revealed that in Cx50 G8 and V53, positions are negatively
      charged residues in Cx37 (E8 and E53, respectively). To evaluate these residues
      together, we generated a triple variant in Cx50, G8E, G46E, and V53E
      simultaneously to study its gammaj, V j-gating properties, and modulation by
      [Mg2+]i Our data indicate that the triple variant and individual variants G8E,
      G46E, and V53E significantly increased Cx50 GJ gammaj without a significant
      change in the V j gating. In addition, elevated [Mg2+]i reduced gammaj in Cx50
      and all the variant GJs. These results and our homology structural models suggest
      that these NT/E1 residues are likely to be pore-lining and the variants increased
      the negative electrostatic potentials along the GJ pore to facilitate the gammaj
      of this cation-preferring GJ channel. Our results indicate that electrostatic
      properties of the Cx50 GJ pore are important for the gammaj and the [Mg2+]i
      modulation.

PMID- 30287492
TI  - Structure-function studies of the asparaginyl-tRNA synthetase from Fasciola
      gigantica: understanding the role of catalytic and non-catalytic domains.
AB  - The asparaginyl-tRNA synthetase (NRS) catalyzes the attachment of asparagine to
      its cognate tRNA during translation. NRS first catalyzes the binding of Asn and
      ATP to form the NRS-asparaginyl adenylate complex, followed by the esterification
      of Asn to its tRNA. We investigated the role of constituent domains in regulating
      the structure and activity of Fasciola gigantica NRS (FgNRS). We cloned the full
      length FgNRS, along with its various truncated forms, expressed, and purified the
      corresponding proteins. Size exclusion chromatography indicated a role of the
      anticodon-binding domain (ABD) of FgNRS in protein dimerization. The N-terminal
      domain (NTD) was not essential for cognate tRNA binding, and the hinge region
      between the ABD and the C-terminal domain (CTD) was crucial for regulating the
      enzymatic activity. Molecular docking and fluorescence quenching experiments
      elucidated the binding affinities of the substrates to various domains. The
      molecular dynamics simulation of the modeled protein showed the presence of an
      unstructured region between the NTD and ABD that exhibited a large number of
      conformations over time, and further analysis indicated this region to be
      intrinsically disordered. The present study provides information on the
      structural and functional regulation, protein-substrate(s) interactions and
      dynamics, and the role of non-catalytic domains in regulating the activity of
      FgNRS.

PMID- 30287493
TI  - A new era for treatment of drug-resistant tuberculosis.

PMID- 30287494
TI  - Risk factors for lung disease progression in children with cystic fibrosis.

PMID- 30287495
TI  - Breaking news: DNA damage and repair pathways in COPD and implications for
      pathogenesis and treatment.

PMID- 30287496
TI  - "Safety of nintedanib added to pirfenidone treatment for idiopathic pulmonary
      fibrosis." Kevin R. Flaherty, Charlene D. Fell, J. Terrill Huggins, Hilario
      Nunes, Robert Sussman, Claudia Valenzuela, Ute Petzinger, John L. Stauffer, Frank
      Gilberg, Monica Bengus and Marlies Wijsenbeek. Eur Respir J 2018; 52: 1800230.

PMID- 30287497
TI  - Men outnumber women three to one in some specialties.

PMID- 30287498
TI  - A negative feedback loop between long noncoding RNA NBAT1 and Sox9 inhibits the
      malignant progression of gastric cancer cells.
AB  - Long noncoding RNAs (lncRNAs) play critical roles in carcinogenesis and
      progression, and act as important gene expression modulators. Recent evidence
      indicates that lncRNA neuroblastoma associated transcript 1 (NBAT1) functions as
      a tumor suppressor in some types of human cancers. However, its functional role
      in the development of gastric cancer (GC) remains unknown. The aim of this
      research was to investigate the clinical significance and biological functions of
      NBAT1 in GC. NBAT1 was found to be significantly down-regulated in GC tissue.
      Decreased NBAT1 expression was correlated with poor differentiation, higher tumor
      stage and lymph node metastasis, and poor prognosis. Functional assays showed
      that NBAT1 inhibited GC proliferation, migration, and invasion. NBAT1 also
      suppressed proliferation, migration, and capillary tube formation of human
      umbilical vein endothelial cells (HUVECs). Mechanistically, NBAT1 interacted with
      Sox9, and reduced its protein stability by promoting it from polyubiquitination
      and proteasome-dependent degradation. Moreover, we revealed that Sox9 could
      occupy the NBAT1 promoter to inactivate its transcription. The negative feedback
      loop of NBAT1 and Sox9 continuously enhanced the suppressive effects. In
      conclusion, these findings suggest that feedback regulation of NBAT1 and Sox9
      served as a critical effector in GC progression.

PMID- 30287499
TI  - Effect of microRNA-495 on lower extremity deep vein thrombosis through the TLR4
      signaling pathway by regulation of IL1R1.
AB  - Lower extremity deep vein thrombosis (LEDVT) a common peripheral vascular
      disease, caused by a blood clot in a deep vein is usually accompanied by swelling
      of the lower limbs. MicroRNAs (miRs) have been reported to play roles in LEDVT.
      We investigated the effect of miR-495 on LEDVT via TLR4 signaling pathway through
      IL1R1. LEDVT mouse model was established, and the femoral vein (FV) tissues were
      collected to detect expressions of miR-495, IL1R1, and TLR4 signaling-related
      genes. The expressions of both CD31 and CD34 (markers for endothelial progenitor
      cells) in the FV endothelial cells as well as the proportion of CD31+/CD34+ cells
      in peripheral blood were measured in order to evaluate thrombosis. The effect of
      miR-495 on cell viability, cell cycle, and apoptosis was analyzed. IL1R1 was
      confirmed as the target gene of miR-495. Besides, inhibiting the miR-495
      expression could increase IL1R1 expression along with activating the TLR4
      signaling pathway. The total number of the leukocytes along with the ratio of
      weight to length of thrombus in the FV tissue showed an increase. The
      overexpression of miR-495 could promote FV endothelial cell viability. By
      injecting agomiR-495 and antagomiR-495 in vivo, the number of leukocytes in the
      FV tissues and the ratio of weight to length of thrombus were significantly
      decreased in the mice injected with the overexpressed miR-495, and the IL1R1/TLR4
      signaling pathway was inhibited. Collectively, overexpressed miR-495 directly
      promotes proliferation while simultaneously inhibiting apoptosis of FV
      endothelial cells, alleviating FV thrombosis by inhibiting IL1R1 via suppression
      of TLR4 signaling pathway.

PMID- 30287500
TI  - Comment on Tauriainen et al.: Serum, liver and bile sitosterol and sitostanol in
      obese patients with and without NAFLD.
AB  - This short article provides a comment on the recent article by Tauriainen et al.
      [Bioscience Reports (2018) 38, BSR20171274 https://doi.org/10.1042/BSR20171274].

PMID- 30287501
TI  - Fangjing decoction relieves febrile seizures-induced hippocampal neuron apoptosis
      in rats via regulating the Akt/mTOR pathway.
AB  - Background: Fangjing decoction is a Traditional Chinese Medicine that exhibits
      anticonvulsive effects in treating febrile seizures (FS). Its action mechanism
      and the regulation on Akt/mammalian target of rapamycin (mTOR) pathway were
      revealed in the present study.Methods: FS model was established in Sprague-Dawley
      rats with or without Fangjing decoction treatment. On day 5, following initiation
      of drug treatment, seizures were monitored. Hippocampal neuron apoptosis was
      assessed using terminal dUTP nick end-labeling method. The levels of Bax, protein
      kinase B (Akt), phospho-Akt (p-Akt), mTOR, and p-mTOR proteins were analyzed
      using Western blotting. The content of hippocampal gamma-aminobutyric acid (GABA)
      was measured by using ELISA assay.Results: Compared with the control group (n=8),
      Fangjing decoction effectively shortened escape latency and duration of FS and
      decreased the frequency of FS in rats (n=8). Concomitantly, the apoptosis of
      hippocampal neurons, as well as Bax protein levels were also decreased in FS rats
      which were treated with Fangjing decoction. In addition, the Akt/mTOR signaling
      was found to be activated in rat hippocampus following FS, as evidenced by
      increased p-Akt and p-mTOR, while Fangjing decoction could inhibit the activation
      of Akt/mTOR signaling. Furthermore, the low GABA content in rat hippocampus
      following FS was significantly elevated by Fangjing decoction treatment. More
      importantly, SC79, a specific activator for Akt, apparently attenuated the
      protective effects of Fangjing decoction on FS rats.Conclusion: These results
      suggest that Fangjing decoction protects the hippocampal neurons from apoptosis
      by inactivating Akt/mTOR pathway, which may contribute to mitigating FS-induced
      brain injury.

PMID- 30287502
TI  - Metabolomic profiling of ovary in mice treated with FSH using ultra performance
      liquid chromatography/mass spectrometry.
AB  - The growth and development of follicles are a very complex physiological process
      that is regulated by endocrine, autocrine and paracrine mechanisms. The effect of
      small molecules in follicular microenvironment on follicular growth and
      development has not been clearly analyzed. In the present study, the metabolic
      changes in ovaries of FSH-stimulated mice were investigated. Metabolomic
      profiling of ovary stimulated by FSH were analyzed by ultra-performance liquid
      chromatography/mass spectrometry and characterized by principal components
      analysis and orthogonal partial least squares discriminant analysis. Multivariate
      statistical analysis identified 21 differentially metabolites in positive ion
      mode and 12 in negative ion mode in the FSH-treated mice compared with the
      control mice. These results indicated that various types of phosphatidylcholine
      were changed. Furthermore, the levels of L-Glutamyl 5-phosphate, N-Acetyl-L
      aspartic acid, 4-fumarylacetoacetic acid, adenylylselenate and 5'
      Methylthioadenosine in the ovaries of the FSH-stimulated mice were decreased.
      However, the levels of 19-hydroxytestosterone and 5,10-methenyltetrahydrofolic
      acid were significantly increased in the positive ion mode and negative ion mode,
      respectively. Thirty-three differential metabolites including fatty acid
      metabolism, amino acid metabolism and lipid metabolism in the ovaries of mice
      were affected by FSH injection. The findings of our study provide a new insight
      into understanding the follicular development.

PMID- 30287503
TI  - Zhenbao Pill reduces Treg cell proportion in acute spinal cord injury rats by
      regulating TUG1/miR-214/HSP27 axis.
AB  - Background: Acute spinal cord injury (SCI) is one of the weakest pathologies that
      seriously affect the quality of life of patients. Objective: To study the
      mechanism of how Zhenbao Pill reduces Treg cell proportion and improves acute
      SCI. Methods: A rat SCI model was established. Flow cytometry analysis was
      performed to determine the Treg cell proportion. RNA immunoprecipitation (RIP)
      and RNA pull-down were applied in confirming taurine up-regulated gene 1 (TUG1)
      and miR-214 binding. Intrathecal injection of TUG1 siRNA was also conducted to
      determine the effect of TUG1 in vivo Results: Zhenbao Pill promoted the
      expression of TUG1 and heat shock protein 27 (HSP27) protein, and reduced the
      expression of miR-214 and forkhead box protein p3 (Foxp3) as well as Treg cell
      proportion in a concentration-dependent manner in SCI rats or in vitro cultured
      CD4+ T cells. Knockdown of TUG1 reversed the high protein expression of HSP27 and
      the inhibition of Treg cell proportion as well as Foxp3 protein induced by
      Zhenbao Pill, and miR-214 inhibitor canceled the TUG1 knockdown effect. Further,
      miR-214 mimic reversed the inhibition of Treg cell proportion and Foxp3 protein
      expression by Zhenbao Pill, which was abolished by the overexpression of HSP27.
      The mechanism was validated in animal experiments. Conclusion: Zhenbao Pill
      regulated TUG1/miR-214/HSP27 signaling pathway to reduce Treg cell proportion and
      thus relieve acute SCI.

PMID- 30287504
TI  - lncRNA Gm15290 promotes cell proliferation and invasion in lung cancer through
      directly interacting with and suppressing the tumor suppressor miR-615-5p.
AB  - Long non-coding RNAs (lncRNAs) have been involved in occurrence and progression
      of multiple cancers. In the present study, we investigated the role of lncRNA
      Gm15290 in the proliferation and invasion of non-small cell lung cancer (NSCLC)
      cells. First, we found that lncRNA Gm15290 was markedly up-regulated in tumor
      tissues from NSCLC patients and NSCLC cell lines, compared with adjacent normal
      tissues and normal lung cell line HBE respectively. Then, different
      concentrations of pcDNA-Gm15290 expression vector and Gm15290 siRNA were
      respectively transfected into A549 NSCLC cells. Our results showed that
      overexpression of Gm15290 significantly increased the proliferation and invasion
      of A549 cells and suppressed cell apoptosis. Knockdown of Gm15290 suppressed A549
      cell proliferation and invasion and promoted cell apoptosis. Subsequently, we
      explored the underlying mechanism through which Gm15290 promoted cell
      proliferation and invasion. The output of RNA hybrid bioinformatic tool revealed
      that Gm15290 potentially interacted with tumor suppressor miR-615-5p which
      displayed an opposite expression pattern in the cell lines and a strong negative
      correlation with the levels of Gm15290 in NSCLC patients (r2 = 0.9677, P<0.0001).
      The results of RNA pull-down assays confirmed that Gm15290 directly bound with
      miR-615-5p Gm15290 negatively regulated the expression of miR-615-5p and
      increased the protein levels of miR-615-5p target genes, including IGF2, AKT2,
      and SHMT2 Moreover, miR-615-5p mimic could antagonize the promoting effect of
      Gm15290 on cell proliferation and invasion.

PMID- 30287507
TI  - Indian government dissolves Medical Council of India.

PMID- 30287505
TI  - Proteasome subunit-alpha type-6 protein is post-transcriptionally repressed by
      the microRNA-4490 in diabetic nephropathy.
AB  - A common complication of both type I and type II diabetes is nephropathy,
      characterized by accumulation of extracellular matrix in the glomerular
      mesangium. This indicates a central role of mesangial cells in the
      pathophysiology of diabetic nephropathy. Using the proteomic approach, it was
      earlier elucidated in a rat model that the proteasome subunit-alpha type-6
      protein (PSMA6) is suppressed in the renal cortex in nephropathic kidney.
      However, the underlying mechanism effecting suppression of PSMA6 protein in the
      renal cortex is not yet known. Twenty diabetic patients were enrolled and the
      expression level of PSMA6 in them was detected by immunohistochemistry. The
      protein and mRNA expression levels of PSMA6 in NRK-52E cells under high glucose
      condition were determined by Western blot and quantitative real-time PCR,
      respectively. Dual luciferase assay was used to detect the relationship of PSMA6
      and miR-4490. Our results show that PSMA6 protein is down-regulated in patients
      with diabetic nephropathy compared with healthy control. Using the NRK-52E cell
      line cultured under high glucose condition as an in vitro model of diabetic
      nephropathy, we show that loss of PSMA6 protein expression occured independent of
      changes the in PSMA6 mRNA expression. We next elucidate that PSMA6 mRNA is post
      transcriptionally regulated by the microRNA (miRNA)-4490, whose expression is
      inversely correlated to PSMA6 protein expression. Using reporter assays we show
      that PSMA6 is a direct target of the miR-4490. Exogenous manipulation of miR-4490
      levels modulated expression of PSMA6, indicating that miR-4490 can be tested as a
      biomarker for nephropathy in diabetic patients.

PMID- 30287506
TI  - Biochemical significance of limonene and its metabolites: future prospects for
      designing and developing highly potent anticancer drugs.
AB  - Monocyclic monoterpenes have been recognized as useful pharmacological
      ingredients due to their ability to treat numerous diseases. Limonene and
      perillyl alcohol as well as their metabolites (especially perillic acid and its
      methyl ester) possess bioactivities such as antitumor, antiviral, anti
      inflammatory, and antibacterial agents. These therapeutic properties have been
      well documented. Based on the aforementioned biological properties of limonene
      and its metabolites, their structural modification and development into effective
      drugs could be rewarding. However, utilization of these monocyclic monoterpenes
      as scaffolds for the design and developments of more effective chemoprotective
      agents has not received the needed attention by medicinal scientists. Recently,
      some derivatives of limonene metabolites have been synthesized. Nonetheless,
      there have been no thorough studies on their pharmacokinetic and pharmacodynamic
      properties as well as their inhibition against isoprenylation enzymes. In this
      review, recent research progress in the biochemical significance of limonene and
      its metabolites was summarized with emphasis on their antitumor effects. Future
      prospects of these bioactive monoterpenes for drug design and development are
      also highlighted.

PMID- 30287509
TI  - Mitochondrial diseases caused by dysfunctional mitochondrial protein import.
AB  - Mitochondria are essential organelles which perform complex and varied functions
      within eukaryotic cells. Maintenance of mitochondrial health and functionality is
      thus a key cellular priority and relies on the organelle's extensive proteome.
      The mitochondrial proteome is largely encoded by nuclear genes, and mitochondrial
      proteins must be sorted to the correct mitochondrial sub-compartment post
      translationally. This essential process is carried out by multimeric and dynamic
      translocation and sorting machineries, which can be found in all four
      mitochondrial compartments. Interestingly, advances in the diagnosis of genetic
      disease have revealed that mutations in various components of the human import
      machinery can cause mitochondrial disease, a heterogenous and often severe
      collection of disorders associated with energy generation defects and a
      multisystem presentation often affecting the cardiovascular and nervous systems.
      Here, we review our current understanding of mitochondrial protein import systems
      in human cells and the molecular basis of mitochondrial diseases caused by
      defects in these pathways.

PMID- 30287510
TI  - Post-translational modification of nucleoid-associated proteins: an extra layer
      of functional modulation in bacteria?
AB  - Post-translational modification (PTM) of histones has been investigated in
      eukaryotes for years, revealing its widespread occurrence and functional
      importance. Many PTMs affect chromatin folding and gene activity. Only recently
      the occurrence of such modifications has been recognized in bacteria. However, it
      is unclear whether PTM of the bacterial counterparts of eukaryotic histones,
      nucleoid-associated proteins (NAPs), bears a comparable significance. Here, we
      scrutinize proteome mass spectrometry data for PTMs of the four most abundantly
      present NAPs in Escherichia coli (H-NS, HU, IHF and FIS). This approach allowed
      us to identify a total of 101 unique PTMs in the 11 independent proteomic studies
      covered in this review. Combined with structural and genetic information on these
      proteins, we describe potential effects of these modifications (perturbed DNA
      binding, structural integrity or interaction with other proteins) on their
      function.

PMID- 30287508
TI  - RAS variant signalling.
AB  - RAS proteins are small GTPases that regulate signalling networks that control
      cellular proliferation and survival. They are frequently mutated in cancer and a
      commonly occurring group of developmental disorders called RASopathies. We
      discuss recent findings describing how RAS isoforms and different activating
      mutations differentially contribute to normal and disease-associated biology and
      the mechanisms that have been proposed to underpin this.

PMID- 30287512
TI  - Philip Hieter: 2018 George W. Beadle Award.
AB  - The Genetics Society of America's (GSA) George W. Beadle Award honors individuals
      who have made outstanding contributions to the community of genetics researchers
      and who exemplify the qualities of its namesake. For his work fostering
      communication and collaboration among members of the many subfields of genetics,
      Philip Hieter of the University of British Columbia has been named 2018's
      recipient of the award. Among his contributions are many initiatives that aim to
      better link human and model organism geneticists, including the Canadian Rare
      Diseases Models and Mechanisms Network-a consortium that connects investigators
      who identify rare disease genes in humans to basic scientists who can study the
      genes in model organisms.

PMID- 30287511
TI  - Carcinogens and DNA damage.
AB  - Humans are variously and continuously exposed to a wide range of different DNA
      damaging agents, some of which are classed as carcinogens. DNA damage can arise
      from exposure to exogenous agents, but damage from endogenous processes is
      probably far more prevalent. That said, epidemiological studies of migrant
      populations from regions of low cancer risk to high cancer risk countries point
      to a role for environmental and/or lifestyle factors playing a pivotal part in
      cancer aetiology. One might reasonably surmise from this that carcinogens found
      in our environment or diet are culpable. Exposure to carcinogens is associated
      with various forms of DNA damage such as single-stand breaks, double-strand
      breaks, covalently bound chemical DNA adducts, oxidative-induced lesions and DNA
      DNA or DNA-protein cross-links. This review predominantly concentrates on DNA
      damage induced by the following carcinogens: polycyclic aromatic hydrocarbons,
      heterocyclic aromatic amines, mycotoxins, ultraviolet light, ionising radiation,
      aristolochic acid, nitrosamines and particulate matter. Additionally, we allude
      to some of the cancer types where there is molecular epidemiological evidence
      that these agents are aetiological risk factors. The complex role that
      carcinogens play in the pathophysiology of cancer development remains obscure,
      but DNA damage remains pivotal to this process.

PMID- 30287513
TI  - How Mendel's Interest in Inheritance Grew out of Plant Improvement.
AB  - Despite the fact that Gregor Mendel is generally respected as the founder of
      genetics, little is known about the origin of and motivation for his
      revolutionary work. No primary sources are known that discuss his work during the
      period of his pea crossing experiments. Here, we report on two previously unknown
      interconnected local newspaper articles about Mendel's work that predate his
      famous Pisum lectures by 4 years. These articles describe Mendel as a plant
      breeder and a horticulturist. We argue that Mendel's initial interests concerned
      crop improvement, but that with time he became more interested in fundamental
      questions about inheritance, fertilization, and natural hybridization.

PMID- 30287517
TI  - Doctor who changed patient consent form to cover up mistake is struck off.

PMID- 30287519
TI  - Omega-3 polyunsaturated fatty acids reduce preterm labor by inhibiting
      trophoblast cathepsin S and inflammasome activation.
AB  - Preterm labor is associated with inflammation and infection. The mechanisms
      underlying the role of omega-3 fatty acid in inflammasome activation and
      prevention of preterm labor remain unknown. We hypothesized that omega-3 fatty
      acid can reduce the rate of preterm birth induced by infection and trophoblast
      inflammation. In the present study, we found that inflammasome-related molecules
      and IL-1beta in trophoblasts were activated by TNF-alpha derived from
      lipopolysaccharide (LPS)-stimulated THP-1 cell-conditioned medium (CM) and
      recombinant TNF-alpha protein. The results demonstrated that stimulation with TNF
      alpha caused lysosomal rupture in trophoblasts, which accelerated cathepsin S
      (CTSS) diffusion from lysosomes to the cytosol and activated NLRP1 (nacht domain
      leucine-rich repeat, and pyd-containing protein 1) and absent in melanoma 2
      (AIM2) inflammasomes, thereby increasing IL-1beta secretion. Moreover, in
      response to LPS challenge, TNF-alpha increased trophoblast cell death and
      decreased cell viability through inflammasome and CTSS activation. Stearidonic
      acid (SDA; 18:4n-3) and docosahexaenoic acid (DHA; 22:6n-3) inhibited
      inflammasome-related molecule synthesis and CTSS and caspase-1 activation, which
      further reduced the preterm delivery rate of pregnant mice induced by LPS (92.9
      compared with 69.7% (DHA); 92.9 compared with 53.5% (SDA)). Higher expression of
      TNF-alpha, IL-1beta, prostaglandin E2, and CTSS, but lower resolvin D1
      expression, was observed in preterm pregnant mice than in controls. Similarly,
      resolvin D1 was highly expressed in women with term delivery compared with women
      with preterm delivery. Thus, SDA and DHA may attenuate macrophage-derived TNF
      alpha inducing CTSS and inflammasome activation, IL-1beta secretion, and
      placental trophoblast cell death. These functions are implicated in the
      preventive effects of SDA and DHA on preterm labor.

PMID- 30287518
TI  - Association of Soluble TNFR-1 Concentrations with Long-Term Decline in Kidney
      Function: The Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: TNF receptor-1 (TNFR-1), which plays a causative role in endothelial
      cell dysfunction and inflammation, is expressed on the cell surface in glomerular
      and peritubular capillary endothelium of the kidneys. Higher soluble TNF receptor
      1 (sTNFR-1) concentrations are associated with kidney disease progression among
      persons with established diabetic kidney disease. However, no studies have
      assessed sTNFR-1's role in long-term kidney function changes in a multiethnic
      population without cardiovascular disease at baseline. METHODS: We tested
      associations between baseline sTNFR-1 concentrations and 10-year decline in eGFR
      (incident >=40% decline and annual proportional decline) among 2548 participants
      in the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study.
      Serum creatinine concentrations were determined at enrollment and study years 3,
      5, and 10. RESULTS: Mean age of participants was 61 years old, 53% were women,
      and mean baseline eGFR was 79 ml/min per 1.73 m2. Serum sTNFR-1 was inversely
      associated with baseline eGFR. Over median follow-up of 9.3 years, 110
      participants developed >=40% decline in eGFR; each SD higher concentration of
      sTNFR1 was associated with higher risk of 40% eGFR decline (adjusted hazard
      ratio, 1.43; 95% confidence interval [95% CI], 1.16 to 1.77; P<0.001). The
      highest sTNFR-1 tertile was associated with adjusted annualized decline in eGFR
      of 1.94% (95% CI, 1.79 to 2.09). Associations persisted across subgroups defined
      by demographics, hypertension, diabetes, and baseline CKD status. CONCLUSIONS:
      Elevated serum sTNFR-1 concentrations are associated with faster declines in eGFR
      over the course of a decade in a multiethnic population, independent of
      previously known risk factors for kidney disease progression.

PMID- 30287520
TI  - Early isolated V-lesion may not truly represent rejection of the kidney
      allograft.
AB  - Intimal arteritis is known to be a negative prognostic factor for kidney
      allograft survival. Isolated v-lesion (IV) is defined as intimal arteritis with
      minimal tubulointerstitial inflammation (TI). Although the Banff classification
      assesses IV as T cell-mediated rejection (TCMR), clinical, and prognostic
      significance of early IV (early IV, eIV) with negative C4d and donor-specific
      antibodies (DSA) remains unclear. To help resolve if such eIV truly represents
      acute rejection, a molecular study was performed. The transcriptome of eIV (n=6),
      T cell-mediated vascular rejection with rich TI (T cell-mediated vascular
      rejection, TCMRV, n=4) and non-rejection histologic findings (n=8) was compared
      using microarrays. A total of 310 genes were identified to be deregulated in
      TCMRV compared with eIV. Gene enrichment analysis categorized deregulated genes
      to be associated primarily with T-cells associated biological processes involved
      in an innate and adaptive immune and inflammatory response. Comparison of
      deregulated gene lists between the study groups and controls showed only a 1.7%
      gene overlap. Unsupervised hierarchical cluster analysis revealed clear
      distinction of eIV from TCMRV and showed similarity with a control group. Up
      regulation of immune response genes in TCMRV was validated using RT-qPCR in a
      different set of eIV (n=12) and TCMRV (n=8) samples. The transcriptome of early
      IV (< 1 month) with negative C4d and DSA is associated with a weak immune
      signature compared with TCMRV and shows similarity with normal findings. Such eIV
      may feature non-rejection origin and reflect an injury distinct from an
      alloimmune response. The present study supports use of molecular methods when
      interpreting kidney allograft biopsy findings.

PMID- 30287521
TI  - Raised intracranial pressure in those presenting with headache.

PMID- 30287522
TI  - Evidence for Chemopreventive and Resilience Activity of Licorice: Glycyrrhiza
      Glabra and G. Inflata Extracts Modulate Estrogen Metabolism in ACI Rats.
AB  - Women are increasingly using botanical dietary supplements (BDS) to reduce
      menopausal hot flashes. Although licorice (Glycyrrhiza sp.) is one of the
      frequently used ingredients in BDS, the exact plant species is often not
      identified. We previously showed that in breast epithelial cells (MCF-10A),
      Glycyrrhiza glabra (GG) and G. inflata (GI), and their compounds differentially
      modulated P450 1A1 and P450 1B1 gene expression, which are responsible for
      estrogen detoxification and genotoxicity, respectively. GG and isoliquiritigenin
      (LigC) increased CYP1A1, whereas GI and its marker compound, licochalcone A
      (LicA), decreased CYP1A1 and CYP1B1 The objective of this study was to determine
      the distribution of the bioactive licorice compounds, the metabolism of LicA, and
      whether GG, GI, and/or pure LicA modulate NAD(P)H quinone oxidoreductase (NQO1)
      in an ACI rat model. In addition, the effect of licorice extracts and compounds
      on biomarkers of estrogen chemoprevention (CYP1A1) as well as carcinogenesis
      (CYP1B1) was studied. LicA was extensively glucuronidated and formed GSH adducts;
      however, free LicA as well as LigC were bioavailable in target tissues after oral
      intake of licorice extracts. GG, GI, and LicA caused induction of NQO1 activity
      in the liver. In mammary tissue, GI increased CYP1A1 and decreased CYP1B1,
      whereas GG only increased CYP1A1 LigC may have contributed to the upregulation of
      CYP1A1 after GG and GI administration. In contrast, LicA was responsible for GI
      mediated downregulation of CYP1B1 These studies highlight the polypharmacologic
      nature of botanicals and the importance of standardization of licorice BDS to
      specific Glycyrrhiza species and to multiple constituents. Cancer Prev Res;
      11(12); 1-12. (c)2018 AACR.

PMID- 30287523
TI  - The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory
      CLL/SLL.
AB  - Duvelisib (also known as IPI-145) is an oral, dual inhibitor of
      phosphatidylinositol 3-kinase delta and gamma (PI3K-delta,gamma) being developed
      for treatment of hematologic malignancies. PI3K-delta,gamma signaling can promote
      B-cell proliferation and survival in clonal B-cell malignancies, such as chronic
      lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). In a phase 1 study,
      duvelisib showed clinically meaningful activity and acceptable safety in CLL/SLL
      patients. We report here the results of DUO, a global phase 3 randomized study of
      duvelisib vs ofatumumab monotherapy for patients with relapsed or refractory (RR)
      CLL/SLL. Patients were randomized 1:1 to oral duvelisib 25 mg twice daily (n =
      160) or ofatumumab IV (n = 159). The study met the primary study end point by
      significantly improving progression-free survival per independent review
      committee assessment compared with ofatumumab for all patients (median, 13.3
      months vs 9.9 months; hazard ratio [HR] = 0.52; P < .0001), including those with
      high-risk chromosome 17p13.1 deletions [del(17p)] and/or TP53 mutations (HR =
      0.40; P = .0002). The overall response rate was significantly higher with
      duvelisib (74% vs 45%; P < .0001) regardless of del(17p) status. The most common
      adverse events were diarrhea, neutropenia, pyrexia, nausea, anemia, and cough on
      the duvelisib arm, and neutropenia and infusion reactions on the ofatumumab arm.
      The DUO trial data support duvelisib as a potentially effective treatment option
      for patients with RR CLL/SLL. This trial was registered at www.clinicaltrials.gov
      as #NCT02004522.

PMID- 30287525
TI  - Helping Babies Breathe-Beyond Training.

PMID- 30287524
TI  - Nuclear Phospholipase C isoenzyme imbalance leads to pathologies in brain,
      hematologic, neuromuscular and fertility disorders.
AB  - Phosphoinositide-specific PLC (PI-PLCs) are involved in signaling pathways
      related to critical cellular functions, such as cell cycle regulation, cell
      differentiation, and gene expression. PI-PLCs are highly expressed in different
      brain areas, and nuclear PI-PLCs have been studied as key enzymes, molecular
      targets, and clinical prognostic/diagnostic factors in many physiopathologic
      processes. Here, we summarize the main studies about nuclear PI-PLCs,
      specifically the imbalance of isozymes such as PI-PLCbeta1 and PI-PLCzeta, in
      cerebral, hematologic, neuromuscular, and fertility disorders. PI-PLCbeta1 and PI
      PLCgamma1 affect epilepsy, depression, and bipolar disorder. In the brain, PI
      PLCbeta1 is involved in endocannabinoid neuronal excitability and is a
      potentially novel signature gene for subtypes of high-grade glioma. An altered
      quality or quantity of PI-PLCzeta contributes to sperm defects that result in
      infertility, and PI-PLCbeta1 aberrant inositide signaling contributes to both
      hematologic and degenerative muscle diseases. Understanding the mechanisms behind
      PI-PLC involvement in human pathologies may help identify new strategies for
      personalized therapies of these conditions.

PMID- 30287514
TI  - Anatomy and Physiology of the Digestive Tract of Drosophila melanogaster.
AB  - The gastrointestinal tract has recently come to the forefront of multiple
      research fields. It is now recognized as a major source of signals modulating
      food intake, insulin secretion and energy balance. It is also a key player in
      immunity and, through its interaction with microbiota, can shape our physiology
      and behavior in complex and sometimes unexpected ways. The insect intestine had
      remained, by comparison, relatively unexplored until the identification of adult
      somatic stem cells in the Drosophila intestine over a decade ago. Since then, a
      growing scientific community has exploited the genetic amenability of this insect
      organ in powerful and creative ways. By doing so, we have shed light on a broad
      range of biological questions revolving around stem cells and their niches,
      interorgan signaling and immunity. Despite their relatively recent discovery,
      some of the mechanisms active in the intestine of flies have already been shown
      to be more widely applicable to other gastrointestinal systems, and may therefore
      become relevant in the context of human pathologies such as gastrointestinal
      cancers, aging, or obesity. This review summarizes our current knowledge of both
      the formation and function of the Drosophila melanogaster digestive tract, with a
      major focus on its main digestive/absorptive portion: the strikingly adaptable
      adult midgut.

PMID- 30287526
TI  - New Evidence on Carbetocin: Another Arrow in Our Quiver.

PMID- 30287515
TI  - From "the Worm" to "the Worms" and Back Again: The Evolutionary Developmental
      Biology of Nematodes.
AB  - Since the earliest days of research on nematodes, scientists have noted the
      developmental and morphological variation that exists within and between species.
      As various cellular and developmental processes were revealed through intense
      focus on Caenorhabditis elegans, these comparative studies have expanded. Within
      the genus Caenorhabditis, they include characterization of intraspecific
      polymorphisms and comparisons of distinct species, all generally amenable to the
      same laboratory culture methods and supported by robust genomic and experimental
      tools. The C. elegans paradigm has also motivated studies with more distantly
      related nematodes and animals. Combined with improved phylogenies, this work has
      led to important insights about the evolution of nematode development. First,
      while many aspects of C. elegans development are representative of
      Caenorhabditis, and of terrestrial nematodes more generally, others vary in ways
      both obvious and cryptic. Second, the system has revealed several clear examples
      of developmental flexibility in achieving a particular trait. This includes
      developmental system drift, in which the developmental control of homologous
      traits has diverged in different lineages, and cases of convergent evolution.
      Overall, the wealth of information and experimental techniques developed in C.
      elegans is being leveraged to make nematodes a powerful system for evolutionary
      cellular and developmental biology.

PMID- 30287527
TI  - Client Perceptions of Quality and Choice at Static, Mobile Outreach, and Special
      Family Planning Day Services in 3 African Countries.
AB  - BACKGROUND: Use of long-acting reversible contraceptives (LARCs) has grown
      rapidly in the Democratic Republic of the Congo (DRC), Tanzania, and Uganda.
      Uptake of LARCs is particularly high during mobile outreach and special family
      planning day events. It is therefore important to examine client perceptions of
      and experiences with full, free, and informed choice (FFIC) in different service
      delivery modalities. METHODS: Between April and July 2015, we conducted a cross
      sectional family planning client survey to assess FFIC and client satisfaction at
      static, mobile outreach, and special family planning day services in the DRC (n=9
      sites), Tanzania (n=13), and Uganda (n=8). The study investigated clients'
      perceptions across 13 elements of FFIC, including measures of the quality of
      counseling and respondent satisfaction with services across the service delivery
      approaches. Composite FFIC scores were constructed and analyzed as the proportion
      of women who reported affirmatively to all elements and the mean score of
      positive responses. Satisfaction was assessed using a 4-point Likert scale. We
      used logistic regression to assess the association between the primary outcomes
      and mode of service delivery. RESULTS: In total, we interviewed 585 women (n=150
      in Uganda, n=200 in Tanzania, and n=235 in the DRC). The large majority of
      clients in all countries and modalities received their method of choice. Clients
      of mobile outreach and special family planning days preferred LARCs and permanent
      methods, particularly implants, compared with clients at static services.
      Composite measures of FFIC were lower for mobile outreach than for static
      services in Tanzania among all family planning clients (odds ratio [OR]=0.5;
      P<=.001) and among LARC clients specifically (OR=0.5; P<=.01); no significant
      differences were found in the DRC or Uganda. A mean FFIC score among all family
      planning clients showed that clients in all modalities in all countries reported
      experiencing most elements of FFIC, with averages ranging from 4.8 to 6.1 of 7
      elements. Among LARC clients specifically, mean scores ranged from 8.3 to 9.8 of
      11 elements. Where greater proportions of clients experienced higher FFIC,
      greater proportions of clients also tended to report being "very satisfied" with
      aspects of services and counseling. CONCLUSIONS: The results underscore that
      special family planning days and mobile outreach services are important and
      viable ways to increase women's access to family planning services, notably to
      LARCs, but further attention to respecting and fulfilling clients' full, free,
      and informed choice across all service delivery modalities is required.

PMID- 30287528
TI  - Quality and Cost Interventions During the Extended Perinatal Period to Increase
      Family Planning Use in Kinshasa, DRC: Results From an Initial Study.
AB  - BACKGROUND: Most women worldwide do not desire another pregnancy within a year
      after giving birth, but uptake of modern contraception during this time period is
      low. We independently tested 2 approaches to increasing contraceptive uptake and
      the 2 approaches combined using a quasi-experimental study design in Kinshasa,
      the Democratic Republic of the Congo. METHODS: The primary analytic data came
      from client exit interviews conducted post-intervention (N=563) from 4 study
      groups. The first arm (n=150) received free family planning, and the second arm
      (n=113) a quality inputs intervention involving systematic screening, referral,
      and immediate provision of long-acting reversible contraceptives (LARCs) after
      labor and delivery. The third arm (n=150) received a combination of the 2
      interventions, and the fourth (n=150) no intervention. Family planning service
      statistics were also collected throughout the intervention period. RESULTS: Women
      in the quality arm (odds ratio [OR]=4.5; 95% confidence interval [CI], 1.8 to
      10.9) and free/quality arm (OR=6.7; 95% CI, 2.8 to 16.1) were more likely to be
      properly screened for family planning than women in the control group, but paper
      referral was seldom implemented in any group. Women in the free arm (OR=3.8; 95%
      CI, 1.6 to 9.0) and in the free/quality arm (OR=11.0; 95% CI, 4.3 to 27.9) were
      more likely than the control group to report being properly counseled on family
      planning. Clients were more likely to be modern contraceptive users (excluding
      condoms) in the free arm (OR=3.2; 95% CI, 1.4 to 7.2) and in the free/quality arm
      (OR=8.6; 95% CI, 3.9 to 19.0) than in the control group. Clients in all study
      arms were more likely to use a LARC compared with the control group (Quality arm:
      OR=2.9; 95% CI, 1.1 to 7.9. Free arm: OR=5.6; 95% CI, 2.3 to 13.7. Free/quality
      arm: OR=8.4; 95% CI, 3.4 to 20.6). Service statistics from the combined
      intervention arm showed that a significantly greater proportion of family
      planning adoption occurred within the immediate postpartum period (0 to 2 days)
      in the quality arm (P<.001) and free/quality arm (P<.001) than in the control
      arm. Quality inputs, free contraceptives, and the combined intervention had
      positive impacts on aspects of screening and contraceptive uptake. The combined
      intervention performed best by all measures. CONCLUSION: Providing family
      planning, including LARCs, in the immediate postpartum period, implementing a
      systematic screening and referral system, and providing free methods may improve
      family planning access and uptake in the extended perinatal period in this
      environment.

PMID- 30287530
TI  - Global Health Competency Self-Confidence Scale: Tool Development and Validation.
AB  - BACKGROUND: Global health education in tertiary institutions worldwide is at an
      all-time high. Until recently, most evaluations of student learning from a global
      exposure was in the form of a reflective paper with little information that would
      enable standardized assessment of the competencies gained. In 2015, the
      Consortium of Universities for Global Health (CUGH) published a set of
      interprofessional global health competencies that were drawn upon to create a
      Global Health Competency Self-Confidence Scale and workbook. This study reports
      the development and validation of the scale and its implications for global
      health education. METHODS: In total, 126 graduate students from a university in
      New York State participated in the validation process of the Global Health
      Competency Self-Confidence Scale-an 11-domain, 22-item competency self-assessment
      to measure the level of confidence of students before and after undertaking a
      global learning experience. The team used factor analysis to compare the scale to
      the Global Health Competency Survey for content validity and reliability.
      RESULTS: Reliability and validity of the scale was determined. An exploratory
      factor analysis identified 4 standalone components as: (1) Ethical and
      Professional Practice, (2) Capacity Strengthening and Planning, (3) Structural
      and Social Determinants of Health, and (4) Strategic Analysis. The scale showed
      excellent internal consistency (Cronbach's alpha=0.92) and test-retest
      reliability (reliability (r)=0.455; P<.001). Concurrent validity was established.
      CONCLUSION: The Global Health Competency Self-Confidence Scale contributes to a
      further consolidation and refinement of competency groupings into components of
      global health education and offers a scale to assess student learning in global
      placements.

PMID- 30287529
TI  - Role of Religious Leaders in Promoting Contraceptive Use in Nigeria: Evidence
      From the Nigerian Urban Reproductive Health Initiative.
AB  - BACKGROUND: Despite the many supply- and demand-side interventions aimed at
      increasing contraceptive uptake, the modern contraceptive prevalence rate in
      Nigeria has remained very low (9.8%). Religion is an important part of the
      sociocultural fabric of many communities. As such, religious leaders have the
      power to inhibit or facilitate effective adoption of contraceptive methods to
      support family health. We assess the association of exposure to religious
      leaders' tailored scriptural family planning messages with contraceptive use in
      Nigeria. METHODS: This cross-sectional study used data from a Measurement,
      Learning and Evaluation Project survey conducted in 2015 in 4 Nigerian states
      Federal Capital Territory, Kaduna, Kwara, and Oyo. The final study sample was
      restricted to 9,725 non-pregnant women aged 15 to 49 years. Data analysis
      included descriptive statistics and binary logistic regression analysis to
      explore significant relationships between current use of a modern contraceptive
      method, exposure to family planning messages from religious leaders, and selected
      background characteristics. RESULTS: About 2 in 5 women reported being exposed to
      family planning messages from religious leaders in the past year. Bivariate
      results revealed a higher uptake of modern contraceptives among women with high
      exposure to different NURHI interventions (35.5%) compared with respondents in
      the low or medium exposure categories (14.5% and 24.5%, respectively). The
      multivariable analysis revealed significantly higher contraceptive uptake among
      women who had exposure to family planning messages from religious leaders
      relative to those with no exposure (odds ratio=1.70; 95% confidence interval,
      1.54 to 1.87; P<.001). This association remained significant after adjustment for
      background characteristics and other selected variables. CONCLUSION:
      Interventions that engage clerics of different faiths as change agents for
      shaping norms and informing behaviors about family planning and contraceptive use
      are crucial for increasing contraceptive uptake in Nigeria.

PMID- 30287532
TI  - Childbirth and Early Newborn Care Practices in 4 Provinces in China: A Comparison
      With WHO Recommendations.
AB  - OBJECTIVES: As a part of the process of implementing Early Essential Newborn Care
      (EENC) in China, which are evidence-based interventions recommended by the World
      Health Organization (WHO), we sought to understand whether current hospital
      policies are consistent with WHO-recommended standards and what factors influence
      their use. Data from the study will help inform policy changes needed to support
      the introduction of evidence-based childbirth and early newborn care practices
      effectively and to inform further scale up of EENC nationwide. METHODS: Ten
      randomly selected hospitals in 4 early-introducing provinces participated in the
      study. We collected data from 20 simulated delivery scenario observations and
      focus group discussions and individual interviews with 10 hospital management
      staff. Policies, protocols, and guidelines related to childbirth and newborn care
      practice were also collected and reviewed at each hospital. Additionally, a
      survey was emailed to 15 childbirth and newborn experts from the 4 selected
      provinces and completed by 13. Data were compared with WHO EENC evidence-based
      standards to calculate the agreement rates. Barriers to introducing evidence
      based guidelines were identified in focus groups and key informant interviews,
      then combined into common categories. FINDINGS: Hospital policies were not
      consistent with WHO recommendations in 10 (59%) of the 17 delivery and early
      newborn care practices. Delayed cord clamping was recommended by 30% of hospital
      protocols and prolonged skin-to-skin contact by 13%, neither of which were
      observed in the delivery simulations. Kangaroo mother care (KMC) for stable
      preterm babies was required in only 17% of the hospitals; no preterm babies had
      KMC initiated, with all immediately separated from their mothers and admitted to
      neonatal intensive care units. Newborn resuscitation equipment was required to be
      placed within 2 meters of the delivery bed in 84% of hospital protocols, but was
      prepared in only 40% of cases. Immediate drying after birth was required in 48%
      of hospital protocols, but was initiated in only 20% of observed cases.
      CONCLUSIONS: Current childbirth and early newborn care policy and practice in
      China is not aligned with WHO recommendations for some major interventions. To
      make it easier and safer for hospital workers to practice EENC, expert working
      groups and national policies must be established to address inconsistencies and
      cultural beliefs and provide a strong, evidence-based set of guidelines for
      hospitals and health workers to follow.

PMID- 30287531
TI  - Helping Babies Breathe, Second Edition: A Model for Strengthening Educational
      Programs to Increase Global Newborn Survival.
AB  - BACKGROUND: Helping Babies Breathe (HBB), a skills-based program in neonatal
      resuscitation for birth attendants in resource-limited settings, has been
      implemented in over 80 countries since 2010. Implementation studies of HBB
      incorporating low-dose high-frequency practice and quality improvement show
      substantial reductions in fresh stillbirth and first-day neonatal mortality.
      Revision of the program aimed to further augment provider and facilitator skills
      and address gaps in implementation with the goal of improving neonatal survival.
      METHODS: The Utstein Formula for Survival-Medical Science X Educational
      Efficiency X Local Implementation = Survival-provided a framework for the
      revisions. The 2015 Neonatal Resuscitation Consensus on Science and Treatment
      Recommendations by the International Liaison Committee on Resuscitation informed
      scientific updates, which were harmonized with the 2012 World Health Organization
      Basic Newborn Resuscitation Guidelines. Published literature and program reports,
      consensus guidelines on reprocessing equipment, systematic collection of
      suggestions from frontline users, and responses to a semistructured online
      questionnaire informed educational/implementation revisions. Links to maternal
      care were added. Draft materials underwent Delphi review and field testing in
      India and Sierra Leone. An Utstein-style meeting of stakeholders identified key
      actions for successful implementation. RESULTS: Scientific revisions included
      expectant management of infants with meconium-stained amniotic fluid, limitation
      of suctioning, and initiating and continuing effective ventilation until
      spontaneous respirations. Frontline users (N=102) suggested augmented simulation
      methods to build confidence and competence and additional guidance for
      facilitators on implementation. Users identified a need for sufficient practice
      during the workshop, systematized ongoing practice, and enough simulators for
      participants. Field trials refined approaches to self-reflection, feedback and
      debriefing, and quality improvement. Utstein meeting stakeholders validated the
      importance of quality improvement and use of data to improve outcomes.
      CONCLUSIONS: The second edition of HBB provides a newer paradigm of learning for
      providers that incorporates workshop practice, self-reflection, and feedback and
      debriefing to reinforce learning as well as the promotion of mentorship and
      development of facilitators, systems for low-dose high-frequency practice in
      facilities, and quality improvement related to neonatal resuscitation.

PMID- 30287533
TI  - Local Sourcing and Supplier Development in Global Health: Analysis of the Supply
      Chain Management System's Local Procurement in 4 Countries.
AB  - From 2006 to 2014, Supply Chain Management System (SCMS), the global procurement
      and distribution project for the U.S. President's Emergency Plan for AIDS Relief
      (PEPFAR), distributed over US$1.6 billion worth of antiretroviral drugs and other
      health commodities, with over US$263 million purchased from local vendors in 14
      countries in sub-Saharan Africa. A simple framework was developed and 39 local
      suppliers from 4 countries were interviewed between 2013 and 2014 to understand
      how SCMS local sourcing impacted supplier development. SCMS local suppliers
      reported new contracts with other businesses (77%), new assets acquired (67%),
      increased access to capital from local lending institutions (75%), offering more
      products and services (92%), and ability to negotiate better prices from their
      principles (80%). Additionally, 70% (n=27) of the businesses hired between 1 and
      30 new employees after receiving their first SCMS contract and 15% (n=6) hired
      between 30 and 100 new employees. This study offers preliminary guidance on how
      bilateral and multilateral agencies could design effective local sourcing
      programs to create sustainable local markets for selected pharmaceutical
      products, laboratory, and transport services.

PMID- 30287534
TI  - Decentralized, Community-Based Treatment for Drug-Resistant Tuberculosis:
      Bangladesh Program Experience.
AB  - BACKGROUND: Bangladesh is a highly populous country where the prevalence of drug
      resistant tuberculosis (DR-TB) is growing. With the rapid increase in DR-TB
      notifications through GeneXpert technology, it was imperative to come up with a
      new treatment strategy that could keep up with the increase of patients
      diagnosed. INTERVENTION: Intervention was designed to support national transition
      of DR-TB management of World Health Organization-approved long course (20-to-24
      month regimen) treatment from a hospital-based approach to the decentralized
      model of community-based programmatic management of DR-TB (cPMDT). In close
      coordination with the Ministry of Health and Family Welfare and National TB
      Program, patients were initiated into treatment at hospitals and then transferred
      to community-based care. A cadre of directly observed therapy providers supported
      treatment at the household level, supervised by the outpatient DR-TB teams.
      METHODS: We conducted a descriptive pre- and post-intervention study of all 1,946
      DR-TB patients enrolled in treatment nationwide between May 2012 and June 2015.
      Data were collected from hospitals, patient cards, district records, and
      diagnostic laboratories through the National TB Program. Intervention results
      were assessed in comparison with the baseline (2011) indicators. RESULTS: During
      the intervention period, treatment enrollment of 1,946 diagnosed DR-TB patients
      through the national program increased from 50% in 2011 to 100% in 2015. The
      delay between diagnosis and treatment initiation decreased from 69 days in 2011
      to 6 days in 2014. Most (95%) of the patients completed all scheduled follow-up
      smear and culture tests. By the sixth month of treatment, 99% of patients had
      negative smear conversion and 98% had negative culture conversion. The treatment
      success rate increased from 70% in 2011 to 76% in 2015 at the end of the
      intervention period. The results also indicate a decline between baseline and end
      line from 34% to 9% for patients died, 34% to 10% for loss to follow-up, and 1.7%
      to 0% for treatment failure. CONCLUSIONS: Community-based management is an
      effective approach for increasing access to quality-assured DR-TB treatment.
      Using existing structures and resources, the intervention demonstrated that
      favorable treatment outcomes can be achieved and sustained by treating patients
      with DR-TB at their homes.

PMID- 30287536
TI  - Update of: Sarma et al., Effectiveness of SMS Technology on Timely Community
      Health Worker Follow-Up for Childhood Malnutrition: A Retrospective Cohort Study
      in sub-Saharan Africa.

PMID- 30287535
TI  - Menstrual Bleeding Changes Are NORMAL: Proposed Counseling Tool to Address Common
      Reasons for Non-Use and Discontinuation of Contraception.

PMID- 30287537
TI  - Update of: Kheang et al., Malaria Case Detection Among Mobile Populations and
      Migrant Workers in Myanmar: Comparison of 3 Service Delivery Approaches.

PMID- 30287538
TI  - Update of: Ouedraogo et al., Expanding the Single-Visit Approach for Cervical
      Cancer Prevention: Successes and Lessons From Burkina Faso.

PMID- 30287539
TI  - Update of: Harvey, Observe Before You Leap: Why Observation Provides Critical
      Insights for Formative Research and Intervention Design That You'll Never Get
      From Focus Groups, Interviews, or KAP Surveys.

PMID- 30287540
TI  - Update of: Ndiaye et al., High-Risk Advanced Maternal Age and High Parity
      Pregnancy: Tackling a Neglected Need Through Formative Research and Action.

PMID- 30287542
TI  - Update of: Subramanian et al., Increasing Contraceptive Use Among Young Married
      Couples in Bihar, India: Evidence From a Decade of Implementation of the PRACHAR
      Project.

PMID- 30287541
TI  - Update of: Marks et al., Review of Grain Fortification Legislation, Standards,
      and Monitoring Documents.

PMID- 30287543
TI  - Update of: Koffi et al., Engaging Men in Family Planning: Perspectives From
      Married Men in Lome, Togo.

PMID- 30287544
TI  - Update of: Choi and Short Fabic, Monitoring Progress in Equality for the
      Sustainable Development Goals: A Case Study of Meeting Demand for Family
      Planning.

PMID- 30287545
TI  - Empowering clinicians to complain about system failures.

PMID- 30287546
TI  - Quantitative proteomics identification of seminal fluid proteins in male
      Drosophila melanogaster.
AB  - Seminal fluid contains some of the fastest evolving proteins currently known.
      These seminal fluid proteins (Sfps) play crucial roles in reproduction, such as
      supporting sperm function, and particularly in insects, modifying female
      physiology and behaviour. Identification of Sfps in small animals is challenging,
      and often relies on samples taken from the female reproductive tract after
      mating. A key pitfall of this method is that it might miss Sfps that are of low
      abundance due to dilution in the female-derived sample or rapid processing in
      females. Here we present a new and complementary method, which provides added
      sensitivity to Sfp identification. We applied label-free quantitative proteomics
      to Drosophila melanogaster male reproductive tissue - where Sfps are unprocessed,
      and highly abundant - and quantified Sfps before and immediately after mating, to
      infer those transferred during copulation. We also analysed female reproductive
      tracts immediately before and after copulation to confirm the presence and
      abundance of known and candidate Sfps, where possible. Results were cross
      referenced with transcriptomic and sequence databases to improve confidence in
      Sfp detection. Our data were consistent with 125 previously reported Sfps. We
      found nine high-confidence novel candidate Sfps, which were both depleted in
      mated versus unmated males and identified within the reproductive tract of mated
      but not virgin females. We also identified 42 more candidates that are likely
      Sfps based on their abundance, known expression and predicted characteristics,
      and revealed that four proteins previously identified as Sfps are at best minor
      contributors to the ejaculate. The estimated copy numbers for our candidate Sfps
      were lower than for previously identified Sfps, supporting the idea that our
      technique provides a deeper analysis of the Sfp proteome than previous studies.
      Our results demonstrate a novel, high-sensitivity approach to the analysis of
      seminal fluid proteomes, whose application will further our understanding of
      reproductive biology.

PMID- 30287547
TI  - Validation of the 12-gene Predictive Signature for Adjuvant Chemotherapy Response
      in Lung Cancer.
AB  - Purpose: Response to adjuvant chemotherapy after tumor resection varies widely
      among patients with non-small cell lung cancer (NSCLC); therefore, it is of
      clinical importance to prospectively predict who will benefit from adjuvant
      chemotherapy before starting the treatment. The goal of this study is to validate
      a 12-gene adjuvant chemotherapy predictive signature developed from a previous
      study using a clinical-grade assay.Experimental Design: We developed a clinical
      grade assay for formalin-fixed, paraffin-embedded (FFPE) samples using the
      NanoString nCounter platform to measure the mRNA expression of the previously
      published 12-gene set. The predictive performance was validated in a cohort of
      207 patients with early-stage resected NSCLC with matched propensity score of
      adjuvant chemotherapy.Results: The effects of adjuvant chemotherapy were
      significantly different in patients from the predicted adjuvant chemotherapy
      benefit group and those in the predicted adjuvant chemotherapy nonbenefit group
      (P = 0.0056 for interaction between predicted risk group and adjuvant
      chemotherapy). Specifically, in the predicted adjuvant chemotherapy benefit
      group, the patients receiving adjuvant chemotherapy had significant recurrence
      free survival (RFS) benefit (HR = 0.34; P = 0.016; adjuvant chemotherapy vs.
      nonadjuvant chemotherapy), while in the predicted adjuvant chemotherapy
      nonbenefit group, the patients receiving adjuvant chemotherapy actually had worse
      RFS (HR = 1.86; P = 0.14; adjuvant chemotherapy vs. nonadjuvant chemotherapy)
      than those who did not receive adjuvant chemotherapy.Conclusions: This study
      validated that the 12-gene signature and the FFPE-based clinical assay predict
      that patients whose resected lung adenocarcinomas exhibit an adjuvant
      chemotherapy benefit gene expression pattern and who then receive adjuvant
      chemotherapy have significant survival advantage compared with patients whose
      tumors exhibit the benefit pattern but do not receive adjuvant chemotherapy. Clin
      Cancer Res; 1-8. (c)2018 AACR.

PMID- 30287548
TI  - Arrested Developments: CDK4/6 Inhibitor Resistance and Alterations in the Tumor
      Immune Microenvironment.
AB  - The uncontrolled proliferation of cancer cells has led to the development of
      small-molecule inhibitors to target cell-cycle progression. Palbociclib,
      ribociclib, and abemaciclib are ATP-competitive inhibitors of cyclin-dependent
      kinases 4/6 (CDK4/6), which function early within the G1 phase of the cell cycle.
      Recently, CDK4/6 inhibitors have gained FDA approval in postmenopausal estrogen
      receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative
      breast cancer and testing in other cancer types is underway. However, resistance
      to CDK4/6 inhibitors frequently develops. In addition, targeting CDK4/6 may
      augment the action of immune checkpoint blockade agents. Here, we review recent
      studies that provide the preclinical rationale for treatment combinations and
      schedules that include CDK4/6 inhibitors. Furthermore, we discuss inhibitor
      effects on tumor-infiltrating lymphocytes as a preclinical rationale for
      targeting CDK4/6 in combination with anti-PD-1 or anti-CTLA-4 antibodies. Clin
      Cancer Res; 1-7. (c)2018 AACR.

PMID- 30287549
TI  - Clinical Significance of Extracellular Vesicles in Plasma from Glioblastoma
      Patients.
AB  - Purpose: Glioblastoma (GBM) is the most common primary brain tumor. The
      identification of blood biomarkers reflecting the tumor status represents a major
      unmet need for optimal clinical management of patients with GBM. Their high
      number in body fluids, their stability, and the presence of many tumor-associated
      proteins and RNAs make extracellular vesicles potentially optimal biomarkers.
      Here, we investigated the potential role of plasma extracellular vesicles from
      patients with GBM for diagnosis and follow-up after treatment and as a prognostic
      tool.Experimental Design: Plasma from healthy controls (n = 33), patients with
      GBM (n = 43), and patients with different central nervous system malignancies (n
      = 25) were collected. Extracellular vesicles were isolated by ultracentrifugation
      and characterized in terms of morphology by transmission electron microscopy,
      concentration, and size by nanoparticle tracking analysis, and protein
      composition by mass spectrometry. An orthotopic mouse model of human GBM
      confirmed human plasma extracellular vesicle quantifications. Associations
      between plasma extracellular vesicle concentration and clinicopathologic features
      of patients with GBM were analyzed. All statistical tests were two-sided.Results:
      GBM releases heterogeneous extracellular vesicles detectable in plasma. Plasma
      extracellular vesicle concentration was higher in GBM compared with healthy
      controls (P < 0.001), brain metastases (P < 0.001), and extra-axial brain tumors
      (P < 0.001). After surgery, a significant drop in plasma extracellular vesicle
      concentration was measured (P < 0.001). Plasma extracellular vesicle
      concentration was also increased in GBM-bearing mice (P < 0.001). Proteomic
      profiling revealed a GBM-distinctive signature.Conclusions: Higher extracellular
      vesicle plasma levels may assist in GBM clinical diagnosis: their reduction after
      GBM resection, their rise at recurrence, and their protein cargo might provide
      indications about tumor, therapy response, and monitoring. Clin Cancer Res; 1-11.
      (c)2018 AACR.

PMID- 30287552
TI  - A non-vet role to help exports is 'acceptable'.

PMID- 30287551
TI  - Can the UK go global in its search for vets?

PMID- 30287559
TI  - Deer in Michigan and the spread of bovine TB.
AB  - Matthew Limb reports on how one species in one state is hampering bovine TB
      eradication in the USA.

PMID- 30287550
TI  - High-salt-recovered sequences are associated with the active chromosomal
      compartment and with large ribonucleoprotein complexes including nuclear bodies.
AB  - The mammalian cell nucleus contains numerous discrete suborganelles named nuclear
      bodies. While recruitment of specific genomic regions into these large
      ribonucleoprotein (RNP) complexes critically contributes to higher-order
      functional chromatin organization, such regions remain ill-defined. We have
      developed the high-salt-recovered sequences-sequencing (HRS-seq) method, a
      straightforward genome-wide approach whereby we isolated and sequenced genomic
      regions associated with large high-salt insoluble RNP complexes. By using mouse
      embryonic stem cells (ESCs), we showed that these regions essentially correspond
      to the most highly expressed genes, and to cis-regulatory sequences like super
      enhancers, that belong to the active A chromosomal compartment. They include both
      cell-type-specific genes, such as pluripotency genes in ESCs, and housekeeping
      genes associated with nuclear bodies, such as histone and snRNA genes that are
      central components of Histone Locus Bodies and Cajal bodies. We conclude that
      HRSs are associated with the active chromosomal compartment and with large RNP
      complexes including nuclear bodies. Association of such chromosomal regions with
      nuclear bodies is in agreement with the recently proposed phase separation model
      for transcription control and might thus play a central role in organizing the
      active chromosomal compartment in mammals.

PMID- 30287560
TI  - Celebrating excellence in equine medicine.

PMID- 30287561
TI  - Medicines update.

PMID- 30287562
TI  - Disease surveillance in England and Wales, September 2018.

PMID- 30287563
TI  - Streptococcus suis disease in pigs.
AB  - This article was prepared by Susanna Williamson, Veterinary Lead of the APHA Pig
      Expert Group.

PMID- 30287564
TI  - If only they could talk ....

PMID- 30287566
TI  - Advocating for the pit bull 'type' dog.

PMID- 30287567
TI  - Nigel Taylor responds.

PMID- 30287568
TI  - Hunting hounds and bovine TB.

PMID- 30287569
TI  - Hunting hounds and bovine TB.

PMID- 30287570
TI  - Welfare of poultry during transport.

PMID- 30287571
TI  - Live exports of calves.

PMID- 30287573
TI  - Let us celebrate the 'art' of veterinary work.

PMID- 30287583
TI  - From practice to PhD: how a passion for cats led to ground-breaking research.
AB  - Vet Nathalie Dowgray graduated from Massey University in 2002 and came to the UK
      to work in practice. She is currently undertaking a PhD at Liverpool university
      looking at ageing in cats.

PMID- 30287584
TI  - New qualifications in canine hydrotherapy.

PMID- 30287585
TI  - Trafficking of ciliary membrane proteins by the intraflagellar transport/BBSome
      machinery.
AB  - Bardet-Biedl syndrome (BBS) is a rare inherited disease caused by defects in the
      BBSome, an octameric complex of BBS proteins. The BBSome is conserved in most
      organisms with cilia, which are microtubule (MT)-based cell organelles that
      protrude from the cell surface and function in motility and sensing. Cilia
      assembly, maintenance, and function require intraflagellar transport (IFT), a
      bidirectional motility of multi-megadalton IFT trains propelled by molecular
      motors along the ciliary MTs. IFT has been shown to transport structural
      proteins, including tubulin, into growing cilia. The BBSome is an adapter for the
      transport of ciliary membrane proteins and cycles through cilia via IFT. While
      both the loss and the abnormal accumulation of ciliary membrane proteins have
      been observed in bbs mutants, recent data converge on a model where the BBSome
      mainly functions as a cargo adapter for the removal of certain transmembrane and
      peripheral membrane proteins from cilia. Here, we review recent data on the
      ultrastructure of the BBSome and how the BBSome recognizes its cargoes and
      mediates their removal from cilia.

PMID- 30287586
TI  - Systems biology primer: the basic methods and approaches.
AB  - Systems biology is an integrative discipline connecting the molecular components
      within a single biological scale and also among different scales (e.g. cells,
      tissues and organ systems) to physiological functions and organismal phenotypes
      through quantitative reasoning, computational models and high-throughput
      experimental technologies. Systems biology uses a wide range of quantitative
      experimental and computational methodologies to decode information flow from
      genes, proteins and other subcellular components of signaling, regulatory and
      functional pathways to control cell, tissue, organ and organismal level
      functions. The computational methods used in systems biology provide systems
      level insights to understand interactions and dynamics at various scales, within
      cells, tissues, organs and organisms. In recent years, the systems biology
      framework has enabled research in quantitative and systems pharmacology and
      precision medicine for complex diseases. Here, we present a brief overview of
      current experimental and computational methods used in systems biology.

PMID- 30287587
TI  - Measuring microtubule dynamics.
AB  - Microtubules are key players in cellular self-organization, acting as structural
      scaffolds, cellular highways, force generators and signalling platforms.
      Microtubules are polar filaments that undergo dynamic instability, i.e.
      transition between phases of growth and shrinkage. This allows microtubules to
      explore the inner space of the cell, generate pushing and pulling forces and
      remodel themselves into arrays with different geometry and function such as the
      mitotic spindle. To do this, eukaryotic cells employ an arsenal of regulatory
      proteins to control microtubule dynamics spatially and temporally. Plants and
      microorganisms have developed secondary metabolites that perturb microtubule
      dynamics, many of which are in active use as cancer chemotherapeutics and anti
      inflammatory drugs. Here, we summarize the methods used to visualize microtubules
      and to measure the parameters of dynamic instability to study both microtubule
      regulatory proteins and the action of small molecules interfering with
      microtubule assembly and/or disassembly.

PMID- 30287589
TI  - The low-down on sleeping down low: pigeons shift to lighter forms of sleep when
      sleeping near the ground.
AB  - Sleep in birds is composed of two distinct sub-states, remarkably similar to
      mammalian slow-wave sleep (SWS) and rapid eye movement (REM) sleep. However, it
      is unclear whether all aspects of mammalian sleep are present in birds. We
      examined whether birds suppress REM sleep in response to changes in sleeping
      conditions that presumably evoke an increase in perceived predation risk, as
      observed previously in rodents. Although pigeons sometimes sleep on the ground,
      they prefer to sleep on elevated perches at night, probably to avoid nocturnal
      mammalian ground predators. Few studies to date have investigated how roosting
      sites affect sleep architecture. We compared sleep in captive pigeons on days
      with and without access to high perches. On the first (baseline) day, low and
      high perches were available; on the second day, the high perches were removed;
      and on the third (recovery) day, the high perches were returned. The total time
      spent sleeping did not vary significantly between conditions; however, the time
      spent in REM sleep declined on the low-perch night and increased above baseline
      when the pigeons slept on the high perch during the recovery night. Although the
      amount of SWS did not vary significantly between conditions, SWS intensity was
      lower on the low-perch night, particularly early in the night. The similarity of
      these responses between birds and mammals suggests that REM sleep is influenced
      by at least some ecological factors in a similar manner in both groups of
      animals.

PMID- 30287588
TI  - Barriers and Facilitators to Asthma Care After Hospitalization as Reported by
      Caregivers, Health Providers, and School Nurses.
AB  - OBJECTIVES: To develop a comprehensive understanding of the barriers and/or
      facilitators for asthma management for the health professionals and caregivers of
      children with >1 hospitalization. METHODS: Individual interviews were conducted
      with family caregivers and health professionals. Focus groups were conducted with
      school nurses. The interview and focus group guide were used to probe for
      barriers and facilitators of asthma management. Interviews were recorded,
      transcribed, and coded by using qualitative software. Themes were identified by
      using content analysis in the interviews and descriptive qualitative analysis in
      the focus groups. RESULTS: Caregivers (n = 10), asthma educators (n = 4),
      physicians (n = 4), and a payer (n = 1) were individually interviewed. School
      nurses were interviewed via a focus group (n = 10). Children had a median age of
      7 years, mean length of stay of 1.9 days, and 56% had a previous hospitalization
      in the previous 12 months. The "gaps in asthma knowledge" theme (which includes
      an inadequate understanding of asthma chronicity, activity restrictions, and
      management with controller medications) emerged as a theme for both caregivers
      and health professionals but with different health beliefs. School nurses
      reinforced the difficulty they have in managing children who have asthma in
      schools, and they identified using the asthma action plan as a facilitator.
      CONCLUSIONS: Caregivers and health professionals have different health beliefs
      about asthma knowledge, which raises challenges in the care of a child who has
      asthma. In addition, school nurses highlight specific barriers that are focused
      on medication use in schools. A comprehensive understanding of the barriers and
      facilitators of asthma management that families experience after hospital
      discharge is crucial to design better efforts to support families.

PMID- 30287590
TI  - Invertebrate serotonin receptors: a molecular perspective on classification and
      pharmacology.
AB  - Invertebrate receptors for the neurotransmitter serotonin (5-HT) have been
      identified in numerous species from diverse phyla, including Arthropoda,
      Mollusca, Nematoda and Platyhelminthes. For many receptors, cloning and
      characterization in heterologous systems have contributed data on molecular
      structure and function across both closely and distantly related species. This
      article provides an overview of heterologously expressed receptors, and considers
      evolutionary relationships among them, classification based on these
      relationships and nomenclature that reflects classification. In addition,
      transduction pathways and pharmacological profiles are compared across receptor
      subtypes and species. Previous work has shown that transduction mechanisms are
      well conserved within receptor subtypes, but responses to drugs are complex. A
      few ligands display specificity for different receptors within a single species;
      however, none acts with high specificity in receptors across different species.
      Two non-selective vertebrate ligands, the agonist 5-methoxytryptamine and
      antagonist methiothepin, are active in most receptor subtypes in multiple species
      and hence bind very generally to invertebrate 5-HT receptors. Future challenges
      for the field include determining how pharmacological profiles are affected by
      differences in species and receptor subtype, and how function in heterologous
      receptors can be used to better understand 5-HT activity in intact organisms.

PMID- 30287592
TI  - A 17-Year-Old Girl With Weight Loss and Elevated Inflammatory Markers.
AB  - A 17-year-old girl presented to her primary care physician with a history of
      unintentional weight loss and vague sensory symptoms, including tingling of her
      lower extremities. She had a nonrevealing neurology workup and a largely normal
      rheumatology workup apart from mild elevation in her inflammatory markers. She
      also had a nonfocal examination apart from a posterior cervical lymph node (2 * 1
      cm). Given that she was well appearing, with a nonfocal examination and only mild
      laboratory abnormalities, she was told to follow-up with rheumatology in 3
      months. Around that time, she re-presented to her medical home for a well-child
      visit, during which she was noted to have continued weight loss, now amounting to
      17 lb in 1 year, and marked further elevation in her inflammatory markers. Her
      laboratory results were also significant for a profound microcytic anemia
      requiring inpatient admission for blood transfusion. During her admission, she
      was seen by the rheumatology, gastroenterology, and oncology subspecialty teams.
      Despite imaging studies and extensive laboratory workup, there was no unifying
      diagnosis at the time of her hospital discharge. Ultimately, an outpatient
      imaging study revealed the etiology.

PMID- 30287591
TI  - Activity Performance Curves of Individuals With Cerebral Palsy.
AB  - : : media-1vid110.1542/5804911840001PEDS-VA_2017-3723Video Abstract OBJECTIVES:
      Describe development curves of motor and daily activity performance in
      individuals with cerebral palsy (CP). METHODS: Participants with CP aged 1 to 20
      years at baseline (n = 421) and Gross Motor Functioning Classification System
      (GMFCS) levels I to V (27% of participants with intellectual disability [ID])
      were longitudinally assessed up to a 13-year follow-up period. Motor and daily
      activity performance were assessed using the relevant subdomains of the Vineland
      Adaptive Behavior Scales survey. Nonlinear mixed effects analyses were used,
      estimating the limit (average maximal performance level) and the age by which
      individuals reached 90% of the limit (age90). RESULTS: Limits of motor
      performance decreased with each lower functional level. Age90 for motor
      performance was reached at ~6 to 8 years of age in children with GMFCS levels I
      to III, and at younger ages in those with lower functional levels. Limits of
      daily activity performance did not differ between individuals without ID with
      GMFCS levels I to III. The age90s of daily activities were reached between 11 and
      14 (personal), 26 and 32 (domestic), and 22 and 26 years of age (community).
      Individuals with ID reached lower daily activity performance limits earlier.
      CONCLUSIONS: Individuals with CP continue to develop motor performance after
      gross motor capacity limits are reached. For those without ID, daily activities
      continue to develop into their 20s. Individuals who are severely affected
      functionally have the least favorable development of motor performance, and those
      with ID have the least favorable development of daily activity performance.

PMID- 30287594
TI  - PEHO syndrome: the endpoint of different genetic epilepsies.
AB  - BACKGROUND: Progressive encephalopathy, hypsarrhythmia and optic atrophy (PEHO)
      has been described as a clinically distinct syndrome. It has been postulated that
      it is an autosomal recessive condition. However, the aetiology is poorly
      understood, and the genetic basis of the condition has not been fully elucidated.
      Our objective was to discover if PEHO syndrome is a single gene disorder. METHOD:
      Children with PEHO and PEHO-like syndrome were recruited. Clinical, neurological
      and dysmorphic features were recorded; EEG reports and MRI scans were reviewed.
      Where possible, exome sequencing was carried out first to seek mutations in known
      early infantile developmental and epileptic encephalopathy (DEE) genes and then
      to use an agnostic approach to seek novel candidate genes. We sought intra
      interfamilial phenotypic correlations and genotype-phenotype correlations when
      pathological mutations were identified. RESULTS: Twenty-three children were
      recruited from a diverse ethnic background, 19 of which were suitable for
      inclusion. They were similar in many of the core and the supporting features of
      PEHO, but there was significant variation in MRI and ophthalmological findings,
      even between siblings with the same mutation. A pathogenic genetic variant was
      identified in 15 of the 19 children. One further girl's DNA failed analysis, but
      her two affected sisters shared confirmed variants. Pathogenic variants were
      identified in seven different genes. CONCLUSIONS: We found significant clinical
      and genetic heterogeneity. Given the intrafamily variation demonstrated, we
      question whether the diagnostic criteria for MRI and ophthalmic findings should
      be altered. We also question whether PEHO and PEHO-like syndrome represent
      differing points on a clinical spectrum of the DEE. We conclude that PEHO and
      PEHO-like syndrome are clinically and genetically diverse entities-and are
      phenotypic endpoints of many severe genetic encephalopathies.

PMID- 30287593
TI  - 16p13.11 microduplication in 45 new patients: refined clinical significance and
      genotype-phenotype correlations.
AB  - BACKGROUND: The clinical significance of 16p13.11 duplications remains
      controversial while frequently detected in patients with developmental delay
      (DD), intellectual deficiency (ID) or autism spectrum disorder (ASD). Previously
      reported patients were not or poorly characterised. The absence of consensual
      recommendations leads to interpretation discrepancy and makes genetic counselling
      challenging. This study aims to decipher the genotype-phenotype correlations to
      improve genetic counselling and patients' medical care. METHODS: We
      retrospectively analysed data from 16 013 patients referred to 12 genetic centers
      for DD, ID or ASD, and who had a chromosomal microarray analysis. The referring
      geneticists of patients for whom a 16p13.11 duplication was detected were asked
      to complete a questionnaire for detailed clinical and genetic data for the
      patients and their parents. RESULTS: Clinical features are mainly speech delay
      and learning disabilities followed by ASD. A significant risk of cardiovascular
      disease was noted. About 90% of the patients inherited the duplication from a
      parent. At least one out of four parents carrying the duplication displayed a
      similar phenotype to the propositus. Genotype-phenotype correlations show no
      impact of the size of the duplicated segment on the severity of the phenotype.
      However, NDE1 and miR-484 seem to have an essential role in the neurocognitive
      phenotype. CONCLUSION: Our study shows that 16p13.11 microduplications are likely
      pathogenic when detected in the context of DD/ID/ASD and supports an essential
      role of NDE1 and miR-484 in the neurocognitive phenotype. Moreover, it suggests
      the need for cardiac evaluation and follow-up and a large study to evaluate the
      aortic disease risk.

PMID- 30287595
TI  - Mosaicism and incomplete penetrance of PCDH19 mutations.
AB  - BACKGROUND: Mutations in the PCDH19 gene have mainly been reported in female
      patients with epilepsy. To date, PCDH19 mutations have been reported in hundreds
      of females and only in 10 mosaic male epileptic patients with mosaicism.
      OBJECTIVE: We aimed to investigate the occurrence of mosaic PCDH19 mutations in
      42 families comprising at least one patient with PCDH19-related epilepsy.
      METHODS: Two male patients with mosaic PCDH19 variants were identified using
      targeted next-generation sequencing. Forty female patients with PCDH19 variants
      were identified by Sanger sequencing and Multiple Ligation Probe Amplification
      (MLPA). Microdroplet digital PCR was used to quantify the mutant allelic
      fractions (MAFs) in 20 families with PCDH19 variants. RESULTS: Five mosaic
      individuals, four males and one female, were identified in total. Mosaic variant
      was confirmed in multiple somatic tissues from one male patient and in blood from
      the other male patient. Among 22 female patients harbouring a newly occurred
      PCDH19 variant identified by Sanger sequencing and MLPA, Sanger sequencing
      revealed two mosaic fathers (9%, 2/22), one with two affected daughters and the
      other with an affected child. Two asymptomatic mosaic fathers were confirmed as
      gonosomal mosaicism, with MAFs ranging from 4.16% to 37.38% and from 1.27% to
      19.13%, respectively. In 11 families with apparent de novo variants, 1 female
      patient was identified as a mosaic with a blood MAF of 26.72%. CONCLUSION: Our
      study provides new insights into phenotype-genotype correlations in PCDH19
      related epilepsy and the finding of high-frequency mosaicism has important
      implications for genetic counselling.

PMID- 30287596
TI  - Haemophagocytic lymphohistiocytosis complicating pembrolizumab treatment for
      metastatic breast cancer in a patient with the PRF1A91V gene polymorphism.
AB  - BACKGROUND: Immune checkpoint inhibitor therapy is a modern breakthrough in
      medical oncology, but it can precipitate inflammatory and autoimmune adverse
      effects. Among the most serious of these toxicities is haemophagocytic
      lymphohistiocytosis (HLH), a life-threatening disorder of unbridled immune
      activation that results in injury to multiple organ systems. OBJECTIVE:
      Description of a case of pembrolizumab-associated HLH in a patient with a
      proposed underlying genetic risk factor for its occurrence. METHODS AND RESULTS:
      We describe a patient with aggressive metastatic breast cancer who developed HLH
      while undergoing experimental treatment with pembrolizumab, resulting in critical
      illness and multiorgan system failure. Pembrolizumab discontinuation and high
      dose corticosteroids were effective in managing HLH. Subsequent next-generation
      sequencing of 15 genes associated with HLH revealed a germline polymorphism in
      perforin-1 (PRF1), PRFA91V, that may have predisposed the patient to develop HLH.
      The patient has had no evidence of malignancy for 2 years following recovery
      despite receiving no further cancer-directed treatment. CONCLUSIONS: HLH is a
      rare but serious complication of immune checkpoint blockade. Patients with
      underlying hypomorphic alleles in PRF1 may be predisposed to develop this
      toxicity. Further studies are necessary to confirm a possible link between
      perforin gene mutations and immune checkpoint blockade-associated HLH.

PMID- 30287598
TI  - Correction: A common SLC26A4-linked haplotype underlying non-syndromic hearing
      loss with enlargement of the vestibular aqueduct.

PMID- 30287599
TI  - Investigation of clinically relevant germline variants detected by next
      generation sequencing in patients with childhood cancer: a review of the
      literature.
AB  - Genetic predisposition is an important underlying cause of childhood cancer,
      although the proportion of patients with childhood cancer carrying predisposing
      pathogenic germline variants is uncertain. This review considers the pathogenic
      or likely pathogenic germline variants reported by six studies that used next
      generation sequencing to investigate genetic predisposition in selected cohorts
      of patients with childhood cancer and used incompletely overlapping gene sets for
      analysis and interpretation. These six studies reported that 8.5%-35.5% of
      patients with childhood cancer carried clinically relevant germline variants.
      Analysis of 52 autosomal dominant cancer predisposition genes assumed common to
      all six studies showed that 5.5%-25.8% of patients with childhood cancer carried
      pathogenic or likely pathogenic germline variants in at least one of these genes.
      When only non-central nervous system solid tumours (excluding adrenocortical
      carcinomas) were considered, 8.5%-10.3% of the patients carried pathogenic or
      likely pathogenic germline variants in at least one of 52 autosomal dominant
      cancer predisposition genes. There was a lack of concordance between the genotype
      and phenotype in 33.3%-57.1% of the patients reported with pathogenic or likely
      pathogenic germline variants, most of which represented variants in autosomal
      dominant cancer predisposition genes associated with adult onset cancers. In
      summary, germline genetic testing in patients with childhood cancer requires
      clear definition of phenotypes and genes considered for interpretation, with
      potential to inform and broaden childhood cancer predisposition syndromes.

PMID- 30287597
TI  - Progression from islet autoimmunity to clinical type 1 diabetes is influenced by
      genetic factors: results from the prospective TEDDY study.
AB  - BACKGROUND: Progression time from islet autoimmunity to clinical type 1 diabetes
      is highly variable and the extent that genetic factors contribute is unknown.
      METHODS: In 341 islet autoantibody-positive children with the human leucocyte
      antigen (HLA) DR3/DR4-DQ8 or the HLA DR4-DQ8/DR4-DQ8 genotype from the
      prospective TEDDY (The Environmental Determinants of Diabetes in the Young)
      study, we investigated whether a genetic risk score that had previously been
      shown to predict islet autoimmunity is also associated with disease progression.
      RESULTS: Islet autoantibody-positive children with a genetic risk score in the
      lowest quartile had a slower progression from single to multiple autoantibodies
      (p=0.018), from single autoantibodies to diabetes (p=0.004), and by trend from
      multiple islet autoantibodies to diabetes (p=0.06). In a Cox proportional hazards
      analysis, faster progression was associated with an increased genetic risk score
      independently of HLA genotype (HR for progression from multiple autoantibodies to
      type 1 diabetes, 1.27, 95% CI 1.02 to 1.58 per unit increase), an earlier age of
      islet autoantibody development (HR, 0.68, 95% CI 0.58 to 0.81 per year increase
      in age) and female sex (HR, 1.94, 95% CI 1.28 to 2.93). CONCLUSIONS: Genetic risk
      scores may be used to identify islet autoantibody-positive children with high
      risk HLA genotypes who have a slow rate of progression to subsequent stages of
      autoimmunity and type 1 diabetes.

PMID- 30287600
TI  - Preventive effect of oral magnesium in postmastectomy pain: protocol for a
      randomised, double-blind, controlled clinical trial.
AB  - INTRODUCTION: Breast cancer affects 1 in 10 women worldwide, and mastectomy is a
      cause of chronic pain with neuropathic characteristics. N-methyl-D-aspartate
      receptor (NMDAR) antagonists such as ketamine, memantine, dextromethorphan or
      magnesium are used to treat refractory pain by blocking NMDAR. Oral memantine has
      been shown to prevent postmastectomy pain and cognitive impact and to maintain
      quality of life. Likewise, the present study is intended to assess the preventive
      effect of oral magnesium, administered ahead of mastectomy, on the development of
      neuropathic pain. As a physiological blocker of NMDAR, magnesium could be an
      interesting candidate to prevent postoperative pain and associated comorbidities,
      including cognitive and emotional disorders, multiple analgesic consumption and
      impaired quality of life. METHODS AND ANALYSIS: A randomised double-blind
      controlled clinical trial (NCT03063931) will include 100 women with breast cancer
      undergoing mastectomy at the Oncology Hospital, Clermont-Ferrand, France.
      Magnesium (100 mg/day; n=50) or placebo (n=50) will be administered for 6 weeks,
      starting 2 weeks before surgery. Intensity of pain, cognitive and emotional
      function and quality of life will be assessed by questionnaires. The primary
      endpoint is pain intensity on a 0-10 numerical rating scale at 1 month
      postmastectomy. Data analysis will use mixed models; all tests will be two
      tailed, with type-I error set at alpha=0.05. ETHICS AND DISSEMINATION: The study
      protocol and informed consent form were approved in December 2016 by the French
      Research Ethics Committee (South East VI Committee). Results will be communicated
      in various congresses and published in international publications. TRIAL
      REGISTRATION NUMBER: NCT03063931.

PMID- 30287602
TI  - Protocol for a prospective multicentre registry cohort study on suicide
      attempters given the assertive case management intervention after admission to an
      emergency department in Japan: post-ACTION-J Study (PACS).
AB  - INTRODUCTION: Suicide attempt is the most important risk factor for later
      suicide. A randomised-controlled, multicentre trial of postsuicide attempt case
      management for the prevention of further suicide attempts in Japan, named ACTION
      J, has established effective interventions for prevention of suicide reattempts.
      The ACTION-J assertive case management intervention programme was adopted by the
      Japanese Ministry of Health, Labour and Welfare in 2016, when medical fees were
      revised. This nationwide programme is provided to patients who attempt suicide
      and who are admitted to emergency departments in Japan.The aim of the present
      study is to examine the current implementation status of the ACTION-J programme.
      The present study also aims to clarify which patients' and hospitals' factors
      affect the implementation of the programme. METHODS AND ANALYSIS: This is a
      prospective, multicentre, patient registry cohort study. Participants will be
      suicide attempters admitted to the emergency departments of medical facilities
      with both psychiatry and emergency departments. The assertive case management
      programme will be delivered to participants by a case manager for up to 24 weeks,
      based on psychiatric diagnoses, social risks and patient needs. The core feature
      of the programme is to encourage patients to participate in psychiatric
      treatment.The primary outcome will be the proportion of patients still
      participating in the case management intervention at 24 weeks after registration.
      The secondary outcomes will include measures of the fidelity of the case
      management intervention. The fidelity will be evaluated using a fidelity
      assessment manual developed by the study group. ETHICS AND DISSEMINATION: This
      observational study has been approved by the ethics board of Sapporo Medical
      University. Enrolment began in October 2016 and will continue until December
      2018. Dissemination plans include presentations at scientific conferences and
      scientific publications. TRIAL REGISTRATION: UMIN000024474.

PMID- 30287601
TI  - Enhancing Social Interaction in Depression (SIDE study): protocol of a randomised
      controlled trial on the effects of a Cognitively Based Compassion Training (CBCT)
      for couples.
AB  - INTRODUCTION: Positive social interactions (PSIs) and stable relationships can
      exert substantial benefits on health. However, patients suffering from depression
      benefit less from these health-promoting effects. Moreover, relationship quality
      and even partners' health has been found to be negatively affected by depressive
      symptomatology, which may result in overall impairments in social functioning of
      a romantic couple. Psychobiological research indicates that these impairments may
      be accompanied by a maladaptive regulation of the patient's neuroendocrine
      response to external stressors. Concerning the improvement of social functioning,
      first studies showed promising results of "Cognitively Based Compassion Training
      (CBCT(r))". However, randomised trials are still scarce. Previous programmes did
      not involve participation of the patient's romantic partner. Therefore, the
      present study aims to investigate whether a CBCT(r) programme adapted for couples
      (CBCT(r)-fC) can improve depressive symptoms, distress, social interaction skills
      and the neurobiological regulation of stress. METHODS AND ANALYSIS: Couples with
      the female partner suffering from depression will be invited to participate in a
      pre-to-post intervention assessment on two consecutive days, respectively,
      involving a standardised PSI task, eye-tracking, ECG recordings, saliva-sampling,
      blood-sampling and questionnaire data. After baseline assessment, participating
      couples will be randomised to either a 10 week CBCT(r)-fC or to a treatment as
      usual control condition. The primary endpoint is the reduction of depressive
      symptoms measured by the Hamilton Depression Rating Scale. Secondary outcomes
      encompass self-rated depression (Beck Depression Inventory), attention towards
      the partners face during PSI (eye tracking), stress-related biomarkers (cortisol,
      alpha-amylase, interleukin (IL)-1beta/IL-6, heart rate variability), methylation
      of oxytocin-receptor-genes and serotonin-transporter-genes and self-ratings of
      psychological constructs such as relationship quality and empathy. ETHICS AND
      DISSEMINATION: Ethical approval has been obtained by the Ethics Committee of the
      Medical Faculty Heidelberg. Results will be presented in international, peer
      reviewed journals and on conferences in the field of clinical psychology and
      psychiatry. TRIAL REGISTRATION NUMBER: NCT03080025.

PMID- 30287603
TI  - Legacy effects of statins on cardiovascular and all-cause mortality: a meta
      analysis.
AB  - OBJECTIVES: To assess evidence for 'legacy' (post-trial) effects on
      cardiovascular disease (CVD) mortality and all-cause mortality among adult
      participants of placebo-controlled randomised controlled trials (RCTs) of
      statins. DESIGN: Meta-analysis of aggregate data. SETTING/PARTICIPANTS: Placebo
      controlled statin RCTS for primary and secondary CVD prevention. METHODS: Data
      sources: PubMed, Embase from inception and forward citations of Cholesterol
      Treatment Trialists' Collaborators RCTs to 16 June 2016. STUDY SELECTION: Two
      independent reviewers identified all statin RCT follow-up reports including
      >=1000 participants, and cardiovascular and all-cause mortality. DATA EXTRACTION
      AND SYNTHESIS: Two independent reviewers extracted data in accordance with the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
      MAIN OUTCOMES: Post-trial CVD and all-cause mortality. RESULTS: We included eight
      trials, with mean post-trial follow-up ranging from 1.6 to 15.1 years, and
      including 13 781 post-trial deaths (6685 CVD). Direct effects of statins within
      trials were greater than legacy effects post-trials. The pooled data from all
      eight studies showed no evidence overall of legacy effects on CVD mortality, but
      some evidence of legacy effects on all-cause mortality (p=0.01). Exploratory
      subgroup analysis found possible differences in legacy effect for primary
      prevention trials compared with secondary prevention trials for both CVD
      mortality (p=0.15) and all-cause mortality (p=0.02). Pooled post-trial HR for the
      three primary prevention studies demonstrated possible post-trial legacy effects
      on CVD mortality (HR=0.87; 95% CI 0.79 to 0.95) and on all-cause mortality
      (HR=0.90; 95% CI 0.85 to 0.96). CONCLUSIONS: Possible post-trial statin legacy
      effects on all-cause mortality appear to be driven by the primary prevention
      studies. Although these relative benefits were smaller than those observed within
      the trial, the absolute benefits may be similar for the two time periods.
      Analysis of individual patient data from follow-up studies after placebo
      controlled statin RCTs in lower-risk populations may provide more definitive
      evidence on whether early treatment of subclinical atherosclerosis is likely to
      be beneficial.

PMID- 30287605
TI  - Ultrasound assessment of diaphragmatic dysfunction as a predictor of weaning
      outcome from mechanical ventilation: a systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this systematic review was to assess the diaphragmatic
      dysfunction (DD) as a predictor of weaning outcome. BACKGROUND: Successful
      weaning depends on several factors: muscle strength, cardiac, respiratory and
      metabolic. Acquired weakness in mechanical ventilation is a growing important
      cause of weaning failure. With the development of ultrasonography, DD can be
      evaluated with ultrasound in weakness patients to predict weaning outcomes.
      METHODS: The Cochrane Library, PubMed, Embase, Ovid Medline, WanFang Data and
      CNKI were systematically searched from the inception to September 2017.
      Ultrasound assessment of DD in adult mechanical ventilation patients was
      included. Two independent investigators assessed study quality in accordance with
      the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcome
      was diaphragmatic thickness and excursion in the weaning success and failure
      group. The secondary outcome was the influence of DD on weaning outcome. RESULTS:
      Eleven studies involving a total of 436 patients were included. There were eight
      studies comparing diaphragmatic excursion (DE), five comparing the diaphragmatic
      thickening fraction (DTF) and two comparing DD between groups with and without
      successful weaning. Overall, the DE or DTF had a pooled sensitivity of 0.85 (95%
      CI 0.77 to 0.91) and a pooled specificity of 0.74 (95% CI 0.66 to 0.80) for
      predicting weaning success. There was high heterogeneity among the included
      studies (I2=80%; p=0.0006). The rate of weaning failure was significantly
      increased in patients with DD (OR 8.82; 95% CI 3.51 to 22.13; p<0.00001).
      CONCLUSIONS: Both DE and DTF showed good diagnostic performance to predict
      weaning outcomes in spite of limitations included high heterogeneity among the
      studies. DD was found to be a predictor of weaning failure in critically ill
      patients.

PMID- 30287606
TI  - Development of a risk predictive scoring system to identify patients at risk of
      representation to emergency department: a retrospective population-based analysis
      in Australia.
AB  - OBJECTIVE: To examine the characteristics of frequent visitors (FVs) to emergency
      departments (EDs) and develop a predictive model to identify those with high risk
      of a future representations to ED among younger and general population (aged <=70
      years). DESIGN AND SETTING: A retrospective analysis of ED data targeting younger
      and general patients (aged <=70 years) were collected between 1 January 2009 and
      30 June 2016 from a public hospital in Australia. PARTICIPANTS: A total of 343
      014 ED presentations were identified from 170 134 individual patients. MAIN
      OUTCOME MEASURES: Proportion of FVs (those attending four or more times
      annually), demographic characteristics (age, sex, indigenous and marital status),
      mode of separation (eg, admitted to ward), triage categories, time of arrival to
      ED, referral on departure and clinical conditions. Statistical estimates using a
      mixed-effects model to develop a risk predictive scoring system. RESULTS: The FVs
      were characterised by young adulthood (32.53%) to late-middle (26.07%) aged
      patients with a higher proportion of indigenous (5.7%) and mental health-related
      presentations (10.92%). They were also more likely to arrive by ambulance
      (36.95%) and leave at own risk without completing their treatments (9.8%). They
      were also highly associated with socially disadvantage groups such as people who
      have been divorced, widowed or separated (12.81%). These findings were then used
      for the development of a predictive model to identify potential FVs. The
      performance of our derived risk predictive model was favourable with an area
      under the receiver operating characteristic (ie, C-statistic) of 65.7%.
      CONCLUSION: The development of a demographic and clinical profile of FVs coupled
      with the use of predictive model can highlight the gaps in interventions and
      identify new opportunities for better health outcome and planning.

PMID- 30287604
TI  - Association of neighbourhood socioeconomic status and diabetes burden using
      electronic health records in Madrid (Spain): the HeartHealthyHoods study.
AB  - OBJECTIVE: To study the association between neighbourhood socioeconomic status
      and diabetes prevalence, incidence, and control in the entire population of
      northeastern Madrid, Spain. SETTING: Electronic health records of the primary
      care system in four districts of Madrid (Spain). PARTICIPANTS: 269 942 people
      aged 40 or older, followed from 2013 to 2014. EXPOSURE:
      Neighbourhoodsocioeconomic status (NSES), measured using a composite index of
      seven indicators from four domains of education, wealth, occupation and living
      conditions. PRIMARY OUTCOME MEASURES: Diagnosis of diabetes based on ICPC-2 codes
      and glycated haemoglobin (HbA1c %). RESULTS: In regression analyses adjusted by
      age and sex and compared with individuals living in low NSES neighbourhoods, men
      living in medium and high NSES neighbourhoods had 10% (95% CI: 6% to 15%) and 29%
      (95% CI: 25% to 32%) lower prevalence of diabetes, while women had 27% (95% CI:
      23% to 30%) and 50% (95% CI: 47% to 52%) lower prevalence of diabetes. Moreover,
      the hazard of diabetes in men living in medium and high NSES neighbourhoods was
      13% (95% CI: 1% to 23%) and 20% (95% CI: 9% to 29%) lower, while the hazard of
      diabetes in women living in medium and high NSES neighbourhoods was 17% (95% CI:
      3% to 29%) and 31% (95% CI: 20% to 41%) lower. Individuals living in medium and
      high SES neighbourhoods had 8% (95% CI: 2% to 15%) and 15% (95% CI: 9% to 21%)
      lower prevalence of lack of diabetes control, and a decrease in average HbA1c %
      of 0.05 (95% CI: 0.01 to 0.10) and 0.11 (95% CI: 0.06 to 0.15). CONCLUSIONS:
      Diabetes prevalence, incidence and lack of control increased with decreasing NSES
      in a southern European city. Future studies should provide mechanistic insights
      and targets for intervention to address this health inequity.

PMID- 30287607
TI  - Prevention of postcontrast acute kidney injury after percutaneous transluminal
      angioplasty by inducing RenalGuard controlled furosemide forced diuresis with
      matched hydration: study protocol for a randomised controlled trial.
AB  - INTRODUCTION: Percutaneous transluminal angioplasty (PTA) is often complicated
      due to postcontrast acute kidney injury (PC-AKI) in patients diagnosed with
      chronic kidney disease (CKD). Hydration therapy is the cornerstone in the
      prevention of PC-AKI. Furosemide forced diuresis with matched hydration using the
      RenalGuard system enables a steady balance between diuresis and hydration. A
      randomised controlled trial will be performed in order to investigate whether
      furosemide forced diuresis with matched hydration in combination with the
      RenalGuard system decreases incidence of PC-AKI in patients with CKD receiving a
      PTA of the lower extremities. Furthermore, we will investigate whether sampling
      of urine biomarkers 4 hours after intervention can detect PC-AKI in an earlier
      stage compared with the golden standard, serum creatinine 48-72 hours
      postintervention. METHODS AND ANALYSIS: A single-centre randomised controlled
      trial will be conducted. Patients >18 years in need of a PTA of the lower
      extremities and diagnosed with CKD will be randomly assigned to receive either
      standard of care prehydration and posthydration or furosemide forced diuresis
      with matched hydration periprocedural using the RenalGuard system. Four hours
      postintervention, a urine sample will be collected of all participating patients.
      Serum creatinine will be sampled within 10 days prior to intervention as well as
      1, 3 and 30 days postintervention. The primary endpoint is incidence of PC-AKI
      post-PTA. Secondary endpoint is the rise of urine biomarkers 4 hours
      postintervention. ETHICS AND DISSEMINATION: Study protocol is approved by the
      research ethics committee and institutional review board (reference number 16 T
      201 and NL59809.096.16). Study results will be disseminated by oral presentation
      at conferences and will be submitted to a peer-reviewed journal. It is
      anticipated that study results will offer a solution to contrast-induced
      nephropathy in patients with CKD receiving a PTA of the lower extremities. TRIAL
      REGISTRATION NUMBER: NTR6236; Pre-results. EUDRACT NUMBER: 2016-005072-10.

PMID- 30287608
TI  - Impact of PCSK9 monoclonal antibodies on circulating hs-CRP levels: a systematic
      review and meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: To evaluate the potential effects of proprotein convertase
      subtilisin/kexin type 9 monoclonal antibody (PCSK9-mAb) on high-sensitivity C
      reactive protein (hs-CRP) concentrations. DESIGN: A systematic review and meta
      analysis of randomised controlled trials. DATA SOURCES: PubMed, MEDLINE, the
      Cochrane Library databases, ClinicalTrials.gov and recent conferences were
      searched from inception to May 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:
      All randomised controlled trials that reported changes of hs-CRP were included.
      RESULTS: Ten studies involving 4198 participants were identified. PCSK9-mAbs
      showed a slight efficacy in reducing hs-CRP (-0.04 mg/L, 95% CI: -0.17 to 0.01)
      which was not statistically different. The results did not altered when subgroup
      analyses were performed including PCSK9-mAb types (alirocumab: 0.12 mg/L, 95% CI:
      -0.18 to 0.43; evolocumab: 0.00 mg/L, 95% CI: -0.07 to 0.07; LY3015014: -0.48
      mg/L, 95% CI: -1.28 to 0.32; RG7652: 0.35 mg/L, 95% CI: -0.26 to 0.96), treatment
      duration (<=12w: 0.00 mg/L, 95% CI: -0.07 to 0.07; >12w: -0.11 mg/L, 95% CI: 
      0.45 to -0.23), participant characteristics (familial hypercholesterolaemia: 0.00
      mg/L, 95% CI: -0.07 to 0.07; non-familial hypercholesterolaemia: 0.07 mg/L, 95%
      CI: -0.12 to 0.26; mix: -0.48 mg/L, 95% CI: -1.28 to 0.32) and treatment methods
      (monotherapy: 0.00 mg/L, -0.08 to 0.07; combination therapy: -0.08 mg/L, -0.37 to
      0.21). Meta-regression analyses suggested no significant linear correlation
      between baseline age (p=0.673), sex (p=0.645) and low-density lipoprotein
      cholesterol reduction (p=0.339). CONCLUSIONS: Our updated meta-analysis suggested
      that PCSK9-mAbs had no significant impact on circulating hs-CRP levels
      irrespective of PCSK9-mAb types, participant characteristics and treatment
      duration or methods.

PMID- 30287609
TI  - Work-related mobility and experiences of gender-based violence among female sex
      workers in Iringa, Tanzania: a cross-sectional analysis of baseline data from
      Project Shikamana.
AB  - OBJECTIVES: To examine how work-related mobility among female sex workers (FSWs)
      is associated with gender-based violence (GBV) in Iringa, Tanzania. DESIGN: Cross
      sectional analyses were conducted on baseline data gathered between October 2015
      and April 2016 from FSWs participating in Project Shikamana, a community
      empowerment-based combination HIV prevention intervention. SETTING: Participants
      were recruited for the baseline study using venue-based time-location sampling in
      two communities in Iringa, Tanzania. PARTICIPANTS: FSWs were eligible for
      participation if they were 18 years or older and had exchanged sex for money
      within the past month. Four-hundred ninety-six FSWs participated in the baseline
      survey. PRIMARY AND SECONDARY OUTCOME MEASURES: Any recent experience of GBV was
      examined by recent work-related mobility among FSWs. Any recent experience of GBV
      was also disaggregated by severity for analyses. All bivariate and multivariate
      binary and multinomial logistic regressions adjusted for intraclass correlations
      among women recruited from the same venues. RESULTS: Forty per cent of
      participants experienced recent physical or sexual violence, and 30% recently
      experienced severe physical or sexual violence. Thirty-three per cent of
      participants recently exchanged sex for money outside of their district or
      region, and 12% were both intraregionally and inter-regionally mobile for sex
      work. Intraregionally and inter-regionally mobile FSWs had 1.9 times greater odds
      of reporting recent GBV (adjusted OR: 1.89; 95% CI: 1.06 to 3.38; p=0.031)
      compared with non-mobile FSWs and a 2.5 times higher relative risk for recent
      experience of severe GBV relative to no recent GBV (relative risk ratio: 2.51;
      95% CI: 1.33 to 4.74; p=0.005). CONCLUSIONS: Mobility for sex work may increase
      FSWs' exposure to GBV, particularly more severe GBV. The vulnerability of mobile
      FSWs to violence, particularly severe forms, demands inclusive services that are
      accessible to mobile FSWs.

PMID- 30287610
TI  - OPtimising Treatment for MIld Systolic hypertension in the Elderly (OPTiMISE):
      protocol for a randomised controlled non-inferiority trial.
AB  - INTRODUCTION: Recent evidence suggests that larger blood pressure reductions and
      multiple antihypertensive drugs may be harmful in older people, particularly
      frail individuals with polypharmacy and multimorbidity. However, there is a lack
      of evidence to support deprescribing of antihypertensives, which limits the
      practice of medication reduction in routine clinical care. The aim of this trial
      is to examine whether antihypertensive medication reduction is possible in older
      patients without significant changes in blood pressure control at follow-up.
      METHODS AND ANALYSIS: This trial will use a primary care-based, open-label,
      randomised controlled trial design. A total of 540 participants will be
      recruited, aged >=80 years, with systolic blood pressure <150 mm Hg and receiving
      >=2 antihypertensive medications. Participants will have no compelling indication
      for medication continuation and will be considered to potentially benefit from
      medication reduction due to existing polypharmacy, comorbidity and frailty.
      Following a baseline appointment, individuals will be randomised to a strategy of
      medication reduction (intervention) with optional self-monitoring or usual care
      (control). Those in the intervention group will have one antihypertensive
      medication stopped. The primary outcome will be to determine if a reduction in
      medication can achieve a proportion of participants with clinically safe blood
      pressure levels at 12-week follow-up (defined as a systolic blood pressure <150
      mm Hg), which is non-inferior (within 10%) to that achieved by the usual care
      group. Qualitative interviews will be used to understand the barriers and
      facilitators to medication reduction. The study will use economic modelling to
      predict the long-term effects of any observed changes in blood pressure and
      quality of life. ETHICS AND DISSEMINATION: The protocol, informed consent form,
      participant information sheet and all other participant facing material have been
      approved by the Research Ethics Committee (South Central-Oxford A; ref
      16/SC/0628), Medicines and Healthcare products Regulatory Agency (ref
      21584/0371/001-0001), host institution(s) and Health Research Authority. All
      research outputs will be published in peer-reviewed journals and presented at
      national and international conferences. TRIAL REGISTRATION NUMBER: EudraCT 2016
      004236-38; ISRCTN97503221; Pre-results.

PMID- 30287611
TI  - Health information technology uses for primary prevention in preventive medicine:
      a scoping review protocol.
AB  - INTRODUCTION: The use of health information technologies (HITs) has been
      associated with positive benefits such as improved health outcomes and improved
      health services. Results from empirical studies reported potential benefits of
      HITs in preventive medicine measures such as primary prevention. This review will
      examine the broad range of HITs and their uses and effectiveness in primary
      prevention. METHODS AND ANALYSIS: We will conduct searches in relevant databases
      (MEDLINE, EMBASE, the Cochrane Methodology Register, Cochrane Database of
      Systematic Reviews, CINAHL, SCOPUS and Web of Science) using Arksey and
      O'Malley's scoping review methodology. The scoping review will include all study
      designs to identify the literature on HIT uses. Two reviewers will independently
      screen the literature following our screening criteria and using a data
      abstraction form. Findings will be summarised quantitatively (using numerical
      counts of HITs) and qualitatively (using narrative synthesis). ETHICS AND
      DISSEMINATION: The study will synthesise data from published literature and will
      not require an ethical approval. The results of the review will be disseminated
      through a peer-reviewed journal.

PMID- 30287612
TI  - Improving sensitivity to eye gaze cues in autism using serious game technology:
      study protocol for a phase I randomised controlled trial.
AB  - INTRODUCTION: Autism spectrum disorder (ASD) is characterised by impairments in
      social communication. Core symptoms are deficits in social looking behaviours,
      including limited visual attention to faces and sensitivity to eye gaze cues. We
      designed an intervention game using serious game mechanics for adolescents with
      ASD. It is designed to train individuals with ASD to discover that the eyes, and
      shifts in gaze specifically, provide information about the external world. We
      predict that the game will increase understanding of gaze cues and attention to
      faces. METHODS AND ANALYSIS: The Social Games for Adolescents with Autism (SAGA)
      trial is a preliminary, randomised controlled trial comparing the intervention
      game with a waitlist control condition. 34 adolescents (10-18 years) with ASD
      with a Full-Scale IQ between 70 and 130 and a minimum second grade reading level,
      and their parents, will be randomly assigned (equally to intervention or the
      control condition) following baseline assessments. Intervention participants will
      be instructed to play the computer game at home on a computer for ~30 min, three
      times a week. All families are tested in the lab at baseline and approximately 2
      months following randomisation in all measures. Primary outcomes are assessed
      with eye tracking to measure sensitivity to eye gaze cues and social visual
      attention to faces; secondary outcomes are assessed with questionnaires to
      measure social skills and autism-like behaviours. The analyses will focus on
      evaluating the feasibility, safety and preliminary effectiveness of the
      intervention. ETHICS AND DISSEMINATION: SAGA is approved by the Institutional
      Review Board at Pennsylvania State University (00005097). Findings will be
      disseminated via scientific conferences and peer-reviewed journals and to
      participants via newsletter. The intervention game will be available to families
      in the control condition after the full data are collected and if analyses
      indicate that it is effective. TRIAL REGISTRATION NUMBER: NCT02968225.

PMID- 30287613
TI  - Plasma concentrations of second-line antituberculosis drugs in relation to
      minimum inhibitory concentrations in multidrug-resistant tuberculosis patients in
      China: a study protocol of a prospective observational cohort study.
AB  - INTRODUCTION: Individualised treatment through therapeutic drug monitoring (TDM)
      may improve tuberculosis (TB) treatment outcomes but is not routinely
      implemented. Prospective clinical studies of drug exposure and minimum inhibitory
      concentrations (MICs) in multidrug-resistant TB (MDR-TB) are scarce. This
      translational study aims to characterise the area under the concentration-time
      curve of individual MDR-TB drugs, divided by the MIC for Mycobacterium
      tuberculosis isolates, to explore associations with markers of treatment progress
      and to develop useful strategies for clinical implementation of TDM in MDR-TB.
      METHODS AND ANALYSIS: Adult patients with pulmonary MDR-TB treated in Xiamen,
      China, are included. Plasma samples for measure of drug exposure are obtained at
      0, 1, 2, 4, 6, 8 and 10 hours after drug intake at week 2 and at 0, 4 and 6 hours
      during weeks 4 and 8. Sputum samples for evaluating time to culture positivity
      and MIC determination are collected at days 0, 2 and 7 and at weeks 2, 4, 8 and
      12 after treatment initiation. Disease severity are assessed with a clinical
      scoring tool (TBscore II) and quality of life evaluated using EQ-5D-5L. Drug
      concentrations of pyrazinamide, ethambutol, levofloxacin, moxifloxacin,
      cycloserine, prothionamide and para-aminosalicylate are measured by liquid
      chromatography tandem-mass spectrometry and the levels of amikacin measured by
      immunoassay. Dried blood spot on filter paper, to facilitate blood sampling for
      analysis of drug concentrations, is also evaluated. The MICs of the drugs listed
      above are determined using custom-made broth microdilution plates and MYCOTB
      plates with Middlebrook 7H9 media. MIC determination of pyrazinamide is performed
      in BACTEC MGIT 960. ETHICS AND DISSEMINATION: This study has been approved by the
      ethical review boards of Karolinska Institutet, Sweden and Fudan University,
      China. Informed written consent is given by participants. The study results will
      be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02816931;
      Pre-results.

PMID- 30287615
TI  - Real-world evidence for postgraduate students and professionals in healthcare:
      protocol for the design of a blended massive open online course.
AB  - INTRODUCTION: There is an increased need for improving data science skills of
      healthcare professionals. Massive open online courses (MOOCs) provide the
      opportunity to train professionals in a sustainable and cost-effective way. We
      present a protocol for the design and development of a blended MOOC on real-world
      evidence (RWE) aimed at improving RWE data science skills. The primary objective
      is to provide the opportunity to understand the fundamentals of RWE data science
      and to implement methods for analysing RWD. The blended format of MOOC will
      combine the expertise of healthcare professionals joining the course online with
      the on-campus students. We expect learners to take skills taught in MOOC and use
      them to seek new employment or to explore entpreneurship activities in these
      domains. METHODS AND ANALYSIS: The proposed MOOC will be developed through a
      blended format using the Analysis, Design, Development, Implementation and
      Evaluation instructional design model and following the connectivist-heutagogical
      learning theories (as a hybrid MOOC). The target learners will include
      postgraduate students and professionals working in the health-related roles with
      interest in data science. An evaluation of MOOC will be performed to assess MOOCs
      success in meeting its intended outcomes and to improve future iterations of the
      course. ETHICS AND DISSEMINATION: The education course design protocol was
      approved by EIT Health (grant 18654) as part of the EIT Health CAMPUS Deferred
      Call for Innovative Education 2018. Results will be published in a peer-reviewed
      journal.

PMID- 30287614
TI  - Caesarean section provision and readiness in Tanzania: analysis of cross
      sectional surveys of women and health facilities over time.
AB  - OBJECTIVES: To describe trends in caesarean sections and facilities performing
      caesareans over time in Tanzania and examine the readiness of such facilities in
      terms of infrastructure, equipment and staffing. DESIGN: Nationally
      representative, repeated cross-sectional surveys of women and health facilities.
      SETTING: Tanzania. PARTICIPANTS: Women of reproductive age and health facility
      staff. MAIN OUTCOME MEASURES: Population-based caesarean rate, absolute annual
      number of caesareans, percentage of facilities reporting to perform caesareans
      and three readiness indicators for safe caesarean care: availability of
      consistent electricity, 24 hour schedule for caesarean and anaesthesia providers,
      and availability of all general anaesthesia equipment. RESULTS: The caesarean
      rate in Tanzania increased threefold from 2% in 1996 to 6% in 2015-16, while the
      total number of births increased by 60%. As a result, the absolute number of
      caesareans increased almost fivefold to 120 000 caesareans per year. The main
      mechanism sustaining the increase in caesareans was the doubling of median
      caesarean volume among public hospitals, from 17 caesareans per month in 2006 to
      35 in 2014-15. The number of facilities performing caesareans increased only
      modestly over the same period. Less than half (43%) of caesareans in Tanzania in
      2014-15 were performed in facilities meeting the three readiness indicators.
      Consistent electricity was widely available, and 24 hour schedules for caesarean
      and (less systematically) anaesthesia providers were observed in most facilities;
      however, the availability of all general anaesthesia equipment was the least
      commonly reported indicator, present in only 44% of all facilities (34% of public
      hospitals). CONCLUSIONS: Given the rising trend in numbers of caesareans, urgent
      improvements in the availability of general anaesthesia equipment and trained
      anaesthesia staff should be made to ensure the safety of caesareans. Initial
      efforts should focus on improving anaesthesia provision in public and faith-based
      organisation hospitals, which together perform more than 90% of all caesareans in
      Tanzania.

PMID- 30287616
TI  - Qualitative protocol for understanding the contribution of Australian policy in
      the urban planning, justice, energy and environment sectors to promoting health
      and health equity.
AB  - INTRODUCTION: A well-established body of literature demonstrates that health and
      equity are strongly influenced by the consequences of governments' policy and
      resultant actions (or inactions) outside the health sector. Consequently, the
      United Nations, and its agency the WHO, have called for national leadership and
      whole-of-government action to understand and address the health impacts of
      policies in all sectors. This research responds to that call by investigating how
      policymaking in four sectors-urban planning, justice, energy and environment-may
      influence the social determinants of health and health equity (SDH/HE). METHODS
      AND ANALYSIS: The research design is informed by a critical qualitative approach.
      Three successive stages are included in the design. The first involves analysing
      all strategic policy documents and selected legislative documents from the four
      sectors (n=583). The document analysis is based on a coding framework developed
      to identify alignment between the documents and the SDH/HE. Two policies that
      demonstrate good practice in regard to SDH/HE will be selected from each sector
      during the second stage for embedded case study analysis (total n=8). This is
      intended to illuminate which factors have supported recognition and action on
      SDH/HE in the selected policies. The third stage involves progressive theoretical
      integration and development to understand political and institutional
      facilitators and barriers to action on SDH/HE, both within and between sectors.
      ETHICS AND DISSEMINATION: The research will provide much needed evidence about
      how coherent whole-of-government action on SDH/HE can be advanced and contribute
      knowledge about how health-enhancing policy activity in the four sectors may be
      optimised. Learnings from the research will be shared via a project advisory
      group, policy briefings, academic papers, conference presentations and research
      symposia. Ethics approval has been secured for the embedded case studies, which
      involve research participants.

PMID- 30287617
TI  - Structural basis of the nucleosome transition during RNA polymerase II passage.
AB  - Genomic DNA forms chromatin, in which the nucleosome is the repeating unit. The
      mechanism by which RNA polymerase II (RNAPII) transcribes the nucleosomal DNA
      remains unclear. Here we report the cryo-electron microscopy structures of RNAPII
      nucleosome complexes in which RNAPII pauses at the superhelical locations SHL(
      6), SHL(-5), SHL(-2), and SHL(-1) of the nucleosome. RNAPII pauses at the major
      histone-DNA contact sites, and the nucleosome interactions with the RNAPII
      subunits stabilize the pause. These structures reveal snapshots of nucleosomal
      transcription, in which RNAPII gradually tears DNA from the histone surface while
      preserving the histone octamer. The nucleosomes in the SHL(-1) complexes are
      bound to a "foreign" DNA segment, which might explain the histone transfer
      mechanism. These results provide the foundations for understanding chromatin
      transcription and epigenetic regulation.

PMID- 30287619
TI  - Reversible self-assembly of superstructured networks.
AB  - Soft structures in nature, such as protein assemblies, can organize reversibly
      into functional and often hierarchical architectures through noncovalent
      interactions. Molecularly encoding this dynamic capability in synthetic materials
      has remained an elusive goal. We report on hydrogels of peptide-DNA conjugates
      and peptides that organize into superstructures of intertwined filaments that
      disassemble upon the addition of molecules or changes in charge density.
      Experiments and simulations demonstrate that this response requires large-scale
      spatial redistribution of molecules directed by strong noncovalent interactions
      among them. Simulations also suggest that the chemically reversible structures
      can only occur within a limited range of supramolecular cohesive energies.
      Storage moduli of the hydrogels change reversibly as superstructures form and
      disappear, as does the phenotype of neural cells in contact with these materials.

PMID- 30287618
TI  - An autoimmune disease variant of IgG1 modulates B cell activation and
      differentiation.
AB  - The maintenance of autoreactive B cells in a quiescent state is crucial for
      preventing autoimmunity. Here we identify a variant of human immunoglobulin G1
      (IgG1) with a Gly396->Arg substitution (hIgG1-G396R), which positively correlates
      with systemic lupus erythematosus. In induced lupus models, murine homolog Gly390
      >Arg (G390R) knockin mice generate excessive numbers of plasma cells, leading to
      a burst of broad-spectrum autoantibodies. This enhanced production of antibodies
      is also observed in hapten-immunized G390R mice, as well as in influenza
      vaccinated human G396R homozygous carriers. This variant potentiates the
      phosphorylation of the IgG1 immunoglobulin tail tyrosine (ITT) motif. This, in
      turn, alters the availability of phospho-ITT to trigger longer adaptor protein
      Grb2 dwell times in immunological synapses, leading to hyper-Grb2-Bruton's
      tyrosine kinase (Btk) signaling upon antigen binding. Thus, the hIgG1-G396R
      variant is important for both lupus pathogenesis and antibody responses after
      vaccination.

PMID- 30287620
TI  - Significant hemolysis is not required for thrombosis in paroxysmal nocturnal
      hemoglobinuria.

PMID- 30287621
TI  - Dyserythropoiesis evaluated by RED score and hepcidin/ferritin levels predicts
      response to erythropoietin in lower risk myelodysplastic syndromes.
AB  - Erythropoiesis-stimulating agents are generally the first line of treatment of
      anemia in lower risk myelodysplastic syndrome patients. We prospectively
      investigated the predictive value of somatic mutations, and biomarkers of
      ineffective erythropoiesis including flow cytometry RED score, serum GDF-15, and
      hepcidin levels. Inclusion criteria were: Erythropoiesis stimulating agents
      naive, IPSS low or intermediate-1 MDS with Hemoglobin level< 10g/dl, red blood
      cell transfusion-dependent or not. Patients received epoetin zeta 40 000 IU/week
      and erythroid response (IWG 2006 criteria) was assessed at week 12. Serum EPO
      level, iron parameters and hepcidin, flow cytometry Ogata and RED score, GDF-15,
      and molecular analysis by next-generation sequencing were determined at baseline.
      70 patients were included. Median age was 78 years. There were 22 RCMD, 19 RCUD,
      14 RARS, 4 RAEB-1, 6 CMML, 2 del 5q-, 3 unclassifiable, IPSS-R was 13 very low,
      47 low, 9 intermediate and high. Twenty patients were transfusion dependent.
      Erythroid response was 48% and median response duration was 26 months. At
      baseline, non-responders had significantly higher RED score, lower
      hepcidin/ferritin ratio. In multivariate analysis, only RED score>4 (p=0.05) and
      hepcidin/ferritin<9 (p=0.02) were significantly associated with worse erythroid
      response. Median response duration was shorter in patients with GDF-15>2000 pg/ml
      and hepcidin/ferritin<9 (P=0.0008, and p=0.01, respectively). In multivariate
      analysis, both variables were associated with shorter response duration.
      Erythroid response to epoetin zeta was similar to that obtained with other
      erythropoiesis stimulating agents. It was correlated with higher baseline
      hepcidin/ferritin ratio and lower RED score.

PMID- 30287622
TI  - Oral ulcer due to dabigatran capsule.

PMID- 30287623
TI  - Bilateral parameatal cysts with associated hypospadias presenting in a newborn
      baby.

PMID- 30287624
TI  - Borderline Mucinous Testicular Tumour: Diagnostic and Management difficulties.
AB  - A 45-year-old man presented with right-sided testicular swelling and pain. An
      examination found a tender, firm right testis, a clinically normal left testis
      and no palpable lymphadenopathy. Tumour and inflammatory markers were within
      normal limits. A scrotal ultrasound scan showed an intratesticular, avascular
      lesion measuring 4.4*2.6*1.8 cm. A CT scan of his chest/abdomen/pelvis (CT C/A/P)
      showed no metastatic or primary lesions. An elective right-inguinal orchidectomy
      was subsequently performed. Histopathology showed a cystic mucinous tumour lined
      with intestinal-type epithelium. Differentials of metastatic adenocarcinoma,
      possibly of a gastrointestinal origin, a monodermal teratoma, or a borderline
      mucinous tumour of the testicle (BMTT) were considered. Following 12 p genetic
      studies and a colonoscopy, both of which found no abnormalities, a presumptive
      diagnosis of a BMTT was made. The patient is to have an annual urological review
      with a CT C/A/P and 5 yearly colonoscopies.

PMID- 30287625
TI  - Sarcoidosis and HIV infection in a native Saudi man.
AB  - Sarcoidosis is a rare condition among native Saudis. It typically presents with
      asymptomatic chest radiographs, exertional breathlessness and cough. The
      coexistence of sarcoidosis and HIV is also rare, and the overlap of the symptoms
      makes their differential diagnosis challenging. Nevertheless, the outcome of
      sarcoidosis is favourable with or without the presence of HIV. We present a case
      of a 55-year-old native Saudi man with extremely atypical sarcoidosis
      presentation coexisting with HIV. This case highlights the association between
      the two pathologies, and the difficulties encountered in establishing a proper
      diagnosis in the presence of two overlapping diseases.

PMID- 30287626
TI  - Cardiac arrest due to critical stenosis of a bicuspid aortic valve mimicking left
      main coronary artery occlusion on ECG.
AB  - A 49-year-old man presented to the emergency room after a cardiac arrest. On
      arrival, the patient's ECG showed ST-segment elevations in the aVR and
      anteroseptal leads with diffuse ST depression suggestive of left main coronary
      artery occlusion. Subsequent coronary catheterisation showed normal coronaries
      but revealed severe stenosis of his bicuspid aortic valve. A surgical replacement
      of the aortic valve was performed, and the patient recovered successfully.

PMID- 30287627
TI  - Hereditary angioedema: a mother diagnosing her child using Google as a diagnostic
      aid.
AB  - Hereditary angioedema (HAE), due to C1-inhibitor deficiency, is a rare autosomal
      dominant and potentially life-threatening disease characterised by recurrent
      oedema attacks of skin, mucosa and viscera. Due to the rarity and the fact that
      symptoms of HAE imitate other forms of angioedema and other conditions, HAE may
      be misdiagnosed, especially in emergency settings. Consequently, patients with
      HAE may experience significant delays in diagnosis. Without an accurate diagnosis
      patients with HAE may not receive proper treatment. At times 'Doctor Google' may
      be an important tool in establishing the diagnosis. The aim of this case report
      is to emphasise the importance of listening to patients and relatives and being
      humble to 'Doctor Google'. Furthermore, the aim is to remind all healthcare
      personal of HAE and the importance of considering the rare differential diagnoses
      to common symptoms.

PMID- 30287629
TI  - Correction: Severe capillary leak syndrome with cardiac arrest triggered by
      influenza virus infection.

PMID- 30287628
TI  - Pericardial effusion as first presentation of disseminated non-Hodgkin's
      lymphoma.
AB  - A 46-year-old woman with quiescent lupus presented with worsening pleuritic chest
      pain and dyspnoea. Bedside echocardiogram confirmed large pericardial effusion
      with cardiac tamponade. Emergency bedside pericardiocentesis was performed.
      Pericardial fluid cytology confirmed diffuse large B cell lymphoma, stage four on
      positron emission tomography. Conventional rituximab, cyclophosphamide,
      doxorubicin, vincristine and prednisolone chemotherapy achieved good response in
      all sites except the pericardium. Progressive cardiac involvement was complicated
      by atrioventricular conduction block requiring permanent pacemaker. Second-line
      palliative chemotherapy was performed.

PMID- 30287630
TI  - Heart of the matter: reverse takotsubo syndrome in an anthracycline-exposed
      oncology patient.
AB  - A 24-year-old man with acute myelogenous leukaemia and a history of anthracycline
      treatment is hospitalised for non-anthracycline chemotherapy. He develops new
      onset heart failure requiring intesive care unit (ICU) admission during his stay.
      There is debate as to the aetiology of his heart failure, whether anthracycline
      cardiotoxicity or takotsubo syndrome. He is diuresed and discharged home with
      close follow-up. Ultimately, the retrospective use of two-dimensional speckle
      tracking echocardiography derived strain helps diagnose reverse takotsubo
      syndrome.

PMID- 30287631
TI  - A radiation belt of energetic protons located between Saturn and its rings.
AB  - Saturn has a sufficiently strong dipole magnetic field to trap high-energy
      charged particles and form radiation belts, which have been observed outside its
      rings. Whether stable radiation belts exist near the planet and inward of the
      rings was previously unknown. The Cassini spacecraft's Magnetosphere Imaging
      Instrument obtained measurements of a radiation belt that lies just above
      Saturn's dense atmosphere and is decoupled from the rest of the magnetosphere by
      the planet's A- to C-rings. The belt extends across the D-ring and comprises
      protons produced through cosmic ray albedo neutron decay and multiple charge
      exchange reactions. These protons are lost to atmospheric neutrals and D-ring
      dust. Strong proton depletions that map onto features on the D-ring indicate a
      highly structured and diverse dust environment near Saturn.

PMID- 30287632
TI  - The low-frequency source of Saturn's kilometric radiation.
AB  - Understanding how auroral radio emissions are produced by magnetized bodies
      requires in situ measurements within their source region. Saturn's kilometric
      radiation (SKR) has been widely used as a remote proxy of Saturn's magnetosphere.
      We present wave and plasma measurements from the Cassini spacecraft during its
      ring-grazing high-inclination orbits, which passed three times through the high
      altitude SKR emission region. Northern dawn-side, narrow-banded radio sources
      were encountered at frequencies of 10 to 20 kilohertz, within regions of upward
      currents mapping to the ultraviolet auroral oval. The kilometric waves were
      produced on the extraordinary mode by the cyclotron maser instability from 6- to
      12-kilo-electron volt electron beams and radiated quasi-perpendicularly to the
      auroral magnetic field lines. The SKR low-frequency sources appear to be strongly
      controlled by time-variable magnetospheric electron densities.

PMID- 30287633
TI  - Dust grains fall from Saturn's D-ring into its equatorial upper atmosphere.
AB  - The sizes of Saturn's ring particles range from meters (boulders) to nanometers
      (dust). Determination of the rings' ages depends on loss processes, including the
      transport of dust into Saturn's atmosphere. During the Grand Finale orbits of the
      Cassini spacecraft, its instruments measured tiny dust grains that compose the
      innermost D-ring of Saturn. The nanometer-sized dust experiences collisions with
      exospheric (upper atmosphere) hydrogen and molecular hydrogen, which forces it to
      fall from the ring into the ionosphere and lower atmosphere. We used the
      Magnetospheric Imaging Instrument to detect and characterize this dust transport
      and also found that diffusion dominates above and near the altitude of peak
      ionospheric density. This mechanism results in a mass deposition into the
      equatorial atmosphere of ~5 kilograms per second, constraining the age of the D
      ring.

PMID- 30287634
TI  - Chemical interactions between Saturn's atmosphere and its rings.
AB  - The Pioneer and Voyager spacecraft made close-up measurements of Saturn's
      ionosphere and upper atmosphere in the 1970s and 1980s that suggested a chemical
      interaction between the rings and atmosphere. Exploring this interaction provides
      information on ring composition and the influence on Saturn's atmosphere from
      infalling material. The Cassini Ion Neutral Mass Spectrometer sampled in situ the
      region between the D ring and Saturn during the spacecraft's Grand Finale phase.
      We used these measurements to characterize the atmospheric structure and material
      influx from the rings. The atmospheric He/H2 ratio is 10 to 16%. Volatile
      compounds from the rings (methane; carbon monoxide and/or molecular nitrogen), as
      well as larger organic-bearing grains, are flowing inward at a rate of 4800 to
      45,000 kilograms per second.

PMID- 30287635
TI  - In situ collection of dust grains falling from Saturn's rings into its
      atmosphere.
AB  - Saturn's main rings are composed of >95% water ice, and the nature of the
      remaining few percent has remained unclear. The Cassini spacecraft's traversals
      between Saturn and its innermost D ring allowed its cosmic dust analyzer (CDA) to
      collect material released from the main rings and to characterize the ring
      material infall into Saturn. We report the direct in situ detection of material
      from Saturn's dense rings by the CDA impact mass spectrometer. Most detected
      grains are a few tens of nanometers in size and dynamically associated with the
      previously inferred "ring rain." Silicate and water-ice grains were identified,
      in proportions that vary with latitude. Silicate grains constitute up to 30% of
      infalling grains, a higher percentage than the bulk silicate content of the
      rings.

PMID- 30287637
TI  - Renewable energy for Puerto Rico.

PMID- 30287636
TI  - Saturn's magnetic field revealed by the Cassini Grand Finale.
AB  - During 2017, the Cassini fluxgate magnetometer made in situ measurements of
      Saturn's magnetic field at distances ~2550 +/- 1290 kilometers above the 1-bar
      surface during 22 highly inclined Grand Finale orbits. These observations refine
      the extreme axisymmetry of Saturn's internal magnetic field and show displacement
      of the magnetic equator northward from the planet's physical equator. Persistent
      small-scale magnetic structures, corresponding to high-degree (>3) axisymmetric
      magnetic moments, were observed. This suggests secondary shallow dynamo action in
      the semiconducting region of Saturn's interior. Some high-degree magnetic moments
      could arise from strong high-latitude concentrations of magnetic flux within the
      planet's deep dynamo. A strong field-aligned current (FAC) system is located
      between Saturn and the inner edge of its D-ring, with strength comparable to the
      high-latitude auroral FACs.

PMID- 30287638
TI  - News at a glance.

PMID- 30287639
TI  - BepiColombo set to probe Mercury's mysteries.

PMID- 30287640
TI  - Trio earns physics Nobel for turning lasers into tools.

PMID- 30287641
TI  - Cancer immunotherapy sweeps Nobel for medicine.

PMID- 30287643
TI  - Airlines fight effort to force them to carry lab animals.

PMID- 30287642
TI  - New science minister's activism sparks debate.

PMID- 30287644
TI  - Sky rivers.

PMID- 30287646
TI  - Marsupial responses to global aridification.

PMID- 30287645
TI  - NextGen Voices: Quality mentoring.

PMID- 30287647
TI  - Smoothening out the patches.

PMID- 30287648
TI  - Activating plasmonic chemistry.

PMID- 30287649
TI  - Metropolitan versus small-town influenza.

PMID- 30287650
TI  - Cancer origins-genetics rules the day.

PMID- 30287651
TI  - Quantum oscillations in an insulator.

PMID- 30287652
TI  - Preserving microbial diversity.

PMID- 30287653
TI  - Agricultural research, or a new bioweapon system?

PMID- 30287654
TI  - Diving within Saturn's rings.

PMID- 30287655
TI  - Glacial lake outburst floods as drivers of fluvial erosion in the Himalaya.
AB  - Himalayan rivers are frequently hit by catastrophic floods that are caused by the
      failure of glacial lake and landslide dams; however, the dynamics and long-term
      impacts of such floods remain poorly understood. We present a comprehensive set
      of observations that capture the July 2016 glacial lake outburst flood (GLOF) in
      the Bhotekoshi/Sunkoshi River of Nepal. Seismic records of the flood provide new
      insights into GLOF mechanics and their ability to mobilize large boulders that
      otherwise prevent channel erosion. Because of this boulder mobilization, GLOF
      impacts far exceed those of the annual summer monsoon, and GLOFs may dominate
      fluvial erosion and channel-hillslope coupling many tens of kilometers downstream
      of glaciated areas. Long-term valley evolution in these regions may therefore be
      driven by GLOF frequency and magnitude, rather than by precipitation.

PMID- 30287656
TI  - Rapid change of superconductivity and electron-phonon coupling through critical
      doping in Bi-2212.
AB  - Electron-boson coupling plays a key role in superconductivity for many systems.
      However, in copper-based high-critical temperature (T c) superconductors, its
      relation to superconductivity remains controversial despite strong spectroscopic
      fingerprints. In this study, we used angle-resolved photoemission spectroscopy to
      find a pronounced correlation between the superconducting gap and the bosonic
      coupling strength near the Brillouin zone boundary in Bi2Sr2CaCu2O8+delta The
      bosonic coupling strength rapidly increases from the overdoped Fermi liquid
      regime to the optimally doped strange metal, concomitant with the quadrupled
      superconducting gap and the doubled gap-to-T c ratio across the pseudogap
      boundary. This synchronized lattice and electronic response suggests that the
      effects of electronic interaction and the electron-phonon coupling (EPC)
      reinforce each other in a positive-feedback loop upon entering the strange-metal
      regime, which in turn drives a stronger superconductivity.

PMID- 30287657
TI  - Quantifying hot carrier and thermal contributions in plasmonic photocatalysis.
AB  - Photocatalysis based on optically active, "plasmonic" metal nanoparticles has
      emerged as a promising approach to facilitate light-driven chemical conversions
      under far milder conditions than thermal catalysis. However, an understanding of
      the relation between thermal and electronic excitations has been lacking. We
      report the substantial light-induced reduction of the thermal activation barrier
      for ammonia decomposition on a plasmonic photocatalyst. We introduce the concept
      of a light-dependent activation barrier to account for the effect of light
      illumination on electronic and thermal excitations in a single unified picture.
      This framework provides insight into the specific role of hot carriers in plasmon
      mediated photochemistry, which is critically important for designing energy
      efficient plasmonic photocatalysts.

PMID- 30287658
TI  - Rapid Pliocene adaptive radiation of modern kangaroos.
AB  - Differentiating between ancient and younger, more rapidly evolved clades is
      important for determining paleoenvironmental drivers of diversification.
      Australia possesses many aridity-adapted lineages, the origins of which have been
      closely linked to late Miocene continental aridification. Using dental macrowear
      and molar crown height measurements, spanning the past 25 million years, we show
      that the most iconic Australian terrestrial mammals, "true" kangaroos
      (Macropodini), adaptively radiated in response to mid-Pliocene grassland
      expansion rather than Miocene aridity. In contrast, low-crowned, short-faced
      kangaroos radiated into predominantly browsing niches as the late Cenozoic became
      more arid, contradicting the view that this was an interval of global browser
      decline. Our results implicate warm-to-cool climatic oscillations as a trigger
      for adaptive radiation and refute arguments attributing Pleistocene megafaunal
      extinction to aridity-forced dietary change.

PMID- 30287659
TI  - Urbanization and humidity shape the intensity of influenza epidemics in U.S.
      cities.
AB  - Influenza epidemics vary in intensity from year to year, driven by climatic
      conditions and by viral antigenic evolution. However, important spatial variation
      remains unexplained. Here we show predictable differences in influenza incidence
      among cities, driven by population size and structure. Weekly incidence data from
      603 cities in the United States reveal that epidemics in smaller cities are
      focused on shorter periods of the influenza season, whereas in larger cities,
      incidence is more diffuse. Base transmission potential estimated from city-level
      incidence data is positively correlated with population size and with
      spatiotemporal organization in population density, indicating a milder response
      to climate forcing in metropolises. This suggests that urban centers incubate
      critical chains of transmission outside of peak climatic conditions, altering the
      spatiotemporal geometry of herd immunity.

PMID- 30287661
TI  - The role of education interventions in improving economic rationality.
AB  - Schooling rewards people with labor market returns and nonpecuniary benefits in
      other realms of life. However, there is no experimental evidence showing that
      education interventions improve individual economic rationality. We examine this
      hypothesis by studying a randomized 1-year financial support program for
      education in Malawi that reduced absence and dropout rates and increased scores
      on a qualification exam of female secondary school students. We measure economic
      rationality 4 years after the intervention by using lab-in-the-field experiments
      to create scores of consistency with utility maximization that are derived from
      revealed preference theory. We find that students assigned to the intervention
      had higher scores of rationality. The results remain robust after controlling for
      changes in cognitive and noncognitive skills. Our results suggest that education
      enhances the quality of economic decision-making.

PMID- 30287663
TI  - More than my publications.

PMID- 30287662
TI  - Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine
      cancer lineage.
AB  - The use of potent therapies inhibiting critical oncogenic pathways active in
      epithelial cancers has led to multiple resistance mechanisms, including the
      development of highly aggressive, small cell neuroendocrine carcinoma (SCNC).
      SCNC patients have a dismal prognosis due in part to a limited understanding of
      the molecular mechanisms driving this malignancy and the lack of effective
      treatments. Here, we demonstrate that a common set of defined oncogenic drivers
      reproducibly reprograms normal human prostate and lung epithelial cells to small
      cell prostate cancer (SCPC) and small cell lung cancer (SCLC), respectively. We
      identify shared active transcription factor binding regions in the reprogrammed
      prostate and lung SCNCs by integrative analyses of epigenetic and transcriptional
      landscapes. These results suggest that neuroendocrine cancers arising from
      distinct epithelial tissues may share common vulnerabilities that could be
      exploited for the development of drugs targeting SCNCs.

PMID- 30287660
TI  - Impacts of species richness on productivity in a large-scale subtropical forest
      experiment.
AB  - Biodiversity experiments have shown that species loss reduces ecosystem
      functioning in grassland. To test whether this result can be extrapolated to
      forests, the main contributors to terrestrial primary productivity, requires
      large-scale experiments. We manipulated tree species richness by planting more
      than 150,000 trees in plots with 1 to 16 species. Simulating multiple extinction
      scenarios, we found that richness strongly increased stand-level productivity.
      After 8 years, 16-species mixtures had accumulated over twice the amount of
      carbon found in average monocultures and similar amounts as those of two
      commercial monocultures. Species richness effects were strongly associated with
      functional and phylogenetic diversity. A shrub addition treatment reduced tree
      productivity, but this reduction was smaller at high shrub species richness. Our
      results encourage multispecies afforestation strategies to restore biodiversity
      and mitigate climate change.

PMID- 30287664
TI  - Impact of workplace violence and compassionate behaviour in hospitals on stress,
      sleep quality and subjective health status among Chinese nurses: a cross
      sectional survey.
AB  - OBJECTIVES: The aim of this study is to describe the current state of workplace
      violence (WPV) and compassionate behaviour towards nurses and to explain how they
      affect nurses' stress, sleep quality and subjective health status. DESIGN: A
      cross-sectional online survey study. SETTING: The survey was conducted across
      eight provinces in China. PARTICIPANTS: A total of 1024 nurses were recruited to
      complete an online questionnaire survey from February to May 2016 in China.
      RESULTS: Approximately 75.4% participants had experienced some form of violence.
      Most of the participants experienced WPV such as verbal violence (65.2%), made
      difficulties (54.5%), tarnished reputation (37.5%), mob behaviour (34.9%),
      intimidation behaviour (18.8%), physical violence (14.6%) and sexual harassment
      (5.9%). In this study, 92.4% participants experienced compassionate behaviour
      from their coworkers (84.9%), supervisors (67.3%), and from their patients
      (65.3%). The results show that the exposure to WPV behaviour significantly
      affected the psychological stress (beta=0.295, p<0.01), sleep quality (beta=
      0.198, p<0.01) and subjective health status (beta=-0.252, p<0.01) of nurses. The
      exposure to compassionate behaviour significantly affected the psychological
      stress (beta=-0.229, p<0.01), sleep quality (beta=0.326, p<0.01) and subjective
      health status (beta=0.342, p<0.01) of nurses. The results of the mediation
      analysis showed that psychological stress is a partial mediator in the
      relationship between violence and sleep quality (beta=-0.458, p<0.01) and between
      violence and subjective health (beta=-0.425, p<0.01). Moreover, psychological
      stress also partially mediated the relationship between compassionate behaviour
      and sleep quality (beta=-0.473, p<0.01), and between compassionate behaviour and
      subjective health (beta=-0.405, p<0.01). CONCLUSION: In China, most nurses have
      experienced different forms of WPV from patients and/or their relatives, as well
      as experiencing various forms of compassionate behaviour from their coworkers,
      supervisors and/or patients. This study investigates the prevalence of the
      different types of WPV and compassionate behaviour. Several aspects of harm to
      nurses from exposure to violence is confirmed. We found that WPV can damage
      nurses' health outcomes, while compassionate behaviours were beneficial to their
      health outcomes. A harmonious nursing environment should be provided to minimise
      threats to nurses' health status.

PMID- 30287665
TI  - Practice of informed consent in Guangdong, China: a qualitative study from the
      perspective of in-hospital patients.
AB  - OBJECTIVE: This study aimed to investigate the practice of informed consent in
      China from the perspective of patients. DESIGN: A qualitative study using in
      depth interviews with in-hospital patients focusing on personal experience with
      informed consent. SETTING: Guangdong Province, China. PARTICIPANTS: 71 in
      hospital patients in rehabilitation after surgical operations were included.
      RESULTS: Medical information is not actively conveyed by doctors nor effectively
      received by patients. Without complete and understandable information, patients
      are unable to make an autonomous clinical decision but must sign an informed
      consent form following the doctor's medical arrangement. Three barriers to
      accessing medical information by patients were identified: (1) medical
      information received by patients was insufficient to support their decision
      making, (2) patients lacked medical knowledge to understand the perceptions of
      doctors and (3) patient-doctor interactions were insufficient in clinical
      settings. CONCLUSIONS: Informed consent is implemented as an administrative
      procedure at the hospital level in China. However, it has not been embedded in
      doctors' clinical practices because, from the perspective of patients, doctors do
      not fulfil the obligation of medical information provision. As a result, the
      informed part of informed consent was neglected by individual doctors in China.
      Reforming medical education, monitoring the process of informed consent in
      clinical settings and redesigning medical institutional arrangements are pathways
      to restoring the practice of informed consent and patient-centred models in
      China.

PMID- 30287666
TI  - Socioeconomic position, symptoms of depression and subsequent mental healthcare
      treatment: a Danish register-based 6-month follow-up study on a population
      survey.
AB  - OBJECTIVE: Examine whether the severity of symptoms of depression was associated
      with the type of mental healthcare treatment (MHCT) received, independent of
      socioeconomic position (SEP). DESIGN: Register-based 6-month follow-up study on
      participants from the Danish General Suburban Population Study (GESUS) 2010-2013,
      who scored the Major Depression Inventory (MDI). PARTICIPANTS: Nineteen thousand
      and eleven respondents from GESUS. INTERVENTIONS: The MHCT of the participants
      was tracked in national registers 4 months prior and 6 months after their MDI
      scores. MHCT was graduated in levels. SEP was defined by years of formal
      postsecondary education and income categorised into three levels. Data were
      analysed using logistic and Poisson regression analyses. OUTCOMES: MHCT included
      number of contacts with: general practitioner (GP), GP mental health counselling,
      psychologist, psychiatrist, emergency contacts, admissions to psychiatric
      hospitals and prescriptions of antidepressants. RESULTS: For 547 respondents with
      moderate to severe symptoms of depression there was no difference across SEP in
      use of services, contact (y/n), frequency of contact or level of treatment,
      except respondents with low SEP had more frequent contact with their GP. However,
      of the 547 respondents , 10% had no treatment contacts at all, and 47% had no
      treatment beyond GP consultation. Among respondents with no/few symptoms of
      depression, postsecondary education >=3 years was associated with more contact
      with specialised services (adjusted OR (aOR) 1.92; 95% CI 1.18 to 3.13); however,
      this difference did not apply for income; additionally, high SEP was associated
      with fewer prescriptions of antidepressants (education aOR 0.69; CI 0.50 to 0.95;
      income aOR 0.56, CI 0.39 to 0.80) compared with low SEP. CONCLUSION: Participants
      with symptoms of depression were treated according to the severity of their
      symptoms, independent of SEP; however, more than half with moderate to severe
      symptoms received no treatment beyond GP consultation. People in low SEP and
      no/few symptoms of depression were more often treated with antidepressants. The
      study was approved by The Danish Data Protection Agency Journal number 2015-41
      3984. Accessible at: https://www.datatilsynet.dk/fortegnelsen/soeg-i
      fortegnelsen/.

PMID- 30287667
TI  - Effect of national HIV testing recommendations and local interventions on HIV
      testing practices in a Swiss university hospital: a retrospective analysis
      between 2012 and 2015.
AB  - OBJECTIVES: Despite HIV testing recommendations published by the Federal Office
      of Public Health (FOPH) since 2007, many individuals living with HIV are
      diagnosed late in Switzerland. The aim of this study is to examine the effect of
      the 2013 FOPH HIV testing recommendations on HIV testing rates. SETTING: Ten
      clinical services at Lausanne University Hospital, Lausanne, Switzerland.
      PARTICIPANTS: Patients attending between 1 January 2012 and 31 December 2015.
      DESIGN: Retrospective analysis using two existing hospital databases. HIV testing
      rates calculated as the percentage of tests performed (from the Immunology
      Service database) per number of patients seen (from the central hospital
      database). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was
      testing rate change following the 2013 FOPH testing recommendations, comparing
      testing rates 2 years before and 2 years after their publication. Secondary
      outcomes were demographic factors of patients tested or not tested for HIV.
      RESULTS: 147 884 patients were seen during the study period of whom 9653 (6.5%)
      were tested for HIV, with 34 new HIV diagnoses. Mean testing rate increased from
      5.6% to 7.8% after the recommendations (p=0.001). Testing rate increases were
      most marked in services involved in clinical trials on HIV testing, whose staff
      had attended training seminars on testing indications and practice. Testing rates
      were lower among older (aged >50 years), female and Swiss patients compared with
      younger, male and non-Swiss patients, both globally (p=0.001) and in specific
      clinical services. CONCLUSIONS: This simple two-database tool demonstrates
      clinical services in which HIV testing practice can be optimised. Improved
      testing rates in services involved in clinical trials on testing suggest that
      local engagement complements the effect of national recommendations. While,
      overall, HIV testing rates increased significantly over time, testing rates were
      lower among patients with similar demographic profiles to individuals diagnosed
      late in Switzerland.

PMID- 30287668
TI  - Smoking as a risk factor for lung cancer in women and men: a systematic review
      and meta-analysis.
AB  - OBJECTIVES: To investigate the sex-specific association between smoking and lung
      cancer. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched
      PubMed and EMBASE from 1 January 1999 to 15 April 2016 for cohort studies. Cohort
      studies before 1 January 1999 were retrieved from a previous meta-analysis.
      Individual participant data from three sources were also available to supplement
      analyses of published literature. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:
      Cohort studies reporting the sex-specific relative risk (RR) of lung cancer
      associated with smoking. RESULTS: Data from 29 studies representing 99 cohort
      studies, 7 million individuals and >50 000 incident lung cancer cases were
      included. The sex-specific RRs and their ratio comparing women with men were
      pooled using random-effects meta-analysis with inverse-variance weighting. The
      pooled multiple-adjusted lung cancer RR was 6.99 (95% Confidence Interval (CI)
      5.09 to 9.59) in women and 7.33 (95% CI 4.90 to 10.96) in men. The pooled ratio
      of the RRs was 0.92 (95% CI 0.72 to 1.16; I2=89%; p<0.001), with no evidence of
      publication bias or differences across major pre-defined participant and study
      subtypes. The women-to-men ratio of RRs was 0.99 (95% CI 0.65 to 1.52), 1.11 (95%
      CI 0.75 to 1.64) and 0.94 (95% CI 0.69 to 1.30), for light, moderate and heavy
      smoking, respectively. CONCLUSIONS: Smoking yields similar risks of lung cancer
      in women compared with men. However, these data may underestimate the true risks
      of lung cancer among women, as the smoking epidemic has not yet reached full
      maturity in women. Continued efforts to measure the sex-specific association of
      smoking and lung cancer are required.

PMID- 30287669
TI  - Acceptance and Commitment Therapy for Muscle Disease (ACTMus): protocol for a two
      arm randomised controlled trial of a brief guided self-help ACT programme for
      improving quality of life in people with muscle diseases.
AB  - INTRODUCTION: In adults, muscle disease (MD) is often a chronic long-term
      condition with no definitive cure. It causes wasting and weakness of the muscles
      resulting in a progressive decline in mobility, alongside other symptoms, and is
      typically associated with reduced quality of life (QoL). Previous research
      suggests that a psychological intervention, and in particular Acceptance and
      Commitment Therapy (ACT), may help improve QoL in MD. ACT is a newer type of
      cognitive behavioural treatment that aims to improve QoL by virtue of improvement
      in a process called psychological flexibility. The primary aim of this randomised
      controlled trial (RCT) is to evaluate the efficacy of a guided self-help ACT
      programme for improving QoL in people with MD. Main secondary outcomes are mood,
      symptom impact, work and social adjustment and function at 9-week follow-up.
      METHODS AND ANALYSIS: Acceptance and Commitment Therapy for Muscle Disease is an
      assessor-blind, multicentre, two-armed, parallel-group RCT to assess the efficacy
      of ACT plus standard medical care (SMC) compared with SMC alone. Individuals with
      a diagnosis of one of four specific MDs, with a duration of at least 6 months and
      with mild to moderate anxiety or depression (Hospital Anxiety and Depression
      Scale score >=8) will be recruited from UK-based MD clinics and MD patient
      support organisations. Participants will be randomised to either ACT plus SMC or
      SMC alone by an independent randomisation service. Participants will be followed
      up at 3, 6 and 9 weeks. Analysis will be intention to treat, conducted by the
      trial statistician who will be blinded to treatment allocation. ETHICS AND
      DISSEMINATION: The study has received full ethical approval. Study results will
      be disseminated via peer-reviewed publications, conference presentations and
      journal articles. Data obtained from the trial will enable clinicians and health
      service providers to make informed decisions regarding the efficacy of ACT for
      improving QoL for patients with MD. TRIAL REGISTRATION NUMBER: NCT02810028.
      PROTOCOL VERSION: V.11 (4 April 2017).

PMID- 30287670
TI  - Research protocol for the exploration of experiences of Aboriginal Australian
      mothers and healthcare professionals when using the Edinburgh Postnatal
      Depression Scale: a process-oriented validation study using triangulated
      participatory mixed methods.
AB  - INTRODUCTION: Adopting a process-oriented framework for test validation can help
      to establish whether this tool has the potential to be an acceptable, valid and
      reliable indicator of depression for mothers and mothers-to-be. This mixed
      methods research protocol seeks to explore the views and experiences of
      Aboriginal mothers and healthcare professionals in relation to the Edinburgh
      Postnatal Depression Scale (EPDS), and is intended to highlight potential
      barriers in perinatal mental health conceptualisation, engagement and response
      style. METHODS AND ANALYSIS: Thematic analysis will be applied to interview
      transcripts of Aboriginal Australian mothers (n=6+) and healthcare professionals
      (n=6+) to identify key themes. The process-focused validation model will use
      narratives about experiences of using the EPDS as the priority point of analysis.
      Item-level data and process-level (experience) data are key phenomenological
      data. The interview-based narratives will be then compared with EPDS scores to
      check for points of congruence and divergence. This will be done at two time
      points, antenatally and postnatally, to assess changes in assessment processes
      and perceptions. Bridging evidence-based research with clinical practice in an
      Aboriginal Australian context will be facilitated by an investigation of the
      perceived cultural relevance and likely clinical effectiveness of EPDS. Such
      evidence is critical to understanding whether the EPDS fulfils its intended
      purpose. The guiding principles in designing this research protocol is to benefit
      the well-being of young Aboriginal families and communities through partnership
      with Aboriginal women. ETHICS AND DISSEMINATION: Ethics approval was obtained
      from Human Research Ethics Committee of Murdoch University and from Western
      Australian Aboriginal Health Ethics Committee (WAAHEC). Participating healthcare
      sites and services have provided letters of support. Results of this study will
      be submitted for publication in a peer-reviewed journal.

PMID- 30287671
TI  - Glimepiride monotherapy versus combination of glimepiride and linagliptin therapy
      in patients with HNF1A-diabetes: a protocol for a randomised, double-blinded,
      placebo-controlled trial.
AB  - INTRODUCTION: Hepatocyte nuclear factor 1alpha (HNF1A)-diabetes is the most
      common monogenetic subtype of diabetes. Strict glycaemic control is crucial for a
      good prognosis for patients with HNF1A-diabetes. Sulfonylurea (SU) is used as a
      first-line therapy in HNF1A-diabetes. However, SU therapy may be problematic as
      it confers a high risk of hypoglycaemia. We hypothesise that low dose of SU in
      combination with a dipeptidyl peptidase 4 inhibitor provides a safer and more
      efficacious treatment in patients with HNF1A-diabetes compared with SU as
      monotherapy. METHODS AND ANALYSIS: In a randomised, double-blinded, crossover
      study, patients with HNF1A-diabetes will randomly be assigned to 16 weeks of
      treatment with glimepiride+linagliptin, 4 weeks of washout and 16 weeks of
      treatment with glimepiride+placebo (or vice versa). Treatment will be evaluated
      with continuous glucose monitoring and combined meal and bicycle tests conducted
      at baseline and at the end of each of the two treatment periods. The primary end
      point is the absolute difference in the mean amplitude of glycaemic excursions
      between the two treatments (glimepiride+linagliptin vs glimepiride+placebo) at
      the end of each treatment period. ETHICS AND DISSEMINATION: The study protocol is
      approved by the Danish Medicines Agency, The Scientific-Ethical Committee of the
      Capital Region of Denmark (H-17014518) and the Danish Data Protection Agency. The
      trial will be carried out and monitored in compliance with Good Clinical Practice
      guidelines and in accordance with the latest version of the Declaration of
      Helsinki. Positive, negative and inconclusive results will be published at
      scientific conferences and as one or more scientific manuscripts in peer-reviewed
      journals with authorship in accordance with the International Committee of
      Medical Journal Editors' recommendations. TRIAL REGISTRATION NUMBER: 2017-000204
      15.

PMID- 30287672
TI  - Twenty-year time trends in hypertension prevalence in Yi people of China: three
      successive cross-sectional studies, 1996-2015.
AB  - OBJECTIVE: To explore the trend of hypertension prevalence and related factors in
      Yi people from 1996 to 2015. METHODS: Three successive cross-sectional surveys
      were conducted in Liangshan Yi Autonomous Prefecture in 1996, 2007 and 2015,
      respectively. A total of 8448 participants aged 20-80 years (5040 Yi farmers,
      3408 Yi migrants) were included in final analysis. RESULTS: Overall, the age
      standardised prevalence of hypertension in migrants was significantly higher than
      in farmers. Furthermore, the age-standardised prevalence rates increased from
      10.1% to 15.3% to 19.6% in Yi migrants and from 4.0% to 6.3% to 13.1% in Yi
      farmers during 1996 to 2007 to 2015. The highest 2015-to-1996 ratio of age
      standardised hypertension prevalence was in male farmers (ratio=4.30), whereas
      despite the highest prevalence of hypertension, the equivalent figure in male
      migrants was 1.57. The older age, overweight and obesity were persistent risk
      factors of hypertension in three periods. After adjusted for age and body mass
      index, the difference of hypertension prevalence between 1996 and 2015 then
      vanished in male migrants (OR=1.335; 95% CI: 0.884 to 2.015) and female farmers
      (OR=1.267; 95% CI: 0.590 to 2.719). The disparities of hypertension prevalence
      between Yi migrants and farmers were not statistically significant in all
      subgroups when adjusted for age, body mass index and education. CONCLUSIONS: Over
      the past two decades, the hypertension prevalence in Yi people has significantly
      increased. Yi migrants were more likely to be hypertensive than Yi farmers which
      was predominantly driven by the discrepancy of body mass index between them.

PMID- 30287673
TI  - Study protocol for an observational register-based study on health and risk
      factors in patients with hip and knee osteoarthritis.
AB  - INTRODUCTION: Hip and knee osteoarthritis is a leading cause of disability
      worldwide. Currently, the course of deterioration in pain and physical
      functioning in individuals with osteoarthritis is difficult to predict. Factors
      such as socioeconomic status and comorbidity contribute to progression of
      osteoarthritis, but clear associations have not been established. There is a need
      for early identification of individuals with slow disease development and a good
      prognosis, and those that should be recommended for future joint replacement
      surgery. METHODS AND ANALYSIS: This nationwide register-based study will use data
      for approximately 75 000 patients who sought and received core treatment for
      osteoarthritis in primary healthcare, and were registered in the Swedish
      population-based National Quality Register for Better Management of Patients with
      Osteoarthritis. These data will be merged with data for replacement surgery,
      socioeconomic factors, healthcare consumption and comorbidity from the Swedish
      Hip Arthroplasty Register, the Swedish Knee Arthroplasty Register, Statistics
      Sweden and the National Board of Health and Welfare, Sweden. The linkage will be
      performed using personal identity numbers that are unique to all citizens in
      Sweden. ETHICS AND DISSEMINATION: The study was approved by the Regional Ethical
      Review Board in Gothenburg, Sweden (dnr 1059-16). The results from this study
      will be submitted to peer-reviewed journals and reported at suitable national and
      international meetings. TRIAL REGISTRATION NUMBER: NCT03438630.

PMID- 30287674
TI  - Research priorities in fragility fractures of the lower limb and pelvis: a UK
      priority setting partnership with the James Lind Alliance.
AB  - OBJECTIVE: To determine research priorities in fragility fractures of the lower
      limb and pelvis which represent the shared priorities of patients, their friends
      and families, carers and healthcare professionals. DESIGN/SETTING: A national
      (UK) research priority setting partnership. PARTICIPANTS: Patients over 60 years
      of age who have experienced a fragility fracture of the lower limb or pelvis;
      carers involved in their care (both in and out of hospital); family and friends
      of patients; healthcare professionals involved in the treatment of these patients
      including but not limited to surgeons, anaesthetists, paramedics, nurses, general
      practitioners, physicians, physiotherapists and occupational therapists. METHODS:
      Using a multiphase methodology in partnership with the James Lind Alliance over
      18 months (August 2016-January 2018), a national scoping survey asked respondents
      to submit their research uncertainties. These were amalgamated into a smaller
      number of research questions. The existing evidence was searched to ensure that
      the questions had not been answered. A second national survey asked respondents
      to prioritise the research questions. A final shortlist of 25 questions was taken
      to a multistakeholder workshop where a consensus was reached on the top 10
      priorities. RESULTS: There were 963 original uncertainties submitted by 365
      respondents to the first survey. These original uncertainties were refined into
      88 research questions of which 76 were judged to be true uncertainties following
      a review of the research evidence. Healthcare professionals and other
      stakeholders (patients, carers, friends and families) were represented equally in
      the responses. The top 10 represent uncertainties in rehabilitation, pain
      management, anaesthesia and surgery. CONCLUSIONS: We report the top 10 UK
      research priorities in patients with fragility fractures of the lower limb and
      pelvis. The priorities highlight uncertainties in rehabilitation, postoperative
      physiotherapy, pain, weight-bearing, infection and thromboprophylaxis. The
      challenge now is to refine and deliver answers to these research priorities.

PMID- 30287675
TI  - General practitioners and emergency departments (GPED)-efficient models of care:
      a mixed-methods study protocol.
AB  - INTRODUCTION: Pressure continues to grow on emergency departments in the UK and
      throughout the world, with declining performance and adverse effects on patient
      outcome, safety and experience. One proposed solution is to locate general
      practitioners to work in or alongside the emergency department (GPED). Several
      GPED models have been introduced, however, evidence of effectiveness is weak.
      This study aims to evaluate the impact of GPED on patient care, the primary care
      and acute hospital team and the wider urgent care system. METHODS AND ANALYSIS:
      The study will be divided into three work packages (WPs). WP-A; Mapping and
      Taxonomy: mapping, description and classification of current models of GPED in
      all emergency departments in England and interviews with key informants to
      examine the hypotheses that underpin GPED. WP-B; Quantitative Analysis of
      National Data: measurement of the effectiveness, costs and consequences of the
      GPED models identified in WP-A, compared with a no-GPED model, using
      retrospective analysis of Hospital Episode Statistics Data. WP-C; Case Studies:
      detailed case studies of different GPED models using a mixture of qualitative and
      quantitative methods including: non-participant observation of clinical care,
      semistructured interviews with staff, patients and carers; workforce surveys with
      emergency department staff and analysis of available local routinely collected
      hospital data. Prospective case study sites will be identified by completing
      telephone interviews with sites awarded capital funding by the UK government to
      implement GPED initiatives. The study has a strong patient and public involvement
      group that has contributed to study design and materials, and which will be
      closely involved in data interpretation and dissemination. ETHICS AND
      DISSEMINATION: The study has been approved by the National Health Service East
      Midlands-Leicester South Research Ethics Committee: 17/EM/0312. The results of
      the study will be disseminated through peer-reviewed journals, conferences and a
      planned programme of knowledge mobilisation. TRIAL REGISTRATION NUMBER:
      ISRCTN51780222.

PMID- 30287677
TI  - Diagnosing male infertility.

PMID- 30287676
TI  - Financial Incentives to Increase Uptake of Pediatric HIV Testing (FIT): study
      protocol for a randomised controlled trial in Kenya.
AB  - INTRODUCTION: Index case testing (ICT) to identify HIV-infected children is
      efficient but has suboptimal uptake. Financial incentives (FI) have overcome
      financial barriers in other populations by offsetting direct and indirect costs.
      A pilot study found FI to be feasible for motivating paediatric ICT among HIV
      infected female caregivers. This randomised trial will determine the
      effectiveness of FI to increase uptake of paediatric ICT. METHODS AND ANALYSIS:
      The Financial Incentives to Increase Uptake of Pediatric HIV Testing trial is a
      five-arm, unblinded, randomised controlled trial that determines whether FI
      increases timely uptake of paediatric ICT. The trial will be conducted in
      multiple public health facilities in western Kenya. Each HIV-infected adult
      enrolled in HIV care will be screened for eligibility: primary caregiver to one
      or more children of unknown HIV status aged 0-12 years. Eligible caregivers will
      be individually randomised at the time of recruitment in equal 1:1:1:1:1
      allocation to one of five arms (US$0 (control), US$1.25, US$2.50, US$5.00 and
      US$10.00). The trial aims to randomise 800 caregivers. Incentives will be
      disbursed at the time of child HIV testing using mobile money transfer or cash.
      Arms will be compared in terms of the proportion of adults who complete testing
      for at least one child within 2 months of randomisation and time to testing. A
      cost-effectiveness analysis of FI for paediatric ICT will also be conducted.
      ETHICS AND DISSEMINATION: This study was reviewed and approved by the University
      of Washington Institutional Review Board and the Kenyatta National Hospital
      Ethics and Research Committee. Trial results will be disseminated to healthcare
      workers at study sites, regional and national policymakers, and with patient
      populations at study sites (regardless of enrolment in the trial). Randomised
      trials of caregiver-child FI interventions pose unique study design, ethical and
      operational challenges, detailed here as a resource for future investigations.
      TRIAL REGISTRATION NUMBER: NCT03049917; Pre-results.

PMID- 30287678
TI  - Synthetic DNA-Encoded Monoclonal Antibody Delivery of Anti-CTLA-4 Antibodies
      Induces Tumor Shrinkage In Vivo.
AB  - Antibody-based immune therapies targeting the T-cell checkpoint molecules CTLA-4
      and PD-1 have affected cancer therapy. However, this immune therapy requires
      complex manufacturing and frequent dosing, limiting the global use of this
      treatment. Here, we focused on the development of a DNA-encoded monoclonal
      antibody (DMAb) approach for delivery of anti-CTLA-4 monoclonal antibodies in
      vivo With this technology, engineered and formulated DMAb plasmids encoding IgG
      inserts were directly injected into muscle and delivered intracellularly by
      electroporation, leading to in vivo expression and secretion of the encoded IgG.
      DMAb expression from a single dose can continue for several months without the
      need for repeated administration. Delivery of an optimized DMAb encoding anti
      mouse CTLA-4 IgG resulted in high serum levels of the antibody as well as tumor
      regression in Sa1N and CT26 tumor models. DNA-delivery of the anti-human CTLA-4
      antibodies ipilimumab and tremelimumab in mice achieved potent peak levels of
      approximately 85 and 58 MUg/mL, respectively. These DMAb exhibited prolonged
      expression, with maintenance of serum levels at or above 15 MUg/mL for over a
      year. Anti-human CTLA-4 DMAbs produced in vivo bound to human CTLA-4 protein
      expressed on stimulated human peripheral blood mononuclear cells and induced T
      cell activation in a functional assay ex vivo In summary, direct in vivo
      expression of DMAb encoding checkpoint inhibitors serves as a novel tool for
      immunotherapy that could significantly improve availability and provide broader
      access to such therapies.Significance: DNA-encoded monoclonal antibodies
      represent a novel technology for delivery and expression of immune checkpoint
      blockade antibodies, thus expanding patient access to, and possible clinical
      applications of, these therapies. Cancer Res; 78(22); 6363-70. (c)2018 AACR.

PMID- 30287680
TI  - p62-mediated phase separation at the intersection of the ubiquitin-proteasome
      system and autophagy.
AB  - The degradation of misfolded proteins is essential for cellular homeostasis.
      Misfolded proteins are normally degraded by the ubiquitin-proteasome system
      (UPS), and selective autophagy serves as a backup mechanism when the UPS is
      overloaded. Selective autophagy mediates the degradation of harmful material by
      its sequestration within double-membrane organelles called autophagosomes. The
      selectivity of autophagic processes is mediated by cargo receptors, which link
      the cargo to the autophagosomal membrane. The p62 cargo receptor (SQSTM1) has a
      main function during the degradation of misfolded, ubiquitylated proteins by
      selective autophagy; here it functions to phase separate these proteins into
      larger condensates and tether them to the autophagosomal membrane. Recent work
      has given us crucial insights into the mechanism of action of the p62 cargo
      receptor during selective autophagy and how its activity can be integrated with
      the UPS. We will discuss these recent insights in the context of protein quality
      control and the emerging concept of cellular organization mediated by phase
      transitions.

PMID- 30287679
TI  - Recurrent back pain during working life and exit from paid employment: a 28-year
      follow-up of the Whitehall II Study.
AB  - OBJECTIVES: To examine the impact of recurrent, as compared with single, reports
      of back pain on exit from paid employment over decades of follow-up. METHODS: The
      study sample was from the British Whitehall II Study cohort (n=8665, 69% men,
      aged 35-55 at baseline), who had provided information about their reports of back
      pain between 1985 and 1994. Data about exit from paid employment (health-related
      and non-health related exit, unemployment and other exit) were collected between
      1995 and 2013. Repeated measures logistic regression models were fitted to
      examine the associations, and adjust for covariates. RESULTS: Recurrent pain was
      reported by 18% of participants, while 26% reported pain on an occasion and 56%
      did not report pain. Report of back pain on an occasion was not associated with
      health-related job exit, whereas recurrent pain was associated with such an exit
      (OR 1.51; 95% CI 1.15 to 1.99), when compared with those who did not report pain.
      These associations were somewhat stronger among middle-grade and lower-grade
      employees, while these associations were not seen among higher-grade employees.
      Differences in associations by age and psychosocial working conditions were
      small. CONCLUSIONS: These results highlight the need for early detection of
      recurrent back pain to prevent exit out of paid employment for health reasons. As
      the risk varies by occupational grade, this emphasises the importance of
      identification of high-risk groups and finding ways to address their modifiable
      risk factors.

PMID- 30287682
TI  - Catastrophic haemorrhage in military major trauma patients: a retrospective
      database analysis of haemostatic agents used on the battlefield.
AB  - OBJECTIVES: Catastrophic haemorrhage is a leading cause of morbidity and
      mortality in trauma, in both military and civilian settings. There are numerous
      studies looking at the effectiveness of different haemostatic agents in the
      laboratory but few in a clinical setting. This study analyses the use of
      haemostatic dressings used in patients injured on the battlefield and their
      association with survival. METHOD: A retrospective database review was undertaken
      using the UK Joint Theatre Trauma Registry from 2003 to 2014, during combat
      operations in Iraq and Afghanistan. Data included patient demographics, the use
      of haemostatic dressings, New Injury Severity Score (NISS) and patient outcome.
      RESULTS: Of 3792 cases, a haemostatic dressing was applied in 317 (either Celox,
      Hemcon or Quickclot). When comparing patients who had a haemostatic dressing
      applied versus no haemostatic agent, there was a 7% improvement in survival.
      Celox was the only individual haemostatic dressing that was associated with a
      statistically significant improvement in survival, which was most apparent in the
      more severely injured (NISS 36-75). CONCLUSION: We have shown an association
      between use of haemostatic agents and improved survival, mostly in those with
      more severe injuries, which is particularly evident in those administered Celox.
      This supports the continued use of haemostatic agents as part of initial
      haemorrhage control for patients injured in conflict and suggests that civilian
      organisations that may need to deal with patients with similar injury patterns
      should consider their use and implementation.

PMID- 30287683
TI  - A comparison of CT lung voxel density analysis in a blast and non blast injured
      casualty.
AB  - INTRODUCTION: Primary blast lung injury (PBLI) is a prominent feature in
      casualties following exposure to blast. PBLI carries high morbidity and
      mortality, but remains difficult to diagnose and quantify. Radiographic diagnosis
      of PBLI was historically made with the aid of plain radiographs; more recently,
      qualitative review of CT images has assisted diagnosis. METHODS: We report a
      novel way of measuring post-traumatic acute lung injury using CT lung density
      analysis in two casualties. One casualty presented following blast exposure with
      confirmed blast lung injury and the other presented following extremity injury
      without blast exposure. Three-dimensional lung maps of each casualty were
      produced from their original trauma CT scan. Analysis of the lung maps allowed
      quantitative radiological comparison exposing areas of reduced aeration of the
      patient's lungs. RESULTS: 45% of the blast-exposed lungs were non-aerated
      compared with 10% in the non-blast-exposed lungs. DISCUSSION: In these example
      cases quantitative CT lung density analysis allowed blast-injured lungs to be
      distinguished from non-blast-exposed lungs.

PMID- 30287681
TI  - tRNA epitranscriptomics and biased codon are linked to proteome expression in
      Plasmodium falciparum.
AB  - Among components of the translational machinery, ribonucleoside modifications on
      tRNAs are emerging as critical regulators of cell physiology and stress response.
      Here, we demonstrate highly coordinated behavior of the repertoire of tRNA
      modifications of Plasmodium falciparum throughout the intra-erythrocytic
      developmental cycle (IDC). We observed both a synchronized increase in 22 of 28
      modifications from ring to trophozoite stage, consistent with tRNA maturation
      during translational up-regulation, and asynchronous changes in six
      modifications. Quantitative analysis of ~2,100 proteins across the IDC revealed
      that up- and down-regulated proteins in late but not early stages have a marked
      codon bias that directly correlates with parallel changes in tRNA modifications
      and enhanced translational efficiency. We thus propose a model in which tRNA
      modifications modulate the abundance of stage-specific proteins by enhancing
      translation efficiency of codon-biased transcripts for critical genes. These
      findings reveal novel epitranscriptomic and translational control mechanisms in
      the development and pathogenesis of Plasmodium parasites.

PMID- 30287684
TI  - The atlastin membrane anchor forms an intramembrane hairpin that does not span
      the phospholipid bilayer.
AB  - The endoplasmic reticulum (ER) is composed of flattened sheets and interconnected
      tubules that extend throughout the cytosol and makes physical contact with all
      other cytoplasmic organelles. This cytoplasmic distribution requires continuous
      remodeling. These discrete ER morphologies require specialized proteins that
      drive and maintain membrane curvature. The GTPase atlastin is required for
      homotypic fusion of ER tubules. All atlastin homologs possess a conserved domain
      architecture consisting of a GTPase domain, a three-helix bundle middle domain, a
      hydrophobic membrane anchor, and a C-terminal cytosolic tail. Here, we examined
      several Drosophila-human atlastin chimeras to identify functional domains of
      human atlastin-1 in vitro Although all chimeras could hydrolyze GTP, only
      chimeras containing the human C-terminal tail, hydrophobic segments, or both
      could fuse membranes in vitro We also determined that co-reconstitution of
      atlastin with reticulon does not influence GTPase activity or membrane fusion.
      Finally, we found that both human and Drosophila atlastin hydrophobic membrane
      anchors do not span the membrane, but rather form two intramembrane hairpin
      loops. The topology of these hairpins remains static during membrane fusion and
      does not appear to play an active role in lipid mixing.

PMID- 30287685
TI  - Simulations of the regulatory ACT domain of human phenylalanine hydroxylase
      unveil its mechanism of phenylalanine binding.
AB  - Phenylalanine hydroxylase (PAH) regulates phenylalanine (Phe) levels in mammals
      to prevent neurotoxicity resulting from high Phe concentrations as observed in
      genetic disorders leading to hyperphenylalaninemia and phenylketonuria. PAH
      senses elevated Phe concentrations by transient allosteric Phe binding to a
      protein-protein interface between ACT domains of different subunits in a PAH
      tetramer. This interface is present in an activated PAH tetramer (A-PAH) and
      absent in a resting-state PAH tetramer (RS-PAH). To investigate this allosteric
      sensing mechanism, here we used the GROMACS molecular dynamics simulation suite
      on the Folding@home computing platform to perform extensive molecular simulations
      and Markov state model (MSM) analysis of Phe binding to ACT domain dimers. These
      simulations strongly implicated a conformational selection mechanism for Phe
      association with ACT domain dimers and revealed protein motions that act as a
      gating mechanism for Phe binding. The MSMs also illuminate a highly mobile
      hairpin loop, consistent with experimental findings also presented here that the
      PAH variant L72W does not shift the PAH structural equilibrium toward the
      activated state. Finally, simulations of ACT domain monomers are presented, in
      which spontaneous transitions between resting-state and activated conformations
      are observed, also consistent with a mechanism of conformational selection. These
      mechanistic details provide detailed insight into the regulation of PAH
      activation and provide testable hypotheses for the development of new allosteric
      effectors to correct structural and functional defects in PAH.

PMID- 30287687
TI  - The C terminus of the bacterial multidrug transporter EmrE couples drug binding
      to proton release.
AB  - Ion-coupled transporters must regulate access of ions and substrates into and out
      of the binding site to actively transport substrates and minimize dissipative
      leak of ions. Within the single-site alternating access model, competitive
      substrate binding forms the foundation of ion-coupled antiport. Strict
      competition between substrates leads to stoichiometric antiport without slippage.
      However, recent NMR studies of the bacterial multidrug transporter EmrE have
      demonstrated that this multidrug transporter can simultaneously bind drug and
      proton, which will affect the transport stoichiometry and efficiency of coupled
      antiport. Here we investigated the nature of substrate competition in EmrE using
      multiple methods to measure proton release upon the addition of saturating
      concentrations of drug as a function of pH. The resulting proton-release profile
      confirmed simultaneous binding of drug and proton, but suggested that a residue
      outside EmrE's Glu-14 binding site may release protons upon drug binding. Using
      NMR-monitored pH titrations, we trace this drug-induced deprotonation event to
      His-110, EmrE's C-terminal residue. Further NMR experiments disclosed that the C
      terminal tail is strongly coupled to EmrE's drug-binding domain. Consideration of
      our results alongside those from previous studies of EmrE suggests that this
      conserved tail participates in secondary gating of EmrE-mediated proton-drug
      transport, occluding the binding pocket of fully protonated EmrE in the absence
      of drug to prevent dissipative proton transport.

PMID- 30287686
TI  - Oligomerization of the HECT ubiquitin ligase NEDD4-2/NEDD4L is essential for
      polyubiquitin chain assembly.
AB  - The NEDD4-2 (neural precursor cell-expressed developmentally down-regulated 4-2)
      HECT ligase catalyzes polyubiquitin chain assembly by an ordered two-step
      mechanism requiring two functionally distinct E2~ubiquitin-binding sites,
      analogous to the trimeric E6AP/UBE3A HECT ligase. This conserved catalytic
      mechanism suggests that NEDD4-2, and presumably all HECT ligases, requires
      oligomerization to catalyze polyubiquitin chain assembly. To explore this
      hypothesis, we examined the catalytic mechanism of NEDD4-2 through the use of
      biochemically defined kinetic assays examining rates of 125I-labeled
      polyubiquitin chain assembly and biophysical techniques. The results from gel
      filtration chromatography and dynamic light-scattering analyses demonstrate for
      the first time that active NEDD4-2 is a trimer. Homology modeling to E6AP
      revealed that the predicted intersubunit interface has an absolutely conserved
      Phe-823, substitution of which destabilized the trimer and resulted in a >=104
      fold decrease in k cat for polyubiquitin chain assembly. The small-molecule Phe
      823 mimic, N-acetylphenylalanyl-amide, acted as a noncompetitive inhibitor (Ki =
      8 +/- 1.2 mm) of polyubiquitin chain elongation by destabilizing the active
      trimer, suggesting a mechanism for therapeutically targeting HECT ligases.
      Additional kinetic experiments indicated that monomeric NEDD4-2 catalyzes only
      HECT~ubiquitin thioester formation and monoubiquitination, whereas polyubiquitin
      chain assembly requires NEDD4-2 oligomerization. These results provide evidence
      that the previously identified sites 1 and 2 of NEDD4-2 function in trans to
      support chain elongation, explicating the requirement for oligomerization.
      Finally, we identified a conserved catalytic ensemble comprising Glu-646 and Arg
      604 that supports HECT-ubiquitin thioester exchange and isopeptide bond formation
      at the active-site Cys-922 of NEDD4-2.

PMID- 30287689
TI  - ER stress signaling has an activating transcription factor 6alpha (ATF6)
      dependent "off-switch".
AB  - In response to an accumulation of unfolded proteins in the endoplasmic reticulum
      (ER) lumen, three ER transmembrane signaling proteins, inositol-requiring enzyme
      1 (IRE1), PRKR-like ER kinase (PERK), and activating transcription factor 6alpha
      (ATF6alpha), are activated. These proteins initiate a signaling and
      transcriptional network termed the unfolded protein response (UPR), which re
      establishes cellular proteostasis. When this restoration fails, however, cells
      undergo apoptosis. To investigate cross-talk between these different UPR enzymes,
      here we developed a high-content live cell screening platform to image
      fluorescent UPR-reporter cell lines derived from human SH-SY5Y neuroblastoma
      cells in which different ER stress signaling proteins were silenced through
      lentivirus-delivered shRNA constructs. We observed that loss of ATF6 expression
      results in uncontrolled IRE1-reporter activity and increases X box-binding
      protein 1 (XBP1) splicing. Transient increases in both IRE1 mRNA and IRE1 protein
      levels were observed in response to ER stress, suggesting that IRE1 up-regulation
      is a general feature of ER stress signaling and was further increased in cells
      lacking ATF6 expression. Moreover, overexpression of the transcriptionally active
      N-terminal domain of ATF6 reversed the increases in IRE1 levels. Furthermore,
      inhibition of IRE1 kinase activity or of downstream JNK activity prevented an
      increase in IRE1 levels during ER stress, suggesting that IRE1 transcription is
      regulated through a positive feed-forward loop. Collectively, our results
      indicate that from the moment of activation, IRE1 signaling during ER stress has
      an ATF6-dependent "off-switch."

PMID- 30287688
TI  - Role of phospholipid synthesis in the development and differentiation of malaria
      parasites in the blood.
AB  - The life cycle of malaria parasites in both their mammalian host and mosquito
      vector consists of multiple developmental stages that ensure proper replication
      and progeny survival. The transition between these stages is fueled by nutrients
      scavenged from the host and fed into specialized metabolic pathways of the
      parasite. One such pathway is used by Plasmodium falciparum, which causes the
      most severe form of human malaria, to synthesize its major phospholipids,
      phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Much is
      known about the enzymes involved in the synthesis of these phospholipids, and
      recent advances in genetic engineering, single-cell RNA-Seq analyses, and drug
      screening have provided new perspectives on the importance of some of these
      enzymes in parasite development and sexual differentiation and have identified
      targets for the development of new antimalarial drugs. This Minireview focuses on
      two phospholipid biosynthesis enzymes of P. falciparum that catalyze
      phosphoethanolamine transmethylation (PfPMT) and phosphatidylserine
      decarboxylation (PfPSD) during the blood stages of the parasite. We also discuss
      our current understanding of the biochemical, structural, and biological
      functions of these enzymes and highlight efforts to use them as antimalarial drug
      targets.

PMID- 30287691
TI  - [The Laterality of Parietal Association Areas: Hemispatial Neglect, Body Images
      and Body Schema].
AB  - This paper discusses the laterality of parietal association areas, focusing on
      hemispatial neglect and body representation. Extra-personal spatial neglect can
      be severe and is frequently observed following right parietal lesions; personal
      neglect is also common with right parietal lesions. According to the frame of
      awareness and perception, I speculate that the awareness of space is related to
      hemispatial neglect of extra-personal space, and awareness of body is related to
      personal neglect. Both clinical symptoms are common with right parietal lesions.
      On the other hand, I speculate that the perception of body is related to
      autotopagnosia, which could be associated with left parietal lesions.

PMID- 30287692
TI  - [Left and Right Hemispheric Contribution to Social Cognition].
AB  - Can we find hemispheric differences in the neural systems of social cognition?
      Social cognition is supported by a number of cognitive systems. Emotion plays an
      important role in understanding others and in controlling self-action. Theory of
      mind, the ability to infer the mental state of others, consists of subsystems
      such as empathy, mentalization, and perspective taking. Key brain structures for
      these cognitive processes are the medial prefrontal cortex, regions around the
      superior temporal sulcus, and the temporo-parietal junction. Most studies show
      right hemisphere dominance in emotional and social processes. With regard to the
      theory of mind, empathy is dominantly supported by the right hemisphere. However,
      some findings suggest the involvement of both hemispheres in mentalization and
      perspective talking. Social cognition is a complex process and should be
      considered as the consequence of inter-hemispheric processing involving several
      structures, although it is mainly right-hemisphere dominant.

PMID- 30287690
TI  - Scrambling of natural and fluorescently tagged phosphatidylinositol by
      reconstituted G protein-coupled receptor and TMEM16 scramblases.
AB  - Members of the G protein-coupled receptor and TMEM16 (transmembrane protein 16)
      protein families are phospholipid scramblases that facilitate rapid,
      bidirectional movement of phospholipids across a membrane bilayer in an ATP
      independent manner. On reconstitution into large unilamellar vesicles, these
      proteins scramble more than 10,000 lipids/protein/s as measured with co
      reconstituted fluorescent nitrobenzoxadiazole (NBD)-labeled phospholipids.
      Although NBD-labeled phospholipids are ubiquitously used as reporters of
      scramblase activity, it remains unclear whether the NBD modification influences
      the quantitative outcomes of the scramblase assay. We now report a refined
      biochemical approach for measuring the activity of scramblase proteins with
      radiolabeled natural phosphatidylinositol ([3H]PI) and exploiting the hydrolytic
      activity of bacterial PI-specific phospholipase C (PI-PLC) to detect the
      transbilayer movement of PI. PI-PLC rapidly hydrolyzed 50% of [3H]PI in large
      symmetric, unilamellar liposomes, corresponding to the lipid pool in the outer
      leaflet. On reconstitution of a crude preparation of yeast endoplasmic reticulum
      scramblase, purified bovine opsin, or purified Nectria haematococca TMEM16, the
      extent of [3H]PI hydrolysis increased, indicating that [3H]PI from the inner
      leaflet had been scrambled to the outer leaflet. Using transphosphatidylation, we
      synthesized acyl-NBD-PI and used it to compare our PI-PLC-based assay with
      conventional fluorescence-based methods. Our results revealed quantitative
      differences between the two assays that we attribute to the specific features of
      the assays themselves rather than to the nature of the phospholipid. In summary,
      we have developed an assay that measures scrambling of a chemically unmodified
      phospholipid by a reconstituted scramblase.

PMID- 30287693
TI  - [Lateralization of the Frontal Association Cortex: Syntax-related Networks].
AB  - The left inferior frontal gyrus, a part of the left frontal association cortex,
      is known to be involved in syntactic processing. Recently, we identified three
      syntax-related networks, which included each of the three regions of the left
      frontal association cortex. Moreover, patients with agrammatic comprehension
      caused by damage to the left association cortex showed changes in functional
      connectivity in the entire syntax-related network. These findings suggest that
      the left frontal association cortex is at the core of syntax-related networks.

PMID- 30287694
TI  - [The Current Status of Corpus Callosotomy for Epilepsies].
AB  - Surgery is considered a therapeutic option for drug-resistant epilepsies. As a
      first step, the epileptic focus is carefully examined using extra- and intra
      cranial EEG and various neurodiagnostic imaging techniques, such as magnetic
      resonance imaging, intra-ictal single photon emission computed tomography,
      magnetoencephalography, and functional near-infrared spectoroscopy. Only when the
      epileptogenic focus can not be identified, callosotomy is considered as a
      palliative surgical method. It is indicated especially in cases with drop
      attacks, which severely exacerbate the patient's quality of life. Almost complete
      drop attack remission can be expected after callosotomy. Each year, about 40
      cases of callosotomy are registered in Japan. Postsurgical split-brain syndromes
      are observed for several months and gradually disappear, especially in young
      children.

PMID- 30287695
TI  - [Right-versus Left-handedness in Behavioral and Cognitive Neuroscience].
AB  - Globally, approximately 90% of individuals are right-handed, while the remaining
      10% are left-handed. Handedness is associated with functional lateralization of
      cerebral dominance, and may also be associated with various types of
      psychological characteristics. Unfortunately, neuromyths of left handedness have
      become deeply embedded in public consciousness due to misleading studies. In
      neuroscience research, it is common for left-handed individuals to be excluded
      from study cohorts in an attempt to increase data uniformity. Left-handed
      participants represent a substantial portion of the population and their
      inclusion of left-handed participants can be informative in studies of cerebral
      asymmetry. We should aim to construct a society that allows people with diverse
      characteristics, such as left-handed individuals live without discomfort or
      stress.

PMID- 30287696
TI  - [Superficial Siderosis].
AB  - Superficial siderosis (SS) is a rare, neurodegenerative disease that results from
      toxic accumulation of hemosiderin on the surface of the brain and spinal cord.
      The Japanese guidelines for diagnosis and classification of SS have been
      classified into three categories, according to the distribution of iron
      deposition and the clinical symptoms, as follows: "classical" type, "localized"
      type and "atypical" type. In "classical" type SS, patients typically present with
      slowly progressive and irreversible cerebellar ataxia, sensorineural hearing
      loss, and/or myelopathy, due to involvement of the acoustic nerve, cerebellum,
      and spinal cord. T2-weighted imaging (WI) or T2<sup>*</sup> WI demonstrates
      characteristic linear low intensity signals along the surface of the brain and
      spinal cord. However, the natural history and clinical evolution of SS are poorly
      understood. Furthermore identification and resolution of the bleeding source do
      not elicit prompt clinical recovery or radiological reversal of SS in most cases.
      Pharmacological treatments for SS primarily include strategies that produce iron
      chelation. For example, deferiprone is the only treatment that crosses the blood
      brain barrier and binds hemosiderin in the central nervous system.

PMID- 30287697
TI  - [A Case of Neuromyelitis Optica Spectrum Disease with Hypoglycorrhachia].
AB  - A 75-year-old Japanese woman developed myelitis 3years prior to her admission.
      She was diagnosed with HTLV-1-related myelitis and had taken prednisolone. Her
      myelitis relapsed several times, and serum aquaporin-4 was positive in an ELISA.
      She developed a sudden headache, consciousness disturbance, dysarthria, and left
      limb paralysis, and was admitted to our hospital. The CSF analysis revealed
      pleocytosis dominated by morphonuclear cells and hypoglycorrhachia. Magnetic
      resonance imaging revealed abnormalities in the corpus callosum, bilateral
      thalamus, and corticospinal tracts. We initially suspected a relapse of
      neuromyelitis optica spectrum disorder (NMOSD) and infection. We treated the
      patient with methylprednisolone pulse and antibacterial and antiviral treatment,
      which were not effective. Plasmapheresis was performed five times, and she
      gradually improved. Immunosuppressive treatment was added. It is rare for NMOSD
      to cause hypoglycorrhachia. This case suggests that infection may trigger an
      autoimmune response in NMOSD. (Received February 13, 2018; Accepted July 12,
      2018; Published October 1, 2018).

PMID- 30287698
TI  - [Listeria Brainstem Encephalitis with Brain Abscess in an Elderly Healthy Woman].

PMID- 30287699
TI  - Scope of Mathematical Biology in Cancer Research.
AB  - Mathematical biology involves the use of mathematical models derived from
      biological data to predict the course or outcome of a biological event. In
      oncology, mathematics plays a vital role in determining the tumor behavior and
      the optimal treatment strategy including the right combination of treatment
      modality to be used, and the timing and duration of the treatment. The major
      limiting factor in mathematical oncology is the inability to obtain accurate
      biological data to formulate appropriate mathematical models.1 Development of
      molecular biology has enabled us to overcome these limitations.

PMID- 30287700
TI  - Oral Lesions found in a Dental School in Southern Brazil.
AB  - OBJECTIVE: This study aimed to perform an epidemiological survey of the cases of
      oral lesions diagnosed in a Brazilian dental school. MATERIALS AND METHODS: An
      epidemiological survey was carried out at the Faculty of Dentistry of the
      University of Passo Fundo (FOUPF), Rio Grande do Sul, Brazil, between March 2015
      and June 2017, characterizing the patients in terms of gender, age, and
      ethnicity. A total of 3,200 records were evaluated, from which 716 presented
      information on oral lesions diagnosed and treated at the clinics of the FOUPF.
      The data were evaluated by descriptive statistics of frequency. RESULTS: The most
      frequent change was the coated tongue (13.83%). The majority of the patients were
      female (56%), white (31.57%), in the sixth decade of life (21.65%). Regarding the
      classification of lesions, the most frequent group was developmental changes
      (25%). CONCLUSION: It is considered that the sample studied presented a
      significant index of oral lesions and normality changes, considering that 716
      (22.38%) patients studied showed some type of change in the oral cavity. CLINICAL
      SIGNIFICANCE: The sample studied presents peculiar characteristics regarding the
      number of oral lesions/conditions diagnosed. It is also considered that Schools
      of Dentistry are valuable environments for carrying out epidemiological surveys
      in stomatology, providing the diagnostic exercise, as long as the students are
      stimulated for this purpose.

PMID- 30287701
TI  - Effectiveness of Mentha piperita Leaf Extracts against Oral Pathogens: An in
      vitro Study.
AB  - AIM: The study aims to assess the Mentha piperita leaf extract's effectiveness
      against oral pathogens. MATERIALS AND METHODS: The leaf extract of M. piperita
      was prepared using cold water method. The three microbial strains, i.e.,
      Streptococcus mutans, Aggregatibacter actinomycetem-comitans, and Candida
      albicans were used as microbiological materials. Chlorhexidine 0.2% was used as
      positive control. The digital caliper was used to measure the zone of inhibition
      to know the antimicrobial activity at 24 and 48 hours. To compare the activity
      within and between the different microbial strains, one-way analysis of variance
      (ANOVA) was used. To analyze the data, Statistical Package for the Social
      Sciences (SPSS) software version of 21.0 was used. The p-value <=0.05 was
      considered as statistically significant. RESULTS: Maximum inhibition zone was
      seen in both M. piperita extracts and 0.2% chlorhexidine with S. mutans at 24 and
      48 hours, followed by A. actinomycetemcomitans, and C. albi-cans respectively.
      The statistical analysis ANOVA reveals the statistically significant association
      of M. piperita extracts with p-value <0.001. The comparison with 0.2%
      chlorhexidine at 24 hours showed a p-value of <0.04 and at 48 hours, it showed a
      p-value <0.001, which was statistically significant. CONCLUSION: The present
      study concluded that M. piperita showed antimicrobial activity against the oral
      microorganisms which are causing major less or more severe oral diseases and it
      can be administered as an alternative medicine for the conventional treatment.
      CLINICAL SIGNIFICANCE: The study results serve as a guide in selecting and
      providing information about the efficacy of M. piperita extracts to the dental
      professionals. The discovery of a potential herbal medication would be a great
      development in the field of antimicrobial therapies.

PMID- 30287702
TI  - In vitro Analysis of Shear Bond Strength and Adhesive Remnant Index of Stainless
      Steel Brackets with Different Adhesive Systems to Enamel.
AB  - AIM: This study aimed at evaluating and comparing the bond strength of stainless
      steel brackets bonded with multiple orthodontic adhesives. MATERIALS AND METHODS:
      About 60 premolars extracted to create space during orthodontic treatment were
      included in the present study. Premolar stainless steel brackets of size 0.022"
      slot with the surface area of bracket base of 11.15 mm2 were used. The premolars
      were divided randomly into three groups of 20 in each. Group I: Conventional Acid
      Etching (Transbond XT); group II: Seventh-generation adhesive materials (Xeno V);
      and group III: Flowable composite (Filtek Z350 XT). Calculation of Adhesive
      Remnant Index (ARI) was done and shear bond strength was assessed. The
      probability level of 0.05 was considered as clinically significant. RESULTS: The
      shear bond strength was highest in group II (17.46 +/- 1.36), which was followed
      by group I (15.33 +/- 2.78) and the least was shown by group III (13.96 +/-
      1.44). A statistically significant difference was found between group I vs II,
      group II vs III, and group III vs II. Utmost prevalence of about 35% was found in
      Transbond XT with an ARI score of 3 (followed by all adhesive left on the tooth),
      Filtek Z350 XT with 20%, and the least was found with Xeno V, about 5%. The
      probability was found to be p = 0.025 among different groups, which is
      statistically significant according to chi-square test. CONCLUSION: The study
      concluded that the adhesive materials of the seventh generation showed higher
      shear bond strength than that of the flowable composite and conventional acid
      etching. The ARI indicated that a minimum amount of the residual adhesive was
      found on the surface of the enamel after debonding. CLINICAL SIGNIFICANCE: This
      study helps orthodontists to select appropriate adhesive and orthodontic brackets
      for the benefit of the patient and to distinguish the distribution of stress
      homogeneously within the layer of cement while loading and subsequently
      minimizing the damage to the enamel during the debonding of orthodontic brackets.

PMID- 30287703
TI  - Influence of Restoration Height and Masticatory Load Orientation on Ceramic
      Endocrowns.
AB  - AIM: Endocrown restorations are an alternative to restore end-odontically treated
      teeth. Due to the fact that in the literature it is recommended a remnant of 1.5
      mm, different heights of endocrown were elaborated and analyzed, obtaining
      possible faults and their location. This study aimed to evaluate the mechanism of
      stress distribution in the tooth/restoration set, varying two factors:
      "restoration height"-three levels, and load application-two levels (oblique or
      axial), totaling six groups. MATERIALS AND METHODS: For finite element analysis
      (FEA), a maxillary premolar was modeled with an endodontic treatment. Then, this
      template was triplicated and each copy received an endocrown restoration of
      different heights: G6 (4.5 mm), G7 (5.5 mm), and G8 (6.5 mm). The models were
      exported in STEP format to analysis software (ANSYS 17.2, ANSYS Inc.). During
      preprocessing, the solids were considered isotropic, linearly elastic, and
      homogeneous. Initially, a load (300 N) was axially applied in the central fossa
      region. For a second evaluation, an oblique load (300 N) was applied on the
      grinding slope of functional cusp. System fixation occurred at the base of poly
      urethane cylinder. Results were evaluated through maximum principal stress (MPS).
      RESULTS: For axial load, lower stress values were generated in all groups. For
      oblique load, G8 showed a higher stress concentration in the cement layer and
      root dentin. CONCLUSION: When an endocrown restoration is performed, there is a
      tendency of failure in the cement line and in the root directly proportional to
      its size. However, regardless of the size of the element to be reconstituted, the
      axial direction of the masticatory loads tends to decrease stress concentration.
      CLINICAL SIGNIFICANCE: When performing an endocrown restoration, care must be
      taken with its high regardless the tooth remnant high, altering even the
      anatomical angulations of the occlusal face, when necessary, to avoid stress
      concentration in thick areas.

PMID- 30287704
TI  - Control of Anxiety in Pediatric Patients using "Tell Show Do" Method and
      Audiovisual Distraction.
AB  - INTRODUCTION: Visiting a dentist can easily evoke strong fear reactions and acute
      anxiety in children. It is one of the most basic reasons for avoidance and
      neglect of dental care. It may obstruct delivery of dental care, as the child may
      be unwilling to accept the treatment being provided by the dentist. AIM: To
      evaluate and compare reduction in anxiety level in patients undergoing dental
      treatment at first dental visit. TECHNIQUE: The study was conducted on 400
      patients coming to the Department of Pedodontics and Preventive Dentistry, Guru
      Teg Bahadur Hospital, University College of Medical Sciences, New Delhi, for
      their first dental visit. Anxiety was recorded using facial image scale (FIS),
      Venham's picture test (VPT), blood pressure, pulse rate (PR), and oxygen
      saturation (SpO2) at different stages of the visit. Patients coming for the first
      dental visit were subjected to restorative treatment under Tell show do (TSD)
      method and audiovisual distraction (AVD). The data collected were tabulated and
      subjected to statistical analysis. CONCLUSION: The AVD was found to be more
      capable in reducing anxiety than TSD. Combination of TSD and AVD had an additive
      effect in reduction of anxiety level and it proved to be more beneficiary.
      CLINICAL SIGNIFICANCE: If a child's behavior in the dental office cannot be
      managed, then it is difficult to hold out any dental treatment that is needed.
      Bringing positivity in the child's behavior would not only increase efficiency of
      work but would also make the experience for child undergoing treatment more
      pleasant.

PMID- 30287705
TI  - Study to evaluate the Efficacy of Resin-modified Glass lonomer Cement Liner as a
      Direct Pulp Capping Material.
AB  - AIM: The aim of the present in vivo study was to compare efficacy of light-cured
      resin-modified glass ionomer liner, VitrebondTM (3M ESPE) with Dycal(r)
      (Dentsply) on the healing of pulpal tissue in the event of a direct iatrogenic
      pulpal exposure. MATERIALS AND METHODS: Experimental group consisted of
      VitrebondTM (3M ESPE) resin-modified glass ionomer liner, and VitremerTM (3M
      ESPE) resin-modified glass ionomer cement (GIC) in comparison with the control
      group of Dycal(r) (Dentsply) as liner and Poly F(r) (Dentsply) dental cement.
      Class V cavities were prepared in 32 sound premolars that were scheduled for
      orthodontic extraction, and the exposures were capped according to groups. Five
      teeth from each group were extracted under local anesthesia after an interval of
      24 hours, 35 and 60 days, and evaluated for inflammation, fibrotic changes,
      formation of reparative dentin and bacterial examination. RESULTS: The present
      study did not show any statistically significant difference between two groups in
      terms of inflammation, fibrosis, reparative dentin formation, and bacterial
      examination. CONCLUSION: This study shows that VitrebondTM (3M ESPE) light-cured
      resin-modified glass ionomer liner can be used as an alternative to calcium
      hydroxide as a direct pulp capping material. CLINICAL SIGNIFICANCE: Light-cured
      resin-modified glass ionomer liner can be an alternative for the calcium
      hydroxide-based liner for capping iatrogenic pulp exposures.

PMID- 30287706
TI  - Eruption of Impacted Teeth in Cleft Lip and Palate Patients following Alveolar
      Bone Graft.
AB  - INTRODUCTION: This study aimed to assess the eruption of impacted teeth in cleft
      lip and/or palate (CLP) after alveolar bone graft. MATERIALS AND METHODS:
      Research was carried out through a cross-sectional study at the Craniofacial
      Rehabilitation Center of the University General Hospital of the University of
      Cuiaba, Mato Grosso, Brazil. Variables related to cleft, cleft side, gender, age,
      laterality of cleft, impacted teeth, and orthodontic traction were analyzed.
      RESULTS: Forty-two patients treated at the institution from 2004 to 2011 had
      their charts retrospectively reviewed. They were 54.7% male and 45.2% female. The
      group aged 9 to 11 years was most affected, representing 59.5% of cases. A
      unilateral cleft was the most prevalent craniofacial anomaly (85.7%). A total of
      57 impacted teeth were observed. Maxillary canines were the most commonly
      impacted teeth (97.6%) and the most frequently identified in patients with a
      transforamen incisor cleft (TIC) (76.3%). Orthodontic traction was required for
      both impacted maxillary canines and impacted lateral incisors (64.3 and 35.7%
      respectively). The orthodontic traction was required only in patients with a TIC
      (p = 0.0101). CONCLUSION: The canine teeth were the most commonly impacted teeth,
      found mainly in patients with a TIC. After placement of the alveolar bone graft
      in patients with a preforamen incisor cleft (PIC), all impacted teeth erupted
      spontaneously. CLINICAL SIGNIFICANCE: An impacted tooth can have negative
      consequences on a patient's quality of life. Thus, a survey evaluating the
      incidence and prognosis of impacted teeth after an alveolar bone graft for CLP
      was important.

PMID- 30287707
TI  - Comparative Study of Micronuclei Count in Patients with Different Tobacco-related
      Habits using Exfoliated Buccal Epithelial Cells: A Tool for Assessment of
      Genotoxicity.
AB  - AIM: To study and compare the genotoxic effects of tobacco using micronuclei
      count in individuals with different tobacco-related habits. MATERIALS AND
      METHODS: A cross-sectional study was done comprising 200 individuals, divided
      into four groups. Group I: 50 subjects with history of tobacco chewing, group II:
      50 subjects with a history of smoking tobacco, group III: 50 subjects with a
      history of both tobacco chewing and smoking, and group IV: 50 subjects without
      any habits as controls (age-matched). The study groups were individually further
      divided into three subgroups which comprised of subjects with history of
      substance abuse for less than 5, 5 to 10, and greater than 10 years. Exfoliated
      cells from the buccal mucosa of the subjects were collected and stained using
      Giemsa stain. A total of 1,000 cells were examined for each case and micronuclei
      frequency was scored according to the guidelines given by Tolbert et al. Results:
      The mean number of micronuclei count was 18.28 +/- 10.0 in group I (smokeless
      tobacco users), 11.38 +/- 6.3 in group II (subjects with history of tobacco
      smoking), 22.44 +/- 9.8 in group III (subjects with history of using both
      smokeless and smokable form of tobacco), and 4.86 +/- 2.4 in the control group.
      The statistical difference was found to be highly significant (p < 0.001).
      Similarly, based on the duration, highly significant difference was notable in
      the mean number of micronuclei in subjects who had a history of substance abuse
      for more than 10 years. CONCLUSION: A significantly higher micronucleus frequency
      was found in smokeless tobacco users than in smokers and controls. Micronuclei
      assay in the exfoliated buccal cells is a useful and minimally invasive method
      for monitoring early genotoxic damage. CLINICAL SIGNIFICANCE: Micronuclei assay
      can be used to detect genotoxic damage at the earliest and, if intervened at this
      point, may prevent frank malignancy, morbidity, and mortality.

PMID- 30287708
TI  - Comparative Evaluation of Shear Bond Strength and Microleakage of Two Self
      adhering Composite Resins: An in vitro Study.
AB  - INTRODUCTION: A good dental cement used as repair material should possess
      chemical binding, easy handling characteristics, minimal marginal breakdown and
      minimal polymerization shrinkage, high resistance to wear, high cohesive
      strength, and good color stability. This study was undertaken to compare the in
      vitro microleakage and shear bond strength among the newly introduced Prime fill
      flow and Dyad flow. AIM: The aim of this study was to determine the effect on
      shear bond strength and microleakage of two self-adhesive composite resin.
      MATERIALS AND METHODS: Selected specimens were collected and stored in deionized
      water with an antibactericidal agent, 0.2% sodium azide, until ready to be used
      and were randomly divided into two groups: group I: Dyad flow and group II: Prime
      fill flow; specimens were sheared with a universal testing machine, and the
      results were calculated in megapascal, specimens were sectioned in a mesiodistal
      direction at four different locations, and analyzed for leakage (dye penetration)
      using a stereomicroscope. RESULTS: The results of the present study showed that
      acceptable values for Prime fill flow seemed to have least microleakage and high
      bond strength as compared with Dyad flow. CONCLUSION: Here, it can be concluded
      that there was significant difference in the in vitro microleakage and shear bond
      strength among the Prime fill flow and Dyad flow. CLINICAL SIGNIFICANCE: Self
      etch adhesives when compared with total-etch systems have the advantage of
      reducing the application time and the number of steps in pediatric dentistry.
      Patients' age and cooperation are not always ideal; the treatment outcome is
      greatly influenced by the patients' behavior. It is therefore imperative to
      recede the application time of some materials mostly in pediatric dentistry.

PMID- 30287709
TI  - Evaluation of Influence of Widening Apical Preparation of Root Canals on
      Efficiency of Ethylenediaminetetraacetic Acid Agitation Protocols: Study by
      Scanning Electron Microscopy.
AB  - AIM: The purpose of this study was to evaluate the influence of widening the
      apical root canal preparation (RCP) on the efficiency of different
      ethylenediaminetetraacetic acid (EDTA) agitation protocols on smear layer
      removal: EDTA; EDTA + Easy Clean in rotary movement (ECROT); EDTA + Easy Clean in
      reciprocating movement (ECREC); and EDTA + Passive ultrasonic irrigation (PUI).
      MATERIALS AND METHODS: A total of 80 mandibular premolars had their crowns
      sectioned and then were divided into two groups according to widening: size 25 or
      40, 0.08 taper. Sequentially they were once again allocated to subgroups
      according to the agitation protocol performing eight experimental groups (n =
      10). Ten additional teeth were prepared for controls (C+/C-). The specimens were
      then submitted to the cleaning protocols and thereafter cleaved and
      microphotographed by variable pressure scanning electron microscopy (SEM) at
      previously determined points along their root thirds (750*). Scores were
      attributed to the images, and data were analyzed by the Kruskal-Wallis, Student
      Newman-Keuls and Friedman tests. RESULTS: A higher widening was observed to have
      a positive influence on cleaning efficiency offering significant differences in
      global and apical third evaluations (p < 0.05). Relative to the agitation,
      significant differences were observed mainly in the apical third, with PUI and
      ECROT providing the best results (p < 0.05); no difference for C+ was observed
      when higher widening was employed. CONCLUSION: A greater widening of the apical
      third provided a significant improvement in the action of the
      agitation/activation protocols. Moreover, the PUI and ECROT activation methods
      were shown to be superior to the use of EDTA solely, particularly in the apical
      third. CLINICAL SIGNIFICANCE: The findings of this study reinforce the need for
      clinical use of additional methods to complement cleaning. Therefore, it is
      important for professionals to have knowledge and command of these protocols to
      obtain more satisfactory results.

PMID- 30287710
TI  - A Retrospective Analysis of Pulp Stones in Patients following Orthodontic
      Treatment.
AB  - AIM: The present study aimed to find prevalence of pulp stones in known South
      Indian orthodontic patients and to find correlation between pulp stones and
      patients who underwent orthodontic treatment as well as to reveal any differences
      due to gender, tooth type, and dental arches. MATERIALS AND METHODS: The present
      retrospective study was carried out among 200 patients who underwent
      nonextraction orthodontic treatment. Maxillary and mandibular first and second
      premolar and molar teeth were selected for the purpose of the study using
      panoramic radiographs. A total of 3200 teeth of 200 patients were studied for the
      presence of pulp stones. Statistical analysis of the obtained data was carried
      out using Statistical Package for Social the Sciences (SPSS) version 22.0. Chi
      square test was applied to find the significant value and p < 0.05 was considered
      as a significant value. RESULTS: In all, 11.5% of cases reported pulp stones
      before the commencement of the orthodontic treatment and 15.5% cases after
      completion of orthodontic treatment. Overall, 4% increase in cases were found
      which was statistically significant (p < 0.05); 5.1% of total number of teeth
      were evaluated in both arches before orthodontic treatment and 6.3% of teeth
      after orthodontic treatment revealed the presence of pulp stones. Maxillary first
      molar was found to be teeth with maximum number of pulp stones before and after
      orthodontic treatment. CONCLUSION: The present study reported the prevalence of
      pulp stones to be increased by 4% in the pre- and posttreat-ment radiographs,
      which was statistically significant. The study found the presence of pulp stones
      more in maxillary first molar and it was found to be teeth with maximum number of
      pulp stones before and after orthodontic treatment. However, further researches
      with larger samples are advisable. CLINICAL SIGNIFICANCE: Dentists performing
      endodontic treatment among patients who have undergone orthodontic treatment
      should be aware about the increased chances of presence of pulp stones and thus
      to avoid hindrances encountered during extirpating the pulp, they should
      thoroughly study the radiographs beforehand.

PMID- 30287711
TI  - In vitro Evaluation and Comparison of Microleakage of Two Restorative Composite
      Resins in Class II Situations using Confocal Laser Scanning Microscopy.
AB  - AIM: The placement of composite in teeth is not an easy task and it poses many
      challenges. Microleakage is one of the factors that affects the success of any
      composite restoration. It influences the longevity of dental restorations. The
      present study was aimed to evaluate and compare microleakage of two restorative
      composites resins in class II cavities using confocal laser scanning microscopy
      (CLSM). MATERIALS AND METHODS: This was an in vitro study, which included 20
      permanent mandibular first molar. On each tooth, 40 class II cavities were
      prepared with a carbide bur. The teeth were then randomly divided into two groups
      of 10 each. Group I included teeth in which SonicFill Bulk Fill composite was
      used. Group II included teeth in which Tetric EvoCeram Bulk Fill composite was
      used. The microleakage was measured using confocal microscopy at 10*
      magnification in the fluorescent mode by a scoring system. RESULTS: Estimation
      was done at cervical and occlusal levels, wherein group I included 10 teeth which
      were restored with SonicFill Bulk Fill composite and group II included 10 teeth
      which were restored with Tetric EvoCeram Bulk Fill composite. Microleakage was
      quantified on scoring basis, which was consecutively based on the dye penetration
      at different levels. Data thus obtained statistically revealed that microleakage
      was comparatively more in group II as compared with group I. In addition, it was
      somewhat similar on both cervical as well as occlusal regions. The difference was
      significant (p = 0.05). Comparison was also done at cervical and occlusal levels
      using Wilcoxon signed-rank test, which showed significant levels of differences
      (p > 0.05). CONCLUSION: There is more microleakage in Tetric EvoCeram Bulk Fill
      composite as compared with SonicFill Bulk Fill composite. CLINICAL SIGNIFICANCE:
      No material seems to totally eliminate microleakage in class II situations with
      gingival margin ended in dentine. However, CLSM is a useful tool in microleakage
      evaluation that could be used successfully to estimate the severity of microbial
      penetrations and material of choice as well.

PMID- 30287712
TI  - Role of E-cadherin in Progression of Oral Squamous Cell Carcinoma: A
      Retrospective Immunohistochemical Study.
AB  - AIM: The aim of present study was to assess the role of E-cadherin in oral
      carcinogenesis by comparing their expressions in normal oral mucosa, oral
      epithelial dysplasia (OED), and oral squamous cell carcinoma (OSCC). MATERIALS
      AND METHODS: To elucidate the pattern of E-cadherin expression in oral
      carcinogenesis, 21 archival cases of formalin-fixed paraffin-embedded sections of
      OSCC, 21 OED, and 7 normal oral mucosa samples as control were used for the
      study. RESULTS: We observed reduction/loss of E-cadherin in membranous expression
      pattern and staining intensity with progression from dysplasia to oral cancer.
      CONCLUSION: A decrease in staining intensity and loss of E-cadherin membranous
      expression were noted from dysplasia to carcinoma, suggesting its role as a tumor
      suppressor gene. CLINICAL SIGNIFICANCE: E-cadherin can be used as a biomarker to
      assess and evaluate the progression and prognosis of oral dysplastic lesions and
      OSCC.

PMID- 30287713
TI  - Wound Healing in Dental Implant Surgery in Patients with or without Antibiotic
      Prophylaxis.
AB  - AIM: To assess the association of various clinical parameters and proinflammatory
      cytokines in the wound-healing process of dental implants with the presence or
      absence of antibiotic prophylaxis. MATERIALS AND METHODS: The present study
      included evaluation of early wound-healing process in patients undergoing dental
      implant placement procedures with and without antibiotic prophylaxis. A total of
      50 patients with partial edentulous arch were included in the present study. All
      the subjects were broadly divided into two study groups depending upon the
      presence or absence of prophylactic antibiotic therapy, with 25 patients in each
      group. One group consisted of subjects who were given prophylactic amoxicillin (2
      gm), 1 hour before the starting of the surgery, followed by 500 mg 3 times a day
      for 1 week. Detection of interleukin (IL)-1beta and -8 cytokine levels in the
      gingival crevicular fluid (GCF)/peri-implant crevicular fluid (PICF) was done
      immediately after the dental surgery. All the results were compiled and analyzed
      by Statistical Package for the Social Sciences (SPSS) software version 17.0.
      RESULTS: A significant increase in the PICF IL-1beta concentration at
      postoperative follow-up time was observed in the antibiotic group in comparison
      with the baseline values. A significant increase in the IL-8 concentration
      postoperatively in comparison with the baseline values in the antibiotic group
      was also observed. At the time of surgery, the IL-8 concentrations were
      statistically lower in the antibiotic group in comparison with the other study
      group. Concentration of amoxicillin, as observed by high-performance liquid
      chromatography (HPLC), was lower than the minimum detection levels. CONCLUSION:
      Detection of amoxicillin is not feasible within the GCF samples immediately after
      dental surgery procedure. CLINICAL SIGNIFICANCE: Clinical usefulness of
      prophylactic use of amoxicillin is still doubtful.

PMID- 30287714
TI  - Comparative Evaluation of the Efficacy of Intraligamentary and Supraperiosteal
      Injections in the Extraction of Maxillary Teeth: A Randomized Controlled Clinical
      Trial.
AB  - AIM: The aim of this clinical trial was to compare the efficiency of the
      intraligamentary (periodontal ligament) injection with supraperiosteal injections
      in extraction of maxillary teeth, using pain during injection and extraction as
      the parameters. MATERIALS AND METHODS: Thirty patients indicated for extraction
      of maxillary molars were randomly allocated into one of the following
      intervention groups (n = 15): intraligamentary injection and supraperiosteal
      injection. In both groups, anesthesia was given using a standard volume of 2%
      lignocaine with adrenaline 1:2,00,000 with a 27G needle. Patients indicated pain
      during injection and extraction and this was measured using the visual analog
      scale (VAS). Statistical analysis of the pain scores was done using chi-square
      test, Levene's test, and Mann-Whitney U test with the alpha error set at p =
      0.05. RESULTS: The mean VAS score for pain during injection was higher for the
      intraligamentary injection group (VAS = 18.67) than for the supraperiosteal
      infiltration group (VAS = 16), but this was not statistically significant (p >
      0.05). The VAS score during extraction was significantly higher for the
      intraligamentary injection group (VAS = 34.67) than for the infiltration group
      (VAS = 20) (p < 0.05). CONCLUSION: Periodontal ligament injections may not be
      optimal, "stand-alone" alternatives to supraperiosteal injections in the
      exodontia of maxillary teeth. CLINICAL SIGNIFICANCE: Intraligamentary or
      periodontal injections are useful in extractions on patients with bleeding
      disorders, as they eliminate the risk of encountering blood vessels during
      injections as in the case of nerve blocks. The efficacy of intraligamentary
      injections in extraction of mandibular teeth has been widely studied. This study
      evaluates the efficacy of this alternate injection technique on maxillary teeth
      extraction and, if proved successful, can be useful in patients where
      supraperiosteal injections are contraindicated.

PMID- 30287715
TI  - A Novel Mobile Health Approach to Early Diagnosis of Oral Cancer.
AB  - AIM: The incidence of oral cancer is high in India, which can be reduced by early
      detection. We aimed to empower frontline health care providers (FHP) for early
      detection and connect specialist to rural population through mHealth. MATERIALS
      AND METHODS: We provided training to FHPs in examination of oral cavity, use of
      mobile phone for image capture, and risk factor analysis. The FHPs were selected
      from different cohorts in resource-constrained settings. The workflow involved
      screening of high-risk individuals in door-to-door and workplace settings, and
      capture of images of suspected lesions. Uploaded data were interpreted and
      recommendation was sent by specialist from a remote location. Their
      recommendation was intimated to FHPs who arranged for further action. Two more
      initiatives, one for multiple dental schools and another for private
      practitioners, were undertaken. RESULTS: During the period from 2010 to 2018,
      42,754 subjects have been screened, and 5,406 subjects with potentially malignant
      disorders have been identified. The prevalence of potentially malignant disorders
      varied from 0.8 to 62% at different cohorts; 516 biopsies have been performed at
      remote locations. CONCLUSION: Connecting specialists to rural population was made
      possible through the use of mobile health. Trained FHP were able to reach out to
      the population. Electronic data capture facilitated efficient follow-up. The
      program was very cost-effective with screening completed under $1 per person.
      CLINICAL SIGNIFICANCE: In view of the high incidence of oral cancer in India, and
      the resource-constrained settings, mobile health paves the way for better access
      to specialist care for the rural population.

PMID- 30287716
TI  - Effect of Water Sorption and Solubility on Color Stability of Bulk-Fill Resin
      Composite.
AB  - AIM: The objective of this study is to compare the bulk-fill resin composite to a
      conventional one, as regards; water sorption, solubility, and their effect on
      color stability. MATERIALS AND METHODS: This study was conducted using two types
      of composites: Bulk-fill composite (Filtek Bulk-Fill) and nanohybrid composite
      for control (Filtek Z250 XT). Specimens were prepared using a ring mold, 10 from
      each material. Specimens were desiccated, then weighed in a digital balance until
      a stable mass was acquired. For water sorption test, specimens were immersed in
      distilled water and placed in a lightproof incubator at 37 +/- 1 degrees C and
      the mass was measured weekly for 8 weeks. For solubility test, specimens were
      desiccated again in the desiccator until a stable mass was achieved. A spectropho
      tometer was used to record the baseline color measurements prior to water
      immersion and weekly for 8 weeks. RESULTS: Bulk-fill composite showed higher
      water sorption value and lower water solubility values compared with that of the
      conventional one. No statistically significant difference was found for water
      sorption (p = 0.104) or water solubility (p = 0.098) between groups. The mean
      DeltaE was lower in bulk-fill than conventional composite, and results showed a
      statistically significant difference (p = 0.009). CONCLUSION: Bulk-fill resin
      composite yielded better color stability and similar water sorption and
      solubility values. CLINICAL SIGNIFICANCE: Bulk-fill resin composite can be used
      in esthetically concerned patients.

PMID- 30287717
TI  - Comparison of Frictional Resistance in Conventional Brackets with Different
      Stainless Steel Wires.
AB  - AIM: The aim of the study was to evaluate and compare static and kinetic friction
      of round (0.018") and rectangular (0.019 * 0.025") stainless steel (SS) wires of
      different brands with conventional preadjusted edgewise brackets. MATERIALS AND
      METHODS: Maxillary canine and two bicuspids of 0.022 * 0.028" slot sized MBT
      prescription (Gemini, 3M Unitek, Monrovia, California) brackets were chosen. The
      wires selected were 0.018" SS (3M Unitek); 0.018" Australian wire (AJ Wilcock,
      UK), and 0.019 * 0.025" SS (3M Unitek). The testing was done on Instron 3382. A
      total of 30 test combinations with three wires were repeated 10 times. The static
      and kinetic friction was recorded in Newton. The kinetic friction was also
      recorded in Newton at 3, 5, 7, and 9 mm of movement. One-way analysis of variance
      (ANOVA) and descriptive statistics were used for comparing the friction. To test
      the level of significance, multiple comparisons were used within wire in bracket
      by using post hoc test. RESULTS: Static friction was found to be greater than
      kinetic in all wires; 0.018" SS (3M) wire exhibited minimum static and kinetic
      friction; while 0.019 * 0.025" SS (3M) exhibited maximum static friction. Kinetic
      friction was similar in both 0.018" AJ Wilcock and 0.019 * 0.025" SS but greater
      than 0.018" SS (3M). CONCLUSION: Least static and kinetic friction was exhibited
      by 0.018" SS (3M). Kinetic friction was similar in both 0.018" AJ Wilcock and
      0.019 * 0.025" SS. CLINICAL SIGNIFICANCE: The study concluded that 0.018" SS (3M)
      is better for individual canine retraction than the other wires used in the study
      because it has the least frictional resistance; 0.019 * 0.025" SS (3M) is a
      better wire for canine retraction than 0.018" AJ Wilcock as we can have a three
      dimensional control over tooth movement. When torque control is not a prime
      requisite, then 0.018" SS (3M) can be used for retraction of incisors instead of
      0.018" AJ Wilcock in severely proclined incisor cases.

PMID- 30287718
TI  - Knowledge, Attitude, and Behavior toward Evidence-based Dentistry among Dental
      Professionals in Jodhpur Rajasthan, India.
AB  - INTRODUCTION: Rendering quality care to the patient, dentists needs to update
      their skills and knowledge with latest diagnostics and treatment modalities.
      Evidence-based dentistry can provide best-known treatments. AIM: To assess
      knowledge, attitude, and practice of oral healthcare professionals toward
      evidence-based dentistry among dental professionals. MATERIALS AND METHODS: A
      cross-sectional study was conducted for a period of 3 months from April 2017 to
      June 2017 in Jodhpur city, Rajasthan, India. The data were collected by using
      closed-ended questionnaires. A total of 240 study subjects participated in the
      survey, which include dental practitioners and dentists attached to the two
      private dental colleges in the Jodhpur. Chi-square test was used to determine
      significant difference among the three groups. RESULTS: Statistically significant
      difference among the three groups (academicians, practitioners, and academicians
      into dental practice) was found with regard to awareness of dentists about
      extracting journals, review publications, and databases relevant in carrying out
      evidence-based practice (EBP); 72.4% of academician felt lack of personal time
      was one of the major perceived barriers and about 50.7% of academician believe
      that learning skills of evidence-based dentistry helps them to utilize evidence
      based dentistry in daily practice. CONCLUSION: Majority of the oral health
      practitioners were not aware about the concept of evidence-based dentistry. The
      regulatory body of dental sciences in India should make some necessary changes in
      the dental curriculum to include the concept of evidence-based dentistry in
      detail. CLINICAL SIGNIFICANCE: To improve the clinical expertise of the dental
      professional, to aid dental professional to reach best decision regarding dental
      treatment of the patient, to improve patient safety, and to improve the success
      rate of dental treatments, evidence-based dentistry should be the integral part
      of everyday dental practice.

PMID- 30287719
TI  - The Efficiency of Three Irrigating Solutions after Surgical Removal of Impacted
      Mandibular Third Molars: A Cross-sectional Study.
AB  - AIM: The present study was conducted to assess the effect of irrigation with
      three different irrigants, namely normal saline, chlorhexidine, and povidone
      iodine on pain, alveolar osteitis, swelling, trismus, infection, and food
      impaction during surgical removal of impacted mandibular third molar. MATERIALS
      AND METHODS: Forty-eight patients, including 26 males and 22 females, fulfilling
      criteria for inclusion in this study were divided into three groups: group I
      where irrigant used was normal saline, group II as chlorhexidine, and group III
      as povidone iodine group. RESULTS: The pain was significantly more in groups I
      and III in 24 hours and 7th day as well. Alveolar osteitis was noted in groups
      III and I, nil in group II. The facial swelling measured in millimeters on 24
      hours and on 7th day was significantly higher in 24 hours in groups I and III
      than in group II. Trismus was significantly more in group I and group III than in
      group II (with p < 0.01) on 7th day. CONCLUSION: It is concluded that
      chlorhexidine is effective in reducing pain, alveolar osteitis, swelling, and
      trismus when used as an irrigant following surgical removal of impacted third
      molar. CLINICAL SIGNIFICANCE: Chlorhexidine as irrigating solution helps in
      reducing the postoperative consequences after third molar surgery. Further
      studies are required using large sample size.

PMID- 30287720
TI  - Nonsurgical Management and 2-year Follow-up by means of Cone Beam Computed
      Tomography of an Invasive Cervical Resorption in a Molar.
AB  - BACKGROUND: Invasive cervical resorption (ICR) is a relatively uncommon form of
      external tooth resorption, characterized by an invasive nature. It is usually
      painless and detection of lesions is often made incidentally. Three-dimensional
      imaging techniques, such as cone beam computed tomography (CBCT), are useful in
      the diagnosis and management of ICR as the true extent of the defect cannot
      always be estimated using conventional radiographs. AIM: The aim of this article
      is to report on the successful treatment of ICR in mandibular first molar by
      nonsurgical approach and follow-up by means of CBCT. CASE REPORT: An 18-year-old
      patient was referred with a complaint of unusual radiolucency in the mesial
      cervical area of tooth #19 with unknown etiology. Cone beam computed tomography
      was performed to assess the extent of the lesion in three spatial levels and
      diagnosis of Heithersay class III ICR was made. This case presented with ICR
      (Heithersay class III) on tooth #19. Nonsurgical root canal treatment and removal
      of the lesion from the coronal access was performed; the resorptive defect was
      filled with dual-cure, self-adhesive, resin-modified glass ionomer cement
      (RMGIC); 6-month follow-up X-ray film showed no changes at the lesion site and
      tooth was asymptomatic; 1-year follow-up X-ray film showed slight mesial bone
      loss and a probing depth of 3 mm; finally, 2-year follow-up CBCT images showed no
      recurrence and no further bone destruction at the lesion site. CONCLUSION: The
      intraoral radiographs revealed the resorptive changes in two dimensions;
      therefore, the actual extent and location of the lesions are not fully
      understood. On the contrary, CBCT is a very useful tool to achieve a proper
      diagnosis; it detects the extent of the defect more accurately and hence,
      improves the treatment outcomes of ICR. CLINICAL SIGNIFICANCE: The ICR is usually
      seen as a late complication to traumatic injuries of the teeth; it is essential,
      therefore, that the patients who were exposed to situations that can damage the
      integrity of periodontal tissue need to have careful periodic recalls and X-ray
      examinations.

PMID- 30287721
TI  - Oral Management of Steinert's Disease and Role of Anxiolysis.
AB  - BACKGROUND: Myotonic dystrophy type I (DM1) is a genetic autosomal dominant
      disorder; malignant hyperthermia is a possible complication. It may occur
      following administration of some halogenated general anesthetics, muscle
      relaxants, or surgical stress. AIM: The purpose of this case report is to
      evaluate the dental management of patients with Steinert's disease. CASE REPORT:
      The patient needed dental extraction. A locore-gional paraperiosteal anesthesia
      was performed using bupiva-caine without vasoconstrictor and sedation with
      nitrous oxide. The syndesmotomy of the elements 3.1, 4.1, and 4.2 was executed.
      The elements were dislocated through a straight lever and avulsed with an
      appropriate clamp. The socket was courted, washing with saline solution,
      inserting a fibrin sponge, and applying sutures (silk 3-0). CONCLUSION: Dental
      treatment of the patient with Steinert's dystrophy must be carried out under a
      hospital environment and the use of local anesthetic without vasoconstrictor and
      with use of nitrous oxide; anxiolysis is recommended. CLINICAL SIGNIFICANCE: This
      case report describes the precautions to perform oral surgery in patients with
      Steinert's disease and emphasizes the role of anxiolysis to avoid episodes of
      malignant hyperthermia.

PMID- 30287722
TI  - Korean Red Cross Hospital (1905-1907): Focused on its Establishment, Management
      and Abolition.
AB  - The Korean Empire, its state sovereignty threatened by the Empire of Japan,
      joined the Geneva Conventions in 1903 for the purpose of neutral diplomacy and
      established the imperial Korean Red Cross Hospital in 1905. This hospital was a
      result of the effort of the Korean Empire to seek a new medical system based on
      the Western medicine. However, after the Russo-Japanese War, Japan interfered
      straightforwardly in the domestic affairs of Korea and eventually abolished the
      Korean Red Cross Hospital in 1907 to create Daehan Hospital under Japanese
      colonial rule. With newly-found historical records, this study investigates the
      whole process of the Korean Red Cross Hospital, which has remained unknown so
      far, despite its importance. From the very beginning, the Korean Red Cross
      Hospital was under strong influence of the Empire of Japan. The site for the
      hospital was chosen by a Japanese army doctor, Junryo Yoshimoto, and the
      construction was supervised by Rokuro Katsumata, who also later on are involved
      in the construction of Daehan Hospital. Moreover, all the main positions for
      medical treatments were held by Japanese practitioners such as Goro Tatami and
      Kaneko Yano. Nevertheless, the Korean government had to shoulder the all
      operating costs. The office of the Korean Red Cross was relocated away from the
      Korean Red Cross Hospital, and the government of the Korean Empire was not
      willing to burden the expenses of the Hospital. Moreover, the list of employees
      of the Korean Red Cross and that of the Korean Red Cross Hospital were drawn up
      separately: the former is left only in Korea and the latter in Japan. These facts
      suggest that those two institutes were managed dualistically unlike any other
      nation, implying that this may have been a means to support the Daehan Hospital
      project. According to the statistics, health care services in the Korean Red
      Cross Hospital seems to have been carried out successfully. There had been an
      increase in the number of patients, and the ratio of female patients was
      relatively high (26.4%). Only Western medications were prescribed and surgical
      operations with anesthesia were performed routinely. The approach to Western
      medicine in Korea was changing during that period. The rise and fall of the
      Korean Red Cross Hospital represent the urgent situation of the Korean Empire as
      well as the imperialistic methodology of the Empire of Japan to use medicine as a
      tool for colonization. Although the transition process of medical policy by the
      Japanese Resident-General of Korea still remains to be fully elucidated, this
      paper contributes to a better understanding of the history of modern medicine in
      Korea.

PMID- 30287723
TI  - Yun Il-sun's Studies in Japan and Medical Research during the Colonial Period.
AB  - In this article, I looked at the life of Yun Il-sun, a representative medical
      scientist of modern Korea, and examined the following problems. First, I took
      note of the position of the Korean people in the academic system of the Japanese
      colonial empire and restored the life of Yun Il-sun as specifically as possible.
      Yun was educated among Japanese people from elementary school to university.
      Although he received the best education at Old System High School and Imperial
      University and grew to be a prominent medical scientist, he could not overcome
      his identity as a colonized. Yun Il-sun, who moved from Keijo Imperial University
      to Severance Union Medical College, involved in activities founding of the Korean
      Medical Association and the Korean Medical Journal. Second, I the meaning of
      'culture' to the intellectuals in the periphery. Old System High School and
      Imperial University where Yun Il-sun was educated were the hotbed of
      'culturalism.' Yun's college days were the heyday of Taisho Democracy, and
      students were attracted to Marxism, Christian poverty movement, Buddhist
      cultivation movement and so on. Yun sought to overcome the ideological of young
      people through the acquisition of 'culture.' The 'culture' emphasized by Yun had
      an enlightenment characteristic that emphasized education, but it also functioned
      as a'identity culture of educated elites.' Third, I used the concept of 'colonial
      academism' and examined the aspects and characteristics of the colonial-periphery
      academic field, focusing on medicine. Yun Il-sun was a Korean professor at the
      Keijo Imperial University. He founded an academic society and published an
      academic journal for Koreans. He attempted to reproduce scholarship by doctoral
      dissertations. At the same time, several facts show that he was also in the
      affected area of 'colonial academism': the fact that he was kicked out of the
      Keijo Imperial University, the fact that the Korean Medical Association and the
      Korean Medical Journal were banned by Governor General, the fact that his
      students asked for doctoral degrees from Kyoto Imperial University where he
      studied. Yun Il-sun crossed the limits of 'colonial academism' and acted as the
      agent of empire. This was made possible by the characteristics of the academic
      discipline of medicine, the environment of the Severance Union Medical College,
      and personal traits of superior ability and indifference to politics. I the
      postcolonial evolution of the 'colonial academism' and 'culturalism.' The mix of
      continuity and discontinuity from 'colonial academism' and the hybrid of Japanese
      academism and American academism, the Korean characteristics of 'postcolonial
      academism.' Yun tried to harmonize the American academism with the Japanese
      academism and the purity of academism. This effort was revealed as an emphasis on
      basic medicine and natural sciences. As combined with culturalism and
      indifference to politics, he was recognized as the symbol of ivory tower and
      academism.

PMID- 30287724
TI  - Beyond the Bifurcated Myth: The Medical Migration of Female Korean Nurses to West
      Germany in the 1970s.
AB  - This study investigates beyond the bifurcated myth of the medical migration of
      Korean women to Germany in the 1970s, which is known as the "German dispatchment"
      myth from the Korean perspective and the "development aid" discourse from that of
      the Germans, by focusing on the newly-released documents from the German Hospital
      Federation (Deutsche Krankenhausgesellschaft, DKG). The migration was essentially
      a transfer of labor from a weak to a strong state, and the disparity of state
      strength characterized the nature of the recruitment mechanism. Both Korea and
      Germany have romanticized the labor transfer and appropriated the collective
      experiences of migrants for their own political purposes. In this transnational
      business, the Korean Overseas Development Corporation (KODCO) and the DKG
      maintained exclusivity in the labor migration channel and were faithful to their
      own interests. The DKG, as a representative of the German healthcare industry,
      was concerned about being criticized for destroying the healthcare system of
      developing countries by stealing their skilled workforce. They, therefore, tried
      to influence publicity in Korea and Germany to persuade the people that the
      recruitment benefited both countries. However, the DKG was aware of the
      deceitfulness of its "development aid" discourse. The Korean government, which
      advanced the labor export for the sake of obtaining foreign currency,
      romanticized it as patriotism and used the term "German dispatchment." However,
      the incapacity and corruption of KODCO as an agency from the Korean perspective
      resulted in criticism regarding its recruitment program. The DKG complained that
      the selection of incapable personnel coupled with corruption was causing
      unforeseen financial damage to its member hospitals. Nevertheless, it officially
      defended its partner for the sake of its own interests, such as avoiding bad
      publicity and securing the sustainability of the recruitment program. The
      conflicts regarding nursing tasks and working conditions between Korean nurses
      and their German colleagues and employers captured in the documents of the DKG
      trace the origin of the issues in relation to cultural misunderstanding and
      pervasive racism. The disparity of state strength between the two countries
      resulted in the subaltern position of Korean female healthcare workers in the
      global labor market, and they tried to bring forth the best possible outcome
      while working in a foreign country in unfamiliar circumstances. However, the
      difficulties with female guest workers from Asia were generally credited to their
      inability to adhere to the German working style. This study contributes to the
      existing scholarship on this topic by filling the gaps. Historical research on
      the medical migration of Korean nurses and nurse-aides to West Germany has relied
      on limited historical sources. In 2013, the National Archives of Korea
      transferred official documents regarding these workers that were produced and
      archived by the DKG, which represented the interests of German healthcare
      institutions. Its documents on Korean nursing personnel provide supplementary
      information and display findings in different perspectives. They do not bring
      forth completely new findings that have never been researched before but are
      still valuable for delivering concrete evidence on the circumstances of that
      time, which were previously merely inferred.

PMID- 30287725
TI  - Examination of the Brain-Dead Organ Donor Management Process at a Spanish
      Hospital.
AB  - The number of donors and organs available has not increased at the same rate as
      the inclusion of new patients in the waiting lists. The aim of the present study
      was to analyze the quality of the detection process of potential brain-dead organ
      donors at the Hospital of Leon. For this, a cross-sectional prospective study was
      developed on a retrospective cohort of patients who were admitted or died by
      catastrophic brain damage with the potential for organs donation. Data were
      collected for six months using hospital records of admissions and exitus. For the
      statistical analysis, the free distribution software Epi Info 3.5.4 was employed.
      A total of 627 patients were studied: 550 were discharged and 77 died as
      potential donors. Of the potential donors, 65 died in asystole, but 60 of them
      had an absolute contraindication to donation and 20 died after limitation of life
      support therapy. Five cases with donor criteria in controlled asystole were
      detected. The analysis found that the detection process conformed to the
      regulatory framework stablished by the National Transplant Organization. However,
      population aging leads to a high rate of absolute contraindications among
      detected potential donors. The donation capacity of the hospital could therefore
      be increased with the implementation of a donor protocol in controlled asystole.

PMID- 30287727
TI  - Serum Carotenoids Reveal Poor Fruit and Vegetable Intake among Schoolchildren in
      Burkina Faso.
AB  - The health benefits of fruits and vegetables are well-documented. Those rich in
      provitamin A carotenoids are good sources of vitamin A. This cross-sectional
      study indirectly assessed fruit and vegetable intakes using serum carotenoids in
      193 schoolchildren aged 7 to 12 years in the Western part of Burkina Faso. The
      mean total serum carotenoid concentration was 0.23 +/- 0.29 umol/L, which
      included alpha- and beta-carotene, lutein, and beta-cryptoxanthin, and determined
      with serum retinol concentrations in a single analysis with high performance
      liquid chromatography. Serum retinol concentration was 0.80 +/- 0.35 umol/L with
      46% of children (n = 88) having low values <0.7 umol/L. Total serum carotene (the
      sum of alpha- and beta-carotene) concentration was 0.13 +/- 0.24 umol/L, well
      below the reference range of 0.9-3.7 umol carotene/L used to assess habitual
      intake of fruits and vegetables. Individual carotenoid concentrations were
      determined for alpha-carotene (0.01 +/- 0.05 umol/L), beta-carotene (0.17 +/-
      0.24 umol/L), beta-cryptoxanthin (0.07 +/- 0.06 umol/L), and lutein (0.06 +/-
      0.05 umol/L). These results confirm the previously measured high prevalence of
      low serum vitamin A concentrations and adds information about low serum
      carotenoids among schoolchildren suggesting that they have low intakes of
      provitamin A-rich fruits and vegetables.

PMID- 30287726
TI  - The Effect of Gluten-Free Diet on Health and the Gut Microbiota Cannot Be
      Extrapolated from One Population to Others.
AB  - Gluten-related disorders (GRD) affect millions of people worldwide and have been
      related to the composition and metabolism of the gut microbiota. These disorders
      present differently in each patient and the only treatment available is a strict
      life-long gluten-free diet (GFD). Several studies have investigated the effect of
      a GFD on the gut microbiota of patients afflicted with GRD as well as healthy
      people. The purpose of this review is to persuade the biomedical community to
      think that, while useful, the results from the effect of GFD on health and the
      gut microbiota cannot be extrapolated from one population to others. This
      argument is primarily based on the highly individualized pattern of gut microbial
      composition and metabolic activity in each person, the variability of the gut
      microbiota over time and the plethora of factors associated with this variation.
      In addition, there is wide variation in the composition, economic viability, and
      possible deleterious effects to health among different GFD, both within and among
      countries. Overall, this paper encourages the conception of more collaborative
      efforts to study local populations in an effort to reach biologically and
      medically useful conclusions that truly contribute to improve health in patients
      afflicted with GRD.

PMID- 30287728
TI  - Polish Validation of the SarQoL(r), a Quality of Life Questionnaire Specific to
      Sarcopenia.
AB  - Recently, SarQoL(r) (Sarcopenia and Quality of Life), a quality of life (QoL)
      questionnaire specific to sarcopenia, was successfully developed. For practical
      reasons, there is a great interest in validating this questionnaire in other
      populations. The aim of this cross-sectional study was to translate and adjust
      the SarQoL(r) into Polish and to standardize the validity of this method for the
      assessment of sarcopenic individuals in Poland with regard to psychometric
      properties. The English version was used for the translation process. A total of
      106 community-dwelling Caucasian subjects aged 73.3 +/- 5.94 years (65.1%
      females) were studied, with 60 participants being diagnosed sarcopenic. The
      translation and cross-cultural adaptation was carried out in five phases
      according to specific standard guidelines. There were no major linguistic issues
      in the translation process. The data confirmed a good discriminant validity,
      i.e., significantly lower scores for all domains (reduced global QoL in
      sarcopenic subjects compared to non-sarcopenic ones; 54.9 +/- 16.5 vs. 63.3 +/-
      17.1, p = 0.013), and high internal consistency (Cronbach's alpha coefficient was
      0.92). The significant correlation of the SarQoL(r) scores with those of other
      questionnaires (SF-36v2(r) Health Survey and EuroQoL-5-Dimension) that are
      supposed to have similar dimensions indicated the consistent construct validity
      of the SarQoL(r)-PL questionnaire. No floor/ceiling effects were found. An
      excellent agreement was found between the test and the re-test (intraclass
      coefficient correlation (ICC): 0.99). The first Polish version of the SarQoL(r)
      questionnaire is valid and consistent and therefore may be used with reliability
      for clinical and research purposes regarding QoL assessment of sarcopenic
      individuals. However, further research, in particular prospective studies, is
      needed to determine potential limitations and the suitability of the new tool for
      the Polish scenario and specificity.

PMID- 30287729
TI  - Effect of Resveratrol, a Dietary-Derived Polyphenol, on the Oxidative Stress and
      Polyol Pathway in the Lens of Rats with Streptozotocin-Induced Diabetes.
AB  - Resveratrol is found in grapes, apples, blueberries, mulberries, peanuts,
      pistachios, plums and red wine. Resveratrol has been shown to possess
      antioxidative activity and a variety of preventive effects in models of many
      diseases. The aim of the study was to investigate if this substance may
      counteract the oxidative stress and polyol pathway in the lens of diabetic rats.
      The study was conducted on the rats with streptozotocin-induced type 1 diabetes.
      After the administration of resveratrol (10 and 20 mg/kg po for 4 weeks), the
      oxidative stress markers in the lens were evaluated: activity of superoxide
      dismutase, catalase and glutathione peroxidase, as well as levels of total and
      soluble protein, level of glutathione, vitamin C, calcium, sulfhydryl group,
      advanced oxidation protein products, malonyldialdehyde, Total Oxidant Status and
      Total Antioxidant Reactivity. The obtained results indicate that the
      administration of resveratrol to the diabetic rats shows antioxidative
      properties. It is not a result of antiglycaemic activity but resveratrol probably
      directly affects the antioxidative system. Resveratrol did not affect the polyol
      pathway in the lens of diabetic rats. Our results may indirectly indicate
      benefits of consumption of foods as well as dietary supplements containing
      resveratrol in diminishing oxidative stress in lenses of individuals suffering
      from diabetes mellitus.

PMID- 30287731
TI  - LncRNAs in TGF-beta-Driven Tissue Fibrosis.
AB  - Transforming growth factor-beta (TGF-beta) is a crucial mediator in tissue
      fibrosis that promotes accumulation of extracellular matrix (ECM), myofibroblasts
      to epithelial-mesenchymal transition (EMT), endothelial-mesenchymal transition
      (EndoMT), and apoptosis via canonical and noncanonical signaling pathways. In the
      past decades, a number of microRNAs have been reported to participate in TGF-beta
      mediated tissue scarring; however, the roles of long noncoding RNAs (lncRNAs) in
      fibrogenesis remain largely unknown. Recently, emerging evidence has shown that
      lncRNAs are involved in the development of different diseases, including cancer,
      autoimmune diseases, cardiovascular diseases, and fibrotic diseases. In this
      review, we summarize the current updates of lncRNAs in TGF-beta1-driven tissue
      fibrosis and discuss their therapeutic potential for the treatment of chronic
      fibrotic diseases.

PMID- 30287730
TI  - delta-Tocotrienol, Isolated from Rice Bran, Exerts an Anti-Inflammatory Effect
      via MAPKs and PPARs Signaling Pathways in Lipopolysaccharide-Stimulated
      Macrophages.
AB  - delta-Tocotrienol, an important component of vitamin E, has been reported to
      possess some physiological functions, such as anticancer and anti-inflammation,
      however their molecular mechanisms are not clear. In this study, delta
      tocotrienol was isolated and purified from rice bran. The anti-inflammatory
      effect and mechanism of delta-tocotrienol against lipopolysaccharides (LPS)
      activated pro-inflammatory mediator expressions in RAW264.7 cells were
      investigated. Results showed that delta-tocotrienol significantly inhibited LPS
      stimulated nitric oxide (NO) and proinflammatory cytokine (TNF-alpha, IFN-gamma,
      IL-1beta and IL-6) production and blocked the phosphorylation of c-Jun N-terminal
      kinase (JNK) and extracellular regulated protein kinases 1/2 (ERK1/2). delta
      Tocotrienol repressed the transcriptional activations and translocations of
      nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1), which were
      closely related with downregulated cytokine expressions. Meanwhile, delta
      tocotrienol also affected the PPAR signal pathway and exerted an anti
      inflammatory effect. Taken together, our data showed that delta-tocotrienol
      inhibited inflammation via mitogen-activated protein kinase (MAPK) and peroxisome
      proliferator-activated receptor (PPAR) signalings in LPS-stimulated macrophages.

PMID- 30287732
TI  - Adherence to Gluten-Free Diet in Children with Celiac Disease.
AB  - Celiac disease (CD) can only be treated by rigorous life-long gluten-free diet
      (GFD). The study included 102 mothers and their CD children treated with GFD for
      at least two years. Frequency and cause of diet failure in children treated at
      present (54 children) and 10 years ago (48 children) were compared. Dietary
      adherence was evaluated serologically (tTG), while diet management difficulties
      were examined by means of a questionnaire. The study shows that one-third of
      patients fail to follow GFD, more often 10 years ago than now (40% vs. 26%; p <
      0.05), mainly children aged 13-18 (54% vs. 40% now; p < 0.05). Younger children
      (up to 12) are less likely to abandon the diet (27% vs. 8%; p < 0.05). In this
      age group non-intentional diet failure prevails, while teenagers interrupt their
      diet intentionally (45% vs. 33%; p = ns (small population of children in this
      groups)). Currently, the most common causes of teenage diet failure are the
      absence of symptoms after consuming a small amount of gluten and, even more
      often, troublesome diet administration. Previously, the absence of peer
      acceptance prevailed. With this study we found that: 1. In West Pomerania, every
      fourth CD child does not follow GFD. 2. For years, teenagers have failed to
      follow GFD due to the absence of symptoms after consuming small amounts of
      gluten. 3. The incidence of non-intentional failure to follow GFD has
      significantly decreased over years, which indicates better dietary care.

PMID- 30287734
TI  - Impact of Nutrition Education on the Compliance with Model Food Ration in 231
      Preschools, Poland: Results of Eating Healthy, Growing Healthy Program.
AB  - To ensure the adequate supply of nutrients, a model food ration (MFR) should be
      used for planning the menu. The purpose of the study was to determine the effects
      of the nutrition education program on the compliance with MFR in 231 preschools.
      The average supply of food products (per child/day) with reference to the MFR was
      examined on the baseline and 3 to 6 months after education on the basis of 10-day
      menus and daily inventory reports (4620 in total). According to the
      recommendations, preschool should implement 70-75% of the recommended daily
      intake standards. Examined menus had too high content of meat and meat products,
      whereas vegetables, milk and fermented milk beverages, cottage cheese and eggs
      were served in scarce. Education significantly reduced the amount of meat (47.7
      vs. 44.5 g), processed meat (16.2 vs. 14.4 g), sugar and sweets (15.9 vs. 14.4 g)
      and increased the amount of cereals, groats, rice (17.7 vs. 18.5 g), vegetables
      (164.3 vs. 170.8 g), milk and fermented milk beverages (200.3 vs. 209.5 g) but
      the compliance with the MFR remained poor. The evaluation of menus stressed the
      need for further modifying their composition. Education can positively affect the
      quality of nutrition; however, introduction of the legal nutritional regulations
      should be recommended.

PMID- 30287733
TI  - Achacha (Garcinia humilis) Rind Improves Cardiovascular Function in Rats with
      Diet-Induced Metabolic Syndrome.
AB  - Garcinia humilis is a fruit known as achachairu. It is native to South American
      countries such as Bolivia, Peru, and Brazil, but it is also cultivated as achacha
      in northern Australia. The aim of this study was to determine the phytochemicals
      in achacha rind and pulp and to investigate these components as potential
      treatments for the symptoms of metabolic syndrome. Both rind and pulp contain
      procyanidins and citric acid rather than hydroxycitric acid. Male Wistar rats (8
      9 weeks old) were fed with either high-carbohydrate, high-fat, or corn starch
      diets for 16 weeks. Intervention groups were fed with either diet supplemented
      with 1.5% G. humilis rind powder or 2.0% G. humilis pulp for the last 8 weeks of
      the protocol. Rats fed a high-carbohydrate, high-fat diet exhibited hypertension,
      dyslipidemia, central obesity, impaired glucose tolerance, and non-alcoholic
      fatty liver disease. G. humilis rind decreased systolic blood pressure, diastolic
      stiffness, left ventricular inflammatory cell infiltration, and collagen
      deposition in high-carbohydrate, high-fat diet-fed rats. However, there was no
      change in glucose tolerance, body weight, or body composition. Therefore, G.
      humilis rind, usually a food by-product, but not the edible pulp, showed
      potential cardioprotection with minimal metabolic changes in a rat model of diet
      induced metabolic syndrome.

PMID- 30287735
TI  - Effects of Astaxanthin on the Proliferation and Migration of Breast Cancer Cells
      In Vitro.
AB  - Astaxanthin (ASX) is a marine-based ketocarotenoid; an accessory pigment in
      plants in that it has many different potential functions. ASX is an antioxidant
      that is notably more potent than many other antioxidants. Antioxidants have anti
      inflammatory and oxidative stress-reducing properties to potentially reduce the
      incidence of cancer or inhibit the expansion of tumor cells. In this study, we
      tested the hypothesis that ASX would inhibit proliferation and migration of
      breast cancer cells in vitro. We found that application of ASX significantly
      reduced proliferation rates and inhibited breast cancer cell migration compared
      to control normal breast epithelial cells. Based on these results, further
      investigation of the effects of ASX on not only breast cancer cells, but other
      forms of tumor cells, should be carried out.

PMID- 30287736
TI  - Addictive Eating and Its Relation to Physical Activity and Sleep Behavior.
AB  - The obesity epidemic has led to the exploration of factors contributing to its
      etiology. Addictive eating, physical activity, and sleep behaviors have all been
      independently associated with obesity, and recent research suggests plausible
      interrelationships between food addiction, physical activity, and sleep. This
      study aims to investigate the relationship between food addiction with physical
      activity and sleep behavior. Australian adults were invited to complete an online
      survey which collected information including: demographics, food addiction
      symptoms, physical activity, sitting time and sleep behavior items. The sample
      comprised 1344 individuals with a mean age of 39.8 +/- 13.1 years (range 18-91),
      of which 75.7% were female. Twenty-two percent of the sample met the criteria for
      a diagnosis of food addiction as per the Yale Food Addiction Scale (YFAS 2.0)
      criteria, consisting of 0.7% with a "mild" addiction, 2.6% "moderate", and 18.9%
      classified as having a "severe" food addiction. Food-addicted individuals had
      significantly less physical activity (1.8 less occasions walking/week, 32 min
      less walking/week, 58 min less moderate to vigorous physical activity
      (MVPA)/week; p < 0.05), reported sitting for longer on weekends (83 min more on
      weekends/week; p < 0.001), and reported significantly more symptoms of poorer
      quality sleep (more likely to snore, more likely to have fallen asleep while
      driving, reported more days of daytime falling asleep; p < 0.05) compared to non
      food-addicted individuals. These differences were also observed in those with a
      "severe" food addiction classification. The present study suggests frequency and
      duration of physical activity, time spent sitting and sleep duration are
      associated with food addiction.

PMID- 30287738
TI  - Thermal Energy Storage and Mechanical Performance of Crude Glycerol Polyurethane
      Composite Foams Containing Phase Change Materials and Expandable Graphite.
AB  - The aim of this study was to enhance the thermal comfort properties of crude
      glycerol (CG) derived polyurethane foams (PUFs) using phase change materials
      (PCMs) (2.5-10.0% (wt/wt)) to contribute to the reduction of the use of non
      renewable resources and increase energy savings. The main challenge when adding
      PCM to PUFs is to combine the low conductivity of PUFs whilst taking advantage of
      the heat released/absorbed by PCMs to achieve efficient thermal regulation. The
      solution considered to overcome this limitation was to use expandable graphite
      (EG) (0.50-1.50% (wt/wt)). The results obtained show that the use of PCMs
      increased the heterogeneity of the foams cellular structure and that the
      incorporation of PCMs and EG increased the stiffness of the ensuing composite
      PUFs acting as filler-reinforcing materials. However, these fillers also caused a
      substantial increase of the thermal conductivity and density of the ensuing foams
      which limited their thermal energy storage. Therefore, numerical simulations were
      carried using a single layer panel and the thermal and physical properties
      measured to evaluate the behavior of a composite PUF panel with different
      compositions, and guide future formulations to attain more effective results in
      respect to temperature buffering and temperature peak delay.

PMID- 30287737
TI  - A Novel Antithrombotic Protease from Marine Worm Sipunculus Nudus.
AB  - Sipunculus nudus, an old marine species, has great potential for use as
      functional seafood due to its various bioactivities. Its potential antithrombotic
      activity pushed us to isolate the bio-active components bio-guided by tracking
      fibrinolytic activity. As a result, a novel protease named as SK (the kinase
      obtained from S. nudus) was obtained, which possessed a molecular weight of
      28,003.67 Da and 15 N-terminal amino acid sequences of PFPVPDPFVWDTSFQ. SK
      exerted inhibitory effects on thrombus formation through improving the
      coagulation system with dose-effect relationship within a certain range.
      Furthermore, in most cases SK got obviously better effect than that of urokinase.
      With the help of untargeted mass spectrometry-based metabolomics profiling,
      arachidonic acid, sphingolipid, and nicotinate and nicotinamide mechanism
      pathways were found to be important pathways. They revealed that the effect
      mechanism of SK on common carotid arterial thrombosis induced by FeCl3 was
      achieved by inhibiting vessel contraction, platelet aggregation, adhesion, and
      release, correcting endothelial cell dysfunction and retarding process of
      thrombus formation. This study demonstrated SK was a promising thrombolytic agent
      on the basis of its comprehensive activities on thrombosis, and it should get
      further exploitation and utilization.

PMID- 30287739
TI  - Non-Canonical Regulation of Type I Collagen through Promoter Binding of SOX2 and
      Its Contribution to Ameliorating Pulmonary Fibrosis by Butylidenephthalide.
AB  - Pulmonary fibrosis is a fatal respiratory disease that gradually leads to
      dyspnea, mainly accompanied by excessive collagen production in the fibroblast
      and myofibroblast through mechanisms such as abnormal alveolar epithelial cells
      remodeling and stimulation of the extracellular matrix (ECM). Our results show
      that a small molecule, butylidenephthalide (BP), reduces type I collagen (COL1)
      expression in Transforming Growth Factor beta (TGF-beta)-induced lung fibroblast
      without altering downstream pathways of TGF-beta, such as Smad phosphorylation.
      Treatment of BP also reduces the expression of transcription factor Sex
      Determining Region Y-box 2 (SOX2), and the ectopic expression of SOX2 overcomes
      the inhibitory actions of BP on COL1 expression. We also found that serial
      deletion of the SOX2 binding site on 3'COL1 promoter results in a marked
      reduction in luciferase activity. Moreover, chromatin immunoprecipitation, which
      was found on the SOX2 binding site of the COL1 promoter, decreases in BP-treated
      cells. In an in vivo study using a bleomycin-induced pulmonary fibrosis C57BL/6
      mice model, mice treated with BP displayed reduced lung fibrosis and collagen
      deposition, recovering in their pulmonary ventilation function. The reduction of
      SOX2 expression in BP-treated lung tissues is consistent with our findings in the
      fibroblast. This is the first report that reveals a non-canonical regulation of
      COL1 promoter via SOX2 binding, and contributes to the amelioration of pulmonary
      fibrosis by BP treatment.

PMID- 30287740
TI  - Welsh Onion Root (Allium fistulosum) Restores Ovarian Functions from Letrozole
      Induced-Polycystic Ovary Syndrome.
AB  - Polycystic ovarian syndrome (PCOS) is an endocrine, metabolic, and systemic
      disease. It is mainly characterized by hyperandrogenism, oligomenorrhea, and high
      levels of luteinizing hormone (LH). There is no obvious therapy for PCOS, so
      patients have received symptomatic therapy. Welsh onion (Allium fistulosum) is
      well-known in Asian countries for its usage in food ingredients and traditional
      medicines. It is also studied for its many effects. These include activation of
      immune responses, antihypertensive effects, and antioxidant effects. Using
      letrozole-induced PCOS rats, we focused on herbal therapy using extract of Allium
      fistulosum (AF; A. fistulosum) roots to improve ovarian functions. As a
      nonsteroidal aromatase inhibitor, letrozole blocks conversion of testosterone to
      estrogen and subsequently induces PCOS phenomenon. We divided six-week-old female
      rats into four groups, including control, letrozole, letrozole + AF extract, and
      temporary letrozole groups. In our study, treatment with AF extract shows a low
      plasma LH/FSH ratio, and reveals high estrogen levels, ovarian morphology,
      folliculogenesis-related genes, and aromatase expression under PCOS mimic
      conditions. We concluded that AF extract administration influenced aromatase
      production, enhanced the estrogen steroid synthesis, and consequently restored
      the estrogenic feedback mechanism on the pituitary-ovary system.

PMID- 30287741
TI  - Association of Coffee Consumption with Hearing and Tinnitus Based on a National
      Population-Based Survey.
AB  - Coffee is the one of the most common beverages worldwide and has received
      considerable attention for its beneficial health effects. However, the
      association of coffee with hearing and tinnitus has not been well studied. The
      aim of this study was to investigate the association of coffee with hearing and
      tinnitus based on a national population-based survey. We evaluated hearing and
      tinnitus data from the 2009-2012 Korean National Health and Nutrition Examination
      Survey and their relationship with a coffee consumption survey. All patients
      underwent a medical interview, physical examination, hearing test, tinnitus
      questionnaire and nutrition examination. Multivariable logistic regression models
      were used to examine the associations between coffee and hearing loss or
      tinnitus. We evaluated 13,448 participants (>=19 years) participants. The
      frequency of coffee consumption had a statistically significant inverse
      correlation with bilateral hearing loss in the 40-64 years age group. Daily
      coffee consumers had 50-70% less hearing loss than rare coffee consumers, which
      tended to be a dose-dependent relationship. In addition, the frequency of coffee
      consumption had an inverse correlation with tinnitus in the 19-64 years age group
      but its association was related with hearing. Brewed coffee had more of an
      association than instant or canned coffee in the 40-64 years age group. These
      results suggest a protective effect of coffee on hearing loss and tinnitus.

PMID- 30287743
TI  - Plant Essential Oils Enhance Diverse Pyrethroids against Multiple Strains of
      Mosquitoes and Inhibit Detoxification Enzyme Processes.
AB  - Mosquito-borne diseases account for the deaths of approximately 700,000 people
      annually throughout the world, with many more succumbing to the debilitating side
      effects associated with these etiologic disease agents. This is exacerbated in
      many countries where the lack of mosquito control and resources to prevent and
      treat mosquito-borne disease coincide. As populations of mosquito species grow
      more resistant to currently utilized control chemistries, the need for new and
      effective chemical means for vector control is more important than ever. Previous
      work revealed that plant essential oils enhance the toxicity of permethrin
      against multiple mosquito species that are of particular importance to public
      health. In this study, we screened permethrin and deltamethrin in combination
      with plant essential oils against a pyrethroid-susceptible and a pyrethroid
      resistant strain of both Aedes aegypti and Anopheles gambiae. A number of plant
      essential oils significantly enhanced the toxicity of pyrethroids equal to or
      better than piperonyl butoxide, a commonly used synthetic synergist, in all
      strains tested. Significant synergism of pyrethroids was also observed for
      specific combinations of plant essential oils and pyrethroids. Moreover, plant
      essential oils significantly inhibited both cytochrome P450 and glutathione S
      transferase activities, suggesting that the inhibition of detoxification
      contributes to the enhancement or synergism of plant essential oils for
      pyrethroids. This study highlights the potential of using diverse plant oils as
      insecticide additives to augment the efficacy of insecticidal formulations.

PMID- 30287742
TI  - Potential Role for Osteocalcin in the Development of Atherosclerosis and Blood
      Vessel Disease.
AB  - There is increasing evidence for the involvement of the skeleton in the
      regulation of atherosclerotic vascular disease. Osteocalcin, an osteoblast
      derived protein, exists in two forms, carboxylated and undercarboxylated
      osteocalcin. Undercarboxylated osteocalcin has been linked to the regulation of
      metabolic functions, including glucose and lipid metabolism. Features of
      atherosclerosis have been associated with circulating osteocalcin; however, this
      association is often conflicting and unclear. Therefore, the aim of this review
      is to examine the evidence for a role of osteocalcin in atherosclerosis
      development and progression, and in particular endothelial dysfunction and
      vascular calcification. The current literature suggests that undercarboxylated
      osteocalcin stimulates the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt)
      signaling pathway to upregulate nitric oxide and nuclear factor kappa beta (NF
      kbeta) in vascular cells, possibly protecting endothelial function and preventing
      atherogenesis. However, this effect may be mediated by metabolic factors, such as
      improvements in insulin signaling, rather than through a direct effect on the
      vasculature. Total osteocalcin is frequently associated with vascular
      calcification, an association that may occur as a result of vascular cells
      eliciting an osteogenic phenotype. Whether osteocalcin acts as a mediator or a
      marker of vascular calcification is currently unclear. As such, further studies
      that examine each form of osteocalcin are required to elucidate if it is a
      mediator of atherogenesis, and whether it functions independently of metabolic
      factors.

PMID- 30287744
TI  - River Management for Local Governments in China: From Public to Private.
AB  - The Public and Private Partnership (PPP) model has been used to provide public
      services and goods. In China, local governments are willing to use the PPP model
      in many public services, such as integrated river management (IRM) projects, due
      to ease fiscal budget and the improved access to technology from the private
      sector. However, there has not been any specific discussion in the literature for
      applying the PPP model to IRM projects. In this study, we find that the PPP model
      results in the non-standardization of IRM projects. Our research paper builds the
      PPP operation framework for IRM projects. Our findings suggest that while the
      environmental quality evaluation system created in contracts for government
      payment seems to be optimal for protecting the public interest, it actually
      strains the partnership between the two parties and so its implementation should
      be considered on a case by case basis. Since the history of IRM projects using
      the PPP model is short, the actual performances of these types of projects has
      not yet been demonstrated. Local governments should be cautious about adopting
      the PPP model for such projects, and private companies should be cautious about
      their involvement. Our research will garner more scholarly attention to the
      application of the PPP model in complex projects.

PMID- 30287746
TI  - Functionalized Gold Nanoparticles as Biosensors for Monitoring Cellular Uptake
      and Localization in Normal and Tumor Prostatic Cells.
AB  - In the present contribution the fabrication and characterization of
      functionalized gold nanospheres of uniform shape and controlled size is reported.
      These nano-objects are intended to be used as Surface Enhanced Raman Spectroscopy
      (SERS) sensors for in-vitro cellular uptake and localization. Thiophenol was used
      as molecular reporter and was bound to the Au surface by a chemisorption process
      in aqueous solution. The obtained colloidal solution was highly stable and no
      aggregation of the single nanospheres into larger clusters was observed. The
      nanoparticles were incubated in human prostatic cells with the aim of developing
      a robust, SERS-based method to differentiate normal and tumor cell lines. SERS
      imaging experiments showed that tumor cells uptake considerably larger amounts of
      nanoparticles in comparison to normal cells (up to 950% more); significant
      differences were also observed in the uptake kinetics. This largely different
      behaviour might be exploited in diagnostic and therapeutic applications.

PMID- 30287745
TI  - A Disposable Photovoltaic Patch Controlling Cellular Microenvironment for Wound
      Healing.
AB  - Electrical stimulation (ES) is known to affect the wound healing process by
      modulating skin cell behaviors. However, the conventional clinical devices that
      can generate ES for promoting wound healing require patient hospitalization due
      to large-scale of the extracorporeal devices. Herein, we introduce a disposable
      photovoltaic patch that can be applied to skin wound sites to control cellular
      microenvironment for promoting wound healing by generating ES. In vitro
      experiment results show that exogenous ES could enhance cell migration,
      proliferation, expression of extracellular matrix proteins, and myoblast
      differentiation of fibroblasts which are critical for wound healing. Our
      disposable photovoltaic patches were attached to the back of skin wound induced
      mice. Our patch successfully provided ES, generated by photovoltaic energy
      harvested from the organic solar cell under visible light illumination. In vivo
      experiment results show that the patch promoted cutaneous wound healing via
      enhanced host-inductive cell proliferation, cytokine secretion, and protein
      synthesis which is critical for wound healing process. Unlike the current
      treatments for wound healing that engage passive healing processes and often are
      unsuccessful, our wearable photovoltaic patch can stimulate regenerative
      activities of endogenous cells and actively contribute to the wound healing
      processes.

PMID- 30287748
TI  - Experimental Study on the Icing Dielectric Constant for the Capacitive Icing
      Sensor.
AB  - The capacitive method is considered to be a suitable icing-detection technology,
      but the lack of fundamental parameters restricts the development of icing
      detection sensors. In this paper, an artificial icing laboratory, a capacitive
      sensor, and some simulation conductors have been designed for obtaining the
      artificial icing samples. Subsequently, the same characteristic values of
      artificial icing have been measured by an LCR device, under a selected frequency.
      This research found that the value of the icing dielectric constant closely
      correlated with its density, internal sublayer, and the test temperature.
      Finally, a fitting formula has been presented for calculating the relative
      dielectric constant, which may provide some important reference value for the
      design of icing-detection sensors.

PMID- 30287747
TI  - Effect of Hydroxyapatite Formation on Titanium Surface with Bone Morphogenetic
      Protein-2 Loading through Electrochemical Deposition on MG-63 Cells.
AB  - Calcium phosphate ceramics used in dentistry and orthopedics are some of the most
      valuable biomaterials, owing to their excellent osteoconduction, osteoinduction,
      and osseointegration. Osteoconduction and osteoinduction are critical targets for
      bone regeneration, and osseointegration is essential for any dental
      implantations. In this study, a hydroxyapatite (HAp) hybrid coating layer with
      the sequential release of bone morphogenetic protein 2 (BMP-2) was deposited onto
      an etched titanium substrate by electrochemical deposition. The resulting release
      of BMP-2 from Ti-HAp was assessed by immersing samples in a simulated buffer
      fluid solution. Through coculture, human osteosarcoma cell proliferation and
      alkaline phosphatase activity were assessed. The characteristics and effect on
      cell proliferation of the hybrid coatings were investigated for their
      functionality through X-ray diffraction (XRD) and cell proliferation assays.
      Findings revealed that -0.8 V vs. Ag/AgCl (3 M KCl) exhibited the optimal HAp
      properties and a successfully coated HAp layer. XRD confirmed the crystallinity
      of the deposited HAp on the titanium surface. Ti-0.8 V Ti-HAp co-coating BMP
      sample exhibited the highest cell proliferation efficiency and was more favorable
      for cell growth. A successful biocompatible hybrid coating with optimized redox
      voltage enhanced the osseointegration process. The findings suggest that this
      technique could have promising clinical applications to enhance the healing times
      and success rates of dental implantation.

PMID- 30287749
TI  - Development of Eco-Friendly Polymer Foam Using Overcoat Technology of Deodorant.
AB  - Development of eco-friendly polymer foams is an urgent research topic because of
      the serious environmental pollution caused by trash heaps and the time-release of
      harmful gases. Polymer PVC foam using azodicarbonamide as a chemical foaming
      agent has been highly requested for further improvement due to the residual
      ammonia gas that continuously leaks out. Here, we demonstrate an effective and
      costless process for the reduction of releasing ammonia from PVC foams using the
      overcoat technology of deodorants. We have selected four candidate materials,
      gelite, zeolite, terra alba, and fumed silica as original materials for the
      deodorant of ammonia, and they showed an ammonia deodorization rate (ADR) of over
      80% without any treatment except the fumed silica. When we over-coated the UV
      curing agent mixed deodorants on the PVC foams (thickness ~300 um), the ADR of
      the terra alba and zeolite complex foams was remarkably higher than 90%, however,
      the specific gravity and chromaticity were not changed within 20%. This indicates
      that our developed process using deodorant layer for ammonia reduction has a high
      potential for the production of eco-friendly polymer foams.

PMID- 30287750
TI  - Fetal Renal Echogenicity Associated with Maternal Focal Segmental
      Glomerulosclerosis: The Effect of Transplacental Transmission of Permeability
      Factor suPAR.
AB  - We report a case of a pregnant woman with nephrotic syndrome due to biopsy-proven
      focal segmental glomerulosclerosis (FSGS) whose fetus developed echogenic kidneys
      and severe oligohydramnios by 27 weeks of gestation. Maternal treatment with
      prednisone resulted in normalization of the amniotic fluid indices and resolution
      of fetal renal echogenicity. The newborn was noted to have transient renal
      dysfunction and proteinuria, resolving by 6 weeks postpartum. The transplacental
      passage of permeability factors is postulated to have caused both the fetal and
      newborn renal presentation, with significantly elevated levels of soluble
      urokinase-type plasminogen activator receptor (suPAR) noted in the cord blood.
      This case documents the transplacental maternal-fetal transmission of suPAR,
      demonstrating the potential for maternal-fetal transmission of deleterious,
      disease-causing entities, and adds to the differential diagnosis of fetal
      echogenic kidneys. Further, this is the first documentation of a fetal response
      to maternal systemic therapy.

PMID- 30287752
TI  - Nanoscale Assembly of Copper Bearing-Sleeve via Cold-Welding: A Molecular
      Dynamics Study.
AB  - A bearing is an important component in contemporary machinery and equipment,
      whose main function is to support the mechanical rotator, reduce the friction
      coefficient during its movement, and guarantee the turning accuracy. However,
      assembly of a nanoscale bearing and sleeve is a challenging process for micro
      nano mechanical manufacturers. Hence, we show the cold-welding mechanism of a
      copper nanobearing-nanosleeve via molecular dynamic simulations. We demonstrate
      that it is feasible to assemble a bearing and sleeve at the nanoscale to form a
      stable mechanism. The effect of temperature in the range of 150 to 750 K is
      investigated. As the temperature rises, the mechanical strength and the weld
      stress of the welded structures markedly decrease, accompanied by the observation
      of increasing disorder magnitude. This comparison study is believed to facilitate
      future mechanical processing and structural nano-assembly of metallic elements
      for better mechanical performance.

PMID- 30287753
TI  - Selenium and Selenoproteins in Immune Mediated Thyroid Disorders.
AB  - Selenium is an essential micronutrient that is required for the synthesis of
      selenocysteine-containing selenoproteins, processing a wide range of health
      effects. It is known that the thyroid is one of the tissues that contain more
      selenium. The "selenostasis" maintenance seems to contribute to the prevention of
      immune mediated thyroid disorders. Prospective, observational studies,
      randomized, controlled studies evaluating selenium supplementation, and review
      articles that are available in Medline and PubMed have undergone scrutiny. The
      differences concerning methodology and results variability have been analyzed.
      Several authors support the idea of a potential efficacy of selenium (mainly
      selenomethionine) supplementation in reducing antithyroperoxidase antibody levels
      and improve thyroid ultrasound features. In mild Graves' orbitopathy, selenium
      supplementation has been associated with a decrease of the activity, as well as
      with quality of life improvement. Future research is necessary to clearly
      understand the selenium supplementation biologic effects while considering the
      basal selenium levels/biomarkers, selenoprotein gene polymorphisms that may be
      involved, underlying comorbidities and the major clinical outcomes.

PMID- 30287751
TI  - The Westward Journey of Alfalfa Leaf Curl Virus.
AB  - Alfalfa leaf curl virus (ALCV), which causes severe disease symptoms in alfalfa
      (Medicago sativa L.) and is transmitted by the widespread aphid species, Aphis
      craccivora Koch, has been found throughout the Mediterranean basin as well as in
      Iran and Argentina. Here we reconstruct the evolutionary history of ALCV and
      attempt to determine whether the recent discovery and widespread detection of
      ALCV is attributable either to past diagnostic biases or to the emergence and
      global spread of the virus over the past few years. One hundred and twenty ALCV
      complete genome sequences recovered from ten countries were analyzed and four
      ALCV genotypes (ALCV-A, ALCV-B, ALCV-C, and ALCV-D) were clearly distinguished.
      We further confirm that ALCV isolates are highly recombinogenic and that
      recombination has been a major determinant in the origins of the various
      genotypes. Collectively, the sequence data support the hypothesis that, of all
      the analyzed locations, ALCV likely emerged and diversified in the Middle East
      before spreading to the western Mediterranean basin and Argentina.

PMID- 30287755
TI  - Long-Term Biogas Production from Glycolate by Diverse and Highly Dynamic
      Communities.
AB  - Generating chemical energy carriers and bulk chemicals from solar energy by
      microbial metabolic capacities is a promising technology. In this long-term study
      of over 500 days, methane was produced by a microbial community that was fed by
      the mono-substrate glycolate, which was derived from engineered algae. The
      microbial community structure was measured on the single cell level using flow
      cytometry. Abiotic and operational reactor parameters were analyzed in parallel.
      The R-based tool flowCyBar facilitated visualization of community dynamics and
      indicated sub-communities involved in glycolate fermentation and methanogenesis.
      Cell sorting and amplicon sequencing of 16S rRNA and mcrA genes were used to
      identify the key organisms involved in the anaerobic conversion process. The
      microbial community allowed a constant fermentation, although it was sensitive to
      high glycolate concentrations in the feed. A linear correlation between glycolate
      loading rate and biogas amount was observed (R2 = 0.99) for glycolate loading
      rates up to 1.81 g L-1 day-1 with a maximum in biogas amount of 3635 mL day-1
      encompassing 45% methane. The cytometric diversity remained high during the whole
      cultivation period. The dominating bacterial genera were Syntrophobotulus,
      Clostridia genus B55_F, Aminobacterium, and Petrimonas. Methanogenesis was almost
      exclusively performed by the hydrogenotrophic genus Methanobacterium.

PMID- 30287754
TI  - DNA Methylation as a Biomarker of Treatment Response Variability in Serious
      Mental Illnesses: A Systematic Review Focused on Bipolar Disorder, Schizophrenia,
      and Major Depressive Disorder.
AB  - So far, genetic studies of treatment response in schizophrenia, bipolar disorder,
      and major depression have returned results with limited clinical utility. A gene
      * environment interplay has been proposed as a factor influencing not only
      pathophysiology but also the treatment response. Therefore, epigenetics has
      emerged as a major field of research to study the treatment of these three
      disorders. Among the epigenetic marks that can modify gene expression, DNA
      methylation is the best studied. We performed a systematic search (PubMed)
      following Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA guidelines for preclinical and clinical studies focused on genome-wide
      and gene-specific DNA methylation in the context of schizophrenia, bipolar
      disorders, and major depressive disorder. Out of the 112 studies initially
      identified, we selected 31 studies among them, with an emphasis on responses to
      the gold standard treatments in each disorder. Modulations of DNA methylation
      levels at specific CpG sites have been documented for all classes of treatments
      (antipsychotics, mood stabilizers, and antidepressants). The heterogeneity of the
      models and methodologies used complicate the interpretation of results. Although
      few studies in each disorder have assessed the potential of DNA methylation as
      biomarkers of treatment response, data support this hypothesis for
      antipsychotics, mood stabilizers and antidepressants.

PMID- 30287756
TI  - Synthesis and Characterization of Multi-Walled Carbon Nanotube/Graphene
      Nanoplatelet Hybrid Film for Flexible Strain Sensors.
AB  - Graphene nanoplatelet (GNP) and multi-walled carbon nanotube (MWCNT) hybrid films
      were prepared with the aid of surfactant Triton X-100 and sonication through a
      vacuum filtration process. The influence of GNP content ranging from 0 to 50 wt.%
      on the mechanical and electrical properties was investigated using the tensile
      test and Hall effect measurement, respectively. It showed that the tensile
      strength of the hybrid film is decreasing with the increase of the GNP content
      while the electrical conductivity exhibits an opposite trend. The effectiveness
      of the MWCNT/GNP hybrid film as a strain sensor is presented. The specimen is
      subjected to a flexural loading, and the electrical resistance measured by a two
      point probe method is found to be function of applied strain. Experimental
      results demonstrate that there are two different linear strain-sensing stages (0
      0.2% and 0.2-1%) in the resistance of the hybrid film with applied strain. The
      strain sensitivity is increasing with the increase of the GNP content. In
      addition, the repeatability and stability of the strain sensitivity of the hybrid
      film were conformed through the cyclic loading-unloading tests. The MWCNT/GNP
      hybrid film shows promising application for strain sensing.

PMID- 30287758
TI  - Reducing Stress Susceptibility of Broiler Chickens by Supplementing a Yeast
      Fermentation Product in the Feed or Drinking Water.
AB  - Reducing stress is an important goal in animal production. Previous research has
      demonstrated the ability of Original XPCTM to reduce the stress response of
      broilers during heat stress. Three trials were conducted to evaluate the effects
      of adding Original XPCTM to the feed or AviCareTM to the water on stress
      susceptibility of broiler chickens. Treatments included: control nonstressed
      (CNS), control stressed (CS), stressed with Original XPCTM (1.25 kg/metric ton
      feed, 0-42 days; XPC), and stressed with AviCareTM (160 mL/100 L drinking water,
      0-42 days; AVI). All stressed treatments received the following stressors: live
      coccidiosis vaccination (day 1), reared on reused litter (days 0-42), and heat
      stress with feed/water withdrawal (12 h on day 18). Plasma corticosterone and
      heterophil/lymphocyte (H/L) ratio were determined from 60 birds/T on day 19, and
      24 birds/T on day 41. Physical asymmetry was determined using bilateral bone
      measurements from 60 birds/T on day 41. Birds provided XPC or AVI had lower
      corticosterone and H/L ratios than CS (p < 0.05) on day 19 and lower
      corticosterone, H/L ratios, and asymmetry scores than both CNS and CS on day 41
      (p < 0.05) in all three trials. Supplementing XPC or AVI improved broiler welfare
      measured by reduced stress indicators after acute heat stress or normal rearing
      stress in all trials.

PMID- 30287759
TI  - Effect of Long-Term High Temperature Oxidation on the Coking Behavior of Ni-Cr
      Superalloys.
AB  - The service time of an industrial cracker is strongly dependent on the long-term
      coking behavior and microstructure stability of the reactor coil alloy. Super
      alloys are known to withstand temperatures up to even 1400 K. In this work,
      several commercially available alloys have been first exposed to a long term
      oxidation at 1423 K for 500 h, so-called metallurgic aging. Subsequently, their
      coking behavior was evaluated in situ in a thermogravimetric setup under ethane
      steam cracking conditions (Tgasphase = 1173 K, Ptot = 0.1 MPa, XC2H6 = 70%,
      continuous addition of 41 ppmw S/HC of DMDS, dilution delta = 0.33 kgH2O/kgHC)
      and compared with their unaged coking behavior. The tested samples were also
      examined using scanning electron microscopy and energy diffractive X-ray for
      surface and cross-section analysis. The alloys characterized by increased Cr-Ni
      content or the addition of Al showed improved stability against bulk oxidation
      and anti-coking behavior after application of metallurgic aging due to the
      formation of more stable oxides on the top surface.

PMID- 30287757
TI  - The Anticancer Properties of Cordycepin and Their Underlying Mechanisms.
AB  - Cordyceps is a genus of ascomycete fungi that has been used for traditional
      herbal remedies. It contains various bioactive ingredients including cordycepin.
      Cordycepin, also known as 3-deoxyadenosine, is a major compound and has been
      suggested to have anticancer potential. The treatment of various cancer cells
      with cordycepin in effectively induces cell death and retards their cancerous
      properties. However, the underlying mechanism is not fully understood. Recent
      evidence has shed light on the molecular pathways involving cysteine-aspartic
      proteases (caspases), mitogen-activated protein kinases (MAPKs), and glycogen
      synthase kinase 3 beta (GSK-3beta). Furthermore, the pathways are mediated by
      putative receptors, such as adenosine receptors (ADORAs), death receptors (DRs),
      and the epidermal growth factor receptor (EGFR). This review provides the
      molecular mechanisms by which cordycepin functions as a singular or combinational
      anticancer therapeutic agent.

PMID- 30287760
TI  - Genistein Loaded Nanofibers Protect Spinal Cord Tissue Following Experimental
      Injury in Rats.
AB  - Innovative drug-delivery systems offer a unique approach to effectively provide
      therapeutic drug dose over the needed time to achieve better tissue protection
      and enhanced recovery. The hypothesis of the current study was to test the
      antioxidant and anti-inflammatory effects of genistein and nanofibers on the
      spinal cord tissue following experimental spinal cord injury (SCI). Rats were
      treated post SCI with genistein that is loaded on chitosan/polyvinyl alcohol
      (CS/PVA) nanofibers as an implantable drug-delivery system. SCI caused marked
      oxidative damage and inflammation, as is evident by the reduction in the super
      oxide dismutase (SOD) activity and the level of interleukin-10 (IL-10) in injured
      spinal cord tissue, as well as the significant increase in the levels of nitric
      oxide (NO), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-alpha).
      Treatment of rats post SCI with genistein and CS/PVA nanofibers improved most of
      the above-mentioned biochemical parameters and shifted them toward the control
      group values. Genistein induced an increase in the activity of SOD and the level
      of IL-10, while causing a decrease in NO, MDA, and TNF-alpha in injured spinal
      cord tissue. Genistein and CS/PVA nanofibers provide a novel combination for
      treating inflammatory nervous tissue conditions, especially when combined as an
      implantable drug-delivery system.

PMID- 30287761
TI  - The Effect of Statin Added to Systemic Anticancer Therapy: A Meta-Analysis of
      Randomized, Controlled Trials.
AB  - Preclinical studies have demonstrated that statins have anticancer properties and
      act in an additive or synergistic way when combined with anticancer therapy. We
      conducted this meta-analysis of randomized, controlled phase II or III trials to
      evaluate the effect of statins added to systemic anticancer therapy in patients
      with solid cancer. A systematic literature search was performed to identify all
      randomized trials that were designed to investigate the effect of statins in
      patients with cancer using PubMed, EMBASE, Google Scholar, and Web of Science (up
      to August 2018). From eight randomized controlled trials, 1760 patients were
      included in the pooled analyses of odds ratios (ORs) with 95% confidence
      intervals (CIs) for grade 3-5 adverse events (AEs) and overall response rate
      (ORR) and hazard ratios (HRs) with 95% CIs for progression-free survival (PFS)
      and overall survival (OS). The addition of statin to anticancer agents did not
      significantly increase the incidence of grade 3-5 AEs (OR = 1.03, 95% CI: 0.81
      1.29, p = 0.78). However, the combination of statin and anticancer agents did not
      improve ORR (OR = 0.96, 95% CI: 0.77-1.20, p = 0.72) compared with that of
      anticancer therapy alone. In addition, statins added to systemic anticancer
      therapy failed to prolong PFS (HR = 0.99, 95% CI: 0.90-1.10, p = 0.92) and OS (HR
      = 0.91, 95% CI: 0.76-1.11, p = 0.52). In conclusion, this meta-analysis of
      randomized controlled trials does not support clinical benefits of statins added
      to systemic anticancer therapy in patients with solid cancer.

PMID- 30287762
TI  - Impact of Mixed Equine Influenza Vaccination on Correlate of Protection in
      Horses.
AB  - To evaluate the humoral immune response to mixed Equine Influenza vaccination, a
      common practice in the field, an experimental study was carried out on 42
      unvaccinated thoroughbred weanling foals divided into six groups of seven. Three
      groups were vaccinated using a non-mixed protocol (Equilis(r) Prequenza-Te,
      Proteqflu-Te(r) or Calvenza-03(r)) and three other groups were vaccinated using a
      mix of the three vaccines mentioned previously. Each weanling underwent a primary
      EI vaccination schedule composed of two primary immunisations (V1 and V2) four
      weeks apart followed by a third boost immunisation (V3) six months later.
      Antibody responses were monitored until one-year post-V3 by single radial
      haemolysis (SRH). The results showed similar antibody responses for all groups
      using mixed EI vaccination and the group exclusively vaccinated with Equilis(r)
      Prequenza-TE, which were significantly higher than the other two groups
      vaccinated with Proteqflu-TE(r) and Calvenza-03(r). All weanlings (100%) failed
      to seroconvert after V1 and 21% (9/42) still had low or no SRH antibody titres
      two weeks post-V2. All weanlings had seroconverted and exceeded the clinical
      protection threshold one month after V3. The poor response to vaccination was
      primarily observed in groups exclusively vaccinated with Proteqflu-Te(r) and
      Calvenza-03(r). A large window of susceptibility (3-4.5-month duration) usually
      called immunity gap was observed after V2 and prior to V3 for all groups. The SRH
      antibody level was maintained above the clinical protection threshold for three
      months post-V3 for the groups exclusively vaccinated with Proteqflu-Te(r) and
      Calvenza-03(r), and six months to one year for groups using mixed EI vaccination
      or exclusively vaccinated with Equilis(r) Prequenza-Te. This study demonstrates
      for the first time that the mix of EI vaccines during the primary vaccination
      schedule has no detrimental impact on the correlate of protection against EIV
      infection.

PMID- 30287764
TI  - Anthropometric Status among 6-9-Year-Old School Children in Rural Areas in Hai
      Phong City, Vietnam.
AB  - A double burden of malnutrition in Vietnamese children has emerged as a key
      challenge: childhood undernutrition remains a public health concern while
      childhood overweight/obesity has gradually increased. This study aimed to (1)
      estimate the prevalence of undernutrition and overnutrition among 6-9-year-old
      primary school children in rural areas of Vietnam, and (2) identify
      sociodemographic factors associated with undernutrition and overnutrition in this
      population. A cross-sectional survey was conducted in October 2016 in 2334
      children from eight primary schools in rural areas in Hai Phong City, Vietnam.
      Anthropometric and demographic data were collected. The prevalence of
      underweight, stunting, wasting, and anthropometric failure was 8.0%, 5.1%, 5.3%,
      and 11.9%, respectively. Up to 22.1% of children were affected by
      overweight/obesity, and 31.0% by abdominal overweight/obesity. Low maternal
      education was associated with higher odds of underweight and anthropometric
      failure, whereas overweight/obesity or abdominal overweight/obesity were more
      likely in boys and children of mothers with a high education level. This study
      provides evidence for a double burden of diseases among primary school children
      in rural areas in Hai Phong City. Future interventions for the prevention and
      control of childhood undernutrition and overweight/obesity should take into
      account child sex and maternal education level.

PMID- 30287765
TI  - Spin-Coated CH3NH3PbBr3 Film Consisting of Micron-Scale Single Crystals Assisted
      with a Benzophenone Crystallizing Agent and Its Application in Perovskite Light
      Emitting Diodes.
AB  - Owing to the superior properties of optical and electronic properties, perovskite
      single crystals have been in high demand recently. However, the growth of large
      sized single crystals requires several processing steps and a long growth time,
      which engenders great difficulties in device integration. Herein, benzophenone
      (BP) was firstly introduced as a crystallizing agent to facilitate the
      construction of a high-quality CH3NH3PbBr3 (MAPbBr3) film consisting of micron
      scale single crystals in a one-step spin-coating method. We studied the influence
      of the BP concentration upon the size and shape of the micron-scale single
      crystals. Moreover, due to the enhanced morphology of the MAPbBr3 film with low
      defect micron-scale single crystals, perovskite light-emitting diodes (PeLEDs)
      have been demonstrated with a maximum luminance of 1057.6 cd/m2 and a turn-on
      voltage as low as 2.25 V. This approach not only proposes a concise and highly
      repeatable method for the formation of micron-scale perovskite single crystals,
      but also paves a way for the realization of efficient PeLEDs.

PMID- 30287766
TI  - Effect of Educational Interventions on Understanding and Use of Nutrition Labels:
      A Systematic Review.
AB  - The potential for nutrition labels to impact on population health is dependent on
      consumer ability to understand and use this information. Consumer understanding
      of this information varies across sociodemographic groups and with different
      label design formats. Labeling legislation requires consumer education on how to
      use nutrition labels, and recent mandatory changes to the Nutrition Facts Panel
      (NFP) are underway to improve comprehensibility. This review aimed to evaluate if
      educational programs can improve understanding and use of nutrition labels.
      Database searches were performed to identify interventions which delivered
      education on nutrition labels with outcomes measuring aspects of comprehension or
      use. A total of 17 studies were selected for review, including nine randomized
      and eight cohort studies. The majority of studies were conducted in the United
      States Study participants included school aged children, older adults, and those
      with diabetes within a range of intervention types involving taught sessions or
      web-based education. Whilst outcome measures were heterogenous, all studies
      reported a statistically significant improvement in one or more outcomes of
      participant understanding or use of nutrition labels. Aspects such as general
      nutrition knowledge, health literacy, and program delivery format warrant
      attention in future research. Education which optimizes comprehension and use of
      nutrition labels may have the potential to improve the impact of this information
      on dietary health.

PMID- 30287768
TI  - Reliability of X7R Multilayer Ceramic Capacitors During High Accelerated Life
      Testing (HALT).
AB  - Multilayer ceramic capacitors (MLCC) are essential components for determining the
      reliability of electronic components in terms of time to failure. It is known
      that the reliability of MLCCs depends on their composition, processing, and
      operating conditions. In this present work, we analyzed the lifetime of three
      similar X7R type MLCCs based on BaTiO3 by conducting High Accelerated Life Tests
      (HALT) at temperatures up to 200  degrees C at 400 V and 600 V. The results were
      adjusted to an Arrhenius equation, which is a function of the activation energy
      (Ea) and a voltage stress exponent (n), in order to predict their time to
      failure. The values of Ea are in the range of 1-1.45 eV, which has been reported
      for the thermal failure and dielectric wear out of BaTiO3-based dielectric
      capacitors. The stress voltage exponent value was in the range of 4-5. Although
      the Ea can be associated with a failure mechanism, n only gives an indication of
      the effect of voltage in the tests. It was possible to associate those values
      with each type of tested MLCC so that their expected life could be estimated in
      the range of 400-600 V.

PMID- 30287763
TI  - Role of Extracellular Matrix in Development and Cancer Progression.
AB  - The immense diversity of extracellular matrix (ECM) proteins confers distinct
      biochemical and biophysical properties that influence cell phenotype. The ECM is
      highly dynamic as it is constantly deposited, remodelled, and degraded during
      development until maturity to maintain tissue homeostasis. The ECM's composition
      and organization are spatiotemporally regulated to control cell behaviour and
      differentiation, but dysregulation of ECM dynamics leads to the development of
      diseases such as cancer. The chemical cues presented by the ECM have been
      appreciated as key drivers for both development and cancer progression. However,
      the mechanical forces present due to the ECM have been largely ignored but
      recently recognized to play critical roles in disease progression and malignant
      cell behaviour. Here, we review the ways in which biophysical forces of the
      microenvironment influence biochemical regulation and cell phenotype during key
      stages of human development and cancer progression.

PMID- 30287767
TI  - Chaperones, Canalization, and Evolution of Animal Forms.
AB  - Over half a century ago, British developmental biologist Conrad Hal Waddington
      proposed the idea of canalization, that is, homeostasis in development. Since the
      breakthrough that was made by Rutherford and Lindquist (1998), who proposed a
      role of Hsp90 in developmental buffering, chaperones have gained much attention
      in the study of canalization. However, recent studies have revealed that a number
      of other molecules are also potentially involved in canalization. Here, I
      introduce the emerging role of DnaJ chaperones in canalization. I also discuss
      how the expression levels of such buffering molecules can be altered, thereby
      altering organismal development. Since developmental robustness is maternally
      inherited in various organisms, I propose that dynamic bet hedging, an increase
      in within-clutch variation in offspring phenotypes that is caused by
      unpredictable environmental challenges to the mothers, plays a key role in
      altering the expression levels of buffering molecules. Investigating dynamic bet
      hedging at the molecular level and how it impacts upon morphological phenotypes
      will help our understanding of the molecular mechanisms of canalization and
      evolutionary processes.

PMID- 30287769
TI  - Analysis of Heavy Metal Sources in the Soil of Riverbanks Across an Urbanization
      Gradient.
AB  - Regional soil quality issues arising from rapid urbanization have received
      extensive attention. The riverbank that runs through a city is representative of
      urbanization gradient transformation. Thirty soil samples in the Yangtze River
      Delta urban agglomeration were collected and analyzed for the concentrations of
      seven analytes. Correlation, principle component analysis, cluster analysis and
      GeoDetector models suggested that the four groups (Cr-Ni-Cu, Cu-Zn-As-Sb, Cd and
      Pb) shared the same sources in the core urban region; five groups (Cr-Ni-Cu-Zn,
      As, Cd, Sb and Pb) in the suburbs and three groups (Cr-Ni, Cu-Zn-Cd-Sb-Pb and As)
      in the exurbs. GeoDetector methods not only validated the results of the three
      other methods, but also provided more possible impact factors. Besides the direct
      influences, the interaction effects among factors were quantified. Interactive
      combination with strong nonlinear increment changed from between-two-weak factors
      in the central region to between-strong-and-weak factors in the suburbs. In the
      exurbs, the stronger interaction effects were observed between strong and weak
      factors. Therefore, the GeoDetector model, which provided more detailed
      information of artificial sources could be used as a tool for identifying the
      potential factors of toxic elements and offering scientific basis for the
      development of subsequent pollution reduction strategies.

PMID- 30287770
TI  - The Characterization of Immunoprotection Induced by a cDNA Clone Derived from the
      Attenuated Taiwan Porcine Epidemic Diarrhea Virus Pintung 52 Strain.
AB  - The porcine epidemic diarrhea virus (PEDV) poses a great threat to the global
      swine industries and the unreliable protection induced by the currently available
      vaccines remains a major challenge. We previously generated a genogroup 2b (G2b)
      PEDV Taiwan Pintung 52 (PEDVPT) strain, PEDVPT-P96, and determined its promising
      host immune response against the virulent PEDVPT-P5 strain. To study the
      attenuation determinants of PEDVPT-P96 and establish a PEDVPT-P96-based
      recombinant vector as a vaccine platform for further antigenicity modification,
      iPEDVPT-P96, a full-length cDNA clone of PEDVPT-P96, was established. Comparing
      to the parental PEDVPT-P96 virus, the iPEDVPT-P96 virus showed efficient
      replication kinetics with a delayed decline of viral load and similar but much
      more uniform plaque sizes in Vero cells. In the 5-week-old piglet model, fecal
      viral shedding was observed in the PEDVPT-P96-inoculated piglets, whereas those
      inoculated with iPEDVPT-P96 showed neither detectable fecal viral shedding nor
      PEDV-associated clinical signs. Moreover, inoculation with iPEDVPT-P96 elicited
      comparable levels of anti-PEDV specific plasma IgG and fecal/salivary IgA,
      neutralizing antibody titers, and similar but less effective immunoprotection
      against the virulent PEDVPT-P5 challenge compared to the parental PEDVPT-P96. In
      the present study, an infectious cDNA clone of an attenuated G2b PEDV strain was
      successfully generated for the first time, and the in vitro and in vivo data
      indicate that iPEDVPT-P96 is further attenuated but remains immunogenic compared
      to its parental PEDVPT-P96 viral stock. The successful development of the iPEDVPT
      P96 cDNA clone could allow for the manipulation of the viral genome to study
      viral pathogenesis and facilitate the rapid development of effective vaccines.

PMID- 30287771
TI  - Demographics Regarding Belief in Non-Human Animal Sentience and Emotional Empathy
      with Animals: A Pilot Study among Attendees of an Animal Welfare Symposium.
AB  - Attitudes to animals are linked to beliefs about their ability to experience pain
      and suffering, their cognition, and their sentience. Education and awareness
      raising play a pivotal role in increasing society's consideration of non-human
      animal welfare. The current pilot study explores the attitudes towards animal
      welfare among a unique population of people who attended an animal welfare
      symposium at the University of Sydney. It involved administration of a validated
      questionnaire that assessed attitudes to animals; specifically exploring
      participants' (n = 41) beliefs about the sentience of animals and their emotional
      empathy with animals. The resultant data revealed significant associations
      between participants' beliefs in animal sentience and their demographic variables
      (age, sex and occupation). Female attendees showed stronger beliefs in sentience
      than male attendees did. Concerning sentience in cows, pigs and cats, older
      attendees showed stronger beliefs than younger people in sentience relating to
      hunger and pain. Also, with regard to questions about sentience in dogs, older
      attendees showed stronger beliefs than younger people in pain-related sentience
      in dogs. When exploring emotional empathy with animals, the participants'
      statements could be assigned to three clusters characterised by the internal
      emotional lives of animals and the treatment of animals by humans (Cluster 1),
      human interactions with animals (Cluster 2) and the keeping of companion and zoo
      animals (Cluster 3). To the authors' knowledge, this pilot study is the first of
      its kind to investigate the attitudes towards animal welfare of an important
      group of people who work, study or have a special interest within the animal care
      and welfare domain.

PMID- 30287773
TI  - Advances in Magnetic Nanoparticles-Supported Palladium Complexes for Coupling
      Reactions.
AB  - Carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds that form via transition
      metal-catalyzed processes have been extensively used in the organic synthesis and
      preparation of natural products and important compounds such as heterocycles,
      biologically active molecules, and dendrimers. Among the most significant
      catalysts, magnetic nanoparticles-supported palladium complexes are very
      effective, versatile, and heterogeneous catalysts for a wide range of C-C and C-X
      coupling reactions due to their reusability, thermal stability, and excellent
      catalytic performance. In this review, recent advances to develop magnetic
      nanoparticles supported palladium complexes, including their preparation,
      characterization, catalytic application, and reusability in the formation of both
      C-C and C-X bonds, by authors such as Sonogashira, Heck, Suzuki-Miyaura, and
      Stille, and a few examples concerning N-arylation, S-arylation, and Csp2-P
      coupling reactions are discussed.

PMID- 30287774
TI  - A Lightweight Cipher Based on Salsa20 for Resource-Constrained IoT Devices.
AB  - The Internet of Things (IoT) paradigm envisions a world where everyday things
      interchange information between each other in a way that allows users to make
      smarter decisions in a given context. Even though IoT has many advantages, its
      characteristics make it very vulnerable to security attacks. Ciphers are a
      security primitive that can prevent some of the attacks; however, the constrained
      computing and energy resources of IoT devices impede them from implementing
      current ciphers. This article presents the stream cipher Generador de Bits Pseudo
      Aleatorios (GBPA) based on Salsa20 cipher, which is part of the eSTREAM project,
      but designed for resource-constrained IoT devices of Class 0. GBPA has lower
      program and data memory requirements compared with Salsa20 and lightweight
      ciphers. These properties allow low-cost resource-constrained IoT devices, 29.5%
      of the embedded systems in the market, to be able to implement a security service
      that they are currently incapable of, to preserve the user's data privacy and
      protect the system from attacks that could damage it. For the evaluation of its
      output, three statistical test suites were used: NIST Statistical Test Suite
      (STS), DIEHARD and EACirc, with good results. The GBPA cipher provides security
      without having a negative impact on the computing resources of IoT devices.

PMID- 30287772
TI  - Nanoporous Anodic Alumina Photonic Crystals for Optical Chemo- and Biosensing:
      Fundamentals, Advances, and Perspectives.
AB  - Optical sensors are a class of devices that enable the identification and/or
      quantification of analyte molecules across multiple fields and disciplines such
      as environmental protection, medical diagnosis, security, food technology,
      biotechnology, and animal welfare. Nanoporous photonic crystal (PC) structures
      provide excellent platforms to develop such systems for a plethora of
      applications since these engineered materials enable precise and versatile
      control of light-matter interactions at the nanoscale. Nanoporous PCs provide
      both high sensitivity to monitor in real-time molecular binding events and a
      nanoporous matrix for selective immobilization of molecules of interest over
      increased surface areas. Nanoporous anodic alumina (NAA), a nanomaterial long
      envisaged as a PC, is an outstanding platform material to develop optical sensing
      systems in combination with multiple photonic technologies. Nanoporous anodic
      alumina photonic crystals (NAA-PCs) provide a versatile nanoporous structure that
      can be engineered in a multidimensional fashion to create unique PC sensing
      platforms such as Fabry-Perot interferometers, distributed Bragg reflectors,
      gradient-index filters, optical microcavities, and others. The effective medium
      of NAA-PCs undergoes changes upon interactions with analyte molecules. These
      changes modify the NAA-PCs' spectral fingerprints, which can be readily
      quantified to develop different sensing systems. This review introduces the
      fundamental development of NAA-PCs, compiling the most significant advances in
      the use of these optical materials for chemo- and biosensing applications, with a
      final prospective outlook about this exciting and dynamic field.

PMID- 30287775
TI  - Evaluation of A Concentrated Preterm Formula as a Liquid Human Milk Fortifier in
      Preterm Babies at Increased Risk of Feed Intolerance.
AB  - There are concerns around safety and tolerance of powder human milk fortifiers to
      optimize nutrition in preterm infants. The purpose of this study was to evaluate
      the tolerance and safety of a concentrated preterm formula (CPF) as a liquid
      human milk fortifier (HMF) for premature infants at increased risk of feeding
      intolerance. We prospectively enrolled preterm infants over an 18-month period,
      for whom a clinical decision had been made to add CPF to human milk due to
      concerns regarding tolerance of powder HMF. Data on feed tolerance,
      anthropometry, and serum biochemistry values were recorded. Serious adverse
      events, such as mortality, necrotizing enterocolitis (NEC), and sepsis, were
      monitored. A total of 29 babies received CPF fortified milk during the study
      period. The most common indication for starting CPF was previous intolerance to
      powder HMF. Feeding intolerance was noted in 4 infants on CPF. The growth
      velocity of infants was satisfactory (15.9 g/kg/day) after addition of CPF to
      feeds. The use of CPF as a fortifier in preterm babies considered at increased
      risk for feed intolerance seems well tolerated and facilitates adequate growth.
      Under close nutrition monitoring, this provides an additional option for human
      milk fortification in this challenging subgroup of preterm babies, especially in
      settings with limited human milk fortifier options.

PMID- 30287776
TI  - Lipopolysaccharide Challenge Reveals Hypothalamic-Pituitary-Adrenal Axis
      Dysfunction in Murine Systemic Lupus Erythematosus.
AB  - Crosstalk between the brain and innate immune system may be dysregulated in
      systemic lupus erythematosus (SLE), a chronic autoimmune disease that presents
      with dysautonomia and aberrant inflammation. The hypothalamic-pituitary-adrenal
      (HPA) axis is an endogenous neuro-endocrine-immune pathway that can regulate
      inflammation following activation of vagal afferents. We hypothesized that
      chronic inflammatory processes in SLE are in part due to HPA axis dysfunction, at
      the level of either the afferent vagal-paraventricular nuclei (PVN) interface,
      the anterior pituitary, and/or at the adrenal glands. To study this, we
      challenged female control and SLE mice with lipopolysaccharide (LPS) and measured
      c-Fos expression as an index of neuronal activation, plasma adrenocorticotrophic
      hormone (ACTH) as an index of anterior pituitary function, and plasma
      corticosterone as an index of adrenal function. We found that c-Fos expression in
      the PVN, and plasma ACTH and corticosterone were comparable between unchallenged
      SLE and control mice. PVN c-Fos was increased similarly in control and SLE mice
      three hours after LPS challenge; however, there were no changes in plasma ACTH
      amongst any experimental groups post inflammatory challenge. Plasma
      corticosterone was markedly increased in LPS-challenged SLE mice compared to
      their vehicle-treated counterparts, but not in controls. Paradoxically, following
      LPS challenge, brain and spleen TNF-alpha were elevated in LPS-challenged SLE
      mice despite heightened plasma corticosterone. This suggests that, despite normal
      c-Fos expression in the PVN and activation of the HPA axis following LPS
      challenge, this cumulative response may not adequately defend SLE mice against
      inflammatory stimuli, leading to abnormally heightened innate immune responses
      and peripheral inflammation.

PMID- 30287778
TI  - Assessment of a Rabies Virus Rapid Diagnostic Test for the Detection of
      Australian Bat Lyssavirus.
AB  - Australian bat lyssavirus (ABLV) is closely related to the classical rabies virus
      and has been associated with three human fatalities and two equine fatalities in
      Australia. ABLV infection in humans causes encephalomyelitis, resulting in fatal
      disease, but has no effective therapy. The virus is maintained in enzootic
      circulation within fruit bats (Pteropid spp.) and at least one insectivorous bat
      variety (Saccolaimus flaviventris). Most frequently, laboratory testing is
      conducted on pteropodid bat brains, either following a potential human exposure
      through bites, scratches and other direct contacts with bats, or as opportunistic
      assessment of sick or dead bats. The level of medical intervention and post
      exposure prophylaxis is largely determined on laboratory testing for
      antigen/virus as the demonstrable infection status of the in-contact bat. This
      study evaluates the comparative diagnostic performance of a lateral flow test,
      Anigen Rabies Ag detection rapid test (RDT), in pteropodid variant of ABLV
      infected bat brain tissues. The RDT demonstrated 100% agreement with the
      reference standard fluorescent antibody test on 43 clinical samples suggesting a
      potential application in rapid diagnosis of pteropodid variant of ABLV infection.
      A weighted Kappa value of 0.95 confirmed a high level of agreement between both
      tests.

PMID- 30287780
TI  - Identification of Safety-Related Opinion Leaders among Construction Workers:
      Evidence from Scaffolders of Metro Construction in Wuhan, China.
AB  - This study aimed to reveal opinion leaders who could impact their coworkers'
      safety-related performance in Chinese construction teams. Questionnaires were
      distributed to 586 scaffolders in Wuhan to understand their opinions about
      influencing their coworkers, serving as the foundation for a social network
      analysis to identify the potential opinion leaders among workers. A further
      controlled trial with the identified workers was conducted to select real opinion
      leaders by comparing their influence on others' safety-related behavior, followed
      by an association analysis to profile these opinion leaders. Two main sources of
      opinion leaders were identified: foremen and seasoned workers. Implementing
      interventions through opinion leaders resulted in better safety-related behavior
      performance. Furthermore, compared with education level, the association analysis
      results indicated that one's practical skills and familiarity with respondents
      was more important in the formulation of opinion leaders. This research
      introduces the concept of opinion leaders into construction safety and proposes
      an approach to identify and validate opinion leaders within a crew, thus
      providing a tool to improve behavior promotion on sites, as well as a new
      perspective for viewing interactions among workers.

PMID- 30287779
TI  - Effect of Collagen Hydrolysates from Silver Carp Skin (Hypophthalmichthys
      molitrix) on Osteoporosis in Chronologically Aged Mice: Increasing Bone
      Remodeling.
AB  - Osteoporosis is a common skeletal disorder in humans and gelatin hydrolysates
      from mammals have been reported to improve osteoporosis. In this study, 13-month
      old mice were used to evaluate the effects of collagen hydrolysates (CHs) from
      silver carp skin on osteoporosis. No significant differences were observed in
      mice body weight, spleen or thymus indices after daily intake of antioxidant
      collagen hydrolysates (ACH; 200 mg/kg body weight (bw) (LACH), 400 mg/kg bw
      (MACH), 800 mg/kg bw (HACH)), collagenase hydrolyzed collagen hydrolysates (CCH)
      or proline (400 mg/kg body weight) for eight weeks, respectively. ACH tended to
      improve bone mineral density, increase bone hydroxyproline content, enhance
      alkaline phosphatase (ALP) level and reduce tartrate-resistant acid phosphatase
      5b (TRAP-5b) activity in serum, with significant differences observed between the
      MACH and model groups (p < 0.05). ACH exerted a better effect on osteoporosis
      than CCH at the identical dose, whereas proline had no significant effect on
      repairing osteoporosis compared to the model group. Western blotting results
      demonstrated that CHs mainly increased bone remodeling by stimulating the
      transforming growth factor beta1 (TGF-beta1)/Smad signaling pathway and improving
      the interaction between collagen and alpha2beta1 integrin. The results indicated
      that CHs from fish could be applied to alleviate osteoporosis or treat bone loss.

PMID- 30287781
TI  - Sucrosomial(r) Iron: A New Generation Iron for Improving Oral Supplementation.
AB  - Iron deficiency (ID) is usually treated with oral iron salts, but up to 50% of
      patients complain of gastrointestinal side effects, leading to reduced treatment
      compliance. Intravenous (IV) iron formulations are increasingly safer, but there
      is still a risk of infusion and hypersensitivity reactions and the need for a
      venous access and infusion monitoring. Sucrosomial(r) iron (SI) is an innovative
      oral iron formulation in which ferric pyrophosphate is protected by a
      phospholipid bilayer plus a sucrester matrix (sucrosome), which is absorbed
      through para-cellular and trans-cellular routes (M cells). This confers SI unique
      structural, physicochemical and pharmacokinetic characteristics, together with
      high iron bioavailability and excellent gastrointestinal tolerance. The analysis
      of available evidence supports oral SI iron as a valid option for ID treatment,
      which is more efficacious and better tolerated than oral iron salts. SI has also
      demonstrated similar effectiveness, with lower risks, in patients usually
      receiving IV iron (e.g., chronic kidney disease, cancer, bariatric surgery).
      Thus, oral SI emerges as a most valuable first option for treating ID, even more
      for subjects with intolerance to or inefficacy of iron salts. Moreover, SI should
      be also considered as an alternative to IV iron for initial and/or maintenance
      treatment in different patient populations.

PMID- 30287777
TI  - Unusual Diversity of Sex Chromosomes in African Cichlid Fishes.
AB  - African cichlids display a remarkable assortment of jaw morphologies,
      pigmentation patterns, and mating behaviors. In addition to this previously
      documented diversity, recent studies have documented a rich diversity of sex
      chromosomes within these fishes. Here we review the known sex-determination
      network within vertebrates, and the extraordinary number of sex chromosomes
      systems segregating in African cichlids. We also propose a model for
      understanding the unusual number of sex chromosome systems within this clade.

PMID- 30287782
TI  - Cube-Rhombellane Related Structures: A Drug Perspective.
AB  - Rhombellanes represent a new class of structures, of which homeomorphs may be
      synthesized as real molecules. Cube-rhombellane is a double-shell structure, with
      vertices of degree 3 and 6, respectively. Several hypothetical
      structures/molecules were proposed and computed using molecular graph theory and
      coordination chemistry principles. Some geometries were optimized at the B3LYP/6
      31G (d, p) level of theory, followed by harmonic vibrational frequency analysis
      at the same level of theory, single point data were collected in view of
      molecular stability evaluation. Some of the bioactive functionalized structures
      were also proposed and explored by molecular mechanics (MM)-based conformational
      analysis, to check their internal mobility. Drug-like properties of the proposed
      molecular structures were compared with some existing nano-molecules (fullerenes,
      nanotubes). ADME and other physico-chemical characteristics were computed using
      commercial software. Substructures of the proposed molecules, useful in a future
      synthesis, were provided by retro combinatorial synthesis (RECAP). Computational
      results obtained are promising regarding ADME properties, drug-likeness and nano
      properties.

PMID- 30287784
TI  - Genotype Fingerprints Enable Fast and Private Comparison of Genetic Testing
      Results for Research and Direct-to-Consumer Applications.
AB  - Genetic testing has expanded out of the research laboratory into medical practice
      and the direct-to-consumer market. Rapid analysis of the resulting genotype data
      now has a significant impact. We present a method for summarizing personal
      genotypes as 'genotype fingerprints' that meets these needs. Genotype
      fingerprints can be derived from any single nucleotide polymorphism-based assay,
      and remain comparable as chip designs evolve to higher marker densities. We
      demonstrate that these fingerprints support distinguishing types of relationships
      among closely related individuals and closely related individuals from
      individuals from the same background population, as well as high-throughput
      identification of identical genotypes, individuals in known background
      populations, and de novo separation of subpopulations within a large cohort
      through extremely rapid comparisons. Although fingerprints do not preserve
      anonymity, they provide a useful degree of privacy by summarizing a genotype
      while preventing reconstruction of individual marker states. Genotype
      fingerprints are therefore well-suited as a format for public aggregation of
      genetic information to support ancestry and relatedness determination without
      revealing personal health risk status.

PMID- 30287783
TI  - Chemotherapeutic Efficacy of Implantable Antineoplastic-Treatment Protocols in an
      Optimal Mouse Model for Human Ovarian Carcinoma Cell Targeting.
AB  - The present study aimed to design and develop a nanocomposite drug delivery
      system employing an antineoplastic-loaded antibody functionalized nanomicelle
      encapsulated within a Chitosan-Poly(vinylpyrrolidone)-Poly(N-isopropylacrylamide)
      (C-P-N) hydrogel to form an in situ forming implant (ISFI), responsive to
      temperature and pH for cancer cell-targeting following intraperitoneal
      implantation. The optimum nanomicelle formulation was surface-functionalized with
      anti-MUC 16 (antibody) for the targeted delivery of methotrexate to human ovarian
      carcinoma (NIH:OVCAR-5) cells in Athymic nude mice that expressed MUC16, as a
      preferential form of intraperitoneal ovarian cancer (OC) chemotherapy. The cross
      linked interpenetrating C-P-N hydrogel was synthesized for the preparation of an
      in situ-forming implant (ISFI). Subsequently, the ISFI was fabricated by
      encapsulating a nanocomposite comprising of anti-MUC16 (antibody) functionalized
      methotrexate (MTX)-loaded poly(N-isopropylacrylamide)-b-poly(aspartic acid)
      (PNIPAAm-b-PASP) nanomicelles (AF(MTX)NM's) within the cross-linked C-P-N
      hydrogel. This strategy enabled specificity and increased the residence time of
      the nanomicelles at tumor sites over a period exceeding one month, enhancing
      uptake of drugs and preventing recurrence and chemo-resistance. Chemotherapeutic
      efficacy was tested on the optimal ovarian tumor-bearing Athymic nude mouse model
      and the results demonstrated tumor regression including reduction in mouse weight
      and tumor size, as well as a significant (p < 0.05) reduction in mucin 16 levels
      in plasma and ascitic fluid, and improved survival of mice after treatment with
      the experimental anti-MUC16/CA125 antibody-bound nanotherapeutic implant drug
      delivery system (ISFI) (p < 0.05). The study also concluded that ISFI could
      potentially be considered an important immuno-chemotherapeutic agent that could
      be employed in human clinical trials of advanced, and/or recurring, metastatic
      epithelial ovarian cancer (EOC). The development of this ISFI may circumvent the
      treatment flaws experienced with conventional systemic therapies, effectively
      manage recurrent disease and ultimately prolong disease-free intervals in ovarian
      cancer patients.

PMID- 30287785
TI  - Deep Learning Cluster Structures for Management Decisions: The Digital CEO.
AB  - This paper presents a Deep Learning (DL) Cluster Structure for Management
      Decisions that emulates the way the brain learns and makes choices by combining
      different learning algorithms. The proposed model is based on the Random Neural
      Network (RNN) Reinforcement Learning for fast local decisions and Deep Learning
      for long-term memory. The Deep Learning Cluster Structure has been applied in the
      Cognitive Packet Network (CPN) for routing decisions based on Quality of Service
      (QoS) metrics (Delay, Loss and Bandwidth) and Cyber Security keys (User, Packet
      and Node) which includes a layer of DL management clusters (QoS, Cyber and CEO)
      that take the final routing decision based on the inputs from the DL QoS clusters
      and RNN Reinforcement Learning algorithm. The model has been validated under
      different network sizes and scenarios. The simulation results are promising; the
      presented DL Cluster management structure as a mechanism to transmit, learn and
      make packet routing decisions is a step closer to emulate the way the brain
      transmits information, learns the environment and takes decisions.

PMID- 30287786
TI  - Using Low-Cost Sensors to Develop a High Precision Lifting Controller Device for
      an Overhead Crane-Insights and Hypotheses from Prototyping a Heavy Industrial
      Internet Project.
AB  - The subject of this study was the product development project creating a new
      innovative proof-of-concept (POC) prototype device that could control a connected
      industrial overhead crane in order to perform automatic or semi-automatic high
      precision lifts within a limited time frame. The development work focused on
      innovating a new measuring concept, which was parallel to finding suitable
      sensors for the application. Furthermore, the project resulted in a closed loop
      control system with Industrial Internet connected sensors and a user interface
      for factory workers. The prototyping journey is depicted to illustrate the
      decisions made during the product development project to contribute to both the
      pragmatic and the process discussion in the field of Industrial Internet. The
      purpose of this research was to explore and generate hypotheses for how new
      applications should be developed for heavy industry connected devices. The
      research question is: what are the implications of applying agile product
      development methods, such as Wayfaring, to heavy industrial machinery and
      Industrial Internet -based problems? The methodologies used in this paper, in
      addition to developing the device, are case study research and hypotheses
      generated from case studies. The hypotheses generated include that it is also
      possible to prototype large size connected machinery with low-cost and in a short
      time, and investment decisions for heavy Industrial Internet products become
      easier with concrete data from proof-of-concept prototypes by creating knowledge
      about the investment risk and the value proposition.

PMID- 30287787
TI  - Gait Type Analysis Using Dynamic Bayesian Networks.
AB  - This paper focuses on gait abnormality type identification-specifically,
      recognizing antalgic gait. Through experimentation, we demonstrate that detecting
      an individual's gait type is a viable biometric that can be used along with other
      common biometrics for applications such as forensics. To classify gait, the gait
      data is represented by coordinates that reflect the body joint coordinates
      obtained using a Microsoft Kinect v2 system. Features such as cadence, stride
      length, and other various joint angles are extracted from the input data. Using
      approaches such as the dynamic Bayesian network, the obtained features are used
      to model as well as perform gait type classification. The proposed approach is
      compared with other classification techniques and experimental results reveal
      that it is capable of obtaining a 88.68% recognition rate. The results illustrate
      the potential of using a dynamic Bayesian network for gait abnormality
      classification.

PMID- 30287788
TI  - Time-Dependent Degradation of Polyphenols from Thermally-Processed Berries and
      Their In Vitro Antiproliferative Effects against Melanoma.
AB  - Polyphenols are natural occurring micronutrients that can protect plants from
      natural weathering and are also helpful to humans. These compounds are abundantly
      found in fruits or berries. Because of berry seasonal availability and also due
      to their rapid degradation, people have found multiple ways to preserve them. The
      most common options are freezing or making jams. Polyphenol stability, during
      processing is a continuous challenge for the food industry. There are also
      multiple published data providing that they are sensitive to light, pH or high
      temperature, vectors which are all present during jam preparation. In this
      context the aim of this study was to assess phytochemical composition and
      bioactive compounds degradation after jam preparation. We also monitored their
      degradation during storage time and their in vitro antiproliferative potential
      when tested on melanoma cells. The obtained results revealed that when processed
      and stored in time, the bioactive compounds from berries jams are degrading, but
      they still exert antioxidant and antiproliferative potential. Prior to LC-MS
      analysis, polyphenolic compounds were identified as: flavonoids (anthocyanins
      (ANT), flavonols (FLA)) and non-flavonoid (hydroxycinnamic acids (HCA) and
      hydroxybenzoic acids (HBA)). The most significant decrease was observed for HCA
      compared to other classes of compounds. This variation is expected due to
      differences in constituents and phenolic types among different analyzed berries.

PMID- 30287789
TI  - Changes in Pain and Nutritional Intake Modulate Ultra-Running Performance: A Case
      Report.
AB  - Ultra-endurance running provides numerous physiological, psychological, and
      nutritional challenges to the athlete and supporting practitioners. We describe
      the changes in physiological status, psychological condition, and nutritional
      intake over the course of two 100-mile running races, with differing outcomes:
      non-completion and completion. Athlete perception of pain, freshness, and
      motivation differed between events, independent of rating of perceived exertion.
      Our data suggest that the integration of multiple sensations (freshness,
      motivation, hunger, pain, and thirst) produce performance. Increases in
      carbohydrate feeding (+5 g.h-1) and protein intake (+0.3 g.kg-1) also likely
      contributed to successful completion of a 100-mile race, by reducing the
      fractional utilization of maximal oxygen uptake and satiating hunger,
      respectively. Nutritional data support the notion that the gut is a trainable,
      and critical organ with respect to ultra-endurance performance. Finally, we
      propose future research to investigate the rate at which peak feeding occurs
      throughout ultra-endurance events, as this may further serve to personalize
      sports nutrition strategies.

PMID- 30287793
TI  - Resonator Based Switching Technique between Ultra Wide Band (UWB) and Single/Dual
      Continuously Tunable-Notch Behaviors in UWB Radar for Wireless Vital Signs
      Monitoring.
AB  - This paper presents a novel resonator that can switch and create three important
      behaviors within the same antenna using miniaturized capacitors. The resonator
      was integrated into conventional Ultra-Wide Band (UWB) antenna to achieve UWB and
      Single/Dual continuously tunable-notch behaviors. The Single/Dual notched was
      continuously tuned to our desired frequency band by changing the value of the
      capacitors. The antenna designed and fabricated to validate these behaviors had a
      compact size of 24 * 30.5 mm2, including the ground plane. The radiation patterns
      were very clean due to the placement of the proposed resonator in the special
      ground plane. Moreover, the presented novel resonator and switching technique was
      compared with the recently proposed resonators and their switching techniques.
      The prototype for the antenna was also developed in order to validate its
      performance in wireless vital signs monitoring. The presented miniaturized
      resonator based antenna was utilized for tumor sensing and simulations were
      provided in this regard. Moreover, the deployment of the proposed resonator based
      UWB antenna sensor in Pipeline Integrity Monitoring system was also investigated
      and discussed.

PMID- 30287791
TI  - Identification of a Novel PPAR-gamma Agonist through a Scaffold Tuning Approach.
AB  - Peroxisome proliferator-activated receptors (PPARs) are important targets in
      metabolic diseases including obesity, metabolic syndrome, diabetes, and non
      alcoholic fatty liver disease. Recently, they have been highlighted as attractive
      targets for the treatment of cardiovascular diseases and chronic myeloid
      leukemia. The PPAR agonist structure is consists of a polar head, a hydrophobic
      tail, and a linker. Each part interacts with PPARs through hydrogen bonds or
      hydrophobic interactions to stabilize target protein conformation, thus
      increasing its activity. Acidic head is essential for PPAR agonist activity. The
      aromatic linker plays an important role in making hydrophobic interactions with
      PPAR as well as adjusting the head-to-tail distance and conformation of the whole
      molecule. By tuning the scaffold of compound, the whole molecule could fit into
      the ligand-binding domain to achieve proper binding mode. We modified indol-3
      ylacetic acid scaffold to (indol-1-ylmethyl)benzoic acid, whereas 2,4
      dichloroanilide was fixed as the hydrophobic tail. We designed, synthesized, and
      assayed the in vitro activity of novel indole compounds with (indol-1
      ylmethyl)benzoic acid scaffold. Compound 12 was a more potent PPAR-gamma agonist
      than pioglitazone and our previous hit compound. Molecular docking studies may
      suggest the binding between compound 12 and PPAR-gamma, rationalizing its high
      activity.

PMID- 30287792
TI  - Conservation of k-mer Composition and Correlation Contribution between Introns
      and Intergenic Regions of Animalia Genomes.
AB  - In this study, we pairwise-compared multiple genome regions, including genes,
      exons, coding DNA sequences (CDS), introns, and intergenic regions of 39 Animalia
      genomes, including Deuterostomia (27 species) and Protostomia (12 species), by
      applying established k-mer-based (alignment-free) comparison methods. We found
      strong correlations between the sequence structure of introns and intergenic
      regions, individual organisms, and within wider phylogenetical ranges, indicating
      the conservation of certain structures over the full range of analyzed organisms.
      We analyzed these sequence structures by quantifying the contribution of
      different sets of DNA words to the average correlation value by decomposing the
      correlation coefficients with respect to these word sets. We found that the
      conserved structures within introns, intergenic regions, and between the two were
      mainly a result of conserved tandem repeats with repeat units <= 2 bp (e.g.,
      (AT)n), while other conserved sequence structures, such as those found between
      exons and CDS, were dominated by tandem repeats with repeat unit sizes of 3 bp in
      length and more complex DNA word patterns. We conclude that the conservation
      between intron and intergenic regions indicates a shared function of these
      sequence structures. Also, the similar differences in conserved structures with
      known origin, especially to the conservation between exons and CDS resulting from
      DNA codons, indicate that k-mer composition-based functional properties of
      introns and intergenic regions may differ from those of exons and CDS.

PMID- 30287790
TI  - Novel Functions of Death-Associated Protein Kinases through Mitogen-Activated
      Protein Kinase-Related Signals.
AB  - Death associated protein kinase (DAPK) is a calcium/calmodulin-regulated
      serine/threonine kinase; its main function is to regulate cell death. DAPK family
      proteins consist of DAPK1, DAPK2, DAPK3, DAPK-related apoptosis-inducing protein
      kinases (DRAK)-1 and DRAK-2. In this review, we discuss the roles and regulatory
      mechanisms of DAPK family members and their relevance to diseases. Furthermore, a
      special focus is given to several reports describing cross-talks between DAPKs
      and mitogen-activated protein kinases (MAPK) family members in various
      pathologies. We also discuss small molecule inhibitors of DAPKs and their
      potential as therapeutic targets against human diseases.

PMID- 30287794
TI  - First-principles Investigations of Magnetic Semiconductors: An example of
      Transition Metal Decorated Two-dimensional SnS Monolayer.
AB  - The absence of magnetic moments in pristine two-dimensional (2D) semiconducting
      materials has attracted many research interests. Transition-metal (TM) decoration
      has been found to be an effective strategy to introduce magnetic moments in non
      magnetic 2D semiconductors. However, the stability of TM atoms modified 2D
      semiconductors has not been well explored. Here, taking 2D Tin (II) sulfide (SnS)
      monolayer as a prototype, we explored the stability of magnetic semiconductors
      through this method. In our studies, all possible configurations of TM decoration
      have been considered, namely, adsorption on the intact surface, S vacancy, and Sn
      vacancy. Based on the energy gain and electronic analysis, our results revealed
      that most of the TM atoms will form a cluster, and only several TM atoms can be
      effectively doped into the SnS monolayer. Furthermore, the band calculations
      showed that only Mn substitution will give rise to a magnetic semiconductor.
      Thus, the reported results here provide some hidden information for further
      realization of the magnetic semiconductors and serve as a paradigm to prepare 2D
      magnetic semiconductors.

PMID- 30287795
TI  - Application of Ultrasound in Food Science and Technology: A Perspective.
AB  - Ultrasound is composed of mechanical sound waves that originate from molecular
      movements that oscillate in a propagation medium. The waves have a very high
      frequency, equal to approximately 20 kHz, are divided into two categories (i.e.,
      low-intensity and high-intensity waves) and cannot be perceived by the human ear.
      Nature has created the first ultrasound applications. Bats use ultrasound to
      navigate in the dark, and many cetaceans use echolocation to detect prey or
      obstacles using ultrasound produced by their vocal system. Ultrasound is commonly
      associated with the biomedical field. Today, ultrasound-based methods and
      equipment are available to detect organs, motion, tumour masses, and pre/post
      natal handicaps, and for kidney stone removal, physiotherapy, and aesthetic
      cures. However, ultrasound has found multiple applications in many other fields
      as well. In particular, ultrasound has recently been used in the food industry to
      develop various effective and reliable food processing applications. Therefore,
      this review summarizes the major applications of ultrasound in the food industry.
      The most common applications in the food industry include cell destruction and
      extraction of intracellular material. Depending on its intensity, ultrasound is
      used for the activation or deactivation of enzymes, mixing and homogenization,
      emulsification, dispersion, preservation, stabilization, dissolution and
      crystallization, hydrogenation, tenderization of meat, ripening, ageing and
      oxidation, and as an adjuvant for solid-liquid extraction for maceration to
      accelerate and to improve the extraction of active ingredients from different
      matrices, as well as the degassing and atomization of food preparations.

PMID- 30287796
TI  - Probing the Occurrence of Soluble Oligomers through Amyloid Aggregation Scaling
      Laws.
AB  - Drug discovery frequently relies on the kinetic analysis of physicochemical
      reactions that are at the origin of the disease state. Amyloid fibril formation
      has been extensively investigated in relation to prevalent and rare
      neurodegenerative diseases, but thus far no therapeutic solution has directly
      arisen from this knowledge. Other aggregation pathways producing smaller, hard-to
      detect soluble oligomers are increasingly appointed as the main reason for cell
      toxicity and cell-to-cell transmissibility. Here we show that amyloid
      fibrillation kinetics can be used to unveil the protein oligomerization state.
      This is illustrated for human insulin and ataxin-3, two model proteins for which
      the amyloidogenic and oligomeric pathways are well characterized. Aggregation
      curves measured by the standard thioflavin-T (ThT) fluorescence assay are shown
      to reflect the relative composition of protein monomers and soluble oligomers
      measured by nuclear magnetic resonance (NMR) for human insulin, and by dynamic
      light scattering (DLS) for ataxin-3. Unconventional scaling laws of kinetic
      measurables were explained using a single set of model parameters consisting of
      two rate constants, and in the case of ataxin-3, an additional order-of-reaction.
      The same fitted parameters were used in a discretized population balance that
      adequately describes time-course measurements of fibril size distributions. Our
      results provide the opportunity to study oligomeric targets using simple, high
      throughput compatible, biophysical assays.

PMID- 30287798
TI  - Oral Modified Release Multiple-Unit Particulate Systems: Compressed Pellets,
      Microparticles and Nanoparticles.
AB  - Oral modified-release multiparticulate dosage forms, which are also referred to
      as oral multiple-unit particulate systems, are becoming increasingly popular for
      oral drug delivery applications. The compaction of polymer-coated
      multiparticulates into tablets to produce a sustained-release dosage form is
      preferred over hard gelatin capsules. Moreover, multiparticulate tablets are a
      promising solution to chronic conditions, patients' adherence, and swallowing
      difficulties if incorporated into orodispersible matrices. Nonetheless, the
      compaction of multiparticulates often damages the functional polymer coat, which
      results in a rapid release of the drug substance and the subsequent loss of
      sustained-release properties. This review brings to the forefront key formulation
      variables that are likely to influence the compaction of coated multiparticulates
      into sustained-release tablets. It focusses on the tabletting of coated drug
      loaded pellets, microparticles, and nanoparticles with a designated section on
      each. Furthermore, it explores the various approaches that are used to evaluate
      the compaction behaviour of particulate systems.

PMID- 30287797
TI  - Machine Learning Approaches for Protein-Protein Interaction Hot Spot Prediction:
      Progress and Comparative Assessment.
AB  - Hot spots are the subset of interface residues that account for most of the
      binding free energy, and they play essential roles in the stability of protein
      binding. Effectively identifying which specific interface residues of protein
      protein complexes form the hot spots is critical for understanding the principles
      of protein interactions, and it has broad application prospects in protein design
      and drug development. Experimental methods like alanine scanning mutagenesis are
      labor-intensive and time-consuming. At present, the experimentally measured hot
      spots are very limited. Hence, the use of computational approaches to predicting
      hot spots is becoming increasingly important. Here, we describe the basic
      concepts and recent advances of machine learning applications in inferring the
      protein-protein interaction hot spots, and assess the performance of widely used
      features, machine learning algorithms, and existing state-of-the-art approaches.
      We also discuss the challenges and future directions in the prediction of hot
      spots.

PMID- 30287800
TI  - Bioinspired Honokiol Analogs and Their Evaluation for Activity on the
      Norepinephrine Transporter.
AB  - In traditional Asian medicinal systems, preparations of the root and stem bark of
      Magnolia species are widely used to treat anxiety and other nervous disturbances.
      The biphenyl-type neolignans honokiol and magnolol are the main constituents of
      Magnolia bark extracts. In the central nervous system, Magnolia bark preparations
      that contain honokiol are thought to primarily interact with gamma-aminobutyric
      acid A (GABAA) receptors. However, stress responses inherently involve the
      noradrenergic system, which has not been investigated in the pharmacological
      mechanism of honokiol. We present here interactions of honokiol and other
      synthesized biphenyl-type neolignans and diphenylmethane analogs with the
      norepinephrine transporter (NET), which is responsible for the synaptic clearance
      of norepinephrine and the target of many anxiolytics. Of the synthesized
      compounds, 16 are new chemical entities, which are fully characterized. The 52
      compounds tested show mild, non-potent interactions with NET (IC50 > 100 uM). It
      is thus likely that the observed anxiolytic effects of, e.g., Magnolia
      preparations, are not due to direct interaction with the noradrenergic system.

PMID- 30287799
TI  - The Role of Hydrogen Peroxide in Redox-Dependent Signaling: Homeostatic and
      Pathological Responses in Mammalian Cells.
AB  - Hydrogen peroxide (H2O2) is an important metabolite involved in most of the redox
      metabolism reactions and processes of the cells. H2O2 is recognized as one of the
      main molecules in the sensing, modulation and signaling of redox metabolism, and
      it is acting as a second messenger together with hydrogen sulfide (H2S) and
      nitric oxide (NO). These second messengers activate in turn a cascade of
      downstream proteins via specific oxidations leading to a metabolic response of
      the cell. This metabolic response can determine proliferation, survival or death
      of the cell depending on which downstream pathways (homeostatic, pathological, or
      protective) have been activated. The cells have several sources of H2O2 and
      cellular systems strictly control its concentration in different subcellular
      compartments. This review summarizes research on the role played by H2O2 in
      signaling pathways of eukaryotic cells and how this signaling leads to
      homeostatic or pathological responses.

PMID- 30287803
TI  - Primary Intrahepatic Squamous Cell Carcinoma with Histological Collision of
      Adenocarcinoma and Squamous Cell Carcinoma: A Case Report.
AB  - BACKGROUND Cholangiocarcinoma is a rare, aggressive biliary tract malignancy. On
      histopathology, most tumors are adenocarcinomas, while squamous cell carcinoma of
      the biliary tract is extremely rare. CASE REPORT An 82-year-old male was admitted
      due to the detection of a space-occupying lesion at S6 of the liver. On abdominal
      dynamic computed tomography, there was an irregular mass with inhomogeneous
      density associated with mild delayed enhancement in the tumor's peripheral zone,
      measuring approximately 22*25 mm, at S6, with secondary dilated biliary ducts of
      B6. Endoscopic retrograde cholangiopancreatography showed a severe stricture at
      B6. Brush cytology of B6 was positive for both adenocarcinoma and squamous cell
      carcinoma. Furthermore, mucous brushing cytology of the papilla of Vater was also
      positive for adenocarcinoma. Finally, the preoperative diagnosis of primary
      intrahepatic cholangiocarcinoma, combined with a cancer of the papilla of Vater,
      was made. The patient underwent both extended right lobectomy and
      pancreaticoduodenectomy. Histological examination showed that the majority (>99%)
      of this liver tumor was composed of keratinizing squamous cell carcinoma.
      CONCLUSIONS Squamous cell carcinoma of the biliary tree is very rare, since the
      majority of biliary tree tumors are adenocarcinomas. Cholangiocarcinoma
      containing a squamous cell component has a poor prognosis. To the best of our
      knowledge, this is the first case report of a primary intrahepatic squamous cell
      carcinoma that presented as a solid tumor showing clear histological collision
      between adenocarcinoma and squamous cell carcinoma and was successfully treated
      with hepatic resection and achieved disease-free survival of more than one year.

PMID- 30287801
TI  - Response of Cellular Innate Immunity to Cnidarian Pore-Forming Toxins.
AB  - A group of stable, water-soluble and membrane-bound proteins constitute the pore
      forming toxins (PFTs) in cnidarians. They interact with membranes to physically
      alter the membrane structure and permeability, resulting in the formation of
      pores. These lesions on the plasma membrane causes an imbalance of cellular ionic
      gradients, resulting in swelling of the cell and eventually its rupture. Of all
      cnidarian PFTs, actinoporins are by far the best studied subgroup with
      established knowledge of their molecular structure and their mode of pore-forming
      action. However, the current view of necrotic action by actinoporins may not be
      the only mechanism that induces cell death since there is increasing evidence
      showing that pore-forming toxins can induce either necrosis or apoptosis in a
      cell-type, receptor and dose-dependent manner. In this review, we focus on the
      response of the cellular immune system to the cnidarian pore-forming toxins and
      the signaling pathways that might be involved in these cellular responses. Since
      PFTs represent potential candidates for targeted toxin therapy for the treatment
      of numerous cancers, we also address the challenge to overcoming the
      immunogenicity of these toxins when used as therapeutics.

PMID- 30287804
TI  - Utilization of Standard Criteria Donor and Expanded Criteria Donor Kidneys After
      Kidney Allocation System Implementation.
AB  - BACKGROUND Implementation of the Kidney Allocation System (KAS) changed how
      kidneys are allocated and the information on which organ utilization decisions
      are based. We aimed to evaluate how KAS implementation changed kidney utilization
      and recipient outcomes. MATERIAL AND METHODS Using the United Network for Organ
      Sharing database, we identified recipients of kidney transplants from donors with
      kidney donor profile index (KDPI) of 61-90% in the 5-years pre- and 18-months
      post-KAS implementation and examined patient and graft survival and donor kidney
      discard rates based on standard criteria donor (SCD) or expanded criteria donor
      (ECD) status. RESULTS The proportion of ECD kidneys was unchanged pre- versus
      post-KAS. Post-KAS, SCD kidneys were less likely to be transplanted into young
      recipients while ECD kidneys were more likely to be transplanted. SCD kidneys in
      the post-KAS period conferred a 1.42 (95% CI: 1.18-1.73) times higher adjusted
      mortality and 2% lower 1-year survival (94.2% vs. 96.2%, P<0.001) but had
      unchanged graft failure compared to pre-KAS. For ECD kidneys, there was no
      difference in mortality or graft survival. The discard rate increased after KAS
      for both SCD and ECD kidneys (P<0.05) but was not different between SCD and ECD
      kidneys for any KDPI group. CONCLUSIONS After KAS implementation, patient
      survival for recipients of SCD kidneys was significantly worse.

PMID- 30287802
TI  - Pediatric Spinal Ependymomas.
AB  - BACKGROUND The aim of this study was to assess the clinical and radiological
      outcomes of surgical treatment for primary spinal ependymoma in children.
      MATERIAL AND METHODS Medical records of 46 primary spinal ependymoma patients who
      underwent surgery in BRSHH hospital during a 12-year period from 2004 to 2015
      were retrospectively reviewed. All pediatric patients (patient age <18 years)
      were selected as the core sample used for this study. RESULTS This series
      included 1 female and 2 male patients between the ages of 9 and 17 years with
      mean age 13.3+/-3.9 years. The mean preoperative course was 9.1+/-10.5 months.
      The most common location was the lumbar spinal cord (n=2). The most common
      presenting symptoms was lower-limb weakness and numbness. Two tumors were located
      intradural-intramedullary and 1 was located intradural-extramedullary. Gross
      total resection (GTR) was achieved in 2 patients, and a near-total resection was
      performed in 1 patient. No adjuvant treatment was received. The mean follow-up
      duration was 51.3+/-37.6 (17-98) months. No complications were recorded.
      Functional assessment of all patients by the latest follow-up evaluation showed
      good progress even though the patient is not fully recovered. At 6.3 years after
      the first operation, 1 patient presented with drop-seeding metastasis. No
      patients had neurofibromatosis type 2. CONCLUSIONS Laminoplasty and
      intraoperative neurophysiological monitorization are essential in surgical
      treatment of pediatric spinal ependymomas. GTR and recovery in pediatric spinal
      ependymoma are more likely than in adults. Despite the GTR, the risk of drop
      metastasis remains. Therefore, close clinical and radiological follow-up is
      recommended.

PMID- 30287805
TI  - [What works in selective prevention of alcohol and cannabis use among vulnerable
      young people?]
AB  - OBJECTIVE: Selective prevention tackle vulnerable factors associated to problem
      consumption and social exclusion. There are few effective programs in our
      context. Study aims were first to identify selective programs of alcohol and
      cannabis consumption for youths between 16-21, and second, to review
      intervention, evaluation and effects quality. METHODS: MEDLINE, PubMed, Google
      academics, EDDRA, SAMHSA, PBE and recommendations of PND were reviewed. Inclusion
      criteria were: 1) English/ Spanish programs, 2) publications <10 years, 3) target
      population 16- 21 years old 4) alcohol/ cannabis psicoeducational or
      socioeducational programs, 5) selective or selective/indicated programs and 6)
      evaluated programs. The description and quality of the intervention, its
      evaluation methods, and the presentation of its effects were assessed according
      to 20 criteria emerged from different recommendations. RESULTS: Fourteen programs
      followed the inclusion criteria, 10 of followed minimum quality intervention and
      evaluation criteria, however only 5 shown significant effects. Effective programs
      tackled negative emotions associated to consumption, promoted skills to cope it
      and reduce frequency of alcohol consumption, but rarely cannabis consumption.
      CONCLUSIONS: There are few selective prevention programs, and different studies
      shown that they have intervention or evaluation weaknesses, but mostly about
      program effects. The most effective are: PreVenture, The Climate Schools: Alcohol
      and Cannabis Course, Programa TND, Keepin' it REAL and Weekend is coming.

PMID- 30287806
TI  - Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a
      risk gene for comorbid nicotine dependence and major depression.
AB  - Smoking and major depression frequently co-occur, at least in part due to shared
      genetic risk. However, the nature of the shared genetic basis is poorly
      understood. To detect genetic risk variants for comorbid nicotine dependence (ND)
      and major depression (MD), we conducted genome-wide association study (GWAS) in
      two samples of African-American participants (Yale-Penn 1 and 2) using linear
      mixed model, followed by meta-analysis. 3724 nicotine-exposed subjects were
      analyzed: 2596 from Yale-Penn-1 and 1128 from Yale-Penn-2. Continuous measures
      (Fagerstrom Test for Nicotine Dependence (FTND) scores and DSM-IV MD criteria)
      rather than disorder status were used to maximize the power of the GWAS.
      Genotypes were ascertained using the Illumina HumanOmni1-Quad array (Yale-Penn-1
      sample) or the Illumina HumanCore Exome array (Yale-Penn-2 sample), followed by
      imputation based on the 1000 Genomes reference panel. An intronic variant at the
      GRIA4 locus, rs68081839, was significantly associated with ND-MD comorbidity
      (beta = 0.69 [95% CI, 0.43-0.89], P = 1.53 * 10-8). GRIA4 encodes an AMPA
      sensitive glutamate receptor that mediates fast excitatory synaptic transmission
      and neuroplasticity. Conditional analyses revealed that the association was
      explained jointly by both traits. Enrichment analysis showed that the top risk
      genes and genes co-expressed with GRIA4 are enriched in cell adhesion, calcium
      ion binding, and synapses. They also have enriched expression in the brain and
      they have been implicated in the risk for other neuropsychiatric disorders.
      Further research is needed to determine the replicability of these findings and
      to identify the biological mechanisms through which genetic risk for each
      condition is conveyed.

PMID- 30287807
TI  - The Use of International Classification of Diseases Codes to Identify Patients
      with Pancreatitis: A Systematic Review and Meta-analysis of Diagnostic Accuracy
      Studies.
AB  - BACKGROUND: Hospital discharge codes are increasingly used in gastroenterology
      research, but their accuracy in the setting of acute pancreatitis (AP) and
      chronic pancreatitis (CP), one of the most frequent digestive diseases, has never
      been assessed systematically. The aim was to conduct a systematic literature
      review and determine accuracy of diagnostic codes for AP and CP, as well as the
      effect of covariates. METHODS: Three databases (Pubmed, EMBASE and Scopus) were
      searched by two independent reviewers for relevant studies that used
      International Classification of Disease (ICD) codes. Summary estimates of
      sensitivity, specificity and positive predictive value were obtained from
      bivariate random-effects regression models. Sensitivity and subgroup analyses
      according to recurrence of AP and age of the study population were performed.
      RESULTS: A total of 24 cohorts encompassing 18,106 patients were included. The
      pooled estimates of sensitivity and specificity of ICD codes for AP were 0.85 and
      0.96, respectively. The pooled estimates of sensitivity and specificity of ICD
      codes for CP were 0.75 and 0.94, respectively. The positive predictive value of
      ICD codes was 0.71 for either AP or CP. It increased to 0.78 when applied to
      incident episode of AP only. The positive predictive value decreased to 0.68 when
      the ICD codes were applied to paediatric patients. CONCLUSION: Nearly three out
      of ten patients are misidentified as having either AP or CP with the
      indiscriminate use of ICD codes. Limiting the use of ICD codes to adult patients
      with incident episode of AP may improve identification of patients with
      pancreatitis in administrative databases.

PMID- 30287809
TI  - Twist angle-dependent conductivities across MoS2/graphene heterojunctions.
AB  - Van der Waals heterostructures stacked from different two-dimensional materials
      offer a unique platform for addressing many fundamental physics and construction
      of advanced devices. Twist angle between the two individual layers plays a
      crucial role in tuning the heterostructure properties. Here we report the
      experimental investigation of the twist angle-dependent conductivities in
      MoS2/graphene van der Waals heterojunctions. We found that the vertical
      conductivity of the heterojunction can be tuned by ~5 times under different twist
      configurations, and the highest/lowest conductivity occurs at a twist angle of 0
      degrees /30 degrees . Density functional theory simulations suggest that this
      conductivity change originates from the transmission coefficient difference in
      the heterojunctions with different twist angles. Our work provides a guidance in
      using the MoS2/graphene heterojunction for electronics, especially on reducing
      the contact resistance in MoS2 devices as well as other TMDCs devices contacted
      by graphene.

PMID- 30287808
TI  - Androgen deprivation promotes neuroendocrine differentiation and angiogenesis
      through CREB-EZH2-TSP1 pathway in prostate cancers.
AB  - The incidence of aggressive neuroendocrine prostate cancers (NEPC) related to
      androgen-deprivation therapy (ADT) is rising. NEPC is still poorly understood,
      such as its neuroendocrine differentiation (NED) and angiogenic phenotypes. Here
      we reveal that NED and angiogenesis are molecularly connected through EZH2
      (enhancer of zeste homolog 2). NED and angiogenesis are both regulated by ADT
      activated CREB (cAMP response element-binding protein) that in turn enhances EZH2
      activity. We also uncover anti-angiogenic factor TSP1 (thrombospondin-1, THBS1)
      as a direct target of EZH2 epigenetic repression. TSP1 is downregulated in
      advanced prostate cancer patient samples and negatively correlates with NE
      markers and EZH2. Furthermore, castration activates the CREB/EZH2 axis,
      concordantly affecting TSP1, angiogenesis and NE phenotypes in tumor xenografts.
      Notably, repressing CREB inhibits the CREB/EZH2 axis, tumor growth, NED, and
      angiogenesis in vivo. Taken together, we elucidate a new critical pathway,
      consisting of CREB/EZH2/TSP1, underlying ADT-enhanced NED and angiogenesis during
      prostate cancer progression.

PMID- 30287810
TI  - CLOCK and BMAL1 stabilize and activate RHOA to promote F-actin formation in
      cancer cells.
AB  - Circadian genes control most of the physiological functions in cancer cells,
      including cell proliferation, migration, and invasion. The CLOCK and BMAL1
      complex plays a central role in circadian rhythms. Previous studies have shown
      that circadian genes may act as oncogenes or tumor-suppressor genes. In addition,
      F-actin, regulated by RHOA, has been shown to participate in tumor progression.
      However, the roles of the CLOCK and BMAL1 genes in the regulation of tumor
      progression via the RHOA-ROCK-CFL pathway remain largely unclear. Here we first
      indicate that the rearrangement of F-actin is regulated by CLOCK and BMAL1. We
      found that CLOCK and BMAL1 can upregulate RHOA expression by inhibiting CUL3
      mediated ubiquitination and activate RHOA by reducing the interaction between
      RHOA and RhoGDI. Consequently, CLOCK and BMAL1 control the expression of the
      components of the RHOA-ROCK-CFL pathway, which alters the dynamics of F-actin/G
      actin turnover and promotes cancer cell proliferation, migration, and invasion.
      In conclusion, our research proposes a novel insight into the role of CLOCK and
      BMAL1 in tumor cells.

PMID- 30287811
TI  - Sex-specific correlation of IGFBP-2 and IGFBP-3 with vitamin D status in adults
      with obesity: a cross-sectional serum proteomics study.
AB  - OBJECTIVE: Subjects with low vitamin D levels are at risk of cardiometabolic
      disease. The aim of this study was to identify novel serological markers linking
      vitamin D status with cardiometabolic profile in non-diabetic adults with
      obesity. METHODS: For the discovery phase, we used quantitative serum proteomics
      in sex-matched, age-matched and BMI-matched subjects with obesity [BMI: 25-35
      kg/m2] and low [25(OH)D < 50 nmol/L] vs. high vitamin D status [25(OH)D > 50
      nmol/L] (n = 16). For the validation phase, we performed ELISA in a larger cohort
      with similar characteristics (n = 179). RESULTS: We identified 423 and 549
      differentially expressed proteins in the high vs. low vitamin D groups of the
      male and female cohorts, respectively. The small molecule biochemistry protein
      networks and the glycolysis|gluconeogenesis pathway were significantly enriched
      in the DEPs of both sexes. As surrogate markers to these processes, the insulin
      like growth factor binding protein -2  (IGFBP-2) was upregulated in males,
      whereas   IGFBP-3 was upregulated in females from the high Vitamin D status. This
      sex-specific trend  was confirmed using Luminex ELISA to an independent but
      clinically analogous cohort of males (n = 84, p = 0.002) and females (n = 95, p =
      0.03). CONCLUSIONS: The high Vitamin D status correlated with the serological
      upregulation of IGFBP-2 in males and IGFBP-3 in females with obesity and may
      constitute surrogate markers of risk reduction of cardiometabolic disease.

PMID- 30287813
TI  - Sustainable scalable synthesis of sulfide nanocrystals at low cost with an ionic
      liquid sulfur precursor.
AB  - Increasing the sustainability of nanocrystals is crucial to their application and
      the protection of the environment. Sulfur precursors for their synthesis are
      commonly obtained through multiple steps from H2S, only to be converted back to
      H2S during the synthesis of the nanocrystals. This convoluted process requires
      energy, reduces yields, increases waste and auxiliaries, and complicates
      recycling. Using H2S directly could drastically improve sustainability, but is
      prevented by toxicity and handling. We here show that H2S is stabilized by
      reaction with oleylamine (the most common and versatile ligand in nanoparticle
      synthesis) to form an ionic liquid precursor that addresses all major principles
      of green chemistry: it is made in one exothermic step, it leaves the reaction
      yielding a safer product and allowing the separate recycling of the precursors,
      and it produces high quality nanocrystals with high yields (sulfur yield > 70%)
      and concentrations (90 g L-1) in ambient conditions.

PMID- 30287812
TI  - DNA damage sensitivity of SWI/SNF-deficient cells depends on TFIIH subunit
      p62/GTF2H1.
AB  - Mutations in SWI/SNF genes are amongst the most common across all human cancers,
      but efficient therapeutic approaches that exploit vulnerabilities caused by
      SWI/SNF mutations are currently lacking. Here, we show that the SWI/SNF ATPases
      BRM/SMARCA2 and BRG1/SMARCA4 promote the expression of p62/GTF2H1, a core subunit
      of the transcription factor IIH (TFIIH) complex. Inactivation of either ATPase
      subunit downregulates GTF2H1 and therefore compromises TFIIH stability and
      function in transcription and nucleotide excision repair (NER). We also
      demonstrate that cells with permanent BRM or BRG1 depletion have the ability to
      restore GTF2H1 expression. As a consequence, the sensitivity of SWI/SNF-deficient
      cells to DNA damage induced by UV irradiation and cisplatin treatment depends on
      GTF2H1 levels. Together, our results expose GTF2H1 as a potential novel
      predictive marker of platinum drug sensitivity in SWI/SNF-deficient cancer cells.

PMID- 30287814
TI  - Recommendations for acquisition, interpretation and reporting of whole body low
      dose CT in patients with multiple myeloma and other plasma cell disorders: a
      report of the IMWG Bone Working Group.
AB  - Whole Body Low Dose CT (WBLDCT) has important advantages as a first-line imaging
      modality for bone disease assessment in patients with plasma cell disorders and
      has been included in the 2014 International Myeloma Working Group (IMWG) criteria
      for multiple myeloma (MM) definition. Nevertheless, standardization guidelines
      for the optimal use of WBLDCT in MM patients are still lacking, preventing its
      more widespread use, both in daily practice and clinical trials. The aim of this
      report by the Bone Group of the IMWG is to provide practical recommendations for
      the acquisition, interpretation and reporting of WBLDCT in patients with multiple
      myeloma and other plasma cell disorders.

PMID- 30287815
TI  - Selective prebiotic conversion of pyrimidine and purine anhydronucleosides into
      Watson-Crick base-pairing arabino-furanosyl nucleosides in water.
AB  - Prebiotic nucleotide synthesis is crucial to understanding the origins of life on
      Earth. There are numerous candidates for life's first nucleic acid, however,
      currently no prebiotic method to selectively and concurrently synthesise the
      canonical Watson-Crick base-pairing pyrimidine (C, U) and purine (A, G)
      nucleosides exists for any genetic polymer. Here, we demonstrate the divergent
      prebiotic synthesis of arabinonucleic acid (ANA) nucleosides. The complete set of
      canonical nucleosides is delivered from one reaction sequence, with regiospecific
      glycosidation and complete furanosyl selectivity. We observe photochemical 8
      mercaptopurine reduction is efficient for the canonical purines (A, G), but not
      the non-canonical purine inosine (I). Our results demonstrate that synthesis of
      ANA may have been facile under conditions that comply with plausible geochemical
      environments on early Earth and, given that ANA is capable of encoding RNA/DNA
      compatible information and evolving to yield catalytic ANA-zymes, ANA may have
      played a critical role during the origins of life.

PMID- 30287816
TI  - A ballistic graphene superconducting microwave circuit.
AB  - Josephson junctions (JJ) are a fundamental component of microwave quantum
      circuits, such as tunable cavities, qubits, and parametric amplifiers. Recently
      developed encapsulated graphene JJs, with supercurrents extending over micron
      distance scales, have exciting potential applications as a new building block for
      quantum circuits. Despite this, the microwave performance of this technology has
      not been explored. Here, we demonstrate a microwave circuit based on a ballistic
      graphene JJ embedded in a superconducting cavity. We directly observe a gate
      tunable Josephson inductance through the resonance frequency of the device and,
      using a detailed RF model, we extract this inductance quantitatively. We also
      observe the microwave losses of the device, and translate this into sub-gap
      resistances of the junction at MUeV energy scales, not accessible in DC
      measurements. The microwave performance we observe here suggests that graphene
      Josephson junctions are a feasible platform for implementing coherent quantum
      circuits.

PMID- 30287818
TI  - Infected Pancreatic Necrosis due to Multidrug-Resistant Organisms and Persistent
      Organ failure Predict Mortality in Acute Pancreatitis.
AB  - BACKGROUND: Organ failure determines outcome in acute pancreatitis (AP). It is
      controversial if infected pancreatic necrosis (IPN) is also an independent
      determinant of mortality. We hypothesized that the predictors of mortality in AP
      might have changed with advances in management and consequent decline in
      mortality over the past decades. Our objective was to study the predictors of
      mortality in patients with AP. METHODS: Consecutive patients with a first episode
      of AP hospitalized from January 2015 to December 2016 were included in an
      observational study. Patients with IPN were treated with a conservative first
      approach followed by intervention. Necrosectomy, if required, was delayed beyond
      4 weeks and done primarily employing minimally invasive techniques. The primary
      outcome measure was independent predictors of in-hospital mortality. RESULTS: Of
      209 patients with AP, 81 (39%) had persistent organ failure (OF) and 108 (52%)
      developed IPN. Overall, 46/209 (22%) patients died. Independent predictors of
      mortality were OF (odds ratio [OR]19; 95% CI: 6.1-58.8), and IPN due to infection
      with multidrug resistant (MDR) organisms (OR: 8.4; 95% CI:3.1-22.5). Infected
      pancreatic necrosis by itself was not found to be a significant predictor of
      mortality (OR 2; 95% CI: 0.4-9.5). CONCLUSION: Persistent OF and complicated IPN
      due to MDR infection were independent predictors of mortality in patients with
      AP. Renewed efforts to prevent MDR infection with antibiotic stewardship and
      strategies for early control of sepsis are urgently required.

PMID- 30287817
TI  - Atomic cobalt as an efficient electrocatalyst in sulfur cathodes for superior
      room-temperature sodium-sulfur batteries.
AB  - The low-cost room-temperature sodium-sulfur battery system is arousing extensive
      interest owing to its promise for large-scale applications. Although significant
      efforts have been made, resolving low sulfur reaction activity and severe
      polysulfide dissolution remains challenging. Here, a sulfur host comprised of
      atomic cobalt-decorated hollow carbon nanospheres is synthesized to enhance
      sulfur reactivity and to electrocatalytically reduce polysulfide into the final
      product, sodium sulfide. The constructed sulfur cathode delivers an initial
      reversible capacity of 1081 mA h g-1 with 64.7% sulfur utilization rate;
      significantly, the cell retained a high reversible capacity of 508 mA h g-1 at
      100 mA g-1 after 600 cycles. An excellent rate capability is achieved with an
      average capacity of 220.3 mA h g-1 at the high current density of 5 A g-1.
      Moreover, the electrocatalytic effects of atomic cobalt are clearly evidenced by
      operando Raman spectroscopy, synchrotron X-ray diffraction, and density
      functional theory.

PMID- 30287819
TI  - Improvement and extension of anti-EGFR targeting in breast cancer therapy by
      integration with the Avidin-Nucleic-Acid-Nano-Assemblies.
AB  - Nowadays, personalized cancer therapy relies on small molecules, monoclonal
      antibodies, or antibody-drug conjugates (ADC). Many nanoparticle (NP)-based drug
      delivery systems are also actively investigated, but their advantage over ADCs
      has not been demonstrated yet. Here, using the Avidin-Nucleic-Acid-Nano
      Assemblies (ANANAS), a class of polyavidins multifuctionalizable with
      stoichiometric control, we compare quantitatively anti-EGFR antibody(cetuximab)
      targeted NPs to the corresponding ADC. We show that ANANAS tethering of cetuximab
      promotes a more efficient EGFR-dependent vesicle-mediated internalization.
      Cetuximab-guided ANANAS carrying doxorubicin are more cytotoxic in vitro and much
      more potent in vivo than the corresponding ADC, leading to 43% tumor reduction at
      low drug dosage (0.56 mg/kg). Advantage of cetuximab-guided ANANAS with respect
      to the ADC goes beyond the increase in drug-to-antibody ratio. Even if further
      studies are needed, we propose that NP tethering could expand application of the
      anti-EGFR antibody to a wider number of cancer patients including the KRAS
      mutated ones, currently suffering from poor prognosis.

PMID- 30287820
TI  - Observation of Coulomb gap in the quantum spin Hall candidate single-layer 1T'
      WTe2.
AB  - The two-dimensional topological insulators host a full gap in the bulk band,
      induced by spin-orbit coupling (SOC) effect, together with the topologically
      protected gapless edge states. However, it is usually challenging to suppress the
      bulk conductance and thus to realize the quantum spin Hall (QSH) effect. In this
      study, we find a mechanism to effectively suppress the bulk conductance. By using
      the quasiparticle interference technique with scanning tunneling spectroscopy, we
      demonstrate that the QSH candidate single-layer 1T'-WTe2 has a semimetal bulk
      band structure with no full SOC-induced gap. Surprisingly, in this two
      dimensional system, we find the electron-electron interactions open a Coulomb gap
      which is always pinned at the Fermi energy (EF). The opening of the Coulomb gap
      can efficiently diminish the bulk state at the EF and supports the observation of
      the quantized conduction of topological edge states.

PMID- 30287821
TI  - Resolving the mechanisms of hygroscopic growth and cloud condensation nuclei
      activity for organic particulate matter.
AB  - Hygroscopic growth and cloud condensation nuclei activation are key processes for
      accurately modeling the climate impacts of organic particulate matter.
      Nevertheless, the microphysical mechanisms of these processes remain unresolved.
      Here we report complex thermodynamic behaviors, including humidity-dependent
      hygroscopicity, diameter-dependent cloud condensation nuclei activity, and liquid
      liquid phase separation in the laboratory for biogenically derived secondary
      organic material representative of similar atmospheric organic particulate
      matter. These behaviors can be explained by the non-ideal mixing of water with
      hydrophobic and hydrophilic organic components. The non-ideality-driven liquid
      liquid phase separation further enhances water uptake and induces lowered surface
      tension at high relative humidity, which result in a lower barrier to cloud
      condensation nuclei activation. By comparison, secondary organic material
      representing anthropogenic sources does not exhibit complex thermodynamic
      behavior. The combined results highlight the importance of detailed thermodynamic
      representations of the hygroscopicity and cloud condensation nuclei activity in
      models of the Earth's climate system.

PMID- 30287823
TI  - Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients
      and 11,241 controls.
AB  - Pathogenic variants in highly penetrant genes are useful for the diagnosis,
      therapy, and surveillance for hereditary breast cancer. Large-scale studies are
      needed to inform future testing and variant classification processes in Japanese.
      We performed a case-control association study for variants in coding regions of
      11 hereditary breast cancer genes in 7051 unselected breast cancer patients and
      11,241 female controls of Japanese ancestry. Here, we identify 244 germline
      pathogenic variants. Pathogenic variants are found in 5.7% of patients, ranging
      from 15% in women diagnosed <40 years to 3.2% in patients >=80 years, with
      BRCA1/2, explaining two-thirds of pathogenic variants identified at all ages.
      BRCA1/2, PALB2, and TP53 are significant causative genes. Patients with
      pathogenic variants in BRCA1/2 or PTEN have significantly younger age at
      diagnosis. In conclusion, BRCA1/2, PALB2, and TP53 are the major hereditary
      breast cancer genes, irrespective of age at diagnosis, in Japanese women.

PMID- 30287824
TI  - Extracts of Polypore Mushroom Mycelia Reduce Viruses in Honey Bees.
AB  - Waves of highly infectious viruses sweeping through global honey bee populations
      have contributed to recent declines in honey bee health. Bees have been observed
      foraging on mushroom mycelium, suggesting that they may be deriving medicinal or
      nutritional value from fungi. Fungi are known to produce a wide array of
      chemicals with antimicrobial activity, including compounds active against
      bacteria, other fungi, or viruses. We tested extracts from the mycelium of
      multiple polypore fungal species known to have antiviral properties. Extracts
      from amadou (Fomes) and reishi (Ganoderma) fungi reduced the levels of honey bee
      deformed wing virus (DWV) and Lake Sinai virus (LSV) in a dose-dependent manner.
      In field trials, colonies fed Ganoderma resinaceum extract exhibited a 79-fold
      reduction in DWV and a 45,000-fold reduction in LSV compared to control colonies.
      These findings indicate honey bees may gain health benefits from fungi and their
      antimicrobial compounds.

PMID- 30287822
TI  - High-throughput in vivo mapping of RNA accessible interfaces to identify
      functional sRNA binding sites.
AB  - Herein we introduce a high-throughput method, INTERFACE, to reveal the capacity
      of contiguous RNA nucleotides to establish in vivo intermolecular RNA
      interactions for the purpose of functional characterization of intracellular RNA.
      INTERFACE enables simultaneous accessibility interrogation of an unlimited number
      of regions by coupling regional hybridization detection to transcription
      elongation outputs measurable by RNA-seq. We profile over 900 RNA interfaces in
      71 validated, but largely mechanistically under-characterized, Escherichia coli
      sRNAs in the presence and absence of a global regulator, Hfq, and find that two
      thirds of tested sRNAs feature Hfq-dependent regions. Further, we identify in
      vivo hybridization patterns that hallmark functional regions to uncover mRNA
      targets. In this way, we biochemically validate 25 mRNA targets, many of which
      are not captured by typically tested, top-ranked computational predictions. We
      additionally discover direct mRNA binding activity within the GlmY terminator,
      highlighting the information value of high-throughput RNA accessibility data.

PMID- 30287825
TI  - Stepwise oxygenation of the Paleozoic atmosphere.
AB  - Oxygen is essential for animal life, and while geochemical proxies have been
      instrumental in determining the broad evolutionary history of oxygen on Earth,
      much of our insight into Phanerozoic oxygen comes from biogeochemical modelling.
      The GEOCARBSULF model utilizes carbon and sulphur isotope records to produce the
      most detailed history of Phanerozoic atmospheric O2 currently available. However,
      its predictions for the Paleozoic disagree with geochemical proxies, and with non
      isotope modelling. Here we show that GEOCARBSULF oversimplifies the geochemistry
      of sulphur isotope fractionation, returning unrealistic values for the O2 sourced
      from pyrite burial when oxygen is low. We rebuild the model from first
      principles, utilizing an improved numerical scheme, the latest carbon isotope
      data, and we replace the sulphur cycle equations in line with forwards modelling
      approaches. Our new model, GEOCARBSULFOR, produces a revised, highly-detailed
      prediction for Phanerozoic O2 that is consistent with available proxy data, and
      independently supports a Paleozoic Oxygenation Event, which likely contributed to
      the observed radiation of complex, diverse fauna at this time.

PMID- 30287826
TI  - Multi-Band Sensing for Dielectric Property of Chemicals Using Metamaterial
      Integrated Microfluidic Sensor.
AB  - The growth of the chemical industry has brought tremendous challenges to chemical
      sensing technology. Chemical sensors based on metamaterials have great potential
      because of their label-free and non-destructive characteristics. However,
      metamaterials applied in chemical sensing have mainly been investigated from the
      measurement of sample concentration or the determination of the dielectric
      properties at a fixed frequency. Here we present a metamaterial integrated
      microfluidic (MIM) sensor for the multi-band sensing for dielectric property of
      chemicals, which is promising for the identification of chemicals. The MIM sensor
      mainly consists of multiple pair of high sensitive symmetrical double split-ring
      resonators (DSRRs) and meandering microfluidic channels with a capacity of only 4
      MUL. A dielectric model has been innovatively established and experimentally
      verified to accurately estimate the complex permittivity and thus realize the
      multi-band sensing of dielectric property of chemicals. With the increase in the
      number of resonators in the sensor, a dielectric spectrum like curve could be
      obtained for more detailed dielectric information. This work delivers a
      miniaturized, reusable, label-free and non-destructive metamaterial-microfluidic
      solution and paves a way of the multi-band sensing for dielectric property of
      chemicals.

PMID- 30287827
TI  - Effect of central lesions on a spinal circuit facilitating human wrist flexors.
AB  - A putative spinal circuit with convergent inputs facilitating human wrist flexors
      has been recently described. This study investigated how central nervous system
      lesions may affect this pathway. We measured the flexor carpi radialis H-reflex
      conditioned with stimulation above motor threshold to the extensor carpi radialis
      at different intervals in fifteen patients with stroke and nine with spinal cord
      injury. Measurements after stroke revealed a prolonged facilitation of the H
      reflex, which replaced the later suppression seen in healthy subjects at longer
      intervals (30-60 ms). Measurements in patients with incomplete spinal cord injury
      at cervical level revealed heterogeneous responses. Results from patients with
      stroke could represent either an excessive facilitation or a loss of inhibition,
      which may reflect the development of spasticity. Spinal cord injury results
      possibly reflect damage to the segmental interneuron pathways. We report a
      straightforward method to assess changes to spinal circuits controlling wrist
      flexors after central nervous system lesion.

PMID- 30287829
TI  - Author Correction: Impact of pore anisotropy on the thermal conductivity of
      porous Si nanowires.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30287828
TI  - Altered cerebral benzodiazepine receptor binding in post-traumatic stress
      disorder.
AB  - Agonists of the gamma-aminobutyric acid (GABA) type A benzodiazepine (BZD)
      receptor exert anxiolytic effects in anxiety disorders, raising the possibility
      that altered GABA-ergic function may play a role in the pathophysiology of
      anxiety disorders, such as post-traumatic stress disorder (PTSD). However, few
      neuroimaging studies have assessed the function or binding potential of the
      central GABAA BZD receptor system in PTSD. Therefore, our aim was to compare the
      BZD receptor binding potential between PTSD patients and healthy controls. Twelve
      medication-free participants with a current diagnosis of PTSD and 15 matched
      healthy controls underwent positron emission tomography (PET) imaging using [11C]
      flumazenil. Structural magnetic resonance imaging (MRI) scans were obtained and
      co-registered to the PET images to permit co-location of neuroanatomical
      structures in the lower resolution PET image data. Compared to healthy controls,
      PTSD patients exhibited increased BZD binding in the caudal anterior cingulate
      cortex and precuneus (p's < 0.05). Severity of PTSD symptoms positively
      correlated with BZD binding in the left mid- and anterior insular cortices. This
      study extends previous findings by suggesting that central BZD receptor system
      involvement in PTSD includes portions of the default mode and salience networks,
      along with insular regions that support interoception and autonomic arousal.

PMID- 30287830
TI  - Two-photon polymerisation 3D printed freeform micro-optics for optical coherence
      tomography fibre probes.
AB  - Miniaturised optical coherence tomography (OCT) fibre-optic probes have enabled
      high-resolution cross-sectional imaging deep within the body. However, existing
      OCT fibre-optic probe fabrication methods cannot generate miniaturised freeform
      optics, which limits our ability to fabricate probes with both complex optical
      function and dimensions comparable to the optical fibre diameter. Recently, major
      advances in two-photon direct laser writing have enabled 3D printing of arbitrary
      three-dimensional micro/nanostructures with a surface roughness acceptable for
      optical applications. Here, we demonstrate the feasibility of 3D printing of OCT
      probes. We evaluate the capability of this method based on a series of
      characterisation experiments. We report fabrication of a micro-optic containing
      an off-axis paraboloidal total internal reflecting surface, its integration as
      part of a common-path OCT probe, and demonstrate proof-of-principle imaging of
      biological samples.

PMID- 30287831
TI  - Analysis of the mechanisms regulating the expression of isoprenoid biosynthesis
      genes in hydroponically-grown Nicotiana benthamiana plants using virus-induced
      gene silencing.
AB  - Secondary metabolites in plants play important roles in defence against biotic
      and abiotic stresses. Although the biosynthesis pathways of secondary metabolites
      have been extensively studied, the regulatory mechanism of gene expression
      involved in these pathways remains poorly understood. In this study, we develop a
      virus-induced gene silencing (VIGS) system that enables a rapid analysis of the
      regulatory mechanism of genes involved in the biosynthesis of isoprenoids, one of
      the largest groups in secondary metabolites, using hydroponically-grown Nicotiana
      benthamiana. Using VIGS, we successfully reduced the transcript levels of 3
      hydroxy-3-methylglutaryl-CoA reductase 1 (HMGR1), cycloartenol synthase 1 (CAS1),
      sterol side chain reductase 2 (SSR2) and S-adenosyl-L-Met-dependent C-24 sterol
      methyltransferase 1 (SMT1) in leaf, stem and root tissues in approximately 2
      weeks. We identified novel feedback and feed-forward regulation of isoprenoid
      biosynthesis genes when CAS1, which encodes a key enzyme involved in the
      biosynthesis of sterols and steroidal glycoalkaloids, was down-regulated.
      Furthermore, the regulation of these genes differed among different tissues.
      These results demonstrate that our system can rapidly analyse the regulatory
      mechanisms involved in the biosynthesis of secondary metabolites.

PMID- 30287832
TI  - The endless visuomotor calibration of reach-to-grasp actions.
AB  - It is reasonable to assume that when we grasp an object we carry out the movement
      based only on the currently available sensory information. Unfortunately, our
      senses are often prone to err. Here, we show that the visuomotor system exploits
      the mismatch between the predicted and sensory outcomes of the immediately
      preceding action (sensory prediction error) to attain a degree of robustness
      against the fallibility of our perceptual processes. Participants performed reach
      to-grasp movements toward objects presented at eye level at various distances.
      Grip aperture was affected by the object distance, even though both visual
      feedback of the hand and haptic feedback were provided. Crucially, grip aperture
      as well as the trajectory of the hand were systematically influenced also by the
      immediately preceding action. These results are well predicted by a model that
      modifies an internal state of the visuomotor system by adjusting the visuomotor
      mapping based on the sensory prediction errors. In sum, the visuomotor system
      appears to be in a constant fine-tuning process which makes the generation and
      control of grasping movements more resistant to interferences caused by our
      perceptual errors.

PMID- 30287833
TI  - Ultra-low-field magneto-elastocaloric cooling in a multiferroic composite device.
AB  - The advent of caloric materials for magnetocaloric, electrocaloric, and
      elastocaloric cooling is changing the landscape of solid state cooling
      technologies with potentials for high-efficiency and environmentally friendly
      residential and commercial cooling and heat-pumping applications. Given that
      caloric materials are ferroic materials that undergo first (or second) order
      phase transitions near room temperature, they open up intriguing possibilities
      for multiferroic devices with hitherto unexplored functionalities coupling their
      thermal properties with different fields (magnetic, electric, and stress) through
      composite configurations. Here we demonstrate a magneto-elastocaloric effect with
      ultra-low magnetic field (0.16 T) in a compact geometry to generate a cooling
      temperature change as large as 4 K using a magnetostriction/superelastic alloy
      composite. Such composite systems can be used to circumvent shortcomings of
      existing technologies such as the need for high-stress actuation mechanism for
      elastocaloric materials and the high magnetic field requirement of magnetocaloric
      materials, while enabling new applications such as compact remote cooling
      devices.

PMID- 30287834
TI  - Changing environments during the Middle-Upper Palaeolithic transition in the
      eastern Cantabrian Region (Spain): direct evidence from stable isotope studies on
      ungulate bones.
AB  - Environmental change has been proposed as a factor that contributed to the
      extinction of the Neanderthals in Europe during MIS3. Currently, the different
      local environmental conditions experienced at the time when Anatomically Modern
      Humans (AMH) met Neanderthals are not well known. In the Western Pyrenees,
      particularly, in the eastern end of the Cantabrian coast of the Iberian
      Peninsula, extensive evidence of Neanderthal and subsequent AMH activity exists,
      making it an ideal area in which to explore the palaeoenvironments experienced
      and resources exploited by both human species during the Middle to Upper
      Palaeolithic transition. Red deer and horse were analysed using bone collagen
      stable isotope analysis to reconstruct environmental conditions across the
      transition. A shift in the ecological niche of horses after the Mousterian
      demonstrates a change in environment, towards more open vegetation, linked to
      wider climatic change. In the Mousterian, Aurignacian and Gravettian, high inter
      individual nitrogen ranges were observed in both herbivores. This could indicate
      that these individuals were procured from areas isotopically different in
      nitrogen. Differences in sulphur values between sites suggest some variability in
      the hunting locations exploited, reflecting the human use of different parts of
      the landscape. An alternative and complementary explanation proposed is that
      there were climatic fluctuations within the time of formation of these
      archaeological levels, as observed in pollen, marine and ice cores.

PMID- 30287835
TI  - Author Correction: Single compounds elicit complex behavioural responses in wild,
      free-ranging rats.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30287836
TI  - Earthquake-induced structural deformations enhance long-term solute fluxes from
      active volcanic systems.
AB  - Evidence for relationships between seismotectonic activity and dissolved
      weathering fluxes remains limited. Motivated by the occurrence of new springs
      emerging after the 2016 Kumamoto earthquake and supported by historical
      groundwater data, this study focuses on the long-term effect of near-surface
      structural deformation on the contribution of deep, highly saline fluids to the
      solute fluxes from the Aso caldera, Kyushu, Japan. Available hydrologic and
      structural data suggest that concentrated, over-pressured groundwaters migrate to
      the surface when new hydraulic pathways open during seismic deformation. These
      new springs have a hydrochemical fingerprint (including deltaDH2O, delta18OH2O,
      delta7Li, delta11B, delta18OSO4, and delta34SSO4) indistinguishable from long
      established confined groundwater that likely reflects a mixture of infiltrated
      meteoric water with high-sulfate hydrothermal fluids. A comparison of historical
      hydrochemistry data and patterns of past seismicity suggests that discharge of
      deep fluids is associated with similar deformation structures to those observed
      during the Kumamoto earthquake, and that seismic activity plays an important role
      over historic timescales in delivering the majority of the solutes to the caldera
      outlet, sustaining fluxes that are amongst the world's highest. This upwelling
      mechanism might be relevant for other systems too, and could contribute to the
      over-proportional share of active volcanic areas in global weathering fluxes.

PMID- 30287837
TI  - Categorical emotion recognition from voice improves during childhood and
      adolescence.
AB  - Converging evidence demonstrates that emotion processing from facial expressions
      continues to improve throughout childhood and part of adolescence. Here we
      investigated whether this is also the case for emotions conveyed by non
      linguistic vocal expressions, another key aspect of social interactions. We
      tested 225 children and adolescents (age 5-17) and 30 adults in a forced-choice
      labeling task using vocal bursts expressing four basic emotions (anger, fear,
      happiness and sadness). Mixed-model logistic regressions revealed a small but
      highly significant change with age, mainly driven by changes in the ability to
      identify anger and fear. Adult-level of performance was reached between 14 and 15
      years of age. Also, across ages, female participants obtained better scores than
      male participants, with no significant interaction between age and sex effects.
      These results expand the findings showing that affective prosody understanding
      improves during childhood; they document, for the first time, continued
      improvement in vocal affect recognition from early childhood to mid- adolescence,
      a pivotal period for social maturation.

PMID- 30287839
TI  - Structural Analysis of Inhibitor Binding to CAMKK1 Identifies Features Necessary
      for Design of Specific Inhibitors.
AB  - The calcium/calmodulin-dependent protein kinases (CAMKKs) are upstream activators
      of CAMK1 and CAMK4 signalling and have important functions in neural development,
      maintenance and signalling, as well as in other aspects of biology such as Ca2+
      signalling in the cardiovascular system. To support the development of specific
      inhibitors of CAMKKs we have determined the crystal structure of CAMKK1 with two
      ATP-competitive inhibitors. The structures reveal small but exploitable
      differences between CAMKK1 and CAMKK2, despite the high sequence identity, which
      could be used in the generation of specific inhibitors. Screening of a kinase
      inhibitor library revealed molecules that bind potently to CAMKK1. Isothermal
      titration calorimetry revealed that the most potent inhibitors had binding
      energies largely dependent on favourable enthalpy. Together, the data provide a
      foundation for future inhibitor development activities.

PMID- 30287838
TI  - Systematic expression alteration analysis of master reprogramming factor OCT4 and
      its three pseudogenes in human cancer and their prognostic outcomes.
AB  - OCT4 is a master transcription factor that regulates the pluripotency of
      pluripotent stem cells and cancer stem cells along with other factors, including
      SOX2, KLF4, and C-MYC. Three different transcripts, OCT4A, OCT4B, and OCT4B1, are
      known to be generated by alternative splicing and eight OCT4 pseudogenes have
      been found in the human genome. Among them, we examined OCT4 and three
      pseudogenes (POU5F1P1, POU5F1P3, and POU5F1P4) because of their high expression
      possibility in cancer. In addition, previous studies indicated that OCT4
      expression is augmented in cervical cancer and associated with poor prognosis,
      whereas OCT4 is down-regulated and correlated with good clinical outcomes in
      breast cancer. Because of these conflicting reports, we systematically evaluated
      whether expression of OCT4 and its pseudogenes can serve as oncogenic markers in
      various human cancers using the Oncomine database. Moreover, copy number
      alterations and mutations in OCT4 gene and its pseudogenes were analyzed using
      cBioPortal and the relationship between expression of OCT4 and pseudogenes and
      survival probability of cancer patients were explored using Kaplan-Meier plotter,
      OncoLnc, PROGgeneV2, and PrognoScan databases. Multivariate survival analysis was
      further conducted to determine the risk of the expression of the occurrence of
      OCT4 and its pseudogenes on certain cancer types using data from the Kaplan-Meier
      plotter. Overall, an association between expression of OCT4 and pseudogenes and
      cancer prognosis were established, which may serve as a therapeutic target for
      various human cancers.

PMID- 30287840
TI  - Procaspase-3-activating compound 1 stabilizes hypoxia-inducible factor 1alpha and
      induces DNA damage by sequestering ferrous iron.
AB  - Procaspase-3-activating compound 1 (PAC-1) induces procaspase-3 activation via
      zinc chelation. However, whether PAC-1 employs other mechanisms remains unknown.
      Here we systematically screened for potent PAC-1 targets using 29 enhanced green
      fluorescent protein-labeled reporter cell lines and identified hypoxia-inducible
      factor 1alpha (HIF1alpha) and RAD51 pathways as PAC-1 targets. These results were
      verified in HepG2 cells and two other cancer cell lines. Mechanistically, PAC-1
      specifically blocked HIF1alpha hydroxylation and upregulated HIF1alpha target
      genes. In addition, DNA damage, G1/S cell cycle arrest, and the inhibition of DNA
      synthesis were induced following PAC-1 administration. Interestingly, by using
      ferrozine-iron sequestration and iron titration assays, we uncovered the iron
      sequestering capacity of PAC-1. Additionally, the expression levels of iron
      shortage-related genes were also increased in PAC-1-treated cells, and iron (II)
      supplementation reversed all of the observed cellular responses. Thus, our
      results indicate that PAC-1 induces HIF1alpha stabilization and DNA damage by
      sequestering ferrous iron.

PMID- 30287842
TI  - Design, Construction and Validation of an Electrical Impedance Probe with Contact
      Force and Temperature Sensors Suitable for in-vivo Measurements.
AB  - Bioimpedance spectroscopy measurements can be used for tissue characterization.
      These measurements can be performed in soft tissues by direct contact of a non
      invasive probe consisting of two or four electrodes. The amount of force applied
      by users can be quite different, and the measurements can vary as a result. To
      compensate for this, we have built an electrical impedance probe (diameter 3.2
      mm) with fibre optic contact-force and temperature sensors built in it. The
      different sensors of the probe were tested individually. The errors in magnitude
      and phase angle of the probe are <0.9% and <4 degrees , respectively, for a 0.9%
      NaCl solution. The linear dynamic range of the force sensor was from 0 to 100
      grams. An ex-vivo experiment on a section of proximal colon from a guinea-pig was
      performed. Twenty bioimpedance measurements were taken in a frequency range of 5
      kHz to 1 MHz, while simultaneously recording the force applied. For an increase
      in contact pressure applied to tissue from 0 to 15.4 kPa, the maximum change in
      resistivity was 33% at 5 kHz and the minimum was 6.6% at 142 kHz. The probe is
      small enough to be introduced via the instrument port of an endoscope.

PMID- 30287841
TI  - Genetic inhibition of an ATP synthase subunit extends lifespan in C. elegans.
AB  - Mild inhibition of mitochondrial respiration leads to longevity. Disruption of
      mitochondrial respiratory components extends lifespan in Caenorhabditis elegans,
      but the effects appear to be complex and the underlying mechanism for lifespan
      regulation by mitochondrial respiratory genes is still not fully understood.
      Here, we investigated the role of Y82E9BR.3, a worm homolog of the ATP synthase
      subunit C, in modulating longevity in C. elegans. We found that the Y82E9BR.3
      protein is localized in mitochondria and expressed in various tissues throughout
      development. RNAi knockdown of Y82E9BR.3 extends lifespan, decreases the
      accumulation of lipofuscin, and affects various physiological processes,
      including development delay, reproduction impairment and slow behavior. Further
      tissue-specific RNAi analysis showed that the intestine is a crucial organ for
      the longevity effects conferred by Y82E9BR.3 RNAi. Moreover, we demonstrated that
      lifespan extension by Y82E9BR.3 RNAi is associated with reduced mitochondrial
      function, as well as the suppression of complex I activity in mitochondria.
      Unexpectedly, Y82E9BR.3 RNAi knock down did not influence the whole-worm ATP
      level. Our findings first reveal the crucial role of Y82E9BR.3 in mitochondrial
      function and the underlying mechanism of how Y82E9BR.3 regulates lifespan in C.
      elegans.

PMID- 30287843
TI  - A handheld platform for target protein detection and quantification using
      disposable nanopore strips.
AB  - Accessible point-of-care technologies that can provide immunoassay and molecular
      modalities could dramatically enhance diagnostics, particularly for infectious
      disease control in low-resource settings. Solid-state nanopores are simple and
      durable sensors with low-energy instrumentation requirements. While nanopore
      sensors have demonstrated efficacy for nucleic acid targets, selective detection
      and quantification of target proteins from sample background has not been
      demonstrated. We present a simple approach for electronic detection and
      quantification of target proteins that combines novel biomolecular engineering
      methods, a portable reader device and disposable nanopore test strips. The target
      of interest can be varied by swapping the binding domain on our engineered
      detection reagent, which eficiently binds in the bulk-phase to the target and
      subsequently generates a unique signature when passing through the pore. We show
      modularity of the detection reagent for two HIV antibodies, TNFalpha and tetanus
      toxin as targets. A saliva swab-to-result is demonstrated for clinically relevant
      HIV antibody levels (0.4-20 mg/liter) in under 60 seconds. While other strip-like
      assays are qualitative, the presented method is quantitative and sets the stage
      for simultaneous immunoassay and molecular diagnostic functionality within a
      single portable platform.

PMID- 30287844
TI  - A-to-I RNA editing enzyme ADAR2 regulates light-induced circadian phase-shift.
AB  - In mammals, the central circadian clock is located in the suprachiasmatic nucleus
      (SCN) of the hypothalamus and it orchestrates peripheral clocks in the whole body
      to organize physiological and behavioral rhythms. Light-induced phase-shift of
      the SCN clock enables synchronization of the circadian clock system with 24-h
      environmental light/dark cycle. We previously found that adenosine deaminase
      acting on RNA 2 (Adar2), an A-to-I RNA editing enzyme catalyzing rhythmic A-to-I
      RNA editing, governs a wide range of mRNA rhythms in the mouse liver and
      regulates the circadian behavior. In brain, ADAR2-mediated A-to-I RNA editing was
      reported to occur in various transcripts encoding ion channels and
      neurotransmitter receptors, which could influence neuronal function of the SCN.
      Here we show that ADAR2 plays a crucial role for light-induced phase-shift of the
      circadian clock. Intriguingly, exposure of Adar2-knockout mice to a light pulse
      at late night caused an aberrant phase-advance of the locomotor rhythms. By
      monitoring the bioluminescence rhythms of the mutant SCN slices, we found that a
      phase-advance induced by treatment with pituitary adenylyl cyclase-activating
      polypeptide (PACAP) was markedly attenuated. The present study suggests that A-to
      I RNA editing in the SCN regulates a proper phase response to light in the mouse
      circadian system.

PMID- 30287845
TI  - A Next-Generation Sequencing-Based Platform for Quantitative Detection of
      Hepatitis B Virus Pre-S Mutants in Plasma of Hepatocellular Carcinoma Patients.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death
      worldwide. Early diagnosis and treatment of HCC remain a key goal for improving
      patient survival. Chronic hepatitis B virus (HBV) infection is a major risk
      factor for HCC development. Pre-S mutants harboring deletions in HBV large
      surface antigen have been well demonstrated as HBV oncoproteins that dysregulate
      multiple signaling pathways in hepatocytes, leading to HCC formation. The
      presence of pre-S mutants in plasma represents important predictive and
      prognostic markers for HCC in patients with chronic HBV infection. However, the
      method to detect pre-S mutants remains to be optimized. In this study, we
      developed a platform, based on the next-generation sequencing (NGS) technology,
      for detection of pre-S mutants in plasma of HBV-related HCC patients. Compared to
      the current TA cloning-based analysis, the NGS-based analysis could detect pre-S
      deletion quantitatively, and the detection rate was significantly more sensitive
      in 49 plasma analyzed (McNemar's paired proportion test, P value < 0.0001; simple
      kappa coefficient, kappa = 0.29 (95% CI, 0.12 to 0.46)). Our data suggest that
      the NGS-based platform may hold a promise for improving the clinical application
      of pre-S mutants in serving as predictive and prognostic markers for HBV-related
      HCC.

PMID- 30287846
TI  - Drivers of within-field spatial and temporal variability of crop yield across the
      US Midwest.
AB  - Not all areas of a farmer's field are equal; some always produce more relative to
      the rest of the field, others always less, while still other areas fluctuate in
      their production capacity from one year to the next, depending on the interaction
      between climate, soil, topography and management. Understanding why the yield in
      certain portions of a field has a high variability over time-we call these areas
      unstable-is of paramount importance both from an economic and an environmental
      point of view, as it is through the better management of these areas that we can
      improve yields or reduce input costs and environmental impact. In this research,
      we analyzed data from 338 fields cultivated with maize, soybean, wheat and cotton
      in the US Midwest to understand how topographic attributes and rain affect yield
      stability over time. In addition to this high resolution yield monitor dataset,
      we used publicly available data on topography, rain and soil information to test
      the hypothesis that within-field areas characterized by a low topographic wetness
      index (proxy for areas with probability of lower water content) always perform
      poorly (low and stable yield) compared to the rest of the field because they are
      drier, and that areas of a field characterized by a mid-high wetness index (high
      and stable yield) always perform well relative to rest of the field because they
      have greater water availability to plants. The relative performance of areas of a
      field with a very high wetness index (e.g. depressions) strongly depends on rain
      patterns because they may be waterlogged in wet years, yielding less than the
      rest of the field, or wetter during dry years, yielding more than the rest of the
      field. We present three different observations from this dataset to support our
      hypothesis. First, we show that the average topographic wetness index in the
      different stability zones is lower in low and stable yield areas, high in high
      and stable yield areas and even higher in unstable yield areas (p < 0.05).
      Second, we show that in dry years (low precipitation at plant emergence or in
      July), unstable zones perform relatively better compared to the rest of the
      field. Third, we show that temporal yield variability is positively correlated (p
      < 0.05) with the probability of observing gleying processes associated with
      waterlogging for part of the year. These findings shed light on mechanisms
      underlying temporal variability of yield and can help guide management solutions
      to increase profit and improve environmental quality.

PMID- 30287847
TI  - Comparative synaptosome imaging: a semi-quantitative method to obtain copy
      numbers for synaptic and neuronal proteins.
AB  - Protein copy numbers can be measured by biochemical methods ranging from
      quantitative Western Blotting to several mass spectrometry approaches. Such
      methods only provide average copy numbers, obtained over large cell numbers.
      However, copy number estimates for single cells or single organelles could be
      obtained by combining biochemical characterizations with an imaging approach. We
      performed this here for synaptic proteins, in a protocol that we termed
      comparative synaptosome imaging for semi-quantitative copy numbers (CosiQuant).
      In brief, in CosiQuant we immunostain in parallel biochemically-characterized
      synaptosomes, for which we have already determined the average protein copy
      numbers, and the samples of interest (such as neuronal cultures). We then derive
      the copy numbers in the samples of interest by comparing the immunofluorescence
      intensities. We measured the intensities not only in arbitrary fluorescence
      units, but also as numbers of antibodies per synaptosome, for a large number of
      targets. This implies that other groups can immediately apply CosiQuant for these
      targets, by simply estimating the number of antibodies per structure of interest.
      CosiQuant should therefore be a useful addition to the growing set of imaging
      techniques for synaptic neuroscience.

PMID- 30287848
TI  - Experimental evidence of selective inattention in reputation-based cooperation.
AB  - Reputation-based cooperation is often observed in modern society. People gain
      several types of information by assessing others. Among these, the most important
      information is the actions of people and those of their recipients. However,
      almost all studies assume that people consider all of the information they
      receive. This assumption is extreme, and people engaging in reputation-based
      cooperation may not pay attention to some information, i.e., they may display
      selective inattention. We demonstrate that subjects' decision-making in relation
      to cooperative action depends on the content of the information they receive
      about their recipients. Our results show that subjects either consider or ignore
      information depending on the content of that information. When their recipients
      had cooperated previously, subjects cooperated without considering the
      information they received. When the recipients had played before with those who
      had bad reputations, subjects did not use that information, regardless of whether
      it was disclosed proactively. In other cases, subjects considered information on
      both the previous actions of recipients and those of the recipients' own
      recipients. We found that subjects did not always use the information to make
      decisions, although they willingly received information about their recipients.
      This supports the proposition that selective inattention occurs in reputation
      based cooperation.

PMID- 30287849
TI  - Computational Analysis of topological indices of two Boron Nanotubes.
AB  - There has been a recent debate that boron nanotubes can outperform carbon
      nanotubes on many grounds. The most stable boron nanotubes are made of a
      hexagonal lattice with an extra atom added to some of the hexagons called ?-boron
      nanotubes. Closed forms of M-polynomial of nanotubes produce closed forms of many
      degree-based topological indices which are numerical parameters of the structure
      and determine physico-chemical properties of the concerned nanotubes. In this
      article, we compute and analyze many topological indices of ?-boron nanotubes
      correlating with the size of structure of these tubes through the use of M
      polynomial. More importantly we make a graph-theoretic comparison of indices of
      two types of boron nanotubes namely triangular boron and ?-boron nanotubes.

PMID- 30287850
TI  - A subtype of cancer-associated fibroblasts with lower expression of alpha-smooth
      muscle actin suppresses stemness through BMP4 in oral carcinoma.
AB  - Cancer-associated fibroblasts (CAFs) demonstrate the characteristics of
      myofibroblast differentiation by often expressing the ultrastructure of alpha
      smooth muscle actin (alphaSMA). However, heterogeneity among cancer-associated
      fibroblasts (CAFs), with respect to alphaSMA expression, has been demonstrated in
      several clinical studies of oral cancer. Like normal stem cells, stem-like cancer
      cells (SLCCs) are also regulated extrinsically by its microenvironment;
      therefore, we postulated that the heterogeneous oral-CAFs would differently
      regulate oral-SLCCs. Using transcriptomics, we clearly demonstrated that the gene
      expression differences between oral tumor-derived CAFs were indeed the molecular
      basis of heterogeneity. This also grouped these CAFs in two distinct clusters,
      which were named as C1 and C2. Interestingly, the oral-CAFs belonging to C1 or C2
      clusters showed low or high alphaSMA-score, respectively. Our data with tumor
      tissues and in vitro co-culture experiments interestingly demonstrated a negative
      correlation between alphaSMA-score and cell proliferation, whereas, the frequency
      of oral-SLCCs was significantly positively correlated with alphaSMA-score. The
      oral-CAF-subtype with lower score for alphaSMA (C1-type CAFs) was more supportive
      for cell proliferation but suppressive for the self-renewal growth of oral-SLCCs.
      Further, we found the determining role of BMP4 in C1-type CAFs-mediated
      suppression of self-renewal of oral-SLCCs. Overall, we have discovered an
      unexplored interaction between CAFs with lower-alphaSMA expression and SLCCs in
      oral tumors and provided the first evidence about the involvement of CAF
      expressed BMP4 in regulation of self-renewal of oral-SLCCs.

PMID- 30287851
TI  - Cell-based chemical fingerprinting identifies telomeres and lamin A as modifiers
      of DNA damage response in cancer cells.
AB  - Telomere maintenance by telomerase activity supports the infinite growth of
      cancer cells. MST-312, a synthetic telomerase inhibitor, gradually shortens
      telomeres at non-acute lethal doses and eventually induces senescence and
      apoptosis of telomerase-positive cancer cells. Here we report that MST-312 at
      higher doses works as a dual inhibitor of telomerase and DNA topoisomerase II and
      exhibits acute anti-proliferative effects on cancer cells and xenografted tumours
      in vivo. Our cell-based chemical fingerprinting approach revealed that cancer
      cells with shorter telomeres and lower expression of lamin A, a nuclear
      architectural protein, exhibited higher sensitivity to the acute deleterious
      effects of MST-312, accompanied by formation of telomere dysfunction-induced foci
      and DNA double-strand breaks. Telomere elongation and lamin A overexpression
      attenuated telomeric and non-telomeric DNA damage, respectively, and both
      conferred resistance to apoptosis induced by MST-312 and other DNA damaging
      anticancer agents. These observations suggest that sufficient pools of telomeres
      and a nuclear lamina component contribute to the cellular robustness against DNA
      damage induced by therapeutic treatment in human cancer cells.

PMID- 30287852
TI  - Increased spatial and temporal autocorrelation of temperature under climate
      change.
AB  - Understanding spatiotemporal variation in environmental conditions is important
      to determine how climate change will impact ecological communities. The spatial
      and temporal autocorrelation of temperature can have strong impacts on community
      structure and persistence by increasing the duration and the magnitude of
      unfavorable conditions in sink populations and disrupting spatial rescue effects
      by synchronizing spatially segregated populations. Although increases in spatial
      and temporal autocorrelation of temperature have been documented in historical
      data, little is known about how climate change will impact these trends. We
      examined daily air temperature data from 21 General Circulation Models under the
      business-as-usual carbon emission scenario to quantify patterns of spatial and
      temporal autocorrelation between 1871 and 2099. Although both spatial and
      temporal autocorrelation increased over time, there was significant regional
      variation in the temporal autocorrelation trends. Additionally, we found a
      consistent breakpoint in the relationship between spatial autocorrelation and
      time around the year 2030, indicating an acceleration in the rate of increase of
      the spatial autocorrelation over the second half of the 21st century. Overall,
      our results suggest that ecological populations might experience elevated
      extinction risk under climate change because increased spatial and temporal
      autocorrelation of temperature is expected to erode both spatial and temporal
      refugia.

PMID- 30287853
TI  - Calcineurin B homologous protein 3 binds with high affinity to the CHP binding
      domain of the human sodium/proton exchanger NHE1.
AB  - The Na+/H+ exchanger NHE1 is critical for cell vitality as it controls
      intracellular pH and cell volume. Its functionality is influenced by calcineurin
      B homologous proteins (CHPs). The human isoform CHP3 is important for transport
      of NHE1 to the plasma membrane and for its activity. Here, we characterized the
      binding interaction of human CHP3 with the regulatory domain of NHE1. The exact
      binding site of CHP3 was previously debated. CHP3 as well as both regions of NHE1
      in question were produced and purified. CHP3 specifically formed stable complexes
      with the CHP-binding region (CBD) of NHE1 (residues 503-545) in size-exclusion
      chromatography (SEC), but not with the C-terminal region (CTD, residues 633-815).
      CTD was functional as shown by Ca2+-dependent binding of calmodulin in SEC
      analysis. CHP3 bound with high affinity to CBD with an equilibrium dissociation
      constant (KD) of 56 nM determined by microscale thermophoresis. The high affinity
      was substantiated by isothermal calorimetry analysis (KD = 3 nM), which also
      revealed that the interaction with CBD is strongly exothermic (DeltaG degrees  = 
      48.6 kJ/mol, DeltaH = -75.3 kJ/mol, -TDeltaS degrees  = 26.7 kJ/mol). The data
      provide insights in the molecular mechanisms that underlie the regulatory
      interaction of CHP3 and NHE1 and more general of calcineurin homologous proteins
      with their target proteins.

PMID- 30287854
TI  - Quantum Artificial Life in an IBM Quantum Computer.
AB  - We present the first experimental realization of a quantum artificial life
      algorithm in a quantum computer. The quantum biomimetic protocol encodes tailored
      quantum behaviors belonging to living systems, namely, self-replication,
      mutation, interaction between individuals, and death, into the cloud quantum
      computer IBM ibmqx4. In this experiment, entanglement spreads throughout
      generations of individuals, where genuine quantum information features are
      inherited through genealogical networks. As a pioneering proof-of-principle,
      experimental data fits the ideal model with accuracy. Thereafter, these and other
      models of quantum artificial life, for which no classical device may predict its
      quantum supremacy evolution, can be further explored in novel generations of
      quantum computers. Quantum biomimetics, quantum machine learning, and quantum
      artificial intelligence will move forward hand in hand through more elaborate
      levels of quantum complexity.

PMID- 30287855
TI  - Ropeginterferon alpha-2b targets JAK2V617F-positive polycythemia vera cells in
      vitro and in vivo.
AB  - Polycythemia vera is characterized by the acquisition of the JAK2V617F mutation.
      Recommended treatments include hydroxyurea and interferon-alpha. Several groups
      have reported a reduction in the JAK2 mutant allele burden in interferon-treated
      patients, but significance of this observation is questioned. We characterized
      the activity of ropeginterferon alpha-2b, a novel form of interferon-alpha
      recently shown to be safe and efficacious in polycythemia vera. Ropeginterferon
      was able to inhibit the proliferation of the HEL, UKE-1, and UT-7 JAK2-mutant
      cell lines while sparing JAK2-wild-type UT-7 and normal CD34+ cells growth. In
      vitro treatment of erythroid progenitors derived from PV patients showed that
      ropeginterferon could considerably inhibit the growth of endogenous erythroid
      colonies, a hallmark of polycythemia vera. Finally, we could study in sequential
      samples the clonal architecture of erythroid progenitors derived from patients
      included in a randomized study comparing hydroxyurea to ropeginterferon. After 1
      year of treatment with ropeginterferon, the ratio of JAK2-mutated to wild-type
      colonies grown from bone marrow progenitors was reduced by 64%, compared to 25%
      in patients receiving hydroxyurea. This study shows that ropeginterferon has a
      potent targeted activity against JAK2-mutant cells and is able to drastically
      reduce the proportion of malignant progenitors in patients treated with this
      drug.

PMID- 30287857
TI  - Self-triggered Asynchronous Optical Sampling Terahertz Spectroscopy using a
      Bidirectional Mode-locked Fiber Laser.
AB  - We report a self-triggered asynchronous optical sampling terahertz spectroscopy
      system based on a single bidirectional mode-locked fiber laser and plasmonics
      enhanced photoconductive nanoantennas. The fiber laser generates two optical
      mutually coherent pulse trains with a stable repetition rate difference, enabling
      time-domain terahertz spectroscopy without using any mechanical delay line,
      stabilization electronics, or external trigger. The resolved terahertz spectra
      over a 0.1-2 THz frequency range and a 30-second measurement time show more than
      a 70-dB dynamic range, revealing water absorption lines matching the HITRAN
      database, through a light-weight and compact spectroscopy setup.

PMID- 30287856
TI  - Genome-wide association study identifies two risk loci for tuberculosis in Han
      Chinese.
AB  - Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis
      (Mtb), and remains a leading public health problem. Previous studies have
      identified host genetic factors that contribute to Mtb infection outcomes.
      However, much of the heritability in TB remains unaccounted for and additional
      susceptibility loci most likely exist. We perform a multistage genome-wide
      association study on 2949 pulmonary TB patients and 5090 healthy controls (833
      cases and 1220 controls were genome-wide genotyped) from Han Chinese population.
      We discover two risk loci: 14q24.3 (rs12437118, Pcombined = 1.72 * 10-11, OR =
      1.277, ESRRB) and 20p13 (rs6114027, Pcombined = 2.37 * 10-11, OR = 1.339, TGM6).
      Moreover, we determine that the rs6114027 risk allele is related to decreased
      TGM6 transcripts in PBMCs from pulmonary TB patients and severer pulmonary TB
      disease. Furthermore, we find that tgm6-deficient mice are more susceptible to
      Mtb infection. Our results provide new insights into the genetic etiology of TB.

PMID- 30287858
TI  - Leptin Increases Particle-Induced Osteolysis in Female ob/ob Mice.
AB  - Particles generated from wear of prosthesis joint bearing surfaces induce
      inflammation-mediated periprosthetic bone resorption (osteolysis). Morbidly obese
      leptin-deficient ob/ob mice are resistant to polyethylene particle-induced bone
      loss, suggesting that leptin, a hormone produced by adipocytes that circulates in
      concentrations proportional to total body adiposity, increases osteolysis. To
      confirm that particles induce less osteolysis in leptin-deficient mice after
      controlling for cold stress (room temperature)-induced bone loss, ob/ob mice on a
      C57BL/6 (B6) background and colony B6 wildtype (WT) mice housed at thermoneutral
      temperature were randomized to control or particle treatment groups (N =
      5/group). Polyethylene particles were implanted over calvaria and mice sacrificed
      2 weeks later. Compared to particle-treated WT mice, particle-treated ob/ob mice
      had lower osteolysis score, less infiltration of immune cells, and less woven
      bone formation. To determine the role of leptin in particle-induced osteolysis,
      ob/ob mice were randomized into one of 4 groups (n = 6-8/group): (1) control, (2)
      particles, (3) particles + continuous leptin (osmotic pump, 6 MUg/d), or (4)
      particles + intermittent leptin (daily injection, 40 MUg/d). Leptin treatment
      increased particle-induced osteolysis in ob/ob mice, providing evidence that the
      adpiokine may play a role in inflammation-driven bone loss. Additional research
      is required to determine whether altering leptin levels within the physiological
      range results in corresponding changes in polyethylene-particle-induced
      osteolysis.

PMID- 30287859
TI  - Risk of Incident Cardiovascular Disease and Cardiovascular Risk Factors in First
      and Second-Generation Indians: The Singapore Indian Eye Study.
AB  - Population-based data investigating generational differences in the risk of
      incident cardiovascular disease (CVD) and its risk determinants are rare. We
      examined the 6-year incidence of CVD and its risk factors in first- and second
      generation ethnic Indians living in Singapore. 1749 participants (mean age [SD]:
      55.5 [8.8] years; 47.5% male) from a population-based, longitudinal study of
      Indian adults were included for incident CVD outcome. Incident CVD was defined as
      self-reported myocardial infarction, angina pectoris or stroke which developed
      between baseline and follow-up. CVD-related risk factors included incident
      diabetes, hypertension, hyperlipidemia, obesity and chronic kidney disease (CKD).
      For incident CVD outcome, of the 1749 participants, 406 (23.2%) and 1343 (76.8%)
      were first and second-generation Indians, respectively. Of these, 73 (4.1%)
      reported incident CVD. In multivariable models, second-generation individuals had
      increased risk of developing CVD (RR = 2.04; 95% CI 1.04, 3.99; p = 0.038),
      hyperlipidemia (RR = 1.27; 95% CI 1.06, 1.53; p = 0.011), and CKD (RR = 1.92; 95%
      CI 1.22, 3.04; p = 0.005), compared to first-generation Indians. Second
      generation Indians have increased risk of developing CVD and its associated risk
      factors such as hyperlipidemia and CKD compared to first-generation immigrants,
      independent of traditional CVD risk factors. More stratified and tailored CVD
      prevention strategies on second and subsequent generations of Indian immigrants
      in Singapore are warranted.

PMID- 30287860
TI  - Genome-wide analysis of horizontally acquired genes in the genus Mycobacterium.
AB  - Horizontal gene transfer (HGT) was attributed as a major driving force for the
      innovation and evolution of prokaryotic genomes. Previously, multiple research
      endeavors were undertaken to decipher HGT in different bacterial lineages. The
      genus Mycobacterium houses some of the most deadly human pathogens; however, the
      impact of HGT in Mycobacterium has never been addressed in a systematic way.
      Previous initiatives to explore the genomic imprints of HGTs in Mycobacterium
      were focused on few selected species, specifically among the members of
      Mycobacterium tuberculosis complex. Considering the recent availability of a
      large number of genomes, the current study was initiated to decipher the probable
      events of HGTs among 109 completely sequenced Mycobacterium species. Our
      comprehensive phylogenetic analysis with more than 9,000 families of
      Mycobacterium proteins allowed us to list several instances of gene transfers
      spread across the Mycobacterium phylogeny. Moreover, by examining the topology of
      gene phylogenies here, we identified the species most likely to donate and
      receive these genes and provided a detailed overview of the putative functions
      these genes may be involved in. Our study suggested that horizontally acquired
      foreign genes had played an enduring role in the evolution of Mycobacterium
      genomes and have contributed to their metabolic versatility and pathogenicity.

PMID- 30287861
TI  - Preparation of cationized gelatin nanospheres incorporating molecular beacon to
      visualize cell apoptosis.
AB  - The objective of this study is to prepare cationized gelatin nanospheres (cGNS)
      incorporating a molecular beacon (MB), and visualize cellular apoptosis. Two
      types of MB to detect the messenger RNA (mRNA) of glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) (GAP MB), and caspase-3 (casp3 MB) were incorporated in
      cGNS, respectively. MB incorporated in cGNS showed the DNA sequence specificity
      in hybridization. The cGNS incorporation enabled MB to enhance the stability
      against nuclease to a significantly great extent compared with free MB. The cGNS
      incorporating GAP MB were internalized into the KUM6 of a mouse bone marrow
      derived stem cell by an endocytotic pathway. The cGNS were not distributed at the
      lysosomes. After the incubation with cGNS, the cell apoptosis was induced at
      different concentrations of camptothecin. No change in the intracellular
      fluorescence was observed for cGNSGAPMB. On the other hand, for the cGNScasp3MB,
      the fluorescent intensity significantly enhanced by the apoptosis induction of
      cells. It is concluded that cGNS incorporating MB is a promising system for the
      visualization of cellular apoptosis.

PMID- 30287862
TI  - Experimental Observation of the High Pressure Induced Substitutional Solid
      Solution and Phase Transformation in Sb2S3.
AB  - The substitutional solid solutions composed of group VA-VIA nonmetallic elements
      has attracted considerable scientific interest since they provide a pressure
      induced route to search for novel types of solid solutions with potential
      applications. Yet, the pressure-induced solid solution phase is unprecedented in
      the sulfide family. In this paper, the structural behavior of antimony
      trisulfide, Sb2S3, has been investigated in order to testify whether or not it
      can also be driven into the substitutional solid solution phase by high
      pressures. The experiments were carried out by using a diamond anvil cell and
      angle dispersive synchrotron X-ray diffraction up to 50.2 GPa at room
      temperature. The experimental results indicate that Sb2S3 undergoes a series of
      phase transitions at 5.0, 12.6, 16.9, 21.3, and 28.2 GPa, and develops ultimately
      into an Sb-S substitutional solid solution, which adopts a body-centered cubic
      disordered structure. In this structure, the Sb and S atoms are distributed
      randomly on the bcc lattice sites with space group Im-3m. The structural behavior
      of Sb2S3 is tentatively assigned by comparison within the A2B3 (A = Sb, Bi; B =
      Se, Te, S) series under high pressures.

PMID- 30287863
TI  - Positive Caricature Transcriptomic Effects Associated with Broad Genomic
      Aberrations in Colorectal Cancer.
AB  - We re-examined the correlation between Broad Genomic Aberrations (BGAs) and
      transcriptomic profiles in Colorectal Cancer (CRC). Two types of BGAs have been
      examined: Broad Copy-Number Abnormal regions (BCNAs), distinguished in gain- and
      loss-type, and Copy-Neutral Loss of Heterozygosities (CNLOHs). Transcripts are
      classified as "OverT" or "UnderT" if overexpressed or underexpressed comparing
      CRCs bearing a specific BGA to CRCs not bearing it and as "UpT" or "DownT" if
      upregulated or downregulated in cancer compared to normal tissue. BGA-associated
      effects were evaluated by changes in the "Chromosomal Distribution Index" (CDI)
      of different transcript classes. Data show that UpT are more sensitive than DownT
      to BCNA-associated gene dosage effects. "Over-UpT" genes are upregulated in
      cancer and further overexpressed by gene dosage, defining the so called "positive
      caricature transcriptomic effect". When Over-UpT genes are ranked according to
      overexpression, top positions are occupied by genes implicated at the functional
      and therapeutic level in CRC. We show that cancer-upregulated transcripts are
      sensitive markers of BCNA-induced effects and suggest that analysis of positive
      caricature transcriptomic effects can provide clues toward the identification of
      BCNA-associated cancer driver genes.

PMID- 30287864
TI  - Potential identification of vitamin B6 responsiveness in autism spectrum disorder
      utilizing phenotype variables and machine learning methods.
AB  - We investigated whether machine learning methods could potentially identify a
      subgroup of persons with autism spectrum disorder (ASD) who show vitamin B6
      responsiveness by selected phenotype variables. We analyzed the existing data
      from our intervention study with 17 persons. First, we focused on signs and
      biomarkers that have been identified as candidates for vitamin B6 responsiveness
      indicators. Second, we conducted hypothesis testing among these selected
      variables and their combinations. Finally, we further investigated the results by
      conducting cluster analyses with two different algorithms, affinity propagation
      and k-medoids. Statistically significant variables for vitamin B6 responsiveness,
      including combination of hypersensitivity to sound and clumsiness, and plasma
      glutamine level, were included. As an a priori variable, the Pervasive
      Developmental Disorders Autism Society Japan Rating Scale (PARS) scores was also
      included. The affinity propagation analysis showed good classification of three
      potential vitamin B6-responsive persons with ASD. The k-medoids analysis also
      showed good classification. To our knowledge, this is the first study to attempt
      to identify subgroup of persons with ASD who show specific treatment
      responsiveness using selected phenotype variables. We applied machine learning
      methods to further investigate these variables' ability to identify this subgroup
      of ASD, even when only a small sample size was available.

PMID- 30287865
TI  - Genome-wide association study reveals novel genetic locus associated with intra
      individual variability in response time.
AB  - Intra-individual response time variability (IIRTV) is proposed as a viable
      endophenotype for many psychiatric disorders, particularly attention-deficit
      hyperactivity disorder (ADHD). Here we assessed whether IIRTV was associated with
      common DNA variation genome-wide and whether IIRTV mediated the relationship
      between any associated loci and self-reported ADHD symptoms. A final data set
      from 857 Australian young adults (489 females and 368 males; Mage = 22.14 years,
      SDage = 4.82 years) who completed five response time tasks and self-reported
      symptoms of ADHD using the Conners' Adult ADHD Rating Scale was used. Principal
      components analysis (PCA) on these response time measures (standard deviation of
      reaction times and the intra-individual coefficient of variation) produced two
      variability factors (labelled response selection and selective attention). To
      understand the genetic drivers of IIRTV we performed a genome-wide association
      analysis (GWAS) on these PCA-derived indices of IIRTV. For the selective
      attention variability factor, we identified one single-nucleotide polymorphism
      (SNP) attaining genome-wide significance; rs62182100 in the HDAC4 gene located on
      chromosome 2q37. A bootstrapping mediation analysis demonstrated that the
      selective attention variability factor mediated the relationship between
      rs62182100 and self-reported ADHD symptoms. Our findings provide the first
      evidence of a genome-wide significant SNP association with IIRTV and support the
      potential utility of IIRTV as a valid endophenotype for ADHD symptoms. However,
      limitations of this study suggest that these observations should be interpreted
      with caution until replication samples become available.

PMID- 30287867
TI  - Long noncoding RNA Meg3 regulates cardiomyocyte apoptosis in myocardial
      infarction.
AB  - Myocardial infarction (MI), with a major process of cardiomyocyte death, remains
      a leading cause of morbidity and mortality worldwide. To date, it has been shown
      that lncRNAs play important roles in cardiovascular pathology. However, the
      detailed studies on lncRNAs regulating cardiomyocyte death in myocardial
      infarction are still limited. In this study, we found a progressively upregulated
      expression of Meg3 in mouse injured heart after MI. Gain-of-function and loss-of
      function approaches further revealed pro-apoptotic functions of Meg3 in rodent
      cardiomyocytes. Moreover, Meg3 was directly upregulated by p53 in hypoxic
      condition, and involved in apoptotic regulation via its direct binding with RNA
      binding protein FUS (fused in sarcoma). Afterwards, adult MI mice that underwent
      intramyocardial injection with adeno-associated virus serotype 9 (AAV9) system
      carrying Meg3 shRNA showed a significant improvement of cardiac function.
      Moreover, we also found that MEG3 was increased in clinical heart failure
      samples, and had conservatively pro-apoptotic function in human cardiomyocytes
      that were differentiated from the human embryonic stem cells. Together, these
      results indicate that p53-induced Meg3-FUS complex plays an important role in
      cardiomyocyte apoptosis post-MI, and its specific knockdown in cardiomyocytes
      with AAV9 system represents a promising method to treat MI for preclinical
      investigation.

PMID- 30287869
TI  - Improving carrier mobility of polycrystalline Ge by Sn doping.
AB  - To improve the performance of electronic devices, extensive research efforts have
      recently focused on the effect of incorporating Sn into Ge. In the present work,
      we investigate how Sn composition x (0 <= x <= 0.12) and deposition temperature
      Td (50 <= Td <= 200  degrees C) of the Ge1-xSnx precursor affect subsequent solid
      phase crystallization. Upon incorporating 3.2% Sn, which is slightly above the
      solubility limit of Sn in Ge, the crystal grain size increases and the grain
      boundary barrier decreases, which increases the hole mobility from 80 to 250
      cm2/V s. Furthermore, at Td = 125  degrees C, the hole mobility reaches 380 cm2/V
      s, which is tentatively attributed to the formation of a dense amorphous GeSn
      precursor. This is the highest hole mobility for semiconductor thin films on
      insulators formed below 500  degrees C. These results thus demonstrate the
      usefulness of Sn doping of polycrystalline Ge and the importance of temperature
      while incorporating Sn. These findings make it possible to fabricate advanced Ge
      based devices including high-speed thin-film transistors.

PMID- 30287868
TI  - Continuous theta-burst stimulation over the dorsolateral prefrontal cortex
      inhibits improvement on a working memory task.
AB  - Theta-burst stimulation (TBS) over the dorsolateral prefrontal cortex (DLPFC) may
      be more effective for modulating cortical excitability compared to standard
      repetitive transcranial magnetic stimulation. However, the impact of intermittent
      (iTBS) and continuous TBS (cTBS) on working memory (WM) is poorly studied. The
      aim of our study was to compare the effects of iTBS and cTBS on WM over the left
      and right DLPFC. iTBS, cTBS or sham stimulation was administered over the right
      and left hemisphere of fifty-one healthy human subjects. WM was assessed before
      and after TBS using the 1-back, 2-back, and 3-back tasks. We found classical
      practice effects in the iTBS and the sham group: WM performance improved
      following stimulation as measured by the discriminability index. However, this
      effect could not be observed in the cTBS group. We did not find any hemisphere
      dependent effects, suggesting that the practice effect is not lateralized, and
      TBS affects WM performance in a comparable manner if administered either over the
      left or the right hemisphere. We propose that our findings represent a useful
      addition to the literature of TBS-induced effects on WM. Moreover, these results
      indicate the possibility of clarifying processes underlying WM performance
      changes by using non-invasive brain stimulation.

PMID- 30287866
TI  - Large-scale transcriptome-wide association study identifies new prostate cancer
      risk regions.
AB  - Although genome-wide association studies (GWAS) for prostate cancer (PrCa) have
      identified more than 100 risk regions, most of the risk genes at these regions
      remain largely unknown. Here we integrate the largest PrCa GWAS (N = 142,392)
      with gene expression measured in 45 tissues (N = 4458), including normal and
      tumor prostate, to perform a multi-tissue transcriptome-wide association study
      (TWAS) for PrCa. We identify 217 genes at 84 independent 1 Mb regions associated
      with PrCa risk, 9 of which are regions with no genome-wide significant SNP within
      2 Mb. 23 genes are significant in TWAS only for alternative splicing models in
      prostate tumor thus supporting the hypothesis of splicing driving risk for
      continued oncogenesis. Finally, we use a Bayesian probabilistic approach to
      estimate credible sets of genes containing the causal gene at a pre-defined
      level; this reduced the list of 217 associations to 109 genes in the 90% credible
      set. Overall, our findings highlight the power of integrating expression with
      PrCa GWAS to identify novel risk loci and prioritize putative causal genes at
      known risk loci.

PMID- 30287870
TI  - Serum GFAP as a biomarker for disease severity in multiple sclerosis.
AB  - While neurofilament light chain (NfL) measurement in serum is a well-established
      marker of neuroaxonal damage in multiple sclerosis (MS), data on astroglial
      markers in serum are missing. In our study, glial fibrillary acid protein (GFAP)
      and NfL were measured in cerebrospinal fluid (CSF) and serum of MS patients and
      patients with other non-inflammatory neurological diseases (OND) using the Simoa
      technology. Clinical data like age, gender, expanded disability status scale
      (EDSS) and MRI findings were correlated to neurochemical markers. We included 80
      MS patients: 42 relapsing-remitting MS (RRMS), 38 progressive MS (PMS), as well
      as 20 OND. Serum GFAP levels were higher in PMS compared to RRMS and OND (p <
      0.001, p = 0.02 respectively). Serum GFAP levels correlated with disease severity
      in the whole MS group and PMS (Spearman-rho = 0.5, p < 0.001 in both groups).
      Serum GFAP correlated with serum NfL in PMS patients (Spearman-rho = 0.4, p =
      0.01). Levels of serum GFAP were higher with increasing MRI-lesion count (p =
      0.01). in summary, we report elevated levels of GFAP in the serum of MS patients.
      Since serum levels of GFAP correlate with the clinical severity scores and MRI
      lesion count, especially in PMS patients, it might be a suitable disease
      progression marker.

PMID- 30287871
TI  - Risk assessment of prolonged jaundice in infants at one month of age: A
      prospective cohort study.
AB  - Prolonged jaundice is a commonly evaluated condition. The aim of this study was
      to assess the risk factors of jaundice in healthy infants at one month of age.
      This prospective cohort study enrolled 509 healthy infants from 2013 to 2018.
      Those with gestational age (GA) less than 35 weeks, birth weight less than 2000
      grams, and illness were not enrolled. Jaundice was defined as a transcutaneous
      bilirubin value >=5 mg/dL at 25-45 days of age. Umbilical cord blood samples were
      obtained to examine seven common gene variants. The incidence of prolonged
      jaundice was 32.2%. Prolonged jaundice was more common in infants with exclusive
      breastfeeding (p < 0.001), GA 35~37 w (p = 0.001), stool passage >4 times/d (p <
      0.001), previous phototherapy (p < 0.001), and gene variant of G to A at nt 211
      of UGT1A1 (p = 0.004). A multivariate logistic regression analysis demonstrated
      the greatest risk for prolonged jaundice was exclusive breastfeeding (OR = 2.818,
      95% CI = 1.851-4.292), followed by previous phototherapy (OR = 2.593, 95% CI =
      1.716-3.919), GA 35~37 w (OR = 2.468, 95% CI = 1.350-4.512), and G to A at nt 211
      of UGT1A1 (OR = 1.645, 95% CI = 1.070-2.528). In conclusion, infants with
      exclusive breastfeeding, GA 35~37 w, previous phototherapy, or G to A at nt 211
      of UGT1A1 are at greater risk of prolonged jaundice. Healthcare professionals
      should consider these risk factors in their assessment of prolonged jaundice.

PMID- 30287872
TI  - Correction: Evidence-based scientific exercise guidelines for adults with spinal
      cord injury: an update and a new guideline.
AB  - Authors Victoria L. Goosey-Tolfrey and Karen M. Smith were listed under the
      incorrect affiliations at the time of publication.

PMID- 30287874
TI  - Direct Thermal Growth of Large Scale Cl-doped CdTe Film for Low Voltage High
      Resolution X-ray Image Sensor.
AB  - Polycrystalline cadmium telluride (CdTe) X-ray photodetector with advanced
      performance was fabricated in a Schottky diode form by direct thermal deposition
      (evaporation) on pixelized complementary metal oxide semiconductor (CMOS) readout
      panel. Our CdTe X-ray detector shows such a variety of benefits as relatively low
      process temperature, low cost, low operation voltage less than 40 V, and higher
      sensitivity and spatial resolution than those of commercial a-Se detectors. CdTe
      has cubic Zinc Blende structure and maintains p-type conduction after growth in
      general. For low voltage operation, we succeeded in Cl doping at all stage of
      CdTe film deposition, and as a result, hole concentration of p-type CdTe was
      reduced to ~1012 cm-3 from ~1015 cm-3, and such concentration reduction could
      enable our Schottky diode with Ti electrode to operate at a reverse bias of less
      than 40 V. Our CdTe Schottky diode/CMOS pixel array as a direct conversion type
      imager demonstrates much higher resolution X-ray imaging in 7 * 9 cm2 large scale
      than that of CsI/CMOS array, an indirect conversion imager. To our limited
      knowledge, our results on polycrystalline CdTe Schottky diode/CMOS array would be
      very novel as a first demonstration of active pixel sensor system equipped with
      directly deposited large scale X-ray detector.

PMID- 30287873
TI  - Low dose dimethyl sulfoxide driven gross molecular changes have the potential to
      interfere with various cellular processes.
AB  - Dimethyl sulfoxide (DMSO) is a small molecule with polar, aprotic and amphiphilic
      properties. It serves as a solvent for many polar and nonpolar molecules and
      continues to be one of the most used solvents (vehicle) in medical applications
      and scientific research. To better understand the cellular effects of DMSO within
      the concentration range commonly used as a vehicle (0.1-1.5%, v/v) for cellular
      treatments, we applied Attenuated Total Reflectance (ATR) Fourier Transform
      Infrared (FT-IR) spectroscopy to DMSO treated and untreated epithelial colon
      cancer cells. Both unsupervised (Principal Component Analysis-PCA) and supervised
      (Linear Discriminant Analysis-LDA) pattern recognition/modelling algorithms
      applied to the IR data revealed total segregation and prominent differences
      between DMSO treated and untreated cells at whole, lipid and nucleic acid
      regions. Several of these data were supported by other independent techniques.
      Further IR data analyses of macromolecular profile indicated comprehensive
      alterations especially in proteins and nucleic acids. Protein secondary structure
      analysis showed predominance of beta-sheet over alpha-helix in DMSO treated
      cells. We also observed for the first time, a reduction in nucleic acid level
      upon DMSO treatment accompanied by the formation of Z-DNA. Molecular docking and
      binding free energy studies indicated a stabilization of Z-DNA in the presence of
      DMSO. This alternate DNA form may be related with the specific actions of DMSO on
      gene expression, differentiation, and epigenetic alterations. Using analytical
      tools combined with molecular and cellular biology techniques, our data indicate
      that even at very low concentrations, DMSO induces a number of changes in all
      macromolecules, which may affect experimental outcomes where DMSO is used as a
      solvent.

PMID- 30287877
TI  - Refocusing IBD Patient Management: Personalized, Proactive, and Patient-Centered
      Care.
AB  - Medications are available that can be highly effective for the treatment of
      inflammatory bowel disease (IBD). However, there are multiple barriers in place
      to offer these treatments to the right patients at the right time. In addition to
      obstacles created by payers, there are concerns over medication side effects by
      patients and providers, and the logistic challenges of navigating the maze of
      initiating someone on biological therapy. As a gastroenterology community, we
      need to push the field forward for the sake of our patients. Current and future
      drug development for IBD is exciting, but we need to optimize what we have now to
      the best of our ability. When used appropriately and early enough in the disease
      course, our current medications can heal the bowel and prevent complications from
      developing. While recognizing that all patients do not need early intensive
      therapy, we need to identify the appropriate patients for more aggressive
      treatments. This article will describe how we can improve patient management now
      by shifting our focus to using a personalized, proactive, and patient-centered
      approach in our delivery of IBD care.

PMID- 30287875
TI  - Prolonged bacterial lag time results in small colony variants that represent a
      sub-population of persisters.
AB  - Persisters are a subpopulation of bacteria that are not killed by antibiotics
      even though they lack genetic resistance. Here we provide evidence that
      persisters can manifest as small colony variants (SCVs) in clinical infections.
      We analyze growth kinetics of Staphylococcus aureus sampled from in vivo
      conditions and in vitro stress conditions that mimic growth in host compartments.
      We report that SCVs arise as a result of a long lag time, and that this phenotype
      emerges de novo during the growth phase in various stress conditions including
      abscesses and acidic media. We further observe that long lag time correlates with
      antibiotic usage. These observations suggest that treatment strategies should be
      carefully tailored to address bacterial persisters in clinics.

PMID- 30287876
TI  - Mutation pattern analysis reveals polygenic mini-drivers associated with relapse
      after surgery in lung adenocarcinoma.
AB  - The genomic lesions found in malignant tumours exhibit a striking degree of
      heterogeneity. Many tumours lack a known driver mutation, and their genetic basis
      is unclear. By mapping the somatic mutations identified in primary lung
      adenocarcinomas onto an independent coexpression network derived from normal
      tissue, we identify a critical gene network enriched for metastasis-associated
      genes. While individual genes within this module were rarely mutated, a
      significant accumulation of mutations within this geneset was predictive of
      relapse in lung cancer patients that have undergone surgery. Since it is the
      density of mutations within this module that is informative, rather than the
      status of any individual gene, these data are in keeping with a 'mini-driver'
      model of tumorigenesis in which multiple mutations, each with a weak effect,
      combine to form a polygenic driver with sufficient power to significantly alter
      cell behaviour and ultimately patient outcome. These polygenic mini-drivers
      therefore provide a means by which heterogeneous mutation patterns can generate
      the consistent hallmark changes in phenotype observed across tumours.

PMID- 30287879
TI  - Upregulation of Nav1.6 expression in the rostral ventrolateral medulla of stress
      induced hypertensive rats.
AB  - The rostral ventrolateral medulla (RVLM) plays a key role in mediating the
      development of stress-induced hypertension (SIH) by excitation and/or inhibition
      of sympathetic preganglionic neurons. The voltage-gated sodium channel Nav1.6 has
      been found to contribute to neuronal hyperexcitability. To examine the expression
      of Nav1.6 in the RVLM during SIH, a rat model was established by administering
      electric foot-shocks and noises. We found that Nav1.6 protein expression in the
      RVLM of SIH rats was higher than that of control rats, peaking at the tenth day
      of stress. Furthermore, we observed changes in blood pressure correlating with
      days of stress, with systolic blood pressure (SBP) found to reach a similarly
      timed peak at the tenth day of stress. Percentages of cells exhibiting
      colocalization of Nav1.6 with NeuN, a molecular marker of neurons, indicated a
      strong correlation between upregulation of Nav1.6 expression in NeuN-positive
      cells and SBP. The level of RSNA was significantly increased after 10 days of
      stress induction than control group. Compared with the SIHR, knockdown of Nav1.6
      in RVLM of the SIHR decreased the level of SBP, heart rate (HR) and renal
      sympathetic nerve activity (RSNA). These results suggest that upregulated Nav1.6
      expression within neurons in the RVLM of SIH rats may contribute to
      overactivation of the sympathetic system in response to SIH development.

PMID- 30287878
TI  - Influence of water quality on diversity and composition of fungal communities in
      a tropical river.
AB  - Freshwater fungi are key decomposers of organic material and play important roles
      in nutrient cycling, bio-remediation and ecosystem functioning. Although aquatic
      fungal communities respond to pollution, few studies have quantitatively assessed
      the effect of freshwater contamination on fungal diversity and composition; and
      knowledge is scarcer for tropical systems. Here we help fill this knowledge gap
      by studying a heavily-contaminated South American river spanning a biodiversity
      hotspot. We collected 30 water samples scattered across a quality gradient over
      two seasons and analyzed them using Terminal Restriction Fragment Length
      Polymorphisms (T-RFLP) coupled with 454 Pyrosequencing. Using T-RFLP we
      identified 451 and 442 Operational Taxonomy Units (OTUs) in the dry and rainy
      seasons respectively, whereas Pyrosequencing revealed 48,553 OTUs from which 11%
      were shared between seasons. Although 68% of all identified OTUs and 51% of all
      identified phyla remained unidentified, dominant fungal phyla included the
      Ascomycota, Basidiomycota, Chytridiomycota, Glomeromycota, Zygomycota and
      Neocallimastigomycota, while Calcarisporiella, Didymosphaeria, Mycosphaerella
      (Ascomycota) and Rhodotorula (Basidiomycota) were the most abundant genera.
      Fungal diversity was affected by pH and dissolved iron, while community
      composition was influenced by dissolved oxygen, pH, nitrate, biological oxygen
      demand, total aluminum, total organic carbon, total iron and seasonality. The
      presence of potentially pathogenic species was associated with high pH.
      Furthermore, geographic distance was positively associated with community
      dissimilarity, suggesting that local conditions allowed divergence among fungal
      communities. Overall, our findings raise potential concerns for human health and
      the functioning of tropical river ecosystems and they call for improved water
      sanitation systems.

PMID- 30287881
TI  - Stimulated Brillouin Scattering in an AlGaN Photonics Platform Operating in the
      Visible Spectral Range.
AB  - We present Stimulated Brillouin Scattering (SBS) process in AlGaN integrated
      photonic waveguides. The wide bandgap of this III-Nitride material platform
      allows operating at visible wavelengths enabling large Stokes shifts. For this
      study, we employ a multiphysics approach that includes electric-photoelastic,
      magnetic-photoelastic, material interface displacement effects, and for optimal
      waveguide dimensions to find the Brillouin-active acoustic modes involved in the
      SBS process. The SBS power gain and the Stokes frequency shift are investigated
      for both backward and forward scattering processes, and it is shown that stokes
      shift larger than 50 GHz with high gain are achievable. Moreover, a parametric
      analysis is presented in order to demonstrate the possibility of realizing
      Brillouin lasers operating at blue wavelengths.

PMID- 30287880
TI  - Mutation of TP53, translocation analysis and immunohistochemical expression of
      MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP.
AB  - Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with diverse
      outcomes. Concurrent translocation of MYC and BCL-2 and/or BCL-6, and concurrent
      immunohistochemical (IHC) high expression of MYC and BCL-2, have been linked to
      unfavorable treatment responses. TP53-mutated DLBCL has also been linked to worse
      outcome. Our aim was to evaluate the aforementioned issues in a cohort of 155
      patients uniformly treated with R-CHOP-like therapies. We performed direct
      sequencing of TP53 exons 5, 6, 7 and 8 as well as fluorescence in-situ
      hybridization (FISH) of MYC, BCL-2 and BCL-6, and IHC of MYC, BCL-2 and BCL-6. In
      multivariate analysis, TP53 mutations in L3 and loop-sheet helix (LSH) associated
      with a risk ratio (RR) of disease-specific survival (DSS) of 8.779 (p = 0.022)
      and a RR of disease-free survival (DFS) of 10.498 (p = 0.011). In IHC analysis
      BCL-2 overexpression was associated with inferior DFS (p = 0.002) and DSS (p =
      0.002). DLBCL with BCL-2 and MYC overexpression conferred inferior survival in
      all patients (DSS, p = 0.038 and DFS, p = 0.011) and in patients with non-GC
      phenotype (DSS (p = 0.013) and DFS (p = 0.010). Our results imply that in DLBCL,
      the location of TP53 mutations and IHC analysis of BCL-2 and MYC might have a
      role in the assessment of prognosis.

PMID- 30287883
TI  - Ovarian hormones, genes, and the brain: the case of estradiol and the brain
      derived neurotrophic factor (BDNF) gene.

PMID- 30287882
TI  - Two Engineered OBPs with opposite temperature-dependent affinities towards 1
      aminoanthracene.
AB  - Engineered odorant-binding proteins (OBPs) display tunable binding affinities
      triggered by temperature alterations. We designed and produced two engineered
      proteins based on OBP-I sequence: truncated OBP (tOBP) and OBP::GQ20::SP-DS3. The
      binding affinity of 1-aminoanthracene (1-AMA) to these proteins revealed that
      tOBP presents higher affinity at 25  degrees C (kd = 0.45 MUM) than at 37 
      degrees C (kd = 1.72 MUM). OBP::GQ20::SP-DS3 showed an opposite behavior,
      revealing higher affinity at 37  degrees C (kd = 0.58 MUM) than at 25  degrees C
      (kd = 1.17 MUM). We set-up a system containing both proteins to evaluate their
      temperature-dependent binding. Our data proved the 1-AMA differential and
      reversible affinity towards OBPs, triggered by temperature changes. The
      variations of the binding pocket size with temperature, confirmed by molecular
      modelling studies, were determinant for the differential binding of the
      engineered OBPs. Herein we described for the first time a competitive temperature
      dependent mechanism for this class of proteins.

PMID- 30287884
TI  - Clock transition by continuous dynamical decoupling of a three-level system.
AB  - We present a novel continuous dynamical decoupling scheme for the construction of
      a robust qubit in a three-level system. By means of a clock transition
      adjustment, we first show how robustness to environmental noise is achieved,
      while eliminating drive-noise, to first-order. We demonstrate this scheme with
      the spin sub-levels of the NV-centre's electronic ground state. By applying drive
      fields with moderate Rabi frequencies, the drive noise is eliminated and an
      improvement of 2 orders of magnitude in the coherence time is obtained compared
      to the pure dephasing time. We then show how the clock transition adjustment can
      be tuned to eliminate also the second-order effect of the environmental noise
      with moderate drive fields. A further detailed theoretical investigation suggests
      an additional improvement of more than 1 order of magnitude in the coherence time
      which is supported by simulations. Hence, our scheme predicts that the coherence
      time may be prolonged towards the lifetime-limit using a relatively simple
      experimental setup.

PMID- 30287885
TI  - Genome analyses of uncultured TG2/ZB3 bacteria in 'Margulisbacteria' specifically
      attached to ectosymbiotic spirochetes of protists in the termite gut.
AB  - We investigated the phylogenetic diversity, localisation and metabolism of an
      uncultured bacterial clade, Termite Group 2 (TG2), or ZB3, in the termite gut,
      which belongs to the candidate phylum 'Margulisbacteria'. We performed 16S rRNA
      amplicon sequencing analysis and detected TG2/ZB3 sequences in 40 out of 72
      termite and cockroach species, which exclusively constituted a monophyletic
      cluster in the TG2/ZB3 clade. Fluorescence in situ hybridisation analysis in
      lower termites revealed that these bacteria are specifically attached to
      ectosymbiotic spirochetes of oxymonad gut protists. Draft genomes of four TG2/ZB3
      phylotypes from a small number of bacterial cells were reconstructed, and
      functional genome analysis suggested that these bacteria hydrolyse and ferment
      cellulose/cellobiose to H2, CO2, acetate and ethanol. We also assembled a draft
      genome for a partner Treponema spirochete and found that it encoded genes for
      reductive acetogenesis from H2 and CO2. We hypothesise that the TG2/ZB3 bacteria
      we report here are commensal or mutualistic symbionts of the spirochetes,
      exploiting the spirochetes as H2 sinks. For these bacteria, we propose a novel
      genus, 'Candidatus Termititenax', which represents a hitherto uncharacterised
      class-level clade in 'Margulisbacteria'. Our findings add another layer, i.e.,
      cellular association between bacteria, to the multi-layered symbiotic system in
      the termite gut.

PMID- 30287886
TI  - 'NetShift': a methodology for understanding 'driver microbes' from healthy and
      disease microbiome datasets.
AB  - The combined effect of mutual association within the co-inhabiting microbes in
      human body is known to play a major role in determining health status of
      individuals. The differential taxonomic abundance between healthy and disease are
      often used to identify microbial markers. However, in order to make a microbial
      community based inference, it is important not only to consider microbial
      abundances, but also to quantify the changes observed among inter microbial
      associations. In the present study, we introduce a method called 'NetShift' to
      quantify rewiring and community changes in microbial association networks between
      healthy and disease. Additionally, we devise a score to identify important
      microbial taxa which serve as 'drivers' from the healthy to disease. We
      demonstrate the validity of our score on a number of scenarios and apply our
      methodology on two real world metagenomic datasets. The 'NetShift' methodology is
      also implemented as a web-based application available at
      https://web.rniapps.net/netshift.

PMID- 30287888
TI  - Statistical testing for baseline differences between randomised groups is not
      meaningful.

PMID- 30287887
TI  - Device-independent quantum random-number generation.
AB  - Randomness is important for many information processing applications, including
      numerical modelling and cryptography1,2. Device-independent quantum random-number
      generation (DIQRNG)3,4 based on the loophole-free violation of a Bell inequality
      produces genuine, unpredictable randomness without requiring any assumptions
      about the inner workings of the devices, and is therefore an ultimate goal in the
      field of quantum information science5-7. Previously reported experimental
      demonstrations of DIQRNG8,9 were not provably secure against the most general
      adversaries or did not close the 'locality' loophole of the Bell test. Here we
      present DIQRNG that is secure against quantum and classical adversaries10-12. We
      use state-of-the-art quantum optical technology to create, modulate and detect
      entangled photon pairs, achieving an efficiency of more than 78 per cent from
      creation to detection at a distance of about 200 metres that greatly exceeds the
      threshold for closing the 'detection' loophole of the Bell test. By independently
      and randomly choosing the base settings for measuring the entangled photon pairs
      and by ensuring space-like separation between the measurement events, we also
      satisfy the no-signalling condition and close the 'locality' loophole of the Bell
      test, thus enabling the realization of the loophole-free violation of a Bell
      inequality. This, along with a high-voltage, high-repetition-rate Pockels cell
      modulation set-up, allows us to accumulate sufficient data in the experimental
      time to extract genuine quantum randomness that is secure against the most
      general adversaries. By applying a large (137.90 gigabits * 62.469 megabits)
      Toeplitz-matrix hashing technique, we obtain 6.2469 * 107 quantum-certified
      random bits in 96 hours with a total failure probability (of producing a random
      number that is not guaranteed to be perfectly secure) of less than 10-5. Our
      demonstration is a crucial step towards transforming DIQRNG from a concept to a
      key aspect of practical applications that require high levels of security and
      thus genuine randomness7. Our work may also help to improve our understanding of
      the origin of randomness from a fundamental perspective.

PMID- 30287890
TI  - Exploration of potential biochemical markers for persistence of patent ductus
      arteriosus in preterm infants at 22-27 weeks' gestation.
AB  - BACKGROUND: Early identification of infants at risk for complications from patent
      ductus arteriosus (PDA) may improve treatment outcomes. The aim of this study was
      to identify biochemical markers associated with persistence of PDA, and with
      failure of pharmacological treatment for PDA, in extremely preterm infants.
      METHODS: Infants born at 22-27 weeks' gestation were included in this prospective
      study. Blood samples were collected on the second day of life. Fourteen
      biochemical markers associated with factors that may affect PDA closure were
      analyzed and related to persistent PDA and to the response of pharmacological
      treatment with ibuprofen. RESULTS: High levels of B-type natriuretic peptide,
      interleukin-6, -8, -10, and -12, growth differentiation factor 15 and monocyte
      chemotactic protein 1 were associated with persistent PDA, as were low levels of
      platelet-derived growth factor. High levels of erythropoietin were associated
      with both persistent PDA and failure to close PDA within 24 h of the last dose of
      ibuprofen. CONCLUSIONS: High levels of inflammatory markers were associated with
      the persistence of PDA. High levels of erythropoietin were associated with both
      the persistence of PDA and failure to respond to pharmacological treatment.

PMID- 30287891
TI  - Gene ontology enrichment analysis of congenital diaphragmatic hernia-associated
      genes.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) is a commonly occurring major
      congenital anomaly with a profound impact on neonatal mortality. The etiology of
      CDH is poorly understood and is complicated by multiple clinical presentations,
      reflecting the location and type of diaphragm defect. With the increased power of
      genetic screening, more genes are being associated with CDH, creating a knowledge
      gap between CDH-associated genes and their contribution to diaphragm
      embryogenesis. METHODS: Our goal was to investigate CDH-associated genes and
      identify common pathways that may lead to abnormal diaphragm development. A
      comprehensive list of CDH-associated genes was identified from the literature and
      categorized according to multiple factors, including type of CDH. We undertook a
      large-scale gene function analysis using gene ontology to identify significantly
      enriched biological pathways and molecular functions associated with our gene
      set. RESULTS: We identified 218 CDH-associated genes. Our gene ontology analysis
      showed that genes representing distinct biological pathways are significantly
      enriched in relation to different clinical presentations of CDH. This includes
      retinoic acid signaling in Bochdalek CDH, myogenesis in diaphragm eventration,
      and angiogenesis in central tendon defects. CONCLUSIONS: We have identified
      unique genotype-phenotype relationships highlighting the major genetic drivers of
      the different types of CDH.

PMID- 30287889
TI  - Molecular characterization, antimicrobial resistance and clinico-bioinformatics
      approaches to address the problem of extended-spectrum beta-lactamase-producing
      Escherichia coli in western Saudi Arabia.
AB  - The goal of this study was to genotypically characterize extended-spectrum beta
      lactamase-producing Escherichia coli isolates from the western region of Saudi
      Arabia and to identify active antibiotics against these isolates using phenotypic
      and molecular modeling. In total, 211 ESBL-producing E. coli isolates recovered
      from heterogeneous clinical specimens were identified by MALDI-TOF. Thirty-two
      sequence types (STs) were identified from a multilocus sequence typing (MLST)
      analysis of ESBL-producing E. coli, including a novel ST (ST8162). The most
      common ST in the Saudi and expatriate population was ST131, followed by ST38. All
      the isolates were multidrug resistant (MDR), and >95% of the isolates were
      resistant to third-generation (ceftriaxone and ceftazidime) and fourth-generation
      (cefepime) cephalosporins. The ESBL-positive E. coli isolates primarily harbored
      the blaCTX-M and blaTEM genes. No resistance was observed against the carbapenem
      antibiotic group. All the ESBL-producing E. coli isolates were observed to be
      susceptible to a ceftazidime/avibactam combination. Molecular interaction
      analyses of the docked complexes revealed the amino acid residues crucial for the
      binding of antibiotics and inhibitors to the modeled CTX-M-15 enzyme.
      Importantly, avibactam displayed the most robust interaction with CTX-M-15 among
      the tested inhibitors in the docked state (?G = -6.6 kcal/mol). The binding free
      energy values for clavulanate, tazobactam and sulbactam were determined to be 
      5.7, -5.9 and -5.2 kcal/mol, respectively. Overall, the study concludes that
      'ceftazidime along with avibactam' should be carefully used as a treatment option
      against only carbapenem-resistant MDR ESBL-producing E. coli in this region.

PMID- 30287892
TI  - Body mass index classification misses to identify children with an elevated waist
      to-height ratio at 5 years of age.
AB  - BACKGROUND: Abdominal adiposity is an important risk factor in the metabolic
      syndrome. Since BMI does not reveal fat distribution, waist-to-height ratio
      (WHtR) has been suggested as a better measure of abdominal adiposity in children,
      but only a few studies cover the preschool population. The aim of the present
      study was to examine BMI and WHtR growth patterns and their association regarding
      their ability to identify children with an elevated WHtR at 5 years of age.
      METHODS: A population-based longitudinal birth cohort study of 1540 children,
      followed from 0 to 5 years with nine measurement points. The children were
      classified as having WHtR standard deviation scores (WHtRSDS) <1 or >=1 at 5
      years. Student's t-tests and Chi-squared tests were used in the analyses.
      RESULTS: Association between BMISDS and WHtRSDS at 5 years showed that 55% of
      children with WHtRSDS >=1 at 5 years had normal BMISDS (p < 0.001). Children with
      WHtRSDS >=1 at 5 years had from an early age significantly higher mean BMISDS and
      WHtRSDS than children with values <1. CONCLUSIONS: BMI classification misses
      every second child with WHtRSDS >=1 at 5 years, suggesting that WHtR adds value
      in identifying children with abdominal adiposity who may need further
      investigation regarding cardiometabolic risk factors.

PMID- 30287893
TI  - Capturing the statewide incidence of neonatal abstinence syndrome in real time:
      the West Virginia experience.
AB  - BACKGROUND: Neonatal abstinence syndrome (NAS) is one of the consequences at
      birth affecting the newborn after discontinuation of prenatal drug exposure to
      mainly opioids. The objective of this study was to determine the extent of the
      problem in the state of West Virginia (WV) using a real-time statewide
      surveillance system. METHODS: Project WATCH is a surveillance tool that since
      1998 collects data on all infants born in the state of WV. NAS surveillance item
      was added to the tool in October 2016. This study examined all births (N =
      23,667) in WV from October to December 2017. The data from six WV birthing
      facilities were audited for 1 month to evaluate how well this tool was capturing
      NAS data using kappa-statistics. RESULTS: The 2017 annual incidence rate of NAS
      was 51.3 per 1000 live births per year for all births and 50.6 per 1000 live
      births per year for WV residents only. The kappa-coefficient between the hospital
      medical records and Project WATCH data was 0.74 (95% confidence interval: 0.66
      0.82) for NAS. CONCLUSION: The study provides justification to develop effective
      systems of care for the mother-infant dyad affected by substance use, especially
      targeting pregnant women in rural communities.

PMID- 30287894
TI  - Serum L-carnitine and vitamin D levels may be low among oral sildenafil citrate
      non-responders.
AB  - This cross-sectional comparative study aimed to compare serum L-carnitine and
      25(OH)D levels between men with ED non-responding for oral sildenafil citrate and
      healthy volunteers. Overall, 192 men, recruited from two University Hospitals,
      were allocated into two equal groups of matched age; healthy potent men and men
      with ED non-responders for oral sildenafil citrate. Oral sildenafil citrate non
      responders self-reported inadequate erectile responses after four attempts using
      100 mg with the manufacturer's guidelines relative to meals, associated
      medications, and sexual stimulation/arousal. Exclusion criteria were: diabetes,
      cardiovascular disorders, beta blockers treatment, morbid obesity, thyroid
      disorders, post-radical prostatectomy, and hepatic/renal failure. All
      participants were subjected to; history taking, clinical examination, validated
      IIEF-5 questionnaire, estimation of serum L-carnitine by calorimetric method and
      serum 25(OH)D by ELISA method. Compared with potent controls, ED men non
      responders for oral sildenafil citrate showed significant decreases in the mean
      serum L-carnitine level (16.8 +/- 3.6 uM/L versus 66.3 +/- 11.9 uM/L, P = 0.001),
      the mean serum 25(OH)D level (21.2 +/- 7.1 ng/ml versus 54.6 +/- 7.9 ng/mL, P =
      0.001) and IIEF-5 score (7.8 +/- 2.6 versus 23.9 +/- 1.3). Serum L-carnitine
      showed significant positive correlation with IIEF-5 scores (r = 0.873, P = 001),
      serum 25(OH)D (r = 0.796, P = 0.001) and significant negative correlation with
      the age (r = -0.515, P = 0.001). Serum 25(OH)D showed significant positive
      correlation with IIEF-5 scores (r = 0.855, P = 0.001) and significant negative
      correlation with the age (r = -0.223, P = 0.005). It is concluded that normal
      homeostasis of serum L-carnitine and 25(OH)D play a role in male sexual health
      being significantly decreased in ED non-responding for oral sildenafil citrate.

PMID- 30287895
TI  - Author Correction: A Donor Quality Index for liver transplantation: development,
      internal and external validation.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30287896
TI  - A multiplexed view of immune infiltration.

PMID- 30287898
TI  - Newborn dried blood spot samples in Denmark: the hidden figures of secondary use
      and research participation.
AB  - Each year millions of newborns are part of a newborn disease-screening program in
      which, after initial screening, the newborn dried blood spot (NDBS) samples can
      be stored and used as a population-based research resource. However, very little
      knowledge exists about how these samples are used for secondary purposes. Our
      objective is to estimate and describe the usage of a NDBS-based national
      population biobank for secondary research purposes. We therefore conducted a
      scoping study with a literature search for all published articles using samples
      from the Danish Newborn Screening Biobank. Our main inclusion criteria were that
      the articles had to have actively used and analyzed one or more of the Danish
      NDBS samples for a purpose beyond the primary screening. Our search led to a
      final 104 articles, which were coded for three main purposes: (1) how many
      samples were used in each article, (2) the field of their research, and (3)
      information on consent and ethics approval as research. From our analysis, we
      present two main findings: an estimated use of up to 37.5% of all samples in the
      newborn screening biobank have been part of published research, and a shift in
      the research areas from methodological and metabolic studies to studies
      concerning mental illness. This paper provides new insights into the use of a
      national biobank, and we hope that the results will contribute to the discussions
      on the use of biological samples for research purposes, and also inspire a
      greater transparency in the future use of NDBS samples.

PMID- 30287899
TI  - Presymptomatic genetic testing for hereditary cancer in young adults: a survey of
      young adults and parents.
AB  - Presymptomatic testing for hereditary cancer syndromes should involve a
      considered choice. This may be particularly challenging when testing is
      undertaken in early adulthood. With the aim of exploring the psychosocial
      implications of presymptomatic testing for hereditary cancer in young adults and
      their parents, a cross-sectional survey was designed. Two questionnaires were
      developed (one for young adults who had considered presymptomatic testing, one
      for parents). Questionnaires were completed by 152 (65.2%) young adults and 42
      (73.7%) parents. Data were analysed using descriptive statistics, inferential
      testing, and exploratory factor analysis and linear regression analysis. Young
      adults were told about their potential genetic risk at a mean age of 20 years; in
      most cases, information was given by a parent, often in an unplanned
      conversation. Although testing requests were usually made by young adults, the
      majority of parents felt they had control over the young adult's decision and all
      felt their children should be tested. Results suggest that some young adults did
      not understand the implications of the genetic test but complied with parental
      pressure. Counselling approaches for presymptomatic testing may require
      modification both for young adults and their parents. Those offering testing need
      to be aware of the complex pressures that young adults can experience, which can
      influence their autonomous choices. It is therefore important to emphasise to
      both parents and young adults that, although testing can bring benefits in terms
      of surveillance and prevention, young adults have a choice.

PMID- 30287897
TI  - A multisubstrate reductase from Plantago major: structure-function in the short
      chain reductase superfamily.
AB  - The short chain dehydrogenase/reductase superfamily (SDR) is a large family of
      NAD(P)H-dependent enzymes found in all kingdoms of life. SDRs are particularly
      well-represented in plants, playing diverse roles in both primary and secondary
      metabolism. In addition, some plant SDRs are also able to catalyse a reductive
      cyclisation reaction critical for the biosynthesis of the iridoid backbone that
      contains a fused 5 and 6-membered ring scaffold. Mining the EST database of
      Plantago major, a medicinal plant that makes iridoids, we identified a putative
      5beta-progesterone reductase gene, PmMOR (P. major multisubstrate oxido
      reductase), that is 60% identical to the iridoid synthase gene from Catharanthus
      roseus. The PmMOR protein was recombinantly expressed and its enzymatic activity
      assayed against three putative substrates, 8-oxogeranial, citral and
      progesterone. The enzyme demonstrated promiscuous enzymatic activity and was able
      to not only reduce progesterone and citral, but also to catalyse the reductive
      cyclisation of 8-oxogeranial. The crystal structures of PmMOR wild type and PmMOR
      mutants in complex with NADP+ or NAD+ and either 8-oxogeranial, citral or
      progesterone help to reveal the substrate specificity determinants and catalytic
      machinery of the protein. Site-directed mutagenesis studies were performed and
      provide a foundation for understanding the promiscuous activity of the enzyme.

PMID- 30287901
TI  - Autoreactive T cells in narcolepsy.

PMID- 30287900
TI  - FGF-7 Dictates Osteocyte Cell Processes Through Beta-Catenin Transduction.
AB  - It is well recognized that osteocytes communicate with each other via gap
      junctions and that connxin43 (Cx43) shows its great potential in gap junction for
      the contribution enabling transmission of small molecules and operating in an
      autocrine/a paracrine manner. Fibroblast growth factors (FGFs) play significant
      roles in new bone formation and adult bone remodeling, and FGF signaling is
      regulated by the precise spatiotemporal approaches. However, the influence of
      FGF7 on osteocyte cell processes is not well elucidated. In this study, we aimed
      to examine the impact of FGF7 on osteocyte cell processes by characterizing the
      expression of Cx43 and to reveal the underlying mechanism regulating this cell
      process. We first found that the mRNA level of FGF7 was higher relative to other
      FGF family members both in osteocytes cell line (MLO-Y4) and bone tissue. We then
      demonstrated that FGF7 could increase the expression of Cx43 in osteocytes and
      promote the cell processes in the form of gap junctions between osteocytes. This
      modulation was due to the FGF7-induced cytoplasmic accumulation and resultant
      nuclear translocation of beta-catenin. Our results could help us to further
      understand the importance of FGF7 on bone cell behavior and bone physiology and
      even pathology.

PMID- 30287902
TI  - Repurposing of promoters and enhancers during mammalian evolution.
AB  - Promoters and enhancers-key controllers of gene expression-have long been
      distinguished from each other based on their function. However, recent work
      suggested that common architectural and functional features might have
      facilitated the conversion of one type of element into the other during
      evolution. Here, based on cross-mammalian analyses of epigenome and transcriptome
      data, we provide support for this hypothesis by detecting 445 regulatory elements
      with signatures of activity turnover (termed P/E elements). Most events represent
      transformations of putative ancestral enhancers into promoters, leading to the
      emergence of species-specific transcribed loci or 5' exons. Distinct GC sequence
      compositions and stabilizing 5' splicing (U1) regulatory motif patterns may have
      predisposed P/E elements to regulatory repurposing, and changes in the U1 and
      polyadenylation signal densities and distributions likely drove the evolutionary
      activity switches. Our work suggests that regulatory repurposing facilitated
      regulatory innovation and the origination of new genes and exons during
      evolution.

PMID- 30287905
TI  - Who improves from coma, how do they improve, and then what?

PMID- 30287903
TI  - Determination of the Main Phase Transition Temperature of Phospholipids by
      Nanoplasmonic Sensing.
AB  - Our study demonstrates that nanoplasmonic sensing (NPS) can be utilized for the
      determination of the phase transition temperature (Tm) of phospholipids. During
      the phase transition, the lipid bilayer undergoes a conformational change.
      Therefore, it is presumed that the Tm of phospholipids can be determined by
      detecting conformational changes in liposomes. The studied lipids included 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC), and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC).
      Liposomes in gel phase are immobilized onto silicon dioxide sensors and the
      sensor cell temperature is increased until passing the Tm of the lipid. The
      results show that, when the system temperature approaches the Tm, a drop of the
      NPS signal is observed. The breakpoints in the temperatures are 22.5  degrees C,
      41.0  degrees C, and 55.5  degrees C for DMPC, DPPC, and DSPC, respectively.
      These values are very close to the theoretical Tm values, i.e., 24  degrees C,
      41.4  degrees C, and 55  degrees C for DMPC, DPPC, and DSPC, respectively. Our
      studies prove that the NPS methodology is a simple and valuable tool for the
      determination of the Tm of phospholipids.

PMID- 30287904
TI  - Pattern to Knowledge: Deep Knowledge-Directed Machine Learning for Residue
      Residue Interaction Prediction.
AB  - Residue-residue close contact (R2R-C) data procured from three-dimensional
      protein-protein interaction (PPI) experiments is currently used for predicting
      residue-residue interaction (R2R-I) in PPI. However, due to complex
      physiochemical environments, R2R-I incidences, facilitated by multiple factors,
      are usually entangled in the source environment and masked in the acquired data.
      Here we present a novel method, P2K (Pattern to Knowledge), to disentangle R2R-I
      patterns and render much succinct discriminative information expressed in
      different specific R2R-I statistical/functional spaces. Since such knowledge is
      not visible in the data acquired, we refer to it as deep knowledge. Leveraging
      the deep knowledge discovered to construct machine learning models for sequence
      based R2R-I prediction, without trial-and-error combination of the features over
      external knowledge of sequences, our R2R-I predictor was validated for its
      effectiveness under stringent leave-one-complex-out-alone cross-validation in a
      benchmark dataset, and was surprisingly demonstrated to perform better than an
      existing sequence-based R2R-I predictor by 28% (p: 1.9E-08). P2K is accessible
      via our web server on https://p2k.uwaterloo.ca .

PMID- 30287906
TI  - A cross-species approach to disorders affecting brain and behaviour.
AB  - Structural and functional elements of biological systems are highly conserved
      across vertebrates. Many neurological and psychiatric conditions affect both
      humans and animals. A cross-species approach to the study of brain and behaviour
      can advance our understanding of human disorders via the identification of
      unrecognized natural models of spontaneous disorders, thus revealing novel
      factors that increase vulnerability or resilience, and via the assessment of
      potential therapies. Moreover, diagnostic and therapeutic advances in human
      neurology and psychiatry can often be adapted for veterinary patients. However,
      clinical and research collaborations between physicians and veterinarians remain
      limited, leaving this wealth of comparative information largely untapped. Here,
      we review pain, cognitive decline syndromes, epilepsy, anxiety and compulsions,
      autoimmune and infectious encephalitides and mismatch disorders across a range of
      animal species, looking for novel insights with translational potential. This
      comparative perspective can help generate novel hypotheses, expand and improve
      clinical trials and identify natural animal models of disease resistance and
      vulnerability.

PMID- 30287907
TI  - Photoacclimation strategies in northeastern Atlantic seagrasses: Integrating
      responses across plant organizational levels.
AB  - Seagrasses live in highly variable light environments and adjust to these
      variations by expressing acclimatory responses at different plant organizational
      levels (meadow, shoot, leaf and chloroplast level). Yet, comparative studies, to
      identify species' strategies, and integration of the relative importance of
      photoacclimatory adjustments at different levels are still missing. The variation
      in photoacclimatory responses at the chloroplast and leaf level were studied
      along individual leaves of Cymodocea nodosa, Zostera marina and Z. noltei,
      including measurements of variable chlorophyll fluorescence, photosynthesis,
      photoprotective capacities, non-photochemical quenching and D1-protein repair,
      and assessments of variation in leaf anatomy and chloroplast distribution. Our
      results show that the slower-growing C. nodosa expressed rather limited
      physiological and biochemical adjustments in response to light availability,
      while both species of faster-growing Zostera showed high variability along the
      leaves. In contrast, the inverse pattern was found for leaf anatomical
      adjustments in response to light availability, which were more pronounced in C.
      nodosa. This integrative plant organizational level approach shows that
      seagrasses differ in their photoacclimatory strategies and that these are linked
      to the species' life history strategies, information that will be critical for
      predicting the responses of seagrasses to disturbances and to accordingly develop
      adequate management strategies.

PMID- 30287908
TI  - Metabarcoding of marine environmental DNA based on mitochondrial and nuclear
      genes.
AB  - We establish the new approach of environmental DNA (eDNA) analyses for the North
      Sea. Our study uses a multigene approach, including the mitochondrial cytochrome
      c-oxidase subunit I (COI) gene for analyzing species composition and the nuclear
      hypervariable region V8 of 18S rDNA for analyzing supraspecific biodiversity. A
      new minibarcode primer (124 bp) was created on the basis of a metazoan COI
      barcode library with 506 species and tested in silico, in vitro, and in situ. We
      applied high throughput sequencing to filtrates of 23 near-bottom water samples
      taken at three seasons from 14 stations. The set of COI primers allowed
      amplification of mitochondrial minibarcodes for diverse metazoan phyla and the
      differentiation at the species level for more than 99% of the specimens in the
      dataset. Our results revealed that the number of sequences is not consistent with
      proportions in the given DNA mixture. Altogether, environmental sequences could
      be assigned to 114 species and to 12 metazoan phyla. A spatial distribution of
      taxa recovered by eDNA was congruent with known distributions. Finally, the
      successful detection of species and biodiversity depends on a comprehensive
      sequence reference database. Our study offers a powerful tool for future
      biodiversity research, including the detection of nonnative species.

PMID- 30287909
TI  - Polymorphisms at phase I-metabolizing enzyme and hormone receptor loci influence
      the response to anti-TNF therapy in rheumatoid arthritis patients.
AB  - The aim of this case-control study was to evaluate whether 47 single-nucleotide
      polymorphisms (SNPs) in steroid hormone-related genes are associated with the
      risk of RA and anti-TNF drug response. We conducted a case-control study in 3
      European populations including 2936 RA patients and 2197 healthy controls. Of
      those, a total of 1985 RA patients were treated with anti-TNF blockers. The
      association of potentially interesting markers in the discovery population was
      validated through meta-analysis with data from DREAM and DANBIO registries.
      Although none of the selected variants had a relevant role in modulating RA risk,
      the meta-analysis of the linear regression data with those from the DREAM and
      DANBIO registries showed a significant correlation of the CYP3A4rs11773597 and
      CYP2C9rs1799853 variants with changes in DAS28 after the administration of anti
      TNF drugs (P = 0.00074 and P = 0.006, respectively). An overall haplotype
      analysis also showed that the ESR2GGG haplotype significantly associated with a
      reduced chance of having poor response to anti-TNF drugs (P = 0.0009). Finally, a
      ROC curve analysis confirmed that a model built with eight steroid hormone
      related variants significantly improved the ability to predict drug response
      compared with the reference model including demographic and clinical variables
      (AUC = 0.633 vs. AUC = 0.556; PLR_test = 1.52 * 10-6). These data together with
      those reporting that the CYP3A4 and ESR2 SNPs correlate with the expression of
      TRIM4 and ESR2 mRNAs in PBMCs (ranging from P = 1.98 * 10-6 to P = 2.0 * 10-35),
      and that the CYP2C9rs1799853 SNP modulates the efficiency of multiple drugs,
      suggest that steroid hormone-related genes may have a role in determining the
      response to anti-TNF drugs.KEY POINTS* Polymorphisms within the CYP3A4 and CYP2C9
      loci correlate with changes in DAS28 after treatment with anti-TNF drugs.* A
      haplotype including eQTL SNPs within the ESR2 gene associates with better
      response to anti-TNF drugs.* A genetic model built with eight steroid hormone
      related variants significantly improved the ability to predict drug response.

PMID- 30287910
TI  - Pharmacogenomics in epithelial ovarian cancer first-line treatment outcome:
      validation of GWAS-associated NRG3 rs1649942 and BRE rs7572644 variants in an
      independent cohort.
AB  - The identification of predictive biomarkers for the first-line treatment of
      epithelial ovarian cancer (EOC) remains a challenge. Although genome-wide
      association studies (GWAS) have identified several genetic polymorphisms as
      predictors of EOC clinical outcome, the subsequent validation has not yet been
      performed. This study aims to validate the influence of Neuregulin 3 (NRG3)
      rs1649942 and Brain and reproductive organ-expressed (TNFRSF1A modulator) (BRE)
      rs7572644 GWAS-identified variants in an independent cohort of EOC patients from
      the North region of Portugal (n = 339) submitted to first-line treatment.
      Polymorphism genotypes were determined by real-time PCR using validated assays.
      Patients carrying the NRG3 rs1649942 A allele presented a significantly longer
      overall survival (OS) when compared to GG-genotype patients (log-rank test, P =
      0.011) in the FIGO IV stage subgroup. No impact was observed for early-stage
      patients or considering disease-free survival (DFS) as an outcome. For FIGO I/II
      stage patients, BRE rs7572644 C allele carriers exhibit a decreased OS (P =
      0.014) and DFS (P = 0.032) when compared to TT-homozygous patients. Furthermore,
      a Multivariate Cox regression analysis revealed a three-fold increase in the risk
      of death (HR, 3.09; P = 0.015) and recurrence (HR, 3.33; P = 0.009) for FIGO I/II
      C allele carriers. No significant impact was observed for late-stage patients.
      The BRE rs7572644 and NRG3 rs1649942 genetic variants were validated in an
      independent cohort of EOC Portuguese patients, particularly in specific subgroups
      considering FIGO staging. Further functional post-GWAS analyses are indispensable
      to understand the biological mechanisms underlying the observed results.

PMID- 30287911
TI  - Association between SOST gene polymorphisms and response to alendronate treatment
      in postmenopausal Chinese women with low bone mineral density.
AB  - The aim of this study was to explore the allelic association between SOST
      polymorphisms and the variance of clinical effects of alendronate in
      postmenopausal Chinese women with osteoporosis or osteopenia. In the study, 500
      postmenopausal women in Shanghai area with osteoporosis or osteopenia were
      included. All participants were treated with weekly oral alendronate 70 mg, daily
      calcium 600 mg and vitamin D 125 IU for 12 months. Nine tagging single-nucleotide
      polymorphisms (SNPs) in SOST gene were genotyped. Bone mineral density of lumbar
      spine (L1-L4), left femoral neck and total hip were measured at baseline and
      after 1 year of treatment, respectively. In the study, 450 subjects completed the
      1-year follow-up. The rs865429 was significantly associated with the % change of
      BMD at the femoral neck (P = 0.007). GG carriers seemed to be at an advantage
      after treatment of alendronate. Compared with AG and AA heterozygote, GG
      homozygote had the highest % change of BMD (3.100 +/- 2.899%) at femoral neck.
      The odds ratio (95% confidence) of GG homozygote to be responders at femoral neck
      was 1.921 (1.211-3.048). Two haplotypes GG and AC constituted by rs865429 and
      rs851057 were associated with the % change of BMD at femoral neck and total hip,
      respectively. Therefore, the common variation of SOST gene contribute to the
      therapeutic response to alendronate treatment in Chinese women with osteoporosis
      or osteopenia.

PMID- 30287912
TI  - Oenological traits of Lachancea thermotolerans show signs of domestication and
      allopatric differentiation.
AB  - The yeast Lachancea thermotolerans (previously Kluyveromyces thermotolerans) is a
      species of large, yet underexplored, oenological potential. This study delivers
      comprehensive oenological phenomes of 94 L. thermotolerans strains obtained from
      diverse ecological niches worldwide, classified in nine genetic groups based on
      their pre-determined microsatellite genotypes. The strains and the genetic groups
      were compared for their alcoholic fermentation performance, production of primary
      and secondary metabolites and pH modulation in Chardonnay grape juice
      fermentations. The common oenological features of L. thermotolerans strains were
      their glucophilic character, relatively extensive fermentation ability, low
      production of acetic acid and the formation of lactic acid, which significantly
      affected the pH of the wines. An untargeted analysis of volatile compounds, used
      for the first time in a population-scale phenotyping of a non-Saccharomyces
      yeast, revealed that 58 out of 90 volatiles were affected at an L. thermotolerans
      strain level. Besides the remarkable extent of intra-specific diversity, our
      results confirmed the distinct phenotypic performance of L. thermotolerans
      genetic groups. Together, these observations provide further support for the
      occurrence of domestication events and allopatric differentiation in L.
      thermotolerans population.

PMID- 30287913
TI  - Ultra-wide-band structural slow light.
AB  - The ability of using integrated photonics to scale multiple optical components on
      a single monolithic chip offers key advantages to create miniature light
      controlling chips. Numerous scaled optical components have been already
      demonstrated. However, present integrated photonic circuits are still rudimentary
      compared to the complexity of today's electronic circuits. Slow light propagation
      in nanostructured materials is a key component for realizing chip-integrated
      photonic devices controlling the relative phase of light and enhancing optical
      nonlinearities. We present an experimental record high group-index-bandwidth
      product (GBP) of 0.47 over a 17.7 nm bandwidth in genetically optimized coupled
      cavity-waveguides (CCWs) formed by L3 photonic crystal cavities. Our structures
      were realized in silicon-on-insulator slabs integrating up to 800 coupled
      cavities, and characterized by transmission, Fourier-space imaging of mode
      dispersion, and Mach-Zehnder interferometry.

PMID- 30287914
TI  - The colorectal cancer epidemic: challenges and opportunities for primary,
      secondary and tertiary prevention.
AB  - Colorectal cancer (CRC) is both one of the most common and one of the most
      preventable cancers globally, with powerful but strongly missed potential for
      primary, secondary and tertiary prevention. CRC incidence has traditionally been
      the highest in affluent Western countries, but it is now increasing rapidly with
      economic development in many other parts of the world. CRC shares several main
      risk factors, such as smoking, excessive alcohol consumption, physical inactivity
      and being overweight, with other common diseases; therefore, primary prevention
      efforts to reduce these risk factors are expected to have multiple beneficial
      effects that extend beyond CRC prevention, and should have high public health
      impact. A sizeable reduction in the incidence and mortality of CRC can also be
      achieved by offering effective screening tests, such as faecal immunochemical
      tests, flexible sigmoidoscopy and colonoscopy, in organised screening programmes
      which have been implemented in an increasing number of countries. Countries with
      early and high uptake rates of effective screening have exhibited major declines
      in CRC incidence and mortality, in contrast to most other countries. Finally,
      increasing evidence shows that the prognosis and quality of life of CRC patients
      can be substantially improved by tertiary prevention measures, such as the
      administration of low-dose aspirin and the promotion of physical activity.

PMID- 30287915
TI  - Hierarchical clustering of activated proteins in the PI3K and MAPK pathways in ER
      positive, HER2-negative breast cancer with potential therapeutic consequences.
AB  - BACKGROUND: The phosphatidylinositol-3-kinase (PI3K) and/or mitogen-activated
      protein kinase (MAPK) pathways are frequently activated in breast cancer which
      can result in antioestrogen resistance. Single protein markers failed to be
      introduced into clinical practice. We, therefore, aimed to find a better read-out
      of activation of the PI3K and MAPK pathways in ER+/HER2- breast cancer.
      Assessment of seven PI3K/MAPK proteins might better reflect pathway activation
      and distinguish patients without adjuvant tamoxifen benefit. METHODS: Tumour
      blocks were recollected from 293 primary postmenopausal ER+/HER2- breast cancer
      patients randomised between tamoxifen and no adjuvant therapy. PTEN, p
      AKT(Thr308), p-AKT(Ser473), p-p70S6K, p-4EBP1, p-ERK1/2 and p-S6RP expression was
      assessed by immunohistochemistry followed by unsupervised hierarchical
      clustering. The primary endpoint was recurrence-free interval. Multivariate Cox
      models were used to assess tamoxifen benefit. A classification tool was developed
      based on protein expression profile. RESULTS: Subgroups were identified with
      preferentially activated (A) and preferentially not activated (N) proteins.
      Patients in group N derived significant benefit from tamoxifen (multivariate
      hazard ratio (HR) = 0.23, p = 0.000101), while patients from group A did not
      (multivariate HR = 1.37, p = 0.64), p for interaction 0.020. Our generated
      classification tool confirmed these results (p for interaction 0.024).
      CONCLUSIONS: Hierarchical clustering of seven PI3K/MAPK proteins reflects pathway
      activation and can guide treatment decisions in primary ER+/HER2- postmenopausal
      breast cancer patients.

PMID- 30287917
TI  - Analysis of cell proliferation and tissue remodelling uncovers a KLF4 activity
      score associated with poor prognosis in colorectal cancer.
AB  - BACKGROUND: Human cancers can be classified based on gene signatures quantifying
      the degree of cell proliferation and tissue remodelling (PR). However, the
      specific factors that drive the increased tissue remodelling in tumours are not
      fully understood. Here we address this question using colorectal cancer as a case
      study. METHODS: We reanalysed a reported cohort of colorectal cancer patients.
      The patients were stratified based on gene signatures of cell proliferation and
      tissue remodelling. Putative transcription factors activity was inferred using
      gene expression profiles and annotations of transcription factor targets as
      input. RESULTS: We demonstrate that the PR classification performs better than
      the currently adopted consensus molecular subtyping (CMS). Although CMS
      classification differentiates patients with a mesenchymal signature, it cannot
      distinguish the remaining patients based on survival. We demonstrate that the
      missing factor is cell proliferation, which is indicative of good prognosis. We
      also uncover a KLF4 transcription factor activity score associated with the
      tissue remodelling gene signature. We further show that the KLF4 activity score
      is significantly higher in colorectal tumours with predicted infiltration of
      cells from the myeloid lineage. CONCLUSION: The KLF4 activity score is associated
      with tissue remodelling, myeloid cell infiltration and poor prognosis in
      colorectal cancer.

PMID- 30287916
TI  - Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumour-associated factors in
      serous ovarian cancer.
AB  - BACKGROUND: Tissue kallikrein-related peptidases 4, 5, 6 and 7 (KLK4-7) strongly
      increase the malignancy of ovarian cancer cells. Deciphering their downstream
      effectors, we aimed at finding new potential prognostic biomarkers and treatment
      targets for ovarian cancer patients. KLK4-7-transfected (OV-KLK4-7) and vector
      control OV-MZ-6 (OV-VC) ovarian cancer cells were established to select
      differentially regulated factors. METHODS: With three independent approaches, PCR
      arrays, genome-wide microarray and proteome analyses, we identified 10 candidates
      (MSN, KRT19, COL5A2, COL1A2, BMP5, F10, KRT7, JUNB, BMP4, MMP1). To determine
      differential protein expression, we performed western blot analyses,
      immunofluorescence and immunohistochemistry for four candidates (MSN, KRT19,
      KRT7, JUNB) in cells, tumour xenograft and patient-derived tissues. RESULTS: We
      demonstrated that KLK4-7 clearly regulates expression of MSN, KRT19, KRT7 and
      JUNB at the mRNA and protein levels in ovarian cancer cells and tissues. Protein
      expression of the top-upregulated effectors, MSN and KRT19, was investigated by
      immunohistochemistry in patients afflicted with serous ovarian cancer and related
      to KLK4-7 immunoexpression. Significant positive associations were found for
      KRT19/KLK4, KRT19/KLK5 and MSN/KLK7. CONCLUSION: These findings imply that KLK4-7
      exert key modulatory effects on other cancer-related genes and proteins in
      ovarian cancer. These downstream effectors of KLK4-7, MSN and KRT19 may represent
      important therapeutic targets in serous ovarian cancer.

PMID- 30287918
TI  - Differences in DNA methylation profiles by histologic subtype of paediatric germ
      cell tumours: a report from the Children's Oncology Group.
AB  - BACKGROUND: Abnormal DNA methylation may be important in germ cell tumour (GCT)
      aetiology, as germ cells undergo complete epigenetic reprogramming during
      development. GCTs show differences in global and promoter methylation patterns by
      histologic subtype. We conducted an epigenome-wide study to identify methylation
      differences by GCT histology. METHODS: Using the Illumina HumanMethylation450K
      array we measured methylation in 154 paediatric GCTs (21
      germinomas/seminomas/dysgerminoma, 70 yolk sac tumours [YST], 9 teratomas, and 54
      mixed histology tumours). We identified differentially methylated regions (DMRs)
      between GCT histologies by comparing methylation beta values. RESULTS: We
      identified 8,481 DMRs (FWER < 0.05). Unsupervised hierarchical clustering of
      individual probes within DMRs resulted in four high level clusters closely
      corresponding to tumour histology. Clusters corresponding to age, location, sex
      and FFPE status were not observed within these DMRs. Germinomas displayed lower
      levels of methylation across the DMRs relative to the other histologic subtypes.
      Pathway analysis on the top 10% of genes with differential methylation in
      germinomas/seminomas/dysgerminoma compared to YST suggested angiogenesis and
      immune cell-related pathways displayed decreased methylation in
      germinomas/seminomas/dysgerminoma relative to YST. CONCLUSIONS: Paediatric GCT
      histologies have differential methylation patterns. The genes that are
      differentially methylated may provide insights into GCT aetiology including the
      timing of GCT initiation.

PMID- 30287919
TI  - Targeting peroxiredoxin 1 impairs growth of breast cancer cells and potently
      sensitises these cells to prooxidant agents.
AB  - BACKGROUND: Our previous work has shown peroxiredoxin-1 (PRDX1), one of major
      antioxidant enzymes, to be a biomarker in human breast cancer. Hereby, we further
      investigate the role of PRDX1, compared to its close homolog PRDX2, in mammary
      malignant cells. METHODS: CRISPR/Cas9- or RNAi-based methods were used for
      genetic targeting PRDX1/2. Cell growth was assessed by crystal violet, EdU
      incorporation or colony formation assays. In vivo growth was assessed by a
      xenotransplantation model. Adenanthin was used to inhibit the thioredoxin
      dependent antioxidant defense system. The prooxidant agents used were hydrogen
      peroxide, glucose oxidase and sodium L-ascorbate. A PY1 probe or HyPer-3
      biosensor were used to detect hydrogen peroxide content in samples. RESULTS:
      PRDX1 downregulation significantly impaired the growth rate of MCF-7 and ZR-75-1
      breast cancer cells. Likewise, xenotransplanted PRDX1-deficient MCF-7 cells
      presented a retarded tumour growth. Furthermore, genetic targeting of PRDX1 or
      adenanthin, but not PRDX2, potently sensitised all six cancer cell lines studied,
      but not the non-cancerous cells, to glucose oxidase and ascorbate. CONCLUSIONS:
      Our study pinpoints the dominant role for PRDX1 in management of exogeneous
      oxidative stress by breast cancer cells and substantiates further exploration of
      PRDX1 as a target in this disease, especially when combined with prooxidant
      agents.

PMID- 30287921
TI  - Author Correction: Intravenous fluid therapy in critically ill adults.
AB  - Corrections: Fig. 1: 'MAP' inserted before '60-65 mmHg; Fig. 3:
      'Echocardiography' amended to 'Electrocardiographic'. Fig. 4b additions: two cell
      nuclei; text labels 'Large pore transporting plasma proteins', 'Small pore
      network', 'Intercellular cleft'; 'Intact' and 'Damaged'; legend updated.

PMID- 30287920
TI  - A Clinical Risk Prediction Tool for Peritonitis-Associated Treatment Failure in
      Peritoneal Dialysis Patients.
AB  - A tool to predict peritonitis-associated treatment failure among peritoneal
      dialysis (PD) patients has not yet been established. We conducted a multicentre,
      retrospective cohort study among 1,025 PD patients between 2006 and 2016 in
      Thailand to develop and internally validate such a tool. Treatment failure was
      defined as either a requirement for catheter removal, a switch to haemodialysis,
      or peritonitis-associated mortality. Prediction model performances were analysed
      using discrimination (C-statistics) and calibration (Hosmer-Lemeshow test) tests.
      Predictors were weighted to calculate a risk score. In total, 435 patients with
      855 episodes of peritonitis were identified; 215 (25.2%) episodes resulted in
      treatment failure. A total risk score of 11.5 was developed including, diabetes,
      systolic blood pressure <90 mmHg, and dialysate leukocyte count >1,000/mm3 and
      >100/mm3 on days 3-4 and day 5, respectively. The discrimination (C-statistic =
      0.92; 95%CI, 0.89-0.94) and calibration (P > 0.05) indicated an excellent
      performance. No significant difference was observed in the internal validation
      cohort. The rate of treatment failure in the different groups was 3.0% (low-risk,
      <1.5 points), 54.4% (moderate-risk, 1.5-9 points), and 89.5% (high-risk, >9
      points). A simplified risk-scoring scheme to predict treatment failure may be
      useful for clinical decision making regarding PD patients with peritonitis.
      External validation studies are needed.

PMID- 30287922
TI  - Secondary findings from clinical genomic sequencing: prevalence, patient
      perspectives, family history assessment, and health-care costs from a multisite
      study.
AB  - PURPOSE: Clinical sequencing emerging in health care may result in secondary
      findings (SFs). METHODS: Seventy-four of 6240 (1.2%) participants who underwent
      genome or exome sequencing through the Clinical Sequencing Exploratory Research
      (CSER) Consortium received one or more SFs from the original American College of
      Medical Genetics and Genomics (ACMG) recommended 56 gene-condition pair list; we
      assessed clinical and psychosocial actions. RESULTS: The overall adjusted
      prevalence of SFs in the ACMG 56 genes across the CSER consortium was 1.7%.
      Initially 32% of the family histories were positive, and post disclosure, this
      increased to 48%. The average cost of follow-up medical actions per finding up to
      a 1-year period was $128 (observed, range: $0-$678) and $421 (recommended, range:
      $141-$1114). Case reports revealed variability in the frequency of and follow-up
      on medical recommendations patients received associated with each SF gene
      condition pair. Participants did not report adverse psychosocial impact
      associated with receiving SFs; this was corroborated by 18 participant (or
      parent) interviews. All interviewed participants shared findings with relatives
      and reported that relatives did not pursue additional testing or care.
      CONCLUSION: Our results suggest that disclosure of SFs shows little to no adverse
      impact on participants and adds only modestly to near-term health-care costs;
      additional studies are needed to confirm these findings.

PMID- 30287923
TI  - Standard operating procedure for somatic variant refinement of sequencing data
      with paired tumor and normal samples.
AB  - PURPOSE: Following automated variant calling, manual review of aligned read
      sequences is required to identify a high-quality list of somatic variants.
      Despite widespread use in analyzing sequence data, methods to standardize manual
      review have not been described, resulting in high inter- and intralab
      variability. METHODS: This manual review standard operating procedure (SOP)
      consists of methods to annotate variants with four different calls and 19 tags.
      The calls indicate a reviewer's confidence in each variant and the tags indicate
      commonly observed sequencing patterns and artifacts that inform the manual review
      call. Four individuals were asked to classify variants prior to, and after,
      reading the SOP and accuracy was assessed by comparing reviewer calls with
      orthogonal validation sequencing. RESULTS: After reading the SOP, average
      accuracy in somatic variant identification increased by 16.7% (p value = 0.0298)
      and average interreviewer agreement increased by 12.7% (p value < 0.001). Manual
      review conducted after reading the SOP did not significantly increase reviewer
      time. CONCLUSION: This SOP supports and enhances manual somatic variant detection
      by improving reviewer accuracy while reducing the interreviewer variability for
      variant calling and annotation.

PMID- 30287924
TI  - Putting genome-wide sequencing in neonates into perspective.
AB  - PURPOSE: Several studies have reported diagnostic yields up to 57% for rapid
      exome or genome sequencing (rES/GS) as a single test in neonatal intensive care
      unit (NICU) patients, but the additional yield of rES/GS compared with other
      available diagnostic options still remains unquantified in this population.
      METHODS: We retrospectively evaluated all genetic NICU consultations in a 2-year
      period. RESULTS: In 132 retrospectively evaluated NICU consultations 27 of 32
      diagnoses (84.4%) were made using standard genetic workup. Most diagnoses (65.6%)
      were made within 16 days. Diagnostic ES yield was 5/29 (17.2%). Genetic diagnoses
      had a direct effect on clinical management in 90.6% (29/32) of patients.
      CONCLUSIONS: Our study shows that exome sequencing has a place in NICU
      diagnostics, but given the associated costs and the high yield of alternative
      diagnostic strategies, we recommend to first perform clinical genetic
      consultation.

PMID- 30287926
TI  - Histiocyte-rich rhabdomyoblastic tumor: rhabdomyosarcoma, rhabdomyoma, or
      rhabdomyoblastic tumor of uncertain malignant potential? A histologically
      distinctive rhabdomyoblastic tumor in search of a place in the classification of
      skeletal muscle neoplasms.
AB  - Skeletal muscle tumors are traditionally classified as rhabdomyoma or
      rhabdomyosarcoma. We have identified an unusual adult rhabdomyoblastic tumor not
      clearly corresponding to a previously described variant of rhabdomyoma or
      rhabdomyosarcoma, characterized by a very striking proliferation of non
      neoplastic histiocytes, obscuring the underlying tumor. Ten cases were identified
      in nine males and one female with a median age of 43 years (range 23-69 years).
      Tumors involved the deep soft tissues of the trunk (N = 4), lower limbs (N = 4),
      and neck (N = 2). Tumors were well-circumscribed, nodular masses, frequently
      surrounded by a fibrous capsule containing lymphoid aggregates and sometimes
      calcifications. Numerous foamy macrophages, multinucleated Touton-type giant
      cells, and sheets/fascicles of smaller, often spindled macrophages largely
      obscured the underlying desmin, MyoD1, and myogenin-positive rhabdomyoblastic
      tumor. Cases were wild type for MYOD1 and no other mutations or rearrangements
      characteristic of a known subtype of rhabdomyoma or rhabdomyosarcoma were
      identified. Two of four cases successfully analyzed using a next-generation
      sequencing panel of 170 common cancer-related genes harbored inactivating NF1
      mutations. Next-generation sequencing showed no gene fusions. Clinical follow
      (nine patients; median 9 months; mean 23 months; range 3-124 months) showed all
      patients received wide excision; four patients also received adjuvant
      radiotherapy and none received chemotherapy. At the time of last follow-up, all
      patients were alive and without disease; no local recurrences or distant
      metastases occurred. We hypothesize that these unusual tumors represent
      rhabdomyoblastic tumors of uncertain malignant potential. Possibly over time they
      should be relegated to a new category of skeletal muscle tumors of intermediate
      (borderline) malignancy.

PMID- 30287925
TI  - Variants affecting diverse domains of MEPE are associated with two distinct bone
      disorders, a craniofacial bone defect and otosclerosis.
AB  - PURPOSE: To characterize new molecular factors implicated in a hereditary
      congenital facial paresis (HCFP) family and otosclerosis. METHODS: We performed
      exome sequencing in a four-generation family presenting nonprogressive HCFP and
      mixed hearing loss (HL). MEPE was analyzed using either Sanger sequencing or
      molecular inversion probes combined with massive parallel sequencing in 89
      otosclerosis families, 1604 unrelated affected subjects, and 1538 unscreened
      controls. RESULTS: Exome sequencing in the HCFP family led to the identification
      of a rare segregating heterozygous frameshift variant p.(Gln425Lysfs*38) in MEPE.
      As the HL phenotype in this family resembled otosclerosis, we performed variant
      burden and variance components analyses in a large otosclerosis cohort and
      demonstrated that nonsense and frameshift MEPE variants were significantly
      enriched in affected subjects (p = 0.0006-0.0060). CONCLUSION: MEPE exerts its
      function in bone homeostasis by two domains, an RGD and an acidic serine
      aspartate-rich MEPE-associated (ASARM) motif inhibiting respectively bone
      resorption and mineralization. All variants associated with otosclerosis are
      predicted to result in nonsense mediated decay or an ASARM-and-RGD-truncated
      MEPE. The HCFP variant is predicted to produce an ASARM-truncated MEPE with an
      intact RGD motif. This difference in effect on the protein corresponds with the
      presumed pathophysiology of both diseases, and provides a plausible molecular
      explanation for the distinct phenotypic outcome.

PMID- 30287928
TI  - Nrf2 mediates the resistance of human A549 and HepG2 cancer cells to boningmycin,
      a new antitumor antibiotic, in vitro through regulation of glutathione levels.
AB  - NF-E2-related factor 2 (Nrf2) is a transcription factor and a pivotal factor in
      the induction of the cell defense system. Recent reports show that Nrf2 plays
      critical roles in tumor heterogeneity and drug resistance. In the present study
      we investigated whether and how Nrf2 mediated the resistance of human cancer
      cells to boningmycin (BON), a new antitumor antibiotic of the bleomycin family.
      We showed that in the expression levels of Nrf2 in human non-small lung cancer
      A549 cells were much higher than those in human hepatoblastoma HepG2 cells, and
      their resistance to BON was opposite to Nrf2 expression (the IC50values of BON in
      A549 cells and HepG2 cells were 5.97 and 0.61 MUmol/L, respectively). Similar
      results were observed with the anticancer agent cisdiamminedichloroplatinum
      (DDP), which was used as a positive control. In A549 cells, Nrf2 mRNA knockdown
      significantly increased their susceptibilities to BON and DDP. An enhanced
      resistance to BON and DDP was observed in HepG2 cells after overexpression of the
      wild-type Nrf2 protein. Treatment with a specific Nrf2 inhibitor, luteolin,
      significantly sensitized A549 cells to BON and DDP and increased BON- or DDP
      induced apoptosis. The total levels of glutathione (GSH), the final product of
      the Nrf2 signaling pathway, were much higher in A549 cells than those in HepG2
      cells. Supplementation of GSH in HepG2 cells significantly decreased their
      susceptibility to BON and DDP, wheras depleting GSH with the specific inhibitor L
      buthionine sulfoximine in A549 cells significantly increased their susceptibility
      to BON and DDP. Our results demonstrate that Nrf2 mediates the resistance to BON
      through regulating glutathione levels in A549 cells and HepG2 cells.

PMID- 30287929
TI  - High-throughput ab initio calculations on dielectric constant and band gap of non
      oxide dielectrics.
AB  - High-k dielectrics, materials having a large band gap (Eg) and high dielectric
      constant (k) simultaneously, constitute critical components in microelectronic
      devices. Because of the inverse relationship between Eg and k, materials with
      large values in both properties are rare. Therefore, massive databases on Eg and
      k will be useful in identifying optimal high-k materials. While experimental and
      theoretical data on Eg and k of oxides are accumulating, corresponding
      information is scarce for non-oxide dielectrics with anions such as C, N, F, P,
      S, and Cl. To identify promising high-k dielectrics among these material groups,
      we screen 869 compounds of binary carbides, nitrides, sulfides, phosphides,
      chlorides, and fluorides, through automated ab initio calculations. Among these
      compounds, fluorides exhibit an Eg-k relation that is comparable to that of
      oxides. By further screening over ternary fluorides, we identify fluorides such
      as BiF3, LaF3, and BaBeF4 that could serve as useful high-k dielectrics.

PMID- 30287927
TI  - Laboratory diagnostics of murine blood for detection of mouse cytomegalovirus
      (MCMV)-induced hepatitis.
AB  - Mouse models are important and versatile tools to study mechanisms and novel
      therapies of human disease in vivo. Both, the number and the complexity of murine
      models are constantly increasing and modification of genes of interest as well as
      any exogenous challenge may lead to unanticipated biological effects. Laboratory
      diagnostics of blood samples provide a comprehensive and rapid screening for
      multiple organ function and are fundamental to detect human disease. Here, we
      adapt an array of laboratory medicine-based tests commonly used in humans to
      establish a platform for standardized, multi-parametric, and quality-controlled
      diagnostics of murine blood samples. We determined sex-dependent reference
      intervals of 51 commonly used laboratory medicine tests for samples obtained from
      the C57BL/6J mouse strain. As a proof of principle, we applied these diagnostic
      tests in a mouse cytomegalovirus (MCMV) infection model to screen for organ
      damage. Consistent with histopathological findings, plasma concentrations of
      liver-specific enzymes were elevated, supporting the diagnosis of a virus-induced
      hepatitis. Plasma activities of aminotransferases correlated with viral loads in
      livers at various days after MCMV infection and discriminated infected from non
      infected animals. This study provides murine blood reference intervals of common
      laboratory medicine parameters and illustrates the use of these tests for
      diagnosis of infectious disease in experimental animals.

PMID- 30287931
TI  - Publisher Correction: Image Data Resource: a bioimage data integration and
      publication platform.
AB  - This paper was originally published under standard Nature America Inc. copyright.
      As of the date of this correction, the Resource is available online as an open
      access paper with a CC-BY license. No other part of the paper has been changed.

PMID- 30287930
TI  - Fast robust dose calculation on GPU for high-precision 1H, 4He, 12C and 16O ion
      therapy: the FRoG platform.
AB  - Radiotherapy with protons and heavier ions landmarks a novel era in the field of
      high-precision cancer therapy. To identify patients most benefiting from this
      technologically demanding therapy, fast assessment of comparative treatment plans
      utilizing different ion species is urgently needed. Moreover, to overcome
      uncertainties of actual in-vivo physical dose distribution and biological effects
      elicited by different radiation qualities, development of a reliable high
      throughput algorithm is required. To this end, we engineered a unique graphics
      processing unit (GPU) based software architecture allowing rapid and robust dose
      calculation. FRoG, Fast Recalculation on GPU, currently operates with four
      particle beams available at Heidelberg Ion Beam Therapy center, i.e., raster
      scanning proton (1H), helium (4He), carbon (12C) and oxygen ions (16O). FRoG
      enables comparative analysis of different models for estimation of physical and
      biological effective dose in 3D within minutes and in excellent agreement with
      the gold standard Monte Carlo (MC) simulation. This is a crucial step towards
      development of next-generation patient specific radiotherapy.

PMID- 30287933
TI  - Structural and functional body components in athletic health and performance
      phenotypes.
AB  - Advances in body composition assessment enable a detailed body composition
      analyses and the respective organization at different levels. Sports-related
      professionals are interested in understanding how and which body components are
      relevant for improving performance, prevent injury risk, and monitor athletic
      health. The aim of this review is to propose an integrative model that links
      performance, injury risk, and athletic health with body components, and to report
      their cross-sectional and longitudinal associations. Cross-sectional studies
      reveal that endurance athletes with higher fat mass (FM) show a longer race time,
      whereas a higher fat-free mass benefits power and strength-related tasks.
      Longitudinal studies indicated that increases in intracellular water, assessed
      through dilution techniques, were associated with power and strength
      improvements, independently of weight and lean-soft-tissue changes. There is
      evidence that athletes involved in weight-sensitive sports restrict energy
      intake, thus reducing energy availability (EA) and compromising bone health
      (Female Athlete Triad). To counteract the low EA and related negative energy
      balance, metabolic adaption (MA) occurs to promote energy conservation.
      Currently, reference values for body composition assessment using anthropometry
      and DXA are available for a few sports, according to sex. More research is needed
      to develop a functional body composition profile according to sports-specific
      requirements.

PMID- 30287932
TI  - Ex vivo assessment and in vivo validation of non-invasive stent monitoring
      techniques based on microwave spectrometry.
AB  - Some conditions are well known to be directly associated with stent failure,
      including in-stent re-occlusion and stent fracture. Currently, identification of
      these high-risk conditions requires invasive and complex procedures. This study
      aims to assess microwave spectrometry (MWS) for monitoring stents non-invasively.
      Preliminary ex vivo data are presented to move to in vivo validation. Fifteen
      mice were assigned to receive subcutaneous stent implantations (n = 10) or sham
      operations (n = 5). MWS measurements were carried out at 0, 2, 4, 7, 14, 22, and
      29 days of follow-up. Additionally, 5 stented animals were summited to micro-CT
      analyses at the same time points. At 29 days, 3 animals were included into a
      stent fracture subgroup and underwent a last MWS and micro-CT analysis. MWS was
      able to identify stent position and in-stent stenosis over time, also discerning
      significant differences from baseline measures (P < 0.001). Moreover, MWS
      identified fractured vs. non-fractured stents in vivo. Taken together, MWS
      emerges as a non-invasive, non-ionizing alternative for stent monitoring. MWS
      analysis clearly distinguished between in-stent stenosis and stent fracture
      phenomena.

PMID- 30287934
TI  - Association between Geriatric Nutrition Risk Index and low muscle mass in Chinese
      elderly people.
AB  - BACKGROUND/OBJECTIVES: The aim of the study was to evaluate the relationship
      between Geriatric Nutrition Risk Index (GNRI) and low muscle mass (LMM) in
      elderly people. SUBJECTS/METHODS: A cross-sectional study was carried out in
      Chinese PLA General Hospital with 3240 participants who underwent a health check
      up examination between February 2016 and February 2017. Linear regression and
      logistic regression were used to examine the relationship between GNRI and LMM.
      RESULTS: The mean age of the participants in the study was 64.6 years. The mean
      appendicular skeletal muscle mass index (ASMI) was 8.92 +/- 0.93 kg/m2 in men and
      7.62 +/- 0.73 kg/m2 in women. The incidences of LMM were 7.9% in men and 3.7% in
      women. Linear regression demonstrated that GNRIs were positively correlated with
      ASMIs in both men and women (beta = 0.055 for men and 0.039 for women, all P <
      0.001). The cut-off point of the GNRI in elderly people for LMM was 104.0 in men
      and 107.0 in women and were identified by Classification and Regression Trees
      (CART). Logistic regression showed that both men and women with decreased GNRIs
      had higher ratios of LMM [odds ratio (OR) = 3.904 for men and 4.486 for women, P
      < 0.001 and P = 0.001, respectively]. CONCLUSIONS: Elderly people with a low GNRI
      had a higher incidence of LMM, which suggested that GNRI had a close relationship
      with LMM and that it could be a good indicator in identifying senior people who
      need further nutritional support and physical activity.

PMID- 30287935
TI  - The biology and treatment of Merkel cell carcinoma: current understanding and
      research priorities.
AB  - Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer associated with
      advanced age and immunosuppression. Over the past decade, an association has been
      discovered between MCC and either integration of the Merkel cell polyomavirus,
      which likely drives tumorigenesis, or somatic mutations owing to ultraviolet
      induced DNA damage. Both virus-positive and virus-negative MCCs are immunogenic,
      and inhibition of the programmed cell death protein 1 (PD-1)-programmed cell
      death 1 ligand 1 (PD-L1) immune checkpoint has proved to be highly effective in
      treating patients with metastatic MCC; however, not all patients have a durable
      response to immunotherapy. Despite these rapid advances in the understanding and
      management of patients with MCC, many basic, translational and clinical research
      questions remain unanswered. In March 2018, an International Workshop on Merkel
      Cell Carcinoma Research was held at the US National Cancer Institute, at which
      academic, government and industry experts met to identify the highest-priority
      research questions. Here, we review the biology and treatment of MCC and report
      the consensus-based recommendations agreed upon during the workshop.

PMID- 30287936
TI  - Feasibility of Venetoclax-based combinations for adult patients with acute
      myeloid leukemia relapsing after allogenic stem cell transplantation.

PMID- 30287938
TI  - Non-invasive measurement of sclerosis in cutaneous cGVHD patients with the
      handheld device Myoton: a cross-sectional study.

PMID- 30287937
TI  - HBV reactivation after hematopoietic stem cell transplantation and rituximab
      containing chemotherapy: a 12-year experience at a single center.

PMID- 30287939
TI  - Employment status was highly associated with quality of life after allogeneic
      hematopoietic cell transplantation, and the association may differ according to
      patient age and graft-versus-host disease status: analysis of a nationwide QOL
      survey.

PMID- 30287940
TI  - Humanization of Antibodies using a Statistical Inference Approach.
AB  - Antibody humanization is a key step in the preclinical phase of the development
      of therapeutic antibodies, originally developed and tested in non-human models
      (most typically, in mouse). The standard technique of Complementarity-Determining
      Regions (CDR) grafting into human Framework Regions of germline sequences has
      some important drawbacks, in that the resulting sequences often need further back
      mutations to ensure functionality and/or stability. Here we propose a new method
      to characterize the statistical distribution of the sequences of the variable
      regions of human antibodies, that takes into account phenotypical correlations
      between pairs of residues, both within and between chains. We define a "humanness
      score" of a sequence, comparing its performance in distinguishing human from
      murine sequences, with that of some alternative scores in the literature. We also
      compare the score with the experimental immunogenicity of clinically used
      antibodies. Finally, we use the humanness score as an optimization function and
      perform a search in the sequence space, starting from different murine sequences
      and keeping the CDR regions unchanged. Our results show that our humanness score
      outperforms other methods in sequence classification, and the optimization
      protocol is able to generate humanized sequences that are recognized as human by
      standard homology modelling tools.

PMID- 30287941
TI  - The Long-term Outcome After Resection of Upper Cervical Spinal Cord Tumors:
      Report of 51 Consecutive Cases.
AB  - The literature discussing the long-term outcome after resection of upper cervical
      spinal cord tumors is limited. The purpose of this study was to review the
      progression-free survival (PFS), overall survival (OS), and long-term outcomes in
      a consecutive series of 51 patients with upper cervical spinal cord tumors who
      underwent surgery at our institution between 2005 and 2010. Patient outcome were
      evaluated using the Japanese Orthopaedic Association score (JOA) and the
      McCormick functional schema. Follow-up data was collected completely and the
      median follow-up time was 6.1 years. Gross total resection (GTR) was performed in
      27 patients (52.94%) and subtotal resection (STR) in 24 patients (47.06%).
      Progression-free survival and overall survival at 5 years was 88.23% and 92.16%,
      respectively. Good prognosis was defined as 74.51% based on JOA scoring. The
      univariate analysis showed that patients over 60y, tumors located higher than C2,
      tumor size greater than 4 cm as well as malignant tumors and subtotal resection
      were factors indicating a poor prognosis. However, the multivariate regression
      analyses showed only the level of tumor and tumor size were independent risk
      factors for a poor prognosis. The gold standard treatment for intraspinal tumors
      is gross total resection and follow-up should be focused on patients with a high
      risk of poor prognosis.

PMID- 30287942
TI  - Tom20 senses iron-activated ROS signaling to promote melanoma cell pyroptosis.
AB  - Iron has been shown to trigger oxidative stress by elevating reactive oxygen
      species (ROS) and to participate in different modes of cell death, such as
      ferroptosis, apoptosis and necroptosis. However, whether iron-elevated ROS is
      also linked to pyroptosis has not been reported. Here, we demonstrate that iron
      activated ROS can induce pyroptosis via a Tom20-Bax-caspase-GSDME pathway. In
      melanoma cells, iron enhanced ROS signaling initiated by CCCP, causing the
      oxidation and oligomerization of the mitochondrial outer membrane protein Tom20.
      Bax is recruited to mitochondria by oxidized Tom20, which facilitates cytochrome
      c release to cytosol to activate caspase-3, eventually triggering pyroptotic
      death by inducing GSDME cleavage. Therefore, ROS acts as a causative factor and
      Tom20 senses ROS signaling for iron-driven pyroptotic death of melanoma cells.
      Since iron activates ROS for GSDME-dependent pyroptosis induction and melanoma
      cells specifically express a high level of GSDME, iron may be a potential
      candidate for melanoma therapy. Based on the functional mechanism of iron shown
      above, we further demonstrate that iron supplementation at a dosage used in iron
      deficient patients is sufficient to maximize the anti-tumor effect of clinical
      ROS-inducing drugs to inhibit xenograft tumor growth and metastasis of melanoma
      cells through GSDME-dependent pyroptosis. Moreover, no obvious side effects are
      observed in the normal tissues and organs of mice during the combined treatment
      of clinical drugs and iron. This study not only identifies iron as a sensitizer
      amplifying ROS signaling to drive pyroptosis, but also implicates a novel iron
      based intervention strategy for melanoma therapy.

PMID- 30287944
TI  - Author Correction: Non-flammable electrolyte enables Li-metal batteries with
      aggressive cathode chemistries.
AB  - In the version of this Article originally published, in the first paragraph of
      the Methods, HFE was incorrectly given as 2,2,2-Trifluoroethyl-3',3',3',2',2'
      pentafluoropropyl ether; it should have been 1,1,2,2-tetrafluoroethyl-2',2',2'
      trifluoroethyl ether. This has now been corrected in the online versions of the
      Article.

PMID- 30287943
TI  - Conscious processing of auditory regularities induces a pupil dilation.
AB  - Pupil dilation has been reliably identified as a physiological marker of
      consciously reportable mental effort. This classical finding raises the question
      of whether or not pupil dilation could be a specific somatic signature of
      conscious processing. In order to explore this possibility, we engaged healthy
      volunteers in the 'local global' auditory paradigm we previously designed to
      disentangle conscious from non-conscious processing of novelty. We discovered
      that consciously reported violations of global (inter-trials) regularity were
      associated with a pupil dilation effect both in an active counting task and in a
      passive attentive task. This pupil dilation effect was detectable both at the
      group-level and at the individual level. In contrast, unreported violations of
      this global regularity, as well as unreported violations of local (intra-trial)
      regularity that do not require conscious access, were not associated with a pupil
      dilation effect. We replicated these findings in a phonemic version of the 'local
      global'. Taken together these results strongly suggest that pupil dilation is a
      somatic marker of conscious access in the auditory modality, and that it could
      therefore be used to easily probe conscious processing at the individual level
      without interfering with participant's stream of consciousness by questioning
      him/her.

PMID- 30287945
TI  - Notch and interacting signalling pathways in cardiac development, disease, and
      regeneration.
AB  - Cardiogenesis is a complex developmental process involving multiple overlapping
      stages of cell fate specification, proliferation, differentiation, and
      morphogenesis. Precise spatiotemporal coordination between the different
      cardiogenic processes is ensured by intercellular signalling crosstalk and tissue
      tissue interactions. Notch is an intercellular signalling pathway crucial for
      cell fate decisions during multicellular organismal development and is aptly
      positioned to coordinate the complex signalling crosstalk required for
      progressive cell lineage restriction during cardiogenesis. In this Review, we
      describe the role of Notch signalling and the crosstalk with other signalling
      pathways during the differentiation and patterning of the different cardiac
      tissues and in cardiac valve and ventricular chamber development. We examine how
      perturbation of Notch signalling activity is linked to congenital heart diseases
      affecting the neonate and adult, and discuss studies that shed light on the role
      of Notch signalling in heart regeneration and repair after injury.

PMID- 30287946
TI  - The role of adipose tissue in cardiovascular health and disease.
AB  - Accumulating knowledge on the biology and function of the adipose tissue has led
      to a major shift in our understanding of its role in health and disease. The
      adipose tissue is now recognized as a crucial regulator of cardiovascular health,
      mediated by the secretion of several bioactive products, including
      adipocytokines, microvesicles and gaseous messengers, with a wide range of
      endocrine and paracrine effects on the cardiovascular system. The adipose tissue
      function and secretome are tightly controlled by complex homeostatic mechanisms
      and local cell-cell interactions, which can become dysregulated in obesity.
      Systemic or local inflammation and insulin resistance lead to a shift in the
      adipose tissue secretome from anti-inflammatory and anti-atherogenic towards a
      pro-inflammatory and pro-atherogenic profile. Moreover, the interplay between the
      adipose tissue and the cardiovascular system is bidirectional, with vascular
      derived and heart-derived signals directly affecting adipose tissue biology. In
      this Review, we summarize the current knowledge of the biology and regional
      variability of adipose tissue in humans, deciphering the complex molecular
      mechanisms controlling the crosstalk between the adipose tissue and the
      cardiovascular system, and their possible clinical translation. In addition, we
      highlight the latest developments in adipose tissue imaging for cardiovascular
      risk stratification and discuss how therapeutic targeting of the adipose tissue
      can improve prevention and treatment of cardiovascular disease.

PMID- 30287947
TI  - Kinases everywhere.

PMID- 30287948
TI  - Overexpressing the most abundant enzyme.

PMID- 30287949
TI  - Overexpression of Rubisco subunits with RAF1 increases Rubisco content in maize.
AB  - Rubisco catalyses a rate-limiting step in photosynthesis and has long been a
      target for improvement due to its slow turnover rate. An alternative to modifying
      catalytic properties of Rubisco is to increase its abundance within C4 plant
      chloroplasts, which might increase activity and confer a higher carbon
      assimilation rate. Here, we overexpress the Rubisco large (LS) and small (SS)
      subunits with the Rubisco assembly chaperone RUBISCO ASSEMBLY FACTOR 1 (RAF1).
      While overexpression of LS and/or SS had no discernable impact on Rubisco
      content, addition of RAF1 overexpression resulted in a >30% increase in Rubisco
      content. Gas exchange showed a 15% increase in CO2 assimilation (ASAT) in UBI
      LSSS-RAF1 transgenic plants, which correlated with increased fresh weight and in
      vitro Vcmax calculations. The divergence of Rubisco content and assimilation
      could be accounted for by the Rubisco activation state, which decreased up to
      23%, suggesting that Rubisco activase may be limiting Vcmax, and impinging on the
      realization of photosynthetic potential from increased Rubisco content.

PMID- 30287950
TI  - Bias in resistance gene prediction due to repeat masking.
AB  - Several recently published Brassicaceae genome annotations show strong
      differences in resistance (R)-gene content. We believe that this is caused by
      different approaches to repeat masking. Here we show that some of the repeats
      stored in public databases used for repeat masking carry pieces of predicted R
      gene-related domains, and demonstrate that at least some of the variance in R
      gene content in recent genome annotations is caused by using these repeats for
      repeat masking. We also show that other classes of genes are less affected by
      this phenomenon, and estimate a false positive rate of R genes (0 to 4.6%) that
      are in reality transposons carrying the R-gene domains. These results may
      partially explain why there has been a decrease in published novel R genes in
      recent years, which has implications for plant breeding, especially in the face
      of pathogens changing as a response to climate change.

PMID- 30287952
TI  - The taming of the shrub.

PMID- 30287951
TI  - Structural basis for brassinosteroid response by BIL1/BZR1.
AB  - BRZ-INSENSITIVE-LONG HYPOCOTYL 1 (BIL1)/BRASSINAZOLE-RESISTANT 1 (BZR1) is a
      master transcription factor of brassinosteroid (BR) signalling. The varieties of
      nucleobase recognition of the NN-BRRE-core motif (NNCGTG), one of variant G-box
      motifs, distinguish BIL1/BZR1 from basic helix-loop-helix transcription factors,
      underlying the specific regulation of BR-responsive genes. Here, we show the non
      canonical bHLH dimer formation of BIL1/BZR1 to optimize the interaction network
      with DNA and the orientation of a key residue for NN-BRRE-core motif recognition.

PMID- 30287953
TI  - Primary walls in second place.

PMID- 30287955
TI  - The roots of culture.

PMID- 30287954
TI  - Complete substitution of a secondary cell wall with a primary cell wall in
      Arabidopsis.
AB  - The bulk of a plant's biomass, termed secondary cell walls, accumulates in woody
      xylem tissues and is largely recalcitrant to biochemical degradation and
      saccharification1. By contrast, primary cell walls, which are chemically
      distinct, flexible and generally unlignified2, are easier to deconstruct. Thus,
      engineering certain primary wall characteristics into xylem secondary walls would
      be interesting to readily exploit biomass for industrial processing. Here, we
      demonstrated that by expressing AP2/ERF transcription factors from group IIId and
      IIIe in xylem fibre cells of mutants lacking secondary walls, we could generate
      plants with thickened cell wall characteristics of primary cell walls in the
      place of secondary cell walls. These unique, newly formed walls displayed
      physicochemical and ultrastructural features consistent with primary walls and
      had gene expression profiles illustrative of primary wall synthesis. These data
      indicate that the group IIId and IIIe AP2/ERFs are transcription factors
      regulating primary cell wall deposition and could form the foundation for
      exchanging one cell wall type for another in plants.

PMID- 30287956
TI  - Nutritious corn.

PMID- 30287957
TI  - Rapid improvement of domestication traits in an orphan crop by genome editing.
AB  - Genome editing holds great promise for increasing crop productivity, and there is
      particular interest in advancing breeding in orphan crops, which are often
      burdened by undesirable characteristics resembling wild relatives. We developed
      genomic resources and efficient transformation in the orphan Solanaceae crop
      'groundcherry' (Physalis pruinosa) and used clustered regularly interspaced short
      palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (Cas9) (CRISPR
      Cas9) to mutate orthologues of tomato domestication and improvement genes that
      control plant architecture, flower production and fruit size, thereby improving
      these major productivity traits. Thus, translating knowledge from model crops
      enables rapid creation of targeted allelic diversity and novel breeding germplasm
      in distantly related orphan crops.

PMID- 30287958
TI  - Valuing trees for aesthetics.

PMID- 30287960
TI  - Reply to 'The Green Revolution did not increase poverty and hunger for millions'.

PMID- 30287959
TI  - An indoor rice model.

PMID- 30287961
TI  - The Green Revolution did not increase poverty and hunger for millions.

PMID- 30287962
TI  - Five steps to flabby ridge success.
AB  - Patients presenting with flabby or displaceable tissue continue to challenge even
      the most competent dental practitioners. Under compression, the denture bearing
      area will exhibit localised mobility around the flabby tissue. Selective
      impression techniques have long been used in such cases, ensuring the
      displaceable tissue is recorded 'at rest'. Subsequently, the denture will
      maintain its peripheral seal during function. This article will describe five
      steps in maximising the success when producing a retentive and stable removable
      prosthesis for flabby ridges.

PMID- 30287964
TI  - Developing understanding and enactment of professionalism: undergraduate dental
      students' perceptions of influential experiences in this process.

PMID- 30287965
TI  - Interviews and focus groups in qualitative research: an update for the digital
      age.
AB  - Qualitative research is used increasingly in dentistry, due to its potential to
      provide meaningful, in-depth insights into participants' experiences,
      perspectives, beliefs and behaviours. These insights can subsequently help to
      inform developments in dental practice and further related research. The most
      common methods of data collection used in qualitative research are interviews and
      focus groups. While these are primarily conducted face-to-face, the ongoing
      evolution of digital technologies, such as video chat and online forums, has
      further transformed these methods of data collection. This paper therefore
      discusses interviews and focus groups in detail, outlines how they can be used in
      practice, how digital technologies can further inform the data collection
      process, and what these methods can offer dentistry.

PMID- 30287963
TI  - Molar incisor hypomineralisation (MIH) - an overview.
AB  - Recent data indicates that molar-incisor hypomineralisation (MIH) is a frequently
      - encountered dental condition worldwide. The condition could be associated with
      dental complications that might affect patients' quality of life as well as
      create treatment challenges to dentists. The affected teeth are more prone to
      caries and post-eruptive enamel breakdown, therefore, it is believed that this
      condition might be responsible for a substantial proportion of childhood caries
      since the condition has high prevalence. MIH is common, and as such it should be
      diagnosed and managed in primary care wherever possible. Early diagnosis can lead
      to more effective and conservative management. This article aims to highlight
      different aspects related to MIH, from its prevalence to treatment options in
      young patients.

PMID- 30287967
TI  - The ultimate guide to restoration longevity in England and Wales. Part 7:
      premolar teeth: time to next intervention and to extraction of the restored
      tooth.

PMID- 30287966
TI  - A randomised control trial evaluating non-technical skills acquisition using
      simulated situational training in oral surgery.

PMID- 30287968
TI  - A journey through clinical education.
AB  - This opinion piece centres on my own journey through clinical education and
      reflects on my involvement in clinical undergraduate teaching. Utilising
      experiences teaching on undergraduate clinics, before and after attending the
      Advanced Certificate in Clinical Education through the Royal College of Surgeons
      in Glasgow, I address how the course has allowed me to grow and adapt my teaching
      style to provide the optimum learning environment for students. Particular
      emphasis is placed on an andragogical teaching methodology and the importance of
      intrinsic motivation to allow for further clinical development.

PMID- 30287969
TI  - Response To Letter Regarding Article "Long-Term Outcomes in Patients With Type 2
      Myocardial Infarction and Myocardial Injury".

PMID- 30287970
TI  - PCA in High Dimensions: An orientation.
AB  - When the data are high dimensional, widely used multivariate statistical methods
      such as principal component analysis can behave in unexpected ways. In settings
      where the dimension of the observations is comparable to the sample size, upward
      bias in sample eigenvalues and inconsistency of sample eigenvectors are among the
      most notable phenomena that appear. These phenomena, and the limiting behavior of
      the rescaled extreme sample eigenvalues, have recently been investigated in
      detail under the spiked covariance model. The behavior of the bulk of the sample
      eigenvalues under weak distributional assumptions on the observations has been
      described. These results have been exploited to develop new estimation and
      hypothesis testing methods for the population covariance matrix. Furthermore,
      partly in response to these phenomena, alternative classes of estimation
      procedures have been developed by exploiting sparsity of the eigenvectors or the
      covariance matrix. This paper gives an orientation to these areas.

PMID- 30287971
TI  - Choosing a Control Group for Displaced Workers.
AB  - The vast majority of studies on the earnings of displaced workers use a control
      group of never displaced workers to examine the effects of initial displacements.
      This approach attributes earnings declines due to all future job instability to
      the initial displacement event, overstating the losses relative to the average
      treatment effect. This paper's approach isolates the impact of an average
      displacement without conditioning on future displacement status in the control
      group. In comparisons of the standard and alternative approaches using PSID data,
      the estimated long-run earnings losses fall dramatically from 25 percent to as
      low as 5 percent.

PMID- 30287972
TI  - Mothers' Partnerships, Men in the Home, and Adolescents' Secondary Exposure to
      Violence.
AB  - Family instability means that many U.S. youth spend time without biological
      fathers and with other men. This study extends the literature on the
      developmental implications of living with fathers and father figures by
      investigating the association between the presence of mothers' male romantic
      partners in the home and secondary exposure to violence with a focus on
      variability according to the identities of the men and the communities of the
      family. Fixed effects models of multilevel data from the Project on Human
      Development in Chicago Neighborhoods (n = 2,201) revealed that living with
      mothers' partners did not have a general protective or risky association with
      youths' secondary exposure to violence. This exposure, however, was lower when
      such men were youths' biological fathers (vs. social fathers) and when they were
      married to (vs. cohabiting with) youths' mothers. The link between men's marital
      status and exposure to violence appeared stronger in higher-crime neighborhoods.

PMID- 30287973
TI  - Research and Education in Computational Science and Engineering.
AB  - This report presents challenges, opportunities and directions for computational
      science and engineering (CSE) research and education for the next decade. Over
      the past two decades the field of CSE has penetrated both basic and applied
      research in academia, industry, and laboratories to advance discovery, optimize
      systems, support decision-makers, and educate the scientific and engineering
      workforce. Informed by centuries of theory and experiment, CSE performs
      computational experiments to answer questions that neither theory nor experiment
      alone is equipped to answer. CSE provides scientists and engineers with
      algorithmic inventions and software systems that transcend disciplines and
      scales. CSE brings the power of parallelism to bear on troves of data.
      Mathematics-based advanced computing has become a prevalent means of discovery
      and innovation in essentially all areas of science, engineering, technology, and
      society; and the CSE community is at the core of this transformation. However, a
      combination of disruptive developments-including the architectural complexity of
      extreme-scale computing, the data revolution and increased attention to data
      driven discovery, and the specialization required to follow the applications to
      new frontiers-is redefining the scope and reach of the CSE endeavor. With these
      many current and expanding opportunities for the CSE field, there is a growing
      demand for CSE graduates and a need to expand CSE educational offerings. This
      need includes CSE programs at both the undergraduate and graduate levels, as well
      as continuing education and professional development programs, exploiting the
      synergy between computational science and data science. Yet, as institutions
      consider new and evolving educational programs, it is essential to consider the
      broader research challenges and opportunities that provide the context for CSE
      education and workforce development.

PMID- 30287974
TI  - Enantioselective counter-anions in photoredox catalysis: the asymmetric cation
      radical Diels-Alder reaction.
AB  - Control of absolute stereochemistry in radical and ion radical transformations is
      a major challenge in synthetic chemistry. Herein, we report the design of a
      photoredox catalyst system comprised of an oxidizing pyrilium salt bearing a
      chiral N-triflyl phosphoramide anion. This class of chiral organic photoredox
      catalysts is able to catalyze the formation of cation radical-mediated Diels
      Alder transformations in up to 75:25 e.r. in both intramolecular and
      intermolecular examples.

PMID- 30287975
TI  - Copper-Catalyzed Enantioselective Hydroamination of Alkenes.

PMID- 30287977
TI  - Two-Stage Metropolis-Hastings for Tall Data.
AB  - This paper discusses the challenges presented by tall data problems associated
      with Bayesian classification (specifically binary classification) and the
      existing methods to handle them. Current methods include parallelizing the
      likelihood, subsampling, and consensus Monte Carlo. A new method based on the two
      stage Metropolis-Hastings algorithm is also proposed. The purpose of this
      algorithm is to reduce the exact likelihood computational cost in the tall data
      situation. In the first stage, a new proposal is tested by the approximate
      likelihood based model. The full likelihood based posterior computation will be
      conducted only if the proposal passes the first stage screening. Furthermore,
      this method can be adopted into the consensus Monte Carlo framework. The two
      stage method is applied to logistic regression, hierarchical logistic regression,
      and Bayesian multivariate adaptive regression splines.

PMID- 30287976
TI  - Multi-level Supervision and Modification of Artificial Pancreas Control System.
AB  - Artificial pancreas (AP) systems provide automated regulation of blood glucose
      concentration (BGC) for people with type 1 diabetes (T1D). An AP includes three
      components: a continuous glucose monitoring (CGM) sensor, a controller
      calculating insulin infusion rate based on the CGM signal, and a pump delivering
      the insulin amount calculated by the controller to the patient. The performance
      of the AP system depends on successful operation of these three components. Many
      APs use model predictive controllers that rely on models to predict BGC and to
      calculate the optimal insulin infusion rate. The performance of model-based
      controllers depends on the accuracy of the models that is affected by large
      dynamic changes in glucose-insulin metabolism or equipment performance that may
      move the operating conditions away from those used in developing the models and
      designing the control system. Sensor errors and missing signals will cause
      calculation of erroneous insulin infusion rates. And the performance of the
      controller may vary at each sampling step and each period (meal, exercise, and
      sleep), and from day to day. Here we describe a multi-level supervision and
      controller modification (ML-SCM) module is developed to supervise the performance
      of the AP system and retune the controller. It supervises AP performance in 3
      time windows: sample level, period level, and day level. At sample level, an
      online controller performance assessment sub-module will generate controller
      performance indexes to evaluate various components of the AP system and
      conservatively modify the controller. A sensor error detection and signal
      reconciliation module will detect sensor error and reconcile the CGM sensor
      signal at each sample. At period level, the controller performance is evaluated
      with information collected during a certain time period and the controller is
      tuned more aggressively. At the day level, the daily CGM ranges are further
      analyzed to determine the adjustable range of controller parameters used for
      sample level and period level. Thirty subjects in the UVa/Padova metabolic
      simulator were used to evaluate the performance of the ML-SCM module and one
      clinical experiment is used to illustrate its performance in a clinical
      environment. The results indicate that the AP system with an ML-SCM module has a
      safer range of glucose concentration distribution and more appropriate insulin
      infusion rate suggestions than an AP system without the ML-SCM module.

PMID- 30287979
TI  - Predicting secondary school dropout among South African adolescents: A survival
      analysis approach.
AB  - Education is one of the strongest predictors of health worldwide. In South
      Africa, school dropout is a crisis where by Grade 12, only 52% of the age
      appropriate population remain enrolled. Survival analysis was used to identify
      the risk of dropping out of secondary school for male and female adolescents and
      examine the influence of substance use and leisure experience predictors while
      controlling for demographic and known predictors using secondary, longitudinal
      data. Results indicated being male, not living with one's mother, smoking
      cigarettes in the past month, and lower levels of leisure-related intrinsic
      motivation significantly predicted dropout. Results support comprehensive
      prevention programmes that target risk behaviour and leisure.

PMID- 30287978
TI  - Neonatal Micro-RNA Profile Determines Endothelial Function in Offspring of
      Hypertensive Pregnancies.
AB  - Offspring of hypertensive pregnancies are at increased risk of developing
      hypertension in adulthood. In the neonatal period they display endothelial cell
      dysfunction and altered microvascular development. MicroRNAs, as important
      endothelial cellular regulators, may play a role in this early endothelial
      dysfunction. Therefore we identified differential microRNA patterns in
      endothelial cells from offspring of hypertensive pregnancies and determined their
      role in postnatal vascular cell function. Studies were performed on human
      umbilical vein endothelial cell (HUVECs) samples from 57 pregnancies. Unbiased
      RNA-sequencing identified 30 endothelial-related microRNAs differentially
      expressed in HUVECs from hypertensive compared to normotensive pregnancies.
      Quantitative reverse transcription PCR (RT-qPCR) confirmed a significant higher
      expression level of the top candidate, miR-146a. Combined miR-146a targeted gene
      expression and pathway analysis revealed significant alterations in genes
      involved in inflammation, angiogenesis and immune response in the same HUVECs.
      Elevated miR-146a expression level at birth identified cells with reduced ability
      for in vitro vascular tube formation, which was rescued by miR-146a inhibition.
      In contrast, miR-146a overexpression significantly reduced vascular tube
      formation in HUVECs from normotensive pregnancies. Finally, we confirmed that
      mir146a levels at birth predicted in vivo microvascular development during the
      first three postnatal months. Offspring of hypertensive pregnancy have a distinct
      endothelial regulatory microRNA profile at birth, which is related to altered
      endothelial cell behaviour, and predicts patterns of microvascular development
      during the first three months of life. Modification of this microRNA profile in
      vitro can restore impaired vascular cell function.

PMID- 30287980
TI  - Locally optimal designs for some binary dose-response models.
AB  - In this paper, we consider the problem of seeking locally optimal designs for
      nonlinear dose-response models with binary outcomes. Applying the theory of
      Tchebycheff Systems and other algebraic tools, we show that the locally D-, A-,
      and c-optimal designs for three binary dose-response models are minimally
      supported in finite, closed design intervals. The methods to obtain such designs
      are presented along with examples. The efficiencies of these designs are also
      discussed.

PMID- 30287982
TI  - A Discrete-Time Branching Process Model of Yeast Prion Curing Curves.
AB  - The infectious agent of many neurodegenerative disorders is thought to be
      aggregates of prion protein, which are transmitted between cells. Recent work in
      yeast supports this hypothesis, but suggests that only aggregates below a
      critical size are transmitted efficiently. The total number of transmissible
      aggregates in a typical cell is a key determinant of strain infectivity. In a
      discrete-time branching process model of a yeast colony with prions, prion
      aggregates increase in size according to a Poisson process and only aggregates
      below a threshold size are transmitted during cell division. The total number of
      cells with aggregates in a growing population of yeast is expressed.

PMID- 30287983
TI  - Botanical Integrity: The Importance of the Integration of Chemical, Biological,
      and Botanical Analyses, and the Role of DNA Barcoding.
AB  - Raw materials, ingredients, and products derived from plants are commonly
      referred to as herbs or botanicals in both the biomedical literature and the
      natural products health industry. This overarching term includes the breadth of
      crude herbs, plant parts, and the ingredients made from them, and also covers
      finished products such as botanical dietary supplements. Botanical dietary
      supplements are intended to supplement the human diet and are composed primarily
      of powdered plant parts, their extracts, or other preparations derived from crude
      herbal material; some formulations include other ingredients such as vitamins,
      minerals, and amino acids. Botanical dietary supplements are highly complex
      mixtures reflecting the diverse chemical constituents that comprise the source
      plant's raw material. Botanical analysis is an intricate analytical challenge
      requiring specialized skills and instrumentation that is different from those
      required for quality control of chemically simpler pharmaceuticals, or for the
      safety assessment of many conventional food or other products that are generally
      regarded as safe (GRAS).

PMID- 30287981
TI  - Social Problems in ADHD: Is it a Skills Acquisition or Performance Problem?
AB  - Recent models suggest that social skills training's inefficacy for children with
      ADHD may be due to target misspecification, such that their social problems
      reflect inconsistent performance rather than knowledge/skill gaps. No study to
      date, however, has disentangled social skills acquisition from performance
      deficits in children with ADHD. Children ages 8-12 with ADHD (n=47) and without
      ADHD (n=23) were assessed using the well-validated social behavioral analysis
      framework to quantify cross-informant social skills acquisition deficits,
      performance deficits, and strengths. Results provided support for the construct
      and predictive validities of this Social Skills Improvement System (SSIS)
      alternate scoring method, including expected magnitude and valence relations with
      BASC-2 social skills and ADHD symptoms based on both parent and teacher report.
      Acquisition deficits were relatively rare and idiosyncratic for both the ADHD and
      Non-ADHD groups, whereas children with ADHD demonstrated cross-informant social
      performance deficits (d=0.82-0.99) on several specific behaviors involving
      attention to peer directives, emotion regulation, and social reciprocity.
      Relative to themselves, children with ADHD were perceived by parents and teachers
      as exhibiting more social strengths than social acquisition deficits; however,
      they demonstrated significantly fewer social strengths than the Non-ADHD group (d
      = -0.71 to -0.89). These findings are consistent with recent conceptualizations
      suggesting that social problems in ADHD primarily reflect inconsistent
      performance rather than a lack of social knowledge/skills. Implications for
      refining social skills interventions for ADHD are discussed.

PMID- 30287984
TI  - Botanical Integrity: Part 2: Traditional and Modern Analytical Approaches.
AB  - The concept of botanical integrity (BI), introduced previously in HerbalGram
      issue 106, involves the determination of identity, homogeneity, bioactivity, and
      safety of plant-derived materials designated for human consumption.1 It goes
      beyond previously established quality control principles. The inaugural article
      in this series described the three major domains of expertise that are required
      to assess BI (as noted in Figure 1): botanical examination (botany),
      phytochemical analysis (chemistry), and biological efficacy and safety
      assessments (bioactivity, which encompasses the fields of pharmacology and
      toxicology).

PMID- 30287985
TI  - From the Desk of the Editor.

PMID- 30287986
TI  - Rising Incidence of Breast Cancer in the Young Fertile Indian Population-a
      Reality Check.
AB  - Breast cancer in India appears to be diagnosed more in the young women, but
      whether this is an actual higher incidence, and hence a matter of concern, needs
      more clarity, and the extent to which correctable measures can be taken to reduce
      or overcome this additional disease burden, if any, has to be better understood.
      The article analyzes these and more in a systematic manner and highlights the
      important issues in the very young women which makes the clinical management of
      breast cancer more complex.

PMID- 30287987
TI  - Oncologic and Cosmetic Outcomes of Oncoplastic Breast Surgery in Locally Advanced
      Breast Cancer After Neoadjuvant Chemotherapy, Experience from a Developing
      Country.
AB  - Oncoplastic surgery (OPS) has emerged as a new approach for extending breast
      conserving surgery (BCS) possibilities, reducing both mastectomy and re-excision
      rates, while avoiding breast deformities. OPS is based upon the integration of
      plastic surgery techniques for immediate reshaping after wide excision for breast
      cancer. This is a prospective feasibility cohort study of oncoplastic breast
      surgery after neoadjuvant chemotherapy that was carried at the National Cancer
      Institute, Cairo University and included 70 patients. The primary outcome was the
      local recurrence rate. Secondary outcomes included survival and margins obtained
      as well as cosmetic outcomes. Survival analysis was performed. Oncoplastic breast
      surgery did not compromise oncologic safety in the patients included in the
      study. It even allowed wider margins of resection which could be associated with
      better oncologic outcomes. At the same time, it gave a better cosmetic outcome
      and therefore higher patient satisfaction. Oncoplastic breast surgery includes a
      wide spectrum of surgical techniques, ranging from the basic level I techniques
      in breast conserving surgery to the more complex procedures of level II which are
      broadly classified into volume replacement (therapeutic mammoplasty) and volume
      displacement procedures. We suggest that oncoplastic breast surgery techniques
      should be the standard of care in breast surgery. They are the basis for breast
      conserving surgery techniques in early breast cancer. In our experience,
      oncoplastic surgery is feasible in locally advanced tumours after downstaging
      with neoadjuvant chemotherapy without compromising the oncologic safety.

PMID- 30287988
TI  - Role of Plasma D-Dimer Levels in Breast Cancer Patients and Its Correlation with
      Clinical and Histopathological Stage.
AB  - Breast cancer, the most common female malignancy, represents a heterogeneous
      group of tumors, which presen both varied behaviors and response to therapy. This
      study was done with an attempt to evaluate the role of D-dimer in patients of
      carcinoma breast, in predicting lymph node metastasis in carcinoma patients and
      to look for relationship of these markers with histopathologic parameters.
      Clinical data was obtained from clinical examination of patients admitted in the
      Department of Surgery with history of breast lump and confirmed with fine needle
      aspiration cytology (FNAC). Clinical staging was done using TNM staging. D-dimer
      level was measured prior to commencement of treatment, i.e., modified radical
      mastectomy (MRM) or neoadjuvant chemotherapy and finally 6 months after surgery
      or completion of 6 cycles of chemotherapy. The characteristics of the study
      population Out of 60 study cases minimum age of the patient being 30 years and
      maximum being 74 years. Of all histopathologic variables examined, D-dimer levels
      directly correlated with extent of lymph node involvement and lymphovascular
      invasion, D-dimer levels correlated strongest with the number of positive lymph
      nodes, but not with tumor size, estrogen receptor status, and progesterone
      receptor status. This study clearly shows that plasma D-Dimer levels are elevated
      in carcinoma breast patients. Increased D-Dimer levels are an important marker of
      clinical stage, lymphovascular invasion, lymph node involvement, and tumor
      metastasis.

PMID- 30287989
TI  - Quality Indicators for Sentinel Lymph Node Biopsy in Breast Cancer: Applicability
      and Clinical Relevance in a Non-screened Population.
AB  - Quality Indicators for Sentinel Lymph Node Biopsy in Breast Cancer: Applicability
      and Clinical Relevance in a Non-screened Population: sentinel lymph node biopsy
      (SLNB) has replaced axillary lymph node dissection (ALND) as standard of care for
      management of early breast cancer. This study assessed our SLNB program against
      11 published quality indicators (QIs). All breast cancer patients who underwent
      SLNB in our centre from June 2013-Dec 2015 were included. Clinical, pathological
      and follow-up data were extracted from the institutional REDCap data system.
      Analysis was done with SPSS 23. Following validation, 234 patients had SLNB,
      always performed along with primary surgery. Identification rate was 95.3% and >
      1 SLN was identified in 72% of patients. SLNB positivity was 33%, of these, 100%
      underwent ALND. Overall 91% of QI eligible patients underwent SLNB. No ineligible
      patients (T4) underwent SLNB. For the patients who had radio colloid, injection
      criteria were met for 100%. Pathological evaluation and reporting criteria were
      met for 100% of patients. There were no axillary recurrences in a median follow
      up of 2 years. 7.6% patients had SLN negative on frozen section but positive on
      final histology. 7.2% of patients with clinical negative nodes had pN2 disease in
      final histopathology report after surgery. Sixty percent of patients who had
      completion ALND had only positive SLN. This study supports the applicability of
      published QI of SLNB in a non-screened cohort of early breast cancer patients.
      Although QI were useful, modification based on patient characteristics and
      resource availability may be needed. These indicators can be used as audit tools
      to improve the overall accuracy of the procedure.

PMID- 30287990
TI  - Infiltrating Lobular Breast Cancer Presenting as Isolated Gastric Metastasis: a
      Case Report.

PMID- 30287991
TI  - A Survey on Breast Cancer Awareness Among Medical, Paramedical, and General
      Population in North India Using Self-Designed Questionnaire: a Prospective Study.
AB  - Breast cancer (BC) has become the most common cancer in urban women.
      Unfortunately, most women are not aware of BC symptoms/signs, prevention, and
      management. In resource-limited countries like India where we do not have
      structured screening/awareness programs, a majority of women present with locally
      advanced BC. The aim of our study is to identify the present status of awareness
      about BC prevention, early detection, symptoms, and management in urban and rural
      Indian women (medical, paramedical, and nonmedical) and to assess whether
      education and socioeconomic strata have any role in better awareness about BC or
      not. We did a prospective cross-sectional observation study among the medical,
      paramedical, and nonmedical women in the northern part of India. We designed a
      questionnaire keeping in mind the three domains about BC-knowledge (questions 1
      25 include risk factors, genetics, lifestyle changes, hormones, associated
      cancers, and modes of presentation like lump, nipple/skin changes), breast self
      examination (questions 25-37), and attitude to prevention and early detection
      (questions 38-44). We also asked how many do breast self-examination (BSE) and
      what they think are the three main factors responsible for late presentation and
      the three main ways to increase BC awareness. The Likert scale was used for
      objective assessment. We analyzed the whole data using SPSS software version 15.
      A total of 220 women out of 270 completed the questionnaire. Out of 220 women,
      26.4% were medical, 20.9% paramedical, and 52.7% nonmedical. Most women were
      educated (82.7%) and married (65%). 59.5% women resided in urban areas and the
      rest (40.5%) were from rural areas. We found that there was relatively more
      knowledge in the medical group; however, the skills of BSE and attitude to
      prevention and early detection in all the three subgroups and among rural and
      urban women were suboptimal and not different significantly. The three main
      factors responsible for delayed presentation were shyness and not knowing BSE,
      ignorance about BC symptoms, and social stigma of cancer along with financial
      constraints. The three main ways to improve BC awareness suggested were to have
      more advertisements on television and social media, roadside campaigns and in
      colleges along with group discussions and debates, and at grassroots level to
      involve Anganwadi workers and nurses to create more awareness in villages. There
      was less breast cancer knowledge and awareness among the nonmedical women
      compared to those among the medical and paramedical, the skills of BSE and
      attitude to prevention and early detection were suboptimal in all the three
      groups. Rural or urban dwellings did not make much difference in BC knowledge,
      skills of BSE, and attitude to prevention. More awareness regarding breast cancer
      symptoms with early detection and BSE need to be addressed with more information
      dissemination via social media, campaigns, and involvement of paramedics and
      social workers.

PMID- 30287992
TI  - Unusual Breast Neoplasm with Diagnostic and Management Challenges.
AB  - With the growing awareness and availability of proper screening methods,
      detection of breast lump is increasing globally and is now a very sensitive issue
      for females. The treatment of these lumps ranges from lumpectomy to wide local
      excision to mastectomy; hence, a proper diagnosis is very important to prevent
      under- or overtreatment in patients. Breast lesions are the heterogeneous
      diseases encompassing several distinct entities with remarkably different
      characteristics. While the more common forms of breast cancers are well
      recognized and understood better, there are many important unusual lesions and
      malignancies that are less known and less appreciated and can be challenging to
      diagnose. In such cases, due to rarity of the disease and lack of adequate
      treatment protocol, managing the patients can be a challenging task for surgeons
      and oncologist as well. In this article, we have shared our institutional
      experience in unusual breast lesions with emphasis on diagnostic as well as
      management challenges faced.

PMID- 30287993
TI  - Stridor as the First Presentation of Metastatic Breast Cancer that Was Managed
      with Chemotherapy: a Case Report.
AB  - Supraclavicular nodal metastases of breast cancer are rare and occur in about 8%
      of newly diagnosed cases. It is rarely discussed in the literature that breast
      cancer was metastasizing to higher levels of the cervical nodes. We report a case
      of metastatic breast cancer to the deep cervical lymph nodes that caused stridor
      due to compression of the recurrent laryngeal nerve which was diagnosed by
      indirect laryngoscopy. After full investigations, urgent chemotherapy was started
      and it showed a dramatic response with disappearance of the lymph node after two
      cycles with resolution of the stridor. This report also highlights the
      association of other metastatic sites with this higher level of neck nodal
      metastases of breast cancer.

PMID- 30287994
TI  - Rare Case Report of Neuroendocrine Tumor in Axilla-Metastasis from Unknown
      Primary or De Novo?
AB  - Neuroendocrine tumors (NET) are the neoplasm arising from neuroendocrine cells
      which are present throughout the body. It can be benign, being more common or
      malignant. Gut is the most common site, but they can be seen in any part of the
      body. We had a case of grade III NET in axilla presented with a fungating lesion
      with unknown primary. Clinical behavior of such tumor is predicted by tumor grade
      or differentiation. We treated this patient by surgery and adjuvant chemotherapy.

PMID- 30287995
TI  - Nipple Areola Complex Involvement in Invasive Carcinoma Breast.
AB  - A variety of factors including tumor biology and distance of the tumor from the
      nipple have been associated with nipple areola complex involvement in patients
      with breast cancer. Preoperative understanding regarding these factors can help
      in modifying the surgical options including preservation of nipple areola complex
      (NAC) and breast conservation. Nipple sparing surgery (breast conservation
      surgery/skin sparing mastectomy with immediate reconstruction) for breast cancer
      has gained widespread interest with the aim of achieving oncologically safe and
      cosmetically acceptable outcome. To study the proportion of cases with nipple
      areola complex involvement in invasive carcinoma breast and to describe the
      variables predictive of nipple areola complex involvement in patients undergoing
      excision of tumor along with NAC for invasive carcinoma breast. A cross-sectional
      study was conducted among 136 patients who underwent mastectomy in Regional
      Cancer Center, Thiruvananthapuram. Tumor nipple distance was assessed
      preoperatively using mammogram and postoperatively by histopathological
      examination. Nipple involvement was seen only among 4.4%. Preoperative assessment
      of tumor to nipple distance, tumor size, location, and stage of the disease
      agrees with the histopathological examination. Only a small proportion of breast
      cancer has NAC involvement and preoperative assessment could help the surgeon in
      deciding on the feasibility of NAC preservation.

PMID- 30287996
TI  - Bilateral Breast and Axillary Lymph Nodes Metastases of an Ovarian Serous
      Cystadenocarcinoma.

PMID- 30287997
TI  - Dermatofibrosarcoma Protuberans of the Breast-a Rare Entity.
AB  - Dermatofibrosarcoma protuberans (DFSP) represents about 1% of soft-tissue
      sarcomas with an estimated incidence of 0.8 to 5.0 cases per million per year.
      This lesion may occur anywhere in the body but more than 50% occur on the trunk,
      20% on the head and neck and 30% on the extremities. DFSP of the breast is an
      extremely uncommon site of presentation. Data regarding DFSP of the breast is
      limited and mostly in the form of case reports. Clinical presentation is not
      uniform and may mimic benign skin lesions [1]. However, it typically presents as
      a nodular cutaneous mass in early or mid-adult life. We herein report a case of
      DFSP of the breast in a 33-year-old lady who was managed successfully in our
      institute and review the literature associated with it.

PMID- 30287998
TI  - Identification of Sentinel Lymph Nodes Using Contrast-Enhanced Ultrasound in
      Breast Cancer.
AB  - Sentinel lymph node (SLN) biopsy has become the standard of care in axillary
      staging of breast cancer patients who are clinically node negative as it reduces
      the morbidity of axillary nodal dissection. SLN biopsy using blue dye and
      radioisotopes have high identification rates but its limitations include
      anaphylaxis, disposal of radioactive waste, and potential second surgery in up to
      35% of patients who show nodal metastases on SLN biopsy. Contrast-enhanced
      ultrasound (CEUS) has the potential for SLNs to be identified without the
      aforementioned risks. CEUS involves the administration of intravenous contrast
      agents containing microbubbles of perfluorocarbon or nitrogen gas. The bubbles
      greatly affect ultrasound backscatter and increase vascular contrast in a similar
      manner to intravenous contrast agents used in CT and MRI. It is safe and easily
      performed with no requirement for ionizing radiation and no risk of
      nephrotoxicity. Microbubbles are taken up by lymph nodes when injected directly
      into tissues, including sub-areolar injection in the breast cancer patient. This
      method may prove valuable in patients with ductal carcinoma in situ, where
      operative SLN biopsy remains controversial, and in women undergoing prophylactic
      mastectomies for high risk. This technique may also have a role after neoadjuvant
      chemotherapy where frequently there is fibrosis in the treated SLNs.

PMID- 30287999
TI  - Reconstruction in Breast Conservation Therapy-Single Tertiary Care Institution
      Experience with 472 Patients.
AB  - Breast conservation therapy (BCT) is now internationally accepted treatment for
      early breast cancer. Despite of high incidence of carcinoma breast in India, BCT
      rates are very low as compared to the west. In this article, we wish to share our
      experience of breast conservation with oncoplasty in Indian women. A
      retrospective analysis of case records of patients treated with oncoplastic
      breast conservation from January 2009 to June 2014 in a single surgical oncology
      unit in a tertiary cancer institute. Demographic patient data, stage of disease,
      location of primary tumour, use of neo-adjuvant chemotherapy if received, tumour
      size and breast size ratio, reconstruction method used, post-operative
      complications and aesthetic score of patients were analysed. Various methods of
      oncoplasty and partial breast reconstruction used are discussed. Four hundred and
      seventy-two patient records were found suitable for analysis. Most common stage
      of presentation was T2N0 in 189 patients (40%). Forty-one patients received neo
      adjuvant chemotherapy (NACT). Tumour arising in upper outer quadrant was most
      common site, seen in 268 (56.7%). The most common method of reconstruction was
      volume displacement, done in 57.6% patients. Overall surgical complications
      included wound infection with or without dehiscence, seroma formation, partial
      flap necrosis and fat necrosis. Cosmesis was found to be excellent in 23.09% and
      good in 58.47% at 6-month follow-up. Breast conservation with oncoplasty is
      oncologically safe for early breast cancer treatment and has good cosmetic
      outcome with high patient satisfaction rates. Its practice should be encouraged
      in Indian set-up also.

PMID- 30288000
TI  - Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) for Prevention of
      Breast Cancer-Related Lymphedema-a Preliminary Report.
AB  - Lymphatic microsurgical preventing healing approach (LYMPHA) for prevention of
      breast cancer-related lymphedema (BCRL)-a preliminary report BCRL-is a chronic
      debilitating condition which impairs quality of life of breast cancer survivors.
      The aim is to study the feasibility of preventing lymphedema by performing
      "Lymphatic Microsurgical Preventive Healing Approach (LYMPHA)." Patients
      undergoing breast cancer surgery with complete nodal dissection were taken up for
      the study. After the standard axillary nodal dissection, lymphatics were
      identified by the help of blue dye and were anastomosed with a tributary to the
      axillary vein. Post-operatively, patients were followed up clinically for
      development of lymphedema and lymphoscintigraphy was performed after treatment
      completion. A total of 35 patients were enrolled for the study. The average BMI
      was 29.5. LYMPHA was feasible in all cases. The number of lymphatics identified
      was 1 to 5 per axilla. Two patients developed transient lymphedema which resolved
      with conservative therapy and patients were able to discontinue the compression
      garment. Follow-up lymphoscintigraphy is performed in two patients, which showed
      normal lymphatic flow. LYMPHA is a feasible technique, not difficult to perform,
      takes a short time, is accomplished in same general anesthesia as for axillary
      dissection, and gives no extra scar. The early results are promising and long
      term follow-up may make the procedure as a routine.

PMID- 30288001
TI  - Patterns of Care of Breast Cancer Patients in a Rural Cancer Center in Western
      India.
AB  - Breast cancer is an emerging public health problem in low- and middle-income
      countries. The main objective is to describe the clinical characteristics and
      patterns of care of breast cancer patients diagnosed and treated in a rural
      cancer hospital in Barshi, Western India. The results from a cross-sectional
      study of 99 consecutive breast cancer patients diagnosed and treated between
      February 2012 and November 2014 in Nargis Dutt Memorial Cancer Hospital is
      reported. The case records of the patients were scrutinized and reviewed to
      abstract data on their clinical characteristics, diagnostic, and treatment
      details. The mean age at diagnosis of the patients was 52.8 +/- 11.6 years; 83.5%
      of women were married, and 60.6% were illiterate. Sixty percent of patients had
      tumors measuring 5 cm or less. Almost half of the patients (46.4%) had stage I or
      II A disease and a third (36.0%) had axillary lymph node metastasis. Estrogen,
      progesterone, and human epidermal growth factor receptor2 receptor status were
      investigated in 41 (41.4%) of patients only. The median interval between
      diagnosis and initiation of treatment was 11 days. Modified radical mastectomy
      was done in 91% of patients, and nearly a third of patients who were prescribed
      chemotherapy did not complete treatment. The rural-based tertiary cancer care
      center has made treatment more accessible to breast cancer patients and has
      reduced the interval between diagnosis and treatment initiation. However, there
      are still many challenges like non-compliance to and incomplete treatments and
      poor follow-up that need to be addressed.

PMID- 30288003
TI  - Malignant Spindle Cell Tumor Breast-a Diagnostic Dilemma.
AB  - Primary malignant spindle cell tumors are rare constituting 1.0% of breast
      malignancies. Spindle cell lesions occurring in soft tissues can occur in breast
      with overlapping morphologies. It can present as benign lesion and have
      inconclusive cytological findings, so easily missed if not properly dealt with.
      Stromal sarcoma should be diagnosed only after thorough sectioning and negative
      staining for p63, broad spectrum, and high molecular weight keratin. We present a
      case of right breast lump. Cytological features revealed fibro histiocytic
      lesion. There were no areas of necrosis, hemorrhage, or calcification.
      Histopathologically, it showed partially encapsulated tumor with cells arranged
      in sheets, composed of oval to epithelioid cells with spindling at places with
      moderate pleomorphism (mitotic activity 6-7/10 hpf). Differential diagnosis of
      primary stromal sarcoma, metaplastic sarcoma, and phyllodes was made.
      Immunohistochemistry revealed vimentin positivity with focal positivity of S-100.
      Desmin, cytokeratin and smooth muscle actin, p63, ER, PR, and Her2-neu were
      negative. A final diagnosis of primary breast sarcoma of neural origin was
      established with the help of histopathology and immunohistochemistry. To
      conclude, it is of utmost importance to identify primary stromal sarcomas as they
      are known to spread very rapidly and have a poor prognosis.

PMID- 30288002
TI  - Clinico-pathological Features of PIK3CA Mutation in HER2-Positive Breast Cancer
      of Indian Population.
AB  - PIK3CA pathway is one of the important signaling pathways in cells, which is
      involved in cell proliferation, cell survival, motility, and growth. Mutation in
      PIK3CA gene negatively effects to anti-HER2 therapy in breast cancer patients.
      PIK3CA gene of HER2-positive breast cancers associated with reduced sensitivity
      to neoadjuvant therapy. In this study, we assessed the frequency of PIK3CA
      mutations and influence of PIK3CA mutations on patient survival in a series of
      HER2-positive breast cancer patients. PIK3CA mutations were assessed by
      pyrosequencing and next generation sequencing in 107 HER2-positive breast cancer
      patients of a tertiary Cancer Centre of India from Jan 2012 to Jun 2013 with
      minimum follow-up of 3 years. We found PIK3CA mutations in 26 tumors (24.2%) of
      which 5 were in exon 9, 20 were in exon 20, and 1 was in both exon 9 and 20. In
      exon 9, the mutation c.1634A>G was found in 4 cases and mutation c.1636C>A was
      found in 2 cases. In exon 20, the mutation c.3140A>G was found in 15 cases and
      c.3140A>T was found in 6 cases. The outcome between PIK3CA mutated versus PIK3CA
      wild type was significant showing p value 0.014. Overall survival of mutation and
      treatment with herceptin, mutation with other chemotherapy treatment in both
      early breast cancer (EBC), and locally advanced breast cancer (LABC) showed
      significant p value 0.037 and 0.044 respectively. In conclusion, we identified
      24.2% somatic mutation of PIK3CA in HER2-positive breast cancer patients. PIK3CA
      mutation is significantly associated with ER-positive tumors. The frequency and
      distribution pattern reported in this study is similar to the global report.
      Overall survival of PIK3CA mutation is slightly lower but in patients who
      received herceptin with PIK3CA mutation showed better clinical outcome.

PMID- 30288004
TI  - Numb Chin Syndrome as the Initial Manifestation of Breast Carcinoma.
AB  - Numb chin syndrome may be the manifestation of a local dental pathology or
      secondary to a systemic disease. A systematic physical examination with
      diagnostic workup is of utmost importance in patients presenting with numb chin
      syndrome. We report the case of a 58-year-old woman who presented with numb chin
      syndrome. An orthopantogram and computed tomography of the head revealed
      osteolytic lesion in the left molar region. Histopathological and
      immunohistochemical examination confirmed the lesion to be metastatic breast
      carcinoma. Breast ultrasound scan demonstrated a 1.5 * 1.5-cm lesion in the left
      breast and fine needle aspiration cytology from the lesion confirmed the
      diagnosis of breast carcinoma. Bone scan showed multiple bone metastases. She was
      diagnosed to have numb chin syndrome secondary to bone metastases from breast
      carcinoma. In view of her disseminated disease status, she was started on
      palliative hormone therapy (Letrozole) with zoledronic acid. We present this case
      to highlight the importance of careful evaluation of patients presenting with
      numb chin syndrome because this may be the only manifestation of a systemic
      malignancy.

PMID- 30288005
TI  - Extensive Re-ossification and Reformation of the Proximal Femur After External
      Beam Radiotherapy in Metastatic Carcinoma Breast.
AB  - Management of metastatic bone disease is still evolving and is dependent upon
      many factors including the primary tumour type, expected life expectancy, site
      and size of lesion, character of the lesion, lytic or blastic, and the number of
      lesions. Active orthopaedic surgical intervention is usually required at the time
      of pathological fracture either impending or actual. Management options are
      either in situ fixation or replacement/arthroplasty. The role of post-operative
      radiotherapy is still not clearly defined and its biological effect on healing of
      pathological fracture is unclear. In this report, we describe a case of breast
      carcinoma with a large metastatic lytic lesion in the proximal femur, which was
      treated by in situ fixation followed by hormonal therapy and external beam
      radiotherapy. In the post-operative period, rapid and dramatic ossification and
      reformation of the proximal femur was observed.

PMID- 30288006
TI  - Carcinosarcoma of Breast Mimicking Breast Abscess.
AB  - Carcinosarcoma, a tumor having both carcinomatous and sarcomatous elements,
      occurring in the breast, is a rare condition. The tumor consists of both
      epithelial and mesenchymal cell lines and tends to behave aggressively. It has
      clinical features like that of invasive breast carcinoma but sometimes there can
      be diagnostic confusion as it can mimic or present as breast abscess. Treatment
      is multimodal. Surgery plays the vital role. Post-op radiation and chemo are
      indicated. Hormone therapy is usually inapplicable as most of the time, it is
      hormone receptor negative.

PMID- 30288007
TI  - A Prospective Observational Study of Breast Lumps in Adolescent Girls: Tertiary
      Care South Indian Teaching Hospital Experience.
AB  - The aim of the current study was to assess the incidence and varying clinical
      presentations of benign breast lumps in adolescent age group in a Tertiary care
      Medical College Hospital. This was a prospective, observational study of 6-year
      duration (2011 to 2017) conducted in a Medical College, South India. All
      adolescent age group patients visiting the outpatient department (OPD) with
      complaints of breast lump were enrolled into the study. Triple assessment
      comprising of clinical examination, imaging, and core biopsy was used for
      diagnosis and identification of type of tumor. Management of tumors was based on
      pathology of core biopsy. During the study duration (2011 to 2017), a total of 15
      pediatric patients of age between 11 to 14 years, presented with complaints of
      breast lumps. The most common symptom included painless lump in breast in 11
      patients (73.34%). The histopathological examination (HPE) reported 12 cases
      (80%) as fibroadenomas and only 3 cases (20%) were phyllodes tumors. Based on the
      results of HPE, majority of the patients (53.34%) underwent circumareolar
      cosmetic incision. The most common lesions in pediatric age group are benign
      fibroadenomas; however, phyllodes are also not rare, and to manage them
      appropriately, they should be diagnosed preoperatively with core biopsy. Cases of
      malignancy, including phyllodes tumors, ductal adenocarcinomas, and metastatic
      lesions, have been documented in children and adolescents. Therefore, malignancy
      should be considered in the diagnosis of a pediatric and adolescent breast mass
      until formally ruled out.

PMID- 30288008
TI  - Prospective Evaluation of Surgical Outcome After Transoral CO2 Laser Resection of
      Potentially Malignant and Early Oral Malignancy.
AB  - A prospective observational study was done at the Regional Cancer Centre,
      Thiruvananthapuram, a tertiary referral center for cancer care in India with an
      aim to assess the surgical outcomes of CO2 laser resection of oral lesions in
      terms of operative time, blood loss, hospital stay, postoperative pain, time to
      re-epithelization, pathological margins achieved and the postoperative scar. The
      excision was performed in 30 patients with a diagnosis of either potentially
      malignant lesions (leucoplakia, erythroplakia) or early cancers, i.e., carcinoma
      in situ or T1/T2 squamous cell carcinoma of the anterior oral cavity (tongue,
      buccal mucosa), adhering to standard oncological principles, and the resultant
      defect was left for secondary healing.

PMID- 30288010
TI  - Encapsulated Follicular Variant of Papillary Thyroid Carcinoma Arising in a
      Follicular Adenoma: a Diagnostic Dilemma.
AB  - Papillary thyroid carcinoma (PTC) arising within follicular adenoma is a rare
      histological subset of papillary carcinoma. A 24-year-old female (euthyroid and
      asymptomatic) presented with a solitary mass in the right lobe of thyroid for 2
      years. Fine-needle aspiration cytology (FNAC) suggested features of hyperplasia
      of thyroid. Hemithyroidectomy was performed. Histopathological examination
      revealed two distinct areas and was reported as encapsulated variant of papillary
      carcinoma along with follicular adenoma. Papillary carcinoma was confirmed by
      positive immunohistochemistry for HBME-1. CT head and neck region ruled out
      metastasis and the patient was kept on follow-up. There have been reports of
      medullary and papillary carcinomas occurring together; however, there is a
      paucity of literature on co-existing follicular neoplasm and papillary carcinoma.
      We hereby report a rare case of follicular variant of papillary carcinoma arising
      within follicular adenoma of the thyroid.

PMID- 30288009
TI  - Acute Trauma Precipitating the Onset of Chest Wall Myxofibrosarcoma.
AB  - A previously healthy, 47-year-old male presented to his primary care physician
      with the complaint of a nontender, palpable breast mass discovered coincidentally
      1 month after being scratched in the same location by his pet cat. Family history
      revealed his father was diagnosed with a soft tissue sarcoma of the thigh, 6
      months following a traumatic injury in the same location. Cat scratch disease was
      considered; however, Bartonella Henselae antibody testing was negative. Imaging
      studies revealed a subpectoral mass without rib involvement. Subsequent core
      biopsy revealed malignant fibrous histiocytoma, myxoid type, also known as
      myxofibrosarcoma. The patient underwent complete surgical resection with no
      complications. Medical advice recommended adjuvant radiation therapy due to the
      high risk of recurrence; however, the patient refused this option. Twenty-five
      months later, the patient remains in remission and in overall good health. This
      case describes the development of a chest wall tumor, diagnosed as
      myxofibrosarcoma, following acute trauma to the area. The association between
      acute traumatic injury and the development of a soft tissue sarcoma, as described
      in this case, continues to be widely reported, suggesting the possibility for an
      underlying causal mechanism. Future studies are required to unravel the
      pathogenesis in order to advance the management of this disease.

PMID- 30288011
TI  - Current Status of Lymphadenectomy During Radical Nephroureterectomy for Upper
      Tract Urothelial Cancer-Yes, No or Maybe?
AB  - While pelvic lymphadenectomy during radical cystectomy for bladder cancer is a
      well-established standard of care, the same does not hold true for upper tract
      urothelial carcinoma (UTUC). Indeed, a template-based lymphadenectomy is rarely,
      if ever, performed in conjunction with radical nephroureterectomy at most centres
      across the globe. While multiple studies have explored the staging and
      therapeutic role of lymphadenectomy in cases of UTUC, there remain large gaps in
      our understanding of the indications, extent and safety of this procedure as an
      adjunct to nephroureterectomy. This article elucidates the current knowledge on
      outcomes, benefits and complications of template-based lymphadenectomy during
      radical nephroureterectomy for UTUC. We also explore the current evidence-based
      guidelines on this controversial topic.

PMID- 30288012
TI  - Resection of Isolated Port Site Metastasis in Gall Bladder Cancers-Careful
      Selection and Perioperative Systemic Therapy May Improve Outcomes.
AB  - Excision of port site (PSE) for patients having undergone laparoscopic
      cholecystectomy (LC) is not a standard recommendation. We retrospectively
      evaluated a cohort of patients with isolated PSM without any prior cancer
      directed therapy who were assessed for resection between March 2012 and July 2016
      at Tata Memorial Hospital, Mumbai. Eleven of a total 13 patients underwent wide
      excision for PSM in the given time period. Upfront resection was undertaken in
      six patients while seven patients received neoadjuvant chemotherapy (NACT) and
      two received neoadjuvant chemo radiotherapy (NACTRT) prior to attempted
      resection. With the median follow-up of 22 months, post PSM disease-free survival
      (DFS) was 20 months (95% CI 15-24 months) and overall survival (OS) was 37 months
      (95% CI 22-51 months). Careful selection along with an aggressive management
      strategy may be a step forward in the treatment of patients with isolated PSM.

PMID- 30288013
TI  - Ovarian Transposition in a Young Girl with Primitive Neuroectodermal Tumor of
      Bladder.

PMID- 30288014
TI  - Giant Calcified Retroperitoneal Teratoma.
AB  - Retroperitoneal teratoma involving adrenal gland is a rare entity in adults
      comprising only 4% of all primary teratomas. These tumors are mainly seen in
      infants and children. Diagnosis is made by X-ray and CT abdomen showing the
      presence of large tumor with cystic and calcified walls. Here, we present an
      interesting image of a 16-year-old girl who presented with large (12 * 10 cm)
      calcified cyst occupying left side of abdomen which was treated successfully by
      surgical excision.

PMID- 30288015
TI  - Agronomic biofortification of cereal crop plants with Fe, Zn, and Se, by the
      utilization of coal fly ash as plant growth media.
AB  - The implementation of agronomic biofortification of cereal crops with Fe, Zn, and
      Se appears to be a rapid and simple solution to the deficiency of these elements
      in soils and plants. These deficiencies are a reason for serious public health
      concerns. Low levels of Fe, Zn, and Se are important soil constraints to crop
      production, especially in the developing world. In our study we planted six
      cereal crops on soil control and different coal combustion residues, naturally
      rich in these micronutrients. Plants were harvested and chemically analyzed for
      Fe, Zn, and Se concentration using ICP. Six plant species have been tested
      including barley (Hordeum vulgare), Jerry oats (Avena sativa), rye (Secale
      cereale), wheat (Triticum aestivum), perennial ryegrass (Lolium multiflorum), and
      ReGreen (wheat x wheatgrass hybrid (Triticum aestivum x Thinopyrum intermedium).
      All tested plants were able to establish growth on coal ash based growth media,
      and accumulated significant amounts of Fe, Zn, and Se. It supported our
      hypothesis, that phytoremediation of coal ash piles may serve also as agronomic
      biofortification of plants, especially cereal crops cultivated on coal fly ash
      (FA).

PMID- 30288016
TI  - Mechanism and Catalysis of Oxidative Degradation of Fiber-Reinforced Epoxy
      Composites.
AB  - Carbon fiber-reinforced polymer (CFRP) materials are widely used in aerospace and
      recreational equipment, but there is no efficient procedure for their end-of-life
      recycling. Ongoing work in the chemistry and engineering communities emphasizes
      recovering carbon fibers from such waste streams by dissolving or destroying the
      polymer binding. By contrast, our goal is to depolymerize amine-cured epoxy CFRP
      composites catalytically, thus enabling not only isolation of high-value carbon
      fibers, but simultaneously opening an approach to recovery of small molecule
      monomers that can be used to regenerate precursors to new composite resin. To do
      so will require understanding of the molecular mechanism(s) of such degradation
      sequences. Prior work has shown the utility of hydrogen peroxide as a reagent to
      affect epoxy matrix decomposition [1]. Herein we describe the chemical
      transformations involved in that sequence: the reaction proceeds by oxygen atom
      transfer to the polymer's linking aniline group, forming an N-oxide intermediate.
      The polymer is then cleaved by an elimination and hydrolysis sequence. We find
      that elimination is the slower step. Scandium trichloride is an efficient
      catalyst for this step, reducing reaction time in homogeneous model systems and
      neat cured matrix blocks. The conditions can be applied to composed composite
      materials, from which pristine carbon fibers can be recovered.

PMID- 30288017
TI  - A 15-channel 30-V Neural Stimulator for Spinal Cord Repair.
AB  - This paper presents a 15-channel, 30-V, implantable current stimulator for
      restoring locomotion control after spinal cord injuries. The stimulator features
      performance specifications comparable to those of large desktop instrumentation:
      high linearity, high precision of the delivered currents, small channel-to
      channel mismatches and a fast settling time of 0.3 MUs. An ADC-based active
      charge balancing scheme using a digital PI (proportional-integral) controller was
      implemented in firmware.

PMID- 30288018
TI  - Murrangatin suppresses angiogenesis induced by tumor cell-derived media and
      inhibits AKT activation in zebrafish and endothelial cells.
AB  - Introduction: Lung cancer is a major cancer type and a leading cause of cancer
      related death. Angiogenesis plays a crucial role in lung cancer pathogenesis and
      its inhibition is beneficial to patients. Materials and methods: Murrangatin, a
      natural product, can inhibit the proliferation of lung cancer cells, so herein we
      investigated its anti-angiogenic effects in transgenic zebrafish TG (fli1: EGFP)
      and in lung cancer cell-induced angiogenesis in human umbilical vein endothelial
      cells. Results: We found that murrangatin strongly inhibited the growth of
      subintestinal vessels in zebrafish embryos and tumor conditioned media-induced
      angiogenic phenotypes including cell proliferation, cell invasion, cell
      migration, and tube formation. Additionally, murrangatin greatly attenuated
      conditioned medium-induced AKT phosphorylation, but not extracellular signal
      regulated kinase 1/2 phosphorylation. Discussion and conclusion: These findings
      indicate that murrangatin can inhibit tumor-induced angiogensis, at least in part
      through the regulation of AKT signaling pathways. Murrangatin may, therefore, be
      a potential candidate for the development of new anti-lung-cancer drugs.

PMID- 30288021
TI  - Intravenous tranexamic acid use in revision total joint arthroplasty: a meta
      analysis.
AB  - Purpose: Massive perioperative blood loss in complex revision total joint
      arthroplasty (TJA) often requires blood transfusions. Tranexamic acid (TXA) has
      been used in elective primary TJA to minimize blood loss and transfusions. The
      purpose of this meta-analysis was to evaluate the safety and efficacy of
      intravenous TXA in revision TJA. Methods: A literature search of PubMed, Scopus,
      and the Cochrane Controlled Trials Register was performed to identify studies
      published between January 2000 and May 2017. All randomized controlled trials
      (RCTs) and retrospective cohort observational studies evaluating the efficacy of
      intravenous TXA during revision total knee arthroplasty (TKA) and total hip
      arthroplasty (THA) were included. The mean differences (MDs) of blood loss,
      hemoglobin (Hb) change, and red blood cell (RBC) units transfused were compiled,
      and ORs of transfusion and venous thromboembolism (VTE) events in TXA and control
      groups were calculated. Results: Seven studies involving 930 patients were
      included (501 TXA vs 429 control). Intravenous TXA use had a significantly less
      blood transfusion (OR=0.20, 95% CI=0.11-0.34, P<0.001), lower Hb drop (MD=-0.88,
      95% CI=-1.31 to -0.44, P<0.001), and less number of RBC units transfused (MD=
      0.44, 95% CI=-0.65 to -0.24, P<0.001) compared to control in the postoperative
      period. No significant difference was seen in blood loss (MD=-245, 95% CI=-556 to
      66, P=0.12) and VTE events (OR=0.57, 95% CI=0.13-2.42, P=0.45) between groups.
      Conclusion: Our meta-analysis suggests that intravenous administration of TXA can
      significantly reduce blood transfusion requirements following revision TJA,
      without increasing the risk of VTE. However, due to the variation in included
      studies, larger RCTs are required to draw firm conclusions.

PMID- 30288020
TI  - Profile of asfotase alfa in the treatment of hypophosphatasia: design,
      development, and place in therapy.
AB  - Hypophosphatasia (HPP) is a multi-systemic metabolic disorder caused by loss-of
      function mutations in the ALPL gene that encodes the mineralization-associated
      enzyme, tissue-nonspecific alkaline phosphatase (TNSALP). HPP is characterized by
      defective bone and dental mineralization, leading to skeletal abnormalities with
      complications resulting in significant morbidity and mortality. Management of HPP
      has been limited to supportive care until the introduction of a recently approved
      enzyme replacement therapy employing bone-targeted recombinant human TNSALP,
      asfotase alfa (AA). This new therapy has been transformative as it improves
      survival in severely affected infants, and overall quality of life in children
      and adults with HPP. This review provides an overview of HPP, focusing on
      important steps in the development of AA enzyme replacement therapy, including
      the drug design, preclinical studies in the HPP mouse model, and outcomes from
      clinical trials and case report publications to date, with special attention
      given to response to therapy of skeletal manifestations, biochemical features,
      and other clinical manifestations. The limitations, adverse effects, and outcomes
      of AA are outlined and the place in therapy for individuals with HPP is
      discussed.

PMID- 30288022
TI  - Colorectal cancer combination therapy using drug and gene co-delivered, targeted
      poly(ethylene glycol)-epsilon-poly(caprolactone) nanocarriers.
AB  - Purpose: Combination therapy is a promising strategy to treat cancer due to the
      synergistic effects. The drug and gene co-delivered systems attract more
      attention in the field of combination therapy. Materials and methods: In the
      present research, poly(ethylene glycol)-epsilon-poly(caprolactone) block
      copolymer was used for the co-loading of 5-fluorouracil (5-FU) and gene. The
      physicochemical characteristics, in vitro and in vivo anticancer, and gene
      transfection efficiency were tested on colon cancer cells and tumor-bearing mice.
      Results: 5-FU and gene co-loaded nanocarriers had a size of 145 nm. In vivo gene
      delivery results showed about 60% of gene-positive cells. Tumor volume of
      nanocarrier groups at day 21 was around 320 mm3, which is significantly smaller
      compared with free 5-FU group (852 mm3) and control group (1,059 mm3). The
      maximum 5-FU plasma concentration in nanocarrier groups (49 ug/mL) was
      significantly greater than free 5-FU (13 ug/mL). At 24 hours, drug level of
      nanocarrier groups was about 2.8 ug/mL compared with 0.02 ug/mL of free 5-FU.
      Conclusion: The resulting nanocarriers co-loaded with the anticancer drugs and
      genes could be considered as a promising nanomedicine for colorectal cancer
      therapy.

PMID- 30288024
TI  - Synergistic combination therapy of lung cancer using paclitaxel- and triptolide
      coloaded lipid-polymer hybrid nanoparticles.
AB  - Purpose: Non-small cell lung cancer (NSCLC) accounts for the majority of lung
      cancer. Lipid-polymer hybrid nanoparticles (LPNs) combine the advantages of both
      polymeric nanoparticles and liposomes into a single delivery platform. In this
      study, we engineered LPNs as the co-delivery system of paclitaxel (PTX) and
      triptolide (TL) to achieve synergistic therapeutic effect and reduced drug
      resistance. Materials and methods: In this study, PTX- and TL-coloaded LPNs (P/T
      LPNs) were fabricated by nanoprecipitation method using lipid and polymeric
      materials. The P/T-LPNs combination effects on human lung cancer cells were
      studied. Therapeutic potentials of P/T-LPNs were further determined using lung
      cancer cells-bearing mice model. Results: The average particle sizes of LPNs were
      around 160 nm, with narrow size distribution below 0.2. The zeta potential value
      of LPNs was about -30 mV. The encapsulating efficiency (EE) of PTX and TL loaded
      in LPNs was over 85%. The cytotoxicity of dual drug loaded LPNs was higher than
      single drug loaded LPNs. The combination therapy showed synergistic when PTX:TL
      weight ratio was 5:3, indicating the synergy effects of the LPNs. In vivo tumor
      growth curve of the experimental group was more gentle opposed to the control
      group, and tumor volumes of P/T-LPNs and control group were 392 and 1,737 mm3,
      respectively. The inhibition rate on day 20 was 77.4% in the P/T-LPNs group,
      which is higher than the free drugs solution. Conclusion: The in vivo and in
      vitro results proved the synergetic effect of the two drugs coloaded in LPNs on
      the lung cancer xenografts, with the least systemic toxic side effect.

PMID- 30288019
TI  - Current development of biodegradable polymeric materials for biomedical
      applications.
AB  - In the last half-century, the development of biodegradable polymeric materials
      for biomedical applications has advanced significantly. Biodegradable polymeric
      materials are favored in the development of therapeutic devices, including
      temporary implants and three-dimensional scaffolds for tissue engineering.
      Further advancements have occurred in the utilization of biodegradable polymeric
      materials for pharmacological applications such as delivery vehicles for
      controlled/sustained drug release. These applications require particular
      physicochemical, biological, and degradation properties of the materials to
      deliver effective therapy. As a result, a wide range of natural or synthetic
      polymers able to undergo hydrolytic or enzymatic degradation is being studied for
      biomedical applications. This review outlines the current development of
      biodegradable natural and synthetic polymeric materials for various biomedical
      applications, including tissue engineering, temporary implants, wound healing,
      and drug delivery.

PMID- 30288025
TI  - Lycium barbarum polysaccharide prevents cisplatin-induced MLTC-1 cell apoptosis
      and autophagy via regulating endoplasmic reticulum stress pathway.
AB  - Background: Lycium barbarum polysaccharide (LBP) has been reported to contribute
      to the recovery of male hypogonadism and infertility. Aim: The aim of current
      study was to investigate the underlying mechanisms of LBP on male infertility
      recovery. Methods: Recently, it is reported that cell apoptosis mediated by
      endoplasmic reticulum stress (ERS) was distinguished from that mediated by death
      reporters and mitochondria pathway, which could induce cell apoptosis
      independently. The possible signaling mechanisms were investigated using
      diversified molecular biology techniques, such as flow cytometry, western
      blotting, and immunofluorescence. Results: In this study, we found that LBP
      protected Leydig MLTC-1 cells against cisplatin (DDP) by regulating ERS-mediated
      signal pathway, which was evidenced by downregulation of phosphorylation PERK,
      phosphorylation of eukaryotic translation-initiation factor 2alpha and activating
      transcription factor 4. Meanwhile, LBP decreased DDP-induced MLTC-1 cell
      apoptosis via reducing ERS apoptosis-relative proteins caspase 3, caspase 7, and
      caspase 12. In addition, the result of monodansylcadaverine staining indicated
      that LBP significantly inhibited DDP-induced autophagosome formation in MLTC-1
      cells. Moreover, immunofluorescences and Western blot assays demonstrated that
      LBP reversed DDP-induced LC3II and Atg5 upregulation in MLTC-1 cells. Finally,
      the data of enzyme-linked immunosorbent assay showed that LBP markedly recovered
      MLTC-1 cells testosterone level even in the presence of DDP. Conclusion: Thus, we
      suggest that LBP protected MLTC-1 cells against DDP via regulation of ERS
      mediated apoptosis and autophagy.

PMID- 30288023
TI  - Design and development of Nrf2 modulators for cancer chemoprevention and therapy:
      a review.
AB  - A major cell defense mechanism against oxidative and xenobiotic stress is
      mediated by the Nrf2/Keap1 signaling pathway. The Nrf2/Keap1 pathway regulates
      gene expression of many cytoprotective and detoxifying enzymes, thus playing a
      pivotal role in maintaining redox cellular homeostasis. Many diseases including
      cancer have been closely related to impaired Nrf2 activity. Targeting Nrf2 and
      modulating its activity represents a novel modern strategy for cancer
      chemoprevention and therapy. In this review, different design strategies used for
      the development of Nrf2 modulators are described in detail. Moreover, the main
      focus is on important and recently developed Nrf2 activators and inhibitors,
      their in vitro and in vivo studies, and their potential use as chemopreventive
      agents and/or cancer therapeutics.

PMID- 30288026
TI  - Cancer patients treated with intravenous chemotherapy for the first time. What
      are their needs? What do they lack? A qualitative-quantitative mixed approach.
AB  - Introduction: The announcement of cancer coupled with initiation of its treatment
      impacts patients' psychological and physical states as well as their lifestyles.
      The objective of this study was to identify and confirm the needs of patients
      starting off on anticancer chemotherapy treatment. Methods: This study was based
      on a qualitative-quantitative mixed method. In 2009, a qualitative study was
      conducted at the Lucien Neuwirth Cancer Institut for cancer patients undergoing
      intravenous chemotherapy for the first time. Exploratory and semi-directed
      interviews were carried out by a sociologist. In 2014, a questionnaire was hetero
      administered to 100 patients starting off on chemotherapy. Results: Forty
      patients were interviewed in 2009. Ninety-seven patients answered the
      questionnaire in 2014. Food was a theme that was identified by a majority of
      patients in 2009 (13/40) and confirmed in 2014: 63% needed help in identifying
      favorable food and 67% in identifying those that had to be avoided. The other
      needs identified were those linked to better understanding of the treatment, of
      how it may affect the couple, its side effects, hygiene and beauty, and knowledge
      about other treatments. These needs were confirmed in 2014. New needs were
      elicited in 2014: activities and leisure (33%), psychological needs (32.6%), and
      family relations (29.9%). Conclusion: This study enabled us to identify, confirm,
      and enrich our knowledge of the needs of cancer patients starting off on
      intravenous chemotherapy. These results led to the modification of an existing
      patient education program for these patients, in order to fulfill their needs in
      an updated and tailored manner.

PMID- 30288027
TI  - Consumer-related factors influencing antidepressant adherence in unipolar
      depression: a qualitative study.
AB  - Purpose: To explore factors which facilitate and negatively impact adherence, at
      initiation, implementation and discontinuation phases of adherence to
      antidepressant medicines. Patients and methods: Semi-structured, face-to-face
      interviews were conducted with patients suffering from unipolar depression. The
      digitally audio-recorded and transcribed verbatim were used. Transcripts were
      thematically content analyzed and data managed using N-Vivo software. Results:
      Twenty-three interviews were conducted. The predominant factors facilitating
      initiation of therapy included self-motivation and severity of depression.
      Factors aiding persistence with therapy included belief in, and effectiveness of,
      antidepressants. Stigma and fear of adverse events inhibited initiation of
      therapy, whilst adverse events and ineffectiveness of antidepressants contributed
      to discontinuation. Patients with strong perceptions of the necessity and few
      concerns about antidepressants were more likely to adhere to treatment at all
      phases of adherence. Conclusion: Different factors influence medication adherence
      at the different phases of adherence. These factors were based on individual
      perceptions about depression and its treatment, and actual experiences of
      antidepressant treatment. This information should be considered by health care
      professionals in delivering targeted and tailored interventions to foster
      adherence. Strategies to address medication non-adherence in unipolar depression
      patients should consider the phase of adherence and individual perceptions about
      depression and its treatment, along with previous experiences with treatment for
      depression.

PMID- 30288028
TI  - Patient-doctor relationship and adherence to capecitabine in outpatients of a
      German comprehensive cancer center.
AB  - Purpose: The prescribing of oral chemotherapy agents has introduced the new
      challenge of ensuring patients' adherence to therapy. Aspects of a close patient
      doctor relationship are reported to be correlated with adherence to oral
      anticancer drugs, but data on capecitabine are scarce. Patients and methods:
      Sixty-four outpatients with a diagnosis of cancer and prescribed capecitabine
      were recruited from a German Comprehensive Cancer Center. We used the Patient
      Doctor Relationship Questionnaire (PDRQ-9), the Medical Adherence Rating Scale
      (MARS), the Beliefs about Medicines Questionnaire (BMQ), and the Satisfaction
      with Information about Medicines Scale (SIMS) to assess patients' perceptions and
      behavior. Medical data were extracted from the charts. Results: Non-adherence was
      reported by 20% of the 64 participants. The perceived quality of the patient
      doctor relationship was high in general, but it did not emerge as a predictor of
      adherence in our survey (odds ratio [OR]=0.915, P=0.162, 95% CI=0.808-1.036).
      However, beliefs about medicine (OR=1.268, P<0.002; 95% CI=1.090-1.475) as well
      as satisfaction with information about medicine (OR=1.252, P<0.040, 95% CI=1.010
      1.551) were predictors of adherence and the quality of the patient-doctor
      relationship was correlated with both variables (r=0.373, P=0.002 for SIMS sum
      score; r=0.263, P=0.036 for BMQ necessity/concern difference). Overall, adherence
      to capecitabine was high with a conviction that the therapy is necessary.
      However, concerns were expressed regarding the long-term effect of capecitabine
      use. Patients have unmet information needs regarding interactions of capecitabine
      with other medicines and the impairment of their intimate life. Conclusions: In
      order to ensure adherence to capecitabine, our results seem to encourage the
      default use of modern and perhaps more impersonal means of information brokerage
      (eg, email, internet). However, the contents of some of patients' informational
      needs as well as the associations of patients' beliefs and satisfaction about the
      information received suggest a benefit from a trustful patient-doctor
      relationship.

PMID- 30288029
TI  - Caregivers' misperception of the severity of hip fractures.
AB  - Purpose: The aim of our study was to evaluate how the caregiver of a hip fracture
      patient perceives the patient's health status and autonomy in the period
      immediately preceding the acute event and whether these judgments are actually in
      line with the prognosis predicted by the medical team caring for the patient in
      the rehabilitation structure. Patients and methods: We enrolled 147 patients of
      both sexes, aged >=65 years, who were referred to our center following surgical
      treatment of hip fractures of various nature. At the beginning of the
      rehabilitation program, each patient's caregiver was asked to complete the
      Blaylock Risk Assessment Screening Score (BRASS) questionnaire. The same
      questionnaire was compiled contemporaneously by the doctor taking care of the
      patient. Results: Analysis of the data shows that the caregivers tend to assign
      lower scores than the doctor, with a mean difference in agreement with the Bland
      Altman plot of -2.43, 95% CI=-2.93 to -1.93, t-test P<0.001. Furthermore,
      differences in objectivity emerge in the evaluation of the clinical problems of
      the patient in a borderline clinical condition. Conclusion: This study revealed
      that caregivers systematically misperceive the clinical situation of hip fracture
      patients prior to the acute event. Altered perception of such an important factor
      can lead to a general lack of satisfaction with the outcome achieved by the
      patient at the end of the rehabilitation process. We therefore believe that an
      adequate, effective communication between the people making up the health care
      team and the patient's social and family network is the foundation of the
      rehabilitation process. It is precisely on this foundation that the individual's
      care and assistance need to be assembled.

PMID- 30288030
TI  - Patients' satisfaction and subjective happiness after refractive surgery for
      myopia.
AB  - Purpose: The purpose of this study was to assess patients' satisfaction and
      change in subjective happiness after laser-assisted in situ keratomileusis
      (LASIK). Patients and methods: This was a retrospective cross-sectional study of
      307 patients (mean age, 34.3 years; range, 20-63 years) who underwent bilateral
      LASIK surgery and ocular examinations, including subjective refraction and visual
      acuity axial length measurements at Minamiaoyama Eye Clinic. Patients also
      completed questionnaires on their satisfaction with the surgery, and on the
      subjective happiness scale (SHS) within 1 month before and 1 month after surgery.
      A multiple regression analysis was performed to determine the independent
      predictors of the SHS score. Results: In total, 91.2% of the patients were
      satisfied with surgery (very satisfied: n=155; satisfied: n=125). The SHS score
      increased postoperatively from 5.2+/-0.9 to 5.3+/-0.9 (P<0.001). The multiple
      regression analysis revealed that the preoperative SHS score (beta=0.77; P<0.001)
      and satisfaction with surgery (beta=-0.11; P=0.05) were predictors of
      postoperative SHS score. Conclusion: LASIK may contribute to increased patient
      happiness.

PMID- 30288031
TI  - Patient activation for self-management is associated with health status in
      patients with atrial fibrillation.
AB  - Background: Higher levels of patient activation for self-managing health are
      associated with positive clinical and health care utilization outcomes.
      Identifying a patient's activation level can guide clinicians to tailor
      interventions to improve their health. Effective self-management of atrial
      fibrillation (AF) requires patient activation to participate in treatment
      decisions, prevent complications, and manage risk factors. Yet, little is known
      about activation in patients with AF. The purpose of this descriptive study was
      to identify patient activation levels and factors associated with activation in
      patients with AF. Methods: Patients (N=123), 66% male, with a mean (SD) age of
      59.9 (11.3) years seeking treatment for AF at an arrhythmia clinic completed the
      Patient Activation Measure (PAM), Atrial Fibrillation Severity Scale, Knowledge
      about Atrial Fibrillation test, Hospital Anxiety Depression Scale, Godin Leisure
      Time Exercise Questionnaire, and Patient Assessment of Chronic Illness Care.
      Sociodemographic and clinical data were obtained from medical records. PAM scores
      were categorized into Levels 1-4. Associations among patient-reported outcomes,
      sociodemographic, and clinical variables were analyzed using Fisher's exact tests
      and Kruskal-Wallis procedures. Results: The PAM scores of nearly half (45.5%) of
      the patients were at Level 3, while the scores of 38% were at Level 4. Male sex
      (P=0.02), higher education (P=0.004), being employed (P=0.005), lower body mass
      index (P=0.03), tobacco abstinence (P=0.02), less AF symptom burden (P=0.006),
      less depression (P<=0.0001) and anxiety (P=0.006), greater knowledge of AF
      (P=0.01), and higher levels of physical activity (P=0.02) were associated with
      higher activation levels. Conclusion: Higher levels of patient activation in
      those with AF were associated with a more positive health status and educational
      attainment. Additional research to describe activation in patients with AF is
      warranted to identify patients at risk for low activation and to tailor
      interventions to activation level.

PMID- 30288032
TI  - Feasibility and willingness to pay for dengue vaccine in the threat of dengue
      fever outbreaks in Vietnam.
AB  - Background: The escalation of dengue fever (DF) cases in recent years and the
      occurrence of a large-scale DF outbreak in 2017 underline the importance of
      dengue vaccines in Vietnam. Given the potential benefits of the dengue vaccines
      and the need for copayment by the private sector, this study aims to evaluate the
      willingness to pay (WTP) for the dengue vaccines in patients with DF in Northern
      Vietnam. Methods: A cross-sectional study was conducted on 330 in-and-out
      patients with DF admitted to the Bach Mai Hospital. We used the contingent
      valuation method to evaluate the WTP for dengue vaccines. Socioeconomic and
      clinical characteristics were also investigated. Multivariate interval and
      logistic regression models were used to estimate the average amount of WTP and
      identify the factors associated with the WTP. Results: Around 77.3% patients were
      willing to pay an average amount of US$ 67.4 (95% CI=57.4-77.4) for the vaccine.
      People of higher ages, those having health insurance, those traveling in the past
      15 days or suffering from anxiety/depression were less likely to be willing to
      pay for the dengue vaccine. However, people having a longer duration of DF or
      having problems with mobility were positively associated with WTP for the dengue
      vaccine. Patients educated to more than high school levels (Coeff.=31.31; 95%
      CI=3.26-59.35), those in the richest quintile (Coeff.=62.76; 95% CI=25.40;
      100.13), or those having a longer duration of the disease (Coeff.=6.18; 95%
      CI=0.72-11.63) were willing to pay a higher amount. Conclusion: This study
      highlights a relatively high rate and amount of WTP for the dengue vaccine among
      patients with DF. Psychological counseling services as well as educational
      campaigns should be undertaken to improve the WTP for the vaccine. Moreover,
      government subsidies should be given to increase the coverage of the vaccine in
      the future, especially for the poor.

PMID- 30288033
TI  - A multivariate investigation into the relationship between pharmaceutical
      characteristics and patient preferences of bioequivalent ibuprofen tablets.
AB  - Background: In Spain the price of all ibuprofen 600 mg tablet generic products is
      the same due to reimbursement existing rules so for the patient there is not any
      economic incentive to choose a particular one. Bearing in mind that the quality
      of generic products should be similar, it could be questioned if differences in
      patient preferences evaluated as sales could be related to differences on their
      pharmaceutical properties. The aims of this work were to study the variability on
      the pharmaceutical characteristics of marketed bioequivalent tablet formulations
      and its impact on patient preferences. Methods: Thirty-six batches corresponding
      to fourteen different generic products were chosen among the best-selling
      products of the Spanish market in the years 2011 and 2015 and were compared to
      the reference product. The effect on patient preferences of six variables was
      studied through a multivariate analysis. The first two variables were marketing
      characteristics: 1) years in the market and 2) the number of other generic
      products marketed by the same manufacturer, which could be related to the size
      and service provided by the manufacturer. The other four variables studied were
      pharmaceutical tablet properties: 3) mean weight, 4) hardness, 5) disintegration,
      and 6) dissolution. A multiple linear regression analysis was performed to
      identify the effect on sales of the six variables studied. Results: The
      disintegration time was the most significant (P=0.018) factor affecting the sales
      of Ibuprofen tablets which may be related to the onset of action. Conclusion: The
      faster the tablet disintegration, the higher its sales. Two possible explanations
      are suggested: 1) the most specialized ibuprofen tablet manufacturer considers
      fast disintegration as a key parameter and/or 2) habitual consumers of ibuprofen
      can detect small differences on the onset of action among different marketed
      formulations. In this work, all marketed ibuprofen tablets comply with the
      pharmacopoeia specifications.

PMID- 30288034
TI  - Time preference, outcome expectancy, and self-management in patients with type 2
      diabetes.
AB  - Background: Patient self-management is crucial to prevent complications and
      mortality in type 2 diabetes. From an economic perspective, time preference
      predicts short-sighted decision making and thus might help to explain non
      adherence to self-anagement recommendations. However, recent studies on this
      association have shown mixed results. Purpose: In this study, we tested whether
      the combination of time preference and outcome expectancy can improve the
      predictions of self-management behavior. Patients and methods: Data from 665
      patients with type 2 diabetes were obtained from the cross-sectional KORA
      (Cooperative Health Research in the Region of Augsburg) GEFU 4 study. Time
      preference and outcome expectancy were measured by one question each, which were
      answered on a 4-point Likert scale. Their association with six self-managing
      behaviors was tested in logistic and linear regression analyses. Likewise, we
      examined the association between self-management and the interaction of outcome
      expectancy and time preference. Results: A high time preference was associated
      with a significantly lower sum of self-management behaviors (beta=-0.29, 95% CI [
      0.54, -0.04]). Higher outcome expectancy was associated with a higher self
      management score (beta=0.21, 95% CI [-0.03, 0.45]). The interaction model showed
      that low time preference was only associated with better self-management when
      combined with a high outcome expectancy (beta=0.05, 95% CI [-0.28, 0.39] vs
      beta=0.27, 95% CI [-0.09, 0.63]). Conclusion: Time preference and outcome
      expectancy are interrelated predictors of patient self-management and could be
      used to identify and to intervene on patients with a potentially poor self
      management.

PMID- 30288035
TI  - Isotemporal substitution of sedentary time with physical activity and its
      associations with frailty status.
AB  - Objectives: Recently, isotemporal substitution has been developed to substitute
      activity time for an equivalent amount of another activity. This study employed
      this method to demonstrate the effects of replacing sedentary behavior (SB) time
      with an equivalent amount of light-intensity physical activity (LPA) and moderate
      to-vigorous intensity physical activity (MVPA) on the risk for different
      severities of frailty. Methods: A total of 886 older adults (average age 73.6
      years, female 70%) participated in this cross-sectional study. Frailty status was
      assessed according to the cardiovascular health study criteria. Main outcome
      measures: Wrist-worn accelerometers were used to measure SB, LPA, and MVPA.
      Isotemporal substitution models were applied to show the estimated effects of
      substituting 30 min of SB with an equal amount of time spent in LPA or MVPA on
      the risk for pre-frailty and frailty. Results: The physical activity level and SB
      were not associated with the incidence of pre-frailty. However, a 16% (OR: 0.84;
      95% CI: 0.78-0.90) and 42% (OR: 0.58; 95% CI: 0.37-0.92) decrease in frailty risk
      was noted when SB was substituted with LPA and MVPA, respectively, in the crude
      model. In the adjusted model, the significant effect was sustained for LPA (OR:
      0.86; 95% CI: 0.80-0.92) but not for MVPA (OR: 0.74; 95% CI: 0.47-1.17).
      Conclusions: This study indicates that replacing 30 min of SB with an equivalent
      amount of LPA decreases the risk for frailty in older adults. Moreover,
      increasing LPA seems more feasible than increasing MVPA in older adults, with
      substantial benefit.

PMID- 30288036
TI  - The influence of carbon dioxide field flooding in mitral valve operations with
      cardiopulmonary bypass on S100beta level in blood plasma in the aging brain.
AB  - Introduction: The risk of air microembolism during cardiopulmonary bypass (CPB)
      is high and influences the postoperative outcome, especially in elderly patients.
      The use of carbon dioxide (CO2) atmosphere during cardiac surgery may reduce the
      risk of cerebral air microembolism. The aim of our study was to assess the
      influence of CO2 field flooding on microembolism-induced brain damage assessed by
      the level of S100beta protein, regarded as a marker of brain damage. Materials
      and methods: A group of 100 patients undergoing planned mitral valve operation
      through median sternotomy using standard CPB was recruited for the study.
      Echocardiography was performed prior to and after the CPB. CO2 insufflation at 6
      L/minute was conducted in the study group. Blood samples for S100beta protein
      analysis were collected after induction of anesthesia, 2 hours after aorta de
      clamping, and 24 hours after operation. Results: The S100beta level in blood
      plasma did not differ significantly between the study and the control group
      (0.13+/-0.08 ug/L, 1.12+/-0.59 ug/L, and 0.26+/-0.23 ug/L and 0.18+/-0.19 ug/L,
      1.31+/-0.62 ug/L, and 0.23+/-0.12 ug/L, P=0.7, 0.14, and 0.78). The mean increase
      of the S100beta concentration was 13% lower in the group with CO2 protection than
      in the control group (0.988 ug/L vs 1.125 ug/L), although statistically
      insignificant. Tricuspid valve annuloplasties (TVAs) had significant impact on
      the increase in S100beta concentration in the treatment group after 24 hours (TVA
      [-] 0.21+/-0.09 vs TVA [+] 0.42+/-0.42, P=0.05). In patients <60 years, there
      were significant differences in the S100beta level 2 and 24 hours after the
      procedure (1.59+/-0.682 ug/L vs 1.223+/-0.571 ug/L, P=0.048, and 0.363+/-0.318
      ug/L vs 0.229+/-0.105 ug/L, P=0.036) as compared with younger patients.
      Conclusion: The increase in S100beta concentration was lower in the group with
      CO2 protection than in the control group. Age and an addition of TVA
      significantly influenced the level of S100beta concentration in the tests
      performed 2 hours after aortic clamp release.

PMID- 30288037
TI  - A comparative analysis of errors in inhaler technique among COPD versus asthma
      patients.
AB  - Purpose: This study was designed to evaluate errors in inhaler technique in COPD
      vs asthma patients and to investigate the association of poor inhaler technique
      with patient demographics and clinical variables. Patients and methods: A total
      of 509 adult patients with COPD (n=328) or asthma (n=181) who were currently
      using an inhaler device were included in this study. Data on patient
      demographics, duration of disease, type and duration of inhaler therapy, and
      assessment of inhaler technique were recorded. Results: Metered dose inhaler
      (MDI) was the most common type of inhaler used by a similarly high percentage of
      patients in both COPD (83.2%) and asthma (77.3%) groups. Failure to exhale before
      inhaling through device (75.8% and 68.5% for MDIs; 73.2% and 71.8% for
      Aerolizer(r)/Handihaler(r); 53.1% and 66.7% for Turbuhaler(r)) was the most
      common error in inhaler technique, in both COPD and asthma groups. Device
      specific errors in inhaler techniques were more common in asthma patients as
      compared with COPD patients, particularly for MDIs (P-values ranged from 0.046 to
      0.0005), as associated with female gender (failure to press the buttons on both
      sides of Aerolizer(r)/Handihaler(r), P=0.006), shorter duration of disease
      (failure to hold MDI or head in a vertical position, P<0.001, and to keep
      Turbuhaler(r) upright, P=0.005), and shorter duration of inhaler usage (failure
      to hold head in a vertical position during MDI usage, P=0.006, and to keep
      Turbuhaler(r) upright, P=0.012). Conclusion: In conclusion, our findings revealed
      that errors in inhaler technique in terms of inhalation maneuvers and device
      handling were similarly common in COPD and asthma patients. Errors in certain
      device handling maneuvers, particularly with MDIs, were more common among asthma
      patients than among COPD patients and associated with female gender and shorter
      durations of disease and inhaler therapy.

PMID- 30288039
TI  - Effects of PEG surface density and chain length on the pharmacokinetics and
      biodistribution of methotrexate-loaded chitosan nanoparticles.
AB  - Background: One of the most important aspects of drug delivery is extended
      nanoparticle (NP) residence time in vivo. Herein, we report a series of
      methotrexate (MTX)-loaded chito-san (CS) NPs coated with differently sized
      methoxy polyethylene glycol (mPEG) at different mPEG surface densities. Materials
      and methods: MTX was incorporated into NPs (112.8-171.2 nm in diameter) prepared
      from the resulting mPEG-g-CS. The NPs had a zeta potential of +7.4-35.0 mV and
      MTX loading efficiency of 17.1%-18.4%. MTX/mPEG-g-CS NPs showed an initial burst
      release of MTX followed by a sustained-release profile in PBS at pH 7.4. Results:
      The in vitro cellular uptake study showed that MTX accumulation in J774A.1
      macrophage cells decreased with increasing the mPEG surface density or the mPEG
      molecular weight. The pharmacokinetic study on Sprague Dawley rats revealed an
      increase in AUC0-72 h (area under the plasma drug concentration-time curve over a
      period of 72 hours) with increasing the mPEG surface density or the mPEG
      molecular weight and a linear correlation between the mPEG surface density and
      AUC0-72 h. Conclusion: The biodistribution study on Institute of Cancer Research
      (ICR) mice revealed that MTX/mPEG-g-CS NPs significantly enhanced blood
      circulation time in the body and decreased accumulation in liver, spleen, and
      lung. These results suggest the potential of the mPEG-g-CS NPs as a promising
      candidate for drug delivery.

PMID- 30288040
TI  - Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of
      lymphoma cell growth and synchronous reduction of cardiac toxicity.
AB  - Purpose: Cardiac side effects of doxorubicin (Dox) have limited its clinical
      application. The aim of this study was to explore new Dox-loaded dextran-based
      nano-carriers (NCs) in efficiently targeting tumor growth with less cardiac
      toxicity. Methods: Inspired by recent reports that polymeric NCs could function
      as sustained, controlled and targeted drug delivery systems, we developed Dox
      loaded NCs which displayed a 2-fold release ratio of Dox in the mimic tumor site
      condition (pH 5.0 with 10 mM glutathione, GSH) as much as that in systemic
      circulation condition (pH 7.4). Results: Lymphoma cells treated with Dox-NCs had
      significantly higher intracellular Dox concentrations and more apoptotic
      induction, with lower P-gp expression, when compared with those treated with Dox
      alone. The identified mechanism of action, apoptosis, was triggered through
      survivin reduction and caspase-3 activation. Even in the Dox-resistant cells, Dox
      NCs could significantly inhibit cell growth and induce apoptosis. In murine
      lymphoma xenograft models, Dox-NCs also remarkably significantly retarded tumor
      growth, assessed by murine weight, and demonstrated less cytotoxicity.
      Noticeably, apoptotic myocardial cells were decreased in the Dox-NCs-treated
      group, when compared with the control group, which was consistent with low
      intracellular Dox concentration in the cardiac cell line H9C2. Conclusion: Dox
      NCs showed an anti-lymphoma effect with reduced cardiac toxicity in both in vivo
      and in vitro models and, therefore, could be a potential therapeutic agent in the
      treatment of lymphoma.

PMID- 30288041
TI  - Silver-doped graphene oxide nanocomposite triggers cytotoxicity and apoptosis in
      human hepatic normal and carcinoma cells.
AB  - Introduction: Graphene oxide nanoparticles have been widely used in industry and
      biomedical fields due to their unique physicochemical properties. However,
      comparative cytotoxicity of silver-doped reduced graphene oxide (rGO-Ag)
      nanoparticles on normal and cancerous liver cells has not been well studied yet.
      Materials and methods: This study aimed at determining the toxic potential of rGO
      Ag nanocomposite on human liver normal (CHANG) and cancer (HepG2) cells. The rGO
      Ag nanocomposite was characterized by using different advanced instruments,
      namely, dynamic light scattering, scanning electron microscope, and transmission
      electron microscope. Results: The rGO-Ag nanocomposite reduced cell viability and
      impaired cell membrane integrity of CHANG and HepG2 cells in a dose-dependent
      manner. Additionally, it induced reactive oxygen species generation and reduced
      mitochondrial membrane potential in both cells in a dose-dependent manner.
      Moreover, the activity of oxidative enzymes such as lipid peroxide, superoxide
      dismutase, and catalase were increased and glutathione was reduced in both cells
      exposed to rGO-Ag nanocomposite. Pretreatment with N-acetylcysteine inhibited
      cytotoxicity and reactive oxygen species generation in CHANG and HepG2 cells
      exposed to rGO-Ag nanocomposite (50 ug/mL). DNA damage was determined by Comet
      assay and maximum DNA damage occurred at rGO-Ag nanocomposite (25 ug/mL) for 24
      h. It is also valuable to inform that HepG2 cells appear to be slightly more
      susceptible to rGO-Ag nanocomposite exposure than CHANG cells. Conclusion: This
      result provides a basic comparative toxic effect of rGO-Ag nanocomposite on
      hepatic normal and cancerous liver cells.

PMID- 30288038
TI  - Nanoparticles in tissue engineering: applications, challenges and prospects.
AB  - Tissue engineering (TE) is an interdisciplinary field integrating engineering,
      material science and medical biology that aims to develop biological substitutes
      to repair, replace, retain, or enhance tissue and organ-level functions. Current
      TE methods face obstacles including a lack of appropriate biomaterials,
      ineffective cell growth and a lack of techniques for capturing appropriate
      physiological architectures as well as unstable and insufficient production of
      growth factors to stimulate cell communication and proper response. In addition,
      the inability to control cellular functions and their various properties
      (biological, mechanical, electrochemical and others) and issues of biomolecular
      detection and biosensors, all add to the current limitations in this field.
      Nanoparticles are at the forefront of nanotechnology and their distinctive size
      dependent properties have shown promise in overcoming many of the obstacles faced
      by TE today. Despite tremendous progress in the use of nanoparticles over the
      last 2 decades, the full potential of the applications of nanoparticles in
      solving TE problems has yet to be realized. This review presents an overview of
      the diverse applications of various types of nanoparticles in TE applications and
      challenges that need to be overcome for nanotechnology to reach its full
      potential.

PMID- 30288043
TI  - Subjective memory complaint as a useful tool for the early detection of
      Alzheimer's disease.
AB  - Purpose: Despite their high prevalence in Alzheimer's disease (AD), and the
      increasing level of concern they have generated, subjective memory complaints
      (SMCs) are poorly understood. This study investigated the accuracy with which SMC
      can separate mild cognitive impairment (MCI) and early AD from cognitive normal
      (CN), and explored whether the discrimination ability is similar to or better
      than that of the Mini-Mental State Exam (MMSE). Patients and methods: This study
      recruited 175 CN subjects, 52 with MCI, and 66 with probable AD aged 60 years or
      older. To test the independent contributions of SMC and MMSE scores to the
      classification of cognitive status (CN vs MCI or early AD), logistic regression
      analyses were performed, adjusting for the following potential confounding
      variables: age, gender, Frontal Assessment Battery score, modified Hachinski
      Ischemic Scale score, and apolipoprotein E epsilon4 status. Receiver operating
      characteristic (ROC) curve analyses were used to determine the discrimination
      accuracy of SMC and MMSE scores, and area under the ROC curve (AUROC) was also
      calculated. Results: In the highly educated (>=7 years), nondepressed (Geriatric
      Depression Scale <=15) subgroup, SMC showed good accuracy in discriminating
      cognitively impaired subjects from CN after adjusting for potential confounding
      variables (the AUROC of the adjusted SMC was 0.841 for MCI discrimination, and it
      was 0.858 for MCI plus early AD discrimination). Both SMC and MMSE scores
      significantly contributed to differentiating between CN and MCI (OR=2.372, 95%
      CI=1.086-5.177; OR=0.730, 95% CI=0.566-0.941, respectively) after adjusting for
      the same covariates. However, in the highly educated and nondepressed subgroups,
      SMC showed significant predictive power for MCI from CN (OR=3.119, 95% CI=1.190
      8.176; OR=3.328, 95% CI=1.320-8.396, respectively), whereas MMSE scores did not.
      Conclusion: Our findings support the usefulness of SMC, which was comparable or
      even superior to MMSE scores, for detecting MCI or early AD.

PMID- 30288044
TI  - Risk of hip fracture in patients on dialysis or kidney transplant: a meta
      analysis of 14 cohort studies.
AB  - Purpose: We aimed to conduct a meta-analysis of published cohort studies to
      evaluate the risk of hip fracture in patients undergoing dialysis or kidney
      transplantation (KT). Methods: We identified relevant studies by searching
      PubMed, EMBASE and Google Scholar databases from their inception to December 31,
      2017. Cohort studies evaluating risk of hip fractures in patients undergoing
      dialysis or KT were considered included. The methodological quality of the cohort
      studies was assessed using the modified Newcastle-Ottawa scale. Results: In our
      meta-analysis of 14 retrospective cohort studies, a total of more than 1.5
      million patients undergoing dialysis or KT were included, of whom more than
      30,000 had hip fractures. After the merger, the proportion of hip fractures was
      1.92% (95% CI, 1.38%-2.46%) with significant heterogeneity (I 2=99.9%, P=0.000)
      in all patients, and the incidence rate of hip fractures (per 1,000 person-years)
      was 8.95 (95% CI, 4.05-13.85) with significant heterogeneity (I 2=99.9%,
      P=0.000). The pooled relative risks (RR) value for dialysis patients compared
      with the general population were 6.35 (95% CI, 4.53-8.88) for male and 5.57 (95%
      CI, 4.44-6.99) for female. The pooled RR value for hemodialysis (HD) patients
      compared with peritoneal dialysis (PD) patients was 1.39 (95% CI, 1.13-1.70) with
      no heterogeneity (I 2=0.0%, P=0.763). Conclusion: In conclusion, the present meta
      analysis reveals that about 2% of dialysis or KT patients go on to sustain a hip
      fracture during follow-up, with the overall hip fracture incidence rates being
      8.95 per 1,000 person-years. The overall risk of hip fracture was more than 5
      fold higher in dialysis patients than in the general population. Among patients
      on PD, HD, and KT, HD and KT patients had the highest and the lowest risk of hip
      fractures, respectively.

PMID- 30288042
TI  - A drug eluting poly(trimethylene carbonate)/poly(lactic acid)-reinforced
      nanocomposite for the functional delivery of osteogenic molecules.
AB  - Background: Poly(trimethylene carbonate) (PTMC) has wide biomedical applications
      in the field of tissue engineering, due to its biocompatibility and
      biodegradability features. Its common manufacturing involves photofabrication,
      such as stereolithography (SLA), which allows the fabrication of complex and
      controlled structures. Despite the great potential of SLA-fabricated scaffolds,
      very few examples of PTMC-based drug delivery systems fabricated using photo
      fabrication can be found ascribed to light-triggered therapeutics instability,
      degradation, side reaction, binding to the macromers, etc. These concerns
      severely restrict the development of SLA-fabricated PTMC structures for drug
      delivery purposes. Methods: In this context, we propose here, as a proof of
      concept, to load a drug model (dexamethasone) into electrospun fibers of
      poly(lactic acid), and then to integrate these bioactive fibers into the photo
      crosslinkable resin of PTMC to produce hybrid films. The hybrid films' properties
      and drug release profile were characterized; its biological activity was
      investigated via bone marrow mesenchymal stem cells culture and differentiation
      assays. Results: The polymer/polymer hybrids exhibit improved properties compared
      with PTMC-only films, in terms of mechanical performance and drug protection from
      UV denaturation. We further validated that the dexamethasone preserved its
      biological activity even after photoreaction within the PTMC/poly(lactic acid)
      hybrid structures by investigating bone marrow mesenchymal stem cells
      proliferation and osteogenic differentiation. Conclusion: This study demonstrates
      the potential of polymer-polymer scaffolds to simultaneously reinforce the
      mechanical properties of soft matrices and to load sensitive drugs in scaffolds
      that can be fabricated via additive manufacturing.

PMID- 30288045
TI  - Changes in cardiovascular risk and clinical outcomes in a HIV/AIDS cohort study
      over a 1-year period at a specialized clinic in Mexico.
AB  - Introduction: The third report of the National Cholesterol Education Program
      guidelines recommends calculating the 10-year morbidity of atherosclerotic
      cardiovascular disease (ASCVD) using risk calculators when treating high blood
      cholesterol in adults. We analyzed the changes in cardiovascular risk (CVR) among
      Mexican patients with HIV. Patients and methods: This observational, prospective
      cohort study compared the CVR after 1 year of antiretroviral treatment among 460
      HIV patients from a Mexican clinic. Changes using the ASCVD risk estimator and
      changes in clinical outcomes were analyzed. The results were categorized as low
      or high CVR using a cutoff of 7.5%. Results: The CVR initially had a median of
      2.3% (interquartile range [IQR]: 1%-4.8%), which changed to 2.4% (IQR: 1.5%-5.5%)
      after 1 year (P=0.001). After CVR stratification, we found that 84.3% of the
      patients had a low CVR, and 18% in this subgroup had metabolic syndrome (MS).
      Moreover, 15.7% had high CVR, and 47% in this subgroup had MS. The 4.3% of
      patients had an increase in CVR from the low to high subgroup, and 2.6% had a
      decrease in CVR from the high to low subgroup. Out of all patients, 22.3% had MS.
      Conclusion: More than 50% of the population had an increase in CVR after 1 year.
      Of these patients, 4.3% changed from the low to high CVR group. Although the
      guidelines proposed different time periods for performing CVR estimations, this
      study showed that such assessments offered valuable clinical data over a
      relatively short-term period.

PMID- 30288047
TI  - Efficacy and safety of apatinib treatment for gastric cancer, hepatocellular
      carcinoma and non-small cell lung cancer: a meta-analysis.
AB  - Apatinib (Aitan(r), brand name in China) is a new anti-antiangiogenic agent that
      has recently been approved for the treatment of advanced gastric cancer (GC) in
      China. Nevertheless, its therapeutic efficacy against other types of advanced
      solid tumors remains unclear. This meta-analysis examines the short-term efficacy
      and safety of apatinib or combination therapy for GC, hepatocellular carcinoma
      (HCC) and non-small-cell lung cancer (NSCLC); and provides a discussion of its
      anti-angiogenesis therapy applications. Seven clinical studies met the inclusion
      criteria. The treatment of cancers using apatinib was more successful compared to
      therapy without apatinib. Both objective response rates (ORRs) and disease
      control rates (DCRs) were significantly improved in the apatinib group compared
      to those in the control group (RR=2.18, 95% CI 1.30-3.65; RR=2.09, 95% CI 1.21
      3.60). The DCR of 850 mg qd and 750 mg qd were higher than those in the control
      group (P<0.05). Based on the short-term acute adverse reactions of apatinib,
      significant differences between groups were found for hypertension, urine
      protein, hand foot syndrome, and gastrointestinal reactions (diarrhea), while no
      significant differences were found for myelosuppression, nausea and vomiting.
      Moreover, the results showed that apatinib prolonged patient survival (HR=0.38,
      95% CI: 0.28-0.52), and the effect was more pronounced in patients treated with
      750 mg qd or 850 mg qd of apatinib than in those treated with a dose of <=500 mg
      qd. Additionally, compared to its second-line application, the third-line
      application was shown to further reduce the risk ratio in patients. Furthermore,
      overall survival was longer in patients treated with apatinib. Apatinib was shown
      to have certain short-term effects and survival benefits on GC, HCC, and NSCLC
      with controllable adverse effects.

PMID- 30288046
TI  - Home care workers in heart failure: a systematic review.
AB  - Background: Home care workers (HCWs), which include home health aides and
      personal care aides, are increasingly used by heart failure (HF) patients for
      post-acute care and long-term assistance. Despite their growing presence, they
      have largely been left out of HF research and interventions. This systematic
      review was aimed to 1) describe utilization patterns of HCWs by adults with HF,
      2) examine the effect of HCWs on HF outcomes, and 3) review HF interventions that
      involve HCWs. Methods: Five electronic databases (Ovid MEDLINE, Ovid EMBASE,
      Cochrane Library [Wiley], CINAHL [EBSCO], and AgeLine [EBSCO]) were searched from
      inception through August 4, 2017. The yield was screened using prespecified
      inclusion and exclusion criteria. Two authors independently reviewed references
      and a third reviewer acted as an arbitrator when needed. Data were extracted from
      articles that met the inclusion criteria. The Downs and Black checklist was used
      for quality assessment. Due to study heterogeneity, a narrative synthesis was
      conducted. Results: Of the 7,032 studies screened, 13 underwent full-text review,
      and six met the inclusion criteria. Two descriptive studies found that adults
      with HF who live alone and have functional and cognitive deficits utilize HCWs.
      While three retrospective cohort studies examined the association between having
      an HCW post-HF hospitalization and readmission rates, their findings were
      conflicting. One quasi-experimental study found that an HCW-delivered educational
      intervention improved HF patients' self-care abilities. Overall, despite some
      significant findings, the studies assessed were of poor-to-fair quality (Downs
      and Black score range: 10-16 [28 total points]), with most lacking methodological
      rigor. Conclusion: Although HCWs are quite common, the literature on these
      paraprofessionals in HF is limited. Given the paucity of research in this area
      and the low quality of studies reviewed here, additional research is warranted on
      the potential role of HCWs in HF self-care and on outcomes among adults with HF.

PMID- 30288048
TI  - Is long interval from neoadjuvant chemoradiotherapy to surgery optimal for rectal
      cancer in the era of intensity-modulated radiotherapy?: a prospective
      observational study.
AB  - Objectives: To evaluate the impact of interval between neoadjuvant
      chemoradiotherapy (NACRT) and surgery on therapeutic and adverse effects of
      surgery, and long-term outcome of patients with locally advanced rectal cancer
      (RC), in the era of intensity-modulated radiotherapy (IMRT). Patients and
      methods: Patients diagnosed with stage II-III RC and treated with IMRT-based
      NACRT followed by radical surgery were enrolled consecutively from April 2011 to
      March 2014. The data of all the patients were collected prospectively and grouped
      according to their NACRT-to-surgery interval. The therapeutic and adverse effects
      of surgery, and survivals were compared between the patients with interval <=7
      weeks and those with interval >=8 weeks. Results: A total of 231 patients were
      eligible for analysis, including 106 cases with interval <=7 weeks and 125 cases
      with interval >=8 weeks. The therapeutic and adverse effects of surgery were
      similar between these two groups of patients. However, interval >=8 weeks
      appeared to lead to poorer overall, distant-metastasis-free and disease-free
      survivals, compared with interval <=7 weeks. The HRs were 1.805, 1.714, and 1.796
      (P-values were 0.045, 0.049, and 0.028), respectively. Conclusion: For patients
      with locally advanced RC, a long NACRT-to-surgery interval might bring a
      potential risk of increased distant metastasis rather than a better tumor
      regression in the era of IMRT.

PMID- 30288049
TI  - Distribution of CD4+ and CD8+ exhausted tumor-infiltrating lymphocytes in
      molecular subtypes of Chinese breast cancer patients.
AB  - Purpose: Breast cancer (BC) is the leading cancer affecting Chinese women;
      however, the immune microenvironment between molecular subtypes is less reported.
      This study aimed to investigate the distribution of tumor-infiltrating lymphocyte
      (TIL) subpopulations, especially exhausted CD4+ and CD8+ TILs in Chinese BC
      patients. Patients and methods: A total of 133 patients with breast invasive
      ductal carcinoma were recruited consecutively from January 1, 2012 to December
      31, 2013, and TILs were detected in H&E-stained sections. Expression profiling of
      PD-1, CD4, and CD8 was determined by immunohistochemistry on 4 um formalin-fixed
      paraffin-embedded tissue sections. The distribution of TILs was analyzed based on
      hormone receptor status and molecular subtypes. Results: PD-1+, CD4+, and CD8+
      TILs distributed differently based on molecular subtypes. Compared to Luminal A,
      triple-negative breast cancer (TNBC) patients had more PD-1+ TILs (39/high-power
      field [HPF] vs 11/HPF), PD-1+ helper T (CD4+) cells (28/HPF vs 10/HPF), and PD-1+
      cytotoxic (CD8+) T-cells (3/HPF vs 2/HPF). Conclusion: TILs are distributed
      differently based on molecular subtypes. TNBC patients exhibit more PD-1+
      exhausted TILs, representing an inhibitory immune microenvironment. PD-1/PD-L1
      pathway is a potential therapeutic target of TNBC.

PMID- 30288050
TI  - Scalp metastases as first presentation of pulmonary adenocarcinomas: a case
      report.
AB  - Cutaneous metastasis from primary visceral malignancy is a relatively uncommon
      clinical entity, with a reported incidence ranging from 0.22% to 12% of all
      malignancies. Here we report a 64-year-old asymptomatic female patient with Peutz
      Jeghers syndrome presenting with multiple scalp metastases as the initial
      manifestation secondary to lung adenocarcinoma. Subsequent lung computed
      tomography scan showed large masses involving the left upper lobe associated with
      extensive mediastinal lymphadenopathy. After treatment with an epidermal growth
      factor receptor inhibitor gefitinib, the size of the tumor in the lung reduced
      significantly and the condition of the patient also gradually improved. Our case
      demonstrated that scalp metastasis could be the first sign of an internal
      malignancy. Asymptomatic elderly patients presenting with multiple, painless,
      immobile cutaneous nodules should be considered for further investigations to
      rule out the underlying primary cause. Metastasis to the skin is often a
      preterminal event that heralds poor prognosis.

PMID- 30288051
TI  - CPEB4 promotes growth and metastasis of gastric cancer cells via ZEB1-mediated
      epithelial- mesenchymal transition.
AB  - Background: Cytoplasmic polyadenylation element-binding protein 4 (CPEB4) has
      previously been reported to be associated with biological malignancy in various
      cancers. However, its function in tumor growth and metastasis in gastric cancer
      (GC) remains obscure. Here, we explored the functional and molecular mechanisms
      by which CPEB4 influences GC. Materials and methods: The expression of CPEB4 was
      assessed using Western blot and immunohistochemistry in GC specimens. The roles
      of CPEB4 in GC cell proliferation, migration, and invasion were investigated by
      cell-counting kit-8 (CCK-8), colony formation, and EdU assay; wound-healing
      assay; and transwell assay, respectively. Quantitative real-time PCR (qRT-PCR),
      Western blot, and immunofluorescence staining were performed to detect the
      expressions of CPEB4 and epithelial-mesenchymal transition (EMT)-related markers.
      The function of CPEB4 on GC cell growth and metastasis was also determined in
      vivo through establishing subcutaneous xenograft tumor and lung metastatic mice
      model. Results: The results revealed that the expression of CPEB4 was increased
      in GC tissues compared with matched normal tissues. High expression level of
      CPEB4 was significantly associated with clinical metastasis and unfavorable
      prognosis in patients with GC. Furthermore, CPEB4 silencing remarkably inhibited
      GC cells' proliferation, invasion, and metastasis in vitro and in vivo.
      Conversely, CPEB4 overexpression achieved the opposite effects. Mechanically, we
      proved that ZEB1-mediated EMT might be involved in CPEB4-facilitated GC cells'
      proliferation, invasion, and metastasis. Conclusion: Our findings implied that
      CPEB4 expression predicted a worse prognosis in patients with GC. Besides, CPEB4
      contributed to GC cells' proliferation, migration, and invasion via ZEB1-mediated
      EMT.

PMID- 30288052
TI  - Clinical, dosimetric, and position factors for radiation-induced acute
      esophagitis in intensity-modulated (chemo)radiotherapy for locally advanced non
      small-cell lung cancer.
AB  - Purpose: The purpose of this study was to estimate the relation between acute
      esophagitis (AE) and clinical, dosimetric, and position factors in patients with
      locally advanced non-small-cell lung cancer (NSCLC) receiving intensity-modulated
      (chemo)radiotherapy. Materials and methods: A retrospective cohort analysis was
      performed to identify factors associated with Common Toxicity Criteria for
      Adverse Events grade 2 or worse AE (AE2+). A multivariable model was established
      including patient- and treatment-related variables and esophageal dose-volume
      histogram parameters. The esophagus was divided according to physiological
      anatomy, and logistic regression was used to analyze the position parameter for
      its correlation with AE2+. Results: The incidence of AE2+ was 27.5%. All models
      included gender, concurrent chemo-radiotherapy (CCRT), position parameter, and
      one of the dosimetric variables. The model with mean dose showed the best
      goodness of fit. Gender (OR=2.47, P=0.014), CCRT (OR=3.67, P=0.015), mean dose
      (OR=1.33, P<0.001), and maximum radiation position (OR=1.65, P=0.016) were
      significantly related to AE2+. Conclusion: Gender, concurrent chemotherapy,
      maximum radiation position, and mean dose were independent risk factors for AE2+.
      The upper part of the esophagus showed a higher sensitivity to radiation
      toxicity.

PMID- 30288053
TI  - All-trans retinoic acid-encapsulated, CD20 antibody-conjugated poly(lactic-co
      glycolic acid) nanoparticles effectively target and eliminate melanoma-initiating
      cells in vitro.
AB  - Purpose: Melanoma, which is initiated from melanocytes, is the most fatal type of
      skin cancer. Melanoma-initiating cells significantly contribute to the
      initiation, metastasis, and recurrence of melanoma, and CD20 is a marker of
      melanoma-initiating cells. All-trans retinoic acid (ATRA) has been demonstrated
      to induce differentiation, inhibit proliferation, and promote the apoptosis of
      cancer cells and cancer-initiating cells (CICs). However, there has been no
      report on ATRA activity against melanoma-initiating cells. In this study, we
      examined the activity of ATRA against melanoma-initiating cells and developed
      ATRA-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles, which were
      conjugated with a CD20 antibody (ATRA-PNP-CD20) for targeted delivery of ATRA to
      CD20+ melanoma-initiating cells. Materials and methods: The effects of ATRA and
      ATRA-PNP-CD20 against melanoma-initiating cells were investigated using a
      cytotoxicity assay, tumorsphere formation assay, and flow cytometry. Results:
      ATRA-PNP-CD20 had a size of 126.9 nm and a negative zeta potential. The drug
      loading capacity of ATRA-PNP-CD20 was 8.7%, and ATRA-PNP-CD20 displayed a
      sustained release of ATRA for 144 hours. The results showed that ATRA-PNP-CD20
      could effectively and specifically deliver ATRA to CD20+ melanoma-initiating
      cells, achieving superior inhibitory effects against CD20+ melanoma-initiating
      cells compared with those of free ATRA and nontargeted nanoparticles. To the best
      of our knowledge, we report for the first time a potent activity of ATRA against
      CD20+ melanoma-initiating cells, targeted drug delivery of ATRA via nanoparticles
      to melanoma-initiating cells, and the achievement of a superior inhibitory effect
      against melanoma-initiating cells by using a CD20 antibody. Conclusion: ATRA-PNP
      CD20 represents a promising tool for eliminating melanoma-initiating cells and
      shows a potential for the therapy of melanoma.

PMID- 30288054
TI  - Immunotherapy combined with epidermal growth factor receptor-tyrosine kinase
      inhibitors in non-small-cell lung cancer treatment.
AB  - In recent years, targeted therapy and immunotherapy have played important roles
      in the treatment of patients with non-small-cell lung cancer (NSCLC). Drugs that
      target epidermal growth factor receptor (EGFR) mutations (eg, gefitinib,
      erlotinib, icotinib, and osimertinib) are among the most commonly used targeted
      therapies. Afatinib is an irreversible second-generation EGFR-tyrosine kinase
      inhibitor (EGFR-TKI), and the LUX-Lung 3 trial demonstrated the superiority of
      afatinib to cisplatin and pemetrexed in the frontline treatment of treatment
      naive patients with advanced EGFR mutation adenocarcinoma of the lung. Although
      these drugs show significant therapeutic efficacy, most patients invariably
      experience disease progression resulting in death. Immunotherapy targeting
      programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) has now been approved
      for the first-line treatment of patients with advanced NSCLC. These can produce
      sustained clinical responses by reversing negative regulators of T-cell function;
      however, immunotherapy response rates remain low, and only a few patients
      ultimately benefit from this approach. Here, we discuss the potential of EGFR
      TKIs for inducing antitumor immunity and the feasibility of their combination
      with immunotherapy (including PD-1/PD-L1 inhibitors) in NSCLC patients and the
      associated challenges for clinical application.

PMID- 30288056
TI  - CAV2 promotes the growth of renal cell carcinoma through the EGFR/PI3K/Akt
      pathway.
AB  - Background: Caveolin-2 (CAV2) is reported to have an important role in cancer.
      The following study investigated the expression and function of CAV2 in kidney
      cancer in vitro and in vivo. Materials and methods: Real-time PCR,
      immunohistochemistry and Western blotting analysis were used to determine CAV2,
      epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K) and
      protein kinase B (Akt) in kidney cancer cell line OS-RC-2 and clinical specimens.
      The role of CAV2 in maintaining kidney cancer malignant phenotype was examined by
      wound healing assay, Matrigel invasion assays and mouse orthotopic xenograft
      model. Results: Higher expression of CAV2 was found in renal cell carcinoma
      tissue compared to normal tissue. Furthermore, increased expression of CAV2 was
      associated with cancer progression. Also, silencing of CAV2 inhibited the
      proliferation, migration and invasion, as well as the expression of EGFR, PI3K
      and p-Akt in OS-RC-2 cells in vitro, and OS-RC-2 xenograft growth in vivo.
      Conclusion: Our results revealed that CAV2 promotes the growth of renal cell
      carcinoma through EGFR/PI3K/Akt pathway.

PMID- 30288055
TI  - SOX2, a stemness gene, induces progression of NSCLC A549 cells toward anchorage
      independent growth and chemoresistance to vinblastine.
AB  - Background: Non-small cell lung cancer (NSCLC) is difficult to treat
      successfully. This intractability is mainly due to the cancer progressing through
      invasion, metastasis, chemotherapeutic resistance and relapse. Stemness has been
      linked to the various steps of cancer progression in a variety of tumors, yet
      little is known regarding its role in NSCLC. Purpose: In this study, we sought to
      determine the role of SOX2, a master regulator of pluripotency, in the growth of
      extracellular matrix (ECM)-detached cells during cancer progression. Methods: We
      established a three-dimensional (3D) Poly-2-hydroxyethyl methacrylate (poly-HEMA)
      culture of lung adenocarcinoma (LUAD) A549 cells as an ECM-detached cell growth
      model and examined the role of stemness genes using siRNA and small molecule
      inhibitor in comparison to standard two dimensional (2D) culture. Results: In
      poly-HEMA culture, A549 cells formed substratum-detached spheroids with
      characteristics of intermediate epithelial to mesenchymal transition (EMT) and
      exhibited greater expression of SOX2 than did control 2D cells. Knockdown of SOX2
      markedly suppressed the growth of A549 cell aggregates in poly-HEMA culture
      conditions and furthermore increased their sensitivity to the anticancer drug
      vinblastine with concomitant downregulation of the activity of the anti-apoptotic
      AKT kinase. Interestingly, a small molecule, RepSox, which replaces SOX2,
      stimulated A549 cell growth in poly-HEMA 3D culture condition. Conclusion: Our
      findings strongly indicate that SOX2 contributes to anchorage-independent growth
      and chemoresistance via its downstream signaling mediator AKT kinase during the
      disease progression of NSCLC. SOX2 may therefore be an invaluable therapeutic
      target of NSCLC.

PMID- 30288057
TI  - MicroRNA-671-3p promotes proliferation and migration of glioma cells via
      targeting CKAP4.
AB  - Background and objective: Glioma is one of the most aggressive and malignant
      cancers originating from the human brain. Increasing evidence suggests that
      aberrant expression of microRNAs (miRNAs) frequently occurs in glioma and miRNAs
      are critical regulators of glioma. miR-671 has recently been revealed to be a
      novel miRNA that plays a vital role in human glioblastoma multiforme. However,
      the functional role and underlying mechanisms of miR-671-3p require further
      analysis. Materials and methods: Western blot and fluorescence quantitative PCR
      were used to assess the expression of cytoskeleton-associated protein 4 (CKAP4)
      and miR-671-3p, respectively. A Cell Counting Kit-8 (CCK-8) assay and a Boyden
      chamber assay were used to detect the proliferative and migratory abilities of
      glioma cells. A luciferase assay was used to determine the target gene of miR-671
      3p. Apoptosis was analyzed by flow cytometry. Results: Our results revealed that
      overexpression of miR-671-3p promoted cell proliferation and migration in vitro.
      Meanwhile, forced expression of miR-671-3p reduced apoptosis. In contrast,
      inhibition of miR-671-3p had the opposite effects. We also identified CKAP4 to be
      a direct target of miR-671-3p. The expression levels of CKAP4 were decreased in
      clinical samples and inversely correlated with miR-671-3p expression levels.
      Ectopic expression of CKAP4 reversed the promotive activity of miR-671-3p in the
      proliferation and migration and enhanced apoptosis. Conclusion: Our study
      demonstrates that miR-671-3p is a predominant positive regulator of glioma
      progression, thus providing new insights into the molecular mechanisms of glioma
      development. The findings suggest that the miR-6713p/CKAP4 axis may serve as a
      potential therapeutic target or biomarker in glioma.

PMID- 30288058
TI  - Mechanisms, monitoring, and management of tyrosine kinase inhibitors-associated
      cardiovascular toxicities.
AB  - The tyrosine kinase inhibitor (TKI) drug class is a prominently used option in
      the treatment of various cancers. Safety evaluation of these drugs has shown
      evidence of cardiotoxicity of varying frequency and severity between agents;
      concern has led to updated labeling, warning prescribers of such. This review
      seeks to clarify the present dangers and investigate cardiotoxic mechanisms of
      action for each discussed TKI. Dasatinib was connected primarily with an
      incidence of fluid retention, edema, QT prolongation, and pulmonary hypertension
      in clinical studies. It is theorized that this is due to a combination of off
      target kinase binding and on-target binding of Bcr-Abl, and less likely,
      mitochondrial induced apoptosis. Studies showed sorafenib to carry the risk of
      hypertension, QT prolongation, and myocardial infarction. Proposed mechanisms for
      these side effects include inhibition of proteins, vascular endothelium growth
      factor receptor, hERG potassium channels, and the RAF/MERK/ERK pro-survival
      pathway. Finally, lapatinib showed evidence of decreased left ventricular
      ejection fraction (LVEF) and QT prolongation in clinical studies. The literature
      attributes these as side effects of on-target ErbB2 binding leading to
      mitochondrial induced apoptosis. The concern warranted by these findings is in
      question. Pooled safety data suggest that the overall risk for cardiotoxicity is
      minimal in dasatinib and lapatinib. Sorafenib seems to carry a moderate concern.
      For the discussed agents, recommendations agree that routine monitoring via
      methods such as electroencephalogram, cardiac biomarkers, and blood pressure is
      warranted during the course of treatment, in addition to a comprehensive
      collection of past medical history and risk factors to identify those at
      heightened risk for cardiovascular events.

PMID- 30288059
TI  - PLK1 as a potential prognostic marker of gastric cancer through MEK-ERK pathway
      on PDTX models.
AB  - Background: PLK1 has been identified as having a great effect on cell division
      and maintaining genomic stability in mitosis, spindle assembly, and DNA damage
      response by current studies. Materials and methods: We assessed PLK1 expression
      in cervical cancer tissues and cells. We have also evaluated the effects of PLK1
      on gastric cancer cell proliferation, migration, and apoptosis both in vitro and
      in vivo. Results: Our results show that PLK1 is overexpressed in gastric cancer
      tissues and cells. Inhibition of PLK1 contributes cell cycle G2-phase arrest and
      inhibits the proliferation, migration, and apoptosis of gastric cancer (GC)
      cells, whereas its overexpression promotes proliferation, migration, and
      apoptosis in these cells. Moreover, PLK1 inhibition reduces expression of pMEK
      and pERK. More importantly, in vivo by analyzing tumorigenesis in patient-derived
      tumor xenograft (PDTX) models, the inhibition of PLK1 activity by BI6727
      significantly decreased the volume and weight of the tumors compared with control
      group (P<0.01). Conclusion: Our results found that PLK1 has a significant impact
      on the survival of GC cells; it may become a prognostic judge, a potential
      therapeutic target, and a preventative biomarker of GC.

PMID- 30288060
TI  - Overexpression of GPR35 confers drug resistance in NSCLC cells by beta
      arrestin/Akt signaling.
AB  - Background: Non-small-cell lung cancer (NSCLC) is the major leading cause of
      cancer-related death around the world. The resistance to chemotherapy limits the
      effects of clinical treatment. The aim of this study was to identify novel
      mechanisms involved in NSCLC chemoresistance. Materials and methods: We explored
      the public database and commercial tissue microarray to evaluate the expression
      of G protein-coupled receptor 35 (GPR35). We established the chemoresistant A549
      cell line to further investigate the biological function of GPR35 in vitro and in
      vivo. Then, we measured the altered signalings that GPR35 knocking down by
      Western blot assay. Results: We demonstrated that GPR35 expression was
      significantly elevated in NSCLC tissues and correlated with poor prognosis. GPR35
      was upregulated in our in vitro chemoresistance cell model. GPR35 depletion
      reduced the half maximal inhibitory concentration of chemodrugs and restored the
      sensitivity both in vitro and in vivo. Mechanically, we found that GPR35-mediated
      chemoresistance occurred partially via beta-arrestin-2/Akt signaling.
      Furthermore, inhibition of beta-arrestin-2 or Akt activation could suppress the
      GPR35 expression and overcome chemoresistance. Conclusion: Our results suggested
      that GPR35 might serve as a novel therapeutic target to enhance the chemotherapy
      efficacy in NSCLC.

PMID- 30288061
TI  - Effect of long non-coding RNA AOC4P on gastrointestinal stromal tumor cells.
AB  - Objective: In this research, we explored the effect of long non-coding RNA
      (lncRNA) AOC4P on gastrointestinal stromal tumor (GIST) cells. Materials and
      methods: The expression of lncRNA AOC4P in tissues was detected by real-time PCR
      (RT-PCR). The epithelial-mesenchymal transition (EMT)-related proteins in tissues
      were analyzed by Western blot. The experiment included negative control group
      (CN), silence AOC4P group (si AOC4P), and silence negative control group (si CT).
      RT-PCR, MTT, Scratch, Transwell, and Annexin V-FITC methods were used to detect
      the expression of lncRNA AOC4P, cell proliferation, cell migration ability, cell
      invasion ability, and apoptosis, respectively. The EMT-related proteins including
      TGF-beta, ZEB1, Vimentin, Snail, and E-cadherin were analyzed by Western blot.
      Results: The expression of lncRNA AOC4P and the expression of EMT-related
      proteins in high-risk GISTs were higher than that in low- and intermediate-risk
      GISTs (P<0.05). It was revealed that cell proliferative migration and invasive
      ability in si AOC4P group was decreased than that in CN and si CT groups
      (P<0.05), and cell apoptosis in si AOC4P group was higher than that in si CT
      group. The results of Western blot demonstrated that the expression of TGF-beta1,
      ZEB1, Vimentin, and Snail in si AOC4P group were lower than that in si CT and CN
      group (P<0.05), and the expression of E-cadherin in si AOC4P group was higher
      than that in si CT and CN group (P<0.05).

PMID- 30288062
TI  - Erratum: Efficient removal of hospital pathogens from hard surfaces by a combined
      use of bacteriophages and probiotics: potential as sanitizing agents
      [Corrigendum].
AB  - [This corrects the article on p. 1015 in vol. 11, PMID: 30104889.].

PMID- 30288064
TI  - Trichosporon dohaense, a rare pathogen of human invasive infections, and
      literature review.
AB  - Background: Trichosporon dohaense is a rare fungal species that has not been
      described in human invasive infections. Patients and methods: In this study, we
      investigated two T. dohaense isolates from patients with invasive infections in
      two hospitals in China, as part of the China Hospital Invasive Fungal
      Surveillance Net (CHIF-NET) program. Both patients were under immunocompromised
      conditions. Results: On chromogenic agar, T. dohaense isolates were dark blue,
      similar to the color of Candida. tropicalis, but the characteristic moist colony
      appearance was quite different from that of T. asahii. The two isolates were
      misidentified as T. asahii and T. inkin by the VITEK 2 YST system. The rDNA
      internal transcribed spacer (ITS) region and the D1/D2 domain sequences of the
      two T. dohaense isolates were 100% identical to T. dohaense type strain
      CBS10761T. The sequence of the intergenic spacer region-1 also clearly
      distinguished the species. Of the three matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry systems, Bruker Biotyper
      and Autobio MS correctly identified the two isolates to species level, whereas
      Vitek MS systems misidentified them as T. ovoides or T. asteroides. Echinocandins
      exhibited no in vitro activities against the two T. dohaense isolates. In
      addition, the isolates exhibited intermediate susceptibility to fluconazole (with
      minimal inhibitory concentrations [MICs] of 8 and 16 ug/mL) and itraconazole,
      voriconazole, and posaconazole (MICs of 0.25-1 ug/mL). T. dohaense demonstrated
      susceptibility to amphotericin B with MIC of 1 ug/mL. The MICs of fluconazole and
      voriconazole in our study were higher than the MIC50 of 62 for T. asahii isolates
      (4 and 0.064 ug/mL) in the CHIF-NET program. Conclusion: This case study points
      to a possible emergence of T. dohaense as an opportunistic human invasive fungal
      pathogen, and the reduced susceptibility should be noted.

PMID- 30288065
TI  - Widespread amphotericin B-resistant strains of Aspergillus fumigatus in Hamilton,
      Canada.
AB  - Purpose: Amphotericin B (AMB) is one of the major antifungal drugs used in the
      management of aspergillosis and is especially recommended for treating triazole
      resistant strains of Aspergillus fumigatus. However, relatively little is known
      about the AMB susceptibility patterns of A. fumigatus in many parts of the world.
      This study aims to describe the AMB susceptibility patterns in Hamilton, Ontario,
      Canada. Methods: The in vitro susceptibilities of 195 environmental and clinical
      A. fumigatus isolates to AMB were tested by the broth microdilution method as per
      the Clinical and Laboratory Standards Institute's guidelines. Catalase-generated
      oxygen bubbles trapped by Triton X-100 were used to quantify catalase activity in
      a representative group of isolates. Results: Of the 195 isolates, 188 (96.4%) had
      the minimum inhibitory concentration (MIC) of AMB >=2 mg/L, with approximately
      80% and 20% of all clinical and environmental isolates having MICs of >= 4 mg/L.
      Overall, the clinical isolates were less susceptible to AMB than environmental
      isolates (P-value <0.001). The strain with the highest AMB MIC (16 mg/L) had one
      of the highest catalase activities. However, there was no correlation between AMB
      MIC and catalase activity in our sample. Conclusion: The widespread AMB
      resistance suggests that using AMB in the management of A. fumigatus infections
      in Hamilton would likely result in treatment failure. Although high catalase
      activity may have contributed to AMB resistance in some isolates, the
      mechanism(s) for the observed AMB resistance in Hamilton is unknown and likely
      complex.

PMID- 30288063
TI  - Characterization of antimicrobial resistance mechanisms in carbapenem-resistant
      Pseudomonas aeruginosa carrying IMP variants recovered from a Mexican Hospital.
AB  - Purpose: Pseudomonas aeruginosa infections in hospitals constitute an important
      problem due to the increasing multidrug resistance (MDR) and carbapenems
      resistance. The knowledge of resistance mechanisms in Pseudomonas strains is an
      important issue for an adequate antimicrobial treatment. Therefore, the objective
      was to investigate other antimicrobial resistance mechanisms in MDR P. aeruginosa
      strains carrying bla IMP, make a partial plasmids characterization, and determine
      if modifications in oprD gene affect the expression of the OprD protein.
      Methodology: Susceptibility testing was performed by Kirby Bauer and by Minimum
      Inhibitory Concentration (presence/absence of efflux pump inhibitor); molecular
      typing by Pulsed-field gel electrophoresis (PFGE), resistance genotyping and
      integrons by PCR and sequencing; OprD expression by Western blot; plasmid
      characterization by MOB Typing Technique, molecular size by PFGE-S1; and bla IMP
      location by Southern blot. Results: Among the 59 studied P. aeruginosa isolates,
      41 multidrug resistance and carbapenems resistance isolates were detected and
      classified in 38 different PFGE patterns. Thirteen strains carried bla IMP; 16
      bla GES and four carried both genes. This study centered on the 17 strains har
      boring bla IMP. New variants of beta-lactamases were identified (bla GES-32, bla
      IMP-56, bla IMP-62) inside of new arrangements of class 1 integrons. The presence
      of bla IMP gene was detected in two plasmids in the same strain. The
      participation of the OprD protein and efflux pumps in the resistance to
      carbapenems and quinolones is shown. No expression of the porin OprD due to stop
      codon or IS in the gene was found. Conclusions: This study shows the
      participation of different resistance mechanisms, which are reflected in the
      levels of MIC to carbapenems. This is the first report of the presence of three
      new variants of beta-lactamases inside of new arrangements of class 1 integrons,
      as well as the presence of two plasmids carrying bla IMP in the same P.
      aeruginosa strain isolated in a Mexican hospital.

PMID- 30288066
TI  - Effects of oral probiotic supplementation on gut Lactobacillus and
      Bifidobacterium populations and the clinical status of low-birth-weight preterm
      neonates: a multicenter randomized, double-blind, placebo-controlled trial.
AB  - Aim: Probiotic bacteria administered directly after birth to preterm neonates may
      improve gastrointestinal function and may reduce the incidence of late-onset
      sepsis, which is a frequent complication in this group. Purpose: The main
      objective of this study was to evaluate whether a new probiotic bacterial mixture
      of Lactobacillus rhamnosus KL53A and Bifidobacterium breve PB04 given to preterm,
      low-birth-weight neonates would influence composition of their gut microbiota and
      sepsis rates. Patients and methods: This study was a multicenter, randomized,
      double-blind, placebo-controlled trial conducted in clinical centers of neonatal
      care in Poland. A probiotic or placebo preparation was given twice daily to 181
      preterm low-birth-weight neonates who were eligible for enteral feeding between
      July 2012 and July 2013. The probiotic was given to 90 neonates, while placebo
      was given to 91 neonates. The gut microbiota was monitored by microbiological
      analysis of stool samples. Sepsis episodes were detected on the basis of clinical
      and laboratory findings and confirmed by blood cultures. Results: Tested
      probiotic administration resulted in continuous increase of the Lactobacillus and
      Bifidobacterium counts in the gut microbiota. The applied tested strains
      successfully colonized the neonates gut since they were present in over 90% of
      stool samples, which was confirmed by molecular analysis. Regardless of the study
      group (probiotic or placebo), B. breve colonization correlated with lower
      staphylococcal sepsis incidence, which was irrespective of whether probiotics
      were given. No sepsis case caused by strains included in study probiotic was
      recorded. Conclusion: Appropriately selected and characterized probiotic bacteria
      may be safely given to preterm neonates to normalize their distorted gut
      microbiota and may contribute to lower staphylococcal sepsis rates.

PMID- 30288067
TI  - Evaluation of blood culture broths with lysis buffer to directly identify
      specific pathogens by matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry methods.
AB  - Background: Matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) is now widely used to detect pathogens in clinical
      settings in Japan. Method: Here, we report the effects of adding lysis buffer in
      the MALDI-TOF MS method to directly detect bacteria from 3 blood culture systems
      and compare their detection efficiencies for each pathogen. Results: Blood
      culture broths from BD, bioMerieux, and Oxoid showed similar detection
      efficiencies without lysis buffer use and Escherichia coli, Klebsiella
      pneumoniae, and Pseudomonas aeruginosa were efficiently detected in all broths
      when lysis buffer was used. However, Streptococcus pneumoniae was not detected in
      BD broth when lysis buffer was added. Furthermore, Haemophilus influenzae and
      Bacteroides fragilis were not detected in all 3 systems when lysis buffer was
      used. Conclusion: Optimization of blood culture system and lysis buffer is
      necessary according to each pathogen for direct identification by MALDI-TOF MS
      methods.

PMID- 30288069
TI  - Cost-effectiveness analysis of treatment timing considering the future entry of
      lower-cost generics for hepatitis C.
AB  - Background: Cost-benefit analyses are crucial to inform treatment policies,
      particularly when the cost of patented drugs is very high. The cost of patented
      drugs is the limiting factor in hepatitis C treatment. However, hepatitis C drug
      costs are expected to fall following patent expiration, due to generic drug
      introduction. Methods: An existing mathematical model by Shih et al was extended
      to consider lower-cost future generics in health economic models of hepatitis C.
      The model compared the cost-effectiveness of treating patients now with patented
      drugs vs postponing treatment until after patent expiration. Results: For
      ledipasvir-sofosbuvir, this study finds that it is almost always more cost
      effective to treat hepatitis C with high-cost patented drugs immediately rather
      than waiting for patent expiry. For ledipasvir-sofosbuvir, a generic would need
      to enter the market at <16.40% of the patented price for delayed treatment to be
      cost effective. The further that patent expiry is in the future, the more cost
      effective delayed treatment becomes; however, uncertainty about generic pricing
      and market entry times are also higher if patent expiry is in the distant future.
      Conclusion: It is more cost effective to treat hepatitis C sooner rather than
      later, regardless of the stage of the disease, and despite the high cost of
      patented drugs. However, patented drugs are being produced globally for prices
      much lower than those seen in the UK. Therefore, negotiation of patented drug
      prices with pharmaceutical companies may be a crucial step in cost effective
      treatment of hepatitis C.

PMID- 30288068
TI  - Phenotypic and genotypic drug sensitivity of Mycobacterium tuberculosis complex
      isolated from South Omo Zone, Southern Ethiopia.
AB  - Background: Knowledge of drug-sensitivity patterns of Mycobacterium tuberculosis
      complex (MTBC) strains isolated from patients is an important aspect of TB
      control strategy. This study was conducted to evaluate the drug sensitivity of
      MTBC isolates in South Omo, southern Ethiopia. Materials and methods: A total of
      161 MTBC isolates (153 from new cases and eight re-treatment TB cases) were
      isolated using Lowenstein Jensen medium of which 126 isolates were able to be
      tested for drug sensitivity by BACTECTMMGITTM 960 system, while all the 161
      isolates were tested by GenoType(r) MTBDRplus VER 2.0. Descriptive statistics and
      logistic regression were used to express and present results. Results: On the
      basis of MGIT 960 system, the prevalence of mono-resistance was 9.2% (11/119) in
      the new cases, although neither poly-resistance nor multidrug resistance (MDR)
      was recorded in these cases. On the basis of GenoType MTBDRplus assay, two of the
      153 isolates (1.3%) of the new cases were mono-resistant for rifampicin (RIF) and
      one of these isolates had known rpoB gene mutation (H526D). One of the eight
      (12.5%) isolates obtained from the re-treatment cases was MDR with rpoB gene
      mutation (D516V) and katG gene mutation (S315T2). Taking MGIT 960 system as a
      gold standard, the sensitivities of the MTBDRplus assay were 33.3%, 100% and 100%
      for detection of resistance to isoniazid, RIF and MDR, respectively. On the other
      hand, its specificities were 99.2%, 100% and 100% for detection of resistance to
      RIF, isoniazid and MDR, respectively. Conclusion: The magnitude of drug
      resistance was relatively low in the new TB cases of South Omo as compared to the
      reports from the other regions of the country. This is encouraging and hence the
      TB Control Program in the Zone should strengthen its program so that the
      emergence of drug resistance is inhibited.

PMID- 30288070
TI  - Impact of a pharmacist-led diabetes management on outcomes, utilization, and
      cost.
AB  - Purpose: Pharmacist-led medication therapy disease management (MTDM) has shown
      improvement in clinical outcomes in patients with certain chronic diseases.
      However, only limited data demonstrating the impact on health care utilization
      and cost of care are available. This study seeks to evaluate the impact of a
      pharmacist-led MTDM program on clinical surrogate outcomes, care utilization, and
      cost of care among patients with diabetes mellitus. Methods: A retrospective
      cohort study was conducted by utilizing electronic health records and insurance
      claims data. Patients were identified between February 2011 and December 2014.
      Data were collected from Geisinger, a large integrated health care system located
      in Pennsylvania and southern New Jersey. A total of 5,500 patients with diabetes
      mellitus were identified; 2,750 were enrolled in MTDM and were 1-to-1 propensity
      score-matched to a comparison cohort not enrolled in a pharmacist-led MTDM
      program. Results: There were no differences between groups in composite HbA1c,
      blood pressure, or low-density lipoprotein cholesterol goal attainment at 12
      months (12% vs 12%, P=0.53). HbA1c goal was reached more frequently among
      patients without MTDM compared to those at 12 months (57% vs 51%, P<0.0001).
      There were no significant differences between the two cohorts in the attainment
      of blood pressure or low-density lipoprotein cholesterol goals at 12 months. MTDM
      was associated with reduced all-cause hospitalization rate (-19.6%; P=0.02) as
      well as increased primary care physician visits (18.5%; P<0.001) and lower
      average per-member-per-month medical cost (-13%, P=0.027). Conclusion: Despite
      the lack of impact on the clinical surrogate outcomes, MTDM was associated with
      lower cost of care and fewer hospitalizations, possibly facilitated by increased
      monitoring (ie, higher primary care utilization).

PMID- 30288071
TI  - Alterations in the gene expression of drug and arachidonic acid-metabolizing
      Cyp450 in the livers of controlled and uncontrolled insulin-dependent diabetic
      mice.
AB  - Background: Diabetic patients have lower capacity to metabolize drugs in
      comparison to normal people. Therefore, the present study aimed to investigate
      the alterations in gene expression of drug and arachidonic acid metabolizing
      cytochrome p450s (cyp450s) in the livers of controlled (CDM) and uncontrolled
      (UDM) insulin-dependent diabetic mice. Methods: Balb/c mice were treated with
      single dose of streptozocin (240 mg/kg) to induce diabetes and compared with
      control group, which was treated with citric buffer (pH =4.5). After 3 days, the
      blood glucose level was measured to confirm the induction of diabetes.
      Normalization of blood glucose level in diabetic mice was achieved after 0.1
      mL/kg Mixtard(r) insulin therapy for more 5 days. Then, the mice livers were
      isolated to extract RNA and convert it to cDNA. The gene expression of 14 genes,
      which play a major role in drug and arachidonic acid metabolism, were measured
      using quantitative real-time polymerase chain reaction technique. Results: It was
      found that the gene expression was downregulated (ANOVA test, P-value <0.05) in
      the livers of UDM mice. The most downregulated genes were cyp4a12, cyp1a2, and
      slc22a1 with more than 10-fold reduction. The livers of CDM mice showed
      significantly (P-value <0.05) higher levels of mRNA than UDM mice, but still
      lower than the non-diabetic mice. Conclusion: This study concluded that hepatic
      gene expression of drug metabolizing and arachidonic acid- cyp450 enzymes is
      reduced in insulin-dependent diabetic mice, which can explain, at least in part,
      the variation in drug and fatty acid metabolism between normal and diabetic
      patients.

PMID- 30288072
TI  - Assessment of sleep quality and its predictors among patients with diabetes in
      Jazan, Saudi Arabia.
AB  - Background: Poor sleep quality is common among patients with diabetes. It is
      associated with negative physical, psychological, and functional consequences.
      However, the implicated risk factors of poor sleep quality remain uncertain.
      Objectives: This study aimed to determine the prevalence of poor sleep quality
      among patients with diabetes and to investigate the factors associated with the
      poor sleep quality. Patients and methods: An analytical cross-sectional study of
      307 diabetic patients in Jazan, Saudi Arabia was conducted in 2018. A multistage
      cluster random sampling was used to select the study participants. Sleep quality
      was assessed using the Pittsburgh Sleep Quality Index (PSQI). Data on patient's
      characteristics were gathered via patients' interviews, and medical data were
      collected based on the patients' files. Logistic regression analysis was used to
      identify the predictors of poor sleep quality. Results: The mean score of PSQI
      was 5.29+/-2.73. The prevalence of poor sleep quality was 55.4% (95% CI 49.7
      60.8). Sociodemographic and clinical factors were significantly associated with
      poor sleep quality, such as being elderly, female, illiterate, smoker,
      complications of diabetes, comorbidity, or psychological symptoms. However,
      female gender was the strongest predictor of reporting poor quality of sleep, OR=
      3.69, 95% CI 1.65-8.28 (P<0.001). Conclusion: Poor sleep quality among diabetic
      patients is a prevalent health problem. Many factors can affect sleep quality.
      Health care providers may consider routine screening for and address sleep
      problems among diabetic patients.

PMID- 30288073
TI  - Obesity and nonalcoholic fatty liver disease: current perspectives.
AB  - Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common
      cause of chronic liver disease due to an increase in the prevalence of obesity.
      The development of NASH leads to an increase in morbidity and mortality. While
      the first line of treatment is lifestyle modifications, including dietary changes
      and increased physical activity, there are no approved pharmacological treatment
      agents for NAFLD and NASH currently. Due to its complex pathophysiology,
      different pathways are under investigation for drug development with the focus on
      metabolic pathways, inflammation, and slowing or reversing fibrosis. There are
      several agents advancing in clinical trials, and promising results have been seen
      with drugs that affect hepatic steatosis, inflammation, and fibrosis. This review
      will provide an overview on NAFLD and some of the mechanisms of disease that are
      being targeted with pharmacologic agents.

PMID- 30288074
TI  - Developmental origins of health and disease: a new approach for the
      identification of adults who suffered undernutrition in early life.
AB  - Background: Undernutrition in early life (UELife) is a condition associated with
      greater occurrence of chronic diseases in adulthood. Some studies on this
      relationship have used short stature as indicator of UELife. However, other non
      nutritional factors can also determine short stature. Depending on the severity
      of UELife, the human body reacts primarily compromising weight and length gain,
      but prioritizing brain growth, resulting in disproportionate individuals. Based
      on this premise, this study aimed to validate a new anthropometric indicator of
      UELife. Design: Using stature and head circumference data from a probabilistic
      sample of 3,109 women, the Head-to-Height Index was calculated: HHI = (head *
      2.898)/height. A HHI >1.028 (75th percentile) was the best cutoff for predicting
      obesity (best balance between sensitivity/ specificity, largest area under the
      receiver operating characteristic curve, and highest correlation coefficient) and
      was used to define the condition of body disproportionality. The strength of
      associations with several outcomes was tested for both disproportionality and
      short stature (height <=25th percentile: 153.1 cm). Results: In adjusted analysis
      for confounding factors (age, smoking, and education level), the strength of the
      associations between body disproportionality and the analyzed outcomes was
      greater than that observed when short stature was used. Respectively, the
      observed prevalence ratios (95% CI) were (P<0.05 for all comparisons): obesity:
      2.61 (2.17-3.15) vs 1.09 (0.92-1.28); abdominal obesity: 2.11 (1.86-2.40) vs 1.42
      (1.27- 1.59); high blood pressure: 1.24 (1.02-1.50) vs 0.90 (0.75-1.08);
      hypercholesterolemia: 2.98 (1.47-6.05) vs 1.65 (0.91-2.99); and
      hypertriglyceridemia: 1.47 (1.07-2.03) vs 0.91 (0.69-1.21). Conclusion: Body
      disproportionality is a more accurate indicator of UELife than short stature.
      While short stature may be genetically determined, a high HHI is due to metabolic
      adaptations to undernutrition in early life.

PMID- 30288075
TI  - Beyond photoaging: additional factors involved in the process of skin aging.
AB  - Studies assessing the impact of extrinsic factors on skin aging have increased
      during the last with the increase in life expectancy. Although most of the
      studies are about the sun radiation impact, many factors should be considered in
      elderly people, beyond environmental conditions. Lifestyle factors, like diet,
      sleeping, smoking, should be analyzed carefully, as common age-related conditions
      (menopause, diabetes, pulmonary diseases, etc.). All these factors could
      accelerate the natural decline of skin structure and functions, possibly
      affecting the responses to treatments and drugs. This review demonstrates that
      growing evidence regarding environmental factors that are associated with
      lifestyle and comorbidities deserve greater attention from researchers and
      dermatologists and may require new approaches in the management of skin aging.

PMID- 30288078
TI  - Inflammatory gene mRNA expression in human peripheral blood and its association
      with colorectal cancer.
AB  - Objective: The present study planned to investigate the changes in the mRNA
      expression of inflammatory genes and their association with colorectal cancer
      (CRC). Our findings could be useful for noninvasive early screening of CRC
      patients. Patients and methods: Venous blood of 20 CRC cases and 15 healthy
      controls was collected. The mRNA expression of COX-2, TNF-alpha, NF-kappaB and IL
      6 genes was carried out by using real-time polymerase chain reaction. Relative
      quantification was done to find out the fold change of these genes. Results: The
      mean age of cases and controls was 55 and 50 years, respectively. The DeltaCt of
      COX-2, TNF-alpha, NF-kappaB and IL-6 genes was significantly (p < 0.05) lower in
      cases as compared to controls. Subsequently, the mRNA expression of these genes
      was, respectively, 3.56-, 3.4-, 1.71- and 3.86-fold higher in CRC cases as
      compared to controls. Positive correlation of DeltaCt of COX-2 was found with
      DeltaCt of TNF-alpha (r = 0.461, p = 0.041) and NF-kappaB (r = 0.536, p = 0.015)
      in CRC cases. The mRNA expression of COX-2 was significantly lower in T2 stage,
      while mRNA expression of NF-kappaB was significantly lower in both T2 and T3
      stages of CRC as compared to T4 stage. Conclusion: The increased mRNA expression
      of COX-2 along with the high mRNA expression of TNF-alpha, NF-kappaB and IL-6
      genes may be associative risk factors for CRC. COX-2 and NF-kappaB genes were
      more expressed in advanced stages of CRC indicating their role in tumor
      progression. Our findings support the possible role of blood biomarker in the
      screening of CRC patients in the early stages.

PMID- 30288076
TI  - Short-course therapy for diarrhea-predominant irritable bowel syndrome:
      understanding the mechanism, impact on gut microbiota, and safety and
      tolerability of rifaximin.
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder
      characterized by abdominal pain that occurs with defecation or alterations in
      bowel habits. Further classification is based on the predominant bowel habit:
      constipation-predominant IBS, diarrhea-predominant IBS (IBS-D), or mixed IBS. The
      pathogenesis of IBS is unclear and is considered multifactorial in nature. GI
      dysbiosis, thought to play a role in IBS pathophysiology, has been observed in
      patients with IBS. Alterations in the gut microbiota are observed in patients
      with small intestinal bacterial overgrowth, and overgrowth may occur in a subset
      of patients with IBS. The management of IBS includes therapies targeting the
      putative factors involved in the pathogenesis of the condition. However, many of
      these interventions (eg, eluxadoline and alosetron) require long-term, daily
      administration and have important safety considerations. Agents thought to
      modulate the gut microbiota (eg, antibiotics and probiotics) have shown potential
      benefits in clinical studies. However, conventional antibiotics (eg, neomycin)
      are associated with several adverse events and/or the risk of bacterial
      antibiotic resistance, and probiotics lack uniformity in composition and
      consistency of response in patients. Rifaximin, a nonsystemic antibiotic
      administered as a 2-week course of therapy, has been shown to be safe and
      efficacious for the treatment of IBS-D. Rifaximin exhibits a favorable benefit-to
      harm ratio when compared with daily therapies for IBS-D (eg, alosetron and
      tricyclic antidepressants), and rifaximin was not associated with the emergence
      of bacterial antibiotic resistance. Thus, short-course therapy with rifaximin is
      an appropriate treatment option for IBS-D.

PMID- 30288077
TI  - The role of inflammation in irritable bowel syndrome (IBS).
AB  - Irritable bowel syndrome (IBS) is a complex, functional gastrointestinal disorder
      characterized by chronic abdominal pain or discomfort and altered bowel habits.
      Despite the global prevalence and disease burden of IBS, its underlying
      pathophysiology remains unclear. Inflammation may play a pathogenic role in IBS.
      Studies have highlighted the persistence of mucosal inflammation at the
      microscopic and molecular level in IBS, with increased recruitment of
      enteroendocrine cells. Substantial overlaps between IBS and inflammatory bowel
      disease have also been reported. This review thus aimed to discuss the body of
      evidence pertaining to the presence of mucosal inflammation in IBS, its putative
      role in the disease process of IBS, and its clinical relevance. Increased mast
      cell density and activity in the gut may correlate with symptoms of visceral
      hypersensitivity. As evidenced by patients who develop postinfectious IBS,
      infective gastroenteritis could cause systemic inflammation and altered
      microbiome diversity, which in turn perpetuates a cycle of chronic, low-grade,
      subclinical inflammation. Apart from mucosal inflammation, neuroinflammation is
      probably involved in the pathophysiology of IBS via the "gut-brain" axis,
      resulting in altered neuroendocrine pathways and glucocorticoid receptor genes.
      This gives rise to an overall proinflammatory phenotype and dysregulated
      hypothalamic-pituitary-adrenal axis and serotonergic (5-HT) functioning, which
      could, at least in part, account for the symptoms of IBS. Although a definite and
      reproducible pattern of immune response has yet to be recognized, further
      research into anti-inflammatories may be of clinical value.

PMID- 30288080
TI  - Clinical value of a serum anti-PLA2R antibody in the diagnosis and monitoring of
      primary membranous nephropathy in adults.
AB  - Objective: To compare the positive rate of anti-PLA2R antibodies in patients with
      primary membranous nephropathy (PMN), secondary membranous nephropathy (SMN), and
      non-membrane nephropathy (non-MN); evaluate serum anti-PLA2R antibodies in the
      diagnosis of PMN; quantify the serum anti-PLA2R antibody levels during the
      treatment of PMN patients; and evaluate the clinical value of monitoring changes
      in serum anti-PLA2R antibody quantification levels. Methods: The kidney tissue
      was collected by kidney biopsy. The expression of PLA2R in glomeruli was detected
      by immunofluorescence, and ELISA was used to quantify the serum anti-PLA2R
      antibody. The positive rate of PLA2R expression in renal tissue and positive rate
      of the anti-PLA2R antibody in the three groups were compared and calculated using
      a statistical method. The specificity and coincidence rate of anti-PLA2R used in
      the differential diagnosis of PMN and SMN were evaluated. The clinical value of
      monitoring changes in serum anti-PLA2R antibody quantification levels was
      evaluated. Result: The serum levels of the anti-PLA2R antibody were significantly
      higher in patients with PMN than in patients with SMN and non-MN group. The
      difference was statistically significant (P<0.05). The serum anti-PLA2R antibody
      became negative in the complete remission group. The serum anti-PLA2R antibody
      levels were significantly lower than before treatment in the partial remission
      group, and the difference was statistically significant (P<0.05). However, in the
      non-remission group, the serum anti-PLA2R antibody levels remained high.
      Conclusion: Detection of the serum anti-PLA2R antibody has a high specificity for
      diagnosing PMN. The change of the serum anti-PLA2R antibody level is closely
      related to the status of the PMN: if the anti-PLA2R antibody level has decreased,
      it indicates that the condition has improved; and if the serum anti-PLA2R
      antibody continues to show high levels of positive or quantitative increase, the
      condition is not in remission or has relapsed.

PMID- 30288081
TI  - Renal replacement therapy in patients with acute respiratory distress syndrome: a
      single-center retrospective study.
AB  - Background: Patients with acute respiratory distress syndrome (ARDS) who develop
      acute kidney injury have increased mortality and frequently require renal
      replacement therapy (RRT). The optimal timing for initiation of RRT after onset
      of ARDS to improve survival is not known. Methods: We retrospectively reviewed
      clinical data on patients admitted to our health system over a 2-year period.
      Individual charts were carefully reviewed to ascertain that patients met the
      Berlin criteria for ARDS and to categorize RRT utilization. The Kaplan-Meier
      analysis was conducted to compare early (L48 hours postintubation) versus late
      (>48 hours postintubation) initiation of RRT. Associations between RRT initiation
      and mortality were evaluated using Cox proportional hazards regression. Results:
      A total of 75 patients were identified with ARDS, 95% of whom received RRT.
      Mortality of patients who required RRT was 56%. The main indications for RRT
      initiation were fluid overload (75%), metabolic acidosis (64%), and hyperkalemia
      (33%). The Kaplan-Meier analysis comparing early initiation of RRT to late
      initiation of RRT showed no survival benefit. Cox proportional hazard models
      testing the association between timing of RRT initiation with survival and
      adjusting for sex, race, ethnicity, and Acute Physiology and Chronic Health
      Evaluation II score did not reach statistical significance (HR=0.94, 95% CI=0.48
      1.86). Conclusion: Timing of RRT initiation was not associated with a survival
      benefit. Prospective study in the utilization and outcomes of RRT in ARDS could
      assist in optimizing its usage in this population.

PMID- 30288082
TI  - Effects of ABCB1 rs1045642 polymorphisms on the efficacy and safety of amlodipine
      therapy in Caucasian patients with stage I-II hypertension.
AB  - Purpose: The aim of this study was to determine the impact of ABCB1 (MDR1)
      rs1045642 polymorphisms on the efficacy and safety of amlodipine in Caucasian
      patients. Patients and methods: The 12-week study included 100 patients. Patients
      with the newly diagnosed stage I-II hypertension (HT) were recruited to complete
      genotyping of the rs1045642 single-nucleotide polymorphism (SNP). The study
      design did not include a control group. Before treatment, all patients either did
      not undergo antihypertensive treatment at all or did not receive regular
      antihypertensive therapy. The initial dose was 5 mg/day. Four office blood
      pressure measurements, two 24-hour noninvasive ambulatory blood pressure
      measurements, and questionnaires of Tsvetov were used to evaluate the efficacy
      and safety of amlodipine. Results and conclusion: The highest antihypertensive
      effect in combination with the lowest incidence of adverse reactions was observed
      in the TT group, while patients with the CC genotype showed a low
      antihypertensive effect and the highest incidence of adverse effects. Patients
      with the CC genotype presented with adverse effects predominantly in the form of
      edema. A total of 33 patients reached the target blood pressure (SBP <140 mmHg;
      DBP <90 mmHg): two patients with the CC genotype (12%); 18 patients with the CT
      genotype (34%); and 13 patients with the TT genotype (43%). The intergroup
      differences were: CC vs CT, P=0.02; CC vs TT, P=0.02; and CT vs TT, P=0.05. The
      results of this study indicate the potential of pharmacogenetic testing for
      rs1045642 SNP when prescribing amlodipine for the first time in Caucasian
      patients with stage I-II arterial HT.

PMID- 30288079
TI  - Spotlight on the NLRP3 inflammasome pathway.
AB  - Inflammation is triggered by a repertoire of receptors detecting infections and
      damages. Some of these receptors directly bind microbial ligands, while others
      recognize endogenous molecules exposed under stress conditions, including
      infections. Most of these receptors can be engaged by a relatively limited number
      of stimuli. Differently, NLRP3 acts as a broad sensor of cell homeostasis rupture
      and can be activated downstream of a plethora of stimuli. NLRP3 then assembles a
      multiprotein platform resulting in caspase-1 activation, which controls, by
      direct cleavage, the maturation of cytosolic pro-cytokines including pro
      interleukin-1beta. In addition, caspase-1 processes cytosolic gasdermin-D and
      unleashes its pore-forming N-terminal domain, leading to the release of mature
      cytosolic cytokines and alarmins, as well as pyroptotic cell lysis. Accumulating
      evidences of the aggravating role of NLRP3-mediated inflammation in various
      highly prevalent human conditions, including diabetes, neurodegenerative and
      cardiovascular diseases, raises a huge clinical interest. Nevertheless, the
      molecular mechanism governing NLRP3 activation remains insufficiently understood.
      In line with the detrimental consequences of NLRP3 activation illustrated by the
      aforementioned pathologies, this process is tightly regulated. In this review, we
      address the current understanding of the control of NLRP3 activity which can be
      divided into two coordinated processes referred to as priming and activation. In
      particular, we detail the emerging role of NLRP3 post-translational modifications
      critical in inflammasome assembly regulation.

PMID- 30288083
TI  - Mini-laparoscopic cholecystectomy with the MiniLap(r) percutaneous surgical
      system: a series of 32 patients.
AB  - Background: In recent years, mini-laparoscopic procedures are gaining the
      preference of most surgeons due to their potentially better surgical outcomes.
      The Mini Lap Percutaneous Surgical System with MiniGrip(r) Handle is currently
      the less invasive instrument and can be applied to a wide range of operations.
      The current paper presents its application on percutaneous laparoscopic
      cholecystectomy. Materials and methods: From January 2017 to June 2017, 32
      patients underwent percutaneous laparoscopic cholecystectomy with the MiniLap(r)
      system. All operations were performed by the same surgical team. Results: No
      conversions and no overall complications were reported. Drainage were not
      necessary. Mean surgical time was 35 minutes, while patients were released in <24
      hours after the operation. Conclusion: The MiniLap system with the use of the
      mini grip handle seems to sustain the benefits of performing laparoscopically.
      However, further trials should be conducted so as to establish its safety on
      cholecystectomies.

PMID- 30288084
TI  - Relapsing fever Borrelia in California: a pilot serological study.
AB  - Background: Borrelia spirochetes are tick-borne Gram-negative bacteria that cause
      disease in humans and animals. Although many studies have focused on Borrelia
      burgdorferi (Bb), the agent of Lyme disease, recent studies have examined the
      role of Relapsing Fever Borrelia (RFB) in human disease. In this pilot study, we
      have evaluated serological reactivity against Bb and RFB in patients residing in
      California. Methods: Serological testing for reactivity to Bb and RFB antigens
      was performed in 543 patients with suspected tick-borne illness using a Western
      blot technique. Further evaluation of a subset of 321 patients residing in
      California was obtained. Serum samples were tested for IgM and IgG antibodies
      reactive with Bb and RFB, and samples were classified by county of residence
      according to Bb reactivity alone, RFB reactivity alone, and dual reactivity
      against Bb and RFB. Seroreactivity was ranked in counties with the highest
      absolute number and the highest prevalence of positive samples. Results: Of the
      543 total serum samples, 32% were positive for Bb, 22% were positive for RFB, and
      7% were positive for both Bb and RFB. Of the 321 serum samples from patients
      residing in California, 33% were positive for Bb, 27% were positive for RFB, and
      11% were positive for both Bb and RFB. In the California cohort, the highest
      rates of positive serological testing for Bb were found in Santa Clara, Alameda,
      and Contra Costa counties, while the highest rates of positive serological
      testing for RFB were found in Santa Clara, Alameda, Marin, and San Francisco
      counties. The highest rates of dual reactivity against Bb and RFB were found in
      Contra Costa, Alameda, and San Francisco counties. Among the 24 counties with
      patients who were tested, Bb seropositivity alone was found in four counties, RFB
      seropositivity alone was found in two counties, and seropositivity for both Bb
      and RFB was found in 14 counties. Conclusion: Results of this pilot study suggest
      that seroreactivity against Bb and RFB is widespread in California, and dual
      exposure to Bb and RFB may complicate the diagnosis of tick-borne disease.
      Greater awareness of RFB and broader screening for this tick-borne infection is
      warranted.

PMID- 30288085
TI  - Pulsed radiofrequency of C2 dorsal root ganglion under ultrasound guidance for
      chronic migraine: a case report.
AB  - Chronic migraine is common but difficult to treat. Most patients respond poorly
      to drugs. Occipital nerve block such as stellate ganglion block is an effective
      treatment without continuous effect for migraine. Pulsed radiofrequency (PRF)
      technique has been shown to be effective in relieving headache and prolonging the
      effect of nerve block. This case report is about a patient who suffered from
      chronic migraine with occipital pain and was successfully treated with PRF of C2
      (axis) dorsal root ganglion (DRG) under ultrasound guidance confirmed by computed
      tomograpy scan. The patient did not feel headache after 1-year follow-up. This
      suggests that C2 DRG PRF might be considered as an alternative treatment for
      chronic migraine with occipital pain.

PMID- 30288086
TI  - Hypnosis intervention for the management of pain perception during cataract
      surgery.
AB  - Objective: To investigate the effectiveness of hypnosis in pain management during
      cataract surgery. Methods: Male or female patients with bilateral age-related
      cataract who wished to have both eyes subjected to phacoemulsification surgery
      were preliminarily admitted. Immediately after the first-eye surgery, each
      patient was evaluated for pain using the visual analog scale (VAS), and patients
      with a VAS score >1 were enrolled. By using block randomization, the enrolled
      patients were allocated to either the treatment group, which received a hypnosis
      intervention before the scheduled second-eye surgery, or the control group, which
      did not undergo hypnosis. The levels of anxiety, pain, and cooperation were
      evaluated independently by the patients and the surgeon. Results: During the
      intraoperative pain assessment, 5%, 34%, 38%, and 23% of patients in the control
      group reported experiencing no pain, mild pain, moderate pain, and severe pain,
      respectively. In contrast, in the hypnosis group, 18%, 56%, 15%, and 11% of
      patients reported experiencing no pain, mild pain, moderate pain, and severe
      pain, respectively, which showed significant differences between the groups
      (P<0.005). The evaluation of anxiety level showed that the mean score in the
      control group and hypnosis group was 11.77+/-0.32 and 6.64+/-0.21, respectively,
      revealing a highly significant difference between the two groups (P<0.005). The
      assessment of patient cooperation showed that only 5% and 18% of patients in the
      control group and 18% and 36% of patients in the hypnosis group showed excellent
      and good cooperation, respectively, while 47% of patients in the control group
      and only 24% of patients in the hypnosis group exhibited poor cooperation,
      revealing significant differences between the groups (P<0.005). Conclusion:
      Hypnosis may be considered as an auxiliary measure in cataract surgery,
      especially for patients who experienced obvious pain during the first-eye
      surgery.

PMID- 30288087
TI  - The polytrauma clinical triad in patients with chronic pain after motor vehicle
      collision.
AB  - Background: The polytrauma clinical triad (PCT) is a complex disorder composed of
      three comorbid diagnoses of chronic pain, post-traumatic stress disorder (PTSD),
      and postconcussion syndrome (PCS). PCT has been documented in veterans returning
      from deployment, but this is the first report on PCT prevalence in nonmilitary
      personnel after a motor vehicle collision (MVC). Methods: Data were drawn from
      routine intake assessments completed by 71 patients referred to a community-based
      clinic for chronic pain management. All patients completed the post-traumatic
      stress disorder checklist for the Diagnostic and Statistical Manual of Mental
      Disorders, fifth edition (PCL-5), and Rivermead Post-Concussion Symptoms
      Questionnaire (RPQ) during a standardized intake assessment. An additional
      modified RPQ score was derived to address previously reported symptom overlap
      between PCS and chronic pain. Results: Standard and modified RPQ scores yielded
      PCS prevalence rates of 100% and 54.9% in our sample, respectively. Results
      suggest that a modified RPQ score, limited to visual and vestibular symptoms, may
      be more useful PCS screening criteria in patients with chronic pain. PTSD
      screening criteria on the PCL-5 were met by 85.9% of the patients. More than half
      of the patients referred for chronic pain after MVC met criteria for PCT (52.1%).
      Patients who met PCT criteria reported worse headache, overall pain, and sleep
      quality outcomes. Conclusion: Among patients in our sample with chronic pain
      after MVC, more than half met criteria for PCT. A modified approach to RPQ
      scoring limited to visual and vestibular symptoms may be required to screen for
      PCS in these patients.

PMID- 30288089
TI  - Effects of whole-body electromyostimulation on chronic nonspecific low back pain
      in adults: a randomized controlled study.
AB  - Purpose: Low back pain (LBP) is one of the most frequent chronic conditions
      worldwide. Data from a recent meta-analysis indicated that whole-body
      electromyostimulation (WB-EMS), a time-effective, joint-friendly, and highly
      individualized training technology, demonstrated promising effects on LBP;
      however, methodologic limitations prevent definitive evidence for this result.
      Thus, the aim of this study was to conduct a randomized controlled WB-EMS trial
      to determine the corresponding effect on chronic, nonspecific LBP in people with
      chronic LBP. Patients and methods: Thirty LBP patients, 40-70 years old, were
      randomly assigned into two groups (WB-EMS: 15; control [CG]: 15). While the
      nonactive CG maintained their lifestyle, the WB-EMS group completed a 12-week WB
      EMS protocol (1*20 min/week) with slight movements, specifically dedicated to
      LBP. Pain intensity and frequency were determined by a 4-week pain diary before
      and during the last 4 weeks of intervention. Primary study endpoint was average
      pain intensity at the lumbar spine. Results: At baseline, no group differences
      apart from nonregular exercise were observed. Mean intensity of LBP decreased
      significantly in the WB-EMS group (P=0.002) and remained unchanged in the CG
      (P=0.730), with a significant difference between both groups (P=0.027). Maximum
      isometric trunk extensors improved significantly in the WB-EMS group (P=0.005),
      while no significant difference was seen in the CG (P=0.683). In contrast to the
      significant difference between WB-EMS group and CG for the latter parameter
      (P=0.038), no intergroup difference was determined for maximum isometric trunk
      flexors (P=0.091). The WB-EMS group showed a significant increase of this
      parameter (P=0.003), while no significant change was determined in the CG
      (P=0.563). Conclusion: WB-EMS is a time-effective training method for reducing
      chronic nonspecific LBP and increasing maximum trunk strength in people with such
      complaints. After this promising comparison with a nonactive CG, research needs
      to be extended to include comparisons with active groups (WB-Vibration,
      conventional back strengthening).

PMID- 30288090
TI  - Trends and patterns of analgesic prescribing in Malaysian public hospitals from
      2010 to 2016: tramadol predominately used.
AB  - Purpose: To examine the trends of analgesic prescribing at public tertiary
      hospital outpatient settings and explore the patterns of their utilization in
      nonsteroidal anti-inflammatory drugs (NSAIDs), tramadol, and opioid patients.
      Patients and methods: This cross-sectional study was conducted from 2010 to 2016
      using the prescription databases of two tertiary hospitals in Malaysia.
      Prescriptions for nine NSAIDs (ketoprofen, diclofenac, celecoxib, etoricoxib,
      ibuprofen, indomethacin, meloxicam, mefenamic acid, and naproxen), tramadol, and
      five other opioids (morphine, fentanyl, oxycodone, dihydrocodeine, and
      buprenorphine) were included in this study. Annual number of patients and
      prescriptions were measured in repeat cross-sectional estimates. Descriptive
      statistics and linear trend analysis were performed using Stata version 13.
      Results: A total of 192,747 analgesic prescriptions of the nine NSAIDs, tramadol,
      and five other opioids were given for 97,227 patients (51.8% NSAIDs patients,
      46.6% tramadol patients, and 1.7% opioid patients) from 2010 to 2016. Tramadol
      (37.9%, n=72,999) was the most frequently prescribed analgesic, followed by
      ketoprofen (17.5%, n=33,793), diclofenac (16.2%, n=31,180), celecoxib (12.2%,
      n=23,487), and other NSAIDs (<4.5%). All the analgesics were increased over time
      except meloxicam, indomethacin, and mefenamic acid. Opioids, primarily morphine
      (2.2%, n=4,021) and oxycodone (0.5%, n=1,049), were prescribed the least, but the
      rate of increase was the highest. Conclusion: Tramadol was the most frequently
      prescribed analgesic in hospital outpatient settings in Malaysia. Opioids were
      prescribed the least, but noted the highest increase in utilization.

PMID- 30288091
TI  - Beyond the muscular effects - onabotulinumtoxinA injections for pain control in
      chronic knee osteoarthritis: a case report.
AB  - We present a long-standing case of an 88-year-old woman with multiple
      comorbidities receiving intra-articular Botox(r) (onabotulinumtoxinA) injections
      for bilateral chronic knee osteoarthritis. She reported improved pain control and
      function supported by validated outcome measures.

PMID- 30288088
TI  - Nonsteroidal anti-inflammatory drugs in chronic pain: implications of new data
      for clinical practice.
AB  - COX2-selective and nonselective (ns) nonsteroidal anti-inflammatory drugs
      (NSAIDs) are widely used for chronic pain management. There are marked
      differences in the risk of adverse gastrointestinal (GI) and cardiovascular (CV)
      events among different NSAIDs. In 2017, publication of two randomized controlled
      trials and an individual patient-data meta-analysis provided robust data on the
      relative GI and CV tolerability profiles of currently available NSAIDs. The
      PRECISION study showed similar CV-event rates with celecoxib vs naproxen and
      ibuprofen, but GI tolerability was better for celecoxib. In the CONCERN study of
      high-GI-risk patients, celecoxib was associated with fewer adverse GI-tract
      events than naproxen. The meta-analysis showed no significant difference between
      celecoxib and ns-NSAIDs in the rate of acute myocardial infarction, and celecoxib
      was the only COX2-selective NSAID with a lower risk of adverse CV and GI events
      vs ns-NSAIDs. These data add to the body of knowledge about the relative
      tolerability of different NSAIDs and were used to propose an updated treatment
      algorithm. The decision about whether to use an NSAID and which one should be
      based on a patient's risk of developing adverse GI and CV events. Lower- and
      upper-GI-tract events need to be considered. Celecoxib has a better lower-GI
      tract tolerability profile than ns-NSAIDs plus a proton-pump inhibitor. In
      addition, the latest data suggest that long-term use of celecoxib 200 mg/day may
      be appropriate for patients at increased CV risk.

PMID- 30288092
TI  - Upregulation of the high-affinity choline transporter in colon relieves stress
      induced hyperalgesia.
AB  - Background: Irritable bowel syndrome (IBS) is a common disease with hyperalgesia,
      the mechanisms of which remain elusive. The cholinergic system is known to be
      involved in pain inhibitory pathways in multiple diseases, and its involvement in
      IBS is unknown. Objective: We aimed to determine whether high-affinity choline
      transporter CHT1, a major determinant of the cholinergic signaling capacity, is
      involved in regulating intestinal sensations associated with stress-induced
      visceral pain. Materials and methods: An IBS rat model was established by chronic
      water avoidance stress (WAS). Colonic pathologic alterations were detected by H&E
      staining. Visceral sensations were determined by scoring the abdominal withdrawal
      reflex (AWR) and visceromotor response (VMR) magnitude of the electromyogram in
      response to colorectal distension (CRD). Abdominal mechanical hyperalgesia was
      assessed by counting the number of withdrawal events evoked by applying von Frey
      filaments. Real-time PCR, Western blot, and immunostaining were performed to
      identify CHT1 expression in the colon. Acetylcholine (ACh) secretion was
      determined by ELISA. Effects of MKC-231, a choline uptake enhancer, on visceral
      pain were examined. Results: After 10 days of WAS exposure, AWR score and VMR
      magnitude in response to CRD were significantly enhanced and the number of
      withdrawal events was elevated. Protein and mRNA levels of CHT1 were considerably
      increased in the colon after WAS. CHT1 upregulation in the WAS-exposed group was
      largely abolished by ammonium pyrrolidinedithiocarbamate. The density of CHT1
      positive intramuscular cells and enteric neurons in the myenteric plexus was
      enhanced in WAS-exposed rats. Pharmacologic enhancement of CHT1 activity by MKC
      231 gavage could relieve the visceral pain of WAS rats by upregulating CHT1
      protein expression and enhancing ACh production. Conclusion: CHT1 may exert an
      antinociceptive effect in stress-induced visceral pain by modulating ACh
      synthesis through nuclear factor kappa B signaling. MKC-231 could be used as a
      potential drug to treat disorders with hyperalgesia.

PMID- 30288093
TI  - Erector spinae plane block for postoperative analgesia in laparoscopic
      cholecystectomy: a case report.
AB  - The Erector Spinae Plane Block (ESP) is a novel regional technique for anesthesia
      or analgesia. Originally the ESP block was described in 2016 in a case report
      regarding analgesia intervention for a case of thoracic neuropathic pain. Since
      then, there has been growing interest and research adding experience about the
      ESP block as regional anesthetic and analgesic technique. Reviewing the
      literature about this novel technique in databases like PubMed using the key
      words "erector spinae plane block" returns approximately 56 publications. So far
      there is no available big series of cases or reviews regarding the ESP block. The
      literature is limited to case reports or case series. With the present case we
      are interested in exploring the efficacy of ESP block as a postoperative
      analgesic method for laparoscopic cholecystectomy. We describe the case of a 76
      year-old female patient scheduled for laparoscopic cholecystectomy. Written
      informed consent was granted (for procedure and publication of photos). We
      applied a bilateral ultrasound-guided ESP block at T6 level while the patient was
      awake before general anesthesia induction. The anesthetic solution we used
      consisted of 12 mL Ropivacaine 0.375% plus 2 mg dexamethasone (on each side).
      After the successful administration of the block (observation of the solution
      spread between transverse process and the erector spinae muscles), general
      anesthesia was induced and the procedure was started. Procedure and recovery was
      uneventful with the patient experiencing very good analgesia (NRS pain score 0 up
      to 6 hours after block placement). The patient presented mild pain (NRS score of
      2-3) after 6 hours and requested the "on demand" pain medication (1 g paracetamol
      IV) only 10 hours after the ESP block (NRS pain score of 4-5). The patient
      experienced no nausea or vomiting, was mobilized easily about 6 hours after the
      block and was discharged the next day. This relatively simple and safe block
      dramatically reduced the amount of IV pain medication we usually administer for
      the specific procedure. The overall result was increased satisfaction of the
      patient and avoidance of opioid use.

PMID- 30288095
TI  - Analgesic efficacy, safety, and tolerability of a long-acting abuse-deterrent
      formulation of oxycodone for moderate-to-severe chronic low back pain in subjects
      successfully switched from immediate-release oxycodone.
AB  - Objectives: This post hoc analysis of data from a randomized, double-blind,
      placebo-controlled, enriched-enrollment randomized-withdrawal Phase III study
      evaluated the safety, tolerability, and analgesic efficacy of Oxycodone DETERx
      extended-release (ER), abuse-deterrent capsules (Xtampza(r) ER) in subjects with
      chronic low back pain who were successfully transitioned from immediate-release
      (IR) oxycodone. Methods: Continuous outcomes were analyzed using a mixed-model
      repeated-measures approach; binomial outcomes were analyzed using chi-squared;
      and time-to-event outcomes using Kaplan-Meier analyses. Results: A total of 110
      subjects previously prescribed IR oxycodone entered the Open-label Titration
      Phase. Forty-four subjects were randomized to Oxycodone DETERx (n=22) or placebo
      (n=22) in the 12-week Double-blind Maintenance Phase. Efficacy results in this
      subgroup showed a statistically significant difference between Oxycodone DETERx
      and placebo in average pain intensity scores from Randomization Baseline to Week
      12 (least squares mean [+/- standard error], -1.88 [0.70]; P=0.0078). Additional
      efficacy results indicated that Oxycodone DETERx vs placebo was associated with a
      statistically significant benefit in durability of effect from Week 2 through
      Week 12 (P<0.01), numbers of subjects with a >=30% (n [%] 10 [45.5%] vs 0 [0%];
      P=0.0004) and >=50% (10 [45.5%] vs 0 [0%]; P=0.0004) improvement in pain
      intensity, longer time-to-exit (P=0.0014), a greater number of subjects who
      completed the study (14 [63.6%] vs 4 [18.2%]), and less rescue medication use
      (acetaminophen; mean [SD], 163.5 [337.8] mg) vs 216.2 [377.3] mg). Adverse event
      profiles were consistent with opioid class effects and results from the original
      study; Oxycodone DETERx was well tolerated in subjects previously treated with
      short-acting oxycodone. Conclusions: Oxycodone DETERx resulted in clinically
      meaningful and statistically significant efficacy in subjects with chronic low
      back pain who were previously prescribed IR oxycodone and were successfully
      switched to ER Oxycodone DETERx.

PMID- 30288094
TI  - Correlation of changes in hemodynamic response as measured by cerebral optical
      spectrometry with subjective pain ratings in volunteers and patients: a
      prospective cohort study.
AB  - Purpose: Noninvasive cerebral optical spectrometry is a promising candidate
      technology for the objective assessment physiological changes during pain
      perception. This study's primary objective was to test if there was a significant
      correlation between the changes in physiological parameters as measured by a
      cerebral optical spectrometry-based algorithm (real-time objective pain
      assessment [ROPA]) and subjective pain ratings obtained from volunteers and
      laboring women. Secondary aims were performance assessment using linear
      regression and receiver operating curve (ROC) analysis. Patients and methods:
      Prospective cohort study performed in Human Pain Laboratory and Labor and
      Delivery Unit. After institutional review board approval, we evaluated ROPA in
      volunteers undergoing the cold pressor test and in laboring women before and
      after epidural or combined spinal epidural placement. Linear regression was
      performed to measure correlations. ROCs and corresponding areas under the ROCs
      (AUC), as well as Youden's indices, as a measure of diagnostic effectiveness,
      were calculated. Results: Correlations between numeric rating scale or visual
      analog scale and ROPA were significant for both volunteers and laboring women.
      AUCs for both volunteers and laboring women with numeric rating scale and visual
      analog scale subjective pain ratings as ground truth revealed at least good (AUC:
      70%-79%) to excellent (AUC >90%) distinction between clinically meaningful pain
      severity differentiations (no/mild-moderate-severe). Conclusion: Cerebral Optical
      Spectrometry-based ROPA significantly correlated with subjectively reported pain
      in volunteers and laboring women, and could be a useful monitor for clinical
      circumstances where direct assessment is not available, or to complement patient
      reported pain scores.

PMID- 30288096
TI  - Efficacy of preemptive analgesia on acute postoperative pain in children
      undergoing major orthopedic surgery of the lower extremities.
AB  - Background: Children undergoing major orthopedic surgery of the lower extremities
      can experience severe postoperative pain; yet, the ideal postoperative pain
      management strategy is unknown. Thus, in this patient population, we investigated
      the effect of intraoperative epidural infusion of local anesthetic on acute
      postoperative pain and analgesic consumption. Patients and methods: Patients
      (N=50, 3-12 years) randomly received either ropivacaine 0.15% (preemptive group)
      or normal saline (control group) as an initial bolus of 0.2 mL/kg, followed by
      continuous infusion of 0.15 mL/kg/h throughout surgery. Following surgery,
      patient-controlled epidural analgesia with ropivacaine 0.1% was provided. The
      main study outcomes were the revised Face, Legs, Activity, Cry, and Consolability
      pain scores, epidural ropivacaine consumption, and additional analgesic
      requirements during the first 48 hours postoperatively. Results: Forty-seven
      patients completed the study, 23 in the preemptive group and 24 in the control
      group, respectively. The revised Face, Legs, Activity, Cry, and Consolability
      pain scores were significantly lower in the preemptive group only at 30 minutes
      after postanesthesia care unit arrival and 6 hours after surgery (median
      difference -1.0, 95% CI -2.0 to -1.0, P=0.001 and median difference -2.0, 95% CI 
      3.0 to -1.0, P=0.005, respectively). However, they were not significantly
      different between the groups at 12, 24, and 48 hours postoperatively. Epidural
      ropivacaine consumption and additional analgesic requirements throughout 48 hours
      postoperatively were not significantly different between the groups. Conclusion:
      Intraoperative epidural infusion of ropivacaine did not demonstrate preemptive
      analgesic efficacy within 48 hours postoperatively in children undergoing
      extensive lower limb orthopedic surgery.

PMID- 30288098
TI  - Plasma ropivacaine concentration after TAP block in a patient with cardiac and
      renal failure.
AB  - We report a successful ultrasound-guided transversus abdominis plane (TAP) block
      as an analgesic option for minor abdominal surgery in a 66-year-old patient with
      cardiac, respiratory, and renal dysfunction caused by primary systemic
      amyloidosis. Bilateral TAP blocks with 120 mg (1.8 mg/kg) of ropivacaine provided
      sufficient intra- and postoperative analgesia for insertion of a continuous
      ambulatory peritoneal dialysis catheter. However, the plasma concentration of
      ropivacaine reached a maximum of 2.5 ug/mL at 15 minutes after the TAP block, a
      concentration that was potentially neurotoxic. Although apparent signs of local
      anesthetic systemic toxicity (LAST) such as convulsion or changes in an
      electrocardiogram were not observed, the patient became drowsy after the TAP
      block, which might be one of the mild symptoms of LAST. A TAP block by itself can
      thus be an anesthetic option for patients undergoing minor abdominal surgery.
      However, cardiac and renal dysfunction might influence the pharmacokinetics of a
      local anesthetic used, and attention should be paid to the possibility of LAST
      even with a low dose of a local anesthetic for patients with cardiac and renal
      failure.

PMID- 30288097
TI  - Exercise as a tool for hypertension and resistant hypertension management:
      current insights.
AB  - Although there has been an observed progress in the treatment of hypertension,
      its prevalence remains elevated and constitutes a leading cause of cardiovascular
      disease development. Resistant hypertension is a challenge for clinicians, as the
      available treatment options have reduced success. Physical activity and exercise
      training play an important role in the management of blood pressure. The
      importance of physical activity and exercise training as part of a comprehensive
      lifestyle intervention is acknowledged by several professional organizations in
      their recommendations/guidelines for the management of arterial hypertension.
      Aerobic exercise, dynamic resistance exercise, and concurrent training - the
      combination of dynamic resistance and aerobic exercise training in the same
      exercise session or on separate days - has been demonstrated to reduce blood
      pressure and help in the management of hypertension. The present review draws
      attention to the importance of exercise training in the management of blood
      pressure in both hypertension and resistant hypertension individuals.

PMID- 30288099
TI  - Impact of CT slice thickness on volume and dose evaluation during thoracic cancer
      radiotherapy.
AB  - Introduction: Accurate delineation of targets and organs at risk (OAR) is
      required to ensure treatment efficacy and minimize risk of normal tissue toxicity
      with radiotherapy. Therefore, we evaluated the impacts of computed tomography
      (CT) slice thickness and reconstruction methods on the volume and dose
      evaluations of targets and OAR. Patients and methods: Eleven CT datasets from
      patients with thoracic cancer were included. 3D images with a slice thickness of
      2 mm (2-CT) were created automatically. Images of other slice thickness (4-CT, 6
      CT, 8-CT, 10-CT) were reconstructed manually by the selected 2D images using two
      methods; internal tumor information and external CT Reference markers. Structures
      and plans on 2-CT images, as a reference data, were copied to the reconstructed
      images. Results: The maximum error of volume was 84.6% for the smallest target in
      10-CT, and the maximum error (>=20 cm3) was 10.1%, 14.8% for the two
      reconstruction methods, internal tumor information and external CT Reference,
      respectively. Changes in conformity index for a target of <20 cm3 were 5.4% and
      17.5% in 8-CT. Changes on V30 and V40 of the heart were considerable. In the
      internal tumor information method, volumes of hearts decreased by 3.2% in 6-CT,
      while V30 and V40 increased by 18.4% and 46.6%. Conclusion: The image
      reconstruction method by internal tumor information was less affected by slice
      thickness than the image reconstruction method by external CT Reference markers.
      This study suggested that before positioning scanning, the largest section
      through the target should be determined and the optimal slice thickness should be
      estimated.

PMID- 30288100
TI  - Decreased expression of TRIM21 indicates unfavorable outcome and promotes cell
      growth in breast cancer.
AB  - Background: Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin
      ligase, has been implicated in autoimmune diseases. Dysregulation of TRIM21
      contributes to the progression of human malignancies, but its role and clinical
      significance in breast cancer remain unclear. Methods: The expression of TRIM21
      was examined by quantitative real-time PCR, Western blot, and
      immunohistochemistry. The role of TRIM21 in the progression of breast cancer was
      determined using in vitro and in vivo models. The upstream regulation of TRIM21
      was investigated by luciferase reporter assay. Results: Here, we showed that
      TRIM21 expression in breast cancer tissues was decreased at both the mRNA and
      protein levels in comparison to that in nontumorous tissues. TRIM21 expression
      was closely associated with tumor size, estrogen receptor, human epidermal growth
      factor receptor 2, and clinical stage. Low TRIM21 expression was correlated with
      poor overall and disease-free survival in two independent cohorts containing
      1,219 patients with breast cancer. A multivariate Cox regression model suggested
      TRIM21 as an independent factor for overall survival. In vitro data revealed that
      TRIM21 expression was suppressed by miR-494-3p directly targeting the 3'
      untranslated region of TRIM21. Overexpression of TRIM21 impeded cell
      proliferation and tumor growth in breast cancer, whereas TRIM21 depletion
      enhanced these capacities. Conclusion: Collectively, our findings indicate that
      TRIM21 serves as a potential prognostic biomarker and functions as a tumor
      suppressor in breast cancer.

PMID- 30288101
TI  - Low expression of VSIG4 is associated with poor prognosis in hepatocellular
      carcinoma patients with hepatitis B infection.
AB  - Background: V-set and immunoglobulin domain containing protein 4 (VSIG4) was
      reported to play an important role in tumorigenesis. However, the expression and
      clinical relevance in hepatocellular carcinoma (HCC) remain unknown. Materials
      and methods: First, the mRNA profiles of HCC were screened from The Cancer Genome
      Atlas (TCGA) and Gene Expression Omnibus databases. VSIG4, a differentially
      expressed gene that has not been reported in HCC, was distinguished. Second, the
      correlation between VSIG4 expression and the prognosis of HCC patients from TCGA
      was analyzed. Third, VSIG4 mRNA level was detected in 36 pairs of HCC tissues and
      4 HCC cell lines by PCR assay. And finally, prognosis analysis was assessed for
      36 HCC patients with different expression levels of VSIG4. Results:
      Bioinformatics analysis showed that VSIG4 expression was downregulated in HCC
      tissues, and the expression level of VSIG4 was negatively correlated with serum
      alpha fetal protein (AFP) level and tumor distant metastasis. Survival analysis
      of all HCC patients in TCGA indicated that the overall survival and disease-free
      survival were not significantly associated with VSIG4 expression. However,
      subgroup analysis showed that in the patients with hepatitis B virus-related HCC,
      both overall survival and disease-free survival were shorter in the low VSIG4
      expression group. Our PCR results further showed that VSIG4 expression was
      significantly decreased in HCC tissues and HCC cell lines, and the disease-free
      survival in hepatitis B virus-related HCC patients with low VSIG4 expression was
      shorter than in those with high VSIG4 expression, which was consistent with the
      bioinformatics analysis results. Conclusion: Our study suggests that VSIG4 is
      downregulated in HCC, and low expression of VSIG4 is associated with poor
      prognosis in hepatitis B virus-related HCC patients.

PMID- 30288102
TI  - A model combining TNM stage and tumor size shows utility in predicting recurrence
      among patients with hepatocellular carcinoma after resection.
AB  - Objective: Hepatocellular carcinoma (HCC) recurrence is a clinical challenge. An
      accurate prediction system for patients with HCC is needed, since the choice of
      HCC treatment strategies is very important. Patients and methods: A total of 804
      patients with HCC who underwent curative resection at Sun Yat-sen University
      Cancer Center were included in this study. Demographics, clinicopathological
      data, and follow-up information were collected. Results: A logistic regression
      analysis was conducted to investigate the relationships between clinical features
      and HCC recurrence. Tumor size (OR=1.454, 95% CI: 1.047-2.020, P=0.026) and TNM
      stage (OR=1.360, 95% CI: 1.021-1.813, P=0.036) were independent predictors of HCC
      recurrence after curative resection. Therefore, the following equation was
      established to predict HCC recurrence: 0.308*TNM+0.374*tumor size-0.639. The
      equation score was 0.53+/-0.23 in patients who experienced HCC recurrence
      compared with 0.47+/-0.24 in other patients. A similar trend was observed in
      patients who survived after the last follow-up, compared with those who did not,
      with scores of 0.37+/-0.26 vs 0.52+/-0.22, respectively (P<0.001). The Kaplan
      Meier analysis showed that patients with HCC with equation values >0.5 had
      significantly worse outcomes than those with equation values <=0.5 (P<0.001) for
      overall survival (OS) and recurrence (P=0.043). Multivariate Cox analyses showed
      that tumor multiplicity (P=0.039), involucrum (P=0.029), vascular invasion
      (P<0.001), and equation value (P<0.001) were independent prognostic variables for
      OS, whereas tumor multiplicity (P=0.01), tumor differentiation (P=0.007),
      vascular invasion (P<0.001), involucrum (P=0.01), and equation value (P<0.001)
      were independent prognostic variables for HCC recurrence. Conclusion: We
      established a novel and effective equation for predicting the probability of
      recurrence and OS after curative resection. Patients with a high recurrence
      score, based on this equation, should undergo additional high-end imaging
      examinations.

PMID- 30288103
TI  - An expression signature model to predict lung adenocarcinoma-specific survival.
AB  - Background: The current TNM staging system plays a central role in lung
      adenocarcinoma (LUAD) prognosis. However, it may not adequately stratify the risk
      of tumor recurrence. With the aid of gene expression profiling, we identified 31
      lncRNAs whose expressions in tumor tissues could be used as a risk indicator for
      the guidance of lung cancer therapy. This exploratory analysis may shed new light
      on identification of potential prognostic factors. Materials and methods: A
      survival prediction scoring model was developed from the data that are publicly
      available in The Cancer Genome Atlas (TCGA) LUAD RNA Sequencing dataset.
      Multivariate Cox regression analysis and Kaplan-Meier analysis were performed on
      a cohort of 254 stage I lung carcinoma patients with survival records. Results:
      Our model indicates that the panels comprising 31 lncRNAs are highly associated
      with overall survival (OS): 18.9% (95% CI: 10.4%-34.5%) and 89.5% (95% CI: 80.7%
      99.2%) for the high- and low-risk group, respectively. The specificity and
      sensitivity of the model are verified, which show that the area under receiver
      operating characteristic curve yields 0.881, meaning our model has good accuracy
      and it is feasible for further applications. Conclusion: The 31-lncRNA model
      might be able to predict OS in patients with LUAD with high accuracy. Its further
      applications in biomolecular experiments using clinical samples with independent
      cohorts of patients are needed to verify the results.

PMID- 30288104
TI  - Stereotactic radiosurgery for vestibular schwannomas.
AB  - Stereotactic radiosurgery (SRS) maintains an important role in managing
      vestibular schwannoma (VS). Long-term clinical data have clearly established the
      safety and efficacy of the procedure for managing Koos low grade to intermediate
      grade VS. Historically, the procedure was developed via a multidisciplinary
      approach that involves physicians (eg, neurosurgeons and radiation oncologists)
      as well as clinical specialists (eg, radiation physicists). In this paper, we
      have reviewed current technical and clinical practices of SRS for VS from a
      procedural specialist's perspective and from a clinician's perspective.

PMID- 30288106
TI  - S100A9 regulates cisplatin chemosensitivity of squamous cervical cancer cells and
      related mechanism.
AB  - Objective: Our previous research has shown that the expression of S100 calcium
      binding protein A9 (S100A9) in tumor cells was associated with neoadjuvant
      chemotherapy sensitivity in cervical squamous cell carcinoma. In the present
      study, we altered the expression of S100A9 through infecting lentivirus,
      investigated its effect on the chemosensitivity to cisplatin of cervical cancer
      cells and then made a primary exploration of the involved mechanism. Materials
      and methods: Lentivirus was employed to upregulate and downregulate S100A9
      expression in SiHa cells. The protein expression level of apoptotic-related
      proteins Bcl-2 and Bax, drug resistance-related proteins multiple drug resistance
      protein 1 (MRP1), P glycoprotein (P-gp), glutathione-S-transferase-pi (GST-pi),
      lung resistance-related protein (LRP), and FOXO1 signaling pathway related
      proteins was detected by Western blot. The CCK-8 assay was used to examine
      chemosensitivity to cisplatin, and the proportion of apoptosis cells was analyzed
      by the flow cytometry. Results: S100A9 overexpression could obviously increase
      the IC50 value of SiHa cells to cisplatin and decrease the apoptosis rate induced
      by cisplatin. Downregulation of S100A9 led to the opposite results. In S100A9
      overexpression SiHa cells, the expression level of Bcl-2, LRP, GST-pi, p-AKT, p
      ERK, p-FOXO1, and Nanog was significantly increased, while FOXO1 expression was
      decreased. The opposite results were observed in S100A9 knockdown SiHa cells.
      Conclusion: Downregulation of S100A9 could significantly increase apoptosis rate,
      resulting in enhancing sensitivity of SiHa cells to cisplatin, which may be
      related to Bcl-2, GST-pi, and LRP protein and by altering the AKT/ERK-FOXO1-Nanog
      signaling pathway.

PMID- 30288107
TI  - The impact of biopsy sampling errors and the quality of surgical margins on local
      recurrence and survival in chondrosarcoma.
AB  - Purpose: To examine the frequency of computed tomography (CT)-guided biopsy
      sampling errors in chondrosarcomas, as well as the impact of these errors and the
      achieved surgical margins on local recurrence-free survival (LRFS) and disease
      specific survival (DSS). Material and methods: A total of 68 consecutive patients
      treated for chondrosarcoma from 2000-2015 were retrospectively reviewed with a
      minimum follow-up duration of 2 years. Results: The primary location was at the
      extremities in 46 patients (67.6%) and at the axial skeleton in 22 patients
      (32.4%). Seven patients underwent planned intralesional curettage. Surgical
      margins were assessed in the remaining 53 patients and included 21 wide (39.6%),
      25 marginal (47.1%), and seven intralesional (13.2%) resections. Biopsy sampling
      errors occurred in ten patients (14.7%). LRFS was 82.2+/-7.8% at 5 years and
      76.9+/-7.8% at 10 years. An intact anatomical barrier was associated with the
      most preferable LRFS of 89+/-10.5% after 10 years. DSS was 79.2+/-8.5% at 5 years
      and 75.5+/-6.4% at 10 years. The metric distance of the surgical margin and the
      presence of a biopsy sampling error did not affect either LRFS or DSS.
      Conclusion: Even though histological grading in chondrosarcoma is difficult,
      sampling errors in preoperative biopsies are relatively rare and do not adversely
      affect outcomes. The presence of an anatomical barrier has a greater impact on
      LRFS than the metric distance of the surgical margins.

PMID- 30288108
TI  - Spotlight on cabozantinib for previously untreated advanced renal cell carcinoma:
      evidence to date.
AB  - Background: In the past few years, new drugs made their appearance in the first
      line setting of treatment for metastatic renal cell carcinoma (mRCC), and
      cabozantinib is one among them. The present systematic review aims to point out
      any evidence published to date about first-line treatment with cabozantinib for
      mRCC patients, describing their outcome in all end points explored by the
      literature. Methods: PRISMA guidelines were followed. A systematic assessment of
      literature and peer- reviewed presentations was performed by searching PubMed and
      major oncology meeting resources, from the database inception until June 25,
      2018. The following keywords were used: "cabozantinib or cabozantinib-s-malate or
      XL184" and "renal cell carcinoma or kidney cancer or clear cell renal carcinoma
      or renal cancer" and "first-line or untreated or treatment-naive or primary
      treatment". All types of original clinical studies were included, evaluating
      either cabozantinib monotherapy or any systemic drug combination containing
      cabozantinib for previously untreated patients with mRCC. Results: From potential
      75 titles and abstracts, seven publications were selected. One was the main
      report of a randomized clinical trial (the CABOSUN study); four papers reported
      updated results, secondary or subgroup analyses from the same study population;
      and further two reports consisted of network meta-analyses. From the additional
      search for ongoing clinical trials, six studies currently in progress were
      reported. Conclusion: According to the reported evidence, cabozantinib may be a
      viable first-line option in mRCC patients with intermediate or poor risk
      according to International Metastatic Renal Cell Carcinoma Database Consortium
      model. It offers an undoubtful advantage in terms of progression-free survival,
      despite quite high rates of G3-4 toxicity, modest objective response rate, and no
      survival advantage. Nevertheless, given the availability of an immunotherapy
      combination that significantly improved overall survival for the same population
      in a Phase III trial and the indisputable efficacy of cabozantinib as second-line
      treatment, this drug may be devoted as a rescue option in patients progressive to
      primary therapy.

PMID- 30288105
TI  - Emerging clinical significance of claudin-7 in colorectal cancer: a review.
AB  - Tight junctions (TJs) play an important role in maintaining cell polarity and
      regulating cell permeability. In recent years, many studies have shown that TJ
      proteins, especially claudin-7, are closely related to inflammation and the
      development of various malignant tumors. Claudin-7 plays a significant role in
      maintaining the physiological functions and pathological conditions of the TJ
      barrier. The dysregulation of claudin-7 plays a tumor suppressor role or
      conversely has carcinogenic effects in different target tissues or cells, but the
      exact underlying mechanism is still unclear. In this review, we will summarize
      the expression pattern of claudin-7 in tumors, focusing on the expression and
      regulation of claudin-7 in colorectal cancer and discussing the correlation
      between claudin-7 and invasion, metastasis and epithelial-mesenchymal transition
      (EMT) in colorectal cancer. The construction of Cldn7-/- mice and conventional
      claudin-7 knockout mouse models has helped determine the mechanisms by which
      claudin-7 promotes tumorigenesis. Elucidation of the expression and subcellular
      localization of claudin-7 under pathological conditions will help develop claudin
      7 as a useful biomarker for detecting and diagnosing cancer, and thus may help
      combat the occurrence, development, and invasion of cancers.

PMID- 30288110
TI  - Ethylacetate extract from Tetrastigma hemsleyanum inhibits proliferation and
      induces apoptosis in HepG2 and SMMC-7721 cells.
AB  - Purpose: This study aimed to investigate the effect of ethylacetate extract from
      Tetrastigma hemsleyanum (EET) on the proliferation and apoptosis of HepG2 and
      SMMC-7721 cells and determine the underlying mechanisms. Materials and methods:
      HepG2 and SMMC-7721 cells were cultured in vitro until the exponential growth
      phase and then treated with different concentrations of EET for 24 h. We
      performed a colony forming assay to determine colony forming ability, CCK8 assay
      to detect cell proliferation, Annexin V-FITC/PI double staining to analyze cell
      apoptosis, and Western blot to measure the protein expression of Caspase-3, Bcl
      2, and Bax. Results: EET significantly inhibited the proliferation of HepG2 and
      SMMC-7721 cells in a concentration- and time-dependent manner (P<0.05). After
      treatment with 0, 50, 100, 150, 200, and 250 MUg/mL EET for 24 h, HepG2 the
      proliferation rates were 100.00%+/-0.00%, 90.33%+/-1.76%, 67.67%+/-0.88%,
      47.33%+/-0.88%, 37.00%+/-0.00%, and 30.33%+/-0.67%, respectively, and 100.00%+/
      0.00%, 18.25%+/-1.05%, 19.99%+/-0.59%, 23.42%+/-0.46%, 29.70%+/-0.79%, and
      29.8%+/-0.41% for SMMC-7721 cells, respectively. After treatment with 0, 50, 100,
      150, 200, and 250 MUg/mL EET for 24 h, the apoptotic rates were 11.08%+/-0.72%,
      27.44%+/-0.51%, 32.92%+/-0.41%, 26.20%+/-0.47%, 22.92%+/-0.24%, and 55.60%+/
      0.08%, for HepG2 cells, respectively, and 59.18%+/-0.17%, 41.24%+/-2.05%,
      52.54%+/-0.39%, 50.54%+/-1.08%, and 57.44%+/-1.93% for SMMC-7721 cells,
      respectively. Compared with the treatment groups, the control group showed a
      significantly lower apoptotic rate (47.91%+/-1.09%, P<0.05). EET at the different
      concentrations downregulated the protein expression of Caspase-3 in HepG2 cells
      and upregulated it in SMMC-7721 cells; it also downregulated the protein
      expression of Bcl-2 in HepG2 and SMMC-7721 cells and upregulated the protein
      expression of Bax in HepG2 and SMMC-7721 cells. Conclusion: These findings
      suggest that EET exerts antiproliferative and proapoptotic effects against HepG2
      and SMMC-7721 cells mediated by downregulation or upregulation of Caspase-3
      expression. Our study may help to develop EET for the pharmacological treatment
      of hepatoblastoma or hepatocellular carcinoma.

PMID- 30288109
TI  - Secondhand smoking increases bladder cancer risk in nonsmoking population: a meta
      analysis.
AB  - Background: Tobacco smoking has been widely acknowledged to be the most important
      risk factor for bladder cancer. However, whether secondhand smoking (SHS)
      increases the risk of bladder cancer still remains uncertain. We conducted a meta
      analysis about the risk of bladder cancer and lifetime SHS and childhood SHS.
      Materials and methods: We searched PubMed, EMBASE, Web of Science, and Chinese
      National Knowledge Infrastructure (CNKI) up to March 12, 2018, and checked
      references of the retrieved articles and relevant reviews to include 14 studies.
      Relative risk (RR) and 95% confidence interval (CI) were used to assess this
      risk. Results: The pooled RR of 14 eligible studies based on the retrieved
      articles and relevant reviews illustrated a significantly increased risk of
      bladder cancer with RR 1.22, 95% CI 1.06-1.4. No heterogeneity or publication
      bias was found. But we need more evidence to prove a more reliable association
      between childhood SHS and bladder cancer. Conclusion: There was a statistically
      significant 22% increased risk of bladder cancer for lifetime SHS exposure in
      nonsmoking patients compared with unexposed nonsmoking population. But the
      association between childhood SHS exposure compared with unexposed nonsmoking
      population was unclear. Further research should be conducted to confirm our
      findings and reveal the potential biological mechanisms.

PMID- 30288111
TI  - Polymorphisms in AURKA and AURKB are associated with the survival of triple
      negative breast cancer patients treated with taxane-based adjuvant chemotherapy.
AB  - Purpose: Triple-negative breast cancer (TNBC) is more than a single disease.
      Identifying biomarkers to further subdivide TNBC patients with distinct outcome
      is of great importance. It has been reported that single-nucleotide polymorphisms
      (SNPs) in Aurora kinase A (AURKA) or Aurora kinase B (AURKB) are associated with
      the risk and survival of several cancers. But till now, there is no research
      about these polymorphisms in TNBC patients. Materials and methods: In this study,
      we investigated the association between polymorphisms in AURKA or AURKB gene and
      prognosis of TNBC patients treated with taxane-based adjuvant chemotherapy. A
      total of 273 TNBC patients were enrolled. Haploview 4.2 software was used to
      identify Tag SNPs. Genotyping was conducted using the MassARRAY MALDI-TOF system.
      Results: We found that AURKA rs6099128 GG genotype carriers had significantly
      worse overall survival (OS) than TT+ TG genotype carriers (P = 0.003, HR =
      12.499, 95% CI = 2.357-66.298). AURKB rs11651993 TT genotype carriers had better
      disease-free survival (DFS) than TC + CC genotype carriers (P = 0.018, HR =
      1.876, 95% CI = 1.116-3.154). AURKB rs2289590 CC genotype carriers had worse DFS
      than CA + AA genotype carriers (P = 0.021, HR = 0.536, 95% CI = 0.315-0.912).
      After subgroup analysis, rs11651993 TC + CC genotype predicted worse DFS in
      subgroups of age <= 50, post-menopausal, grade unknown (UK), tumor size >2 cm,
      and lymph node negative. Rs2289590 CA + AA genotype could predict favorable DFS
      in pre-menopausal, grade 3 and lymph node-positive patients. Conclusion: We first
      demonstrated that polymorphisms in AURKA or AURKB gene might predict the OS or
      DFS of TNBC patients treated with taxane-based adjuvant chemotherapy.

PMID- 30288112
TI  - Efficacy and safety of de-escalation bone- modifying agents for cancer patients
      with bone metastases: a systematic review and meta-analysis.
AB  - Background: Compared with application of bone-modifying agents (BMAs) every 4
      weeks, it is unclear whether 12-weekly de-escalated therapy can be used as a
      substitute strategy. Methods: A systematic search of PubMed, EMBASE, and the
      Cochrane Register of Controlled Trials until November 22, 2017, was performed.
      Randomized controlled trials (RCTs) were included to assess skeletal-related
      event (SRE) rates, adverse events, and bone turnover biomarkers, comparing 12
      weekly de-escalated treatments with standard 4-weekly dosage regimens. Risk
      ratios (RRs) with 95% CIs were pooled in fixed-effect meta-analyses. Results: A
      total of eight citations were eligible comprising 2,878 patients: zoledronate
      (three studies, 2,650 patients), pamidronate (two studies, 68 patients), and
      denosumab (three studies, 160 patients). Summary RR (0.98; 95% CI 0.87-1.12;
      P=0.82) for SRE rates between de-escalated and standard arms was produced when
      seven low risk of bias trials (695 patients) were pooled, and results without
      statistical significance also appeared in the analysis of adverse events and bone
      turnover biomarkers. Due to the limited sample size and methodological
      differences, the data for skeletal morbidity rates (SMRs), time to first SRE,
      serum C-telopeptide (sCTx) levels, and hypocalcemia were not combined, but
      systematic review still obtained similar indistinguishableness. Conclusion: In
      this meta-analysis of randomized clinical trials, the results "appeared" to show
      non-inferiority of the 12-weekly treatment. Due to the difference in available
      data, the results for bisphosphonates are more solid than for the receptor
      activator of nuclear factor-kappaB ligand (RANKL) antibodies.

PMID- 30288113
TI  - Computed tomography scan efficacy in staging gastric linitis plastica lesion: a
      retrospective multicentric French study.
AB  - Background: Computed tomography (CT) scan is a key imaging technique in the
      staging of gastric adenocarcinoma and therapeutic management of patients. The aim
      of this study was to evaluate the performance of CT scan in the staging of
      parietal and metastatic invasion in gastric linitis plastica group. Methods: A
      retrospective multicentric French study was conducted from January 2006 to
      December 2015 on patients with no metastatic gastric linitis plastica and
      operated by gastrec-tomy. A 2/1 matching based on pTNM stage and center was
      performed. Results: Fifty patients were included in the linitis plastica group
      and 100 in the control group. Patients from the linitis group were significantly
      different from those from the control group with a lower age at diagnosis, a more
      advanced histological lesion, a more frequent undiagnosed peritoneal
      carcinomatosis, and a higher risk of R1 resection. Sensitivity and specificity of
      CT scan for the diagnosis of lymph node involvement were 44% and 75%,
      respectively, in the linitis plastica group and 55% and 60%, respectively, in the
      control group. The sensitivity and specificity of CT scan for the T3-T4 parietal
      invasion were 26% and 100%, respectively, in the linitis group and 40% and 72%,
      respectively, in the control group. Conclusion: CT scan has an equal sensitivity
      and specificity for the evaluation of lymph node and parietal involvement in
      gastric adenocarcinoma, including linitis plastica. CT scan remains the
      cornerstone of preoperative evaluation in gastric adenocarcinoma, including
      linitis plastica. However, CT presents a lack of sensitivity to diagnose low
      volume peritoneal carcinomatosis.

PMID- 30288114
TI  - Multidisciplinary therapy for scirrhous gastric cancer: a retrospective analysis
      and proposal of new treatment strategy.
AB  - Background: Scirrhous gastric cancer (SGC) is highly invasive and metastatic
      because of its interactions with stromal cells, such as fibroblasts and
      macrophages, and extracellular matrix, leading to a higher incidence of
      peritoneal metastasis (PM) than other gastric cancers (GCs). Taxane-based
      intraperitoneal chemotherapy (IPC) is a promising therapy for PM. We
      retrospectively analyzed outcomes of multidisciplinary therapies that included
      IPC for SGC. Patients and therapy: Of 1,679 GC patients treated between 1990 and
      2012, we analyzed 119 patients who underwent multidisciplinary therapy for SGC.
      Patients without PM received gastrectomy with lymphadenectomy and resection of
      involved adjacent organs followed by intraoperative IPC using cisplatin. Patients
      with PM received chemotherapy using fluorouracil, with or without methotrexate
      plus IPC using cisplatin before 2000, and S-1 plus IPC using paclitaxel or
      docetaxel since 2000. Results: Of the 119 patients, 73 (61%) had PM and 63 (53%)
      had positive peritoneal lavage cytology. Of the 89 gastrectomy patients, 30 (34%)
      had macroscopic residual tumors (R2). Of the patients treated since 2000, 66
      (100%) received S-1 plus taxanes and 44 patients (67%) received taxane-based IPC.
      Median survival time was significantly longer in the post-2000 group (22.8
      months) than in the pre-2000 group (9.5 months). In univariate analysis, lavage
      cytology, PM, taxane-based IPC, gastrectomy, and R2 resection were significant
      prognostic factors. However, only R2 resection was an independent prognostic
      factor in multivariate analysis (hazard ratio: 5.53, 95% CI: 2.05-14.93).
      Conclusion: As use of taxane-based IPC is not an independent prognostic factor,
      new multidisciplinary therapies are necessary to avoid R2 resections.

PMID- 30288115
TI  - Increased derived neutrophil-to-lymphocyte ratio and Breast Imaging-Reporting and
      Data System classification predict poor survival in patients with non-distant
      metastatic HER2+ breast cancer treated with neoadjuvant chemotherapy.
AB  - Introduction: The prognostic role of the derived neutrophil-to-lymphocyte ratio
      (dNLR) in human patients with HER2+ breast cancer is not well understood. Here,
      we aimed to investigate the prognostic significance of dNLR in patients with
      HER2+ breast cancer undergoing neoadjuvant chemotherapy. Methods: A total of 310
      patients with non-distant metastatic HER2+ breast cancer who had received
      neoadjuvant chemotherapy in our hospital from May 2006 to November 2013 were
      retrospectively included in this study. Kaplan-Meier curves were used to assess
      overall survival (OS) and disease-free survival (DFS). The Cox regression model
      was used to evaluate the prognostic value of dNLR and Breast Imaging-Reporting
      and Data System (BI-RADS) classification, as well as other clinicopathological
      parameters in patients with HER2+ breast cancer treated with neoadjuvant
      chemotherapy. Results: We found that dNLR prior to treatment was positively
      correlated with tumor size, tumor stage, lymphovascular invasion, and
      histological grade (P<0.05). The median OS of patients with high dNLR and low
      dNLR were 44.2 and 69.9, respectively (P<0.001), and the median DFS of patients
      with high dNLR and low dNLR were 15.3 and 22.1 months, respectively (P<0.001).
      Multivariate analysis showed that dNLR was an independent risk factor for OS (HR
      =1.726; 95% CI: 1.072-2.662; P=0.009) and DFS (HR =1.658; 95% CI: 1.125-2.426;
      P=0.026). Moreover, increased BI-RADS classification independently predicted
      short OS (HR =1.609; 95% CI: 1.216-2.351; P=0.015) and DFS (HR =1.925; 95% CI:
      1.526-2.635; P=0.021). Conclusion: dNLR prior to treatment and BI-RADS
      classification are independent prognostic factors in patients with HER2+ breast
      cancer receiving neoadjuvant chemotherapy.

PMID- 30288116
TI  - Metabolic syndrome and the risk of cholangiocarcinoma: a hospital-based case
      control study in China.
AB  - Background: Metabolic syndrome is regarded as a risk factor for hepatocellular
      carcinoma. However, no research has been conducted to investigate the association
      between metabolic syndrome and cholangiocarcinoma (CCA), especially in the
      Chinese population. Herein, a hospital-based case-control study was carried out
      in China to explore the association between metabolic syndrome and CCA risk.
      Patients and methods: In this study, 303 CCA patients (136 intrahepatic
      cholangiocarcinoma [ICC] and 167 extrahepatic cholangiocarcinoma [ECC]) were
      included, who were observed at Peking Union Medical College Hospital (PUMCH),
      from 2002 to 2014. Healthy controls were randomly selected from the database of
      PUMPH Health Screening Center. We retrospectively extracted metabolic syndrome
      and other possible risk factors from clinical records, followed by investigation
      of the relationship with CCA via calculation of ORs and 95% CIs using logistic
      regression analysis. Results: Metabolic syndrome was significantly and positively
      correlated with all CCA subtypes, with adjusted ORs (AORs) of 0.35 (95% CI =0.29
      0.42) and 0.29 (95% CI =0.19-0.44) for ICC and ECC, respectively (both P<0.001).
      Dyslipoproteinemia harbored a stronger relationship with ICC (OR =3.16; 95% CI
      =2.12-4.71) than ECC (OR =1.87; 95% CI =1.27-2.77), whereas hypertension harbored
      a stronger association with ECC (OR =3.09; 95% CI =2.09-4.58) than ICC (OR =2.06;
      95% CI =1.32-3.21). Obesity was related to both ICC and ECC, with similar ORs,
      while diabetes was only related to ICC (OR =4.59; 95% CI =2.78-7.58), but not ECC
      (OR =0.97; 95% CI =0.49-1.94). Conclusion: Metabolic syndrome was significantly
      related to a 1.86-fold elevated CCA risk.

PMID- 30288117
TI  - CD44 is overexpressed and correlated with tumor progression in gallbladder
      cancer.
AB  - Background: Gallbladder cancer (GBC) is a highly lethal disease and the most
      common biliary tract malignant tumor with poor prognosis. Accumulating evidence
      indicates that cluster of differentiation 44 (CD44) is overexpressed in several
      malignancies and has a crucial role in the development of cancer. However, its
      expression and function in GBC are unclear. The aim of this study was to explore
      CD44 expression and its role in GBC. Materials and methods: The expression of
      CD44 was measured by immunohistochemistry. Tissue microarray analysis was used to
      confirm the relationship between CD44 expression and clinical outcomes of GBC
      patients. EDU assay, colony formation assay, cell migration and invasion assay
      were performed to detect the functions of CD44 in GBC-SD and NOZ transfected with
      si-RNA. Results: CD44 was overexpressed and associated with poor outcomes in GBC
      patients. The univariate and multivariate analyses confirmed that elevated CD44
      was an independent prognostic factor for the OS of GBC patients. Silencing CD44
      could suppress the GBC cell proliferation, migration and invasion in vitro, as
      well as attenuated cancer stem cell functions. Conclusion: CD44 markedly
      correlated with aggressive tumor behaviors and contributed to the progression of
      GBC, which could represent a novel prognostic marker and potential therapeutic
      target for GBC patients.

PMID- 30288118
TI  - Young age increases the risk of lymph node positivity in papillary thyroid cancer
      patients: a SEER data-based study.
AB  - Introduction: Currently in papillary thyroid cancer (PTC), the correlation
      between lymph node positivity (LN+) and patient's age at diagnosis is still
      inconclusive. The aim of this study was to investigate whether younger PTC
      patients had higher LN+ rates. Patients and methods: From the 1998-2013
      Surveillance, Epidemiology, and End Results database, we analyzed PTC patients
      with at least 1 LN examined. The patients were divided into 5 groups by age
      separately for each T stage: <=30; 31-40; 41-50; 51-60; >60 years. Results: A
      total of 46,077 PTC patients were identified, including 8,386 (18.2%) patients
      aged <=30 years, 10,971 (23.8%) patients aged 31-40 years, 11,646 (25.3%)
      patients aged 41-50 years, 8,596 (18.7%) patients aged 51-60 years, and 6,478
      (14.1%) patients aged >60 years. In each T stage, LN+ rates were inversely
      associated with age at diagnosis, which was validated by multivariate logistic
      regression analysis (p<0.001). In addition, the subset of patients 30 or younger
      had the highest lymph node ratio compared with other subsets (p<0.001).
      Conclusion: We identified that younger PTC patients have an increased
      predisposition for LN+ regardless of T stage. This finding could help surgeons to
      select the optimal treatment for younger PTC patients.

PMID- 30288119
TI  - Incidence and distribution of advanced colorectal adenomas in patients undergoing
      colonoscopy for screening, surveillance, and symptoms.
AB  - Purpose: The aim of the study was to determine the frequency and distribution of
      advanced colorectal adenomas (ACAs) in Chinese population. Methods: The patients
      who were referred to receive a colonoscopy were divided into three subgroups of
      screening, surveillance, and symptomatic, and then they were selected based on
      their indications. The symptomatic subgroup was further broken down into the
      alarm and non-alarm categories. The location and morphology of all colorectal
      lesions were both investigated and recorded. Results: There were significantly
      more patients with ACAs in the symptomatic subgroup compared to the screening or
      surveillance subgroup (11.0% vs 4.1%, P<0.001; 11.0% vs 4.6%, P=0.006). No
      differences were found in the ACA frequency between the alarm and non-alarm
      categories (11.7% vs 9.7%, P=0.056). One observation was that in the symptomatic
      subgroup, distal lesions were more likely to contain ACAs than proximal ones (OR
      1.50, 95% CI 1.05-2.15, P=0.024). It was also noted that nonpolypoid lesions had
      significantly higher amounts of ACAs in the symptomatic subgroup (OR 2.09, 95% CI
      1.48-2.94, P<0.001) than the other groups. Conclusion: The incidence of ACAs was
      higher in patients undergoing a colonoscopy due to their symptoms, compared to
      the incidence in those who underwent the procedure for screening or surveillance
      purposes. Additionally, more attention should be focused on distal and
      nonpolypoid lesions to improve the detection rate of ACAs.

PMID- 30288120
TI  - CircZNF609 promotes breast cancer cell growth, migration, and invasion by
      elevating p70S6K1 via sponging miR-145-5p.
AB  - Background: Accumulating evidence suggests that circular RNAs (circRNAs) play
      critical roles in carcinomas. However, the contributions of circRNAs to breast
      cancer remain unclear. Herein, we determined the role of circZNF609 in breast
      cancer. Methods: A total of 143 breast cancer and 38 normal tissues were
      collected to assess the expression of circZNF609 and its relationship with breast
      cancer prognosis. A series of in vitro and in vivo functional experiments were
      carried out to elucidate the role of circZNF609 in breast cancer progression and
      its underlying molecular mechanisms. Results: CircZNF609 was markedly over
      expressed in breast cancer tissues and cell lines, and high circZNF609 expression
      was closely associated with poor outcome. Silencing of circZNF609 inhibited the
      malignant phenotype of breast cancer in vitro and in vivo. Mechanistically, circ
      ZNF609 served as a sponge of miR-145-5p to elevate p70S6K1 expression. Moreover,
      miR-145-5p overexpression or p70S6K1 knockdown abrogated the oncogenic effects of
      circZNF609 in breast cancer. In addition, clinically, a strong negative
      correlation was observed between the expression of circZNF609 and miR-145-5p in
      breast cancer tissues (r=-0.597, P<0.001), whereas a positive correlation between
      circZNF609 and p70S6K1 expression (r=0.319, P<0.001). Conclusion: These data
      suggest that circZNF609 contributes to breast cancer progression, at least
      partly, by modulating the miR-145-5p/p70S6K1 axis, and it may be a potential
      therapeutic target for breast cancer.

PMID- 30288121
TI  - First-line treatment strategies for newly diagnosed chronic myeloid leukemia: a
      network meta-analysis.
AB  - Objectives: With bosutinib proven to be available for frontline treatment, there
      are currently four frontline treatments as well as an additional strategy with
      high-dose imatinib for newly diagnosed chronic myeloid leukemia (CML). Due to the
      lack of direct comparison of high-dose imatinib, dasatinib, nilotinib, and
      bosutinib, we summarized the evidence to indirectly compare the efficacy among
      these treatment options. Methods: In total, 14 randomized clinical trials
      including 5,630 patients were analyzed by direct and mixed-treatment comparisons.
      Outcomes assessed were the following: complete cytogenetic response at 12 months;
      major molecular response at 12, 24, and 36 months; deep molecular response at 12,
      24, 36, and 60 months; early molecular response at 3 months; progression-free
      survival (PFS); overall survival (OS); and Grade 3 or 4 adverse events (AEs).
      Results: The Bayesian network meta-analysis demonstrated that high-dose imatinib
      was less effective than all new-generation tyrosine kinase inhibitors and had a
      higher probability of Grade 3 or 4 AEs. For molecular response, 300 mg of
      nilotinib was likely to be the preferred frontline treatment, as demonstrated by
      higher response rates and faster, deeper, and longer molecular response. For PFS
      and OS, there were high likelihoods (79% and 74%, respectively) that 400 mg of
      nilotinib was the preferred option. For AEs, standard-dose imatinib has the
      highest probability (65%) of being the most favorable toxicity profile.
      Conclusion: Considering the efficacy and toxicity profile, it is not recommended
      to use high-dose imatinib for treatment. This analysis also showed that nilotinib
      has the highest probability to become the preferred frontline agents for treating
      CML.

PMID- 30288122
TI  - Number of radiotherapy treatment machines in the population and cancer mortality:
      an ecological study.
AB  - Objectives: The aim of this study was to assess the association between the
      number of radiotherapy treatment machines (RTMs) in the population and incidence
      adjusted cancer mortality. Methods: Data on cancer incidence and mortality were
      obtained from the GLOBOCAN project (only high-quality data, C3, or higher
      according to GLOBOCAN quality label), information on the number of RTMs from the
      Directory of Radiotherapy Centers database, and remaining data from the World
      Bank and World Health Organization database. We used linear regression models to
      assess the associations between RTM per 10,000,000 inhabitants (logarithmized)
      and the log-transformed mortality/incidence ratio. Models were adjusted for
      public health variables. To assess the bias due to unobserved confounders,
      mortality from leukemia was considered as a negative control. Here radiotherapy
      treatment is less frequently applied, but a common set of confounders is shared
      with cancer types where radiotherapy plays a stronger role, enabling us to
      estimate the bias due to confounding of unmeasured parameters. To assess an
      exposure-effect size relationship, estimated cancer type-specific estimates were
      related to the proportion of subjects receiving radiotherapy. Results: We found
      an inverse linear relationship between RTM in the population and the cancer
      mortality to incidence ratio for prostate cancer (14.1% per doubling of RTM; 95%
      CI: 0.1%-26.1%), female breast cancer (12.3%; 95% CI: 2.7%-20.9%), and lung
      cancer in women (11.2%; 95% CI: 4.3%-17.6%). There was no evidence for bias due
      to unobserved confounders after covariate adjustment. For women, an exposure
      effect size relationship was found (P=0.02). Conclusion: In this ecological
      study, we found evidence that the population density of RTM is related to cancer
      mortality independently of other public health parameters.

PMID- 30288123
TI  - Determinants of incident asthma-COPD overlap: a prospective study of 55,110
      middle-aged adults.
AB  - Background and aim: Knowledge of the impact of social determinants driving asthma
      chronic obstructive pulmonary disease overlap (ACO) is lacking. Our objective
      was to identify determinants of incident ACO. Methods: A total of 55,053 adults
      (50-64 years) enrolled in the Danish Diet, Cancer, and Health cohort (1993-97)
      was followed in the National Patient Registry for admissions for asthma (DJ45-46)
      and chronic obstructive pulmonary disease (COPD; DJ40-44) and vital status.
      Incident ACO was defined as at least one hospital admission for both asthma and
      COPD (different time points, one after baseline). Detailed case history was
      obtained at baseline. Cox proportional hazards model was used to examine
      associations between possible determinants and incident ACO, in terms of hazard
      ratio (HR) and 95% confidence interval (CI). Results: During follow-up, 561
      incident cases of ACO were identified. Age (HR 4.4, 95% CI 3.3-5.9, age group 60
      65 years), current smoking (HR 3.6, 95% CI 2.8-4.6), unemployment (HR 1.5, 95% CI
      1.2-1.8), and being divorced (HR 1.5, 95% CI 1.2-1.9) determined a higher risk of
      incident ACO, whereas the opposite was found for leisure-time physical activity
      (HR 0.7, 95% CI 0.6-0.8) and high educational level (HR 0.7, 95% CI 0.5-0.9). In
      contrast to ACO, preexisting myocardial infarction (MI; HR 1.5, 95% CI 1.2-1.8)
      and stroke (HR 1.5, 95% CI 1.2-1.9) were associated with a higher risk of COPD.
      Conclusion: Incident ACO is to a large extent determined by factors related to
      lifestyle and socioeconomic status.

PMID- 30288124
TI  - Use of bone-modifying agents among breast cancer patients with bone metastasis:
      evidence from oncology practices in the US.
AB  - Purpose: Bone-modifying agents (BMAs) are recommended for women with bone
      metastasis from breast cancer to prevent skeletal-related events. We examined the
      usage patterns and identified the factors associated with the use of BMAs
      (denosumab and intravenous bisphosphonates) among women in the US. Patients and
      methods: Electronic health records from oncology clinics were used to identify
      women diagnosed with bone metastasis from breast cancer between 2013 and 2014.
      Patients were excluded if they had recently used a BMA or had concurrent cancer
      at an additional primary site. The incidence of BMA initiation, interruption, and
      reinitiation were estimated using competing risk regression models. A generalized
      linear model was used to estimate risk factors for treatment initiation and
      interruption. Results: There were 589 women diagnosed with bone metastasis from
      breast cancer. By 1 year, 68% of these patients (95% CI: 64%, 71%) had initiated
      treatment with a BMA. Denosumab and zoledronic acid were the most commonly used
      agents, whereas pamidronate was used infrequently. Young women were more likely
      to initiate a BMA than older women (adjusted risk difference: 6.4 [95% CI: 1.5,
      10.9]). Of the 412 patients who initiated a BMA, 46% (95% CI: 41%, 51%)
      experienced an interruption within 1 year. Seventy-four percent (95% CI: 68%,
      79%) of patients who interrupted their treatment had reinitiated therapy within 1
      year of interruption. Conclusion: The majority of women diagnosed with bone
      metastasis from breast cancer initiate a BMA within 1 year of diagnosis, but a
      large proportion, particularly among the elderly, do not use these therapies.

PMID- 30288125
TI  - Locating the second mesiobuccal canal in maxillary molars: challenges and
      solutions.
AB  - The second mesiobuccal canal in mesiobuccal roots in maxillary molars is a common
      finding in root canal treatments. Failure on the location of these canals is
      associated with a high rate of unsuccessful treatments of maxillary molars. Its
      prevalence has been assessed in several in vitro and in vivo studies, presenting
      variations according to the methodology applied, along with the population of
      interest. While the anatomy of these teeth is well defined in micro-computed
      tomography studies, the clinical management is a great challenge for the
      practitioner. The use of a dental operating microscope has rendered a better
      clinical outcome when considering the location and treatment of this canal. On
      the other hand, cone-beam computed tomography use is still controversial in the
      efficacy of MB2 canal location. The association of a dental operating microscope
      with troughing performed with ultrasonic tips is an essential step in this
      location. Moreover, sodium fluorescein might be applied for root canal location.
      Due to the high rate of unsuccessful cases when the MB2 canal is not initially
      found, several cases are performed aiming to address the cases of missed MB2
      canals. Therefore, the clinician should discuss the best possible approach,
      whether surgical or clinical. This article presents an overview of the importance
      of the MB2 canal on the outcomes of root canal treatments of maxillary molars.
      Solutions based in current literature will be presented accordingly.

PMID- 30288126
TI  - Seroprevalence of Toxoplasma gondii and its associated risk factors among women
      of reproductive age in Saudi Arabia: a systematic review and meta-analysis.
AB  - Toxoplasma gondii (T. gondii), which infects many warm-blooded animals including
      humans, causes toxoplasmosis, a globally widespread condition. To date, no
      research has explored the overall T. gondii infection seroprevalence among women
      in Saudi Arabia, nor have the risk factors associated with the infection been
      examined in the Saudi Arabian context. The present systematic review and meta
      analysis therefore aimed to investigate toxoplasmosis seroprevalence based on
      previous study samples of Saudi women of reproductive age, and to establish the
      potentially risk factors in this national context. PubMed, Science Direct, and
      Scopus were searched for studies on T. gondii seroprevalence among women in
      mainland Saudi Arabia published between January 2000 and December 2017.
      Seroprevalence with 95% CI was presented for each study, and point estimates and
      their 95% CIs of pooled seroprevalence were then calculated. Twenty papers were
      eligible for inclusion, with samples totaling 13,597 females of childbearing age
      (ie, between 15 and 49 years) covering various regions of Saudi Arabia. The
      pooled estimation for T. gondii prevalence using a random-effect model was
      calculated as 27.8% (95% CI =20.6%-36.3%). A significant association was observed
      between age and T. gondii seroprevalence. This review represents the first
      comprehensive and systematic evaluation of T. gondii infection seroprevalence
      among Saudi Arabian women, and reports a high prevalence of Toxoplasma infection.
      Further research is required to support the development of more cost-effective
      preventive strategies.

PMID- 30288128
TI  - Gradual spontaneous resolution of corneal bloodstaining after anterior chamber
      irrigation for rebleeding secondary to traumatic hyphema.
AB  - Corneal bloodstaining, which is brown or dark yellow in color, is induced by
      hemoglobin deposition, and its breakdown products extend into the corneal stroma.
      In this article, we report a rare case of corneal bloodstaining induced by total
      hyphema after rebleeding for traumatic hyphema. The patient underwent irrigation
      of the anterior chamber (AC) and cataract surgery of the right eye after trauma.
      After oral and topical treatment the imprint of corneal bloodstaining faded, and
      it nearly disappeared after the procedures. Corneal bloodstaining is undoubtedly
      a vision-threatening complication of total hyphema after ocular trauma, surgical
      intervention, and even rebleeding. Removal of the total hyphema as soon as
      possible decreases the severity of corneal bloodstaining, shortens the course of
      spontaneous healing, and thus improves vision.

PMID- 30288127
TI  - A randomized controlled pilot trial of a smoking cessation intervention for US
      women living with HIV: telephone-based video call vs voice call.
AB  - Background: People living with HIV smoke at a rate three times that of the
      general population. This randomized controlled pilot trial tested the feasibility
      and acceptability of a video-call smoking cessation intervention in women living
      with HIV and its preliminary efficacy compared with a voice-call smoking
      cessation intervention. The study focused on women due to a paucity of studies
      among this population, and women are less likely than men to quit smoking when
      provided with conventional treatment. Methods: Participants in both arms received
      an HIV-tailored smoking cessation intervention comprising eight 30-minute weekly
      counseling sessions in conjunction with active nicotine patches for 8 weeks. The
      only difference between the two arms was the delivery mode of the intervention:
      via either telephone-based video or voice call. Survival analysis and a Cox
      proportional hazard regression model were performed to identify factors
      predicting 6-month prolonged abstinence from smoking. Results: A video-call
      intervention was almost 30% less feasible than a voice-call intervention because
      women in their 50s and 60s or poorer women living in some southern states did not
      have access to video-call equipment. However, those who received the video-call
      intervention were more likely to complete the study than those who had the voice
      call intervention. There was no difference in the acceptability of the two
      interventions. A survival analysis revealed that those in the video arm were
      significantly more likely to maintain smoking abstinence over the 6-month follow
      up period than those in the voice arm (log rank chi 2=4.02, P<0.05). Conclusion:
      Although a video-call intervention is less feasible than a voice-call
      intervention, the former seems to outperform the latter in achieving long-term
      smoking abstinence for women living with HIV, which may offer an advantage over
      establishing therapeutic alliance and visually monitoring their adherence to
      nicotine patches. Clinical trial registration: ClinicalTrials.gov NCT02898597.

PMID- 30288129
TI  - Targeting EGFR and uPAR on human rhabdomyosarcoma, osteosarcoma, and ovarian
      adenocarcinoma with a bispecific ligand-directed toxin.
AB  - Purpose: Human sarcomas are rare and difficult to treat cancerous tumors
      typically arising from soft tissue or bone. Conversely, carcinomas are the most
      common cancer subtype in humans and the primary cause of mortality across all
      cancer patients. While conventional therapeutic modalities can prolong disease
      free intervals and survival in some cases, treatment of refractory or recurrent
      solid tumors is challenging, and tumor-related mortality remains unacceptably
      high. The identification of overexpressed cell surface receptors on sarcoma and
      carcinoma cells has provided a valuable tool to develop targeted toxins as an
      alternative anticancer strategy. Recent investigation of recombinant protein
      linked toxins that specifically target these cancer receptors has led to the
      development of highly specific, cytotoxic, and deimmunized drugs that can kill
      cancer cells. Methods: This study investigated a recombinant protein called
      epidermal growth factor bispecific angiotoxin (eBAT), which is designed to target
      the epidermal growth factor receptor (EGFR) on cancer cells and the urokinase
      plasminogen activator receptor (uPAR) on cancer cells and associated tumor
      vasculature. Both receptors are expressed by a variety of human sarcomas and
      carcinomas. Flow cytometry techniques were used to determine binding affinity of
      eBAT to cancer cells, and proliferation assays were performed to calculate tumor
      killing ability based on half-maximal inhibitory concentrations. Results: eBAT
      demonstrated cytotoxicity against a variety of sarcoma and carcinoma cells that
      overexpress EGFR and uPAR in vitro and showed greater cell killing ability and
      binding affinity to cancer cells compared with its monospecific counterparts.
      Conclusion: The results of our study are promising, and further studies will be
      necessary to confirm the applicability of eBAT as a supplementary therapy for a
      variety of sarcomas, carcinomas, and possibly other refractory malignancies that
      express EGFR and uPAR.

PMID- 30288130
TI  - Using initial serum lactate level in the emergency department to predict the
      sustained return of spontaneous circulation in nontraumatic out-of-hospital
      cardiac arrest patients.
AB  - Objective: To examine the initial level of lactate to predict sustained return of
      spontaneous circulation (ROSC) in nontraumatic out-of-hospital cardiac arrest
      (OHCA) patients. Materials and methods: This was a 30-month retrospective cohort
      study in an emergency department (ED) of a tertiary care hospital. The inclusion
      criteria were adult nontraumatic OHCA patients who came to the ED with ongoing
      chest compression. The primary outcome was initial serum lactate level at the ED
      to predict sustained ROSC in nontraumatic OHCA. Logistic regression was used to
      determine any association between sustained ROSC and significant variables.
      Results: There were 207 patients who met the inclusion criteria. Forty one
      percent of nontraumatic OHCA patients achieved sustained ROSC. The mean +/- SD
      initial serum lactate in the ROSC group was lower than the non-ROSC group (12.0+/
      4.8 vs 12.6+/-5), but without statistical significance. The significant factors
      to predict sustained ROSC were no underlying disease (adjusted odds ratio [aOR]
      1.71, 95% CI 0.51-5.71, P=0.014), cardiac arrest in a public area (aOR 2.40, 95%
      CI 1.2-4.79, P=0.013), and witnessed arrest (aOR 2.39, 95% CI 1.26-4.52,
      P=0.008). The cut-off points of initial serum lactate to predict mortality at 24
      and 48 hours after cardiopulmonary resuscitation were 9.1 (P=0.031) and 9.4
      (P=0.049) mmol/L, respectively. Eleven survived to hospital discharge, and 54.5%
      had good neurological outcome without statistical significance (P=0.553). The
      significant variables and initial lactate levels were used to develop a scoring
      system which ranged from -4 to 11. The receiver operating characters curve
      indicated a cut-off point of 3.6 to predict ROSC with an area under the curve of
      0.715. Conclusion: The initial serum lactate had no association with sustained
      ROSC and hospital discharge with good neurological outcome but can be used to
      predict 24- and 48-hour postresuscitation mortality in nontraumatic OHCA patients
      with initial serum lactate cut-off points of 9.1 and 9.4 mmol/L, respectively.

PMID- 30288131
TI  - Using sideline concussion tests in the emergency department.
AB  - Purpose: Traumatic brain injury (TBI) is a significant cause of death and
      disability in the United States. Many patients with TBI are initially treated in
      the emergency department (ED), but there is no evidence-based method of detecting
      or grading TBI in patients who have normal structural neuroimaging. This study
      aims to evaluate the validity of two common sideline concussion tests. The
      Concussion Symptom Severity Score (CSSS) and modified Balance Error Scoring
      System (mBESS) tests are well-validated sideline tests for concussion, but have
      not been validated in the setting of non-sport-related concussion, in settings
      other than the sideline or athletic training room or in moderate or severe TBI.
      Patients and methods: One hundred forty-eight subjects who had sustained a TBI
      within the previous 72 hours and 53 healthy control subjects were enrolled. CSSS
      and mBESS were administered. Clinical outcomes were followed up prospectively.
      Results: The CSSS was collected in 147 TBI subjects but only 51 TBI subjects were
      able to complete the mBESS. The CSSS was collected for all 53 control subjects,
      and the mBESS was completed for 51 control subjects. The mean CSSS for TBI and
      control subjects was 32.25 and 2.70, respectively (P < 0.001). The average mBESS
      for TBI and control subjects was 7.43 and 7.20, respectively (P = 0.82). CSSS
      greater than 5.17 was 93.43% sensitive and 69.84% specific for TBI. Conclusion:
      The mBESS is poorly tolerated and, among those who can complete the test, not
      sensitive to TBI in the ED. The CSSS is both sensitive to TBI and well tolerated.

PMID- 30288132
TI  - Criteria for self-reported quantitative sleep characteristics of individuals who
      sought medical help for disturbed sleep - a survey of a representative sample of
      the Swedish population.
AB  - Background: The public often seeks rule-of-thumb criteria for good or poor sleep,
      with a particular emphasis on sleep duration, sleep latency, and the number of
      awakenings each night. However, very few criteria are available. Aim: The present
      study sought to identify such criteria. Methods: Whether or not a person has
      sought medical help for sleep problems was selected as an indicator of poor
      sleep. The group that was studied constituted a representative sample of the
      general Swedish population (N=1,128), with a response rate of 72.8%. Results:
      Logistic regression analysis, with an adjustment for age and gender, showed an
      increased OR for a weekday sleep duration of <=6 hour, (OR >2, and for <5 hour:
      OR >6). For weekend sleep, the value was <=6 hour (OR >2). For awakenings per
      night, the critical value was >=2 (OR >2, and for >=5 awakenings: OR >9), and for
      a sleep latency the critical value was >=30 minutes (OR >2, and for >=45 minutes:
      OR >6). Adding difficulties falling asleep and early morning awakening
      (considered qualitative because of the reflected "difficulty"), led to the
      elimination of all the quantitative variables, except for the number of
      awakenings. The addition of "negative effects on daytime functioning" and "sleep
      being a big problem" resulted in the elimination of all the other predictors
      except age. Conclusion: It was concluded that weekday sleep <=6 hour, >=2
      awakenings/night, and a sleep latency of >=30 minutes, can function as criteria
      for poor sleep, but that qualitative sleep variables take over the role of
      quantitative ones, probably because they represent the integration of
      quantitative indicators of sleep.

PMID- 30288133
TI  - Selecting best-suited "patient-related outcomes" in older people admitted to an
      acute geriatric or emergency frailty unit and applying quality improvement
      research to improve patient care.
AB  - The population is aging worldwide, and hospitals are admitting a higher
      proportion of acutely unwell older people. Population-specific factors such as
      multimorbidity and frailty in older people compounded by deficient expertise
      contribute to longer lengths of stay, higher readmission rates, and increased
      rates of institutionalization. A wide range of acute geriatric care models are
      currently providing acute care to frail older people and these have been shown to
      provide a cost-effective high-quality service. In this review, population
      specific factors, service models, and a wide range of patient-related outcomes of
      "at risk" older people admitted to an acute geriatric care unit are explored. In
      addition, we also discuss data measurements and a quality improvement methodology
      to improve the delivery of care based on the patient outcome data. We hope, in
      addition to ensuring effectiveness and sustainability of our current services,
      this may also enhance academic research. Regular monitoring and evaluation of
      patient-related clinical outcomes not only improve the patient care and reduce
      the caregiver burden but also help in implementing quality initiatives to develop
      existing services.

PMID- 30288135
TI  - The attitude of blood donors towards the use of their samples and information in
      biomedical research.
AB  - Introduction: Blood donation is important for saving human life as blood is used
      in surgeries, blood transfusion and for clinical use. The mission of blood banks
      can be extended to include medical research. The objective of the study was to
      determine and assess the attitude of blood donors in Gaza towards the use of
      their blood samples and medical data for biomedical research and the associated
      ethical issues. Methods: The study is cross-sectional and questionnaire-based and
      involved 616 blood donors from the Gaza Strip. Results: The majority of
      participants (86%) showed a positive attitude towards donating blood for medical
      research, including genetic studies. About two-thirds of participants agreed that
      informed consent should be taken before conducting medical research on the
      donated blood. A similar percentage also accepted linking of their health
      information to the donated blood samples. On the other hand, about 38% of
      participants disapproved of sharing of their data with third parties such as
      health insurance companies and health authorities. Finally, 10% of participants
      stated that their future blood donation decision would be affected if they knew
      that part of their donated blood was to be used in research without taking their
      permission. Conclusion: Blood donors in Gaza Strip have a positive attitude
      toward using their donated blood for medical research. More awareness is required
      with respect to the importance of informed consent and access to biomedical
      information.

PMID- 30288134
TI  - Impact of novel antifibrotic therapy on patient outcomes in idiopathic pulmonary
      fibrosis: patient selection and perspectives.
AB  - Patients with idiopathic pulmonary fibrosis, an incurable, progressive fibrotic
      interstitial lung disease, suffer an impaired quality of life due to symptoms,
      resultant functional limitations, and the constraints of supplemental oxygen. Two
      antifibrotic medications, nintedanib and pirfenidone, are approved for the
      treatment of idiopathic pulmonary fibrosis. Both medications slow the rate of
      decline of lung function, but their effect on patient-reported outcomes is not
      yet fully understood. Nintedanib may slow the decline in health-related quality
      of life for treated patients. Pirfenidone may slow the progression of dyspnea and
      improve cough. Patients and providers should participate in shared decision
      making when starting antifibrotic therapy, taking into consideration the benefits
      of treatment in addition to drug-related side effects and dosing schedules.
      Although antifibrotic therapy may have an impact on health-related quality of
      life, providers should also focus on comprehensive care of the patient to improve
      health-related outcomes. This includes a multidisciplinary evaluation, diagnosis
      and treatment of comorbid medical conditions, and referral to and participation
      in a pulmonary rehabilitation program.

PMID- 30288136
TI  - The value of using seasonality and meteorological variables to model intra-urban
      PM2.5 variation.
AB  - A yearlong air monitoring campaign was conducted to assess the impact of local
      temperature, relative humidity, and wind speed on the temporal and spatial
      variability of PM2.5 in El Paso, Texas. Monitoring was conducted at four sites
      purposely selected to capture the local traffic variability. Effects of
      meteorological events on seasonal PM2.5 variability were identified. For
      instance, in winter low-wind and low-temperature conditions were associated with
      high PM2.5 events that contributed to elevated seasonal PM2.5 levels. Similarly,
      in spring, high PM2.5 events were associated with high-wind and low-relative
      humidity conditions. Correlation coefficients between meteorological variables
      and PM2.5 fluctuated drastically across seasons. Specifically, it was observed
      that for most sites correlations between PM2.5 and meteorological variables
      either changed from positive to negative or dissolved depending on the season.
      Overall, the results suggest that mixed effects analysis with season and site as
      fixed factors and meteorological variables as covariates could increase the
      explanatory value of LUR models for PM2.5.

PMID- 30288137
TI  - Bilingual education for young children: review of the effects and consequences.
AB  - Bilingual education has been an educational option in many countries for over 50
      years but it remains controversial, especially in terms of its appropriateness
      for all children. The present review examines research evaluating the outcomes of
      bilingual education for language and literacy levels, academic achievement, and
      suitability for children with special challenges. The focus is on early education
      and the emphasis is on American contexts. Special attention is paid to factors
      such as socioeconomic status that are often confounded with the outcomes of
      bilingual education. The conclusion is that there is no evidence for harmful
      effects of bilingual education and much evidence for net benefits in many
      domains.

PMID- 30288138
TI  - Microfluidic generation of transient cell volume exchange for convectively driven
      intracellular delivery of large macromolecules.
AB  - Efficient intracellular delivery of target macromolecules remains a major
      obstacle in cell engineering and other biomedical applications. We discovered a
      unique cell biophysical phenomenon of transient cell volume exchange by using
      microfluidics to rapidly and repeatedly compress cells. This behavior consists of
      brief, mechanically induced cell volume loss followed by rapid volume recovery.
      We harness this behavior for high-throughput, convective intracellular delivery
      of large polysaccharides (2000 kDa), particles (100 nm), and plasmids while
      maintaining high cell viability. Successful proof of concept experiments in
      transfection and intracellular labeling demonstrated potential to overcome the
      most prohibitive challenges in intracellular delivery for cell engineering.

PMID- 30288139
TI  - Lanthanide DO3A-tropone complexes: efficient dual MR/NIR imaging probes in
      aqueous medium.
AB  - In this work, we describe a novel DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid) based ligand with a chromophoric tropone coordinating sidearm
      (1). Ln3+ complexes of 1 have one inner sphere water molecule. The r1 relaxivity
      of Gd1 is similar to that of the commercial Gd-based MRI agents. The neutral O
      donor atom of the tropone moiety slows down the water exchange rate by a factor
      of 3 compared to GdDOTA. In addition, Nd1 and Yb1 complexes exhibit significant
      NIR emission in aqueous solutions indicating that the tropone unit is an
      efficient sensitizer for these Ln3+-ions. Therefore, this new ligand is a
      promising platform for the design of Ln3+ based dual MR/optical imaging probes.

PMID- 30288140
TI  - Management Options for Nocturia.

PMID- 30288141
TI  - Infertility in Patients With Klinefelter Syndrome: Optimal Timing for Sperm and
      Testicular Tissue Cryopreservation.
AB  - Male factor infertility is a complex issue presenting many diagnostic and
      management challenges. It is responsible for about 50% of all causes of
      infertility and thus carries significant medical, financial, and psychological
      implications for the couples struggling with conception. Klinefelter syndrome is
      the most common chromosomal male anomaly associated with male infertility. This
      review focuses specifically on non-obstructive azoospermia secondary to
      Klinefelter syndrome and discusses controversies surrounding fertility management
      in patients with this genetic disorder.

PMID- 30288142
TI  - Effectiveness of Subcutaneously Administered Leuprolide Acetate to Achieve Low
      Nadir Testosterone in Prostate Cancer Patients.
AB  - Evidence suggests lower nadir testosterone levels during the first year of
      androgen deprivation therapy improve advanced prostate cancer clinical outcomes.
      We evaluated pivotal trials for subcutaneously administered leuprolide acetate (1
      , 3-, 4-, and 6-month doses) to determine nadir testosterone levels. Pooled
      analysis showed 99%, 97%, and 91% of patients reached nadir testosterone <=20,
      <=10, and <=5 ng/dL respectively (median <=3 ng/dL). Across all available
      categories, $88% of patients reached nadir testosterone <=5 ng/dL, and <3%
      experienced a microsurge. Achievement and maintenance of low nadir testosterone
      levels may improve progression-free survival and time to onset of castrate
      resistant prostate cancer.

PMID- 30288143
TI  - Balancing Confounding and Generalizability Using Observational, Real-world Data:
      17-gene Genomic Prostate Score Assay Effect on Active Surveillance.
AB  - Randomized, controlled trials can provide high-quality, unbiased evidence for
      therapeutic interventions but are not always a practical or viable study design
      for certain healthcare decisions, such as those involving prognostic or
      predictive testing. Studies using large, real-world databases may be more
      appropriate and more generalizable to the intended target population of
      physicians and patients to answer these questions but carry potential for hidden
      bias. We illustrate several emerging methods of analyzing observational studies
      using propensity score matching (PSM) and coarsened exact matching (CEM). These
      advanced statistical methods are intended to reveal a "hidden experiment" within
      an observational database, and so refute or confirm a potential causal effect of
      assignment to an intervention and study outcome. We applied these methods to the
      OptumTM Research Database (ORD; Eden Prairie, MN) of electronic health records
      and administrative claims data to assess the effect of the 17-gene Genomic
      Prostate Score(r) (GPSTM; Genomic Health, Redwood City, CA) assay on use of
      active surveillance (AS). In a traditional multivariable logistic regression, the
      GPS assay increased the use of AS by 29% (95% CI, 24%-33%). Upon applying the
      matching methods, the effect of the GPS assay on AS use varied between 27% and
      80% and the matched data were significant among all algorithms. All matching
      algorithms performed well in identifying matched data that improved the imbalance
      in baseline covariates. By using different matching methods to assess causal
      inference in an observational database, we provide further confidence that the
      effect of the GPS assay on AS use is statistically significant and unlikely to be
      a result of confounding due to differences in baseline characteristics of the
      patients or the settings in which they were seen.

PMID- 30288144
TI  - Prostate Biopsy Characteristics: A Comparison Between the Pre- and Post-2012
      United States Preventive Services Task Force (USPSTF) Prostate Cancer Screening
      Guidelines.
AB  - To compare prostate cancer (PCa) characteristics diagnosed by prostate biopsy
      (Pbx) in the 3 years before and after the 2012 United States Preventive Services
      Task Force (USPSTF) recommendations for PCa screening, we completed a
      retrospective comparative analysis of 402 sequential PCa patients diagnosed from
      2010 to 2012 (3 years) with 552 PCa patients diagnosed from 2015 to 2017 (3
      years). Data was collected on patient age, race, total number of biopsies
      performed, prostate specific antigen (PSA), Gleason sum score (GSS), and digital
      rectal examination (DRE). The data was analyzed to determine whether the 2012
      USPSTF screening recommendations affected PCa characteristics. Two study groups
      were defined, Group A and Group B, prior to and after the 2012 USPSTF screening
      recommendations, respectively. In Group A (pre- 2012 USPSTF recommendations), 567
      patients/year underwent a Pbx versus Group B, 398 patients/year, a 30% reduction
      post-USPSTF. The annual positive Pbx rate for Group A is 134/year versus Group B
      184/year, a 37.3% increase post-USPSTF. Group A had high-grade PCa (GSS 7-10) in
      51.5% versus Group B in 60.1%, an 8.6% increase post-USPSTF. In Group B, the
      total number of positive biopsies was increased by 100%. This study shows that in
      Group B, the Pbx rate decreased by 30% but the annual PCa detection rate
      increased by 37%. High-grade GSS (7-10) PCa increased by 8.6%. Despite a
      reduction in the total number of prostate biopsies by 30%, there was a 100%
      increase in the total number of positive prostate biopsies.

PMID- 30288146
TI  - Member Census Shows LUGPA Practices Exhibit High Level of Innovation,
      Sophistication, and Growth.

PMID- 30288148
TI  - Active Surveillance for Prostate Cancer.

PMID- 30288147
TI  - Best of the 2018 AUA Annual Meeting.

PMID- 30288149
TI  - Testicular Torsion.

PMID- 30288145
TI  - Botulinum Toxin Use in Neurourology.
AB  - The use of botulinum toxin A (BTX-A) has revolutionized the treatment of
      neurogenic lower urinary tract dysfunction (NLUTD) over the past three decades.
      Initially, it was used as a sphincteric injection for detrusor sphincter
      dyssynergia but now is used mostly as intradetrusor injection to treat neurogenic
      detrusor overactivity (NDO). Its use is supported by high-level-of-evidence
      studies and it has become the gold-standard treatment for patients with NDO
      refractory to anticholinergics. Several novelties have emerged in the use of BTX
      A in neurourology over the past few years. Although onabotulinumtoxinA (BOTOX(r),
      Allergan, Inc., Irvine, CA) remains the only BTX-A for which use is supported by
      large, multicenter, randomized, controlled trials (RCT), and is therefore the
      only one to be licensed in the United States and Europe, a second BTX-A,
      abobotulinumtoxinA (Dysport(r), Ipsen Biopharmaceuticals, Basking Ridge, NJ), is
      also supported by high-level-of-evidence studies. Other innovations in the use of
      BTX-A in neurourology during the past few years include the BTX switch (from
      abobotulinumtoxinA to onabotulinumtoxinA or the opposite) as a rescue option for
      primary or secondary failures of intradetrusor BTX-A injection and refinements in
      intradetrusor injection techniques (number of injection sites, injection into the
      trigone). There is also a growing interest in long-term failure of BTX-A for NDO
      and their management, and a possible new indication for urethral sphincter
      injections.

PMID- 30288150
TI  - Focal Ablation of Prostate Cancer.

PMID- 30288151
TI  - Clinical Relevance of Petit's Triangle: A Forgotten Landmark.
AB  - This rare case details a right-sided hydronephrotic kidney herniated through
      Petit's triangle. Petit's triangle is an anatomical landmark that is usually not
      clinically significant and only alluded to during multiple-choice examinations.
      This case describes the clinical ramification of this area of weakness and allows
      us to revisit and relearn the anatomy, and its relevance in clinical practice.

PMID- 30288152
TI  - Covariance nuclear magnetic resonance methods for obtaining protein assignments
      and novel correlations.
AB  - Protein NMR resonance assignment can be a tedious and error prone process, and it
      is often a limiting factor in biomolecular NMR studies. Challenges are
      exacerbated in larger proteins, disordered proteins, and often alpha-helical
      proteins, owing to an increase in spectral complexity and frequency degeneracies.
      Here, several multi-dimensional spectra must be inspected and compared in an
      iterative manner before resonances can be assigned with confidence. Over the last
      two decades, covariance NMR has evolved to become applicable to protein multi
      dimensional spectra. The method, previously used to generate new correlations
      from spectra of small organic molecules, can now be used to recast assignment
      procedures as mathematical operations on NMR spectra. These operations result in
      multidimensional correlation maps combining all information from input spectra
      and providing direct correlations between moieties that would otherwise be
      compared indirectly through reporter nuclei. Thus, resonances of sequential
      residues can be identified and side-chain signals can be assigned by visual
      inspection of 4D arrays. This review highlights advances in covariance NMR that
      permitted to generate reliable 4D arrays and describes how these arrays can be
      obtained from conventional NMR spectra.

PMID- 30288153
TI  - Image Segmentation, Registration and Characterization in R with SimpleITK.
AB  - Many types of medical and scientific experiments acquire raw data in the form of
      images. Various forms of image processing and image analysis are used to
      transform the raw image data into quantitative measures that are the basis of
      subsequent statistical analysis. In this article we describe the SimpleITK R
      package. SimpleITK is a simplified interface to the insight segmentation and
      registration toolkit (ITK). ITK is an open source C++ toolkit that has been
      actively developed over the past 18 years and is widely used by the medical image
      analysis community. SimpleITK provides packages for many interpreter
      environments, including R. Currently, it includes several hundred classes for
      image analysis including a wide range of image input and output, filtering
      operations, and higher level components for segmentation and registration. Using
      SimpleITK, development of complex combinations of image and statistical analysis
      procedures is feasible. This article includes several examples of computational
      image analysis tasks implemented using SimpleITK, including spherical marker
      localization, multi-modal image registration, segmentation evaluation, and cell
      image analysis.

PMID- 30288154
TI  - Cost Implications of Reactive Versus Prospective Testing for Dihydropyrimidine
      Dehydrogenase Deficiency in Patients With Colorectal Cancer: A Single-Institution
      Experience.
AB  - Background: Severe toxicity is experienced by a substantial minority of patients
      receiving fluoropyrimidine-based chemotherapy, with approximately 20% of these
      severe toxicities attributable to polymorphisms in the DPYD gene. The DPYD codes
      for the enzyme dihydropyrimidine dehydrogenase (DPD) important in the metabolism
      of fluoropyrimidine-based chemotherapy. We questioned whether prospective DPYD
      mutation analysis in all patients commencing such therapy would prove more cost
      effective than reactive testing of patients experiencing severe toxicity.
      Methods: All patients experiencing severe toxicity from fluoropyrimidine-based
      chemotherapy for colorectal cancer in an Irish private hospital over a 3-year
      period were tested for 4 DPYD polymorphisms previously associated with toxicity.
      The costs associated with an index admission for toxicity in DPD-deficient
      patients were examined. A cost analysis was undertaken comparing the anticipated
      cost of implementing screening for DPYD mutations versus current usual care. One
      way sensitivity analysis was conducted on known input variables. An alternative
      scenario analysis from the perspective of the Irish health-care payer
      (responsible for public hospitals) was also performed. Results: Of 134 patients
      commencing first-line fluoropyrimidine chemotherapy over 3 years, 30 (23%)
      patients developed grade 3/4 toxicity. Of these, 17% revealed heterozygote DPYD
      mutations. The cost of hospitalization for the DPYD-mutated patients was ?232
      061, while prospectively testing all 134 patients would have cost ?23 718.
      Prospective testing would result in cost savings across all scenarios.
      Conclusions: The cost of hospital admission for severe chemotherapy-related
      toxicity is significantly higher than the cost of prospective DPYD testing of
      each patient commencing fluoropyrimidine chemotherapy.

PMID- 30288156
TI  - Pharmacokinetic Equivalence of the High Dose Strength Fixed-Dose Combination
      Tablet of Gemigliptin/Metformin Sustained Release (SR) and Individual Component
      Gemigliptin and Metformin XR Tablets in Healthy Subjects.
AB  - Background: In type 2 diabetes mellitus therapy, fixed-dose combination (FDC) can
      offer not only benefits in glucose control via the combined use of agents, but
      also increase patient compliance. The aim of this study was to assess the
      pharmacokinetic equivalence of the high dose of the FDC tablet
      (gemigliptin/metformin sustained release [SR] 50/1,000 mg) and a corresponding co
      administered dose of individual tablets. Methods: This study was randomized, open
      label, single dose, two treatments, two-period, crossover study, which included
      24 healthy subjects. Subjects received the FDC or individual tablets of
      gemigliptin (50 mg) and metformin XR (1,000 mg) in each period. Geometric mean
      ratios (GMRs) and 90% confidence intervals (CIs) of maximum plasma concentration
      (Cmax) and area under the plasma concentration-time curve from time zero to the
      time of the last quantifiable concentration (AUClast) of the FDC tablet and co
      administration of individual tablet for both gemigliptin and metformin were
      calculated. Results: The GMRs (FDC tablets/co-administration; 90% CIs) for Cmax
      and AUClast of gemigliptin were 1.079 (0.986-1.180) and 1.047 (1.014-1.080),
      respectively. For metformin, the GMRs for Cmax, and AUClast were 1.038 (0.995
      1.083) and 1.041 (0.997-1.088), respectively. The 90% CIs for GMRs of Cmax and
      AUClast for gemigliptin and metformin fell entirely within bounds of 0.800-1.250.
      Both administration of FDC tablet and co-administration of individual tablets
      were well tolerated. Conclusion: FDC tablet exhibited pharmacokinetic equivalence
      and comparable safety and tolerability to co-administration of corresponding
      doses of gemigliptin and metformin XR as individual tablets. Trial registry at
      ClinicalTrials.gov, NCT02056600.

PMID- 30288155
TI  - Proton Pump Inhibitor Use is Associated With Risk of Pancreatic Cancer: A Nested
      Case-Control Study.
AB  - Purpose: To investigate the use of proton pump inhibitors (PPIs) and the risk of
      pancreatic cancer. Methods: A nested case-control analysis was conducted.
      Patients with pancreas cancer were matched with controls by propensity score.
      Univariate and multivariate logistic regression models were used to determine
      whether PPIs use affected the risk of pancreas cancer. Dose effect was analyzed
      based on the cumulative defined daily dose (DDD), which was calculated using the
      total supply of PPIs to individual patients in terms of days and quantity.
      Results: A total of 1087 patients with pancreas cancer were matched with 1087
      control patients from the database. The overall adjusted odds ratio (OR) of PPI
      use associated with pancreas cancer was 1.69 (95% confidence interval [CI], 1.44
      2.05). Dose analysis by cumulative DDD, based on all types of PPI combined,
      revealed a lower adjusted OR of 0.92 (95% CI, 0.64-1.33) for those on <30
      cumulative DDD compared with those on >=150 cumulative DDD, whose adjusted OR was
      2.19 (95% CI, 1.68-2.85). Compared with PPI nonusers, the risks of pancreas
      cancer were: OR 0.89 (95% CI, 0.62-1.27) for patients using PPI <30 days and 2.22
      (95% CI, 1.68-2.94) for >=150 days. Conclusions: Risk of pancreas cancer was
      associated with PPI use in patients with peptic ulcer diseases or
      gastroesophageal reflux disease.

PMID- 30288157
TI  - Characteristics of High-Intent Suicide Attempters Admitted to Emergency
      Departments.
AB  - Background: The suicide rate in Korea has been the highest among the Organization
      for Economic Cooperation and Development countries since 2003. However, there is
      a lack of in-depth data regarding the characteristics of suicide attempters.
      Understanding the intent of suicide attempters will help improve the
      effectiveness of suicide prevention strategies. Therefore, to provide a resource
      for developing the necessary interventions, this study aimed to examine the
      differences in suicide-related and clinical variables according to the strength
      of suicidal intent. Methods: The subjects were 328 suicide attempters admitted to
      emergency departments at 5 university hospitals in Daegu-Gyeongbuk province
      between 2011 and 2014. We used various scales to examine suicide-related and
      clinical variables and a structured questionnaire to explore psychosocial
      characteristics. We evaluated suicidal intent using the Pierce Suicide Intent
      Scale and a clinician-rated scale that measured suicidal authenticity. Results:
      Individuals with high suicidal intent were significantly older, had higher
      Hamilton Depression Rating Scale (HDRS) scores, higher rates of premeditation,
      and sustained suicidal ideation. Furthermore, suicide methods, timing, and
      psychiatric treatment histories differed by the strength of subjects' suicidal
      intent. Moreover, multiple logistic regression showed that depressed mood as a
      reason for attempting suicide, premeditation, and higher HDRS scores were
      significantly associated with higher suicidal intent. Conclusion: Depression,
      premeditation, older age, and sustained suicidal ideation were characteristics of
      individuals with high suicidal intent, and it is necessary to evaluate and
      monitor these factors to prevent repeated suicide attempts.

PMID- 30288158
TI  - Treatment Outcomes in Children and Adolescents with Relapsed or Progressed Solid
      Tumors: a 20-year, Single-Center Study.
AB  - Background: By estimating the survival rates and exploring prognostic factors in
      pediatric patients with relapsed or progressed solid tumors, our purpose was to
      generate background data for future studies. Methods: We reviewed the medical
      records of 258 patients with solid tumors who experienced relapse/progression and
      received subsequent salvage treatment between 1996 and 2016. Results: A total of
      60 patients remained progression-free during first-line salvage treatment, while
      the remaining 198 patients experienced relapse/progression again; 149 underwent
      second-line salvage treatment. A total of 76 patients underwent high-dose
      chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), and 44
      patients received allogeneic SCT. The 10-year progression-free survival (PFS) and
      overall survival (OS) from relapse/progression were 18.4% +/- 2.7% and 24.5% +/-
      3.0%, respectively. Survival rates were relatively higher in patients with
      anaplastic ependymoma, initially non-high-risk neuroblastoma, osteosarcoma, Wilms
      tumor and retinoblastoma. A multivariate analysis showed that relapse/progression
      during initial treatment, metastatic relapse/progression, and impossible
      debulking surgery were independent poor prognostic factors for both PFS and OS.
      Patients who exhibited a complete response or partial response during
      conventional salvage treatment showed significantly higher survival after SCT
      than those with stable disease or progressive disease (10-year OS: 54.8% +/- 7.0%
      vs. 7.0% +/- 3.5%, P < 0.001). Conclusion: The prognosis of relapsed/progressed
      pediatric solid tumors still remains unsatisfactory. New, effective treatment
      strategies are needed to overcome limitations of current approaches. Hopefully,
      the background data generated herein will be used in future clinical trials
      involving patients with relapsed/progressed solid tumors.

PMID- 30288159
TI  - Factors Related with Utilizing Hospice Palliative Care Unit among Terminal Cancer
      Patients in Korea between 2010 and 2014: a Single Institution Study.
AB  - Background: Establishing and designating specialized hospice palliative care
      units (HPCUs) has been an important part of national policy to promote hospice
      palliative care in Korea in the recent decade. However, few studies have sought
      to identify patterns and barriers for utilizing HPCU over the period of national
      policy implementation. We aimed to investigate factors related with utilizing
      HPCU for terminal cancer patients after consultation with a palliative care team
      (PCT). Methods: We reviewed medical records for 1,028 terminal cancer patients
      who were referred to the PCT of the National Cancer Center in 2010 and 2014. We
      compared the characteristics of the patients who decided to utilize HPCU and
      those who did not. We also analyzed factors influencing choices for a medical
      institution and reasons for not selecting an HPCU. Results: The patients' mean
      age was 61.0 +/- 12.2, with lung cancer patients (24.3%) comprising the largest
      percentage of these patients. The percentage of referred patients who utilized an
      HPCU was 53.9% in 2014, increasing from 44.6% in 2010. Older age and awareness of
      terminal illness were found to be positively associated with utilization of an
      HPCU. The most common reason for not selecting an HPCU was "refusing hospice
      facility" (34.9%), followed by "near death," "poor accessibility to an HPCU," and
      "caregiving problems." Conclusion: Compared to 2010, HPCU utilization by terminal
      cancer patients increased in 2014. Improving awareness of terminal condition
      among patients and family members and earlier discussion of end-of-life care
      would be important to promote utilization of HPCU.

PMID- 30288160
TI  - Solid Tumors in Children and Adolescents.

PMID- 30288161
TI  - Importance of Identifying Characteristics of High-Intent Suicide Attempters
      Admitted to Emergency Departments.

PMID- 30288162
TI  - Constraining chemical transport PM2.5 modeling outputs using surface monitor
      measurements and satellite retrievals: application over the San Joaquin Valley.
AB  - Advances in satellite retrieval of aerosol type can improve the accuracy of near
      surface air quality characterization by providing broad regional context and
      decreasing metric uncertainties and errors. The frequent, spatially extensive and
      radiometrically consistent instantaneous constraints can be especially useful in
      areas away from ground monitors and progressively downwind of emission sources.
      We present a physical approach to constraining regional-scale estimates of PM2.5,
      its major chemical component species estimates, and related uncertainty estimates
      of chemical transport model (CTM; e.g., the Community Multi-scale Air Quality
      Model) outputs. This approach uses ground-based monitors where available,
      combined with aerosol optical depth and qualitative constraints on aerosol size,
      shape, and light-absorption properties from the Multi-angle Imaging
      SpectroRadiometer (MISR) on the NASA Earth Observing System's Terra satellite.
      The CTM complements these data by providing complete spatial and temporal
      coverage. Unlike widely used approaches that train statistical regression models,
      the technique developed here leverages CTM physical constraints such as the
      conservation of aerosol mass and meteorological consistency, independent of
      observations. The CTM also aids in identifying relationships between observed
      species concentrations and emission sources. Aerosol air mass types over
      populated regions of central California are characterized using satellite data
      acquired during the 2013 San Joaquin field deployment of the NASA Deriving
      Information on Surface Conditions from Column and Vertically Resolved
      Observations Relevant to Air Quality (DISCOVER-AQ) project. We investigate the
      optimal application of incorporating 275 m horizontal-resolution aerosol air-mass
      type maps and total-column aerosol optical depth from the MISR Research Aerosol
      retrieval algorithm (RA) into regional-scale CTM output. The impact on surface
      PM2.5 fields progressively downwind of large single sources is evaluated using
      contemporaneous surface observations. Spatiotemporal R 2 and RMSE values for the
      model, constrained by both satellite and surface monitor measurements based on 10
      fold cross-validation, are 0.79 and 0.33 for PM2.5, 0.88 and 0.65 for NO3 -, 0.78
      and 0.23 for SO4 2-, and 1.01 for NH+, 0.73 and 0.23 for OC, and 0.31 and 0.65
      for EC, respectively. Regional cross-validation temporal and spatiotemporal R2
      results for the satellite-based PM2.5 improve by 30 % and 13 %, respectively, in
      comparison to unconstrained CTM simulations and provide finer spatial resolution.
      SO4 2- cross-validation values showed the largest spatial and spatiotemporal R2
      improvement, with a 43 % increase. Assessing this physical technique in a well-
      instrumented region opens the possibility of applying it globally, especially
      over areas where surface air quality measurements are scarce or entirely absent.

PMID- 30288163
TI  - Anti-Mullerian Hormone Levels in Preeclampsia: A Systematic Review of the
      Literature.
AB  - Objective: Serum Anti-Mullerian hormone (AMH) has been implicated in the
      pathogenesis of cardiovascular disease. Its prognostic value in determining the
      risk of developing preeclampsia remains, to date, unclear. The purpose of the
      present systematic review is to accumulate current evidence in this field.
      Materials and methods: We searched Medline (1966-2017), Scopus (2004-2017),
      Clinicaltrials.gov (2008-2017), EMBASE (1980-2017), LILACS (1986-2017) and
      Cochrane Central Register of Controlled Trials CENTRAL (1999-2017) databases.
      Results: Four studies were included in with a total number of 401 women. Among
      them 146 had preeclampsia while 232 were recruited as normotensive controls.
      Current data are suggestive of the potential predictive value of serum AMH as its
      levels seem to be lower among women that develop preeclampsia. One study reported
      that women with and AMH value below the 10th percentile of the studied population
      had a 3.3 increased risk of developing preeclampsia (OR 3.3, 95% CI 1.2-8.7, p =
      0.01). Conclusion: Taking in mind these findings, future studies are needed in
      this field to establish optimal cut-off values and evaluate the specificity and
      sensitivity of this biomarker during the first trimester of pregnancy.

PMID- 30288164
TI  - The Effect of Auriculotherapy on Labor Pain, Length of Active Phase and
      Episiotomy Rate Among Reproductive Aged Women.
AB  - Objective: This study aimed to evaluate the effect of auriculotherapy on labor
      pain, the length of the active phase, and episiotomy rate among reproductive aged
      Iranian women. Materials and methods: In this study, 80 women were assigned to
      two groups: auriculotherapy (n = 40) and control group (n = 40). Auriculotherapy
      was performed in the earlobe in the Zero, Shen Men, Uterus, Pelvic, Abdomen,
      Spleen, External genitalia, and Master cerebral regions in the cervix dilation of
      4, 6, and 8 cm between uterine contractions. The control group received routine
      hospital care. The labor pain, duration of the active phase, and rate of
      episiotomy were assessed in two groups. The independent t- test and chi-square
      were used for statistical purposes. Results: The mean of labor pain during the
      active phase was 7.56 +/- 0.83 in the auriculotherapy group and 8.43 +/- 0.69 in
      the control group (p < 0.001). The length of active phase was significantly lower
      in the auriculotherapy than that in the control group (176.2 +/- 1 min vs.
      342.8+/-87.2 min, p < 0.001). The rate of normal vaginal delivery (without an
      episiotomy or perineal tears) was significantly higher in the auriculotherapy
      group than that in the control group (50% vs. 2.5%, p < 0.001). Conclusion:
      Auriculotherapy is safe, cost effective and devoid of side effects to reduce the
      labour pain, length of the active phase and the rate of episiotomy in nulliparous
      women. This method can be considered as a complementary medicine in labour.

PMID- 30288166
TI  - Evaluation of Feeding Disorders Including Gastro-Esophageal Reflux and
      Oropharyngeal Dysfunction in Children With Cerebral Palsy.
AB  - Objective: This cross sectional study aims to survey developing feeding disorders
      and nutritional deficiencies disorders in children with neurodevelopmental
      disorders such as cerebral palsy. Materials and methods: A total of 50 children
      (28 boys and 22 girls) with cerebral palsy and symptoms suggesting
      gastrointestinal problems such as choking, recurrent pneumonia and poor weight
      gain, who referred to the Pediatric department of Vali-asr Hospital, Imam
      Khomeini hospital complex between 1 October 2012 and 30 October 2013, were
      checked. Motor function classification system was used to classify patient's
      functional gross motor severity. All patients were examined and underwent
      deglutition videofluroscopy (modified barium swallow) and upper GI endoscopy with
      esophageal biopsies. Outcome of this study was the prevalence of oropharyngeal
      incoordination and GERD. Its relationship with some variables like motor and
      cognitive developmental delay were analyzed and p value < 0.05 was considered
      significant. Medical therapy and/or oral physiotherapy and nutritional
      rehabilitation were started. They were examined after 6 months of treatment.
      Decrease in choking and episodes of respiratory infections that needed
      hospitalization and weight gain after 6 months treatment were considered as
      secondary outcomes (response to treatment). Results: Prevalence of GERD was 66%
      and oropharyngeal dysphagia was estimated 82%. According to results of video
      fluroscopy and endoscopic biopsies, 52% of patients were affected by both GERD
      and oropharyngeal dysfunction. The gross motor function disability was the only
      variable that significantly related to the prevalence of feeding disorders (p =
      0.015). Despite nutritional rehabilitation only 46% of children have weight gain.
      Conclusion: Feeding disorders such as GERD and oropharyngeal dysfunction are more
      prevalent in children with cerebral palsy especially in children with severe
      gross motor disabilities. Since, clinical manifestations of these disorders can
      be similar accurate diagnostic methods should be selected for all children with
      cerebral palsy and gastrointestinal symptoms. Treatment should start early to
      reduce the complications and improve outcomes.

PMID- 30288165
TI  - Association of Hypothyroidism and Anti-Thyroid Antibodies With Preterm Delivery:
      A Cross Sectional Study.
AB  - Objective: Preterm delivery is a common and eventful phenomenon with long
      standing complications, heavily burdening the health system. Many risk factors
      have been suggested to increase the likelihood of this event, one being
      hypothyroidism and high levels of anti-thyroid antibodies. The present study
      sought to explore the association between hypothyroidism and anti-thyroid
      antibodies with preterm delivery. Materials and methods: A case control study was
      conducted on 400 patients attending Educational-Medical centers of Urmia
      University of Medical Sciences (Urmia, Iran) between November 2013 and April
      2016, in which 200 patients with term deliveries and 200 patients with preterm
      deliveries were compared for differences in hypothyroidism, existence of anti-
      thyroperoxidase (TPO) antibodies based on blood samples obtained from the
      patients which were tested using chemi-luminescence method. Results: In the group
      of patients with preterm delivery, 85 patients had hypothyroidism (42.5%), and
      from the term delivery group, 67 patients (33.5%) had hypothyroidism, the
      difference was not statistically significant (p = 0.14). But, when groups of
      early and late preterm deliveries were compared in terms of having anti-TPO
      antibodies, there was a significant difference between them, with early preterm
      delivery having 8 patients positive out of 44 patients and late preterm delivery
      having 7 positives out of 141 patients (p = 0.004). Conclusion: Hypothyroidism
      had an insignificant effect on preterm delivery rates, but the existence of anti
      TPO antibodies in the serum had a significant increasing effect on early preterm
      deliveries and could be regarded as a risk factor.

PMID- 30288167
TI  - Perceived Stigma in People Living With HIV in Qom.
AB  - Objective: This study aimed to report on perceived stigma by PLWH and factors
      that affect it. Materials and methods: A cross-sectional study was carried out on
      120 PLWH in Qom, Iran from November 2015 to April 2016. Persian version of Fife
      and Wright's scale was used to measure perceived stigma. Results: The mean score
      of stigma was 73.19 +/- 12.23 (range: 48-97). The means of external stigma and
      internal stigma were 43.70 +/- 8.61 (range: 19-60), and 29.49 +/- 5.32 (range: 17
      40), respectively. Living in a rural areas (beta = 10.341, p = 0.006),
      unemployment status (beta = 6.910, p = 0.006), and poor support from family
      members (beta = 4.772, p = 0.028) significantly increased the level of perceived
      stigma. PLWH experience a considerable level of stigma in their daily life. Mass
      media involvement to increase public awareness and reduce HIV related stigma need
      be more highlighted. Conclusion: Working with the patients' families,
      interventions in the rural areas and workplaces, and providing social supports is
      necessary to minimize the HIV related stigma.

PMID- 30288168
TI  - Pregnant Women's Health Literacy in the South of Iran.
AB  - Objective: Investigate the health literacy of pregnant women in the south of
      Iran. Materials and methods: The present descriptive-analytical study was
      conducted on 775 pregnant women in the south of Iran (including Boushehr, Ahvaz,
      Zahedan and Bandar Abbas cities) through the clustering sample selection method.
      The data were collected through the Test of Functional Health Literacy in Adults:
      TOFHLA, and were analyzed statistically via SPSS 16 through independent-sample t
      test and ANOVA. Results: The average age of the subjects was 31.89 +/- 7.54
      years. The results indicated that 15.5% of the subjects had an inadequate level
      of health literacy; 41.7% had a border-line level of health literacy, and 42.8%
      had an adequate level of literacy. Significant correlations were found between
      each of these variables and the subjects' level of health literacy: education,
      age, occupation and care provision during pregnancy (p ? 0.05). The highest mean
      score of health literacy belonged to Ahvaz while the lowest belonged to Boushehr.
      Conclusion: According to the results, the health literacy level of pregnant women
      in the target geographical areas showed to be inadequate or on a border-line.
      Moreover, subjects' education, age and occupation showed to be significantly
      correlated with health literacy. Therefore, promoting pregnant women's health
      literacy through simplifying health-related information, use of audio-visual
      media, improving communicative skills among the health staff and mothers can be
      effective.

PMID- 30288169
TI  - Relationship Between Pregnancy Complications and Serum Pregnancy Associated
      Plasma-Protein-A and Free-beta-Human Chorionic Gonadotropin in the First
      Trimester Among Iranian Women.
AB  - Objective: To evaluate the relationship between maternal serum levels of
      pregnancy-associated-plasma-protein-A (PAPP-A) and beta-human-chorionic
      gonadotropin (beta-hCG) and pregnancy complications. Materials and methods: This
      is a case-control study conducted during 2015- 2016. Women at their first
      pregnancy were enrolled and serum PAPP-A and free-beta-hCG were measured in 9-14
      weeks of gestation. They were followed till the end of pregnancylooking for
      complications including preterm labor, pregnancy induced hypertension (PIH),
      abortion, and intra-uterine growth retardation (IUGR). Results: A total of 1070
      pregnant women (mean age: 28.64 +/- 4.95 years) were enrolled. Low serum levels
      of PAPP-A were more frequent in patients developing IUGR (17.4% versus 1.2%, p <
      0.001), preterm labor (13% versus 2%, p = 0.013), and PIH (17.4% versus 4%, p =
      0.015) compared those without complications. The serum levels of free-beta-hCG
      were not different in patients with and without complications (p > 0.05).
      Conclusion: There is an association between low serum levels of PAPP-A and
      developing IUGR, preterm labor, and PIH.

PMID- 30288170
TI  - Successful Pregnancy Outcome in Recurrent Ovarian Cancer in a 26 Year Old: A Case
      Report.
AB  - Objective: To report a case of Successful Pregnancy Outcome in Recurrent Ovarian
      Cancer in a 26 year Old. Case Report: A 26 years old primigravida presented in
      antenatal clinic at 23 weeks of pregnancy with recurrence of ovarian cancer of
      mucinous type. Following refusal of surgical management, two courses of single
      dose carboplatin was administered. However, before third cycle of chemotherapy
      could be administered ,there was deranged liver functions tests, following which
      elective Cesarean section with staging laparotomy was planned at 34 weeks for
      breech presentation with oligohydramnios. A live healthy baby girl 2.3kg was
      delivered. Total abdominal hysterectomy with right salpingo-oopherectomy,
      infracolic omentectomy, appendectomy was done. The final diagnosis was recurrent
      mucinous ovarian adenocarcinoma. Postoperatively, she was given six cycles of
      chemotherapy (carboplatin and paclitaxel). Conclusion: Chemotherapy and surgery,
      both are safe beyond first trimester and multidisciplinary treatment must be
      planned after taking into account the wishes of couple.

PMID- 30288171
TI  - The Association Between Dental Anxiety And Psychiatric Disorders And Symptoms: A
      Systematic Review.
AB  - Background: A growing amount of evidence suggests that dental anxiety is
      associated with other psychiatric disorders and symptoms. A systematic review was
      conducted to critically evaluate the studies of comorbidity of dental anxiety
      with other specific phobias and other Axis I psychiatric disorders. Objective:
      The aim of the review was to explore how dental anxiety is associated with other
      psychiatric disorders and to estimate the level of comorbid symptoms in dental
      anxiety patients. Methods: The review was conducted and reported in accordance
      with the MOOSE statement. Data sources included PubMed, PsycInfo, Web of Science
      and Scopus. Results: The search produced 631 hits, of which 16 unique records
      fulfilled the inclusion criteria. The number of eligible papers was low. Study
      populations were heterogeneous including 6,486 participants, and a total of 25
      tests and in few cases clinical interviews were used in the evaluation processes.
      The results enhanced the idea about the comorbidity between dental anxiety and
      other psychiatric disorders. The effect was found strong in several studies.
      Conclusion: Patients with a high level of dental anxiety are more prone to have a
      high level of comorbid phobias, depression, mood disorders and other psychiatric
      disorders and symptoms.

PMID- 30288173
TI  - Genomic and phenotypic characterization of a refactored xylose-utilizing
      Saccharomyces cerevisiae strain for lignocellulosic biofuel production.
AB  - Background: Engineered strains of Saccharomyces cerevisiae have significantly
      improved the prospects of biorefinery by improving the bioconversion yields in
      lignocellulosic bioethanol production and expanding the product profiles to
      include advanced biofuels and chemicals. However, the lignocellulosic biorefinery
      concept has not been fully applied using engineered strains in which either
      xylose utilization or advanced biofuel/chemical production pathways have been
      upgraded separately. Specifically, high-performance xylose-fermenting strains
      have rarely been employed as advanced biofuel and chemical production platforms
      and require further engineering to expand their product profiles. Results: In
      this study, we refactored a high-performance xylose-fermenting S. cerevisiae that
      could potentially serve as a platform strain for advanced biofuels and
      biochemical production. Through combinatorial CRISPR-Cas9-mediated rational and
      evolutionary engineering, we obtained a newly refactored isomerase-based xylose
      fermenting strain, XUSE, that demonstrated efficient conversion of xylose into
      ethanol with a high yield of 0.43 g/g. In addition, XUSE exhibited the
      simultaneous fermentation of glucose and xylose with negligible glucose
      inhibition, indicating the potential of this isomerase-based xylose-utilizing
      strain for lignocellulosic biorefinery. The genomic and transcriptomic analysis
      of XUSE revealed beneficial mutations and changes in gene expression that are
      responsible for the enhanced xylose fermentation performance of XUSE.
      Conclusions: In this study, we developed a high-performance xylose-fermenting S.
      cerevisiae strain, XUSE, with high ethanol yield and negligible glucose
      inhibition. Understanding the genomic and transcriptomic characteristics of XUSE
      revealed isomerase-based engineering strategies for improved xylose fermentation
      in S. cerevisiae. With high xylose fermentation performance and room for further
      engineering, XUSE could serve as a promising platform strain for lignocellulosic
      biorefinery.

PMID- 30288172
TI  - Association between chronological depressive changes and physical symptoms in
      postoperative pancreatic cancer patients.
AB  - Background: Pancreatic cancer (PC) has poorer prognosis and higher surgical
      invasiveness than many other cancers, with associated psychiatric symptoms
      including depression and anxiety. Perioperative depression has not been
      investigated in PC patients regarding surgical stress and relevant interventions.
      Methods: We evaluated chronological depressive changes and subjective physical
      symptoms in surgically treated PC patients preoperatively and at 3 and 6 months
      postoperatively.Enrolled patients undergoing pancreatic tumor surgery completed
      questionnaires based on the Self-Rating Depression Scale (SDS) and Functional
      Assessment of Cancer Therapy for Patients with Hepatobiliary Cancer (FACT-Hep)
      preoperatively, and at 3 and 6 months postoperatively. Responses were analyzed
      with JMP(r) Pro using one-way and two-way ANOVA, Spearman's rank correlation
      coefficient, and multiple regression analysis. Results: Malignancy was diagnosed
      in 73 of 101 patients postoperatively; SDS score was significantly higher in
      these patients than in those with benign tumors at all timepoints:
      malignant/benign, 41.8/37.9 preoperatively (p = 0.004); 43.5/37.8 3 months
      postoperatively (p = 0.006); and 42.9/37.7 6 months postoperatively (p = 0.020).
      SDS scores were significantly higher in patients < 65 years old with malignancy
      at 3 months than at 6 months postoperatively (44.6/42.5, p = 0.046) and in
      patients with malignancy who underwent pancreaticoduodenectomy at 3 months
      postoperatively than preoperatively (43.4/41.1; p = 0.028). SDS scores moderately
      correlated with 8 physical symptom-related FACT-Hep items 3 months
      postoperatively (p < 0.05), showing low-to-moderate correlation with 16 physical
      symptom-related FACT-Hep items at 6 months postoperatively (p < 0.05). Multiple
      regression analysis of FACT-Hep symptoms significantly correlated with SDS scores
      revealed the following significant variables: "lack of energy" (p < 0.000) and
      "pain" (p = 0.018) preoperatively (R2 = 0.43); "able to perform usual activities"
      (p = 0.031) and "lack of energy" (p < 0.000) at 3 months postoperatively (R2 =
      0.51); and "stomach swelling or cramps" (p = 0.034) and "bowel control" (p =
      0.049) at 6 months postoperatively (R2 = 0.52). Conclusions: PC patients
      experience persistently high levels of depression preoperatively through 6 months
      postoperatively, with associated subjective symptoms including pain and
      gastrointestinal symptoms. Trial registration: UMIN Clinical Trials Registry
      000009592, Registered 20 December 2012.

PMID- 30288174
TI  - Lignin-carbohydrate complexes: properties, applications, analyses, and methods of
      extraction: a review.
AB  - The complexity of lignin and hemicellulose segmentation has been known since the
      middle of the ninetieth century. Studies confirmed that all lignin units in
      coniferous species and 47-66% of lignin moieties in deciduous species are bound
      to hemicelluloses or cellulose molecules in lignin-carbohydrate complexes (LCC).
      Different types and proportions of lignin and polysaccharides present in biomass
      lead to the formation of LCC with a great variety of compositions and structures.
      The nature and amount of LCC linkages and lignin substructures affect the
      efficiency of pulping, hydrolysis, and digestibility of biomass. This review
      paper discusses the structures, compositions, and properties of LCC present in
      biomass and in the products obtained via pretreating biomass. Methods for
      extracting, fractionating, and analyzing LCC of biomass, pulp, and spent pulping
      liquors are critically reviewed. The main perspectives and challenges associated
      with these technologies are extensively discussed. LCC could be extracted from
      biomass following varied methods, among which dimethyl sulfoxide or dioxane
      (Bjorkman's) and acetic acid (LCC-AcOH) processes are the most widely applied.
      The oxidation and methylation treatments of LCC materials elucidate the locations
      and frequency of binding sites of hemicelluloses to lignin. The two-dimensional
      nuclear magnetic resonance analysis allows the identification of the structure
      and the quantity of lignin-carbohydrate bonds involved in LCC. LCC application
      seems promising in medicine due to its high anti-HIV, anti-herpes, and anti
      microbial activity. In addition, LCC was successfully employed as a precursor for
      the preparation of spherical biocarriers.

PMID- 30288176
TI  - Microbial temperature sensitivity and biomass change explain soil carbon loss
      with warming.
AB  - Soil microorganisms control carbon losses from soils to the atmosphere1-3, yet
      their responses to climate warming are often short-lived and unpredictable4-7.
      Two mechanisms, microbial acclimation and substrate depletion, have been proposed
      to explain temporary warming effects on soil microbial activity8-10. However,
      empirical support for either mechanism is unconvincing. Here we used geothermal
      temperature gradients (> 50 years of field warming)11 and a short-term experiment
      to show that microbial activity (gross rates of growth, turnover, respiration and
      carbon uptake) is intrinsically temperature sensitive and does not acclimate to
      warming (+ 6 oC) over weeks or decades. Permanently accelerated microbial
      activity caused carbon loss from soil. However, soil carbon loss was temporary
      because substrate depletion reduced microbial biomass and constrained the
      influence of microbes over the ecosystem. A microbial biogeochemical model12-14
      showed that these observations are reproducible through a modest, but permanent,
      acceleration in microbial physiology. These findings reveal a mechanism by which
      intrinsic microbial temperature sensitivity and substrate depletion together
      dictate warming effects on soil carbon loss via their control over microbial
      biomass. We thus provide a framework for interpreting the links between
      temperature, microbial activity and soil carbon loss on timescales relevant to
      Earth's climate system.

PMID- 30288175
TI  - Neck circumference and its association with cardiometabolic risk factors: a
      systematic review and meta-analysis.
AB  - Background: Recently, neck circumference (NC) has been used to predict the risk
      of cardiometabolic factors. This study aimed to perform a systematic review and
      meta-analysis to examine: (i) the sensitivity (SE) and specificity (SP) of NC to
      predict cardiometabolic risk factors and (ii) the association between NC and the
      risk of cardiometabolic parameters. Methods: A systematic search was conducted
      through PubMed/Medline, Institute of Scientific Information, and Scopus, until
      2017 based on the search terms of metabolic syndrome (MetS) and cardio metabolic
      risk factors. Random-effect model was used to perform a meta-analysis and
      estimate the pooled SE, SP and correlation coefficient (CC). Results: A total of
      41 full texts were selected for systematic review. The pooled SE of greater NC to
      predict MetS was 65% (95% CI 58, 72) and 77% (95% CI 55, 99) in adult and
      children, respectively. Additionally, the pooled SP was 66% (95% CI 60, 72) and
      66% (95% CI 48, 84) in adult and children, respectively. According to the results
      of meta-analysis in adults, NC had a positive and significant correlation with
      fasting blood sugar (FBS) (CC: 0.16, 95% CI 0.13, 0.20), HOMA-IR (0.38, 95% CI
      0.25, 0.50), total cholesterol (TC) (0.07 95% CI 0.02, 0.12), triglyceride (TG)
      concentrations (0.23, 95% CI 0.19, 0.28) and low density lipoprotein cholesterol
      (LDL-C) (0.14, 95% CI 0.07, 0.22). Among children, NC was positively associated
      with FBS (CC: 0.12, 95% CI 0.07, 0.16), TG (CC: 0.21, 95% CI 0.17, 0.25), and TC
      concentrations (CC: 0.07, 95% CI 0.02, 0.12). However, it was not significant for
      LDL-C. Conclusion: NC has a good predictive value to identify some
      cardiometabolic risk factors. There was a positive association between high NC
      and most cardiometabolic risk factors. However due to high heterogeneity,
      findings should be declared with caution.

PMID- 30288177
TI  - Effect of spatial heterogeneity and colocalization of eNOS and capacitative
      calcium entry channels on shear stress-induced NO production by endothelial
      cells: A modeling approach.
AB  - Introduction: Colocalization of endothelial nitric oxide synthase (eNOS) and
      capacitative Ca2+ entry (CCE) channels in microdomains such as cavaeolae in
      endothelial cells (ECs) has been shown to significantly affect intracellular Ca2+
      dynamics and NO production, but the effect has not been well quantified. Methods:
      We developed a two-dimensional continuum model of an EC integrating shear stress
      mediated ATP production, intracellular Ca2+ mobilization, and eNOS activation to
      investigate the effects of spatial colocalization of plasma membrane eNOS and CCE
      channels on Ca2+ dynamics and NO production in response to flow-induced shear
      stress. Our model examines the hypothesis that subcellular colocalization of
      cellular components can be critical for optimal coupling of NO production to
      blood flow. Results: Our simulations predict that heterogeneity of CCE can result
      in formation of microdomains with significantly higher Ca2+ compared to the
      average cytosolic Ca2+. Ca2+ buffers with lower or no mobility further enhanced
      Ca2+ gradients relative to mobile buffers. Colocalization of eNOS to CCE channels
      significantly increased NO production. Conclusions: Our results provide
      quantitative understanding for the role of spatial heterogeneity and the
      compartmentalization of signals in regulation of shear stress-induced NO
      production.

PMID- 30288178
TI  - Co-Administration of Fish Oil With Signal Transduction Inhibitors Has Anti
      Migration Effects in Breast Cancer Cell Lines, in vitro.
AB  - Background: There is an urgent need for new therapies to treat cancer metastasis.
      Fish oil, with high omega 3 fatty acid content, has shown anticancer activity and
      signal transduction inhibitors have shown anti-metastatic properties. Objective:
      To provide preliminary in vitro data on the anti-migration potential of signal
      transduction inhibitors and co-administered fish oil. Methods: MCF-7, TamR and
      FasR breast cancer cell lines were used to determine the effects of combinations
      of PD98059, LY294002 and fish oil in growth assays. Modulations of p-Src and COX
      2, both mediators of motility and invasion, were then determined by Western
      blotting and IHC to ascertain effects on migration potential. Results: Migration
      rates for the three cell lines examined were ranked: FasR>TamR>MCF-7 (p <0.05).
      Addition of fish oil reduced the number of TamR cells migrating after 48h (p
      <0.05), while the addition of PD98059 and LY294002 also decreased migratory
      potential of TamR cells (p <0.05). Addition of PD98059 and LY294002 to TamR cells
      did not result in a significant decrease in p-Src levels; as was the case when
      PD98059, LY294002 and 4-hydroxytamoxifen were added to MCF-7 cells. However, the
      co-administration of fish oil markedly reduced p-Src and COX-2 expression in both
      cell lines. Conclusion: Co-administration of a commercial fish oil with signal
      transduction inhibitors results in decreased cell migration via an unknown co
      operative mechanism and could constitute a novel approach for the treatment of
      breast cancer metastasis.

PMID- 30288179
TI  - Bacterial Biofilm Inhibition in the Development of Effective Anti-Virulence
      Strategy.

PMID- 30288180
TI  - Hemodynamic Effects of the Light Stabilizer Tinuvin 770 in Dogs In Vivo.
AB  - Introduction: Tinuvin 770 [bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate, Ciba
      Geigy, Basel, Switzerland] is a UV light stabilizer that is a component of many
      plastic materials used world-wide in the medical and food industries. We report
      on the acute hemodynamic effects of Tinuvin 770 examined in dogs. Materials and
      Methods: Tinuvin 770 was dissolved in a mixture of saline and ethanol (1:1 v/v)
      and was administered to 12 intravenously narcotized and respirated dogs in
      increasing doses (T1-T7: 1, 3.3, 6.6, 10, 33.3, 66.6 and 100 mg, respectively).
      The doses were given as bolus injections over a three minute period, and the
      effects were recorded for 12 minutes. The vehicle was used as a control.
      Hemodynamic parameters (heart rate, blood pressure, end-diastolic pressure,
      dp/dt, cardiac output) and ECG were monitored continously. Results: At doses T1
      T4, systolic and diastolic blood pressures, mean pressure and ventricular
      contractility were significantly decreased without significant changes in cardiac
      output, heart rate, or PQ interval. At doses T5 and T6, declines in blood
      pressure and myocardial contractility were observed. At doses T6 and T7, heart
      rate and PQ interval decreased substantially. Irreversible circulatory failure
      occured in one dog after administering dose T6 and in 8 dogs following dose T7.
      Conclusion: Tinuvin 770 induces acute hemodynamic alterations. In lower doses, it
      causes peripheral vasodilatation, however at higher doses acute cardiac failure
      occured. Plastics containing Tinuvin 770 should be used with care in medical
      practice and the laboratory.

PMID- 30288182
TI  - Performance of Cone Beam Computed Tomography Systems in Visualizing the Cortical
      Plate in 3D Image Reconstruction: An In Vitro Study.
AB  - Introduction: Cortical bone is an important anatomical structure and its
      thickness needs to be determined prior to many dental procedures to ensure
      treatment success. Imaging modalities are necessarily used in dentistry for
      treatment planning and dental procedures. Three-dimensional image reconstruction
      not only provides visual information but also enables accurate measurement of
      anatomical structures; thus, it is necessarily required for maxillofacial
      examination and in case of skeletal problems in this region. Aims: This study
      aimed to assess the ability of three Cone Beam Computed Tomography (CBCT) systems
      including Cranex 3D, NewTom 3G and 3D Promax for Three-Dimensional (3D) image
      reconstruction of the cortical plate with variable thicknesses. Methods:
      Depending on the cortical bone thickness, samples were evaluated in three groups
      of <= 0. 5 mm, 0.6 -1 mm and 1.1-1.5 mm cortical bone thickness. The CBCT scans
      were obtained from each sample using three systems, their respective FOVs, and 3D
      scans were reconstructed using their software programs. Two observers viewed the
      images twice with a two-week interval. The ability of each system in the 3D
      reconstruction of different thicknesses of cortical bone was determined based on
      its visualization on the scans. The data were analyzed using SPSS and Kappa test.
      Results: The three systems showed the greatest difference in the 3D
      reconstruction of cortical bone with < 0.5 mm thickness. Cranex 3D with 4*6 cm2
      FOV had the highest and 3D Promax with 8*8 cm2 FOV had the lowest efficacy for 3D
      reconstruction of cortical bone. Cranex 3D with 4*6 cm2 and 6*8 cm2 FOVs and
      NewTom 3G with 5*5 cm2 and 8*5 cm2 FOVs showed significantly higher efficacy for
      3D reconstruction of cortical bone with 0.6-1mm thickness while 3D Promax
      followed by NewTom 3G with 8*8 cm2 FOV had the lowest efficacy for this purpose.
      Conclusion: Most CBCT systems have high efficacy for 3D image reconstruction of
      cortical bone with thicknesses over 1 mm while they have poor efficacy for image
      reconstruction of cortical bone with less than 0.5 mm thickness. Thus, for
      accurate visualization of anatomical structures on CBCT scans, systems with
      smaller FOVs and consequently smaller voxel size are preferred.

PMID- 30288183
TI  - Concerns of a Pediatric Dentist in Dental Stem Cells: An Overview.
AB  - Stem cell biology has become an essential part of regenerative medicine and
      dentistry. The fact of availability of these stem cells among various dental
      tissues has doubled the researcher's enthusiasm in the recent years due to fewer
      ethical constraints and minimally invasive nature. Stem cells from deciduous
      tooth among the dental stem cells are the ones obtained with least or no trauma.
      To date, enormous research has been reported on dental stem cells. The purpose of
      this review is to focus only on certain aspects of dental stem cells that are
      important to the specialty of pedodontics. Thus, a detailed emphasis is given on
      stem cells obtained from human deciduous teeth including their harvesting and
      storage techniques.

PMID- 30288181
TI  - Clinical Efficacy in Relieving Dentin Hypersensitivity of Nanohydroxyapatite
      containing Cream: A Randomized Controlled Trial.
AB  - Objective: The study aimed to investigate the effectiveness of Apadent Pro
      (Sangi) Nanohydroxyapatite (nHAP) dental cream to relieve Dentin Hypersensitivity
      (DHS), compared with a positive control cream containing 20% pure silica
      (Silica). Methods: In this double-blind, randomized, parallel-group clinical
      trial, patients diagnosed with DHS and qualified to participate were randomized
      into two groups, nHAP (n=25) and Silica (n=26). Subjects' baseline and
      posttreatment sensitivity were assessed using two pain scales, a four-point
      Dental Pain Scale (DPS) followed by a linear Visual Analog Scale (VAS), after the
      application of ice-cold and air stimuli. Subjects used custom-fabricated trays to
      apply their respective cream for 5 minutes once daily following brushing with
      standard fluoride toothpaste. Posttreatment sensitivity (efficacy) was assessed
      every 2 weeks for 8 weeks. Mean treatment outcomes (percentage change from
      baseline) at each time point were compared using the Tukey HSD test for
      multiplicity (P<0.05). Results: With either air or cold stimulus, VAS and DPS
      indicated a significant (P<0.001) reduction in DHS at each time point with either
      nHAP or Silica. Comparing pain scales, VAS showed no significant difference in
      DHS reduction between the products with either air or cold. However, with DPS,
      DHS reduction was significantly (P<0.05) better with Silica than with nHAP at all
      time points with cold, and at 2, 4, and 8 weeks with air. Conclusion: Both
      Apadent Pro nHAP and Silica dental creams are effective at promoting the relief
      of DHS symptoms. When comparing the efficacy of the two compounds to relieve DHS,
      results of the two pain scales were conflicting.

PMID- 30288184
TI  - Non-Antimicrobial Drugs: Etodolac as a Possible Antimicrobial or Adjuvant Agent
      Against ESKAPE Pathogens.
AB  - Introduction: Multiple-drug resistant bacteria are emerging exponentially in
      healthcare units, threatening public health and requiring novel therapeutic
      approaches. In 2017, World Health Organization published a list that frames
      antimicrobial resistant bacteria into priority levels for research of novel drugs
      to fight them. Methods & Materials: Antimicrobial resistant ESKAPE (Enterococcus
      faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii,
      Pseudomonas aeruginosa, Enterobacter sp.) and Enterococcus faecalis and
      Escherichia coli pathogens are present in this list. Representative isolates of
      each species were used to test the Antibacterial and anti-biofilm formation
      activities of Etodolac (a Non-Steroidal Anti-Inflammatory Drug, NSAID) at 10 and
      1 mM using a broth microdilution technique. Results & Discussion: Statistically
      significant (p< 0,05) results were observed against all tested gram-positives,
      particularly anti-biofilm activity against E. faecium. Etodolac had an almost
      null influence on tested gram-negatives, with the exception of one A. baumannii
      clinical isolate regarding biofilm formation inhibition. Observed differences
      deserve further analysis and prospection of the involved mechanisms, to unravel
      possible novel bacterial targets for drug development. Similar work with other
      NSAID's may also be worth exploring to ascertain novel therapeutic applications
      for these drugs, particularly regarding biofilm formation inhibition, per si or
      as adjuvants of current antibiotherapy, mainly against gram-positives, as
      suggested by present work. Conclusion: Already approved drugs in terms of
      pharmacokinetics and safety may deploy faster solutions for antimicrobial therapy
      against priority pathogens. Current work intends to bring attention to that
      possibility, particularly regarding NSAIDs, anti-biofilm formation and top
      priority pathogens.

PMID- 30288185
TI  - Cadmium Removal from Aqueous Solutions by Strain of Pantoea agglomerans UCP1320
      Isolated from Laundry Effluent.
AB  - Background: Cadmium (Cd), which is a deadly heavy metal of work-related and
      environmental concern, has been recognized as a substance that is teratogenic and
      carcinogenic for humans. Therefore, the need to develop low-cost adsorbents to
      remove heavy metals from aqueous solution has greatly increased. Adsorbents such
      as Pantoea agglomerans biomass have been used. Aims: We investigated the
      biotechnological potential of Pantoea agglomerans for the biosorption of cadmium
      from aqueous solution. Patients and Methods: Pantoea agglomerans UCP1320 isolated
      from the effluent of a laundry industry was used to remove cadmium from aqueous
      solutions. Two approaches were compared using active or thermally inactivated
      biomass. Three different cadmium concentrations of 1, 10 and 100 ppm were used
      under constant stirring at temperatures of 25 degrees C and 35 degrees C as was
      pH of 3.0, 5.0 and 7.0. Variable incubation times of 1, 6, and 24h were also
      studied. Results: The results showed that the temperature did not influence the
      uptake of metal by living cells nor by inactive bacterial biomass. However,
      increasing the pH had a positive effect on removing intermediate concentrations
      of cadmium. Low concentrations of cadmium were completely removed by both live
      and inactive biomass. Conclusion: Pantoea agglomerans biomass was shown to have a
      promising performance for the biotechnological removal of cadmium which had been
      dissolved in aqueous solution.

PMID- 30288188
TI  - SLE and Serum Complement: Causative, Concomitant or Coincidental?

PMID- 30288186
TI  - Composition of Intestinal Microbiota in Two Lines of Rainbow Trout (Oncorhynchus
      Mykiss) Divergently Selected for Muscle Fat Content.
AB  - Background: Recently, studies suggest that gut microbiota contributes to the
      development of obesity in mammals. In rainbow trout, little is known about the
      role of intestinal microbiota in host physiology. Objective: The aim of this
      study was to investigate the link between intestinal microbiota and adiposity, by
      high-throughput 16S RNA gene based illumina Miseq sequencing in two rainbow trout
      lines divergently selected for muscle lipid content. Fish from these two lines of
      rainbow trout are known to have a differing lipid metabolism. Methods: Samples
      from the two lines (L for lean and F for fat) were collected from Midgut (M) and
      Hindgut (H) in juvenile fish (18 months) to compare intestinal microbiota
      diversity. Results: Whatever the lines and intestinal localisation,
      Proteobacteria, Firmicutes and Actinobacteria are the dominant phyla in the
      bacterial community of rainbow trout (at least 97%). The results indicate that
      richness and diversity indexes as well as bacterial composition are comparable
      between all groups even though 6 specific OTUs were identified in the intestinal
      microbiota of fish from the fat line and 2 OTUs were specific to the microbiota
      of fish from the lean line. Our work contributes to a better understanding in
      microbial diversity in intestinal microbiota of rainbow trout. Conclusion:
      Altogether, our study indicates that no major modification of the intestinal
      microbiota is induced by selection for muscle lipid content and associated
      metabolic changes. Finally, we identified members of core microbiota in rainbow
      trout.

PMID- 30288189
TI  - Intramuscular Myxoma in the Supinator Muscle with Transient Postoperative
      Posterior Interosseous Nerve Palsy: A Case Report.
AB  - Background: Intramuscular myxomas are rare, benign mesenchymal tumors in the
      musculoskeletal system, and usually, the tumors arise in the large muscles of the
      thigh, buttocks, shoulder, and upper arm. However, a tumor of the forearm is very
      rare. Herein, we describe the case of an intramuscular myxoma in the supinator
      muscle of a 56-year-old female patient. Case Presentation: Magnetic resonance
      imaging showed a well-defined mass that was hypointense with the peritumoral fat
      ring sign. The differential diagnoses might have been myxoma, schwannoma, or
      intramuscular hemangioma. The histopathological image showed abundant myxoid
      tissue, hypocellularity, and poor vascularization. The cells of the tumor were
      spindle and stellate-shaped with normochromic nuclei. Based on these findings,
      the pathological diagnosis was an intramuscular myxoma. After excising the tumor,
      the patient had transient posterior interosseous nerve palsy. Conclusion: This
      tumor is curative by resection in toto; however, when the tumor exists in the
      forearm, surgeons should be careful to avoid damaging surrounding tissues because
      the tumor is very hard and relatively large compared to the forearm.

PMID- 30288190
TI  - A Protocol for the Management of the Inpatient Fracture Neck of Femur is
      Required.
AB  - Falls within a hospital environment are a major cause of morbidity and may even
      lead to mortality. Pathways for patients suffering a Fractured Neck of Femur
      (FNOF) in the community are well established following the development of the
      Blue Book, BOAST guidelines and National Hip Fracture Database (NHFD). However,
      there is no such agreed pathway for patients suffering FNOF within a hospital
      environment. Such patients have been demonstrated to have a higher risk of delays
      in medical optimisation, delays in operative management, and mortality. There is,
      therefore, a need to create a nationally agreed guideline for the care of the
      "inpatient FNOF" as this is an important subgroup of patients. This article
      highlights this issue as well as advising medical staff on how to identify a
      potential FNOF within a hospital environment in order to ensure prompt management
      of a vulnerable group of patients.

PMID- 30288187
TI  - Losartan, but not Enalapril and Valsartan, Inhibits the Expression of IFN-gamma,
      IL-6, IL-17F and IL-22 in PBMCs from Rheumatoid Arthritis Patients.
AB  - Background: Rheumatoid Arthritis (RA) is a chronic and inflammatory disease that
      affects about 1% of the world's population. Almost 70% of RA patients have a
      cardiovascular disease such as Systemic Arterial Hypertension (SAH). Inflammatory
      cytokines are clearly involved in the pathogenesis of RA and correlated with SAH.
      Objective: It is necessary to understand whether the antihypertensive drugs have
      a dual effect as immunomodulators and which one is the best choice for RA SAH
      patients. Methods: Peripheral Blood Mononuclear Cells (PBMCs) from 16 RA patients
      were purified and stimulated or not stimulated with anti-CD3 and anti-CD28 mAB
      and were treated with Enalapril, Losartan and Valsartan at 100MUM. Patients were
      evaluated for clinical and laboratory variables including measures of disease
      activity by Clinical Disease Activity Index (CDAI) and Disease Activity Score
      (DAS28). Cytokines were quantified by ELISA sandwich. Results: Losartan was able
      to reduce levels of IFN-gamma (p = 0.0181), IL-6 (p = 0.0056), IL-17F (0.0046)
      and IL-22 (p = 0.0234) in RA patients. In addition, patients in remission and
      mild score (DAS28<3.2 and CDAI<10) had a better response to treatment. On the
      other hand, patients in moderate and severe activity had poor response to
      Losartan in cytokine inhibition. Conclusion: PBMCs from RA patients are
      responsive in inhibiting proinflammatory cytokines using Losartan better than
      Enalapril and Valsartan and it could be a better antihypertensive choice for
      patients with RA and systemic arterial hypertension treatment.

PMID- 30288191
TI  - Pelvic Tilt Angle Differences Between Symptom-Free Young Subjects and Elderly
      Patients Scheduled for THA: The Rationale for Tilt-Adjusted Acetabular Cup
      Implantation.
AB  - Background: The question whether Pelvic Tilt (PT) angles measured in the supine
      position are adequate for the alignment of the acetabular cup without an
      adjustment for anatomical differences between patients is of clinical importance.
      The aim of this work was to test for factors that can significantly affect PT
      angles. Methods: In the present retrospective cohort comparison, the PT angles of
      12 Symptom-Free Young Subjects (SFYS) and 45 patients scheduled for Total Hip
      Arthroplasty (THA) were compared. The data was collected during two studies with
      the use of a novel smartphone-based navigated ultrasound measurement system.
      Multi-factorial analysis of variance was run to determine which factors
      significantly affect PT. Results: Body position (F= 126.65; P< 0.001) and group
      (SFYS vs. THA patients) (F= 17.52; P< 0.001) had significant main effects on PT.
      There was also a significant interaction between body position and group (F=
      25.59; P< 0.001). The mean PT increased by 8.1 degrees  from an interiorly to a
      neutral tilted position (P< 0.001) and 21.4 degrees  from a neutral to a
      posteriorly tilted position (P< 0.001) with the transition from the supine into
      the upright position for the SFYS and THA patients, respectively. Conclusion: In
      both groups, PT changed significantly with a transition from the supine to the
      upright position. A position-dependent mean PT increase in the patient group
      showed that acetabular cup alignment based on PT in the supine position is not
      reliable without taking into consideration the inclination of the pelvis in
      standing position. This may lead to instability and dislocations.

PMID- 30288193
TI  - Emerging and Zoonotic Virus Challenges of Developing Nations.

PMID- 30288192
TI  - Effects of Arthroscopic Coracohumeral Ligament Release on Range of Motion for
      Patients with Frozen Shoulder.
AB  - Background: A thickened coracohumeral ligament is a highly specific manifestation
      of, and primary restraint against external rotation in frozen shoulders.
      Objective: The purpose of this study was to evaluate the effects of complete
      arthroscopic coracohumeral ligament release on range of motion in frozen
      shoulder. Methods: Fifty-two consecutive shoulders in 52 patients were treated
      between April 2015 and June 2016. To evaluate solely glenohumeral range of
      motion, the scapula was fixed by an examiner with one hand (without palpating
      scapular motion), and range of motion was measured using a goniometer. For the
      first step, arthroscopic pancapsular release was performed in a beach-chair
      position with (Group 1) or without (Group 2) complete coracohumeral ligament
      release. For the final step, the remaining coracohumeral ligaments in Group 2
      were released and the ranges of motion were compared to those in Group 1.
      Results: The average age of the patients was significantly higher in Group 1, but
      there were no significant differences between the two groups with respect to sex,
      affected side, preoperative range of motion, or American Shoulder and Elbow
      Society Score. Abduction, external rotation at adduction, and external and
      internal rotations at 90 degrees  of flexion in Group 1 were significantly
      greater than those in Group 2. After the additional release of the remaining
      coracohumeral ligaments in Group 2, all ranges of motion were significantly
      recovered and there was no significant difference between the groups. Conclusion:
      Complete coracohumeral ligament release is a recommended intraoperative procedure
      for regaining full range of motion in frozen shoulders.

PMID- 30288194
TI  - Chandipura Viral Encephalitis: A Brief Review.
AB  - Introduction: In recent years, the Chandipura virus (CHPV) has emerged as an
      encephalitic pathogen and found associated with a number of outbreaks in
      different parts of India. Children under 15 years of age are most susceptible to
      natural infection. CHPV is emerging as a significant encephalitis, causing virus
      in the Indian subcontinent. Severe outbreaks caused by the virus have been
      reported from several parts of India. Expalanation: In the recent past, the
      noticeable association of CHPV with pediatric sporadic encephalitis cases as well
      as a number of outbreaks in Andhra Pradesh (2004, 2005, 2007 and 2008), Gujarat
      in (2005, 2009-12) and Vidarbha region of Maharashtra (2007, 2009-12) have been
      documented. Prevalence and seasonal activity of the virus in these regions are
      established by NIV through outbreak investigations, sero-survey and diagnosis of
      the referred clinical specimens. Recently CHPV has been isolated from pools of
      sand flies collected during outbreak investigations in Vidarbha region of
      Maharashtra. Since its discovery from India and above-mentioned activity of CHPV,
      it was suspected to be restricted only to India. Conclusion: However, CHPV has
      also been isolated from human cases during 1971-72 in Nigeria, and hedgehogs
      (Atelerix spiculus) during entomological surveillance in Senegal, Africa (1990
      96) and recently referred samples from Bhutan and Nepal and from wild toque
      macaques (Macaca sinica) at Polonnaruwa, Sri Lanka during 1993 suggest its
      circulation in many tropical countries. Based on the limited study on vector
      related report, it appears that sandflies may be the principle vector.

PMID- 30288196
TI  - The Quest for Materials-Based Hydrogels with Antimicrobial and Antiviral
      Potentialities.
AB  - In recent years, the Antimicrobial Resistance (AMR) or Multidrug Resistance (MDR)
      and viral infections have become serious health issues, globally. Finally, after
      decades of negligence, the AMR/MDR and viral infection issues have now captured a
      worldwide attention of the global leaders, public health community, legalization
      authorities, academia, research-based organizations, and medicinal sector of the
      modern world, alike. Aiming to resolve these issues, various methodological
      approaches have been exploited, in the past several years. Among them,
      biomaterials-based therapeutic hydrogels are of supreme interests for an enhanced
      and efficient delivery in the current biomedical sector. Depending on the
      regulatory authorities and practices, the antibiotics consumption was expedited
      than ever before driven by rising and increasing access, across the globe. Though
      the emergence of AMR/MDR in microorganisms and emergence/reemergence of viral
      infections are considered as a natural phenomenon, however, these concerning
      issues have been driven by those mentioned above faulty human behavior. In this
      context, many scientists, around the globe, are working at wider spectrum to
      resolve this problematic issue, efficiently. A proper understanding of biological
      mechanisms is essential to combat this global threat to the living beings. In
      this review, an effort has been made to highlight the potent features of
      materials based hydrogels possessing antimicrobial and antiviral potentialities.
      The information is also given on the potential research activities, and possible
      mechanisms of actions of hydrogels are discussed with a closeup look at the
      future recommendations.

PMID- 30288195
TI  - Adaptation of Newcastle Disease Virus (NDV) in Feral Birds and their Potential
      Role in Interspecies Transmission.
AB  - Introduction: Newcastle Disease (ND), caused by Avian avulavirus 1 (AAvV 1,
      avulaviruses), is a notifiable disease throughout the world due to the economic
      impact on trading restrictions and its embargoes placed in endemic regions. The
      feral birds including aquatic/migratory birds and other wild birds may act as
      natural reservoir hosts of ND Viruses (NDVs) and may play a remarkable role in
      the spread of the virus in environment. In addition, other 19 avulaviruses
      namely: AAvV 2 to 20, have been potentially recognized from feral avian species.
      Expalantion: Many previous studies have investigated the field prevailing NDVs to
      adapt a wide range of susceptible host. Still the available data is not enough to
      declare the potential role of feral birds in transmission of the virus to poultry
      and/or other avian birds. In view of the latest evidence related to incidences of
      AAvVs in susceptible avian species, it is increasingly important to understand
      the potential of viruses to transmit within the domestic poultry and other avian
      hosts. Genomic and phylogenomic analysis of several investigations has shown the
      same (RK/RQRR?F) motif cleavage site among NDV isolates with same genotypes from
      domestic poultry and other wild hosts. So, the insight of this, various semi
      captive/free-ranging wild avian species could play a vital role in the
      dissemination of the virus, which is an important consideration to control the
      disease outbreaks. Insufficient data on AAvV 1 transmission from wild birds to
      poultry and vice versa is the main constraint to understand about its molecular
      biology and genomic potential to cause infection in all susceptible hosts.
      Conclusion: The current review details the pertinent features of several
      historical and contemporary aspects of NDVs and the vital role of feral birds in
      its molecular epidemiology and ecology.

PMID- 30288198
TI  - Epidemiologic Status of Picobirnavirus in India, A Less Explored Viral Disease.
AB  - Since the unexpected discovery of picobirnaviruses (PBV) in 1988, they have been
      reported in many animals including mammals and birds, which comprises both
      terrestrial and marine species. Due to their divergent characteristics to other
      viral taxa they are classified into a new family Picobirnaviridae. Although their
      pathogenicity and role in causing diarrhea still remains a question since they
      have been discovered in symptomatic and asymptomatic cases both. Recent studies
      employing state-of-art molecular tools have described their presence in various
      clinical samples, like stool samples from different mammals and birds,
      respiratory tracts of pigs and humans, sewage water, different foods, etc.
      Furthermore, their epidemiological status from different parts of the world in
      different hosts has also increased. Due to their diverse host and irregular host
      pattern their role in causing diarrhea remains alien. The heterogeneity nature
      can be ascribed to segmented genome of PBV, which renders them prone to
      continuous reassortment. Studies have been hampered on PBVs due to their non
      adaptability to cell culture system. Here, we describe the molecular
      epidemiological data on PBVs in India and discusses the overall status of
      surveillance studies carried out till date in India.

PMID- 30288197
TI  - Zoonotic Viral Diseases of Equines and Their Impact on Human and Animal Health.
AB  - Introduction: Zoonotic diseases are the infectious diseases that can be
      transmitted to human beings and vice versa from animals either directly or
      indirectly. These diseases can be caused by a range of organisms including
      bacteria, parasites, viruses and fungi. Viral diseases are highly infectious and
      capable of causing pandemics as evidenced by outbreaks of diseases like Ebola,
      Middle East Respiratory Syndrome, West Nile, SARS-Corona, Nipah, Hendra, Avian
      influenza and Swine influenza. Expalantion: Many viruses affecting equines are
      also important human pathogens. Diseases like Eastern equine encephalitis (EEE),
      Western equine encephalitis (WEE), and Venezuelan-equine encephalitis (VEE) are
      highly infectious and can be disseminated as aerosols. A large number of horses
      and human cases of VEE with fatal encephalitis have continuously occurred in
      Venezuela and Colombia. Vesicular stomatitis (VS) is prevalent in horses in North
      America and has zoonotic potential causing encephalitis in children. Hendra virus
      (HeV) causes respiratory and neurological disease and death in man and horses.
      Since its first outbreak in 1994, 53 disease incidents have been reported in
      Australia. West Nile fever has spread to many newer territories across continents
      during recent years.It has been described in Africa, Europe, South Asia, Oceania
      and North America. Japanese encephalitis has expanded horizons from Asia to
      western Pacific region including the eastern Indonesian archipelago, Papua New
      Guinea and Australia. Rabies is rare in horses but still a public health concern
      being a fatal disease. Equine influenza is historically not known to affect
      humans but many scientists have mixed opinions. Equine viral diseases of zoonotic
      importance and their impact on animal and human health have been elaborated in
      this article. Conclusion: Equine viral diseases though restricted to certain
      geographical areas have huge impact on equine and human health. Diseases like
      West Nile fever, Hendra, VS, VEE, EEE, JE, Rabies have the potential for spread
      and ability to cause disease in human. Equine influenza is historically not known
      to affect humans but some experimental and observational evidence show that H3N8
      influenza virus has infected man. Despite our pursuit of understanding the
      complexity of the vector-host-pathogen mediating disease transmission, it is not
      possible to make generalized predictions concerning the degree of impact of
      disease emergence. A targeted, multidisciplinary effort is required to understand
      the risk factors for zoonosis and apply the interventions necessary to control
      it.

PMID- 30288199
TI  - Evidence of BVDV in Pigs from North Eastern Part of India- Genetic Profiling and
      Characterisation.
AB  - Introduction: The work has been attempted to detect and genetically characterise
      the nature of Bovine Viral Diarrhea Virus (BVDV) isolates from the porcine
      population of the north east. Methods and Material: The samples have been
      collected over a two year period and are from areas where there is a mixed and
      integrated rearing of livestock in close proximity. The isolates were identified,
      cloned and sequenced using BVD specific genomic primers for two important domains
      viz., E-2 and 5' UTR. Results: Porcine BVD Sequences were analysed
      phylogenetically. Divergence in 3 sequences is noted in the 5' UTR region that
      are forming a clear outlier group while E-2 sequences are coming close to BVDV
      group but forming a separate cluster.

PMID- 30288201
TI  - Impact of Emerging, Re-Emerging and Zoonotic Viral Infectious Diseases, in a
      Virologist's Perspective.

PMID- 30288200
TI  - Japanese Encephalitis: A Brief Review on Indian Perspectives.
AB  - Introduction: Japanese encephalitis (JE) is recently declared as a notifiable
      disease in India due to its expanding geographical distribution. The disease
      notification facilitates effective implementation of preventive measures and case
      management. Expalantion: JE is a vector-borne disease that can be prevented by
      vaccine administration. It is caused by Japanese encephalitis virus (JEV),
      belonging to family Flaviviridae. Amongst the known etiological viral
      encephalitis agents, it is one of the leading viral agents of acute encephalitis
      syndrome in many Asian countries where it is identified to cause substantial
      morbidity and mortality as well as disability. Globally, it is responsible for
      approximately 68,000 clinical cases every year. Conclusion: In the absence of
      antivirals, patients are given supportive treatment to relieve and stabilize.
      Amongst available control strategies; vector control is resource intensive while
      animal and human vaccination are the most effective tool against the disease.
      This review highlights recent progress focusing challenges with diagnosis and
      prophylactic interventions.

PMID- 30288202
TI  - Teleburn: Designing A Telemedicine Application to Improve Burn Treatment.
AB  - Background: Due to the increasing rate of the burn injuries and a limited number
      of specialized treatment centers, providing medical advice and medical care at
      the point of need is necessary. The aim of the present study was to design and
      implement a teleburn system to enhance the quality of care for the burn patients.
      Methods: This study was completed in 2016. In order to design the system,
      information needs assessment was conducted by using a questionnaire. The
      participants of this phase were five specialists, five general practitioners, and
      12 nurses. The setting of the study was the burn department of a public hospital
      and a burn center. The prototype of the system was designed based on the findings
      derived from the first phase, and the usability of the system was evaluated
      later. Results: The teleburn system was a web-based system with different
      sections for GPs/nurses and specialists. In total, 28 burn consultations were
      made successfully by using the system. The findings of the usability testing
      showed that most of the participants evaluated the system at a good level. The
      mean score for the specialists, general practitioners and nurses was 8.4+/-0.46,
      7.7+/-0.39, and 7.5+/-0.51, respectively. Conclusion: Although it was the first
      time in the country that the teleburn system was designed and introduced to the
      clinicians, they seemed to be satisfied with using the system. This system could
      help general practitioners and nurses to receive specialist's advice on a timely
      manner to improve the treatment of the burn patients. However, more research
      should be conducted to determine the effectiveness of using this technology in
      the real work environment.

PMID- 30288204
TI  - Bilingualism in the Early Years: What the Science Says.
AB  - Many children in North America and around the world grow up exposed to two
      languages from an early age. Parents of bilingual infants and toddlers have
      important questions about the costs and benefits of early bilingualism, and how
      to best support language acquisition in their children. Here, we separate common
      myths from scientific findings to answer six of parents' most common questions
      about early bilingual development.

PMID- 30288203
TI  - Endocannabinoids and related N-acylethanolamines: biological activities and
      metabolism.
AB  - The plant Cannabis sativa contains cannabinoids represented by Delta9
      tetrahydrocannabinol, which exert psychoactivity and immunomodulation through
      cannabinoid CB1 and CB2 receptors, respectively, in animal tissues.
      Arachidonoylethanolamide (also referred to as anandamide) and 2
      arachidonoylglycerol (2-AG) are well known as two major endogenous agonists of
      these receptors (termed "endocannabinoids") and show various cannabimimetic
      bioactivities. However, only 2-AG is a full agonist for CB1 and CB2 and mediates
      retrograde signals at the synapse, strongly suggesting that 2-AG is
      physiologically more important than anandamide. The metabolic pathways of these
      two endocannabinoids are completely different. 2-AG is mostly produced from
      inositol phospholipids via diacylglycerol by phospholipase C and diacylglycerol
      lipase and then degraded by monoacylglycerol lipase. On the other hand,
      anandamide is concomitantly produced with larger amounts of other N
      acylethanolamines via N-acyl-phosphatidylethanolamines (NAPEs). Although this
      pathway consists of calcium-dependent N-acyltransferase and NAPE-hydrolyzing
      phospholipase D, recent studies revealed the involvement of several new enzymes.
      Quantitatively major N-acylethanolamines include palmitoylethanolamide and
      oleoylethanolamide, which do not bind to cannabinoid receptors but exert anti
      inflammatory, analgesic, and anorexic effects through receptors such as
      peroxisome proliferator-activated receptor alpha. The biosynthesis of these non
      endocannabinoid N-acylethanolamines rather than anandamide may be the primary
      significance of this pathway. Here, we provide an overview of the biological
      activities and metabolisms of endocannabinoids (2-AG and anandamide) and non
      endocannabinoid N-acylethanolamines.

PMID- 30288207
TI  - Bilateral Hand Salvage With Simultaneous Pedicled Groin Flaps in an
      Immunocompromised Patient.

PMID- 30288205
TI  - Simulated climate change affects how biocrusts modulate water gains and
      desiccation dynamics after rainfall events.
AB  - Soil surface communities dominated by mosses, lichens and cyanobacteria
      (biocrusts) are common between vegetation patches in drylands worldwide, and are
      known to affect soil wetting and drying after rainfall events. While ongoing
      climate change is already warming and changing rainfall patterns of drylands in
      many regions, little is known on how these changes may affect the hydrological
      behaviour of biocrust-covered soils. We used eight years of continuous soil
      moisture and rainfall data from a climate change experiment in central Spain to
      explore how biocrusts modify soil water gains and losses after rainfall events
      under simulated changes in temperature (2.5 degrees C warming) and rainfall (33%
      reduction). Both rainfall amount and biocrust cover increased soil water gains
      after rainfall events, whereas experimental warming, rainfall intensity and
      initial soil moisture decreased them. Initial moisture, maximum temperature and
      biocrust cover, by means of enhancing potential evapotranspiration or by soil
      darkening, increased the drying rates and enhanced the exponential behaviour of
      the drying events. Meanwhile, warming reduced their exponential behaviour. The
      effects of climate change treatments on soil water gains and losses changed
      through time, with important differences between the first two years of the
      experiment and five years after its setup. These effects were mainly driven by
      the important reductions in biocrust cover and diversity observed under warming.
      Our results highlight the importance of long-term studies to understand soil
      moisture responses to ongoing climate change in drylands.

PMID- 30288206
TI  - Cyclodextrin-Promoted Fluorescence Detection of Aromatic Toxicants and Toxicant
      Metabolites in Commercial Milk Products.
AB  - The detection of polycyclic aromatic hydrocarbons (PAHs) and their metabolites in
      food and in agricultural sources is an important research objective due to the
      PAHs' known persistence, carcinogenicity, and toxicity. PAHs have been found in
      the milk of lactating cows, and in the leaves and stems of plants grown in PAH
      contaminated areas, thereby making their way into both cow milk and plant milk
      alternatives. Reported herein is the rapid, sensitive, and selective detection of
      10 PAHs and PAH metabolites in a variety of cow milks and plant milk alternatives
      using fluorescence energy transfer from the PAH to a high quantum yield
      fluorophore, combined with subsequent array-based statistical analyses of the
      fluorescence emission signals. This system operates with high sensitivity (low
      micromolar detection limits), selectivity (100% differentiation even between
      structurally similar analytes), and general applicability (for both unmodified
      lipophilic PAHs and highly polar oxidized PAH metabolites, as well as for
      different cow and plant milk samples). These promising results show significant
      potential to be translated into solid-state devices for the rapid, sensitive, and
      selective detection of PAHs and their metabolites in complex, commercial food
      products.

PMID- 30288208
TI  - COMBINING PHENOTYPIC AND RESTING-STATE FMRI DATA FOR AUTISM CLASSIFICATION WITH
      RECURRENT NEURAL NETWORKS.
AB  - Accurate identification of autism spectrum disorder (ASD) from resting-state
      functional magnetic resonance imaging (rsfMRI) is a challenging task due in large
      part to the heterogeneity of ASD. Recent work has shown better classification
      accuracy using a recurrent neural network with rsfMRI time-series as inputs.
      However, phenotypic features, which are often available and likely carry
      predictive information, are excluded from the model, and combining such data with
      rsfMRI into the recurrent neural network is not a straightforward task. In this
      paper, we present several methodologies for incorporating phenotypic data with
      rsfMRI into a single deep learning framework for classifying ASD. We test the
      proposed architectures using a cross-validation framework on the large,
      heterogeneous first cohort from the Autism Brain Imaging Data Exchange. Our best
      model achieved an accuracy of 70.1%, outperforming prior work.

PMID- 30288209
TI  - Correction: Development of highly active anti-Pneumocystis bisbenzamidines:
      insight into the influence of selected substituents on the in vitro activity.
AB  - [This corrects the article DOI: 10.1039/C7MD00445A.].

PMID- 30288210
TI  - Correction: Recent updates in the discovery and development of novel antimalarial
      drug candidates.
AB  - [This corrects the article DOI: 10.1039/C7MD00637C.].

PMID- 30288211
TI  - Correction: Novel valdecoxib derivatives by ruthenium(ii)-promoted 1,3-dipolar
      cycloaddition of nitrile oxides with alkynes - synthesis and COX-2 inhibition
      activity.
AB  - [This corrects the article DOI: 10.1039/C7MD00575J.].

PMID- 30288212
TI  - Correction: Synthesis and evaluation of nuciferine and roemerine enantiomers as 5
      HT2 and alpha1 receptor antagonists.
AB  - [This corrects the article DOI: 10.1039/C7MD00629B.].

PMID- 30288213
TI  - Correction: The critical role of novel benzophenone analogs on tumor growth
      inhibition targeting angiogenesis and apoptosis.
AB  - [This corrects the article DOI: 10.1039/C7MD00593H.].

PMID- 30288214
TI  - Correction: Conformationally restricted benzothienoazepine respiratory syncytial
      virus inhibitors: their synthesis, structural analysis and biological activities.
AB  - [This corrects the article DOI: 10.1039/C8MD00033F.].

PMID- 30288215
TI  - How big should your screening collection be?
AB  - We're going to need a bigger compound deck....

PMID- 30288216
TI  - Making figures: are you taking the best approach to maximize visibility?
AB  - You might have heard the expression "a figure is worth a thousand words". But,
      how important really is it to make nice, complete, and clear figures? Actually...
      extremely important! Taking the extra time and effort to optimize the quality and
      visibility of your figures is totally worth it. Figures can most rapidly catch
      the attention of readers and influence their decision to read or not read your
      manuscript. This opinion article provides insight into ways to maximize the
      visibility and impact of your figures! We hope you will find value in the tips
      provided and can't wait to see all your beautiful figures.

PMID- 30288218
TI  - Link between a high k on for drug binding and a fast clinical action: to be or
      not to be?
AB  - Review articles on binding kinetics essentially focus on drugs that dissociate
      slowly from their target since this is required for the successful treatment of
      many pathophysiological conditions. Recently, the therapeutic benefit of a high k
      on (i.e. the second order association rate constant) has also been linked to fast
      association and to a fast clinical action. Other studies, however, called this
      assertion into question since additional factors, like the dosing paradigm and
      the binding mechanism, are important as well. The still ongoing reticence about
      integrating binding kinetics in lead optimization programs motivated us to
      critically review the link between the drug's kinetic rate constants and their in
      vitro and in vivo target occupancy profile, with special focus on k on. The
      presented simulations tally with a positive link between a drug's
      effective/observed association rate (which is quite easy to determine in vitro)
      and the swiftness of its clinical action. On the other hand, the simulations show
      that the k on-concept should not be confounded with the effective association
      process since increasing this parameter only enhances the drug's in vitro and in
      vivo association under certain conditions: the binding mechanism should be
      suitable, rebinding (and thus the factors within the target's micro-environment
      that favour this mechanism) should not be too prominent and the dosage should not
      be kept in par with the drug's affinity. Otherwise, increasing k on could be
      ineffective or even be counter-productive.

PMID- 30288217
TI  - Transfection by cationic gemini lipids and surfactants.
AB  - Diseases that are linked to defective genes or mutations can in principle be
      cured by gene therapy, in which damaged or absent genes are either repaired or
      replaced by new DNA in the nucleus of the cell. Related to this, disorders
      associated with elevated protein expression levels can be treated by RNA
      interference via the delivery of siRNA to the cytoplasm of cells. Polynucleotides
      can be brought into cells by viruses, but this is not without risk for the
      patient. Alternatively, DNA and RNA can be delivered by transfection, i.e. by non
      viral vector systems such as cationic surfactants, which are also referred to as
      cationic lipids. In this review, recent progress on cationic lipids as
      transfection vectors will be discussed, with special emphasis on geminis,
      surfactants with 2 head groups and 2 tails connected by a spacer.

PMID- 30288221
TI  - Development of subnanomolar-affinity serotonin 5-HT4 receptor ligands based on
      quinoline structures.
AB  - Two small series of quinoline derivatives were designed starting from previously
      published quinoline derivatives 7a and b in order to obtain information about
      their interaction with the 5-HT4R binding site. Initially, the structure of 7a
      and b was modified by replacing their basic moiety with that of partial agonist 4
      (ML10302) or with that of reference ligand 6 (RS-67-333). Then, the aromatic
      moieties of 4-quinolinecarboxylates 7a, d-f, and h-k or 4-quinolinecarboxamides
      7b, c, and g were modified into those of 2-quinolinecarboxamides 9a-e. Very
      interestingly, this structure-affinity relationship study led to the discovery of
      7h-j as novel 5-HT4R ligands showing K i values in the subnanomolar range. The
      structures of all these compounds contain the N-butyl-4-piperidinylmethyl
      substituent, which appear to behave as an optimized basic moiety in the
      interaction of these 4-quinolinecarboxylates with the 5-HT4R binding site.
      However, this basic moiety was ineffective in providing 5-HT4R affinity in the
      corresponding 4-quinolinecarboxamide 7g, but it did in 2-quinolinecarboxamide
      ligands 9c-e. Thus, a subtle interrelationship of several structural parameters
      appeared to play a major role in the interaction of the ligands with the 5-HT4R
      binding site. They include the kind of basic moiety, the position of the carbonyl
      linking group with respect to the aromatic moiety and its orientation, which
      could be affected by the presence of the intramolecular H-bond as in compounds 9c
      e.

PMID- 30288220
TI  - Design, synthesis, and evaluation of bitopic arylpiperazine-phthalimides as
      selective dopamine D3 receptor agonists.
AB  - The dopamine D3 receptor (D3R) is a proven therapeutic target for the treatment
      of neurological and neuropsychiatric disorders. In particular, D3R-selective
      ligands that can eliminate side effects associated with dopamine D2 receptor
      (D2R) therapeutics have been validated. However, the high homology in signaling
      pathways and the sequence similarity between D2R and D3R have rendered the
      development of D3R-selective ligands challenging. Herein, we designed and
      synthesized a series of piperazine-phthalimide bitopic ligands based on a
      fragment-based and molecular docking inspired design. Compound 9i was identified
      as the most selective D3R ligand among these bitopic ligands. Its selectivity was
      improved compared to reference compounds 1 and 2 by 9- and 2-fold, respectively,
      and it was 21-fold more potent than compound 2. Molecular docking demonstrated
      that the orientation of Leu2.64 and Phe7.39 and the packing at the junction of
      helices may affect the specificity for D3R over D2R. Functional evaluation
      revealed that D3R-selective ligand 9i displayed a subpicomolar agonist activity
      at D3R with a 199-fold increase in potency compared to quinpirole. These results
      may be useful for the fragment-based design of bitopic compounds as selective D3R
      ligands.

PMID- 30288222
TI  - Design, synthesis, and evaluation of 4,5,6,7-tetrahydrobenzo[d]thiazole-based
      novel dual kinase inhibitors of CK2 and GSK3beta.
AB  - Casein kinase 2 (CK2) and glycogen synthase kinase-3beta (GSK3beta) are
      responsible for the phosphorylation of a tumor suppressor protein (PTEN) in a
      cooperative manner which causes its deactivation. Thus, it is essential to
      inhibit both kinases simultaneously to prevent PTEN deactivation more
      efficiently. In this study, we have designed a novel lead from Hit15 which was
      identified in silico as a dual kinase inhibitor against CK2 and GSK3beta through
      our previous study. The dataset of structural analogs of the lead was designed
      and confirmed by pharmacophore mapping and molecular docking. The screened
      analogs were considered further and a series of "tetrahydrobenzo[d]thiazoles"
      were synthesized. Compound 1g has shown highest dual kinase inhibitory activity
      at a concentration of 1.9 MUM against CK2 and 0.67 MUM against GSK3beta. Our
      results suggest that the presence of a carboxyl group at the meta position of the
      phenyl ring plays a vital role in dual kinase inhibition.

PMID- 30288219
TI  - beta-lactam/beta-lactamase inhibitor combinations: an update.
AB  - Antibiotic resistance caused by beta-lactamase production continues to present a
      growing challenge to the efficacy of beta-lactams and their role as the most
      important class of clinically used antibiotics. In response to this threat
      however, only a handful of beta-lactamase inhibitors have been introduced to the
      market over the past thirty years. The first-generation beta-lactamase inhibitors
      (clavulanic acid, sulbactam and tazobactam) are all beta-lactam derivatives and
      work primarily by inactivating class A and some class C serine beta-lactamases.
      The newer generations of beta-lactamase inhibitors including avibactam and
      vaborbactam are based on non-beta-lactam structures and their spectrum of
      inhibition is extended to KPC as an important class A carbapenemase. Despite
      these advances several class D and virtually all important class B beta
      lactamases are resistant to existing inhibitors. The present review provides an
      overview of recent FDA-approved beta-lactam/beta-lactamase inhibitor combinations
      as well as an update on research efforts aimed at the discovery and development
      of novel beta-lactamase inhibitors.

PMID- 30288223
TI  - Phenothiazine antioxidants increase mitochondrial biogenesis and frataxin levels
      in Friedreich's ataxia cells.
AB  - Friedreich's ataxia (FRDA) is a progressive neurodegenerative disease that is
      linked to transcriptional repression of the nuclear FXN gene encoding the
      essential mitochondrial protein frataxin (FXN). Compounds that increase frataxin
      levels may enable effective therapeutic intervention for blunting disease
      progression. Recently, we showed that lipophilic methylene violet (MV) and
      methylene blue (MB) analogues both conferred benefit to cultured FRDA cells in
      several regards, including ROS suppression, maintenance of mitochondrial membrane
      potential and increased ATP production. Some of the MB analogues were also shown
      to promote increased frataxin levels and mitochondrial biogenesis. Presently, we
      report that two of the MV analogues studied previously (1 and 2) also increased
      frataxin levels and mitochondrial biogenesis significantly. Because the
      substitution pattern in the two series of compounds was not the same, we also
      prepared new MV derivatives having the same substitution pattern as the original
      MB derivatives studied to enable a more direct comparison. Two of the new MV
      compounds, 4b and 6b, exhibited enhanced antioxidant capability, increased
      frataxin levels and mitochondrial biogenesis, and improved aconitase activity.
      These encouraging findings demonstrated that the MV analogues had better overall
      activity with less cytotoxicity.

PMID- 30288224
TI  - Glycyrrhizic acid from licorice down-regulates inflammatory responses via
      blocking MAPK and PI3K/Akt-dependent NF-kappaB signalling pathways in TPA-induced
      skin inflammation.
AB  - Glycyrrhizinic acid (GA), a principal component derived from licorice which is
      used extensively as a natural sweetener and traditional folk herbal medicine, is
      attracting considerable attention because of its broad range of bioactivities.
      However, the anti-inflammatory mechanism of GA on 12-O-tetradecanoylphorbol-13
      acetate (TPA)-mediated skin inflammation has not been elucidated. Herein, we
      investigated the anti-inflammatory activity of GA by using a TPA-induced mouse
      ear model. It was indicated that GA, applied topically onto mouse ears,
      effectively inhibited the TPA-mediated expressions of inducible nitric oxide
      synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner,
      respectively. Mechanistic investigations demonstrated that GA down-regulated the
      expressions of IkappaBalpha and p65 and blocked the phosphorylation of
      IkappaBalpha and p65 in TPA-induced mouse skin. Moreover, GA significantly
      inhibited the TPA-mediated activation of extracellular signal-regulated kinase
      (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3
      kinase (PI3K)/Akt, which are upstream of nuclear factor-kB (NF-kappaB). Taken
      together, these results indicated that GA, being of natural origin, may be a
      potential agent for preventing inflammatory diseases.

PMID- 30288225
TI  - Synthesis and biological evaluation of novel 5-chloro-N-(4-sulfamoylbenzyl)
      salicylamide derivatives as tubulin polymerization inhibitors.
AB  - A novel series of sulfonamide derivatives, coupled with a salicylamide scaffold,
      was designed and synthesized. The structures of the synthesized compounds were
      established using 1H NMR, 13C NMR and high-resolution mass spectroscopy. The
      synthesized compounds were tested in vitro against five types of human cell
      lines. Two were breast adenocarcinoma, including the hormone-dependent MCF-7 and
      the hormone-independent MDA-MB-231. The others were the colorectal adenocarcinoma
      Caco-2, the carcinoma HCT-116 and the immortalized retinal-pigmented epithelium,
      hTERT-RPE1. Nine sulfonamides were able to inhibit the growth of the four tested
      cancer cells. Compound 33 was the most active against the selected colon cancer
      (Caco-2 and HCT-116) subtypes, while compound 24 showed the best efficacy against
      the examined breast cancer (MCF-7 and MDA-MB-231) cells. The selectivity index
      introduced compounds 24 and 33 as having the best selectivity among the breast
      and colon subtypes, respectively. In vitro tubulin polymerization experiments and
      flow cytometric assays showed that compounds 24 and 33 led to cell cycle arrest
      at the G2/M phase in a dose-dependent manner by effectively inhibiting tubulin
      polymerization. Furthermore, the results of the molecular docking studies
      indicate that this class of compounds can bind to the colchicine-binding site of
      tubulin.

PMID- 30288226
TI  - Novel organophosphorus aminopyrimidines as unique structural DNA-targeting
      membrane active inhibitors towards drug-resistant methicillin-resistant
      Staphylococcus aureus.
AB  - A series of novel unique structural organophosphorus aminopyrimidines were
      developed as potential DNA-targeting membrane active inhibitors through an
      efficient one-pot procedure from aldehydes, phosphonate and aminopyrimidine. The
      biological assay revealed that some of the prepared compounds displayed
      antibacterial activities. In particular, imidazole derivative 2c exhibited more
      potent inhibitory activity against MRSA with an MIC value of 4 MUg mL-1 in
      comparison with the clinical drugs chloromycin and norfloxacin. Experiments
      revealed that the active molecule 2c had the ability to rapidly kill the tested
      strains without obviously triggering the development of bacterial resistance,
      showed low toxicity to L929 cells and could disturb the cell membrane. The
      molecular docking study discovered that compound 2c could bind with DNA gyrase
      via hydrogen bonds and other weak interactions. Further exploration disclosed
      that the active molecule 2c could also effectively intercalate into MRSA DNA and
      form a steady 2c-DNA supramolecular complex, which might further block DNA
      replication to exert powerful antibacterial effects.

PMID- 30288227
TI  - Lipophilicity prediction of peptides and peptide derivatives by consensus machine
      learning.
AB  - Lipophilicity prediction is routinely applied to small molecules and presents a
      working alternative to experimental log P or log D determination. For compounds
      outside the domain of classical medicinal chemistry these predictions lack
      accuracy, advocating the development of bespoke in silico approaches. Peptides
      and their derivatives and mimetics fill the structural gap between small
      synthetic drugs and genetically engineered macromolecules. Here, we present a
      data-driven machine learning method for peptide log D 7.4 prediction. A model for
      estimating the lipophilicity of short linear peptides consisting of natural amino
      acids was developed. In a prospective test, we obtained accurate predictions for
      a set of newly synthesized linear tri- to hexapeptides. Further model development
      focused on more complex peptide mimetics from the AstraZeneca compound
      collection. The results obtained demonstrate the applicability of the new
      prediction model to peptides and peptide derivatives in a log D 7.4 range of
      approximately -3 to 5, with superior accuracy to established lipophilicity models
      for small molecules.

PMID- 30288228
TI  - 2-Aminobenzimidazoles as antibiofilm agents against Salmonella enterica serovar
      Typhimurium.
AB  - Serovars within the species Salmonella enterica are some of the most common food
      and water-borne pathogens worldwide. Some S. enterica serovars have shown a
      remarkable ability to persist both inside and outside the human body. Salmonella
      enterica serovar Typhi can cause chronic, asymptomatic infection of the human
      gallbladder. This organism's ability to survive inside the gallbladder centers
      around its ability to form biofilms on gallstone surfaces. Currently, chronic
      carriage of S. Typhi is treated by invasive methods, which are not well suited to
      areas where Salmonella carriage is prevalent. Herein, we report 2
      aminobenzimidazoles that inhibit S. enterica serovar Typhimurium (a surrogate for
      S. Typhi) biofilm formation in low micromolar concentrations. Modifications to
      the head, tail, and linker regions of the original hit compound elucidated new,
      more effective analogues that inhibit S. Typhimurium biofilm formation while
      being non-toxic to planktonic bacterial growth.

PMID- 30288230
TI  - Correction: A benzylic linker promotes methyltransferase catalyzed norbornene
      transfer for rapid bioorthogonal tetrazine ligation.
AB  - [This corrects the article DOI: 10.1039/C7SC03631K.].

PMID- 30288229
TI  - Synthesis of novel perillyl-dihydropyrimidinone hybrids designed for
      antiproliferative activity.
AB  - A series of fifteen novel dihydropyrimidinone hybrid compounds were synthesized
      in good yields via a multicomponent reaction combined with the Huisgen reaction.
      The antiproliferative activity was investigated against nine tumor cell lines,
      and four hybrid compounds (TGI < 10 MUM) showed promising antiproliferative
      activity against the tumor cell lines OVCAR-3 (ovarian), UACC-62 (melanoma) and
      U251 (glioma). Several hybrid compounds assayed have high TGI values (TGI 147.92
      507.82) for the human keratinocyte cell line (HaCat), which reveals selectivity
      to cancer cells.

PMID- 30288231
TI  - Enantioselective aza-Friedel-Crafts reaction of furan with alpha-ketimino esters
      induced by a conjugated double hydrogen bond network of chiral bis(phosphoric
      acid) catalysts.
AB  - Chiral C 2- and C 1-symmetric BINOL-derived bis(phosphoric acid) catalysts, which
      have OP([double bond, length as m-dash]O)(OH)2/OP([double bond, length as m
      dash]O)(OH)(OR) moieties at the 2,2'-positions, were developed and used for the
      enantioselective aza-Friedel-Crafts reaction of 2-methoxyfuran with alpha
      ketimino esters for the first time. The intramolecular conjugated double hydrogen
      bond network is a key to increasing the Bronsted acidity and preventing
      deactivation of the catalysts. Highly functionalized alpha-amino acid derivatives
      with a chiral quaternary carbon center could be transformed into versatile
      optically active N- and O-heterocycles and an alpha-aryl-substituted serine.

PMID- 30288232
TI  - N-Heterocyclic carbenes as chiral Bronsted base catalysts: a highly diastereo-
      and enantioselective 1,6-addition reaction.
AB  - Highly diastereo- and enantioselective 1,6-addition of 1,3-ketoamides to p
      quinone methides (p-QMs) using chiral NHCs as Bronsted base catalysts is
      developed. The reaction is based on the utilization of a 1,3-ketoamide having
      acidic N-H that forms a chiral ion-pair consisting of the enolate and the azolium
      ion. Different beta-ketoamides and functionalized p-QMs are applicable to the
      reaction. Synthetic application of the method is demonstrated via the preparation
      of highly enantioenriched beta and gamma-lactam derivatives.

PMID- 30288233
TI  - Antibody drug conjugates (ADCs) charged with HDAC inhibitor for targeted
      epigenetic modulation.
AB  - We describe here two novel antibody-drug conjugates loaded with the HDAC
      inhibitor ST7612AA1 (IC50 equal to 0.07 MUM on NCI-H460 cells), a thiol-based
      molecule with a moderate toxicity in vivo. Two payloads were prepared using
      cleavable and non-cleavable linkers. After anchoring to cetuximab through amide
      bond with lysines, the resulting HDAC inhibitor-antibody conjugates showed
      ability to recognize EGFR and efficient internalization in tumor cells. Both ADCs
      induced sensible increment of histones 3 and 4 and alpha-tubulin acetylation.
      Animal models of human solid tumors showed high anti-tumor efficacy of the
      conjugates without the toxicity generally observed with traditional ADCs
      delivering highly potent cytotoxic drugs. These compounds, the first ADCs charged
      with not highly cytotoxic warheads, are potentially suitable for epigenetic
      modulation, extending the ADC strategy to the targeted delivery of HDAC
      inhibitors with many possible therapeutic applications beyond cancer.

PMID- 30288234
TI  - OH formation and H2 adsorption at the liquid water-Pt(111) interface.
AB  - The liquid water-Pt(111) interface is studied with constant temperature ab initio
      molecular dynamics to explore the importance of liquid water dynamics of
      catalytic reactions such as the oxygen reduction reaction in PEM fuel cells. The
      structure and energetics of hydroxyls formed at the liquid water-Pt(111)
      interface are found to be significantly different from those of the hydroxyl
      formed on a bare Pt(111) surface and the hydroxyl formed on a Pt(111) surface
      with a static water layer. We identify 1/12 ML *OH, 5/12 ML *OH and 2/3 ML *OH as
      particularly stable hydroxyl coverages in highly dynamic liquid water
      environments, which - contrary to static water-hydroxyl models - contain adjacent
      uncovered Pt sites. Atomic surface oxygen is found to be unstable in the presence
      of liquid water, in contrast to static atomic level simulations. These results
      give an improved understanding of hydroxide and surface oxide formation from
      Pt(111) cyclic voltammetry and allow us to draw detailed connections between the
      electrostatic potential and the interface structure. The study of hydrogen
      adsorption at the liquid water-Pt(111) interface finds competitive adsorption
      between the adsorbed hydrogen atoms and water molecules. This does not adhere
      with experimental observations, and this indicates that the Pt(111) surface has
      to be negatively charged for a correct description of the liquid water-Pt(111)
      interface at potentials where hydrogen adsorption occurs.

PMID- 30288235
TI  - [P4H]+[Al(OTeF5)4]-: protonation of white phosphorus with the Bronsted superacid
      H[Al(OTeF5)4](solv).
AB  - A sustainable transformation of white phosphorus (P4) into chemicals of higher
      value is one of the key aspects in modern phosphorus research. Even though the
      chemistry of P4 has been investigated for many decades, its chemical reactivity
      towards the simplest electrophile, the proton, is still virtually unknown. Based
      on quantum-chemical predictions, we report for the first time the successful
      protonation of P4 by the Bronsted acid H[Al(OTeF5)4](solv). Our spectroscopic
      results are in agreement with acid-mediated activation of P4 under protonation of
      an edge of the P4-tetrahedron and formation of a three-center two-electron P-H-P
      bond. These investigations are of fundamental interest as they permit the
      activation of P4 with the simplest electrophile as a new prototype reaction for
      this molecule.

PMID- 30288236
TI  - A fluorescent methylation-switchable probe for highly sensitive analysis of FTO N
      6-methyladenosine demethylase activity in cells.
AB  - N 6-Methyladenosine (m6A) is one of the most abundant epigenetic modifications on
      mRNA. It is dynamically regulated by the m6A demethylases FTO and ALKBH5, which
      are currently attracting intense medical interest because of their strong
      association with several human diseases. Despite their clinical significance, the
      molecular mechanisms of m6A demethylases remain unclear, hence there is
      tremendous interest in developing analytical tools to facilitate their functional
      studies, with a longer term view of validating their therapeutic potentials. To
      date, no method exists which permits the analysis of m6A-demethylase activity in
      cells. To overcome this challenge, herein, we describe the first example of a
      fluorescent m6A-switchable oligonucleotide probe, which enables the direct
      detection of FTO demethylase activity both in vitro and in living cells. The m6A
      probe provides a simple, yet powerful visual tool for highly sensitive detection
      of demethylase activity. Through the use of m6A-probe, we were able to achieve
      real-time imaging and single-cell flow cytometry analyses of FTO activity in
      HepG2 cells. We also successfully applied the probe to monitor dynamic changes in
      FTO activity and m6A methylation levels during 3T3-L1 pre-adipocyte
      differentiation. The strategy outlined here is highly versatile and may, in
      principle, be adapted to the study of a range of RNA demethylases and, more
      widely, other RNA modifying enzymes. To the best of our knowledge, the present
      study represents not only the first assay for monitoring FTO activity in living
      cells, but also a new strategy for sensing m6A methylation dynamics.

PMID- 30288237
TI  - Conformational selectivity and high-affinity binding in the complexation of N
      phenyl amides in water by a phenyl extended calix[4]pyrrole.
AB  - We describe the synthesis of a tetrapyridinium phenyl extended calix[4]pyrrole
      that is soluble in neutral water solution at mM concentrations. We show that, in
      pure water, the synthesized calix[4]pyrrole receptor selectively binds the cis
      (E) conformers of secondary N-phenyl-amides and tertiary N-methyl-N-phenyl
      formamide with binding affinities larger than 103 M-1. The conformational
      selectivity is remarkable owing to the energetic preference of amides to adopt
      the trans-(Z) conformation in solution. In this respect, we used two binding
      models for the mathematical analyses of the titration data and calculated
      apparent and intrinsic binding constants. The combined action of hydrogen bonding
      and the hydrophobic effect that operates in the binding of the amides in water is
      responsible for the large affinities displayed by the receptor.

PMID- 30288238
TI  - A mild light-induced cleavage of the S-O bond of aryl sulfonate esters enables
      efficient sulfonylation of vinylarenes.
AB  - A new mode of S-O bond activation has been discovered, which constitutes novel
      reactivity of easily available and bench-stable arylsulfonate phenol esters. This
      protocol enables access to putative sulfonyl radical intermediates, which enable
      straightforward access to valuable vinyl sulfones.

PMID- 30288239
TI  - Tetrazine-mediated bioorthogonal prodrug-prodrug activation.
AB  - The selective and biocompatible activation of prodrugs within complex biological
      systems remains a key challenge in medical chemistry and chemical biology. Herein
      we report, for the first time, a dual prodrug activation strategy that fully
      satisfies the principle of bioorthogonality by the symbiotic formation of two
      active drugs. This dual and traceless prodrug activation strategy takes advantage
      of the INVDA chemistry of tetrazines (here a prodrug), generating a pyridazine
      based miR21 inhibitor and the anti-cancer drug camptothecin and offers a new
      concept in prodrug activation.

PMID- 30288240
TI  - An "all-in-one" antitumor and anti-recurrence/metastasis nanomedicine with multi
      drug co-loading and burst drug release for multi-modality therapy.
AB  - Drug-loading often suffers from tedious procedures, limited loading efficiency,
      slow release, and therefore a low curative effect. Cancer easily recurs and
      metastasizes even after a solid tumor is removed. Herein, we report a simple
      strategy with multi-drug co-loading and burst drug release for a high curative
      effect and anti-recurrence/metastasis. CuS nanoparticles, protoporphyrin IX, and
      doxorubicin were added to the precursors of ZIF-8 with one-pot co-loading during
      the formation of ZIF-8 for chemo-, photothermal-, and photodynamic-therapy to
      eliminate solid tumors. Negative CpG, as a kind of immune adjuvant, was adsorbed
      on the positive surface of ZIF-8 to inhibit the recurrence and metastasis of
      tumors with its long-term immune response. Precision treatment with one-pot multi
      drug co-loading, controllable drug delivery, and multi-modality therapy may be
      anticipated by this versatile strategy.

PMID- 30288241
TI  - The hydrogen atom transfer reactivity of sulfinic acids.
AB  - Sulfinic acids (RSO2H) have a reputation for being difficult reagents due to
      their facile autoxidation. Nevertheless, they have recently been employed as key
      reagents in a variety of useful radical chain reactions. To account for this
      paradox and enable further development of radical reactions employing sulfinic
      acids, we have characterized the thermodynamics and kinetics of their H-atom
      transfer reactions for the first time. The O-H bond dissociation enthalpy (BDE)
      of sulfinic acids was determined by radical equilibration to be ~78 kcal mol-1;
      roughly halfway between the RS-H BDE in thiols (~87 kcal mol-1) and RSO-H BDE in
      sulfenic acids (~70 kcal mol-1). Regardless, RSH, RSOH and RSO2H have relatively
      similar inherent H-atom transfer reactivity to alkyl radicals (~106 M-1 s-1).
      Counter-intuitively, the trend in rate constants with more reactive alkoxyl
      radicals follows the reaction energetics: ~108 M-1 s-1 for RSO2H, midway between
      thiols (~107 M-1 s-1) and sulfenic acids (~109 M-1 s-1). Importantly, since
      sulfinic and sulfenic acids are very strong H-bond donors (alphaH2 ~ 0.63 and
      0.55, respectively), their reactivity is greatly attenuated in H-bond accepting
      solvents, whereas the reactivity of thiols is largely solvent-independent.
      Efforts to measure rate constants for the reactions of sulfinic acids with
      alkylperoxyl radicals were unsuccessful. Computations predict these reactions to
      be surprisingly slow; ~1000-times slower than for thiols and ~10 000 000-times
      slower than for sulfenic acids. On the other hand, the reaction of sulfinic acids
      with sulfonylperoxyl radicals - which propagate sulfinic acid autoxidation - is
      predicted to be almost diffusion-controlled. In fact, the rate-determining step
      in sulfinic acid autoxidation, and the reason they can be used for productive
      chemistry, is the relatively slow reaction of propagating sulfonyl radicals with
      O2 (~106 M-1 s-1).

PMID- 30288242
TI  - Photocatalytic Barbier reaction - visible-light induced allylation and
      benzylation of aldehydes and ketones.
AB  - We report a photocatalytic version of the Barbier type reaction using readily
      available allyl or benzyl bromides and aromatic aldehydes or ketones as starting
      materials to generate allylic or benzylic alcohols. The reaction proceeds at room
      temperature under visible light irradiation with the organic dye 3,7-di(4
      biphenyl)1-naphthalene-10-phenoxazine as a photocatalyst and DIPEA as sacrificial
      electron donor. The proposed cross-coupling mechanism of a ketyl- and an allyl or
      benzyl radical is supported by spectroscopic investigations and cyclic
      voltammetry measurements.

PMID- 30288243
TI  - Phosphorescent iridium(iii) complexes capable of imaging and distinguishing
      between exogenous and endogenous analytes in living cells.
AB  - Many luminescent probes have been developed for intracellular imaging and
      sensing. During cellular luminescence sensing, it is difficult to distinguish
      species generated inside cells from those internalized from extracellular
      environments since they are chemically the same and lead to the same luminescence
      response of the probes. Considering that endogenous species usually give more
      information about the physiological and pathological parameters of the cells
      while internalized species often reflect the extracellular environmental
      conditions, we herein reported a series of cyclometalated iridium(iii) complexes
      as phosphorescent probes that are partially retained in the cell membrane during
      their cellular uptake. The utilization of the probes for sensing and
      distinguishing between exogenous and endogenous analytes has been demonstrated
      using hypoxia and hypochlorite as two examples of target analytes. The endogenous
      analytes lead to the luminescence response of the intracellular probes while the
      exogenous analytes are reported by the probes retained in the cell membrane
      during their internalization.

PMID- 30288244
TI  - Probing cytoplasmic and nuclear microRNAs in single living cells via plasmonic
      affinity sandwich assay.
AB  - MicroRNAs (miRNAs) regulate the expression of mRNAs in cells. The determination
      of subcellular miRNAs in single living cells is essential for understanding the
      subcellular localizations and functions of miRNAs as well as the
      microheterogeneity of cells. However, current approaches fail either to keep the
      cells alive or maintain their original cellular composition or are unable to
      provide subcellular resolution. Herein, we presented a new approach, called
      plasmonic affinity sandwich assay (PASA), for rapid and ultrasensitive probing of
      trace cytoplasmic and nuclear miRNAs in single living cells. It combined
      efficient in vivo subcellular extraction with ultrasensitive plasmon-enhanced
      Raman scattering (PERS) detection. By virtue of a micromanipulator, target miRNAs
      in the cytoplasm and nucleus were first specifically extracted from single living
      cells by gold thinlayer-coated glass microprobes modified with a half
      complementary sequence to the target miRNA and then, they were labelled with
      silver nanotags modified with a Raman reporter and the other half complement.
      Sandwich-like complexes of extraction sequence-target miRNA-labelling sequence
      were formed on the extraction microprobe, which were subjected to PERS detection.
      The subcellular resolution of this approach was confirmed with miR-29b
      (predominantly localized in the nuclei) and miR-29a (mainly located in the
      cytoplasm), whereas the quantitative capability was verified with three
      cytoplasmic miRNAs including miR-21, miR-155 and miR-203. This approach obviated
      tedious steps such as subcellular fractionation and enzymatic amplification, and
      it required only 10 min. It could be a promising tool to provide insights into
      subcellular localizations, functions and microheterogeneity of miRNAs.

PMID- 30288245
TI  - Overcoming conservation in TALE-DNA interactions: a minimal repeat scaffold
      enables selective recognition of an oxidized 5-methylcytosine.
AB  - Transcription-activator-like effectors (TALEs) are repeat-based proteins
      featuring programmable DNA binding. The repulsion of TALE repeats by 5
      methylcytosine (5mC) and its oxidized forms makes TALEs potential probes for
      their programmable analysis. However, this potential has been limited by the
      inability to engineer repeats capable of actual, fully selective binding of an
      (oxidized) 5mC: the extremely conserved and simple nucleobase recognition mode of
      TALE repeats and their extensive involvement in inter-repeat interactions that
      stabilize the TALE fold represent major engineering hurdles. We evaluated
      libraries of alternative, strongly truncated repeat scaffolds and discovered a
      repeat that selectively recognizes 5-carboxylcytosine (5caC), enabling
      construction of the first programmable receptors for an oxidized 5mC. In
      computational studies, this unusual scaffold executes a dual function via a
      critical arginine that provides inter-repeat stabilization and selectively
      interacts with the 5caC carboxyl group via a salt-bridge. These findings argue
      for an unexpected adaptability of TALE repeats and provide a new impulse for the
      design of programmable probes for nucleobases beyond A, G, T and C.

PMID- 30288246
TI  - Carrier-doping as a tool to probe the electronic structure and multi-carrier
      recombination dynamics in heterostructured colloidal nanocrystals.
AB  - Heterostructured colloidal nanocrystals, such as core/shells and dot-in-rods,
      enable new spectral and dynamic properties otherwise unachievable with single
      component nanocrystals or quantum dots (QDs). For example, the electron and hole
      wavefunctions can be engineered such that they are either both confined in the
      same domain or (partially) separated over different domains in the
      heterostructures, which are the so-called type I or (quasi-) type II localization
      regimes, respectively. A critical factor dictating the carrier localization
      regime is the band alignment or electronic structure of the heterostructure,
      which, however, is difficult to measure and hence is often ambiguous. In this
      work, using CdSe@CdS dot-in-rods (DIRs) as a model system, we show that band edge
      carrier-doping is a simple-yet-powerful tool to probe the electronic structure of
      heterostructures. By doping an electron into the CdSe core and then observing
      whether the doped electron bleaches band edge absorption of only the core or
      those of both the core and shell, we can easily differentiate the type I and
      quasi-type II structures. A systematic study of DIRs with various dimensions
      shows that the extent of electron wavefunction delocalization can be tuned by the
      core sizes and rod diameters. Comparison with the electronic structure determined
      from transient absorption measurements also reveals the important role of
      electron-hole binding in affecting the delocalization of electron wavefunction.
      In addition to probing the electronic structure, the doped electron allows for
      studying multi-carrier recombination dynamics in these heterostructures which
      plays a vital role in their many optical and optoelectronic applications.
      Specifically, by comparing the band edge exciton recombination kinetics of the
      doped and neutral DIRs, we can extract the negative trion lifetime, which can be
      further used to derive the positive trion lifetime when combined with biexciton
      lifetime measurements. These lifetimes also depend sensitively on the core sizes
      and rod diameters of the DIRs.

PMID- 30288248
TI  - Performing DNA nanotechnology operations on a zebrafish.
AB  - Nanoscale engineering of surfaces is becoming an indispensable technique to
      modify membranes and, thus cellular behaviour. Here, such membrane engineering
      related was explored on the surface of a living animal using DNA nanotechnology.
      We demonstrate the immobilization of oligonucleotides functionalized with a
      membrane anchor on 2 day old zebrafish. The protruding single-stranded DNA on the
      skin of zebrafish served as a handle for complementary DNAs, which allowed the
      attachment of small molecule cargo, liposomes and dynamic relabeling by DNA
      hybridization protocols. Robust anchoring of the oligonucleotides was proven as
      DNA-based amplification processes were successfully performed on the outer
      membrane of the zebrafish enabling the multiplication of surface functionalities
      from a single DNA-anchoring unit and the dramatic improvement of fluorescent
      labeling of these animals. As zebrafish are becoming an alternative to animal
      models in drug development, toxicology and nanoparticles characterization, we
      believe the platform presented here allows amalgamation of DNA nanotechnology
      tools with live animals and this opens up yet unexplored avenues like efficient
      bio-barcoding as well as in vivo tracking.

PMID- 30288247
TI  - Tricarbocyanine N-triazoles: the scaffold-of-choice for long-term near-infrared
      imaging of immune cells in vivo.
AB  - Herein tricarbocyanine N-triazoles are first described as a rationally-designed
      near-infrared (NIR) structure overcoming the brightness and photostability
      limitations of tricarbocyanines for long-term in vivo imaging. The
      straightforward synthetic approach and the wide availability of alkynes makes
      this strategy a versatile methodology for the preparation of highly stable N
      substituted tricarbocyanines. Furthermore, we validated CIR38M as a non
      transferable marker to monitor the fate of therapeutic T cells non-invasively in
      vivo, showing enhanced performance over conventional NIR fluorophores (i.e. DiR,
      IR800CW and indocyanine green) as well as compatibility with human cells for
      translational studies. CIR38M is able to track over time smaller numbers of T
      cells than current NIR agents, and to visualise antigen-driven accumulation of
      immune cells at specific sites in vivo. This chemical technology will improve
      longitudinal imaging studies to assess the efficacy of cell-based immunotherapies
      in preclinical models and in human samples.

PMID- 30288249
TI  - Between single ion magnets and macromolecules: a polymer/transition metal-based
      semi-solid solution.
AB  - The creation of functional magnetic materials for application in high-density
      memory storage or in the new field of molecular spintronics is a matter of
      widespread interest among the material research community. Herein, we describe a
      new approach that combines the qualities of single ion magnets, displaying slow
      magnetic relaxations, and the merits of polymers, being easy to process and
      widely used to produce thin films. Basing the idea on cobalt(ii) ions and
      pyridine-based single ion magnets, a new macromolecular magnetic material was
      obtained - a polymeric matrix of poly(4-vinylpyridine) (P4VP) cross-linked by a
      cobalt(ii) salt bound within it, effectively forming a network of single ion
      magnets, with field-induced magnetic relaxations preserved in both bulk and thin
      film forms. The binding of cobalt is confirmed by a series of methods, like
      secondary ion mass spectroscopy or high-resolution X-ray photoelectron
      spectroscopy. The magnetic relaxation times, up to 5 * 10-6 s, are controllable
      simply by dilution, making this new material a semi-solid solution. By this
      approach, a new path is formed to connect molecular magnetism and polymer
      science, showing that the easy polymer processing can be used in forming self
      organizing functional magnetic thin films.

PMID- 30288250
TI  - Correction: Single quantum dot-based nanosensor for sensitive detection of 5
      methylcytosine at both CpG and non-CpG sites.
AB  - [This corrects the article DOI: 10.1039/C7SC04813K.].

PMID- 30288251
TI  - Erratum: Further Correction: Hypoxia inducible factor (HIF) as a model for
      studying inhibition of protein-protein interactions.
AB  - [This corrects the article DOI: 10.1039/C7SC00388A.].

PMID- 30288253
TI  - Phagocytosis influences the intracellular survival of Mycobacterium smegmatis via
      the endoplasmic reticulum stress response.
AB  - Background: Mycobacterium smegmatis, a rapidly growing non-tuberculosis
      mycobacterium, is a good model for studying the pathogenesis of tuberculosis
      because of its genetic similarity to Mycobacterium tuberculosis (Mtb).
      Macrophages remove mycobacteria during an infection. Macrophage apoptosis is a
      host defense mechanism against intracellular bacteria. We have reported that
      endoplasmic reticulum (ER) stress is an important host defense mechanism against
      Mtb infection. Results: In this study, we found that M. smegmatis induced strong
      ER stress. M. smegmatis-induced reactive oxygen species (ROS) play a critical
      role in the induction of ER stress-mediated apoptosis. Pretreatment with an ROS
      scavenger suppressed M. smegmatis-induced ER stress. Elimination of ROS decreased
      the ER stress response and significantly increased the intracellular survival of
      M. smegmatis. Interestingly, inhibition of phagocytosis significantly decreased
      ROS synthesis, ER stress response induction, and cytokine production.
      Conclusions: Phagocytosis of M. smegmatis induces ROS production, leading to
      production of proinflammatory cytokines. Phagocytosis-induced ROS is associated
      with the M. smegmatis-mediated ER stress response in macrophages. Therefore,
      phagocytosis plays a critical role in the induction of ER stress-mediated
      apoptosis during mycobacterial infection.

PMID- 30288254
TI  - Shape memory polymers with visible and near-infrared imaging modalities:
      Synthesis, characterization and in vitro analysis.
AB  - Shape memory polymers (SMPs) are promising for non-invasive medical devices and
      tissue scaffolds, but are limited by a lack of visibility under clinical imaging.
      Fluorescent dyes are an alternative to radiocontrast agents in medical
      applications, they can be utilized in chemical sensors and monitors and may be
      anti-microbial agents. Thus, a fluorescent SMP could be a highly valuable
      biomaterial system. Here, we show that four fluorescent dyes (phloxine B (PhB),
      eosin Y (Eos), indocyanine green(IcG), and calcein (Cal)) can be crosslinked into
      the polymer backbone to enhance material optical properties without alteration of
      shape memory and thermomechanical properties. Examinations of the emission
      wavelengths of the materials compared with the dye solutions showed a slight red
      shift in the peak emissions, indicative of crosslinking of the material.
      Quantitative analysis revealed that PhB enabled visibility through 1 cm of blood
      and through soft tissue. We also demonstrate the utility of these methods in
      combination with radio-opaque microparticle additives and the use of laser
      induced shape recovery to allow for rapid shape recovery below the glass
      transition temperature. The crosslinking of fluorescent dyes into the SMP enables
      tuning of physical properties and shape memory and independently of the
      fluorescence functionality. This fluorescent SMP biomaterial system allows for
      use of multiple imaging modalities with potential application in minimally
      invasive medical devices.

PMID- 30288252
TI  - Gene expression analysis of potential morphogen signalling modifying factors in
      Panarthropoda.
AB  - Background: Morphogen signalling represents a key mechanism of developmental
      processes during animal development. Previously, several evolutionary conserved
      morphogen signalling pathways have been identified, and their players such as the
      morphogen receptors, morphogen modulating factors (MMFs) and the morphogens
      themselves have been studied. MMFs are factors that regulate morphogen
      distribution and activity. The interactions of MMFs with different morphogen
      signalling pathways such as Wnt signalling, Hedgehog (Hh) signalling and
      Decapentaplegic (Dpp) signalling are complex because some of the MMFs have been
      shown to interact with more than one signalling pathway, and depending on genetic
      context, to have different, biphasic or even opposing function. This complicates
      the interpretation of expression data and functional data of MMFs and may be one
      reason why data on MMFs in other arthropods than Drosophila are scarce or totally
      lacking. Results: As a first step to a better understanding of the potential
      roles of MMFs in arthropod development, we investigate here the embryonic
      expression patterns of division abnormally delayed (dally), dally-like protein
      (dlp), shifted (shf) and secreted frizzled-related protein 125 (sFRP125) and
      sFRP34 in the beetle Tribolium castaneum, the spider Parasteatoda tepidariorum,
      the millipede Glomeris marginata and the onychophoran Euperipatoides
      kanangrensis. This pioneer study represents the first comprehensive comparative
      data set of these genes in panarthropods. Conclusions: Expression profiles reveal
      a high degree of diversity, suggesting that MMFs may represent highly evolvable
      nodes in otherwise conserved gene regulatory networks. Conserved aspects of MMF
      expression, however, appear to concern function in segmentation and limb
      development, two of the key topics of evolutionary developmental research.

PMID- 30288255
TI  - Phenotypic analysis of antibiotic resistance and genotypic study of the vacA,
      cagA, iceA, oipA and babA genotypes of the Helicobacter pylori strains isolated
      from raw milk.
AB  - Background: Foods with animal origins and particularly milk play a considerable
      role in transmission of Helicobacter pylori. The current study was performed to
      assess phenotypic characters of antibiotic resistance and genotyping pattern of
      vacA, cagA, iceA, oipA and babA2 alleles amongst the H. pylori strains isolated
      from raw milk. Methods: Six-hundred and thirty raw milk samples were collected
      and cultured on Wilkins Chalgren anaerobe media. Antibiotic resistance and
      genotyping patterns were studied using disk diffusion and PCR, respectively.
      Results: Sixty-seven out of 630 (10.63%) raw milk samples were positive for H.
      pylori. Ovine raw milk (17.27%) samples had the highest prevalence of H. pylori,
      while camel (5.00%) had the lowest. H. pylori strains harbored the highest
      prevalence of resistance against ampicillin (82.08%), tetracycline (76.11%),
      amoxicillin (74.62%), metronidazole (65.67%) and erythromycin (53.73%).
      Prevalence of resistance against more than 10 types of antibiotics was 17.91%.
      VacA s1a (83.58%), m1a (80.59%), s2 (77.61%) and m2 (68.65%), cagA (73.13%) and
      babA2 (44.77%) were the most commonly detected genotypes. We found that S1am1a
      (56.71%), s2m1a (56.71%), s1 am2 (43.28%) and s2 m2 (43.28%) were the most
      commonly detected genotyping pattern. Frequency of cagA-, oipA- and babA2-
      genotypes were 26.86%, 62.68% and 55.22%, respectively. We found that
      S1a/cagA+/iceA1/oipA-/babA2- (28.35%), m1a/cagA+/iceA1/oipA-/babA2- (28.35%) and
      s2/cagA+/iceA1/oipA-/babA2- (26.86%) were the most commonly detected combined
      genotyping pattern. Conclusions: Simultaneous presence of vacA, cagA, iceA, oipA
      and babA2 genotypes in antibiotic resistant H. pylori strains indicates important
      public health issue regarding the consumption of raw milk. However, additional
      researches are required to find molecular genetic homology and other
      epidemiological aspects of H. pylori in milk.

PMID- 30288256
TI  - Factors associated with bacteraemia due to multidrug-resistant organisms among
      bacteraemic patients with multidrug-resistant organism carriage: a case control
      study.
AB  - Background: Infections caused by multidrug-resistant organisms (MDRO) are
      emerging worldwide. Physicians are increasingly faced with the question of
      whether patients need empiric antibiotic treatment covering these pathogens. This
      question is especially essential among MDRO carriers. We aim to determine the
      occurrence of MDRO bacteraemia among bacteraemic patients colonized with MDRO,
      and the associated factors with MDRO bacteraemia among this population. Methods:
      We performed a retrospective monocentric study among MDRO carriers hospitalized
      with bacteraemia between January 2013 and August 2016 in a French hospital. We
      compared characteristics of patients with MDRO and non-MDRO bacteraemia. Results:
      Overall, 368 episodes of bacteraemia were reviewed; 98/368 (26.6%) occurred among
      MDRO carriers.Main colonizing bacteria were extended-spectrum beta-lactamase
      (ESBL)-producing Escherichia coli (40/98; 40.8%), ESBL-producing Klebsiella
      pneumoniae (35/98; 35.7%); methicillin-resistant Staphylococcus aureus (26/98;
      26.5%) and multidrug-resistant Pseudomonas aeruginosa (PA) (12/98; 12.2%).There
      was no significant difference considering population with MDRO bacteraemia vs.
      non-MDRO bacteraemia, except for immunosuppression [OR 2.86; p = 0.0207],
      severity of the episode [OR 3.13; p = 0.0232], carriage of PA [OR 5.24; p =
      0.0395], and hospital-acquired infection [OR 2.49; p = 0.034].In the multivariate
      analysis, factors significantly associated with MDRO bacteraemia among colonized
      patient were only immunosuppression [OR = 2.96; p = 0.0354] and the hospital
      acquired origin of bacteraemia [OR = 2.62; p = 0.0427]. Conclusions: According to
      our study, occurrence of bacteraemia due to MDRO among MDRO carriers was high.
      Factors associated with MDRO bacteraemia were severity of the episode and
      hospital-acquired origin of the bacteraemia. Thus, during bacteraemia among
      patients colonized with MDRO, if such characteristics are present, broad-spectrum
      antimicrobial treatment is recommended.

PMID- 30288258
TI  - Why do people choose nephrology? Identifying positive motivators to aid
      recruitment and retention.
AB  - Increasing concerns about recruitment and retention of junior doctors have led to
      renewed interest in how and when trainees choose their specialties. To our
      knowledge, no study has yet reported what attracts UK applicants to nephrology
      nor how clinicians develop vocational interests or make occupational choices.
      With this in mind, we sought to explore the motivation behind current
      nephrologist's career choices in the UK. We interviewed 11 nephrologists using a
      semi-structured face-to-face approach and used interpretative phenomenological
      analysis to conduct and analyse the interviews. We found role models were pivotal
      in encouraging specialization in nephrology, particularly those encountered in
      early postgraduate training. The diversity, diagnostic challenge and cross
      specialty knowledge was highlighted as well as the ability to 'make a difference
      to patients' lives'. Nephrologists enjoyed the challenge of managing very sick,
      acutely unwell patients as well as the holistic continuity of long-term care
      offered to dialysis patients and their families. Academic and procedural
      components were attractive motivators to the specialty and the flexibility to
      have multiple interests was noted, with many nephrologists having 'portfolio'
      careers. Based on these results, we suggest strategies the specialty can use to
      aid policy decision making, promote recruitment and improve educational
      experiences within current training programmes.

PMID- 30288257
TI  - Send more data: a systematic review of mathematical models of antimicrobial
      resistance.
AB  - Background: Antimicrobial resistance is a global health problem that demands all
      possible means to control it. Mathematical modelling is a valuable tool for
      understanding the mechanisms of AMR development and spread, and can help us to
      investigate and propose novel control strategies. However, it is of vital
      importance that mathematical models have a broad utility, which can be assured if
      good modelling practice is followed. Objective: The objective of this study was
      to provide a comprehensive systematic review of published models of AMR
      development and spread. Furthermore, the study aimed to identify gaps in the
      knowledge required to develop useful models. Methods: The review comprised a
      comprehensive literature search with 38 selected studies. Information was
      extracted from the selected papers using an adaptation of previously published
      frameworks, and was evaluated using the TRACE good modelling practice guidelines.
      Results: None of the selected papers fulfilled the TRACE guidelines. We recommend
      that future mathematical models should: a) model the biological processes
      mechanistically, b) incorporate uncertainty and variability in the system using
      stochastic modelling, c) include a sensitivity analysis and model external and
      internal validation. Conclusion: Many mathematical models of AMR development and
      spread exist. There is still a lack of knowledge about antimicrobial resistance,
      which restricts the development of useful mathematical models.

PMID- 30288260
TI  - Acute kidney injury in children with nephrotic syndrome: a single-center study.
AB  - Background: Children with nephrotic syndrome (NS) are at risk for the development
      of acute kidney injury (AKI) through a variety of mechanisms.The frequency of NS
      hospitalizations complicated by AKI has almost doubled in the last decade.
      Children with AKI have longer hospital length of stay and increased need for
      intensive care unit admission. The main objectives of this study were to
      determine the incidence, clinical characteristics, risk factors and short-term
      outcome of AKI in children hospitalized with NS. Methods: In this retrospective
      study, 355 children <=18 years of age with a clinical diagnosis of NS admitted in
      the Department of Nephrology, Gauhati Medical College and Hospital from January
      2012 to December 2015 were reviewed. Results: The incidence of AKI in children
      with NS was found to be 23.66%, 11.24%, 7.95% and 4.48% of children entered
      Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE) Stages R,
      I and F, respectively. Infection {odds ratio [OR] 2.53 [95% confidence interval
      (CI) 1.52-4.22]} and nephrotoxic medication exposure [OR 7.8 (95% CI 4.06-15.01)]
      were common factors associated with AKI. Children with steroid-dependent NS
      (SDNS) and steroid-resistant NS (SRNS) were more likely to develop AKI compared
      with children with steroid-sensitive NS (SSNS). The mean time to recovery for
      groups pRIFLE Stages R, I and F were 15 +/- 2 , 22 +/- 3 and 28 +/- 5 days,
      respectively. Children with NS who were hypertensive, had higher urinary protein
      excretion and low serum albumin were more prone to develop AKI. Conclusions: AKI
      is not uncommon in children with NS. Infection and exposure to nephrotoxic drugs
      are common factors associated with AKI. AKI is more frequent in SDNS and SRNS
      compared with SSNS. The mean time to recovery is prolonged with more severe AKI.

PMID- 30288259
TI  - Haemodynamic or metabolic stimulation tests to reveal the renal functional
      response: requiem or revival?
AB  - Renal stimulation tests document the dynamic response of the glomerular
      filtration rate (GFR) after a single or a combination of stimuli, such as an
      intravenous infusion of dopamine or amino acids or an oral protein meal. The
      increment of the GFR above the unstimulated state has formerly been called the
      renal functional reserve (RFR). Although the concept of a renal reserve capacity
      has not withstood scientific scrutiny, the literature documenting renal
      stimulation merits renewed interest. An absent or a blunted response of the GFR
      after a stimulus indicates lost or diseased nephrons. This information is
      valuable in preventing, diagnosing and prognosticating acute kidney injury and
      pregnancy-related renal events as well as chronic kidney disease. However, before
      renal function testing is universally practiced, some shortcomings must be
      addressed. First, a common nomenclature should be decided upon. The expression of
      RFR should be replaced by renal functional response. Second, a simple protocol
      must be developed and propagated. Third, we suggest designing prospective studies
      linking a defective stimulatory response to emergence of renal injury biomarkers,
      to histological or morphological renal abnormalities and to adverse renal
      outcomes in different renal syndromes.

PMID- 30288262
TI  - Severe tubulointerstitial nephritis: tracking tuberculosis even in the absence of
      renal granuloma.
AB  - Extra-pulmonary tuberculosis is frequently located in the kidneys and, in such
      cases, could be associated with a granulomatous interstitial nephritis.
      Granulomas are not always detected, especially in human immunodeficiency virus
      (HIV)-positive patients. We report here a case of tubulointerstitial nephritis
      without granulomas in an HIV-negative patient. Since all laboratory tests failed
      to isolate Mycobacterium tuberculosis in the kidney, a targeted biopsy guided by
      positron emission tomography-computed tomography was performed on a mediastinal
      node, revealing a positive culture. After 6 months of treatment, no recovery of
      the renal injury has been observed.

PMID- 30288261
TI  - De novo antineutrophil cytoplasmic antibody-associated vasculitis in pregnancy: a
      systematic review on maternal, pregnancy and fetal outcomes.
AB  - Background: De novo antineutrophil cytoplasmic antibody-associated vasculitis
      typically arises in post-reproductive years, but can occur during pregnancy.
      Concerns of treatment-related teratogenicity persist, while efficacy and safety
      of new therapies including intravenous immunoglobulin (IVIG) and rituximab are
      uncertain. There remains a paucity of maternal, fetal and pregnancy outcome data
      in these women, and therefore a lack of guidance on safe treatment for
      clinicians. Methods: We conducted a systematic review of the literature and a
      local, retrospective chart review of women with de novo antibody-associated
      vasculitis (AAV) in pregnancy. Cochrane, Embase and PubMed databases and relevant
      conference abstracts were searched. Patient demographics, clinical presentation,
      management and outcomes (maternal, fetal and pregnancy-related) were analyzed.
      Results: Twenty-seven cases of de novo AAV in pregnancy were included. Women
      presented were from 5 to 39 weeks' gestation, of which a majority were in the
      second trimester (median 20 weeks). The median gravida of women was 2 and the
      median parity was 1. Women were treated with steroids (89%), cyclophosphamide
      (CYC) (37%), other immunosuppressive agents [azathioprine (AZA), IVIG, plasma
      exchange (PLEX)] or no therapy (11%). High rates of serious complications,
      including preeclampsia (29%) and maternal death (7%), were reported; however,
      most pregnancies resulted in live birth (73%). Prematurity was common; 73% of
      live births occurred prior to 37 weeks' gestation and 40% prior to 34 weeks'
      gestation. The majority of infants were born in the third trimester (median 34.5
      weeks). Rates of pregnancy termination were high (23%) and only one intrauterine
      death was reported, shortly after initiation of therapy (4%). Congenital
      abnormalities were rare, with one infant having a solitary, pelvic kidney (6%)
      after maternal treatment with steroids, CYC and PLEX. Use of PLEX, IVIG and AZA
      increased after 2005, whereas CYC use decreased. Remission often occurred
      postpartum (60%). Conclusions: De novo AAV in pregnancy can result in
      uncomplicated pregnancies; however, serious maternal risks exist. Further data on
      potentially pregnancy compatible therapies such as IVIG and rituximab are needed
      in this population.

PMID- 30288263
TI  - Renal involvement in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed adult leukemia
      in the USA and Western Europe. Kidney disease can present in patients with CLL as
      a manifestation of the disease process such as acute kidney injury with
      infiltration or with a paraneoplastic glomerular disease or as a manifestation of
      extra renal obstruction and tumor lysis syndrome. In the current era of novel
      targeted therapies, kidney disease can also present as a complication of
      treatment. Tumor lysis syndrome associated with novel agents such as the B-cell
      lymphoma 2 inhibitor venetoclax and the monoclonal antibody obinutuzumab are
      important nephrotoxicities associated with these agents. Here we review the
      various forms of kidney diseases associated with CLL and its therapies.

PMID- 30288264
TI  - Is renal tubular cadmium toxicity clinically relevant?
AB  - Background: Exposure to cadmium (Cd) has been associated with the development of
      hypertension, especially in women, but the mechanism of such an association is
      not understood. We hypothesize that Cd exposure alters renal production of 20
      hydroxyeicosatetraenoic acid (20-HETE), which plays an indispensable role in
      renal salt balance and blood pressure control. Methods: We examined long-term Cd
      exposure in relation to urinary 20-HETE excretion levels, tubular dysfunction and
      blood pressure measures, using data from a population-based, cross-sectional
      study that included 115 normotensive and 110 hypertensive women, 33-55 years of
      age, who lived in Cd contamination areas in Thailand. Results: The mean [standard
      deviation (SD)] blood Cd level of the study subjects was 3.57 (3.3) ug/L, while
      the mean (SD) urinary Cd and urinary 20-HETE levels were 0.58 (0.47) ug/g
      creatinine and 1651 (4793) pg/mL, respectively. Elevated 20-HETE levels were
      associated with a 90% increase in prevalence odds of hypertension (P = 0.029),
      four times greater odds of having higher urinary Cd levels (P = 0.030) and a 53%
      increase in odds of having higher levels of tubular dysfunction (P = 0.049),
      evident from an increase in urinary excretion of beta2-microglobulin. In
      normotensive subjects, an increase in urinary 20-HETE levels from tertile 1 to
      tertile 3 was associated with a systolic blood pressure increase of 6 mmHg (95%
      confidence interval 0.3-12, P = 0.040). Conclusions: This is the first report
      that links urinary 20-HETE levels to blood pressure increases in Cd-exposed
      women, thereby providing a plausible mechanism for associated development of
      hypertension.

PMID- 30288266
TI  - Multi-intervention management of calcific uremic arteriolopathy in 24 patients.
AB  - Background: Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is
      a rare but life-threatening condition predominately occurring in patients with
      end-stage renal disease on dialysis. In the absence of randomized clinical trials
      to guide management, clinicians must rely on observational data. We have
      previously reported the outcomes of our multi-intervention management in seven
      patients and now present a larger series of patients with extended follow-up.
      Methods: We performed a retrospective analysis of all patients diagnosed with CUA
      at a single academic center between 2008 and 2017. We identified 24 patients
      including 13 hemodialysis, 8 peritoneal dialysis and 3 predialysis Stage 5
      chronic kidney disease patients. Results: Mean age at diagnosis was 60.5 years
      (range 35-83) and mean follow-up 30.5 months (range <1-99). Patients were
      predominately female (71%) and Caucasian (83%) with diabetes mellitus diagnosed
      in 16 of 24 patients. Fifteen of 24 patients had ulcerating lesions suggestive of
      advanced disease and 20 of 24 had extensive involvement (bilateral disease or
      lesion size >5 cm). Treatment consisted of intensive hemodialysis (>20 h per
      week), sodium thiosulfate, wound care, analgesics and discontinuation of trigger
      medications including warfarin. Hyperbaric oxygen, cinacalcet, bisphosphonates
      and vitamin K were used in some cases. Overall 1 year mortality was 41% (9/22)
      and overall mortality at the end of follow-up was 64% (14/24). Cause of death was
      felt to be attributable to CUA in only four cases (16.7%). Complete or partial
      resolution of lesions occurred in 17 of 24 patients. One patient had recurrence
      of CUA 20 months after initial diagnosis. Conclusions: Although mortality remains
      high in this group, direct CUA-attributable mortality is lower than historic
      reports. We conclude that a multi-intervention approach can be successful in
      treating a group of patients with severe CUA lesions.

PMID- 30288265
TI  - The metabolomic quest for a biomarker in chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a growing burden on people and on healthcare for
      which the diagnostics are niether disease-specific nor indicative of progression.
      Biomarkers are sought to enable clinicians to offer more appropriate patient
      centred treatments, which could come to fruition by using a metabolomics
      approach. This mini-review highlights the current literature of metabolomics and
      CKD, and suggests additional factors that need to be considered in this quest for
      a biomarker, namely the diet and the gut microbiome, for more meaningful advances
      to be made.

PMID- 30288267
TI  - Achievement of 2009 and 2017 Kidney Disease: Improving Global Outcomes mineral
      and bone targets and survival in a French cohort of chronic kidney disease Stages
      4 and 5 non-dialysis patients.
AB  - Background: The aim of the third French Phosphorus and Calcium Observatory (Photo
      Graphe(r) 3) was to assess the achievement of international Kidney Disease:
      Improving Global Outcomes (KDIGO) recommendations on optimal serum phosphate,
      calcium and parathyroid hormone (PTH) levels and possible associations with
      mortality in patients with chronic kidney disease (CKD). Methods: This was a
      prospective, observational study conducted with nephrologists in France who were
      selected using a clustering approach. Adult patients with non-dialysis Stage 4 or
      5 CKD and no kidney graft history were eligible. Data about clinical events,
      serum biochemistry and treatment were collected every 6 months for 2.5 years and
      12 months thereafter. The Kaplan-Meier method was used for survival analysis and
      Cox proportional hazards model for identification of factors associated with
      survival. Results: Overall, 566 CKD Stage 4 patients (men, 56%) and 153 CKD Stage
      5 patients (men, 62%) were included. In Stage 4, only 14-15% patients achieved
      the three main 2009 KDIGO targets during the first 2 years and 22% at 2.5 years.
      In Stage 5 patients, the proportion remained <6% throughout. The percentages of
      patients achieving the three main 2017 KDIGO targets were slightly higher at each
      time point. Overall, 14% of Stage 4 and 10% of Stage 5 patients died in the
      observation period. Only age and haemoglobin level were significantly associated
      with risk of all-cause mortality. Conclusions: Few CKD patients achieved KDIGO
      mineral targets. Increased mortality risk was linked to older age and lower
      haemoglobin level, but not to serum calcium, phosphate or PTH targets.

PMID- 30288268
TI  - Using manual exchanges for an urgent-start peritoneal dialysis program.
AB  - Background: Urgent-start peritoneal dialysis (USPD) was designed to avoid
      temporary hemodialysis initiation with a hemodialysis catheter. In these
      patients, PD is initiated within 2 weeks of catheter placement, but typically
      these prescriptions utilize automated peritoneal dialysis (APD) with a cycler.
      Manual exchanges have not been reported previously for USPD. We hypothesize that
      using multiple, low-volume manual exchanges, patients will have similar rates of
      peritonitis, exit-site infection (ESI), pericatheter leaks and discontinuation of
      PD in the first 3 months after initiation. Methods: This retrospective study
      included patients who initiated PD in our unit from May 2014 until August 2016
      using our USPD protocol. Patients with a body surface area <1.7 m2 used 750 mL
      dwell volumes and those >1.7 m2 used 1000 mL dwell volumes during the first 7
      days. Dwell times were 2-2.5 h for two to three exchanges per day. After 7 days
      of successful therapy, the dwell volumes were doubled. All patients were
      maintained on furosemide 160 mg twice daily. Results: There were 20 patients
      enrolled in our USPD program. Our rates of peritonitis, ESI, pericatheter leak
      and discontinuation of PD were 5%, 0%, 5% and 5%, respectively. Conclusions:
      Manual exchange during USPD is a viable modality with similar results as APD.
      Using manual exchanges allows patients to be more ambulatory during the day when
      they are not dwelling, allows nurses to evaluate the amount of ultrafiltration
      and effluent characteristics and allows for training in manual exchanges as well.

PMID- 30288269
TI  - Peritoneal dialysis catheter leakage following intermittent vacuum therapy.
AB  - Peripheral arterial disease and diabetic foot syndrome are common comorbidities
      in dialysis patients. These conditions are treated with intermittent vacuum
      therapy in order to increase angiogenesis and perfusion. Some devices encase the
      lower extremities up to the abdomen. Here we report the case of a patient who had
      performed peritoneal dialysis for 2 years without complications. Following
      postoperative intermittent vacuum therapy, he presented with extensive catheter
      leakage. Ultimately the patient had to be switched to haemodialysis and the
      catheter had to be removed. This case exemplifies that peritoneal dialysis
      patients have a substantial risk for noninfectious catheter-related complications
      using vacuum therapy.

PMID- 30288271
TI  - Correlation between Dt/V derived from ionic dialysance and blood-driven Kt/V of
      urea in African-American hemodialysis patients, based on body weight and
      ultrafiltration volume.
AB  - Background: The Dt/V obtained by using ionic dialysance (D) as a surrogate for
      urea clearance (K) is a well-validated adjunct measure of hemodialysis adequacy,
      with a variable level of correlation with urea-based Kt/V. However, this
      correlation has not been examined based on patients' body size and
      ultrafiltration (UF) volume during the dialysis session. Methods: Simultaneous
      evaluations of online Dt/V and single-pool variable-volume urea Kt/V were made.
      Patients were categorized into three subgroups based on their weight (<60, 60-80
      and >=80 kg), body mass index (<25, 25-30 and >30 kg/m2) and UF volume (<1.5, 1.5
      3 and >3 L). The correlation between Dt/V and Kt/V was evaluated for the entire
      cohort per dialysis session in each subgroup. Results: Mean Kt/V was greater than
      the mean Dt/V (1.72 versus 1.50, P < 0.001), with an overall correlation r value
      of 0.602. This correlation was stronger in the medium weight group versus lower
      and higher weights. The correlation between Dt/V and Kt/V was inversely related
      to the UF volume (r = 0.698, 0.621 and 0.558 for those with UF volume of <1.5,
      1.5-3.0 and >3 L, respectively). A total of 99.3% of patients with Dt/V of >1.2
      also had Kt/V >1.2 and 9.5% of those with Dt/V <1.2 had their Kt/V <1.2.
      Conclusions: There is a moderate degree of correlation between Dt/V and Kt/V in
      African-American hemodialysis patients, which is impacted by body size and UF
      volume. A Dt/V of >1.2 strongly predicts adequate dialysis as defined by Kt/V of
      >1.2.

PMID- 30288270
TI  - Cost of hemodialysis in a public sector tertiary hospital of India.
AB  - Introduction: Nearly 220000 patients are diagnosed with end-stage renal disease
      (ESRD) every year, which calls for an additional demand of 34 million dialysis
      sessions in India. The government of India has announced a National Dialysis
      Programme to provide for free dialysis in public hospitals. In this article we
      estimate the overall cost of performing hemodialysis (HD) in a tertiary care
      hospital. Second, we assess the catastrophic impact of out-of-pocket expenditures
      (OOPEs) for HD on households and its determinants. Methods: The economic health
      system cost of HD was estimated using bottom-up costing methods. All resources,
      capital and recurrent, utilized for service delivery from April 2015 to March
      2016 were identified, measured and valued. Capital costs were annualized after
      accounting for their useful life and discounting at 3% for future years.
      Sensitivity analyses were undertaken to determine the effect of variation in the
      input prices and other assumptions on the annual health system cost. OOPEs were
      assessed by interviewing 108 patients undergoing HD in the study hospital to
      account for costs from the patient's perspective. The prevalence of catastrophic
      health expenditures (CHEs) was computed per threshold of 40% of non-food
      expenditures. Results: The overall average cost incurred by the health system per
      HD session was INR 4148 (US$64). Adjusting for capacity utilization, the health
      system incurred INR 3025 (US$47) per HD at 100% bed occupancy. The mean OOPE per
      patient per session was INR 2838 (US$44; 95% confidence interval US$34-55). The
      major components of this OOPE were medicines and consumables (64.1%). The
      prevalence of a CHE per HD session was 11.1%. Conclusion: Our study findings
      would be useful in the context of planning for dialysis services, setting
      provider payment rates for dialysis under various publicly sponsored health
      insurance schemes and undertaking future cost-effectiveness analysis to guide
      resource allocation decisions.

PMID- 30288272
TI  - Evaluation of the efficacy of a medium cut-off dialyser and comparison with other
      high-flux dialysers in conventional haemodialysis and online haemodiafiltration.
AB  - Background: Online haemodiafiltration (OL-HDF) has been shown to reduce all-cause
      mortality versus conventional haemodialysis (HD); however, it is not always
      available. In these situations, a novel class of membranes with a higher pore
      size, medium cut-off (MCO) dialysers, could be promising. The aim of this study
      is to evaluate the efficacy of an MCO dialyser in the removal of small and medium
      size molecules and compare it with standard high-flux (HF) dialysers in HD and OL
      HDF. Methods: In this crossover study, 18 prevalent HD patients were studied in
      three single mid-week dialysis treatments during three consecutive weeks as
      follows: first week with OL-HDF with a standard HF dialyser, second week with
      conventional HD with a standard HF dialyser and third week with conventional HD
      with an MCO dialyser. Reduction ratios (RRs) of different-sized molecules and
      albumin losses were collected for the different dialysers. Results: MCO HD
      provided a greater reduction of middle and larger middle molecules compared with
      standard HF HD [rate reduction (RR) beta2-microglobulin 74.7% versus 69.7%,
      P=0.01; RR myoglobin 62.5% versus 34.3%, P=0.001; RR prolactin 60% versus 32.8%,
      P=0.001; RR alpha1-glycoprotein 2.8% versus -0.1%, P=0.01]. We found no
      difference in the clearance of small and larger middle molecules comparing MCO HD
      with OL-HDF. Albumin losses were 0.03  g/session with MCO HD and 3.1  g/session
      with OL-HDF (P=0.001). Conclusion: MCO HD is superior to standard HF HD in the
      removal of middle and larger middle molecules and it is not inferior to OL-HDF in
      the clearance of small and larger middle molecules. Thus it could be an
      alternative in patients in which it is not possible to perform OL-HDF.

PMID- 30288273
TI  - Expert opinion for use of faecal calprotectin in diagnosis and monitoring of
      inflammatory bowel disease in daily clinical practice.
AB  - Background: Despite many publications regarding the role of faecal calprotectin
      (FC) in inflammatory bowel disease (IBD), clear recommendations for its use in
      clinical practice are currently lacking in the literature. Aim: The aim of this
      article is to provide practical guidance for clinicians for the use of FC in the
      detection and management of patients with IBD. Methods: All relevant publications
      were analysed and practical statements were proposed based on a Delphi consensus
      approach. Results: Different commercial assays have been developed but
      international standardisation is lacking. FC can help in the diagnosis process of
      IBD. In IBD, FC can predict response to therapy, detect subclinical inflammation
      and help to drive treatment decisions to achieve better endoscopic and clinical
      outcomes. After Crohn's surgery FC can identify patients with early endoscopic
      recurrence. Conclusion: Although major therapeutic changes should not be based on
      FC alone, FC is a valuable tool to optimise the care for IBD patients.

PMID- 30288274
TI  - New developments in the treatment of opioid-induced gastrointestinal symptoms.
AB  - Chronic pain affects a large part of the global population, leading to an
      increase of opioid use. Opioid-induced constipation (OIC), a highly prevalent
      adverse effect of opioid use, has a major impact on patients' quality of life.
      Thanks to the introduction of new drugs for chronic constipation, which can also
      be used in OIC, and the development of peripherally acting mu-opioid receptor
      blockers, specifically for use in OIC, therapeutic options have seen major
      development. This review summarises current and emerging treatment options for
      OIC based on an extensive bibliographical search. Efficacy data for laxatives,
      lubiprostone, prucalopride, linaclotide, oxycodone/naloxone combinations,
      methylnaltrexone, alvimopan, naloxegol, naldemedine, axelopran, and bevenopran in
      OIC are summarised.

PMID- 30288275
TI  - Diabetes is an independent risk factor for delayed perforation after foreign
      bodies impacted in esophagus in adults.
AB  - Background: Perforation is the most serious complication of esophageal foreign
      bodies. Studies examining the association between diabetes and esophageal foreign
      body-induced perforation are largely non-existent. Objectives: The purpose of
      this study was to identify the risk factors for esophageal foreign body-induced
      perforation. Methods: A retrospective chart review of patients with esophageal
      foreign bodies between January 2012-January 2017 was performed at the Chinese
      People's Liberation Army General Hospital. The patients were divided into two
      groups: those complicated with perforation and those without perforation. Date on
      patient demographics, symptoms, foreign bodies, and diabetes were collected and
      analyzed. Study-specific odds ratio and 95% confidence intervals (CI) were
      estimated using multivariable logistic regression models. Results: Of 294
      patients with esophageal foreign bodies (41.84% male, mean age, 56.73 years), 33
      (11.22%) complicated by perforation. Diabetes (odds ratio = 6.00; 95% confidence
      interval = 1.72-20.23), duration (>24 h) of foreign bodies retention (odds ratio
      = 4.25; 95% confidence interval = 1.71-10.86), and preoperative fever (odds ratio
      = 8.19; 95% confidence interval = 3.17-21.74) were strongly associated with an
      increased risk of perforation, whereas the sensation of a foreign body (odds
      ratio = 0.32; 95% confidence interval = 0.09-0.92) was a protective factor of
      perforation. Glucose level was not observed to have an association among patients
      with or without perforation. Conclusions: Diabetes and duration of foreign body
      retention increase risk for esophageal foreign bodies complicated by perforation,
      and cases with elevated armpit temperature may represented a more likely
      perforation compared with those without fever.

PMID- 30288276
TI  - Physical activity, sedentary behaviour and risk of oesophago-gastric cancer: A
      prospective cohort study within UK Biobank.
AB  - Background: Few observational studies have assessed the role of physical activity
      in oesophago-gastric cancer risk. Objective: This prospective cohort study aimed
      to assess the association between physical activity and risk of oesophageal or
      gastric cancer. Methods: A cohort of 359,033 adults aged 40-69 years were
      identified from the UK Biobank, which recruited participants between 2006 and
      2010. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the
      associations between self-reported levels of physical activity and screen-based
      sedentary behaviour and risk of oesophageal and gastric cancer were calculated
      using Cox proportional hazards models. Results: During eight years of follow-up
      (mean = 5.5), 294 oesophageal cancer and 217 gastric cancer cases were
      identified. Physical activity and screen-based sedentary behaviour levels were
      not associated with overall oesophago-gastric cancer risk. However, when compared
      with low levels, high physical activity levels were associated with a
      significantly reduced risk of gastric non-cardia cancer (HR 0.58, 95% CI 0.37
      0.95). Moderate physical activity levels were associated with a 38% reduced risk
      of oesophageal adenocarcinoma (HR 0.62, 95% CI 0.43-0.89), although no dose
      response association was apparent. Conclusion: Moderate, rather than high,
      physical activity levels were associated with the strongest reductions in
      oesophageal adenocarcinoma risk in this large UK prospective cohort.

PMID- 30288277
TI  - Nitrous oxide cryotherapy ablation for refractory gastric antral vascular
      ectasia.
AB  - Background: Argon plasma coagulation (APC) is typically the first-line therapy
      for gastric antral vascular ectasia (GAVE). However, many patients are refractory
      to APC ablation. Objective: We examined the safety and efficacy of nitrous oxide
      CryoBalloon cryotherapy ablation for GAVE refractory to APC. Methods: This is a
      retrospective review of patients with refractory GAVE treated with the
      CryoBalloon system. Technical success was defined as successful ablation of the
      visualized GAVE. Clinical success was defined by transfusion independence and
      percentage of GAVE that was eradicated. Results: Twenty-three patients with GAVE
      were included, of whom 16 patients (70%) had two treatments with the CryoBalloon
      and seven patients (30%) had one treatment. Technical success was achieved in all
      patients. At six months, 19/23 (83%) were transfusion independent, while 20/23
      (87%) had more than 75% of the GAVE eradicated. Patients were transfused an
      average of 1.8 units/month one year prior to cryotherapy and an average of 0.3
      units/month up to six months post-cryotherapy (p < 0.001). The average increase
      in mean hemoglobin at six months was 2.55 g/dl. No acute or late adverse events
      were reported. Conclusions: CryoBalloon ablation is an efficacious and safe
      modality for the treatment of GAVE. Prospective studies need to be conducted to
      determine comparative results to standard therapies.

PMID- 30288278
TI  - Risk factors associated with osteoporosis in a cohort of prospectively diagnosed
      adult coeliac patients.
AB  - Background: Up to 75% of patients with untreated coeliac disease (CD) present
      with osteopenia or osteoporosis. Guidelines do not express with certainty whether
      each patient with newly diagnosed CD should undergo a dual-energy x-ray
      absorptiometry (DEXA) scan. Aim: The aim of this article is to evaluate the
      prevalence of bone mineral density (BMD) alterations at diagnosis and risk
      factors associated with osteoporosis. Methods: A total of 214 adult patients
      (median age 38 years; female = 71.5%) newly diagnosed with CD underwent DEXA. The
      patients were divided into three groups: patients with normal BMD, those with
      osteopenia and those with osteoporosis. Clinical, histological and serological
      features were assessed and compared among the three groups. Logistic regression
      including relevant independent variables was performed. Results: DEXA indicated
      that 39.7%, 42.5% and 17.8% of the CD patients had normal BMD, osteopenia and
      osteoporosis, respectively. Logistic regression indicated that features
      significantly associated with osteoporosis were male gender (OR 4.7; 95%CI 1.1 to
      20.8), age >=45 years (OR 6.5; 95% CI 1.3 to 32.2), underweight (OR 7.4; 95% CI
      1.3 to 42.5) and greater histological damage (Marsh 3C; OR 5.8; 95% CI 1.4 to
      24.1). Conclusions: BMD alterations were found in 60.3% of newly diagnosed adult
      coeliac patients. Osteoporosis was significantly associated with age >=45 years,
      male gender, underweight and Marsh 3C, suggesting that at CD diagnosis, a DEXA
      scan might be beneficial, particularly in these subgroups of patients.

PMID- 30288279
TI  - The etiology of potential small-bowel bleeding depending on patient's age and
      gender.
AB  - Background: Whether the etiology of potential small-bowel bleeding depends on the
      age and gender of the patient is not yet fully understood. Methods: A total of
      1953 patients who underwent video capsule endoscopy (VCE) to evaluate potential
      small-bowel bleeding and were registered in the Capsule Endoscopy Nationwide
      Database Registry from 2003 to 2014 were eligible for this study. VCE findings
      and the etiology of small-bowel bleeding were analyzed by age and gender.
      Results: The diagnostic yield of VCE was 48.4% (95% CI: 46.2%-50.6%) and the
      diagnosis rate of etiology of potential small-bowel bleeding was 61.4% (95% CI:
      59.2%-63.6%). The etiology of potential small-bowel bleeding depends on the age
      and gender of the patient. Crohn's disease and small-bowel diverticular diseases
      were more prevalent etiology of potential small-bowel bleeding in the young
      adults group (< 40 years) whereas angiodysplasia was revealed to be a most common
      etiology in elderly group (>= 60 years), reaching statistical significance
      (p<0.00152) by Bonferroni correction. Conclusions: The etiology of potential
      small-bowel bleeding depends on the age of the patient. Thus, an individualized
      lesion-specific diagnostic approach based on age might be needed for patients
      with potential small-bowel bleeding.

PMID- 30288280
TI  - Association of proton pump inhibitors with the risk of hepatic encephalopathy
      during hospitalization for liver cirrhosis.
AB  - Background: Hepatic encephalopathy is associated with altered gut microbiota.
      Proton pump inhibitors increase the risk of small bowel bacterial overgrowth.
      Objectives: This was a case-control study aimed at exploring the relationship of
      proton pump inhibitor use with the risk of hepatic encephalopathy during
      hospitalization in liver cirrhosis. Methods: Case and control groups were defined
      as cirrhotic patients who developed hepatic encephalopathy during hospitalization
      and those without hepatic encephalopathy at admission or during hospitalization,
      respectively. Age, gender, and Child-Pugh score were matched between the groups.
      Odds ratios with 95% confidence intervals were calculated to express the
      association of proton pump inhibitors with the risk of hepatic encephalopathy.
      Four subgroup analyses were performed after excluding patients with acute upper
      gastrointestinal bleeding, infections, and in-hospital death, and after matching
      model for end-stage liver disease score. Results: In the overall analysis, 128
      patients were included in each group of cases and controls. The proportion of
      proton pump inhibitor use was significantly higher in the case group than the
      control group (79.7% vs 43%, p < 0.001). Proton pump inhibitor use (odds ratio =
      3.481, 95% confidence interval: 1.651-7.340, p = 0.001) was independently
      associated with the development of hepatic encephalopathy in the multivariate
      analysis. In the four subgroup analyses, proton pump inhibitor use remained
      independently associated with the risk of hepatic encephalopathy. Conclusion:
      Proton pump inhibitor use might increase the risk of hepatic encephalopathy
      during hospitalization.

PMID- 30288282
TI  - Terlipressin for variceal bleeding induces large plasma sodium fluctuations in
      patients without cirrhosis.
AB  - Background: Terlipressin is used as pharmacological treatment for variceal
      bleeding. The drug's physiological effect favours hyponatremia, and rapid changes
      in plasma sodium (PNa) may cause brain injury. Cirrhosis patients seem to be
      largely protected against this effect but patients without cirrhosis may not be
      so. Objective: The objective of this study was to examine whether terlipressin
      treatment of patients without cirrhosis leads to more serious fluctuations in PNa
      than in cirrhosis. Methods: In a retrospective cohort design, during a 39-month
      period, 11 patients with prehepatic portal hypertension and no cirrhosis and 134
      patients with cirrhosis received a minimum cumulative terlipressin dose of 4 mg
      during at least 24 hours for variceal bleeding. The groups' PNa changes were
      compared. Results: During terlipressin, the non-cirrhotic patients developed a
      greater reduction in PNa [mean 8.3 (95% confidence interval (CI) 1.9-14.6) vs.
      1.8 (1.0-2.7) mmol/l; p = 0.048], a lower nadir PNa [129 (123-135) vs. 133 (132
      134) mmol/l; p = 0.06], and within 48 hours after terlipressin a greater increase
      in PNa [12.6 (3.4-21.7) vs. 2.3 (1.5-3.0) mmol/l; p = 0.03]. Severe (>10 mmol/l
      change) hyponatriemia or PNa rebound were seen in 27% of these patients but in
      only 4% of those with cirrhosis (p = 0.02). One non-cirrhotic patient developed
      permanent brain damage. Conclusion: Terlipressin treatment of bleeding varices
      carries a high risk of potentially dangerous PNa fluctuations in patients with
      non-cirrhotic prehepatic portal hypertension.

PMID- 30288281
TI  - Long-term changes in liver elasticity in hepatitis C virus-infected patients with
      sustained virologic response after treatment with direct-acting antivirals.
AB  - Background: The use of interferon-free direct-acting antiviral agents (DAAs) is
      associated with a rapid short-term decrease in liver stiffness in chronic
      hepatitis C-infected patients with sustained virologic response (SVR). Objective:
      The objective of this article is to evaluate long-term changes in liver
      elasticity in hepatitis C patients with SVR using transient elastography (TE),
      FIB-4 and APRI. Methods: A total of 143 patients were treated with DAAs and
      reached SVR. Patients received TE measurement (median (range)) at treatment start
      (baseline), follow-up week 24 (FU24) and follow-up week 96 (FU96). Laboratory
      data were examined at each date and FIB-4 and APRI were calculated. Results:
      Liver elasticity showed a significant decrease from baseline to FU24 (13.1 (3.1
      75) kPa to 9.3 (2.9-69.1) kPa; p < 0.0001) and declined further until FU96 (7.9
      (2.4-59.3) kPa; p < 0.0001). Liver inflammation and liver function parameters
      normalised during long-term follow-up. Progression of liver stiffness between
      FU24 to FU96 despite viral clearance was observed in 24 patients (17%). Long-term
      liver stiffness progression was associated with aspartate aminotransferase levels
      and TE change from baseline to FU24. Conclusion: During long-term follow-up, the
      majority of patients with SVR had further improved liver stiffness values. Still,
      a significant proportion of patients may show long-term liver stiffness
      progression and thus continued TE follow-up is recommended.

PMID- 30288283
TI  - Statin use is not associated with an increased risk of acute pancreatitis-A meta
      analysis of observational studies.
AB  - Background: Statins are perceived as potential etiological factors for acute
      pancreatitis (AP), but recent evidence suggests the opposite. Our aim was to
      evaluate the association between statin use and risk of AP in observational
      studies. Methods: Medline, Scopus, and Web of Science were searched for cohort
      (C) and case-control (CC) studies evaluating statins as intervention and AP as
      outcome. Pooled adjusted odds ratios (ORs) with corresponding 95% confidence
      intervals (CIs) were calculated. Results: Thirteen studies (seven CC, six C) with
      34,899 AP patients and 5,377,894 controls were included. Prevalence of statin use
      was 9.8% among AP patients and 25% among controls. Pooled adjusted OR was 1.00
      (95% CI = 0.63 to 1.59) with considerable heterogeneity (I 2 = 98%). CC studies
      were associated with increased AP risk (OR = 1.33; 95% CI = 1.20 to 1.47), unlike
      C studies (OR = 0.69; 95% CI = 0.37 to 1.31). No association with increased risk
      was found for studies from Western countries (OR = 0.90; 95% CI = 0.52 to 1.56),
      unlike for studies conducted in Asia (OR = 1.39; 95% CI = 1.10 to 1.75).
      Conclusion: Statin use is not associated with increased risk of AP. Increased
      risk was limited to CC studies, which are more prone to bias, while C studies
      showed no global effect. Further research is needed to clarify whether statin
      type, dosage, treatment duration or AP etiology might account for this
      difference.

PMID- 30288284
TI  - Features of incident colorectal cancer in Lynch syndrome.
AB  - Background and objective: Despite intensive colonoscopic surveillance, a
      substantial proportion of Lynch syndrome (LS) patients develop colorectal cancer
      (CRC). The aim of this study was to characterize incident CRC in LS patients.
      Methods: All patients diagnosed with incident CRC after start of colonoscopic
      surveillance were identified in the Dutch LS Registry of 905 patients. A
      retrospective analysis of patient records was carried out for patient
      characteristics, survival, CRC characteristics and findings of previous
      colonoscopy. Results: Seventy-one patients (7.8%) were diagnosed with incident
      CRC. Median interval between incident CRC diagnosis and previous colonoscopy was
      23.8 (range 6.7-45.6) months. Median tumor diameter was 2.5 cm, and 17% of the
      tumors were sessile or flat. Most patients (83%) had no lymph node metastases.
      There was no association between tumor size and colonoscopy interval or lymph
      node status. Most patients (65%) had no adenomas during previous colonoscopy. Two
      patients (2.8%) eventually died from metastatic CRC. Conclusion: The high
      frequency of incident CRC in LS likely results from several factors. Our findings
      lend support to the hypothesis of fast conversion of adenomas to CRC, as 65% of
      patients had no report of polyps during previous colonoscopy. High-quality
      colonoscopies are essential, especially as tumors and adenomas are difficult to
      detect because of their frequent non-polypoid appearance. Early detection due to
      surveillance as well as the indolent growth of CRC, as demonstrated by the lack
      of lymph node metastases, contributes to the excellent survival observed.

PMID- 30288285
TI  - Fecal immunochemical test for hemoglobin in combination with fecal transferrin in
      colorectal cancer screening.
AB  - Objective: Fecal transferrin has been suggested as a complementary or even
      superior marker for early detection of colorectal cancer (CRC) besides fecal
      hemoglobin. We aimed to evaluate both markers individually and in combination in
      a large cohort of participants of screening colonoscopy. Methods: Precolonoscopy
      stool samples were obtained from participants of screening colonoscopy and frozen
      at -80C until blinded analysis, using a dual-quantitative fecal immunochemical
      test (FIT) for hemoglobin and transferrin. Sensitivity, specificity and area
      under the curve (AUC) were calculated for CRC and advanced adenoma (AA). Results:
      A total of 1667 participants fulfilled our inclusion criteria. All individuals
      with advanced neoplasm (AN) (16 CRC, 200 AA) and 300 randomly selected
      participants without AN were included. Mean age was 63 years and 56% were male.
      The AUC for CRC and AA was 92% and 68%, respectively, for hemoglobin vs. 79% and
      58%, respectively for transferrin. Combination of both markers yielded an AUC for
      CRC and AA of 92% and 68%, respectively. Conclusion: FIT for hemoglobin shows
      better diagnostic performance than FIT for transferrin for the detection of ANs
      (both proximal and distal neoplasms), and a combination of both markers does not
      improve the diagnostic performance.

PMID- 30288286
TI  - Efficacy of different faecal microbiota transplantation protocols for Clostridium
      difficile infection: A systematic review and meta-analysis.
AB  - Background: Protocols for treating recurrent Clostridium difficile infection
      (rCDI) through faecal microbiota transplantation (FMT) are still not
      standardised. Our aim was to evaluate the efficacy of different FMT protocols for
      rCDI according to routes, number of infusions and infused material. Methods:
      MEDLINE, Embase, SCOPUS, Web of Science and the Cochrane Library were searched
      through 31 May 2017. Studies offering multiple infusions if a single infusion
      failed to cure rCDI were included. Data were combined through a random effects
      meta-analysis. Results: Fifteen studies (1150 subjects) were analysed. Multiple
      infusions increased efficacy rates overall (76% versus 93%) and in each route of
      delivery (duodenal delivery: 73% with single infusion versus 81% with multiple
      infusions; capsule: 80% versus 92%; colonoscopy: 78% versus 98% and enema: 56%
      versus 92%). Duodenal delivery and colonoscopy were associated, respectively,
      with lower efficacy rates (p = 0.039) and higher efficacy rates (p = 0.006)
      overall. Faecal amount <= 50 g (p = 0.006) and enema (p = 0.019) were associated
      with lower efficacy rates after a single infusion. The use of fresh or frozen
      faeces did not influence outcomes. Conclusions: Routes, number of infusions and
      faecal dosage may influence efficacy rates of FMT for rCDI. These findings could
      help to optimise FMT protocols in clinical practice.

PMID- 30288287
TI  - Post-infectious IBS: Defining its clinical features and prognosis using an
      internet-based survey.
AB  - Background: Gastrointestinal infection is an important risk factor for developing
      irritable bowel syndrome (IBS). Our aim was to characterise post-infectious IBS
      (PI-IBS) compared to other IBS patients. Methods: An internet survey of IBS
      patients using Rome III diagnostic questionnaire, Hospital Anxiety and Depression
      Scale (HADS) and Patient Health Questionnaire-12 Somatic Symptom (PHQ12-SS) scale
      score documenting the mode of onset was conducted. Results: A total of 7811
      participants (63.2% female), of whom 1004 (13.3%) met criteria for PI-IBS, were
      studied. Seventy per cent of PI-IBS patients described sudden onset, 35% onset
      while travelling, 49.6% vomiting, 49.9% fever and 20.3% bloody diarrhoea.
      Compared to other IBS individuals, PI-IBS was significantly associated with
      living in Northern Europe and North America, having a hysterectomy, not having an
      appendicectomy, higher PHQ12-SS score and having more than one toilet in the
      family home. PI-IBS patients had more frequent stools. At one year recovery rate
      in the PI-IBS and non-PI-IBS group was 19.7% and 22.2%, p = 0.15. Recovery rates
      were lower for females (20.7%) vs males (38.8%), those with somatisation (23.0%)
      vs those without (33.2%) and those living in North America or Northern Europe
      (21.1%) vs living elsewhere (33.9%) p <= 0.001. Conclusion: PI-IBS accounts for
      around 13% of all IBS in this internet sample, with some distinctive features but
      a similar prognosis to the remainder.

PMID- 30288288
TI  - The patient burden of opioid-induced constipation: New insights from a large,
      multinational survey in five European countries.
AB  - Background: Despite its high prevalence, opioid-induced constipation (OIC)
      remains under-recognised and undertreated, and its true impact on wellbeing and
      quality of life (QoL) may be underestimated. Methods: A quantitative,
      questionnaire-based international survey was conducted. Results: Weak-opioid
      users appeared as bothered by constipation as strong-opioid users (38% vs 40%,
      respectively; p = 0.40), despite it causing less-severe physical symptoms and
      impact on QoL. Strong-opioid users meeting Rome IV OIC criteria appeared to
      experience greater symptomatic and biopsychosocial burden from constipation than
      those not satisfying these criteria. Almost one-fifth of respondents were
      dissatisfied with their current constipation treatment and around one-third found
      balancing the need for adequate pain relief with constipation side effects
      challenging. Consequently, more than half failed to adhere to their prescribed
      treatment regimens, or resorted to suboptimal strategies, e.g. 40% reduced their
      opioid intake, to relieve constipation. Almost 60% of healthcare professionals
      did not adequately counsel patients about constipation as a common side effect of
      opioid use. Conclusions: Findings suggest that both weak- and strong-opioid users
      suffer comparable bother and decreased QoL, Rome IV criteria can identify
      patients with more-severe OIC, but may underdiagnose patients showing fewer
      symptoms, and increased education is needed to manage patients' expectations and
      enable improved OIC self-management.

PMID- 30288290
TI  - Addendum to A study of dysphagia symptoms and esophageal body function in
      children undergoing anti-reflux surgery.

PMID- 30288289
TI  - Contribution of genetic amplification by PCR for the diagnosis of Helicobacter
      pylori infection in patients receiving proton pump inhibitors.
AB  - Background: Helicobacter pylori detection by standard methods may be altered by
      proton pump inhibitor (PPI) use. However, some patients cannot or should not
      interrupt PPI use before undergoing testing for H. pylori. Polymerase chain
      reaction (PCR) could allow more reliable H. pylori detection even in patients
      taking PPIs. Objective: The aim of our study is to compare the H. pylori
      infection diagnostic value of histological examination without and with
      immunohistochemical staining, bacterial culture and PCR, in PPI-treated vs
      untreated patients. Methods: Patients undergoing a gastric endoscopy for upper
      digestive symptoms were included. Gastric biopsy samples were obtained. The
      impact of taking PPI on the diagnostic performance of the different methods was
      studied. PCR results were confirmed by sequencing the glmM gene. Results: A total
      of 497 patients were included, of whom 192 were H. pylori positive. Fifty-two
      patients received PPIs during the 14 days preceding the endoscopy while 140 did
      not. All methods had lower sensitivity than PCR, in all cases (PPI treatment or
      not). PPI use did not change significantly the methods' sensitivities.
      Conclusion: The PCR method showed the best performance for the detection of H.
      pylori in gastric samples, whether or not patients received previous PPI
      treatment. This diagnosis test could become a new gold-standard test, especially
      in patients undergoing PPI treatment.

PMID- 30288291
TI  - United European Gastroenterology Research Prize Awardee 2018 - Cisca Wijmenga.

PMID- 30288292
TI  - Young GI angle: My biggest (career) mistake.

PMID- 30288293
TI  - A new anthropometric index for body fat estimation in patients with severe
      obesity.
AB  - Background: Body mass index (BMI) has been used to assess body adiposity, but it
      cannot adequately reflect body fat (BF) amount. The body adiposity index (BAI)
      has been shown a better performance than BMI for this purpose, but it can be
      inaccurate to estimate BF under extreme amounts of fat. Here, we propose a new
      anthropometric index, the Belarmino-Waitzberg (BeW) index, for specific
      estimation of BF in severely obese patients. Methods: In 144 adult patients with
      severe obesity, BF was estimated by air displacement plethysmography (ADP), as
      the reference method, along with the follow anthropometric measurements: height,
      abdominal circumference (AC), hip circumference (HC), weight, BMI (weight/
      height2) and BAI ([HC(cm) / height (m)1.5) - 18] * 100). Patients were
      proportionately distributed into two distinct databases, the building model
      database (BMD) and the validation model database (VMD), which were applied to
      develop and validate the BeW index, respectively. The BeW index was tested for
      gender and ethnicity adjustment as independent variables. The agreement of BF%
      values obtained by the new index and by BAI with ADP was also assessed. Results:
      The BF% was 52.05 +/- 5.42 for ADP and 59.11 +/- 5.95 for the BeW index (all
      results are expressed as the mean +/- standard deviation). A positive Pearson
      correlation (r = 0.74), a good accuracy (Cb = 0.94), and a positive Lin's
      concordance correlation (CCC = 0.70) were observed between the two groups. The
      95% limits of individual agreement between the BeW index and ADP were 6.8 to
      7.9%, compared to - 7.5 to 14.8% between the BAI and ADP. The new index, called
      the Belarmino-Waitzberg (BeW) index, showed an improvement of 2.1% for the R2
      value and a significant gender effect, therefore resulting in two different
      indexes for females and males, as follows: Female BeW = - 48.8 + 0.087 * AC(cm) +
      1.147 * HC(cm) - 0.003 * HC(cm)2 and Male BeW = - 48.8 + 0.087 * AC(cm) + 1.147 *
      HC(cm) - 0.003 * HC(cm)2-7.195. Conclusions: The new BeW index showed a good
      performance for BF estimation in patients with severe obesity and can be superior
      to the BAI for this purpose.

PMID- 30288294
TI  - Are There Differences in Workplace Accommodation Needs, Use and Unmet Needs Among
      Older Workers With Arthritis, Diabetes and No Chronic Conditions? Examining the
      Role of Health and Work Context.
AB  - The aging of workforces combined with the prevalence of age-related chronic
      diseases has generated interest in whether large numbers of older workers will
      need workplace accommodations. This research applied work functioning theory to
      examine accommodation availability, need and use in workers with arthritis,
      diabetes, or no chronic disabling diseases; factors associated with accommodation
      needs; and the relationship of accommodation needs met, unmet or exceeded to job
      outcomes. Participants were aged 50-67 years, employed, and had arthritis (n =
      631), diabetes (n = 286), both arthritis/diabetes (n = 111) or no chronic
      disabling conditions (healthy controls n = 538). They were recruited from a
      national panel of 80,000 individuals and a cross-sectional survey was
      administered online or by telephone. Questionnaires assessed demographics,
      health, work context, workplace accommodations, and job outcomes. Chi-square
      analyses, analyses of variance, and regression analyses compared groups.
      Respondents were similar in many demographic and work context factors. As
      expected, workers with arthritis and/or diabetes often reported poorer health and
      employment outcomes. Yet, there were few differences across health conditions in
      need for or use of accommodations with most participants reporting accommodations
      needs met. In keeping with work functioning theory, unmet accommodation needs
      were largely related to work context, not health. Workers whose accommodation
      needs were exceeded reported better job outcomes than those with accommodation
      needs met. Findings highlight both work context and health in understanding
      workplace accommodations and suggest that many older workers can meet
      accommodation needs with existing workplace practices. However, additional
      research aimed at workplace support and the timing of accommodation use is
      needed.

PMID- 30288295
TI  - Risk factors for venous irritation in patients receiving vinorelbine: a
      retrospective study.
AB  - Background: Vinorelbine is known to be effective in the treatment of non-small
      cell lung cancer and breast cancer. However, venous irritation is a common side
      effect. Although there have been some reports on risk factors for venous
      irritation in patients receiving vinorelbine, the factors evaluated have been
      limited and the results inconclusive. The aim of this study was to identify risk
      factors for venous irritation in patients receiving vinorelbine, and factors
      likely associated with venous irritation, including new factors such as hot
      compress with a hot towel  for prevention of venous irritation. Methods: We
      retrospectively reviewed patients treated with vinorelbine at Kyorin University
      Hospital, Japan, between March 2013 and December 2016 and divided them into the
      two groups according to whether or not they had venous irritation. Clinical
      characteristics were compared between the two groups. Results: Venous irritation
      occurred in 24 (38.1%) of 63 patients who received vinorelbine. The median number
      of times vinorelbine was administered before onset of venous irritation was 3
      (range 1-14). The group with venous irritation had a significantly lower body
      surface area than the group without venous irritation (p = 0.035). Low body
      surface area was also the only significant risk factor for vinorelbine-associated
      venous irritation in multivariate analysis (adjusted odds ratio 70.42 per 1
      m2decrement, 95% confidence interval 1.54-3236.25, p = 0.029). There was no
      association between the occurrence of venous irritation and the other covariates,
      such as use of a hot compress, history of diabetes mellitus, or use of a generic
      formulation of vinorelbine. Conclusion: Low body surface area may be a risk
      factor for venous irritation in patients receiving vinorelbine. Use of hot
      compress with a hot towel did not prevent venous irritation.

PMID- 30288296
TI  - Start-up financing of professional pest control in pig farming in North Rhine
      Westphalia in Germany.
AB  - Background: Due to the risk of spreading epizootic diseases through rodents, pest
      control is mandatory in pig farming in European countries. However, there is
      limited research focused on rodent control practices, usage of anticoagulant
      rodenticides, and the acceptance of Pest Control Operators (PCOs) in pig farming
      in Germany. Therefore, the present study aims to investigate current control
      practices in pig holdings and to analyze the potential of a financial support on
      the implementation of professional pest control. Results: Data were collected
      from monitoring records of PCOs and personal interviews with farmers and PCOs. 33
      of 47 farmers, who were offered the possibility to outsource rodent control to
      PCOs supported by financial contribution of the North Rhine-Westphalian Animal
      Disease Fund (TSK) for a period of 2 years, joined the project.Despite the
      widespread opinion that the professional would not be beneficial - the authors
      figured out that farmers could financially benefit in time saved and by improved
      rodent control measures from the work of the PCOs. Costs of pest control measures
      per operation on average did not differ significantly between costs incurred by
      employment of PCOs (1.310 ? per year) and calculated costs that arise by farmers
      themselves (1.217 ? per year).All PCOs used Difenacoum and Brodifacoum against
      pest infestations. In doing so, the infestation with rodents was reduced and most
      of the participating farmers assessed the project as successful and employ the
      PCOs permanently. However, mapping the farm locations to resistance areas of the
      Rodenticide Resistance Action Committee (RRAC) shows that Brodifacoum was
      frequently used in areas which are marked as areas that are at low risk or rather
      have no risk for resistance. The environmental risks, however, are increased in
      these areas. Conclusion: The instrument of temporal start-up financing
      professional pest control allows ensuring the continuous engagement of PCOs after
      the project period. This could possibly lead to long-term effects on the
      individual farm hygiene and on disease prevention. Nevertheless, important
      research questions with regard to the application of anticoagulant rodenticides
      of farmers and PCOs in livestock farming and with regard to risk mitigation
      measures were generated, meriting further investigation.

PMID- 30288297
TI  - Korea hypertension fact sheet 2018.
AB  - Background: The Korea Hypertension Fact Sheet 2018 aims to overview the magnitude
      and management status of hypertension, and their trends in Korea. Methods: The
      Hypertension Epidemiology Research Group analyzed the 1998-2016 Korea National
      Health and Nutrition Examination Survey data and the 2002-2016 Korea National
      Health Insurance Big Data. Results: The population average of systolic/diastolic
      blood pressure was 118/77 mmHg among Korean adults (age 30+) in 2016, showing
      little change in recent 10 years. However, the number of people with hypertension
      increased steadily, exceeding 11 million. The number of people diagnosed with
      hypertension increased from 3 million in 2002 to 8.9 million in 2016. The number
      of people using antihypertensive medication increased from 2.5 million in 2002 to
      8.2 million in 2016. However, only 5.7 million people are being treated
      constantly. Hypertension awareness, treatment, and control rates increased fast
      until 2007, but showed a plateau thereafter. More than half of the young
      hypertensive patients (30-49 years) did not know about and treat for their
      hypertension. Among patients prescribed antihypertensive medications, 45% was
      elderly people over the age of 65 years, 57% used anti-diabetic or cholesterol
      lowering medications, and 60% were prescribed two or more class of
      antihypertensive medications simultaneously. Conclusions: In Korea, the level of
      hypertension management has considerably improved over the last 20 years. In
      order to achieve further improvement in hypertension management status, we need
      to find the vulnerable subgroups and develop subgroup-specific intervention
      strategies. It is also becoming more important to manage hypertensive patients at
      older age and those with concurrent chronic diseases.

PMID- 30288298
TI  - How to engage patients in research and quality improvement in community-based
      primary care settings: protocol for a participatory action research pilot study.
AB  - Plain English summary: Making primary care clinics more patient-centered is key
      to improving patients' experience of care. If patients themselves were engaged in
      helping define priorities and suggesting quality improvements in the clinic, care
      would respond better to their needs. However, patient engagement is a new
      phenomenon, particularly in community based primary care clinics. How to engage
      patients in quality improvement in these clinics, or what effect this might have,
      is not well known. The involvement of patients needs to be adapted to the way
      these clinics function. The aim of this study is to create and evaluate a new
      model of patient engagement for quality improvement in community based primary
      care clinics. Patients, primary care professionals and researchers will create
      advisory councils in two primary care clinics in Quebec City (Canada). In each
      clinic, the advisory council will include 12 patients or caregivers registered at
      the clinic, a clinician and a clinic manager. The advisory council will meet
      every 6 weeks for a total of six meetings. Two patient-experts will facilitate
      meetings. During meetings, members of the council will list their needs in order
      of importance. Then they will suggest improvements in line with these needs. We
      will study if our advisory council model is well adapted to community based
      primary care settings and meets participants' expectations. At the end of the
      study we will be able to offer guidance about engaging patients with health
      professionals in quality improvement in primary care clinics. Abstract:
      Background Involvement of end-users, including patients, managers and clinicians,
      in identifying quality improvement and research priorities might improve the
      relevance of projects and increase their impact. Few patient engagement
      initiatives have taken place in community based primary care practices (CBPCPs)
      and best practices for engaging patients in such settings are not well defined.
      The aim of this pilot study is to develop and assess the feasibility of a new
      collaborative model of advisory council involving clinicians, managers, patients
      and caregivers in CBPCP to strengthen their capacity to conduct quality
      improvement and patient-oriented research projects. Methods We will conduct a
      participatory action research project in two non-academic CBPCPs in Quebec City
      (Canada). In each CBPCP, the advisory council will include 12 patients or
      caregivers, a clinician and a clinic manager. Patients or their caregivers will
      be identified by clinicians and contacted by patient-experts. They will be
      eligible if they are registered at the practice, motivated, and available to
      attend meetings. The council will meet every 6 weeks for a total of six meetings.
      Two patient-experts will guide council members to identify quality improvement
      priorities and patient-oriented research questions based on their experience in
      the clinic. They will then be supported to plan actions to target these
      priorities. Analysis of meetings will be based on feasibility criteria, notes by
      non-participant observers in log books, audio-recording of the meetings and
      questionnaires to evaluate council members' perceptions and the likelihood they
      would engage in such councils. Discussion The results of this study will  be a
      model of patient engagement and a discussion of factors to improve the model to
      fit the needs of primary care patients and professionals. This will lay the
      foundation for a sustainable structure for long-term patient engagement and
      contribute to the development of a patient-centered and quality-improvement
      culture in CBPCPs.

PMID- 30288301
TI  - CT and MRI findings of bronchopulmonary endometriosis: a case presentation.
AB  - Intrathoracic endometriosis is classified into pleurodiaphragmatic endometriosis
      and bronchopulmonary endometriosis. Bronchopulmonary endometriosis is rare.
      Computed tomography (CT) findings of bronchopulmonary endometriosis are lung
      nodules, with or without cavities, or surrounding ground-glass opacities.
      Features vary with menstrual status. Recently, the usefulness of magnetic
      resonance imaging (MRI) was reported for diagnosis of intrathoracic
      endometriosis, but most published reports were about pleurodiaphragmatic
      endometriosis. We present CT and MRI findings of bronchopulmonary endometriosis
      in the left lung that showed a gradually enlarging nodule with enhancing area.

PMID- 30288300
TI  - Beneficial coinfection can promote within-host viral diversity.
AB  - In many viral infections, a large number of different genetic variants can
      coexist within a host, leading to more virulent infections that are better able
      to evolve antiviral resistance and adapt to new hosts. But how is this diversity
      maintained? Why do faster-growing variants not outcompete slower-growing
      variants, and erode this diversity? One hypothesis is if there are mutually
      beneficial interactions between variants, with host cells infected by multiple
      different viral genomes producing more, or more effective, virions. We modelled
      this hypothesis with both mathematical models and simulations, and found that
      moderate levels of beneficial coinfection can maintain high levels of
      coexistence, even when coinfection is relatively rare, and when there are
      significant fitness differences between competing variants. Rare variants are
      more likely to be coinfecting with a different variant, and hence beneficial
      coinfection increases the relative fitness of rare variants through negative
      frequency dependence, and maintains diversity. We further find that coexisting
      variants sometimes reach unequal frequencies, depending on the extent to which
      different variants benefit from coinfection, and the ratio of variants which
      leads to the most productive infected cells. These factors could help drive the
      evolution of defective interfering particles, and help to explain why the
      different segments of multipartite viruses persist at different equilibrium
      frequencies.

PMID- 30288299
TI  - Islands of linkage in an ocean of pervasive recombination reveals two-speed
      evolution of human cytomegalovirus genomes.
AB  - Human cytomegalovirus (HCMV) infects most of the population worldwide, persisting
      throughout the host's life in a latent state with periodic episodes of
      reactivation. While typically asymptomatic, HCMV can cause fatal disease among
      congenitally infected infants and immunocompromised patients. These clinical
      issues are compounded by the emergence of antiviral resistance and the absence of
      an effective vaccine, the development of which is likely complicated by the
      numerous immune evasins encoded by HCMV to counter the host's adaptive immune
      responses, a feature that facilitates frequent super-infections. Understanding
      the evolutionary dynamics of HCMV is essential for the development of effective
      new drugs and vaccines. By comparing viral genomes from uncultivated or low
      passaged clinical samples of diverse origins, we observe evidence of frequent
      homologous recombination events, both recent and ancient, and no structure of
      HCMV genetic diversity at the whole-genome scale. Analysis of individual gene
      scale loci reveals a striking dichotomy: while most of the genome is highly
      conserved, recombines essentially freely and has evolved under purifying
      selection, 21 genes display extreme diversity, structured into distinct genotypes
      that do not recombine with each other. Most of these hyper-variable genes encode
      glycoproteins involved in cell entry or escape of host immunity. Evidence that
      half of them have diverged through episodes of intense positive selection
      suggests that rapid evolution of hyper-variable loci is likely driven by
      interactions with host immunity. It appears that this process is enabled by
      recombination unlinking hyper-variable loci from strongly constrained neighboring
      sites. It is conceivable that viral mechanisms facilitating super-infection have
      evolved to promote recombination between diverged genotypes, allowing the virus
      to continuously diversify at key loci to escape immune detection, while
      maintaining a genome optimally adapted to its asymptomatic infectious lifecycle.

PMID- 30288302
TI  - Editor-in-Chief's welcome to Hepatology, Medicine and Policy.
AB  - Hepatology, Medicine and Policy (HMAP), a new open-access peer-reviewed journal,
      is making its debut at a time when the hepatitis field is seeing great progress
      but still has far to go. The World Health Organization and many countries have
      shown increasing interest in viral hepatitis in recent years, helping to foster a
      stronger response to this group of diseases. Meanwhile, alcohol-associated
      cirrhosis and alcohol-associated liver cancer continue to take a heavy toll
      worldwide, as does non-alcoholic fatty liver disease. The lack of a unified
      strategic response to viral hepatitis and other liver diseases is the impetus for
      launching HMAP, which will publish policy, public health and social science
      articles alongside clinical science articles. It will encourage submissions in
      diverse domains such as disease prevention and management, epidemiology,
      economics, health behavior, health service delivery, ethics, human rights, and
      the role of laws, policies and clinical guidelines in shaping health initiatives.
      The current attention to powerful new hepatitis C treatments presents a strategic
      opportunity to more comprehensively address the full constellation of biomedical
      and social issues relating to liver health. HMAP is committed to publishing
      research and policy articles that help to drive forward this broader agenda.

PMID- 30288303
TI  - Predisposing, enabling, and need factors associated with utilization of HCV
      testing services among PWID in two settings in India.
AB  - Background: The Hepatitis C virus (HCV) is very common among people who inject
      drugs (PWID), yet PWID in India have suboptimal access to HCV testing and
      treatment. This study sought to identify HCV risk factors among male PWID who
      utilized a free needle and syringe exchange program and to examine the
      predisposing, enabling, and need factors associated with utilization of HCV
      testing services by those PWID reporting that they had been tested. Methods: A
      cross-sectional study was conducted in Imphal, Manipur and Amritsar, Punjab.
      These two settings have high HCV prevalence and large numbers of PWID. A team of
      18 field investigators obtained data through face-to-face interviews using a
      structured multiple-choice questionnaire. The questionnaire was administered to
      1241 of 2644 male PWID aged 15 years and above enrolled in the needle and syringe
      program of India's AIDS Control Program, with study participants selected through
      consecutive sampling. Statistical analyses included descriptive statistics and
      multivariate regression. Results: Twenty-four percent of PWID in our study sample
      reported having been tested for HCV. Unlike PWID in Imphal, more than half of
      PWID in Amritsar reported unprotected sex and use of alcohol or non-injecting
      drugs as being among their HCV risk factors (67.1 and 77.8 %, respectively).
      However, opioid substitution therapy non-adherence was reported more often in
      Imphal than in Amritsar. Education, marital status, place of residence and
      duration of injecting drug use were found to significantly enable access to HCV
      testing while alcohol use, frequent mobility and unprotected sex were found to
      significantly inhibit access to HCV testing for PWID after controlling for other
      explanatory variables. Conclusions: Predisposing and enabling determinants
      provide an area for developing effective interventions to improve HCV testing
      practices among PWID. HCV prevention programs that address safe injecting and
      sexual practices, OST adherence and frequent mobility customized for PWID by age
      are strongly recommended.

PMID- 30288304
TI  - A new paradigm evaluating cost per cure of HCV infection in the UK.
AB  - Background: New interferon (IFN)-free treatments for hepatitis C are more
      effective, safer but more expensive than current IFN-based therapies. Comparative
      data of these, versus current first generation protease inhibitors (PI) with
      regard to costs and treatment outcomes are needed. We investigated the real-world
      effectiveness, safety and cost per cure of 1st generation PI-based therapies in
      the UK. Methods: Medical records review of patients within the HCV Research UK
      database. Patients had received treatment with telaprevir or boceprevir and
      pegylated interferon and ribavirin (PR). Data on treatment outcome, healthcare
      utilisation and adverse events (AEs) requiring intervention were collected and
      analysed overall and by subgroups. Costs of visits, tests, therapies, adverse
      events and hospitalisations were estimated at the patient level. Total cost per
      cure was calculated as total median cost divided by SVR rate. Results: 154
      patients from 35 centres were analysed. Overall median total cost per cure was
      L44,852 (subgroup range,: L35,492 to L107,288). Total treatment costs were
      accounted for by PI: 68.3 %, PR: 26.3 %, AE management: 5.4 %. Overall SVR was
      62.3 % (range 25 % to 86.2 %). 36 % of patients experienced treatment-related AEs
      requiring intervention, 10 % required treatment-related hospitalisation.
      Conclusions: This is the first UK multicentre study of outcomes and costs of PI
      based HCV treatments in clinical practice. There was substantial variation in
      total cost per cure among patient subgroups and high rates of treatment-related
      discontinuations, AEs and hospitalisations. Real world safety, effectiveness and
      total cost per cure for the new IFN free combinations should be compared against
      this baseline.

PMID- 30288305
TI  - Urgent action to fight hepatitis C in people who inject drugs in Europe.
AB  - Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and liver
      cancer, is curable in most people. Injecting drug use currently accounts for 80 %
      of new HCV infections with a known transmission route in the European Union (EU).
      HCV has generally received little attention from the public or policymakers in
      the EU, with major gaps in national-level strategies, action plans, guidelines
      and the evidence base. Specifically, people who inject drugs (PWID) are often
      excluded from treatment owing to various patient, healthcare provider and health
      system factors. All policymakers responsible for health services in EU countries
      should ensure that prevention, treatment, care and support interventions
      addressing HCV in PWID are developed and implemented. According to current best
      practice, PWID should have access to comprehensive, evidence-based
      multiprofessional harm reduction (especially opioid substitution therapy and
      clean needles and syringes) and support/care services based in the community and
      modified with community involvement to accommodate this hard-to-reach population.
      Other recommended components of care include vaccination against hepatitis B and
      other infections; peer support interventions; HIV testing, prevention and
      treatment; drug and alcohol services; psychological care as needed; and social
      support services. HCV testing should be performed regularly in PWID to identify
      infected persons and engage them in care. HCV-infected PWID should be considered
      for antiviral treatment (based on an individualised assessment and delivered
      within multidisciplinary care/support programmes) both to cure infected
      individuals and prevent onward transmission. Modelling data suggest that the HCV
      disease burden can only be cut substantially if antiviral treatment is scaled up
      together with prevention programmes. Measures should be taken to reduce stigma
      and discrimination against PWID at the provider and institutional levels. In
      conclusion, strategic action at the policy level is urgently needed to increase
      access to HCV prevention, testing and treatment among PWID, the group at highest
      risk of HCV infection. Such action has the potential to substantially reduce the
      number of infected persons, along with the disease burden and related care costs.

PMID- 30288306
TI  - State of viral hepatitis knowledge and testing uptake in Brazil: Findings from
      the National Survey of Knowledge, Attitudes and Practices (PCAP-2013).
AB  - Background: Data were obtained from the third National Survey of Knowledge,
      Attitudes and Practices of HIV and other Sexually Transmitted Infections (STI)
      (PCAP-2013) and used to describe the current state of viral hepatitis (VH)
      knowledge and screening as well as the prevalence of viral hepatitis B (HBV)
      vaccination in Brazil and to assess the factors associated with testing uptake.
      Methods: A probability sample survey of 12,000 individuals (50 % men) aged
      between 15 and 64 years was conducted between October and December of 2013. The
      participants completed the survey in their own homes through computer-assisted
      face-to-face interviews and self-interviews. We analysed data related to self
      reported knowledge of VH routes and screening uptake after weighting the
      variables to account for unequal selection probabilities and correct for
      differences in sex, age and region according to 2010 census figures. Results: The
      levels of correct knowledge regarding HBV and HCV transmission through
      unprotected sex were 33.1 and 34.3 %, respectively. The levels of correct
      knowledge regarding HBV and HCV transmission through tattooing/piercing were 26.4
      and 24.5 %, respectively. Overall, 29 % of the respondents reported having
      underwent VH screening and 73.9 % reported prior HBV vaccination. VH screening
      was associated with the following factors: age between 25 and 49 years (adjusted
      male odds ratio (OR): 2.29, [95 % confidence interval (CI): 1.83-2.87]; female
      OR: 1.36, [95 % CI: 1.10-1.67]); age between 50 and 64 years (male OR: 1.52, [CI:
      1.13-2.03]; female OR: 1.29, [CI: 1.02-1.63]); initial sexual intercourse before
      the age of 15 years in men (OR: 1.32, [CI: 1.10-1.57]); higher socioeconomic
      statuses of group A (male OR: 2.38, [CI: 1.81-3.13]; female OR: 2.10, [CI: 1.66
      2.68]) and B (female OR: 1.56, [CI: 1.27-1.93]); and having ever been tested for
      HIV (male OR: 7.50, [CI: 5.82-8.53]; female OR: 7.13, [CI: 5.97-8.54]).
      Conclusions: This study revealed low levels of knowledge regarding VH
      transmission and screening practices in the general Brazilian population,
      especially among younger individuals and those with lower socioeconomic status.
      Efforts to enhance awareness campaigns and expand testing sites are needed to
      remove barriers to testing.

PMID- 30288307
TI  - Strengthening hepatitis B and C surveillance in Europe: results from the two
      global hepatitis policy surveys (2013 and 2014).
AB  - Background: Hepatitis B and C are major public health threats in the World Health
      Organization (WHO) European Region. Viral hepatitis surveillance shortcomings
      have resulted in many WHO Member States having insufficient data available to
      guide decision-making. This study describes surveillance in the region based on a
      quantitative sub-analysis of findings from the 2013 WHO viral hepatitis policy
      report and a qualitative analysis of civil society survey responses associated
      with these findings. Methods: Descriptive statistics were created from
      information that national government focal points for viral hepatitis in 44
      countries had previously reported in response to the WHO survey. Bivariate
      analysis was performed to compare data from within and outside of the European
      Union/European Economic Area (EU/EEA). Survey responses from civil society
      organizations in the countries of the WHO European Region were collated, and a
      descriptive analysis of the comments on surveillance-related questions was
      performed to identify key themes. Results: The response rate for the survey of
      governments was 83 % among both EU/EEA countries (25/30) and non-EU/EEA countries
      (19/23). More than 90 % of governments reported having national surveillance
      systems for the acute forms of hepatitis B and hepatitis C, but less than two
      thirds reported surveillance for the chronic forms of both diseases. High
      proportions of governments reported having central registries for the reporting
      of deaths (96 %) and liver cancer cases (80 %), while less than half reported
      regularly conducting viral hepatitis sero-surveys. All responding Member States
      reported having adequate laboratory capacity nationally to support hepatitis
      outbreak investigations and other surveillance activities. Target populations for
      sero-surveys most commonly included people who inject drugs (27 %), the general
      population (25 %), men who have sex with men (20 %) and pregnant women (20 %).
      Few statistically significant differences were found between EU/EEA and non
      EU/EEA countries. Conclusions: Study findings indicated a capacity for robust
      viral hepatitis surveillance across the WHO European Region, with most countries
      having important surveillance components in place, but notable weaknesses were
      also identified. There is an urgent need for countries throughout the region to
      strengthen their surveillance programs in order to maximize the population-level
      impact of advances in HBV and HCV prevention and treatment.

PMID- 30288308
TI  - Hepatitis B knowledge among key stakeholders in Haimen City, China: Implications
      for addressing chronic HBV infection.
AB  - Background: This article describes hepatitis B-related knowledge, attitudes and
      practices after completion of the Gateway to Care campaign, a citywide public
      health education program that targeted city residents, health care providers and
      individuals chronically infected with hepatitis B virus in Haimen City, China.
      Methods: Pre/post questionnaires assessed hepatitis B knowledge change among
      health care providers and post-campaign surveys evaluated hepatitis B knowledge,
      attitudes and behaviors (including stigma-related beliefs and practices) among
      health care providers, city residents and chronically infected individuals. Focus
      groups were conducted to gain a more in-depth understanding of the needs of the
      target communities, and to identify future intervention strategies to improve
      hepatitis B testing and linkage to care and treatment. Results: Results indicate
      high levels of hepatitis B knowledge among multiple stakeholders in Haimen City,
      with significant knowledge improvement among health care providers. Stigma
      related beliefs and myths regarding separation of infected individuals from
      certain aspects of family life were common among all stakeholder groups, despite
      high levels of accurate knowledge about hepatitis B transmission and prevention.
      Self-report of hepatitis B screening was low among city residents, as was
      awareness of hepatitis B treatment. Conclusions: More efforts are needed to
      improve awareness of HBV treatment, decrease HBV-related stigma, improve
      screening rates, and reduce cost of antiviral treatment. Future interventions in
      Haimen City should be driven by behavioral change theory, to not only improve
      knowledge, but to improve screening behaviors and address hepatitis B-related
      stigma and discrimination.

PMID- 30288309
TI  - Hepatitis B knowledge among women of childbearing age in three slums in Mumbai: a
      cross-sectional survey.
AB  - Background: More than 17 million people in India are chronically infected with
      the hepatitis B virus (HBV). Approximately one million of the 26 million children
      born in India annually will develop chronic HBV infection in the course of their
      lives. Studies have put the HBsAg prevalence rate among pregnant women in India
      between 0.9 % and 3.1, indicating a considerable need for public health
      interventions aimed at protecting their offspring from infection. The PAHAL
      project in Mumbai, India, conducted an HBV knowledge survey among women of
      childbearing age in three local slum communities preparatory to planning a
      comprehensive HBV education intervention targeting this population. Methods:
      Female health workers approached all households in three designated slum
      neighborhoods: one each in the eastern suburbs (ES), western suburbs (WS) and
      Island City (IC). Female residents aged 18-45 were invited to participate in the
      study, and those who agreed to participate responded to a questionnaire that was
      administered in the form of an oral interview. The five sections of the
      questionnaire addressed demography, hepatitis B knowledge, personal risk related
      to hepatitis B, pregnancy and childbearing history, and the participant's most
      recent pregnancy. A descriptive statistical analysis was performed. Results:
      Health workers submitted 6571 interview forms that were suitable for analysis
      (ES, 28 %; WS, 34 %; IC, 38 %). Large proportions of study participants were
      married (89 %), were not employed (94 %) and had completed less than 12 years of
      school (87 %). Only 240 (3.6 %) women answered yes when asked if they knew about
      hepatitis B. Among those women, there were high levels of accurate knowledge
      regarding some modes of hepatitis B transmission but low levels of accurate
      knowledge regarding other modes. Twenty-two percent of 739 women who had given
      birth within the previous 36 months reported that they had been tested for HBV
      during pregnancy. While 70 % of these women reported that their children had
      received three doses of hepatitis B vaccine, reported vaccination levels varied
      greatly across the three study areas. Conclusions: Despite the availability of a
      safe HBV vaccine, which is free for newborns and infants in many parts of India,
      preventing mother-to-child transmission of HBV remains a major challenge. Low
      awareness of HBV among women of childbearing age in Mumbai-area slums indicates a
      need for educational interventions targeting this population.

PMID- 30288310
TI  - A community- based hepatitis B linkage-to-care program: a case study on Asian
      Americans chronically infected with hepatitis B virus.
AB  - Background: Hepatitis B is an important disease of ethnic disparity which affects
      Asian Americans and other minority populations disproportionately. Despite the
      high prevalence of hepatitis B in Asian Americans, many of them remain unscreened
      and untreated. A majority of the individuals chronically infected with hepatitis
      B virus (HBV) are not linked to care, for instance, due to a lack of culturally
      competent programs. There are many serious barriers preventing linkage to care
      (LTC), including personal, socio-cultural, and economic issues. The purpose of
      this study was to evaluate various barriers affecting LTC and to investigate the
      role and efficacy of a community-based Patient Navigator (PN) program in
      expediting LTC and in improving health outcomes for hepatitis B patients in a
      high risk population. Methods: A total of 45 individuals chronically infected
      with HBV were identified through community screening events and were subsequently
      linked to patient navigators (PN), who then arranged for the patients to have a
      medical evaluation with a provider of their choice in their communities. The
      navigators kept detailed records of the patients' progress towards goal, and
      planned follow up visits for each patient. A self-report questionnaire was
      employed to assess patients' demographics, history of HBV infection, and barriers
      in accessing health care. Specifically, the levels of importance of the barriers
      due to language, culture, financial reasons were assessed. Results: The study
      revealed that 38 of the 45 HBV infected individuals knew about their infection
      status from previous screening. Forty two out of 45 HBV infected individuals were
      linked to care within a 12 month period, demonstrating a high linkage rate. Most
      significant barriers identified were language and finance, followed by cultural
      barrier and others. Conclusion: There are specific barriers to accessing adequate
      care for the patients affected by chronic hepatitis B (CHB) in Korean American
      community. The implementation of a PN program in conjunction with the community
      network of health care providers may help to overcome the barriers and facilitate
      LTC in hepatitis B.

PMID- 30288311
TI  - Coverage of different health insurance programs and medical costs associated with
      chronic hepatitis C infection in mainland China: a cross-sectional survey in 20
      provinces.
AB  - Background: Hepatitis C virus (HCV) imposes a considerable disease burden in
      China, with at least 10 million people chronically infected. Little is known
      about the financial impact of the HCV epidemic, nor about the extent to which
      various forms of insurance are providing HCV patients with financial protection.
      A cross-sectional multi-site study was conducted to acquire data that will aid
      policy-makers and other stakeholders in developing effective strategies to
      address this situation. Methods: At 29 hospitals across China, inpatients and
      outpatients with chronic HCV were surveyed about their insurance coverage and
      medical costs. Percentages, means and medians were calculated, and differences in
      continuous variables among multiple groups were analyzed using the Kruskal-Wallis
      test or Wilcoxon two-sample test. Results: Many inpatients (N = 593) and
      outpatients (N = 523) reported being covered by one of three major types of
      government health insurance, but 13 % of inpatients and 43 % of outpatients
      reported having no insurance. Among inpatients, the total median cost per
      hospitalization per patient was 8212 Renminbi (RMB). The category of expenditure
      with the highest median cost per hospitalization was Western medicine, followed
      by lab tests and Chinese medicine. The median cost per hospitalization was far
      higher for patients who had hepatocellular carcinoma than for those with less
      severe forms of liver disease. Outpatient antiviral therapy costs ranged from a
      median of 377 RMB for ribavirin to a median of 37,400 RMB for pegylated
      interferon-alpha for up to one year of treatment. Conclusions: For uninsured
      chronic HCV patients in China, inpatient and outpatient costs may be financially
      devastating. Research is needed on how different approaches to financing HCV
      treatment and care might improve health outcomes as well as achieve cost savings
      by enabling more people to be cured of HCV.

PMID- 30288312
TI  - Concordance between self-reported and measured HIV and hepatitis C virus
      infection status among people who inject drugs in Germany.
AB  - Background: People who inject drugs (PWID) are disproportionately affected by
      both HIV and hepatitis C infection (HCV). Awareness of infection status is
      essential to ensure linkage to appropriate healthcare for those infected, who
      need treatment and regular follow-up, as well as for uninfected individuals, who
      need access to targeted testing and counselling services. In this paper we
      compare self-reported HIV and HCV status with serological markers of infection
      among PWID recruited through respondent driven sampling. Methods: From 2011
      through 2014, biological and behavioural data was collected from 2,077 PWID in
      Germany. Dried blood spots from capillary blood samples were collected and
      screened for HCV antibodies, HCV RNA and HIV-1/-2 antibodies. HIV reactive
      samples were confirmed by Western blot. Results: Laboratory testing revealed that
      5 % were infected with HIV and 81 % were aware of being infected. Chronic HCV
      infection was detected in 41 % of the participants, 2 % had an acute HCV
      infection, 22 % had a cleared infection, and 34 % were unexposed to HCV. The
      concordance between self-reported and measured HCV status was lower than for HIV,
      with 73 % of those with chronic HCV infection being aware of their infection.
      Conclusions: We found a relatively high awareness of HIV and HCV infection status
      among PWID. Nevertheless, access to appropriate testing, counselling and care
      services targeted to the needs of PWID should be further improved, particularly
      concerning HCV. Trial registration: Ethical approval was received from the ethics
      committee at the medical university of Charite, Berlin, Germany in May 2011 and
      with an amendment approved retrospectively on 19/11/2012 (No EA4/036/11). The
      German Federal Commissioner for Data Protection and Freedom of Information
      approved the study protocol retrospectively on 29/11/2012 (III-401/008#0035).

PMID- 30288315
TI  - The hurdle with remaining risk for hepatocellular carcinoma in cirrhotic patients
      after a hepatitis C cure.
AB  - After introduction of new direct acting antivirals (DAAs) against hepatitis C,
      the cure rate has increased substantially especially in patients with liver
      cirrhosis. Decreased but remaining risk for hepatocellular carcinoma (HCC) has
      been shown in patients with liver cirrhosis after cure, in previous studies with
      interferon (IFN)-based treatments. This risk for HCCs is expected to become the
      next hurdle in the management of hepatitis C patients, as the number of treated
      and cured patients with liver cirrhosis is increasing dramatically. At the recent
      International Liver Congress 2016, Barcelona, Spain, a potentially alarming
      report was presented by Buonfiglioli F et al., among otherwise positive reports,
      for patients with prior HCC being treated with DAAs. This preliminary report
      showed a high early recurrence rate of 29 % for HCC after initiation of DAA
      treatment in patients with treated HCC, at follow-ups 12-24 weeks post-treatment.
      Another study was published just prior to this report by Reig M et al. showing
      similarly high recurrence rate for HCC. In this study, patients who have been
      treated for HCC with ablation, resection or transarterial chemoembolization, and
      no sign of remaining HCC at treatment start, were analysed for the risk of HCC
      recurrence after DAA treatment initiation. After a median follow-up time of 5.7
      months, recurrence rate of HCC was seen in 28 %. The disadvantage of these
      studies was the lack of any control group, but these figures were unexpectedly
      high compared to figures in previous studies. These findings need to be further
      explored and eventually confirmed in other studies before making any firm
      conclusions and change of the routine practice. Until we have more data, the
      eventual risks for early HCC recurrence and other risks must be weighed against
      other benefits of these DAAs, halting liver disease progression, on an individual
      basis.

PMID- 30288314
TI  - Antiretroviral therapy and liver disease progression in HIV and hepatitis C co
      infected patients: a systematic review and meta-analysis.
AB  - Background: HIV co-infection exacerbates hepatitis C disease, increasing the risk
      of cirrhosis and hepatitis C-related mortality. Combination antiretroviral
      therapy (cART) is the current standard treatment for co-infected individuals, but
      the impact of cART and antiretroviral (ARV) monotherapy on liver disease in this
      population is unclear. We aimed to assess the effect of cART and ARV monotherapy
      on liver disease progression and liver-related mortality in individuals co
      infected with HIV and chronic hepatitis C. Methods: A systematic review with meta
      analyses was conducted. MEDLINE and EMBASE bibliographic databases were searched
      up to September 2015. Study quality was assessed using a modified Newcastle
      Ottawa scale. Results were synthesised narratively and by meta-analysis. Results:
      Fourteen observational studies were included. In analyses that adjusted for
      potential confounders, risk of liver-related mortality was significantly lower in
      patients receiving cART (hazard ratio/odds ratio 0.31, 95 % CI 0.14 to 0.70).
      Results were similar in unadjusted analyses (relative risk 0.40, 95 % CI 0.29 to
      0.55). For outcomes where meta-analysis could not be performed, results were less
      consistent. Some studies found cART was associated with lower incidence of, or
      slower progression of liver disease, fibrosis and cirrhosis, while others showed
      no evidence of benefit. We found no evidence of liver-related harm from cART or
      ARV monotherapy compared with no HIV therapy. Conclusions: cART was associated
      with significantly lower liver-related mortality in patients co-infected with HIV
      and HCV. Evidence of a positive association between cART and/or ARV monotherapy
      and liver-disease progression was less clear, but there was no evidence to
      suggest that the absence of antiretroviral therapy was preferable.

PMID- 30288316
TI  - Roundtable discussion: how the World Hepatitis Summit 2015 strengthened
      stakeholders' efforts to combat viral hepatitis.
AB  - The inaugural World Hepatitis Summit was jointly convened by the World Health
      Organization (WHO) and the World Hepatitis Alliance and hosted by the Scottish
      Government and supported by Glasgow Caledonian University and Health Protection
      Scotland in September 2015. The three day event convened a broad range of
      stakeholders to meet and share ideas, experience and best practice in addressing
      the many facets of viral hepatitis prevention, diagnosis and treatment. With the
      next World Hepatitis Summit scheduled to take place from 1 to 3 November 2017,
      the World Hepatitis Alliance asked Hepatology, Medicine and Policy to commission
      a roundtable discussion article in order to encourage reflection on how the 2015
      Summit was significant for stakeholders' efforts and why it is important to keep
      the momentum going ahead of the World Hepatitis Summit 2017 and in the light of
      the newly adopted first-ever Global Health Sector Strategy on Viral Hepatitis.

PMID- 30288317
TI  - The Berlin Hepatitis C Manifesto: access to prevention, testing, treatment and
      care for people who use drugs.
AB  - The treatment of hepatitis C has entered a new era since the advent of curative
      pharmaceuticals. As policy, government and civil society assemble in response,
      there are still gaps to be addressed. The Manifesto on Hepatitis C and Drug Use,
      launched in Berlin during the Correlation Hepatitis C Initiative conference in
      October 2014, was formulated and endorsed by many key organizations in the
      hepatitis field. The Manifesto takes strides to pinpoint shortcomings in
      hepatitis action oriented towards the population most affected by the hepatitis C
      virus (HCV): active drug users. Despite a considerable amount of evidence that
      active drug users are disproportionately affected by HCV, barriers to care
      remain. Engagement with representatives of communities of people who inject drugs
      (PWID) is imperative in order to effectively create guidelines which reflect
      reality. Unfortunately, widespread systemic stigmatization and lack of trust
      between affected communities, decision-makers and healthcare professionals have
      reproduced this divide. The Berlin Manifesto has identified a disconnect between
      evidence and action which must be answered. In this roundtable discussion,
      experts from diverse parts of the hepatitis community have contributed their
      perspectives and experience on access to prevention, testing, and treatment for
      HCV in PWID. The authors discuss relevant topics such as realities of access to
      HCV treatment in the United Kingdom, interventions of a regional network of
      active drug users in Europe and lack of PWID involvement in government policy in
      Catalonia. Collectively they challenge the neglect of HCV in PWID by many
      decision-makers and health care professionals and promote a scale-up of
      integrated prevention and treatment strategies focusing on this population. The
      authors' conclusions aim to clarify the discourse on hepatitis in order to
      prevent disease, save lives and work towards eventual hepatitis elimination.

PMID- 30288318
TI  - Responding to HBV and HCV in China and India: thematic series introduction.

PMID- 30288313
TI  - HCV/HIV coinfection among people who inject drugs and enter opioid substitution
      treatment in Greece: prevalence and correlates.
AB  - Background: HCV/HIV coinfection in people who inject drugs is a public health
      issue, which presents a variety of challenges to healthcare providers. The
      determinants of HCV/HIV coinfection in this population are nonetheless not well
      known. The aim of the present study is to identify the factors associated with
      HCV/HIV coinfection in people who inject drugs and enter drug-related treatment.
      Methods: Linked serological and behavioral data were collected from people who
      entered 38 opioid substitution treatment clinics in central and southern Greece
      between January and December 2013. Three mutually exclusive groups were defined
      based on the presence of HCV and HIV antibodies. Group 1 clients had neither
      infection, Group 2 had HCV but not HIV, and Group 3 had HCV/HIV coinfection.
      Multinomial logistic regression analyses identified differences between groups
      according to socio-demographic, drug use and higher-risk behavioral
      characteristics. Results: Our study population consisted of 580 people who
      injected drugs in the past 12 months (79.8 % males, with median age 36
      years).79.4 % were HCV and 15.7 % HIV infected. Of those with complete
      serological data in both HCV and HIV indicators, 20.4 % were uninfected, 64.0 %
      HCV monoinfected, and 14.9 % HCV/HIV coinfected. HCV infection with or without
      HIV coinfection was positively associated with living alone or with a
      spouse/partner without children, prior incarceration, drug injecting histories of
      >=10 years, and syringe sharing in the past 12 months, and negatively associated
      with never having previously been tested for HCV. HCV/HIV coinfection, but not
      HCV infection alone, was positively associated with residence in urban areas
      (relative risk ratio [RRR] = 4.8, 95 % confidence interval [CI]: 1.7-13.7, p =
      0.004) and averaging >3 injections a day in the past 30 days (RRR = 4.5, 95 % CI:
      1.6-12.8, p = 0.005), and negatively associated with using a condom in the last
      sexual intercourse. Conclusions: People who inject drugs and live in urban areas
      and inject frequently have higher risk of coinfection. Findings highlight the
      need for scaling-up needle and syringe programs in inner city areas and promoting
      access of this population to screening and treatment, especially in prisons. The
      protective role of living with parents and children could inform the
      implementation of indicated interventions.

PMID- 30288319
TI  - Innovative sources for funding of viral hepatitis prevention and treatment in low
      and middle-income countries: a roundtable meeting report.
AB  - Hepatitis B is preventable and hepatitis C is treatable even if still at a high
      cost; most people who are infected with hepatitis B or C virus have not been
      screened yet and are unaware of their infections; and most countries, especially
      developing countries, do not have a national plan to prevent and control viral
      hepatitis. The advent of effective new treatments for hepatitis C has been an
      agent of change, allowing consideration of the feasibility of eliminating that
      disease and accelerating the control of viral hepatitis generally. These facts
      inspired the Viral Hepatitis Prevention Board (VHPB) to organize a meeting in
      London (8-9 June 2015) on innovative sources for funding of viral hepatitis
      prevention and treatment in low- and middle-income countries. The main focus of
      the meeting was to provide an overview of current health systems controlling
      viral hepatitis in low- and middle-income countries (LMICs); to identify ways to
      increase political commitment and financial sustainability of viral hepatitis
      prevention and control programmes in such countries; to identify potential
      funders and explore new funding mechanisms; to discuss lessons learnt about
      funding other disease programmes; to investigate how to convince and motivate
      decision-makers to fund viral hepatitis programmes in LMICs; to provide options
      for improving access to affordable screening and treatment of viral hepatitis in
      LMICs; and to list the commitments required for funding by donors, including
      governments, bilateral and multilateral organizations, non-traditional donors,
      development banks, foundations, and commercial financial institutions. To improve
      viral hepatitis prevention and treatment in LMICs participating hepatitis and
      financing experts identified the most urgent needs. Data on burden of disease
      must be improved. Comprehensive hepatitis policies and strategies should be
      drafted and implemented, and existing strategies and policies improved to
      increase access to treatment and prevention. Strong political will and leadership
      should be generated, potential partners identified and partnerships created.
      Potential funders and funding mechanisms have to be researched. The outcome of
      this meeting was integrated in a VHPB project to investigate creative financing
      solutions to expand access to and provision of screening and other preventive
      services, treatment and care of hepatitis B and C in LMICs. The report is
      available on www.vhpb.org.

PMID- 30288320
TI  - Incidence of hepatitis C among people who inject drugs in Ireland.
AB  - Background: Comprehensive information on the incidence and duration of hepatitis
      C virus (HCV) infection for people who inject drugs (PWID) in Ireland is not
      available. We created an incidence curve of injecting drug use in Ireland and
      subsequently estimated incidence of hepatitis C virus (HCV) infection. Methods:
      Anonymised data from the National Drug Treatment Reporting System (NDTRS) were
      used to identify all people who inject drugs (PWIDs) and who entered drug
      treatment for the first time between 1991 and 2014. A curve, estimating the
      incidence of injecting, was created to plot PWIDs by year of commencing
      injecting. The curve was adjusted for missing data on PWIDs in treatment and for
      PWIDs who were never treated. An adjustment was made to account for injectors who
      had never shared injecting equipment. The incidence of HCV infection and chronic
      infection in PWIDs was estimated by applying published rates. Results: Between
      1991 and 2014, 14,320 injectors were registered on NDTRS. The majority were young
      (median age 25 years), male (74%), lived in Dublin (73%) and injected an opiate
      (e.g. heroin) (94%). The estimated total number of injectors up to the end of
      2014 was 16,382. An estimated 12,423 (95% CI 10,799-13,161) were infected with
      HCV, and 9,317 (95% CI 8,022-9,996) became chronically infected. The estimated
      annual number of new HCV infections among PWIDs increased steeply from the late
      1970s and peaked in 1998. By 2014, almost 30% of injectors were estimated to have
      been infected for over 20 years. Conclusions: This is the first comprehensive
      national estimate of the incidence of HCV in PWIDs in Ireland and will inform
      planning and developing appropriate health care services.

PMID- 30288321
TI  - Highlights from the 3rd international HIV/viral hepatitis Co-infection meeting -
      HIV/viral hepatitis: improving diagnosis, antiviral therapy and access.
AB  - The International AIDS Society convened the 3rd International HIV/Viral Hepatitis
      Co-Infection Meeting on 17 July 2016 as part of the pre-conference program
      preceding the 21st International AIDS Conference held in Durban, South Africa.
      The meeting brought together a diversity of scientific, technical and community
      interests to discuss opportunities and challenges for increased prevention,
      diagnosis and treatment of viral hepatitis in people living with HIV,
      particularly in low- and middle-income settings. The objectives of the meeting
      were:i.To review the latest therapeutic developments in viral hepatitis;ii.To
      identify challenges such as high cost of medications for hepatitis C virus (HCV)
      and risk of developing viral resistance, and successes, such as the provision of
      HCV treatment in community-based settings, movements to reduce drug costs and
      increasing access, in relation to scaling up diagnosis, screening, antiviral
      treatment and prevention of viral hepatitis;iii.To advance the agenda for
      elimination of viral hepatitis as a public health problem. Discussions centred
      around the six key interventions outlined by the World Health Organization Global
      Health Sector Strategy on Viral Hepatitis 2016-2021: hepatitis B virus (HBV)
      vaccination (including birth dose); safe injection practices plus safe blood;
      harm reduction among people who inject drugs; safer sex practices; hepatitis B
      treatment; and hepatitis C cure. This article summarizes the main issues and
      findings discussed during the pre-conference meeting. One of the recommendations
      from the meeting delegates is universal implementation of birth dose vaccination
      for HBV without further delay to prevent mother-to-child transmission of
      infection. There is also the need to implement screening and treatment of
      hepatitis among pregnant women. A call was made for concerted efforts to be put
      together by all stakeholders towards addressing some of the structural barriers,
      including criminalization of drug use, discrimination and stigma that people
      living with viral hepatitis face. Finally, the need for greater advocacy was
      highlighted to enable access to therapy of viral hepatitis at lower cost than
      currently prevails. Implementation of these resolutions will help in achieving
      the target of eliminating viral hepatitis as a public health threat.

PMID- 30288322
TI  - Hepatitis C in Eastern Europe and Central Asia: a survey of epidemiology,
      treatment access and civil society activity in eleven countries.
AB  - Introduction: The 16 countries of the Eastern Europe and Central Asia (EECA)
      region are home to 6.6 million people in need of treatment for chronic hepatitis
      C virus (HCV) infection. Because of transformational change in HCV treatment,
      global efforts to address HCV are accelerating. Given its large regional burden,
      the EECA needs to ensure its inclusion in and benefit from any new developments.
      Methods: Our 2015-16 survey aimed to collect and report on epidemiology,
      treatment access (including drug registration and prices, national HCV guidelines
      and treatment program coverage) and pertinent civil society organization (CSO)
      activities in 11 countries in the EECA. Results: Major gaps in epidemiological
      data exist; reported anti-HCV prevalence ranged from 1.5 to 7.5% for the general
      population, 22.7 to 70-95% for people who inject drugs (PWID) and 18 to 80% for
      people living with HIV (PLHIV). Ten countries (91% of the sample) have registered
      one or more of the second-generation, direct-acting antiviral medications (DAA)
      for potential interferon-free treatment. However, intellectual property issues
      and prices limit access to these drugs. In 2014, HCV programs in the surveyed
      countries covered only 0.15% of the total number of people in need of treatment.
      CSO-driven, international donor-funded programs are starting to fulfill needs of
      PWID and PLHIV. Conclusions: As feasible curative HCV treatment is now available,
      and given the significant regional disease burden, EECA countries need to ensure
      HCV surveillance and DAA availability at affordable prices in order to expand
      treatment and prevent the onward transmission of the infection. EECA CSOs have
      demonstrated their capacity to play a crucial role in advancing HCV issues, and
      they should continue leveraging these issues for the benefit of individual
      patients and public health in general.

PMID- 30288324
TI  - "B in IT" - a community-based model for the management of hepatitis B patients in
      primary care clinics using a novel web-based clinical tool.
AB  - Background: The current model of care for the treatment of chronic hepatitis B
      (CHB) in Australia is through specialist Hepatology or Infectious Diseases
      clinics, and limited accredited primary care practices. Capacity is limited, and
      less than 5% of Australians living with CHB currently access therapy. Increasing
      treatment uptake is an urgent area of clinical need. Nucleos(t)ide analogue
      therapy is safe and effective treatment for CHB that is suitable for community
      prescribing. We have evaluated the success of a community-based model for the
      management of CHB in primary care clinics using a novel web-based clinical tool.
      Methods: Using guidelines set out by the Gastroenterological Society of
      Australia, we developed an interactive online clinical management tool for the
      shared care of patients with CHB in primary care clinics, with remote oversight
      from tertiary hospital-based hepatologists and a project officer. We call this
      model of care the "B in IT" program. Suitable patients were referred from the
      specialist liver clinic back to primary care for ongoing management. Compliance
      with recommended appointments, pathology tests and ultrasounds of patients
      enrolled in "B in IT" was assessed and compared to that of the same patients
      prior to community discharge, as well as a matched control group of CHB
      outpatients continuing to attend a specialist clinic. Results: Thirty patients
      with CHB were enrolled in the "B in IT" program. Compliance with attending
      scheduled appointments within 1 month of the suggested date was 87% across all
      115 visits scheduled. Compliance with completing recommended pathology within 1
      month of the suggested date was 94% and compliance with completing recommended
      liver ultrasounds for cancer screening within 1 month of the suggested date was
      89%. The compliance rates for visit attendance and ultrasound completion were
      significantly higher than the control patient group (p < 0.0001) and the "B in
      IT" patients prior to community discharge (p = 0.002 and p = 0.039,
      respectively). Conclusions: The "B in IT" program's novel web-based clinical tool
      supports primary care physicians to treat and monitor patients with CHB. This
      program promotes community-based care and increases system capacity for the
      clinical care of people living with CHB.

PMID- 30288323
TI  - A school-based intervention of screening a movie to increase hepatitis B
      vaccination levels among students in Uttar Pradesh, India: impact on knowledge,
      awareness, attitudes and vaccination levels.
AB  - Background: India is home to one in 14 of all chronic hepatitis B virus (HBV)
      cases, meaning that it is important to develop HBV interventions that are
      applicable in the Indian context. Vaccination is the foremost tool for
      interrupting the HBV infection cycle. HBV vaccination was not included in India's
      government-sponsored expanded immunisation program until 2011, and many children
      born earlier remain unvaccinated. This study sought to observe the impact of the
      HOPE Initiative's school-based intervention to increase vaccination coverage by
      increasing HBV awareness among students in Lucknow, Uttar Pradesh. Methods: At
      430 schools in the administrative areas within and surrounding Lucknow, students
      viewed an educational documentary film on HBV and completed two questionnaires,
      one immediately before the screening and the other six weeks later. Both
      questionnaires asked the same 14 questions, which were organized into five
      domains: knowledge of the magnitude of the problem of HBV; knowledge of modes of
      HBV transmission; knowledge of consequences of HBV infection; awareness of HBV;
      and attitudes regarding HBV. The baseline questionnaire also asked students
      whether they had been vaccinated against HBV. At two-year follow-up, researchers
      measured vaccination levels at a subset of 30 intervention schools and six non
      intervention schools to further assess the impact of the intervention. Results:
      Baseline questionnaires were completed by 11,250 students, and post-intervention
      questionnaires, by 9698 students. Scores for knowledge about the magnitude of the
      HBV problem improved from 41% at baseline to 74% at follow-up, and scores for
      knowledge about modes of transmission, from 38% to 75% (p < 0.05 for both). The
      baseline HBV vaccination level among students receiving the intervention was 21%.
      Two years after the intervention, 45% of students (N = 4284) reported being
      vaccinated at intervention schools compared to 22% (N = 1264) at non-intervention
      schools. Conclusions: The observed increases in HBV awareness, knowledge and
      vaccination levels in this study indicate that school-based interventions can be
      used to achieve higher vaccination coverage among Indian children. The
      documentary film was found to be an affordable tool for reaching large audiences.
      More studies are needed to validate the impact of this intervention and to
      explore its applicability to other social causes.

PMID- 30288325
TI  - Post-infection viral superinfection technology could treat HBV and HCV patients
      with unmet needs.
AB  - Background: Viral hepatitis deaths from acute infection, cirrhosis, and liver
      cancer have risen from the tenth to the seventh leading cause of death worldwide
      between 1990 and 2013. Even in the oral direct acting antiviral (DAA) agent era
      there are still large numbers of patients with unmet needs. Medications approved
      for treatment of chronic hepatitis B virus (HBV) infection do not eradicate HBV
      often requiring treatment for life associated with risks of adverse reactions,
      drug resistance, nonadherence, and increased cost. Although DAAs increased
      virologic cure rates well over 90% in all hepatitis C virus (HCV) genotypes, HCV
      infection still cannot be cured in a small but significant minority of patients.
      While most of the medical issues of HCV treatment have been solved, the current
      costs of DAAs are prohibitive. Results: The post-infection viral superinfection
      treatment (SIT) platform technology has been clinically proven to be safe and
      effective to resolve acute and persistent viral infections in 42 HBV and HCV
      patients (20 HBV, 22 HCV), and in 4 decompensated patients (2 HBV, 2 HCV). SIT
      employs a non-pathogenic avian double stranded RNA (dsRNA) virus, a potent
      activator of antiviral gene responses. Unexpectedly, SIT is active against
      unrelated DNA (HBV) and RNA (HCV) viruses. SIT does not require lifelong therapy,
      which is a major advantage considering present HBV treatments. The new viral drug
      candidate (R903/78) is homogeneously produced by reverse genetics in Vero cells.
      R903/78 has exceptional pH and temperature stability and also excellent long-term
      stability; therefore, it can be orally administered, stored and shipped without
      freezing. Since R903/78 is easy to stockpile, the post-infection SIT could also
      alleviate the logistic hurdles of surge capacity in vaccine production during
      viral pandemics. Conclusion: To help large number of HBV and HCV patients with
      unmet needs, broad-spectrum antiviral drugs effective against whole classes of
      viruses are urgently needed. The innovative SIT technological platform will be a
      great additional armament to conquer viral hepatitis, which is still a major
      cause of death and disability worldwide.

PMID- 30288326
TI  - Uptake of hepatitis B-HIV co-infection screening and management in a resource
      limited setting.
AB  - Background: WHO hepatitis B guidelines recommend testing all new HIV patients,
      treating them accordingly or providing immunization. At the Infectious Diseases
      Institute (IDI) following an audit done in 2012, only 46% patients had been
      screened for hepatitis B with variable management plans therefore new internal
      guidelines were implemented. This study describes the uptake of hepatitis B
      screening and management of patients with hepatitis B and HIV con-infection after
      the implementation. Methods: Data included for all HIV positive patients in care
      at IDI by October 2015. Data are expressed as median with interquartile range
      (IQR) and percentages were compared using the chi square test. Statistical
      analysis was performed using STATA version 13. The IDI laboratory upper limit of
      normal for alanine aminotransferase (ALT) and aspartate aminotransferase (ASTs)
      was 40 IU/ml. Results: Number of hepatitis B screening tests increased from 800
      by 2012 to 1400 in 2015. By 2015 8042/8604(93.5%) patients had been screened for
      hepatitis B. Overall hepatitis B positive were 359 (4.6%). 166 (81.4%) hepatitis
      B positives were switched to a tenofovir (TDF) containing regimen. Conclusion:
      Our study confirms the importance of screening for hepatitis B and of using ART
      regimens containing tenofovir in hepatitis B co-infected patients. Whilst our
      program has made improvements in care still 18.6% of patients with hepatitis B
      were not on tenofovir regimens, 98.1% had no hepatitis B viral loads done.
      Clinicians should recognize the potential for hepatitis B in HIV positive
      patients and the importance of early diagnosis and treatment to ensure optimal
      management of cases and follow up.

PMID- 30288328
TI  - Re-evaluation of chronic hepatitis B and hepatitis C patients lost to follow-up:
      results of the Northern Holland hepatitis retrieval project.
AB  - Background: Many persons infected with Hepatitis B virus (HBV) and Hepatitis C
      virus (HCV) in the past are now lost to follow-up. The aim of the Northern
      Holland Hepatitis Retrieval Project (NHHRP) is to retrieve and re-evaluate
      persons previously diagnosed with HBV or HCV and bring them back into care.
      Chronic HBV infection was defined as two positive Hepatitis B surface antigen
      (HBsAg) tests within 6 months and chronic HCV infection with 2 positive HCV RNA
      tests by polymerase chain reaction (PCR). Methods: Data files of the local public
      health services and microbiology laboratory were explored to identify all
      registered HBV and HCV cases in the Alkmaar region, the Netherlands, for the past
      15 years. Identified cases were compared with patients currently known in our
      hospital. Patients without follow-up in primary or hospital care were approached
      via their primary health care physician and invited for evaluation at our
      hospital. Results: In total, 552 cases of HBV were identified. 356 (64.5%) had no
      follow-up. Only 113/356 (31.7%) were eligible for retrieval and 44.2% were
      evaluated in our hospital resulting in a change of management in 22/50 (44%) of
      patients. Four hundred ninety nine cases of HCV were identified, 150/499 (30.1%)
      were lost to follow-up. Only 20/150 (13.3%) were eligible for retrieval and 4/20
      (20%) were evaluated at our clinic. Resulting in a change of management in 3/4
      (75%). Conclusion: Only a limited part of HBV and HCV persons lost to follow-up
      is eligible for retrieval, nonetheless re-evaluation of these persons will lead
      to a change of management in the majority of persons.

PMID- 30288327
TI  - Design of the Prospective Real-world Outcomes Study of hepatic encephalopathy
      Patients' Experience on Rifaximin-alpha (PROSPER): an observational study among
      550 patients.
AB  - Background: Hepatic encephalopathy (HE) is one of the most important severe
      complications of liver cirrhosis. Thought to be caused by elevated blood levels
      of gut-derived neurotoxins (particularly ammonia) entering the brain, HE
      manifests as a wide range of neurological or psychiatric abnormalities, which
      increase the risk of mortality, result in substantial morbidity and negatively
      affect the quality of life (QoL) of both patients and their caregivers. HE is
      also associated with a substantial economic burden. Rifaximin-alpha 550 mg is a
      locally acting oral antibiotic that reduces the effects of ammonia-producing
      intestinal flora, and which is used to help reduce the recurrence of overt HE.
      The efficacy of rifaximin-alpha 550 mg was established in a randomised controlled
      trial and long-term extension study. However, 'real-world' evidence is also
      required to assess how this efficacy may translate into effectiveness in clinical
      practice, including the potential impact of treatment on healthcare resource
      utilisation. Methods: The Prospective Real-world Outcomes Study of HE Patients'
      Experience on Rifaximin-alpha 550 mg (PROSPER) is a multinational, multicentre,
      observational study that will be conducted under real-world clinical practice
      conditions. Comprising a retrospective phase (up to 12 months) and a prospective
      phase (up to 24 months), and employing a robust statistical methodology, PROSPER
      has been specifically designed to minimise the bias associated with observational
      studies. The primary endpoint will be the effect of rifaximin-alpha 550 mg
      treatment on HE- and liver-related hospitalisation rate and duration of
      hospitalisation. Secondary endpoints will include comprehensive assessments of
      the impact of treatment on the QoL and workplace productivity of patients and
      caregivers, a global assessment of treatment effectiveness and
      safety/tolerability. Approximately 550 patients will be enrolled. Conclusions:
      PROSPER will provide valuable real-world information on the effectiveness of
      rifaximin-alpha 550 mg in reducing the recurrence of HE, and its impact on the
      QoL and work productivity of patients and their caregivers. By providing data on
      both the direct costs (e.g., hospitalisation rate, duration of hospitalisation)
      and indirect costs (such as work productivity) of HE, PROSPER should help confirm
      whether rifaximin-alpha 550 mg treatment represents a good use of economic
      resources. Trial registration: ClinicalTrials.gov identifier NCT02488993.

PMID- 30288329
TI  - Racial/ethnic- and county-specific prevalence of chronic hepatitis B and its
      burden in California.
AB  - Background: In the United States, the highest burden of chronic hepatitis B (CHB)
      and CHB-related liver cancer is in the state of California, primarily in the San
      Francisco (SF) Bay and Los Angeles (LA) areas. The aim of this study was to
      estimate county-specific hepatitis B surface antigen (HBsAg) prevalence and
      quantify CHB cases by age, race/ethnicity, nativity, and disease activity status.
      Methods: Twelve counties in SF Bay Area and three large counties in LA area were
      included for this analysis. Race/ethnicity-specific prevalence of HBsAg for each
      county and the state of California as a whole, was estimated by including
      prevalence data from the National Health and Nutrition Examination Survey and
      various studies that estimated HBsAg prevalence in US and foreign-born Asian
      Pacific Islanders, Hispanic, and Black populations. In addition, clinical data of
      2000 consecutive CHB patients (collected between 2009 and 2014) from a large
      clinical consortium in the SF Bay area were used to calculate the age-specific
      disease burden. Results: Of the 15 counties analyzed, SF had the highest HBsAg
      prevalence (1.78%), followed by Santa Clara (1.63%) and Alameda (1.45%). The
      majority of CHB cases were estimated to be in LA County (83,770), followed by
      Santa Clara (31,273), and Alameda (23,764). Among the CHB cases, 12.7% is active
      HBeAg positive, 24.2% is active HBeAg negative, and 10.6% has cirrhosis.
      Conclusion: This study confirms and quantifies the current burden of CHB in high
      endemic counties in the state of California using population-level estimates
      combined with clinical data including those from the community.

PMID- 30288330
TI  - Hepatitis C virus prevention and care for drug injectors: the French approach.
AB  - After France removed hepatitis C treatment reimbursement restrictions on 25 May
      2016, an expert report presented recommendations, which focused on vulnerable
      groups including people who inject drugs (PWID). This commentary presents the key
      points of the chapter with a particular focus on policy. Thanks to the official
      lifting of restrictions based on disease stage and to the excellent efficacy and
      tolerance of the new DAA (Direct-Acting Antivirals) among PWID, the main issue is
      to improve the HCV care cascade. In France, many HCV-infected PWID, especially
      active/current PWID, remain undiagnosed and unlinked to care. Our challenge is to
      improve HCV screening by point of care testing (POCT), outreach methods with
      mobile teams, rapid tests, FibroScan, etc. and to provide PWID with appropriate
      services in all the settings they attend, such as drug treatment or harm
      reduction services, social services, prisons, etc. Another important issue is the
      prevention of reinfection through comprehensive and long-term follow-up. The
      report recommends a new national policy: testing and treating PWID as a priority,
      since this is the best way to eliminate HCV infection. It requires a global
      strategy consisting of combined and long-term interventions: prevention,
      outreach, screening, DAA, drug treatment programs including opiate substitution
      treatment (OST) and various harm reduction programs, including needle exchange
      programs (NEP). Ideally, these services should be delivered in the same place
      with an integrated approach. This should lead to meeting the national objective
      set by the government of eliminating hepatitis C by 2025.

PMID- 30288331
TI  - Achieving a hepatitis C cure: a qualitative exploration of the experiences and
      meanings of achieving a hepatitis C cure using the direct acting antivirals in
      Australia.
AB  - Background: Universal access to the hepatitis C direct acting antiviral (DAAs)
      regimens presents a unique opportunity to eliminate hepatitis C in Australia.
      Large numbers of Australians have already been cured using these treatments,
      however, the numbers presenting for treatment have begun to plateau. This study
      explored how people experienced and understood being cured of hepatitis C, with
      the aim of informing interventions to increase uptake of DAA treatment among
      people with hepatitis C. Methods: This qualitative study used semi-structured
      interviews to explore the experiences of people with hepatitis C taking DAAs
      accessing both hospital and community clinics. Interviews were conducted 12 weeks
      after treatment completion. Participants were asked to reflect on their
      experience of living with hepatitis C, their reasons for seeking treatment, and
      their experience of, DAA treatments. Participants were also asked to reflect on
      the meaning of being cured, and how they shared this experience with their peers.
      Interviews were transcribed verbatim and key themes were identified using
      inductive thematic analysis. Results: Twenty participants were interviewed. While
      participants described a range of physical health benefits of achieving a
      hepatitis C cure it was an improved sense of psychological wellbeing that had the
      most significant impact on participants' lives. The majority described their
      relief about no longer living with the burden of an uncertain future due to
      anxiety about developing liver disease or cancer, as well as fear of infecting
      others. Participants who had a past history of injecting drug use, described
      being cured as a way to break the connection with their past. Participants who
      were current injectors raised concerns about re-infection. Conclusion: Feeling
      "normal" and not infectious allows people to live with reduced psychological
      distress, in addition to the physical benefits of no longer being at risk of
      developing serious liver disease. Future engagement strategies targeting people
      who are not accessing hepatitis health care need to promote the lived experience
      of being cured and the substantial psychological, and physical health benefits,
      offered by achieving a cure. Interventions aimed at people who are currently
      injecting also need to highlight the availability of re-treatment in conjunction
      with primary prevention strategies.

PMID- 30288332
TI  - Drug consumption rooms (DCRs) as a setting to address hepatitis C - findings from
      an international online survey.
AB  - Background: Prevalence of Hepatitis C Virus (HCV) among people who inject drugs
      (PWID) is high. Risky injecting behaviours have been found to decrease in drug
      consumption rooms (DCRs) and supervised injecting facilities (SIFs), yet HCV
      prevention and treatment in these settings have not been extensively explored.
      Methods: To determine the range and scope of HCV prevention and treatment options
      in these services, we assessed DCR/SIF operational features, their clients'
      characteristics and the HCV-related services they provide. A comprehensive online
      survey was sent to the managers of the 91 DCRs/SIFs that were operating globally
      as of September 2016. A descriptive cross-country analysis of the main DCR/SIF
      characteristics was conducted and bivariate logistic models were used to assess
      factors associated with enhanced HCV service provision. Results: Forty-nine valid
      responses were retrieved from DCRs/SIFs in all countries where they were
      established at the time of the survey (Australia, Canada, Denmark, France,
      Germany, Luxembourg, Netherlands, Norway, Spain and Switzerland).
      Internationally, the operational capacities of DCRs/SIFs varied in terms of
      funding, location, size and staffing, but their clients all shared common
      features of vulnerability and marginalisation. Estimated HCV prevalence rates
      were around 60%. Among a range of health and social services and referrals to
      other programs, most DCRs/SIFs provided HCV testing onsite (65%) and/or offered
      liver monitoring or disease management (54%). HCV treatment onsite was offered or
      was planned to be offered by 21% of DCRs/SIFs. HCV testing onsite was associated
      with provision of other services addressing blood-borne diseases and HCV
      treatment was linked to the provision of OST. HCV disease management was
      associated with employing a nurse at a DCR/SIF and HCV treatment was associated
      with employing a medical doctor. Conclusions: DCRs/SIFs offer easy-to-access HCV
      related services for PWID. The availability of onsite medical professionals and
      provision of support and education to non-medical staff are key to enhanced
      provision of HCV-related services in DCRs/SIFs. Funding and support for HCV
      treatment at the community level, via low-threshold services such as DCRs/SIFs,
      are worthy of action.

PMID- 30288333
TI  - Seroprevalence of hepatitis B and C in Nepal: a systematic review (1973-2017).
AB  - Introduction: Hepatitis B and C represent an important co-infection for people
      living with HIV worldwide. Nepal wants to be part of the international
      mobilization for viral hepatitis elimination, and has pursued better
      understanding of the epidemic in its territory through scientific research.
      Methods: We performed a systematic review of seroprevalence studies hepatitis B
      and C in Nepal following the PRISMA 2009 Flow Diagram. Results: Fifty-four
      scientific publications and reports were selected for this review. Nearly a
      quarter of these documents have been issued in recent years and many are authored
      by non-governmental organizations in Nepal. The collective of information
      displays a wide range of alarming prevalence rates, particularly for girls and
      women survivors of human trafficking and a progressive participation of civil
      society in viral hepatitis epidemiology research in the country. Conclusion: This
      paper presents a most complete review of hepatitis B and C and HIV co-infection
      prevalence studies in different population groups from 1973 to 2016. A
      comprehensive analysis of the epidemiology and apparent trends in public health
      research and policy making in Nepal are also addressed in this document. We
      expect this to be a most important tool for improvements in future interventions
      for both epidemics in the country.

PMID- 30288334
TI  - Strategies for achieving viral hepatitis C micro-elimination in the Netherlands.
AB  - The Netherlands is striving to achieve national elimination of the hepatitis C
      virus (HCV) as one of the first countries worldwide. The favorable HCV
      epidemiology with both low prevalence and incidence, together with access to care
      and treatment, present excellent conditions to further build on towards this
      objective. The Dutch national plan on viral hepatitis, introduced in 2016,
      defines targets in the HCV healthcare cascade and provides a structural framework
      for the development of elimination activities. Since many different stakeholders
      are involved in HCV care in the Netherlands, focus has been placed on micro
      elimination initiatives as a pragmatic and efficient approach. These numerous
      micro-eliminations projects have brought the Netherlands closer to HCV
      elimination. In the near future, efforts specifically have to be made in order to
      optimize case-finding strategies and to successfully accomplish the nationwide
      implementation of the registration and monitoring system of viral hepatitis mono
      infections, before this final goal can be reached. The upcoming years will then
      elucidate if the Dutch' hands on approach has resulted in sufficient progress
      against HCV and if the Netherlands will lead the way towards nationwide HCV
      elimination.

PMID- 30288335
TI  - The Community Health Experience Model-value generation from person-centered
      health transaction network.
AB  - Background: Network society is creating new opportunities for value generation in
      all areas of our lives: new collaborative methods and tools are increasingly
      available for use by closely connected individuals and organizations. The
      stakeholders of the health ecosystem are potential winners of this networking
      process as a consequence of the increase in knowledge about health value
      generation supported by teamwork and collaborative approaches in this field. Case
      Presentation: In this paper, we focus on the transactional nature of health value
      generation networks. First, we analyze the transactions in the networks. We then
      propose a design structure-the Community Health Experience Model-for effective
      person-centered health value generation networks. In the second phase of the
      work, we describe how the system design of the complete transaction network was
      tested in a real-life pilot environment focusing on fall prevention in
      individuals with osteoporosis.As a result of the network-based collaborative
      service approach, fall risk decreased by 11.8% and the number of falls decreased
      by 4.5% within 3 months. Regarding the major health experience outcomes, self
      evaluated condition-specific health literacy improved from 7.85 to 8.26 (an
      improvement of 0.41), while self-evaluated condition-specific self-management
      capability changed from 7.25 to 8.06 (0.81 improvement). Conclusions: In
      conclusion, the proposed Community Health Experience Model is a novel and
      promising approach to designing the structure of more effective and efficient
      health services and collaborative networks.

PMID- 30288336
TI  - Pediatric Meningoencephaloceles Endoscopic Endonasal Repair: Our Experience.
AB  - Background: Pediatric patients presenting with a nasal mass is uncommon and a
      high index of suspicion for it to be a meningoencephalocele is essential.
      Majority of these are congenital and require early intervention owing to the risk
      of meningitis. Surgery in these cases is very challenging because of the risk of
      anesthesia and limited space. Objective: This study aimed to describe our
      technique and experience in managing pediatric meningoencephaloceles. Methods: A
      retrospective study of 19 pediatric patients (age ranging from 40-day-old infants
      to 11.5-year-old children) was conducted at our tertiary care center from January
      2012 to February 2017. Patients presenting with an intranasal
      meningoencephalocele were treated by endoscopic approach, using otological
      microinstruments. After detailed imaging and clinical evaluation, a tailored
      repair, using fat/fascia/cartilage, a multilayer closure, was carried out in all
      cases. Results: All patients had a successful repair and recovery, except for one
      death following an episode of convulsion. There was a minor circumferential
      narrowing of the nasal vestibule and synechia formation in 2 of our cases.
      Conclusion: Transnasal endoscopic repair of meningoencephalocele is minimally
      invasive. It avoids permanent anosmia and is cosmetic. A combination of
      miniaturized instruments and a 4-mm 0 degrees  nasal endoscope gives excellent
      visual field and an adequate working space. Owing to the larger defects in
      congenital meningoencephaloceles, a multilayer repair provides excellent
      outcomes.

PMID- 30288337
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1177/2152656718783630.].

PMID- 30288338
TI  - Iridium Catalysts for Acceptorless Dehydrogenation of Alcohols to Carboxylic
      Acids: Scope and Mechanism.
AB  - We introduce iridium-based conditions for the conversion of primary alcohols to
      potassium carboxylates (or carboxylic acids) in the presence of potassium
      hydroxide and either [Ir(2-PyCH2(C4H5N2))(COD)]OTf (1) or [Ir(2-PyCH2PBu2
      t)(COD)]OTf (2). The method provides both aliphatic and benzylic carboxylates in
      high yield and with outstanding functional group tolerance. We illustrate the
      application of this method to a diverse variety of primary alcohols, including
      those involving heterocycles and even free amines. Complex 2 reacts with alcohols
      to form crystallographically-characterized catalytic intermediates [IrH(eta 1,eta
      3-C8H12)(2-PyCH2PtBu2)] (2a) and [Ir2H3(CO)(2-PyCH2PtBu2){MU-(C5H3N)CH2PtBu2}]
      (2c). The unexpected similarities in reactivities of 1 and 2 in this reaction,
      along with synthetic studies on several of our iridium intermediates, enable us
      to form a general proposal of the mechanisms of catalyst activation that govern
      the disparate reactivities of 1 and 2, respectively in glycerol and formic acid
      dehydrogenation. Moreover, careful analysis of the organic intermediates in the
      oxidation sequence enable new insights into the role of Tishchenko and Cannizzaro
      reactions in the overall oxidation.

PMID- 30288339
TI  - Organ-specific metastases obtained by culturing colorectal cancer cells on tissue
      specific decellularized scaffolds.
AB  - Metastatic disease remains the primary cause of mortality in cancer patients. Yet
      the number of available in vitro models to study metastasis is limited by
      challenges in the recapitulation of the metastatic microenvironment in vitro, and
      by difficulties in maintaining colonized-tissue specificity in the expansion and
      maintenance of metastatic cells. Here, we show that decellularized scaffolds that
      retain tissue-specific extracellular-matrix (ECM) components and bound signaling
      molecules enable, when seeded with colorectal cancer (CRC) cells, the spontaneous
      formation of three-dimensional cell colonies that histologically, molecularly and
      phenotypically resemble in vivo metastases. Lung and liver metastases obtained by
      culturing CRC cells on, respectively, liver and lung decellularized scaffolds
      retained their tissue-specific tropism when injected in mice. We also found that
      the engineered metastases contained signet ring cells, which has not previously
      been observed ex vivo. A culture system with tissue-specific decellularized
      scaffolds represents a simple and powerful approach for the study of organ
      specific cancer metastases.

PMID- 30288340
TI  - Long-term outcomes of a phase I study of agonist CD40 antibody and CTLA-4
      blockade in patients with metastatic melanoma.
AB  - We report long-term clinical outcomes and immune responses observed from a phase
      1 trial of agonist CD40 monoclonal antibody (mAb) and blocking CTLA-4 mAb in
      patients with metastatic melanoma. Twenty-four patients previously untreated with
      checkpoint blockade were enrolled. The agonistic CD40 mAb CP-870,893 and the CTLA
      4 blocking mAb tremelimumab were dosed concomitantly every 3 weeks and 12 weeks,
      respectively, across four dose combinations. Two patients developed dose-limiting
      grade 3 immune-mediated colitis that led to the definition of the maximum
      tolerated dose (MTD). Other immune-mediated toxicity included uveitis (n = 1),
      hypophysitis (n = 1), hypothyroidism (n = 2), and grade 3 cytokine release
      syndrome (CRS) (n = 1). The estimated MTD was 0.2 mg/kg of CP-870,893 and 10
      mg/kg of tremelimumab. In 22 evaluable patients, the objective response rate
      (ORR) was 27.3%: two patients (9.1%) had complete responses (CR) and four (18.2%)
      patients had partial responses (PR). With a median follow-up of 45 months, the
      median progression-free survival (PFS) was 3.2 months (95% CI, 1.3-5.1 months)
      and median overall survival (OS) was 23.6 months (95% CI, 11.7-35.5 months). Nine
      patients are long-term survivors (> 3 years), 8 of whom subsequently received
      other therapy including PD-1 mAb, surgery, or radiation therapy. Elevated
      baseline soluble CD25 was associated with shorter OS. Immunologically, treatment
      was associated with evidence of T cell activation and increased tumor T cell
      infiltration that was accomplished without therapeutic PD-1/PD-L1 blockade. These
      results suggest opportunities for immune activation and cancer immunotherapy
      beyond PD-1.

PMID- 30288341
TI  - A novel function of API5 (apoptosis inhibitor 5), TLR4-dependent activation of
      antigen presenting cells.
AB  - Dendritic cell (DC)-based vaccines are recognized as a promising
      immunotherapeutic strategy against cancer. Various adjuvants are often
      incorporated to enhance the modest immunogenicity of DC vaccines. More
      specifically, many of the commonly used adjuvants are derived from bacteria. In
      the current study, we evaluate the use of apoptosis inhibitor 5 (API5), a damage
      associated molecular pattern expressed by many human cancer cells, as a novel DC
      vaccine adjuvant. We showed that API5 can prompt activation and maturation of DCs
      and activate NFkB by stimulating the Toll-like receptor signaling pathway. We
      also demonstrated that vaccination with API5-treated DCs pulsed with OVA, E7, or
      AH1-A5 peptides led to the generation of OVA, E7, or AH1-A5-specific CD8 + T
      cells and memory T cells, which is associated with long term tumor protection and
      antitumor effects in mice, against EG.7, TC-1, and CT26 tumors. Additionally, we
      determined that API5-mediated DC activation and immune stimulation are dependent
      on TLR4. Lastly, we showed that the API5 protein sequence fragment that is
      proximal to its leucine zipper motif is responsible for the adjuvant effects
      exerted by API5. Our data provide evidence that support the use of API5 as a
      promising adjuvant for DC-based therapies, which can be applied in combination
      with other cancer therapies. Most notably, our results further support the
      continued investigation of human-based adjuvants.

PMID- 30288342
TI  - A point mutation in the Ncr1 signal peptide impairs the development of innate
      lymphoid cell subsets.
AB  - NKp46 (CD335) is a surface receptor shared by both human and mouse natural killer
      (NK) cells and innate lymphoid cells (ILCs) that transduces activating signals
      necessary to eliminate virus-infected cells and tumors. Here, we describe a
      spontaneous point mutation of cysteine to arginine (C14R) in the signal peptide
      of the NKp46 protein in congenic Ly5.1 mice and the newly generated NCRB6C14R
      strain. Ly5.1C14R NK cells expressed similar levels of Ncr1 mRNA as C57BL/6, but
      showed impaired surface NKp46 and reduced ability to control melanoma tumors in
      vivo. Expression of the mutant NKp46C14R in 293T cells showed that NKp46 protein
      trafficking to the cell surface was compromised. Although Ly5.1C14R mice had
      normal number of NK cells, they showed an increased number of early maturation
      stage NK cells. CD49a+ILC1s were also increased but these cells lacked the
      expression of TRAIL. ILC3s that expressed NKp46 were not detectable and were not
      apparent when examined by T-bet expression. Thus, the C14R mutation reveals that
      NKp46 is important for NK cell and ILC differentiation, maturation and function.
      Significance Innate lymphoid cells (ILCs) play important roles in immune
      protection. Various subsets of ILCs express the activating receptor NKp46 which
      is capable of recognizing pathogen derived and tumor ligands and is necessary for
      immune protection. Here, we describe a spontaneous point mutation in the signal
      peptide of the NKp46 protein in congenic Ly5.1 mice which are widely used for
      tracking cells in vivo. This Ncr1 C14R mutation impairs NKp46 surface expression
      resulting in destabilization of Ncr1 and accumulation of NKp46 in the endoplasmic
      reticulum. Loss of stable NKp46 expression impaired the maturation of NKp46+ ILCs
      and altered the expression of TRAIL and T-bet in ILC1 and ILC3, respectively.

PMID- 30288343
TI  - Tumor infiltrating CD19+ B lymphocytes predict prognostic and therapeutic
      benefits in metastatic renal cell carcinoma patients treated with tyrosine kinase
      inhibitors.
AB  - The objective response rate (ORR) of tyrosine kinase inhibitors (TKIs) therapy in
      metastatic renal cell cancer (mRCC) patients was not satisfactory. Effective
      indicator of mRCC patient selection for TKI therapy is urgently needed. The
      function of tumor infiltrating B lymphocytes (TIBs) in tumor immune elimination
      is still unclear. We aim to investigate the prognostic and predictive value of
      TIBs for TKI therapy in mRCC patients in this study. 108 eligible patients
      treated with TKI were enrolled in this study. TIBs was estimated by
      immunohistochemical staining of CD19 in the resected tumor, and its relationship
      with clinicopathological features, clinical outcomes and CD8+ tumor infiltrating
      T lymphocytes (CD8+ TILs) were evaluated. Associations between the expression
      level of CD19 and CD8+ TILs associated cytotoxic effectors were also assessed in
      public databases. Results showed TIBs positive infiltration predicted better
      therapeutic response to sunitinib (p = 0.006), longer overall survival (OS) (p <
      0.001) and progression-free survival (PFS) (p = 0.028) in mRCC patients.
      Combining TIBs and International Metastatic Renal-Cell Carcinoma Database
      Consortium (IMDC) model showed a better predict value of OS in TKI-treated mRCC
      patients than IMDC model alone. We also found a positive correlation between TIBs
      and CD8+ TILs (p < 0.001). Patients with both cells high infiltration showed
      markedly better OS compared with those infiltrated by CD8+ T cells alone (p =
      0.015). To conclude, TIBs density was not only an independent prognostic factor
      for mRCC patients, but also a predictive marker for TKI therapy response. It may
      potently enhance the antitumor effect by recruiting and activating CD8+ TILs in
      mRCC.

PMID- 30288344
TI  - Brain tumor-initiating cells export tenascin-C associated with exosomes to
      suppress T cell activity.
AB  - The dismal prognosis of glioblastoma is attributed in part to the existence of
      stem-like brain tumor-initiating cells (BTICs) that are highly radio- and chemo
      resistant. New approaches such as therapies that reprogram compromised immune
      cells against BTICs are needed. Effective immunotherapies in glioblastoma,
      however, remain elusive unless the mechanisms of immunosuppression by the tumor
      are better understood. Here, we describe that while the conditioned media of
      activated T lymphocytes reduce the growth capacity of BTICs, this growth
      suppression was abrogated in live co-culture of BTICs with T cells. We present
      evidence that BTICs produce the extracellular matrix protein tenascin-C (TNC) to
      inhibit T cell activity in live co-culture. In human glioblastoma brain
      specimens, TNC was widely deposited in the vicinity of T cells. Mechanistically,
      TNC inhibited T cell proliferation through interaction with alpha5beta1 and
      alphavbeta6 integrins on T lymphocytes associated with reduced mTOR signaling.
      Strikingly, TNC was exported out of BTICs associated with exosomes, and TNC
      depleted exosomes suppressed T cell responses to a significantly lesser extent
      than control. Finally, we found that circulating exosomes from glioblastoma
      patients contained more TNC and T cell-suppressive activity than those from
      control individuals. Taken together, our study establishes a novel
      immunosuppressive role for TNC associated with BTIC-secreted exosomes to affect
      local and distal T lymphocyte immunity.

PMID- 30288345
TI  - Impact of chemotactic factors and receptors on the cancer immune infiltrate: a
      bioinformatics study revealing homogeneity and heterogeneity among patient
      cohorts.
AB  - Multiple soluble factors including proteins (in particular chemokines), non
      proteinaceous factors released by dead cells, as well as receptors for such
      factors (in particular chemokine receptors, formyl peptide receptors and
      purinergic receptors), influence the recruitment of distinct cell subsets into
      the tumor microenvironment. We performed an extensive bioinformatic analysis on
      tumor specimens from 5953 cancer patients to correlate the mRNA expression levels
      of chemotactic factors/receptors with the density of immune cell types
      infiltrating the malignant lesions. This meta-analysis, which included specimens
      from breast, colorectal, lung, ovary and head and neck carcinomas as well as
      melanomas, revealed that a subset of chemotactic factors/receptors exhibited a
      positive and reproducible correlation with several infiltrating cell types across
      various solid cancers, revealing a universal pattern of association. Hence, this
      meta-analysis distinguishes between homogeneous associations that occur across
      different cancer types and heterogeneous correlations, that are specific of one
      organ. Importantly, in four out of five breast cancer cohorts for which clinical
      data were available, the levels of expression of chemotactic factors/receptors
      that exhibited universal (rather than organ-specific) positive correlations with
      the immune infiltrate had a positive impact on the response to neoadjuvant
      chemotherapy. These results support the notion that general (rather than organ
      specific) rules governing the recruitment of immune cells into the tumor bed are
      particularly important in determining local immunosurveillance and response to
      therapy.

PMID- 30288346
TI  - Epigenetic treatment of multiple myeloma mediates tumor intrinsic and extrinsic
      immunomodulatory effects.
AB  - Immune evasion is an important driver of disease progression in the plasma cell
      malignancy multiple myeloma. Recent work highlights the potential of epigenetic
      modulating agents as tool to enhance anti-tumor immunity. The immune modulating
      effects of the combination of a DNA methyltransferase inhibitor and a histone
      deacetylase inhibitor in multiple myeloma is insufficiently characterized.
      Therefore, we used the murine immunocompetent 5T33MM model to investigate
      hallmarks of immunogenic cell death as well as alterations in the immune cell
      constitution in the bone marrow of diseased mice in response to the DNA
      methyltransferase inhibitor decitabine and the histone deacetylase inhibitor
      quisinostat. Vaccination of mice with 5T33 cells treated with epigenetic
      compounds delayed tumor development upon a subsequent tumor challenge. In vitro,
      epigenetic treatment induced ecto-calreticulin and CD47, as well as a type I
      interferon response. Moreover, treated 5T33vt cells triggered dendritic cell
      maturation. The combination of decitabine and quisinostat in vivo resulted in
      combinatory anti-myeloma effects. In vivo, epigenetic treatment increased tumoral
      ecto-calreticulin and decreased CD47 and PD-L1 expression, increased dendritic
      cell maturation and reduced CD11b positive cells. Moreover, epigenetic treatment
      induced a temporal increase in presence of CD8-positive and CD4-positive T cells
      with naive and memory-like phenotypes based on CD62L and CD44 expression levels,
      and reduced expression of exhaustion markers PD-1 and TIM3. In conclusion, a
      combination of a DNA methyltransferase inhibitor and a histone deacetylase
      inhibitor increased the immunogenicity of myeloma cells and altered the immune
      cell constitution in the bone marrow of myeloma-bearing mice.

PMID- 30288348
TI  - The prognostic and predictive value of IKZF1 and IKZF3 expression in T-cells in
      patients with multiple myeloma.
AB  - Purpose: While recent studies described the role of IKZF1/3 proteins in multiple
      myeloma (MM) cells, few have highlighted the significance of IKZF1/3 expression
      in T-cells. In this study we examine the prognostic and predictive value of
      IKZF1/3 expression in T-cells in patients with MM stage III. Experimental design:
      We analysed the IKZF1/3 expression levels in T-cells from 45 MM stage I (MMI) and
      50 newly diagnosed MM stage III (MMIII) patients, according to Durie-Salmon
      staging system, by flow cytometry to examine their prognostic and predictive
      value. We also combined in vivo observations with in vitro assays to determine
      the effect of IKZF1/3 expression on the T-cell immunophenotype and anti-tumour T
      cell response in 162 MMIII patients. Results: We found that high IKZF3, but not
      IKZF1, expression in T-cells correlates with superior overall survival in MMIII
      patients treated with immunomodulatory drugs (thalidomide, lenalidomide and
      pomalidomide). Moreover, we show that higher IKZF3 expression in T-cells inhibits
      myeloma-specific T-cell response in vitro and that the immunophenotype of
      patients with high IKZF3 expression shows features that are contrary to the
      changes induced by immunomodulatory drugs. Although we observed higher IKZF3
      expression levels in T-cells from patients with MMIII compared to MMI, IKZF3
      expression was unaffected by the tumour microenvironment. Conclusion: In
      conclusion, IKZF3 expression in T-cells is a predictive value for clinical
      outcome in MMIII patients treated with immunomodulatory drugs due to its profound
      modulation of T-cell functionality.

PMID- 30288347
TI  - Combination with SGT-53 overcomes tumor resistance to a checkpoint inhibitor.
AB  - The tumor suppressor p53 responds to genotoxic and oncogenic stresses by inducing
      cell cycle arrest and apoptosis. Recent studies suggest that p53 also
      participates in the regulation of cellular immune responses. Here, we have
      investigated the potential of p53 gene therapy to augment immune checkpoint
      inhibition by combining an anti-programmed cell death protein 1 (PD1) antibody
      with SGT-53, our investigational nanomedicine carrying a plasmid encoding human
      wild-type p53. In three syngeneic mouse tumor models examined including a breast
      cancer, a non-small cell lung carcinoma, and a glioblastoma, SGT-53 sensitized
      otherwise refractory tumors to anti-PD1 antibody. The involvement of p53 in
      enhancing anti-PD1 immunotherapy appears to be multifaceted, since SGT-53
      treatment increased tumor immunogenicity, enhanced both innate and adaptive
      immune responses, and reduced tumor-induced immunosuppression in a 4T1 breast
      tumor model. In addition, SGT-53 alleviates a fatal xenogeneic hypersensitivity
      associated with the anti-PD1 antibody in this model. Our data suggest that
      restoring p53 function by SGT-53 is able to boost anti-tumor immunity to augment
      anti-PD1 therapy by sensitizing tumors otherwise insensitive to anti-PD1
      immunotherapy while reducing immune-related adverse events.

PMID- 30288349
TI  - Daratumumab induces CD38 internalization and impairs myeloma cell adhesion.
AB  - Daratumumab (Dara), a human immunoglobulin G1 kappa (IgG1kappa) monoclonal anti
      CD38 antibody, has been approved by the U.S. Food and Drug Administration for the
      treatment of relapsed multiple myeloma (MM) as a single agent as well as in
      combination with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PI).
      Although the scientific rationale behind the use of Dara in combination with
      IMiDs has been extensively explored, the molecular mechanisms underlying Dara-PI
      regimens have not yet been investigated. Here, we demonstrate that CD38 on the
      surface of MM cells is rapidly internalized after Dara treatment; we also show
      that Dara treatment impairs MM cell adhesion, an effect that can be rescued by
      using the endocytosis inhibitor Dynasore. Finally, we show that Dara potentiates
      bortezomib (BTZ) killing of MM cells in vitro and in vivo, independent of its
      function as an immune activator. In conclusion, our data show that Dara impairs
      MM cell adhesion, which results in an increased sensitivity of MM to proteasome
      inhibition.

PMID- 30288351
TI  - Therapeutic vaccination with 4-1BB co-stimulation eradicates mouse acute myeloid
      leukemia.
AB  - Immunomodulatory therapies can effectively control haematological malignancies.
      Previously we reported the effectiveness of combination immunotherapies that
      centre on 4-1BB-targeted co-stimulation of CD8 + T cells, particularly when
      simultaneously harnessing the immune adjuvant properties of Natural Killer T
      (NKT) cells. The objective of this study was to assess the effectiveness of
      agonistic anti-4-1BB antibody-based combination therapy against two aggressive
      forms of acute myeloid leukemia (AML). Anti-4-1BB treatment alone resulted in
      transient suppression of established AML-ETO9a tumor growth in 50% of mice,
      however the majority of these mice subsequently succumbed to disease. Combining
      alpha-galactosylceramide (alpha-GalCer)-loaded tumor cell vaccination with anti-4
      1BB antibody treatment increased the proportion of responding mice to 100%, and
      protection led to long-term, tumor-free survival, demonstrating complete
      eradication of AML. This finding was extended to established mixed lymphocytic
      leukemia (MLL)-AF9 tumors, whereby vaccine plus anti-4-1BB combination similarly
      resulted in 100% protection. The addition of anti-PD-1 to anti-4-1BB treatment,
      although improving survival outcomes compared to anti-4-1BB alone, was not as
      effective as NKT cell vaccination. The effectiveness of 4-1BB combination
      therapies was dependent on IFN-gamma signaling within host cells, but not tumors.
      Vaccine plus anti-4-1BB therapy elicited potent generation of functional effector
      and memory CD8 + T cells in all tumor-associated organs. Therapy induced KLRG1+
      effector CD8 T cells were the most effective at controlling disease. We show that
      combining NKT cell-targeting vaccination with anti-4-1BB provides excellent
      therapeutic responses against AML and MLL in mice, and these results will guide
      ongoing efforts in finding immunotherapeutic solutions against acute myeloid
      leukemias.

PMID- 30288350
TI  - EBV infection determines the immune hallmarks of plasmablastic lymphoma.
AB  - Despite recent therapeutic progress, plasmablastic lymphoma (PBL), a distinct
      entity of high grade B cell lymphoma, is still an aggressive lymphoma with
      adverse prognosis. PBL commonly occurs in patients with HIV infection and PBL
      cells frequently express Epstein Barr virus (EBV) genome with type I latency.
      Occasionally however, PBL may develop in patients with an immunodepressed status
      without EBV and HIV infection. The aim of this study was to determine which PBL
      patients may benefit from the emerging strategies of immune checkpoint blockade.
      Here, we produced and analyzed the transcriptomic profiles of such tumors to
      address this question. Unsupervised hierarchical clustering analysis of PBL
      samples revealed they segregate according to their tumor EBV-status. Moreover,
      EBV+ PBL displays abundant leucocyte infiltrates and T-cell activation
      signatures, together with high expression levels of mRNA and protein markers of
      immune escape. This suggests that EBV infection induce an anti-viral cytotoxic
      immunity which progressively exhausts T lymphocytes and promotes the tolerogenic
      microenvironment of PBL. Hence, most EBV+ PBL patients presenting an early stage
      of cancer immune-editing process appear as the most eligible patients for immune
      checkpoint blockade therapies.

PMID- 30288352
TI  - Potent therapeutic efficacy of an alphavirus replicon DNA vaccine expressing
      human papilloma virus E6 and E7 antigens.
AB  - Cervical cancer develops as a result of infection with high-risk human
      papillomavirus (HPV) through persistent expression of early proteins E6 and E7.
      Our group pioneered a recombinant viral vector system based on Semliki Forest
      virus (SFV) for vaccination against cervical cancer. The most striking benefit of
      this alphavirus vector-based vaccine platform is its high potency. DNA vaccines
      on the other hand, have a major advantage with respect to ease of production. In
      this study, the benefits associated with both SFV-based vaccines and DNA vaccines
      were combined with the development of a DNA-launched RNA replicon (DREP) vaccine
      targeting cervical cancer. Using intradermal delivery followed by
      electroporation, we demonstrated that DREP encoding for E6,7 (DREP-E6,7) induced
      effective, therapeutic antitumor immunity. While immunizations with a
      conventional DNA vaccine did not prevent tumor outgrowth, immunization with a 200
      fold lower equimolar dose of DREP (0.05 ug of DREP) resulted in approximately 85%
      of tumor-free mice. To overcome the safety concern of potential malignant
      transformation at the vaccination site, we evaluated the anti-tumor effect of a
      DREP vaccine encoding a shuffled version of E7 (DREP-E7sh). DREP-E7sh delayed
      tumor growth yet not to the same extent as DREP-E6,7. In addition, inclusion of a
      helper cassette and an ER targeting signal (sigHelp) did not significantly
      further enhance the suppression of tumor outgrowth in the long term, albeit
      exhibiting better tumor control early after immunization. Collectively, this
      study points towards the clinical evaluation of DREP encoding HPV antigens as a
      potent immunotherapy for patients with HPV16 (pre)-malignancies.

PMID- 30288353
TI  - MUC16 mutations improve patients' prognosis by enhancing the infiltration and
      antitumor immunity of cytotoxic T lymphocytes in the endometrial cancer
      microenvironment.
AB  - The incidence and mortality rates of endometrial cancer are increasing during
      recent years. CA125 (gene symbol MUC16) is a well-known diagnostic and prognostic
      serum marker of endometrial cancer. High serum CA125 level is associated with
      poor prognosis. MUC16 is one of the most frequently mutated genes in endometrial
      cancer. However, the potential relationship and underlying mechanism between
      MUC16 mutations and endometrial cancer patients' prognosis and disease
      progression remain unclear. In present study, we analyzed the whole exome
      sequencing data, RNA sequencing data and patients' clinical information in TCGA
      database and demonstrated that MUC16 mutational status was an independent
      prognostic factor for endometrial cancer patients. Patients with somatic MUC16
      mutations had a prolonged overall survival time. MUC16 mutations promoted
      patients' antitumor immune responses. Cytotoxic immune cells mediated pathways
      were enriched in endometrial cancer samples with MUC16 mutations. Elevation of
      two pathways, NO2-dependent IL 12 pathway in NK cells and T cytotoxic cell
      surface molecules, significantly correlated with a higher rate of MUC16 mutations
      and a significantly favorable patients' prognosis. An increased level of
      cytotoxic T lymphocytes, not NK cells, infiltration was observed in the tumor
      microenvironment of patients with MUC16 mutations. High expression of molecular
      markers of T cells and CD8+ T cells associated with a higher rate of MUC16
      mutations and a better patients' prognosis. These findings may provide deeper
      insight into potential endometrial cancer immunotherapy approaches.

PMID- 30288354
TI  - WEE1 kinase inhibition reverses G2/M cell cycle checkpoint activation to
      sensitize cancer cells to immunotherapy.
AB  - Intrinsic resistance to cytotoxic T-lymphocyte (CTL) killing limits responses to
      immune activating anti-cancer therapies. Here, we established that activation of
      the G2/M cell cycle checkpoint results in tumor cell cycle pause and protection
      from granzyme B-induced cell death. This was reversed with WEE1 kinase
      inhibition, leading to enhanced CTL killing of antigen-positive tumor cells.
      Similarly, but at a later time point, cell cycle pause following TNFalpha
      exposure was reversed with WEE1 kinase inhibition, leading to CTL transmembrane
      TNFalpha-dependent induction of apoptosis and necroptosis in bystander antigen
      negative tumor cells. Results were reproducible in models of oral cavity
      carcinoma, melanoma and colon adenocarcinoma harboring variable Tp53 genomic
      alterations. WEE1 kinase inhibition sensitized tumors to PD-1 mAb immune
      checkpoint blockade in vivo, resulting in CD8+-dependent rejection of established
      tumors harboring antigen-positive or mixed antigen-positive and negative tumor
      cells. Together, these data describe activation of the G2/M cell cycle checkpoint
      in response to early and late CTL products as a mechanism of resistance to CTL
      killing, and provide pre-clinical rationale for the clinical combination of
      agents that inhibit cell cycle checkpoints and activate anti-tumor immunity.

PMID- 30288355
TI  - Potentiating cancer vaccine efficacy in liver cancer.
AB  - Hepatocellular carcinoma (HCC) is the most common liver malignancy with a poor
      prognosis and an overall 5-year survival rate of approximately 5-6%. This is due
      because standard of care treatment options are limited and none of them shows a
      sufficient efficacy. HCC is an "inflammation-induced cancer" and preliminary
      preclinical and clinical data suggest that immunotherapeutic approaches may be a
      good alternative candidate for the treatment of HCC patients improving the dismal
      prognosis associated with this cancer. However, recent findings strongly suggest
      that an optimal immunotherapy in HCC requires the combination of an immune
      activator with immune modulators, aiming at compensating the strong liver immune
      suppressive microenvironment. One of the most promising strategy could be
      represented by the combination of a cancer vaccine with immunomodulatory drugs,
      such as chemotherapy and checkpoint inhibitors. Very limited examples of such
      combinatorial strategies have been evaluated in HCC to date, because HCC easily
      develops resistance to standard chemotherapy, which is also poorly tolerated by
      patients with liver cirrhosis. The present review describes the most update
      knowledge in this field.

PMID- 30288357
TI  - The comprehensive molecular landscape of the immunologic co-stimulator B7 and
      TNFR ligand receptor families in colorectal cancer: immunotherapeutic
      implications with microsatellite instability.
AB  - Immunotherapy is reportedly effective in a subset of colorectal cancers (CRCs)
      with high microsatellite instability (MSI-H). Exploring the expression patterns
      and clinical values of immunologic molecules is critical in defining the specific
      responsive candidates. Here, we performed comprehensive molecular profiling of
      the B7 and TNFR family genes across 6 CRC datasets with over 1,000 patients'
      details using cBioPortal TCGA data. About 20% of patients had B7 and TNFR family
      gene alterations. The frequency of B7 gene mutations (2.2%-5%) were similar to
      copy number alterations (0.53%-5.46%). TNFR amplifications were relatively more
      common (5.45-11.32%) than that of B7 (0.09-2.73%). B7 and TNFR gene mRNAs were
      upregulated in 26% of cases (102/379) and 16% of cases (61/379), respectively.
      The mRNA levels of B7 and TNFR genes were inversely correlated with promoter
      methylation status. Clinically, both B7-H3 and TNFSF7 mRNA overexpression were
      associated with unfavorable clinical outcomes, and the B7-H3 expression was
      increased gradually in cases with gene amplifications. Moreover, patients with
      MSI-H had significantly higher PD-L1 or PD-1 expression. Most importantly, in MSI
      H group, patients with PD-L1 or PD-1 upregulation had poorer survivals than those
      with PD-L1/PD-1 downregulation. This is the first study drawing the immune
      landscapes of the co-stimulator B7 and TNFR families in CRC and showing that MSI
      H patients with PD-1/PD-L1 upregulation are associated with poor clinical
      outcomes, providing potential markers to stratify patients responsive to immune
      checkpoint therapy.

PMID- 30288356
TI  - Ex vivo AKT-inhibition facilitates generation of polyfunctional stem cell memory
      like CD8+ T cells for adoptive immunotherapy.
AB  - Adoptive T cell therapy has shown clinical potential for patients with cancer,
      though effective treatment is dependent on longevity and potency of the exploited
      tumor-reactive T cells. Previously, we showed that ex vivo inhibition of AKT
      using the research compound Akt-inhibitor VIII retained differentiation and
      improved functionality of minor histocompatibility antigen (MiHA)-specific CD8+ T
      cells. Here, we compared a panel of clinically applicable AKT-inhibitors with an
      allosteric or adenosine triphosphate-competitive mode of action. We analyzed
      phenotype, functionality, metabolism and transcriptome of AKT-inhibited CD8+ T
      cells using different T cell activation models. Most inhibitors facilitated T
      cell expansion while preserving an early memory phenotype, reflected by
      maintenance of CD62L, CCR7 and CXCR4 expression. Moreover, transcriptome
      profiling revealed that AKT-inhibited CD8+ T cells clustered closely to naturally
      occurring stem cell-memory CD8+ T cells, while control T cells resembled effector
      memory T cells. Interestingly, AKT-inhibited CD8+ T cells showed enrichment of
      hypoxia-associated genes, which was consistent with enhanced glycolytic function.
      Notably, AKT-inhibition during MiHA-specific CD8+ T cell priming uncoupled
      preservation of early memory differentiation from ex vivo expansion. Furthermore,
      AKT-inhibited MiHA-specific CD8+ T cells showed increased polyfunctionality with
      co-secretion of IFN-gamma and IL-2 upon antigen recall. Together, these data
      demonstrate that AKT-inhibitors with different modality of action promote the ex
      vivo generation of stem cell memory-like CD8+ T cells with a unique metabolic
      profile and retained polyfunctionality. Akt-inhibitor VIII and GDC-0068
      outperformed other inhibitors, and are therefore promising candidates for ex vivo
      generation of superior tumor-reactive T cells for adoptive immunotherapy in
      cancer patients.

PMID- 30288358
TI  - TGF-beta1 programmed myeloid-derived suppressor cells (MDSC) acquire immune
      stimulating and tumor killing activity capable of rejecting established tumors in
      combination with radiotherapy.
AB  - Cancer-induced myeloid-derived suppressor cells (MDSC) play an important role in
      tumor immune evasion. MDSC programming or polarization has been proposed as a
      strategy for leveraging the developmental plasticity of myeloid cells to reverse
      MDSC immune suppressive functions, or cause them to acquire anti-tumor activity.
      While MDSC derived ex vivo from murine bone marrow precursor cells with tumor
      conditioned medium efficiently suppressed T cell proliferation, MDSC derived from
      conditioned medium in presence of TGF-beta1 (TGFbeta-MDSC) acquired a novel
      immune-stimulatory phenotype, losing the ability to inhibit T cell proliferation
      and acquiring enhanced antigen-presenting capability. Altered immune function was
      associated with SMAD-2 dependent upregulation of maturation and costimulatory
      molecules, and downregulation of inducible nitric oxide synthase (iNOS), an
      effector mechanism of immunosuppression. TGFbeta-MDSC also upregulated FAS-ligand
      expression, leading to FAS-dependent killing of murine human papillomavirus (HPV)
      associated head and neck cancer cells and tumor spheroids in vitro and anti-tumor
      activity in vivo. Radiation upregulated FAS expression on tumor cells, and the
      combination of radiotherapy and intratumoral injection of TGFbeta-MDSC strongly
      enhanced class I expression on tumor cells and induction of HPV E7 tetramer
      positive CD8 + T cells, leading to clearance of established tumors and long-term
      survival. TGFbeta-MDSC derived from human PBMC with tumor conditioned medium also
      lost immunosuppressive function and acquired tumor-killing activity. Thus,
      TGFbeta1 mediated programming of nascent MDSC leads to a potent anti-tumor
      phenotype potentially suitable for adoptive immunotherapy.

PMID- 30288359
TI  - Formation and phenotypic characterization of CD49a, CD49b and CD103 expressing
      CD8 T cell populations in human metastatic melanoma.
AB  - Integrins alpha1beta1 (CD49a), alpha2beta1 (CD49b) and alphaEbeta7 (CD103)
      mediate retention of lymphocytes in peripheral tissues, and their expression is
      upregulated on tumor infiltrating lymphocytes (TIL) compared to circulating
      lymphocytes. Little is known about what induces expression of these retention
      integrins (RI) nor whether RI define subsets in the tumor microenvironment (TME)
      with a specific phenotype. Human metastatic melanoma-derived CD8 TIL could be
      grouped into five subpopulations based on RI expression patterns: RIneg, CD49a+
      only, CD49a+CD49b+, CD49a+CD103+, or positive for all three RI. A significantly
      larger fraction of the CD49a+ only subpopulation expressed multiple effector
      cytokines, whereas CD49a+CD103+ and CD49a+CD49b+ cells expressed IFNgamma only.
      RIneg and CD49a+CD49b+CD103+ CD8 TIL subsets expressed significantly less
      effector cytokines overall. Interestingly, however, CD49a+CD49b+CD103+ CD8
      expressed lowest CD127, and highest levels of perforin and exhaustion markers PD
      1 and Tim3, suggesting selective exhaustion rather than conversion to memory. To
      gain insight into RI expression induction, normal donor PBMC were cultured with T
      cell receptor (TCR) stimulation and/or cytokines. TCR stimulation alone induced
      two RI+ cell populations: CD49a single positive and CD49a+CD49b+ cells. TNFalpha
      and IL-2 each were capable of inducing these populations. Addition of TGFbeta to
      TCR stimulation generated two additional populations; CD49a+CD49bnegCD103+ and
      CD49a+CD49b+CD103+. Taken together, our findings identify opportunities to
      modulate RI expression in the TME by cytokine therapies and to generate subsets
      with a specific RI repertoire in the interest of augmenting immune therapies for
      cancer or for modulating other immune-related diseases such as autoimmune
      diseases.

PMID- 30288361
TI  - Combination immune checkpoint blockade as an effective therapy for mesothelioma.
AB  - Mesothelioma is an aggressive asbestos induced cancer with extremely poor
      prognosis and limited treatment options. Immune checkpoint blockade (ICPB) has
      demonstrated effective therapy in melanoma and is now being applied to other
      cancers, including mesothelioma. However, the efficacy of ICPB and which immune
      checkpoint combinations constitute the best therapeutic option for mesothelioma
      have yet to be fully elucidated. Here, we used our well characterised
      mesothelioma tumour model to investigate the efficacy of different ICBP
      treatments to generate effective therapy for mesothelioma. We show that tumour
      resident regulatory T cell co-express high levels of CTLA-4, OX40 and GITR
      relative to T effector subsets and that these receptors are co-expressed on a
      large proportion of cells. Targeting any of CTLA-4, OX40 or GITR individually
      generated effective responses against mesothelioma. Furthermore, the combination
      of alphaCTLA-4 and alphaOX40 was synergistic, with an increase in complete tumour
      regressions from 20% to 80%. Other combinations did not synergise to enhance
      treatment outcomes. Finally, an early pattern in T cell response was predictive
      of response, with activation status and ICP receptor expression profile of T
      effector cells harvested from tumour and dLN correlating with response to
      immunotherapy. Taken together, these data demonstrate that combination ICPB can
      work synergistically to induce strong, durable immunity against mesothelioma in
      an animal model.

PMID- 30288360
TI  - IL-6 augments IL-4-induced polarization of primary human macrophages through
      synergy of STAT3, STAT6 and BATF transcription factors.
AB  - Macrophages in the tumor microenvironment respond to complex cytokine signals.
      How these responses shape the phenotype of tumor-associated macrophages (TAMs) is
      incompletely understood. Here we explored how cytokines of the tumor milieu,
      interleukin (IL)-6 and IL-4, interact to influence target gene expression in
      primary human monocyte-derived macrophages (hMDMs). We show that dual stimulation
      with IL-4 and IL-6 synergistically modified gene expression. Among the
      synergistically induced genes are several targets with known pro-tumorigenic
      properties, such as CC-chemokine ligand 18 (CCL18), transforming growth factor
      alpha (TGFA) or CD274 (programmed cell death 1 ligand 1 (PD-L1)). We found that
      transcription factors of the signal transducer and activator of transcription
      (STAT) family, STAT3 and STAT6 bind regulatory regions of synergistically induced
      genes in close vicinity. STAT3 and STAT6 co-binding further induces the basic
      leucine zipper ATF-like transcription factor (BATF), which participates in
      synergistic induction of target gene expression. Functional analyses revealed
      increased MCF-7 and MDA-MB 231 tumor cell motility in response to conditioned
      media from co-treated hMDMs compared to cells incubated with media from single
      cytokine-treated hMDMs. Flow cytometric analysis of T cell populations upon co
      culture with hMDMs polarized by different cytokines indicated that dual
      stimulation promoted immunosuppressive properties of hMDMs in a PD-L1-dependent
      manner. Analysis of clinical data revealed increased expression of BATF together
      with TAM markers in tumor stroma of breast cancer patients as compared to normal
      breast tissue stroma. Collectively, our findings suggest that IL-4 and IL-6
      cooperate to alter the human macrophage transcriptome, endowing hMDMs with pro
      tumorigenic properties.

PMID- 30288363
TI  - Macrophages in radiation injury: a new therapeutic target.
AB  - Radiotherapy can induce toxicity in healthy tissues such as radiation-induced
      fibrosis (RIF), and macrophages are proposed as new profibrogenic cells. In this
      Point-of-View, we summarize the role of the immune response in ionizing radiation
      injury, and we focus on macrophages as a new therapeutic target in RIF.

PMID- 30288362
TI  - Prognostic role of pretreatment circulating MDSCs in patients with solid
      malignancies: A meta-analysis of 40 studies.
AB  - Myeloid-derived suppressor cells (MDSCs) have been shown to contribute to tumor
      progression, mainly through immune suppression. Inverse correlations have been
      observed between MDSC levels and patient survival for various malignancies. The
      purpose of this meta-analysis was to evaluate the prognostic value of
      pretreatment circulating MDSCs. We searched MEDLINE and EMBASE from their
      inceptions to September 2017 to identify relevant articles. Using a fixed or
      random effects model, pooled hazard ratios (HRs) were estimated for overall
      survival (OS) and combined disease-free survival, progression-free survival, and
      recurrence-free survival (DFS/PFS/RFS). A total of 40 studies comprising 2721
      were included. For solid tumors, high levels of pretreatment circulating MDSCs
      were significantly associated with worse OS (HR = 1.796, 95% CI = 1.587-2.032)
      and DFS/PFS/RFS (HR = 2.459, 95% CI = 2.018-2.997). Breast cancer showed the
      largest association between high MDSC levels and worse OS (pooled HR = 3.053).
      Elevated MDSCs were also associated with worse OS for mixed-stage tumors (pooled
      HR = 1.659) and advanced-stage tumors (pooled HR = 2.337). Furthermore, both
      monocytic-MDSCs (M-MDSCs) and granulocytic or polymorphonuclear (PMN-MDSCs)
      showed negative associations with survival outcomes. Overall, high levels of
      pretreatment circulating MDSCs negatively influenced survival in most cancers.
      Pretreatment circulating MDSCs should be taken into account to further improve
      prognostic evaluation and develop novel therapeutic strategies.

PMID- 30288364
TI  - Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor
      immune microenvironments.
AB  - Tobacco smoking causes DNA damages in epithelial cells and immune dysfunction in
      the lung, which collectively contribute to lung carcinogenesis and progression.
      However, potential mechanisms by which tumor-infiltrating immune cells contribute
      to lung cancer survival and their differential contributions in ever-smokers and
      never-smokers are not well studied. Here, we performed integrative analysis of 11
      lung cancer gene-expression datasets, including 1,111 lung adenocarcinomas and
      200 adjacent normal lung samples. Distinct pathways were altered in lung
      carcinogenesis in ever-smokers and never-smokers. Never-smoker patients had a
      better outcome than ever-smoker patients. We characterized compositional patterns
      of 21 types of immune cells in lung adenocarcinomas and revealed the complex
      association between immune cell composition and clinical outcomes. Interestingly,
      we found two subsets of immune cells, mast cells and CD4+ memory T cells, which
      had completely opposite associations with outcomes in resting and activated
      status. We further discovered that several chemokines and their associated
      receptors (e.g., CXCL11-CX3CR1 axis) were selectively altered in lung tumors in
      response to cigarette smoking and their abundances showed stronger correlation
      with fractions of these immune subsets in ever-smokers than never-smokers. The
      status switched from the resting to activated forms in mast cells and CD4+ memory
      T cells might manifest some important processes induced by cigarette smoking
      during tumor development and progression. Our findings suggested that aberrant
      activation of mast cells and CD4+ memory T cells plays crucial roles in cigarette
      smoking-induced immune dysfunction in the lung, which contributes to tumor
      development and progression.

PMID- 30288365
TI  - Treatment-naive HPV+ head and neck cancers display a T-cell-inflamed phenotype
      distinct from their HPV- counterparts that has implications for immunotherapy.
AB  - Cancers progress when the immune system fails to identify and eliminate malignant
      cells. Recognition of this, combined with advances in tumor immunology, has
      allowed development of therapies that induce effective anti-tumor immune
      responses. For incompletely-understood reasons, effective responses to
      immunotherapy occur in some patients and not others. Head and neck squamous cell
      carcinomas (HNSCC) are a common cancer type that can be divided into two subsets
      based on human papillomavirus (HPV) status. HPV status is a strong predictor of
      positive clinical outcome. Expression of exogenous viral antigens by HPV+, but
      not HPV-, HNSCC allows direct comparison of the immune status (immune cell
      presence and characteristics) between these two otherwise anatomically-similar
      tumors. Using TCGA data, we compared the immune landscape between HPV+ and HPV-
      treatment-naive HNSCC. As compared to HPV- samples, HPV+ HNSCC exhibited a strong
      Th1 response characterized by increased infiltration with multiple types of
      immune cells and expression of their effector molecules. HPV+ HNSCC also
      expressed higher levels of CD39 and multiple T-cell exhaustion markers including
      LAG3, PD1, TIGIT, and TIM3 compared to HPV- HNSCC. Importantly, patients with
      higher expression of these exhaustion markers-indicative of a T-cell-inflamed
      tumor-correlated with markedly improved survival in HPV+, but not HPV-, HNSCC.
      Thus, profound differences exist between the immune landscape of HPV+ and HPV-
      HNSCC. These results suggest that immune checkpoint inhibitor therapy is a
      promising treatment strategy for HPV+ HNSCC, and that expression of immune
      checkpoint molecules could serve as a predictive biomarker of patient outcome in
      HPV+ HNSCC.

PMID- 30288367
TI  - Gender Differences and the Impact of Exposure to Violence on Depressive Symptoms
      and Sleep Habits among Young African American Adults.

PMID- 30288366
TI  - Black, White, and Gray: Macrophages in Skin Repair and Disease.
AB  - Purpose of Review: Macrophages alter their responses during the temporal stages
      of wound healing. During the inflammatory phase macrophages perform phagocytosis.
      During neovascularization macrophages activate angiogenesis. In the proliferation
      phase of wound healing, macrophages deposit extracellular matrix and during wound
      resolution macrophages phagocytize excessive cellular components. This review
      addresses how these changing phenotypes affect skin repair and disease. Recent
      Findings: Macrophages can determine the outcome of repair and can shift the
      normal wound healing response into fibrosis or chronic wounds. Emerging single
      cell technologies for the first time provide us with tools to uncover macrophage
      origin, heterogeneity and function. Summary: Macrophages may exist as one
      population where all cells alter their phenotype in response to signals from the
      microenvironment. Alternatively, macrophages may exist as distinct subsets that
      can control wound outcomes. A clarified understanding will strengthen our
      knowledge of skin biology and aid in the development of wound healing therapies.

PMID- 30288368
TI  - Melanoma Cell Death Mechanisms.
AB  - Over recent years, several new molecular and immunogenic therapeutic approaches
      to melanoma treatment have been approved and implemented in clinical practice.
      Mechanisms of resistance to these new therapies have become a major problem.
      Mutation-specific pharmacotherapy can result in simultaneous emergence of
      resistant clones at many separate body sites despite an initially positive
      therapeutic response. Additionally, treatments aimed at inducing apoptosis are
      subject to resistance due to escape through other known mechanisms of regulated
      cell death (RCD). In this review, we discuss the complexity in pharmacological
      manipulation of melanoma with c-Kit, BRAF, MEK, and/or mTOR mutant cell lines.
      This study also addresses melanoma evasion of cell death through modalities of
      RCD such as apoptosis, autophagy, and necroptosis. This study also examines new
      combination therapies which have been approved to target both cell cycle
      dysregulation and cell death pathways. Lastly, we recognize the importance of
      immunomodulation though manipulation of the body's natural killing mechanisms
      with CTLA4, PD1, and CSF1 inhibition. As we begin to recognize tumor cell
      activation of alternate pathways, evasion of programmed cell death, and
      manipulation of the tumor microenvironment, it is increasingly important to grasp
      the complexity of personalized therapy in melanoma treatment.

PMID- 30288369
TI  - Role of PET/CT in the Evaluation of Aortic Disease.
AB  - Positron emission tomography (PET) /computed tomography (CT) has been established
      as a standard imaging modality in the evaluation of malignancy. Although PET/CT
      has played a major role in the management of oncology patients, its clinical use
      has also increased for various disorders other than malignancy. Growing evidence
      shows that PET/CT images have many advantages in aortic disease as well. This
      review article addresses the potential role of PET/CT in diseases involving the
      aorta, emphasizing its usefulness with regard to acute thoracic aortic syndromes,
      aortic aneurysm, atherosclerotic lesions, aortitis and aortic tumors.

PMID- 30288370
TI  - Use of Combined Oral Contraceptives in Perimenopausal Women.
AB  - While perimenopausal women have low fecundity, they are still capable of becoming
      pregnant and the majority of pregnancies occurring during perimenopause are
      unintended pregnancies. Therefore, even during perimenopause, contraception must
      be used if unintended pregnancies are to be avoided. However, many perimenopausal
      women and healthcare providers believe that older people should not take combined
      oral contraceptives (COC) because doing so may be dangerous. However, to date,
      there is no evidence that taking COC presents an increased risk of cardiovascular
      events or breast cancer for middle-aged women as compared to other age groups,
      and in their recommendations, the Centers for Disease Control and Prevention
      (CDC) also do not list age itself as a contraindication for COC. Perimenopausal
      women often experience menstrual irregularity, heavy menstrual bleeding, and
      vasomotor symptoms. Taking COCs can help control these symptoms and significantly
      reduce the risk of ovarian cancer, endometrial cancer, and colorectal cancer. The
      objective of the present review is to examine the usage methods of COC among
      perimenopausal women and the health issues that may arise from taking COC in
      perimenopausal women.

PMID- 30288371
TI  - Effects of NADPH Oxidase Inhibitors and Mitochondria-Targeted Antioxidants on
      Amyloid beta1-42-Induced Neuronal Deaths in Mouse Mixed Cortical Cultures.
AB  - The Amyloid beta peptide (Abeta) is a main component of senile plaques in
      Alzheimer's disease. Currently, NADPH oxidase (NOX) and mitochondria are
      considered as primary sources of ROS induced by Abeta. However, the contribution
      of NOX and mitochondria to Abeta-induced ROS generation has not been well
      defined. To delineate the relative involvement of NOX and mitochondria in Abeta
      induced ROS generation and neuronal death in mouse cortical cultures, we examined
      the effect of NOX inhibitors, apocynin and AEBSF, and the mitochondria-targeted
      antioxidants (MTAs), mitotempol and mitoquinone, on Abeta-induced ROS generation
      and neuronal deaths. Cell death was assessed by measuring lactate dehydrogenase
      efflux in bathing media at 24 and 48 hrs after exposure to Abeta1-42. Abeta1-42
      induced dose- and time-dependent neuronal deaths in cortical cultures. Treatment
      with 20 uM Abeta1-42 markedly and continuously increased not only the DHE
      fluorescence (intracellular ROS signal), but also the DHR123 fluorescence
      (mitochondrial ROS signal) up to 8 hrs. Treatment with apocynin or AEBSF
      selectively suppressed the increase in DHE fluorescence, while treatment with
      mitotempol selectively suppressed the increase in DHR123 fluorescence. Each
      treatment with apocynin, AEBSF, mitotempol or mitoquinone significantly
      attenuated the Abeta1-42-induced neuronal deaths. However, any combined treatment
      with apocynin/AEBSF and mitotempol/mitoquinone failed to show additive effects.
      These findings indicate that 20 uM Abeta1-42 induces oxidative neuronal death via
      inducing mitochondrial ROS as well as NOX activation in mixed cortical cultures,
      but combined suppression of intracellular and mitochondrial ROS generation fail
      to show any additive neuroprotective effects against Abeta neurotoxicity.

PMID- 30288372
TI  - Effects of Ivabradine on Left Ventricular Systolic Function and Cardiac Fibrosis
      in Rat Myocardial Ischemia-Reperfusion Model.
AB  - We evaluated the effects of Ivabradine on left ventricle (LV) ejection fraction
      (EF) and LV infarcted tissue in the rat myocardial ischemia-reperfusion model.
      Twenty rats were randomly assigned to group 1 (ischemia-reperfusion, no
      treatment, n=10) and group 2 (ischemia-reperfusion + Ivabradine 10 mg/kg, n=10).
      Ivabradine was administered for 28 days. Echocardiography was performed at 7 days
      and at 28 days after the induction of ischemia-reperfusion injury. Cardiac
      fibrosis induced by ischemia-reperfusion injury was evaluated by Masson's
      trichrome staining. The infarct size was quantified using the Image J program. At
      the 28-day follow-up, LVEF was significantly higher (36.02+/-6.16% vs. 45.72+/
      2.62%, p<0.001) and fractional shortening was significantly higher (15.23+/-2.84%
      vs. 20.13+/-1.38%, p<0.001) in group 2 than group 1. Delta (28 day minus 7 day)
      EF was significantly higher in group 2 than group 1 (-4.36+/-3.49% vs. 4.31+/
      5.63%, p<0.001). Also, heart rate (beats/min) was significantly lower in group 2
      than group 1 (251.67+/-25.19 vs. 199.29+/-31.33, p=0.025). Group 2 had a smaller
      infarct size (40.70+/-8.94% vs. 30.19+/-5.89%, p<0.01) than group 1 at 28-day
      follow-up. Oral administration of Ivabradine could improve LV systolic function
      and reduce infarcted tissue area in rat myocardial ischemia-reperfusion model.

PMID- 30288373
TI  - The Predictive Value of Epstein-Barr Virus-Positivity in Patients Undergoing
      Gastrectomy Followed by Adjuvant Chemotherapy.
AB  - The present study evaluated the survival impact of standard adjuvant chemotherapy
      and prognostic differences between Epstein-Barr virus (EBV)-associated gastric
      cancer (EBVaGC) and EBV-negative gastric cancer (EBVnGC). A total of 276 patients
      were enrolled according to the following criteria: 1) pathologically diagnosed
      with primary gastric adenocarcinoma, 2) test results from EBV-encoded RNA in situ
      hybridization, 3) stage II/III according to the 7th edition of UICC/AJCC staging
      system for gastric cancer, and 4) postoperative adjuvant chemotherapy. Fifty-nine
      (21.4%) and 217 (78.6%) patients exhibited EBVaGC and EBVnGC, respectively, while
      129 (46.7%) patients were classified as stage II and 147 (53.3%) as stage III. As
      for adjuvant chemotherapy, 87 (31.5%) patients received capecitabine and
      oxaliplatin, while 189 (68.5%) received S-1 monotherapy. With a median follow-up
      duration of 21.3 (6.4-89.0) months, the estimated 3-year disease-free survival
      (DFS) and overall survival (OS) rates were 74.8% and 83.0%, respectively. In
      univariate analysis and multivariate analysis using a Cox proportional hazard
      model including age, gender, stage, Lauren classification, and the type of
      chemotherapy, EBV-positivity was not significantly associated with DFS (p-value=
      0.630) regardless of the type of chemotherapy. Therefore, no association was
      found between EBV positivity and the survival outcomes in patients with
      curatively resected gastric cancer who received standard adjuvant chemotherapy.

PMID- 30288374
TI  - Association of Coffee and Tea with Ferritin: Data from the Korean National Health
      and Nutrition Examination Survey (IV and V).
AB  - There have been few studies that have evaluated the association between coffee
      intake and iron in Korean population. Data from the Korean National Health and
      Nutrition Examination Survey (IV and V; 2007-2012) was used to investigate the
      association between coffee and green tea intake and serum ferritin levels in
      Korean adults. Beverage intake was assessed using a food frequency questionnaire.
      Multivariate linear regression was performed to evaluate the relationship between
      coffee and tea intake and serum ferritin levels, after adjusting for age, body
      mass index, education level, smoking status, alcohol consumption, physical
      activity, hypertension, diabetes mellitus, and daily iron intake. Coffee intake
      was negatively related to serum ferritin levels in both sexes. The multivariate
      adjusted geometric mean of serum ferritin level was 100.7 ng/mL (95% confidence
      interval [CI]: 98.2-103.4) in men drinking <1 coffee/day, and 92.2 ng/mL (95% CI:
      89.7-94.8) in those drinking >=3 coffees/day. In women, the equivalent serum
      ferritin levels were 35.6 ng/mL (95% CI: 34.8-36.4) and 28.9 ng/mL (95% CI: 27.8
      30.1). However, green tea intake was not related to serum ferritin levels. In
      conclusion, coffee consumption was associated with lower serum ferritin levels in
      Korean adults.

PMID- 30288377
TI  - An Unusual Adult Complex Congenital Heart Disease.

PMID- 30288375
TI  - Association between Smoking and Unintentional Injuries among Korean Adults.
AB  - Using a cross-sectional representative national survey, we evaluated the
      relationship between cigarette smoking and unintentional injuries among Korean
      adults. We used data from the 2009 Korean Community Health Survey. Smoking status
      was defined as never smokers, ex-smokers, and current smokers. Current smokers
      were categorized into light daily smokers (1-10 cigarettes/day), moderate daily
      smokers (11-20 cigarettes/day), or heavy daily smokers (>=21 cigarettes/day). We
      used the Poisson regression model with a robust variance estimation to estimate
      prevalence rate ratios (PRR) and corresponding 95% confidence interval (95% CI).
      After adjusting for demographic characteristics, socioeconomic variables,
      lifestyle variables, and health status variables, former smokers (PRR, 1.19, 95%
      CI 1.11-1.28), light daily smokers (PRR 1.22, 95% CI 1.13-1.32), moderate daily
      smokers (PRR 1.33, 95% CI 1.24-1.42), and heavy daily smokers (PRR 1.40, 95% CI
      1.25-1.57) had an increased risk for unintentional injuries compared with non
      smokers. In conclusion, cigarette smoking is associated with unintentional
      injuries in a dose-response manner in Korean adults. The findings suggest that
      community smoking cessation programs may reduce morbidity and mortality from
      unintentional injuries.

PMID- 30288378
TI  - Pneumomediastinum after Forceful Vomiting in a Patient with Diabetic
      Ketoacidosis.

PMID- 30288376
TI  - Predictors of Clinical Outcome in Patients with Angiographically Intermediate
      Lesions with Minimum Lumen Area Less than 4 mm2 Using Intravascular Ultrasound in
      Non-Proximal Epicardial Coronary Artery.
AB  - We investigated predictors of major adverse cardiac events (MACE) with two years
      after medical treatment for lesions with angiographically intermediate lesions
      with intravascular ultrasound (IVUS) minimum lumen area (MLA) <4 mm2 in non
      proximal epicardial coronary artery. We retrospectively enrolled 104 patients (57
      males, 62+/-10 years) with angiographically intermediate lesions (diameter
      stenosis 30-70%) with IVUS MLA <4 mm2 in the non-proximal epicardial coronary
      artery with a reference lumen diameter between 2.25 and 3.0 mm. We evaluated the
      incidences of major adverse cardiovascular events (MACE including death,
      myocardial infarction, target lesion and target vessel revascularizations, and
      cerebrovascular accident) two years after medical therapy. During the two-year
      follow-up, 15 MACEs (14.4%) (including 1 death, 2 myocardial infarctions, 10
      target vessel revascularizations, and 2 cerebrovascular accidents) occurred.
      Diabetes mellitus was more prevalent (46.7% vs. 18.0%, p=0.013) and statins were
      used less frequently in patients with MACE compared with those without MACE
      (40.0% vs. 71.9%, p=0.015). Independent predictors of MACEs with two years
      included diabetes mellitus (odds ratio [OR]=3.41; 95% CI=1.43-8.39, p=0.020) and
      non-statin therapy (OR=3.11; 95% CI=1.14-6.50, p=0.027). Long-term event rates
      are relatively low with only medical therapy without any intervention, so the cut
      off of IVUS MLA 4 mm2 might be too large to be applied for defining significant
      stenosis. The predictors of long-term MACE were diabetes mellitus and statin
      therapy in patients with angiographically intermediate lesions in non-proximal
      epicardial coronary artery.

PMID- 30288379
TI  - Minimal Change Disease Associated with Ingestion of Poison Sumac.

PMID- 30288381
TI  - The impact of diabetes mellitus on quality of life - differences between genders.
AB  - Objective: To determine whether there are gender differences in the impact of the
      disease in the quality of life of individuals with Diabetes Mellitus type 2.
      Methods: The sample consisted of 192 individuals distributed in equal numbers by
      gender. Data were collected between the months of August 2013 to May 2014, by
      sociodemographic and clinical questionnaires and instruments for assessing
      quality of life (PAID) and adherence to treatment. Results: The age of the
      patients ranged from 30 to 80 years old with a mean of 61 years of age (+/- 11).
      B-PAID scores were higher in men except in issues related to social support, but
      the differences were not statistically significant; 51.7% of the patients with
      good adherence to treatment were women and 48.3% were men. Conclusions: The
      perception of the impact of diabetes in the quality of life of individuals in the
      present study, measured by the B-PAID instrument, showed that the highest scores
      predominate in men, that is, they have a higher degree of emotional distress than
      women. In the group with good adherence to treatment, there is a greater number
      of individuals with higher PAID scores, especially in men. In the group with poor
      adherence to treatment, the number of individuals with a high degree of emotional
      distress was similar in both sexes. This research was approved by the Research
      Ethics Committee of UNIFESP, through Plataforma Brasil (Protocol number 103,384).

PMID- 30288380
TI  - Genotype and phenotype of salt-stimulated paraoxonase 1 (PON1) is associated with
      atherogenic indices in type 2 diabetes.
AB  - Background: Paraoxonase 1 (PON1) and lipid abnormalities contribute to the
      development of cardiovascular disease, which is the principal cause of mortality
      in patients with type 2 diabetes (T2D). Data are not available on the potential
      association between salt-stimulated activity of PON1 (PON1-salt) and the
      atherogenic indices in T2D, therefore, we focused on these associations and
      evaluated whether the functional variants PON1-Q192R and PON1-L55M influence the
      associations. Methods: Paraoxonase activity (PON1-para), arylesterase activity
      (PON1-aryl) and salt-stimulated activity (PON1-salt) were measured by
      spectrophotometric assays. The atherogenic index of plasma (AIP) was calculated
      from the log (TG/HDL-C). The genetic analyses were made by the restricted
      fragment length polymorphism after PCR amplification. Results: We observed that
      PON1-salt was negatively correlated with total cholesterol (TC)/HDL-C (r = 
      0.441,p = 0.006), LDL-C/HDL-C (r = -0.415, p = 0.011), and AIP (r = -0.422, p =
      0.009). Correlations between PON1-salt and all three atherogenic indices were
      significantly affected by PON1-L55M and PON1-Q192R. Linear regression showed that
      AIP (p = 0.002), LDL-C/HDL-C (p = 0.005), and TC/HDL-C (p = 0.002) were
      independently associated with PON1-salt. Based on Ridge regression, the
      standardized coefficients -0.358, -0.297, and - 0.044 were obtained for AIP, LDL
      C/HDL-C, and TC/HDL-C, respectively, and this shows that AIP could have more
      negative effect on PON1-salt than the others. Conclusions: The decreased PON1
      salt may be considered as a risk factor for atherosclerosis in T2D, therefore,
      understanding the associations between PON1-salt as an important although
      neglected property and atherogenic indices may be valuable in T2D. Accordingly,
      detection of PON1-salt status (phenotype and genotype) together with the
      atherogenic indices particularly AIP could be beneficial in identifying the
      increased atherogenicity in T2D.

PMID- 30288382
TI  - Circulating tumor DNA (ctDNA) in the era of personalized cancer therapy.
AB  - The heterogeneity of tumor is considered as a major difficulty to victorious
      personalized cancer medicine. There is an extremeneed of consistent response
      evaluation for in vivo tumor heterogeneity anditscoupledconflict mechanisms. In
      this occasion researchers will be able to keep pace withpredictive, preventive,
      personalized, and Participatory (P4) medicine for cancer managements. In fact
      tumor heterogeneity is a central part of cancer evolution,soin order to progress
      in understanding of the dynamics within a tumor some diagnostic apparatus should
      be improved. Latest molecular techniques like Next generation Sequencing (NGS)
      and ultra-deep sequencing could disclose some clones within a liquid tumor biopsy
      which mainly responsible of treatment resistance. Circulating tumor DNA (ctDNA)
      as a main component of liquid biopsy is agifted biomarker for cancer mutation
      tracking as well as profiling. Personalized medicine facilitate learning
      regarding to genetic pools of tumor and their possible respond to treatment which
      could be much easier by using of ctDNA.With this information,
      cliniciansarelooking forward to find the best strategies for prevention,
      screening, and treatment in the way of precision medicine. Currently, numerous
      clinical efficacy of such informative improved treatment are in hand. Here we
      represent the review of plasma-derived ctDNA studies use in personalized cancer
      managements.

PMID- 30288383
TI  - Development of a store-and-forward telescreening system of diabetic retinopathy:
      lessons learned from Iran.
AB  - Background: The present study describes the development and identity phases of a
      teleophthalmology system used for screening of diabetic retinopathy. Methods: A
      questionnaire was used to identify the main factors necessary for diagnosis of
      diabetic retinopathy and the features required for a teleophthalmology system. In
      the second phase, a web-based prototype of the system was designed using the data
      collected in the previous phase. In the final phase, the system was optimized
      based on the users' ideas and comments; then, it was evaluated through a standard
      usability testing questionnaire. Results: The results showed that the lowest
      average percentages were related to ethnicity (61%), optometrist's office address
      (61%), and consultant physician's office address (65%). A web-based prototype was
      designed using the Visual Studio and Dreamweaver programming tools. This system
      comprised patient identity data, medical history, clinical data, and retinal
      images of the patient. The mean score of usability testing and user satisfaction
      including specialists, residents, and optometrist was 7.3, 7.1 and 7.3 (out of a
      total 9), respectively. The evaluation results revealed that the system was
      classified as good. Conclusion: The telescreening system suggested in the current
      study could be helpful in timely diagnosis. Moreover, it would reduce the
      treatment costs and complexities. Regardless of the positive points of
      telemedicine systems, one of the most challenges in this study was the Internet
      infrastructure to design and apply the system. The future studies, therefore,
      could focus on the application of cell phone technology for rendering
      teleophthalmology.

PMID- 30288384
TI  - Acute phase ketosis-prone atypical diabetes is associated with a pro-inflammatory
      profile: a case-control study in a sub-Saharan African population.

PMID- 30288385
TI  - Obesity paradox on the survival of elderly patients with diabetes: an AHAP-based
      study.
AB  - Background and objectives: Overweight and obesity are among the important
      challenges in health issues and survival of elderly people. The current study
      aimed to evaluate the survival rate of elderly patients with diabetes, and its
      influencing factors, on the basis of body mass index (BMI). Methods and
      materials: The design of the current study was based on the Amirkola Health and
      Aging Project (AHAP) cohort. The 5-year survival rate of elderly people with
      diabetes and the factors that influence the mortality rate by Cox regression
      model were analyzed. Results: Out of 1616 elderly people who were evaluated in
      the current study, 501 (31%) had diabetes. The results showed that diabetes
      significantly increased the mortality rate (adjusted hazard ratio [HR] = 2.10;
      95% confidence interval [CI]: 1.57-2.81; P < 0.001). Furthermore, overweight (HR
      = 0.41; 95%CI: 0.24-0.75; P = 0.002), obesity (HR = 0.30; 95% CI: 0.41-0.63; P =
      0.002), history of diabetes (HR = 0.56; 95%CI: 0.34-0.93; P = 0.024), moderate
      and high physical activity level (HR = 0.36; 95%CI: 0.13-0.99; P = 0.049)
      decreased the risk of mortality and central obesity (HR = 1.76; 95% CI: 1.01
      3.11; P = 0.049), fasting blood sugar >=200 (HR = 2.46; 95% CI: 1.46-4.15; P <
      0.001), brain stroke, and neurological diseases (HR = 3.12; 95% CI: 1.78-5.49; P
      < 0.001) increased the risk of mortality. Conclusion: Although overweight and
      obesity significantly improved the risk of mortality in elderly patients with
      diabetes, central obesity is still considered as an important risk factor.

PMID- 30288386
TI  - Is there a relationship between body mass index and diabetic retinopathy in type
      II diabetic patients? A cross sectional study.
AB  - Background: Type 2 diabetes mellitus (T2DM) is one of the most important leading
      causes of disability, premature mortality and Diabetic Retinopathy (DR) that is
      one of the diabetes-related complications in diabetic patients and the most
      common cause of vision loss in diabetic patients. The aim of the study was to
      evaluate the association between DR and body mass index (BMI) in those patients
      with T2DM. Methods: This was a central-based, cross-sectional study on 518
      diabetic patients. Their medical history and the laboratory data were collected.
      All the patients received examination of diabetic retinopathy by professional
      ophthalmologist. Based on their optic fundi findings, they were classified into
      five groups: No retinopathy, Mild Non-proliferative Diabetic Retinopathy (NPDR),
      Moderate NPDR, Severe NPDR, Proliferative diabetic retinopathy (PDR). To analysis
      data SPSS v18 software used. Frequency, percent, mean and standard deviation were
      used for population description. t test, spearman correlation, partial
      correlation, analysis of variance (ANOVA) and Chi-square test (chi2) were used
      for analytic analysis. Multivariate logistic regression was used to estimate the
      odds ratio. Results: 518 patients with T2DM 198 male (38%), 320 female (62%)
      included in this study. The mean age of patients was 61.02 +/- 10.18 years. The
      mean age at onset was 49.06 + 10.52 years and the mean duration of diabetes was
      12.09 +/- 7.81 years. There was a strong relationship between duration of
      diabetes and DR (P = 0.001). There were strong significant association between
      the development of DR and Insulin therapy (OR = 5.975). Correlation analysis
      between Retinopathy and BMI showed that BMI had inverse relationship with DR when
      BMI considered as a continuous variable (p-value = 0.009 and correlation
      coefficient = -0.467). Conclusion: BMI in diabetic patient is one of the most
      important clinical parameter for their health and disease progression. We
      conclude that BMI had inverse relationship with DR when BMI considered as a
      continuous variable.

PMID- 30288387
TI  - Association of serum uric acid with nephropathy in Iranian type 2 diabetic
      patients.
AB  - Background: Diabetic nephropathy (DN) is the major cause of end-stage renal
      disease. Recent studies suggest that it is probable that uric acid is involved in
      the pathogenesis of diabetic nephropathy. This study aim was to investigate the
      association between serum uric acid and kidney function in Iranian patients with
      type 2 diabetes mellitus. Methods: In this case-control study, a total of 201
      diabetic patients with or without impaired kidney function (glomerular filtration
      rate/GFR < 60 and GFR >= 60) were selected. In both groups, serum fasting glucose
      (FBS), HbA1c, urea, creatinine, uric acid and lipid profile, urine albumin and
      GFR were measured and results were compared between the two groups. The results
      also categorized into three groups based on uric acid tertiles. Results: Serum
      levels of uric acid, urea and creatinine as well as urine albumin/creatinine
      ratio (ACR) were significantly different between the two groups. GFR, creatinine
      and also urea were significantly different between uric acid tertiles (p < 0.05).
      Conclusions: Serum uric acid is associated with decreased GFR as well as
      albuminuria and can be used as an indicator of DN.

PMID- 30288388
TI  - TLR4/MyD88 -mediated CCL2 production by lipopolysaccharide (endotoxin):
      Implications for metabolic inflammation.
AB  - Background: Obese human and mice were reported to have higher circularity
      endotoxin (LPS) levels as compared to their lean counter parts. The current study
      was aimed to reveal the molecular mechanisms underlying the LPS mediated
      induction of CCL2 in human monocytes/macrophages. Methods: Human monocytic cell
      line THP-1, THP-1 cells derived macrophages and primary macrophages were treated
      with LPS and TNF-alpha (positive control). CCL2 expression was determined with
      real-time RT-PCR and ELISA. THP-1-XBlueTM cells, THP-1-XBlueTM-defMyD cells, TLR4
      neutralization antibody, TLR4 siRNA and inhibitors for NF-kB and MAPK were used
      to study the signaling pathways. Phosphorylation of NF-kB and c-Jun was analyzed
      by ELISA. Results: LPS upregulates CCL2 expression at both mRNA (THP-1: 23.40 +/-
      .071 Fold, P < 0.0001; THP-1-derived macrophages: 103 +/- 0.56 Fold, < 0.0001;
      Primary macrophages: 48 +/- 1.41 Fold, P < 0.0005) and protein (THP1
      monocytes:1048 +/- 5.67 pg/ml, P < 0.0001; THP-1-derived macrophages; 2014 +/-
      2.12, P = 0.0001; Primary macrophages: 859.5 +/- 3.54, P < 0.0001) levels in
      human monocytic cells/macrophages. Neutralization of TLR4 blocked LPS-induced CCL
      2 secretion (P < 0.0001). Silencing of TLR4 by siRNA also significantly reduced
      LPS-induced CCL-2 production. Furthermore, MyD88-Knockout cells treated with LPS
      did not produce CCL-2. NF-kB and c-Jun phosphorylation was noted in LPS treated
      cells. Conclusion: Overall, our data reveal that LPS induces CCL-2 in
      monocytes/macrophages via TLR4/MyD88 signaling which leads to the activation of
      NF-kB/AP-1 transcription factors.

PMID- 30288390
TI  - Operative Treatment of Proximal Rectus Femoris Injuries in Professional Soccer
      Players: A Series of 19 Cases.
AB  - Background: Proximal rectus femoris (PRF) tears are relatively rare injuries
      among top-level athletes. PRF injuries can be avulsions of both tendon heads
      (direct and reflected heads) or of a single head, and some have a tendency to
      progress to recurrent injuries. Purpose: To describe a series of operatively
      treated PRF ruptures in professional soccer players. Study Design: Case series;
      Level of evidence, 4. Methods: Nineteen cases of PRF injuries (18 patients, 1
      bilateral) in professional soccer players who were treated surgically were
      retrospectively reviewed. Perioperative findings with return-to-play data were
      recorded. Results: Of the PRF injuries, 10 total avulsions (both heads) and 9
      single-head tears were seen on magnetic resonance imaging and were later
      confirmed during surgery. All 18 patients returned to their preinjury level of
      play (mean follow-up, 2.8 years [range, 1-11 years]). Conclusion: The repair of
      PRF tears in professional soccer players yielded good results and allowed all
      patients to return to their preinjury level of play.

PMID- 30288389
TI  - Colony-stimulating factors detected in tumor cells and voided urine are potential
      prognostic markers for patients with muscle-invasive bladder cancer undergoing
      radical cystectomy.
AB  - Background: The clinical use of macrophage colony-stimulating factor, granulocyte
      colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating
      factor (GM-CSF) has improved the safety of cytotoxic chemotherapy. However, the
      overexpression of these CSFs in cancers has been reported to be associated with a
      poor prognosis in various malignancies. We evaluated the potential of CSF
      expression as a predictor of clinical outcome in patients with muscle-invasive
      bladder cancer (MIBC). Methods: Consecutive patients (n=58) with MIBC who
      underwent radical cystectomy (RC) were included in this retrospective study.
      Treatment-naive tumor specimens obtained by initial transurethral resection of
      bladder tumors prior to RC were immunostained with antibodies against macrophage
      colony-stimulating factor, G-CSF, and GM-CSF. We compared the clinicopathological
      variables and survival between these groups. Baseline levels of CSFs in the serum
      and voided urine were quantified using an enzyme-linked immunosorbent assay and
      compared with the expression of CSFs in the tumor lesions. Results: Low
      expression of GM-CSF in the tumor cells was significantly correlated with a
      pathological T4 category (vs T2-3; P=0.02). In univariate survival analysis, high
      G-CSF and low GM-CSF expression in the tumor lesion were associated with poor
      outcomes. Furthermore, Cox proportional regression analysis revealed that high G
      CSF and low GM-CSF expression in the tumor were independent predictors of shorter
      recurrence-free survival, cancer-specific survival, and overall survival. The
      levels of CSFs in voided urine were associated with the expression of CSFs in the
      tumor lesions. Conclusion: GM-CSF and G-CSF expression in the tumor lesions
      obtained by initial transurethral resection are independent predictors of poor
      outcome in MIBC after RC. Levels of G-CSF and GM-CSF in urine before treatment
      could be useful in prognostication.

PMID- 30288391
TI  - Athletic Hip Injuries in Major League Baseball Pitchers Associated With Ulnar
      Collateral Ligament Tears.
AB  - Background: Ulnar collateral ligament (UCL) reconstruction is a reliable
      treatment for elite overhand throwers with UCL tears. In recent years, this
      procedure has become increasingly common among Major League Baseball (MLB)
      pitchers. Predisposing factors and associated comorbidities, however, have not
      been fully elucidated. Purpose/Hypothesis: The purpose of this study was to
      determine whether professional baseball pitchers who underwent UCL reconstruction
      had an increased incidence of hip or groin injuries 4 years before or after
      surgery. We hypothesized that MLB pitchers who sustain hip or groin injuries may
      be more likely to develop UCL tears because of alterations and overcompensation
      in the kinetic chain during overhand throwing. Study Design: Cohort study; Level
      of evidence, 3. Methods: A comprehensive list of all 247 MLB players who
      underwent UCL reconstruction between 2005 and 2017 was created using publicly
      accessible online data. The application of inclusion criteria yielded a final
      sample size of 145 athletes. These athletes' injury histories were identified and
      cross-referenced with the official MLB disabled list. Matched controls were
      generated for a comparison of results. Results: Of the 145 MLB pitchers who
      underwent UCL reconstruction between 2005 and 2017, 40 (27.6%) endured a proximal
      lower extremity injury within 4 years of their surgery. Specifically, 16 pitchers
      sustained hip injuries, 13 suffered hamstring injuries, and 14 experienced groin
      injuries. A significantly lower rate of hip- and groin-related injuries (17.9%)
      was identified in matched controls during a similar time frame (P = .049).
      Conclusion: The results of this study demonstrate that MLB pitchers who required
      UCL reconstruction sustained a higher frequency of proximal lower extremity
      injuries both before and after surgery compared with matched controls. This
      finding is significant as the treatment of antecedent hip lesions, as well as an
      emphasis on hip and core muscle mobility and strengthening, may help reduce
      injuries to the UCL.

PMID- 30288392
TI  - Using a Positive Deviance Approach to Influence the Culture of Patient Safety
      Related to Infection Prevention.
AB  - Background: Health care-associated infections (HAIs) are a socio-technical
      problem. We evaluated the impact of a social change intervention on health care
      personnel (HCP), called "positive deviance" (PD), on patient safety culture
      related to infection prevention among HCP. Methods: This observational study was
      done in 6 medical wards at an 800-bed public academic hospital in the United
      States. Three of these wards were randomly assigned to receive PD intervention on
      HCP. After a retrospective 6-month baseline period, PD was implemented over 9
      months, followed by 9 months of follow-up. Patient safety culture and social
      networks among HCP were surveyed at 6, 15, and 24 months. Rates of HAI were
      measured among patients. Results: The measured patient safety culture was steady
      over time at 69% aggregate percent positive responses in wards with PD vs decline
      from 79% to 75% in wards without PD (F statistic 10.55; P = .005). Social network
      maps suggested that nurses, charge nurses, medical assistants, ward managers, and
      ward clerks play a key role in preventing infections. Fitted time series of
      monthly HAI rates showed a decrease from 4.8 to 2.8 per 1000 patient-days (95%
      confidence interval [CI], 2.1 to 3.5) in wards without PD, and 5.0 to 2.1 per
      1000 patient-days (95% CI, -0.4 to 4.5) in wards with PD. Conclusions: A positive
      deviance approach appeared to have a significant impact on patient safety culture
      among HCP who received the intervention. Social network analysis identified HCP
      who are likely to help disseminate infection prevention information. Systemwide
      interventions independent of PD resulted in HAI reduction in both intervention
      and control wards.

PMID- 30288394
TI  - Newborn With Enlarged Erythematous Mass on Back: Case Report and Review of
      Medical Literature.
AB  - Newborn skin nodules are usually benign and self-resolving skin condition.
      Differential diagnosis of such lesions include cysts, hemangioma, abscess,
      cellulitis, sclerema neonatorum, subcutaneous fat necrosis, neurofibromatosis,
      benign tumors, or malignant tumors such as rhabdomyosarcoma, infantile
      fibrosarcoma, or neuroblastoma. We report a case of congenital subcutaneous fat
      necrosis in a 7-day-old baby presenting with multiple erythematous mass on back.

PMID- 30288393
TI  - Intensive Combination Immunotherapy and Neuroinflammation Resolution in a Child
      With Anti-PCA-1 (Yo) Paraneoplastic Syndrome and 2 Malignancies.
AB  - Paraneoplastic cerebellar degeneration is rare and noteworthy in children. In
      this 7-year-old, it was documented to have occurred within a year of ataxia
      presentation. The instigating cancer was stage III adrenal adenocarcinoma,
      remitted after surgical resection at age 2. When her severe ataxia progressed,
      neuroinflammation was characterized by high cerebrospinal fluid Purkinje cell
      cytoplasmic antibody type 1 titers, oligoclonal bands, and neurofilament light
      chain. The immunotherapy strategy was to replace IV methylprednisolone, which
      lowered Purkinje cell cytoplasmic antibody type 1 titers without clinical
      improvement, with induction of adrenocorticotropic hormone/intravenous
      immunoglobulin/rituximab (ACTH/IVIG/rituximab) combination immunotherapy,
      ACTH/dexamethasone transition, and intravenous immunoglobulin maintenance. She
      became self-ambulatory and cerebrospinal fluid inflammatory markers regressed.
      Down syndrome predisposed her to a second cancer, pre-B acute lymphoblastic
      leukemia, 4 years later. Despite reversible cytosine arabinoside-provoked
      cerebellar toxicity, the ataxia is stable on monthly intravenous immunoglobulin
      without relapse, now 5 years after initial diagnosis. This report illustrates the
      use of cerebrospinal fluid biomarkers to detect, target, and monitor
      neuroinflammation, and successful combinations of immunotherapy to better the
      quality of life.

PMID- 30288395
TI  - Effective Formats for Communicating Risks from Cigarette Smoke Chemicals.
AB  - Objective: The US government requires the public display of information about
      toxic chemicals in cigarettes and smoke by brand in a way that is understandable
      and not misleading. We sought to identify risk communication formats that meet
      these goals. Methods: We conducted 3 online experiments with US adult convenience
      samples (total N = 1866). Participants viewed a webpage displaying information
      about chemicals in the smoke of a cigarette brand. Experiment 1 varied the
      chemicals listed and format for their health effects. Experiments 2 and 3 varied
      the format of chemical quantities and presence/absence of a visual risk
      indicator. Outcomes were understandable (increasing knowledge) and not misleading
      (not reinforcing misperceptions). Results: Information about chemicals and health
      effects increased knowledge of these topics by ~30% (p < .001) compared to no
      information. Quantity format and use of a risk indicator generally did not affect
      knowledge. The proportion of participants misled ranged from 0% to 92%, depending
      on measure. Findings indicated 52% would use a website to search for safer
      cigarettes. Risk communication formats did little to reduce being misled.
      Conclusions: Some risk communication formats successfully increased knowledge of
      chemicals and health effects. However, the formats did little to reduce the
      proportion of people misled.

PMID- 30288396
TI  - Localized SDF-1alpha Delivery Increases Pro-Healing Bone Marrow-Derived Cells in
      the Supraspinatus Muscle Following Severe Rotator Cuff Injury.
AB  - To examine how the chemotactic agent stromal cell-derived factor-1alpha (SDF
      1alpha) modulates the unique cellular milieu within rotator cuff muscle following
      tendon injury, we developed an injectable, heparin-based microparticle platform
      to locally present SDF-1alpha within the supraspinatus muscle following severe
      rotator cuff injury. SDF-1alpha loaded, degradable, N-desulfated heparin-based
      microparticles were fabricated, injected into a rat model of severe rotator cuff
      injury, and were retained for up to 7 days at the site. The resultant
      inflammatory cell and mesenchymal stem cell populations were analyzed compared to
      uninjured contralateral controls and, after 7 days, the fold-change in anti
      inflammatory, M2-like macrophages (CD11b+CD68+CD163+, 4.3X fold-change) and
      mesenchymal stem cells (CD29+CD44+CD90+, 3.0X, respectively) was significantly
      greater in muscles treated with SDF-1alpha loaded microparticles than unloaded
      microparticles or injury alone. Our results indicate that SDF-1alpha loaded
      microparticles may be a novel approach to shift the cellular composition within
      the supraspinatus muscle and create a more pro-regenerative milieu, which may
      provide a platform to improve muscle repair following rotator cuff injury in the
      future.

PMID- 30288397
TI  - The Great Recession and Immune Function.
AB  - The Great Recession precipitated unprecedented home foreclosures increases, but
      documentation of related neighborhood changes and population health is scant.
      Using the Detroit Neighborhood Health Study (N = 277), we examined associations
      between neighborhood-level recession indicators and thymic function, a life
      course immunological health indicator. In covariate-adjusted multilevel models,
      each 10 percentage point increase in abandoned home prevalence and 1 percentage
      point increase in 2009 home foreclosures was associated with 1.7-year and 3.3
      year increases in thymic aging, respectively. Associations attenuated after
      adjustment for neighborhood-level social cohesion, suggesting community ties may
      buffer recession-related immune aging. Effects of neighborhood stressors were
      strongest in middle-income households, supporting theory of excess vulnerability
      in this group. Future research should assess whether ongoing foreclosure and
      blight reduction efforts improve health for residents of recession impacted
      neighborhoods.

PMID- 30288398
TI  - Synthetic Cathinones: A Brief Overview of Overviews with Applications to the
      Forensic Sciences.
AB  - Catha edulis, the fresh leaves of which (i.e., khat) are used for their central
      stimulant actions, has been known for many hundreds of years. S(-)Cathinone was
      identified as a centrally-active khat constituents >30 years ago. Although khat
      use was a problem long localized to certain Middle Eastern and certain Eastern
      African nations, 'synthetic cathinones' (synthetic analogs of cathinone)
      represent a "new" class of abused substances with growing worldwide appeal. To
      date, about 150 synthetic cathinones have been identified on the clandestine
      market, and only a dozen or so have been controlled (U.S. Schedule I). Because
      these agents do not represent a pharmacologically (i.e., behavioral) or
      mechanistically homogeneous class of agents, synthetic cathinones are being
      investigated one agent at a time to understand their actions, mechanisms of
      action, metabolism, toxicity, and abuse potential - the latter to identify
      possible modes of overdose treatment and for Scheduling purposes. The available
      agents might represent only the 'tip of the iceberg'; the potential for many more
      new synthetic cathinones is very real. Investigation of these agents on an agent
      by-agent basis is a daunting task. Attempts are being made to understand these
      agents as a class, by examination of their structure-activity relationships.
      Here, we provide an overview of review articles that attempts to shed light on
      these agents as a class, rather than on an agent-by-agent basis. This article is
      meant to be a reference resource that might expedite the work of those in this
      field by directing them to where they can find useful information.

PMID- 30288399
TI  - Is Shared Decision Making for End-of-Life Decisions Associated With Better
      Outcomes as Compared to Other Forms of Decision Making? A Systematic Literature
      Review.
AB  - Background: Whether shared decision making (SDM) has been evaluated for end-of
      life (EOL) decisions as compared to other forms of decision making has not been
      studied. Purpose: To summarize the evidence on SDM being associated with better
      outcomes for EOL decision making, as compared to other forms of decision making.
      Data Sources: PubMed, Web of Science, Cochrane Central Register of Controlled
      Trials, EMBASE, PsycINFO, and CINAHL databases were searched through April 2014.
      Study Selection: Studies were selected that evaluated SDM, compared to any other
      decision making style, for an EOL decision. Data Extraction: Components of SDM
      tested, comparators to SDM, EOL decision being assessed, and outcomes measured.
      Data Synthesis: Seven studies met the inclusion criteria (three experimental and
      four observational studies). Results were analyzed using narrative synthesis. All
      three experimental studies compared SDM interventions to usual care. The four
      observational studies compared SDM to doctor-controlled decision making, or
      reported the correlation between level of SDM and outcomes. Components of SDM
      specified in each study differed widely, but the component most frequently
      included was presenting information on the risks/benefits of treatment choices
      (five of seven studies). The outcome most frequently measured was communication,
      although with different measurement tools. Other outcomes included decisional
      conflict, trust, satisfaction, and "quality of dying." Limitations: We could not
      analyze the strength of evidence for a given outcome due to heterogeneity in the
      outcomes reported and measurement tools. Conclusions: There is insufficient
      evidence supporting SDM being associated with improved outcomes for EOL decisions
      as opposed to other forms of decision making. Future studies should describe
      which components of SDM are being tested, outline the comparator decision making
      style, and use validated tools to measure outcomes.

PMID- 30288400
TI  - Value of Information Analysis Informing Adoption and Research Decisions in a
      Portfolio of Health Care Interventions.
AB  - Background: Value of information (VOI) analysis quantifies the value of
      additional research in reducing decision uncertainty. It addresses adoption and
      research decisions simultaneously by comparing the expected benefits and costs of
      research studies. Nevertheless, the application of this approach in practice
      remains limited. Objectives: To apply VOI analysis in health care interventions
      to guide adoption decisions, optimize trial design, and prioritize research.
      Methods: The analysis was from the perspective of Queensland Health, Australia.
      It included four interventions: clinically indicated catheter replacement, tissue
      adhesive for securing catheters, negative pressure wound therapy (NPWT) in
      caesarean sections, and nutritional support for preventing pressure ulcers. For
      each intervention, cost-effectiveness analysis was performed, decision
      uncertainty characterized, and VOI calculated using Monte Carlo simulations. The
      benefits and costs of additional research were considered together with the costs
      and consequences of acting now versus waiting for more information. All values
      are reported in 2014 Australian dollars (AU$). Results: All interventions were
      cost-effective, but with various levels of decision uncertainty. The current
      evidence is sufficient to support the adoption of clinically indicated catheter
      replacement. For the tissue adhesive, an additional study before adoption is
      worthwhile with a four-arm trial of 220 patients per arm. Additional research on
      NPWT before adoption is worthwhile with a two-arm trial of 200 patients per arm.
      Nutritional support should be adopted with a two-arm trial of 1200 patients per
      arm. Based on the expected net monetary benefits, the studies were ranked as
      follows: 1) NPWT (AU$1.2 million), 2) tissue adhesive (AU$0.3 milliion), and 3)
      nutritional support (AU$0.1 million). Conclusions: VOI analysis is a useful and
      practical approach to inform adoption and research decisions. Efforts should be
      focused on facilitating its integration into decision making frameworks.

PMID- 30288401
TI  - Blood Pressure Control in Hypertensive Patients in Federally Qualified Health
      Centers: Impact of Shared Decision Making in the Office-GAP Program.
AB  - : Background: Hypertension (HTN) in people with diabetes doubles the risk of
      cardiovascular disease. Prior patient activation studies largely show improved
      communication but little impact on behavior or health outcomes. We sought to 1)
      assess the impact of Office-Based Guidelines Applied to Practice (Office-GAP)
      Program on blood pressure (BP) control; 2) determine the rate and predictors of
      BP control in patients with HTN and/or diabetes mellitus (DM) in federally
      qualified health centers. Methods: Sample: Patients with coronary heart disease
      (CHD) and/or DM with history of HTN; analyzed patients with DM and HTN compared
      to HTN without DM. INTERVENTION: Office-GAP included physician training, patient
      activation, and an Office-GAP decision checklist. Two-site intervention/control
      design; data collection at baseline and after 3, 6, and 12 months. Logistic
      regression with propensity scoring assessed impact on BP control over time.
      Results: Of 243 patients, HTN was present in 75% at baseline; 32% had BP
      controlled. Consistent trend showed Office-GAP slightly improved the rate of BP
      control across time, while the control arm showed a nonsignificant decrease in
      the rate of BP control across time, compared to baseline. BP improved at 6 months
      at the intervention site compared to control site (odds ratio = 2.92; 95%
      confidence interval = 1.11-7.69). Conclusion: BP control was better at the
      intervention site compared to the control site at 6 months. Office-GAP shows
      promise to implement guidelines-based patient-centered care that improves BP.

PMID- 30288402
TI  - Developing and Evaluating a Clinic-Based Decision Aid Delivery System.
AB  - Background: Despite evidence of their benefits, decision aids (DAs) have not been
      widely adopted in clinical practice. Quality improvement methods could help embed
      DA delivery into primary care workflows and facilitate DA delivery and uptake,
      defined as reading or watching DA materials. Objectives: 1) Work with clinic
      staff and providers to develop and test multiple processes for DA delivery; 2)
      implement a systems approach to measuring delivery and uptake; 3) compare uptake
      and patient satisfaction across delivery models. Methods: We employed a
      microsystems approach to implement three DA delivery models into primary care
      processes and workflows: within existing disease management programs, by
      physician request, and by mail. We developed a database and tracking tools linked
      to our electronic health record and designed clinic-based processes to measure
      uptake and satisfaction. Results: A total of 1144 DAs were delivered. Depending
      on delivery method, 51% to 73% of patients returned to the clinic within 6
      months. Nurses asked 67% to 75% of this group follow-up questions, and 65% to 79%
      recalled receiving the DA. Among them, uptake was 23% to 27%. Satisfaction among
      patients who recalled receiving the DA was high. Eighty-two to 93% of patients
      reported that they liked receiving this patient education information, and 82% to
      91% reported that receiving patient education information like this is useful to
      them. Conclusion: Our results demonstrate the realities of clinical practice. One
      fourth to one third of patients did not return for a follow-up visit. Although
      nurses were able to assess uptake in the course of their usual duties, the
      results did not achieve the standards typically expected of clinical research.
      Despite these limitations, uptake, though modest, was similar across delivery
      methods, suggesting that there are multiple strategies for implementing DAs in
      clinical practice.

PMID- 30288403
TI  - Barriers to and Facilitators of Evidence-Based Decision Making at the Point of
      Care: Implications for Delivery Systems, Payers, and Policy Makers.
AB  - Introduction: Physicians vary widely in how they treat some health conditions,
      despite strong evidence favoring certain treatments over others. We examined
      physicians' perspectives on factors that support or hinder evidence-based
      decisions and the implications for delivery systems, payers, and policymakers.
      Methods: We used Choosing Wisely(r) recommendations to create four clinical
      vignettes for common types of decisions. We conducted semi-structured interviews
      with 36 specialists to identify factors that support or hinder evidence-based
      decisions. We examined these factors using a conceptual framework that includes
      six levels: patients, physicians, practice sites, organizations, networks and
      hospital affiliations, and the local market. In this model, population
      characteristics and payer and regulatory factors interact to influence decisions.
      Results: Patient openness to behavior modification and expectations, facilitated
      and hindered physicians in making evidence-based recommendations. Physicians'
      communication skills were the most commonly mentioned facilitator. Practice site,
      organization, and hospital system barriers included measures of emergency
      department throughput, the order in which test options are listed in electronic
      health records (EHR), lack of relevant decision support in EHRs, and payment
      incentives that maximize billing and encourage procedures rather than medical
      management or counseling patients on behavior change. Factors from different
      levels interacted to undermine evidence-based care. Most physicians received
      billing feedback, but quality metrics on evidence-based service use were
      nonexistent for the four decisions in this study. Conclusions and Implications:
      Additional research and quality improvement may help to modify delivery systems
      to overcome barriers at multiple levels. Enhancing provider communication skills,
      improving decision support in EHRs, modifying workflows, and refining the design
      and interpretation of some quality metrics would help, particularly if combined
      with concurrent payment reform to realign financial incentives across
      stakeholders.

PMID- 30288404
TI  - Introducing MDM Policy & Practice.

PMID- 30288405
TI  - A Simple Tool for Communicating the Benefits and Harms of Health Interventions: A
      Guide for Creating a Fact Box.
AB  - One of the major hurdles to promoting informed decision making in health is the
      continued use of poor risk presentation formats. This article offers a guide to
      develop a Fact Box, a simple decision tool to present data about the benefits and
      harms of treatments that has been demonstrated to improve understanding of health
      risks, an important part of risk literacy. The article offers guidance about how
      to determine the evidence basis for a health topic, select outcomes to report,
      extract and present numbers or outcomes, and design the layout. The guide also
      addresses potential challenges for summarizing evidence and provides alternatives
      for addressing issues related to missing, insufficient, imprecise, or conflicting
      evidence and for dealing with issues related to statistical and clinical
      significance. The guide concludes with details on how to document the development
      of the Fact Box for the purpose of transparency and reproducibility. Fact Boxes
      are an efficient tool to promote risk literacy and should be available in every
      physician's office.

PMID- 30288406
TI  - Lay Judgments of Mental Health Treatment Options: The Mind Versus Body Problem.
AB  - Background: Past research shows that people believe psychologically caused mental
      disorders are helped by different treatments than biologically caused mental
      disorders. However, it is unknown how people think about treatment when limited
      information is known to identify the disorder. Objective: Our objective was to
      explore how laypeople judged the helpfulness of treatments when a limited set of
      mental health symptoms is presented. Method: Across four experiments, Mechanical
      Turk and college undergraduate participants (N = 331) read descriptions
      displaying sets of three mental health symptoms and rated how helpful
      pharmaceuticals, counseling, or alternative medicine would be on a 0 (not at all
      helpful) to 100 (completely helpful) scale. We measured judgments for perceived
      mental and medical symptoms (Experiment 1) and how judgments were influenced by
      symptom severity (Experiment 2), duration (Experiment 3), and if alternative
      medicine and conventional treatments were used in conjunction (Experiment 4).
      Results: Perceived mental symptoms were rated as helped by counseling, while
      perceived medical symptoms were rated as helped by medication. Alternative
      medicine was never rated as extremely helpful. For example, in Experiment 1,
      counseling (mean [M] = 80.1) was rated more helpful than pharmaceuticals (M =
      50.5; P < 0.001) or alternative medicine (M = 45.1; P < 0.001) for mental
      symptoms, and pharmaceuticals (M = 62.6) was rated more helpful than counseling
      (M = 36.1; P < 0.001) or alternative medicine (M = 47.5; P < 0.001) for medical
      symptoms. This pattern held regardless of severity, duration, or the adjunct use
      of alternative medicine. Limitations: We employed a general population sample and
      measured hypothetical treatment judgments. Conclusions: Mental health symptoms
      viewed as problems of the mind are thought to need different treatment than
      mental health symptoms seen as problems of the body.

PMID- 30288407
TI  - Do Economic Evaluations in Primary Care Prevention and the Management of
      Hypertension Conform to Good Practice Guidelines? A Systematic Review.
AB  - Background: Results of previous research have identified the need for further
      investigation into the compliance with good practice guidelines for current
      decision-analytic modeling (DAM). Objective: To identify the extent to which
      recent model-based economic evaluations of interventions focused on lowering the
      blood pressure (BP) of patients with hypertension conform to published guidelines
      for DAM in health care using a five-dimension framework developed to assess
      compliance to DAM guidelines. Methods: A systematic review of English language
      articles was undertaken to identify published model-based economic evaluations
      that examined interventions aimed at lowering BP. The review covered the period
      January 2000 to March 2015 and included the following electronic bibliographic
      databases: EMBASE and Medline via Ovid interface and the Centre for Reviews and
      Dissemination's (CRD) NHS-EED. Data were extracted based on different components
      of good practice across five dimensions utilizing a framework to assess
      compliance to DAM guidelines. Results: Thirteen articles were included in this
      review. The review found limited compliance to good practice DAM guidelines,
      which was most frequently justified by the lack of data. Conclusions: The
      assessment of structural uncertainty cannot yet be considered common practice in
      primary prevention and management of hypertension, and researchers seem to face
      difficulties with identifying sources of structural uncertainty and then handling
      them correctly. Additional guidelines are needed to aid researchers in
      identifying and managing sources of potential structural uncertainty. Adherence
      to guidelines is not always possible and it does pose challenges, in particular
      when there are limitations due to data availability that restrict, for example, a
      validation process.

PMID- 30288408
TI  - Impact of the "Linked Evidence Approach" Method on Policies to Publicly Fund
      Diagnostic, Staging, and Screening Medical Tests.
AB  - Background: The linked evidence approach (LEA) is used in health technology
      assessment (HTA) to evaluate the clinical utility of new medical tests in the
      absence of direct trial evidence. Objective: To determine whether use of LEA
      affects decisions to publicly fund medical tests. Methods: Australian HTAs that
      evaluated medical tests before and after LEA was mandated (in 2005) were screened
      for eligibility. Data were extracted and the impact of LEA and other possible
      clinical predictors (selected a priori) on funding decisions was modelled.
      Regression diagnostics were performed to estimate model fit, model specification,
      and to inform model selection. The unit of analysis was per clinical indication
      for each new test, so analyses were adjusted for clustering. Results: 83 HTAs
      (for 173 clinical indications) were eligible from the 259 screened. When health
      policy was compared before and after 2005, there was an 11% reduction in overall
      positive funding decisions, including a 25% decrease in "interim" (coverage with
      evidence development) funding decisions. The odds of obtaining interim funding
      reduced by 98% (odds ratio = 0.02, 95% confidence interval = 0.0005, 0.17), but
      there was no change in the direction of funding decisions (odds ratio = 1.36, 95%
      confidence interval = 0.62, 3.01). Across both time periods, when LEA was used
      there was a very strong likelihood that the medical test would not receive
      interim funding (chi2 = 12.63, df = 1, P = 0.001). For positive funding
      decisions, the strongest predictors were whether or not the new test would
      replace an existing test and whether the available evidence was limited.
      Conclusions: The use of LEA did not predict the direction of funding decisions.
      Application of the method did predict that a "coverage with evidence development"
      decision was unlikely. This suggests that LEA may reduce decision-maker
      uncertainty.

PMID- 30288409
TI  - Data-Driven Markov Decision Process Approximations for Personalized Hypertension
      Treatment Planning.
AB  - Background: Markov decision process (MDP) models are powerful tools. They enable
      the derivation of optimal treatment policies but may incur long computational
      times and generate decision rules that are challenging to interpret by
      physicians. Methods: In an effort to improve usability and interpretability, we
      examined whether Poisson regression can approximate optimal hypertension
      treatment policies derived by an MDP for maximizing a patient's expected
      discounted quality-adjusted life years. Results: We found that our Poisson
      approximation to the optimal treatment policy matched the optimal policy in 99%
      of cases. This high accuracy translates to nearly identical health outcomes for
      patients. Furthermore, the Poisson approximation results in 104 additional
      quality-adjusted life years per 1000 patients compared to the Seventh Joint
      National Committee's treatment guidelines for hypertension. The comparative
      health performance of the Poisson approximation was robust to the cardiovascular
      disease risk calculator used and calculator calibration error. Limitations: Our
      results are based on Markov chain modeling. Conclusions: Poisson model
      approximation for blood pressure treatment planning has high fidelity to optimal
      MDP treatment policies, which can improve usability and enhance transparency of
      more personalized treatment policies.

PMID- 30288410
TI  - Computer-assisted Medical Decision-making System for Diagnosis of Urticaria.
AB  - Background: Urticaria is a common allergic disease that affects all age groups.
      Allergic disorders are diagnosed at allergy testing centers using skin tests.
      Though skin tests are the gold standard tests for allergy diagnosis, specialists
      are required to interpret the observations and test results. Hence, a computer
      assisted medical decision-making (CMD) system can be used as an aid for decision
      support, by junior clinicians, in order to diagnose the presence of urticaria.
      Methods: The data from intradermal skin test results of 778 patients, who
      exhibited allergic symptoms, are considered for this study. Based on food habits
      and the history of a patient, 40 relevant allergens are tested. Allergen extracts
      are used for skin test. Ten independent runs of 10-fold cross-validation are used
      to train the system. The performance of the CMD system is evaluated using a set
      of test samples. The test samples were also presented to the junior clinicians at
      the allergy testing center to diagnose the presence or absence of urticaria.
      Results: From a set of 91 features, a subset of 41 relevant features is chosen
      based on the relevance score of the feature selection algorithm. The Bayes
      classification approach achieves a classification accuracy of 96.92% over the
      test samples. The junior clinicians were able to classify the test samples with
      an average accuracy of 75.68%. Conclusion: A probabilistic classification
      approach is used for identifying the presence or absence of urticaria based on
      intradermal skin test results. In the absence of an allergy specialist, the CDM
      system assists junior clinicians in clinical decision making.

PMID- 30288411
TI  - How Do Psychiatrists Apply the Minimum Clinically Important Difference to Assess
      Patient Responses to Treatment?
AB  - Symptom report scales are used in clinical practice to monitor patient outcomes.
      Using them permits the definition of a minimum clinically important difference
      (MCID) beyond which a patient may be judged as having responded to treatment.
      Despite recommendations that clinicians routinely use MCIDs in clinical practice,
      statisticians disagree about how MCIDs should be used to evaluate individual
      patient outcomes and responses to treatment. To address this issue, we asked how
      clinicians actually use MCIDs to evaluate patient outcomes in response to
      treatment. Sixty-eight psychiatrists made judgments about whether hypothetical
      patients had responded to treatment based on their pre- and posttreatment change
      scores on the widely used Positive and Negative Syndrome Scale. Psychiatrists
      were provided with the scale's MCID on which to base their judgments. Our
      secondary objective was to assess whether knowledge of the patient's genotype
      influenced psychiatrists' responder judgments. Thus, psychiatrists were also
      informed of whether patients possessed a genotype indicating hyperresponsiveness
      to treatment. While many psychiatrists appropriately used the MCID, others
      accepted a far lower posttreatment change as indicative of a response to
      treatment. When psychiatrists accepted a lower posttreatment change than the
      MCID, they were less confident in such judgments compared to when a patient's
      posttreatment change exceeded the scale's MCID. Psychiatrists were also less
      likely to identify patients as responders to treatment if they possessed a
      hyperresponsiveness genotype. Clinicians should recognize that when judging
      patient responses to treatment, they often tolerate lower response thresholds
      than warranted. At least some conflate their judgments with information, such as
      the patient's genotype, that is irrelevant to a post hoc response-to-treatment
      assessment. Consequently, clinicians may be at risk of persisting with treatments
      that have failed to demonstrate patient benefits.

PMID- 30288412
TI  - Patient and Provider Perspectives on Mammographic Breast Density Notification
      Legislation.
AB  - Background: Patient advocacy has fostered the implementation of mammographic
      breast density (MBD) notification legislation in many states. Little is known
      about the perspectives of women, primary care physicians (PCPs), and breast
      radiologists in response to this legislation. The objective of this research was
      to elicit qualitative information from these multiple stakeholders to understand
      varied perspectives on the subject of MBD notification and inform best practices
      around implementation. Methods: Content analysis of narrative data from focus
      groups with women (2 groups, total of 16 participants) and in-depth interviews
      with PCPs (n = 7) and breast radiologists (n = 7). Results: Three major themes
      emerged from the data: 1) knowledge and general attitudes about legislation, 2)
      concerns about consequences, and 3) actions patients and clinicians should
      consider based on MBD information. For each of these themes, the views of women,
      PCPs, and radiologists often demonstrated different perspectives. Conclusion:
      This work supports the need for clear and concise tools for patients and
      providers to understand MBD in the context of a woman's overall breast cancer
      risk with guidance on next steps.

PMID- 30288413
TI  - What Factors Affect Physicians' Decisions to Prescribe Opioids in Emergency
      Departments?
AB  - Objective: With 42% of all emergency department visits in the United States
      related to pain, physicians who work in this setting are tasked with providing
      adequate pain management to patients with varying primary complaints and medical
      histories. Complicating this, the United States is in the midst of an opioid
      overdose epidemic. State governments and national organizations have developed
      guidelines and legislation to curtail opioid prescriptions in acute care
      settings, while also incentivizing providers for patient satisfaction and
      completeness of pain control. In order to inform future policies that focus on
      provider pain medication prescribing, we sought to characterize the factors
      physicians weigh when considering treating pain with opioids in the emergency
      department. Methods: We conducted and transcribed open-ended, semistructured
      qualitative interviews with 52 physicians at a national emergency medicine
      conference. Results: Participants reported a wide range of factors contributing
      to their opioid prescribing patterns related to three domains: 1) provider
      assessment of pain characteristics, 2) patient-based considerations, and 3)
      practice environment. Pain characteristics include the characteristics of various
      acute and chronic pain syndromes, including physicians' empathy due to their own
      experiences with pain. Patient characteristics include "trustworthiness," race
      and ethnicity, and the concern for risk of misuse. Factors related to the
      practice environment include hospital policy, legislation/regulation, and
      guidelines. Conclusion: The decision to prescribe opioids to patients in the
      emergency department is complex and nuanced. Physicians are interested in
      guidance and are concerned about the competing pressures placed on their opioid
      prescribing due to incentives related to patient satisfaction scores on one hand
      and inflexible policies that do not allow for individualized, patient-centered
      decisions on the other.

PMID- 30288414
TI  - Optimizing Implementation of Hepatitis C Birth-Cohort Screening and Treatment
      Strategies: Model-Based Projections.
AB  - Background: Chronic hepatitis C (HCV) is a significant public health problem
      affecting more than three million Americans. The US health care systems are
      ramping up costly HCV screening and treatment efforts with limited budget. We
      determine the optimal implementation of HCV birth-cohort screening and treatment
      strategies under budget constraints and health care payer's perspective. Methods:
      Markov model and scenario-based simulation optimization. The target population is
      birth cohort born between 1945 and 1975. The interventions are allocating annual
      budget to screen a proportion of the target population and treat a proportion of
      the identified chronic HCV-positive patients over 10 years. Outcomes measure is
      to maximize lifetime discounted quality-adjusted life-years. Results: Allocate a
      percentage of the annual budget to screening, then treat patients with the
      remaining budget and prioritize the sickest patients. When the budget is $1
      billion/year, the best strategy is to allocate the entire budget to treatment.
      When the budget is $5 billion/year, it is optimal to allocate 60% of the budget
      to screening in the first 2 years and 0% thereafter for age cohort 40 to 49; and
      allocate 20% of the budget to screening starting in year 3 for age cohorts 50 to
      59 and 60 to 69. Health benefits are sensitive to budget in the first 2 years.
      Results are not sensitive to distribution of fibrosis stages by awareness of HCV.
      Conclusion: When budget is limited, all efforts should be focused on early
      treatment. With higher budget, better population health outcomes are achieved by
      reserving some budget for HCV screening while implementing a priority-based
      treatment strategy. This work has broad applicability to diverse health care
      systems and helps determine how much effort should be devoted to screening versus
      treatment under resource limitations.

PMID- 30288415
TI  - Designing the Free Drugs List in Nepal: A Balancing Act Between Technical
      Strengths and Policy Processes.
AB  - As more countries provide free health care, pharmaceutical reimbursement lists
      are becoming a concern, especially in low- and middle-income countries. In 2007,
      Nepal decreed that health is a human right and began basic health coverage for a
      target group of the poor, destitute, elderly, and disabled. The Ministry of
      Health and Population (MoHP) also provided 40 drugs without cost to all citizens
      through the Free Drugs List (FDL) program. The FDL was later expanded from 40 to
      70 drugs; however, the process of review and update remains unclear. To propose a
      mechanism for future development of the FDL, we conducted a document review and
      in-depth consultations with representatives from the MoHP and the World Health
      Organization Country Office during a workshop in Kathmandu. The FDL suffers from
      lack of an appropriate process, gaps between the listed drugs and Nepal's burden
      of disease, and no consideration of the unit costs or cost-effectiveness of drugs
      included in the list. We propose a new drug selection process that is a variant
      of the health technology assessment process. This process can be applied not only
      in Nepal but also in other resource-limited countries that wish to ensure their
      citizens' access to essential medicines through a pharmaceutical reimbursement
      list.

PMID- 30288416
TI  - The External Validity of Mapping MSIS-29 on EQ-5D Among Individuals With Multiple
      Sclerosis in Sweden.
AB  - Background: Mapping can be performed to predict utility values from condition
      specific measures when preference-based measures are absent. A previously
      developed algorithm that predicts EQ-5D-3L index values from the Multiple
      Sclerosis Impact Scale (MSIS-29) has not yet been externally validated. Aim: To
      examine the external validity of a previously developed mapping algorithm by
      testing the accuracy of predicting EQ-5D-3L index values from MSIS-29 among
      multiple sclerosis (MS) patients in Sweden. Methods: Cross-sectional individual
      level data were collected from population-based Swedish registers between 2011
      and 2014. Health-related quality of life was assessed through MSIS-29 and EQ-5D
      3L at one point in time among 767 individuals with known disability level of MS.
      A previously developed mapping algorithm was applied to predict EQ-5D index
      values from MSIS-29 items, and the predictive accuracy was assessed through mean
      absolute error and root mean square error. Results: When applying the algorithm,
      the predicted mean EQ-5D-3L index value was 0.77 compared to the observed mean
      index value of 0.75. Prediction error was higher for individuals reporting EQ-5D
      values <0.5 compared to individuals reporting EQ-5D values >=0.5. Mean absolute
      error (0.12) and root mean square error (0.18) were smaller or equal to the
      prediction errors found in the original mapping study. Conclusion: The mapping
      algorithm had similar predictive accuracy in the two independent samples although
      results showed that the highest predictive performance was found in groups with
      better health. Varied predictive accuracy in subgroups is consistent with
      previous studies and strategies to deal with this are warranted.

PMID- 30288417
TI  - Costs and Benefits of Including Inactivated in Addition to Oral Poliovirus
      Vaccine in Outbreak Response After Cessation of Oral Poliovirus Vaccine Use.
AB  - Background: After stopping serotype 2-containing oral poliovirus vaccine use,
      serotype 2 poliovirus outbreaks may still occur and require outbreak response
      supplemental immunization activities (oSIAs). Current oSIA plans include the use
      of both serotype 2 monovalent oral poliovirus vaccine (mOPV2) and inactivated
      poliovirus vaccine (IPV). Methods: We used an existing model to compare the
      effectiveness of mOPV2 oSIAs with or without IPV in response to a hypothetical
      postcessation serotype 2 outbreak in northwest Nigeria. We considered strategies
      that co-administer IPV with mOPV2, use IPV only for older age groups, or use only
      IPV during at least one oSIA. We considered the cost and supply implications and
      estimated from a societal perspective the incremental cost-effectiveness and
      incremental net benefits of adding IPV to oSIAs in the context of this
      hypothetical outbreak in 2017. Results: Adding IPV to the first or second oSIA
      resulted in a 4% to 6% reduction in expected polio cases compared to exclusive
      mOPV2 oSIAs. We found the greatest benefit of IPV use if added preemptively as a
      ring around the initial oSIA target population, and negligible benefit if added
      to later oSIAs or older age groups. We saw an increase in expected polio cases if
      IPV replaced mOPV2 during an oSIA. None of the oSIA strategies that included IPV
      for this outbreak represented a cost-effective or net beneficial intervention
      compared to reliance on mOPV2 only. Conclusions: While adding IPV to oSIAs
      results in marginal improvements in performance, the poor cost-effectiveness and
      current limited IPV supply make it economically unattractive for high-risk
      settings in which IPV does not significantly affect transmission.

PMID- 30288418
TI  - Illustration of the Impact of Unmeasured Confounding Within an Economic
      Evaluation Based on Nonrandomized Data.
AB  - Background: Propensity score (PS) methods are frequently used within economic
      evaluations based on nonrandomized data to adjust for measured confounders, but
      many researchers omit the fact that they cannot adjust for unmeasured
      confounders. Objective: To illustrate how confounding due to unmeasured
      confounders can bias an economic evaluation despite PS matching. Methods: We used
      data from a previously published nonrandomized study to select a prematched
      population consisting of 121 patients (46.5%) who received endovascular aneurysm
      repair (EVAR) and 139 patients (53.5%) who received open surgical repair (OSR),
      in which sufficient data regarding eight measured confounders were available. One
      to-one PS matching was used within this population to select two PS-matched
      subpopulations. The Matched PS-Smoking Excluded Subpopulation was selected by
      matching patients using a PS model that omitted patients' smoking status (one of
      the measured confounders), whereas the Matched PS-Smoking Included Subpopulation
      was selected by matching patients using a PS model that included all eight
      measured confounders. Incremental cost-effectiveness ratios (ICERs) were assessed
      within both subpopulations. Results: Both subpopulations were composed of two
      different sets of 164 patients. Balance within the Matched PS-Smoking Excluded
      Subpopulation was achieved on all confounders except for patients' smoking
      status, whereas balance within the Matched PS-Smoking Included Subpopulation was
      achieved on all confounders. Results indicated that the ICER of EVAR over OSR
      differed between both subpopulations; the ICER was estimated at $157,909 per life
      year gained (LYG) within the Matched PS-Smoking Excluded Subpopulation, while it
      was estimated at $235,074 per LYG within the Matched PS-Smoking Included
      Subpopulation. Discussion: Although effective in controlling for measured
      confounding, PS matching may not adjust for unmeasured confounders that may bias
      the results of an economic evaluation based on nonrandomized data.

PMID- 30288420
TI  - Parental Preferences for the Organization of Preschool Vaccination Programs
      Including Financial Incentives: A Discrete Choice Experiment.
AB  - Objective: To establish preferences of parents and guardians of preschool
      children for the organization of preschool vaccination services, including
      financial incentives. Design: An online discrete choice experiment. Participants:
      Parents and guardians of preschool children (up to age 5 years) who were (n =
      259) and were not (n = 262) classified as at high risk of incompletely
      vaccinating their children. High risk of incomplete vaccination was defined as
      any of the following: aged less than 20 years, single parents, living in one of
      the 20% most deprived areas in England, had a preschool child with a disability,
      or had more than three children. Main Outcome Measures: Participant preferences
      expressed as positive (utility) or negative (disutility) on eight attributes and
      levels describing the organization of preschool vaccination programs. Results:
      There was no difference in preference for parental financial incentives compared
      to no incentive in parents "not at high risk" of incomplete vaccination. Parents
      who were "at high risk" expressed utility for cash incentives. Parents "at high
      risk" of incomplete vaccination expressed utility for information on the risks
      and benefits of vaccinations to be provided as numbers rather than charts or
      pictures. Both groups preferred universally available, rather than targeted,
      incentives. Utility was identified for shorter waiting times, and there were
      variable preferences for who delivered vaccinations. Conclusions: Cash incentives
      for preschool vaccinations in England would be welcomed by parents who are "at
      high risk" of incompletely vaccinating their children. Further work is required
      on the optimal mode and form of presenting probabilistic information on
      vaccination to parents/guardians, including preferences on mandatory vaccination
      schemes.

PMID- 30288419
TI  - Encouraging Medicare Advantage Enrollees to Switch to Higher Quality Plans:
      Assessing the Effectiveness of a "Nudge" Letter.
AB  - There are considerable quality differences across private Medicare Advantage
      insurance plans, so it is important that beneficiaries make informed choices.
      During open enrollment for the 2013 coverage year, the Centers for Medicare &
      Medicaid Services sent letters to beneficiaries enrolled in low-quality Medicare
      Advantage plans (i.e., plans rated less than 3 stars for at least 3 consecutive
      years by Medicare) explaining the stars and encouraging them to reexamine their
      choices. To understand the effectiveness of these low-cost, behavioral "nudge"
      letters, we used a beneficiary-level national retrospective cohort and performed
      multivariate regression analysis of plan selection during the 2013 open
      enrollment period among those enrolled in plans rated less than 3 stars. Our
      analysis controls for beneficiary demographic characteristics, health and health
      care spending risks, the availability of alternative higher rated plan options in
      their local market, and historical disenrollment rates from the plans. We
      compared the behaviors of those beneficiaries who received the nudge letters with
      those who enrolled in similar poorly rated plans but did not receive such
      letters. We found that beneficiaries who received the nudge letter were almost
      twice as likely (28.0% [95% confidence interval = 27.7%, 28.2%] vs. 15.3% [95%
      confidence interval = 15.1%, 15.5%]) to switch to a higher rated plan compared
      with those who did not receive the letter. White beneficiaries, healthier
      beneficiaries, and those residing in areas with more high-performing plan choices
      were more likely to switch plans in response to the nudge. Our findings highlight
      both the importance and efficacy of providing timely and actionable information
      to beneficiaries about quality in the insurance marketplace to facilitate
      informed and value-based coverage decisions.

PMID- 30288421
TI  - Efficient and Fair Heart Allocation Policies for Transplantation.
AB  - Background: The optimal allocation of limited donated hearts to patients on the
      waiting list is one of the top priorities in heart transplantation management. We
      developed a simulation model of the US waiting list for heart transplantation to
      investigate the potential impacts of allocation policies on several outcomes such
      as pre- and posttransplant mortality. Methods: We used data from the United
      Network for Organ Sharing (UNOS) and the Scientific Registry of Transplant
      Recipient (SRTR) to simulate the heart allocation system. The model is validated
      by comparing the outcomes of the simulation with historical data. We also adapted
      fairness schemes studied in welfare economics to provide a framework to assess
      the fairness of allocation policies for transplantation. We considered three
      allocation policies, each a modification to the current UNOS allocation policy,
      and analyzed their performance via simulation. The first policy broadens the
      geographical allocation zones, the second modifies the health status order for
      receiving hearts, and the third prioritizes patients according to their waiting
      time. Results: Our results showed that the allocation policy similar to the
      current UNOS practice except that it aggregates the three immediate geographical
      allocation zones, improves the health outcomes, and is "closer" to an optimal
      fair policy compared to all other policies considered in this study.
      Specifically, this policy could have saved 319 total deaths (out of 3738 deaths)
      during the 2006 to 2014 time horizon, in average. This policy slightly differs
      from the current UNOS allocation policy and allows for easy implementation.
      Conclusion: We developed a model to compare the outcomes of heart allocation
      policies. Combining the three immediate geographical zones in the current
      allocation algorithm could potentially reduce mortality rate and is closer to an
      optimal fair policy.

PMID- 30288423
TI  - Life Expectancy Predictions for Older Diabetic Patients as Estimated by
      Physicians and a Prognostic Model.
AB  - : Background: Multiple medical organizations recommend using life expectancy (LE)
      to individualize diabetes care goals. We compare the performance of patient LE
      predictions made by physicians to LE predictions from a simulation model (the
      Chicago model) in a cohort of older diabetic patients. DESIGN: Retrospective
      cohort study of a convenience sample (n = 447) of diabetes patients over 65 years
      and their physicians. Measurements: Physicians provided LE estimates for
      individual patients during a baseline survey (2000-2003). The prognostic model
      included a comprehensive geriatric type 2 diabetes simulation model (the Chicago
      model) and combinations of the physician estimate and the Chicago model ("And,"
      "Or," and "Average" models). Observed survival was determined based on the
      National Death Index through 31 December 2010. The predictive accuracy of LE
      predictions was assessed using c-statistic for 5-year mortality; Harrell's c
      statistic, and Integrated Brier score for overall survival. Results: The patient
      cohort had a mean (SD) age of 73.4 (5.9) years. The majority were female (62.6%)
      and black (79.4%). At 5 years, 108 (24.2%) patients had died. The c-statistic for
      5-year mortality was similar for physicians (0.69) and the Chicago model (0.68),
      while the average of estimates by physicians and Chicago model yielded the
      highest c-statistic of any method tested (0.73). The estimates of overall
      survival yielded a similar pattern of results. Limitations: Generalizability of
      patient cohort and lack of updated model parameters. Conclusions: Compared with
      individual methods, the average of LE estimates by physicians and the Chicago
      model had the best predictive performance. Prognostic models, such as the Chicago
      model, may complement and support physicians' intuitions as they consider
      treatment decisions and goals for older patients with chronic conditions like
      diabetes.

PMID- 30288424
TI  - Tailoring Educational and Behavioral Interventions to Level of Health Literacy: A
      Systematic Review.
AB  - Background: The relative value of universal compared to contingent approaches to
      communication and behavioral interventions for persons of low health literacy
      remains unknown. Objective: To examine the effectiveness of interventions that
      are tailored to individual health literacy level compared to nontailored
      interventions on health-related outcomes. Design: Systematic review. Data
      Sources: PubMed and Embase databases. Eligibility Criteria: Studies were eligible
      if they were in English, used an experimental or observational design, included
      an intervention that was tailored based on the individual's level of education,
      health literacy or health numeracy, and had a comparator group in which the
      intervention was not tailored to individual characteristics. Review Methods:
      Databases were searched from inception to January 2016, and the retrieved
      reference lists hand searched. Abstracts that met PICOS criteria underwent dual
      review for data extraction to assess study details and study quality. A
      qualitative synthesis was conducted. Results: Of 2,323 unique citations, 458
      underwent full review, and 9 met criteria for the systematic review. Five studies
      were positive and rated as good quality, 3 were negative with 2 of those of good
      quality, and 1 had mixed results (fair quality). Positive studies were conducted
      in the clinical domains of hypertension, diabetes, and depression with
      interventions including educational materials, disease management sessions,
      literacy training, and physician notification of limited health literacy among
      patients. Negative studies were conducted in the clinical domains of heart
      disease, glaucoma, and nutrition with interventions including medication
      reconciliation and educational materials. Conclusions: Tailoring communication
      and behavioral interventions to the individual level of health literacy may be an
      effective strategy to improve knowledge and indicators of disease control in
      selected clinical settings.

PMID- 30288422
TI  - Adjuvant Versus Salvage Radiotherapy for Patients With Adverse Pathological
      Findings Following Radical Prostatectomy: A Decision Analysis.
AB  - Background: Patients undergoing surgery for prostate cancer who have adverse
      pathological findings experience high rates of recurrence. While there are data
      supporting adjuvant radiotherapy compared to a wait-and-watch strategy to reduce
      recurrence rates, there are no randomized controlled trials comparing adjuvant
      radiotherapy with the other standard of care, salvage radiotherapy (radiotherapy
      administered at the time of recurrence). Methods: We constructed a health state
      transition (Markov) model employing two-dimensional Monte Carlo simulation using
      a lifetime horizon to compare the quality-adjusted survival associated with
      postoperative strategies using adjuvant or salvage radiotherapy. Prior to
      analysis, we calibrated and validated our model using the results of previous
      randomized controlled trials. We considered clinically important oncological
      health states from immediately postoperative to prostate cancer-specific death,
      commonly described complications from prostate cancer treatment, and other causes
      of mortality. Transition probabilities and utilities for disease states were
      derived from a literature search of MEDLINE and expert consensus. Results:
      Salvage radiotherapy was associated with an increased quality-adjusted life
      expectancy (QALE) (58.3 months) as compared with adjuvant radiotherapy (53.7
      months), a difference of 4.6 months (standard deviation 8.8). Salvage
      radiotherapy had higher QALE in 53% of hypothetical cohorts. There was a minimal
      difference in overall life expectancy (-0.1 months). Examining recurrence rates,
      our model showed validity when compared with available randomized controlled
      data. Conclusions: A salvage radiotherapy strategy appears to provide improved
      QALE for patients with adverse pathological findings following radical
      prostatectomy, compared with adjuvant radiotherapy. As these findings reflect,
      population averages, specific patient and tumor factors, and patient preferences
      remain central for individualized management.

PMID- 30288425
TI  - Development, Validation, and Implementation of a Medical Judgment Metric.
AB  - Background: Medical decision making is a critical, yet understudied, aspect of
      medical education. Aims: To develop the Medical Judgment Metric (MJM), a
      numerical rubric to quantify good decisions in practice in simulated
      environments; and to obtain initial preliminary evidence of reliability and
      validity of the tool. Methods: The individual MJM items, domains, and sections of
      the MJM were built based on existing standardized frameworks. Content validity
      was determined by a convenient sample of eight experts. The MJM instrument was
      pilot tested in four medical simulations with a team of three medical raters
      assessing 40 participants with four levels of medical experience and skill.
      Results: Raters were highly consistent in their MJM scores in each scenario
      (intraclass correlation coefficient 0.965 to 0.987) as well as their evaluation
      of the expected patient outcome (Fleiss's Kappa 0.791 to 0.906). For each
      simulation scenario, average rater cut-scores significantly predicted expected
      loss of life or stabilization (Cohen's Kappa 0.851 to 0.880). Discussion: The MJM
      demonstrated preliminary evidence of reliability and validity.

PMID- 30288426
TI  - Shared Decision-Making Tool for Self-Management of Home Therapies for Patients
      With Cystic Fibrosis.
AB  - Objective: Patients with cystic fibrosis (CF) undertake time-consuming programs
      of home therapies. Our objective was to develop a tool to help CF patients
      prioritize personal goals for some of these treatments. We describe the
      development and results of initial evaluation of this shared decision-making
      tool. Methods: Multicriteria decision-making method to develop a shared decision
      making tool that integrates patient's values and perceptions of treatment impact
      on functionality/sense of well-being. Treatment efficacy data obtained through
      comprehensive review of English language literature and Cochrane reviews. Field
      study of 21 patients was performed to assess acceptability of the approach,
      understandability of the tool, and to determine whether there was sufficient
      patient-to-patient variability in treatment goals and patient preferences to make
      use of a personalized tool worthwhile. Results: Patients found the tool easy to
      understand and felt engaged as active participants in their care. The tool was
      responsive to variations in patient preferences. Priority scores were calculated
      (0-1.0 +/- SD). Patients' most important treatment goals for improving lung
      health included improving breathing function (0.27 +/- 0.11), improving
      functionality/sense of well-being (0.24 +/- 0.13), preventing lung infection
      (0.21 +/- 0.08), minimizing time to complete treatments (0.16 +/- 0.12), and
      minimizing cost (0.11 +/- 0.09). Conclusions: A shared decision-making tool that
      integrates patients' values and best evidence is feasible and could result in
      improved patient engagement in their own care.

PMID- 30288428
TI  - Perspectives, Decision Making, and Final Mode of Delivery in Pregnant Women With
      a Previous C-Section in a General Hospital in Peru: Prospective Analysis.
AB  - : Objective: Explore the perspectives, decision-making process, and final mode of
      delivery among pregnant women with a previous C-section (Cesarean section) in a
      general public sector hospital in Lima, Peru. Methods: A qualitative prospective
      study using semistructured interviews at two time points in the outpatient
      obstetrics and gynecology clinic of a public sector, university-affiliated
      reference hospital in Lima, Peru. Seventeen adult pregnant women with a prior C
      section who were deemed by their attending obstetrician to be candidates for a
      trial of labor were interviewed. The first interview was between 37 and 38 weeks
      of pregnancy, and the second interview was 24 to 48 hours after delivery. MAIN
      OUTCOME MEASURES: Predelivery decision-making process and final mode of delivery.
      Results: Among the 17 participants, about half (9) of the participants stated
      that the physician explained that they had two approaches for delivery, a trial
      of labor after C-section (TOLAC) or elective repeated C-section (ERCD). Two women
      stated that their respective providers explained only one option, either an ERCD
      or TOLAC. However, 6 women did not receive any information from their providers
      about their delivery options. Of the 10 participants that decided TOLAC, 8 ended
      up having a C-section, and of the 7 patients that had planned an ERCD, 1 ended up
      having a vaginal delivery. Conclusion: Many participants affirmed that they made
      the decision about their approach of delivery. However, most of the participants
      that decided a TOLAC ended up having a C-section because of complications during
      the final weeks of pregnancy or during labor.

PMID- 30288427
TI  - Mapping MOS-HIV to HUI3 and EQ-5D-3L in Patients With HIV.
AB  - Objectives: The Medical Outcomes Study HIV Health Survey (MOS-HIV) is frequently
      used in HIV clinical trials; however, scores generated from the MOS-HIV are not
      suited for cost-effectiveness analyses as they do not assign utility values to
      health states. Our objective was to estimate and externally validate several
      mapping algorithms to predict Health Utilities Index Mark 3 (HUI3) and EQ-5D-3L
      utility values from the MOS-HIV. Methods: We developed and validated mapping
      algorithms using data from two HIV clinical trials. Data from the first trial (n
      = 367) formed the estimation data set for the HUI3 (4,610 observations) and EQ-5D
      3L (4,662 observations) mapping algorithms; data from the second trial (n = 168)
      formed the HUI3 (1,135 observations) and EQ-5D-3L (1,152 observations) external
      validation data set. We compared ordinary least squares (OLS) models of
      increasing complexity with the more flexible two-part, beta regression, and
      finite mixture models. We assessed model performance using mean absolute error
      (MAE) and mean squared error (MSE). Results: The OLS model that used MOS-HIV
      dimension scores along with squared terms gave the best HUI3 predictions (mean
      observed 0.84; mean predicted 0.80; MAE 0.0961); the finite mixture model gave
      the best EQ-5D-3L predictions (mean observed 0.90; mean predicted 0.88; MAE
      0.0567). All models produced higher prediction errors at the lower end of the
      HUI3 and EQ-5D-3L score ranges (<0.40). Conclusions: The proposed mapping
      algorithms can be used to predict HUI3 and EQ-5D-3L utility values from the MOS
      HIV, although greater error may pose a problem in samples where a substantial
      proportion of patients are in poor health. These algorithms may be useful for
      estimating utility values from the MOS-HIV for cost-effectiveness studies when
      HUI3 or EQ-5D-3L data are not available.

PMID- 30288429
TI  - Black-White Cardiovascular Disease Disparities After Target-Based Versus
      Personalized Benefit-Based Lipid and Blood Pressure Treatment.
AB  - Background: Cardiovascular disease (CVD) remains the leading cause of black-white
      morbidity and mortality disparities in the United States. Objectives: We sought
      to compare black-white CVD morbidity and mortality if lipid and blood pressure
      treatments were prescribed to achieve targeted lipid and blood pressure levels
      (treat-to-target [TTT]) or personalized CVD risk and treatment benefit estimates
      (benefit-based tailored treatment [BTT]). Methods: We utilized a microsimulation
      model of statin and blood pressure treatment based on a TTT approach (Joint
      National Commission 7; Adult Treatment Panel III) or a BTT approach (treating
      those with 10-year CVD risk >=10%, a modification and extension of recent
      American College of Cardiology/American Heart Association guidelines). We input
      data from the National Health and Nutrition Examination Survey, isolating adults
      40 to 75 years of age without prior CVD events. Results: We observed that TTT
      would prevent fewer CVD events (17.0 events prevented per 1,000 whites, 22.2 per
      1,000 blacks) than the BTT approach (25.9 events prevented per 1,000 whites, 45.4
      per 1,000 blacks). TTT could lower the national black-white CVD event rate
      disparity from 23.1 excess events per 1,000 blacks to 17.9 excess events (-23%),
      while BTT could lower the disparity to 3.6 excess events (-84% overall). The
      inferiority of TTT to BTT remained consistent in sensitivity analyses testing
      alternative treatment targets and either over- or underestimation of risk by
      commonly used equations. Conclusions: A BTT approach to lipid and blood pressure
      treatment would be expected to prevent more CVD events in the overall population
      and more effectively reduce national black-white CVD disparities than a
      traditional TTT approach.

PMID- 30288430
TI  - Economic Evaluation Alongside a Randomized Controlled Crossover Trial of Modified
      Group Cognitive-Behavioral Therapy for Anxiety Compared to Treatment-as-Usual in
      Adults With Asperger Syndrome.
AB  - Background: There is a growing interest in using group cognitive-behavioral
      therapy (CBT) with people who have Asperger syndrome (AS) and comorbid mental
      health problems. This study aims to assess the cost-effectiveness of modified
      group CBT for adults with AS experiencing co-occurring anxiety compared to
      treatment-as-usual. Methods: Economic evaluation alongside a pilot, multicenter,
      single-blind, randomized controlled crossover trial. Costs from the UK public
      sector (National Health Service and Social Services) and societal perspectives,
      quality-adjusted life years (QALYs), incremental net (monetary) benefit (INB),
      expected value of perfect information, expected value of sample information,
      expected net gain of sampling, and efficient sample size of a future trial are
      reported. Results: Over 48 weeks, from the societal perspective, CBT results in
      additional costs of L6,647, with only a 0.015 incremental gain in QALYs, leading
      to a negative INB estimate of L6,206 and a 23% probability of cost-effectiveness
      at a threshold of L30,000/QALY. Results from sensitivity analyses support the
      unlikely cost-effectiveness of CBT but indicate the potential for cost
      effectiveness over longer time horizons. Eliminating decision uncertainty is
      valued at L277 million, and the efficient sample size for a future trial is
      estimated at 1,200 participants per arm. Limitations: Relatively small sample
      size and prevalence of missing data present challenges to the interpretation of
      the results. Conclusions: Current evidence from this small pilot study suggests
      that, on average, modified group CBT is not cost-effective. However, there is
      much decision uncertainty so such a conclusion could be wrong. A large, full
      scale trial to reduce uncertainty would be an efficient investment for the UK
      health economy.

PMID- 30288431
TI  - Comparative Effectiveness of Up To Three Lines of Chemotherapy Treatment Plans
      for Metastatic Colorectal Cancer.
AB  - Modern chemotherapy agents transformed standard care for metastatic colorectal
      cancer (mCRC) but raised concerns about the financial burden of the disease. We
      studied comparative effectiveness of treatment plans that involve up to three
      lines of therapies and impact of treatment sequencing on health and cost
      outcomes. We employed a Markov model to represent the dynamically changing health
      status of mCRC patients and used Monte-Carlo simulation to evaluate various
      treatment plans consistent with existing guidelines. We calibrated our model by a
      meta-analysis of published data from an extensive list of clinical trials and
      measured the effectiveness of each plan in terms of cost per quality-adjusted
      life year. We examined the sensitivity of our model and results with respect to
      key parameters in two scenarios serving as base case and worst case for patients'
      overall and progression-free survivals. The derived efficient frontiers included
      seven and five treatment plans in base case and worst case, respectively. The
      incremental cost-effectiveness ratio (ICER) ranged between $26,260 and $152,530
      when the treatment plans on the efficient frontiers were compared against the
      least costly efficient plan in the base case, and between $21,256 and $60,040 in
      the worst case. All efficient plans were expected to lead to fewer than 2.5
      adverse effects and on average successive adverse effects were spaced more than 9
      weeks apart from each other in the base case. Based on ICER, all efficient
      treatment plans exhibit at least 87% chance of being efficient. Sensitivity
      analyses show that the ICERs were most dependent on drug acquisition cost,
      distributions of progression-free and overall survivals, and health utilities. We
      conclude that improvements in health outcomes may come at high incremental costs
      and are highly dependent in the order treatments are administered.

PMID- 30288432
TI  - Evidenced-Based Claims About Evidence.

PMID- 30288433
TI  - Implications of True and Perceived Treatment Burden on Cardiovascular Medication
      Use.
AB  - : Background: Clinical decisions require weighing possible risks and benefits,
      which are often based on the provider's sense of treatment burden. Patients often
      have a different view of how heavily treatment burden should be weighted.
      Objective: To examine how much small variations in patient treatment burden would
      influence optimal use of antihypertensive medications and how much over- and
      undertreatment can result from clinicians misunderstanding their patients'
      values. Methods: Analysis-Markov chain model. Data sources-Existing literature,
      including an individual-level meta-analysis of blood pressure trials. Target
      population-US representative sample, ages 40 to 85, no history of cardiovascular
      disease. Time horizon-Effect of 10 years of treatment on estimated lifetime
      quality-adjusted life-year (QALY) burden. Perspective-Patient. OUTCOME MEASURES:
      QALYs gained by treatment. Results: Fairly small differences in true patient
      burden from blood pressure treatment alter the number of blood pressure
      medications that should be recommended and alters treatment's potential benefit
      dramatically. We also found that a clinician misunderstanding the patient's
      burden could lead to almost 30% of patients being treated inappropriately.
      Limitations: Our results are based on simulation modeling. Conclusions: Clinical
      decisions that fail to account for patient treatment burden can mistreat a very
      large proportion of the public. Successful treatment choices closely depend on a
      clinician's ability to accurately gauge a patient's treatment burden.

PMID- 30288434
TI  - Understanding Midwives' Preferences for Providing Information About Newborn
      Bloodspot Screening.
AB  - Background: Understanding preferences for information provision in the context of
      health care service provision is challenging because of the number of potential
      attributes that may influence preferences. This study aimed to identify midwives'
      preferences for the process and outcomes of information provision in an expanded
      national newborn bloodspot screening program. Design: A sample of practicing
      midwives completed a hybrid-stated preference survey including a conjoint
      analysis (CA) and discrete choice experiment to quantify preferences for the
      types of, and way in which, information should be provided in a newborn bloodspot
      screening program. Six conjoint analysis questions captured the impact of
      different types of information on parents' ability to make a decision, and 10
      discrete choice experiment questions identified preferences for four process
      attributes (including parents' ability to make a decision). Results: Midwives
      employed by the UK National Health Service (n = 134) completed the survey. All
      types of information content were perceived to improve parents' ability to make a
      decision except for the possibility of false-positive results. Late pregnancy was
      seen to be the best time to provide information, followed by day 3 postbirth.
      Information before 20 weeks of pregnancy was viewed as reducing parents' ability
      to make a decision. Midwives preferred information to be provided by an
      individual discussion and did not think parents should receive information on the
      Internet. Conclusion: A hybrid stated preference survey design identified that a
      wide variety of information should be provided to maximize parents' ability to
      make a decision ideally provided late in pregnancy or on day 3 postbirth.

PMID- 30288436
TI  - Active Choice Intervention Increases Advance Directive Completion: A Randomized
      Trial.
AB  - Background. Many people recognize the potential benefits of advance directives
      (ADs), yet few actually complete them. It is unknown whether an active choice
      intervention influences AD completion. Methods. New employees were randomized to
      an active choice intervention (n = 642) or usual care (n = 637). The active
      choice intervention asked employees to complete an AD, confirm prior AD
      completion, or fill out a declination form. In usual care, participants could
      complete an AD, confirm prior completion, or skip the task. We used multivariable
      logistic regression to assess the relationship between the intervention arm and
      both AD completion online and the return of a signed AD by mail, as well as
      assess interactions between intervention group and age, gender, race, and
      clinical degree status. Results. Participants assigned to the active choice
      intervention more commonly completed ADs online (35.1% v. 20.4%, P < 0.001) (odds
      ratio [OR] = 2.10; 95% confidence interval [CI] = 1.63-2.71; number needed to
      treat = 6.8) and returned signed ADs by mail (7.8% v. 3.9%, P = 0.003; number
      needed to treat = 25.6). The effect of the intervention was significantly greater
      among men (OR = 4.13; 95% CI = 2.32-7.35) than among women (OR = 1.74; 95% CI =
      1.30-2.32) (interaction P value < 0.001). Responses to all eight choices made in
      the ADs were similar between groups (all P > 0.10). Limitations. A young and
      healthy participant may not benefit from AD completion as an older or seriously
      ill patient would. Conclusions. The active choice intervention significantly
      increased the proportion of participants completing an AD without changing the
      choices in ADs. This relationship was especially strong among men and may be a
      useful method to increase AD completion rates without altering choices.

PMID- 30288435
TI  - Estimation of Input Costs for a Markov Model in a German Health Economic
      Evaluation of Newer Antidepressants.
AB  - Background: Estimating input costs for Markov models in health economic
      evaluations requires health state-specific costing. This is a challenge in mental
      illnesses such as depression, as interventions are not clearly related to health
      states. We present a hybrid approach to health state-specific cost estimation for
      a German health economic evaluation of antidepressants. Methods: Costs were
      determined from the perspective of the community of persons insured by statutory
      health insurance ("SHI insuree perspective") and included costs for outpatient
      care, inpatient care, drugs, and psychotherapy. In an additional step, costs for
      rehabilitation and productivity losses were calculated from the societal
      perspective. We collected resource use data in a stepwise hierarchical approach
      using SHI claims data, where available, followed by data from clinical guidelines
      and expert surveys. Bottom-up and top-down costing approaches were combined.
      Results: Depending on the drug strategy and health state, the average input costs
      varied per patient per 8-week Markov cycle. The highest costs occurred for
      agomelatine in the health state first-line treatment (FT) ("FT relapse") with
      ?506 from the SHI insuree perspective and ?724 from the societal perspective.
      From both perspectives, the lowest costs (excluding placebo) were ?55 for
      selective serotonin reuptake inhibitors in the health state "FT remission."
      Conclusion: To estimate costs in health economic evaluations of treatments for
      depression, it can be necessary to link different data sources and costing
      approaches systematically to meet the requirements of the decision-analytic
      model. As this can increase complexity, the corresponding calculations should be
      presented transparently. The approach presented could provide useful input for
      future models.

PMID- 30288437
TI  - Should We Use the IMPACT-Model for the Outcome Prognostication of TBI Patients? A
      Qualitative Study Assessing Physicians' Perceptions.
AB  - Introduction. Shared Decision-Making may facilitate information exchange,
      deliberation, and effective decision-making, but no decision aids currently exist
      for difficult decisions in neurocritical care patients. The International Patient
      Decision Aid Standards, a framework for the creation of high-quality decision
      aids (DA), recommends the presentation of numeric outcome and risk estimates.
      Efforts are underway to create a goals-of-care DA in critically-ill traumatic
      brain injury (ciTBI) patients. To inform its content, we examined physicians'
      perceptions, and use of the IMPACT-model, the most widely validated ciTBI outcome
      model, and explored physicians' preferences for communicating prognostic
      information towards families. Methods. We conducted a qualitative study using
      semi-structured interviews in 20 attending physicians (neurosurgery,neurocritical
      care,trauma,palliative care) at 7 U.S. academic medical centers. We used
      performed qualitative content analysis of transcribed interviews to identify
      major themes. Results. Only 12 physicians (60%) expressed awareness of the IMPACT
      model; two stated that they "barely" knew the model. Seven physicians indicated
      using the model at least some of the time in clinical practice, although none
      used it exclusively to derive a patient's prognosis. Four major themes emerged:
      the IMPACT-model is intended for research but should not be applied to individual
      patients; mistrust in the IMPACT-model derivation data; the IMPACT-model is
      helpful in reducing prognostic variability among physicians; concern that
      statistical models may mislead families about a patient's prognosis. Discussion:
      Our study identified significant variability of the awareness, perception, and
      use of the IMPACT-model among physicians. While many physicians prefer to avoid
      conveying numeric prognostic estimates with families using the IMPACT-model,
      several physicians thought that they "ground" them and reduce prognostic
      variability among physicians. These findings may factor into the creation and
      implementation of future ciTBI-related DAs.

PMID- 30288439
TI  - Comparing and Monitoring Risk-Adjusted Hospital Performance Measures: A Weighted
      Estimating Equations Approach.
AB  - Background. There is a great deal of interest in evaluating hospital performance
      in order to monitor and improve health care quality. Increasingly, risk-adjusted
      performance measures are available to the public and statistical approaches for
      estimating these measures are considered. Some methods in use currently are based
      on 3-year aggregates of data since a small number of cases may lead to imprecise
      estimates and make it hard for stakeholders to detect differences across
      hospitals over time. However, if quality changes over time, a measure based on
      these data is a biased estimate of present performance. Methods. We present an
      alternative approach (weighted estimating equations [WEE]) for combining
      historical data in estimation that regulates the tradeoff between bias and
      precision in the measure of present performance. The WEE approach uses all
      available historical data through estimating functions that down-weight past
      data. Results. We compare the WEE approach to two current practices using a
      realistic dataset of the mortality of patients following an elective percutaneous
      coronary intervention procedure in New York State who meet certain criteria. The
      width of the uncertainty interval in the realistic example is up to 65% smaller
      and the difference is more pronounced for hospitals with a small number of cases.
      Conclusions. The advantage of this approach extends from the example dataset to
      other datasets. The WEE approach uses all available data rather than data from an
      arbitrary 3-year window. The effect of borrowing strength from historical data is
      a more precise estimate of present performance than current practices. Its
      advantages are important for the comparison of other aspects of medical
      performance, including surgical or medical practitioner performance.

PMID- 30288438
TI  - Access Is Necessary but Not Sufficient: Factors Influencing Delay and Avoidance
      of Health Care Services.
AB  - Background: Despite recently expanded access to health insurance, consumers still
      face barriers to using their coverage to obtain needed health care. Objective: To
      examine the characteristics of those who delay or avoid health care due to costs.
      Methods: Participants were recruited via Amazon MTurk and completed a survey
      assessing demographic characteristics, financial toxicity, health care minimizer
      maximizer tendencies, health insurance knowledge, numeracy, delaying/avoiding any
      care, and delaying/avoiding six common health care services (three preventive and
      three nonpreventive services). Validated measures were used when available.
      Delay/avoidance behaviors were categorized into delaying/avoiding any care,
      preventive care, and nonpreventive care. Logistic regression models examined 1)
      financial toxicity, 2) minimizer-maximizer tendencies, 3) numeracy, 4) health
      insurance knowledge, and 5) knowledge of preventive care coverage separately on
      three forms of delay/avoidance behaviors, controlling for chronic conditions,
      insurance status, and/or income where appropriate. Results: Of 518 respondents,
      470 did not fail attention-check questions and were used in analyses. Forty-five
      percent of respondents reported delaying/avoiding care due to cost. Multivariable
      analyses found that financial toxicity was related to delaying/avoiding any care
      (odds ratio [OR] = 0.884, P < 0.001), preventive care (OR = 0.906, P < 0.001),
      and nonpreventive care (OR = 0.901, P < 0.001). A tendency to minimize seeking
      health care (OR = 0.734, P < 0.001) and lower subjective numeracy (OR = 0.794, P
      = 0.023) were related to delaying/avoiding any care. General health insurance
      knowledge (OR = 0.989, P = 0.023) and knowledge of preventive care coverage (OR =
      0.422, P < 0.001) were related to delaying/avoiding preventive care. Conclusions:
      Many people delay or avoid health care due to costs, even when insured. Results
      suggest that there may be different reasons individuals delay or avoid preventive
      and nonpreventive care. Findings may inform interventions to educate consumers
      and support discussions about health care costs to facilitate appropriate health
      care utilization.

PMID- 30288440
TI  - Cost Recommendations in the Second Edition of Cost-Effectiveness in Health and
      Medicine: A Review.
AB  - A 2nd edition of Cost-Effectiveness in Health and Medicine has now been published
      by a group of medical decision-making experts known collectively as the 2nd
      Panel. This is a critical review of the recommendations for how to deal with
      costs in cost-effectiveness analysis, recommendations that are contained in
      Chapter 8 of that edition, titled "Estimating Costs and Valuations of Non-Health
      Benefits in Cost-Effectiveness Analysis," authored primarily but not exclusively
      by Anirban Basu. This review focuses on the correspondence between the costs in
      the numerator of the incremental cost-effectiveness ratio (ICER) and what is
      measured in the denominator of the ICER by the quality-adjusted life years
      (QALYs). Although it raises a number of issues regarding what is actually being
      measured in the numerator and denominator of the ICER, it primarily challenges
      the 2nd Panel's recommendation that the costs of non-health consumption in any
      additional years of life generated by the intervention in question be accounted
      for in the numerator, even though no measures of the benefits are included in the
      QALYs in the denominator. This review is adapted from a review of the entire 2nd
      edition that was sent to the 2nd Panel steering committee on January 8, 2016.

PMID- 30288441
TI  - Individualized Colorectal Cancer Screening Discussions Between Older Adults and
      Their Primary Care Providers: A Cross-Sectional Study.
AB  - Introduction. Discussions of colorectal cancer (CRC) screening with older adults
      should be individualized to maximize appropriate screening. Our aim was to
      describe CRC screening discussions and explore their associations with patient
      characteristics and screening intentions. Methods. Cross-sectional survey of 422
      primary care patients aged >=70 years and eligible for CRC screening, including
      open-ended questions about CRC screening discussions. Primary outcomes were the
      frequency with which CRC screening discussions occurred, who had those
      discussions, and the domains that emerged from thematic analysis of participants'
      brief reports of their discussions. We also examined the associations between 1)
      patient characteristics and whether a screening discussion occurred and 2) the
      domains discussed and what screening decisions were made. Results. Of 422
      participants, 209 reported having discussions and 201 responded to open-ended
      questions about CRC discussions. In a regression analysis, several factors were
      associated with increased odds of having a discussion: participants' preference
      to pursue screening (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3, 3.9),
      good health (OR 2.9, 95% CI 1.7, 4.8), and receipt of the decision aid (OR 2.1,
      95% CI 1.4, 3.2). Our thematic analysis identified five domains related to
      discussion content and three related to discussion process. The CRC screening
      related information domain was the most commonly discussed content domain, and
      the timing/frequency domain was associated with increased odds of intent to
      pursue screening. Decision-making role, the most commonly discussed process
      domain, was associated with increased odds of the intent to forgo CRC screening.
      Conclusions and Relevance. CRC screening discussions varied by type of
      participant and content. Future work is needed to determine if interventions
      focused on specific domains alters the appropriateness of participants'
      colorectal cancer screening intentions.

PMID- 30288442
TI  - Organic Dissemination and Real-World Implementation of Patient Decision Aids for
      Left Ventricular Assist Device.
AB  - Background. Although patient decision aids (PtDAs) have been shown to improve
      patient knowledge and satisfaction, they are infrequently used in the real world.
      We aimed to understand how our publicly available PtDAs developed for destination
      therapy left ventricular assist device (DT LVAD) were implemented in clinical
      practice and characterize factors influencing adoption. Methods. We contacted 39
      people, 31 who had independently emailed inquiring about our DT LVAD PtDAs and 8
      identified through snowball sampling. Thirty people from 23 programs participated
      in semistructured interviews, which were analyzed using normalization process
      theory. Results. Eleven programs currently use the PtDAs, 5 plan to use them but
      have not yet, and 7 do not currently use them nor have active plans to use them.
      Due to major tradeoffs and preference sensitivity of the DT LVAD decision,
      participants recognized a role for shared decision making and a need for
      significant information transfer. Due to a relative lack of resources,
      participants saw the PtDAs as a way to help facilitate a higher quality decision
      making process. Limited time, lack of personnel, and perceived burden to
      implementing system-level change were cited as barriers to use. Initial
      implementation was accomplished by a champion of the PtDAs. Actual use of the
      PtDAs most commonly occurred through LVAD coordinators at the start of formal
      patient teaching sessions, where the PtDAs could be integrated into the existing
      LVAD consent and education structure. Conclusion. Interest in and implementation
      of PtDAs occurred independently at several LVAD programs due to a favorable
      decisional context, including a perceived role for shared decision making in the
      high-stakes decision around DT LVAD, unmet informational needs, preexisting
      education sessions, and invested clinical champions.

PMID- 30288444
TI  - Using a Patient Decision Aid Video to Assess Current and Former Smokers' Values
      About the Harms and Benefits of Lung Cancer Screening With Low-Dose Computed
      Tomography.
AB  - Background. Recent policy changes require discussing the potential benefits and
      harms of lung cancer screening with low-dose computed tomography. This study
      explored how current and former smokers value potential benefits and harms after
      watching a patient decision aid, and their screening intentions. Methods. Current
      or former smokers (quit within 15 years) with no history of lung cancer watched
      the decision aid and responded to items assessing the value of potential benefits
      and harms in their decision making, and their screening intentions. Results.
      After viewing the decision aid, participants (n = 30; mean age 61.5 years, mean
      30.4 pack-year history) were well-informed (mean 80.5% correct responses) and
      rated anticipated regret and finding cancer early as highly important in their
      decision (medians >9 out of 10), along with moderate but variable concerns about
      false positives, overdiagnosis, and radiation exposure (medians 7.0, 6.0, and
      5.0, respectively). Most participants (90.0% to 96.7%) felt clear about how they
      personally valued the potential benefits and harms and prepared for decision
      making (mean 86.7 out of 100, SD = 21.3). After viewing the decision aid, most
      participants (90%) intended to discuss screening with their doctor. Limitations.
      The study is limited to current and former smokers enrolled in a tobacco
      treatment program, and it may not generalize to other patient populations.
      Conclusions. The majority of current and former smokers were strongly concerned
      about anticipated regret and finding cancer early, while concerns about radiation
      exposure, false positives, and overdiagnosis were variable. After viewing the
      decision aid, current and former smokers reported strong preparedness and
      intentions to talk with their doctor about lung cancer screening with low-dose
      computed tomography.

PMID- 30288443
TI  - Electronically Verified Use of Internet-Based, Multimedia Decision Aids by
      Adolescents With Type 1 Diabetes and Their Caregivers.
AB  - Decision aids (DAs) are central to shared decision making (SDM) interventions,
      yet little is known about patients' actual DA use. Adequate utilization of DAs
      could optimize SDM effectiveness. Electronic DAs enable more objective tracking
      and analysis of actual DA utilization than do paper DAs. This report is part of
      an ongoing randomized controlled SDM trial enrolling adolescents with type 1
      diabetes and their caregivers (n = 153) who were considering use of an insulin
      pump or continuous glucose monitor. Extensive stakeholder engagement guided
      creation of two online DAs. After completing baseline measures, 133 dyads were
      randomized to SDM (access to the pertinent DA) or Usual Care (clinic routines for
      preparing candidates for adopting these devices). Utilization data showed that
      80% of caregivers and 66% of youths logged into a DA at least once; youths and
      caregivers, respectively, dedicated a mean of 44.7 and 55.0 minutes to website
      use and viewed 72.2% and 77.4% of the DA content. Median total duration from
      enrollment to last DA logout was 48.2 days for adolescents and 45.6 days for
      caregivers. Bivariate comparisons showed that non-Hispanic, Caucasian females
      from households with higher socioeconomic status were significantly more likely
      to login to the assigned DA at least once. Hierarchical multiple regression
      showed that adolescent males with lower levels of health literacy demonstrated
      fewer DA logins (F = 2.59; P < 0.009), but identified no significant predictors
      of adolescents' or caregiver' duration of DA use or proportion of DA content
      viewed. Future SDM trials should seek to promote DA use, especially by non-White
      adolescents, perhaps with direct assistance with the initial DA login. Trials
      employing electronic DAs should routinely report and analyze utilization data.

PMID- 30288445
TI  - Healthy, Wealthy, and Wise? Exploring Parent Comparative Optimism About Future
      Child Outcomes.
AB  - Objectives. Comparative optimism is present in parental predictions of their
      child's long-term, obesity-related health outcomes and some of this optimism is
      unrealistic. An understanding of how comparative optimism relates to parents'
      predictions of health versus other child outcomes could contribute to the
      development of interventions and strategies pediatricians can use to improve risk
      assessment. Methods. In a nationally representative survey, we asked American
      parents of 6- to 17-year-old children (n = 410) to estimate the chances that
      their child and "a typical child in their community" would be affected by
      overweight, get married, and complete a 4-year college degree by age 30, and the
      child's future salary at age 30. We collected data on family demographic and
      health characteristics. We modeled the difference in parent predictions for their
      child versus the typical child using multivariate linear regressions. Results.
      Compared to the typical child, parents were less likely to predict that their
      child would be affected by overweight (-26.6 percentage points, 95% confidence
      interval [CI]: -35.6, -17.7) and more likely to predict that their child would
      complete a 4-year degree (16.7 percentage points, 95% CI: 2.5, 31.0). Parents
      predicted their child would have a higher income than the typical child at age 30
      ($15,266, 95% CI: $7,487, $23,046). Parents did not predict that their child
      would be more likely than the typical child to be married by age 30 (-2.2
      percentage points, 95% CI: -8.1, 3.7). Conclusions. Some parents appear to
      exhibit comparative optimism around their child's future weight status,
      education, and economic outcomes, but not marriage. Future experimental work
      should assess whether risk communication approaches that consider optimism bias
      influence parent risk perception and parenting behaviors.

PMID- 30288446
TI  - Health Technology Optimization Analysis: Conceptual Approach and Illustrative
      Application.
AB  - We present a conceptual approach to determine the optimal solution to delivering
      a health technology, consistent with the objective of maximizing patient outcomes
      subject to resources available to a publicly funded health system. The article
      addresses two key policy questions: 1) adding system values through appropriate
      planning of health services delivery and 2) considering the tradeoff between
      patient outcomes and costs to the health system through appropriate use of health
      technologies for conditions with time-dependent treatment outcomes. We develop a
      health technology optimization framework that considers geographical variation
      and searches for the best delivery method through a pairwise comparison of all
      possible strategies, factoring in controlled variables including disease
      epidemiology, time or distance to hospitals, available medical services,
      treatment eligibility, treatment efficacy, and costs. Taking variations of these
      factors into account would help support a more efficient allocation of health
      resources. Drawing identified strategies together then creates a map of optimal
      strategies. We apply the proposed method to a policy-relevant health technology
      assessment of endovascular therapy (EVT) for treating acute ischemic stroke. The
      best strategy for providing EVT relies on the geographical location of stroke
      onset and the decision maker's preference for either patient outcomes or economic
      efficiency. The proposed method produced an optimization map showing the optimal
      strategy for EVT delivery, which maximizes patient outcomes while minimizing
      health system costs. In the illustrative case study, there were no tradeoffs
      between health outcomes and costs, meaning that the delivery strategies that were
      clinically optimal for patients were also the most cost-effective. In conclusion,
      the health technology optimization approach is a useful tool for informing
      implementation decisions and coordinating the delivery of complex health services
      such as EVT.

PMID- 30288447
TI  - Enhancing the Value of the ASCO Value Framework.

PMID- 30288449
TI  - An Informatics Approach to Implement Support for Shared Decision Making for
      Primary Prevention Statin Therapy.
AB  - Background. Shared decision making (SDM) is recommended prior to initiation of
      statin therapy for primary prevention but is underutilized. We designed an
      informatics decision-support tool to facilitate use of the Mayo Clinic Statin
      Choice decision aid at the point-of-care and evaluated its impact. Methods. Using
      an iterative approach, we designed and implemented a single-click decision
      support tool embedded within the electronic health records (EHRs) to automate the
      calculation of 10-year atherosclerotic cardiovascular disease (ASCVD) risk and
      populate the Statin Choice decision aid. We surveyed primary care providers at
      two clinics regarding their attitudes about SDM before and after deployment of
      intervention, as well as their usage of and perceived competence regarding SDM
      for primary prevention statin therapy. Three-month web traffic to the Statin
      Choice website was calculated before and after deployment of the intervention.
      Results. Pre-post surveys were completed by 60 primary care providers (24 [40%]
      attending physicians and 36 [60%] housestaff physicians). After deployment of the
      EHR tool, respondents were more aware of the Statin Choice decision aid (P <
      0.001), reported being more competent regarding SDM (P = 0.047), and reported
      using decision aids more often when considering statin initiation (P = 0.043).
      There was no significant change in attitudes about SDM as measured through the
      Patient Provider Orientation Scale (pre 4.23 +/- 0.40 v. post 4.16 +/- 0.38, P =
      0.11) and the SDM belief scale (pre 21.4 +/- 2.1 v. post 21.1 +/- 2.0, P = 0.35).
      Web-based usage rates for the Statin Choice decision aid increased from 3.4 to
      5.2 per 1,000 outpatient clinic visits (P = 0.002). Conclusions. Implementation
      of a point-of-care decision-support tool increased the usage of decision aids for
      primary prevention statin therapy. This effect does not appear to be mediated by
      any concomitant changes in physician attitude toward SDM.

PMID- 30288448
TI  - Population Health and Cost-Effectiveness Implications of a "Treat All"
      Recommendation for HCV: A Review of the Model-Based Evidence.
AB  - The World Health Organization HCV Guideline Development Group is considering a
      "treat all" recommendation for persons infected with hepatitis C virus (HCV). We
      reviewed the model-based evidence of cost-effectiveness and population health
      impacts comparing expanded treatment policies to more limited treatment access
      policies, focusing primarily on evaluations of all-oral directly acting
      antivirals published after 2012. Searching PubMed, we identified 2,917 unique
      titles. Sequentially reviewing titles and abstracts identified 226 potentially
      relevant articles for full-text review. Sixty-nine articles met all inclusion
      criteria-42 cost-effectiveness analyses and 30 models of population-health
      impacts, with 3 articles presenting both types of analysis. Cost-effectiveness
      studies for many countries concluded that expanding treatment to people with mild
      liver fibrosis, who inject drugs (PWID), or who are incarcerated is generally
      cost-effective compared to more restrictive treatment access policies at country
      specific prices. For certain patient subpopulations in some countries-for
      example, elderly individuals without fibrosis-treatment is only cost-effective at
      lower prices. A frequent limitation is the omission of benefits and consequences
      of HCV transmission (i.e., treatment as prevention; risks of reinfection), which
      may underestimate or overestimate the cost-effectiveness of a "treat all" policy.
      Epidemiologic modeling studies project that through a combination of prevention,
      aggressive screening and diagnosis, and prompt treatment for all fibrosis stages,
      it may be possible to virtually eliminate HCV in many countries. Studies show
      that if resources are not available to diagnose and treat all HCV-infected
      individuals, treatment prioritization may be needed, with alternative
      prioritization strategies resulting in tradeoffs between reducing mortality or
      reducing incidence. Notably, because most new HCV infections are among PWID in
      many settings, HCV elimination requires unrestricted treatment access combined
      with injection transmission disruption strategies. The model-based evidence
      suggests that a properly constructed strategy that substantially expands HCV
      treatment could achieve cost-effective improvements in population health in many
      countries.

PMID- 30288450
TI  - A Comparison Between Subjective and Objective Methods of Predicting Health Care
      Expenses to Support Consumers' Health Insurance Plan Choice.
AB  - Objective. Numerous electronic tools help consumers select health insurance plans
      based on their estimated health care utilization. However, the best way to
      personalize these tools is unknown. The purpose of this study was to compare two
      common methods of personalizing health insurance plan displays: 1) quantitative
      healthcare utilization predictions using nationally representative Medical
      Expenditure Panel Survey (MEPS) data and 2) subjective-health status predictions.
      We also explored their relations to self-reported health care utilization.
      Methods. Secondary data analysis was conducted with responses from 327 adults
      under age 65 considering health insurance enrollment in the Affordable Care Act
      (ACA) marketplace. Participants were asked to report their subjective health,
      health conditions, and demographic information. MEPS data were used to estimate
      predicted annual expenditures based on age, gender, and reported health
      conditions. Self-reported health care utilization was obtained for 120
      participants at a 1-year follow-up. Results. MEPS-based predictions and
      subjective-health status were related (P < 0.0001). However, MEPS-predicted
      ranges within subjective-health categories were large. Subjective health was a
      less reliable predictor of expenses among older adults (age * subjective health,
      P = 0.04). Neither significantly related to subsequent self-reported health care
      utilization (P = 0.18, P = 0.92, respectively). Conclusions. Because MEPS data
      are nationally representative, they may approximate utilization better than
      subjective health, particularly among older adults. However, approximating health
      care utilization is difficult, especially among newly insured. Findings have
      implications for health insurance decision support tools that personalize plan
      displays based on cost estimates.

PMID- 30288451
TI  - The Lifetime Health Burden of Delayed Graft Function in Kidney Transplant
      Recipients in the United States.
AB  - Background. Although delayed graft function (DGF) is associated with an increased
      risk of acute rejection and decreased graft survival, there are no estimates of
      the long-term or lifetime health burden of DGF. Objectives. To estimate the long
      term and lifetime health burden of DGF, defined as the need for at least one
      dialysis session within the first week after transplantation, for a cohort
      representative of patients who had their first kidney transplant in 2014.
      Methods. Data from the United States Renal Data System (USRDS; 2001-2014) were
      used to estimate a semi-Markov parametric multi-state model with three disease
      states. Maximum length of follow-up was 13.7 years, and a microsimulation model
      was used to extrapolate results over a lifetime. The impact of DGF was assessed
      by simulating the model for each patient in the cohort with and without DGF.
      Results. At the end of 13.7 years of follow-up, DGF reduces the probability of
      having a functioning graft from 52% to 32%, increases the probability of being on
      dialysis from 10% to 19%, and increases the probability of death from 38% to 50%
      relative to transplant recipients who do not experience DGF. A typical transplant
      recipient with DGF (median age = 53) is observed to lose 0.87 quality-adjusted
      life-years (QALYs). Extrapolated over a lifetime, the same 53-year-old DGF
      patient is projected to lose 3.01 (95% confidence interval: 2.33, 3.70) QALYs
      relative to a transplant recipient with the same characteristics who does not
      experience DGF. Conclusions. The lifetime health burden of DGF is substantial.
      Understanding these consequences will help health care providers weigh kidney
      transplant decisions and inform policies for patients in the context of varying
      risks of DGF.

PMID- 30288452
TI  - Occupational, physical, sexual and mental health and violence among migrant and
      trafficked commercial fishers and seafarers from the Greater Mekong Subregion
      (GMS): systematic review.
AB  - Background: Little is known about the health of GMS commercial fishers and
      seafarers, many of whom are migrants and some trafficked. This systematic review
      summarizes evidence on occupational, physical, sexual and mental health and
      violence among GMS commercial fishers/seafarers. Methods: We searched 5
      electronic databases and purposively searched grey literature. Quantitative or
      qualitative studies reporting prevalence or risk of relevant outcomes were
      included. Two reviewers independently screened articles. Data were extracted on
      nationality and long/short-haul fishing where available. Results: We identified
      33 eligible papers from 27 studies. Trafficked fishers/seafarers were included in
      n=12/13 grey literature and n=1/20 peer-reviewed papers. Among peer-reviewed
      papers: 11 focused on HIV/AIDS/sexual health; nine on occupational/physical
      health; one study included mental health of trafficked fishers. Violence was
      quantitatively measured in eight papers with prevalence of: 11-26% in port
      convenience samples; 68-100% in post-trafficking service samples. Commercial
      fishers/seafarers whether trafficked or not worked extremely long hours;
      trafficked long-haul fishers had very limited access to care following injuries
      or illness. Lesser-known risks reported among fishers included penile oil
      injections and beriberi. We found just one work safety intervention study and
      inconclusive evidence for differences in the outcomes by nationality. Findings
      are limited by methodological weaknesses of primary studies. Conclusion: Results
      show an absence of high-quality epidemiological studies beyond sexual health.
      Formative and pilot intervention research on occupational, physical and mental
      health among GMS commercial fishers and seafarers is needed. Future studies
      should include questions about violence and exploitation. Ethical and reporting
      standards of grey literature should be improved. Trial Registration: Review
      registration number: PROSPERO 2014: CRD42014009656.

PMID- 30288453
TI  - Sustainability of artisanal mining of cobalt in DR Congo.
AB  - The sustainability of cobalt is an important emerging issue because this critical
      base metal is an essential component of lithium-ion batteries for electric
      vehicles. More than half the world's cobalt mine production comes from the
      Katanga Copperbelt in DR Congo, with a substantial proportion (estimated at 15
      20%) being extracted by artisanal miners. Here we show, in a case study performed
      in the town of Kolwezi, that people living in a neighbourhood that had been
      transformed into an artisanal cobalt mine, had much higher levels of cobalt in
      urine and blood than people living in a nearby control area. The differences were
      most pronounced for children, in whom we also found evidence of exposure-related
      oxidative DNA damage. It was already known that industrial mining and processing
      of metals have led to severe environmental pollution in the region. This field
      study provides novel and robust empirical evidence that the artisanal extraction
      of cobalt that prevails in the DR Congo may cause toxic harm to vulnerable
      communities. This strengthens the conclusion that the currently existing cobalt
      supply chain is not sustainable.

PMID- 30288454
TI  - Purinergic Vasotoxicity: Role of the Pore/Oxidant/KATP Channel/Ca2+ Pathway in
      P2X7-Induced Cell Death in Retinal Capillaries.
AB  - P2X7 receptor/channels in the retinal microvasculature not only regulate
      vasomotor activity, but can also trigger cells in the capillaries to die. While
      it is known that this purinergic vasotoxicity is dependent on the transmembrane
      pores that form during P2X7 activation, events linking pore formation with cell
      death remain uncertain. To better understand this pathophysiological process, we
      used YO-PRO-1 uptake, dichlorofluorescein fluorescence, perforated-patch
      recordings, fura-2 imaging and trypan blue dye exclusion to assess the effects of
      the P2X7 agonist, benzoylbenzoyl-ATP (BzATP), on pore formation, oxidant
      production, ion channel activation, [Ca2+]i and cell viability. Experiments
      demonstrated that exposure of retinal microvessels to BzATP increases capillary
      cell oxidants via a mechanism dependent on pore formation and the enzyme, NADPH
      oxidase. Indicative that oxidation plays a key role in purinergic vasotoxicity,
      an inhibitor of this enzyme completely prevented BzATP-induced death. We further
      discovered that vasotoxicity was boosted 4-fold by a pathway involving the
      oxidation-driven activation of hyperpolarizing KATP channels and the resulting
      increase in calcium influx. Our findings revealed that the previously
      unappreciated pore/oxidant/KATP channel/Ca2+ pathway accounts for 75% of the
      capillary cell death triggered by sustained activation of P2X7 receptor/channels.
      Elucidation of this pathway is of potential therapeutic importance since
      purinergic vasotoxicity may play a role in sight-threatening disorders such as
      diabetic retinopathy.

PMID- 30288455
TI  - Implementation and Outcomes of a Community-Based Educational Program for
      Colorectal Cancer Prevention in Hispanics.
AB  - Objectives: Colorectal cancer (CRC) is the 2nd most diagnosed cancer and leading
      cause of cancer death in Puerto Rico. However, CRC screening rates remain low.
      The aim of this study was to test the effectiveness of a Train-the-Trainers'
      (TTT) program to develop trainers capable of educating others within their
      communities about CRC prevention. Methods: The TTT program consisted of didactics
      and seminars to capacitate participants to become trainers in CRC prevention.
      This project was evaluated using three components: (1) training workshops; (2)
      community educational sessions; and (3) the participant's experience as a
      trainer. Pre - and post-tests on CRC screening knowledge were given to TTT
      participants. Program effectiveness was determined by the pre- and post-tests,
      number of workshop participants completing a community educational session within
      three months of training and the number of community members reached. Results:
      Among the 115 total participants, 97 participants took the pre- and post-test.
      There was a significant difference in the scores for the pre-test (M = 10.56, SD
      = 2.57) and the post-test (M = 11.43, SD = 1.83) given; t (96) = -4.68, p <
      0.001. A total of 955 community members were reached. Participants from the
      community educational sessions (n = 680) evaluated the program. 77.7% of those
      participants expressed intent to undergo colonoscopy screening in the future.
      Conclusions: TTT was effective in preparing trainers in CRC prevention.
      Participants increased their knowledge about CRC prevention and successfully
      reached members of their community. Utilization of community trainers is an
      effective alternative to increase CRC education and awareness in Hispanic
      communities, which may positively impact CRC screening rates in this population.

PMID- 30288457
TI  - Solid-State Effects on the Optical Excitation of Push-Pull Molecular J-Aggregates
      by First-Principles Simulations.
AB  - J-aggregates are a class of low-dimensional molecular crystals which display
      enhanced interaction with light. These systems show interesting optical
      properties as an intense and narrow red-shifted absorption peak (J-band) with
      respect to the spectrum of the corresponding monomer. The need to theoretically
      investigate optical excitations in J-aggregates is twofold: a thorough first
      principles description is still missing and a renewed interest is rising recently
      in understanding the nature of the J-band, in particular regarding the collective
      mechanisms involved in its formation. In this work, we investigate the electronic
      and optical properties of a J-aggregate molecular crystal made of ordered
      arrangements of organic push-pull chromophores. By using a time-dependent density
      functional theory approach, we assess the role of the molecular packing in the
      enhancement and red shift of the J-band along with the effects of confinement in
      the optical absorption, when moving from bulk to low-dimensional crystal
      structures. We simulate the optical absorption of different configurations (i.e.,
      monomer, dimers, a polymer chain, and a monolayer sheet) extracted from the bulk
      crystal. By analyzing the induced charge density associated with the J-band, we
      conclude that it is a longitudinal excitation, delocalized along parallel linear
      chains and that its overall red shift results from competing coupling mechanisms,
      some giving red shift and others giving blue shift, which derive from both
      coupling between transition densities and renormalization of the single-particle
      energy levels.

PMID- 30288456
TI  - Novel 18F-Labeled PET Imaging Agent FV45 Targeting the Renin-Angiotensin System.
AB  - Renin-angiotensin system (RAS) plays an important role in the regulation of blood
      pressure and hormonal balance. Using positron emission tomography (PET)
      technology, it is possible to monitor the physiological and pathological
      distribution of angiotensin II type 1 receptors (AT1), which reflects the
      functionality of RAS. A new 18F-labeled PET tracer derived from the clinically
      used AT1 antagonist valsartan showing the least possible chemical alteration from
      the valsartan structure has been designed and synthesized with several
      strategies, which can be applied for the syntheses of further derivatives.
      Radioligand binding study showed that the cold reference FV45 (K i 14.6 nM) has
      almost equivalent binding affinity as its lead valsartan (K i 11.8 nM) and
      angiotensin II (K i 1.7 nM). Successful radiolabeling of FV45 in a one-pot
      radiofluorination followed by the deprotection procedure with 21.8 +/- 8.5%
      radiochemical yield and >99% radiochemical purity (n = 5) enabled a distribution
      study in rats and opened a path to straightforward large-scale production. A fast
      and clear kidney uptake could be observed, and this renal uptake could be
      selectively blocked by pretreatment with AT1-selective antagonist valsartan.
      Overall, as the first 18F-labeled PET tracer based on a derivation from
      clinically used drug valsartan with almost identical chemical structure,
      [18F]FV45 will be a new tool for assessing the RAS function by visualizing AT1
      receptor distributions and providing further information regarding cardiovascular
      system malfunction as well as possible applications in inflammation research and
      cancer diagnosis.

PMID- 30288458
TI  - Structure and Dynamics of tRNAMet Containing Core Substitutions.
AB  - The fidelity of protein synthesis is largely dominated by the accurate
      recognition of transfer RNAs (tRNAs) by their cognate aminoacyl-tRNA synthetases.
      Aminoacylation of each tRNA with its cognate amino acid is necessary to maintain
      the accuracy of genetic code input. Aminoacylated tRNAMet functions in both
      initiation and elongation steps during protein synthesis. As a precursor to the
      investigation of a methionyl-tRNA synthetase-tRNAMet complex, presented here are
      the results of molecular dynamics (MD) for single nucleotide substitutions in the
      D-loop of tRNAMet (G15A, G18A, and G19A) probing structure/function
      relationships. The core of tRNAMet likely mediates an effective communication
      between the tRNA anticodon and acceptor ends, contributing an acceptor stem
      rearrangement to fit into the enzyme-active site. Simulations of Escherichia coli
      tRNAMet were performed for 1 MUs four times each. The MD simulations showed
      changes in tRNA flexibility and long-range communication most prominently in the
      G18A variant. The results indicate that the overall tertiary structure of tRNAMet
      remains unchanged with these substitutions; yet, there are perturbations to the
      secondary structure. Network-based analysis of the hydrogen bond structure and
      correlated motion indicates that the secondary structure elements of the tRNA are
      highly intraconnected, but loosely interconnected. Specific nucleotides,
      including U8 and G22, stabilize the mutated structures and are candidates for
      substitution in future studies.

PMID- 30288459
TI  - Tetrabutylammonium Bromide-Promoted Metal-Free, Efficient, Rapid, and Scalable
      Synthesis of N-Aryl Amines.
AB  - A rapid, transition metal-free, high-yielding, tetrabutylammonium bromide
      promoted method of N-arylation is reported within. The optimized conditions
      tolerated a wide range of secondary amines and was equally effective with bromo-
      and chlorobenzene-including substituted aryl halides. The developed method is
      found to be effective for N-arylation when compared to earlier methods which
      involve harsh conditions, transition metals, lack of scalability, and long
      reaction times. Our method utilizes conventional heating only; it is readily
      scalable; and the products are facile to purify.

PMID- 30288461
TI  - Musical Instruments As Sensors.
AB  - The frequencies of notes made by a musical instrument are determined by the
      physical properties of the instrument. Consequently, by measuring the frequency
      of a note, one can infer information about the instrument's physical properties.
      In this work, we show that by modifying a musical instrument to contain a sample
      and analyzing the instrument's pitch, we can make precision measurements of the
      physical properties of the sample. We used the mbira, a 3000-year-old African
      musical instrument that consists of metal tines attached to a wooden board; these
      tines are plucked to play musical notes. By replacing the mbira's tines with bent
      steel tubing, filling the tubing with a sample, using a smartphone to record the
      sound while plucking the tubing, and measuring the frequency of the sound using a
      free software tool on our website, we can measure the density of the sample with
      a resolution of about 0.012 g/mL. Unlike existing tools for measuring density,
      the mbira sensor can be made and used by virtually anyone in the world. To
      demonstrate the mbira sensor's capabilities, we used it to successfully
      distinguish diethylene glycol and glycerol, two similar chemicals that are
      sometimes mistaken for each other in pharmaceutical manufacturing (leading to
      hundreds of deaths). We also show that consumers could use mbira sensors to
      detect counterfeit and adulterated medications (which represent around 10% of all
      medications in low- and middle-income countries). We expect that many other
      musical instruments can function as sensors and find important and lifesaving
      applications.

PMID- 30288460
TI  - Characterization of the Functional Changes in Mouse Gut Microbiome Associated
      with Increased Akkermansia muciniphila Population Modulated by Dietary Black
      Raspberries.
AB  - Gut microbiome plays an essential role in host health through host-gut microbiota
      metabolic interactions. Desirable modulation of beneficial gut bacteria, such as
      Akkermansia muciniphila, can confer health benefits by altering microbiome
      related metabolic profiles. The purpose of this study is to examine the effects
      of a black raspberry-rich diet to reshape the gut microbiome by selectively
      boosting A. muciniphila population in C57BL/6J mice. Remarkable changes of the
      mouse gut microbiome were revealed at both compositional and functional levels
      with an expected increase of A. muciniphila in concert with a profound impact on
      multiple gut microbiome-related functions, including vitamin biosynthesis,
      aromatic amino acid metabolism, carbohydrate metabolism, and oxidative stress.
      These functional alterations in the gut microbiome by an easily accessed freeze
      dried black raspberry-supplemented diet may provide novel insights on the
      improvement of human health via gut microbiome modulation.

PMID- 30288462
TI  - Synthesis of 2-Azaadamantan-6-one: A Missing Isomer.
AB  - 2-Azaadamantan-6-one and its Boc and ethylene ketal derivatives were synthesized
      from 9-oxo endo-bicyclo[3.3.1]non-6-ene-3-carboxylic acid. Similarly, the Cbz,
      Boc, and ethylene ketal derivatives of 2-azaadamantan-4-one were synthesized from
      endo-bicyclo[3.3.1]non-6-ene-3-carboxylic acid. Key steps were Curtius
      rearrangements to form benzyl carbamates, followed by spontaneous intramolecular
      attack of the carbamate nitrogen on transient bromonium ion or epoxide
      intermediates to effect ring closure to azaadamantane intermediates. The reaction
      sequence leading to 2-azaadamantan-6-one is consistent with the formation of a
      transient tetracyclic keto aziridine intermediate.

PMID- 30288463
TI  - Approximating Isotope Distributions of Biomolecule Fragments.
AB  - In mass spectrometry (MS)-based proteomics, protein and peptide sequences are
      determined by the isolation and subsequent fragmentation of precursor ions. When
      an isolation window captures only part of a precursor's isotopic distribution,
      the isotope distributions of the fragments depend on the subset of isolated
      precursor isotopes. Approximation of the expected isotope distributions of these
      fragments prior to sequence determination enables MS2 deisotoping, monoisotopic
      mass calculation, charge assignment of fragment peaks, and deconvolution of
      chimeric spectra. However, currently such methods do not exist, and precursor
      isotope distributions are often used as a proxy. Here, we present methods that
      approximate the isotope distribution of a biomolecule's fragment given its
      monoisotopic mass, the monoisotopic mass of its precursor, the set of isolated
      precursor isotopes, and optionally sulfur atom content. Our methods use either
      the Averagine model or splines, the latter of which have similar accuracy to the
      Averagine approach, but are 20 times faster to compute. Theoretical and
      approximated isotope distributions are consistent for fragments of in silico
      digested peptides. Furthermore, mass spectrometry experiments with the
      angiotensin I peptide and HeLa cell lysate demonstrate that the fragment methods
      match isotope peaks in MS2 spectra more accurately than the precursor Averagine
      approach. The algorithms for the approximation of fragment isotope distributions
      have been added to the OpenMS software library. By providing the means for
      analyzing fragment isotopic distributions, these methods will improve MS2 spectra
      interpretation.

PMID- 30288464
TI  - Improved Admixture Vaccine of Fentanyl and Heroin Hapten Immunoconjugates:
      Antinociceptive Evaluation of Fentanyl-Contaminated Heroin.
AB  - Fentanyl and its derivatives have become pervasive contaminants in the U.S.
      heroin supply. Previously, we reported a proof-of-concept vaccine designed to
      combat against heroin contaminated with fentanyl. Herein, we optimized the
      admixture vaccine and found that it surpassed the individual vaccines in every
      antinociceptive test, including a 10% fentanyl to heroin formulation. It is
      anticipated that other co-occurring drug abuse disorders may also be examined
      with admixture vaccines.

PMID- 30288465
TI  - Band-Like Charge Transport in Cs2AgBiBr6 and Mixed Antimony-Bismuth Cs2AgBi1-x Sb
      x Br6 Halide Double Perovskites.
AB  - Recently, halide double perovskites (HDPs), such as Cs2AgBiBr6, have been
      reported as promising nontoxic alternatives to lead halide perovskites. However,
      it remains unclear whether the charge-transport properties of these materials are
      as favorable as for lead-based perovskites. In this work, we study the mobilities
      of charges in Cs2AgBiBr6 and in mixed antimony-bismuth Cs2AgBi1-x Sb x Br6, in
      which the band gap is tunable from 2.0 to 1.6 eV. Using temperature-dependent
      time-resolved microwave conductivity techniques, we find that the mobility is
      proportional to T -p (with p ~ 1.5). Importantly, this indicates that phonon
      scattering is the dominant scattering mechanism determining the charge carrier
      mobility in these HDPs similar to the state-of-the-art lead-based perovskites.
      Finally, we show that wet chemical processing of Cs2AgBi1-x Sb x Br6 powders is a
      successful route to prepare thin films of these materials, which paves the way
      toward photovoltaic devices based on nontoxic HDPs with tunable band gaps.

PMID- 30288466
TI  - Covalent Rpn13-Binding Inhibitors for the Treatment of Ovarian Cancer.
AB  - Substitution of the m,p-chloro groups of bis-benzylidinepiperidone RA190 for p
      nitro, generating RA183, enhanced covalent drug binding to Cys88 of RPN13.
      Treatment of cancer cell lines with RA183 inhibited ubiquitin-mediated protein
      degradation, resulting in rapid accumulation of high-molecular-weight
      polyubiquitinated proteins, blockade of NFkappaB signaling, endoplasmic reticulum
      stress, an unfolded protein response, production of reactive oxygen species, and
      apoptotic cell death. High-grade ovarian cancer, triple-negative breast cancer,
      and multiple myeloma cell lines were particularly vulnerable to RA183. RA183
      stabilized a tetraubiquitin-linked firefly luciferase reporter protein in cancer
      cell lines and mice, demonstrating in vitro and in vivo proteasomal inhibition,
      respectively. However, RA183 was rapidly cleared from plasma, likely reflecting
      its rapid degradation to the active compound RA9, as seen in human liver
      microsomes. Intraperitoneal administration of RA183 inhibited proteasome function
      and orthotopic tumor growth in mice bearing human ovarian cancer model ES2-luc
      ascites or syngeneic ID8-luc tumor.

PMID- 30288469
TI  - Nuclear Receptors: Opening Up New Avenues of Pediatric Fatty Liver Research.

PMID- 30288467
TI  - Surface Patterning with SiO2@PNiPAm Core-Shell Particles.
AB  - Colloidal lithography is a cost-efficient method to produce large-scale
      nanostructured arrays on surfaces. Typically, colloidal particles are assembled
      into hexagonal close-packed monolayers at liquid interfaces and deposited onto a
      solid substrate. Many applications, however, require non close-packed monolayers,
      which are more difficult to fabricate. Preassembly at the oil/water interface
      provides non close-packed colloidal assemblies but these are difficult to
      transfer to a solid substrate without compromising the ordering due to capillary
      forces acting upon drying. Alternatively, plasma etching can reduce a close
      packed monolayer into a non close-packed arrangement, however, with limited
      interparticle distance and compromised particle shape. Here, we present a simple
      alternative approach toward non close-packed colloidal monolayers with tailored
      interparticle distance, high order, and retained spherical particle shape. We
      preassemble poly(N-isopropylacrylamide)-silica (SiO2@PNiPAm) core-shell particles
      at the air/water interface, transfer the interfacial spacer to a solid substrate,
      and use the polymer shell as a sacrificial layer that can be thermally removed to
      leave a non close-packed silica monolayer. The shell thickness, cross-linking
      density, and the phase behavior upon compression of these complex particles at
      the air/water interface provide parameters to precisely control the lattice
      spacing in these surface nanostructures. We achieve hexagonal non close-packed
      arrays of silica spheres with interparticle distances between 400 and 1280 nm, up
      to 8 times their diameter. The retained spherical shape is advantageous for
      surface nanostructuring, which we demonstrate by the fabrication of gold
      nanocrescent arrays via colloidal lithography and silicon nanopillar arrays via
      metal-assisted chemical etching.

PMID- 30288468
TI  - Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core
      Interface of HIV-1 Protease.
AB  - Four HIV-1 protease (PR) inhibitors, clinical inhibitors lopinavir and
      tipranavir, and two investigational compounds 4 and 5, were studied for their
      effect on the structure and activity of PR with drug-resistant mutation L76V
      (PRL76V). Compound 5 exhibited the best K i value of 1.9 nM for PRL76V, whereas
      the other three inhibitors had K i values of 4.5-7.6 nM, 2-3 orders of magnitude
      worse than for wild-type enzymes. Crystal structures showed only minor
      differences in interactions of inhibitors with PRL76V compared to wild-type
      complexes. The shorter side chain of Val76 in the mutant lost hydrophobic
      interactions with Lys45 and Ile47 in the flap, and with Asp30 and Thr74 in the
      protein core, consistent with decreased stability. Inhibitors forming additional
      polar interactions with the flaps or dimer interface of PRL76V were unable to
      compensate for the decrease in internal hydrophobic contacts. These structures
      provide insights for inhibitor design.

PMID- 30288471
TI  - Serum HBV RNA is a Potential Predictor of Hepatitis B Surface Antigen Reversion.

PMID- 30288470
TI  - Adherence to Nucleos(t)ide Analogue Therapies for Chronic Hepatitis B Infection:
      A Systematic Review and Meta-Analysis.
AB  - Successful treatment outcomes for chronic hepatitis B virus (HBV) infection
      requires high levels of adherence to treatment. We searched three databases and
      abstracts from two conferences up to January 2018 for studies reporting the
      proportion of patients who were adherent to HBV antiviral therapy and pooled data
      using random effects meta-analysis. We included 30 studies, providing data for
      23,823 patients. Overall, adherence to treatment was 74.6% (95% confidence
      interval [CI] 67.1%-82.1%). Adherence was similar in high-income settings (75.1%;
      95% CI, 65.4%-85.0%) and in low-income and middle-income settings (72.9%; 95% CI,
      57.8%-88.0%). Reported barriers to adherence included forgetting, limited
      understanding of the importance of adherence, and change to routine. Conclusion :
      There is a need to reinforce assessment and reporting of adherence as a routine
      part of HBV care and to assess the extent to which evidence-based interventions
      to improve adherence to medication for human immunodeficiency virus [HIV] and
      other chronic diseases are effective for HBV infection.

PMID- 30288472
TI  - Acute Kidney Injury in Patients Undergoing Chronic Hepatitis C Virus Treatment
      With Ledipasvir/Sofosbuvir.
AB  - Ledipasvir-sofosbuvir, a once-a-day, oral combination pill, was approved in 2014
      for the treatment of chronic hepatitis C infection. Initial trials did not
      comment on nephrotoxicity; however, recent data suggest a risk of acute kidney
      injury (AKI) with the use of the medication. We assessed the rates of AKI in
      patients undergoing ledipasvir-sofosbuvir in a large, urban tertiary care center.
      This single-center retrospective observation study included all patients
      undergoing therapy from October 1, 2014, to October 1, 2015. Rates of AKI,
      defined by more than a 0.3 mg/dL increase in serum creatinine level, were
      calculated. Patients were followed 12 weeks after therapy to assess for sustained
      viral response as well as to assess for improvement of AKI after completion of
      therapy, defined by less than 0.2 mg/dL above baseline serum creatinine. In
      total, 197 patients were included in the final analysis who had completed
      ledipasvir-sofosbuvir therapy and completed laboratory values. Among the patients
      treated, 38 (19%) had AKI during therapy. An additional 4 (2%) had AKI at the end
      of therapy. Of the 38 patients who experienced AKI, 20 (53%) had improvement in
      serum creatinine to less than 0.2 mg/dL above their baseline. When comparing for
      chronic kidney disease (CKD) stage, those with CKD I or II experienced AKI 17% of
      the time compared with 47% of the time in CKD III or worse (P = 0.005).
      Conclusion: AKI was seen in nearly one-fifth of our patients, and patients with
      CKD stage III or worse are at increased risk. Although ledipasvir-sofosbuvir is
      generally safe in the general population, close monitoring of renal function is
      recommended.

PMID- 30288473
TI  - Autoimmune Hepatitis During Ledipasvir/Sofosbuvir Treatment of Hepatitis C: A
      Case Report.
AB  - We report the case of a woman with chronic hepatitis C and idiopathic
      thrombocytopenic purpura (ITP) who developed autoimmune hepatitis (AIH) during
      antiviral therapy with ledipasvir (LDV)/sofosbuvir (SOF). The onset of acute
      hepatitis rose two weeks after starting treatment with LDV/SOF when HCV-RNA
      tested negative, suggesting a link between rapid HCV clearance and de novo
      autoimmune diseases. Conclusion: This case report proposes new immunologic
      scenarios in patients with hepatitis C virus (HCV) with laboratory or clinical
      signs of autoimmunity during direct-acting antiviral (DAA) therapy.

PMID- 30288475
TI  - Reactive Ductules Are Associated With Angiogenesis and Tumor Cell Proliferation
      in Pediatric Liver Cancer.
AB  - While reactive ductules (RDs) have been observed in viral hepatitis, biliary
      atresia, nonalcoholic fatty liver disease, and adult hepatocellular carcinoma
      (HCC), RDs in pediatric liver cancer remain uncharacterized. This study
      investigated the relationship of RDs with angiogenic paracrine factors, the
      extent of angiogenesis, and tumor cell proliferation in pediatric hepatoblastoma
      (HBL)/HCC livers. We quantified the extent of RDs and their expression of
      paracrine factors that include vascular endothelial growth factor (VEGF),
      vascular endothelial growth factor D (VEGFD), platelet-derived growth factor C,
      and angiopoietin 1 (ANGPT1). In addition, we performed immunohistochemical
      detection of the endothelial marker clusters of differentiation (CD)34 and the
      proliferation marker Ki67 followed by correlation analyses. In HBL, we found the
      percentage of RDs with Ki67 expression (% Ki67+ RDs) significantly correlated
      with intratumoral Ki67+ areas (r = 0.5138, P = 0.0349) and % ANGPT1+ RDs
      positively correlated with % Ki67+ RDs (r = 0.5851, P = 0.0136). In HCC, the high
      ANGPT1+ RDs group (i.e., cases with % ANGPT1+ RDs >=50) exhibited high
      intratumoral Ki67+ areas compared to the low ANGPT1+ RDs group. In the combined
      HBL and HCC liver tumor group, there was a positive association between %
      platelet-derived growth factor C+ RDs and intratumoral Ki67+ areas (r = 0.4712, P
      = 0.0099) and the high VEGFD+ RDs group (>=50%) exhibited a high number of
      peritumoral CD34+ vessels compared to the low VEGFD+ RDs group. Conclusion:
      Paracrine factor-expressing RDs are associated with angiogenesis and
      proliferation of pediatric liver tumors.

PMID- 30288474
TI  - Placebo-Controlled Randomized Trial of an Intestinal Bile Salt Transport
      Inhibitor for Pruritus in Alagille Syndrome.
AB  - Medically refractory, severe, cholestasis-induced pruritus in Alagille syndrome
      may be improved by surgical interruption of the enterohepatic circulation. This
      multicenter trial (NCT02057692) tested the hypothesis that the intestinal bile
      acid transport inhibitor maralixibat would similarly reduce pruritus in Alagille
      syndrome. Thirty-seven children with Alagille syndrome were randomly assigned to
      double-blinded administration of placebo, 70, 140, or 280 ug/kg/day of
      maralixibat for 13 weeks. Pruritus was assessed by caregiver (itch-reported
      outcome instrument [ItchRO]) and clinician report (range, 0-4 [severe]). Liver
      chemistries and serum bile acids were measured. The primary outcome was the
      change from baseline to week 13 in ItchRO relative to placebo. In the a priori
      first analysis of the primary efficacy endpoint, the mean adjusted difference
      between participants receiving 140 or 280 ug/kg/day and placebo was -0.47 (95%
      confidence interval [CI], -1.14, 0.20; P = 0.16). Statistically significant
      decreases were observed with doses of 70 and 140 ug/kg/day (mean adjusted
      difference, -0.89; 95% CI, -1.70, -0.08; P = 0.032; and mean adjusted difference,
      -0.91; 95% CI, -1.62, -0.19; P = 0.014) but not 280 ug/kg/day (mean adjusted
      difference, -0.04; 95% CI, -0.94, 0.86; P = 0.44) or all doses combined (mean
      adjusted difference, -0.61; 95% CI, -1.24, 0.20; P = 0.055). A 1-point reduction
      in pruritus was more common in maralixibat-treated versus placebo-treated
      participants (caregiver ItchRO, 65% versus 25%; P = 0.06; clinician score, 76%
      versus 25%; P = 0.01). There were no significant changes in liver chemistries or
      bile acids relative to placebo. Adverse and serious adverse events were similar
      between maralixibat and placebo. Conclusion: Although the prespecified primary
      analyses of ItchRO were not all statistically significant, the data suggest that
      maralixibat is safe and may reduce pruritus in Alagille syndrome.

PMID- 30288477
TI  - Among Patients With NAFLD, Treatment of Dyslipidemia Does Not Reduce
      Cardiovascular Mortality.
AB  - Dyslipidemia is one of the common risk factors for NAFLD and is associated with
      cardiovascular (CV) mortality, which is the most common cause of death in NAFLD.
      Lipid-lowering agents (LLAs) are used to reduce CV events in the general
      population. Our aim was to assess whether the use of LLAs in patients with NAFLD
      can reduce the risk of CV mortality. We used the third National Health and
      Nutrition Examination Survey mortality linked files. Mortality was determined
      from the National Death Index records through 2011. NAFLD was diagnosed by
      ultrasound after exclusion of other causes of liver disease. After inclusion and
      exclusion, the cohort consisted of 2,566 patients with NAFLD (45.8% < 45 years of
      age, 52.8% male, 75.4% white). Those who were taking LLAs were more likely to be
      older, non-Hispanic white, and had significantly higher rates of diabetes
      mellitus (DM), hyperlipidemia, hypertension, metabolic syndrome, and history of
      CV disease (CVD) (all P< 0.01). In our multivariate analysis, DM was an
      independent predictor of overall mortality (adjusted hazard ratio [aHR]: 1.79
      [95% confidence interval (CI): 1.40-2.30]) and CV mortality (aHR: 1.89 [95% CI:
      1.08-3.30]). History of CVD was associated with both overall (aHR: 2.03 [95% CI:
      1.57-2.63]) and CV mortality (aHR: 3.69 [95% CI: 2.23-6.08]). In contrast, the
      use of statins and other LLAs was not associated with reduction in overall (aHR =
      0.95 [95% CI: 0.37-2.44] and aHR = 1.43 [95% CI: 0.99-2.07]) and CV mortality
      (aHR = 1.20 [95% CI: 0.26-5.54] and aHR = 1.63 [95% CI: 0.70-3.76]). Conclusion:
      The use of statins and other LLAs did not reduce the increased risk of overall or
      CV mortality in NAFLD.

PMID- 30288476
TI  - Hepatic Nuclear Receptor Expression Associates with Features of Histology in
      Pediatric Nonalcoholic Fatty Liver Disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic
      liver disease in children and adults. This study examined the relationship
      between hepatic nuclear receptor (NR) expression and histologic features of
      NAFLD. Drugs targeting a variety of NRs for nonalcoholic steatohepatitis (NASH)
      are in clinical trials. Liver messenger RNA was isolated from 40 children (10-19
      years) undergoing end-of-treatment biopsy in the Treatment of NAFLD in Children
      (TONIC) trial. High-throughput quantitative polymerase chain reaction assayed NR
      messenger RNA. Cluster analysis was used to group 36 NRs, and NR levels were
      related to histologic measures of specific NAFLD features. Cluster analysis
      determined five groupings of NRs. Significant (P < 0.05) differential expressions
      of specific NRs associated with histologic measures include farnesoid X receptor
      alpha and retinoic acid receptor (RARbeta and RARbeta) for steatosis; estrogen
      receptor alpha (ERalpha) and peroxisome proliferator-activated receptor gamma 3
      (PPARgamma3) for hepatocellular ballooning; ER and PPARgamma2 for lobular
      inflammation; PPARalpha/delta/gamma1/gamma2, ERalpha, constitutive androstane
      receptor, chicken ovalbumin upstream promoter transcription factor 1, RARalpha,
      RARbeta1, retinoid X receptor, pregnane X receptor, thyroid hormone receptors
      alpha and beta, and nuclear receptor related-1 for fibrosis; and ERalpha and
      RARbeta/beta1/alpha for diagnosis of NASH. Conclusion: Differential expression of
      specific NRs correlates with histologic severity of specific NAFLD features.
      These NRs are pleiotropic transactivators regulating basal metabolic functions
      and inflammatory responses. Derangement of activity of these receptors in NAFLD
      provides a rationale for exploiting their ability with receptor-specific ligands
      to ameliorate NASH and its consequences.

PMID- 30288478
TI  - CEACAM1 Is Associated With the Suppression of Natural Killer Cell Function in
      Patients With Chronic Hepatitis C.
AB  - Natural killer cells (NK cells) play an essential role in the immunological
      mechanism underlying chronic hepatitis C (CHC). Impairment of NK cell function
      facilitates persistent infection with hepatitis C virus (HCV) and hepatocellular
      carcinogenesis. However, the mechanism by which NK cell activity is suppressed in
      CHC is not completely understood. In this study, we focused on carcinoembryonic
      antigen-related cell-adhesion molecule 1 (CEACAM1). CEACAM1 is thought to
      suppress NK cell function. We examined the effect of CEACAM1 on NK cell function
      in CHC. We investigated the function of CEACAM1 in vitro using Huh7.5.1 cells and
      the HCV-Japanese fulminant hepatitis (JFH)-1 strain. We analyzed serum CEACAM1
      level, NK cell function, and CEACAM1 messenger RNA (mRNA) level in human liver
      samples. Levels of CEACAM1 on the cell surface, CEACAM1 mRNA levels, and soluble
      CEACAM1 levels in supernatants were significantly higher in Huh7.5.1 cells
      infected with JFH-1 (Huh7.5.1/JFH-1 cells) than in Huh7.5.1 cells. Significantly
      higher NK cell cytotoxicity was observed toward K562 cells after coculture with
      CEACAM1 knockout Huh7.5.1/JFH-1 cells than after coculture with Huh7.5.1/JFH-1
      cells. CEACAM1 expression was induced by the HCV E2 glycoprotein in HCV
      infection. Significantly higher serum CEACAM1 levels were detected in patients
      with CHC compared with healthy subjects and patients who achieved sustained
      virological responses. The expression of CD107a on NK cells from patients with
      CHC was negatively correlated with serum CEACAM1 levels. Significantly higher
      levels of CEACAM1 mRNA were detected in HCV-infected livers compared with
      uninfected livers. Conclusion: CEACAM1 expression was induced in hepatocytes
      following HCV infection and decreased NK cell cytotoxicity. These results
      demonstrate a possible role for CEACAM1 in the pathogenesis of CHC and
      hepatocellular carcinoma progression.

PMID- 30288479
TI  - Micro RNA-4651 Serves as a Potential Biomarker for Prognosis When Selecting
      Hepatocellular Carcinoma Patients for Postoperative Adjuvant Transarterial
      Chemoembolization Therapy.
AB  - Our previous reports have shown that microRNA-4651 is a potential early
      diagnostic and prognostic marker for hepatocellular carcinoma. We aimed to
      investigate whether microRNA-4651 modified postoperative adjuvant transarterial
      chemoembolization (pa-TACE) to improve the prognosis of hepatocellular carcinoma.
      A hospital-based retrospective study, including 302 patients with advanced-stage
      hepatocellular carcinoma who received tumor resection or tumor resection plus pa
      TACE as an initial therapy, was conducted to assess the effects of microRNA-4651
      on pa-TACE treatment. MicroRNA-4651 expression in tumor tissues was tested using
      the TaqMan-PCR technique. The sensitivity of tumor cells to doxorubicin (an
      anticancer drug used in pa-TACE procedure) was analyzed by the half-maximal
      inhibitory concentration (IC50). Upregulated microRNA-4651 expression in tumor
      tissues can improve the therapeutic response of patients with hepatocellular
      carcinoma on pa-TACE (hazard ratios [95% confidence intervals] = 0.32 [0.22-0.46]
      for death risk and 0.39 [0.28-0.56] for tumor-recurrence risk, respectively), but
      downregulated expression cannot. Functional analyses-displayed microRNA-4651
      mimics decreased while its inhibitor increased the IC50 of tumor cells to
      doxorubicin (0.65 [0.61-0.69] versus 2.17 [1.98-2.37] uM). Cytochrome P450 2W1
      was shown as a possible target of microRNA-4651. Additionally, dysregulation of
      microRNA-4651 also affected the clinical pathological features of hepatocellular
      carcinoma and was an independent prognostic factor for this cancer. Conclusion:
      These results indicate that increasing microRNA-4651 expression may be beneficial
      for pa-TACE in improving hepatocellular carcinoma prognosis.

PMID- 30288480
TI  - Liver Disease Monitoring Practices After Hepatitis C Cure in the Underserved
      Population.
AB  - Recent hepatitis C virus (HCV) guidelines recommend disease monitoring and
      hepatocellular carcinoma (HCC) screening in patients with advanced fibrosis after
      a sustained virologic response (SVR) with direct-acting antiviral (DAA) therapy.
      However, data on practice patterns in this setting is lacking. We aimed to
      characterize disease monitoring and HCC screening practices post-SVR in an
      underserved HCV-infected cohort. Records of 192 patients who received DAA therapy
      at the San Francisco safety-net health care system between January 2014 and
      January 2016 with >=12 months of follow-up post-SVR were reviewed. Patient
      characteristics were median age 58 years, 61.5% men, 39.1% White (23.4% Black,
      16.7% Latino, 16.2% Asian), 78.1% English proficient, 48.9% intravenous drug use,
      53.2% alcohol use, and 41% advanced (F3 and F4) fibrosis (26.6% with
      decompensation, 11.4% with HCC). Median post-SVR follow-up time was 22 months. A
      higher proportion of patients with advanced fibrosis attended liver clinic visits
      (mean, 1.94 +/- 2.03 versus 1.12 +/- 1.09 visits; P = 0.014) and had liver
      imaging (41.4% versus 9.73%; P < 0.001) post-SVR, but there was no difference in
      alanine aminotransferase (ALT) testing (72.2% versus 66.4%; P = 0.40) compared to
      those without advanced fibrosis. However, 20% with advanced fibrosis had no HCC
      screening while 35% with no advanced fibrosis had liver imaging. Three patients
      with cirrhosis developed new HCC. Conclusion: Although the majority of patients
      with advanced fibrosis in this underserved cohort received post-SVR monitoring,
      gaps in HCC screening were identified and new cases of HCC occurred during a
      short follow-up. This highlights the importance of incorporating recently
      enhanced guidelines to optimize post-SVR monitoring, especially in difficult to
      engage populations.

PMID- 30288481
TI  - Serum Anti-Mullerian hormone and embryo morphokinetics detecting by time-lapse
      imaging: A comparison between the polycystic ovarian syndrome and tubal factor
      infertility.
AB  - Background: Anti-Mullerian hormone (AMH) is considered as a good marker for
      quantitative evaluation of ovarian response to the stimulation during assisted
      reproductive technology cycles. Objective: To evaluate the association between
      serum AMH level and embryo morphokinetics using time-lapse imaging and
      intracytoplasmic sperm injection (ICSI) outcomes in women with polycystic ovarian
      syndrome (PCOS). Materials and Methods: We evaluated a total of 547 embryos from
      100 women underwent ICSI cycles; 50 women with PCOS and 50 women with tubal
      factor infertility. Serum AMH level was measured in all participants. Time-laps
      records were annotated for time to pronuclear fading (tPNf), time to 2-8 cells
      (t2-t8), reverse cleavage, direct cleavage, and also for the presence of
      multinucleation. Results: AMH was negatively correlated with t5, t8, and the
      third cell cycle (p=0.02, p=0.02, and p=0.01; respectively) in PCOS group. AMH
      had no correlation with embryo kinetics in infertile women with tubal factor
      infertility. Moreover, AMH level is similar between embryos with and without
      direct cleavage as well as reverse cleavage and Multinucleation in both groups.
      The Receiver operating characteristic curves analyses indicated that AMH was not
      an accurate predictor of clinical pregnancy as well as a live birth (AUC=0.59
      [95% CI, 0.42-0.76]) in PCOS women. However, in the women with tubal factor
      infertility AMH showed a fair prediction value for clinical pregnancy (AUC=0.64
      [95% CI, 0.48-0.82]) along with the live birth (AUC=0.70 [95% CI, 0.55-0.85]).
      Conclusion: Some of the time-lapse embryo parameters may be related to the AMH
      concentration. However, AMH is not an accurate tool to predict the ICSI outcomes
      in PCOS women.

PMID- 30288482
TI  - The frequency of TP53 R72P and MDM2 309T>G polymorphisms in Iranian infertile men
      with spermatogenetic failure: A case-control study.
AB  - Background: Tumor protein p53 (TP53) is a tumor suppressor transcriptional
      regulator protein which plays a critical role in the spermatogenesis. One of the
      most important regulators of p53 is Murine double minute 2 (MDM2), which acts as
      a negative regulator of the p53 pathway. Based on the key role of p53 and MDM2 in
      germ cell apoptosis, polymorphisms that cause a change in their function might
      affect germ cell apoptosis and the risk of male infertility. Objective: This
      study was designed to examine associations of TP53 72 Arg>Pro (rs1042522), and
      MDM2 309 T>G (rs937283) polymorphisms with spermatogenetic failure in Iranian
      population. Materials and Methods: A case-control study was conducted with 150
      nonobstructive azoospermia or severe oligozoospermia and 150 fertile controls.
      The two polymorphisms, 72 Arg>Pro in TP53 and 309 T>G in MDM2, were genotyped
      using PCR-RFLP and ARMS-PCR respectively. Results: Our analyses revealed that the
      allele and genotype frequencies of the TP53 R72P polymorphism were not
      significantly different between the cases and controls (p=0.41, p=0.40
      respectively). Also, no significant differences were found in the allelic
      (p=0.46) and genotypic (p=0.78) distribution of MDM2 309 T>G polymorphism between
      patients and controls. Conclusion: The results of this study indicate that
      polymorphisms of TP53 and MDM2 genes are unlikely to contribute to the
      pathogenesis of male infertility with spermatogenetic failure.

PMID- 30288483
TI  - Antioxidant homeostasis is disturbed in fetuses with leptin-resistant genotypes:
      A cross-sectional study.
AB  - Background: Leptin resistance is associated with lower reproductive efficiency,
      with deficiencies in embryo viability and growth leading to low prolificacy and
      high incidence of intrauterine growth restriction. Objective: We aimed to
      investigate the underlying mechanisms of the leptin-resistance, evaluating the
      antioxidant homeostasis of leptin-resistant and lean swine fetuses. Materials and
      Methods: The study included 70 plasma samples from fetuses at day 62 of gestation
      (mid-pregnancy), from breeds with (Iberian breed; n=35) and without leptin
      resistance (25% Large White x 25% Landrace x 50% Pietrain; n=35). The antioxidant
      status of the plasma samples was determined by photoinduced chemiluminescence
      whilst systemic oxidative stress was assessed determining plasma hydrogen
      peroxide concentration by enzimoimmunoassay. Results: Plasma total antioxidant
      capacity was significantly lower in leptin-resistant fetuses (p=0.003), whilst
      systemic oxidative stress was increased (p=0.02). Conclusion: Our results
      indicate key differences in the antioxidant status in pregnancies affected by
      leptin resistance.

PMID- 30288484
TI  - The relationship between the expression levels of miR-135a and HOXA10 gene in the
      eutopic and ectopic endometrium.
AB  - Background: The study of microRNA expression can be effective in the diagnosing
      and treating different diseases. miR-135a is one of the most important micro
      ribonucleic acids involved in endometriosis. Among the genes that become the
      target of the miR-135a and are subjected to changes in the endometrium of
      patients with endometriosis is HOXA10 gene which is expressed in the endometrium
      in response to steroid hormones. Objective: The aim of this study was to evaluate
      the expression of miR-135a and its relationship with the level of HOXA10 gene
      expression in both endometrial ectopic and eutopic tissues in patients with
      endometriosis compared to the control samples. Materials and Methods: In this
      prospective case-control study, both case-eutopic and case-ectopic tissue samples
      were obtained from 17 women with endometriosis and the eutopic endometrial tissue
      was sampled from 17 women with normal endometrium as the control group. The
      gene's expression of miR-135a and HOXA10 were investigated using quantitative
      reverse transcription PCR (q-RT PCR). Results: A significant decrease in the
      expression of HOXA10 gene was detected in case-eutopic during the luteal phase
      compared to the control samples (p=0.001), while in the case-ectopic, the
      expression of this gene was increased (p=0.681) compared to the control samples.
      In addition, the expression miR-135a in the luteal phase showed a remarkable
      increase in the case-eutopic endometrial tissue (p=0.026) as well as a
      significant decrease in the case-ectopic endometrial tissue compared to the
      control samples (p=0.008). Conclusion: Considering the inverse relations between
      the over-expression of miR-135a and the reduction of HOXA10, it seems that miR
      135a may be applied as an endometrial diagnostic and therapeutic biomarker.

PMID- 30288485
TI  - Evaluation of specific germ cell genes expression in mouse embryonic stem cell
      derived germ cell like cells treated with bone morphogenetic protein 4 in vitro.
AB  - Background: Bone morphogenetic protein 4 (BMP4) is a significant signaling
      molecule that involves in initiating of differentiation and performs
      multifunctional effects on embryonic stem cells (ESCs) and embryos. Objective:
      The goal of the present study was to evaluate an in vitro differentiation model
      of mouse embryonic stem cells into germ cells, using BMP4. Materials and Methods:
      in this experimental study, we used Oct4-GFP mouse ESCs to form embryoid body
      (EB) aggregations for two days. Then, single cells from EB were cultured for four
      days with BMP4. Using MTT assay and gene expression levels for evaluation of Mvh
      and Riken by real-time RT-PCR of six concentrations, 12.5 ng/ ml BMP4 was
      determined as an optimized dose. Then, the expression level of Fkbp6, Mov10l1,
      4930432K21Rik, Tex13, Mvh, Scp3, Stra8, Oct4 were evaluated. Flow cytometry and
      immunostaning were used to confirm the findings of the real-time RT-PCR. Results:
      In the +BMP4 group, the genes encoding Riken (p<=0.001) and Mvh (p<=0.001) were
      found to be increased with significant differences compared with the control
      group. Mov10l1 (p=0.22), Tex13 (p=0.10), Fkbp6 (p=0.90), Scp3 (p=0.61) and Stra8
      (p=0.08) were up-regulated without significance differences compared with control
      group. Flow cytometry analysis showed that the mean number of Mvh-positive cells
      in the +BMP4 group was greater when compared with ESCs, -BMP4 and EB groups
      (p=0.03, p<=0.001, p=0.02, respectively). Conclusion: Down-regulation of Oct4,
      expression of germ cells genes and meiosis markers expression raise this
      hypothesis that ESCs were differentiated by BMP4, and may be introduced into the
      first meiosis as germ cell-like cells.

PMID- 30288486
TI  - The effect of crocin on testicular tissue and sperm parameters of mice offspring
      from mothers exposed to atrazine during pregnancy and lactation periods: An
      experimental study.
AB  - Background: Atrazine as a herbicide may affect the human's health. Crocin may
      protect atrazine-induced damages. Objective: The aim of this study was to
      evaluate the effects of atrazine on mice testicular tissue and sperm parameters
      and protective effects of Crocin on probably atrazine-induced damages. Materials
      and Methods: in this experimental study, 24 pregnant Balb/c mice were randomly
      divided to 4 groups: I: Atrazine (10 mg/kg), II: Atrazine-Crocin, III: Crocin
      (10mg/kg) and IV: Normal saline. Administrations were done daily by gavage during
      pregnancy and lactation. In the end, two male offspring were randomly selected
      from every mother and sacrificed respectively on 23 and 75 postnatal days. Then,
      their epididymides were removed for sperm parameters investigation and their
      testes were prepared to evaluate apoptosis by means of TUNEL technique. Results:
      The mean number of sperms in the atrazine group was lower compared to other
      groups and increased in the atrazine-crocin group compared with atrazine group
      significantly (p=0.001). Sperm abnormality was increased in the atrazine group
      compared with the normal saline group and decreased in the atrazine-crocin group
      compared with atrazine group significantly (p<=0.001). TUNEL-positive
      spermatogonia in 23 days old offspring increased significantly in the atrazine
      group compared with other groups (p=0.03). TUNEL-positive spermatogenic cells in
      75 days old offspring was significantly increased in the atrazine group compared
      with the saline group (p<=0.001). Conclusion: Atrazine exposure may lead to
      decrease the number of sperms, increase sperms abnormality, spermatogenic cell
      apoptosis and height of germinal epithelium. These complications may improve by
      crocin administration.

PMID- 30288487
TI  - Influence of body mass index and polycystic ovarian syndrome on ICSI/IVF
      treatment outcomes: A study conducted in Pakistani women.
AB  - Background: Obesity may establish a crucial barrier for effective fertility
      treatment in polycystic ovary syndrome (PCOS) females. Objective: To compare
      results of intra-cytoplasmic sperm injection (ICSI) in females with and without
      polycystic ovarian syndrome and further appraise the effect of obesity in PCOS
      females. Materials and Methods: A cross-sectional study from June 2015 to July
      2016 included non-PCOS and PCOS (recognized by Rotterdam criteria) females who
      underwent ICSI. The PCOS were further stratified into non-obese and Obese
      according to the South Asian criteria for body mass index. Results were
      categorized on the basis of beta-human chorionic gonadotropin (beta-hCG) and
      transvaginal scan into non-pregnant (beta-hCG <25 mIU/ml), preclinical abortion
      (beta-hCG >25 mIU/ml with no fetal cardiac activity) and clinical pregnancy (beta
      hCG >25 mIU/ml with fetal cardiac activity on transvaginal scan). In addition,
      reproductive outcomes; implantation rate, clinical pregnancy rate and miscarriage
      rate among obese and non-obese PCOS and non-PCOS patients were compared. Results:
      Our results revealed 38.5% clinical pregnancy rate in non-PCOs females, 23.8% in
      non-obese PCOS females whereas 26.4% in obese PCOS. Preclinical abortions were
      found to be highest (31.5%) in non-obese PCOS females and were the lowest (26.2%)
      in non-PCOS females. In non-PCOS group and non-obese PCOS females 35.4% and
      44.6%, respectively, failed to become pregnant. Conclusion: The success after
      ICSI in terms of number of clinical pregnancies was more in non-PCOS patients as
      compared to PCOS. Increase in body mass index reflected a negative impact on the
      reproductive outcome in PCOS patients.

PMID- 30288488
TI  - Comparison of pre-treatment with OCPs or estradiol valerate vs. no pre-treatment
      prior to GnRH antagonist used for IVF cycles: An RCT.
AB  - Background: Both oral contraceptive pills (OCPs) and estradiol valerate (E2) have
      been used to schedule a gonadotropin-releasing hormone antagonist in vitro
      fertilization (IVF) cycles. Since the suppression of follicle-stimulating hormone
      by OCPs can stay 5-7 days after stopping the pills, it seems that starting the
      gonadotropin-releasing hormone (GnRH) after 6 days of pre-treatment
      discontinuation may be important in IVF outcomes. Objective: The aim of the
      present study was to determine the number of mature oocyte and pregnancy rate of
      three pretreatment methods for fresh embryo transfer cycles. Materials and
      Methods: In this randomized controlled trial, two-hundred ten women (18-35 yr and
      less than 2 previous IVF attempts) undergoing IVF with the GnRH antagonist
      protocol were randomized to the OCP, E2, and no pretreatment arms. OCP group
      (n=53) received OCP (ethinyl estradiol30 MUg and levonorgestrel150 MUg), E2 group
      (n=63) received 4 mg/day oral E2 (17beta-E2) for 10 days from day 20 of the
      previous cycle and GnRH antagonist stimulation was started 6 days after the
      interruption of OCP and E2. The control group (n =70) did not receive any
      pretreatment. Results: No significant difference was observed in the mean number
      of the mature oocyte, endometrial thickness, and embryo quality. The pregnancy
      rate in E2 group was higher than the two other groups (42.9% vs 39.6% and 34.3%
      in OCP and control group, respectively), but the difference was not statistically
      significant (p=0.59). Conclusion: It seems OCP or E2 pretreatment could not
      improve the fresh IVF-embryo transfer outcomes.

PMID- 30288489
TI  - Editorial: Translational Control of APP Expression for Alzheimer Disease Therapy.

PMID- 30288490
TI  - Drastic Improvement of Air Stability in an n-Type Doped Naphthalene-Diimide
      Polymer by Thionation.
AB  - Organic thermoelectrics are attractive for the fabrication of flexible and cost
      effective thermoelectric generators (TEGs) for waste heat recovery, in particular
      by exploiting large-area printing of polymer conductors. Efficient TEGs require
      both p- and n-type conductors: so far, the air instability of polymer n-type
      conductors, which typically lose orders of magnitude in electrical conductivity
      (sigma) even for short exposure time to air, has impeded processing under ambient
      conditions. Here we tackle this problem in a relevant class of electron
      transporting, naphthalene-diimide copolymers, by substituting the imide oxygen
      with sulfur. n-type doping of the thionated copolymer gives rise to a higher
      sigma with respect to the non-thionated one, and most importantly, owing to a
      reduced energy level of the lowest-unoccupied molecular orbital, sigma is
      substantially stable over 16 h of air exposure. This result highlights the
      effectiveness of chemical tuning to improve air stability of n-type solution
      processable polymer conductors and shows a path toward ambient large-area
      manufacturing of efficient polymer TEGs.

PMID- 30288491
TI  - Risk-Reducing Options for Women with a Hereditary Breast Cancer Predisposition.
AB  - Genetic testing is now widely utilized to identify women with a hereditary
      predisposition for breast cancer. Women who carry mutations that increase breast
      cancer risk may consider three options to reduce risk: screening,
      chemoprevention, and prophylactic surgery. Yet, no randomized trials have
      specifically assessed the efficacy of these options in mutation carriers. In many
      developed countries, mammography is regarded as the optimal means of screening
      for breast cancer in the general population. However, breast MRI is a more
      sensitive screening tool, and for mutation carriers, any breast cancer screening
      strategy should incorporate screening with MRI. In randomized trials of women at
      high risk for developing breast cancer, chemoprevention reduces that risk, but it
      has not been shown to reduce mortality. Finally, observational studies suggest
      that, in mutation carriers, prophylactic surgery may reduce the risk of
      developing breast cancer by 90-95%. There are several prophylactic mastectomy
      procedures to choose from, and these are generally done in conjunction with
      breast reconstruction. In this article, we discuss management of women who carry
      mutations that have been associated with an increased breast cancer risk.
      Mutation carriers should be informed of the potential risks and benefits of the
      three available options to reduce breast cancer risk.

PMID- 30288492
TI  - QOL Evaluation of Nab-Paclitaxel and Docetaxel for Early Breast Cancer.
AB  - Objective: A previous randomized phase II study showed that neoadjuvant nab
      paclitaxel (nab-PTX) 100 mg/m2) was effective and well-tolerated in patients with
      HER2-negative early-stage breast cancer, compared with docetaxel (DTX). We
      evaluated patient outcomes in terms of the Functional Assessment of Cancer
      Therapy-Breast (FACT-B), as a measure of health-related quality of life (HRQoL).
      Materials and Methods: Stage I-III HER2-negative breast cancer patients from the
      previous study were included. They received either four cycles of nab-PTX (100
      mg/m2 days 1/8/15) every 4 weeks, or DTX (75 mg/m2 day 1) every 3 weeks, both
      followed by four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC).
      Patients completed a health-related quality-of-life questionnaire at baseline,
      after one and four cycles of taxanes, before administration of FEC, and after
      administration of one and four cycles of FEC. Results: Thirty-six eligible
      patients were enrolled. The baseline characteristics of the two groups were well
      balanced. FACT-B scores at baseline and after four cycles of taxanes were 115/108
      (DTX/nab-PTX) and 99/92, respectively. There were no significant differences
      between DTX and nab-PTX for FACT-B, FACT-B-Trial Outcome Index (FACT-B-TOI) and
      FACT-General. FACT-B and FACT-B TOI scores tended to decrease after one cycle and
      after four cycles of chemotherapy which did not recover to the baseline scores
      through the end of chemotherapy in each group. Conclusion: There were no
      significant safety differences between nab-PTX and DTX. HRQoL tended to decrease
      during taxane-based anticancer treatment, with no significant differences between
      the treatments. We suggest that the HRQoL questionnaire has limited ability to
      evaluate different chemotherapy schedules. Trial registration UMIN000009855. Nov
      20, 2012 registered.

PMID- 30288493
TI  - Evaluation of Breast Cancer (BC) Awareness among Female University Students in
      Zarqa University, Jordan.
AB  - Objective: The purposes of this study were to assess the level of Breast Cancer
      (BC) awareness of Jordanian female university students, measure their attitudes
      toward BC treatment, and compare the level of awareness and attitudes of students
      in the science and humanities faculties. Materials and Methods: The current study
      was cross-sectional and conducted among female students in Zarqa University in
      Jordan. Stratified random sampling and simple random sampling were employed to
      select the colleges and the students, respectively. The sample size was 326
      students. Data was collected and analyzed by self-administered questionnaire and
      SPSS version 23.0, respectively. Results: The number (proportion) of university
      students who had poor levels of awareness of BC, general knowledge about BC
      scale, knowledge about BC symptoms scale, and knowledge about risk factors of BC
      scale were was 270 (83%), 166 (51%), 182 (56%) and 292 (90%), respectively. Also,
      92 (28%) students and 234 (72%) students had high and medium attitudes toward BC
      treatment, respectively. There were significant differences between the
      humanities and science faculties students' awareness about BC and their attitudes
      toward BC treatment (p<0.05). Also, the results revealed that the students' main
      information source about BC was mainly health-care professionals, followed by
      internet and television. Conclusion: The current status of awareness of BC among
      Jordanian female students and their attitudes toward BC treatment are
      insufficient. Therefore, university compulsory courses need to be modified to
      include BC topics and promote awareness about BC.

PMID- 30288494
TI  - The Effect on Quality of Life and Body Image of Mastectomy Among Breast Cancer
      Survivors.
AB  - Objective: The objective of the present study was to determine effect on quality
      of life (QoL) and body image level following mastectomy among breast cancer (BC)
      survivors. Materials and Methods: In this descriptive study was carried out
      between February 2015 and December 2016 with 57 women with modified radical
      mastectomy and who in stage II and stage III. Data were collected using the socio
      demographic and body cathexis scale, Functional Assessment of Cancer Therapy
      Breast (FACT-B) to determine QoL. The study was carried out in home environment
      in which women lived. Results: The average age of the women was 49.34 years
      (ranged 28-78 years). Most of the women had undergone mastectomy for more than 6
      months.. Most of the women also received adjuvant chemotherapy and radiotherapy.
      The study showed that the mean FACT-B total score of the women was 68.47
      (SD=22.44), and the body image score was 121.61(SD=21.96). According to the
      results of linear regression analysis, except for the social/family well-being of
      FACT-B, positive correlations were calculated among the other sub-dimensions of
      FACT-B and the FACT-B total score and the body image total score respectively
      (beta=0.822, p=0.000). In the multiple linear regression model, there was medium
      correlation between education and work status with QoL, no correlation between
      QoL and other features of women. There was important positive relationship
      between body image with time after mastectomy and chemotherapy and no correlation
      between body image and other features of women. Conclusion: The results of this
      study showed that the mastectomy has a negative impact on body image and QoL of
      women and there was a strong positive correlation between body image and QoL.

PMID- 30288495
TI  - The Impact of Subtype Distribution in Inflammatory Breast Cancer Outcome.
AB  - Objective: Inflammatory breast cancer (IBC) has an unfavourable prognosis despite
      the advances made in the treatment of breast cancer. Our study aimed to define
      immunohistochemistry-based surrogate subtype distribution to determine whether
      the breast cancer subtype accompanied survival outcome differences in IBC.
      Materials and Methods: Medical records of female breast cancer patients with non
      metastatic inflammatory breast cancer admitted to our clinic between March 2000
      and December 2015 were retrospectively reviewed. Patient demographics, clinical
      and pathological feature of the primary tumour, adjuvant treatment options and
      survival data were analysed. Intrinsic breast cancer subtypes were defined
      according to ER, PR, HER-2 and ki-67 status. Results: We identified 129 non
      metastatic inflammatory breast cancer patients. Median follow-up was 73 months.
      10 (7.7%) were luminal A-like, 67 (51.9%) were luminal B-like, 37 (28.6%) were
      HER-2 positive, and 15 (11.6%) were triple negative (TNBC) by
      immunohistochemistry. There were no statistically significant differences between
      subtypes in terms of histological type, grade, tumour size and lymph node status.
      Median disease-free survival was 47 months (95% confidence interval [CI] 29.2
      82.6) and median overall survival was 75 months (95% CI 64.7-90.8). Triple
      negative breast cancer showed poorer outcome than other subgroups. Presence of
      TNBC disease was associated with poorer outcome compared to luminal A (HR: 0.19,
      95% CI 0.04-0.92, p: 0.039), luminal B (HR: 0.34, 95% CI 0.15-0.74, p: 0.007) and
      HER-2 positive subgroups (HR: 0.40, 95% CI 0.17-0.94, p:0.037). Luminal A
      patients had a trend to have a better overall survival which did not reach to a
      statistical significant difference. Conclusion: Our study put forth that IBC have
      a poor prognosis irrespective of breast cancer surrogate subtype distribution.
      Luminal A, the most frequent subtype of breast cancer was the least common in our
      IBC patient group. TNBC had the worst outcome when compared to other breast
      cancer subtypes.

PMID- 30288496
TI  - The Significance of Extent of Extracapsular Extension in Patients with T1-2 and
      N1 Breast Cancer.
AB  - Objective: The prognostic importance of extracapsular extension (ECE) in breast
      cancer is not yet clear, especially in patients with pathological T1-2 and N1
      (pT1-2N1) disease. We aimed to investigate whether the extent of ECE was an
      independent prognostic factor for survival outcomes in patients with pT1-2N1
      breast cancer. Materials and Methods: A total number of 131 patients with pT1-2N1
      breast cancer treated between 2009 and 2015 were retrospectively evaluated. A
      single pathologist re-analyzed the histologic examples of all cases. The extent
      of ECE was graded from 0 to 4. Results: There was a significant correlation
      between the number of lymph nodes involved and ECE grade (p=0.004). According to
      the univariate analysis, lymphovascular invasion (LVI) and ECE grade were the
      significant prognostic factors for overall survival (OS); age, number of
      metastatic lymph nodes, menopausal status, and ECE grade were the prognostic
      factors for disease-free survival (DFS). With a median follow-up of 46 months,
      grade 3-4 ECE seems to be notably associated with a shorter OS and DFS in
      multivariate analysis. The mean OS was 85 months for the patients with grade 0-2
      ECE vs 75 months for the patients with grade 3-4 ECE (p=0.003). The mean DFS was
      83 months for the patients with grade 0-3 ECE vs 68 months for the patients with
      grade 4 ECE (p=<0.0001). Conclusion: This research has shown that the extent of
      ECE is an important prognostic factor for survival in pT1-2N1 breast cancer
      patients and grade 3-4 ECE seems to be notably associated with a shorter OS and
      DFS.

PMID- 30288497
TI  - Impact of The Method of Diagnosis on The Stage of Breast Carcinoma.
AB  - Objective: Screening mammography is recommended to women at a certain age to
      achieve an early diagnosis. The purpose of this study is to find out how breast
      carcinoma was diagnosed and the impact of the method of diagnosis on the stage of
      the tumor. Materials and Methods: In this study, 903 operated breast cancer
      patients, between 2010-2016, in a large volume Marmara University Istanbul Pendik
      Education and Research Hospital were analyzed retrospectively. Patients
      presenting with clinical symptoms and those diagnosed with screening were
      investigated separately. The percentage of the patients diagnosed with symptoms
      and the impact of the method of diagnosis on the stage of the tumor was the
      primary outcome of the study. Results: 738 patients fulfilling inclusion criteria
      with complete clinical records were analyzed. 126 patients (17%) were in the age
      range of 19-39 years, while 32% (236 patients) were 40-50 and 51% (376 patients)
      were older than 50 years.485 patients (65.7%) were diagnosed with a mass in the
      breast, while 241 (32.6%) patients were diagnosed with screening with
      mammography. Twelve patients (1.7%) presented with nipple discharge. Median tumor
      sizes measured in the resected specimen were 22 mm, 21 mm, and 21 mm in patients
      diagnosed with a mass, screening, and nipple discharge respectively. The
      difference among the groups were not significant (p=0.460).Axillary lymph nodes
      were positive in 210 (43.3%) of patients presenting with a mass in the breast
      while 85 patients (35.3%) diagnosed with screening had metastatic lymph nodes in
      the axilla. Three patients presenting with nipple discharge had positive axillary
      lymph nodes (p=0.137). Conclusion: This study demonstrated that breast cancer
      screening programs in Turkey needs improvement and at the same time shows that
      screening with mammography after 40 years of age should be done annually despite
      Ministry of Health recommendations.

PMID- 30288498
TI  - Bilateral Inflammatory Pseudotumour of the Breast: A Case Report and Review of
      the Literature.
AB  - Inflammatory tumour (IPT) consists of spindle cells, mature plasma cells,
      histiocytes, lymphocytes and eosinophils. Most frequently presenting in the
      respiratory tract it can also affect other sites such as breast. This case was a
      73-year old woman presenting with a left breast lump, clinically indeterminate
      (P3), proven on biopsy to be IPT. Seven years later she returned with bilateral
      breast lumps and underwent triple assessment followed by wide excisions which
      confirmed the diagnosis of IPTs. Because it can be difficult to differentiate IPT
      from a low-grade spindle cell metaplastic breast carcinoma (SpCMBC) wide excision
      to achieve clear margins should be achieved to exclude malignancy.

PMID- 30288499
TI  - Dermatofibrosarcoma of The Breast - Case Report and Review of Literature.
AB  - Dermatofibrosarcoma protuberans is a rare form of soft tissue sarcoma that tends
      to invade and recur locally. The most common site of this disease is head, neck
      and extremities; however, the involvement of the breast has been reported. We
      present a case with a dermatofibrosarcoma of the breast that is composed of low
      grade spindle cells which are positive for CD43. She was treated by wide surgical
      excision followed by adjuvant external beam irradiation at a dose of 60 Gray.
      After a follow-up of 24 months, no local-regional or distant recurrence was
      detected.

PMID- 30288501
TI  - Reviewer List - 2018.

PMID- 30288500
TI  - Excisional Biopsies for Diagnosis and Treatment of Breast Lumps in Nigerian
      Women.

PMID- 30288503
TI  - Implications of Autophagy and Oxidative Stress in Trastuzumab-Mediated Cardiac
      Toxicities.
AB  - Trastuzumab, a humanized monoclonal antibody directed against human epidermal
      growth factor receptor 2 (HER2), remains the standard of care as part of adjuvant
      therapy for patients diagnosed with HER2-positive breast cancers. Despite high
      therapeutic efficacy, trastuzumab-based regimens can cause serious cardiotoxic
      side effects. Effective mitigation of cardiotoxic risk relies on thorough
      understanding of molecular mechanisms of cardiotoxicity induced by trastuzumab.
      Among the probable mechanisms responsible for trastuzumab-mediated
      cardiotoxicity, generation of free radicals causing oxidative stress has garnered
      notable attention in recent years. More recently, role of autophagy in
      trastuzumab-induced cardiomyopathy was explored. Trastuzumab-mediated HER2
      signaling dysregulation activated Erk/mTOR signaling cascade resulting in
      autophagy inhibition. Consequently, autophagy impairment leads to massive
      accumulation of damaged mitochondria and free radicals causing oxidative stress
      and toxicity in cardiomyocytes. This review will discuss recent advances in
      understanding the mechanism of oxidative stress and highlight the role of
      autophagy in trastuzumab-mediated cardiac dysfunctions.

PMID- 30288504
TI  - mCerebrum: A Mobile Sensing Software Platform for Development and Validation of
      Digital Biomarkers and Interventions.
AB  - : The development and validation studies of new multisensory biomarkers and
      sensor-triggered interventions requires collecting raw sensor data with
      associated labels in the natural field environment. Unlike platforms for
      traditional mHealth apps, a software platform for such studies needs to not only
      support high-rate data ingestion, but also share raw high-rate sensor data with
      researchers, while supporting high-rate sense-analyze-act functionality in real
      time. We present mCerebrum, a realization of such a platform, which supports high
      rate data collections from multiple sensors with realtime assessment of data
      quality. A scalable storage architecture (with near optimal performance) ensures
      quick response despite rapidly growing data volume. Micro-batching and efficient
      sharing of data among multiple source and sink apps allows reuse of computations
      to enable real-time computation of multiple biomarkers without saturating the CPU
      or memory. Finally, it has a reconfigurable scheduler which manages all prompts
      to participants that is burden- and context-aware. With a modular design
      currently spanning 23+ apps, mCerebrum provides a comprehensive ecosystem of
      system services and utility apps. The design of mCerebrum has evolved during its
      concurrent use in scientific field studies at ten sites spanning 106,806 person
      days. Evaluations show that compared with other platforms, mCerebrum's
      architecture and design choices support 1.5 times higher data rates and 4.3 times
      higher storage throughput, while causing 8.4 times lower CPU usage. CCS Concepts:
      * Human-centered computing -> Ubiquitous and mobile computing; Ubiquitous and
      mobile computing systems and tools; * Computer systems organization -> Embedded
      and cyber-physical systems. ACM Reference format: Syed Monowar Hossain, Timothy
      Hnat, Nazir Saleheen, Nusrat Jahan Nasrin, Joseph Noor, Bo-Jhang Ho, Tyson
      Condie, Mani Srivastava, and Santosh Kumar. 2017. mCerebrum: A Mobile Sensing
      Software Platform for Development and Validation of Digital Biomarkers and
      Interventions. In Proceedings of SenSys '17, Delft, Netherlands, November 6-8,
      2017, 14 pages.

PMID- 30288505
TI  - An electron-deficient nanosized polycyclic aromatic hydrocarbon with enhanced
      anion-pi interactions.
AB  - A super-pi-acidic nanosized polycyclic aromatic hydrocarbon with six imide groups
      at the corners was prepared from the pre-synthesized 7,8
      dichlorobenzo[ghi]perylenetriimide through a combination reaction of Ullmann-type
      and C-H transformation, which exhibited enhanced anion-pi interactions with
      various anions.

PMID- 30288506
TI  - A rare three-dimensional POM-based inorganic metal polymer bonded by CO2 with
      high catalytic performance for CO2 cycloaddition.
AB  - An exceedingly rare three-dimensional CO2-coordinated inorganic polyoxoanion was
      prepared by a hydrothermal synthesis reaction. The CO2 ligand connects with two
      Zn-epsilon-Keggin cores in a linear and symmetrical MU2-eta2o,o coordination
      pattern with a C[double bond, length as m-dash]O bond length of 1.099(112) A. The
      new compound reported here exhibits not only appealing structures but also high
      catalytic activity for the cycloaddition of carbon dioxide with epoxides.

PMID- 30288502
TI  - Using structural and functional brain imaging to uncover how the brain adapts to
      blindness.
AB  - Advances in neuroimaging technology have been instrumental in uncovering the
      dramatic neurological changes that result from blindness, as well as revealing
      the inner workings of the human brain. Specifically, modern imaging techniques
      enable us to examine how the brain adapts and "re-wires" itself as a result of
      changes in behavior, the environment, injury, or disease; a process referred to
      as neuroplasticity. Following an overview of commonly employed neuroimaging
      techniques, we discuss structural and functional neuroplastic brain changes
      associated with profound visual deprivation. In particular, we highlight how
      associated structural changes often occur within areas that process intact senses
      (such as hearing, touch, and smell) while functional changes tend to implicate
      areas of the brain normally ascribed to the processing of visual information.
      Evidence will primarily focus on profound blindness due to ocular cause, but
      related work in cerebral/cortical visual impairment (CVI) will also be discussed.
      The potential importance of these findings within the context of education and
      rehabilitation is proposed.

PMID- 30288507
TI  - Distinct roles of SNARE-mimicking lipopeptides during initial steps of membrane
      fusion.
AB  - A model system for membrane fusion, inspired by SNARE proteins and based on two
      complementary lipopeptides CPnE4 and CPnK4, has been recently developed. It
      consists of cholesterol (C), a poly(ethylene glycol) linker (Pn) and either a
      cationic peptide K4 (KIAALKE)4 or an anionic peptide E4 (EIAALEK)4. In this
      paper, fluorescence spectroscopy is used to decipher distinct but complementary
      roles of these lipopeptides during early stages of membrane fusion. Molecular
      evidence is provided that different distances of E4 in CPnE4 and K4 in CPnK4 from
      the bilayer represent an important mechanism, which enables fusion. Whereas E4 is
      exposed to the bulk and solely promotes membrane binding of CPnK4, K4 loops back
      to the lipid-water interface where it fulfills two distinct roles: it initiates
      bilayer contact by binding to CPnE4 containing bilayers; and it initiates fusion
      by modulating the bilayer properties. The interaction between CPnE4 and CPnK4 is
      severely down-regulated by binding of K4 to the bilayer and possible only if the
      lipopeptides approach each other as constituents of different bilayers. When the
      complementary lipopeptides are localized in the same bilayer, hetero-coiling is
      disabled. These data provide crucial insights as to how fusion is initiated and
      highlight the importance of both peptides in this process.

PMID- 30288508
TI  - Triphos-Fe dinitrogen and dinitrogen-hydride complexes: relevance to catalytic N2
      reductions.
AB  - The two electron reduction of iron complexes [(PRP2Cy)Fe(Cl)2] (R = Ph or tBu) 2a
      b afforded complexes [(PRP2Cy)Fe(N2)2] 4a-b. Protonation of 4a at the metal
      center and subsequent reduction to Fe(i)-H species lead to complex
      [(PPhP2Cy)Fe(N2)(H)2] 6avia a spontaneous disproportionation reaction. Complex 4a
      behaves as one of the most efficient monometallic Fe-catalysts reported to date
      for N2-to-N(SiMe3)3 functionalization under atmospheric pressure.

PMID- 30288509
TI  - A one-dimensional solid-state NMR approach for 14NH/14NH overtone correlation
      through 1H/1H mixing under fast MAS.
AB  - Homonuclear correlations are key to structural studies using solid-state NMR. In
      this contribution, using 14N overtone transition (OT) as a selective excitation
      approach, we propose a proton-detected one-dimensional (1D) 14NOT/14NOT/1H
      correlation solid-state NMR method mediated through 1H/1H mixing at fast magic
      angle spinning to achieve NH/NH proximities in naturally abundant samples. The
      proposed method is time efficient by a factor of ~7.5 in comparison to the
      existing fundamental 14N frequency-based three-dimensional (3D) 14N/14N/1H
      correlation method.

PMID- 30288510
TI  - Variation in the Yaa position of collagen peptides containing azaGlycine.
AB  - Herein, we report the systematic investigation of amino acid variation in the Yaa
      position of collagen peptides containing an adjacent azaGlycine residue. We
      demonstrate the reliability of azaGlycine as a glycine replacement and provide a
      sequence independent strategy for stabilizing the triple helical assembly of
      collagen peptides.

PMID- 30288511
TI  - Factors affecting microbial and physico-chemical pollutants in stormwater in a
      typical Chinese urban catchment.
AB  - An understanding of microbial pollution characteristics is needed for stormwater
      reuse and development of microorganism simulations in urban stormwater. This
      study investigated the discharge characteristics of faecal indicator bacteria
      (faecal coliforms) in urban runoff by field sampling both the underlying surfaces
      and the stormwater pipe outlet. Faecal coliform contamination in urban runoff was
      found to be frequent, and the highest instantaneous concentration reached 2.42 *
      106 MPN/100 ml. Faecal coliforms did not show a consistent first flush effect
      amongst the different surfaces sampled, and this was exacerbated under rainfall
      events with high intensity. PROMETHEE (Preference Ranking Organization Method for
      Enrichment Evaluation) and GAIA (Geometrical Analysis for Interactive Aid)
      analyses were further applied to explore the ranking of pollutants, the
      relationship among the pollutants, and the factors affecting the contamination in
      cases of multiple underlying surfaces, multiple pollutants and rainfall events.
      For the pollutants of suspended solids (SS), total phosphorus (TP) and chemical
      oxygen demand (COD), the road sample contamination was significantly higher than
      on the roof surfaces. No such trend in ranking of faecal coliforms was observed.
      Rainfall depth and intensity were found to have a significant influence on
      stormwater contamination by physico-chemical pollutants, while having a somewhat
      smaller influence on faecal coliform contamination. Faecal coliform contamination
      is closely associated with the index related to the antecedent dry period. The
      average temperature and average relative humidity also showed a positive
      relationship with faecal coliform contamination. The effects of antecedent dry
      period duration on contamination of physico-chemical pollutants and faecal
      coliform are completely opposite. Antecedent dry period duration was positively
      related to the contamination of physico-chemical pollutants, but negatively
      related to faecal coliform contamination. Therefore, three variables, i.e.,
      antecedent dry period duration, average temperature and average relative
      humidity, might be used to model the survival/die-off of faecal coliform during
      the antecedent dry period.

PMID- 30288512
TI  - Iridium-catalyzed direct asymmetric vinylogous allylic alkylation.
AB  - The catalytic asymmetric vinylogous allylic alkylation of alpha,beta-unsaturated
      lactones (including coumarins) was achieved with excellent regio- and
      enantioselectivity. Transformations of the product were carried out by means of
      the versatile terminal olefin and lactone moieties. The synthetic application of
      the present methodology was showcased by the asymmetric synthesis of an advanced
      synthetic Merck intermediate toward a new drug candidate.

PMID- 30288513
TI  - Machine learning and artificial neural network prediction of interfacial thermal
      resistance between graphene and hexagonal boron nitride.
AB  - High-performance thermal interface materials (TIMs) have attracted persistent
      attention for the design and development of miniaturized nanoelectronic devices;
      however, a large number of potential new materials exist to form these
      heterostructures and the explorations of their thermal properties are time
      consuming and expensive. In this work, we train several supervised machine
      learning (ML) and artificial neural network (ANN) models to predict the
      interfacial thermal resistance (R) between graphene and hexagonal boron-nitride
      (hBN) with only the knowledge of the system temperature, coupling strength
      between two layers, and in-plane tensile strains. The training data were obtained
      by high-throughput computations (HTCs) of R using classical molecular dynamics
      (MD) simulations. Four different ML models, i.e., linear regression, polynomial
      regression, decision tree and random forest, are explored. A pair of one dense
      layer ANNs and another pair of two dense layer deep neural networks (DNNs) are
      also investigated. It is reported that the DNN models provide better R prediction
      results compared to the ML models. The thermal property predictions using HTC and
      ML/ANN models are applicable to a wide range of materials and open up new
      perspectives in the explorations of TIMs.

PMID- 30288514
TI  - Detecting weak signals from interfaces by high accuracy phase-resolved SFG
      spectroscopy.
AB  - Much work over the last 25 years has demonstrated that the interface-specific,
      all-optical technique, vibrational sum frequency generation (v-SFG) spectroscopy,
      is often uniquely capable of characterizing the structure and dynamics of
      interfacial species. The desired information in such a measurement is the complex
      second order susceptibility which gives rise to the nonlinear response from
      interfacial molecules. The ability to detect molecular species yielding only
      small contributions to the susceptibility is meanwhile limited by the precision
      by which the spectral phase and amplitude can be determined. In this study we
      describe a new spectrometer design that offers unprecedented phase and amplitude
      accuracy for extended studies that involve multiple spectral acquisitions while
      modifying sample properties. The key to this significant improvement to the
      sensitivity of the technique is the combination of a full collinear beam geometry
      with broadband spectral sampling and the ability to simultaneously measure the
      complex sample and reference spectrum. We show that using this technique
      uncertainties in the reference phase and amplitude can be greatly reduced.
      Furthermore, we show that using balanced detection, the signal to noise ratio can
      be increased by one order of magnitude. The capabilities of the spectrometer are
      demonstrated by the isolation of a small isotropic surface signal from the bulk
      dominated nonlinear optical response of z-cut quartz. The achieved precision of
      our spectrometer enables measurements not currently feasible in v-SFG
      spectroscopy.

PMID- 30288515
TI  - Influence of compatible solute ectoine on distinct DNA structures: thermodynamic
      insights into molecular binding mechanisms and destabilization effects.
AB  - In nature, the cellular environment of DNA includes not only water and ions, but
      also other components and co-solutes, which can exert both stabilizing and
      destabilizing effects on particular oligonucleotide conformations. Among them,
      ectoine, known as an important osmoprotectant organic co-solute in a broad range
      of pharmaceutical products, turns out to be of particular relevance. In this
      article, we study the influence of ectoine on a short single-stranded DNA
      fragment and on double-stranded helical B-DNA in aqueous solution by means of
      atomistic molecular dynamics (MD) simulations in combination with molecular
      theories of solution. Our results demonstrate a conformation-dependent binding
      behavior of ectoine, which favors the unfolded state of DNA by a combination of
      electrostatic and dispersion interactions. In conjunction with the Kirkwood-Buff
      theory, we introduce a simple framework to compute the influence of ectoine on
      the DNA melting temperature. Our findings reveal a significant linear decrease of
      the melting temperature with increasing ectoine concentration, which is found to
      be in qualitative agreement with results from denaturation experiments. The
      outcomes of our computer simulations provide a detailed mechanistic rationale for
      the surprising destabilizing influence of ectoine on distinct DNA structures.

PMID- 30288516
TI  - A biodegradable fluorescent nanohybrid for photo-driven tumor diagnosis and tumor
      growth inhibition.
AB  - Specific targeting and phototriggered therapy in mouse model have recently
      emerged as the starting point of cancer theragnosis. Herein, we report a
      bioresponsive and degradable nanohybrid, a liposomal nanohybrid decorated with
      red emissive carbon dots, for localized tumor imaging and light-mediated tumor
      growth inhibition. Unsaturated carbon dots (C-dots) anchored to liposomes convert
      near-infrared (NIR) light into heat and also produce reactive oxygen species
      (ROS), demonstrating the capability of phototriggered cancer cell death and tumor
      regression. The photothermal and oxidative damage of breast tumor by the
      nonmetallic nanohybrid has also been demonstrated. Designed nanoparticles show
      excellent aqueous dispersibility, biocompatibility, light irradiated enhanced
      cellular uptake, release of reactive oxygen species, prolonged and specific tumor
      binding ability and good photothermal response (62  degrees C in 5 minutes). Safe
      and localized irradiation of 808 nm light demonstrates significant tumor growth
      inhibition and bioresponsive degradation of the fluorescent nanohybrid without
      affecting the surrounding healthy tissues.

PMID- 30288517
TI  - A G-triplex based molecular beacon for label-free fluorescence "turn-on"
      detection of bleomycin.
AB  - Since bleomycins (BLMs) play a prominent role in the clinical treatment of
      various cancers, the development of convenient and sensitive detection assays for
      BLM is of great significance in cancer therapy and related biological mechanism
      research. Here, taking advantage of the easily controllable and excitation of the
      G-triplex DNA structure, we reported a facile, label-free G-triplex based
      functional molecular beacon (G3MB) sensing system for fluorescence "turn-on"
      detection of BLM based on BLM-Fe(ii) mediated DNA strand scission. In the
      presence of BLM, the stable hairpin structure of G3MB undergoes an irreversible
      cleavage in the loop region that contains a 5'-GT-3' recognition site for BLM.
      The released G-tract DNA fragment self-assembles into a G-triplex-ThT complex
      showing a strong fluorescence. Owing to the effective locking of G-tracts in the
      stem of the G3MB and the specific DNA strand scission by BLM which is like a key
      for the release of G-tracts, the assay shows high sensitivity and selectivity
      with a detection limit of 0.2 nM. In addition, satisfactory results were obtained
      for the detection of BLM in human serum samples. Critically, the convenient "mix
      and-detect" protocol, fast response and no need for modifying DNA offered a
      potential application of the proposed strategy for BLM assay in biomedical and
      clinical studies.

PMID- 30288518
TI  - A sequence environment modulates the impact of methylation on the torsional
      rigidity of DNA.
AB  - We describe a potential molecular mechanism explaining how DNA methylation
      contributes to biological regulation. Using molecular dynamics together with a
      new torsional restraint, we identify the impact of methylation on DNA response to
      torsional stress. We observe that, depending on the sequence, DNA methylation
      hinders overwinding or underwinding molecular transitions.

PMID- 30288519
TI  - SERS-based quantification of albuminuria in the normal-to-mildly increased range.
AB  - The lack of an accurate point-of-care detection system for microalbuminuria
      represents an important unmet medical need that contributes to the morbidity and
      mortality of patients with kidney diseases. In this proof-of-concept study, we
      used SERS spectroscopy to detect urinary albumin concentrations in the normal-to
      mildly increased albuminuria range, a strategy that could be useful for the early
      diagnosis of renal impairment due to uncontrolled hypertension, cardiovascular
      disease or diabetes. We analyzed 27 urine samples by SERS, using iodide-modified
      silver nanoparticles and we could discriminate between groups with high and low
      albumin concentrations with an overall accuracy of 89%, 93% and 89%, using
      principal component analysis-linear discriminant analysis and cut-off values of
      3, 6 and 10 MUg mL-1 for urinary albumin concentrations, respectively. We
      achieved a detection limit of 3 MUg mL-1 for human serum albumin based on the
      1002 cm-1 SERS band, attributed to the ring breathing vibration of phenylalanine.
      Our detection limit is similar to that of the immunoturbidimetric assays and
      around one order of magnitude below the detection limit of urinary dipsticks used
      to detect microalbuminuria. We used principal least squares regression for
      building a spectral model for quantifying albumin. Using an independent
      prediction set, the R2 and root mean squared error of prediction between
      predicted and reference values of human serum albumin concentrations were 0.982
      and 2.82, respectively. Here, we show that direct SERS spectroscopy has the
      sensitivity required for detecting clinically relevant concentrations of urinary
      albumin, a strategy that could be used in the future for the point-of-care
      screening of microalbuminuria.

PMID- 30288520
TI  - Effect of surface coverage and chemistry on self-assembly of monolayer protected
      gold nanoparticles: a molecular dynamics simulation study.
AB  - Gold nanoparticles (AuNP) are being used in a variety of applications ranging
      from drug delivery systems to nano-coolants. The structure and surface properties
      of AuNP can be manipulated using coatings of thiols, carrying different charges.
      Different densities of surface coverage can result in the formation of different
      structures. A molecular basis to quantify the interactions between AuNP covered
      with different densities (20, 60 and 100%) of surface coverage and various thiol
      chains (neutral, cationic and anionic) is obtained using potential of mean force
      (PMF) calculations. Further self-assembly simulations were performed to study the
      formation of aggregates/dispersed solutions with different densities of surface
      coverage (20, 40, 60, 80 and 100%). It is found that neutral coatings of all
      surface coverage densities studied, and charged coatings (anionic and cationic)
      of less than 60% surface coverage density result in the formation of aggregates.
      The aggregation and dispersion of AuNPs is explained in terms of an interplay
      between van der Waals and electrostatic forces. The results obtained are in good
      agreement with the data available in the literature and suggest that aggregation
      behaviour can be controlled by modifying the surface coverage and chemistry.

PMID- 30288521
TI  - Asymmetric fluorination of indanone-2-carboxylates using a polystyrene-supported
      diphenylamine-linked bis(oxazoline) complex.
AB  - A highly enantioselective fluorination of indanone-2-carboxylates catalyzed by a
      polystyrene-supported diphenylamine-linked bis(oxazoline) (PS-box)-Cu(OTf)2
      complex has been developed in a continuous flow system. The supported complex
      exhibited extremely efficient catalytic performance with high activity, affording
      the corresponding products in excellent yields (up to 99% yield) with excellent
      enantioselectivities (up to 99% ee) and more than 4000 turnover number (TON).

PMID- 30288522
TI  - Palladium(ii)-mediated rapid 11C-cyanation of (hetero)arylborons.
AB  - A palladium(ii)-mediated rapid 11C-cyanation of (hetero)arylborons with
      [11C]NH4CN/NH3 has been developed using bench-stable and readily available
      reagents. The method showed excellent functional-group tolerance, and allowed the
      highly efficient synthesis of a wide range of [11C]cyanoarenes, including PET
      tracers for aromatase imaging. A mechanistic study of the 11C-cyanation suggests
      the instantaneous formation of a mono[11C]cyanopalladium(ii) complex that reacts
      smoothly with arylborons.

PMID- 30288523
TI  - MoS2 monolayers on Si and SiO2 nanocone arrays: influences of 3D dielectric
      material refractive index on 2D MoS2 optical absorption.
AB  - Heterostructures enable the control of transport and recombination of charge
      carriers, which are either injected through electrodes, or created by light
      illumination. Instead of full 2D-material-heterostructures in device
      applications, using hybrid heterostructures consisting of 2D and 3D materials is
      an alternative approach to take advantage of the unique physical properties of 2D
      materials. In addition, 3D dielectric nanostructures exhibit useful optical
      properties such as broadband omnidirectional antireflection effects and strongly
      concentrated light near the surface. In this work, the optical properties of 2D
      MoS2 monolayers conformally coated on 3D Si-based nanocone (NC) arrays are
      investigated. Numerical calculations show that the absorption in MoS2 monolayers
      on SiO2 NC is significantly enhanced, compared with that for MoS2 monolayers on
      Si NC. The weak light confinement in low refractive index SiO2 NC leads to
      greater absorption in the MoS2 monolayers. The measured photoluminescence and
      Raman intensities of the MoS2 monolayers on SiO2 NC are much greater than those
      on Si NC, which supports the calculation results. This work demonstrates that 2D
      MoS2-3D Si nano-heterostructures are promising candidates for use in high
      performance integrated optoelectronic device applications.

PMID- 30288524
TI  - Poly(ethylene glycol)-poly-l-glutamate complexed with polyethyleneimine
      polyglycine for highly efficient gene delivery in vitro and in vivo.
AB  - To improve gene transfection efficiency in vitro and in vivo, we first grafted
      polyglycine (PGly) onto branched polyethyleneimine (PEI) (molecular weight MW 25
      kDa) to obtain a novel gene vector PGly-PEI (PPG), before complexing it with
      poly(ethylene glycol)-poly-l-glutamate (PEG-PLG) for adjusting the charge density
      of PEI. We named the resulting nano-polyplex PG/PPG. The PPGs demonstrated
      improved gene transfection efficiency after grafting with polyglycine, and the
      efficiency could be further increased with the introduction of PEG-PLG. The
      PG/PPG exhibited not only excellent DNA and siRNA transfection capacity in
      various cell lines including HeLa, CHO, HepG2, MCF7 and Huh7, but also reduced
      cytotoxicity compared with PEI. Besides, PG/PPG induced a higher degree of cell
      apoptosis when mixed genes of pKH3-rev-casp-3 plasmid and siBcl2 were used rather
      than either of them. Furthermore, PG/PPG was highly resistant to serum, which led
      to enhanced in vivo red fluorescent protein (RFP) expression in HeLa tumors.
      These results suggested that PG/PPG is a promising gene carrier for highly
      efficient gene delivery.

PMID- 30288525
TI  - Epitaxial growth of Ni(OH)2 nanoclusters on MoS2 nanosheets for enhanced alkaline
      hydrogen evolution reaction.
AB  - Constructing heterostructures is an effective strategy for designing efficient
      electrocatalysts. MoS2 is a star catalyst for hydrogen evolution reaction (HER)
      in acidic media; however, the alkaline HER activity is deficient due to the
      sluggish water dissociation process. Herein, Ni(OH)2/MoS2 heterostructures with
      Ni(OH)2 nanoclusters epitaxially decorated on the surface of MoS2 are synthesized
      towards the alkaline HER. As compared with MoS2, the epitaxial Ni(OH)2/MoS2
      heterostructures show significantly enhanced HER activity in 1 M KOH, and the
      overpotential is decreased by nearly 150 mV to reach a current density of 10 mA
      cm-2. The substantial increase in turnover frequency (TOF) demonstrates that the
      intrinsic activity is greatly improved after the incorporation of Ni(OH)2
      nanoclusters. The presence of Ni(OH)2 nanoclusters would provide additional water
      dissociation sites while MoS2 is ready for the adsorption and combination of the
      generated H*, and this so-called synergistic effect eventually induces
      significantly enhanced alkaline HER kinetics. Besides, the electron transfer from
      Ni(OH)2 to MoS2 increases the proton affinity of MoS2. The present results
      describe an interesting case of an atomic-scale electrochemically inert material
      promoted HER process, and would open a new avenue into designing efficient hetero
      nanostructures towards electrocatalytic applications.

PMID- 30288531
TI  - Sterol-modified PEG lipids: alteration of the bilayer anchoring moiety has an
      unexpected effect on liposome circulation.
AB  - We synthesized and characterized two novel sterol-anchored polyethylene glycols
      (PEG) as potential alternatives to conventional phosphatidylethanolamine-PEGs.
      Liposomes containing the dicholesterol anchored PEG at 5 mole percent exhibit
      canonical PEGgylated-liposome behaviors including retention of encapsulated small
      molecules, low serum protein adsorption, and reduced cellular uptake yet they do
      not exhibit long circulation.

PMID- 30288532
TI  - Creep dynamics of athermal amorphous materials: a mesoscopic approach.
AB  - Yield stress fluids display complex dynamics, in particular when driven into the
      transient regime between the solid and the flowing state. Inspired by creep
      experiments on dense amorphous materials, we implement mesoscale elasto-plastic
      descriptions to analyze such transient dynamics in athermal systems. Both our
      mean-field and space-dependent approaches consistently reproduce the typical
      experimental strain rate responses to different applied steps in stress.
      Moreover, they allow us to understand basic processes involved in the strain rate
      slowing down (creep) and the strain rate acceleration (fluidization) phases. The
      fluidization time increases in a power-law fashion as the applied external stress
      approaches a static yield stress. This stress value is related to the stress over
      shoot in shear start-up experiments, and it is known to depend on sample
      preparation and age. By calculating correlations of the accumulated plasticity in
      the spatially resolved model, we reveal different modes of cooperative motion
      during the creep dynamics.

PMID- 30288533
TI  - Formal reductive addition of acetonitrile to aldehydes and ketones.
AB  - An efficient and highly productive rhodium-catalyzed method for the synthesis of
      nitriles employing aldehydes or ketones, methyl cyanoacetate, water and carbon
      monoxide as starting materials has been developed. Simple rhodium chloride
      without any ligands can be used. The fine tuning of the substrate can lead to the
      activity higher than 5000 TON.

PMID- 30288534
TI  - Synthetic hydrogels formed by thiol-ene crosslinking of vinyl sulfone-functional
      poly(methyl vinyl ether-alt-maleic acid) with alpha,omega-dithio
      polyethyleneglycol.
AB  - Polymer hydrogels formed by rapid thiol-ene coupling of macromolecular gel
      formers can offer access to versatile new matrices. This paper describes the
      efficient synthesis of cysteamine vinyl sulfone (CVS) trifluoroacetate, and its
      incorporation into poly(methyl vinyl ether-alt-maleic anhydride) (PMMAn) to form
      a series of CVS-functionalized poly(methyl vinyl ether-alt-maleic acid) polymers
      (PMM-CVSx) containing 10 to 30 mol% pendant vinyl sulfone groups. Aqueous
      mixtures of these PMM-CVS and a dithiol crosslinker, alpha,omega-dithio
      polyethyleneglycol (HS-PEG-SH, Mn = 1 kDa), gelled through crosslinking by
      Michael addition within seconds to minutes, depending on pH, degree of
      functionalization, and polymer loading. Gelation efficiency, Young's modulus,
      equilibrium swelling and hydrolytic stability are described, and step-wise
      hydrogel post-functionalization with a small molecule thiol, cysteamine, was
      demonstrated. Cytocompatibility of these crosslinked hydrogels towards entrapped
      3T3 fibroblasts was confirmed using a live/dead fluorescence assay.

PMID- 30288535
TI  - Influence of the donor unit on the rectification ratio in tunnel junctions based
      on donor-acceptor SAMs using PTM units as acceptors.
AB  - Dyads formed by an electron donor unit (D) covalently linked to an electron
      acceptor (A) by an organic bridge are promising materials as molecular
      rectifiers. Very recently, we have reported the charge transport measurements
      across self-assembled monolayers (SAMs) of two D-A systems consisting of the
      ferrocene (Fc) electron-donor linked to a polychlorotriphenylmethane (PTM)
      electron-acceptor in its non-radical (SAM 1) and radical (SAM 2) forms.
      Interestingly, we observed that the non-radical SAM 1 showed rectification
      behavior of 2 orders of magnitude higher than its radical analogue dyad 2. In
      order to study the influence of the donor unit on the transport properties, we
      report herein the synthesis and characterization of two new D-A SAMs in which the
      electron-donor Fc unit is replaced by a tetrathiafulvalene (TTF) moiety linked to
      the PTM unit in its non-radical (SAM 3) and radical (SAM 4) forms. The observed
      decrease in the rectification ratio and increased current density for TTF-PTM
      based SAMs 3 and 4 in comparison to Fc-PTM based SAMs 1 and 2 are explained,
      supported by theoretical calculations, by significant changes in the electronic
      and supramolecular structures.

PMID- 30288536
TI  - Polyamidoxime chain length drives emergent metal-binding phenomena.
AB  - Emergence is complex behavior arising from the interactions of many simple
      constituents that do not display such behavior independently. Polyamidoxime (PAO)
      uranium adsorbents show such phenomena, as recent works articulate that the
      polymer binds uranium differently than the monomeric constituents. In order to
      investigate the origins of this emergent uranium-binding behavior, we synthesized
      a series of amidoxime polymers with low polydispersity and small molecules with
      lengths ranging from 1 to 125 repeat units. Following immersion in a uranyl
      containing solution, the local, intermediate, and macroscopic structures were
      investigated by X-ray absorption fine structure (XAFS) spectroscopy, small angle
      neutron scattering (SANS), and dynamic light scattering (DLS). Fits of the
      extended XAFS (EXAFS) region revealed a progressive change in uranium
      coordination environment as a function of polymer molecular weight, identifying
      chain length as a driving force in emergent metal binding and resolving the
      controversy over how amidoxime adsorbents bind uranium.

PMID- 30288537
TI  - Transition metal-free coupling of terminal alkynes and hypervalent iodine-based
      alkyne-transfer reagents to access unsymmetrical 1,3-diynes.
AB  - A variety of unsymmetrical 1,3-diynes can easily be accessed in good yields under
      catalyst- and transition metal-free conditions by reacting terminal alkynes with
      hypervalent iodine-based electrophilic alkyne-transfer reagents.

PMID- 30288538
TI  - UPS and UV spectroscopies combined to position the energy levels of TiO2 anatase
      and rutile nanopowders.
AB  - An accurate experimental determination of electronic structures in semi-conductor
      nanopowders is a challenging task. We propose here to combine UPS and UV-Vis
      spectroscopies in order to get the full description of the electronic band
      alignment of powder samples, TiO2 rutile and anatase. For UPS measurements, two
      preparation methods, namely the dropping method and electrophoretic deposition,
      were used to prepare layers of titania powders on a conducting substrate, ITO or
      Ag. Both methods lead to comparable results, with a quantitative description of
      the energy levels from the valence band. Combining these results with the UV-Vis
      spectra of the same powders enables the determination of the absolute position of
      the valence band maximum and the conduction band minimum. Combined UPS-UV-Vis
      spectroscopy provides a better insight into the properties of a powdered material
      which can differ from single crystal model systems. It can also be used to
      predict the electronic transfer in mixed phase systems during photocatalytic
      processes.

PMID- 30288539
TI  - Transition-metal-free access to 2-aminopyridine derivatives from 2-fluoropyridine
      and acetamidine hydrochloride.
AB  - Under catalyst-free conditions, an efficient method for the synthesis of 2
      aminopyridine derivatives through the nucleophilic substitution and hydrolysis of
      2-fluoropyridine and acetamidine hydrochloride has been developed. This amination
      uses inexpensive acetamidine hydrochloride as the ammonia source and has the
      advantages of a high yield, high chemoselectivity and wide substrate
      adaptability. The results suggest that other N-heterocycles containing fluorine
      substituents can also complete the reaction via these reaction conditions and
      yield the target products.

PMID- 30288540
TI  - Electric-field control of non-volatile 180 degrees  switching of the
      unidirectional anisotropy field in a multiferroic heterostructure.
AB  - We investigate the room-temperature, electric-field-mediated, non-volatile 180
      degrees  switching of the unidirectional anisotropy field in an
      IrMn/CoFeB/Ta/Pb(Mg1/3Nb2/3)O3-PbTiO3 heterostructure. The variation in exchange
      bias under different electric fields appears clearly in the magnetic hysteresis
      loops. The remnant magnetization as a function of electric field, as determined
      by static magnetic measurements, exhibits a non-volatile behavior, which is
      consistent with the results of the ferromagnetic resonance field as a function of
      electric field. Moreover, the measured ferromagnetic resonance shows that the
      uniaxial magnetic anisotropy field is non-volatile and the unidirectional
      anisotropy field undergoes 180 degrees  switching that can be acquired and
      separated distinctly. This result is attributed to the piezo-strain effect. The
      electric-field-mediated non-volatile 180 degrees  switching of the unidirectional
      anisotropy field paves the way for sensors and other spintronic devices.

PMID- 30288541
TI  - A DFT analysis of the ground and charge-transfer excited states of Sc3N@Ih-C80
      fullerene coupled with metal-free and zinc-phthalocyanine.
AB  - Endohedral metallofullerenes and phthalocyanine derivatives are recognized as
      excellent active materials in organic photovoltaics (OPVs). The tri-metallic
      nitride endohedral C80 fullerenes have greater absorption coefficients in the
      visible region and electron-accepting abilities similar to C60, which can allow
      for higher efficiencies in OPV devices. In this work, we have investigated the
      ground and charge transfer excited states of two co-facial donor-acceptor (D-A)
      molecular conjugates formed by the non-covalent coupling of trimetallic nitride
      endohedral fullerene (Sc3N@Ih-C80) with metal-free (H2Pc) and zinc-phthalocyanine
      (ZnPc) chromophores using DFT calculations. The charge transfer (CT) excitation
      energies are calculated using the perturbative delta-SCF method that enforces
      orthogonality between the ground and excited states. The binding energies
      calculated using the PBE and DFT-D3 methods indicate that the dispersion effects
      play an important role in the stabilization of these complexes. The ground state
      dipole moment of the Sc3N@C80-H2Pc dyad is much larger than that of Sc3N@C80
      ZnPc, but this is reversed in the excited state where the dipole moment of
      Sc3N@C80-ZnPc increases significantly. The lowest few excitation energies in the
      gas phase for the two complexes are very close, in the range of 1.51-2.66 eV for
      Sc3N@C80-ZnPc and 1.51-2.71 eV for the Sc3N@C80-H2Pc complex. However, the lower
      ionization potential and lower exciton binding energy make the Sc3N@C80-ZnPc dyad
      a better candidate for OPVs as compared to the Sc3N@C80-H2Pc dyad.

PMID- 30288542
TI  - Non-toxic cyanide sources and cyanating agents.
AB  - The present review gives an overview over non-toxic cyanation agents and cyanide
      sources used in the synthesis of structurally diverse products containing the
      nitrile function. Nucleophilic as well as electrophilic agents/systems that
      transfer the entire CN-group were taken in consideration. Reactions in which a
      preexisting carbon functionality is transformed into a nitrile function by
      addition of nitrogen are however not covered here.

PMID- 30288543
TI  - Low catalytic activity of the Cu(ii)-binding motif (Xxx-Zzz-His; ATCUN) in
      reactive oxygen species production and inhibition by the Cu(i)-chelator BCS.
AB  - The catalytic redox activity of Cu(ii) bound to the motif NH2-Xxx-Zzz-His (ATCUN)
      with ascorbate and H2O2/O2 is very low and can be stopped via Cu(i)-chelation.
      This impacts its application as an artificial Cu-enzyme to degrade biomolecules
      via production of reactive oxygen species in a Cu(i)-chelator rich environment
      like the cytosol.

PMID- 30288544
TI  - Genetic and Genome Analyses Reveal Genetically Distinct Populations of the Bee
      Pathogen Nosema ceranae from Thailand.
AB  - The recent global decline in Western honeybee (Apis mellifera) populations is of
      great concern for pollination and honey production worldwide. Declining honeybee
      populations are frequently infected by the microsporidian pathogen Nosema
      ceranae. This species was originally described in the Asiatic honeybee (Apis
      cerana), and its identification in global A. mellifera hives could result from a
      recent host transfer. Recent genome studies have found that global populations of
      this parasite are polyploid and that humans may have fueled their global
      expansion. To better understand N. ceranae biology, we investigated its genetic
      diversity within part of their native range (Thailand) and among different hosts
      (A. mellifera, A. cerana) using both PCR and genome-based methods. We find that
      Thai N. ceranae populations share many SNPs with other global populations and
      appear to be clonal. However, in stark contrast with previous studies, we found
      that these populations also carry many SNPs not found elsewhere, indicating that
      these populations have evolved in their current geographic location for some
      time. Our genome analyses also indicate the potential presence of diploidy within
      Thai populations of N. ceranae.

PMID- 30288545
TI  - Fungal, Bacterial, and Archaeal Diversity in Soils Beneath Native and Introduced
      Plants in Fiji, South Pacific.
AB  - The Fiji Islands is an archipelago of more than 330 islands located in the
      tropics of the South Pacific Ocean. Microbial diversity and biogeography in this
      region is still not understood. Here, we present the first molecular
      characterization of fungal, bacterial, and archaeal communities in soils from
      different habitats within the largest Fijian island, Viti Levu. Soil samples were
      collected from under native vegetation in maritime-, forest-, stream-, grassland
      , and casuarina-dominated habitats, as well as from under the introduced
      agricultural crops sugarcane, cassava, pine, and mahogany. Soil microbial
      diversity was analyzed through MiSeq amplicon sequencing of 16S (for
      prokaryotes), ITS, LSU ribosomal DNA (for fungi). Prokaryotic communities were
      dominated by Proteobacteria (~ 25%), Acidobacteria (~ 19%), and Actinobacteria (~
      17%), and there were no indicator species associated with particular habitats.
      ITS and LSU were congruent in beta-diversity patterns of fungi, and fungal
      communities were dominated by Ascomycota (~ 57-64%), followed by Basidiomycota (~
      20-23%) and Mucoromycota (~ 10%) according to ITS, or Chytridiomycota (~ 9%)
      according to LSU. Indicator species analysis of fungi found statistical
      associations of Cenococcum, Wilcoxina, and Rhizopogon to Pinus caribaea. We
      hypothesize these obligate biotrophic fungi were co-introduced with their host
      plant. Entoloma was statistically associated with grassland soils, and Fusarium
      and Lecythophora with soils under cassava. Observed richness varied from 65
      (casuarina) to 404 OTUs (cassava) for fungi according to ITS region, and from
      1268 (pine) to 2931 OTUs (cassava) for bacteria and archaea. A major finding of
      this research is that nearly 25% of the fungal OTUs are poorly classified,
      indicative of novel biodiversity in this region. This preliminary survey provides
      important baseline data on fungal, bacterial, and archaeal diversity and
      biogeography in the Fiji Islands.

PMID- 30288548
TI  - Predatory journals: a major threat in orthopaedic research.
AB  - Predatory publishing is a major threat to contemporary publishing, as it offers
      'to unaware scientist's', a quick open-access publication against fees without
      peer-review procedures.. Lack of peer-review leads to unethical practices, as
      plagiarism, publication of unscientific falsified data, and even unsafe clinical
      practices. As these journals threaten the credibility of academic publishing,
      significant work has been done from many scientific teams, in the last years, in
      establishing discriminating criteria between predatory and legitimate publishing.
      In the present review, we include mechanisms used by predatory editors to
      convince eager researchers to submit to their journals. We also provide useful
      links giving information about potential predatory journals and publishers, as
      well as scholarly writing. Joining the efforts of different scientific
      disciplines which compiled "green" lists with journals in their field, we
      conducted a "green" list with genuine orthopaedic research journals based on the
      directory of open-access journals (DOAJ) and Thomson Reuters journal citation
      reports. Ninety-six legitimate orthopaedic journals were identified based on the
      Thomson Reuters journal citation reports. One hundred thirty hits were found on
      the DOAJ site using the keywords "orthopaedics, orthopedics, sports medicine,
      musculoskeletal, trauma, traumatology, osteoarthritis, osteoporosis, cartilage,
      bone, hand, shoulder, knee, hip, foot, wound." Twenty-one journals on the DOAJ
      site occurred overlapping with keywords. Researchers and clinicians in the field
      of orthopaedics are advised to use all available tools in order to recognize
      predatory practices and avoid publishing in predatory journals.

PMID- 30288546
TI  - Trichostatin A, a histone deacetylase inhibitor, induces synergistic cytotoxicity
      with chemotherapy via suppression of Raf/MEK/ERK pathway in urothelial carcinoma.
AB  - In this study, we aimed to investigate the antitumor effects of trichostatin A
      (TSA), an antifungal antibiotic that inhibits histone deacetylase (HDAC) family
      of enzymes, alone or in combination with anyone of the three chemotherapeutic
      agents (cisplatin, gemcitabine, and doxorubicin) for the treatment of human
      urothelial carcinoma (UC). Two high-grade human UC cell lines (T24 and NTUB1)
      were used. Cytotoxicity and apoptosis were assessed by MTT assay and flow
      cytometry, respectively. The expression of phospho-c-Raf, phospho-MEK1/2, and
      phospho-ERK1/2 was measured by western blotting. ERK siRNA knockdown and the
      specific MEK inhibitor U0126 were used to examine the role of Raf/MEK/ERK
      signaling pathway in combined cytotoxicity of TSA and chemotherapy. TSA co
      treatment with any one of the three chemotherapeutic agents induced synergistic
      cytotoxicity (combination index < 1) and concomitantly suppressed
      chemotherapeutic drug-induced activation of Raf-MEK-ERK pathway. Combination of
      ERK siRNA knockdown and treatment with the specific MEK inhibitor (U0126)
      enhanced the cytotoxic effects of the chemotherapy on UC cells. These
      observations were confirmed in a xenograft nude mouse model. Moreover, activated
      Raf/MEK/ERK pathway was observed in human bladder UC specimens from patients with
      chemoresistant status. In conclusion, TSA elicits a synergistic cytotoxic
      response in combination with chemotherapy via targeting the Raf/MEK/ERK pathway.
      TSA elicits synergistic cytotoxic response in combination with three DNA-damaging
      drugs (cisplatin, gemcitabine, and doxorubicin). Activated Raf/MEK/ERK pathway is
      involved in chemoresistant mechanism of UC. Combining chemotherapeutic agents
      with HDAC inhibitor (TSA) or with targeting Raf/MEK/ERK pathway is promising to
      circumvent chemoresistance in UCs.

PMID- 30288549
TI  - Correction to: Model of Mercury Flux Associated with Volcanic Activity.
AB  - The original version of this article contained a mistake in Fig. 2. The country
      names have been missed in the figure legend along with the X-axis. The corrected
      figure is given below.

PMID- 30288550
TI  - Head skeleton malformations in zebrafish (Danio rerio) to assess adverse effects
      of mixtures of compounds.
AB  - The EU-EuroMix project adopted the strategy of the European Food Safety Authority
      (EFSA) for cumulative risk assessment, which limits the number of chemicals to
      consider in a mixture to those that induce a specific toxicological phenotype.
      These so-called cumulative assessment groups (CAGs) are refined at several
      levels, including the target organ and specific phenotype. Here, we explore the
      zebrafish embryo as a test model for quantitative evaluation in one such CAG,
      skeletal malformations, through exposure to test compounds 0-120 hpf and alcian
      blue cartilage staining at 120 hpf, focusing on the head skeleton. Reference
      compounds cyproconazole, flusilazole, metam, and thiram induced distinctive
      phenotypes in the head skeleton between the triazoles and dithiocarbamates. Of
      many evaluated parameters, the Meckel's-palatoquadrate (M-PQ) angle was selected
      for further assessment, based on the best combination of a small confidence
      interval, an intermediate maximal effect size and a gentle slope of the dose
      response curve with cyproconazole and metam. Additional test compounds included
      in the CAG skeletal malformations database were tested for M-PQ effects, and this
      set was supplemented with compounds associated with craniofacial malformations or
      cleft palate to accommodate otherwise organized databases. This additional set
      included hexaconazole, all-trans-retinoic acid, AM580, CD3254, maneb,
      pyrimethanil, imidacloprid, pirimiphos-methyl, 2,4-dinitrophenol, 5-fluorouracil,
      17alpha-ethynylestradiol (EE2), ethanol, 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), PCB 126, methylmercury, boric acid, and MEHP. Most of these compounds
      produced a dose-response for M-PQ effects. Application of the assay in mixture
      testing was provided by combined exposure to cyproconazole and TCDD through the
      isobole method, supporting that in this case the combined effect can be modeled
      through concentration addition.

PMID- 30288551
TI  - Single-phase CT angiography: collateral grade is independent of scan weighting.
AB  - PURPOSE: Collateral grading may vary on single-phase CTA (sCTA) depending on
      whether the CTA is arterial (A), arteriovenous (AV), or venous (V) weighted. We
      studied the impact of sCTA weighting on collateral grading using the Tan, MAAS,
      and Menon methods, and their ability to predict infarct and clinical outcome
      hypothesizing that AV-weighted sCTA should better predict these outcomes.
      METHODS: Multicenter retrospective analysis of 212 patients undergoing baseline
      CTP/sCTA. sCTA weighting was determined by comparing ICA to torcula AV ratios
      with those from concomitant CTP time-density curves at peak arterial or venous
      contrast attenuation. A generalized linear mixed model investigated the
      predictive value for infarct volume or 90-day mRS of the three collateral scores
      stratified by sCTA weighting and adjusting for age, sex, clot burden score (CBS),
      and NIHSS. Bayesian information criterion (BIC) differences were calculated
      between the null and fitted models. RESULTS: Mean age, baseline median NIHSS,
      ASPECTS, and onset to treatment time were 69.89 +/- 14.45, 13 (6-18), 10 (8-10),
      and 128 (66-181) minutes. sCTA scans were AV-weighted in 137/212 (65%) and A
      weighted in 73 (34%). No association was demonstrated between sCTA weighting,
      hospital site, and sCTA technique. All collateral scores were related to infarct
      volume irrespective of sCTA weighting, with greatest fit with the regional
      leptomeningeal score (BIC 18.29, p = 0.0001). No association was shown between
      sCTA weighting, collateral grade, and clinical outcome. CONCLUSION: sCTA
      weighting did not significantly impact collateral grade using three common
      collateral scores or their ability to predict final infarct.

PMID- 30288552
TI  - Nulliplex-branch, a TERMINAL FLOWER 1 ortholog, controls plant growth habit in
      cotton.
AB  - KEY MESSAGE: Nulliplex-branch (nb) mutants in cotton display a specific
      architecture. The gene responsible for the nb phenotype was identified, and its
      modulation mode was further studied. Plant architecture is an important agronomic
      factor influencing various traits such as yield and variety adaptability in crop
      plants. Cotton (Gossypium) simultaneously displays monopodial and sympodial
      growth. Nulliplex-branch (nb) mutants showing determinate sympodial shoots have
      been reported in both G. hirsutum (Ghnb) and G. barbadense (Gbnb). In this study,
      the gene responsible for the nb phenotype was identified. GhNB and GbNB were
      found to be allelic loci and are TERMINAL FLOWER 1 orthologs on the Dt subgenome,
      though the At copies remain native. Sequencing and association analyses
      identified four (Gh-nb1-Gh-nb4) and one (Gb-nb1) type of point mutation in the
      coding sequences of Ghnb and Gbnb, respectively. The NB gene was mainly expressed
      in the root and shoot apex, and expression rhythms were also observed in these
      tissues, suggesting that the expression of the NB gene could be regulated by
      photoperiod. Constitutive overexpression of GhNB suppresses the differentiation
      of the reproductive shoots. Knockout of both copies of GhNB caused the main and
      lateral shoots to terminate in flowers, which is a more determinate architecture
      than that of the nb mutants and implies that its function might be dosage
      dependent. A protein lipid overlay assay indicated that the amino acid
      substitutions in Gh-nb1 and Gb-nb1 weaken the ligand-binding activity of the NB
      protein in vitro. These findings suggest that the NB gene plays crucial roles in
      regulating the determinacy of shoots, and the modulation of this gene should
      constitute an effective crop improvement approach through adjusting the growth
      habit of cotton.

PMID- 30288553
TI  - Genomic selection efficiency and a priori estimation of accuracy in a structured
      dent maize panel.
AB  - KEY MESSAGE: Population structure affects genomic selection efficiency as well as
      the ability to forecast accuracy using standard GBLUP. Genomic prediction models
      usually assume that the individuals used for calibration belong to the same
      population as those to be predicted. Most of the a priori indicators of
      precision, such as the coefficient of determination (CD), were derived from those
      same models. But genetic structure is a common feature in plant species, and it
      may impact genomic selection efficiency and the ability to forecast prediction
      accuracy. We investigated the impact of genetic structure in a dent maize panel
      ("Amaizing Dent") using different scenarios including within- or across-group
      predictions. For a given training set size, the best accuracies were achieved
      when predicting individuals using a model calibrated on the same genetic group.
      Nevertheless, a diverse training set representing all the groups had a certain
      predictive efficiency for all the validation sets, and adding extra-group
      individuals was almost always beneficial. It underlines the potential of such a
      generic training set for dent maize genomic selection applications. Alternative
      prediction models, taking genetic structure explicitly into account, did not
      improve the prediction accuracy compared to GBLUP. We also investigated the
      ability of different indicators of precision to forecast accuracy in the within-
      or across-group scenarios. There was a global encouraging trend of the CD to
      differentiate scenarios, although there were specific combinations of target
      populations and traits where the efficiency of this indicator proved to be null.
      One hypothesis to explain such erratic performances is the impact of genetic
      structure through group-specific allele diversity at QTLs rather than group
      specific allele effects.

PMID- 30288554
TI  - Lymphomatoid granulomatosis mimicking cancer and sarcoidosis.
AB  - Two cases of misdiagnoses of lymphomatoid granulomatosis are discussed here.
      Lymphomatoid granulomatosis is an Epstein-Barr virus-associated
      lymphoproliferative disorder with aggressive behavior. Due to its rarity and many
      presentations, delay in diagnosis and treatment is common. Its histological
      features including large atypical B-cells, T cell predominance, angiocentricity,
      necrosis, and evidence of EBV-positive cells should elicit the diagnosis of
      lymphomatoid granulomatosis. The settings that are described here have not yet
      been described in the literature.

PMID- 30288555
TI  - Results of Duodenopancreatic Reoperations in Multiple Endocrine Neoplasia Type 1.
AB  - BACKGROUND: To evaluate the outcome of duodenopancreatic reoperations in patients
      with multiple endocrine neoplasia type 1 (MEN1). METHODS: MEN1 patients who
      underwent reoperations for duodenopancreatic neuroendocrine neoplasms (dpNENs)
      were retrieved from a prospective database and retrospectively analyzed. RESULTS:
      Twelve of 101 MEN1 patients underwent up to three reoperations, resulting in a
      total of 18 reoperations for dpNEN recurrence. Patients initially underwent
      either formal pancreatic resections (n = 7), enucleations (n = 3), or duodenotomy
      with lymphadenectomy for either NF-pNEN (seven patients), Zollinger-Ellison
      syndrome (ZES, three patients), organic hyperinsulinism (one patient) or VIPoma
      (one patient). Six patients had malignant dpNENs with lymph node (n = 5) and/or
      liver metastases (n = 2). The indication of reoperations was NF-pNEN (five
      patients), ZES (five patients), organic hyperinsulinism (one patient), and
      recurrent VIPoma (one patient). Median time to first reoperation was 67.5 (range
      6-251) months. Five patients required a second duodenopancreatic reoperation for
      60-384 months after initial surgery, and one patient underwent a third
      reoperation after 249 months. The rate of complications (Clavien-Dindo >=3) was
      28%. Four patients required completion pancreatectomy. Six patients developed
      pancreoprivic diabetes. After a median follow-up of 18 (6-34) years after initial
      surgery, ten of 12 patients are alive, one died of metastatic pancreatic VIPoma,
      and one died of metastatic thymic NEN. CONCLUSION: Reoperations are frequently
      necessary for dpNEN in MEN1 patients, but are not associated with an increased
      perioperative morbidity in specialized centers. Organ-sparing resections should
      be preferred as initial duodenopancreatic procedures to maintain pancreatic
      function and avoid completion pancreatectomy.

PMID- 30288556
TI  - C-reactive protein as a biomarker of severe H1N1 influenza.
AB  - BACKGROUND: C-reactive protein (CRP) is an acute-phase reactant downstream of the
      pro-inflammatory cytokines released during influenza infection. However, the role
      of this inflammatory marker in influenza severity and complications is yet to be
      elucidated. OBJECTIVES: We aim to systematically review and evaluate the levels
      of CRP in severe and non-severe H1N1 influenza cases and assess its utility as a
      biomarker in predicting the severity of infection. METHODS: We conducted a
      comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of Print,
      Embase and Embase Classic to identify human studies reporting measurements of CRP
      levels in patients infected with H1N1 influenza at various levels of disease
      severity. RESULTS: Our search identified ten studies eligible for inclusion in
      this systematic review. The results of the data analysis show that the average
      CRP levels upon diagnosis were significantly higher (P < 0.05) in patients who
      developed severe H1N1 influenza compared to their counterparts with a no severe
      disease. Furthermore, levels of CRP were associated with the degree of H1N1
      severity. Subjects with H1N1-related pneumonia and patients who were hospitalized
      or died of the disease complications, respectively, had 1.4- and 2.5-fold
      significantly higher CRP levels (P < 0.05) than those with no severe disease
      outcome. CONCLUSION: CRP levels have been consistently shown to be significantly
      higher in H1N1 influenza patients who develop a severe disease outcome. The
      resuts of the present study suggest that serum CRP can be employed-in combination
      with other biomarkers-to predict the complications of H1N1 influenza.

PMID- 30288557
TI  - Unidirectional monosynaptic connections from auditory areas to the primary visual
      cortex in the marmoset monkey.
AB  - Until the late twentieth century, it was believed that different sensory
      modalities were processed by largely independent pathways in the primate cortex,
      with cross-modal integration only occurring in specialized polysensory areas.
      This model was challenged by the finding that the peripheral representation of
      the primary visual cortex (V1) receives monosynaptic connections from areas of
      the auditory cortex in the macaque. However, auditory projections to V1 have not
      been reported in other primates. We investigated the existence of direct
      interconnections between V1 and auditory areas in the marmoset, a New World
      monkey. Labelled neurons in auditory cortex were observed following 4 out of 10
      retrograde tracer injections involving V1. These projections to V1 originated in
      the caudal subdivisions of auditory cortex (primary auditory cortex, caudal belt
      and parabelt areas), and targeted parts of V1 that represent parafoveal and
      peripheral vision. Injections near the representation of the vertical meridian of
      the visual field labelled few or no cells in auditory cortex. We also placed 8
      retrograde tracer injections involving core, belt and parabelt auditory areas,
      none of which revealed direct projections from V1. These results confirm the
      existence of a direct, nonreciprocal projection from auditory areas to V1 in a
      different primate species, which has evolved separately from the macaque for over
      30 million years. The essential similarity of these observations between marmoset
      and macaque indicate that early-stage audiovisual integration is a shared
      characteristic of primate sensory processing.

PMID- 30288558
TI  - Rheumatoid pulmonary nodules: clinical and imaging features compared with
      malignancy.
AB  - OBJECTIVES: The objective of this study was to identify clinical and imaging
      features that distinguish rheumatoid lung nodules from malignancy. METHODS: We
      conducted a retrospective review of 73 rheumatoid patients with histologically
      proven rheumatoid and malignant lung nodules encountered at Mayo Clinic,
      Rochester, MN (2001-2016). Medical records and imaging were reviewed including a
      retrospective blinded review of CT and PET/CT studies. RESULTS: The study cohort
      had a mean age of 67 +/- 11 years (range 45-86) including 44 (60%) women, 82%
      with a smoking history, 38% with subcutaneous rheumatoid nodules, and 78% with
      rheumatoid factor seropositivity. Subjects with rheumatoid lung nodules compared
      to malignancy were younger (59 +/- 12 vs 71 +/- 9 years, p < 0.001), more likely
      to manifest subcutaneous rheumatoid nodules (73% vs 20%, p < 0.001) and
      rheumatoid factor seropositivity (93% vs 68%, p = 0.034) but a history of smoking
      was common in both groups (p = 0.36). CT features more commonly associated with
      rheumatoid lung nodules compared to malignancy included multiplicity, smooth
      border, cavitation, satellite nodules, pleural contact, and a subpleural rind of
      soft tissue. Optimal sensitivity (77%) and specificity (92%) (AUC 0.85, CI 0.75
      0.94) for rheumatoid lung nodule were obtained with >= 3 CT findings (>= 4
      nodules, peripheral location, cavitation, satellite nodules, smooth border, and
      subpleural rind). Key 18FDG-PET/CT features included low-level metabolism (SUVmax
      2.7 +/- 2 vs 7.2 +/- 4.8, p = 0.007) and lack of 18F-fluorodeoxyglucose (FDG)
      avid draining lymph nodes. CONCLUSION: Rheumatoid lung nodules have distinct CT
      and PET/CT features compared to malignancy. Patients with rheumatoid lung nodules
      are younger and more likely to manifest subcutaneous rheumatoid nodules and
      seropositivity. KEY POINTS: * Rheumatoid lung nodules have distinct clinical and
      imaging features compared to lung malignancy. * CT features of rheumatoid lung
      nodules include multiplicity, cavitation, satellite nodules, smooth border,
      peripheral location, and subpleural rind. * Key PET/CT features include low-level
      metabolism and lack of FDG-avid draining lymph nodes.

PMID- 30288560
TI  - The current status of MRI in the pre-operative assessment of intramedullary
      conventional appendicular osteosarcoma.
AB  - Osteosarcoma is the commonest primary malignant bone tumour in children and
      adolescents, the majority of cases being conventional intra-medullary high-grade
      tumours affecting the appendicular skeleton. Treatment is typically with a
      combination of neo-adjuvant chemotherapy, tumour resection with limb
      reconstruction and post-operative chemotherapy. The current article reviews the
      role of magnetic resonance imaging (MRI) in the pre-operative assessment of high
      grade central conventional osteosarcoma.

PMID- 30288559
TI  - Cognitive-behavioral therapy effects on alerting network activity and effective
      connectivity in panic disorder.
AB  - Given the particular relevance of arousal and alerting in panic disorder (PD),
      here the alerting network was investigated (1) contrasting patients with PD and
      healthy controls, (2) as a function of anxiety sensitivity constituting a
      dimensional measure of panic-related anxiety, and (3) as a possible correlate of
      treatment response. Using functional magnetic resonance imaging (fMRI), 45 out
      patients with PD (f = 34) and 51 matched healthy controls were investigated for
      brain activation patterns and effective connectivity (Dynamic Causal Modeling,
      DCM) while performing the Attention Network Task (ANT). Anxiety sensitivity was
      ascertained by the Anxiety Sensitivity Index (ASI). Forty patients and 48
      controls were re-scanned after a 6 weeks cognitive-behavioral treatment (CBT) or
      an equivalent waiting time, respectively. In the alerting condition, patients
      showed decreased activation in fronto-parietal pathways including the middle
      frontal gyrus and the superior parietal lobule (MFG, SPL). In addition, ASI
      scores were negatively correlated with connectivity emerging from the SPL, the
      SFB and the LC and going to the MFG in patients but not in healthy controls. CBT
      resulted in an increase in middle frontal and parietal activation along with
      increased connectivity going from the MFG to the SPL. This change in connectivity
      was positively correlated with reduction in ASI scores. There were no changes in
      controls. The present findings point to a pathological disintegration of the MFG
      in a fronto-parietal pathway in the alerting network in PD which was observed to
      be reversible by a successful CBT intervention.

PMID- 30288561
TI  - Caballeronia ginsengisoli sp. nov., isolated from ginseng cultivating soil.
AB  - A Gram-stain-negative, strictly aerobic, non-motile, ivory colored and rod-shaped
      bacterium (designated Gsoil 652T) isolated from ginseng cultivating soil, was
      characterized using a polyphasic approach to clarify its taxonomic position.
      Strain Gsoil 652T was observed to grow optimally at 30  degrees C and at pH 7.0
      on R2A agar medium. Phylogenetic analysis, based on 16S rRNA gene sequences
      similarities, indicated that Gsoil 652T belongs to the genus Caballeronia of the
      family Burkholderiaceae and was most closely related to Caballeronia choica LMG
      22940T (98.9%), Caballeronia udeis LMG 27134T (98.9%), Caballeronia sordidicola
      LMG 22029T (98.2%) and Caballeronia humi LMG 22934T (98.1%). The DNA G+C content
      was 62.1 mol% and Q-8 was the major isoprenoid quinone. The main polar lipids
      were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol,
      unidentified aminophospholipid, and unidentified phospholipid. The predominant
      fatty acids were C16:0, C17:0 cyclo and C19:0 cyclo omega8c. The DNA-DNA
      relatedness value between strain Gsoil 652T and closely related type strains of
      Caballeronia species were less than 36.0%. Moreover, strain Gsoil 652T could be
      distinguished phenotypically from the recognized species of the genus
      Caballeronia. The novel isolate, therefore, represents a novel species, for which
      the name Caballeronia ginsengisoli sp. nov. is proposed, with the type strain
      Gsoil 652T (= KACC 19441T = LMG 30326T).

PMID- 30288562
TI  - Isolation and identification of Ammodendron bifolium endophytic bacteria and the
      action mechanism of selected isolates-induced seed germination and their effects
      on host osmotic-stress tolerance.
AB  - This study aimed to identify Ammodendron bifolium endophytic bacteria, and to
      evaluate promoting mechanism of selected isolates on seed germination and their
      effects on host osmotic-stress tolerance. Forty-five strains were isolated from
      A. bifolium and were classified into 13 different genera by 16S rDNA gene
      sequence analysis. AY3, AY9 and AG18, which were identified as Staphylococcus,
      Kocuria, Bacillus sp., promoted host seed ethylene release during germination.
      Ethrel and 1-aminocyclopropane-1-carboxylic acid (ACC) imitated the effect of
      AY3, AY9 and AG18 on seed germination. The data suggest that ethylene mediates
      AY3-, AY9-, AG18-induced A. bifolium seed germination. In addition, osmotic
      stress prevented seed germination and radicle elongation. However, the inhibitory
      effect of osmotic stress on seed germination and radicle elongation were rescued
      by AY3, AY9 and AG18. The results show that AY3, AY9 and AG18 increased osmotic
      stress tolerance in A. bifolium. AY3, AY9, AG18 induced A. bifolium seed
      germination through promoting ethylene production during endophytic bacteria
      plant interaction, and increase osmotic-stress tolerance in A. bifolium. AY3, AY9
      and AG18 are potential candidates for the protection of A. bifolium.

PMID- 30288563
TI  - Oral Isotretinoin in the Treatment of Postoperative Edema in Thick-Skinned
      Rhinoplasty: A Randomized Placebo-Controlled Clinical Trial.
AB  - BACKGROUND: The thick-skinned nose is still one of the most challenging aspects
      of rhinoplasty. The possible effects of oral isotretinoin on cosmetic results of
      rhinoplasty in patients with thick nasal skin have been considered during recent
      years. METHODS: In this double-blind placebo-controlled clinical trial, 48 cases
      were divided into two groups randomly. Oral isotretinoin (0.5-mg/kg) was started
      on the 31st day after surgery and given every other day for 1 month and after
      that daily for two additional months in the first group. The second group
      received a placebo in the same form, sequence and interval as the first group.
      The cosmetic results based on patient satisfaction and ranking by an expert
      surgeon were compared between the two groups at 3 months, 6 months and 1 year
      after surgery. RESULTS: Patient satisfaction and ranking by an expert surgeon in
      the isotretinoin group at 3 months and 6 months after surgery were significantly
      better than in the placebo group (p value < 0.05); however, at 12 months after
      surgery there was no statistically significant difference between the two groups
      (p value > 0.05). CONCLUSION: Though postoperative use of oral isotretinoin in
      patients with thick nasal skin accelerates improvement in cosmetic results during
      the early months after surgery, it does not significantly affect the final
      cosmetic result 1 year after surgery. LEVEL OF EVIDENCE II: This journal requires
      that authors assign a level of evidence to each article. For a full description
      of these Evidence-Based Medicine ratings, please refer to the Table of Contents
      or the online Instructions to Authors www.springer.com/00266 .

PMID- 30288564
TI  - The Ideals of Facial Beauty Among Chinese Aesthetic Practitioners: Results from a
      Large National Survey.
AB  - : As the demand for cosmetic procedures increases, the importance of patient
      centred care in this field becomes more prominent. The aesthetic practitioners'
      ideals of beauty, in addition to their knowledge and perception of patients'
      ideals of beauty and expectations, are important during doctor-patient
      communication. These are important in strengthening practices of patient-centred
      communication and treatment. This study was conducted to investigate ideals of
      facial beauty among Chinese aesthetic practitioners. A questionnaire with simple
      sketches of facial features was given to aesthetic practitioners in Chinese
      cosmetology hospitals and clinics to assess aesthetic practitioners' ideals of
      beauty and their preferences for facial shapes, facial profile, nose and lip
      shape, jaw angle, and chin shape. A total of 596 surveys were completed. This
      survey revealed that Chinese aesthetic practitioners preferred a heart/inverted
      triangular facial shape with a reduced lower face height, a straight and small
      nose, as well as lips that are full medially and taper off laterally with well
      defined borders and Cupid's bow. An obtuse jaw angle for women and a square well
      defined jaw angle for men, and a round and pointy chin for both women and men
      were the most preferred. A majority (66.7%) of the respondents said they would
      have plastic surgery. However, if given the choice 82.9% indicated they would opt
      for non-surgical procedures. Finally, a clear majority (90.5%) believed that
      being beautiful would improve their daily life. The results were then compared to
      a similar previous study in which the same ideals of beauty were investigated
      among Chinese laypersons. This information will help the aesthetic professionals
      to understand their patient's requests and expectations better and therefore aid
      in offering and providing treatments that are in line. LEVEL OF EVIDENCE V: This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these Evidence-Based Medicine ratings, please refer to the
      Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 30288565
TI  - Complication of Ruptured Poly Implant Prothese(r) Breast Implants Combined with
      AQUAfilling(r) Gel Injection: A Case Report and Literature Review.
AB  - INTRODUCTION: We describe the first case of a patient who received AQUAfilling(r)
      gel (Biomedica, Prague, Czech Republic) after augmentation with Poly Implant
      Prothese(r) (PIP) breast implants and later developed breast deformity with
      bilateral implant rupture. CASE REPORT: A 49-year-old Korean female patient who
      received breast augmentation with PIP implants 18 years ago and subsequent
      insertion of AQUAfilling(r) gel 1 year ago visited our center with a chief
      complaint of pain and decreased implant sizes in both breasts. Breast implant and
      foreign body removal operation was performed for both breasts under general
      anesthesia. Intraoperative gross findings, pathologic findings, and tissue
      culture results were analyzed. RESULTS: Our diagnosis included rupture of the
      implants in both breasts with leakage of injected material resulting in
      inflammation of the pericapsular area and pectoralis muscle. The intraoperative
      gross findings and results of the pathologic report showed that the implants were
      exposed with massive leakage of AQUAfilling(r) gel in the pericapsular space, and
      the pectoralis major was mixed with AQUAfilling(r) gel-like liquid and tissue
      with an inflammatory reaction. CONCLUSIONS: Surgeons should be careful in
      performing AQUAfilling(r) gel injection for breast augmentation, especially when
      combined with breast implant insertion. AQUAfilling(r) gel itself is not yet
      proven safe in the long term, so more research on this topic is warranted.
      Additionally, surgeons should be aware of the comparatively high risk of implant
      rupture and foreign body reaction with PIP implants, and warn patients
      accordingly. LEVEL OF EVIDENCE V: This journal requires that authors assign a
      level of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 30288566
TI  - Comparison of leg loader and treadmill exercise for evaluating patients with
      peripheral artery disease.
AB  - The exercise ankle-brachial index (ABI) helps diagnose lower extremity peripheral
      artery disease (PAD). Patients with comorbidities may be unable to perform
      treadmill exercise, the most common stress loading test. While the active pedal
      plantar flexion (APP) test using the leg loader, simple and easy stress loading
      device, could be an alternative, there are no data comparing the leg loader and
      treadmill exercise. Therefore, we aimed to compare APP using the leg loader and
      treadmill exercise to evaluate PAD. A total of 27 patients (54 limbs) diagnosed
      with PAD with intermittent claudication and considered for angiography and/or
      endovascular treatment were recruited prospectively, and both the leg loader and
      treadmill were performed. There was a strong correlation (r = 0.925, p < 0.001)
      between the leg loader ABI and treadmill ABI; however, the decrease rate of the
      leg loader ABI was significantly less than that of treadmill ABI (14.0% [5.6,
      30.1] vs. 25.8% [6.1, 53.1], p < 0.001). The number of patients who terminated
      the exercise prematurely due to dyspnea was four during the treadmill and zero
      during the leg loader. There was a good correlation between the leg loader ABI
      and treadmill ABI. Although leg loader, a simple, safe, and easy method, could be
      an alternative to diagnose PAD, further studies are needed to evaluate the
      diagnostic value of the leg loader in patients with borderline ABI or those
      unable to perform the treadmill.

PMID- 30288567
TI  - Prevalence of early repolarization syndrome and long-term clinical outcome in
      patients with the diagnosis of idiopathic ventricular fibrillation.
AB  - Idiopathic ventricular fibrillation (IVF) is diagnosed in up to 14% of sudden
      cardiac death (SCD) survivors. Early repolarization syndrome (ERS) in patients
      with ventricular tachyarrhythmia is characterized by an elevated J-point in
      inferior and/or antero-lateral leads. Our objectives were to determine the
      prevalence of ERS in IVF patients, and to evaluate potential differences in
      clinical outcome. Out of 3,552 implantable cardioverter defibrillator (ICD)
      carriers, 758 SCD survivors were retrospectively identified from the databases of
      the Medical Universities of Vienna and Innsbruck within the last three decades.
      Early repolarization pattern (ERP) was classified either as "notching" or
      "slurring". Endpoints were defined as appropriate ICD therapies for ventricular
      tachyarrhythmia, either anti-tachycardia pacing or shock, and all-cause
      mortality. After exclusion of recognized reasons for SCD, 50 patients were
      assigned to the diagnosis of IVF (6.6%). An ERP was identified in 10 patients,
      most of them with notching (n = 8). After a mean follow-up of 11.2 +/- 6.7 years
      (539.3 patient years), appropriate ICD therapies were found in 50% of ERS and 43%
      of IVF patients without ERP (p = 0.732). In ERS patients, all ICD therapies were
      found in patients with notching pattern. Similarly, incidence of inappropriate
      ICD therapies, and all-cause mortality was comparable (30% vs. 23%, p = 0.707;
      10% vs. 5%, p = 0.496, respectively). In 758 SCD survivors, we found a low
      prevalence of IVF and ERS. Similar event rates were reported concerning all-cause
      mortality and ICD therapies for ventricular tachyarrhythmia after long-term
      follow-up in this cohort.

PMID- 30288568
TI  - Abnormal tibial alignment is a risk factor for lateral meniscus posterior root
      tears in patients with anterior cruciate ligament ruptures.
AB  - PURPOSE: The purpose of this study was to identify if abnormal tibial alignment
      was a risk factor for lateral meniscus posterior root tears (LMPRT) in patients
      with acute anterior cruciate ligament (ACL) ruptures. METHODS: The medical charts
      of 200 patients treated for ACL ruptures between 2013 and 2016 were
      retrospectively reviewed and evaluated. MRI images and reports were assessed for
      concurrent meniscal tears. Radiographs were reviewed for tibia vara and tibial
      slope angles and MRI reports identifying lateral root tears were compared to
      intraoperative reports to determine accuracy. Multiple logistic regression models
      were constructed to identify potential risk factors for LMPRTs. RESULTS: Of the
      200 patients reviewed, a total of 97 individuals with concurrent meniscal
      injuries were identified. In patients sustaining a concurrent meniscal injury,
      there was a 4% incidence of medial meniscus posterior root tears and a 10.3%
      incidence of LMPRTs. Patients sustaining an ACL injury with an LMPRT were found
      to have greater tibia vara angles (4.2 +/- 1.0 vs. 2.9 +/- 1.7; p = 0.024),
      increased tibial slopes (12.6 +/- 1.5 vs. 10.7 +/- 2.9; p = 0.034), and higher
      BMIs (27.3 +/- 2.9 vs. 25.3 +/- 5.9; p = 0.034) when compared to patients without
      meniscus tears. There was low agreement between MRI and arthroscopic findings
      (kappa rate = 0.54). Multiple logistic regression analysis demonstrated that a
      tibia vara angle > 3 was associated with a 5.2-fold increase (95% CI 0.99-27.01;
      p = 0.050), and a tibial slope > 12 with a 5.4-fold increase (95% CI 1.03-28.19;
      p = 0.046) in LMPRTs. CONCLUSIONS: Patients with greater tibia varus angles,
      increased tibial slopes, and higher BMIs were found to have an increased risk of
      LMPRTs when sustaining an ACL rupture. There was a low rate of agreement between
      MRI and arthroscopy in identifying LMPRTs. In patients with ACL ruptures who have
      abnormal tibial alignment or increased BMI, physicians should be watchful for
      lateral meniscus posterior root tears. LEVEL OF EVIDENCE: 3.

PMID- 30288569
TI  - A load-measuring device can achieve fine-tuning of mediolateral load at knee
      arthroplasty but may lead to a more lax knee state.
AB  - PURPOSE: A balanced knee arthroplasty should optimise survivorship and
      performance. Equilibration of medial and lateral femorotibial load requires
      guided judicious pericapsular ligament release. The null hypothesis was that
      there would be no difference between use of a tensiometer device and a remote
      load sensor final load transfer across the joint through functional arc of
      motion. METHODS: A cadaveric study, using eight knees, was performed to define
      the impact of an established gap distraction device against load sensor-aimed
      soft tissue release in a TKA setting. Using validated measures of laxity in six
      degrees of freedom and true real-time load sensing four states were examined:
      native knee, TKA using spacer blocks (TKA), TKA with soft tissue release aided by
      a monogram tensiometer (TKA-T) and finally where load across the tibiofemoral
      articulation remains unbalanced final soft tissue release using a sensor device
      (TKA-OS). RESULTS: The laxity pattern was equivalent for TKA-T and TKA-OS.
      However, in only four of these seven knees despite the tensiometer confirming
      equivalence of rectangular flexion-extension gap dimensions and centralisation of
      collateral ligament distraction, there remained a > 15lb medial to lateral load
      difference for at least one point of the flexion arc. This was corrected by
      further final soft tissue release guided by the OS sensor device in the final
      three knees. CONCLUSION: Tensiometer-guided soft tissue release at two points of
      flexion failed to achieve balance for three out of seven knee arthroplasty
      procedures. Sensor technology guided final soft tissue balancing to equilibrate
      load across the joint through full arc of motion. This work argues for the role
      of continuous sensor readings to guide the soft tissue balancing during total
      knee arthroplasty.

PMID- 30288570
TI  - Pre-existing patellofemoral disease does not affect 10-year survivorship in fixed
      bearing unicompartmental knee arthroplasty.
AB  - PURPOSE: The purpose of this study was to assess 10-year functional outcome and
      survivorship analysis of patients with significant radiographic evidence of
      patellofemoral joint arthritis treated with fixed bearing unicompartmental knee
      arthroplasty. METHODS: Two hundred and sixteen patients (263 knees) that
      underwent UKA from 2003 to 2005 for a mean of 10.5 +/- 2.1 years were
      prospectively followed up. Preoperative radiological assessment of the
      patellofemoral joint state was assessed according to the Ahlback classification
      by an independent assessor and radiographically significant patellofemoral
      disease was defined as grade 2 or more. Patients with significant bone-on-bone
      contact in the patellofemoral joint were excluded. RESULTS: Of the 263 knees, 222
      (84.4%) had normal patellofemoral joint state and 41 (15.6%) radiologically
      significant patellofemoral disease. At 10 years' follow-up, the normal and
      patellofemoral groups had similar OKS (20 +/- 7 vs 20 +/- 8, n.s.) and KSS scores
      (79 +/- 20 vs 81 +/- 20, n.s.), respectively. There were 12 revision surgeries in
      the normal group and the most common indication for revision was progression of
      contralateral compartment osteoarthritis (6 of 12 cases). There was only one
      revision in the patellofemoral group and it was due to progression of
      contralateral compartment osteoarthritis (n.s.). When all secondary surgeries to
      the operated knee were considered as failures, the 10-year survival rate was
      95.1% (CI 95%: 92.2-97.7%). CONCLUSION: The presence of significant preoperative
      radiological patellofemoral disease does not affect long-term implant survival
      and patients have excellent functional outcomes 10 years postoperatively. These
      patients should not be contraindicated from undergoing unicompartmental knee
      arthroplasty. LEVEL OF EVIDENCE: III.

PMID- 30288572
TI  - Serum kidney injury molecule 1 and beta2-microglobulin perform as well as larger
      biomarker panels for prediction of rapid decline in renal function in type 2
      diabetes.
AB  - AIMS/HYPOTHESIS: As part of the Surrogate Markers for Micro- and Macrovascular
      Hard Endpoints for Innovative Diabetes Tools (SUMMIT) programme we previously
      reported that large panels of biomarkers derived from three analytical platforms
      maximised prediction of progression of renal decline in type 2 diabetes. Here, we
      hypothesised that smaller (n <= 5), platform-specific combinations of biomarkers
      selected from these larger panels might achieve similar prediction performance
      when tested in three additional type 2 diabetes cohorts. METHODS: We used 657
      serum samples, held under differing storage conditions, from the Scania Diabetes
      Registry (SDR) and Genetics of Diabetes Audit and Research Tayside (GoDARTS), and
      a further 183 nested case-control sample set from the Collaborative Atorvastatin
      in Diabetes Study (CARDS). We analysed 42 biomarkers measured on the SDR and
      GoDARTS samples by a variety of methods including standard ELISA, multiplexed
      ELISA (Luminex) and mass spectrometry. The subset of 21 Luminex biomarkers was
      also measured on the CARDS samples. We used the event definition of loss of >20%
      of baseline eGFR during follow-up from a baseline eGFR of 30-75 ml min-1 [1.73 m]
      2. A total of 403 individuals experienced an event during a median follow-up of 7
      years. We used discrete-time logistic regression models with tenfold cross
      validation to assess association of biomarker panels with loss of kidney
      function. RESULTS: Twelve biomarkers showed significant association with eGFR
      decline adjusted for covariates in one or more of the sample sets when evaluated
      singly. Kidney injury molecule 1 (KIM-1) and beta2-microglobulin (B2M) showed the
      most consistent effects, with standardised odds ratios for progression of at
      least 1.4 (p < 0.0003) in all cohorts. A combination of B2M and KIM-1 added to
      clinical covariates, including baseline eGFR and albuminuria, modestly improved
      prediction, increasing the area under the curve in the SDR, Go-DARTS and CARDS by
      0.079, 0.073 and 0.239, respectively. Neither the inclusion of additional Luminex
      biomarkers on top of B2M and KIM-1 nor a sparse mass spectrometry panel, nor the
      larger multiplatform panels previously identified, consistently improved
      prediction further across all validation sets. CONCLUSIONS/INTERPRETATION: Serum
      KIM-1 and B2M independently improve prediction of renal decline from an eGFR of
      30-75 ml min-1 [1.73 m]-2 in type 2 diabetes beyond clinical factors and prior
      eGFR and are robust to varying sample storage conditions. Larger panels of
      biomarkers did not improve prediction beyond these two biomarkers.

PMID- 30288575
TI  - ?

PMID- 30288574
TI  - [Boys' consultation-support for boys with problems during puberty].

PMID- 30288573
TI  - [Urological challenges in refugees and migrants].

PMID- 30288576
TI  - ?

PMID- 30288577
TI  - ?

PMID- 30288578
TI  - ?

PMID- 30288579
TI  - ?

PMID- 30288580
TI  - ?

PMID- 30288581
TI  - A gene graveyard in the genome of the fungus Podospora comata.
AB  - Mechanisms involved in fine adaptation of fungi to their environment include
      differential gene regulation associated with single nucleotide polymorphisms and
      indels (including transposons), horizontal gene transfer, gene copy
      amplification, as well as pseudogenization and gene loss. The two Podospora
      genome sequences examined here emphasize the role of pseudogenization and gene
      loss, which have rarely been documented in fungi. Podospora comata is a species
      closely related to Podospora anserina, a fungus used as model in several
      laboratories. Comparison of the genome of P. comata with that of P. anserina,
      whose genome is available for over 10 years, should yield interesting data
      related to the modalities of genome evolution between these two closely related
      fungal species that thrive in the same types of biotopes, i.e., herbivore dung.
      Here, we present the genome sequence of the mat + isolate of the P. comata
      reference strain T. Comparison with the genome of the mat + isolate of P.
      anserina strain S confirms that P. anserina and P. comata are likely two
      different species that rarely interbreed in nature. Despite having a 94-99% of
      nucleotide identity in the syntenic regions of their genomes, the two species
      differ by nearly 10% of their gene contents. Comparison of the species-specific
      gene sets uncovered genes that could be responsible for the known physiological
      differences between the two species. Finally, we identified 428 and 811
      pseudogenes (3.8 and 7.2% of the genes) in P. anserina and P. comata,
      respectively. Presence of high numbers of pseudogenes supports the notion that
      difference in gene contents is due to gene loss rather than horizontal gene
      transfers. We propose that the high frequency of pseudogenization leading to gene
      loss in P. anserina and P. comata accompanies specialization of these two fungi.
      Gene loss may be more prevalent during the evolution of other fungi than usually
      thought.

PMID- 30288582
TI  - Shear wave elastography prior to transjugular intrahepatic portosystemic shunt
      may predict the decrease in hepatic vein pressure gradient.
AB  - BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure
      used to treat portal hypertension complications. Our aim was to evaluate liver
      and spleen stiffness measurement (LSM and SSM, respectively) changes using
      acoustic radiation force impulse imaging (ARFI) in comparison to Child-Pugh
      scores for predicting hepatic venous pressure gradient (HVPG) decreases after
      TIPS implantation. METHODS: This prospective study included 31 consecutive
      clinically significant portal hypertension patients with TIPS indication. All
      patients received LSM and SSM before TIPS, at baseline, 2 days (follow-up 1) and
      6 weeks (follow-up 2) post-implantation. HVPG was performed during the TIPS
      procedure. RESULTS: The mean decrease in HVPG after TIPS was 63%. LSM and SSM
      decreased significantly between baseline and follow-up 2 (p < 0.001 and p <
      0.001, respectively). At baseline, follow-up 1 and follow-up 2, significant
      correlations were detected between mean SSM and mean HVPG (p = 0.026; p = 0.018;
      p = 0.002, respectively). HVPG decreased to <= 10 mmHg in 61% of patients for
      which LSM, SSM, and Child-Pugh score were predictors (p = 0.033, p = 0.002 and p
      = 0.030, respectively). The area under the curve (AUC) for LSM, SSM, and Child
      Pugh was 0.88, 0.90, and 0.84, respectively, with close sensitivity and
      specificity. SSM had the highest diagnostic accuracy for predicting an HVPG
      decrease to <= 10 mmHg in comparison to LSM and Child-Pugh score. CONCLUSION:
      Spleen stiffness is superior to liver stiffness and Child-Pugh score as a non
      invasive surveillance tool for evaluating patients with clinically significant
      portal hypertension (HVPG >= 10 mmHg) prior to TIPS.

PMID- 30288571
TI  - Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the
      American Diabetes Association (ADA) and the European Association for the Study of
      Diabetes (EASD).
AB  - The American Diabetes Association and the European Association for the Study of
      Diabetes convened a panel to update the prior position statements, published in
      2012 and 2015, on the management of type 2 diabetes in adults. A systematic
      evaluation of the literature since 2014 informed new recommendations. These
      include additional focus on lifestyle management and diabetes self-management
      education and support. For those with obesity, efforts targeting weight loss,
      including lifestyle, medication and surgical interventions, are recommended. With
      regards to medication management, for patients with clinical cardiovascular
      disease, a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like
      peptide-1 (GLP-1) receptor agonist with proven cardiovascular benefit is
      recommended. For patients with chronic kidney disease or clinical heart failure
      and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven
      benefit is recommended. GLP-1 receptor agonists are generally recommended as the
      first injectable medication.

PMID- 30288584
TI  - The little rose sign.

PMID- 30288583
TI  - The honeycomb pattern of pancreatic serous cystadenoma.

PMID- 30288585
TI  - Overview of systemic treatment in recurrent and advanced cervical cancer: a
      primer for radiologists.
AB  - Imaging has a central role in surveillance of cervical cancer, guiding decision
      on when to initiate treatment for recurrent disease and to guide management in
      advanced cervical cancer. Due to the increased availability of pelvic radiation
      therapy, the rate of atypical presentation of recurrent disease has increased.
      Simultaneously, the array of systemic therapies now available for advanced
      cervical cancer has considerably expanded in the last few years, with therapies
      now available in mid and low-income countries. While pelvic recurrences are
      amenable of loco-regional treatment, recurrent disease may present with
      metastases to the thoracoabdominal organs, lymph nodes, bones, skin and brain,
      for which systemic treatment represent the standard of care. Besides combined
      chemotherapy regimens, alternative chemotherapies, biosimilars and immune
      checkpoint inhibitors are now available, each associated with a definite pattern
      of response and toxicity. In this review, after describing the typical and
      atypical presentations of recurrent and advanced cervical carcinoma on cross
      sectional imaging, we will discuss systemic treatment for recurrent or advanced
      disease and their associated radiographic sequelae, in light of the newly
      available therapies.

PMID- 30288586
TI  - Effect of thyme essential oil against Bacillus cereus planktonic growth and
      biofilm formation.
AB  - The objective of this study was to determine the effect of thyme essential oil
      (TEO) on the planktonic growth and biofilm formation of Bacillus cereus (B.
      cereus). GC-MS analysis of TEO allowed the detection of 13 compounds, and the
      major constituents were p-cymene (29.7%), thymol (23.73%), gamma-terpinene
      (16.21%), and 1,8-cineole (9.74%). TEO exhibited a minimum inhibitory
      concentration (MIC) value against planktonic B. cereus of 0.25 mg/mL. The potent
      effect of TEO to inhibit the growth of planktonic B. cereus was due to cell
      membrane damage, as evidenced by reduced cell viability, protein changes,
      decreased intracellular ATP concentration, increased extracellular ATP
      concentration and cell membrane depolarization, and cellular morphological
      changes. In addition, TEO exerted a significant inhibitory effect on B. cereus
      biofilm formation, as confirmed by environmental scanning electron microscopic
      images. These findings suggested that TEO has the potential to be developed as a
      natural food additive to control foodborne contamination associated with B.
      cereus and its biofilm.

PMID- 30288587
TI  - A new strategy for fed-batch process control of HEK293 cell cultures based on
      alkali buffer addition monitoring: comparison with O.U.R. dynamic method.
AB  - The increasing demand for biopharmaceuticals produced in mammalian cells has
      driven the industry to enhance productivity of bioprocesses through different
      strategies. This is why fed-batch and perfusion cultures are considered more
      attractive choices than batch processes. In this context, the availability of
      reliable online measuring systems for cell density and metabolic activity
      estimation will help the application of these processes. The present work focuses
      on the comparison of two different monitoring tools for indirect estimation of
      biomass concentration in a HEK293 cell cultures producing IFN-gamma: on one side,
      the oxygen uptake rate (O.U.R.) determination, by means of application of the
      dynamic method measurement which is already a widely used tool and, on the other
      side, a new robust online monitoring tool based on the alkali buffer addition
      used to maintain the pH set point. Both strategies allow a proper monitoring of
      cell growth and metabolic activity, with precise identification of the balanced
      cell growth and the most important action in the process, as is the media
      feeding. The application of these monitoring systems in fed-batch processes
      allows extending the growth of HEK293 cells, which in turn results in higher
      final cell concentrations compared with Batch strategy (7 . 106 cells mL-1),
      achieving 14 . 106 cells mL-1 for the fed-batch based on O.U.R. and 19 . 106
      cells mL-1 for the fed-batch based on the alkali addition. Product titter is also
      increased in respect of the batch strategy (3.70 mg L-1), resulting in 8.27 mg L
      1 when fed-batch was based on O.U.R. and 11.49 mg L-1 when it was based on the
      alkali buffer strategy. Results prove that fed-batch strategy based on the alkali
      buffer addition is a robust online monitoring method that has shown its great
      potential to optimize the feeding strategy in HEK293 fed-batch cultures.

PMID- 30288588
TI  - Radiofrequency Wire Recanalization of Chronically Occluded Venous Stents: A
      Retrospective, Single-Center Experience in 15 Patients.
AB  - INTRODUCTION: Chronically occluded venous stents may be difficult to salvage,
      necessitating multiple approaches and adjunctive techniques. Radiofrequency wires
      have been used to cross chronic obstructions in a variety of settings. Herein,
      radiofrequency wire recanalization (RFWR) of chronically occluded venous stents
      is presented. MATERIALS AND METHODS: Fifteen patients (8 males; 7 females) aged
      23-74 years (median 42 years) underwent prior venous stenting in the setting of
      venous occlusions. Seven had an underlying coagulopathy, three had May-Thurner
      syndrome, three had provoked deep venous thrombosis, one had a dialysis fistula,
      and one had pacer leads in situ. All indwelling venous stents were chronically
      occluded and symptomatic. Out of 15 patients, 13 (87%) had iliocaval venous
      stents, while two (13%) had superior vena cava and/or upper extremity venous
      stents. After failing conventional and blunt recanalization techniques, RFWR was
      performed to traverse the chronic occlusions. Technical success and complications
      were recorded. RESULTS: Fifteen patients underwent 19 procedures. Twelve patients
      underwent one procedure, two patients had two procedures, and one patient had
      three procedures. RFWR alone was used in 12/19 (63%) procedures, while 7/19 (37%)
      required adjunctive sharp recanalization techniques. Technical success or
      crossing of the occlusion with flow restoration through the occluded segments was
      achieved in 17/19 (89%). One major and one minor complication occurred.
      CONCLUSION: Radiofrequency wire recanalization is an effective adjunct to revise
      chronically occluded venous stents, potentially increasing procedural success in
      challenging cases.

PMID- 30288589
TI  - Ablation Volume Measurement After Percutaneous Cryoablation Using a Two-cryo
      probe Technique for Small Hepatocellular Carcinomas.
AB  - PURPOSE: To calculate the ablation volume of percutaneous cryoablation (PCA) with
      a two-cryo-probe technique for small hepatocellular carcinomas (HCCs) and to
      assess risk factors for local tumor recurrence (LTR). MATERIALS AND METHODS:
      Between January 2013 and June 2017, 96 patients (mean age, 60.7 years; range, 37
      83 years) with 106 small HCCs were retrospectively analyzed. The ablation volume,
      technical success, LTR rates, and complications were evaluated. Ablation volume
      was measured after the first freezing and immediately after completing PCA twice
      via computed tomography imaging. Prognostic factors associated with LTR were
      analyzed. RESULTS: Technical success was achieved in all patients. The mean final
      ablation volume was 19.1 +/- 4.8 cm3, which was significantly higher than the
      first freezing ablation volume (14.7 +/- 4.3 cm3, p < 0.001). During the median
      follow-up period of 16.7 months (range, 5-52 months), LTR-free survival rates
      based on Kaplan-Meier analyses at 6 months, 1 year, and 2 years were 87.7%,
      84.0%, and 80.2%, respectively. Only one major complication of post-procedural
      arterial bleeding occurred. A final ablation volume/tumor volume < 10 was a
      significant risk factor for LTR (p = 0.044). CONCLUSIONS: A ratio of final
      ablation volume to tumor volume < 10 was a significant prognostic factor for LTR.
      Therefore, the measurement and prediction of the final ablation volume are
      important to reduce LTR.

PMID- 30288590
TI  - Long-Term Evaluation of Percutaneous Groin Access for EVAR.
AB  - BACKGROUND: Percutaneous endovascular aneurysm repair (PEVAR) has been shown to
      have high success rates, shorter operating times and length of stay compared to
      open access. However, there exists a lack of long-term follow-up data on these
      patients, and questions remain regarding longer-term outcomes. This study aims to
      assess the long-term complications and evolution of accessed vessels post-PEVAR.
      METHODS: Sixty-one cases of bilateral PEVAR (122 groins) with > 36 months follow
      up were analysed. Vessel diameter, calcification, dissection, lymphocele,
      pseudoaneurysm and thrombus formation were reviewed at 30th day and at the most
      recent follow-up CT. Notes were reviewed for groin infections, haematomas and
      nerve injury. Complications were considered 'major' if they required intervention
      or treatment. RESULTS: Mean follow-up time from procedure to most recent scan was
      49.9 months. There were no major short- or long-term complications. The early
      complication rate was 9.8%, with six pseudoaneurysms, four dissections, one
      thrombus, one nerve injury and no lymphoceles, haematomas or groin infections.
      The long-term complication rate was 0.8%, with only one pseudoaneurysm. The
      remainder of early complications resolved naturally without intervention.
      Accessed vessel showed significantly (P <= 0.05) increased diameter and
      calcification between 30th day and last follow-up scan. CONCLUSION: This study
      provides the largest clinical cohort and the longest mean follow-up time reported
      in the literature and demonstrates the long-term safety of PEVAR. PEVAR has a
      very low long-term complication rate, without any major complications in our
      cohort. The accessed common femoral arteries do not show stenosis or thrombosis.
      Minor short-term complications appear to gradually resolve without intervention.
      Larger multi-centre studies are recommended.

PMID- 30288591
TI  - Uterine Artery Embolization in Women with Symptomatic Cervical Leiomyomata:
      Efficacy and Safety.
AB  - PURPOSE: To perform an evaluation on safety and efficacy of uterine artery
      embolization (UAE) in the patients with symptomatic cervical leiomyomata.
      METHODS: Patients with symptomatic cervical leiomyomata who underwent UAE in one
      specialized hospital were retrospectively analyzed, both clinically and with MR
      imaging. The 3-month outcomes were assessed with MR imaging and a validated
      questionnaire. Long-term follow-up was assessed by direct contact or file review.
      To determine the efficacy of UAE for cervical leiomyomata, the primary objective
      was to assess the clinical outcome with the UFS-QOL questionnaire, containing the
      health-related quality of life (HRQOL) and symptom severity score (SSS). To
      assess safety, the secondary objective included leiomyomata volume reduction, the
      infarction/complication rate and secondary interventions were needed. RESULTS:
      Between 2006 and 2017, eight of 1180 patients underwent UAE and were eligible for
      inclusion. All embolizations were technically successful (n = 8). At 3 months,
      all patients showed cervical leiomyomata volume reduction with a median reduction
      of 41.5% (38.8 cm3) compared to baseline (p = 0.012). No complications occurred.
      At a median follow-up of 3 months (range 1-7, n = 7), the HRQOL and SSS improved
      with a median difference of 13 points (range - 5 to 60, p = 0.063) and - 13
      points (range - 79 to 3, p = 0.046), respectively. Long-term follow-up showed two
      secondary interventions (median of 43.5 months). Six patients reported no symptom
      recurrence. CONCLUSION: UAE in women with symptomatic cervical leiomyomata is
      effective and safe with significant improvement in symptoms and quality of life.
      UAE is a valuable option for women seeking a non-surgical solution.

PMID- 30288592
TI  - Factors Associated with Secondary Functional Patency After Percutaneous
      Transluminal Angioplasty of the Early Failing or Immature Hemodialysis
      Arteriovenous Fistula.
AB  - PURPOSE: To evaluate the efficacy of percutaneous transluminal angioplasty for
      early failing hemodialysis arteriovenous fistulas (AVFs) and predictors of
      secondary functional patency (FP). METHODS: A review of our endovascular registry
      database showed that 61 patients with early failure after a surgically created
      AVF underwent endovascular intervention between 2011 and 2016. Median time from
      AVF creation to first intervention was 5.6 weeks. Median duration of follow-up
      was 14 months. Items related to the technical success rate and primary and
      secondary FP, and factors associated with secondary FP were analyzed. RESULTS:
      Technical success was achieved in 55 (90%) of 61 patients. The primary and
      secondary FP rates were 42% and 65% at 12 months, respectively. Multivariate
      analysis showed that lesion length (HR; 1.15, P = 0.001) and lesions including
      juxta-AVF (the portion of fistula vein within 2 cm of the arteriovenous
      anastomosis, HR; 6.23, P = 0.008) were factors associated with reduced secondary
      FP. ROC curve analysis indicated lesion length with cutoff value >= 9 cm as a
      risk factor for reduced secondary FP. Secondary FP at 12 months for patients with
      no risk factors, with 1, and with 2 was 86%, 65%, and 0%, respectively. There was
      a significant difference in secondary FP rates among these groups (P = 0.001).
      CONCLUSIONS: A lesion length and juxta-AVF lesion are the risk factors for
      reduced secondary FP. The secondary FP rate at 12 months is acceptable in
      patients without risk factors.

PMID- 30288593
TI  - Real-Time US-18FDG-PET/CT Image Fusion for Guidance of Thermal Ablation of 18FDG
      PET-Positive Liver Metastases: The Added Value of Contrast Enhancement.
AB  - PURPOSE: To assess the feasibility of US-18FDG-PET/CT fusion-guided microwave
      ablation of liver metastases either poorly visible or totally undetectable with
      US, CEUS and CT, but visualized by PET imaging. MATERIALS AND METHODS: Twenty
      three patients with 58 liver metastases underwent microwave ablation guided by
      image fusion system that combines US with 18FDG-PET/CT images. In 28/58 tumors,
      18FDG-PET/CT with contrast medium (PET/CECT) was used. The registration technical
      feasibility, registration time, rates of correct targeting, technical success at
      24 h, final result at 1 year and complications were analyzed and compared between
      the PET/CT and PET/CECT groups. RESULTS: Registration was successfully performed
      in all cases with a mean time of 7.8 + 1.7 min (mean + standard deviation), (4.6
      + 1.5 min for PET/CECT group versus 10.9 + 1.8 min for PET/CT group, P < 0.01).
      In total, 46/58 (79.3%) tumors were correctly targeted, while 3/28 (10.7%) and
      9/30 (30%) were incorrectly targeted in PET/CT and PET/CECT group, respectively
      (P < 0.05). Complete ablation was obtained at 24 h in 70.0% of cases (n = 40
      tumors), 23/28 (82.1%) in the PET/CECT group and 17/30 (56.7%) in the PET/CT
      group (P < 0.037). Fourteen tumors underwent local retreatment (11 ablations, 2
      with resection and 1 with stereotactic body radiation therapy), while 4 tumors
      could not be retreated because of distant disease progression and underwent
      systemic therapy. Finally, 54/58 (93.1%) tumors were completely treated at 1
      year. One major complication occurred, a gastrointestinal hemorrhage which
      required surgical repair. CONCLUSIONS: Percutaneous ablation of 18FDG-PET
      positive liver metastases using fusion imaging of real-time US and pre-acquired
      18FDG-PET/CT images is feasible, safe and effective. Contrast-enhanced PET/CT
      improves overall ablation accuracy and shortens procedural duration time.

PMID- 30288596
TI  - Diagnosis and management of nocturia in current clinical practice: who are
      nocturia patients, and how do we treat them?
AB  - OBJECTIVE: To characterize the current evaluation, and efficacy of treatments in
      patients with the primary complaint of nocturia. METHODS: A retrospective chart
      review was performed of new patient encounters seen in a tertiary urology
      practice from May 2010 to September 2016 with the primary diagnosis of nocturia
      (ICD-9 788.43 and ICD-10 R35.1). RESULTS: 595 patients were identified. 403 met
      inclusion criteria. The median patient reported that nocturia episodes were 4 (1
      20). 192 patients (48%) reported previous treatment for nocturia. After the index
      visit, a bladder diary (BD) was utilized in 50% of patients, with a 62% (n = 124)
      completion rate at follow-up visit. On BD analysis, the most common etiologies of
      nocturia were nocturnal polyuria 76% (n = 90) and overactive bladder in 21% (n =
      26). Patient reported improvement with therapy after BD completion was 46% (n =
      34), similar to patients without voiding diaries (43% improvement, n = 153).
      Anticholinergics and alpha blockers were the most commonly recommended drug, but
      no specific medication was associated with nocturia improvement. Oral
      desmopressin was used in 5% of patients. CONCLUSION: Nocturia is a common
      condition and very commonly patients have sought treatment prior to presentation.
      Bladder diaries were recommended to half of the patients. Patient reported that
      improvement did not seem to correlate with completion of a bladder diary. Though
      most patients had NP the use of desmopressin was very low. Current treatments
      used in managing nocturia may lack efficacy.

PMID- 30288595
TI  - Effect of temperature on the locomotor performance of species in a lizard
      assemblage in the Puna region of Argentina.
AB  - Locomotion is relevant to the ecology of reptiles because of its presumed
      influence on an organism's Darwinian fitness. Moreover, in ectothermic species,
      physiological performance capacity is affected by body temperature. We analyzed
      two components of locomotor performance in three species of lizards, Phymaturus
      extrilidus, Liolaemus parvus, and Liolaemus ruibali, in the Puna environment of
      Argentina. First, we estimated the thermal sensitivity of locomotion by measuring
      sprint speed at four different body temperatures. We included two measures of
      sprint speed: initial velocity and long sprint for sustained runs. Based on these
      data, we calculated the optimal temperature for performance and the optimal
      performance breadth. We also estimated endurance capacity at a single
      temperature. Maximum sprint speed for L. parvus was greater than L. ruibali and
      P. extrilidus in both initial velocity and long sprint. In contrast, L. parvus
      exhibited lower levels of endurance than L. ruibali and P. extrilidus. However,
      endurance in L. ruibali exceeded that of P. extrilidus. The species differed in
      the optimal temperature for the initial velocity with the lowest for L. ruibali
      (31.8  degrees C) followed by P. extrilidus (33.25  degrees C) and then L. parvus
      (36.25  degrees C). The optimal temperature for long sprint varied between 32 and
      36  degrees C for all species. We found that all species attained maximum
      performance at body temperatures commonly experienced during daily activity,
      which was higher than the thermal quality of the environment. We found evidence
      for thermal sensitivity in locomotor performance in these species. However, we
      also show that the broad thermal breadth of performance suggests that the lizards
      are capable of sustaining near optimal levels of locomotor performance at ambient
      temperatures that would appear to be suboptimal. Thus, this lizard assemblage is
      capable of coping with the highly variable climatic conditions in the Puna region
      of Argentina.

PMID- 30288594
TI  - The neuropharmacology of sleep paralysis hallucinations: serotonin 2A activation
      and a novel therapeutic drug.
AB  - Sleep paralysis is a state of involuntary immobility occurring at sleep onset or
      offset, often accompanied by uncanny "ghost-like" hallucinations and extreme fear
      reactions. I provide here a neuropharmacological account for these hallucinatory
      experiences by evoking the role of the serotonin 2A receptor (5-HT2AR). Research
      has shown that 5-HT2AR activation can induce visual hallucinations, "mystical"
      subjective states, and out-of-body experiences (OBEs), and modulate fear
      circuits. Hallucinatory experiences triggered by serotonin-serotonergic
      ("pseudo") hallucinations, induced by hallucinogenic drugs-tend to be "dream
      like" with the experiencer having insight ("meta-awareness") that he is
      hallucinating, unlike dopaminergic ("psychotic" and "life-like") hallucinations
      where such insight is lost. Indeed, hallucinatory experiences during sleep
      paralysis have the classic features of serotonergic hallucinations, and are
      strikingly similar to perceptual and subjective states induced by hallucinogenic
      drugs (e.g., lysergic acid diethylamide [LSD] and psilocybin), i.e., they entail
      visual hallucinations, mystical experiences, OBEs, and extreme fear reactions. I
      propose a possible mechanism whereby serotonin could be functionally implicated
      in generating sleep paralysis hallucinations and fear reactions through 5-HT2AR
      activity. Moreover, I speculate on the role of 5-HT2C receptors vis-a-vis anxiety
      and panic during sleep paralysis, and the orbitofrontal cortex-rich with 5-HT2A
      receptors-in influencing visual pathways during sleep paralysis, and, in effect,
      hallucinations. Finally, I propose, for the first time, a drug to target sleep
      paralysis hallucinations and fear reactions, namely the selective 5-HT2AR inverse
      agonist, pimavanserin. This account implicates gene HTR2A on chromosome 13q as
      the underlying cause of sleep paralysis hallucinations and could be explored
      using positron emission tomography.

PMID- 30288597
TI  - Fiducial markers: can the urologist do better?
AB  - INTRODUCTION: Radiotherapy to the bladder has a risk of toxicity to pelvic
      structures, which can be reduced by using fiducial markers for targeting.
      Injectable contrast offers an alternative marker to gold seeds, which may fall
      out or exacerbate scarring. Combining contrast agents with tissue glue can
      minimize dispersion through tissue, enhancing its utility. We evaluated
      combinations of contrast agents and tissue glue using porcine bladder, for
      feasibility and utility as fiducial markers to aid image-guided radiotherapy.
      METHODS: Different contrast agents (Lipiodol ultra or Urografin) were combined
      with different tissue glues (Histoacryl, Tisseal or Glubran2). The mixtures were
      endoscopically injected into porcine bladder submucosa to identify the area of
      interest with multiple fiducial markers. The porcine bladders were imaged within
      a phantom porcine pelvis using standard radiation therapy imaging modalities. The
      feasibility as an injectable fiducial marker and visibility of each fiducial
      marker on imaging were scored as binary outcomes by two proceduralists and two
      radiation therapists, respectively. RESULTS: Lipiodol-glue combinations were
      successfully administered as multiple fiducials that were evident on CT and CBCT.
      Lipiodol with Histoacryl or Glubran2 was visible on kV imaging. The Lipiodol
      Glubran2 combination was deemed subjectively easiest to use at delivery, and a
      better fiducial on KV imaging. CONCLUSION: This study demonstrates the
      feasibility of mixing contrast medium Lipiodol with Histoacryl or Glubran2 tissue
      glue, which, injected endoscopically, provides discrete and visible fiducial
      markers to aid image-guided radiotherapy. Although promising, further study is
      required to assess the durability of these markers through a course of
      radiotherapy.

PMID- 30288598
TI  - Aquablation of the prostate: single-center results of a non-selected, consecutive
      patient cohort.
AB  - PURPOSE: Aquablation of the prostate using the AquaBeamTM system promises
      equivalent functional outcomes, reduced learning curve, and improved sexual
      function compared to transurethral prostate resection as shown in prospective
      randomized trials. This prospective cohort study aims to evaluate if published
      results can be transferred into the clinical routine in a non-selected patient
      collective. METHODS: This study includes all patients treated between September
      2017 and June 2018 with Aquablation of the prostate. Patients have been evaluated
      prospectively for the perioperative course and early follow-up. Besides voiding
      parameter and symptom score, TRUS-volume change, ejaculatory function, and
      adverse events have been recorded. RESULTS: 118 consecutive patients have been
      treated in the given time. Aquablation could be carried out successfully in all
      patients. IPSS, QoL, Qmax, and PVR improved significantly after the procedure and
      continued to improve during 3-month follow-up. Mean OR time was 20 min, TRUS
      volume decreased by 65%, and 73% of the patients retained antegrade ejaculation.
      Thirteen adverse events (> Clavien-Dindo I) occurred in 10 patients. CONCLUSION:
      The surgical ablation of the prostate using Aquablation achieved significant and
      immediate improvement of functional voiding parameters Qmax and PVR as well as
      symptomatic improvement of IPSS and QoL. Aquablation seems to be safe and
      effective with a low perioperative complication profile even in a non-selected
      group of patients.

PMID- 30288599
TI  - Reference Intervals and Percentile Curves of Echocardiographic Left Ventricular
      Mass, Relative Wall Thickness and Ejection Fraction in Healthy Children and
      Adolescents.
AB  - Despite the clinical utility of echocardiography to measure cardiac target organ
      injury (TOI) there are scarcities of data about the reference intervals (RIs) and
      percentiles of left ventricular (LV) mass (LVM) and derived indexes (LVMI and
      LVMI2.7), relative wall thickness (LVRWT) and ejection fraction (LVEF) from
      population-based studies in children and adolescents. The aim of this study was
      to generate reference intervals RIs of LVM and derived indexes (LVMI and
      LVMI2.7), LVRWT, and LVEF obtained in healthy children, adolescents, and young
      adults from a South-American population. Echocardiographic studies were obtained
      in 1096 healthy subjects (5-24 years). Age and sex-specific RIs of LVM, LVMI,
      LVMI2.7, LVRWT, and LVEF were generated using parametric regression based on
      fractional polynomials. After covariate analysis (i.e., adjusting by age, body
      surface area) specific sex-specific RIs were evidenced as necessaries. Age and
      sex-specific 1st, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th, and
      99th percentile and curves were reported and compared with previously reported
      RIs. RIs showed high concordance and complementarity with what was previously
      reported for the population of North-American children (0-18 years old). In
      conclusion, in children and adolescents the interpretation of the LVM, LVMIs,
      LVRWT, and LVEF RIs requires sex-related RIs. This study provides the largest
      Argentinean database concerning RIs and percentile curves of LVM, LVMIs, LVRWT,
      and LVEF as markers of cardiac TOI obtained in healthy children and adolescents.
      These data are valuable in that they provide RIs values with which data of
      populations of children, adolescents can be compared.

PMID- 30288600
TI  - Respiratory Testing and Hospital Outcomes in Asymtomatic Infants Undergoing Heart
      Surgery.
AB  - Respiratory viral infections in infants undergoing congenital heart surgery lead
      to prolonged intubation time, hospital (HLOS) and cardiac intensive care unit
      length of stay (CICU LOS). The objective of this study was to evaluate the
      prevalence of respiratory viruses using molecular testing in otherwise healthy
      infants presenting for low complexity heart surgery, and to evaluate the impact
      of a positive viral screen and study questionnaire on post-surgical HLOS, CICU
      LOS, intubation time, respiratory complications, and oxygen therapy at home
      discharge. Sixty-nine infants (1 month to 1 year) undergoing cardiac surgery from
      November to May of the years 2012 to 2014 were prospectively enrolled, surveyed
      and tested. We compared the outcomes of positive molecular testing and positive
      study questionnaire to test negative subjects. We also evaluated the predictive
      value of study questionnaire in identification of viruses by molecular testing.
      Of the 69 enrolled infants, 58 had complete information available for analysis.
      17 (30%) infants tested positive by molecular testing for respiratory pathogens.
      38 (65%) had a "positive" questionnaire. Among the 20 viruses detected, Human
      Rhinovirus was the most common 12 (60%). Seven (12%) of the 58 patients developed
      respiratory symptoms following surgery prompting molecular testing. Four of these
      tested positive for a respiratory virus post-surgically. Neither positive
      molecular testing nor a positive questionnaire prior to surgery was associated
      with greater post-operative HLOS, CICU LOS, intubation time, respiratory
      complications, or use of oxygen at discharge compared to negative testing. The
      questionnaire poorly predicted positive molecular testing. Routine screening for
      respiratory viruses in asymptomatic infants may not be an effective strategy to
      predict infants at risk of post-operative complications.

PMID- 30288601
TI  - [Tips and tricks for endoscopic negative pressure therapy. German version].
AB  - Endoscopic negative-pressure therapy (ENPT) is becoming a valuable tool in
      surgical complication management of transmural intestinal defects and wounds in
      the upper and lower gastrointestinal tract. Innovative materials for drains have
      been developed, endoscopic techniques adapted, and new indications for ENPT have
      been found. Based on our broad clinical experience, numerous tips and tricks are
      described, which contribute to the safety of dealing with the new therapy. The
      aim of this work is to present these methods. The focus is on describing the
      treatment in the esophagus.

PMID- 30288602
TI  - Exercise improves functional capacity and lean body mass in patients with
      gastrointestinal cancer during chemotherapy: a single-blind RCT.
AB  - PURPOSE: Although growing evidence underlines the benefits of physical activity
      as supportive intervention for cancer patients, sparse data are available for
      exercise in patients with advanced disease stages, in particular for
      gastrointestinal cancer (GIC) patients who experience specific disease-associated
      limitations. Thus, the aim of this study is to evaluate the effects of home-based
      moderate intensity exercise on functional capacity, activities of daily living
      (ADL) and body composition in patients with advanced GIC during first-line
      chemotherapy. METHODS: Participants (GIC, UICC III-IV; n = 44) were randomly
      assigned to home-based physical activity programme of 150 min moderate walking
      per week or a control group (CG). Functional status (SPPB: gait speed, balance,
      lower extremity muscle strength), postural sway, chemotherapy-induced peripheral
      neuropathy, nutritional state (Mini Nutritional Assessment, MNA) and lean body
      mass were assessed according to established recommendations. All tests were
      performed before chemotherapy (T0), after two chemotherapy cycles (T1) and after
      12 weeks (T2). RESULTS: SPPB changes from T1 to T2 differed between groups with a
      comparably greater decrease in the CG (p < .05), but no changes or group
      differences over the whole study period (T0 to T2) were found. Exercise improved
      postural sway (T0 to T1; T0 toT2) and lean body mass (T1 to T2; T0 to T2)
      compared to the control group (p < .05). Gait speed, peripheral neuropathy and
      strength did not differ between groups (p > .05). CONCLUSIONS: Our results
      indicate that a home-based physical activity improves postural sway and body
      composition and might stabilize functional capacity in patients with advanced GIC
      during chemotherapy. Although the other outcomes did not differ between groups,
      aforementioned effects might contribute to a maintenance of independency in ADL
      and a better treatment tolerance and thus enhance patients' quality of life.

PMID- 30288603
TI  - A conformationally restricted GABA analogue based on octahydro-1H
      cyclopenta[b]pyridine scaffold.
AB  - An approach to rel-(4aS,6R,7aR)-octahydro-1H-cyclopenta[b]pyridine-6-carboxylic
      acid-a bicyclic conformationally restricted gamma-aminobutyric acid (GABA)
      analogue was developed. The eight-step sequence relied on the reaction of 2,3
      bis(chloromethyl)pyridine and a C1-binucleophile and the catalytic reduction of
      the pyridine ring as the key steps and allowed for the preparation of the title
      compound in 9.0% overall yield. Assessment of the octahydro-1H
      cyclopenta[b]pyridine scaffold geometry showed that this template can be
      considered truly three-dimensional.

PMID- 30288604
TI  - Ensembling three multicomponent reactions for the synthesis of a novel category
      of pseudo-peptides containing dithiocarbamate and N,X-heterocylic groups.
AB  - Consecutive multicomponent reactions have been applied for the synthesis of novel
      pseudo-peptides bearing dithiocarbamate and N,X-heterocyclic groups (X = S, O) in
      only one structure. The first multicomponent reaction includes the synthesis of
      dithiocarbamates using an amine or amino acid, CS2 and an electrophile. The
      second MCR is synthesis of Asinger imines using 2-chloroisobutyraldehyde, NaXH (X
      = S, O), ketone and ammonia. The final MCR is Ugi reaction to afford the
      corresponding three-dimensional pseudo-peptides. Various Asinger imines,
      carboxylic acids and isocyanides were applied in this protocol to provide
      diversities of pseudo-peptides in high to excellent yields.

PMID- 30288605
TI  - Stress distribution in mandibular donor site after harvesting bone grafts of
      various sizes from the ascending ramus of a dentate mandible by finite element
      analysis.
AB  - PURPOSE: Harvesting bone from the ascending ramus of the mandible is a common
      procedure. However, mandibular fracture may occur after grafting bone blocks.
      This study aimed to investigate the resulting force distribution of stress and
      strain in the mandibular donor site after harvesting bone grafts of different
      sizes and various loadings. METHODS: Finite element analysis was performed for
      virtual harvesting of bone blocks of nine different sizes between 15 * 20 and 25
      * 30 mm and three different chewing loads (incisal, ipsilateral and
      contralateral). von Mises stress and first principal stress distributions were
      measured. RESULTS: von Mises stress was distributed between 35.01 (10 * 15 mm
      graft, incisal load) and 333.25 MPa (30 * 20 mm graft ipsilateral load), whereas
      first principal stress distributions were between 48.27 (10 * 15 mm graft,
      incisal load) and 414.69 MPa (30 * 20 mm graft ipsilateral load). In general, the
      least stress was observed with incisal load followed by ipsilateral load and
      finally contralateral load. The critical value of 133 MPa was found after
      removing almost all grafts with a width of 20 or 30 mm. CONCLUSIONS: Incisal
      loading led to less stress compared with contralateral and ipsilateral loads.
      Increasing graft size led to increasing weakness of the donor site. Graft width
      exerted a greater influence on stress development than its height. CLINICAL
      RELEVANCE: Ipsilateral chewing and increasing width of the bone graft result in
      maximum stress in the mandibular donor side, and critical values regarding to the
      possibility of fractures are already to expect from a graft size of 20 * 15 mm.

PMID- 30288606
TI  - Distances of root apices to adjacent anatomical structures in the anterior
      maxilla: an analysis using cone beam computed tomography.
AB  - OBJECTIVES: The aim was to assess the anatomical relationship of anterior
      maxillary teeth to the nasal floor in patients referred for apical surgery.
      MATERIALS AND METHODS: Cone beam computed tomographic images (CBCT) of 83
      patients were analysed retrospectively to quantify the distances between the root
      apices of maxillary anterior teeth (canine to canine) to the nasal floor or
      maxillary sinus (whichever was closer). Secondary outcome variables were the
      distances of the periapical lesion to the nasal floor, distances of the apices to
      the labial and palatal bone plates as well as to the neighbouring teeth. RESULTS:
      A total of 93 teeth (39 central, 35 lateral incisors and 19 canines) were
      analysed. The mean shortest distances of the apices to the nasal floor (or
      maxillary sinus) were 8.54 mm for central incisors, 9.49 mm for lateral incisors
      and 5.39 mm for the canines. The canines exhibited a significantly shorter
      distance to the nasal floor/maxillary sinus. In the presence of an osteolysis,
      the distance to the nasal floor was significantly shorter compared to the teeth
      without lesions. The lateral and central incisors showed significant proximity to
      each other at the level of the future surgical resection (3 mm from the apex).
      CONCLUSIONS: A close proximity between apices and adjacent anatomical structures
      such as nasal floor, maxillary sinus or adjacent roots could be shown in some
      cases. CLINICAL RELEVANCE: CBCT could be a valuable adjunctive imaging tool prior
      to apical surgery in the anterior maxilla to assess the risk for and decrease the
      incidence of damage to neighbouring anatomical structures such as the nasal
      floor, maxillary sinus or adjacent roots.

PMID- 30288607
TI  - Alstroemeria yellow spot virus (AYSV): a new orthotospovirus species within a
      growing Eurasian clade.
AB  - An orthotospovirus distinct from all other orthotospoviruses was isolated from
      naturally infected alstroemeria plants. Disease symptoms caused by this virus
      mainly consisted of yellow spots on the leaves based on which the name
      alstroemeria yellow spot virus (AYSV) was coined. A host range analysis was
      performed and a polyclonal antiserum was produced against purified AYSV
      ribonucleoproteins which only reacted with the homologous antigen and not with
      any other (established or tentative) orthotospovirus from a selection of American
      and Asian species. Upon thrips transmission assays the virus was successfully
      transmitted by a population of Thrips tabaci. The entire nucleotide sequence of
      the M and S RNA segments was elucidated by a conventional cloning and sequencing
      strategy, and contained 4797 respectively 2734 nucleotides (nt). Simultaneously,
      a next generation sequencing (NGS) approach (RNAseq) was employed and generated
      contigs covering the entire viral tripartite RNA genome. In addition to the M and
      S RNA nucleotide sequences, the L RNA (8865 nt) was obtained. The nucleocapsid
      (N) gene encoded by the S RNA of this virus consisted of 819 nucleotides with a
      deduced N protein of 272 amino acids and by comparative sequence alignments to
      other established orthotospovirus species showed highest homology (69.5%
      identity) to the N protein of polygonum ringspot virus. The data altogether
      support the proposal of AYSV as a new orthotospovirus species within a growing
      clade of orthotospoviruses that seem to share the Middle East basin as a region
      of origin.

PMID- 30288609
TI  - Alison Butler: papers in celebration of her 2018 ACS Alfred Bader Award in
      Bioorganic or Bioinorganic Chemistry.

PMID- 30288608
TI  - Nitrogen enrichment in host plants increases the mortality of common Lepidoptera
      species.
AB  - The recent decline of Lepidoptera species strongly correlates with the increasing
      intensification of agriculture in Western and Central Europe. However, the
      effects of changed host-plant quality through agricultural fertilization on this
      insect group remain largely unexplored. For this reason, we tested the response
      of six common butterfly and moth species to host-plant fertilization using
      fertilizer quantities usually applied in agriculture. The larvae of the study
      species Coenonympha pamphilus, Lycaena phlaeas, Lycaena tityrus, Pararge aegeria,
      Rivula sericealis and Timandra comae were distributed according to a split-brood
      design to three host-plant treatments comprising one control treatment without
      fertilization and two fertilization treatments with an input of 150 and 300 kg N
      ha-1 year-1, respectively. In L. tityrus, we used two additional fertilization
      treatments with an input of 30 and 90 kg N ha-1 year-1, respectively.
      Fertilization increased the nitrogen concentration of both host-plant species,
      Rumex acetosella and Poa pratensis, and decreased the survival of larvae in all
      six Lepidoptera species by at least one-third, without clear differences between
      sorrel- and grass-feeding species. The declining survival rate in all species
      contradicts the well-accepted nitrogen-limitation hypothesis, which predicts a
      positive response in species performance to dietary nitrogen content. In
      contrast, this study presents the first evidence that current fertilization
      quantities in agriculture exceed the physiological tolerance of common
      Lepidoptera species. Our results suggest that (1) the negative effect of plant
      fertilization on Lepidoptera has previously been underestimated and (2) that it
      contributes to the range-wide decline of Lepidoptera.

PMID- 30288610
TI  - Impact of a prenatal episode and diagnosis in women with serious mental illnesses
      on neonatal complications (prematurity, low birth weight, and hospitalization in
      neonatal intensive care units).
AB  - Pregnancy in women with mental disorders is increasingly common. The aim of this
      study was to determine, in women with severe mental illnesses, whether a prenatal
      episode was related to neonatal complications and if a specific disorder was
      associated with a higher risk. A population of infants and their mothers (n =
      1439) jointly admitted to psychiatric Mother-Baby Units in France and Belgium
      (2001-2010) was assessed respectively for prematurity, low birth weight (LBW),
      hospitalization in neonatal intensive care units (NICUs), and maternal mental
      health during pregnancy. Logistic regression was used to explore the association
      between neonatal complications and a prenatal episode of mental illness and if
      the presence of a specific disorder was related to a higher risk, taking into
      account maternal socio-demographic characteristics, pregnancy data, and antenatal
      exposure to psychotropic drugs. Among the children, 145 (10.2%) were premature,
      226 (15.8%) had a LBW, and 348 (24.3%) have been hospitalized in neonatology. The
      presence of an episode of mental illness during pregnancy was linked to LBW (OR =
      2.21 [1.44-3.38]; p = 0.003) and NICU hospitalizations (OR = 1.53 [1.06-2.19], p
      = 0.002). Among diagnoses, the presence of a severe substance use disorder in
      these women was related to LBW (OR = 2.96 [1.49-5.85]; p = 0.002) and NICU (OR =
      2.88 [1.56-5.29]; p = 0.04). Our results underline the importance of systematic
      and early detection of psychiatric symptoms and substance use disorders during
      pregnancy in preventing neonatal complications in women with serious mental
      illness.

PMID- 30288611
TI  - In situ assessment of mitochondrial calcium transport in tobacco pollen tubes.
AB  - Pollen tubes require functional mitochondria in order to achieve fast and
      sustained growth. In addition, cell wall expansion requires a calcium gradient in
      the tube apex formed by a dedicated array of calcium pumps and channels. Most
      studies have traditionally focused on the molecular aspects of calcium
      interactions and transport across the pollen tube plasmalemma. However, calcium
      transients across mitochondrial membranes from pollen tubes are beginning to be
      studied. Here, we report the presence of a ruthenium red-sensitive mitochondrial
      calcium uniporter-like activity in tobacco pollen tubes with functional oxidative
      phosphorylation. The present study provides a framework to measure in situ
      specifics of mitochondrial transport and respiration in pollen tubes from
      different plants. The relevance of a mitochondrial calcium uniporter for pollen
      tube growth is discussed.

PMID- 30288613
TI  - Improving child and adolescent mental health care provision by scrutiny of
      national diagnostic practices: A call for increased international knowledge
      exchange.

PMID- 30288614
TI  - Investigating the effect of climatic parameters on mental disorder admissions.
AB  - The main objective of this study was to evaluate the role of climatic parameters
      and phenomena including the monthly number of dusty/rainy/snowy/foggy days,
      cloudiness (Okta), horizontal visibility, and barometric pressure (millibar) on
      major depressive disorder, bipolar, schizophrenia, and schizoaffective
      admissions. The monthly data related to the number of admissions in Farshchian
      hospital and climatic parameters from March 2005 to March 2017 were extracted.
      Random forest regression and dynamic negative binomial regression were used to
      examine the relationship between variables; the statistical significance was
      considered as 0.05. The number of dusty/rainy/snowy/foggy days, cloudiness, and
      the number of days with vision less than 2 km had a significant positive
      relationship with admissions due to schizophrenia (p < 0.05). Barometric pressure
      had a negative effect on schizophrenia admissions (p < 0.001). The number of
      dusty/rainy/snowy/foggy days and cloudiness had a significant effect on
      schizoaffective admissions (p < 0.05). Bipolar admissions were negatively
      associated with rainy days and positively associated with dusty days and
      cloudiness (p < 0.05). The number of rainy/dusty/snowy days and cloudiness had a
      positive significant effect on major depressive disorder admissions. The results
      of the present study confirmed the importance of climatic parameter variability
      for major depressive disorder, bipolar, schizophrenia, and schizoaffective
      admissions.

PMID- 30288615
TI  - Colorimetric determination of dopamine by exploiting the enhanced oxidase
      mimicking activity of hierarchical NiCo2S4-rGO composites.
AB  - A composite consisting of NiCo2S4 and reduced graphene oxide (rGO) was prepared
      via a hydrothermal process. Compared to individual NiCo2S4 nanomaterials or
      reduced graphene oxide, the composite exhibits enhanced oxidase-like activity. It
      is found that dopamine (DA) inhibits the ability of NiCo2S4-rGO to oxidize the
      substrate 3,3',5',5'-tetramethylbenzidine (TMB) to form blue colored ox-TMB.
      Based on these findings, a colorimetric method for determination of DA was worked
      out. The absorption, best measured at 652 nm, increases linearly in the 0.5-100
      MUM DA concentration range, and the limit of detection is 0.42 MUM. This method
      was successfully applied to the detection of DA in spiked human serum samples.
      Graphical abstract A hierarchical NiCo2S4-rGO composite was prepared through two
      step hydrothermal process. It exhibits enhanced oxidase-like activity which,
      however, is inhibited by dopamine (DA). Hence, less blue colored ox-TMB is formed
      by oxidation of 3,3',5,5'-tetramethylbenzidine in the presence of dopamine.

PMID- 30288616
TI  - Medical Image Quality Assessment Using CSO Based Deep Neural Network.
AB  - This manuscript proposed a hybrid method of Deep Neural Network (DNN) and Cuckoo
      Search Optimization (CSO) with No-Reference Image Quality Assessment (NR-IQA) for
      achieving high accuracy, low computational complexity, flexibility and etc. of a
      medical image. NR-IQA is proposed due to till now there is no perfect reference
      image for finding the quality of real time medical imaging. It is an effective
      method for assessing the real-world medical images. The proposed method takes the
      distorted image as an input and estimate the quality of the image without the
      assistance of reference image. The techniques CSO and DNN with NR-IQA produces
      the quality of the image with high quality score and low Mean Square Error (MSE).
      Also, the proposed method is used to improve the quality score thereby improving
      the quality of the image. So that the resultant image has good visual properties
      which is useful for the analysis of further medical proceedings. The simulation
      result shows that the proposed system improves the quality score by 8% when
      compared to the other existing systems. The SROCC value can be increased as 6%,
      14%, 6 and 2% for the different existing methods such as NR-BIQA, SBVQP-ML,
      PTQL/PTVC and NR-SIQA (3D) respectively.

PMID- 30288617
TI  - Long-term outcomes after prophylactic use of onlay mesh in midline laparotomy.
AB  - BACKGROUND: The prevalence of incisional hernias (IHs) is still high after
      midline laparotomy (ML). There is an increasing body of evidence that
      prophylactic mesh placement (PMP) can be safe and efficient in the short-term
      outcomes, but there still are some concerns about the potential long-term
      complications of these meshes. This study describes our long-term PMP experience.
      METHODS: Observational and prospective study including all patients undergoing
      the use of prophylactic onlay large-pore polypropylene meshes for the closure of
      ML since 2008 to 2014. Outcome measures included demographics, perioperative
      details, wound complications, recurrences, reoperations and chronic
      complications. RESULTS: A cohort of 172 patients was analysed: 75% elective
      surgery, 25% emergency cases. Mean age was 68 years with mean body mass index
      (BMI) of 28.6 kg/m2. Wound classification: 6.4% clean; 85% clean-contaminated;
      1.2% contaminated and 8.1% dirty. Follow-up of patients was up to 8 years (mean:
      5 +/- 1.6). Two meshes were removed due to chronic infection in first six
      postoperative months. Of the 13 patients (9.02%) who developed IH, 5 of them have
      been reoperated for IH repair without any difficulty related to previous mesh.
      During follow-up, 8 patients have been reoperated for other reasons and the
      integrity of abdominal wall was also checked. After the comparative study, higher
      BMI and emergency surgery were still risk factors for IH despite PMP.
      CONCLUSIONS: In our setting, the use of polypropylene prophylactic meshes in MLs
      is safe, efficient and durable.

PMID- 30288618
TI  - Antimicrobial and Cytotoxicity Effects of Synthesized Silver Nanoparticles from
      Punica granatum Peel Extract.
AB  - To address the growing challenges from drug-resistant microbes and tumor
      incidence, approaches are being undertaken to phytosynthesize metal
      nanoparticles, particularly silver nanoparticles, to get remedial measure. In
      this study, an attempt has been made to utilize a major biowaste product,
      pomegranate fruit peel (Punica granatum), to synthesize silver nanoparticles. The
      silver nanoparticles (AgNPs) were synthesized using the aqueous extract of
      pomegranate peel. The formation of synthesized AgNPs was confirmed through UV-Vis
      spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM),
      scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy
      (EDX) as well as through the change of the colorless aqueous solution to a dark
      brown solution. Using UV-Vis spectroscopy, the dark brown solution showed a
      Plasmon resonance band peak at 378 nm in UV-Vis spectroscopy after reacting for
      24, 48, and 72 h. The XRD report revealed that the AgNPs had a cubic structure.
      The TEM and SEM report showed the nanoparticles were equally distributed in the
      solution, with a spherical shape and size ranging from 20 to 40 nm and with an
      average particle size of 26.95 nm. EDX imaging also confirmed the presence of
      AgNPs. The synthesized AgNPs were found to exhibit good antimicrobial effects on
      Gram-negative and Gram-positive bacteria, particularly the pathogens Escherichia
      coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27584), Proteus vulgaris (ATCC
      8427), Salmonella typhi (ATCC 14028), Staphylococcus aureus (ATCC 29213),
      Staphylococcus epidermidis (MTCC 3615), and Klebsiella pneumonia. The cytotoxic
      effects of AgNPs were also tested against a colon cancer cell line (RKO: ATCC(r)
      CRL-2577TM), and it was observed that the viabilities were 56% and 61% on days 3
      and 5, respectively, with exposure to 12.5 MUg of AgNPs. This simple, economic,
      and eco-friendly method suggests that the AgNPs biosynthesized using pomegranate
      peel extract may be a novel, potent solution for the development of a drug for
      colon cancer that also has antibacterial activity.

PMID- 30288619
TI  - Efficient Trilayer Phosphorescent Organic Light-Emitting Devices Without
      Electrode Modification Layer and Its Working Mechanism.
AB  - At present, numerous functional layers are introduced to improve the carrier
      injection and balance the carrier transport in organic light-emitting devices
      (OLEDs). Although it may be a good way to enhance the efficiency of devices, the
      introduction of functional layers would also result in extra process and long
      manufacture period. Actually, with the enrichment of material system, many
      appropriate materials could be chosen to share two or even more functions in
      OLEDs. Here, via impedance spectroscopy and transient electroluminescence
      analysis, di-[4-(N,N-ditolyl-amino)-phenyl] cyclohexane (TAPC) and 4,7-diphenyl
      1,10-phenanthroline (Bphen) are demonstrated to serve as carrier injection and
      transport layers simultaneously. As a result, efficient trilayer OLEDs are
      achieved with comparable performances to conventional multilayer devices. Further
      studies have also been carried out to analyze the recombination and quenching
      mechanisms in devices. TAPC can block electrons effectively, while Bphen avoids
      the accumulation of holes. It makes carriers in emitting layer become more
      balanced, resulting in the reduction of efficiency roll-off.

PMID- 30288620
TI  - Seed-Mediated Synthesis of Tunable-Aspect-Ratio Gold Nanorods for Near-Infrared
      Photoacoustic Imaging.
AB  - Tunable-aspect ratio gold nanorods have been synthesized by a modified seed
      mediated synthesis method. Ascorbic acid was employed as a shape controller to
      induce anisotropic growth, which made the aspect ratio of the synthesized gold
      nanorods range from 8.5 to 15.6. These nanorods possess tunable longitudinal
      surface plasmon resonance absorption band, covering a broad near-infrared (NIR)
      range, from ~ 680 to 1100 nm. When modified with thiol-polyethylene glycol (SH
      PEG), the synthesized Au nanorods showed excellent biocompatibility and
      stability, which foreshadowed the great potential of their NIR application as
      photoacoustic contrast agent. Due to their adjustable absorbance in the NIR, the
      synthesized Au nanorods could offer stronger contrast (3.1 times to the control
      group without contrast agent used) and higher signal-noise ratio values (SNR; 5.6
      times to the control group) in photoacoustic imaging, both in vitro and in vivo
      experiments. Our work presented here not only added some novel Au-based
      photoacoustic contrast agents but also described a possibility of contrast agent
      preparation covering the whole biological NIR window.

PMID- 30288621
TI  - Necrotizing fasciitis as a complication of osteonecrosis of the jaw related to
      oral bisphosphonate application in a patient with osteoporosis: a case report.
AB  - BACKGROUND: Necrotizing fasciitis has been reported as a complication secondary
      to bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a low number of
      patients. The only report of such a case in an osteoporosis patient found in
      current literature was related to short-term bisphosphonate but long time
      corticosteroid and methotrexate treatment. CASE PRESENTATION: In this article, we
      report a case of necrotizing fasciitis secondary to osteonecrosis of the jaw
      related to long-term oral bisphosphonate treatment in an osteoporosis patient
      additionally suffering from poorly controlled type 2 diabetes. Diabetes mellitus
      not only has been reported to be a systemic risk factor regarding BRONJ but also
      to be the most common comorbidity in patients presenting with necrotizing
      fasciitis and to increase mortality of this condition. Necrotizing fasciitis and
      BRONJ in the patient could eventually be resolved by a surgical approach and
      intravenous antibiotic therapy. CONCLUSIONS: The case presented suggests diabetes
      mellitus potentially having been an important factor in the particularly
      unfavorable course of therapy. It emphasizes the importance of an adequate
      therapy and surveillance of modifiable systemic risk factors like diabetes
      mellitus in patients being at risk for development of BRONJ. If necrotizing
      fasciitis is suspected, early diagnosis and aggressive surgical and medical
      management are essential to minimize morbidity and mortality.

PMID- 30288622
TI  - In-situ electrochemical analysis of microbial activity.
AB  - Microbes have a wide range of metabolic capabilities available that makes them
      industrially useful organisms. Monitoring these metabolic processes is a crucial
      component in efficient industrial application. Unfortunately, monitoring these
      metabolic processes can often be invasive and time consuming and expensive,
      especially within an anaerobic environment. Electrochemical techniques, such as
      cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) offer a
      non-invasive approach to monitor microbial activity and growth. EIS and CV were
      used to monitor Clostridium phytofermentans, an anaerobic and endospore-forming
      bacterium. C. phytofermentans ferments a wide range of sugars into hydrogen,
      acetate, and ethanol as fermentation by-products. For this study, both
      traditional microbiological and electrochemical techniques were used to monitor
      the growth of C. phytofermentans and the formation of fermentation products. An
      irreversible reduction peak was observed using CV beginning at mid-logarithmic
      phase of growth. This peak was associated with C. phytofermentans and not the
      spent medium and was indicative of a decrease in carbon and energy sources to the
      cells. Additionally, EIS analysis during growth provided information related to
      increased charge transfer resistance of the culture also as a function of carbon
      and energy source depletion. Results demonstrate that CV and EIS are useful tools
      in the monitoring the physiological status of bioprocesses.

PMID- 30288623
TI  - Rheumatology in and from Slovenia.

PMID- 30288624
TI  - Assessment of groundwater nitrate contamination hazard in a semi-arid region by
      using integrated parametric IPNOA and data-driven logistic regression models.
AB  - Groundwater hazard assessments involve many activities dealing with the impacts
      of pollution on groundwater, such as human health studies and environment
      modelling. Nitrate contamination is considered a hazard to human health,
      environment and ecosystem. In groundwater management, the hazard should be
      assessed before any action can be taken, particularly for groundwater pollution
      and water quality. Thus, pollution due to the presence of nitrate poses
      considerable hazard to drinking water, and excessive nutrient loads deteriorate
      the ecosystem. The parametric IPNOA model is one of the well-known methods used
      for evaluating nitrate content. However, it cannot predict the effect of soil and
      land use/land cover (LULC) types on calculations relying on parametric well
      samples. Therefore, in this study, the parametric model was trained and
      integrated with the multivariate data-driven model with different levels of
      information to assess groundwater nitrate contamination in Saladin, Iraq. The
      IPNOA model was developed with 185 different well samples and contributing
      parameters. Then, the IPNOA model was integrated with the logistic regression
      (LR) model to predict the nitrate contamination levels. Geographic information
      system techniques were also used to assess the spatial prediction of nitrate
      contamination. High-resolution SPOT-5 satellite images with 5 m spatial
      resolution were processed by object-based image analysis and support vector
      machine algorithm to extract LULC. Mapping of potential areas of nitrate
      contamination was examined using receiver operating characteristic assessment.
      Results indicated that the optimised LR-IPNOA model was more accurate in
      determining and analysing the nitrate hazard concentration than the standalone
      IPNOA model. This method can be easily replicated in other areas that have
      similar climatic condition. Therefore, stakeholders in planning and environmental
      decision makers could benefit immensely from the proposed method of this
      research, which can be potentially used for a sustainable management of urban,
      industrialised and agricultural sectors.

PMID- 30288626
TI  - Life beyond the Tanimoto coefficient: similarity measures for interaction
      fingerprints.
AB  - BACKGROUND: Interaction fingerprints (IFP) have been repeatedly shown to be
      valuable tools in virtual screening to identify novel hit compounds that can
      subsequently be optimized to drug candidates. As a complementary method to ligand
      docking, IFPs can be applied to quantify the similarity of predicted binding
      poses to a reference binding pose. For this purpose, a large number of similarity
      metrics can be applied, and various parameters of the IFPs themselves can be
      customized. In a large-scale comparison, we have assessed the effect of
      similarity metrics and IFP configurations to a number of virtual screening
      scenarios with ten different protein targets and thousands of molecules.
      Particularly, the effect of considering general interaction definitions (such as
      Any Contact, Backbone Interaction and Sidechain Interaction), the effect of
      filtering methods and the different groups of similarity metrics were studied.
      RESULTS: The performances were primarily compared based on AUC values, but we
      have also used the original similarity data for the comparison of similarity
      metrics with several statistical tests and the novel, robust sum of ranking
      differences (SRD) algorithm. With SRD, we can evaluate the consistency (or
      concordance) of the various similarity metrics to an ideal reference metric,
      which is provided by data fusion from the existing metrics. Different aspects of
      IFP configurations and similarity metrics were examined based on SRD values with
      analysis of variance (ANOVA) tests. CONCLUSION: A general approach is provided
      that can be applied for the reliable interpretation and usage of similarity
      measures with interaction fingerprints. Metrics that are viable alternatives to
      the commonly used Tanimoto coefficient were identified based on a comparison with
      an ideal reference metric (consensus). A careful selection of the applied bits
      (interaction definitions) and IFP filtering rules can improve the results of
      virtual screening (in terms of their agreement with the consensus metric). The
      open-source Python package FPKit was introduced for the similarity calculations
      and IFP filtering; it is available at: https://github.com/davidbajusz/fpkit .

PMID- 30288625
TI  - Facile Synthesis of Nitrogen-Doped Microporous Carbon Spheres for High
      Performance Symmetric Supercapacitors.
AB  - Nitrogen-doped microporous carbon spheres (NMCSs) are successfully prepared via
      carbonization and KOH activation of phenol-formaldehyde resin polymer spheres
      synthesized by a facile and time-saving one-step hydrothermal strategy using
      triblock copolymer Pluronic F108 as a soft template under the Stober-like method
      condition. The influence of the ethanol/water volume ratios and carbonation
      temperatures on the morphologies, pore structures and electrochemical
      performances of the prepared NMCSs are investigated systematically. The optimal
      NMCSs have a large specific surface area of 1517 m2 g- 1 with a pore volume of
      0.8 cm3 g- 1. The X-ray photo-electron spectroscopy analysis reveals a suitable
      nitrogen-doped content of 2.6 at.%. The as-prepared NMCSs used as supercapacitor
      electrode materials exhibit an outstanding specific capacitance of 416 F g- 1 at
      a current density of 0.2 A g- 1, also it shows an excellent charge/discharge
      cycling stability with 96.9% capacitance retention after 10,000 cycles. The
      constructed symmetric supercapacitors using PVA/KOH as the gel electrolyte can
      deliver a specific capacitance of 60.6 F g- 1 at current density of 1 A g- 1. A
      maximum energy density of 21.5 Wh kg- 1 can be achieved at a power density of 800
      W kg- 1, and the energy density still maintains 13.3 Wh kg- 1 even at a high
      power density of 16 kW kg- 1. The results suggest that this work can open up a
      facile and effective way to synthesize the NMCSs for electrode materials of high
      performance energy storage devices.

PMID- 30288627
TI  - Graphene-Based Nanoscale Vacuum Channel Transistor.
AB  - We report the fabrication and electrical performance of nanoscale vacuum channel
      transistor (NVCT) based on graphene. Ninety-nanometer-width vacuum nano-channel
      could be precisely fabricated with standard electron beam lithography process.
      The optimization and treatment of surface damage and adhesive residue on graphene
      are carried out by ultrasonic cleaning and thermal annealing. Additionally, in
      situ electric characteristics are directly performed inside a vacuum chamber of
      scanning electron microscope (SEM) with the nanomanipulator. By modulating the
      gate voltage, the NVCT could be switched from off-state to on-state, exhibiting
      an on/off current ratio up to 102 with low working voltages (< 20 V) and leakage
      current (< 0.5 nA). Furthermore, the nanoscale vacuum channel could enable to
      scale down the size of vacuum devices with high integration, making NVCT a
      promising candidate for high speed applications.

PMID- 30288628
TI  - Efficient Photocatalysts Made by Uniform Decoration of Cu2O Nanoparticles on Si
      Nanowire Arrays with Low Visible Reflectivity.
AB  - Highly uniformed decorations of Cu2O nanoparticles on the sidewalls of silicon
      nanowires (SiNWs) with high aspect ratio were prepared through a two-step
      electroless deposition at room temperature. Morphology evolutions and
      photocatalytic performance of SiNWs decorated with aggregated and dispersed Cu2O
      nanoparticles were unveiled, and the correlated photodegradation kinetics was
      identified. In comparison with the conventional direct loadings where the
      aggregated Cu2O/SiNW structures were created, the uniform incorporation of Cu2O
      with SiNWs exhibited more than three and nine times of improved photodegradation
      efficiency than the aggregated-Cu2O/SiNWs and sole SiNWs, respectively.

PMID- 30288630
TI  - N-Terminal Fusion Potentiates alpha-Synuclein Secretion.

PMID- 30288629
TI  - Long-term results after stapled hemorrhoidopexy: a survey study with mean follow
      up of 12 years.
AB  - BACKGROUND: Hemorrhoidal prolapse is a common benign disease. The introduction of
      circular-stapled hemorrhoidopexy as an alternative to the conventional
      hemorrhoidectomy led to a new spectrum of postoperative outcomes and
      complications. The aim of the present study was to evaluate long-term results
      after stapled hemorrhoidopexy. METHODS: All the patients who had stapled
      hemorrhoidopexy using a PPH03 stapler, from January 2003 to December 2005, were
      retrospectively collected in a dedicated database. Between March and May 2016,
      all the patients were asked by phone to complete a questionnaire. The study
      evaluated anatomical recurrence, symptom recurrence and frequency, and
      satisfaction after surgery. The postoperative complications recorded were
      hemorrhage, hematoma, urinary retention, anastomotic stenosis, persistent anal
      pain, tenesmus, and impaired anal continence evaluated also with the Faecal
      Incontinence Severity Index score. RESULTS: One hundred and ninety four patients
      were identified and 171 completed the questionnaire. The mean follow-up was 12 +/
      0.8 years (range 11-13 years). Anatomical self-reported prolapse recurrence was
      40.9% (n = 70). In 75.6% (n = 129) of patients, the severity and frequency of
      symptoms improved. The overall complication rate was 56.7% (n = 40) with a
      serious adverse event rate of 8.7% (n = 15). The overall tenesmus rate was 38.2%
      (n = 65) and the overall impaired continence rate was 39.1% (n = 67). Medical
      therapy was still required occasionally by 40.3% (n = 69) of the patients and
      9.3% (n = 16) of the patients underwent surgery for recurrence. Patient
      satisfaction rate was good (>= 3 on a scale of 1 to 5) in 81.2% (n = 139) of
      cases. CONCLUSIONS: The study showed that stapled hemorrhoidopexy using the first
      generation devices is safe and feasible but associated with a high recurrence and
      incontinence rate. More stringent selection criteria in association with the use
      of large volume devices can lead to better results in the future.

PMID- 30288632
TI  - The biology of ageing and the omics revolution.

PMID- 30288633
TI  - Molecular cloning, tissue distribution, and pharmacological characterization of
      blunt snout bream (Megalobrama amblycephala) melanocortin-5 receptor.
AB  - The melanocortin-5 receptor (MC5R) plays an important role in the regulation of
      exocrine secretion in mammals. Its function in fish is not well established. In
      this study, we reported the molecular cloning, tissue expression, and
      pharmacological characterization of Megalobrama amblycephala MC5R (MamMC5R), as
      well as the effect of catching stress on its expression. The full-length cDNA of
      Mammc5r gene was 1237 bp, consisted of a 990-bp open reading frame encoding 329
      amino acids. Sequence analyses revealed that the nucleotide and amino acid
      sequences of Mammc5r were highly homologous (> 90%) with MC5Rs of zebrafish,
      common carp, and goldfish. Tissue expression profile analysis showed that Mammc5r
      was widely expressed in both central and peripheral tissues, with the highest
      expression in the brain. Catching stress significantly changed the expression of
      Mammc5r in the skin, brain, and eye. In the skin, the expression level of Mammc5r
      was significantly reduced at 1 h and 4 h and increased at 24 h after catching
      stress. The Mammc5r expression level was rapidly upregulated in the brain and eye
      at 1 h and then decreased to the level before stress at 4 h and 24 h. With human
      MC5R (HsaMC5R) as a control, several agonists including alpha-melanocyte
      stimulating hormone (alpha-MSH), and beta-MSH in addition to an analogue [Nle4, D
      Phe7]-alpha-MSH (NDP-MSH), were used to investigate the binding and signaling
      properties of MamMC5R. The results revealed that MamMC5R had the highest affinity
      for NDP-MSH, followed by alpha- and beta-MSH. Taken together, the data suggested
      that MamMC5R might play a role in stress response in M. amblycephala.

PMID- 30288631
TI  - Secretion and Uptake of alpha-Synuclein Via Extracellular Vesicles in Cultured
      Cells.
AB  - In Parkinson's disease and other Lewy body disorders, the propagation of
      pathology has been accredited to the spreading of extracellular alpha-synuclein
      (alpha-syn). Although the pathogenic mechanisms are not fully understood, cell-to
      cell transfer of alpha-syn via exosomes and other extracellular vesicles (EVs)
      has been reported. Here, we investigated whether altered molecular properties of
      alpha-syn can influence the distribution and secretion of alpha-syn in human
      neuroblastoma cells. Different alpha-syn variants, including alpha-syn:hemi-Venus
      and disease-causing mutants, were overexpressed and EVs were isolated from the
      conditioned medium. Of the secreted alpha-syn, 0.1-2% was associated with
      vesicles. The major part of EV alpha-syn was attached to the outer membrane of
      vesicles, whereas a smaller fraction was found in their lumen. For alpha-syn
      expressed with N-terminal hemi-Venus, the relative levels associated with EVs
      were higher than for WT alpha-syn. Moreover, such EV-associated alpha-syn:hemi
      Venus species were internalized in recipient cells to a higher degree than the
      corresponding free-floating forms. Among the disease-causing mutants, A53T alpha
      syn displayed an increased association with EVs. Taken together, our data suggest
      that alpha-syn species with presumably lost physiological functions or altered
      aggregation properties may shift the cellular processing towards vesicular
      secretion. Our findings thus lend further support to the tenet that EVs can
      mediate spreading of harmful alpha-syn species and thereby contribute to the
      pathology in alpha-synucleinopathies.

PMID- 30288634
TI  - Selective Enzymatic Digestion of Proteoglycans and Collagens Alters Cartilage
      T1rho and T2 Relaxation Times.
AB  - Our objective was to determine the relationship of T1rho and T2 relaxation
      mapping to the biochemical and biomechanical properties of articular cartilage
      through selective digestion of proteoglycans and collagens. Femoral condyles were
      harvested from porcine knee joints and treated with either chondroitinase ABC
      (cABC) followed by collagenase, or collagenase followed by cABC. Magnetic
      resonance images were acquired and cartilage explants were harvested for
      biochemical, biomechanical, and histological analyses before and after each
      digestion. Targeted enzymatic digestion of proteoglycans with cABC resulted in
      elevated T1rho relaxation times and decreased sulfated glycosaminoglycan content
      without affecting T2 relaxation times. In contrast, extractable collagen and T2
      relaxation times were increased by collagenase digestion; however, neither was
      altered by cABC digestion. Aggregate modulus decreased with digestion of both
      components. Overall, we found that targeted digestion of proteoglycans and
      collagens had varying effects on biochemical, biomechanical, and imaging
      properties. T2 relaxation times were altered with changes in extractable
      collagen, but not changes in proteoglycan. However, T1rho relaxation times were
      altered with proteoglycan loss, which may also coincide with collagen disruption.
      Since it is unclear which matrix components are disrupted first in
      osteoarthritis, both markers may be important for tracking disease progression.

PMID- 30288635
TI  - Alveolar Macrophage Chemokine Secretion Mediates Neutrophilic Lung Injury in Nox2
      Deficient Mice.
AB  - Acute lung injury (ALI), developing as a component of the systemic inflammatory
      response syndrome (SIRS), leads to significant morbidity and mortality. Reactive
      oxygen species (ROS), produced in part by the neutrophil NADPH oxidase 2 (Nox2),
      have been implicated in the pathogenesis of ALI. Previous studies in our
      laboratory demonstrated the development of pulmonary inflammation in Nox2
      deficient (gp91phox-/y) mice that was absent in WT mice in a murine model of
      SIRS. Given this finding, we hypothesized that Nox2 in a resident cell in the
      lung, specifically the alveolar macrophage, has an essential anti-inflammatory
      role. Using a murine model of SIRS, we examined whole-lung digests and
      bronchoalveolar lavage fluid (BALf) from WT and gp91phox-/y mice. Both genotypes
      demonstrated neutrophil sequestration in the lung during SIRS, but neutrophil
      migration into the alveolar space was only present in the gp91phox-/y mice.
      Macrophage inflammatory protein (MIP)-1alpha gene expression and protein
      secretion were higher in whole-lung digest from uninjected gp91phox-/y mice
      compared to the WT mice. Gene expression of MIP-1alpha, MCP-1, and MIP-2 was
      upregulated in alveolar macrophages obtained from gp91phox-/y mice at baseline
      compared with WT mice. Further, ex vivo analysis of alveolar macrophages, but not
      bone marrow-derived macrophages or peritoneal macrophages, demonstrated higher
      gene expression of MIP-1alpha and MIP-2. Moreover, isolated lung
      polymorphonuclear neutrophils migrate to BALf obtained from gp91phox-/y mice,
      further providing evidence of a cell-specific anti-inflammatory role for Nox2 in
      alveolar macrophages. We speculate that Nox2 represses the development of
      inflammatory lung injury by modulating chemokine expression by the alveolar
      macrophage.

PMID- 30288636
TI  - Statins Inhibit Cytokines in a Dose-Dependent Response in Patients with Systemic
      Sclerosis.
AB  - Although statins have been successfully administered in the treatment of
      hypercholesterolemia and cardiovascular disease due to their lipid-lowering and
      anti-atherosclerotic action, they have shown immunomodulatory effects in several
      studies with immune-mediated diseases. The aim of this study was to investigate
      the effects of statins treatment on Th1, Th2, and Th17 cytokines production from
      stimulated peripheral blood mononuclear cells (PBMCs) obtained from Systemic
      Sclerosis (SSc) patients. We recruited 21 patients classified according to the
      American College of Rheumatology criteria for SSc for PBMCs culture analysis.
      Cytokine levels (IL-2, IL-4, IL-6, IL-10, TNF, IFN-gamma, IL-17A, and IL-17F)
      were quantified by ELISA or CBA, and patients were assessed for clinical and
      exam's variables. Simvastatin and atorvastatin at 50 MUM promoted reduction in
      all cytokine levels with statistical significance, except for IL-6, which had its
      reduction only induced by the use of simvastatin. Statins, particularly
      simvastatin, appear to have an immunosuppressive effect in reducing all cytokine
      secretion levels from PBMCs of SSc in a dose-dependent manner.

PMID- 30288637
TI  - Ultrasound evaluation of fetal critical aortic stenosis using the left atrium
      area/cardiac area ratio and the Doppler patterns in the pulmonary veins.
AB  - In fetal critical aortic stenosis (AS), a double reverse pattern in the pulmonary
      veins (PVs) is associated with a poor prognosis. We evaluated the hemodynamic
      changes using PV Doppler and the left atrium area/cardiac area (LA/CA) ratio in a
      fetus at 28 weeks of gestation with critical AS complicated with hydrops fetalis,
      polyhydramnios, and cardiac abnormality. A markedly enlarged LA and severe mitral
      regurgitation with critical AS were detected, with LA/CA ratio = 0.40 and double
      reverse pattern with forward/reverse velocity time integral ratio (FRVR) = 1.18
      on PV Doppler. After amniotic reduction at 31 weeks, the LA/CA ratio decreased
      (0.24) and the FRVR in PV increased (7.11). Forward flow through the fetal aorta
      was seen spontaneously, and hydrops fetalis was relieved with LA volume
      reduction. A male neonate weighing 2171 g was delivered via cesarean section at
      36 weeks with an Apgar score of 5 and 6 at 1 and 5 min, respectively. He required
      atrial septal opening and bilateral pulmonary artery banding after birth,
      followed by Norwood operation. The double reverse pattern in PVs might be
      reversible. The change in FRVR in PVs and LA/CA ratio would be helpful in
      understanding the hemodynamic change in fetal critical AS.

PMID- 30288638
TI  - Ready player one? Autophagy shapes resistance to photodynamic therapy in cancers.
AB  - Photodynamic therapy (PDT) is a procedure used in cancer therapy that has been
      shown to be useful for certain indications. Considerable evidence suggests that
      PDT might be superior to conventional modalities for some indications. In this
      report, we examine the relationship between PDT responsiveness and autophagy,
      which can exert a cytoprotective effect. Autophagy is an essential physiological
      process that maintains cellular homeostasis by degrading dysfunctional or
      impaired cellular components and organelles via a lysosome-based pathway.
      Autophagy, which includes macroautophagy and microautophagy, can be a factor that
      decreases or abolishes responses to various therapeutic protocols. We
      systematically discuss the mechanisms underlying cell-fate decisions elicited by
      PDT; analyse the principles of PDT-induced autophagy, macroautophagy and
      microautophagy; and present evidence to support the notion that autophagy is a
      critical mechanism in resistance to PDT. A combined strategy involving autophagy
      inhibitors may be able to further enhance PDT efficacy. Finally, we provide
      suggestions for future studies, note where our understanding of the relevant
      molecular regulators is deficient, and discuss the correlations among PDT-induced
      resistance and autophagy, especially microautophagy.

PMID- 30288639
TI  - TAK1 mediates convergence of cellular signals for death and survival.
AB  - TGF-beta activated kinase 1, a MAPK kinase kinase family serine threonine kinase
      has been implicated in regulating diverse range of cellular processes that
      include embryonic development, differentiation, autophagy, apoptosis and cell
      survival. TAK1 along with its binding partners TAB1, TAB2 and TAB3 displays a
      complex pattern of regulation that includes serious crosstalk with major
      signaling pathways including the C-Jun N-terminal kinase (JNK), p38 MAPK, and I
      kappa B kinase complex (IKK) involved in establishing cellular commitments for
      death and survival. This review also highlights how TAK1 orchestrates regulation
      of energy homeostasis via AMPK and its emerging role in influencing mTORC1
      pathway to regulate death or survival in tandem.

PMID- 30288640
TI  - Position and Content Paradigms in Genome Rearrangements: The Wild and Crazy World
      of Permutations in Genomics.
AB  - Modellers of large-scale genome rearrangement events, in which segments of DNA
      are inverted, moved, swapped, or even inserted or deleted, have found a natural
      syntax in the language of permutations. Despite this, there has been a wide range
      of modelling choices, assumptions and interpretations that make navigating the
      literature a significant challenge. Indeed, even authors of papers that use
      permutations to model genome rearrangement can struggle to interpret each others'
      work, because of subtle differences in basic assumptions that are often deeply
      ingrained (and consequently sometimes not even mentioned). In this paper, we
      describe the different ways in which permutations have been used to model genomes
      and genome rearrangement events, presenting some features and limitations of each
      approach, and show how the various models are related. This paper will help
      researchers navigate the landscape of permutation-based genome rearrangement
      models and make it easier for authors to present clear and consistent models.

PMID- 30288641
TI  - A Kinetic Analysis of Coupled (or Auxiliary) Enzyme Reactions.
AB  - As a case study, we consider a coupled (or auxiliary) enzyme assay of two
      reactions obeying the Michaelis-Menten mechanism. The coupled reaction consists
      of a single-substrate, single-enzyme non-observable reaction followed by another
      single-substrate, single-enzyme observable reaction (indicator reaction). In this
      assay, the product of the non-observable reaction is the substrate of the
      indicator reaction. A mathematical analysis of the reaction kinetics is
      performed, and it is found that after an initial fast transient, the coupled
      reaction is described by a pair of interacting Michaelis-Menten equations.
      Moreover, we show that when the indicator reaction is fast, the quasi-steady
      state dynamics are governed by three fast variables and one slow variable.
      Timescales that approximate the respective lengths of the indicator and non
      observable reactions, as well as conditions for the validity of the Michaelis
      Menten equations, are derived. The theory can be extended to deal with more
      complex sequences of enzyme-catalyzed reactions.

PMID- 30288642
TI  - Polymorphism distribution of RYR1, PRKAG3, HFABP, MYF-5 and MC4R genes in
      crossbred pigs.
AB  - This study was designed to screen the crossbred pigs for SNPs in five candidate
      genes, associated with pork quality traits and to differentiate their genotypes
      by PCR-RFLP. The results indicated that genotypes of crossbred pigs were NN (90%)
      and Nn (10%) for RYR1; RR (83%) and QR (17%) for PRKAG3; HH (98%), Hh (1%) and hh
      (1%) for HFABP; DD (99%) and CD (1%) for MYF-5; and AG (57%), GG (26%) and AA
      (17%) for MC4R SNPs, respectively. Allelic frequencies for five SNPs {RYR1
      (1843C>T), PRKAG3 (c.599G>A), HFABP (c.1322C>T), MYF-5 (c.1205A>C) and MC4R
      (c.1426A>G)} were 0.95 and 0.05 (N/n), 0.08 and 0.92 (Q/R), 0.99 and 0.01 (H/h),
      0.00 and 1.00 (C/D) and 0.45 and 0.55 (A/G), respectively. The effect of RYR1
      (1843C>T) SNP was significant on pH45 (P < 0.05), pH24 (P < 0.05) and protein %
      (P < 0.05). The PRKAG3 (c.599G>A) and MC4R (c.1426A>G) SNP had significant
      association with dressing percentages. The results revealed that RYR1, PRKAG3 and
      MC4R SNPs may be used in marker associated selection for pork quality traits in
      crossbred pigs.

PMID- 30288643
TI  - TCF4 and GRM8 gene polymorphisms and risk of schizophrenia in an Iranian
      population: a case-control study.
AB  - TCF4 and GRM8, two significant genes involved in the normal nervous development
      and glutamate pathway, are thought to be involved in the pathogenesis of
      schizophrenia (SCZ). We aimed to explore the association of TCF4 and GRM8 gene
      polymorphisms with risk of SCZ. The rs8766 in TCF4 and rs712723 in GRM8 were
      selected for genotyping in a set of Iranian case-control samples including 215
      patients and 220 matched healthy controls using polymerase chain reaction
      restriction fragment length polymorphism. Although rs8766 increased the OR, we
      found that rs8766 allele and genotype frequencies were not significantly
      different between case and control groups and a significant association cannot be
      suggested for the selected SNP. However, allele C and genotype CC (allele C: OR
      1.48, 95% CI 1.13-1.94; genotype CC: OR 1.71, 95% CI 1.09-2.68) of rs712723
      polymorphism was found to have a significant association with risk of SCZ.
      Frequency of allele C (P = 0.003) and genotype CC (P = 0.017) was higher in the
      schizophrenic patients, while allele T (P = 0.003) and genotype TT (P = 0.028)
      frequencies were found lower in patients. Our findings indicate that rs712723 in
      GRM8 may play an important role in the pathogenesis of SCZ. However, our
      conclusion needs to be confirmed in other population.

PMID- 30288644
TI  - SMER28 Attenuates Dopaminergic Toxicity Mediated by 6-Hydroxydopamine in the Rats
      via Modulating Oxidative Burdens and Autophagy-Related Parameters.
AB  - Parkinson's disease is the second most common neurodegenerative disease that
      occurs due to cellular autophagy deficiency and the accumulation of alpha
      synuclein in the dopaminergic neurons of the substantia nigra pars compacta (SNc)
      of the brainstem. The SMER28 (also known as 6-Bromo-N-prop-2-enylquinazolin-4
      amine) is an autophagy inducer. In this study, the neuroprotective effects of
      SMER28 were evaluated on autophagy induction, antioxidant system activation, and
      microgliosis attenuation. The Parkinson's disease model was developed in the male
      Wistar rats by injection of 6-OHDA into the left striatum. Apomorphine-induced
      behavior assessment test and SNc cell counting were performed to investigate the
      neuroprotective effects of SMER28. This study examined the pharmacological roles
      of SMER28, especially by focusing on the autophagy (p62/ SQSTM1 and LC3II/LC3I
      ratio where LC3 is microtubule-associated protein 1A/1B-light chain 3),
      inhibiting free radicals, and activating the antioxidant system. The levels of
      malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH),
      GSH/glutathione peroxidase (GPX), superoxide dismutase (SOD) activity and nuclear
      factor-erythroid 2-related factor-2 (Nrf2) were measured to evaluate the
      antioxidant activity of SMER28. Moreover, Iba-1 (ionized calcium binding adaptor
      molecule, indicating microgliosis) and tyrosine hydroxylase immunoreactivities
      were evaluated in the SNc. In the behavioral assessment, SMER28 (50 ug/kg)
      attenuated damages to the SNc dopaminergic neurons, characterized by improved
      motor function. The tissue observations revealed that SMER28 prevented the
      destruction of SNc neurons and attenuated microgliosis as well. It also reduced
      MDA and ROS production and increased GSH, GPX, SOD, and Nrf2 activities by
      inducing autophagy (decreasing p62 and increasing LC3II/LC3I ratio).
      Consequently, possibly with further studies, it can be considered as a drug for
      neurodegenerative diseases with proteinopathy etiology.

PMID- 30288645
TI  - Newborn Screening for IKBKB Deficiency in Manitoba, Using Genetic Mutation
      Analysis.

PMID- 30288646
TI  - Repeated Valsalva maneuvers promote symptomatic manifestations of cerebral
      microhemorrhages: implications for the pathogenesis of vascular cognitive
      impairment in older adults.
AB  - Multifocal cerebral microhemorrhages (CMHs, also known as "cerebral
      microbleeds"), which are associated with rupture of small intracerebral vessels,
      have been recognized as an important cause for cognitive decline in older adults.
      Although recent studies demonstrate that CMHs are highly prevalent in patients 65
      and older, many aspects of the pathogenesis and clinical significance of CMHs
      remain obscure. In this longitudinal observational study, a case of a 77-year-old
      man with multifocal CMHs is described, in whom the rupture of intracerebral
      vessels could be linked to repeatedly performing extended Valsalva maneuvers.
      This patient was initially seen with acute aphasia after performing a prolonged
      Valsalva maneuver during underwater swimming. T2-weighted magnetic resonance
      imaging revealed a left acute frontal intracerebral hemorrhage (ICH) with
      multiple CMHs. The aphasia was resolved and no cognitive impairment was present.
      Two years later, he developed unsteadiness and confusion after performing two
      prolonged Valsalva maneuvers during underwater swimming separated by about 12
      days. Repeat brain imaging revealed an acute right and a subacute left ICH, with
      a marked interval increase in the number of CMHs. The patient also exhibited
      manifest memory loss after the second admission and was diagnosed with dementia.
      These observations suggest that prolonged Valsalva maneuver is potentially a
      common precipitating cause of both CMHs and symptomatic ICHs. The Valsalva
      maneuver both increases the systolic arterial pressure and gives rise to a venous
      pressure wave transmitted to the brain in the absence of the competent antireflux
      jugular vein valves. This pressure increase is superimposed on existing
      hypertension and/or increases in blood pressure due to exercise and increased
      venous return due to immersion of the body in water. We advocate that further
      studies are needed to distinguish between CMHs with arterial and venous origins
      and their potential to lead to ICH induced by Valsalva maneuver as well as to
      determine whether these lesions have a predilection for a particular location.

PMID- 30288647
TI  - Distribution of polycyclic aromatic hydrocarbons (PAHs) in commonly consumed
      seafood from coastal areas of Bangladesh and associated human health
      implications.
AB  - Levels, distribution, possible sources and potential risks of 16 USEPA priority
      polycyclic aromatic hydrocarbons (PAHs) were investigated comprehensively in
      frequently consumed seafood species collected from the coastal areas of
      Bangladesh. Samples were collected in winter and summer, 2015. The total
      concentration of PAHs (?PAHs) in the examined seafood was 184.5-2806.6 ng/g wet
      weight (ww) in winter and 117.9-4216.8 ng/g ww in summer, respectively. The
      levels of ?PAHs were comparable to or higher than those reported from other
      coastal areas. Seasonal variation was not significant for the majority of the
      monitored PAHs. Spatial distribution revealed that the seafood collected from
      areas with recent urbanization and industrialization (Chittagong, Cox's Bazar and
      Sundarbans) was more contaminated with PAHs than those from the unindustrialized
      area (Meghna Estuary). Low-molecular-weight isomers dominated the PAH
      composition. Molecular ratios suggested the abundance of mixed sources of PAHs in
      the Bangladeshi coastal areas with a slight imposition toward the petrogenic
      origin. A preliminary evaluation of human health risk indicated that the dietary
      PAH exposure from consumption of Bangladeshi seafood would certainly induce
      adverse health effects. This finding suggests the need to enhance risk management
      regarding seafood consumption through public advisory in Bangladesh.

PMID- 30288648
TI  - Do Beliefs About Whether Others Can See Modulate Social Seeking in Autism?
AB  - Autistic people process gaze differently than typical people, but it is not yet
      clear if these differences lie in the processing of eye-shapes or the belief in
      whether others can see (perceptual mentalizing). We aimed to investigate whether
      these two models of gaze processing modulate social seeking in typical and
      autistic adults. We measured preferences of participants to view videos of an
      actress with visible or hidden eyes, who can or cannot see out. While typical
      participants preferred videos where the actress can see through and has visible
      eyes, autistic people showed no preference for these videos. These findings are
      discussed in the context of perceptual mentalizing and the social motivation
      theory of autism.

PMID- 30288650
TI  - ASO Author Reflections: Transoral Robotic Surgery Combined with Neoadjuvant
      Chemotherapy for Management of Advanced Laryngohypopharyngeal Cancer.

PMID- 30288651
TI  - ASO Author Reflections: Biomarkers for Neoadjuvant Chemoradiation Therapy in
      Esophageal Squamous Cell Carcinoma.

PMID- 30288649
TI  - Suture dehiscence and collagen content in the human mitral and tricuspid annuli.
AB  - Postoperative suture dehiscence is an important mode of short-term mitral and
      tricuspid valve (MV, TV) repair failure. We sought to evaluate suture pullout
      forces and collagen density in human atrioventricular valves for a better
      understanding of the comparative physiology between the valves and the underlying
      mechanobiological basis for suture retention. Mitral and tricuspid annuli were
      each excised from hearts from human donors age 60-79 with no history of heart
      disease (n = 6). Anchor sutures were vertically pulled until tearing through the
      tissue. Suture pullout force (FP) was measured as the maximum force at
      dehiscence. Subsequently, tissue samples from each tested suture position were
      evaluated for collagen content using a standard hydroxyproline assay. Among all
      mitral positions, no significant differences were detected among positions or
      regions with mean FP values falling between 6.9 +/- 2.6 N (posterior region) and
      10.3 +/- 4.7 N (anterior region). Among all tricuspid positions, the maximum FP
      and minimum FP were 24.0 +/- 9.2 N (trigonal region) and 4.5 +/- 2.6 N (anterior
      region). Although for the MV, a given sample's collagen content had no
      correlation to its corresponding FP, the same relationship was significant for
      the TV. Further, the TV exhibited comparable FP to the MV overall, despite a
      nearly 40% reduction in collagen content. These findings suggest that sutures
      placed in the trigonal region of the TV have higher pullout force than those
      placed along other segments of the annuli. Furthermore, there are likely
      differences in collagen orientation between the mitral and tricuspid annuli, such
      that collagen content strongly impacts FP in one, but not the other.

PMID- 30288652
TI  - ASO Author Reflections: Re-resection of Positive Bile Duct Margin for Hilar
      Cholangiocarcinoma.

PMID- 30288653
TI  - ASO Author Reflections: Peritoneal Metastases from Endometrial Cancer.

PMID- 30288655
TI  - ASO Author Reflections: Prolonged Immunoparalysis of NK Cells After Surgery.

PMID- 30288654
TI  - C-Reactive Protein Level Predicts Survival Outcomes in Rectal Cancer Patients
      Undergoing Total Mesorectal Excision After Preoperative Chemoradiation Therapy.
AB  - BACKGROUND: Systemic inflammatory response, as measured by C-reactive protein
      (CRP), is associated with prognosis in various types of human malignancies.
      However, to the best of our knowledge, the clinical significance of CRP in
      patients with locally advanced rectal cancer that undergo preoperative
      chemoradiation has not been investigated in detail. This retrospective study
      validates CRP as a potential predictive marker for survival outcomes in rectal
      cancer patients. METHODS: In this study, we enrolled 125 patients that received
      total mesorectal excision after preoperative chemoradiation for rectal cancer
      between January 2003 and December 2010. We investigated the association between
      preoperative CRP and clinicopathological characteristics and assessed the
      prognostic value of CRP. RESULTS: The median follow-up was 41 months. Elevated
      CRP showed significant correlation with high histological grade (P = 0.009) and
      cancer recurrence (P = 0.027). The 5-year disease-free survival and cancer
      specific survival were significantly lower in the elevated CRP group (P = 0.001).
      Moreover, CRP was the strongest predictive factor for cancer-specific survival in
      multivariate analysis (P = 0.001). In the subgroup analysis, elevated CRP was a
      significant prognostic factor in patients with node-positive disease (P = 0.025)
      and was associated with poorer tumor regression (TRG4-5; P = 0.011). CONCLUSIONS:
      The results of our study suggest that preoperative CRP level shows prognostic
      significance in rectal cancer patients that have undergone chemoradiation.
      Therefore, preoperative CRP may help clinicians to identify patients that need
      additional therapy to reduce systemic failure.

PMID- 30288656
TI  - Intercalated discs: cellular adhesion and signaling in heart health and diseases.
AB  - Intercalated discs (ICDs) are highly orchestrated structures that connect
      neighboring cardiomyocytes in the heart. Three major complexes are distinguished
      in ICD: desmosome, adherens junction (AJ), and gap junction (GJ). Desmosomes are
      major cell adhesion junctions that anchor cell membrane to the intermediate
      filament network; AJs connect the actin cytoskeleton of adjacent cells; and gap
      junctions metabolically and electrically connect the cytoplasm of adjacent
      cardiomyocytes. All these complexes work as a single unit, the so-called area
      composita, interdependently rather than individually. Mutation or altered
      expression of ICD proteins results in various cardiac diseases, such as ARVC
      (arrhythmogenic right ventricular cardiomyopathy), dilated cardiomyopathy, and
      hypotrophy cardiomyopathy, eventually leading to heart failure. In this article,
      we first review the recent findings on the structural organization of ICD and
      their functions and then focus on the recent advances in molecular pathogenesis
      of the ICD-related heart diseases, which include two major areas: i) the ICD gene
      mutations in cardiac diseases, and ii) the involvement of ICD proteins in signal
      transduction pathways leading to myocardium remodeling and eventual heart
      failure. These major ICD-related signaling pathways include Wnt/beta-catenin
      pathway, p38 MAPK cascade, Rho-dependent serum response factor (SRF) signaling,
      calcineurin/NFAT signaling, Hippo kinase cascade, etc., which are differentially
      regulated in pathological conditions.

PMID- 30288657
TI  - Genome-wide exploration of C2H2 zinc finger family in durum wheat (Triticum
      turgidum ssp. Durum): insights into the roles in biological processes especially
      stress response.
AB  - C2H2 type of zinc finger transcription factors (C2H2-ZFP TFs) play crucial roles
      in plant developments and stress response. Regarding its importance, genome-wide
      study of C2H2-ZFs were performed in multiple important plant species, but any
      such investigation was not fulfilled in Triticum turgidum ssp. Durum (durum
      wheat) as an important nutritional crop. The present study identified 122 C2H2
      ZFs in durum wheat and physically mapped them onto the genome. The phylogenetic
      analysis classified these TFs into six major groups. Genes structure and
      conserved motifs assay showed TtC2H2-ZF involvement in the important cellular
      functions. Comparative phylogeny between durum wheat TtC2H2-ZF genes and the
      orthologs in rice revealed the evolutionary relationships of C2H2-ZF proteins.
      The gene ontology and promoter cis-element analysis indicated that most of TtC2H2
      ZF genes are involved in multiple molecular functions including metal ion-binding
      and various stimuli responses. Further, the miRNAs targeting TtC2H2-ZF
      transcripts, homology modeling and proteins interaction network were also
      demonstrated, suggesting the vital cellular functions of TtC2H2-ZFs during
      various circumstances. The expression heatmap demonstrated differential and
      tissue-specific expression patterns of these genes. Expression profiling of this
      gene family members in response to dehydration and heat stresses showed
      differential expression pattern of these genes at multiple time points of
      stresses. This study can prepare a comprehensive overview of the durum wheat C2H2
      ZF gene family and may provide a new perspective on the evolution of them, which
      will form the basis for further investigation of the roles of this family members
      and future genetic engineering studies in crops.

PMID- 30288658
TI  - Selenium-Rich Yeast protects against aluminum-induced peroxidation of lipide and
      inflammation in mice liver.
AB  - To investigate the effect of Selenium Rich Yeast (SeY) on hepatotoxicity of
      Aluminium (Al), SeY (0.1 mg/kg) was orally administrated to aluminium-exposed
      mice (10 mg/kg) for 28 days. The risk of oxidative stress was assessed by
      detecting the total antioxidant capacity (T-AOC), catalase activity, H2O2
      content, and mRNA levels of the Keap1/Nrf-2/HO-1 pathway. Inflammatory reactions
      were assessed by detecting the mRNA levels of inflammatory biomarkers. Our
      results showed that SeY protected against the liver histological changes induce
      by Al. The body weight gain of mice treated with SeY + Al restore to normal
      compare with mice exposed to Al alone. Al treatment significantly decreased the
      activities of antioxidant enzymes, reduced T-AOC levels, and up-regulated the
      mRNA level of Nrf2 and HO-1, thereby ultimately leading to peroxidation. SeY
      shown a significant protective effect against oxidative stress caused by Al. In
      addition, Al exposure induced inflammatory responses in rat liver by promoting
      the release of inflammatory cytokines (TNF-a, NF-kB, TNF-R1, IL-1, IL-6, and COX
      2). SeY protected against changes in liver by regulating the mRNA expression
      levels of inflammatory factors. These results suggested that Se protected the
      liver from the Al-induced hepatotoxicity by regulating the mRNA level of
      Keap1/Nrf2/HO-1, and inhibited inflammatory responses by down-regulating the
      expression level of inflammatory cytokine.

PMID- 30288659
TI  - Clinical Significance of the Thioredoxin System and Thioredoxin-Domain-Containing
      Protein Family in Hepatocellular Carcinoma.
AB  - BACKGROUND: Oxidative stress occurs due to the excessive generation of cellular
      reactive oxygen species and antioxidant system dysfunction. The thioredoxin (TXN)
      system and TXN-domain-containing protein (TXNDC) family form networks maintaining
      the cellular reducing environment. Recently, the importance of these genes in the
      tumor environment has been emphasized. AIM: To investigate the clinical
      significance of TXNs and TXNDC family members in HCC. METHODS: Genomic data from
      367 hepatocellular carcinoma (HCC) patients who underwent hepatic resections were
      analyzed to determine genetic alterations in mRNA and protein levels between
      patients and healthy controls. In addition, functional enrichment and survival
      analyses were performed. RESULTS: HCC patients were shown to have enhanced
      expression of TXN, TXNRD1, and TXNDC7/9/14 mRNA and protein compared with
      controls. In accordance with the survival analyses, strong associations were
      found that patients with TXN, TXNRD1, and TXNDC1/7/9 alterations were proven to
      have poor prognosis in overall survival. Moreover, gene set enrichment analysis
      and network analyses revealed that positive correlations were found in mRNA
      expression of TXN, TXNRD1, and TXNDC7/9 genes with upregulation of the tumor
      promoting genes, specifically mTORC1, E2F targets, and Myc targets. On the other
      hand, elevated expressions of TXNIP and TXNDC11 genes were correlated with
      suppression of the above tumor-promoting genes. CONCLUSIONS: TXN system and TXNDC
      family gene panel obtained from the resected tissue of the HCC patients could be
      used to predict survival prognosis of HCC, and these genes could be considered as
      potential therapeutic targets for improving HCC survival.

PMID- 30288660
TI  - Dabigatran Reduces Liver Fibrosis in Thioacetamide-Injured Rats.
AB  - BACKGROUND: Liver fibrosis can progress to cirrhosis, hepatocellular carcinoma,
      or liver failure. Unfortunately, the antifibrotic agents are limited. Thrombin
      activates hepatic stellate cells (HSCs). Therefore, we investigated the effects
      of a direct thrombin inhibitor, dabigatran, on liver fibrosis. METHODS: Adult
      male Sprague-Dawley rats were injected intraperitoneally with thioacetamide (TAA,
      200 mg/kg twice per week) for 8 or 12 weeks to induce liver fibrosis. The injured
      rats were assigned an oral gavage of dabigatran etexilate (30 mg/kg/day) or
      vehicle in the last 4 weeks of TAA administration. Rats receiving an injection of
      normal saline and subsequent oral gavage of dabigatran etexilate or vehicle
      served as controls. RESULTS: In the 8-week TAA-injured rats, dabigatran
      ameliorated fibrosis, fibrin deposition, and phosphorylated ERK1/2 in liver,
      without altering the transcript expression of thrombin receptor protease
      activated receptor-1. In vitro, dabigatran inhibited thrombin-induced HSC
      activation. Furthermore, dabigatran reduced intrahepatic angiogenesis and portal
      hypertension in TAA-injured rats. Similarly, in the 12-week TAA-injured rats, a 4
      week treatment with dabigatran reduced liver fibrosis and portal hypertension.
      CONCLUSIONS: By inhibiting thrombin action, dabigatran reduced liver fibrosis and
      intrahepatic angiogenesis. Dabigatran may be a promising therapeutic agent for
      treatment of liver fibrosis.

PMID- 30288661
TI  - Disparities in Tdap Vaccination and Vaccine Information Needs Among Pregnant
      Women in the United States.
AB  - Objectives The Advisory Committee on Immunization Practices (ACIP) and the
      American College of Obstetricians and Gynecologists (ACOG) recommend that
      pregnant women receive the Tdap vaccine during every pregnancy. The objectives of
      this paper are to evaluate disparities in Tdap vaccination among pregnant women
      in the U.S., and to assess whether race/ethnicity and other characteristics are
      associated with factors that inform pregnant women's decisions about Tdap
      vaccination. Methods We conducted a nationwide cross-sectional web-based survey
      of pregnant women in the U.S. during June-July 2014. The primary outcome was self
      reported vaccination status with Tdap during pregnancy, categorized as
      vaccinated, unvaccinated with intent to be vaccinated during the current
      pregnancy, and unvaccinated with no intent to be vaccinated during the current
      pregnancy. Secondary outcomes included factors that influenced women's decisions
      about vaccination and information needs. We used multivariable logistic
      regression models to estimate odds ratios for associations between race/ethnicity
      and the outcomes. Results Among pregnant women who completed the survey, 41% (95%
      CI 36-45%) reported that they had received Tdap during the current pregnancy.
      Among those women in the third trimester at the time of survey, 52% (95% CI 43
      60%) had received Tdap during the current pregnancy. Hispanic women had higher
      Tdap vaccination than white women and black women (53%, p < 0.05, compared with
      38 and 36%, respectively). In logistic regression models adjusting for maternal
      age, geographic region, education, and income, Hispanic women were more likely to
      have been vaccinated with Tdap compared with white women (aOR 2.29, 95% CI 1.20
      4.37). Higher income and residing in the western U.S. were also independently
      associated with Tdap vaccination during pregnancy. Twenty-six percent of surveyed
      women had not been vaccinated with Tdap yet but intended to receive the vaccine
      during the current pregnancy; this proportion did not differ significantly by
      race/ethnicity. The most common factor that influenced women to get vaccinated
      was a health care provider (HCP) recommendation. The most common reason for not
      getting vaccinated was a concern about safety of the vaccine. Conclusions This
      study found that some disparities exist in Tdap vaccination among pregnant women
      in the U.S., and HCPs have an important role in providing information and
      recommendations about the maternal Tdap recommendation to pregnant women so they
      can make informed vaccination decisions.

PMID- 30288662
TI  - Effectiveness of intraoperative visual evoked potential in avoiding visual
      deterioration during endonasal transsphenoidal surgery for pituitary tumors.
AB  - Postoperative visual function is a major concern in transsphenoidal surgery
      (TSS). Although several reports have demonstrated the importance of visual evoked
      potential (VEP) monitoring during TSS, the usefulness of VEP monitoring have been
      controversial because of its reproducibility. Efficacy of VEP was analyzed in 20
      consecutive cases of patients who underwent endoscopic endonasal TSS surgery. We
      adapted a high-power light-emitting diode stimulator with electroretinography
      using venous anesthesia. In addition, we used black shield patch and braided
      codes to obtain reproducible VEP amplitudes. Stable and reproducible VEP
      waveforms were obtained in 38 of 39 eyes (97.4%) before surgery. Fifteen eyes had
      deteriorated VEP amplitude during operation, and nine eyes had improved VEP
      amplitude at the end of surgery, and six eyes had not improved VEP amplitude. But
      no postoperative visual impairment was observed in all cases by temporary halting
      the surgical manipulation when the VEP was deteriorated. In conclusion, VEP
      monitoring could be a warning sign to avoid postoperative visual dysfunction. We
      recommend VEP as a routine monitoring in TSS.

PMID- 30288663
TI  - The Time Course of Dorsal and Rostral-Ventral Anterior Cingulate Cortex Activity
      in the Emotional Stroop Experiment Reveals Valence and Arousal Aberrant
      Modulation in Patients with Schizophrenia.
AB  - This paper aims to investigate the temporal dynamics within the dorsal anterior
      cingulate cortex (dACC) and the rostral-ventral (rv) ACC during the interaction
      of emotional valence and arousal with cognitive control in patients with
      Schizophrenia (SZ). Although cognitive deficits in SZ are highly relevant and
      emotional disturbances are common, the temporal relationship of brain regions
      involved in the interaction of emotional and cognitive processing in SZ is yet to
      be determined. To address this issue, the reaction time (RT), event-related
      potential (ERP) and temporal dynamics of the dACC and rvACC activity were
      compared between SZ subjects and healthy controls (HC), using a modified
      emotional Stroop experiment (with factors namely congruence, arousal and
      valence). EEG was recorded with 64 channels and source localisation was performed
      using the sLORETA software package. We observed slower initial increase and lower
      peaks of time course activity within the dACC and rvACC in the SZ group. In this
      particular group, the dACC activity during late negativity was negatively
      correlated with a significantly higher RT in the high arousal conflict condition.
      In contrast to HC subjects, at the N450 window, there was no significant valence
      (ERP and rvACC ROI) modulation effect in the SZ subjects. Using high density EEG
      and source localisation, it was possible to distinguish various disturbances
      within the dACC and rvACC in patients with SZ, during emotion-cognition
      processing.

PMID- 30288664
TI  - Does proton pump inhibition change the on-treatment anti-Xa activity in xabans
      treated patients with atrial fibrillation? A pilot study.
AB  - Proton pump inhibition (PPI) reduces gastrointestinal bleeding on direct oral
      anticoagulants. However, PPI may affect dabigatran on-treatment levels; and there
      is no information regarding the effect of PPI on xabans on-treatment activity.
      Thus, the aim of this study was to determine the impact of PPI on therapeutic
      anti-Xa activity in rivaroxaban- and apixaban-treated patients with atrial
      fibrillation (AF). This single-centre pilot prospective study enrolled 77
      consecutive xabans-treated patients (42 rivaroxaban-treated and 35 apixaban
      treated patients) with AF. PPI was administrated in 44 patients. Trough and peak
      anti-Xa activity was assessed with factor Xa-calibrated anti-Xa chromogenic
      analysis. There were no significant differences in trough anti-Xa activity
      comparing PPI-treated patients and patients without PPI (80.5 +/- 66.5 ng/mL in
      PPI group vs. 71.6 +/- 64.1 ng/mL in non-PPI group, p = 0.57, Table 2).
      Similarly, there were no significant differences in peak anti-Xa activity between
      compared groups (175.2 +/- 102.5 ng/mL in PPI group vs. 202.9 +/- 84.1 ng/mL in
      non-PPI group, p = 0.21). This pilot study did not reveal significant changes in
      xabans on-treatment anti-Xa activity according the PPI status.

PMID- 30288665
TI  - Flow convergence visualized in mitral regurgitation with spontaneous echo
      contrast.

PMID- 30288666
TI  - Work disability and its determinants in patients with pituitary tumor-related
      disease.
AB  - INTRODUCTION: Pituitary tumors may have a considerable impact on patients'
      functional status, including paid employment, yet research in this area is
      sparse. OBJECTIVE: To describe work disability and its determinants in patients
      treated for a pituitary tumor. METHODS: Cross-sectional study including patients
      treated for a pituitary tumor in the working age (18-65 years), who completed
      five validated questionnaires assessing work disability [Short Form-Health and
      Labour Questionnaire, Work Role Functioning Questionnaire 2.0 (WRFQ)], health
      related quality of life (HRQoL) and utility (Short Form-36, EuroQoL) and disease
      burden (Leiden Bother and Needs Questionnaire-Pituitary). Additional data were
      extracted from the medical records (age, gender, tumor type, treatment, date of
      diagnosis) and self-reports (marital status, education, endocrine status).
      Associations of disease-specific and sociodemographic characteristics, HRQoL, and
      disease burden with (not) having a paid job were examined through multivariate
      logistic regression. RESULTS: We included 241 patients (61% female, median age 53
      years, median time since diagnosis 11 years), of whom 68 (28%) were without a
      paid job. Patients who had acromegaly, Cushing's disease, (pan)hypopituitarism,
      radiotherapy, were single, less educated, lower HRQoL, and increased disease
      burden were more often without a paid job (p < 0.05). Among those with paid jobs,
      41% reported health-related absenteeism in the previous year. The three work
      incapacitating problems reported by the largest proportion of patients were
      within the mental and social domain (WRFQ). CONCLUSION: Work disability among
      patients treated for a pituitary tumor is substantial. As impact on social
      functioning is high, it is strongly advised to incorporate work disability during
      clinical guidance of patients.

PMID- 30288668
TI  - L-Norvaline Reverses Cognitive Decline and Synaptic Loss in a Murine Model of
      Alzheimer's Disease.
AB  - The urea cycle is strongly implicated in the pathogenesis of Alzheimer's disease
      (AD). Arginase-I (ARGI) accumulation at sites of amyloid-beta (Abeta) deposition
      is associated with L-arginine deprivation and neurodegeneration. An interaction
      between the arginase II (ARGII) and mTOR-ribosomal protein S6 kinase beta-1
      (S6K1) pathways promotes inflammation and oxidative stress. In this study, we
      treated triple-transgenic (3*Tg) mice exhibiting increased S6K1 activity and wild
      type (WT) mice with L-norvaline, which inhibits both arginase and S6K1. The
      acquisition of spatial memory was significantly improved in the treated 3*Tg
      mice, and the improvement was associated with a substantial reduction in
      microgliosis. In these mice, increases in the density of dendritic spines and
      expression levels of neuroplasticity-related proteins were followed by a decline
      in the levels of Abeta toxic oligomeric and fibrillar species in the hippocampus.
      The findings point to an association of local Abeta-driven and immune-mediated
      responses with altered L-arginine metabolism, and they suggest that arginase and
      S6K1 inhibition by L-norvaline may delay the progression of AD.

PMID- 30288669
TI  - Comparison between Enteroscopy-Based and Laparoscopy-Assisted ERCP for Accessing
      the Biliary Tree in Patients with Roux-en-Y Gastric Bypass: Systematic Review and
      Meta-analysis.
AB  - Although balloon-assisted enteroscopy-endoscopic retrograde
      cholangiopancreatography (BAE-ERCP) is a well-described means of accessing the
      duodenal papilla in patients with Roux-en-Y gastric bypass (RYGB), it is
      associated with modest clinical success rates. Laparoscopy-assisted ERCP (LA
      ERCP)-performed by advancing a standard duodenoscope through a gastrostomy into
      the excluded stomach and duodenum-has emerged as a viable alternative to BAE
      ERCP, with apparently higher success rates. In this systematic review, we compare
      LA-ERCP with enteroscopy-based techniques in post-RYGB patients, including 22
      case series that provided data on papilla identification, papilla cannulation,
      and complications. We found that LA-ERCP was superior to the enteroscopy-based
      techniques in its capacity to reach the duodenal papilla, although complication
      rates were lower for the latter. Comparative studies are needed in order to
      corroborate our findings.

PMID- 30288667
TI  - Contributions of TaSUTs to grain weight in wheat under drought.
AB  - KEY MESSAGE: The homologous genes to OsSUT1-5 in wheat were identified and
      detailed analysed. TaSUT1 was the predominant sucrose transporter group and it
      illustrated the genotypic variations towards drought during grain filling.
      Sucrose transporters (SUT) play crucial roles in wheat stem water soluble
      carbohydrate (WSC) remobilization to grain. To determine the major functional SUT
      gene groups in shoot parts of wheat during grain development, drought tolerant
      varieties, Westonia and Kauz, were investigated in field drought experiments.
      Fourteen homologous genes to OsSUT1-5 were identified on five homeologous groups,
      namely TaSUT1_4A, TaSUT1_4B, TaSUT1_4D; TaSUT2_5A, TaSUT2_5B, TaSUT2_5D;
      TaSUT3_1A, TaSUT3_1D; TaSUT4_6A, TaSUT4_6B, TaSUT4_6D; TaSUT5_2A, TaSUT5_2B, and
      TaSUT5_2D, and their gene structures were analysed. Wheat plants above the ground
      were harvested from pre-anthesis to grain maturity and the stem, leaf sheath,
      rachis, lemma and developing grain were used for analysing TaSUT gene expression.
      Grain weight, thousand grain weight, kernel number per spike, biomass and stem
      WSC were characterized. The study showed that among the five TaSUT groups, TaSUT1
      was the predominant sucrose transporting group in all organs sampled, and the
      expression was particularly high in the developing grain. In contrast to TaSUT1,
      the gene expression levels of TaSUT2, TaSUT3 and TaSUT4 were lower, except for
      TaSUT3 which showed preferential expression in the lemma before anthesis. The
      TaSUT5 gene group was very weakly expressed in all tissues. The upregulated gene
      expression of TaSUT1 Westonia type in stem and grain reveal a crucial role in
      stem WSC remobilization to grain under drought. The high TaSUT1 gene expression
      and the significant correlations with thousand grain weight (TGW) and kernel
      number per spike demonstrated the contribution in Kauz's high grain yield in an
      irrigated environment and high TGW in Westonia under drought stress. Further
      molecular level identification is required for gene marker development.

PMID- 30288670
TI  - Is There a Better Design for a Bariatric Procedure? The Case for a Single
      Anastomosis Duodenal Switch.
AB  - The majority of bariatric surgical stapling procedure concepts were developed
      prior to the understanding of obesity as an energy storage disease. Conventional
      treatments did not consider the impact of macronutrients on hormones and glucose
      variability. Current recommendations suggest diets low in glycemic load, with
      moderate protein and unsaturated fat. Roux-en-Y gastric bypass promotes glucose
      variability which can be harmful for health and encourage weight regain. Classic
      duodenal switch with short common channels may prevent absorption of measurable
      fat-soluble vitamins and frequently untested essential fatty acids. The purpose
      of this review is to discuss these factors and explain why single anastomosis
      duodenal switch reduces glucose variability, allows for absorption of critical
      fats and fat-soluble vitamins, and has potential to offer better weight loss and
      metabolic outcomes.

PMID- 30288671
TI  - Order matters: Alphabetizing in-text citations biases citation rates.
AB  - Though citations are critical for communicating science and evaluating scholarly
      success, properties unrelated to the quality of the work-such as cognitive biases
      can influence citation decisions. The primacy effect, in particular, is relevant
      to lists, which for in-text citations could result in citations earlier in the
      list receiving more attention than those later in the list. Therefore, how
      citations are ordered could influence which citations receive the most attention.
      Using a sample of 150,000 articles, we tested whether alphabetizing in-text
      citations biases readers into citing more often articles with first authors whose
      surnames begin with letters early in the alphabet. We found that surnames earlier
      in the alphabet were cited more often than those later in the alphabet when
      journals ordered citations alphabetically compared with chronologically or
      numerically. This effect seemed to be stronger in psychology journals (which have
      a culture of alphabetizing citations) compared with biology or geoscience
      journals (which primarily order chronologically or numerically) and was strongest
      among moderately and highly cited articles. Therefore, alphabetizing in-text
      citations biases citation decisions toward authors with surnames occurring early
      in the alphabet. These citation decisions result from an interaction between
      cognitive biases (more attention devoted to items earlier in a list) and the
      structure of the citation environment (the style in which citations are ordered).
      We suggest that journals using alphabetically ordered citations switch to
      chronological ordering to minimize this arbitrary alphabetical citation bias.

PMID- 30288673
TI  - Activation of peroxymonosulfate by Fe-N complexes embedded within SBA-15 for
      removal of organic contaminants via production of singlet oxygen.
AB  - Persulfates are recognized as promising oxidants and an alternative to Fenton
      reaction for water treatment. However, activation methods in hand restrict the
      practical application. Herein, we explore the possibility of Fe-N complexes being
      a catalyst for persulfate activation for the first time. The catalyst denoted as
      Fe-Im-SBA was synthesized from ferric chloride, imidazole, and SBA-15 at high
      temperature. The internal pore structure of Fe-Im-SBA was maintained well; Fe, N
      and C elements are evenly distributed on the catalyst. This catalyst presents an
      extraordinarily catalytic activity for Rh B removal by PMS activation with a
      removal rate of Rh B that reached up to 97.0% in the first 5 min. It also
      performed well in a wide pH range with complete removal of Rh B in pH ranged from
      0.5 to 10, suggesting the stability of this catalyst in both acidic and alkaline
      conditions. It also showed high adaptability to degrade different kinds of
      pollutants, which could give an attractive advantage of Fe-Im-SBA for
      environmental implications. Through X-ray absorption spectroscopies analysis, it
      shows that the active sites of Fe-Im-SBA are composed of Fe-N4 sites and Fe2-N2
      sites. 1O2 were proved to generate in the Fe-Im-SBA/PMS system and serve as the
      major ROS. Meanwhile, graphitic carbon can accelerate the transfer of electrons,
      which may also be the reason for its high catalytic performance.

PMID- 30288672
TI  - Distribution of organic and inorganic mercury in the tissues and organs of fish
      from the southern Baltic Sea.
AB  - The aim of this study was to determine the distribution of total mercury (THg),
      methylmercury (CH3Hg+), and inorganic mercury (Hginorg) in the tissues and organs
      of fish depending on species, tissue, and organ, and their bioaccumulation in
      tissues and biomagnification throughout the trophic web. The study included four
      species of fish (herring, sprat, cod, and eel) from the southern Baltic Sea. The
      concentrations of the different forms of mercury were determined in tissues and
      internal organs. Intra-specific differences in levels of THg, CH3Hg+, and Hginorg
      in the tissues and organs were determined. Muscle contained the highest
      proportions of THg and CH3Hg+ in comparison to that in the internal organs.
      Differences in concentrations of THg, CH3Hg+, and Hginorg in the tissues and
      organs of fish were related to their preferred prey. The bioaccumulation of
      CH3Hg+ in the tissues and organs of predatory fish at the highest trophic levels
      was greater than in the liver and digestive tract of fish species at lower
      trophic levels, in which Hginorg predominated. The high concentrations of CH3Hg+
      in eel and cod and the low levels in herring and sprat were linked with their
      food and the transfer of this element among species. The results suggested that
      the type of food, feeding habits, and trophic position were important parameters
      that influenced the transfer and biomagnification of mercury in fish.

PMID- 30288674
TI  - Dietary propionic acid enhances antibacterial and immunomodulatory effects of
      oxytetracycline on Nile tilapia, Oreochromis niloticus.
AB  - This study was carried out to evaluate the potential antibacterial and
      immunomodulatory effects of the dietary acidifier propionic acid (PA) when given
      alone or in combination with oxytetracycline (OTC) on Nile tilapia (Oreochromis
      niloticus). Apparently healthy O. niloticus (n = 240; 52 +/- 3.75 g) were
      randomly allocated into four equal groups (n = 60/group): control group fed a
      basal diet alone and the other three groups fed basal diets supplemented with
      either PA (200 mg /kg of diet, PA group) or OTC (500 mg/kg of diet, OTC group)
      alone or in combination (PA + OTC group). Each group was subdivided into two
      subgroups (n = 30/subgroup, each subgroup had triplicate of 10 fish); subgroup
      (A) was used to evaluate the antibacterial effects with the aforementioned 2
      weeks feeding regime, and subgroup (B) was used to evaluate the immunomodulatory
      effects against Aeromonas hydrophila infection with similar 2 weeks feeding
      regime. Among the four groups, PA + OTC group showed the highest significant (p <
      0.0001) antibacterial activity as indicated by widest inhibition zones against A.
      hydrophila and lowest total gastrointestinal bacterial counts. Additionally, this
      group had the best immunomodulatory effect as noticed by a significant (p < 0.05)
      increase in total serum protein, globulin, IgM, phagocytic activity and index,
      lysosome activity, and significant (p < 0.05) upregulation in the expression
      levels of immunity-related genes (MHC I, MHC IIA, MHC IIB, Tlr7, IgM heavy chain,
      TNFalpha, and IL1beta) in head-kidney. Notably, the combined dietary PA and OTC
      improved the hematological parameters and reduced the oxidative damage of
      hepatopancreas and head-kidney induced by OTC. This data suggests dietary PA as
      potential adjuvant to OTC in O. niloticus diets to get maximal antibacterial and
      immunomodulatory effects.

PMID- 30288676
TI  - Abstracts Presented at the Neurocritical Care Society (NCS) 16th Annual Meeting.

PMID- 30288675
TI  - Risk assessment of some organic contaminants: a case study based on food
      consumption in Tanta and Ismailia cities, Egypt.
AB  - The impact of some organic pollutants on some residents of Tanta and Ismailia
      cities of Egypt through their consumption of vegetables, fruits and fish (Nile
      tilapia and catfish) was examined. Residues of organochlorine (OCS) and
      organophosphorus (OPS) as some polychlorinated biphenyls (PCBS) were compared
      with pesticides as well maximum residue limits (MRLS). Probable health risk to
      consumers was also assessed. P, P'-DDT, P, P'-DDE, P, P'-DDD, endrin, alpha-BHC,
      (lindane), and hexachlorbenzene (HCB) were the most detected organochlorine
      compounds, but did not exceed MRLs.However, OPS residues were the most frequently
      detected contaminants. PCBs congeners 28, 70, 52, and 180 were detected in
      tilapia fish from Tanta, but congeners 28 and 180 were the only detected
      congeners in samples collected from Ismailia region. ?PCBS values in all matrices
      did not exceed MRLS. Hazard index (HI) exhibited unity for all compounds at 50
      the decreasing order: catfish > vegetables > fruits > Nile tilapia in Tanta,
      while in Ismailia the order was Nile tilapia > fruit > vegetables. Results also
      revealed that risk values for adults were greater than those of children
      categories.

PMID- 30288677
TI  - Peak Neutrophil-to-Lymphocyte Ratio Correlates with Clinical Outcomes in Patients
      with Severe Traumatic Brain Injury.
AB  - BACKGROUND: Studies suggested that the neutrophil-to-lymphocyte ratio (NLR) was
      associated with unfavorable outcomes in different diseases such as intracerebral
      hemorrhage, cardiovascular problem, cancer, and severe traumatic brain injury
      (sTBI). We aimed to evaluate the relationship between peak NLR and 1-year
      outcomes in patients with sTBI. METHODS: We retrospectively reviewed the clinical
      data of patients with sTBI who were treated in our department between January
      2013 and January 2017. NLRs between day 1 and day 12 after admission as well as
      other related indicators were collected. The relationship between peak NLR and 1
      year outcomes was analyzed. Factors associated with larger peak NLR were also
      explored. RESULTS: A total of 316 patients were included, and 81.3% (257/316)
      experienced unfavorable outcomes. Peak NLR was identified as an independent
      predictor for unfavorable outcomes after sTBI in multivariable logistic
      regression analysis (odds ratio, 1.086; 95% confidence interval, 1.037-1.137; P <
      0.001). Its predictive value was confirmed by receiver operating characteristic
      analysis (area under curve = 0.775; P < 0.001). The day 1 NLR as well as
      admission Glasgow Coma Scale score was independently correlated with increased
      peak NLR. CONCLUSION: Peak NLR was associated with the clinical prognosis after
      sTBI and was a promising predictor for 1-year outcomes.

PMID- 30288679
TI  - Coronary microvascular dysfunction: Filling the research gaps with careful
      patient selection.

PMID- 30288680
TI  - Long-term prognostic value of quantitative myocardial perfusion in patients with
      chest pain and normal coronary arteries.
AB  - BACKGROUND: Patients with chest pain and no obstructive coronary artery disease
      have shown a high incidence of major adverse cardiovascular events (MACE). We
      evaluated the role of absolute myocardial perfusion quantification in predicting
      all-cause mortality and MACE during long-term follow-up in this group of
      patients. METHODS: We studied 79 patients who underwent Nitrogen-13 ammonia PET
      for quantification of global myocardial blood flow (MBF) and myocardial flow
      reserve (MFR) due to suspected impaired myocardial perfusion. Patients with
      coronary artery disease (i.e., > 30% stenosis in one or more coronary arteries)
      were excluded. We assessed all-cause mortality and MACE. MACE was defined as the
      composite incidence of death, myocardial infarction (MI), or hospitalization due
      to heart failure. RESULTS: Median follow-up was 8 (IQR: 3-14) years. Univariate
      Cox regression showed that only MFR (P = 0.01) was a predictor of all-cause
      mortality. Univariate Cox regression analysis showed that both MFR and Stress MBF
      were predictors of the composite endpoint of MACE (P < 0.001 and P = 0.01,
      respectively). CONCLUSION: Quantitative assessment of myocardial perfusion may
      predict all-cause mortality and MACE in patients with chest pain and normal
      coronary arteries in the long-term follow-up.

PMID- 30288678
TI  - Non-granulomatous cerebellar infection by Acanthamoeba spp. in an immunocompetent
      host.
AB  - Acanthamoeba spp. is a free-living amoeba, frequently involved in keratitis by
      contact lens in immunocompetent hosts. Anecdotal reports associate Acanthamoeba
      spp. as a cause of severe granulomatous encephalitis in immunocompromised and,
      less frequently, in immunocompetent subjects. Data regarding clinical and
      therapeutic management are scanty and no defined therapeutic guidelines are
      available. We describe an unusual case of non-granulomatous Acanthamoeba
      cerebellitis in an immunocompetent adult male, with abrupt onset of neurological
      impairment, subtle hemorrhagic infarction at magnetic resonance imaging, and
      initial suspicion of cerebellar neoplasm. Histopathological findings of excised
      cerebellar mass revealed the presence of necrosis and inflammation with structure
      resembling amoebic trophozoites, but without granulomas. Polymerase chain
      reaction from cerebellar tissue was positive for Acanthamoeba T4 genotype. Due to
      gastrointestinal intolerance to miltefosine, the patient was treated with long
      term course of fluconazole and trimethoprim/sulphamethoxazole, obtaining complete
      clinical and neuroradiological resolution.

PMID- 30288681
TI  - Thick and thin: Bridging the gap to a better understanding of apical thinning.

PMID- 30288682
TI  - Safety, Tolerability, and Pharmacokinetics of the Novel Anti-influenza Agent
      Baloxavir Marboxil in Healthy Adults: Phase I Study Findings.
AB  - BACKGROUND AND OBJECTIVE: Baloxavir marboxil, a prodrug that is metabolized to
      baloxavir acid, suppresses viral replication by inhibiting cap-dependent
      endonuclease. This first-in-human phase I study evaluated the safety,
      tolerability, and pharmacokinetics of baloxavir marboxil/baloxavir acid in
      healthy Japanese volunteers (Study 1), while food effects were evaluated in a
      separate phase I, crossover study in healthy Japanese volunteers (Study 2).
      METHODS: Study 1 participants were randomized to single-dose oral baloxavir
      marboxil (6, 20, 40, 60, or 80 mg; n = 6 per dose) or placebo (n = 10), while
      Study 2 participants (n = 15) received single-dose oral baloxavir marboxil 20 mg
      in fasted, fed, and before-meal states. RESULTS: Baloxavir marboxil was well
      tolerated; there were few treatment-emergent adverse events and no serious
      adverse events/deaths. The mean plasma baloxavir acid concentration 24 h after
      single-dose (C24) oral baloxavir marboxil 6 mg was 6.92 ng/mL, exceeding the
      target C24 (6.85 ng/mL) estimated in nonclinical studies. In Study 1, baloxavir
      acid exposure demonstrated dose-proportional increases in the fasted state, with
      maximum plasma concentration generally attained within 3.5 h. Terminal
      elimination half-life ranged from 49 to 91 h. In Study 2, exposure was decreased
      and apparent clearance increased in the fed and before-meal states versus the
      fasted state; however, exposure exceeded the target C24 in all states.
      CONCLUSION: Single-dose oral baloxavir marboxil was well tolerated, had a
      favorable safety profile, and had favorable pharmacokinetic characteristics,
      including a long half-life, supporting single oral dosing. The baloxavir acid
      area under the plasma concentration-time curve decreased with food intake by
      approximately 40%.

PMID- 30288683
TI  - Exploration of Implementation Patterns and Content from a Text-Based Outreach
      Intervention Clinical Trial for Newly Diagnosed, HIV-Positive MSM in Beijing,
      China.
AB  - The Multi-component HIV Intervention Packages for Chinese MSM (China MP3) project
      sought to facilitate engagement in care and initiation of antiretroviral therapy
      among newly HIV-diagnosed men who have sex with men in Beijing, China through the
      implementation of in-person peer-counseling (PC) and a weekly short message
      service (SMS)-based outreach text with as-needed follow-up during the first 12
      months of living with HIV. Implementation of the interactive text-based
      intervention used a 'ticket system' to monitor and document responses to texted
      check-ins and PC follow-up. Using this tracking system, we characterized the 1521
      tickets generated during the China-MP3 intervention across 184 intervention
      participants. A wide variety of topics were the focus of interactions prompted by
      texted outreach although most appeared to focus on issues related to ART and CD4
      and viral load. Almost all participants engaged in at least one SMS-related
      discussion. Sending regular check-ins may offer unique opportunities to newly
      diagnosed MSM to ask questions or gather support between face-to-face visits.

PMID- 30288684
TI  - The Depression Treatment Cascade: Disparities by Alcohol Use, Drug Use, and Panic
      Symptoms Among Patients in Routine HIV Care in the United States.
AB  - Little is known about disparities in depression prevalence, treatment, and
      remission by psychiatric comorbidities and substance use among persons living
      with HIV (PLWH). We conducted a cross-sectional analysis in a large cohort of
      PLWH in routine care and analyzed conditional probabilities of having an
      indication for depression treatment, receiving treatment, receiving indicated
      treatment adjustments, and achieving remission, stratified by alcohol use,
      illicit drug use, and panic symptoms. Overall, 34.7% (95% CI 33.9-35.5%) of
      participants had an indication for depression treatment and of these, 55.3% (53.8
      56.8%) were receiving antidepressants. Among patients receiving antidepressants,
      33.0% (31.1-34.9%) had evidence of remitted depression. In a subsample of sites
      with antidepressant dosage data, only 8.8% (6.7-11.5%) of patients received an
      indicated treatment adjustment. Current drug users (45.8%, 95% CI 43.6-48.1%) and
      patients reporting full symptoms of panic disorder (75.0%, 95% CI 72.9-77.1%)
      were most likely to have an indication for antidepressant treatment, least likely
      to receive treatment given an indication (current drug use: 47.6%, 95% CI 44.3
      51.0%; full panic symptoms: 50.8%, 95% CI 48.0-53.6%), or have evidence of
      remitted depression when treated (22.3%, 95% CI 18.5-26.6%; and 7.3%, 95% CI 5.5
      9.6%, respectively). In a multivariable model, drug use and panic symptoms were
      independently associated with poorer outcomes along the depression treatment
      cascade. Few differences were evident by alcohol use. Current drug users were
      most likely to have an indication for depression treatment, but were least likely
      to be receiving treatment or to have remitted depression. These same disparities
      were even more starkly evident among patients with co-occurring symptoms of panic
      disorder compared to those without. Achieving improvements in the depression
      treatment cascade will likely require attention to substance use and psychiatric
      comorbidities.

PMID- 30288685
TI  - Real-World Results of Switching Treatment from Ranibizumab to Aflibercept in
      Macular Oedema Secondary to Branch Retinal Vein Occlusion.
AB  - INTRODUCTION: To investigate treatment outcomes after switching from ranibizumab
      to aflibercept intravitreal injections in patients with macular oedema (MO)
      secondary to branch retinal vein occlusion (BRVO). METHODS: Eligible patients
      with refractory MO secondary to BRVO, post treatment with a minimum of three
      intravitreal injections of ranibizumab at 4-weekly intervals were recruited.
      Suboptimal or non-responders were defined as patients who had persistent
      intraretinal fluid (< 75% decrease from baseline) despite a minimum of three
      consecutive injections. These patients were switched to aflibercept injections on
      an as-needed basis. The primary study outcomes assessed trends in best-corrected
      distance visual acuity (BCVA) and central retinal thickness (CRT). To compare
      means of BCVA and CRT, a paired t test two-tailed with a level of significance
      set at 0.05 was used. Pearson correlation coefficient was also applied to
      demonstrate correlation. Participants were followed up for a period of 24 weeks
      after switching. RESULTS: Thirty-eight eyes of 38 patients were included in the
      study. Patients had an average of 8.37 ranibizumab intravitreal injections over a
      mean period of 12 months presenting suboptimal or no response. A significant
      decrease of mean CRT from 388.63 +/- 93.4 MUm to 290.29 +/- 93.5 MUm (p < 0.001)
      and an improvement in mean BCVA from logMAR 0.66 +/- 0.38 to logMAR 0.57 +/- 0.27
      (p = 0.025) was achieved after an average of 2.27 aflibercept injections.
      CONCLUSIONS: Given the spectrum of therapies available to date for the management
      of MO secondary to BRVO, aflibercept appears to be an effective treatment option
      in cases refractory to ranibizumab. This study based on a small cohort of
      patients indicates that satisfactory results on retinal anatomy and visual
      outcomes can be accomplished with a smaller number of injections. Larger-scale
      studies are needed to extrapolate these promising results.

PMID- 30288686
TI  - One mirror effect: The regularities of recognition memory.
AB  - The mirror effect is a pattern of results generally found in two-condition
      recognition memory experiments that is consistent with normative signal detection
      theory as a model of recognition. However, the claim has been made that there is
      a distinct mirror effect, the "strength mirror effect," that differs from the
      normative one. This claim is based on experiments on recognition memory in which
      repetition or study time is varied to produce differences in accuracy, where
      typically the ordinary mirror effect pattern is absent. If this claim is correct,
      it has major implications for theories of recognition memory. Therefore, a full
      examination of the data that support the claim was called for. To do that, we
      replicated the basic demonstration of the no-mirror-effect data and analyzed it
      further in a series of experiments. The analysis showed the following: (1)
      Whether or not the mirror effect occurs is determined by whether the experimenter
      furnishes effective discriminanda that distinguish the weak and strong conditions
      for the participant. (2) Once Finding 1 is taken into account, no adjustments of
      or additions to the normative signal detection theory explanations are necessary.
      (3) There is only one mirror effect, and no separate "strength mirror effect."

PMID- 30288687
TI  - Inhibitors Compounds on Sugarcane Bagasse Saccharification: Effects of
      Pretreatment Methods and Alternatives to Decrease Inhibition.
AB  - Considering bioethanol production, extensive research has been performed to
      decrease inhibitors produced during pretreatments, to diminish energy input, and
      to decrease costs. In this study, sugarcane bagasse was pretreated with NaOH,
      H2SO4, and water. The higher concentration of phenols, 3.3 g/L, was observed in
      biomass liquid fraction after alkaline pretreatment. Acid pretreatment was
      responsible to release considerable acetic acid concentration, 2.3 g/L, while
      water-based pretreatment was the only to release formic acid, 0.02 g/L. Furans
      derivatives were not detected in liquid fractions regardless of pretreatment.
      Furthermore, washing step removed most of the phenols from pretreated sugarcane
      bagasse. Saccharification of alkali-pretreated biomass plus polyethylene glycol
      (PEG) at 0.4% (w/v) enhanced 8 and 26% the glucose and the xylose release,
      respectively, while polyvinylpyrrolidone (PVP) also at 0.4% (w/v) increased the
      release by 10 and 31% of these sugars, respectively, even without washing and
      filtration steps. Moreover, these polymers cause above 50% activation of
      endoglucanase and xylanase activities which are crucial for biomass hydrolysis.

PMID- 30288688
TI  - Association of CILP, COL9A2 and MMP3 Gene Polymorphisms with Lumbar Disc
      Degeneration in an Indian Population.
AB  - Lumbar disc degeneration (LDD) is a multifactorial disorder caused by genetic and
      environmental factors. Polymorphisms in several structural and inflammatory genes
      like collagens, aggrecan, matrix metalloproteinases are associated with the risk
      of disc degeneration. In this study, we analyzed the role of a few important
      single nucleotide polymorphisms in cartilage intermediate layer protein (CILP),
      collagen 9A2 (COL9A2) and matrix metalloproteinase 3 (MMP3) genes in LDD from an
      Indian population. Two hundred patients with LDD and 200 healthy controls were
      recruited for the study. Genotyping was performed by allelic discrimination
      assay. The rs2073711 polymorphism (CILP gene - GG genotype) was associated with
      reduced risk of LDD in the Indian population (OR = 0.43, p = 0.016). The rs591058
      polymorphism (MMP3 gene - TT genotype) is found to be associated with lower risk
      among women (OR = 0.34, p = 0.041). No significant association was found between
      COL9A2 polymorphism rs7533552 and the risk of LDD. We conclude that the CILP gene
      polymorphism (rs2073711) is associated with a lower risk of LDD, the MMP3
      (rs591058) gene polymorphism is associated with LDD among women, and the TT
      genotype confers a lower risk of LDD.

PMID- 30288690
TI  - Feature-based attention across saccades: Pop-out in color search is spatiotopic.
AB  - Our perception of the world remains stable despite the retinal shifts that occur
      with each saccade. The role of spatial attention in matching pre- to postsaccadic
      visual information has been well established, but the role of feature-based
      attention remains unclear. In this study, we examined the transsaccadic
      processing of a color pop-out target. Participants made a saccade towards a
      neutral target and performed a search task on a peripheral array presented once
      the saccade landed. A similar array was presented just before the saccade and we
      analyzed what aspect of this preview benefitted the postsaccadic search task. We
      assessed the preview effect in the spatiotopic and retinotopic reference frames,
      and the potential transfer of feature selectivity across the saccade. In the
      first experiment, the target and distractor colors remained identical for the
      preview and the postsaccadic array and performance improved. The largest benefit
      was observed at the spatiotopic location. In the second experiment, the target
      and distractor colors were swapped across the saccade. All responses were slowed
      but the cost was least at the spatiotopic location. Our results show that the
      preview attracted spatial attention to the target location, which was then
      remapped, and suggest that previewed features, specifically colors, were
      transferred across the saccade. Furthermore, the preview induced a spatiotopic
      advantage regardless of whether the target switched color or not, suggesting that
      spatiotopy was established independently of feature processing. Our results
      support independent priming effects of features versus location and underline the
      role of feature-based selection in visual stability.

PMID- 30288689
TI  - Agaricus bisporus supplementation reduces high-fat diet-induced body weight gain
      and fatty liver development.
AB  - Obesity is a global epidemic characterized not only by excessive fat deposition
      but also by important complications such as nonalcoholic liver steatosis.
      Beneficial antiobesogenic effects have been described for some mushrooms. The
      current study aimed to demonstrate the protective effect of Agaricus bisporus
      (AB) supplementation against the metabolic alterations induced by high-fat-diet
      (HFD) feeding. Eight-week-old C57BL/6J mice were fed for 10 weeks with one of the
      following diets: (1) control diet (n = 7), (2) HFD (n = 7), (3) HFD supplemented
      with 5% AB (n = 9), and (4) HFD supplemented with 10% AB (n = 9). A pair-fed
      group was also included for the 10% AB group (n = 6). The impact of AB
      supplementation on food intake, body weight gain, and liver and fat pad weights
      was examined. Biochemical, histological, and molecular parameters were also
      analyzed. Dietary supplementation with 10% AB reduced the HFD-induced increase in
      body, epididymal, and mesenteric fat weights (p < 0.01, p < 0.05, and p < 0.05,
      respectively). Supplementation with AB also reduced liver damage in a dose
      dependent manner (p < 0.01 and p < 0.001). This effect was confirmed by
      histological analysis that showed that liver steatosis was markedly reduced in
      mice fed with AB. The beneficial properties of 10% AB supplementation appear to
      be mediated through a decrease in food intake and via stimulation of mesenteric
      and hepatic free-fatty acid beta-oxidation, along with a decrease in epidydimal
      and hepatic expression of CD36. In conclusion, supplementation with AB prevents
      excessive body weight gain and liver steatosis induced by HFD consumption.

PMID- 30288691
TI  - Surgical Management of Gastroesophageal Reflux Disease in Patients with Severe
      Esophageal Dysmotility.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) and esophageal dysmotility are
      often disqualifying criteria for fundoplication due to dysphagia complications. A
      tailored partial fundoplication may improve GERD in patients with severe
      esophageal motility disorders. We evaluate this approach on GERD improvement in
      non-achalasia esophageal dysmotility patients. METHODS: A single-institution
      prospective database was reviewed (2007-2016), with inclusion criteria of GERD,
      previous diagnosis of non-achalasia esophageal motility disorder, and
      laparoscopic partial fundoplication. Diagnosis of previous achalasia diagnosis or
      diffused esophageal spasm was excluded. Motility studies, pre- and post-upper
      gastrointestinal imaging (UGI), esophageal symptom scores, antacid, and PPI use
      were collected pre-op, 6 months, 12 months, and long-term (LT). Statistical
      analysis was made using SPSS v.23.0.0, alpha = 0.05. RESULTS: Fifty-two patients
      met the inclusion criteria. A total of 17.3% had esophageal body amotility, 79.6%
      had severe esophageal dysmotility. A total of 65.9% women (mean age 64 +/- 15.7),
      mean peristalsis 45.3 +/- 32.6%, and failed peristalsis 36.0 +/- 32.2%. Mean LES
      residual pressure was 15.0 +/- 18.0 mmHg, and 40.7% had hypotensive LES. Mean
      follow-up time was 25 months [1-7 years], with significant improvement in
      symptoms and reduction in PPI and antacid use at all time-points compared to pre
      op. A total of 74% had UGI studies at 12 months; all showed persistent
      dysmotility. Six patients had radiographic hiatal hernia recurrence, with only
      one being clinically symptomatic postoperatively. Three required dilation for
      persistent dysphagia. CONCLUSIONS: A tailored partial fundoplication may be
      effective in symptom relief for non-achalasia patients with esophageal motility
      disorders and GERD. Significant symptom improvement, low HHR, and PPI use clearly
      indicate this approach to be effective for this population.

PMID- 30288692
TI  - Abdominal Aortic Aneurysm Volumetric Evaluation During Mid-term Follow-Up After
      Endovascular Sealing Using the NellixTM Device.
AB  - OBJECTIVES: To analyze the volumetric evolution of abdominal aortic aneurysms
      after endovascular sealing (EVAS) with the NellixTM device during follow-up.
      METHODS: Patients who underwent elective EVAS in our institution in 2014 and 2015
      were retrospectively reviewed. Preoperative, postoperative and 1-year scans were
      processed. A custom software was conceived to assess semi-automated measurements
      of the aneurysm sac and the endograft sizes including volume, maximum diameter,
      sectional area and perimeter. Thrombus volume, aneurysm length, mean distance
      between the stents inside the polymer-filled sacs and endograft migration were
      also estimated. Manual maximum diameters were measured for comparison. Inter and
      intra-observer variability of the proposed semi-automated method was evaluated.
      RESULTS: Pre-EVAS, post-EVAS and last follow-up scans of 12 patients were finally
      analyzed during a mean follow-up of 17 +/- 5 months. No endograft migration or
      endoleak were detected. During follow-up, aneurysm volume and perimeter slightly
      increased compared to post-EVAS scans (+ 1 and + 5%, respectively, p < 0.05). A
      systematic 6% enlargement of the endobag volume was also observed (range 1-15 mL,
      p < 0.001). Endobag maximum diameter, area and perimeter increased 4, 8, and 8%,
      respectively (all p < 0.01). Mean plane-by-plane distance between stents
      increased 4% (p < 0.05). Mean thrombus volume did not change during follow-up,
      although a high variability was observed. Aneurysm and thrombus volume changes
      were highly correlated (r = 0.93, p < 0.001). No associations were observed
      between aneurysm and endobag volume changes. Intra- and inter-observer
      variability was below 1.7 and 2.4% for diameter and volume measurements,
      respectively. The automated measurements of post-EVAS aneurysm diameter and
      volume were higher than preoperative (p < 0.05). Maximum diameters measured
      manually did not differ between scans. CONCLUSION: Small aneurysm volume
      enlargement detected during a mid-term follow-up was associated with thrombus
      size change, whereas systematic endograft expansion resulted independent from the
      aortic growth. Volumetric measurements using a semi-automated method could
      quantify small changes in aneurysm, endograft and thrombus sizes not detected by
      manually defined maximal diameters.

PMID- 30288693
TI  - Early ileostomy reversal after minimally invasive surgery and ERAS program for
      mid and low rectal cancer.
AB  - Diverting loop ileostomy following low anterior resection (LAR) is known to
      decrease quality of life and prolongs the return back to patients' baseline
      activity. The aim of this retrospective study was to explore feasibility and
      safety of an early ileostomy reversal strategy in a cohort of patients undergoing
      minimally invasive LAR within an enhanced recovery after surgery (ERAS) program.
      Prospectively collected data from 15 patients who underwent minimally invasive
      LAR and diverting ileostomy at the Division of General and Hepatobiliary Surgery,
      University of Verona Hospital Trust between September 2015 and December 2016 were
      retrospectively analyzed. Of 15 patients, 10 patients underwent laparoscopic LAR
      and 5 patients a robot-assisted procedure. Post-operative complications were
      observed in 5 patients. Four patients suffered Clavien-Dindo grade 1 or 2
      complications, and one patient required redo surgery due to bowel obstruction at
      the ileostomy site (grade 3b). Following ileostomy reversal, 10 out of 15
      patients experienced complications. Two patients required redo surgery for bowel
      obstruction (grade 3b), whilst eight patients suffered grade 1 or 2
      complications, being surgical site infection the most frequently observed (6
      cases). Despite that, 80% of patients had their ileostomy reversed within 30 days
      and median time from initial surgery to ileostomy reversal was 22 days (range 10
      150). Early ileostomy closure after minimally invasive LAR and ERAS program is
      feasible although it carries non-negligible risk of severe complications which,
      however, does not hinder its accomplishment.

PMID- 30288694
TI  - Neuron-Type Specific Loss of CDKL5 Leads to Alterations in mTOR Signaling and
      Synaptic Markers.
AB  - CDKL5 disorder is a devastating neurodevelopmental disorder associated with
      epilepsy, developmental retardation, autism, and related phenotypes. Mutations in
      the CDKL5 gene, encoding CDKL5, have been identified in this disorder. CDKL5 is a
      protein with homology to the serine-threonine kinases and incompletely
      characterized function. We generated and validated a murine model bearing a
      floxed allele of CDKL5 and polyclonal antibodies to CDKL5. CDKL5 is well
      expressed in the cortex, hippocampus, and striatum, localized to synaptosomes and
      nuclei and developmentally regulated in the hippocampus. Using Cre-mediated
      mechanisms, we deleted CDKL5 from excitatory CaMKIIalpha-positive neurons or
      inhibitory GABAergic neurons. Our data indicate that loss of CDKL5 in excitatory
      neurons of the cortex or inhibitory neurons of the striatum differentially alters
      expression of some components of the mechanistic target of rapamycin (mTOR)
      signaling pathway. Further loss of CDKL5 in excitatory neurons of the cortex or
      inhibitory neurons of the striatum leads to alterations in levels of synaptic
      markers in a neuron-type specific manner. Taken together, these data support a
      model in which loss of CDKL5 alters mTOR signaling and synaptic compositions in a
      neuron-type specific manner and suggest that CDKL5 may have distinct functional
      roles related to cellular signaling in excitatory and inhibitory neurons. Thus,
      these studies provide new insights into the biology of CDKL5 and suggest that the
      molecular pathology in CDKL5 disorder may have distinct neuron-type specific
      origins and effects.

PMID- 30288695
TI  - Cortical Excitability and Activation of TrkB Signaling During Rebound Slow
      Oscillations Are Critical for Rapid Antidepressant Responses.
AB  - Rapid antidepressant effects of ketamine become most evident when its
      psychotomimetic effects subside, but the neurobiological basis of this "lag"
      remains unclear. Laughing gas (N2O), another NMDA-R (N-methyl-D-aspartate
      receptor) blocker, has been reported to bring antidepressant effects rapidly upon
      drug discontinuation. We took advantage of the exceptional pharmacokinetic
      properties of N2O to investigate EEG (electroencephalogram) alterations and
      molecular determinants of antidepressant actions during and immediately after
      NMDA-R blockade. Effects of the drugs on brain activity were investigated in
      C57BL/6 mice using quantitative EEG recordings. Western blot and qPCR were used
      for molecular analyses. Learned helplessness (LH) was used to assess
      antidepressant-like behavior. Immediate-early genes (e.g., bdnf) and
      phosphorylation of mitogen-activated protein kinase-markers of neuronal
      excitability-were upregulated during N2O exposure. Notably, phosphorylation of
      BDNF receptor TrkB and GSK3beta (glycogen synthase kinase 3beta) became regulated
      only gradually upon N2O discontinuation, during a brain state dominated by slow
      EEG activity. Subanesthetic ketamine and flurothyl-induced convulsions
      (reminiscent of electroconvulsive therapy) also evoked slow oscillations when
      their acute pharmacological effects subsided. The correlation between ongoing
      slow EEG oscillations and TrkB-GSK3beta signaling was further strengthened
      utilizing medetomidine, a hypnotic-sedative agent that facilitates slow
      oscillations directly through the activation of alpha2-adrenergic autoreceptors.
      Medetomidine did not, however, facilitate markers of neuronal excitability or
      produce antidepressant-like behavioral changes in LH. Our results support a
      hypothesis that transient cortical excitability and the subsequent regulation of
      TrkB and GSK3beta signaling during homeostatic emergence of slow oscillations are
      critical components for rapid antidepressant responses.

PMID- 30288696
TI  - Early Manifestations of Brain Aging in Mice Due to Low Dietary Folate and Mild
      MTHFR Deficiency.
AB  - Folate is an important B vitamin required for methylation reactions, nucleotide
      and neurotransmitter synthesis, and maintenance of homocysteine at nontoxic
      levels. Its metabolism is tightly linked to that of choline, a precursor to
      acetylcholine and membrane phospholipids. Low folate intake and genetic variants
      in folate metabolism, such as the methylenetetrahydrofolate reductase (MTHFR) 677
      C>T polymorphism, have been suggested to impact brain function and increase the
      risk for cognitive decline and late-onset Alzheimer's disease. Our study aimed to
      assess the impact of genetic and nutritional disturbances in folate metabolism,
      and their potential interaction, on features of cognitive decline and brain
      biochemistry in a mouse model. Wild-type and Mthfr+/- mice, a model for the MTHFR
      677 C>T polymorphism, were fed control or folate-deficient diets from weaning
      until 8 and 10 months of age. We observed short-term memory impairment measured
      by the novel object paradigm, altered transcriptional levels of synaptic markers
      and epigenetic enzymes, as well as impaired choline metabolism due to the Mthfr+/
      genotype in cortex or hippocampus. We also detected changes in mRNA levels of
      Presenillin-1, neurotrophic factors, one-carbon metabolic and epigenetic enzymes,
      as well as reduced levels of S-adenosylmethionine and acetylcholine, due to the
      folate-deficient diet. These findings shed further insights into the mechanisms
      by which genetic and dietary folate metabolic disturbances increase the risk for
      cognitive decline and suggest that these mechanisms are distinct.

PMID- 30288697
TI  - Inhibition of Autophagy by Captopril Attenuates Prion Peptide-Mediated Neuronal
      Apoptosis via AMPK Activation.
AB  - Accumulation of prion protein (PrPc) into a protease-resistant form (PrPsc) in
      the brains of humans and animals affects the central nervous system. PrPsc occurs
      only in mammals with transmissible prion diseases. Prion protein refers to either
      the infectious pathogen itself or the main component of the pathogen. Recent
      studies suggest that autophagy is one of the major functions that keep cells
      alive and which has a protective effect against neurodegeneration. In this study,
      we investigated whether the anti-hypertensive drug, captopril, could attenuate
      prion peptide PrP (106-126)-induced calcium alteration-mediated neurotoxicity.
      Treatment with captopril increased both LC3-II (microtubule-associated protein
      1A/1B-light chain 3-II) and p62 protein levels, indicating autophagy flux
      inhibition. Electron microscopy confirmed the occurrence of autophagic flux
      inhibition in neuronal cells treated with captopril. Captopril attenuated PrP
      (106-126)-induced neuronal cell death via AMPK activation and autophagy
      inhibition. Compound C suppressed AMPK activation as well as the neuroprotective
      effects of captopril. Thus, these data showed that an anti-hypertensive drug has
      a protective effect against prion-mediated neuronal cell death via autophagy
      inhibition and AMPK activation, and also suggest that anti-hypertensive drugs may
      be effective therapeutic agents against neurodegenerative disorders, including
      prion diseases.

PMID- 30288698
TI  - A robust method for segmenting pectoral muscle in mediolateral oblique (MLO)
      mammograms.
AB  - PURPOSE: Accurately detecting and removing pectoral muscle areas depicting on
      mediolateral oblique (MLO) view mammograms are an important step to develop a
      computer-aided detection scheme to assess global mammographic density or tissue
      patterns. This study aims to develop and test a new fully automated, accurate and
      robust method for segmenting pectoral muscle in MLO mammograms. METHODS: The new
      method includes the following steps. First, a small rectangular region in the top
      left corner of the MLO mammogram which may contain pectoral muscle is captured
      and enhanced by the fractional differential method. Next, an improved iterative
      threshold method is applied to segment a rough binary boundary of the pectoral
      muscle in the small region. Then, a rough contour is fitted with the least
      squares method on the basis of points of the rough boundary. Last, the fitting
      contour is subjected to local active contour evolution to obtain the final
      pectoral muscle segmentation line. The method has been tested on 720 MLO
      mammograms. RESULTS: The segmentation results generated using the new scheme were
      evaluated by two expert mammographic radiologists using a 5-scale rating system.
      More than 65% were rated above scale 3. When assessing the segmentation results
      generated using Hough transform, morphologic thresholding methods and Unet-based
      model, less than 20%, 35% and 47% of segmentation results were rated above scale
      3 by two radiologists, respectively. Quantitative data analysis results show that
      the Dice coefficient of 0.986 +/- 0.005 is obtained. In addition, the mean rate
      of errors and Hausdorff distance between the contours detected by automated and
      manual segmentation are FP = 1.71 +/- 3.82%, FN = 5.20 +/- 3.94% and 2.75 +/-
      1.39 mm separately. CONCLUSION: The proposed method can be used to segment the
      pectoral muscle in MLO mammograms with higher accuracy and robustness.

PMID- 30288699
TI  - Conditions for reliable grip force and jaw angle estimation of da Vinci surgical
      tools.
AB  - PURPOSE: This work presents an estimation technique as well as corresponding
      conditions which are necessary to produce an accurate estimate of grip force and
      jaw angle on a da Vinci surgical tool using back-end sensors alone. METHODS: This
      work utilizes an artificial neural network as the regression estimator on a
      dataset acquired from custom hardware on the proximal and distal ends. Through a
      series of experiments, we test the effect of estimation accuracy due to change in
      operating frequency, using the opposite jaw, and using different tools. A case
      study is then presented comparing our estimation technique with direct
      measurements of material response curves on two synthetic tissue surrogates.
      RESULTS: We establish the following criteria as necessary to produce an accurate
      estimate: operate within training frequency bounds, use the same side jaw, and
      use the same tool. Under these criteria, an average root mean square error of
      1.04 mN m in grip force and 0.17 degrees in jaw angle is achieved. Additionally,
      applying these criteria in the case study resulted in direct measurements which
      fell within the 95% confidence bands of our estimation technique. CONCLUSION: Our
      estimation technique, along with important training criteria, is presented herein
      to further improve the literature pertaining to grip force estimation. We propose
      the training criteria to begin establishing bounds on the applicability of
      estimation techniques used for grip force estimation for eventual translation
      into clinical practice.

PMID- 30288700
TI  - Intravitreal Ranibizumab Therapy for Diabetic Macular Edema in Routine Practice:
      Two-Year Real-Life Data from a Non-interventional, Multicenter Study in Germany.
AB  - INTRODUCTION: The prospective, non-interventional OCEAN study examined the use of
      intravitreal ranibizumab injections for the treatment of diabetic macular oedema
      (DME) in a real-world setting in Germany. METHODS: Adults with DME receiving >= 1
      ranibizumab (0.5 mg) injections were recruited by 250 ophthalmologists. Best
      corrected visual acuity (VA) testing, imaging and treatments were performed
      according to the investigators' routine practice and documented over 24 months.
      RESULTS: The full analysis set included 1226 participants. Mean baseline VA was
      60.6 [95% CI: 59.7; 61.5] Early Treatment Diabetic Retinopathy Study letters. VA
      improved by >= 15 letters in 21.5% and 23.5% of the participants at 12 months and
      24 months, respectively. They received a mean number of 4.42 [95% CI: 4.30; 4.54]
      injections in the first year and 5.52 [95% CI: 5.32; 5.73] injections over 24
      months, which was markedly lower than in clinical trials. Only 33.4% of the
      participants received an upload with four initial monthly injections as
      recommended by the German ophthalmologic societies. Time-to-event analyses that
      account for missing data inherent to a non-interventional study design
      demonstrated that participants receiving >= 7 injections in the first year had a
      faster response, but the duration of the response was shorter compared to the
      subgroups receiving 1-3 and 4-6 injections. Serious adverse events were reported
      for 143/1250 (11.4%) participants in the safety population. CONCLUSION: Under
      treatment is a major problem of DME anti- vascular endothelial growth factor
      therapy under real life conditions. Despite fewer injections given compared to
      randomised controlled trials with a consequently reduced overall mean visual
      gain, a profound functional improvement (>= 15 letters) was achieved over 2 years
      in 23.5% of eyes with DME. TRIAL REGISTRATION NUMBER: NCT02194803,
      ClinicalTrials.gov. FUNDING: Novartis Pharma GmbH, Nuremberg, Germany.

PMID- 30288701
TI  - Gene Regulatory Networks Mediating Cold Acclimation: The CBF Pathway.
AB  - Under low nonfreezing temperature conditions, plants from temperate climates
      undergo physiological and biochemical adjustments that increase their tolerance
      to freezing temperatures. This response, termed cold acclimation, is largely
      regulated by changes in gene expression. Molecular and genetic studies have
      identified a small family of transcription factors, called C-repeat binding
      factors (CBFs), as key regulators of the transcriptomic rearrangement that leads
      to cold acclimation. The function of these proteins is tightly controlled, and an
      inadequate supply of CBF activity may be detrimental to the plant. Accumulated
      evidence has revealed an extremely intricate network of positive and negative
      regulators of cold acclimation that coalesce at the level of CBF promoters
      constituting a central hub where multiple internal and external signals are
      integrated. Moreover, CBF expression is also controlled at posttranscriptional
      and posttranslational levels further refining CBF regulation. Recently, natural
      variation studies in Arabidopsis have demonstrated that mutations resulting in
      changes in CBF expression have an adaptive value for wild populations.
      Intriguingly, CBF genes are also present in plant species that do not cold
      acclimate, which suggest that they may also have additional functions. For
      instance, CBFs are required for some cold-related abiotic stress responses. In
      addition, their involvement in plant development deserves further study. Although
      more studies are necessary to fully harness CBF biotechnological potential, these
      transcription factors are meant to be key for a rational design of crops with
      enhanced tolerance to abiotic stress.

PMID- 30288702
TI  - RNA Regulation in Plant Cold Stress Response.
AB  - In addition to plants, all organisms react to environmental stimuli via the
      perception of signals and subsequently respond through alterations of gene
      expression. However, genes/mRNAs are usually not the functional unit themselves,
      and instead, resultant protein products with individual functions result in
      various acquired phenotypes. In order to fully characterize the adaptive
      responses of plants to environmental stimuli, it is essential to determine the
      level of proteins, in addition to the regulation of mRNA expression. This
      regulatory step, which is referred to as "mRNA posttranscriptional regulation,"
      occurs subsequent to mRNA transcription and prior to translation. Although these
      RNA regulatory mechanisms have been well-studied in many organisms, including
      plants, it is not fully understood how plants respond to environmental stimuli,
      such as cold stress, via these RNA regulations.A recent study described several
      RNA regulatory factors in relation to environmental stress responses, including
      plant cold stress tolerance. In this chapter, the functions of RNA regulatory
      factors and comprehensive analyses related to the RNA regulations involved in
      cold stress response are summarized, such as mRNA maturation, including capping,
      splicing, polyadenylation of mRNA, and the quality control system of mRNA; mRNA
      degradation, including the decapping step; and mRNA stabilization. In addition,
      the putative roles of messenger ribonucleoprotein (mRNP) granules, such as
      processing bodies (PBs) and stress granules (SGs), which are cytoplasmic
      particles, are described in relation to RNA regulations under stress conditions.
      These RNA regulatory systems are important for adjusting or fine-tuning and
      determining the final levels of mRNAs and proteins in order to adapt or respond
      to environmental stresses. Collectively, these new areas of study revealed that
      plants possess precise novel regulatory mechanisms which specifically function in
      the response to cold stress.

PMID- 30288703
TI  - The Mechanism Enabling Hibernation in Mammals.
AB  - Some rodents including squirrels and hamsters undergo hibernation. During
      hibernation, body temperature drops to only a few degrees above ambient
      temperature. The suppression of whole-body energy expenditure is associated with
      regulated, but not passive, reduction of cellular metabolism. The heart retains
      the ability to beat constantly, although body temperature drops to less than 10 
      degrees C during hibernation. Cardiac myocytes of hibernating mammals are
      characterized by reduced Ca2+ entry into the cell membrane and a concomitant
      enhancement of Ca2+ release from and reuptake by the sarcoplasmic reticulum.
      These adaptive changes would help in preventing excessive Ca2+ entry and its
      overload and in maintaining the resting levels of intracellular Ca2+. Adaptive
      changes in gene expression in the heart prior to hibernation may be indispensable
      for acquiring cold resistance. In addition, protective effects of cold-shock
      proteins are thought to have an important role. We recently reported the unique
      expression pattern of cold-inducible RNA-binding protein (CIRP) in the hearts of
      hibernating hamsters. The CIRP mRNA is constitutively expressed in the heart of a
      nonhibernating euthermic hamster with several different forms probably due to
      alternative splicing. The short product contained the complete open reading frame
      for full-length CIRP, while the long product had inserted sequences containing a
      stop codon, suggesting production of a C-terminal deletion isoform of CIRP. In
      contrast to nonhibernating hamsters, only the short product was found in
      hibernating animals. Thus, these results indicate that CIRP expression in the
      hamster heart is regulated at the level of alternative splicing, which would
      permit a rapid increment of functional CIRP when entering hibernation. We will
      summarize the current understanding of the cold-resistant property of the heart
      in hibernating animals.

PMID- 30288704
TI  - Freezing Tolerance of Plant Cells: From the Aspect of Plasma Membrane and
      Microdomain.
AB  - Freezing stress is accompanied by a state change from water to ice and has
      multiple facets causing dehydration; consequently, hyperosmotic and mechanical
      stresses coupled with unfavorable chilling stress act in a parallel way. Freezing
      tolerance varies widely among plant species, and, for example, most temperate
      plants can overcome deleterious effects caused by freezing temperatures in
      winter. Destabilization and dysfunction of the plasma membrane are tightly linked
      to freezing injury of plant cells. Plant freezing tolerance increases upon
      exposure to nonfreezing low temperatures (cold acclimation). Recent studies have
      unveiled pleiotropic responses of plasma membrane lipids and proteins to cold
      acclimation. In addition, advanced techniques have given new insights into plasma
      membrane structural non-homogeneity, namely, microdomains. This chapter describes
      physiological implications of plasma membrane responses enhancing freezing
      tolerance during cold acclimation, with a focus on microdomains.

PMID- 30288705
TI  - Natural Variation in Freezing Tolerance and Cold Acclimation Response in
      Arabidopsis thaliana and Related Species.
AB  - During low-temperature exposure, temperate plant species increase their freezing
      tolerance in a process termed cold acclimation. The molecular mechanisms involved
      in cold acclimation have been mostly investigated in Arabidopsis thaliana. In
      addition, other Brassicaceae species related to A. thaliana have been employed in
      recent years to study plant stress responses on a phylogenetically broader basis
      and in some cases with extremophile species with a much higher stress tolerance.
      In this paper, we briefly summarize cold acclimation responses in A. thaliana and
      current knowledge about cold acclimation in A. thaliana relatives with special
      emphasis on Eutrema salsugineum and two closely related Thellungiella species. We
      then present a transcriptomic and metabolomic analysis of cold acclimation in
      five A. thaliana and two E. salsugineum accessions that differ widely in their
      freezing tolerance. Differences in the cold responses of the two species are
      discussed.

PMID- 30288706
TI  - Ice Nucleation Activity in Plants: The Distribution, Characterization, and Their
      Roles in Cold Hardiness Mechanisms.
AB  - Control of freezing in plant tissues is a key issue in cold hardiness mechanisms.
      Yet freeze-regulation mechanisms remain mostly unexplored. Among them, ice
      nucleation activity (INA) is a primary factor involved in the initiation and
      regulation of freezing events in plant tissues, yet the details remain poorly
      understood. To address this, we developed a highly reproducible assay for
      determining plant tissue INA and noninvasive freeze visualization tools using MRI
      and infrared thermography. The results of visualization studies on plant freezing
      behaviors and INA survey of over 600 species tissues show that (1) freezing
      sensitive plants tend to have low INA in their tissues (thus tend to transiently
      supercool), while wintering cold-hardy species have high INA in some specialized
      tissues; and (2) the high INA in cold-hardy tissues likely functions as a
      freezing sensor to initiate freezing at warm subzero temperatures at appropriate
      locations and timing, resulting in the induction of tissue-/species-specific
      freezing behaviors (e.g., extracellular freezing, extraorgan freezing) and the
      freezing order among tissues: from the primary freeze to the last tissue
      remaining unfrozen (likely INA level dependent). The spatiotemporal distributions
      of tissue INA, their characterization, and functional roles are detailed. INA
      assay principles, anti-nucleation activity (ANA), and freeze visualization tools
      are also described.

PMID- 30288707
TI  - Investigating Freezing Patterns in Plants Using Infrared Thermography.
AB  - Since the discovery of infrared radiation in 1800, the improvement of technology
      to detect and image infrared (IR) has led to numerous breakthroughs in several
      scientific fields of study. The principle that heat is released when water
      freezes and the ability to image this release of heat using IR thermography (IRT)
      has allowed an unprecedented understanding of freezing in plants. Since the first
      published report of the use of IRT to study freezing in plants, numerous
      informative discoveries have been reported. Examples include barriers to
      freezing, specific sites of ice nucleation, direction and speed of ice
      propagation, specific structures that supercool, and temperatures at which they
      finally freeze. These and other observations underscore the significance of this
      important technology on plant research.

PMID- 30288708
TI  - Mechanism of Overwintering in Trees.
AB  - Boreal trees possess very high freezing resistance, which is induced by short-day
      length and low temperatures, in order to survive severe subzero temperatures in
      winter. During autumn, cooperation of photoreceptors and circadian clock system
      perceiving photoperiod shortening results in growth cessation, dormancy
      development, and first induction of freezing resistance. The freezing resistance
      is further enhanced by subsequent low temperature during seasonal cold
      acclimation with concomitant changes in various morphological and physiological
      features including accumulation of sugars and late embryogenesis abundant
      proteins. The mechanism of adaptation to freezing temperatures differs depending
      on the type of tissue in boreal trees. For example, bark, cambium, and leaf cells
      tolerate freezing-induced dehydration by extracellular freezing, whereas xylem
      parenchyma cells avoid intracellular freezing by deep supercooling. In addition,
      dormant buds in some trees respond by extraorgan freezing. Boreal trees have
      evolved overwintering mechanisms such as dormancy and high freezing resistance in
      order to survive freezing temperatures in winter.

PMID- 30288709
TI  - The Mechanism of Low-Temperature Tolerance in Fish.
AB  - In this chapter, we cover the life history of fish in low-temperature
      environments, including their overwintering behavior and the physiological
      mechanisms by which they maintain life in cold environments, based on research to
      date. There is relatively little research on low-temperature tolerance of fish,
      compared with research on this phenomenon in mammals and birds, which are also
      vertebrates, and the mechanisms in fish have not been fully elucidated. First, we
      cover the life history of fish that overwinter by entering dormancy or
      hibernation. Next, we describe the mechanism that controls body temperature in
      fish that survive low-temperature environments. Finally, we introduce the
      physiological mechanisms for survival in extremely low-temperature environments,
      particularly antifreeze proteins.

PMID- 30288710
TI  - Mechanisms Underlying Freezing and Desiccation Tolerance in Bryophytes.
AB  - Bryophytes are small land plants that have many morphological and physiological
      features different from vascular plants. With distinct water relations of
      bryophytes, many bryophyte species exhibit high degrees of tolerance to freezing
      and desiccation. The tolerance is sustained by the constitutive repair mechanism
      and the inducible mechanism regulated by environmental signals that provoke
      specific responses within the cells. Bryophyte cells sense changes in
      environmental conditions such as decreases in osmotic potential and temperature
      and that some responses are likely to be mediated by the stress hormone, abscisic
      acid. Due to their simple structures and high degrees of dehydration tolerance,
      bryophytes are useful for physiological studies on abiotic stress response and
      also for analysis of signal sensing and transduction of environmental signals.
      Furthermore, the basal phylogenetic position of bryophytes in land plants
      provides many insights into the evolutionary events for conquest of land by the
      ancestors of plants and subsequent diversification of species as well as their
      survival strategies in the terrestrial environment.

PMID- 30288711
TI  - Regulatory Gene Networks in Drought Stress Responses and Resistance in Plants.
AB  - Plant responses to drought stress have been analyzed extensively to reveal
      complex regulatory gene networks, including the detection of water deficit
      signals, as well as the physiological, cellular, and molecular responses. Plants
      recognize water deficit conditions at their roots and transmit this signal to
      their shoots to synthesize abscisic acid (ABA) in their leaves. ABA is a key
      phytohormone that regulates physiological and molecular responses to drought
      stress, such as stomatal closure, gene expression, and the accumulation of
      osmoprotectants and stress proteins. ABA transporters function as the first step
      for propagating synthesized ABA. To prevent water loss, ABA influx in guard cells
      is detected by several protein kinases, such as SnRK2s and MAPKs that regulate
      stomatal closure. ABA mediates a wide variety of gene expression machineries with
      stress-responsive transcription factors, including DREBs and AREBs, to acquire
      drought stress resistance in whole tissues. In this chapter, we summarize recent
      advances in drought stress signaling, focusing on gene networks in cellular and
      intercellular stress responses and drought resistance.

PMID- 30288712
TI  - Mechanism of Stomatal Closure in Plants Exposed to Drought and Cold Stress.
AB  - Drought is one of the abiotic stresses which impairs the plant growth/development
      and restricts the yield of many crops throughout the world. Stomatal closure is a
      common adaptation response of plants to the onset of drought condition. Stomata
      are microscopic pores on the leaf epidermis, which regulate the transpiration/CO2
      uptake by leaves. Stomatal guard cells can sense various abiotic and biotic
      stress stimuli from the internal and external environment and respond quickly to
      initiate closure under unfavorable conditions. Stomata also limit the entry of
      pathogens into leaves, restricting their invasion. Drought is accompanied by the
      production and/or mobilization of the phytohormone, abscisic acid (ABA), which is
      well-known for its ability to induce stomatal closure. Apart from the ABA,
      various other factors that accumulate during drought and affect the stomatal
      function are plant hormones (auxins, MJ, ethylene, brassinosteroids, and
      cytokinins), microbial elicitors (salicylic acid, harpin, Flg 22, and chitosan),
      and polyamines . The role of various signaling components/secondary messengers
      during stomatal opening or closure has been a matter of intense investigation.
      Reactive oxygen species (ROS) , nitric oxide (NO) , cytosolic pH, and calcium are
      some of the well-documented signaling components during stomatal closure. The
      interrelationship and interactions of these signaling components such as ROS, NO,
      cytosolic pH, and free Ca2+ are quite complex and need further detailed
      examination.Low temperatures can have deleterious effects on plants. However,
      plants evolved protection mechanisms to overcome the impact of this stress. Cold
      temperature inhibits stomatal opening and causes stomatal closure. Cold
      acclimated plants often exhibit marked changes in their lipid composition,
      particularly of the membranes. Cold stress often leads to the accumulation of
      ABA, besides osmolytes such as glycine betaine and proline. The role of signaling
      components such as ROS, NO, and Ca2+ during cold acclimation is yet to be
      established, though the effects of cold stress on plant growth and development
      are studied extensively. The information on the mitigation processes is quite
      limited. We have attempted to describe consequences of drought and cold stress in
      plants, emphasizing stomatal closure. Several of these factors trigger signaling
      components in roots, shoots, and atmosphere, all leading to stomatal closure. A
      scheme is presented to show the possible signaling events and their convergence
      and divergence of action during stomatal closure. The possible directions for
      future research are discussed.

PMID- 30288713
TI  - Mechanisms of Maturation and Germination in Crop Seeds Exposed to Environmental
      Stresses with a Focus on Nutrients, Water Status, and Reactive Oxygen Species.
AB  - Environmental stresses can reduce crop yield and quality considerably. Plants
      protect cell metabolism in response to abiotic stresses at all stages of their
      life cycle, including seed production. As the production of vigorous seeds is
      important to both yield and crop growth, we analyzed causes of yield loss and
      reduced grain quality in staple crops exposed to environmental stresses such as
      drought and temperature extremes, with a focus on the remobilization of nutrients
      and water status during seed filling. Because water is one of the factors that
      limit seed development, seeds must have mechanisms that allow them to withstand
      water loss during seed maturation. In addition, analysis of the effects of
      reactive oxygen species (ROS) on transcription regulation and signaling should
      help to elucidate the regulation of seed dormancy and germination. In this
      review, we focus on nutrient remobilization, water mobility, plant hormones
      (gibberellins, abscisic acid, and ethylene), and ROS in sink and source organs
      and describe how rice, wheat, barley, soybean, and cowpea plants control seed
      maturation and germination under environmental stresses.

PMID- 30288714
TI  - The Antioxidant System in the Anhydrobiotic Midge as an Essential, Adaptive
      Mechanism for Desiccation Survival.
AB  - One of the major damaging factors for living organisms experiencing water
      insufficiency is oxidative stress. Loss of water causes a dramatic increase in
      the production of reactive oxygen species (ROS). Thus, the ability for some
      organisms to survive almost complete desiccation (called anhydrobiosis) is
      tightly related to the ability to overcome extraordinary oxidative stress. The
      most complex anhydrobiotic organism known is the larva of the chironomid
      Polypedilum vanderplanki. Its antioxidant system shows remarkable features, such
      as an expansion of antioxidant genes, their overexpression, as well as the
      absence or low expression of enzymes required for the synthesis of ascorbate and
      glutathione and their antioxidant function. In this chapter, we summarize
      existing data about the antioxidant system of this insect, which is able to cope
      with substantial oxidative damage, even in an intracellular environment that is
      severely disturbed due to water loss.

PMID- 30288715
TI  - Physicochemical Aspects of the Biological Functions of Trehalose and Group 3 LEA
      Proteins as Desiccation Protectants.
AB  - In this review, we first focus on the mechanism by which the larva of the
      sleeping chironomid, Polypedilum vanderplanki, survives an extremely dehydrated
      state and describe how trehalose and probably late embryogenesis abundant (LEA)
      proteins work as desiccation protectants. Second, we summarize the solid-state
      and solution properties of trehalose and discuss why trehalose works better than
      other disaccharides as a desiccation protectant. Third, we describe the structure
      and function of two model peptides based on group 3 LEA proteins after a short
      introduction of native LEA proteins themselves. Finally, we present our
      conclusions and a perspective on the application of trehalose and LEA model
      peptides to the long-term storage of biological materials.

PMID- 30288716
TI  - Supercooling-Promoting (Anti-ice Nucleation) Substances.
AB  - Studies on supercooling-promoting substances (SCPSs) are reviewed introducing
      name of chemicals, experimental conditions and the supercooling capability (SCC)
      in all, so far recognized, reported SCPSs and results of our original study are
      presented in order to totally show the functional properties of SCPSs which are
      known in the present state. Many kinds of substances have been identified as
      SCPSs that promote supercooling of aqueous solutions in a non-colligative manner
      by reducing the ice nucleation capability (INC) of ice nucleators (INs). The SCC
      as revealed by reduction of freezing temperature ( degrees C) by SCPSs differs
      greatly depending on the INs. While no single SCPS that affects homogeneous ice
      nucleation to reduce ice nucleation point has been found, many SCPSs have been
      found to reduce freezing temperatures by heterogeneous ice nucleation with a
      large fluctuation of SCC depending on the kind of heterogeneous IN. Not only
      SCPSs increase the degree of SCC ( degrees C), but also some SCPSs have
      additional SCC to stabilize a supercooling state for a long term to stabilize
      supercooling against strong mechanical disturbance and to reduce sublimation of
      ice crystals. The mechanisms underlying the diverse functions of SCPSs remain to
      be determined in future studies.

PMID- 30288718
TI  - Development and Application of Cryoprotectants.
AB  - Cryopreservation involves the preservation of biological materials, including
      cells, embryos, tissues, and organs, at ultra-low temperatures (in a state of
      suspended animation), for a long period of time, and in a way that allows them to
      be restored whenever required. Freezing of biological samples is generally
      accompanied by numerous undesirable outcomes such as intra- and extracellular
      freezing damage and osmotic stress. To prevent these adverse effects,
      cryoprotective agents (CPAs) are added to biological materials before freezing.
      Over the years, a number of CPAs have been identified and developed and have been
      employed successfully for numerous applications. Here, we review the history and
      development of cryoprotectants and the current understanding of the
      cryopreservation process. We conclude with a discussion about the application of
      cryopreservation for various clinical and academic studies.

PMID- 30288717
TI  - Applications of Antifreeze Proteins: Practical Use of the Quality Products from
      Japanese Fishes.
AB  - Numerous embryonic ice crystals are generated in water at the moment of freezing.
      These crystals grow and merge together to form an ice block that can be generally
      observed. Antifreeze protein (AFP) is capable of binding to the embryonic ice
      crystals, inhibiting such an ice block formation. Fish-derived AFP additionally
      binds to membrane lipid bilayers to prolong the lifetime of cells. These unique
      abilities of AFP have been studied extensively for the development of advanced
      techniques, such as ice recrystallization inhibitors, freeze-tolerant gels, cell
      preservation fluids, and high-porosity ceramics, for which mass-preparation
      method of the quality product of AFP utilizing fish muscle homogenates made a
      significant contribution. In this chapter, we present both fundamental and
      advanced information of fish AFPs that have been especially discovered from mid
      latitude sea area, which will provide a hint to develop more advanced techniques
      applicable in both medical and industrial fields.

PMID- 30288719
TI  - Cryopreservation of Plant Genetic Resources.
AB  - Cryopreservation encompasses several interconnect disciplines including
      physiology and cryophysics. This chapter reviews the current techniques for
      cryopreservation of plant genetic resources (PGRs). Vitrification is an effective
      ice crystal avoidance mechanism for hydrated cells and tissues. With any
      cryopreservation method, whole or partial parts of specimens which are
      sufficiently dehydrated can be vitrified by rapid cooling in liquid nitrogen
      (LN). Techniques discussed are the vitrification protocol, encapsulation
      vitrification protocol, droplet vitrification protocol (DV), vitrification
      protocol using cryo-plates (V cryo-plate), and air dehydration protocol using
      cryo-plates (D cryo-plate). In these DV, V, and D cryo-plate protocols, specimens
      to be cryopreserved are immersed directly into LN on aluminum foil strips or cryo
      plates; removal from LN to rewarming solution results in a high level of plant
      regrowth with ultrarapid cooling and warming. The protocols were applied to a
      wide array of plant species including wild and multi-ploid species, although fine
      tuning of the protocols was required for successful application to specific plant
      species and lines. These three protocols efficiently complement each other and
      appear highly promising to facilitate large-scale cryobanking of PGRs in
      genebanks. Cryo-scanning electron microscopy makes it possible to examine the
      cellular and water behavior in plant tissues when immersed in LN. It has been
      verified that tissues cryopreserved by the process of vitrification and the cryo
      plate protocols are cryopreservation methods for reliable long-term preservation
      of PGRs.

PMID- 30288720
TI  - Applications of Freezing and Freeze-Drying in Pharmaceutical Formulations.
AB  - Freeze-drying is a popular method to prepare pharmaceutical formulations
      containing structurally complex active ingredients and drug delivery system
      carriers. The solidification performed at lower temperature significantly
      improves storage stability of proteins, peptides, antibiotics, vaccines, and
      liposomes, which are marginally stable in aqueous solutions. Individual
      components of the freeze-drying process (freezing, primary drying, secondary
      drying), however, expose proteins to various stresses. Certain excipients,
      including disaccharides (e.g., sucrose, trehalose) and amino acids, can be added
      to protect the proteins and supramolecular drug delivery systems against physical
      stress associated with freezing and storage by substituting the molecular
      interactions provided by water molecules. Some excipients embed the active
      ingredients in glass-state solids with low molecular mobility, thereby reducing
      chemical reactivity. Thus, the use of appropriate excipients and process control
      is important to protect proteins during freeze-drying. This chapter describes the
      applications of freeze-drying in the pharmaceutical production process, mainly
      focusing on formulation and process optimization for protein therapeutics.

PMID- 30288721
TI  - Control of Physical Changes in Food Products.
AB  - Food is a multicomponent system that mainly comprises protein, carbohydrate, fat,
      and water. During food processing and preservation, various physical changes
      (e.g., melting, crystallization, glass transition) occur in food products,
      affecting their quality. This chapter specifically examines the effect of
      physical changes on the quality of dry and frozen food products. Dry food
      products are commonly in an amorphous state. Therefore, glass transition occurs
      during their dehydration-rehydration processing. To control their texture and
      physical stability, it is important to elucidate the effects of water contents on
      the glass transition temperature of dry food products. Frozen foods consist of
      ice crystals and freeze-concentrated matrix. The formation of ice crystal and the
      dynamics of ice crystal evolution affect food quality. Therefore control of ice
      crystals is important for high-quality frozen food. Moreover, because freeze
      concentrated matrix consists of solute that are plasticized by the unfrozen water
      and is in an amorphous state, it can undergo glass transition by freeze
      concentration. The physical state of freeze-concentrated matrix also strongly
      affects the stability of food quality during frozen storage.

PMID- 30288722
TI  - A Relational Ontology for Psychology: Life as an Asymmetric Subjet-Object
      Choosing Relation : Review of A New Logical Foundation for Psychology, J. Mammen,
      Springer, 2017.
AB  - This review of Mammen's new book (2017), provides a brief summary of the first
      part, stressing the main points of the author's constructive critique of the
      unfortunate issues psychology inherited from the atomistic mechanism of classical
      physics. Driving the discussion on the ontological level, Mammen briefly shows
      how nowadays natural sciences provide the main components psychology needs to
      overcome the everlasting crisis of psychology since its constitution as a
      science: discontinuity, contextuality, etc. Making of the relation between
      subject and object the foundation of any science, Mammen contributes to a new
      ontology specific to human study with elements of last century mathematics,
      notably the axiom of choice, bridging the rift between natural and human sciences
      with a continuum from inert matter to more or less advanced life forms. Mammen's
      constructive proposal opens the building site of a new foundation for life
      sciences, avoiding both simplistic mechanism and nihilist post-modernism.

PMID- 30288723
TI  - Hoop training: a pilot study assessing the effectiveness of a multisensory
      approach to treatment of body image disturbance in anorexia nervosa.
AB  - PURPOSE: We tested in a pilot study a new intervention for body image disturbance
      in anorexia nervosa (AN). Unlike common treatment approaches our hoop training
      targeted not only cognitive-emotional and visual aspects of body image, but also
      tactile and body-scaled action components. METHODS: We assessed cognitive,
      visual, tactile and body-scaled action aspects of body image disturbance before
      and after completion of hoop training. Twelve AN patients completed treatment as
      usual (TAU) for body image, 14 completed hoop training in addition to TAU.
      RESULTS: Results show that patients who completed the 8-week individual hoop
      training in addition to TAU improved more on body image disturbance tasks from
      baseline to follow-up than patients who completed only TAU. Hoop training
      specifically seems to affect tactile body image and body-scaled action.
      CONCLUSIONS: Taken together, a treatment approach in which the full spectrum of
      body image disturbances in AN is targeted has a unique added effect over
      treatment as usual. LEVEL OF EVIDENCE: Level II, non-randomized controlled study.

PMID- 30288724
TI  - How do you feel when you check your body? Emotional states during a body-checking
      episode in normal-weight females.
AB  - PURPOSE: Cognitive-behavioral theories posit that body checking decreases
      negative emotions, but increases levels of arousal. However, few studies have
      investigated the effects of body checking on the course of emotional states.
      Therefore, the current study examined how normal-weight females with higher and
      lower eating, weight, and shape concerns feel during a checking episode of their
      most-liked and least-liked body parts. METHODS: In an online design, levels of
      negative emotions and arousal were retrospectively assessed before, during,
      immediately after, and 15 min after an individually remembered body-checking
      episode. Participants (N = 355) also rated their subjective satisfaction with
      specific body parts. RESULTS: Levels of negative emotions were lower 15 min after
      the checking episode of most-liked and least-liked body parts than before the
      episode. However, negative emotions increased during the checking episode of
      least-liked body parts, but subsided thereafter. The levels of arousal increased
      during the checking episodes of most-liked and least-liked body parts and
      decreased afterwards, and females with higher concerns reported greater levels of
      arousal than females with lower concerns. Furthermore, females with higher
      concerns reported more body checking than those with lower concerns. CONCLUSIONS:
      The results support the assumptions of the cognitive-behavioral theories, as body
      checking led to a decrease in negative emotions in the longer term, and levels of
      arousal increased during the checking episode. The greater levels of arousal in
      females with higher concerns, and their pronounced body-checking behavior, might
      enhance their existing concerns and increase the risk of disordered eating. LEVEL
      OF EVIDENCE: Level V, descriptive study.

PMID- 30288725
TI  - Affect, reward, and punishment in anorexia nervosa: a narrative overview.
AB  - INTRODUCTION: Anorexia nervosa (AN) is a serious psychiatric disorder that is
      difficult to treat and often follows a protracted course. A number of theoretical
      models have been proposed for the etiology and maintenance of AN. Two domains
      that have received substantial attention in the literature on AN are affect and
      reward/punishment processes. However, despite an overlap in the nature and
      implications of these processes, studies of AN addressing these constructs have
      typically investigated them independently. PURPOSE: The purpose of this narrative
      review is to integrate the literature on the role of affect, reward, and
      punishment in AN. METHOD: We provide a focused narrative overview of the
      literature relating to the affect, reward, and punishment in AN via a synthesis
      of recent reviews and meta-analyses. RESULTS: We first describe several prominent
      affect and reward/punishment-based conceptualizations of AN, followed by a brief
      overview of the existing empirical literature in these domains. CONCLUSION: We
      provide a critical discussion of the disparate nature of these literatures in AN,
      including associated limitations. We then conclude with an extensive discussion
      of directions for future research that integrate the study of affect and
      reward/punishment processes in AN. LEVEL OF EVIDENCE: Level V, narrative review.

PMID- 30288728
TI  - International travel: A new guest in fertility counseling.

PMID- 30288726
TI  - In response to "missed opportunities and potentially misleading results in
      maternal mortality study".

PMID- 30288727
TI  - Pelvic floor muscle training versus no treatment, or inactive control treatments,
      for urinary incontinence in women.
AB  - BACKGROUND: Pelvic floor muscle training (PFMT) is the most commonly used
      physical therapy treatment for women with stress urinary incontinence (SUI). It
      is sometimes also recommended for mixed urinary incontinence (MUI) and, less
      commonly, urgency urinary incontinence (UUI).This is an update of a Cochrane
      Review first published in 2001 and last updated in 2014. OBJECTIVES: To assess
      the effects of PFMT for women with urinary incontinence (UI) in comparison to no
      treatment, placebo or sham treatments, or other inactive control treatments; and
      summarise the findings of relevant economic evaluations. SEARCH METHODS: We
      searched the Cochrane Incontinence Specialised Register (searched 12 February
      2018), which contains trials identified from CENTRAL, MEDLINE, MEDLINE In
      Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP,
      handsearching of journals and conference proceedings, and the reference lists of
      relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled
      trials in women with SUI, UUI or MUI (based on symptoms, signs or urodynamics).
      One arm of the trial included PFMT. Another arm was a no treatment, placebo, sham
      or other inactive control treatment arm. DATA COLLECTION AND ANALYSIS: At least
      two review authors independently assessed trials for eligibility and risk of
      bias. We extracted and cross-checked data. A third review author resolved
      disagreements. We processed data as described in the Cochrane Handbook for
      Systematic Reviews of Interventions. We subgrouped trials by diagnosis of UI. We
      undertook formal meta-analysis when appropriate. MAIN RESULTS: The review
      included 31 trials (10 of which were new for this update) involving 1817 women
      from 14 countries. Overall, trials were of small-to-moderate size, with follow
      ups generally less than 12 months and many were at moderate risk of bias. There
      was considerable variation in the intervention's content and duration, study
      populations and outcome measures. There was only one study of women with MUI and
      only one study with UUI alone, with no data on cure, cure or improvement, or
      number of episodes of UI for these subgroups.Symptomatic cure of UI at the end of
      treatment: compared with no treatment or inactive control treatments, women with
      SUI who were in the PFMT groups were eight times more likely to report cure (56%
      versus 6%; risk ratio (RR) 8.38, 95% confidence interval (CI) 3.68 to 19.07; 4
      trials, 165 women; high-quality evidence). For women with any type of UI, PFMT
      groups were five times more likely to report cure (35% versus 6%; RR 5.34, 95% CI
      2.78 to 10.26; 3 trials, 290 women; moderate-quality evidence).Symptomatic cure
      or improvement of UI at the end of treatment: compared with no treatment or
      inactive control treatments, women with SUI who were in the PFMT groups were six
      times more likely to report cure or improvement (74% versus 11%; RR 6.33, 95% CI
      3.88 to 10.33; 3 trials, 242 women; moderate-quality evidence). For women with
      any type of UI, PFMT groups were two times more likely to report cure or
      improvement than women in the control groups (67% versus 29%; RR 2.39, 95% CI
      1.64 to 3.47; 2 trials, 166 women; moderate-quality evidence).UI-specific
      symptoms and quality of life (QoL) at the end of treatment: compared with no
      treatment or inactive control treatments, women with SUI who were in the PFMT
      group were more likely to report significant improvement in UI symptoms (7
      trials, 376 women; moderate-quality evidence), and to report significant
      improvement in UI QoL (6 trials, 348 women; low-quality evidence). For any type
      of UI, women in the PFMT group were more likely to report significant improvement
      in UI symptoms (1 trial, 121 women; moderate-quality evidence) and to report
      significant improvement in UI QoL (4 trials, 258 women; moderate-quality
      evidence). Finally, for women with mixed UI treated with PFMT, there was one
      small trial (12 women) reporting better QoL.Leakage episodes in 24 hours at the
      end of treatment: PFMT reduced leakage episodes by one in women with SUI (mean
      difference (MD) 1.23 lower, 95% CI 1.78 lower to 0.68 lower; 7 trials, 432 women;
      moderate-quality evidence) and in women with all types of UI (MD 1.00 lower, 95%
      CI 1.37 lower to 0.64 lower; 4 trials, 349 women; moderate-quality
      evidence).Leakage on short clinic-based pad tests at the end of treatment: women
      with SUI in the PFMT groups lost significantly less urine in short (up to one
      hour) pad tests. The comparison showed considerable heterogeneity but the
      findings still favoured PFMT when using a random-effects model (MD 9.71 g lower,
      95% CI 18.92 lower to 0.50 lower; 4 trials, 185 women; moderate-quality
      evidence). For women with all types of UI, PFMT groups also reported less urine
      loss on short pad tests than controls (MD 3.72 g lower, 95% CI 5.46 lower to 1.98
      lower; 2 trials, 146 women; moderate-quality evidence).Women in the PFMT group
      were also more satisfied with treatment and their sexual outcomes were better.
      Adverse events were rare and, in the two trials that did report any, they were
      minor. The findings of the review were largely supported by the 'Summary of
      findings' tables, but most of the evidence was downgraded to moderate on
      methodological grounds. The exception was 'participant-perceived cure' in women
      with SUI, which was rated as high quality. AUTHORS' CONCLUSIONS: Based on the
      data available, we can be confident that PFMT can cure or improve symptoms of SUI
      and all other types of UI. It may reduce the number of leakage episodes, the
      quantity of leakage on the short pad tests in the clinic and symptoms on UI
      specific symptom questionnaires. The authors of the one economic evaluation
      identified for the Brief Economic Commentary reported that the cost-effectiveness
      of PFMT looks promising. The findings of the review suggest that PFMT could be
      included in first-line conservative management programmes for women with UI. The
      long-term effectiveness and cost-effectiveness of PFMT needs to be further
      researched.

PMID- 30288729
TI  - Slavery and institutional morality at Georgetown University: Reply to Nelson.

PMID- 30288730
TI  - Early parenting predicts hippocampal subregion volume via stress reactivity in
      childhood.
AB  - Rodent models indicate that parenting shapes offspring outcomes by programming
      the hypothalamic-pituitary-adrenal axis response to stress and, ultimately,
      altering brain structure and function. The present study tested this hypothesis
      and explored possible timing-dependent associations in a longitudinal sample of
      children (N = 63). At Time 1 (M = 4.23 +/- 0.84 years) and Time 2 (M = 7.20 +/-
      0.89 years), children completed parent-child interaction tasks and a laboratory
      stressor after which salivary cortisol samples were collected. At Time 2,
      children also completed a structural MRI. Analyses revealed timing- and region
      dependent associations between early and concurrent parenting and cortisol
      reactivity and hippocampal subregion volumes. Moreover, greater negative
      parenting during early childhood predicted greater cortisol reactivity three
      years later, which, in turn, led to reduced left hippocampal tail volume.
      Findings suggest that the hippocampus is sensitive to environmental influences
      during early childhood, a result that parallels findings from rodent models.

PMID- 30288731
TI  - Use of intrapartum ultrasound in term pregnant women with contractions before
      hospital admission.
AB  - INTRODUCTION: The aim of this study was to test the hypothesis that transperineal
      ultrasound can be used to decide whether to admit a pregnant woman due to labor.
      MATERIAL AND METHODS: In this analytical cross-sectional observational study,
      transperineal ultrasound was performed on pregnant women with intact membranes
      who came to the hospital due to contractions. A decision was made to admit women
      due to labor based on the ultrasound measurements. The ultrasound measurements
      were used to determine cervical dilation, the angle of progression, and fetal
      head position. The managing midwives were blinded to the results and made the
      final decision to admit the women based on digital vaginal examination. RESULTS:
      It was possible to decide whether a woman had to be admitted for delivery or
      discharged due to the latent phase of labor according to the ultrasound
      examination in 55 of the 57 cases (96.5%). In 4 of the 55 cases, the decision
      based on ultrasound differed from the midwife's decision (7.3%). There was strong
      agreement between the decision to admit the pregnant women based on ultrasound
      measurements and the digital vaginal examination (Cohen's kappa: 0.844). It was
      possible to measure cervical dilation with ultrasound in 52 of the 57 cases
      (91.2%). The intraclass correlation coefficient for the cervical dilation
      measurements was 0.736 (95% confidence interval 0.539-0.848). CONCLUSIONS: There
      was strong agreement between the ultrasound and digital vaginal examination
      results in the decision to admit singleton pregnant women at term due to labor. A
      large number of vaginal examinations could be avoided by using intrapartum
      ultrasound.

PMID- 30288732
TI  - Repetitive neonatal pain and reduced maternal care alter brain neurochemistry.
AB  - Preterm infants are exposed to many stressors while in the neonatal intensive
      care unit including pain and reduced maternal care. Both stressors can have a
      profound negative impact on brain development, and the present study sought to
      investigate some of the biological mechanisms underlying this phenomenon. Rat
      pups underwent a series of repetitive needle pokes and/or reduced maternal care
      through a novel tea-ball infuser encapsulation model during the first four days
      of life. On postnatal day four, pups were sacrificed and serum was analyzed for
      corticosterone, while brains were tested for various neurotransmitters and brain
      metabolites through magnetic resonance spectroscopy. We found that exposure to
      maternal isolation and neonatal pain produced an increase in serum corticosterone
      but decreased glutamate levels in the hippocampus and frontal cortex. These
      alterations in stress responding and neurochemistry in response to the early-life
      stressors may help explain some of the negative outcomes seen in preterm infants.

PMID- 30288733
TI  - Interpregnancy interval and abnormally invasive placentation.
AB  - INTRODUCTION: The presence of a previous uterine scar is a strong risk factor for
      developing abnormally invasive placentation (AIP). We sought to determine whether
      a short interpregnancy interval predisposes to AIP. We hypothesized that a short
      interpregnancy interval after a previous cesarean delivery increases the risk of
      AIP in comparison with a longer interpregnancy interval. MATERIAL AND METHODS: We
      performed a retrospective cohort study of women with a histological diagnosis of
      AIP and a history of a previous cesarean section. Women were included in the
      control group if they had a previous cesarean section with a placenta underlying
      the previous uterine scar or an anterior previa. The time interval between
      pregnancy and AIP data was analyzed using the chi-square test and two-tailed
      Fisher's exact test. RESULTS: There was no statistical difference in the
      interpregnancy interval between women who had AIP vs the control group. Gravidity
      and parity were found to be significantly higher in the women with AIP vs the
      controls. CONCLUSIONS: These results suggest that a short interpregnancy interval
      may not increase the risk of developing AIP.

PMID- 30288734
TI  - Editorial - Maori's women's health in New Zealand.

PMID- 30288735
TI  - Novel exostosin-2 missense variants in a family with autosomal recessive
      exostosin-2-related syndrome: further evidences on the phenotype.
AB  - Biallelic exostosin-2 (EXT2) pathogenic variants have been described as the cause
      of the Seizures-Scoliosis-Macrocephaly syndrome (OMIM 616682) characterized by
      intellectual disability, facial dysmorphisms and seizures. More recently, it has
      been proposed to rename this disorder with the acronym AREXT2 (autosomal
      recessive EXT2-related syndrome). Here, we report the third family affected by
      AREXT2 syndrome, harboring compound missense variants in EXT2, p.Asp227Asn, and
      p.Tyr608Cys. In addition, our patients developed multiple exostoses, which were
      not observed in the previously described families. AREXT2 syndrome can be
      considered as a multiorgan Congenital Disorder of Glycosylation caused by a
      significant, but non-lethal, decrease in EXT2 expression, thereby affecting the
      synthesis of the heparan sulfate proteoglycans, which is relevant in many
      physiological processes. Our finding expands the clinical and molecular spectrum
      of the AREXT2 syndrome and suggests a possible genotype/phenotype correlation in
      the development of the exostoses.

PMID- 30288736
TI  - Supraglottic airway devices in difficult airway management: a retrospective
      cohort study of 658,104 general anaesthetics registered in the Danish Anaesthesia
      Database.
AB  - Indications for using supraglottic airway devices have widened over time and they
      now hold a prominent role in guidelines for difficult airway management. We aimed
      to describe the use of supraglottic airway devices in difficult airway
      management. We included adult patients undergoing general anaesthesia registered
      in the Danish Anaesthesia Database from 2008 to 2012 whose airway management had
      been recorded as difficult, defined as: >= 3 tracheal intubation attempts; failed
      tracheal intubation; or difficult facemask ventilation. In the Danish Anaesthesia
      Database, a separate difficult airway management module requires the technique
      used in each successive airway management attempt to be recorded. The primary aim
      of the study was to describe the use of supraglottic airway devices in cases of
      difficult airway management. Secondary aims were to examine success rates of
      supraglottic airway devices in difficult airway management cases, and
      specifically in the cases of 'cannot intubate, cannot facemask ventilate'.
      Difficult airway management occurred in 4898 (0.74% (95%CI 0.72-0.76%)) of
      658,104 records of general anaesthesia. Supraglottic airway devices were used or
      use was attempted in 607 cases of difficult airway management (12.4% (95%CI 11.5
      13.3%)), and were successful in 395 (65.1% (95%CI 61.2-68.8%)) cases. In 'cannot
      intubate, cannot facemask ventilate' situations, supraglottic airway devices were
      used in 86 (18.9% (95%CI 15.6-22.8%)) of 455 records and were successful in 54
      (62.8% (95%CI 52.2-72.3%)) cases. We found that supraglottic airway devices are
      not widely used in the management of the difficult airway despite their prominent
      role in difficult airway management guidelines.

PMID- 30288737
TI  - The uses of disorder in negotiated information orders: information leveraging and
      changing norms in global public health governance.
AB  - The SARS epidemic that broke out in late 2002 in China's Guangdong Province
      highlighted the difficulties of reliance on state-provided information when
      states have incentives to conceal discrediting information about public health
      threats. Using SARS and the International Health Regulations (IHR) as a starting
      point, this article examines negotiated information orders in global public
      health governance and the irregularities in the supply of data that underlie
      them. Negotiated information orders within and among the organizations in a field
      (here, e.g., the World Health Organization, member states, government agencies,
      and international non-governmental organizations) spell out relationships among
      different categories of knowledge and non-knowledge - what is known, acknowledged
      to be known, and available for use in decision making versus what might be known
      but cannot be acknowledged or officially used. Through information leveraging,
      technically sufficient information then becomes socially sufficient information.
      Thus it is especially information initially categorized as non-knowledge -
      including suppressed data, rumour, unverified evidence, and unofficial
      information - that creates pressure for the renegotiation of information orders.
      The argument and evidence of the article also address broader issues about how
      international law and global norms are realigned, how global norms change, and
      how social groups manage risk.

PMID- 30288738
TI  - Individual-, family-, and school-level interventions targeting multiple risk
      behaviours in young people.
AB  - BACKGROUND: Engagement in multiple risk behaviours can have adverse consequences
      for health during childhood, during adolescence, and later in life, yet little is
      known about the impact of different types of interventions that target multiple
      risk behaviours in children and young people, or the differential impact of
      universal versus targeted approaches. Findings from systematic reviews have been
      mixed, and effects of these interventions have not been quantitatively estimated.
      OBJECTIVES: To examine the effects of interventions implemented up to 18 years of
      age for the primary or secondary prevention of multiple risk behaviours among
      young people. SEARCH METHODS: We searched 11 databases (Australian Education
      Index; British Education Index; Campbell Library; Cumulative Index to Nursing and
      Allied Health Literature (CINAHL); Cochrane Central Register of Controlled Trials
      (CENTRAL), in the Cochrane Library; Embase; Education Resource Information Center
      (ERIC); International Bibliography of the Social Sciences; MEDLINE; PsycINFO; and
      Sociological Abstracts) on three occasions (2012, 2015, and 14 November 2016)).
      We conducted handsearches of reference lists, contacted experts in the field,
      conducted citation searches, and searched websites of relevant organisations.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs), including
      cluster RCTs, which aimed to address at least two risk behaviours. Participants
      were children and young people up to 18 years of age and/or parents, guardians,
      or carers, as long as the intervention aimed to address involvement in multiple
      risk behaviours among children and young people up to 18 years of age. However,
      studies could include outcome data on children > 18 years of age at the time of
      follow-up. Specifically,we included studies with outcomes collected from those
      eight to 25 years of age. Further, we included only studies with a combined
      intervention and follow-up period of six months or longer. We excluded
      interventions aimed at individuals with clinically diagnosed disorders along with
      clinical interventions. We categorised interventions according to whether they
      were conducted at the individual level; the family level; or the school level.
      DATA COLLECTION AND ANALYSIS: We identified a total of 34,680 titles, screened
      27,691 articles and assessed 424 full-text articles for eligibility. Two or more
      review authors independently assessed studies for inclusion in the review,
      extracted data, and assessed risk of bias.We pooled data in meta-analyses using a
      random-effects (DerSimonian and Laird) model in RevMan 5.3. For each outcome, we
      included subgroups related to study type (individual, family, or school level,
      and universal or targeted approach) and examined effectiveness at up to 12
      months' follow-up and over the longer term (> 12 months). We assessed the quality
      and certainty of evidence using the Grades of Recommendation, Assessment,
      Development and Evaluation (GRADE) approach. MAIN RESULTS: We included in the
      review a total of 70 eligible studies, of which a substantial proportion were
      universal school-based studies (n = 28; 40%). Most studies were conducted in the
      USA (n = 55; 79%). On average, studies aimed to prevent four of the primary
      behaviours. Behaviours that were most frequently addressed included alcohol use
      (n = 55), drug use (n = 53), and/or antisocial behaviour (n = 53), followed by
      tobacco use (n = 42). No studies aimed to prevent self-harm or gambling alongside
      other behaviours.Evidence suggests that for multiple risk behaviours, universal
      school-based interventions were beneficial in relation to tobacco use (odds ratio
      (OR) 0.77, 95% confidence interval (CI) 0.60 to 0.97; n = 9 studies; 15,354
      participants) and alcohol use (OR 0.72, 95% CI 0.56 to 0.92; n = 8 studies; 8751
      participants; both moderate-quality evidence) compared to a comparator, and that
      such interventions may be effective in preventing illicit drug use (OR 0.74, 95%
      CI 0.55 to 1.00; n = 5 studies; 11,058 participants; low-quality evidence) and
      engagement in any antisocial behaviour (OR 0.81, 95% CI 0.66 to 0.98; n = 13
      studies; 20,756 participants; very low-quality evidence) at up to 12 months'
      follow-up, although there was evidence of moderate to substantial heterogeneity
      (I2 = 49% to 69%). Moderate-quality evidence also showed that multiple risk
      behaviour universal school-based interventions improved the odds of physical
      activity (OR 1.32, 95% CI 1.16 to 1.50; I2 = 0%; n = 4 studies; 6441
      participants). We considered observed effects to be of public health importance
      when applied at the population level. Evidence was less certain for the effects
      of such multiple risk behaviour interventions for cannabis use (OR 0.79, 95% CI
      0.62 to 1.01; P = 0.06; n = 5 studies; 4140 participants; I2 = 0%; moderate
      quality evidence), sexual risk behaviours (OR 0.83, 95% CI 0.61 to 1.12; P =
      0.22; n = 6 studies; 12,633 participants; I2 = 77%; low-quality evidence), and
      unhealthy diet (OR 0.82, 95% CI 0.64 to 1.06; P = 0.13; n = 3 studies; 6441
      participants; I2 = 49%; moderate-quality evidence). It is important to note that
      some evidence supported the positive effects of universal school-level
      interventions on three or more risk behaviours.For most outcomes of individual-
      and family-level targeted and universal interventions, moderate- or low-quality
      evidence suggests little or no effect, although caution is warranted in
      interpretation because few of these studies were available for comparison (n <= 4
      studies for each outcome).Seven studies reported adverse effects, which involved
      evidence suggestive of increased involvement in a risk behaviour among
      participants receiving the intervention compared to participants given control
      interventions.We judged the quality of evidence to be moderate or low for most
      outcomes, primarily owing to concerns around selection, performance, and
      detection bias and heterogeneity between studies. AUTHORS' CONCLUSIONS: Available
      evidence is strongest for universal school-based interventions that target
      multiple- risk behaviours, demonstrating that they may be effective in preventing
      engagement in tobacco use, alcohol use, illicit drug use, and antisocial
      behaviour, and in improving physical activity among young people, but not in
      preventing other risk behaviours. Results of this review do not provide strong
      evidence of benefit for family- or individual-level interventions across the risk
      behaviours studied. However, poor reporting and concerns around the quality of
      evidence highlight the need for high-quality multiple- risk behaviour
      intervention studies to further strengthen the evidence base in this field.

PMID- 30288739
TI  - Inhaled nitric oxide.
AB  - Nitric oxide (NO) is a gas that induces relaxation of smooth muscle cells in the
      vasculature. Because NO reacts with oxyhaemoglobin with high affinity, the gas is
      rapidly scavenged by oxyhaemoglobin in red blood cells and the vasodilating
      effects of inhaled NO are limited to ventilated regions in the lung. NO therefore
      has the unique ability to induce pulmonary vasodilatation specifically in the
      portions of the lung with adequate ventilation, thereby improving oxygenation of
      blood and decreasing intrapulmonary right to left shunting. Inhaled NO is used to
      treat a spectrum of cardiopulmonary conditions, including pulmonary hypertension
      in children and adults. However, the widespread use of inhaled NO is limited by
      logistical and financial barriers. We have designed, developed and tested a
      simple and economic NO generation device, which uses pulsed electrical discharges
      in air to produce therapeutic levels of NO that can be used for inhalation
      therapy.

PMID- 30288740
TI  - An unusual presentation of rectal carcinoma with group G streptococcal sepsis in
      the early third trimester.

PMID- 30288741
TI  - The effect of force applied to the left paratracheal oesophagus on air entry into
      the gastric antrum during positive-pressure ventilation using a facemask.
AB  - Cricoid force is widely applied to decrease the risk of pulmonary aspiration and
      gastric antral insufflation of air during positive-pressure ventilation, yet its
      efficacy remains controversial. We compared manual oesophageal compression at the
      low left paratracheal and cricoid levels for the prevention of gastric antral air
      insufflation during positive-pressure ventilation by facemask in patients
      scheduled for elective surgery under general anaesthesia. After gaining written
      consent, participants were randomly allocated by sealed envelope to one of three
      groups: oesophageal compression by 30 N paratracheal force (paratracheal group);
      oesophageal compression by 30 N cricoid force (cricoid group); or no oesophageal
      compression (control group). Gastric insufflation of air was assessed before and
      after positive-pressure ventilation by ultrasound measurement of the antral cross
      sectional area and/or presence of air artefacts in the antrum. The primary
      outcome measure was the proportion of participants with ultrasound evidence of
      gastric insufflation. We recruited 30 patients into each group. Before facemask
      ventilation, no air artefacts were visible in the antrum in any of the
      participants. After facemask ventilation of the participant's lungs, no air
      artefacts were seen in the paratracheal group, compared with six subjects in the
      cricoid group and eight subjects in the control group (p = 0.012). Our results
      suggest that oesophageal compression can be achieved by the application of manual
      force at the low left paratracheal level and that this is more effective than
      cricoid force in preventing air entry into the gastric antrum during positive
      pressure ventilation by facemask.

PMID- 30288742
TI  - An analysis of a multiple biomarker panel to better predict prostate cancer
      metastasis after radical prostatectomy.
AB  - A plethora of individual candidate biomarkers for predicting biochemical relapse
      in localized prostate cancer (PCa) have been proposed. Combined biomarkers may
      improve prognostication, and ensuring validation against more clinically relevant
      endpoints are required. The Australian PCa Research Centre NSW has contributed to
      numerous studies of molecular biomarkers associated with biochemical relapse. In
      the current study, these biomarkers were re-analyzed for biochemical relapse,
      metastatic relapse and PCa death with extended follow-up. Biomarkers of
      significance were then used to develop a combined prognostic model for clinical
      outcomes and validated in a large independent cohort. The discovery cohort (n =
      324) was based on 12 biomarkers with a median follow-up of 16 years. Seven
      biomarkers were significantly associated with biochemical relapse. Three
      biomarkers were associated with metastases: AZGP1, Ki67 and PML. Only AZGP1 was
      associated with PCa death. In their individual and combinational forms, AZGP1 and
      Ki67 as a dual BM signature was the most robust predictor of metastatic relapse
      (AUC 0.762). The AZPG1 and Ki67 signature was validated in an independent cohort
      of 347 PCa patients. The dual BM signature of AZGP1 and Ki67 predicted metastasis
      in the univariable (HR 7.2, 95% CI, 1.6-32; p = 0.01) and multivariable analysis
      (HR 5.4, 95% CI, 1.2-25; p = 0.03). The dual biomarker signature marginally
      improved risk prediction compared to AZGP1 alone (AUC 0.758 versus 0.738, p <
      0.001). Our findings indicate that biochemical relapse is not an adequate
      surrogate for metastasis or PCa death. The dual biomarker signature of AZGP1 and
      Ki67 offers a small benefit in predicting metastasis over AZGP1 alone.

PMID- 30288743
TI  - Pathogen enrichment sequencing (PenSeq) enables population genomic studies in
      oomycetes.
AB  - The oomycete pathogens Phytophthora infestans and P. capsici cause significant
      crop losses world-wide, threatening food security. In each case, pathogenicity
      factors, called RXLR effectors, contribute to virulence. Some RXLRs are perceived
      by resistance proteins to trigger host immunity, but our understanding of the
      demographic processes and adaptive evolution of pathogen virulence remains poor.
      Here, we describe PenSeq, a highly efficient enrichment sequencing approach for
      genes encoding pathogenicity determinants which, as shown for the infamous potato
      blight pathogen Phytophthora infestans, make up < 1% of the entire genome. PenSeq
      facilitates the characterization of allelic diversity in pathogen effectors,
      enabling evolutionary and population genomic analyses of Phytophthora species.
      Furthermore, PenSeq enables the massively parallel identification of
      presence/absence variations and sequence polymorphisms in key pathogen genes,
      which is a prerequisite for the efficient deployment of host resistance genes.
      PenSeq represents a cost-effective alternative to whole-genome sequencing and
      addresses crucial limitations of current plant pathogen population studies, which
      are often based on selectively neutral markers and consequently have limited
      utility in the analysis of adaptive evolution. The approach can be adapted to
      diverse microbes and pathogens.

PMID- 30288744
TI  - Sadder but wiser: Emotional reactions and wisdom in a simulated suicide
      intervention.
AB  - Scholars within the Berlin paradigm have analysed participants' responses to a
      hypothetical vignette about a friend's suicide ideation. However, no study has
      yet focused on participants' emotional reactions to this scenario, an important
      aspect of wisdom performance. We conducted a Thin-Slice Wisdom study where
      participants were asked to give advice to a hypothetical friend contemplating
      suicide. We analysed their emotional profiles using facial expression analysis
      software (FACET2.1 and FACEREADER7.1). Participants' verbal responses were also
      transcribed and then scored by 10 raters using the Berlin criteria. Results
      revealed that the sadder the participants felt, the wiser their performance.
      Wiser participants may have been better at exploring this sad, but true,
      existential human dilemma.

PMID- 30288745
TI  - Comparative characterization of putative chitin deacetylases from Phaeodactylum
      tricornutum and Thalassiosira pseudonana highlights the potential for distinct
      chitin-based metabolic processes in diatoms.
AB  - Chitin is generally considered to be present in centric diatoms but not in
      pennate species. Many aspects of chitin biosynthetic pathways have not been
      explored in diatoms. We retrieved chitin metabolic genes from pennate
      (Phaeodactylum tricornutum) and centric (Thalassiosira pseudonana) diatom
      genomes. Chitin deacetylase (CDA) genes from each genome (PtCDA and TpCDA) were
      overexpressed in P. tricornutum. We performed comparative analysis of their
      sequence structure, phylogeny, transcriptional profiles, localization and
      enzymatic activities. The chitin relevant proteins show complex subcellular
      compartmentation. PtCDA was likely acquired by horizontal gene transfer from
      prokaryotes, whereas TpCDA has closer relationships with sequences in
      Opisthokonta. Using transgenic P. tricornutum lines expressing CDA-green
      fluorescent protein (GFP) fusion proteins, PtCDA predominantly localizes to Golgi
      apparatus whereas TpCDA localizes to endoplasmic reticulum/chloroplast
      endoplasmic reticulum membrane. CDA-GFP overexpression upregulated the
      transcription of chitin synthases and potentially enhanced the ability of chitin
      synthesis. Although both CDAs are active on GlcNAc5 , TpCDA is more active on the
      highly acetylated chitin polymer DA60. We have addressed the ambiguous characters
      of CDAs from P. tricornutum and T. pseudonana. Differences in localization,
      evolution, expression and activities provide explanations underlying the greater
      potential of centric diatoms for chitin biosynthesis. This study paves the way
      for in vitro applications of novel CDAs.

PMID- 30288746
TI  - Evolution and expression of core SWI/SNF genes in red algae.
AB  - Red algae are the oldest identifiable multicellular eukaryotes, with a fossil
      record dating back more than a billion years. During that time two major
      rhodophyte lineages, bangiophytes and florideophytes, have evolved varied levels
      of morphological complexity. These two groups are distinguished, in part, by
      different patterns of multicellular development, with florideophytes exhibiting a
      far greater diversity of morphologies. Interestingly, during their long
      evolutionary history, there is no record of a rhodophyte achieving the kinds of
      cellular and tissue-specific differentiation present in other multicellular algal
      lineages. To date, the genetic underpinnings of unique aspects of red algal
      development are largely unexplored; however, they must reflect the complements
      and patterns of expression of key regulatory genes. Here we report comparative
      evolutionary and gene expression analyses of core subunits of the SWI/SNF
      chromatin-remodeling complex, which is implicated in cell differentiation and
      developmental regulation in more well studied multicellular groups. Our results
      suggest that a single, canonical SWI/SNF complex was present in the rhodophyte
      ancestor, with gene duplications and evolutionary diversification of SWI/SNF
      subunits accompanying the evolution of multicellularity in the common ancestor of
      bangiophytes and florideophytes. Differences in how SWI/SNF chromatin remodeling
      evolved subsequently, in particular gene losses and more rapid divergence of SWI3
      and SNF5 in bangiophytes, could help to explain why they exhibit a more limited
      range of morphological complexity than their florideophyte cousins.

PMID- 30288747
TI  - Transcriptomic analysis reveals the possible roles of sugar metabolism and export
      for positive mycorrhizal growth responses in soybean.
AB  - To elucidate molecular mechanisms controlling differential growth responses to
      root colonization by arbuscular mycorrhizal (AM) fungi varying in colonization
      and cooperative behavior, a pot experiment was carried out using two soybean
      genotypes and three AM inocula. The results showed that inoculation by
      cooperative Rhizophagus irregularis (Ri) or less cooperative Glomus aggregatum
      with high AM colonization (Ga-H) significantly promoted plant growth compared
      with inoculation by G. aggregatum with low AM colonization (Ga-L). A comparative
      RNA sequencing analysis of the root transcriptomes showed that fatty acid
      synthesis pathway was significantly enriched in all three AM inoculation roots.
      However, sugar metabolism and transport were significantly enriched only in Ri
      and Ga-H inoculation, which was consistent with positive growth responses in
      these two inoculation treatments. Accordingly, the expression levels of the key
      genes related to sugar metabolism and transport were also upregulated in Ri and
      Ga-H roots compared with Ga-L roots. Of them, two sugars will eventually be
      exported transporters (SWEET) transporter genes, GmSWEET6 (Glyma.04G198600) and
      GmSWEET15 (Glyma.06G166800), and one invertase (Glyma.17G227900) gene were
      exclusively induced only in Ri and Ga-H roots. Promoter analyses in transgenic
      soybean roots further demonstrated that GUS driven by the GmSWEET6 promoter was
      highly expressed in arbuscule-containing cortical cells. Additionally, Ri and Ga
      H inoculation increased the contents of sucrose, glucose and fructose in both
      shoots and roots compared with those of Ga-L and non-mycorrhizal. These results
      imply that positive mycorrhizal growth responses in plants might mostly be due to
      the stimulation of photosynthate metabolism and transport by AM fungal inoculum
      with high colonization capabilities.

PMID- 30288748
TI  - Avoiding damage to transvenous leads-A comparison of electrocautery techniques
      and two insulated electrocautery blades.
AB  - BACKGROUND: Electrocautery (cautery) can damage transvenous cardiac device leads.
      The purpose of this study was to compare lead damage from an insulated cautery
      blade when used with several different techniques that included coagulation
      (COAG) versus cutting (CUT) mode, perpendicular active edge (active) versus
      parallel flat blade (flat) orientation (phase 1), and using one commercially
      available blade (PhotonBlade) versus another (PlasmaBlade) (phase 2). METHODS: In
      phase 1, lesions were delivered using combinations of: (1) COAG and CUT; (2)
      active and flat orientation; and (3) polyurethane, silicone, and copolymer
      insulation. In phase 2, lesions were delivered using combinations of: (1)
      PlasmaBlade and PhotonBlade, (2) four power output levels, and (3) eight
      different lead models. Lead damage was scored on an ordinal scale of 0 to 4.
      RESULTS: Phase 1: more leads were damaged using COAG than CUT (48% vs 2%, P <
      0.0001). When using COAG, 74% of lesions using active orientation had damage
      versus 22% of lesions using flat orientation (P  =  0.0002). COAG lesions to
      copolymer (61%) and polyurethane (68%) leads had greater damage than silicone
      (17%) (P  =  0.006 and P  =  0.003, respectively). Phase 2: 75% of treatments
      using PlasmaBlade had damage versus 40% of treatments with PhotonBlade (P <
      0.0001). Higher power resulted in more damage. At the commonly used setting of
      CUT 20 W, damage occurred in 39% of treatments using PlasmaBlade versus 13% using
      PhotonBlade (P  =  0.0006). CONCLUSIONS: COAG resulted in more damage than CUT;
      this effect was greatest with the active edge, and with polyurethane or copolymer
      insulation. PhotonBlade was associated with less damage to leads than
      PlasmaBlade.

PMID- 30288749
TI  - Aging, the menopausal transition, and hormone replenishment therapy: retrieval of
      confidence and compliance.
AB  - The negative health consequences of age and the postmenopausal hypoestrogenic
      state and their clinical management are described in this paper. While some
      dysfunctional elements are irreversibly entrained, others can be modified by an
      updated menopausal hormone therapy (MHT) strategy reflecting revision and
      reassessment of the initial Women's Health Initiative (WHI) reports. However,
      until that positive outcome is realized, menopausal women and their healthcare
      providers must re-establish willingness to utilize these effective strategies.
      This reluctance is fueled by persistent mistaken application of WHI results that
      reflect the bundled risk and benefits of MHT in asymptomatic women aged 50-79
      (average age 63), as opposed to women in their 40s and 50s who initiate therapy
      because of vasomotor symptoms. The absolute risk of adverse outcomes is much
      lower and the benefits dramatically higher in these younger women. In addition,
      newer FDA-approved formulations, lower dosage regimens, and transdermal delivery
      methodologies offer wider choice of approaches and promise even greater safety.
      The positive and negative lessons of the WHI have been learned and can be applied
      effectively.

PMID- 30288750
TI  - Albugo candida race diversity, ploidy and host-associated microbes revealed using
      DNA sequence capture on diseased plants in the field.
AB  - Physiological races of the oomycete Albugo candida are biotrophic pathogens of
      diverse plant species, primarily the Brassicaceae, and cause infections that
      suppress host immunity to other pathogens. However, A. candida race diversity and
      the consequences of host immunosuppression are poorly understood in the field. We
      report a method that enables sequencing of DNA of plant pathogens and plant
      associated microbes directly from field samples (Pathogen Enrichment Sequencing:
      PenSeq). We apply this method to explore race diversity in A. candida and to
      detect A. candida-associated microbes in the field (91 A. candida-infected
      plants). We show with unprecedented resolution that each host plant species
      supports colonization by one of 17 distinct phylogenetic lineages, each with an
      unique repertoire of effector candidate alleles. These data reveal the crucial
      role of sexual and asexual reproduction, polyploidy and host domestication in A.
      candida specialization on distinct plant species. Our bait design also enabled
      phylogenetic assignment of DNA sequences from bacteria and fungi from plants in
      the field. This paper shows that targeted sequencing has a great potential for
      the study of pathogen populations while they are colonizing their hosts. This
      method could be applied to other microbes, especially to those that cannot be
      cultured.

PMID- 30288752
TI  - Micra implantation in a patient with transposition of great arteries.
AB  - We describe a 56-year-old male with transposition of the great arteries and
      Mustard repair, superior vena cava obstruction, atrial fibrillation, and
      progressive deterioration of his epicardial lead performance. We were successful
      in deploying of Micra (Medtronic, Minneapolis, MN, USA) at the septo-apical area
      of his nonsystemic ventricle in a stable position with satisfactory pacing and
      sensing thresholds.

PMID- 30288751
TI  - FoxO1 is a critical regulator of M2-like macrophage activation in allergic
      asthma.
AB  - BACKGROUND: The pathogenesis of asthma and airway obstruction is the result of an
      abnormal response to different environmental exposures. The scientific premise of
      our study was based on the finding that FoxO1 expression is increased in lung
      macrophages of mice after allergen exposure and human asthmatic patients.
      Macrophages are capable of switching from one functional phenotype to another,
      and it is important to understand the mechanisms involved in the transformation
      of macrophages and how their cellular function affects the peribronchial stromal
      microenvironment. METHODS: We employed a murine asthma model, in which mice were
      treated by intranasal insufflation with allergens for 2-8 weeks. We used both a
      pharmacologic approach using a highly specific FoxO1 inhibitor and genetic
      approaches using FoxO1 knockout mice (FoxO1fl/fl LysMcre). Cytokine level in
      biological fluids was measured by ELISA and the expression of encoding molecules
      by NanoString assay and qRT-PCR. RESULTS: We show that the levels of FoxO1 gene
      are significantly elevated in the airway macrophages of patients with mild asthma
      in response to subsegmental bronchial allergen challenge. Transcription factor
      FoxO1 regulates a pro-asthmatic phenotype of lung macrophages that is involved in
      the development and progression of chronic allergic airway disease. We have shown
      that inhibition of FoxO1 induced phenotypic conversion of lung macrophages and
      downregulates pro-asthmatic and pro-fibrotic gene expression by macrophages,
      which contribute to airway inflammation and airway remodeling in allergic asthma.
      CONCLUSION: Targeting FoxO1 with its downstream regulator IRF4 is a novel
      therapeutic target for controlling allergic inflammation and potentially
      reversing fibrotic airway remodeling.

PMID- 30288753
TI  - Biatrial volume, estimated using magnetic resonance imaging, predicts atrial
      fibrillation recurrence after ablation.
AB  - INTRODUCTION: The predictive value of left atrial volume (LAV) in atrial
      fibrillation (AF) is known, but the relationship of right atrial volume (RAV) and
      biatrial volume (BAV) with AF recurrence after pulmonary vein isolation (PVI) is
      not clear. Cardiac magnetic resonance (CMR) imaging allows us to more precisely
      quantify atrial volume. We investigated LAV, RAV, and BAV as predictors of AF
      recurrence following PVI in AF patients. METHODS AND RESULTS: We assessed 100 AF
      patients (age = 59.8 +/- 9.5 years, 74 males, 26 females) who underwent
      nonenhanced CMR before their first PVI. LAV and RAV were measured using CMR. All
      patients were in sinus rhythm during CMR. BAV was calculated as the sum of LAV
      and RAV. During the 8-month follow-up, AF recurrence occurred in 23 patients.
      LAV, RAV, and BAV were significantly greater in patients with AF recurrence than
      in those without (LAV, 103.7 +/- 25.8 vs 81.8 +/- 24.2 mL, P < 0.001; RAV, 109.4
      +/- 27.0 vs 82.2 +/- 19.6 mL, P < 0.001; BAV, 213.1 +/- 46.7 vs 164.1 +/- 38.7
      mL, P < 0.001). Multivariate logistic regression analysis revealed that increased
      LAV, RAV, and BAV were significantly correlated with AF recurrence. The area
      under the receiver operation characteristic curve for BAV showed the largest
      value compared to that of LAV or RAV alone. CONCLUSIONS: LAV, RAV, and BAV were
      independent predictors of AF recurrence after PVI. Quantifying BAV may
      additionally improve prognostic stratification compared with LAV or RAV.

PMID- 30288754
TI  - The regulatory module MdPUB29-MdbHLH3 connects ethylene biosynthesis with fruit
      quality in apple.
AB  - The plant hormone ethylene is critical for climacteric fruit ripening, while
      glucose and anthocyanins determine the fruit quality of climacteric fruits such
      as apple. Understanding the exact molecular mechanism for this process is
      important for elucidating the interconnection of ethylene and fruit quality.
      Overexpression of apple MdbHLH3 gene, an anthocyanin-related basic helix-loop
      helix transcription factor (bHLH TF) gene, promotes ethylene production, and
      transgenic apple plantlets and trees exhibit ethylene-related root developmental
      abnormalities, premature leaf senescence, and fruit ripening. Biochemical
      analyses demonstrate that MdbHLH3 binds to the promoters of three genes that are
      involved in ethylene biosynthesis, including MdACO1, MdACS1, and MdACS5A,
      activating their transcriptional expression, thereby promoting ethylene
      biosynthesis. High glucose-inhibited U-box-type E3 ubiquitin ligase MdPUB29, the
      ortholog of Arabidopsis AtPUB29 in apple, influences the expression of ethylene
      biosynthetic genes and ethylene production by direct ubiquitination of the
      MdbHLH3 protein. Our findings provide new insights into the ubiquitination of
      MdbHLH3 by glucose-inhibited ubiquitin E3 ligase MdPUB29 in the regulation of
      ethylene biosynthesis as well as indicate that the regulatory module MdPUB29
      MdbHLH3 connects ethylene biosynthesis with fruit quality in apple.

PMID- 30288755
TI  - Breakthrough percepts of famous faces.
AB  - Recently, we showed that presenting salient names (i.e., a participant's first
      name) on the fringe of awareness (in rapid serial visual presentation, RSVP)
      breaks through into awareness, resulting in the generation of a P3, which (if
      concealed information is presented) could be used to differentiate between
      deceivers and nondeceivers. The aim of the present study was to explore whether
      face stimuli can be used in an ERP-based RSVP paradigm to infer recognition of
      broadly familiar faces. To do this, we explored whether famous faces
      differentially break into awareness when presented in RSVP and, importantly,
      whether ERPs can be used to detect these breakthrough events on an individual
      basis. Our findings provide evidence that famous faces are differentially
      perceived and processed by participants' brains as compared to novel (or
      unfamiliar) faces. EEG data revealed large differences in brain responses between
      these conditions.

PMID- 30288756
TI  - Sonographic diagnosis of coexisting ectopic thyroid and fourth branchial cleft
      cyst.
AB  - Ectopic thyroid and fourth branchial cleft anomaly are rare congenital anomalies
      of the neck. This is a case report of the coexistence of these two rare
      congenital anomalies in a 1-year-old girl. She had ectopic lingual thyroid and
      asymptomatic abscess in the fourth branchial cleft cyst, which was found in
      ultrasonography carried out to evaluate congenital hypothyroidism. To the best of
      our knowledge, this is the first reported case of ectopic thyroid coexisting with
      fourth branchial cleft anomaly in the same patient.

PMID- 30288757
TI  - Differential effects of varied potassium and magnesium nutrition on production
      and partitioning of photoassimilates in potato plants.
AB  - Potassium (K) and magnesium (Mg) are essential macronutrients for plants; they
      play crucial roles for photoassimilate production and transport. The knowledge on
      both individual and interactive effects of K and Mg nutrition in potato (Solanum
      tuberosum L.) is limited. We aimed to determine whether K or Mg deficiencies
      impair photoassimilate production and transport, and consequently the development
      of tubers which are strong sink organs for photoassimilates. Potato plants were
      grown in pots using sand culture under various K and Mg supplies. Biomass
      production, CO2 net assimilation, leaf sugar concentrations and transcript levels
      of H+ /sucrose symporters in leaves were measured. Both K and Mg deficiencies
      reduced CO2 net assimilation and biomass production, with stronger reductions
      during K deficiency. Sugars accumulated in K- and, more importantly, in Mg
      deficient leaves. Low K or Mg supplies resulted in increased transcript levels of
      H+ /sucrose symporters, but the increase was less pronounced during Mg
      deficiency. The lower increase of transcript levels of H+ /sucrose symporters
      under Mg deficiency was probably caused by an impaired sucrose transport already
      at an earlier step, namely the efflux of sucrose from mesophyll cells into the
      apoplast. Thus, we assume that K and Mg deficiencies caused sugar accumulation in
      separated cell compartments of source leaves leading to a different impact on the
      gene expression of sucrose transport systems. Tuber sugar and starch
      concentrations, however, remained unaffected under the various treatments.
      Nevertheless, the total amount of tuber sugar and starch per plant decreased
      significantly during K and Mg deficiencies. This article is protected by
      copyright. All rights reserved.

PMID- 30288758
TI  - Intra-arc binary collimation algorithm for the optimization of stereotactic
      radiotherapy treatment of multiple metastases with multiple prescriptions.
AB  - PURPOSE: To design and implement a novel treatment planning algorithm based on a
      modification of dynamic conformal arc (DCA) therapy for the treatment of multiple
      cranial metastases with variable prescription doses. METHODS: A workflow was
      developed in which separate dose matrices were calculated for each target at each
      control point (i.e., the multileaf collimator (MLC) was fit conformally to that
      single target). A cost function was used to quantify the relative contributions
      of each dose matrix in the plan to the overall plan objectives. Simulated
      annealing was used to allow for the inclusion or exclusion of individual dose
      matrices at each control point. The exclusion of individual targets at a given
      control point is termed intra-arc binary collimation (iABC) in this work and is
      accomplished by closing the MLCs over the target for a duration specified by
      simulated annealing optimization. Dynamic collimator motions were employed to
      minimize the variation between the idealized dose matrices (i.e., perfectly
      collimated targets) and actual dose matrices (i.e., MLC apertures that include
      quantities of nontarget tissue due to the relative orientations of targets in the
      field). An additional simulated annealing optimization was performed to weight
      the relative contributions of dose at each control point [referred to as the
      monitor unit distribution (MUD)] to improve compliance with plan objectives. The
      algorithm was tested on seven previously treated multiple metastases patients and
      plans were compared to the clinically treated VMAT plans. RESULTS: Treatment
      plans generated with iABC used an average of 2716 (34%) fewer MU in the total
      plan than VMAT (P = 0.01). All normal tissue metrics for all plans and all
      patients were clinically acceptable. There were no statistically significant
      differences in any normal tissue dose metrics. Normalized prescription target
      coverage accuracy for all targets was 3% better on average for VMAT plans when
      compared to iABC (P = 0.07), and 14% better on average for iABC when compared to
      optimized DCA (P = 0.03). CONCLUSION: A novel method of aperture and dose
      distribution design has been developed to significantly increase the MU
      efficiency of single isocenter treatment of multiple metastases with variable
      prescription doses when compared to VMAT, and which improves target coverage
      accuracy significantly when compared to optimized DCA. By applying a DCA approach
      to subsets of targets across control points, a hybrid method of treatment
      delivery has been developed that combines the efficiency of dynamic conformal
      treatments and the dosimetric flexibility of VMAT.

PMID- 30288759
TI  - Hypoalbuminemia: Pathogenesis and Clinical Significance.
AB  - Hypoalbuminemia is associated with inflammation. Despite being addressed
      repeatedly in the literature, there is still confusion regarding its pathogenesis
      and clinical significance. Inflammation increases capillary permeability and
      escape of serum albumin, leading to expansion of interstitial space and
      increasing the distribution volume of albumin. The half-life of albumin has been
      shown to shorten, decreasing total albumin mass. These 2 factors lead to
      hypoalbuminemia despite increased fractional synthesis rates in plasma.
      Hypoalbuminemia, therefore, results from and reflects the inflammatory state,
      which interferes with adequate responses to events like surgery or chemotherapy,
      and is associated with poor quality of life and reduced longevity. Increasing or
      decreasing serum albumin levels are adequate indicators, respectively, of
      improvement or deterioration of the clinical state. In the interstitium, albumin
      acts as the main extracellular scavenger, antioxidative agent, and as supplier of
      amino acids for cell and matrix synthesis. Albumin infusion has not been shown to
      diminish fluid requirements, infection rates, and mortality in the intensive care
      unit, which may imply that there is no body deficit or that the quality of
      albumin "from the shelf" is unsuitable to play scavenging and antioxidative
      roles. Management of hypoalbuminaemia should be based on correcting the causes of
      ongoing inflammation rather than infusion of albumin. After the age of 30 years,
      muscle mass and function slowly decrease, but this loss is accelerated by
      comorbidity and associated with decreasing serum albumin levels. Nutrition
      support cannot fully prevent, but slows down, this chain of events, especially
      when combined with physical exercise.

PMID- 30288761
TI  - Zero-Balance Ultrafiltration of Priming Blood Attenuates Procalcitonin and
      Improves the Respiratory Function in Infants After Cardiopulmonary Bypass: A
      Randomized Controlled Trial.
AB  - Blood priming is needed for cardiopulmonary bypass (CPB) in neonates and infants
      to avoid exceeding hemodilution; however, transfusion-related inflammation
      affects post-CPB outcomes in infant open-heart surgery. Procalcitonin, a newly
      detected inflammatory moderator and a sensitive parameter for predicting
      pulmonary dysfunction secondary to CPB, rises after CPB. We hypothesized that the
      hemofiltration of priming blood before CPB might decrease inflammatory mediators
      in the blood and post-CPB inflammatory replications, thereby improving the
      respiratory function after CPB in infants. Sixty infants with a weight below 10
      kg were divided randomly into two equal groups of CPB with the zero-balance
      ultrafiltration (Z-BUF) of priming blood and CPB without it. The procalcitonin
      level was measured before anesthesia, after admission to the intensive care unit
      (ICU), and 24 h afterward. The respiratory index and pulmonary compliance were
      measured after anesthesia, at the end of CPB, and 2 h after admission to the ICU.
      Additionally, time to extubation was recorded. The Z-BUF of priming blood
      maintained electrolytes within a physiologic level, and procalcitonin had a
      slighter rise in the Z-BUF Group at 24 h after admission to the ICU (P = 0.05).
      The respiratory index was decreased in the Z-BUF Group, but the difference with
      the control group did not reach statistical significance (P > 0.05). The change
      in pulmonary compliance was significantly increased in the cyanotic patients in
      the intervention group, but there was no significant difference between the two
      groups. The time to extubation and the ICU stay were shorter in the Z-BUF Group
      (P < 0.05). A positive correlation was found between the peak procalcitonin
      concentration and the time to extubation directly and pulmonary compliance
      reversely. These results suggest that the Z-BUF of priming blood may have some
      beneficial clinical effects such as improved respiratory function and attenuated
      procalcitonin.

PMID- 30288760
TI  - ZmMADS69 functions as a flowering activator through the ZmRap2.7-ZCN8 regulatory
      module and contributes to maize flowering time adaptation.
AB  - Flowering time is a major determinant of the local adaptation of plants. Although
      numerous loci affecting flowering time have been mapped in maize, their
      underlying molecular mechanisms and roles in adaptation remain largely unknown.
      Here, we report the identification and characterization of MADS-box transcription
      factor ZmMADS69 that functions as a flowering activator through the ZmRap2.7-ZCN8
      regulatory module and contributes to adaptation. We show that ZmMADS69 underlies
      a quantitative trait locus controlling the difference in flowering time between
      maize and its wild ancestor, teosinte. Maize ZmMADS69 allele is expressed at a
      higher level at floral transition and confers earlier flowering than the teosinte
      allele under long days and short days. Overexpression of ZmMADS69 causes early
      flowering, while a transposon insertion mutant of ZmMADS69 exhibits delayed
      flowering. ZmMADS69 shows pleiotropic effects for multiple traits of agronomic
      importance. ZmMADS69 functions upstream of the flowering repressor ZmRap2.7 to
      downregulate its expression, thereby relieving the repression of the florigen
      gene ZCN8 and causing early flowering. Population genetic analyses showed that
      ZmMADS69 was a target of selection and may have played an important role as maize
      spread from the tropics to temperate zones. Our findings provide important
      insights into the regulation and adaptation of flowering time.

PMID- 30288762
TI  - Recovery of missing data in partial geometry PET scanners: Compensation in
      projection space vs image space.
AB  - PURPOSE: Robust and reliable reconstruction of images from noisy and incomplete
      projection data holds significant potential for proliferation of cost-effective
      medical imaging technologies. Since conventional reconstruction techniques can
      generate severe artifacts in the recovered images, a notable line of research
      constitutes development of appropriate algorithms to compensate for missing data
      and to reduce noise. In the present work, we investigate the effectiveness of
      state-of-the-art methodologies developed for image inpainting and noise reduction
      to preserve the quality of reconstructed images from undersampled PET data. We
      aimed to assess and ascertain whether missing data recovery is best performed in
      the projection space prior to reconstruction or adjoined with the reconstruction
      step in image space. METHODS: Different strategies for data recovery were
      investigated using realistic patient derived phantoms (brain and abdomen) in PET
      scanners with partial geometry (small and large gap structures). Specifically,
      gap filling strategies in projection space were compared with reconstruction
      based compensation in image space. The methods used for filling the gap structure
      in sinogram PET data include partial differential equation based techniques
      (PDE), total variation (TV) regularization, discrete cosine transform(DCT)-based
      penalized regression, and dictionary learning based inpainting (DLI). For
      compensation in image space, compressed sensing based image reconstruction
      methods were applied. These include the preconditioned alternating projection
      (PAPA) algorithm with first and higher order total variation (HOTV)
      regularization as well as dictionary learning based compressed sensing (DLCS). We
      additionally investigated the performance of the methods for recovery of missing
      data in the presence of simulated lesion. The impact of different noise levels in
      the undersampled sinograms on performance of the approaches were also evaluated.
      RESULTS: In our first study (brain imaging), DLI was shown to outperform other
      methods for small gap structure in terms of root mean square error (RMSE) and
      structural similarity (SSIM), though having relatively high computational cost.
      For large gap structure, HOTV-PAPA produces better results. In the second study
      (abdomen imaging), again the best performance belonged to DLI for small gap, and
      HOTV-PAPA for large gap. In our experiments for lesion simulation on patient
      brain phantom data, the best performance in term of contrast recovery coefficient
      (CRC) for small gap simulation belonged to DLI, while in the case of large gap
      simulation, HOTV-PAPA outperformed others. Our evaluation of the impact of noise
      on performance of approaches indicated that in case of low and medium noise
      levels, DLI still produces favorable results among inpainting approaches.
      However, for high noise levels, the performance of PDE4 (variant of PDE) and DLI
      are very competitive. CONCLUSIONS: Our results showed that estimation of missing
      data in projection space as a preprocessing step before reconstruction can
      improve the quality of recovered images especially for small gap structures.
      However, when large portions of data are missing, compressed sensing techniques
      adjoined with the reconstruction step in image space were the best strategy.

PMID- 30288763
TI  - New horizon for ventricular pacing.

PMID- 30288764
TI  - Juvenile pemphigus vulgaris manifesting as vegetating skin lesions.

PMID- 30288765
TI  - Power calculation of adjusted McNemar's test based on clustered data of varying
      cluster size.
AB  - McNemars test is often used to compare two proportions estimated from paired
      observations. When the observations are sampled in clusters, adjustment is needed
      to ensure that the size of McNemars test does not exceed the nominal level.
      Eliasziw and Donner (1991) developed an adjustment to McNemars test that involves
      first estimating the correlation between discordant pairs within a cluster, then
      using the estimate of the correlation to adjust the usual McNemar's test
      statistic. Gonen (2004) derived two approximations for calculating the power and
      sample size for the adjusted McNemar's test. He reported that the accuracy of the
      two approximations is compromised for large value of intracluster correlation and
      small value of proportion of discordant pairs; the error of the approximation can
      be higher than 10 per cent. In this paper, we extend his power formula, developed
      under fixed cluster size assumption, to accommodate the case where the cluster
      sizes are not constant. We show via simulations that the theoretical powers
      calculated from our proposed power formula are close to their empirical
      counterparts under a variety of settings. More significantly, in the case of
      fixed cluster size, our reduced power formula provides a more accurate power
      approximation than Gonen's power formula regardless of the values of intracluster
      correlation and the proportion of discordant pairs.

PMID- 30288766
TI  - The case against categorical risk estimates.
AB  - Risk estimates can be communicated in a variety of forms, including numeric and
      categorical formats. An example of the latter is "low/medium/high risk." The
      categorical format is preferred by judges and practitioners alike, and is
      mandated by the most commonly utilized forensic risk assessment instruments (the
      HCR-20 and the Static-99). This article argues against the practice of
      communicating risk in categorical terms on empirical and normative grounds.
      Empirically, there is no consensus about what level of risk corresponds to a
      particular category, such as "high risk." Moreover, recent studies indicate that
      categorizing an otherwise continuous risk estimate does not add incremental
      predictive validity to the risk estimate. Normatively, categorization obscures
      what is fundamentally a value judgment about the relative costs and benefits of
      correct (e.g., true positive) and incorrect (e.g., false positive) outcomes. Such
      a judgment is inherently non-scientific and invades the province of the jury.
      Indeed, categorical risk estimates are in principle no different than
      "dangerousness predictions," which are simply binary and which have been
      denounced by the field. The fact that alternative risk communication formats have
      limitations does not justify continuing the pervasive practice of communicating
      categorical risk estimates.

PMID- 30288767
TI  - Predictors of advanced fibrosis in non-cirrhotic non-alcoholic fatty liver
      disease in Germany.
AB  - BACKGROUND: Advanced fibrosis has been established as the most important
      predictor of overall mortality in patients with non-alcoholic fatty liver disease
      (NAFLD). In contrast to cirrhosis, advanced, non-cirrhotic NAFLD is difficult to
      identify and data from Germany are lacking. AIM: To identify clinical factors
      associated with advanced, non-cirrhotic fibrosis. METHODS: Patients were
      recruited in the prospectively enrolling European NAFLD Registry. Clinical
      characteristics and the performance of non-invasive surrogate scores compared
      with vibration-controlled transient elastography are reported. RESULTS: Two
      hundred and sixty-one patients with non-cirrhotic NAFLD on liver biopsy (mean age
      51 years, equal sex distribution) were included. The prevalence of stage 3
      fibrosis on liver biopsy was 15.7%. These patients were significantly older (57
      vs 50 years, P < 0.01), had a higher body mass index (32.3 vs 30.5, P < 0.05),
      and more frequent arterial hypertension (78% vs 50%, P = 0.001) and type 2
      diabetes (61% vs 24.1%, P < 0.001). On multivariate logistic regression, diabetes
      (OR = 4.68, 95% CI 2.17-10.10) and hypertension (OR = 2.91, 95% CI 1.12-7.18)
      were independent predictors of advanced fibrosis. Comedication included metformin
      in 50% and insulin in 33% of patients with diabetes. Despite the presence of
      cardiovascular risk factors, the use of statins was low. Liver stiffness
      measurement identified advanced fibrosis with an AUROC of 0.81 (95% CI 0.72
      0.91). The performance of NAFLD fibrosis score, Fibrosis-4, and AST to platelet
      ratio index were lower with AUCs of 0.74, 0.71, and 0.67, respectively.
      CONCLUSIONS: The prevalence of metabolic comorbidities in a German population
      with non-cirrhotic biopsy-proven NAFLD is high. While the examined scores exhibit
      an acceptable specificity, liver stiffness measurement appeared to be superior to
      blood-based non-invasive surrogate scores in ruling out advanced fibrosis.

PMID- 30288768
TI  - Dystrophic epidermolysis bullosa pruriginosa presenting with flagellate scarring
      lesions.

PMID- 30288769
TI  - Fungal bio-sorption potential of chromium in Norkrans liquid medium by shake
      flask technique.
AB  - In this study, the myco-reduction potential of fungi isolated from soil was
      ascertained by Norkrans shake flask experiment contaminated with chromium(VI).
      Fungal tolerance assay and induced tolerance training of the fungi were also
      carried out. Aspergillus niger, Penicillium, and Saccharomyces strains were
      isolated from the soil samples using culture based technique. Norkrans samples
      were collected and analyzed for Cr(VI) concentration using diphenylcarbazide
      spectrophotometric method. Penicillium strain was observed to be most effect at
      Cr(VI) concentrations of 16.1 and 8.1 mg L-1 since it was able to reduce Cr(VI)
      more than Saccharomyces strain and A. niger on day 20. Bio-sorption kinetics for
      this study was better described by pseudo second order model while Langmuir
      isotherm model fitted better to the equilibrium data. There was virtually steady
      increase in fungal growth for all the treatments through-out the experimental
      period. Significant negative correlation (p < 0.05) was observed between fungal
      growth and Cr(VI) reduction rate. The results from the induced tolerance training
      showed that Penicillium had the highest tolerance index (TI) values at 18, 20,
      and 25 mg L-1 concentrations of Cr(VI) compared to A. niger and Saccharomyces
      strain. These results demonstrated that these fungi have the potential to bio
      absorb Cr(VI) and if properly harnessed, could be used in place of conventional
      remediation technology to clean-up the Cr(VI) contaminant in the field.

PMID- 30288771
TI  - Review article: novel antivirals for hepatitis C
      sofosbuvir/velpatasvir/voxilaprevir, glecaprevir/pibrentasvir.
AB  - BACKGROUND: In 2017, the hepatitis C treatment regimens
      sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) and glecaprevir/pibrentasvir
      (G/P) received approval from the U.S. Food and Drug Administration. Although both
      SOF/VEL/VOX (NS5B polymerase inhibitor/NS5A inhibitor/NS3/4A protease inhibitor)
      and G/P (NS3/4A protease inhibitor/NS5A inhibitor) are pangenotypic regimens,
      they are indicated for distinct subsets of patients with hepatitis C. AIM: To
      compare and contrast available safety and efficacy data for SOF/VEL/VOX and G/P
      and outline their clinical utility. METHODS: For each of the regimens, this
      review outlines the indications, safety information, and the major clinical
      studies in which SOF/VEL/VOX and G/P were evaluated. RESULTS: SOF/VEL/VOX is
      positioned as a salvage regimen for patients previously treated with NS5A
      inhibitors and for genotype 1a- and 3-infected patients who had failed other
      sofosbuvir-containing regimens. G/P is the first pangenotypic regimen with an 8
      week duration for treatment-naive, non-cirrhotic patients, and it is indicated
      for patients with any genotype who have advanced kidney disease, including those
      on dialysis. CONCLUSION: The addition of SOF/VEL/VOX and G/P to existing
      hepatitis C treatment options will expand the number of patients who are eligible
      for and responsive to treatment, thus increasing the possibility of eliminating
      hepatitis C as a public health issue.

PMID- 30288770
TI  - Upgrading of by-product from beverage industry through solid-state fermentation
      with Candida utilis and Bacillus subtilis.
AB  - Yellow wine lees (YWL) are the main co-products in yellow wine industry with
      unbalanced amino acid (AA) profiles. Solid-state fermentation was employed in
      this study to upgrade the YWL for ruminant animals. A 3 * 3 orthogonal design was
      conducted to optimize the fermentation condition for optimal crude protein (CP)
      yield as follows: ratio of water to total solid medium at 50 : 100 (v/w),
      temperature of 30 degrees C, and ratio of Candida utilis to Bacillus subtilis at
      2 : 1. The contents of CP, peptides and AA of fermented products were 14.5, 40.9
      and 26.1% higher than those of the unfermented respectively. In particular, the
      essential AA were highly improved, especially for lysine and methionine. The
      fermentation increased the in vitro microbial protein synthesis with higher CP
      digestibility and dramatically enhanced the ability of scavenging free radicals
      of the YWL. It is concluded that the microbial pretreatment can greatly improve
      the nutritional value of YWL, making these materials more suitable as feeds for
      animals, including ruminants. SIGNIFICANCE AND IMPACT OF THE STUDY: Yellow wine
      lees (YWL) are the main co-products in yellow wine industry with unbalanced amino
      acid (AA) profiles and are not well utilized. A strain combination of Candida
      utilis and Bacillus subtilis was employed to upgrade YWL. Contents of crude
      protein and peptides of YWL were greatly increased by microbial fermentation.
      Essential AAs of YWL were highly improved after the solid-state fermentation and
      no negative impact was observed in in vitro digestibility. Fermented YWL may be a
      good feed source for ruminants.

PMID- 30288772
TI  - Novel and recurrent mutations in keratin 1 cause epidermolytic ichthyosis and
      palmoplantar keratoderma.
AB  - Mutations in keratin genes underlie a variety of epidermal and nonepidermal cell
      fragility disorders, and are the genetic basis of many inherited palmoplantar
      keratodermas (PPKs). Epidermolytic PPK (EPPK) is an autosomal dominant disorder
      that can be due to mutations in the keratin 1 gene, KRT1. Epidermolytic
      ichthyosis (EI), the major keratinopathic ichthyosis, is characterized by
      congenital erythroderma, blistering and erosions of the skin. Causative mutations
      in KRT1 and KRT10 have been described, with PPK being present primarily in
      association with the former. We report four unrelated cases (one with sporadic EI
      and three with autosomal dominant PPK), due to two novel and two recurrent KRT1
      mutations. Mutations in KRT1 are not only scattered throughout the keratin 1
      protein, as opposed to being clustered, but can result in a range of phenotypes
      as further confirmed by these mutations, giving a complex genotype/phenotype
      pattern.

PMID- 30288773
TI  - Non-specific labeling of macrophages with anti-cytokeratin 20 (SP33) in the
      evaluation of nodal micrometastasis from Merkel cell carcinoma: A pitfall for
      metastasis.

PMID- 30288774
TI  - Anxiety after coeliac disease diagnosis predicts mucosal healing: a population
      based study.
AB  - BACKGROUND: Coeliac disease has been linked to anxiety and depression. However,
      their association with mucosal healing is unknown. AIM: To examine the
      relationship between anxiety, depression and mucosal healing in coeliac disease.
      METHODS: Between 1969 and 2008, we collected data on all small intestinal
      biopsies with villous atrophy from Sweden's 28 pathology departments. We
      restricted our cohort to individuals with data on follow-up biopsy (either
      persistent villous atrophy [n = 3317] or mucosal healing [n = 4331]). Through Cox
      regression, we estimated hazard ratios (HRs) for anxiety or depression. RESULTS:
      During follow-up, 123 (2.8/1000 person-years) individuals with mucosal healing
      had developed anxiety, compared to 94 (2.1/1000 person-years) with persistent
      villous atrophy. Mucosal healing was hence associated with a higher risk of
      future anxiety (HR = 1.49; 95% CI = 1.12-1.96). Similarly, 167 (3.8/1000 person
      years) individuals with mucosal healing developed depression, compared to 148
      (3.3/1000 person-years) with persistent villous atrophy, corresponding to a HR of
      1.25 (95% CI = 0.99-1.59). Mucosal healing was more common in individuals with
      prior diagnoses of anxiety or depression before follow-up biopsy. Anxiety
      diagnosed between diagnostic and follow-up biopsy for coeliac disease was
      associated with an almost nine-fold increased chance of mucosal healing (odds
      ratio = 8.94; 95%CI = 2.03-39.27). CONCLUSION: Anxiety and depression are more
      common in coeliac disease patients with mucosal healing, both before and after
      follow-up biopsy, an association potentially mediated through more vigilant
      compliance with a gluten-free diet. This finding raises concern that achieving
      the goal of mucosal healing may come at a cost of an increased risk of mood
      disorders.

PMID- 30288775
TI  - Effects of consecutive monoculture of sweet potato on soil bacterial community as
      determined by pyrosequencing.
AB  - Soil bacteria play key roles in determining soil health and plant growth. In this
      study, four sweet potato fields that had been consecutively monocultured for 1,
      2, 3, and 4 years were used to investigate the effect of monoculture on soil
      physicochemical properties and soil bacterial communities. The results revealed
      that continuous cropping led to a significant decline in soil pH, soil organic
      carbon, and soil bacterial abundance. Miseq pyrosequencing analysis of 16S rRNA
      genes revealed that Proteobacteria and Bacteroidetes were the main phyla in the
      sweet potato monoculture soils, comprising up to 66.24% of the total sequences.
      The relative abundances of beneficial bacteria, including Actinobacteria,
      Gemmatimonadetes, Firmicutes, Xanthomonadaceae, Rhodospirillaceae, and
      Syntrophobacteraceae, as well as their subgroups at the genus and operational
      taxonomic unit (OTU) levels, decreased considerably as the number of continuous
      cropping years increased. In contrast, the number of potentially pathogenic
      bacteria, such as Acidobacteria, Sphingomonadaceae, and Pedobacter accumulated
      with increasing years. The results also showed the alterations to the bacterial
      community in the sweet potato monoculture soils were mainly driven by soil pH and
      soil organic matter. Overall, the decline in soil quality after successive sweet
      potato monoculture can be attributed to the imbalance in soil properties and soil
      microbes, including the decrease in soil pH and soil organic carbon, and the
      enrichment of pathogenic bacteria at the expense of plant-beneficial bacteria.

PMID- 30288776
TI  - Handgrip Strength, but Not 5-Meter Walk, Adds Value to a Clinical Nutrition
      Assessment.
AB  - BACKGROUND: Decreased physical functioning is associated with malnutrition and
      common in acute care patients; determining loss of function is often considered
      part of a comprehensive nutrition assessment. Handgrip strength (HGS) and 5-meter
      timed walk (5m) are functional measures used in a variety of settings. This
      analysis sought to determine which functional measure could be added to a
      hospital nutrition assessment, based on its feasibility and capacity to
      discriminate patient subgroups. METHODS: Eligible medical patients (no
      delirium/dementia, admitted from community; n = 1250), recruited from 5 hospitals
      that participated in a previous multisite action research study, provided data on
      demographics, HGS, 5m, nutrition status, perceived disability, and other
      characteristics. RESULTS: Significantly more patients (z = 17.39, P < .00001)
      were able to complete HGS than 5m (92% versus 43%, respectively). Median HGS was
      28.0 kg for men and 14.7 kg for women. Of patients who completed the 5m, mean
      completion time was 8.98 seconds (median, 6.79 seconds, SD = 6.59). 5m and HGS
      scores were significantly worse with patient-perceived disability (z = -9.56, t =
      10.69, respectively; P < .0001; 95% confidence interval [CI], [7.33, 10.63];
      [1.76, 3.18]). HGS was associated with nutrition status (t = 4.13, P < .001; 95%
      CI [2.02, 5.67]), although it showed poor validity as a single nutrition
      indicator. CONCLUSIONS: These data indicate that HGS is a more useful functional
      measure than 5m when added to a hospital nutrition assessment. Determination of
      HGS cutpoints to identify low strength in acute care patients will promote its
      use.

PMID- 30288777
TI  - Focal ultrasound strikes a new tune for targeted drug delivery.

PMID- 30288778
TI  - Meta-analysis of amantadine efficacy for improving preclinical research
      reliability.

PMID- 30288779
TI  - History and future challenges of the subthalamic nucleus as surgical target:
      Review article.
AB  - For many years the subthalamic nucleus had a poor reputation among neurosurgeons
      as a result of the acute movement disorders that develop after its lesion or
      manipulation through different surgical procedures. However, this nucleus is now
      considered a key structure in relation to parkinsonism, and it is currently one
      of the preferred therapeutic targets for Parkinson's disease. The implication of
      the subthalamic nucleus in the pathophysiology of chorea and in the parkinsonian
      state is thought to be related to its role in modulating the basal ganglia, a
      fundamental circuit in movement control. Indeed, recent findings have renewed
      interest in this anatomical structure. Accordingly, this review aims to present a
      history of the subthalamic nucleus, evolving from the classic surgical concepts
      associated with the avoidance of this structure, to our current understanding of
      its importance based on findings from more recent models. Future developments
      regarding the relationship of the subthalamic nucleus to neuroprotection are also
      discussed in this review. (c) 2018 International Parkinson and Movement Disorder
      Society.

PMID- 30288780
TI  - Importance of low diagnostic Accuracy for early Parkinson's disease.

PMID- 30288781
TI  - 123I-FP-CIT SPECT [(123) I-2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3
      fluoropropyl) nortropane single photon emission computed tomography] Imaging in a
      p.A53T alpha-synuclein Parkinson's disease cohort versus Parkinson's disease.
AB  - BACKGROUND: The p.A53T point mutation in the alpha-synuclein gene (SNCA) is a
      rare but highly relevant cause of autosomal dominant Parkinson's disease (PD).
      OBJECTIVES: The objective of this study was to assess striatal dopaminergic
      denervation in a cohort of symptomatic carriers of the p.A53T SNCA mutation as
      compared to PD patients. METHODS: Data from the Parkinson's Progression Markers
      Initiative database of 11 symptomatic p.A53T SNCA mutation carriers who underwent
      123I-FP-CIT SPECT [(123) I-2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3
      fluoropropyl) nortropane single photon emission computed tomography] imaging at
      our site were compared with those of 33 age-, sex-, and disease duration-matched
      PD patients. RESULTS: The p.A53T mutation carriers had significantly lower
      caudate nucleus binding ratio both contralaterally and ipsilaterally to the most
      affected side (P = .002 and P = .006) and a decreased contralateral
      caudate/putamen signal ratio (P = .007) as compared to PD. A similar degree of
      striatal asymmetry was observed in both subgroups. No correlation between scores
      in neuropsychological tests and caudate nucleus dopaminergic denervation could be
      demonstrated. CONCLUSIONS: PD patients harboring the p.A53T SNCA mutation show
      evidence of a more severe nigrostriatal denervation, especially evident in the
      caudate nucleus. The lack of significant differences in the putaminal binding
      ratios may reflect a floor effect or a true preferential targeting of the caudate
      terminals in p.A53T SNCA-associated PD. (c) 2018 International Parkinson and
      Movement Disorder Society.

PMID- 30288782
TI  - Radiosurgery as primary management for acromegaly.
AB  - OBJECTIVE: Transsphenoidal surgery (TSS) remains the recommended primary
      treatment for acromegaly. Long-term outcome data are not available for patients
      treated with gamma knife radiosurgery (STRS) as a primary treatment. DESIGN:
      Retrospective cohort study. DATA COLLECTION: notes review, laboratory results,
      general physician notes, patient questionnaire and death certification. PATIENTS:
      Twenty acromegaly patients underwent primary STRS at the National Centre for
      Radiosurgery, Sheffield, UK, between 1985 and 2015. MEASUREMENTS: Biochemical
      control (GH/IGF1), hypopituitarism, morbidity and mortality were all recorded.
      RESULTS: At 20 years of follow-up, control was seen in all on acromegaly-specific
      medication (n = 12) and 75% of those off medication (3/4). Time for 50% to
      achieve control on medication was 3 years, and 7.4 years off medication. Median
      marginal radiation dose was 27.5 Gy, and median follow-up was 166.5 months. 53%
      of patients developed new hypopituitarism at a median follow-up of 146 months,
      and the development of first onset of hypopituitarism occurred as late as 20
      years after treatment. With MRI planning, no other complications were noted.
      Three patients underwent subsequent TSS due to poor biochemical control. During
      follow-up, 7 patients died at a median age of 65 years. There were no STRS
      related deaths. CONCLUSION: This is the longest follow-up of patients who have
      undergone primary STRS for acromegaly. It shows low morbidity, but significant
      latency to biochemical control and new-onset hypopituitarism. This mandates very
      long-term follow-up for these patients. STRS has shown good long-term efficacy
      providing initial control can be afforded by optimal medical management. While
      TSS remains best practice, STRS offers an alternative for those in whom surgery
      is not an option.

PMID- 30288783
TI  - JMFT Annual Report 2017.

PMID- 30288784
TI  - Faust, J. (2017). Reunification family therapy: A treatment manual. Boston, MA:
      Hogrefe, 148 pp., $59.00.

PMID- 30288785
TI  - Johansson, T., & Andreasson, J. (2017). Fatherhood in transition: Masculinity,
      identity, and everyday life. London, UK: Palgrave Macmillan, 238 pp., $84.99.

PMID- 30288786
TI  - Oxidative stress in hemodialysis: Causative mechanisms, clinical implications,
      and possible therapeutic interventions.
AB  - Oxidative stress (OS) is the result of prooxidant molecules overwhelming the
      antioxidant defense mechanisms. Hemodialysis (HD) constitutes a state of elevated
      inflammation and OS, due to loss of antioxidants during dialysis and activation
      of white blood cells triggering production of reactive oxygen species. Dialysis
      vintage, dialysis methods, and type and condition of vascular access,
      biocompatibility of dialyzer membrane and dialysate, iron administration, and
      anemia all can play a role in aggravating OS, which in turn has been associated
      with increased morbidity and mortality. Oral or intravenous administration of
      antioxidants may detoxify the oxidative molecules and at least in part repair OS
      mediated tissue damage. Lifestyle interventions and optimization of a highly
      biocompatible HD procedure might ameliorate OS development in dialysis.

PMID- 30288787
TI  - Performance evaluation of five commercial assays for detection of acetaminophen.
AB  - BACKGROUND: To evaluate the analytical performance of five commercial
      acetaminophen assays and select the best method for routine use. METHODS:
      Imprecision, accuracy, linearity, and interferences of three enzymatic assays
      (Beckman Coulter AU Paracetamol, Abbott MULTIGENT Acetaminophen, and Sekisui
      Acetaminophen L3K) and two immunoassay-based assays (Beckman Coulter SYNCHRON
      ACTM (Acetaminophen) Reagent and Siemens SYVA Emit-tox Acetaminophen) were
      evaluated on a Beckman Coulter AU680 chemistry analyzer. Hook effect for
      immunoassay-based assays and recovery in ultrafiltrate for enzymatic methods were
      studied. RESULTS: Within-run and between-run imprecision of the enzymatic assays
      ranged 0.26%-0.82% and 0.53%-2.86%, respectively, while that for the immunoassay
      based methods ranged 0.96%-6.34% and 1.50%-11.33%, respectively. All assays
      except the SYNCHRON assay fell within the program analytical performance
      specifications (+/-20 umol/L or 10%) for external quality assurance (EQA)
      samples, with the highest positive bias (31.7%) observed in the SYNCHRON assay.
      Icteric interference was demonstrated most significantly in the Abbott assay (up
      to 88 MUmol/L positive bias in blank serum). The lipemic interference on the
      SYNCHRON was significant (up to 110% positive bias at level of 100 MUmol/L). The
      immunoassay-based methods were less susceptible to hemolytic interference, while
      the Abbott and AU assays were more susceptible to N-acetylcysteine interference.
      Both immunoassay-based methods showed no hook effect up to 18 000 MUmol/L.
      Ultrafiltration recoveries for enzymatic methods were satisfactory, ranging from
      80.0% +/- 5.1% to 89.5% +/- 3.0%. CONCLUSIONS: Proportional bias was observed in
      the SYNCHRON assay, while the Siemens and Sekisui assays were minimally affected
      by bilirubin interferences.

PMID- 30288788
TI  - Evaluation of the treatment costs and duration of topical treatments for multiple
      actinic keratosis based on the area of the cancerization field and not on the
      number of lesions.
AB  - BACKGROUND: The cost of topical treatments for actinic keratosis (AK) has
      historically been evaluated in relation to the number of lesions requiring
      treatment or simply by the price of a single tube/sachet of the drug used.
      OBJECTIVE: To demonstrate a new method of costing topical treatments in AK, which
      takes into account the actual cancerization area treated. METHODS: In order to
      evaluate the actual cost of each treatment, the official approval status of the
      drug was used to estimate the amount of cream needed per one cm2 . This value was
      then applied to the hypothetical cancerization area sizes to demonstrate the
      impact of the size treated on the actual cost of treatment. The price considered
      was the ex-factory price in Italy. RESULTS: Areas which could be treated with a
      single tube/sachet of Metvix(r) , Picato(r) , Aldara(r) , Solaraze(r) and
      Zyclara(r) were 200, 25, 25, 33.3 and 200 cm2 , respectively. For the treatment
      of smaller areas (<100 cm2 ), treatment with Metvix(r) was the most costly
      topical option in Italy. However, for the treatment of cancerization areas larger
      than 100 cm2 , Metvix(r) was the least expensive treatment option. Treatment with
      Metvix(r) was least long, requiring a single day of treatment for an area of up
      to 200 cm2 , compared with up to 224 days of treatment with Aldara(r) for the
      treatment of a similar size. CONCLUSION: Changing treatment costing strategy in
      the management of multiple AKs towards costing per cancerization area instead of
      costing per lesion is a much more accurate representation of the 'real world
      cost' for AK.

PMID- 30288789
TI  - Insulin resistance, mTOR and hidradenitis suppurativa.

PMID- 30288790
TI  - CAR-T cell therapy in melanoma: A future success story?
AB  - Chimeric antigen receptor (CAR)-T cells are one of the impressive recent success
      stories of anti-cancer immunotherapy. Especially in haematological malignancies,
      this treatment strategy has shown promising results leading to the recent
      approval of two CAR-T cell constructs targeting CD19 in the United States and the
      European Union. After the huge success in haematological cancers, the next step
      will be the evaluation of its efficacy in different solid tumors, which is
      currently investigated in preclinical as well as clinical settings. A commonly
      examined tumor model in the context of immunotherapy is melanoma, since it is
      known for its immunogenic features. However, the first results of CAR-T cell
      therapy in solid tumors did not reveal the same impressive outcomes that were
      observed in haematological malignancies, as engineered cells need to cope with
      several challenges. Obstacles include the lack of migration of CAR-T cells from
      blood vessels to the tumor site as well as the immunosuppressive tumor
      microenvironment within solid tumors. Another hurdle is posed by the
      identification of an ideal target antigen to avoid on-target/off-tumor
      toxicities. Regarding immune escape mechanisms, which can be developed by tumor
      cells to bypass immune recognition, the observation of antigen loss should also
      be considered. This article gives an overview of the challenges displayed in CAR
      T cell therapy for the use in solid tumors and discusses different new strategies
      and approaches that deal with these problems in order to improve CAR-T cell
      therapy, particularly for its use in melanoma.

PMID- 30288792
TI  - Author's response to Drs. Marasca et al. and Drs. De Vita and Melnik:
      hidradenitis suppurativa, insulin resistance and mTOR.

PMID- 30288791
TI  - Network analysis of symptoms in a Parkinson patient using experience sampling
      data: An n = 1 study.
AB  - BACKGROUND: Around 50% of Parkinson's disease patients experience motor
      fluctuations after long-term treatment with levodopa. These fluctuations may be
      accompanied by mood fluctuations. Routine cross-sectional assessments cannot
      capture the extent of these motor and mood fluctuations and their possible
      associations. Experience sampling techniques that use frequently repeated
      measurements of symptoms over time are able to capture such fluctuations. Based
      on such data, longitudinal associations between symptoms can be studied using
      network analysis. AIM: The purpose of this study is to identify longitudinal
      associations between motor symptoms and mood states in a patient with Parkinson's
      disease. METHODS: A 53-year-old man with Parkinson's disease and motor
      fluctuations collected experience sampling data during 34 consecutive days. A set
      of dependent variables included tremor, rigidity, balance problems, and "on/off"
      state, and the mood variables anxiety, cheerful, and "down." Independent
      variables were the same variables assessed at the preceding measurement.
      Regression coefficients were calculated and presented in a network graph.
      RESULTS: In this patient, anxiety and cheerfulness had a central position within
      the symptom network. Higher anxiety was prospectively associated with increased
      rigidity and tremor and with feeling "down." Cheerfulness was associated with
      less tremor. Balance problems were not influenced by cheerfulness nor anxiety,
      but increased balance problems were associated with reduced cheerfulness at the
      next assessment. Feeling "down" did not influence self-reported motor symptom
      severity at the next assessment. CONCLUSION: This n = 1 study shows that network
      analysis of experience sampling data may reveal longitudinal associations of self
      reported motor symptoms and mood states that may have relevance for treatment
      strategies. (c) 2018 International Parkinson and Movement Disorder Society.

PMID- 30288793
TI  - Formation and emission of hydrogen chloride in indoor air.
AB  - To improve our understanding of chlorine chemistry indoors, reactive chlorine
      species such as hydrogen chloride (HCl) must be analyzed using fast time-response
      measurement techniques. Although well studied outdoors, sources of HCl indoors
      are unknown. In this study, mixing ratios of gaseous HCl were measured at 0.5 Hz
      in the indoor environment using a cavity ring-down spectroscopy (CRDS)
      instrument. The CRDS measurement rate provides a major advance in observational
      capability compared to other established techniques. Measurements of HCl were
      performed during three types of household activities: (a) floor exposure to
      bleach, (b) chlorinated and nonchlorinated detergent use in household
      dishwashers, and (c) cooking events. Surface application of bleach resulted in a
      reproducible increase of 0.1 ppbv in the affected room. Emissions of HCl from
      automated dishwashers were observed only when chlorinated detergents were used,
      with additional HCl emitted during the drying cycle. Increased mixing ratios of
      HCl were also observed during meal preparation on an electric element stovetop.
      These observations of HCl derived from household activities indicate either
      direct emission or secondary production of HCl via chlorine atoms is possible.
      Calculations of photolysis rate constants of chlorine atom precursors provide
      evidence that photolysis may contribute to indoor HCl levels.

PMID- 30288794
TI  - Magnetic resonance-guided focused ultrasound thalamotomy for treatment of
      essential tremor: A 2-year outcome study.
AB  - BACKGROUND: Magnetic resonance-guided focused ultrasound is an emerging,
      minimally invasive thermoablation technique for medically refractory essential
      tremor. Beyond the initial year, data regarding efficacy and potential predictors
      of efficacy are still preliminary. OBJECTIVES: The objective of this study was to
      assess the outcome at 2 years and the association between lesion volume and
      outcome 1 year after treatment. METHODS: We reviewed data from 37 patients who
      underwent unilateral magnetic resonance-guided focused ultrasound thalamotomy,
      with primary outcome being dominant tremor subscore of the Clinical Rating Scale
      for Tremor. We used multivariable linear regression to model initial lesion
      volume with 1-year outcome, adjusting for other clinically relevant variables.
      RESULTS: Although we detected a trend in loss of clinical benefit within the
      first year, the dominant tremor score at 2 years continued to be significantly
      improved (43.4%, 95% confidence interval 27.8%-59.0%) from baseline. Secondarily,
      initial lesion volume is significantly associated with 1-year outcome.
      CONCLUSION: Our findings show that magnetic resonance-guided focused ultrasound
      thalamotomy results in sustained tremor reduction for medically refractory
      essential tremor even in the long term, and we highlight areas for improvement.

PMID- 30288795
TI  - First replication that biallelic variants in FITM2 cause a complex deafness
      dystonia syndrome.

PMID- 30288796
TI  - Acute localized exanthematous pustulosis due to metronidazole.

PMID- 30288798
TI  - What's wrong with mitochondria in Parkinson's disease?

PMID- 30288797
TI  - Developing Telemental Health Partnerships Between State Medical Schools and
      Federally Qualified Health Centers: Navigating the Regulatory Landscape and
      Policy Recommendations.
AB  - BACKGROUND: Federally Qualified Health Centers (FQHCs) deliver care to 26 million
      Americans living in underserved areas, but few offer telemental health (TMH)
      services. The social missions of FQHCs and publicly funded state medical schools
      create a compelling argument for the development of TMH partnerships. In this
      paper, we share our experience and recommendations from launching TMH
      partnerships between 12 rural FQHCs and 3 state medical schools. EXPERIENCE:
      There was consensus that medical school TMH providers should practice as part of
      the FQHC team to promote integration, enhance quality and safety, and ensure
      financial sustainability. For TMH providers to practice and bill as FQHC
      providers, the following issues must be addressed: (1) credentialing and
      privileging the TMH providers at the FQHC, (2) expanding FQHC Scope of Project to
      include telepsychiatry, (3) remote access to medical records, (4) insurance
      credentialing/paneling, billing, and supplemental payments, (5) contracting with
      the medical school, and (6) indemnity coverage for TMH. RECOMMENDATIONS: We make
      recommendations to both state medical schools and FQHCs about how to overcome
      existing barriers to TMH partnerships. We also make recommendations about changes
      to policy that would mitigate the impact of these barriers. Specifically, we make
      recommendations to the Centers for Medicare and Medicaid about insurance
      credentialing, facility fees, eligibility of TMH encounters for supplemental
      payments, and Medicare eligibility rules for TMH billing by FQHCs. We also make
      recommendations to the Health Resources and Services Administration about
      restrictions on adding telepsychiatry to the FQHCs' Scope of Project and the
      eligibility of TMH providers for indemnity coverage under the Federal Tort Claims
      Act.

PMID- 30288799
TI  - Position statement: topical calcineurin inhibitors in atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease in both
      adults and children. Whilst topical calcineurin inhibitors (TCIs), tacrolimus
      ointment and pimecrolimus cream, have proven efficacy for the treatment of AD, it
      is important to involve experts to obtain their opinion on its optimal treatment.
      OBJECTIVE: Using a modified Delphi approach, this project aimed to generate
      consensus amongst experts on the use of TCIs in the treatment of AD, with a focus
      on the differentiation between tacrolimus and pimecrolimus. METHODS: Six expert
      dermatologists from different European countries participated in this project
      based on their experience with AD and its treatment, which was evaluated by
      literature analysis and expert opinion. Consensus amongst the experts was
      generated using a modified Delphi approach, consisting of three distinct phases,
      during which a web meeting (June 2017), two online rounds of blinded Delphi
      voting (July-September 2017) and a face-to-face meeting (November 2017) were
      conducted. The consensus statements concerned two main topics: (i) Background of
      AD; and (ii) TCIs in AD. Hot topics in the treatment of AD not supported by meta
      analysis, clinical trials or large observational studies were also discussed
      based on clinical experience. RESULTS: In total, 25 consensus statements were
      defined and validated: eight statements on the general background of AD and 17
      statements on the use of TCIs in AD, including their mechanism of action and
      therapeutic indications in AD, efficacy in adult and paediatric AD patients,
      pharmacokinetics, incidence of adverse events and safety concerns. Hot topics on
      the use of TCIs for the treatment of AD included cream vs. ointment, dosages,
      TCIs contact allergy, burning sensation management, superinfection and
      vaccination concerns. CONCLUSION: Topical calcineurin inhibitors are a suitable
      therapy for AD, and selection of the specific TCI should be based on factors
      which differentiate tacrolimus from pimecrolimus.

PMID- 30288800
TI  - A Porous Cobalt Tetraphosphonate Metal-Organic Framework: Accurate Structure and
      Guest Molecule Location Determined by Continuous-Rotation Electron Diffraction.
AB  - Single-crystal electron diffraction has shown to be powerful for structure
      determination of nano- and submicron-sized crystals that are too small to be
      studied by single-crystal X-ray diffraction. However, it has been very
      challenging to obtain high quality electron diffraction data from beam sensitive
      crystals such as metal-organic frameworks (MOFs). It is even more difficult to
      locate guest species in the pores of MOF crystals. Here, we present synthesis of
      a novel porous cobalt MOF with 1D channels, [Co2 (Ni-H4 TPPP)]?2 DABCO?6 H2 O,
      (denoted Co-CAU-36; DABCO=1,4-diazabicyclo[2.2.2]octane), and its structure
      determination using continuous rotation electron diffraction (cRED) data. By
      combining a fast hybrid electron detector with low sample temperature (96 K),
      high resolution (0.83-1.00 A) cRED data could be obtained from eight Co-CAU-36
      crystals. Independent structure determinations were conducted using each of the
      eight cRED datasets. We show that all atoms in the MOF framework could be
      located. More importantly, we demonstrate for the first time that organic
      molecules in the pores, which were previously difficult to find, could be located
      using the cRED data. A comparison of eight independent structure determinations
      using different datasets shows that structural models differ only on average by
      0.03(2) A for the framework atoms and 0.10(6) and 0.16(12) A for DABCO and water
      molecules, respectively.

PMID- 30288801
TI  - Recent Development of Imide-Functionalized Polymer Semiconductors.
AB  - Imide-functionalized pi-conjugated polymer semiconductors have received great
      deal of interests owing to their unique physicochemical properties and
      optoelectronic characteristics, including excellent solubility, highly planar
      backbones, widely tunable bandgaps and energy levels of frontier molecular
      orbitals, and good film morphology. The organic electronics community has
      witnessed rapid expansion of materials library and remarkable improvement of
      device performance recently. This review summarizes the development of imide
      functionalized polymer semiconductors as well as their device performance in
      organic thin-film transistors and polymer solar cells, mainly achieved in the
      past three years. The materials mainly cover naphthalene diimide, perylene
      diimide, and bithiophene imide, and other type imide based polymer semiconductors
      are also discussed. The perspective offers our insights for developing new imide
      functionalized building blocks and polymer semiconductors with optimized
      optoelectronic properties. We hope that this review will generate more research
      interests in the community to realize further improved device performance by
      developing new imide-functionalized polymer semiconductors.

PMID- 30288802
TI  - Clinical phenotypes of hidradenitis suppurativa.

PMID- 30288803
TI  - Practices Surrounding Pain Management Among American Indians and Alaska Natives
      in Rural Southern California: An Exploratory Study.
AB  - OBJECTIVES: This exploratory study examined pain management practices among
      American Indians and Alaska Natives in the service area of a rural tribal clinic
      in Southern California. METHODS: Researchers invited 325 individuals to complete
      an anonymous survey in clinic waiting rooms and tribal gatherings. Analyses of
      the 295 eligible responses included calculating frequencies and conducting
      multiple logistic regressions and a Mantel-Haenszel analysis. RESULTS: Among
      respondents in this study, being male, younger, and having less education were
      strong predictors for riskier methods for managing pain. CONCLUSIONS:
      Understanding the methods individuals use to manage pain in a rural setting
      constitute a stepping-stone to develop strategies for reducing and preventing
      misuse and abuse of prescription medications and other drugs in rural American
      Indian and Alaska Native communities.

PMID- 30288804
TI  - Survival rates among Parkinson's disease patients who carry mutations in the
      LRRK2 and GBA genes.
AB  - BACKGROUND: The G2019S mutation in the LRRK2 gene generates a milder PD phenotype
      compared with GBA-PD; however, genetic based survival studies are lacking.
      OBJECTIVES: To compare mortality rates between LRRK2-PD, GBA-PD, and idiopathic
      PD patients (iPD). METHODS: Patients were screened for the G2019S mutation in the
      LRRK2 gene and the seven common GBA mutations among Ashkenazi Jews, classified as
      mild and severe (mGBA, sGBA). Motor symptoms onset and date of death were
      ascertained, with mortality rates calculated for each group of patients. RESULTS:
      Overall, 380 of 1,086 idiopathic PD patients, 49 of 159 LRRK2-PD, 56 of 148 mGBA
      PD, and 13 of 49 sGBA-PD participants died by the time of analysis. LRRK2-PD
      tended to have longer survival compared to idiopathic PD whereas GBA status did
      not affect mortality. Genetic status did not predict mortality in a multivariate
      analysis. CONCLUSION: Survival of patients with PD does not seem to be related to
      GBA status, whereas LRRK2 might confer higher survival rates.

PMID- 30288805
TI  - Why the relationship between level of alcohol-use and all-cause mortality cannot
      be addressed with meta-analyses of cohort studies.

PMID- 30288806
TI  - Three dimensional sonovaginography to assess posterior fornix and rectovaginal
      endometriosis - a new approach.
AB  - Deep infiltrating endometriosis (DIE) is characterized by foci of ectopic
      endometrial tissue, fibrosis and muscular hyperplasia that penetrate more than 5
      mm into affected pelvic organs. Endometriosis of the rectovaginal septum (RVS
      DIE) is the most severe form of DIE and has been described as endometriotic
      lesions that infiltrate both rectum and posterior vaginal fornix with possible
      extension to the rectovaginal septum.1 There are doubts regarding the definition
      and nomenclature involving this topography.2, 3 This article is protected by
      copyright. All rights reserved.

PMID- 30288807
TI  - Laparoscopic intraoperative ultrasound-guided excision with laparoscopic probe in
      fertility sparing surgery of borderline ovarian tumor recurrence.
AB  - A 30 year-old nulliparous woman, was referred to our center during her active
      surveillance program for previous serous borderline ovarian tumor (BOT). She
      underwent right salpingo-oophorectomy and then left ovarian cystectomy for
      primary and recurrent BOT in 2015 and 2016, respectively. At ultrasound
      examination, an unilocular-solid lesion of 16x12x16 mm in size was detected in
      the left ovary and it appeared as a mass with anechoic echogenicity, irregular
      contours, and presence of a papillary projection of 11x10x11 mm in size (Fig. 1 a
      and b). This article is protected by copyright. All rights reserved.

PMID- 30288808
TI  - Patterns of Telehealth Use Among Rural Medicaid Beneficiaries.
AB  - PURPOSE: Few studies have examined telehealth use among rural Medicaid
      beneficiaries. This study produced a descriptive overview of telehealth use in
      2011, including the prevalence of telehealth use among rural and urban Medicaid
      beneficiaries, characteristics of telehealth users, types of telehealth services
      provided, and diagnoses associated with telehealth use. METHODS: Using data from
      the 2011 Medicaid Analytic eXtract (MAX), we conducted bivariate analyses to test
      the associations between rurality and prevalence and patterns of telehealth use
      among Medicaid beneficiaries. FINDINGS: Rural Medicaid beneficiaries were more
      likely to use telehealth services than their urban counterparts, but absolute
      rates of telehealth use were low-0.26% of rural nondual Medicaid beneficiaries
      used telehealth in 2011. Psychotropic medication management was the most
      prevalent use of telehealth for both rural and urban Medicaid beneficiaries, but
      the proportion of users who accessed nonbehavioral health services through
      telehealth was significantly greater as rurality increased. Regardless of
      telehealth users' residence, mood disorders were the most common reason for
      obtaining telehealth services. As rurality increased, significantly higher
      proportions of telehealth users received services to address attention
      deficit/hyperactivity disorder (ADHD) and other behavioral health problems
      usually diagnosed in childhood. CONCLUSIONS: These findings provide a baseline
      for further policy-relevant investigations including examinations of changes in
      telehealth use rates in Medicaid since 2011. Reimbursement policies and unique
      rural service needs may account for the observed differences in rural-urban
      Medicaid telehealth use rates.

PMID- 30288809
TI  - Effects of health-related quality of life on health service utilisation in
      patients with colorectal neoplasms.
AB  - This study was to assess the impact of HRQOL on health service utilisation using
      four different count data models. The HRQOL was measured using the Short-Form Six
      Dimension instrument and the functional assessment of cancer therapy-colorectal
      whereas health service utilisation was measured by the number of monthly clinical
      consultations and the number of monthly hospitalisation. Different count data
      models (Poisson's regression, negative binomial regression, zero-inflated
      Poisson's regression and zero-inflated negative binomial regression) were used to
      assess the association between HRQOL and health service utilisation. A
      performance comparison was made between the models. Goodness-of-fit statistics
      (the Pearson's chi-squared test statistic, the Akaike and Bayesian information
      criteria) were used to determine the best-fitting model. The negative binomial
      model performed the best in assessing the association between HRQOL measures and
      health service utilisation in patients with colorectal neoplasm and thus
      recommended. Physical well-being of patients was negatively and significantly
      associated with the monthly rate of health service utilisation after controlling
      for patient demographics. Both physical and function well-beings of patients were
      negatively and significantly associated with the number of monthly
      hospitalisations. If the data for the condition-specific FACT-C are not
      available, SF-6D showed a very strong negative relationship with health service
      utilisation. Such models can be used to guide the allocation of clinical
      resources and funding for the care of colorectal cancer patients.

PMID- 30288810
TI  - Updates on the surface antigens of basophils: CD16 on basophils of patients with
      respiratory or insect venom allergy and the rejection of CD203c and CD63
      externalization decoupling by bisindolylmaleimides.
AB  - BACKGROUND: CD16 was previously suggested to be a new marker of basophils that is
      subject to downregulation by FcepsilonRI crosslinking. Certain compounds,
      including supraoptimal concentrations of the PKC inhibitors,
      bisindolylmaleimides, decouple the release of granules containing CD203c, CD63
      and histamine, and may thus help to identify the mechanisms related to the CD16
      externalization. OBJECTIVE: We hypothesized that CD16 is differentially expressed
      on the surface of basophils in patients with birch pollen or insect venom allergy
      and is subject to a regulation in response to allergens. We also employed CD203c
      and CD63 externalization decoupling by bisindolylmaleimides. METHODS: We
      performed a basophil activation test coupled with CD16 and histamine detection
      using cells isolated from patients with allergy to birch pollen or insect venom
      and negative controls. We employed two PKC inhibitors, bisindolylmaleimide II and
      Ro 31-8220 at their supraoptimal concentrations and, after difficulties
      reproducing previously published data, we analyzed the fluorescence of these
      inhibitors alone. We identified the CD16 isoforms by sequencing nested RT-PCR
      amplicons from flow cytometry sorted basophils and by cleaving the CD16b GPI
      anchor using a phospholipase C. RESULTS: We provide the first evidence that CD16a
      is expressed as a surface antigen on a small subpopulation of human basophils in
      patients with respiratory and insect venom allergy, and this antigen shows
      increased surface expression following allergen challenge or FcepsilonRI
      crosslinking. We rejected the apparent decoupling of the surface expression of
      basophil activation markers following the administration of bisindolylmaleimides.
      CONCLUSIONS & CLINICAL RELEVANCE: The inclusion of alphaCD16 in negative
      selection cocktails selects against a subset of basophils that are CD16+ or
      CD16dim . Using CD16dim basophils and unstained leucocytes, we show that previous
      studies with supraoptimal concentrations of bisindolylmaleimides are likely
      flawed and are not associated with the differential expression of CD203c and
      CD63.

PMID- 30288811
TI  - Kidney function during pregnancy: a systematic review and meta-analysis.
AB  - OBJECTIVES: To systematically review current literature on kidney function
      changes during pregnancy, to estimate the extent of adaptation over the course of
      both healthy physiological and hypertensive complicated singleton pregnancies and
      to determine healthy pregnancy reference values. METHODS: A meta-analysis was
      performed following a systematic review of current literature on kidney function
      during uncomplicated and complicated pregnancies. PubMed (NCBI) and Embase (Ovid)
      electronic databases were used for the literature search, which was performed
      from inception to July 2017. Studies were required to report a non-pregnant
      reference value of kidney function (either non-pregnant control group, pre
      pregnancy or postpartum measurement) and a pregnancy measurement during a
      predetermined and reported gestational age. Pooled mean differences between
      pregnancy measurements and reference value were calculated for predefined
      intervals of gestational age using a random-effects model described by
      DerSimonian and Laird. RESULTS: Twenty-nine studies were included with
      publication dates ranging from 1958 to 2016. As early as the first trimester,
      glomerular filtration rate (GFR) increases, up until 40 - 50% during physiologic
      pregnancy when compared to non-pregnant conditions. Inulin clearance was highest
      at 36 - 41 weeks with a 55.6% increase (? 53.7 ml/min CI 44.7 - 62.6), and
      creatinine clearance at 15 - 21 weeks with a 37.6% increase (?36.6 ml/min CI 26.2
      - 46.9). Serum creatinine values decrease was most prominent at 15-21 weeks with
      a 23.2 % decrease (? -0.19 mg/dl (CI -0.23 - -0.15) compared to non-pregnant
      conditions. The meta-regression analysis, containing eight studies on complicated
      pregnancies, showed a significant difference in for all kidney function
      parameters when comparing uncomplicated to complicated gestation. CONCLUSIONS: In
      healthy pregnancy, GFR accelerates as early as the first trimester and remains to
      function at a higher rate throughout gestation. In contrast, kidney function is
      decreased in hypertensive gestation. This article is protected by copyright. All
      rights reserved.

PMID- 30288813
TI  - The relationship between cannabis use and diabetes: Results from the National
      Epidemiologic Survey on Alcohol and Related Conditions III.
AB  - INTRODUCTION AND AIMS: The relationship between cannabis use and diabetes is
      puzzling. Although cannabis users versus non-users should theoretically have a
      higher likelihood of diabetes, epidemiological studies suggest otherwise.
      However, previous epidemiological studies have not considered the potential
      confounding effects of mental health disorders. As such, the relationship between
      cannabis use and diabetes was examined while accounting for a range of potential
      confounders, including mental health disorders. DESIGN AND METHODS: Data were
      obtained from the National Epidemiologic Survey on Alcohol and Related Conditions
      III. Chi-square tests were used to compare socio-demographics, lifestyle
      behaviours, physical health disorders and mental health disorders between
      diabetics and non-diabetics. Measures that exhibited statistical significance in
      these tests were subsequently included in multiple logistic regression analyses
      to quantify the relationships between lifetime and 12-month cannabis use and
      diabetes. RESULTS: Although there was a considerable attenuation in the magnitude
      of the odds ratios after adjustment for confounders, there was still a decreased
      likelihood of diabetes for cannabis users versus non-users. The corresponding
      odds ratios of diabetes were 0.81 (95% confidence interval 0.70, 0.94) and 0.51
      (95% confidence interval 0.41, 0.63) for lifetime and 12-month cannabis use,
      respectively. DISCUSSION AND CONCLUSIONS: A decreased likelihood of diabetes for
      cannabis users versus non-users was indicated after accounting for a range of
      potential confounders, including mental health disorders. Before the protective
      effects of cannabis use for diabetes can be suggested, further epidemiological
      studies are needed that incorporate prospective designs, as well as feature
      innovative exposure measurements and statistical analyses.

PMID- 30288812
TI  - Position Statement: Linear prurigo is a subtype of chronic prurigo.
AB  - BACKGROUND: Chronic prurigo (CPG) is a distinct disease characterized by chronic
      pruritus, history and/or signs of prolonged scratching and multiple pruriginous
      lesions. It may present with various clinical manifestations, including papules,
      nodules, plaques or umbilicated lesions. Some patients with chronic pruritus show
      pruriginous linear and scaring scratch lesions (LSSL) and it is unclear whether
      these lesions belong to the spectrum of CPG. OBJECTIVE: To achieve a consensus on
      the classification of pruriginous LSSL and establish criteria to differentiate
      them from similar appearing conditions of different nature. METHODS: Members of
      the Task Force Pruritus (TFP) of the European Academy of Dermatology and
      Venereology participated in the consensus conference, discussing representative
      clinical cases. Using the Delphi method, consensus was reached when >=75% of
      members agreed on a statement. RESULTS: Twenty-one members of the TFP with voting
      rights participated in the meeting. It was consented that LSSL occurs due to
      chronic pruritus and prolonged scratching, and share common pathophysiological
      mechanisms with CPG. LSSL were thus considered as belonging to the spectrum of
      CPG and the term 'linear prurigo' was chosen to describe this manifestation.
      CONCLUSION: Considering linear prurigo as belonging to the spectrum of CPG has
      important clinical implications, since both the diagnostic and therapeutic
      approach of these patients should be performed as recommended for CPG.
      Importantly, linear prurigo should be differentiated from self-inflicted skin
      lesions as factitious disorders or skin picking syndromes. In the latter,
      artificial manipulation rather than pruritus itself leads to the development of
      cutaneous lesions, which can show clinical similarities to linear prurigo.

PMID- 30288814
TI  - Prenatal diagnosis, natural history, postnatal treatment and outcome of 222 cases
      of spina bifida: experience of a tertiary center.

PMID- 30288815
TI  - mTORC1 at the crossroad of metabolism and immunity in hidradenitis suppurativa.

PMID- 30288816
TI  - Lon recognition of the replication initiator DnaA requires a bipartite degron.
AB  - DnaA initiates chromosome replication in bacteria. In Caulobacter crescentus, the
      Lon protease degrades DnaA to coordinate replication with nutrient availability
      and to halt the cell cycle during acute stress. Here, we characterize the
      mechanism of DnaA recognition by Lon. We find that the folded state of DnaA
      appears crucial for its degradation, in contrast to the well-known role of Lon in
      degrading misfolded proteins. We fail to identify a single degradation motif
      (degron) sufficient for DnaA degradation, rather we show that both the ATPase
      domain and a species-specific N-terminal motif are important for productive Lon
      degradation of full-length DnaA. Mutations in either of these determinants
      disrupt DnaA degradation in vitro and in vivo. However, analysis of truncation
      products reveals that appending other extensions to the ATPase domain is
      sufficient to trigger degradation, suggesting plasticity in Lon recognition. Our
      final working model is that Lon engages DnaA through at least two elements, one
      of which anchors DnaA to Lon and the other acting as an initiation site for
      degradation.

PMID- 30288817
TI  - Food-induced fatal anaphylaxis: From epidemiological data to general prevention
      strategies.
AB  - BACKGROUND: Anaphylaxis hospitalizations are increasing in many countries, in
      particular for medication and food triggers in young children. Food-related
      anaphylaxis remains an uncommon cause of death, but a significant proportion of
      these are preventable. AIM: To review published epidemiological data relating to
      food-induced anaphylaxis and potential risk factors of fatal and/or near-fatal
      anaphylaxis cases, in order to provide strategies to reduce the risk of severe
      adverse outcomes in food anaphylaxis. METHODS: We identified 32 published studies
      available in MEDLINE (1966-2017), EMBASE (1980-2017), CINAHL (1982-2017), using
      known terms and synonyms suggested by librarians and allergy specialists.
      RESULTS: Young adults with a history of asthma, previously known food allergy
      particularly to peanut/tree nuts are at higher risk of fatal anaphylaxis
      reactions. In some countries, cow's milk and seafood/fish are also becoming
      common triggers of fatal reactions. Delayed adrenaline injection is associated
      with fatal outcomes, but timely adrenaline alone may be insufficient. There is
      still a lack of evidence regarding the real impact of these risk factors and co
      factors (medications and/or alcohol consumption, physical activities, and mast
      cell disorders). CONCLUSIONS: General strategies should include optimization of
      the classification and coding for anaphylaxis (new ICD 11 anaphylaxis codes),
      dissemination of international recommendations on the treatment of anaphylaxis,
      improvement of the prevention in food and catering areas, and dissemination of
      specific policies for allergic children in schools. Implementation of these
      strategies will involve national and international support for ongoing local
      efforts in relationship with networks of centres of excellence to provide
      personalized management (which might include immunotherapy) for the most at-risk
      patients.

PMID- 30288818
TI  - The proof is in the bulb: glycerol influences key stages of lily development.
AB  - A bulb is a whole plant condensed into an underground organ. A geophyte's bulb
      comprises both food reserves and important developmental history that may affect
      its whole growth. In Easter lily (Lilium longiflorum), bulb size is associated
      with the plant's flowering pathway - vernalization or photoperiod - and also
      affects sprouting, flower quality and abortion rate. The aim of this study was to
      investigate the reasons for the major physiological differences between large and
      small bulbs. Lily bulbs start their development from secondary meristems along
      the stem, with large bulbs being heavier and bear more scales than small ones.
      Peeling the outer scales of a large bulb converts its physiological responses
      into those of a small bulb, implying that the physiological discrepancies in
      plants developing from large or small bulbs are mediated by factors inherent to
      the bulb. We therefore performed broad analyses of the metabolite composition in
      the scales of bulbs subjected to temperature regimes affecting further plant
      development. We found a striking association between the level of glycerol, a
      primary metabolite mostly synthesized in the outer scales, and a delay in
      sprouting and flowering time, and reduction in abortion rate. Exogenous glycerol
      application to the bulbs before planting corroborated these results. Moreover,
      transcriptome analyses showed that flowering-promoting gene expression was
      downregulated in the bulb after glycerol treatment, while potential flowering
      inhibitor as well as a dormancy-related gene expressions were upregulated. Based
      on these studies, we postulate that glycerol is a major factor influencing both
      vegetative and reproductive development in lily.

PMID- 30288819
TI  - PacBio full-length cDNA sequencing integrated with RNA-seq reads drastically
      improves the discovery of splicing transcripts in rice.
AB  - In eukaryotes, alternative splicing (AS) greatly expands the diversity of
      transcripts. However, it is challenging to accurately determine full-length
      splicing isoforms. Recently, more studies have taken advantage of Pacific
      Bioscience (PacBio) long-read sequencing to identify full-length transcripts.
      Nevertheless, the high error rate of PacBio reads seriously offsets the
      advantages of long reads, especially for accurately identifying splicing
      junctions. To best capitalize on the features of long reads, we used Illumina RNA
      seq reads to improve PacBio circular consensus sequence (CCS) quality and to
      validate splicing patterns in the rice transcriptome. We evaluated the impact of
      CCS accuracy on the number and the validation rate of splicing isoforms, and
      integrated a comprehensive pipeline of splicing transcripts analysis by Iso-Seq
      and RNA-seq (STAIR) to identify the full-length multi-exon isoforms in rice
      seedling transcriptome (Oryza sativa L. ssp. japonica). STAIR discovered 11 733
      full-length multi-exon isoforms, 6599 more than the SMRT Portal RS_IsoSeq
      pipeline did. Of these splicing isoforms identified, 4453 (37.9%) were missed in
      assembled transcripts from RNA-seq reads, and 5204 (44.4%), including 268 multi
      exon long non-coding RNAs (lncRNAs), were not reported in the MSU_osa1r7
      annotation. Some randomly selected unreported splicing junctions were verified by
      polymerase chain reaction (PCR) amplification. In addition, we investigated
      alternative polyadenylation (APA) events in transcripts and identified 829 major
      polyadenylation [poly(A)] site clusters (PACs). The analysis of splicing isoforms
      and APA events will facilitate the annotation of the rice genome and studies on
      the expression and polyadenylation of AS genes in different developmental stages
      or growth conditions of rice.

PMID- 30288820
TI  - Transcriptional effects of cadmium on iron homeostasis differ in calamine
      accessions of Noccaea caerulescens.
AB  - Calamine accessions of the zinc/cadmium/nickel hyperaccumulator, Noccaea
      caerulescens, exhibit striking variation in foliar cadmium accumulation in
      nature. The Ganges accession (GA) from Southern France displays foliar cadmium
      hyperaccumulation (>1000 MUg g-1 DW), whereas the accession La Calamine (LC) from
      Belgium, with similar local soil metal composition, does not (<100 MUg g-1 DW).
      All calamine accessions are cadmium hypertolerant. To find out the differences
      between LC and GA in their basic adaptation mechanisms, we bypassed the cadmium
      excluding phenotype of LC by exposing the plants to 50 MUm cadmium in
      hydroponics, achieving equal cadmium accumulation in the shoots. The iron content
      increased in the roots of both accessions. GA exhibited significant decreases in
      manganese and zinc contents in the roots and shoots, approaching those in LC.
      Altogether 702 genes responded differently to cadmium exposure between the
      accessions, 157 and 545 in the roots and shoots, respectively. Cadmium-exposed LC
      showed a stress response and had decreased levels of a wide range of
      photosynthesis-related transcripts. GA showed less changes, mainly exhibiting an
      iron deficiency-like response. This included increased expression of genes
      encoding five iron deficiency-regulated bHLH transcription factors, ferric
      reduction oxidase FRO2, iron transporters IRT1 and OPT3, and nicotianamine
      synthase NAS1, and decreased expression of genes encoding ferritins and NEET (a
      NEET family iron-sulfur protein), which is possibly involved in iron transfer,
      distribution and/or management. The function of the IRT1 gene in the accessions
      was compared. We conclude that the major difference between the two accessions is
      in the way they cope with iron under cadmium exposure.

PMID- 30288822
TI  - Erythropoietic protoporphyria: A rare cause of painful hands and feet.

PMID- 30288821
TI  - Early-life exposure to sibling modifies the relationship between CD14
      polymorphisms and allergic sensitization.
AB  - BACKGROUND: Markers of microbial exposure are thought to be associated with risk
      of allergic sensitization; however, the associations are inconsistent and may be
      related to gene-environment interactions. OBJECTIVE: To examine the relationship
      between polymorphisms in the CD14 gene and allergic sensitization and whether
      sibling exposure, as a marker of microbial exposure, modified this relationship.
      METHODS: We used data from the Tasmanian Longitudinal Health Study and the
      Melbourne Atopy Cohort Study. Two CD14 polymorphisms were genotyped. Allergic
      sensitization was defined by a positive response to a skin prick test. Sibling
      exposure was measured as cumulative exposure to siblings before age 6 months, 2
      and 4 years. Logistic regression and multi-level mixed-effects logistic
      regression were used to examine the associations. Effect estimates across the
      cohorts were pooled using random-effects meta-analysis. RESULTS: CD14 SNPs were
      not individually associated with allergic sensitization in either cohort. In
      TAHS, cumulative sibling exposure before age 6 months, 2 and 4 years was each
      associated with a reduced risk of allergic sensitization at age 45 years. A
      similar effect was observed in MACS. Meta-analysis across the two cohorts showed
      consistent evidence of an interaction between cumulative sibling exposure before
      6 months and the rs5744455-SNP (P = 0.001) but not with the rs2569190-SNP (P =
      0.60). The pooled meta-analysis showed that the odds of sensitization with
      increasing cumulative exposure to sibling before 6 months of age was 20.9%
      smaller in those with the rs5744455-C-allele than the T-allele (OR = 0.83 vs
      1.05, respectively). CONCLUSION AND CLINICAL RELEVANCE: Cumulative sibling
      exposure reduced the risk of sensitization from childhood to middle age in
      genetically susceptible individuals.

PMID- 30288823
TI  - The Baby Moves smartphone app for General Movements Assessment: Engagement
      amongst extremely preterm and term-born infants in a state-wide geographical
      study.
AB  - AIM: The Baby Moves smartphone application is designed for parents to video their
      infants' spontaneous movement for remote General Movements Assessment (GMA). We
      aimed to assess the engagement with Baby Moves amongst high- and low-risk
      infants' families and the socio-demographic variables related to engagement.
      METHODS: Families of extremely preterm (EP; <28 weeks' gestational age) or
      extremely low-birthweight (ELBW; <1000 g) infants and term-born controls from a
      state-wide geographical cohort study were asked to download Baby Moves. Baby
      Moves provided reminders and instructions to capture videos of their infants'
      general movements. Parents were surveyed about Baby Moves' usability. RESULTS:
      The parents of 451 infants (226 EP/ELBW; 225 control) were recruited; 416 (204
      EP/ELBW; 212 control) downloaded Baby Moves, and 346 (158 EP/ELBW; 188 control)
      returned at least one scorable video for remote GMA. Fewer EP/ELBW families
      submitted a scorable video than controls (70 vs. 83%, respectively; odds ratio
      (OR) 0.48, 95% confidence interval (CI) 0.3-0.79, P = 0.003), but the difference
      diminished when adjusted for socio-demographic variables (OR 1.09, 95% CI 0.59
      2.0, P = 0.79). Families who received government financial support (OR 0.28, 95%
      CI 0.1-0.78, P = 0.015), who spoke limited English at home (OR 0.39, 95% CI 0.22
      0.69, P = 0.001) or with lower maternal education (OR 0.38, 95% CI 0.21-0.68, P =
      0.001) were less likely to return a scorable video. Surveyed parents responded
      mostly positively to Baby Moves' usability. CONCLUSIONS: Most parents in this
      study successfully used Baby Moves to capture infant movements for remote GMA.
      Families of lower socio-demographic status used Baby Moves less.

PMID- 30288824
TI  - Cutaneous diphtheria in a returned traveller.

PMID- 30288825
TI  - Increased risk of morbidities and health-care utilisation in children born
      following preterm labour compared with full-term labour: A population-based
      study.
AB  - AIM: Recent evidence is emerging indicating long-term effects in infants born
      after an episode of preterm labour (PTL), even if birth is at term. This
      population-based study compared long-term rates of outcomes and health-care
      utilisation (HCU) in children born following spontaneous preterm labour,
      irrespective of gestational age at delivery or of an uncomplicated pregnancy
      (SPTLu), with children born following full-term labour (FTL), overall stratified
      by comorbidity status and assessed using a composite morbidity measure (CM).
      METHODS: Retrospective data on mother-neonate pairs were collected from a patient
      linked dataset from the Netherlands Perinatal Registry and the PHARMO Database
      Network. Children born between 2000 and 2010 were followed until 2012. RESULTS:
      Of pregnancies in 134 006 mother-neonate pairs, 122 894 (92%) pregnancies
      resulted in FTL, and 11 112 (8%) resulted in PTL. Of the PTL pregnancies, 6599
      (59%) were SPTLu. Mean follow-up after birth was 6.6-6.7 years. Children from
      SPTLu pregnancies were at increased risk of neurodevelopmental and respiratory
      conditions compared with those from FTL pregnancies. In children from SPTLu
      pregnancies, the presence of the CM was associated with an increased risk of
      respiratory conditions and failure to thrive. Post-natal hospitalisations
      (incidence rate (IR) per 100 patient-years: 18.1 vs. 11.7) and specialist
      referrals (IR per 1000 patient-years: 290.6 vs. 184.5) occurred significantly
      more frequently in children from SPTLu versus FTL pregnancies. CONCLUSION: The
      increased risk of morbidities and HCU in children born following SPTLu pregnancy
      in this population-based setting reinforces the need for safe interventions that
      can effectively halt labour and lead to an improvement in childhood outcomes.

PMID- 30288826
TI  - Unusual localized skin laxity in three sika deer.

PMID- 30288827
TI  - Staphylococcus aureus-derived extracellular vesicles induce monocyte recruitment
      by activating human dermal microvascular endothelial cells in vitro.
AB  - BACKGROUND: Atopic dermatitis (AD) represents the most common inflammatory skin
      disorder in children showing massive infiltration of immune cells. The
      colonization of AD-afflicted skin by Staphylococcus aureus and S. aureus-derived
      extracellular vesicles (SEVs) has been associated with AD pathogenesis; however,
      the molecular mechanism underlying SEV-mediated inflammatory responses remains
      unclear. OBJECTIVE: We investigated how SEVs can mediate inflammatory responses
      in AD pathogenesis by examining the effect of SEVs on human dermal microvascular
      endothelia cells (HDMECs). METHODS: HDMECs were treated with SEVs, and the
      expression of cell adhesion molecules or cytokines was assessed using RT-qPCR,
      Western blot or cytokine array analyses. The receptor for SEVs and related
      signalling molecules in HDMECs were addressed and verified via gene knockdown or
      inhibitor experiments. The recruitment assay of human THP-1 monocytic cells on
      HDMECs was performed after SEV treatment in the presence or absence of the
      verified receptor or signalling molecule. RESULTS: SEVs, but not other gram
      positive bacteria-derived extracellular vesicles, directly activated HDMECs by
      increasing the expression of cell adhesion molecules (E-selectin, VCAM1 and
      ICAM1) and that of IL-6, the inflammatory cytokine; consequently, they enhanced
      the recruitment of THP-1 monocytic cells to HDMECs. The SEV-induced HDMEC
      activation was dependent on Toll-like receptor 4 and the NF-kappaB signalling
      pathway, which was rapidly activated within 1 hour post-treatment and followed by
      an upregulation of cell adhesion molecules and IL-6 at later time-points.
      Moreover, SEV-mediated HDMEC responses were more rapid and intense than those
      induced by the same protein concentrations of S. aureus extracts. CONCLUSIONS &
      CLINICAL RELEVANCE: SEVs as proinflammatory factors could mediate immune cell
      infiltration in AD by efficiently inducing endothelial cell activation and
      monocyte recruitment, which may provide insights into alleviating the S. aureus
      mediated onset or progression of AD and its phenotypes.

PMID- 30288828
TI  - Application of Box-Behnken design for ultrasound-assisted extraction and
      recycling preparative HPLC for isolation of anthraquinones from Cassia singueana.
AB  - INTRODUCTION: Cassia singueana Del. (Fabaceae) is a rare medicinal plant used in
      the traditional medicine preparations to treat various ailments. The root of C.
      singueana is a rich source of anthraquinones that possess anticancer,
      antibacterial and antifungal properties. OBJECTIVE: The objective of this study
      was to develop an ultrasound-assisted extraction (UAE) method for achieving a
      high extraction yield of anthraquinones using the response surface methodology
      (RSM), Box-Behnken design (BBD), and a recycling preparative high-performance
      liquid chromatography (HPLC) protocol for isolation of anthraquinones from C.
      singueana. METHODOLOGY: Optimisation of UAE was performed using the Box-Behnken
      experimental design. Recycling preparative HPLC was employed to isolate
      anthraquinones from the root extract of C. singueana. RESULTS: The BBD was well
      described by a quadratic polynomial model (R2  = 0.9751). The predicted optimal
      UAE conditions for a high extraction yield were obtained at: extraction time
      25.00 min, temperature 50 degrees C and solvent-sample ratio of 10 mL/g. Under
      the predicted conditions, the experimental value (1.65 +/- 0.07%) closely agreed
      to the predicted yield (1.64%). The obtained crude extract of C. singueana root
      was subsequently purified to afford eight anthraquinones. CONCLUSION: The
      extraction protocol described here is suitable for large-scale extraction of
      anthraquinones from plant extracts.

PMID- 30288829
TI  - Severe anaemia with reticulocytopenia: When watchful waiting is the best
      attitude.

PMID- 30288831
TI  - Facing somatic symptom disorder in the emergency department.
AB  - Somatic symptom disorder is a condition in which a patient's subjective report of
      physical symptoms is associated with distress; disruption of day-to-day
      functioning; or disproportionate thoughts, feelings and behaviours regarding the
      symptoms, whether or not they are associated with an identified medical
      condition. While somatic symptom disorder affects a considerable proportion of
      children and adolescents presenting to the emergency department (ED), it has not
      been well investigated in the ED literature, nor is there much formal training
      in, or guidelines for, how to care for affected patients in the ED. The aim of
      this paper is to highlight the historical clues commonly reported by these
      patients in order to try to help the emergency physicians recognise patients
      affected by a somatic symptom disorder. Adolescent age, the presence of daily
      subjective symptoms presenting daily for weeks or months, a long medical history
      record, an extensive diagnostic workup and, most of all, disproportionate
      functional impairment related to the symptoms are all features strongly
      suggestive of this disorder. Emergency physicians should become used to taking
      advantage of these clues to formulate a positive diagnosis of somatic symptom
      disorder according to the most recent diagnostic criteria. Emergency physicians
      have the unique opportunity to contribute to the correct diagnosis and treatment
      of these patients and to have a positive impact on their prognosis.

PMID- 30288830
TI  - Targeted ablation of specific electrogram patterns in low-voltage areas after
      pulmonary vein antral isolation in persistent atrial fibrillation: Termination to
      an organized rhythm reduces atrial fibrillation recurrence.
AB  - BACKGROUND: Ablation strategies have been developed to improve outcomes in
      patients with persistent atrial fibrillation (PsAF). However, the impact of
      atrial fibrillation (AF) termination on late AF recurrence is not well known. The
      aim of our study was to evaluate the impact of AF termination to atrial
      tachycardia (AT) or sinus rhythm (SR) during catheter ablation on late AF
      recurrence after the 3-month blanking period. METHODS AND RESULTS: We
      prospectively recruited 140 patients (mean age: 58.5 +/- 12.3 years old, 74.3%
      males) with uninterrupted PsAF of a mean duration of 3.7 months. Pulmonary vein
      antral isolation (PVAI) was the first ablation step, and if AF did not terminate
      (to SR or AT), we ablated low-voltage areas less than 0.4 mV with specific
      electrogram characteristics. We successfully converted AF to AT or SR in 56
      patients (40%) during PVAI (n = 24) or low-voltage ablation ( n = 32). The
      remaining 84 patients (60%) were electrically cardioverted to SR at the end of
      the procedure. One hundred patients (71.4%) maintained SR after a single
      procedure during a mean follow-up of 21.1 +/- 0.8 months. Of the 56 patients with
      AF termination, 46 (82.1%) had no recurrence, while in the group of 84 patients
      without AF termination, 54 patients (64.3%) remained in SR ( P < 0.02).
      CONCLUSION: Ablation of PVAI and specific electrograms in low-voltage areas less
      than 0.4 mV can lead to encouraging outcomes with a low recurrence rate as well
      as a lower need for redo procedures.

PMID- 30288832
TI  - ZFAS1: A novel vital oncogenic lncRNA in multiple human cancers.
AB  - Long noncoding RNAs (lncRNAs) are a class of noncoding, endogenous, single
      stranded RNAs longer than 200 nucleotides in length that are transcribed by RNA
      polymerase II. Mounting evidence has indicated that lncRNAs play key roles in
      several physiological and pathological processes by modifying gene expression at
      the transcriptional, posttranscriptional, epigenetic, and translation levels.
      Many reports have demonstrated that lncRNAs function as potential oncogene or
      tumour suppressors and thus play vital regulatory roles in tumourigenesis and
      tumour progression. ZNFX1 antisense RNA 1 (ZFAS1), a novel lncRNA transcribed in
      the antisense orientation of zinc finger NFX1-type containing 1(ZNFX1), was found
      to be increased in multiple cancers, such as gastric cancer and hepatocellular
      carcinoma, contributing to cancer development and progression. In the present
      review, we summarized recent progression on study of the functions and underlying
      molecular mechanisms of ZFAS1 related to occurrence and development of multiple
      cancers.

PMID- 30288833
TI  - Placental histopathology in preterm fetal growth restriction.
AB  - AIMS: Approximately 6-9% pregnancies are affected by fetal growth restriction
      (FGR). Placental alterations related to utero-placental insufficiency in FGR may
      induce placental vascular remodelling to the detriment of the fetus. The
      objective of this article was to study histopathological features of placentae in
      a cohort of preterm growth-restricted infants in comparison to a cohort of
      preterm appropriately grown infants. METHODS: In a cohort of 40 preterm infants
      of 28-32 weeks' gestation, placental histopathology was evaluated by a
      histopathologist, who was blinded to the identity of the grouping. Twenty infants
      had FGR, while 20 were appropriate for gestational age (AGA). Predefined
      histopathological characteristics were assessed based on the Amsterdam Placental
      Workshop Group Consensus Statement. RESULTS: The gestational age and birthweight
      of the FGR and AGA cohorts were 29.8 +/- 1.3 versus 30 +/- 0.9 weeks, P = 0.78
      and 923 +/- 168 versus 1403 +/- 237 g, <0.001, respectively. Maternal vascular
      malperfusion, accelerated villous maturation and fetal vascular malperfusion were
      features that were significantly more common in FGR placentae. CONCLUSION: Based
      on the results of the present study, specific placental histopathological changes
      may be present in FGR placentae, which may reflect the effects of utero-placental
      insufficiency.

PMID- 30288834
TI  - Needs of parents in a surgical neonatal intensive care unit.
AB  - AIM: While there is evidence of parental needs in the neonatal intensive care
      unit (NICU), parents of newborns admitted for general surgery are an under
      researched population. This study aimed to identify needs in parents of newborns
      admitted to the NICU for general surgery and whether health-care professionals
      meet these needs. METHODS: This was a prospective cohort study of 111 parents
      (57% mothers) of newborns admitted to a surgical NICU for general surgery in
      Australia from January 2014 to September 2015. Parents completed the Neonatal
      Family Needs Inventory (NFNI), comprising 56 items in five subscales (Support,
      Comfort, Information, Proximity, Assurance) at admission and discharge, as well
      as the Social Desirability Scale (SDS). Data were analysed using parametric and
      non-parametric techniques. RESULTS: At both admission and discharge, parents
      rated Assurance (M = 3.8, standard deviation (SD) = 0.24) needs as the most
      important, followed by Proximity (M = 3.6, SD = 0.32) and Information (M = 3.5,
      SD = 0.38). Mothers rated Assurance significantly more important than fathers (P
      < 0.02). Overall, parents' most important needs were having questions answered
      honestly (M = 3.96, SD = 0.19), seeing their infant frequently and knowing about
      the medical treatment (both M = 3.95, SD = 0.23). The 10 most important needs
      were met for more than 96% of parents, with no evidence of response bias.
      CONCLUSIONS: Reassurance is a priority need for parents in the surgical NICU.
      Mothers' and fathers' needs may be best met by practices based on family-centred,
      individualised care principles.

PMID- 30288835
TI  - Nurses' negative affective states, moral disengagement, and knowledge hiding: The
      moderating role of ethical leadership.
AB  - AIM: This study aims to investigate the influence of nurses' negative affective
      states on their knowledge-hiding behaviours through moral disengagement, and
      especially the moderating role of ethical leadership. BACKGROUND: Researchers
      have paid much attention to the harmfulness of knowledge hiding, yet the
      mechanisms of why and how nurses' negative affective states have an impact on
      their knowledge-hiding behaviours are less clear. METHOD: Two different
      questionnaire surveys were used in two different studies. In Study 1, a research
      design with three stages, including 323 nurses (64.47% response rate, 51.70%
      male) working in a hospital in Shanghai, China, was used. Study 2 involved 317
      nurses (63.40% response rate, 51.74% male) working in five hospitals in Shanghai,
      China. The two studies shared the same statistical method, in which hierarchical
      regression analyses, the Sobel test, and bootstrap estimates were used to test
      hypotheses. RESULTS: We found that (a) nurses' negative affective states were
      positively related to their knowledge-hiding behaviours; (b) moral disengagement
      partially mediated this relationship in Study 1, but fully mediated it in Study
      2; and (c) ethical leadership mitigated the indirect relationship between
      negative affective states and knowledge hiding via moral disengagement.
      CONCLUSION: Nurses with negative affective states are more likely to activate
      moral disengagement as a secondary cognitive process to make personal moral rules
      momentarily obscure, which, in turn, leads them to hide knowledge that is
      requested by other members. The above relationships will depend on the levels of
      ethical leadership. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should
      try to reduce nurses' knowledge-hiding behaviours by addressing nurses' negative
      affective states, decreasing nurses' moral disengagement, and performing ethical
      leadership behaviours.

PMID- 30288836
TI  - Detailed comparison between the wall thickness and voltages in chronic myocardial
      infarction.
AB  - BACKGROUND: The relationship between the local electrograms (EGMs) and wall
      thickness (WT) heterogeneity within infarct scars has not been thoroughly
      described. The relationship between WT and voltages and substrates for
      ventricular tachycardia (VT) was examined. METHODS: In 12 consecutive patients
      with myocardial infarction and VT, WT, defined by a multidetector computed
      tomography, and voltage were compared. In multicomponent EGMs, amplitudes of both
      far- and near-field components were manually measured, and the performance of the
      three-dimensional-mapping system automatic voltage measurement was assessed.
      RESULTS: Of 15 748 points acquired, 2677 points within 5 mm of the endocardial
      surface were analyzed. In total, 909 (34.0%) multicomponent EGMs were identified;
      785 (86.4%) and 883 (97.1%) were distributed in the WT less than 4 and 5 mm,
      respectively. Far-field EGM voltages increased linearly from 0.14 mV (0.08-0.28
      mV) in the WT: 0 to 1 mm to 0.70 mV (0.43-2.62 mV) in the WT: 4 to 5 mm (rho =
      0.430; P < 0.001), and a significant difference was demonstrated between any two
      WT-groups (P <= 0.001). In contrast, near-field EGM voltages varied from 0.27 mV
      (0.11-0.44 mV) in the WT: 0 to 1 mm to 0.29 mV (0.17-0.53 mV) in the WT: 4 to 5
      mm with a poorer correlation (rho = 0.062, P = 0.04). The proportion of points
      where the system automatically measured the voltage on near-field EGMs increased
      from less than 10% in areas of WT: 4 to 5 mm to 50% in areas less than 2 mm. Of
      21 VTs observed, seven hemodynamically stable VTs were mapped and terminated in
      WT: 1 to 4 mm area. CONCLUSIONS: Although far-field voltages gradually increase
      with the WT, near-field does not. The three-dimensional-mapping system
      preferentially annotates the near-field components in thinner areas (center of
      the scar) and the far-field component in thicker areas when building a voltage
      map. Critical sites of VT are distributed in WT: 1 to 4 mm areas.

PMID- 30288837
TI  - Nutritional assessment of resettled paediatric refugees in Western Australia.
AB  - AIM: Nutritional deprivation, inadequate diet and food insecurity are common
      refugee experiences. The growth and nutritional status of paediatric refugees
      following resettlement in developed countries and the related interplay with
      socio-economic factors remain less defined; this study aims to describe these
      features. METHODS: Standardised dietary, medical and socio-demographic health
      assessments of new refugee patients attending a multidisciplinary paediatric
      Refugee Health Service (RHS) in Western Australia between 2010 and 2015 were
      analysed. RESULTS: Demographic data from 1131 paediatric refugees are described
      (age 2 months to 17.8 years). The majority experienced socio-economic
      disadvantage, had limited parental education and required interpreters.
      Nutritional deficiencies were common but varied across ethnicities: iron
      deficiency (ID) (12.3%), anaemia (7.3%) and inadequate dairy intake (41.0%). A
      third of children (32.6%) did not consume meat. Infant breastfeeding was
      sustained (77.8%) in infants <12 months. Prolonged breastfeeding (44.9% aged 12
      24 months) was associated with an increased risk of ID (odds ratio 4.0, 95%
      confidence interval 1.4-11.6). Median body mass index increased significantly for
      those >24 months between referral and RHS assessment (median period 1.8 months).
      Overall, 27.1% required additional formal dietetic follow-up, with higher
      nutritional concerns in refugee children <24 months compared to older patients.
      CONCLUSIONS: Identification of frequent post-settlement nutritional concerns has
      been captured through structured multidisciplinary paediatric health screening.
      Specific screening for socio-economic influencing factors, including education,
      poverty and food insecurity, during refugee clinical assessments is recommended.
      Development of targeted, culturally appropriate parental education resources and
      interventions may improve management following resettlement. Longitudinal
      research assessing resettlement growth trajectories is required.

PMID- 30288838
TI  - Coronary artery injury related to catheter ablation of cardiac arrhythmias: A
      systematic review.
AB  - INTRODUCTION: Catheter ablation (CA) has emerged as the preferred modality of
      treatment for many cardiac arrhythmias. Anatomical sites of ablation are often
      located in close proximity to coronary arteries. However, the incidence of CA
      related coronary injury has not been well studied. We sought to systematically
      evaluate all cases of CA-related coronary injuries. METHODS AND RESULTS: A PubMed
      search was conducted from inception until May 1, 2017 using the keywords
      "coronary artery" and "ablation." We identified 2817 published articles of which
      43 articles met our inclusion criteria representing 61 cases of coronary artery
      injury attributed to CA procedures from 1992 to 2017. Posteroseptal accessory
      pathway ablation was associated with the highest incidence of coronary injury
      (35.6% of cases), followed by cavotricuspid isthmus-dependent flutter (19.3%).
      The right coronary artery was the site of injury in over two-thirds of all
      reported cases. Coronary injury was detected intraprocedurally in about half of
      the cases (43.1%), whereas it was a delayed presentation in the other half.
      Coronary intervention was performed in a third of all cases (32.7%). There were a
      total of three deaths attributed to coronary artery injury. CONCLUSIONS: Most
      (91.8%) coronary injuries are a result of anatomic proximity to the site of
      ablation. Awareness of the relation between coronary artery course and anatomical
      site of ablation could prevent myocardial damage and improve procedural safety.

PMID- 30288840
TI  - Intersession improvement and outcome in psychotherapy.
AB  - OBJECTIVE: Psychotherapy patients who experience large, stable symptomatic
      improvement between sessions are more likely than those without such sudden gains
      to benefit from treatment. However, there is limited empirical basis for the
      definition of sudden gains, and it is unclear how they may affect symptomatic
      change at other points in treatment. METHOD: In a psychotherapy training clinic,
      149 adults completed a distress measure at each session. For each criterion in
      the definition of sudden gains, we evaluated the prediction of outcome, possible
      moderating variables, local score instability, and multisession change before and
      after score shifts. RESULTS: Large intersession improvement did not lead to
      increased rate of change later in treatment, but it did predict outcome,
      regardless of whether nearby session scores were stable. Early improvement during
      the first five treatment sessions was an independent predictor of outcome. Large
      intersession improvement generally occurred in the context of local score
      instability. CONCLUSION: Sudden gains appear to predict outcome because of
      improvement inherent in the gains themselves. Early overall improvement predicts
      outcome almost as effectively as do sudden gains. There may be advantages to
      redefining sudden gains as large intersession improvement, regardless of local
      score stability.

PMID- 30288839
TI  - Enrolment in paediatric oncology early-phase clinical trials: The health-care
      professionals' perspective.
AB  - AIM: Approximately 20-30% of children/adolescents with cancer will not respond to
      standard therapies. These children are usually offered experimental treatment in
      the form of an early-phase clinical trial. We examined the perspectives of health
      care professionals (HCPs) regarding obtaining informed consent for early-phase
      trials in paediatric oncology. METHODS: We collected survey data from 87 HCPs
      working in paediatric cancer centres across Australia and New Zealand. RESULTS:
      HCPs were, on average, 44 years old (range = 25-74), with 15.8 years' experience
      in paediatric oncology (range = 1-40). Few HCPs (17.4%) received training for
      early-phase trial consent; however, most were willing to attend training (77.9%).
      HCPs (61.6%) reported that they informed families about early-phase trials
      without any attempt to influence their decision. However, 23.3% of HCPs reported
      that they informed families that their child would benefit. HCPs' main obstacle
      in obtaining consent was their perception of parents' eagerness to 'try anything'
      (52.3%). HCPs perceived that many parents misunderstood key clinical trials
      concepts, with 25.2% of HCPs believing that not being given clear information
      influenced parents' decisions. Physicians were more likely than social
      workers/nurses to inform families that other children will benefit from enrolment
      in the study. Social workers/nurses appeared to rate the chance of benefits for
      the patient higher than physicians. CONCLUSIONS: HCPs may experience difficulty
      conducting early-phase trial consultations and obtaining valid informed consent.
      Our study highlights the need for formal training for HCPs and additional patient
      education tools.

PMID- 30288842
TI  - Life events, coping styles, and psychological well-being in children living with
      parents who harmfully consume alcohol.
AB  - INTRODUCTION: Children living with parents who harmfully consume alcohol might
      experience more life events, in particular negative, than children living with
      parents who do not harmfully consume alcohol. They also primarily use less
      adaptive coping styles and often demonstrate lower resilience. No studies
      evaluated whether coping styles or psychological well-being might influence the
      risk of life events occurrence in children living with parents who harmfully
      consume alcohol. METHODS: Forty-five children living with parents who harmfully
      consume alcohol and 45 children living with parents who do not harmfully consume
      alcohol, matched for sex and age, were assessed via the Appendix Life Events of
      the Minnesota Multiphasic Personality Inventory-Adolescent, the Coping Inventory
      for Stressful Situations, and the Psychological Well-Being scales. RESULTS:
      Children living with parents who harmfully consume alcohol had more life events
      in the 6-month period before the assessment, mostly negative and neutral, and
      lower levels of psychological well-being than children living with parents who do
      not harmfully consume alcohol. The risk of having experienced at least one
      negative or neutral life event was higher in children living with parents who
      harmfully consume alcohol than in their peers and in those with lower
      psychological well-being. The risk of having had a positive life event was not
      related to parents' consumption of alcohol but to avoidant coping and low self
      acceptance behaviours. CONCLUSIONS: Children living with parents who harmfully
      consume alcohol need interventions aimed at improving psychological well-being to
      protect them from life events, especially from negative ones.

PMID- 30288841
TI  - Macroreentrant atrial tachycardia detouring the epicardium at the anterior wall
      of the left atrium.
AB  - A 79-year-old woman with a history of pulmonary vein isolation for persistent
      atrial fibrillation was admitted for recurrence of atrial tachycardia, with a
      tachycardia cycle length of 236 milliseconds. The ultra-high-resolution mapping
      system revealed that tachycardia circuit detouring the epicardium at the anterior
      wall scar and breaking through to the endocardium below the left atrial
      appendage. Radiofrequency energy was applied to this site, which successfully
      terminated the tachycardia. This case suggests that epicardial conduction could
      occur even at the left atrial anterior wall and identifies a variation in
      epicardial conduction around the left atrium, which could be a tachycardia
      circuit.

PMID- 30288843
TI  - Delayed cord clamping in term large-for-gestational age infants: A prospective
      randomised study.
AB  - AIM: To compare the post-natal effects of delayed cord clamping (DCC) and early
      cord clamping (ECC) in term large-for-gestational age (LGA) infants. METHODS:
      This prospective randomised study included 51 term LGA infants. The umbilical
      cords of these infants were clamped at 15 s in group 1 (ECC group (n = 26)) and
      at 60 s in group 2 (DCC group (n = 25)). Data for Apgar scores, cord blood, pH
      and lactate values, second haematocrit, 24th bilirubin levels, duration of
      hospital stay and admission to the neonatal intensive care unit (NICU) were
      recorded. RESULTS: The demographic characteristics of the infants in the study
      group were not significantly different. No statistically significant difference
      was observed in the post-natal haematocrit and bilirubin levels between the
      groups. Six infants (group 1, n = 3; group 2, n = 3) were diagnosed with
      polycythaemia (P = 0.79); however, these infants remained asymptomatic, and no
      treatment was required. One infant in each group developed hyperbilirubinemia,
      which required phototherapy (P = 1.00). The infant with hyperbilirubinemia in the
      DCC group presented with asymptomatic polycythaemia. Three neonates in the DCC
      group required admission to the NICU for transient tachypnoea. CONCLUSIONS: No
      significant increase in the rate of post-natal complications of DCC in term LGA
      infants was observed in the study. However, before recommending DCC on a routine
      basis, studies with a larger sample size and long-term follow-up are required to
      elucidate the risks and benefits of DCC in this group of infants.

PMID- 30288844
TI  - The biopsychosocial model of pain in the context of pediatric burn injuries.
AB  - BACKGROUND: Burns are a common and traumatic source of childhood injury in the
      United States. The treatment and recovery from burn injuries can be significantly
      painful and may lead to chronic or persistent pain for years following the
      initial incident. Further, burn injuries in youth have been found to increase the
      potential for significant psychosocial (e.g., anxiety, depression, PTSD) and
      physical (e.g., decreased mobility) impairment. Relatedly, the general experience
      and processing of pain in youth can also be associated with greater psychosocial
      (e.g., anxiety, depression) impairment and functional disability over time.
      However, the phenomenology and associated characteristics of the pain experience
      following burn injury and, in particular, the potential for combined impact on
      physical and psychosocial outcomes in youth with severe and/or prolonged pain and
      a history of burn injury is poorly understood. METHODS: A review of the
      literature was performed in the areas of burn injuries and outcomes associated
      with both acute and chronic pain with youth and adult populations. RESULTS: The
      current review highlights current gaps in the literature in important areas of
      function in youth with a history of burn injuries using the biopsychosocial model
      of pain. Future research and considerations for practice are also outlined.
      CONCLUSIONS: Gaining a greater understanding of the relationship between pain,
      physical impairment, and psychosocial functioning in these youth is significantly
      important in order to provide greater preventative and treatment-related
      intervention going forward. SIGNIFICANCE: Using a biopsychosocial framework, this
      review highlights the need for a greater understanding of pain processing and the
      long-term potential for persistent pain and pain-related impairment (e.g.,
      functional disability) in youth with a history of burn injuries.

PMID- 30288845
TI  - The temporal signature of self: Temporal measures of resting-state EEG predict
      self-consciousness.
AB  - The self is the core of our mental life. Previous investigations have
      demonstrated a strong neural overlap between self-related activity and resting
      state activity. This suggests that information about self-relatedness is encoded
      in our brain's spontaneous activity. The exact neuronal mechanisms of such "rest
      self containment," however, remain unclear. The present EEG study investigated
      temporal measures of resting state EEG to relate them to self-consciousness. This
      was obtained with the self-consciousness scale (SCS) which measures Private,
      Public, and Social dimensions of self. We demonstrate positive correlations
      between Private self-consciousness and three temporal measures of resting state
      activity: scale-free activity as indexed by the power-law exponent (PLE), the
      auto-correlation window (ACW), and modulation index (MI). Specifically, higher
      PLE, longer ACW, and stronger MI were related to higher degrees of Private self
      consciousness. Finally, conducting eLORETA for spatial tomography, we found
      significant correlation of Private self-consciousness with activity in cortical
      midline structures such as the perigenual anterior cingulate cortex and posterior
      cingulate cortex. These results were reinforced with a data-driven analysis; a
      machine learning algorithm accurately predicted an individual as having a "high"
      or "low" Private self-consciousness score based on these measures of the brain's
      spatiotemporal structure. In conclusion, our results demonstrate that Private
      self-consciousness is related to the temporal structure of resting state activity
      as featured by temporal nestedness (PLE), temporal continuity (ACW), and temporal
      integration (MI). Our results support the hypothesis that self-related
      information is temporally contained in the brain's resting state. "Rest-self
      containment" can thus be featured by a temporal signature.

PMID- 30288846
TI  - Efficacy and safety of motherwort injection add-on therapy to carboprost
      tromethamine for prevention of post-partum blood loss: A meta-analysis of
      randomized controlled trials.
AB  - Motherwort (YiMuCao), a traditional Chinese herb, has been shown beneficial
      effects for women's diseases. This meta-analysis aimed to evaluate the efficacy
      and safety of motherwort injection add-on therapy to carboprost tromethamine for
      prevention of post-partum blood loss. A systematic literature search was
      conducted in PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang from their
      inception to December 2017. Randomized controlled trials that determined the add
      on effects of motherwort injection to carboprost for prevention of post-partum
      blood loss were eligible. Pooled risk ratio (RR) and mean difference (MD) with
      95% confidence interval (CI) were used to summarize the effect sizes. Eight
      trials including 1276 pregnant women fulfilled the inclusion criteria.
      Prophylactic use of motherwort injection add-on therapy significantly reduced the
      post-partum 2 h (MD -127.5 mL; 95% CI -149.13 to -105.88) and 24 h (MD -146.85
      mL; 95% CI -179.77 to -113.94) blood loss and incidence of post-partum hemorrhage
      (RR 0.28; 95% CI 0.17-0.45) than carboprost. Moreover, adjunctive treatment with
      motherwort injection significantly decreased the length of the third stage of
      labor (MD -3.41 min; 95% CI -4.33 to -2.49) and duration of lochia (MD -7.13
      days; 95% CI -8.49 to -5.76). There was no statistical significant difference in
      the incidence of adverse events (RR 0.76; 95% CI 0.50-1.16). Prophylactic use of
      motherwort injection add-on therapy to carboprost tromethamine could reduce post
      partum blood loss. However, more well-designed trials are necessary to confirm
      the findings of this study due to the methodological flaws of the included
      trials.

PMID- 30288847
TI  - Musculoskeletal pain in adults born preterm: Evidence from two birth cohort
      studies.
AB  - BACKGROUND: Individuals born preterm are at risk of later developmental problems
      and long-term morbidities. There is conflicting evidence regarding
      musculoskeletal pain in young adulthood. We investigated the prevalence of self
      reported musculoskeletal pain in young adults born across the range of preterm
      birth compared with a term-born reference group. METHODS: From two Finnish birth
      cohorts, 184 individuals born early preterm (<34 weeks), 350 late preterm (34 to
      <37 weeks) and 641 at term completed a self-report questionnaire of
      musculoskeletal pain at mean age 24.1 (SD: 1.4) years. Group differences were
      examined by logistic regression models adjusting for sex, age and cohort (Model
      1), potential early life confounders (Model 2) and lifestyle factors related to
      physical (Model 3) and mental health (Model 4). RESULTS: The late preterm group
      had lower odds for reporting neck pain (0.73; 95% confidence interval (CI): 0.56
      0.96), which was further reduced when adjusting for early life confounders and
      lifestyle factors (Model 4). Odds for reporting peripheral pain were 0.69 (95%
      CI: 0.48-0.99, Model 4) in the early preterm group. The odds for reporting any
      pain, shoulder, low back or widespread pain did not differ significantly between
      groups, although odds for reporting widespread pain were 0.77 (95% CI: 0.58-1.03,
      Model 4) in the late preterm group. CONCLUSIONS: We did not find evidence of
      increased prevalence of musculoskeletal pain in adults born early or late
      preterm. In contrast, our results suggest that adults born preterm have a
      slightly lower risk of reporting musculoskeletal pain, also when we adjusted for
      lifestyle factors. SIGNIFICANCE: Young adults born preterm do not have increased
      rates of musculoskeletal pain. Our findings rather suggest that these rates may
      be slightly lower than among those born at term.

PMID- 30288848
TI  - Procedural findings and clinical outcome of second-generation cryoballoon
      ablation in patients with variant pulmonary vein anatomy.
AB  - INTRODUCTION: The procedural findings and clinical outcome of second-generation
      cryoballoon (CB2) ablation in patients with variant pulmonary vein (PV) anatomy
      have not been fully investigated. METHODS: A total of 424 consecutive patients
      who underwent PV isolation with CB2 were included. Computed tomographic (CT) scan
      was performed in all patients before the procedure. The study population was
      divided into common PV, accessory PV, and nonvariant PV groups according to the
      CT scan. Procedural findings and clinical outcome between the three groups were
      compared. RESULTS: Variant PV anatomy was observed in 118 of 424 (27.8%)
      patients. PV isolation was successfully achieved in all patients in three groups
      with low rates of need for touch-up ablation (P = 0.974). Total procedure time
      was longer in the accessory PV group compared with nonvariant PV group (53.7 +/-
      12.9 vs 49.5 +/- 8.8 minutes; P < 0.001). More number of applications per patient
      were required in accessory PV group compared with the nonvariant PV and common PV
      groups (7.5 +/- 2.1 vs 6.5 +/- 1.6, P < 0.001; 7.5 +/- 2.1 vs 6.8 +/- 1.4, P =
      0.027, respectively). No significant difference in phrenic nerve (PN) injury was
      observed between the three groups (P = 0.693). During mean follow-up duration of
      16.1 +/- 3.3 months, there was no significant difference in rates of atrial
      fibrillation (AF) recurrences in the three groups (13 of 43 common PV group, 21
      of 75 accessory PV group, and 80 of 306 nonvariant PV group, P = 0.178).
      CONCLUSION: Variant PV patterns are common in patients undergoing ablation for
      drug-resistant AF. CB2 ablation appears to be a reasonable strategy in the
      setting of the variant PV anatomy with a small increase in procedure time and the
      number of cryoapplications.

PMID- 30288849
TI  - Postablation cerebral embolisms in balloon-based atrial fibrillation ablation
      with periprocedural direct oral anticoagulants: A comparison between cryoballoon
      and HotBalloon ablation.
AB  - INTRODUCTION: This prospective observational study aimed to investigate the
      incidence of symptomatic and silent cerebral embolisms after balloon-based
      ablation of atrial fibrillation (AF) in patients receiving periprocedural
      anticoagulation with direct oral anticoagulants (DOACs), and compare that between
      cryoballoon and HotBalloon ablation (CBA and HBA). METHODS AND RESULTS: We
      enrolled 123 consecutive AF patients who underwent a balloon-based pulmonary vein
      isolation (PVI) and brain magnetic resonance (MR) imaging after the ablation
      procedure (CBA, n = 65; HBA, n = 58). The DOACs were continued in 62 patients
      throughout the periprocedural period and discontinued in 61 on the procedural
      day. Intravenous heparin was infused to maintain an activated clotting time of
      300 to 400 seconds during the procedure. No symptomatic embolisms occurred in
      this series. Silent cerebral ischemic lesions (SCILs) were observed on MR imaging
      in 22 patients (17.9%), and the incidence of SCILs did not significantly differ
      between the CBA and HBA groups (21.5 vs 13.8%; P = 0.263). According to a
      multivariate logistic regression analysis, an older age was an independent
      positive predictor of SCILs (odds ratio, 1.062; 95% CI, 1.001-1.126; P = 0.046),
      but neither the balloon catheter type nor periprocedural continuation or
      discontinuation of the DOACs were significant predictors. The incidence of major
      and minor bleeding complications was comparable between the CBA and HBA groups
      (1.5 vs 0%, P = 0.528; 7.7 vs 5.2%, P = 0.424). CONCLUSIONS: Both CBA and HBA of
      AF revealed a similar incidence of postablation cerebral embolisms. Elderly
      patients may be at a risk of SCILs after a balloon-based PVI with periprocedural
      DOAC treatment.

PMID- 30288850
TI  - Sensory disturbances induced by sensorimotor conflicts are higher in complex
      regional pain syndrome and fibromyalgia compared to arthritis and healthy people,
      and positively relate to pain intensity.
AB  - BACKGROUND: Sensorimotor conflicts are well known to induce sensory disturbances.
      However, explanations as to why patients with chronic pain are more sensitive to
      sensorimotor conflicts remain elusive. The main objectives of this study were (a)
      to assess and compare the sensory disturbances induced by sensorimotor conflict
      in complex regional pain syndrome (n = 38), fibromyalgia (n = 36), arthritis (n =
      34) as well as in healthy volunteers (HV) (n = 32); (b) to assess whether these
      disturbances were related to the intensity and duration of pain, or to other
      clinical variables assessed using questionnaires (abnormalities in sensory
      perception, depression and anxiety); and (c) to categorize different subgroups of
      conflict-induced sensory disturbances. METHODS: One hundred and forty
      participants performed in phase or anti-phase movements with their arms while
      viewing a reflection of one arm in a mirror (and the other arm obscured). They
      were asked to report changes in sensory disturbances using a questionnaire.
      RESULTS: First, results showed that patients with complex regional pain syndrome
      and fibromyalgia were more prone to report sensory disturbances than arthritis
      patients and HV in response to conflicts (small effect size). Second, conflict
      induced sensory disturbances were correlated with pain intensity (large effect
      size) and abnormalities in sensory perception (only in the CRPS group) but were
      not related to the duration of the disease or psychological factors. Finally, we
      identified two distinct subgroups of conflict-induced sensory disturbances.
      CONCLUSIONS: Our results suggest that pain lowers the threshold for the detection
      of sensorimotor conflicts, a phenomenon that could contribute to the maintenance
      of pain in clinical populations. SIGNIFICANCE: Individuals with complex regional
      pain syndrome and fibromyalgia were more sensitive to sensorimotor conflicts than
      arthritis patients and controls. Moreover, conflict-induced sensory disturbances
      were specific to higher pain intensity and higher sensory abnormalities in all
      groups, suggesting that pain lowers the threshold for the detection of
      sensorimotor conflicts.

PMID- 30288851
TI  - IRGM promotes glioma M2 macrophage polarization through p62/TRAF6/NF-kappaB
      pathway mediated IL-8 production.
AB  - Alternatively activated (M2) macrophage promotes glioma progression and immune
      escape as the most immunocyte in glioma microenvironment. Finding out the key
      protein regulating M2 macrophage polarization is necessary for improving
      treatment. Whether immunity related GTPase M (IRGM) is involved in glioma
      development and M2 macrophage polarization is unknown. IRGM and M2 macrophage
      marker CD206 expression were examined using immunohistochemistry among 35 glioma
      and 11 non-cancerous brain specimens. We found IRGM scores were positively
      correlated with CD206 scores in glioma specimens and monocyte proportion in blood
      samples. A172 glioma cells transfected with either IRGM knock-down lentivirus
      (Lenti-IRGM) or control lentivirus (Lenti-HK) were subcutaneously injected into
      nude mice. In vivo, xenografted glioma size of the Lenti-IRGM group was smaller
      and had weaker fluorescence signal than Lenti-HK control group.
      Immunofluorescence results showed that there was obviously decreased IRGM, CD206
      and IL-8 expression in the mice glioma of Lenti-IRGM group than Lenti-HK control
      group. In vitro, flow cytometry results showed that M2 polarization from THP-1
      cocultured with Lenti-IRGM glioma cells decreased in contrast to that with Lenti
      HK glioma cells; there were less interleukin-8 (IL-8) and macrophage inflammation
      protein 3-alpha (MIP-3alpha), but more interleukin-6 (IL-6) in the supernatant of
      Lenti-IRGM glioma cells than matched control. Western blot and immunofluorescence
      displayed that IRGM strongly promoted sequestosome-1 (p62/SQSTM1), necrosis
      factor receptor-activating factor 6 (TRAF6) expression and NF-kappaB
      transportation to the nucleus. Realtime PCR results demonstrated IRGM also
      promoted NF-kappaB downstream cytokines IL-8 and MIP-3alpha mRNA expression.
      These data suggested that IRGM could promote glioma development and M2 macrophage
      polarization by regulating p62/TRAF6/NF-kappaB pathway-mediated IL-8 production.

PMID- 30288852
TI  - Altered tactile localization and spatiotemporal integration in complex regional
      pain syndrome patients.
AB  - BACKGROUND: In complex regional pain syndrome (CRPS), altered perception of the
      affected hand and neglect-like symptoms of the affected body side are common
      features. In this study, we presented tactile stimuli to the affected hands in
      CRPS patients and matched healthy controls. METHODS: The participants' task was
      to point at the perceived positions of the stimuli using a tracking device. The
      spatial coordinates of the perceived positions were analysed for accuracy and
      consistency. We also presented patterns consisting of two stimuli at distinct
      positions with a delay of 100 ms. These patterns are known to induce
      spatiotemporal integration ("sensory saltation"). RESULTS: CRPS patients were
      less accurate and less consistent in the spatial perception of tactile stimuli on
      their hands. Furthermore, they showed increased spatiotemporal integration,
      although these effects were smaller than expected. These deficiencies were
      related to the clinically assessed intensity of recurrent pain episodes.
      Surprisingly, the intensity of clinically assessed ongoing pain was associated
      with increased precision. CONCLUSIONS: In line with earlier reports, our findings
      indicate that the representation of the affected hands in CRPS patients is less
      accurate than in healthy people, probably reflecting reorganization in
      somatosensory cortices. The exact relationships between these findings and other
      aspects of CRPS remain to be elucidated. SIGNIFICANCE: CRPS patients performed
      poorly in localizing positions on their affected hands via pointing and exhibited
      increased spatiotemporal integration. The presented method may prove useful in
      diagnostics as well as psychophysical and neurofunctional research on CRPS and
      other chronic pain disorders.

PMID- 30288853
TI  - Efficacy and Safety of Computed Tomography-Guided Pulsed Radiofrequency
      Modulation of Thoracic Dorsal Root Ganglion on Herpes Zoster Neuralgia.
AB  - OBJECTIVE: Pulsed radiofrequency (PRF) can relieve postherpetic neuralgia (PHN)
      caused by herpes zoster (HZ) infection. Nevertheless, its curative effect can
      vary and may be related to the duration of treatment period. The following study
      investigates the efficacy and safety of CT-guided PRF modulation on HZ neuralgia
      over different periods and different time points. MATERIALS AND METHODS: A total
      of 150 patients with HZ/PHN were enrolled at the Pain Department, Shengjing
      Hospital of China Medical University between January 2013 and December 2016.
      According to the course of disease, the patients were randomly divided into group
      A, which included patients with acute stage (n = 50; course <1 m); group B, which
      included patients with subacute stage (n = 50; 1 m <course <3 m); and group C,
      which included patients with chronic stage (n = 50; course >3 m). The PRF therapy
      was performed in all patients by targeting thoracic dorsal root ganglion (DRG).
      The visual analogue scale (VAS), SF-36, total effective rate of treatment, and
      dosage of antiepileptic analgesic drugs were observed at different time points,
      before and after the surgery. RESULTS: Compared to preoperative time, decreased
      VAS, improved SF-36, and the decreased dosage of antiepileptic analgesic drugs
      were observed at all time points, and in all groups after surgery (p < 0.05). In
      group A, pain relief lasted longer, and it further decreased over time. In
      addition, significantly lower VAS, higher SF-36, and lower dosage of
      antiepileptic analgesic drugs were found in group A compared to group B, and in
      group B compared to group C (all p < 0.05). Furthermore, the total effective
      rates in groups A, B, and C were 88, 72, and 52%, respectively. CONCLUSIONS: CT
      guided PRF targeting thoracic DRG for modulation of HZ neuralgia in different
      periods is safe and effective. It is recommended to perform early intervention
      therapy at the acute phase of HZ.

PMID- 30288854
TI  - Interesting case of dual tachycardia in a patient with surgical closure of atrial
      septal defect.
AB  - A 34-year-old gentleman, who had undergone pericardial patch closure of ostium
      secundum atrial septal defect (ASD) at 8 years of age, was evaluated for
      shortness of breath. Electrocardiogram revealed typical atrial flutter with
      varying atrioventricular conduction. Echocardiogram showed no residual ASD or
      pulmonary hypertension and good biventricular function. He was taken for an
      electrophysiological study with the intention of radiofrequency ablation of the
      typical flutter.

PMID- 30288855
TI  - Mesenchymal stem cells induced anti-inflammatory features in B cells from breast
      tumor draining lymph nodes.
AB  - The immune-modulatory effect of adipose-derived stem cells (ASCs) on B cells in
      cancer has not been well elucidated. Herein, the interaction between B cells and
      ASCs isolated from the breast fat of either normal (nASCs) or breast cancer women
      (cASCs) was investigated. B cells derived from breast tumor draining lymph nodes
      were co-cultured with nASCs or cASCs and B cells proliferation was assessed in
      direct and transwell assays. Moreover, B cells were co-cultured with cASCs, nASCs
      or mesenchymal stromal cells of the tumor tissue (TSCs) and B cell cytokine
      production was assessed using flow cytometery. cASCs or TSCs were co-cultured
      with either intact or B cell depleted lymphocytes and frequencies of CD25+ FoxP3+
      Tregs, IL-10+ or IFN-gamma+ CD4+ T cells were assessed. Results showed that co
      culture of B cells with ASCs in transwell chambers did not affect B cell
      proliferation. nASCs, however, was able to significantly reduce B cell
      proliferation in direct co-culture experiments (P = 0.004). The frequencies of IL
      10+ , TNF-alpha+ , IL-2+ , and IFN-gamma+ B cells were not significantly
      different in the co-cultures of B cells with ASCs or TSCs. But the TNF-alpha+ /
      IL-10+ B cells ratio decreased in all co-cultures, a reduction merely significant
      in B cell-cASCs co-culture (P = 0.01). The frequencies of CD4+ T cells subsets in
      either intact or B cell depleted lymphocytes did not undergo significant changes
      following co-culture with ASCs or TSCs. Therefore, ASCs is capable of inhibiting
      B cell proliferation in a contact dependent manner and shifting the cytokine
      profile of B cells toward an anti-inflammatory profile.

PMID- 30288856
TI  - Identification of incident pancreatic cancer in Ontario administrative health
      data: A validation study.
AB  - PURPOSE: To validate three approaches for identifying incident cases of
      pancreatic cancer in Ontario administrative claims data. METHODS: We created a
      cohort using Ontario (Canada) administrative health data from 2002 to 2012 and
      identified cases of pancreatic cancer with three approaches, using the Ontario
      Cancer Registry (OCR) as the reference standard. In the any diagnosis approach,
      cases were defined by primary or secondary diagnostic codes for pancreatic cancer
      in outpatient or inpatient records. In the any inpatient diagnosis approach,
      cases were defined using only diagnoses in hospital discharge abstracts. In the
      algorithm approach, cases were identified by an algorithm that combined the first
      two approaches. Comparing each approach to the OCR, we calculated the expected
      value and 95% confidence interval (CI) of the sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value (NPV). We also compared the
      event dates using each approach with those recorded in the OCR. RESULTS: Among a
      total of 12 060 837 patients in Ontario administrative health data sources, 13
      999 incident pancreatic cancer cases were identified in the OCR. Sensitivity
      ranged from 72.5% (algorithm) to 97.5% (any diagnosis), and PPV ranged from 38.4%
      (any diagnosis) to 78.9% (any inpatient diagnosis). Specificity and NPV were
      ~100% for all approaches. The median absolute difference in cancer event date
      ranged 0 to 15 days. The any inpatient diagnosis method had the highest PPV
      (78.9%; 95% CI: 78.2-79.5%) and moderate sensitivity (86.6%; 95% CI: 86.0-87.2%).
      CONCLUSION: Inpatient diagnoses of pancreatic cancer in Ontario administrative
      heath data are suitable for pancreatic cancer case identification.

PMID- 30288857
TI  - Reply to the letter to editor by Zeki Gokhan Surmeli, M.D.

PMID- 30288859
TI  - Herniation of the amniotic sac through congenital uterine defect confirmed during
      operation: A case report.
AB  - Herniation of the amniotic sac into the peritoneal cavity or bladder is a rare
      but serious condition during pregnancy, which has not been reported in pored
      congenital uterine anomaly. Here, we report a rare case to draw obstetricians'
      attention to the atypical uterine rupture. A primigravida at 35 weeks of
      gestation was admitted for upper abdominal pain. A primary diagnosis of uterine
      rupture was made after finding the amniotic sac herniation through obstetric
      ultrasound. Exploration during emergent cesarean section revealed symmetrical
      pored defect on the uterine horn. The diagnosis of uterine anomaly was eventually
      made. The educational meaning of this rare case is that it is advisable to rule
      out uterine anomalies when signs of uterine rupture are suspected during
      pregnancy while contributory risk factors have not been identified. Besides, it
      is of vital importance to make a full assessment of both the mother and the fetus
      so to determine the appropriate time of termination.

PMID- 30288858
TI  - Preservation of the colo-anal reflex in colonic transection and post-operative
      Hirschsprung's disease: Potential extrinsic neural pathway.
AB  - BACKGROUND: The colo-anal reflex is a distinct reflex whereby the internal anal
      sphincter (IAS) relaxes in association with colonic high amplitude propagating
      contractions (HAPCs) in contrast to the recto-anal inhibitory reflex (RAIR),
      which is characterized by IAS relaxation upon rectal distension. The RAIR is
      mediated by the myenteric plexus and therefore absent in Hirschsprung disease. We
      retrospectively assessed the presence and the characteristics of the colo-anal
      reflex in children in whom large bowel continuity had been surgically disrupted
      to assess the role of the extrinsic nervous system in the reflex. METHODS: High
      resolution (HR) colonic manometry and HR-anorectal manometry were used to
      evaluate both colonic and anal motor activity in ten children with treatment
      unresponsive slow transit constipation (STC), who had previously undergone left
      sided colostomy formation with consequent disruption of the bowel continuity, and
      in two children with Hirschsprung's disease (HSCR), who had previously undergone
      distal colon resection followed by Duhamel pull-through. Eight children with STC,
      normal colonic motor activity, and preserved large bowel continuity served as a
      control group. The presence and characteristics of colo-anal reflex were
      analyzed. KEY RESULTS: In the study group, all patients showed the presence of
      both normal HAPCs and the presence of the colo-anal reflex. In two cases of HSCR,
      RAIR was absent; however, both patients demonstrated a colo-anal reflex.
      CONCLUSIONS: In children with disrupted continuity of the colon and/or abnormal
      anal reflex, the colo-anal reflex is still preserved suggesting that it is
      mediated by a different pathway from the RAIR, possibly an extrinsic neural
      pathway.

PMID- 30288860
TI  - Loganin prevents BV-2 microglia cells from Abeta1-42 -induced inflammation via
      regulating TLR4/TRAF6/NF-kappaB axis.
AB  - Neuroinflammation is closely related with the pathogenesis and progress of
      neurodegenerative diseases including Alzheimer's disease (AD). Loganin, an
      iridoid glycoside obtained from traditional Chinese medicine Cornus officinalis,
      has properties of inhibiting inflammation and improving memory. The present study
      was aimed to investigate effects of loganin on Abeta-induced inflammation and to
      explore the underlying mechanisms. BV-2 microglia cells were stimulated with 10
      uM Abeta1-42 for 24 h to induce inflammatory damage. According to results of CCK
      8 assay, the doses of loganin in present work were 10 and 30 uM. We found that
      treatment with loganin could inhibit Abeta1-42 -induced microglia activation.
      Furthermore, loganin treatment prevented the over-production of Tumor necrosis
      factor-alpha (TNF-alpha), Interleukin-6 (IL-6), Macrophage Chemotactic Protein
      1(MCP-1), Nitric oxide (NO), Prostaglandin E2 (PGE2) and the up-regulation of
      inducible nitric oxide synthase (iNOS) and Cyclooxygenase 2 (COX-2) in Abeta1-42 
      stimulated BV-2 cells. Results from Western blots demonstrated that loganin
      inhibited Abeta1-42 -induced elevation in Toll-like receptor 4 (TLR4), Myeloid
      Differentiation Factor 88 (MyD88) and TNF receptor-associated factor 6 (TRAF6).
      Loganin treatment also attenuated the increased phosphorylation level of IRAK4
      caused by Abeta1-42 . Additionally, loganin alleviated nuclear translocation of
      NF-kappaB p65 subunit in Abeta1-42 -stimulated BV-2 cells, and this phenomenon
      could be reversed by TLR4 agonist LPS. Further, the anti-inflammatory effects of
      loganin were attenuated when TLR4 signaling pathway was re-activated by LPS.
      Taken together, our data indicated that loganin could attenuate inflammatory
      response induced by Abeta in BV-2 microglia cells, partially through deactivating
      the TLR4/TRAF6/NF-kappaB axis.

PMID- 30288861
TI  - Inpatient disposition in overcrowded hospitals: is it safe and effective to use
      reverse triage and readmission screening tools for appropriate discharge? An
      observational prospective study of an Italian II level hospital.
AB  - BACKGROUND: Reverse triage (RT) identifies patients eligible for discharge and
      have been proposed to cope with daily surge. Nevertheless, early discharge could
      increase the rate of readmission. Our aim is to test the effectiveness and safety
      of RT alone and with readmission screening tools (Identification Senior At Risk
      [ISAR], HOSPITAL, and Groeningen Frailty Index [GFI] scores) to predict
      appropriate discharge. MATERIAL AND METHODS: We prospectively assessed every 4
      days (t0 ) inpatients of medical divisions (High Dependency Unit (HDU), Internal
      Medicine (IM), and Geriatrics (Ger)) of an Italian Hospital. RT score was
      calculated for each patient and an RT <=3 identified those eligible for safe
      discharge. ISAR, HOSPITAL, and GFI were then applied. We assessed reinstituting
      of interventions and transferring to an increased level of care unit at 4 days as
      an ethical proxy of consequential medical events following hypothetical
      discharge. Date of effective discharge, death, and readmission were measured at
      4, 7, 15, and 30 days after the first evaluation. RESULTS: Twenty-five (9.6%) out
      of 260 patients in our sample had an RT <=3. Twenty-four (96%) of them compared
      with 205 (87%) of the RT >3 group (P = NS) were discharged. Patients with RT <=3
      were discharged significantly earlier (3.5 vs 8 days after t0 [P = 0.0002]). In
      the RT <=3 group, all but one patient were alive and healthy at 7, 15, and 30
      days. The HOSPITAL score seemed to have the best concordance with RT (84%), in
      comparison with the ISAR (52%) and the GFI (48%) scores. RT showed a low
      sensitivity (22%) and high specificity (95%), which was even higher when using RT
      associated with readmission screening tools. CONCLUSIONS: Reverse triage proved
      to be a safe and conservative tool, with high specificity alone and with
      readmission screening tools. RT correctly identifies patients that will be
      discharged earlier.

PMID- 30288863
TI  - A case report demonstrating potential utility of topical imiquimod for cutaneous
      Rosai-Dorfman disease.

PMID- 30288862
TI  - Grape berry surface bacterial microbiome: impact from the varieties and clones in
      the same vineyard from central China.
AB  - AIMS: Bacterial microbiome on grape berry surface may play an important role in
      grape quality and health. This study aims to investigate the impact of grape
      varieties and clones on grape berry surface bacterial microbiome from the same
      vineyard. METHODS AND RESULTS: High-throughput sequencing strategy was used to
      investigate the bacterial diversity and abundance on the grape surfaces of 12
      clones belonging to six varieties grown in the same vineyard of Zhengzhou Fruit
      Research Institute in Henan Province. In total, 45 bacterial phyla and 933 genera
      were detected from all samples. Cyanobacteria, Proteobacteria and Firmicutes were
      the most abundant and prevalent phyla, while Bacteroidetes, Chloroflexi,
      Acidobacteria and Planctomycetes were grape clone specific phyla. The nonrank
      genus from phylum Cyanobacteria occupied 30-81% of grape clones from Italian
      Riesling (GRX), Cabernet Franc (PLZ), Pinot Blanc (BBN) and Riesling (LSL).
      Interestingly, Bacillus, Pseudomonas and Lactococcus were the only three
      prevalent genera found on all the clones. Furthermore, the predicted functional
      activities of grape surface bacterial communities varied according to the clones.
      CONCLUSIONS: The present study revealed that in addition to the grape varieties,
      the variations in grape clone background may also affect the bacterial microbiome
      on grape surfaces which may ultimately determine their functional activities.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This research provides an important
      information for grape planting and wine fermentation that not only the grape
      varieties need to be paid attention but also grape clones from the specific
      variety need to be concerned.

PMID- 30288864
TI  - Letter to 'Intermittent aortic balloon occlusion combined with cesarean section
      for the treatment of patients with placenta previa complicated by placenta
      accreta: A retrospective study': Some concerns.

PMID- 30288865
TI  - Phylogenetic identificationI of lactic acid bacteria isolates and their effects
      on the fermentation quality of sweet sorghum (sorghum bicolor) silage.
AB  - AIM: to isolate, screen and identify the lactic acid bacteria (LAB) from elephant
      silage during the process of the fermentation and their effects on the
      fermentation quality of sweet sorghum silage. METHODS AND RESULTS: The isolated
      strains were identified based on morphological, physiological and biochemical
      characteristics as well as 16S rRNA analysis. Seven LAB strains were isolated
      from elephant grass silage. Three strains (Pediococcus acidilactici (AZZ1),
      Lactobacillus plantarum subsp. Plantarum (AZZ4), Lactobacillus plantarum subsp.
      Argentoratensis (AZZ7) and one commercial bacteria Lactobacillus Plantarum,
      Ecosyl MTD/1(CB)) were chosen as additives at 6 log colony forming units (cfu)/g
      of fresh sweet sorghum grass in laboratory silos (680g). Silos for each treatment
      were opened after 5, 7, 14, 30 and 60 d, respectively.All isolates were
      characterized as gram-positive, catalase-negative and grow normally in 6.5%
      NaCl.The strains AZZ1, AZZ2, and AZZ5, were identified as Pediococcus genus while
      AZZ3, AZZ4, AZZ6, and AZZ7 were Lactobacillus genus.Compared to the control, all
      the isolatesimproved the silage quality of sweet sorghum silage, indicated by
      significantly (P<0.05) lower pH and ammonia nitrogen (NH3 -N) contents and
      undesirable microorganism counts, and higher lactic acid (LA) contents and ratios
      of lactic acid/acetic acid (LA/AA). During ensiling, AZZ4 performed better among
      of all inoculants, indicated by significantly (P<0.05) decreased on pH and
      ammonia-N contents and higher increased on lactic acid contents. CONCLUSION:
      strain AZZ4 is recommended as starter culture for sweet sorghum. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This is the first time to investigate the effects of lactic
      acid bacteria isolates from elephant grass silage and use them as additives,
      which is to find out how LAB inoculants improve the fermentation quality of sweet
      sorghum silage. This article is protected by copyright. All rights reserved.

PMID- 30288866
TI  - Exploration of the Impact of Brief Noninvasive Vagal Nerve Stimulation on EEG and
      Event-Related Potentials.
AB  - OBJECTIVES: The primary objective of this study was to explore the impact of
      noninvasive Vagal Nerve Stimulation (nVNS) on brain electrophysiology, as
      assessed through spontaneous resting-state EEG and stimulus-driven event-related
      potentials (ERPs). METHODS: A hand-held transcutaneous stimulator was placed on
      the neck over the main branch of the left vagus (active condition) or more
      laterally over neck muscles (sham condition), with two 120-sec long bursts of
      stimulation applied over a five-minute period. For each of eight neurotypical
      subjects, prior to stimulation, and then again beginning at 15, 120, and 240 min
      post-stimulation, ten minutes of background EEG data were collected, along with a
      series of ERPs-N100 auditory sensory-gating; the N1/P2 loudness dependent
      auditory evoked responses (LDAER); mismatch negativity; P300a; and P300b. Each
      subject participated in active and sham stimulation sessions. RESULTS: Brief nVNS
      had a significant (p < 0.05), and in some cases prolonged (>2 hours), impact on
      the spontaneous EEG (decreased theta and alpha, and increased beta and gamma),
      and on sensory gating, LDAER, and P300b evoked responses. Based on prior
      literature, these specific observations may reflect nVNS-induced modulation of
      particular neurotransmitter systems including those for GABA (gamma power and
      frequency); acetylcholine (sensory gating); serotonin (LDAER); and noradrenaline
      (P300b). CONCLUSIONS: Brief nVNS leads to changes in a sub-set of resting-state
      and event-related electrophysiologic indices of brain activity. These changes are
      believed to be mediated by vagal afferent projections to the nucleus of the
      solitary tract, which in turn regulates several neurotransmitter systems through
      known direct and indirect neuroanatomic pathways.

PMID- 30288868
TI  - Mexican-American adolescents' perceptions about causes of perinatal depression,
      self-help strategies, and how to obtain mental health information.
AB  - PROBLEM: Perinatal depression is a public health concern as it is associated with
      adverse pregnancy outcomes. Previous studies have recommended further examination
      of perinatal depression among Mexican-American adolescents. Thus, the purpose of
      this study was to understand pregnant and postpartum Mexican-American
      adolescents' knowledge and beliefs concerning perinatal depression. METHODS: This
      qualitative descriptive study examined perceptions about the causes of perinatal
      depression, self-help strategies, and how to obtain mental health information.
      Data were analyzed using deductive and inductive qualitative content analysis. A
      convenience sample, consisiting of 20 pregnant and postpartum adolescents, self
      identified as Mexican-Americans, between the ages of 15 and 19 years was
      interviewed. FINDINGS: The quality of relationships with their family and
      significant other and difficulties in transitioning to motherhood were described
      as potential causes for depression. Journaling, exercising, and spending time
      with friends and family were identified as self-help strategies. Healthcare
      providers, the internet, and mothers who have experienced depression were stated
      as helpful sources of mental health information. CONCLUSION: An assessment of
      their psychosocial environment is indicated to identify risk or protective
      factors for perinatal depression. Its consideration and inclusion in
      interventions may optimize mental health among perinatal adolescents.

PMID- 30288869
TI  - Estimated cost efficacy of U.S. Food and Drug Administration-approved treatments
      for acne.

PMID- 30288867
TI  - Recombinant human follicle stimulating hormone purification by a short peptide
      affinity chromatography.
AB  - Peptide KVPLITVSKAK was selected to design a synthetic ligand for affinity
      chromatography purification of recombinant human follicle stimulating hormone
      (rhFSH), based on the interaction of the hormone with the exoloop 3 of its
      receptor. The peptide was acetylated to improve its stability to degradation by
      exopeptidases. A cysteine was incorporated at the C-termini to facilitate its
      immobilization to the chromatographic activated SulfoLink agarose resin. A sample
      of crude rhFSH was loaded to the affinity column, using 20 mM sodium phosphate,
      0.5 mM methionine, and pH 5.6 and 7.2 as adsorption and elution buffers,
      respectively. The dynamic capacity of the matrix was 54.6 mg rhFSH/mL matrix and
      the purity 94%. The percentage of oxidized rhFSH was 3.4%, and that of the free
      subunits was 1.2%, both in the range established by the European Pharmacopeia, as
      also were the sialic acid content and the isoforms profile.

PMID- 30288870
TI  - Characterization of a peptide containing the major heparin binding domain of
      human hepatic lipase.
AB  - Human hepatic lipase (hHL) is a cell surface associated enzyme that hydrolyzes
      triacylglycerols and phospholipids within circulating lipoproteins. We
      hypothesized that an amino acid sequence mimicking the major heparin binding
      domain (HBD) of hHL will displace hHL from cell surfaces. To test this
      hypothesis, we generated a recombinant protein of thioredoxin linked with a
      cleavable, tagged sequence containing amino acids 442 to 476 of the mature hHL
      sequence, which contains the major HBD of hHL. The recombinant protein associated
      with heparin-sepharose, and its peak elution from heparin-sepharose occurred in
      the presence of 0.5 M NaCl. We cleaved and purified the tagged sequence
      containing the HBD from the recombinant protein and tested the ability of the
      peptide to displace full-length hHL from HEK-293 cells. The peptide indeed
      displaced hHL from cell surfaces, while no significant displacement was observed
      in the presence of a peptide with a scrambled sequence. Finally, we obtained
      structural information for the peptide containing the HBD. 1 H- and 15 N-NMR
      spectra of the peptide indicate the peptide is largely unstructured, although not
      completely random coil. The addition of heparin to the peptide induced some
      changes in chemical shift, suggesting changes in peptide structure and/or
      specific interactions with heparin. Molecular simulations confirm the largely
      unstructured nature of the isolated peptide, but they also indicate weak
      tendencies for both alpha- and beta-structure formation in different parts of the
      chain. Overall, these data provide a proof-of-principle for the use of mimetic
      peptides for the displacement of cell surface associated lipases.

PMID- 30288871
TI  - Paradox of meritocracy in surgical selection, and of variation in the
      attractiveness of individual specialties: to what extent are women still
      disadvantaged?
AB  - BACKGROUND: Evidence from outside surgery suggests that meritocracy-based
      processes around selection tend to reduce, rather than increase, diversity. In
      recent years, the surgical training boards have gone to considerable effort to
      achieve greater transparency and fairness in their selection processes, and to
      identify those attributes that are believed to best predict future success as a
      surgeon. This is consistent with the Royal Australasian College of Surgeons
      Diversity and Inclusion Plan, which places emphasis on gender equity and has
      goals that include increasing the attractiveness of surgery as a vocation for
      women, removing impediments to them applying to the surgical training programmes
      and removing any biases that might disadvantage them during the selection
      process. METHODS: This study uses the Female Opportunity Index and rate ratio
      metrics to measure the level of female disadvantage in surgical selection,
      whether it be by the perception of its attractiveness to women which influences
      their application rates, or by the likelihood of successful selection for those
      who have applied, compared with their male counterparts. RESULTS: There are
      marked differences between the nine surgical specialties and 13 specialty
      training boards in both the proportion of women who apply, and the proportion who
      are successful in gaining entry onto the Surgical Education and Training
      programmes. The Female Opportunity Index ranged from 0.21 to 0.87, which
      represents a wide variation between surgical specialties. CONCLUSION: These data
      raise the question as to whether unconscious bias is occurring in an apparently
      meritocracy-based selection process in some specialties. The data also suggest
      that some specialties are relatively unattractive to women, for which the reasons
      are likely to be complex.

PMID- 30288872
TI  - Secondary failure of TNF-alpha inhibitors in clinical practice.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a leading inflammatory cytokine that
      plays a pivotal role in the pathogenesis of psoriasis. In case of a severe course
      of psoriasis and moderate-to-severe disease in which traditional systemic
      treatments are ineffective or contraindicated, TNF-alpha inhibitors (iTNF-alpha)
      are used. This class of drugs includes monoclonal antibodies and a fusion protein
      (etanercept) and can induce a humoral or cell-mediated immune response, leading
      to formation of anti-drug antibodies (ADAs). The immunogenicity may affect iTNF
      alpha drug pharmacokinetics, which would lead to hampering the clinical response
      (secondary drug failure), so a need to increase the drug dose arises. Antibodies
      against monoclonal antibodies (adalimumab, infliximab) have been associated with
      diminished clinical response, while against etanercept are non-neutralizing and
      appear to have no significant effect on clinical response and treatment safety.
      Switching of biologic agents may be one strategy in ADA-associated secondary
      failure of iTNF-alpha. However researches are needed to identify risk factors for
      ADA development and investigate management strategies for optimized treatment
      response. The authors reviewed the literature on the effectiveness of iTNF-alpha
      and pointed out the prevention of secondary failure in clinical practice.

PMID- 30288873
TI  - Transabdominal selective feticide in dichorionic twins: Ten years' experience at
      a single center.
AB  - AIM: The present study investigates the procedure-related fetal loss rate and
      obstetrical outcomes of selective feticide in dichorionic twins. METHODS: We
      retrospectively analyzed the data of 44 cases of dichorionic twins. Two different
      indications for selective feticide were set: (i) the presence of genetic or
      congenital anomaly; and (ii) an obstetrical indication specified as a past
      maternal history of preterm delivery that caused fetal death or cerebral palsy of
      the child. Primarily, data on procedure-related fetal loss and obstetrical
      outcomes were retrieved. Additionally, data on obstetrical outcomes by reduction
      time and by indication of SF were obtained. RESULTS: Selective feticide was
      performed in 44 cases - specifically, in 23 cases with genetic or congenital
      anomaly and in 21 cases with obstetrical indications. The median gestational age
      at delivery was 38 + 4 weeks. One pregnancy loss (2.3%, 1/44) occurred within 4
      weeks after the procedure. The overall pregnancy loss rate throughout the
      pregnancy term was 2.3% (1/44). When selective feticide was performed at 15 weeks
      and beyond, the birth weight was significantly decreased compared with when
      selective feticide was performed earlier than 15 weeks. CONCLUSION:
      Transabdominal ultrasound-guided selective feticide in dichorionic twins is an
      effective and safe procedure. If a patient desires to maximize her chances of
      having a healthy child and decrease the risk of prematurity, the option of
      selective feticide should be considered in certain cases of twin pregnancies.
      Selective feticide may be a reasonable alternative to expectant management or
      termination of the whole twin pregnancy.

PMID- 30288874
TI  - New alcohol flushing in a patient with atopic dermatitis under therapy with
      dupilumab.

PMID- 30288875
TI  - Implication of SLIT3-ROBO1/ROBO2 in granulosa cell proliferation, differentiation
      and follicle selection in the prehierarchical follicles of hen ovary.
AB  - The SLIT/ROBO pathway has been implicated in prehierarchical follicular
      development of hen ovary by an intrafollicular autocrine and/or paracrine
      fashion. SLIT3, one of the key components of the SLIT/ROBO family, serves as a
      ligand that potentially interacts with the four receptors, ROBO1, ROBO2, ROBO3
      and ROBO4. But the exact roles and regulatory mechanism of SLIT3 in chicken
      ovarian follicle development remain largely unclear. The present study was
      conducted to investigate the potential roles and molecular regulation of SLIT3 in
      granulosa cell (GC) proliferation, differentiation and follicle selection within
      the prehierarchical follicles of hen ovary. We found that SLIT3 interacts
      physically with the four ROBO receptors, but the expression of the ROBO1 and
      ROBO2 genes are more susceptible to the regulation of SLIT3 ligand than that of
      the ROBO3 and ROBO4 genes. Moreover, the siRNA-mediated knockdown of SLIT3 in the
      follicular GCs leads to a significant increase in cell proliferation. Conversely,
      overexpression of SLIT3 results in a remarkable reduction in GC proliferation.
      Furthermore, the overexpressed SLIT3 has notably decreased the mRNA and protein
      expression levels of follicle-stimulating hormone (FSHR), growth and
      differentiation factor 9 (GDF9), steroidogenic acute regulatory protein (STAR)
      and cytochrome P450 11A1 (CYP11A1) in the GCs. These results indicated that SLIT3
      may play an inhibitory effect on GC proliferation, differentiation and follicle
      selection, and these suppressive actions of SLIT3 in the GC proliferation can be
      prohibited by the siRNA-mediated knockdown of ROBO1 and ROBO2 receptors. The
      current data provide a basis for further investigation of molecular mechanisms of
      SLIT3-ROBO1/2 pathway in controlling the prehierarchical follicle development of
      the hen ovary.

PMID- 30288876
TI  - Experimentally manipulating light spectra reveals the importance of dark
      corridors for commuting bats.
AB  - The rapid global spread of artificial light at night is causing unprecedented
      disruption to ecosystems. In otherwise dark environments, street lights restrict
      the use of major flight routes by some bats, including the threatened lesser
      horseshoe bat Rhinolophus hipposideros, and may disrupt foraging. Using radio
      tracking, we examined the response of individual female R. hipposideros to
      experimental street lights placed on hedgerows used as major flight routes.
      Hedgerows were illuminated on one side over four nights using lights with
      different emission spectra, while the opposite side of the hedge was not
      illuminated. Automated bat detectors were used to examine changes in overall bat
      activity by R. hipposideros and other bat species present. R. hipposideros
      activity reduced significantly under all light types, including red light,
      challenging a previously held assumption that red light is safe for bats. Despite
      this, R. hipposideros rapidly adapted to the presence of lights by switching
      their flight paths to the dark side of the hedgerow, enabling them to reach
      foraging sites without restriction. Red light had no effect on the activity of
      the other species present. Slow-flying Myotis spp. avoided orange, white and
      green light, while more agile Pipistrellus spp. were significantly more active at
      these light types compared to dark controls, most probably in response to
      accumulations of insect prey. No effect of any light type was found for Nyctalus
      or Eptesicus spp. Our findings demonstrate that caution must be used when
      promoting forms of lighting that are thought to be safe for wildlife before they
      are tested more widely. We argue that it is essential to preserve dark corridors
      to mitigate the impacts of artificial light at night on bat activity and
      movements.

PMID- 30288877
TI  - Rituximab therapy in pemphigus: A long-term follow-up.

PMID- 30288878
TI  - Supramolecular Electropolymerization.
AB  - Gaining control over supramolecular polymerization mechanisms is of high
      fundamental interest to understand self-assembly and self-organization processes
      at the nanoscale. It is also expected to significantly impact the design and
      improve the efficiency of advanced materials and devices. Up to now,
      supramolecular polymerization has been shown to take place from unimers in
      solution, mainly by variations of temperature or of concentration. Reported here
      is that supramolecular nucleation-growth of triarylamine monomers can be
      triggered by electrochemistry in various solvents. The involved mechanism offers
      new opportunities to precisely address in space and time the nucleation of
      supramolecular polymers at an electrode. To illustrate the potential of this
      methodology, supramolecular nanowires are grown an oriented over several tens of
      micrometers between different types of commercially available electrodes
      submitted to a single DC electric field, reaching a precision unprecedented in
      the literature.

PMID- 30288879
TI  - A DNA priming and protein boosting immunization scheme to augment immune
      responses against parvovirus in ducks.
AB  - AIMS: To evaluate the effect of a DNA priming and protein boosting immunization
      scheme in ducks. METHODS AND RESULTS: Pekin ducks were immunized with pTCY/VP2
      DNA vaccine; on day 14 (D14) after primary immunization, the ducks were boosted
      with either the same vaccine (DNA + DNA) or the rVP2 vaccine (DNA + rVP2). CpG
      oligodeoxynucleotides containing three copies of GACGTT motifs were used as the
      adjuvant in the vaccines. Compared with unimmunized controls, both immunization
      schemes significantly increased the titre of antigen-specific antibodies,
      lymphocyte proliferation index, percentage of CD4+ and CD8+ cells in peripheral
      blood mononuclear cells (PBMCs) and mRNA expression of interferon (IFN)-alpha,
      IFN-gamma, interleukin (IL)-6 and IL-12 in antigen-stimulated PBMCs. Furthermore,
      compared with the DNA + DNA homologous scheme, the DNA + rVP2 heterologous scheme
      significantly increased lymphocyte proliferation, percentage of CD4+ and CD8+
      cells in PBMCs and upregulation of mRNA expression of cytokines 2 weeks after the
      boost (D28). CONCLUSIONS: The DNA + rVP2 immunization scheme enhanced immune
      responses, mainly Th1 type, against parvovirus in ducks. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The DNA priming and protein boosting heterologous immunization
      strategy can be applied to develop vaccines against viral infections in ducks. It
      can potentially be used in breeding ducks because of long-term immunity may
      confer protection for ducklings.

PMID- 30288880
TI  - Ocular abnormalities in a herd of Old Kladruber Horses: A cross-sectional study.
AB  - OBJECTIVE: To screen a closed herd of the Old Kladruber Horses (OKH) for the
      prevalence of ocular disorders and report normal ocular variations. ANIMALS
      STUDIED: Two hundred and sixty-one horses, 122 Old Kladruber Gray Horses, and 139
      Old Kladruber Black Horses owned by the National Stud Farm Kladruby nad Labem,
      Czech Republic, were included in the study with signalment and pedigree
      information recorded. PROCEDURES: Bilateral ocular examination of manually
      restrained horses was performed in a darkened environment by a single examiner
      (RA), using a portable slit-lamp biomicroscope, direct ophthalmoscope, and
      monocular indirect ophthalmoscopy using a Finnoff transilluminator and 20 D
      condensing lens. Fluorescein testing was performed when indicated. RESULTS: The
      animal ages ranged from 3 months to 27 years (mean 7.82 years, median 6 years).
      The gender ratio (males:females) was 109:152. Ophthalmological abnormalities were
      found in 133 (50.96%) horses; with right and left eyes affected equally. The most
      common abnormalities were cataract formation (35 horses), iris hyperpigmentation
      (29 horses), alterations in corpora nigra size (26 horses), nonsenile vitreal
      degeneration (24 horses), linear keratopathy (11 horses), corneal stromal haze
      (nine horses) and corneal subepithelial punctate opacities (nine horses). The
      most frequent variations of normal ocular anatomy were posterior lenticular
      suture lines (222 horses), tapetal hypoplasia (95 horses) resulting in a multi
      colored tapetal fundus (31 horses), nuclear sclerosis (48 horses), and senile
      vitreal degeneration (30 horses). CONCLUSIONS: Ocular disorders were relatively
      common in OKH, but typically not vision threatening and not interfering with the
      quality of life.

PMID- 30288881
TI  - Intralesional 2% zinc sulfate solution for plane warts: A case report.
AB  - Warts are benign epithelial proliferations of the skin and mucous membranes
      caused by human papilloma viruses (HPVs). Plane warts are mainly caused by HPV-3
      and HPV-10. There is no absolute effective single treatment, and multiple
      treatment modalities may be combined. One must take into consideration the
      probability of spontaneous regression, and so the therapeutic approach should not
      be too aggressive. We report a case of 11 years immunocompetent child presenting
      with recalcitrant multiple plane warts who was successfully treated with
      intralesional 2% zinc sulfate solution injection in one lesion after a failure of
      many other treatment modalities. Our case may represent a starting point for
      further studies to evaluate the best dose used for management and to avoid any
      side effects. Intralesional zinc sulfate injection could be a promising treatment
      option for plane warts.

PMID- 30288882
TI  - Single embryo transfer with frozen transfer of all remaining embryos without
      further embryonic testing should be the standard of care in IVF.

PMID- 30288883
TI  - The COLLECT database: momentum to improve our research standards, methods, and
      culture.

PMID- 30288884
TI  - Evaluation of axitinib to downstage cT2a renal tumours and allow partial
      nephrectomy: a phase II study.
AB  - OBJECTIVE: To evaluate the ability of neoadjuvant axitinib to reduce the size of
      T2 renal cell carcinoma (RCC) for shifting from a radical nephrectomy (RN) to a
      partial nephrectomy (PN) indication, offering preservation of renal function.
      PATIENTS AND METHODS: Patients with cT2aN0NxM0 clear-cell RCC, considered not
      suitable for PN, were enrolled in a prospective, multicentre, phase II trial
      (AXIPAN). Axitinib 5 mg, and up to 7-10 mg, was administered twice daily, for 2-6
      months before surgery, depending on the radiological response. The primary
      outcome was the number of patients receiving PN for a tumour <7 cm in size after
      neoadjuvant axitinib. RESULTS: Eighteen patients were enrolled. The median
      (range) tumour size and RENAL nephrometry score were 76.5  (70-98) mm and 11 (7
      11), respectively. After axitinib neoadjuvant treatment, 16 tumours decreased in
      diameter, with a median size reduction of 17% (64.0 vs 76.5 mm; P < 0.001). The
      primary outcome was considered achieved in 12 patients who underwent PN for
      tumours <7 cm. Sixteen patients underwent PN. Axitinib was tolerated in the
      present study, as has been previously shown in the metastatic setting. Five
      patients had grade 3 adverse events. Five patients experienced Clavien III-V post
      surgery complications. At 2-year follow-up, six patients had metastatic
      progression, and two had a recurrence. CONCLUSION: Neoadjuvant axitinib in cT2
      ccRCC is feasible and, even with a modest decrease in size, allowed a tumour
      shrinkage <7 cm in 12 cases; however, PN procedures remained complex, requiring
      surgical expertise with possible morbidity.

PMID- 30288886
TI  - Rapid, Quantitative, and Ultrasensitive Point-of-Care Testing: A Portable SERS
      Reader for Lateral Flow Assays in Clinical Chemistry.
AB  - The design of a portable Raman/SERS-LFA reader with line illumination using a
      custom-made fiber optic probe for rapid, quantitative, and ultrasensitive point
      of-care testing (POCT) is presented. The pregnancy hormone human chorionic
      gonadotropin (hCG) is detectable in clinical samples within only 2-5 s down to
      approximately 1.6 mIU mL-1 . This acquisition time is several orders of magnitude
      shorter than those of existing approaches requiring expensive Raman
      instrumentation, and the method is 15-times more sensitive than a commercially
      available lateral flow assay (LFA) as the gold standard. The SERS-LFA technology
      paves the way for affordable, quantitative, and ultrasensitive POCT with
      multiplexing potential in real-world applications, ranging from clinical
      chemistry to food and environmental analysis as well as drug and biowarfare agent
      testing.

PMID- 30288885
TI  - Relationship between the Functional Independence Measure and Mann Assessment of
      Swallowing Ability in hospitalized patients with pneumonia.
AB  - AIM: Pneumonia ranks high among the causes of death worldwide. However, the
      predictive values of activities of daily living, the nutrition index and the
      aspiration index measured objectively remain unclear. The present study aimed to
      examine the associations of activity, nutrition and dysphagia with pneumonia.
      METHODS: We assessed 992 hospitalized patients. Logistic regression analysis was
      used to examine the predictors of pneumonia. Receiver operating characteristic
      curve analysis was used to determine the cut-off values of variables. Kaplan
      Meier and Cox hazards regression analyses were used to examine the incidence of
      pneumonia and the factors associated with pneumonia. RESULTS: We finally enrolled
      393 inpatients. Of the 393 patients, 102 (26.0%) had pneumonia. On logistic
      regression analysis, age, Functional Independence Measure (FIM)-motor score and
      Mann Assessment of Swallowing Ability (MASA) score were independent predictors of
      pneumonia. The FIM-motor and MASA cut-off values were 19.5 (area under the curve
      0.83, P < 0.01) and 170.5 (area under the curve 0.82, P < 0.01), respectively.
      Kaplan-Meier analysis showed that the no pneumonia rate was significantly lower
      among patients with FIM-motor scores <20 than among those with FIM-motor scores
      >=20 (log-rank test, P < 0.01), and was significantly lower among patients with
      MASA scores <171 than among those with MASA scores >=171 (log-rank test, P <
      0.01). Cox regression analysis showed that FIM-motor (hazard ratio 0.97, P =
      0.009) and MASA scores (hazard ratio 0.99, P < 0.01) were significantly
      associated with pneumonia. CONCLUSIONS: In addition to the infectious risk, the
      FIM-motor and MASA scales are useful tools to predict the development of
      pneumonia in older adults. Geriatr Gerontol Int 2018; **: **-**.

PMID- 30288887
TI  - A Tailored DNA Nanoplatform for Synergistic RNAi-/Chemotherapy of Multidrug
      Resistant Tumors.
AB  - Multidrug resistance (MDR) is a major obstacle in the clinical treatment of
      cancer. Herein, a facile strategy is reported to construct a versatile DNA
      nanostructure as a co-delivery vector of RNA interference (RNAi) and chemodrugs
      to combat multidrug-resistant tumor (MCF-7R) in vitro and in vivo. In the
      tailored nanocarrier, two linear small hairpin RNA (shRNA) transcription
      templates targeting MDR-associated genes (gene of P-glycoprotein, a typical drug
      efflux pump; and gene of survivin, a representative anti-apoptotic protein) are
      precisely organized in the chemodrug (doxorubicin, DOX) pre-loaded DNA origami.
      With the incorporation of active targeting and controlled-release elements, these
      multifunctional DNA nanocarriers can successfully enter the target MCF-7R cells
      and synergistically inhibit tumor growth without apparent systemic toxicity. This
      tailored DNA nanoplatform, which combines RNAi therapy and chemotherapy, provides
      a new strategy for the treatment of multidrug-resistant tumors.

PMID- 30288888
TI  - Genetic determinants of activity and antigen levels of contact system factors.
AB  - Essentials Genetic variation may provide valuable insight into the role of the
      contact system in thrombosis. Explored associations of genetic variants with
      activity, antigen, and disease in RATIO study. Two novel loci were identified:
      KLKB1 rs4253243 for prekallikrein; KNG1 rs5029980 for HMWK levels. Contact system
      variants and haplotypes were not associated with myocardial infarction or stroke.
      SUMMARY: Background The complex, interdependent contact activation system has
      been implicated in thrombotic disease, although few genetic determinants of
      levels of proteins from this system are known. Objectives Our primary aim was to
      study the influence of common F11, F12, KLKB1, and KNG1 variants on factor (F) XI
      activity and FXI, FXII, prekallikrein (PK) and high-molecular-weight kininogen
      (HMWK) antigen levels, as well as the risk of myocardial infarction and ischemic
      stroke. Patients/methods We analyzed samples from all 630 healthy participants,
      182 ischemic stroke patients and 216 myocardial infarction patients in the RATIO
      case-control study of women aged < 50 years. Forty-three tagging single
      nucleotide variants (SNVs) were genotyped to represent common genetic variation
      in the contact system genes. Antigen and activity levels were measured with
      sandwich-ELISA-based and one-stage clotting assays. We performed single variant,
      age-adjusted, linear regression analyses per trait and disease phenotype,
      assuming additive inheritance and determined conditionally independent
      associations. Haplotypes based on the lead SNV and all conditionally independent
      SNVs were tested for association with traits and disease. Results We identified
      two novel associations of KLKB1 SNV rs4253243 with PK antigen (betaconditional = 
      12.38; 95% CI, -20.07 to -4.69) and KNG1 SNV rs5029980 with HMWK antigen
      (betaconditional = 5.86; 95% CI, 2.40-9.32) and replicated previously reported
      associations in a single study. Further analyses probed whether the observed
      associations were indicative of linkage, pleiotropic effects or mediation. No
      individual SNVs or haplotypes were associated with the disease outcomes.
      Conclusion This study adds to current knowledge of how genetic variation
      influences contact system protein levels and clarifies interdependencies.

PMID- 30288889
TI  - Molecular stressors underlying exercise training-induced improvements in K+
      regulation during exercise and Na+ ,K+ -ATPase adaptation in human skeletal
      muscle.
AB  - Despite substantial progress made towards a better understanding of the
      importance of skeletal muscle K+ regulation for human physical function and its
      association with several disease states (eg type-II diabetes and hypertension),
      the molecular basis underpinning adaptations in K+ regulation to various stimuli,
      including exercise training, remains inadequately explored in humans. In this
      review, the molecular mechanisms essential for enhancing skeletal muscle K+
      regulation and its key determinants, including Na+ ,K+ -ATPase function and
      expression, by exercise training are examined. Special attention is paid to the
      following molecular stressors and signaling proteins: oxygenation, redox balance,
      hypoxia, reactive oxygen species, antioxidant function, Na+ ,K+ , and Ca2+
      concentrations, anaerobic ATP turnover, AMPK, lactate, and mRNA expression. On
      this basis, an update on the effects of different types of exercise training on
      K+ regulation in humans is provided, focusing on recent discoveries about the
      muscle fibre-type-dependent regulation of Na+ ,K+ -ATPase-isoform expression.
      Furthermore, with special emphasis on blood-flow-restricted exercise as an
      exemplary model to modulate the key molecular mechanisms identified, it is
      discussed how training interventions may be designed to maximize improvements in
      K+ regulation in humans. The novel insights gained from this review may help us
      to better understand how exercise training and other strategies, such as
      pharmacological interventions, may be best designed to enhance K+ regulation and
      thus the physical function in humans.

PMID- 30288890
TI  - When Does the Odds Ratio Not Equal the Relative Risk, and Why Should You Care?

PMID- 30288892
TI  - Octreotide as a bridge to definitive surgery in a patient with cirrhosis and a
      large spontaneous abdominal wall haematoma.

PMID- 30288891
TI  - Treatment of patients with primary retroperitoneal sarcoma: predictors of outcome
      from an Australian specialist sarcoma centre.
AB  - BACKGROUND: Several unanswered questions surround the management of
      retroperitoneal sarcoma (RPS). Guidelines recommend treatment by a
      multidisciplinary team at a specialized referral centre. The objective of this
      study was to describe the management of RPS at an Australian specialist sarcoma
      centre, comparing outcomes to international standards and analysing for
      predictors of local failure. METHODS: A retrospective review of a prospectively
      maintained database was performed on patients with RPS treated between 2008 and
      2016. A 5-year outcome analyses focussed on patients undergoing curative-intent
      surgery for primary, non-metastatic RPS. RESULTS: Eighty-eight patients underwent
      surgery for primary RPS. Five-year overall survival was 66%, 5-year freedom from
      local recurrence was 65% and 5-year freedom from distant metastasis was 71%.
      Overall survival was associated with tumour grade (hazard ratio (HR) 6.1, P <
      0.001) and histologic organ invasion (HR 5.7, P < 0.001). Variables associated
      with improved freedom from local recurrence were macroscopically complete
      resection (HR 0.14, P < 0.001) and neoadjuvant radiotherapy (HR 0.33, P = 0.014).
      Treatment at a specialist sarcoma centre was associated with a higher rate of
      preoperative biopsy and neoadjuvant radiotherapy (both with P < 0.001). There was
      a trend towards improved local control for patients undergoing surgery at a
      specialist centre (P = 0.055). CONCLUSION: This is the largest Australian series
      of RPS and outcomes are comparable to major international sarcoma centres.
      Patients treated at a specialist centre had higher rates of preoperative
      diagnosis and tailored therapy which was associated with improved outcomes.
      Patients with suspected RPS should be referred to a specialist centre for optimal
      preoperative evaluation and multidisciplinary management.

PMID- 30288893
TI  - Update on diagnosis and anticoagulant therapy for venous thromboembolism.
AB  - Venous thromboembolism (VTE) continues to be a common medical problem requiring
      the need for rapid treatment with anticoagulant therapy. Until the recent
      availability of the direct oral anticoagulants for treatment of VTE, the option
      for oral anticoagulation was limited to warfarin therapy. The addition of these
      new medications has been welcomed, but has led to added complexities in deciding
      the most appropriate agent for each patient based on individual risk factors.
      Furthermore, there are several circumstances where optimal duration of therapy is
      not well established. This article will focus on the diagnosis of VTE, the choice
      of anticoagulant and treatment duration.

PMID- 30288894
TI  - No live vaccines for people being treated with leflunomide.

PMID- 30288896
TI  - Immune thrombocytopenia in the setting of ovarian dermoid cysts: implications for
      diagnosis and management.

PMID- 30288895
TI  - Supporting the on-call primary care physician with community paramedicine.
AB  - Prior to being referred to the emergency department (ED), patients such as the
      frail elderly often call their primary care physician. However, the on-call
      primary care physician or covering provider does not always have the tools to
      make an accurate and safe assessment over the phone or to treat patients
      remotely. This often results in preventable transport to an ED, avoidable
      admissions and iatrogenic events. An opportunity exists to reduce unnecessary ED
      referrals by enhancing the capabilities of the on-call primary care physician. In
      this communication, we describe the development of a community paramedicine
      programme that supports on-call primary care providers managing a high-risk
      patient population with the goal of reducing avoidable ED referrals.

PMID- 30288897
TI  - Fatal acute aortic dissection after back blows and chest thrusts delivered for
      choking episode.

PMID- 30288898
TI  - Regulation of e-cigarettes.

PMID- 30288899
TI  - Absence of renal phenotype in hereditary haemorrhagic telangiectasia.
AB  - Hereditary haemorrhagic telangiectasia is characterised by abnormal blood vessel
      formation, producing telangiectasia and arteriovenous malformations in multiple
      organs. Information regarding possible renal involvement in hereditary
      haemorrhagic telangiectasia is limited. This study assessed renal structure and
      function in 11 patients with genetically confirmed diagnosis and known
      arteriovenous malformations in lung, liver, gastrointestinal tract or brain. All
      had significant current or past epistaxis. Despite the vascularity of the
      kidneys, we found no evidence of renal involvement. This observation warrants
      further consideration.

PMID- 30288900
TI  - Decompressive hemicraniectomy after malignant middle cerebral artery infarction:
      does hospital of origin matter?
AB  - Decompressive hemicraniectomy (DHC) has been shown to reduce mortality in
      malignant middle cerebral artery (MCA) infarction. Our primary objective was to
      compare 1-year mortality between patients receiving DHC for malignant MCA
      infarction at our institution based on hospital of origin. We retrospectively
      reviewed the medical records of all patients treated for malignant MCA infarction
      with DHC at our institution over a 3-year period. One-year mortality rates and
      time to surgery were comparable regardless of whether the patient first attended
      the tertiary referral centre or a peripheral centre.

PMID- 30288902
TI  - How much end-of-life care is of low value.

PMID- 30288901
TI  - Low rates of eligibility for lung cancer screening in patients undergoing
      computed tomography coronary angiography.
AB  - Incidental findings, including pulmonary nodules, on computed tomography coronary
      angiography (CTCA) are common. Previous authors have suggested CTCA could allow
      opportunistic screening for lung cancer, though the lung cancer risk profile of
      this patient group has not previously been established. Smoking histories of 229
      patients undergoing CTCA at two tertiary hospitals were reviewed and only 25%
      were current or former smokers aged 55-80 years old. Less than half of this group
      were eligible for screening based on the PLCOm2012 risk model. We conclude that
      routine screening in the form of full thoracic field imaging, of individuals
      undergoing CTCA is not appropriate as it would likely result in net harm.

PMID- 30288903
TI  - Changing landscape of hereditary breast and ovarian cancer germline genetic
      testing in Australia.
AB  - Federal funding for germline genetic testing in hereditary breast and ovarian
      cancer (HBOC) was recently introduced. Germline testing for HBOC under Medicare
      Benefits Schedule items 73296/73297 can be requested by any specialist, whereas
      the previous state- and territory-funded testing was limited to those operating
      within a familial cancer service. The impact of this decentralisation of HBOC
      testing on health and economic outcomes is uncertain, primarily as it has
      potential to significantly disrupt the clinical framework that generated the
      evidence used to justify clinical implementation of the Medicare Benefits
      Schedules.

PMID- 30288904
TI  - Never too old for an inherited condition.
AB  - Primary ciliary dyskinesia is an uncommon, inherited condition causing
      progressive suppurative airway lung disease with subsequent bronchiectasis,
      chronic rhinitis-sinusitis, deafness and reduced fertility. Diagnosis is often
      delayed by lack of awareness of the condition in the medical community and
      limited access to the few centres in Australia able to do full diagnostic
      testing. This report details the late diagnosis of primary ciliary dyskinesia in
      two adults who have had long-standing interactions with medical services but in
      whom the diagnosis was never considered or even dismissed. Greater awareness of
      the condition will reduce time to diagnosis, prevent administration of
      ineffective therapy and allow earlier institution of targeted therapy.

PMID- 30288905
TI  - Author reply.

PMID- 30288906
TI  - Staff influenza vaccination rate in three major blood and marrow transplant units
      in New South Wales: room for improvement.

PMID- 30288908
TI  - Tear glucose, creatinine, and urea nitrogen concentrations in cats with normal or
      increased plasma concentrations.
AB  - OBJECTIVE: The aim of the study was to determine the lacrimal fluid (LF) contents
      of glucose, urea nitrogen, and creatinine in cats. ANIMAL STUDIED: A total of 96
      cats were included in the study. PROCEDURE: Venous blood and LF samples were
      collected. For LF sampling, three small polyurethane sponges were placed in the
      ventral fornix of both eyes. Both LF and plasma concentrations of glucose, urea
      nitrogen, and creatinine were quantitatively analyzed and compared. RESULT:
      Glucose (n = 40) and urea nitrogen concentrations (n = 42) measured in LF from
      both eyes highly correlated. While there was a very strong correlation (rho =
      0.97) between urea nitrogen concentrations in blood plasma and the corresponding
      tear levels (with the median LF urea nitrogen being 109% of that measured in
      plasma), the LF glucose concentrations were significantly lower than the
      corresponding plasma concentrations (with only 13% of the blood glucose
      concentration detected in the LF). The creatinine concentrations in tears were
      much lower than those in plasma, and LF creatinine was detectable in only 12/48
      cats (25%). Hence, a comparison of the LF creatinine concentrations between both
      eyes or with the corresponding plasma creatinine concentration was not possible.
      CONCLUSION: Measurement of LF urea nitrogen concentrations in cats appears to be
      reliable and might have potential clinical utility. Measurement of LF glucose
      concentrations is less reliable but may still be useful in some cats. Creatinine
      is not reliably detected in the LF in cats. Further studies determining clinical
      utility of LF metabolites in cats and other companion animals are warranted.

PMID- 30288907
TI  - Discovery of an MLLT1/3 YEATS Domain Chemical Probe.
AB  - YEATS domain (YD) containing proteins are an emerging class of epigenetic targets
      in drug discovery. Dysregulation of these modified lysine-binding proteins has
      been linked to the onset and progression of cancers. We herein report the
      discovery and characterisation of the first small-molecule chemical probe, SGC
      iMLLT, for the YD of MLLT1 (ENL/YEATS1) and MLLT3 (AF9/YEATS3). SGC-iMLLT is a
      potent and selective inhibitor of MLLT1/3-histone interactions. Excellent
      selectivity over other human YD proteins (YEATS2/4) and bromodomains was
      observed. Furthermore, our probe displays cellular target engagement of MLLT1 and
      MLLT3. The first small-molecule X-ray co-crystal structures with the MLLT1 YD are
      also reported. This first-in-class probe molecule can be used to understand
      MLLT1/3-associated biology and the therapeutic potential of small-molecule YD
      inhibitors.

PMID- 30288909
TI  - Improving the accuracy of the initial rise method and extending its applicability
      to evaluate the order of kinetics of TL glow peaks.
AB  - The classical initial rise method is limited to evaluate the activation energy
      for signal levels that do not exceed 10-15% of the maximum intensity. When it
      becomes necessary to include higher signal levels the associated error in the
      activation energy increases. In the present work we introduced a new correction
      factor for the activation energy obtained by the initial rise method in terms of
      the percentage of maximum intensity and the geometrical factor of the glow peak.
      The new expression reflects the dependence of the correction factor on the order
      of kinetics through the geometrical factor, especially when high signal levels
      are involved in the analysis. With this correction, the initial rise method can
      be applied to signal levels up to 70% of the maximum intensity with errors lower
      than those encountered in applying the classical method at low intensity levels
      (~10% of the maximum intensity). In addition, the order of kinetics was evaluated
      based on the difference between the corrected value of E and the one obtained by
      the initial rise method. The present procedure was applied to the glow curve of
      Li2 B4 O7 :Mn single crystal. The obtained parameters show very good agreement
      with curve fitting, peak shape methods and the published data on this material
      which supports the validity and reliability of the present approach.

PMID- 30288910
TI  - Sexual dimorphism in immunity across animals: a meta-analysis.
AB  - In animals, sex differences in immunity are proposed to shape variation in
      infection prevalence and intensity among individuals in a population, with
      females typically expected to exhibit superior immunity due to life-history trade
      offs. We performed a systematic meta-analysis to investigate the magnitude and
      direction of sex differences in immunity and to identify factors that shape sex
      biased immunocompetence. In addition to considering taxonomic and methodological
      effects as moderators, we assessed age-related effects, which are predicted to
      occur if sex differences in immunity are due to sex-specific resource allocation
      trade-offs with reproduction. In a meta-analysis of 584 effects from 124 studies,
      we found that females exhibit a significantly stronger immune response than do
      males, but the effect size is relatively small, and became non-significant after
      controlling for phylogeny. Female-biased immunity was more pronounced in adult
      than immature animals. More recently published studies did not report
      significantly smaller effect sizes. Among taxonomic and methodological subsets of
      the data, some of the largest effect sizes were in insects, further supporting
      previous suggestions that testosterone is not the only potential driver of sex
      differences in immunity. Our findings challenge the notion of pervasive biases
      towards female-biased immunity and the role of testosterone in driving these
      differences.

PMID- 30288911
TI  - A "seasonal bromoderma" in a farmer.
AB  - Bromoderma is a rare skin disease caused by the ingestion, inhalation, or contact
      with products containing bromides. We report a case of bromoderma in a 36-year
      old farmer, characterized by remission during the spring and exacerbation during
      the winter. The recognition of the use of products containing bromides during the
      winter helped us to understand the cause of the clinical condition.

PMID- 30288912
TI  - Cell Wall Proteome Investigation of Bread Wheat (Triticum Aestivum) Developing
      Grain in Endosperm and Outer Layers.
AB  - The remodeling of cell wall polysaccharides is controlled by cell wall proteins
      (CWPs) during the development of wheat grain. This work describes for the first
      time the cell wall proteomes of the endosperm and outer layers of the wheat
      developing grain, which have distinct physiological functions and technological
      uses. Altogether 636 nonredundant predicted CWPs are identified with 337 proteins
      in the endosperm and 594 proteins in the outer layers, among which 295 proteins
      are present in both tissues, suggesting both common and tissue specific
      remodeling activities. These proteins are distributed into eight functional
      classes. Approximatively a quarter of them were predicted to act on cell wall
      polysaccharides, with many glycosylhydrolases and also expansin, lyases, and
      carbohydrate esterases. Therefore, these results provide crucial data to go
      further in the understanding of relationship between tissue-specific
      morphogenesis and cell wall remodeling in cereals. Data are available via
      ProteomeXchange with identifier PXD010367.

PMID- 30288914
TI  - Continuing Professional Development.

PMID- 30288913
TI  - Does the robot have a role in radical cystectomy?

PMID- 30288915
TI  - More than meets the eye: an association between diet soft drink consumption and
      proliferative diabetic retinopathy.

PMID- 30288916
TI  - When does visual acuity stabilize after macular hole surgery? Five-year follow-up
      of surgery for idiopathic macular hole.

PMID- 30288917
TI  - Merging images with different central frequencies reduces banding artifacts in
      balanced steady-state free precession magnetic resonance cisternography.
AB  - PURPOSE: The aim of this study was to evaluate the utility of merged balanced
      steady-state free precession (bSSFP) magnetic resonance cisternography images.
      MATERIALS AND METHODS: Twenty ears of 10 healthy volunteers (six men, four women;
      mean age +/- standard deviation, 26.7 +/- 1.6 yr) and 10 patients (two men, eight
      women; mean age, 46.3 +/- 10.9 yr) with neoplasm around the sella turcica were
      included. Two different devices (A and B) were used to confirm the versatility of
      our method for MR devices with different local magnetic field homogeneity. Images
      with different central frequencies (+/-10, +/-20, +/-30, +/-40, and +/-50 Hz)
      were merged with the maximum magnitude of corresponding pixels from the images
      acquired using both devices. Two neuroradiologists visually graded the image
      quality of 11 sites in the inner ear and three sites around the sella turcica
      (scale: 0-2) and compared the quality with that of the corresponding basic image
      (0 Hz). RESULTS: The image quality was better in merged images of the vestibule,
      superior semicircular canal (SCC), posterior SCC, and horizontal SCC (P = 0.005
      to 0.020 mainly at +/-40 and +/-50 Hz on devices A and B), as well as in merged
      images of the sella turcica and right cavernous sinus (+/-50 Hz, P = 0.003 and
      0.020 on device B, respectively), than it was in the corresponding basic images.
      CONCLUSIONS: The maximum magnitude merging of images with different central
      frequencies makes it possible to reduce banding artifacts on bSSFP images without
      the need for special pulse sequences and image processing programs.

PMID- 30288918
TI  - Extended follow-up for prostate cancer incidence and mortality among participants
      in the Prostate, Lung, Colorectal and Ovarian randomized cancer screening trial.
AB  - OBJECTIVE: To examine prostate cancer (PCa) incidence and mortality by arm in the
      randomized Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial.
      PATIENTS AND METHODS: Patients aged 55-74 years at 10 screening centres were
      randomized between 1993 and 2001 to an intervention or usual care arm. Patients
      in the intervention arm received six annual prostate-specific antigen (PSA) tests
      and four annual digital rectal examinations. The patients were followed for PCa
      incidence and for mortality via active follow-up processes and by linkage to
      state cancer registries and the National Death Index. For cancers identified
      through active follow-up, trial abstractors recorded the mode of diagnosis
      (screen-detected, symptomatic, other). RESULTS: A total of 38 340 patients were
      randomized to the intervention arm and 38 343 to a usual care arm. The median
      follow-up for mortality was 16.9 (intervention) and 16.7 years (usual care).
      There were 333 (intervention) and 352 (usual care) PCa cancer deaths, giving
      rates (per 10 000 person-years) of 5.5 and 5.9, respectively, and a rate ratio
      (RR) of 0.93 (95% confidence interval [CI] 0.81-1.08; P = 0.38). The RR for
      overall PCa incidence was 1.05 (95% CI 1.01-1.09). The RRs by Gleason category
      were 1.17 (95% CI 1.11-1.23) for Gleason 2-6, 1.00 (95% CI 0.93-1.07) for Gleason
      7 and 0.89 (95% CI 0.80-0.99) for Gleason 8-10 disease. By mode of detection,
      during the trial's screening phase, 13% of intervention arm vs 27% of usual care
      arm cases were symptomatic; post-screening, these percentages were 18% in each
      arm. CONCLUSION: After almost 17 years of median follow-up, there was no
      significant reduction in PCa mortality in the intervention compared with the
      usual care arm. There was a significant increase in Gleason 2-6 disease and a
      significant reduction in Gleason 8-10 disease in the intervention compared with
      the usual care arm.

PMID- 30288919
TI  - Canonical Wnt/beta-catenin and Notch signaling regulate animal/vegetal axial
      patterning in the cephalochordate amphioxus.
AB  - In bilaterians, animal/vegetal axial (A/V) patterning is a fundamental early
      developmental event for establishment of animal/vegetal polarity and following
      specification of the germ layers (ectoderm, mesoderm, endoderm), of which the
      evolutionary origin is enigmatic. Understanding A/V axial patterning in a basal
      animal from each phylum would help to reconstruct the ancestral state of germ
      layer specification in bilaterians and thus, the evolution of mesoderm, the third
      intermediate cell layer. Herein, data show that the canonical Wnt/beta-catenin
      (cWnt) and Notch signaling pathways control mesoderm specification from the early
      endomesoderm in the basal chordate amphioxus. Amphioxus belongs to the
      deuterostome, one of the main superphyla in Bilateria. In the present study,
      genes (tcf, dsh, axin, gsk3beta) encoding cWnt components were expressed in the
      endomesoderm during the gastrula stages. Excess cWnt signaling by BIO, a GSK3
      inhibitor, expanded the expression domains of outer endomesodermal genes that
      include future mesodermal ones and suppressed inner endomesodermal and ectodermal
      genes. Interfering Notch signaling by DAPT, a gamma-secretase inhibitor, resulted
      in decreased expression of ectodermal and endomesodermal markers. These results
      suggest that cWnt and Notch have important roles in mesoderm specification in
      amphioxus embryos. The evolution of the mesoderm is also discussed.

PMID- 30288920
TI  - Gender-Specific Body Areas Satisfaction and Body Weight Status in Adolescents:
      Mediating Effects of Physical Activity, Fruit and Vegetable Intake, and Energy
      Dense Food Intake.
AB  - BACKGROUND: Body satisfaction is one of the key modifiable cognitive determinants
      of eating behaviours, physical activity, and body mass index (BMI). As the
      sociocultural models suggest, low body satisfaction may explain unhealthy eating
      and exercise behaviours. Importantly, body satisfaction levels and body areas
      that individuals focus on vary across genders. This study aims at investigating
      links between the global index of body areas satisfaction (BAS), gender-specific
      BAS, fruit and vegetable (F&V) intake, energy-dense foods intake, moderate-to
      vigorous physical activity (MVPA), and BMI. METHODS: In all, 1,254 adolescents
      completed questionnaires and had their weight and height objectively measured
      with 2- and 13-month follow-ups. Indirect effects of three indices of BAS were
      tested in three models (male-specific BAS amongst boys; female-specific BAS
      amongst girls; the global BAS index in the total sample). RESULTS: Higher levels
      of all three BAS indices indirectly predicted lower BMI, with higher MVPA
      mediating this effect. In addition, higher energy-dense foods intake mediated
      higher global BAS-higher BMI relationship in the total sample. Thus, the global
      index of BAS acts as double-edged sword, predicting both higher MVPA and energy
      dense foods intake. CONCLUSION: BAS may operate in a complex manner, predicting
      behaviours which may have opposite effects on BMI.

PMID- 30288921
TI  - Unrecognized pregnancy prior to bariatric surgery: case report and review of
      implications.

PMID- 30288922
TI  - Draft genomes and genomic divergence of two Lepidurus tadpole shrimp species
      (Crustacea, Branchiopoda, Notostraca).
AB  - Crustaceans of the order Notostraca (Branchiopoda) are distributed worldwide and
      are known for the remarkable morphological stasis between their extant and
      Permian fossil species. Moreover, these crustaceans show relevant ecological
      traits and a wide range of reproductive strategies. However, genomic studies on
      notostracans are fairly limited. Here, we present the genome sequences of two
      notostracan taxa, Lepidurus arcticus and Lepidurus apus lubbocki. Taking
      advantage of the small genome sizes (~0.11 pg) of these taxa, genomes were
      sequenced for one individual per species with one run on the Illumina HiSeq X
      platform. We finally assembled 73.2 Mbp (L. arcticus) and 90.3 Mbp (L. apus
      lubbocki) long genomes. Assemblies cover up to 84% of the estimated genome size,
      with a gene completeness >97% for both genomes. In total, 13%-16% of the
      assembled genomes consist of repeats, and based on read mapping, L. apus lubbocki
      shows a significantly lower transposable element content than L. arcticus. The
      analysis of 2,376 orthologous genes indicates an ~7% divergence between the two
      Lepidurus taxa, with a nucleotide substitution rate significantly lower than that
      of Daphnia taxa. Ka /Ks analysis suggests purifying selection in both branchiopod
      lineages, raising the question of whether the low substitution rate of Lepidurus
      is correlated with morphological conservation or is linked to specific biological
      traits. Our analysis demonstrates that, in these organisms, it is possible to
      obtain high-quality draft genomes from single individuals with a relatively low
      sequencing effort. This result makes Lepidurus and Notostraca interesting models
      for genomic studies at taxonomic, ecological and evolutionary levels.

PMID- 30288923
TI  - Influence of glaucoma surgery on visual function: a clinical cohort study and
      meta-analysis.
AB  - PURPOSE: To determine the cost (loss of visual function associated with the
      procedure) and benefit (long-term preservation of the visual field) of glaucoma
      surgery. METHODS: We included 100 patients who underwent glaucoma surgery
      (Baerveldt glaucoma implant [BGI], n = 61; trabeculectomy [TE], n = 39).
      Preoperatively, the median (interquartile range [IQR]) standard automated
      perimetry mean deviation (MD) was -12 (-16 to -6) dB. We analysed the change in
      visual acuity (BCVA) and MD due to the procedure and, in a subset with at least 5
      years of perimetric follow-up both pre- and postoperatively (n = 20), the change
      in rate of progression (ROP; time rate of change in MD). For the surgery-induced
      change in ROP, we also performed a meta-analysis including the current and
      previously published studies. From the surgery-induced decrease in MD and change
      in ROP, we calculated the average postoperative duration needed for the benefit
      to surpass the cost. RESULTS: Mean (standard deviation) MD decline was 1.3 (2.7)
      and 1.0 (2.3) dB for BGI (p < 0.001) and TE (p = 0.009), respectively; no
      significant surgery-induced changes in BCVA were found (p = 0.08 and p = 0.12,
      respectively). In our study, surgery was associated with a non-significant
      deceleration of ROP (from -0.37 [0.52] to -0.15 [0.48] dB/year; p = 0.23). The
      meta-analysis, based on eight studies, showed an overall surgery-induced change
      in ROP of 0.44 (95% confidence interval 0.25 to 0.64; p < 0.0001) dB/year.
      CONCLUSION: Glaucoma surgery significantly reduces the progression velocity in
      glaucoma. On average, the benefit of glaucoma surgery surpasses the cost after
      approximately 1.5 years.

PMID- 30288924
TI  - An interview with David L. Streiner: Truth teller of statistical concepts in
      medicine.

PMID- 30288925
TI  - Atrial flutter, time to acknowledge its own identity.

PMID- 30288926
TI  - Influence of seasons upon personal light exposure and longitudinal axial length
      changes in young adults.
AB  - PURPOSE: To investigate the association between objectively measured ambient
      light exposure and longitudinal axial length changes (and their seasonal
      variations) over a period of 12 months in young adults. METHODS: This prospective
      longitudinal observational study included 43 healthy young adult university
      students (21 emmetropes and 22 myopes) aged between 18 and 30 years. Three axial
      length measurements were collected at 6-month intervals (i.e. at baseline, 6 and
      12 months), in summer and winter to determine the axial eye growth. Personal
      ambient light exposure data were measured in winter and summer months with
      wearable sensors, from which the mean daily time exposed to bright (outdoor)
      light levels (>1000 lux) was derived. RESULTS: Greater daily bright light
      exposure was associated with less axial eye growth (beta = -0.002, p = 0.006)
      over 12 months. In summer, myopes exhibited significantly greater changes in
      axial length (mean change 0.04 +/- 0.05 mm) compared to emmetropes (-0.01 +/-
      0.05 mm) (p = 0.001), but there was no significant difference between refractive
      groups in winter. Emmetropes also spent significantly greater time in outdoor
      light levels in summer compared to winter (p < 0.0001), while myopes spent
      similar time outdoors during both seasons (p = 0.12). Differences in light
      exposure between summer and winter were also associated with seasonal differences
      in axial eye growth (p = 0.026). CONCLUSION: In young adults, greater time spent
      in bright light was associated with slower longitudinal axial eye growth.
      Seasonal light exposure and axial length changes were dependent on refractive
      error in this population and also exhibited an inverse relationship.

PMID- 30288927
TI  - Inhibition of F1 -ATPase from Trypanosoma brucei by its regulatory protein
      inhibitor TbIF1.
AB  - Hydrolysis of ATP by the mitochondrial F-ATPase is inhibited by a protein called
      IF1 . In the parasitic flagellate, Trypanosoma brucei, this protein, known as
      TbIF1 , is expressed exclusively in the procyclic stage, where the F-ATPase is
      synthesizing ATP. In the bloodstream stage, where TbIF1 is absent, the F-ATPase
      hydrolyzes ATP made by glycolysis and compensates for the absence of a proton
      pumping respiratory chain by translocating protons into the intermembrane space,
      thereby maintaining the essential mitochondrial membrane potential. We have
      defined regions and amino acid residues of TbIF1 that are required for its
      inhibitory activity by analyzing the binding of several modified recombinant
      inhibitors to F1 -ATPase isolated from the procyclic stage of T. brucei. Kinetic
      measurements revealed that the C-terminal portion of TbIF1 facilitates
      homodimerization, but it is not required for the inhibitory activity, similar to
      the bovine and yeast orthologs. However, in contrast to bovine IF1 , the
      inhibitory capacity of the C-terminally truncated TbIF1 diminishes with
      decreasing pH, similar to full length TbIF1 . This effect does not involve the
      dimerization of active dimers to form inactive tetramers. Over a wide pH range,
      the full length and C-terminally truncated TbIF1 form dimers and monomers,
      respectively. TbIF1 has no effect on bovine F1 -ATPase, and this difference in
      the mechanism of regulation of the F-ATPase between the host and the parasite
      could be exploited in the design of drugs to combat human and animal African
      trypanosomiases.

PMID- 30288928
TI  - Raw regulates glial population of the eye imaginal disc.
AB  - Glia are critical for proper development, support, and function of the nervous
      system. The Drosophila eye has proven an excellent model for gaining significant
      insight into the molecular mechanisms regulating glial development and function.
      Recent studies have demonstrated that Raw is required in glia of the central and
      peripheral nervous systems; however, the function of Raw in glia of the
      developing eye has not been explored. These studies demonstrate that raw
      knockdown results in a reduction in the number of glia in the third instar eye
      imaginal disc and reduced glial spreading across the field of differentiating
      photoreceptor neurons. Expression of a raw enhancer trap reveals that raw is
      expressed in eye disc glia. Exploration of the mechanism by which raw knockdown
      results in glial reduction reveals that Raw is required for glial proliferation
      and migration into the eye disc. In addition, Raw negatively regulates Jun N
      terminal kinase (JNK) signaling in glia of the developing eye and increased JNK
      signaling results in a reduction in the number of glia populating the eye disc,
      similar to that observed upon raw knockdown. Thus, Raw functions as a critical
      regulator of glial population of the eye imaginal disc by regulating glial
      proliferation and migration and inhibiting JNK signaling.

PMID- 30288929
TI  - Emerging data and future directions for CDK4/6 inhibitor treatment of patients
      with hormone receptor positive HER2-non-amplified metastatic breast cancer.
AB  - Cyclin-dependent kinase (CDK4/6) inhibitors in combination with endocrine therapy
      are currently the optimal first line treatment for hormone receptor (HR)
      positive, human epidermal growth factor receptor 2 (HER2) non-amplified
      metastatic breast cancer (MBC). However, not all patients benefit from this
      treatment and all patients will inevitably progress. Identifying therapeutic
      strategies in this setting is therefore of immediate clinical importance. We
      present an overview of the mechanisms of resistance to CDK4/6 inhibitors and
      review potential biomarkers that may guide therapy selection. We also discuss the
      use of CDK4/6 inhibitors in the context of non-HR-positive/HER2-non-amplified
      breast cancer and in combination with therapies other than endocrine therapy.

PMID- 30288930
TI  - Hormone receptor positive, HER2 negative metastatic breast cancer: Impact of
      CDK4/6 inhibitors on the current treatment paradigm.
AB  - Resistance to endocrine therapy is a significant therapeutic challenge in the
      treatment of women with hormone receptor positive (HR+), human epidermal growth
      factor receptor 2 negative (HER2-) advanced breast cancer. Cyclin-dependent
      kinase (CDK)4/6 inhibitors in combination with endocrine therapy have been shown
      to improve progression free survival, overall response rate and clinical benefit
      rate in women with HR+ HER2- metastatic breast cancer compared with endocrine
      therapy alone. This review examines the clinical evidence to support the use of
      CDK4/6 inhibitors in first and second line settings. Practical guidance is
      provided for the use of CDK4/6 inhibitors, including tolerability data,
      monitoring requirements and management of key toxicities for each of the
      available agents.

PMID- 30288931
TI  - Ion- and Electron-Conductive Buffering Layer-Modified Si Film for Use as a High
      Rate Long-Term Lithium-Ion Battery Anode.
AB  - The rational design of electrochemically and mechanically stable Si anodes is of
      great importance for the development of high energy density lithium-ion
      batteries. In this study, patterned Si-based (Si/ZnO/C) trilayer composite films
      were synthesized by magnetron sputtering with the assistance of a patterned mask.
      The electron-conductive C layer at the top of the composite film is deposited to
      enhance the interfacial stability between active film and electrolyte. The ion-
      and electron-conductive Li2 O-Zn middle layer can be ingeniously introduced by
      means of the poor reversed conversion reaction between ZnO and Li+ ions after the
      first cycle. The resultant Si/Li2 O-Zn/C trilayer composite film delivers a high
      reversible capacity of 1536 mAh g-1 after 800 cycles at a current density of 1.0
      A g-1 and a long high-rate cycling stability (1400 mAh g-1 after 6000 cycles even
      at a high current density of 10.0 A g-1 ). Excellent rate capability and improved
      Coulombic efficiency are also achieved. The influences of the patterned structure
      and each modified layer on the electrochemical properties are analyzed
      systematically. This work offers a new and promising direction to enhance the
      lithium-storage properties of Si-based thin-film anodes.

PMID- 30288932
TI  - The Neuropeptide Secretoneurin Exerts a Direct Effect on Arteriogenesis In Vivo
      and In Vitro.
AB  - It is well known that nerves modulate the development and remodeling of blood
      vessels by releasing different neuropeptides and neurotransmitters. Secretoneurin
      (SN), a neuropeptide located in nerve fibers along blood vessels, acts as a pro
      angiogenic agent and induces postnatal vasculogenesis. However, little is known
      about its involvement in arteriogenesis. In the present study, we tested the
      hypothesis that SN promotes arteriogenesis in a rat model of hind limb ischemia,
      as such, we evaluated the effect of this neuropeptide on proliferation and the
      production of adhesion and chemotaxis molecules in vascular smooth muscle cells
      (VSMCs), the main component that carries the burden of the transformation of a
      small arteriole into a large collateral vessel. In vivo, SN-immunoreactive nerve
      fibers were abundantly distributed in the adventitia of the collateral vessel.
      Moreover, administration of SN induced cell proliferation in the vascular wall
      and the infiltration of inflammatory cells/macrophages to promote collateral
      vessel growth. This was shown by an increased density of arterioles/arteries,
      together with a well-developed network of collateral vessels, and well-preserved
      skeletal muscles. In vitro, SN exerted proliferative effects on VSMCs and
      stimulated these cells to express adhesion molecules. In conclusion, our data
      demonstrate for the first time that SN acts as a mediator of inflammation,
      contributing to collateral vessel growth, in addition to directly stimulating
      cell proliferation in the vascular wall to promote collateral vessel growth in a
      rat model of hind limb ischemia. Anat Rec, 301:1917-1927, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30288933
TI  - Non-human primates as a reservoir for rabies virus in Brazil.
AB  - Rabies virus (RABV) does not persist in the environment as it is a very fragile
      agent. The primary hosts are mammalian species in the orders Carnivora and
      Chiroptera. Since the late 1980s, RABV has been isolated from non-human primates,
      Callithrix jacchus (the white-tufted marmoset), in four coastal states (Rio
      Grande do Norte, Ceara, Piaui and Pernambuco) in north-eastern Brazil, where this
      species is indigenous. The original habitat of C. jacchus consisted of two
      Brazilian biomes, the Atlantic Forest and the Caatinga. However, these marmosets
      have since adapted to other ecosystems as a result of human activities. Between
      1988 and 1989, RABV isolates were obtained from white-tufted marmosets in the
      state of Rio Grande do Norte, but antigenic and genetic identification studies
      were not conducted at that time. In the following years, three additional states
      reported cases (Ceara, Piaui and Pernambuco). In two of these states (Ceara and
      Piaui), human cases of rabies transmitted by marmosets were reported. According
      to Brazilian Health Ministry data, at least 19 human cases in which this species
      was the source of infection were registered in between 1990 and 2016. Recent
      findings in laboratory tests of 12 rabid samples from humans and marmosets and
      the regional transmission among these animals for over 20 years, together with
      the gradual increase in the affected geographic area, support the concept of the
      emergence of a new RABV reservoir. Regional tourism, the wild animal trade and
      the cultural practice of maintaining these animals as pets, particularly in
      coastal regions, appear to be major risk factors for the increase in human cases.
      Additional epidemiological and ecological studies are required to better
      understand local disease dynamics and to identify ideal opportunities for
      prevention and control of this fatal infection.

PMID- 30288934
TI  - Rapid determination of anticoagulating effects of dabigatran in whole blood with
      rotational thromboelastometry and a thrombin-based trigger.
AB  - Essentials A rapid test to detect thrombin inhibition by dabigatran would be
      valuable in acute situations. A thrombin-based trigger was applied in whole blood
      using rotation thromboelastometry. Effects of dabigatran were assessed in vitro
      and in samples from patients on dabigatran. The test produced data rapidly and
      was sensitive to dabigatran concentrations from 20 to 500 ng mL-1 . SUMMARY:
      Background Rapid determination of the anticoagulant effect of dabigatran is
      essential in emergency situations. Objective To study a viscoelastic test
      (rotational thromboelastometry [ROTEM]) for rapid determination of dabigatran
      effects in whole blood samples. Method ROTEM measurements were performed with
      comparison of two triggers (thrombin-based versus the commercial tissue factor
      based trigger Ex-tem) in samples from 10 healthy donors spiked with dabigatran
      (20-500 ng mL-1 ) and in samples from 35 patients receiving dabigatran treatment;
      10 healthy subjects served as controls. Clotting time (CT) and the difference in
      CT without versus with addition of the dabigatran antidote idarucizumab (CTdiff )
      were measured. Addition of idarucizumab reveals the contribution of dabigatran to
      ROTEM measurements and its potential reversibility. Results In vitro studies
      showed that thrombin CT and thrombin CTdiff were more sensitive than Ex-tem CT
      and Ex-tem CTdiff in detecting dabigatran in whole blood samples. In patient
      samples, when thrombin CT and thrombin CTdiff were used, it was possible to
      detect dabigatran with a cut-off of dabigatran at 20 ng mL-1 , whereas, when Ex
      tem CT and Ex-tem CTdiff were used, the method was less sensitive. Data from
      patient samples were obtained within 15 min of blood sampling. Conclusions ROTEM
      CT with a thrombin-based trigger is more sensitive to dabigatran effects than Ex
      tem CT, and detects anticoagulant effects of drug concentrations in the low-very
      low therapeutic range. Analysis with idarucizumab (CTdiff ) reveals dabigatran
      specific effects. As data are rapidly obtained, this method could, with further
      development and validation of its performance, be suitable for detecting
      clinically significant dabigatran effects in emergency situations.

PMID- 30288935
TI  - Defining specific residue-to-residue interactions between the gp120 bridging
      sheet and the N-terminal segment of CCR5: applications of transferred NOE NMR.
AB  - Infection by HIV-1 requires protein-protein interactions involving gp120, CD4 and
      CCR5. We have previously demonstrated that the transferred nuclear Overhauser
      effect (TRNOE), in combination with asymmetric deuteration of a protein and a
      peptide ligand can be used to detect intermolecular interactions in large protein
      complexes with molecular weights up to ~ 100 kDa. Here, using this approach, we
      reveal interactions between tyrosine residues of a 27-residue peptide
      corresponding to the N-terminal segment of the CCR5 chemokine receptor, and a
      dimeric extended core YU 2 gp120 envelope protein of HIV-1 complexed with a CD4
      mimic miniprotein. The TRNOE crosspeaks in the ternary complex were assigned to
      the specific Tyr protons in the CCR5 peptide and to methyl protons of isoleucine,
      leucine and/or valine residues of gp120. Site directed mutagenesis combined with
      selective deuteration and TRNOE resulted in the first discernment by a
      biophysical method of specific pairwise interactions between gp120 residues in
      the bridging sheet of gp120 and the N-terminus of CCR5.

PMID- 30288936
TI  - GammaKnife versus VMAT radiosurgery plan quality for many brain metastases.
AB  - The purpose of this work was to compare dose distributions between two
      radiosurgery modalities, single-isocenter volumetric modulated arc therapy
      (VMAT), and GammaKnife Perfexion (GK), in the treatment of a large number (>=7)
      of brain metastases. Twelve patients with 103 brain metastases were analyzed. The
      median number of targets per patient was 8 (range: 7-14). GK plans were compared
      to noncoplanar VMAT plans using both 6-MV flattening filter-free (FFF) and 10-MV
      FFF modes. Parameters analyzed included radiation therapy oncology group
      conformity index (CI), 12, 6, and 3 Gy isodose volumes (V12 Gy, V6 Gy, V3 Gy),
      mean and maximum hippocampal dose, and maximum skin dose. There were
      statistically significant differences in CI (2.5 +/- 1.6 vs 1.6 +/- 0.8 and 1.7
      +/- 0.9, P < 0.001, P < 0.001), V12 Gy (2.8 +/- 6.1 cc vs 3.0 +/- 5.2 cc and 3.1
      +/- 5.4 cc, P = 0.003, P < 0.001), and V3 Gy (323.0 +/- 294.8 cc vs, 880.1 +/-
      369.1 cc and 937.9 +/-  vs 361.9 cc, P = 0.005, P = 0.001) between GK versus both
      6-MV FFF and 10-MV FFF. No significant differences existed for maximum
      hippocampal or skin doses. In conclusion, highly optimized VMAT produced improved
      conformity at the expense of a higher V12 Gy and V3 Gy volume when compared with
      highly optimized GK.

PMID- 30288937
TI  - The effects of endogenous and exogenous catecholamines on hypoxic cardiac
      performance in red-bellied piranhas.
AB  - Catecholamines protect the fish heart during hypoxia. However, the humoral
      adrenergic stress response may only be invoked in extremis. We investigated the
      hypothesis that endogenous (e.g., neuronal) myocardial catecholamines may also
      impact cardiac performance during hypoxia in a hypoxia-tolerant tropical fish,
      the red-bellied piranha (Pygocentrus nattereri). First, we measured endogenous
      tissue catecholamines and in vitro catecholamine release from piranha myocardium
      using ultraperformance liquid chromatography. Ventricle homogenates contained
      detectable levels of both adrenaline (7.27 ng/g) and noradrenaline (14.48 ng/g),
      but only noradrenaline was released from ventricular tissue incubated in Ringer's
      solution. Noradrenaline released in this assay was not affected by hypoxia but
      was promoted by the catecholamine releasing agent tyramine. Our second series of
      experiments explored cardiac contractile performance in vitro using tyramine,
      exogenous noradrenaline or adrenaline, and propranolol (a beta-adrenoceptor
      antagonist). In ventricular strip preparations, beta-adrenergic blockade with
      propranolol had no effects on twitch force or contraction kinetics in either
      normoxia or hypoxia, confirming that spontaneous endogenous catecholamine release
      did not impact cardiac performance. However, in the absence of propranolol,
      tyramine mimicked the positive inotropic effect of noradrenaline (10 uM) during
      hypoxia, although adrenaline was capable of generating larger effects. Our
      results suggest that, although it is not spontaneously released, inducible
      endogenous noradrenaline release may have a significant beta-adrenoceptor
      dependent impact on hypoxic performance in the fish heart.

PMID- 30288938
TI  - Clinical outcomes among morbidly obese patients hospitalized with diabetic foot
      complications.
AB  - The aim of the study is to investigate effects of morbid obesity on patients
      hospitalized with diabetic foot ulcers and infections (DFU/Is). This
      retrospective cohort study of hospitalized adults investigated patients with a
      principal diagnosis of DFU/Is, and compared outcomes based on weight. The primary
      outcome was lower limb amputations. Secondary outcomes included in-hospital
      mortality, morbidity (sepsis and discharge disposition), resource utilization
      (length of stay [LOS] and total hospitalization charges). Multivariate analyses
      adjusted for confounders. A total of 31 730 admissions were included; 14% were
      morbidly obese. Patients with morbid obesity had overall lower rates of
      amputations (adjusted odds ratio [aOR]: 0.60; 95% confidence interval [CI]: 0.45
      0.80). There was no difference in mortality rates between those who were morbidly
      obese and the non-morbidly obese patients (aOR: 3.89 [95% CI: 0.79-19.30]).
      Combined data from 2010 to 2014 have found higher odds of sepsis in morbidly
      obese patients compared with non-morbidly obese patients after adjusting for
      confounders (aOR: 1.49 [1.09-2.02], P = 0.01). Patients with morbid obesity were
      less likely to be discharged to home (aOR: 0.82 [95% CI: 0.70-0.95]), had longer
      LOS (adjusted mean difference [aMD]: 0.47 [95% CI: 0.13-0.81]) and higher
      hospital charges (aMD: $3205 [95% CI: $3373-$6037]). Despite having lower
      amputation rates compared to those who are not morbidly obese, patients with
      morbid obesity hospitalized for DFU/Is succumbed to sepsis more frequently and
      had less favourable utilization metrics. Specialized care pathways may be needed
      to enhance the value of care delivered to this high-risk population.

PMID- 30288939
TI  - Change in subfoveal choroidal thickness secondary to orthokeratology and its
      cessation: a predictor for the change in axial length.
AB  - PURPOSE: To investigate changes in subfoveal choroidal thickness (SFChT) during
      orthokeratology (Ortho-K) lens wear and after its cessation and the association
      of short-term change in SFChT with the long-term eye elongation in Ortho-K
      subjects. DESIGN: A prospective clinical trial. METHODS: Fifty myopic children
      aged between 9 and 14 years were enrolled. Twenty-nine subjects continuously wore
      Ortho-K lens for 12 months and discontinued for 1 month. Twenty-one subjects
      wearing single vision distance spectacles for 12 months were included as the
      control group. SFChT was assessed using optical coherence tomography. Ocular
      parameters, including axial length (AL), central corneal thickness (CCT),
      anterior chamber depth (ACD), lens thickness (LT) and apical corneal power (ACP),
      were also measured. RESULTS: After 12 months of follow-up, AL elongation was
      larger and SFChT change was smaller in the control group compared to the Ortho-K
      group (both p < 0.001). In the Ortho-K group, SFChT increased by 16 MUm from
      baseline at the 1-month visit (p < 0.001), and the magnitude of choroidal
      thickening remained unchanged at the 6- and 12-month visit (p = 0.289). One month
      after discontinuation of Ortho-K lens, SFChT and ocular parameters of the
      anterior segment, including ACP, CCT and ACD recovered to baseline level (All p >
      0.05), and AL increased by 0.23 +/- 0.18 mm compared to baseline (p = 0.018).
      SFChT change at 1-month was negatively associated with AL change at 13-month
      (standard beta, -0.581, p = 0.001) after adjusting for other influencing factors,
      including baseline age and the ocular parameters. CONCLUSION: Subfoveal ChT
      (SFChT) significantly increased after short-term Ortho-K lens treatment and the
      increase maintained throughout the period of treatment. One month after Ortho-K
      lens cessation, SFChT, ACP, CCT and ACD returned to baseline. Short-term response
      in SFChT is associated with long-term change in AL in children undergoing Ortho-K
      lens and may be a predictor for the effectiveness of the treatment.

PMID- 30288940
TI  - A Direct Approach for Process Development Using Single Column Experiments Results
      in Predictable Streamlined Multi-Column Chromatography Bioprocesses.
AB  - An emphasis on continuous monoclonal antibody (mAb) bioprocessing in the
      pharmaceutical industry necessitates effective approaches for downstream process
      development (PD). With a PD strategy, the process parameters are optimized to
      directly develop streamlined three-step continuous chromatography processes. A
      design of experiment (DoE) approach with single column (batch mode) is used to
      simulate a multi-column (continuous mode) purification method and characterize
      each chromatography step: Protein A capture, anion exchange, and mixed mode
      cation exchange. A novel and targeted approach to quickly characterize a DoE
      design space was employed and empirical modeling was used to define the capacity
      for multi-column chromatography to accurately transfer the batch process to
      continuous mode of purification. This PD approach effectively mimics the
      continuous mode of operation and provides the flexibility to develop multiple
      continuous processes with target mAb recovery and purity. By implementing this PD
      strategy and the process parameters defined in batch mode, two robust and
      predictable continuous bioprocesses were developed within 7 weeks of
      investigation, which resulted in a total product yield of recovery at or above
      74%, host cell protein (HCP) content below 5 ppm, and aggregate content below 1%.

PMID- 30288942
TI  - Continuing Professional Development.

PMID- 30288941
TI  - Trans Tasman Radiation Oncology Group Cancer Research: Phase III - Muscle
      Invasive Bladder Cancer trial (TROG 02.03): A moral dilemma.

PMID- 30288943
TI  - Are we suffering from burnout and if so what next?

PMID- 30288944
TI  - cOAlition S troubles top journals.

PMID- 30288945
TI  - Anatomic Studies of the Miniature Swine Cornea.
AB  - The domestic swine eye resembles the human eye both anatomically and
      physiologically. Xenotransplantation of the swine cornea to humans in need of
      full keratoplasty shows promise as a potential therapeutic strategy to restore
      vision in individuals with advanced corneal disease, especially those residing in
      developing nations. That said, we characterized the morphology of corneas from
      miniature swine, which are smaller in size, easier to handle, and more cost
      effective compared to domestic swine. Eyes (N = 15) were harvested from miniature
      swine from different age groups: 1 month (N = 3), 2 month (N = 3), 4 month (N =
      3), 8 month (N = 3), as well as 24 month old adult domestic swine (N = 3). They
      were immediately submerged in fixative and processed for histological examination
      at the light and transmission electron microscopic level. Gross anatomic
      measurements of the cornea were significantly less (P value <= 0.05) in miniature
      swine versus domestic swine. Corneal strata exhibited morphological
      characteristics similar to the domestic swine cornea. Adult miniature swine
      corneas show similar overall corneal thickness at 8 months of age versus domestic
      swine. Miniature swine exhibit similar corneal morphology with the domestic pig
      and humans, with the exception of Bowman's layer, which is absent in pigs.
      Therefore, miniature pigs may be a useful resource of corneal tissue for humans
      in need of full keratoplasty, as well as serve as a large eye model for
      ophthalmology residents to develop surgical skills and for development and
      testing of ocular therapeutic strategies that translate to humans. Anat Rec,
      301:1955-1967, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30288946
TI  - Plasma markers of chronic low-grade inflammation in polypoidal choroidal
      vasculopathy and neovascular age-related macular degeneration.
AB  - PURPOSE: Ageing is the strongest predictor of neovascular age-related macular
      degeneration (AMD), where neuroinflammation is known to play a major role. Less
      is known about polypoidal choroidal vasculopathy (PCV), which is an important
      differential diagnosis to neovascular AMD. Here, we report plasma markers of
      inflammation with age (inflammaging) in patients with PCV, patients with
      neovascular AMD and a healthy age-matched control group. METHODS: We isolated
      plasma from fresh venous blood obtained from participants (n = 90) with either
      PCV, neovascular AMD, or healthy maculae. Interleukin(IL)-1beta, IL-6, IL-8, IL
      10 and tumour necrosis factor receptor 2 (TNF-R2) were measured using U-PLEX
      Human Assays. Routine plasma C-reactive protein (CRP) was measured using
      Dimension Vista 1500. RESULTS: Patients with PCV had plasma levels of IL-1beta,
      IL-6, IL-8, IL-10 and TNF-R2 similar to that in healthy controls. Patients with
      neovascular AMD had significantly higher plasma IL-1beta, IL-6 and IL-10 than
      healthy controls, whereas no significant differences were observed for plasma IL
      8 and TNF-R2. Differences between plasma IL-1beta, IL-6 and IL-10 possessed a
      positive but weak ability in discriminating neovascular AMD from PCV. Both
      patients with PCV and patients with neovascular AMD had significantly higher
      levels of routine plasma CRP. CONCLUSION: Patients with PCV differ from patients
      with neovascular AMD in terms of plasma inflammaging profile. Apart from
      increased CRP, no signs of inflammaging were observed in patients with PCV. In
      patients with neovascular AMD, we find a specific angiogenesis-twisted
      inflammaging profile.

PMID- 30288947
TI  - Ranking the stars.

PMID- 30288948
TI  - pH/Redox-Triggered Photothermal Treatment for Cancer Therapy Based on a Dual
      Responsive Cationic Polymer Dot.
AB  - In the present study, a pH/redox-responsive cationic polymer dot (CD) was
      successfully prepared for a near-infrared (NIR)-mediated, simultaneously
      controllable photothermal temperature guided imaging off/on system to monitor
      therapeutic delivery. Carbonized disulfide cross-linked branched
      polyethyleneimine (bPEI) was conjugated with folic acid (FA) as a targeting
      moiety and partially formed an ionic complex with anionic indocyanine green (ICG)
      to afford a bPEI-based CD (ICG-CD). This was responsive to mild reductive
      (glutathione, GSH) and acidic tumor conditions, which enabled the simultaneous
      biodegradation of those hydrophobic and complex sites. The ICG-CD internalized
      readily into the cytoplasm of cancer cells by a FA receptor and cationic-mediated
      endocytosis in the off state, whereas if ICG-CD met intracellular GSH at high
      concentrations, GSH contributed partially to the recovery of fluorescence and was
      then internalized into acidic endosomes to induce complete restoration of
      fluorescence. This tumor-sensitive degradability of the CD not only facilitated
      ICG release in the tumor location but also allowed controllable photothermal
      therapy effects of nanoparticles under NIR irradiation, which resulted in
      improved cancer therapy. Taken together, the results indicate great potential in
      tumor targeting, intracellular imaging, and controllable therapeutic delivery
      through a fluorescence off/on assay under the pH/redox conditions of cancer
      cells.

PMID- 30288949
TI  - Collagen chirality and three-dimensional orientation studied with polarimetric
      second-harmonic generation microscopy.
AB  - Polarization-dependent second-harmonic generation (P-SHG) microscopy is used to
      characterize molecular nonlinear optical properties of collagen and determine a
      three-dimensional (3D) orientation map of collagen fibers within a pig tendon. C6
      symmetry is used to determine the nonlinear susceptibility tensor components
      ratios in the molecular frame of reference chizzz2/chizxx2 and chixyz2/chizxx2 ,
      where the latter is a newly extracted parameter from the P-SHG images and is
      related to the chiral structure of collagen. The chixyz2/chizxx2 is observed for
      collagen fibers tilted out of the image plane, and can have positive or negative
      values, revealing the relative polarity of collagen fibers within the tissue. The
      P-SHG imaging was performed using a linear polarization-in polarization-out
      (PIPO) method on thin sections of pig tendon cut at different angles. The
      nonlinear chiral properties of collagen can be used to construct the 3D
      organization of collagen in the tissue and determine the orientation-independent
      molecular susceptibility ratios of collagen fibers in the molecular frame of
      reference.

PMID- 30288950
TI  - Imbalances in tissue inhibitors of metalloproteinases differentiate choroidal
      neovascularization from geographic atrophy.
AB  - PURPOSE: Tissue inhibitor of metalloproteinase (TIMP) is known to play a role in
      age-related macular degeneration (AMD). We wished to investigate alterations in
      different late stages of AMD: neovascular AMD and geographic atrophy (GA).
      METHODS: This was a prospective case-control study. A total of 125 participants
      were included consecutively during a period of 18 months. We included 46 patients
      with neovascular AMD, 46 patients with GA without any sign of choroidal
      neovascularization in either eye, and 33 healthy aged controls. Patients with
      immune-affecting disorders were not included. Commercial immunoassay kits were
      used to quantify levels of TIMP-1, TIMP-3, MMP-2 and MMP-9 in blood plasma.
      RESULTS: We found that patients with neovascular AMD had lower plasma
      concentration of TIMP-3 (p = 0.028) than healthy controls. Patients with GA had
      higher plasma levels of TIMP-1 (p < 0.001) and MMP-9 (p = 0.022) compared to
      healthy controls. Also, we found that TIMP-1 levels in patients with GA increased
      with age (Spearman's rho = 0.04, p = 0.006). CONCLUSION: Matrix
      metalloproteinases (MMPs) and TIMPs, which are known to be involved in age
      related changes in Bruch's membrane, are significantly altered systemically,
      suggesting the presence of an imbalance in the homeostasis of the extracellular
      matrix. These imbalances may explain differences in the clinical manifestation of
      late AMD.

PMID- 30288951
TI  - Tobacco Mosaic Virus as a Versatile Platform for Molecular Assembly and Device
      Fabrication.
AB  - Viruses are unique biological agents that infect living host cells through
      molecular delivery of a genomic cargo. Over the past two decades advancements in
      genetic engineering and bioconjugation technologies have allowed the
      unprecedented use of these "unfriendly" biological molecules, as nanoscopic
      platforms for the advancement of an array of nanotechnology applications. This
      mini-review focuses on providing a brief summary of key demonstrations leveraging
      the versatile characteristics of Tobacco mosaic virus (TMV) for molecular
      assembly and bio-device integration. A comprehensive discussion of genetic and
      chemical modification strategies along with potential limiting factors that
      impact the assembly of these macromolecules is presented to provide useful
      insights for adapting TMV as a potentially universal platform toward developing
      advanced nanomaterials. Additional discussions on biofabrication techniques
      developed in parallel to enable immobilization, alignment, and patterning of TMV
      based functional particles on solid surfaces will highlight technological
      innovations that can be widely adapted for creating nanoscopic device components
      using these engineered biomacromolecules. Further exploitation in the design of
      molecular specificity and assembly mechanisms and the development of highly
      controllable and scalable TMV-device integration strategies will expand the
      library of nanoscale engineering tools that can be used for the further
      development of virus-based nanotechnology platforms.

PMID- 30288952
TI  - Evaluating the yield of gastrointestinal testing in pediatric patients in
      aerodigestive clinic.
AB  - OBJECTIVE: To improve understanding of the interrelatedness of airway and
      esophageal diagnoses by evaluating the yield of procedural and radiographic
      testing of the gastrointestinal tract in children with airway conditions by their
      referring diagnoses in a pediatric aerodigestive clinic. METHODS: A retrospective
      chart review of all 325 patients seen in the aerodigestive program from 2010 to
      2013 was performed in a single academic medical center. Demographics and results
      from esophagogastroduodenoscopies with biopsies (EGD), upper gastrointestinal
      fluoroscopy studies (UGI), and pH multichannel intraluminal impedance probe (pH
      MII) performed within 30 days of the clinic visit were evaluated according to
      presenting diagnoses. RESULTS: Mean patient age was 3.15 years (range 0.15-24
      years) and 41.2% were born premature. 189/325 (58.1%) were on acid suppression. A
      total of 295 EGD, 193 pH-MII, and 54 UGI were performed. The most common
      diagnosis with an abnormal pH-MII was asthma. The most common diagnoses with an
      abnormal EGD were feeding difficulty and tracheal esophageal fistula/ esophageal
      atresia (TEF/EA). EGDs were normal in 188/295 (63.7%), while 39/295 (13.2%)
      demonstrated esophagitis, and 22/295 (7.5%) had >15 esophageal eosinophils per
      high power field. The majority of pH-MII (144/193 [74.6%]) and UGI (47/54 [87%])
      were normal. CONCLUSIONS: Children with feeding difficulty, TEF/EA, and asthma
      were the mostly likely to have a histologic abnormality on EGD or an abnormal pH
      MII. The majority of children were previously prescribed acid suppression
      medication and had a referring diagnosis of gastroesophageal reflux disease but
      were subsequently found to have normal evaluation. Prospective studies are needed
      to optimize care of this population.

PMID- 30288953
TI  - Hand Factors in Cardiac Development.
AB  - Congenital heart defects account for 1% of infant mortality and 10% of in utero
      deaths. As the vertebrate embryo develops, multiple tissue types develop in
      tandem to morphologically pattern the functional heart. Underlying cardiac
      development is a network of transcription factors known to tightly control these
      morphological events. Members of the Twist family of basic helix-loop-helix
      transcription factors, Hand1 and Hand2, are essential to this process. The
      expression patterns and functional role of Hand factors in neural crest cells,
      endocardium, myocardium, and epicardium is indicative of their importance during
      cardiogenesis; however, to date, an extensive understanding of the
      transcriptional targets of Hand proteins and their overall mechanism of action
      remain unclear. In this review, we summarize the recent findings that further
      outline the crucial functions of Hand factors during heart development and in
      post-natal heart function. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30288954
TI  - A repeated cross-sectional study of the epidemiology of Campylobacter and
      antimicrobial resistant Enterobacteriaceae in free-living Canada geese in Guelph,
      Ontario, Canada.
AB  - From May through October 2016, we conducted a repeated cross-sectional study
      examining the effects of temporal, spatial, flock and demographic factors (i.e.
      juvenile vs. adult) on the prevalence of Campylobacter and antimicrobial
      resistant Enterobacteriaceae among 344 fresh faecal samples collected from Canada
      geese (Branta canadensis) from four locations where birds nested in Guelph,
      Ontario, Canada. The overall prevalence of Campylobacter among all fresh faecal
      samples was 9.3% and was greatest in the fall when these birds became more mobile
      following the nesting season. Based on 40 gene comparative genomic fingerprinting
      (CGF40), the increase in prevalence noted in the fall was matched by an increase
      in the number of unique CGF40 subtypes identified. Resistance to colistin was
      detected most commonly, in 6% of Escherichia coli isolates, and was highest in
      the late summer months. All colistin-resistant isolates were negative for the mcr
      1 to mcr-5 genes; a chromosomal resistance mechanism (PmrB) was identified in all
      of these isolates. The prevalence of samples with E. coli exhibiting multi-class
      resistance or extended spectrum beta-lactamase was low (i.e. <2% of samples). The
      intra-class correlation coefficients, estimated from the variance components of
      multilevel logistic regression models, indicated that the shedding of
      Campylobacter and antimicrobial resistant E. coli among geese within a flock
      (i.e. birds collected from the same site on the same day) was moderately
      correlated. Spatial, temporal, and spatiotemporal clusters identified using the
      spatial scan statistic, largely supported the findings from our multi-level
      models. Salmonella was not isolated from any of the fresh faecal samples
      collected suggesting that its prevalence in this population of birds was very
      low.

PMID- 30288956
TI  - Adaptive Anatomical Specialization of the Intestines of Alpacas Taking into
      Account their Original Habitat and Feeding Behaviour.
AB  - The gastrointestinal tract of the alpaca (Vicugna pacos) is most efficiently
      adapted to its habitat at high altitudes. Alpacas, just like ruminants, feed on
      hardly digestible forage. However, it has been demonstrated that the anatomy of
      the camelid digestive tract has developed independently of ruminants and not in
      homology to them. Despite a long history of domestication and an increasing
      number of animals worldwide, little research has been done on the intestinal
      anatomy of alpacas. The purpose of this study was to describe the anatomical
      features of the alpaca's intestines and to explain anatomical peculiarities in
      the context of evolutionary function and morphology. Another goal of this study
      was the demonstration of weaknesses of the intestinal anatomy predisposing
      alpacas to certain clinical presentations. Six animals were used for dissection.
      The basic structure of the intestines was comparable to that in ruminants.
      However, a number of characteristic peculiarities were found in alpacas, like the
      duodenal ampulla and the proximal and distal loop of the ascending colon. The
      jejunum and ileum, unlike those of ruminants, had their own mesentery largely
      separated from the ascending mesocolon. The main blood supply was provided by the
      cranial and caudal mesenteric artery. The particular lymph nodes were located
      along the branches of these two arteries. The spiral colon seemed to play a major
      role in intestinal digestion and water resorption. The size of the distal
      fermentation chamber allows the presumption that alpacas belong to the group of
      animals practicing a fractionated fermentation in the proximal and distal
      fermentation chambers. Anat Rec, 301:1840-1851, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 30288955
TI  - Development of the Myocardial Interstitium.
AB  - The space between cardiac myocytes is commonly referred-to as the cardiac
      interstitium (CI). The CI is a unique, complex and dynamic microenvironment in
      which multiple cell types, extracellular matrix molecules, and instructive
      signals interact to crucially support heart homeostasis and promote cardiac
      responses to normal and pathologic stimuli. Despite the biomedical and clinical
      relevance of the CI, its detailed cellular structure remains to be elucidated. In
      this review, we will dissect the organization of the cardiac interstitium by
      following its changing cellular and molecular composition from embryonic
      developmental stages to adulthood, providing a systematic analysis of the
      biological components of the CI. The main goal of this review is to contribute to
      our understanding of the CI roles in health and disease. Anat Rec, 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 30288957
TI  - Filamin-A as a Balance between Erk/Smad Activities during Cardiac Valve
      Development.
AB  - Mitral valve prolapse (MVP) affects 2.4% of the population and has poorly
      understood etiology. Recent genetic studies have begun to unravel the
      complexities of MVP and through these efforts, mutations in the FLNA (Filamin-A)
      gene were identified as disease causing. Our in vivo and in vitro studies have
      validated these genetic findings and have revealed FLNA as a central regulator of
      valve morphogenesis. The mechanisms by which FLNA mutations result in myxomatous
      mitral valve disease are currently unknown, but may involve proteins previously
      associated with mutated regions of the FLNA protein, such as the small GTPase
      signaling protein, R-Ras. Herein, we report that Filamin-A is required for R-Ras
      expression and activation of the Ras-Mek-Erk pathway. Loss of the Ras/Erk pathway
      correlated with hyperactivation of pSmad2/3, increased extracellular matrix (ECM)
      production and enlarged mitral valves. Analyses of integrin receptors in the
      mitral valve revealed that Filamin-A was required for beta1-integrin expression
      and provided a potential mechanism for impaired ECM compaction and valve
      enlargement. Our data support Filamin-A as a protein that regulates the balance
      between Erk and Smad activation and an inability of Filamin-A deficient valve
      interstitial cells to effectively remodel the increased ECM production through a
      beta1-integrin mechanism. As a consequence, loss of Filamin-A function results in
      increased ECM production and generation of a myxomatous phenotype characterized
      by improperly compacted mitral valve tissue. Anat Rec, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30288958
TI  - Heart Anatomy of Rhincodon typus: Three-Dimensional X-Ray Computed Tomography of
      Plastinated Specimens.
AB  - In this study, we examined the structure of the heart of the whale shark,
      Rhincodon typus, using a plastination technique and three-dimensional X-ray
      computer tomography (3DCT). Inspection of the atrium revealed a symmetric
      distribution of the pectinate muscles attached to the commissures of the sino
      atrial valve, suggesting some functional advantages. The majority of the
      ventricular wall comprised spongiosa, and compacta accounted for only ~3% of the
      entire thickness. There were three major fiber orientations in the spongiosa: the
      fibers on the endocardial side formed trabeculae that were aligned with the blood
      flow tract, whereas those on the epicardial side formed a circular pattern around
      the flow tract. Transmural myofibers connected the inner and outer layers in the
      spongiosa, which may serve as an intraventricular conduction pathway.
      Plastination and 3DCT is a powerful combination that allowed for multifaceted
      visualization of the internal structure of rare heart specimens in a
      nondestructive manner. Anat Rec, 301:1801-1808, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 30288959
TI  - Linear and nonlinear optical effects in biophotonic structures using classical
      and nonclassical light.
AB  - In this perspective article, we review the optical study of different biophotonic
      geometries and biological structures using classical light in linear and
      nonlinear regime, especially highlighting the link between these morphologies and
      modern biomedical research. Additionally, the importance of nonlinear optical
      study in biological research, beyond traditional cell imaging is also highlighted
      and described. Finally, we present a short introduction regarding nonclassical
      light and describe the new future perspective of quantum optical study in
      biology, revealing the link between quantum realm and biological research.

PMID- 30288960
TI  - Light at night affects hippocampal and nidopallial cytoarchitecture: Implication
      for impairment of brain function in diurnal corvids.
AB  - Our previous studies have shown that light at night (LAN) impaired cognitive
      performance and affected neurogenesis and neurochemistry in the cognition
      associated brain regions, particularly the hippocampus (HP) and lateral caudal
      nidopallium (NCL) of Indian house crows (Corvus splendens). Here, we examined the
      cytoarchitecture and mapped out the morphology of neurons and glia-neuron density
      in HP and NCL regions of crows that were first entrained to 12-hr light (LL): 12
      hr darkness (LD) and then exposed to the light regime in which 12-hr darkness was
      either replaced by daytime light (i.e., constant light, LL) or by dim light
      (i.e., dim light at night, dLAN), with controls continued on LD 12:12. Compared
      with LD, there was a significant decrease in the soma size, suggesting reduced
      neuronal plasticity without affecting the neuronal density of both HP and NCL of
      crows under LL and dLAN conditions. In parallel, we found a reduced number of
      glia cells and, hence, decreased glia-neuron ratio positively correlated with
      soma size in both, HP and NCL regions. These results for the first time
      demonstrate LAN-induced negative effects on the brain cytoarchitecture of a
      diurnal species and give insight for possible influence on the brain health and
      functions in animals including humans that might be inadvertently exposed to LAN
      in an emerging night-illuminated urban environment.

PMID- 30288961
TI  - Muscle-specific Perilipin2 down-regulation affects lipid metabolism and induces
      myofiber hypertrophy.
AB  - BACKGROUND: Perilipin2 (Plin2) belongs to a family of five highly conserved
      proteins, known for their role in lipid storage. Recent data indicate that Plin2
      has an important function in cell metabolism and is involved in several human
      pathologies, including liver steatosis and Type II diabetes. An association
      between Plin2 and lower muscle mass and strength has been found in elderly and
      inactive people, but its function in skeletal muscle is still unclear. Here, we
      addressed the role of Plin2 in adult muscle by gain and loss of function
      experiments. METHODS: By mean of in vivo Plin2 down-regulation (shPlin2) and
      overexpression (overPlin2) in murine tibialis anterior muscle, we analysed the
      effects of Plin2 genetic manipulations on myofiber size and lipid composition. An
      analysis of skeletal muscle lipid composition was also performed in vastus
      lateralis samples from young and old patients undergoing hip surgery. RESULTS: We
      found that Plin2 down-regulation was sufficient to induce a 30% increase of
      myofiber cross-sectional area, independently of mTOR pathway. Alterations of
      lipid content and modulation of genes involved in lipid synthesis occurred in
      hypertrophic muscles. In particular, we showed a decrease of triglycerides,
      ceramides, and phosphatidylcoline:phosphatidylethanolamine ratio, a condition
      known to impact negatively on muscle function. Plin2 overexpression did not
      change fibre size; however, lipid composition was strongly affected in a way that
      is similar to that observed in human samples from old patients. CONCLUSIONS:
      Altogether these data indicate that Plin2 is a critical mediator for the control
      of muscle mass, likely, but maybe not exclusively, through its critical role in
      the regulation of intracellular lipid content and composition.

PMID- 30288962
TI  - Uterine Receptivity in Merriam's Kangaroo Rat (Dipodomys merriami).
AB  - The uterine surface undergoes significant remodeling, termed the "plasma membrane
      transformation," during pregnancy to allow for implantation of the blastocyst and
      formation of the placenta in viviparous amniote vertebrates. Unlike other species
      within the superorder Euarchontoglires, which have a hemochorial (highly
      invasive) placenta, kangaroo rats (Dipodomys spp.) exhibit a less invasive
      endotheliochorial placenta. We characterized the changes that occur to membrane
      molecules and the cellular ultrastructure of the uterine epithelium during early
      pregnancy in Merriam's kangaroo rat, Dipodomys merriami using electron microscopy
      and immunofluorescence microscopy. Epithelial cadherin (E-cadherin) is an
      adhesion protein that forms the adherens junction and is localized to the lateral
      plasma membrane of uterine epithelium during the nonreproductive state but
      localizes nonspecifically in the uterine epithelium immediately preceding
      implantation. Desmosomes are a type of cadherin that form junctional complexes
      along the lateral plasma membrane of epithelium. Dsg-2, a marker for desmosomes,
      is localized along the lateral plasma membrane in non-pregnant animals but
      redistributes to the apical region of the lateral plasma membrane during early
      pregnancy. The shift in desmosome and cadherin distribution before implantation
      suggests that there is a reduction in lateral adhesion between epithelial cells
      to allow for invasion by the blastocyst. Surprisingly, although Kangaroo rats
      form a less invasive placenta, these same changes occur during pregnancy in
      species with highly invasive placentation, such as the laboratory rat and human.
      These commonalities suggest that it is not through the retention of lateral
      adhesion that the blastocyst is prevented from further invasion in this rodent
      species. Anat Rec, 301:1928-1935, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30288964
TI  - Facing Multiple Barriers to Exercise: Does Stronger Efficacy Help Individuals
      with Arthritis?
AB  - BACKGROUND: Research about exercise adherence amongst adults with arthritis has
      been largely correlational, and theoretically based causal studies are needed. We
      used an experimental design to test the social cognitive theory premise that high
      self-efficacy helps to overcome challenging barriers to action. METHODS:
      Exercising individuals (N = 86; female = 78%; M age = 53; BMI = 27) with
      differential self-regulatory efficacy for managing salient, non-disease barriers
      were randomly assigned to many or few barrier conditions. Individuals responded
      about the strength of their anticipated persistence to continue exercise, and
      their self-regulatory efficacy to use exercise-enabling coping strategies.
      RESULTS: In the many barriers condition, higher barriers-efficacy individuals
      expressed (a) greater persistence (Cohen's d = 0.75 [-0.029, 1.79]) and (b) more
      confidence in their coping solutions (Cohen's d = 0.65 [-0.30, 1.60]) than lower
      barriers-efficacy counterparts. CONCLUSION: Experimental support was obtained for
      the theoretical premise that when facing the greatest barrier challenge,
      individuals highest in self-regulatory efficacy still view exercise as possible.
      Findings suggest that identifying lower efficacy exercisers with arthritis to
      tailor their exercise to increase self-regulatory efficacy might also improve
      their adherence.

PMID- 30288963
TI  - C@TiO2 /MoO3 Composite Nanofibers with 1T-Phase MoS2 Nanograin Dopant and
      Stabilized Interfaces as Anodes for Li- and Na-Ion Batteries.
AB  - Integrating layered nanostructured MoS2 with a structurally stable TiO2 backbone
      to construct reciprocal MoS2 /TiO2 -based nanocomposites is an effective
      strategy. C@TiO2 /MoO3 composite nanofibers doped with 1T-phase MoS2 nanograins
      were fabricated by partially sulfurizing MoOx /TiO2 precursors. By controlling a
      suitable preoxidation temperature before severe thermolysis of
      polyvinylpyrrolidone (PVP), the MoOx /TiO2 precursors formed a polymer-embedded
      array through coordination of the Mo source and pyrrolidyl groups of PVP.
      Sulfidation under water/solvent hydrothermal conditions led to partial formation
      of metallic 1T-phase MoS2 from the MoOx precursor with preoxidation at 200 
      degrees C. After carbonization, the TiO2 /MoO3 /MoS2 nanograins were encapsulated
      in a carbon backbone in a vertical pattern, providing both chemical contact for
      confined electron transport and sufficient space to adapt to volume changes. The
      obtained carbon-based platform not only has the advantages of an integral
      structure, but also exhibited ultrastable specific capacities of 540 and 251 mAh
      g-1 for Li-ion batteries and Na-ion batteries, respectively, after 100 cycles.

PMID- 30288965
TI  - Nonscanning large-area Raman imaging for ex vivo/in vivo skin cancer
      discrimination.
AB  - Imaging Raman spectroscopy can be used to identify cancerous tissue.
      Traditionally, a step-by-step scanning of the sample is applied to generate a
      Raman image, which, however, is too slow for routine examination of patients. By
      transferring the technique of integral field spectroscopy (IFS) from astronomy to
      Raman imaging, it becomes possible to record entire Raman images quickly within a
      single exposure, without the need for a tedious scanning procedure. An IFS-based
      Raman imaging setup is presented, which is capable of measuring skin ex vivo or
      in vivo. It is demonstrated how Raman images of healthy and cancerous skin
      biopsies were recorded and analyzed.

PMID- 30288967
TI  - Providing Smartphones, Tablets and Other Devices to Employees to Facilitate
      Information Flow.

PMID- 30288968
TI  - Recommending the Flu Vaccine for the 2016-2017 Season: What You Should Know.

PMID- 30288969
TI  - Online Learning Modules Helping to Manage Physician Burnout.

PMID- 30288966
TI  - Strain-specific metastatic phenotypes in pheochromocytoma allograft mice
AB  - Somatostatin receptor-targeting endoradiotherapy offers potential for treating
      metastatic pheochromocytomas and paragangliomas, an approach likely to benefit
      from combination radiosensitization therapy. To provide reliable preclinical in
      vivo models of metastatic disease, this study characterized the metastatic spread
      of luciferase-expressing mouse pheochromocytoma (MPC) cells in mouse strains with
      different immunologic conditions. Bioluminescence imaging showed that, in
      contrast to subcutaneous non-metastatic engraftment of luciferase-expressing MPC
      cells in NMRI-nude mice, intravenous cell injection provided only suboptimal
      metastatic spread in both NMRI-nude mice and hairless SCID (SHO) mice. Treatment
      of NMRI-nude mice with anti-Asialo GM1 serum enhanced metastatic spread due to
      substantial depletion of natural killer (NK) cells. However, reproducible
      metastatic spread was only observed in NK cell-defective SCID/beige mice and in
      hairless immunocompetent SKH1 mice bearing disseminated or liver metastases,
      respectively. Liquid chromatography tandem mass spectrometry of urine samples
      showed that subcutaneous and metastasized tumor models exhibit comparable renal
      monoamine excretion profiles characterized by increasing urinary dopamine, 3
      methoxytyramine, norepinephrine and normetanephrine. Metastases-related
      epinephrine and metanephrine were only detectable in SCID/beige mice. Positron
      emission tomography and immunohistochemistry revealed that all metastases
      maintained somatostatin receptor-specific radiotracer uptake and
      immunoreactivity, respectively. In conclusion, we demonstrate that intravenous
      injection of luciferase-expressing MPC cells into SCID/beige and SKH1 mice
      provides reproducible and clinically relevant spread of catecholamine-producing
      and somatostatin receptor-positive metastases. These standardized preclinical
      models allow for precise monitoring of disease progression and should facilitate
      further investigations on theranostic approaches against metastatic
      pheochromocytomas and paragangliomas.

PMID- 30288971
TI  - Solid-State NMR Investigations of Carbon Dioxide Gas in Metal-Organic Frameworks:
      Insights into Molecular Motion and Adsorptive Behavior.
AB  - Solid-state nuclear magnetic resonance (SSNMR) methods have been routinely used
      for the characterization of both the structure and the dynamics of metal organic
      frameworks (MOFs), a collection of porous media investigated for potential
      applications in carbon capture technologies, selective separation of small
      molecules, and catalysis. (1) The use and development of SSNMR techniques that
      enable the nondestructive characterization of the adsorbed behavior have become
      essential steps in bettering our understanding of MOFs and are often
      complementary to traditional methods of structural characterization. This Review
      aims to give a brief introduction to the relevant concepts of SSNMR and the
      methods employed when investigating the phenomenon of adsorbed carbon dioxide gas
      in MOFs. We summarize the published SSNMR literature on CO2 in MOFs, as well as
      highlight the best experimental practices when working with these complex
      systems.

PMID- 30288970
TI  - Join Conversation: Caring for the Caregiver.

PMID- 30288972
TI  - Color-Tunable Phosphor [Mg1.25Si1.25Al2.5]O3N3:Eu2+-A New Modified Polymorph of
      AlON with Double Sites Related Luminescence and Low Thermal Quenching.
AB  - Aluminum oxynitride (AlON) was commonly used in functional ceramic materials,
      including phosphors for white light-emitting diodes (LEDs). In the current work,
      a new polymorph of AlON structure, single phase [Mg1.25Si1.25Al2.5]O3N3, has been
      devised and synthesized through the solid-state reaction at a rather low
      temperature of 1550  degrees C. Its structure has been calculated by the Rietveld
      refinement. The [Mg1.25Si1.25Al2.5]O3N3 crystallizes in trigonal with lattice
      parameters of a = b = 3.0312 A, c = 41.5758 A, V = 330.83 A3, respectively, and
      it is formed by Mg2+ and Si4+ ions replacing partical Al3+ ions of Al5O3N3. The
      photoluminescence spectra of a series of Eu2+ doped [Mg1.25Si1.25Al2.5]O3N3 show
      a tunable light ranging from cyan to orange with a full-spectrum-covered emission
      and a wide excitation band with two peaks located at 290 and 335 nm. This is
      resulted from the two possible sites offered by the cation substitution for Eu2+
      to occupy and thus broadening the emission spectra, which significantly enrich
      the monotonous luminescent properties of conventional AlON phosphors.
      Additionally, the energy transfer from one site to another has been identified
      using the decay curves and time-resolved emission spectra. The scanning electron
      microscopy and transmission electron microscopy characterization confirmed the
      sample's great crystallinity and the thermal stability with more than 85% of the
      initial intensity at 250  degrees C further indicates its potential in white LED
      applications.

PMID- 30288973
TI  - High-Throughput Open-Air Plasma Activation of Metal-Oxide Thin Films with Low
      Thermal Budget.
AB  - Sputter-processed oxide films are typically annealed at high temperature
      (activation process) to achieve stable electrical characteristics through the
      formation of strong metal-oxide chemical bonds. For instance, indium-gallium-zinc
      oxide (IGZO) films typically need a thermal treatment at 300  degrees C for >=1 h
      as an activation process. We propose an open-air plasma treatment (OPT) to
      rapidly and effectively activate sputter-processed IGZO films. The OPT
      effectively induces metal-oxide chemical bonds in IGZO films at temperatures as
      low as 240  degrees C, with a dwell time on the order of a second. Furthermore,
      by controlling the plasma-processing conditions (scan speed, distance a between
      plasma nozzle and samples, and gas flow rate), the electrical characteristics and
      the microstructure of the IGZO films can be easily tuned. Finally, OPT can be
      utilized to implement a selective activation process. Plasma-treated IGZO thin
      film transistors (TFTs) exhibit comparable electrical characteristics to those of
      conventionally thermal treated IGZO TFTs. Through in-depth optical, chemical, and
      physical characterizations, we confirm that OPT simultaneously dissociates weak
      chemical bonds by UV radiation and ion bombardment and re-establishes the metal
      oxide network by radical reaction and OPT-induced heat.

PMID- 30288974
TI  - Mild Reduction of the Cancer Cell Surface as an Anti-invasion Treatment.
AB  - Cancer cell invasion is the main reason for high mortality in patients with
      malignant cancers. There has been little improvement in cancer prognosis because
      of a high rate of infiltration. Therefore, successful treatment requires
      inhibition of cancer cell invasion. Here, we suggest a new approach to inhibit
      cancer cell invasion through mild reduction of cell surface proteins to expose
      free thiols. Through mild reduction, the cancer cell surfaces present free active
      thiols at the membranes, enhancing cell adhesion to extracellular matrix and
      decreasing motility. Collectively, we suggest cell surface modification as a new
      therapeutic approach to treat invading malignant cancers.

PMID- 30288975
TI  - Designing Surface Chemistry of Silver Nanocrystals for Radio Frequency Circuit
      Applications.
AB  - We introduce solution-based, room temperature- and atmospheric pressure-processed
      silver nanocrystal (Ag NC)-based electrical circuits and interconnects for radio
      frequency (RF)/microwave frequency applications. We chemically designed the
      surface and interface states of Ag NC thin films to achieve high stability, dc
      and ac conductivity, and minimized RF loss through stepwise ligand exchange,
      shell coating, and surface cleaning. The chemical and structural properties of
      the circuits and interconnects affect the high-frequency electrical performance
      of Ag NC thin films, as confirmed by high-frequency electromagnetic field
      simulations. An all solution-based process is developed to build coplanar
      structures, in which Ag NC thin films are positioned at both sides of the
      substrates. In addition, we fabricated flexible transmission lines and broadband
      electrical circuits for resistors, interdigitated capacitors, spiral and omega
      shaped inductors, and patch antennas with maximum inductance and capacitance
      values of 3 nH and 2.5 pF at frequencies up to 20 GHz. We believe that our
      approach will lead to a cost-effective realization of RF circuits and devices in
      which sensing and wireless communication capabilities are combined for internet
      of-things applications.

PMID- 30288976
TI  - An Integrated Source Apportionment Methodology and Its Application over the
      Yangtze River Delta Region, China.
AB  - An integrated source apportionment methodology is developed by amalgamating the
      receptor-oriented model (ROM) and source-oriented numerical simulations (SOM)
      together to eliminate the weaknesses of individual SA methods. This approach
      attempts to apportion and dissect the PM2.5 sources in the Yangtze River Delta
      region during winter. First, three ROM models (CMB, PMF, ME2) are applied and
      compared for the preliminary SA results, with information from PM2.5 sampling and
      lab analysis during the winter seasons. The detailed source category contribution
      of SOM to PM2.5 is further simulated using the WRF-CAMx model. The two pieces of
      information from both ROM and SOM are then stitched together to give a
      comprehensive information on the PM2.5 sources over the region. With the
      integrated approach, the detailed contributing sources of the ambient PM2.5 at
      different receptors including rural and urban, coastal and in-land, northern and
      southern receptors are analyzed. The results are compared with previous data and
      shows good agreement. This integrative approach is more comprehensive and is able
      to produce a more profound and detailed understanding between the sources and
      receptors, compared with single models.

PMID- 30288977
TI  - Bioactive Penicipyrrodiether A, an Adduct of GKK1032 Analogue and Phenol A
      Derivative, from a Marine-Sourced Fungus Penicillium sp. ZZ380.
AB  - Penicipyrrodiether A, an adduct of GKK1032 analogue and phenol A derivative, was
      isolated from a culture of marine-associated fungus Penicillium sp. ZZ380 and
      represents the first example of this type of fungal metabolite. Its structure was
      elucidated by extensive spectroscopic analyses, including 1D- and 2D-NMR,
      HRESIMS, MS/MS, and electronic circular dichroism calculation as well as single
      crystal X-ray diffraction. Penicipyrrodiether A showed antibacterial activity in
      inhibiting the growth of methicillin-resistant Staphylococcus aureus with a MIC
      value of 5.0 MUg/mL. Its plausible pathway for biosynthesis has been proposed.

PMID- 30288978
TI  - Dual-Stimuli Responsive Bismuth Nanoraspberries for Multimodal Imaging and
      Combined Cancer Therapy.
AB  - Development of stimuli-responsive theranostics is of great importance for precise
      cancer diagnosis and treatment. Herein, bovine serum albumin (BSA) modified
      bismuth nanoraspberries (Bi-BSA NRs) are developed as cancer theranostic agents
      for multimodal imaging and chemo-photothermal combination therapy. The Bi-BSA NRs
      are synthesized in aqueous phase via a facile reduction method using Bi2O3
      nanospheres as the sacrificial template. The morphology, biocompatibility,
      photothermal effect, drug loading/releasing abilities, chemotherapy effect,
      synergistic chemo-photothermal therapy efficacy, and multimodal imaging
      capacities of Bi-BSA NRs have been investigated. The results show that the NRs
      possess multiple unique features including (i) raspberry-like morphology with
      high specific surface area (~52.24 m2.g-1) and large cavity (total pore volume
      ~0.30 cm3.g-1), promising high drug loading capacity (~69 wt %); (ii) dual
      stimuli responsive drug release, triggered by acidic pH and NIR laser
      irradiation; (iii) infrared thermal (IRT), photoacoustic (PA) and X-ray computed
      tomography (CT) trimodality imaging with the CT contrast enhanced efficiency as
      high as ~66.7 HU.mL.mg-1; (iv) 100% tumor elimination through the combination
      chemo-photothermal therapy. Our work highlights the great potentials of Bi-BSA
      NRs as a versatile theranostics for multimodal imaging and combination therapy.

PMID- 30288979
TI  - Probing the Delicate Balance between Pauli Repulsion and London Dispersion with
      Triphenylmethyl Derivatives.
AB  - The long-known, ubiquitously present, and always attractive London dispersion
      (LD) interaction was probed with hexaphenylethane (HPE) derivatives. A series of
      all- meta hydrocarbyl [Me, iPr, tBu, Cy, Ph, 1-adamantyl (Ad)]-substituted
      triphenylmethyl (TPM) derivatives [TPM-H, TPM-OH, (TPM-O)2, TPM*] was synthesized
      en route, and several derivatives were characterized by single-crystal X-ray
      diffraction (SC-XRD). Multiple dimeric head-to-head SC-XRD structures feature an
      excellent geometric fit between the meta-substituents; this is particularly true
      for the sterically most demanding tBu and Ad substituents. NMR spectra of the iPr
      , tBu-, and Cy-derived trityl radicals were obtained and reveal, together with
      EPR and UV-Vis spectroscopic data, that the effects of all- meta alkyl
      substitution on the electronic properties of the trityl scaffold are marginal.
      Therefore, we concluded that the most important factor for HPE stability arises
      from LD interactions. Beyond all- meta tBu-HPE we also identified the hitherto
      unreported all- meta Ad-HPE. An intricate mathematical analysis of the
      temperature-dependent dissociation constants allowed us to extract Delta
      Gd298(exptl) = 0.3(5) kcal mol-1 from NMR experiments for all- meta tBu-HPE, in
      good agreement with previous experimental values and B3LYP-D3(BJ)/def2-TZVPP(C
      PCM) computations. These computations show a stabilizing trend with substituent
      size in line with all- meta Ad-HPE (Delta Gd298(exptl) = 2.1(6) kcal mol-1) being
      more stable than its tBu congener. That is, large, rigid, and symmetric
      hydrocarbon moieties act as excellent dispersion energy donors. Provided a good
      geometric fit, they are able to stabilize labile molecules such as HPE via strong
      intramolecular LD interactions, even in solution.

PMID- 30288980
TI  - Photoluminescent Phosphinine Cu(I) Halide Complexes: Temperature Dependence of
      the Photophysical Properties and Applications as a Molecular Thermometer.
AB  - Luminescent thermometers have attracted much attention, because of their fast
      response, high sensitivity, and noninvasive operation, relative to other
      traditional thermometers. The extensive studies on the temperature-dependent
      luminescent properties of Cu(I) complexes make this low-cost metal source a
      promising candidate as a component of thermometers. Herein, we prepared three
      luminescent phosphinine Cu(I) complexes whose emission lifetimes are precisely
      dependent on the temperature variations. For practical utilization, sensor films
      have been fabricated by doping these Cu(I) complexes into the matrices of
      polyacrylamide. These films not only exhibit excellent linear correlations
      between the temperature and emission lifetime over the wide range of 77-337 K,
      but also show high sensitivity (with the best one to -6.99 MUs K-1). These are
      essential factors for the application in luminescent molecular thermometers.
      Moreover, the emission mechanism for these Cu(I) complexes are rationalized by
      the combination of experimental and theoretical results.

PMID- 30288981
TI  - Sequential X-ray-Induced Single-Crystal to Single-Crystal Transformation followed
      by Topotactic Reduction in a Potassium Crown Ether Complex of
      Tetrachloroaurate(III).
AB  - During data collection, the unreported potassium crown ether salt [K(18-crown
      6][AuCl4] undergoes a sequential X-ray-induced and irreversible single-crystal to
      single-crystal transformation from P1 to C2/ c followed by a topotactic reduction
      to crystalline [K(18-crown-6][AuCl2] within the same C2/ c space group.

PMID- 30288982
TI  - Anomalous Exciton Quenching in Organic Semiconductors in the Low-Yield Limit.
AB  - The dynamics of exciton quenching are critical to the operational performance of
      organic optoelectronic devices, but their measurement and elucidation remain
      ongoing challenges. Here, we present a method for quantifying small
      photoluminescence quenching efficiencies of organic semiconductors under steady
      state conditions. Exciton quenching efficiencies of three different organic
      semiconductors, PC70BM, P3HT, and PCDTBT, are measured at different bulk quencher
      densities under continuous low-irradiance illumination. By implementing a steady
      state bulk-quenching model, we determine exciton diffusion lengths for the
      studied materials. At low quencher densities we find that a secondary quenching
      mechanism is in effect, which is responsible for approximately 20% of the total
      quenched excitons. This quenching mechanism is observed in all three studied
      materials and exhibits quenching volumes on the order of several thousand cubic
      nanometers. The exact origin of this quenching process is not clear, but it may
      be indicative of delocalized excitons being quenched prior to thermalization.

PMID- 30288983
TI  - Direct in Situ Observation and Analysis of the Formation of Palladium
      Nanocrystals with High-Index Facets.
AB  - Synthesizing concave-structured nanoparticles (NP) with high-index surfaces
      offers a viable method to significantly enhance the catalytic activity of NPs.
      Current approaches for fabricating concave NPs, however, are limited. Exploring
      novel synthesis methods requires a thorough understanding of the competing
      mechanisms that contribute to the evolution of surface structures during NP
      growth. Here, by tracking the evolution of Pd nanocubes into concave NPs at
      atomic scale using in situ liquid cell transmission electron microscopy, our
      study reveals that concave-structured Pd NPs can be formed by the cointroduction
      of surface capping agents and halogen ions. These two chemicals jointly create a
      new surface energy landscape of Pd NPs, leading to the morphological
      transformation. In particular, Pd atoms dissociate from the {100} surfaces with
      the aid of Cl- ions and preferentially redeposit to the corners and edges of the
      nanocubes when the capping agent polyvinylpyrrolidone is introduced, resulting in
      the formation of concave Pd nanocubes with distinctive high-index facets. Our
      work not only demonstrates a potential route for synthesizing NPs with well
      defined high-index facets but also reveals the detailed atomic-scale kinetics
      during their formation, providing insight for future predictive synthesis.

PMID- 30288984
TI  - Exploring the neurocognitive correlates of challenging behaviours in young people
      with autism spectrum disorder.
AB  - Many young people with autism spectrum disorder display 'challenging behaviours',
      characterised by externalising behaviour and self-injurious behaviours. These
      behaviours can have a negative impact on a young person's well-being, family
      environment and educational achievement. However, the development of effective
      interventions requires greater knowledge of autism spectrum disorder-specific
      models of challenging behaviours. Autism spectrum disorder populations are found
      to demonstrate impairments in different cognitive domains, namely social domains,
      such as theory of mind and emotion recognition, but also non-social domains such
      as executive functioning and sensory or perceptual processing. Parent-rated self
      injurious behaviour and externalising behaviours, and neurocognitive performance
      were assessed in a population-derived sample of 100 adolescents with autism
      spectrum disorder. Structural equation modelling was used to estimate
      associations between cognitive domains (theory of mind, emotion recognition,
      executive functioning and perceptual processing) and self-injurious behaviour and
      externalising behaviours. Poorer theory of mind was associated with increased
      self-injurious behaviour, whereas poorer perceptual processing was associated
      with increased externalising behaviours. These associations remained when
      controlling for language ability. This is the first analysis to examine how a
      wide range of neurocognitive domains relate to challenging behaviours and
      suggests specific domains that may be important targets in the development of
      interventions in adolescents with autism spectrum disorder.

PMID- 30288986
TI  - Technology in Public Health Higher Education.
AB  - Streamed and recorded lectures as well as audience response technology are
      increasingly used in public health tertiary education, to train practitioners to
      address Asia-Pacific region's rapidly changing health needs. However, little is
      known about the impact on student performance, satisfaction, and understanding.
      This study aimed to assess postgraduate students' perceptions and their use of
      technology in a large epidemiology subject at an Australian university in
      internal and external modes. The study used both routinely collected student data
      (n = 453) and survey data (n = 88). Results indicate that students accept and use
      technology-based learning tools, and perceive audience response technology as
      well as streamed and recorded lectures as useful for their learning (96.6%).
      Students have shown a preference to review recorded lectures rather than viewing
      streamed lectures. Analyses further suggest that the use of recorded and streamed
      lectures may be linked to better student performance for external students
      (passing, any use odds ratio = 3.32). However, these effects are not consistent
      across all student subgroups and externally enrolled students may profit more
      than those enrolled internally.

PMID- 30288985
TI  - Measurement Equivalence and Convergent Validity of a Mental Health Rating Scale.
AB  - Emotional and behavioral problems among children and adolescents may be studied
      using the Strengths and Difficulties Questionnaire, containing five subscales,
      based on ratings by parents, teachers, or adolescents themselves. We investigate
      two measurement issues using data from a longitudinal sample of 8,806
      participants aged 7 to 9 years and 11 to 13 years from the Bergen Child Study in
      Bergen, Norway. First, convergent validity of parent and teacher ratings is
      studied using a multitrait-multimethod approach. Second, longitudinal measurement
      equivalence is studied using confirmatory factor analysis, which requires us to
      deal with the considerable attrition. The multitrait-multimethod indicates not
      only good convergent validity but also considerable method variance for parents
      and teachers. The reliability and validity of some subscales are relatively low.
      Attrition analysis indicates that attrition is not missing completely at random,
      but estimation assuming missing at random makes no real difference. We conclude
      that assuming missing completely at random is acceptable. Comparing ratings by
      parents and teachers results in partial scalar equivalence. In addition, all
      subscales exhibit (partial) longitudinal scalar measurement equivalence. We
      recommend using latent variable modeling and not summated scales for longitudinal
      modeling using the Strengths and Difficulties Questionnaire.

PMID- 30288987
TI  - The Clindamycin Catastrophe: A Case of Antibiotic-Induced Skin Eruption.

PMID- 30288988
TI  - Exploring and building autism service capacity in rural and remote regions:
      Participatory action research in rural Alberta and British Columbia, Canada.
AB  - Based in participatory action research, this project had the aim of building
      capacity in treatment and support for individuals and families impacted by autism
      spectrum disorder in remote and rural communities of Canada. Communities were
      selected based on their rurality and willingness to engage in change efforts for
      enhanced service delivery within their region. Fifteen discussion groups with key
      stakeholders were convened in seven communities with ~200 community stakeholders.
      Based on analyses of these data from the stakeholders, themes were distilled
      through interpretive description, which in turn were presented to community
      stakeholders for reflection and collective action. Findings indicate broad
      thematic domains consisting of: insufficient services, protective factors in
      community, change efforts via collectivity within community, limitations and
      benefits of residing in rural communities relative to care associated with autism
      spectrum disorder, a sense of "community" in rural contexts, and engaging in
      focused dialogue as a pathway to advancement. Opportunities for building capacity
      for support in autism spectrum disorder emerged within intersecting layers of
      leadership, contextual factors, and community collaboration. Consistent with
      participatory action research principles, emerging local knowledge was supported
      with strategies for improved autism spectrum disorder service development.

PMID- 30288989
TI  - Adults with autism spectrum condition have atypical perception of ambiguous
      figures when bottom-up and top-down interactions are incongruous.
AB  - We examined the perception of an ambiguous squares stimulus evoking bistable
      perception in a sample of 31 individuals with autistic spectrum condition and 22
      matched typical adults. The perception of the ambiguous figure was manipulated by
      adaptation to unambiguous figures and/or by placing the ambiguous figure into a
      context of unambiguous figures. This resulted in four conditions testing the
      independent and combined (congruent and incongruent) manipulations of adaptation
      (bottom-up) and spatial context (top-down) effects. The strength of perception,
      as measured by perception of the first reported orientation of the ambiguous
      stimulus, was affected comparably between groups. Nevertheless, the strength of
      perception, as measured by perceptual durations, was affected differently between
      groups: the perceptual effect was strongest for the autistic spectrum condition
      group when combined bottom-up and top-down conditions were congruent. In
      contrast, the strength of the perceptual effect in response to the same condition
      in the typical adults group was comparable to the adaptation, but stronger than
      both the context and the incongruent combined bottom-up and top-down conditions.
      Furthermore, the context condition was stronger than the incongruent combined
      bottom-up and top-down conditions for the typical adults group. Thus, our
      findings support the view of stimulus-specific top-down modulation in autistic
      spectrum condition.

PMID- 30288990
TI  - U.S. News and World Report Top-Ranked Children's Hospitals and Academic
      Productivity.

PMID- 30288992
TI  - The Continued Impact of Marijuana Legalization on Unintentional Pediatric
      Exposures in Colorado.

PMID- 30288991
TI  - Quadriceps Function and Patient-Reported Outcomes After Anterior Cruciate
      Ligament Reconstruction in Patients With or Without Knee Osteoarthritis.
AB  - CONTEXT: Relationships between quadriceps function and patient-reported outcomes
      after anterior cruciate ligament reconstruction (ACLR) are variable and may be
      confounded by including patients at widely different time points after surgery.
      Understanding these relationships during the clinically relevant phases of
      recovery may improve our knowledge of specific factors that influence clinical
      outcomes. OBJECTIVE: To identify the relationships between quadriceps function
      and patient-reported outcomes in patients <2 years (early) and >2 years (late)
      after ACLR, including those with posttraumatic knee osteoarthritis. DESIGN: Cross
      sectional study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of
      72 patients after ACLR: early (n = 34, time from surgery = 9.0 +/- 4.3 months),
      late (n = 30, time from surgery = 70.5 +/- 41.6 months), or osteoarthritis (n =
      8, time from surgery = 115.9 +/- 110.0 months). MAIN OUTCOME MEASURE(S): The
      total Knee Injury and Osteoarthritis Outcome Score (KOOS) and Veterans RAND 12
      Item Health Survey (VR-12) were used to quantify knee function and global health.
      Predictors of patient-reported outcomes were involved-limb and symmetry indices
      of quadriceps function (isokinetic strength [peak torque, total work, average
      power], maximum voluntary isometric contraction torque, fatigue index, central
      activation ratio, Hoffmann reflex, active motor threshold) and demographics (age,
      activity level, pain, kinesiophobia, time since surgery). Multiple linear
      regression analyses were used to predict KOOS and VR-12 scores in each group.
      RESULTS: In the early patients, knee-extensor work, active motor threshold
      symmetry, pain, and activity level explained 67.8% of the variance in the KOOS
      score ( P < .001); knee-extensor work, activity level, and pain explained 53.0%
      of the variance in the VR-12 score ( P < .001). In the late patients, age and
      isokinetic torque symmetry explained 28.9% of the variance in the KOOS score ( P
      = .004). In the osteoarthritis patients, kinesiophobia and isokinetic torque
      explained 77.8% of the variance in the KOOS score ( P = .010); activity level
      explained 86.4% of the variance in the VR-12 score ( P = .001). CONCLUSIONS:
      Factors of muscle function and demographics that explain patient-reported
      outcomes were different in patients early and late after ACLR and in those with
      knee osteoarthritis.

PMID- 30288993
TI  - Breast Abscess Sequelae.

PMID- 30288994
TI  - Micronutrient Intake and Risk of Hematological Malignancies in Adults: A
      Systematic Review and Meta-analysis of Cohort Studies.
AB  - There has been accumulating evidence that several micronutrients may play a
      protective role in the risk of solid cancers. However, their role in
      hematological malignancies remains to be elucidated; this meta-analysis aims to
      evaluate the associations between micronutrient intake as well as supplementation
      and risk of hematological cancer in adults. Eligible cohort studies (examining
      intake of vitamin A, vitamin C, vitamin D, vitamin E, lycopene, folate, iron,
      carotenoids, beta-carotene, selenium, pyridoxine) were sought in PubMed up to
      July 31, 2016. Random-effects models were used for the calculation of pooled
      relative risks (RR) with their 95% confidence intervals (CI). Twelve cohort
      studies were deemed eligible. Null associations were noted regarding supplemented
      vitamin A (pooled relative risk [RR] = 0.92, 95% confidence interval [CI]: 0.80
      1.07), supplemented vitamin C (pooled RR = 1.00, 95%CI: 0.90-1.12), total vitamin
      D (pooled RR = 1.05, 95%CI: 0.91-1.20), supplemented vitamin E (pooled RR = 0.98,
      95%CI: 0.88-1.10), and dietary lycopene intake (pooled RR = 1.00, 95%CI: 0.86
      1.16) and the risk of non-Hodgkin lymphoma. No summary estimates are provided for
      other hematological malignancies due to the limited number of studies. Future
      prospective trials should be conducted for a better understanding of this field;
      especially regarding Hodgkin lymphoma, leukemia and plasma cell neoplasms, on
      which data are scarce.

PMID- 30288995
TI  - Betulinic acid improves insulin sensitivity, hyperglycemia, inflammation and
      oxidative stress in metabolic syndrome rats via PI3K/Akt pathways.
AB  - This study investigated the influence of betulinic acid on high-fructose diet
      induced metabolic syndrome in rats. Oral administration of betulinic acid
      significantly reversed high-fructose diet-mediated increase in body mass index
      and blood glucose. Furthermore, betulinic acid restored high-fructose diet
      mediated alterations in metabolic hormones (insulin, leptin and adiponectin).
      Betulinic acid-mediated upregulation of protein kinase B (Akt) and
      phosphoinositde-3 kinase (PI3K) anulled high-fructose diet mediated depletion.
      Also, elevated tumour necrosis factor-alpha, interleukin-6 and -8 were
      significantly lowered. Administration of betulinic acid restored high-fructose
      diet-mediated increase in the levels of lipid profile parameters and indices of
      atherosclerosis, cardiac and cardiovascular diseases. High-fructose diet-mediated
      decrease in activities of antioxidant enzymes (superoxide dismutase, catalase,
      glutathione peroxidase, glutathione reductase and glucose 6-phosphate
      dehydrogenase) and increase in oxidative stress biomarkers (reduced glutathione,
      lipid peroxidation products, protein oxidation and fragmented DNA) were
      significantly restored by the phenolic acids. Conclusively, betulinic acid
      improves insulin sensitivity, elevated blood glucose, inflammation and
      dyslipidaemia and oxidative stress in high-fructose diet-induced metabolic
      syndrome through the PI#Kand Akt pathways .

PMID- 30288996
TI  - Inhibition of Nf-?b prevents trauma-induced heterotopic ossification in rat
      model.
AB  - PURPOSE: To investigate the pathogenesis and find a better prophylactic method of
      acquired heterotopic ossification (HO). MATERIALS AND METHODS: In the first part,
      we designed the brain-traumatic/burn/tenotomy rat model and testified its
      efficacy as HO model. 44 rats were randomly divided into experimental group and
      control group. After operation, the bilateral tendons of 2 rats were collected at
      the 2nd, 3rd, 4th, 6th, 8th, and 10th weeks to determine the expression levels of
      p65. Additionally, the remaining rats were exposed to X-Ray examination at the
      10th week. In the second part, 124 rats were randomly divided into four groups
      based on the administration dosage of Ammonium pyrrolidinedithiocarbamate (PDTC).
      Then, three rats of each group were euthanized every week in the first seven
      weeks to collect tendon to detect the expression levels of p65 by qRT-PCR and
      Western Blot. The remaining rats were exposed to X-Ray examination at the 10th
      week to assess the size of HO before being euthanized for HE staining. RESULTS:
      The success rate of Brain-traumatic/Burn/Tenotomy model was 100%. Pharmacologic
      inhibition of Nf-?b signaling pathway by PDTC could significantly reduce the
      expression levels of p53 and the size of HO, and the reduction was most
      significant in the 0.6mg dosage group. CONCLUSIONS: Brain-traumatic/Burn/Tenotomy
      model was highly reliable HO model. Inhibition of Nf-?b signaling pathway by PDTC
      could significantly reduce HO formation, and the most effective concentration was
      6 mg/ml for local injection.

PMID- 30288997
TI  - Deep learning and virtual drug screening.
AB  - Current drug development is still costly and slow given tremendous technological
      advancements in drug discovery and medicinal chemistry. Using machine learning
      (ML) to virtually screen compound libraries promises to fix this for generating
      drug leads more efficiently and accurately. Herein, we explain the broad basics
      and integration of both virtual screening (VS) and ML. We then discuss artificial
      neural networks (ANNs) and their usage for VS. The ANN is emerging as the
      dominant classifier for ML in general, and has proven its utility for both
      structure-based and ligand-based VS. Techniques such as dropout, multitask
      learning and convolution improve the performance of ANNs and enable them to take
      on chemical meaning when learning about the drug-target-binding activity of
      compounds.

PMID- 30288998
TI  - Chemokine and Adhesion Molecule Profiles in Aqueous Humor of Clinically Quiescent
      Uveitic Cataracts.
AB  - PURPOSE: To investigate the chemokine and adhesion molecule profiles in aqueous
      humor (AH) of eyes with inactive uveitis and their correlations with inflammation
      relapse after cataract surgery. METHODS: Patients with inactive uveitis who
      underwent cataract surgery between July 2014 and January 2016 at our center were
      included. Undiluted AH samples (100-120 ul) were obtained through lateral corneal
      incisions during surgery, and concentrations of monocyte chemoattractant protein
      1 (MCP-1/CCL2), macrophage inflammatory protein 1 (MIP-1), interleukin 8 (IL-8),
      regulated on activation, normal T cell expressed and secreted (RANTES/CCL5),
      soluble vascular cell adhesion molecule (sVCAM) and soluble intercellular
      adhesion molecule (sICAM) were measured by cytometric bead array (BD Bioscience,
      San Jose, CA). AH levels of these inflammatory factors were compared between
      different uveitis entities and non-inflammatory control. Risk factors for
      postoperative inflammation relapse were also analysed in uveitic eyes. RESULTS:
      As compared with the control group, the panuveitis group had significantly higher
      aqueous concentrations of MCP-1, IL-8, sVCAM, sICAM; the anterior uveitis group
      had significantly higher concentrations of MCP-1, MIP-1, sVCAM. Uveitic cataracts
      with postoperative inflammation relapse had significantly higher levels of MCP-1
      and IL-8 in AH than those without. And multivariate cox regression analysis
      revealed that high AH levels of MCP-1 was an independent predictor for
      postoperative inflammation relapse. CONCLUSIONS: Clinically quiescent uveitic
      eyes have elevated levels of chemokines and soluble adhesion molecules in AH, of
      which MCP-1 is associate with inflammation relapses after cataract surgery.

PMID- 30288999
TI  - Women's Experiences of Day-and-Night Closed-Loop Insulin Delivery During Type 1
      Diabetes Pregnancy.
AB  - AIMS:: Closed-loop insulin delivery has the potential to improve day-to-day
      glucose control in type 1 diabetes pregnancy. However, the psychosocial impact of
      day-and-night usage of automated closed-loop systems during pregnancy is unknown.
      Our aim was to explore women's experiences and relationships between technology
      experience and levels of trust in closed-loop therapy. METHODS:: We recruited 16
      pregnant women with type 1 diabetes to a randomized crossover trial of sensor
      augmented pump therapy compared to automated closed-loop therapy. We conducted
      semistructured qualitative interviews at baseline and follow-up. Findings from
      follow-up interviews are reported here. RESULTS:: Women described benefits and
      burdens of closed-loop systems during pregnancy. Feelings of improved glucose
      control, excitement and peace of mind were counterbalanced by concerns about
      technical glitches, CGM inaccuracy, and the burden of maintenance requirements.
      Women expressed varied but mostly high levels of trust in closed-loop therapy.
      CONCLUSIONS:: Women displayed complex psychosocial responses to day-and-night
      closed-loop therapy in pregnancy. Clinicians should consider closed-loop therapy
      not just in terms of its potential impact on biomedical outcomes but also in
      terms of its impact on users' lives.

PMID- 30289000
TI  - Antimicrobial pentacyclic triterpenes and glycosides from the stem bark of
      Cussonia bancoensis.
AB  - The stem bark of Cussonia bancoensis is used traditionally for the treatment of
      different types of infection and pain. A bioassay guided fractionation of the
      methanol stem bark extract led to the isolation of five pentacyclic triterpenes
      and glycosides identified based on spectroscopic data as 23-hydroxyursolic acid
      (CB1), hederagenin (CB2), 3-O-alpha-L-arabinopyranosyl-echinocystic acid (CB3), 3
      O-alpha-L-arabinopyranosyl- oleanolic acid (CB4) and 3-O-alpha-L-arabinopyranosyl
      ursolic acid (CB5). CB2 - CB5 are being reported for the first time from this
      species. The compounds were evaluated for antimicrobial activity against ten
      microorganisms using the HT-SPOTi method. CB3 demonstrated remarkable
      antimicrobial activity against S. aureus, S. pyogens, E. faecalis, S. typhi and
      C. albicans at MICs between 3.12 and 12.5 ug/mL. Among the studied compounds, it
      was observed that hydroxylation of position C-16 of the oleanane skeleton may
      enhance antimicrobial activity. This study gives insight into the anti-infective
      constituents of the stem bark of C. bancoensis and justifies its use in
      ethnomedicine.

PMID- 30289002
TI  - Phylogeny and acoustic signal evolution of a pure tone song katydid Pseudophyllus
      titan (Orthoptera: Tettigoniidae) based on the complete mitogenome.
AB  - Ensifera is an extremely diverse group in the order Orthoptera, and it has been
      the subject of considerable research, especially in terms of phylogeny and
      bioacoustics. Katydids are known for using high-frequency broadband signals
      whereas most cricket songs are pure tones with a frequency range of 2-8 kHz.
      Pseudophyllus titan is a special katydid emits low-frequency pure tone songs
      similar to that of crickets. Acoustic communication of Ensifera were widely
      studied, but song evolution could deserve new examination taking into account the
      newly available phylogenies. To examine the song evolution of P. titan in the
      Ensifera, the mitogenomes of P. titan and three other ensiferan species
      (Sphagniana ussuriana, Oecanthus sinensis, Truljalia hibinonis) were obtained by
      high-throughput sequencing. In addition, the phylogeny of Ensifera was
      reconstructed including 63 in-group taxa, and the divergence time was further
      estimated for major ensiferan lineages. Lastly, the evolutions of song frequency
      were evaluated based on an ancestral character state reconstruction (ACSR).
      Moreover, we have studied the calling songs of 78 katydids and performed ACSR
      based on five genes. All phylogeny analyses confirmed that the superfamily
      Schizodactyloidea was placed basally to the non-grylloid clade. P. titan was in
      the Pseudophyllinae clade, and this clade had a distant relationship form other
      lineages in Phaneropteridae. The ACSR showed that P. titan evolved low-frequency
      pure tone songs independently after ancestors of katydids evolved high-frequency
      broadband noise. Referring to the geologic time scale, we suggest that the song
      frequency evolution in the Ensifera to some extent caused by adaptations to the
      changing habitat under conditions of climate change and plant evolution.

PMID- 30289001
TI  - Extended Sinus Tarsi Approach for Treatment of Displaced Intraarticular Calcaneal
      Fractures Compared to Extended Lateral Approach.
AB  - BACKGROUND: We compared the radiographic results and clinical outcomes of
      patients operated on via the extended sinus tarsi approach (ESTA) and the
      extended lateral approach (ELA) for treatment of displaced intraarticular
      calcaneal fractures. METHODS: We retrospectively studied the utility of the ELA
      (46 patients, 52 feet) and the ESTA (56 patients, 64 feet) in patients operated
      on between January 2009 and March 2015. We evaluated pre- and postoperative x
      rays and computed tomography (CT) data. Pain, patient-reported functional
      outcomes, satisfaction, and postoperative complications were investigated at the
      3-year follow-up. RESULTS: Neither the postoperative nor 3-year follow-up Bohler
      angles, nor the calcaneal width, differed significantly between the 2 groups
      (both P > .05). However, the maximum step-off of the posterior facet on the 3
      month CT follow-up of the ESTA group was significantly less than that of the ELA
      group ( P < .05). We found no significant between-group differences in terms of
      postoperative translation ( P = .232) or angulation ( P = .132) of the
      sustentacular fragment on the 3-month CT follow-up. At the 3-year follow-up, we
      found no significant between-group difference in the mean visual analog scale
      pain score at rest ( P = .641) or during weightbearing ( P = .525). We found no
      significant between-group difference in the Foot Function Index (FFI) ( P = .712)
      or self-reported satisfaction ( P = .823). The ELA group experienced
      significantly more wound complications ( P = .041) and nonunions ( P = .041) than
      the ESTA group. Four instances of superficial peroneal nerve injury were reported
      in the ESTA group ( P = .127). CONCLUSION: Compared with the ELA, the ESTA
      afforded comparable, favorable radiological results and clinical outcomes,
      associated with fewer wound complications and nonunions. We suggest that the ESTA
      is an effective operative option when treating displaced, intraarticular
      calcaneal fractures. LEVEL OF EVIDENCE: Level III, comparative study.

PMID- 30289003
TI  - Vitamin B12 buccoadhesive tablets: auspicious non-invasive substitute for intra
      muscular injection: formulation, in vitro and in vivo appraisal.
AB  - Attempting to prepare a convenient bioavailable formulation of vitamin B12
      (cyanocobalamin), 17 tablet formulations were prepared by direct compression.
      Different concentrations of hydroxypropyl methyl cellulose (HPMC), carbopol 971p
      (CP971p), and chitosan (Cs) were used. The tablets were characterized for
      thickness, weight, drug content, hardness, friability, surface pH, in vitro drug
      release, and mucoadhesion. Kinetic analysis of the release data was conducted.
      Vitamin B12 bioavailability from the optimized formulations was studied on
      rabbits by the aid of enzyme-linked immunosorbent assay. Neurotone(r) I.M.
      injection was used for comparison. HPMC (F1-F4), CP971p (F5-F8), and HPMC/CP971p
      (F12-F15)-based formulations showed acceptable mechanical properties. The
      formulated tablets showed maximum swelling indices of 232 +/- 0.13. The surface
      pH values ranged from 5.3 +/- 0.03 to 6.6 +/- 0.02. Bioadhesive force ranged from
      66 +/- 0.6 to 150 +/- 0.5 mN. Results showed that CP971p-based tablets had
      superior in vitro drug release, mechanical, and mucoadhesive properties. In vitro
      release date of selected formulations were fitted well to Peppas model.
      HPMC/CP971p-based formulations showed bioavailability up to 2.7-folds that of
      Neurotone(r) I.M. injection.

PMID- 30289004
TI  - Real-world treatment patterns of PCSK9 inhibitors among patients with
      dyslipidemia in Germany, Spain, and the United Kingdom.
AB  - OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 antibody inhibitors
      (PCSK9i) are approved as adjuncts to maximal tolerated statin therapy to lower
      low-density lipoprotein cholesterol (LDL-C). This study describes real-world use,
      characteristics of PCSK9i users and non-users, and factors influencing treatment
      choice. METHODS: A physician and patient survey was conducted in Germany, Spain,
      and the UK from December 2016 to April 2017 through the Adelphi Dyslipidemia
      Disease Specific Program. Physicians reported patients' lipid-lowering therapy
      (LLT) history and characteristics. PCSK9i users were systematically over-sampled.
      Results were summarized using frequencies and proportions. RESULTS: The study
      included 110, 123, and 117 physicians from Germany, Spain, and the UK,
      respectively, providing data on 3,073 patients (mean age = 62 years; 60% male).
      Most patients (63-73%) had prior statin and/or ezetimibe use. Compared to
      patients receiving other LLT (n = 2686), PCSK9i users (222 in Germany, 97 in
      Spain, 68 in the UK) were, on average, 5-7.5 years younger and had LDL-C at
      diagnosis averaging 23-53 mg/dl higher. Familial hypercholesterolemia (FH),
      coronary heart/artery disease, myocardial infarction, and acute coronary syndrome
      were more common among PCSK9i users than non-users. PCSK9i users were also more
      likely to use high-intensity statins in their current LLT regimen (64-89% vs 28
      50%). Physicians commonly reported PCSK9i benefits on LDL-C and total cholesterol
      as reasons for initiating these agents, and PCSK9i users reported good knowledge
      of cardiovascular disease and treatment options. CONCLUSIONS: Results indicate
      that physicians are prescribing PCSK9i to patients with high cardiovascular risk
      in accordance with European guidelines and reimbursement requirements.

PMID- 30289006
TI  - A Commercially Available Thermogenic Dietary Supplement Increases Resting
      Metabolic Rate in Physically Active Males: A Randomized, Double-Blind, Placebo
      Controlled Investigation.
AB  - Males seeking to improve body composition may ingest thermogenic dietary
      supplements with the goal of elevating resting metabolic rate. The purpose of
      this study was to examine the effects of a commercially available dietary
      supplement (containing ingredients that promote thermogenesis) on resting
      metabolic rate (RMR) in a randomized, double-blind, placebo-controlled cross-over
      study. Ten healthy, physically active males (age: 26.5 +/- 6.4 years; height:
      177.6 +/- 7.2 cm; body weight: 80.5 +/- 10.8 kg) underwent two testing sessions
      separated by approximately 7 days. Following baseline assessments of RMR, heart
      rate (HR), and blood pressure (BP), each participant ingested a thermogenic
      dietary supplement or a placebo. Assessments were repeated at 60, 120, and 180
      minutes postingestion. Approximately 1 week later, participants ingested the
      alternative supplement and the assessments were repeated. Post hoc analyses
      revealed that the dietary supplement treatment demonstrated significant
      elevations in RMR during the postingestion period (p < 0.05) from 1,859 +/- 266
      kcal to 2,027 +/- 288 kcal (increase of 9%) to 2,072 +/- 292 kcal (increase of
      11.5%) and to 2,040 +/- 271 kcal (increase of 9.7%) at 60, 120, and 180 minutes
      postingestion, respectfully. No significant elevations were observed in the
      placebo treatment at any time point. HR and BP measures were within normal
      clinical values throughout the intervention.

PMID- 30289005
TI  - Phase II Trial of Acai Juice Product in Biochemically Recurrent Prostate Cancer.
AB  - BACKGROUND: Plant derivatives have been studied as therapies for prostate cancer
      based on their purported anti-inflammatory and antioxidant properties and low
      toxicities. The acai berry is an example of a plant rich in phytochemicals, which
      may slow the growth of prostate cancer. METHODS: This was a phase II, Simon 2
      stage clinical trial in patients with biochemically recurrent prostate cancer
      with a primary endpoint of prostate-specific antigen (PSA) response. Patients
      were asymptomatic, with a rising PSA of at least 0.2 ng/mL, and were treated with
      twice daily intake of Acai Juice Product until PSA progression, with a primary
      endpoint of PSA response. RESULTS: Twenty-one patients were enrolled in the first
      stage of the trial. One of those patients had a PSA response within the study
      time period. The PSA doubling time was lengthened in 71% of patients (95%
      confidence interval = 48% to 89%) on the trial, and in a small number of
      responders, this was sustained over an extended time. CONCLUSIONS: This study did
      not meet its primary endpoint of 50% PSA response. Nevertheless, the overall
      tolerability and effects on PSA stabilization warrant further exploration in a
      biochemically recurrent population.

PMID- 30289007
TI  - Visceral leishmaniasis elimination targets in India, strategies for preventing
      resurgence.
AB  - INTRODUCTION: Visceral leishmaniasis (VL) is a fatal parasitic disease caused by
      a parasite belonging to the Leishmania donovani complex and transmitted by
      infected female Phlebotomous argentipes sand flies. The VL elimination strategy
      in the Indian subcontinent (ISC), which has a current goal of reducing the
      incidence of VL to below 1/10,000 of population by the year 2020, consists of
      rapid detection and treatment of VL to reduce the number of human reservoirs as
      well as vector control using indoor residual spraying (IRS). However, as the
      incidence of VL declines toward the elimination goal, greater targeting of
      control methods will be required to ensure appropriate early action to prevent
      the resurgence of VL. Area covered: We discuss the current progress and
      challenges in the VL elimination program and strategies to be employed to ensure
      sustained elimination of VL. Expert commentary: The VL elimination initiative has
      saved many human lives; however, for VL elimination to become a reality in a
      sustained way, an intense effort is needed, as substantial numbers of endemic
      subdistricts (primary health centers (PHCs) blocks level) are yet to reach the
      elimination target. In addition to effective epidemiological surveillance,
      appropriate diagnostic and treatment services for VL at PHCs will be needed to
      ensure long-term sustainability and prevent reemergence of VL.

PMID- 30289008
TI  - Calendula officinalis: Potential Roles in Cancer Treatment and Palliative Care.
AB  - A continuous challenge in cancer management is to improve treatment efficacy and
      to diminish its side effects. Consequently, new conventional and unconventional
      drugs and bioactive compounds from plants are constantly developed,
      characterized, and used for in vitro and in vivo models. This review focuses on
      the antitumor properties of Calendula officinalis, its biological and molecular
      effects in tumor cells and animal models, as well as its role in cancer
      palliative care. A systematic review of studies describing the cytotoxic role of
      C officinalis and its therapeutic role on cancer cells were carried out using the
      PubMed database. Albeit C officinalis extracts have cytotoxic activity toward
      different cancer cell lines, a high grade of variation between studies was
      observed, depending on plant organ subjected to extraction, extraction method,
      and the cancer cell lines used for each study. Nevertheless, its cytotoxic
      activity is related to a few bioactive compounds, presenting multiple roles in
      both activation of proapoptotic proteins and decreasing the expression of the
      proteins that inhibit cell death. Moreover, due to its anti-genotoxic/protective
      as well as antitumor and antimetastatic effects proven in animal models, C
      officinalis could have important future implications in developing novel cancer
      treatment strategies, while until now it has been used especially for diminishing
      the side effects of radiotherapy.

PMID- 30289009
TI  - The economic burden of uncontrolled gout: how controlling gout reduces cost.
AB  - AIM: To evaluate the burden of uncontrolled gout by examining estimated costs and
      cost drivers. MATERIALS AND METHODS: Data from the 2012 and 2013 US National
      Health and Wellness Survey (NHWS; 2012 NHWS, n = 71,157 and 2013 NHWS, n =
      75,000) were utilized in this study. Based on self-reported gout diagnosis and
      gout symptoms, respondents were categorized into three groups: controlled gout (n
      = 344), uncontrolled gout (n = 2,215), and non-gout controls (n = 126,360). Chi
      square tests and one-way analysis of variance (ANOVAs) were used to assess group
      differences on work productivity loss, healthcare resource utilization, and
      costs. Zero-inflated negative binomial regressions were used to assess the burden
      of uncontrolled gout on total costs after controlling for covariates. RESULTS:
      Patients with uncontrolled gout had higher presenteeism, overall work impairment,
      activity impairment, and number of emergency department visits than those with
      controlled gout or controls. Overall, uncontrolled gout patients had both higher
      indirect and total costs compared to patients with controlled gout. After
      controlling for confounders, those with uncontrolled gout had higher total costs
      than controlled gout respondents and non-gout controls; there was no significant
      difference in total costs between patients with controlled gout and non-gout
      controls. LIMITATIONS: Results were based on cross-sectional, self-reported data,
      making causal inferences more uncertain. Additionally, sample size was small for
      controlled-gout respondents. Lastly, sampling weights were not used, thus
      potentially limiting generalizability. CONCLUSION: Gout can be an expensive
      condition, particularly if it is not properly controlled. This study provides
      support that controlling symptoms (e.g. flares) can reduce the economic and
      societal burden of gout. Therefore, more attention needs to be paid to effective
      management of gout symptoms.

PMID- 30289010
TI  - Evaluating the cost-effectiveness of secukinumab in moderate-to-severe psoriasis:
      a Japanese perspective.
AB  - AIM: To evaluate the cost-effectiveness of secukinumab, a fully human anti
      interleukin-17A monoclonal antibody, compared to other clinically used biologics
      (adalimumab, infliximab, and ustekinumab) in Japan for the treatment of moderate
      to-severe psoriasis from the healthcare system (total costs) and patient co
      payment (using different frequencies of drug purchase) perspectives. METHODS: A
      decision-tree (first year)/Markov model (subsequent years), with an annual cycle,
      was developed. The model adopted a 5-year time horizon. Efficacy inputs were
      obtained from a mixed-treatment comparison analysis, and other model inputs were
      collected from published literature and local Japanese sources. Model outcomes
      included quality-adjusted life years (QALYs) and an incremental cost
      effectiveness ratio (ICER) in terms of cost per QALY gained. The annual
      discounting rate of 2% was applied to both costs and outcomes. RESULTS: Results
      for the healthcare system perspective showed that secukinumab had the highest
      number of quality-adjusted life years (QALYs) (4.07) vs other biologics,
      dominated ustekinumab and infliximab, and the ICER of secukinumab compared to
      adalimumab was Y8,418,222/QALY gained. In the patient co-payment perspective with
      the monthly purchase of drugs, ustekinumab had the lowest co-payment cost,
      followed by infliximab, adalimumab, and secukinumab. In the patient co-payment
      perspective with a once every 3 months purchase of secukinumab and adalimumab,
      the co-payment costs of secukinumab, adalimumab, and ustekinumab became
      comparable, and infliximab had the highest co-payment cost. LIMITATIONS: Only
      short-term efficacy data was modeled, as there was a lack of data on long-term
      outcomes. Treatment sequencing was restricted to first-line biologic treatment.
      Drop-out rates for comparators were assumed to be equivalent to secukinumab in
      the absence of available data. CONCLUSIONS: Secukinumab is a cost-efficient
      treatment for moderate-to-severe psoriasis, providing greater health outcomes to
      patients at lower total costs compared to infliximab and ustekinumab, as well as
      comparable patient co-payment relative to other biologic treatments.

PMID- 30289011
TI  - Quality Control Standardization and Evaluation of Antimicrobial Potential of
      Daruhaldi (Berberis aristata DC) Stem Bark.
AB  - Berberis aristata is used for the treatment of diabetes, piles, and liver
      diseases. As the drug is broadly used in Indigenous systems of medicine, it was
      designed to set the quality standards and antimicrobial potential for the stem
      bark of Berberis aristata. Botanical, physicochemical, pharmacotoxicological,
      fluorescence, microbial load, and phytochemical parameters of the stem bark were
      determined. High-performance thin-layer chromatography (HPTLC) was carried out by
      the CAMAG-HPTLC system. Berberine, total phenolics, and flavonoids were
      estimated. The antimicrobial potential was determined against the bacteria
      Bacillus subtilis and Escherichia coli and fungi Penicillium citrinum and
      Aspergillus terreus. The foreign matter, foaming index, swelling index,
      bitterness value, resin content, loss on drying, total ash, acid-insoluble ash,
      water-soluble ash, heavy metals, microbial load, berberine content, total
      phenolic content, and total flavonoid content were found to be 0, 0, 5, 1.34,
      0.86%, 2.07%, 4.33%, 0.28%, 2.66%, within limits, 6 colonies in 1/100 dilution,
      0.032 mg/g, 144.04 ug/ml, and 85.61 ug/ml, respectively. Phytochemicals such as
      phenolics, flavonoids, and sterols were present in the methanolic extract. The
      fluorescences observed in UV light were of different colors in different
      solvents. The methanolic extract and standards exhibited antimicrobial activity
      at the tested concentrations against the microbial strains. Results confirmed the
      quality and purity of the drug B. aristata. Results also confirmed that
      methanolic extract of B. aristata stem bark possesses potent antimicrobial
      activity. Thus, the use of this quality-controlled plant-derived drug with
      established antimicrobial property could be of great significance in quality
      control standardization and preventive and therapeutic approaches to infectious
      diseases.

PMID- 30289012
TI  - Genipin crosslinked curcumin loaded chitosan/montmorillonite K-10 (MMT)
      nanoparticles for controlled drug delivery applications.
AB  - Here, we have reported the influence of MMT and genipin in releasing curcumin
      from the Genipin crosslinked Chitosan/MMT nanoparticles, prepared by ionic
      gelation method. The nanoparticles were characterised using Fourier Transform
      Infrared Spectroscopy (FTIR), X-Ray Diffractometry (XRD), Scanning Electron
      Microscopy (SEM), and Transmission Electron Microscopy (TEM). Zeta potential and
      average diameter of the nanoparticles were found in the range 32-47 mV and 430
      560 nm. Swelling and release of curcumin from the nanoparticles increased with
      the decrease in pH of the medium, MMT, and genipin content. Curcumin released
      from the nanoparticles reduced the viability of MCF-7 and Hep G2 cells as
      compared to untreated cells. The nanoparticles increased the level of reduced
      glutathione (GSH), superoxide dismutase (SOD), and catalase level in human PBMCs
      and decreased the level of Lipid peroxidation suggesting an enhanced protection
      against cellular damage. Lower pH and higher MMT concentration in the
      nanoparticles improved the mucoadhesive properties.

PMID- 30289013
TI  - Clinicopathological characteristics and renal outcomes of childhood-onset lupus
      nephritis with acute kidney injury: a multicenter study.
AB  - OBJECTIVES: Acute kidney injury (AKI) at onset of adult systemic lupus
      erythematosus (SLE) is a risk factor for end stage kidney disease (ESKD).
      However, data on childhood-onset lupus nephritis (LN) with AKI are scarce.
      METHODS: We retrospectively reviewed the complete files of pediatric SLE patients
      from 1995 to 2010. All patients underwent kidney biopsy promptly after diagnosis.
      RESULTS: Thirty-six patients (10 males and 26 females) were enrolled. Mean age at
      diagnosis and observation period were 11.6 +/- 2.4 years and 8.1 +/- 4.4 years,
      respectively. Seven patients had AKI at onset of SLE. Compared with those without
      AKI, patients with AKI had significantly higher proportions of pathologically
      proliferative LN. Only one patient with AKI progressed to ESKD without complete
      recovery of renal function. Overall and renal survival rates were 100% and 97.2%,
      respectively. There was no significant difference in estimated glomerular
      filtration rate at the final visit (85.0 ml/min/1.73 m2 in the AKI group vs.
      103.2 ml/min/1.73 m2 in the non-AKI group; p = 0.11). CONCLUSIONS: Our study
      demonstrated favorable renal outcomes in childhood-onset LN with AKI in the near
      to midterm period. Inducing complete remission may be important for preserving
      renal function.

PMID- 30289014
TI  - Pharmacokinetics of mycophenolate mofetil in juvenile patients with autoimmune
      diseases.
AB  - OBJECTIVES: This study aimed to determine the association between the dosage and
      pharmacokinetics of mycophenolate mofetil (MMF) in juvenile patients with
      autoimmune diseases. METHODS: Totally, 29 patients were administered oral MMF.
      The blood concentrations of mycophenolate acid (MPA) at seven points, the area
      under the time-concentration curve (MPA-AUC0-12h), the peak concentration (Cmax),
      and the time to peak concentration (Tmax) were measured. To obtain a dose
      normalized MPA-AUC0-12h value, the actual measured MPA-AUC0-12h value was divided
      by the dose value of the morning administration corrected for body weight (BW) or
      body surface area (BSA). The patients were classified into three age groups
      (group 1, <=10 years; group 2, >10-<=15 years; and group 3, >15 years), and
      pharmacokinetic parameters were compared among the groups. RESULTS: In total, we
      obtained 37 measurements. The actual measured MPA-AUC0-12h values and the MPA
      AUC0-12h values corrected for dose per BW and Tmax were lower in young patients.
      The MPA-AUC0-12h values corrected for dose per BSA and Cmax were comparable among
      all the groups. CONCLUSIONS: In patients with juvenile autoimmune diseases,
      determining MMF administration dosage according to BSA may facilitate MPA-AUC0
      12h value prediction.

PMID- 30289015
TI  - Cold hypersensitivity after hand injuries. A prospective 7-year follow-up.
AB  - We studied changes in cold hypersensitivity from 3 to 7 years following severe
      hand injuries. Data was collected using postal questionnaires 7 years after
      injury in 71 patients who had participated in a 3-year follow-up from the time of
      injury. There was no change in cold sensitivity measured using the McCabe Cold
      Sensitivity Severity scale (CSS) from 3 to 7 years after injury. However, there
      was a trend toward decreased severity measured using a five-level scale of self
      reported cold hypersensitivity. Compared to the 3-year follow-up, fewer
      respondents rated their condition as severe and two patients had recovered from
      their cold hypersensitivity at the 7-year follow-up. Furthermore, 21 (30%) of the
      respondents stated a decrease in cold hypersensitivity during the last 2 years.
      Limitations in cold associated activities and the importance of being less
      limited in leisure activities (NRS 0-10) did not change between the two follow
      ups. In conclusion, the CSS-scores did not change from 3 to 7 years after injury.
      Several patients experienced improvements in cold hypersensitivity, but few
      recovered completely from the condition.

PMID- 30289016
TI  - A new screening tool for self-neglect in community-dwelling older adults: IMSelf
      neglect questionnaire.
AB  - OBJECTIVE: We aimed to develop a new screening tool for self-neglect in community
      dwelling self-sufficient older adults. METHODS: Istanbul Medical School Elder
      Self-Neglect questionnaire (IMSelf-neglect) was developed as a screening tool.
      Community-dwelling, self-sufficient older adults were recruited in a geriatric
      outpatient clinic (n = 226, 142 female, 84 male). Construct validity was based on
      social-worker's interview as a gold-standard method. The cut-off threshold for
      IMSelf-neglect questionnaire was calculated from ROC-analysis using cut-off
      values that predicted social-worker's opinion whether the older adult has self
      neglect. RESULTS: Mean age was 74 +/- 6.5 years. The inter-rater and test-retest
      reliability were excellent (r = 0.887, p < .05; r = 0.942, p < .05,
      respectively). The internal consistency was good (Cronbach's alpha: 0.708). Cut
      off threshold for IM Self-neglect questionnaire was calculated as 7 with 92.1%
      sensitivity and 70.7% specificity. Positive predictive value and negative
      predictive value of IMSelf-neglect questionnaire were 38.9% and 97.8%,
      respectively. There was significant moderate agreement between social worker's
      assessment and results of IMSelf-neglect questionnaire (kappa = 0.407, p < .001).
      The social worker confirmed 16.8% of the participants have self-neglect by the
      gold-standard clinical interview. Participants with self-neglect had decreased
      functionality, worse quality of life and tended to have more depression compared
      with participants without self-neglect. DISCUSSION/CONCLUSION: We developed the
      IMSelf-neglect questionnaire as a valid and reliable tool to screen self-neglect
      in outpatient clinics complementary to comprehensive geriatric assessment.

PMID- 30289017
TI  - Anti-vasospastic effects of botulinum toxin B pretreatment in animal models.
AB  - BACKGROUND: Botulinum toxin has been recently known for its vasodilatory effect.
      The main purpose of our study was to demonstrate the anti-vasospastic effect of
      botulinum toxin B in animal models. METHOD: In this prospective experimental rat
      study, we used 10 male Sprague-Dawley rats. The right and left inguinal areas
      (femoral vessels) served as the experimental and control groups, respectively.
      Three days prior to the experimental procedure, botulinum toxin B and normal
      saline were subcutaneously injected in the experimental and control groups,
      respectively. After three days, the vascular diameter and flow were measured.
      Then, phenylephrine was injected, and after one hour the same parameters were
      measured. RESULTS: The changes in arterial diameter in the experimental and
      control group were 30.83 +/- 10.43% and 40.00 +/- 8.61%, respectively. The vein
      diameter decreased by 22.98 +/- 10.08% in the experimental group compared to
      49.05 +/- 10.08% for the control group. Furthermore, the arterial flow change in
      the control group was 8.28 +/- 2.10% compared to 1.16 +/- 0.65% in the
      experimental group. In addition, the venous flow in the control group decreased
      by 9.27 +/- 2.75% compared to 0.92 +/- 0.56% in the experimental group. Both
      arterial and venous diameters and flows showed statistical significance between
      the experimental and control groups (p < .05). CONCLUSIONS: Our study
      demonstrated that pretreatment with botulinum toxin B led to significantly
      reduced change in vascular diameters and flows compared with the control group,
      supporting the anti-vasospastic effects of botulinum toxin B.

PMID- 30289018
TI  - The findings of musculoskeletal ultrasonography on primary Sjogren's syndrome
      patients in childhood with articular manifestations and the impact of anti-cyclic
      citrullinated peptide antibody.
AB  - OBJECTIVE: We researched the findings of musculoskeletal ultrasound sonography
      (MSUS) on primary Sjogren's syndrome in childhood (pSS-C) with articular
      manifestations. The correlation of rheumatoid factor (RF) and anti-cyclic
      citrullinated peptide antibody (ACPA) were investigated to evaluate the
      usefulness of MSUS on their articular prognosis. METHOD: The objective patients
      are pSS-C cases who visited our hospital complaining joint pain and/or joint
      swelling and for whom MSUS was performed. RESULT: Eight patients included 6
      female and 2 male, 5 RF-positive patients and 3 ACPA- positive patients. The mean
      age of onset was 11.1+/-3.0 years (352 physical joint findings and 284 MSUS
      findings The number of joints found clinical articular manifestations was 58/352
      joints, and arthritis detected by MSUS was 30/284 joints). In multivariate
      analysis, odds ratio of clinical articular manifestations was significant high in
      RF-positivity (2.9, 95%CI 1.5-6.2). Odds ratio of arthritis detected by MSUS in
      ACPA-positivity was significant high (3.7, 95%CI 1.5-11.6), although odds ratio
      in RF-positivity had no statistical significance. And a similar trend was seen in
      odds ratios of subclinical arthritis (4.9, 95%CI 1.6-18.0). CONCLUSION: It was
      indicated that MSUS is useful for pSS-C. ACPA-positive pSS-C patients have
      arthritis and subclinical arthritis more frequently than ACPA-negative patients.

PMID- 30289019
TI  - Cafeteria diet during lactation and/or post-lactation altered lipid profile/lipid
      peroxidation and increased anxiety-like behavior in male rat offspring.
AB  - OBJECTIVE: Evaluate the impact of the cafeteria diet during lactation and/or post
      lactation on physiological parameters and anxiety in the offspring of Wistar
      rats. METHODS: Male offspring of Wistar rats (n = 60) were randomized into four
      groups: Control (C), Lactation Cafeteria (LC), Post-lactation Cafeteria (PC) and
      Total Cafeteria (TC). Later in adult life the animals were submitted to the
      behavioral (elevated plus-maze and open field) and biological (body weight,
      consumption and food preference, glycemia, total cholesterol, LDL cholesterol,
      HDL cholesterol, VLDL cholesterol, triglycerides, total proteins, urea,
      creatinine, bilirubin, serum glutamic oxaloacetic transaminase, serum glutamic
      pyruvic transaminase, serum protein, and oxidative stress) evaluations. The data
      were submitted to ANOVA, followed by the Newman-Keuls test (p < 0.05). RESULTS:
      Animals treated with the cafeteria diet presented greater weight measurements
      compared to the control group. Triglyceride levels were higher in the PC group
      than in the other groups. MDA levels were higher in the PC and TC group than CL
      and C. The animals of the PC and TC groups presented higher levels of anxiety
      compared to the C and LC groups. No significant differences due to diet were
      observed in the locomotor and exploratory behaviors. CONCLUSIONS: The cafeteria
      diet ingestion was capable of triggering biological and behavioral alterations in
      rats.

PMID- 30289021
TI  - Semiparametric Bayesian kernel survival model for evaluating pathway effects.
AB  - Massive amounts of high-dimensional data have been accumulated over the past two
      decades, which has cultured increasing interests in identifying gene pathways
      related to certain biological processes. In particular, since pathway-based
      analysis has the ability to detect subtle changes of differentially expressed
      genes that could be missed when using gene-based analysis, detecting the gene
      pathways that regulate certain diseases can provide new strategies for medical
      procedures and new targets for drug discovery. Limited work has been carried out,
      primarily in regression settings, to study the effects of pathways on survival
      outcomes. Motivated by a breast cancer gene-pathway data set, which exhibits the
      "small n, large p" characteristics, we propose a semiparametric Bayesian kernel
      survival model (s-BKSurv) to study the effects of both clinical covariates and
      gene expression levels within a pathway on survival time. We model the unknown
      high-dimensional functions of pathways via Gaussian kernel machine to consider
      the possibility that genes within the same pathway interact with each other. To
      address the multiple comparisons problem under a full Bayesian setting, we
      propose a similarity-dependent procedure based on Bayes factor to control the
      family-wise error rate. We demonstrate the outperformance of our approach under
      various simulation settings and pathways data.

PMID- 30289020
TI  - The Self-Assessed Bekesy Procedure: Validation of a Method to Measure
      Intelligibility of Connected Discourse.
AB  - In clinical practice and research, speech intelligibility is generally measured
      by instructing the participant to recall sentences. Although this is a reliable
      and highly repeatable measure, it cannot be used to measure intelligibility of
      connected discourse. Therefore, we developed a new method, the self-assessed
      Bekesy procedure, which is an adaptive procedure that uses intelligibility
      ratings to converge to a person's speech reception threshold. In this study, we
      describe the new procedure and the validation in young, normal-hearing listeners.
      First, we compared the results on the self-assessed Bekesy procedure to a recall
      procedure for standardized sentences. Next, we evaluated the inter- and
      intrasubject variability of our procedure. Furthermore, we compared the
      thresholds for sentences in three masker types between the self-assessed Bekesy
      and a recall procedure to verify if these procedures resulted in similar
      conclusions. Finally, we compared the thresholds for two types of sentences and
      commercial recordings of stories. In general, the self-assessed Bekesy procedure
      is shown to be a valid and reliable procedure as similar thresholds (difference <
      1 dB) and test-retest reliability (< 1.5 dB) were observed compared with standard
      speech audiometry tests. In addition, the time efficiency and similar differences
      between maskers to a recall procedure support the potential of this procedure to
      be implemented in research. Finally, significant differences between the
      thresholds of sentences and connected discourse materials were found, indicating
      the importance of controlling for differences in intelligibility when presenting
      these materials at the same signal-to-noise ratios or when comparing studies.

PMID- 30289022
TI  - Giving Back Is Receiving: The Role of Generativity in Successful Aging Among HIV
      Positive Older Adults.
AB  - OBJECTIVES: Successful aging has been identified as an important emphasis for
      people living with human immunodeficiency virus (HIV). Little is known about how
      this population conceptualizes aging successfully and how this relates to
      generativity. This qualitative study examined the importance of generativity
      among 30 HIV-positive older adults to determine the role of generativity in
      successful aging. METHOD: Participants aged 50+ years were recruited in Ontario,
      Canada, through acquired immunodeficiency syndrome (AIDS) service organizations,
      clinics, and community agencies. Qualitative interviews were analyzed to explore
      strategies participants employed to engage in successful aging within their own
      personal context. RESULTS: Participants saw themselves as pioneers and mentors,
      helping others to navigate the landscape of aging with HIV. Four themes were
      identified through consensus including (a) reciprocity, (b) mentoring, (c)
      pioneerism, and (d) connecting through volunteerism. DISCUSSION: Interventions
      that promote intergenerational connections, community involvement, and generative
      acts within the HIV community can facilitate successful aging among older adults
      living with HIV/AIDS.

PMID- 30289023
TI  - Narrating ethnicity and diversity in Middle Eastern national genome projects.
AB  - Most Middle Eastern populations outside Israel have not been represented in
      Western-based international human genome sequencing efforts. In response,
      national-level projects have emerged throughout the Middle East to decode the
      Arab, Turkish and Iranian genomes. The discourses surrounding the 'national
      genome' that shape scientists' representation of their work to local and
      international audiences evoke three intersecting analytics of nationalism:
      methodological, postcolonial and diasporic. Methodologically, ongoing human
      genome projects in Turkey and Iran follow the population logics of other national
      and international genome projects, for example justifying research with reference
      to projected health benefits to their fellow citizens. Meanwhile, assumptions
      about and representations of ethnicity and diversity are deeply inflected by
      local histories of scientific development and nationalist politics. While Iranian
      geneticists have transformed this paradigm to catalog national genetic diversity
      through a discourse of 'Iranian ethnicities', Turkish geneticists remain
      politically constrained from acknowledging ethnic diversity and struggle to
      distance their work from racialized narratives of Turkish national identity. Such
      nationally-framed narratives of genomic diversity are not confined to their
      original contexts, but travel abroad, as demonstrated by a US-based genome
      project that articulates a form of Iranian-American diasporic nationalism.

PMID- 30289024
TI  - "I Asked Myself If I Would Ever Love My Baby": Mothering Children Born of
      Genocidal Rape in Rwanda.
AB  - The 1994 Rwandan genocide was characterized by brutal acts of widespread sexual
      violence against women that, for some, led to unwanted pregnancy, childbirth, and
      motherhood. This study explores the perspectives and experiences of 44 Rwandan
      women with children born of genocidal rape through in-depth qualitative
      interviews. Emerging from the data are the themes of identity and belonging,
      ambivalence, and truth-telling in the mother-child relationship. Findings
      highlight the lasting and intergenerational legacy of genocidal rape, and
      practice and policy implications are discussed.

PMID- 30289025
TI  - Determining energy requirement and evaluating energy expenditure in neurological
      diseases.
AB  - OBJECTIVES: It has been reported that in most neurological patients, resting
      energy expenditure due to hypermetabolism is increased. Physical activity, which
      is another component of energy expenditure, varies depending on the course of the
      disease. Different mechanisms are used to explain changes in energy expenditure
      in this population. Pathological problems of centers that regulate energy balance
      in the brain, endocrine and metabolic dysfunction, mitochondrial damage,
      autonomic dysfunction and inflammatory anomalies are thought to be at the root of
      this situation. In this review study, studies about energy expenditure and energy
      requirement in neurological diseases have been examined and suggested practices
      in this field have been presented. METHODS: We reviewed articles regarding
      selected from PubMed, Science Direct, EBSCO, and databases about energy
      expenditure and neurological diseases. RESULTS: Based on the type of neurological
      diseases; factors such as stage of the disease, disease complications, metabolic
      status, mechanical ventilation, body composition, movement restrictions or
      hyperactivity change energy expenditure and, as a result, nutrition requirement.
      Determination of the energy requirement is the basic variable for adjusting
      medical nutrition therapy. Despite an increase in resting energy expenditure as a
      result of metabolic processes in most neurological disorders, the daily energy
      expenditure is reported to change based on the restriction of physical activity
      due to the disorder. DISCUSSION: Determining patient's energy expenditure and
      energy requirements is regarded as the right approach in terms of improving the
      patient's quality of life, regulating appropriate medical nutrition treatment and
      increasing the effectiveness of other treatments.

PMID- 30289026
TI  - The pharmacodynamic profile of "Blackadder" blackcurrant juice effects upon the
      monoamine axis in humans: A randomised controlled trial.
AB  - Emerging evidence from human intervention trials indicates health benefits of
      consuming blackcurrant fruit, including improvements to cognitive performance,
      modulation of blood flow, regulation of blood glucose and inhibition of enzymes
      underpinning normal cognitive function. Of particular relevance is our previous
      demonstration of monoamine oxidase (MAO)-A and B inhibition after the consumption
      of a New Zealand "Blackadder" blackcurrant juice in humans. The current study
      uses a double-blind, placebo-controlled, randomised cross- over design to assess
      the pharmacodynamics of the effects on platelet MAO-B inhibition and associated
      substrates, plasma prolactin levels and blood glucose levels after consumption of
      a single serve of "Blackadder" blackcurrant juice standardised to 500 mg
      polyphenols. Eight healthy male (20--35 years) participants completed the trial.
      Measurements were obtained at baseline 15, 30, 45, 60, 100, 120, 150, 180, 240
      mins and 24 h post dose. A fast, absolute and reversible inhibition of blood
      platelet MAO-B (P < 0.001) and a significant but delayed reduction in plasma
      prolactin (P < 0.001) were observed following the consumption of "Blackadder"
      blackcurrant juice when compared to a placebo control. No interpretable changes
      in substrates of MAO or associated metabolites were seen. These data provide a
      clear time course of the reversible inhibition of MAO-B after the single
      consumption of a of New Zealand "Blackadder" blackcurrant juice standardised at
      500 mg of polyphenols and, therefore, provide a therapeutic window on which to
      base future nutritional interventions.

PMID- 30289027
TI  - On mountains and prophets: targeting majorities to support minorities by using
      norm-critics in health education.
AB  - This debate article advocates for norm-critics instead of empowering coping and
      pedagogy of tolerance as an educational approach to mitigate stigmatization as
      well as blame and guilt for health-deviant minorities within the field of health
      disparities. Norm-critics is a way of making members of the (presumably healthy)
      normative majority uncover and question their health-related norms and raise
      awareness for the processes by which members of that majority re/construct images
      of stereotypic figures (such as "the fatso" or "the couch-potato") with certain
      personal character traits which are to be condemned and, in doing so, limit the
      acting space of those identified as examples of those figures. The approach, its
      theoretical background, arguments promoting norm-critics, and some suggestions
      for its practical application are presented. It is concluded that norm-critics
      render a valuable and much needed addition to the health intervention repertoire.

PMID- 30289028
TI  - Do mental health patients learn what their cognitive-behaviour therapists think
      they do? A short report on qualitative interviews comparing perspectives.
AB  - PURPOSE: The acquisition of skills is essential to the conceptualization of
      cognitive-behavioural therapy. Yet, what experiences are encountered and what
      skills actually learned during therapy, and whether patients and therapists have
      concurrent views hereof, remains poorly understood. METHOD: An explorative pilot
      study with semi-structured, corresponding interview guides was conducted. Pilot
      data from our outpatient unit were transcribed and content-analyzed following
      current guidelines. RESULTS: The responses of 18 participants (patients and their
      psychotherapists) were assigned to six main categories. Educational and cognitive
      aspects were mentioned most frequently and consistently by both groups. Having
      learned Behavioural alternatives attained the second highest agreement between
      perspectives. CONCLUSIONS: Patients and therapists valued CBT as an opportunity
      to learn new skills, which is an important prerequisite also for the maintenance
      of therapeutic change. We discuss limitations to generalizability but also
      theoretical and therapy implications.

PMID- 30289029
TI  - Parents' experiences with sleep problems in children aged 1-3 years: a
      qualitative study from a health promotion perspective.
AB  - PURPOSE: The aim of this study was to explore the experiences of parents whose
      children aged 1-3 years have sleep problems, from a health promotion perspective.
      METHODS: This was a qualitative study, based on semi-structured interviews with
      12 mothers in Norway. The material was analysed by qualitative content analysis.
      RESULTS: Parents experienced problems with getting their children to bed, getting
      them to fall asleep, and episodes of awakening at night. Parents expressed that
      it was time-consuming and difficult to teach their children sleep regulation.
      Parents handled the sleep problems through the following coping strategies:
      acknowledging challenges, clarifying one's self-understanding, implementing
      change measures, and safeguarding family well-being. These coping strategies
      resulted in this main theme: the health-promoting regulation of interactions,
      including parents' strengthening of sleep regulation in their small children and
      the safeguarding of well-being in the family. CONCLUSIONS: Early, individually
      customized guidance for parents, with a focus on revealing and acknowledging
      their experiences with sleep problems in children, is essential for parents to
      find opportunities to cope with such challenges. Appropriate goals seem to be
      important for them to succeed in strengthening sleep regulation in their children
      in a more satisfactory way.

PMID- 30289030
TI  - Energy flux: staying in energy balance at a high level is necessary to prevent
      weight gain for most people.
AB  - Energy flux, the rate of energy conversion from absorption to expenditure or
      storage, is a critical component of understanding weight management. Individuals
      who maintain body weight over time have common characteristics including a
      relatively high level of physical activity and minimal changes in body
      composition, muscle mass and metabolic rate. A higher state of energy flux
      resulting from high energy expenditure may provide for a greater 'sensitivity'
      between energy intake and expenditure. This sensitivity stabilizes body weight by
      enhancing reciprocal compensation among these components with changes in eating
      or activity. The energy balance framework suggests that a higher level of energy
      expenditure requires higher energy intake to maintain body mass. Maintaining
      energy balance at a higher caloric intake and expenditure should be a more
      successful long-term strategy for weight maintenance than reduced consumption or
      extreme caloric restriction at a low level of energy expenditure (a low energy
      flux) and improve intervention effectiveness for sustainable methods for body
      weight stability.

PMID- 30289031
TI  - The impact of fibroblast growth factor-23 on the cardiovascular system in chronic
      kidney disease.
AB  - Chronic kidney disease is associated with an accelerated risk of cardiovascular
      (CV) mortality. Seminal work over the last decade has identified abnormal bone
      metabolism as an important modulator of the increased CV burden in this cohort.
      In particular, FGF23, a phosphaturic hormone with serum levels found to be
      markedly elevated in chronic kidney disease, is independently associated with
      increased risks of all-cause mortality and CV events. This editorial will discuss
      the proposed mechanisms linking FGF23 to CV disease in chronic kidney disease,
      namely, direct cardiac myocyte toxicity, endothelial dysfunction and vascular
      calcification.

PMID- 30289032
TI  - Relevance, pathogenesis and clinical implications of thyroid disorders in
      children with celiac disease.
AB  - Celiac disease is a frequent chronic inflammatory small bowel disease which may
      present itself with associated autoimmune comorbidities. Among these
      comorbidities, thyroid disorders show a significant prevalence; even in the
      pediatric population. However, the exact epidemiology and clinical significance
      of such alterations are yet to be fully elucidated. The most updated guidelines
      do not currently offer any specific support. Focusing on the pediatric
      population, we will review the recent available literature that we believe might
      be helpful in advancing the clinician's knowledge-base regarding this issue. We
      also discuss which, to our knowledge, are the key pathophysiologic concepts
      behind the association between these two entities. Finally, we offer our own
      clinical perspective, recommending routine laboratory thyroid screening, possibly
      followed by an echographic thyroid evaluation as we believe such an approach to
      be appropriate when caring for children with celiac disease.

PMID- 30289033
TI  - Elosulfase alfa for the treatment of mucopolysacchoridosis IVA.
AB  - Mucopolysacchariodosis IVA is a lysosomal storage disorder characterized by
      deficiency of the enzyme N-acetylgalactosamine-6-sulfatase leading to
      accumulation of glycosaminoglycans. Mucopolysacchariodosis IVA affects many
      organs, especially the skeletal system. The disease is progressive, leads to
      serious cardiopulmonary problems and is severely debilitating. Enzyme replacement
      therapy with elosulfase alfa is the only approved treatment for this rare genetic
      condition. The results from a Phase III clinical trial demonstrated that
      elosulfase alfa at dose 2.0 mg/kg weekly given intravenously improved the walking
      distance in 6 min. The results of the 3-min stair climb test and respiratory
      function test did not show statistically significant improvement over the
      placebo. However, the composite end point analysis combining changes from
      baseline in walking distance in 6 min, 3-min stair climb test and respiratory
      function showed that at dose 2.0 mg/kg weekly, subjects performed better than the
      placebo, indicating that the effects of treatment are clinically meaningful.
      Serious side effects are uncommon and infusion-associated reactions are
      manageable.

PMID- 30289034
TI  - Dulaglutide, a GLP-1 receptor agonist, for the treatment of type 2 diabetes.
AB  - The prevalence of diabetes continues to rise worldwide. Over the past five years,
      available treatment options have expanded to allow individualized management of
      patients with diabetes. The glucagon-like peptide-1 (GLP-1) receptor agonists
      have become an essential tool in the management of type 2 diabetes mellitus
      (T2DM). This class provides several advantages for glycemic control with minimal
      risk of hypoglycemia. Based on the most recent guidelines for T2DM, GLP-1
      receptor agonists can be prescribed as monotherapy or in combination with oral
      antidiabetic agents or insulin for the management of T2DM. Dulaglutide has become
      the most recent and available GLP-1 receptor agonist on the market. Dulaglutide
      is a once-weekly GLP-1 receptor agonist that can be used as monotherapy or as a
      second-line agent for T2DM. This review article summarizes the efficacy, safety,
      and clinical attributes of dulaglutide among patients with T2DM.

PMID- 30289035
TI  - Sodium-glucose co-transporter 2 inhibitors: evidence and place in therapy.
AB  - Type 2 diabetes effects millions of people yet remains difficult to treat with
      oral pharmacotherapy. Metformin is the first line recommended therapy, and
      current guidelines suggest individualized therapy for second line selection.
      Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are the newest class of
      agents in treating type 2 diabetes via an insulin independent mechanism to lower
      blood glucose. Currently marketed agents, including canagliflozin, dapagliflozin,
      empagliflozin, and luseogliflozin, reduce hemoglobin A1c (HbA1c) ~0.8-1%, reduce
      fasting and post prandial glucose, and have little hypoglycemia associated with
      them when added to therapies including metformin, a sulfonylurea, pioglitazone,
      or insulin. Patients receiving SGLT-2 inhibitors have reduced weight and blood
      pressure, but are more susceptible to urinary tract infections and genital
      mycotic infections. This review summarizes current literature regarding the SGLT
      2 inhibitors.

PMID- 30289036
TI  - Effects of anti-diabetic drugs on bone metabolism.
AB  - An increased fracture risk is observed in Type 1 and Type 2 diabetic patients.
      Although diabetes-related complications are important in the etiology of bone
      fracture in diabetes, the effect of anti-diabetic medications should not be
      neglected. Indeed, many drugs used commonly to treat diabetes can interfere with
      bone physiology, resulting in a positive or negative impact on skeletal health.
      The aim of the present review is to summarize the current evidence on the effects
      of anti-diabetic drugs on bone.

PMID- 30289037
TI  - Diagnosis, treatment and clinical perspectives of acromegaly.
AB  - Acromegaly is an insidious disease of the pituitary caused by a growth hormone
      secreting adenoma. Generally, the diagnosis is made rather late in the course of
      the disease. Currently, acromegaly can be cured in about half of the patients
      with the disease by expert surgery. The remainder of non-surgically cured
      patients often can be effectively treated with somatostatin analogs; either with
      the new generation of dopaminergic drugs or with Pegvisomant, a GH-receptor
      blocking agent. However, at the time of diagnosis many patients suffer from
      serious comorbidities, including hypertension, heart disease, arthrosis, sleep
      apnea and diabetes mellitus. Recent reports have shown that mortality risk can be
      normalized. Nevertheless, all efforts should be undertaken to treat
      comorbidities. New strategies for surgery and medical treatment are discussed.

PMID- 30289038
TI  - Precocious pubertal development: a challenge for pediatric endocrinologists.
AB  - Precocious puberty is one of the most common conditions encountered in the
      pediatric endocrinology clinic and can be defined as the appearance of secondary
      sexual characteristics in girls under 8 years and boys under 9 years of age. The
      timing of pubertal onset has received increasing attention because of a reported
      gradual decline in age at menarche in most populations. Proposed mechanisms for
      these changes include: an improvement in socioeconomic conditions with consequent
      increased nutritional status and a rise in a number of environmental pollutants.
      The challenges for pediatric endocrinologists are increasing: what are the
      mechanisms of precocious puberty in modern society? Should our diagnostic
      criteria be changed? When to treat? What are the consequences of treatment?
      Little is known of the short and long term consequences of GnRH-analog treatment,
      especially in terms of psychological consequences for children and their
      families.

PMID- 30289039
TI  - Recommendations for hormone therapy in hysterectomized women: importance of new
      data in clinical management.
AB  - Women with a prior hysterectomy with and without oophorectomy represent special
      cohorts among those who require menopausal hormone therapy (HT), as a progestogen
      is not required for endometrial protection. This is relevant in light of recent
      research demonstrating superiority of estrogen therapy alone compared with
      estrogen plus a progestogen with respect to breast cancer risk and perhaps even
      cardiovascular protection. No longer is it appropriate to lump all HT regimens
      together when advising patients. Unfortunately, there is a general reluctance in
      the healthcare community to prescribe HT even a decade after publication of the
      results of the Women's Health Initiative trial. However, with subsequent research
      showing a favorable benefit/risk balance of short-term estrogen therapy in
      symptomatic, recently menopausal women, especially those who have undergone
      hysterectomy with oophorectomy, the need for educating patients and providers on
      the matter cannot be overemphasized.

PMID- 30289040
TI  - Science of premix insulin: where have we reached?
AB  - Diabetes is a progressive disease and by achieving and maintaining optimal
      glycemic control, the onset of complications can be prevented or delayed. Insulin
      is most effective at any stage of diabetes. Although basal-bolus therapy is the
      gold standard treatment, it has its own limitations such as multiple pricks,
      close monitoring and cost. Premixed insulin on the other hand is convenient,
      requires fewer injections, is a single device and delivers both the basal and
      bolus component till the next meal. Although premixed insulin analogs have the
      advantages of mealtime flexibility, compliance and better post-prandial glucose
      control, no significant differences have been observed in HbA1c reduction and
      overall hypoglycemia when compared to premixed human insulin. This review will
      attempt to analyze the efficacy, safety and limitations of currently available
      premix human insulin and premix analogs including recent advancements in the
      area.

PMID- 30289041
TI  - Heterogeneity in diabetes-associated autoantibodies and susceptibility to Type 1
      diabetes: lessons for disease prevention.
AB  - Autoantibodies against pancreatic islets are strong predictors of Type 1
      diabetes. When persistent beta-cell autoantibodies against at least two
      autoantigens are detected, the probability of diabetes is extremely high,
      although the time period before disease development can vary from days up to more
      than 20 years. Insulin autoantibodies or antibodies specific to glutamate
      decarboxylase 65 enzyme are in most cases, the first autoantibodies to appear.
      Insulin autoantibodies typically emerge very early with a peak at the age of 1.5
      years, whereas the onset of glutamic acid decarboxylase 65 antibody positivity
      has a more even distribution, peaking later in childhood. These differences in
      the timing of appearance suggest that different environmental factors might be
      involved in the initiation of beta-cell autoimmunity beginning either already in
      infancy or later on. This should be taken into account in studies aimed at
      identifying environmental factors triggering islet cell-specific autoimmunity and
      also in the design of prevention trials.

PMID- 30289042
TI  - The non-glycemic effects of incretin therapies on cardiovascular outcomes,
      cognitive function and bone health.
AB  - The incretin therapies, glucagon-like peptide-1 receptor agonists and dipeptidyl
      peptidase-4 inhibitors, have been developed to lower blood glucose levels in
      patients with Type 2 diabetes. However, in addition to being a treatment strategy
      to improve metabolic control, incretin therapies have shown effects independent
      of glycemic control, including the potential to positively impact cardiovascular
      events, cognitive deficits and bone mineral density. This paper outlines the non
      glycemic effects of incretin therapies on cardiovascular disease, cognitive
      function and bone health.

PMID- 30289043
TI  - Future challenges for pediatric diabetes management in developing countries:
      lessons from Africa.
AB  - In this review, we describe the epidemiology of diabetes mellitus in children and
      adolescents in Africa, noting that there is a paucity of data with regard to the
      burden of disease, prevalence of undiagnosed diabetes, healthcare and acute and
      chronic complications. Furthermore, access to care remains an issue of great
      concern. Our view is that in the next 5 years, more research will be undertaken
      on the burden of the disease and on interventions to provide better access to
      care. While the majority of African countries still have a low incidence of
      diabetes in children, it is predicted that the incidence will increase and it is
      therefore essential that governments develop sustainable policies to deal with
      such increases.

PMID- 30289044
TI  - Luteinizing hormone and human chorionic gonadotropin: a review of their varied
      clinical applications in assisted reproductive technology.
AB  - Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are often viewed
      as interchangeable from a functional standpoint because they are highly
      homologous members of the same glycoprotein hormone family that share a common
      alpha-subunit and receptor. However, technological advances yielding highly
      purified and recombinant gonadotropin preparations have revealed that LH and hCG
      fulfill different roles, both endogenously and when administered exogenously.
      These differences are becoming more apparent as the individual hormones are
      incorporated into the treatment of infertility - a therapeutic area that is
      continually advancing with the introduction of new agents and emerging clinical
      trial data. This review examines the unique attributes of LH and hCG that drive
      their distinctive applications in the treatment of female infertility.

PMID- 30289045
TI  - Insulin, carbohydrate restriction, metabolic syndrome and cancer.
AB  - We propose that dietary carbohydrate restriction, particularly ketogenic diets,
      may provide benefit as a therapeutic or preventive strategy in cancer, alone or
      as an adjunct to pharmacology. The argument derives from several points of
      evidence: There is a close association between cancer and both diabetes and
      obesity. Extensive evidence shows that low carbohydrate diets are the most
      effective dietary treatment of Type 2 diabetes and dietary adjunct in Type 1.
      Such diets also target all the markers of metabolic syndrome. Finally, de facto
      reduction in carbohydrate likely contributes to total dietary restriction, which
      is effective in the prevention and treatment of cancer. The idea is consistent
      with recent interest in treating cancer with drugs that target diabetes. To move
      forward, we must understand obesity and diabetes as response to a hyperglycemic
      state rather than simply a cause of downstream effects.

PMID- 30289046
TI  - Applying emerging science to contraception research: implications for the clinic.
AB  - Emerging science will make an important contribution towards the development of
      improved contraceptives. While long-acting reversible contraceptives remain the
      most effective method, new user-controlled, mid-acting methods will avoid the
      need for procedures requiring trained providers. Contraceptives combined with
      other agents may bring additional health benefits, such as dual protection
      against both pregnancy and sexually transmitted infections. Emerging research
      areas in proteomics allowed the discovery of new reproductive targets that may
      lead to non-hormonal contraceptives for both men and women. Current research
      objectives include the improvement of existing contraceptive methods, as well as
      discovery of new materials able to deliver new molecules more specifically to
      their target without systemic actions.

PMID- 30289047
TI  - Molecular genetic advances in pituitary tumor development.
AB  - Pituitary adenomas are a heterogeneous group of tumors that may occur as part of
      a complex syndrome or as an isolated endocrinopathy and both forms can be
      familial or non-familial. Studies of syndromic and non-syndromic pituitary
      adenomas have yielded important insights about the molecular mechanisms
      underlying tumorigenesis. Thus, syndromic forms, including multiple endocrine
      neoplasia type 1 (MEN1), MEN4, Carney Complex and McCune Albright syndrome, have
      been shown to be due to mutations of the tumor-suppressor protein menin, a cyclin
      dependent kinase inhibitor (p27Kip1), the protein kinase A regulatory subunit 1
      alpha, and the G-protein alpha-stimulatory subunit (Gsalpha), respectively. Non
      syndromic forms, which include familial isolated pituitary adenoma (FIPA) and
      sporadic tumors, have been shown to be due to abnormalities of: the aryl
      hydrocarbon receptor-interacting protein; Gsalpha; signal transducers; cell cycle
      regulators; transcriptional modulators and miRNAs. The roles of these molecular
      abnormalities and epigenetic mechanisms in pituitary tumorigenesis, and their
      therapeutic implications are reviewed.

PMID- 30289048
TI  - Implementing a low-carbohydrate, ketogenic diet to manage type 2 diabetes
      mellitus.
AB  - INTRODUCTION: Type 2 diabetes mellitus (T2DM) has reached epidemic proportions in
      the modern world. For individuals affected by obesity-related T2DM, clinical
      studies have shown that carbohydrate restriction and weight loss can improve
      hyperglycemia, obesity, and T2DM. Areas covered: Reducing carbohydrate intake to
      a certain level, typically below 50 g per day, leads to increased ketogenesis in
      order to provide fuel for the body. Such low-carbohydrate, ketogenic diets were
      employed to treat obesity and diabetes in the 19th and early 20th centuries.
      Recent clinical research has reinvigorated the use of the ketogenic diet for
      individuals with obesity and diabetes. Although characterized by chronic
      hyperglycemia, the underlying cause of T2DM is hyperinsulinemia and insulin
      resistance, typically as a result of increased energy intake leading to obesity.
      The ketogenic diet substantially reduces the glycemic response that results from
      dietary carbohydrate as well as improves the underlying insulin resistance. This
      review combines a literature search of the published science and practical
      guidance based on clinical experience. Expert commentary: While the current
      treatment of T2DM emphasizes drug treatment and a higher carbohydrate diet, the
      ketogenic diet is an effective alternative that relies less on medication, and
      may even be a preferable option when medications are not available.

PMID- 30289049
TI  - Prospective bi-directional associations between sedentary time and physical
      activity with cognitive performance: a cohort study.
AB  - This prospective study determined whether: (1) objective physical activity (PA)
      and sedentary (SED) time at 9 years was associated with cognition at 15 years,
      (2) cognition at 9 years was associated with PA and SED at 15 years, and (3) the
      change in PA and SED from 9 to 15 years was associated with the change in
      cognition. Cognitive performance was assessed from picture vocabulary, verbal
      analogy, passage comprehension, and applied problem tasks. Regression models were
      used to explore each aim while adjusting for covariates. Among the combined
      sample, SED (min. day-1) at 9 years was unrelated with cognitive performance at
      15 years, whereas participating in >= 60 min. day-1 of moderate-to-vigorous PA
      (MVPA) at 9 years predicted lower cognitive scores at 15 years. In the reverse
      direction, cognitive performance at 9 years was unrelated with SED and MVPA (min.
      day-1) at 15 years. Over 6 years, increased SED (min. day-1) predicted lower
      improvement to verbal analogy scores (B = -0.01, p = 0.028). In comparison, an
      increase (or relatively smaller decline) in MVPA (min. day-1) predicted greater
      improvement in applied problem scores (B = 0.06, p = 0.007). Contextual
      information regarding SED and MVPA behavior would help understand bi-directional
      associations of activity and cognition.

PMID- 30289050
TI  - Characteristics, behaviours and readiness of persons seeking hearing healthcare
      online.
AB  - This study describes characteristics, behaviours and readiness of people who are
      interested in seeking hearing healthcare (HHC) online. A non-profit clinic was
      established from which services through a virtual clinic are offered. Most of the
      patient-audiologist interactions are conducted online. We used online means to
      invite individuals to take a free online digit-in-noise (DIN) test. Upon failing
      the test, individuals reported their readiness to seek HHC by using two tools:
      the line and the staging algorithm. Individuals >=18 years of age, within the
      greater Durban area, South Africa, were eligible to participate in the study. A
      total of 462 individuals completed the online DIN test during the first 3 months.
      Of those, 58.66% (271/462) failed the test and 11.04% (51/462) submitted their
      details for further contact from the clinic audiologist. Five individuals
      proceeded to a comprehensive hearing evaluation and hearing aid trial: all those
      individuals showed readiness to seek further HHC on the measurement tools. These
      individuals have reported knowing of their hearing challenges prior to taking the
      test and have waited for a period of between 5 and 16 years before seeking HHC. A
      significant association between age and DIN test result was found. This
      explorative study is the first clinic to utilise digital tools across the entire
      patient journey in combination with face-to-face interactions in providing HHC.
      Internet-connected devices provide an opportunity for individuals to seek HHC and
      for providers to offer initial services to detect, counsel and support persons
      through the initial engagement process of seeking HHC. This may open up new
      audiology patient pathways through online hearing screening, assessment of
      readiness to seek further HHC and enhancement of service delivery using hybrid
      services by combining online and face-to-face modes of synchronous and
      asynchronous communication.

PMID- 30289051
TI  - Adolescent attachment insecurity and the influence of MBT.
AB  - The aim of this study in a high-risk adolescent sample with personality disorders
      receiving intensive mentalisation-based treatment (MBT), was first, to examine
      deviations in insecure attachment distribution of the normative pattern, and in
      borderline personality disorder and other personality disorders; second, to
      explore whether MBT alters attachment representations and whether these
      alterations are related to changes in psychological distress. A total of 60
      adolescents were investigated pre-treatment for both categorical and continuous
      measures of the Adult Attachment Interview (AAI). Pre- and post-AAI (N = 33) data
      were compared with psychological distress measured by the Symptom Checklist-90.
      While the most disturbed category of insecure attachment, the "cannot classify"
      category, was overrepresented (46.7%) at pre-treatment, no differences were
      observed by type of personality disorder. At post-treatment, 48.5% of the
      participants showed positive change in the attachment representation, and their
      psychological distress lowered significantly (p = .002). The whole sample
      demonstrated change towards increased secure attachment (z = -2.85, p = .004).
      Attachment insecurity was found in all adolescent personality disorders which MBT
      seemed to be able to alter. However, as we included no control group, we cannot
      conclude that changes are due to the treatment itself.

PMID- 30289052
TI  - Management and prognosis of cancers in the accessory parotid gland.
AB  - Objective This study was performed to analyze the clinical management of
      accessory parotid gland (APG) cancer and possible risk factors for disease
      related death. Methods Patients diagnosed with primary APG cancers in the largest
      medical center in Northeast China were enrolled from January 1990 to December
      2016. Results All 43 patients underwent resection of the tumors and superficial
      parotid gland by a standard Blair incision. Seven (16.3%) patients also required
      selective neck dissection. The most common lesion was mucoepidermoid carcinoma.
      Temporary facial paralysis occurred in 11 (25.6%) patients, and permanent facial
      paralysis occurred in 3 (7.0%) patients because of surgical resection of the
      facial nerve, which was involved with the tumor. The 5- and 10-year disease
      specific survival rates were 86.0% and 66.0%, respectively. The tumor stage, neck
      status, neck dissection, and tumor grade were significantly associated with
      disease-related death, but only the tumor grade was an independent risk factor.
      Conclusion Superficial parotidectomy is a reliable surgical procedure associated
      with a high survival rate and low morbidity in treating APG cancers. The tumor
      grade is the key prognostic factor.

PMID- 30289053
TI  - Multimodal antidepressant vortioxetine causes analgesia in a mouse model of
      chronic neuropathic pain.
AB  - Vortioxetine is a multimodal antidepressant that potently antagonizes 5-HT3
      serotonin receptors, inhibits the high-affinity serotonin transporter, activates
      5-HT1A and 5-HT1B receptors, and antagonizes 5-HT1D and 5-HT7 receptors. 5-HT3
      receptors largely mediate the hyperalgesic activity of serotonin that occurs in
      response to nerve injury. Activation of 5-HT3 receptors contributes to explain
      why selective serotonin reuptake inhibitors, such as fluoxetine, are not
      indicated in the treatment of neuropathic pain. Here, we studied the analgesic
      action of vortioxetine in the chronic constriction injury model of neuropathic
      pain in mice. Vortioxetine was injected once a day for 27 days at doses (10
      mg/kg, intraperitoneally) that determine >90% 5-HT3 receptor occupancy in the
      central nervous system. The action of vortioxetine was compared to the action of
      equal doses of the serotonin-noradrenaline reuptake inhibitor, venlafaxine (one
      of the gold standard drugs in the treatment of neuropathic pain), and fluoxetine.
      Vortioxetine caused a robust analgesia in chronic constriction injury mice, and
      its effect was identical to that produced by venlafaxine. In contrast, fluoxetine
      was inactive in chronic constriction injury mice. Vortioxetine enhanced
      mechanical pain thresholds in chronic constriction injury mice without changing
      motor activity, as assessed by the open-field and horizontal bar tests. None of
      the three antidepressants caused analgesia in the complete Freund's adjuvant
      model of chronic inflammatory pain. These findings raise the attractive
      possibility that vortioxetine can be effective in the treatment of neuropathic
      pain, particularly in patients with comorbid depression and cognitive
      dysfunction.

PMID- 30289055
TI  - Mapping and driving the stem cell ecosystem.
AB  - The stem cell and regenerative medicine arena has become increasingly complicated
      in recent years with thousands of people involved. There are as many as a dozen
      or more main groups of stakeholders, who together may be viewed as one ecosystem
      that is now rapidly evolving. The nature of the ecosystem and its evolution have
      major implications for not just those within it, but also for medicine and
      society at large. Here, I describe this ecosystem and its evolution, as well as
      the negative impacts within the ecosystem of a constellation of hundreds of
      unproven for-profit clinics and related businesses. Finally, I propose approaches
      for how to positively influence and drive the future of the global stem cell
      ecosystem.

PMID- 30289056
TI  - Who enrols in voluntary micro health insurance schemes in low-resource settings?
      Experience from a rural area in Bangladesh.
AB  - BACKGROUND: Micro health insurance (MHI) has proved to be a potential health
      financing tool for many developing countries. Bangladesh also included MHI in its
      current health-financing strategy which aims to achieve universal health
      coverage. However, low uptake, low renewal and high dropouts have historically
      challenged financial sustainability of these schemes. OBJECTIVE: This study aims
      to identify factors influencing people from low-resource settings, particularly
      those from Bangladesh, to enrol in MHI schemes. METHODS: The study analyses the
      'Amader Shasthya' MHI scheme operating in Chakaria, a sub-district under Cox's
      Bazar district, Bangladesh. A household survey was carried out during May-June
      2016 among 2,000 households from the scheme coverage area. The Outreville's
      insurance-demand framework was used to identify enrolment influencing factors.
      Multivariate logistic regression analysis was carried out to identify significant
      influencing factors of enrolment. RESULTS: Enrolment influencing factors were
      identified in four dimensions: economic, socio-cultural, demographic and
      structural. Households with the main income earner having 10+ years of schooling
      (odds 1.9 [CI 1.2-2.9] compared to illiterate), having financial literacy (odds
      1.5 [CI 1.2-1.8] compared to financially illiterate) and being a public/private
      service holder (odds 1.6 [CI 1.1-2.4] compared to menial labour) were more likely
      to enrol. Membership in development programmes of NGOs also influenced enrolment
      decision significantly (odds 1.3 [CI 1.0-1.5]). The presence of chronic illness
      in household encouraged enrolment (odds 1.5 [CI 1.2-1.8]). Households living
      closer to health centres were more likely to enrol (odds 2.1 [CI 1.6-2.7])
      compared to those living further away. CONCLUSION: The findings are expected to
      have significant implications in terms of designing similar health insurance
      schemes, particularly in terms of designing demand-driven and context adapted
      schemes that have greater potential to attract a larger client pool, ensure
      effective risk pooling and eventually expedite the achievement of universal
      health coverage in low-resource settings.

PMID- 30289054
TI  - Assessing the function of pneumococcal neuraminidases NanA, NanB and NanC in in
      vitro and in vivo lung infection models using monoclonal antibodies.
AB  - Streptococcus pneumoniae isolates express up to three neuraminidases
      (sialidases), NanA, NanB and NanC, all of which cleave the terminal sialic acid
      of glycan-structures that decorate host cell surfaces. Most research has focused
      on the role of NanA with limited investigations evaluating the roles of all three
      neuraminidases in host-pathogen interactions. We generated two highly potent
      monoclonal antibodies (mAbs), one that blocks the enzymatic activity of NanA and
      one cross-neutralizing NanB and NanC. Total neuraminidase activity of clinical S.
      pneumoniae isolates could be inhibited by this mAb combination in enzymatic
      assays. To detect desialylation of cell surfaces by pneumococcal neuraminidases,
      primary human tracheal/bronchial mucocilial epithelial tissues were infected with
      S. pneumoniae and stained with peanut lectin. Simultaneous targeting of the
      neuraminidases was required to prevent desialylation, suggesting that inhibition
      of NanA alone is not sufficient to preserve terminal lung glycans. Importantly,
      we also found that all three neuraminidases increased the interaction of S.
      pneumoniae with human airway epithelial cells. Lectin-staining of lung tissues of
      mice pre-treated with mAbs before intranasal challenge with S. pneumoniae
      confirmed that both anti-NanA and anti-NanBC mAbs were required to effectively
      block desialylation of the respiratory epithelium in vivo. Despite this, no
      effect on survival, reduction in pulmonary bacterial load, or significant changes
      in cytokine responses were observed. This suggests that neuraminidases have no
      pivotal role in this murine pneumonia model that is induced by high bacterial
      challenge inocula and does not progress from colonization as it happens in the
      human host.

PMID- 30289058
TI  - Source flexibility in schizophrenia: specificity and role in auditory
      hallucinations.
AB  - INTRODUCTION: One important aspect of human cognition relies on the ability to
      bias attention towards stimulus-independent and stimulus-oriented thoughts and to
      switch between these states - or source flexibility. This mechanism has received
      very little attention in the literature, and in particular in schizophrenia.
      Moreover, there is good reason to believe that this mechanism could also be
      implicated in hallucinations, but this hypothesis has never been examined. Thus,
      the aim of the present study was, for the first time in the literature, to
      explore source flexibility abilities in schizophrenia and their potential
      relations with auditory hallucinations. METHODS: Forty persons diagnosed with
      schizophrenia and 26 healthy controls were evaluated with tasks assessing source
      flexibility, cognitive flexibility and processing speed. Patients were also
      assessed with a measure of hallucinations and delusions. RESULTS: Results
      revealed that persons diagnosed with schizophrenia presented a poorer performance
      than healthy controls for source flexibility. Moreover, results demonstrated that
      source flexibility performance could not be explained by a more general
      impairment of processing speed or buy difficulties in cognitive flexibility.
      Finally, source flexibility was found to be related to hallucinations.
      CONCLUSIONS: Source flexibility plays an important role in schizophrenia and in
      particular is a cognitive mechanism involved in hallucinations.

PMID- 30289057
TI  - Application of PLGA/FGF-2 coaxial microfibers in spinal cord tissue engineering:
      an in vitro and in vivo investigation.
AB  - AIM: Scaffolds are a promising approach for spinal cord injury (SCI) treatment.
      FGF-2 is involved in tissue repair but is easily degradable and presents
      collateral effects in systemic administration. In order to address the stability
      issue and avoid the systemic effects, FGF-2 was encapsulated into core-shell
      microfibers by coaxial electrospinning and its in vitro and in vivo potential
      were studied. Materials & methods: The fibers were characterized by
      physicochemical and biological parameters. The scaffolds were implanted in a
      hemisection SCI rat model. Locomotor test was performed weekly for 6 weeks. After
      this time, histological analyses were performed and expression of nestin and GFAP
      was quantified by flow cytometry. Results: Electrospinning resulted in uniform
      microfibers with a core-shell structure, with a sustained liberation of FGF-2
      from the fibers. The fibers supported PC12 cells adhesion and proliferation.
      Implanted scaffolds into SCI promoted locomotor recovery at 28 days after injury
      and reduced GFAP expression. CONCLUSION: These results indicate the potential of
      these microfibers in SCI tissue engineering. [Formula: see text].

PMID- 30289060
TI  - Efficient expression and purification of Cryptochrome1 from Columbia livia in E.
      coli.
AB  - Cryptochrome is a flavin-binding blue-light photoreceptor that functions in
      growth and development in plants, the circadian clock in animals and navigation
      in birds. However, a lack of purified cryptochrome has hindered studies of the
      structure and function of this protein. In this study, we obtained a substantial
      amount of the Columbia livia Cryptochrome1 (ClCry1) protein by using a
      prokaryotic expression system. In addition, we performed comprehensive
      experiments to assess the influence of several factors on the purification and
      yield of ClCry1, such as the inducer that was used, temperature, duration of
      expression and type of growth medium. These assays clearly indicated that such
      factors influenced the purification and yield of ClCry1. Moreover, flavin adenine
      dinucleotide (FAD) was added during expression and purification of ClCry1, which
      resulted in production of large amounts of ClCry1 protein with the FAD cofactor
      from the Escherichia coli (E. coli) heterologous expression system. We believe
      that this study provides a novel avenue to acquire large amounts of ClCry1 that
      contains FAD and lays the foundation for studies of the geomagnetic navigation
      mechanism of Aves.

PMID- 30289061
TI  - BaltPLA2: a new phospholipase A2 from Bothrops alternatus snake venom with
      antiplatelet aggregation activity.
AB  - In last decades, snake venoms have aroused great interest of the medicine due to
      the pathophysiological effects caused by their toxins. These include the
      phospholipases A2, low molecular weight proteins capable of causing haemorrhagic,
      myotoxic, inflammatory and neurotoxic effects after an ophidian accident. The
      present work describes the isolation and biochemical characterization of a new
      PLA2 isolated from the B. alternatus snake venom, which was named BaltPLA2. The
      rapid and efficient purification of this toxin was performed using only two
      chromatography steps (anion exchange and hydrophobic chromatography). BaltPLA2 is
      an acidic protein (pI 4.4) with an apparent molecular mass of 17000 (SDS-PAGE)
      and 14074.74 Da (MALDI TOF/TOF). Analysis of fragments ion by MS / MS showed the
      following internal amino acid sequence SGVIICGEGTPCEK, which did not exhibit
      homology with other PLA2 from the same venom. BaltPLA2 is a catalytically active,
      which displayed an anticoagulant action, inhibition of platelet aggregation
      induced by epinephrine (~ 80%) and ADP (24%). BaltPLA2 also was able to induce
      myonecrosis and the release of cytokines (IL-10, IL-12 and TNF-alpha) in
      macrophages culture. The results presented in this work greatly contribute to a
      better understanding of the mechanism of enzymatic and pharmacological actions of
      PLA2s from snake venoms and they may contribute to its application in medical
      research.

PMID- 30289062
TI  - QRPR and HCQRPQ, two peptides from soybean, have an inhibitory effect on the
      proliferation of HepG2 cells.
AB  - In this study, we investigated the possible inhibitory effect of soy peptides
      QRPR and HCQRPQ on human liver cancer cells (HepG2) and their underlying
      mechanisms. An MTS assay showed that QRPR used in combination with HCQRPQ had a
      significant inhibitory effect on the proliferation of HepG2 cells compared to the
      effect of QRPR or HCQRPQ alone, and the cytotoxicity was low. An Annexin V/PI
      assay revealed that QRPR used in combination with HCQRPQ induced apoptosis in
      HepG2 cells; this outcome was also confirmed by the increased expression of
      caspase-3. The ultrastructural changes of cells induced by soybean peptides were
      observed via transmission microscopy. In addition, the combination of QRPR and
      HCQRPQ had a significant effect on the cell cycle of HepG2 cells compared with
      the effect of the control group. Using the real-time quantitative reverse
      transcriptase-polymerase chain reaction method, the mRNA expression levels of
      caspase-8 were significantly increased by QRPR used in combination with HCQRPQ (P
      < 0.001). Western blot results showed that QRPR used in combination with HCQRPQ
      increased the expression of caspase-8 and caspase-3 in a dose- and time-dependent
      manner. ELISA showed that the combination of QRPR and HCQRPQ reduced the
      secretion of TNF-alpha. We speculated that QRPR used in combination with HCQRPQ
      exerts its inhibitory effect possibly through the TNF-alpha mediated pathway.
      Taken together, all results suggested the promising chemotherapeutic potential of
      QRPR and HCQRPQ for the treatment of hepatocellular carcinoma.

PMID- 30289063
TI  - Structural Insights on the Obscurin-Binding Domains in Titin.
AB  - INTRODUCTION: The giant muscular proteins titin and obscurin bind to each other
      at the Z-disk during muscle development. This binding event is mediated through
      two domains from each protein: ZIg9/10 from titin and Ig58/59 from obscurin. This
      interaction helps stabilize and organize the sarcomere; ablation of this binding
      leads to muscular dystrophy. OBJECTIVE: Here we solve the high-resolution
      solution structure of titin ZIg10 and further delineate which sections of titin
      bind to obscurin. MATERIALS AND METHODS: Solution NMR, Circular Dichroism, and
      SEC-MALS were used to biophysically characterize the titin domains involved in
      this titin-obscurin interaction. RESULTS AND CONCLUSION: We present the high
      resolution solution structure of titin ZIg10. Additionally, we show that titin
      ZIg9 drives the titin-obscurin interaction, while ZIg10 does not actively
      participate in the titin-obscurin interaction but instead acts to stabilize ZIg9.

PMID- 30289064
TI  - Neuroprotective effects of extracts from the radix Curcuma aromatic on H2O2
      induced damage in PC12 cells.
AB  - : Aim & objectives: Curcumins, also known as diarylheptanoids, are regarded as
      characteristic constituents in Curcuma, which have obviously neuroprotective
      activities against oxidative stress. As one of Traditional Chinese Medicines from
      Curcuma, the radix of Curcuma aromatic is also rich in curcumins, but its
      neuroprotective activity and underlying mechanism remains unknown. The aim of
      current study is to evaluate the neuroprotective effects of different extracts
      from the radix of C. aromatic (ECAs) on hydrogen peroxide (H2O2) -damaged PC12
      cells. MATERIAL AND METHODS: The model of oxidative stress damage was established
      by treatment of 400 uM hydrogen peroxide (H2O2) on PC12 to induce cell damage.
      After the treatment of ECWs for 24 h, the cell viability, the release rate of
      lactate dehydrogenase (LDH), and the activities of superoxide dismutase (SOD),
      catalase (CAT) and glutathione (GSH) were measured to evaluate the
      neuroprotection of ECAs on that model. The possibly protecting mechanism of
      oxidative damage by measurement of level of ROS, cell apoptosis rate,
      mitochondrial membrane potential (MMP), morphologic change, the intracellular
      Ca2+ content (F340/F380) and the expressions of Bcl-2, Bax and Caspase-3.
      Additionally, the constituents from those extracts were analyzed by HPLC-DAD-Q
      TOF-MS method. RESULTS: Compared with a positive control, Vitamin E, 10 ug/ml of
      95 % EtOH extract (HCECA) and 75 % EtOH extract (MCECA) can markedly increase the
      rate of cell survival and enhance the antioxidant enzyme activities of SOD, CAT,
      increase the levels of GSH, decrease LDH release and the level of ROS, attenuate
      the intracellular Ca2+ overloading, reduce the cell apoptotic rate and stabilize
      MMP, down-regulate Bcl-2 expression, up-regulate Bax and caspase-3 expression,
      improve the change of cell morphology. The chemical analysis showed
      diarylheptanoids and sesquiterpenoids are the major chemicals in those extracts
      and the former was richer in HCECA and MCECA than others. CONCLUSIONS: These
      findings indicated that the effects of HCECA and MCECA on inhibiting the cells
      damage induced by H2O2 in PC12 are better than other extracts from the radix of
      C. aromatic through the mechanisms of apoptosis inhibition in PC12, and the
      active constituents with neuroprotective effects consisting in those two extracts
      are diarylheptanoids.

PMID- 30289065
TI  - Graphene and Graphene Oxide Applications for SERS Sensing and Imaging.
AB  - Surface Enhanced Raman Spectroscopy (SERS) has long history as ultrasensitive
      platform for the detection of biological species from small aromatic molecules to
      complex biological systems as circulating tumor cells. Thanks to unique
      properties of graphene, the range of SERS applications has largely expanded.
      Graphene is efficient fluorescence quencher improving quality of Raman spectra.
      It contributes also to the SERS enhancement factor through the chemical
      mechanism. In turn, the chemical flexibility of reduced graphene oxide (RGO)
      enables tunable adsorption of molecules or cells on SERS active surfaces.
      Graphene oxide composites with SERS active nanoparticles have been also applied
      for Raman imaging of cells. This review presents a survey of SERS assays
      employing graphene or RGO emphasizing the improvement of SERS enhancement brought
      by graphene or RGO. The structure and physical properties of graphene and RGO
      will be discussed too.

PMID- 30289066
TI  - Advances in gene therapy for erectile dysfunction: promises and challenges.
AB  - Erectile dysfunction (ED) is a major health problem in men. Over the past few
      decades, oral phosphodiesterase type 5 (PDE5) inhibitors have been adopted as the
      recommended strategy to treat ED in the majority of cases. However, these oral
      medications require on-demand access and are not effective in some hard-to-treat
      populations. Other alternative treatments are also not satisfactory. In recent
      years, a novel therapeutic approach against ED, gene therapy, has shown great
      potential in preclinical models designed to provide long-term improvement of
      erectile function and the underlying conditions. Gene therapy refers to the use
      of viral and non-viral vectors to deliver therapeutic genes to tissues via direct
      or transduced cell-mediated approaches. With the growing knowledge of the
      molecular mechanisms involved in the pathophysiology of ED, a number of
      therapeutic gene strategies have been extensively tested and proven to be
      effective in many animal models. However, only few of them have been evaluated in
      clinical trials. Safety concerns are the major obstacles to be addressed before
      clinical application can be considered. In this review, we summarize the
      advancements in gene therapy for ED treatment, with an emphasis on the emerging
      stem cell-based approaches, as well as other combinational strategies. The
      challenges facing its future application for ED treatment are also discussed.

PMID- 30289067
TI  - Bone Minimodeling, a Special Modeling Pattern and Potential as Therapeutic Target
      for Osteoporosis.
AB  - The concept of minimodeling is defined as a kind of focal bone formation that
      features the absence of preceding bone absorption by osteoclasts. In the process
      of minimodeling, osteogenetic and osteoclastic activities are decoupled. Linear
      boundary between old bone and new bone can be discovered. Frost et al. presumed
      that minimodeling in trabeculae can continue throughout life. The concept of
      minimodeling is not new, however its function and nature are still imperfectly
      understood. Our review will focus on minimodeling-based formation in 5 aspects
      below: 1. compare the minimodeling with remodeling regarding 10 items; 2.
      describe the histological observation to characterize remodeling and minimodeling
      formation sites; 3. present evidence of bone anabolic agents which start bone
      minimodeling; 4. discuss the mechanism and target cells involved in bone
      minimodeling; 5. interpretate the increased osteogenic potential and trabecular
      connectivity with minimodeling-based formation; 6. Depict modeling patterns of
      the bone implant interface and peri-implant osteogenesis in osteoporosis. This
      review provides an in-depth knowledge regarding minimodeling comprehensively and
      its potential contributions in skeletal homeostasis and application prospect in
      improving the success rate of dental implant in osteoporosis.

PMID- 30289068
TI  - Co-Existence of Novel PDE6A Mutations and A Recurrent RPGR Mutation: A Potential
      Explanation for Phenotypic Diversity in Female RPGR Mutation Carriers.
AB  - BACKGROUND: To report the co-existence of novel biallelic PDE6A mutations and
      heterozygous RPGR mutation in a Chinese female patient with retinitis pigmentosa
      (RP), and to analyze the intrafamilial phenotypic diversity. METHODS: Three
      patients with retinopathy and four healthy family members were included in
      genetic and clinical analyses. Personal medical records were obtained from
      another four unaffected female family members who refused blood donation. Family
      history was carefully recorded. Each patient received comprehensive ophthalmic
      tests. Targeted next-generation sequencing (NGS) approach was performed on the
      proband to determine the retinopathy causative mutation for this family. In
      silico analysis was also applied to analyze the pathogenesis of identified
      mutations. RESULTS: The two recruited male patients were diagnosed with RP, and
      the female patient RP sine pigmento (RPSP). Genetic assessments revealed a
      recurrent RPGR mutation, c.1926_1927insA, carried by all three patients and
      segregated the disease status. Three other unaffected female family members were
      confirmed as carriers for the identified RPGR mutation, and another four as
      obligate carriers. Interestingly, of all the eight female RPGR mutation carriers
      in this family, only one female developed retinal dystrophy. Comprehensive
      genetic analysis of this patient unraveled additional biallelic PDE6A mutations,
      c.[1066-9delT];[2324delG], carried solely by this individual. CONCLUSIONS: Taken
      together, we hypothesize that the phenotypic variability presented by female RPGR
      mutation carriers may be attributed to the co-existence of other disease
      causative mutations. Our study also emphasizes the importance of comprehensive
      genetic analysis in these female carriers, which will contribute to better
      diagnosis, prognosis, and treatment for these patients.

PMID- 30289069
TI  - Coding and Non-coding: Molecular Portrait of GIST and its Clinical Implication.
AB  - Gastrointestinal stromal tumours are the most common mesenchymal tumours of the
      gastrointestinal tract. Despite similar mutation pattern of activating mutations
      in KIT or PDGFRA receptors in 85% of cases, they demonstrate significantly
      heterogeneous clinical behaviour and pathological characteristics. This
      heterogeneity opens the question of the role of other factors and mechanisms of
      regulation in the development of GIST. Additional mutations in downstream
      effectors of GIST related signalling pathways or aberrant expression of non
      coding RNAs may be additional contributing factors, the latter being increasingly
      recognized in carcinogenesis in general. Recently, a substantial progress has
      been achieved in understanding the functional roles of lncRNAs in GIST suggesting
      their potential employment as biomarkers and therapeutic targets in GIST.
      Moreover, some miRNAs have recently been found to be able to sensitize cells to
      imatinib, which could be an attractive option to overcome the resistance to the
      drug, which hampers the efficacy of GIST treatment. Therefore, the advantage can
      be taken of both coding and non-coding parts of the genome in order to
      significantly improve prognostication and help find personalized therapy for
      patients, depending on a subtype of GIST and personal characteristics.

PMID- 30289070
TI  - Genetic Modifiers of Fetal Haemoglobin (HbF) and Phenotypic Severity in beta
      Thalassemia Patients.
AB  - BACKGROUND: The phenotypic severity of beta-thalassemia is highly modulated by
      three genetic modifiers: beta-globin (HBB) mutations, co-inheritance of alpha
      thalassemia and polymorphisms in the genes associated with fetal haemoglobin
      (HbF) production. This study was aimed to evaluate the effect of HbF related
      polymorphisms mainly in the HBB cluster, BCL11A (B-cell CLL/lymphoma 11A) and
      HBS1L-MYB (HBS1-like translational GTPase-MYB protooncogene, transcription
      factor) with regards to clinical severity. METHODS: A total of 149 patients were
      included in the study. HBA and HBB mutations were characterised using multiplex
      PCR, Sanger sequencing and multiplex ligationdependent probe amplification. In
      addition, 35 HbF polymorphisms were genotyped using mass spectrometry and PCR
      restriction fragment length polymorphism (PCRRFLP). The genotype-phenotype
      association was analysed using SPSS version 22. RESULTS: Twenty-one HBB mutations
      were identified in the study population. Patients with HBB mutations had
      heterogeneous phenotypic severity due to the presence of other secondary
      modifiers. Co-inheritance of alpha-thalassemia (n = 12) alleviated disease
      severity of beta-thalassemia. In addition, three polymorphisms (HBS1LMYB,
      rs4895441 [P = 0.008, odds ratio (OR) = 0.38 (0.18, 0.78)], rs9376092 [P = 0.030,
      OR = 0.36 (0.14, 0.90)]; and olfactory receptor [OR51B2] rs6578605 [P = 0.018, OR
      = 0.52 (0.31, 0.89)]) were associated with phenotypic severity. Secondary
      analysis of the association between single-nucleotide polymorphisms with HbF
      levels revealed three nominally significant SNPs: rs6934903, rs9376095 and
      rs9494149 in HBS1L-MYB. CONCLUSION: This study revealed 3 types of HbF
      polymorphisms that play an important role in ameliorating disease severity of
      beta-thalassemia patients which may be useful as a predictive marker in clinical
      management.

PMID- 30289071
TI  - MiR-19b Functions as a Potential Protector in Experimental Autoimmune
      Encephalomyelitis.
AB  - BACKGROUND: MicroRNA-19b (miR-19b) is essential in determining oligodendroglia
      proliferation. Phosphatase and tensin homologue on chromosome 10 (PTEN) is
      considered the target of miR-19b and participates in oligodendrocyte
      differentiation and proliferation. METHODS: Murine EAE was induced by myelin
      oligodendrocyte glycoprotein (MOG35- 55). For EAE reversal, artificially
      synthesized agomiR-19b was intravenous injected after immunization. RESULTS: We
      found that the expression of miR-19b is significantly reduced in an experimental
      autoimmune encephalomyelitis (EAE) mouse model. This downregulation, which is
      associated with the neurological scores, can be dramatically ameliorated by
      agomiR-19b. Our results show that agomiR-19b increases the expression of myelin
      basic protein (MBP) and cyclic nucleotide phosphodiesterase (CNP), which are
      regularly utilized as molecular markers of oligodendrocytes. Furthermore, our
      study also revealed that miR-19b probably affects the expression of PTEN in the
      EAE model. CONCLUSION: These results indicate that the restoration of miR-19b
      probably exerts its therapeutic effect by affecting PTEN in the pathogenesis of
      EAE.

PMID- 30289072
TI  - Probable Mechanisms Involved in Immunotoxin Mediated Capillary Leak Syndrome
      (CLS) and Recently Developed Countering Strategies.
AB  - Antibody-toxin fused agents or immunotoxins, are a newly engineered class of
      cytotoxic agents consisting of a bacterial or plant toxin moiety hooked up either
      to a monoclonal antibody or a specific growth factor. Nevertheless, acquiring a
      full potency in clinic is mostly restricted due to the Capillary leak syndrome
      (CLS), a serious immune provoked, life-threatening side effect, subsequent to the
      endothelial damage, resulting in fluid escape from the bloodstream into tissues
      including lungs, muscle and brain, developing organ failure and eventually death.
      Proposed underlying mechanisms include direct damage to endothelial cells, acute
      inflammation, Lymphokine-activated killer (LAK) cells engagement, alteration in
      cell-cell/cell-matrix connectivities and cytoskeletal dysfunction. Very poor
      biodistribution and heterogeneous extravasation pattern in tumor site result in
      accumulation of ITs close to the extravasation site, gradual toxin release and
      initiation of nearby endothelial cells lysis, secretion of pro-inflammatory
      cytokines, development of acute inflammation and engagement of Lymphokine
      activated killer (LAK) cells. Intrinsic immunogenicity of applied toxin moiety is
      another important determinant of CLS incidence. Toxins with more intrinsic
      immunogenicity possess more probability for CLS development. Recently,
      development of new generations of antibodies and mutated toxins with conserved
      cytotoxicity has partly tapered risk of CLS development. Here, we describe
      probable mechanisms involved in CLS and introduce some of the recently applied
      strategies for lessening incidence of CLS as much as possible.

PMID- 30289073
TI  - VEGFR2 and VEGF-C Suppresses the Epithelial-Mesenchymal Transition Via YAP in
      Retinal Pigment Epithelial Cells.
AB  - BACKGROUND: Whereas retinal pigment epithelial (RPE) cells are known to secrete
      VEGF-A and VEGFR2, the functions of the autocrine VEGF signaling remain unclear.
      Meanwhile, anti-VEGF therapies have been applied routinely to treat ocular
      vascular diseases. OBJECTIVE: The aim of this study was to determine the
      functions of the VEGF signaling in RPE cells and evaluate the consequences of its
      interruption. METHODS: The genes involved in the VEGF and Hippo signal pathways
      were knocked down with siRNAs in both ARPE-19 cell line and human primary RPE
      cells via transient transfection whereas overexpression of VEGFR2 was mediated
      via adenovirus transduction. Expression of the epithelial-mesenchymal transition
      (EMT) markers and the downstream genes of YAP were determined by real-time PCR
      and Western Blot analysis. Immunofluorescence staining was utilized to determine
      gene expression in tissue and mouse samples. RESULTS: Knockdown of VEGFR2 results
      in epithelial-mesenchymal transition in vitro and in vivo. Overexpression of
      VEGFR2 suppresses TGF beta-mediated EMT in RPE cells. Loss of VEGF-C rather than
      VEGF-A induces EMT. Mechanistically, the VEGFR2 ablation-induced EMT in RPE cells
      is mediated by activation of YAP, an effector of the Hippo pathway. Finally, the
      immunohistochemical analysis of VEGFR2 and YAP in human proliferative
      vitreoretinopathy (PVR) membranes indicates a tendency of an inverse correlation
      between VEGFR2-positive and YAP-positive cells. CONCLUSIONS: Our results disclose
      unexpected novel roles of VEGFR2 and VEGF-C in the process of EMT of RPE cells
      and in the Hippo pathway. The data shown here demonstrated that VEGFR2 and VEGF-C
      are important to maintain the normal physiological state of RPE cells.

PMID- 30289074
TI  - Nose to Brain Delivery of Galantamine Loaded Nanoparticles: In-vivo
      Pharmacodynamic and Biochemical Study in Mice.
AB  - BACKGROUND: Presence of blood brain barrier is one of the major hurdle in drug
      delivery to brain for the treatment of neurological diseases. Alternative and
      more effective drug delivery approaches have been investigated for the drug
      targeting to brain in therapeutic range. OBJECTIVE: The present investigation was
      carried out to improve the galantamine bioavailability in brain by intranasal
      drug delivery through thiolated chitosan nanoparticles and compared to nasal and
      oral delivery of its solution using pharmacodynamic activity as well as
      biochemical estimation. METHODS: Thiolated chitosan (modified) nanoparticles were
      fabricated using modified ionic gelation method and intranasal delivery is
      evaluated by reversal of scopolamine induced amnesia and biochemical estimation
      of acetylcholinesterase activity in Swiss albino mice brain. Scopolamine (0.4
      mg/kg, i.p.) was used to induce amnesia. Piracetam (400mg/kg, i.p.) was used as
      positive control. Mice were treated with galantamine solution (4mg/kg) by oral
      and nasal route and formulated galantamine nanoparticles (equivalent to 4mg/kg)
      by intranasal administration for 7 successive days and the results were compared
      statistically. RESULTS: Intranasal delivery of galantamine loaded thiolated
      chitosan nanoparticles was found significant (p<0.05) as compared to oral and
      nasal administration of its solution, by pharmacodynamic study and biochemical
      estimation of acetylcholinesterase activity in Swiss albino mice brain.
      CONCLUSION: Significant recovery in amnesia induced mice model by intranasal
      administration of galantamine loaded thiolated chitosan nanoparticles established
      the relevance of nose to brain delivery over the conventional oral therapies for
      the treatment of Alzheimer's disease.

PMID- 30289075
TI  - Asymmetric Changes in Limbic Cortex and Planum Temporale in Patients with
      Alzheimer Disease.
AB  - BACKGROUND: There are several cortical areas related to the limbic system that
      form the output from the hippocampal formation whose cellular and morphological
      features are important for the onset and progression of AD. We hypothesized that
      there would be a significant difference in the size of cortical pyramidal neurons
      and that there would also be a hemispheric asymmetry between Alzheimer disease
      patients and controls. These differences would potentially be accompanied by an
      increase in the numbers of Fluoro-Jade B-positive degenerating cortical neurons
      and a corresponding decrease in the numbers of DAPI-stained cortical neuronal
      nuclei in subjects with AD compared to controls. Such changes could potentially
      be used as another marker in postmortem neuropathological diagnosis of AD.
      METHODS: We measured absolute numbers of DAPI and Fluoro-Jade B stained cells in
      five cortical areas of the limbic system and four subareas of planum temporale in
      the post-mortem brains of subjects with Alzheimer disease. We also measured the
      size of pyramidal neurons in layer III in the five cortical areas of the limbic
      system in these subjects. All measurements were performed separately for the left
      and right hemisphere in order to identify asymmetries between the two
      hemispheres. RESULTS: We observed a significant decrease in numbers of DAPI
      stained cells in layers IV-VI of the anterior cingulate gyrus on the right side,
      in layers I-III of the posterior cingulate gyrus on the left side, in layers IV
      VI in the transition region from superior temporal gyrus into planum temporale on
      the right and in layers IV-VI in the transition from planum temporale to insular
      cortex on the left. We also observed a significant increase in the numbers of
      Fluoro-Jade stained cells in layers I-III of the anterior cingulate gyrus and in
      layers I-III on the left and layers IV-VI of the right gyrus of Heschl.
      Shortening of the size of layer III pyramidal neurons in subjects with
      Alzheimer's disease was found in the anterior cingulate gyrus on the right, in
      the posterior cingulate gyrus and entorhinal cortex on the left and on the right
      in the parahippocampal gyrus. CONCLUSION: Our study demonstrates asymmetries in
      different cortical regions of the temporal lobe that can be used as another
      marker in the postmortem diagnosis of AD.

PMID- 30289076
TI  - The Implications of Autophagy in Alzheimer's Disease.
AB  - The pathogenic mechanisms of Alzheimer's Disease (AD) involve the deposition of
      abnormally misfolded proteins, amyloid beta protein (Abeta) and tau protein.
      Abeta comprises senile plaques, and tau aggregates form Neurofibrillary Tangles
      (NFTs), both of which are hallmarks of AD. Autophagy is the main conserved
      pathway for the degeneration of aggregated proteins, Abeta, tau and dysfunctional
      organelles in the cell. Many animal model studies have demonstrated that
      autophagy normally functions as the protective factor against AD progression
      associated with intracytoplasmic toxic Abeta and tau aggregates. The upregulation
      of autophagy can also be favorable in AD treatment. An improved understanding of
      the signaling pathways that regulate autophagy is critical to developing AD
      treatments. The cellular and molecular machineries of autophagy, their function
      in the pathogenesis of AD, and current drug discovery strategies will be
      discussed in this review.

PMID- 30289077
TI  - The association of neuronal stress with activating transcription factor 3 in
      dorsal root ganglion of in vivo and in vitro models of bortezomib-induced
      neuropathy.
AB  - The notion that proteasome inhibitor bortezomib (BTZ) induced intracellular
      oxidative stress resulting in peripheral neuropathy has been generally accepted.
      The association of mitochondrial dysfunction, cell apoptosis, and endoplasmic
      reticulum (ER) stress with intracellular oxidative stress is ambiguous and still
      needs to be investigated. Here we report a mechanism underlying the action of BTZ
      induced intracellular oxidative stress, mitochondrial dysfunction, cell
      apoptosis, and ER stress via the activation of activating transcription factor 3
      (ATF3) in primary cultured dorsal root ganglion (DRG) neurons and in DRG from
      painful peripheral neuropathic rats. ATF3 is a stress-hub gene which was
      upregulated in DRG neurons after different kinds of peripheral nerve injuries. In
      the present study, BTZ administration caused the upregulation of ATF3 paralleled
      with intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis,
      and ER stress in DRG neurons both in vitro and in vivo. Blocking ATF3 signaling
      by small interfering RNA (siRNA) gene silencing technology resulted in decreased
      intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER
      stress in DRG neurons after BTZ treatment. This study exhibited important
      mechanistic insight into how BTZ induces neurotoxicity through the activation of
      ATF3 resulting in intracellular oxidative stress, mitochondrial dysfunction, cell
      apoptosis, and ER stress and provided a novel potential therapeutic target by
      blocking ATF3 signaling.

PMID- 30289078
TI  - Burden of Congenital Rubella Syndrome (CRS) in Bangladesh: Systematic review of
      existing literature and transmission modelling of sero-prevalence studies.
AB  - Background and objectives Congenital Rubella Syndrome (CRS) is the leading cause
      of vaccine preventable congenital anomalies. Comprehensive country-level data on
      the burden of CRS in low and middle-income countries, such as Bangladesh, are
      scarce. This information is essential for assessing the impact of rubella
      vaccination programs. We aim to systematically review literature on the
      epidemiology of CRS and estimate the burden of CRS in Bangladesh. Methods We
      conducted a systematic review of existing literature and transmission modelling
      of sero-prevalence studies to estimate the pre-vaccine period burden of CRS in
      Bangladesh. OVID Medline (1948 - 23 November 2016) and OVID EMBASE (1974 - 23
      November 2016) were searched using a combination of database specific controlled
      vocabulary and free text terms. We used an age-stratified deterministic model to
      estimate the pre-vaccination burden of CRS in Bangladesh. Findings Ten articles
      were identified, published between 2000 and 2014, including seven cross-sectional
      studies, two case series and one analytical case-control study. Rubella sero
      positivity ranged from 47.0% to 86.0% among all age population. Rubella sero
      positivity rose with age. Rubella sero-positivity among women of childbearing age
      was 81.0% overall. The estimated incidence of CRS was 0*99 per 1,000 live births,
      which corresponds to approximately 3,292 CRS cases annually in Bangladesh.
      Conclusion The estimated burden of CRS in Bangladesh during the pre-vaccination
      period was high. This will provide important baseline information to assess the
      impact and cost-effectiveness of routine rubella immunisation, introduced in 2012
      in Bangladesh.

PMID- 30289079
TI  - Epigenetics in neurodegenerative diseases: the role of histone deacetylases.
AB  - Imbalance in histone acetylation levels and consequently the dysfunction in
      transcription are associated with a wide variety of neurodegenerative diseases.
      Histone proteins acetylation and deacetylation is carried out by two opposite
      acting enzymes, histone acetyl-transferases and histone deacetylases (HDACs),
      respectively. In-vitro and in-vivo animal models of neurodegenerative diseases
      and post mortem brains of patients have been reported overexpressed level of
      HDACs. In recent past numerous studies have indicated that HDAC inhibitors
      (HDACIs) might be a promising class of therapeutic agents for treating these
      devastating diseases. HDACs being a part of repressive complexes, the outcome of
      their inhibition has been attributed to enhanced gene expression due to
      heightened histoneacetylation. Beneficial effects of HDACIs has been explored
      both in preclinical and clinical studies of these diseases. Thus, their screening
      as future therapeutics for neurodegenerative diseases has been widely explored.
      In this review, we focus on the putative role of HDACs in neurodegeneration and
      further discuss their potential as a new therapeutic avenue for treating
      neurodegenerative diseases.

PMID- 30289080
TI  - Cushing's Syndrome should be Cited as a Disease with High Cardiovascular Risk in
      Relevant Guidelines.
AB  - The intention of the paper is to give rationale and to suggest enlisting
      Cushing's syndrome (CS) amongst high cardiovascular (CV) risk conditions. A
      considerable amount of data refers to several-fold amplified mortality in CS. The
      causes are based on high occurrence of many CV risk factors in persons with CS
      (e.g., adiposity, arterial hypertension, dyslipidemia, as well as diabetes
      mellitus /DM/). Therefore, practically all individuals with CS have
      correspondingly the metabolic syndrome (MetSy), which is known as laden with high
      CV risk. Characteristically, in spite of the young average age, numerous of CS
      individuals dysplay a 'high' or a 'very high' CV risk, with the risk of a major
      CV event of over 20% in the following ten years. Although DM is listed as a
      condition with high cardiovascular risk CS is not, despite the fact that the
      greater part of CS population have either diabetes mellitus or diagnosed impaired
      glucose tolerance. CS is stated as a risk factor for aortic dissection in current
      guidelines, and it should be named as a disease with high CV risk (alike DM and
      chronic kidney disease) in the relevant guidelines, as well.

PMID- 30289082
TI  - Evaluation of salivary alkaline phosphatase and albumin in HIV infected patients:
      A historical cohort study
AB  - BACKGROUND: Saliva is very important complex biological oral fluid .Antioxidants
      are present in all body fluids. Uric acid, albumin, vitamins are some of non
      enzymatic molecular antioxidants.Alkaline phosphatase is related to cell injury
      and death. Objective: The aim of this study was evaluation of salivary alkaline
      phosphatase and albumin in HIV positive patients. METHODS: Case group were, 49
      HIV positive subjects,compared with 49 healthy control group. Oral clinical
      examination was carried out . Five ml unstimulated whole saliva was collected
      during 5 min with Navazesh method. Alkaline phosphatase was determined with
      spectrophotometric assay. Albumin was assessed by the nephelometric method.
      RESULTS: The results of this study showed significantly lower salivary albumin in
      case group in comparison to healthy control group (p= 0.001).HIV positive group
      had grater alkaline phosphatase than healthy control group. But this difference
      was not statistically significant (p=0.458). CONCLUSION: Salivary albumin level
      was significantly decreased and salivary alkaline phosphatase level slightly
      increased in HIV positive patients in comparison to healthy control group. All of
      HIV infected patient were in early phase of HIV infection with normal immune
      status. It could be estimated more salivary changes in late phase and AIDS step.

PMID- 30289081
TI  - The Gulf Familial Hypercholesterolemia Registry (Gulf FH): Design, Rationale and
      Preliminary Results.
AB  - AIM: To determine the prevalence, genetic characteristics, current management and
      outcomes of familial hypercholesterolaemia (FH) in the Gulf region. METHOD: Adult
      (18-70 years) FH patients were recruited from 9 hospitals and centres across 5
      Arabian Gulf countries. The study was divided into 4 phases and included patients
      from 3 different categories. In Phase 1, suspected FH patients (category 1) were
      collected according to the lipid profile and clinical data obtained through
      hospital record systems. In phase 2, patients from category 2 (patients with
      previous clinical diagnosis of FH) and category 1 were stratified into
      definitive, probable and possible FH according to the Dutch Lipid Clinic Network
      criteria. In phase 3, 500 patients with definitive and probable FH from
      categories 1 and 2 will undergo genetic testing for 4 common FH genes. In phase
      4, these 500 patients with another 100 patients from category 3 (patients with
      previous genetic diagnosis of FH) will be followed for 1 year to evaluate
      clinical management and cardiovascular outcomes. The Gulf FH cohort was screened
      from a total of 34,366 patients attending out-patient clinics. RESULTS: The final
      Gulf FH cohort consisted of 3,317 patients (mean age: 47+/-12 years, 54%
      females). The number of patients with definitive FH is 203. In this initial phase
      of the study, the prevalence of (probable and definite) FH is 1/232. CONCLUSIONS:
      The prevalence of FH in the adult population of the Arabian Gulf region is high.
      The Gulf FH registry, a first-of-a-kind multi-national study in the Middle East
      region, will help in improving underdiagnosis and undertreatment of FH in the
      region.

PMID- 30289084
TI  - Mentha pulegium aqueous extract exhibits antidiabetic and hepatoprotective
      affects in streptozotocin-induced diabetic rats.
AB  - OBJECTIVE: The aim of this work was to evaluate the antihyperglycemic activity of
      aerial parts aqueous extract (A.P.A.E) of Mentha pulegium (M. pulegium) on blood
      glucose levels in normal and streptozotocin(STZ)-induced diabetic rat. Also the
      glucose tolerance was evaluated in normal rats. Moreover, the histological
      sections and morphometric analysis at the liver and pancreas have been carried
      out in this investigation both in normal and STZ-diabetic rats. METHODS: The
      effect of A.P.A.E of M. pulegium (20 mg/kg) on blood glucose levels was
      investigated in normal and diabetic rats (n=6). Histopathological changes in
      liver and pancreas were examined under phase contrast microscope and a
      preliminary screening for various bioactive constituents was realized according
      to standard methods. KEY FINDINGS: Both single and repeated oral administration
      of A.P.A.E (20 mg/kg) caused a significant reduction on blood glucose levels in
      STZ-diabetic rats (p<0.0001). The morphometric analysis and histological sections
      realized in pancreas and liver have showed the beneficial effect of the A.P.A.E
      in cellular population. According to oral glucose tolerance test (OGTT), the
      aqueous extract has revealed an improvement of glucose tolerance in normal rat.
      Furthermore the preliminary phytochemical screening of A.P.A.E of M. pulegium has
      demonstrated the presence of various metabolite compounds including polyphenols,
      flavonoids, terpenoids tannins, cyanidins, sesquiterpenes, and glycosides.
      CONCLUSION: we conclude that the A.P.A.E of M. pulegium (20 mg/kg) exhibits a
      potent antihyperglycemic activity in STZ diabetic rats.

PMID- 30289083
TI  - Extra-thoracic Extrinsic Compression: An Unusual Cause of Dysphagia.
AB  - BACKGROUND: Dysphagia affects one in twenty-five adults yearly in the United
      States. OBJECTIVE: While dysphagia may be common, the prevalence of dysphagia may
      be underestimated primarily due to under-reporting. Dysphagia may be caused by
      intraluminal, intrinsic, extrinsic, or motility disorders. METHOD/RESULTS: We
      present a case of dysphagia caused by extra-thoracic extrinsic compression due to
      bra use. CONCLUSION: Despite many published reports on dysphagia caused by other
      diagnoses, we occasionally overlook extrinsic abdominal compression as the
      culprit for dysphagia.

PMID- 30289085
TI  - Potential impact of microRNA-423 gene variability in coronary artery disease.
AB  - AIM: Studies have evaluated the association of miRNA-423 C>A genotyping with the
      susceptibility to coronary artery disease but the results were contradictory.
      However, no studies have reported the association between miRNA-423 rs6505162 C>A
      polymorphism and susceptibility of coronary artery disease. MicroRNAs regulate
      expression of multiple genes involved in atherogenesis. Therefore, we
      investigated the association of microRNA-423C>T gene variations with
      susceptibility to coronary artery disease. METHODOLOGY: This study was conducted
      on 100 coronary artery disease patients and 117 matched healthy controls. The
      ggenotyping of the microRNA-423 rs6505162C>A was performed by using Amplification
      refractory mutation system PCR method (ARMS-PCR). RESULTS: A significant
      difference was observed in the genotype distribution among the coronary artery
      disease cases and sex-matched healthy controls (p=0.042). The frequencies of all
      three genotypes CC, CA, AA reported in the patient's samples were 38%, 56% and
      23% and in the healthy controls samples were 64%,48% and 4% respectively. Our
      findings showed that the microRNA-423 C>A variant was associated with an
      increased risk of coronary artery disease in codominant model (OR = 1.96, 95 %
      CI, 1.12-3.42; RR 1.35(1.05-1.75, p=0.017) of microRNA-423CA genotype and
      significant association in dominant model (OR 1.97(1.14.14-3.39), p=0.014) (CA+AA
      vs CC) and non-significant association for recessive model (OR=1.42, 95%CI=0.42
      4.83, P=0.56, AA vs CC+CA).While, the A allele significantly increased the risk
      of coronary artery disease (OR =1,56, 95 % CI, 1.03-2.37; p=0.035) compared to C
      allele. Therefore, it was observed that more than 1.96, 1.97 and 1.56 fold
      increased risk of developing coronary artery disease. CONCLUSION: Our findings
      indicated that microRNA-423 CA genotype and A allele are associated with an
      increased susceptibility to Coronary artery disease.

PMID- 30289087
TI  - Verb-based prediction during language processing: the case of Dutch and Turkish.
AB  - This study investigated whether cross-linguistic differences affect semantic
      prediction. We assessed this by looking at two languages, Dutch and Turkish, that
      differ in word order and thus vary in how words come together to create sentence
      meaning. In an eye-tracking task, Dutch and Turkish four-year-olds (N = 40), five
      year-olds (N = 58), and adults (N = 40) were presented with a visual display
      containing two familiar objects (e.g., a cake and a tree). Participants heard
      semantically constraining (e.g., "The boy eats the big cake") or neutral
      sentences (e.g., "The boy sees the big cake") in their native language. The Dutch
      data revealed a prediction effect for children and adults; however, it was larger
      for the adults. The Turkish data revealed no prediction effect for the children
      but only for the adults. These findings reveal that experience with word order
      structures and/or automatization of language processing routines may lead to
      timecourse differences in semantic prediction.

PMID- 30289086
TI  - The Effects of D-aspartate in Neurosteroids, Neurosteroid Receptors, and
      Inflammatory Mediators in Experimental Autoimmune Encephalomyelitis.
AB  - OBJECTIVE: Experimental autoimmune encephalomyelitis (EAE) is a widely used model
      for multiple sclerosis. The present study has been designed to compare the
      efficiencies of oral and intraperitoneal (IP) administration of D-aspartate (D
      Asp) on the onset and severity of EAE, the production of neurosteroids, and the
      expression of neurosteroid receptors and inflammatory mediators in brain of EAE
      mice. METHODS: In this study, EAE was induced in C57BL/6 mice treated with D-Asp
      orally (D-Asp-Oral) or by IP injection (D-Asp-IP). On the 20th day, brains
      (cerebrums) and cerebellums of mice were evaluated by histological analyses. The
      brains of mice were analyzed for: 1) Neurosteroid (Progesterone, Testosterone,
      17beta-estradiol) concentrations; 2) gene expressions of cytokines and
      neurosteroid receptors by reverse transcription polymerase chain reaction, and 3)
      quantitative determination of D-Asp using liquid chromatography-tandem mass
      spectrometry. Further, some inflammatory cytokines and matrix metalloproteinase-2
      (MMP-2) were identified in the mouse serum using enzyme-linked immunosorbent
      assay kits. RESULTS: Our findings demonstrated that after D-Asp was administered,
      it was taken up and accumulated within the brain. Further, IP injection of D-Asp
      had more beneficial effects on EAE severity than oral gavage. The concentration
      of the testosterone and 17beta-estradiol in D-Asp-IP group was significantly
      higher than that of the control group. There were no significant differences in
      the gene expression of cytokine and neurosteroid receptors between control, D-Asp
      IP, and D-Asp-Oral groups. However, IP treatment with D-Asp significantly reduced
      C-C motif chemokine ligand 2 and MMP-2 serum levels compared to control mice.
      CONCLUSION: IP injection of D-Asp had more beneficial effects on EAE severity,
      neurosteroid induction and reduction of inflammatory mediators than oral gavage.

PMID- 30289088
TI  - Cerebrovascular Injury Following Scorpion Sting and Snake Envenomation: A Case
      Series.
AB  - BACKGROUND: Neurological complications following snake and scorpion bite are
      diverse. Literature regarding patterns of cerebrovascular injury (CVI) and
      outcomes among these patients is scarce. This is a descriptive study of the
      clinical profile, brain imaging findings, mechanisms of injury, vascular
      territory involvement and outcomes of CVI following scorpion and snake
      envenomation, in a tertiary care center in South India.MethodologyPatients with
      scorpion sting- and snake envenomation-related complications were retrospectively
      enrolled. Neuroimaging was performed on five patients with each envenomation, and
      they were found to have neurological involvement. On imaging, three patients were
      found to have a CVI. Clinical, radiological parameters and outcomes of these
      patients were studied. We also performed a review of the literature and analyzed
      the finding of all the cases.ResultIn all, three patients each had evidence of
      CVI in imaging. An additional 32 reports of scorpion sting-related CVI and 35
      reports of snake envenomation-related CVI were identified from the literature.
      There was a male predominance among these patients. Mean age of the patients with
      scorpion sting was 42.8 years as compared with 33 years for the patients with
      snake envenomation. Features of severe envenomation were present in all patients.
      Persistently depressed sensorium and new-onset focal neurological deficits were
      seen in 70% of all patients. Infarcts were seen in 88% of patients with snake
      envenomation and 53% of patients with a scorpion sting. Mortality was 28% among
      patients with a scorpion sting as compared with 8% with snake envenomation.
      CONCLUSION: Cerebrovascular injuries are uncommon neurological manifestations
      following scorpion and snake envenomation. These tend to occur in younger
      patients. Infarcts are more common than bleeds.

PMID- 30289089
TI  - Reviewing indications for panendoscopy in the investigation of head and neck
      squamous cell carcinoma.
AB  - BACKGROUND: The role of panendoscopy in the modern investigation of head and neck
      cancer is changing with the development of improved radiological techniques, in
      office biopsy capabilities and the low rate of synchronous primary tumours. This
      study aimed to review the indications for panendoscopy in the investigation of
      newly diagnosed head and neck cancer. METHOD: A retrospective review was
      conducted of 186 patients with newly diagnosed head and neck cancer, between
      January 2014 and December 2015, at two tertiary centres. RESULTS: Obtaining a
      tissue diagnosis was the most common indication for panendoscopy (65 per cent),
      followed by surgical planning including transoral robotic surgery suitability
      assessment (22.6 per cent), and the investigation of carcinoma of an unknown
      primary (11.3 per cent). Two synchronous primary tumours were identified,
      generating a yield of 1.1 per cent. CONCLUSION: Panendoscopy remains integral in
      the assessment of transoral robotic surgery suitability. Refining indications for
      modern panendoscopy could reduce the need for this procedure in this cohort of
      patients.

PMID- 30289090
TI  - Added dietary cobalt or vitamin B12, or injecting vitamin B12 does not improve
      performance or indicators of ketosis in pre- and post-partum Holstein-Friesian
      dairy cows.
AB  - Vitamin B12 is synthesised in the rumen from cobalt (Co) and has a major role in
      metabolism in the peri-paturient period, although few studies have evaluated the
      effect of the dietary inclusion of Co, vitamin B12 or injecting vitamin B12 on
      the metabolism, health and performance of high yielding dairy cows. A total of 56
      Holstein-Friesian dairy cows received one of four treatments from 8 weeks before
      calving to 8 weeks post-calving: C, no added Co; DC, additional 0.2 mg Co/kg dry
      matter (DM); DB, additional 0.68 mg vitamin B12/kg DM; IB, intra-muscular
      injection of vitamin B12 to supply 0.71 mg/cow per day prepartum and 1.42 mg/cow
      per day post-partum. The basal and lactation rations both contained 0.21 mg Co/kg
      DM. Cows were weighed and condition scored at drying off, 4 weeks before calving,
      within 24 h of calving and at 2, 4 and 8 weeks post-calving, with blood samples
      collected at drying off, 2 weeks pre-calving, calving and 2, 4 and 8 weeks post
      calving. Liver biopsy samples were collected from all animals at drying off and 4
      weeks post-calving. Live weight changed with time, but there was no effect of
      treatment (P>0.05), whereas cows receiving IB had the lowest mean body condition
      score and DB the highest (P0.05) with mean values of 21.6 kg/day, 39.6 kg/day and
      40.4 g/kg, respectively. Cows receiving IB had a higher plasma vitamin B12
      concentration than those receiving any of the other treatments (P0.05) of
      treatment on homocysteine or succinate concentrations, although mean plasma
      methylmalonic acid concentrations were lower (P=0.019) for cows receiving IB than
      for Control cows. Plasma beta-hydroxybutyrate concentrations increased sharply at
      calving followed by a decline, but there was no effect of treatment. Similarly,
      there was no effect (P>0.05) of treatment on plasma non-esterified fatty acids or
      glucose. Whole tract digestibility of DM and fibre measured at week 7 of
      lactation were similar between treatments, and there was little effect of
      treatment on the milk fatty acid profile except for C15:0, which was lower in
      cows receiving DC than IB (P<0.05). It is concluded that a basal dietary
      concentration of 0.21 mg Co/kg DM is sufficient to meet the requirements of high
      yielding dairy cows during the transition period, and there is little benefit
      from additional Co or vitamin B12.

PMID- 30289091
TI  - Estimating the health and socioeconomic effects of cousin marriage in South Asia.
AB  - The effects of marriage between biological relatives on the incidence of
      childhood genetic illness and mortality are of major policy significance, as
      rates of consanguinity exceed 50% in various countries. Empirical research on
      this question is complicated by the fact that consanguinity is often correlated
      with poverty and other unobserved characteristics of households, which may have
      independent effects on mortality. This study has developed an instrumental
      variables empirical strategy to re-examine this question, based on the concept
      that the availability of unmarried cousins of the opposite gender at the time of
      marriage creates quasi-random variation in the propensity to marry
      consanguineously. Using primary data collected in Bangladesh in 2006-07 and
      Pakistan in 2009-10, the study found that previous estimates of the impact of
      consanguinity on child health were biased and falsely precise. The study also
      empirically investigated the social and economic causes of consanguinity
      (including marital quality) and concludes that marrying a cousin can have
      positive economic effects for one's natal family, by allowing deferral of dowry
      payments until after marriage.

PMID- 30289092
TI  - Ossicular chain mobilisation versus reconstruction in surgery for isolated
      malleus and/or incus fixation: systematic review and meta-analysis.
AB  - OBJECTIVE: To compare post-operative audiometric outcomes for the two prevailing
      surgical approaches for isolated malleus and/or incus fixation: ossicular
      mobilisation with preservation of the ossicular chain, and disruption and
      reconstruction of the ossicular chain. METHODS: A search was conducted, in
      December 2016, of PubMed, Scopus, and Cumulative Index to Nursing and Allied
      Health Literature articles written in English. Papers presenting original data
      regarding post-operative audiometric outcomes in patients who underwent surgical
      treatment for malleus and/or incus fixation with a mobile and intact stapes were
      included. A risk of bias assessment was performed on the 14 selected papers and a
      tier system was developed. Meta-analysis was accomplished by comparing pooled
      rates of surgical success by chi-square test and calculating odds ratios by
      logistical regression. Analysis was performed using Revman5 and R
      software.Results and conclusionAnalysis of the literature revealed no differences
      in audiometric outcomes between ossicular chain mobilisation and ossicular chain
      reconstruction in patients with isolated malleus and/or incus fixation. A large,
      prospective study comparing both short- and long-term hearing results for
      ossicular chain mobilisation and ossicular chain reconstruction in this
      population may identify whether a difference in outcomes exists between the two
      approaches.

PMID- 30289093
TI  - Neighborhood structural characteristics and Mexican-origin adolescents'
      development.
AB  - Ethnic-racial and socioeconomic residential segregation are endemic in the United
      States, representing societal-level sociocultural processes that likely shape
      development. Considered alongside communities' abilities to respond to external
      forces, like stratification, in ways that promote youth adaptive functioning and
      mitigate maladaptive functioning, it is likely that residence in segregated
      neighborhoods during adolescence has both costs and benefits. We examined the
      influences that early adolescents' neighborhood structural characteristics,
      including Latino concentration and concentrated poverty, had on a range of
      developmentally salient downstream outcomes (i.e., internalizing, externalizing,
      prosocial behaviors, and ethnic-racial identity resolution) via implications for
      intermediate aspects of adolescents' community participation and engagement
      (i.e., ethnic-racial identity exploration, ethnic-racial discrimination from
      peers, and school attachment). These mediational mechanisms were tested
      prospectively across three waves (Mage w1-w3 = 12.79, 15.83, 17.37 years,
      respectively) in a sample of 733 Mexican-origin adolescents (48.8% female). We
      found higher neighborhood Latino concentration during early adolescence predicted
      greater school attachment and ethnic-racial identity exploration and lower
      discrimination from peers in middle adolescence. These benefits, in turn, were
      associated with lower externalizing and internalizing and higher ethnic-racial
      identity resolution and prosocial behaviors in late adolescence. Findings are
      discussed relative to major guidelines for integrating culture into development
      and psychopathology.

PMID- 30289094
TI  - Development and implementation of an advance care planning program in Catalonia,
      Spain.
AB  - OBJECTIVE: Implementation of an advance care planning (ACP) program for people
      with advanced chronic conditions is a complex process. The aims of this paper are
      to describe (1) the development of the ACP program in Catalonia, Spain, for
      patients with advanced chronic conditions and complex needs and (2) the
      preliminary results of the implementation of this program in health and social
      services. METHOD: The ACP program was developed and implemented in a four-stage
      process as follows: (1) design and organization of the project; (2) selection of
      the professionals to carry out the project; (3) creation of four working groups
      to develop the conceptual model, guidelines, training program, and perform a
      qualitative evaluation; and (4) project implementation.ResultThe following
      deliverables were completed: (1) conceptual framework document; (2) practical
      guidelines for the application of the ACP; (3) online training course (3,763
      healthcare professionals completed the online course, with an overall
      satisfaction rating of 8.4 on a 10-point scale); and (4) additional training
      activities (conferences, short courses, and seminars) in between 2015 and
      2017.Significance of resultsThis project was led by the Catalan Ministry of
      Health. The strengths of the project development include the contribution of a
      wide range of professionals from the entire region, approval by the Catalan
      Bioethics Committee and the Social Services Ethics Committee, and the ongoing
      validation by members of the community. A standardized online training course was
      offered to all primary care professionals and included as a quality indicator for
      continuing education for those professionals in the period 2016-2020. The main
      outcome of this project is the establishment of a pragmatic ACP throughout the
      region and training of the health and social care professionals involved in the
      care of advanced chronic patients.

PMID- 30289095
TI  - Effect of adding heterologous versus homologous bovine seminal plasma prior to
      cryopreservation on bull sperm quality after thawing.
AB  - SummaryThe aim of this study was to investigate the effect of adding homologous
      or heterologous bovine seminal plasma (SP) to SP-free sperm samples before
      freezing on sperm quality after thawing. Ejaculates from bulls of known fertility
      were used as a source of SP. The SP was removed from further aliquots of the same
      ejaculates by colloid centrifugation to create SP-free sperm samples; the
      resuspended sperm pellets were treated with homologous or heterologous SP from
      high or low fertility bulls at 0%, 1% or 5% before freezing. After thawing, sperm
      quality was evaluated by computer-assisted sperm analysis and flow cytometry for
      membrane integrity, reactive oxygen species, chromatin structure, mitochondrial
      membrane potential and protein tyrosine phosphorylation. Data were analysed using
      Proc MIXED, SAS(r). Post-hoc comparisons were adjusted for multiplicity using
      Tukey's method. The addition of SP resulted in significant differences in sperm
      quality, namely velocity class A, Velocity Straight Line (VSL), Velocity Average
      Path (VAP), Velocity Curved Line (VCL), Amplitude of Lateral Head Displacement
      (ALH), Hyperactive (HYP), reactive oxygen species (ROS) production and % DNA
      fragmentation index (DFI) (P<0.05 for each). Although adding 5% homologous SP
      from high fertility bulls was beneficial to sperm kinematics, 5% heterologous SP
      from high fertility bulls had a deleterious effect on chromatin integrity and on
      sperm velocity. In conclusion, adding SP may have either a beneficial effect or a
      deleterious effect depending on the individuals involved. It might be feasible to
      use this method to improve sperm quality in some circumstances.

PMID- 30289096
TI  - Propensity in low-grade oocytes for delayed germinal vesicle breakdown
      compromises the developmental ability of sub-optimal grade Bubalus bubalis
      oocytes.
AB  - SummaryMaturing oocytes have diverse developmental potential and good quality
      oocytes exhibit a better ability to attain physiological milestones in a time
      dependent manner. This situation necessitates the confirmation of oocyte
      developmental status more precisely under an in vitro embryo production (IVEP)
      regime. The aim of this study was to explain timely events in germinal vesicle
      breakdown (GVBD), an important milestone of oocyte nuclear maturation, to
      delineate the developmental capacity of Bubalus bubalis oocytes. In addition, the
      expression profile of genes responsible for GVBD was assessed in order to
      understand the molecular context responsible for GVBD. The chronology of GVBD
      events at different time intervals during in vitro maturation (IVM) suggests that
      the rate at which oocytes undergo GVBD was strikingly different in the brilliant
      cresyl blue (BCB)+ and BCB- groups. The expression of AKT and CDC25B genes for
      BCB+ oocytes was maximum at 8 h of IVM, and CCNB (cyclin B) peaked at around 10
      h, which suggested that GVBD was finished after 10 h in BCB+ oocytes, whereas the
      expression of AKT and CDC25B was found to peak at around 12-14 h of IVM. This
      difference consequently delays the GVBD event by 2-4 h in BCB- oocytes. Poor
      abundance of gene transcripts was mainly implicated in delay and lower rate of
      GVBD in BCB- oocytes which in turn strongly affected the translational ability of
      oocytes to blastocysts. The findings of this study support the idea that there is
      a propensity in sub-optimal grade oocytes for delayed GVBD that compromises the
      developmental ability of low grade buffalo oocytes. The study highlights the very
      small, but importantly vital and separate, time window of the GVBD event during
      which the competence levels of buffalo oocytes are altered along with their
      translational ability to develop into the prospective embryos.

PMID- 30289097
TI  - Going back to prospectively collected results with a probiotic for primary
      prevention of Clostridium difficile infection at a tertiary-care medical center.

PMID- 30289098
TI  - The effect of an infographic promotion on research dissemination and readership:
      A randomized controlled trial.
AB  - CLINICIAN'S CAPSULE What is known about the topic? Infographics are graphical
      illustrations of complex ideas that are broadly shared on social media platforms.
      What did this study ask? What is the effect of a social media strategy using
      infographics on the readership and dissemination of research articles? What did
      this study find? Infographic articles were associated with increased Altmetric
      scores and abstract views, but not full-text views. Why does this study matter to
      clinicians? The promotion of articles with infographics may increase awareness
      and dissemination of research findings among clinicians.

PMID- 30289099
TI  - Antioxidant and developmental capacity of retinol on the in vitro culture of
      rabbit embryos.
AB  - SummaryOxidative stress is a major cause of defective embryo development during
      in vitro culture. Retinoids are recognized as non-enzymatic antioxidants and may
      have an important role in the regulation of cell differentiation and vertebrate
      development. However, there are not enough reports discussing the antioxidant and
      developmental capacity of retinoids, including retinol (RT), on the in vitro
      development of embryos recovered from livestock animals, particularly in rabbit
      species. Therefore, morula embryos obtained from nulliparous Red Baladi rabbit
      does were cultured for 48 h in TCM199 medium in the absence of RT (control group)
      or in the presence of RT at concentrations of 10, 100 and 1000 nM. The
      developmental capacity to the hatched blastocyst stage, the antioxidant biomarker
      assay and the expression of several selected genes were analyzed in each RT
      group. The data show that RT significantly (P<0.001) promoted the embryo
      hatchability rate at the concentration of 1000 nM to 69.44% versus 29.71% for the
      control. The activity of malondialdehyde (MDA) level was significantly (P<0.05)
      lower in the RT groups than in the control group, while the total antioxidant
      capacity (TAC), superoxide dismutase (SOD) and glutathione peroxidase (GPx)
      activities were significantly (P<0.05) higher following treatment with RT.
      Furthermore, RT treatment considerably upregulated the relative expression of gap
      junction protein alpha 1 (GJA1), POU class 5 homeobox 1 (POU5F1) and superoxide
      dismutase 1 (SOD1) genes compared with the control group. The current study
      highlights the potential effects of RT as antioxidant in the culture medium on
      the in vitro development of rabbit embryos.

PMID- 30289100
TI  - Changes in body composition and meat quality in response to dietary amino acid
      provision in finishing broilers.
AB  - In order to control and optimize chicken quality products, it is necessary to
      improve the description of the responses to dietary amino acid (AA) concentration
      in terms of carcass composition and meat quality, especially during the finishing
      period. The aim of this study was to investigate the effects of Lysine (Lys, i.e.
      a limiting AA used as reference in AA nutrition) and AA other than Lys (AA
      effect). In total, 12 experimental diets were formulated with four levels of
      digestible Lys content (7, 8.5, 10 and 11.5 g/kg) combined with either a low (AA
      ), adequate control (AAc) and high (AA+) amount of other essential AA (EAA)
      expressed as a proportion of Lys. They were distributed to male Ross PM3 from 3
      to 5 weeks of age. No significant AA*Lys interaction was found for growth
      performance or carcass composition. Body weight and feed conversion ratio were
      significantly improved by addition of Lys but were impaired in broilers receiving
      the AA- diets, whereas breast meat yield and abdominal fat were only affected by
      Lys. No additional benefit was found when the relative amount of other EAA was
      increased. There was a significant AA*Lys interaction on most of the meat quality
      traits, including ultimate pH, color and drip loss, with a significant effect of
      both AA and Lys. For example, AA- combined with reduced Lys level favored the
      production of meat with high ultimate pH (>6.0), dark color and low drip loss
      whereas more acid, light and exudative meat (<5.85) was produced with AA+
      combined with a low Lys level. In conclusion, growth performance, carcass
      composition and meat quality are affected by the levels of dietary Lys and AA in
      finishing broilers. In addition, interactive responses to Lys and AA are found on
      meat quality traits, leading to great variations in breast pHu, color and drip
      loss according AA balance or imbalance.

PMID- 30289101
TI  - Pumilio1 phosphorylation precedes translational activation of its target mRNA in
      zebrafish oocytes.
AB  - SummaryTranslational regulation of mRNAs is crucial for promoting various
      cellular and developmental processes. Pumilio1 (Pum1) has been shown to play key
      roles in translational regulation of target mRNAs in many systems of diverse
      organisms. In zebrafish immature oocytes, Pum1 was shown to bind to cyclin B1
      mRNA and promote the formation of cyclin B1 RNA granules. This Pum1-mediated RNA
      granule formation seemed critical to determine the timing of translational
      activation of cyclin B1 mRNA during oocyte maturation, leading to activation of
      maturation/M-phase-promoting factor (MPF) at the appropriate timing. Despite its
      fundamental importance, the mechanisms of translational regulation by Pum1 remain
      elusive. In this study, we examined the phosphorylation of Pum1 as a first step
      to understand the mechanisms of Pum1-mediated translation. SDS-PAGE analyses and
      phosphatase treatments showed that Pum1 was phosphorylated at multiple sites
      during oocyte maturation. This phosphorylation began in an early period after
      induction of oocyte maturation, which preceded the polyadenylation of cyclin B1
      mRNA. Interestingly, depolymerization of actin filaments in immature oocytes
      caused phosphorylation of Pum1, disassembly of cyclin B1 RNA granules, and
      polyadenylation of cyclin B1 mRNA but not translational activation of the mRNA.
      Overexpression of the Pum1 N-terminus prevented the phosphorylation of Pum1,
      disassembly of cyclin B1 RNA granules, and translational activation of the mRNA
      even after induction of oocyte maturation. These results suggest that Pum1
      phosphorylation in the early period of oocyte maturation is one of the key
      processes for promoting the disassembly of cyclin B1 RNA granules and
      translational activation of target mRNA.

PMID- 30289103
TI  - Meniere's disease: 'a riddle wrapped in a mystery inside an enigma'. Has the key
      been found?

PMID- 30289102
TI  - Effect of aquaporin 3 knockdown by RNA interference on antrum formation in sheep
      secondary follicles cultured in vitro.
AB  - SummaryThe objectives were to develop an effective protocol for transfection of
      ovine secondary follicles and to assess the effect of attenuating aquaporin 3
      (AQP3) using a small interfering RNA (siRNA-AQP3) on antrum formation and
      follicular growth in vitro. Various combinations of Lipofectamine(r) volumes
      (0.5, 0.75 or 1.0 ul), fluorescent oligonucleotide (BLOCK-iT TM) concentrations
      (3.18, 27.12 or 36.16 nM) and exposure times (12, 14, 16, 18 or 20 h) were
      tested. The BLOCK-iTTM was replaced by siRNA-AQP3 in the transfection complex.
      Ovine secondary follicles were isolated and cultured in vitro for 6 days using
      standard protocols. Follicles were transfected on day 0 or 3 or on both days (0
      and 3) and then cultured for an additional 3 or 6 days. As revealed by the
      fluorescence signal, the Lipofectamine(r)/BLOCK-iTTM complex (0.75 ul + 27.12 nM
      by 12 h of incubation) crossed the basement membrane and granulosa cell and
      reached the oocytes. In general, the rate of intact follicles was higher and the
      rate of antrum formation was lower in transfected follicles compared with control
      follicles. In conclusion, ovine secondary follicles can be successfully
      transfected during in vitro culture, and siRNA-mediated attenuation of AQP3 gene
      reduced antrum formation of secondary follicles.

PMID- 30289104
TI  - Wound healing after tonsillectomy - a review of the literature.
AB  - OBJECTIVE: To summarise the available literature related to wound healing post
      tonsillectomy, including the stages of healing, experimental models for assessing
      healing (in animals and humans) and the various factors that affect wound
      healing. METHODS: A search of the English literature was conducted using the Ovid
      Medline database, with the search terms 'tonsillectomy' or 'tonsil' and 'wound
      healing'. Thirty-one articles that objectively assessed tonsillectomy wound
      healing were included for analysis. RESULTS: The majority of assessments in
      humans investigating tonsillectomy wound healing involve serial direct clinical
      examinations of the oral cavity. Many patient and surgical factors have been
      shown to affect wound healing after tonsillectomy. There is some research to
      suggest that the administration of adjunctive treatment in the post-operative
      period may be beneficial to tonsillectomy wound healing. CONCLUSION: Wound
      healing post tonsillectomy has been poorly researched. Having a better
      understanding of the process of wound healing would allow surgeons to potentially
      prevent, anticipate and manage complications from the surgery that arise as part
      of the healing process.

PMID- 30289105
TI  - Awareness of High Blood Pressure by Nativity Among Black Men: Implications for
      Interpreting the Immigrant Health Paradox.
AB  - INTRODUCTION: Differences in the social determinants of health and cardiovascular
      health outcomes by nativity have implications for understanding the immigrant
      health paradox among black immigrants. We aimed to understand whether blood
      pressure awareness, a precursor to achieving blood pressure control among
      hypertensive patients, varied by nativity among a sample of black men. METHODS:
      Data were collected from 2010 through 2014. In 2016, we conducted logistic
      regression models using data from a large sample of urban-dwelling middle-aged
      and older black men. All men in the study had measured high blood pressure at the
      time of enrollment and were also asked whether they were aware of having high
      blood pressure. Independent variables included demographics, socioeconomic
      status, access to care, and health-related behaviors. RESULTS: Foreign-born
      participants were significantly less likely than US-born participants to report
      awareness of having high blood pressure (P < .001). We observed a significant
      positive relationship between proportion of life spent in the US and being aware
      of having hypertension (beta = 0.863; 95% CI, 0.412-1.314; P < .001). This
      relationship remained after adjusting the model for salient independent variables
      (beta = 0.337; 95% CI, 0.041-0.634; P = .03). CONCLUSIONS: Difference in
      hypertension awareness by nativity may skew surveillance estimates used to track
      health disparities by large heterogeneous racial categories. Our results also
      indicate that prior health care experience and circumstances should be considered
      when studying the immigrant health paradox.

PMID- 30289106
TI  - Inpatient Medicaid Usage and Expenditure Patterns After Changes in Supplemental
      Nutrition Assistance Program Benefit Levels.
AB  - INTRODUCTION: Food insecurity worsens health outcomes and is associated with
      increased health care usage and expenditures. The Supplemental Nutrition
      Assistance Program (SNAP) reduces but does not eliminate recipients' food
      insecurity. We sought to determine whether inpatient Medicaid usage and
      expenditure patterns responded to an April 2009 increase in SNAP benefit levels
      and a subsequent November 2013 decrease. METHODS: Interrupted time series models
      estimated responses to the 2009 and 2013 SNAP changes in the Medicaid population,
      compared responses between Medicaid and Medicare recipients, and compared
      responses between Medicaid recipients with different likelihoods of having a
      disability. Analyses used 2006 through 2014 Healthcare Cost and Utilization
      Project National (previously Nationwide) Inpatient Sample data. RESULTS: After
      the 2009 SNAP increase, Medicaid admission growth fell nationally from 0.80 to
      0.35 percentage points per month (a difference of -0.45; 95% CI, -0.72 to -0.19),
      adjusting for enrollment. After the 2013 SNAP decrease, admission growth rose to
      2.42 percentage points per month (a difference of 2.07; 95% CI, 0.68 to 3.46).
      Inflation-adjusted monthly Medicaid expenditures followed similar patterns and
      were associated with $26.5 billion (in 2006 dollars) in reduced expenditures over
      the 55 months of the SNAP increase, and $6.4 billion (in 2006 dollars) in
      additional expenditures over the first 14 months after the SNAP decrease. Effects
      were elevated for Medicaid compared with Medicare recipients and among people
      with a high likelihood of having a disability. CONCLUSION: Although alternative
      causal explanations warrant consideration, changes in SNAP benefit levels were
      associated with changes in inpatient Medicaid usage and cost patterns.

PMID- 30289107
TI  - Geographic Availability of Low-Dose Computed Tomography for Lung Cancer Screening
      in the United States, 2017.

PMID- 30289109
TI  - Laparoscopic Reduction of Intussusception in Children in Restricted Environment:
      Our Initial Experience Supports Timely Resort to Minimally Invasive Surgery.

PMID- 30289108
TI  - Genome-wide Scan Identifies Role for AOX1 in Prostate Cancer Survival.
AB  - BACKGROUND: Most men diagnosed with prostate cancer have low-risk cancers. How to
      predict prostate cancer progression at the time of diagnosis remains challenging.
      OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) associated with
      death from prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Blood samples from
      11 506 men in Sweden were collected during 1991-1996. Of these, 1053 men were
      diagnosed with prostate cancer and 245 died from the disease. Stage and grade at
      diagnosis and outcome information were obtained, and DNA from all cases was
      genotyped. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A total of 6 126 633
      SNPs were tested for association with prostate-cancer-specific survival time
      using a Cox proportional hazard model, adjusted for age, stage, and grade at
      diagnosis. A value of 1*10-6 was used as suggestive significance threshold.
      Positive candidate SNPs were tested for association with gene expression using
      expression quantitative trait locus analysis. RESULTS AND LIMITATIONS: We found
      12 SNPs at seven independent loci associated with prostate-cancer-specific
      survival time. One of 6 126 633 SNPs tested reached genome-wide significance
      (p<5*10-8) and replicated in an independent cohort: rs73055188 (p=5.27*10-9, per
      allele hazard ratio [HR]=2.27, 95% confidence interval [CI] 1.72-2.98) in the
      AOX1 gene. A second SNP reached a suggestive level of significance (p<1*10-6) and
      replicated in an independent cohort: rs2702185 (p=7.1*10-7, per-allele HR=2.55,
      95% CI=1.76-3.69) in the SMG7 gene. The SNP rs73055188 is correlated with AOX1
      expression levels, which is associated with biochemical recurrence of prostate
      cancer in independent cohorts. This association is yet to be validated in other
      ethnic groups. CONCLUSIONS: The SNP rs73055188 at the AOX1 locus is associated
      with prostate-cancer-specific survival time, and AOX1 gene expression level is
      correlated with biochemical recurrence of prostate cancer. PATIENT SUMMARY: We
      identify two genetic markers that are associated with prostate-cancer-specific
      survival time.

PMID- 30289110
TI  - Endobronchial ultrasound: Echoing in the field of pediatrics.
AB  - Endobronchial ultrasound (EBUS) is a useful technique for the diagnosis and
      staging of the lung and mediastinal lesions, which is crucial for selecting
      treatment protocol. Under EBUS guidance, transbronchial needle aspiration (TBNA)
      is widely applied for obtaining specimens for histological, cytological, and
      molecular evaluation. Recently, the EBUS scope designed for adults has been used
      in large pediatric candidates. The presence of lung masses and mediastinal
      lymphadenopathy in the pediatric population presents a diagnostic challenge;
      however, EBUS is a promising tool for pediatricians to address these challenging
      issues. In some centers, the adult EBUS echobronchoscope is applied in
      transesophageal procedures for pediatric patients. EBUS-guided TBNA can also be
      used to perform minimally invasive interventional therapy, such as fiducial
      marker placement for assisting precision radiation, brachytherapy, and
      radiofrequency ablation therapy. With the development of EBUS equipment designed
      specifically for children, pediatric EBUS will play an increasingly important
      role.

PMID- 30289111
TI  - Painful tumors of the skin - from ENGLAND to LEND AN EGG to BLEND TAN EGG.

PMID- 30289112
TI  - Congenital alopecia of eyebrow.

PMID- 30289113
TI  - Low-dose adalimumab biosimilar (ZRC-3197) in the treatment of hidradenitis
      suppurativa.

PMID- 30289114
TI  - Hemophagocytic lymphohistiocytosis: A rare, potentially fatal complication in
      subcutaneous panniculitis like T cell lymphoma.
AB  - Subcutaneous panniculitis-like T cell lymphoma is a rare subtype of cutaneous
      lymphomas with distinct clinical, histological and immunophenotypic
      characteristics, as well as an indolent clinical course. Rarely, it may be
      complicated with hemophagocytic lymphohistiocytosis: a hyperinflammatory syndrome
      which, if not diagnosed early, carries a dismal outcome. In this article, we
      describe a case of subcutaneous panniculitis-like T cell lymphoma in a middle
      aged female patient which was complicated with secondary hemophagocytic
      lymphohistiocytosis with a favorable outcome following etoposide-based therapy.
      The various histological mimics of subcutaneous panniculitis-like T cell lymphoma
      and the management options are also briefly discussed.

PMID- 30289115
TI  - Histoid leprosy presenting with figurate lesions: A unique and rare presentation.

PMID- 30289116
TI  - Cutaneous epithelioid hemangioendothelioma: A rare presentation.

PMID- 30289117
TI  - Adverse cutaneous events after laser epilation in patients with photodermatosis.

PMID- 30289118
TI  - Scleredema of Buschke associated with lichen sclerosus: Three cases.
AB  - Scleredema adultorum of Buschke is a rare fibromucinous, scleroderma-like
      connective tissue disease most commonly found in a post-infectious setting or
      linked to hematological disorders or diabetes. Lichen sclerosus et atrophicus is
      an autoimmune condition only in 2.5% of cases localized exclusively at an
      extragenital site, occurring in up to 34% of patients in association with other
      autoimmune diseases such as vitiligo, thyroid disorders, alopecia areata, lichen
      planus, morphea, pernicious anemia and systemic lupus erythematosus. In
      particular, a stronger link with an autoimmune background in lichen sclerosus et
      atrophicus has been observed in women who showed higher prevalence for autoimmune
      conditions and circulating autoantibodies. Literature reveals a genetic
      susceptibility linked to specific HLA types. We report three patients who
      developed lichen sclerosus et atrophicus superimposed on skin involved by
      scleredema adultorum of Buschke. Although the association of lichen sclerosus et
      atrophicus with scleredema adultorum of Buschke could be coincidental, both
      diseases could be considered part of the spectrum of sclerodermoid disorders with
      common underlying pathogenetic mechanisms; which could explain the sequential or
      simultaneous occurrence of both lesions in our patients.

PMID- 30289119
TI  - Co-localization of immunobullous diseases at sites of dermatophytoses:
      Koebnerisation or a coincidence?

PMID- 30289120
TI  - 'End of the road for terbinafine' in dermatophytosis: Is it a valid conclusion?

PMID- 30289121
TI  - Dermoscopic features of three cases of Langerhans cell histiocytosis.

PMID- 30289122
TI  - Authors' reply.

PMID- 30289124
TI  - Correction: Design, synthesis, and evaluation of bitopic arylpiperazine
      phthalimides as selective dopamine D3 receptor agonists.
AB  - [This corrects the article DOI: 10.1039/C8MD00237A.].

PMID- 30289123
TI  - Clinical Effectiveness of Er: YAG Lasers Adjunct to Scaling and Root Planing in
      Non-Surgical Treatment of Chronic Periodontitis: A Meta-Analysis of Randomized
      Controlled Trials.
AB  - BACKGROUND Er: YAG lasers (ERLs) show suitable characteristics for scaling and
      root planing, but previous studies have drawn conflicting conclusions. This meta
      analysis aimed to systematically appraise the available evidence concerning the
      effectiveness of ERLs as an adjunct to scaling and root planing (SRP) for non
      surgical periodontal treatment. MATERIAL AND METHODS Randomized controlled trials
      (RCTs) comparing ERLs+SRP with SRP alone for the treatment of chronic
      periodontitis were searched in 9 electronic biomedical databases up to January
      2018. The weighted mean differences (WMDs) and 95% confidence intervals (CIs)
      were counted for probing depth (PD) reduction, clinical attachment level (CAL)
      gain, and visual analog scale (VAS) score. Heterogeneity was evaluated with the
      I2 statistic for interstudy comparisons and the chi2-based Q statistic for intra
      study comparisons. Sensitivity analysis was conducted by switching to a random or
      fixed effect model based on the heterogeneity. Publication bias was measured by
      Begg's test. RESULTS Ten related RCTs met the inclusion criteria. There were
      statistically significant differences in the assessed clinical parameters at the
      three-month follow-up: PD reduction (WMD=0.32, 95%CI range from 0.14 to 0.51,
      p<0.001; p=0.003, I2=69.7%); CAL gain (WMD=0.31, 95%CI range from 0.22 to 0.40,
      p<0.001; p=0.209, I2=28.8%); and VAS scores (WMD=-1.38, 95%CI range from -2.45 to
      -0.31, p<0.001; p=0.182, I2=44%). There were no significant differences at the
      six- and twelve-month follow-ups. Sensitivity analysis revealed that the results
      were consistent. No evidence of publication bias was detected. CONCLUSIONS This
      systematic analysis demonstrated that ERLs+SRP provides additional short-term
      effectiveness and that patients experience less pain compared to SRP. There were
      no significant differences at the medium-term and long-term follow-ups. Long-term
      well-designed RCTs are required.

PMID- 30289125
TI  - Determinants of preterm birth at Jimma University Medical Center, southwest
      Ethiopia.
AB  - Background: Preterm birth is the second leading cause of death next to pneumonia
      in children aged <5 years and the single-most important cause of death in the
      first month of life. Research examining determinants of preterm birth in Ethiopia
      is limited. Therefore, this study aimed to determine risk factors associated with
      preterm births at Jimma University Medical Center in southwest Ethiopia. Methods:
      This unmatched case-control study was conducted from March 15 to April 1, 2017
      from medical records of mothers and newborns delivered at Jimma University
      Medical Center from January 1 to December 30, 2016. Data were extracted using a
      structured checklist for cases (preterm) and controls (term) by reviewing
      maternal and newborn medical records using a simple random-sampling technique.
      Risk factors for preterm delivery were determined using bivariate and
      multivariate logistic regression models. Statistically significant associations
      were declared at P<0.05. Results: The present study evaluated 218 maternal and
      newborn cases and 438 controls. Risk factors identified were history of previous
      preterm birth (AOR 6.4, 95% CI 2.9-13.9), preeclampsia (AOR 6.6, 95% CI 3.3
      13.4), premature membrane rupture (AOR 11.7, 95% CI 6.2-21.9), antenatal care of
      fewer than four visits (AOR 4.8, 95% CI 1.2-19), birth interval <2 years (AOR
      2.7, 95% CI 1.7-4.5), and multiple pregnancies (AOR 4.5, 95% CI 2.4-8.5).
      Conclusion: History of previous preterm births, preeclampsia, premature membrane
      rapture, antenatal care of fewer than four visits, birth interval <2 years, and
      multiple pregnancies were found to have a possible causal relationship with
      preterm births. Therefore, similar further studies should be conducted to
      generate more population-based evidence on determinants of preterm births.

PMID- 30289126
TI  - Erratum: Publisher Correction to Hepatology, Medicine and Policy: Articles with
      DOIs 10.1186/s41124-017-0024-1, 10.1186/s41124-017-0025-0, 10.1186/s41124-017
      0026-z and 10.1186/s41124-017-0027-y.
AB  - [This corrects the article DOI: 10.1186/s41124-017-0027-y.][This corrects the
      article DOI: 10.1186/s41124-017-0026-z.][This corrects the article DOI:
      10.1186/s41124-017-0025-0.][This corrects the article DOI: 10.1186/s41124-017
      0024-1.].

PMID- 30289127
TI  - Correction: Correction: Hypoxia inducible factor (HIF) as a model for studying
      inhibition of protein-protein interactions.
AB  - [This corrects the article DOI: 10.1039/C7SC90030A.].

PMID- 30289128
TI  - Renal biopsy: it is time for pragmatism and consensus.
AB  - To obtain truly informed consent, we must be able to advise our patients
      accurately about the relative risk and benefit of any treatment plan.
      Percutaneous renal biopsy remains the gold standard investigation in the
      evaluation of intrinsic renal disease. There have been significant improvements
      in practice over the past decades with regards to percutaneous renal biopsy.
      Across centres, we appear now to have reached agreement on many aspects of this
      procedure, such as the need for blood pressure control, avoidance of
      coagulopathy, use of spring-loaded needles under direct imaging guidance and a
      need to monitor for complications. The authors from Rush University Medical
      Centre provide reassurance that renal biopsy in the modern era remains a safe
      procedure with a low rate of significant bleeding. There remain areas of
      divergence in practice that may have unintended and deleterious consequences:
      administration of desmopressin and discontinuation of aspirin, for example, both
      carry a risk of thrombosis. It is our opinion that it is time to reach consensus
      on our interpretation of the available data and to draw up guidelines to
      standardize our biopsy practice internationally.

PMID- 30289129
TI  - Risk of percutaneous renal biopsy of native kidneys in the evaluation of acute
      kidney injury.
AB  - Background: Percutaneous renal biopsy (PRB) of native kidneys (NKs) to better
      understand and treat acute kidney injury (AKI) is being advocated, but little is
      known about the risk of complications. Methods: We performed a retrospective
      study of PRB of NKs in 955 adults from 1991 to 2015 at an academic medical center
      with real-time ultrasound and automated biopsy needles. Patients undergoing PRB
      for evaluation of AKI (n = 160) were compared with 795 patients biopsied for
      other reasons (not-AKI) for postbiopsy complications [need for transfusion of
      packed red blood cells (PRBCs), an interventional radiologic or surgical
      procedure, readmission or death]. Results: Patients biopsied for AKI were older
      (58 +/- 16 versus 44 +/- 16 years; P < 0.0001), with a higher serum creatinine
      (SCr) (4.5 +/- 2.7 versus 1.8 +/- 1.6 mg/dL; P < 0.0001) and lower hemoglobin
      (Hgb) (10.4 +/- 1.7 versus 12.1 +/- 2.1; P < 0.0001) and a greater proportion had
      an abnormal bleeding time (12.5% versus 7.4%, P 0.04), partial thromboplastin
      time (15.2% versus 5.3%, P < 0.0001) and/or prothrombin time (27.0% versus 12.8%;
      P < 0.0001) compared with not-AKI patients. Complications post-PRB were
      significantly greater in patients biopsied for AKI {11.3% versus 6.7%; P=0.04;
      odds ratio [OR] 1.78 [95% confidence interval (CI) 1.01-3.12]} with patients
      biopsied for AKI requiring more blood transfusions (10.0% versus 5.3%; P 0.02; OR
      2.04 (95% CI 1.12-3.74)]. By multivariate analysis, baseline features predictive
      of a complication were increased SCr and decreased Hgb level, as well as female
      gender and increased systolic blood pressure. Conclusion: Patients biopsied for
      evaluation of AKI are at greater risk of complications due to increased risk
      factors.

PMID- 30289130
TI  - Comparison of native and transplant kidney biopsies: diagnostic yield and
      complications.
AB  - Background: The safety and adequacy are established for the native percutaneous
      renal biopsy (PRB) but no prospective studies exist that directly compare these
      with transplant PRB. Methods: From 1995 to 2015, 1705 adults underwent
      percutaneous native [native renal biopsy (NRB)] or transplant renal biopsy (TRB)
      by the Nephrology service. Real-time ultrasound and automated biopsy needles
      (NRB, 14 or 16 gauge; TRB, 16 gauge) were used. Patients were observed for 24 h
      (NRB) or 8 h (TRB) post-procedure. Adequacy was defined as tissue required for
      diagnosis plus glomerular yield. Complications were defined as those resulting in
      the need for an intervention, such as surgery, interventional radiologic
      procedure, readmission, blood transfusion and death. Data were collected
      prospectively in all biopsies. Results: At the time of biopsy, NRB patients were
      younger (mean +/- SD, 47 +/- 17 versus 50 +/- 14 years, P < 0.0001) and more
      often female (62 versus 48%, P < 0.0001) compared with TRB. A fellow supervised
      by an attending performed the procedure in 91% of NRB compared with 63% of TRB (P
      < 0.0001). TRB patients were more hypertensive [systolic blood pressure (SBP) 140
      +/- 22 versus 133 +/- 18 mmHg, P < 0.0001] and had a higher serum creatinine (3.1
      +/- 1.8 versus 2.3 +/- 2.2 mg/dL, P < 0.0001), activated partial thromboplastin
      time (28 +/- 4.3 versus 27 +/- 5 s, P < 0.0001) as well as lower hemoglobin (Hgb)
      (11.2 +/- 1.8 versus 11.7 +/- 2.1 g/dL, P < 0.0001) compared with NRB. Adequate
      tissue for diagnosis was obtained in > 99% of NRB and TRB (P = 0.71). Compared
      with TRB, NRB had a greater drop in Hgb after the biopsy (0.97 +/- 1.1 versus
      0.73 +/- 1.3 g/dL, P < 0.0001), a higher complication rate (6.5 versus 3.9%, P =
      0.02) and higher transfusion rate (5.2 versus 3.3%, P = 0.045). There was one
      death in each group attributed to the biopsy. Conclusions: Although death is
      equally rare, the complication rate is higher in NRB compared with TRB despite
      TRB having more of the traditional risk factors for bleeding. Differences in
      technique, operator (fellow or attending) or needle gauge may explain this
      variability.

PMID- 30289131
TI  - Unravelling drug-induced hypertension: molecular mechanisms of aldosterone
      independent mineralocorticoid receptor activation by posaconazole.
AB  - Drug-induced hypertension offers the opportunity to further understand pathways
      involved in the regulation of blood pressure. Posaconazole is an antifungal agent
      known to induce hypertension and hypokalaemia. In recent months, a flurry of
      reports has unravelled the metabolic processes involved. In this issue of CKJ,
      Barton K, Davis TK, Marshall B et al. Posaconazole-induced hypertension and
      hypokalemia due to inhibition of the 11beta-hydroxylase enzyme. Clin Kidney J
      2018; 11: 691-693 present convincing evidence of 11beta-hydroxylase inhibition
      resulting in a biochemical syndrome resembling genetic congenital adrenal
      hyperplasia and characterized by high 11-deoxycorticosterone and 11-deoxycortisol
      levels as well as androgen levels. This adds to prior evidence supporting
      inhibition of 11beta-hydroxysteroid dehydrogenase 2, the enzyme that inactivates
      cortisol in aldosterone-sensitive tissues such as the kidneys, yielding a
      syndrome resembling genetic apparent mineralocorticoid excess or licorice
      toxicity, characterized by a high cortisol/cortisone ratio.

PMID- 30289132
TI  - Posaconazole-induced hypertension and hypokalemia due to inhibition of the 11beta
      hydroxylase enzyme.
AB  - Posaconazole is an antifungal therapy reported to cause incident hypertension.
      Hypokalemia is also a known side effect. The combination of hypertension and
      hypokalemia suggests mineralocorticoid excess. We present the case of a 15-year
      old adolescent male with hypertensive urgency while on prophylactic posaconazole
      therapy for a combined immunodeficiency. We identify the mechanism of
      posaconazole-induced hypertension to be inhibition of the 11beta-hydroxylase
      enzyme, resulting in elevated levels of the mineralocorticoid receptor activator
      deoxycorticosterone. Loss of function of the 11beta-hydroxylase enzyme is
      responsible for a rare form of congenital adrenal hyperplasia and can be
      associated with life-threatening adrenal crisis.

PMID- 30289133
TI  - Assessing the capability of in silico mutation protocols for predicting the
      finite temperature conformation of amino acids.
AB  - Mutation protocols are a key tool in computational biophysics for modelling
      unknown side chain conformations. In particular, these protocols are used to
      generate the starting structures for molecular dynamics simulations. The accuracy
      of the initial side chain and backbone placement is crucial to obtain a stable
      and quickly converging simulation. In this work, we assessed the performance of
      several mutation protocols in predicting the most probable conformer observed in
      finite temperature molecular dynamics simulations for a set of protein-peptide
      crystals differing only by single-point mutations in the peptide sequence. Our
      results show that several programs which predict well the crystal conformations
      fail to predict the most probable finite temperature configuration. Methods
      relying on backbone-dependent rotamer libraries have, in general, a better
      performance, but even the best protocol fails in predicting approximately 30% of
      the mutations.

PMID- 30289134
TI  - Fluorescence response from the surface states of nitrogen-doped carbon nanodots:
      evidence of a heterogeneous population of molecular-sized fluorophores.
AB  - Fluorescent Nitrogen-doped Carbon Nanodots (NCDs) of ~4 nm diameter were prepared
      by acid-driven microwave irradiation of DMF solvent. Spectroscopic studies of the
      NCDs demonstrated that excitation of the carbon core did not contribute any
      fluorescence emission. Instead, the emission originated exclusively from the
      surface states. The fluorescence featured a prominent red edge excitation shift
      (REES), while changing the excitation wavelength over ~0.5 eV indicated the
      emergence of different emitter species in the temporal evolution of fluorescence.
      These results combined to indicate a large degree of heterogeneity in the
      population of these surface-localized emitters, so that working with different
      excitation energies produced different sets of excited surface fluorophores that
      evolved independently of each other. Fluorescence anisotropy dynamics in the NCDs
      was attributable to the reorientational motion of the surface fluorophores which
      was decoupled from the rotational diffusion of the carbon core of the NCD. The
      anisotropy decay rates revealed that the fluorophores had size comparable to
      typical organic fluorophores, irrespective of excitation energy.

PMID- 30289135
TI  - Unveiling CO adsorption on Cu surfaces: new insights from molecular orbital
      principles.
AB  - CO adsorption on Cu(100), (110), and (111) surfaces has been extensively studied
      using Kohn-Sham density functional theory calculations. A holistic analysis of
      adsorption energies, charge transfer, and structural changes has been employed to
      highlight the variations in adsorption mechanisms upon changing the surface type
      and the adsorption site. Each surface, with its unique arrangement of atoms,
      resulted in a varying adsorbate behavior, although the same adsorption site is
      considered. This directly reflects the influence of the atomic arrangement on the
      substrate-adsorbate interactions. Site-interactions are rigorously investigated
      using molecular-orbital and charge transfer principles taking into account the
      fundamental interaction of frontier (5sigma and 2pi*) orbitals. Considering the
      effects of the surface atomic arrangement and density of metal interacting
      orbitals, along with the relative d-5sigma and d-2pi* energy spacings, the
      calculated adsorption preference to higher coordination sites is explained, which
      also revealed valuable interpretations to the well-known DFT CO adsorption
      puzzle. In addition, we studied the perturbations occurring upon adsorption to
      the 3sigma and 1pi orbitals, which hold the internal C-O bond. Studying 3sigma
      and 1pi orbital perturbations provided a wealth of theoretical interpretations
      for the varying behavior of the adsorbate molecule when similar adsorption sites
      are compared at different facets.

PMID- 30289136
TI  - High performance sorption and desorption behaviours at high working temperatures
      of ammonia gas in a cobalt-substituted Prussian blue analogue.
AB  - As an adsorbent of gaseous ammonia, cobalt hexacyanocobaltate
      (CoII3[CoIII(CN)6]2) was proved to have good sorption even at high temperatures,
      with thermal recyclability in sorption-desorption cycles. The maximum sorption
      capacities evaluated with a dual-site Langmuir model are 25.2, 18.6, 8.6, and 2.1
      mmol g-1 at 20, 100, 150, and 250  degrees C, respectively.

PMID- 30289137
TI  - Transformation of cellulosic saccharides into alkyl glucosides catalyzed by
      bifunctional ionic liquids.
AB  - Three kinds of hydrophobic/acidic bifunctional ionic liquids, which contain two
      different anions, were synthesized and utilized as catalysts for the conversion
      of cellulosic saccharides into alkyl glucosides, which exhibit a high catalytic
      conversion for cellobiose and cellulose with a low degree of crystallinity; the
      catalyst can be easily recovered and reused.

PMID- 30289138
TI  - A two-photon fluorescent probe for ratiometric visualization of hypochlorous acid
      in live cells and animals based on a selenide oxidation/elimination tandem
      reaction.
AB  - Utilizing the oxidation/elimination tandem reaction of the alpha-phenylseleno
      carbonyl moiety, a two-photon fluorescent probe for ratiometric visualization of
      hypochlorous acid was developed. Its superior sensing performance and practical
      applications were well demonstrated.

PMID- 30289139
TI  - Geometric deconstruction of core and electron activation of a pi-system in a
      series of deformed porphyrins: mimics of heme.
AB  - The predominant distortion of heme is responsible for its electronic activity,
      catalytic ability and spectral properties. In this work, altogether 12 new X-ray
      structures of saddled, waved and ruffled porphyrins are reported. Three types of
      deformed porphyrins as mimics of heme were evaluated and analyzed by geometric
      deconstruction, spectral comparison, and electrochemical tracking, which shows a
      unique relationship of deformation fashions and distortion degree to the geometry
      of the core and electron transfer ability of rings in these enzyme containing
      porphyrins. These mimics can adjust their core geometry for changing the
      structures of potential metals; while for rings themselves, they can also
      regulate the electron activity by switching the HOMO of the large pi systems.
      These deformed porphyrins can be used as ideal mimics for heme. These findings
      help us to understand the principle and contribution of these deformations to
      electron transfer in catalytic oxidation and photoreactions. The nonplanar mimics
      have been synthesized through a modular synthetic approach under Adler-Longo or
      Lindsey condensation conditions.

PMID- 30289140
TI  - Trigonal layered rosiaite-related antiferromagnet MnSnTeO6: ion-exchange
      preparation, structure and magnetic properties.
AB  - Ion-exchange treatment of Na2SnTeO6 in molten salt mixtures resulted in rosiaite
      (PbSb2O6)-related MnSnTeO6. Its crystal structure was refined by the Rietveld
      method. Of the three possible models of Sn/Te distribution, the disordered model
      (P3[combining macron]1m, a = 5.23093(11) A, c = 4.62430(16) A) was preferred
      based on bond distances. However, it is supposed that each individual (SnTeO6)2-
      layer retains complete ordering of the precursor and the apparent disorder is
      only due to stacking faults. Magnetic studies have shown that MnSnTeO6 orders
      antiferromagnetically at Neel temperature TN = 9.8 K. The effective magnetic
      moment reasonably agrees with theoretical estimations assuming high-spin
      configuration of Mn2+ (S = 5/2). Electron spin resonance reveals spin dynamics in
      accordance with antiferromagnetic ordering. Moreover, critical broadening of ESR
      linewidth indicates the low-dimensional type of exchange interactions. Based on
      the temperature and field-dependent magnetization studies, the magnetic phase
      diagram of the new compound was constructed.

PMID- 30289141
TI  - Light-induced morphological transition between unconjugated bilirubin
      photoisomers.
AB  - Morphology switching by an external stimulus creates the possibility to detect
      and control the activity and functionality of bio-molecules. Unconjugated
      bilirubin (UCB), a waste product resulting from heme catabolism, is highly
      sensitive towards blue light induced configurational conversion from (4Z,15Z) to
      (4Z,15E)-bilirubin. UCB has a distinct elongated nanostructure which is readily
      photoswitchable to spherical by external blue light (470 nm) irradiation. Herein,
      the morphology alteration by blue light was nicely correlated with the
      photoisomerisation of UCB, using different microscopic and spectroscopic
      techniques. To restrict the other photo-incidents during phototreatment on UCB, a
      suitable time frame was calibrated by monitoring the absorption, HPLC, lifetime
      distribution and 1H NMR studies. Furthermore, by the help of this morphological
      transition as a marker, UCB early stage photoisomerisation has also been
      triggered by two-photon irradiation (940 nm).

PMID- 30289142
TI  - Sulfur polymer composites as controlled-release fertilisers.
AB  - Sulfur polymer composites were prepared by the reaction of canola oil and
      elemental sulfur in the presence of the NPK fertiliser components ammonium
      sulfate, calcium hydrogen phosphate, and potassium chloride. These composites
      released nutrients in a controlled fashion, resulting in less wasted fertiliser
      and better health for potted tomato plants when compared to free NPK.

PMID- 30289143
TI  - Dual purpose fibre - SERS pH sensing and bacterial analysis.
AB  - The exploitation of fibre based Raman probes has been challenged by often
      complicated fabrication procedures and difficulties in reproducibility. Here, we
      have demonstrated a simple and cost-effective approach for sensing pH through an
      optical fibre, by employing a wax patterned filter paper-based substrate for
      surface enhanced Raman spectroscopy (SERS). Through this method, high
      reproducibility between fibres was achieved. In addition to sensing pH, it was
      possible to extract fluid samples containing P. aeruginosa for further analysis.
      This dual purpose fibre is bronchoscope deployable, and is able to gather
      information about both the host and pathogen, which may lead to an improved
      treatment plan in future in vivo applications.

PMID- 30289144
TI  - A highly hydrolytically stable lanthanide organic framework as a sensitive
      luminescent probe for DBP and chlorpyrifos detection.
AB  - Organic pollutants have attracted increasing attention due to their strong
      persistence and extensive diffusivity. Plasticizers (PAEs) and organophosphorus
      pesticides (OPs), as the vital part of organic pollutants, have made extensive
      damage to the environment with the rapid development of modern agriculture and
      industry. Therefore, we have, for the first time, carried out a quantitative
      analysis of the PAEs and OPs by fluorescence recognition. A series of
      isostructural lanthanide organic frameworks, [Ln(tftpa)1.5(2,2'-bpy)(H2O)] (Ln =
      Gd 1, Eu 2 and Tb 3, H2tftpa = tetrafluoroterephthalic acid), were hydrothermally
      synthesized, of which 3 exhibited excellent hydrolytic resistance to both boiling
      acidic and basic aqueous solutions. Moreover, luminescence investigations show
      that 3 can be used as a highly sensitive and recyclable luminescence sensor for
      the detection of DBP (di-n-butyl phthalate) in simulated seawater and
      chlorpyrifos in ethanol with the detection limits of 2.07 and 0.14 ppb,
      respectively.

PMID- 30289145
TI  - In situ intercalation of Au nanoparticles and magnetic gamma-Fe2O3 in the walls
      of MCM-41 with abundant void defects for highly efficient reduction of 4
      nitrophenol and organic dyes.
AB  - Nowadays, agglomeration and leaching of metal active sites during reaction and
      recycle processes are considered to be a thorny problem for noble metal-based
      catalysts. Therefore, to make improvements, nano-gold was selected as a
      representative research object for many noble metals. In this study, Au
      nanoparticles (NPs) and magnetic gamma-Fe2O3 were intercalated in situ in the
      walls of MCM-41 via a one-pot hydrothermal method, in which the intercalation
      process was preceded by co-condensation of tetraethyl orthosilicate (TEOS) with
      MPTS-Au complexes ((3-mercaptopropyl)-trimethoxysilane (MPTS), HAuCl4.3H2O), and
      a Fe3O4 sol. By the confinement of silica, Au NPs and gamma-Fe2O3 were well
      dispersed in the walls of MCM-41, the sintering and loss of Au NPs was highly
      restricted, and the magnetic property of gamma-Fe2O3 facilitated the recycling of
      Au-based catalysts. Additionally, abundant void defects appeared in MCM-41 by
      assembly of micelles in different sizes and shapes, greatly improving the surface
      area of target catalysts (>1800 m2 g-1), which provided more opportunities for
      contact and collision between reactors and gold active sites, effectively solving
      the problem of mass transportation. As expected, a series FeAu@MCM-41 catalysts
      showed superior catalytic activity in the reduction of 4-nitrophenol (4-NP) and
      organic dyes (MB, RhB, and MO), and these catalysts were recycled five times
      without significant loss of metal species or catalytic activity. This is
      attributed to the confinement effect of the silica walls and the excellent
      magnetic properties of gamma-Fe2O3. This special structure of FeAu@MCM-41
      catalysts provides more insights for designing and fabricating noble metal-based
      catalysts with desirable performances.

PMID- 30289146
TI  - Synthesis of highly rigid phosphine-oxazoline ligands for palladium-catalyzed
      asymmetric allylic alkylation.
AB  - A highly rigid spiro phosphine-oxazoline ligand skeleton with a spirocarbon
      stereogenic center was developed from 7-bromo-1-indanone. The catalytic
      performance of the ligand was demonstrated in palladium-catalyzed asymmetric
      allylic alkylation. Under optimized conditions, high yields (up to 99%) and
      enantioselectivities (up to 99.9% ee) were obtained for reactions of 1,3
      diphenylallyl acetates and symmetrical 1,3-dicarbonyl substrates.

PMID- 30289147
TI  - An integrated microfluidic/microelectrode array for the study of activity
      dependent intracellular dynamics in neuronal networks.
AB  - In the central nervous system, neurons are organized in specific neural networks
      with distinct electrical patterns, input integration capacities, and
      intracellular dynamics. In order to better understand how neurons process
      information, it is crucial to keep the complex organization of brain circuits.
      However, performing subcellular investigations with high spatial and temporal
      resolution in vivo is technically challenging, especially in fine structures,
      such as axonal projections. Here, we present an on-a-chip system that combines a
      microfluidic platform with a dedicated matrix of electrodes to study activity
      dependent dynamics in the physiological context of brain circuits. Because this
      system is compatible with high-resolution video-microscopy, it is possible to
      simultaneously record intracellular dynamics and electrical activity in
      presynaptic axonal projections and in their postsynaptic neuronal targets.
      Similarly, specific patterns of electrical activity can be applied to both
      compartments in order to investigate how intrinsic and network activities
      influence intracellular dynamics. The fluidic isolation of each compartment
      further allows the selective application of drugs at identified sites to study
      activity-dependent synaptic transmission. This integrated
      microfluidic/microelectrode array (microMEA) platform is a valuable tool for
      studying various intracellular and synaptic dynamics in response to neuronal
      activity in a physiologically relevant context that resembles in vivo brain
      circuits.

PMID- 30289148
TI  - A series of new hybrid selenidostannates with metal complexes prepared in alkylol
      amines.
AB  - A series of new hybrid selenidostannates [Mn(en)2(hda)]2[Sn2Se6](1, en =
      ethylenediamine, hda = N-(2-hydroxyethyl)ethylenediamine),
      [Ni(teta)(en)][Ni(teta)(hda)][Sn4Se10] (2, teta = triethylenetetramine),
      [Mn(hda)2]n[SnMnSe4]n (3), [Mn(dien)2]n[SnMnSe4]n (4, dien = diethylenetriamine),
      and [Zn2(en)2(MU4-SnSe4)]n (5) were solvothermally synthesized in hda solvent and
      structurally characterized. 1 is composed of a discrete [Sn2Se6]4- anion and a
      complex [Mn(en)2(hda)]2+ cation as the counterion. 2 contains the
      [Ni(teta)(en)]2+ ion, [Ni(teta)(hda)]2+ ion and [Sn4S10]4- adamantane-like ion
      built from the corner-sharing connection of four [SnSe4]4- tetrahedra, which
      offers the rare example of hybrid selenidostannate combined with two different
      types of transition metal complexes as counterions. Both 3 and 4 contain a 1-D
      heterometallic [SnMnSe42-]n anionic chain constructed from [Sn/MnSe4] tetrahedra
      sharing opposite edges, whose Sn4+ and Mn2+ ions are situated at the same site in
      the lattice, but their chains exhibit two different configurations. 5 exhibits a
      new type of 2-D organic-decorated [Zn2(en)2(MU4-SnSe4)]n layer incorporating rare
      tetrahedral [ZnSe2(en)] complexes. Their optical and photocurrent response
      properties were studied, and density functional theory calculations for 5 were
      also performed.

PMID- 30289149
TI  - APOBEC3B protein expression and mRNA analyses in patients with high-grade serous
      ovarian carcinoma.
AB  - APOBEC3 enzymes are part of the innate immune system and they are important in
      retroviral defense. The number of mutations in ovarian cancer increases with
      rising levels of APOBEC3B mRNA. We could confirm that APOBEC3B mRNA is
      upregulated in ovarian cancer cell lines and in ovarian cancer tissue. We
      evaluated APOBEC3B expression in histologically defined subtypes of ovarian
      cancer to identify its influence on overall survival (OS) and progression-free
      survival (PFS). Tissue microarrays from 219 patients with high-grade serous
      (HGSC), 61 with low-grade serous (LGSC), 62 with endometrioid (EC) and 55 with
      clear cell (CCC) ovarian carcinoma were stained using an antibody against
      APOBEC3B. Real-time quantitative PCR was performed to detect APOBEC3B mRNA levels
      in 274 cases of HGSC, in 11 cases of LGSC, in 47 cases of EC and in 29 cases of
      CCC. Tumor-infiltrating lymphocytes (TILs) have been evaluated in a previous
      project. APOBEC3B staining was cytoplasmic as well as nuclear and both were
      positively correlated (P<0.001). In HGSC a trend was detectable for positive
      cytoplasmic staining as favorable regarding OS (P=0.283) and PFS (P=0.137). High
      levels of APOBEC3B mRNA were associated with prolonged PFS in HGSC in univariate
      analyses (P=0.043) and multivariate analyses (HR 0.55; 95%CI 0.35-0.88; P=0.012).
      APOBEC3B cytoplasmic staining and APOBEC3B mRNA were positively correlated with
      TILs. APOBEC3B in HGSC is related to an active immune infiltrate. However, there
      is no evidence for APOBEC3B as a clinically relevant prognostic biomarker.

PMID- 30289150
TI  - [Evaluation of quality of life, social stigma and treatment adherence in patients
      with epilepsy in the Caceres Healthcare Area: a cross-sectional study].
AB  - INTRODUCTION: Epilepsy is a chronic disease with high prevalence. Its impact in
      the quality of life is influenced by factors like disease characteristics,
      comorbidities, stigma perception and treatment adherence. AIM: To assess the
      quality of life, the social stigma and the treatment adherence of patients with
      epilepsy in our area. PATIENTS AND METHODS: Descriptive, observational and cross
      sectional study. Sociodemographic and clinical data were collected. We analyzed
      data on quality of life (QUOLIE-10), social stigma and treatment adherence
      through different questionnaires. RESULTS: 40 patients were studied. The mean age
      was 42.43 +/- 17.20 years, and the onset of epilepsy was 25.88 +/- 16.81 years.
      55% were women. The score in the quality of life questionnaire was 19.28 +/- 8.03
      points in men and 17.00 +/- 7.69 for women, this difference being not
      significant. There were also no significant differences for social stigma, with a
      mean of 11.50 +/- 13.47 points in men and 6.00 +/- 10.36 points for women (p =
      0.152). According to the treatment adherence questionnaire (Morisky-Green), 70%
      of the patients studied were compliant with the treatment. CONCLUSIONS: Patients
      with epilepsy in our environment have a good quality of life, probably related to
      good treatment adherence and compliance. There is low perceived social stigma but
      people with epilepsy still trend to hide their condition.

PMID- 30289151
TI  - Neonatal hypotonia: is it a diagnostic challenge?
AB  - INTRODUCTION: Hypotonia is a frequent sign of disease in newborns. However, it's
      a nonspecific clinical finding: may be the presentation form of a systemic or
      neurological disease. AIMS: To study the main causes of neonatal hypotonia as
      well as to evaluate the diagnostic accuracy of the anamnesis and physical
      examination of the hypotonic newborn. PATIENTS AND METHODS: A 22-year
      retrospective study of hypotonic neonates admitted to the Neonatal Intensive Care
      Unit was conducted. It was performed an initial blind classification of
      hypotonia's type (central-CH, peripheral-PH or undetermined hypotonia) based on
      the clinical history and the recorded data of physical examination. RESULTS: 91
      infants were included. 42 (46.2%) had prenatal history abnormalities:
      polyhydramnios (28.6%), intrauterine growth restriction (21.4%) and pelvic
      presentation (19.0%). 53 (58.2%) required resuscitation at birth. The main
      associated symptoms were respiratory distress (65.9%), feeding difficulties
      (36.5%) and decreased spontaneous movements (22.4%). The final diagnosis was
      reached in 64 newborns (70.3%): 81.3% with CH, 18.7% with PH. The positive
      predictive value of the initial classification was 97.9% in CH and 66.7% in PH
      group. The mortality rate was 8.8% and it was higher in PH group (58.3% vs 1.3%).
      CONCLUSIONS: Neonatal hypotonia can be associated to an extensive list of
      disorders. A detailed clinical history associated to a careful neurological
      evaluation present a high diagnostic predictive value that should guide the
      etiological investigation.

PMID- 30289152
TI  - Radiotherapy plus temozolomide or PCV in patients with anaplastic
      oligodendroglioma 1p19q codeleted.
AB  - INTRODUCTION: Radiotherapy with procarbazine, lomustine, and vincristine (PCV)
      improves overall survival in patients with anaplastic oligodendroglioma 1p19q
      codeleted. PATIENTS AND METHODS: This retrospective analysis investigated
      outcomes in patients with anaplastic oligodendroglioma 1p19q codeleted compared
      two different protocols (radiotherapy plus temozolomide or PCV). The primary end
      points were overall survival and progression-free survival. Secondary endpoint
      was the radiological response. RESULTS: A total of 48 patients were included.
      Mean age was 43 years (range: 19-66 years), 26 were male (54.1%). Twenty-one
      patients received PCV and 27 temozolomide. The baseline characteristics were not
      difference between the groups. The progression-free survival and overall survival
      in the PCV group were 7.2 and 10.6 years respectively and temozolomide were 6.1
      and 9.2 years, both statistically significant. The radiological response was
      present in 80.9% in PCV arm and 70.2% in temozolomide arm there was not
      statistical differences. The multivariate Cox model showed only the significant
      parameters the use of PCV protocol. The toxicity grade 3 or 4 was present in
      42.8% in PCV arm and 11.1% in temozolomide arm. CONCLUSIONS: The most common
      strategy in the Latin America community is the substitution of the PCV for
      temozolomide. This retrospective study showed superior efficacy of PCV than
      temozolomide. The Latin American community effort must be made to be able to have
      the drugs to available for using as a first line of treatment.

PMID- 30289153
TI  - [The importance of semiology and biochemistry in the diagnostic management of a
      peroxisomal biogenesis disorder].
AB  - INTRODUCTION: Peroxisomal biogenesis disorders are due to mutations in the PEX
      genes, which code for peroxins that are required for peroxisomal biogenesis.
      Clinically, they are expressed as a Zellweger syndrome spectrum, and there is a
      wide phenotypic variety. They are diagnosed biochemically, and confirmation is
      molecular. The aim of this illustrative case is to highlight the importance of
      the clinical features and biochemical testing in the management of a peroxisomal
      disease. CASE REPORT: A 3-year-old boy with neonatal hypotonia, overall
      developmental delay and failure to thrive and a pattern of hypomyelinating
      leukodystrophy in brain resonance. The suspected diagnosis was a disorder
      affecting the biogenesis of the peroxisomes due to having found a variant with an
      uncertain meaning in PEX5. The clinical features, the biochemical studies and
      critical analysis, however, made this diagnosis unlikely. Emphasis is placed on
      the management that must be applied when a Zellweger syndrome spectrum is
      suspected. CONCLUSION: In the case reported here, a peroxisomal biogenesis
      disorder was suspected owing to an exome sequencing which, on being critically
      analysed together with the clinical features and the biochemical findings, made a
      peroxisomal disease very unlikely. In cases of clinical suspicion, backed up by
      neuroimaging, the main diagnostic management must be based on the biochemistry
      analysis. Although confirmation is molecular, these tests must be interpreted
      with caution.

PMID- 30289154
TI  - [Cognitive neurorehabilitation: the foundations and applications of neurologic
      music therapy].
AB  - INTRODUCTION: Music is the result of a perception in the brain involving a number
      of cortical and subcortical areas in both brain hemispheres. Increased knowledge
      about brain plasticity and the numerous neuroimaging studies conducted in recent
      years have made it possible to further our understanding of the processing of
      musical stimuli in the brain. This has led to an interest in analysing and
      studying its application in the non-invasive treatment of certain dysfunctions or
      diseases with the aim of helping to achieve an improved quality of life. AIM: To
      outline the foundations and applications of the musical techniques that are used
      in cognitive neurorehabilitation. DEVELOPMENT: Following an initial summary of
      the processing of musical stimuli in the brain, the study goes on to explain the
      foundations of different techniques, as defined by neurologic music therapy, that
      are used efficaciously in cognitive neurorehabilitation. Sounds, which are the
      raw material of music, maintain a temporality and a sequencing that are a useful
      aid in the formation of temporal patterns of the cognitive functions, and
      constitute an assembly or framework that facilitates the learning of sequential
      information processing, such as memory. CONCLUSIONS: The techniques used in
      neurologic music therapy, which in recent years are being applied for cognitive
      neurorehabilitation, are not invasive and offer promising results that, together
      with further research, should be taken into account to be implemented alongside
      the conventional therapies of cognitive neurorehabilitation and stimulation.

PMID- 30289155
TI  - [VI Jornadas Cientificas del Institut de Neurociencies UAB. Communications].

PMID- 30289156
TI  - [The roots of the word "neuropsychology"].

PMID- 30289157
TI  - [Multiple cranial neuropathy: a case report of three paediatric patients].

PMID- 30289158
TI  - [Isolated myopathy due to the m.8344A>G variant is not unusual and may turn into
      multisystem disease over time].

PMID- 30289159
TI  - Antagonistic recursivities and successive cover-ups: the case of private nuclear
      proliferation.
AB  - "Legal recursivity" is a concept introduced by socio-legal scholars to capture
      the progressive elaboration of transnational rules through policy linkages at the
      international and domestic levels, and the associated jurisdictional expansion of
      international institutions to new policy areas. Recursivity can take many forms,
      and this article introduces the concept of "antagonistic recursivity" to capture
      a dual process of recursive legal innovation and antagonistic obstruction by the
      same policy actors. The article shows how such antagonistic recursivity worked in
      the case of the global fight against private nuclear proliferators after the 2003
      revelations about the reach of the A. Q. Khan network. In the case under study,
      antagonistic recursivities took the form of executive-driven innovation in rule
      making and simultaneous subversion of the same rules by the executive most
      implicated in the new cycle of policy innovation: the United States government.
      This paradox can be explained in the following manner. Antagonistic recursivity,
      the article demonstrates, is likely to emerge when legal rules of global
      governance have already been previously defined in an opaque manner, so as to
      help hegemons follow multiple foreign policy goals: the subversion of the most
      recent policy innovations is then the unfortunate result of attempts to hide
      prior cover-ups rather than a purposeful violation of new rules.

PMID- 30289160
TI  - DNA, reconciliation and social empowerment.

PMID- 30289161
TI  - Long-term neurotoxicity and raynaud's phenomenon in patients treated with
      cisplatin-based chemotherapy for malignant ovarian germ cell tumor.
AB  - INTRODUCTION: The aim was to evaluate "overall neuropathy", defined as peripheral
      paresthesias and Raynaud's phenomenon, in long-term survivors of malignant
      ovarian germ cell tumors (MOGCTs) treated with cisplatin-based chemotherapy
      (CBCT) MATERIAL AND METHODS: Ninety-three MOGCT survivors recorded in Norway in
      1980-2009 (median follow-up: 15 years) were included in this analysis. Forty-nine
      received CBCT (CBCT group) and 44 received other or no chemotherapy (non-CBCT
      group). Applying the scale for chemotherapy-induced neurotoxicity, the prevalence
      of overall neuropathy (i.e., score >1 on a 0 to 3 scale) was compared between the
      two groups. 40 women from the CBCT group also underwent neurophysiological and
      neurological examinations; results from the neurological examination were graded
      according to the National Cancer Institute-Common Terminology Criteria for
      Adverse Effects version 4 (NCI-CTCAE scale v4). These women were then categorized
      into subgroups of low (<=3 cycles of CBCT, n=23) and high CBCT (>=4 cycles of
      CBCT, n=17) RESULTS: Twenty-eight (57%) women from the CBCT group reported
      overall neuropathy, compared to 20 (45%) in the non-CBCT group (p=0.06). Of the
      40 MOGCT survivors in the CBCT group who underwent neurophysiological and
      neurological examinations, 14 (35%) showed NCI-CTCAE grade >=1 signs or symptoms
      of peripheral neuropathy. Pathological findings of NCI-CTCAE grade 2 or 3 signs
      or symptoms were found in four survivors (10%) from the high CBCT subgroup, all
      of whom also showed objective signs of neuropathy CONCLUSIONS: Though about half
      of our MOGCT survivors reported overall neuropathy after CBCT, more severe
      pathological neurological/neurophysiological findings that impacted daily living
      were recorded in only 10% of them. Our observations of a similar prevalence of
      self-reported overall neuropathy in the CBCT and non-CBCT group, combined with
      limited objective neurological findings, warrant further study to increase the
      understanding of the specific patho-physiological pathways of long-term, CBCT
      induced neuropathy.

PMID- 30289162
TI  - Morality in racialized institutions.

PMID- 30289163
TI  - Multi-study Factor Analysis.
AB  - We introduce a novel class of factor analysis methodologies for the joint
      analysis of multiple studies. The goal is to separately identify and estimate 1)
      common factors shared across multiple studies, and 2) study-specific factors. We
      develop an Expectation Conditional-Maximization algorithm for parameter estimates
      and we provide a procedure for choosing the numbers of common and specific
      factors. We present simulations for evaluating the performance of the method and
      we illustrate it by applying it to gene expression data in ovarian cancer. In
      both, we clarify the benefits of a joint analysis compared to the standard factor
      analysis. We have provided a tool to accelerate the pace at which we can combine
      unsupervised analysis across multiple studies, and understand the cross-study
      reproducibility of signal in multivariate data. An R package (MSFA), is
      implemented and is available on GitHub. This article is protected by copyright.
      All rights reserved.

PMID- 30289164
TI  - Plausible folk theories: throwing veils of plausibility over zones of ignorance
      in global governance.
AB  - In an age of expertise, where knowledge ostensibly reigns, global governance not
      infrequently settles for ignorance. To understand this puzzle, this article draws
      upon extensive empirical research on two sites within the global governance of
      finance. One is directed to the suppression of money laundering and combating the
      financing of terrorism by the Financial Action Task Force and International
      Monetary Fund. Another intends to stimulate the supply of otherwise scarce money
      to financial markets through global lawmaking by the UN Commission on
      International Trade Law. In both cases vast enterprises of global regulation and
      lawmaking proceed on weakly founded justificatory rhetorics designated here as
      'plausible folk theories.' Six properties make a folk theory plausible:
      parsimony, face validity, rhetorical compactness, ambiguity, affinity with extant
      beliefs, and unexamined premises and logics. Plausible folk theories offer
      organizational benefits to IOs. They also allow a politics of temporality that
      may shorten temporal horizons, or weaken and eliminate IO accountability.
      Finally, three variants of ignorance contribute to choices by international
      organizations not to get beyond plausible folk theories to justify their
      regulatory and lawmaking initiatives: inadvertent ignorance, willful ignorance,
      and strategic or rational ignorance.

PMID- 30289165
TI  - Decreasing influence of arbitrarily applicable verbal relations of recreational
      gamblers: A randomized controlled trial.
AB  - Twenty-one recreational gamblers were randomly assigned to two groups; one group
      was exposed to a conditional discrimination relational training task to bias
      choice allocation to a black machine presented concurrently with a red machine,
      and the other group underwent the same relational training task immediately
      followed by a defusion procedure, designed to expand upon the relations developed
      in the initial relational task. Both groups completed a simulated slot-machine
      task before and after the relational training task, with or without the defusion
      procedure. Results showed that 9 of 11 participants in the relational training
      only group showed an increased bias toward the black machine, compared to only 4
      of 10 in the relational training plus defusion group; this latter group also
      showed greater matched responding. Results suggest that expanding verbal
      relational networks may reduce the influence of any single verbal relation on
      gambling choice behavior.

PMID- 30289166
TI  - Individual differences in learning and biogenic amine levels influence the
      behavioural division between foraging honeybee scouts and recruits.
AB  - Animals must effectively balance the time they spend exploring the environment
      for new resources and exploiting them. One way that social animals accomplish
      this balance is by allocating these two tasks to different individuals. In
      honeybees, foraging is divided between scouts, which tend to explore the
      landscape for novel resources, and recruits, which tend to exploit these
      resources. Exploring the variation in cognitive and physiological mechanisms of
      foraging behaviour will provide a deeper understanding of how the division of
      labour is regulated in social insect societies. Here, we uncover how honeybee
      foraging behaviour may be shaped by predispositions in performance of latent
      inhibition (LI), which is a form of non-associative learning by which individuals
      learn to ignore familiar information. We compared LI between scouts and recruits,
      hypothesizing that differences in learning would correlate with differences in
      foraging behaviour. Scouts seek out and encounter many new odours while locating
      novel resources, while recruits continuously forage from the same resource, even
      as its quality degrades. We found that scouts show stronger LI than recruits,
      possibly reflecting their need to discriminate forage quality. We also found that
      scouts have significantly elevated tyramine compared to recruits. Furthermore,
      after associative odour training, recruits have significantly diminished
      octopamine in their brains compared to scouts. These results suggest that
      individual variation in learning behaviour shapes the phenotypic behavioural
      differences between different types of honeybee foragers. These differences in
      turn have important consequences for how honeybee colonies interact with their
      environment. Uncovering the proximate mechanisms that influence individual
      variation in foraging behaviour is crucial for understanding the ecological
      context in which societies evolve.

PMID- 30289167
TI  - The Outcome-Representation Learning Model: A Novel Reinforcement Learning Model
      of the Iowa Gambling Task.
AB  - The Iowa Gambling Task (IGT) is widely used to study decision-making within
      healthy and psychiatric populations. However, the complexity of the IGT makes it
      difficult to attribute variation in performance to specific cognitive processes.
      Several cognitive models have been proposed for the IGT in an effort to address
      this problem, but currently no single model shows optimal performance for both
      short- and long-term prediction accuracy and parameter recovery. Here, we propose
      the Outcome-Representation Learning (ORL) model, a novel model that provides the
      best compromise between competing models. We test the performance of the ORL
      model on 393 subjects' data collected across multiple research sites, and we show
      that the ORL reveals distinct patterns of decision-making in substance-using
      populations. Our work highlights the importance of using multiple model
      comparison metrics to make valid inference with cognitive models and sheds light
      on learning mechanisms that play a role in underweighting of rare events.

PMID- 30289168
TI  - Differentiation of self and trait anxiety: A cross-cultural perspective.
AB  - Cultural differences are likely to affect the ability to deal with anxiety. We
      investigated this issue among four cultural groups-Germans and Italians
      (Europeans living in South Tyrol, Italy), Jews and Arabs (Israelis)-in terms of
      their levels of differentiation of self, trait anxiety and somatic symptoms. We
      also examined the relationship of differentiation of self to trait anxiety and
      somatic symptoms. The sample consisted of 824 students: 387 Israelis (mean age
      23.6) and 437 Europeans (mean age 22.3). Israeli participants reported lower
      levels of trait anxiety than European students. Jewish students reported lower
      trait anxiety than Arab students (mean difference = -.14, p < .009), while there
      was no difference between German and Italian students (mean difference = .03, p >
      .99). Jews reported a significantly lower level of emotional cutoff than Arabs
      (mean difference = -.45, p < .001), and Germans reported a significantly lower
      level of emotional reactivity than Italians (mean difference = .29, p < .001).
      Emotional reactivity and I-position predicted all participants' trait anxiety. On
      the whole, results point to the importance of examining differentiation of self
      when trying to reduce trait anxiety, as well as some important cultural
      differences.

PMID- 30289169
TI  - Internalising symptoms and verbal working memory in school-age children: A
      processing efficiency analysis.
AB  - The current study investigated differential contributions of internalising
      symptoms (state anxiety, trait anxiety, depression) to school-age children's
      verbal short-term (STM) and working memory (WM) span accuracy and efficiency
      (microanalysis of response times). Children's (N = 125, Mage  = 11.44 years)
      STM/WM was assessed with simple/complex span tasks. Our analyses revealed that:
      (a) children with high levels of state anxiety displayed reduced simple span
      accuracy (on Word span) and poorer efficiency on both simple (preparatory
      intervals, interword pauses) and complex span (preparatory intervals) response
      time segments; (b) trait anxiety was a negative predictor of children's complex
      span accuracy, as well as their efficiency on both simple (word durations) and
      complex span (interword pauses) response time measures; (3) depressive symptoms
      predicted longer simple span interword pauses. Findings indicate that while all
      internalising symptoms were predictive of children's poorer memory search
      efficiency, especially during the "silent", executive intervals (interword
      pauses), anxiety symptoms were specifically predictive of children's impaired
      span accuracy and other efficiency indicators (preparatory intervals, word
      durations). The study highlights the differential contributions of state, trait
      anxiety, and depressive symptoms to STM/WM in children, emphasising the need to
      measure both accuracy and efficiency to assess the role that such symptoms play
      in children's performance.

PMID- 30289170
TI  - Disentangling the contributions of maternal and fetal factors to estimate
      stillbirth risks for intrapartum adverse events in Tanzania and Uganda.
AB  - OBJECTIVE: To estimate the stillbirth risk associated with intrapartum adverse
      events, controlling for fetal and maternal factors. METHODS: The present study
      was an analysis of cross-sectional patient-record and facility-file data from
      women with viable fetuses who experienced obstetric adverse events at 23
      hospitals and 38 health centers in Tanzania (between December 2015 and October
      2016), and 22 hospitals, 16 level-4 health centers, and five level-3 health
      centers in Uganda (between May 2016 and September 2017). Adverse events were
      categorized in three severity groups (postpartum, intrapartum non-near-miss, and
      intrapartum near-miss) to calculate stillbirth rates and adjusted prevalence
      ratios. RESULTS: Data from 3816 women in Tanzania and 8305 in Uganda were
      included. Compared with postpartum adverse events, intrapartum near-miss was
      associated with a 3.73- and 4.55-fold higher prevalence of stillbirth in Uganda
      and Tanzania, respectively. Most women who experienced near-miss had organ
      dysfunction on arrival or developed it soon after. The risk of stillbirth was
      higher among preterm deliveries compared with term deliveries, and was 42% and
      59% lower in Tanzania and Uganda, respectively, for cesarean deliveries compared
      with vaginal deliveries after intrapartum non-near-miss adverse events.
      CONCLUSION: Stillbirth risk increased with severity of complications and was
      higher among premature deliveries. Survival was higher for cesarean deliveries in
      intrapartum non-near-miss complications, identifying the opportunity to prevent
      deterioration by timely actions.

PMID- 30289171
TI  - Managing tensions in assessment: moving beyond either-or thinking.
AB  - CONTEXT: In health professions education, assessment systems are bound to be rife
      with tensions as they must fulfil formative and summative assessment purposes, be
      efficient and effective, and meet the needs of learners and education institutes,
      as well as those of patients and health care organisations. The way we respond to
      these tensions determines the fate of assessment practices and reform. In this
      study, we argue that traditional 'fix-the-problem' approaches (i.e. either-or
      solutions) are generally inadequate and that we need alternative strategies to
      help us further understand, accept and actually engage with the multiple
      recurring tensions in assessment programmes. METHODS: Drawing from research in
      organisation science and health care, we outline how the Polarity ThinkingTM
      model and its 'both-and' approach offer ways to systematically leverage
      assessment tensions as opportunities to drive improvement, rather than as
      intractable problems. In reviewing the assessment literature, we highlight and
      discuss exemplars of specific assessment polarities and tensions in educational
      settings. Using key concepts and principles of the Polarity ThinkingTM model, and
      two examples of common tensions in assessment design, we describe how the model
      can be applied in a stepwise approach to the management of key polarities in
      assessment. DISCUSSION: Assessment polarities and tensions are likely to surface
      with the continued rise of complexity and change in education and health care
      organisations. With increasing pressures of accountability in times of stretched
      resources, assessment tensions and dilemmas will become more pronounced. We
      propose to add to our repertoire of strategies for managing key dilemmas in
      education and assessment design through the adoption of the polarity framework.
      Its 'both-and' approach may advance our efforts to transform assessment systems
      to meet complex 21st century education, health and health care needs.

PMID- 30289172
TI  - Prolonged exposure to carbon nanoparticles induced methylome remodeling and gene
      expression in zebrafish heart.
AB  - Growing black carbon (BC) emission has become one of the major urgent
      environmental issues facing human beings. Usually, BC or BC-containing carbon
      nanoparticles (CNPs) were recognized as non-directly toxic components of
      atmospheric particulate matter. However, epidemiology studies have provided much
      evidence of the associations of exposure of particulate-containing carbon
      particles with cardiovascular diseases. There are still no related studies to
      support the epidemiological conclusions. Hence, in this article we exposed adult
      zebrafish to CNPs for 60 days, and then explored the heart location and potential
      adverse effects on cardiac tissues of these nanosized carbon particles. Our
      results first showed direct visualization of cardiac endothelial uptake and heart
      deposition of CNPs in zebrafish. In addition, CNPs caused significant
      ultrastructural alterations in myocardial tissue and induced the expression of
      inflammatory cytokines in a dose-dependent manner, resulting in sub-endocardial
      inflammation and cell apoptosis. Moreover, our data demonstrated the
      perturbations caused by CNPs on DNA methylation, suggesting that DNA methylome
      remodeling might play a critical role in CNP-induced cardiotoxicity in zebrafish
      heart. Therefore, this study not only proved a laboratory link between CNP
      exposure and cardiotoxicity in vivo, but also indicated a possible toxicity
      mechanism involved.

PMID- 30289173
TI  - Beta-lactam-induced severe neutropaenia: a descriptive study.
AB  - The objectives of this study were to describe the characteristics and natural
      history of beta-lactam-induced severe neutropaenia and to evaluate the risk of
      recurrences after another beta-lactam readministration. Reports of pure
      agranulocytosis associated with a beta-lactam exposure within the 10 days
      preceding the neutropaenia were extracted from the French Pharmacovigilance
      Database over the year 2010. Cases with another evident cause or more likely
      attributable to another drug were excluded. Data were analyzed for demographics,
      clinical and biological features, prognosis factors, granulocyte colony
      stimulating factors administration and outcome. Sixty-two cases were included
      (median age: 65 years). The median duration of treatment before neutropaenia was
      16 days. In 47% of cases, the diagnosis was made on a systematic blood cell
      count. The median neutrophil count at nadir was 0.125 * 109 /L, and bone marrow
      examination evidenced features of neutrophilic maturation arrest or aplasia in 21
      patients, hyperplasia of granulopoietic cells in three and normal findings in
      five. Three patients developed severe sepsis. All but one recovered a normal
      blood cell count within 2-56 days after beta-lactam discontinuation. The last
      patient died from recurrent severe septic shock. No significant effect of
      granulocyte colony stimulating factor on the mean duration of haematological
      recovery was found. Among the 21 patients who later received another beta-lactam,
      two experienced recurrence of the neutropaenia after receiving a beta-lactam from
      another subfamily. Beta-lactam-induced agranulocytosis was usually observed after
      prolonged treatment, and severe complications are uncommon. In most patients, a
      subsequent treatment with another beta-lactam was well tolerated.

PMID- 30289174
TI  - Knowledge regarding and patterns of genetic testing in patients newly diagnosed
      with breast cancer participating in the iCanDecide trial.
AB  - BACKGROUND: The current study reports rates of knowledge regarding the
      probability of a BRCA1 and/or S pathogenic variant and genetic testing in
      patients with breast cancer, collected as part of a randomized controlled trial
      of a tailored, comprehensive, and interactive decision tool (iCanDecide).
      METHODS: A total of 537 patients newly diagnosed with early-stage breast cancer
      were enrolled at the time of their first visit in 22 surgical practices, and were
      surveyed 5 weeks (496 patients; Response Rate [RR], 92%) after enrollment after
      treatment decision making. Primary outcomes included knowledge regarding the
      probability of carrying a BRCA1 and/or BRCA2 pathogenic variant and genetic
      testing after diagnosis. RESULTS: Overall knowledge regarding the probability of
      having a BRCA1 and/or BRCA2 pathogenic variant was low (29.8%). Significantly
      more patients in the intervention group compared with the control group had
      knowledge regarding the probability of a BRCA1 and/or BRCA2 pathogenic variant
      (35.8% vs 24.4%; P <.006). In multivariable logistic regression, the intervention
      arm remained significantly associated with knowledge regarding the probability of
      having a BRCA1 and/or BRCA2 pathogenic variant (odds ratio, 1.79; 95% confidence
      interval, 1.18-2.70). CONCLUSIONS: The results of the current study suggest that
      although knowledge concerning the probability of having a BRCA1 and/or BRCA2
      pathogenic variant remains low in this patient population, the interactive
      decision tool improved rates compared with a static Web site. As interest in
      genetic testing continues to rise, so will the need to integrate tools into the
      treatment decision process to improve informed decision making.

PMID- 30289175
TI  - The toll like receptor 4-myeloid differentiation factor 88 pathway is essential
      for particulate matter-induced activation of CD4-positive cells.
AB  - Asian sand dust (ASD), a type of particulate matter (PM) found in Asia, can be
      transported to East Asia. We recently found that acute splenic inflammation is
      induced by ASD in mouse models. In this study, we examined the effect of sub
      chronic ASD exposure on mouse immune cells. Mice were intratracheally
      administered ASD once every 2 weeks for 8 weeks and killed 24 hours after the
      final administration. Wild-type (WT) mice showed increased cell viability after
      ASD administration. In contrast, ASD administration induced splenocyte activation
      in toll-like receptor (TLR)2-/- , but not TLR4-/- mice. Furthermore, concanavalin
      A-induced interleukin-2 production increased after ASD administration in WT and
      TLR2-/- mice, but not in TLR4-/- or myeloid differentiation factor (MyD)88-/-
      mice. Immunoblotting demonstrated that nuclear factor kappaB (NF-kappaB) was
      activated in WT mice, but not in TLR4-/- or MyD88-/- mice. The NF-kappaB
      dependent gene products CDK2 and intercellular cell adhesion molecule-1 were
      upregulated upon ASD administration in WT mice, but not in TLR4-/- or MyD88-/-
      mice. Furthermore, the particles themselves, rather than particle constituents,
      activated NF-kappaB in CD4-positive cells through the TLR4 or MyD88 pathway.
      Taken together, these results indicate that particle-induced splenic inflammation
      occurs via TLR4-MyD88 signaling.

PMID- 30289176
TI  - Improved, one-pot synthesis of 6-[18 F]fluorodopamine and quality control testing
      for use in patients with neuroblastoma.
AB  - 6-[18 F]Fluorodopamine ([18 F]F-DA) is taken into cells via the norepinephrine
      transporter (NET). Recent [18 F]F-DA positron emission tomography-computed
      tomography (PET-CT) imaging of adult neuroendocrine tumors shows a dramatic
      improvement in sensitivity over the standard-of-care, meta-iodobenzylguanidine
      (MIBG) single-photon emission computed tomography (SPECT)-CT. A new precursor
      (ALPdopamineTM) allows no-carrier-added synthesis resulting in high-molar
      activity [18 F]F-DA. Automated synthesis of [18 F]F-DA was performed in a single
      reactor using a two-step procedure: 1) fluorination via thermolysis of a
      diaryliodonium salt precursor, followed by 2) acid hydrolysis. Phase transfer
      agents, Kryptofix 222 and two tetraalkylammonium salts, were investigated.
      Optimized synthesis of [18 F]F-DA was achieved in 56 to 60 minutes (26% end of
      synthesis [EOS], nondecay corrected). The product passed all Food and Drug
      Administration (FDA)-required quality control testing for human use. Accumulation
      of [18 F]F-DA in SK-N-BE(2)-C (high NET expression) cells was significantly
      higher than in SH-EP (minimal NET expression) cells (P < 0.0001). ALPdopamine
      provides an effective scaffold for the routine production of [18 F]F-DA for human
      use. Validation of uptake by neuroblastoma (NB) cell lines supports the use of
      [18 F]F-DA for imaging NB patients. A pediatric NB imaging trial using [18 F]F-DA
      PET has been approved (Investigational New Drug application (IND) no. 138638)
      based on the methods reported here. We expect [18 F]F-DA will be localized in NB
      tumors and that high-quality functional images will be obtained within minutes
      after injection.

PMID- 30289177
TI  - An ex vivo bladder model with detrusor smooth muscle removed to analyse
      biologically active mediators released from the suburothelium.
AB  - KEY POINTS: Studies of urothelial cells, bladder sheets or lumens of filled
      bladders have suggested that mediators released from urothelium into
      suburothelium (SubU)/lamina propria (LP) activate mechanisms controlling detrusor
      excitability. None of these approaches, however, has enabled direct assessment of
      availability of mediators at SubU/LP during filling. We developed an ex vivo
      mouse bladder preparation with intact urothelium and SubU/LP but no detrusor,
      which allows direct access to the SubU/LP surface of urothelium during filling.
      Pressure-volume measurements during filling demonstrated that bladder compliance
      is governed primarily by the urothelium. Measurements of purine mediators in this
      preparation demonstrated asymmetrical availability of purines in lumen and
      SubU/LP, suggesting that interpretations based solely on intraluminal
      measurements of mediators may be inaccurate. The preparations are suitable for
      assessments of release, degradation and transport of mediators in SubU/LP during
      bladder filling, and are superior to experimental approaches previously used for
      urothelium research. ABSTRACT: The purpose of this study was to develop a
      decentralized (ex vivo) detrusor smooth muscle (DSM)-denuded mouse bladder
      preparation, a novel model that enables studies on availability of urothelium
      derived mediators at the luminal and anti-luminal aspects of the urothelium
      during filling. Urinary bladders were excised from C57BL6/J mice and the DSM was
      removed by fine-scissor dissection without touching the mucosa. Morphology and
      cell composition of the preparation wall, pressure-volume relationships during
      filling, and fluorescent dye permeability of control, protamine sulfate- and
      lipopolysaccharide-treated denuded bladders were characterized. The preparation
      wall contained intact urothelium and suburothelium (SubU)/lamina propria (LP) and
      lacked the DSM and the serosa. The utility of the model for physiological
      research was validated by measuring release, metabolism and transport of purine
      mediators at SubU/LP and in bladder lumen during filling. We determined
      asymmetrical availability of purines (e.g. ATP, ADP, AMP and adenosine) in lumen
      and at SubU/LP during filling, suggesting differential mechanisms of release,
      degradation and bilateral transurothelial transport of purines during filling.
      Some observations were validated in DSM-denuded bladder of the cynomolgus monkey
      (Macaca fascicularis). The novel model was superior to current models utilized to
      study properties of the urothelium (e.g. cultured urothelial cells, bladder
      mucosa sheets mounted in Ussing chambers or isolated bladder strips in organ
      baths) in that it enabled direct access to the vicinity of SubU/LP during
      authentic bladder filling. The model is particularly suitable for understanding
      local mechanisms of urothelium-DSM connectivity and for broad understanding of
      the role of urothelium in regulating continence and voiding.

PMID- 30289178
TI  - Medicated or not medicated hypnotic substance use: strategies in sleep disorders
      among patients of community pharmacy.
AB  - The principal outcome was to identify which hypnotics substances, medicated
      (benzodiazepines, antihistamine, antidepressant...) or not medicated (herbal
      medicine, homeopathy, melatonin...), were consumed by community pharmacy patients
      who reported taking something for sleep disorder, and which factors can influence
      the consumption of medicated substance rather than nonmedicated substance. Data
      were collected via a network of 73 partner pharmacies around Nantes, France.
      Patients who reported taking a substance to sleep completed a questionnaire that
      collected data relative to the different substances consumed by that person for
      sleep, and the desired effect. Substances were classified in Hypnotic Drug
      Substances and nonmedicated hypnotic substances. A logistical regression was done
      in order to highlight the factors associated with the consumption of Hypnotic
      Drug Substance rather than nonmedicated hypnotic substances. Six hundred and
      forty-seven patients were included, with an average age of 58 years and 74%
      female. The principal strategy employed to combat sleep disorder was the
      consumption of Hypnotic Drug Substance (54%), followed by herbal medicine (32%)
      and homeopathy (19%). The factors positively associated with the consumption of a
      Hypnotic Drug Substance are age, living alone, being out of work, or in the
      process of looking for a job and being a parent. In our survey, the use of
      Hypnotic Drug Substance to help patients with sleep is far from systematic. On
      the other hand, among patients who consume HDS, misuse is still significant,
      particularly in terms of the duration of consumption.

PMID- 30289179
TI  - Peripheral T-cell non-Hodgkin lymphoma manifesting as a primary lesion on the
      lip: A rare case report.
AB  - Primary manifestations of extraganglion non-Hodgkin lymphoma (NHL) from T-cells
      in the oral cavity are rare and often difficult to diagnose. Herein, we describe
      a case of T-cell NHL with a primary lesion on the lip diagnosed with a 25-year
      old woman. The patient reported the appearance of the initial lesion on the upper
      lip, which advanced to the hard palate and oral mucosa. Histological examination
      and immunohistochemistry were compatible with peripheral T-cell NHL without
      further specifications. The proposed treatment consisted of six cycles of
      multiagent chemotherapy. The patient died from complications of the disease
      before the third cycle of chemotherapy. Understanding the clinical signs of
      lymphoma is important for the early diagnosis of this disease to avoid aggressive
      and potentially fatal behavior.

PMID- 30289181
TI  - Is CGRP Receptor Blockade Cardiovascularly Safe? Appropriate Studies Are Needed.

PMID- 30289182
TI  - Choose Wisely: Adapt the Classification Characteristics for "Migraine Trigger
      Points".

PMID- 30289180
TI  - Psychotic experiences are associated with health anxiety and functional somatic
      symptoms in preadolescence.
AB  - BACKGROUND: Health anxiety (HA) is an increasing public health problem related to
      increased health service costs, and associated with functional somatic symptoms
      (FSS) and considerable personal suffering. Abnormal bodily experiences which may
      resemble HA and FSS are common in psychotic disorders, but a potential link
      between HA and psychosis vulnerability in childhood is largely unexplored. The
      current study estimates the association between subclinical psychotic experiences
      (PE) and HA and FSS in a general population cohort of preadolescents. METHODS:
      The study population consisted of 1,572 11-12-year-old children from the
      Copenhagen Child Cohort 2000. PE were comprehensibly assessed as either present
      or not present using the Kiddie Schedule of Affective Disorders and Schizophrenia
      psychosis section. HA and FSS were assessed by self-report on validated
      questionnaires. Additional variables on general psychopathology, puberty, and
      chronic somatic illness were also obtained. RESULTS: Psychotic experiences were
      associated with the top 10% high scores of HA (Odds Ratio (OR) 3.2; 95% CI: 2.1
      4.8) and FSS (OR 4.6; 95% CI: 3.1-6.9) in univariate analyses. After mutual
      adjustment, the association was reduced to (HA: OR 2.3; 95% CI: 1.5-3.5; FSS: OR
      3.7; 95% CI: 2.4-4.7), suggesting interdependence. Further adjustment for
      potential confounders and general psychopathology only reduced the associations
      slightly: HA OR 2.2 (95% CI: 1.4-3.4); FSS OR 3.3 (95% CI: 2.1-5.2). Secondary
      analyses of subdimensions of HA showed that PE were associated with fears (OR
      3.0; 95% CI: 2.0-4.6) and daily impact of HA symptoms (OR 5.0; 95% CI: 3.4-7.5),
      but not help seeking (OR 1.2; 95% CI: 0.7-2.1). CONCLUSIONS: This is the first
      study to investigate the associations between PE and HA and FSS, respectively. PE
      were significantly associated with HA and FSS over and above general
      psychopathology in preadolescence. Individuals with PE expressed high levels of
      health-related fears and daily impact, but no corresponding help-seeking
      behavior.

PMID- 30289183
TI  - The Importance of Statistical Power Calculations.

PMID- 30289184
TI  - Molecular receptors for recognition and sensing of nucleotides.
AB  - Nucleotides have a variety of functions in cellular metabolism and they are the
      constitutes of nucleic acids. Synthetic receptors and sensors are required to
      reveal the role of nucleotides in living organisms and mechanisms of signal
      transduction events. In recent years, a large number of nucleotide-selective
      synthetic receptors have been devised that utilize different molecular designs
      and sensing mechanisms. This Minireview presents a recent progress in the design
      of synthetic molecular receptors for selective recognition of nucleotides in
      aqueous solution. The binding properties of receptors and the origins of their
      selectivity for a particular nucleotide are discussed.

PMID- 30289185
TI  - Primary hyperparathyroidism: should surgery be performed on all patients? Current
      evidence and residual uncertainties.
AB  - Primary hyperparathyroidism (pHPT) is the third most common endocrine disease and
      is characterized by hypercalcaemia and elevated or inappropriately 'normal'
      levels of the parathyroid hormone (PTH). The main target organs of PTH are the
      skeletal system and the kidneys. Before the 1970s, pHPT was a rarely detected
      disease associated with notable morbidity and premature mortality. Introduction
      of biochemical screening, allowing for a wide range of indications, has
      contributed to the detection of the full spectrum of the disease. A new entity
      with an isolated elevation of PTH, normocalcaemic HP, has emerged and is
      currently being explored. The highest incidence of pHPT, 3-5%, is observed
      amongst women, and the prevalence increases with age. The female-to-male ratio is
      3-4 : 1 except in younger patients where distribution is equal and known
      hereditary causes account for approximately 10% of the cases. In the last few
      decades, it has become evident that fewer patients than previously believed are
      truly asymptomatic. The cause of pHPT is often a benign tumour, a parathyroid
      adenoma, and the only definite treatment is parathyroidectomy (PTX). No medical
      treatment, single or combined, can achieve a curing of pHPT. Recent data indicate
      that PTX, despite being proven to be cost-effective compared to conservative
      treatment, is underutilized, especially in elderly pHPT patients. The decision of
      PTX should always be based on a safe diagnosis, and the potential benefits of
      curative treatment should not be outweighed by the risks of surgery or
      anaesthesia.

PMID- 30289186
TI  - Superselective endovascular tissue access using trans-vessel wall technique:
      feasibility study for treatment applications in heart, pancreas and kidney in
      swine.
AB  - OBJECTIVES: With the emergence of targeted cell transplantation and gene therapy,
      there is a need for minimally invasive tissue access to facilitate delivery of
      therapeutic substrate. The objective of this study was to demonstrate the
      suitability of an endovascular device which is able to directly access tissue and
      deliver therapeutic agent to the heart, kidney and pancreas without need to seal
      the penetration site. METHODS: In vivo experiments were performed in 30 swine,
      including subgroups with follow-up to evaluate complications. The previously
      described trans-vessel wall (VW) device was modified to be sharper and not
      require tip detachment to seal the VW. Injections into targets in the heart (n =
      13, 24-h follow-up n = 5, 72-h follow-up n = 3), kidney (n = 8, 14-day follow-up
      n = 3) and pancreas (n = 5) were performed. Some animals were used for multiple
      organ injections. Follow-up consisted of clinical monitoring, angiography and
      necropsy. Transvenous (in heart) and transarterial approaches (in heart, kidney
      and pancreas) were used. Injections were targeted towards the subepicardium,
      endomyocardium, pancreas head and tail, and kidney subcapsular space and cortex.
      RESULTS: Injections were successful in target organs, visualized by
      intraparenchymal contrast on fluoroscopy and by necropsy. No serious
      complications (defined as heart failure or persistent arrhythmia, haemorrhage
      requiring treatment or acute kidney injury) were encountered over a total of 157
      injections. CONCLUSIONS: The trans-VW device can achieve superselective
      injections to the heart, pancreas and kidney for delivery of therapeutic
      substances without tip detachment. All parts of these organs including the
      subepicardium, pancreas tail and renal subcapsular space can be efficiently
      reached.

PMID- 30289187
TI  - Urine drug screening for early detection of unwitting use of fentanyl and its
      analogues among people who inject heroin in Sydney, Australia.
AB  - INTRODUCTION AND AIMS: North America has witnessed a dramatic rise in fatal
      opioid overdoses due to the unwitting consumption of non-pharmaceutical fentanyl
      and its analogues. While some of the drivers of this crisis-including
      profitability and access to high-potency opioids through internet sources-also
      apply in Australia, to our knowledge, there have been no ongoing surveillance
      studies of local populations. Therefore, this pilot study aimed to detect
      unintentional fentanyl consumption among people who inject heroin through instant
      urine screening, and determine the feasibility and acceptability of voluntary
      urinalysis of clients at the Medically Supervised Injecting Centre, Kings Cross,
      Sydney. DESIGN AND METHODS: Brief surveys and urine drug screens were conducted
      with 67 participants in Wave 1 (October 2017) and 51 participants in Wave 2
      (March 2018). Urine samples were tested with BTNX Rapid ResponseTM fentanyl urine
      strip test at a detection level of 20 ng/mL norfentanyl. These strips also cross
      react to numerous fentanyl analogues. RESULTS: There were no cases where positive
      urine tests suggested unwitting fentanyl use detected in this study. DISCUSSION
      AND CONCLUSIONS: These negative findings contrast sharply with similar Canadian
      studies. While no cases of fentanyl-laced heroin use have been detected so far,
      we have demonstrated that this surveillance design is low-cost, feasible and
      scalable approach to monitoring the considerable public-health threat of
      undetected fentanyl and its analogues in Australia. Further validation of cross
      reactivity of test strips would strengthen this method.

PMID- 30289188
TI  - Effect of hemodialysis on respiratory mechanics in acute kidney injury patients.
AB  - INTRODUCTION: Hemodialysis (HD) is one treatment for acute kidney injury (AKI)
      patients. Studies have shown that this dialysis modality may lead to changes in
      pulmonary function with an impact on prognosis. The aim of our study was to
      evaluate changes in respiratory mechanics and oxygenation of AKI patients
      admitted to an intensive care unit who were undergoing intermittent mechanical
      ventilation (IMV) and daily HD. METHODS: This prospective cohort study evaluated
      94 AKI patients and 234 HD sessions. Pulmonary static compliance (Pcs),
      resistance (Rsr), and arterial partial pressure of oxygen and the fraction of
      inspired oxygen (PaO2 /FiO2 ) ratio were assessed during the initial three-day
      period of daily HD therapy. FINDINGS: Psc increased progressively during HD
      sessions, from 39.4 +/- 21.4 mL/cm H2 O prior to the initial dialysis to 55.5 +/-
      25.2 at the end of the last dialysis during the study period (P = 0.04).
      Similarly, Rsr and PaO2 /FiO2 ratio also improved, from 11.1 +/- 6.3 cm H2 O/L/s
      prior to the initial dialysis to 8.8 +/- 4.2 at the end of the last dialysis (P
      =0.0027) and from 228 +/- 85 prior to the initial dialysis to 312.1 +/- 111.5, P
      < 0.001, to the end of the last dialysis, respectively. CONCLUSION: This study
      showed that AKI patients undergoing IMV and daily HD improve their respiratory
      mechanics and oxygenation.

PMID- 30289189
TI  - Moving between ideologies in self-management support-A qualitative study.
AB  - BACKGROUND: Reforms in current health policy explicitly endorse health promotion
      through group-based self-management support for people with long-term conditions.
      Health promotion and traditional medicine are based on different logics.
      Accordingly, health professionals in health-promoting settings demand the
      adoption of new practices and ways of thinking. OBJECTIVES: The objective of our
      study was to investigate how health professionals perceive the health-promoting
      group-based self-management support that is politically initiated for people with
      long-term conditions. DESIGN: This study had a qualitative research design that
      included focus group interviews and was guided by a social constructivist
      paradigm in which group-based self-management was viewed as a social
      construction. Different logics at play were analysed through the theoretical lens
      of institutional logic. Discussions among participants show frames of references
      seen as logics. SETTING AND PARTICIPANTS: We recruited health professionals from
      group-based health-promoting measures for people with type 2 diabetes in Norway.
      Two focus groups comprising four and six participants each were invited to
      discuss the practices and value of health promotion through group-based self
      management support. RESULTS: The analysis resulted in three themes of discussion
      among participants that contained reflections of logics in movement. Health
      professionals' discussions moved between different logics based on the importance
      of expert-based knowledge on compliance and on individual lifestyle choices.
      DISCUSSION AND CONCLUSION: The study indicates that health promotion through self
      management support is still a field "in the making" and that professionals strive
      to establish new logics and practices that are not considered difficult to manage
      or do not contain incompatible understandings.

PMID- 30289190
TI  - Association between pain-related fear and presenteeism among eldercare workers
      with low back pain.
AB  - BACKGROUND: Presenteeism (work productivity loss at work) and low back pain (LBP)
      are prevalent among eldercare workers. Presenteeism is a serious emerging problem
      in an occupational setting. While many studies report the impact of pain-related
      fear on absenteeism, its impact on presenteeism remains unclear. METHODS: We
      conducted a cross-sectional study to investigate the association between pain
      related fear and presenteeism among 505 eldercare workers with LBP. We measured
      pain-related fear using the 11-item Tampa Scale for Kinesiophobia (TSK-11). We
      used the Work Limitations Questionnaire (WLQ) to estimate productivity loss due
      to presenteeism with items including Time Management, Mental-Interpersonal
      Demands, Physical Demands, and Output Demands. The presenteeism was categorized
      into no (<5%), mild (5%-10.9%), moderate (11%-16.9%), and severe presenteeism
      (>=17%). We further performed ordinal logistic regression analyses, and the
      covariates were age, sex, pain intensity, pain disability, and psychosocial
      factors. Multiple imputation was conducted to provide informed estimates for
      observations with missing data. RESULTS: After adjustment, a higher TSK score was
      significantly associated with a higher presenteeism (proportional OR = 1.10, 95%
      CI = 1.06-1.15). A significant association of TSK with all WLQ subscales was
      retained even after the adjustment (Time Management: proportional OR = 1.04, 95%
      CI = 1.01-1.08; Mental-Interpersonal Demands: proportional OR = 1.08, 95% CI =
      1.04-1.12; Physical Demands: proportional OR = 1.04, 95% CI = 1.01-1.08; and
      Output Demands: proportional OR = 1.06, 95% CI = 1.02-1.10). CONCLUSIONS: Our
      findings suggest that pain-related fear is an important factor related to
      presenteeism among eldercare workers with LBP. This article is protected by
      copyright. All rights reserved.

PMID- 30289191
TI  - Neutral mechanisms and niche differentiation in steady-state insular microbial
      communities revealed by single cell analysis.
AB  - In completely insular microbial communities, evolution of community structure
      cannot be shaped by the immigration of new members. In addition, when those
      communities are run in steady state, the influence of environmental factors on
      their assembly is reduced. Therefore, one would expect similar community
      structures under steady-state conditions. Yet, in parallel setups, variability
      does occur. To reveal ecological mechanisms behind this phenomenon, five parallel
      reactors were studied at the single-cell level for about 100 generations and
      community structure variations were quantified by ecological measures. Whether
      community variability can be controlled was tested by implementing soft
      temperature stressors as potential synchronizers. The low slope of the lognormal
      rank-order abundance curves indicated a predominance of neutral mechanisms, i.e.,
      where species identity plays no role. Variations in abundance ranks of
      subcommunities and increase in inter-community pairwise beta-diversity over time
      support this. Niche differentiation was also observed, as indicated by steeper
      geometric-like rank-order abundance curves and increased numbers of correlations
      between abiotic and biotic parameters during initial adaptation and after
      disturbances. Still, neutral forces dominated community assembly. Our findings
      suggest that complex microbial communities in insular steady-state environments
      can be difficult to synchronize and maintained in their original or desired
      structure, as they are non-equilibrium systems.

PMID- 30289192
TI  - Factors affecting TST level in patients undergoing dialysis: a multicenter study.
AB  - INTRODUCTION: The risk of TB is increased in patients with chronic kidney disease
      (CKD) when compared with individuals with normal renal function. We aimed to
      determine tuberculin skin test (TST) response and the factors which might affect
      the response in patients with CKD undergoing dialysis in this study. METHODS: The
      purified protein derivative solution was administered to the patients and the
      diameter of induration was measured. Additionally, the age, gender and smoking
      status of the patients were interrogated. Comorbidities were recorded both by
      patients' self-reports and data from the hospital files. The number of Bacille
      Calmette-Guerin (BCG) scars was recorded by checking both shoulders. FINDINGS:
      The study was conducted with a total of 371 patients (194 men and 177 women). The
      mean age was 60.09 +/- 15.88, TST was 6.99 +/- 6.9, duration of dialysis was 4.44
      +/- 4.5 (3.8-0.1,24). A total of 229 patients have comorbodities (61.7%, the most
      frequent was hypertension). Logistic regression model was performed. Gender,
      vitamin D treatment and high parathormone (PTH) levels remained in the final
      stage of the analysis and vitamin D intake and PTH levels were detected to be
      statistically significant (P = 0.002, 0.007, respectively). DISCUSSION: This
      study is the first study which showed a correlation between TST negativity and
      increased PTH levels and receiving vitamin D treatment. Starting from this point,
      it was concluded that PTH may suppress the immune system and especially cellular
      immunity.

PMID- 30289193
TI  - Mycoviruses mediate mycotoxin regulation in Aspergillus ochraceus.
AB  - To date, no demonstration of a direct correlation between the presence of
      mycoviruses and the quantitative or qualitative modulation of mycotoxins has been
      shown. In our study, we transfected a virus-free ochratoxin A (OTA)-producing
      isolate of Aspergillus ochraceus with purified mycoviruses from a different A.
      ochraceus isolate and from Penicillium aurantiogriseum. Among the mycoviruses
      tested, only Aspergillus ochraceus virus (AoV), a partitivirus widespread in A.
      ochraceus, caused a specific interaction that led to an overproduction of OTA,
      which is regulated by the European Commission and is the second most important
      contaminant of food and feed commodities. Gene expression analysis failed to
      reveal a specific viral upregulation of the mRNA of genes considered to play a
      role in the OTA biosynthetic pathway. Furthermore, AoOTApks1, a polyketide
      synthase gene considered essential for OTA production, is surprisingly absent in
      the genome of our OTA-producing isolate. The possible biological and evolutionary
      implications of the mycoviral regulation of mycotoxin production are discussed.

PMID- 30289194
TI  - Migration of retrobulbar wooden foreign body between diagnostic imaging and
      surgical extraction in a German shepherd dog.
AB  - A 2-year-old, male castrated German shepherd dog was presented to the University
      of Tennessee Veterinary Medical Center (UTVMC) with periorbital swelling and
      conjunctival mucopurulent discharge 2 days following removal of a twig from the
      medial canthus by the owner. Diagnostic imaging was pursued due to the suspicion
      of a retrobulbar foreign body (FB). A cylindrical FB approximately 3.0 cm in
      length and 1.0 cm in diameter with concentric rings, suspected to be wooden
      material, was identified on computed tomography (CT) imaging. An attempt to
      remove the FB via a stab incision using ultrasound guidance was unsuccessful, and
      postmanipulation ultrasound confirmed the FB position was unchanged. An
      exploratory orbitotomy was performed, using the acquired CT images for guidance
      in locating the FB; however, the FB was not present at the predicted site. The CT
      imaging was repeated and showed that the FB had migrated rostrally approximately
      3.0 cm, compared to the originally acquired study and its same location during
      attempted ultrasound-guided removal. A combination of CT-guided needle placement
      and contrast injection was then used with repeat imaging in an attempt to better
      localize the FB and its soft tissue tract. The dog was taken back into the
      operating room, and the wooden FB was successfully removed.

PMID- 30289195
TI  - Prospective monitoring of after-hours nursing and technologist support calls to a
      regional Canadian home hemodialysis program.
AB  - INTRODUCTION: Increasing renal care providers offer home hemodialysis (HD) as a
      modality choice. There is considerable variation in the provision of after-hours
      on-call support for self-dialyzing patients and no literature describing the
      utility of this service. In this prospective, observational study we sought to
      monitor and classify the number and nature of interactions between home patients
      and our on-call nurses and technologists, and enumerate the number of adverse
      events averted by the availability of on-call staff. METHODS: Our home HD unit
      provided 24-hour on-call patient support and during a 4-month period in 2012, we
      prospectively monitored all patient calls to this service. The nature of the
      calls was logged as nursing-related vs. technical. Call outcomes were classified
      according to whether patients were able to initiate/resume their treatments or
      whether additional interventions were required. FINDINGS: During this period, our
      program cared for 58 home HD patients. Nurses fielded 172 calls and dealt with
      239 issues. One hundred nine (46%) were clinical issues including 5 (2%) of a
      serious nature involving potential harm; 67 (28%) related to machine setup or
      alarms, 36 (15%) required a technologist to resolve, and 27 (11%) were deemed non
      urgent. One hundred six issues were directed to technologists in 99 calls. Issues
      pertained to machine malfunction (45 calls-43%), machine set-up and alarms (25
      calls-24%), or the water system (24 calls-23%). Only 12 calls (11.3%) were not of
      a technical nature. Nursing and technologist support allowed patients to initiate
      or continue their treatment 75% and 71% of the time, respectively. DISCUSSION:
      Home HD on-call services provide patients support to successfully continue their
      dialysis treatments by troubleshooting clinical and technical aspects of dialysis
      and by averting potential adverse events.

PMID- 30289196
TI  - Psychological distress, role, and identity changes in mothers following a
      diagnosis of cancer: A systematic review.
AB  - OBJECTIVE: To systematically review findings of the impact of cancer diagnosis
      and treatment on mothers' psychological well-being, roles, and identity and to
      explore the psychosocial factors that contribute to mothers' psychological well
      being. METHODS: Six databases were searched for research articles and theses
      exploring the association between the impact of cancer diagnosis and treatment on
      mothers' psychological well-being, identity, and role, and the psychosocial
      factors contributing to mothers' psychological distress regardless of their
      cancer type and stage. The Mixed-Method Appraisal Bias Tool was used to assess
      the selected studies' methodological quality. RESULTS: A total of 30 qualitative,
      quantitative, and mixed-method studies were deemed eligible for inclusion. Most
      studies reported that mothers experienced significant psychological distress,
      changes to or loss of parenting efficacy, maternal identity, and role.
      Psychosocial factors that contributed to mothers' distress included mothers'
      young age, presence of metastases, lower parenting efficacy, fear of cancer
      recurrence, higher illness intrusiveness, and lack of appropriate support. Four
      main themes emerged from the qualitative studies: psychological impact of cancer
      on mothers, changes in maternal identity and role, relationship changes and
      concerns for their children, and meaning-making in cancer experience.
      CONCLUSIONS: Changes in mothers' psychological well-being, role, and identity
      occurred across cancer diagnoses, treatment, and recovery trajectories. The
      evidence suggests that mothers may benefit from continued and tailored
      psychosocial support to cope with these challenges, even after treatment is
      completed. Further studies with improved methodological quality are needed to
      explore these issues in depth.

PMID- 30289197
TI  - Iron- and aluminium-induced depletion of molybdenum in acidic environments
      impedes the nitrogen cycle.
AB  - Anthropogenic nitrate contamination is a serious problem in many natural
      environments. Nitrate removal by microbial action is dependent on the metal
      molybdenum (Mo), which is required by nitrate reductase for denitrification and
      dissimilatory nitrate reduction to ammonium. The soluble form of Mo, molybdate
      (MoO4 2- ), is incorporated into and adsorbed by iron (Fe) and aluminium (Al)
      (oxy) hydroxide minerals. Herein we used Oak Ridge Reservation (ORR) as a model
      nitrate-contaminated acidic environment to investigate whether the formation of
      Fe- and Al-precipitates could impede microbial nitrate removal by depleting Mo.
      We demonstrate that Fe and Al mineral formation that occurs as the pH of acidic
      synthetic groundwater is increased, decreases soluble Mo to low picomolar
      concentrations, a process proposed to mimic environmental diffusion of acidic
      contaminated groundwater. Analysis of ORR sediments revealed recalcitrant Mo in
      the contaminated core that co-occurred with Fe and Al, consistent with Mo
      scavenging by Fe/Al precipitates. Nitrate removal by ORR isolate Pseudomonas
      fluorescens N2A2 is virtually abolished by Fe/Al precipitate-induced Mo
      depletion. The depletion of naturally occurring Mo in nitrate- and Fe/Al
      contaminated acidic environments like ORR or acid mine drainage sites has the
      potential to impede microbial-based nitrate reduction thereby extending the
      duration of nitrate in the environment.

PMID- 30289198
TI  - Long-term efficacy of novel therapies in moderate-to-severe plaque psoriasis: a
      systematic review and network meta-analysis of PASI response.
AB  - BACKGROUND: Patients with moderate-to-severe psoriasis require long-term
      treatment, yet few trials compare outcomes beyond a short-term induction period.
      Quantitative comparisons of long-term outcomes in patients with psoriasis are
      limited. To our knowledge, no network meta-analysis (NMA) of such data has been
      performed. OBJECTIVE: To compare novel systemic therapies, both biologic and non
      biologic, approved for moderate-to-severe psoriasis by conducting a systematic
      review (SR) and NMA of Psoriasis Area and Severity Index (PASI) outcomes measured
      at or around 1 year. METHODS: An SR was conducted to identify studies reporting
      PASI 75, PASI 90 and PASI 100 responses. Feasibility of an NMA on maintenance
      phase endpoints was assessed and sources of heterogeneity considered. Data
      appropriate for analysis were modelled using a Bayesian multinomial likelihood
      model with probit link. Wherever possible, data corresponding to an intention-to
      treat approach with non-responder imputation were used. RESULTS: Twenty-four
      studies reporting outcomes at 40-64 weeks were identified, but heterogeneity in
      study design allowed synthesis of only 17. Four 52-week randomized controlled
      trials (RCTs) comprised the primary analysis, which found brodalumab was
      significantly more efficacious than secukinumab, ustekinumab and etanercept.
      Secukinumab was also more efficacious than ustekinumab and both outperformed
      etanercept. In a secondary analysis, evidence from 13 additional studies and 4
      further therapies (adalimumab, apremilast, infliximab and ixekizumab) was
      included by comparing long-term outcomes from active interventions to placebo
      outcomes extrapolated from induction. Results were consistent with the primary
      analysis: brodalumab was most effective, followed by ixekizumab and secukinumab,
      then ustekinumab, infliximab and adalimumab. Etanercept and apremilast had the
      lowest expected long-term efficacy. Results were similar when studies with low
      prior exposure to biological therapies were excluded. CONCLUSION: Results suggest
      that brodalumab is associated with a higher likelihood of sustained PASI
      response, including complete clearance, at week 52 than comparators. Further long
      term active-comparator RCT data are required to better assess relative efficacy
      across therapies.

PMID- 30289199
TI  - Neuropathy and inflammation in diabetic bone marrow.
AB  - Diabetes impairs the bone marrow (BM) architecture and function as well as the
      mobilization of immature cells into the bloodstream and number of potential
      regenerative cells. Circadian regulation of bone immature cell migration is
      regulated by beta-adrenergic receptors, which are expressed on haematopoietic
      stem cells, mesenchymal stem cells, and osteoblasts in the BM. Diabetes is
      associated with a substantially lower number of sympathetic nerve terminal
      endings in the BM; thus, diabetic neuropathy plays a critical role in BM
      dysfunction. Treatment with mesenchymal stem cells, BM mononuclear cells,
      haematopoietic stem cells, and stromal cells ameliorates the dysfunction of
      diabetic neuropathy, which occurs, in part, through secreted neurotrophic
      factors, growth factors, adipokines, and polarizing macrophage M2 cells and
      inhibiting inflammation. Inflammation may be a therapeutic target for BM stem
      cells to improve diabetic neuropathy. Given that angiogenic and neurotrophic
      effects are two major barriers to effective diabetic neuropathy therapy,
      targeting BM stem cells may provide a novel approach to develop these types of
      treatments.

PMID- 30289200
TI  - Clinical characteristics and risk factors for stent-stone complex formation
      following biliary plastic stent placement in patients with common bile duct
      stones.
AB  - BACKGROUND: Stent-stone complex (SSC) formation is one of the complications of
      endoscopic biliary stent placement. This study aimed to clarify the clinical
      characteristics and risk factors for SSC formation following plastic stent (PS)
      placement in patients with common bile duct (CBD) stones. METHODS: We
      retrospectively reviewed the charts of 78 patients with CBD stones who had
      undergone 107 biliary stent placements as palliative treatment. Demographic,
      historical, and stent-related data were collected and analyzed. RESULTS: At PS
      removal, SSC formations were observed in 18% of the 107 cases (SSC group) studied
      and not in the remaining 82% (non-SSC group). The duration of PS placement was
      significantly longer in the SSC group. The increase in CBD diameter during the
      stenting period as well as the incidence of cholangitis at PS removal was
      significantly greater in the SSC group. Multivariate analysis identified long
      term (>=301 days) PS placement and the increase in CBD diameter during the
      stenting period as independent factors for SSC formation. CONCLUSIONS: Long-term
      PS placement induces a risk of SSC formation in patients with CBD stones. The
      increase in diameter of CBD during the period of PS placement is a predictive
      factor for SSC formation in this situation.

PMID- 30289201
TI  - New tools for high-throughput expression of fungal secretory proteins in
      Saccharomyces cerevisiae and Pichia pastoris.
AB  - Heterologous protein expression in yeast, mostly in Saccharomyces cerevisiae and
      Pichia pastoris, is a well-established and widely used technique. It typically
      requires the construction of an expression vector in Escherichia coli containing
      the foreign gene and its subsequent transformation into yeast. Although simple,
      this procedure has important limitations for the expression of large numbers of
      proteins, that is, for the generation of protein libraries. We describe here the
      development of a novel system for the easy and fast expression of heterologous
      proteins both in S. cerevisiae and in P. pastoris, under the control of the GAL1
      and AOX1 promoters respectively. Expression in S. cerevisiae requires only the
      transformation of yeast cells with an unpurified PCR product carrying the gene to
      be expressed, and the expression of the same gene in P. pastoris requires only
      the isolation of the plasmid generated in S. cerevisiae and its transformation
      into this second yeast, thus making this system suitable for high-throughput
      projects. The system has been tested by the extracellular expression of 30
      secretory fungal proteins.

PMID- 30289202
TI  - How Does Oocyte Uptake Occur? A Macroscopic Study of the Ovarian and Oviductal
      Modifications for Egg Capture in the Coral-Snake Micrurus corallinus.
AB  - The processes of follicular development, ovulation, egg capture, and egg
      transport vary among vertebrates. Therefore, analysis of the reproductive tract
      of several lineages is needed for understanding the evolutionary changes of the
      reproductive system. In turtles, the ovulated eggs are released into the coelomic
      cavity and taken up by one of the two oviducts, a phenomenon called extrauterine
      migration of eggs. However, the process of egg uptake in lizards is different.
      The egg is ovulated directly into the infundibulum, and oocyte uptake by the
      contralateral oviduct rarely occurs. The same pattern has been hypothesized to
      occur in snakes. To test this hypothesis, we analyzed the reproductive tract of
      female Micrurus corallinus preserved in zoological collections. We examined the
      anatomical characteristics of the infundibulum and ovary and compared the
      reproductive output between the ovaries to verify the mechanism of egg capture
      and the anatomical viability of extrauterine migration of eggs. The reproductive
      output of the right ovary was higher than that of the left ovary, and the higher
      number of eggs in the right oviduct is due exclusively to the production of the
      ipsilateral ovary. Several anatomical features prevent extrauterine migration of
      eggs, including the asymmetry of the reproductive system, the arrangement of the
      ovarian follicles in a single row, and the formation of a wrapping around the
      ovary and infundibulum by the visceral pleuroperitoneum membrane (preventing
      against ectopic eggs). Therefore, the hypothesis of egg capture by the
      contralateral oviduct is anatomically infeasible in M. corallinus and possibly in
      other snakes. Anat Rec, 301:1936-1943, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30289203
TI  - A Novel Mouse Model for Cilia-Associated Cardiovascular Anomalies with a High
      Penetrance of Total Anomalous Pulmonary Venous Return.
AB  - Primary cilia are small organelles projecting from the cell surface of many cell
      types. They play a crucial role in the regulation of various signaling pathway.
      In this study, we investigated the importance of cilia for heart development by
      conditionally deleting intraflagellar transport protein Ift88 using the col3.6
      cre mouse. Analysis of col3.6;Ift88 offspring showed a wide spectrum of
      cardiovascular defects including double outlet right ventricle and
      atrioventricular septal defects. In addition, we found that in the majority of
      specimens the pulmonary veins did not properly connect to the developing left
      atrium. The abnormal connections found resemble those seen in patients with total
      anomalous pulmonary venous return. Analysis of mutant hearts at early stages of
      development revealed abnormal development of the dorsal mesocardium, a second
      heart field-derived structure at the venous pole intrinsically related to the
      development of the pulmonary veins. Data presented support a crucial role for
      primary cilia in outflow tract development and atrioventricular septation and
      their significance for the formation of the second heart field-derived tissues at
      the venous pole including the dorsal mesocardium. Furthermore, the results of
      this study indicate that proper formation of the dorsal mesocardium is critically
      important for the development of the pulmonary veins. Anat Rec, 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 30289205
TI  - Special Issue on eHealth Innovations and Psycho-Oncology.

PMID- 30289204
TI  - Considerations for Measurement of Embryonic Organ Growth.
AB  - Organogenesis is a complex coordinated process of cell proliferation, growth,
      migration, and apoptosis. Differential growth rates, particularly during
      cardiogenesis, play a role in establishing morphology. Studies using
      stereological and cell sorting methods derive averages of morphogenetic
      parameters for an organ. To understand tissue composition and differential
      growth, the researcher must determine a number of morphogenetic parameters in the
      developing organ. Such measurements require sectioning to enable identification
      of organ borders, tissue components and cell types, three-dimensional (3D)
      reconstruction of sections to visualize morphology and a 3D-measurement scheme to
      build local morphogenetic information. Although thick the section confocal
      microscopy partially solves these issues, information loss at the section surface
      hampers the reconstruction of 3D morphology. Episcopic imaging provides the
      correct morphology but lacks histological procedures to identify multiple cell
      types. The 3D-measurement scheme is based on systematic sampling, with
      overlapping sample volumes, of the entire organ in the aligned image stack. For
      each sample volume, morphogenetic variables are calculated and results projected
      back to the cube (boxel) at the sample volume center. Boxel size determines
      spatial resolution of the final quantitative 3D-reconstruction whereas size of
      the sample volume determines the precision of the morphogenetic information. The
      methods described here can be used to measure tissue volume, proliferation and
      cell size, to determine contribution and distribution of cell types in a tissue
      and to display this information in a quantitative 3D-reconstruction. Anat Rec,
      2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30289206
TI  - Corrigendum.

PMID- 30289207
TI  - Current status and future trends on automated multidimensional separation
      techniques employing sorbent-based extraction columns.
AB  - Determination of target analytes present in complex matrices requires a suitable
      sample preparation approach to efficiently remove the analytes of interest from a
      medium containing several interferers while at the same time preconcentrating
      them aiming to improve the output signal detection. Online multidimensional solid
      phase separation techniques have been widely used for the analysis of different
      contaminants in complex matrices such as food, environmental, and biological
      samples, among others. These online techniques usually consist of two steps
      performed in two different columns (extraction and analytical column), the first
      being employed to extract the analytes of interest from the original medium and
      the latter to separate them from the interferers. The extraction column in
      multidimensional techniques presents a relevant role since their variations as
      building material (usually a tube), sorbent material, modes of application, and
      so on can significantly influence the extraction success. The main features of
      such columns are subject of constant research aiming improvements directly
      related to the performance of the separation techniques that utilize
      multidimensional analysis. The present review highlights the main features of
      extraction columns online coupled to chromatographic techniques, inclusive for in
      tube solid-phase microextraction, online solid phase and turbulent flow, aiming
      the determination of analytes present at very low concentrations in complex
      matrices. It will critically describe and discuss some of the most common
      instrumental set up as well as comments on recent applications of these
      multidimensional techniques. Besides that, the authors have described some
      properties and enhancements of the extraction columns that are used as first
      dimension on these systems, such as type of column material (poly (ether ether
      ketone), fused silica, stainless steel, and other materials) and the way that the
      extractive phase is accommodated inside the tubing (filled and open tubular).
      Practical applications of this approach in fields such as environment, food, and
      bioanalysis are also presented and discussed.

PMID- 30289208
TI  - Neuropil Distribution in the Anterior Cingulate and Occipital Cortex of
      Artiodactyls.
AB  - Relatively little neuroscience research has been focused on artiodactyls. Recent
      observations of complex social interactions in domestic and wild species suggest
      that analyses of artiodactyl brain anatomy would be of comparative value. In this
      study, we examined how the distribution of cortical neuropil space (a proxy for
      connectivity) varies across representative members of this diverse clade. Using
      image analysis techniques, we quantified the neuropil space in the anterior
      cingulate cortex (ACC) and the occipital (putative primary visual) cortex (OC) of
      12 artiodactyl species from adult specimens. Additionally, we conducted a
      preliminary investigation of variation in ACC neuropil space in a developmental
      series of five white-tailed deer (Odocoileus virginianus). Results indicate a
      consistent pattern of greater neuropil space in the ACC in comparison to the OC
      among all species, and a gradual increase in ACC neuropil space toward maturity
      in the white-tailed deer. Given the taxa that have the greatest cortical neuropil
      space, we hypothesize that such enhanced connectivity might be needed to support
      behaviors such as group foraging and attentiveness to conspecifics. These results
      help advance a broader understanding of diversity in neural circuitry in
      artiodactyls and point to the need for more in-depth comparisons of cortical
      neuron morphology and organization in this relatively understudied taxonomic
      group. Anat Rec, 301:1871-1881, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30289209
TI  - Bromodomain Drug Discovery - the Past, the Present, and the Future.
AB  - With the bromodomain (BRD) inhibitor JQ1, a remarkable success story of BRD4 as a
      novel drug target has been set off that yielded many anti-cancer drugs that are
      now in clinical trials. But not all of the great prospects of BRDs as drug
      targets may become true. First evaluations of ongoing clinical trials revealed
      that treatment with BET-inhibitors can be accompanied with significant toxic side
      effects and the validation of the therapeutic benefit of BET-inhibitors compared
      to existing therapies is still pending. New strategies that may overcome possible
      obstacles in BRD drug discovery include combination therapies with other agents,
      dual target inhibitors, and proteolysis targeting chimeras (PROTACs).
      Furthermore, non-BET proteins seem promising drug targets as well. Most recently,
      BRDs have been identified as putative targets to treat parasitic diseases such as
      malaria. Milestones in BRD drug discovery are reviewed and promising new
      developments are evaluated.

PMID- 30289210
TI  - Immunopathogenesis of ophthalmological paraneoplastic syndromes: Recent findings.
AB  - The aim of this study was to summarize the current knowledge of paraneoplastic
      syndromes involving eyes. The main interest was the immunopathogenesis of the
      abovementioned entities. A web search was conducted using Medline, Web of Science
      and Scopus engines. Key words concerning ocular paraneoplastic syndromes (OPS)
      such as: "ocular paraneoplastic syndrome", "cancer-associated retinopathy",
      "cancer-associated cone dysfunction", "melanoma-associated retinopathy",
      "bilateral diffuse uveal melanocytic proliferation", and "paraneoplastic optic
      neuritis" were combined with "immunology", "immune response", "antibodies", or
      "autoantibodies". Numerous papers were found as a result of "ocular
      paraneoplastic syndrome" search and many of them matched the chosen criteria. We
      focused on the most recent papers - published in the last 5 years - and
      eventually, 92 items were found. Only several papers from each detailed category
      fulfilled both OPS and immunologic criteria. Site-specific paraneoplastic
      syndromes still remain a difficult clinical challenge. The immunopathogenesis of
      some of them seems to be more complex than previously thought.

PMID- 30289211
TI  - An evaluation of the effect on lower extremity fracture healing of collagen-based
      fusion material containing 2 different calcium phosphate salts: An experimental
      rat model.
AB  - BACKGROUND: Collagen-based synthetic bone grafts which contain tricalcium
      phosphate (TCP) and hydroxyapatite (HA), and collagen-based synthetic bone grafts
      containing only TCP have some advantages compared to autografts. Therefore, these
      grafts are frequently used to fill bone defects and pseudoarthrosis. OBJECTIVES:
      The aim of this study was to evaluate and compare the clinical, radiological and
      histopathological effects of TCP-HA and TCP alone + Type-1 collagen in healing
      lower extremity fractures in a pseudoarthrosis model in rat femurs. MATERIAL AND
      METHODS: A total of 36 female Wistar rats were randomly separated into 4 groups.
      Group 1 (n = 10) was the control group. A femur pseudoarthrosis model was created
      in Groups 2, 3 and 4. On the 90th day after the 1st surgery in Group 2 (n = 10),
      TCP-HA + Type-1 collagen was applied, in Group 3 (n = 10), TCP alone + type-1
      collagen was applied, and in Group 4 (n = 6, the placebo group), saline solution
      was applied. Fixation was performed with an intramedullar pin. After 60 days and
      clinical and radiological scoring, all animals were sacrificed and a
      histopathological evaluation of the pseudoarthrosis areas was conducted. RESULTS:
      In all the clinical, radiological and histopathological measurements used in the
      evaluations of the differences between the groups, a higher rate of union was
      determined in Group 2 (TCP-HA). No significant difference was determined between
      Group 3 and Group 4 in terms of union rates. CONCLUSIONS: The clinical,
      radiological and histopathological results of this study showed that TCP alone
      was less effective than TCP-HA in the union of a femur pseudoarthrosis model in
      rats. The reason for this difference was considered to be hydroxyapatite (HA).

PMID- 30289212
TI  - Gastroesophageal reflux disease: current views and prospects.
AB  - This review presents a detailed definition of gastroesophageal reflux disease
      (GERD) and data on its prevalence, etiological and pathogenetic factors. The
      clinical picture of the disease, its clinical "masks" and complications including
      Barrett's oesophagus and oesophageal carcinoma are discussed. Various diagnostic
      methods, such as oesophagofibroscopy, targeted biopsy, morphological studies,
      multichannel 24 hr pH-metry, etc. are considered. Classifications of GERD is
      presented with special reference to the original clinico-pathogenetic
      classification developed by one of the authors. The effectiveness of modern
      methods of GERD pharmacotherapy and surgical treatment is discussed.

PMID- 30289213
TI  - Hypothyroidism and cardiovascular system.
AB  - The article presents data on the relationship between thyroid dysfunction and
      cardiovascular diseases. The role of dyslipidemia, adipokines (adiponectin,
      leptin, resistin), C-reactive protein, deficiency of vitamin D3 in the
      development of cardiovascular disease in hypothyroidism is discussed. The article
      describes characteristics of myocardial remodeling, its dysfunction and their
      correlation with risk factors of cardiovascular diseases in patients with
      hypothyroidism.

PMID- 30289215
TI  - Pathogenetically targeted method for conservative treatment of obesity and
      overweight correction.
AB  - This review of literature presents modern pathogenetic treatment options for
      obesity and overweight correction including the optimization of the motor
      function, nutrition education, drug therapy, surgical techniques and
      psychotherapy. The need for a multidisciplinary approach to the development of
      combined treatment programs is underlined taking into account the multifactorial
      pathogenesis of obesity. A combination of optimal physical activity and diet
      therapy with active personal involvement in the process of recovery is
      accentuated among the priority areas of excess body weight correction, as well as
      the treatment and prevention of obesity. It is shown that the physical
      rehabilitation should focus on the individualization of the physical exertion,
      its adequate dosing and intensity control using heart rate monitors to ensure the
      safety and effectiveness of the training sessions. The article also presents data
      on the effectiveness of rational medical and other types of treatment of obesity
      when the adjustment of physical activities and nutrition is insufficient. In
      particular, the results of the world's largest observation program of safe weight
      loss for the treatment of patients with alimentary obesity held in Russia from
      2012 to 2015 are described.

PMID- 30289214
TI  - The Principles of primary prophylaxis of bleeding from oesophagealvaricies in
      patients with liver cirrhosis.
AB  - The principles of primary prevention of bleeding from esophageal varices in
      patients with liver cirrhosis are discussed with reference to the stage ofportal
      hypertension. The information was collectedfrom the PubMed database, Google
      Scholar retrieval system, Cochrane reviews, and lists of references from relevant
      publications for 1980-2015 using the key words "bleeding from esophageal
      varices", "prophylaxis", "portal hypertension". Inclusion criteria were confined
      to primary prophylaxis of bleeding from esophageal varices in patients with liver
      cirrhosis. The analysis showed that the drugs of choice for primary prophylaxis
      of bleeding from esophageal varices in patients with liver cirrhosis are non
      selective beta-adrenoblockers, but their application is indicated only in case of
      clinicallyl significant portal hypertension in patients with large and mediumsize
      esophageal varices. When the use of these drugs is contraindicated, endoscopic
      ligation of esophageal varices can be recommended.

PMID- 30289216
TI  - Personified strategy for the correction of cardiometabolic risk factors in the
      alien population of the Arctic.
AB  - Aim. To estimate the efficacy and prognostic value of individual consulting in
      Far North inhabitants during a 5 year survey. Materials and methods. 125 patients
      with metabolic syndrome were included in the study (24.8% women, 24.8% men, age
      median 45 years (39-48); p > 0.05). All the participants were divided into 2
      groups dependence on the consulting frequency in the framework of the non
      surgical body mass reduction programs (group 1 - single consulting, group 2 -
      repeated consultings in 12 months). Results. Individual consulting of patients
      with MS within 3 months after the onset of the study allowed the target body mass
      to be achieved in 50% of the patients in association with the reduction of
      atherogenic lipid fractions (p < 0,05), insulin resistance (p < 0,05),
      inflammation markers, hemostasis disorders markers (p < 0,05) and decrease in the
      number of patients with behavioral risk factors. Repeated educational module
      increased the relative probability 1,9 (95% CI 1,03-3,6) and odds ratio - 2.4
      (95% CI 1,01-5,4) of body mass maintenance within 24 months and also reduced the
      risk of type 2 DM development (Cox's F-Test: F = 2,7; p = 0,041) and
      atherogenicity of lipid profile after 5 year observations. Conclusion. Our
      results proves the necessity of active utilization of educational modules at
      least as often as once a year. For the successful use of these modules based at
      outpatient facilities of the Far North it is necessary to include a dietologist
      in the staff of prophylactic departments which encounters difficulty under the
      modern funding mode.

PMID- 30289218
TI  - The role of cytokine gene polymorphism in the formation of arterial hypertension
      associated with metabolic syndrome.
AB  - We investigated the association of polymorphisms of genes tumor necrosis factors
      and their receptors (-308G/A TNFa, +250A/G Lta, +36 A/G TNFR1, +1663 A/G TNFR2)
      with the predisposition to the development of essential hypertension (EH) and the
      features of its clinical course in patients with metabolic syndrome. It has been
      demonstrated that the molecular genetic marker +36G TNFR1 (OR=1,25) is involved
      in the formation EH in individuals with metabolic syndrome. The risk of stage III
      EH in patients with metabolic syndrome is enhanced by genetic variants -308GA
      TNFa (OR=2,72), -308A TNFa (OR=2,72), +250G Lta (OR=1,80), and combinations
      thereof -308A TNFa with +1663G TNFR2 (OR=3,85), +250G Lta with +36G TNFR1
      (OR=3,85), +250G Lta with +1663G TNFR2 (OR=3,85) while protective properties are
      inherent in -308GG TNFa (OR=0,32), +250AA Lta (OR=0,45), -308G TNFa (OR=0,37),
      +250A Lta (OR=0,56) and a combination of genetic markers -308GG TNFa with +250A
      Lta (OR=0,31), -308G TNFa with +250AA Lta (OR=0,39), -308G TNFa with +250A Lta
      (OR=0,31).

PMID- 30289219
TI  - Dynamics of cognitive disorders in patients with type 2 diabetes mellitus under
      effect of metabolic therapy.
AB  - The aim of this study was to investigate the efficiency of metabolic therapy in
      correction of cognitive impairment in patients with type 2 diabetes. We undertook
      the analysis of results of the treatment of cognitive dysfunction in 80 patients
      with a diagnosis of type 2 diabetes. All patients received basic hypoglycemic
      therapy. 32 patients (study group) received in addition to the basal glucose
      lowering therapy daily intravenous infusion of 10 mlcytoflavindiluted in 200 ml
      of a 0.9% sodium chloride solution for 10 days, followed by 2 tablets b.i.d. for
      25 days.The group of comparison consisted of 29 patients given in addition to the
      basal glucose-lowering therapy daily intravenous infusion of 24 ml (600 mg)
      thioctacid diluted in 200 mL of a 0.9% sodium chloride solution for 10 days.
      Thereafter, they received 1 tablet of thioctacid BV once daily for 30 days. The
      control group consisted of 19 patients who received basic hypoglycemic therapy
      without additional metabolic therapy.Inclusion of cytoflavin in the combined
      treatment of patients with type 2 diabetes ensured a more effective correction of
      cognitive impairment. There was a statistically significant improvement in
      optical-spatial activities (p = 0.001), attention (p = 0.001), abstract thinking
      (p = 0.046), and memory (p<0.001) compared to those in other groups, according to
      the MOS test. Positive dynamics was expressed as the improvement of the optical
      spatial activities by 9,8 +/- 10,3%, attention by 13,5 +/- 11,8%, abstract
      thinking by 7,0 +/- 8,9%, and memory by 23.0 +/- 14 6%. The study of variations
      of the serum level of brain neurotrophic factor (BDNF) over time during the
      treatment with metabolic preparations reveal edits statistically significant
      increase (p = 0.002) in the patients treated with cytoflavin compared with
      comparison (p = 0.139) and control (p = 0.078) groups. These results suggest the
      influence of cytoflavin on the processes of neuroplasticity under conditions of
      hyperglycemia, improvement of cerebral microcirculation and cerebroprotective
      action of this medication.

PMID- 30289220
TI  - The significance of calprotectin for the evaluation of activity of inflammation
      in ulcerative colitis.
AB  - The combination of clinical and instrumental methods with non-invasive markers of
      ulcerative colitis allows to predict the incidence of this disease and optimize
      conditions and quality of medical care. To-day, the use of non-invasive markers
      is a topical issuesince itprovidesa most informative screening test for the high
      accuracydetermination ofresidual faecal calprotectin.

PMID- 30289221
TI  - Comparative assessment of the effectiveness of treatment of pulmonary
      thromboembolism in elderly patients.
AB  - We compared the efficiency of treatment of 99 patientswith pulmonary
      thromboembolism using thrombolytic agents, surgical intervention, and
      anticoagulation therapy with heparin and vitamins K. The surgical treatment
      proved more efficient than the two other options.

PMID- 30289222
TI  - Correction of oxidative stress in patients with chronic cerebral ischemia.
AB  - A pilot study of the effect of the antioxidant drug ethylmethylhydroxypyridine
      malate on indicators of oxidative stress in patients with chronic cerebral
      ischemia. At 6 day course administration investigated the antioxidant in these
      patients significantly accelerates the process of generation of superoxide anion
      radical, established by lucigenin-depended chemiluminescence that probably
      regulate a feedback mechanism oxidase systems. This increases the activity of
      superoxide dismutase, and reduced the concentration of secondary peroxidation
      product - malondialdehyde, making reasonable use of antioxidants in the treatment
      of this pathology.

PMID- 30289223
TI  - Cooperation with patients - guarantee of successful treatment.
AB  - The aim of the study was to substantiate the necessity of efficient therapeutic
      cooperation between the doctor and the patient. The main factors determining such
      cooperation are considered including odontological behaviour of the physician,
      the choice of the adequate treatment model, compliance with the principles and
      rules of medical ethics, deontological requirements regulating the
      patient/physician relationship. Special attention is given to such issues as the
      doctor's authority, patient's confidence, and professional preparation of the
      first patient's visit. The authority of the physician depends on his professional
      skills and moral qualities, such as sense of duty, humanism, and love for his
      occupation. The causes behind failed relationships between the doctor and the
      patient are considered with special reference to deontological flaws on the part
      of the physician.

PMID- 30289224
TI  - Warding Off Cyber Threats to Health Care.
AB  - Security breaches and cyber attacks on the health care system are increasing, and
      such breaches now average $3.8 million in cost per attack, HHS reported.

PMID- 30289225
TI  - Avoid Toxic Gas Exposures.
AB  - Two 2016 OSHA enforcement cases are object lessons in the importance of using the
      latest gas monitoring technology to protect workers.

PMID- 30289226
TI  - Keep Hazmats in Their Containers.
AB  - Stocking spill response supplies such as squeegees, absorbents and wipes in areas
      where hazardous materials are used, handled, and stored allows employees to
      immediately respond to incidental spills.

PMID- 30289227
TI  - Five Important Features of PPE for Chemical and Biological Hazard Protection.
AB  - What challenges have you faced when selecting the best chemical protective
      clothing for your work environment?

PMID- 30289228
TI  - Not All Momentary Thermal Hazards Are Equal.
AB  - One of the biggest mistakes made in the workplace is in believing that, because a
      garment is flame resistant, it must be safe for all hazards. This simply is not
      the case.

PMID- 30289229
TI  - A Common-Sense Approach to Your Protection Eyewear Selection.
AB  - Doing your homework on the manufacturer you choose is of paramount importance.

PMID- 30289230
TI  - Look Beyond Basic Protection: Vital Considerations in Safety Eyewear.
AB  - By offering eyewear that is best suited to workers' safety needs first, followed
      closely by style, employers support a stronger culture of acceptance and
      compliance.

PMID- 30289231
TI  - Protecting Workers from Automated Machine Operations.
AB  - Plan ahead by providing proper machine guarding equipment sooner rather than
      later; if not to prepare for future regulations, do it to keep employees safe.

PMID- 30289232
TI  - Combining Safety Job Hazard Analysis & Lean Six Sigma to Improve Machine
      Guarding.
AB  - Similar to the Toyota Production System, we must all strive to eliminate waste
      (in our case, lost productivity from job hazard injuries) from our organizations.

PMID- 30289233
TI  - Managing Risk in Construction.
AB  - A safety professional must consider the levels of understanding to risk when
      working with sites or individuals. We are walking lessons learned, and that is
      our advantage.

PMID- 30289234
TI  - Early Vision Leadership.
AB  - Focus on earliest indicators of momentum. Actions taken usually don't blossom
      into statistical changes for a period of time.

PMID- 30289235
TI  - Three-Dimensional Nanostructured Palladium with Single Diamond Architecture for
      Enhanced Catalytic Activity.
AB  - Fuel cells are a key new green technology that have applications in both
      transport and portable power generation. Carbon-supported platinum (Pt) is used
      as an anode and cathode electrocatalyst in low-temperature fuel cells fueled with
      hydrogen or low-molecular-weight alcohols. The cost of Pt and the limited world
      supply are significant barriers to the widespread use of these types of fuel
      cells. Comparatively, palladium has a 3 times higher abundance in the Earth's
      crust. Here, a facile, low-temperature, and scalable synthetic route toward three
      dimensional nanostructured palladium (Pd) employing electrochemical templating
      from inverse lyotropic lipid phases is presented. The obtained single diamond
      morphology Pd nanostructures exhibited excellent catalytic activity and stability
      toward methanol, ethanol, and glycerol oxidation compared to commercial Pd black,
      and the nanostructure was verified by small-angle X-ray scattering, scanning
      tunneling electron microscopy, and cyclic voltammetry.

PMID- 30289236
TI  - Gene Dysfunction Mediates Immune Response to Dopaminergic Degeneration in
      Parkinson's Disease.
AB  - Many publications reported that genetic dysfunction mediates abnormal immune
      responses in the brain, which is important for the development of
      neurodegenerative diseases, especially for Parkinson's disease (PD). This immune
      disorder results in subsequent inflammatory reaction, which stimulates microglia
      or other immune cells to secrete cytokines and chemokines and disturbs the
      proportion of peripheral blood lymphocyte subsets contributing to dopaminergic
      (DA) neuron apoptosis. Furthermore, the abnormal immune related signal pathways
      caused by genetic variants promote chronic inflammation destroying the blood
      brain barrier, which allows infiltration of different molecules and blood cells
      into the central nervous system (CNS) exerting toxicity on DA neurons. As a
      result, the inflammatory reaction in the CNS accelerates the progression of
      Parkinson's disease and promotes alpha-synuclein aggregation and diffusion among
      DA neurons in the procession of Parkinson's disease. Thus, for disease
      evaluation, the genetic mediated abnormal immune response in PD may be assessed
      based on the multiple immune molecules and inflammatory factors, as well as the
      ratio of lymphocyte subsets from PD patient's peripheral blood as potential
      biomarkers.

PMID- 30289237
TI  - Tuning Microstructures of Graphene to Improve Power Capability of Rechargeable
      Hybrid Aqueous Batteries.
AB  - Low conductivity and structural degradation of LiMn2O4 lead to poor power
      capability and severe capacity fading of hybrid aqueous Zn/LiMn2O4 battery. Here,
      we propose an effective strategy by tuning the microstructures of graphene to
      optimize its electrical and interfacial properties and electrode dynamics of
      LiMn2O4/graphene cathodes, which successfully prompt significant improvements in
      electrical conductivity and structural stability, thus essentially leading to a
      promising electrochemical performance. More importantly, it reveals different
      electrochemical properties prompted by different conductivity, which mainly
      depends on the microstructures of graphene. This dependence is due to the
      influence of electronic channels and conductive paths on the conductivity of
      LiMn2O4/graphene electrodes. A well-designed mesoporous graphene composed of
      about two graphene-layers exhibits an excellent high-rate performance; even after
      300 cycles, a highly reversible capacity of 75 mAh g-1 is retained at 4C rate.
      The results of this study suggest that the structural tuning of electronic
      channels of graphene can be used as an effective means to improve the performance
      of LiMn2O4 cathodes in hybrid aqueous batteries.

PMID- 30289238
TI  - Ultraviolet Irradiation Treatment for Enhanced Sodium Storage Performance Based
      on Wide-Interlayer-Spacing Hollow C@MoS2@CN Nanospheres.
AB  - The photochemistry and sodium storage process have been generally considered as
      two separated approaches without strong connection. Here, ultraviolet (UV)
      irradiation was applied to sodium-ion batteries to improve the electrochemical
      performance of MoS2-based composites. C@MoS2@CN nanospheres consist of double
      protective structures, including inner hollow carbon spheres with a thin wall (C)
      and outer N-doping carbon nanosheets (CNs) derived from polydopamine. The special
      nanostructure possesses the virtues such as wide-interlayer spacing, flexible
      feature with great structure integrity, and rich active sites, which endow the
      fast electron transfer and shorten the ion diffusion pathways. Under the
      excitation of UV-light, intense electrons and holes are accumulated within MoS2
      based composites. The excited electrons can promote the preinsertion of Na+. More
      importantly, dense electrons promote the electrolyte to decompose and hence form
      a stable solid electrolyte interphase in advance. After UV-light irradiation
      treatment in the electrolyte, the initial Coulombic efficiency of C@MoS2@CN
      electrodes increased from 48.2 to 79.6%, and benefiting from the fine
      nanostructure, the C@MoS2@CN electrode with UV irradiation treatment delivered a
      great rate performance 116  mAh g-1 in 20 s and  super cycling stability that
      87.6% capacity was retained after 500 cycles at 500 mA g-1. When employed as
      anode for sodium-ion hybrid capacitors, it delivered a maximum power density of
      6.84 kW kg-1 (with 114.07  Wh kg-1 energy density) and a maximum energy density
      of 244.15 Wh g-1 (with 152.59 W kg-1 power density). This work sheds new
      viewpoints into the applications of photochemistry in the development of energy
      storage devices.

PMID- 30289239
TI  - Application of Electronic Counting Rules for Ligand-Protected Gold Nanoclusters.
AB  - Understanding special stability of numerous ligand-protected gold nanoclusters
      has always been an active area of research. In the past few decades, several
      theoretical models, including the polyhedral skeletal electron pair theory
      (PSEPT), superatom complex (SAC), and superatom network (SAN), among others, have
      been developed for better understanding the stabilities and structures of
      selected ligand-protected gold nanoclusters. This Account overviews the recently
      proposed grand unified model (GUM) to offer some new insights into the structures
      and growth mechanism of nearly all crystallized and predicted ligand-protected
      gold nanoclusters. The main conceptual advancement of the GUM is identification
      of the duet and octet rules on the basis of the "big data" of 70+ reported ligand
      protected gold nanoclusters. According to the two empirical rules, the cores of
      the gold nanoclusters can be regarded as being composed of two kinds of
      elementary blocks (namely, triangle Au3 and tetrahedron Au4), each having 2 e
      closed-shell valence electrons (referred as Au3(2 e) and Au4(2 e)), as well as
      the secondary block (icosahedron Au13) with 8 e closed-shell valence electrons
      (referred as Au13(8 e)). The two elementary blocks (Au3(2 e) and Au4(2 e)) and
      the secondary block (Au13(8 e)), from electron counting point of view, can be
      regarded as an analogy of the highly stable noble-gas atoms of He and Ne,
      respectively. In each elementary block, the Au atoms exhibit three different
      valence-electron states (i.e., 1 e, 0.5 e, and 0 e), depending on the type of
      ligands bonded with these Au atoms. Such three valence-electron states are coined
      as three "flavors" of gold (namely, bottom, middle, and top "flavor"), a term
      borrowed from the quark model in the particle physics. Upon application of the
      duet and octet rules with accounting the three valence states of gold atoms, the
      Au3(2 e), Au4(2 e), and Au13(8 e) blocks can exhibit 10 (denoted as Delta1
      Delta10), 15 (denoted as T1-T15), and 91 (denoted as I1-I91) variants of valence
      states, respectively. When packing these blocks (with distinct electronic states)
      together, it forms the gold core of ligand-protected gold nanocluster. As such,
      the special stabilities of the ligand-protected gold nanoclusters are explained
      based on the local stability of each block. With GUM, rich and complex structures
      of ligand-protected gold nanoclusters have been analyzed through structure
      anatomy. Moreover, the growth of these clusters can be simply viewed as
      sequential addition of the blocks, rather than as addition of the gold atoms.
      Another useful application of the GUM is to analyze the structural isomerism. The
      three types of isomerism for the gold nanoclusters, i.e., core, staple, and
      complex isomerism, can be considered as an analogy of chain, point, and
      functional isomerism (known in organic chemistry), respectively. GUM can be
      applied to predict new clusters, thereby guiding experimental synthesis. Indeed,
      a number of ligand-protected gold nanoclusters with high stabilities were
      rationally designed based on the GUM.

PMID- 30289240
TI  - Hierarchical Nanosheet-Based MS2 (M = Re, Mo, W) Nanotubes Prepared by Templating
      Sacrificial Te Nanowires with Superior Lithium and Sodium Storage Capacity.
AB  - Hierarchical nanosheet-based nanotubes are very attractive because their unique
      structure endows them with large surface areas and exposes massive active sites
      for functional applications. We herein demonstrate a facile one-pot hydrothermal
      approach to fabricate the hierarchical nanosheet-based MS2 (M = Re, Mo, W)
      nanotubes by using Te nanowires as sacrificial templates. The hierarchical
      nanotubes show tube channels of ~30 nm and hierarchical channel walls with a
      tunable thickness of up to ~50 nm. As exemplified for application in Li-ion and
      Na-ion batteries, the ReS2 hierarchical nanotubes exhibit excellent specific
      capacities (1137 mA h g-1 for Li-ion batteries and 375 mA h g-1 for Na-ion
      batteries at 0.1 A g-1 after 100 cycles), good cycling stabilities, and high rate
      capabilities, demonstrating their promising applicability in rechargeable
      batteries. This work may open up new opportunities for further exploration of new
      types of hierarchical nanostructures for applications, e.g., in catalysis, energy
      chemistry, and gas adsorption and separation.

PMID- 30289241
TI  - Directing Charge Transfer in Quantum Dot Assemblies.
AB  - The optical and electronic properties of semiconductor quantum dots (QDs) make
      them attractive candidates for applications in photovoltaics, spintronics,
      photocatalysis, and optoelectronics. Understanding how to control the flow of
      charge in QD assemblies is essential for realizing novel applications. This
      Account explores some unique characteristics of charge transport in QD dyads,
      triads, and their assemblies. The emerging features of these assemblies that
      provide new opportunities to manipulate charge flow at the nanoscale are (1)
      cascading energy landscapes and band offsets to inhibit charge recombination, (2)
      electrostatic fields that direct charge flow through QD-QD and QD-conjugated
      polymer junctions, and (3) QD chirality and chiral imprinting that promotes
      vectorial electron and spin selective transport. Charge flow kinetics is
      determined by a combination of familiar electron transfer parameters (reaction
      free energy, reorganization energy, and electronic coupling), donor and acceptor
      electronic densities of states, and internal electric fields. Electron transfer
      and electronic structure theory, combined with kinetic modeling, place the
      measured kinetics of QD electron transfer donor-acceptor assemblies into a
      unified conceptual context. The experimental transfer rates measured in these
      systems depend upon structure and the internal electric fields that are present
      in the assemblies. A negatively charged donor and positively charged acceptor,
      for example, facilitates (inhibits) electron (hole) transfer, while an electric
      field of opposite orientation (reversal of charges) inhibits (promotes) electron
      (hole) transfer. These and other emerging rules that govern charge flow in NP
      assemblies provide a strategy to design the directionality and yield of
      interfacial charge transport. Chirality at the nanoscale can induce spin
      selective charge transport, providing new ways to direct charge (and spin) flow
      in QD assemblies. Magnetoresistance and magnetic conductive probe atomic force
      microscopy experiments show spin selective electron transport for chirally
      imprinted QD assemblies. Photoinduced electron transfer from achiral donor-QDs to
      chiral acceptor-QDs depends on the electron spin and chiroptical properties of
      the acceptor-QDs. These assemblies show transport characteristics that correlate
      with features of the QDs' circular dichroism spectra, presenting intriguing
      challenges to theory, and indicating that spectroscopic signatures may assist in
      the design and diagnosis of functional molecular assemblies. Theoretical and
      experimental studies of charge transport in well-defined QD assemblies are
      establishing design principles for vectorial charge transport and are also
      refining questions surrounding the mechanism and control of these processes.
      These intensified efforts are forging links between fundamental discoveries
      regarding mechanism and practical applications for these novel assembled
      nanostructures.

PMID- 30289242
TI  - Simultaneous and Independent Dual Site-Specific Self-Labeling of Recombinant
      Antibodies.
AB  - Antibody-based diagnostic and therapeutic reagents armed with effector molecules
      such as dyes and drugs offer hope in the battle against cancer. Several site
      specific conjugation methods have been developed to equip antibodies with such
      effector molecules, but they tend to be expensive and involve multiple reaction
      steps. The conjugation of two different effector molecules to a single antibody
      also remains a major challenge. Here we describe a simple, controlled, and robust
      method for the dual site-specific conjugation of an antibody with two effector
      molecules in a single-pot reaction using the self-labeling SNAP and CLIP protein
      tags. We verified the principle of the method by labeling an epidermal growth
      factor receptor (EGFR)-specific single-chain antibody fragment (scFv-425)
      simultaneously with IRDye700 and Alexa-Fluor647. This dual-labeled antibody bound
      to EGFR+ ovarian cancer cell lines and tissue samples with high specificity, and
      its phototherapeutic efficacy was confirmed by the selective killing of EGFR+
      cells in vitro.

PMID- 30289243
TI  - Metal Coordination Polymer Framework Governed by Heat of Hydration for
      Noninvasive Differentiation of Alkali Metal Series.
AB  - We illustrate that the extent of hydration and consequently the heat of hydration
      of alkali metal ions can be utilized to control their insertion/deinsertion
      chemistry in a redox active metal coordination polymer framework (CPF) electrode.
      The formal redox potential of CPF electrode for cation intercalation is inversely
      correlated to hydrated ionic radii, with clear distinction between the
      intercalation of ions across alkali metal series. This leads to noninvasive
      identification and differentiation of cations in the alkali metal series by
      utilizing a single sensing platform.

PMID- 30289244
TI  - Probing Electrocatalysis at Individual Au Nanorods via Correlated Optical and
      Electrochemical Measurements.
AB  - A novel analytical methodology based on correlated optical and electroanalytical
      measurements was developed to probe electrocatalytic reactions at individual
      nanoparticles (NPs) with well-defined geometries. The developed methodology,
      Optically Targeted ElectroChemical Cell Microscopy (OTECCM), relies on a
      combination of optical hyperspectral imaging, to locate individual NPs and
      provide structural information, and Scanning ElectroChemical Cell Microscopy
      (SECCM), to provide direct information on the electrochemical behavior of the
      same NPs. This complementary strategy allows for SECCM measurements to be carried
      out in a "targeted" fashion, offering significant throughput advantages over
      conventional, scanning-based approaches. The developed methodology was applied to
      study the electrocatalytic oxidation of hydrazine at individual Au nanorods
      (NRs). Correlated electron microscopy investigations were carried out to
      conclusively demonstrate the ability of the proposed methodology to probe
      electrochemical reactions at individual NRs. A wide variety in behavior of the
      individual NRs was observed, with surface reactions at Au playing a prominent
      role in the observed response. In situ spectroscopic investigations at individual
      NRs suggest surface restructuring and/or residual ligand desorption leads to
      significant changes in catalytic activity over time. Results from the correlated
      electron microscopy investigations as well as the statistical analyses of data
      obtained for hundreds of individual nanostructures suggest that the gross
      geometry of a NR is a poor predictor of its electrocatalytic performance.

PMID- 30289245
TI  - Label-Free, Single-Particle, Colorimetric Detection of Permanganate by GNPs@Ag
      Core-Shell Nanoparticles with Dark-Field Optical Microscopy.
AB  - Rapid quantification of permanganate (MnO4-) in aqueous solution with a
      convenient and sensitive single-particle-detection (SPD) method is demonstrated
      by dark-field optical microscopy. The design is based on the selective etching of
      the Ag shell of a glucose-protected GNPs@Ag nanoparticle by MnO4-. In the
      presence of MnO4-, a noticeable red-shift of localized surface-plasmon resonance
      (LSPR, from blue to green) together with a tremendous decrease in the extinction
      coefficient from individual GNPs@Ag nanoparticles is observed. MnO4- can then be
      quantified by calculating the ratio between the number of green and blue
      particles on the cover glass surface after the etching process. A linear dynamic
      range of 0-6 MUM and a limit of detection (LOD) as low as 46 nM were readily
      achieved, which are much lower than those of spectroscopic measurements in bulk
      solution. In tap water, a comparable LOD (50 nM) and satisfactory recovery
      efficiency are demonstrated. As a consequence of these merits, the method
      demonstrated herein will find promising applications for the ultrasensitive
      detection of MnO4- under complex milieu in the future.

PMID- 30289246
TI  - A Slick Solution to a Sticky Problem.

PMID- 30289247
TI  - Methane Activation by Gas Phase Atomic Clusters.
AB  - The increasing supply of natural gas has created a strong demand for developing
      efficient catalytic processes to upgrade methane, the most stable alkane
      molecule, into value-added chemicals. Currently, methane conversion in laboratory
      and industry is mostly performed under high-temperature conditions. A lot of
      effort has been devoted to exploring chemical entities that are able to activate
      the C-H bond of methane at lower temperatures, preferably room temperature. Gas
      phase atomic clusters with limited numbers of atoms are ideal models of active
      sites on heterogeneous catalysts. The cluster systems are being actively studied
      to activate methane under room-temperature conditions. State-of-the-art mass
      spectrometry, photoelectron imaging spectroscopy, and quantum chemistry
      calculations have been combined in our laboratory to reveal the molecular-level
      mechanisms of methane activation by atomic clusters. In this Account, we
      summarize our recent progress on thermal methane activation by metal oxide
      clusters doped with noble-metal atoms (Au, Pt, and Rh) as well as by oxygen-free
      species including carbides and borides of base metals (V, Ta, Mo, and Fe). In
      contrast to the generations of CH3* free radicals in many of the previously
      reported cluster reactions with methane, the generations of stable products such
      as formaldehyde, acetylene, and syngas as well as closed-shell species AuCH3 and
      B3CH3 have been identified for the cluster reaction systems herein. Besides the
      well recognized mechanisms of methane activation by the O-* radicals through
      hydrogen atom abstraction and by metal atoms through oxidative addition, the new
      mechanisms of synergistic methane activation by Lewis acid-base pairs (such as
      Audelta+-Odelta- and Bdelta+-Bdelta-) and by dinuclear metal centers (such as Ta
      Ta) have been recently revealed. In the reactions between methane and oxide
      clusters doped with noble-metal atoms, the oxide cluster "supports" can accept
      the H atoms and the CH x species delivered through the noble-metal atoms and then
      transform methane into stable oxygenated compounds. The product selectivity (such
      as formaldehyde versus syngas) can be controlled by different noble-metal atoms
      (such as Pt versus Rh). The electronic structures of base metal centers can be
      engineered through carburization so that the low-spin states can be accessible to
      reduce the C-H bond of methane. Such active base metal centers in low-spin states
      resemble related noble-metal atoms in methane activation. The boron clusters
      (such as B3 in VB3+) can be polarized by the metal cations to form the Lewis acid
      base pair Bdelta+-Bdelta- to cleave the C-H bond of methane very easily. These
      molecular-level mechanisms may well be operative in related heterogeneous
      catalysis and can be a fundamental basis to design efficient catalysts for
      activation and conversion of methane under mild conditions.

PMID- 30289248
TI  - Photoelectrochemical Approach to Apoptosis Evaluation via Multi-Functional
      Peptide- and Electrostatic Attraction-Guided Excitonic Response.
AB  - The excitonic response between nanomaterials is distance-dependent, and thus,
      interparticle distance is a key factor in fabricating diverse
      photoelectrochemical (PEC) systems. Current studies focus on DNA-mediated
      regulation of interparticle distance. However, limited by high demands of base
      pairing and flexibility of DNA, it is hard for DNA to achieve precise regulation,
      especially in a short distance. To pursue better PEC performances in bioanalyses,
      alternative biological materials should be explored to replace DNA as new
      "distance controllers". In this work, a peptide with three functional sequences
      is designed to control interparticle distance between positive-charged Au
      nanoparticles ((+) AuNPs) and negative-charged CdTe quantum dots ((-) CdTe QDs).
      Relying on the function of binding sequence, (+) AuNPs and (-) CdTe QDs may be
      separated to a certain distance by the multifunctional peptide. In this case, the
      excitonic response is relatively weak, and an evident PEC response can be
      observed. Because it contains the substrate sequence of caspase-3, the peptide is
      cleaved in the presence of caspase-3. As a result, without the support of intact
      peptide, electrostatic attraction plays a dominant role, leading to the
      aggregation of oppositely charged AuNPs and CdTe QDs, which strengthens the
      excitonic response and attenuates the PEC response. On the basis of these
      principles, a novel PEC approach was fabricated to sensitively quantify caspase
      3. Meanwhile, caspase-3 in staurosporine-treated A549 cells are also determined
      by the approach, and the obtained results agree well with the fluorescent
      intensity of confocal images, manifesting that the proposed PEC method can
      monitor apoptosis in a label-free strategy. Overall, the study reveals the
      capability of peptides in controlling interparticle distance of nanomaterials,
      which may accelerate the development of peptide-based PEC analytical methods.

PMID- 30289249
TI  - Machine Learning Algorithms for Liquid Crystal-Based Sensors.
AB  - We present a machine learning (ML) framework to optimize the specificity and
      speed of liquid crystal (LC)-based chemical sensors. Specifically, we demonstrate
      that ML techniques can uncover valuable feature information from surface-driven
      LC orientational transitions triggered by the presence of different gas-phase
      analytes (and the corresponding optical responses) and can exploit such feature
      information to train accurate and automatic classifiers. We demonstrate the
      utility of the framework by designing an experimental LC system that exhibits
      similar optical responses to a stream of nitrogen containing either 10 ppmv
      dimethyl-methylphosphonate (DMMP) or 30% relative humidity (RH). The ML framework
      is used to process and classify thousands of images (optical micrographs)
      collected during the LC responses and we show that classification (sensing)
      accuracies of over 99% can be achieved. For the same experimental system, we
      demonstrate that traditional feature information used in characterizing LC
      responses (such as average brightness) can only achieve sensing accuracies of
      60%. We also find that high accuracies can be achieved by using time snapshots
      collected early in the LC response, thus providing the ability to create fast
      sensors. We also show that the ML framework can be used to systematically analyze
      the quality of information embedded in LC responses and to filter out noise that
      arises from imperfect LC designs and from sample variations. We evaluate a range
      of classifiers and feature extraction methods and conclude that linear support
      vector machines are preferred and that high accuracies can only be achieved by
      simultaneously exploiting multiple sources of feature information.

PMID- 30289250
TI  - Cerium-Catalyzed Formal Cycloaddition of Cycloalkanols with Alkenes through Dual
      Photoexcitation.
AB  - We describe a synergistic utilization of cerium photocatalysis and photoinduced
      electron transfer catalysis that enables an atom- and step-economical ring
      expansion of readily available cycloalkanols. This operationally simple protocol
      provides rapid access to privileged and synthetically challenging bridged
      lactones. The mild catalytic manifold has been adapted to continuous flow for
      scale-up applications and employed for the concise synthesis of polycyclic core
      of nepalactones.

PMID- 30289252
TI  - Efficient and Accurate Hydration Site Profiling for Enclosed Binding Sites.
AB  - Molecular dynamics (MD) simulations allow for accurate prediction of the
      thermodynamic profile of binding-site water molecules critical for protein-ligand
      association. Whereas this hydration-site profiling converges rapidly for solvent
      exposed sites independent of the initial water placement, an accurate and
      reliable placement is required for water molecules in occluded binding sites.
      Here, we present an accurate and efficient hydration-site prediction method for
      occluded binding sites combining water placement based on 3D-RISM and MD
      simulations using WATsite.

PMID- 30289251
TI  - Half-Sandwich Iridium and Ruthenium Complexes: Effective Tracking in Cells and
      Anticancer Studies.
AB  - Half-sandwich metal-based anticancer complexes suffer from uncertain targets and
      mechanisms of action. Herein we report the observation of the images of half
      sandwich iridium and ruthenium complexes in cells detected by confocal
      microscopy. The confocal microscopy images showed that the cyclopentadienyl
      iridium complex 1 mainly accumulated in nuclei in A549 lung cancer cells, whereas
      the arene ruthenium complex 3 is located in mitochondria and lysosomes, mostly in
      mitochondria, although both complexes entered A549 cells mainly through energy
      dependent active transport. The nuclear morphological changes caused by Ir
      complex 1 were also detected by confocal microscopy. Ir complex 1 is more potent
      than cisplatin toward A549 and HeLa cells. DNA binding studies involved
      interaction with the nucleobases 9-ethylguanine, 9-methyladenine, ctDNA, and
      plasmid DNA. The determination of bovine serum albumin binding was also
      performed. Hydrolysis, stability, nucleobase binding, and catalytic NAD+/NADH
      hydride transfer tests for complexes 1 and 3 were also carried out. Both
      complexes activated depolarization of mitochondrial membrane potential and
      intracellular ROS overproduction and induced cell apoptosis. Complex 3 arrested
      the cell cycle at the G0/G1 phase by inactivation of CDK 4/cyclin D1. This work
      paves the way to track and monitor half-sandwich metal complexes in cells, shines
      a light on understanding their mechanism of action, and indicates their potential
      application as theranostic agents.

PMID- 30289254
TI  - Sensoproteomics: A New Approach for the Identification of Taste-Active Peptides
      in Fermented Foods.
AB  - Aiming at the identification of the key bitter peptides in fermented foods, a new
      approach, coined "sensoproteomics", was developed and applied to fresh cheese
      samples differing in bitter taste intensity. By means of MPLC fractionation of
      the water-soluble cheese extracts in combination with taste dilution analysis,
      complex fractions with intense bitter taste were located and then screened by
      UPLC-MS/MS for the entire repertoire of ~1600 candidate peptides, extracted from
      a literature meta-analysis on dairy products, by using a total of 120 selected
      reaction monitoring methods computed in silico. A total of 340 out of the 1600
      peptides were found in the cheese samples, among which 17 peptides were
      identified as candidate bitter peptides by considering only peptides that were
      located in the bitter-tasting MPLC fractions (signal-to-noise ratio: >=10) with a
      fold-change of >=3 when comparing the less bitter to the more bitter cheese
      sample and that were validated by comparison with the synthetic reference
      peptides. While EIVPNS[phos]VEQK (alphas1-CN70-78) and INTIASGEPT (kappa-CN122
      131) did not exhibit any bitter taste up to 2000 MUmol/L, 15 of the 17 target
      peptides showed bitter taste thresholds ranging from 30 (ARHPHPHLSFM, kappa-CN96
      106) to 690 MUmol/L (IQKEDVPS, alphas1-CN81-88). Finally, quantitative peptide
      analysis followed by calculation of dose-overthreshold factors revealed a primary
      contribution of MAPKHKEMPFPKYPVEPF (beta-CN102-119) and ARHPHPHLSFM (kappa-CN96
      106) to the perceived bitter taste of the fresh cheese samples. Finally, the
      evolution of the bitter peptides throughout two different fresh cheese
      manufacturing processes was quantitatively recorded.

PMID- 30289253
TI  - Unexplored Nucleotide Binding Modes for the ABC Exporter MsbA.
AB  - The ATP-binding cassette (ABC) transporter MsbA is an ATP-driven lipid-A
      flippase. It belongs to the ABC protein superfamily whose members are
      characterized by conserved motifs in their nucleotide binding domains (NBDs),
      which are responsible for ATP hydrolysis. Recently, it was found that MsbA could
      catalyze a reverse adenylate kinase (rAK)-like reaction in addition to ATP
      hydrolysis. Both reactions are connected and mediated by the same conserved NBD
      domains. Here, the structural foundations underlying the nucleotide binding to
      MsbA were therefore explored using a concerted approach based on conventional-
      and DNP-enhanced solid-state NMR, pulsed-EPR, and MD simulations. MsbA
      reconstituted into lipid bilayers was trapped in various catalytic states
      corresponding to intermediates of the coupled ATPase-rAK mechanism. The analysis
      of nucleotide-binding dependent chemical shift changes, and the detection of
      through-space contacts between bound nucleotides and MsbA within these states
      provides evidence for an additional nucleotide-binding site in close proximity to
      the Q-loop and the His-Switch. By replacing Mg2+ with Mn2+ and employing pulsed
      EPR spectroscopy, evidence is provided that this newly found nucleotide binding
      site does not interfere with the coordination of the required metal ion.
      Molecular dynamic (MD) simulations of nucleotide and metal binding required for
      the coupled ATPase-rAK mechanism have been used to corroborate these experimental
      findings and provide additional insight into nucleotide location, orientation,
      and possible binding modes.

PMID- 30289255
TI  - Interactions between the Molecular Components of the Cowpea Chlorotic Mottle
      Virus Investigated by Molecular Dynamics Simulations.
AB  - The formation of a viral particle generally involves hundreds of proteins, making
      the assembly process intricate. Despite its intrinsic complexity, the production
      of a viral particle begins through the interaction between the basic assembly
      components. For the cowpea chlorotic mottle virus (CCMV), the first steps of the
      assembly process involve dimers of the capsid protein. Here, we carried out
      atomistic molecular dynamics simulations to investigate the initial assembly
      process of CCMV to get insight into the interactions at the molecular level. We
      found that salinity not only affects the electrostatic interactions between
      dimers but also changes the conformation of the positively charged N-terminal
      tails and can cause a serious steric hindrance for other dimers binding to the
      hydrophobic domains. An RNA rod was used to mimic a long segment of a viral
      genome and to study its interaction with dimers. We observed that the dimer with
      tails prefers to bind on the RNA rod with its positively charged inner side. The
      dimer-RNA interaction was found to be as strong as the dimer-dimer interaction,
      whereas the association energies between a dimer and a pentamer or a hexamer of
      dimers were high but strongly depended on the presence of the tails. Upon
      heating, the capsid experienced a shrinkage accompanied by a loss of order in the
      icosahedral crystal structure.

PMID- 30289256
TI  - Quantitative Evaluation of Optical Free Carrier Generation in Semiconducting
      Single-Walled Carbon Nanotubes.
AB  - Gauging free carrier generation (FCG) in optically excited, charge-neutral single
      walled carbon nanotubes (SWNTs) has important implications for SWNT-based
      optoelectronics that rely upon conversion of photons to electrical current.
      Earlier investigations have largely provided only qualitative insights into
      optically triggered SWNT FCG, due to the heterogeneous nature of commonly
      interrogated SWNT samples and the lack of direct, unambiguous spectroscopic
      signatures that could be used to quantify charges. Here, employing ultrafast pump
      probe spectroscopy in conjunction with chirality-enriched, length-sorted, ionic
      polymer-wrapped SWNTs, we develop a straightforward approach for quantitatively
      evaluating the extent of optically driven FCG in SWNTs. Owing to the previously
      identified trion transient absorptive hallmark (Tr+11 -> Tr+nm) and the rapid
      nature of trion formation dynamics (<1 ps) relative to established free-carrier
      decay time scales (>ns), we correlate FCG with trion formation dynamics.
      Experimental determination of the trion absorptive cross section further enables
      evaluation of the quantum yields for optically driven FCG [Phi(E nn->h ++e -)] as
      a function of optical excitation energy and medium dielectric strength. We show
      that (i) E33 excitons give rise to dramatically enhanced Phi(E nn->h ++e -)
      relative to those derived from E22 and E11 excitons and (ii) Phi(E33->h ++e -)
      monotonically increases from ~5% to 18% as the solvent dielectric constant
      increases from ~32 to 80. This work highlights the extent to which the nature of
      the medium and excitation conditions control FCG quantum yields in SWNTs: such
      studies have the potential to provide new design insights for SWNT-based
      compositions for optoelectronic applications that include photodetectors and
      photovoltaics.

PMID- 30289257
TI  - GNE-371, a Potent and Selective Chemical Probe for the Second Bromodomains of
      Human Transcription-Initiation-Factor TFIID Subunit 1 and Transcription
      Initiation-Factor TFIID Subunit 1-like.
AB  - The biological functions of the dual bromodomains of human transcription
      initiation-factor TFIID subunit 1 (TAF1(1,2)) remain unknown, although TAF1 has
      been identified as a potential target for oncology research. Here, we describe
      the discovery of a potent and selective in vitro tool compound for TAF1(2),
      starting from a previously reported lead. A cocrystal structure of lead compound
      2 bound to TAF1(2) enabled structure-based design and structure-activity
      relationship studies that ultimately led to our in vitro tool compound, 27 (GNE
      371). Compound 27 binds TAF1(2) with an IC50 of 10 nM while maintaining excellent
      selectivity over other bromodomain-family members. Compound 27 is also active in
      a cellular-TAF1(2) target-engagement assay (IC50 = 38 nM) and exhibits
      antiproliferative synergy with the BET inhibitor JQ1, suggesting engagement of
      endogenous TAF1 by 27 and further supporting the use of 27 in mechanistic and
      target-validation studies.

PMID- 30289258
TI  - Formation of Enormously Strongly Bound Anionic Clusters Predicted in Binary
      Superacids.
AB  - The possible formation of the (AlF4(HF) n)- ( n = 1-8 and 12), (AsF6(HF) n)-, and
      (SbF6(HF) n)- ( n = 1-6 and 12) anionic clusters of a superhalogen nature is
      predicted in the solutions of binary HF/AlF3, HF/AsF5, and HF/SbF5 Lewis-Bronsted
      superacids on the basis of ab initio calculations. Our results show that all
      systems investigated represent extremely strongly bound anions characterized by
      vertical electron detachment energies (VDEs) that significantly exceed 10 eV. The
      VDE values estimated for the (AlF4(HF)12)-, (AsF6(HF)12)-, and (SbF6(HF)12)-
      systems are predicted to be 13.96, 14.03, and 14.03 eV, respectively, and are the
      largest vertical electron detachment energies reported in the literature thus
      far.

PMID- 30289259
TI  - Asymmetric Boron-Cored Aggregation-Induced Emission Luminogen with Multiple
      Functions Synthesized through Stepwise Conversion from a Symmetric Ligand.
AB  - Multifunction luminogens have emerged as promising candidates in high-performance
      sensor and imaging systems. Concise approaches to the synthesis of such molecules
      are urgently required both for fundamental research and technological
      applications. In this study, a new symmetric ligand of di(2
      hydroxyphenyl)phthalazine with multiple binding sites around a phthalazine unit
      was readily synthesized, which could be converted efficiently into an asymmetric
      luminogen (OBN-DHPP) through the formation of oxygen-boron-nitrogen bonding. This
      molecule has a twistable pi-extended backbone with a tetracoordinated boron core
      bearing two bulky phenyl groups, giving it abundant optical properties including
      a large Stokes shift piezochromism and aggregation-induced emission enhancement.
      Importantly, the presence of a free phenolic hydroxyl group in the backbone of
      OBN-DHPP enables the incorporation of various functional moieties into the
      asymmetric luminogen. As an example, polyethylene glycol (PEG)-modified luminogen
      (OBN-DHPP-PEG45) was synthesized. In the aqueous medium, OBN-DHPP-PEG45 could
      self-assemble into spherical nanoparticles with low cytotoxicity and excellent
      emission performance as well as high solubility. The results of flow cytometry
      and fluorescence microscopy reveal that these nanoparticles could be internalized
      successfully by HeLa cells, demonstrating their potential application in
      bioimaging.

PMID- 30289260
TI  - Dihydroxyacetone Production in the Nectar of Australian Leptospermum Is Species
      Dependent.
AB  - This study is the first large-scale survey of the presence of dihydroxyacetone
      (DHA) in the nectar of the Australian Leptospermum tree species. The work
      undertaken supports the growing global demand for bioactive Leptospermum honey.
      Leptospermum honey derived from L. scoparium in New Zealand, also referred to as
      Manuka honey, has a reputation for wound-healing and antimicrobial properties,
      which is based on its methylglyoxal (MGO) content. High-DHA nectar correlates to
      high-MGO honey, but not all Leptospermum species produce DHA in their nectar.
      This study investigates 55 of the 84 Leptospermum species native to Australia for
      their DHA-producing capability, with the DHA to total sugar (DHA:Tsugar) ratio of
      nectar samples determined by HPLC-PDA. DHA:Tsugar ranged from nondetectable in L.
      laevigatum, L. coriaceum, and L. trinervium to >16 000 mg/kg in L. speciosum and
      L. whitei. High-DHA Leptospermum species were identified for beekeepers to target
      for honey production and plantation development.

PMID- 30289261
TI  - Cell Volume Controls Protein Stability and Compactness of the Unfolded State.
AB  - Macromolecular crowding is widely accepted as one of the factors that can alter
      protein stability, structure, and function inside cells. Less often considered is
      that crowding can be dynamic: as cell volume changes, either as a result of
      external duress or in the course of the cell cycle, water moves in or out through
      membrane channels, and crowding changes in tune. Both theory and in vitro
      experiments predict that protein stability will be altered as a result of
      crowding changes. However, it is unclear how much the structural ensemble is
      altered as crowding changes in the cell. To test this, we look at the response of
      a FRET-labeled kinase to osmotically induced volume changes in live cells. We
      examine both the folded and unfolded states of the kinase by changing the
      temperature of the media surrounding the cell. Our data reveals that crowding
      compacts the structure of its unfolded ensemble but stabilizes the folded
      protein. We propose that the structure of proteins lacking a rigid, well-defined
      tertiary structure could be highly sensitive to both increases and decreases in
      cell volume. Our findings present a possible mechanism for disordered proteins to
      act as sensors and actuators of cell cycle or external stress events that
      coincide with a change in macromolecular crowding.

PMID- 30289263
TI  - K2S2O8-Mediated Selective Trifluoromethylacylation and Trifluoromethylarylation
      of Alkenes under Transition-Metal-Free Conditions: Synthetic Scope and
      Mechanistic Studies.
AB  - A practical and efficient method for selective intramolecular radical
      trifluoromethylacylation and -arylation of alkenes with inexpensive CF3SO2Na and
      K2S2O8 in aqueous media has been developed, respectively, affording the highly
      chemoselective synthesis of CF3-functionalized chroman-4-ones and chromanes in
      satisfactory yields. Control experiments and DFT calculations indicate that the
      CF3SO2Na/K2S2O8 system is capable of trifluoromethylating the substrate of
      alkenes without a transition metal catalyst and the oxidation of CF3SO2Na to .CF3
      by K2S2O8 is involved in the rate-determining step.

PMID- 30289262
TI  - Amino Acid Stabilization of Nucleic Acid Secondary Structure: Kinetic Insights
      from Single-Molecule Studies.
AB  - Amino acid and nucleic acid interactions are central in biology and may have
      played a role in the evolutionary development of protein-based life from an early
      "RNA Universe." To explore the possible role of single amino acids in promoting
      nucleic acid folding, single-molecule Forster resonance energy transfer
      experiments have been implemented with a DNA hairpin construct (7 nucleotide
      double strand with a 40A loop) as a simple model for secondary structure
      formation. Exposure to positively charged amino acids (arginine and lysine) is
      found to clearly stabilize the secondary structure. Kinetically, each amino acid
      promotes folding by generating a large increase in the folding rate with little
      change in the unfolding rate. From analysis as a function of temperature,
      arginine and lysine are found to significantly increase the overall exothermicity
      of folding while imposing only a small entropic penalty on the folding process.
      Detailed investigations into the kinetics and thermodynamics of this amino acid
      induced folding stability reveal arginine and lysine to interact with nucleic
      acids in a manner reminiscent of monovalent cations. Specifically, these
      observations are interpreted in the context of an ion atmosphere surrounding the
      nucleic acid, in which amino acid salts stabilize folding qualitatively like
      small monovalent cations but also exhibit differences because of the composition
      of their side chains.

PMID- 30289264
TI  - Energy-Resolved Photoconductivity Mapping in a Monolayer-Bilayer WSe2 Lateral
      Heterostructure.
AB  - Vertical and lateral heterostructures of van der Waals materials provide
      tremendous flexibility for band-structure engineering. Because electronic bands
      are sensitively affected by defects, strain, and interlayer coupling, the edge
      and heterojunction of these two-dimensional (2D) systems may exhibit novel
      physical properties, which can be fully revealed only by spatially resolved
      probes. Here, we report the spatial mapping of photoconductivity in a monolayer
      bilayer WSe2 lateral heterostructure under multiple excitation lasers. As the
      photon energy increases, the light-induced conductivity detected by microwave
      impedance microscopy first appears along the heterointerface and bilayer edge,
      then along the monolayer edge, inside the bilayer area, and finally in the
      interior of the monolayer region. The sequential emergence of mobile carriers in
      different sections of the sample is consistent with the theoretical calculation
      of local energy gaps. Quantitative analysis of the microscopy and transport data
      also reveals the linear dependence of photoconductivity on the laser intensity
      and the influence of interlayer coupling on carrier recombination. Combining
      theoretical modeling, atomic-scale imaging, mesoscale impedance microscopy, and
      device-level characterization, our work suggests an exciting perspective for
      controlling the intrinsic band gap variation in 2D heterostructures down to a
      regime of a few nanometers.

PMID- 30289265
TI  - Plagiochianins A and B, Two ent-2,3- seco-Aromadendrane Derivatives from the
      Liverwort Plagiochila duthiana.
AB  - Two novel ent-aromadendrane derivatives, plagiochianin A (1), possessing an
      unprecedented 2,3:6,7-di- seco-6,8-cyclo-aromadendrane carbon scaffold conjugated
      with three cyclic acetals, and plagiochianin B (2), an exceptional pyridine type
      aromadendrane alkaloid, were isolated from the Chinese liverwort Plagiochila
      duthiana. Their structures were established by comprehensive spectroscopic
      analysis coupled with single-crystal X-ray diffraction and electronic circular
      dichroism calculations. A plausible biogenetic pathway of these two compounds is
      presented, and their acetylcholinesterase inhibitory activities are preliminarily
      tested using TLC-bioautographic assays.

PMID- 30289266
TI  - A Ritter-Type Route to N-Benzylamides by Multicomponent Reaction Based on p
      (Trifluoromethyl)- p-quinols.
AB  - A novel multicomponent reaction of p-(trifluoromethyl)- p-quinolsilyl ethers,
      ketones, and nitriles was developed for the efficient synthesis of p
      trifluoromethylated N-benzylamides. The key step of the reaction involves the
      formation of an unstable condensation precursor in situ generated form the
      condensation of p-(trifluoromethyl)- p-quinolsilyl ethers with ketones. This work
      provides a significant expansion to the Ritter-type reaction, and the reaction
      can proceed under mild reaction conditions and tolerate various nitriles
      including both aryl and aliphatic nitriles.

PMID- 30289267
TI  - Eosinophilic Angiocentric Fibrosis: A Review and Update of Its Association With
      Immunoglobulin G4-Related Disease.
AB  - Eosinophilic angiocentric fibrosis is a rare indolent lesion of the head and neck
      region that has characteristic histologic findings of onionskin fibrosis and
      prominent eosinophils. Its pathogenesis has been poorly understood and has been
      most commonly attributed to hypersensitivity or previous trauma. Recently, the
      lesion has been included in the spectrum of immunoglobulin G4 (IgG4)-related
      disease. However, few of the existing cases of eosinophilic angiocentric fibrosis
      have been evaluated for IgG4+ and IgG+ plasma cells. Therefore, we provide an
      update on the clinical and histologic features of eosinophilic angiocentric
      fibrosis to increase awareness of the entity and encourage its further
      characterization as an IgG4-related disease.

PMID- 30289268
TI  - Comparing Spore Resistance of Bacillus Strains Isolated from Hydrothermal Vents
      and Spacecraft Assembly Facilities to Environmental Stressors and Decontamination
      Treatments.
AB  - Submarine hydrothermal vents are inhabited by a variety of microorganisms capable
      of tolerating environmental extremes, making them ideal candidates to further
      expand our knowledge of the limitations for terrestrial life, including their
      ability to survive the exposure of spaceflight-relevant conditions. The spore
      resistance of two Bacillus spp. strains, APA and SBP3, isolated from two shallow
      vents off Panarea Island (Aeolian Islands, Italy), to artificial and
      environmental stressors (i.e., UVC radiation, X-rays, heat, space vacuum,
      hydrogen peroxide [H2O2], and low-pressure plasma), was compared with that of two
      close phylogenetic relatives (Bacillus horneckiae and Bacillus oceanisediminis).
      Additional comparisons were made with Bacillus sp. isolated from spacecraft
      assembly facilities (B. horneckiae, Bacillus pumilus SAFR-032, and Bacillus
      nealsonii) and the biodosimetry strain and space microbiology model organism
      Bacillus subtilis. Overall, a high degree of spore resistance to stressors was
      observed for the strains isolated from spacecraft assembly facilities, with an
      exceptional level of resistance seen by B. pumilus SAFR-032. The environmental
      isolate SBP3 showed a more robust spore resistance to UVC, X-rays, H2O2, dry
      heat, and space vacuum than the closely related B. horneckiae. Both strains (SBP3
      and APA) were more thermotolerant than their relatives, B. horneckiae and B.
      oceanisediminis, respectively. SBP3 may have a novel use as a bacterial model
      organism for future interrogations into the potential of forward contamination in
      extraterrestrial environments (e.g., icy moons of Jupiter or Saturn), spacecraft
      sterilization and, broadly, microbial responses to spaceflight-relevant
      environmental stressors.

PMID- 30289269
TI  - Succinate Dehydrogenase Complex: An Updated Review.
AB  - Succinate dehydrogenase (SDH) is uniquely tasked with a dual role in the
      essential energy-producing processes of a cell. Although SDH subunits and
      assembly factors form part of the same enzyme complex, mutations in their
      respective genes lead to significantly different clinical phenotypes. Remarkable
      discoveries in the last 17 years have led to the delineation of the SDH complex
      deficiency syndrome and its multiple pathogenic branches. Here we provide an
      updated overview of SDH deficiency in order to raise awareness of its multiple
      connotations including nonneoplastic associations and pertinent features of the
      continually growing list of SDH-mutant tumors so as to better direct genetic
      counseling and predict prognosis.

PMID- 30289270
TI  - Evaluation of Bacterial Contamination in Goat Milk Powder Using PacBio Single
      Molecule Real-Time Sequencing and Droplet Digital PCR.
AB  - Goat milk powder is a nutritious and easy-to-store product that is highly favored
      by consumers. However, the presence of contaminating bacteria and their
      metabolites may significantly affect the flavor, solubility, shelf life, and
      safety of the product. To comprehensively and accurately understand the sanitary
      conditions in the goat milk powder production process and potential threats from
      bacterial contamination, a combination of Pacific Biosciences single molecule
      real-time sequencing and droplet digital PCR was used to evaluate bacterial
      contamination in seven goat milk powder samples from three dairies. Ten phyla,
      119 genera, and 249 bacterial species were identified. Bacillus, Paenibacillus,
      Lactococcus, and Cronobacter were the primary genera. Bacillus cereus,
      Lactococcus lactis, Alkaliphilus oremlandii, and Cronobacter sakazakii were the
      dominant species. With droplet digital PCR, 6.3 * 104 copies per g of Bacillus
      cereus and 1.0 * 104 copies per g of Cronobacter spp. were quantified, which may
      increase the risk of food spoilage and the probability of foodborne illness and
      should be monitored and controlled. This study offers a new approach for
      evaluating bacterial contamination in goat milk powder and supplies a reference
      for the assessment of food safety and control of potential risk, which will be of
      interest to the dairy industry.

PMID- 30289271
TI  - Sedentary time, metabolic abnormalities, and all-cause mortality after myocardial
      infarction: A mediation analysis.
AB  - Background Sedentary time was associated with myocardial infarction (MI) and
      metabolic diseases in previous studies. Purpose To investigate whether sedentary
      time measured before disease onset was associated with all-cause mortality among
      MI survivors and whether the sedentary time-mortality association was mediated by
      physical activity status and metabolic phenotypes. Methods In this prospective
      community-based cohort including 101,510 Chinese adults, we used sedentary time,
      evaluated at 2006 (baseline), to predict further all-cause mortality among
      individuals who then developed new onset MI from 2006 to December 2013 ( n =
      989). The post-MI mortality was ascertained after the first non-fatal MI until
      December 2014. We assessed the mediating effects of physical inactivity and
      metabolic factors on the sedentary time-mortality association. Results During 7
      years follow up, 180 deaths occurred among these participants with incident MI.
      Prolonged sedentary time was associated with a higher risk of mortality among MI
      survivors. The adjusted hazard ratio (HR) of mortality for sedentary time 4-8
      hours/day versus <4 hours/day, was 1.62 (95% confidence interval (CI) 1.14-2.31).
      A high amount of sedentary time (>4 hours/day) and inactive physical activity had
      an increased risk of all-cause mortality (HR: 2.74, 95% CI 1.34-5.60), relative
      to those with sedentary time <=4 hours/day and moderate/vigorous physical
      activity. Physical inactivity and metabolic factors mediated a small proportion
      (<=9.2 % for all) of the total association between sedentary time and post-MI
      mortality. Conclusion High sedentary time was significantly associated with all
      cause mortality among MI survivors, independent of physical activity status and
      metabolic abnormalities.

PMID- 30289272
TI  - Trends in incident acute myocardial infarction in Norway: Could the results be
      under- or overestimated?

PMID- 30289273
TI  - Effectiveness of different outreach strategies to identify individuals at high
      risk of diabetes in a heterogeneous population: a study in the Swedish
      municipality of Sodertalje.
AB  - BACKGROUND: Identifying type 2 diabetes mellitus (T2DM) is a prerequisite for the
      institution of preventive measures to reduce future micro and macrovascular
      complications. Approximately 50% of people with T2DM are undiagnosed, challenging
      the assumption that a traditional primary healthcare setting is the most
      efficient way to reach people at risk of T2DM. A setting of this kind may be even
      more suboptimal when it comes to reaching immigrants, who often appear to have
      inferior access to healthcare and/or are less likely to attend routine health
      checks at primary healthcare centres. OBJECTIVES: The objective of this study was
      to identify the best strategy to reach individuals at high risk of T2DM and
      thereby cardiovascular disease in a heterogeneous population. METHODS: All 18-65
      year-old inhabitants in the Swedish municipality of Sodertalje ( n~51,000)
      without known T2DM and cardiovascular disease were encouraged to complete the
      Finnish Diabetes Risk Score (FINDRISC: score > 15 indicating a high and > 20 a
      very high risk of future T2DM and cardiovascular disease) through the following
      communication channels: primary care centres, workplaces, Syrian orthodox
      churches, pharmacies, crowded public places, mass media, social media and mail.
      Data collection lasted for six weeks. RESULTS: The highest response rate was
      obtained through workplaces (27%) and the largest proportion of respondents at
      high/very high risk through the Syrian orthodox churches (18%). The proportion
      reached through primary care centres was 4%, of whom 5% were at elevated risk.
      The cost of identifying a person at elevated risk through the Syrian orthodox
      church was ?104 compared with ?8 through workplaces and ?112 through primary care
      centres. CONCLUSIONS: The choice of communication channels was important to reach
      high/very high-risk individuals for T2DM and for screening costs. In this
      immigrant-dense community, primary care centres were inferior to strategies using
      workplaces and churches in terms of both the proportion of identified at-risk
      individuals and costs.

PMID- 30289274
TI  - The yin and yang of light: A cardiovascular point of view.

PMID- 30289276
TI  - Environmental Data and Survival Data of Deinococcus aetherius from the Exposure
      Facility of the Japan Experimental Module of the International Space Station
      Obtained by the Tanpopo Mission.
AB  - The Tanpopo mission has two objectives: (1) test the panspermia hypothesis and
      (2) test whether organic compounds may have been transferred to Earth before the
      origin of life. We developed an exposure panel (EP) designed to expose microbes
      and organic compounds to the space environment and a capture panel designed to
      capture high-velocity particles on the International Space Station (ISS) using
      aerogel contained in an aluminum container. The panels returned after 1 year of
      exposure at the Exposure Facility of the Japan Experimental Module, ISS. In this
      communication, we report the measurements of temperature, radiation dosimeter and
      vacuum ultraviolet dosimeter in the EP, and survival data of Deinococcus
      aetherius. The environmental data are consistent with survival data of microbes
      and organic compounds, which will be presented elsewhere in detail.

PMID- 30289275
TI  - Return to Play and In-Game Performance Statistics Among Pitchers After Ulnar
      Collateral Ligament Reconstruction of the Elbow: A Systematic Review.
AB  - BACKGROUND: Injury to the ulnar collateral ligament of the elbow is relatively
      common among baseball pitchers. Ulnar collateral ligament reconstruction (UCLR)
      has revolutionized the management of this injury, allowing a greater proportion
      of pitchers to return to play. PURPOSE: To assess the return to play and in-game
      performance specific to baseball pitchers who have undergone primary UCLR. STUDY
      DESIGN: Systematic review. METHODS: This review was conducted according to the
      PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta
      Analyses). The electronic databases MEDLINE, EMBASE, and PubMed were searched for
      relevant studies, and pertinent data were abstracted. Only studies reporting in
      game performance statistics (earned run average [ERA], pitching velocity, innings
      pitched per season, etc) of pitchers after UCLR were included. The methodological
      index for nonrandomized studies (MINORS) was used to assess study quality.
      RESULTS: A total of 14 studies and 1520 pitchers were included in this systematic
      review. All studies were of level 3 or 4 evidence, and the mean +/- SD MINORS
      score was 14.4 +/- 3.0, which indicates fair quality of evidence for
      nonrandomized studies. The rates of return to any level of pitching after UCLR
      ranged from 79% to 100%. Subgroup analysis revealed that 79% to 87% of Major
      League Baseball (MLB) pitchers returned to preinjury levels of pitching. The mean
      time to return to play was 19.8 +/- 13.5 months, and the mean time to return to
      competition for MLB pitchers was 17.3 +/- 2.4 months. Of the 5 studies reporting
      ERA, 2 cited a significant increase after UCLR, and 1 indicated a significant
      decrease. Of the 4 studies reporting fastball velocity, 3 cited decreased
      pitching velocities after UCLR. All studies found that pitchers pitched, on
      average, fewer innings per game or season after UCLR. CONCLUSION: There was a
      high rate of return to pitching after UCLR. However, most studies showed that
      UCLR was associated with a prolonged recovery and significant decline in pitching
      performance as objectively measured by in-game statistics. The strength of these
      conclusions is limited by the quality of the available literature and
      inconsistencies in the reporting of outcomes.

PMID- 30289277
TI  - Assessment of radiation dose from radon ingestion and inhalation in commercially
      bottled drinking water and its annual effective dose in Eastern Province, Saudi
      Arabia.
AB  - The isotopes of radium, uranium, polonium, lead, and short-lived radon are the
      common radionuclides found in drinking water. The abnormal amount of radon in
      drinking water causes health risks. In this study, an attempt has been made to
      estimate the level of radon concentrations and its annual effective dose from
      bottled water brands and tap drinking water. A total of 77 samples of drinking
      water sources; 47 bottled water brands and 27 tap water samples including 3
      samples from water storage tank supplier were collected and examined. The
      measurements were performed using active detection method technique called
      Durridge RAD7-H2O with closed loop. The minimum and maximum level of average
      radon concentrations was 0.10 +/- 0.02 BqL-1 and 9.2 +/- 0.02 BqL-1. The results
      were below the limit recommended by the Environmental Protection Agency (11 BqL
      1). The annual effective dose for children and adults was in the range from
      almost 0.51 uSvy-1 to 46.69 uSvy-1. There are no indications of significant
      threat from radon concentrations in bottled water brands or tap drinking water,
      and it is safe as far as health hazard is concerned.

PMID- 30289279
TI  - Paleolakes of Northeast Hellas: Precipitation, Groundwater-Fed, and Fluvial Lakes
      in the Navua-Hadriacus-Ausonia Region, Mars.
AB  - The slopes of northeastern Hellas Basin, Mars exhibit a wide variety of fluvial
      landforms. In addition to the Dao-Niger-Harmakhis-Reull Valles outflow channels,
      many smaller channels and valleys cut into this terrain, several of which include
      discontinuous sections. We have mapped these channels and channel-associated
      depressions to investigate potential paleolakes from the Navua Valles in the
      West, through the Hadriacus Mons volcano in the center, to the Ausonia Montes in
      the East. We have identified three groups of candidate paleolakes at the source
      regions of major drainages and a fourth paleolake type scattered along the lower
      reaches of these drainages. Each paleolake group has a distinct character,
      determined by different formative processes, including precipitation and
      groundwater for lakes at the channel sources, and fluvially transported water at
      the lower channel reaches. Only one of these 34 basins had been cataloged
      previously in paleolake basin databases. Several of these sites are at proximity
      to the Hadriacus volcanic center, where active dikes during the Hesperian could
      have produced hydrothermal systems and habitable environments. Deposits within
      these paleolake depressions and at the termini of channels connected to these
      candidate paleolakes contain the geological and potentially biological record of
      these environments.

PMID- 30289278
TI  - Altered Functional Connectivity of the Executive Functions Network During a
      Stroop Task in Children with Reading Difficulties.
AB  - Children with reading difficulties (RDs) often receive related accommodations in
      schools, such as additional time for examinations and reading aloud written
      material. Existing data suggest that these readers share challenges in executive
      functions (EFs). Our study was designed to determine whether children with RDs
      have specific challenges in EFs and define neurobiological signatures for such
      difficulties using magnetic resonance imaging (MRI) data. Reading and EFs
      abilities were assessed in 8-12-year-old children with RDs and age-matched
      typical readers. Functional MRI data were acquired during a Stroop task, and
      functional connectivity of the EFs defined network was calculated in both groups
      and related to reading ability. Children with RDs showed lower reading and EFs
      abilities and demonstrated greater functional connectivity between the EFs
      network and visual, language, and cognitive control regions during the Stroop
      task, compared to typical readers. Our results suggest that children with RDs
      utilize neural circuits supporting EFs more so than do typical readers to perform
      a cognitive task. These results also provide a neurobiological explanation for
      the challenges in EFs shared by children with RDs and explain challenges this
      group shares outside of the reading domain.

PMID- 30289280
TI  - Altered Functional Connectivity Observed at Rest in Children and Adolescents
      Prenatally Exposed to Alcohol.
AB  - Studies of brain structure in fetal alcohol spectrum disorder (FASD) have shown
      the global and focal effects that prenatal alcohol exposure (PAE) has on the
      brain, suggesting but not measuring altered function in FASD. This study aimed to
      (1) identify resting-state functional networks in children and adolescents with
      FASD, (2) investigate functional connectivity differences compared with healthy
      controls, and (3) assess the links to cognitive deficits. Participants included
      66 children/adolescents with FASD (aged 5.5-18.9 years) and 67 healthy controls
      (aged 5.8-18.5 years) scanned across four sites as part of the NeuroDevNet study.
      Six core functional networks with 27 regions of interest (ROIs) were examined
      using seed-based and ROI-to-ROI analyses. Average seed-based connectivity maps
      showed significant spatial overlap of positively correlated regions for all six
      core networks between FASD and controls, but there was less overlap for
      negatively correlated regions. ROI-to-ROI matrices demonstrated lower
      internetwork connectivity between regions primarily associated with the salience
      network (anterior cingulate cortex and bilateral insula), frontal-parietal
      network (bilateral posterior parietal cortex), and language network (right
      posterior superior temporal gyrus). Post hoc correlations of the FASD
      participants without medication revealed a relationship between functional
      connectivity and performance on two cognitive tests associated with mathematics
      ability and attention. Even though participants with PAE exhibit very similar
      intranetwork functional connectivity patterns as controls, their lower
      internetwork functional connectivity suggests underlying deficits in the
      functional network brain architecture that may be related to cognitive
      impairment.

PMID- 30289281
TI  - Evaluation of Common Variants in Matrix Metalloproteinase-9 Gene with Lumbar Disc
      Herniation in Han Chinese Population.
AB  - OBJECTIVE: Lumbar disc herniation (LDH) is a common and frequent orthopedic
      disease with strong genetic determinants. The disruption of the intervertebral
      disc extracellular matrix has been found to play a key role in the development of
      LDH, suggesting that abnormal matrix metalloproteinases (MMPs) may promote the
      degradation of the disc matrix. MMP-9, an important member of the MMP family, is
      a good candidate for the LDH susceptibility gene. The present study aimed to
      investigate the association of common variants in the MMP-9 gene with the risk,
      severity, and clinical characteristic variables of LDH. MATERIALS AND METHODS:
      Fourteen tag single nucleotide polymorphisms (SNPs) entirely covering the region
      of the MMP-9 gene were analyzed in a sample of 845 patients and 1751 healthy
      controls. RESULTS: The SNP rs17576 was found to be significantly associated with
      susceptibility to LDH (OR = 0.77, p = 0.0002), which was also confirmed by
      haplotype-based analyses (rs79845319-rs17576-rs45437897, global p < 0.001). Our
      results indicated that the A allele of rs17576 reduced the risk of LDH by ~23% on
      average. Furthermore, the G allele of rs17576 was found to correlate with more
      severe grades of disc degeneration. CONCLUSION: Our results provide additional
      evidence supporting an important role of the MMP-9 gene in the pathogenesis of
      LDH.

PMID- 30289282
TI  - Immunoregulatory effects of indole-3-carbinol on monocyte-derived macrophages in
      systemic lupus erythematosus: A crucial role for aryl hydrocarbon receptor.
AB  - Macrophages are versatile phagocytic cells in immune system with immunoregulatory
      functions. However, the removal of apoptotic cells by macrophages is disturbed in
      systemic lupus erythematosus (SLE). Aryl hydrocarbon receptor (AhR) is a ligand
      activated cytoplasmic receptor and transcription factor with diverse effects on
      immune response. Indole-3-carbinol (I3C) is an AhR agonist which has been
      implicated as a beneficial factor in regulating inflammation and cytokine
      expression in murine models of SLE. However, the molecular mechanisms are not
      thoroughly studied. Here, we aimed to investigate the ex vivo effects of I3C on
      polarization of monocyte-derived macrophages (MDMs) in SLE patients and the
      expression of regulatory cytokines upon AhR activation. MDMs from 15 newly
      diagnosed SLE patients and 10 normal subjects were induced by Jurkat apoptotic
      bodies (JABs) and treated with I3C. I3C enhanced the nuclear accumulation of AhR
      among MDMs of SLE patients and altered the expression of AhR target genes
      including CYP1A1, IL1- beta, IDO-1 and MRC-1. The imbalanced expression of pro-
      and anti- inflammatory cytokines (IL-10, IL-12, TGFbeta1, TNFalpha, IL-23, IL-6
      and IFN-gamma) was compensated in response to I3C. AhR activation was also
      associated with the overexpression of M2 markers (CD163) and downregulation of M1
      markers (CD86). Thus, macrophages are activated alternatively in response to I3C.
      The obtained data indicate that I3C-mediated AhR activation possess
      immunoregulatory effects on macrophages of SLE patients by exerting an obvious
      downregulation in the expression of pro-inflammatory and overexpression of anti
      inflammatory cytokines. Therefore, AhR could be targeted and further investigated
      as a choice of anti-inflammatory therapies for autoimmune disorders such as SLE.

PMID- 30289283
TI  - A Systematic Review of the Outcomes Used to Assess Upper Body Lymphedema.
AB  - PURPOSE: To ascertain how change in upper body lymphedema is assessed and
      understand how clinically significant change is determined. METHOD: A systematic
      search of the literature resulted in 55 eligible studies for analysis. RESULTS: A
      range of assessment methods, measurement protocols, and outcomes were used in the
      literature. Of the 21 studies in which thresholds for change were set a priori,
      20 different thresholds were reported. CONCLUSION: How data was measured,
      analysed and reported was inconsistent across studies. Consensus on a core
      outcome set with standardised assessment protocols and reporting; and
      investigation into empirically based minimum important differences (MID) is
      needed.

PMID- 30289284
TI  - Effect of poly (l-lactic acid) scaffolds seeded with aligned diaphragmatic
      myoblasts overexpressing connexin-43 on infarct size and ventricular function in
      sheep with acute coronary occlusion.
AB  - Diaphragmatic myoblasts (DM) are stem cells of the diaphragm, a muscle displaying
      high resistance to stress and exhaustion. We hypothesized that DM modified to
      overexpress connexin-43 (cx43), seeded on aligned poly (l-lactic acid) (PLLA)
      sheets would decrease infarct size and improve ventricular function in sheep with
      acute myocardial infarction (AMI). Sheep with AMI received PLLA sheets without DM
      (PLLA group), sheets with DM (PLLA-DM group), sheets with DM overexpressing cx43
      (PLLA-DMcx43) or no treatment (control group, n = 6 per group). Infarct size
      (cardiac magnetic resonance) decreased ~25% in PLLA-DMcx43 [from 8.2 +/- 0.6 ml
      (day 2) to 6.5 +/- 0.7 ml (day 45), p < .01, ANOVA-Bonferroni] but not in the
      other groups. Ejection fraction (EF%) (echocardiography) at 3 days post-AMI fell
      significantly in all groups. At 45 days, PLLA-DM y PLLA-DMcx43 recovered their
      EF% to pre-AMI values (PLLA-DM: 61.1 +/- 0.5% vs. 58.9 +/- 3.3%, p = NS; PLLA
      DMcx43: 64.6 +/- 2.9% vs. 56.9 +/- 2.4%, p = NS), but not in control (56.8 +/-
      2.0% vs. 43.8 +/- 1.1%, p < .01) and PLLA (65.7 +/- 2.1% vs. 56.6 +/- 4.8%, p <
      .01). Capillary density was higher (p < .05) in PLLA-DMcx43 group than in the
      remaining groups. In conclusion, PLLA-DMcx43 reduces infarct size in sheep with
      AMI. PLLA-DMcx43 and PLLA-DM improve ventricular function similarly. Given its
      safety and feasibility, this novel approach may prove beneficial in the clinic.
      [Formula: see text].

PMID- 30289285
TI  - Ubiquitin Associated and SH3 Domain Containing B (UBASH3B) Gene Association with
      Behcet's Disease in Iranian Population.
AB  - PURPOSE: To evaluate the possible association of UBASH3B gene rs4936742 (T > C)
      polymorphism with Behcet's disease (BD) and posterior uveitis in BD. MATERIALS
      AND METHODS: One hundred and thirty-one patients with BD (51 Behcet's posterior
      uveitis and 80 non-ocular Behcet's patients) and 61 unrelated age-matched healthy
      individuals as a control group without any inflammatory disease were selected.
      All BD cases were under follow-up and treatment in uveitis or rheumatology
      clinics for at least 5 years. All research subjects, including control
      individuals, received a comprehensive rheumatologic evaluation. All patients and
      controls were genotyped for UBASH3B rs4936742 (T > C) polymorphism by PCR-RFLP
      technique. RESULTS: The observed frequencies of genotypes were significantly
      different among patients and controls (19.7% versus 30.5% for TT, OR = 2.9, P =
      0.011 and 36.1% versus 45.8% for CT, OR = 2.38, P = 0.017). Frequencies of T
      allele showed significantly higher values in Behcet's patients (OR = 1.9, P =
      0.004). Subgroup genotypic and allelic analyses disclosed no significant
      difference between Behcet's posterior uveitis and control groups, neither between
      Behcet's posterior uveitis and non-ocular BD groups. However, genotypic and
      allelic analyses between non-ocular BD and control groups revealed statistically
      significant difference (36.3% versus 19.7% for TT, OR = 4.08, P = 0.003 and 43.8%
      versus 36.1% for CT, OR = 2.68, P = 0.018, 58.1% versus 37.7% for T allele, OR =
      2.29, P = 0.001). Individuals carrying the TT genotype for UBASH3B were four
      times more likely to develop non-ocular BD than unaffected, control individuals.
      CONCLUSION: Our results showed that the UBASH3B gene rs4936742 (T > C)
      polymorphism is associated with an increased risk of Behcet's disease, especially
      non-ocular BD, in Iranian population. We could not find any susceptibility role
      of this genetic locus for posterior uveitis in Behcet's disease.

PMID- 30289286
TI  - Trust, Sexual Trust, and Sexual Health: An Interrogative Review.
AB  - Trust is experienced almost constantly in all forms of social and interpersonal
      relationships, including sexual relationships, and may contribute both directly
      and indirectly to sexual health. The purpose of this review is to link three
      aspects of trust to sexual health: (1) the role of trust in sexual relationships;
      (2) the role of trust in sexually transmitted infection (STI) prevention,
      particularly condom use; and (3) the relevance of trust in sexual relationships
      outside of the traditional model of monogamy. The review ends with consideration
      of perspectives that could guide new research toward understanding the enigmas of
      trust in partnered sexual relations in the context of sexual and public health.

PMID- 30289287
TI  - A randomized double-blind parallel-group phase III study to compare the efficacy
      and safety of NI-071 and infliximab reference product in Japanese patients with
      active rheumatoid arthritis refractory to methotrexate.
AB  - OBJECTIVES: This study aimed to demonstrate the equivalence of NI-071, an
      infliximab biosimilar (BS), and the infliximab reference product (RP) for
      treating Japanese patients with active rheumatoid arthritis (RA) refractory to
      methotrexate. METHODS: In this multicenter two-period phase III study, patients
      were treated with BS or RP for 30 weeks (Period I) in a randomized double-blind
      manner and then with BS for the following 24 weeks (Period II). The efficacy and
      safety of BS and RP were compared. RESULTS: The disease activity score in 28
      joint count based on erythrocyte sedimentation rate or C-reactive protein and the
      American College of Rheumatology 20/50/70-based efficacy profiles of BS were
      similar to those of RP during Period I (30 weeks) including evaluations at Week
      14, a critical time point. BS efficacy was maintained throughout the 54-week
      study period. BS efficacy profile matched the RP profile until Week 54 after the
      drug switch from RP to BS at Week 30. The safety profiles of BS and RP were
      comparable and the long-term safety of BS was confirmed. CONCLUSIONS: BS
      demonstrated equivalent efficacy and safety to RP at treatment weeks 14 and 30,
      and long-term safety until Week 54 in Japanese RA patients.

PMID- 30289288
TI  - CORRECTION.

PMID- 30289289
TI  - Biomarkers for acute radiation syndrome: challenges for developing radiation
      countermeasures following animal rule.

PMID- 30289290
TI  - Managing Acute Insomnia in Prison: Evaluation of a "One-Shot" Cognitive
      Behavioral Therapy for Insomnia (CBT-I) Intervention.
AB  - OBJECTIVES/BACKGROUND: Insomnia is a serious condition that affects over 60% of
      the prison population and has been associated with aggression, anger,
      impulsivity, suicidality, and increased prison health care use.
      Nonpharmacological interventions for prison inmates are scarce despite the high
      prevalence and significant consequences of insomnia among those incarcerated. The
      aim of the present study was to examine the preliminary efficacy and
      effectiveness of a one-shot session of cognitive behavioral therapy for insomnia
      (CBT-I) for prison inmates with acute insomnia in an open trial.
      Method/Participants: The intervention consisted of one 60-70 min session of CBT-I
      and a self-management pamphlet. A consecutive series of 30 adult male offenders
      with acute insomnia from a UK prison completed measures of prospective sleep
      (daily sleep diary), insomnia symptoms severity (Insomnia Severity Index), and
      mood symptoms (Patient Health Questionnaire and General Anxiety Disorder) one
      week before and four weeks after receiving the intervention. RESULTS: Pairwise t
      tests revealed that a single shot of CBT-I was effective in reducing the severity
      of insomnia in adult male offenders (t = [29], 12.65, p < 0.001). Further, the
      results demonstrated moderate to large effect sizes for reductions in depressive
      (dRM = 0.77) and anxious (dRM = 0.83) symptoms, as well as insomnia severity (dRM
      = 2.35). CONCLUSIONS: A single-shot session of CBT-I is effective in managing
      acute insomnia and mood (depression, anxiety) symptoms in adult male prison
      inmates. Future research should focus on testing if the single-shot CBT-I
      intervention can be implemented and disseminated in other settings and
      populations (e.g., female and juvenile or youth offenders).

PMID- 30289291
TI  - Adaptive radiotherapy for head and neck cancer.
AB  - INTRODUCTION: Large anatomical variations can be observed during the treatment
      course intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC),
      leading to potential dose variations. Adaptive radiotherapy (ART) uses one or
      several replanning sessions to correct these variations and thus optimize the
      delivered dose distribution to the daily anatomy of the patient. This review,
      which is focused on ART in the HNC, aims to identify the various strategies of
      ART and to estimate the dosimetric and clinical benefits of these strategies.
      MATERIAL AND METHODS: We performed an electronic search of articles published in
      PubMed/MEDLINE and Science Direct from January 2005 to December 2016. Among a
      total of 134 articles assessed for eligibility, 29 articles were ultimately
      retained for the review. Eighteen studies evaluated dosimetric variations without
      ART, and 11 studies reported the benefits of ART. RESULTS: Eight in silico
      studies tested a number of replanning sessions, ranging from 1 to 6, aiming
      primarily to reduce the dose to the parotid glands. The optimal timing for
      replanning appears to be early during the first two weeks of treatment. Compared
      to standard IMRT, ART decreases the mean dose to the parotid gland from 0.6 to 6
      Gy and the maximum dose to the spinal cord from 0.1 to 4 Gy while improving
      target coverage and homogeneity in most studies. Only five studies reported the
      clinical results of ART, and three of those studies included a non-randomized
      comparison with standard IMRT. These studies suggest a benefit of ART in regard
      to decreasing xerostomia, increasing quality of life, and increasing local
      control. Patients with the largest early anatomical and dose variations are the
      best candidates for ART. CONCLUSION: ART may decrease toxicity and improve local
      control for locally advanced HNC. However, randomized trials are necessary to
      demonstrate the benefit of ART before using the technique in routine practice.

PMID- 30289292
TI  - Potential Pitfalls in Analyzing Structural Uncoupling of Endothelial NO Synthase:
      Aging is Not Associated with Increased Enzyme Monomerization.
AB  - Homodimer formation is essential for the normal activity of endothelial NO
      synthase (eNOS). Structural uncoupling of eNOS with generation of enzyme monomers
      is thought to contribute to endothelial dysfunction in several vascular disorders
      including aging. However, published reports on healthy arteries using low
      temperature SDS-PAGE has revealed considerable variation between studies in the
      relative expression of eNOS dimers and monomers. While assessing structural
      uncoupling of eNOS in aging arteries, we identified methodological pitfalls that
      might contribute to such variation. Experiments therefore investigated optimal
      approaches for analyzing expression of eNOS monomers and dimers, using human
      cultured aortic endothelial cells and aortas from young and aged F344 rats. The
      results demonstrate that published differences in treatment of cellular lysates
      can significantly impact the relative expression of several eNOS species
      including denatured monomers, partially-folded monomers, dimers and higher-order
      oligomers. In aortas, experiments initially confirmed a large increase in eNOS
      monomers in aging arteries, consistent with structural uncoupling. However, these
      monomers were actually endogenous IgG, which under these conditions has similar
      mobility to eNOS monomers. Increased IgG levels in aged aortas likely reflect the
      aging-induced disruption of endothelial junctions and increased arterial
      penetration of IgG. After removing the IgG signal, there was low levels of eNOS
      monomers in young arteries, which were not significantly different in aged
      arteries. Therefore, structural uncoupling of eNOS is not a prominent feature in
      young healthy arteries and the process is not increased by aging. The study also
      identifies optimal approaches to analyze eNOS dimers and monomers.

PMID- 30289293
TI  - Sex-specific effects of advanced maternal age on cardiovascular function in aged
      adult rat offspring.
AB  - Pregnancy at an advanced maternal age has an increased risk of complications for
      both the mothers and their offspring. We have previously shown that advanced
      maternal age in a rat model leads to poor fetal outcomes, maternal vascular
      dysfunction and hypertension, concordant with findings in humans. Moreover,
      offspring from aged dams had sex-specific cardiovascular dysfunction in young
      adulthood. Yet, the detrimental impact of aging on the cardiovascular system of
      the offspring in this model is unknown. We hypothesized that offspring born to
      aged dams (9.5-10 months old) would have impaired cardiovascular function at 12
      months of age. Echocardiographic data revealed signs of mild left ventricular
      (LV) diastolic dysfunction in only male offspring from aged dams (Isovolumetric
      relaxation time (IVRT); young 34.27+/-2.04 vs. aged dam 27.61+/-0.99 msec; P<0.01
      and E'/A'; young 1.08+/-0.04 vs. aged dam 0.96+/-0.02; P<0.05). In young
      adulthood (4 months of age), we previously showed that male, but not female,
      offspring born from aged dams had impaired recovery from ischemia/reperfusion
      (I/R) injury. Aging did not alter the susceptibility of female offspring to I/R
      injury. Interestingly, wire myography data revealed that male offspring from aged
      dams had enhanced vascular sensitivity to methacholine (MCh pEC50: young 7.4+/
      0.08 vs. aged dam 7.9+/-0.11; P=0.007) due, in part, to increased prostaglandin
      mediated vasodilation. Despite intact endothelium-dependent relaxation, female
      offspring from aged dams had elevated systolic blood pressure (young 125.3+/-4.2
      mmHg vs. aged dam 144.0+/-6.9 mmHg, P=0.03). These data highlight sex-specific
      mechanisms underlying cardiovascular programming in offspring born to dams of
      advanced age.

PMID- 30289294
TI  - Sex Differences in the Central and Peripheral Manifestations of Ischemia-induced
      Heart Failure in Rats.
AB  - Sex differences in the presentation, outcome and responses to treatment of
      systolic heart failure (HF) have been reported. We examined the effect of sex on
      central neural mechanisms contributing to neurohumoral excitation and its
      peripheral manifestations in HF rats. Male and female SD rats underwent coronary
      ligation (CL) to induce HF. Age-matched rats served as controls. Infarct size and
      left ventricular function were similar 24 hours and 4 weeks after CL. Female HF
      rats had a lower mortality rate and less hemodynamic compromise, pulmonary
      congestion and right ventricular remodeling 4 weeks after CL. Plasma angiotensin
      II (ANG II), arginine vasopressin (AVP) and norepinephrine levels were increased
      in HF rats in both sexes, but AVP and norepinephrine levels increased less in
      females. In hypothalamic paraventricular nucleus, a key cardiovascular-related
      nucleus contributing to neurohumoral excitation in HF, mRNA levels for the pro
      inflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta,
      cyclooxygenase-2, and the ANG II type 1a receptor were increased in HF rats of
      both sexes, but less so in females. Angiotensin converting enzyme 2 protein
      increased in female HF rats but decreased in male HF rats. AVP mRNA was lower in
      both control and HF females, compared with the respective males. ERK1/2 activity
      increased similarly in both sexes in HF. The results suggest that female HF rats
      have less central neural excitation and less associated hemodynamic compromise
      than male HF rats with the same degree of initial ischemic cardiac injury.

PMID- 30289295
TI  - ENDOCRINOLOGY FELLOWS' PERCEPTION OF THEIR CONFIDENCE AND SKILL LEVEL IN
      PROVIDING TRANSGENDER HEALTHCARE.
AB  - OBJECTIVE: Both educational content and hours devoted to transgender health
      training of endocrinology fellows are suboptimal. The objective of this study was
      to assess the perspectives of endocrinology fellows on their training in
      transgender health. METHODS: We evaluated the state of comfort and knowledge of
      transgender healthcare among endocrinology fellows attending Endocrine
      University. Pre- and post-surveys were administered to fellows following
      participation in a case-based session on transgender health. RESULTS: The
      majority of fellows felt that training in transgender health is important (95.9%
      189/197); however only 58.9% reported inclusion of dedicated transgender content
      in their training programs. Fellows who had received transgender healthcare
      education, and those who had seen more transgender patients in their training,
      were more likely to be confident in treating patients with hormone therapy
      (P<0.001 and p<0.0001, respectively). Following the case-based session, 62.4 % of
      fellows reported that they would change their practice, 72.8% felt that their
      comfort level with transgender care had improved, and 91% felt that transgender
      content such as that provided in the educational session should be mandatory in
      endocrinology training programs. Methods most desired by fellows to improve their
      education included lectures from visiting professors (70.3%), participation in
      elective rotations (62.1%), online training modules (57.9%), and attendance at
      meetings with transgender topics (57.4%). CONCLUSION: Transgender health
      education of US endocrinology fellows is suboptimal. Participation in a case
      based session significantly increased the comfort level of endocrinology fellows
      in key areas of transgender health. ABBREVIATIONS: ACGME = Accreditation Council
      for Graduate Medical Education; AACE = American Association of Clinical
      Endocrinologist; AAMC = Association of American Medical Colleges; LGBT = Lesbian
      Gay Bisexual Transgender.

PMID- 30289296
TI  - VISUAL VIGNETTE.

PMID- 30289297
TI  - A TALE WITH AN INFILTRATIVE TWIST: TWO WRONGS MAKE A RIGHT?

PMID- 30289298
TI  - THE CLINICAL PRESENTATION OF PRIMARY HYPERPARATHYROIDISM: A SOUTHERN EUROPEAN
      PERSPECTIVE OVER THE LAST TWO DECADES.
AB  - BACKGROUND: The clinical presentation of primary hyperparathyroidism (PHPT) has
      changed widely in developed countries in the last few decades. We evaluated its
      variations in our series over a 20-year period, i.e. 1997-2016. PATIENTS: A
      retrospective survey was conducted in our series of 364 well-characterized
      consecutive patients, arbitrarily divided into four consecutive 5-year periods at
      diagnosis. RESULTS: In the overall series, only eGFR and urinary calcium showed a
      significant upward trend (p=0.032 and 0.039, respectively), whereas demographic
      and clinical characteristics were stable. The urinary calcium upward trend was
      confirmed also for the subgroup of symptomatic patients (p=0.013). No difference
      was observed in the demographic, clinical and biochemical characteristics of
      asymptomatic patients, or in the fraction of patients meeting surgical criteria.
      CONCLUSIONS: Clinical presentation of PHPT was stable over 20 years in our large
      series. ABBREVIATIONS: 25OHD = 25-hydroxy-vitamin D; DXA = dual X-ray
      absorptiometry; eGFR = estimated glomerular filtration rate; F = female; M =
      male; NHS = National Health System; PHPT = primary hyperparathyroidism; PTH =
      parathyroid hormone; UCa = urinary calcium; US = ultrasound.

PMID- 30289299
TI  - PRIMARY HYPERPARATHYROIDISM IN THE YOUNG: COMPARISON WITH THE ADULT PRIMARY
      HYPERPARATHYROIDISM.
AB  - OBJECTIVES: Primary hyperparathyroidism (PHPT) is relatively common among adults;
      however, rarely encountered in children and adolescents. According to the western
      literature, young PHPT is different from adult PHPT and is associated with more
      severe hypercalcaemia. PHPT in adult Indian population is different from its
      western counterpart. Here we present the clinical, biochemical and surgical
      characteristics of young PHPT from our tertiary care centre. METHODS: PHPT
      patients were divided into adult (age >=25 years) and young (age <25 years) PHPT
      groups. The clinical, biochemical, hormonal, histopathological characteristics
      and treatment outcome of young PHPT patients were compared with adult PHPT
      patients. RESULTS: Out of total 358 patients, 47 patients were young and 311
      patients were adult PHPT. The mean age of young and adult patients were19+/-4 and
      45+/-12 years, respectively; with female to male ratio of 1.24:1 and 3.38:1,
      respectively (p<0.05). The nature and frequency of presenting symptoms were
      comparable between the two groups. The most common symptom in young PHPT was bone
      pain, and was not significantly different from adults (57% vs. 61%,
      respectively). While, the most common symptom in adult PHPT was fatigue, which
      was also not significantly different from young patients (63% vs. 53%
      respectively), The serum calcium, phosphate, 25(OH)D, ALP Z-score and PTH levels
      were comparable between the two groups. Parathyroid adenoma was the commonest
      histopathological finding, while hyperplasia was rare in both the groups.
      CONCLUSIONS: In this series of young PHPT, we observed that young PHPT is not
      much different from adult counterpart in Indian scenario. ABBREVIATIONS: ALP =
      Alkaline phosphatase; Ca = Calcium; Cr = Creatinine; iPTH = Intact parathyroid
      hormone; MEN1 = Type 1 multiple endocrine neoplasia; MIBI = Methoxy Iso Butyl
      Isonitrile; P = Phosphate; PHPT = Primary hyperparathyroidism; PTH = Parathyroid
      hormone; RIPA = Right inferior parathyroid adenoma; PTH = Parathyroid hormone;
      RIPA = Right inferior parathyroid adenoma; 99mTc sestamibi = Technetium
      sestamibi; USG = Ultrasonography; 25(OH)D = 25-hydroxy vitamin D.

PMID- 30289300
TI  - MANAGEMENT OF THYROTOXICOSIS: PRECONCEPTION, PREGNANCY, AND THE POSTPARTUM
      PERIOD.
AB  - OBJECTIVE: To review the diagnosis and management of thyrotoxicosis in women who
      are preconception, pregnant, and in the postpartum period. METHODS: Literature
      review of English-language papers published 1980-2018. RESULTS: Overt
      thyrotoxicosis occurs in 0.2% of pregnancies and subclinical thyrotoxicosis in
      2.5%. Hyperthyroidism in women of childbearing age most frequently is caused by
      Graves' disease. Gestational thyrotoxicosis, transient hCG-mediated
      hyperthyroidism, may develop in the first trimester of pregnancy. In the first
      year following delivery, postpartum thyroiditis, which frequently includes a
      thyrotoxic phase, occurs in 5% of women. Hyperthyroidism from nodular autonomy is
      uncommon in women of childbearing age. It is essential to understand the
      underlying etiology for thyrotoxicosis in order to recommend appropriate
      treatment. Gestational thyrotoxicosis requires supportive care, without anti
      thyroid drug therapy. Graves' disease may be treated with anti-thyroid drugs,
      radioactive iodine, or thyroidectomy. Pregnancy, plans for pregnancy, and
      lactation have important implications for the choice of Graves' disease
      treatment. When thyrotoxicosis presents following delivery, postpartum
      thyroiditis must be differentiated from Graves' disease. CONCLUSION: The
      diagnosis and management of thyrotoxicosis in the peri-pregnancy period present
      specific challenges. In making management decisions it is essential to weigh the
      risks and benefits of treatments not just for the mother but also for the fetus,
      and for breastfed infants. A team approach to management, with close
      collaboration between endocrinologists, maternal-fetal medicine specialists, and
      neonatologists, is essential. ABBREVIATIONS: hCG = human chorionic gonadotropin;
      MMI = methimazole; PPT = postpartum thyroiditis; PTU = propylthiouracil; T3 =
      triiodothyronine; T4 = thyroxine; TBG = thyroxine binding globulin; TBII = TSH
      receptor-binding inhibitory immunoglobulin; TRAb = TSH receptor antibody; TSH =
      thyroid stimulating hormone; TSI = thyroid stimulating immunoglobulin.

PMID- 30289301
TI  - WHY TAKE THE RISK? WE ONLY LIVE ONCE - THE DANGERS ASSOCIATED WITH NEGLECTING A
      PREOPERATIVE ALPHA ADRENOCEPTOR BLOCKADE IN PHEOCHROMOCYTOMA PATIENTS.

PMID- 30289302
TI  - PROACTIVE PROTOCOL-BASED MANAGEMENT OF HYPERGLYCEMIA AND DIABETES IN COLORECTAL
      SURGERY PATIENTS.
AB  - OBJECTIVE: The management of diabetic patients undergoing elective abdominal
      surgery continues to be unsystematic, despite evidence that standardized
      perioperative glycemic control is associated with fewer postoperative surgical
      complications. We examined the efficacy of a pre-operative diabetes optimization
      protocol implemented at a single institution in improving perioperative glycemic
      control with a target blood glucose of 80 to 180 mg/dL. METHODS: Patients with
      established and newly diagnosed diabetes who underwent elective colorectal
      surgery were included. The control group comprised 103 patients from January 1,
      2011, through December 31, 2013, before protocol implementation. The glycemic
      optimized group included 96 patients following protocol implementation from
      January 1, 2014, through July 31, 2016. Data included demographic information,
      blood glucose levels, insulin doses, hypoglycemic events, and clinical outcomes
      (length of stay, re-admissions, complications, and mortality). RESULTS: Patients
      enrolled in the glycemic optimization protocol had significantly lower glucose
      levels intra-operatively (145.0 mg/dL vs. 158.1 mg/dL; P = .03) and
      postoperatively (135.6 mg/dL vs. 145.2 mg/dL; P = .005). A higher proportion of
      patients enrolled in the protocol received insulin than patients in the control
      group (0.63 vs. 0.48; P = .01), but the insulin was administered less frequently
      (median [interquartile range] number of times, 6.0 [2.0 to 11.0] vs. 7.0 [5.0 to
      11.0]; P = .04). Two episodes of symptomatic hypoglycemia occurred in the control
      group. There was no difference in clinical outcomes. CONCLUSION: Improved peri
      operative glycemic control was observed following implementation of a
      standardized institutional protocol for managing diabetic patients undergoing
      elective colorectal surgery. ABBREVIATIONS: HbA1c = glycated hemoglobin A1c; IQR
      = interquartile range.

PMID- 30289303
TI  - VISUAL VIGNETTE.

PMID- 30289304
TI  - PITUITARY EVALUATION IN PATIENTS WITH LOW PROSTATE SPECIFIC ANTIGEN.
AB  - OBJECTIVE: To evaluate pituitary function in men with a low screening PSA of
      <=0.1 ng/ml, and test the hypothesis that low PSA is associated with hypogonadism
      alone or other hormone deficiency. METHODS: This is a case-controlled study
      evaluating the rates of hypogonadism and low IGF-1 in a cohort of men, with low
      or normal screening PSA level. Sixty-four men >40 years old without known
      prostate disease were divided into low PSA group (PSA <=0.1 ng/ml) and normal PSA
      group (PSA 1-4 ng/ml). Hormonal evaluation included total testosterone,
      prolactin, LH, FSH, IGF-1, GH, TSH, FT4, AM cortisol, and ACTH. The difference
      between each patient's observed IGF-1 and the IGF-1 age-specific lower limit was
      calculated. The odds ratios (OR) for having hypogonadism and associated 95%
      confidence intervals were calculated using the Cochran-Mantel-Haenszel test.
      RESULTS: The rate of hypogonadism was significantly higher in the low PSA group
      (N=44) compared with the normal PSA control group (N=20) (45.5% vs. 15.0%, OR =
      4.7, 95% CI for OR = 1.2 to 18.4, p = 0.027). The total testosterone in the low
      PSA group was significantly lower compared with control group (181.7 vs. 263.7
      ng/dl, p = 0.008). IGF-1 values were below their lower bound in 18.6 % of
      subjects in the low PSA group, compared with 0% in the control group. CONCLUSION:
      Men with low PSA have significantly higher rates of hypogonadism and low IGF-1
      compared with those with normal PSA. In such men, we recommend hormonal
      evaluation to exclude associated pituitary dysfunction. ABBREVIATIONS:
      PSA=Prostate specific antigen; LH=luteinizing hormone; FSH=follicle stimulating
      hormone; GH=growth hormone; IGF-1=Insulin like growth factor 1;
      ACTH=adrenocorticotropic hormone; TSH= thyrotropin releasing hormone; FT4= free
      thyroxine.

PMID- 30289305
TI  - ASSOCIATIONS OF SERUM IONIZED CALCIUM, PHOSPHATE, AND PTH LEVELS WITH TECHNETIUM
      99 SESTAMIBI PARATHYROID SPECT/CT SCAN IN PRIMARY HYPERPARATHYROIDISM.
AB  - OBJECTIVE: To evaluate the relationship between various biochemical parameters in
      patients with PHPT with positive and negative technetium-99 sestamibi parathyroid
      scans SPECT/CT (Tc scan). METHOD: Retrospective analysis. Development of a
      logistic probability model. There were 218 patients with PHPT evaluated. Main
      outcome measures were serum total calcium, ionized calcium, intact PTH, albumin,
      alkaline phosphatase, phosphate, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D,
      24-hour urine calcium levels and parathyroid adenoma weight. RESULTS:
      Individually, using cut-off levels of 6.0 mg/dL for ionized calcium, 3.0 mg/dL
      for phosphate, and 90 pg/mL for intact PTH, we found that 91.3% (p=0.005) , 70.7%
      (p=0.004) and 87.90% (p=0.023) of the patients had a positive Tc scan with their
      corresponding strengths of associations in the parentheses. Similar significant
      association was sustained in multivariate setting for serum ionized calcium (p =
      0.015), phosphate (p=0.016) and intact PTH (p=0.028). A logistic probability
      model was designed to predict the probability of being positive for Tc scan given
      a set of covariates. CONCLUSION: There is a significant association between the
      levels of serum ionized calcium, phosphate, intact PTH, and the positivity of Tc
      scan. Further studies with larger patient populations are needed. ABBREVIATIONS:
      BMD = Bone mineral density; BMI = body mass index; CT = computed tomography; CV =
      coefficient variation; DXA = dual-energy x-ray absorptiometry; GE = General
      Electric; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; MRI =
      magnetic resonance imaging; MET-PET-CT = C-11 methionine-positron emission
      tomography-computed tomography scan; NIH = National Institutes of Health; PPV =
      positive predictive value; SPECT= single-photon emission computed tomography; Tc
      scan = technetium-99 sestamibi parathyroid scan.

PMID- 30289306
TI  - A CAUTIONARY TALE OF HYPOPHYSITIS - RECOGNISING THE "SINISTER RADIOLOGICAL
      PATTERN".

PMID- 30289307
TI  - RISK FACTORS FOR CENTRAL LYMPH NODE METASTASES IN PATIENTS WITH PAPILLARY THYROID
      MICROCARCINOMA.
AB  - OBJECTIVES: Papillary thyroid carcinoma with a maximum tumor diameter no more
      than 10 mm is defined as papillary thyroid microcarcinoma (PTMC). The proportion
      of newly diagnosed PTMC has increased significantly in recent years. Different
      guidelines have different comments about optimal management of PTMC, especially
      on prophylactic central lymph node (CLN) dissection. The aim of the present study
      is to analyze the risk factors for CLN metastases in patients with PTMC. METHODS:
      A total of 4389 patients underwent thyroid surgery at our center from January
      2017 to March 2018, and 2129 patients with PTMC were selected and assessed
      retrospectively. The relationship between CLN metastases and clinicopathologic
      features of PTMC were analyzed by both univariate and multivariate analyses.
      RESULTS: Of the 2129 patients with PTMC, CLN metastases were confirmed by
      pathology in 923 patients. Univariate and multivariate analyses found several
      independent factors associated with CLN metastases. They were male gender
      (OR=1.694, 95% CI 1.386 - 2.071; p<0.001), younger age (< 45 years) (OR=2.687,
      95% CI 2.196 - 3.288; p<0.001), larger tumor size (> 5 mm) (OR=2.168, 95% CI
      1.782 - 2.636; p<0.001), positive CLN metastases via ultrasound (OR=4.939, 95% CI
      3.534 - 6.902; p<0.001), and multifocality (OR=1.424, 95% CI 1.176 - 1.724;
      p<0.001). CONCLUSION: CLN metastases are common in PTMC patients. Male gender,
      younger age (< 45 years), larger tumor size (> 5 mm), positive CLN metastases via
      ultrasound, and multifocality are independent factors for CLN metastases. Our
      data should be considered in the decision process relating to performing CLN
      dissection. ABBREVIATIONS: PTC = papillary thyroid carcinoma; PTMC = papillary
      thyroid microcarcinoma; CLN = central lymph node; BMI = body mass index.

PMID- 30289308
TI  - GOALS FOR MEDICAL TREATMENT IN OBESITY AND PREDIABETES: IMPROVING OUTCOMES FOR
      BOTH.
AB  - OBJECTIVE: The purpose of this review is to expose the surprising prevalence of
      diabetes-related complications in people with persistent prediabetes, and hence,
      to expand the paradigm of diabetes prevention to include the prevention of
      complications related to both hyperglycemia and obesity. METHODS: Published
      literature was reviewed. RESULTS: Approximately 84 million Americans have
      prediabetes, 85% of whom are overweight or obese. Although the incidence of
      diabetes-related complications is lower in people with prediabetes vs. type 2
      diabetes, the overall prevalence is virtually identical. Further, many people
      with prediabetes not only suffer from the complications of related to
      hyperglycemia, they also experience complications of obesity. Treating obesity as
      a disease has the potential to prevent complications of both hyperglycemia and
      obesity. Emerging data reveals the untapped potential for clinicians to enhance
      the effectiveness of anti-obesity medications through a mindful health care
      delivery style. This involves an understanding and ethical utilization of the
      placebo effect in conjunction with active medical therapy. This approach is not
      intended to mislead patients, but rather to activate neurocircuitry that
      synergizes with the central action of the approved anti-obesity medications to
      potentiate weight loss. CONCLUSIONS: Mindful administration of anti-obesity
      medications has the potential for widespread health benefits in people with
      obesity and prediabetes. ABBREVIATIONS: ADA = American Diabetes Association; AACE
      = American Association of Clinical Endocrinologists; DPP = Diabetes Prevention
      Program; DPPOS = Diabetes Prevention Program Outcomes Study; MVD = Microvascular
      disease; CVD = Cardiovascular disease; NDPP = National Diabetes Prevention
      Program; CDC = Centers for Disease Control; eGFR = Estimated glomerular
      filtration rate; TZD = Thiazolidinedione; SGLT2 Sodium-glucose-like cotransporter
      2.

PMID- 30289309
TI  - IT'S TIME TO STOP PRESCRIBING ERGOCALCIFEROL.

PMID- 30289310
TI  - REDUCED IMPACT OF DIABETES CLINIC REFERRAL ON HIGH FREQUENCY EMERGENCY DEPARTMENT
      USERS.
AB  - OBJECTIVE: The patterns of emergency department (ED) visits in patients with
      diabetes are not well understood. The Emergency Department Diabetes Rapid
      referral Program (EDRP) allows direct booking of ED patients presenting with
      urgent diabetes needs into a diabetes specialty clinic within 1 day of ED
      discharge. The objective of this secondary analysis was to examine
      characteristics of patients with diabetes who have frequent ED visits and
      determine reasons for revisits. METHODS: A single-center analysis was conducted
      comparing patients referred to the EDRP (n = 420) to historical unexposed
      controls (n = 791). The primary outcome was the proportion of patients in each
      frequency group of ED revisits (none, 1 to 3 [infrequent], 4 to 10 [frequent], or
      >10 [superfrequent]) in the year after the ED index visit. Secondary outcomes
      were hospitalization rates and International Classification of Diseases-Ninth
      Revision (ICD-9) diagnoses at ED revisits. RESULTS: Superfrequent users,
      responsible for >20% of total ED visits, made up small but not significantly
      different proportions of EDRP and control populations, 3.6% and 5.2%,
      respectively. Superfrequent groups had lower hospital admission rates at ED
      revisits compared to frequent groups. Mental health disorders (including
      substance abuse) were the primary, secondary, or tertiary ICD-9 codes in 30.6%
      (95% confidence interval [CI], 27.7% to 33.5%) and 6.6% (95% CI, 5.1% to 8.2%) in
      the superfrequent and infrequent groups, respectively. CONCLUSION: Direct access
      to diabetes specialty care from the ED is effective in reducing ED recidivism but
      not amongst a small subgroup of superfrequent ED users. This group was more
      likely to have mental health disorders recorded at ED revisits, suggesting that
      more comprehensive approaches are needed for this population. ABBREVIATIONS: EDRP
      = Emergency Department Diabetes Rapid-referral Program; ED = emergency
      department; HbA1c = hemoglobin A1c; ICD-9 = International Classification of
      Diseases-Ninth Revision.

PMID- 30289311
TI  - HYPOPHOSPHATASIA: CLINICAL ASSESSMENT AND MANAGEMENT IN THE ADULT PATIENT. A
      NARRATIVE REVIEW.
AB  - OBJECTIVE: To review literature and present a schematic approach to
      Hypophosphatasia (HPP) evaluation and management applicable to practicing
      physicians to ease its recognition and diagnosis. METHODS: Studies were obtained
      from online databases PubMed and MEDLINE using keyword Hypophosphatasia. RESULTS:
      HPP is a rare disease characterized by low serum alkaline phosphatase, along with
      diverse musculoskeletal symptoms, that mimic different disorders. To date, the
      prevalence of HPP and its impact on adults has been unrecognized. There is lack
      of evidence of larger and long term studies examining the adult type of this
      condition. CONCLUSION: It is essential to increase awareness on the complexity of
      the pathophysiology and clinical features of Hypophosphatasia. HPP causes
      debilitating physical conditions which severely affects quality of life. A better
      comprehension of adult forms of HPP is essential to reduce a delay in diagnosis,
      as well as suitable management. ABBREVIATIONS ALP = Alkaline phosphatase, CPPD =
      calcium pyrophosphate dehydrate, EDTA = ethylene diamine tetra acetic acid, HPP =
      Hypophosphatasia, HA = Hydroxyapatite, PLP = Pyridoxal-5-phosphate, Pi =
      Inorganic phosphate, PL= pyridoxal, PEA= phosphor ethanol amine, PTH= parathyroid
      hormone, OI= Osteogenesis Imperfecta, TNSALP/TNAP= Tissue Nonspecific Alkaline
      Phosphatase.

PMID- 30289312
TI  - GUT AND BONE CONNECTION: CELIAC DISEASE PRESENTED AS HYPERTROPHIC
      OSTEOARTHROPATHY.

PMID- 30289313
TI  - CALCIUM CREATININE CLEARANCE RATIO IS NOT HELPFUL IN DIFFERENTIATING PRIMARY
      HYPERPARATHYROIDISM FROM FAMILIAL HERPERCALCEMIC HYPOCALCIURIA: A STUDY OF 1000
      PATIENTS.
AB  - OBJECTIVE: With increasing recognition of more subtle presentations of primary
      hyperparathyroidism (pHPT), laboratory values are frequently seen in a range that
      would be expected for patients who have familial hypercalcemic hypocalciuria
      (FHH). Calcium creatinine clearance ratio (CCCR) has been advocated as a
      diagnostic tool to differentiate between these two disorders. However, it is
      limited by an indeterminate range (0.01-0.02). The aim of this study is to assess
      the relevance of CCCR in a modern series of patients with surgically managed
      pHPT. METHODS: We performed a retrospective cohort study of 1000 patients who
      underwent parathyroid surgery for pHPT over eleven years. CCCR was evaluated by
      degree of biochemical derangement, single versus multiple gland disease and
      interfering medications. RESULTS: Patient demographics and resected
      histopathology were typical for a current series of patients with pHPT. In
      retrospect, none of the patients were suspected to have FHH post operatively.
      CCCR was less than 0.01 for 19.0%, between 0.01-0.02 for 43.7% and greater than
      0.02 in 37.3%. Distribution of CCCR for patients free from interfering
      medications and different histological subtypes were the same. One third of the
      cohort had mild calcium elevations, more typical for FHH. Of these, almost two
      thirds had a CCCR in a range suspect for FHH (<0.02). CONCLUSION: To our
      knowledge this is the largest series to evaluate the validity of CCCR for
      patients with surgically confirmed pPHT. The utility of CCCR in screening for FHH
      is limited, as 63% of modern patients with confirmed pHPT have low values.

PMID- 30289314
TI  - MAKING A DIFFERENCE IN ADRENAL FATIGUE.

PMID- 30289315
TI  - REGULATION OF FREE FATTY ACIDS BY SITAGLIPTIN MONOTHERAPY IN DRUG NAIVE SUBJECTS
      WITH TYPE 2 DIABETES.
AB  - OBJECTIVES: The aim of this study is to investigate the effects of sitagliptin on
      the regulation of FFA and other metabolic parameters in drug-naive subjects with
      T2DM. SUBJECTS AND METHODS: This is a prospective, non-randomized, observational
      study. Drug naive subjects with T2DM received 25-50 mg/day sitagliptin
      monotherapy (n=64). At 3 months, FFA and other metabolic parameters were compared
      with those at baseline. FFA was measured by colorimetry with enzymatic reactions.
      As a comparator, 12.5-25mg/day alogliptin monotherapy was given to drug naive
      subjects with T2DM (n=55). RESULTS: Significant reductions in FFA (-13.2 %,
      p<0.01) levels were observed with sitagliptin, however, not with alogliptin. Both
      drugs showed similar glycemic efficacies. Significant correlations were observed
      between the changes (Delta) of FFA and DeltaHbA1c, DeltaT-C, Deltanon-HDL-C or
      DeltaLDL-C, and significant negative correlations were seen between DeltaFFA and
      DeltaHOMA-B, DeltaCPR-index or DeltaBMI in the sitagliptin group. The subjects in
      the sitagliptin group were further divided into two subgroups (n=32 each)
      according to the changes of FFA (group B [above the median] DeltaFFA =23.1 %,
      p<0.0005; group A [below the median] DeltaFFA=-37.3 %, p<0.00001). At baseline,
      FFA levels were significantly higher in group A versus group B (p<0.001). Higher
      degrees of reductions of FBG (-14.6% vs. -9.3%, p<0.05) or HbA1c (-20.6% vs. 
      16.9%, p<0.05), and increases of HOMA-B (52.7% vs. 38.3%, p<0.03) or CPR-index
      (37.5% vs. 18.8%, p<0.02) were observed in group A versus group B. Significant
      reductions of T-C (-5.8%, p<0.002), non-HDL-C (-7.8%, p<0.001) or LDL-C (-6.3%,
      p<0.02), and significant increases of C-peptide (11.3%, p<0.05) were seen only in
      group A. CONCLUSIONS: Sitagliptin could down-regulate high FFA levels. Subjects
      with reductions of FFA levels had better glycemic efficacies and higher degrees
      of enhancement of beta-cell function than others. Reductions of atherogenic
      cholesterols were seen in these populations. ABBREVIATIONS: FFA = free fatty
      acid; T2DM = type 2 diabetes; FBG = fasting blood glucose; HOMA-R = homeostasis
      model assessment-R; HOMA-B = homeostasis model assessment-B; T-C = total
      cholesterol; TG = triglyceride; HDL-C = high density lipoprotein cholesterol; non
      HDL-C = non-HDL-cholesterol; LDL-C = low density lipoprotein cholesterol.

PMID- 30289316
TI  - Trunk control and gross motor outcomes after body weight supported treadmill
      training in young children with severe cerebral palsy: a non-experimental case
      series.
AB  - OBJECTIVE: To explore the impact of a body weight supported treadmill training
      (BWSTT) intervention on postural control and gross motor function in three young
      children with cerebral palsy (CP) classified as Gross Motor Function
      Classification System (GMFCS) levels IV or V. METHOD: Children (N = 3) between
      the ages of 2-3 years who were diagnosed with CP classified as GMFCS levels IV
      and V participated in BWSTT three times per week. The Segmental Assessment of
      Trunk Control (SATCo) and the gross motor function measure (GMFM-66) were
      assessed before and after the 6-week intervention. RESULTS: Final testing
      revealed that all participants improved on the SATCo and GMFM. CONCLUSION: BWSTT
      is a viable intervention that may improve trunk control and gross motor outcomes
      in young children with severe CP. Further research is needed to explore the
      impact of BWSTT for young children classified as GMFCS levels IV and V.

PMID- 30289317
TI  - Cervical cancer screening among immigrant women in Norway- The healthcare
      providers' perspectives.
AB  - OBJECTIVE: To explore health care providers' (HCPs) experiences regarding
      cervical cancer screening (CCS) among immigrant women, their strategies to
      facilitate these consultations and their need for further information. DESIGN:
      Exploratory qualitative design. SETTING: HCPs who perform CCS: general
      practitioners, midwives and private gynaecologists, working in Oslo, Norway.
      SUBJECTS: We interviewed 26 general practitioners, 3 midwives and 3
      gynaecologists. METHOD: Both focus groups and personal in depth semi structured
      interviews. Interview transcripts were analysed using a thematic analysis
      approach. RESULTS: Some of the HCPs' experiences related to CCS were common for
      all women regardless of their immigrant background, such as the understanding of
      routines and responsibilities for prevention. Aspects specific for immigrant
      women were mainly related to organization, language, health literacy levels,
      culture and gender. Several strategies targeting organizational (longer
      consultations), language (using interpreters), health literacy (using anatomy
      models to explain) and culture (dealing with the expression of pain) were
      reported. Most HCPs had not previously reflected upon specific challenges linked
      to CCS among immigrant women, thus the interviews were an eye-opener to some
      extent. HCPs acknowledged that they need more knowledge on immigrant women's'
      reproductive health. CONCLUSION: HCPs' biases, stereotypes and assumptions could
      be a key provider-level barrier to low uptake of CCS test among immigrants if
      they remained unexplored and unchallenged. HCPs need more information on
      reproductive health of immigrant women in addition to cultural awareness. Key
      Points The participation rate of immigrant women to cervical cancer screening in
      Norway is low, compared to non-immigrants. This might be partly attributed to
      health care system and provider, and not only due to the women's preferences. Our
      focus groups and interviews among health care providers show, that in addition to
      cultural competence and awareness, they need knowledge on reproductive health of
      immigrants. We recommend an intervention targeting health care providers to close
      the gap in cervical cancer screening.

PMID- 30289318
TI  - Everyday memory difficulties in children and adolescents with Fetal Alcohol
      Spectrum Disorder.
AB  - PURPOSE: To investigate whether significant differences exist in everyday memory
      between youth with Fetal Alcohol Spectrum (FASD) compared with a nonexposed (NE)
      control group, while controlling for socioeconomic status and other
      comorbidities. METHODS: Caregiver ratings using the Everyday Memory Questionnaire
      were obtained for 105 youth (9-17 years of age). Scores were compared between
      youth with a FASD diagnosis (N = 41; 56% male) and the NE group (N = 64; 53%
      male) using multivariate analysis of variance. RESULTS: Significantly poorer
      scores were found across all domains of everyday memory in youth with FASD
      (p<0.01 for all comparisons). Findings maintained significance after controlling
      for group differences in socioeconomic status, presence of learning, and
      attention disorders, as well as exposure to other teratogens. CONCLUSIONS: This
      study provides important insights regarding the memory issues that underlie daily
      functional challenges faced by youth with FASD and the need for future
      intervention research.

PMID- 30289319
TI  - Novel causative variants in patients with achromatopsia.
AB  - PURPOSE: To report five novel genetic variants in seven unrelated consanguineous
      families with achromatopsia (ACHM). METHODS: Patients were examined with
      multimodal retinal imaging and full-field electroretinography (ffERG). Genetic
      testing was conducted using next-generation sequencing (NGS). RESULTS: Three
      novel homozygous variants were detected in CNGA3: a missense c.967G > C
      (p.Ala323Pro) variant was detected in exon 8 (one patient), a splice site variant
      c.101 + 1G > A in intron 2 (three patients), and a splice site variant c.395 + 1G
      > T in intron 4(one patient). Another two novel variants were found in PDE6C: a
      homozygous missense variant c.1899C > A (p.His633Gln) in exon 15 (one patient)
      and a homozygous splice site variant c.1072-1G > C in intron 7 (one patient).
      Mutation segregation assessment was possible in 3 of the 7 families. All patients
      had nonrecordable ffERG 30-Hz flicker responses, reduced single-flash cone
      responses but preserved rod responses. Patients presented with variable degrees
      of foveal outer retinal layer loss and variable patterns of foveal
      hyperautofluorescence. CONCLUSIONS: These novel variants expand the genotypes
      associated with ACHM and may help in future therapy development for ACHM.

PMID- 30289320
TI  - First four years of operation of a municipal acute bed unit in rural Norway.
AB  - OBJECTIVE: To evaluate the use of a small municipality acute bed unit (MAU) in
      rural Norway resulting from the Coordination reform regarding occupancy-rate,
      patient characteristics and healthcare provided during the first four years of
      operation. Further, to investigate whether implementation of the new municipal
      service avoided acute hospital admissions. DESIGN: Observational study. SETTING:
      A two-bed municipal acute bed unit. SUBJECTS: All patients admitted to the unit
      between 2013 and 2016. MAIN OUTCOME MEASURES: Demographics, comorbidity, main
      diagnoses and level of municipal care on admission and discharge, diagnostic and
      therapeutic initiatives, MAU occupancy rate, and acute hospital admission rate.
      RESULTS: Altogether, 389 admissions occurred, 215 first-time admissions and 174
      readmissions. The mean MAU bed occupancy rate doubled from of 0.26 in 2013 to
      0.50 in 2016, while acute hospital admission rates declined. The patients (median
      age 84.0 years, 48.9% women at first time admission) were most commonly admitted
      for infections (28.0%), observation (22.1%) or musculoskeletal symptoms (16.2%).
      Some 52.7% of the patients admitted from home were discharged to a higher care
      level; musculoskeletal problems as admission diagnosis predicted this (RR =1.43,
      95% CI 1.20-1.71, adjusted for age and sex). CONCLUSION: Admission rates to MAU
      increased during the first years of operation. In the same period, there was a
      reduction in acute hospital admissions. Patient selection was largely in
      accordance with national and local criteria, including observational stays. Half
      the patients admitted from home were discharged to nursing home, suggesting that
      the unit was used as pathway to a higher municipal care level. Key Points
      Evaluation of the first four years of operation of a municipality acute bed unit
      (MAU) in rural Norway revealed: * Admission rates to MAU increased, timely
      coinciding with decreased acute admission rates to hospital medical wards. * Most
      patients were old and had complex health problems. * Only half the patients were
      discharged back home; musculoskeletal symptoms were associated with discharge to
      a higher care level.

PMID- 30289321
TI  - An evaluation of the additive effects of lag schedules of reinforcement.
AB  - Lag schedules of reinforcement represent an increasingly researched strategy for
      addressing restricted and repetitive social communication of individuals with
      autism spectrum disorder (ASD). Although the body of literature suggests that lag
      schedules of reinforcement are generally effective for this purpose, studies have
      varied in their utilization of verbal rules describing the contingency.
      Furthermore, research has yet to evaluate generalized effects of lag schedules of
      reinforcement to social communication with peers. This study evaluated the
      implementation of a social skills curriculum, modified to incorporate lag
      schedules of reinforcement, on novel responding of participants with ASD.
      Participants attended training twice per week, with probes of novel responding
      collected with both researchers and non-participating peers. Results indicate
      that social skills training that incorporated lag schedules of reinforcement
      generally resulted in larger increases in novel responding than social skills
      training alone. Furthermore, effects of training generalized to novel responding
      to non-participant peers.

PMID- 30289322
TI  - Association analysis of genetic polymorphisms and expression levels of selected
      genes involved in extracellular matrix turnover and angiogenesis with the risk of
      age-related macular degeneration.
AB  - BACKGROUND: Age-related macular degeneration is a progressive eye disease
      affecting the macula and causing acute visual loss particularly in elder people.
      The aim of the study was an attempt to discern an influence of expression levels
      and functional genetic polymorphisms of selected genes related to the
      extracellular matrix turnover or neovascularization on age-related macular
      degeneration occurrence and progression. METHODS: We conducted a case-control
      study of 200 polish patients with recognized age-related macular degeneration
      (dry and wet) and compared the results with those obtained from matched 100
      healthy control subjects. TaqMan Genotyping Assays were employed to examine the
      following single nucleotide polymorphisms: matrix metalloproteinase (MMP)-2 
      735C/T, MMP-7 -181A/G, MMP-9 -1702T/A, and -1562C/T; tissue inhibitors of
      metalloproteinase (TIMP)-2 -418G/C; vascular endothelial growth factor (VEGF)
      +405 G/C and +936 C/T, VEGFR-2 +1719 T/A and -271 G/A. Real-time polymerase chain
      reaction was assessed to determine the mRNA quantity. Serum levels of proteins
      were measured using enzyme-linked immunosorbent assay. RESULTS: The single
      nucleotide polymorphism genotyping showed that TT genotype for MMP-9 -1702T/A and
      CC genotype for VEGF +936C/T increase markedly the risk of age-related macular
      degeneration but do not influence on its progression. Additionally, the possible
      protective effect of CC genetic variant in MMP-9 -1562C/T polymorphism against
      progression of age-related macular degeneration was observed. We also found
      significant differences in systemic expression levels of MMP-2, -7, -9, TIMP-2,
      vascular endothelial growth factor, VEGFR-2, and pigment epithelium-derived
      factor between studied group. The research demonstrated evident differences in
      serum levels of MMP-2, -7, -9, TIMP-2, vascular endothelial growth factor, and
      pigment epithelium-derived factor between wet and dry age-related macular
      degeneration patients. CONCLUSIONS: We can conclude that disturbances in
      angiogenic homeostasis and processes of extracellular matrix turnover occurring
      in age-related macular degeneration-affected ocular tissues may be reflected in
      changes in systemic expression levels of the investigated genes.

PMID- 30289324
TI  - Management of Polyarthritis Affecting Sea Turtles at Kelonia, the Reunion Island
      Sea Turtle Observatory (2013-17).
AB  - All sea turtle species are listed on the Red List of the International Union for
      the Conservation of Nature due to multiple threats. Among these, disease is a
      frequent cause of stranded sea turtles encountered in rehabilitation centers.
      Since 2013, we found joint swelling in 13 sea turtles belonging to all four sea
      turtle species submitted to the Kelonia Sea Turtle Observatory of Reunion Island,
      France. Affected sea turtles presented with lameness, anorexia, and lethargy.
      Polyarthritis was radiographically confirmed and lesions were characterized by
      progressive osteolysis of bones surrounding joints. Anterior flippers were
      affected in all cases and posterior flippers were also involved in some cases. We
      isolated several bacterial agents from blood and synovial fluid. We attempted a
      collective treatment with injectable florfenicol, based on sensitivity results,
      which was continued for 4 wk and then as needed based on radiographic evolution
      of the lesions. Radiographic stabilization of the lesions occurred in nine of 13
      cases. We reviewed environmental conditions and optimized them to minimize stress
      that could predispose these rehabilitated sea turtles to opportunistic
      infections. Handling techniques used to move sea turtles were also improved.
      While we can make no conclusion regarding the cause of polyarthritis in this
      population of sea turtles, we successfully managed this poorly described problem
      in a rehabilitation setting.

PMID- 30289325
TI  - Top Ten Tips Palliative Care Clinicians Should Know About Caring for Children.
AB  - Given the limited number of pediatric-specific palliative care programs,
      palliative care providers of all disciplines may be called on to care for
      infants, children, and adolescents with serious illness. This article provides a
      review of the unique components of pediatric palliative care, including key roles
      within an interdisciplinary team, pediatric developmental considerations, use of
      medical technology and complexities of symptom management in children with
      serious illness, hospice utilization, as well as pointers for discussions with
      families regarding a patient's quality of life and goals of care.

PMID- 30289326
TI  - Serologic Survey of Selected Viral Pathogens in Free-Ranging Eurasian Brown Bears
      ( Ursus arctos arctos) from Slovakia.
AB  - We tested sera of 24 free-ranging European brown bears ( Ursus arctos) from six
      regions of Slovakia for antibodies to 10 viral agents. We tested sera by an
      indirect fluorescence antibody test for antibodies to canine distemper virus
      (CDV), canine coronavirus (CCV), canine parvovirus type 2 (CPV-2), canine
      adenovirus, canine parainfluenza virus type 2 (CPIV-2), and canine herpesvirus
      type 1 (CHV-1). We used an enzyme-linked immunosorbent assay for detection of
      antibodies to hepatitis E virus, bluetongue virus, West Nile virus (WNV), and
      Aujeszky's disease virus (ADV). We detected antibodies to CDV, CHV-1, CPV-2, CPIV
      2, CCV, WNV, and ADV in seven (29%), three (12%), two (8%), two (8%), one (4%),
      one (4%), and one (4%) bear, respectively. Evidence of exposure of free-ranging
      European brown bears to CCV and ADV has not been reported.

PMID- 30289327
TI  - Long-term quality of life after comprehensive surgical staging of high-risk
      endometrial cancer - results from the RASHEC trial.
AB  - PURPOSE: The health-related quality of life (HRQoL) outcomes after comprehensive
      surgical staging including infrarenal paraaortic lymphadenectomy in women with
      high-risk endometrial cancer (EC) are unknown. Our aim was to investigate the
      long-term HRQoL between robot-assisted laparoscopic surgery (RALS) and laparotomy
      (LT). PATIENTS AND METHODS: A total of 120 women with high-risk stage I-II EC
      were randomised to RALS or LT for hysterectomy, bilateral salpingoophorectomy,
      pelvic and infrarenal paraaortic lymphadenectomy in the previously reported Robot
      Assisted Surgery for High-Risk Endometrial Cancer trial. The HRQoL was measured
      with the European Organisation for Research and Treatment of Cancer Quality of
      Life Questionnaire Core 30 (EORTC-QLQ-30) and its supplementary questionnaire
      module for endometrial cancer (QLQ-EN24) questionnaire. Women were assessed
      before and 12 months after surgery. In addition, the EuroQol Eq5D non-disease
      specific questionnaire was used for descriptive analysis. RESULTS: There was no
      difference in the functional scales (including global health status) in the
      intention to treat analysis, though LT conferred a small clinically important
      difference (CID) over RALS in 'cognitive functioning' albeit not statistically
      significant -6 (95% CI-14 to 0, p = .06). LT conferred a significantly better
      outcome for the 'nausea and vomiting' item though it did not reach a CID, 4 (95%
      CI 1 to 7, p = .01). In the EORTC-QLQ/QLQ-EN24, no significant differences were
      observed. Eq5D-3L questionnaire demonstrated a higher proportion of women
      reporting any extent of mobility impairment 12 months after surgery in the LT arm
      (p = .03). CONCLUSION: Overall, laparotomy and robot-assisted surgery conferred
      similar HRQoL 12 months after comprehensive staging for high-risk EC.

PMID- 30289328
TI  - Hematologic and Serum Chemistry Values of Endangered San Joaquin Kit Foxes (
      Vulpes macrotis mutica) with Sarcoptic Mange.
AB  - A fatal outbreak of sarcoptic mange caused by Sarcoptes scabiei in San Joaquin
      kit foxes ( Vulpes macrotis mutica) in Bakersfield, California, USA is causing
      the once-stable population to decline. Given the fatality of the disease in this
      already-endangered species experiencing continued population declines, city-wide
      interventions are underway. To optimize medical management of mange-infested kit
      foxes, we documented serum biochemistry and hematology values for 11 kit foxes
      with mange collected from January-May 2015 and compared them to historical data
      from 18 healthy Bakersfield kit foxes. Results from kit foxes with mange were
      consistent with chronic illness and inflammation, protein loss, hypoglycemia, and
      dehydration. These findings contribute to our understanding of this debilitating,
      multisystemic disease that can progress to death in individuals without
      intervention and will aid in the treatment and care of rehabilitated individuals.

PMID- 30289329
TI  - Topical Cyclosporine Pretreatment of Ocular Surface in Allogeneic Hematopoietic
      Stem Cell Transplant Recipients.
AB  - PURPOSE: Dry eye disease (DED) of ocular graft-versus-host disease (GVHD) is a
      common complication after allogeneic hematopoietic stem cell transplantation
      (HSCT). Ongoing inflammation and irreversible fibrotic changes of the ocular
      surface and adnexa are obstacles for effective treatment of ocular GVHD. We
      hypothesized that topical cyclosporine A (CsA) pretreatment might be effective in
      preventing ocular GVHD. METHODS: In this prospective, randomized, comparative
      study, patients were randomly assigned to the topical CsA treatment (4 times
      daily in both eyes for a month before allogeneic HSCT and continued use of eye
      drops after transplantation) or control (no treatment) groups. Participants
      underwent thorough ophthalmic examination-including Ocular Surface Disease Index
      questionnaire survey, Schirmer test, tear break-up time (TBUT) evaluation, and
      corneal fluorescein staining-before and 1, 2, and 3 months after allogeneic HSCT.
      RESULTS: Fifty-eight participants completed the study. Among patients with
      baseline Schirmer values <10 mm and TBUT <5 s before allogenic HSCT, those in the
      topical CsA treatment group exhibited significantly better corresponding values
      after transplantation than patients in the control group. CONCLUSIONS: Topical
      CsA pretreatment might be beneficial in the early stage of DED and might prevent
      further inflammation and consequent irreversible fibrosis, especially in patients
      with preexisting DED components.

PMID- 30289330
TI  - Changes in Detected Anticoagulant Rodenticide Exposure in Barn Owls ( Tyto alba)
      in Kentucky, USA, in 2012-16.
AB  - Anticoagulant rodenticides (ARs) are widely used across North America to control
      rodent infestations but may cause direct mortality or nonlethal effects when
      secondarily consumed by raptors. Barn Owls ( Tyto alba) are at high risk for
      secondary consumption because they specialize in rodent prey and often live in
      human-made structures. We investigated the exposure of Barn Owls in Kentucky, US,
      to ARs and to dicoumarol, an anticoagulant compound naturally found in certain
      moldy forages. We tested the liver tissue of 48 Barn Owl carcasses collected
      during 2012-16. We confirmed exposure to one or more ARs in 33% of the birds
      examined and detected dicoumarol in 13% of the samples. Rodenticides detected
      included brodifacoum, coumachlor, and bromadiolone. The prevalence of detected
      exposure to brodifacoum for after-hatch-year birds (65%) was significantly (
      P=0.012) higher than hatch-year birds (22%). Brodifacoum was the most commonly
      detected AR, found in 88% of AR-positive birds. The pesticide registration for
      this chemical in the US was canceled in 2015 for general consumer products, which
      likely resulted in a decreasing rate of detected exposure to brodifacoum during
      our study. We present these results as an example of secondary exposure rates
      during a period when a pesticide has been restricted and then removed from the
      consumer market.

PMID- 30289331
TI  - Survey of Arctic Alaskan Wildlife For Influenza A Antibodies: Limited Evidence
      For Exposure of Mammals.
AB  - Influenza A viruses (IAVs) are maintained in wild waterbirds and have the
      potential to infect a broad range of species, including wild mammals. The Arctic
      Coastal Plain of Alaska supports a diverse suite of species, including waterfowl
      that are common hosts of IAVs. Mammals co-occur with geese and other migratory
      waterbirds during the summer breeding season, providing a plausible mechanism for
      interclass transmission of IAVs. To estimate IAV seroprevalence and identify the
      subtypes to which geese, loons, Arctic foxes ( Vulpes lagopus), caribou (
      Rangifer tarandus), and polar bears ( Ursus maritimus) are potentially exposed,
      we used a blocking enzyme-linked immunosorbent assay (bELISA) and a
      hemagglutination inhibition (HI) assay to screen for antibodies to IAVs in
      samples collected during spring and summer of 2012-16. Apparent IAV
      seroprevalence using the bELISA was 50.7% in geese (range by species: 46.1
      52.8%), 9.2% in loons, (range by species: 3.4-20.0%), and 0.4% in Arctic foxes.
      We found no evidence for exposure to IAVs in polar bears or caribou by either
      assay. Among geese, we estimated detection probability from replicate bELISA
      analyses to be 0.92 and also found good concordance (>85%) between results from
      bELISA and HI assays, which identified antibodies reactive to H1, H6, and H9
      subtype IAVs. In contrast, the HI assay detected antibodies in only one of seven
      loon samples that were positive by bELISA; that sample had low titers to both H4
      and H5 IAV subtypes. Our results provide evidence that a relatively high
      proportion of waterbirds breeding on the Arctic Coastal Plain are exposed to
      IAVs, although it is unknown whether such exposure occurs locally or on staging
      or wintering grounds. In contrast, seroprevalence of IAVs in concomitant mammals
      is apparently low.

PMID- 30289333
TI  - 7th International Society for Physical Activity and Health Congress.

PMID- 30289332
TI  - Treatment Recommendations for Urological Symptoms in Cancer Patients: Clinical
      Guidelines from the Japanese Society for Palliative Medicine.
AB  - BACKGROUND: Urological symptoms such as gross hematuria, lower and upper urinary
      tract symptoms, and bladder pain are common in and distressing for patients with
      advanced cancer. Although palliation of urological symptoms is important to
      improve the quality of life of cancer patients and their families and caregivers,
      clinical guidelines for managing urological symptoms in patients with cancer have
      not been published. METHODS: Following the formal guideline development process,
      the Japanese Society for Palliative Medicine (JSPM) developed comprehensive
      clinical guidelines for the management of urological symptoms in patients with
      cancer. RESULTS: This article summarizes the recommendations and their rationales
      and provides a short summary of the development process of the JSPM urological
      symptom management guidelines. We established five recommendations, all of which
      were based on the best available evidence and expert consensus. CONCLUSION: JSPM
      released the first edition of the "Clinical Guidelines for Urological Symptoms in
      Cancer Patients." Future clinical research and continuous guideline updates are
      required to improve the quality of managing urological symptoms in patients with
      cancer.

PMID- 30289334
TI  - Genetic Characterization of Canine Parvovirus 2 Detected in Wild Raccoon Dogs (
      Nyctereutes procyonoides) in the Republic of Korea.
AB  - Canine parvovirus (CPV) was detected in three of 136 samples from dead raccoon
      dogs ( Nyctereutes procyonoides) in the Republic of Korea (South Korea) during
      2016-17. By sequence and phylogenetic analysis of the complete VP2 gene, the
      strain belonged to CPV-2 and would be distinct from the previous reported CPV-2a
      and CPV-2b strains from Korean domestic dogs ( Canis lupus familiaris). The
      results indicated that the CPV strains from raccoon dogs and domestic dogs might
      be not circulated between wild and domestic carnivores in Korea.

PMID- 30289335
TI  - Activated kinase screening identifies the IKBKE oncogene as a positive regulator
      of autophagy.
AB  - : Macroautophagy/autophagy is one of the major responses to stress in eukaryotic
      cells and is implicated in several pathological conditions such as infections,
      neurodegenerative diseases and cancer. Interestingly, cancer cells take full
      advantage of autophagy both to support tumor growth in adverse microenvironments
      and to oppose damages induced by anti-neoplastic therapies. Importantly,
      different human oncogenes are able to modulate this survival mechanism to support
      the transformation process, ultimately leading to 'autophagy addiction'. Still,
      oncogenic signaling events, impinging on the control of autophagy, are poorly
      characterized, limiting our possibilities to take advantage of these mechanisms
      for therapeutic purposes. Here, we screened a library of activated kinases for
      their ability to stimulate autophagy. By this approach, we identified novel
      potential regulators of the autophagic process and, among them, the IKBKE
      oncogene. Specifically, we demonstrate that this oncoprotein is able to stimulate
      autophagy when overexpressed, an event frequently found in breast tumors, and
      that its activity is strictly required for breast cancer cells to support the
      autophagic process. Interestingly, different oncogenic pathways typically
      involved in breast cancer, namely ERBB2 and PI3K-AKT-MTOR, also rely on IKBKE to
      control this process. Ultimately, we show that IKBKE-dependent autophagy is
      necessary for breast cancer cell proliferation, suggesting an important
      supporting role for this oncogene and autophagy in these tumors. ABBREVIATIONS:
      AAK1: AP2 associated kinase 1; AMPK: 5'-prime-AMP-activated protein kinase; AKT1:
      AKT serine/threonine kinase 1; BAF: bafilomycin A1; CA: constitutively activated;
      CDK17: cyclin dependent kinase 17; CDK18: cyclin dependent kinase 18; CHUK:
      conserved helix-loop-helix ubiquitous kinase; EGF: epidermal growth factor;
      ERBB2: erb-b2 receptor tyrosine kinase 2; FGF: fibroblast growth factor; FM: full
      medium; GALK2: galactokinase 2; IKBKB: inhibitor of nuclear factor kappa B kinase
      subunit beta; IKBKE: inhibitor of nuclear factor kappa B kinase subunit epsilon;
      IKK: IkappaB kinase complex; KD: kinase dead; MAP1LC3B/LC3B: microtubule
      associated protein 1 light chain 3 beta; MAPK1: mitogen-activated protein kinase
      1; MAPK15: mitogen-activated protein kinase 15; MTORC1: mammalian target of
      rapamycin kinase complex 1; myr: myristoylation/myristoylated; NFKBIA: NFKB
      inhibitor alpha; PDGF: platelet derived growth factor; PFKL: phosphofructokinase,
      liver type; PRKAA1: protein kinase AMP-activated catalytic subunit alpha 1;
      PRKCD: protein kinase C delta; SQSTM1: sequestosome 1; TBK1: TANK binding kinase
      1; TNBC: triple-negative breast cancer; TSC2: TSC complex subunit 2; WB: western
      blot; WT: wild-type.

PMID- 30289336
TI  - Protein kinase C Inhibitors selectively modulate dynamics of cell adhesion
      molecules and cell death in human colon cancer cells.
AB  - : During development of colon cancer, Protein Kinase Cs (PKCs) are involved in
      regulation of many genes controlling several cellular mechanisms. Here, we
      examined the changes in cell adhesion molecules and PKCs for colorectal cancer
      progression. We identified that PKCs affected expression of EpCAM, claudins,
      tetraspanins. Treatment with low concentrations of PKC inhibitors resulted in
      decreased cell viability. In addition, immunoblotting and qRT-PCR analysis showed
      that apoptosis was inhibited while autophagy was induced by PKC inhibition in
      colon cancer cells. Furthermore, we observed decreased levels of intracellular
      Reactive Oxygen Species (ROS), lipid peroxidation and protein carbonyl,
      confirming the ROS-induced apoptosis. Taken together, our results reveal that PKC
      signalling modulates not only cell adhesion dynamics but also cell death-related
      mechanisms. ABBREVIATIONS: PKC: Protein Kinase C; EpCAM: Epithelial cell adhesion
      molecule; FBS: fetal bovine serum; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide); CAM: cell adhesion molecule; ROS: reactive oxygen
      species.

PMID- 30289337
TI  - Metagenomic Next-Generation Sequencing Reveals Miamiensis avidus (Ciliophora:
      Scuticociliatida) In the 2017 Epizootic of Leopard Sharks ( Triakis semifasciata)
      In San Francisco Bay, California, USA.
AB  - During March to August of 2017, hundreds of leopard sharks ( Triakis
      semifasciata) stranded and died on the shores of San Francisco Bay, California,
      USA. Similar mass stranding events occurred in 1967 and 2011, but analysis of
      those epizootics was incomplete, and no etiology was confirmed. Our investigation
      of the 2017 epizootic revealed severe meningoencephalitis in stranded sharks,
      raising suspicion for infection. We pursued a strategy for unbiased pathogen
      detection using metagenomic next-generation sequencing followed by orthogonal
      validation and further screening. We showed that the ciliated protozoan pathogen,
      Miamiensis avidus, was present in the central nervous system of leopard ( n=12)
      and other shark species ( n=2) that stranded in San Francisco Bay but was absent
      in leopard sharks caught elsewhere. This ciliated protozoan has been implicated
      in devastating outbreaks in teleost marine fish but not in wild elasmobranchs.
      Our results highlight the benefits of adopting unbiased metagenomic sequencing in
      the study of wildlife health and disease.

PMID- 30289338
TI  - Isolation, Not Loneliness or Cynical Hostility, Predicts Cognitive Decline in
      Older Americans.
AB  - OBJECTIVE: To jointly examine isolation, loneliness, and cynical hostility as
      risk factors for cognitive decline in older adults. METHOD: Data came from the
      2006 to 2012 waves of the Health and Retirement Study (HRS), a longitudinal study
      of U.S. older adults (age ? 65 years, n = 6,654). Measures included frequency of
      contact with social network (objective isolation), the Hughes Loneliness Scale
      (loneliness), a modified version of the Cook-Medley Hostility Inventory (cynical
      hostility), and a modified version of the Telephone Interview for Cognitive
      Status (cognitive function). Multilevel modeling (random slope + intercept) was
      used to examine the association between these factors and trajectories of
      cognitive function. RESULTS AND DISCUSSION: After controlling for demographic
      characteristics, self-reported health, and functional limitations, loneliness
      (beta = -.34, 95% confidence interval [CI] = [-0.56, -0.11), and cynical
      hostility (beta = -.14, 95% CI = [-0.24, -0.04) correlated with lower cognitive
      function, but none predicted change in cognitive function. Objective social
      isolation was associated with lower cognitive function (beta = -.27, 95% CI = [
      0.41, -0.12]) and steeper decline in cognitive function (beta = -.09, 95% CI = [
      0.16, -0.01]).

PMID- 30289339
TI  - A Determinants of Health Conceptual Model for Fish and Wildlife Health.
AB  - Our objectives were to establish if the determinant of health model used in the
      fields of human population and public health could be adapted to wildlife health;
      if it was applicable to more than one species; and if it reflected how fish and
      wildlife managers conceptualized health in practice. A conceptual model was
      developed using a scoping review on fish and wildlife health and resilience
      coupled with a participatory process with experts on barren ground caribou (
      Rangifer tarandus groenlandicus) and sockeye salmon ( Oncorhynchus nerka) health.
      Both the literature and experts supported the concept of wildlife health as a
      cumulative effect involving multiple factors that extend beyond the disease and
      pathogen focus of many wildlife health studies and legislation. Seven themes were
      associated with fish and wildlife health: 1) the biologic endowment of the
      individual and population; 2) the animal's social environment; 3) the quality and
      abundance of the animal's needs for daily living; 4) the abiotic environment in
      which the animal lives; 6) sources of direct mortality; and 7) changing human
      expectations. These themes were shared between salmon and caribou and conformed
      to expert perceptions of health. Determinants of health used in human public
      health are used for planning, development of policy, and guiding of research. The
      model we produced may also have use as a wildlife health planning tool to help
      managers identify health protection priorities and to promote actions across the
      determinants of health.

PMID- 30289340
TI  - Density override in treatment planning to mitigate the dosimetric effect induced
      by gastrointestinal gas in esophageal cancer radiation therapy.
AB  - PURPOSE: To investigate the dosimetric effect of variable gas volume in
      esophageal cancer radiation therapy (RT) and whether a density override (DO) in
      treatment planning can effectively mitigate this dosimetric effect. MATERIAL AND
      METHODS: Nine patients with gastrointestinal gas pockets in the planning computed
      tomography (pCT) were retrospectively included. Per patient, the intensity
      modulated RT (IMRT) and volumetric-modulated arc therapy (VMAT) plans associated
      with no DO, DO = 0.5, and DO = 1 in the gas pockets were made. Initial and follow
      up gas volumes were assessed from the pCTs and cone-beam CTs (CBCTs),
      respectively. Fractional CTs were created based on the pCT and CBCTs to calculate
      the fractional doses using all six plans. We then investigated for all six plans
      the correlation between the gas volume difference (relative to initial gas
      volume) and the dose difference (relative to planned dose). We also calculated
      and compared the accumulated dose by summing the fractional doses using two
      strategies: single-plan strategy (i.e. using each of the six plans separately)
      and plan-selection strategy (i.e. selecting one of the three plans depending on
      the fractional gas volume for IMRT and VMAT planning separately). RESULTS: The
      dose difference was approximately linearly correlated to the gas volume
      difference. Underdoses of >3.5% and overdoses of >7% were found for gas volume
      decreases >160 mL/330 mL and increases >260 mL/370 mL for IMRT/VMAT planning,
      respectively. Moreover, for most patients, the single-plan strategy with the use
      of DO = 0.5 resulted in neither undesired underdose nor much overdose. The plan
      selection strategy, however, can always ensure sufficient target coverage and
      minimize high dose regions to the most extent. CONCLUSIONS: The variation in gas
      volume during the treatment course can result in clinically undesired underdose
      or overdose. The DO-based plan-selection strategy can effectively mitigate the
      gas-induced underdose and minimize the overdose for esophageal cancer RT.

PMID- 30289341
TI  - Beyond diagnosis: the relevance of social interactions for participation in
      inclusive preschool settings.
AB  - PURPOSE: This study aims to explore the role of three specific factors within the
      child-environment interaction process - engagement, independence and social
      interactions - in influencing development and learning of children with
      disabilities in inclusive preschool settings. The main question is whether
      children can be categorised in homogenous groups based on engagement,
      independence and social interactions (proximal variables within a biopsychosocial
      framework of human development). The study also examined whether children with
      the same diagnosis would group together or separately, when trying to identify
      clusters of engagement, independence and social interactions, and additionally
      whether such clusters vary as a function of individual child characteristics,
      and/or as a function of structural and process characteristics of preschool
      environment. METHODS: Data was taken from an intervention study conducted in
      mainstream preschools in Portugal. A person-centered cluster analysis was
      conducted to explore group membership of children with various diagnoses, based
      on their engagement, independence and social interaction profiles. RESULTS:
      Results show that children clustered based on similarity of engagement,
      independence and social interaction patterns, rather than on diagnosis. Besides,
      it was found that quality of peer interaction was the only predictor of cluster
      membership. CONCLUSION: These findings support the argument that participation
      profiles may be more informative for intervention purposes than diagnostic
      categories, and that preschool process quality, namely peer interaction, is
      crucial for children's participation.

PMID- 30289343
TI  - Corporate profile: RoosterBio, Inc.
AB  - RoosterBio, Inc. (MD, USA) is a privately held stem cell tools and technology
      company focused on accelerating the development of a sustainable regenerative
      medicine industry, one customer at a time. RoosterBio's products are high-volume
      and well-characterized adult human mesenchymal stem/stromal cells (hMSCs) paired
      with highly engineered media systems. RoosterBio has aimed to simplify and
      standardize how stem cells are purchased, expanded and used in the development of
      regenerative medicine products. To this end, RoosterBio supplies off-the-shelf
      cGMP hMSC working cell banks with bioprocess media that mimic the format and
      formulation of the research grade counterparts, radically simplifying and
      shortening product development and clinical translation. RoosterBio's focus is to
      offer innovative products that help usher in a new era of productivity and
      standardization into the field, with a passion directed towards empowering life
      saving cures to be discovered in regenerative medicine.

PMID- 30289342
TI  - Detection of mixed-strain infections by FACS and ultra-low input genome
      sequencing.
AB  - The epidemiological tracking of a bacterial outbreak may be jeopardized by the
      presence of multiple pathogenic strains in one patient. Nevertheless, this fact
      is not considered in most of the epidemiological studies and only one colony per
      patient is sequenced. On the other hand, the routine whole genome sequencing of
      many isolates from each patient would be costly and unnecessary, because the
      number of strains in a patient is never known a priori. In addition, the result
      would be biased by microbial culture conditions. Herein we propose an approach
      for detecting mixed-strain infection, providing C. difficile infection as an
      example. The cells of the target pathogenic species are collected from the
      bacterial suspension by the fluorescence activated cell sorting (FACS) and a
      shallow genome sequencing is performed. A modified sequencing library preparation
      protocol for low-input DNA samples can be used for low prevalence gut pathogens
      (< 0.1% of the total microbiome). This FACS-seq approach reduces diagnostics time
      (no culture is needed) and may promote discoveries of novel strains.
      Methodological details, possible issues and future directions for the sequencing
      of these natural pan-genomes are herein discussed.

PMID- 30289344
TI  - Total-Laparoscopic Intragastric Surgery for Cardia Endogenous Gastric Submucosal
      Tumors: A Single-Center Short-Term Experience.
AB  - BACKGROUND: Total-laparoscopic intragastric surgery (T-LIGS) has gradually been
      accepted for the treatment of endogenous gastric submucosal tumors. However, it
      is difficult to perform T-LIGS when the tumor is located at the esophagogastric
      junction (cardia endogenous gastric submucosal tumor [CEGSMT]) without special
      laparoscopic instruments that are not available in most developing countries. We
      have successfully treated 12 cases of CEGSMTs using conventional laparoscopic
      instruments and achieved acceptable outcomes. This study was conducted to
      evaluate the surgical techniques for CEGSMT management. METHODS: A retrospective
      analysis was conducted involving all the CEGSMT patients who were treated with T
      LIGS in the General Surgery Department of Guangdong General Hospital from August
      2014 to June 2016. RESULTS: There were 12 patients successfully treated with T
      LIGS. The surgical time ranged from 56 to 108 minutes, and the blood loss was 5
      70 mL. The distance to the tumor from the dentate line was 12-24 mm, and the
      tumor diameter was 17-28 mm. The tumor margins were 9-15 mm, and the eating time
      was 2-4 days. The drainage tube indwelling time was 2-4 days, and the discharge
      time was 4-6 days. The follow-up exams revealed no recurrences, dysphagia, acid
      reflux, or other digestive symptoms. CONCLUSIONS: It is safe and feasible to
      perform T-LIGS using conventional laparoscopic instruments to treat CEGSMTs. We
      suggest that T-LIGS can be performed for endogenous mucosal tumors within 3 cm
      from the cardiac dentate line and less than 3 cm in size.

PMID- 30289345
TI  - The authors reply.
AB  - This is a reply to the commentary of Ossorio and Zhou.

PMID- 30289346
TI  - Clinical Usefulness of a Self-Retaining Internal Organ Retractor for
      Laparoendoscopic Single-Site Adrenalectomy.
AB  - INTRODUCTION: Although laparoendoscopic single-site adrenalectomy (LESS-A) is
      feasible, it is still considered as a challenging procedure because of technical
      limitations. Making an optimal retraction is one of major obstacles in LESS-A,
      and it sometimes requires additional ports or needlescopic devices. Internal
      organ retractor (IOR) is a novel retraction device that is applied
      intracorporeally without additional port. In this study, we investigated the
      clinical usefulness of IOR in LESS-A. MATERIALS AND METHODS: Medical records of
      73 consecutive patients who underwent LESS-A from March 2009 to December 2014
      were reviewed. Twenty-two patients underwent LESS-A with IOR and 51 patients
      without IOR. RESULTS: Mean age, body mass index, tumor size, operation time,
      estimated blood loss, and hospital stay were not significantly different between
      two groups. In IOR group, median number of applied IOR was 2.0 (1.0-3.0) per
      single operation. Mean time for application and removal was 80.0 and 46.5 seconds
      for a single IOR, respectively. There were no complications related to the IOR.
      In without IOR group, there were nine cases that needed needlescopic trocars, six
      cases that needed 5 mm or larger trocars, and one case that was converted to hand
      assisted laparoscopy. However, we did not use any needlescopic instrument or
      additional trocar in IOR group. There was no case of open conversion in both
      groups. CONCLUSION: LESS-A could be done effectively and safely using IOR. IOR
      system maintained optimal retraction throughout the operation. Its application
      and removal are intuitive and take only a few minutes. We think IOR system is an
      attractive retraction method in LESS-A.

PMID- 30289347
TI  - Pump-controlled retrograde trial off: considerations.

PMID- 30289348
TI  - The Use of Theory in Qualitative Research.

PMID- 30289350
TI  - Normothermic ex vivo liver perfusion: platform for liver graft assessment and
      therapeutic modification.
AB  - Liver transplantation as a treatment for end stage liver failure remains limited
      in the United States by the number and quality of donor allografts. Static cold
      storage, the current standard of care for organ storage prior to transplantation,
      offers no method for assessment or therapeutic modification. Cold ischemia and
      its attendant hypoxia deplete cellular adenosine triphosphate (ATP) stores,
      promote cellular damage, and degrade overall organ quality. Normothermic ex vivo
      liver perfusion (NEVLP) offers the potential for assessment of allograft function
      and restoration of intracellular energy stores prior to transplantation. A
      completed phase III randomized trial demonstrated livers undergoing NEVLP prior
      to transplantation demonstrate superior early graft function and less early graft
      dysfunction. NEVLP offers a platform for modification of the allograft via the
      application of defatting or therapeutic cocktails, missense RNA technology, or
      gene editing modalities. The wide versatility of NEVLP appears to be a promising
      tool to expand the current pool of transplantable liver allografts.

PMID- 30289349
TI  - Physician Choice of Hypothyroidism Therapy: Influence of Patient Characteristics.
AB  - BACKGROUND: Most endocrinologists encounter patients who are dissatisfied with
      their current hypothyroidism therapy and request combination therapy with either
      liothyronine (LT3) or thyroid extract. METHODS: A survey of American Thyroid
      Association members was conducted in 2017. Respondents were presented with 13
      scenarios describing patients with hypothyroidism and were asked to choose among
      six therapeutic options. The index patient was satisfied taking levothyroxine
      (LT4) therapy. Twelve variations introduced parameters that potentially provide
      reasons for considering combination therapy (presence of symptoms, low serum
      triiodothyronine concentration, documentation of deiodinase polymorphisms).
      Therapeutic options included (i) continuing LT4, (ii) increasing LT4, (iii)
      adding LT3 to a reduced LT4 dose, (iv) adding LT3 to the current LT4 dose, (v)
      replacing LT4 with thyroid extract, and (vi) replacing LT4 with LT3. Repeated
      measures logistic regression analysis was performed to examine both the
      prescribing of LT4 (options i and ii) versus all other therapies and the choice
      of continuing LT4 (option i) versus either increasing LT4 (option ii), adding LT3
      (options iii and iv), or replacing LT4 with thyroid extract or LT3 (options v and
      vi). RESULTS: Of the 389 survey respondents, 363 physicians prescribed therapy
      for hypothyroidism. For the index patient, 98% of physicians continued current
      LT4 therapy. However, as the patient scenario incorporated other patient
      characteristics, physicians opted to increase LT4 dose or prescribe other
      therapies. The tendency to prescribe alternative therapies was powerfully
      increased by patient symptoms (odds ratio = 25.6 [confidence interval 9-73], p <
      0.0001). Older age and the presence of a comorbidity reduced the likelihood that
      an alternative therapy was prescribed (p = 0.0002 and <0.0001, respectively). All
      other characteristics, except athyreotic status, patient sex, and body mass
      index, significantly increased the likelihood that alternative therapies would be
      prescribed in multivariate analyses (p < 0.0001). CONCLUSIONS: Even with the
      acknowledged limitations of survey methodology, this analysis appears to show a
      marked increase in the willingness of physicians to prescribe combination therapy
      in specific circumstances. If current prescribing patterns do incorporate the use
      of therapies other than LT4, there is a critical need for more research into the
      benefits and risks of these therapies.

PMID- 30289351
TI  - The Application of Pyloric chisel in the Treatment of Hypertrophic Pyloric
      Stenosis by Single-Site Umbilical Laparoscopic Pyloromyotomy.
AB  - OBJECTIVE: The feasibility and perspective of pyloric chisel were discussed
      through the comparison of pyloric chisel and knife in the treatment of
      hypertrophic pyloric stenosis (HPS) in single-site umbilical laparoscopic
      pyloromyotomy (SSULP). METHODS: Fifty-eight cases of HPS treated in our hospital
      from February 2011 to March 2016 were retrospectively analyzed, in which 30
      patients underwent pyloric chisel (Pyloric chisel Group) and 28 patients
      underwent knife (Knife Group). Operative time, estimated blood loss, and
      complications between the two groups were analyzed. RESULTS: The operative time
      was shorter in Pyloric chisel Group than Knife Group (P < .05). The estimated
      blood loss was lower in Pyloric chisel Group than Knife Group (P < .05). The
      complication was less in Pyloric chisel Group than Knife Group (P < .05). There
      were 2 cases of mucosal perforations requiring conversions to open in Knife
      Group. Five cases of serous tearing occurred in the Knife Group. There was 1 case
      of serous tearing in the Pyloric chisel Group. All patients were followed up for
      3 months, and there was no distinct scar in the umbilical. CONCLUSIONS: Patients
      were satisfied with no distinct scars in abdominal wall by pyloric chisel or
      knife to treat HPS in SSULP, but pyloric chisel is more effective and safer.

PMID- 30289353
TI  - Large mediastinal neoplasm penetrating the myocardium.
AB  - A 90-year-old female patient presented to the emergency department with abdominal
      pain. Computed tomography (CT) set the suspicion of a cardiac tumor in the right
      heart chambers. We describe the presentation, the differential diagnosis and the
      decision for management of the patient.

PMID- 30289352
TI  - Galleria mellonella experimental model for bat fungal pathogen Pseudogymnoascus
      destructans and human fungal pathogen Pseudogymnoascus pannorum.
AB  - Laboratory investigations of the pathogenesis of Pseudogymnoascus destructans,
      the fungal causal agent of bat White Nose Syndrome (WNS), presents unique
      challenges due to its growth requirements (4 degrees -15 degrees C) and a lack of
      infectivity in the current disease models. Pseudogymnoascus pannorum is the
      nearest fungal relative of P. destructans with wider psychrophilic -
      physiological growth range, and ability to cause rare skin infections in humans.
      Our broad objectives are to create the molecular toolkit for comparative study of
      P. destructans and P. pannorum pathogenesis. Towards these goals, we report the
      successful development of an invertebrate model in the greater wax moth Galleria
      mellonella. Both P. destructans and P. pannorum caused fatal disease in G.
      mellonella and elicited immune responses and histopathological changes consistent
      with the experimental disease.

PMID- 30289354
TI  - Alpha ketoglutarate levels, regulated by p53 and OGDH, determine autophagy and
      cell fate/apoptosis in response to Nutlin-3a.
AB  - Activated p53 can promote apoptosis or cell cycle arrest. Differences in energy
      metabolism can influence cell fate in response to activated p53. Nutlin-3a is a
      preclinical drug and small molecule activator of p53. Alpha-ketoglutarate
      (alphaKG) levels were reduced in cells sensitive to Nutlin-3a-induced apoptosis
      and increased in cells resistant to this apoptosis. Add-back of a cell-permeable
      alphaKG analog (DMKG) rescued cells from apoptosis in response to Nutlin-3a. OGDH
      is a component of the alphaKGDH complex that converts alphaKG to succinate. OGDH
      knockdown increased endogenous alphaKG levels and also rescued cells from Nutlin
      3a-induced apoptosis. We previously showed reduced autophagy and ATG gene
      expression contributes to Nutlin-3a-induced apoptosis. DMKG and OGDH knockdown
      restored autophagy and ATG gene expression in Nutlin-3a-treated cells. These
      studies indicate alphaKG levels, regulated by p53 and OGDH, determine autophagy
      and apoptosis in response to Nutlin-3a.

PMID- 30289356
TI  - Understanding your body matters: Effects of an entertainment-education serial
      radio drama on fertility awareness in Rwanda.
AB  - Given widespread misunderstanding of pregnancy risk, awareness of one's fertility
      has the potential to influence sexual and reproductive health behaviors. This
      mixed-methods study examined the impact of a serial radio drama in Rwanda, Impano
      n'Impamba, on fertility awareness and other factors related to family planning
      uptake by comparing listeners and non-listeners in a nationally representative
      household survey (n = 1477) and analyzing in-depth interviews with 32 listeners.
      Listeners had higher fertility awareness than non-listeners for key concepts,
      including the menstrual cycle, onset of fertility, and postpartum pregnancy risk.
      Qualitative interviews suggest discussion groups provided an invaluable
      opportunity to ask questions to a knowledgeable facilitator and clarify the
      fertility awareness information. No significant differences in modern family
      planning use or intention to use were found between listeners and non-listeners,
      but listeners reported greater supportive norms, self-efficacy, and discussion of
      family planning. Qualitative interviews suggest that increased discussion about
      family planning occurred because the drama emboldened people to talk about
      uncomfortable and taboo topics. Post-broadcast, listeners of Impano n'Impamba had
      greater fertility awareness then non-listeners and were more likely to experience
      intermediate outcomes related to family planning such as perception of positive
      family planning norms, a feeling of self-efficacy, and increased communication
      with others related to family planning. The study provides lessons for future
      interventions with the aim of increasing fertility awareness to improve sexual
      and reproductive health.

PMID- 30289357
TI  - Combining Two Outcome Frames to Promote Support for Obesity-Related Policies.
AB  - Guided by construal level theory (CLT), this study investigates the interplay
      between two framing approaches that address outcomes of obesity-related policies.
      A randomized experiment (N = 299) was conducted with a 2 (gain- vs. loss-frame) X
      2 (societal- vs. individual-frame) between-participants design. Consistent with
      CLT, frame combinations with consistent construal levels were more persuasive.
      Compared to a societal-loss frame, a societal-gain frame was perceived as a
      stronger argument, which in turn increased policy support. Participants were also
      more likely to engage in healthier diets and physical activity when messages
      highlighted societal-gain rather than societal-loss. This study offers important
      insights for combining multiple framing approaches in a persuasive message to
      improve policy support as well as individual health decisions.

PMID- 30289355
TI  - Infection risk with alemtuzumab decreases over time: pooled analysis of 6-year
      data from the CAMMS223, CARE-MS I, and CARE-MS II studies and the CAMMS03409
      extension study.
AB  - BACKGROUND: Reduced MS disease activity with alemtuzumab versus subcutaneous
      interferon beta-1a (SC IFNB-1a) in core phase 2/3 studies was accompanied by
      increased incidence of infections that were mainly nonserious and responsive to
      treatment. Alemtuzumab efficacy was durable over 6 years. OBJECTIVE: To evaluate
      infections over 6 years in alemtuzumab-treated patients. METHODS: Three
      randomized trials (CAMMS223, Comparison of Alemtuzumab and Rebif Efficacy in
      Multiple Sclerosis (CARE-MS) I, and CARE-MS II) compared two courses of
      alemtuzumab 12 mg with SC IFNB-1a 44 MUg in patients with active relapsing
      remitting MS. An extension study (CAMMS03409) provided further evaluation and as
      needed alemtuzumab retreatment. RESULTS: Infections occurred more frequently with
      alemtuzumab 12 mg than SC IFNB-1a during Years 1 (58.7% vs 41.3%) and 2 (52.6% vs
      37.7%), but declined for alemtuzumab-treated patients in Years 3 (46.6%), 4
      (42.8%), 5 (40.9%), and 6 (38.1%). Serious infections were uncommon (1.0%-1.9%
      per year). Infections were predominantly (>95%) mild to moderate and included
      upper respiratory tract infections, urinary tract infections, and mucocutaneous
      herpetic infections. Prophylactic acyclovir reduced herpetic infections.
      Lymphocyte counts after alemtuzumab therapy did not predict infection risk.
      CONCLUSION: Infections with alemtuzumab were mostly mild to moderate and
      decreased over time, consistent with preservation of components of protective
      immunity.

PMID- 30289358
TI  - Swimmers' Compliance to Training as a Function of Observation: A Pilot Study.
AB  - : Adherence to prescribed training intensity (i.e., swim speed) has been conveyed
      as a key parameter regarding improvements in seasonal performance. Evidence has
      also suggested swimmers have difficulty complying with coach-prescribed training.
      How this compliance is affected by a coaching presence and oversight has yet to
      be examined. PURPOSE: The purpose of this study was to determine swimmers'
      compliance to prescribed training intensity during 3 observational conditions
      using activity monitors. METHOD: Individualized prediction equations were created
      via linear regression analyses for intensity using arm-stroke and leg-kick
      activity counts during a series of seven 91.4-m swim bouts in a group of 17
      collegiate swimmers. Equations were used to calculate intensity performed during
      a standardized training session during which only the observational condition
      varied (e.g., a coach present on deck, no coach present on deck, and an appointed
      observer in addition to the coach present on deck). Compliance was calculated
      from the difference between prescribed training intensity and performed swim
      intensity. Comparisons were made between observed coaching conditions for
      compliance using a repeated-measures analysis of variance. RESULTS: Swimmers'
      compliance to prescribed training intensity during the no-coach condition was
      less compared with the other conditions, including (a) when a coach was present
      and (b) when a coach and an additional observer were present (eta2 = .58).
      CONCLUSION: The presence of a coach or lack thereof appeared to be critical in
      terms of swimmers' compliance to prescribed training intensity. Additional
      observation by nonsupervisory individuals appeared to have no significant effect
      on swimmers' compliance.

PMID- 30289359
TI  - The War Within: Diaries From the Siege of Leningrad.

PMID- 30289360
TI  - Effects of Generalization of Engagement in Parkour from Physical Education to
      Recess on Physical Activity.
AB  - PURPOSE: To investigate the effect of generalization of engagement in parkour
      from physical education (PE) to organized and supervised recess on voluntary
      participation and moderate-to-vigorous physical activity (MVPA). METHOD: Children
      received a 6-day parkour unit in PE and every two lessons they could voluntarily
      participate in 20-min parkour recess. Fourteen elementary school classes
      constituting 281 children (8-10 years old) and 16 PE teachers were randomized to
      either three supervised or three organized parkour recess sessions. During
      supervised recess, PE teachers supervised to ensure safety, and children could
      play freely on the parkour landscape. During organized recess, PE teachers
      provided instructional tasks as well as supervision for safety on the parkour
      landscape. The parkour landscape in the gymnasium was identical in both recess
      conditions and similar to previous parkour landscape in PE. Participation and
      MVPA were measured using systematic observation. RESULTS: Significantly more
      children from organized compared to supervised recess participated in all three
      sessions (60% vs. 43%, p = .008, V = .16). Children showed significantly less
      sedentary behavior (24% vs. 30%, p = .013, eta2 = .063) and more MVPA (76% vs.
      70%, p = .012, eta2 = .066) during organized compared to supervised recess. The
      proportion of total MVPA spent doing parkour was significantly higher in
      organized compared to supervised recess for low- (36% vs. 24%, p = .005, eta2 =
      .082) and high-skilled children (33% vs. 26%, p = .034, eta2 = .048). CONCLUSION:
      Generalization of engagement in parkour was higher in organized compared to
      supervised recess.

PMID- 30289361
TI  - Richmond Barthe: Black Homoeroticism and the Raptures of the Hermaphroditic Body.
AB  - African American sculptor Richmond Barthe (1901-1989) conjoined issues of
      sexuality and race in works that foreground the aesthetic worth of Black bodies.
      While exposing Western figuration practices that exclude Black people from
      artistic visibility, Barthe also targeted the African American distaste for the
      explicit treatment of nudity. Barthe's androgynous sculptures have by now become
      the trademark of his art, but Barthesian scholarship still neglects the
      significance of a small group of statues, which de-emphasize the aura of same-sex
      desire, in order to explore the intricacies of corporeal ambisexuality. In view
      of his homoerotic depictions and the presence of the hermaphrodite at the core of
      his disruption of the sexual dichotomy, the frequent assumption that Barthe
      remained "closeted all his life" does not stand critical scrutiny. Instead of
      taking refuge in the sexual closet, Barthe debunked the man/woman binary as the
      foremost epistemic construct that prompts the societal need for sexual self
      misrepresentations.

PMID- 30289362
TI  - Second-generation Western Muslims: A qualitative analysis of multiple social
      identities.
AB  - The relationships between social identities are important when discussing the
      national and religious identities of Muslims in Western contexts. This study
      explored the identity narratives of second-generation Muslim young adults to
      consider the relevance of bicultural identity and acculturation theories commonly
      employed in research with this group. The sample comprised 20 Muslim young adults
      of diverse ethnicities and backgrounds from Montreal, Berlin, and Copenhagen who
      participated in semi-structured interviews that explored how they negotiate their
      social identities in light of their unique life course trajectories. This article
      focuses on two major themes underlying second-generation identity development:
      the importance of personal experience in the development of social identities;
      and the enmeshment of multiple social identities. We then discuss the results of
      our findings in light of the complex nature of social identity, group membership,
      and political categorization.

PMID- 30289363
TI  - Disconnectomics: Stroke-related disconnection and dysfunction in distributed
      brain networks.
AB  - Modern clinical neuroscience was built on observations of how localized damage
      caused specific functional, cognitive and behavioral deficits. Stroke neurology
      was a cornerstone of understanding this functional specialization in the brain.
      But most lesion-symptom mapping provides little prognostic value above clinical
      observations. Stroke topography remains a poor indicator of long-term outcome,
      and with stroke a major risk factor for dementia, there is strong incentive to
      find markers of predictive value. There is now growing recognition that the
      damage caused by stroke does not occur in isolation but is embedded within a
      complex, highly interconnected, organized and dynamic system: the connectome.
      Early theories of the widespread effect of focal lesions are resurfacing, buoyed
      by sophisticated new methods and large-scale data sets. As with all emerging
      methods and technologies, there may be healthy skepticism as to the
      appropriateness of the method to the population under investigation or doubt that
      connectivity-derived metrics will ever be clinically translatable. While we
      acknowledge that there remain significant technical challenges to overcome, we
      argue that the methods provide real potential to illuminate our understanding of
      the widespread effects and clinical syndromes that can arise from diverse focal
      damage.

PMID- 30289364
TI  - Profiles of Trauma in Primary and Permanent Teeth of Children and Adolescents.
AB  - This retrospective study aimed to evaluate the dental trauma profile in primary
      and permanent teeth from patients between 0 and 15 years old who attended the
      Faculty of Dentistry of the Federal University of Rio de Janeiro. Data regarding
      gender, age, trauma classification, tooth type, and affected tissues were
      obtained from dental records. The data were analyzed descriptively and by the
      chi2 test (p < 0.05). Data associated with 333 traumatized teeth (70% primary and
      30% permanent teeth) were included. The mean ages of children with affected
      primary and permanent teeth were 3.35 +/- 2.02 and 9.09 +/- 2.43 years,
      respectively. Males presented more permanent teeth with trauma (64.4%) than
      primary ones (55.6%; p = 0.085). The upper central incisors, both primary (68.9%)
      and permanent (69.4%), were the teeth most commonly affected. Primary teeth
      showed a higher frequency (p < 0.001) of supportive tissue trauma (73.3%) and
      lower frequency (p = 0.001) of hard tissue trauma (40.7%) than those in permanent
      ones (51.5% and 60.6%, respectively). The most frequent trauma in the supportive
      tissue was subluxation (27.2%) and permanent lateral luxation (42.0%). In the
      hard tissues, permanent teeth presented a higher prevalence of trauma than
      primary ones (p = 0.001), however this difference was not statistical significant
      when each type of fracture injury was evaluated individually (p > 0.005). With
      affected primary teeth, there was a greater frequency of trauma in the gingival
      mucosa (31.0%; p = 0.022); in the permanent ones, traumatic lesions in the chin
      region were the most prevalent (20.8%; p = 0.009). Trauma was recurrent in 26.3%
      of primary teeth and in 20.2% permanent teeth. Therefore, primary and permanent
      teeth showed distinct trauma profiles, suggesting that distinct preventive and
      therapeutic approaches are needed for these two groups.

PMID- 30289365
TI  - Clinical and Radiographic Evaluation of Formocresol and Chloramphenicol,
      Tetracycline and Zinc Oxide-Eugenol Antibiotic Paste in Primary Teeth
      Pulpotomies: 24 month follow up.
AB  - OBJECTIVE: The purpose of the present study was to evaluate clinically and
      radiographically the effectiveness of formocresol and the antibiotic paste CTZ
      (chloramphenicol, tetracycline and zinc oxide-eugenol) in primary teeth
      pulpotomies, during a 6, 12 and 24 month period. STUDY DESIGN: A total of 80
      pulpotomies were performed in 58 patients between three and six years of age. The
      patients were selected and assigned to two groups: Group I Formocresol (FC,
      n=40), Group II chloramphenicol-tetracycline-zinc oxide eugenol (CTZ, n=40). The
      teeth were restored with glass ionomer and pre-formed stainless steel crowns. The
      treated teeth were evaluated clinically and radiographically at 6, 12 and 24
      months. RESULTS: After 24 months of follow up a 100% and 94.3% clinical success
      was obtained, in the CTZ and formocresol groups respectively (x2= 0.450, p>0.05).
      The radiographic success was of 97.4% and 94.3% respectively (x2= 0.920, p>0.05).
      CONCLUSION: The performance of the antibiotic paste CTZ was superior to
      formocresol. No statistically significant differences were observed between the
      treatment groups either clinically or radiographically. More randomized clinical
      trials should be performed before it can be indicated safely.

PMID- 30289366
TI  - Salivary Factors Related to Caries in Children with Autism.
AB  - : Many predisposing factors to caries are present in autism, however, it is
      unlikely that autistic patients exhibit higher caries indexes than the rest of
      the population. OBJECTIVE: To evaluate salivary factors related to caries in
      autistic patients. STUDY DESIGN: 34 autistics and 34 controls aged between 4-13
      years old were included. Decayed, missing, and filled teeth (DMFT) index and oral
      hygiene simplified index (IHO-S) were assessed, as well as, pH, total proteins,
      phosphate, calcium and IgA in saliva. All data were analyzed by chi2 and Student
      t tests for independent samples. P values<0.05 were considered statistically
      significant. RESULTS: Autistic patients showed less caries than controls
      (p<=0.001), DMFT was 1+/-1 and 3+/-2 respectively (p<=0.001). In relation to IHO
      S, values increased (p=0.008) in autistic patients (2.25+/-0.78) compared to
      controls (1.79+/-0.59), however Salivary ph means were similar (7.20+/-0.48 and
      7.27+/-0.34 respectively). Decreased calcium levels (p=0.013) were observed in
      autistics (0.621+/-0.35 mmol/L) compared to controls (0.89+/-0.51 mmol/L), but
      phosphate levels were similar (6.17+/-4.22 M, 5.51+/-4.86 M respectively). When
      total proteins of saliva were assessed, autistics showed a slight increment
      (2.65+/-1.81 mg/mL) compared to controls (2.24+/-1.27 mg/mL) and zymography
      showed a higher proteolytic activity in autistic children. Finally, IgA
      concentration reached 116.55+/-90.97 MUg/mL in autistics and 161.61 +/-
      193.37MUg/mL (p=0.527) in the control group. CONCLUSIONS: Even though patients
      with autism exhibited a poorer oral hygiene, caries indexes were lower, calcium
      levels in saliva were found to be lesser and phosphate levels higher.

PMID- 30289367
TI  - Posterior Available Space for Uprighting Horizontally Impacted Mandibular Second
      Molars Using Orthodontic Microimplant Anchorage.
AB  - Treatment of horizontally and deeply impacted mandibular molars is challenging
      for both orthodontists and oral surgeons because of the limited access and
      anchorage control. We report on two patients who had horizontally and mesially
      impacted mandibular second molars (MM2s). Both patients were treated by a
      surgical orthodontic approach, and the crowns of the impacted teeth were brought
      into the arches by closed forced eruption. Mesially impacted MM2s were uprighted
      with orthodontic microimplants, inserted in the retromolar area, and then moved
      into their ideal position. The first patient was in an active growing stage,
      while the second patient was beyond the active growing stage. Therefore posterior
      available space (PAS) should be analyzed before treatment of impacted MM2s to
      prevent periodontal problems after uprighting of impacted teeth. If PAS is not
      enough for uprighting impacted MM2s, alternative treatment should be considered
      based on the stage of growth.

PMID- 30289368
TI  - Fluoride Intake of Infants from Formula.
AB  - OBJECTIVE: This study aimed to assess fluoride intake in infants from formula
      reconstituted with water, with fluorosis risk in mind. STUDY DESIGN: Data on
      water source, formula brand/type, volume of formula consumption and infant weight
      were collected for infants at two-, four-, six-, nine- and twelve-month
      pediatrician well child visits. Identified formula brands and water types were
      reconstituted and analyzed for fluoride concentration. Patient body mass and
      volume consumed/day were used to estimate fluoride intake from reconstituted
      formula. Descriptive statistics, one-way analysis of variance and chi-square
      tests were utilized. RESULTS: All infants consumed formula reconstituted with
      minimally fluoridated water (0.0- 0.3 ppm). 4.4% of infants exceeded the
      recommended upper limit (UL) of 0.1mg/kg/day. Although mean daily fluoride
      consumption significantly differed among all groups, the proportion of infants at
      each visit milestone that exceeded daily fluoride intake of 0.1mg/kg/day was not
      statistically significantly different (p>0.05) for any age group. Predicted
      values calculated with optimally fluoridated water (0.7ppm) resulted in 36.8% of
      infants exceeding the UL. CONCLUSIONS: Optimally fluoridated water may increase
      fluorosis risk for patients younger than six months. Future investigation should
      include multiple sites and multi-year follow-up to assess actual fluorosis
      incidence.

PMID- 30289369
TI  - Titanium Dioxide Nanoparticles and Cetylpyridinium Chloride Enriched Glass
      Ionomer Restorative Cement: A Comparative Study Assessing Compressive Strength
      and Antibacterial Activity.
AB  - OBJECTIVE: To evaluate the addition of titanium dioxide (TiO2) nanoparticles and
      cetylpyridinium chloride (CPC) on the compressive strength and antibacterial
      activity of conventional glass-ionomer cement (GIC). STUDY DESIGN: TiO2
      nanoparticles enriched GIC was prepared by adding 3% TiO2 nanoparticles (w/w)
      into the powder component of conventional GIC. CPC containing GIC was developed
      by incorporating 1% CPC (w/w) into conventional GIC powder. Samples were
      segregated into three groups: GIC with 3% TiO2 nanoparticles, GIC with 1% CPC and
      unmodified conventional GIC. Compressive strength was assessed using the
      universal testing machine on cylindrical specimens made from each material.
      Antibacterial activity was assessed by measuring inhibition zones on Mitis
      Salivarius Bacitracin (MSB) agar inoculated with pure strain of Streptococcus
      mutans (S. mutans). RESULTS: GIC containing TiO2 nanoparticles exhibited
      significantly greater compressive strength as compared with CPC and conventional
      GIC groups (P < 0.01). However, there was no significant difference between the
      compressive strengths of CPC and conventional GIC group (P >0.05). Antibacterial
      activity was significantly greater for TiO2 group than conventional GIC (P
      <0.05). CPC increased the antibacterial activity of conventional GIC, though not
      significantly. CONCLUSION: The addition of 3% TiO2 nanoparticles improves the
      compressive strength of GIC as well as its antibacterial activity against S.
      mutans.

PMID- 30289370
TI  - Oral Manifestations of Autoimmune Neutropenia: A Case Report.
AB  - Autoimmune neutropenia is a self-limiting condition characterized by the presence
      of granulocyte-specific autoantibodies. This case report describes a 2-year-old
      female who presented to the Department of Pediatric Dentistry with a history of
      oral ulceration, complicated by high temperature, gingival hypertrophy and
      gingival hemorrhage. These symptoms had precipitated an admission to a district
      general hospital and diagnosis of viral tonsillitis. The severity of the
      presentation to the Pediatric Dental Department prompted a review of recent
      discharge blood investigations, which revealed a neutrophil count of
      0.07*109/L(1.0-8.5 *109/L) indicating severe neutropenia. Urgent referral to
      Pediatric Hematology resulted in same-day admission and a diagnosis of autoimmune
      neutropenia was established. The patient was managed with chlorhexidine
      mouthwash, prophylactic antimicrobial and antifungal medication and granulocyte
      colony stimulating factor (G-CSF). Neutropenia may present with features
      exclusive to the oral cavity. Recognition of atypical presentations such as oral
      ulceration with associated systemic illness may assist in early diagnosis.

PMID- 30289371
TI  - Preemptive Analgesia by Paracetamol, Ibuprofen or Placebo in Pediatric Dental
      Care: A Randomized Controlled Study.
AB  - OBJECTIVE: To compare postoperative pain among children who received an oral dose
      of paracetamol, ibuprofen or a placebo, prior to tooth extractions. STUDY DESIGN:
      Thirty minutes prior to dental treatment, children received a liquid dosage,
      fruit flavored and orange colored, of paracetamol, ibuprofen, or a placebo. Data
      accessed included children's dental history, their behavior, and their feeling of
      pain or anxiety according to Wong-Baker FACES: before treatment, following local
      anesthesia, and following treatment. Parents were interviewed by telephone
      regarding their children's need for a postoperative analgesia (paracetamol or
      ibuprofen), and their feeling of pain at four and 24 hours posttreatment.
      RESULTS: Parents reported administering paracetamol or nurofen following the
      dental procedure to 9/43 (21%), 2/33 (6%) and 12/29 (41%) of the children in the
      preemptive paracetamol, ibuprofen, and placebo groups, respectively. For the 3
      groups, mean pain assessment were similar: around the middle of the Wong-Baker
      FACES scale at baseline, slightly higher following local anesthesia, and low
      (pain-free) at four and 24 hours postoperative. CONCLUSION: Children who received
      paracetamol or ibuprofen prior to tooth extractions were less likely to need an
      analgesic following treatment, compared to children who received a placebo.

PMID- 30289372
TI  - A person-centered analysis of sleep and emotion dysregulation: Short- and long
      term links with depression and alcohol use.
AB  - OBJECTIVE: Our objective was to examine the co-occurrence of sleep problems and
      emotion dysregulation and its short- and long-term links to depressive symptoms
      and alcohol use in a sample of university students. METHOD: Participants included
      1132 first-year university students from Southern Ontario (70.5% women). Time 1
      data were collected in February/March, 2010, and Time 2 data (n = 746) were
      collected in February/March, 2014. Participants were surveyed about sleep
      problems and emotion dysregulation (Time 1), and depressive symptoms and alcohol
      use (Times 1 and 2). RESULTS: A latent class analysis revealed four groups: (1)
      Low Co-Occurrence, (2) Sleep Problems Only, (3) Emotion Dysregulation Only, and
      (4) High Co-occurrence. Group 4 had more depressive symptoms than all other
      groups in both the short- and long-term. CONCLUSIONS: First year university
      students with high co-occurrence of sleep problems and emotion dysregulation may
      be a target group for programs focused on reducing adjustment difficulties.

PMID- 30289373
TI  - Baby Boomer's Substance Abuse and Researcher Indifference.
AB  - The current older adult population is more likely to need and seek treatment for
      alcohol and drug abuse than previous cohorts of older adults, which necessitates
      the need for age-appropriate substance use treatment. Building on previous
      research that examined the lack of attention on substance use among older adults,
      this study examines articles addressing substance use disorders among older
      adults in leading gerontological and substance abuse journals and federal funding
      between 2011 and 2017. Publications were identified from ten leading
      gerontological and ten leading substance abuse journals using Medical Subject
      Heading (MeSH) terms. During this time-period, there were 68 and 44 articles
      published in gerontology and substance abuse journals respectively related to
      substance use disorders in older adults. Most (59.8%) addressed alcohol abuse and
      7% involved intervention studies. In the 7-year period, there were 13 federal
      grants. A paucity of published or funded work exists in this area despite growing
      misuse and treatment seeking among older adults with substance use disorders.
      Effectively addressing substance abuse in older adults will require a coordinated
      effort between researchers and practitioners to establish and implement best
      practices for practitioners to rely on when working with substance abusing older
      adults.

PMID- 30289374
TI  - Building resilient families: Developing family interventions for preventing
      adolescent depression and HIV in low resource settings.
AB  - Depression contributes significantly to the global burden of disease in low- and
      middle-income countries. In South Africa, individuals may be at elevated risk for
      depression due to HIV and AIDS, violence, and poverty. For adolescents,
      resilience-focused prevention strategies have the potential to reduce onset of
      depression. Involving families in promoting adolescent mental health is
      developmentally appropriate, but few existing interventions take a family
      approach to prevention of adolescent depression. We conducted a qualitative
      investigation from 2013-2015 to inform the development of a family intervention
      to prevent adolescent depression in South Africa among families infected or at
      risk for HIV. Using focus groups with adolescents and parents (eight groups, n =
      57), and interviews (n = 25) with clinicians, researchers, and others providing
      mental health and related services, we identified context-specific factors
      related to risk for family depression, and explored family interactions around
      mental health more broadly as well as depression specifically. Findings indicate
      that HIV and poverty are important risk factors for depression. Future
      interventions must address linguistic complexities in describing and discussing
      depression, and engage with the social interpretations and meanings placed upon
      depression in the South African context, including bewitchment and deviations
      from prescribed social roles. Participants identified family meetings as a
      context-appropriate prevention strategy. Family meetings offer opportunities to
      practice family problem solving, involve other family members in communal
      parenting during periods of parental depression, and serve as forums for building
      Xhosa-specific interpretations of resilience. This study will guide the
      development of Our Family Our Future, a resilience-focused family intervention to
      prevent adolescent depression (ClinicalTrials.gov #NCT02432352).

PMID- 30289376
TI  - A study on the potential use of paper sludge ash in concrete with glass
      aggregate.
AB  - This short communication focuses on the potential use of paper sludge ash, a
      waste product of the paper making industry, as an innovative binder partially
      replacing cement in concrete with glass aggregate. After preliminary testing
      using binary or ternary CEM-II mixes with paper sludge ash/pulverised fly ash, a
      suitable mix for concrete with glass aggregate was identified. Concrete mixes
      with partial or full natural sand replacement by waste glass aggregate were then
      produced and showed appropriate strengths and overall similar or better water
      absorption characteristics than control mixes with natural aggregates, without
      manifest alkali-silica reaction problems. This shows potential for applications
      in precast dry mix concrete units based on the required strengths that were
      achieved.

PMID- 30289375
TI  - HcPT1.2 participates in Pi acquisition in Hebeloma cylindrosporum external hyphae
      of ectomycorrhizas under high and low phosphate conditions.
AB  - Ectomycorrhizal fungi improve tree phosphorus nutrition through transporters
      specifically localized at soil-hyphae and symbiotic interfaces. In the model
      symbiosis between the fungus Hebeloma cylindrosporum and the maritime pine (Pinus
      pinaster), several transporters possibly involved in phosphate fluxes were
      identified, including three H+:Pi transporters. Among these three, we recently
      unraveled the function of one of them, named HcPT2, in both pure culture and
      symbiotic interaction with P. pinaster. Here we investigated the transporter
      named HcPT1.2, by analyzing inorganic phosphate transport ability in a yeast
      complementation assay, assessing its expression in the fungus associated or not
      with the plant, and immunolocalizing the proteins in ectomycorrhizas. We also
      evaluated the effect of external Pi concentration on expression and localization
      of HcPT1.2. Our results revealed that HcPT1.2 is involved in Pi acquisition by H.
      cylindrosporum mycelium, irrespective of the external Pi concentrations.

PMID- 30289377
TI  - Lux in Tenebris: The Visual and the Symbolic in Western Esotericism.

PMID- 30289378
TI  - Engineering resistance against Tomato yellow leaf curl virus via the CRISPR/Cas9
      system in tomato.
AB  - CRISPR/Cas systems confer molecular immunity against phages and conjugative
      plasmids in prokaryotes. Recently, CRISPR/Cas9 systems have been used to confer
      interference against eukaryotic viruses. Here, we engineered Nicotiana
      benthamiana and tomato (Solanum lycopersicum) plants with the CRISPR/Cas9 system
      to confer immunity against the Tomato yellow leaf curl virus (TYLCV). Targeting
      the TYLCV genome with Cas9-single guide RNA at the sequences encoding the coat
      protein (CP) or replicase (Rep) resulted in efficient virus interference, as
      evidenced by low accumulation of the TYLCV DNA genome in the transgenic plants.
      The CRISPR/Cas9-based immunity remained active across multiple generations in the
      N. benthamiana and tomato plants. Together, our results confirmed the efficiency
      of the CRISPR/Cas9 system for stable engineering of TYLCV resistance in N.
      benthamiana and tomato, and opens the possibilities of engineering virus
      resistance against single and multiple infectious viruses in other crops.

PMID- 30289379
TI  - Insights into microbiome research 2: Experimental design, sample collection, and
      shipment.
AB  - Conducting a robust experiment is not trivial in microbiome research, and as with
      any study, experimental methods, environmental factors, and analysis methods can
      affect results. Standards for data collection and analysis are still emerging in
      the field, and notably, many of the most fundamental issues that concern
      microbiome studies arise from statistical and experimental design issues. The
      most important challenge for the field is to integrate new approaches that are
      unique to microbiome studies, while remembering standard practices that are
      broadly applicable to all scientific studies. In this section, attention is
      focused on sample collection, storage and shipping of microbiome-related samples,
      and how careful, purposeful design can increase the statistical power of these
      studies.

PMID- 30289380
TI  - 2018 Editors' commentary.

PMID- 30289381
TI  - Hormone dependent survival mechanisms of plants during post-waterlogging stress.
AB  - Waterlogging stress has two phases like waterlogging phase and post-waterlogging
      phase where both are injurious to plants. Susceptible plants normally die at post
      waterlogging phase due to damaged root system, sudden rexoygenation, dehydration
      and photoinhibition of the desubmerged tissues. Formation of reactive oxygen
      species (ROS) is the main result of reoxygenation stress that can cause oxidative
      damage of the functional tissues responsible for normal physiological activities.
      There are almost all types of hormones responsible to recover plants from these
      destructive phenomenons. Among these hormones ethylene and abscisic acid (ABA)
      are the main regulators to overcome the reoxygenation and drought like stresses
      in plants at post-waterlogging condition. The balanced crosstalk among the
      hormones is highly important for the survival of plants at these stresses. So
      this paper is completely a precise summary of hormonal homeostasis of post
      waterlogged plants through physiological, biochemical and signaling pathways.

PMID- 30289382
TI  - Meat and fat quality of Krskopolje pigs reared in conventional and organic
      production systems.
AB  - Data on production traits of the only Slovenian autochthonous pig breed, the
      Krskopolje pig, is very scarce. Krskopolje pigs are reared in conventional and
      organic production systems, which were compared in the present study. After
      weaning, 24 barrows were assigned within litter to either conventional (CON) or
      organic (ECO) rearing system. Group CON (n=12) was housed indoors in two pens
      (7.5 m2) with partly slatted floor. Group ECO (n=12) was held in a sty with
      sheltered area (concrete floor, bedded with straw, 16 m2) and outdoor paddock
      area (100 m2). The trial started when pigs had 68+/-8 kg BW and 157+/-6 days of
      age. Two diets were formulated with equivalent ingredients and composition. For
      ECO diet the ingredients used were ecological. Group ECO received a diet with
      12.4 MJ metabolisable energy (ME) per kilogram and 12.9% CP and group CON a diet
      with 12.7 MJ ME/kg and 13.6% CP. Feed distribution was limited to 3.5 kg per pig
      daily. In line with the rules for organic production, ECO pigs were additionally
      given alfalfa hay ad libitum. After 73 days on trial, the pigs were slaughtered
      and carcass, meat and fat quality was evaluated. Meat quality traits (pH, colour,
      water holding capacity), fatty acid composition, lipid and protein oxidation,
      collagen content and solubility were analysed in longissimus lumborum (LL)
      muscle. Fatty acid composition, lipid oxidation, and vitamins A and E
      concentrations were determined in backfat. There were no significant differences
      in growth rate and carcass traits between ECO and CON pigs, however, ECO pigs
      tended (P<0.10) to have higher daily gain and lower dressing percentage, higher
      (P<0.001) pH 45 min and lower (P<0.01) pH 24 h postmortem, affecting (P<0.10)
      also water holding capacity and objective colour parameters (P<0.05) of LL
      muscle. There were no differences in intramuscular fat (IMF) content of LL
      muscle, however, IMF of ECO pigs had lower (P<0.05) proportion of saturated and
      higher (P<0.01) proportion of monounsaturated fatty acids accompanied by higher
      (P<0.001) values of thiobarbituric reactive substances (TBARS). In backfat, ECO
      pigs showed lower (P<0.05) vitamin E content, higher (P<0.001) TBARS, higher
      (P<0.01) degree of unsaturation (percentage of polyunsaturated fatty acids), and
      also higher (P<0.05) vitamin A concentration than CON pigs, which can be related
      to alfalfa hay supplementation of ECO pigs. In brief, organic rearing of
      Krskopolje pigs did not affect performances but had an effect on meat and fat
      quality.

PMID- 30289383
TI  - A carbapenem-resistant clinical isolate of Aeromonas hydrophila in Japan
      harbouring an acquired gene encoding GES-24 beta-lactamase.
AB  - Several species of Aeromonas produce the enzyme CphA metallo-beta-lactamase. This
      study describes an isolate of Aeromonas hydrophila harbouring an acquired gene
      encoding the carbapenemase GES-24. This isolate was obtained from an inpatient in
      Okinawa, Japan, with no apparent record of travelling overseas. The minimum
      inhibitory concentrations of carbapenems against this isolate were 8 ug ml-1 for
      imipenem and 16 ug ml-1 for meropenem. Recombinant GES-24 hydrolyzed all of the
      tested beta-lactams, including imipenem and meropenem. The genomic environment
      surrounding blaGES-24 was intI1-blaGES-24-aac(6')-IIc-qacEdelta1-sulI-orfX-tetR
      tetE. This is the first report of A. hydrophila producing a GES-type
      carbapenemase.

PMID- 30289384
TI  - The decoration of specialized metabolites influences stylar development.
AB  - Plants produce many different specialized (secondary) metabolites that function
      in solving ecological challenges; few are known to function in growth or other
      primary processes. 17-Hydroxygeranylinalool diterpene glycosides (DTGs) are
      abundant herbivory-induced, structurally diverse and commonly malonylated defense
      metabolites in Nicotiana attenuata plants. By identifying and silencing a
      malonyltransferase, NaMaT1, involved in DTG malonylation, we found that DTG
      malonylation percentages are normally remarkably uniform, but when disrupted,
      result in DTG-dependent reduced floral style lengths, which in turn result from
      reduced stylar cell sizes, IAA contents, and YUC activity; phenotypes that could
      be restored by IAA supplementation or by silencing the DTG pathway. Moreover, the
      Nicotiana genus-specific JA-deficient short-style phenotype also results from
      alterations in DTG malonylation patterns. Decorations of plant specialized
      metabolites can be tuned to remarkably uniform levels, and this regulation plays
      a central but poorly understood role in controlling the development of specific
      plant parts, such as floral styles.

PMID- 30289385
TI  - Crystal structure of the full Swi2/Snf2 remodeler Mot1 in the resting state.
AB  - Swi2/Snf2 ATPases remodel protein:DNA complexes in all of the fundamental
      chromosome-associated processes. The single-subunit remodeler Mot1 dissociates
      TATA box-binding protein (TBP):DNA complexes and provides a simple model for
      obtaining structural insights into the action of Swi2/Snf2 ATPases. Previously we
      reported how the N-terminal domain of Mot1 binds TBP, NC2 and DNA, but the
      location of the C-terminal ATPase domain remained unclear (Butryn et al., 2015).
      Here, we report the crystal structure of the near full-length Mot1 from
      Chaetomium thermophilum. Our data show that Mot1 adopts a ring like structure
      with a catalytically inactive resting state of the ATPase. Biochemical analysis
      suggests that TBP binding switches Mot1 into an ATP hydrolysis-competent
      conformation. Combined with our previous results, these data significantly
      improve the structural model for the complete Mot1:TBP:DNA complex and suggest a
      general mechanism for Mot1 action.

PMID- 30289386
TI  - Simulation of spontaneous G protein activation reveals a new intermediate driving
      GDP unbinding.
AB  - Activation of heterotrimeric G proteins is a key step in many signaling cascades.
      However, a complete mechanism for this process, which requires allosteric
      communication between binding sites that are ~30 A apart, remains elusive. We
      construct an atomically detailed model of G protein activation by combining three
      powerful computational methods: metadynamics, Markov state models (MSMs), and
      CARDS analysis of correlated motions. We uncover a mechanism that is consistent
      with a wide variety of structural and biochemical data. Surprisingly, the rate
      limiting step for GDP release correlates with tilting rather than translation of
      the GPCR-binding helix 5. beta-Strands 1 - 3 and helix 1 emerge as hubs in the
      allosteric network that links conformational changes in the GPCR-binding site to
      disordering of the distal nucleotide-binding site and consequent GDP release. Our
      approach and insights provide foundations for understanding disease-implicated G
      protein mutants, illuminating slow events in allosteric networks, and examining
      unbinding processes with slow off-rates.

PMID- 30289387
TI  - Feedback optimizes neural coding and perception of natural stimuli.
AB  - Growing evidence suggests that sensory neurons achieve optimal encoding by
      matching their tuning properties to the natural stimulus statistics. However, the
      underlying mechanisms remain unclear. Here we demonstrate that feedback pathways
      from higher brain areas mediate optimized encoding of naturalistic stimuli via
      temporal whitening in the weakly electric fish Apteronotus leptorhynchus. While
      one source of direct feedback uniformly enhances neural responses, a separate
      source of indirect feedback selectively attenuates responses to low frequencies,
      thus creating a high-pass neural tuning curve that opposes the decaying spectral
      power of natural stimuli. Additionally, we recorded from two populations of
      higher brain neurons responsible for the direct and indirect descending inputs.
      While one population displayed broadband tuning, the other displayed high-pass
      tuning and thus performed temporal whitening. Hence, our results demonstrate a
      novel function for descending input in optimizing neural responses to sensory
      input through temporal whitening that is likely to be conserved across systems
      and species.

PMID- 30289388
TI  - The ectodomains determine ligand function in vivo and selectivity of DLL1 and
      DLL4 toward NOTCH1 and NOTCH2 in vitro.
AB  - DLL1 and DLL4 are Notch ligands with high structural similarity but context
      dependent functional differences. Here, we analyze their functional divergence
      using cellular co-culture assays, biochemical studies, and in vivo experiments.
      DLL1 and DLL4 activate NOTCH1 and NOTCH2 differently in cell-based assays and
      this discriminating potential lies in the region between the N-terminus and EGF
      repeat three. Mice expressing chimeric ligands indicate that the ectodomains
      dictate ligand function during somitogenesis, and that during myogenesis even
      regions C-terminal to EGF3 are interchangeable. Substitution of NOTCH1-interface
      residues in the MNNL and DSL domains of DLL1 with the corresponding amino acids
      of DLL4, however, does not disrupt DLL1 function in vivo. Collectively, our data
      show that DLL4 preferentially activates NOTCH1 over NOTCH2, whereas DLL1 is
      equally effective in activating NOTCH1 and NOTCH2, establishing that the
      ectodomains dictate selective ligand function in vivo, and that features outside
      the known binding interface contribute to their differences.

PMID- 30289390
TI  - Laparoscopic splenectomy and azygoportal disconnection combining with pre- and
      postoperative endoscopic intervention - A sandwich-style sequential therapy for
      portal hypertensive bleeding: A retrospective cohort study.
AB  - BACKGROUND/AIMS: In patients who survive the first esophageal variceal bleeding
      (EVB) resulting from portal hypertension, the probability of fatal esophageal
      variceal re-bleeding (EVR) is high. We have developed a sandwich-style sequential
      therapy combining laparoscopic splenectomy and azygoportal disconnection (LSD)
      with preoperative and postoperative endoscopic intervention (LSDE). The aim of
      the present study was to investigate whether LSDE is safe and effective and to
      evaluate whether the postoperative EVR rate for LSDE was lower than that for LSD
      without periodical postoperative endoscopic intervention (NLSDE). MATERIALS AND
      METHODS: We retrospectively investigated the outcomes of 226 patients with
      cirrhosis with EVB and secondary hypersplenism who all received preoperative
      endoscopic variceal ligation (EVL) to manage emergency EVB then underwent NLSDE
      (n=106) or LSDE (n=120) between February 2012 and April 2016. The perioperative
      and follow-up variables of the two groups were evaluated. RESULTS: Between the
      two groups, there were no differences in number of blood transfusions,
      intraoperative blood loss, postoperative complications, and hospital stay. LSDE
      showed shorter operation time (p=0.001) and lower EVR rates during the periods
      ranging from 1 to 12 months, 4 to 6 months, 4 to 12 months, and 7 to 12 months
      (all p<0.05) than NLSDE. Dynamic changes in the diameter of the esophageal
      varices and the rates of EVL in the LSDE group both decreased gradually and
      significantly over the 12-month follow-up period (all p<0.0001). CONCLUSION:
      Laparoscopic splenectomy and azygoportal disconnection with periodical
      postoperative endoscopy is safe and effective for reducing the EVR rate in
      cirrhotic portal hypertension.

PMID- 30289391
TI  - Predictors of poor outcomes in 488 patients with herbinduced liver injury.
AB  - BACKGROUND/AIMS: Herb-induced liver injury (HILI) can lead to chronic liver
      injury, liver transplantation, or even death. This study aimed to identify the
      predictors of poor HILI outcomes, especially chronic HILI. MATERIALS AND METHODS:
      Clinical data of 488 patients with HILI were retrospectively analyzed from a
      Chinese center between January 2010 and January 2014. Logistic regression and C
      statistic were used to identify risk factors and prognostic models for HILI
      outcomes. RESULTS: In all patients, 69 (14.1%) developed chronic HILI, and 20
      (4.1%) died due to liver injury or underwent liver transplantation. To predict
      the fatal HILI prognosis, the model for end-stage liver disease (MELD) with a C
      statistic of 0.981 (95%CI 0.968-0.995) was better than Hy's law (C-statistic
      0.569; 95%CI 0.449-0.689). The latency, course of peak alanine aminotransferase
      decreasing >=50% after discontinuation of herb application, peak triglyceride
      value, and platelet count at liver injury onset were identified as independent
      risk factors for chronicity with the adjusted odds ratios of 1.268 (95%
      confidence interval [CI] 1.034-1.554), 2.303 (95%CI 1.588-3.340), 0.580 (95%CI
      0.343-0.978), and 0.183 (95%CI 0.091-0.368), respectively. A prognostic model for
      chronic HILI based on these four factors yielded the best prediction with a C
      statistic of 0.812 (95%CI 0.755-0.868), compared with MELD (C-statistic 0.506;
      95%CI 0.431-0.581) and Hy's law (C-statistic 0.418; 95%CI 0.343-0.492).
      CONCLUSION: Model for end-stage liver disease can be used to predict the fatal
      prognosis of HILI. A long latency, slow recovery, and low triglyceride value and
      platelet counts are important determinants for chronic HILI.

PMID- 30289392
TI  - Low molecular weight heparin treatment of acute moderate and severe pancreatitis:
      A randomized, controlled, open-label study.
AB  - BACKGROUND/AIMS: Acute pancreatitis (AP) runs a moderately severe and severe
      course in 20%-30% of cases. The purpose of the present study was to determine the
      effect of low molecular weight heparin (LMWH) for the prevention of pancreatic
      necrosis (PN) in moderately severe and severe AP (MSAP). MATERIALS AND METHODS: A
      total of 100 patients with MSAP were randomized to receive either standard care
      (SC) or SC plus LMWH. LMWH was administered at 1 mg/kg via subcutaneous injection
      twice a day between days 1 and 7. The revised Atlanta criteria were used in the
      diagnosis of MSAP. Patients with a Harmless AP Score of >=1 and a Balthazar
      computed tomography (CT) score of D and E were included in the study. RESULTS:
      The mean age+/-SD of the patients (46 male and 54 female) was 52+/-19 years
      (range, 17-100). There were 50 patients in each group. On admission, clinical and
      laboratory parameters and Balthazar CT scores were similar between the groups.
      Initially, PN was present in one patient in the LMWH group and two in the SC
      group. Over the course, PN developed in 3 (6.1%) patients in the LMWH group and
      11 (22.9%) in the SC group (p<0.05). Local and systemic complications were
      significantly lower in the LMWH group (p<0.05). No hemorrhagic complication
      occurred. Mortality was not significantly different between the groups (p=0.056).
      CONCLUSION: Low molecular weight heparin treatment is safe and provides better
      prognosis in MSAP.

PMID- 30289389
TI  - Multiple serine transposase dimers assemble the transposon-end synaptic complex
      during IS607-family transposition.
AB  - IS607-family transposons are unusual because they do not have terminal inverted
      repeats or generate target site duplications. They encode two protein-coding
      genes, but only tnpA is required for transposition. Our X-ray structures confirm
      that TnpA is a member of the serine recombinase (SR) family, but the chemically
      inactive quaternary structure of the dimer, along with the N-terminal location of
      the DNA binding domain, are different from other SRs. TnpA dimers from IS1535
      cooperatively associate with multiple subterminal repeats, which together with
      additional nonspecific binding, form a nucleoprotein filament on one transposon
      end that efficiently captures a second unbound end to generate the paired-end
      complex (PEC). Formation of the PEC does not require a change in the dimeric
      structure of the catalytic domain, but remodeling of the C-terminal alpha-helical
      region is involved. We posit that the PEC recruits a chemically-active conformer
      of TnpA to the transposon end to initiate DNA chemistry.

PMID- 30289393
TI  - Relationship between irritable bowel syndrome and plasma and tissue ghrelin
      levels.
AB  - BACKGROUND/AIMS: This study aimed to evaluate the relationship between irritable
      bowel syndrome (IBS) and plasma and tissue ghrelin levels. MATERIALS AND METHODS:
      Patients who had undergone gastroscopy procedure for any reason previously were
      enrolled in the study. Among these, patients with IBS symptoms were evaluated
      according to the Roma III criteria. The healthy control group comprised patients
      with no IBS symptom and had undergone gastroscopy procedure for another reason.
      The plasma ghrelin level and tissue ghrelin level obtained by immunohistochemical
      examination of biopsy specimens taken from the gastric antrum and corpus were
      evaluated in all participants. RESULTS: The mean age of 90 participants was
      43.64?}12.64 years. The median value of the plasma ghrelin level was 3.29 (1.2
      12.7) in the diarrhea group (IBS-D), 1.49 (0.82-7.08) in the constipation group
      (IBS-C), and 1.5 (0.2-3.7) in the control group. The plasma ghrelin levels
      between the groups were found to be significantly higher in IBS-D than in IBS-C
      and the control groups (p=0.001 and p=0.001, respectively). On comparing antral
      mucosal gland biopsy outcomes among the groups, staining intensity score was
      found to be significantly high in IBS-C as compared with the control group,
      whereas no significant difference was observed between IBS-D and the control
      groups (p=0.020 and p=0.429, respectively). CONCLUSION: The plasma ghrelin level
      in IBS-D and the staining intensity in the antral mucosal gland in IBS-C were
      found to be significantly higher. In addition, there was no difference between
      the groups in terms of ghrelin staining intensity in the gastric corpus.

PMID- 30289394
TI  - Positive effect of single nucleotide RAD51 135G>C polymorphism and low Ku70
      protein expression on female rectal cancer patients survival after preoperative
      radiotherapy.
AB  - BACKGROUND/AIMS: This is a retrospective analysis of 103 patients having locally
      advanced rectal cancer who received short-course radiotherapy (SCRT). The
      objective of the study was to check whether a polymorphism in the RAD51 gene (135
      G>C), Ku70 protein expression, and tumor microenvironment: proliferation rate
      measured by BrdUrdLI and Ki-67LI, hypoxia (glucose transporter-1 expression), P53
      protein expression, and DNA ploidy can influence DNA repair capacity, the factors
      contributing to patient overall survival (OS) and the incidence of recurrences
      and metastases. MATERIALS AND METHODS: RAD51 (135 G>C) polymorphism was evaluated
      using restriction fragment length polymorphism polymerase chain reaction, and
      proteins were identified using immunohistochemistry. RESULTS: There were 3 (2.9%)
      tumors with RAD51 CC, 75 (72.8%) with GG, and 25 (24.3%) with GC genotypes. The
      median follow-up time was 63.1 months (range 2-120). Patients with CC genotype
      survived significantly longer than those with GG and GC genotypes and did not
      develop any recurrences or distant metastases. Female patients with Ku70
      expression (<=75.1) or RAD51CC genotype (impaired DNA damage repair and
      radiosensitive) had significantly longer OS (p=0.013) than those with Ku70>75.1 %
      or RAD51GG,GC (radioresistant phenotype) and male patients in the log-rank test.
      In multivariate analysis, positive prognostic factors for OS in the male patients
      were grade=1 and <=17 days break in the treatment, whereas in the female
      subgroup, only radiosensitive phenotype (Ku70 <=75.1% or RAD51CC genotype).
      CONCLUSION: To the best of our knowledge, this is the first study to provide
      evidence for the positive effect of CC genotype of RAD51 or low Ku70 expression
      on OS in females with rectal cancer after SCRT.

PMID- 30289395
TI  - The evaluation of the effect of Helicobacter pylori infection on choroidal
      thickness.
AB  - BACKGROUND/AIMS: To evaluate the effects of Helicobacter pylori infection on
      choroidal thickness (CT) using enhanced depth imaging spectral domain-optical
      coherence tomography (SD-OCT). MATERIALS AND METHODS: A total of 63 right eyes of
      63 patients who tested positive for H. pylori (Group 1) and 46 right eyes of 46
      patients who tested negative for H. pylori (Group 2) were evaluated. The CTs at
      the subfoveal area and at 1 mm ranging up to 3 mm from the fovea at the nasal and
      temporal quadrants were measured and compared. After the eradication of H.
      pylori, the CT values were also compared with the pre-eradication values in 38
      patients. RESULTS: The mean age of patients was 43.6?}9.5 years in Group 1 and
      46.6?}11.5 years in Group 2 (p=0.13). Differences in CT values between Groups 1
      and 2 before and after H. pylori eradication were not statistically significant
      (p>0.05 for all values). CONCLUSION: The CT values of H. pylori positive and H.
      pylori negative patients were similar. Eradication of H. pylori infection appears
      to have produced no change in short-term CT.

PMID- 30289396
TI  - Molecular and presymptomatic analysis of a Moroccan Lynch syndrome family
      revealed a novel frameshift MLH1 germline mutation.
AB  - Lynch syndrome (LS) is an autosomal dominant disorder characterized by an
      increased risk of extracolonic cancers and early age of onset. It is associated
      with germline mutations in the DNA mismatch repair (MMR) genes. We report a case
      of a patient with colorectal cancer referred to our medical genetics department
      for molecular analysis and genetic counseling. The proband is a 64-year-old woman
      diagnosed with a tumor of the cecum. Histopathological examination showed a
      moderately differentiated mucinous adenocarcinoma categorized by pT3 N0. Analysis
      of her pedigree revealed three siblings who had colon cancer, as well as one
      relative with brain cancer. Based on these findings, molecular genetic
      investigation was found to be necessary in order to identify the disease-causing
      mutation. Immunohistochemistry staining of MMR proteins was performed on the
      tumor sample of the index proband. Mutational analysis of the MLH1/MSH2 genes was
      carried out. Analysis was extended to the family members and the general
      population. This led to the identification of a heterozygous frameshift
      duplication in the MLH1 gene at position 910 (c.910dupG). Three siblings had
      inherited the mutation from their mother, two of whom were asymptomatic at the
      time of diagnosis. To the best of our knowledge, this is a novel pathogenic
      duplication that has not been reported in the databases and literature. The
      outcome of the present case suggests that this mutation was the primary cause of
      LS in the family.

PMID- 30289397
TI  - Hypogammaglobulinemic sprue manifested as chronic intestinal failure: An uncommon
      but effective indication for home parenteral nutrition.

PMID- 30289398
TI  - Double pigtail stents healed acute pancreatitis resulting from afferent loop
      obstruction.

PMID- 30289399
TI  - A non-obstructive gastric antral web case detected after upper gastrointestinal
      system bleeding.

PMID- 30289400
TI  - Primary malignant melanoma of the esophagus.

PMID- 30289401
TI  - Appendiceal mucinous cystadenocarcinoma with mural nodules of anaplastic
      carcinoma and K-RAS mutation.

PMID- 30289402
TI  - Therapeutic plasma exchange for hypertriglyceridemia induced acut pancreatitis:
      the 33 cases experience from a tertiary reference center in Turkey.
AB  - BACKGROUND/AIMS: Hypertriglyceridemia (HTG) is the third most common cause of
      acute pancreatitis. In patients with severe HTG (TG level>1000 mg/dL), it may be
      beneficial to immediately lower the levels of triglyceride (TG) and chylomicrons.
      In this study, we present one of the largest case series on the use of
      therapeutic plasma exchange (TPE) for hypertriglyceridemia-induced acute
      pancreatitis (HTG-AP). MATERIALS AND METHODS: Overall, 33 patients who were
      admitted to our clinic for HTG-AP and underwent TPE between January 2007 and July
      2017 were included in the study. Clinical data and outcomes and the reduction of
      triglyceride levels were examined retrospectively. RESULTS: The TG level
      decreased by 54.4%, and the total cholesterol level decreased by 52.1% after one
      TPE session. The TG decrease after the second TPE session was found to be 79.4%.
      There were 20 (60.6%) patients with mild acute pancreatitis, 10 (30.3%) patients
      with moderetaly severe acute pancreatitis, and 3 (9.1%) patients with severe
      acute pancreatitis based on the categorization according to the revised Atlanta
      criteria. Regarding local complications, the acute peripancreatic fluid
      collection was observed in 13 (39.4%) patients, acute necrotic collection was
      observed in 1 (3%) patient, walled-off necrosis was observed in 1 (3%) patient,
      and pancreatic pseudocyst was not observed in any patient. Mortality was not
      determined in patients with mild and moderately severe acute pancreatitis, and
      its rate was 33.3% in patients with severe acute pancreatitis. The overall
      mortality rate was 3%. No significant complications related to TPE were noted.
      CONCLUSION: TPE is a safe and helpful therapeutic treatment method for patients
      with HTG-AP and may be considered particularly in patients with severe acute
      pancreatitis.

PMID- 30289403
TI  - Comment on "Changes in acute viral hepatitis epidemiology in the Turkish adult
      population: A multicenter study".

PMID- 30289404
TI  - Structure and function of a glycoside hydrolase family 8 endoxylanase from
      Teredinibacter turnerae.
AB  - The biological conversion of lignocellulosic matter into high-value chemicals or
      biofuels is of increasing industrial importance as the sector slowly transitions
      away from nonrenewable sources. Many industrial processes involve the use of
      cellulolytic enzyme cocktails - a selection of glycoside hydrolases and,
      increasingly, polysaccharide oxygenases - to break down recalcitrant plant
      polysaccharides. ORFs from the genome of Teredinibacter turnerae, a symbiont
      hosted within the gills of marine shipworms, were identified in order to search
      for enzymes with desirable traits. Here, a putative T. turnerae glycoside
      hydrolase from family 8, hereafter referred to as TtGH8, is analysed. The enzyme
      is shown to be active against beta-1,4-xylan and mixed-linkage (beta-1,3,beta
      1,4) marine xylan. Kinetic parameters, obtained using high-performance anion
      exchange chromatography with pulsed amperometric detection and 3,5
      dinitrosalicyclic acid reducing-sugar assays, show that TtGH8 catalyses the
      hydrolysis of beta-1,4-xylohexaose with a kcat/Km of 7.5 * 107 M-1 min-1 but
      displays maximal activity against mixed-linkage polymeric xylans, hinting at a
      primary role in the degradation of marine polysaccharides. The three-dimensional
      structure of TtGH8 was solved in uncomplexed and xylobiose-, xylotriose- and
      xylohexaose-bound forms at approximately 1.5 A resolution; the latter was
      consistent with the greater kcat/Km for hexasaccharide substrates. A 2,5B boat
      conformation observed in the -1 position of bound xylotriose is consistent with
      the proposed conformational itinerary for this class of enzyme. This work shows
      TtGH8 to be effective at the degradation of xylan-based substrates, notably
      marine xylan, further exemplifying the potential of T. turnerae for effective and
      diverse biomass degradation.

PMID- 30289407
TI  - Co-crystallization of human inositol monophosphatase with the lithium mimetic L
      690,330.
AB  - Lithium, which is still the gold standard in the treatment of bipolar disorder,
      has been proposed to inhibit inositol monophosphatase (IMPase) and is
      hypothesized to exert its therapeutic effects by attenuating phosphatidylinositol
      (PI) cell signalling. Drug-discovery efforts have focused on small-molecule
      lithium mimetics that would specifically inhibit IMPase without exhibiting the
      undesired side effects of lithium. L-690,330 is a potent bisphosphonate substrate
      based inhibitor developed by Merck Sharp & Dohme. To aid future structure-based
      inhibitor design, determination of the exact binding mechanism of L-690,330 to
      IMPase was of interest. Here, the high-resolution X-ray structure of human IMPase
      in complex with L690,330 and manganese ions determined at 1.39 A resolution is
      reported.

PMID- 30289406
TI  - Precipitant-ligand exchange technique reveals the ADP binding mode in
      Mycobacterium tuberculosis dethiobiotin synthetase.
AB  - Dethiobiotin synthetase from Mycobacterium tuberculosis (MtDTBS) is a promising
      antituberculosis drug target. Small-molecule inhibitors that target MtDTBS
      provide a route towards new therapeutics for the treatment of antibiotic
      resistant tuberculosis. Adenosine diphosphate (ADP) is an inhibitor of MtDTBS;
      however, structural studies into its mechanism of inhibition have been
      unsuccessful owing to competitive binding to the enzyme by crystallographic
      precipitants such as citrate and sulfate. Here, a crystallographic technique
      termed precipitant-ligand exchange has been developed to exchange protein-bound
      precipitants with ligands of interest. Proof of concept for the exchange method
      was demonstrated using cytidine triphosphate (CTP), which adopted the same
      binding mechanism as that obtained with traditional crystal-soaking techniques.
      Precipitant-ligand exchange also yielded the previously intractable structure of
      MtDTBS in complex with ADP solved to 2.4 A resolution. This result demonstrates
      the utility of precipitant-ligand exchange, which may be widely applicable to
      protein crystallography.

PMID- 30289405
TI  - Rational modification of vanillin derivatives to stereospecifically destabilize
      sickle hemoglobin polymer formation.
AB  - Increasing the affinity of hemoglobin for oxygen represents a feasible and
      promising therapeutic approach for sickle cell disease by mitigating the primary
      pathophysiological event, i.e. the hypoxia-induced polymerization of sickle
      hemoglobin (Hb S) and the concomitant erythrocyte sickling. Investigations on a
      novel synthetic antisickling agent, SAJ-310, with improved and sustained
      antisickling activity have previously been reported. To further enhance the
      biological effects of SAJ-310, a structure-based approach was employed to modify
      this compound to specifically inhibit Hb S polymer formation through interactions
      which perturb the Hb S polymer-stabilizing alphaF-helix, in addition to primarily
      increasing the oxygen affinity of hemoglobin. Three compounds, TD-7, TD-8 and TD
      9, were synthesized and studied for their interactions with hemoglobin at the
      atomic level, as well as their functional and antisickling activities in vitro. X
      ray crystallographic studies with liganded hemoglobin in complex with TD-7 showed
      the predicted mode of binding, although the interaction with the alphaF-helix was
      not as strong as expected. These findings provide important insights and guidance
      towards the development of molecules that would be expected to bind and make
      stronger interactions with the alphaF-helix, resulting in more efficacious novel
      therapeutics for sickle cell disease.

PMID- 30289408
TI  - Identification of the site of oxidase substrate binding in Scytalidium
      thermophilum catalase.
AB  - The catalase from Scytalidium thermophilum is a homotetramer containing a heme d
      in each active site. Although the enzyme has a classical monofunctional catalase
      fold, it also possesses oxidase activity towards a number of small organics,
      including catechol and phenol. In order to further investigate this, the crystal
      structure of the complex of the catalase with the classical catalase inhibitor 3
      amino-1,2,4-triazole (3TR) was determined at 1.95 A resolution. Surprisingly, no
      binding to the heme site was observed; instead, 3TR occupies a binding site
      corresponding to the NADPH-binding pocket in mammalian catalases at the entrance
      to a lateral channel leading to the heme. Kinetic analysis of site-directed
      mutants supports the assignment of this pocket as the binding site for oxidase
      substrates.

PMID- 30289410
TI  - Crystallography on a chip - without the chip: sheet-on-sheet sandwich.
AB  - Crystallography chips are fixed-target supports consisting of a film (for example
      Kapton) or wafer (for example silicon) that is processed using semiconductor
      microfabrication techniques to yield an array of wells or through-holes in which
      single microcrystals can be lodged for raster-scan probing. Although relatively
      expensive to fabricate, chips offer an efficient means of high-throughput sample
      presentation for serial diffraction data collection at synchrotron or X-ray free
      electron laser (XFEL) sources. Truly efficient loading of a chip (one
      microcrystal per well and no wastage during loading) is nonetheless challenging.
      The wells or holes must match the microcrystal size of interest, requiring that a
      large stock of chips be maintained. Raster scanning requires special mechanical
      drives to step the chip rapidly and with micrometre precision from well to well.
      Here, a 'chip-less' adaptation is described that essentially eliminates the
      challenges of loading and precision scanning, albeit with increased, yet still
      relatively frugal, sample usage. The device consists simply of two sheets of
      Mylar with the crystal solution sandwiched between them. This sheet-on-sheet
      (SOS) sandwich structure has been employed for serial femtosecond crystallography
      data collection with micrometre-sized crystals at an XFEL. The approach is also
      well suited to time-resolved pump-probe experiments, in particular for long time
      delays. The SOS sandwich enables measurements under XFEL beam conditions that
      would damage conventional chips, as documented here. The SOS sheets hermetically
      seal the sample, avoiding desiccation of the sample provided that the X-ray beam
      does not puncture the sheets. This is the case with a synchrotron beam but not
      with an XFEL beam. In the latter case, desiccation, setting radially outwards
      from each punched hole, sets lower limits on the speed and line spacing of the
      raster scan. It is shown that these constraints are easily accommodated.

PMID- 30289409
TI  - Using sound pulses to solve the crystal-harvesting bottleneck.
AB  - Crystal harvesting has proven to be difficult to automate and remains the rate
      limiting step for many structure-determination and high-throughput screening
      projects. This has resulted in crystals being prepared more rapidly than they can
      be harvested for X-ray data collection. Fourth-generation synchrotrons will
      support extraordinarily rapid rates of data acquisition, putting further pressure
      on the crystal-harvesting bottleneck. Here, a simple solution is reported in
      which crystals can be acoustically harvested from slightly modified MiTeGen In
      Situ-1 crystallization plates. This technique uses an acoustic pulse to eject
      each crystal out of its crystallization well, through a short air column and onto
      a micro-mesh (improving on previous work, which required separately grown
      crystals to be transferred before harvesting). Crystals can be individually
      harvested or can be serially combined with a chemical library such as a fragment
      library.

PMID- 30289413
TI  - Structural insights into the recognition of phosphorylated Hop1 by Mek1.
AB  - The FHA domain-containing protein Mek1 is a meiosis-specific kinase that is
      involved in the regulation of interhomolog recombination in meiosis in
      Saccharomyces cerevisiae. The recruitment and activation of Mek1 require the
      phosphorylation of the chromosome axis protein Hop1 at Thr318 (pT318), which is
      necessary for recognition by the Mek1 FHA domain. Here, crystal structures of the
      Mek1 FHA domain in the apo state and in complex with the Hop1 pT318 peptide are
      presented, demonstrating that the hydrophobic residues Phe320 and Val321 at the
      pT+2 and pT+3 positions in the ligand contribute to the preferential recognition.
      It was further found that in Schizosaccharomyces pombe Mek1 FHA binds both pT15
      in its N-terminal SQ/TQ cluster domain (SCD) and pT270 in the Hop1 SCD. The
      results revealed the structural basis for the preferential recognition of
      phosphorylated Hop1 by Mek1 in S. cerevisiae and facilitate the understanding of
      the interaction between the S. pombe Mek1 FHA domain and its binding targets.

PMID- 30289411
TI  - The X-ray structure of human calbindin-D28K: an improved model.
AB  - Calbindin-D28K is a widely expressed calcium-buffering cytoplasmic protein that
      is involved in many physiological processes. It has been shown to interact with
      other proteins, suggesting a role as a calcium sensor. Many of the targets of
      calbindin-D28K are of therapeutic interest: for example, inositol
      monophosphatase, the putative target of lithium therapy in bipolar disorder.
      Presented here is the first crystal structure of human calbindin-D28K. There are
      significant deviations in the tertiary structure when compared with the NMR
      structure of rat calbindin-D28K (PDB entry 2g9b), despite 98% sequence identity.
      Small-angle X-ray scattering (SAXS) indicates that the crystal structure better
      predicts the properties of calbindin-D28K in solution compared with the NMR
      structure. Here, the first direct visualization of the calcium-binding properties
      of calbindin-D28K is presented. Four of the six EF-hands that make up the
      secondary structure of the protein contain a calcium-binding site. Two distinct
      conformations of the N-terminal EF-hand calcium-binding site were identified
      using long-wavelength calcium single-wavelength anomalous dispersion (SAD). This
      flexible region has previously been recognized as a protein-protein interaction
      interface. SAXS data collected in both the presence and absence of calcium
      indicate that there are no large structural differences in the globular structure
      of calbindin-D28K between the calcium-loaded and unloaded proteins.

PMID- 30289412
TI  - High-resolution crystal structures of the D1 and D2 domains of protein tyrosine
      phosphatase epsilon for structure-based drug design.
AB  - Here, new crystal structures are presented of the isolated membrane-proximal D1
      and distal D2 domains of protein tyrosine phosphatase epsilon (PTPE), a protein
      tyrosine phosphatase that has been shown to play a positive role in the survival
      of human breast cancer cells. A triple mutant of the PTPE D2 domain
      (A455N/V457Y/E597D) was also constructed to reconstitute the residues of the PTPE
      D1 catalytic domain that are important for phosphatase activity, resulting in
      only a slight increase in the phosphatase activity compared with the native D2
      protein. The structures reported here are of sufficient resolution for structure
      based drug design, and a microarray-based assay for high-throughput screening to
      identify small-molecule inhibitors of the PTPE D1 domain is also described.

PMID- 30289414
TI  - Remoulding a MOF's pores by auxiliary ligand introduction for stability
      improvement and highly selective CO2-capture.
AB  - A new highly porous mixed-valence metal-organic framework, Co-pydc, was
      synthesized and characterized. Upon guest loss, Co-pydc irreversibly transformed
      to a closed structure and lost pore functionality. Then an auxiliary ligand was
      introduced as a girder to support the framework in the synthesis process, and
      successfully afforded a new porous MOF, Co-pydc-TPB. This displays a considerably
      enhanced robust framework which is resistant to guest loss and stable up to 400 
      degrees C, retains single-crystallinity at 300  degrees C, shows good water and
      alkali resistance, and selective adsorption of CO2 over N2 at room temperature.

PMID- 30289415
TI  - Application of electrochemical surface plasmon resonance (ESPR) to the study of
      electroactive microbial biofilms.
AB  - Electrochemical surface plasmon resonance (ESPR) monitors faradaic processes
      optically by the change in refractive index that occurs with a change in redox
      state at the electrode surface. Here we apply ESPR to investigate the anode-grown
      Geobacter sulfurreducens biofilm (GSB), a model system used to study
      electroactive microbial biofilms (EABFs) which perform electrochemical reactions
      using electrodes as metabolic electron acceptors or donors. A substantial body of
      evidence indicates that electron transfer reactions among hemes of c-type
      cytochromes (c-Cyt) play major roles in the extracellular electron transfer (EET)
      pathways that connect intracellular metabolic processes of cells in an EABF to
      the electrode surface. The results reported here reveal that when the potential
      of the electrode is changed from relatively oxidizing (0.40 V vs. SHE) to
      reducing (-0.55 V vs. SHE) and then back to oxidizing, 70% of c-Cyt residing
      closest to the biofilm/electrode (within hundreds of nm from the electrode
      surface) appear to remain trapped in the reduced state, requiring as long as 12
      hours to be re-oxidized. c-Cyt storing electrons cannot contribute to EET, yet
      turnover current resulting from cellular oxidation of acetate coupled with EET to
      the electrode surface is unaffected. This suggests that a relatively small
      fraction of c-Cyt residing closest to the biofilm/electrode interface is involved
      in EET while the majority store electrons. The results also reveal that biomass
      density at the biofilm/electrode interface increases rapidly during lag phase,
      reaching its maximum value at the onset of exponential biofilm growth when
      turnover current begins to rapidly increase.

PMID- 30289416
TI  - Copper-catalyzed propargylic [3+3] cycloaddition with 1H-pyrazol-5(4H)-ones:
      enantioselective access to optically active dihydropyrano[2,3-c]pyrazoles.
AB  - A copper-catalyzed asymmetric propargylic [3+3] cycloaddition with 1H-pyrazol
      5(4H)-ones as C,O-bisnucleophiles through the desilylation-activated strategy has
      been developed. With the catalysis of Cu(OAc)2.H2O in combination with a chiral
      tridentate P,N,N-ligand, the reaction displayed a broad substrate scope, and thus
      provided a variety of chiral dihydropyrano[2,3-c]pyrazoles in high yields and
      with excellent enantioselectivities (up to 96% ee).

PMID- 30289417
TI  - Bubble-bubble pinch-off in symmetric and asymmetric microfluidic expansion
      channels for ordered foam generation.
AB  - By incorporating the techniques of geometrically mediated splitting and bubble
      bubble breakup, the present work offers a novel microfluidic foam generation
      system via production of segregated, mono- or bidisperse bubbles at capacities
      exceeding 10 000 bubbles per second. Bubble-bubble pinch-off is precise at high
      capillary numbers (Ca > 0.065), generating monodisperse or bidisperse daughter
      bubbles for a symmetric or an asymmetric expansion respectively. Bi- or
      tridisperse foam is produced as pinch-off perfectly alternates such that the
      system contains twice the number of fragmented bubbles as intact bubbles. A
      relationship between the upstream bubble extension and the capillary number
      demarcates the different regimes of pinch-off defined with respect to frequency
      and precision: non-splitting, irregular, polydisperse, and monodisperse (or
      bidisperse for an asymmetric expansion). For tridisperse foam generation via a
      fixed asymmetric expansion geometry, the wall bubble confinement can be tuned to
      adjust the pinch-off accuracy in order to access a spectrum of fragmented bubble
      size ratios. The simplicity in operating and characterizing our system will
      enable studies on dynamic bubble interactions and ordered, wet foam applications.

PMID- 30289418
TI  - Large amplitude motion within acetylene-rare gas complexes hosted in helium
      droplets.
AB  - Near-infrared spectroscopy of the C2H2-Ar, Kr complexes was performed in the
      spectral region overlapping the nu3/nu2 + nu4 + nu5 Fermi-type resonance of C2H2.
      The experiment was conducted along the HElium NanoDroplet Isolation (HENDI)
      technique in order to study the coupling dynamics between a floppy molecular
      system (C2H2-Ar and C2H2-Kr) and a mesoscopic quantum liquid (the droplet).
      Calculations were performed using a spectral element based close-coupling program
      and state-of-the-art 2-dimensional potential energy surfaces to determine the
      bound states of the C2H2-Ar and C2H2-Kr complexes and simulate the observed
      spectra. This furnished a quantitative basis to unravel how the superfluid and
      non-superfluid components of the droplet affect the rotation and the deformation
      dynamics of the hosted complex.

PMID- 30289419
TI  - Photo-induced free radical production in a tetraphenylethylene ligand-based metal
      organic framework.
AB  - Photo-induced free radical production was observed in tetraphenylethylene ligand
      based metal-organic frameworks (MOFs). This feature endows the MOFs with
      reversible, fast, obvious, and controllable photo-induced color/emission
      transformation, excellent fatigue resistance ability and good light stability.

PMID- 30289420
TI  - Probing the band gap of liquid ammonia with femtosecond multiphoton ionization
      spectroscopy.
AB  - The electronic band gap, i.e. the energy difference between the top of the
      valence band and the bottom of the conduction band, is widely recognized as the
      key property characterizing the electronic structure of bulk liquids and liquid
      solvents like water or ammonia. Here, the band gap of liquid ammonia at 270 K and
      300 bar was studied with 2-photon ionization spectroscopy using the solvated
      electron primary yield as a near-infrared action-spectroscopic probe. The
      experimentally determined escape probability, which is the fraction of solvated
      electrons that is able to avoid geminate recombination within the first
      nanosecond after ionization, was used to extract a value of -(1.27 +/- 0.03) eV
      for the vertical electron affinity of the liquid.

PMID- 30289421
TI  - Ultrafast unidirectional chiral rotation in the Z-E photoisomerization of two
      azoheteroarene photoswitches.
AB  - Unidirectional rotation represents a very important functional feature in
      photochemistry, such as in the design of light-driven molecular rotary motors.
      Great attention has recently been devoted to the unidirectional preference of the
      torsional motion of azobenzene and other molecules. Azoheteroarenes offer
      functional advantages over their more conventional azobenzene counterparts due to
      the introduction of heteroaromatic rings. In this paper, the Z-E
      photoisomerization dynamics of two azoheteroarenes, 1,2-bis(1-methyl-1H-imidazol
      2-yl)diazene and 1,2-bis(1H-imidazol-2-yl)diazene, are investigated with
      trajectory surface-hopping molecular dynamics at the semi-empirical OM2/MRCI
      level. Starting from the S1 excited state of the M-helical Z-isomer of both
      azoheteroarenes, more than 99% of the trajectories decay to their ground states
      through the M-helical conical intersections by twisting about the central
      N[double bond, length as m-dash]N double bond. This chiral path preference can be
      well understood by the energy profiles generated by the linear interpolation
      between the Franck-Condon geometry of the M-helical Z-isomer and the relevant
      S1/S0 conical intersections. The Z-E photoisomerization mechanisms of these two
      azoheteroarenes display a higher preference for unidirectional rotary dynamics
      under a chiral path than their counterpart azobenzene.

PMID- 30289422
TI  - Qualitative analysis of antibody-drug conjugates (ADCs): an experimental
      comparison of analytical techniques of cysteine-linked ADCs.
AB  - Antibody-drug conjugates (ADCs) are an emerging type of biotherapeutics that
      utilize multiple tissue-specific antibodies combined with a range of linker
      designs to enable the transportation and selective release of cytotoxic drugs in
      close proximity to tumours. Consisting of antibodies conjugated to small drug
      molecules through a variety of linkers, ADCs are chemically complex analytes.
      Here we present a unique experimental comparison of four techniques for ADC
      analysis: hydrophobic interaction chromatography (HIC-UV/Vis), reversed phase
      liquid chromatography mass spectrometry (RPLC-MS), using either a QToF or an
      Orbitrap analyser, and matrix-assisted laser desorption ionization time-of-flight
      mass spectrometry (MALDI-TOF-MS). Four different ADCs consisting of Trastuzumab,
      monomethyl auristatin E (MMAE) and a peptidic linker moiety differing in their
      respective stoichiometric ratios in regard to drug-to-antibody ratio (DAR) were
      used for the comparison. We found that the determined DAR from all techniques was
      comparable, while the accuracy of the molecular weights for the conjugated light
      and heavy chain differed more extensively. This indicates that the choice of a
      mass analyser is more crucial for determining the accurate weights of the light
      and heavy chains than to evaluate the DAR of a given batch. However, ambiguous
      DAR assignment in HIC-UV/Vis or bias for either the light or heavy chain
      fragments in the mass spectrometry-based techniques can influence the obtained
      average DAR value and the use of complementary techniques is advisable. Out of
      the four techniques evaluated, HIC-UV/Vis and MALDI required less time to obtain
      an average DAR value and would therefore be good for initial screenings in the
      early stages of the discovery phase of new ADCs.

PMID- 30289423
TI  - Axially perpendicular offset scheme for obtaining Raman spectra of housed samples
      in glass bottles with minimized glass-peak background.
AB  - An axially perpendicular offset (APO) scheme based on an axially perpendicular
      geometrical arrangement of laser illumination and photon detection, enabling
      spatially offset Raman spectroscopy (SORS), is proposed as a versatile tool for
      the minimization of the glass background in direct measurements of Raman spectra
      of samples housed in glass bottles. This strategy is based on the possibility of
      isolating glass photons from sample photons by properly locating a detector
      beneath the sample-housing bottle, because glass photons are much more localized
      near the glass wall while sample photons are widely distributed throughout the
      bottle. In addition, the curved bottom of the glass vial enabling forming the
      conical photon-detection volume would be further effective in exclusion of the
      glass photons in the acquisition of sample spectra. The APO scheme was validated
      by measuring the Raman spectra of 66% ethanol housed in four glass bottles of
      different sizes and colors; the measurements were performed by varying the offset
      distance from 2 mm to 20 mm. The intensity of the glass background decreased
      rapidly with increasing the offset distance; on the other hand, the variation in
      the ethanol intensity was relatively insignificant. In all cases, the offset
      distance of 16 mm minimized the presence of glass background in the spectra,
      thereby helping to highlight the pure ethanol bands and producing nearly similar
      sample spectral features regardless of contained bottles. The results of the
      Monte Carlo simulation were in accordance with the experimental observations, and
      the suppression of glass photons in the APO scheme was clearly explained and
      visualized by the simulation.

PMID- 30289424
TI  - Ethanol, O, and CO adsorption on Pt nanoparticles: effects of nanoparticle size
      and graphene support.
AB  - Pt nanoparticles dispersed over carbonaceous supports are widely used as
      catalysts for different applications, making studies on the interplay between
      size and support effects indispensable for rational catalyst design. Here, we use
      DFT calculations to simulate the interaction between O, CO, and ethanol with free
      platinum cuboctahedral nanoparticles with up to 147 atoms and with the same Pt
      nanoparticles supported on a single layer of graphene with up to 720 carbon
      atoms. We compute adsorption energies for each adsorbate on different adsorption
      sites for supported and unsupported Pt nanoparticles. We show that as the Pt
      nanoparticle grows the adsorption energy decreases, and that the size effect is
      more important for O and CO adsorption than for ethanol. We observe that the
      generalized coordination number of each adsorption site controls the interaction
      strength for O and CO to a much larger extent than for ethanol. Electronic charge
      redistributions and density of states projected on the d band of the interacting
      Pt facets are used to obtain a better understanding of the differences between
      the electronic interactions for each adsorbate. For Pt nanoparticles supported on
      graphene, the support effects weaken the adsorption energies for all the
      adsorbates, but this effect rapidly decreases with larger nanoparticles, and it
      is only significant for our smallest nanoparticle Pt13. By demonstrating that the
      effects of nanoparticle size and support are different for ethanol as compared
      with O and CO, we conclude that it should be possible to modify different
      parameters in the catalyst design in order to tune the Pt nanoparticle to
      interact with specific adsorbates.

PMID- 30289425
TI  - A randomized controlled trial of the impact of protein supplementation on leg
      lean mass and integrated muscle protein synthesis during inactivity and energy
      restriction in older persons.
AB  - Background: In older persons, muscle loss is accelerated during physical
      inactivity and hypoenergetic states, both of which are features of
      hospitalization. Protein supplementation may represent a strategy to offset the
      loss of muscle during inactivity, and enhance recovery on resumption of activity.
      Objective: We aimed to determine if protein supplementation, with proteins of
      substantially different quality, would alleviate the loss of lean mass by
      augmenting muscle protein synthesis (MPS) while inactive during a hypoenergetic
      state. Design: Participants (16 men, mean +/- SD age: 69 +/- 3 y; 15 women, mean
      +/- SD age: 68 +/- 4 y) consumed a diet containing 1.6 g protein . kg-1 . d-1,
      with 55% +/- 9% of protein from foods and 45% +/- 9% from supplements, namely,
      whey protein (WP) or collagen peptides (CP): 30 g each, consumed 2 times/d.
      Participants were in energy balance (EB) for 1 wk, then began a period of energy
      restriction (ER; -500 kcal/d) for 1 wk, followed by ER with step reduction (ER +
      SR; <750 steps/d) for 2 wk, before a return to habitual activity in recovery (RC)
      for 1 wk. Results: There were significant reductions in leg lean mass (LLM) from
      EB to ER, and from ER to ER + SR in both groups (P < 0.001) with no differences
      between WP and CP or when comparing the change from phase to phase. During RC,
      LLM increased from ER + SR, but in the WP group only. Rates of integrated muscle
      protein synthesis decreased during ER and ER + SR in both groups (P < 0.01), but
      increased during RC only in the WP group (P = 0.05). Conclusions: Protein
      supplementation did not confer a benefit in protecting LLM, but only supplemental
      WP augmented LLM and muscle protein synthesis during recovery from inactivity and
      a hypoenergetic state. This trial was registered at http://www.clinicaltrials.gov
      as NCT03285737.

PMID- 30289427
TI  - Bcl-3 promotes proliferation and chemosensitivity in BL1 subtype of TNBC cells.
AB  - Bcl-3 is an established oncogene in diverse malignant tumors. In this study, we
      investigated a dual role of Bcl-3 in BL1-subtype triple-negative breast cancer
      (TNBC). The BL1-subtype TNBC is featured by increasing cell cycle gene expression
      and the highest sensitivity to chemotherapy among all subtypes. Bcl-3 is
      associated with a better prognosis in BL1 patients. Bcl-3 knockdown in BL1 cell
      MDA-MB-468 induces the inhibition of cell proliferation and the G1/S transition
      arrest by promoting p27 and reducing the expressions of c-Myc and skp2 at mRNA
      and protein levels. Meanwhile, Bcl-3 enhances the sensitivity of MDA-MB-468 to
      chemotherapeutics ABX and PTX. Furthermore, the regulation mechanisms are
      restricted to BL1 cell and do not occur in SUM159PT, a typical MSL subtype of
      TNBC cell. These data suggest that Bcl-3 may be a potential clinical biomarker
      for diagnosis, treatment, and prognosis of patients with BL1-subtype TNBC.

PMID- 30289426
TI  - The Association of Changes in Pain Acceptance and Headache-Related Disability.
AB  - Background: Migraine accounts for substantial suffering and disability. Previous
      studies show cross-sectional associations between higher pain acceptance and
      lower headache-related disability in individuals with migraine, but none has
      evaluated this association longitudinally during migraine treatment. Purpose:
      This study evaluated whether changes in pain acceptance were associated with
      changes in headache-related disability and migraine characteristics in a
      randomized controlled trial (Women's Health and Migraine) that compared effects
      of behavioral weight loss (BWL) treatment and migraine education (ME) on headache
      frequency in women with migraine and overweight/obesity. Methods: This was a post
      hoc analysis of 110 adult women with comorbid migraine and overweight/obesity who
      received 16 weeks of either BWL or ME. Linear and nonlinear mixed effects
      modeling methods were used to test for between-group differences in change in
      pain acceptance, and also to examine the association between change in pain
      acceptance and change in headache disability. Results: BWL and ME did not differ
      on improvement in pain acceptance from baseline across post-treatment and follow
      up. Improvement in pain acceptance was associated with reduced headache
      disability, even when controlling for intervention-related improvements in
      migraine frequency, headache duration, and pain intensity. Conclusions: This
      study is the first to show that improvements in pain acceptance following two
      different treatments are associated with greater reductions in headache-related
      disability, suggesting a potential new target for intervention development.
      Clinical Trials information: NCT01197196.

PMID- 30289428
TI  - Reply to AL Buchman.

PMID- 30289429
TI  - Genetic inhibition of flowering differs between juvenile and adult Citrus trees.
AB  - Background and Aims: In woody species, the juvenile period maintains the axillary
      meristems in a vegetative stage, unable to flower, for several years. However, in
      adult trees, some 1-year-old meristems flower whereas others remain vegetative to
      ensure a polycarpic growth habit. Both types of trees, therefore, have non
      flowering meristems, and we hypothesize that the molecular mechanism regulating
      flower inhibition in juvenile trees is different from that in adult trees.
      Methods: In adult Citrus trees, the main endogenous factor inhibiting flower
      induction is the growing fruit. Thus, we studied the expression of the main
      flowering time, identity and patterning genes of trees with heavy fruit load (not
      flowering adult trees) compared to that of 6-month-old trees (not-flowering
      juvenile trees). Adult trees without fruits (flowering trees) were used as a
      control. Second, we studied the expression of the same genes in the meristems of
      6-month, and 1-, 3-, 5- and 7-year-old juvenile trees compared to 10-year-old
      flowering trees. Key Results: The axillary meristems of juvenile trees are unable
      to transcribe flowering time and patterning genes during the period of induction,
      although they are able to transcribe the FLOWERING LOCUS T citrus orthologue
      (CiFT2) in leaves. By contrast, meristems of not-flowering adult trees are able
      to transcribe the flowering network genes but fail to achieve the transcription
      threshold required to flower, due to CiFT2 repression by the fruit. Juvenile
      meristems progressively achieve gene expression, with age-dependent differences
      from 6 months to 7 years, FD-like and CsLFY being the last genes to be expressed.
      Conclusions: During the juvenile period the mechanism inhibiting flowering is
      determined in the immature bud, so that it progressively acquires flowering
      ability at the gene expression level of the flowering time programme, whereas in
      the adult tree it is determined in the leaf, where repression of CiFT2 gene
      expression occurs.

PMID- 30289430
TI  - Sexual dimorphism and rapid turnover in gene expression in pre-reproductive
      seedlings of a dioecious herb.
AB  - Background and Aims: Sexual dimorphism in morphology, physiology or life history
      traits is common in dioecious plants at reproductive maturity, but it is
      typically inconspicuous or absent in juveniles. Although plants of different
      sexes probably begin to diverge in gene expression both before their reproduction
      commences and before dimorphism becomes readily apparent, to our knowledge
      transcriptome-wide differential gene expression has yet to be demonstrated for
      any angiosperm species. Methods: The present study documents differences in gene
      expression in both above- and below-ground tissues of early pre-reproductive
      individuals of the wind-pollinated dioecious annual herb, Mercurialis annua,
      which otherwise shows clear sexual dimorphism only at the adult stage. Key
      Results: Whereas males and females differed in their gene expression at the first
      leaf stage, sex-biased gene expression peaked just prior to, and after,
      flowering, as might be expected if sexual dimorphism is partly a response to
      differential costs of reproduction. Sex-biased genes were over-represented among
      putative sex-linked genes in M. annua but showed no evidence for more rapid
      evolution than unbiased genes. Conclusions: Sex-biased gene expression in M.
      annua occurs as early as the first whorl of leaves is produced, is highly dynamic
      during plant development and varies substantially between vegetative tissues.

PMID- 30289431
TI  - Response to Associations Among Sodium Intake, Endothelial Dysfunction, and
      Endothelial Damage Biomarkers in Hypertension (AJH-D-18-00331).

PMID- 30289432
TI  - The Clinical Significance and Application of Vascular Stiffness Measurements.
AB  - Increasing evidence points out at vascular stiffness (and in particular aortic
      stiffness measured by pulse wave velocity) as a reliable biomarker of vascular
      aging, able to integrate in a single measure the overall burden of cardiovascular
      (CV) risk factors on the vasculature over time; furthermore, it may be per se a
      mechanism of disease, by inducing microcirculatory damage and favoring CV events.
      Increased aortic stiffness has been shown to predict future CV events and improve
      risk reclassification in those at intermediate risk. However, several questions
      in this field are still open, limiting the wide use of these tools in the
      clinical practice. This article will review the basic aspects of physiology of
      large artery stiffness, as well as current evidence about its possible clinical
      applications.

PMID- 30289434
TI  - Modeling liver cancer and therapy responsiveness using organoids derived from
      primary mouse liver tumors.
AB  - The current understanding of cancer biology and development of effective
      treatments for cancer remain far from satisfactory. This in turn heavily relies
      on the availability of easy and robust model systems that resemble the
      architecture/physiology of the tumors in patients to facilitate research. Cancer
      research in vitro has mainly been based on the use of immortalized 2D cancer cell
      lines that deviate in many aspects from the original primary tumors. The recent
      development of the organoid technology allowing generation of organ-buds in 3D
      culture from adult stem cells has endowed the possibility of establishing stable
      culture from primary tumors. Although culturing organoids from liver tumors is
      thought to be difficult, we now convincingly demonstrate the establishment of
      organoids from mouse primary liver tumors. We have succeeded in culturing 91
      lines from 129 liver tissue/tumors. These organoids can be grown in long-term
      cultures in vitro. About 20% of these organoids form tumors in immunodeficient
      mice upon (serial) transplantation, confirming their tumorigenic and self-renewal
      properties. Interestingly, single cells from the tumor organoids have high
      efficiency of organoid initiation, and a single organoid derived from a cancer
      cell is able to initiate a tumor in mice, indicating the enrichment of tumor
      initiating cells in the tumor organoids. Furthermore, these organoids
      recapitulate, to some extent, the heterogeneity of liver cancer in patients, with
      respect to phenotype, cancer cell composition and treatment response. These model
      systems shall provide enormous opportunities to advance our research on liver
      cancer (stem cell) biology, drug development and personalized medicine.

PMID- 30289433
TI  - Recommendation-based dietary indexes and risk of colorectal cancer in the Nurses'
      Health Study and Health Professionals Follow-up Study.
AB  - Background: Many dietary indexes exist for chronic disease prevention, but the
      optimal dietary pattern for colorectal cancer prevention is unknown. Objective:
      We sought to determine associations between adherence to various dietary indexes
      and incident colorectal cancer in 2 prospective cohort studies. Design: We
      followed 78,012 women in the Nurses' Health Study and 46,695 men in the Health
      Professionals Follow-up Study from 1986 and 1988, respectively, until 2012. We
      created dietary index scores for the Dietary Approaches to Stop Hypertension
      (DASH) diet, Alternative Mediterranean Diet (AMED), and Alternative Healthy
      Eating Index-2010 (AHEI-2010) and used Cox regression to estimate HRs and 95% CIs
      for risk of colorectal cancer (CRC) and by anatomic subsite. We also conducted
      latency analyses to examine associations between diet and CRC risk during
      different windows of exposure. We conducted analyses in men and women separately,
      and subsequently pooled these results in a random-effects meta-analysis. Results:
      We documented 2690 colorectal cancer cases. Pooled multivariable HRs for
      colorectal cancer risk comparing the highest to lowest quintile of diet scores
      were 0.89 (95% CI: 0.74, 1.08; P-trend = 0.10) for DASH, 0.89 (95% CI: 0.73,
      1.10; P-trend = 0.31) for AMED, and 0.95 (95% CI: 0.83, 1.09; P-trend = 0.56) for
      AHEI-2010 (P-heterogeneity >= 0.07 for all). In sex-specific analyses, we
      observed stronger associations in men for all dietary indexes (DASH:
      multivariable HR = 0.81, 95% CI: 0.66, 0.98; P-trend = 0.003; AMED: multivariable
      HR = 0.80, 95% CI: 0.65, 0.98; P-trend = 0.02; AHEI-2010: multivariable HR =
      0.88, 95% CI: 0.72, 1.07; P-trend = 0.04) than in women (multivariable HRs range
      from 0.98 to 1.01). Conclusions: Adherence to the DASH, AMED, and AHEI-2010 diets
      was inversely associated with colorectal cancer risk in men. These diets were not
      associated with colorectal cancer risk in women. This observational study was
      registered at http://www.clinicaltrials.gov as NCT03364582.

PMID- 30289436
TI  - The Golden Ratio and Aesthetic Surgery.

PMID- 30289435
TI  - Phase 1 Safety and Pharmacokinetics Study of MK-2048/Vicriviroc (MK-4176)/MK
      2048A Intravaginal Rings.
AB  - Background: Vaginal rings (VR) containing antiretroviral (ARV) drugs can be
      utilized for prevention of human immunodeficiency virus (HIV) with potential for
      improved adherence compared to daily pills. Combination ARV VRs could improve
      efficacy. Methods: MTN-027, a single-blind, randomized, placebo-controlled trial
      in 48 women, evaluated VRs containing MK-2048 (30 mg) and vicriviroc (VCV, 182
      mg), alone or in combination, and placebo used continuously for 28 days. Safety
      was assessed by recording adverse events. Drug concentrations were quantified in
      plasma, vaginal fluid, cervical tissue, and rectal fluid. Cervical tissue was
      utilized for ex vivo HIV inhibition analysis. Results: There was no difference in
      related genitourinary adverse events between treatment arms compared to placebo.
      VCV and MK-2048 released from single or combination VRs both achieved peak
      concentrations in vaginal fluids, which were substantially higher compared to
      plasma (200* for VCV, 30* for MK-2048) and rectal fluid. In an ex vivo challenge
      assay, the antiviral activity of VCV and/or MK-2048 was not correlated with
      tissue-associated drug concentrations. Most women (77%) were fully adherent to 28
      days of continuous VR use and found the VR acceptable. Conclusions: VCV and/or MK
      2048 containing VRs were safe and acceptable. Both VCV and MK-2048 were
      quantifiable in all matrixes tested with peak compartmental drug concentrations
      similar for single and combination drug VRs. Tissue-associated VCV and/or MK-2048
      did not correlate with inhibition of HIV infection. These data highlight the need
      to assess adequacy of drug dosing in the VR and measuring genital tissue drug
      concentrations to develop more precise concentration-response relationships.

PMID- 30289437
TI  - CIRCOAST: a statistical hypothesis test for cellular colocalization with network
      structures.

PMID- 30289438
TI  - Effect of food predictability on lifespan in male mice.
AB  - The purpose of this study is to compare the effect of unpredictable (U) or
      predictable (P) food delivery on health and longevity in mice. From 2 months of
      age until end of life, singly-housed male C57BL/6 mice were fed a semisynthetic
      diet either ad libitum (AL), or as imposed meals delivered as small pellets at
      either P or U times, frequencies, or amounts. The total daily food consumed by
      all groups was the same. The AL group gained body weight faster than either P or
      U groups, and had ~12% shorter median life span compared with either P or U
      groups. Bimonthly non-invasive body composition determinations showed that the
      differences in body weights were due to differences in fat and lean mass. Post
      mortem examinations revealed that the organ pathologies were similar in all
      groups, but a larger fraction of P and U mice were euthanized due to end-of-life
      suffering. There were no systematic differences in outcome measures between P and
      U groups suggesting that, within the range studied, the temporal pattern of food
      delivery did not have a significant metabolic effect.

PMID- 30289439
TI  - XY oocytes of sex-reversed females with a Sry mutation deviate from the normal
      developmental process beyond the mitotic stage.
AB  - The fertility of sex-reversed XY female mice is severely impaired by a massive
      loss of oocytes and failure of meiotic progression. This phenomenon remains an
      outstanding mystery. We sought to determine the molecular etiology of XY oocyte
      dysfunction by generating sex-reversed females that bear genetic ablation of Sry,
      a vital sex determination gene, on an inbred C57BL/6 background. These mutant
      mice, termed XYsry- mutants, showed severe attrition of germ cells during fetal
      development, resulting in the depletion of ovarian germ cells prior to sexual
      maturation. Comprehensive transcriptome analyses of primordial germ cells and
      postnatal oocytes demonstrated that XYsry- females had deviated significantly
      from normal developmental processes during the stages of mitotic proliferation.
      The impaired proliferation of XYsry- PGCs was associated with aberrant beta
      catenin signaling and the excessive expression of transposable elements. Upon
      entry to the meiotic stage, XYsry- oocytes demonstrated extensive defects,
      including the impairment of crossover formation, the failure of primordial
      follicle maintenance, and no capacity for embryo development. Together, these
      results suggest potential molecular causes for germ cell disruption in sex
      reversed female mice, thereby providing insights into disorders of sex
      differentiation in humans, such as "Swyer syndrome," in which patients with an XY
      karyotype present as typical females and are infertile.

PMID- 30289440
TI  - Mesenchymal Stem Cells for Periodontal Tissue Regeneration in Elderly Patients.
AB  - Mesenchymal stem cell (MSC) grafting is a highly promising alternative strategy
      for periodontal regeneration in periodontitis, which is one of the primary causes
      of tooth loss in the elderly. However, aging progressively decreases the
      proliferative and differentiation potential of MSCs and diminishes their
      regenerative capacity, which represents a limiting factor for their endogenous
      use in elderly patients. Therefore, tissue regeneration therapy with MSCs in this
      age group may require a cellular source without the physiological limitations
      that MSCs exhibit in aging. In this sense, exogenous or allogeneic MSCs could
      have a better chance of success in regenerating periodontal tissue in elderly
      patients. This review examines and synthesizes recent data in support of the use
      of MSCs for periodontal regenerative therapy in patients. Additionally, we
      analyze the progress of the therapeutic use of exogenous MSCs in humans.

PMID- 30289441
TI  - Deletion of Adam6 in Mus musculus leads to male subfertility and deficits in
      sperm ascent into the oviduct.
AB  - The A disintegrin and metalloprotease domain-containing (ADAM) family of proteins
      is involved in cell adhesion, migration, proteolysis, and signaling. Many ADAMs
      are required for reproduction; however, the role of Adam6 has remained largely
      unknown. In the course of humanizing the mouse immunoglobulin heavy chain (IgH)
      locus we generated Adam6-deficient mice that demonstrate severe subfertility. We
      decided to elucidate the role of ADAM6 in fertility and explore the underlying
      mechanisms. Despite normal sperm development and motility, Adam6-deficient mice
      display diminished male fertility, have abnormal sperm adhesion, and most
      importantly cannot transition from uterus to oviduct. To test whether ADAM6 is
      required for sperm's binding to extracellular matrix components (ECM), we used a
      panel of ECM components and showed that unlike normal sperm, Adam6-deficient
      sperm cannot bind fibronectin, laminin, and tenascin. Reintroduction of Adam6
      into these deficient mice repaired sperm interaction with ECM, restored male
      fertility, and corrected the sperm transport deficit. Together our data suggest
      that ADAM6, either alone or in complex with other proteins, aids sperm transport
      through the female reproductive tract by providing a temporary site of attachment
      of sperm to ECM components prior to ascent into the oviduct.

PMID- 30289442
TI  - Quantifying Waddington's epigenetic landscape: a comparison of single-cell
      potency measures.
AB  - MOTIVATION: Estimating differentiation potency of single cells is a task of great
      biological and clinical significance, as it may allow identification of normal
      and cancer stem cell phenotypes. However, very few single-cell potency models
      have been proposed, and their robustness and reliability across independent
      studies have not yet been fully assessed. RESULTS: Using nine independent single
      cell RNA-Seq experiments, we here compare four different single-cell potency
      models to each other, in their ability to discriminate cells that ought to differ
      in terms of differentiation potency. Two of the potency models approximate
      potency via network entropy measures that integrate the single-cell RNA-Seq
      profile of a cell with a protein interaction network. The comparison between the
      four models reveals that integration of RNA-Seq data with a protein interaction
      network dramatically improves the robustness and reliability of single-cell
      potency estimates. We demonstrate that underlying this robustness is a
      correlation relationship, according to which high differentiation potency is
      positively associated with overexpression of network hubs. We further show that
      overexpressed network hubs are strongly enriched for ribosomal mitochondrial
      proteins, suggesting that their mRNA levels may provide a universal marker of a
      cell's potency. Thus, this study provides novel systems-biological insight into
      cellular potency and may provide a foundation for improved models of
      differentiation potency with far-reaching implications for the discovery of novel
      stem cell or progenitor cell phenotypes.

PMID- 30289443
TI  - Human-like layout algorithms for signalling hypergraphs: outlining requirements.
AB  - The use of signalling pathway hypergraphs represented as process description
      diagrams is steadily becoming more pervasive in the field of biology. This makes
      ever more evident the necessity for an effective automated layout that can
      replicate high-quality manually drawn diagrams. The complexity and idiosyncrasies
      of these diagrams, as well as the specific tasks the end users perform with them,
      mean that a layout must meet many requirements beyond the simple metrics used in
      existing automated computational approaches. In this paper we outline these
      requirements, examine existing ones and describe new ones. We demonstrate state
      of-the-art layout techniques enhanced with novel functionalities to meet part of
      the requirements. For comparatively small signalling pathways our enhanced
      algorithm provides results close to manually drawn layouts. In addition, we
      suggest technical approaches that may be suited for fulfilling the identified
      requirements currently not covered.

PMID- 30289444
TI  - Phase 1 Pharmacokinetic Trial of 2 Intravaginal Rings Containing Different Dose
      Strengths of Vicriviroc (MK-4176) and MK-2048.
AB  - Background: Vaginal rings (VRs) are a promising approach for sustained delivery
      of antiretroviral (ARV) medication to prevent human immunodeficiency virus (HIV)
      infection in women. Combination ARV VRs could increase efficacy. Methods: MTN
      028, a phase 1 trial in 19 HIV-uninfected women, evaluated 2 VRs containing
      vicriviroc (VCV) and MK-2048. Participants were randomized 2:1 to a low-dose
      (VCV, 91 mg; MK-2048, 10 mg) or original-dose (VCV, 182 mg; MK-2048, 30 mg) ring
      used for 28 days. Safety was assessed by documenting adverse events (AEs). Drug
      concentrations were evaluated in plasma, cervicovaginal fluid (CVF), and cervical
      tissue samples. Results: All AEs reported were grade 1 or 2, with no
      statistically significant differences in related genitourinary AEs or grade >=2
      AEs observed between arms (P = >.99). VCV/MK-2048 concentrations rose rapidly,
      with higher plasma area under the concentration-time curve (AUC) in the original
      dose arm (geometric mean ratio, 3.29 for VCV and 1.49 for MK-2048) and similar
      AUCs across arms for CVF samples. Cervical tissue concentrations were higher in
      the original-dose arm (geometric mean ratio, 7.94 for VCV and 6.45 for MK-2048),
      with greater drug released based on residual drug levels. Plasma and CVF
      concentrations for both drugs fell rapidly after ring removal. Conclusions: In
      this first study evaluating 2 doses of a combination VCV/MK-2048 VR, both rings
      were found to be safe and well tolerated. VCV and MK-2048 were detectable in
      plasma, CVF, and cervical tissue samples, and drug release and plasma drug
      exposure were higher for the original-dose than for the low-dose ring.

PMID- 30289446
TI  - Successful percutaneous lead extraction 15 years after a failed extraction
      attempt.

PMID- 30289445
TI  - Dysregulation of Cortisol Metabolism in Equine Pituitary Pars Intermedia
      Dysfunction.
AB  - Equine Cushing disease [pituitary pars intermedia dysfunction (PPID)] is a common
      condition of older horses, but its pathophysiology is complex and poorly
      understood. In contrast to pituitary-dependent hyperadrenocorticism in other
      species, PPID is characterized by elevated plasma ACTH but not elevated plasma
      cortisol. In this study, we address this paradox and the hypothesis that PPID is
      a syndrome of ACTH excess in which there is dysregulation of peripheral
      glucocorticoid metabolism and binding. In 14 horses with PPID compared with 15
      healthy controls, we show that in plasma, cortisol levels and cortisol binding to
      corticosteroid binding globulin were not different; in urine, glucocorticoid and
      androgen metabolites were increased up to fourfold; in liver, 11beta
      hydroxysteroid dehydrogenase type 1 (11beta-HSD1) expression was reduced; in
      perirenal adipose tissue, 11beta-HSD1 and carbonyl reductase 1 expression was
      increased; and tissue cortisol levels were not measurably different. The
      combination of normal plasma cortisol with markedly enhanced urinary cortisol
      metabolite excretion and dysregulated tissue-specific steroid-metabolizing
      enzymes suggests that cortisol clearance is increased in horses with PPID. We
      infer that the ACTH excess may be compensatory and pituitary pathology and
      autonomous secretion may be a secondary rather than primary pathology. It is
      possible that successful therapy in PPID may be targeted either at lowering ACTH
      or, paradoxically, at reducing cortisol clearance.

PMID- 30289447
TI  - Variability in a permanent cyanobacterial bloom: species-specific responses to
      environmental drivers.
AB  - Cyanobacterial blooms are characterized by intense growth of one or few species
      that will dominate the phytoplankton community for periods of few months to an
      entire year or more. However, even during persistent blooms, important seasonal
      changes among dominant species can be observed. Pampulha reservoir is a tropical
      eutrophic reservoir presenting permanent blooms. To identify the main species in
      this environment, a closer analysis performed by microscopy and 16S-rRNA DGGE
      revealed Cylindrospermopsis raciborskii as highly dominant throughout the year.
      The second most abundant group comprised species belonging to the Microcystis
      genus. They followed a well-defined seasonal pattern described by interesting
      species-specific ecological trends. During thermal stratification in the
      rainy/warmer season, C. raciborskii dominated in the water column, while
      Microcystis spp. were abundant at the end of the dry season, a period
      characterized by higher total phosphorus concentrations. Phylogenetic analyses
      confirmed the two dominant taxa and their seasonal trends. The results showed
      that cyanobacteria major controlling factors were strongly species dependent,
      shifting from physical/climate related (stratification) to more chemical driven
      (nutrients/eutrophication). Identifying these drivers is therefore essential for
      the understanding of the bloom dynamics and the real risks associated with each
      species, and to eventually adopt the most appropriate and effective management
      strategies.

PMID- 30289449
TI  - The screening and identification of the biological control fungi Chaetomium spp.
      against wheat common root rot.
AB  - Bipolaris sorokiniana is a soil-borne fungal pathogen causing common root rot in
      wheat, and is difficult to control through chemical and agricultural means.
      Chaetomium spp. have been documented as potential biological control agents for
      plant diseases. In this study, seven Chaetomium strains were screened for their
      abilities to control B. sorokiniana on agar plates. Strain 22-10 significantly
      inhibited the growth of B. sorokiniana on potato dextrose agar plates, up to
      66.7%. Its filtrate of liquid culture also inhibited the mycelial growth of B.
      sorokiniana, indicating that strain 22-10 produced secondary metabolites against
      B. sorokiniana. The incidence and disease indexes of common root rot
      significantly decreased in wheat after treatment with the crude extract of strain
      22-10. Six active compounds were purified from crude extract of this fungus
      culture against B. sorokiniana. Chaetoviridin A showed the highest efficiency to
      inhibit the growth of B. sorokiniana. Strain 22-10 was identified as Chaetomium
      globosum based on phylogenetic analysis of the rDNA internal transcribed spacer
      region and microscopic characteristics. The high control efficiency of strain 22
      10 of C. globosum against B. sorokiniana suggested it has potential to be a
      biocontrol agent for B. sorokiniana.

PMID- 30289448
TI  - Prokaryotic communities of Indo-Pacific giant barrel sponges are more strongly
      influenced by geography than host phylogeny.
AB  - Sponges harbor complex communities of microorganisms that carry out essential
      roles for the functioning and survival of their hosts. In some cases, genetically
      related sponges from different geographic regions share microbes, while in other
      cases microbial communities are more similar in unrelated sponges collected from
      the same location. To better understand how geography and host phylogeny cause
      variation in the prokaryotic community of sponges, we compared the prokaryotic
      community of 44 giant barrel sponges (Xestospongia spp.). These sponges belonged
      to six reproductively isolated genetic groups from eight areas throughout the
      Indo-Pacific region. Using Illumina sequencing, we obtained 440 000 sequences of
      the 16S rRNA gene V3V4 variable region that were assigned to 3795 operational
      taxonomic units (OTUs). The prokaryotic community of giant barrel sponges was
      characterized by 71 core OTUs (i.e. OTUs present in each specimen) that
      represented 57.5% of the total number of sequences. The relative abundance of
      these core OTUs varied significantly among samples, and this variation was
      predominantly related to the geographic origin of the sample. These results show
      that in giant barrel sponges, the variation in the prokaryotic community is
      primarily associated with geography as opposed to phylogenetic relatedness.

PMID- 30289450
TI  - Lack of Vitamin D Receptor Leads to Hyperfunction of Claudin-2 in Intestinal
      Inflammatory Responses.
AB  - Background: Vitamin D3 and vitamin D receptor (VDR) are involved in the
      pathogenesis of inflammatory bowel disease (IBD) and bacterial infection. Claudin
      2 is a junction protein that mediates paracellular water transport in epithelia.
      Elevation of Claudin-2 is associated with active IBD. However, VDR involved in
      epithelial junctions under inflammation and infection remains largely unknown. We
      investigated the mechanisms on how VDR and Claudin-2 are related in inflamed
      states. Methods: Using cultured VDR-/- enteroids, human intestinal epithelial
      cells, VDR-/- mice with Salmonella- or DSS-colitis, and human IBD samples, we
      investigated the mechanisms how VDR and Claudin-2 are related in inflamed states.
      Results: After Salmonella infection had taken place, we observed significantly
      enhanced Claudin-2 and an increased bacterial invasion and translocation. A lack
      of VDR regulation led to a robust increase of Claudin-2 at the mRNA and protein
      levels post-infection. In DSS-treated VDR-/- mice, Claudin-2 was significantly
      increased. Location and quantification of Claudin-2 protein in the mouse colons
      treated with DSS also confirmed these results. Inflammatory cytokines were
      significantly higher in the serum and mRNA levels in intestine, which are known
      to increase Claudin-2. Furthermore, in inflamed intestine of ulcerative colitis
      patients, VDR expression was low and Claudin-2 was enhanced. Mechanistically, we
      identified the enhanced Claudin-2 promoter activity through the binding sites of
      NF-kappaB and STAT in inflamed VDR-/- cells. Conclusions: Our studies have
      identified a new role for intestinal epithelial VDR in regulating barrier
      functions in the context of infection and inflammation.

PMID- 30289451
TI  - Early recurrent mitral regurgitation due to MitraClip migration.

PMID- 30289452
TI  - Coronary lithoplasty: a novel treatment for stent underexpansion.

PMID- 30289453
TI  - Glycoengineered Antibodies: Towards the Next-Generation of Immunotherapeutics.
AB  - Monoclonal antibodies (mAbs) are currently the largest and fastest growing class
      of biopharmaceuticals, and they address unmet medical needs e.g., in oncology and
      in auto-immune diseases. Their clinical efficacy and safety is significantly
      affected by the structure and composition of their glycosylation profile which is
      commonly heterogeneous, heavily dependent on the manufacturing process, and thus
      susceptible to variations in the cell culture conditions. Glycosylation is
      therefore considered a critical quality attribute (CQA) for mAbs. Commonly, in
      currently marketed therapeutic mAbs, the glycosylation profile is suboptimal in
      terms of biological properties such as antibody-dependent cell-mediated
      cytotoxicity (ADCC) or may give rise to safety concerns due to the presence of
      non-human glycans.This article will review recent innovative developments in
      chemo-enzymatic glycoengineering, which allow generating mAbs carrying single,
      well-defined, uniform Fc glycoforms, which confers the desired biological
      properties for the target application. This approach offers significant benefits
      such as enhanced Fc effector functions, improved safety profiles, higher batch-to
      batch consistency, decreased risks related to immunogenicity and manufacturing
      process changes, and the possibility to manufacture mAbs, in an economical
      manner, in non-mammalian expression systems. Overall, this approach could
      facilitate and reduce mAb manufacturing costs which in turn would translate into
      tangible benefits for both patients and manufacturers. The first glycoengineered
      mAbs are about to enter clinical trials and it is expected that, once
      glycoengineering reagents are available at affordable costs, and in-line with
      regulatory requirements, that targeted remodelling of antibody Fc glycosylation
      will become an integral part in manufacturing the next-generation of
      immunotherapeutics.

PMID- 30289454
TI  - Dusp6 is a genetic modifier of growth through enhanced ERK activity.
AB  - Like other single gene disorders, muscular dystrophy displays a range of
      phenotypic heterogeneity even with the same primary mutation. Identifying genetic
      modifiers capable of altering the course of muscular dystrophy is one approach to
      deciphering gene-gene interactions that can be exploited for therapy development.
      To this end, we used an intercross strategy in mice to map modifiers of muscular
      dystrophy. We interrogated genes of interest in an interval on mouse chromosome
      10 associated with body mass in muscular dystrophy as skeletal muscle contributes
      significantly to total body mass. Using whole genome sequencing of the two
      parental mouse strains combined with deep RNA sequencing, we identified the
      Met62Ile substitution in the Dusp6 gene from the DBA/2J mouse strain. DUSP6 is a
      broadly expressed dual specificity phosphatase protein, which binds and
      dephosphorylates ERK, leading to decreased ERK activity. We found that the
      Met62Ile substitution reduced the interaction between DUSP6 and ERK resulting in
      increased ERK phosphorylation and ERK activity. In dystrophic muscle, DUSP6
      Met62Ile is strongly upregulated to counteract its reduced activity. We found
      that myoblasts from the DBA/2J background were insensitive to a specific small
      molecule inhibitor of DUSP6, while myoblasts expressing the canonical DUSP6
      displayed enhanced proliferation after exposure to DUSP6 inhibition. These data
      identify DUSP6 as an important regulator of ERK activity in the setting of muscle
      growth and muscular dystrophy.

PMID- 30289455
TI  - DNA phosphorothioate modification - a new multi-functional epigenetic system in
      bacteria.
AB  - Synthetic phosphorothioate (PT) internucleotide linkages, in which a nonbridging
      oxygen is replaced by a sulfur atom, share similar physical and chemical
      properties with phosphodiesters but confer enhanced nuclease tolerance on
      DNA/RNA, making PTs a valuable biochemical and pharmacological tool.
      Interestingly, PT modification was recently found to occur naturally in bacteria
      in a sequence-selective and RP configuration-specific manner. This oxygen-sulfur
      swap is catalysed by the gene products of dndABCDE, which constitute a defence
      barrier with DndFGH in some bacterial strains that can distinguish and attack non
      PT-modified foreign DNA, resembling DNA methylation-based restriction
      modification (R-M) systems. Despite their similar defensive mechanisms, PT- and
      methylation-based R-M systems have evolved to target different consensus contexts
      in the host cell because when they share the same recognition sequences, the
      protective function of each can be impeded. The redox and nucleophilic properties
      of PT sulfur render PT modification a versatile player in the maintenance of
      cellular redox homeostasis, epigenetic regulation and environmental fitness. The
      widespread presence of dnd systems is considered a consequence of extensive
      horizontal gene transfer, whereas the lability of PT during oxidative stress and
      the susceptibility of PT to PT-dependent endonucleases provide possible
      explanations for the ubiquitous but sporadic distribution of PT modification in
      the bacterial world.

PMID- 30289456
TI  - Pulsatile temporal vein caused by severe tricuspid regurgitation.

PMID- 30289457
TI  - Can I still eat it? Using problem-based learning to test the 5-second rule and
      promote scientific literacy.
AB  - Defining appropriate student learning outcomes for general education science
      courses is a daunting task. We must ask ourselves how to best prepare our
      students to understand the role of science in their lives and in society at
      large. In the era of social media and armchair experts, life-changing scientific
      advancements such as vaccination are being dismissed or actively resisted,
      emphasizing the critical need to teach science literacy skills. One active
      classroom method known as problem-based learning promotes self-motivated learning
      and synthesis skills that, when applied in a science-literacy context, can
      provide students with the ability to generate informed opinions on new scientific
      advances throughout their lifetime. This piece describes one such problem-based
      course, designed to tackle the scientific basis (or lack thereof) of the 5-second
      rule for eating food dropped on the floor. In this course, first year students
      experimentally engage this issue, while also applying their developing skill set
      to sort out scientific controversies such as vaccine safety and genetically
      modified foods.

PMID- 30289458
TI  - Postinfarction right ventricular wall dissection with left-to-right shunting.
AB  - Ventricular septal rupture is an uncommon fatal complication of acute myocardial
      infarction. In rare cases, the rupture can extend into the right ventricular free
      wall and cause intramyocardial dissection. We describe the case of a patient who
      developed postinfarction right ventricular free wall dissection with left-to
      right shunting and successfully underwent patch repair.

PMID- 30289459
TI  - Helicobacter pylori induces intracellular galectin-8 aggregation around damaged
      lysosomes within gastric epithelial cells in a host O-glycan-dependent manner.
AB  - Galectin-8, a beta-galactoside-binding lectin, is upregulated in the gastric
      tissues of rhesus macaques infected with Helicobacter pylori. In this study, we
      found that H. pylori infection triggers intracellular galectin-8 aggregation in
      human-derived AGS gastric epithelial cells, and that these aggregates colocalize
      with lysosomes. Notably, this aggregation is markedly reduced following the
      attenuation of host O-glycan processing. This indicates that H. pylori infection
      induces lysosomal damage, which in turn results in the accumulation of cytosolic
      galectin-8 around damaged lysosomes through the recognition of exposed vacuolar
      host O-glycans. H. pylori-induced galectin-8 aggregates also colocalize with
      autophagosomes, and galectin-8 ablation reduces the activation of autophagy by H.
      pylori. This suggests that galectin-8 aggregates may enhance autophagy activity
      in infected cells. We also observed that both autophagy and NDP52, an autophagy
      adaptor, contribute to the augmentation of galectin-8 aggregation by H. pylori.
      Additionally, vacuolating cytotoxin A, a secreted H. pylori cytotoxin, may
      contribute to the increased galectin-8 aggregation and elevated autophagy
      response in infected cells. Collectively, these results suggest that H. pylori
      promotes intracellular galectin-8 aggregation, and that galectin-8 aggregation
      and autophagy may reciprocally regulate each other during infection.

PMID- 30289460
TI  - An Adjuvant That Increases Protective Antibody Responses to Polysaccharide
      Antigens and Enables Recall Responses.
AB  - Protection against encapsulated bacteria can be elicited using polysaccharide
      vaccines. These antigens often behave as T-cell-independent type 2 antigens (TI-2
      Ags). However, TI-2 Ags, including pneumococcal polysaccharides, often elicit
      weak immunoglobulin G (IgG) responses and are refractive to boosting. Conjugate
      vaccines have not completely overcome this challenge and hence, alternative
      strategies are required to enhance polysaccharide vaccine responses. Herein, we
      describe an adjuvant consisting of a Toll-like receptor and C-type lectin
      receptor agonist pairing that significantly increases primary immunoglobulin M
      and IgG responses to TI-2 Ags as well as enables significant boosting when
      coadministered with polysaccharide vaccines. Consistent with this, the adjuvant
      significantly increased the generation of both TI-2 memory B cells and long-lived
      antibody secreting cells. Adjuvant effects were highly dependent on B-cell
      intrinsic MyD88, but not Trif expression. Importantly, coadministration of the
      adjuvant with the Pneumovax vaccine significantly increased the protective
      efficacy of vaccination in a lethal challenge mouse model of pneumococcal
      respiratory infection. Collectively, these data provide evidence that B-cell
      directed adjuvants have promise in significantly improving the quality and
      quantity of serologic and B-cell memory responses to clinically relevant
      polysaccharide vaccines.

PMID- 30289461
TI  - Environmental health in Australia: overlooked and underrated.
AB  - Improvements in environmental health have had the most significant impact on
      health status. In Australia, life expectancy has significantly increased through
      provision of vaccination, safe food and drinking water, appropriate sewage
      disposal and other environmental health measures. Yet the profession that is
      instrumental in delivering environmental health services at the local community
      level is overlooked. Rarely featuring in mainstream media, the successes of
      Environmental Health Officers (EHOs) are invisible to the general public. As a
      consequence, students entering university are unaware of the profession and its
      significant role in society. This has resulted in there being too few EHOs to
      meet the current regulatory requirements, much less deal with the emerging
      environmental health issues arising as a consequence of changing global
      conditions including climate change. To futureproof Australian society and public
      health this workforce issue, and the associated oversight of environmental health
      must be addressed now.

PMID- 30289462
TI  - Morphological and Molecular Identification of Phlebotomus mascittii Grassi, 1908
      Populations From Slovenia.
AB  - The Transphlebotomus subgenus has been drawing attention in last decade due to
      the uncertain vector capacity and cryptic life history of the group. During a
      2015 entomological survey, Phlebotomine flies were collected in western locations
      of Slovenia, with a total of 22 specimens of the Transphlebotomus subgenus
      collected. In addition to morphological identifications, we confirmed the
      presence of Phlebotomus mascittii Grassi, 1908 (Diptera: Psychodidae) by
      nucleotide sequences of the mitochondrial cytochrome b gene. During the study, we
      found that P. mascittii is most abundant in the area of coastal-karst region of
      Slovenia, while in rare occasions can also be collected in Northeastern part of
      the country, near the Austrian border. Vector competence of P. mascitii, like all
      other member species of the Transphlebotomus subgenus, is unclear, but potential
      to transmit Leishmania (Kinetoplastida: Trypanosomatidae) pathogens or
      phleboviruses is strongly suspected.

PMID- 30289465
TI  - Corrigendum.

PMID- 30289463
TI  - Engineered dCas9 with reduced toxicity in bacteria: implications for genetic
      circuit design.
AB  - Large synthetic genetic circuits require the simultaneous expression of many
      regulators. Deactivated Cas9 (dCas9) can serve as a repressor by having a small
      guide RNA (sgRNA) direct it to bind a promoter. The programmability and
      specificity of RNA:DNA basepairing simplifies the generation of many orthogonal
      sgRNAs that, in theory, could serve as a large set of regulators in a circuit.
      However, dCas9 is toxic in many bacteria, thus limiting how high it can be
      expressed, and low concentrations are quickly sequestered by multiple sgRNAs.
      Here, we construct a non-toxic version of dCas9 by eliminating PAM (protospacer
      adjacent motif) binding with a R1335K mutation (dCas9*) and recovering DNA
      binding by fusing it to the PhlF repressor (dCas9*_PhlF). Both the 30 bp PhlF
      operator and 20 bp sgRNA binding site are required to repress a promoter. The
      larger region required for recognition mitigates toxicity in Escherichia coli,
      allowing up to 9600 +/- 800 molecules of dCas9*_PhlF per cell before growth or
      morphology are impacted, as compared to 530 +/- 40 molecules of dCas9. Further,
      PhlF multimerization leads to an increase in average cooperativity from n = 0.9
      (dCas9) to 1.6 (dCas9*_PhlF). A set of 30 orthogonal sgRNA-promoter pairs are
      characterized as NOT gates; however, the simultaneous use of multiple sgRNAs
      leads to a monotonic decline in repression and after 15 are co-expressed the
      dynamic range is <10-fold. This work introduces a non-toxic variant of dCas9,
      critical for its use in applications in metabolic engineering and synthetic
      biology, and exposes a limitation in the number of regulators that can be used in
      one cell when they rely on a shared resource.

PMID- 30289464
TI  - The antimicrobial photodynamic inactivation resistance of Candida albicans is
      modulated by the Hog1 pathway and the Cap1 transcription factor.
AB  - Candida albicans is the most important fungal pathogen afflicting humans,
      particularly immunocompromised patients. However, currently available antifungal
      drugs are limited and ineffective against drug-resistant strains. The development
      of new drugs or alternative therapeutic approaches to control fungal infections
      is urgent and necessary. Photodynamic inactivation (PDI) is a new promising
      therapy for eradicating microorganism infections through combining visible light,
      photosensitizers, and oxygen to generate reactive oxygen species (ROS). Although
      cytoprotective responses induced by photodynamic therapy (PDT) have been well
      studied in cancer cells, the mechanisms by which C. albicans responds to PDI are
      largely unknown. In this study, we first demonstrated that PDI induces C.
      albicans Hog1p activation. Deletion of any of the SSK2, PBS2, and HOG1 genes
      significantly decreased the survival rate after photochemical reactions,
      indicating that the Hog1 SAPK pathway is required for tolerance to PDI.
      Furthermore, the basic leucine zipper transcription factor Cap1 that regulates
      several downstream antioxidant genes was highly expressed during the response to
      PDI, and loss of CAP1 also resulted in decreased C. albicans survival rates. This
      study demonstrates the importance of the Hog1 SAPK and the Cap1 transcription
      factor, which regulates in resistance to PDI-mediated oxidative stress in C.
      albicans. Understanding the mechanisms by which C. albicans responds to PDI and
      consequently scavenges ROS will be very useful for the further development of
      therapeutics to control fungal infectious diseases, particularly those of the
      skin and mucosal infections.

PMID- 30289466
TI  - Health and mass unemployment events-developing a framework for preparedness and
      response.
AB  - Background: Mass unemployment events are not uncommon yet the impact on health is
      not well recognised. There is a need for a preparedness and response framework,
      as exists for other events that threaten population health. Methods: Framework
      informed by a narrative review of the impact of mass unemployment on health
      (studies published in English from 1990 to 2016), and qualitative data from 23
      semi-structured interviews with individuals connected to historical national and
      international events, addressing gaps in published literature on lessons learnt
      from past responses. Results: Economic and employment shock triggered by mass
      unemployment events have a detrimental impact on workers, families and
      communities. We present a public health informed response framework which
      includes (i) identify areas at risk, (ii) develop an early warning system, (iii)
      mobilise multi-sector action including health and community, (iv) provision of
      support across employment, finance and health (v) proportionate to need, (vi)
      extend support to family members and (vii) communities and (viii) evaluate and
      learn. Conclusion: Mass unemployment events have an adverse impact on the health,
      financial and social circumstances of workers, families, and communities. This is
      the first framework for action to mitigate and address the detrimental impact of
      mass unemployment events on population health.

PMID- 30289467
TI  - A prospective survey of Aspergillus spp. in respiratory tract samples: Species
      identification and susceptibility patterns.
AB  - We analyzed the species distribution and susceptibility patterns of 433 strains
      of Aspergillus spp. isolated from respiratory samples of 419 in-patients included
      in multicenter prospective study (FUNGAE-IFI) between July 2014 and October 2015.
      Identification was carried out by conventional methods at each participating
      center and by molecular sequencing of a portion of the beta-tubulin gene at one
      of the centers. In vitro susceptibility was evaluated by broth microdilution
      methods and using the E-test (for cryptic species). Species identified included
      249 A. fumigatus sensu stricto, 60 A. terreus sensu stricto, 47 A. flavus sensu
      stricto, 44 A. tubingensis, 18 A. niger sensu stricto , five A. nidulans sensu
      stricto, three A. tamarii, two A. calidoustus, two A. carneus, one A. acuelatus,
      one A. carbonarius, and one A. sydowii. Cryptic species were found in 12.5% of
      isolates (n = 54). The frequency of non-wild-type isolates for amphotericin B was
      3.4% (n = 15) of the isolates tested and for azoles 3% (n = 10). None of the
      Aspergillus spp. were non-wild type to echinocandins. Of the 54 cryptic species
      only two strains were non-wild-type strains by microdilution method (3.7%) (two
      A. tubingensis, one to amphotericin B and another one to voriconazole) and by E
      test method five strains of A. tubingensis showed high minimal inhibitory
      concentration (MIC) to amphotericin B (11.4%) and five to azoles (12.1%), one A.
      calidoustus strain showed high MICs for three azoles (50%), A. carneus to
      itraconazole (100%) and A. sydowii to amphotericin B and itraconazole (100%).
      These results provide relevant information on susceptibility patterns, frequency,
      and epidemiology of species involved in respiratory tract samples and of the
      incidence of recently described cryptic species.

PMID- 30289470
TI  - Knock-out IFNL4 gene variant is associated with protection from sexually
      transmitted HIV-1 infection.
AB  - The IFNL4 knock-out allele (rs368234815-TT) is associated with spontaneous and
      IFNA-dependent cure of HCV. The role of this polymorphism in susceptibility to
      HIV-1 infection is controversial. This study is aimed to assess the association
      of this knock-out IFNL4 gene variant and sexually transmitted HIV-1 infection.
      228 HIV-1 positive and 136 HIV-exposed seronegatives were investigated for their
      association with IFNL4 rs368234815 genotypes. The IFNL4 ?G functional allele is
      associated to increased susceptibility to HIV-1 infection through sexual route
      OR: 2.1 95% CI (1.2-3.6), P=0.004. A meta-analysis including an IDU population
      suggests a codominant mode of inheritance of this risk factor OR: 2.0 95% CI (1.3
      3.2), P=0.001.

PMID- 30289471
TI  - A 15-Month-Old Boy With a Rash on His Hands and Feet.

PMID- 30289469
TI  - Oxidative damage to epigenetically methylated sites affects DNA stability,
      dynamics and enzymatic demethylation.
AB  - DNA damage can affect various regulatory elements of the genome, with the
      consequences for DNA structure, dynamics, and interaction with proteins remaining
      largely unexplored. We used solution NMR spectroscopy, restrained and free
      molecular dynamics to obtain the structures and investigate dominant motions for
      a set of DNA duplexes containing CpG sites permuted with combinations of 5
      methylcytosine (mC), the primary epigenetic base, and 8-oxoguanine (oxoG), an
      abundant DNA lesion. Guanine oxidation significantly changed the motion in both
      hemimethylated and fully methylated DNA, increased base pair breathing, induced
      BI->BII transition in the backbone 3' to the oxoG and reduced the variability of
      shift and tilt helical parameters. UV melting experiments corroborated the NMR
      and molecular dynamics results, showing significant destabilization of all
      methylated contexts by oxoG. Notably, some dynamic and thermodynamic effects were
      not additive in the fully methylated oxidized CpG, indicating that the introduced
      modifications interact with each other. Finally, we show that the presence of
      oxoG biases the recognition of methylated CpG dinucleotides by ROS1, a plant
      enzyme involved in epigenetic DNA demethylation, in favor of the oxidized DNA
      strand. Thus, the conformational and dynamic effects of spurious DNA oxidation in
      the regulatory CpG dinucleotide can have far-reaching biological consequences.

PMID- 30289473
TI  - Timing of administration of dengue vaccine in travellers with a recent confirmed
      dengue infection.

PMID- 30289474
TI  - Late surgical explantation of a transcatheter heart valve in a patient with a
      porcelain aorta.
AB  - Structural valve deterioration is a well-studied phenomenon in bioprosthetic
      heart valves. Conversely, structural valve deterioration after transcatheter
      aortic valve implantation is not as well-elucidated. Therefore, late surgical
      explantation after transcatheter aortic valve implantation is an infrequent
      procedure, and thus, surgical findings and management of such cases remain
      unclear, particularly in patients previously labelled as 'inoperable' or at 'high
      risk'. Herein, we report the case of a late surgical explantation of a
      transcatheter heart valve (THV) 7 years after its implantation in a patient with
      a porcelain aorta and periprosthetic regurgitation.

PMID- 30289475
TI  - Has the optimal therapy for invasive candidiasis now been defined?

PMID- 30289472
TI  - Genomic Analyses of Human European Diversity at the Southwestern Edge: Isolation,
      African Influence and Disease Associations in the Canary Islands.
AB  - Despite the genetic resemblance of Canary Islanders to other southern European
      populations, their geographical isolation and the historical admixture of
      aborigines (from North Africa) with sub-Saharan Africans and Europeans have
      shaped a distinctive genetic makeup that likely affects disease susceptibility
      and health disparities. Based on single nucleotide polymorphism array data and
      whole genome sequencing (30*), we inferred that the last African admixture took
      place ~14 generations ago and estimated that up to 34% of the Canary Islander
      genome is of recent African descent. The length of regions in homozygosis and the
      ancestry-related mosaic organization of the Canary Islander genome support the
      view that isolation has been strongest on the two smallest islands. Furthermore,
      several genomic regions showed significant and large deviations in African or
      European ancestry and were significantly enriched in genes involved in prevalent
      diseases in this community, such as diabetes, asthma, and allergy. The most
      prominent of these regions were located near LCT and the HLA, two well-known
      targets of selection, at which 40-50% of the Canarian genome is of recent African
      descent according to our estimates. Putative selective signals were also
      identified in these regions near the SLC6A11-SLC6A1, KCNMB2, and PCDH20-PCDH9
      genes. Taken together, our findings provide solid evidence of a significant
      recent African admixture, population isolation, and adaptation in this part of
      Europe, with the favoring of African alleles in some chromosome regions. These
      findings may have medical implications for populations of recent African
      ancestry.

PMID- 30289476
TI  - Long-term stability of curve of Spee levelled with continuous archwires in
      subjects with different vertical patterns: a retrospective study.
AB  - Objectives: The aim of the study was to evaluate the curve of Spee (COS)
      stability in patients treated with continuous archwires with different vertical
      patterns. Methods: The study sample consisted of 60 patients (28 males, 32
      females; mean age 19.8 +/- 1.4 years) presenting with COS depth of at least2 mm
      at baseline. For each subject, lateral cephalograms and dental casts were
      available before treatment (T1), at the end of orthodontic therapy (T2), and 2
      years after the end of treatment (T3). All subjects were divided into three
      groups according to vertical facial patterns. Cephalometric parameters were used
      to evaluate the dental movements after treatment. COS depth was measured on
      digital casts. Mean differences between vertical facial subgroups were contrasted
      by means of analysis of variance test (P < 0.01). Results: In low-angle subjects,
      COS levelling occurred through advancement and intrusion of lower incisors,
      whereas in high-angle patients, the COS was flattened through extrusion and
      uprighting of lower posterior teeth. In the low-angle group, a significant
      relapse of lower incisors inclination was observed. Differently, the high-angle
      group exhibited a greater stability of COS obtained by stable extrusion of
      posterior teeth. Conclusions: The long-term instability of flared incisors
      determined the relapse of overbite and COS depth in the low-angle group.

PMID- 30289477
TI  - RRSP and RID Effector Domains Dominate Virulence Impact of Vibrio vulnificus
      MARTX Toxin.
AB  - Background: The bacterial pathogen Vibrio vulnificus causes severe septic
      foodborne infections. The multifunctional autoprocessing repeats-in-toxins
      (MARTX) toxin is an important secreted virulence factor. The effector domain
      region is essential for lethal intestinal infection in mice, but the contribution
      of each of the five effector domains to infection has not been investigated.
      Methods: V. vulnificus mutants with varying effector domain content were
      inoculated intragastrically to mice and time-to-death was monitored to establish
      the contribution of each effector domain to overall virulence. Each strain was
      also tested for bacterial dissemination from the intestine to internal organs and
      for inhibition of phagocytosis. Results: The effector domain region was required
      for V. vulnificus to inhibit phagocytosis by J774 macrophages, but no single
      effector domain was required. No single MARTX effector domain was necessary for
      bacterial dissemination. Nonetheless, overall survival of infected mice did
      differ dependent upon the infecting V. vulnificus strain. Removal of rid or rrsp
      significantly reduced V. vulnificus virulence potential, while deletion of duf1
      or abh accelerated time to death. Conclusion: RID and RRSP each exert greater
      effects on virulence compared to other MARTX domains suggesting that modulation
      of Rho/Ras family GTPases is a critical function of the toxin during intestinal
      infection.

PMID- 30289478
TI  - Isavuconazole versus Caspofungin in the Treatment of Candidemia and Other
      Invasive Candida Infections: The ACTIVE Trial.
AB  - Background: Isavuconazole was compared to caspofungin followed by oral
      voriconazole in a phase 3, randomized, double-blind, multinational clinical trial
      (ACTIVE; NCT00413218) for primary treatment of patients with candidemia or
      invasive candidiasis. Methods: Adult patients were randomized 1:1 to
      isavuconazole (200 mg IV TID for 2 days, followed by 200 mg IV QD) or caspofungin
      (70 mg IV QD on day 1, followed by 50 mg IV QD [70 mg in patients >80 kg]) for a
      maximum of 56 days. After day 10, patients could switch to oral isavuconazole
      (isavuconazole arm) or voriconazole (caspofungin arm). The primary efficacy
      endpoint was successful overall response at end of IV therapy (EOIVT) in patients
      with proven infection who received >=1 dose of study drug (modified-intent-to
      treat [mITT] population). The pre-specified noninferiority margin was 15%.
      Secondary outcomes (mITT) were successful overall response at 2 weeks after end
      of treatment, all-cause mortality at days 14 and 56, and safety. Results: Of 450
      patients randomized, 400 comprised the mITT population. Baseline characteristics
      were balanced between groups. Successful overall response at EOIVT was observed
      in 60.3% of patients in the isavuconazole arm, and 71.1% in the caspofungin arm,
      (adjusted difference [95% confidence interval] -10.8 [-19.9, -1.8]). The
      secondary endpoints, all-cause mortality, and safety were similar between arms,
      while median time to clearance of the bloodstream was comparable in both groups.
      Conclusions: This study did not demonstrate the non-inferiority of isavuconazole
      to caspofungin for primary treatment of invasive candidiasis. Secondary endpoints
      were similar between both groups.

PMID- 30289479
TI  - Prevalence of venous thromboembolism after lung surgery in China: a single
      centre, prospective cohort study involving patients undergoing lung resections
      without perioperative venous thromboembolism prophylaxis.
AB  - OBJECTIVES: Venous thromboembolism (VTE) is a common postoperative complication.
      Previous studies have shown that the incidence of VTE after major thoracic
      surgery ranges from 2.3% to 15%. However, there have been no such data from China
      so far. To evaluate the incidence of postoperative VTE, we conducted a single
      centre, prospective cohort study. METHODS: Patients who underwent lung resections
      between July 2016 and March 2017 were enrolled in this study. None of the
      patients received any prophylaxis perioperatively. All patients were screened for
      deep venous thrombosis (DVT) using non-invasive duplex lower-extremity
      ultrasonography 30 days before surgery and within 30 days after surgery and
      before discharge. Chest tomography, pulmonary embolism protocol was carried out
      if patients had one of the following conditions: (i) typical symptoms of
      pulmonary embolism, (ii) high Caprini score (>=9 points) and (iii) newly
      diagnosed postoperative DVT. RESULTS: Two hundred and sixty-two patients
      undergoing lung surgery were enrolled, including 115 benign and 147 malignant
      disease cases. The procedures included 84 sublobar lung resections, 161
      lobectomies, 5 pneumonectomies and 12 mixed procedures. The overall postoperative
      incidence of VTE was 11.5% (30 of 262). Twenty-four patients were diagnosed with
      DVT (80.0%) and 6 with DVT + pulmonary embolism (20.0%). None of the patients
      diagnosed with VTE had obvious symptoms of VTE. The median time for VTE detection
      was 5 days postoperatively. The incidence of VTE was 7.0% in patients with benign
      lung diseases and 15.0% in those with malignant lung diseases (P < 0.05). Using
      the Caprini risk assessment model, 63 cases were scored as low risk, 179 as
      moderate risk and 20 as high risk, and each group had an incidence of
      postoperative VTE of 0%, 12.3% (22 of 179) and 40.0% (8 of 20), respectively (P <
      0.05). In patients with lung cancer, 98% were moderate or high risk, and only 3
      patients were scored in the low risk category. The incidence of VTE in patients
      at moderate risk and high risk was 12.0% and 36.8%, respectively, while it was 0
      in low-risk patients. CONCLUSIONS: The following conclusions were drawn: (i) the
      overall incidence of postoperative VTE after lung surgery without VTE prophylaxis
      is substantial; (ii) lower-extremity ultrasonography was helpful in detecting
      asymptomatic DVT in symptomatic or high-risk patients; and (iii) VTE prophylaxis
      should be considered as a mandatory part of perioperative care. Clinical trial
      registration number: ChiCTR-EOC-17010577.

PMID- 30289480
TI  - Resurgence of diphtheria in Yemen due to population movement.

PMID- 30289481
TI  - Low truncal muscle area on chest computed tomography: a poor prognostic factor
      for the cure of early-stage non-small-cell lung cancer.
AB  - OBJECTIVES: Depletion in skeletal muscle is closely associated with limited
      physical ability and high mortality. In this study, we evaluated the prognostic
      significance of skeletal muscle depletion in patients with early-stage non-small
      cell lung cancer. METHODS: A retrospective analysis of patients with pathological
      stages I-II lung cancer, who underwent curative resection between 2009 and 2013,
      was conducted. The truncal muscle index (TMI) (area/height2) at the first lumbar
      vertebral level was measured by preoperative axial computed tomography. Overall
      survival and recurrence-free survival were compared between the lowest gender
      specific quartile of the TMI and the other quartiles. RESULTS: A total of 314
      subjects were included in the study. The cumulative 5-year recurrence-free and
      overall survival rates were significantly shorter in patients with lower TMIs
      (69% vs 83.5%, P = 0.028; 64.8% vs 80.1%, P = 0.003, respectively). In
      multivariable models, the TMI was identified as an independent prognostic factor
      for overall survival (P =  0.017, hazard ratio 1.84, 95% confidence interval 1.12
      3.05), after adjusting for age, gender, preoperative serum albumin,
      carcinoembryonic antigen, neutrophil to lymphocyte ratio and pathological stage.
      CONCLUSIONS: A low preoperative TMI was associated with a poor postoperative
      outcome in patients with early-stage non-small-cell lung cancer. This factor may
      be included in the preoperative assessment of patients, for whom surgical
      intervention is considered.

PMID- 30289482
TI  - Zika virus and sexual transmission: updated preconception guidance.

PMID- 30289483
TI  - Should we consider marijuana use in relation to physical activity and cognitive
      impairment in persons with HIV infection?

PMID- 30289484
TI  - Dropping aspirin in patients with atrial fibrillation undergoing percutaneous
      coronary intervention: a jump with a weak parachute?

PMID- 30289485
TI  - Phase 2a Safety, Pharmacokinetics, and Acceptability of Dapivirine Vaginal Rings
      in US Postmenopausal Women.
AB  - Background: Postmenopausal women have unique sociobiological human
      immunodeficiency virus (HIV) risks. We evaluated the safety, pharmacokinetics,
      and acceptability of a microbicide dapivirine (DPV) vaginal ring (VR) versus
      placebo in postmenopausal women. Methods: We enrolled 96 HIV-negative
      postmenopausal US women in a phase 2a double-blind, randomized (3:1) trial of
      monthly VRs containing 25 mg DPV or placebo used continuously for 12 weeks. We
      assessed safety by adverse events (AEs). DPV concentrations were quantified in
      plasma and vaginal fluid. Steady-state concentrations were analyzed at 4, 8, and
      12 weeks using repeated measures ANOVA. We assessed acceptability by self-report.
      Results: We found no differences in the proportion of women with related grade 2
      or higher reproductive system AEs (DPV: 6/72 (8%), placebo: 3/24 (13%), P = .68)
      or grade 3 or higher AEs (DPV: 4/72 (6%), placebo: 0/24 (0%), P = .57). In the
      DPV arm, 2/72 (3%) declined to resume product use due to AEs. Median DPV
      concentrations in plasma (262.0 pg/mL at week 12) and vaginal fluid (40.6 ng/mg
      at week 12) were constant over 12 weeks and exceeded the in vitro 50% effective
      concentration by 5000-fold in vaginal fluid by week 4. VR acceptability was high;
      84/93 (90%) "very much liked or liked" the VR. Conclusions: DPV VRs were safe,
      well tolerated, and acceptable in postmenopausal women. Plasma concentrations
      were comparable to published data on DPV use in reproductive-age women (median
      plasma concentration: 264 pg/mL). Given the reassuring safety and pharmacokinetic
      data, the DPV VR is promising for preexposure prophylaxis in postmenopausal
      women. Clinical Trials Registration: ClinicalTrials.gov identifier: NCT02010593.

PMID- 30289486
TI  - Airborne acquisition of Pneumocystis in bronchoscopy units: a hidden danger to
      healthcare workers.
AB  - The possible presence of Pneumocystis in a bronchoscopy unit of a tertiary
      hospital was examined by detecting Pneumocystis-specific DNA by polymerase chain
      reaction in prospectively obtained samples of oropharyngeal wash from seven
      healthcare workers (HCWs) and air from three areas of the unit at different time
      points (baseline, days +15,+30,+60,+90 after initiation of the study). Positive
      samples were genotyped at two genetic loci: the mitochondrial large subunit
      ribosomal RNA (mtLSUrRNA) fragment by direct sequencing and the gene for
      dihydropteroate synthase (DHPS) by restriction fragment-length polymorphism.
      Pneumocystis DNA was identified in 13/24 samples from HCWs, in 4/14 air samples
      and also in two patients with Pneumocystis pneumonia (PcP) and another with a
      Pneumocystis-associated disease subjected to bronchoscopy on days +15 and +60
      after initiation of the study. The HCWs harbored a high rate of mtLSU-rRNA
      genotypes 1 and 3 and samples from air and patients with only genotype 3. DHPS
      mutations related to sulpha resistance were detected in three samples from HCWs
      and in one from air; 65% of the positive samples showed genotypic concordance.
      The study demonstrates that HCWs of bronchoscopy units represent a new dynamic
      reservoir and a possible source of infection for human Pneumocystis species,
      including DHPS genotypes related to sulpha resistance that could be transmitted
      within hospitals to immunosuppressed hosts in whom a PcP can develop. The results
      provide the first evidence of the risk of Pneumocystis transmission in the
      bronchoscopy units and arguments to improve prevention and control of this
      infection in nosocomial setting.

PMID- 30289487
TI  - The NTP binding site of the polymerase ribozyme.
AB  - A previously developed RNA polymerase ribozyme uses nucleoside triphosphates
      (NTPs) to extend a primer 3'-terminus, templated by an RNA template with good
      fidelity, forming 3'-5'-phosphordiester bonds. Indirect evidence has suggested
      that the ribozyme's accessory domain binds the NTP with a highly conserved purine
      rich loop. To determine the NTP binding site more precisely we evolved the
      ribozyme for efficient use of 6-thio guanosine triphosphate (6sGTP). 6sGTP never
      appeared in the evolutionary history of the ribozyme, therefore it was expected
      that mutations would appear at the NTP binding site, adapting to more efficient
      binding of 6sGTP. Indeed, the evolution identified three mutations that mediate
      200-fold improved incorporation kinetics for 6sGTP. A >50-fold effect resulted
      from mutation A156U in the purine-rich loop, identifying the NTP binding site.
      This mutation acted weakly cooperative with two other beneficial mutations, C113U
      in the P2 stem near the catalytic site, and C79U on the surface of the catalytic
      domain. The preference pattern of the ribozyme for different NTPs changed when
      position 156 was mutated, confirming a direct contact between position 156 and
      the NTP. The results suggest that A156 stabilizes the NTP in the active site by a
      hydrogen bond to the Hoogsteen face of the NTP.

PMID- 30289488
TI  - Effect of hydrocolloids on the quality of restructured hams with duck skin.
AB  - We investigated the quality of duck ham restructured with various hydrocolloids
      (Alginic acid, Konjac, Carrageenan) on proximate composition, cooking loss,
      emulsion stability, pH, color, texture profile analysis (TPA), protein
      solubility, sensory characteristics, and apparent viscosity. Restructured duck
      ham was prepared as follows: control with no hydrocolloids, T1 (Alginate 1%), T2
      (Alginate 0.5% + Konjac 0.5%), T3 (Alginate 0.7% + Konjac 0.3%), T4 (Alginate
      0.5% + Carrageenan 0.5%), and T5 (Alginate 0.7% + Carrageenan 0.3%). The
      restructured duck hams with hydrocolloids had higher value for moisture content,
      ash content, and apparent viscosity than the control (P < 0.05). The cooking
      loss, total expressible fluid and fat separation, redness, hardness,
      cohesiveness, gumminess, and chewiness of restructured duck hams with
      hydrocolloids was lower than those of the control (P < 0.05). The sensory score
      for overall acceptability of restructured duck ham with T1 (1% alginate) and T2
      (0.5% alginate + 0.5% konjac) was higher than that of the control (P < 0.05).
      Thus, this study showed that adding 1% alginate or 0.5% alginate + 0.5% konjac in
      restructured duck ham formulations results in optimized quality characteristics.

PMID- 30289489
TI  - The Effect of Negative Aging Self-Stereotypes on Satisfaction With Social
      Support.
AB  - Objectives: Previous studies have demonstrated a relationship between negative
      age self-stereotypes and social support satisfaction. This study examined whether
      negative age stereotype plays a causal role, and whether health anxiety is a
      possible mediator, in this relationship. Methods: A total of 114 Chinese older
      persons were randomly assigned into three experimental conditions. In two of the
      conditions, participants were primed with either negative or positive age
      stereotypes using a sentence unscrambling task, before responding to measures of
      self-perception of aging, health anxiety, and satisfaction with family and
      nonfamily support. Those in the control condition responded to the same questions
      without priming. Results: Main effects of priming were found across the board
      except for satisfaction with nonfamily support. In general, participants primed
      with negative age stereotypes reported more negative self-perception of aging,
      higher health anxiety, and lower satisfaction with family support, compared with
      control or those primed with positive age stereotypes. However, the effect on
      family support satisfaction could not be explained by concomitant experimental
      effect on health anxiety. Discussion: The central role of the family as a support
      provider might be the reason why the activation of negative age stereotypes led
      to less satisfaction with family, but not nonfamily.

PMID- 30289490
TI  - EXPOSURE ASSESSMENT OF PORTABLE WIRELESS DEVICES ABOVE 6 GHz.
AB  - The emerging 5 G wireless devices working at frequencies above 6 GHz are expected
      to have antenna arrays formed by dipoles, slots, patches or their combination. At
      lower frequencies, the accepted criteria for exposure compliance is stated in
      terms of specific absorption rate. IEEE and ICNIRP are adopting epithelial or
      transmitted power density (PD through body surface) as the dosimetric reference
      for frequencies above 6 GHz, which entails the measurement of free space PD.
      Theoretical and numerical results presented in this article show that it is
      possible to perform meaningful free space PD assessments at half wave (lambda/2)
      distance from arrays and, with the proper instrumentation, as close as
      lambda/(2pi). However, if a dissipative body is placed very close (<lambda/2pi)
      to the arrays, its reflection and absorption of RF energy can change the electric
      currents and charges over the antenna. The relevance of such an effect should be
      further investigated, for instance by means of experimental analysis including
      measurements of tissue heating when in the presence of a strong reactive near
      field.

PMID- 30289491
TI  - Synergistic effect of phage therapy using a cocktail rather than a single phage
      in the control of severe colibacillosis in quails.
AB  - Infections associated with avian pathogenic Escherichia coli (APEC) cause severe
      economic losses to the poultry industry. The study presented herein investigated
      the in vivo performance of a single phage with prolonged in vivo and in vitro
      survivability alone or in combination with 3 other selected phages in treating
      colibacillosis in quails. Japanese quails (N = 360) were randomly assigned to 6
      treatment groups with 4 replicate pens. Birds from the control groups (groups I,
      II, and III) were treated with 200 MUL sterile PBS (pH 7.4), 200 MUL of the
      selected phage (1010 pfu; TM3) or a cocktail of 4 phages (TM3 plus TM1, TM2, and
      TM4), respectively. Groups IV, V, and VI were challenged with 200 MUL E. coli
      (108 cfu; O78:K80 and O2:K1) and treated with i.m. injection of 200 MUL sterile
      PBS, phage TM3, or cocktail of 4 phages, respectively. Based on the results of
      the present study, the total mortality rate decreased from 46.6% in the untreated
      E. coli-challenged group to 26.5% and 13.6% in the E. coli-challenged group
      treated with single phage or phage cocktail, respectively. The body weights of
      birds treated with the phage cocktail were higher than the body weights of
      untreated birds on days 7, 14, and 21 post-challenge (P < 0.05). In addition,
      total viable cell counts of E. coli in the lungs of birds treated with the phage
      cocktail were lower than those of birds treated with phage TM3 on days 3 and 10
      post-challenge (P < 0.05). Moreover, the incidence and severity of lesions in
      lungs, heart, and liver were found to be significantly less in the E. coli-
      challenged group treated with the phage cocktail. In conclusion, this study
      indicates that a phage cocktail may be more efficient in treating colibacillosis
      than a single phage possibly due to a synergistic effect between the individual
      phages.

PMID- 30289493
TI  - Thioredoxin o-mediated reduction of mitochondrial alternative oxidase in the
      thermogenic skunk cabbage Symplocarpus renifolius.
AB  - Thermogenesis in plants involves significant increases in their cyanide-resistant
      mitochondrial alternative oxidase (AOX) capacity. Because AOX is a non-proton
      motive ubiquinol oxidase, the dramatic drop in free energy between ubiquinol and
      oxygen is dissipated as heat. In the thermogenic skunk cabbage (Symplocarpus
      renifolius), SrAOX is specifically expressed in the florets. Although SrAOX
      harbors conserved cysteine residues, the details of the mechanisms underlying its
      redox regulation are poorly understood. In our present study, the two
      mitochondrial thioredoxin o cDNAs SrTrxo1 and SrTrxo2, were isolated from the
      thermogenic florets of S. renifolius. The deduced amino acid sequences of the
      protein products revealed that SrTrxo2 specifically lacks the region
      corresponding to the alpha3-helix in SrTrxo1. Expression analysis of thermogenic
      and non-thermogenic S. renifolius tissues indicated that the SrTrxo1 and SrAOX
      transcripts are predominantly expressed together in thermogenic florets, whereas
      SrTrxo2 transcripts are almost undetectable in any tissue. Finally, functional in
      vitro analysis of recombinant SrTrxo1 and mitochondrial membrane fractions of
      thermogenic florets indicated its reducing activity on SrAOX proteins. Taken
      together, these results indicate that SrTrxo1 is likely to play a role in the
      redox regulation of SrAOX in S. renifolius thermogenic florets.

PMID- 30289492
TI  - Microvascular Complications of Posttransplant Diabetes Mellitus in Kidney
      Transplant Recipients: a Longitudinal Study Posttransplant Diabetes
      Complications.
AB  - Objective: to assesses microvascular complications in renal transplant recipients
      with posttransplant diabetes mellitus (PTDM). Research Design and Methods: in
      this observational study, patients with >= 5 years of PTDM were included from a
      cohort of 895 kidney recipients transplanted in 2000-2011. Diabetic retinopathy
      was evaluated by fundus photographs and optical coherence tomography (OCT).
      Diabetes kidney disease was evaluated by protein to creatinine ratio (PCR) and
      estimated glomerular filtration rate (eGFR). Distal polyneuropathy was assessed
      by Michigan Protocol and 10 g-monofilament feet exams. The Ewing protocol
      identified cardiovascular autonomic neuropathy. Renal transplant recipients
      without PTDM diagnosis (NPTDM) were considered controls. Results: After 144.5
      months of follow-up, 135 (15%) patients developed PTDM, and 64 had a PTDM
      duration >= 5 years. None of PTDM patients presented diabetic retinopathy at
      fundus photographs but thinning of inner retinal layers was observed with OCT.
      More than 60% of PTDM patients had distal polyneuropathy (OR 1.55; CI 1.26-1.91;
      p<0.001). Cardiovascular reflex tests abnormalities were similar between PTDM and
      NPTDM patients (p=0.26). During the 1st year and after 8.5+/-3.0 years of renal
      transplantation, eGFR and PCR did not differ significantly between patients with
      and without PTDM. Conclusions: This is the first longitudinal study to assess
      microvascular complications in renal PTDM patients. A lower than expected
      prevalence as well as a different clinical course of the complications was
      observed. PTDM seems to be a unique type of diabetes and its consequences may be
      milder than expected in type 1 and type 2 diabetes.

PMID- 30289494
TI  - Race and Objective Social Isolation: Older African Americans, Black Caribbeans,
      and Non-Hispanic Whites.
AB  - Objectives: Social isolation is a major risk factor for poor physical and mental
      health among older adults. This study investigates the correlates of objective
      social isolation among older African Americans, black Caribbean immigrants, and
      non-Hispanic whites. Methods: The analysis is based on the older subsample (n =
      1,439) of the National Survey of American Life. There are eight indicators of
      objective social isolation: no contact with neighbors, neighborhood groups,
      friends, family members, religious congregation members, not being married and no
      romantic involvement, living alone, and not being a parent. Results: Very few
      older Americans are socially isolated from family and friends. Non-Hispanic
      whites are more likely than both African Americans and black Caribbeans to live
      alone, to be childless, and have limited contact with religious congregation
      members. For both African Americans and black Caribbeans, being female is
      protective against social isolation, but for both populations, men are more
      likely to be married or have a romantic partner. For African Americans, residing
      in the South is also protective against social isolation. Discussion: This
      analysis provides greater clarity on racial and ethnic differences in social
      isolation among older adults, as well as within-group differences in objective
      social isolation among African Americans and black Caribbeans.

PMID- 30289495
TI  - THE INVESTIGATION OF MICRONUCLEI FREQUENCY DISTRIBUTION FOR EXPOSED AND UNEXPOSED
      PERSONNEL TO IONIZING RADIATION.
AB  - To establish at which extent the micronuclei (MN) frequency is influenced by
      occupational exposure to ionizing radiation, peripheral blood samples collected
      from 2151 subjects of both genders, smokers and non-smokers were analyzed. Among
      them, 378 (17.6%) were unexposed while the other 1773 (82.4%) were exposed to
      ionizing radiation for periods between 1 year and more than 30 years, at levels
      never overpassing legally regulated limits. The final results showed that for all
      investigated categories, MN frequency monotonously increases with the age by 1.75
      +/- 0.17 times in the case of exposed subjects, but independent on gender and
      smoking habit.

PMID- 30289496
TI  - Ameliorating deleterious effects of heat stress on growing Muscovy ducklings
      using feed withdrawal and cold water.
AB  - We studied the effect of feed withdrawal and cold water on the growth performance
      and health status of 180 Muscovy ducklings (28 days old) during the summer
      season. The experiment used a 3 * 2 factorial design consisting of 3 and 2
      feeding and water systems, respectively. The birds were divided into 6
      experimental groups of 30 birds each (10/replicate). The 3 feeding systems were
      ad libitum, full-feeding (AD); afternoon, feed withdrawn from 8 am to 2 pm daily
      (AF); and diurnal, feed withdrawn from 2 pm to 8 am daily (DI). The 2 water
      systems were tap water (TW) or cold water (CW). The results indicated that the
      different feeding systems with cold water positively affected the growth
      performance, dressed carcass, liver, gizzard, meat tenderness, juiciness,
      susceptibility, body temperature, tonic immobility, and blood biochemistry
      (glucose, aspartate aminotransferase, alanine aminotransferase, total antioxidant
      capacity, and malondialdehyde) of Muscovy ducklings. However, no differences in
      percentages of plumage, leg problems, breast blister scores, and most blood
      parameters were found among all groups. In conclusion, AF feeding of ducklings in
      combination with CW during hot conditions was more suitable than other feeding
      methods.

PMID- 30289497
TI  - Impact of induced anxiety on neural responses to monetary incentives.
AB  - Previous research demonstrates that aversive stimuli can interrupt appetitive
      processing and that brain regions involved with the processing of potential
      rewards, such as the ventral striatum (VS), also respond to threatening
      information. Potential losses can likewise activate the VS and, thus, the full
      extent to which threat can impact neural responses during incentive processing
      remains unclear. Here, unpredictable threat of shock was used to induce anxiety
      while participants performed the monetary incentive delay (MID) task during
      functional magnetic resonance imaging (fMRI). During anticipation, anxiety
      impacted neural responses within the bilateral VS and distributed regions of the
      occipital cortex. Anxiety enhanced activity within the VS to both gain and loss
      trials. Furthermore, anxiety enhanced activity to both gain and loss trials
      within dorsal areas of BA19. However, anxiety only enhanced activity during gain,
      but not loss trials, within ventral areas of BA19. These results suggest that
      during anticipation, induced anxiety enhanced VS activity to incentives
      generally, which might reflect changes in the subjective salience of gains and
      losses. Collectively, these results suggest that the impact of induced anxiety on
      responses to monetary incentives depend on the neural region, type of incentive,
      and stage of processing.

PMID- 30289498
TI  - PATIENT DOSES IN COMMON DIAGNOSTIC X-RAY EXAMINATIONS.
AB  - A local survey was conducted, to evaluate the radiation dose to adult patients
      who underwent diagnostic X-ray examinations. Patient-related and technical data
      were recorded, in 1504 patients, for each of the 11 individual projections, of
      the 7 most common examinations performed in an X-ray room, with 1 digital
      radiography system. The patient entrance surface air kerma (ESAK) and the
      effective dose (ED) were calculated based on the X-ray tube output and the
      exposure parameters, as well as utilisation of suitable conversion coefficients,
      respectively. The 75th percentiles of the distribution of the ESAK and kerma area
      product (KAP) values were also established. The mean, median and 75th percentiles
      were compared with the national reference levels and the most common values
      reported at the European level through the DOSE DATAMED II project. The
      corresponding ED values were also compared with the average values reported for
      all European countries. The mean ESAK, KAP and ED values along with the
      uncertainty U values for chest PA, chest LAT, cranium AP, cranium LAT, cervical
      spine AP, cervical spine LAT, lumbar spine AP, lumbar spine LAT, pelvis AP,
      abdomen AP, kidneys and urinary bladder (KUB) AP were 0.12 (0.001) mGy, 0.66
      (0.023) mGy, 1.01 (0.034) mGy, 0.69 (0.098) mGy, 0.72 (0.014) mGy, 0.63 (0.011)
      mGy, 4.12 (0.050) mGy, 5.74 (0.082) mGy, 2.57 (0.024) mGy, 1.94 (0.017) mGy, 2.47
      (0.073) mGy, and 0.09 (0.001) Gy cm2, 0.38 (0.012) Gy cm2, 0.32 (0.009) Gy cm2,
      0.27 (0.052) Gy cm2, 0.17 (0.004) Gy cm2, 0.21 (0.006) Gy cm2, 1.18 (0.018) Gy
      cm2, 1.86 (0.023) Gy cm2, 1.41 (0.012) Gy cm2, 1.27 (0.010) Gy cm2, 1.28 (0.038)
      Gy cm2, as well as 0.01 (0.0001) mSv, 0.05 (0.0016) mSv, 0.02 (0.0006) mSv, 0.01
      (0.0012) mSv, 0.03 (0.0008) mSv, 0.03 (0.0006) mSv, 0.26 (0.0038) mSv, 0.17
      (0.0022) mSv, 0.20 (0.0016) mSv, 0.23 (0.0018) mSv, 0.23 (0.0068) mSv,
      respectively. The 75th percentiles along with the uncertainty U values for chest
      PA, chest LAT, cranium AP, cranium LAT, cervical spine AP, cervical spine LAT,
      lumbar spine AP, lumbar spine LAT, pelvis AP, abdomen AP, kidneys and urinary
      bladder (KUB) AP were 0.14 (0.006) mGy, 0.88 (0.031) mGy, 1.22 (0.049) mGy, 0.94
      (0.098) mGy, 0.93 (0.027) mGy, 0.78 (0.013) mGy, 5.16 (0.073) mGy, 7.24 (0.134)
      mGy, 2.96 (0.047) mGy, 2.59 (0.036) mGy, 3.07 (0.116) mGy, as well as 0.10
      (0.0006) Gy cm2, 0.51 (0.017) Gy cm2, 0.37 (0.020) Gy cm2, 0.33 (0.040) Gy cm2,
      0.23 (0.007) Gy cm2, 0.26 (0.011) Gy cm2, 1.50 (0.036) Gy cm2, 2.26 (0.035) Gy
      cm2, 1.61 (0.023) Gy cm2, 1.67 (0.017) Gy cm2, 1.56 (0.069) Gy cm2, in terms of
      ESAK and KAP values, respectively. The results were significantly lower compared
      with the national reference levels, the most common DRL values reported at the
      European level and other previously reported dose values. Patient dose surveys
      could contribute towards optimising radiation protection for patients, therefore,
      highlighting the necessity to increase the awareness and knowledge of the
      radiation dose in conjunction with the required image quality.

PMID- 30289499
TI  - A mono-component microbial protease improves performance, net energy, and
      digestibility of amino acids and starch, and upregulates jejunal expression of
      genes responsible for peptide transport in broilers fed corn/wheat-based diets
      supplemented with xylanase and phytase.
AB  - A total of 90 male Ross 308 broiler chicks were used in a digestibility and
      performance bioassay to explore the effect of reduction in dietary protein and
      digestible amino acids and inclusion of an exogenous mono-component protease on
      amino acid digestibility, net energy, jejunal gene expression, and bird
      performance. Four dietary treatments were created by the supplementation, or not,
      of 2 control diets with a mono-component exogenous protease. The control diets
      were corn/wheat/soybean meal-based and were formulated to be either nutritionally
      adequate or reduced in protein and amino acids (around 3%). The 2 control diets
      were supplemented with xylanase and phytase (2000 FYT). Treatments were therefore
      arranged as a 2 * 2 factorial design. The reduction in diet nutrient density had
      no significant effect on various experimental outcomes (including bird
      performance, amino acid digestibility, and net energy [NE]) that were measured
      with the exception of a reduction in the expression of aminopeptidase N and
      glucose transporter 2. However, the addition of exogenous protease resulted in an
      increase in weight gain and a reduction in feed conversion ratio (around 4%; P <
      0.05) and an increase in the digestibility of several amino acids (P < 0.05) and
      starch (P = 0.06). Protease addition also resulted in an increase in both
      apparent metabolizable energy (AME) (+73 kcal/kg; P < 0.05) and NE (+107 kcal/kg;
      P < 0.05). The addition of exogenous protease to the diet also increased the
      jejunal expression of genes responsible for peptide transport (PepT2; P < 0.01)
      and starch digestion (sucrase isomaltase; P = 0.06). These results confirm the
      efficacy of exogenous protease in broiler diets that contain both xylanase and
      phytase and suggest substantial beneficial effects that extend beyond protein and
      amino acid nutrition. The effect of exogenous protease on energy partitioning,
      starch digestibility and the efficiency of nitrogen cycling is an area for
      further study.

PMID- 30289500
TI  - Self-Measured Arm Circumference in Women With Breast Cancer Is Reliable and
      Valid.
AB  - Background: Prospective surveillance by physical therapists enables early
      detection and treatment of breast cancer-related lymphedema (BCRL). Strategies to
      increase access to prospective surveillance could reduce the burden of BCRL on
      patients and the health system. One potential solution is self-managed
      surveillance that does not require in-person assessment by a specialized physical
      therapist. Objective: The objective was to develop and test the reliability and
      validity of a written and video-supported protocol for women with breast cancer
      to self-measure arm circumference. Design: This was a cross-sectional reliability
      and validity study. Methods: Participants with (n = 20) and without (n = 21) BCRL
      completed self-measurement of arm circumference on both arms at home
      (CIRself_home) and at the lab (CIRself_lab) (intrarater reliability). The
      CIRself_lab was subsequently compared to measures performed by a specialized
      physical therapist (CIRther) (interrater reliability). To test validity, arm
      volume calculated from the self-measurements (VOLself_lab) was compared to
      perometry measurements (VOLper). Participants completed a questionnaire to assess
      attitudes for performing self-managed surveillance for BCRL. Results: The
      intrarater reliability between CIRself_home and CIRself_lab and the interrater
      reliability between CIRself_lab and CIRther was high to excellent for both arms
      in both groups (ICC >= 0.86). VOLself_lab correlated strongly with VOLper (r >=
      0.95), demonstrating excellent validity. Participants reported strong intention,
      self-efficacy, and positive attitude towards the performance of self-managed
      surveillance for BCRL, which was not perceived to increase worry about having or
      getting BCRL. Limitations: These findings need to be replicated in a clinical
      setting to confirm the reliability and acceptability of self-managed surveillance
      for BCRL among women newly diagnosed with breast cancer. Conclusions: Self
      measured arm circumference is reliable and valid among women with and without
      BCRL. Self-managed surveillance for BCRL may support self-efficacy without
      increasing anxiety.

PMID- 30289501
TI  - A SCREENING SURVEY EXERCISE FOR THYROID INTERNAL EXPOSURE FROM RADIOIODINE AFTER
      A NUCLEAR ACCIDENT.
AB  - In the aftermath of the 2011 Fukushima nuclear disaster, a screening survey for
      thyroid internal exposure from intake of radioiodine was performed on 1080
      children using handheld NaI(Tl) survey meters. This article presents the design
      and results of a practical exercise conducted to develop the skills of personnel
      who would be potentially engaged in such a survey. Participants of this exercise
      were asked to measure manikin heads in which point sources were installed under
      normal (~0.05 MUSv h-1) and elevated (~0.5 MUSv h-1) background conditions. The
      results demonstrated that the measurements were less dependent on the background
      radiation level, and the deviation of net signals obtained by the participants
      were within 10-20% for dose rates above 0.2 MUSv h-1. This result suggests that
      dose rates can be reliably obtained above a provisional operational intervention
      level for the device, 0.5 MUSv h-1 under a real nuclear accident situation.

PMID- 30289502
TI  - The development of antioxidant system in the intestinal tract of broiler
      chickens.
AB  - The gastrointestinal tract is the site for the uptake of nutrients from the
      external environment. We hypothesized that the antioxidant system in the
      intestinal tract has a vital protective role from the oxidative damage induced by
      oxidants in foods. The aim of this study was to investigate the development of
      the antioxidant system in the intestine of chickens. The activity and gene
      expression of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT),
      and glutathione peroxidase (GSH-Px) and the content of the non-enzymatic
      substance glutathione (GSH) were measured in the duodenum, jejunum, and ileum of
      chickens at 1, 3, 7, 11, 14, 21, 35, and 42 d of age. The results showed that the
      small intestinal tract had relatively higher SOD activity and GSH concentration
      and lower CAT and GSH-Px activities, compared with those of other visceral
      organs. CAT and GSH-Px activities and GSH concentration showed a decreasing trend
      with age, whereas SOD activity was not significantly influenced by age. The gene
      expression of SOD1, SOD2, and GSH-Px7 showed a dramatic decrease from 3 d of age.
      The results indicated that SOD and GSH were highly expressed in the first week of
      age after hatching. To conclude, the results suggest that SOD and GSH play a
      vital protective role in the small intestine after hatching, which contributes to
      rapid development of the intestine.

PMID- 30289504
TI  - Phenotypic and Genotypic Plasticity of Acaricide Resistance in Populations of
      Tetranychus urticae (Acari: Tetranychidae) on Peppermint and Silage Corn in the
      Pacific Northwest.
AB  - Tetranychus urticae Koch is a generalist pest of economic crops and is notorious
      for its rapid development of acaricide resistance. This poses a significant
      threat to the sustainability of integrated pest management (IPM) in cropping
      systems plagued by T. urticae. It is critical to evaluate the resistance status
      of T. urticae populations on crops and identify any underlying resistance
      mechanisms. This study investigated the efficacy of five major acaricides on T.
      urticae populations on peppermint and silage corn in the Pacific Northwestern
      United States and identified the underlying resistance mechanisms. Significant
      variations in acaricide resistance status of T. urticae populations were
      identified to abamectin, bifenthrin, fenpyroximate, hexythiazox, and
      spirodiclofen. In most cases, T. urticae populations from silage corn exhibited
      greater levels of acaricide resistance relative to peppermint populations. We
      detected known target-site mutations: F1534S and F1538I (conferring resistance to
      bifenthrin), G126S (linked with resistance to bifenazate), and I1017 (conferring
      resistance to hexythiazox and etoxazole) in 10, 90, and 90% of the populations,
      respectively, from peppermint fields. These four mutations were identified in all
      the populations collected from silage corn fields. Significantly higher
      transcript levels of metabolic genes associated with resistance to abamectin,
      fenpyroximate, and spirodiclofen were observed in some T. urticae populations
      collected from both peppermint and silage corn fields. This study provides
      evidence of multiple resistance to diverse active ingredients in field
      populations of T. urticae and the reliability of known molecular markers for
      active acaricide resistance monitoring. The observed resistance pattern will help
      in designing a sustainable IPM program for T. urticae.

PMID- 30289503
TI  - NATURAL RADIOACTIVITY AND EVALUATION OF RADIATION HAZARDS IN SOILS FROM
      GRANITOIDE-GRANITE GEOLOGICAL FORMATION IN CUBA.
AB  - The natural radioactivity and the associated radiation hazards of soils from the
      Cumanayagua Granitoide-Granitic massif in the central south of Cuba have been
      studied. Mass activities of the natural radionuclides 238U, 232Th and 40K varied
      in the ranges 10.4-33, 4.6-21.7 and 381-1201 Bq kg-1, respectively. The radium
      equivalent activity (91.4 +/- 22.1 Bq kg-1), absorbed dose rate (45.6 +/- 11.1
      nGy h-1), annual effective dose rate (56.1 +/- 13.7 MUSv y-1) and the external
      hazard index (0.25 +/- 0.06) have been calculated and compared with the
      internationally approved values. According to these results, the area can be
      regarded as an area with normal natural background radiation and may not pose
      radiological risks to the inhabitants owing to harmful effects of ionizing
      radiation from the natural radionuclides in soils. This study provides background
      radioactivity concentrations in Cumanayagua Granitoide area and generate a
      baseline data for radiological mapping of Cuba in the future.

PMID- 30289505
TI  - Selection of Reference Genes for Optimal Normalization of Quantitative Real-Time
      Polymerase Chain Reaction Results for Diaphorina citri Adults.
AB  - The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae), can
      cause direct damage to citrus trees and is the main vector for the devastating
      disease, citrus greening disease or huanglongbing. Most molecular studies on this
      important insect pest use real-time reverse-transcription quantitative polymerase
      chain reaction (RT-qPCR) to quantify gene expression, including analyzing
      molecular basis for insecticide resistance in field populations. One critical
      factor to cause inaccuracy in RT-qPCR results is the lack of appropriate internal
      reference genes for optimal data normalization. In this study, the expression
      levels of 10 selected reference genes were evaluated in different tissue samples
      of psyllid adults and in the insects treated with different temperatures and
      insecticides. Data were analyzed using different computational algorithms,
      including Delta Ct, BestKeeper, NormFinder, geNorm, and RefFinder. According to
      our results, at least two reference genes should be used for the normalization of
      RT-qPCR data in this insect. The best choices of reference genes for different
      samples are as follows: ACT1 and Ferritin for different tissue samples, RPS20 and
      Ferritin for samples treated with different temperatures, TBP and EF1alpha for
      samples treated with imidacloprid, and Ferritin and TBP for samples treated with
      beta-cypermethrin. The reference genes identified in this study should be useful
      for future studies to analyze the expression patterns of target genes, especially
      for genes linked with temperature adaptability and insecticide resistance in this
      insect species in the future.

PMID- 30289506
TI  - Disruption of Phosphatidylserine Synthesis or Trafficking Reduces Infectivity of
      Ebola Virus.
AB  - The outer leaflet of the viral membrane of Ebola virus (EBOV) virions is enriched
      with phosphatidylserine (PtdSer), which is thought to play a central role in
      viral tropism, entry, and virus-associated immune evasion. We investigated the
      effects of inhibiting synthesis and/or export of PtdSer to the cell surface of
      infected cells on viral infectivity. Knockdown of both PtdSer synthase enzymes,
      PTDSS1 and PTDSS2, effectively decreased viral production. Decreased PtdSer
      expression resulted in an accumulation of virions at the plasma membrane and
      adjacent of intracellular organelles, suggesting that virion budding is impaired.
      The addition of inhibitors that block normal cellular trafficking of PtdSer to
      the plasma membrane resulted in a similar accumulation of virions and reduced
      viral replication. These findings demonstrate that plasma membrane-associated
      PtdSer is required for efficient EBOV budding, increasing EBOV infectivity, and
      could constitute a potential therapeutic target for the development of future
      countermeasures against EBOV.

PMID- 30289507
TI  - Healthy Post-Menarchal Adolescent Girls Demonstrate Multi-Level Reproductive Axis
      Immaturity.
AB  - Context: Menstrual irregularity after menarche has been attributed to immature
      estrogen positive feedback activity (E+FB) but data are conflicting. Objective:
      To determine the hypothalamic-pituitary-ovarian contributions to menstrual
      irregularity in adolescents. Methods: 23 healthy girls (aged 12.8-17.6 years, 0.4
      3.5 years post-menarche, BMI [body mass index] percentile 41.0-99.3) underwent
      serial hormone measurements and pelvic ultrasounds during 2 consecutive menstrual
      cycles. Hormones and follicle growth were compared with 65 adult historic
      controls with ovulatory cycles (OV). Results: Girls had anovulatory cycles (ANOV;
      30%), OV with a short luteal phase (short OV; 22%), or OV with normal luteal
      phase (normal OV; 48%) without differences in cycle length, chronologic or
      gynecologic age, or BMI. Adolescents showed a spectrum of E+FB (mid-cycle LH
      adjusted for pre-ovulatory estradiol [E2]); only normal OV girls were comparable
      to adults. All OV girls had lower E2, progesterone, and gonadotropins during the
      luteal phase and luteal-follicular transition compared with adults. Normal OV
      girls also had lower follicular phase LH and FSH levels, a longer follicular
      phase, a slower dominant follicle growth rate, and smaller estimated pre
      ovulatory follicle size than adults. Follicular phase E2 and INHB levels were
      lower in normal OV girls than in adults even after adjusting for differences in
      FSH and follicle size. Conclusions: Early post-menarchal girls with normal OV
      cycles demonstrate mature E+FB but continue to have lower gonadotropin levels,
      diminished ovarian responsiveness, and decreased corpus luteum sex steroid
      synthesis compared with adults, indicating that reproductive axis maturity
      requires coordinated development of all components of the hypothalamic-pituitary
      ovarian axis.

PMID- 30289508
TI  - The linc00152 Controls Cell Cycle Progression by Regulating CCND1 in 16HBE Cells
      Malignantly Transformed by Cigarette Smoke Extract.
AB  - Smoking is one of the major environmental risk factors for lung cancer. In recent
      years, the role of long-chain non-coding RNAs (lncRNA) in chemical carcinogenesis
      has attracted extensive research attention. In this study, we treated human
      bronchial epithelial cells with cigarette smoke extract (CSE) at a dose of 2
      MUg/mL to establish a malignantly transformed cellular model (16HBE-M). Screening
      of lncRNAs highly expressed in transformed cells via differential analysis
      revealed a crucial role of linc00152 in CSE-induced malignant transformation. The
      linc00152 serum level in cigarette smoke extract-exposed individuals was
      increased in a dose-dependent manner and its high expression associated with
      metastasis and proliferation of lung cancer tissue. In malignantly transformed
      16HBE-M cells, linc00152 was involved in regulation of cell adhesion, epithelial
      transition and other malignant phenotypes, which in turn, affected in vivo
      metastasis. Interference with linc00152 expression led to G1/S arrest and
      inhibition of proliferation of 16HBE-M and H1299 cells. Furthermore, linc00152
      promoted cyclin D1 expression and G1/S transition by functioning as an endogenous
      competitive RNA targeting miR-193b. Our collective findings supported a critical
      regulatory role of linc00152 in cell cycle alterations and abnormal proliferation
      in CSE-induced malignant transformation of human bronchial epithelial cells.

PMID- 30289509
TI  - RADIATION DOSE TO PATIENTS IN CORONARY INTERVENTIONAL PROCEDURES: A SURVEY.
AB  - The objective of this study was to evaluate dose-area product (DAP) and peak skin
      dose (PSD) for coronary angiography (CA) and percutaneous coronary intervention
      (PCI). The DAP and PSD of 300 randomly selected patients who were referred to CA
      and/or PCI, over a period of 3 months were recorded and analyzed. The mean DAP of
      32 Gy cm2 and mean PSD of 412 mGy for CA were lower than 118 Gy cm2 and 857 mGy,
      respectively, for PCI. The DAP range of 2-84 Gy cm2 for CA and 12-378 mGy for PCI
      were also established. The maximum value of PSD for PCI procedures reached above
      the 2 Gy threshold for erythema. However, these values are similar to those
      available in literature. Periodic surveys may be required to monitor and/or
      reduce radiation doses in coronary interventional procedures.

PMID- 30289510
TI  - Dual practice of public hospital physicians in Vietnam.
AB  - Although many public hospital physicians in Vietnam offer private service on the
      side, little is known about the magnitude and nature of the phenomenon so-called
      dual practice, let alone the dynamics between the public and private health
      sectors. This study investigates how and to what degree public hospital
      physicians engage in private practice. It also examines the commitment of dual
      practitioners to the public sector. The analysis is based on a hospital-based
      survey of 483 physicians at 10 public hospitals in four provinces of Vietnam.
      Nearly half of the participants in the study sample reported themselves as dual
      practitioners. Various types of private practice were mentioned. Private practice
      at health facilities owned by the private sector was the most prevalent, followed
      by private practice delivered at health facilities owned by the dual
      practitioners themselves. Private practice inside public hospitals was also
      noted. Dual practitioners were likely to be senior and hold management positions
      inside their public hospitals. Substantial income differences were found between
      dual practitioners and those physicians practicing exclusively in the public
      sector. The majority of dual practitioners, however, reported the willingness to
      give up private practice if certain conditions were met, such as a basic salary
      increase or non-pecuniary benefits. The main reasons dual practitioners gave for
      not leaving the public sector included a sense of public responsibility and
      opportunities to gain a broader professional network and more training. This
      study reiterates the significant challenges associated with dual practice,
      including its financial implications and possible effects on health care quality
      and access. The need for a high-quality workforce committed to the public sector
      is particularly critical, given the possibility of universal insurance coverage.
      Future research should address the need to improve data collection on physicians'
      dual practice and incorporate the topic in policy debates on health reform.

PMID- 30289511
TI  - The impact of ASEAN economic integration on health worker mobility: a scoping
      review of the literature.
AB  - The Association of Southeast Asian Nations (ASEAN) Economic Community (AEC) was
      inaugurated in December 2015 with the primary aim of achieving a strong and
      prosperous community through accelerating economic integration. The notion of a
      single market, underpinned by the free flow of trade in services and skilled
      labour, is integral to the spirit of the AEC. To facilitate the intra-regional
      mobility of health professionals, Mutual Recognition Arrangements (MRAs) were
      signed, for nursing in 2006 and for medicine and dentistry in 2009, and now sit
      within the AEC objectives. This study examines the observed and potential impact
      of the health-related MRAs on health worker mobility within the region,
      particularly with regard to qualified doctors and nurses. To explore the
      available evidence, the authors undertook a narrative literature and document
      review, consistent with the RAMESES guidelines for qualitative research in
      international development and policy making in the area of health. Peer-reviewed
      articles and the grey literature from the period beginning in 2005 were reviewed.
      We find that the implementation of health-related MRAs has been slow and complex
      due to a number of barriers and challenges, such as resistance to the inflow of
      health professionals by the local workforce, shortcomings in the implementing
      mechanisms and an individual preference among health professionals for seeking
      better opportunities outside the region. Despite increasing worker mobility
      generally within ASEAN through formal and informal mechanisms, the MRAs
      themselves do not appear yet to have facilitated the freer movement of health
      workers. To strengthen health worker mobility, the full implementation of the
      health-related MRAs is essential, requiring support from broader trade and
      immigration policies and a stronger political commitment. Policy makers in ASEAN
      Member States will need to manage competing national interests in order to
      harness support for effective implementation.

PMID- 30289513
TI  - Quality of low-fat chicken sausages with added chicken feet collagen.
AB  - The present study aimed to replace the fat in cooked chicken sausages with
      commercial hydrolyzed collagen powder and chicken feet gelatin and to assess the
      qualities underlying physicochemical and sensory parameters. Three sausages were
      prepared: SS (15% fat), SC (7.5% fat and 7.5% hydrolyzed collagen powder), and SG
      (7.5% fat and 7.5% chicken feet collagen). The reduction of fat increased the
      values of a*, b*, and Hue. With regard to emulsion stability, SG had the closest
      value (95.86%) to the standard (SS) value and was more stable than the SC sausage
      (87.33%). With regard to texture profile, the SC sausage had similar parameters
      to SS, and the SG sample had lower adhesiveness, gumminess, and chewiness. With
      regard to fatty acid profile, SG had the lowest atherogenic and thrombogenic
      indices. The use of 50% gelatin was viable because it increased emulsion
      stability and water retention, in addition to using byproduct to prepare
      healthier sausages, especially regarding fat reduction.

PMID- 30289512
TI  - Dietary deoxynivalenol and oral lipopolysaccharide challenge differently affect
      intestinal innate immune response and barrier function in broiler chickens.
AB  - Dietary deoxynivalenol (DON) impairs the intestinal immune system and digestive
      functions of broiler chickens. However, little is known whether increasing doses
      of DON similarly affect the intestinal functions in different segments of the
      small intestine in chickens and whether a second oral challenge may potentiate
      those effects. The present objective was to investigate the effect of increasing
      dietary DON concentrations on the relative expression of genes for tight junction
      proteins, mucins, toll-like receptors (TLR), and cytokines in duodenum and
      jejunum, jejunal mucosal permeability, as well as on alpha-1-acid glycoprotein
      and IgA in serum with or without an additional oral lipopolysaccharide (LPS)
      challenge. Eighty 1-d-old chickens were fed diets with increasing DON
      concentrations (0, 2.5, 5, and 10 mg DON/kg diet) for 5 wk. One day before
      sampling, half of the chickens received an oral challenge with 1-mg Escherichia
      coli O55:B5 LPS/kg BW. Ussing chambers were used to measure the jejunal
      permeability in birds receiving 10-mg DON/kg feed with or without LPS challenge
      and 0-mg DON/kg feed without LPS. Increasing DON concentrations of up to 5-mg
      DON/kg increased (P < 0.05) the duodenal expression of TLR2, IL6, and Claudin 1
      (CLDN1) by up to 84%, 88%, and 48%, respectively, compared with the
      noncontaminated diet. Likewise, jejunal CLDN1 expression increased up to 23% in
      the chickens fed DON concentrations of up to 5-mg DON/kg diet (P < 0.05).
      Moreover, increasing DON concentrations linearly and quadratically decreased (P <
      0.05) the jejunal expression of TLR2 and transforming growth factor-beta 1,
      respectively. The additional LPS challenge increased (P < 0.040) duodenal
      occludin expression by 10% as well as the jejunal tissue conductance in chickens
      of the 10 DON group (P = 0.050). In conclusion, dietary DON differently affected
      the duodenal and jejunal expression of genes for tight-junction proteins and
      proinflammatory signaling pathways. The additional LPS challenge did not
      potentiate the DON effect but it seemed to induce a certain up-regulation of the
      proinflammatory response in the duodenum and enhanced the mucosal permeability in
      the jejunum.

PMID- 30289514
TI  - The Tehran Heart Center.

PMID- 30289515
TI  - The Journal of Tehran University Heart Center.

PMID- 30289516
TI  - Cardiology services in Ethiopia.

PMID- 30289518
TI  - EHJ International Associate Editor.

PMID- 30289517
TI  - Weekend effect on Acute MI mortality.

PMID- 30289520
TI  - New Head of Cardiology, Liege University, Belgium.

PMID- 30289519
TI  - Chest compression for syncope in medieval Persia.

PMID- 30289521
TI  - Improving outcomes after acute coronary events: what works and what doesn't.

PMID- 30289523
TI  - Ultrasound-Guided Plantar Fascia Injections: Where Are You Putting the Gas or
      Steroids?

PMID- 30289524
TI  - For Smoking Cessation, E-Cigarette Flavors Aren't Required.

PMID- 30289525
TI  - Feeding and lighting practices on small-scale extensive pastured poultry
      commercial farms in the united states.
AB  - As commercial free-range and pastured poultry production has gained increased
      popularity in the United States in recent years, there is a greater need to
      understand basic husbandry practices including feeding and lighting practices.
      Because husbandry practices vary greatly between individual commercial pastured
      poultry and free-range operations, gaining knowledge across a wide cross-section
      of producers is necessary to better understand current practices. Specifically,
      because feed is considered the most expensive part of poultry production with
      respect to operating cost, in collaboration with the American Pastured Poultry
      Producers Association, an on-line survey of commercial free-range and pastured
      poultry producers was conducted aimed primarily at evaluating feeding and
      lighting practices. Data were collected from 14 commercial pastured (n = 13) and
      free-range (n = 1) producers (6 broiler, 1 layer, and 7 broiler/layer facilities)
      across 9 U.S. states. Results showed that these operations most commonly use
      Cornish Cross for broiler production and ISA Brown and Australorp for egg
      production. Only 1 of the 14 farms calculates feed conversion ratio on a monthly
      basis. Estimates of Hen Month Egg Production (HMEP) resulted in HMEP percentages
      that were over 100% in 6 of the 7 farms that provided data. 5 of the 7 farms that
      have layers used supplemental lighting but do not use a lux meter. These lack of
      data reflect an important challenge with this segment of the poultry industry.
      Extension based outreach focused on enabling data collection and record-keeping
      and analysis are necessary. Despite its small sample size, this study's results
      provide some valuable insights with respect to feeding equipment and the current
      state of data collection for this segment of the poultry industry.

PMID- 30289522
TI  - Natural Disease Course of Ulcerative Colitis During the First Five Years of
      Follow-up in a European Population-based Inception Cohort-An Epi-IBD Study.
AB  - Background and Aims: Few population-based cohort studies have assessed the
      disease course of ulcerative colitis [UC] in the era of biological therapy and
      widespread use of immunomodulators. The aim of this study was to assess the 5
      year outcome and disease course of patients with UC in the Epi-IBD cohort.
      Methods: In a prospective, population-based inception cohort of unselected
      patients with UC, patients were followed up from the time of their diagnosis,
      which included the collection of their clinical data, demographics, disease
      activity, medical therapy, and rates of surgery, cancers, and deaths.
      Associations between outcomes and multiple covariates were analysed by Cox
      regression analysis. Results: A total of 717 patients were included in the study.
      During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients
      were hospitalised. Of patients with limited colitis [distal to the left flexure],
      90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with
      extensive colitis experienced a regression in disease extent, which was
      associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI:
      0.3-0.8]. Overall, patients were treated similarly in both geographical regions;
      80 [11%] patients needed biological therapy and 210 [29%] patients received
      immunomodulators. Treatment with immunomodulators was found to reduce the risk of
      hospitalisation [HR: 0.5 95% CI: 0.3-0.8]. Conclusions: Although patients in this
      population-based cohort were treated more aggressively with immunomodulators and
      biological therapy than in cohorts from the previous two decades, their disease
      outcomes, including colectomy rates, were no different. However, treatment with
      immunomodulators was found to reduce the risk of hospitalisation.

PMID- 30289526
TI  - West Nile in Europe: an increasing public health problem.

PMID- 30289527
TI  - Comparative effects of in ovo versus subcutaneous administration of the Marek's
      disease vaccine and pre-placement holding time on the intestinal villus to crypt
      ratios of Ross 708 broilers during early post-hatch development,.
AB  - Villus to crypt ratio (VCR) is used to quantify the microanatomical response of
      the intestine to various treatments. In early age chickens, comparative effects
      of the in ovo (i.o.) and s.c. methods of administration (moa) of the Marek's
      disease (MD) vaccine on 2 types of measurement of small intestinal VCR at 0 and 4
      h post-hatch (poh) were investigated. The effects of moa and 4 and 18 h pre
      placement holding times (pht) on the VCR measurements at 168 h (7 d) poh were
      also investigated. In the jejunum of the small intestine, a standard method for
      VCR determination, based on 10 villus and crypt length measurements, was utilized
      for the calculation of villus to crypt length ratio (VCLR). In that same region,
      a single histomorphometric determination of the crypt and total mucosa areas
      using image analysis software was also used. Subtraction of the crypt area from
      the total mucosa area provided the villus area, allowing for calculation of the
      villus to crypt area ratio (VCAR). Across 0, 4, and 18 h of poh bird age, the
      VCLR of birds that received an s.c. vaccination was higher in comparison to that
      of those that received an i.o. vaccination. The highest and lowest VCAR values
      were observed in the s.c. treatment at 0 h poh and in the i.o. treatment at 4 h
      poh, respectively. Furthermore, at 168 h poh, VCLR values in the 18 h pht and
      s.c. vaccination group were higher than those in the 4 h pht and s.c. vaccination
      or 18 h and i.o. vaccination groups. In conclusion, the effects of pht and MD
      vaccine moa on VCR were dependent on the use of either the VCLR or VCAR method of
      measurement. However, regardless of method, s.c. injection overall led to a
      higher VCR through 4 h poh in Ross 708 broilers, and the effects of moa on VCLR
      at 168 h were influenced by pht.

PMID- 30289529
TI  - Specific mutations in presenilin 1 cause conformational changes in gamma
      secretase to modulate amyloid beta trimming.
AB  - gamma-Secretase generates amyloid beta peptides (Abeta) from amyloid precursor
      protein (APP) through multistep cleavages, such as endoproteolysis (epsilon
      cleavage) and trimming (gamma-cleavage). Familial Alzheimer's disease (FAD)
      mutations within the catalytic subunit protein of presenilin 1 (PS1) decrease
      gamma-cleavage, resulting in the generation of toxic, long Abetas. Reducing long
      Abeta levels has been proposed as an AD therapeutic strategy. Previously, we
      identified PS1 mutations that are active in the absence of nicastrin (NCT) using
      a yeast gamma-secretase assay. Here, we analyzed these PS1 mutations in the
      presence of NCT, and found that they were constitutively active in yeast. One
      triple, 13 double, and five single mutants enhanced epsilon-cleavage activity up
      to 2.7-fold. Furthermore, L241I, F411Y, S438P, and F441L mutations modulated
      trimming activities to produce more short-Abeta in yeast microsomes. When
      introduced in mouse embryonic fibroblasts, these mutations possessed similar or
      reduced epsilon-cleavage activity. However, two mutations, L241I and S438P,
      modulated trimming activities and changed the conformation of transmembrane
      domain 1, the substrate recognition site. These mutants had the opposite
      modulatory effects of FAD mutations and produced more short Abetas and fewer long
      Abetas. Our results provide insights into the relationship between PS1
      conformational changes and gamma-secretase activities.

PMID- 30289528
TI  - IMG/M v.5.0: an integrated data management and comparative analysis system for
      microbial genomes and microbiomes.
AB  - The Integrated Microbial Genomes & Microbiomes system v.5.0 (IMG/M:
      https://img.jgi.doe.gov/m/) contains annotated datasets categorized into:
      archaea, bacteria, eukarya, plasmids, viruses, genome fragments, metagenomes,
      cell enrichments, single particle sorts, and metatranscriptomes. Source datasets
      include those generated by the DOE's Joint Genome Institute (JGI), submitted by
      external scientists, or collected from public sequence data archives such as
      NCBI. All submissions are typically processed through the IMG annotation pipeline
      and then loaded into the IMG data warehouse. IMG's web user interface provides a
      variety of analytical and visualization tools for comparative analysis of isolate
      genomes and metagenomes in IMG. IMG/M allows open access to all public genomes in
      the IMG data warehouse, while its expert review (ER) system (IMG/MER:
      https://img.jgi.doe.gov/mer/) allows registered users to access their private
      genomes and to store their private datasets in workspace for sharing and for
      further analysis. IMG/M data content has grown by 60% since the last report
      published in the 2017 NAR Database Issue. IMG/M v.5.0 has a new and more powerful
      genome search feature, new statistical tools, and supports metagenome binning.

PMID- 30289530
TI  - Validation of in vitro digestion using simulated small intestinal fluid with
      specific digestive activity to predict the metabolizable energy of feed
      ingredients for duck.
AB  - Two experiments were conducted to validate a method to prepare simulated small
      intestinal fluid (SSIF) for in vitro digestion in ducks. Experiment 1 compared
      the in vitro digestible energy (IVDE) of SSIF to endogenous small intestinal
      fluid (ESIF) on four feeds. The ESIF 1 or 2 obtained from two groups of jejunal
      cannulated ducks offered diet 1 (3,050 kcal/kg of ME and 19.95% of CP) or 2
      (2,801 kcal/kg of ME and 14.90% of CP) was purified into raw enzyme power (REP) 1
      or 2. SSIF 1 to 3 or 4 to 6 were prepared to mimic ESIF 1 or 2, respectively. The
      enzyme sources were REP 1 for SSIF 1 and 4, REP 2 for SSIF 2 and 5 or reagent
      enzymes for SSIF 3 and 6, respectively. The IVDE of each feed was determined with
      SSIF or ESIF. Experiment 2 was to validate whether REP 1 was more effective than
      only reagent enzymes to prepare SSIF. Ten feeds were determined with pepsin
      following SSIF 1 or 3 for IVDE 1 or 2, respectively. The accuracy of prediction
      model of true metabolizable energy (TME) from IVDE 1 or 2 was evaluated to
      validate the efficacy of SSIF. In experiment 1, higher activities of amylase,
      trypsin and chymotrypsin were observed in ESIF 1 than ESIF 2 (P < 0.05). The IVDE
      determined with SSIF 1 and 2 or 3 and 4 were more comparable to that of ESIF 1 or
      2 than determinations with SSIF 3 or 6. In experiment 2, the mean IVDE 1 or 2 was
      97.22% or 96.23% relative to TME, respectively, and both were highly correlated
      with TME (P < 0.01; R2 >= 0.98). However, the residual SD of TME prediction model
      with IVDE 1 was less than that generated with IVDE 2 (55 vs. 71 kcal/kg). In
      conclusion, the IVDE determined with in vitro digestion of pepsin following SSIF
      prepared with REP can predict accurately TME of feed for ducks.

PMID- 30289532
TI  - The arogenate dehydratase ADT2 is essential for seed development in Arabidopsis.
AB  - Phenylalanine (Phe) biosynthesis in plants is a key process, as Phe serves as
      precursor of proteins and phenylpropanoids. The prephenate pathway connects
      chorismate, final product of the shikimate pathway, with the biosynthesis of Phe
      and Tyr. Two alternative routes of Phe biosynthesis have been reported: one
      depending on arogenate, and the other on phenylpyruvate. Whereas the arogenate
      pathway is considered the main route, the role of the phenylpyruvate pathway
      remains unclear. Here, we report that the deficiency in ADT2, a bifunctional
      arogenate dehydratase (ADT)/ prephenate dehydratase (PDT) enzyme, causes embryo
      arrest and seed abortion. This result makes a clear distinction between the
      essential role of ADT2 and the five remaining ADTs from Arabidopsis, which
      display mostly overlapping functions. We have found that PHA2, a monofunctional
      PDT from yeast, restores the adt2 phenotype when it is targeted within the
      plastids, but not when is expressed in the cytosol. Similar results can be
      obtained by expressing ADT3, a monofunctional ADT. These results suggest that Phe
      can be synthesized from phenylpyruvate or arogenate when the bifunctional ADT2 is
      replaced by other ADT or PDT enzymes during seed formation, highlighting the
      importance of Phe biosynthesis for embryo development, and providing further
      insights into the plasticity of Phe biosynthesis.

PMID- 30289533
TI  - In vitro assessment of antifungal, antibacterial, and antiprotozoal drugs against
      clinical isolates of Conidiobolus lamprauges.
AB  - We have determined the in vitro activity of antifungal, antibacterial, and
      antiprotozoal drugs alone and in combination against seven Conidiobolus
      lamprauges clinical isolates. The assays were based on the M38-A2 protocol and
      the checkerboard microdilution method. The lowest inhibitory concentrations were
      observed for amphotericin B, miconazole (MCZ), terbinafine, and miltefosine (MTF)
      (MIC range 0.25-1; 2-8; 0.25-2; 2-16 MUg/ml, respectively). The main synergism
      observed was through the combination of azithromycin (AZI)+MTF and dapsone
      (DAP)+MTF (100%), AZI+DAP (85.7%), AZI+MCZ (57.1%) as well as MCZ plus CTX and
      DAP (42.9%). The in vitro activities suggest that the combination of MTF and AZI
      or DAP are promising candidate therapies for conidiobolomycosis.

PMID- 30289531
TI  - Role of Transmembrane Protein 16F in the Incorporation of Phosphatidylserine Into
      Budding Ebola Virus Virions.
AB  - Viral apoptotic mimicry, which is defined by exposure of phosphatidylserine
      (PtdSer) into the outer leaflet of budding enveloped viruses, increases viral
      tropism, infectivity and promotes immune evasion. Here, we report that the
      calcium (Ca2+)-dependent scramblase, transmembrane protein 16F (TMEM16F), is
      responsible for the incorporation of PtdSer into virion membranes during Ebola
      virus infection. Infection of Huh7 cells with Ebola virus resulted in a
      pronounced increase in plasma membrane-associated PtdSer, which was demonstrated
      to be dependent on TMEM16F function. Analysis of virions using imaging flow
      cytometry revealed that short hairpin RNA-mediated down-regulation of TMEM16F
      function directly reduced virion-associated PtdSer. Taken together, these studies
      demonstrate that TMEM16F is a central cellular factor in the exposure of PtdSer
      in the outer leaflet of viral membranes.

PMID- 30289534
TI  - Randomized controlled trials and real-world data: differences and similarities to
      untangle literature data.
AB  - Randomized controlled trials (RCTs) represent the gold-standard of medical
      evidence to assess the efficacy and safety of therapeutic interventions. However,
      the need to minimize bias and ensure the correct design to explore the study aims
      often affects the generalizability of results. As a consequence, the evidence
      derived from the most rigorous research strategy available is not always
      representative of the real-world settings for which this evidence is ultimately
      intended. Observational studies, in contrast, although affected by a number of
      potential confounders, can more effectively capture treatment characteristics and
      safety issues that had not been identified by previous RCTs, owing to the short
      duration of follow-up or highly selective inclusion criteria. The aim of this
      review is to provide a comparative summary of the main advantages and pitfalls of
      RCTs and real-world data, emphasizing the need for a constant integration of all
      available levels of evidence to provide the best care for patients.

PMID- 30289535
TI  - 20 years of experience with tumour necrosis factor inhibitors: what have we
      learned?
AB  - TNF inhibitors are biologic DMARDs approved for the treatment of active RA in mid
      1990s. They still represent a valuable therapeutic option to control the
      activity, disability and radiographic progression of the disease. In the context
      of TNF inhibitors, there are currently several molecules and different
      administration routes that provide optimal treatment personalization, allowing us
      to respond to a patient's needs in the best possible way. The increasing use of
      TNF inhibitors has not only improved the management of RA, but it has also helped
      in our understanding of the pathogenetic mechanisms of the disease. This review
      focuses on the basis of this targeted therapy and on the knowledge gained from
      their use about therapeutic effects and adverse events. Effectiveness analysed
      from drug registries and safety issues are presented together with recent data on
      infections (in particular, Mycobacterium tuberculosis and hepatitis B), cancer
      (lymphoma, skin cancers) and cardiovascular risk.

PMID- 30289536
TI  - Tailored approach to rheumatoid arthritis treatment with TNF inhibitors: where do
      we stand?

PMID- 30289537
TI  - The influence of comorbidities on the efficacy of tumour necrosis factor
      inhibitors, and the effect of tumour necrosis factor inhibitors on comorbidities
      in rheumatoid arthritis: report from a National Consensus Conference.
AB  - Objective: To define the safety and efficacy of TNF inhibitors (TNFi) in RA
      patients with comorbidities. Methods: A National Consensus Conference adopted a
      five-step process to better address the place of TNFi in the treatment of RA.
      Here we report the work focused on the influence of comorbidities on TNFi
      efficacy and the effect of TNFi on comorbidities using a Population Intervention
      Comparison Outcome-based strategy from 8 April 2013 to 15 January 2016. Results:
      A total of 4453 hits were analysed, of which 10 were eligible for full review.
      Data show that the presence of comorbidities influences the treatment strategy
      and several clinical outcomes. The risk of solid cancer is similar in RA patients
      treated with TNFi or with conventional synthetic DMARDs, and the risk of
      recurrent breast cancer is not higher in RA patients treated with TNFi. The risk
      of developing serious infections is higher in RA patients receiving TNFi than
      conventional synthetic DMARDs. Patients with previous serious infections before
      starting TNFi are not at increased risk of subsequent serious infection. The
      hazard rate of hospitalization due to infections is not different among patients
      remaining on the same TNFi, or switching to a different TNFi or to an agent with
      another mechanism of action. Longer exposure to TNFi is associated with a
      reduction in the risk of cardiovascular events. Conclusion: Comorbidities affect
      RA treatment strategies and the efficacy of TNFi. TNFi treatment may decrease the
      risk of cardiovascular diseases and their use in patients with previous infection
      is not associated with a higher risk of recurrences.

PMID- 30289538
TI  - Immediate treatment with tumour necrosis factor inhibitors in synthetic disease
      modifying anti-rheumatic drugs-naive patients with rheumatoid arthritis: results
      of a modified Italian Expert Consensus.
AB  - Objective: To establish clinical consensus for the optimal placement of TNF
      inhibitor (TNFi) in DMARDs-naive RA patients. Methods: The steering group was
      composed of 15 Italian rheumatologists expert in the field of RA, who proposed
      and selected by consensus the clinically relevant questions on the role of TNFi
      treatment in DMARDs-naive RA patients. The question was rephrased according to
      the population, intervention, comparison and outcome statement. The available
      scientific evidence on this topic were collected by updating the systematic
      literature reviews used for the EULAR 2013 recommendations up to January 2016.
      The aspects evaluated in the studies concerned clinical efficacy, radiographic
      structural damage and safety. After the systematic literature review the expert
      panel formulated a consensus statement, and a modified Delphi panel evaluated the
      level of agreement between panellists (strength of recommendation). Results: From
      a total of 1080 records we have included 6 studies, 2 randomized clinical trials
      and 4 open-label extension trials. Evidence from publications generated three
      statements for the final consensus document. The systematic literature review and
      the consensus statements developed showed that, for patients with early RA and in
      the presence of a treat-to-target strategy, the immediate use of anti-TNFi
      compared with an early (within 12 weeks) step-up to anti-TNF therapy did not
      confer a significant advantage regarding clinical, functional and radiographic
      outcomes. Conclusion: The most appropriate placement of the TNFi therapy in the
      treatment algorithm of early RA still remains a challenging clinical question
      that needs to be further addressed.

PMID- 30289539
TI  - Switch or swap strategy in rheumatoid arthritis patients failing TNF inhibitors?
      Results of a modified Italian Expert Consensus.
AB  - Objective: To establish evidence-based and experts' opinion filtered statements
      on the optimal treatment choice between cycling (switch) and changing mode of
      action strategies (swap) in RA patients failing TNF inhibitors (TNFis). Methods:
      The relevant question (switch vs swap) was rephrased into a research question
      according to the population, intervention, comparison and outcome (PICO)
      strategy, considering all the available scientific evidence published from the
      2013 EULAR set of recommendations up to mid-January 2016. Final statements
      derived from the retrieved scientific evidence and experts' consensus, with
      eventual rephrasing through a Delphi method during a national consensus of
      Italian rheumatologists. Results: From a total of 365 records, 12 studies were
      finally included. The final statements argued that, until head-to-head comparison
      data are available, switch and swap can be still considered suitable strategies
      in RA patients failing first TNFi, even though some data seem to lend more
      support to a different mode of action-targeted strategy. Conclusion: After
      failure of first TNFi course, switch and swap can be currently considered as
      alternative suitable approaches in RA patients.

PMID- 30289541
TI  - Fluoroscopic Subdural Contrast Flow Pattern in the Lumbar Spine.

PMID- 30289542
TI  - ESTIMATION OF ORGAN DOSES AND EFFECTIVE DOSES BASED ON IN-PHANTOM DOSIMETRY FOR
      INFANT DIAGNOSTIC CARDIAC CATHETERISATIONS WITH NOVEL X-RAY IMAGING TECHNOLOGY.
AB  - The present study evaluated the organ and effective doses in infant diagnostic
      cardiac catheterisation performed using a modern x-ray imaging unit by in-phantom
      dosimetry. In addition, conversion factors from dose-area product (DAP) to
      effective dose were determined. The organ and effective doses in 1-year old
      during diagnostic cardiac catheterisations were measured using
      radiophotoluminescence glass dosemeters implanted into an infant anthropomorphic
      phantom. The mean effective doses, evaluated according to the International
      Commission on Radiologic Protection Publication 103, were 4.0 mSv (range: 1.5-8.7
      mSv). The conversion factors from DAP to effective dose were 2 and 3.5 mSv (Gy
      cm2)-1 for posteroanterior and lateral fluoroscopy, respectively, and 1.8 and 3.3
      mSv (Gy cm2)-1 for posteroanterior and lateral cineangiography, respectively. The
      dose data and conversion factors evaluated in the present study may be useful for
      estimating radiation exposure in infants during diagnostic cardiac
      catheterisation.

PMID- 30289540
TI  - Dose adjustments and discontinuation in TNF inhibitors treated patients: when and
      how. A systematic review of literature.
AB  - Objectives: To review the available evidence concerning the possibility of
      discontinuing and/or tapering the dosage of TNF inhibitors (TNFi) in RA patients
      experiencing clinical remission or low disease activity. Methods: A systematic
      review of the literature concerning the low dosage and discontinuation of TNFi in
      disease-controlled RA patients was performed by evaluation of reports published
      in indexed international journals (Medline via PubMed, EMBASE), in the time frame
      from 8 April 2013 to 15 January 2016. Results: We analysed the literature
      evaluating the efficacy and the safety of two different strategies using TNFi,
      decreasing dosage or discontinuation, in patients experiencing clinical remission
      or low disease activity. After the analysis of online databases, 25 references
      were considered potentially relevant and 16 references were selected. The
      majority of data concerned etanercept and adalimumab. Results suggested the
      induction of stable clinical remission or low disease activity by using TNFi
      followed by a dosage tapering and/or discontinuation of such drugs may be
      associated with the maintenance of a good clinical response in a subset of
      patients affected by early disease. Conclusion: RA patients treated early with
      TNFi and achieving their therapeutic clinical targets seem to maintain their
      clinical response after tapering or discontinuing TNFi. These data may allow
      physicians a more dynamic and tailored management of RA patients.

PMID- 30289544
TI  - Dietary amino acids under hypoxic conditions exacerbates muscle myopathies
      including wooden breast and white stripping.
AB  - The occurrence of wooden breast (WB) and white striping (WS) of broiler breast
      myopathies may be associated with least-cost feed formulations and the inclusion
      of greater amounts of synthetic amino acids. Two experiments were conducted to
      evaluate the effects of supplemental glutamine (Gln-/+, 0 and 1%) and arginine
      (Arg-/+, 0 and 0.25%) in a 2 * 2 factorial arrangement. Experiment 1 consisted of
      8 replicates using 32 pens and focused on live performance to 44 d of age,
      carcass yield, and meat quality evaluations at 45 d of age. Live performance
      parameters including feed intake, BW gain, mortality, and feed conversion were
      evaluated. Post-harvest carcass yield, breast muscle quality (including WB and
      WS), proximate analysis, and mineral analysis of breast muscle and tibia bone
      were also evaluated. Experiment 2 comprised 4 replicates using 8 pens with weekly
      measurements of blood physiology and muscle myopathy development from 21 to 45 d
      of age. Broilers fed supplemental Gln and Arg (Gln+/Arg+) produced broilers with
      greater BW and improved FCR. The WB and WS severity increased with Gln+ diets,
      while only WB increased using Arg+ diets. Weekly observations revealed the
      greatest increase in WB myopathies occurred between 28 to 35 d, while WS
      significantly increased one week later (35 to 42 d). When comparing broilers of
      similar BW at 45 d, Gln+ diets resulted in greater WS scores and percentage
      breast muscle fat. Further analysis of WB and WS scores (independent of treatment
      affect) revealed that increased myopathy scores were associated with increased
      blood CO2, H2CO3, and reduced O2 with increased meat pH, moisture content, and Ca
      concentration. These results indicated that increased muscle Ca is associated
      with increased WB, while increased dietary glutamine and lack of oxygen may have
      resulted in a reverse flux of the citric acid cycle and reduced electron
      transport chain activity resulting in increased WS.

PMID- 30289543
TI  - Adrenoleukodystrophy: Guidance for Adrenal Surveillance in Males Identified by
      Newborn Screen.
AB  - Context: Adrenoleukodystrophy (ALD) is a peroxisomal disorder associated with
      neurologic decompensation and adrenal insufficiency. Newborn screening for ALD
      has recently been implemented in five states with plans to expand to all 50
      states in the United States. Adrenal insufficiency ultimately develops in most
      males with ALD, but the earliest age of onset is not well established. Objective:
      These clinical recommendations are intended to address screening for adrenal
      insufficiency in boys identified to have ALD by newborn screen. Participants:
      Seven members of the Pediatric Endocrine Society Drug and Therapeutics/Rare
      Diseases Committee, with clinical experience treating children with ALD and
      adrenal insufficiency, and a pediatric endocrinologist and laboratory director
      were selected to be on the working committee. Consensus Process: The authors
      comprised the working group and performed systematic reviews of the published
      literature regarding adrenal insufficiency and ALD. The recommendations were
      reviewed and approved by the larger Pediatric Endocrine Society Drug and
      Therapeutics/Rare Diseases Committee and then by the Pediatric Endocrine Society
      Board of Directors. Conclusions: There is limited literature evidence regarding
      monitoring of evolving adrenal insufficiency in male infants and children with
      ALD. The recommendations suggest initiating assessment of adrenal function at
      diagnosis with ALD and regular monitoring to identify boys with adrenal
      insufficiency in a timely manner and prevent life-threatening adrenal crisis.
      These recommendations are intended to serve as an initial guide, with the
      understanding that additional experience will inform future guidelines.

PMID- 30289545
TI  - AN ASSESSMENT OF RADIATION EXPOSURE DOSES IN PATIENTS UNDERGOING PRIMARY
      PERCUTANEOUS CORONARY INTERVENTION BASED ON ANGIOGRAPHIC RECORDS.
AB  - The stochastic and non-stochastic (deterministic) effects of radiation dose in
      patients undergoing primary percutaneous coronary intervention (PPCI) have been
      investigated using data recorded by an angiographic monitoring system. A total of
      132 patients with acute myocardial infarction referred to the angiography
      department of Vali-Asr hospital, Fasa, Iran, during the second half of 2016 were
      recruited. Quantities like dose-area product (DAP), total air kerma (Ka,r) and
      fluoroscopy time (FT) were calculated and converted into effective dose (ED) and
      peak skin dose (PSD). The values for Ka,r, DAP and FT equaled 80 399.20 +/- 63
      312 mGy cm2, 1392.80 +/- 1155.373 mGy and 524.11 +/- 423.057 s, respectively,
      which were within the ranges reported in previous studies. After considering
      standard dose thresholds for Ka,r and PSD, it was revealed that only a small
      portion of patients had reached these thresholds and exceeded them (<3%).
      Moreover, ED < 20 mSv for the majority of patients was fairly consistent with
      results from a recent research in eight Belgian hospitals. It was shown that
      angiographic records are reliable for assessing radiation dose in patients.

PMID- 30289547
TI  - Mitochondrial Heat Shock Protein 60s Interact with What's This Factor 9 to
      Regulate RNA Splicing of ccmFC and rpl2.
AB  - Mitochondrial intron splicing is a plant-specific feature that was acquired
      during the coevolution of eukaryotic host cells and mitochondria. The elimination
      of these introns is facilitated by mitochondrial-targeted proteins encoded by its
      host, nucleus. What's this factor 9 (WTF9), a nucleus-encoded plant organelle RNA
      recognition (PORR) protein, is involved in the splicing of the mitochondrial
      group II introns rpl2 and ccmFC. Disruption of WTF9 causes developmental defects
      associated with the loss of cytochromes c and c1 in Arabidopsis. In the present
      study, using a co-immunoprecipitation assay, we found that HSP60s interacted with
      WTF9, which was further confirmed by a pull-down assay. HSP60s are molecular
      chaperones that assist with protein folding in both eukaryotic and prokaryotic
      cells. However, accumulating evidence suggests that HSP60s also participate in
      other biological functions such as RNA metabolism and RNA protection. In this
      study, we found that consistently with their interaction with WTF9, HSP60s
      interacted with 48 nucleotides of the ccmFC intron. In mutant studies, the double
      mutant hsp60-3a1hsp60-3b1 exhibited a small stature phenotype and reduced
      splicing efficiency for rpl2 and ccmFC. These observations were similar to those
      in wtf9 mutants and suggest that HSP60s are involved in the RNA splicing of rpl2
      and ccmFC introns in mitochondria. Our findings suggest that HSP60s participate
      in mitochondrial RNA splicing through their RNA-binding ability.

PMID- 30289546
TI  - Efficiency and precision of microRNA biogenesis modes in plants.
AB  - Many evolutionarily conserved microRNAs (miRNAs) in plants regulate transcription
      factors with key functions in development. Hence, mutations in the core
      components of the miRNA biogenesis machinery cause strong growth defects. An
      essential aspect of miRNA biogenesis is the precise excision of the small RNA
      from its precursor. In plants, miRNA precursors are largely variable in size and
      shape and can be processed by different modes. Here, we optimized an approach to
      detect processing intermediates during miRNA biogenesis. We characterized a miRNA
      whose processing is triggered by a terminal branched loop. Plant miRNA processing
      can be initiated by internal bubbles, small terminal loops or branched loops
      followed by dsRNA segments of 15-17 bp. Interestingly, precision and efficiency
      vary with the processing modes. Despite the various potential structural
      determinants present in a single a miRNA precursor, DCL1 is mostly guided by a
      predominant structural region in each precursor in wild-type plants. However, our
      studies in fiery1, hyl1 and se mutants revealed the existence of cleavage
      signatures consistent with the recognition of alternative processing
      determinants. The results provide a general view of the mechanisms underlying the
      specificity of miRNA biogenesis in plants.

PMID- 30289548
TI  - A bZIP transcription factor, CaLMF, mediated light-regulated camptothecin
      biosynthesis in Camptotheca acuminata.
AB  - Camptothecin (CPT) has powerful biological activities and its analogs,
      irinothecan and topothecan, are effective anti-cancer drugs for clinical therapy.
      Camptothecin was first isolated from Camptotheca acuminata and its low
      accumulation in planta limits drug supply in the market. Previous works have
      confirmed that many environmental factors and plant hormones/elicitors could
      regulate CPT biosynthesis, but only light irradiance has a negative effect on CPT
      production in C. acuminata. Although light irradiance has been identified as a
      negative CPT biosynthesis regulator in C. acuminata for many years, the
      mechanisms of this regulation are still unknown. In order to search possible
      signal components involved in the process of light-regulated CPT biosynthesis,
      coexpression analysis was carried out according to the transcriptome database of
      Camptotheca above-ground green tissues. From coexpression analysis, a light
      responsive bZIP transcription factor, CaLMF (Light-Mediated CPT biosynthesis
      Factor), was identified and further investigations showed that overexpression of
      CaLMF down-regulated the expression of CPT biosynthesis genes and decreased the
      accumulation of CPT in leaves, while light-regulated expression of CPT
      biosynthesis genes and CPT production were abolished in CaLMF silencing leaves
      under shading treatment. Our results show that CaLMF is a significant light
      signaling component, which mediates light-regulated CPT biosynthesis in C.
      acuminata.

PMID- 30289549
TI  - CellMarker: a manually curated resource of cell markers in human and mouse.
AB  - One of the most fundamental questions in biology is what types of cells form
      different tissues and organs in a functionally coordinated fashion. Larger-scale
      single-cell sequencing and biology experiment studies are now rapidly opening up
      new ways to track this question by revealing substantial cell markers for
      distinguishing different cell types in tissues. Here, we developed the CellMarker
      database (http://biocc.hrbmu.edu.cn/CellMarker/ or http://bio
      bigdata.hrbmu.edu.cn/CellMarker/), aiming to provide a comprehensive and accurate
      resource of cell markers for various cell types in tissues of human and mouse. By
      manually curating over 100 000 published papers, 4124 entries including the cell
      marker information, tissue type, cell type, cancer information and source, were
      recorded. At last, 13 605 cell markers of 467 cell types in 158 human tissues/sub
      tissues and 9148 cell makers of 389 cell types in 81 mouse tissues/sub-tissues
      were collected and deposited in CellMarker. CellMarker provides a user-friendly
      interface for browsing, searching and downloading markers of diverse cell types
      of different tissues. Furthermore, a summarized marker prevalence in each cell
      type is graphically and intuitively presented through a vivid statistical graph.
      We believe that CellMarker is a comprehensive and valuable resource for cell
      researches in precisely identifying and characterizing cells, especially at the
      single-cell level.

PMID- 30289550
TI  - Quantitative Systems Toxicology Analysis of In Vitro Mechanistic Assays Reveals
      Importance of Bile Acid Accumulation and Mitochondrial Dysfunction in TAK-875
      induced Liver Injury.
AB  - TAK-875 (fasiglifam), a GPR40 agonist in development for the treatment of type 2
      diabetes (T2D), was voluntarily terminated in Phase III trials due to adverse
      liver effects. The potential mechanisms of TAK-875 toxicity were explored by
      combining in vitro experiments with quantitative systems toxicology (QST) using
      DILIsym(r), a mathematical representation of drug-induced liver injury. In vitro
      assays revealed that bile acid transporters were inhibited by both TAK-875 and
      its metabolite, TAK-875-Glu. Experimental data indicated that human bile salt
      export pump (BSEP) inhibition by TAK-875 was mixed while sodium taurocholate co
      transporting polypeptide (NTCP) inhibition by TAK-875 was competitive.
      Furthermore, experimental data demonstrated that both TAK-875 and TAK-875-Glu
      inhibit mitochondrial electron transport chain (ETC) enzymes. These mechanistic
      data were combined with a physiologically-based pharmacokinetic (PBPK) model
      constructed within DILIsym to estimate liver exposure of TAK-875 and TAK-875-Glu.
      In a simulated population (SimPopsTM) constructed to reflect T2D patients, 16/245
      (6.5%) simulated individuals developed alanine aminotransferase (ALT) elevations,
      an incidence similar to that observed with 200 mg daily dosing in clinical
      trials. Determining the mode of bile acid transporter inhibition (Ki) was
      critical to accurate predictions. In addition, simulations conducted on a
      sensitive subset of individuals (SimCohortsTM) revealed that when either BSEP or
      ETC inhibition was inactive, ALT elevations were not predicted to occur,
      suggesting that the two mechanisms operate synergistically to produce the
      observed clinical response. These results demonstrate how utilizing QST methods
      to interpret in vitro experimental results can lead to an improved understanding
      of the clinically relevant mechanisms underlying drug-induced toxicity.

PMID- 30289551
TI  - Kids Nowadays Hear Better Than We Did: Declining Prevalence of Hearing Loss in US
      Youth, 1966-2010.
AB  - OBJECTIVES/HYPOTHESIS: To investigate factors associated with hearing impairment
      (HI) in adolescent youths during the period 1966-2010. STUDY DESIGN: Cross
      sectional analyses of US sociodemographic, health, and audiometric data spanning
      5 decades. METHODS: Subjects were youths aged 12 to 17 years who participated in
      the National Health Examination Survey (NHES Cycle 3, 1966-1970; n = 6,768) and
      youths aged 12 to 19 years in the Third National Health and Nutrition Examination
      Survey (NHANES III, 1988-1994; n = 3,057) and NHANES (2005-2010; n = 4,374). HI
      prevalence was defined by pure-tone average (PTA) >= 20 dB HL for speech
      frequencies (0.5, 1, 2, and 4 kHz) and high frequencies (3, 4, and 6 kHz).
      Multivariable logistic models were used to estimate the odds ratio (OR) and 95%
      confidence interval (CI). RESULTS: Overall speech-frequency HI prevalence was
      10.6% (95% CI: 9.7%-11.6%) in NHES, 3.9% (95% CI: 2.8%-5.5%) in NHANES III, and
      4.5% (95% CI: 3.7%-5.4%) in NHANES 2005 to 2010. The corresponding high-frequency
      HI prevalences were 32.8% (95% CI: 30.8%-34.9%), 7.3% (95% CI: 5.9%-9.0%), and
      7.9% (95% CI: 6.8%-9.2%). After adjusting for sociodemographic factors, overall
      high-frequency HI was increased twofold for males and cigarette smoking. Other
      significant risk factors in NHANES 2005 to 2010 included very low birth weight,
      history of ear infections/otitis media, ear tubes, fair/poor general health, and
      firearms use. CONCLUSIONS: HI declined considerably between 1966 to 1970 and 1988
      to 1994, with no additional decline between 1988 to 1994 and 2005 to 2010. Otitis
      media history was a significant HI risk factor each period, whereas very low
      birth weight emerged as an important risk factor after survival chances improved.
      Reductions in smoking, job-related noise, and firearms use may partially explain
      the reduction in high-frequency HI. Loud music exposure may have increased, but
      does not account for HI differences. LEVEL OF EVIDENCE: NA.

PMID- 30289552
TI  - The effectiveness of peer support on self-efficacy and quality of life in adults
      with type 2 diabetes: A systematic review and meta-analysis.
AB  - BACKGROUND: Peer support has been suggested as a promising approach for diabetes
      management. No conclusive evidence exists on the effects of peer support on self
      efficacy and quality of life in adults with type 2 diabetes. OBJECTIVE: To assess
      the effectiveness of peer support on self-efficacy and the quality of life in
      adults with type 2 diabetes. DESIGN: A systematic review and meta-analysis of
      randomized controlled studies. DATA SOURCES: We searched PubMed, Embase, Cochrane
      Central Register of Controlled Trials and Allied Health Literature database guide
      for relevant literatures from inception to 30 September 2017. REVIEW METHODS: The
      review was conducted according to the guidelines of Cochrane Collaboration. The
      outcomes were self-efficacy and quality of life. The standardized mean difference
      and 95% confidence intervals were calculated for pooled results. RESULTS: A total
      of 15 studies met the inclusion criteria. The pooled results revealed that peer
      support did not significantly improve self-efficacy and quality of life in adults
      with type 2 diabetes, but significantly improved self-efficacy and quality of
      life in studies with intervention duration <=6 months. There was no evidence of
      publication bias. CONCLUSION: Peer support intervention did not lead to better
      effects on the improvement in self-efficacy and quality of life among adults with
      type 2 diabetes. However, peer support with intervention duration not more than 6
      months had positive effects on self-efficacy and quality of life. More high
      quality studies with large sample size are needed to support or counter the
      results.

PMID- 30289553
TI  - Ethylene signaling regulates natural variation in the abundance of antifungal
      acetylated diferuloylsucroses and Fusarium graminearum resistance in maize
      seedling roots.
AB  - The production and regulation of defensive specialized metabolites play a central
      role in pathogen resistance in maize (Zea mays) and other plants. Therefore,
      identification of genes involved in plant specialized metabolism can contribute
      to improved disease resistance. We used comparative metabolomics to identify
      previously unknown antifungal metabolites in maize seedling roots, and
      investigated the genetic and physiological mechanisms underlying their natural
      variation using quantitative trait locus mapping and comparative transcriptomics
      approaches. Two maize metabolites, smilaside A (3,6-diferuloyl-3',6'
      diacetylsucrose) and smiglaside C (3,6-diferuloyl-2',3',6'-triacetylsucrose),
      were identified that could contribute to maize resistance against Fusarium
      graminearum and other fungal pathogens. Elevated expression of an ethylene
      signaling gene, ETHYLENE INSENSITIVE 2 (ZmEIN2), co-segregated with a decreased
      smilaside A : smiglaside C ratio. Pharmacological and genetic manipulation of
      ethylene availability and sensitivity in vivo indicated that, whereas ethylene
      was required for the production of both metabolites, the smilaside A : smiglaside
      C ratio was negatively regulated by ethylene sensitivity. This ratio, rather than
      the absolute abundance of these two metabolites, was important for maize seedling
      root defense against F. graminearum. Ethylene signaling regulates the relative
      abundance of the two F. graminearum-resistance-related metabolites and affects
      resistance against F. graminearum in maize seedling roots.

PMID- 30289554
TI  - In Vitro Hydrodynamic Evaluation of a Scaffold for Heart Valve Tissue
      Engineering.
AB  - Although prosthetic heart valves have saved many lives, the search for a living
      substitute continues with the aid of tissue engineering. Much progress has been
      made so far, but the translation of this technology to clinical reality remains a
      challenge, especially due to the structural complexity of heart valves and the
      harsh environment they are in. In a joint effort, researchers from Federal
      University of ABC and Institute Dante Pazzanese of Cardiology have conceived a
      new bioresorbable scaffold for heart valve tissue engineering (HVTE), whose
      hydrodynamic performance was first assessed and described in this work. The
      scaffold was studied at the mitral position of a left heart simulator from Escola
      Politecnica of the University of Sao Paulo, under 60 bpm and with no cell
      seeding. In this condition, two-dimensional particle image velocimetry was
      performed to investigate the flow during diastolic and systolic phases. The
      results indicate that the scaffold can withstand the required intraventricular
      pressures for a simulated normal physiologic condition in a bioreactor.
      Furthermore, the averaged (N = 150) velocity vector maps showed a smooth and well
      distributed flow during diastole and qualitatively demonstrated no-significant
      regurgitation at systole.

PMID- 30289555
TI  - Imaging microstructure of the barley rhizosphere: particle packing and root hair
      influences.
AB  - Soil adjacent to roots has distinct structural and physical properties from bulk
      soil, affecting water and solute acquisition by plants. Detailed knowledge on how
      root activity and traits such as root hairs affect the three-dimensional pore
      structure at a fine scale is scarce and often contradictory. Roots of hairless
      barley (Hordeum vulgare L. cv Optic) mutant (NRH) and its wildtype (WT) parent
      were grown in tubes of sieved (<250 MUm) sandy loam soil under two different
      water regimes. The tubes were scanned by synchrotron-based X-ray computed
      tomography to visualise pore structure at the soil-root interface. Pore volume
      fraction and pore size distribution were analysed vs distance within 1 mm of the
      root surface. Less dense packing of particles at the root surface was
      hypothesised to cause the observed increased pore volume fraction immediately
      next to the epidermis. The pore size distribution was narrower due to a decreased
      fraction of larger pores. There were no statistically significant differences in
      pore structure between genotypes or moisture conditions. A model is proposed that
      describes the variation in porosity near roots taking into account soil
      compaction and the surface effect at the root surface.

PMID- 30289556
TI  - Music intervention for pain and anxiety management of the primiparous women
      during labour: A systematic review and meta-analysis.
AB  - AIMS: To determine the effect of music on the management of pain and anxiety in
      primiparous women during labour. BACKGROUND: Music is cost-effective intervention
      in clinical practice to reduce pain, stress, and anxiety. However, a systematic
      review with meta-analysis for investigating its effects during labour is still
      lacking. DESIGN: A systematic review with meta-analysis. DATA SOURCES: MEDLINE,
      EMBASE, and CINAHL databases. REVIEW METHODS: Randomized controlled trials or
      quasi-experimental trials concerning the effects of music among primiparous women
      who were expected to give normal spontaneous delivery were searched and screened
      up to 31 July 2017. The recruited trials for this review were compliant with the
      standards of the Cochrane Handbook for Systematic Reviews of Interventions.
      RESULTS: A total of 392 primiparous pregnant women (197 in the music intervention
      group and 195 in the routine care group) from five studies were included in this
      review. Music as an intervention seemed to lower the pain scores for primiparous
      women during labour, but the effect was not statistically significant. However,
      there was a significant benefit of music intervention compared with routine care
      for primiparous women during labour. In the sensitivity analysis, music
      intervention showed significant effect on the improvement of pain and anxiety for
      primiparous women during labour. CONCLUSION: Music intervention may be an
      effective intervention for the management of pain and anxiety for primiparous
      women during labour.

PMID- 30289557
TI  - Bibliometric analysis of six nursing journals from the Web of Science, 2012-2017.
AB  - AIM: The purpose of this study was to perform a bibliometric analysis of the six
      most important nursing journals according to the impact factor of the Science
      Citation Index through Web of Science(r) . The following journals were included:
      International Journal of Nursing Studies, Nurse Education Today, Journal of
      Nursing Scholarship, Nursing Outlook, Worldviews on Evidence-Based Nursing and
      the Journal of Advanced Nursing. BACKGROUND: In the nursing field, bibliometric
      analysis and maps have been used to analyse the production of some journals but
      not for the comparison of different journals. DESIGN/METHOD: Using descriptive
      bibliometrics, we studied scientific production of different journals and
      bibliometric maps were used to visualize the content of published articles.
      RESULTS: The six journals included showed that 3,937 articles were written by
      1,1371 authors from 2,980 institutions and 84 countries from 2012 - 2017. Journal
      of Advanced Nursing had a greater number of publications and citations. The most
      prolific authors showed a tendency to publish first in Journal of Advanced
      Nursing and then in International Journal of Nursing Studies and Nurse Education
      Today. The frequency of citation was higher in International Journal of Nursing
      Studies followed by Journal of Advanced Nursing. The most collaborative authors
      and those with the most co-citations published more than half of their
      publications in Journal of Advanced Nursing. The topics most commonly researched
      by these authors were job satisfaction, collaborative practices, and nurse
      leaders. CONCLUSION: This bibliometric analysis contributes to the understanding
      of the current state of nursing research and its evolution.

PMID- 30289558
TI  - Eyes on the future - evidence for trade-offs between growth, storage and defense
      in Norway spruce.
AB  - Carbon (C) allocation plays a central role in tree responses to environmental
      changes. Yet, fundamental questions remain about how trees allocate C to
      different sinks, for example, growth vs storage and defense. In order to
      elucidate allocation priorities, we manipulated the whole-tree C balance by
      modifying atmospheric CO2 concentrations [CO2 ] to create two distinct gradients
      of declining C availability, and compared how C was allocated among fluxes
      (respiration and volatile monoterpenes) and biomass C pools (total biomass,
      nonstructural carbohydrates (NSC) and secondary metabolites (SM)) in well-watered
      Norway spruce (Picea abies) saplings. Continuous isotope labelling was used to
      trace the fate of newly-assimilated C. Reducing [CO2 ] to 120 ppm caused an
      aboveground C compensation point (i.e. net C balance was zero) and resulted in
      decreases in growth and respiration. By contrast, soluble sugars and SM remained
      relatively constant in aboveground young organs and were partially maintained
      with a constant allocation of newly-assimilated C, even at expense of root death
      from C exhaustion. We conclude that spruce trees have a conservative allocation
      strategy under source limitation: growth and respiration can be downregulated to
      maintain 'operational' concentrations of NSC while investing newly-assimilated C
      into future survival by producing SM.

PMID- 30289559
TI  - Enhancing validity through cognitive interviewing. A methodological example using
      the Epilepsy Monitoring Unit Comfort Questionnaire.
AB  - AIMS: To identify problematic items, assess completeness and user-friendliness,
      and undertake modifications to enhance face validity of the newly developed
      Epilepsy Monitoring Unit Comfort Questionnaire. DESIGN: Qualitative-descriptive
      cross-sectional study. METHODS: Five iterative rounds of cognitive interviewing
      were conducted with members of the target population between July - November
      2017. Think-aloud technique, verbal probing, and observation were used, to assess
      how respondents understood and answered questions. Data analysis was based on the
      framework method; an eight-column framework matrix was created for this purpose.
      RESULTS: In 25 interviews, problems regarding completeness of the item pool,
      comprehension of items, retrieval of information, judgment while finding answers
      and reporting the appropriate responses could be detected. According to the
      results, 27 items remained unchanged, 11 items were reworded, and six items were
      added. Instructions section of the questionnaire was reworked, too. CONCLUSION:
      Although time-consuming, cognitive interviewing turned out to be a valuable
      approach for revealing problems in an instrument, which would, otherwise, remain
      undetected and threaten validity.

PMID- 30289560
TI  - OsTPS8 controls yield-related traits and confers salt stress tolerance in rice by
      enhancing suberin deposition.
AB  - Class I TREHALOSE-PHOSPHATE-SYNTHASE (TPS) genes affect salinity tolerance and
      plant development. However, the function of class IITPS genes and their
      underlying mechanisms of action are unknown. We report the identification and
      functional analysis of a rice class IITPS gene (OsTPS8). The ostps8 mutant was
      characterised by GC-MS analysis, an abscisic acid (ABA) sensitivity test and by
      generating transgenic lines. To identify the underlying mechanism, gene
      expression analyses, genetic complementation and examination of suberin
      deposition in the roots were conducted. The ostps8 mutant showed salt
      sensitivity, ABA sensitivity and altered agronomic traits compared to the wild
      type (WT), which could be rescued upon complementation. The dsRNAi line
      phenocopied the mutant, while the overexpression lines exhibited enhanced salt
      tolerance. The ostps8 mutant showed significantly reduced soluble sugars,
      Casparian bands and suberin deposition in the roots compared to the WT and
      overexpression lines. The mutant also showed downregulation of SAPKs (rice
      SnRK2s) and ABA-responsive genes. Furthermore, ostps8pUBI::SAPK9 rescued the salt
      sensitive phenotype of ostps8. Our results suggest that OsTPS8 may regulate
      suberin deposition in rice through ABA signalling. Additionally, SAPK9-mediated
      regulation of altered ABA-responsive genes helps to confer salinity tolerance.
      Overexpression of OsTPS8 was adequate to confer enhanced salinity tolerance
      without any yield penalty, suggesting its usefulness in rice genetic improvement.

PMID- 30289561
TI  - Quantitative measure of fitness in tri-trophic interactions and its influence on
      diet breadth of insect herbivores.
AB  - Herbivore-plant interactions should be studied using a tri-trophic approach, but
      we lack a quantitative measure of the combined effect of top-down and bottom-up
      forces on herbivore fitness. We propose the combination of the bi-trophic fitness
      slopes as a tri-trophic fitness measure. We use the relationship between fitness
      associated with top-down and bottom-up forces and the frequency of host plant use
      to calculate the top-down and bottom-up fitness slopes, which we then combine to
      obtain three possible directions of tri-trophic slopes. A positive tri-trophic
      slope indicates that herbivores have overall greater tri-trophic fitness on the
      more frequently used hosts. A null tri-trophic fitness slope indicates that
      herbivores have similar fitness on all host plants. A negative tri-trophic slope
      indicates that herbivores have generally lower fitness on the more frequently
      used hosts. We tested the explanation power of our method using data from the
      literature that tested herbivore host shifts and experimentally using a
      generalist herbivore with variable diet breadth across populations. We found that
      in host shifts, herbivores have higher tri-trophic fitness on the novel host,
      while in generalist populations, herbivores use most frequently the best host
      available. We present applications in other research areas and consider the
      limitations of our approach. Our approach is a first step towards a comprehensive
      model of multiple selective forces acting on the evolution of interactions.

PMID- 30289562
TI  - Maternal functional hemodynamics in uncomplicated twin pregnancies: A
      longitudinal study using impedance cardiography.
AB  - INTRODUCTION: Longitudinal studies of maternal hemodynamics in twin pregnancy are
      scarce and preload reserve in twin pregnancies has not been studied. Thus, we
      aimed to investigate serial changes in maternal systemic hemodynamics from the
      first to third trimester, and cardiovascular response to passive leg raising to
      evaluate preload reserve using impedance cardiography in a cohort of
      uncomplicated twin pregnancies. MATERIAL AND METHODS: This was a prospective
      longitudinal study of 50 twin pregnancies. Maternal hemodynamics was assessed at
      baseline and 120 seconds after passive leg raising using impedance cardiography,
      at five time points during gestation. Women were excluded from the analysis if
      there were pregnancy complications or fewer than three of five planned
      assessments were available. RESULTS: Data from 37 uncomplicated twin pregnancies
      were available for analysis. Mean arterial pressure slightly decreased until 17
      weeks' gestation, then increased. Systemic vascular resistance was constant in
      the first half of pregnancy before rising steadily thereafter, whereas the
      cardiac output increased from the first trimester, peaked by the end of the
      second trimester and then decreased in the third trimester. The change in stroke
      volume and cardiac output following passive leg raising during pregnancy ranged
      from -2.2% to 1.6% and from -3.7% to 3.2%, respectively. Although passive leg
      raising caused no significant changes in systemic vascular resistance, cardiac
      output or heart rate, mean arterial pressure decreased in the first and second
      trimesters. CONCLUSIONS: In uncomplicated twin pregnancies, maternal
      cardiovascular adaptation is evident from the first trimester. Twin pregnancies
      show a reduced preload reserve in the second half of gestation.

PMID- 30289563
TI  - Determinants of non-adherence to antiretroviral therapy among Option B+ cases in
      Ndop and Fundong health districts, Northwest Region, Cameroon.

PMID- 30289564
TI  - Regulatory IFN-gamma-producing killer dendritic cells are enhanced in B6.MLR
      Faslpr /J lupus-prone mice.
AB  - A novel cell population denominated IFN-gamma-producing killer dendritic cells
      (IKDCs) have been recently described. These cells are lymphocytes lacking B- or T
      receptors, but they can be identified by the presence of B220+ CD38+ CD49b+ and
      low CD11c, among other cell surface markers. The main characteristics of IKDCs
      are the production of IFN-gamma and the ability to spontaneously kill tumor
      cells. We found that this population increases in B6.MLR-Faslpr /J mice.
      Interestingly, IKDCs increase with age and are more abundant in mice older than 6
      months onward. To analyze whether these cells have any role in the induction of
      the lupus-like phenotype in the B6.MLR-Faslpr /J mice, IKDCs were purified and
      transferred into 6-month-old B6.MRL-Faslpr /J mice, then the presence of anti
      nuclear antibodies (ANAS) and anti-dsDNA antibodies were analyzed 2 and 4 months
      after the transfer. The results showed a reduction in the levels of these
      autoantibodies and increased survival of these mice, indicating that these cells
      may have a regulatory function. In vitro assays demonstrated that IKDCs reduced
      the proliferation of both autoreactive B and T cells, suggesting that these may
      be the mechanisms used by these cells to ameliorate the lupus-like phenotype in
      the B6.MRL-Faslpr /J mice.

PMID- 30289565
TI  - Interventionist versus expectant care for severe pre-eclampsia between 24 and 34
      weeks' gestation.
AB  - BACKGROUND: Severe pre-eclampsia can cause significant mortality and morbidity
      for both mother and child, particularly when it occurs remote from term, between
      24 and 34 weeks' gestation. The only known cure for this disease is delivery.
      Some obstetricians advocate early delivery to ensure that the development of
      serious maternal complications, such as eclampsia (fits) and kidney failure are
      prevented. Others prefer a more expectant approach, delaying delivery in an
      attempt to reduce the mortality and morbidity for the child that is associated
      with being born too early. OBJECTIVES: To evaluate the comparative benefits and
      risks of a policy of early delivery by induction of labour or by caesarean
      section, after sufficient time has elapsed to administer corticosteroids, and
      allow them to take effect; with a policy of delaying delivery (expectant care)
      for women with severe pre-eclampsia between 24 and 34 weeks' gestation. SEARCH
      METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials
      Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry
      Platform (ICTRP) on 27 November 2017, and reference lists of retrieved studies.
      SELECTION CRITERIA: Randomised trials comparing the two intervention strategies
      for women with early onset, severe pre-eclampsia. Trials reported in an abstract
      were eligible for inclusion, as were cluster-trial designs. We excluded quasi
      randomised trials. DATA COLLECTION AND ANALYSIS: Three review authors
      independently assessed trials for inclusion and risk of bias, extracted data, and
      checked them for accuracy. We assessed the quality of the evidence for specified
      outcomes using the GRADE approach. MAIN RESULTS: We included six trials, with a
      total of 748 women in this review. All trials included women in whom there was no
      overriding indication for immediate delivery in the fetal or maternal interest.
      Half of the trials were at low risk of bias for methods of randomisation and
      allocation concealment; and four trials were at low risk for selective reporting.
      For most other domains, risk of bias was unclear. There were insufficient data
      for reliable conclusions about the comparative effects on most outcomes for the
      mother. Two studies reported on maternal deaths; neither study reported any
      deaths (two studies; 320 women; low-quality evidence). It was uncertain whether
      interventionist care reduced eclampsia (risk ratio (RR) 0.98, 95% confidence
      interval (CI) 0.06 to 15.58; two studies; 359 women) or pulmonary oedema (RR
      0.45, 95% CI 0.07 to 3.00; two studies; 415 women), because the quality of the
      evidence for these outcomes was very low. Evidence from two studies suggested
      little or no clear difference between the interventionist and expectant care
      groups for HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome
      (RR 1.09, 95% CI 0.62 to 1.91; two studies; 359 women; low-quality evidence). No
      study reported on stroke. With the addition of data from two studies for this
      update, there was now evidence to suggest that interventionist care probably made
      little or no difference to the incidence of caesarean section (average RR 1.01,
      95% CI 0.91 to 1.12; six studies; 745 women; Heterogeneity: Tau2 = 0.01; I2 =
      63%).For the baby, there was insufficient evidence to draw reliable conclusions
      about the effects on perinatal deaths (RR 1.11, 95% CI 0.62 to 1.99; three
      studies; 343 women; low-quality evidence). Babies whose mothers had been
      allocated to the interventionist group had more intraventricular haemorrhage (RR
      1.94, 95% CI 1.15 to 3.29; two studies; 537 women; moderate-quality evidence),
      more respiratory distress caused by hyaline membrane disease (RR 2.30, 95% CI
      1.39 to 3.81; two studies; 133 women), required more ventilation (RR 1.50, 95% CI
      1.11 to 2.02; two studies; 300 women), and were more likely to have a lower
      gestation at birth (mean difference (MD) -9.91 days, 95% CI -16.37 to -3.45 days;
      four studies; 425 women; Heterogeneity: Tau2 = 31.74; I2 = 76%). However, babies
      whose mothers had been allocated to the interventionist group were no more likely
      to be admitted to neonatal intensive care (average RR 1.19, 95% CI 0.89 to 1.60;
      three studies; 400 infants; Heterogeneity: Tau2 = 0.05; I2 = 84%). Babies born to
      mothers in the interventionist groups were more likely to have a longer stay in
      the neonatal intensive care unit (MD 7.38 days, 95% CI -0.45 to 15.20 days; three
      studies; 400 women; Heterogeneity: Tau2 = 40.93, I2 = 85%) and were less likely
      to be small-for-gestational age (RR 0.38, 95% CI 0.24 to 0.61; three studies; 400
      women). There were no clear differences between the two strategies for any other
      outcomes. AUTHORS' CONCLUSIONS: This review suggested that an expectant approach
      to the management of women with severe early onset pre-eclampsia may be
      associated with decreased morbidity for the baby. However, this evidence was
      based on data from only six trials. Further large, high-quality trials are needed
      to confirm or refute these findings, and establish if this approach is safe for
      the mother.

PMID- 30289566
TI  - Drivers of species turnover vary with species commonness for native and alien
      plants with different residence times.
AB  - Communities comprising alien species with different residence times are natural
      experiments allowing the assessment of drivers of community assembly over time.
      Stochastic processes (such as dispersal and fluctuating environments) should be
      the dominant factors structuring communities of exotic species with short
      residence times. In contrast, communities should become more similar, or
      systematically diverge, if they contain exotics with increasing resident times,
      due to the increasing importance of deterministic processes (such as
      environmental filtering). We use zeta diversity (the number of species shared by
      multiple assemblages) to explore the relationship between the turnover of native
      species and two categories of alien species with different residence times
      (archaeophytes [introduced between 4000 BC and 1500 AD] and neophytes [introduced
      after 1500 AD]) in a network of nature reserves in central Europe. By considering
      multiple assemblages simultaneously, zeta diversity allows us to determine the
      contribution of rare and widespread species to turnover. Specifically, we explore
      the relative effects of assembly processes representing isolation by distance,
      environmental filtering, and environmental stochasticity (fluctuating
      environments) on zeta diversity using Multi-Site Generalized Dissimilarity
      Modelling (MS-GDM). Four clusters of results emerged. First, stochastic processes
      for structuring plant assemblages decreased in importance with increasing
      residence time. Environmental stochasticity only affected species composition for
      neophytes, offering possibilities to predict the spread debt of recent invasions.
      Second, native species turnover was well explained by environmental filtering and
      isolation by distance, although these factors did not explain the turnover of
      archaeophytes and neophytes. Third, native and alien species compositions were
      only correlated for rare species, whereas turnover in widespread alien species
      was surprisingly unrelated to the composition of widespread native species. Site
      specific approaches would therefore be more appropriate for the monitoring and
      management of rare alien species, whereas species-specific approaches would suit
      widespread species. Finally, the size difference of nature reserves influences
      not only native species richness, but also their richness-independent turnover. A
      network of reserves must therefore be designed and managed using a variety of
      approaches to enhance native diversity, while controlling alien species with
      different residence times and degrees of commonness.

PMID- 30289567
TI  - Manipulating host resistance structure reveals impact of pathogen dispersal and
      environmental heterogeneity on epidemics.
AB  - Understanding how variation in hosts, parasites, and the environment shapes
      patterns of disease is key to predicting ecological and evolutionary outcomes of
      epidemics. Yet in spatially structured populations, variation in host resistance
      may be spatially confounded with variation in parasite dispersal and
      environmental factors that affect disease processes. To tease apart these disease
      drivers, we paired surveys of natural epidemics with experiments manipulating
      spatial variation in host susceptibility to infection. We mapped epidemics of the
      wind-dispersed powdery mildew pathogen Podosphaera plantaginis in five
      populations of its plant host, Plantago lanceolata. At 15 replicate sites within
      each population, we deployed groups of healthy potted 'sentinel' plants from five
      allopatric host lines. By tracking which sentinels became infected in the field
      and measuring pathogen connectivity and microclimate at those sites, we could
      test how variation in these factors affected disease when spatial variation in
      host resistance and soil conditions was minimized. We found that the prevalence
      and severity of sentinel infection varied over small spatial scales in the field
      populations, largely due to heterogeneity in pathogen prevalence on wild plants
      and unmeasured environmental factors. Microclimate was critical for disease
      spread only at the onset of epidemics, where humidity increased infection risk.
      Sentinels were more likely to become infected than initially healthy wild plants
      at a given field site. However, in a follow-up laboratory inoculation study we
      detected no significant differences between wild and sentinel plant lines in
      their qualitative susceptibility to pathogen isolates from the field populations,
      suggesting that primarily non-genetic differences between sentinel and wild hosts
      drove their differential infection rates in the field. Our study leverages a
      multi-faceted experimental approach to disentangle important biotic and abiotic
      drivers of disease patterns within wild populations.

PMID- 30289568
TI  - Thermal adaptation and plasticity of the plant circadian clock.
AB  - Contents Summary I. Introduction II. Molecular organization of the plant
      circadian clock III. Temperature compensation IV. Temperature regulation of
      circadian behaviors V. Thermal adaptation of the clock: evolutionary
      considerations VI. Light and temperature information for the clock function -
      synergic or individual? VII. Concluding remarks and future prospects
      Acknowledgements References SUMMARY: Plant growth and development is widely
      affected by diverse temperature conditions. Although studies have been focused
      mainly on the effects of stressful temperature extremes in recent decades,
      nonstressful ambient temperatures also influence an array of plant growth and
      morphogenic aspects, a process termed thermomorphogenesis. Notably, accumulating
      evidence indicates that both stressful and nonstressful temperatures modulate the
      functional process of the circadian clock, a molecular timer of biological
      rhythms in higher eukaryotes and photosynthetic prokaryotes. The circadian clock
      can sustain robust and precise timing over a range of physiological temperatures.
      Genes and molecular mechanisms governing the temperature compensation process
      have been explored in different plant species. In addition, a ZEITLUPE/HSP90
      mediated protein quality control mechanism helps plants maintain the thermal
      stability of the clock under heat stress. The thermal adaptation capability and
      plasticity of the clock are of particular interest in view of the growing concern
      about global climate changes. Considering these circumstances in the field, we
      believe that it is timely to provide a provoking discussion on the current
      knowledge of temperature regulation of the clock function. The review also will
      discuss stimulating ideas on this topic along with ecosystem management and
      future agricultural innovation.

PMID- 30289569
TI  - Prevalence and risk indicators of peri-implant diseases in Spain.
AB  - AIM: To evaluate the prevalence of peri-implant diseases in Spain, as well as the
      associated risk indicators. MATERIAL AND METHODS: This is a cross-sectional study
      using a network of sentinel dentists, who randomly selected 10 patients with
      implants (placed, at least, 5 years before), which were clinically and
      radiographically evaluated. Case definitions were established for peri-implant
      mucositis [bleeding on probing (BOP) and no bone level >=2 mm] and peri
      implantitis (BOP plus bone level >=2 mm). Potential predictor variables, at
      univariate and multivariate levels, were explored by means of binary logistic
      regression. RESULTS: A total of 49 sentinel dentists provided complete data from
      474 implants in 275 patients. At implant level, prevalences for peri-implant
      mucositis and peri-implantitis were 27% (95% confidence interval [CI] 22-32) and
      20% (95% CI: 15-24), respectively, with 17% of implants (14-21) with bone level
      >=2 mm without BOP. At patient level, prevalences were 27% (22-32), 24% (19-29)
      and 18% (13-22), respectively. In the multiple regression analysis, statistically
      significant associations for peri-implantitis (p < 0.10) were found for gender,
      peri-implant supportive therapy, implant location, diameter and surface, type of
      prosthesis and access to interproximal hygiene. CONCLUSIONS: In this
      representative subject sample across Spain, the prevalence of peri-implant
      diseases was high (51%).

PMID- 30289570
TI  - Hospital admissions and place of death of residents of care homes receiving
      specialist healthcare services: Protocol for a systematic review.
AB  - AIM: To synthesize the evidence relating to the ability of specialist care home
      support services to prevent the hospital admission of older care home residents,
      including hospital admission at the end-of-life. DESIGN: Systematic review and
      narrative synthesis. METHODS: Ten electronic databases will be searched from 2010
      - 31 December 2018 using predetermined search terms. All studies of specialist
      healthcare services to meet care home residents' physical healthcare needs which
      provide outcome data on hospital admission or place of death compared with usual
      care will be included. Two reviewers will independently assess studies'
      eligibility and methodological quality using the Effective Public Health Practice
      Project Quality Assessment Tool. Data will be extracted by one reviewer and
      checked by a second according to predetermined categories. Data will be
      synthesized in evidence tables and narrative. Funder: National Institute for
      Health Research School for Social Care Research, November 2016. DISCUSSION: Care
      of older people in care home settings is a key aspect of nursing nationally and
      internationally. This review will increase understanding of the extent to which
      different models of specialist healthcare support for care homes are associated
      with key resident outcomes. IMPACT: Standard healthcare support for care home
      residents is often inadequate, resulting in avoidable hospital admissions and
      lack of resident choice as to place of death. Although a range of specialist
      healthcare services are emerging, little is known about their relative
      effectiveness. This paper marshalls evidence of relevance to commissioners
      investing in healthcare provision to care homes to meet NHS targets.

PMID- 30289571
TI  - Integrating spatial and phylogenetic information in the fourth-corner analysis to
      test trait-environment relationships.
AB  - The fourth-corner analysis aims to quantify and test for relationships between
      species traits and site-specific environmental variables, mediated by site
      specific species abundances. Since there is no common unit of observation, the
      significance of the relationships is tested using a double permutation procedure
      (site based and species based). This method implies that all species and sites
      are independent of each other. However, this fundamental hypothesis might be
      flawed because of phylogenetic relatedness between species and spatial
      autocorrelation in the environmental data. Here, using a simulation-based
      experiment, we demonstrate how the presence of spatial and phylogenetic
      autocorrelations can, in some circumstances, lead to inflated type I error rates,
      suggesting that significant associations can be misidentified. As an alternative,
      we propose a new randomization approach designed to avoid this issue, based on
      Moran's spectral randomization. In this approach, standard permutations are
      replaced by constrained randomizations so that the distribution of the statistic
      under the null hypothesis is built with additional constraints to preserve the
      phylogenetic and spatial structures of the observed data. The inclusion of this
      new randomization approach provides total control over type I error rates and
      should be used in real studies where spatial and phylogenetic autocorrelations
      often occur.

PMID- 30289572
TI  - Prediction of therapeutic response before and during i.v. cyclophosphamide pulse
      therapy for interstitial lung disease in systemic sclerosis: A longitudinal
      observational study.
AB  - There have been no established parameters to predict responsiveness to i.v.
      cyclophosphamide (IVCY) pulse therapy in combination with corticosteroids in
      patients with interstitial lung disease (ILD) related to systemic sclerosis
      (SSc). This retrospective study was conducted to determine predictive factors for
      efficacy of IVCY at the time of before and during the treatment. Thirty-two
      Japanese SSc patients, ever treated for ILD with IVCY in combination with
      prednisolone, were analyzed retrospectively. We performed detailed time-course
      analyses of parameters derived from blood samples and pulmonary function tests.
      With the exclusion of eight unclassified patients, 24 patients were classified
      into 14 good responders (GR) or 10 poor responders (PR) on the basis of changes
      in percent predicted diffusing capacity for carbon monoxide (DLco). Pretreatment
      percent predicted DLco was significantly reduced in PR compared with GR. In
      addition, serum parameters such as Krebs von den Lungen-6 (KL-6), surfactant
      protein D (SP-D) and C-reactive protein were significantly higher in PR than in
      GR. Furthermore, our time-course analyses revealed a transient increase in serum
      KL-6 levels with a peak at 3 months after the first infusion of cyclophosphamide,
      which showed no relation to therapeutic efficacy. Moreover, continuously high
      serum KL-6 levels (>2000 U/mL) and rapid decrease in SP-D levels (<200 ng/mL)
      during IVCY were remarkably characteristic of PR and GR, respectively. ILD
      severity/activity before treatment and variability of serum KL-6 and SP-D levels
      during treatment may be useful to predict therapeutic effects of IVCY on SSc-ILD.

PMID- 30289573
TI  - Hepatology Highlights.

PMID- 30289574
TI  - Serum amyloid A levels in the blood of patients with atopic dermatitis and
      cutaneous T-cell lymphoma.
AB  - Serum amyloid A (SAA) is an acute phase protein, which activates immune cells and
      induces cytokines and chemokine. SAA levels in blood have been reported to be
      elevated in case of inflammation, infections, neoplasia and tissue injury. In
      this study, we examined SAA levels in the blood of patients with atopic
      dermatitis (AD) and cutaneous T-cell lymphoma (CTCL). SAA levels in sera of AD
      patients, those of CTCL patients and those of healthy controls were not
      significantly different. When AD or CTCL patients were classified by disease
      severity, there was still no difference in SAA levels. In AD patients, however,
      SAA levels positively correlated with the number of eosinophils in peripheral
      blood and serum soluble interleukin-2 receptor (sIL-2R) levels. There were
      significant correlations between SAA levels in blood and the number of white
      blood cells in peripheral blood and serum sIL-2R levels in CTCL patients. AD
      patients without topical steroid treatment and CTCL patients without narrowband
      ultraviolet B therapy showed increased levels of SAA, which suggested that SAA
      levels may easily fluctuate with treatment. These results imply a possible
      contribution of SAA in development of AD and CTCL.

PMID- 30289575
TI  - Exploration of resistance mechanisms for epidermal growth factor receptor
      tyrosine kinase inhibitors based on plasma analysis by digital polymerase chain
      reaction and next-generation sequencing.
AB  - Liquid biopsy offers a potential alternative to tissue biopsy for detection of
      genetic alterations in cancer, and it has been introduced into clinical practice
      to detect the tyrosine kinase inhibitor (TKI) resistance-conferring T790M
      mutation of epidermal growth factor receptor (EGFR) in patients with non-small
      cell lung cancer (NSCLC). We prospectively collected tumor and plasma samples
      from 25 NSCLC patients who harbored activating mutations of EGFR and experienced
      failure of treatment with afatinib. The samples were analyzed by digital PCR
      (dPCR) and next-generation sequencing (NGS). T790M was detected in plasma with a
      respective sensitivity and specificity of 83.3% and 70.0% by dPCR and 50.0% and
      70.0% by NGS relative to analysis of corresponding tumor samples. Quantitation of
      T790M based on the ratio of the number of T790M alleles to that of activating
      mutation alleles (T/A ratio) improved the specificity of plasma analysis to 100%
      for both dPCR and NGS without a reduction in sensitivity. Although several
      afatinib resistance mechanisms other than T790M-including copy number gain of
      NRAS or MET-were identified in tumor samples, the corresponding genetic
      alterations were not detected in plasma. TP53 mutations were frequently
      identified in plasma and tumor samples, with most such mutations also having been
      detected before afatinib treatment. The presence of de novo TP53 mutations was
      associated with reduced progression-free survival. Quantitation of T790M in
      plasma is thus a clinically relevant approach to determine the T790M status of
      tumors. In addition, genetic alterations coexisting with EGFR mutations can
      affect the efficacy of EGFR-TKI treatment.

PMID- 30289577
TI  - Enantioselective Cobalt(III)-Catalyzed C-H Activation Enabled by Chiral
      Carboxylic Acid Cooperation.
AB  - The enantioselective cobalt(III)-catalyzed C-H alkylation was achieved through
      the design of a novel chiral acid. The cobalt(III)-catalyzed enantioselective C-H
      activation was characterized by high position-, regio- and enantio-control under
      exceedingly mild reaction conditions. Thereby, the robust cooperative cobalt(III)
      catalysis proved tolerant of valuable electrophilic functional groups, including
      hydroxyl, bromo, and iodo substituents. Mechanistic studies revealed a
      considerable additive effect on kinetics and on a negative non-linear-effect.

PMID- 30289578
TI  - Medication history assessment in research: A randomized controlled trial
      comparing tablet-based (eMedHAT) versus structured interview (MedHAT).
AB  - PURPOSE: Accurate capture of medication use is important for high quality
      research. For epidemiologic studies, medication histories are the most common
      measure of exposure when trying to identify associations between medications and
      outcomes. Concomitant medications can alter the efficacy or safety of study drugs
      in clinical trials. However, there are few studies evaluating the accuracy and
      efficiency of methods to collect these histories. The objective of this study is
      to compare the accuracy of medication histories collected by structured interview
      to histories captured using a tablet-based application. METHODS: This was a
      randomized controlled trial. Subjects were instructed to record all prescription
      medications, non-prescription medications, vitamins, and dietary supplements in a
      diary for 30 days. At the end of the diary collection, subjects were randomized
      to providing a medication history during a structured interview by a trained
      research assistant (MedHAT) or using a tablet-based application (eMedHAT). The
      accuracy of these histories was compared using an adjusted analysis. We also
      measured the duration of the history collection and data entry. RESULTS: A total
      of 111 subjects were in the MedHAT group and 109 subjects were in the eMedHAT
      group. Recall of medications for the 30-day period was similar for MedHAT and
      eMedHAT (76.9% versus 75.2%, respectively). The total time required for
      researchers and subjects for history collection and data entry was 16 minutes
      shorter for the tablet-based method. CONCLUSIONS: Tablet-based medication
      histories were as accurate as histories obtained by research assistants and
      required less time for the researcher.

PMID- 30289579
TI  - Ion-Reagent Interactions Contributing to Ionic Liquid Solvent Effects on a
      Condensation Reaction.
AB  - Molecular dynamics simulations of solutions of hexan-1-amine or 4
      methoxybenzaldehyde in acetonitrile, an ionic liquid/acetonitrile mixture (chiIL
      =0.2), and a number of different (neat) ionic liquids were performed, to further
      understand the solvent effects on the condensation reaction of these species.
      This work indicates that, in the presence of an ionic liquid, the amine group of
      hexan-1-amine is exclusively solvated by the components of the ionic liquid, and
      not by acetonitrile, and that the anion interacts with the aldehyde group of 4
      methoxybenzaldehyde. These interactions showed little dependence on the
      proportion of the ionic liquid present. When varying the cation of the ionic
      liquid there were changes in the cation-amine interaction, and 1-butyl-2,3
      dimethylimidazolium bis(trifluoromethanesulfonyl)imide ([Bm2 im][N(CF3 SO2 )2 ])
      was found to order more than expected about the amine. This ordering is likely
      the origin of the large rate constant values determined in [Bm2 im][N(CF3 SO2 )2
      ] for this condensation reaction and explains an anomaly seen previously. When
      changing the anion, changes were seen in the interactions between both the cation
      and anion with hexan-1-amine, and the anion with 4-methoxybenzaldehyde. The
      differing magnitude of these interactions likely causes subtle changes in the
      activation parameters for this condensation reaction, and provides an explanation
      for the anomalous rate constant values previously determined when varying the
      anion.

PMID- 30289580
TI  - In-Plane Epitaxial Growth of Highly c-Oriented NH2 -MIL-125(Ti) Membranes with
      Superior H2 /CO2 Selectivity.
AB  - Preferred-orientation control has significant impact on the separation
      performance of MOF membranes. Under most conditions the preferred orientation of
      MOF membranes is dominated by the Van der Drift mechanism of evolutionary growth
      selection so that the obtained orientation may not be optimized for practical
      application. In this study, highly c-oriented NH2 -MIL-125 membranes were
      prepared on porous alpha-alumina substrates by combining oriented seeding and
      controlled in-plane epitaxial growth. Dynamic air-liquid interface-assisted self
      assembly of c-oriented NH2 -MIL-125(Ti) seed monolayers, the use of layered TiS2
      as the metal precursor, and single-mode microwave heating were crucial in
      ensuring the preferred c-orientation while simultaneously suppressing undesired
      twin growth. Owing to reduced grain boundary defects, the prepared c-oriented
      membranes showed an ideal H2 /CO2 selectivity of 24.8, which was 6.1 times higher
      than that of their randomly oriented counterparts under similar operating
      conditions.

PMID- 30289576
TI  - Transduced caudal-type homeobox (CDX) 2/CDX1 can induce growth inhibition on CDX
      deficient gastric cancer by rapid intestinal differentiation.
AB  - Intestinal metaplasia induced by ectopic expression of caudal-type homeobox
      (CDX)2 and/or CDX1 (CDX) is frequently observed around gastric cancer (GC).
      Abnormal expression of CDX is also observed in GC and suggests that inappropriate
      gastrointestinal differentiation plays essential roles in gastric tumorigenesis,
      but their roles on tumorigenesis remain unelucidated. Publicly available
      databases show that GC patients with higher CDX expression have significantly
      better clinical outcomes. We introduced CDX2 and CDX1 genes separately into GC
      originated MKN7 and TMK1 cells deficient in CDX. Marked suppression of cell
      growth and dramatic morphological change into spindle-shaped flat form were
      observed along with induction of intestinal marker genes. G0-G1 growth arrest was
      accompanied by changed expression of cell cycle-related genes but not with
      apoptosis or senescence. Microarray analyses additionally showed decreased
      expression of gastric marker genes and increased expression of stemness
      associated genes. Hierarchical clustering of 111 GC tissues and 21 non-cancerous
      gastric tissues by selected 18 signature genes based on our transcriptome
      analyses clearly categorized the 132 tissues into non-cancer, "CDX signature"
      positive GC, and "CDX signature"-negative GC. Gene set enrichment analysis
      indicated that "CDX signature"-positive GC has lower malignant features.
      Immunohistochemistry of 89 GC specimens showed that 50.6% were CDX2-deficient,
      66.3% were CDX1-deficient, and 44.9% were concomitant CDX2/CDX1-deficient,
      suggesting that potentially targetable GC cases by induced intestinal
      differentiation are quite common. In conclusion, exogenous expression of
      CDX2/CDX1 can lead to efficient growth inhibition of CDX-deficient GC cells. It
      is based on rapidly induced intestinal differentiation, which may be a future
      therapeutic strategy.

PMID- 30289581
TI  - Fluoride-Free Synthesis of Two-Dimensional Titanium Carbide (MXene) Using A
      Binary Aqueous System.
AB  - Two-dimensional (2D) titanium carbide (Ti3 C2 ) is emerging as an important
      member of the MXene family. However, fluoride-based synthetic procedures remain
      an impediment to the practical applications of this promising class of materials.
      Here we demonstrate an efficient fluoride-free etching method based on the anodic
      corrosion of titanium aluminium carbide (Ti3 AlC2 ) in a binary aqueous
      electrolyte. The dissolution of aluminium followed by in situ intercalation of
      ammonium hydroxide results in the extraction of carbide flakes (Ti3 C2 Tx , T=O,
      OH) with sizes up to 18.6 MUm and high yield (over 90 %) of mono- and bilayers.
      All-solid-state supercapacitor based on exfoliated sheets exhibits high areal and
      volumetric capacitances of 220 mF cm-2 and 439 F cm-3 , respectively, at a scan
      rate of 10 mV s-1 , superior to those of LiF/HCl-etched MXenes. Our strategy
      paves a safe way to the scalable synthesis and application of MXene materials.

PMID- 30289583
TI  - "To know or not to know...?" Push and pull in ever smokers lung screening uptake
      decision-making intentions.
AB  - BACKGROUND: In the United States, lung cancer screening aims to detect cancer
      early in nonsymptomatic current and former smokers. A lung screening pilot
      service in an area of high lung cancer incidence in the United Kingdom has been
      designed based on United States trial evidence. However, our understanding of
      acceptability and reasons for lung screening uptake or decline in a United
      Kingdom nontrial context are currently limited. OBJECTIVE: To explore with ever
      smokers the acceptability of targeted lung screening and uptake decision-making
      intentions. DESIGN: Qualitative study using semistructured focus groups and
      inductive thematic analysis to explore acceptability and uptake decision-making
      intentions with people of similar characteristics to lung screening eligible
      individuals. SETTING AND PARTICIPANTS: Thirty-three participants (22 ex-smokers;
      11 smokers) men and women, smokers and ex-smokers, aged 50-80 were recruited
      purposively from community and health settings in Manchester, England. RESULTS:
      Lung screening was widely acceptable to participants. It was seen as offering
      reassurance about lung health or opportunity for early detection and treatment.
      Participant's desire to know about their lung health via screening was impacted
      by perceived benefits; emotions such as worry about a diagnosis and screening
      tests; practicalities such as accessibility; and smoking-related issues including
      perceptions of individual risk and smoking stigma. DISCUSSION: Decision making
      was multifaceted with indications that current smokers faced higher participation
      barriers than ex-smokers. Reducing participation barriers through careful service
      design and provision of decision support information will be important in lung
      screening programmes to support informed consent and equitable uptake.

PMID- 30289582
TI  - Efficacy of liquid-based genetic diagnosis of endometrial cancer.
AB  - Although liquid-based cytology (LBC) has increased the sensitivity of cytological
      diagnosis of endometrial cancer (EC) compared with conventional smear cytology,
      the sensitivity of LBC for the detection of EC is between 70% and 96% and remains
      unsatisfactory. In the present study, we compared the efficacy of LBC with liquid
      based genetic diagnosis (LBGDx) by amplicon sequencing of five genes including
      PTEN, PIK3CA, CTNNB1, KRAS, and TP53 in 48 LBC subjects who underwent endometrial
      screening. Consequently, LBC classified 15 samples as "positive or suspicious for
      malignancy" and the 15 were later confirmed as EC. However, LBC failed to
      identify five cases who were diagnosed as EC by additional transvaginal
      ultrasound and endometrial curettage, indicating that the sensitivity of cytology
      alone was 75% (15/20). LBGDx identified 11 pathogenic PTEN variants in 10
      subjects, six PIK3CA variants in nine, three CTNNB1 variants in five, two KRAS
      variants in four, and three TP53 variants in three. Collectively, at least one
      pathogenic variant was identified in 19 subjects, which included 17 EC (15
      endometrioid carcinoma and 2 endometrial carcinosarcomas), and one cervical
      adenocarcinoma. However, LBGDx did not identify any pathogenic mutations in three
      of the 20 EC, indicating that the sensitivity of LBGDx alone was 85% (17/20).
      Although five EC were negative for malignancy by LBC and three were negative for
      pathogenic mutations by LBGDx, the combination of LBC and LBGDx would
      successfully diagnose all 20 EC. These data suggested that LBGDx is a useful
      strategy to improve the sensitivity of screening of EC by LBC.

PMID- 30289584
TI  - Diffusion of advanced medical imaging technology, CT, and MRI scanners, in Iran:
      A qualitative study of determinants.
AB  - BACKGROUND: Low-income and middle-income countries have a lot of problems in
      providing the financial, human, and capital resources for advanced medical
      imaging technologies (AMITs). Proper distribution of such expensive equipment
      might increase access to these services and enhance the quality and efficiency of
      health care. The present study aimed to identify the factors affecting the
      diffusion of AMITs including CT and MRI in Iran. METHODS: This is a qualitative
      research conducted in 2017. A number of purposively chosen policy makers and
      managers from Ministry of Health, medical universities, hospitals, health
      insurance, and vendor companies were approached for face-to-face and
      semistructured interviews. Data analysis was done using thematic analysis method.
      RESULTS: Three categories of influential factors were identified, including
      contextual, stakeholder related, and situational factors. With regards to the
      stakeholders, the ministry and physicians played the most important role in the
      diffusion process of the AMITs. Health insurance organizations and vendor
      companies played a minor role in distribution of the equipment. Application of
      political pressure by the authorities on the Ministry of Health to issue licenses
      for the acquisition of AMITs was taken as the most important factor and the
      greatest challenge in the diffusion of devices. CONCLUSION: The results sought to
      assist health system authorities to manage diffusion of AMITs effectively and
      assign an equitable access to the expensive resources. The diffusion management
      together with utilization management could largely improve efficiency and cost
      containment. Medical technology diffusion management de facto needs policy
      instruments in both supply and demand sides.

PMID- 30289585
TI  - Development of an LC-MS/MS method for monitoring long term exposure to the
      parabens.
AB  - RATIONAL: Parabens, the alkyl esters of 4-hydroxybenzoic acid, are a family of
      compounds widely used as preservatives in cosmetic products, including for
      children, and some are permitted in foods. Parabens are known to be weak
      endocrine disruptor because they interfere with the function of endogenous
      hormones through binding to estrogen receptors. Therefore, the levels of parabens
      in biological samples indicate endocrine disruptive exposure. In particular, hair
      samples can provide information on accumulated exposure to parabens. METHODS: For
      monitoring of long term exposure to parabens, an improved analytical method for
      rapid and direct determination of parabens in hair sample was developed by ultra
      performance liquid chromatography-tandem mass spectrometry using on-line
      extraction. Five parabens (methyl-, ethyl-, propyl-, butyl-, and benzyl-paraben)
      were separated within 10 min after incubation with 1 N HCl. Parabens were
      separated using a Waters BEH C18 column (2.1 mm * 100 mm, 1.7 MUm) and a mobile
      phase consisting of 10 mM ammonium acetate in water and acetonitrile with a
      gradient program at a flow rate of 300 MUL/min. The analysis of the separated
      parabens was monitored with electrospray negative ionization tandem mass
      spectrometry (ESI/MS/MS). RESULTS: The linearities of the method was demonstrated
      by r2 >= 0.994. The limits of detection as defined by a signal to noise (S/N)
      ratio of 3 were 1 ~ 5 ng/g. The mean concentration of five parabens in human
      subjects hair was measured to be 55.6 +/- 24.3 ~ 136.9 +/- 48.5 ng/g.
      CONCLUSIONS: The levels of parabens in hair samples may play important role to
      understanding probable endocrine disruptive exposure, and the described method
      could be used to evaluate and monitor long term exposure of parabens as endocrine
      disruptor.

PMID- 30289586
TI  - Assessing performance of Taiwan hospitals using data envelopment analysis: In
      view of ownership.
AB  - With rapid economic development in Taiwan, people have greater awareness of
      health care and are paying more attention to it. From the perspective of hospital
      management, the scale of hospitals and efficiency improvement are of concern to
      hospital managers. However, the extent of efficiency will differ between public
      and private hospitals due to their different ownership and goals. The study aims
      to evaluate the efficiency of public and private hospitals and to investigate the
      influence of ownership on efficiency of hospitals. The differences between
      hospitals can be understood by analyzing the features of the organization of
      hospitals and their geographic environment. In this way, hospitals with
      relatively low efficiency will be able to make improvements based on concrete
      evidence. By means of the two-stage method, the efficiency scores of 182
      hospitals in Taiwan are compared. In the first stage, the data envelopment
      analysis is applied to obtain the efficiency scores of hospitals. The results
      show that private hospitals are more efficient than public hospitals. In the
      second stage, Tobit regression is used to investigate the factors influencing
      efficiency obtained by the data envelopment analysis. The results indicate that
      there are differences between ownership in market competition and the average
      length of stay.

PMID- 30289587
TI  - Predictors of mitochondrial DNA copy number and damage in a mercury-exposed rural
      Peruvian population near artisanal and small-scale gold mining: An exploratory
      study.
AB  - Mitochondrial DNA (mtDNA) copy number (CN) and damage in circulating white blood
      cells have been proposed as effect biomarkers for pollutant exposures. Studies
      have shown that mercury accumulates in mitochondria and affects mitochondrial
      function and integrity; however, these data are derived largely from experiments
      in model systems, rather than human population studies that evaluate the
      potential utility of mitochondrial exposure biomarkers. We measured mtDNA CN and
      damage in white blood cells (WBCs) from 83 residents of nine communities in the
      Madre de Dios region of the Peruvian Amazon that vary in proximity to artisanal
      and small-scale gold mining. Prior research from this region reported high levels
      of mercury in fish and a significant association between food consumption and
      human total hair mercury level of residents. We observed that mtDNA CN and damage
      were both associated with consumption of fruit and vegetables, higher diversity
      of fruit consumed, residential location, and health characteristics, suggesting
      common environmental drivers. Surprisingly, we observed negative associations of
      mtDNA damage with both obesity and age. We did not observe any association
      between total hair mercury or, in contrast to previous results, age, with either
      mtDNA damage or CN. The results of this exploratory study highlight the
      importance of combining epidemiological and laboratory research in studying the
      effects of stressors on mitochondria, suggesting that future work should
      incorporate nutritional and social characteristics, and caution should be taken
      when applying conclusions from epidemiological studies conducted in the developed
      world to other regions, as results may not be easily translated. 2018 Wiley
      Periodicals, Inc.

PMID- 30289588
TI  - White matter microstructure in fetal alcohol spectrum disorders: A systematic
      review of diffusion tensor imaging studies.
AB  - Diffusion tensor imaging (DTI) has revolutionized our understanding of the neural
      underpinnings of alcohol teratogenesis. This technique can detect alterations in
      white matter in neurodevelopmental disorders, such as fetal alcohol spectrum
      disorder (FASD). Using Prisma guidelines, we identified 23 DTI studies conducted
      on individuals with prenatal alcohol exposure (PAE). These studies confirm the
      widespread nature of brain damage in PAE by reporting diffusivity alterations in
      commissural, association, and projection fibers; and in relation to increasing
      cognitive impairment. Reduced integrity in terms of lower fractional anisotropy
      (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) is reported
      more consistently in the corpus callosum, cerebellar peduncles, cingulum, and
      longitudinal fasciculi connecting frontal and temporoparietal regions. Although
      these interesting results provide insight into FASD neuropathology, it is
      important to investigate the clinical diversity of this disorder for better
      treatment options and prediction of progression. The aim of this review is to
      provide a summary of different patterns of neural structure between PAE and
      typically developed individuals. We further discuss the association of
      alterations in diffusivity with demographic features and symptomatology of PAE.
      With the accumulated knowledge of the neural correlates of FASD presenting
      symptoms, a comprehensive understanding of the heterogeneity in FASD will
      potentially improve the disease management and will highlight the diagnostic
      challenges and potential areas of future research avenues, where neural markers
      may be beneficial.

PMID- 30289589
TI  - Heterolysis of Dihydrogen by Nucleophilic Calcium Alkyls.
AB  - beta-Diketiminato (BDI) calcium alkyl derivatives undergo hydrogenolysis with H2
      to regenerate [(BDI)CaH]2 , allowing the catalytic hydrogenation of a wide range
      of 1-alkenes and norbornene under very mild conditions (2 bar H2 , 298 K). The
      reactions are deduced to take place with the retention of the dimeric structures
      of the calcium hydrido-alkyl and alkyl intermediates via a well-defined sequence
      of Ca-H/C=C insertion and Ca-C hydrogenation events. This latter deduction is
      strongly supported by DFT calculations (B3PW91) performed on the 1-hexene/H2
      system, which also indicates that the hydrogenation transition states display
      features which discriminate them from a classical sigma-bond metathesis
      mechanism. In particular, NBO analysis identifies a strong second order
      interaction between the filled alpha-methylene sp3 orbital of the n-hexyl chain
      and the sigma* orbital of the H2 molecule, signifying that the H-H bond is broken
      by what is effectively the nucleophilic displacement of hydride by the organic
      substituent.

PMID- 30289590
TI  - User involvement in digital health: Working together to design smart home health
      technology.
AB  - BACKGROUND: Public involvement adds value to numerous aspects of health research,
      yet few studies have attempted to evaluate its impact on research. Evidence of
      such impact is needed to develop recommendations for best practice and ensure
      adequate resourcing. AIM: To evaluate public involvement within a large
      interdisciplinary Science, Technology, Engineering and Mathematics (STEM)
      research project that focused on digital health. METHODS: The evaluation was
      conducted with members of the project's Public Advisory Groups (PAG) and with
      researchers who had participated in involvement activities. Two questionnaires
      were designed based on a public involvement value systems and clusters framework.
      RESULTS: Responses from members of the PAG (n = 10) were mostly positive towards
      normative values, which include moral, ethical and political aspects of
      involvement in research, and towards values concerning the conduct of public
      involvement and best practices. Researchers' responses (n = 16) indicated they
      felt that involvement was generally effective and increased the quality,
      relevance and generalizability of their work. However, their responses about the
      validity of involvement in research were varied. They also highlighted several
      challenges including how well public involvement impacted on research, how
      decisions made in the research might differ from the views generated from public
      involvement, and barriers to researchers' participation. DISCUSSION AND
      CONCLUSION: Our evaluation suggests that members of the public and the
      researchers value involvement. However, there is a need to consider how to embed
      public involvement to an even greater extent in STEM contexts and a need to
      address any barriers for researchers' own involvement.

PMID- 30289591
TI  - Effect of preparation design on marginal and internal adaptation of translucent
      zirconia laminate veneers.
AB  - This study investigated the effect of preparation design on the marginal and
      internal adaptation of laminate veneers (LVs) fabricated from translucent
      zirconia. Thirty-three resin teeth were prepared for LVs of three designs: window
      preparation (WP); incisal shoulder preparation (ISP); and incisal palatal chamfer
      preparation (IPP). Marginal adaptation was evaluated by measuring the vertical
      discrepancy between the LV margin and the finish line at 60 points. The internal
      adaptation was assessed by measuring the internal space width as the distance
      between the LV and the tooth at cervical, central, and incisal sites after
      sectioning. At the incisal, mesial, and distal sites, mean marginal discrepancies
      were significantly lower in the WP group than in the other two groups; the IPP
      group had the highest marginal discrepancies. At incisal sites, the median
      internal space was significantly higher in the IPP group than in the WP and ISP
      groups and higher in the ISP group than in the WP group. At the incisal site,
      marginal and internal adaptations were better for the non-overlap translucent
      zirconia LV design (WP) than for the overlap designs (ISP and IPP). The
      characteristics of the translucent zirconia LVs used in the present study
      indicate acceptable clinical performance.

PMID- 30289592
TI  - Coproduction and health: Public and clinicians' perceptions of the barriers and
      facilitators.
AB  - BACKGROUND: Coproduction is an approach increasingly recognized across public
      services internationally. However, awareness of the term and the barriers and
      facilitators to its implementation in the NHS are not widely understood. This
      study examines clinician and public perceptions of coproduction within the
      context of the Prudent Healthcare initiative. OBJECTIVES: To provide insights
      into how coproduction is viewed by clinicians and the public and identify
      perceived barriers and facilitators to its implementation. DESIGN: Using
      qualitative research methods, interviews were conducted with the public (n = 40)
      and clinicians (n = 40). Five focus groups were also conducted with the public (n
      = 45) and six focus groups with clinicians (n = 26). The COM-B model was used to
      analyse the data; key domains include Capability, Opportunity and Motivation.
      SETTING: This is an all-Wales study, involving six Health Boards, an NHS trust
      and community and patient groups. RESULTS: Key barriers relating to Capability
      include lack of awareness of the term coproduction and inadequate communication
      between clinicians and citizens. Opportunity-centred barriers include service and
      time constraints. Conversely, facilitators included utilizing partnerships with
      community organizations. Motivation-related barriers included preconceptions
      about patients' limitations to coproduce. CONCLUSIONS: There were broadly
      positive perceptions among participants regarding coproduction, despite initial
      unfamiliarity with the term. Despite study limitations including
      underrepresentation of employed public participants and junior doctors, our
      analysis may assist researchers and policymakers who are designing, implementing
      and evaluating interventions to promote coproduction.

PMID- 30289593
TI  - Hydroxyapatite/collagen coating on PLGA electrospun fibers for osteogenic
      differentiation of bone marrow mesenchymal stem cells.
AB  - The architecture and composition of bone tissue engineering scaffolds play
      important roles in modulating the growth of bone tissue. Composite fibers
      composed of poly(lactic-co-glycolic acid) (PLGA) skeleton coated with
      hydroxyapatite (HA) or hydroxyapatite/collagen (HA/Col) were successfully
      produced via electrospinning, biomimetic process, and adsorption. The PLGA
      skeleton fabricated by electrospinning process with a nanofibrous structure
      (diameter ranging from 200 to 400 nm) showed a morphologic similarity to the
      extracellular matrix (ECM). SEM, EDX, and XRD analysis confirmed the presence of
      HA and Col on the composite fibers. Mesenchymal stem cells were used to evaluate
      the cellular behaviors including cell attachment and spreading, proliferation,
      and osteogenic differentiation on these fibers (PLGA, PLGA/HA, and PLGA/HA/Col).
      The results demonstrated that the HA and HA/Col coating improved the interaction
      between mesenchymal stem cells and the composite fibers reflected by accelerated
      cell spreading, increased alkaline phosphatase (ALP) activity and enhanced
      expression of osteogenic-related genes. The HA/Col coating was more effective in
      improving this interaction compared with HA coating. The PLGA/HA/Col composite
      fibers may be promising as a candidate scaffold for bone tissue engineering. (c)
      2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2863-2870, 2018.

PMID- 30289594
TI  - Haploinsufficiency of NCOR1 associated with autism spectrum disorder, scoliosis,
      and abnormal palatogenesis.
AB  - NCOR1 (nuclear receptor corepressor 1) is a transcriptional coregulatory protein
      that regulates the balance between histone acetylation and histone deacetylation.
      NCOR1 is listed as one of the 3,230 dose-sensitive genes which very rarely show
      truncating mutations in the pediatric population without severe diseases, even in
      a heterozygous state. In a large cohort study of intellectual disability/autism
      spectrum disorder, splicing mutations were identified in two individuals,
      however, the truncating effects of these splicing mutations have not been
      examined at the transcription level. We describe a 3-year-old girl who had
      behavior consistent with autism spectrum disorder, a bifid uvula, and early-onset
      scoliosis. Trio exome analysis showed a de novo heterozygous mutation at the
      splice donor site in exon 19 of NCOR1, c.2182 + 1G > T (NM_00190440.1). Reverse
      transcription polymerase chain reaction assay confirmed that the splicing
      mutation results in skipping of exon 19, a shift in the reading frame and then to
      nonsense-mediated mRNA decay. This patient represents the first patient who has
      had unequivocal documentation of haploinsufficient for the NCOR1 gene. Based on
      our observations, we conclude that NCOR1 is indeed a human disease-causing gene.
      We further suggest that bifid uvula, a micro form of cleft palate, may well be
      causally related to de novo NCOR1 haploinsufficiency, in that a previously
      reported deletion mapping study of atypical Smith-Magenis syndrome patients with
      large deletions and cleft palate identified that NCOR1, the only loss-of-function
      intolerant gene within the region, is located in the smallest region of overlap.

PMID- 30289595
TI  - Mosaic KRAS mutation in a patient with encephalocraniocutaneous lipomatosis and
      renovascular hypertension.

PMID- 30289596
TI  - Preliminary observations of mitochondrial dysfunction in Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is a complex multisystem disorder because of errors
      in genomic imprinting with severe hypotonia, decreased muscle mass, poor
      suckling, feeding problems and failure to thrive during infancy, growth and other
      hormone deficiency, childhood-onset hyperphagia, and subsequent obesity.
      Decreased energy expenditure in PWS is thought to contribute to reduced muscle
      mass and physical activity but may also relate to cellular metabolism and
      disturbances in mitochondrial function. We established fibroblast cell lines from
      six children and adults with PWS and six healthy controls for mitochondrial
      assays. We used Agilent Seahorse XF extracellular flux technology to determine
      real-time measurements of several metabolic parameters including cellular
      substrate utilization, Adenosine Triphosphate (ATP)-linked respiration, and
      mitochondrial capacity in living cells. Decreased mitochondrial function was
      observed in the PWS patients compared to the healthy controls with significant
      differences in basal respiration, maximal respiratory capacity, and ATP-linked
      respiration. These results suggest disturbed mitochondrial bioenergetics in PWS
      although the low number of studied subjects will require a larger subject
      population before a general consensus can be reached to identify if mitochondrial
      dysfunction is a contributing factor in PWS.

PMID- 30289597
TI  - Effect of hydroxyapatite nanoparticles and wedelolactone on osteoblastogenesis
      from bone marrow mesenchymal stem cells.
AB  - Regenerative medicine has a high demand for the development of scaffold materials
      combined with other osteogenic inducers to generate bioactive composite materials
      for bone replacement therapies. Previously, we reported that wedelolactone
      promoted osteoblastogenesis of bone marrow mesenchymal stem cells (BMSCs). In
      this study, the effect of hydroxyapatites (HAps), bone composite materials we
      prepared, and the combined effect of wedelolactone and HAps on osteoblastogenesis
      differentiation was first evaluated. Three kinds of HAps constructed by a rod
      like shape with particle size of 25 nm (HAp-1), 37 nm (HAp-2), and 33 nm (HAp-3)
      did not affect BMSC survival, but induced activity of alkaline phosphatase(ALP),
      a marker enzyme for osteoblastogenesis. HAp-1 treatment resulted in a more
      significant increase in the number of ALP staining-positive BMSC, and maintained
      an extended time for the increased number of ALP staining-positive BMSC.
      Moreover, HAp-1 combined with wedelolactone induced a higher ALP activity for a
      longer time than HAp-2 and HAp-3, and also increased the bone mineralization
      level. Osteoblastogenesis-related marker genes expression including osteorix,
      osteocalcin, and runx2 were increased after BMSC were treated with HAp-1 for 6
      days. Although three kinds of HAps treatment for 9 days increased osteorix mRNA
      expression, osteocalcin, and runx2 mRNA expression levels were upregulated only
      by HAp-1. Similarly, only HAp-1 enhanced wedelolactone-induced osteocalcin,
      osteorix, and runx2 mRNA expression after 9 days treatment. Together, these
      results suggested that HAps with different sizes generated different effect on
      osteoblastogenesis. HAp-1 combined with wedelolacone can exert an enhanced effect
      on osteoblastogenesis, which has potential for treating osteoporosis. (c) 2018
      Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 145-153, 2019.

PMID- 30289598
TI  - Electrospun PCL/keratin/AuNPs mats with the catalytic generation of nitric oxide
      for potential of vascular tissue engineering.
AB  - Nitric oxide (NO)-generating materials are beneficial for vascular tissue
      engineering (VTE) scaffold because the produced NO would enhance endothelial
      cells viability while inhibit smooth muscle cell (SMC) proliferation and reduce
      platelet adhesion, resulting in ideal hemocompatibility and endothelialization.
      Herein, poly(epsilon-caprolactone) (PCL)/keratin biocomposite mats were first
      fabricated, followed by in situ gold (Au) nanoparticles loading to afford
      PCL/keratin/AuNPs mats. These mats were characterized using field emission
      scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), X
      ray diffraction (XRD), and thermogravimetric analysis (TGA). The
      PCL/keratin/AuNPs mats were demonstrated to be capable of catalyzing NO release
      in the mimicked blood microenvironments. The generated NO could enhance human
      umbilical vein endothelial cell growth and inhibit human umbilical arterial SMC
      viability. In addition, these mats maintained the antibacterial activity of Au
      nanoparticles with good blood compatibility. Taken together, these keratin-based
      composite mats have potential usage in the VTE. (c) 2018 Wiley Periodicals, Inc.
      J Biomed Mater Res Part A: 106A: 3239-3247, 2018.

PMID- 30289599
TI  - Copy number variants in hypoplastic right heart syndrome.
AB  - Hypoplastic right heart syndrome (HRHS) is a rare congenital defect characterized
      by underdeveloped and malformed structures of the right heart. Familial
      recurrence of HRHS indicates genetic factors contribute to its etiology. Our
      study investigates the presence of copy number variants (CNVs) in HRHS cases. We
      genotyped 42 HRHS cases identified from live births throughout California (2003
      2010) using the Illumina HumanOmni2.5-8 array. We identified 14 candidate CNVs in
      14 HRHS cases (33%) based on the genes included in the CNVs and their functions.
      Duplications overlapping part of ERBB4 were identified in two unrelated cases.
      ERBB4 is a neuregulin receptor with a pivotal role in cardiomyocyte
      differentiation and heart development. We also described a 7.5 Mb duplication at
      16q11-12. Multiple genes in the duplicated region have previously been linked to
      heart defects and cardiac development, including RPGRIP1L, RBL2, SALL1, and
      MYLK3. Of the 14 validated CNVs, we identified four CNVs in close proximity to
      genes linked to the Wnt signaling pathway. This study expands on our previous
      work supporting the role of genetics in HRHS. We identified CNVs affecting
      crucial genes and signaling pathways involved in right heart development. ERBB4
      and duplication of the 16q11-12 region are important areas for future
      investigation.

PMID- 30289600
TI  - The characteristics of temper outbursts in Prader-Willi syndrome.
AB  - The purpose of this study was to develop a comprehensive understanding of temper
      outbursts in Prader-Willi syndrome (PWS). A survey was developed from interviews
      conducted with individuals with PWS and their caregivers. The survey was
      completed by 101 primary caregivers. The findings suggest that outburst frequency
      decreases with age while duration increases. Adolescents exhibited more severe
      behaviors than children or adults. No differences were found across gender or
      genetic subtype. Provocations fit into three themes: goal blockage, social
      injustice, and difficulty dealing with change. Distracting the person or giving
      them space to calm down were the only management strategies judged effective.
      Risperidone, sertraline, and fluoxetine were the most common medications
      prescribed for outbursts, though parents reported only minor effects.

PMID- 30289601
TI  - Prenatal profile of Pallister-Killian syndrome: Retrospective analysis of 114
      pregnancies, literature review and approach to prenatal diagnosis.
AB  - Pallister-Killian syndrome (PKS) is a tissue limited mosaic disorder,
      characterized by variable degrees of neurodevelopmental delay and intellectual
      disability, typical craniofacial findings, skin pigmentation anomalies and
      multiple congenital malformations. The wide phenotypic spectrum of PKS in
      conjunction with the mosaic distribution of the i(12p) makes PKS an
      underdiagnosed disorder. Recognition of prenatal findings that should raise a
      suspicion of PKS is complicated by the fragmentation of data currently available
      in the literature and challenges in diagnosing a mosaic diagnosis on prenatal
      testing. Ultrasound anomalies, especially congenital diaphragmatic hernia,
      congenital heart defects, and rhizomelic limb shortening, have been related to
      PKS, but they are singularly not specific and are not present in all affected
      fetuses. We have combined prenatal data from 86 previously published reports and
      from our cohort of 114 PKS probands (retrospectively reviewed). Summarizing this
      data we have defined a prenatal growth profile and identified markers of
      perinatal outcome which collectively provide guidelines for early recognition of
      the distinctive prenatal profile and consideration of a diagnosis of PKS as well
      as for management and genetic counseling.

PMID- 30289603
TI  - In memoriam James L. German, a pioneer in early human genetic research.

PMID- 30289602
TI  - Using microarray-based subtyping methods for breast cancer in the era of high
      throughput RNA sequencing.
AB  - Breast cancer is a highly heterogeneous disease that can be classified into
      multiple subtypes based on the tumor transcriptome. Most of the subtyping schemes
      used in clinics today are derived from analyses of microarray data from thousands
      of different tumors together with clinical data for the patients from which the
      tumors were isolated. However, RNA sequencing (RNA-Seq) is gradually replacing
      microarrays as the preferred transcriptomics platform, and although transcript
      abundances measured by the two different technologies are largely compatible,
      subtyping methods developed for probe-based microarray data are incompatible with
      RNA-Seq as input data. Here, we present an RNA-Seq data processing pipeline,
      which relies on the mapping of sequencing reads to the probe set target sequences
      instead of the human reference genome, thereby enabling probe-based subtyping of
      breast cancer tumor tissue using sequencing-based transcriptomics. By analyzing
      66 breast cancer tumors for which gene expression was measured using both
      microarrays and RNA-Seq, we show that RNA-Seq data can be directly compared to
      microarray data using our pipeline. Additionally, we demonstrate that the
      established subtyping method CITBCMST (Guedj et al., ), which relies on a 375
      probe set-signature to classify samples into the six subtypes basL, lumA, lumB,
      lumC, mApo, and normL, can be applied without further modifications. This
      pipeline enables a seamless transition to sequencing-based transcriptomics for
      future clinical purposes.

PMID- 30289604
TI  - Mutations in the tRNA methyltransferase 1 gene TRMT1 cause congenital
      microcephaly, isolated inferior vermian hypoplasia and cystic leukomalacia in
      addition to intellectual disability.

PMID- 30289605
TI  - Basan gets a new fingerprint: Mutations in the skin-specific isoform of SMARCAD1
      cause ectodermal dysplasia syndromes with adermatoglyphia.
AB  - Basan syndrome is an autosomal dominant ectodermal dysplasia (ED) with congenital
      adermatoglyphia, transient neonatal acral bullae, and congenital facial milia.
      Autosomal dominant adermatoglyphia (ADG) is characterized as adermatoglyphia with
      hypohidrosis. Recently mutations in the skin-specific isoform of the gene
      SMARCAD1 have been found in both syndromes. This report proposes to unify these
      two previously distinct ED, into one syndrome. We offer a new acronym: SMARCAD
      syndrome (SMARCAD1-associated congenital facial Milia, Adermatoglyphia, Reduced
      sweating, Contractures, Acral Bullae, and Dystrophy of nails). Sanger sequencing
      was performed on genomic DNA from a patient with Basan syndrome using primers
      designed to flank SMARCAD1. Sanger sequencing revealed a novel variant,
      NM_001254949.1:c.-10 + 2 T > G, in the donor splice site of exon 1 of the skin
      specific isoform. This variant and the other five previously reported variants in
      Basan syndrome and ADG are all within the same donor splice site. We conclude
      that Basan syndrome and ADG are on a phenotypic spectrum of a monogenic syndrome
      which is better described by the acronym SMARCAD syndrome.

PMID- 30289606
TI  - Suppressing inflammation and enhancing osteogenesis using novel CS-EC@Ca
      microcapsules.
AB  - The aim of this study was to investigate the suppression of inflammation and
      enhancement of osteogenesis using chitosan-coated calcium hydroxide-loaded
      microcapsules (CS-EC@Ca microcapsules) in vivo. Circular defects were created in
      the mandibular bones of rabbits and filled with Ca(OH)2 , Bio-oss, or CS-EC@Ca
      microcapsules, and rabbits without drug implantation served as the controls.
      Lipopolysaccharides were injected in situ daily in all groups for 7 days.
      Mandibular bones were investigated at 4 and 12 weeks after surgery using micro
      CT, histological observations, and real-time PCR analysis. At the postoperation,
      there was more substantial nascent bone in the microcapsule and Bio-oss groups
      than in the control group. The recovery of the rabbits in the Ca(OH)2 group was
      slower than the control group, as determined using micro-CT and histological
      staining. Osteocalcin and collagen type I production was not significantly
      different between the microcapsule and Bio-oss groups (p > 0.05), but the
      expression levels of the two molecules were significantly increased compared to
      the control and Ca(OH)2 groups at postoperation (p < 0.05). The mRNA transcript
      levels of inflammatory factors in the microcapsule group had the most reduced
      expression of IL-6 and TNF-alpha (p < 0.05). The microcapsules significantly
      reduced inflammation and promoted osteogenesis in this rabbit model of
      inflammatory bone destruction. Our findings indicate that CS-EC@Ca microcapsules
      hold potential for use in apical periodontitis treatment. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3222-3230, 2018.

PMID- 30289607
TI  - A de novo in-frame deletion of CASK gene causes early onset infantile spasms and
      supratentorial cerebral malformation in a female patient.
AB  - We report a female patient with a novel, heterozygous, de novo in-frame deletion
      in the CASK gene (c.2179-2181 del GTA, p.Val727del) who presents with early onset
      infantile spasms, hypsarrhythmia on electroencephalogram (EEG), and frontal lobe
      abnormalities on brain magnetic resonance imaging (MRI) without microcephaly and
      pontocerebellar hypoplasia. This is the first case report of an in-frame deletion
      in the CASK gene causing early onset infantile spasms and supratentorial focal
      brain malformation on brain MRI in the literature. This is also the first report
      of a female with CASK-related disorder with hypsarrhythmia pattern on EEG. This
      report expands the clinical phenotypic spectrum in CASK-related disorders in
      female patients. A heterozygous de novo variant in RORA (c.88 C>G, p.Gln 30Glu)
      was reported in this patient as a variant of uncertain significance.

PMID- 30289608
TI  - Stress and sleep remain significant predictors of health after controlling for
      negative affect.
AB  - Prior research has shown that the predictive power of a stress-health model can
      be improved by the addition of sleep as a predictor variable. However, negative
      affect (NA) may act as a confounding variable in stress-health relationships: a
      source of bias that potentially inflates the observed relationship between stress
      and health. The current study examines whether stress and sleep remain
      significant predictors of health after controlling for trait NA. An online survey
      containing well-established measures of stress, sleep, health, and NA was
      completed by 460 undergraduates. Hierarchical regression analyses revealed that
      stress and sleep remained significant predictors of self-reported health after
      controlling for the effects of NA. Our findings support the notion that stress
      health models can be improved by the integration of sleep as an additional
      predictor variable and demonstrate that the stress/sleep-health relationships are
      not fully explained by dispositional NA. From a theoretical perspective, the
      inclusion of NA measures allows researchers to tease apart the unique
      contributions of predictor variables. This knowledge can subsequently be put to
      the test with greater confidence in the design of interventions that seek to
      improve health through stress reduction and improved sleep.

PMID- 30289610
TI  - Morphological and isotopic changes of heterocystous cyanobacteria in response to
      N2 partial pressure.
AB  - Earth's atmospheric composition has changed significantly over geologic time.
      Many redox active atmospheric constituents have left evidence of their presence,
      while inert constituents such as dinitrogen gas (N2 ) are more elusive. In this
      study, we examine two potential biological indicators of atmospheric N2 : the
      morphological and isotopic signatures of heterocystous cyanobacteria. Biological
      nitrogen fixation constitutes the primary source of fixed nitrogen to the global
      biosphere and is catalyzed by the oxygen-sensitive enzyme nitrogenase. To protect
      this enzyme, some filamentous cyanobacteria restrict nitrogen fixation to
      microoxic cells (heterocysts) while carrying out oxygenic photosynthesis in
      vegetative cells. Heterocysts terminally differentiate in a pattern that is
      maintained as the filaments grow, and nitrogen fixation imparts a measurable
      isotope effect, creating two biosignatures that have previously been interrogated
      under modern N2 partial pressure (pN2 ) conditions. Here, we examine the effect
      of variable pN2 on these biosignatures for two species of the filamentous
      cyanobacterium Anabaena. We provide the first in vivo estimate of the intrinsic
      isotope fractionation factor of Mo-nitrogenase (epsilonfix  = -2.71 +/- 0.090/00)
      and show that, with decreasing pN2 , the net nitrogen isotope fractionation
      decreases for both species, while the heterocyst spacing decreases for Anabaena
      cylindrica and remains unchanged for Anabaena variabilis. These results are
      consistent with the nitrogen fixation mechanisms available in the two species.
      Application of these quantifiable effects to the geologic record may lead to new
      paleobarometric measurements for pN2 , ultimately contributing to a better
      understanding of Earth's atmospheric evolution.

PMID- 30289611
TI  - Norberto J. Palleroni (1922-2018).

PMID- 30289609
TI  - Insights on beta-blockers for the treatment of hypertension: A survey of health
      care practitioners.
AB  - A quantitative survey was completed by 103 primary care physicians (PCPs) and 59
      cardiologists who regularly prescribed beta-blockers to assess knowledge and use
      of this heterogeneous drug class for hypertension. More cardiologists than PCPs
      chose beta-blockers as initial antihypertensive therapy (30% vs 17%, P < 0.01).
      Metoprolol and carvedilol were the most commonly prescribed beta-blockers.
      Cardiologists rated "impact on energy" and "arterial vasodilation" as more
      important than PCPs (P < 0.05/<0.01, respectively). Awareness of vasodilation was
      greater for carvedilol (52%) than nebivolol (31%). Association between beta
      blockers and clinical variables included nebivolol with beta1 -selectivity,
      nebivolol and carvedilol with vasodilation and efficacy in older patients and
      African Americans, metoprolol with heart rate reduction, and atenolol and
      metoprolol with weight gain and hyperglycemia. Physicians preferred prescribing
      beta-blockers with lower risk of incident diabetes. Clinical practice guidelines
      influenced physician prescribing more than formularies or performance metrics.
      This survey captures physicians' perceptions/use of various beta-blockers and
      clinically relevant knowledge gaps.

PMID- 30289612
TI  - Risk of hepatic neoplasms in Wolf-Hirschhorn syndrome (4p-): Four new cases and
      review of the literature.
AB  - Wolf-Hirschhorn syndrome (WHS) is a rare contiguous gene deletion disorder
      characterized by distinctive craniofacial features, prenatal/postnatal growth
      deficiency, intellectual disability, and seizures. Various malformations of
      internal organs are also seen. Neoplasia has not been documented as a typical
      feature of WHS. We review the three prior reports of hepatic neoplasia in WHS and
      add four previously unreported individuals. We propose that, in the context of
      the rarity of WHS, these seven cases suggest that hepatocellular neoplasia may be
      a feature of WHS.

PMID- 30289613
TI  - Development of mechanically compliant 3D composite scaffolds for bone tissue
      engineering applications.
AB  - Cancellous bone region of the human native bone has the potential to bear
      significant mechanical loads. However, due to the following parameters such as
      low trabecular volume, more porosity, less thickness and more interconnectivity,
      cancellous bone is accessible to damage in accidents or when aging. This research
      led to the effective fabrication and engineering of cancellous region of the bone
      for its application in reconstruction or filling of bone voids after resection of
      large tumor mass. Scaffolds containing hydroxyapatite (HAp), polyvinyl alcohol
      (PVA) and polyvinyl pyrrolidone (PVP) (5% polymer and HAp concentrations) at
      different HAp: polymer composite ratios (50:50, 70:30 and 80:20), were fabricated
      by freeze-drying method using only water as solvent and ribose as crosslinker for
      the scaffolds. The fabricated scaffolds were characterized for its mechanical
      (compressive) strength, chemical properties using FT-IR and XRD analyses,
      swelling and degradation studies, confirmation of mineralization process by
      immersion in simulated body fluid (SBF) for 7, 15 and 30 days, morphological
      analysis using scanning electron microscopy (SEM), and biocompatibility
      properties by performing MTT analysis. From the combined interpretation of the
      above mentioned tests, it was proven that 80:20 ratio of HAp to polymers was
      found to be the most suitable scaffold in terms of its optimal properties for its
      use as bone graft material for trabecular bone. (c) 2018 Wiley Periodicals, Inc.
      J Biomed Mater Res Part A: 106A: 3267-3274, 2018.

PMID- 30289614
TI  - Dental and craniofacial characteristics caused by the p.Ser40Leu mutation in
      IFITM5.
AB  - Severe forms of osteogenesis imperfecta (OI) are usually caused by mutations in
      genes that code for collagen Type I and frequently are associated with
      craniofacial abnormalities. However, the dental and craniofacial characteristics
      of OI caused by the p.Ser40Leu mutation in the IFITM5 gene have not been
      reported. We investigated a 15-year-old girl with severe OI caused by this
      mutation. She had marked deformations of extremity long bones. There were no
      clinical or radiological signs of dentinogenesis imperfecta, but one tooth was
      missing and several teeth were impacted. Cone beam computed tomography revealed a
      generalized osteopenic appearance of the craniofacial skeleton, bilateral
      enlargement of mandibular bodies, and areas of cortical erosions. The cranial
      base and skull showed a generalized granular bone pattern with a mixture of
      osteosclerosis and osteolysis. Sphenoid and frontal sinuses were congenitally
      missing. Cephalometric analysis indicated a Class III growth pattern. In this
      case, the IFITM5 p.Ser40Leu mutation did not affect tooth structure but was
      associated with deformities in craniofacial bones that resemble those in the
      other parts of the skeleton.

PMID- 30289615
TI  - An additional patient with a homozygous mutation in DCPS contributes to the
      delination of Al-Raqad syndrome.
AB  - DCPS gene encodes for a protein involved in gene expression regulation through
      promoting cap degradation during mRNA decapping processes. Mutations altering the
      DCPS function have been associated to a distinct disorder, Al-Raqad syndrome, so
      far described only in two families. We report on a patient harboring a novel
      homozygous missense mutation in DCPS, presenting with growth retardation,
      craniofacial anomalies, skin dyschromia, and neuromuscular defects. This case
      study explains the molecular spectrum of DCPS mutations and might contribute to
      the phenotypic delineation of this rare condition.

PMID- 30289616
TI  - Photoluminescent arginine-functionalized polycitrate with enhanced cell activity
      and hemocompatibility for live cell bioimaging.
AB  - Development of biodegradable and highly biocompatible polymer with intrinsical
      photoluminescence and high photostability for real-time live cell bioimaging has
      attracted much attention recently. Here, a biodegradable and amphiphilic poly
      (citrate)-co-poly (ethylene glycol) (PEG) grafted with arginine (PCGA) polymer
      with intrinsical fluorescence was synthesized for targeted live cell bioimaging.
      The physicochemical structure, photoluminescent properties, hemocompatibility,
      cytotoxicity, and fluorescent bioimaging studies in live cells were determined in
      detail. PCGA showed a significantly high hemocompatibility, low cytotoxicity, and
      excellent photostability, which allows for imaging the live cells attachment and
      proliferation. Furthermore, PCGA could efficiently enhance cell attachment and
      proliferation due to the presence of arginine, suggesting their high cellular
      biocompatibility. Importantly, PCGA could selectively stain the lysosome in
      cells. Our results demonstrated that the amino acid-based polymer
      functionalization may be an important strategy to develop multifunctional
      biomaterials with enhanced biocompatibility for targeted bioimaging, cancer
      therapy, and regenerative medicine. (c) 2018 Wiley Periodicals, Inc. J Biomed
      Mater Res Part A: 106A: 3175-3184, 2018.

PMID- 30289617
TI  - Tuberculosis in dialysis: Clinical spectrum and outcome from an endemic region.
AB  - INTRODUCTION: Tuberculosis (TB) is a significant health problem in developing
      countries. There are limited data on TB among end stage renal disease (ESRD)
      patients on maintenance dialysis in India. Clinical profile and outcome of TB in
      dialysis were studied. METHODS: Retrospective study of ESRD patients who were on
      maintenance dialysis (either peritoneal dialysis [PD] or hemodialysis (HD]) and
      diagnosed to have TB over a period of 11 years. FINDINGS: Thirty-two patients had
      a diagnosis of TB. Mean age of the patients was 50.3 +/-13.9 years. The majority
      (56.2%) of the patients were female. The modality of dialysis was HD in 53.1% and
      PD in 46.9%. Mean duration of dialysis at the diagnosis of TB was 15.1 +/- 13.9
      months. Over three-quarter of the patients had an extrapulmonary involvement.
      Pleuro-pulmonary (40.6%), peritoneum (34.4%), and lymph node (15.6%) were the
      most common sites for TB. About 6.3%patients had disseminated TB, and 3.1% had
      pericardial TB. The clinical presentation of TB was: fever/pyrexia of unknown
      origin 28.1%, constitutional symptoms of anorexia, fever, night sweats and weight
      loss 34.4%, abnormal chest radiograph 37.5%, ascites/peritonitis 34.4%, pleural
      effusion 25%, lymphadenopathy 18.8%, meningoencephalitis 6.3%, and pericardial
      effusion 3.1%. Peritoneal TB presented as nonresolving peritonitis in PD and
      ascites in HD. The diagnosis was a microbiological/histological in 50% and rest
      50% only on clinical grounds. Nine (29%) patients had adverse effects of anti-TB
      drugs. Four patients of TB peritonitis had a poor gastrointestinal tolerance of
      anti-TB drugs and defaulted on the treatment and had an adverse outcome. About
      53.1% of the patients survived, and 46.9% died. DISCUSSION: TB in dialysis is
      mostly extrapulmonary. Early diagnosis is difficult, and the adverse effects of
      anti-TB medications complicate the treatment. TB in dialysis carries high
      morbidity and mortality. TB peritonitis has a poor prognosis.

PMID- 30289618
TI  - HMGA2 as a functional antagonist of PARP1 inhibitors in tumor cells.
AB  - Poly(ADP-ribose) polymerase 1 inhibitors alone or in combination with DNA
      damaging agents are promising clinical drugs in the treatment of cancer. However,
      there is a need to understand the molecular mechanisms of resistance to PARP1
      inhibitors. Expression of HMGA2 in cancer is associated with poor prognosis for
      patients. Here, we investigated the novel relationship between HMGA2 and PARP1 in
      DNA damage-induced PARP1 activity. We used human triple-negative breast cancer
      and fibrosarcoma cell lines to demonstrate that HMGA2 colocalizes and interacts
      with PARP1. High cellular HMGA2 levels correlated with increased DNA damage
      induced PARP1 activity, which was dependent on functional DNA-binding AT-hook
      domains of HMGA2. HMGA2 inhibited PARP1 trapping to DNA and counteracted the
      cytotoxic effect of PARP inhibitors. Consequently, HMGA2 decreased caspase 3/7
      induction and increased cell survival upon treatment with the alkylating methyl
      methanesulfonate alone or in combination with the PARP inhibitor AZD2281
      (olaparib). HMGA2 increased mitochondrial oxygen consumption rate and spare
      respiratory capacity and increased NAMPT levels, suggesting metabolic support for
      enhanced PARP1 activity upon DNA damage. Our data showed that expression of HMGA2
      in cancer cells reduces sensitivity to PARP inhibitors and suggests that
      targeting HMGA2 in combination with PARP inhibition may be a promising new
      therapeutic approach.

PMID- 30289619
TI  - Insistence on sameness and broader autism phenotype in simplex families with
      autism spectrum disorder.
AB  - Insistence on sameness (IS) in individuals with autism spectrum disorder (ASD)
      and their families may have utility in identifying meaningful subgroups for
      studying the pathophysiological and genetic pathways affected in ASD. The primary
      objectives of the current study were to (1) characterize features of IS in
      parents of children with ASD and (2) examine their relationships with child IS
      symptoms. Participants were 2760 families who participated in the Simons Simplex
      Collection. Levels of parent IS were measured using the Broader Autism Phenotype
      Questionnaire (BAPQ). A factor analysis generated a BAPQ-IS scale, consisting of
      a subset of 11 items from the original BAPQ-Rigid scale. Correlations were run to
      examine the relationship between parent BAP and child IS variables. Correlations
      were found between parent IS and measures of child IS. Although relationships
      between parent and child IS features were statistically significant in this large
      sample, effect sizes were small. Results may be reflective of sample design that
      only included simplex families, where ASD severity may be predominantly driven by
      spontaneous mutations and less by common inherited risk from parents. In
      addition, child and parent measures used may have differentially captured
      features and severity of IS. Further research is needed on how IS can be
      accurately measured throughout development and across individuals with ASD and
      their unaffected family members to facilitate future studies on IS as a possible
      endophenotype for ASD. Autism Res 2018, 11: 1253-1263. (c) 2018 International
      Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Previous
      research has suggested that insistence on sameness (IS) may be a heritable trait
      in autism spectrum disorder (ASD). The study examined whether children with high
      levels of IS had parents with IS tendencies. A small relationship was found
      between parent and child measures of IS. Future research is needed on measurement
      of insistence on sameness across individuals with and without ASD to further
      examine this relationship and improve understanding of the genetics of ASD.

PMID- 30289620
TI  - In Situ Gluten-Chitosan Interlocked Self-Assembled Supramolecular Architecture
      Reduces T-Cell-Mediated Immune Response to Gluten in Celiac Disease.
AB  - SCOPE: The prevalence of celiac disease has increased since the last half of the
      20th century and is now about 1% in most western populations. At present, people
      who suffer from celiac disease have to follow a gluten-exclusion diet throughout
      their lives. Compliance to this restrictive diet is demanding and the development
      of alternative strategies has become urgent. METHODS AND RESULTS: In this
      context, it is found that the biocompatible aminopolysaccharide chitosan imposes
      a different gluten reorganization after gluten redox reaction producing in situ
      mechanically interlocked supramolecular assemblies between gluten and chitosan.
      These new structures result in the decrease of gluten digestibility, tissue
      transglutaminase deamidation activity, and interferon-gamma production in
      intestinal T cell lines generated from biopsy specimens of celiac disease
      patients. CONCLUSION: Overall, the results demonstrate the potential of this
      research avenue to celiac disease is problematic, as the reorganization of gluten
      proteins to a novel supramolecular architecture shows a positive impact on known
      pathogenesis mechanisms of the disease. At present, the only therapy for celiac
      disease is adherence to a gluten-free diet. Here, it is shown that chitosan
      imposed gluten reorganization to an interlocked self-assembled supramolecular
      architecture reduces gluten digestibility, R5-reactivity, tissue transglutaminase
      deamidation activity, and its capacity to stimulate a T-cell-mediated immune
      response in celiac disease.

PMID- 30289621
TI  - Measuring costs and quality of life for venous leg ulcers.
AB  - Venous leg ulcers (VLUs) result in substantial economic costs and reduced quality
      of life (QoL); however, there are few Australian cost estimates, especially using
      patient-level data. We measured community-setting VLU management costs and the
      impact on the QoL of affected individuals. VLU patients were recruited from a
      specialist wound clinic, an outpatient clinic, and two community care clinics in
      Queensland. Cost data were collected at the baseline visit. QoL (EQ-5D-5L) and
      wound status data were collected at baseline, 1, 3, and 6 months. Patients were
      classified into guideline-based/optimal care and usual care groups. Average
      weekly costs per patient were statistically significantly different between the
      usual care and optimal care groups-$214.61 and $294.72, respectively (P = 0.04).
      Baseline average QoL score for an unhealed ulcer was significantly higher in the
      optimal care group compared with usual care (P = 0.025). Time to healing differed
      between the usual care group and the optimal care group (P = 0.04), with averages
      of 3.9 and 2.7 months, respectively. These findings increase the understanding of
      the costs, QoL, and healing outcomes of VLU care. Higher optimal care costs may
      be offset by faster time to healing. This study provides data to inform an
      economic evaluation of guideline-based care for VLUs.

PMID- 30289622
TI  - The birth prevalence, severity, and temporal trends of congenital heart disease
      in the middle-income country: A population-based study.
AB  - OBJECTIVES: There is limited data on congenital heart disease (CHD) from the
      lower- and middle-income country. We aim to study the epidemiology of CHD with
      the specific objective to estimate the birth prevalence, severity, and its trend
      over time. DESIGN: A population-based study with data retrieved from the
      Pediatric Cardiology Clinical Information System, a clinical registry of acquired
      and congenital heart disease for children. SETTING: State of Johor, Malaysia.
      PATIENTS: All children (0-12 years of age) born in the state of Johor between
      January 2006 and December 2015. INTERVENTION: None. OUTCOME MEASURE: The birth
      prevalence, severity, and temporal trend over time. RESULTS: There were 531,904
      live births during the study period with 3557 new cases of CHD detected.
      Therefore, the birth prevalence of CHD was 6.7 per 1000 live births (LB) (95%
      confidence interval [CI]: 6.5-6.9). Of these, 38% were severe, 15% moderate, and
      47% mild lesions. Hence, the birth prevalence of mild, moderate, and severe CHD
      was 3.2 (95% CI: 3.0-3.3), 0.9 (95% CI: 0.9- 1.1), and 2.6 (95% CI: 2.4-2.7) per
      1000 LB, respectively. There was a significant increase in the birth prevalence
      of CHD, from 5.1/1000 LB in 2006 to 7.8/1000 LB in 2015 (P < .0001) due to
      increase in detection of both mild (1.9/1000 LB in 2006 to 3.9/1000 LB in 2015, P
      < .001) and severe CHD (1.8/1000 LB in 2005 to 2.9/1000 LB in 2015, P < .001).
      CONCLUSIONS: The birth prevalence of CHD was 6.7 per 1000 live births, and two in
      five were severe and significantly associated with syndrome and extracardiac
      defect. There was a significant increase in the detection of severe lesions in
      recent years leading to more burden to resources that are already limited in the
      middle-income country. Therefore, strategic and comprehensive pediatric and
      congenital heart surgery program is required.

PMID- 30289623
TI  - Application of solid-phase microextraction in current biomedical research.
AB  - Extraction of endogenous compounds and drugs and their corresponding metabolites
      from complex matrices, such as biofluids and solid tissues, requires adequate
      analytical approach facilitating qualitative and quantitative analysis. To this
      end, solid-phase microextraction has been introduced as modern technology that is
      capable of efficient and high-throughput extraction of compounds due to its
      ability to amalgamate sampling, extraction, and pre-concentration steps, while
      requiring minimal use of organic solvents. The ability of solid-phase
      microextraction to enable analyses on small-volume biological samples and growing
      availability of biocompatible solid-phase microextraction coatings make it a
      highly useful technology for variety of applications. For example, solid-phase
      microextraction is particularly useful for identifying biomarkers in metabolomics
      studies, and it can be successfully applied in pharmaceutical and toxicological
      studies requiring the fast and sensitive determination of drug levels, especially
      those that are present at low levels in biological matrices such as plasma,
      urine, saliva, and hair. Moreover, solid-phase microextraction can be directly
      applied in in vivo studies because this extraction technique is non-exhaustive
      and its biocompatible probes offer minimal invasiveness to the analyzed system.
      In this article, we review recent progress in well-established solid-phase
      microextraction technique for in vitro and in vivo analyses of various
      metabolites and drugs in clinical, pharmaceutical, and toxicological
      applications.

PMID- 30289624
TI  - A prediction tool for hospital-acquired pressure ulcers among surgical patients:
      Surgical pressure ulcer risk score.
AB  - Surgical patients are prone to developing hospital-acquired pressure ulcers
      (HAPU). Therefore, a better prediction tool is needed to predict risk using
      preoperative data. This study aimed to determine, from previously published HAPU
      risk factors, which factors are significant among our surgical population and to
      develop a prediction tool that identifies pressure ulcer risk before the
      operation. A literature review was first performed to elicit all the published
      HAPU risk factors before conducting a retrospective case-control study using
      medical records. The known HAPU risks were compared between patients with HAPU
      and without HAPU who underwent operations during the same period (July 2015
      December 2016). A total of 80 HAPU cases and 189 controls were analysed.
      Multivariate logistic regression analyses identified eight significant risk
      factors: age >= 75 years, female gender, American Society of Anaesthesiologists
      >= 3, body mass index < 23, preoperative Braden score <= 14, anaemia, respiratory
      disease, and hypertension. The model had bootstrap-corrected c-statistic 0.78
      indicating good discrimination. A cut-off score of >=6 is strongly predictive,
      with a positive predictive value of 73.2% (confidence interval [CI]: 59.7%-84.2%)
      and a negative predictive value of 80.7% (CI: 74.3%-86.1%). SPURS contributes to
      the preoperative identification of pressure ulcer risk that could help nurses
      implement preventive measures earlier.

PMID- 30289626
TI  - Barriers to mental healthcare and treatment for people living with HIV in the
      Asia-Pacific.

PMID- 30289628
TI  - Corrigendum.

PMID- 30289627
TI  - Rapid therapeutic advances in CFTR modulator science.
AB  - Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by variants
      in the gene encoding the cystic fibrosis transmembrane conduction regulator
      (CFTR) protein. Loss of CFTR function disrupts chloride, bicarbonate and
      regulation of sodium transport, producing a cascade of mucus obstruction,
      inflammation, pulmonary infection, and ultimately damage in numerous organs.
      Established CF therapies treat the downstream consequences of CFTR dysfunction
      and have led to steady improvements in patient survival. A class of drugs termed
      CFTR modulators has recently entered the CF therapeutic landscape. These drugs
      differ fundamentally from prior therapies in that they aim to improve the
      function of disease-causing CFTR variants. This review summarizes the science
      behind CFTR modulators, including their targets, mechanism of action, clinical
      benefit, and future directions in the field. CFTR modulators have dramatically
      changed how CF is treated, validated CFTR as a therapeutic target, and opened the
      door to truly personalized therapies and treatment regimens.

PMID- 30289625
TI  - Variance of IQ is partially dependent on deletion type among 1,427 22q11.2
      deletion syndrome subjects.
AB  - The 22q11.2 deletion syndrome is caused by non-allelic homologous recombination
      events during meiosis between low copy repeats (LCR22) termed A, B, C, and D.
      Most patients have a typical LCR22A-D (AD) deletion of 3 million base pairs (Mb).
      In this report, we evaluated IQ scores in 1,478 subjects with 22q11.2DS. The mean
      of full scale IQ, verbal IQ, and performance IQ scores in our cohort were 72.41
      (standard deviation-SD of 13.72), 75.91(SD of 14.46), and 73.01(SD of 13.71),
      respectively. To investigate whether IQ scores are associated with deletion size,
      we examined individuals with the 3 Mb, AD (n = 1,353) and nested 1.5 Mb, AB (n =
      74) deletions, since they comprised the largest subgroups. We found that full
      scale IQ was decreased by 6.25 points (p = .002), verbal IQ was decreased by 8.17
      points (p = .0002) and performance IQ was decreased by 4.03 points (p = .028) in
      subjects with the AD versus AB deletion. Thus, individuals with the smaller, 1.5
      Mb AB deletion have modestly higher IQ scores than those with the larger, 3 Mb AD
      deletion. Overall, the deletion of genes in the AB region largely explains the
      observed low IQ in the 22q11.2DS population. However, our results also indicate
      that haploinsufficiency of genes in the LCR22B-D region (BD) exert an additional
      negative impact on IQ. Furthermore, we did not find evidence of a confounding
      effect of severe congenital heart disease on IQ scores in our cohort.

PMID- 30289630
TI  - Tobacco Smoking and Psychotic-Like Experiences in a General Population Sample.
AB  - OBJECTIVE: Recent findings suggest an association between tobacco and psychosis,
      but whether this association is mediated by confounding factors is unknown.
      Psychosis-like experiences (PLEs) are a subclinical expression of psychosis. To
      disentangle the association of tobacco with PLEs, we examined data from a large
      US population-based, nationally representative sample. METHODS: Analysis was
      conducted on Wave 2 of the National Epidemiologic Survey of Alcohol and Related
      Conditions (N = 34,653 adults, conducted from 2004 to 2005). Participants were
      assessed with the Alcohol Use Disorder and Associated Disabilities Interview
      Schedule-IV. Twenty-two PLEs previously described as observed indicators of
      psychosis were used. Participants were stratified according to their smoking
      status (never/former/current) for 5 different types of tobacco. RESULTS: There
      was a significant association (ie, with 95% CIs for which the lower value was >=
      1) between smoking status and 14 of the 22 assessed PLEs. These associations
      remained significant after adjustment for sociodemographic variables (including
      urbanicity or ethnicity), lifetime drug use disorder, and past-year cannabis use.
      While 26.33% of nonsmokers reported at least 1 PLE, this prevalence was slightly
      higher in former smokers (27.48%) and rose as high as 39.09% in current smokers
      (for current smokers vs lifetime abstainers, adjusted OR = 1.33; 95% CI, 1.23
      1.45). All 22 PLEs had higher prevalence in smokers than in former smokers or
      lifetime abstainers. A total of 8.56% of smokers reported at least 5 PLEs,
      compared to 3.42% in lifetime abstainers (aOR = 1.56; 95% CI, 1.32-1.84).
      CONCLUSIONS: In a large population-based, nationally representative sample,
      smoking status was associated with various PLEs. This association was not
      explained only by other known risk factors of PLEs or schizophrenia. There is a
      need to identify the potential neurobiological mechanisms by which smoking and
      PLEs are associated, for patients and from a public health perspective.

PMID- 30289629
TI  - Suicide Methods and Specific Types of Accidental Death and Fatal Poisoning Among
      Discharged Psychiatric Patients: A National Cohort Study.
AB  - OBJECTIVE: Persons discharged from inpatient psychiatric units are at greatly
      elevated risk of dying unnaturally. We conducted a comprehensive examination of
      specific causes of unnatural death post-discharge in a national register-based
      cohort. METHOD: A cohort of 1,683,645 Danish residents born 1967-1996 was
      followed from their 15th birthday until death, emigration, or December 31, 2011,
      whichever came first. Survival analysis techniques were used to estimate
      incidence rate ratios (IRRs) comparing risk for persons with and without
      psychiatric admission history in relation to (a) suicide method, (b) accidental
      death type, (c) fatal poisoning type, and (d) homicide. RESULTS: More than half
      (52.5%, n = 711) of all unnatural deaths post-discharge were fatal poisonings,
      compared with less than a fifth (17.0%, n = 1,012) among persons in the general
      population not admitted. Just 6.8% (n = 92) of all unnatural deaths post
      discharge were due to transport accidents-the most common unnatural death type in
      the general population (53.4%, n = 3,184). Suicide risk was 32 times higher among
      discharged patients (IRR 32.3; 95% CI, 29.2-35.8) and was even higher during the
      first year post-discharge (IRR 70.4; 95% CI, 59.7-83.0). Among the suicide
      methods examined, relative risk values were significantly larger for intentional
      self-poisoning (IRR 40.8; 95% CI, 33.9-49.1) than for "violent" suicide methods
      (IRR 29.4; 95% CI, 26.1-33.2). The greatest relative risk observed was for fatal
      poisoning (irrespective of intent) by psychotropic medication (IRR 93.7; 95% CI,
      62.5-140.5). The highest post-discharge mortality rate was for accidental self
      poisoning among persons diagnosed with a psychoactive substance abuse disorder:
      290.1 per 100,000 person-years. CONCLUSIONS: Closer liaison between inpatient
      services and community care, more effective early treatment for comorbid
      substance abuse, enhanced psychosocial assessment following self-harm, and
      tighter medication surveillance could decrease risk of unnatural death post
      discharge.

PMID- 30289631
TI  - Safety of Pregabalin in Pregnancy.
AB  - In different parts of the world, pregabalin is an approved treatment for
      neuropathic pain syndromes, fibromyalgia, partial-onset seizures, and generalized
      anxiety disorder. Few studies have examined the safety of pregabalin exposure
      during pregnancy. Among 4 studies identified through a PubMed search conducted in
      September 2018, one small study (exposed n = 30) recorded a major malformation
      rate of 3.3%, which was similar to that in unexposed controls. Another small
      study (exposed n = 30) recorded increased rates of spontaneous abortion (23.3%),
      preterm birth (25.0%), and major malformations (7.7%), none of which reached
      statistical significance even in unadjusted analyses. A third study (exposed n =
      116) identified a significantly increased rate of major malformations (6.0%) but
      no increase in the rates of other adverse birth outcomes. The fourth and largest
      study (exposed n = 477 and n = 174; 2 datasets), which also presented the best
      statistical analysis, found no increase in the major malformation risk associated
      with pregabalin exposure. A subjective conclusion is that there is no clear
      signal that pregabalin exposure during pregnancy is associated with adverse
      gestational outcomes; however, this conclusion is limited by the consideration
      that all analyses were underpowered. Pregabalin use in pregnancy is therefore
      best restricted to circumstances in which the risk-benefit ratio is clearly
      favorable, and then, only after shared decision-making.

PMID- 30289632
TI  - What If I Need to Dispense or Prescribe an Opiate to a Patient?

PMID- 30289633
TI  - Dancing with the Zombies How a Dentist Ended the Zombie Apocalypse But Started
      Armageddon.

PMID- 30289634
TI  - Incommensurability in Endodontics The Role of the Endodontic Triad.

PMID- 30289635
TI  - Fabrication of a Denture without Try-In Clinical Trouble Shooting.
AB  - An immediate denture is a prosthesis which is fabricated without a denture try-in
      procedure in the patient's mouth and inserted at the same visit immediately after
      extraction of the teeth. This article presents an atypical case where the
      immediate interim denture had to be fabricated while the patient waited in the
      chair.

PMID- 30289636
TI  - Remember Pearl Harbor.

PMID- 30289637
TI  - What If I'm Asked to Refund a Payment Sent by an Insurance Carrier?

PMID- 30289638
TI  - Root Canal Treatment and Treatment After Endodontic Failure.

PMID- 30289639
TI  - The Case of the Missing Penny.

PMID- 30289640
TI  - We All Get Older (Hopefully!) Is It Our Age, Our Genes, or Something Else? Do
      Telomeres "Tell It All"?.
AB  - As healthcare professionals, we deal daily with "aging"'factors relating to our
      patients' dental treatment planning (and to ourselves). We are all are
      expressions of our DNA-the long molecules in our cells' nuclei that contain our
      genes which determine how proteins will be made to express who we are. Although
      genetics can be a confusing subject to understand, when trying to understand DNA,
      perhaps consider that you Do Not Abandon learning some of the basics of genetics.
      In today's evolving world of medical science, there is a major focus on genetics
      and genomics; analyzing one's genetic makeup to help in diagnosing and managing
      disease, and prescribing of medications (pharmacogenetics/pharmacogenomics). One
      aspect of interest is what we call "aging" or getting older, an expression of
      cellular "senescence"-most of our cells are programmed to commit suicide
      (apoptosis) over time. So we get wrinkles, our stomach sags and our hair goes
      gray. As described below, a normal physiologic process takes place at the end of
      your chromosomes to protect them. Over many years, this process can no longer
      protect your chromosomes and the cells die. However, if normal processes are not
      functioning correctly, the chromosomes continue to reproduce-if this is a cancer
      cell, the lack of cell suicide allows tumors to grow.

PMID- 30289641
TI  - Template Fabrication for Tomographical Diagnosis in Implant Dentistry: Two
      Clinical Cases.

PMID- 30289642
TI  - [Atherogenesis in human - clinical aspects of circulating immune complexes].
AB  - It has been suggested that circulating immune complexes containing low density
      lipoproteins (LDL-CIC) play a role in atherogenesis and are involved in the
      formation of early atherosclerotic lesions. The complexes, as well as anti-LDL
      antibody were found in the blood of patients with atherosclerotic process in
      various cardiovascular diseases, well as in the blood of animals with
      experimentally modulated atherosclerosis. One can assume that the presence anti
      LDL antibodies in blood is a result of an immune response that is induced by
      modification of lipoproteins. LDL-CIC differ from native LDL in many aspects.
      They have much lower levels of sialic acid, a smaller diameter and a higher
      density electronegativity than native LDL. The fraction of the LDL-CIC in serum
      is an important manifestation of the atherosclerotic process. LDL-CIC, unlike the
      native LDL is able to induce intracellular accumulation of neutral lipids,
      especially esterified cholesterol in cell cultures obtained from healthy human
      aortic intima and macrophages in culture. After removal of the LDL-CIC, the serum
      of CHD-patients loses its atherogenic properties. The titer of the LDL-CIC in the
      blood serum significantly correlate with the progression of atherosclerosis and
      in vivo has the highest diagnostic yield of measured among other lipid
      parameters. Increasing CIC- cholesterol could also increase the risk of coronary
      artery atherosclerosis.

PMID- 30289643
TI  - [Obesity: the modern view of a problem].
AB  - The article is a review of recent epidemiological observations concerning the
      prevalence of overweight and obesity in different countries among people of
      different gender, age. social and ethnic groups. It also presents and analyses
      health risks and comorbidities leading to disability and death as reported by
      domestic and foreign researchers. It was found that obesity has multifactorial
      pathogenesis directly related to energy balance, consumed and expended calories.
      The need of a multidisciplinary approach to the treatment and prevention of the
      disease is emphasized taking into consideration the influence of the environment
      and increasing urbanization on the development of the pathology as well as the
      role of government efforts to stimulate physical activity of the population in
      the framework of integral interdisciplinary programs and control over the quality
      of food. The priority areas for the correction of overweight include optimization
      of motor activity and diet correction.

PMID- 30289645
TI  - [The strategy for the surgical treatment of femoral fractures in polytrauma].
AB  - The review describes peculiarities of the choice of time and methods of
      osteosynthesis offemur fractures of different localization in patients with
      multiple injuries in accordance with modern concepts of treatment of severe
      multiple and associated lesions. Analysis of domestic and foreign literature
      shows that earlyfixation of the femur in case of polytrauma can reduce the
      mortality rate associated with complications and improve the functional outcome.
      Terms of osteosynthesis of the femur in polytrauma should be chosen taking into
      account the severity of the injury, the patient's condition, and the period of
      traumatic disease. The procedure of osteosynthesis must not be a threat to the
      clinical condition. The choice of the method for fixation of the femur depends of
      fracture type and location, the presence of fractures in the adjacent and remote
      segments. The minimally invasive techniques of osteosynthesis of the femur and
      staged surgical treatment of the victims in an unstable state should be chosen
      for the treatment of multiple injury in accordance with the concept of "Damage
      Control Orthopedics".

PMID- 30289644
TI  - [The use of reamberin in combined intensive care of acute poisoning].
AB  - This review is focused on the substrate antihypoxant reamberin used in intensive
      therapy of acute poisoning with special reference to the mechanisms of its action
      consisting in the reduction of the severity of metabolic disorders manifested as
      a decrease of tissue hypoxia, recovery of antioxidant defense and suppression of
      the activity of lipid peroxidation and endotoxicosis. The antihyhypoxant activity
      of reamberin is apparent as the reduction of the hypoxic brain lesions in
      patients with acute poisoning which leads to a significant improvement in the
      clinical course of acute poisoning and decreases the number of adverse outcomes.

PMID- 30289646
TI  - [ABO and RHD blood types distribution of the patients treated in the Federal
      Center of Cardiovascular Surgery of Krasnoyarsk].
AB  - The knowledge of blood types frequency in hospital patients helps to plan and
      perform transfusion therapy at blood donor centers. The distribution of patients'
      blood by ABO groups and RhD allows to more efficiently organize and use donor
      blood banks. The risk of a disease is related to genome composition and is
      inherited with an ABO blood type. Every person should know his (her) ABO blood
      type and RhD to enable early identification of the first symptoms of an illness.
      Materials and methods. This work is based on the study of 4831 blood samples from
      patients treated at the Center of Cardiovascular Surgery in 2013 (2885 (59,7%)
      men of the mean age 55 years and 1946 (40,3 %) women of the mean age 57 years).
      Results. Type A blood occurred most frequently (1787 or 37,0% samples) followed
      by group O (1625 or 33,6% samples). Samples of group B made up 1025 of the total
      (21,2%), AB blood group was found in 394 samples (8,2%). Conclusion. The blood
      types distribution of the ABO system in the patients treated at the Center of
      Cardiovascular Surgery was characterized by the following pattern: A > O > B >
      AB. Group A was identified in 37,0% of the patients. Its frequency is similar to
      that in the population of the western part of Russia and Moscow but different
      from that in the people living in nearby regions. The frequency of RhD system
      antigens is comparable in all regions of Russia. CcDEe, ccDEe, CcDee, CCDee are
      considered to be the most widespread phenotypes. The residents of the Krasnoyarsk
      region and some nearby regions having blood type A apply to the Center of
      Cardiovascular Surgery with cardiovascular disorders more frequently than those
      with others ABO blood types.

PMID- 30289647
TI  - [The prognostic value of transient arterial hypertension in patients with chronic
      heart insufficiency and preserved left ventricular ejection function].
AB  - : There is a J-like dependence of mortality among patients with chronic heart
      insufficiency (CHI) on arterial pressure (AP). This implies the possibility of
      not only elevation but also fall of AP in such patients. The aim of the study was
      to determine the frequency and prognostic value of arterial hypotension episodes
      in CHI patients with preserved left ventricular ejection function (CHI-PEF). .
      Materials and methods: The study included 169patients (74 men and 95 women) with
      CHI (mean age 56,3+/-10,9 yr). All of them had PEF higher than 50%. 105 patients
      had FCII CHI, 64 ones FCIII CHI. Stage IIA was documented in 136 and stage IIB in
      33 patients. Duration of the study 24 months. The combined end point included non
      fatal myocardial infarction and cardiovascular death. Results: Arterial
      hypotension at office AP was diagnosed in 16 (9,5%) patients, transient arterial
      hypotension based at 24 hr AP monitoring in 104 (61,6%) patients. A total of 8
      combined end points were documented during the study period. All these patients
      had transient systole-diastolic and/or systolic arterial hypotension . No
      myocardial infarction or lethal outcome developed in CHI patients without
      episodes of arterial hypotension (x=4,28, r=0,04). Conclusion: 24 hr AP
      monitoring in CHI-PEF patients permits to significantly increase the frequency of
      detection ofpotentially dangerous changes of AP. Transient arterial pressure
      occurs in 61.6% of the FCII-III CHI-PEF patients. Transient systole-diastolic
      arterial hypotension significantly increases the risk of non-fatal myocardial
      infarction and cardiovascular death in CHI-PEF patients

PMID- 30289648
TI  - [Diurnal rhythm of arterial pressure in patients with acromegaly].
AB  - 24 hr monitoring of arterial pressure (AP) in 46 patients with acromegaly in
      active phase revealed systolic-diastolic arterial hypertension. Analysis of
      diurnal profile showed the absence of the normal nocturnal fall in AP (non-dipper
      profile) and the significant rise in the number of patients with elevated
      nocturnal AP (night-peakers).

PMID- 30289649
TI  - [Pulmonary function in patients with type 2 diabetes and coronary artery
      disease].
AB  - : Currently, there is no convincing evidence of respiratory failure in patients
      with diabetes mellitus (DM) and coronary artery disease (CAD). Aim: To evaluate
      the differences in the main parameters of pulmonary function in patients with
      isolated type 2 diabetes and diabetic patients with CAD. Materials and methods:
      Patients with diabetes were allocated to two groups depending to the presence of
      CAD. The assessment of carbohydrate and lipid metabolism, as well as the
      measurement of inflammatory markers were performed using standard methods of
      clinical and biochemical analysis. Respiratory function and diffusion capacity of
      the lungs (DLCO) were assessed using a body plethysmograph Elite Dl-220v.
      Results: Main pulmonary functional test parameters were within normal values,
      except residual volume in diabetic patients. Patients with concomitant CAD
      demonstrated lower values of the studied parameters compared to non-diabetic
      ones. A number of volume and flow rate parameters as well as DLCO correlated with
      systemic inflammation, decompensation of carbohydrate and lipid metabolism, and
      duration of diabetes. Conclusion: Diabetic patients with CAD suffered from
      respiratory failure, manifested as decline in pulmonary function and DLCO. Blood
      glucose levels, inflammation symptoms, dyslipidemia and myocardial dysfunction
      are among suspected causes contributing to the development and acceleration of
      this decline.

PMID- 30289650
TI  - [Respiratory sleep disorders in vehicle drivers].
AB  - Aim: To determine the frequency of respiratory sleep disorders (RSD) in vehicle
      drivers, peculiarities of their clinical status and workability. Material and
      methods: The study included the main group of 106 vehicle drivers (VD) and
      control group of 104 of subjects of other professions. The following methods were
      used: fibrooptic endoscopy, standard questionnaire, pulsoxymetry, 24 hour blood
      pressure and ECG monitoring, psychophysiological testing of 86 VD with RSD,
      arterial hypertension with and without complications. Results: The clinical and
      instrumental signs of RSD were found in 65.1% VD of the main group and 47,1% of
      controls. Transitory ischemic attacks, cardiac arrhythmias and their combination
      occurred more frequently in VD (82.6, 59.2, and 52.2% respectively) than in
      controls (51.0, 44.8, and 32.6%). In most observations of VD, the smoking rate
      (98.1%), alcohol intake (95.3%), increased body mass (74.5%), obese (21,7%)
      dyslypoproteidemia (73.6%), left ventricular hypertrophy (54.7%) and arterial
      hypertension (57.5%) were significantly higher than in controls : S (76.9%), AI
      (75.0%), IBM (56.7%), O (18.3%), DLP (59.6%), LVH (41.3%), AH (39.4%). Chronic
      obstructive pulmonary diseases was diagnosed in 55.6% of VD and 51.9% of
      controls, diabetes mellitus in 34.9% and 20.2%, epidemiological forms of ischemic
      heart disease in 22.6% VD and 20.2% controls. Psychophysilogical testing of VD
      group revealed deterioration of professional qualities and functions of the
      drivers with respiratory sleep disorders. Conclusion: Significant frequency of
      RSD among VD (65.1%) in comparison with subjects of other professions (47.1%) was
      documented. RSD cause deterioration ofprofessional abilities of VD which
      increases the risk of traffic accidents.

PMID- 30289651
TI  - [HLA-DR expression on monocytes as a prognostic criterion for the development of
      pyoinflammatory processes at various stages of surgical treatment].
AB  - We studied relative content of CD14+HLA-DR in 214 patients including those with
      aseptic instability and stable implants of the knee and the hip, periprosthetic
      infection of the hip, chronic posttraumatic osteomyelitis of long tubular bones,
      and osteomyelitis generalization (sepsis). We determined HLA-DR expression on
      monocytes by laser flow cytofluorometry using Beckman Coulter Epics XL (USA)
      cytometer and monoclonal antibodies (Immunotech Company, France). It has been
      demonstrated, that the decrease in HLA-DR expression on monocytes can be one of
      the mechanisms of increasing immune disorders in patients with orthopedic
      pathology and monitoring HLA-DR monocytic expression can be used as a prognostic
      criterion of developing pyoinflammatory processes at the stages of surgical
      treatment.

PMID- 30289652
TI  - [New anticoagulants in clinical practice. Effectiveness and problems].
AB  - We analyze the effectiveness of new oral anticoagulants and antivitamins K for
      the treatment of patients with venous problems, atrial fibrillation, and acute
      coronary syndrome with reference to advantages of this therapy and methods of
      prevention of complications of these conditions.

PMID- 30289653
TI  - [Hepatic tuberculosis with the development of fibrosis and concomitant
      steatohepatitis].
AB  - Tuberculous lesions of the liver frequently occur in autopsy material, even
      though most of them are clinically unapparent. Pathogenetically, hepatic
      tuberculosis is a manifestation of general military tuberculosis with the
      infection brought in through the hematogenous route (through the hepatic artery
      or the portal system) as a result of intestinal or mesenteric lymph node
      tuberculosis. We report a case of combination of hepatic tuberculosis and
      diabetes mellitus in a young woman with reference to the clinical course of the
      disease, its diagnostics and treatment.

PMID- 30289654
TI  - [Clinical manifestations of antiphospholipid syndrome associated with lesions of
      the central nervous system].
AB  - Antiphospholipid syndrome (APS) is one of the important but poorly known
      conditions. Its symptoms are ofparticular interest for neurologists since thrombi
      are most often localized in the cerebral blood vessels which leads to ischemic
      cerebrovascular accidents (AICS). APS can also manifest itself in the following
      symptoms: epileptic attacks, dementia, headache, chorea, peripheral neuropathy,
      myelo- and encephalopathy phenomenologically similar to multiple sclerosis. This
      article presents a clinical case of secondary APS with the neurological
      manifestations in a 25-year-old female patient.

PMID- 30289655
TI  - [Remote preconditioning phenomenon. prospects for use in pathology of lung and
      gastrointestinal tract].
AB  - The literature data on the effectiveness of remote ischemic preconditioning (RIP)
      in the prevention of lung injury are contradictory. Authors of some works argue
      that RIP prevents lung damage during surgical interventions, the authors of other
      publications claim that the RIP does not protect lung against pathological
      processes. It is obvious that there is an urgent need for multicenter, randomized
      trials aimed at studying RIP protective effects against pathological processes in
      lung. Also required is clinical evaluation of the effectiveness of RIP in the
      thromboembolism of pulmonary arteries, the transplantation of the lungs and
      intestinal infarction. Remote preconditioning prevents the intestine injury
      associated with abdominal aortic aneurysm repair. Experimental data indicate that
      RIP has the hepatoprotective effect during ischemia and reperfusion injury of
      liver, septic or haemorrhagic shock. The question of whether the DIP has a
      protective effect during ischemia-reperfusion of the pancreas remains open.

PMID- 30289656
TI  - [Disorders of carbohydrate metabolism in chronic obstructive pulmonary disease].
AB  - The literature data and our own experience suggest that chronic obstructive
      pulmonary disease can be an important risk factor of type 2 diabetes mellitus.
      The relationship between these two condition is virtually unexplored and
      pathogenteic mechanisms behind it remain unclear. There are reasons to attribute
      an important role to insulin resistance as one of the leading mechanisms. It is
      in the focus of the present work.

PMID- 30289657
TI  - [Iron deficiency syndromes associated with diseases of the gastrointestinal
      tract: state-of-the-art and new prospects for treatment].
AB  - Organs of the gastrointestinal tract (GIT) are essential for iron metabolism and
      hematopoiesis regulation. Iron deficiency is accompanied by a large number of
      diseases of GIT. The article discusses the problem of diagnosis and treatment of
      anemia, It describes mechanisms of development of anemia associated with
      bleeding, malabsorption, and chronic inflammation. It provides current data on
      the use of oral and intravenous iron-containing drugs, discusses advantages of
      the new oral form of sucrosomial iron for the treatment of anemia associated with
      GIT diseases.

PMID- 30289658
TI  - [The possibilities and limits of modern bronchodilating therapy for COPD].
AB  - This article is a critical review designed to assess the efficacy and safety of
      modern bronchodilating therapy for COPD patients.

PMID- 30289659
TI  - [Alterations of physiological rhythms in neurodegenerative disorders: problems
      and prospects of light therapy].
AB  - This review provides an outline of circadian disorders associated with
      neurodegenerative diseases of the brain in the elderly, including Alzheimer's
      (AD) and Parkinson's diseases (PD). Since light is one of the most powerful
      environmental cues synchronizing physiological rhythms, exposure to bright light
      is often used to treat sleep disorders, behavior of patients with severe
      dementia, gait, and other functions disordered in CNS pathologies.
      Photobiomodulation effects of the low-energy laser and LED radiation is also
      considered as a potential tool for the rehabilitation of patients with various
      pathologies. It yielded positive results in the treatment of both PD and AD. An
      external factor that can exacerbate a course of neurodegenerative diseases is
      light pollution. Irrational artificial lighting can cause jet lag, affect visual
      and cognitive functions. The review also summarizes the current understanding of
      fractal dynamics of physiological rhythms in healthy subjects (including brain
      activity) and their reduced complexity in pathological conditions. The loss of
      multiscale complexity of brain electrical activity has been documented for
      patients with AD, PD, epilepsy, and schizophrenia. It is thought to reflect
      fundamental changes in the regulation of the body's circadian rhythms. Recently,
      M.V Zueva proposed and theoretically substantiated the hypothesis that allows
      taking another look at the prospects for the use of light stimulation. It is
      expected that the use of stimuli with fractal structure can help to restore the
      retina and brain's functions in neurodegenerative diseases by reactivation of
      neuronal plasticity and be an innovative method for the treatment of
      neurodegenerative disorders.

PMID- 30289660
TI  - [Arterial hypertension as a risk factor of intra-atrial thrombosis in patients
      with atrial fibrillation of non-valvular etiology].
AB  - : The article considers the influence of arterial hypertension on the frequency
      of intra-atrial thrombosis in patients with atrial fibrillation (AF) of non
      valvular etiology. Materials and methods: 38 patients were examined (26 men and
      12 women) aged 35 to 75 years with documented AF. Paroxysmal AF was diagnosed in
      10 patients (26.32%). The persistent and permanent forms of arrhythmia were
      revealed in 14 cases (36.84%). Stage II-III hypertensive disease (HD) was
      diagnosed in 27 patients (71.1%). The transthoracic and transesophageal
      echocardiography was performed with the use of ultrasonic devices such as Aloka
      SSD-4000 ProSound (Japan) and PhilipsIE 33 (USA). Results: The analysis of
      results of echocardiography (both transthoracic and transesophageal) made it
      possible to detect intra-atrial clots in 54,8% of the patients with AF of non
      valvular etiology. Atrial cavity thrombosis was registered in 15 of the 22 cases
      (68,2%) among the patients with hypertension as a direct cause of AF or another
      concomitant pathology. Lower blood flow velocity from the left atrial appendage
      was registered in hypertensive patients compared to those without hypertension -
      29.0 (4.2) and 35.4 respectively (8.1) mm/s (p = 0.038; Student's t-test). The
      reduction of the peak bloodflow velocity in the left atrial appendage was
      proportional to the increase of hypertension (R = -0,861; p <0,001; R -
      Spearman's coefficient). The frequency of intra-atrial thrombosis did not depend
      on the form of atrialfibrillation and duration of the arrhythmic anamnesis.
      Conclusion: Hypertension is an independent predictor of thromboembolic
      complications in atrial fibrillation of non-valvular etiology.

PMID- 30289661
TI  - [The clinical significance of insulin resistance, impaired carbohydrate and lipid
      metabolism in the development of microcirculation pathology in patients with
      chronic heart failure and type 2 diabetes mellitus].
AB  - Patients with chronic heart failure and diabetes mellitus type 2 experience
      continuous progression of organ damage as a result of hemodynamic and metabolic
      disorders. An important role in pathogenesis of organ damage belongs to
      pathological types of microcirculation, endothelial dysfunction and insulin
      resistance. But the role of insulin resistance and its contribution to the
      formation of endothelial dysfunction and peculiarities of microcirculation in
      patients with chronic heart failure and type 2 diabetes mellitus is unknown. This
      study shows significant association between insulin resistance, disorders of
      carbohydrate and lipid metabolism, development of microcirculatory disturbances
      and endothelial dysfunction.

PMID- 30289662
TI  - [Differential diagnostics of febrile conditions in an emergency care clinic].
AB  - We undertook the analysis of 157 cases of fever at the stages of polyclinic -
      admission department - hospital treatment for the purpose of elucidating the
      structure of febrile syndrome. Pneumonia developed in 45 patients, infectious
      endocarditis in 34, chronic alcoholic hepatitis in 21, rheumatoid arthritis
      (pseudoseptic variant) in 2, systemic lupus erythematosus in 1, polymyositis in
      2, acute pyelonephritis (exacerbation of chronic pyelonephritis) in 15, tumours
      of different localization in 37 patients. We evaluated the informative value of
      some acute-phase blood characteristics obtained, results of X-ray and ultrasonic
      studies for early diagnostics of pneumonia and infectious endocarditis.

PMID- 30289663
TI  - [Peculiarities of the psychic state and quality of life in patients with duodenal
      ulcer in the context of chronomedicine].
AB  - Most clinicians consider duodenum ulcer as a psychosomatic disease. Objective: To
      show the interdependence of this condition and mental disorders and their
      relation to disturbances of melatonin production . Materials and Methods: 15
      patients with seasonal DU and 15 healthy subjects of the control group were
      examined during 3 years using laboratory, endoscopic, and standard
      psychodiagnostic methods. Results. It was found that all patients with
      exacerbation of DU experienced enhanced anxiety, reduced background mood, and
      impaired quality of life based on general health and mental health scoring
      scales. The circadian rhythm of melatonin production was markedly distorted
      throughout the observation period but especially during exacerbations of the
      disease. Conclusions. The results indicate a high degree of correlation between
      DU and mental disorders caused by impaired production of melatonin. It suggests
      common etiological mechanisms of DU and psychosomatic symptom complex.

PMID- 30289664
TI  - [Biliary reflux-gastritis: etiology, pathogenesis and modern principles of
      treatment].
AB  - Objective. To study etiopathogenetic aspects of biliary reflux-gastritis (RG) and
      develop modern principles of its therapy depending on acidity of stomach
      contents, atrophy ofgastric mucosa, and Helicobacter pylori infection. Different
      pathogenetic mechanisms of RG are discussed with special reference to bile flow
      into the antrum as a result of duodenogastric reflux. It is shown that the use of
      de-nol and probiotic ProBiotic Complex for the treatment of biliary reflux
      gastritis increases effectiveness of H. pylori eradicationby 18.2% and prevents
      the development of bowel dysbiosis.

PMID- 30289665
TI  - [Results of application of a new method for the treatment of hallux valgus of the
      first toe].
AB  - Background: The aim of the present article was to report our experience with the
      treatment of patients with hallux valgus and to perform comparative analysis of
      the results of the newly proposed and standard methods for its surgical
      correction. Methods: The data on 70patients (101 feet) with hallux valgus that
      were operated on between 2011 and 2015 in St. Petersburg Hospital No 2 using the
      new and standard methods were analysed. The functional assessment (AOFAS score)
      and X-ray examination were performed preoperatively, 3 and 12 months after the
      procedure. Comparative analysis between patients undergoing surgical correction
      by the new and standard methods has been undertaken. Results: We did not find any
      significant difference between the two groups in mean AOFAS score 12 months after
      surgery. Nevertheless, the function score of the patients treated by the newly
      proposed method (79.4+/-6.5 in 3 months) was significantly better than in those
      given the standard treatment (72.2+/-7.6 in 3 months). Mean intermetatarsal angle
      12 months after surgery by standard and new methods was 9,7+/-0,7 degrees  and
      8,6+/-0,7 degrees  (p<0.05), mean metatarsophalangeal angle 13,6+/-0,9 degrees 
      and 13,0+/-1,1 degrees  (p<0,05) respectively. Conclusion: According to the data
      obtained, the original method of hallux valgus surgical correction allows to
      improve its functional and x-ray results.

PMID- 30289666
TI  - [Myocardial infarction at the border of two centuries: demographic and social
      tendencies].
AB  - The aim of the study was to compare the incidence, onset, and the course of acute
      myocardial infarction (AMI) among the population of Tomsk in 1984 and 2013.
      Materials and Methods: The study was based on the analytic database of the World
      Health Organization epidemiology program AMI Registry (RAMI). Epidemiology of AMI
      was studied among the urban population aged 20 years and older. A total of 739
      and 983 AMI cases were analyzed in 1984 and 2013 respectively. Results: The
      proportion ofpatients older than 60 years significantly increased in the age
      structure of AMI patients during the study period. The occurrence of AMI with
      atypical clinical onset increased by three times; anamnestic background of AMI
      worsened; and the number of episodes with preinfarction angina increased.
      Analysis of the AMIpicture revealed an increase in the occurrence of Q (QS)-wave
      myocardial infarction and a significant rise in the frequency of complications;
      the frequency of chronic heart failure, cardiac arrhythmias, and recurrent AMI
      was especially high. Conclusion: An increase in the proportion of elderly and
      senile people in the age structure resulted in an aggravation of the diagnostic
      and prognostic features of AMI during the study period. Evidently, the existing
      situation requires optimization of medical assistance for patients of older age
      groups with emphasis on the development and the implementation of recommendations
      concerning the prediction, diagnosis, treatment, and rehabilitation of these
      patients.

PMID- 30289667
TI  - [A rare case of oxalate nephropathy with acute renal injury].
AB  - Objective: This case demonstrates the difficulty of diagnostics of oxalate
      nephropathy and possibility of development of acute kidney injury. Summary: The
      paper describes a patient with oxalate nephropathy and acute kidney injury.
      Specific features of oxalate diathesis are discussed as well as approaches to its
      diagnosis. Clinical peculiarities and diagnostic difficulties are described.
      Conclusions: Early diagnosis of oxalate nephropathy and treatment permits to
      improve prognosis.

PMID- 30289668
TI  - [Case report of a combination of periodic disease and irritable bowel syndrome].
AB  - The article reports a case of atypical picture of a combination of periodic
      disease and irritable bowel syndrome in a 52 year old patient.

PMID- 30289669
TI  - [Clinical rhetoric in the high school].
AB  - Clinical rhetoric is a science concerned with consistent patterns of speech
      behavior in different situations of interaction with colleagues, patients, and
      specialists in various disciplines with a view to extending their practical
      applications for the enhancement of efficiency of meaningful contacts. The
      history of this science as a means of rational communication with patients and
      medical profession dates back to the times of Hippocrates. Its importance greatly
      increased under the present-day conditions of high-technology and therapeutically
      aggressive medicine. Clinical rhetoric is based on the principles of general
      rhetoric. A clinician must be prepared for he fruitful and constructive relations
      with a variety of partners including patients, healthy subjects, administrators,
      lawyers, businessmen, and colleagues. Four main peculiarities of clinical
      rhetoric are distinguished: any debate is possible only in the form of
      discussion, both the form and content of the opponent's arguments should be
      treated with respect, the speaker must himself draw attention to the weak points
      of his theses, all discussions must have the form of a "captain council" in which
      the shipboy is the first and the captain the last to speak. Traditional forms of
      clinical discussion include counselling, doctor's rounds, consilia, and
      demonstrations. Collective forms of stimulating creative thinking, such as
      brainstorming and foresight have especially good prospects. These approaches
      appear to be of special value for the solution of heuristic problems. Teaching
      clinical rhetoric should be initiated since term IV when students begin to
      understand the role of a doctor as a key figure in the organization of the
      diagnostic and therapeutic process. Further development of Hippocrates'
      traditions of collective communication may significantly promote the intellectual
      return from clinical and scientific discussions in medicine.

PMID- 30289670
TI  - [Scientific legacy of I.V. Davydovsky - philosophical foundations of general
      pathology].
AB  - The vast empirical material on pathogenesis of diseases has thus far been
      accumulated. However, its systematization and philosophical interpretation have
      not been given due attention since the time of I.V. Davydovsky. The value and
      topicality of I.V. Davydovsky' ideas need a fresh view andfurther development in
      the context of knowledges of the XXI century. The analysis of the selected
      provisions of I.V. Davydovsky offered in the article will hopefully contribute to
      their introduction into applied medicine.

PMID- 30289671
TI  - [Clinical significance of heart rhythm variability in patients with
      gastroesophageal reflux disease].
AB  - Cardiac manifestations of gastroesophageal reflux disease (GERD) including
      retrosternal pain and cardiac rhythm disorders were often mentioned in early
      publications. However, classification of GERD adopted at the 2005 Montreal
      congress does not include such conditions. Non-coronarogenic pain in the thoracic
      cage is recognized to be a typical esophageal syndrome while the reflex spasm of
      coronary arteries and cardiac rhythm disorders associated with GERD should be
      regarded as manifestations of comorbidity of GERD and cardiovascular diseases.
      Arrhythmias occur in 30% of patients with GERD, but relevant therapeutic and
      preventive modalities are poorly developed. Nor are there reliable predictors of
      arrhythmias. An important role in their pathogenesis in patients with GERD is
      played bydisbalance of sympathetic and parasympathetic components of vegetative
      nervous system (VNS). One of the approaches to studying this issue is the
      analysis of heart rhythm variability (HRV). We consider basic principles of
      clinical interpretation of the results of HRV research that allow to evaluate the
      state of VNS and interaction of its components. Analysis of recent publications
      gives evidence that many HRV parameters depend not only on the balance between
      components of VNS as was believed by earlier authors (for the lack of their
      reciprocal relationship) but also on the activity of these components. Other
      modulating factors include the heart rate, respiratory pattern, intrathoracic
      pressure, and diastolic atrial extension. We report the results of HRV assessment
      in patients with GERD that illustrate heart rhythm rigidity and predominant
      disorders of activity of the parasympathetic component of VNS especially well
      apparent in patients with erosive reflux esophagitis. However, other authors
      demonstrate oppositely directed changes and the involvement of the sympathetic
      component. A possible cause of this discrepancy is factors other than VNS
      influencing HRV. It is concluded that analysis of HRV can be used to develop a
      method for the prevention of GERD-associated arrhythmia. The diagnostic value of
      such method is limited and requires new algorithms for data interpretation taking
      account of their multifactorial origin.

PMID- 30289672
TI  - [Atheromatosis of arterial intima].
AB  - Phylogenetically late arterial intima of the elastic type contains no proteins
      for the transfer of ligandless oxidized low density lipoproteins (LDLP) for
      sedentary macrophages adsorbed on the matrix. Phylogenetically early cells
      realize the extracellular digestive reaction by releasing proteolytic enzymes
      (metalloproteinases) into intimal matrix that hydrolize matrix proteoglycans,
      adsorbed ligandless LDLP, detritus, and complete lysosomal hydrolysis of the most
      hydrophobic polyenic cholesterol esters (poly-ECS). Smooth muscle cells migrate
      from the middle muscular layer of the arterial wall, change their contractile
      phenotype to secretory one, and synthesize in situ de novomatrix proteoglycans.
      The arterial wall has three layers (monolayer endothelium, intimal media (smooth
      muscle cells), and adventitia) only in elastic type arteries. It is desirable to
      elucidate functional differences between phylogenetically early
      sedentarymacrophages and monocytes-macrophages of later origin and understand
      whether theydepends on specific features of activity of scavenger eceptors, CD36
      translocases, expression of acid hydrolases synthesis for poly-ECS or realization
      of the extracellular digestion reaction. We believe that formation of
      atheromatous masses takes place in the matrix of arterial intima rather than in
      lysosomes taking into account limited possibilities for monocytes-macrophages to
      realize endocytosis of ligandless LDLP from the matrix. Given that atheromatosis
      is a syndrome of deficit of essential polyenic fatty acids (PFA) in the cells,
      intimal atheromatosisshould be regarded only as partial utilization of excess PFA
      in the matrix of elastic type arteries. At later stages of phylogenesis, intima
      was formed from media smooth muscle cells.

PMID- 30289673
TI  - Welcome Changes for ASSE.
AB  - Look for the rebrand to start rolling out in the first quarter of 2018 with a
      refreshed website.

PMID- 30289674
TI  - On the Move.

PMID- 30289675
TI  - [The clinical course of atrial fibrillation in patients with coronary heart
      disease].
AB  - : The modern medical literature practically does not contain clinical
      publications reporting studies of factors responsible for progression of atrial
      fibrillation (AF) in patients with coronary heart disease (CHD). It accounts for
      the importance of investigations into evolution of the clinical course of AF in
      such patients. Aim: To elucidate evolution of the clinical course of AF in
      patients with CHD in a long-term prospective study. Materials and methods: The
      study included. 112 patient aged 57-74 (mean 67.44+/-3.3) years with CHD and
      paroxysmal form of AF carried outfrom 2011 to 2015. Evolution of the clinical
      course of AF was evaluated based on the number of arrhythmic attacks during the
      last 3 months. The appearance of prolonged persistent AF episodes or permanent AF
      was regarded as progression of arrhythmia. Results: During the 4 year study, 64
      (57,2%) patients (group 1) did not experiencea rise in the frequency and duration
      of AF attacks. Progression of arrhythmia was documented in 48 (42,8%) of the 112
      (100%) patients (group 2). These patients more frequently had the history of
      myocardial infarction and chronic heart failure than patients of group 1. The
      latter had the mean values of left ventricular (LV) ejection fraction 61,23+/
      6,24%, i.e. significantly higher than 48,47+/-8,4% in group 2.47 and 28 % of the
      patients in group 2and 1 respectively suffered mitral regurgitation (p<0,05).
      Patients of group 2 had significantly more akineticzones. Intake of nitroglycerin
      in group 1 resulted in positive dynamics of local LV contractility that did not
      change in patients of group 2. Conclusion: 42,8% of the patients with CHD and
      paroxysmal form of AF experienced progression of arrhythmia into a persistent or
      permanent form. Predictors of AF progression in patients with CHD are the history
      of myocardial infarction, chronic heart failure, mitral regurgitation, and
      irreversible changes in local myocardial LV contraction.

PMID- 30289676
TI  - [Polymorphisms of genesencoding enzymes of the xenobiotic detoxification system
      and the risk of infectious endocarditis].
AB  - Infectioue endocarditis (IE) is frequently associated with the use of narcotic
      drugs, glucocorticosteroids, and cytostatics that are metabolized in the body by
      enzymes of the xenobiotic detoxification system (XDS). This work was aimed at
      elucidating association between IE and mononucleotide polymorphisms of genes
      encoding XDS enzymes. 46 IE patients and 114 subjects without cardiovascular
      diseases (controls) underwent genotyping for polymorphic loci of cytochrome P450
      1A1 gene I462V (CYP1A1), I105VandA114V gene of glutathione-S-transferase Pi1
      (GSTP1) using allele-specific PCR. The study revealed association of CYP1A1
      I462VandGSTP1 I105V with IE while IE proved unrelated to GSTP1 A114V
      polymorphism. Combination of homozygous variant I462I of the CYP1A1 gene and
      heterozygous variant I105V/ of the GSTP1 gene was associated with the 9-fold
      increase of the risk of IE in the subjects practicing intravenous druginjections
      or having congenital and acquired heart failure or implanted valve prostheses.
      These findings suggest the necessity of further studies on the role of XDS in
      pathogenesis of IE and other infectious diseases.

PMID- 30289677
TI  - Help the 'Bulletproof' Employee Make the Connection.
AB  - Inspire conformance through influence, awareness, and definitively through the
      identification of the harmful and helpful biases we all have, some of them buried
      deep within us.

PMID- 30289679
TI  - [Tendencies in cardiovascular morbidity and mortality in the population of
      Siberia].
AB  - Aim: To characterize differences in the risk of development (RD) of myocardial
      infarction (MI) and stroke during 16 years in an open Siberian population aged 25
      64 years and suffering vital exhaustion (VE). Materials and methods: We examined
      a random representative sample of 657 men and 870 women from the Novosibirsk
      population in the framework of the WHO "MONICA-psychosocial" screening III
      program (1954). It included registration of socio-demographic data and cases of
      VE. A total of 15 episodes of MI and 35 strokes were documented in 30 women and
      22 men. Results: The level of VE in men was 66,8% (high in 14,6%), in women75,7%
      (high in 44,4%). RD of MI estimated from the relative risk (RR) in men with
      VE(RR=2) was higher than in women. It was higher in divorced women (RR=5,4) than
      in men (RR=4,7). RD of MI was higher in men with VE (OR=2,2 in subjects having
      elementary education, OR=3,7 in bachelors, OR = 7 in widowers;at the age from 45
      to 54 years OR=3,8, at the age from 55 to 64 years OR=5,9) than in women. The
      overall RD of stroke in subjects of either sex with VE was not significantly
      different (OR=3,34 in women and 3,1). However, it was higher than in women in men
      with VE having partially completed secondary-level and elementary education
      RR=4.8), in divorced and widowed men (RR=3.8 and 3.6 respectively. Conclusion:
      The study showed that the prevalence of VE in the population aged 25-64yearsis
      higher than in other age groups and higher in women than in men. VE is a more
      reliable predictor of MI in men than in women; it is a predictor of stroke in
      either sexes.

PMID- 30289680
TI  - Ultraviolet-Assisted Direct Ink Write to Additively Manufacture All-Aromatic
      Polyimides.
AB  - All-aromatic polyimides have degradation temperatures above 500  degrees C,
      excellent mechanical strength, and chemical resistance, and are thus ideal
      polymers for high-temperature applications. However, their all-aromatic structure
      impedes additive manufacturing (AM) because of the lack of melt processability
      and insolubility in organic solvents. Recently, our group demonstrated the design
      of UV-curable polyamic acids (PAA), the precursor of polyimides, to enable their
      processing using vat photopolymerization AM. This work leverages our previous
      synthetic strategy and combines it with the high solution viscosity of
      nonisolated PAA to yield suitable UV-curable inks for UV-assisted direct ink
      write (UV-DIW). UV-DIW enabled the design of complex three-dimensional structures
      comprising of thin features, such as truss structures. Dynamic mechanical
      analysis of printed and imidized specimens confirmed the thermomechanical
      properties typical of all-aromatic polyimides, showing a storage modulus above 1
      GPa up to 400  degrees C. Processing polyimide precursors via DIW presents
      opportunity for multimaterial printing of multifunctional components, such as
      three-dimensional integrated electronics.

PMID- 30289681
TI  - Fast and Scalable Hydrodynamic Synthesis of MnO2/Defect-Free Graphene
      Nanocomposites with High Rate Capability and Long Cycle Life.
AB  - The integration of metal oxides and carbon materials provides a great potential
      for enhancing the high energy and power densities of supercapacitors, but the
      rational design and scalable fabrication of such composite materials still remain
      a challenge. Herein, we report a fast, scalable, and one-pot hydrodynamic
      synthesis for preparing ion conductive and defect-free graphene from graphite and
      MnO2/graphene nanocomposites. The use of this hydrodynamic method using Taylor
      Couette flow allows us to efficiently fast shear-exfoliate graphite into large
      quantities of high-quality graphene sheets. Deposition of MnO2 on graphene is
      subsequently performed in a fluidic reactor within 10 min. The prepared
      MnO2/graphene nanocomposite shows outstanding electrochemical performances, such
      as a high specific capacitance of 679 F/g at 25 mV/s, a high rate capability of
      74.7% retention at an extremely high rate of 1000 mV/s, and an excellent cycling
      characteristic (~94.7% retention over 20 000 cycles). An asymmetric
      supercapacitor device is fabricated by assembling an anode of graphene and a
      cathode of MnO2/graphene, which resulted in high energy (35.2 W h/kg) and power
      (7.4 kW/kg) densities (accounting for the mass of both electrodes and the
      electrolyte) with a high rate capability and long cycle life.

PMID- 30289682
TI  - Applications of gamma,delta-Unsaturated Ketones Synthesized by Copper-Catalyzed
      Cascade Addition of Vinyl Grignard Reagents to Esters.
AB  - gamma,delta-Unsaturated ketones, so-called homoallylic ketones, have served as
      versatile building blocks for the synthesis of a variety of heterocycles,
      carbocycles, natural products, and reactive intermediates. Procured by a variety
      of processes, including conjugate addition of vinyl organometallic reagents to
      unsaturated ketones, allylation of silyl enol ethers, and rearrangements,
      homoallylic ketones are often synthesized by step-intensive methods. The cascade
      addition of 2 equiv of vinyl Grignard reagent to a carboxylate was reported by
      the Lubell laboratory in 2003 to give effective access to homoallylic ketones
      from a variety of aromatic, aliphatic, and alpha-amino methyl esters. Employing
      readily accessible vinyl magnesium halides in the presence of a catalytic amount
      of copper salt, this cascade reaction provides high yields of homoallylic ketones
      with minimal side product by a process featuring the assembly and collapse of a
      tetrahedral intermediate with expulsion of alkoxide ion, followed by conjugate
      addition to the resulting enone. Application of the cascade reaction to the
      synthesis of various homoallylic ketones has provided versatile building blocks
      for the synthesis of targets for different applications. For example, by
      employing (hetero)aryl di- and tricarboxylates as precursors, copper-catalyzed
      cascade additions have provided donor-acceptor and star-shaped monomers for
      optical-electronic materials. Amino ester starting materials have given
      homoallylic ketones for the synthesis of various peptidomimetics, including
      heteroarylalanines, hydroxyethylene isoesters, and diazepinone turn mimics.
      Moreover, anthranilate has served as building block to prepare various pyrrole,
      quinoline, benzodiazepine, and benzotriazepine heterocyles. In addition, cascade
      additions on hydroxyprolinates have given access to bipyrrole precursors of the
      prodigiosin family of natural products. In the interest to highlight the utility
      of the copper-catalyzed cascade addition of vinyl Grignard reagents to
      carboxylates, this Account provides details on the broad scope of substrates that
      deliver homoallylic ketone products as well as an overview of the wide range of
      applications in which this method may impact including materials and peptide
      science, heterocycle and natural product synthesis, and medicinal chemistry.

PMID- 30289683
TI  - Soft-Templated Synthesis of Lightweight, Elastic, and Conductive Nanotube
      Aerogels.
AB  - Conductive polymer (CP) nanotubes are fascinating nanostructures with high
      electrical conductivity, fast charge/discharge capability, and high mechanical
      strength. Despite these attractive physical properties, progress in the synthesis
      of CP nanotube hydrogels is still limited. Here, we report a facile and effective
      approach for the synthesis of polypyrrole (PPy) nanotube hydrogels by using the
      weakly interconnected network of self-assembled nanotubes of lithocholic acid as
      a soft template. The PPy nanotube hydrogels are then converted to aerogels by
      freeze drying, in which PPy nanotubes form elastic and conductive networks with a
      density of 38 mg/cm3 and an electrical conductivity of 1.13 S/m. The PPy nanotube
      aerogels are able to sustain a compressive strain as high as 70% and show an
      excellent cyclic compressibility due to their robust nanotube networks and
      hierarchically porous structures, which allow the compressive stress to be easily
      dissipated. Furthermore, PPy nanotube aerogels show negative strain-dependent
      electrical resistance changes under compressive strains. The lightweight,
      elastic, and conductive PPy nanotube aerogels may find potential applications in
      strain sensors, supercapacitors, and tissue scaffolds.

PMID- 30289684
TI  - Real-Time Accumbal Dopamine Response to Negative Stimuli: Effects of Ethanol.
AB  - Activity in the mesolimbic dopamine (DA) pathway is known to have a role in
      reward processing and related behaviors. The mesolimbic DA response to reward has
      been well-examined, while the response to aversive or negative stimuli has been
      studied to a lesser extent and produced inconclusive results. However, a brief
      increase in the DA concentration in terminals during nociceptive activation has
      become an established but not well-characterized phenomenon. Consequently, the
      interpretation of the significance of this neurochemical response is still
      elusive. The present study was designed to further explore these increases in
      subsecond DA dynamics triggered by negative stimuli using voltammetry in
      anesthetized rats. Our experiments revealed that repeated exposure to a tail
      pinch resulted in more efficacious DA release in rat nucleus accumbens. This fact
      may suggest a protective nature of immediate DA efflux. Furthermore, a sensitized
      DA response to a neutral stimulus, such as a touch, was discovered following
      several noxious pinches, while a touch applied before these pinches did not
      trigger DA release. Finally, it was found that the pinch-evoked DA efflux was
      significantly decreased by ethanol acutely administrated at an analgesic dose.
      Taken together, these results support the hypothesis that subsecond DA release in
      the nucleus accumbens may serve as an endogenous antinociceptive signal.

PMID- 30289686
TI  - Analysis of Short-Lived Reactive Species in Plasma-Air-Water Systems: The Dos and
      the Do Nots.
AB  - This Feature addresses the analysis of the reactive species generated by
      nonthermal atmospheric pressure plasmas, which are widely employed in industrial
      and biomedical research, as well as first clinical applications. We summarize the
      progress in detection of plasma-generated short-lived reactive oxygen and
      nitrogen species in aqueous solutions, discuss the potential and limitations of
      various analytical methods in plasma-liquid systems, and provide an outlook on
      the possible future research goals in development of short-lived reactive species
      analysis methods for a general nonspecialist audience.

PMID- 30289685
TI  - Preparation of Superhydrophilic Adsorbents with 3DOM Structure by Water-Soluble
      Colloidal Crystal Templates for Boron Removal from Natural Seawater.
AB  - Three-dimensionally ordered macroporous cross-linked poly(glycidyl methacrylate)
      (3DOM) was constructed by water-soluble colloidal crystal templates and further
      functionalized with N-methyl-d-glucamine (NMDG) to prepare superhydrophilic
      adsorbents for boron removal from natural seawater. 3DOM adsorbents possess
      features of interconnected macropore structure, ultrathin pore wall, and
      superhydrophilicity, making efficient adsorption possible. The effect of cross
      linking degree on the adsorption capacity toward boron was investigated. The NMDG
      modified 3DOM adsorbent with rich vicinal diol functional groups showed
      superhydrophilicity and outstanding performance of adsorption. Significantly, its
      adsorption effect in boron removal from natural seawater indicated that the
      concentration of boron in natural seawater could decline to 0.16 from 4.24 mg.L-1
      when the adsorbent dosage was 1 g.L-1, whereas the boron rejection reached 96.2%.
      After 10 regeneration-adsorption cycles, the adsorption capacity of 3DOM
      adsorbent remained over 85% of the initial value and the ordered structure was
      hardly changed. Additionally, 3DOM adsorbent could be directly and quickly
      separated from the seawater by a filter mesh of 16 mesh number. Research shows
      that the 3DOM adsorbent exhibits an adsorption performance for practical
      applications in boron removal from natural seawater.

PMID- 30289687
TI  - Development of Mannopyranoside Therapeutics against Adherent-Invasive Escherichia
      coli Infections.
AB  - Preventing bacterial adhesion to host cells is a provocative and alternative
      approach to traditional antibiotic treatments given the increasing microbial
      resistance. A brief overview of common antibiotic treatments is described in
      light of their respective resistance and remaining susceptibility. This strategy
      has been seriously considered in the context of adherent-invasive infections in
      Crohn's disease and urinary tract infections in particular. The adhesions of
      various pathogenic Escherichia coli strains to host cells are primarily mediated
      through carbohydrate-protein interactions involving bacterial organelles called
      fimbriae that can recognize specific glycoconjugate receptors on host cells. Of
      particular interest are the FimH and PapG fimbriae, which bind to mannosylated
      glycoproteins and glycolipids of the galabiose series, respectively. Therefore,
      blocking FimH- and PapG-mediated bacterial adhesion to uroepithelial cells by
      high-affinity carbohydrate antagonists constitutes a challenging therapeutic
      target of high interest. This is of particular interest since bacterial adhesion
      to host cells is a parameter unlikely to be the subject of bacterial mutations
      without affecting the carbohydrate ligand binding interactions at the basis of
      the recognition and infection processes. To date, there have been several
      families of potent FimH antagonists that include natural O-linked as well as
      unnatural analogues of alpha-d-mannopyranosides. These observations led to a
      thorough understanding of the intimate binding site interactions that helped to
      reveal the so-called "tyrosine gate mechanism" at the origin of the strong
      necessary interactions with sugar-possessing hydrophobic aglycones. By
      modification of the aglycones of single monosaccharidic d-mannopyranosides, it
      was possible to replace the natural complex oligomannoside structure by simpler
      ones. An appealing and successful series of analogues have been disclosed,
      including nanomolecular architectures such as dendrimers, polymers, and
      liposomes. In addition, the data were compared to the above multivalent
      architectures and confirmed the possibility of working with small sugar
      candidates. This Account primarily concentrates on the most promising types of
      FimH inhibitors belonging to the family of alpha-C-linked mannopyranosides.
      However, one of the drawbacks associated with C-mannopyranosides has been that
      they were believed to be in the inverted chair conformation, which is obviously
      not recognized by the E. coli FimH. To decipher this situation, various synthetic
      approaches, conformational aspects, and restrictions are discussed using
      molecular modeling, high-field NMR spectroscopy, and X-ray analysis. These
      combined techniques pointed to the fact that several alpha-C-linked
      mannopyranosides do exist in the required 4C1 chair conformation. Ultimately,
      recent findings in this growing field of interest culminated in the
      identification of drug candidates that have reached clinical phase I.

PMID- 30289689
TI  - Fluorescent Benzothiazinone Analogues Efficiently and Selectively Label Dpre1 in
      Mycobacteria and Actinobacteria.
AB  - Benzothiazinones (BTZ) are highly potent bactericidal inhibitors of mycobacteria
      and the lead compound, BTZ043, and the optimized drug candidate, PBTZ169, have
      potential for the treatment of tuberculosis. Here, we exploited the tractability
      of the BTZ scaffold by attaching a range of fluorophores to the 2-substituent of
      the BTZ ring via short linkers. We show by means of fluorescence imaging that the
      most advanced derivative, JN108, is capable of efficiently labeling its target,
      the essential flavoenzyme DprE1, both in cell-free extracts and after
      purification as well as in growing cells of different actinobacterial species.
      DprE1 displays a polar localization in Mycobacterium tuberculosis, M. marinum, M.
      smegmatis, and Nocardia farcinica but not in Corynebacterium glutamicum. Finally,
      mutation of the cysteine residue in DprE1 in these species, to which BTZ
      covalently binds, abolishes completely the interaction with JN108, thereby
      highlighting the specificity of this fluorescent probe.

PMID- 30289690
TI  - Stretching and Breaking of Ultrathin 2D Hybrid Organic-Inorganic Perovskites.
AB  - Two-dimensional (2D) hybrid organic-inorganic perovskites (HOIPs) are recent
      members of the 2D materials family with wide tunability, highly dynamic
      structural features, and excellent physical properties. Ultrathin 2D HOIPs and
      their heterostructures with other 2D materials have been exploited for study of
      physical phenomena and device applications. The in-plane mechanical properties of
      2D ultrathin HOIPs are critical for understanding the coupling between mechanical
      and other physical fields and for integrated devices applications. Here we report
      the in-plane mechanical properties of ultrathin freestanding 2D lead iodide
      perovskite membranes and their dependence on the membrane thickness. The in-plane
      Young's moduli of 2D HOIPs are smaller than that of conventional covalently
      bonded 2D materials. As the thickness increases from monolayer to three-layer,
      both the Young's modulus and breaking strength decrease, while three-layer and
      four-layer 2D HOIPs have almost identical in-plane mechanical properties. These
      thickness-dependent mechanical properties can be attributed to interlayer
      slippage during deformation. Our results show that ultrathin 2D HOIPs exhibit
      outstanding breaking strength/Young's modulus ratio compared to many other widely
      used engineering materials and polymeric flexible substrates, which renders them
      suitable for application into flexible electronic devices.

PMID- 30289688
TI  - Ligand Density and Nanoparticle Clustering Cooperate in the Multivalent
      Amplification of Epidermal Growth Factor Receptor Activation.
AB  - Multivalent presentation of ligands on nanoparticles (NPs) is considered a
      general strategy for enhancing receptor binding and activation through
      amplification of ligand-receptor interactions within the footprint of the
      individual NPs. The spatial clustering of ligand-functionalized NPs represents an
      additional, less well understood mechanism for increasing local ligand-receptor
      interactions, especially for receptors that form higher-order assemblies, such as
      the epidermal growth factor (EGF) receptor (EGFR). To shed light on the interplay
      between ligand density ( i.e., multivalency) and NP clustering in signal
      amplification, we apply EGF-functionalized 72 +/- 1 nm gold nanoparticles (NP
      EGF) with known ligand loading (10-200 EGF/NP) as quantifiable and experimentally
      tractable units of EGFR activation and characterize the NP-mediated amplification
      of EGFR phosphorylation as a function of both EGF surface density and NP-EGF
      clustering for two cancer cell lines (HeLa and MDA-MB-468). The measurements
      confirm a strong multivalent amplification of EGFR phosphorylation through NP-EGF
      on the cellular level that results in EGF-loading-dependent maximum EGFR
      phosphorylation levels. A microscopic analysis of NP-EGF-induced EGFR
      phosphorylation reveals a heterogeneous spatial distribution of EGFR activation
      across the cell surface. Clustering of multivalent NP-EGF on sub-diffraction
      limited length scales is found to result in a local enhancement of EGFR
      phosphorylation in signaling "hot spots" from where the signal can spread
      laterally in an EGF-independent fashion. Increasing EGF loadings of the NP
      enhances NP-EGF clustering and intensifies EGFR phosphorylation. These
      observations suggest that NP-EGF clustering and the associated local enhancement
      of ligand-receptor interactions are intrinsic components of the multivalent
      amplification of phosphorylation for the heterogeneously distributed EGFR through
      NP-EGF.

PMID- 30289691
TI  - A Diverted Aerobic Heck Reaction Enables Selective 1,3-Diene and 1,3,5-Triene
      Synthesis through C-C Bond Scission.
AB  - Substituted 1,3-dienes are valuable synthetic intermediates used in myriad
      catalytic transformations, yet modern catalytic methods for their preparation in
      a highly modular fashion using simple precursors are relatively few. We report
      here an aerobic boron Heck reaction with cyclobutene that forms exclusively
      linear 1-aryl-1,3-dienes using (hetero)arylboronic acids, or 1,3,5-trienes using
      alkenylboronic acids, rather than typical Heck products (i.e., substituted
      cyclobutenes). Experimental and computational mechanistic data support a
      pericyclic mechanism for C-C bond cleavage that enables the cycloalkene to
      circumvent established limitations associated with diene reagents in Heck-type
      reactions.

PMID- 30289692
TI  - Discovery and Characterization of a Thioesterase-Specific Monoclonal Antibody
      That Recognizes the 6-Deoxyerythronolide B Synthase.
AB  - Assembly line polyketide synthases (PKSs) are large multimodular enzymes
      responsible for the biosynthesis of diverse antibiotics in bacteria. Structural
      and mechanistic analysis of these megasynthases can benefit from the discovery of
      reagents that recognize individual domains or linkers in a site-specific manner.
      Monoclonal antibodies not only have proven themselves as premier tools in
      analogous applications but also have the added benefit of constraining the
      conformational flexibility of their targets in unpredictable but often useful
      ways. Here we have exploited a library based on the naive human antibody
      repertoire to discover a Fab (3A6) that recognizes the terminal thioesterase (TE)
      domain of the 6-deoxyerythronolide B synthase with high specificity. Biochemical
      assays were used to verify that 3A6 binding does not inhibit enzyme turnover. The
      co-crystal structure of the TE-3A6 complex was determined at 2.45 A resolution,
      resulting in atomic characterization of this protein-protein recognition
      mechanism. Fab binding had minimal effects on the structural integrity of the TE.
      In turn, these insights were used to interrogate via small-angle X-ray scattering
      the solution-phase conformation of 3A6 complexed to a catalytically competent PKS
      module and bimodule. Altogether, we have developed a high-affinity monoclonal
      antibody tool that recognizes the TE domain of the 6-deoxyerythronolide B
      synthase while maintaining its native function.

PMID- 30289693
TI  - Rare-Earth-Doped Ceria Systems and Their Performance as Solid Electrolytes: A
      Puzzling Tangle of Structural Issues at the Average and Local Scale.
AB  - Rare-earth (RE)-doped ceria systems, in particular when RE = Nd, Sm, or Gd, are
      well-known to be characterized by high values of ionic conductivity in the
      intermediate temperature range, which, in principle, makes them ideal solid
      electrolytes in solid oxide fuel and electrolysis cells. Defect chemistry turns
      out to be a pivotal issue in this framework because ionic conductivity is driven
      by the ability of oxygen vacancies to move through the lattice, and any form of
      defect clustering tends to depress the efficiency of oxygen transport. In this
      viewpoint, not only are factors at the average scale assessed, such as the
      compositional extent of the CeO2-like solid solution, but also the occurrence of
      local inhomogeneities due to vacancy-dopant association is discussed in
      correlation with its central role in hindering the migration of vacancies. The
      relationship between the stability of the hybrid phase and the RE3+ ionic size is
      presented, and the highly complementary role of Raman spectroscopy toward X-ray
      diffraction is described in detail. The key points of the whole discussion are
      finally used to identify the most relevant structure-related parameters affecting
      ionic conductivity in the studied material.

PMID- 30289694
TI  - Small Structural Variations Have Large Effects on the Assembly Properties and
      Spin State of Room Temperature High Spin Fe(II) Iminopyridine Cages.
AB  - Small changes in steric bulk at the terminus of bis-iminopyridine ligands can
      effect large changes in the spin state of self-assembled Fe(II)-iminopyridine
      cage complexes. If the added bulk is properly matched with ligands that are
      either sufficiently flexible to allow twisted octahedral geometries at the Fe
      centers or can assemble with unusual mer configurations at the metals, room
      temperature high spin Fe(II) cages can be synthesized. These complexes maintain
      their high spin state in solution at low temperatures and have been characterized
      by X-ray crystallographic and computational methods. The high spin M2L3 meso
      helicate and M4L6 cage complexes display longer N-Fe bond distances and larger
      interligand N-Fe-N bond angles than their diamagnetic counterparts, and these
      structural changes invert the ligand selectivity in narcissistic self-sorting and
      accelerate subcomponent exchange rates. The paramagnetic cages can be easily
      converted to diamagnetic cages by subcomponent exchange under mild conditions,
      and the intermediates of the exchange process can be visualized in situ by NMR
      analysis.

PMID- 30289695
TI  - Nanofibers with Incorporated Autochthonous Bacteria as Potential Probiotics for
      Local Treatment of Periodontal Disease.
AB  - The conventional treatment of periodontal disease does not solve the high
      incidence of recolonization of periodontal pockets by pathogens. Here, we
      introduce an innovative concept of incorporating autochthonous bacteria as
      potential probiotics into nanofibers for local treatment. We selected and
      isolated the strain 25.2.M from the oral microbiota of healthy volunteers. It was
      identified as Bacillus sp. based on 16S rRNA sequence analyses. The strain is
      nonpathogenic, produces antimicrobial substances, and can grow over the
      periodontal pathogen Aggregatibacter actinomycetemcomitans in vitro, making it a
      promising probiotic candidate. The strain 25.2.M was successfully incorporated
      into the nanofibers in the form of spores (107 CFU/mg), the viabilities of which
      were exceptional (max. change of 1 log unit) both during electrospinning and
      after 12 months of storage. The release of the bacteria was delayed from
      chitosan/poly(ethylene oxide) compared to poly(ethylene oxide) nanofibers, and
      the antimicrobial activity against A. actinomycetemcomitans was confirmed. The
      developed nanodelivery system for administration into periodontal pockets thus
      offers a promising approach for the inhibition of periodontal pathogens and
      restoration of healthy oral microbiota.

PMID- 30289696
TI  - Synthesis and Characterization of a Water Stable Uranyl(V) Complex.
AB  - We have identified a polydentate aminocarboxylate ligand that stabilizes
      uranyl(V) in water. The mononuclear [UO2(dpaea)]X, (dpaeaH2 = Bis(pyridyl-6
      methyl-2-carboxylate)-ethylamine; X = CoCp2*+ or X = K(2.2.2.cryptand) complexes
      have been isolated from anaerobic organic solution, crystallographically and
      spectroscopically characterized both in water and organic solution. These
      complexes disproportionate at pH <= 6, but are stable in anaerobic water at pH 7
      10 for several days.

PMID- 30289697
TI  - Antiparallel Coiled-Coil Interactions Mediate the Homodimerization of the DNA
      Damage-Repair Protein PALB2.
AB  - Deficits in DNA damage-repair pathways are the root cause of several human
      cancers. In mammalian cells, DNA double-strand break repair is carried out by
      multiple mechanisms, including homologous recombination (HR). The partner and
      localizer of BRCA2 (PALB2), which is an essential factor for HR, binds to the
      breast cancer susceptibility 1 (BRCA1) protein at DNA double-strand breaks. At
      the break site, PALB2 also associates with the breast cancer susceptibility 2
      (BRCA2) protein to form a multiprotein complex that facilitates HR. The BRCA1
      PALB2 interaction is mediated by association of predicted helical coiled-coil
      regions in both proteins. PALB2 can also homodimerize through the formation of a
      coiled coil by the self-association of helical elements at the N-terminus of the
      PALB2 protein, and this homodimerization has been proposed to regulate the
      efficiency of HR. We have produced a segment of PALB2, designated PALB2cc (PALB2
      coiled coil segment) that forms alpha-helical structures, which assemble into
      stable homodimers. PALB2cc also forms heterodimers with a helical segment of
      BRCA1, called BRCA1cc (BRCA1 coiled coil segment). The three-dimensional
      structure of the homodimer formed by PALB2cc was determined by solution NMR
      spectroscopy. This PALB2cc homodimer is a classical antiparallel coiled-coil
      leucine zipper. NMR chemical-shift perturbation studies were used to study dimer
      formation for both the PALB2cc homodimer and the PALB2cc/BRCA1cc heterodimer. The
      mutation of residue Leu24 of PALB2cc  significantly reduces its homodimer
      stability, but has a more modest effect on the stability of the heterodimer
      formed between PALB2cc and BRCA1cc. We show that mutation of Leu24 leads to
      genomic instability and reduced cell viability after treatment with agents that
      induce DNA double-strand breaks. These studies may allow the identification of
      distinct mutations of PALB2cc that selectively disrupt homodimeric versus
      heterodimeric interactions, and reveal the specific role of PALB2cc
      homodimerization in HR.

PMID- 30289698
TI  - Life Cycle Greenhouse Gas Emissions and Costs of Production of Diesel and Jet
      Fuel from Municipal Solid Waste.
AB  - This paper quantifies and compares the life cycle GHG emissions and costs of
      production of diesel and jet fuel derived from municipal solid waste (MSW) in the
      United States via three thermochemical conversion pathways: conventional
      gasification and Fischer-Tropsch (FT middle distillate, MD), plasma gasification
      and Fischer-Tropsch (Plasma FT MD), and conventional gasification, catalytic
      alcohol synthesis, and alcohol-to-jet upgrading (ATJ MD). We use expanded system
      boundaries to capture the change in existing MSW use and disposal, and account
      for parameter uncertainty with Monte Carlo simulations. We estimate median life
      cycle GHG emissions of 32.9, 62.3, and 52.7 gCO2e/MJ for FT, Plasma FT and ATJ MD
      fuels, respectively, compared to a baseline of 90 gCO2e/MJ for conventional MD
      fuels. Median minimum selling prices are estimated at 0.99, 1.78, and 1.20 $ per
      liter with the probability of achieving a positive net present value of fuel
      production at market prices of 14%, 0.1% and 7% for FT, Plasma FT and ATJ MD
      fuels, respectively. If the societal perspective rather than an investor's
      perspective is evaluated, then the probability of positive net present value of
      fuel production increases to 93%, 67%, and 92.5% for the FT, Plasma FT, and ATJ
      MD fuels, respectively.

PMID- 30289699
TI  - Fully Conjugated [4]Chrysaorene. Redox-Coupled Anion Binding in a Tetraradicaloid
      Macrocycle.
AB  - [4]Chrysaorene, a fully conjugated carbocyclic coronoid, is shown to be a low
      bandgap pi-conjugated system with a distinct open-shell character. The system
      shows good chemical stability and can be oxidized to well-defined radical cation
      and dication states. The cavity of [4]chrysaorene acts as an anion receptor
      toward halide ions with a particular selectivity toward iodides ( Ka = 207 +/- 6
      M-1). The interplay between anion binding and redox chemistry is demonstrated
      using a 1H NMR analysis in solution. In particular, a well-resolved,
      paramagnetically shifted spectrum of the [4]chrysaorene radical cation is
      observed, providing evidence for the inner binding of the iodide. The radical
      cation-iodide adduct can be generated in thin solid films of [4] chrysaorene by
      simple exposure to diiodine vapor.

PMID- 30289700
TI  - Identification and Quantitative Analysis of 2-Methyl-4-propyl-1,3-oxathiane in
      Wine.
AB  - On the basis of the chemistry of wine and the co-occurrence of 3-sulfanylhexan-1
      ol (3-SH) and acetaldehyde, we investigated the existence of 2-methyl-4-propyl
      1,3-oxathiane (1) and identified the presence of a single detectable geometric
      isomer, cis-1, in wines for the first time. A stable isotope dilution assay
      (SIDA) using headspace-solid-phase microextraction (HS-SPME) and gas
      chromatography-mass spectrometry (GC-MS) was developed and validated, and used to
      quantitate cis-1 in a survey of wines, revealing a range from undetectable (limit
      of detection = 2.6 ng/L) to 460 ng/L. The odor detection threshold of 1 (using a
      standard comprising 85% cis-1 and 15% trans-1) in neutral white wine was
      determined to be 7.1 MUg/L. Despite cis-1 not appearing above the determined
      sensory threshold in the studied wines, the findings demonstrated the presence of
      a new volatile sulfur compound with a strong correlation to 3-SH concentration (
      r = 0.72), showing that cis-1 has potential implications for the fate of the
      important wine aroma compound 3-SH.

PMID- 30289701
TI  - Controlling the Morphology of Au-Pd Heterodimer Nanoparticles by Surface Ligands.
AB  - Controlling the morphology of noble-metal nanoparticles is mandatory to tune
      specific properties such as catalytic and optical behavior. Heterodimers
      consisting of two noble metals have been synthesized, so far mostly in aqueous
      media using selective surfactants or chemical etching strategies. We report a
      facile synthesis for Au@Pd and Pd@Au heterodimer nanoparticles (NPs) with
      morphologies ranging from segregated domains (heteroparticles) to core-shell
      structures by applying a seed-mediated growth process with Au and Pd seed
      nanoparticles in 1-octadecene (ODE), which is a high-boiling organic solvent. The
      as-synthesized oleylamine (OAm) functionalized Au NPs led to the formation of OAm
      Au@Pd heteroparticles with a "windmill" morphology, having an Au core and Pd
      "blades". The multiply twinned structure of the Au seed particles (? ~ 9-11 nm)
      is associated with a reduced barrier for heterogeneous nucleation. This leads to
      island growth of bimetallic Au@Pd heteroparticles with less-regular morphologies.
      The reaction process can be controlled by tuning the surface chemistry with
      organic ligands. Functionalization of Au NPs (O ~ 9-11 nm) with 1-octadecanethiol
      (ODT) led to the formation of ODT-Au@Pd NPs with a closed Pd shell through a
      strong ligand-metal binding, which is accompanied by a redistribution of the
      electron density. Experiments with varied Pd content revealed surface epitaxial
      growth of Pd on Au. For OAm-Pd and ODT-Pd seed particles, faceted, Au-rich domain
      NPs and impeded core-shell NPs were obtained, respectively. This is related to
      the high surface energy of the small Pd seed particles (? ~ 5-7 nm). The metal
      distribution of all bimetallic NPs was analyzed by extended (aberration
      corrected) transmission electron microscopy (HR-TEM, HAADF-STEM, EDX mapping,
      ED). The Au and Pd NPs, as well as the ODT-Au@Pd and OAm-Pd@Au heteroparticles,
      catalyze the reduction of 4-nitrophenol to 4-aminophenol with borohydride. The
      catalytic activity is dictated by the particle structure. OAm-Au@Pd
      heteroparticles with faceted Au domains had the highest activity because of a
      mixed Au-Pd surface structure, while ODT-Au@Pd NPs, where the active Au core is
      covered by a Pd shell, had the lowest activity.

PMID- 30289703
TI  - Evolutionarily Conserved Allosteric Communication in Protein Tyrosine
      Phosphatases.
AB  - Protein tyrosine phosphatases (PTPs) are an important class of regulatory enzymes
      that exhibit aberrant activities in a wide range of diseases. A detailed mapping
      of allosteric communication in these enzymes could, thus, reveal the structural
      basis of physiologically relevant-and, perhaps, therapeutically informative
      perturbations (i.e., mutations, post-translational modifications, or binding
      events) that influence their catalytic states. This study combines detailed
      biophysical studies of protein tyrosine phosphatase 1B (PTP1B) with bioinformatic
      analyses of the PTP family to examine allosteric communication in this class of
      enzymes. Results of X-ray crystallography, molecular dynamics simulations, and
      sequence-based statistical analyses indicate that PTP1B possesses a broadly
      distributed allosteric network that is evolutionarily conserved across the PTP
      family, and findings from both kinetic studies and mutational analyses show that
      this network is functionally intact in sequence-diverse PTPs. The allosteric
      network resolved in this study reveals new sites for targeting allosteric
      inhibitors of PTPs and helps explain the functional influence of a diverse set of
      disease-associated mutations.

PMID- 30289702
TI  - Self-Assembly of Supramolecular Fractals from Generation 1 to 5.
AB  - In the seeking of molecular expression of fractal geometry, chemists have
      endeavored in the construction of molecules and supramolecules during the past
      few years, while only a few examples were reported, especially for the discrete
      architectures. We herein designed and constructed five generations of
      supramolecular fractals (G1-G5) based on the coordination-driven self-assembly of
      terpyridine ligands. All the ligands were synthesized from triphenylamine motif,
      which played a central role in geometry control. Different approaches based on
      direct Sonogashira coupling and/or ?tpy-Ru(II)-tpy? connectivity were employed to
      prepare complex Ru(II)-organic building blocks. Fractals G1-G5 were obtained in
      high yields by precise coordination of organic or Ru(II)-organic building blocks
      with Zn(II) ions. Characterization of those architectures were accomplished by 1D
      and 2D NMR spectroscopy, electrospray ionization mass spectrometry (ESI-MS),
      traveling-wave ion mobility mass spectrometry (TWIM-MS), and transmission
      electron microscopy (TEM). Furthermore, the two largest fractals also
      hierarchically self-assemble into ordered supramolecular nanostructures either at
      solid/liquid interface or in solution on the basis of their well-defined
      scaffolds.

PMID- 30289704
TI  - Best of Two Worlds? How MD Simulations of Amphiphilic Helical Peptides in
      Membranes Can Complement Data from Oriented Solid-State NMR.
AB  - The membrane alignment of helical amphiphilic peptides in oriented phospholipid
      bilayers can be obtained as ensemble and time averages from solid state 2H NMR by
      fitting the quadrupolar splittings to ideal alpha-helices. At the same time,
      molecular dynamics (MD) simulations can provide atomistic insight into peptide
      membrane systems. Here, we evaluate the potential of MD simulations to complement
      the experimental NMR data that is available on three exemplary systems: the
      natural antimicrobial peptide PGLa and the two designer-made peptides MSI-103 and
      KIA14, whose sequences were derived from PGLa. Each peptide was simulated for 1
      MUs in a DMPC lipid bilayer. We calculated from the MD simulations the local
      angles which define the side chain geometry with respect to the peptide helix.
      The peptide orientation was then calculated (i) directly from the simulation,
      (ii) from back-calculated MD-derived NMR splittings, and (iii) from experimental
      2H NMR splittings. Our findings are that (1) the membrane orientation and
      secondary structure of the peptides found in the NMR analysis are generally well
      reproduced by the simulations; (2) the geometry of the side chains with respect
      to the helix backbone can deviate significantly from the ideal structure
      depending on the specific residue, but on average all side chains have the same
      orientation; and (3) for all of our peptides, the azimuthal rotation angle found
      from the MD-derived splittings is about 15 degrees  smaller than the experimental
      value.

PMID- 30289705
TI  - Smart Polymersomes Dually Functionalized with cRGD and Fusogenic GALA Peptides
      Enable Specific and High-Efficiency Cytosolic Delivery of Apoptotic Proteins.
AB  - Low cell selectivity and uptake coupled with endosomal entrapment pose critical
      hurdles for intracellular delivery and clinical translation of therapeutic
      proteins. Herein, we report that smart polymersomes dually functionalized with
      cRGD and fusogenic GALA peptides (cRGD/GALA-Ps) enable alphanubeta3-specific and
      high-efficiency cytosolic delivery of cytochrome C (CC), a model apoptotic
      protein, to A549 human lung cancer cells. cRGD/GALA-Ps was prepared with 20 mol %
      cRGD and varying GALA contents from 2 to 4 to 6 mol % via coassembly of PEG- b
      poly(trimethylene carbonate- co-dithiolane trimethylene carbonate)-spermine (PEG-
      b-P(TMC- co-DTC)-spermine), cRGD-PEG- b-P(TMC- co-DTC), and maleimide-PEG- b
      P(TMC- co-DTC) and postmodification using GALA-SH (sequence:
      CWEAALAEALAEALAEHLAEALAEALEALAA). cRGD/GALA-Ps loaded with ~13 wt % CC displayed
      a small size of about 65 nm and fast glutathione-triggered protein release.
      Interestingly, cRGD/GALA-Ps maintained a similar targeting ability to cRGD-Ps in
      alphanubeta3-positive A549 lung cancer cells, while markedly enhanced cytosolic
      release of FITC-labeled CC, as revealed by confocal microscopy. MTT assays
      exhibited that CC-loaded cRGD/GALA-Ps was significantly more potent than CC
      loaded cRGD-Ps, in which cell viabilities of 76.2, 51.0, 29.6, and 35.5% were
      discerned for cRGD/GALA-Ps with 0, 2, 4, and 6 mol % GALA, respectively, at 15.4
      MUM CC. Apoptosis assays corroborated that cRGD/GALA-Ps-CC with 4 mol % GALA
      induced better apoptosis of A549 cells than cRGD-Ps-CC (cell apoptosis: 36.4 vs
      14.4%). These results highlight that dual-functionalization of polymersomes with
      targeting and fusogenic peptides provides an appealing strategy for cytosolic
      protein delivery.

PMID- 30289706
TI  - Lipid- and Cholesterol-Mediated Time-Scale-Specific Modulation of the Outer
      Membrane Protein X Dynamics in Lipid Bilayers.
AB  - Membrane protein function fundamentally depends on lipid-bilayer fluidity and the
      composition of the biological membrane. Although dynamic interdependencies
      between membrane proteins and the surrounding lipids are suspected, a detailed
      description is still missing. To uncover lipid-modulated membrane protein
      backbone dynamics, time-scale-specific NMR relaxation experiments with residue
      resolution were recorded. The data revealed that lipid order, modified either
      biochemically or biophysically, changes the dynamics of the immersed membrane
      protein in a specific and time-scale-dependent manner. A temperature-dependent
      dynamics analysis furthermore suggests a direct coupling between lipid and
      protein dynamics in the picosecond-nanosecond, microsecond, and millisecond time
      scales, caused by the lipid's trans-gauche isomerization, the segmental and
      rotational motion of lipids, and the fluidity of the lipid phase, respectively.
      These observations provide evidence of a direct modulatory capability of the
      membrane to regulate protein function through lipid dynamics ranging from
      picoseconds to milliseconds.

PMID- 30289707
TI  - Structural Approach To Identify a Lead Scaffold That Targets the Translesion
      Synthesis Polymerase Rev1.
AB  - Translesion synthesis (TLS) is a mechanism of replication past damaged DNA
      through which multiple forms of human cancer survive and acquire resistance to
      first-line genotoxic chemotherapies. As such, TLS is emerging as a promising
      target for the development of a new class of anticancer agents. The C-terminal
      domain of the DNA polymerase Rev1 (Rev1-CT) mediates assembly of the functional
      TLS complex through protein-protein interactions (PPIs) with Rev1 interacting
      regions (RIRs) of several other TLS DNA polymerases. Utilizing structural
      knowledge of the Rev1-CT/RIR interface, we have identified the phenazopyridine
      scaffold as an inhibitor of this essential TLS PPI. We demonstrate direct binding
      of this scaffold to Rev1-CT, and the synthesis and evaluation of a small series
      of analogues have provided important structure-activity relationships for further
      development of this scaffold. Furthermore, we utilized the umbrella sampling
      method to predict the free energy of binding to Rev1-CT for each of our
      analogues. Binding energies calculated through umbrella sampling correlated well
      with experimentally determined IC50 values, validating this computational tool as
      a viable approach to predict the biological activity for inhibitors of the Rev1
      CT/RIR PPI.

PMID- 30289708
TI  - Crystalline 2D Covalent Organic Framework Membranes for High-Flux Organic Solvent
      Nanofiltration.
AB  - Two-dimensional (2D) covalent organic framework (COF) materials have the most
      suitable microstructure for membrane applications in order to achieve both high
      flux and high selectivity. Here, we report the synthesis of a crystalline TFP-DHF
      2D COF membrane constructed from two precursors of 1,3,5-triformylphloroglucinol
      (TFP) and 9,9-dihexylfluorene-2,7-diamine (DHF) through the Langmuir-Blodgett
      (LB) method, for the first timed. A single COF layer is precisely four unit cells
      thick and can be transferred to different support surfaces layer by layer. The
      TFP-DHF 2D COF membrane supported on an anodic aluminum oxide (AAO) porous
      support displayed remarkable permeabilities for both polar and nonpolar organic
      solvents, which were approximately 100 times higher than that of the amorphous
      membranes prepared by the same procedure and similar to that for the best of the
      reported polymer membranes. The transport mechanism through the TFP-DHF 2D COF
      membrane was found to be a viscous flow coupled with a strong slip boundary
      enhancement, which was also different from those of the amorphous polymer
      membranes. The membrane exhibited a steep molecular sieving with a molecular
      weight retention onset (MWRO) of approximately 600 Da and a molecular weight
      cutoff (MWCO) of approximately 900 Da. The substantial performance enhancement
      was attributed to the structural change from an amorphous structure to a well
      defined ordered porous structure, which clearly demonstrated the high potential
      for the application of 2D COFs as the next generation of membrane materials.

PMID- 30289709
TI  - Ni-Catalyzed Cross-Coupling of Dimethyl Aryl Amines with Arylboronic Esters under
      Reductive Conditions.
AB  - Herein, we reported a successful Suzuki-Miyaura coupling of dimethyl aryl amines
      to forge biaryl skeleton via Ni catalysis in the absence of directing groups and
      preactivation. This transformation proceeded with high efficiency in the presence
      of magnesium. Preliminary mechanism studies demonstrated dual roles of magnesium:
      (i) a reductant that reduced Ni(II) species to active Ni(I) catalyst; (ii) a
      unique promoter that facilitated the Ni(I)/Ni(III) catalytic cycle.

PMID- 30289711
TI  - Hue Parameter Fluorescence Identification of Edible Oils with a Smartphone.
AB  - Food fraud can be highly lucrative, and high accuracy authentication of various
      foodstuffs is becoming essential. Olive oil is one of the most investigated food
      matrices, due to its high price and low production globally, with recent food
      fraud examples showing little or no high quality olive oil in the tested oils.
      Here a simple method using a 405 nm LED flashlight and a smartphone is developed
      for edible oil authentication. Identification is fingerprinted by intrinsic
      fluorescent compounds in the oils, such as chlorophylls and polyphenols. This
      study uses the hue parameter of HSV-colorspace to authenticate 24 different
      edible oils of 9 different types and 15 different brands. For extra virgin olive
      oil, all nine samples are well separated from the other oil samples. The rest of
      the samples were also well type-distinguished by the hue parameter, which is
      complemented by hue-histogram analysis. This opens up opportunities for low-cost
      and high-throughput smartphone field-testing of edible oils on all levels of the
      production and supply chain.

PMID- 30289710
TI  - Automated Topology Builder Version 3.0: Prediction of Solvation Free Enthalpies
      in Water and Hexane.
AB  - The ability of atomic interaction parameters generated using the Automated
      Topology Builder and Repository version 3.0 (ATB3.0) to predict experimental
      hydration free enthalpies (Delta Gwater) and solvation free enthalpies in the
      apolar solvent hexane (Delta Ghexane) is presented. For a validation set of 685
      molecules the average unsigned error (AUE) between Delta Gwater values calculated
      using the ATB3.0 and experiment is 3.8 kJ.mol-1. The slope of the line of best
      fit is 1.00, the intercept -1.0 kJ.mol-1, and the R2 0.90. For the more
      restricted set of 239 molecules used to validate OPLS3 ( J. Chem. Theory Comput.
      2016 , 12 , 281 - 296 , DOI: 10.1021/acs.jctc.5b00864 ) the AUE using the ATB3.0
      is just 2.7 kJ.mol-1 and the R2 0.93. A roadmap for further improvement of the
      ATB parameters is presented together with a discussion of the challenges of
      validating force fields against the available experimental data.

PMID- 30289712
TI  - Reproducibility of Free Energy Calculations across Different Molecular Simulation
      Software Packages.
AB  - Alchemical free energy calculations are an increasingly important modern
      simulation technique to calculate free energy changes on binding or solvation.
      Contemporary molecular simulation software such as AMBER, CHARMM, GROMACS, and
      SOMD include support for the method. Implementation details vary among those
      codes, but users expect reliability and reproducibility, i.e., for a given
      molecular model and set of force field parameters, comparable free energy
      differences should be obtained within statistical bounds regardless of the code
      used. Relative alchemical free energy (RAFE) simulation is increasingly used to
      support molecule discovery projects, yet the reproducibility of the methodology
      has been less well tested than its absolute counterpart. Here we present RAFE
      calculations of hydration free energies for a set of small organic molecules and
      demonstrate that free energies can be reproduced to within about 0.2 kcal/mol
      with the aforementioned codes. Absolute alchemical free energy simulations have
      been carried out as a reference. Achieving this level of reproducibility requires
      considerable attention to detail and package-specific simulation protocols, and
      no universally applicable protocol emerges. The benchmarks and protocols reported
      here should be useful for the community to validate new and future versions of
      software for free energy calculations.

PMID- 30289713
TI  - Structurally Diverse Sesquiterpenoids from the Endangered Ornamental Plant
      Michelia shiluensis.
AB  - A preliminary phytochemical investigation on the MeOH extract of the leaves and
      twigs of the endangered ornamental plant Michelia shiluensis led to the isolation
      of 16 sesquiterpenoids. The isolated compounds comprised germacrane- (1-4, 13,
      14), guaiane- (5-9, 15), amorphane- (10), and eudesmane-type (11, 12, 16)
      sesquiterpenoids. The new structures (1-12) were elucidated by spectroscopic and
      computational methods, and their absolute configurations (except for 9) were
      assigned by single-crystal X-ray diffraction crystallographic data and/or
      electronic circular dichroism spectra. Shiluolides (A-D, 1-4) are unprecedented
      C16 or C17 homogermacranolides, and their putative biosynthetic pathways are
      briefly discussed. Shiluone D (8) is a rare 1,10- seco-guaiane sesquiterpenoid
      featuring a new ether-containing spirocyclic ring, whereas shiluone E (9)
      represents the first example of a 1,5-4,5-di- seco-guaiane with a rare 5,11 
      lactone moiety. Shiluone F (10) is the first amorphane-type sesquiterpenoid
      possessing an oxetane ring bridging C-1 and C-7. Bioassay evaluations indicated
      that lipiferolide (13) showed noteworthy cytotoxicities toward human cancer cell
      lines MCF-7 and A-549, with IC50 values of 1.5 and 7.3 MUM, respectively.
      Shiluone D (8) exerted inhibition against protein tyrosine phosphatase 1B (IC50:
      46.3 MUM).

PMID- 30289714
TI  - Prevention and Disintegration of Human Serum Albumin Fibrils under Physiological
      Conditions: Biophysical Aspects.
AB  - An anomaly in the protein folding process can lead to aggregation or fibrillation
      of proteins which has been related to neurodegenerative and peripheral diseases.
      Therefore, it is important to understand the mechanism of prevention of
      aggregation/fibrillation and to design suitable inhibitors for this process.
      Literature information suggests that most of the work on these systems has been
      done on heat induced fibrils (57-65  degrees C). As a step ahead, in the present
      study, efforts have been made to understand the inhibition process under
      physiological conditions (37  degrees C, pH 7.4), which is more relevant to the
      fibrils formed under natural cellular environment. The qualitative and
      quantitative aspects of the interactions of the surfactant sodium dodecyl
      sulphate (SDS) and antiinflammatory drug diclofenac sodium (DCF) with human serum
      albumin at different stages of the fibrillation process have been studied
      employing a combination of spectroscopic, calorimetric, and microscopic
      techniques. Fibril formation understudied conditions was confirmed by
      transmission electron microscopy images and thioflavin T binding assay along with
      dynamic light scattering measurements. Energetics from isothermal titration
      calorimetry provided insights into the nature of interactions and the mechanism
      of inhibition. We found inhibition efficiency of the additives in the order,
      micellar SDS > 45 mM DCF > monomeric SDS > 5 mM DCF. The energetics of
      interaction, correlated with the molecular structure of inhibitors provides
      guidelines for effective synthesis and design of inhibitors. ITC results have
      imparted important relationship between inhibition efficiency and exothermicity
      of interactions and have demonstrated the significance of polar interactions in
      fibril prevention by these inhibitors. Interestingly it was found that the
      micellar SDS not only inhibits the process but also effectively disintegrates the
      formed fibrils.

PMID- 30289715
TI  - ASV-ID, a Proteogenomic Workflow to Predict Candidate Protein Isoforms based on
      Transcript Evidence.
AB  - One of the goals of the Chromosome-centric Human Proteome Project (C-HPP) is to
      map and characterize the functions of protein isoforms produced by alternative
      splicing of genes. However, identifying alternative splice variants (ASVs) via
      mass spectrometry remains a major challenge, because ASVs usually contain highly
      homologous peptide sequences. A routine protein sequence analysis suggests that
      more than half of the investigated proteins do not generate two or more uniquely
      mapping peptides that would enable their isoforms to be distinguished. Here, we
      develop a new proteogenomics method, named "ASV-ID" (alternative splicing
      variants identification), which enables identification of ASVs by using a cell
      type-specific protein sequence database that is supported by RNA-Seq data. Using
      this workflow, we identify 1,935 distinct proteins under highly stringent
      conditions. In fact, transcript evidence on these 841 proteins helps us
      distinguish them from other isoforms, despite the fact that these proteins are
      not predicted to make 2 or more uniquely mapping peptides. We also demonstrate
      that ASV-ID enables detection of 19 differently expressed isoforms present in
      several cell lines. Thus, a new workflow using ASV-ID has the potential to map
      yet-to-be-identified difficult protein isoforms in a simple and robust way.

PMID- 30289716
TI  - Design and Activity of Specific Hypoxia-Inducible Factor-2alpha (HIF-2alpha)
      Inhibitors for the Treatment of Clear Cell Renal Cell Carcinoma: Discovery of
      Clinical Candidate ( S)-3-((2,2-Difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro
      1 H-inden-4-yl)oxy)-5-fluorobenzonitrile (PT2385).
AB  - HIF-2alpha, a member of the HIF family of transcription factors, is a key
      oncogenic driver in cancers such as clear cell renal cell carcinoma (ccRCC). A
      signature feature of these cancers is the overaccumulation of HIF-2alpha protein,
      often by inactivation of the E3 ligase VHL (von Hippel-Lindau). Herein we
      disclose our structure based drug design (SBDD) approach that culminated in the
      identification of PT2385, the first HIF-2alpha antagonist to enter clinical
      trials. Highlights include the use of a putative n -> pi*Ar interaction to guide
      early analog design, the conformational restriction of an essential hydroxyl
      moiety, and the remarkable impact of fluorination near the hydroxyl group.
      Evaluation of select compounds from two structural classes in a sequence of
      PK/PD, efficacy, PK, and metabolite profiling identified 10i (PT2385, luciferase
      EC50 = 27 nM) as the clinical candidate. Finally, a retrospective
      crystallographic analysis describes the structural perturbations necessary for
      efficient antagonism.

PMID- 30289717
TI  - Long-Lasting Complex Reaction Behavior in a Closed Ferroin-Bromate
      Hydroxybenzenesulfonate System.
AB  - The bromate-phenolsulfonate reaction was found to exhibit spontaneous
      oscillations in a batch reactor, where the addition of small amounts of ferroin
      would result in nonoscillatory behavior. As the ferroin concentration was
      increased, the system produced very rich nonlinear behavior, including three
      isolated oscillatory regimes that were separated by as long as 48 h
      nonoscillatory period. The long-lasting nonlinear behavior may be attributed to
      the slow desulfonation of phenolsulfonate in an acidic solution, forming phenol
      like intermediates. However, unlike the bromate-phenol oscillator, oxygen was
      found to greatly influence the reaction, and various complex oscillations could
      be observed by tuning the oxygen concentration. Mechanistic studies performed
      through employing 1H NMR spectroscopy and mass spectrometry to measure
      intermediate species at different stages of the reaction were able to identify
      1,4-benzoquinone, 2-bromo-1,4-benzoquinone, 2,6-dibromo-1,4-benzoquinone, and
      2,4,6-tribromophenol as major components during the reaction.

PMID- 30289718
TI  - Relevance of the Resonance Junctions on the Arnold Web to Dynamical Tunneling and
      Eigenstate Delocalization.
AB  - We study the competition and correspondence between the classical and quantum
      routes to intramolecular vibrational energy redistribution (IVR) in a three
      degrees of freedom model effective Hamiltonian. Specifically, we focus on the
      classical and the quantum dynamics near the resonance junctions on the Arnold web
      that are formed by an intersection of independent resonances. The regime of
      interest models the IVR dynamics from highly excited initial states near
      dissociation thresholds of molecular systems wherein both classical and purely
      quantum, involving dynamical tunneling, routes to IVR coexist. In the vicinity of
      a resonance junction, classical chaos is inevitably present, and hence one
      expects the quantum IVR pathways to have a strong classical component as well. We
      show that with increasing resonant coupling strengths the classical component of
      IVR leads to a transition from coherent dynamical tunneling to incoherent
      dynamical tunneling. Furthermore, we establish that the quantum IVR dynamics can
      be predicted based on the structures on the classical Arnold web. In addition, we
      investigate the nature of the highly excited eigenstates to identify the quantum
      signatures of the multiplicity-2 junctions. For the parameter regimes studies
      herein, by projecting the eigenstates onto the Arnold web, we find that
      eigenstates in the vicinity of the junctions are primarily delocalized due to
      dynamical tunneling.

PMID- 30289719
TI  - Discovery of a Branched Peptide That Recognizes the Rev Response Element (RRE)
      RNA and Blocks HIV-1 Replication.
AB  - We synthesized and screened a unique 46 656-member library composed of unnatural
      amino acids that revealed several hits against RRE IIB RNA. Among the hit
      peptides identified, peptide 4A5 was found to be selective against competitor
      RNAs and inhibited HIV-1 Rev-RRE RNA interaction in cell culture in a p24 ELISA
      assay. Biophysical characterization in a ribonuclease protection assay suggested
      that 4A5 bound to the stem-loop region in RRE IIB while SHAPE MaP probing with
      234 nt RRE RNA indicated additional interaction with secondary Rev binding sites.
      Taken together, our investigation suggests that HIV replication is inhibited by
      4A5 blocking binding of Rev and subsequent multimerization.

PMID- 30289720
TI  - Catalytic Asymmetric [4 + 3] Annulation of C, N-Cyclic Azomethine Imines with
      Copper Allenylidenes.
AB  - The first asymmetric decarboxylative [4 + 3] annulation of propargylic carbamates
      with C, N-cyclic azomethine imines has been developed successfully by a copper- N
      heterocyclic carbine system. This strategy led to a series of optically active
      isoquinoline-fused triazepine derivatives in good yields and with excellent
      enantio- and diastereoselectivities. Remarkably, Cu-allenylidene intermediates
      play a crucial role in this transformation.

PMID- 30289721
TI  - Design, Synthesis, and Pharmacological Evaluation of Novel beta2/3 Subunit
      Selective gamma-Aminobutyric Acid Type A (GABAA) Receptor Modulators.
AB  - Subunit-selective modulation of gamma-aminobutyric acid type A receptors (GABAAR)
      is considered to exert fewer side effects compared to unselective clinically used
      drugs. Here, the beta2/3 subunit-selective GABAAR modulators valerenic acid (VA)
      and loreclezole (LOR) guided the synthesis of novel subunit-selective ligands
      with simplified structures. We studied their effects on GABAARs expressed in
      Xenopus laevis oocytes using two-microelectrode voltage clamp technique. Five
      compounds showed significantly more efficacious modulation of GABA-evoked
      currents than VA and LOR with retained potency and selectivity. Compound 18 [( E)
      2-Cyano-3-(2,4-dichlorophenyl)but-2-enamide] induced the highest maximal
      modulation of GABA-induced chloride currents ( Emax: 3114 +/- 242%), while 12 [(
      Z)-3-(2,4-dichlorophenyl)but-2-enenitrile] displayed the highest potency (EC50:
      13 +/- 2 MUM). Furthermore, in hippocampal neurons 12 facilitated phasic and
      tonic GABAergic inhibition, and in vivo studies revealed significantly more
      potent protection against pentylenetetrazole (PTZ)-induced seizures compared to
      VA and LOR. Collectively, compound 12 constitutes a novel, simplified, and
      subunit-selective GABAAR modulator with low-dose anticonvulsant activity.

PMID- 30289723
TI  - Sequential Prodrug Strategy To Target and Eliminate ACPA-Selective Autoreactive B
      Cells.
AB  - Autoreactive B cells are thought to play a pivotal role in many autoimmune
      diseases. Rheumatoid arthritis (RA) is an autoimmune disease affecting ~1% of the
      Western population and is hallmarked by the presence of anticitrullinated
      proteins antibodies (ACPA) produced by autoreactive B cells. We intend to develop
      a method to target and selectively eliminate these autoreactive B cells using a
      sequential antigen prodrug targeting strategy. As ACPA-expressing B cells are
      thought to play essential roles in RA-disease pathogenesis, we used this B cell
      response as a prototype to analyze the feasibility to generate a construct
      consisting of a biologically silenced, that is, blocked, antigen connected to a
      cytotoxic prodrug. Blocking of the antigen is considered relevant as it is
      anticipated that circulating autoantibodies will otherwise clear the antigen
      prodrug before it can reach the target cell. The antigen-prodrug can only bind to
      the autoantigen-specific B cell receptor (BCR) upon enzymatic removal of the
      blocking group in close proximity of the B cell surface. BCR binding ultimately
      induces antigen-specific cytotoxicity after internalization of the antigen. We
      have synthesized a cyclic citrullinated peptide (CCP) antigen suitable for BCR
      binding and demonstrated that binding by ACPA was impaired upon introduction of a
      carboxy- p-nitrobenzyl (CNBz) blocking group at the side chain of the citrulline
      residue. Enzymatic removal of the CNBz moiety by nitroreductase fully restored
      citrulline-specific recognition by both ACPA and ACPA-expressing B cells and
      showed targeted cell death of CCP-recognizing B cells only. These results mark an
      important step toward antigen-specific B cell targeting in general and more
      specifically in RA, as successful blocking and activation of citrullinated
      antigens forms the basis for subsequent use of such construct as a prodrug in the
      context of autoimmune diseases.

PMID- 30289722
TI  - Predicting the Binding of Fatty Acid Amide Hydrolase Inhibitors by Free Energy
      Perturbation.
AB  - Since a goal of most drug discovery projects in either academia or industry is to
      design molecules that selectively bind to the desired protein, determination of
      protein-ligand binding free energies is of utmost importance in computer aided
      drug design. With the help of significant improvements in computer power,
      enhanced sampling techniques and accuracy of force fields, FEP (free energy
      perturbation) is becoming an important tool to estimate binding free energies in
      many drug discovery projects both retrospectively and prospectively. We have
      evaluated the ability of Schrodinger's FEP+ to predict relative binding free
      energies of a congeneric series of noncovalent fatty acid amide hydrolase (FAAH)
      inhibitors using an in-house crystal structure. This study shows that although an
      impressively accurate correlation can be obtained with experimental IC50s
      considering small perturbations on the deeper side of the pocket, the same was
      not observed with small perturbations on the relatively more open-ended and
      solvent-accessible side of the pocket. To understand these observations, we
      thoroughly investigated several key factors including the sampling of
      asymmetrically substituted rings, different perturbation maps, impact of
      simultaneous perturbations at two different ends of the ligand, and selecting the
      perturbations in a "chemically sensible" way.

PMID- 30289724
TI  - UV-Responsive Behavior of Multistate and Multiscale Self-Assemblies Constructed
      by Gemini Surfactant 12-3-12.2Br- and trans- o-Methoxy-cinnamate.
AB  - Photoresponsive systems with adjustable self-assembly morphologies and tunable
      rheological properties have aroused widespread concern of researchers in recent
      years because of their prospect applications in controlled release,
      microfluidics, sensors, and so forth. In this paper, we combine a cationic Gemini
      surfactant 12-3-12.2Br- and trans-2-methoxy-cinnamate ( trans-OMCA) together to
      create a representative UV-responsive self-assembly system. The system displays
      abundant self-assembly behaviors, and the self-assemblies with different states
      and different scales including wormlike micelles, vesicles, and lyotropic liquid
      crystals (LCs) as well as an aqueous two-phase system (ATPS) are observed even at
      lower surfactant concentration. The UV-responsive behavior of the formed self
      assemblies is investigated systematically. The results have shown that the
      photoisomerization of OMCA from trans form to cis form under UV light irradiation
      alters the hydrophobicity and steric hindrance effect of OMCA and thus affects
      the molecular packing at the micellar interface and further leads to the
      transformation of assembly morphologies. The long wormlike micelles can gradually
      transform into much shorter rodlike micelles under UV irradiation and companied
      by the decrease of solution viscosity by 2 orders of magnitude. In addition, the
      vesicles can evolve into multistate self-assembly structures including the ATPS,
      wormlike micelles, rod-like micelles, and small spherical micelles depending on
      the UV irradiation time. The ATPS and its adjacent anisotropic LC phase can
      respectively combine into a single phase and separate into ATPS under UV
      irradiation. The morphologies of assemblies in the 12-3-12.2Br-/ trans-OMCA mixed
      system can be tailored by adjusting the system composition and duration of UV
      light irradiation on purpose. The photoresponsive system with abundant self
      assembly behaviors and tunable rheological properties has wide application
      prospect in numerous fields such as drug delivery, materials science, smart
      fluids, and so forth, and the macroscopic phase separation and combination
      provide novel strategies for effective separation and purification of certain
      substances.

PMID- 30289725
TI  - Synthesis and Property of Copper-Impregnated alpha-MnO2 Semiconductor Quantum
      Dots.
AB  - Because of the superior optical and electrical properties, copper-impregnated
      size tuneable high-temperature stable manganese dioxide semiconductor quantum
      dots (SQDs) have been successfully synthesized by a modified chemical synthesis
      technique. Their size-dependent dielectric properties, semiconducting properties,
      and current-voltage ( I- V) characteristics have been investigated. X-ray
      diffraction pattern and Raman spectra confirmed that the required phase is
      present. Because of the different sintering temperature tuneable size of SQDs has
      been found and confirmed by high-resolution transmission electron microscopy. The
      band gap energy of the material is found to be 1.25-1.67 eV, measured from Tauc
      plot using UV-vis absorbance spectrum and their semiconducting properties have
      been confirmed by the non linear current-voltage ( I- V) behavior. Most intense
      green emission peak of photoluminescence (PL) spectroscopy confirms the oxygen
      vacancy defect state. The stoke shifting of Raman spectra, UV absorption, and PL
      emission are the footprint of quantum confinement effect. Incorporation of a
      little amount of Cu in tetragonal hollandite structure of alpha-MnO2 generates
      strain within that structure. This leads to create sufficient crystal defect
      state as well as rise in dielectric constant accompanied with low dielectric loss
      and higher ac conductivity. All these highly desirable properties make the SQDs a
      potential candidate for developing multifunctional photo-electronic devices.
      Owing to the tuneable band gap and electronic transport of the SQDs, we realized
      that the controllable size paves the way for designing SQDs possessing unique
      properties for optical and electronic device applications. Using this material as
      a high dielectric separator, a high-performance supercapacitor has been
      successfully fabricated which can light up 15 light-emitting diodes for 47 min 23
      s after charging them only for 30 s.

PMID- 30289726
TI  - Scalable Microfluidic Platform for Flexible Configuration of and Experiments with
      Microtissue Multiorgan Models.
AB  - Microphysiological systems hold the promise to increase the predictive and
      translational power of in vitro substance testing owing to their faithful
      recapitulation of human physiology. However, the implementation of academic
      developments in industrial settings remains challenging. We present an injection
      molded microfluidic microtissue (MT) culture chip that features two channels with
      10 MT compartments each and that was designed in compliance with microtiter plate
      standard formats. Polystyrene as a chip material enables reliable, large-scale
      production and precise control over experimental conditions due to low adsorption
      or absorption of small, hydrophobic molecules at or into the plastic material in
      comparison with predecessor chips made of polydimethylsiloxane. The chip is
      operated by tilting, which actuates gravity-driven flow between reservoirs at
      both ends of every channel, so that the system does not require external tubing
      or pumps. The flow rate can be modulated by adjusting the tilting angle on
      demand. The top-open design of the MT compartment enables efficient MT loading
      using standard or advanced pipetting equipment, ensures oxygen availability in
      the chip, and allows for high-resolution imaging. Every channel can be loaded
      with up to 10 identical or different MTs, as demonstrated by culturing liver and
      tumor MTs in the same medium channel on the chip.

PMID- 30289727
TI  - The Influence of Temperature on Embryonic Respiration, Growth, and Sex
      Determination in a Western Australian Population of Green Turtles (Chelonia
      mydas).
AB  - The thermal environment of sea turtle embryos has marked effects on many aspects
      of their development and energetics and has consequences for posthatching stages.
      Here we incubated Chelonia mydas embryos from Ningaloo Reef in Western Australia
      at a range of temperatures (27 degrees , 29 degrees , 30 degrees , 31 degrees ,
      32 degrees , and 30 degrees  +/- 5 degrees C) to determine development rates and
      the pivotal temperature for sex determination. We also measured embryonic growth,
      oxygen consumption, and carbon dioxide production throughout development at 27
      degrees  and 31 degrees C. Metabolic rates were higher at 31 degrees C than at 27
      degrees C, but total energy expenditure was greater at 27 degrees C, with 2,281
      mL of oxygen consumed compared with 1,992 mL at 31 degrees C. Respiration at both
      temperatures showed a pattern typical of sea turtle embryos, with peak rates
      occurring at approximately 85% of development and then declining toward hatching.
      Hatchlings produced at higher incubation temperatures developed faster, were
      smaller, and had larger residual yolk masses than hatchlings produced at lower
      temperatures. The pivotal temperature that produced an equal sex ratio was 29.2
      degrees C, with mixed sexes produced between 27.9 degrees  and 30.4 degrees C.
      Our results showed that the Ningaloo population of C. mydas has somewhat
      different thermal sensitivities than other C. mydas populations and justified why
      is it necessary to collect population-specific data to accurately project the
      impacts of global warming on focal populations.

PMID- 30289728
TI  - Pharmacotherapeutic management of comorbid polycystic ovary syndrome and
      diabetes.
AB  - INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in
      premenopausal women. Insulin resistance and glucose intolerance are very
      prevalent metabolic complications in women with PCOS, especially in those
      presenting with weight excess. Therapeutic strategies targeting insulin
      resistance in PCOS are of interest because of their overall safety and their
      beneficial effects on metabolic and reproductive features. Areas covered: The
      authors review systematically all of the available therapeutic interventions
      targeting insulin resistance and/or disturbances of glucose metabolism in women
      with PCOS. Expert opinion: The diagnosis of glucose tolerance disorders in women
      with PCOS requires an oral glucose tolerance test. Strategies addressing weight
      excess and abdominal adiposity, from lifestyle modification to insulin
      sensitizers, may improve insulin resistance and glucose tolerance in women with
      PCOS. However, amelioration of signs and symptoms of PCOS usually requires the
      loss of large amounts of weight for it to be noticeable. Bariatric surgery has
      emerged as the most successful approach for obese patients with PCOS, because
      glucose intolerance, diabetes, and PCOS resolve in most cases through follow-ups.
      At present, the role of novel drugs targeting insulin resistance and/or diabetes
      such as inositols, berberine, resveratrol, and incretin-based therapies are yet
      to be properly established.

PMID- 30289729
TI  - Mutation Profiles in Glioblastoma 3D Oncospheres Modulate Drug Efficacy.
AB  - Glioblastoma (GBM) is a lethal brain cancer with a median survival time of
      approximately 15 months following treatment. Common in vitro GBM models for drug
      screening are adherent and do not recapitulate the features of human GBM in vivo.
      Here we report the genomic characterization of nine patient-derived, spheroid GBM
      cell lines that recapitulate human GBM characteristics in orthotopic xenograft
      models. Genomic sequencing revealed that the spheroid lines contain alterations
      in GBM driver genes such as PTEN, CDKN2A, and NF1. Two spheroid cell lines, JHH
      136 and JHH-520, were utilized in a high-throughput drug screen for cell
      viability using a 1912-member compound library. Drug mechanisms that were
      cytotoxic in both cell lines were Hsp90 and proteasome inhibitors. JHH-136 was
      uniquely sensitive to topoisomerase 1 inhibitors, while JHH-520 was uniquely
      sensitive to Mek inhibitors. Drug combination screening revealed that PI3 kinase
      inhibitors combined with Mek or proteasome inhibitors were synergistic. However,
      animal studies to test these drug combinations in vivo revealed that Mek
      inhibition alone was superior to the combination treatments. These data show that
      these GBM spheroid lines are amenable to high-throughput drug screening and that
      this dataset may deliver promising therapeutic leads for future GBM preclinical
      studies.

PMID- 30289730
TI  - Pharmacotherapy for the prevention of malaria in pregnant women: currently
      available drugs and challenges.
AB  - INTRODUCTION: Malaria in pregnancy continues to be a significant public health
      burden globally, with over 100 million women at risk each year. Sulfadoxine
      pyrimethamine (SP) is the only antimalarial recommended for intermittent
      preventive therapy in pregnancy (IPTp) but increasing parasite resistance
      threatens its viability. There are few other available antimalarial therapies
      that currently have sufficient evidence of tolerability, safety, and efficacy to
      replace SP. Areas covered: Novel antimalarial combinations are under
      investigation for potential use as chemoprophylaxis and in IPTp regimens. The
      present review summarizes currently available therapies, emerging candidate
      combination therapies, and the potential challenges to integrating these into
      mainstream policy. Expert opinion: Alternative drugs or combination therapies to
      SP for IPTp are desperately required. Dihydroartemisinin-piperaquine and
      azithromycin-based combinations are showing great promise as potential candidates
      for IPTp but pharmacokinetic data suggest that dose modification may be required
      to ensure adequate prophylactic efficacy. If a suitable candidate regimen is not
      identified in the near future, the success of chemopreventive strategies such as
      IPTp may be in jeopardy.

PMID- 30289731
TI  - Is Ovarian Tissue Cryopreservation and Transplantation Still Experimental? It Is
      a Matter of Female Age and Type of Cancer.

PMID- 30289733
TI  - Reply to M. von Wolff et al.

PMID- 30289732
TI  - Adjuvant Gemcitabine Plus Docetaxel Followed by Doxorubicin Versus Observation
      for High-Grade Uterine Leiomyosarcoma: A Phase III NRG Oncology/Gynecologic
      Oncology Group Study.
AB  - PURPOSE: We conducted a randomized phase III trial to determine whether adjuvant
      chemotherapy improves survival in women with uterine leiomyosarcoma. METHODS:
      Women with uterus-confined, high-grade leiomyosarcoma who were confirmed disease
      free by imaging were randomly assigned to four cycles of gemcitabine plus
      docetaxel, followed by four cycles of doxorubicin, or to observation. All were
      followed for evidence of recurrence. The primary end point was overall survival
      (OS). RESULTS: With international collaboration, 38 of the targeted accrual of
      216 patients were enrolled, after which the study was closed by the National
      Cancer Institute for accrual futility. Twenty patients were assigned to
      chemotherapy, 18 to observation. Among the 17 patients treated with at least one
      cycle of chemotherapy, grade 3 or 4 toxicities were observed in 47%; among the 18
      patients assigned to observation, one had grade 3 hypertension. There were six
      deaths (chemotherapy, n = 5; observation, n = 1), all due to disease. The
      restricted mean survival time for OS was estimated as 34.3 months (95% CI, 25.3
      to 43.3 months) in the chemotherapy arm and as 46.4 months (95% CI, 43.6 to 49.1
      months) in the observation arm. There were eight recurrences in each arm. The
      restricted mean survival time for recurrence-free survival was estimated as 18.1
      (95% CI, 14.2 to 22.0) months in the chemotherapy arm and as 14.6 months (95% CI,
      10.3 to 19.0 months) in the observation arm. Neither survival outcome comparison
      was considered statistically robust, due to the small sample size. CONCLUSION:
      Despite international collaboration to test the role of adjuvant chemotherapy in
      uterine-confined leiomyosarcoma, this study was closed for accrual futility.
      Although the sample size precludes robust statistical comparison, observed OS and
      recurrence-free survival data do not show superior outcomes with adjuvant
      chemotherapy.

PMID- 30289734
TI  - IgG4-related Cardiovascular Disease from the Aorta to the Coronary Arteries:
      Multidetector CT and PET/CT.
AB  - Immunoglobulin G4 (IgG4)-related disease can affect the cardiovascular system,
      including the coronary arteries and pericardium and especially the walls of large
      and medium-sized vessels. The presence of coronary involvement is critical, as
      this condition can cause myocardial ischemia or sudden cardiac death. Although
      histopathologic examination remains the reference standard for detecting organ
      involvement and diagnosing IgG4-related disease, obtaining biopsy or surgical
      specimens from the vessel wall is still challenging. Because patients may be only
      mildly symptomatic, noninvasive imaging evaluation of IgG4-related cardiovascular
      disease (CVD) has an essential role in not only the diagnosis but also the
      management of this condition. Multidetector CT is a useful noninvasive
      examination for establishing the primary diagnosis and defining anatomic
      landmarks and their relationships. The spectrum of vessel involvement is vast,
      with varied manifestations. Radiologists should be familiar with inflammatory
      vasculitis, aneurysmal change, and pseudotumor formation in all vessels and the
      distribution of these conditions throughout the body. Electrocardiographically
      gated CT enables accurate, fast, and noninvasive characterization of coronary
      pathologic conditions and thus has an important advantage over catheter
      angiography. Combined PET/CT can depict inflammatory processes and help
      distinguish IgG4-related CVD from atherosclerosis. Familiarity with the PET/CT
      and CT findings of inflammatory processes involved in IgG4-related CVD is
      important for accurate diagnosis and evaluation of therapeutic response during
      follow-up. The multidetector CT and PET/CT characteristics of IgG4-related CVD,
      such as aortitis, periaortitis, arteritis, and periarteritis and including
      coronary artery involvement and pericarditis, are reviewed. In addition, the
      inflammatory process, quantification of active inflammation, and therapeutic
      response during follow-up associated with IgG4-related CVD are described. Online
      DICOM image stacks are available for this article. (c)RSNA, 2018.

PMID- 30289735
TI  - LI-RADS Version 2018 Ancillary Features at MRI.
AB  - The Liver Imaging Reporting and Data System (LI-RADS) standardizes performance of
      liver imaging in patients at risk for hepatocellular carcinoma (HCC) as well as
      interpretation and reporting of the results. Developed by experts in liver
      imaging and supported by the American College of Radiology, LI-RADS assigns to
      observations categories that reflect the relative probability of benignity, HCC,
      or other malignancy. While category assignment is based mainly on major imaging
      features, ancillary features may be applied to improve detection and
      characterization, increase confidence, or adjust LI-RADS categories. Ancillary
      features are classified as favoring malignancy in general, HCC in particular, or
      benignity. Those favoring malignancy in general or HCC in particular may be used
      to upgrade by a maximum of one category up to LR-4; those favoring benignity may
      be used to downgrade by a maximum of one category. If there are conflicting
      ancillary features (ie, one or more favoring malignancy and one or more favoring
      benignity), the category should not be adjusted. Ancillary features may be seen
      at diagnostic CT, MRI performed with extracellular agents, or MRI performed with
      hepatobiliary agents, with the exception of one ancillary feature assessed at US.
      This article focuses on LI-RADS version 2018 ancillary features seen at MRI.
      Specific topics include rules for ancillary feature application; definitions,
      rationale, and illustrations with clinical MRI examples; summary of evidence and
      diagnostic performance; pitfalls; and future directions. (c)RSNA, 2018.

PMID- 30289736
TI  - Examination of Health System Resources and Costs Associated With Transitioning
      Cancer Survivors to Primary Care: A Propensity-Score-Matched Cohort Study.
AB  - BACKGROUND:: Transitioning low-risk cancer survivors back to their primary care
      provider (PCP) has been shown to be safe but the effect on health system
      resources and costs has not been examined. METHODS:: A Well Follow-Up Care
      Initiative (WFCI) was implemented in the publicly funded health system. Low-risk
      breast cancer (BC) survivors in the WFCI intervention group were transitioned
      from oncologist-led cancer clinics to PCPs. We compared health system costs
      ($2,014 in Canadian dollars) and resource utilization in this intervention group
      with that in propensity-score-matched nontransitioned BC survivors (ie, controls)
      diagnosed in the same year, with similar disease profile and patient
      characteristics using publicly funded administrative databases. RESULTS:: A total
      of 2,324 BC survivors from the WFCI intervention group were 1:1 matched to
      controls and observed for 25 months. Compared with controls, survivors in the
      intervention group incurred a similar number of PCP visits (6.9 v 7.5) and fewer
      oncologist visits (0.3 v 1.2) per person-year. Fewer survivors in the
      intervention group (20.1%) were hospitalized than in the control group (24.4%).
      There were no differences in emergency visits. More survivors in the intervention
      group had mammograms (82.6% v 73.1%), but other diagnostic tests were less
      frequent. There was a 39.3% reduction in overall mean annual costs ($6,575 v
      $10,832) and a 22.1% reduction in overall median annual costs ($2,261 v $2,903).
      Overall survival in the intervention group was not worse than controls.
      CONCLUSION:: Transitioning low-risk BC survivors to PCPs was associated with
      lower health system resource use and a lower annual cost per patient than matched
      controls. The WFCI model represents a reasonable approach at the population level
      to delivering quality care for low-risk BC survivors that seems to be cost
      effective.

PMID- 30289737
TI  - Returning Results to Family Members: Professional Duties in Genomics Research in
      the United States.
AB  - This article critically appraises the ethical and legal duties to disclose
      findings to the family members of research participants. These family members
      stand to benefit in important ways from discoveries that can inform their own
      health and reproductive risks. However, careful appreciation of how medical
      research differs from clinical practice and of the uncertainties at stake in
      genomic research complicates any warning to relatives. Research laboratories
      should generally be immune from liability for failing to diagnose or disclose a
      genetic disorder in time to prevent adverse outcomes for a participant's family
      members or to return properly interpreted test results for even direct findings
      under investigation, let alone incidental ones. The only exception is where
      warning relatives of medical risks is very likely to prevent imminent harm and
      would not override known participant wishes. Genomic autopsy studies for sudden
      death satisfy these conditions of life-saving potential for relatives without
      disrespect to subjects. These are among the rare instances in which we conclude
      that offering results to family members is not just permissible but obligatory,
      not just as a moral matter but as a legal one.

PMID- 30289738
TI  - Founders Series Interview with Dr. Dorothy Racinski-Gregory.

PMID- 30289740
TI  - If It's Not Broken, Don't Fix It: A Call to Amend the Definitions Provided by the
      Food and Drug Administration to Include the Newly Developed Meal-Kit Delivery
      Industry.

PMID- 30289739
TI  - Trouble in Mind: Healthcare Informed Consent, Surgery, Anesthesia, and the Aging
      Brain.

PMID- 30289741
TI  - Ransomware: The Virus Attacking the Healthcare Industry.

PMID- 30289742
TI  - Supplement Regulation for Sports Nutrition Supplements.

PMID- 30289744
TI  - Pediatric Sports Specialization in Elite Ice Hockey Players.
AB  - BACKGROUND: Pediatric sports specialization, defined as intense year-round
      training in a single sport as a result of excluding other sports for more than 8
      months per year, is common in the United States. There are demonstrated physical
      and social risks to early pediatric sports specialization (defined as before age
      12 years). While thought to be needed to acquire appropriate experience and excel
      in a given sport, there remains little information on when athletes at the
      highest levels of their sport specialized. This study aimed to define when
      professional and collegiate ice hockey players specialized. HYPOTHESIS: Early
      sports specialization before age 12 years will not be common among elite-level
      (professional and collegiate) ice hockey players. STUDY DESIGN: Retrospective
      cross-sectional survey study. LEVEL OF EVIDENCE: Level 3. METHODS: Male
      professional and collegiate ice hockey players within 1 National Hockey League
      organization and 2 National Collegiate Athletic Association (NCAA) organizations
      who were 18 years of age or older completed a survey at training camp detailing
      their history of sports participation and specialization. RESULTS: A total of 91
      athletes participated in the study (mean age, 22.8 years; range, 18-39 years).
      The mean age at the start of any sports participation was 4.5 years, and the mean
      age of sports specialization was 14.3 years. The mean age of specialization in
      the professional group, the NCAA Division I group, and the NCAA Division III
      group was 14.1, 14.5, and 14.6 years, respectively. CONCLUSION: Early pediatric
      sports specialization is not common in elite-level (professional and collegiate)
      ice hockey players. CLINICAL RELEVANCE: Early pediatric sports specialization
      before age 12 years is not necessary for athletic success in professional and
      collegiate ice hockey. This study provides further evidence supporting the
      recommendations of the American Medical Society for Sports Medicine, American
      Academy of Pediatrics, and American Orthopaedic Society for Sports Medicine
      against early sports specialization.

PMID- 30289743
TI  - NRG1 PLGA MP locally induce macrophage polarisation toward a regenerative
      phenotype in the heart after acute myocardial infarction.
AB  - Neuregulin-1 loaded poly(lactic-co-glycolic acid) (PLGA) microparticles hold
      great promise for treating acute myocardial infarction, as they have been proved
      to recover heart function and induce positive heart remodelling in preclinical
      studies. More recently, the inflammatory response of the heart after acute
      myocardial infarction (AMI) has been identified as one of the major mechanisms in
      cardiac tissue remodelling and repair. However, the connection between neuregulin
      1 PLGA microparticles and inflammation is still not well characterised. In the
      present study we assessed this relationship in a mouse AMI model. First, in vitro
      evidence indicated that neuregulin-1 PLGA microparticles induced a macrophage
      polarisation toward a regenerative phenotype (CD206+ cells), preventing
      macrophages from evolving toward the inflammatory phenotype (B7-2+ cells). This
      correlated with in vivo experiments, where neuregulin-1 PLGA microparticles
      locally improved the CD206+/B7-2+ ratio. Moreover, neuregulin-1 PLGA
      microparticles were administered at different time points (15 min, 24, 72 and 168
      h) after infarction induction without causing secondary inflammatory issues. The
      time of treatment administration did not alter the inflammatory response. Taken
      together, these results suggest that neuregulin-1 PLGA microparticles can be
      administered depending on the therapeutic window of the encapsulated drug and
      that they enhance the heart's reparative inflammatory response after acute
      myocardial infarction, helping cardiac tissue repair.

PMID- 30289745
TI  - Proteome and transcriptome profiling of equine myofibrillar myopathy identifies
      diminished peroxiredoxin 6 and altered cysteine metabolic pathways.
AB  - Equine myofibrillar myopathy (MFM) causes exertional muscle pain and is
      characterized by myofibrillar disarray and ectopic desmin aggregates of unknown
      origin. To investigate the pathophysiology of MFM, we compared resting and 3 h
      post-exercise transcriptomes of gluteal muscle and the resting skeletal muscle
      proteome of MFM and control Arabian horses using RNA-sequencing and iTRAQ
      analyses. Three hours after exercise, 191 genes were identified as differentially
      expressed (DE) in MFM vs. control muscle with > 1 log2 fold change [FC] in genes
      involved in sulfur compound/ cysteine metabolism such as cystathionine-beta
      synthase [CBS, ?4.51], a cysteine and neutral amino acid membrane transporter
      [SLC7A10, ?1.80 MFM] and a cationic transporter [SLC24A1, ?1.11 MFM). In MFM vs.
      control at rest, 284 genes were DE with > 1 log2 FC in pathways for structure
      morphogenesis, fiber organization, tissue development and cell differentiation
      including> 1 log2 FC in cardiac alpha actin [ACTC1 ?2.5 MFM], cytoskeletal
      desmoplakin [DSP ?2.4 MFM] and basement membrane usherin [USH2A ?2.9 MFM].
      Proteome analysis revealed significantly lower antioxidant peroxiredoxin 6
      content (PRDX6, ?4.14 log2 FC MFM), higher fatty acid transport enzyme carnitine
      palmitoyl transferase (CPT1B, ?3.49 MFM) and lower sarcomere protein tropomyosin
      (TPM2, ?3.24 MFM) in MFM vs. control muscle at rest. We propose that in MFM
      horses, altered cysteine metabolism and a deficiency of cysteine-containing
      antioxidants combined with a high capacity to oxidize fatty acids and generate
      ROS during aerobic exercise causes chronic oxidation and aggregation of key
      proteins such as desmin.

PMID- 30289746
TI  - Identifying SNPs and candidate genes for three litter traits using single-step
      GWAS across six parities in Landrace and Large White pigs.
AB  - Total number born(TNB),number born alive(NBA)and litter weight born alive(LWB)are
      critically important traits in pig production.The sow's parity is one of the
      major factors influencing litter traits.Because of monogenic or polygenic
      contributions and the presence of temporal gene effects in different sows'
      parities,it is difficult to clarify the biological and genetic background.To
      systematically explore the genetic mechanism of litter traits,18 GWASs were
      conducted using single-step GWAS(ssGWAS) based on two breeds(908 Landrace and
      1130 Large White sow litter records)for each litter trait in different parities.A
      total of 300 Landrace and 300 Large White sows were genotyped by
      sequencing(GBS).ssGWAS was performed separately for each breed and each parity
      due to population stratification and temporal gene effect.In summary,we
      identified 80(15 for Landrace and 65 for Large White),227(52 for Landrace,175 for
      Large White),and 187(34 for Landrace,153 for Large White) SNPs affecting TNB,NBA
      and LWB respectively.Of them,we suggested that a total of 22 loci were shared by
      TNB,NBA and LWB.These results indicated the existence of gene temporal effect in
      each parity.Furthermore,our findings suggested four interesting candidate genes
      (FBXL7,ALDH1A2,LEPR and DDX1)associated with litter traits in different parities
      that have a major effect on embryonic development progression.In conclusion,22
      crucial SNPs and 4 interesting candidate genes were identified for three litter
      traits across six parities.These findings advance our understanding of the
      genetic architecture of litter traits and confirm the presence of temporal gene
      effects in different parities.Importantly, functional validation studies for
      findings of particular interest are recommended in litter traits.

PMID- 30289747
TI  - A Transcriptomic Analysis of the Development of Skeletal Muscle Atrophy in Cancer
      Cachexia in Tumor-Bearing Mice.
AB  - Cancer-Cachexia (CC) is a wasting condition directly responsible for 20-40% of
      cancer-related deaths. The mechanisms controlling development of CC-induced
      muscle wasting are not fully elucidated. Most investigations focus on the post
      cachectic state and do not examine progression of the condition. We recently
      demonstrated mitochondrial degenerations precede muscle wasting in time course
      progression of CC. However, the extent of muscle perturbations prior to wasting
      in CC is unknown. Therefore, we performed global gene expression analysis in CC
      induced muscle wasting to enhance understanding of intramuscular perturbations
      across the development of CC. Lewis Lung Carcinoma (LLC) was injected into the
      hind-flank of C57BL6/J mice at 8 wks age with tumor allowed to develop for 1, 2,
      3, or 4 wks and compared to PBS injected control. Muscle wasting was evident at 4
      wks LLC. RNA sequencing of gastrocnemius muscle samples showed widespread
      alterations in LLC compared to PBS animals with largest differences seen in 4 wk
      LLC suggesting extensive transcriptomic alterations concurrent to muscle wasting.
      Commonly altered pathways included: Mitochondrial Dysfunction and Protein
      Ubiquitination, along with other less studied processes in this condition
      regulating transcription/translation and cytoskeletal structure. Current findings
      present novel evidence of transcriptomic shifts and altered cellular pathways in
      CC-induced muscle wasting.

PMID- 30289748
TI  - Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's
      disease.
AB  - Dietary and supplemental intake of the omega-3 fatty acid docosahexaenoic acid
      (DHA) reduces risk of Alzheimer's disease (AD) and ameliorates symptoms. The
      apolipoprotein E ( APOE) 4 allele is the strongest risk factor for sporadic AD,
      exclusive of age. APOE4 carriers respond well to the DHA present in fish but do
      not respond as well to dietary supplements. The mechanisms behind this varied
      response remain unknown. I posit that the difference is that fish contain DHA in
      phospholipid form, whereas fish oil supplements do not. This influences whether
      DHA is metabolized to nonesterified DHA (free DHA) or a phospholipid form called
      lysophosphatidylcholine DHA (DHA-lysoPC). Free DHA is transported across the
      outer membrane leaflet of the blood-brain barrier (BBB) via passive diffusion,
      and DHA-lysoPC is transported across the inner membrane leaflet of the BBB via
      the major facilitator superfamily domain-containing protein 2A. I propose that
      APOE4 carriers have impaired brain transport of free DHA but not of DHA-lysoPC,
      as a consequence of a breakdown in the outer membrane leaflet of the BBB, putting
      them at increased risk for AD. Dietary sources of DHA in phospholipid form may
      provide a means to increase plasma levels of DHA-lysoPC, thereby decreasing the
      risk of AD.-Patrick, R. P. Role of phosphatidylcholine-DHA in preventing APOE4
      associated Alzheimer's disease.

PMID- 30289749
TI  - Maternal obesity impairs fetal cardiomyocyte contractile function in sheep.
AB  - Obesity is a major public health problem worldwide. In the United States, one
      third of women of reproductive age are obese. Human studies show that maternal
      obesity (MO) predisposes offspring to cardiovascular disease. However, the
      underlying mechanisms remain unclear. Given the similarities between pregnancy in
      sheep and humans, we studied sheep to examine the impact of MO on fetal
      cardiomyocyte contractility at term. We observed that MO impaired cardiomyocyte
      contractility by reducing peak shortening and shortening/relengthening velocity,
      prolonging time to relengthening. MO disrupted Ca2+ homeostasis in fetal
      cardiomyocytes, increasing intracellular Ca2+ and inducing cellular Ca2+
      insensitivity. The Ca2+-release channel was impaired, but Ca2+ uptake was
      unaffected by MO. The upstream kinases that phosphorylate the Ca2+-release
      channel-ryanodine receptor-2, PKA, and calmodulin-dependent protein kinase II
      were activated in MO fetuses. Contractile dysfunction was associated with an
      increased ratio of myosin heavy chain (MHC)-beta to MHC-alpha and upregulated
      cardiac troponin (cTn)-T and tropomyosin, as well as cTn-I phosphorylation. In
      summary, this is the first characterization of the effects of MO on fetal
      cardiomyocyte contractility. Our findings indicate that MO impairs fetal
      cardiomyocyte contractility through altered intracellular Ca2+ handling,
      overloading fetal cardiomyocyte intracellular Ca2+ and aberrant myofilament
      protein composition. These mechanisms may contribute to developmental programming
      by MO of offspring cardiac function and predisposition to later life
      cardiovascular disease in the offspring.-Wang, Q., Zhu, C., Sun, M., Maimaiti,
      R., Ford, S. P., Nathanielsz, P. W., Ren, J., Guo, W. Maternal obesity impairs
      fetal cardiomyocyte contractile function in sheep.

PMID- 30289751
TI  - Small fibers, large impact.

PMID- 30289752
TI  - 2017 ACC/AHA hypertension guidelines: Toward tighter control.

PMID- 30289750
TI  - Deletion in mice of X-linked, Brugada syndrome- and atrial fibrillation
      associated Kcne5 augments ventricular KV currents and predisposes to ventricular
      arrhythmia.
AB  - KCNE5 is an X-linked gene encoding KCNE5, an ancillary subunit to voltage-gated
      potassium (KV) channels. Human KCNE5 mutations are associated with atrial
      fibrillation (AF)- and Brugada syndrome (BrS)-induced cardiac arrhythmias that
      can arise from increased potassium current in cardiomyocytes. Seeking to
      establish underlying molecular mechanisms, we created and studied Kcne5 knockout
      ( Kcne5-/0) mice. Intracardiac ECG revealed that Kcne5 deletion caused
      ventricular premature beats, increased susceptibility to induction of polymorphic
      ventricular tachycardia (60 vs. 24% in Kcne5+/0 mice), and 10% shorter
      ventricular refractory period. Kcne5 deletion increased mean ventricular myocyte
      KV current density in the apex and also in the subpopulation of septal myocytes
      that lack fast transient outward current ( Ito,f). The current increases arose
      from an apex-specific increase in slow transient outward current-1 ( IKslow,1)
      (conducted by KV1.5) and Ito,f (conducted by KV4) and an increase in IKslow,2
      (conducted by KV2.1) in both apex and septum. Kcne5 protein localized to the
      intercalated discs in ventricular myocytes, where Kv2.1 was also detected in both
      Kcne5-/0 and Kcne5+/0 mice. In HL-1 cardiac cells and human embryonic kidney
      cells, KCNE5 and Kv2.1 colocalized at the cell surface, but predominantly in
      intracellular vesicles, suggesting that Kcne5 deletion increases IK,slow2 by
      reducing Kv2.1 intracellular sequestration. The human AF-associated mutation
      KCNE5-L65F negative shifted the voltage dependence of KV2.1-KCNE5 channels,
      increasing their maximum current density >2-fold, whereas BrS-associated KCNE5
      mutations produced more subtle negative shifts in KV2.1 voltage dependence. The
      findings represent the first reported native role for Kcne5 and the first
      demonstrated Kcne regulation of KV2.1 in mouse heart. Increased KV current is a
      manifestation of KCNE5 disruption that is most likely common to both mouse and
      human hearts, providing a plausible mechanistic basis for human KCNE5-linked AF
      and BrS.-David, J-P., Lisewski, U., Crump, S. M., Jepps, T. A., Bocksteins, E.,
      Wilck, N., Lossie, J., Roepke, T. K., Schmitt, N., Abbott, G. W. Deletion in mice
      of X-linked, Brugada syndrome- and atrial fibrillation-associated Kcne5 augments
      ventricular KV currents and predisposes to ventricular arrhythmia.

PMID- 30289753
TI  - Transcatheter aortic valve replacement for bicuspid aortic valve stenosis.

PMID- 30289754
TI  - How long should we follow simple ovarian cysts with pelvic ultrasonography?

PMID- 30289755
TI  - Genitourinary syndrome of menopause in breast cancer survivors:Treatments are
      available.
AB  - When treating the genitourinary syndrome of menopause (GSM) in women with breast
      cancer or at high risk of breast cancer, clinicians must balance the higher
      cancer risks associated with hormonal treatments against the severity of GSM
      symptoms, which can be exacerbated by breast cancer treatments. Options for
      patients who need hormonal therapy include locally applied estrogens,
      dehydroepiandrosterone (DHEA), and estrogen receptor agonists/antagonists, which
      vary in their impact on breast cancer risk.

PMID- 30289756
TI  - Bicuspid aortic valve: Basics and beyond.
AB  - Bicuspid aortic valve, one of the most common congenital cardiac malformations,
      is associated with other valvular abnormalities and aortopathies. It increases
      the risk of thoracic aortic aneurysm and dissection, infective endocarditis, and
      sudden cardiac death. Patients require regular surveillance for progressive
      valvular disease and aortopathy. Although bicuspid aortic valve may occur
      sporadically, many cases are inherited, so first-degree relatives should be
      evaluated and genetic counseling considered.

PMID- 30289757
TI  - Ablation of atrial fibrillation: Facts for the referring physician.
AB  - Radiofrequency ablation has become a safe and effective treatment for atrial
      fibrillation. We believe that referral to an electrophysiologist for
      consideration of ablation may allow for better rhythm control and outcomes by
      altering the natural history of atrial fibrillation progression.

PMID- 30289758
TI  - Office approach to small fiber neuropathy.
AB  - Small fiber neuropathy is often characterized by neuropathic pain in the feet
      with normal nerve conduction studies and neurologic examination. Diagnosis
      requires specialized nerve tests, including autonomic studies and a skin biopsy
      study showing reduced intraepidermal nerve fiber density. Small fiber neuropathy
      has numerous causes but is often idiopathic. A practical approach to identifying
      an underlying cause is to first screen for common ones and then proceed with
      further testing as needed. Treatment consists of correcting the underlying cause,
      managing pain, and modifying lifestyle.

PMID- 30289759
TI  - When stroke runs in the family.

PMID- 30289760
TI  - Pancreatitis: The great masquerader?

PMID- 30289761
TI  - To the Editor: Hypertrophic cardiomyopathy.

PMID- 30289762
TI  - To the Editor: Postsurgical hypoparathyroidism is not primary hypoparathyroidism.

PMID- 30289763
TI  - In reply: Postsurgical hypoparathyroidism is not primary hypoparathyroidism.

PMID- 30289764
TI  - Correction: Liver enzymes.
AB  - In the article by Agganis B, Lee D, Sepe T (Liver enzymes: No trivial elevations,
      even if asymptomatic. Cleve Clin J Med 2018; 85(8):612-617,
      doi:10.3949/ccjm.85a.17103), an error occurred on page 613, in the second
      paragraph in the section about alcohol intake. The words ALT and AST were
      reversed. The paragraph should read as follows: The exact pathogenesis of
      alcoholic hepatitis is incompletely understood, but alcohol is primarily
      metabolized by the liver, and damage likely occurs during metabolism of the
      ingested alcohol. AST elevations tend to be higher than ALT elevations; the
      reason is ascribed to hepatic deficiency of pyridoxal 5'-phosphate, a cofactor of
      the enzymatic activity of ALT, which leads to a lesser increase in ALT than in
      AST. We thank Avinash Alexander, MD, Texas Tech University Health Sciences
      Center, for calling this to our attention. The correction has been made online.

PMID- 30289765
TI  - Operative Management of Abdominal Wound Dehiscence: Outcomes and Factors
      Influencing Time to Healing in Patients Undergoing Surgical Debridement With
      Primary Closure.
AB  - INTRODUCTION: Plastic surgeons are often consulted by other surgical teams for
      management of wound dehiscence following abdominopelvic surgery. OBJECTIVE: The
      purpose of this study is to determine whether operative debridement and primary
      closure of abdominopelvic wounds are safe and expeditious for patients. MATERIALS
      AND METHODS: A retrospective analysis was conducted on a database of patients who
      underwent operative debridement and closure at a single institution between
      January 2011 and December 2015 for dehisced abdominal or pelvic wounds acquired
      from prior obstetric, gynecologic, transplant, plastic, or general surgery
      procedures. RESULTS: Of the 163 patient records identified, 43 patients met
      inclusion criteria. The median time from final debridement and primary surgical
      closure to complete wound healing was 27 days. Time to healing differed
      significantly by index procedure type (P = .004), with obstetric procedures
      requiring the shortest median time (12.0 days) and general surgery procedures
      requiring the longest (39.5 days). Wound healing took 3.6 times longer for
      patients with diabetes (P = .046) and 11.4 times longer for patients who
      experienced delayed superficial wound healing or redehiscence (P = .003).
      Nevertheless, with the exception of 4 patients who died of other causes, all
      wounds (39/39; 100%) achieved complete wound closure. CONCLUSIONS: Operative
      debridement and closure of abdominopelvic wound dehiscence through a
      multidisciplinary team approach with plastic surgery results in expeditious wound
      healing with minimal complications, and it may be safer and more cost effective
      than healing by secondary intention.

PMID- 30289766
TI  - Scaling of resistive random access memory devices beyond 100 nm2: influence of
      grain boundaries studied using scanning tunneling microscopy.
AB  - Resistive Random Access Memory (ReRAM) has emerged as the successor to FLASH in
      memory technology due to its multi-level fabrication possibilities and prospects
      of scaling down virtually to atomic dimensions. However, as we report here, when
      polycrystalline switching materials are used, the ReRAM devices scaled down to
      the sub-5 nm2 area show complete randomness due to inhomogeneous conductance
      values of grains and grain boundaries. By measuring the switching properties of
      grains and grain boundaries individually using a scanning tunneling microscope,
      we demonstrate that the doublet and triplet grain boundaries behave like
      degenerate semiconductors and act as conduction channels that bypass the
      resistive switching of the devices. Fabricating virtual devices using gold
      clusters deposited on top, we show that the random distribution of such highly
      conducting grain boundaries reduces the reliability of nano-scale ReRAM devices
      when scaled down to the sub-10 nm scale.

PMID- 30289767
TI  - Sexual Counseling Provided by Cardiovascular Nurses: Attitudes, Beliefs,
      Perceived Barriers, and Proposed Solutions.
AB  - BACKGROUND: Although sex lives of patients with cardiovascular disease (CVD) are
      affected in various ways and degrees, nurses working with these patients refrain
      from talking about sexual matters with their patients or encounter barriers
      trying to do so. OBJECTIVE: The purpose of this descriptive study was to identify
      attitudes and beliefs of cardiovascular nurses regarding talking to their
      patients about sexual problems, perceived barriers, and proposed solutions.
      METHODS: The sample included 170 nurses working for the cardiology and cardiac
      surgery departments of 1 university hospital, 2 ministry of health hospitals, and
      2 private hospitals in Turkey. Data were collected between April and August 2015
      through a 4-section questionnaire including the Sexual Attitude and Beliefs
      Scale. Descriptive, parametric, and nonparametric statistics were used to analyze
      the data. RESULTS: Most (73.5%) reported not talking to their patients about
      sexual issues, and only 35.9% stated that they had been educated on how to do so.
      The major reason for nurses avoiding discussions about sex with their patients
      was not considering sexuality as a patient care priority (86.4%). Establishing
      privacy for the patient (91.2%) was the solution proposed by most nurses. The
      average score of the nurses on the Sexual Attitude and Beliefs Scale was only
      medium. CONCLUSION: Most of the nurses were untrained about how to talk about
      sexual problems with their patients and therefore were unable to talk about it
      freely.

PMID- 30289768
TI  - Mental health and wellbeing during the transition to fatherhood: a systematic
      review of first time fathers' experiences.
AB  - OBJECTIVE: The aim of this systematic review was to identify and synthesize the
      best available evidence on first time fathers' experiences and needs in relation
      to their mental health and wellbeing during their transition to fatherhood.
      INTRODUCTION: Men's mental health and wellbeing during their transition to
      fatherhood is an important public health issue that is currently under-researched
      from a qualitative perspective and poorly understood. INCLUSION CRITERIA:
      Resident first time fathers (biological and non-biological) of healthy babies
      born with no identified terminal or long-term conditions were included. The
      phenomena of interest were their experiences and needs in relation to mental
      health and wellbeing during their transition to fatherhood, from commencement of
      pregnancy until one year after birth. Studies based on qualitative data,
      including, but not limited to, designs within phenomenology, grounded theory,
      ethnography and action research were included. METHODS: A three-step search
      strategy was used. The search strategy explored published and unpublished
      qualitative studies from 1960 to September 2017. All included studies were
      assessed by two independent reviewers and any disagreements were resolved by
      consensus or with a third reviewer. The recommended Joanna Briggs Institute (JBI)
      approach to critical appraisal, study selection, data extraction and data
      synthesis was used. RESULTS: Twenty-two studies met the eligibility criteria and
      were included in the review, which were then assessed to be of moderate to high
      quality (scores 5-10) based on the JBI Critical Appraisal Checklist for
      Qualitative Research. The studies were published between 1990 and 2017, and all
      used qualitative methodologies to accomplish the overall aim of investigating the
      experiences of expectant or new fathers. Nine studies were from the UK, three
      from Sweden, three from Australia, two from Canada, two from the USA, one from
      Japan, one from Taiwan and one from Singapore. The total number of first time
      fathers included in the studies was 351. One hundred and forty-four findings were
      extracted from the included studies. Of these, 142 supported findings were
      aggregated into 23 categories and seven synthesized findings: 1) New fatherhood
      identity, 2) Competing challenges of new fatherhood, 3) Negative feelings and
      fears, 4) Stress and coping, 5) Lack of support, 6) What new fathers want, and 7)
      Positive aspects of fatherhood. CONCLUSIONS: Based on the synthesized findings,
      three main factors that affect first time fathers' mental health and wellbeing
      during their transition to fatherhood were identified: the formation of the
      fatherhood identity, competing challenges of the new fatherhood role and negative
      feelings and fears relating to it. The role restrictions and changes in lifestyle
      often resulted in feelings of stress, for which fathers used denial or escape
      activities, such as smoking, working longer hours or listening to music, as
      coping techniques. Fathers wanted more guidance and support around the
      preparation for fatherhood, and partner relationship changes. Barriers to
      accessing support included lack of tailored information resources and
      acknowledgment from health professionals. Better preparation for fatherhood, and
      support for couple relationships during the transition to parenthood could
      facilitate better experiences for new fathers, and contribute to better
      adjustments and mental wellbeing in new fathers.

PMID- 30289770
TI  - The Utilization of Interventional Radiologic Procedures in the Surgical
      Management of Placenta Accreta Syndrome.
AB  - The role of Interventional radiologic procedures for the management of suspected
      placenta accreta spectrum (PAS) has evolved considerably over last 3 decades. In
      this article, the authors describe the various techniques of vascular occlusion
      for the management of PAS and provide a brief review of the literature examining
      the pros and cons in the use of these devices.

PMID- 30289769
TI  - Assessing the Feasibility of Providing a Real-Time Response to Seizures Detected
      With Continuous Long-Term Neonatal Electroencephalography Monitoring.
AB  - PURPOSE: Continuous video electroencephalography (cEEG) monitoring is the
      recommended gold standard of care for at-risk neonates but is not available in
      many Neonatal Intensive Care Units (NICUs). To conduct a randomized treatment
      trial of levetiracetam for the first-line treatment of neonatal seizures (the
      NEOLEV2 trial), we developed a monitoring infrastructure at five NICUs,
      implementing recent technological advancements to provide continuous video EEG
      monitoring and real-time response to seizure detection. Here, we report on the
      feasibility of providing this level of care. METHODS: Twenty-five key informant
      interviews were conducted with study neurologists, neonatologists, coordinators,
      and EEG technicians from the commercial EEG monitoring company Corticare. A
      general inductive approach was used to analyze these qualitative data. RESULTS: A
      robust infrastructure for continuous video EEG monitoring, remote review, and
      real-time seizure detection was established at all sites. At the time of this
      survey, 260 babies had been recruited and monitored for 2 to 6 days. The EEG
      technician review by the commercial EEG monitoring company was reassuring to
      families and neonatologists and led to earlier detection of seizures but did not
      reduce work load for neurologists. Neurologists found the automated neonatal
      seizure detector algorithm provided by the EEG software company Persyst useful,
      but the accuracy of the algorithm was not such that it could be used without
      review by human expert. Placement of EEG electrodes to initiate monitoring,
      especially after hours, remains problematic. CONCLUSIONS: Technological
      advancements have made it possible to provide at-risk neonates with continuous
      video EEG monitoring, real-time detection of and response to seizures. However,
      this standard of care remains unfeasible in usual clinical practice. Chief
      obstacles remain starting a recording and resourcing the real-time specialist
      review of suspect seizures.

PMID- 30289771
TI  - Bivalirudin Use During Pulmonary Vein Isolation in a Patient With Heparin-Induced
      Thrombocytopenia.

PMID- 30289772
TI  - Acquired Cutaneous Lymphangiectasia Secondary to Cervical Cancer Treatment.

PMID- 30289773
TI  - Epithelioid Fibrous Histiocytoma: A Concise Review.
AB  - Epithelioid fibrous histiocytoma (EFH) is a rare lesion believed to arise from
      dermal microvascular unit fibroblasts and dendritic histiocytes. EFH has long
      been considered a morphologic variant of benign fibrous histiocytoma
      (dermatofibroma), with prominent epithelioid cytomorphology that can mimic both
      vascular and melanocytic neoplasms. The molecular basis for the relationship
      between EFH and benign fibrous histiocytoma has remained largely unknown, with
      some authors suggesting that EFH represents an entity that is biologically
      distinct from benign fibrous histiocytoma. Recent molecular studies have
      identified the presence of recurrent anaplastic lymphoma kinase (ALK) gene
      rearrangements, a phenomenon that has not been described in benign fibrous
      histiocytoma. These new molecular findings highlight the uniqueness of this rare
      tumor and may prove useful as a diagnostic tool for differentiation from other
      histologic mimics.

PMID- 30289774
TI  - The Delicate Balance: Managing Oxygen Treatment in Neonates.
AB  - This review is based on a Mallinckrodt Pharmaceuticals-sponsored presentation,
      "The Delicate Balance of Managing Oxygen Treatment in Neonates," delivered by Amy
      R Koehn, PhD, NNP-BC, at the National Association of Neonatal Nurses (NANN) 33rd
      Annual Conference, held in Providence, Rhode Island on October 11, 2017. In
      addition to focusing on the potential risks associated with exposing newborn
      tissues to episodes of lower (hypoxic) and higher (hyperoxic) than normal
      concentrations of serum oxygen, the current guidance for target saturation ranges
      and methods of tissue oxygenation measurements in neonates was reviewed. A total
      of 181 neonatal nurses, neonatal nurse practitioners, nurse educators, and nurse
      managers were polled during the presentation using an audience response system
      (ARS). Results from this poll and two similar polls from previous years are
      discussed.

PMID- 30289775
TI  - Enhanced triage for patients with suspected cardiac chest pain: the History and
      Electrocardiogram-only Manchester Acute Coronary Syndromes (HE-MACS) decision
      aid.
AB  - OBJECTIVES: Several decision aids can 'rule in' and 'rule out' acute coronary
      syndromes (ACS) in the Emergency Department (ED) but all require measurement of
      blood biomarkers. A decision aid that does not require biomarker measurement
      could enhance risk stratification at triage and could be used in the prehospital
      environment. We aimed to derive and validate the History and ECG-only Manchester
      ACS (HE-MACS) decision aid using only the history, physical examination and ECG.
      METHODS: We undertook secondary analyses in three prospective diagnostic accuracy
      studies that included patients presenting to the ED with suspected cardiac chest
      pain. Clinicians recorded clinical features at the time of arrival using a
      bespoke form. Patients underwent serial troponin sampling and 30-day follow-up
      for the primary outcome of ACS. The model was derived by logistic regression in
      one cohort and validated in two similar prospective studies. RESULTS: The HE-MACS
      model was derived in 796 patients and validated in cohorts of 474 and 659
      patients. HE-MACS incorporated age, sex, systolic blood pressure plus five
      historical variables to stratify patients into four risk groups. On validation,
      5.5 and 12.1% (pooled total 9.4%) patients were identified as 'very low risk'
      (potential immediate rule out) with a pooled sensitivity of 99.5% (95% confidence
      interval: 97.1-100.0%). CONCLUSION: Using only the patient's history and ECG, HE
      MACS could 'rule out' ACS in 9.4% of patients while effectively risk stratifying
      remaining patients. This is a very promising tool for triage in both the
      prehospital environment and ED. Its impact should be prospectively evaluated in
      those settings. 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- 30289777
TI  - Clinical Overview and Considerations for the Management of Opioid-induced
      Constipation in Patients with Chronic Noncancer Pain.
AB  - OBJECTIVES: Opioid analgesics may be associated with chronic adverse effects,
      such as opioid-induced constipation (OIC). Available and emerging prescription
      medications for OIC in patients with chronic noncancer pain are described,
      including concerns and challenges associated with OIC management. METHODS:
      Narrative review. RESULTS: Opioid-induced constipation is characterized by a
      change in bowel habits and defecation patterns that occurs when initiating opioid
      therapy and is associated with reduced bowel frequency, straining, sensation of
      incomplete evacuation, and/or patient distress related to bowel habits.
      Prescription medications are indicated when OIC persists despite conservative
      approaches (eg, increased fiber and fluid intake, exercise, over-the-counter
      laxatives and stool softeners). Phase 3 studies have demonstrated the efficacy of
      peripherally acting u-opioid receptor antagonists (PAMORA; methylnaltrexone,
      naloxegol, naldemedine), and a chloride channel activator (lubiprostone) for
      improving OIC in patients with chronic noncancer pain. While head-to-head studies
      are lacking, a meta-analysis demonstrated that MU -opioid receptor antagonists
      were more effective than placebo for the treatment of OIC. The most common
      adverse effects associated with prescription medications for OIC are
      gastrointestinal-related (eg, nausea, diarrhea, abdominal pain or distention),
      with most being mild or moderate in severity. Therapy currently in development
      for OIC includes the PAMORA axelopran. DISCUSSION: Health care providers should
      be aware of this complication in patients receiving opioids and should monitor
      and address constipation-related symptoms to optimize pain management and improve
      patient quality of life.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- 30289776
TI  - Effect of hemorheological parameters on myocardial injury after primary or
      elective percutaneous coronary intervention.
AB  - BACKGROUND: Abnormal blood viscosity favors atherosclerosis owing to endothelial
      dysfunction and changes in shear stress. Its effect on coronary microvasculature
      during percutaneous coronary intervention (PCI) is still unknown. We aimed to
      investigate the role of hemorheological parameters in the incidence of
      microvascular obstruction (MVO) and the periprocedural necrosis after primary or
      elective PCI, and secondarily, we evaluated their prognostic significance.
      MATERIALS AND METHODS: We enrolled 25 patients with ST-elevation myocardial
      infarction (STEMI), 30 patients with non-ST-elevation myocardial infarction
      (NSTEMI), and 30 patients with stable angina (SA) undergoing PCI. MVO in patients
      with STEMI and periprocedural necrosis in patients with NSTEMI and those with SA
      were assessed using angiographic/electrocardiographic and laboratory methods,
      respectively. Hemorheological profile included blood viscosity (eta) at shear
      rates 200 s and 1 s, the erythrocyte aggregation index (eta1/eta200), and plasma
      viscosity. Major adverse cardiovascular events occurrence was evaluated at follow
      up. RESULTS: Patients with STEMI experiencing angiographic MVO (28%) had higher
      eta200 (5.42+/-1.28 vs. 3.98+/-1.22 mPa[BULLET OPERATOR]s; P=0.015). Similarly,
      patients with STEMI experiencing electrocardiographic MVO (56%) had higher eta200
      (4.58+/-0.36 vs. 3.94+/-0.19 mPa[BULLET OPERATOR]s; P<0.001). Among patients with
      SA and patients with NSTEMI, those experiencing periprocedural necrosis (23.3%)
      had higher eta200 (5.30+/-0.86 vs. 4.37+/-0.88 mPa[BULLET OPERATOR]s; P=0.001),
      eta1 (19.52+/-9.62 vs. 13.29+/-7.65 mPa[BULLET OPERATOR]s; P=0.015) and
      eta1/eta200 values (3.64+/-1.50 vs. 2.72+/-0.92; P=0.007). These significant
      differences were maintained after adjustment for age, sex, and cardiovascular
      risk factors. At follow-up (30+/-6 months), 25 (29.4%) patients presented major
      adverse cardiovascular events, and they had higher eta200 (5.18+/-1.00 vs. 4.25+/
      1.01 mPa[BULLET OPERATOR]s; P<0.001). CONCLUSION: In patients undergoing either
      urgent or elective PCI, hemorheological parameters might contribute to myocardial
      injury and, if furtherly confirmed, to an unfavorable outcome.

PMID- 30289778
TI  - 2018 HONOR ROLL AWARD: Presented to RANDALL E. SCOTT at the 63rd Annual Meeting
      of the Health Physics Society Cleveland, Ohio 15-19 July 2018.

PMID- 30289780
TI  - 2018 Health Physics Society 50-Year Members And Fellow Class: Presented at the
      63rd Annual Meeting of the Health Physics Society Cleveland, Ohio 15-19 July
      2018.

PMID- 30289779
TI  - 2018 Joyce P. Davis Memorial Award: Presented to CHARLES E. ROESSLER at the 63rd
      Annual Meeting of the Health Physics Society Cleveland, Ohio 15-19 July 2018.

PMID- 30289781
TI  - 2018 Health Physics Society Military Health Physics Section John C. Taschner
      Leadership Award: Presented to CAPTAIN JOHN J. CARDARELLI II at the 63rd Annual
      Meeting of the Health Physics Society Cleveland, Ohio 15-19 July 2018.

PMID- 30289782
TI  - 2018 William a. Mcadams Outstanding Service Award: Presented to GOVIND R. RAO at
      the 63rd Annual Meeting of the Health Physics Society Cleveland, Ohio 15-19 July
      2018.

PMID- 30289784
TI  - 2018 HEALTH PHYSICS SOCIETY LECTURESHIPS: Presented at the 63rd Annual Meeting of
      the Health Physics Society Cleveland, Ohio 15-19 July 2018.

PMID- 30289783
TI  - 2018 Health Physics Society Founders Award: Presented to HOWARD W. DICKSON at the
      63rd Annual Meeting of the Health Physics Society Cleveland, Ohio 15-19 July
      2018.

PMID- 30289785
TI  - 2018 Health Physics Society Homeland Security Section Service Award: Presented to
      BROOKE ROBERT BUDDEMEIER at the 63rd Annual Meeting of the Health Physics Society
      Cleveland, Ohio 15-19 July 2018.

PMID- 30289787
TI  - 2018 Health Physics Society Student Science Awards: Presented at the 63rd Annual
      Meeting of the Health Physics Society Cleveland, Ohio 15-19 July 2018.

PMID- 30289786
TI  - 2018 Health Physics Society Nonionizing Radiation Section Service Award:
      Presented to DAVID H. SLINEY at the 63rd Annual Meeting of the Health Physics
      Society Cleveland, Ohio, 15-19 July 2018.

PMID- 30289788
TI  - Comparing the International Classification of Functioning, Disability, and Health
      Core Sets for Hearing Loss and Otorhinolaryngology/Audiology Intake Documentation
      at Mayo Clinic.
AB  - OBJECTIVES: The International Classification of Functioning, Disability, and
      Health (ICF) Core Sets for Hearing Loss (CSHL) consists of short lists of
      categories from the entire ICF classification that are thought to be the most
      relevant for describing the functioning of persons with hearing loss. A
      comprehensive intake that covers all factors included in the ICF CSHL holds the
      promise of developing a tailored treatment plan that fully complements the
      patient's needs. The Comprehensive CSHL contains 117 categories and serves as a
      guide for multiprofessional, comprehensive assessment. The Brief CSHL includes 27
      of the 117 categories and represents the minimal spectrum of functioning of
      persons with HL for single-discipline encounters or clinical trials. The authors
      first sought to benchmark the extent to which Audiologist (AUD) and
      Otorhinolaryngologist (ORL) discipline-specific intake documentation, as well as
      Mayo Clinic's multidisciplinary intake documentation, captures ICF CSHL
      categories. DESIGN: A retrospective study design including 168 patient records
      from the Department of Otorhinolaryngology/Audiology of Mayo Clinic in
      Jacksonville, Florida. Anonymized intake documentation forms and reports were
      selected from patient records filed between January 2016 and May 2017. Data were
      extracted from the intake documentation forms and reports and linked to ICF
      categories using pre-established linking rules. "Overlap," defined as the
      percentage of ICF CSHL categories represented in the intake documentation, was
      calculated across document types. In addition, extra non-ICF CSHL categories (ICF
      categories that are not part of the CSHL) and extra constructs (constructs that
      are not part of the ICF classification) found in the patient records were
      described. RESULTS: The total overlap of multidisciplinary intake documentation
      with ICF CSHL categories was 100% for the Brief CSHL and 50% for the
      Comprehensive CSHL. Brief CSHL overlap for discipline-specific documentation fell
      short at 70% for both AUD and ORL. Important extra non-ICF CSHL categories were
      identified and included "sleep function" and "motor-related functions and
      activities," which mostly were reported in relation to tinnitus and vestibular
      disorders. CONCLUSION: The multidisciplinary intake documentation of Mayo Clinic
      showed 100% overlap with the Brief CSHL, while important areas of nonoverlap were
      identified in AUD- and ORL-specific reports. The ICF CSHL provides a framework
      for describing each hearing-impaired individual's unique capabilities and needs
      in ways currently not documented by audiological and otological evaluations,
      potentially setting the stage for more effective individualized patient care.
      Efforts to further validate the ICF CSHL may require the involvement of
      multidisciplinary institutions with commonly shared electronic health records to
      adequately capture the breath of the ICF CSHL.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- 30289789
TI  - Vesicular hand dermatitis.
AB  - Vesicular hand dermatitis is a type of eczema involving the fingers, hands, and
      sometimes the feet. It is common in primary care, requiring prompt treatment to
      prevent chronicity. The cause is often unknown, making the condition challenging
      to treat. Management consists of avoiding irritants and using emollients and
      topical corticosteroids.

PMID- 30289790
TI  - Comparisons of Health Promoting Behavior, Depression, and Life Satisfaction
      Between Older Adults in Rural Areas in South Korea Living in Group Homes and at
      Home.
AB  - BACKGROUND: In South Korea, population aging is advancing at a more rapid rate in
      rural areas than urban areas, leading to a particularly high percentage of rural
      dwelling older adults. PURPOSE: The aim of this study was to examine and compare
      health promoting behaviors, depression, and life satisfaction between rural
      dwelling older adults who live, respectively, in group homes and at home.
      METHODS: A cross-sectional descriptive study design was employed. Study
      participants included 160 older adults aged 65 years and older who were living in
      group homes (n = 80) and at home (n = 80) in Gyeonggi province, South Korea. The
      Health Promotion Lifestyle Profile-II was used to examine health promoting
      behaviors, the Korean Geriatric Depression Screening Scale was used to examine
      depression, and the Life Satisfaction Index was used to examine life
      satisfaction. Data were analyzed using SPSS Version 21.0. RESULTS: The data
      showed significant differences between the two groups in terms of health
      promoting behaviors (t = -9.035, p < .001), depression (t = 20.861, p < .001),
      and life satisfaction (t = -12.153, p < .001). CONCLUSIONS/IMPLICATIONS FOR
      PRACTICE: The mean scores for health promotion behaviors and life satisfaction
      were higher, and the mean score for depression was lower in the group-home group
      than the at-home group. The findings from this study may be employed as basic
      data for establishing residence-appropriate nursing intervention protocols for
      older adults living in rural areas.

PMID- 30289791
TI  - DOCUMENTATION OF A NEW CHOROIDAL NEVUS.
AB  - PURPOSE: To describe the occurrence of an acquired choroidal nevus in a 73-year
      old white man. METHODS: Case report. RESULTS: A 73-year-old white man was
      referred for an evaluation and treatment of macular changes in his left eye
      consistent with pachychoroid neovasculopathy. Baseline funduscopic examination
      and color fundus photographs showed two small peripheral choroidal nevi in the
      right eye and a single small choroidal nevus in the far temporal macula of the
      left eye. Treatment with intravitreal aflibercept was initiated in the left eye
      on a treat-and-extend dosing regimen. Approximately 1 year later, a new pigmented
      choroidal lesion was detected in the left macula in an area where previous high
      resolution color fundus photographs had shown no abnormal pigmentation. Swept
      source optical coherence tomography of the new pigmented lesion showed flat
      hyperreflectivity within the inner choroid consistent with a small choroidal
      nevus. The patient was referred to his internist who found no evidence of an
      occult malignancy. Over the course of more than 4 additional years of continuous
      follow-up, the new choroidal nevus remained stable, no new fundus abnormalities
      were detected in either eye, and the patient remained medically stable.
      CONCLUSION: To the best of our knowledge, this is the first documented case of a
      new choroidal nevus. Multimodal imaging performed before lesion detection and
      over the ensuing 4 years showed its stability, thus allowing for the conclusion
      that it was a benign choroidal nevus rather than a neoplastic or paraneoplastic
      process.

PMID- 30289792
TI  - Recurrent Superior Oblique Myokymia Treated by Distal Tendon Extirpation.
AB  - BACKGROUND: We describe successful surgical treatment of superior oblique
      myokymia, which had recurred after superior oblique tenectomy. METHODS: Single
      case report. RESULTS: The distal stump of the superior oblique tendon was
      extirpated by stripping it from the globe. The ipsilateral superior rectus muscle
      also was recessed, to correct a hypertropia that had resulted from the original
      superior oblique tenectomy. CONCLUSIONS: Complete removal of the distal superior
      oblique muscle tendon provided definitive relief of superior oblique myokymia.
      Superior rectus muscle recession, combined with previous inferior oblique
      myectomy, compensated effectively for loss of superior oblique function.

PMID- 30289793
TI  - Optical Coherence Tomography Angiography Findings in Superior Segmental Optic
      Nerve Hypoplasia.

PMID- 30289794
TI  - Implementation of a Hip Fracture Care Pathway Using Lean Six Sigma Methodology in
      a Level I Trauma Center.
AB  - INTRODUCTION: The application of Lean Six Sigma (LSS) methodology with regard to
      hip fracture care remains unexamined. The aim of this study is to illustrate the
      application of LSS principles in the implementation of a hip fracture integrated
      care pathway (ICP). METHODS: A multidisciplinary team at a level I trauma center
      formed a hip fracture ICP using LSS principles. An ICP aimed toward decreasing
      time to surgery to <48 hours was implemented in April 2012. RESULTS: A total of
      505 hip fracture patients met inclusion criteria. A total of 221 patients entered
      the preimplementation cohort, and 284 were incorporated in the postimplementation
      cohort. The percentage of patients who received surgical fixation beyond 48 hours
      significantly decreased (9.50% versus 4.23%; P = 0.01). Significantly more
      complications were detected in the postimplementation cohort (62.44% versus
      80.10%; P < 0.01). The postimplementation cohort showed a significantly shorter
      length of stay (P = 0.02) and decreased hospital cost (P = 0.016). CONCLUSION:
      Our findings suggest that using LSS methods in an ICP at our institution resulted
      in markedly greater percentage of patients receiving surgical care within 48
      hours, greater detection of complication, and reduced resource consumption.

PMID- 30289795
TI  - Prescription Opioid Type and the Likelihood of Prolonged Opioid Use After
      Orthopaedic Surgery.
AB  - INTRODUCTION: A common belief is that some narcotic medications have a higher
      association with prolonged use. We assessed whether the initial opiate type
      prescribed to postoperative, opiate-naive orthopaedic trauma patients was
      associated with prolonged opioid use. METHODS: We studied 17,961 adult, opiate
      naive patients treated for a surgical musculoskeletal injury. Discharge
      prescription in morphine milligram equivalents (MMEs, a standardized dosing unit
      that allows for comparison across opioid types) was calculated. Opioid
      prescribing beyond 90 days after injury was defined as prolonged use. RESULTS:
      Initial analysis demonstrated a higher likelihood of prolonged use for patients
      discharged on hydromorphone or morphine versus hydrocodone. However, when we
      adjusted for discharge MME, only opioid quantity was predictive of prolonged use
      (P < 0.001). In addition, discharge MME was associated with opioid type (P <
      0.01). DISCUSSION: Persistent opiate use was associated with discharge opioid
      quantity, not the opioid type. These results highlight the importance of
      calculating equivalence doses when selecting opioid types and considering amount
      of narcotics prescribed. LEVEL OF EVIDENCE: Level III.

PMID- 30289796
TI  - Robotic-assisted Medial Unicompartmental Knee Arthroplasty: Options and Outcomes.
AB  - Medial unicompartmental knee arthroplasty (UKA) has several benefits over total
      knee arthroplasty for the surgical treatment of isolated medial compartmental
      arthritis in the knee, including reduced surgical risk and postoperative
      morbidity, rapid recovery, more normal kinematics, greater patient satisfaction,
      and shorter hospitalization. Nonetheless, there is substantial concern about the
      higher revision rates and lower survivorship in UKA compared to those in total
      knee arthroplasty. Robotic assistance has been advanced to improve the precision
      of bone preparation, component alignment, and quantified ligament balance in UKA,
      with the ultimate goal of improving kinematics and implant survivorship. Two
      currently available semiautonomous robotic platforms have demonstrated improved
      accuracy, and emerging short-term follow-up has demonstrated satisfactory
      functional outcomes. Further studies will be needed to determine if these
      technologies indeed have a meaningful impact on patient outcomes and survivorship
      in the mid- to long term.

PMID- 30289797
TI  - Total Hip Arthroplasty for Posttraumatic Conditions.
AB  - Posttraumatic arthritis accounts for a notable share of secondary osteoarthritis
      about the hip joint. Compared with total hip arthroplasty for primary
      osteoarthritis or inflammatory arthritis, total hip arthroplasty for
      posttraumatic arthritis offers greater technical challenges because of bone
      deformities and retained implants. Careful preoperative evaluation is necessary
      to prepare the approach, hardware removal strategy, and implants necessary to
      address bone deficiencies. Although arthroplasty is a highly successful procedure
      for posttraumatic arthritis, the results are less favorable than surgery for
      primary osteoarthritis. It is associated with a higher incidence of
      intraoperative and postoperative complications, including periprosthetic
      fractures, infection, instability, and decreased survivorship.

PMID- 30289798
TI  - Incidence and Risk Factors Associated with Venous Thromboembolism After
      Orthopaedic Below-knee Surgery.
AB  - INTRODUCTION: Among patients undergoing below-knee orthopaedic surgery, no
      consensus exists regarding the need for or type of postoperative prophylaxis to
      prevent venous thromboembolic (VTE) events. The purpose of this study was to
      assess the incidence and risk factors associated with symptomatic VTE among
      orthopaedic patients undergoing below-knee surgery who were subject to different
      types of pharmacologic thromboprophylactic strategies. METHODS: A total of 20,043
      adult patients who underwent surgery for a below-knee orthopaedic condition
      between August 2005 and August 2015 were identified. Retrospective chart review
      recorded patient demographics, comorbid data, and anatomic location of any
      procedures performed. Multivariable logistic regression analysis was used to
      determine factors associated with postoperative development of symptomatic VTE
      among patients receiving various thromboprophylactic regimens. RESULTS: The
      incidence of symptomatic VTE in patients who underwent below-knee surgery was
      2.5% (492/20,043). For patients who did not receive thromboprophylaxis, the
      incidence was 1.5% (134/9,127 patients). In this group, risk factors for
      developing VTE were male sex; nonwhite race; surgery performed below the knee but
      above the ankle; combination procedures of the forefoot/midfoot, hindfoot/ankle,
      and/or lower leg; history of VTE; and Charlson Comorbidity Index score greater
      than 2. Among patients who received an antiplatelet agent, the VTE incidence was
      1.7% (33/1,992 patients). The incidence of VTE among patients who received an
      oral or injectable anticoagulant was 3.6% (325/8,924 patients). In this group,
      risk factors for developing VTE were male sex; surgery performed below the knee
      but above the ankle; combination procedures of the forefoot/midfoot,
      hindfoot/ankle, and/or lower leg; and history of VTE. CONCLUSION: Allowing for
      different types of thromboprophylactic strategies, the results of this study
      demonstrate a higher rate of symptomatic thromboembolic disease compared with
      previously reported <1% VTE incidence rates among orthopaedic patients undergoing
      below-knee surgery. Certain patients are at higher risk for thromboembolic
      disease after below-knee orthopaedic surgery. This risk was not found to be
      lowered by thromboprophylaxis as performed in patients in this database. Future
      research should be directed at determining what the best thromboprophylactic
      strategies are for lowering this risk. LEVEL OF EVIDENCE: Therapeutic study level
      III.

PMID- 30289799
TI  - Specialty Focus: Lower Extremity, Hip and Knee Issue.

PMID- 30289800
TI  - Neurodevelopmental outcomes in HIV-infected and uninfected African children.
AB  - OBJECTIVE: HIV infection is associated with cognitive impairments, but outcomes
      are poorly explored in children starting antiretroviral therapy (ART) early or in
      those exposed but uninfected. DESIGN: Nested cross-sectional evaluation of the
      neurocognitive and behavioural outcomes of HIV-infected, HIV-exposed uninfected
      (HEU) and HIV-unexposed (HUU) Cameroonian children at age 4-9 years prospectively
      followed. METHODS: Cognitive development was assessed in 127 HIV-infected, 101
      HEU, 110 HUU children using the KABC-II, neurologic dysfunction using the Touwen
      examination and behavioural difficulties using the Strength and Difficulties
      Questionnaire (SDQ). Analyses were adjusted for children age, sex and primary
      language. Contextual factors were included in a second step to assess their
      effects on outcomes. RESULTS: All HIV-infected children were treated before 12
      months. There was a negative linear gradient in KABC-II scores from HUU children
      to HEU and HIV-infected children [gradient: -6.0 (-7.7; -4.3) for nonverbal
      index, NVI, and -8.8 (-10.7; -6.8) for mental processing index, MPI]. After
      adjusting for contextual factors, scores of HEU children were not significantly
      different from those of HUU children (all P > 0.1) and differences between HIV
      uninfected and HUU children reduced [NVI: from -11.9 (-15.3; -8.5) to -3.4 (-6.8;
      -0.01), MPI: from -17.6 (-21.3; -13.8) to -5.5 (-9.3; -1.7)]. Compared with
      uninfected children, HIV-infected children had more neurological dysfunctions and
      higher SDQ scores (P = 0.002). CONCLUSION: Despite early ART, perinatal-HIV
      infection is associated with poorer neurocognitive scores and increased
      behavioural difficulties during childhood. Contextual factors play an important
      role in this association, which emphasizes the need for early nutritional and
      developmental interventions targeting both HIV-affected infants and their
      relatives.

PMID- 30289801
TI  - HIV messaging on Twitter: an analysis of current practice and data-driven
      recommendations.
AB  - OBJECTIVES: Social media messages have been increasingly used in health campaigns
      about prevention, testing, and treatment of HIV. We identified factors leading to
      the retransmission of messages from expert social media accounts to create data
      driven recommendations for online HIV messaging. DESIGN AND METHODS: We sampled
      20 201 HIV-related tweets (posted between 2010 and 2017) from 37 HIV experts.
      Potential predictors of retransmission were identified based on prior literature
      and machine learning methods, and were subsequently analyzed using multilevel
      negative binomial models. RESULTS: Fear-related language, longer messages, and
      including images (e.g. photos, gif, or videos) were the strongest predictors of
      retweet counts. These findings were similar for messages authored by HIV experts,
      and also messages retransmitted by experts, but created by nonexperts (e.g.
      celebrities or politicians). CONCLUSIONS: Fear appeals affect how much HIV
      messages spread on Twitter, as do structural characteristics, like the length of
      the tweet and inclusion of images. A set of five data-driven recommendations for
      increasing message spread is derived and discussed in the context of current
      centers for disease control and prevention social media guidelines.

PMID- 30289802
TI  - Randomized controlled trial of a community-based intervention on HIV and
      nutritional outcomes at 6 months among women living with HIV/AIDS in rural India.
AB  - OBJECTIVE: To assess the impact of nurse-led Asha (Accredited Social Health
      Activist)-support behavioral and nutritional intervention among women living with
      HIV/AIDS (WLH/A) in rural India. DESIGN: Cluster randomized controlled trial.
      METHODS: Sixteen Primary Health Centers serving WLH/A in Andhra Pradesh were
      grouped into four regional clusters that were randomly allocated into one of four
      arms. All four groups included Asha-support and consisted of: Asha-support only
      (control group); nutrition education; nutrition supplementation; and the
      combination of supplementation and education. Differences between baseline and 6
      month follow-up for key physiological outcomes (BMI, CD4 cell count) were
      analyzed using factorial mixed models that accounted for geographic clustering.
      RESULTS: At 6 months, all groups improved CD4 cell count: Asha only [mean
      difference score (D) = 343.97, standard deviation (SD) = 106.94], nutrition
      education (D = 356.15, SD = 0.69), nutrition supplement (D = 469.66, SD = 116.0),
      and nutrition supplement and education (D = 530.82, SD = 128.56). In
      multivariable models, Asha-support and nutrition, and Asha-support and nutrition
      supplement interventions demonstrated independent significant improvements in CD4
      cell count; the interaction term was significant [estimate = 529.9; 95%
      confidence interval (CI) 512.0, 547.8; P = 0.006]. BMI also increased for all
      groups: Asha only (D = 0.95, SD = 0.82), Asha and nutrition education (D = 1.28,
      SD = 0.53), Asha and nutrition supplement (D = 2.38, SD = 0.60), nutrition
      supplement, and nutrition supplement and education (D = 2.72, SD = 0.84).
      Nutrition supplementation and nutrition education demonstrated independent
      effects on BMI; the interaction term was not significant (estimate = 0.27; 95% CI
      = 2.5, 2.7; P = 0.80). CONCLUSION: Interventions supported by community workers
      were efficacious at improving physiological outcomes and may be beneficial at
      meeting critical healthcare needs of vulnerable WLH/A in India.

PMID- 30289803
TI  - Sex differences in HIV-associated cognitive impairment: an observational cohort
      study.
AB  - OBJECTIVE: We determined whether there are sex differences in the prevalence and
      profile of HIV-associated neurocognitive impairment, and whether sex moderates
      the effect of HIV-serostatus on neurocognitive impairment among HIV+ and HIV-
      individuals. Secondarily, we assessed whether differences were explained by
      greater biopsychosocial risk factors in HIV+ women. DESIGN: Observational cohort
      study. METHODS: Analyses included 1,361 HIV+ (204 women) and 702 HIV- (214 women)
      (ages = 18-79) participants from the UCSD HIV Neurobehavioral Research Program.
      Demographically-corrected standardized T-scores from 15 neuropsychological tests
      were used to calculate domain-specific and global deficit scores (GDS). GDS>=0.5
      defined neurocognitive impairment. Biopsychosocial risk factors included low
      education, low reading level (education quality), lifetime substance use
      disorders, depressed mood (clinically-significant depressive symptoms and/or
      current major depressive disorder), and a cumulative syndemic count (sum of
      biopsychosocial risk factors, range = 0-4). Race-stratified analyses were
      conducted. Analyses were adjusted for relevant demographic and clinical factors.
      RESULTS: HIV-associated neurocognitive impairment was more prevalent in women
      versus men; however, the difference was eliminated after adjustment for reading
      level. In sex-stratified logistic regressions, the association between HIV
      seropositivity and higher likelihood of neurocognitive impairment was stronger in
      women versus men; however, the association was attenuated in women, but not men,
      after adjusting for reading level. These results in the overall sample were
      specific to blacks. Sex differences in the profile of HIV-associated
      neurocognitive impairment varied by race. CONCLUSIONS: Women, particularly black
      women, were most at-risk for HIV-associated neurocognitive impairment. Higher
      rates of HIV-associated neurocognitive impairment in women versus men may reflect
      differences in educational quality.

PMID- 30289804
TI  - Impact of universal antiretroviral therapy for pregnant and postpartum women on
      antiretroviral therapy uptake and retention.
AB  - OBJECTIVE: Universal eligibility for lifelong antiretroviral therapy (ART) for
      pregnant and breastfeeding women ('Option B+') has been widely adopted, but
      concerns remain. We tested the hypothesis that the change from CD4-guided ART
      eligibility ('Option A'), to Option B+, would improve maternal ART uptake and
      retention. DESIGN: A stepped-wedge evaluation at 12 health facilities in
      eSwatini. METHODS: Primary outcome was maternal retention: proportion of women
      attending clinic within 56 days of delivery (antenatal retention) and clinic
      attendance within 84 days of 6-months postpartum (postnatal retention).
      Generalized estimating equations examined impact of Option B+ vs. Option A.
      RESULTS: Between 19 August 2013 and 29 August 2014, 2347 HIV-positive women, 55%
      (n = 1296) Option A, 45%, (n = 1051) Option B+ were included. ART initiation was
      observed in 36% (n = 469) of Option A women vs. 94% (n = 983) under Option B+ (P
      < 0.001). Overall 39% (n = 912) were retained from first ANC visit through 6
      months postpartum. Retention was higher under Option B+ (53%, n = 559) vs. Option
      A (24%, n = 353) with variation by site and study month. Adjusting for age,
      gestational age, previous HIV diagnosis, and CD4, Option B+ women were
      significantly more likely to be retained antenatally (aRR 1.32; 95% CI 1.18-1.49;
      P < 0.001) and postnatally (aRR 2.11; 95% CI 1.79-2.49) compared with Option A.
      Restricted to women initiating ART, retention was lower under Option B+ (57%, n =
      558) vs. Option A (66%, n = 309; aRR, 0.82; 95% CI 0.70-0.95; P < 0.0001).
      CONCLUSION: Compared with CD4-guided ART eligibility, universal ART resulted in
      substantial increases in pregnant women initiating ART and retained in care
      through 6 months postpartum.

PMID- 30289805
TI  - Phase I clinical trial of an intranodally administered mRNA-based therapeutic
      vaccine against HIV-1 infection.
AB  - OBJECTIVE: The efficacy of therapeutic vaccines against HIV-1 infection has been
      modest. New inerts to redirect responses to vulnerable sites are urgently needed
      to improve these results. DESIGN: We performed the first-in-human clinical trial
      with naked mRNA (iHIVARNA) combining a dendritic cell activation strategy
      (TriMix:CD40L+CD70+caTLR4 RNA) with a novel HIV immunogen sequences (HTI
      immunogen). METHODS: A dose escalation, phase I clinical trial was performed in
      21 chronic HIV-1-infected patients under ART who received three intranodal doses
      of mRNA (weeks 0, 2 and 4) as follow: TriMix-100 g, TriMix-300 g, TriMix-300 g
      with HTI-300 g, TriMix-300 g with HTI-600 g, TriMix-300 g with HTI-900 g. Primary
      end-point was safety and secondary-exploratory end-points were immunogenicity,
      changes in viral reservoir and transcriptome. RESULTS: Overall, the vaccine was
      secure and well tolerated. There were 31 grade 1/2 and 1 grade 3 adverse events,
      mostly unrelated to the vaccination. Patients who received the highest dose
      showed a moderate increase in T-cell responses spanning HTI sequence at week 8.
      In addition, the proportion of responders receiving any dose of HTI increased
      from 31% at w0 to 80% postvaccination. The intervention had no impact on caHIV
      DNA levels, however, caHIV-RNA expression and usVL were transiently increased at
      weeks 5 and 6 in the highest dose of iHIVARNA, and these changes were positively
      correlated with HIV-1-specific-induced immune responses. CONCLUSION: This phase I
      dose-escalating trial showed that iHIVARNA administration was safe and well
      tolerated, induced moderate HIV-specific T-cell responses and transiently
      increased different viral replication readouts. These data support further
      exploration of iHIVARNA in a phase II study. CLINICALTRIALS. GOV IDENTIFIER:
      NCT02413645.

PMID- 30289807
TI  - Metabolic pathway activation distinguishes transcriptional signatures of CD8+ T
      cells from HIV-1 elite controllers.
AB  - OBJECTIVE: Elite controllers, defined as persons maintaining undetectable levels
      of HIV-1 replication in the absence of antiretroviral therapy, represent living
      evidence that sustained, natural control of HIV-1 is possible, at least in
      relatively rare instances. Understanding the complex immunologic and virologic
      characteristics of these specific patients holds promise for inducing drug-free
      control of HIV-1 in broader populations of HIV-1 infected patients. DESIGN: We
      used an unbiased transcriptional profiling approach to characterize CD8 T cells,
      the strongest correlate of HIV-1 immune control identified thus far, in a large
      cohort of elite controllers (n = 51); highly active antiretrovial therapy (HAART)
      treated patients (n = 32) and HIV-1 negative (n = 10) served as reference
      cohorts. METHODS: We isolated mRNA from total CD8 T cells isolated from
      peripheral blood mononuclear cell (PBMC) of each individual followed by
      microarray analysis of the transcriptional signatures. RESULTS: We observed
      profound transcriptional differences [590 transcripts, false discovery rate (FDR)
      adjusted P < 0.05] between elite controller and HAART-treated patients.
      Interestingly, metabolic and signalling pathways governed by mammalian target of
      rapamycin (mTOR) and eIF2, known for their key roles in regulating cellular
      growth, proliferation and metabolism, were among the top functions enriched in
      the differentially expressed genes, suggesting a therapeutically actionable
      target as a distinguishing feature of spontaneous HIV-1 immune control. A
      subsequent bootstrapping approach distinguished five different subgroups of elite
      controller, each characterized by distinct transcriptional signatures. However,
      despite this marked heterogeneity, differential regulation of mTOR and eIF2
      signalling remained the dominant functional pathway in three of these elite
      controller subgroups. CONCLUSION: These studies suggest that mTOR and eIF2
      signalling may play a remarkably universal role for regulating CD8 T-cell
      function from elite controllers.

PMID- 30289806
TI  - Are European HIV cohort data within EuroCoord representative of the diagnosed HIV
      population?
AB  - OBJECTIVE: HIV cohorts are an important source of clinical data for informing
      public health policies and programmes. However, the generalizability of cohort
      findings to the wider population of people diagnosed with HIV in each country
      remains unclear. In this work, we assessed the representativeness of six large
      national HIV cohorts within Europe. DESIGN AND METHODS: Individual-level cohort
      data were provided from national cohorts in France, Germany, Greece, Italy, Spain
      and the United Kingdom. Analysis focused on new HIV diagnoses reported to The
      European Surveillance System (TESSy) during three time periods (2000-2004, 2005
      2009 and 2010-2013), to allow for temporal changes. Cohort and TESSy records were
      matched and compared by age, sex, transmission mode, region of origin and CD4
      cell count at diagnosis. The probability of being included in each cohort given
      demographic characteristics was estimated and used to generate weights inversely
      proportional to the probability of being included. RESULTS: Participating cohorts
      were generally representative of the national HIV-diagnosed population submitted
      to TESSy. However, people who inject drugs, those born in a country other than
      that reporting the data, those with low CD4 cell counts at diagnosis, and those
      more than 55 years were generally underrepresented in the cohorts examined.
      CONCLUSION: These European cohorts capture a representative sample of the HIV
      diagnosed populations in each country; however some groups may be
      underrepresented.

PMID- 30289808
TI  - Inhibitory natural killer cell receptor KIR3DL1 with its ligand Bw4 constraints
      HIV-1 disease among South Indians.
AB  - OBJECTIVE: To investigate the role of genotypic and phenotypic characteristics of
      killer cell immunoglobulin-like receptors (KIRs) and their human leukocyte
      antigen (HLA) class-1 ligands in HIV-1 disease progression. STUDY DESIGN AND
      METHODS: This is a nested case-control study including 347 HIV seropositive (HIV
      1) individuals from South India constituting 45 long-term nonprogressors (LTNPs)
      and 302 disease progressors. KIR genotyping was performed by multiplex sequence
      specific primer-directed PCR (SSP-PCR). Phenotypic expressions of KIR3DL1/S1 was
      studied using multiparametric flow cytometry assay. HLA-Bw4 and Bw6 epitopes were
      determined by ARMS-PCR. HLA-Bw4, HLA-Bw4, HLA-C1, HLA-C2, and HLA-Aw4 were
      genotyped using SSP-PCR. Serum levels of IFN-gamma was quantified using ELISA
      method. RESULTS: Overall, 37 different KIR genotypes were observed and the
      distribution of genotypes with AB-AB (OR = 2.2, P = 0.033) constellations showed
      significant increase among LTNPs. The frequencies of 3DL1-2DL3-2DL5 (OR = 2.2, Pc
      = 0.031), 3DL1-Bw4/Aw4 (OR = 2.49, Pc = 0.019), homozygous Bw4 (OR = 2.422, Pc =
      0.011) were observed higher in LTNPs and 2DS1-2DS2-2DS3 (OR =  0.475, Pc = 0.03),
      homozygous Bw6 (OR = 0.413, Pc = 0.011) were higher in the disease progressors.
      Flow cytometry assay showed the increased expression and maintenance of 3DL1/S1NK
      cells in LTNPs (P = 0.0001). Further the expansion of 3DS1NK cells was higher
      than 3DL1NK cells in the heterozygous 3DL1/S1 LTNPs (P = 0.001). CONCLUSION: The
      inhibitory receptor 3DL1 with Bw4 and its A-haplotype defining KIR genes
      (2DL3/L5) confers protection against HIV-1 disease progression. An increased
      expression and maintenance of 3DL1/S1 natural killer cells may contribute to the
      efficient activation of the natural killer cells and subsequent long-term
      nonprogression (LTNPn) to the disease.

PMID- 30289810
TI  - Increase in HSV shedding at initiation of antiretroviral therapy and decrease in
      shedding over time on antiretroviral therapy in HIV and HSV-2 infected persons.
AB  - OBJECTIVES: HIV-infected persons with chronic herpesvirus infections may
      experience paradoxical worsening after initiation of antiretroviral therapy
      (ART), but the impact of longer term ART is unclear. We evaluated the
      relationships between genital herpes simplex virus (HSV) shedding and ART
      initiation and time on therapy in HIV and HSV-2-infected persons. DESIGN:
      Prospective observational study. METHODS: Rates of HSV shedding in 45 HIV and HSV
      2-infected persons on or off ART were prospectively followed over up to three,
      noncontiguous, 60-day periods, during which participants performed daily genital
      swabs for HSV detection by real-time HSV DNA PCR and reported symptoms.
      Initiation or discontinuation of ART was at the discretion of participants'
      healthcare providers. RESULTS: In all, 6425 daily genital swabs were obtained
      from 45 persons (38 men and seven women) during 105 swabbing sessions. During the
      three sessions, 67, 74, and 92% of persons were on ART. HSV was detected on 26.5%
      of days in men and 22.3% of days in women. The overall rates of genital HSV
      shedding were 19.4% of days in persons not on ART, 30.2% in persons within 90
      days of ART initiation, and 23.3% in persons on ART for longer than 90 days.
      After initiation of ART, HSV shedding decreased by 2% per month, or 23% per year
      (RR 0.98/month on ART; P = 0.0003 in adjusted analysis). This finding was
      consistent after including consideration of HIV viral load and CD4 cell count.
      CONCLUSIONS: HSV shedding increased significantly shortly after ART initiation,
      but decreased with time on prolonged ART.

PMID- 30289809
TI  - Pain in people living with HIV and its association with healthcare resource use,
      well being and functional status.
AB  - OBJECTIVE: We describe the prevalence of pain and its associations with
      healthcare resource utilization and quality-of-life. DESIGN: The POPPY Study
      recruited three cohorts: older people living with HIV (PLWH; >=50 years, n =
      699), younger demographically/lifestyle similar PLWH (less than 50 years, n =
      374) and older demographically/lifestyle similar HIV-negative (>=50 years, n =
      304) people from April 2013 to February 2016. METHODS: Current pain and pain
      related healthcare use was collected via a self-reported questionnaire. Logistic
      regression assessed between-group differences in the prevalence of pain in the
      past month and current pain after controlling for potential confounders.
      Associations between current pain and healthcare resource use, reported joint
      problems, depressive symptoms, quality-of-life and functional status were
      assessed in PLWH using Mann-Whitney U and chi-squared tests. RESULTS: Pain in the
      past month was reported by 473 out of 676 (70.0%) older PLWH, 224 out of 357
      (62.7%) younger PLWH and 188 out of 295 (63.7%) older HIV-negative controls (P =
      0.03), with current pain reported in 330 (48.8%), 134 (37.5%) and 116 (39.3%),
      respectively (P = 0.0007). Older PLWH were more likely to experience current
      pain, even after adjustment for confounders. Of those with pain in the past
      month, 56 out of 412 (13.6%) had missed days of work or study due to pain, and
      520 (59%) had seen a doctor about their pain. PLWH experiencing current pain had
      more depressive symptoms, poorer quality-of-life on all domains and greater
      functional impairment, regardless of age group. CONCLUSION: Even in the effective
      antiretroviral therapy era, pain remains common in PLWH and has a major impact on
      quality-of-life and associated healthcare and societal costs. Interventions are
      required to assist clinicians and PLWH to proactively manage pain.

PMID- 30289811
TI  - Women, incarceration and HIV: a systematic review of HIV treatment access,
      continuity of care and health outcomes across incarceration trajectories.
AB  - OBJECTIVE: The aim of this study was to systematically review the literature on
      gendered implications of incarceration for HIV outcomes and engagement in care
      for women living with HIV (WLWH). DESIGN: We systematically searched seven
      bibliographic databases, for peer-reviewed English-language studies, published
      between 2007 and 2017 reporting on incarceration, women (transgender inclusive)
      and HIV. METHODS: Articles were included for evaluation if they reported outcomes
      for at least one of three measures of interest: viral load, antiretroviral
      therapy (ART) adherence or engagement in care among WLWH along incarceration
      trajectories. RESULTS: Out of 1119 studies, 24 (2%) met the inclusion criteria.
      Of these 24 studies, the majority (n = 23) were conducted in the USA, 19 included
      samples of women and men and seven studies were transgender inclusive. Our review
      did not reveal clear sex differences in HIV outcomes during periods of
      incarceration; however, studies reporting postincarceration outcomes demonstrated
      significant sex disparities in all three outcomes of interest. Following
      incarceration, women were less likely to be virally suppressed, less likely to
      achieve optimal ART adherence and less likely to be engaged in care. CONCLUSION:
      Despite growing numbers of incarcerated WLWH globally, there is a substantial gap
      in research examining the impact of incarceration on HIV outcomes for WLWH.
      Significant sex disparities in HIV outcomes and engagement in care exist along
      incarceration trajectories for WLWH, especially postincarceration. For improved
      health outcomes, research is needed to examine the experiences of WLWH throughout
      incarceration trajectories to develop interventions tailored to the specific
      needs of WLWH both during and following incarceration.

PMID- 30289812
TI  - Predicting diabetes risk among HIV-positive and HIV-negative women.
AB  - OBJECTIVE: To assess the performance of an adapted American Diabetes Association
      (ADA) risk score and the concise Finnish Diabetes Risk Score (FINRISC) for
      predicting type 2 diabetes development in women with and at risk of HIV
      infection. DESIGN: Longitudinal analysis of the Women's Interagency HIV Study.
      METHODS: The women's Interagency HIV Study is an ongoing prospective cohort study
      of women with and at risk for HIV infection. Women without prevalent diabetes and
      3-year data on fasting blood glucose, hemoglobin A1c, self-reported diabetes
      medication use, and self-reported diabetes were included. ADA and FINRISC scores
      were computed at baseline and their ability to predict diabetes development
      within 3 years was assessed [sensitivity, specificity and area under the receiver
      operating characteristics (AUROC) curve]. RESULTS: A total of 1111 HIV-positive
      (median age 41, 60% African American) and 454 HIV-negative women (median age 38,
      63% African-American) were included. ADA sensitivity did not differ between HIV
      positive (77%) and HIV-negative women (81%), while specificity was better in HIV
      negative women (42 vs. 49%, P = 0.006). Overall ADA discrimination was suboptimal
      in both HIV-positive [AUROC = 0.64 (95% CI: 0.58, 0.70)] and HIV-negative women
      [AUROC = 0.67 (95% CI: 0.57, 0.77)]. FINRISC sensitivity and specificity did not
      differ between HIV-positive (72 and 49%, respectively) and HIV-negative women (86
      and 52%, respectively). Overall FINRISC discrimination was suboptimal in HIV
      positive [AUROC = 0.68 (95% CI: 0.62, 0.75)] and HIV-negative women [AUROC = 0.78
      (95% CI: 0.66, 0.90)]. CONCLUSION: Model performance was suboptimal in women with
      and at risk of HIV, while greater misclassification was generally observed among
      HIV-positive women. HIV-specific risk factors known to contribute to diabetes
      risk should be explored in these models.

PMID- 30289814
TI  - High prevalence of echocardiographic abnormalities in older HIV-infected children
      taking antiretroviral therapy.
AB  - BACKGROUND: Antiretroviral therapy (ART) has decreased mortality so that
      increasing numbers of children with HIV are reaching adolescence. However,
      longstanding HIV infection and/or its treatment in children is associated with
      noninfectious complications including cardiac disease. We investigated the
      prevalence, spectrum and risk factors for echocardiographic abnormalities among
      children established on ART. METHODS: HIV-infected children aged 6-16 years, on
      ART at least 6 months were enrolled into a cross-sectional study from a public
      sector paediatric HIV clinic in Harare, Zimbabwe. A standardized examination
      including transthoracic echocardiography was performed. Local echocardiographic
      reference ranges were used to define cardiac abnormalities. Logistic regression
      was used to examine the association between cardiac abnormalities and risk
      factors. RESULTS: Of the 201participants recruited, 92 (46%) were girls and
      median age was 11 (IQR 9-12) years; CD4 cell count was 727 cells/MUl (IQR 473
      935) and 154 (78%) had viral load less than 400 copies/ml. Echocardiographic
      abnormalities were found in 83 (42%); left ventricular (LV) diastolic dysfunction
      was the most common abnormality 45 (23%) and LV hypertrophy in 22 (11%). LV and
      left atrial dilatation were found in 9 (5%) and 16 (8%), respectively. Right
      ventricular dilatation and systolic dysfunction were found in 13 (7%) and 4 (2%),
      respectively, of whom 60% had concurrent left heart abnormalities. Current use of
      nevirapine was associated with LVH [aOR 3.14 (1.13-8.72; P = 0.03)] and
      hypertension was associated with LV diastolic dysfunction [aOR 3.12 (1.48-6.57; P
      < 0.01)]. CONCLUSION: HIV-infected children established on ART have a high burden
      of echocardiographic abnormalities. Right heart disease was predominantly
      associated with left heart abnormalities and may be part of a global
      cardiomyopathic process. Further studies are needed to investigate the natural
      history, aetiology, and pathogenesis of these abnormalities, so that appropriate
      monitoring and treatment strategies can be developed.

PMID- 30289813
TI  - Age-disparate partnerships and incident HIV infection in adolescent girls and
      young women in rural South Africa.
AB  - OBJECTIVE: Adolescent girls and young women (AGYW) have a much higher risk of HIV
      infection than young men of the same age. One hypothesis for this disparity is
      AGYW are more likely to be in sexual partnerships with older men with HIV;
      however, evidence has been inconclusive. DESIGN: We used longitudinal data from a
      randomized trial in South Africa (HPTN 068) to determined whether partner age
      difference is associated with incident HIV infection in AGYW. METHODS: Age
      difference was examined continuously and dichotomously (>=5 years). We examined
      inverse probability of exposure weighted survival curves and calculated time
      specific risk differences and risk ratios over 5.5 years of follow-up. We also
      used a marginal structural Cox model to estimate hazard ratios over the entire
      study period. RESULTS: Risk of HIV was higher in AGYW with an age-disparate
      partnership versus not and the risk difference was largest at later time points.
      At 5.5 years, AGYW with an age-disparate partnership had a 12.6% (95% confidence
      interval 1.9-23.3) higher risk than AGYW with no age-disparate partnerships. The
      weighted hazard ratio was 1.91 (95% confidence interval 1.33-2.74), an
      association that remained after weighting for either transactional or condomless
      sex, and after examining continuous age-differences. CONCLUSION: Age-disparate
      partnerships increased risk of HIV infection, even after accounting for
      transactional sex and condomless sex. The relationship between age-disparate
      partnerships and HIV infection may be explained by increased exposure to
      infection from men in a higher HIV prevalence pool rather than differences in
      sexual behaviour within these partnerships.

PMID- 30289815
TI  - Effectiveness of a multivitamin supplementation program among HIV-infected adults
      in Tanzania.
AB  - OBJECTIVE: The objective of this study was to assess the effectiveness of a
      routine multivitamin supplementation program for adults living with HIV in
      Tanzania. DESIGN: We conducted a retrospective cohort study of 67 707 adults
      enrolled in the Dar es Salaam HIV care and treatment program during 2004-2012.
      METHODS: The Dar es Salaam HIV care and treatment program intended to provide all
      adult patients with multivitamin supplements (vitamins B-complex, C, and E) free
      of charge; however, intermittent stockouts and other implementation issues did
      not afford universal coverage. We use Cox proportional hazard models to assess
      the time-varying association of multivitamin supplementation with mortality and
      clinical outcomes. RESULTS: The study cohort contributed 41 540 and 129 315
      person-years of follow-up time to the antiretroviral therapy (ART)-naive and ART
      experienced analyses, respectively. Among 48 207 ART-naive adults, provision of
      multivitamins reduced the risk of mortality [adjusted hazard ratio (aHR): 0.69;
      95% confidence interval (CI): 0.59-0.81], incident tuberculosis (TB) (aHR: 0.83;
      0.76-0.91), and meeting ART eligibility criteria (aHR: 0.78; 95% CI: 0.73-0.83)
      after adjustment for time-varying confounding. Among 46 977 ART-experienced
      patients, multivitamins reduced mortality (hazard ratio: 0.86; 95% CI: 0.80
      0.92), incident TB (aHR: 0.78; 95% CI: 0.73-0.84), and immunologic failure (aHR:
      0.70; 95% CI: 0.67-0.73). The survival benefits associated with provision
      multivitamins appeared to be greatest during the first year of ART and declined
      over time (P value <0.001). CONCLUSION: Multivitamin supplementation appears to
      be a simple, effective, safe, and scalable program to improve survival, reduce
      incidence of TB, and improve treatment outcomes for adult HIV patients in
      Tanzania.

PMID- 30289816
TI  - Variation in antiretroviral treatment coverage and virological suppression among
      three HIV key populations.
AB  - OBJECTIVES: We assessed differences in antiretroviral treatment (ART) coverage
      and virological suppression across three HIV key populations, as defined by self
      reported HIV transmission category: sex between men, injection drug use (IDU) and
      heterosexual transmission. DESIGN: A multinational cohort study. METHODS: Within
      the EuroSIDA study, we assessed region-specific percentages of ART-coverage among
      those in care and virological suppression (<500 copies/ml) among those on ART,
      and analysed differences between transmission categories using logistic
      regression. RESULTS: Among 12 872 participants followed from 1 July 2014 to 30
      June 2016, the percentages of ART-coverage and virological suppression varied
      between transmission categories, depending on geographical region (global P for
      interaction: P = 0.0148 for ART-coverage, P = 0.0006 for virological
      suppression). In Western [adjusted odds ratio (aOR) 1.41 (95% confidence interval
      1.14-1.75)] and Northern Europe [aOR 1.68 (95% confidence interval 1.25-2.26)],
      heterosexuals were more likely to receive ART than MSM, while in Eastern Europe,
      there was some evidence that infection through IDU [aOR 0.60 (95% confidence
      interval 0.31-1.14)] or heterosexual contact [aOR 0.58 (95% confidence interval
      0.30-1.10)] was associated with lower odds of receiving ART. In terms of
      virological suppression, people infected through IDU or heterosexual contact in
      East Central and Eastern Europe were around half as likely as MSM to have a
      suppressed viral load on ART, while we observed no differences in virological
      suppression across transmission categories in Western and Northern Europe.
      CONCLUSION: In our cohort, patterns of ART-coverage and virological suppression
      among key populations varied by geographical region, emphasizing the importance
      of tailoring HIV programmes to the local epidemic.

PMID- 30289817
TI  - CD4+ cell count recovery after combined antiretroviral therapy in the modern
      combined antiretroviral therapy era.
AB  - OBJECTIVE: To assess CD4 recovery after combined antiretroviral therapy (cART)
      initiation with sustained virologic control. DESIGN: Cohort study based on the
      French Hospital Database on HIV (FHDH-ANRS CO4). METHODS: We selected naive HIV-1
      infected individuals initiating cART between 2006 and 2014 with CD4 cell counts
      less than 500 cells/MUl who achieved virologic control, defined as two
      consecutive viral loads less than 50 copies/ml. We estimated the cumulative
      incidence of CD4 recovery at least 500 cells/MUl and identified associated
      factors, considering 'virologic failure,' 'loss to follow-up' and 'death' as
      competing events. RESULTS: We analyzed 6050 individuals with a median follow-up
      of 14.2 months since virologic control. The cumulative incidence for CD4 recovery
      after 6 years of virologic control reached 69.7%. The main factor associated with
      CD4 recovery was the CD4 count at treatment initiation [subdistribution hazard
      ratio (sHR) 9.64, 95% confidence interval (95% CI) 8.12-11.43 for CD4 cell counts
      between 350 and 500 cells/MUl compared with CD4 cell counts <100 cells/MUl). A
      higher CD4/CD8 ratio at initiation was also independently associated with a
      higher probability of CD4 recovery [sHR 1.67; 95% CI 1.34-2.09] for a CD4/CD8
      ratio >=1.00 vs. < 0.30). Higher viral load at initiation was also associated
      with a higher probability of CD4 recovery, whereas time to viral suppression was
      not. CONCLUSION: After 6 years of sustained virologic control, a large majority
      of the population achieved CD4 recovery. A higher CD4 cell count at initiation
      was a strong predictor of CD4 recovery and, to a lesser extent, a higher CD4/CD8
      ratio at initiation. These results confirm the necessity of early treatment.

PMID- 30289818
TI  - Pharmacokinetic testing of a first generation cabotegravir prodrug in rhesus
      macaques.
AB  - Long-acting antiretrovirals can improve therapy and prevention for HIV-1
      infection. Current long-acting cabotegravir (CAB LAP) can be administered every
      other month. Previously, we demonstrated that a myristoylated CAB prodrug encased
      in poloxamer 407 provided extended plasma drug concentrations. We now demonstrate
      that this first-generation nanoformulated prodrug can sustain plasma CAB
      concentrations above the PA-IC90 for four months in rhesus macaques. A 2.5-fold
      extension in CAB half-life and a 1.6-fold increase in area under the
      concentration-time curve were observed compared to CAB LAP.

PMID- 30289820
TI  - Dysbiosis in Snoring Children: an Interlink to Comorbidities?
AB  - BACKGROUND AND OBJECTIVES: Early microbial colonization has a key impact on
      infant health through nutritional, immunological, and metabolic programming. The
      origin of child snoring is multifactorial and complex, and may thereby also
      generate long-term health problems. The link between child snoring and gut
      microbes remains unclear, although indirect evidence exists regarding this
      relationship. This study aimed to characterize the connection between gut
      microbiota and child snoring. METHODS: In a prospective, observational CHILD
      SLEEP birth cohort study, gut microbiota in a subcohort of 43 of these children
      at 2 years of life was profiled with 16S ribosomal RNA gene amplicon sequencing.
      RESULTS: A higher abundance of the Proteobacteria phylum, the Enterobacteriaceae
      family, and Erysipelotrichaceae family, as well as a higher ratio of Firmicutes
      to Bacteroidetes were detected in snorers as compared to controls. Furthermore,
      snorers showed significantly lower microbial diversity and richness than non
      snorers. CONCLUSIONS: The snoring children manifest different gut microbiota as
      compared with healthy children. Considering that snoring and sleep disorders can
      be a source of long-term consequences, including cardiovascular, metabolic,
      immunological, neurocognitive and behavioural consequences, our results proposes
      early microbiota as a new treatment target.

PMID- 30289819
TI  - Targeted sequencing identifies a missense variant in the BEST3 gene associated
      with antihypertensive response to hydrochlorothiazide.
AB  - Chromosome 12q15 was identified in Genetic Epidemiology of Response Assessment
      (GERA) and replicated in Pharmacogenomic Evaluation of Antihypertensive Responses
      (PEAR) for its association with blood pressure (BP) response to
      hydrochlorothiazide (HCTZ). However, the functional variant is unknown and we
      aimed to identify the likely functional variants through targeted sequencing. The
      chromosome 12q15 region was sequenced in 397 best and worst responders to HCTZ in
      PEAR (N=199) and GERA (N=198) hypertensive study participants. Logistic
      regression was used for the association analysis adjusting for age, sex, race,
      and principal components 1 and 2. For validation, the significant single
      nucleotide polymorphism was tested for association with the change in systolic
      (DeltaSBP) and diastolic BP (DeltaDBP) post-treatment in the entire PEAR (N=370)
      and GERA (N=570) cohorts. A novel missense polymorphism (G>A, Pro383Leu) in
      BEST3, rs61747221, was significantly associated with better HCTZ response
      (P=0.0021, odds ratio=2.05). It was validated in the entire cohort of PEAR
      (DeltaSBP: P=0.021, beta=-1.60, DeltaDBP: P=0.023, beta=-1.08) and GERA
      (DeltaSBP: P=0.028, beta=-1.95, DeltaDBP: P=0.032, beta=-1.28). BEST3 encodes the
      calcium sensitive chloride channel in the vascular smooth muscle implicated in
      the regulation of BP, especially in response to vasoconstrictors like angiotensin
      II. These results suggest that BEST3 is involved in the chronic BP lowering
      mechanism of thiazides and highlight its importance as a genetic predictor of the
      BP response to thiazide diuretics.

PMID- 30289821
TI  - Parental Factors in Pediatric Functional Abdominal Pain Disorders: A Cross
      Sectional Cohort Study.
AB  - OBJECTIVES: Parental factors are suggested to play a role in pediatric irritable
      bowel syndrome (IBS) and functional abdominal pain - not otherwise specified (FAP
      NOS) and may influence treatment. Since studies on parental factors mainly focus
      on mothers, this study aims to compare physical health, psychological distress,
      personality dimensions and parenting behavior of both parents of children with
      IBS or FAP-NOS to parents of controls. METHODS: Parents of 91 children with IBS
      or FAP-NOS were included in this explorative cross-sectional cohort study.
      Parents of 74 age-matched healthy children were used as controls. Questionnaires
      were used to measure demographics, physical health, psychological distress and
      symptoms, personality dimensions and child-rearing practices. RESULTS: 59 mothers
      and 52 fathers of 61 children with IBS/FAP-NOS (response rate 61.0%) and 56
      mothers and 49 fathers of 59 controls completed the study (response rate 70.9%).
      Mothers of children with IBS/FAP-NOS reported more physical problems.
      Psychological distress and symptoms, personality dimensions and child-rearing
      practices did not differ between mothers of both groups. Fathers of children with
      IBS/FAP-NOS had significantly lower scores on the child-rearing practice subscale
      of ignoring of unwanted behavior. In the IBS/FAP-NOS group, fathers were more
      depressed and less agreeable than mothers. No differences on all assessed
      outcomes were found between parents of children with IBS and children with FAP
      NOS. CONCLUSIONS: Mothers of children with IBS/FAP-NOS and healthy peers differ
      with respect to physical health. Fathers in both groups differ with respect to
      child-rearing style. Clinicians should be aware of these differences when
      treating children with these disorders.

PMID- 30289822
TI  - Pediatric chronic inflammatory bowel disease in a German statutory health
      INSURANCE - incidence rates from 2009 - 2012.
AB  - OBJECTIVE: The incidence of pediatric inflammatory bowel disease (PIBD) varies
      over time and geographic region. We attempted to generate incidence rates form
      German health insurance data. METHODS: We used health care data for 2009-2015
      provided by BARMER, a major statutory health insurance company in Germany,
      insuring approx. 8% of the pediatric population. We applied a Canadian case
      definition for PIBD based on ICD coding, documentation of (ileo)colonoscopy and
      the number of PIBD related visits, without external validation for Germany. An
      internal validation of the specificity of the diagnosis by checking whether the
      identified incident cases had also prescriptions of PIPD specific drugs was
      performed. RESULTS: In 2012, 187 pediatric patients were newly diagnosed,
      accounting for an overall PIBD incidence of 17.41 (95%-CI: 15.08-20.10) per
      100,000 insured children and adolescents from 0-17.9 years per year compared to
      13.65/100,000 (95%-CI: 11.63-16.01) in 2009. The age specific incidence showed a
      steep increase as of the age of 7 years. The PIBD prevalence in 2012 was
      66.29/100,000. CONCLUSION: In conclusion, the incidence of PIBD in 0 -17.9-year
      olds in Germany with health BARMER health insurance in 2012 is among the highest
      reported in the literature.

PMID- 30289823
TI  - Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) Versus Standard of
      Care for Postsurgical Lagophthalmos and Exposure Keratopathy: Trends in Visual
      Outcomes.
AB  - PURPOSE: To compare baseline characteristics and visual acuity outcomes in
      patients treated with prosthetic replacement of the ocular surface ecosystem
      (PROSE) versus other standard-of-care (SOC) treatments for postsurgical
      lagophthalmos and exposure keratopathy. METHODS: An institutional review board
      approved, retrospective cohort study of 45 consecutive patients (53 eyes) with
      postsurgical lagophthalmos and exposure keratopathy following oculoplastic or
      skull base surgeries treated between August 2011 and August 2017 was performed.
      Patients treated with PROSE (22 patients, 27 eyes) were identified by referrals
      made to the PROSE treatment program at Weill Cornell Medical College. Patients
      treated with SOC treatments (23 patients, 26 eyes) were identified by
      International Classification of Diseases-9 and International Classification of
      Diseases-10 search of billing records. SOC treatments included ocular surface
      lubrication (artificial tears and/or punctal plugs), tape tarsorrhaphy and/or
      moisture chamber, or surgical correction. The primary outcome measure was best
      corrected visual acuity converted to logMAR at baseline and at 1, 3, 6, and 12
      months. Secondary outcome measures were subjective patient reports of improvement
      in vision and comfort, as well as presence of punctate epithelial erosions and/or
      corneal haze on slit-lamp examination before and after treatment. RESULTS:
      Average age for all patients was 52 +/- 22 years (range: 7-87). Twenty-eight
      (62%) of total patients were male. Baseline corrected logMAR visual acuity was
      0.58 +/- 0.40 (20/76) for PROSE and 0.27 +/- 0.39 (20/37) for SOC cohorts (p <
      0.001). Mean number of failed prior treatments was 8.3 +/- 3 for PROSE and 2.1 +/
      2 for SOC (p < 0.0001). Mean difference in logMAR visual acuity for PROSE versus
      SOC, respectively, from baseline to 1 month was 0.33 +/- 0.26 (3-line
      improvement) versus 0.01 +/- 0.17 (no line improvement; p < 0.0001), to 3 months
      was 0.31 +/- 0.23 (3-line improvement) versus 0.08 +/- 0.30 (4-letter
      improvement; p = 0.0004), to 6 months was 0.31 +/- 0.28 (3-line improvement)
      versus 0.10 +/- 0.36 (1-line improvement; p = 0.02), and to 12 months was 0.32 +/
      0.28 (3-line improvement) versus 0.12 +/- 0.34 (1-line improvement; p = 0.01).
      CONCLUSIONS: Patients with postsurgical lagophthalmos and exposure keratopathy
      treated with PROSE are more likely to have failed a higher number of treatments
      and have worse initial best-corrected visual acuities than those treated with
      SOC. Prosthetic replacement of the ocular surface ecosystem causes rapid and
      substantial visual improvement within 1 month of use compared with SOC, with
      little change beyond this time and sustained best-corrected visual acuity at 3,
      6, and 12 months after treatment.

PMID- 30289825
TI  - Low-Flow Orbital Venous Malformation Masquerading as Rhabdomyosarcoma.
AB  - A 15-month-old male was referred for biopsy of presumed rhabdomyosarcoma in the
      setting of rapidly progressing left-sided proptosis. Examination revealed left
      periorbital edema and left hypoglobus. MRI revealed a soft-tissue density mass
      within the left lateral retrobulbar space. Several days later, he developed acute
      periorbital ecchymosis and increasing edema. With high suspicion for a vascular
      lesion, a CT scan was performed with dynamic arterial and venous imaging. Central
      filling was noted in the lateral retrobulbar component with increased enhancement
      on delayed venous imaging in the middle cranial fossa component favoring the
      diagnosis of a low-flow orbital venous malformation. In the setting of
      spontaneous orbital hemorrhage and risk of future vision loss, the decision was
      made to proceed with a combined neurosurgical approach treating the intracranial
      component and debulking the orbital component. This case highlights the
      importance of thorough radiographic evaluation prior to proceeding with a
      surgical procedure in the appropriate clinical context.

PMID- 30289824
TI  - Undifferentiated Pleomorphic Sarcoma Metastatic to the Orbit.
AB  - Undifferentiated pleomorphic sarcoma is a malignancy of mesenchymal origin, which
      was previously known as malignant fibrous histiocytoma. It is known to occur on
      rare occasion as a primary orbital tumor, but no known cases of metastatic
      orbital involvement have been reported since 2002, when the reclassification of
      these tumors took place. The authors report a patient who presented with a
      metastasis to the left orbit 2 years after undergoing treatment of a high-grade
      undifferentiated pleomorphic sarcoma of the right thigh. Histopathology of the
      orbital mass was similar to the primary tumor biopsy prior to neoadjuvant
      chemotherapy and radiation. The appearance was markedly altered in the subsequent
      excisional tissue, which showed treatment changes. Immunohistochemistry and
      genetic testing also supported the metastatic nature of the orbital lesion. The
      patient's tumor progressed rapidly despite systemic targeted therapy and orbital
      exenteration was performed. At 2 years follow up, the patient remained without
      evidence of tumor recurrence in the socket.

PMID- 30289826
TI  - Magnetic Resonance Elastography: An Update.

PMID- 30289829
TI  - New and Emerging Applications of Magnetic Resonance Elastography of Other
      Abdominal Organs.
AB  - Increasing clinical experience and ongoing research in the field of magnetic
      resonance elastography (MRE) is leading to exploration of its applications in
      other abdominal organs. In this review, the current research progress of MRE in
      prostate, uterus, pancreas, spleen, and kidney will be discussed. The article
      will describe patient preparation, modified technical approach including
      development of passive drivers, modification of sequences, and inversion. The
      potential clinical application of MRE in the evaluation of several disease
      processes affecting these organs will be discussed. In an era of increasing
      adoption of multiparametric magnetic resonance imaging approaches for solving
      complex abdominal problems, abdominal MRE as a biomarker may be seamlessly
      incorporated into a standard magnetic resonance imaging examination to provide a
      rapid, reliable, and comprehensive imaging evaluation at a single patient
      appointment in the future.

PMID- 30289830
TI  - Quantifying Tumor Stiffness With Magnetic Resonance Elastography: The Role of
      Mechanical Properties for Detection, Characterization, and Treatment
      Stratification in Oncology.
AB  - The viscoelastic properties of tissue are significantly altered with the
      development of tumors and these alterations can be assessed with magnetic
      resonance elastography (MRE). Accurate detection and characterization of
      malignant and benign lesions can be obtained by quantifying tumor stiffness,
      improving the specificity and diagnostic accuracy of conventional magnetic
      resonance imaging. Furthermore, MRE can be used to stratify patients for
      treatment based on risk of normal tissue toxicity and surgical considerations
      including consistency and adherence of the tumor to surrounding structures. MRE
      is a reliable reproducible technique demonstrated in studies that include both
      patients with cancer and normal volunteers, and an average technical failure rate
      of <1%. The addition of MRE into a multiparametric magnetic resonance imaging
      assessment may improve the diagnosis and treatment of cancer.

PMID- 30289827
TI  - Stiffness and Beyond: What MR Elastography Can Tell Us About Brain Structure and
      Function Under Physiologic and Pathologic Conditions.
AB  - Brain magnetic resonance elastography (MRE) was developed on the basis of a
      desire to "palpate by imaging" and is becoming a powerful tool in the
      investigation of neurophysiological and neuropathological states. Measurements
      are acquired with a specialized MR phase-contrast pulse sequence that can detect
      tissue motion in response to an applied external or internal excitation. The
      tissue viscoelasticity is then reconstructed from the measured displacement.
      Quantitative characterization of brain viscoelastic behaviors provides us an
      insight into the brain structure and function by assessing the mechanical
      rigidity, viscosity, friction, and connectivity of brain tissues. Changes in
      these features are associated with inflammation, demyelination, and
      neurodegeneration that contribute to brain disease onset and progression. Here,
      we review the basic principles and limitations of brain MRE and summarize its
      current neuroanatomical studies and clinical applications to the most common
      neurosurgical and neurodegenerative disorders, including intracranial tumors,
      dementia, multiple sclerosis, amyotrophic lateral sclerosis, and traumatic brain
      injury. Going forward, further improvement in acquisition techniques, stable
      inverse reconstruction algorithms, and advanced numerical, physical, and
      preclinical validation models is needed to increase the utility of brain MRE in
      both research and clinical applications.

PMID- 30289832
TI  - Cerebellar Ataxia in Children: A Clinical and MRI Approach to the Differential
      Diagnosis.

PMID- 30289833
TI  - Organochlorine Levels in Plasma and Risk of Multiple Myeloma.
AB  - OBJECTIVE: The aim of this study was to estimate the association between
      organochlorine pesticides and polychlorinated biphenyls (PCBs) and multiple
      myeloma (MM). METHODS: The risk of MM from organochlorine compounds was examined
      in a population-based case-control study in British Columbia, Canada. Congeners
      of PCBs and pesticides or pesticide metabolites were measured in plasma of 325
      cases and 327 controls. RESULTS: Most organochlorine analytes showed a
      significant association with MM. The strongest association (highest vs lowest
      quartile) was oxychlordane (odds ratio = 7.44; 95% confidence interval = 4.19 to
      13.21). No heterogeneity was detected between organochlorines levels and MM
      subtypes. Only oxychlordane and beta-hexachlorocyclohexane (beta-HCCH) were
      identified as significant independent predictors of MM. CONCLUSION: Our study
      provides evidence that organochlorines contribute to the risk of MM.

PMID- 30289828
TI  - Magnetic Resonance Elastography of Liver: Current Update.
AB  - The first clinical application of magnetic resonance elastography (MRE) was in
      the evaluation of chronic liver disease (CLD) for detection and staging of liver
      fibrosis. In the past 10 years, MRE has been incorporated seamlessly into a
      standard magnetic resonance imaging (MRI) liver protocol worldwide. Liver MRE is
      a robust technique for evaluation of liver stiffness and is currently the most
      accurate noninvasive imaging technology for evaluation of liver fibrosis. Newer
      MRE sequences including spin-echo MRE and 3 dimensional MRE have helped in
      reducing the technical limitations of clinical liver MRE that is performed with
      2D gradient recalled echo (GRE) MRE. Advances in MRE technology have led to
      understanding of newer mechanical parameters such as dispersion, attenuation, and
      viscoelasticity that may be useful in evaluating pathological processes in CLD
      and may prove useful in their management.This review article will describe the
      changes in CLD that cause an increase in stiffness followed by principle and
      technique of liver MRE. In the later part of the review, we will briefly discuss
      the advances in liver MRE.

PMID- 30289835
TI  - Re: Health Status of Workers Exposed to Perfluorinated Alkylate Substances.

PMID- 30289831
TI  - Advances and Future Direction of Magnetic Resonance Elastography.
AB  - The mechanical properties of soft tissues are closely associated with a variety
      of diseases. This motivates the development of elastography techniques in which
      tissue mechanical properties are quantitatively estimated through imaging.
      Magnetic resonance elastography (MRE) is a noninvasive phase-contrast MR
      technique wherein shear modulus of soft tissue can be spatially and temporally
      estimated. MRE has recently received significant attention due to its capability
      in noninvasively estimating tissue mechanical properties, which can offer
      considerable diagnostic potential. In this work, recent technology advances of
      MRE, its future clinical applications, and the related limitations will be
      discussed.

PMID- 30289834
TI  - Health Status of Workers Exposed to Perfluorinated Alkylate Substances.

PMID- 30289836
TI  - The Arsenic Century: How Victorian Britain Was Poisoned at Home, Work, and Play:
      Erratum.

PMID- 30289837
TI  - Mortality Among Hardmetal Production Workers: Pooled Analysis of Cohort Data From
      an International Investigation: Erratum.

PMID- 30289838
TI  - PATTERNS OF EXTENDED HIGH-FREQUENCY HEARING LOSS FOLLOWING STAPES SURGERY.

PMID- 30289839
TI  - COMMENT ON "PREVENTION OF OTIC BAROTRAUMA IN AVIATION: A SYSTEMATIC REVIEW".

PMID- 30289840
TI  - RESPONSE TO COMMENT ON: "PREVENTION OF OTIC BAROTRAUMA IN AVIATION: A SYSTEMATIC
      REVIEW".

PMID- 30289841
TI  - Persistent Postural-Perceptual Dizziness-A Systematic Review of the Literature
      for the Balance Specialist.
AB  - OBJECTIVE: To present a systematic review of the current data on persistent
      postural-perceptual dizziness (PPPD), a useful and relatively new diagnosis for a
      disorder that has previously been known by many different names. In addition, to
      discuss diagnostic criteria and management strategies for this condition with the
      otologist in mind. DATA SOURCES: CINAHL, Embase, PubMed, Medline, PsycINFO,
      PubMed, Google Scholar. REVIEW METHOD: The phrase "persistent postural-perceptual
      dizziness" and its acronym "PPPD" were used. RESULTS: From 318 articles, 15 were
      selected for full analysis with respect to PPPD. Most were case-control studies,
      with one consensus paper from the Barany Society available. Overall, the
      pathophysiology of PPPD remains relatively poorly understood, but is likely to be
      a maladaptive state to a variety of insults, including vestibular dysfunction and
      not a structural or psychiatric one. Cognitive behavioral therapy, vestibular
      rehabilitation, selective serotonin uptake inhibitors (SSRIs), and serotonin
      norepinephrine reuptake inhibitors (SNRIs) all seem to have a role in its
      management. CONCLUSIONS: PPPD is useful as a diagnosis for those treating
      dizziness as it helps to define a conglomeration of symptoms that can seem
      otherwise vague and allows for more structured management plans in those
      suffering from it.

PMID- 30289842
TI  - What Effect Does Smoking Have on the Surgical Closure of Tympanic Membrane
      Perforations? A Review.
AB  - OBJECTIVES: The link between cigarette smoking and outcome following surgical
      repair of tympanic membrane perforation is unclear. The objective of this study
      was to conduct a systematic review on the link between smoking and success rate
      following surgical repair of tympanic membrane perforations. MATERIALS AND
      METHODS: Systematic review performed using the following data sources: 1)
      Cochrane central register of controlled trials (1997 to April 30, 2018), 2)
      Medline (February 1948 to April 30, 2018), and 3) Embase (1975 to April 30,
      2018). Inclusion criteria for this study was: 1) studies reporting surgical
      closure of tympanic membrane perforations in smokers, 2)primary and revision
      cases, 3) English language literature, 4) minimum follow-up period of 6 months,
      and 5) pre and postoperative audiogram. The exclusion criteria were: 1) no
      identifiable data on smokers in reported outcomes, 2) less than 6 months follow
      up, 3) no audiometric outcomes, and 4) non-English language articles. RESULTS: A
      total of 75 studies were identified on initial search and 8 were eligible for the
      study. All studies were of level 4 evidence. In these eight studies, overall
      surgical closure of tympanic membrane perforation was successful in 512/577
      (88.7%) of nonsmokers and 151/197 (76.6%) in smokers. This difference was
      statistically significant. CONCLUSIONS: Smokers may have a lower success rate
      compared against nonsmokers for surgical repair of tympanic membrane
      perforations. Our review has limitations and more prospective high-quality
      controlled trials are required to further study this association.

PMID- 30289843
TI  - Peripheral Vestibular Disorders: An Epidemiologic Survey in 70 Million
      Individuals.
AB  - BACKGROUND: Dizziness is a common complaint in medicine. Nevertheless, there is a
      lack of valid data concerning the age and gender distribution of dizziness
      disorders within a larger population. Therefore, the aim of the present study is
      to undertake a representative epidemiological survey that examines all age groups
      of an entire population and describes the age and gender distribution of the most
      common peripheral vestibular disorders. METHODS: A population-based
      epidemiological survey based on confirmed ICD-10 codes, of an entire national
      population was performed. The population-based data of 70,315,919 patients were
      leveraged, as provided by 123 statutory health insurance companies in Germany.
      Patients of all age groups were analyzed. Outcome measures were age and gender
      distribution and the prevalence of unspecific vertigo, Meniere's disease, benign
      paroxysmal positional vertigo, vestibular neuritis, and other peripheral
      vestibular disorders. RESULTS: The prevalence among the recorded diagnoses was
      6.5% (6,461/100,000 individuals), with women (N = 2,973,323; 65.4%) being
      significantly more frequently affected by vertigo than men (N = 1,570,240; 34.6%;
      p < 0.001). Vertigo is rare in childhood (i.e., up to 10-14 yr of age).
      Subsequently, the prevalence of the analyzed diseases increases with age, up to a
      peak between 74 and 94 years. CONCLUSIONS: The results demonstrate that
      peripheral vestibular disorders are common in a developed country, across all age
      groups and a specific distribution of these disorders can be identified for every
      age group and gender. The impact of these disorders on the German healthcare
      system is currently underestimated.

PMID- 30289844
TI  - Prevalence of Radiographic Cochlear-Facial Nerve Dehiscence.
AB  - OBJECTIVE: To determine the prevalence of radiographic cochlear-facial nerve
      dehiscence (CFD). STUDY DESIGN: Retrospective radiological study. SETTING: Two
      tertiary-referral centers. PATIENTS: Two hundred six temporal-bone computed
      tomography (CT) scans (405 total ears) of otology/neurotology patients from two
      academic institutions between the years 2014 and 2017. INTERVENTION: Diagnostic.
      MAIN OUTCOME MEASURES: The cochlear-facial nerve partition width (CFPW) was
      measured on coronal CT sections and defined as the shortest distance between the
      cochlear basal turn and facial nerve (FN) labyrinthine segment. We used logistics
      regression analyses to determine positive predictors for radiographic evidence of
      CFD. RESULTS: The overall prevalence of radiographic CFD was 5.4% (22/406 ears).
      9.2% of patients (19/206) had CFD. Of these 19 patients, only one patient had
      mixed hearing loss that could not be explained by any other vestibular or
      auditory etiology. Three out of 206 patients had dehiscence in both ears (1.4%).
      The average CFPW was 0.6 +/- 0.2 mm, and fallopian canal width was 1.1 +/- 0.02
      mm (n = 405). Older age, use of traditional CT scans, and thinner CT slice
      thickness were significant predictors for radiographic CFD. CONCLUSIONS: The
      radiographic prevalence of CFD is higher than what is reported in histologic
      studies, and may over-estimate the true prevalence of CFD. The clinician should
      keep this in mind when considering this as potential cause for third-window
      symptoms.

PMID- 30289845
TI  - In vivo Assessment of an Endolymphatic Hydrops Gradient Along the Cochlea in
      Patients With Meniere's Disease by Magnetic Resonance Imaging-A Pilot Study.
AB  - OBJECTIVE: To assess three strategies for evaluation and description of potential
      endolymphatic hydrops (EH) gradients along the cochlea in patients with Meniere's
      disease. STUDY DESIGN: Prospective observational study. METHODS: Ten patients
      with definite Meniere's disease revealed by magnetic resonance imaging were
      included in this prospectively conducted pilot study. The presence of cochlear
      endolymphatic hydrops as well as a potential hydrops gradient along the cochlea
      were subjectively evaluated by two readers. Furthermore, both readers performed
      planimetric measurements of the relative extent of endolymphatic hydrops in the
      cochlear turns for calculation of an apico-basal-index (ABI) and an average
      gradient slope of the endolymphatic hydrops. These models were correlated with
      the available pure tone audiometry (PTA). RESULTS: Qualitatively, 13 of 16 inner
      ears presented an apical EH distribution. The median ABI was 1.69 for patients
      with low-tone hearing loss and 1.17 for patients with a flat PTA curve (p =
      0.03). The median EH slope was 7.44 and correlated with the steepness of the PTA
      (rho = 0.583; p = 0.018). The subjective analysis and the slope model were best
      fit for prediction of a low-tone hearing loss type with sensitivities of 100%
      (specificity, 42.86%) and 88.9% (specificity, 71.4%), respectively. The inter
      reader agreement in all three approaches was considered substantial to perfect.
      CONCLUSION: The presented qualitative approach and the slope model represent
      reliable methods for the description of a potential EH gradient along the
      cochlea. Furthermore, the average EH steepness along the cochlea correlates with
      the type of hearing loss.

PMID- 30289846
TI  - Cochlear Implantation in Chronic Otitis Media: Investigation of Long-term Speech
      Comprehension and Rate of Complications.
AB  - OBJECTIVE: To analyze the long-term speech comprehension and rate of
      complications of cochlear implantation in chronic otitis media. STUDY DESIGN:
      Retrospective data analysis. SETTING: Tertiary referral center with a large
      cochlear implant program. MAIN OUTCOME MEASURE: Speech perception scores in quiet
      and background noise and rate of complications. PATIENTS: Forty ears from a total
      of 38 patients with a mean age of 63.28 +/- 2.16 years at the time of
      implantation were included. RESULTS: Patients with a history of multiple ear
      surgeries, with no alternative option for hearing restoration than a cochlear
      implant, were implanted with satisfactory results in regard to speech
      comprehension. Preoperative bone conduction PTA4 correlated to postoperative
      speech comprehension scores in background noise. The rate of complications was
      low, but higher than in cases of cochlear implantation in normal middle ears.
      CONCLUSION: Cochlear implantation in chronic otitis media can be a satisfactory
      and safe procedure, if the surgery technique and aftercare is appropriate to the
      altered anatomy.

PMID- 30289848
TI  - A Gunshot Injury to Temporal Bone: Saved by the Bone.

PMID- 30289847
TI  - Can Preoperative High Resolution Computed Tomography Be Rationalized in Adult
      Cochlear Implant Candidates?
AB  - OBJECTIVE: To establish whether criteria can be used to identify patients who do
      not need high resolution computed tomography (HRCT) scans before cochlear implant
      operations, by retrospectively applying a preoperative selection pathway, the
      Cambridge Cochlear Implant Protocol (CCIP). STUDY DESIGN: Retrospective case
      series. SETTING: Tertiary referral center, Queen Elizabeth Hospital, Birmingham,
      UK (QEHB). PATIENTS: One hundred adult patients receiving primary cochlear
      implantation (CI) operations from April 2015 to July 2016 performed at the QEHB
      who received preoperative HRCTs. MAIN OUTCOME MEASURES: Etiology of hearing loss
      and anatomical abnormalities were collected by reanalyzing HRCT scans. Patients
      were retrospectively grouped according to criteria to restrict HRCT use derived
      from the Cambridge Cochlear Implant Programme (CCIP). The two main outcomes,
      recorded management change and significant abnormalities, were compared between
      the two CCIP groups, scanned and not scanned. RESULTS: Twenty-six patients had
      significant abnormalities detected on imaging, 16 in the scanned group and 10 in
      the not scanned group (p = 0.152). Five patients had a recorded management change
      as a result of HRCT scan, four scanned group, one not scanned group (p = 0.107).
      Significant abnormalities and recorded management change were seen across all
      etiological subgroups of hearing loss. CONCLUSION: The anatomy within the
      temporal bone is variable amongst CI recipients. Recorded management change and
      significant abnormalities occurred in both CCIP groups and across many etiologies
      of hearing loss patients. No specific group, based on the etiology of their
      hearing loss could be identified that do not require preoperative HRCT.
      Therefore, it is recommended that all CI patients should continue to receive
      preoperative HRCT imaging.

PMID- 30289849
TI  - Plasma Angiopoietin-2/-1 Ratio is Elevated and Angiopoietin-2 Levels Correlate
      with Plasma Syndecan-1 Following Pediatric Trauma.
AB  - BACKGROUND: Angiopoietin-1 (Agpt-1) and Agpt-2 are cytokine regulators of
      vascular endothelial integrity. Elevated plasma Agpt-2 levels and ratios of Agpt
      2:Agpt-1 are associated with adverse outcomes in adult trauma and pediatric
      sepsis populations. However, the behavior of the angiopoietins after pediatric
      trauma has not been characterized, and their relationship to endothelial
      glycocalyx damage, indicated by plasma syndecan-1 (Syn-1) levels, has not been
      established. METHODS: We performed a secondary analysis of prospectively
      collected data from 52 pediatric trauma patients and 12 control patients at a
      level one pediatric trauma center from 2013 to 2016. We measured Agpt-1, Agpt-2,
      and Syn-1 levels from plasma taken upon hospital arrival and 24 hours after
      admission. Angiopoietin levels were compared to controls, and the correlation
      between Agpt-2 and Syn-1 was assessed. RESULTS: Plasma Agpt-1 and Agpt-2 levels
      are elevated immediately after pediatric trauma compared to controls. At 24
      hours, trauma patients demonstrated significantly elevated plasma Agpt-2:Agpt-1
      ratios relative to controls due to decline of Agpt-1 levels to near that of
      controls. Higher 24-hour Agpt-2 levels are associated with more hypoperfusion,
      and elevated 24-hour Agpt-2:Agpt-1 ratios are associated with adverse clinical
      outcomes. Significant positive correlations between Agpt-2 and Syn-1 upon
      admission and at twenty-four hours after injury were identified. CONCLUSION: Our
      findings suggest dysregulation of circulating angiopoietins after pediatric
      trauma that may be linked to endothelial glycocalyx injury. Larger prospective
      studies are needed to validate these findings and determine the relationship of
      Agpt-2 with other markers of endotheliopathy.

PMID- 30289850
TI  - Whole Exome Sequencing of Adult and Pediatric Cohorts of the Rare Vascular
      Disorder Systemic Capillary Leak Syndrome.
AB  - OBJECTIVE: Systemic capillary leak syndrome (SCLS) is a rare disorder that
      presents with episodes of hypovolemic shock. The extent to which genetic
      abnormalities contribute to SCLS is unknown. We identified pediatric and adult
      cohorts with characteristic clinical courses. We sought to describe the clinical
      characteristics of both cohorts, identify a possible genetic contribution to
      SCLS, and demonstrate that whole exome sequencing (WES) may be conducted by
      critical care providers. DESIGN: Prospective observational study of WES of nine
      adult and eight pediatric SCLS patients and available unaffected first-degree
      relatives. SETTING: Tertiary children's hospitals and referral research
      laboratory. PATIENTS: Children and adults with SCLS. INTERVENTIONS: None.
      MEASUREMENTS: Patients and available first-degree relatives underwent WES. Data
      were analyzed for rare homozygous, bi-allelic, de novo and heterozygous variants
      with allelic enrichment and metabolic pathway analyses. MAIN RESULTS: Children
      with SCLS presented at a younger age with episodes similar to those experienced
      by adults. All patients and available relatives underwent satisfactory WES. No
      overlapping gene variants or metabolic pathways were identified across all SCLS
      patients. Multiple candidate genes with homozygous or bi-allelic mutations were
      identified in individual subjects with SCLS. There was no significant enrichment
      of genes with rare heterozygous variants. CONCLUSIONS: The clinical
      characteristics of children and adults with SCLS are similar. We did not identify
      a uniform germline exomic genetic etiology for SCLS. WES identified several
      candidate genes in individual patients for future research. WES is a viable way
      for critical care providers to investigate the etiology of diseases with presumed
      genetic contributions.

PMID- 30289851
TI  - Early Differential Value of Plasma Presepsin on Infection of Trauma Patients.
AB  - OBJECTIVE: Early differential diagnosis of an infection in a trauma patient is
      likely to have a significant influence on the prognosis. In the present study, we
      evaluated the early differential value of plasma presepsin, procalcitonin (PCT),
      C-reactive protein (CRP), and white blood cells (WBCs) on infection in trauma
      patients. METHODS: Trauma patients were divided into noninfected (n = 89) and
      infected trauma groups (n = 68); healthy adult volunteers (n = 60) and patients
      having sterile surgery (n = 60) were enrolled as the controls. Plasma presepsin,
      PCT, CRP, and WBC counts were measured and the injury severity score (ISS) was
      calculated. RESULTS: Plasma presepsin levels within the first 3 d of admission
      were only significantly increased in the infected trauma group, but not in the
      noninfected trauma and sterile groups. This indicated that presepsin might have
      an ability to differentiate the infection in trauma patients; however, plasma
      PCT, CRP, and WBCs were significantly increased in both the infected and
      noninfected trauma patients. Binary logistic regression analysis showed that only
      increased plasma presepsin, PCT, and ISS were significantly associated with an
      increased likelihood of infection in trauma patients. Both presepsin and PCT were
      valuable for diagnosing infection; presepsin had a higher area under the curve
      than PCT. CONCLUSIONS: Presepsin might be a superior biomarker for early
      differentiation of infection in trauma patients; however, trauma stress elevates
      PCT, CRP, and WBCs even in the absence of infection; therefore, caution is
      advised when using these indicators to diagnose infection.

PMID- 30289852
TI  - Remote Intestinal Injury Early After Experimental Polytrauma and Hemorrhagic
      Shock.
AB  - Dysfunction of the gut-blood barrier plays an important role in many diseases,
      such as inflammatory bowel disease, hemorrhagic shock (HS) or burn injury.
      However, little is known about gut barrier dysfunction after hemodynamically
      instable polytrauma (PT). Therefore, we aimed to evaluate the effects of PT and
      HS on remote intestinal damage and barrier dysfunction, especially regarding the
      role of Zonula occludens protein 1 (ZO-1) as an important tight junction
      protein.Male C57BL/6 mice were subjected to either PT (thorax trauma, closed head
      injury, soft tissue injury and distal femoral fracture), 60 min of pressure
      controlled HS (30 +/- 5 mmHg), or PT+HS, or sham procedures.Animals of all trauma
      groups showed an increase in abdominal girth and dilation of the intestine during
      the experimental period, which was largest in the PT+HS group. Increased blood
      tissue permeability to albumin (assessed by Evans blue dye) was found in the HS
      group. Experimental groups showed a slight increase in plasma concentration of
      intestinal fatty acid binding protein and some intestinal damage was
      histologically detectable. Of note, PT+HS animals revealed significantly reduced
      expression of ZO-1 in intestinal epithelial cells. In an in vitro model,
      stimulation of human colon epithelial cells with peptidoglycan, but not with
      lipopolysaccharide, resulted in elevated secretion of proinflammatory cytokines,
      reflecting inflammatory activity of the intestinal epithelium.Taken together, PT
      and HS lead to increased permeability of the gut-blood barrier. Bacterial
      components may lead to production of inflammatory and chemotactic mediators by
      gut epithelial cells, underlining the role of the gut as an immunologically
      active organ.

PMID- 30289853
TI  - Distinct Dynamics of Stem and Progenitor Cells in Blood of Polytraumatized
      Patients.
AB  - Endogenously mobilized stem and progenitor cells (SPCs) or exogenously provided
      SPCs are thought to be beneficial for trauma therapy. However, still little is
      known about the synchronized dynamics of the number of SPCs in blood after severe
      injury and parameters like cytokine profiles that correlate with these numbers.
      We determined the number of hematopoietic stem cells, common myeloid progenitors,
      granulocyte-macrophage progenitors and mesenchymal stem/stromal cells in
      peripheral blood (PB) 0-3 h, 8 h, 24 h, 48 h and 120 h after polytrauma in
      individual patients (injury severity score >= 21). We found that the number of
      blood SPCs follow on average a synchronous, inverse bell-shaped distribution,
      with an increase at 0-3 h, followed by a strong decrease, with a nadir in SPC
      numbers in blood at 24 h or 48 h. The change in numbers of SPCs in PB between 48
      h and 120 h revealed two distinct patterns: Pattern 1 is characterized by an
      increase in the number of SPCs to a level higher than normal, pattern 2 is
      characterized by an almost absent increase in the number of SPCs compared to the
      nadir. Changes in the concentrations of the cytokines CK, MDC, IL-8, G-CSF Gro
      alpha, VEGF and MCP-1 correlated with changes in the number of SPCs in PB or were
      closely associated with Pattern 1 or Pattern 2. Our data provide novel rationale
      for investigations on the role of stem cell mobilization in polytraumatized
      patients and its likely positive impact on trauma outcome.

PMID- 30289854
TI  - Leadership Presence: A "Must" Skill for Impactful Case Manager-Client
      Relationship.
AB  - Successful case manager-client relationships are those that demonstrate a
      humanistic, personal, empathetic, and empowering approach to health care
      provision. This editorial discusses leadership presence as an essential skill for
      professional case management practice and the impact of such relationships on the
      client/support system experience of care. It also presents a framework for
      building impactful and therapeutic relationships. In addition, it offers a list
      of key strategies that contribute to the success of the professional case
      manager.

PMID- 30289855
TI  - The New Age of Bullying and Violence in Health Care: Part 4: Managing
      Organizational Cultures and Beyond.
AB  - : Disrespect among the health and behavioral health workforce may have reached
      the point of no return. The industry is on heightened alert, as the disruptive
      behaviors of bullying and lateral violence, plus escalating incidents of
      workforce harassment and workplace violence incidents, impact every practice
      setting. These behaviors contribute to concerns around client and professional
      safety, quality-of-care processes, as well as workforce retention and mental
      health. PURPOSE/OBJECTIVES: This article: PRIMARY PRACTICE SETTING(S)::
      Applicable to all health and behavioral health settings where case management is
      practiced. FINDINGS/CONCLUSIONS: Despite glaring improvements in how care is
      rendered and an enhanced focus on quality delivery of care, organizations must
      address cultures that support as opposed to negate disruptive workplace
      behaviors. The emerging regulatory and organizational initiatives to reframe the
      delivery of care will become meaningless without consistent attention to
      enforcement of regulatory, policy, and prevention actions. IMPLICATIONS FOR CASE
      MANAGEMENT PRACTICE: Professionals who hesitate to confront and address incidents
      of disruptive and oppressive behavior in the health care workplace potentially
      practice unethically. Bullying has fostered a dangerous culture of silence in the
      industry, one which impacts client safety, quality care delivery, plus has longer
      term behavioral health implications for the professionals striving to render
      care. Add the escalating numbers specific to workplace violence and the trends
      speak to an atmosphere of safety and quality in the health care workplace that
      puts clients and professionals at risk.

PMID- 30289856
TI  - The New Age of Bullying and Violence in Health Care: Part 4: Managing
      Organizational Cultures and Beyond.

PMID- 30289857
TI  - The Best Practice for Increasing Telephone Outreach: An Integrative Review.
AB  - PURPOSE OF STUDY: Many hospitals established telephone follow-up (TFU) programs
      to improve care transitions and reduce hospital readmissions. However, there is a
      lack of knowledge on how to increase the outreach of TFU programs. This
      integrative review aims to answer the clinical practice question, "What is the
      best practice for increasing telephone follow-up reach rates post-hospital
      discharge?" PRIMARY PRACTICE SETTING: The primary setting evaluated in this
      review was hospital-based phone call programs that are conducting post-hospital
      discharge TFU. METHODOLOGY: In this integrative review, we searched studies
      published between January 2003 and November 2017. We searched 5 electronic
      databases including PubMed, EMBASE, CINAHL, Web of Science, and Cochrane. The
      Johns Hopkins Nursing Evidence-Based Practice model was used to critically
      analyze and synthesize the selected articles. RESULTS: Nine articles were
      reviewed, and this study uncovered that pre-hospital face-to-face meeting might
      increase TFU reach rates. However, most studies calculated reach rates using only
      frequencies/percentages. This contributed to our low-quality rating on most of
      the reviewed studies. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: This review
      identified that TFU, as a component of a care coordination program, may reduce
      hospital readmissions and control health care utilization. However, few studies
      (n = 2) used TFU reach rates as a major study outcome to determine the impact of
      face-to-face meetings on phone outreach. Therefore, the evidence is limited to
      inform case management practice to increase phone outreach post-hospital
      discharge. It is recommended to conduct further research and test different
      methods that may increase phone outreach.

PMID- 30289858
TI  - The Best Practice for Increasing Telephone Outreach: An Integrative Review.

PMID- 30289860
TI  - Evaluation of a Hospital: Community Partnership to Reduce 30-Day Readmissions.
AB  - PURPOSE: To evaluate the ComPass program by (1) effectiveness in reducing 30-day
      hospital readmissions, (2) reach of program into target population, and (3)
      implementation of key program elements. PRIMARY PRACTICE SETTING: An academic
      hospital in New England (John Dempsey Hospital). METHODOLOGY AND SAMPLE:
      Retrospective analysis of Medicare fee-for-service (FFS) beneficiaries
      hospitalized at John Dempsey Hospital between May 1, 2012, and November 30, 2014.
      RESULTS: The program reached 34% of eligible Medicare FFS beneficiaries (n = 832;
      61% female, mean age = 79 years). The unadjusted 30-day all-cause readmission
      rate decreased from 21% to 16.2% (p = .03). Implementation was high for
      postdischarge phone calls (89%) but low for home visits (34%). The mean change in
      patient activation scores following completion of the program was 0.15 (SD =
      4.79), with no change in patient activation level, chi (6) = 3.82, p = .70.
      IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: The ComPass program was consistent
      with the philosophy and standards of case management practice. Case managers will
      want to utilize an evidence-based instrument with real-time information to
      identify patients at risk for 30-day readmission. A physical presence of ComPass
      coaches within the hospital enabled a strong hospital-community-based
      organization (CBO) partnership, facilitating the coordination, communication, and
      collaboration. Case managers will want to advocate for policy incentivizing
      hospital-CBO partnerships. Patient activation is essential; case managers may
      benefit from training in motivational interviewing to improve patient activation
      and outcomes. Additional research is needed to further elucidate and mitigate
      barriers to posttransition home visits and patient activation.

PMID- 30289861
TI  - Under the Case Management Practice "Umbrella": CMSA's Standards and CCMC's Code
      of Conduct.

PMID- 30289859
TI  - Improving Functional Assessment in Older Adults Transitioning From Hospital to
      Home.
AB  - PURPOSE/OBJECTIVES: The purpose of this article is to highlight how scientists
      have assessed all components of functional status in older adults transitioning
      from hospital to home to date, discuss ways of improving assessment of functional
      status, and discuss implications for case management research and practice.
      PRIMARY PRACTICE SETTING(S): This article focuses on case management of older
      adults transitioning from hospital to home. FINDINGS/CONCLUSIONS: There any many
      ways to assess functional status, including basic activities of daily living
      (BADL), instrumental activities of daily living (IADL), and other nonphysical
      domains of function such as leisure, social, and productive activities. However,
      assessment of function in older adults transitioning from hospital to home is
      primarily limited to BADL. Nonphysical domains of functional status have been
      linked to important outcomes in community-dwelling older adults and could give
      clinicians and researchers a better understanding of how older adults are
      functioning, as well as allow for earlier recognition of those who are beginning
      to experience functional decline. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: In
      case management, it is important to ask older adults about goals regarding their
      functional status and how they think about their functioning in the hospital and
      at home. Early identification of older adults' functional goals while in the
      hospital is the first step toward regaining their ideal or premorbid function
      after discharge to home. To best determine baseline functional status, we may
      need to consider assessments that can measure multiple domains of functioning in
      older adults, such as the Sickness Impact Profile. Gaining a more comprehensive
      understanding and assessment of functional status for hospitalized older adults
      would help inform discharge destinations and improve transitions in care.

PMID- 30289862
TI  - Signing Off...

PMID- 30289863
TI  - Texting and Case Management.

PMID- 30289864
TI  - Public Policy in Action: Advocating for Case Management Practice.

PMID- 30289865
TI  - Online Education and Case Management.

PMID- 30289866
TI  - Relationship Between Heart Rate Variability and Acute: Chronic Load Ratio
      Throughout a Season in NCAA D1 Men's Soccer Players.
AB  - Sekiguchi, Y, Huggins, RA, Curtis, RM, Benjamin, CL, Adams, WM, Looney, DP, West,
      CA, and Casa, DJ. Relationship between heart rate variability and acute:chronic
      load ratio throughout a season in NCAA D1 men's soccer players. J Strength Cond
      Res XX(X): 000-000, 2018-The purpose of this study was twofold: (a) to examine
      the relationship between heart rate variability (HRV) and acute:chronic workload
      ratio (ACWR)-based training load (TL) metrics and (b) to examine relationships
      across various A:C ratio-based TL metrics. Heart rate variability in 23 male
      college soccer players (mean +/- SD; age, 21 +/- 1 years; body mass, 80.3 +/- 5.8
      kg; height, 181.9 +/- 6.5 cm; %body fat, 11.9 +/- 2.0%; and V[Combining Dot
      Above]O2max, 51.9 +/- 5.0 ml.kg.min) was measured at 5 time points: week(W)1, W3,
      W7, W12, and W14 during the 2015 NCAA men's soccer season. Heart rate variability
      was calculated from beat to beat intervals using a heart rate monitor. Players
      donned a global position satellite-enabled device that measured the following TL
      metrics: session time (ST), Player Load (PL), PL.min, and total distance (TD).
      Acute:chronic workload ratio was calculated for each TL metric: ACWR-based ST
      (ACWRST), ACWR-based PL (ACWRPL), ACWR-based PL.min (ACWRPLM), and ACWR-based TD
      (ACWRTD): ACWR = week average TLs/mo average (30 +/- 1 days) TLs. Relationships
      between HRV and ACWR-based each TL metric were evaluated using mixed effects
      models. Tukey pairwise comparisons were used to examine differences between types
      of ACWR-based TL metrics. An increase in ACWRST significantly reduced HRV
      throughout a season (-7.4 +/- 3.6 m.s; p = 0.04). There were significant
      differences between ACWRPLM and ACWRST, ACWRPL and ACWRTD at W1, ACWRPLM and
      ACWRST at W3 (p < 0.05). In conclusion, ACWRST, ACWRPL, and ACWRTD were
      significantly different from ACWRPLM. ACWRST was found to significantly predict
      HRV; higher ACWRST was significantly associated with lower HRV. Therefore,
      tracking of the ACWR using ST may help to optimize athlete's physiological state
      throughout a season.

PMID- 30289867
TI  - Complexity of Knee Extensor Torque: Effect of Aging and Contraction Intensity.
AB  - Fiogbe, E, Vassimon-Barroso, V, Catai, AM, de Melo, RC, Quiterio, RJ, Porta, A,
      and Takahashi, ACdM. Complexity of knee extensor torque: effect of aging and
      contraction intensity. J Strength Cond Res XX(X): 000-000, 2018-Assessing the
      knee extensors' torque complexity in old adults is relevant because these muscles
      are among the most involved in functional daily activities. This study aimed to
      investigate the effects of aging and isometric contraction intensity on knee
      extensor torque complexity. Eight young (24 +/- 2.8 years) and 13 old adults (63
      +/- 2.8 years) performed 3 maximal (maximum voluntary contraction [MVC], duration
      = 10 seconds) and submaximal isometric contractions (SICs, targeted at 15, 30,
      and 40% of MVC, respectively) of knee extensors. Torque signals were sampled
      continuously, and the metrics of variability and complexity were calculated
      basing on the SIC torque data. The coefficient of variation (CV) was used to
      quantify the torque variability. The torque complexity was determined by
      calculating the corrected approximate entropy (CApEn) and sample entropy (SampEn)
      and its normalized versions (NCApEn and NSampEn). Young subjects produced greater
      isometric torque than old adults, and the CV was similar between both groups
      except at the highest force level (40% MVC) where young subjects' value was
      higher. The major novel finding of this investigation was that although the knee
      extensor torque complexity is reduced in old adults, its relationship with
      contraction intensity is similar to young subjects. This means that despite the
      age-related decrease of the interactions between the components of the
      neuromuscular system, the organization of force control remains preserved in old
      adults, at least up to just below the force midrange.

PMID- 30289868
TI  - Pacing Profiles of Olympic and IAAF World Championship Long-Distance Runners.
AB  - Filipas, L, La Torre, A, and Hanley, B. Pacing profiles of Olympic and
      International Association of Athletics Federations World Championship long
      distance runners. J Strength Cond Res XX(X): 000-000, 2018-The aim of this study
      was to analyze the pacing profiles of Olympic and International Association of
      Athletics Federations (IAAF) World Championship long-distance finalists,
      including the relationship with their recent best times. The times for each 1,000
      m split were obtained for 394 men and women in 5,000- and 10,000-m finals at 5
      championships. Athletes' best times from the previous 32 months were also
      obtained. Similar pacing profiles were used by athletes grouped by finishing
      position in 5,000-m races. Women adopted a more even pacing behavior,
      highlighting a possible sex-based difference over this distance. Pacing behavior
      over 10,000 m was more similar between men and women compared with over 5,000 m.
      The main difference between men and women was that in the men's 10,000 m, as in
      the men's 5,000 m, more athletes were able to follow the leading group until the
      final stages. There were large or very large correlations between athletes' best
      times from the previous 32 months and their result; the fastest finishers also
      ran closer to their previous 32 months' best times. Despite differences in pacing
      behavior between events, long-distance runners should nonetheless stay close to
      the front from the beginning to win a medal.

PMID- 30289869
TI  - Individualizing Acceleration in English Premier League Academy Soccer Players.
AB  - Abbott, W, Brickley, G, Smeeton, NJ, and Mills, S. Individualizing acceleration
      in English Premier League academy soccer players. J Strength Cond Res 32(12):
      3512-3519, 2018-Global thresholds are typically used to band acceleration
      dependent on intensity. However, global thresholds do not account for variation
      in individual capacities, failing to quantify true intensity of acceleration.
      Previous research has investigated discrepancies in high-speed distance produced
      using global and individual speed thresholds, not yet investigated for
      acceleration. The current aim was to investigate discrepancies between global and
      individual thresholds when quantifying acceleration tasks. Acceleration data were
      recorded for 31 professional soccer players, using 10-Hz global positioning
      systems devices. Distances traveled performing low-, moderate-, and high
      intensity acceleration were calculated for athletes using global and individual
      thresholds. Global acceleration thresholds for low-, moderate-, and high
      intensity acceleration were classified as 1-2, 2-3, and >3 m.s, respectively,
      with individual thresholds classified as 25-50%, 50-75%, and >75% of maximum
      acceleration, respectively. Athletes were grouped low (LO), medium (ME), or high
      (HI) maximum accelerative capacity, determined using 3 maximal 40-m linear
      sprints. Two-way mixed-design analyses of variance were used to analyze
      differences in acceleration distances produced between analysis methods and
      athlete groups. No significant differences were identified between analysis
      methods for LO. For ME, no significant differences were demonstrated for low
      intensity. Moderate- and high-intensity acceleration distances were significantly
      higher for global compared with individual analysis method (p < 0.01). For HI,
      significantly higher acceleration distances were produced for all acceleration
      intensities using global thresholds (p < 0.01). Significant differences
      identified between analysis methods suggest practitioners must apply caution when
      using global thresholds. Global thresholds do not account for individual
      capacities and may provide an inaccurate representation of relative intensity of
      acceleration tasks.

PMID- 30289870
TI  - Show Me, Tell Me, Encourage Me: The Effect of Different Forms of Feedback on
      Resistance Training Performance.
AB  - Weakley, J, Wilson, K, Till, K, Banyard, H, Dyson, J, Phibbs, P, Read, D, and
      Jones, B. Show me, tell me, encourage me: The effect of different forms of
      feedback on resistance training performance. J Strength Cond Res XX(X): 000-000,
      2018-When performing resistance training, verbal kinematic feedback and visual
      kinematic feedback are known to enhance performance. In addition, providing
      verbal encouragement can assist in the attenuation of fatigue. However, the
      effects of these forms of feedback have never been compared. Consequently, this
      study aimed to quantify the effects of verbal kinematic feedback and visual
      kinematic feedback, and verbal encouragement on barbell velocity during the back
      squat. Furthermore, changes in performance were related to individual-reported
      conscientiousness. Twelve semiprofessional rugby union players volunteered to
      participate in the study that consisted of the subjects completing a set of the
      barbell back squat across 4 conditions (i.e., no-feedback [control], verbal
      feedback of kinematic information [verbal], visual feedback of kinematic
      information [visual], and verbal encouragement [encouragement]). In addition,
      participants completed a questionnaire before the study to assess
      conscientiousness. Magnitude-based inferences were used to assess differences
      between conditions, whereas Spearman's rank correlation coefficient was used to
      assess relationships between conscientiousness and changes in barbell velocity.
      All 3 forms of feedback showed almost certain improvements in barbell velocity,
      while differences between interventions were likely to very likely trivial.
      Changes in barbell velocity showed small to large inverse relationships with
      conscientiousness. These findings suggest that practitioners should supply
      kinematic feedback (verbally or visually) or, when technology is not available,
      provide athletes with encouraging statements while resistance training. Verbal
      encouragement may be of greatest benefit for individuals who demonstrate low
      levels of conscientiousness. Given these findings, practitioners are advised to
      use either technology or verbal encouragement to manipulate acute training
      outcomes.

PMID- 30289871
TI  - Sleep Profiles of Elite Swimmers During Different Training Phases.
AB  - Walsh, JA, Sanders, D, Hamilton, DL, and Walshe, I. Sleep profiles of elite
      swimmers during different training phases. J Strength Cond Res XX(X): 000-000,
      2018-This study aims to describe the sleeping patterns during different training
      phases in competitive swimmers. Twelve national- and international-level swimmers
      (3 females and 9 males) were monitored during 4 different phases, consisting of a
      preparation training phase, a taper phase, a competition phase, and a rest phase.
      Sleep parameters were assessed using wrist activity monitors and self-reported
      sleep diaries. There was a moderately higher (d = 0.70-1.00) sleep onset latency
      during the competition phase compared with taper, train, and rest phases. Trivial
      to small differences were observed for total sleep time between phases (d = 0.05
      0.40). Sleep efficiency was moderately higher (d = 0.60-0.75) in the training and
      taper phases compared with competition and rest. Restfulness and fragmentation
      index (FI) were lowest in the rest with differences between phases being small (d
      = 0.43-0.51) for restfulness and small to moderate (d = 0.43-0.62) for FI. Time
      in and out of bed was very largely later (d = 1.96-2.34) in rest compared with
      the other phases. Total nap time was moderately lower in rest (d = 1.13-1.18)
      compared with the training and competition phases, whereas there was a small
      difference (d = 0.46) compared with taper. To conclude, while there were trivial
      to small differences in sleep quantity between phases, there are small to
      moderate differences in other sleep parameters. Specifically, sleep onset latency
      was higher during the competition phase. In addition, this study highlights the
      substantial between-individual variations in sleep responses during different
      training phases.

PMID- 30289872
TI  - Individual Muscle Hypertrophy and Strength Responses to High vs. Low Resistance
      Training Frequencies.
AB  - Damas, F, Barcelos, C, Nobrega, SR, Ugrinowitsch, C, Lixandrao, ME, Santos, LMEd,
      Conceicao, MS, Vechin, FC, and Libardi, CA. Individual muscle hypertrophy and
      strength responses to high vs. low resistance training frequencies. J Strength
      Cond Res XX(X): 000-000, 2018-The aim of this short communication was to compare
      the individual muscle mass and strength gains with high (HF) vs. low (LF)
      resistance training (RT) frequencies using data from our previous study. We used
      a within-subject design in which 20 subjects had one leg randomly assigned to HF
      (5* per week) and the other to LF (2 or 3* per week). Muscle cross-sectional area
      and 1 repetition maximum were assessed at baseline and after 8 weeks of RT. HF
      showed a higher 8-week accumulated total training volume (TTV) (p < 0.0001)
      compared with LF. Muscle cross-sectional area and 1 repetition maximum values
      increased significantly and similarly for HF and LF protocols (p > 0.05). This
      short communication highlights that some individuals showed greater muscle mass
      and strength gains after HF (31.6 and 26.3% of individuals, respectively), other
      had greater gains with LF (36.8 and 15.8% of individuals, respectively), and even
      others showed similar responses between HF and LF, regardless of the consequent
      higher or lower TTV resulted from HF and LF, respectively. Importantly,
      individual manipulation of RT frequency can improve the intrasubject
      responsiveness to training, but the effect is limited to each individual's
      capacity to respond to RT. Finally, individual response to different frequencies
      and resulted TTV does not necessarily agree between muscle hypertrophy and
      strength gains.

PMID- 30289873
TI  - Examination of Physical Fitness Parameters Between Professional and Amateur Greek
      Soccer Players During the Transition Period.
AB  - Bekris, E, Pidoulas, G, Pidoulas, P, Gissis, I, Katis, A, and Komsis, S.
      Examination of physical fitness parameters between professional and amateur Greek
      soccer players during the transition period. J Strength Cond Res XX(X): 000-000,
      2018-The aim of the study was to compare physical fitness parameters between
      professional and amateur soccer players of different levels. The sample consisted
      of 381 soccer players divided in 4 experimental groups: first division
      professional players (n = 115), second division professional players (n = 70),
      third division semiprofessional players (n = 93), and amateur soccer players (n =
      103). Players were tested for several physiological parameters at the end of the
      transition period. Analysis of variance showed significantly lower body fat and
      increased maximum oxygen consumption (V[Combining Dot Above]O2max) and velocity
      of maximum oxygen consumption (vV[Combining Dot Above]O2max) values for first
      division professional players compared with the other experimental groups (p <
      0.05). Similarly, first division professional players showed higher performance
      during squat jump and countermovement jump test compared with the other
      experimental groups (p < 0.05). Significant differences on flexibility test were
      observed between amateur players and the other group (p < 0.05). The results of
      the study indicated that Greek soccer players at the highest level overcome in
      almost all the underexamination physiological parameters probably because of less
      absence from training and better implementation of training programs during the
      transition period.

PMID- 30289874
TI  - Optimizing Between-Session Reliability for Quadriceps Peak Torque and Rate of
      Torque Development Measures.
AB  - Grindstaff, TL, Palimenio, MR, Franco, M, Anderson, D, Bagwell, JJ, and
      Katsavelis, D. Optimizing between-session reliability for quadriceps peak torque
      and rate of torque development measures. J Strength Cond Res XX(X): 000-000, 2018
      Quadriceps peak torque and rate of torque development (RTD) have relevance for
      athletic performance and recovery after knee injury. The number of repetitions
      performed to determine RTD varies between studies, and the associated measurement
      error has not been established. The purpose of this study was to determine the
      number of repetitions necessary to optimize the between-session reliability for
      isometric quadriceps peak torque and RTD measures and to quantify estimates of
      measurement error. Twenty participants (age = 21.7 +/- 1.7 years, height = 172.5
      +/- 16.0 cm, body mass = 76.0 +/- 15.5 kg, and Tegner = 7.1 +/- 1.2) volunteered
      for this study. Quadriceps isometric peak torque and RTD (50, 100, 150, 200, and
      250 ms, and maximum torque) were obtained during 2 testing sessions. Between
      session reliability was determined using intraclass correlation coefficients
      (ICC2,k), using the minimal detectable change (MDC) and coefficient of variation
      (CoV) to quantify measurement error. Between-session reliability was best
      maximized by using the average of the 3 repetitions with the highest peak torque.
      Reliability was good for quadriceps peak torque (ICC2,3 = 0.98; MDC = 51.1 N.m;
      CoV = 38.0%) and ranged from moderate to good for quadriceps RTD measures (ICC2,3
      = 0.61 to 0.91; MDC = 264.8 to 738.3 N.m.s; CoV = 38.1-57.9%). Measures of late
      RTD were less variable and more reliable than early RTD and average RTD measures.
      These results provide confidence when measuring between-session changes for late
      RTD measures, but changes in early RTD may be more difficult to distinguish from
      measurement error. Methods should be used to minimize variability between
      repetitions and sessions.

PMID- 30289875
TI  - Identification of Key Genes and Pathways Associated with RUNX1 Mutations in Acute
      Myeloid Leukemia Using Bioinformatics Analysis.
AB  - BACKGROUND RUNXl plays a key regulatory role in the process of hematopoiesis and
      is a common target for multiple chromosomal translocations in human acute
      leukemia. Mutations of RUNX1 gene can lead to acute leukemia and affect the
      prognosis of AML patients. We aimed to identify pivotal genes and pathways
      involved in RUNX1-mutated patients of with acute myeloid leukemia (AML) and to
      explore possible molecular markers for novel therapeutic targets of the disease.
      MATERIAL AND METHODS The RNA sequencing datasets of 151 cases of AML were
      obtained from the Cancer Genome Atlas database. Differentially expressed genes
      (DEGs) were identified using edgeR of the R platform. PPI (protein-protein
      interaction) network clustering modules were analyzed with ClusterONE, and the
      KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses for
      modules were performed. RESULTS A total of 379 genes were identified as DEGs. The
      KEGG enrichment analysis of DEGs showed significantly enriched pathways in
      cancer, extracellular matrix (ECM)-receptor interaction pathway, and cyclic
      adenosine monophosphate (cAMP) signaling pathway. The top 10 genes ranked by
      degree were PRKACG, ANKRD7, RNFL7, ROPN11, TEX14, PRMT8, OTOA, CFAP99, NRXN1, and
      DMRT1, which were identified as hub genes from the protein-protein interaction
      network (PPI). Statistical analysis revealed that RUNX1-mutated patients with AML
      had a shorter median survival time (MST) with poor clinical outcome and an
      increased risk of death when compared with those without RUNX1 mutations.
      CONCLUSIONS DEGs and pathways identified in the present study will help
      understand the molecular mechanisms underlying RUNX1 mutations in AML and develop
      effective therapeutic strategies for RUNX1-mutation AML.

PMID- 30289876
TI  - Crafting your scientist brand.
AB  - That a scientist might shape and cultivate a personal brand is a relatively new
      concept but one that is finding increasing acceptance in this new age of rapid
      communications and social media. A key driver is the abrupt rise in well-funded
      and organized antiscience movements, especially in North America and Europe, such
      that society now benefits from scientists with strong personal brands and public
      personas who are willing to engage general audiences. In this sense, branding
      itself can advance science, the sharing of information, and the promotion of
      science as a public good. Still another dimension to branding is that it affords
      an opportunity to mentor younger scientists and helps you to become an important
      role model for the next generation. There is also a practical side, as today,
      fewer scientists spend their entire career at a single institution, so owning a
      strong brand can sometimes create easier paths for transitions and mobility.
      However, brand cultivation ideally begins in collaboration with your
      institutional office of communications and is done in a way that is seen as a win
      for both you and your university or research institution. Described here are some
      steps to consider when embarking on brand cultivation and how to avoid some of
      the potential pitfalls.

PMID- 30289877
TI  - Functional conservation of sequence determinants at rapidly evolving regulatory
      regions across mammals.
AB  - Recent advances in epigenomics have made it possible to map genome-wide
      regulatory regions using empirical methods. Subsequent comparative epigenomic
      studies have revealed that regulatory regions diverge rapidly between genome of
      different species, and that the divergence is more pronounced in enhancers than
      in promoters. To understand genomic changes underlying these patterns, we
      investigated if we can identify specific sequence fragments that are over
      enriched in regulatory regions, thus potentially contributing to regulatory
      functions of such regions. Here we report numerous sequence fragments that are
      statistically over-enriched in enhancers and promoters of different mammals
      (which we refer to as 'sequence determinants'). Interestingly, the degree of
      statistical enrichment, which presumably is associated with the degree of
      regulatory impacts of the specific sequence determinant, was significantly higher
      for promoter sequence determinants than enhancer sequence determinants. We
      further used a machine learning method to construct prediction models using
      sequence determinants. Remarkably, prediction models constructed from one species
      could be used to predict regulatory regions of other species with high accuracy.
      This observation indicates that even though the precise locations of regulatory
      regions diverge rapidly during evolution, the functional potential of sequence
      determinants underlying regulatory sequences may be conserved between species.

PMID- 30289879
TI  - Noise propagation in an integrated model of bacterial gene expression and growth.
AB  - In bacterial cells, gene expression, metabolism, and growth are highly
      interdependent and tightly coordinated. As a result, stochastic fluctuations in
      expression levels and instantaneous growth rate show intricate cross
      correlations. These correlations are shaped by feedback loops, trade-offs and
      constraints acting at the cellular level; therefore a quantitative understanding
      requires an integrated approach. To that end, we here present a mathematical
      model describing a cell that contains multiple proteins that are each expressed
      stochastically and jointly limit the growth rate. Conversely, metabolism and
      growth affect protein synthesis and dilution. Thus, expression noise originating
      in one gene propagates to metabolism, growth, and the expression of all other
      genes. Nevertheless, under a small-noise approximation many statistical
      quantities can be calculated analytically. We identify several routes of noise
      propagation, illustrate their origins and scaling, and establish important
      connections between noise propagation and the field of metabolic control
      analysis. We then present a many-protein model containing >1000 proteins
      parameterized by previously measured abundance data and demonstrate that the
      predicted cross-correlations between gene expression and growth rate are in broad
      agreement with published measurements.

PMID- 30289878
TI  - Human genetic variation in GLS2 is associated with development of complicated
      Staphylococcus aureus bacteremia.
AB  - The role of host genetic variation in the development of complicated
      Staphylococcus aureus bacteremia (SAB) is poorly understood. We used whole exome
      sequencing (WES) to examine the cumulative effect of coding variants in each gene
      on risk of complicated SAB in a discovery sample of 168 SAB cases (84 complicated
      and 84 uncomplicated, frequency matched by age, sex, and bacterial clonal complex
      [CC]), and then evaluated the most significantly associated genes in a
      replication sample of 240 SAB cases (122 complicated and 118 uncomplicated,
      frequency matched for age, sex, and CC) using targeted sequence capture. In the
      discovery sample, gene-based analysis using the SKAT-O program identified 334
      genes associated with complicated SAB at p<3.5 x 10-3. These, along with eight
      biologically relevant candidate genes were examined in the replication sample.
      Gene-based analysis of the 342 genes in the replication sample using SKAT-O
      identified one gene, GLS2, significantly associated with complicated SAB (p = 1.2
      x 10-4) after Bonferroni correction. In Firth-bias corrected logistic regression
      analysis of individual variants, the strongest association across all 10,931
      variants in the replication sample was with rs2657878 in GLS2 (p = 5 x 10-4).
      This variant is strongly correlated with a missense variant (rs2657879, p = 4.4 x
      10-3) in which the minor allele (associated here with complicated SAB) has been
      previously associated with lower plasma concentration of glutamine. In a
      microarray-based gene-expression analysis, individuals with SAB exhibited
      significantly lower expression levels of GLS2 than healthy controls. Similarly,
      Gls2 expression is lower in response to S. aureus exposure in mouse RAW 264.7
      macrophage cells. Compared to wild-type cells, RAW 264.7 cells with Gls2 silenced
      by CRISPR-Cas9 genome editing have decreased IL1-beta transcription and increased
      nitric oxide production after S. aureus exposure. GLS2 is an interesting
      candidate gene for complicated SAB due to its role in regulating glutamine
      metabolism, a key factor in leukocyte activation.

PMID- 30289880
TI  - Heritability informed power optimization (HIPO) leads to enhanced detection of
      genetic associations across multiple traits.
AB  - Genome-wide association studies have shown that pleiotropy is a common phenomenon
      that can potentially be exploited for enhanced detection of susceptibility loci.
      We propose heritability informed power optimization (HIPO) for conducting
      powerful pleiotropic analysis using summary-level association statistics. We find
      optimal linear combinations of association coefficients across traits that are
      expected to maximize non-centrality parameter for the underlying test statistics,
      taking into account estimates of heritability, sample size variations and
      overlaps across the traits. Simulation studies show that the proposed method has
      correct type I error, robust to population stratification and leads to desired
      genome-wide enrichment of association signals. Application of the proposed method
      to publicly available data for three groups of genetically related traits, lipids
      (N = 188,577), psychiatric diseases (Ncase = 33,332, Ncontrol = 27,888) and
      social science traits (N ranging between 161,460 to 298,420 across individual
      traits) increased the number of genome-wide significant loci by 12%, 200% and
      50%, respectively, compared to those found by analysis of individual traits.
      Evidence of replication is present for many of these loci in subsequent larger
      studies for individual traits. HIPO can potentially be extended to high
      dimensional phenotypes as a way of dimension reduction to maximize power for
      subsequent genetic association testing.

PMID- 30289882
TI  - Influence of femoral broach shape on stem alignment using anterior approach for
      total hip arthroplasty: A radiologic comparative study of 3 different stems.
AB  - BACKGROUND: Malalignment of the femoral stem in total hip arthroplasty (THA) can
      detrimentally affect outcome. Poor preparation of the femur intraoperatively is
      an important cause of stem malalignment. PURPOSES: The objective was to compare
      coronal alignment of three different stems using three different broaches.
      METHODS: Retrospective study of three groups of 60 patients following primary THA
      via direct anterior approach, by the same surgeon, between January 2015 and
      January 2016. Each group had a similar designed stem (Corail Depuy, Targos Lepine
      or Meije Tornier). Groups were matched for age, body mass index, gender, side,
      neck shaft angle and indications. The significant difference between groups was
      the broach shape. Broaches for the Corail and Meije stems had a prominent
      shoulder laterally, while the broach of the Targos stem had a rounded less
      prominent shape laterally. Coronal alignment was determined radiologically at 2
      months. RESULTS: The mean varus was significantly lower for the Targos stems (1.1
      degrees  +/-0.8) compared to the Corail (2.3 degrees  +/-1.5) and Meije stems
      (1.9 degrees  +/-1.2) (p<0.0001). There were significantly less Targos stems with
      varus greater than 3 degrees  (1.7%, n = 1) compared to the Corail (40%, n = 24)
      and Meije stems (20%, n = 12) (p<0.001). CONCLUSION: A femoral broach with a
      prominent lateral shoulder when performing a THA via direct anterior approach
      will increase the risk of varus femoral stem alignment compared to a less
      laterally prominent broach.

PMID- 30289881
TI  - In vitro and ex-vivo evaluation of topical formulations designed to minimize
      transdermal absorption of Vitamin K1.
AB  - Topical application of Vitamin K1 has been demonstrated to effectively treat
      papulopustular skin rash, a serious and frequently encountered side effect of
      Epidermal Growth Factor Inhibitors (EGFRIs). Systemic absorption of vitamin K1
      from skin and the resultant consequence of antagonizing EGFRIs anticancer effects
      jeopardizes the clinical acceptability of this rather effective treatment. The
      purpose of the present study was to rationally formulate and evaluate the release
      rate and transdermal absorption of a wide range of Vitamin K1 dermal preparations
      with a variety of physiochemical properties. A library of 33 formulations with
      were compounded and tested for Vitamin K1 permeation using hydrophobic membranes
      and porcine skin mounted in a Fran diffusion cells. Our results demonstrate the
      lowest diffusion for water-in-oil emulsions, which also demonstrated a negligible
      transdermal absorption. The statistical analysis showed a significant correlation
      between in vitro and ex vivo results. While viscosity did not have a significant
      impact on the diffusion or absorption of vitamin K1, an increase in the lipid
      content was correlated with an increase in transmembrane diffusion (not with
      transdermal absorption). Overall, formulation design significantly impacts the
      release rate and transdermal absorption of vitamin K1, and confirms the
      possibility of minimal systemic distribution of this vitamin for this specific
      purpose.

PMID- 30289883
TI  - Suppression of droplets freezing on glass surfaces on which antifreeze
      polypeptides are adhered by a silane coupling agent.
AB  - The development of ice-phobic, glass-substrate surfaces is important for many
      reasons such as poor visibility through the ice-covered windshields of vehicles.
      The present authors have developed new glass surfaces coated with a silane
      coupling agent and polypeptides whose amino-acid sequence is identical to a
      partial sequence of winter flounder antifreeze protein. We have conducted
      experiments on the freezing of sessile water droplets on the glass surfaces, and
      measured the droplet temperature, contact angle, contact area and surface
      roughness. The results show that the supercooling temperature decreased
      noticeably in the case where a higher concentration solution of polypeptide was
      used for the coating. The adhesion strength of frozen droplets was lowest in the
      same case. In addition, we observed many nanoscale humps on the coated surface,
      which were formed by polypeptide aggregates in the solution. We argue that the
      combination of the hydrophilic humps and the hydrophobic base surfaces causes
      water molecules adjacent to the surfaces to have a variety of orientations in
      that plane, even after the ice layer started to grow. This then induces a misfit
      of water-molecule spacing in the ice layers and consequent formation of fragile
      polycrystalline structure. This explains the lower values of ice adhesion
      strength and supercooling enhancement in the cases of the polypeptide-coated
      glass plates.

PMID- 30289884
TI  - Effects of a brief video intervention on treatment initiation and adherence among
      patients attending human immunodeficiency virus treatment clinics.
AB  - BACKGROUND: Persons with human immunodeficiency virus (HIV) who get and keep a
      suppressed viral load are unlikely to transmit HIV. Simple, practical
      interventions to help achieve HIV viral suppression that are easy and inexpensive
      to administer in clinical settings are needed. We evaluated whether a brief video
      containing HIV-related health messages targeted to all patients in the waiting
      room improved treatment initiation, medication adherence, and retention in care.
      METHODS AND FINDINGS: In a quasi-experimental trial all patients (N = 2,023)
      attending two HIV clinics from June 2016 to March 2017 were exposed to a theory
      based, 29-minute video depicting persons overcoming barriers to starting
      treatment, taking medication as prescribed, and keeping medical appointments. New
      prescriptions at index visit, HIV viral load test results, and dates of return
      visits were collected through review of medical records for all patients during
      the 10 months that the video was shown. Those data were compared with the same
      variables collected for all patients (N = 1,979) visiting the clinics during the
      prior 10 months (August 2015 to May 2016). Among patients exposed to the video,
      there was an overall 10.4 percentage point increase in patients prescribed
      treatment (60.3% to 70.7%, p< 0.01). Additionally, there was an overall 6.0
      percentage point improvement in viral suppression (56.7% to 62.7%, p< 0.01),
      however mixed results between sites was observed. There was not a significant
      change in rates of return visits (77.5% to 78.8%). A study limitation is that,
      due to the lack of randomization, the findings may be subject to bias and secular
      trends. CONCLUSIONS: Showing a brief treatment-focused video in HIV clinic
      waiting rooms can be effective at improving treatment initiation and may help
      patients achieve viral suppression. This feasible, low resource-reliant video
      intervention may be appropriate for adoption by other clinics treating persons
      with HIV. TRIAL REGISTRATION: http://www.ClinicalTrials.gov (NCT03508310).

PMID- 30289885
TI  - Identification of metabolite and protein explanatory variables governing
      microbiome establishment and re-establishment within a cellulose-degrading
      anaerobic bioreactor.
AB  - Proteins, metabolites, and 16S rRNA measurements were used to examine the
      community structure and functional relationships within a cellulose degrading
      anaerobic bioreactor. The bioreactor was seeded with bovine rumen fluid and
      operated with a 4 day hydraulic retention time on cellulose (avicel) as sole
      carbon and energy source. The reactor performance and microbial community
      structure was monitored during the establishment of the cellulose-degrading
      community. After stable operation was established in the bioreactor, the mixing
      intensity was increased in order to investigate the effect of a physical
      disruption of the microbial community structure. Finally, the original conditions
      were re-established to understand the stability of the microbial community after
      a perturbation. All factors measured were found to be inter-correlated during
      these three distinct phases of operation (establishment, perturbation and re
      establishment). In particular, the return of community structure and function to
      pre-perturbed conditions suggests that propionate fermentation and acetate
      utilization were the explanatory factors for community establishment and re
      establishment.

PMID- 30289886
TI  - A reassessment of global antenatal care coverage for improving maternal health
      using sub-Saharan Africa as a case study.
AB  - BACKGROUND: Antenatal period is an opportunity for reaching pregnant women with
      vital interventions. In fact, antenatal care (ANC) coverage was an indicator for
      assessing progress towards the Millennium Development Goals. This paper applies a
      novel index of service coverage using ANC, which accounts for every ANC visit. An
      index of service coverage gap is also proposed. These indices are additively
      decomposable by population groups and they are sensitive to the receipt of more
      ANC visits below a defined threshold. These indices have also been generalised to
      account for the quality of services. METHODS: Data from recent rounds of the
      Demographic and Health Survey (DHS) are used to reassess ANC service coverage in
      35 sub-Saharan African countries. An index of ANC coverage was estimated. These
      countries were ranked, and their ranks are compared with those based on attaining
      at least four ANC visits (ANC4+). FINDINGS: The index of ANC coverage reflected
      the level of service coverage in countries. Further, disparities exist in country
      ranking as some countries, e.g. Cameroon, Benin Republic and Nigeria are ranked
      better using the ANC4+ indicator but poorly using the proposed index. Also,
      Rwanda and Malawi are ranked better using the proposed index. CONCLUSION: The
      proposed ANC index allows for the assessment of progressive realisation, rooted
      in the move towards universal health coverage. In fact, the index reflects
      progress that countries make in increasing service coverage. This is because
      every ANC visit counts. Beyond ANC coverage, the proposed index is applicable to
      assessing service coverage generally including quality education.

PMID- 30289887
TI  - The effect of modified locking methods and suture materials on Zone II flexor
      tendon repair-An ex vivo study.
AB  - The failure rate of intrasynovial tendon repair is high due to substantial
      elongation at the repair site and to the development of adhesions between the
      tendon's surface and the surrounding digital sheath. To minimize these
      complications, we sought to reduce the incidence of gapping and to facilitate the
      initiation of early motion by improving the time zero structural properties of
      repair. The Winters-Gelberman 8-strand repair technique was modified by adding
      surface lock loops and by using Fiberwire suture material. Forty-eight canine
      flexor digitorum profundus tendons were transected and repaired with one of three
      8-strand techniques (Pennington modified Kessler, half hitch loops, or surface
      locking Kessler) using either 3-0 Supramid or 4-0 Fiberwire suture. Biomechanical
      testing was performed to determine the physiologic and failure mode properties of
      the repairs. The surface locking Kessler technique improved repair maximum load,
      load necessary to create a 2 mm repair site gap, and yield force compared to the
      modified Kessler and half hitch loop techniques. Fiberwire suture improved
      maximum load, the load necessary to create a 2 mm repair site gap, stiffness, and
      yield force compared to Supramid suture. Failure occurred by both suture pull out
      and by suture breakage in the modified Kessler, Supramid suture repair group.
      Failure occurred consistently by suture breakage in the surface locking Kessler,
      Supramid suture repair group. These results reveal that a novel locking Kessler
      repair is significantly stronger than the current state-of-the art flexor tendon
      suture repair technique. The use of a surface locking Kessler technique with
      Fiberwire suture markedly improves the mechanical properties of intrasynovial
      tendon repair by reducing the risk of post-operative gapping and rupture.

PMID- 30289889
TI  - Habitat complexity and benthic predator-prey interactions in Chesapeake Bay.
AB  - In Chesapeake Bay, the soft-shell clam Mya arenaria (thin-shelled, deep
      burrowing) exhibits population declines when predators are active, and it
      persists at low densities. In contrast, the hard clam Mercenaria mercenaria
      (thick-shelled, shallow-burrowing) has a stable population and age distribution.
      We examined the potential for habitat and predators to control densities and
      distributions of bivalves in a field caging experiment (Mya only) and laboratory
      mesocosm experiments (both species). In the field, clams exposed to predators
      experienced 76.3% greater mortality as compared to caged individuals, and blue
      crabs were likely responsible for most of the mortality of juvenile Mya. In
      mesocosm experiments, Mya had lower survival in sand and seagrass than in shell
      hash or oyster shell habitats. However, crabs often missed one or more prey items
      in seagrass, shell, and oyster shell habitats. Predator search times and
      encounter rates declined when prey were at low densities, likely due to the added
      cost of inefficient foraging; however, this effect was more pronounced for Mya
      than for Mercenaria. Mercenaria had higher survival than Mya in mesocosm
      experiments, likely because predators feeding on Mercenaria spent less time
      foraging than those feeding on Mya. Mya may retain a low-density refuge from
      predation even with the loss of structurally complex habitats, though a loss of
      habitat refuge may result in clam densities that are not sustainable. A better
      understanding of density-dependent predator-prey interactions is necessary to
      prevent loss of food-web integrity and to conserve marine resources.

PMID- 30289888
TI  - Species identity matters when interpreting trophic markers in aquatic food webs.
AB  - In aquatic systems, food web linkages are often assessed using diet contents,
      stable isotope ratios, and, increasingly, fatty acid composition of organisms.
      Some correlations between different trophic metrics are assumed to be well
      supported; for example, particular stable isotope ratios and fatty acids seem to
      reflect reliance on benthic or pelagic energy pathways. However, understanding
      whether the assumed correlations between different trophic metrics are coherent
      and consistent across species represents a key step toward their effective use in
      food web studies. To assess links among trophic markers, we compared
      relationships between major diet components, fatty acids, and stable isotope
      ratios in three fishes: yellow perch (Perca flavescens), round goby (Neogobius
      melanostomus), and spottail shiner (Notropis hudsonius) collected from nearshore
      Lake Michigan. Yellow perch and spottail shiner are native in this system, while
      round goby are a relatively recent invader. We found some evidence for agreement
      between different trophic metrics, especially between diet components, n-3:n-6
      fatty acid ratios, and stable isotope ratios (delta13C and delta15N). However, we
      also observed significant variation in observed relationships among markers and
      species, potentially due to taxonomic variation in the specific diet items
      consumed (e.g., chydorid microcrustaceans and Dreissena mussels) and species
      specific biochemical processes. In many of these latter cases, the invasive
      species differed from the native species. Understanding the effects of taxonomic
      variation on prey and predator signatures could significantly improve the
      usefulness of fatty acids in food web studies, whereas diet contents and stable
      isotopes appear to be reliable indicators of trophic niche in aquatic food webs.

PMID- 30289890
TI  - Did you choose appropriate tracer for retrograde tracing of retinal ganglion
      cells? The differences between cholera toxin subunit B and Fluorogold.
AB  - Cholera toxin subunit B (CTB) and Fluorogold(FG) are two widely utilized
      retrograde tracers to assess the number and function of retinal ganglion cells
      (RGCs). However, the relative advantages and disadvantages of these tracers
      remain unclear, which may lead to their inappropriate application. In this study,
      we compared these tracers by separately injecting the tracer into the superior
      Colliculi (SC) in rats, one or 2 weeks later, the rats were sacrificed, and their
      retinas, brains, and optic nerves were collected. From the first to second week,
      FG displayed a greater number of labeled RGCs and a larger diffusion area in the
      SC than CTB; The number of CTB labeled RGCs and the diffusion area of CTB in the
      SC increased significantly, but there was no distinction between FG; Furthermore,
      CTB exhibited more labeled RGC neurites and longer neurites than FG, but no
      difference was evident between the same trace; The optic nerves labeled using CTB
      were much clearer than those labeled using FG. In conclusion, both CTB and FG can
      be used for the retrograde labeling of RGCs in rats at 1 or 2 weeks. FG achieves
      retrograde labeling of a greater number of RGCs than CTB, whereas CTB better
      delineates the morphology of RGCs. Furthermore, CTB seems more suitable for
      retrograde labeling of some small, non-image forming nuclei in the brain to which
      certain RGC subtypes project their axons.

PMID- 30289891
TI  - A quantile regression forest based method to predict drug response and assess
      prediction reliability.
AB  - Drug response prediction is a critical step for personalized treatment of cancer
      patients and ultimately leads to precision medicine. A lot of machine-learning
      based methods have been proposed to predict drug response from different types of
      genomic data. However, currently available methods could only give a "point"
      prediction of drug response value but fail to provide the reliability and
      distribution of the prediction, which are of equal interest in clinical practice.
      In this paper, we proposed a method based on quantile regression forest and
      applied it to the CCLE dataset. Through the out-of-bag validation, our method
      achieved much higher prediction accuracy of drug response than other available
      tools. The assessment of prediction reliability by prediction intervals and its
      significance in personalized medicine were illustrated by several examples.
      Functional analysis of selected drug response associated genes showed that the
      proposed method achieves more biologically plausible results.

PMID- 30289892
TI  - The TLR1 gene is associated with higher protection from leprosy in women.
AB  - Leprosy is an infectious disease with a complex genetic and immunological
      background. Polymorphisms in genes that encode cytokines and receptors involved
      in the immune response, such as the Toll-like receptor 1 (TLR1), may be
      associated with disease risk. We hypothesized that polymorphisms in innate
      immunity genes confer susceptibility to leprosy that differs between women and
      men. In this study, we investigate sex differences in the association between a
      single nucleotide polymorphism (SNP) in TLR1 and Nucleotide-binding
      oligomerization domain containing 2 (NOD2) genes and leprosy susceptibility in
      256 clinically classified leprosy patients and 233 control subjects in a
      Brazilian population. Our results showed no association between the SNP rs8057341
      in NOD2 and leprosy in this population. However, the heterozygous genotype of the
      TLR1 SNP (rs4833095) showed a statistically significant association in women (OR
      = 0.54, P = 0.02). Our findings suggest that the TLR1 polymorphism was associated
      with an increased protection from leprosy in women.

PMID- 30289893
TI  - Design and evaluation of selective butyrylcholinesterase inhibitors based on
      Cinchona alkaloid scaffold.
AB  - This paper describes the synthesis and anticholinesterase potency of Cinchona
      based alkaloids; ten quaternary derivatives of cinchonines and their
      corresponding pseudo-enantiomeric cinchonidines. The quaternization of
      quinuclidine moiety of each compound was carried out with groups diverse in their
      size: methyl, benzyl and differently meta- and para-substituted benzyl groups.
      All of the prepared compounds reversibly inhibited human butyrylcholinesterase
      and acetylcholinesterase with Ki constants within nanomolar to micromolar range.
      Five cinchonidine derivatives displayed 95-510 times higher inhibition
      selectivity to butyrylcholinesterase over acetylcholinesterase and four were
      potent butyrylcholinesterase inhibitors with Ki constants up to 100 nM, of which
      N-para-bromobenzyl cinchonidinium bromide can be considered a lead for further
      modifications and optimizations for possible use in the treatment of
      neurodegenerative diseases.

PMID- 30289895
TI  - Investigating the effect of wearing the hijab: Perception of facial
      attractiveness by Emirati Muslim women living in their native Muslim country.
AB  - The Hijab and other forms of Islamic veiling are important social, cultural, and
      religious symbols that are central to the identity of millions of Muslim women
      across the world. However, despite the large body of literature that exists on
      the political and socio-cultural aspects of Islamic veiling, little is known
      about how the appearance of women wearing the hijab is perceived by other Muslim
      women within their native Muslim country. To throw light on this important issue,
      the current study focussed on the effects of the hijab on female facial
      attractiveness perceived by practising Muslim Emirati women living in their
      native Muslim country (the United Arab Emirates) who themselves wore the hijab as
      everyday attire. Participants were shown frontal-head images of women in three
      different conditions: covered (heads fully covered by the hijab except for the
      face), partially covered (heads fully covered by the hijab except for the face
      and the hair around the forehead) and uncovered (heads with no covering). The
      findings showed that faces in images where heads were covered and partially
      covered by the hijab were rated as equally attractive but both were rated as
      significantly less attractive than faces in images where heads were uncovered.
      These findings suggest that, even for practising Muslim Emirati females living in
      their native Muslim country for whom wearing the hijab is a normal aspect of
      everyday life, perception of facial attractiveness is compromised by wearing this
      garment. We argue that this effect of wearing the hijab is not consistent with a
      preference for one's own cultural group (cultural endogamy) and may, instead,
      occur because wearing a hijab occludes external features, such as hair and ears,
      which normally contribute to the perception of human facial attractiveness. In
      sum, while wearing the hijab may be dominated by male attitudes towards
      suppressing female attractiveness towards males, the findings from this study
      suggest that female Muslims too perceive the negative influence of wearing the
      hijab on female facial attractiveness.

PMID- 30289894
TI  - The impact of heat and impaired kidney function on productivity of Guatemalan
      sugarcane workers.
AB  - BACKGROUND: Climate change has implications for human health and productivity.
      Models suggest that heat extremes affect worker health, reduce labor capacity,
      and commodity supply. Chronic health conditions are on the rise internationally.
      However there is a paucity of direct empirical evidence relating increasing
      temperatures to both agricultural worker health and productivity. METHODS AND
      FINDINGS: We evaluated the relationship between temperature exposure, kidney
      function, and two measures of productivity-tons of commodity produced and job
      attrition, of 4,095 Guatemalan sugarcane cutters over a 6-month harvest. We used
      distributed lag non-linear models to evaluate associations between wet bulb globe
      temperature (WBGT) and productivity of workers with normal or impaired kidney
      function. The cumulative effect of exposure to a max WBGT of 34 degrees C was
      1.16 tons (95% CI: -2.87, 0.54) less sugarcane cut over the next five days by
      workers with impaired kidney function, compared to exposure to 29 degrees C.
      Impaired kidney function was associated with premature workforce attrition.
      Workers starting the harvest season with impaired kidney function were more than
      twice as likely to leave employment (HR: 2.92, 95% CI: 1.88, 4.32). CONCLUSIONS:
      Heat extremes may be associated with loss of agricultural worker productivity and
      employment, especially among those with impaired kidney function. Agricultural
      workers who develop health conditions, such as kidney disease, are particularly
      vulnerable in the face of climate change and increasing heat extremes. The
      resultant loss of employment and productivity has significant implications for
      global commodity supplies.

PMID- 30289897
TI  - Security and efficiency enhancement of an anonymous three-party password
      authenticated key agreement using extended chaotic maps.
AB  - Recently, Lu et al. claimed that Xie et al.'s three-party password-authenticated
      key agreement protocol (3PAKA) using chaotic maps has three security
      vulnerabilities; in particular, it cannot resist offline password guessing
      attack, Bergamo et al.'s attack and impersonation attack, and then they proposed
      an improved protocol. However, we demonstrate that Lu et al.'s attacks on Xie et
      al.'s scheme are unworkable, and their improved protocol is insecure against
      stolen-verifier attack and off-line password guessing attack. Furthermore, we
      propose a novel scheme with enhanced security and efficiency. We use formal
      verification tool ProVerif, which is based on pi calculus, to prove security and
      authentication of our scheme. The efficiency of the proposed scheme is higher
      than other related schemes.

PMID- 30289896
TI  - Proportion of adults in the general population of Stockholm County who want
      gender-affirming medical treatment.
AB  - The number of patients presenting for care at gender clinics is increasing, yet
      the proportion of adults in the general population who want gender-affirming
      medical treatment remains essentially unknown. We measured the wish for cross-sex
      hormones or gender-affirming surgery, as well as other aspects of gender
      incongruence, among the general adult population of Stockholm County, Sweden. A
      population-representative sample of 50,157 Stockholm County residents ages 22 and
      older comprise the Stockholm Public Health Cohort. They were enrolled in 2002,
      2006, and 2010 and followed-up in roughly 4-year intervals, with questions on
      health, lifestyle and social characteristics. In 2014, participants received the
      item "I would like hormones or surgery to be more like someone of a different
      sex." Two additional items concerned other aspects of gender incongruence: "I
      feel like someone of a different sex", and "I would like to live as or be treated
      as someone of a different sex." Each item had four answer options ("Not at all
      correct", "Somewhat or occasionally correct", "Quite correct", and "Absolutely
      correct"). For each item, any of the three affirmative answer choices were
      considered as some level of agreement. Calibration weights were used to estimate
      population-representative rates with 95% confidence intervals. The desire for
      cross-sex hormones or surgery was reported by 0.5% (95% CI, 0.4%-0.7%) of
      participants. Feeling like someone of a different sex was reported by 2.3% (95%
      CI, 2.1%-2.6%). Wanting to live as or be treated as a person of another sex was
      reported by 2.8% (95% CI, 2.4%-3.1%). These findings greatly exceed estimates of
      the number of patients receiving gender-affirming medical care. Clinicians must
      be prepared to recognize and care for patients experiencing discomfort due to
      gender incongruence and those who would like gender-affirming medical treatment.

PMID- 30289899
TI  - Forensic analysis of Turkish elections in 2017-2018.
AB  - With a majority of 'Yes' votes in the Constitutional Referendum of 2017, Turkey
      continued its drift towards an autocracy. By the will of the Turkish people, this
      referendum transferred practically all executive power to president Erdogan.
      However, the referendum was confronted with a substantial number of allegations
      of electoral misconducts and irregularities, ranging from state coercion of 'No'
      supporters to the controversial validity of unstamped ballots. Here we report the
      results of an election forensic analysis of recent Turkish elections to clarify
      to what extent it is plausible that these voting irregularities were present and
      able to influence the outcome of the referendum. We apply statistical forensics
      tests to identify the specific nature of the alleged electoral malpractices. In
      particular, we test whether the data contains fingerprints for ballot stuffing
      (submission of multiple ballots per person during the vote) and voter rigging
      (coercion and intimidation of voters). Additionally, we perform tests to identify
      numerical anomalies in the election results. For the 2017 Constitutional
      Referendum we find systematic and highly significant statistical support for the
      presence of both ballot stuffing and voter rigging. In 11% of stations we find
      signs for ballot stuffing with a standard deviation (uncertainty of ballot
      stuffing probability) of 2.7% (4 sigma event). Removing such ballot-stuffing
      characteristic anomalies from the data would tip the overall balance from 'No' to
      a majority of 'Yes' votes. The 2017 election was followed by early elections in
      2018 to directly vote for a new president who would now be head of state and
      government. We find statistical irregularities in the 2018 presidential and
      parliamentary elections similar in size and direction to those in 2017. These
      findings validate that our results unveil systematic and potentially even
      fraudulent biases that require further attention in order to combat electoral
      malpractices.

PMID- 30289898
TI  - Expected changes in obesity after reformulation to reduce added sugars in
      beverages: A modeling study.
AB  - BACKGROUND: Several strategies have been proposed to reduce the intake of added
      sugars in the population. In Mexico, a 10% sugar-sweetened beverages (SSBs) tax
      was implemented in 2014, and the implementation of other nutritional policies,
      such as product reformulation to reduce added sugars, is under discussion. WHO
      recommends that all individuals consume less than 10% of their total energy
      intake (TEI) from added sugars. We propose gradually reducing added sugars in
      SSBs to achieve an average 10% consumption of added sugars in the Mexican
      population over 10 years and to estimate the expected impact of reformulation in
      adult body weight and obesity. METHODS AND FINDINGS: Baseline consumption for
      added sugars and SSBs, sex, age, socioeconomic status (SES), height, and weight
      for Mexican adults were obtained from the 2012 Mexico National Health and
      Nutrition Survey (ENSANUT). On average, 12.6% of the TEI was contributed by added
      sugars; we defined a 50% reduction in added sugars in SSBs over 10 years as a
      reformulation target. Using a dynamic weight change model, sugar reductions were
      translated into individual expected changes in body weight assuming a 43% caloric
      compensation and a 2-year lag for the full effect of reformulation to occur.
      Results were stratified by sex, age, and SES. Twelve years after reformulation,
      the TEI from added sugars is expected to decrease to 10%, assuming no
      compensation from added sugars; 44% of the population would still be above WHO
      recommendations, requiring further sugar reductions to food. Body weight could be
      reduced by 1.3 kg (95% CI -1.4 to -1.2) in the adult population, and obesity
      could decrease 3.9 percentage points (pp; -12.5% relative to baseline). Our
      sensitivity analyses suggest that the impact of the intervention could vary from
      0.12 kg after 6 months to 1.52 kg in the long term. CONCLUSIONS: Reformulation to
      reduce added sugars in SSBs could produce large reductions in sugar consumption
      and obesity in the Mexican adult population. This study is limited by the use of
      a single dietary recall and by data collected in all seasons except summer;
      still, these limitations should lead to conservative estimates of the
      reformulation effect. Reformulation success could depend on government
      enforcement and industry and consumer response, for which further research and
      evidence are needed.

PMID- 30289900
TI  - Knowledge gaps among South African healthcare providers regarding the prevention
      of neonatal group B streptococcal disease.
AB  - OBJECTIVE: To evaluate obstetric healthcare provider knowledge regarding the
      prevention of group B streptococcal disease in South African infants. METHODS:
      Questionnaires exploring knowledge, attitudes and beliefs around group B
      streptococcal prevention were administered to consenting doctors and maternity
      nurses in a tertiary academic hospital. Qualitative assessments (focus groups)
      were undertaken with junior doctors and nurses. RESULTS: 238 participants
      completed the questionnaire: 150 (63.0%) doctors and 88 (37.0%) nurses. Overall,
      22.7% of participants correctly identified the risk-based prevention protocol
      recommended at this hospital. Most doctors (68.0%) and nurses (94.3%) could not
      correctly list a single risk factor. A third of doctors did not know the correct
      antibiotic protocols, and most (80.0%) did not know the recommended timing of
      antibiotics in relation to delivery. Focus group discussions highlighted the lack
      of knowledge, awareness and effective implementation of protocols regarding
      disease prevention. CONCLUSIONS: Our study highlighted knowledge gaps on the risk
      based prevention strategy in a setting which has consistently reported among the
      highest incidence of invasive group B streptococcal disease globally. In these
      settings, education and prioritization of the risk-based intrapartum antibiotic
      strategy is warranted, but an alternative vaccine-based strategy may prove more
      effective in preventing invasive group B streptococcal disease in the long-term.

PMID- 30289901
TI  - Human-modified biogeographic patterns and conservation in game birds: The dilemma
      of the black francolin (Francolinus francolinus, Phasianidae) in Pakistan.
AB  - The ever-increasing human-mediated wildlife reshuffling is raising concern for
      the conservation of biodiversity. The loss of biological distinctiveness among
      regions lessens the genetic diversity and consequently the evolutionary potential
      of local biotas to tackle present-day global change and human disturbance. This
      process may be sometimes cryptic unless investigated by means of a molecular
      approach. In this respect, game birds are a paradigmatic case. The black
      francolin (Francolinus francolinus, Phasianidae) is a medium-sized galliform
      whose distribution range stretches from Cyprus to the Gulf of Bengal. Six
      morphologic subspecies are known, with three of which occurring in Pakistan,
      where the species is heavily hunted and used as pet for chirping competitions. We
      genotyped 98 samples (feathers) at both the entire mitochondrial DNA Control
      Region gene and nine microsatellite loci to get a deeper insight into the genetic
      diversity of the black francolin in Pakistan in order to offer cogent
      recommendations for its conservation management. We identified several mtDNA
      lineages that were consistent with the currently described subspecies/taxonomy
      whose pattern of co-occurrence is compatible with the geological history and the
      faunal movement routes of the region under study. However, the biparentally
      inherited microsatellites returned a quite discordant picture of an extensive,
      sex-biased genetic mixing due to the intensive relocations of already
      overharvested male individuals for chirping competitions. Our results indicated
      that the genetic integrity of the black francolin in Pakistan could be seriously
      at risk and call for monitoring and limiting its trade other than enhancing the
      public awareness of the importance of local biodiversity resources.

PMID- 30289903
TI  - Willingness-to-pay for sustainable beer.
AB  - Breweries across the country are investing in energy efficient and low-carbon
      brewing practices. Drawing insights from the sustainable consumption and
      ecological economics literature, this analysis evaluates whether consumers are
      willing to pay more for sustainable beer and what predicts the value of the
      premium. Based on a survey of beer consumers from across the U.S. that contained
      one of two willingness-to-pay exercises, we evaluate what respondent attributes
      are associated with a higher willingness-to-pay for sustainably brewed beer. We
      find that the majority of beer consumers are willing to pay more for sustainable
      beer. Consumers who are prepared to pay a premium tend to already pay more per
      unit of beer, are more aware of their purchasing behavior and the manner in which
      their consumption patterns may affect the environment, and pursue lifestyles
      based on professional advancement, helping the environment, and helping other
      causes.

PMID- 30289902
TI  - Identification of the novel deletion-type PML-RARA mutation associated with the
      retinoic acid resistance in acute promyelocytic leukemia.
AB  - All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are essential for acute
      promyelocytic leukemia (APL) treatment. It has been reported that mutations in
      PML-RARA confer resistance to ATRA and ATO, and are associated with poor
      prognosis. Although most PML-RARA mutations were point mutations, we identified a
      novel seven amino acid deletion mutation (p.K227_T233del) in the RARA region of
      PML-RARA in a refractory APL patient. Here, we analyzed the evolution of the
      mutated clone and demonstrated the resistance of the mutated clone to retinoic
      acid (RA). Mutation analysis of PML-RARA was performed using samples from a
      chemotherapy- and ATRA-resistant APL patient, and the frequencies of mutated PML
      RARA transcript were analyzed by targeted deep sequencing. To clarify the
      biological significance of the identified PML-RARA mutations, we analyzed the
      ATRA-induced differentiation and PML nuclear body formation in mutant PML-RARA
      transduced HL-60 cells. At molecular relapse, the p.K227_T233del deletion and the
      p.R217S point-mutation in the RARA region of PML-RARA were identified, and their
      frequencies increased after re-induction therapy with another type of retinoiec
      acid (RA), tamibarotene. In deletion PML-RARA-transduced cells, the CD11b
      expression levels and NBT reducing ability were significantly decreased compared
      with control cells and the formation of PML nuclear bodies was rarely observed
      after RA treatment. These results indicate that this deletion mutation was
      closely associated with the disease progression during RA treatment.

PMID- 30289904
TI  - Survey on opinions and usage patterns for the ResearchGate platform.
AB  - Based on a survey, the following study investigates opinions and also usage
      patterns relating to the ResearchGate social networking site for scientists and
      researchers. The survey consisted of 19 questions and was conducted online with
      695 scientists from the disciplines of physics, biology, medicine, and
      neuroscience. Amongst other issues, the research questions concerned how much
      time and effort the interviewees expended on ResearchGate, what added value they
      perceived in using the site, the extent to which social aspects influence use,
      how participants planned to use the platform in future, and what role
      ResearchGate's own metric, the RG score, played for the scientists. In addition,
      we discuss which of the factors of age, sex, origin, and scientific discipline
      have a decisive influence on the responses of the interviewees and which are of
      no statistical significance The results clearly show that the origin of the
      participants is frequently decisive, but that the remaining factors also have a
      considerable influence on the responses for more than 25% of the questions.

PMID- 30289906
TI  - Correction: Understanding plastome evolution in Hemiparasitic Santalales:
      Complete chloroplast genomes of three species, Dendrotrophe varians, Helixanthera
      parasitica, and Macrosolen cochinchinensis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0200293.].

PMID- 30289905
TI  - ComOn-Coaching: The effect of a varied number of coaching sessions on transfer
      into clinical practice following communication skills training in oncology:
      Results of a randomized controlled trial.
AB  - OBJECTIVE: To investigate the effect of the number of coaching sessions after
      communication skills training on the medical communicative performance of
      oncologists in clinical practice. METHODS/DESIGN: The training, consisting of a
      workshop and one (control group) vs. four (intervention group) sessions of
      individual coaching, was evaluated in a randomized controlled trial. Eligible
      participants included physicians working in any setting where patients with
      oncological diseases were treated. Real medical consultations were video recorded
      at three time points: before the workshop (t0), after the workshop (t1) and after
      completion of coaching (t2). The 1.5-day workshop was based on role-playing in
      small groups; in the coaching sessions, the videos recorded at t1 were analyzed
      in detail by both the trainer and the physician. The coaching sessions were
      manualized and based on the physician's learning goals. The primary hypothesis
      was that the intervention group would improve to a higher extent than the control
      group, as assessed by external raters using rating scales specially developed for
      this project. Physicians were stratified for sex and setting and randomized by an
      independent statistician. The group assignment was revealed for physicians and
      trainers at the end of the workshop, while the raters were blinded to group
      assignments and assessment points. RESULTS: A total of 72 physicians participated
      in one of 8 workshops and could be allocated to either the control or
      intervention group. The intervention group showed a statistically significant
      improvement (ES d = 0.41, p<.01) in the All items domain of the rating scales
      between t1 and t2 and showed a significant advantage compared with the CG (ES =
      .41, p = .04). The impact on diverse specified skills was heterogeneous; a larger
      sample is necessary for more detailed analysis. CONCLUSIONS: The training
      achieved some observable and significant changes in the communicative behavior of
      oncologists in clinical practice. The four coaching sessions showed some
      significant advantages compared to the single coaching session. Considerable
      effort is necessary to achieve sustained changes in communication in clinical
      every-day practice. Thus, our coaching concept is a promising method for this
      purpose.

PMID- 30289907
TI  - Effect of weighted sled towing on sprinting effectiveness, power and force
      velocity relationship.
AB  - This study aimed to compare the components of force-velocity (F-V) and power
      velocity (P-V) profiles and the mechanical effectiveness of force application (or
      force ratio-RF) among various sled-towing loads during the entire acceleration
      phase of a weighted sled sprint. Eighteen sprinters performed four 50-m sprints
      in various conditions: unloaded; with a load corresponding to 20% of the
      athlete's body mass (BM); with a load of 30% BM; and with a load of 40% BM. Data
      were collected with five video cameras, and the images were digitised to obtain
      velocity from the derivation of the centre-of-mass position. F-V and P-V
      components and RF were estimated from sprinting velocity-time data for each load
      using a validated method that is based on an inverse dynamic approach applied to
      the sprinter's centre-of-mass (it models the horizontal antero-posterior and
      vertical ground reaction force components) and requires only measurement of
      anthropometric and spatiotemporal variables (body mass, stature and instantaneous
      position or velocity during the acceleration phase). The theoretical maximal
      velocity decreased with load compared with the unloaded condition (for 20% BM: 
      6%, effect size (ES) = 0,38; for 30% BM: -15%, ES = 1.02; for 40% BM: -18%, ES =
      1.10). The theoretical maximal horizontal force (F0) and maximal power were not
      different among conditions. However, power at the end of the acceleration phase
      increased with load (40% BM vs 0%: 72%; ES = 2.73) as well as the maximal
      mechanical effectiveness (12%; ES = 0.85). The linear decrease in RF was
      different between 30 or 40% BM and the unloaded condition (-23%; ES = 0.74 and
      0.66). Better effectiveness may be developed with 40% BM load at the beginning of
      the acceleration and with the various load-induced changes in the components of
      the F-V and P-V relationships, allowing a more accurate determination of optimal
      loading conditions for maximizing power.

PMID- 30289908
TI  - Understanding drivers of human-leopard conflicts in the Indian Himalayan region:
      Spatio-temporal patterns of conflicts and perception of local communities towards
      conserving large carnivores.
AB  - Human killing is the decisive and most critical expression of human-leopard
      conflict and needs to be addressed sensitively to maintain local support for
      leopard conservation in India. This research was undertaken to investigate the
      ecological aspects of human killing and injury, spatial characteristic and
      pattern of such sites, temporal and seasonal trends of attacks and perception of
      local communities towards leopard in the Indian Himalayan region (IHR). We
      surveyed two sites i) Pauri Garhwal in the western part and ii) North Bengal
      (Dooars) in the eastern part of IHR, compiled secondary data on human-leopard
      conflict records and made field visits to (N = 101) conflict sites. We also
      conducted (N = 186) semi-structured questionnaire surveys in each of the sites to
      assess perception of local communities towards leopard. We analyzed the conflict
      data using rare events model in a binary logistic regression framework to
      understand spatial patterns of such incidents for Pauri Garhwal and North Bengal.
      The average number of injuries and deaths to leopard attacks in Pauri was
      estimated to be 11 (SE 1.13) and 3 (SE 0.6) per year between 2006-2016 whereas in
      North Bengal it was estimated to be 70 (SE 9.2) and 1.6 (SE 0.3) respectively
      between 2004-2016. About 97% of the leopard attacks in North Bengal and 60% of
      the leopard attacks in Pauri resulted in human injuries. Majority of the leopard
      attack victims in Pauri were children and young people, whereas in North Bengal
      it was middle aged tea estate workers. Attack on humans in Pauri were recorded
      mostly near areas with dense scrub cover whereas in North Bengal it was reported
      within tea-estates. The percentage of human deaths to leopard attacks in Pauri
      were higher (40%) compared to a mere (3%) in North Bengal. Forty-one percent of
      respondents in Pauri and 75% in North Bengal were positive towards presence and
      conservation of leopard. A predictive risk map revealed central and northern
      regions of Pauri Garhwal and protected areas, peripheral areas in central and
      south-western dooars (North Bengal) as high "human-leopard conflict risk zones".
      This analytical procedure can be adopted in other sites to identify potential
      human-carnivore conflict risk zones.

PMID- 30289909
TI  - Predictors of enophthalmos among adult patients with pure orbital blowout
      fractures.
AB  - The aim of this study was to determine the predictors of post-traumatic
      enophthalmos (PE) in relation to the internal orbital changes following pure
      orbital blowout fractures. The design was a 10-year retrospective cross-sectional
      study analysing 629 medical records and computed tomography (CT) data of patients
      with orbital fractures from January 2008 to January 2017. Demographic, etiology,
      co-morbidity and clinical characteristics were obtained from the medical records.
      Assessment of the PE, fracture site and size, intraorbital structures and muscle
      change were performed using the Digital Imaging and Communications in Medicine
      (DICOM) viewer software, OsiriX v5.8.2. Of the 629 patients with orbital
      fractures, 87 were pure orbital blowout fractures. Demographic pattern showed
      that males outnumbered females in the series, with male: female ratio of 5.7:1.
      The mean age was 37.2 +/- 14.7 and the main etiology was motor vehicle accident.
      Orbital floor fracture was the most common fracture location (67.8%). The
      involvement of the posterior ledge and inferior orbital fissure showed
      statistical significant difference with PE (Fisher's exact test, p = 0.03).
      Binary logistic regression showed that after controlling for age, patients with
      fracture size of more than 150 mm2 had three times the odds of sustaining a PE,
      (adjusted odds ratio (AOR) = 3.01 (95% CI 1.17-7.92). Fracture size larger than
      150 mm2 was a radiological predictor of PE. Additional research investigating
      further on the role of concurrent fracture of the posterior ledge and inferior
      orbital fissure is advocated.

PMID- 30289910
TI  - Overexpression of the Sorghum bicolor SbCCoAOMT alters cell wall associated
      hydroxycinnamoyl groups.
AB  - Sorghum (Sorghum bicolor) is a drought tolerant crop, which is being developed as
      a bioenergy feedstock. The monolignol biosynthesis pathway is a major focus for
      altering the abundance and composition of lignin. Caffeoyl coenzyme-A O
      methyltransferase (CCoAOMT) is an S-adenosyl methionine (SAM)-dependent O
      methyltransferase that methylates caffeoyl-CoA to generate feruloyl-CoA, an
      intermediate required for the biosynthesis of both G- and S-lignin. SbCCoAOMT was
      overexpressed to assess the impact of increasing the amount of this enzyme on
      biomass composition. SbCCoAOMT overexpression increased both soluble and cell
      wall-bound (esterified) ferulic and sinapic acids, however lignin concentration
      and its composition (S/G ratio) remained unaffected. This increased deposition of
      hydroxycinnamic acids in these lines led to an increase in total energy content
      of the stover. In stalk and leaf midribs, the increased histochemical staining
      and autofluorescence in the cell walls of the SbCCoAOMT overexpression lines also
      indicate increased phenolic deposition within cell walls, which is consistent
      with the chemical analyses of soluble and wall-bound hydroxycinnamic acids. The
      growth and development of overexpression lines were similar to wild-type plants.
      Likewise, RNA-seq and metabolite profiling showed that global gene expression and
      metabolite levels in overexpression lines were also relatively similar to wild
      type plants. Our results demonstrate that SbCCoAOMT overexpression significantly
      altered cell wall composition through increases in cell wall associated
      hydroxycinnamic acids without altering lignin concentration or affecting plant
      growth and development.

PMID- 30289913
TI  - Isolation and exploitation of minority: Game theoretical analysis.
AB  - We investigate various group-size distributions occurring in a situation where
      each group's resource is exposed to appropriation by other groups. The amount of
      appropriation depends on the size difference between groups. Our work focuses on
      the cases where the entire community isolates a small group or even an individual
      to maximize its gain. While people's basic motivation to form a group can be
      understood based on the group-size effect on multiplying a collective asset,
      sensitive factors that induce a asymmetric group distribution are the group
      efficiency and the ratio of secured assets to assets pending in a competition. We
      show that social rejection to a minor group may occur when the group efficiency
      is relatively low and their asset is severely exposed to possible appropriation.

PMID- 30289911
TI  - Dietary polysaccharide-rich extract from Eucheuma cottonii modulates the
      inflammatory response and suppresses colonic injury on dextran sulfate sodium
      induced colitis in mice.
AB  - Inflammatory bowel disease (IBD) is a known medical burden in most developed
      countries and a significant cause of morbidity. The IBD label includes Crohn's
      disease (CD) and ulcerative colitis (UC). Pharmacological and surgical
      intervention are the two main management approaches for IBD. Some drugs have been
      developed for IBD therapy, but accessibility is limited due to high costs.
      Furthermore, these agents have demonstrated inactivity over long-term treatment
      courses. Therefore, an urgent need is present for new treatment options that are
      safe, able to sustain clinical remission, and improve mucosal gut healing.
      Seaweed has received much attention in the pharmacological field owing to its
      various biomedical properties, including the prolongation of blood clotting time,
      as well as antitumor, anti-inflammation, and antioxidant effects. This study
      therefore aimed to examine the effects of a dietary polysaccharide-rich extract
      obtained from Eucheuma cottonii (EC) on a model of colitis. Colitis was induced
      in male BALB/c mice by the administration of 2.5% (w/v) dextran sulfate sodium
      (DSS) for 7 days. DSS-induced mice were treated with either one of three
      different doses of EC extracts (0.35, 0.70, and 1.75 g/kg body weight) or
      curcumin as a positive control (0.10 g/kg). Mice were sacrificed post-treatment
      and blood samples were collected. The disease activity index (DAI) and
      inflammatory cytokine levels (tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1beta, IL-6, IL-10) were measured. After treatment for 7 days, EC extract
      administration protected against weight loss and decreased the colon weight per
      length ratio. EC extract administration also decreased pro-inflammatory cytokine
      expression, increased IL-10 levels, and reduced colonic damage. Therefore, a
      dietary polysaccharide-rich extract from E. cottonii reduced DSS-induced bowel
      inflammation, thereby becoming a promising candidate for the treatment of
      colitis.

PMID- 30289912
TI  - Targeting obstetric providers in interventions for obesity and gestational weight
      gain: A systematic review.
AB  - BACKGROUND: Providers need to be comfortable addressing obesity and gestational
      weight gain so they may give appropriate care; however, health care providers
      lack guidelines for the most effective educational strategies to assist in
      providing optimal care. OBJECTIVE: To identify studies that involved the
      obstetric provider in interventions for either the perinatal management of
      obesity and/or gestational weight gain in a systematic review. SEARCH STRATEGY: A
      keyword search of databases was performed up to April 2017. SELECTION CRITERIA:
      Obstetric providers who participated in an intervention with the aim to change a
      provider's clinical practice, knowledge, and/or satisfaction with the
      intervention in relation to the perinatal management of obesity or gestational
      weight gain were included. Provider intervention could include training or
      education, changes in systems or organization of care, or resources to support
      practice. PROSPERO database #42016038921. DATA COLLECTION AND ANALYSIS: Bias was
      assessed according to the validated Mixed Methods Appraisal Tool. The following
      variables were synthesized: study location and setting, provider and patient
      characteristics, intervention features, outcomes and efficacy, and strengths and
      weakness. MAIN RESULTS: Of the 6,821 abstracts screened, seven studies (4
      quantitative, 3 mixed-methods) with a total of 335 providers met the inclusion
      criteria; two of which focused on the management of obesity, three focused on
      gestational weight gain, and two focused on both topics. Interventions that
      incorporated motivational interviewing skills (n = 2), required additional
      training for the research study and addressed specific knowledge deficits such as
      nutrition and exercise (n = 3), and interfaced with the electronic medical record
      (n = 1) demonstrated the greatest impact on provider outcomes. Provider reported
      satisfaction scores were generally favorable, but none addressed provider-level
      efficacy in practice change. CONCLUSIONS: Given the limited number of studies,
      varying range of provider participation, and lack of provider-level efficacy,
      further evaluation of provider training and involvement in interventions for
      perinatal obesity or gestational weight gain is indicated to determine best
      practices for provider and patient outcomes.

PMID- 30289914
TI  - Routine analysis of ascitic fluid for evidence of infection in children with
      chronic liver disease: Is it mandatory?
AB  - Ascitic fluid infection is a major cause of morbidity and mortality in cirrhotic
      patients, requiring early diagnosis and therapy. We aimed to determine predictors
      of ascitic fluid infection in children with chronic liver disease. The study
      included 45 children with chronic liver disease and ascites who underwent 66
      paracentesis procedures. Full history taking and clinical examination of all
      patients were obtained including fever, abdominal pain and tenderness and
      respiratory distress. Investigations included: complete blood count, C-reactive
      protein, full liver function tests, ascitic fluid biochemical analysis, cell
      count and culture. Our results showed that patients' ages ranged between 3 months
      to 12 years. Prevalence of ascitic fluid infection was 33.3%. Gram-positive
      bacteria were identified in six cases, and Gram-negative bacteria in five. Fever
      and abdominal pain were significantly more associated with infected ascites (p
      value = 0.004, 0.006). Patients with ascitic fluid infection had statistically
      significant elevated absolute neutrophilic count and C-reactive protein. Logistic
      regression analysis showed that fever, abdominal pain, elevated absolute
      neutrophilic count and positive C-reactive protein are independent predictors of
      ascitic fluid infection. Fever, elevated absolute neutrophilic count and positive
      C-reactive protein raise the probability of ascitic fluid infection by 3.88, 9.15
      and 4.48 times respectively. The cut-off value for C-reactive protein for ascitic
      fluid infection was 7.2 with sensitivity 73% and specificity of 71%. In
      conclusion, prevalence of ascitic fluid infection in pediatric patients with
      chronic liver disease and ascites was 33.3%. Fever, abdominal pain, positive C
      reactive protein and elevated absolute neutrophilic count are strong predictors
      of ascitic fluid infection. Therefore an empirical course of first-line
      antibiotics should be immediately started with presence of any of these
      predictors after performing ascitic fluid tapping for culture and sensitivity. In
      absence of these infection parameters, routine ascitic fluid analysis could be
      spared.

PMID- 30289915
TI  - Lebbiea (Podostemaceae-Podostemoideae), a new, nearly extinct genus with foliose
      tepals, in Sierra Leone.
AB  - Lebbiea grandiflora (Podostemaceae), a rheophytic herb from the Sewa River rapids
      in Sierra Leone, is described as a new species. It is the first new African genus
      of Podostemaceae published for 30 years. First collected in May 2017, the species
      is assessed as Critically Endangered using the IUCN 2012 standard. It is on the
      edge of extinction with a small population at a single site threatened by
      deposition of gravel and sand from alluvial gold and diamond mining upstream, and
      a planned hydro-electric dam. The new genus is unique in Podostemaceae in a) its
      highly developed and robust style-stigma structure in which the bases of the two
      style-stigmas unite to form a bifurcate funneliform-cylindrical structure, with a
      reflexed, blade-like apex that extends half-way around the perimeter of the ovary
      fruit towards the base of the ovary-fruit, b) a specialised andropodium, with
      robust, self-supporting capacity, having differentiated thickened central, and
      angled, thinner marginal areas (in other Podostemaceae the andropodial structures
      are undifferentiated), c) the pillar-like haptera which completely elevate the
      crustose root above the substrate. Lebbiea is placed in Podostemoideae,
      necessitating amplification of the delimitation of that subfamily in which it is
      additionally unique in having the foliose tepals characteristic of the basal
      subfamilies Weddellinoideae and Tristichoideae.

PMID- 30289916
TI  - Analyzing bovine OCT4 and NANOG enhancer activity in pluripotent stem cells using
      fluorescent protein reporters.
AB  - Green fluorescent protein (GFP) reporters controlled by the regulatory region of
      OCT4 and NANOG-two master regulators for pluripotency are widely used in studies
      of pluripotent stem cell establishment and embryo development. Alongside the
      challenge in establishing bovine pluripotent stem cells, the application of
      bovine-specific gene reporters has rarely been explored. Using lentivirus-based
      GFP reporter, we investigated the upstream regulatory regions of bovine OCT4 and
      NANOG. These reporters show activity in both naive- and primed-state pluripotency
      when infected into mouse and human embryonic stem cells (ESCs), respectively.
      Consistent with what is found in humans and mice, the bovine OCT4-distal enhancer
      (bOCT4-DE) but not the proximal enhancer (bOCT4-PE) region is preferentially
      activated in naive-state pluripotency. Furthermore, the bOCT4-DE region is
      silenced upon conversion of naive-state ESCs into primed-state epiblast stem
      cells (EpiSCs). Co-infection of mouse fibroblasts with the reprograming factors
      for induced pluripotent stem cell (iPSC) induction leads to the generation of GFP
      positive colonies, demonstrating that these GFP reporters can serve as live
      indicators for induced pluripotent cell establishment. We further proved that the
      bovine OCT4 distal enhancer is active in bovine blastocysts. We established the
      lentiviral-based fluorescent reporters controlled by bovine OCT4 and NANOG
      enhancer sequences. These reporter constructs show activity in naive- and primed
      pluripotent states. These reporters may serve as versatile tools for bovine
      ESC/iPSC generation and identification, as well as for developmental studies of
      bovine embryos.

PMID- 30289917
TI  - The common rejection module in chronic rejection post lung transplantation.
AB  - RATIONALE: Recent studies suggest that similar injury mechanisms are in place
      across different solid organ transplants, resulting in the identification of a
      common rejection module (CRM), consisting of 11 genes that are overexpressed
      during acute and, to a lesser extent, chronic allograft rejection. OBJECTIVES: We
      wanted to evaluate the usefulness of the CRM module in identifying acute
      rejection (AR) and different phenotypes of chronic lung transplant rejection
      (CLAD), i.e., bronchiolitis obliterans syndrome (BOS) and restrictive allograft
      syndrome (RAS), using transbronchial brushings, broncho-alveolar lavage (BAL)
      samples, and explant tissue. METHODS: Gene expression measurements for the 11 CRM
      genes (CD6, TAP1, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, and
      BASP1) were performed via qRT-PCR in 14 transbronchial brushings (AR, n = 4; no
      AR, n = 10), 32 BAL samples (stable, n = 13; AR, n = 8; BOS, n = 9; RAS, n = 10),
      and 44 tissue specimens (unused donor lungs, n = 15; BOS, n = 13; RAS, n = 16). A
      geometric mean score was calculated to quantitate overall burden of immune injury
      and a new computational model was built for the most significant genes in lung
      transplant injury. RESULTS: Acute rejection showed a significant difference in
      almost every gene analysed, validating previous observations from microarray
      analysis. RAS tissue demonstrated a higher geometric mean score (6.35) compared
      to donor tissue (4.09, p = 0.018). Analysis of individual CRM genes showed an
      increased expression of ISG20, CXCL10 and CXCL9 in RAS. In BAL samples, no
      differences were detected in gene expression or geometric mean scores between the
      various groups (stable, 5.15; AR, 5.81; BOS, 5.62; RAS, 7.31). A newly modelled 2
      gene tissue CRM score did not demonstrate any difference between BOS and RAS
      (p>0.05). However, the model was able to discriminate RAS from BOS tissue (AUC =
      0.75, 95% CI = 0.55-0.94, p = 0.025). CONCLUSION: Transcriptional tissue analysis
      for CRM genes in CLAD can identify acute rejection and distinguish RAS from BOS.
      The immune activation in RAS seems similar to acute rejection after
      kidney/liver/heart transplantation.

PMID- 30289918
TI  - Simulation of the song motor pathway in birds: A single neuron initiates a chain
      of events that produces birdsong with realistic spectra properties.
AB  - Birdsong is a complex learned behavior regulated by Neuromuscular coordination of
      different muscle sets necessary for producing relevant sounds. We developed a
      heterogeneous and stochastically connected neural network representing the
      pathway from the high vocal center (HVC) to the robust nucleus of the arcopallium
      (RA) neurons that drive the muscles to generate sounds. We show that a single
      active neuron is sufficient to initiate a chain of spiking events that results to
      excite the entire network system. The network could synthesize realistic bird
      sounds spectra, with spontaneous generation of intermittent sound bursts typical
      of birdsong (song syllables). This study confirms experiments on animals and on
      humans, where results have shown that single neurons are responsible for the
      activation of complex behavior or are associated with high-level perception
      events.

PMID- 30289919
TI  - Long-term trends in incidence and risk factors for ischaemic stroke subtypes:
      Prospective population study of the South London Stroke Register.
AB  - BACKGROUND: As the average life expectancy increases, more people are predicted
      to have strokes. Recent studies have shown an increasing incidence in certain
      types of cerebral infarction. We aimed to estimate time trends in incidence,
      prior risk factors, and use of preventive treatments for ischaemic stroke (IS)
      aetiological subtypes and to ascertain any demographic disparities. METHODS AND
      FINDINGS: Population-based data from the South London Stroke Register (SLSR)
      between 2000 and 2015 were studied. IS was classified, based on the underlying
      mechanism, into large-artery atherosclerosis (LAA), cardio-embolism (CE), small
      vessel occlusion (SVO), other determined aetiologies (OTH), and undetermined
      aetiologies (UND). After calculation of age-, sex-, and ethnicity-specific
      incidence rates by subtype for the 16-year period, we analysed trends using
      Cochran-Armitage tests, Poisson regression models, and locally estimated
      scatterplot smoothers (loess). A total of 3,088 patients with first IS were
      registered. Between 2000-2003 and 2012-2015, the age-adjusted incidence of IS
      decreased by 43% from 137.3 to 78.4/100,000/year (incidence rate ratio [IRR]
      0.57, 95% CI 0.5-0.64). Significant declines were observed in all subtypes,
      particularly in SVO (37.4-18; p < 0.0001) and less in CE (39.3-25; p < 0.0001).
      Reductions were recorded in males and females, younger (<55 years old) and older
      (>=55 years old) individuals, and white and black ethnic groups, though not
      significantly in the latter (144.6-116.2; p = 0.31 for IS). A 4-fold increase in
      prior-to-stroke use of statins was found (adjusted odds ratio [OR] 4.39, 95% CI
      3.29-5.86), and despite the increasing prevalence of hypertension (OR 1.54, 95%
      CI 1.21-1.96) and atrial fibrillation (OR 1.7, 95% CI 1.22-2.36), preventive use
      of antihypertensive and antiplatelet drugs was declining. A smaller number of
      participants in certain subgroup-specific analyses (e.g., black ethnicity and LAA
      subtype) could have limited the power to identify significant trends.
      CONCLUSIONS: The incidence of ISs has been declining since 2000 in all age groups
      but to a lesser extent in the black population. The reported changes in
      medication use are unlikely to fully explain the reduction in stroke incidence;
      however, innovative prevention strategies and better management of risk factors
      may contribute further reduction.

PMID- 30289920
TI  - Position effect, cryptic complexity, and direct gene disruption as disease
      mechanisms in de novo apparently balanced translocation cases.
AB  - The majority of apparently balanced translocation (ABT) carriers are
      phenotypically normal. However, several mechanisms were proposed to underlie
      phenotypes in affected ABT cases. In the current study, whole-genome mate-pair
      sequencing (WG-MPS) followed by Sanger sequencing was applied to further
      characterize de novo ABTs in three affected individuals. WG-MPS precisely mapped
      all ABT breakpoints and revealed three possible underlying molecular mechanisms.
      Firstly, in a t(X;1) carrier with hearing loss, a highly skewed X-inactivation
      pattern was observed and the der(X) breakpoint mapped ~87kb upstream an X-linked
      deafness gene namely POU3F4, thus suggesting an underlying long-range position
      effect mechanism. Secondly, cryptic complexity and a chromothripsis rearrangement
      was identified in a t(6;7;8;12) carrier with intellectual disability. Two
      translocations and a heterozygous deletion disrupted SOX5; a dominant nervous
      system development gene previously reported in similar patients. Finally, a
      direct gene disruption mechanism was proposed in a t(4;9) carrier with dysmorphic
      facial features and speech delay. In this case, the der(9) breakpoint directly
      disrupted NFIB, a gene involved in lung maturation and development of the pons
      with important functions in main speech processes. To conclude, in contrast to
      familial ABT cases with identical rearrangements and discordant phenotypes, where
      translocations are considered coincidental, translocations seem to be associated
      with phenotype presentation in affected de novo ABT cases. In addition, this
      study highlights the importance of investigating both coding and non-coding
      regions to decipher the underlying pathogenic mechanisms in these patients, and
      supports the potential introduction of low coverage WG-MPS in the clinical
      investigation of de novo ABTs.

PMID- 30289921
TI  - A biomechanical assessment of hydraulic ankle-foot devices with and without micro
      processor control during slope ambulation in trans-femoral amputees.
AB  - Slope ambulation is a challenge for trans-femoral amputees due to a relative lack
      of knee function. The assessment of prosthetic ankles on slopes is required for
      supporting the design, optimisation, and selection of prostheses. This study
      assessed two hydraulic ankle-foot devices (one of the hydraulic ankles is
      controlled by a micro-processor that allows real-time adjustment in ankle
      resistance and range of motion) used by trans-femoral amputees in ascending and
      descending a 5-degree slope walking, against a rigid ankle-foot device. Five
      experienced and active unilateral trans-femoral amputees performed ascending and
      descending slope tests with their usual prosthetic knee and socket fitted with a
      rigid ankle-foot, a hydraulic ankle-foot without a micro-processor, and a
      hydraulic ankle-foot with a micro-processor optimised for ascending and
      descending slopes. Peak values in hip, knee and ankle joint angles and moments
      were collected and the normalcy Trend Symmetry Index of the prosthetic ankle
      moments (as an indication of bio-mimicry) were calculated and assessment.
      Particular benefits of the hydraulic ankle-foot devices were better bio-mimicry
      of ankle resistance moment, greater range of motion, and improved passive
      prosthetic knee stability according to the greater mid-stance external knee
      extensor moment (especially in descending slope) compared to the rigid design.
      The micro-processor controlled device demonstrated optimised ankle angle and
      moment patterns for ascending and descending slope respectively, and was found to
      potentially further improve the ankle moment bio-minicry and prosthetic knee
      stability compared to the hydraulic device without a micro-processor. However the
      difference between the micro-processor controlled device and the one without a
      micro-processor does not reach a statistically significant level.

PMID- 30289922
TI  - Changes in the West African forest-savanna mosaic, insights from central Togo.
AB  - The West African forest-savanna mosaic, an important habitat for biodiversity and
      humans, is severely degraded, fragmented and modified by human activities.
      However, few studies have quantified the land cover changes observed over time
      and/or analysed the drivers of change. This study focused on Fazao-Malfakassa
      National Park, the largest in Togo, uses a combination of remote sensing, ground
      surveys and questionnaires to: (i) quantify vegetation changes, (ii) determine
      the drivers of change, (iii) compare results with findings elsewhere in the
      region and (iv) suggest management interventions. The images used were Landsat 5
      TM, Landsat 7 ETM and Sentinel-2. Different vegetation indices were computed
      including: number of fragments, index of dominance, mean area of a vegetation
      type and mean annual expansion rate. In total, 300 people (including park staff
      and local populations) were interviewed using a semi-structured questionnaire.
      Results indicate that between 1987 and 2015 closed-canopy forest and tree-savanna
      became severely degraded and fragmented, following trends in other parts of the
      West African forest-savanna mosaic. The main drivers of change were agricultural
      expansion, bush fires and timber extraction. Observed changes and drivers altered
      with time: e.g. agricultural expansion was greatest during 1987-2001 (linked with
      political instability) while illegal timber extraction augmented during 2001-2015
      (following increased timber value). Park staff and local populations' perceptions
      on drivers of change did not differ. Our study highlights that action is urgently
      needed if we are to preserve this important habitat, the biodiversity it hosts
      and the services it provides to humans. We suggest several management
      interventions, learning from successful interventions elsewhere in the region.

PMID- 30289923
TI  - Disparities in ratings of internal and external applicants: A case for model
      based inter-rater reliability.
AB  - Ratings are present in many areas of assessment including peer review of research
      proposals and journal articles, teacher observations, university admissions and
      selection of new hires. One feature present in any rating process with multiple
      raters is that different raters often assign different scores to the same
      assessee, with the potential for bias and inconsistencies related to rater or
      assessee covariates. This paper analyzes disparities in ratings of internal and
      external applicants to teaching positions using applicant data from Spokane
      Public Schools. We first test for biases in rating while accounting for measures
      of teacher applicant qualifications and quality. Then, we develop model-based
      inter-rater reliability (IRR) estimates that allow us to account for various
      sources of measurement error, the hierarchical structure of the data, and to test
      whether covariates, such as applicant status, moderate IRR. We find that
      applicants external to the district receive lower ratings for job applications
      compared to internal applicants. This gap in ratings remains significant even
      after including measures of qualifications and quality such as experience, state
      licensure scores, or estimated teacher value added. With model-based IRR, we
      further show that consistency between raters is significantly lower when rating
      external applicants. We conclude the paper by discussing policy implications and
      possible applications of our model-based IRR estimate for hiring and selection
      practices in and out of the teacher labor market.

PMID- 30289924
TI  - Parameter extraction method for the twisted pair cable with rectangular
      connectors.
AB  - Cables play an important role in transmitting energy and information. In this
      article, in order to obtain the S-parameters of the special twisted pair cable
      with rectangular connectors, a de-embedding method of the transmission matrix is
      proposed to deal with the two adapters ends of the cable. According to the
      frequency-dependent RLGC(f) model, the cable characteristics are extracted in the
      frequency range of 10 MHz to 200 MHz through conventional and modified methods
      respectively. The frequency-domain analysis shows that the inherent capacity of
      modified method can decrease the errors especially due to the discontinuities of
      hyperbolic functions. This research supplies an advantageous modelling approach
      for the cable to improve its robustness against disturbances in the S-parameters
      measurement that cannot be decreased with the calibration procedure.

PMID- 30289925
TI  - Corneal transplantation for Fuchs' endothelial dystrophy: A comparison of three
      surgical techniques concerning 10 year graft survival and visual function.
AB  - OBJECTIVE: Comparison of conventional Penetrating Keratoplasty (PKP), posterior
      mushroom PKP and Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK)
      regarding overall graft survival of primary corneal transplants for Fuchs'
      endothelial dystrophy (FED), best spectacle-corrected visual acuity (BSCVA) and
      astigmatism. METHODS: Single centre study using prospectively collected data from
      the national database for follow-up of corneal transplants. Main outcome
      parameters: 10 years graft survival, astigmatism at 24 months, pre- and post
      operative BSCVA. RESULTS: In total, 721 cases were included: PKP, n = 171;
      posterior mushroom PKP, n = 91; and DSAEK, n = 459. There was no significant
      difference in graft survival between PKP, posterior mushroom PKP and the DSAEK
      technique (log-rank test, P = 0.12). The overall post-operative BSCVA improvement
      in all treatment groups was significant (paired t-test, P<0.001). Pre-operative
      BSCVA was better for the DSAEK group (0.68 +/- 0.41 logMAR) as compared to the
      PKP (0.89 +/- 0.53) and posterior mushroom PKP group (0.90 +/- 0.58); ANOVA,
      P<0.001. After 24 months, BSCVA was significantly better for the DSAEK group
      (0.25 +/- 0.26 logMAR) compared to the PKP (0.35 +/- 0.29) and posterior mushroom
      PKP group (0.41 +/- 0.42); ANOVA, P<0.001. A significant difference in
      astigmatism was found (median test, P<0.001) between the DSAEK (1.7 +/- 1.1 D),
      PKP (4.6 +/- 2.7 D) and posterior mushroom PKP group (4.5 +/- 3.3 D). The
      significantly lower DSAEK-induced astigmatism was confirmed by vector analysis.
      CONCLUSION: There was no difference in graft survival and BSCVA improvement
      between conventional PKP, inverted mushroom PKP and DSAEK in this study. The
      significantly lower changes in astigmatism, wound stability and faster visual
      rehabilitation with DSAEK surgery are favourable aspects of this technique. The
      benefits of posterior lamellar keratoplasty warrant earlier intervention, which
      may contribute to preserve better vision for a prolonged period of remaining
      lifetime.

PMID- 30289926
TI  - Conceptual model for the health technology assessment of current and novel
      interventions in rheumatoid arthritis.
AB  - The objective of this study was to evaluate current approaches to economic
      modeling in rheumatoid arthritis (RA) and propose a new conceptual model for
      evaluation of the cost-effectiveness of RA interventions. We followed
      recommendations from the International Society of Pharmacoeconomics and Outcomes
      Research-Society of Medical Decision Making (ISPOR-SMDM) Modeling Good Research
      Practices Task Force-2. The process involved scoping the decision problem by a
      working group and drafting a preliminary cost-effectiveness model framework. A
      systematic literature review (SLR) of existing decision-analytic models was
      performed and analysis of an RA registry was conducted to inform the structure of
      the draft conceptual model. Finally, an expert panel was convened to seek input
      on the draft conceptual model. The proposed conceptual model consists of three
      separate modules: 1) patient characteristic module, 2) treatment module, and 3)
      outcome module. Consistent with the scope, the conceptual model proposed six
      changes to current economic models in RA. These changes proposed are to: 1) use
      composite measures of disease activity to evaluate treatment response as well as
      disease progression (at least two measures should be considered, one as the base
      case and one as a sensitivity analysis); 2) conduct utility mapping based on
      disease activity measures; 3) incorporate subgroups based on guideline
      recommended prognostic factors; 4) integrate realistic treatment patterns based
      on clinical practice/registry datasets; 5) assimilate outcomes that are not joint
      related (extra-articular outcomes); and 6) assess mortality based on disease
      activity. We proposed a conceptual model that incorporates the current
      understanding of clinical and real-world evidence in RA, as well as of existing
      modeling assumptions. The proposed model framework was reviewed with experts and
      could serve as a foundation for developing future cost-effectiveness models in
      RA.

PMID- 30289927
TI  - Clinical significance of the Kidney Donor Profile Index in deceased donors for
      prediction of post-transplant clinical outcomes: A multicenter cohort study.
AB  - BACKGROUND: We investigated whether the Kidney Donor Profile Index (KDPI) system
      is useful in predicting clinical outcomes in deceased donor kidney
      transplantation (DDKT). METHODS: Four hundred sixty-nine kidney transplant
      recipients (KTRs) receiving kidneys from 359 deceased donors were included in
      this study, which involved three transplant centers. KTRs were divided into high
      and low KDPI KTR groups based on the median KDPI score of 67%. We compared
      clinical outcomes between the high KDPI and low KDPI groups. RESULTS: There were
      no significant differences in the incidence of delayed graft function and acute
      rejection between high and low KDPI KTR groups. In comparison with histologic
      findings in allograft tissues obtained within three months from KT, the
      proportion of glomerulosclerosis was significantly higher in the high KDPI KTR
      group than in the low KDPI KTR group. With Kaplan-Meier analysis, the graft
      survival rate was significantly lower in the high KDPI KTR group than in the low
      KDPI KTR group (Log rank, P = 0.017), and multivariate analysis also demonstrated
      that a high KDPI score was a significant risk factor for death censored allograft
      failure (HR 2.62, 95% CI, 1.29-5.33, P = 0.008). CONCLUSION: The KDPI scoring
      system is useful in predicting allograft outcomes in a Korean DDKT cohort.

PMID- 30289928
TI  - Parenting behaviors that shape child compliance: A multilevel meta-analysis.
AB  - BACKGROUND: What are the parenting behaviors that shape child compliance? Most
      research on parent-child interactions relies on correlational research or
      evaluations of "package deal" interventions that manipulate many aspects of
      parenting at the same time. Neither approach allows for identifying the specific
      parenting behaviors that shape child compliance. To overcome this, we
      systematically reviewed and meta-analyzed available evidence on the effects of
      experimentally manipulated, discrete parenting behaviors-a niche in parent-child
      interaction research that contributes unique information on the specific
      parenting behaviors that shape child behavior. METHODS: We identified studies by
      systematically searching databases and through contacting experts. Nineteen
      studies (75 effect sizes) on four discrete parenting behaviors were included:
      praise, verbal reprimands, time-out, and ignore. In multilevel models, we tested
      for each parenting behavior whether it increased child compliance, including both
      observed and parent-reported measures of child compliance. RESULTS: Providing
      "time-out" for noncompliance robustly increased both observed and parent-reported
      child compliance (ds = 0.84-1.72; 95% CI 0.30 to 2.54). The same holds for
      briefly ignoring the child after non-compliance (ds = 0.36-1.77; 95% CI 0.04 to
      2.90). When observed and parent-reported outcomes were combined, but not when
      they were examined separately, verbal reprimands also increased child compliance
      (d = 0.72; 95% CI 0.26 to 1.19). Praise did not increase child compliance (ds = 
      0.27-1.19; 95% CI -2.04 to 1.59). CONCLUSION: Our findings suggest that of the
      discrete parenting behaviors that are experimentally studied in multiple trials,
      especially time-out and ignore, and to some extent verbal reprimands, shape child
      compliance.

PMID- 30289929
TI  - Aminoglycoside-inducible expression of the mexAB-oprM multidrug efflux operon in
      Pseudomonas aeruginosa: Involvement of the envelope stress-responsive AmgRS two
      component system.
AB  - Exposure of P. aeruginosa to the aminoglycoside (AG) paromomycin (PAR) induced
      expression of the PA3720-armR locus and the mexAB-oprM multidrug efflux operon
      that AmgR controls, although PAR induction of mexAB-oprM was independent of armR.
      Multiple AGs promoted mexAB-oprM expression and this was lost in the absence of
      the amgRS locus encoding an aminoglycoside-activated envelope stress-responsive 2
      component system (TCS). Purified AmgR bound to the mexAB-oprM promoter region
      consistent with this response regulator directly regulating expression of the
      efflux operon. The thiol-active reagent, diamide, which, like AGs, promotes
      protein aggregation and cytoplasmic membrane damage also promoted AmgRS-dependent
      mexAB-oprM expression, a clear indication that the MexAB-OprM efflux system is
      recruited in response to membrane perturbation and/or circumstances that lead to
      this. Despite the AG and diamide induction of mexAB-oprM, however, MexAB-OprM
      does not appear to contribute to resistance to these agents.

PMID- 30289930
TI  - Design and validation of an open-source modular Microplate Photoirradiation
      System for high-throughput photobiology experiments.
AB  - Research in photobiology is currently limited by a lack of devices capable of
      delivering precise and tunable irradiation to cells in a high-throughput format.
      This limits researchers to using expensive commercially available or custom-built
      light sources which make it difficult to replicate, standardize, optimize, and
      scale experiments. Here we present an open-source Microplate Photoirradiation
      System (MPS) developed to enable high-throughput light experiments in standard 96
      and 24-well microplates for a variety of applications in photobiology research.
      This open-source system features 96 independently controlled LEDs (4 LEDs per
      well in 24-well), Wi-Fi connected control and programmable graphical user
      interface (GUI) for control and programming, automated calibration GUI, and
      modular control and LED boards for maximum flexibility. A web-based GUI generates
      light program files containing irradiation parameters for groups of LEDs. These
      parameters are then uploaded wirelessly, stored and used on the MPS to run
      photoirradiation experiments inside any incubator. A rapid and semi-quantitative
      porphyrin metabolism assay was also developed to validate the system in wild-type
      fibroblasts. Protoporphyrin IX (PpIX) fluorescence accumulation was induced by
      incubation with 5-aminolevulinic acid (ALA), a photosensitization method
      leveraged clinically to destroy malignant cell types in a process termed
      photodynamic therapy (PDT), and cells were irradiated with 405nm light with
      varying irradiance, duration and pulsation parameters. Immediately after light
      treatment with the MPS, subsequent photobleaching was measured in live, adherent
      cells in both 96-well and a 24-well microplates using a microplate reader.
      Results demonstrate the utility and reliability of the Microplate
      Photoirradiation System to irradiate cells with precise irradiance and timing
      parameters in order to measure PpIx photobleaching kinetics in live adherent
      cells and perform comparable experiments with both 24 and 96 well microplate
      formats. The high-throughput capability of the MPS enabled measurement of enough
      irradiance conditions in a single microplate to fit PpIX fluorescence to a
      bioexponential decay model of photobleaching, as well as reveal a dependency of
      photobleaching on duty-cycle-but not frequency-in a pulsed irradiance regimen.

PMID- 30289931
TI  - Compound C inhibits nonsense-mediated RNA decay independently of AMPK.
AB  - The nonsense mediated RNA decay (NMD) pathway safeguards the integrity of the
      transcriptome by targeting mRNAs with premature translation termination codons
      (PTCs) for degradation. It also regulates gene expression by degrading a large
      number of non-mutant RNAs (including mRNAs and noncoding RNAs) that bear NMD
      inducing features. Consequently, NMD has been shown to influence development,
      cellular response to stress, and clinical outcome of many genetic diseases. Small
      molecules that can modulate NMD activity provide critical tools for understanding
      the mechanism and physiological functions of NMD, and they also offer potential
      means for treating certain genetic diseases and cancer. Therefore, there is an
      intense interest in identifying small-molecule NMD inhibitors or enhancers. It
      was previously reported that both inhibition of NMD and treatment with the AMPK
      selective inhibitor Compound C (CC) induce autophagy in human cells, raising the
      possibility that CC may be capable of inhibiting NMD. Here we show that CC indeed
      has a NMD-inhibitory activity. Inhibition of NMD by CC is, however, independent
      of AMPK activity. As a competitive ATP analog, CC does not affect the kinase
      activity of SMG1, an essential NMD factor and the only known kinase in the NMD
      pathway. However, CC treatment down-regulates the protein levels of several NMD
      factors. The induction of autophagy by CC treatment is independent of ATF4, a NMD
      target that has been shown to promote autophagy in response to NMD inhibition.
      Our results reveal a new activity of CC as a NMD inhibitor, which has
      implications for its use in basic research and drug development.

PMID- 30289932
TI  - Hypoxia/reperfusion predisposes to atherosclerosis.
AB  - Surgical interventions on blood vessels bear a risk for intimal hyperplasia and
      atherosclerosis as a consequence of injury. A specific feature of intimal
      hyperplasia is the loss of vascular smooth muscle cell (VSMC) differentiation
      gene expression. We hypothesized that immediate responses following injury induce
      vascular remodeling. To differentiate injury due to trauma, reperfusion and
      pressure changes we analyzed vascular responses to carotid artery bypass grafting
      in mice compared to transient ligation. As a control, the carotid artery was
      surgically laid open only. In both, bypass or ligation models, the inflammatory
      responses were transient, peaking after 6h, whereas the loss of VSMC
      differentiation gene expression persisted. Extended time kinetics showed that
      transient carotid artery ligation was sufficient to induce a persistent VSMC
      phenotype change throughout 28 days. Transient arterial ligation in ApoE knockout
      mice resulted in atherosclerosis in the transiently ligated vascular segment but
      not on the not-ligated contralateral side. The VSMC phenotype change could not be
      prevented by anti-TNF antibodies, Sorafenib, Cytosporone B or N-acetylcysteine
      treatment. Surgical interventions involving hypoxia/reperfusion are sufficient to
      induce VSMC phenotype changes and vascular remodeling. In situations of a
      perturbed lipid metabolism this bears the risk to precipitate atherosclerosis.

PMID- 30289933
TI  - Risk of malignant skin neoplasms in a cohort of workers occupationally exposed to
      ionizing radiation at low dose rates.
AB  - Recently an increasing trend in skin cancer rates has been observed in various
      populations including those exposed to different radiation types. Risk and dose
      response following prolonged radiation exposure remain unclear. The present study
      was aimed to assess skin melanoma (SM) and non-melanoma skin cancer (NMSC)
      incidence risks in a cohort of workers occupationally exposed to ionizing
      radiation at low dose rates over prolonged periods. The study cohort included
      workers of a Russian nuclear production facility, Mayak Production Association
      (PA), who were first employed in 1948-1982 and followed up till the end of 2013
      (the total of 22,377 individuals with 25% of females). Using AMFIT module of
      EPICURE software, relative risk and excess relative risk per unit dose (RR and
      ERR/Sv) were calculated. 60 SM and 294 NMSC cases were registered in members of
      the study cohort. SM and NMSC incidence was dependent on sex, attained age, age
      at first employment at the enterprise, type of facility, education level and was
      not dependent on calendar period of first employment, calendar period of
      diagnosis, duration of employment, smoking and alcohol consumption statuses. The
      risk of NMSC incidence was found to be significantly increased in workers
      occupationally exposed to ionizing radiation at cumulative doses above 2.0 Sv (RR
      = 2.52; 95% CI: 1.60, 3.97) compared to a reference dose category (0-0.05 Sv).
      NMSC incidence was found to be significantly associated with cumulative external
      gamma-dose with ERR/Sv of 0.49 (95% CI: 0.22, 0.90) without an adjustment for
      neutron dose and 0.51 (95% CI: 0.22, 0.93) while adjusted for neutron dose.
      Results of the analysis did not reveal a significant association of SM incidence
      with cumulative dose from external gamma-rays with ERR/Sv of 0.22 (95% CI: -0.29,
      1.46) not including a neutron dose adjustment and of 0.15 (95% CI: -0.41, 1.31)
      while adjusted for dose from neutron exposure.

PMID- 30289934
TI  - Quantitative spectral assessment of intracardiac electrogram characteristics
      associated with post infarct fibrosis and ventricular tachycardia.
AB  - BACKGROUND: Post-myocardial infarction (MI) remodeling contributes to increased
      electrophysiological and structural heterogeneity and arrhythmogenesis. Utilising
      the post-infarct ovine model our aim was to determine unipolar electrogram
      frequency characteristics consequent to this remodeling and the development of
      Ventricular Tachycardia (VT). METHODS AND RESULTS: Mapping studies were performed
      on 14 sheep at >1 month post-MI induction. Sheep were divided into VT inducible
      (n = 7) and non-inducible (n = 7) groups. Multielectrode needles (n = 20) were
      deployed within and surrounding ventricular scar for electrophysiological
      assessment of electrogram amplitude and width. Spectral analysis of electrograms
      was undertaken using wavelet and fast fourier transformations (WFFT) to calculate
      root mean square (RMS) power intervals spanning 0-300Hz in 20Hz intervals.
      Quantitative assessment between electrophysiological and histological parameters
      including collagen density, and structural organization of the myocardium was
      performed. Increasing myocardial scar density resulted in attenuation of
      electrogram amplitude and RMS values. (all p<0.01). Between groups there were no
      differences in electrogram amplitude (p = 0.37), however WFFT analysis revealed
      significantly higher RMS values in the VT group (p<0.05) in association with high
      frequency fractional components of the electrogram. As scar density increased,
      greater between-group differences in RMS were observed spanning this high
      frequency (200-280Hz) spectrum and which were proportionally dependent on the
      degree of structural disorganisation of the myocardium (p<0.001) and number of
      extrastimuli required to induce VT (p<0.05). CONCLUSION: High frequency unipolar
      electrogram spectral characteristics were quantitatively co-influenced by the
      presence of fibrosis and degree of myocardial structural dissorganisation and
      were associated with the propensity for development of VT.

PMID- 30289935
TI  - Health system measurement: Harnessing machine learning to advance global health.
AB  - BACKGROUND: Further improvements in population health in low- and middle-income
      countries demand high-quality care to address an increasingly complex burden of
      disease. Health facility surveys provide an important but costly source of
      information on readiness to provide care. To improve the efficiency of health
      system measurement, we applied unsupervised machine learning methods to assess
      the performance of the service readiness index (SRI) defined by the World Health
      Organization and compared it to empirically derived indices. METHODS: We drew
      data from nationally representative Service Provision Assessment surveys
      conducted in 10 countries between 2007 and 2015. We extracted 649 items in
      domains such as infrastructure, medication, and management to calculate an index
      using all available information and classified facilities into quintiles. We
      compared three approaches against the full item set: the SRI, a new index based
      on sequential backward selection, and an enriched SRI that added empirically
      selected items to the SRI. We evaluated index performance with a cross-validated
      kappa statistic comparing classification using the candidate index against the
      649-item index. RESULTS: 9238 facilities were assessed. The 49-item SRI performed
      poorly against the index using all 649 items, with a kappa value of 0.35. New
      empirically derived indices with 50 and 100 items captured much more information,
      with cross-validated kappa statistics of 0.71 and 0.80, respectively. Items
      varied across the indices and in sensitivity analyses. A 100-item enriched SRI
      reliably captured the information from the full index: 83% of the facilities were
      classified into correct quintiles of service readiness based on the full index.
      CONCLUSION: A facility readiness measure developed by global health experts
      performed poorly in capturing the totality of readiness information collected
      during facility surveys. Using a machine learning approach with sequential
      selection and cross-validation to identify the most informative items
      dramatically improved performance. Such approaches can make assessment of health
      facility readiness more efficient. Further improvements in measurement will
      require identification of external criteria-such as patient outcomes-to guide and
      validate measure development.

PMID- 30289936
TI  - Assessment of ecosystem services of an urbanized tropical estuary with a focus on
      habitats and scenarios.
AB  - Tropical estuaries are one of the most valuable ecosystems on the planet because
      of the number of ecosystem services they provide. The increasing anthropogenic
      pressure to which these estuaries are subject has caused a reduction in their
      natural capital stock. Therefore, the application of a pragmatic and rational
      ecosystem-based management approach to sustainably manage the multiple ecosystem
      services provided by this ecosystem is necessary. The aim of our study is to
      present an approach that combines prospective scenarios with habitat-based
      perspective to assess the supply capacity of ecosystem services, plus determine
      the impact of protected areas in an urbanized tropical estuary. The current
      situation and two scenarios were generated to evaluate the capacity of habitats
      to supply ecosystem services. This type of assessment will allow the decision
      makers to visualize the effect of their choices or the occurrence of events which
      might produce significant changes in the estuary. Thus, over time, measures can
      be taken to sustain the supply of ecosystem services. We determined that the
      establishment of protected areas have a positive impact; however, the effect is
      not the same for all of them. Consequently, indicating that actions such as
      community participation, research, education, management planning and
      infrastructure development must accompany the development of a protected area.

PMID- 30289937
TI  - "Is a picture really worth a thousand words?": A case study on classifying user
      attributes on Instagram.
AB  - Because using social media has become a major part of people's daily lives, many
      of their personal characteristics are often implicitly or explicitly reflected in
      the content they share. We present a study of two personal characteristics-age
      and gender-related to user engagement on Instagram that can be determined through
      the characterization of images and tags. We demonstrate the strong influence of
      age and gender on Instagram use in terms of topical and content differences. We
      then build age and gender classification models that yield F1 scores of up to 88%
      and 74% in the detection of age and gender, respectively, and that better
      characterize users by images than by tags. We further demonstrate the robustness
      of our models using a new set of test data, with which the models exhibit greater
      overall performance than human raters. Our study highlights that future research
      should look to exploit images to a greater degree because they complement text
      and there are many unexamined images with no embedded text available.

PMID- 30289938
TI  - Correction: Dissecting cancer heterogeneity based on dimension reduction of
      transcriptomic profiles using extreme learning machines.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0203824.].

PMID- 30289939
TI  - An agent-based model of urban insurgence: Effect of gathering sites and Koopman
      mode analysis.
AB  - The paper investigates the effect of preferential gathering sites on urban
      insurgency in an agent-based model (ABM). The ABM model was proposed in earlier
      work and has been validated using FBI data. There is a nonlinear tradeoff between
      the local density of citizens due to the number of preferential gathering sites
      and the ability of law enforcement officers (LEOs) to adequately patrol that
      leads to a non-monotonic behavior in the number of large scale outburst of
      insurgency with respect to the number of gathering sites. The inclusion of a
      moderate number of sites decreases the number of large-scale outbursts. Having no
      gathering sites or a large number of gathering sites has a dilutive effect on the
      number of large-scale outbursts. Thus, this non-monotonicity indicates that a
      small number of organized units produces a larger insurgency effect than a larger
      number of distributed units. It is also shown, using Koopman mode analysis, that
      the spatial morphology of agents due to the gathering sites gives rise to
      temporal organization of the model dynamics; there is a prominent quasi-periodic
      component in the number of active and intimidated citizens and in the spatial
      distribution of the LEOs.

PMID- 30289940
TI  - Correction: Willingness to pay and moral stance: The case of farm animal welfare
      in Germany.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0202193.].

PMID- 30289941
TI  - The aqueous extract of Phellinus igniarius (SH) ameliorates dextran sodium
      sulfate-induced colitis in C57BL/6 mice.
AB  - Phellinus igniarius, which is called Sanghuang in Chinese, is a fungal herb
      widely used in Traditional Chinese Medicine to treat stomachache, inflammation
      and tumors. Recent studies have demonstrated the antitumor, anti-diabetic, anti
      inflammatory and immunity-modulating activities of P. igniarius. In the present
      study, we investigated that ameliorating effect of the aqueous extract of P.
      igniarius fruiting body (SH) on dextran sodium sulfate (DSS)-induced colitis in
      C57BL/6 mice. Treatment with SH (250 and 400 mg/kg) for 8 weeks effectively
      alleviated the pathological indicators of colitis such as bodyweight reduction,
      disease activity index score, shortening of colon length and abnormal colon
      histology. The plasma levels of lipopolysaccharide (LPS) and inflammatory factors
      such as interleukin-6 (IL-6), IL-1beta and tumor necrosis factor (TNF)-alpha were
      all significantly reduced. Supplementation of SH (10 mg/L) also inhibited LPS
      elicited IL-1beta production by RAW264.7 macrophages. Real-time PCR and western
      blot showed that treatment with SH significantly inhibited the phosphorylation of
      nuclear factor kappa B inhibitor alpha (IkappaBalpha) and decreased the
      expression of IL-6/IL-1beta-maturation genes such as apoptosis-associated speck
      like protein (ASC3) and caspase-1 in the colon of DSS-induced colitis mice. These
      results suggest that SH is adequate for the treatment of colitis. Inhibiting the
      expression and release of inflammatory factors may participate in the colitis
      ameliorating effect of SH.

PMID- 30289942
TI  - Correction: Improved Control of Tuberculosis and Activation of Macrophages in
      Mice Lacking Protein Kinase R.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0030512.].

PMID- 30289943
TI  - Correction: Low-dose ionizing radiation exposure represses the cell cycle and
      protein synthesis pathways in in vitro human primary keratinocytes and U937 cell
      lines.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0199117.].

PMID- 30289944
TI  - Cancer increases the risk of atrial fibrillation during long-term follow-up
      (OPERA study).
AB  - INTRODUCTION: Relation between atrial fibrillation (AF) and cancer is known but
      not very well understood. The purpose of this prospective study was to find out
      whether subjects with cancer were at greater risk of AF than subjects without
      cancer. MATERIALS AND METHODS: The study was based on the OPERA (Oulu Project
      Elucidating Risk of Atherosclerosis) material and had 1045 subjects and the mean
      follow-up time of 16.3 years. During the follow-up AF and cancer diagnosis were
      made (atrial flutter included) if these events were listed in the National Death
      Registry and/or hospital discharge registry. RESULTS: In this study 130 subjects
      (12%) had cancer and 19% of these had AF, whereas only 9% of those without cancer
      experienced AF during the follow-up (p<0.001). Subjects in the cancer group had
      greater probability of developing atrial fibrillation during the follow-up time
      in comparison to the subjects without cancer (Hazard ratio (HR) 2.47 (95%CI) 1.57
      3.88) in multivariate model including relevant confounding factors. CONCLUSION:
      The main finding of this OPERA study was that cancer is an independent risk
      factor of atrial fibrillation. Still it remains unclear whether this association
      is causative or whether cancer and atrial fibrillation just share the same
      pathophysiologic mechanisms.

PMID- 30289946
TI  - Effects of climatically-modulated changes in solar radiation and wind speed on
      spring phytoplankton community dynamics in Lake Taihu, China.
AB  - Many studies have focused on the interactive effects of temperature increases due
      to global warming and nutrient enrichment on phytoplankton communities. Recently,
      non-temperature effects of climate change (e.g., decreases in wind speed and
      increases in solar radiation) on large lakes have received increasing attention.
      To evaluate the relative contributions of both temperature and non-temperature
      effects on phytoplankton communities in a large eutrophic subtropical shallow
      lake, we analyzed long-term monitoring data from Lake Taihu, China from 1997 to
      2016. Results showed that Lake Taihu's spring phytoplankton biovolume and
      composition changed dramatically over this time frame, with a change in dominant
      species. Stepwise multiple linear regression models indicated that spring
      phytoplankton biovolume was strongly influenced by total phosphorus (TP), light
      condition, wind speed and total nitrogen (TN) (radj2 = 0.8, p < 0.01). Partial
      redundancy analysis (pRDA) showed that light condition accounted for the greatest
      variation of phytoplankton community composition, followed by TP and wind speed,
      as well as the interactions between TP and wind speed. Our study points to the
      additional importance of non-temperature effects of climate change on
      phytoplankton community dynamics in Lake Taihu.

PMID- 30289945
TI  - Impact of current smoking on 2-year clinical outcomes between durable-polymer
      coated stents and biodegradable-polymer-coated stents in acute myocardial
      infarction after successful percutaneous coronary intervention: Data from the
      KAMIR.
AB  - OBJECTIVE: Data concerning the effect of current smoking on solely new-generation
      drug-eluting stents (DES) are limited. We investigated the impact of current
      smoking on 2-year clinical outcomes between durable-polymer (DP)-coated DES
      (zotarolimus-eluting [ZES] and everolimus eluting [EES]) and biodegradable
      polymer (BP)-coated biolimus-eluting stent (BES) in acute myocardial infarction
      (AMI) patients after successful percutaneous coronary intervention (PCI).
      METHODS: Finally, a total of 8357 AMI patients with current smoking underwent
      successful PCI with new-generation DES (ZES, EES, and BES) were enrolled and
      divided into three groups as ZES (n = 3199), EES (n = 3987), and BES group (n =
      1171). The primary endpoint was the occurrence of major adverse cardiac events
      (MACE) defined as all-cause death (cardiac death [CD] or non-cardiac death),
      recurrent AMI (re-MI), any revascularization (target lesion revascularization
      [TLR], target vessel revascularization [TVR], and non-TVR). The secondary
      endpoint was the incidence of definite or probable stent thrombosis (ST).
      RESULTS: The 2-year adjusted hazard ratio (HR) of MACE for ZES vs. EES (1.055;
      95% confidence interval [CI], 0.843-1.321; p = 0.638), ZES vs. BES (HR, 0.885;
      95% CI, 0.626-1.251; p = 0.488), EES vs. BES (HR, 0.889; 95% CI, 0.633-1.250; p =
      0.499), and ZES/EES vs. BES (HR, 0.891; 95% CI, 0.648-1.126; p = 0.480) were
      similar. The occurrence of ST after adjustment were also comparable. In addition,
      the 2-year adjusted HR for all-cause death, CD, re-MI, TLR, TVR, and non-TVR were
      not different. CONCLUSIONS: In this study, DP-DES and BP-DES showed comparable
      safety and efficacy during 2-year follow-up periods. Therefore, DP-DES or BP-DES
      are equally acceptable in AMI patients with current smoking undergoing PCI.

PMID- 30289947
TI  - Burn injury alters the intestinal microbiome's taxonomic composition and
      functional gene expression.
AB  - Burn patients have a high risk of sepsis-related mortality even after surviving
      the initial injury. Immunosuppression increases the risk of sepsis after burn
      injury, as does the disruption of the intestinal epithelial barrier, which allows
      the translocation of bacteria and bacterial products into the circulation. The
      integrity of the intestinal epithelial barrier is largely maintained by the
      intestinal microbiota. Burn injury has been reported to result in significant
      changes in the intestinal microbiome composition. In this mouse study, we confirm
      these taxonomic differences in a full-thickness scald injury model using CF-1
      mice. For the first time, we also address alterations in functional gene
      expression of the intestinal microbiota after burn injury to assess the
      microbiome's physiological capabilities for overgrowth and pathogenic invasion:
      38 pathways were differentially abundant between the sham and burn injury mice,
      including bacterial invasion of epithelial cells and gap- and adherens junction
      pathways.

PMID- 30289948
TI  - Correction: Stereotyping across intersections of race and age: Racial
      stereotyping among White adults working with children.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0201696.].

PMID- 30289949
TI  - Correction: Duration of physical activity, sitting, sleep and the risk of total
      knee replacement among Chinese in Singapore, the Singapore Chinese Health Study.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0202554.].

PMID- 30289950
TI  - Lp-PLA2, scavenger receptor class B type I gene (SCARB1) rs10846744 variant, and
      cardiovascular disease.
AB  - BACKGROUND: We previously reported association of SCARB1 SNP rs10846744 with
      common carotid IMT (cIMT) and cardiovascular disease (CVD) events. Since
      rs10846744 has been reported in association with Lp-PLA2 mass and activity, we
      hypothesized that inflammatory pathways might mediate the association of
      rs10846744 with atherosclerosis. METHODS: We first examined association of
      rs10846744 in CVD in multiple large-scale consortium-based genome-wide
      association studies. We further examined 27 parameters of interest, including Lp
      PLA2 mass and activity, inflammatory markers, and plasma phospholipid fatty
      acids, and fatty acid ratios in participants from the Multi-Ethnic Study of
      Atherosclerosis (MESA), as potential mediators in the pathway linking rs10846744
      with cIMT and incident CVD. Finally, we examined the association of rs10846744
      with Lp-PLA2 activity, cardiovascular outcomes, and interaction with the Lp-PLA2
      inhibitor, darapladib, in the Stabilization of Atherosclerotic Plaque by
      Initiation of Darapladib Therapy (STABILITY) and Stabilization of Plaque using
      Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID-TIMI 52) studies.
      RESULTS: SCARB1 rs10846744 was associated with coronary artery disease events in
      CARDIoGRAMplusC4D (odds ratio 1.05; 95% CI [1.02, 1.07]; P = 1.4x10-4). In
      combined analysis across race/ethnic groups in MESA, rs10846744 was associated
      with Lp-PLA2 mass (P = 0.04) and activity (P = 0.001), homocysteine (P = 0.03),
      LDL particle number (P = 0.01), docosahexaenoic acid [DHA] (P = 0.01),
      docosapentaenoic acid [DPA] (P = 0.04), DPA/ eicosapentaenoic acid [EPA] ratio (P
      = 0.002), and DHA/EPA ratio (P = 0.008). Lp-PLA2 activity was identified as a
      mediator of rs10846744 with cIMT in a basic model (P = 8x10-5), but not after
      adjustment for CVD risk factors. There was no interaction or modifier effect of
      the Lp-PLA2 inhibitor darapladib assignment on the relationship between
      rs10846744 and major CVD events in either STABILITY or SOLID-TIMI 52. SUMMARY:
      SCARB1 rs10846744 is significantly associated with Lp-PLA2 activity,
      atherosclerosis, and CVD events, but Lp-PLA2 activity is not a mediator in the
      association of rs10846744 with cIMT in MESA.

PMID- 30289952
TI  - Smoking-induced control of miR-133a-3p alters the expression of EGFR and HuR in
      HPV-infected oropharyngeal cancer.
AB  - PURPOSE: Human papillomavirus (HPV) infected oropharyngeal squamous cell
      carcinoma (OPSCC) patients have a better prognosis compared to HPV(-)
      counterparts. However, a subset of HPV(+) patients with a smoking history fail to
      respond to the standard of care treatments such as radiation and chemotherapy. To
      understand the underlying mechanism driving HPV(+) OPSCC patient resistance to
      treatment and recurrence, we sought to identify and characterize the
      differentially expressed miRNAs and their target genes in HPV(+) smokers and non
      smokers. EXPERIMENTAL DESIGN: MicroRNA expression analysis was performed using
      Nanostring in tumor tissues isolated from a prospective cohort of HPV(+) smoking
      (n = 9) and HPV(+) (n = 13) non-smoking OPSCC patients. Identified miRNAs of
      interest were further validated using qRT-PCR in cigarette smoke extract (CSE)
      treated HPV(+) and E6/E7 overexpressing HPV(-) cells. RESULTS: In comparison to
      OPSCC HPV(+) non-smokers, 38 miRNAs were significantly altered in the HPV(+)
      smoker patients cohort and out of that 9 were downregulated. Altered miRNA
      expression was also detected in the serum and metastatic lymph nodes of HPV(+)
      smokers versus non-smokers. Expression of miR-133a-3p was significantly
      downregulated in OPSCC smokers, HPV(+) cells and E6/E7 overexpressing HPV(-)
      cells treated with CSE. Reduction of miR-133a-3p induced the upregulation of miR
      133a-3p target mRNAs EGFR and HuR. CONCLUSIONS: Our results indicate that miR
      133a-3p is a target of smoking-induced changes in HPV(+) patients and alters the
      expression of EGFR and HuR which may promote HPV associated oropharyngeal cancer.
      Therefore, future treatment strategies for HPV(+) OPSCC smokers should focus on
      EGFR inhibition and the development of selective therapies to target HuR.

PMID- 30289953
TI  - Cu/Zn-superoxide dismutase forms fibrillar hydrogels in a pH-dependent manner via
      a water-rich extended intermediate state.
AB  - Under certain conditions, amyloid-like fibrils can develop into three-dimensional
      networks and form hydrogels by a self-assembly process. When Cu/Zn superoxide
      dismutase (SOD1), an anti-oxidative enzyme, undergoes misfolding, fibrillar
      aggregates are formed, which are a hallmark of a certain form of familial
      amyotrophic lateral sclerosis (ALS). However, the issue of whether SOD1 fibrils
      can be assembled into hydrogels remains to be tested. Here, we show that the SOD1
      polypeptides undergo hydrogelation accompanied by the formation of thioflavin T
      positive fibrils at pH 3.0 and 4.0, but not at pH 5.0 where precipitates are
      formed. The results of viscoelastic analyses indicate that the properties of SOD1
      hydrogels (2%) were similar to and slightly more fragile than a 0.25% agarose
      gel. In addition, monitoring by a quartz crystal microbalance with admittance
      analysis showed that the denaturing of immobilized SOD1 on a sensor under the
      hydrogelation conditions at pH 3.0 and 4.0 resulted in an increase in the
      effective acoustic thickness from ~3.3 nm (a folded rigid form) to ~50 and ~100
      nm (an extended water-rich state), respectively. In contrast, when SOD1 was
      denatured under the same conditions at pH 5.0, a compact water-poor state with an
      effective acoustic thickness of ~10 nm was formed. The addition of physiological
      concentrations of NaCl to the pH 4.0 sample induced a further extension of the
      SOD1 with larger amounts of water molecules (with an effective acoustic thickness
      of ~200 nm) but suppressed hydrogel formation. These results suggest that
      different denatured intermediate states of the protein before self-assembly play
      a major role in determining the characteristics of the resulting aggregates and
      that a conformational change to a suitable level of extended water-rich
      intermediate state before and/or during intermolecular assembling is required for
      fibrillation and hydrogelation in the case of globular proteins.

PMID- 30289955
TI  - Variation in susceptibility of eight insecticides in the brown planthopper
      Nilaparvata lugens in three regions of Vietnam 2015-2017.
AB  - The brown planthopper (BPH), Nilaparvata lugens, is a serious threat to rice
      production in Vietnam and insecticides are widely used for its control. Migration
      of the BPH have one of its roots in tropical Vietnam in the Mekong River Delta
      and the insecticide resistance status of BPH populations from Vietnam is thus
      important for East Asia. In the present investigation, we evaluate the
      susceptibility of BPH populations from nine provinces from the Red River Delta,
      the Central Coastal region and the Mekong River Delta of eight insecticides
      during 2015-17. BPH field populations of Vietnam have developed a low to moderate
      level of resistance to the neonicotinoids dinotefuran, nitenpyram and
      imidacloprid, the pyrethroid etofenprox, the anticholinesterase fenobucarb, as
      well as fipronil and pymetrozine, and the growth regulator buprofezin. There was
      a correlation of in toxicology of fipronil, dinotefuran, etofenprox, buprofezin,
      which represents four different modes of action. The neonicotinoid nitenpyram,
      pymetrozine and fenobucarb did not show correlation in toxicology to any of the
      investigated insecticides. For most insecticides, a gradient of susceptibility
      was established from the Red River Delta in the north, through the Central
      Coastal region and to the Mekong River Delta in the south of Vietnam. The most
      susceptible populations were from the north. Insecticide resistance of the BPH
      populations in Vietnam is not at an alarming level and they are not the direct
      origin of high insecticide resistance found in East Asia. The cross-resistance
      pattern of BPH populations in Vietnam, where insecticides with different modes of
      action correlated, indicate that insecticides should be used with caution. There
      could be a buildup of a general metabolic resistance, which alone or in
      combination with the emergence of target-site resistance mutations will cause
      control problems. The results will be beneficial for development of resistance
      management strategies to prevent and delay development of insecticide resistance
      in BPH not only for Vietnam, but also for more northern Asian regions due the
      migration of BPH from tropical Vietnam.

PMID- 30289954
TI  - Dual biomarkers long non-coding RNA GAS5 and microRNA-34a co-expression signature
      in common solid tumors.
AB  - Accumulating evidence indicates that non-coding RNAs including microRNAs (miRs)
      and long non-coding RNAs (lncRNAs) are aberrantly expressed in cancer, providing
      promising biomarkers for diagnosis, prognosis and/or therapeutic targets. We
      aimed in the current work to quantify the expression profile of miR-34a and one
      of its bioinformatically selected partner lncRNA growth arrest-specific 5 (GAS5)
      in a sample of Egyptian cancer patients, including three prevalent types of
      cancer in our region; renal cell carcinoma (RCC), glioblastoma (GB), and
      hepatocellular carcinoma (HCC) as well as to correlate these expression profiles
      with the available clinicopathological data in an attempt to clarify their roles
      in cancer. Quantitative real-time polymerase chain reaction analysis was applied.
      Different bioinformatics databases were searched to confirm the potential miRNAs
      lncRNA interactions of the selected ncRNAs in cancer pathogenesis. The tumor
      suppressor lncRNA GAS5 was significantly under-expressed in the three types of
      cancer [0.08 (0.006-0.38) in RCC, p <0.001; 0.10 (0.003-0.89) in GB, p < 0.001;
      and 0.12 (0.015-0.74) in HCC, p < 0.001]. However, levels of miR-34a greatly
      varied according to the tumor type; it displayed an increased expression in RCC
      [4.05 (1.003-22.69), p <0.001] and a decreased expression in GB [0.35 (0.04
      0.95), p <0.001]. Consistent to the computationally predicted miRNA-lncRNA
      interaction, negative correlations were observed between levels of GAS5 and miR
      34a in RCC samples (r = -0.949, p < 0.001), GB (r = -0.518, p < 0.001) and HCC (r
      = -0.455, p = 0.013). Kaplan-Meier curve analysis revealed that RCC patients with
      down-regulated miR-34a levels had significantly poor overall survival than their
      corresponding (p < 0.05). Hierarchical clustering analysis showed RCC patients
      could be clustered by GAS5 and miR-34a co-expression profile. Our results suggest
      potential applicability of GAS5 and miR-34a with other conventional markers for
      various types of cancer. Further functional validation studies are warranted to
      confirm miR-34a/GAS5 interplay in cancer.

PMID- 30289951
TI  - Pathologic findings and causes of death of stranded cetaceans in the Canary
      Islands (2006-2012).
AB  - This study describes the pathologic findings and most probable causes of death
      (CD) of 224 cetaceans stranded along the coastline of the Canary Islands (Spain)
      over a 7-year period, 2006-2012. Most probable CD, grouped as pathologic
      categories (PCs), was identified in 208/224 (92.8%) examined animals. Within
      natural PCs, those associated with good nutritional status represented 70/208
      (33.6%), whereas, those associated with significant loss of nutritional status
      represented 49/208 (23.5%). Fatal intra- and interspecific traumatic interactions
      were 37/208 (17.8%). Vessel collisions included 24/208 (11.5%).
      Neonatal/perinatal pathology involved 13/208 (6.2%). Fatal interaction with
      fishing activities comprised 10/208 (4.8%). Within anthropogenic PCs, foreign
      body-associated pathology represented 5/208 (2.4%). A CD could not be determined
      in 16/208 (7.7%) cases. Natural PCs were dominated by infectious and parasitic
      disease processes. Herein, our results suggest that between 2006 and 2012, in the
      Canary Islands, direct human activity appeared responsible for 19% of cetaceans
      deaths, while natural pathologies accounted for 81%. These results, integrating
      novel findings and published reports, aid in delineating baseline knowledge on
      cetacean pathology and may be of value to rehabilitators, caregivers,
      diagnosticians and future conservation policies.

PMID- 30289957
TI  - Pharmaceutical Marketing at the 2018 American Geriatrics Society Annual
      Scientific Meeting: The Case of Noctiva and the Need for Increased Vigilance.

PMID- 30289958
TI  - Successful Prehabilitation: A Noble Goal.

PMID- 30289956
TI  - Base excess is superior to lactate-levels in prediction of ICU mortality after
      cardiac surgery.
AB  - INTRODUCTION: Cardiac surgery with the use of cardiopulmonary bypass is known to
      induce distinct metabolic changes. Respective changes in acid-base status
      including increased systemic lactate levels were previously related to clinical
      outcomes, but data remain controversial. Therefore, we aim to investigate the
      relevance of lactate and base excess (BE) levels on ICU-mortality in patients
      admitted to the ICU after cardiac surgery. MATERIALS AND METHODS: Perioperative
      data of patients treated in a tertiary care academic center admitted to the ICU
      after on-pump surgery were analyzed in a retrospective fashion. Receiver
      operation characteristic (ROC) curves were constructed for admission lactate
      levels and BE with calculation of optimal cut-off values to predict ICU
      mortality. Univariate followed by multivariate regression models were constructed
      to identify potential outcome-relevant indices. RESULTS: Data from 1,058 patients
      were included in the analysis. Area under the curves for prediction of ICU
      mortality were 0.79 for lactate levels at ICU admission (sensitivity 61.9%/
      specificity 87.5%; optimal cut-off level 3.9mmol/l), and 0.7 for BE (sensitivity
      52.4%/ specificity 93.8%, optimal cut-off level -6.7), respectively. Multivariate
      regression identified BE < -6.7 as the single metabolic predictor of ICU
      mortality (HR 4.78, 95%-CI 1.4-16.33, p = 0.01). Explorative subgroup analyses
      revealed that the combination of lactate <=3.9mmol/l and BE <= -6.7 has stronger
      impact on mortality than a combination of lactate of >3.9mmol/l and BE > -6.7 (HR
      2.56, 95%-CI 0.18-37.17). CONCLUSIONS: At ICU-admission, severely reduced BE
      appears superior to hyperlactatemia with regard to prediction of ICU-mortality in
      patients after cardiac surgery.

PMID- 30289959
TI  - Serum Cholesterol and Incident Alzheimer's Disease: Findings from the Adult
      Changes in Thought Study.
AB  - OBJECTIVES: To evaluate associations between high-density lipoprotein cholesterol
      (HDL) and non-HDL-C levels at specific ages and subsequent Alzheimer's disease
      (AD) risk. DESIGN: Prospective population-based cohort study. SETTING: Adult
      Changes in Thought (ACT) Study. PARTICIPANTS: Individuals aged 65 and older with
      no dementia at ACT Study entry. We identified separate, partially overlapping
      subcohorts of ACT participants who were eligible for each age band-specific
      analysis (50-59, n = 1,088; 60-69, n = 2,852; 70-79, n = 2,344; 80-89, n = 537).
      MEASUREMENTS: Exposure consisted of clinical measures of total cholesterol (TC)
      and HDL-C from laboratory data during a given age band. Outcomes of incident AD
      were assessed post-age band using standard research diagnostic criteria.
      Statistical analyses used adjusted Cox proportional hazards regression models for
      each exposure and outcome pair within an age band. Cholesterol exposures were
      modeled using cubic splines. RESULTS: For non-HDL-C, we found a statistically
      significant association with AD risk in the 60 to 69 (omnibus p = .005) and 70 to
      79 (omnibus p = .04) age bands, suggesting a potential U-shaped relationship
      (greater risk at low and high levels). For example, in people aged 60 to 69,
      those with an average non-HDL-C level of 120 mg/DL had a 29% greater AD hazard
      (hazard ratio (HR)=1.29, 95% confidence interval (CI)=1.04-1.61) than those with
      an average non-HDL-C level of 160 mg/dL, whereas those with an average non-HDL-C
      level of 210 mg/dL had a 16% greater hazard (HR=1.16, 95% CI=1.01-1.33). We did
      not find a statistically significant association between HDL-C and AD risk.
      CONCLUSION: People with low (120 mg/dL) and high (210 mg/dL) non-HDL-C levels
      during their 60s and 70s had modestly higher risk of AD than those with
      intermediate (160 mg/dL) levels. The extreme age bands (50s and 80s) had small
      sample sizes.

PMID- 30289960
TI  - Reply to Comment on "Personality Changes During the Transition from Cognitive
      Health to Mild Cognitive Impairment".
AB  - This letter comments on the letter by Luis Aguera-Ortiz et al.

PMID- 30289961
TI  - Medical Costs for Osteoporosis-Related Fractures in High-Risk Medicare
      Beneficiaries.
AB  - OBJECTIVES: To estimate the incremental direct medical care costs associated with
      first fracture observable in high-risk older adults. DESIGN: Retrospective
      analysis of claims and survey data over a 3-year period from the Health and
      Retirement Study (HRS), a nationally representative biennial study of individuals
      aged 50 and older. SETTING: United States. PARTICIPANTS: Participants were HRS
      respondents who consented to have their Medicare claims data linked to the HRS
      data, were aged 65 or older, had at least 1 risk factor for fracture observable
      in the data, and experienced a fracture between 1996 and 2008 (n = 689) and their
      propensity score-matched controls (n = 689). MEASUREMENTS: Total Medicare,
      inpatient, outpatient, emergency department, physician office visit, and
      prescription drug care expenditures were primary outcomes. Two-staged generalized
      linear models were estimated using a difference-in-differences model. RESULTS:
      Fracture cases' total Medicare expenditures increased by $13,929 (95% confidence
      interval (CI)=$11,920-15,938, p <.001) more than those of matched controls from
      the year before the index or fracture date to 1 year after the index date.
      Inpatient expenditures of $12,751 (95% CI=$10,790-14,7111, p < .001) more for
      fracture cases than comparison cases primarily drove this increase. Two and 3
      years after fracture, there were no significant differences in growth in
      expenditures between the two groups. Results did not vary according to whether
      the fracture was at the hip or other site. CONCLUSION: Fractures impose a
      significant economic burden, especially in the first year after the fracture, in
      Medicare beneficiaries with at least 1 risk factor for fracture. Our sample was
      limited to community-dwelling individuals, and we are unable to control for
      fracture history before the study period. Costs may be greater for those in
      skilled nursing and similar facilities and for those who have had a previous
      fracture.

PMID- 30289962
TI  - Comment on "Personality Changes During the Transition from Cognitive Health to
      Mild Cognitive Impairment".

PMID- 30289963
TI  - Mass Incarceration in an Aging America: Implications for Geriatric Care and Aging
      Research.

PMID- 30289964
TI  - Inhibition of NF-kappaB improves sensitivity to irradiation and EGFR-TKIs and
      decreases irradiation-induced lung toxicity.
AB  - Resistance to radiotherapy and to EGFR tyrosine kinase inhibitors (EGFR-TKIs), as
      well as therapy-related lung toxicity, are serious problems in the treatment of
      lung cancer. NF-kappaB has been reported to be associated with radioresistance.
      Therefore, we evaluated its effects on sensitivity to irradiation and to EGFR
      TKIs; irradiation-induced lung toxicity; and the effects of irradiation on
      sensitivity to EGFR-TKIs. We used IKKbeta inhibitor IMD 0354 or p65 depletion to
      explore their effects on sensitivity to irradiation and to EGFR-TKIs in vitro and
      in vivo. We evaluated the efficacy of IMD 0354 in a radiation-induced pulmonary
      fibrosis mouse model. Irradiation enhanced activation and expression of MET and
      therefore suppressed the sensitivity of lung cancer cells to irradiation or EGFR
      TKIs. Inhibition of NF-kappaB by IMD 0354 or by p65 depletion reversed
      irradiation-induced MET activation and increased the sensitivity of lung cancer
      cells to irradiation, to EGFR-TKIs and to the combination thereof in vitro and in
      vivo. In addition, IMD 0354 significantly reduced lung toxicity in a murine model
      of irradiation-induced pneumonia and lung fibrosis. These findings indicated that
      NF-kappaB inhibition can improve sensitivity to irradiation and to EGFR-TKIs and
      can decrease irradiation-induced lung toxicity in lung cancer.

PMID- 30289965
TI  - Salvage surgery for squamous cell carcinoma of the head and neck in the era of
      immunotherapy: Is it time to clarify our guidelines?

PMID- 30289967
TI  - The Mechanisms of Alpha-Amylase Inhibition by Flavan-3-Ols and the Possible
      Impacts of Drinking Green Tea on Starch Digestion.
AB  - Many studies have shown that flavan-3-ols inhibit mammalian alpha-amylases but
      the published IC50 and Ki values vary up to a thousand times. We therefore tested
      the effects of 6 pure flavan-3-ols-abundant in green tea-on the activity of pure
      porcine pancreatic alpha-amylase (PPA) under steady-state kinetic conditions. We
      used both amylose and maltopentaose as substrates, along with spectrophotometry
      and chromatography as analytical tools, respectively. A Docking approach was also
      used to probe the interaction between PPA and each flavan-3-ol. The results
      showed that the 6 flavan-3-ols inhibit amylose hydrolysis with Ki comprised
      between 7 and 34 MUM, according to a mixed inhibition profile for gallocatechin
      gallate, and a competitive inhibition profile for the 5 other flavanols. Only the
      galloyl-containing flavan-3-ols inhibited the maltopentaose hydrolysis with a Ki
      of about 30 MUM according to a noncompetitive profile. We conclude that dietary
      flavan-3-ols could inhibit starch digestion nonnegligibly. The results of the
      docking trials were concordant with the kinetic data and have noticeably revealed
      that the cis-flavan-3-ols epigallocatechin gallate and epicatechin gallate bind
      similarly to PPA, involving pi-stacking with Trp59.

PMID- 30289969
TI  - Hospital Readmission Risk for Patients with Self-Reported Hearing Loss and
      Communication Trouble.

PMID- 30289966
TI  - Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in
      salivary duct carcinoma: Implications for targeted therapy.
AB  - BACKGROUND: Patients with advanced primary and recurrent salivary duct carcinoma
      (SDC), a rare and lethal malignancy, have limited therapeutic options. Novel
      small-molecule agents aimed at targeting critical signaling associated with SDC
      tumorigenesis may lead to new therapeutic options for patients with these tumors.
      The human epidermal growth factor receptor 2 (HER2)/phosphoinositide 3-kinase
      (PI3K) axis, an important oncogenic pathway, has been targeted for therapy in
      several solid tumors. Currently, little is known about the role and clinical
      implications of alterations of the HER2/PI3K pathway in patients with SDC.
      METHODS: The authors investigated the clinicopathologic features, genetic
      alterations, and expression of key members of the HER2/PI3K pathway in 43 primary
      tumors and conducted in vitro functional and targeted drug-response analyses on
      cell lines derived from salivary epithelial carcinomas. RESULTS: In primary
      tumors, loss of phosphatase and tensin homolog (PTEN) expression was identified
      in 22 of 43 tumors (51%), overexpression of HER2 was observed in 12 of 43 tumors
      (28%), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
      (PIK3CA) mutations were identified in 12 of 43 tumors (28%). Phosphorylated
      protein kinase B (p-AKT) was highly expressed in most tumors. Most tumors (70%)
      displayed mutually exclusive alterations of PI3K members, whereas 8 tumors (19%)
      had 2 or more concurrent abnormalities. In vitro studies demonstrated a direct
      association between PTEN loss and PI3K pathway activation and evidence of
      response to combined PI3Kalpha and PI3Kbeta and/or pan-PI3K inhibitors.
      CONCLUSIONS: The current analyses reveal frequent PTEN loss and mutually
      exclusive alterations of key PI3K pathway members in SDC and demonstrate in vitro
      evidence of a response to pan-PI3K inhibitors. These results provide a framework
      for a biomarker-based substratification of patients with SDC in future targeted
      therapy. Cancer 2018;124:3523-32. (c) 2018 American Cancer Society.

PMID- 30289968
TI  - Increasing Advance Care Planning Using a Surgical Optimization Program for Older
      Adults.
AB  - OBJECTIVES: To describe an innovative model of care, the Surgery Wellness Program
      (SWP), that uses a multidisciplinary team to develop and implement preoperative
      care plans for older adults, and its effect on engagement in advance care
      planning (ACP). DESIGN: Retrospective analysis of clinical demonstration project.
      SETTING: Preoperative optimization program for older adults undergoing surgery at
      a 796-bed academic tertiary hospital. PARTICIPANTS: Older adults (N=131) who
      participated in the SWP from February 2015 to August 2017. INTERVENTION: All SWP
      participants met with a geriatrician who engaged them in a semistructured ACP
      discussion. Trained medical and nurse practitioner students were used as health
      coaches who contacted participants regularly to address and document ACP.
      MEASUREMENTS: Self-report of ACP engagement before and after participation in the
      SWP was determined using SWP geriatrician and health coach progress notes.
      Medical records were examined for scanned documentation. Feasibility data on
      number of health coach calls were collected. RESULTS: After completion of the
      program, the proportion of participants with a designated surrogate increased
      from 67% to 78% (p<.001), completed advance directive (AD) from 51% to 72%
      (p<.001), and an AD scanned into the medical record from 14% to 60% (p<.001).
      Participants who underwent surgery received a median of 4 health coaching calls
      over a median of 27 days between their clinic visit and surgery. Case examples
      are presented to highlight how the SWP attends to the many components of the ACP
      process. CONCLUSION: Preoperative optimization programs provide a unique
      opportunity to engage older adults in ACP.

PMID- 30289970
TI  - Low Clinical Trial Accrual of Patients With Myelodysplastic Syndromes: Causes and
      Potential Solutions.
AB  - Despite few effective therapies, only a small percentage of patients diagnosed
      with myelodysplastic syndromes (MDS) in the United States are enrolled in
      prospective, interventional clinical trials. MDS-specific barriers to trial
      accrual include a high frequency of elderly patients with comorbid conditions,
      atypical disease features and uncertainty regarding the diagnosis (because other
      nonclonal processes also can cause dysplasia and cytopenias), a history of
      another nonmyeloid neoplasm resulting in therapy-related MDS, rapid disease
      recurrence after allogeneic stem cell transplantation, and an arbitrary division
      between MDS and acute myeloid leukemia. In addition, barriers to accrual that are
      common to other oncology populations, such as difficulty traveling to clinical
      trial enrollment sites and narrow trial eligibility criteria, also prevent
      patients with MDS from enrolling in studies. Collectively these barriers must be
      assessed systematically, and creative solutions are needed to improve outcomes
      for this needy patient population.

PMID- 30289971
TI  - Association between treatment of superficial bladder cancer and 10-year mortality
      in older adults with multiple chronic conditions.
AB  - BACKGROUND: Multiple chronic conditions (MCC) are common among older patients
      with cancer; however, the exclusion of these patients from clinical trials has
      resulted in scarce knowledge concerning outcomes, resulting in variations in
      treatment. Superficial bladder cancer (SBC) disproportionately affects older
      adults, yet to the authors' knowledge few studies to date have examined whether
      treatment improves long-term survival. In the current study, the authors
      evaluated the association between treatment of SBC and 10-year mortality in
      medically complex older adults. METHODS: The authors identified 1800 older (aged
      >=60 years) patients with SBC (American Joint Committee on Cancer stage <=I) from
      2 community-based health systems who received treatment (bladder instillation
      and/or transurethral resection) or observation. Cox proportional hazards
      regression was performed adjusting for age, sex, race, health system, stage of
      disease/grade, and MCC (>=2 baseline chronic conditions). Propensity score
      analysis using stabilized inverse probability of treatment weights was used to
      compare 10-year mortality in the 2 treatment groups with adjustment for
      covariates. RESULTS: Overall, 1485 patients (82.5%) and 315 patients (17.5%)
      received treatment and observation, respectively. In unweighted multivariable
      analysis, treatment was associated with a 30% reduction in death (adjusted hazard
      ratio [HR], 0.70; 95% confidence interval [95% CI], 0.58-0.85 [P<.01]) and MCC
      with a 72% increase in death (adjusted HR, 1.72; 95% CI, 1.44-2.05 [P<.01]).
      Weighted analysis with adjustment (doubly robust) also demonstrated a survival
      benefit for treatment (adjusted HR, 0.66; 95% CI, 0.52-0.84 [P<.01]).
      CONCLUSIONS: The results of the current study demonstrated a clinically
      meaningful association between cancer treatment and survival benefit in older,
      medically complex patients with SBC, even after adjustment for medical
      complexity. These data provide a foundation for future work aimed at
      personalizing the treatment guidance of older patients with cancer with MCC.

PMID- 30289973
TI  - CINP is a novel cofactor of KLF5 required for its role in the promotion of cell
      proliferation, survival and tumor growth.
AB  - Kruppel-like factor 5 (KLF5) both suppresses and promotes tumor growth depending
      on cellular context. The mechanisms underlying tumor promotion could be
      targetable for therapy. Although a number of transcriptional targets of KLF5 have
      been identified and implicated in KLF5-mediated tumor growth, how KLF5 regulates
      these genes remains to be addressed. Here we performed coimmunoprecipitation (co
      IP) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the TSU-Pr1
      bladder cancer cell line, in which KLF5 is shown to promote tumor growth, to
      identify KLF5-interacting nuclear proteins that are necessary for KLF5's tumor
      promoting function. LC-MS/MS revealed 122 potential KLF5 binding proteins in the
      nuclear proteins precipitated by the KLF5 antibody, and the top nine candidates
      included AHNAK, TFAM, HSDL2, HNRNPC, CINP, IST1, FBL, PABPC1 and SNRNP40. SRB
      assays of these nine proteins indicated that silencing CINP had the most potent
      inhibitory effect on cell growth in KLF5-expressing cells but did not affect
      parental TSU-Pr1 cells. Further analyses not only confirmed the physical
      interaction between KLF5 and CINP, also demonstrated that knockdown of CINP
      attenuated the effects of KLF5 on cell cycle progression, apoptosis and
      tumorigenesis. Silencing CINP also attenuated the effect of KLF5 on the
      expression of a number of genes and signaling pathways, including cell cycle
      regulator Cyclin D1 and apoptosis-related Caspase 7. These results suggest that
      CINP is a cofactor of KLF5 that is crucial for the promotion of tumor growth, and
      that the KLF5-CINP interaction could be a novel therapeutic target for inhibiting
      KLF5-promoted tumor growth.

PMID- 30289972
TI  - Transient receptor potential ankyrin 1 (TRPA1) plays a critical role in a mouse
      model of cancer pain.
AB  - There is a major, unmet need for the treatment of cancer pain, and new targets
      and medicines are required. The transient receptor potential ankyrin 1 (TRPA1), a
      cation channel expressed by nociceptors, is activated by oxidizing substances to
      mediate pain-like responses in models of inflammatory and neuropathic pain. As
      cancer is known to increase oxidative stress, the role of TRPA1 was evaluated in
      a mouse model of cancer pain. Fourteen days after injection of B16-F10 murine
      melanoma cells into the plantar region of the right hind paw, C57BL/6 mice
      exhibited mechanical and thermal allodynia and thigmotaxis behavior. While heat
      allodynia was partially reduced in TRP vanilloid 1 (TRPV1)-deficient mice,
      thigmotaxis behavior and mechanical and cold allodynia were absent in TRPA1
      deficient mice. Deletion of TRPA1 or TRPV1 did not affect cancer growth.
      Intrathecal TRPA1 antisense oligonucleotides and two different TRPA1 antagonists
      (HC-030031 or A967079) transiently attenuated thigmotaxis behavior and mechanical
      and cold allodynia. A TRPV1 antagonist (capsazepine) attenuated solely heat
      allodynia. NADPH oxidase activity and hydrogen peroxide levels were increased in
      hind paw skin 14 days after cancer cell inoculation. The antioxidant, alpha
      lipoic acid, attenuated mechanical and cold allodynia and thigmotaxis behavior,
      but not heat allodynia. Whereas TRPV1, via an oxidative stress-independent
      pathway, contributes partially to heat hypersensitivity, oxidative stress
      dependent activation of TRPA1 plays a key role in mediating thigmotaxis behavior
      and mechanical and cold allodynia in a cancer pain model. TRPA1 antagonists might
      be beneficial in the treatment of cancer pain.

PMID- 30289974
TI  - Reduced expression of the ferroptosis inhibitor glutathione peroxidase-4 in
      multiple sclerosis and experimental autoimmune encephalomyelitis.
AB  - Glutathione peroxidase 4 (GPx4) is the only enzyme capable of reducing toxic
      lipid hydroperoxides in biological membranes to the corresponding alcohols using
      glutathione as the electron donor. GPx4 is the major inhibitor of ferroptosis, a
      non-apoptotic and iron-dependent programmed cell death pathway, which has been
      shown to occur in various neurological disorders with severe oxidative stress. In
      this study, we investigate whether GPx4 expression is altered in multiple
      sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE).
      The results clearly show that mRNA expression for all three GPx4 isoforms
      (cytoplasmic, mitochondrial and nuclear) decline in multiple sclerosis gray
      matter and in the spinal cord of MOG35-55 peptide-induced EAE. The amount of GPx4
      protein is also reduced in EAE, albeit not in all cells. Neuronal GPx4
      immunostaining, mostly cytoplasmic, is lower in EAE spinal cords than in control
      spinal cords, while oligodendrocyte GPx4 immunostaining, mainly nuclear, is
      unaltered. Neither control nor EAE astrocytes and microglia cells show GPx4
      labeling. In addition to GPx4, two other negative modulators of ferroptosis
      (gamma-glutamylcysteine ligase and cysteine/glutamate antiporter), which are
      critical to maintain physiological levels of glutathione, are diminished in EAE.
      The decrease in the ability to eliminate hydroperoxides was also evidenced by the
      accumulation of lipid peroxidation products and the reduction in the proportion
      of the docosahexaenoic acid in non-myelin lipids. These findings, along with
      presence of abnormal neuronal mitochondria morphology, which includes an
      irregular matrix, disrupted outer membrane and reduced/absent cristae, are
      consistent with the occurrence of ferroptotic damage in inflammatory
      demyelinating disorders.

PMID- 30289976
TI  - Proteomics of neurodegenerative diseases: analysis of human post-mortem brain.
AB  - Dementias are prevalent brain disorders in the aged population. Dementias pose
      major socio-medical burden, but currently there is no cure available. Novel
      proteomics approaches hold promise to identify alterations of the brain proteome
      that could provide clues on disease etiology, and identify candidate proteins to
      develop further as a biomarker. In this review, we focus on recent proteomics
      findings from brains affected with Alzheimer's Disease, Parkinson Disease
      Dementia, Frontotemporal Dementia, and Amyotrophic Lateral Sclerosis. These
      studies confirmed known cellular changes, and in addition identified novel
      proteins that may underlie distinct aspects of the diseases.

PMID- 30289975
TI  - The impact of obesity and bariatric surgery on circulating and tissue biomarkers
      of endometrial cancer risk.
AB  - Obesity is the strongest risk factor for endometrial cancer (EC). To inform
      targeted screening and prevention strategies, we assessed the impact of obesity
      and subsequent bariatric surgery-induced weight loss on endometrial morphology
      and molecular pathways implicated in endometrial carcinogenesis. Blood and
      endometrial tissue were obtained from women with class III-IV obesity (body mass
      index >=40 and >=50 kg/m2 , respectively) immediately prior to gastric bypass or
      sleeve gastrectomy, and at two and 12 months' follow up. The endometrium
      underwent pathological examination and immunohistochemistry was used to quantify
      proliferation (Ki-67), oncogenic signaling (PTEN, pAKT, pERK) and hormone
      receptor (ER, PR) expression status. Circulating biomarkers of insulin
      resistance, reproductive function and inflammation were also measured at each
      time point. Seventy-two women underwent bariatric surgery. At 12 months, the mean
      change in total and excess body weight was -32.7 and -62.8%, respectively.
      Baseline endometrial biopsies revealed neoplastic change in 10 women (14%): four
      had EC, six had atypical hyperplasia (AH). After bariatric surgery, most cases of
      AH resolved (5/6) without intervention (3/6) or with intrauterine progestin
      (2/6). Biomarkers of endometrial proliferation (Ki-67), oncogenic signaling
      (pAKT) and hormone receptor status (ER, PR) were significantly reduced, with
      restoration of glandular PTEN expression, at 2 and 12 months. There were
      reductions in circulating biomarkers of insulin resistance (HbA1c, HOMA-IR) and
      inflammation (hsCRP, IL-6), and increases in reproductive biomarkers (LH, FSH,
      SHBG). We found an unexpectedly high prevalence of occult neoplastic changes in
      the endometrium of women undergoing bariatric surgery. Their spontaneous reversal
      and accompanying down-regulation of PI3K-AKT-mTOR signaling with weight loss may
      have implications for screening, prevention and treatment of this disease.

PMID- 30289977
TI  - Thioridazine inhibits autophagy and sensitizes glioblastoma cells to
      temozolomide.
AB  - Glioblastoma multiforme (GBM) has a poor prognosis with an overall survival of 14
      15 months following surgery, radiation and chemotherapy using temozolomide (TMZ).
      A major problem is that the tumors acquire resistance to therapy. In an effort to
      improve the therapeutic efficacy of TMZ, we performed a genome-wide RNA
      interference (RNAi) synthetic lethality screen to establish a functional gene
      signature for TMZ sensitivity in human GBM cells. We then queried the
      Connectivity Map database to search for drugs that would induce corresponding
      changes in gene expression. By this approach we identified several potential
      pharmacological sensitizers to TMZ, where the most potent drug was the
      established antipsychotic agent Thioridazine, which significantly improved TMZ
      sensitivity while not demonstrating any significant toxicity alone.
      Mechanistically, we show that the specific chemosensitizing effect of
      Thioridazine is mediated by impairing autophagy, thereby preventing adaptive
      metabolic alterations associated with TMZ resistance. Moreover, we demonstrate
      that Thioridazine inhibits late-stage autophagy by impairing fusion between
      autophagosomes and lysosomes. Finally, Thioridazine in combination with TMZ
      significantly inhibits brain tumor growth in vivo, demonstrating the potential
      clinical benefits of compounds targeting the autophagy-lysosome pathway. Our
      study emphasizes the feasibility of exploiting drug repurposing for the design of
      novel therapeutic strategies for GBM. This article is protected by copyright. All
      rights reserved.

PMID- 30289979
TI  - Landscape heterogeneity strengthens the relationship between beta-diversity and
      ecosystem function.
AB  - Consensus has emerged in the literature that increased biodiversity enhances the
      capacity of ecosystems to perform multiple functions. However, most
      biodiversity/ecosystem function studies focus on a single ecosystem, or on
      landscapes of homogenous ecosystems. Here, we investigate how increased landscape
      level environmental dissimilarity may affect the relationship between different
      metrics of diversity (alpha, beta, or gamma) and ecosystem function. We produced
      a suite of simulated landscapes, each of which contained four experimental
      outdoor aquatic mesocosms. Differences in temperature and nutrient conditions of
      the mesocosms allowed us to simulate landscapes containing a range of within
      landscape environmental heterogeneities. We found that the variation in ecosystem
      functions was primarily controlled by environmental conditions, with diversity
      metrics accounting for a smaller (but significant) amount of variation in
      function. When landscapes were more homogeneous, alpha, beta, and gamma diversity
      was not associated with differences in primary production, and only gamma was
      associated with changes in decomposition. In these homogeneous landscapes,
      differences in these two ecosystem functions were most strongly related to
      nutrient and temperature conditions in the ecosystems. However, as landscape
      level environmental dissimilarity increased, the relationship between alpha,
      beta, or gamma and ecosystem functions strengthened, with beta being a greater
      predictor of variation in decomposition at the highest levels of environmental
      dissimilarity than alpha or gamma. We propose that when all ecosystems in a
      landscape have similar environmental conditions, species sorting is likely to
      generate a single community composition that is well suited to those
      environmental conditions, beta is low, and the efficiency of diversity-ecosystem
      function couplings is similar across communities. Under this low beta, the effect
      of abiotic conditions on ecosystem function will be most apparent. However, when
      environmental conditions vary among ecosystems, species sorting pressures are
      different among ecosystems, producing different communities among locations in a
      landscape. These conditions lead to stronger relationships between beta and the
      magnitude of ecosystem functions. Our results illustrate that abiotic conditions
      and the homogeneity of communities influence ecosystem function expressed at the
      landscape scale.

PMID- 30289978
TI  - LKB1 regulates PRMT5 activity in breast cancer.
AB  - Protein arginine methyltransferase 5 (PRMT5) is the main enzyme responsible for
      the symmetrical dimethylation of arginine residues on target proteins in both the
      cytoplasm and the nucleus. Though its activity has been associated with tumor
      progression in various cancers, the expression pattern of this oncoprotein has
      been scarcely studied in breast cancer. In the current work, we analyzed its
      expression in a large cohort of breast cancer patients, revealing higher nuclear
      PRMT5 levels in ERalpha-positive tumors and an association with prolonged disease
      free and overall survival. Interestingly, high PRMT5 nuclear expression was also
      associated with higher nuclear liver kinase B1 (LKB1), suggesting that a
      functional relationship may occur. Consistently, several approaches provided
      evidence that PRMT5 and LKB1 interact directly in the cytoplasm of mammary
      epithelial cells. Moreover, although PRMT5 is not able to methylate LKB1, we
      found that PRMT5 is a bona fade substrate for LKB1. We identified T132, 139 and
      144 residues, located in the TIM-Barrel domain of PRMT5, as target sites for LKB1
      phosphorylation. The point mutation of PRMT5 T139/144 to A139/144 drastically
      decreased its methyltransferase activity, due probably to the loss of its
      interaction with regulatory proteins such as MEP50, pICln and RiOK1. In addition,
      modulation of LKB1 expression modified PRMT5 activity, highlighting a new
      regulatory mechanism that could have clinical implications.

PMID- 30289980
TI  - What Do Transplant Physicians Think About Palliative Care? A National Survey
      Study.
AB  - BACKGROUND: Despite its established benefits, palliative care (PC) is rarely
      utilized for hematopoietic stem cell transplant (HSCT) patients. We sought to
      examine transplant physicians' perceptions of PC. METHODS: We conducted a cross
      sectional survey of transplant physicians recruited from the American-Society-for
      Blood-and-Marrow-Transplantation. Using a 28-item questionnaire adapted from
      prior studies, we examined physicians' access to PC services, and perceptions of
      PC. We computed a composite score of physicians' attitudes about PC (mean = 16.9,
      SD = 3.37) and explored predictors of attitudes using a linear mixed model.
      RESULTS: 277/1005 (28%) of eligible physicians completed the questionnaire. The
      majority (76%) stated that they trust PC clinicians to care for their patients,
      but 40% felt that PC clinicians do not have enough understanding to counsel HSCT
      patients about their treatments. Most endorsed that when patients hear the term
      PC, they feel scared (82%) and anxious (76%). Nearly half (46%) reported that the
      service name 'palliative care' is a barrier to utilization. Female sex (beta =
      0.85, P = .024), having <10 years of clinical practice (beta = 1.39, P = .004),
      and perceived quality of PC services (beta = 0.60, P < .001) were all associated
      with a more positive attitude towards PC. Physicians with a higher sense of
      ownership over their patients' PC issues (beta = -0.36, P < .001) were more
      likely to have a negative attitude towards PC. CONCLUSIONS: The majority of
      transplant physicians trust PC, but have substantial concerns about PC
      clinicians' knowledge about HSCT and patients' perception of the term 'palliative
      care'. Interventions are needed to promote collaboration, improve perceptions,
      and enhance integration of PC for HSCT recipients.

PMID- 30289981
TI  - Therapeutic activity of DCC-2036, a novel tyrosine kinase inhibitor, against
      triple-negative breast cancer patient-derived xenografts by targeting AXL/MET.
AB  - Triple-negative breast cancer (TNBC) is insensitive to endocrine therapies and
      targeted therapies to human epidermal growth factor receptor-2 (HER2), estrogen
      receptor (ER) and progesterone receptor (PR). New targets and new targeted
      therapeutic drugs for TNBC are desperately needed. Our study confirmed that DCC
      2036 inhibited the proliferation, invasion, migration and epithelial-mesenchymal
      transition (EMT) of TNBC cells as well as induced apoptosis. Moreover, the
      antiproliferative activity of DCC-2036 was more efficient than that of most
      clinical drugs. In addition, the combination of DCC-2036 and cisplatin or
      lapatinib had synergistic effects on TNBC cells. Mechanistically, DCC-2036
      targeted AXL/MET, especially AXL, and regulated the downstream PI3K/Akt-NFkappaB
      signaling to exert its antitumor effect in TNBC. DCC-2036 also inhibited the
      growth and metastasis of xenografted MDA-MB-231 cells (AXL/MET-high TNBC cells)
      but not MDA-MB-468 cells (AXL-low TNBC cells) in NSG mice in vivo. Furthermore,
      DCC-2036 significantly inhibited tumor growth and invasion of AXL/MET-high TNBC
      PDX tumors but not AXL/MET-low TNBC PDX tumors. These results highlighted the
      roles of AXL/MET in cancer growth and metastasis and further verified that the
      critical targets of DCC-2036 are AXL and MET, especially AXL. In addition, there
      was no significant toxicity of DCC-2036 even at a high dosage. Therefore, DCC
      2036 may be a potential compound to treat TNBC, especially for tumors with
      AXL/MET overexpression.

PMID- 30289982
TI  - PNPLA3 and TM6SF2 variants as risk factors of hepatocellular carcinoma across
      various etiologies and severity of underlying liver diseases.
AB  - Few single nucleotide polymorphisms (SNPs) have been reproducibly associated with
      hepatocellular carcinoma (HCC). Our aim was to test the association between nine
      SNPs and HCC occurrence. SNPs in genes linked to HCC (DEPDC5, GRIK1, KIF1B,
      STAT4, MICA, DLC1, DDX18) or to liver damage (PNPLA3-rs738409, TM6SF2-rs58542926)
      in GWAS were genotyped in discovery cohorts including 1,020 HCC, 2,021 controls
      with chronic liver disease and 2,484 healthy individuals and replication was
      performed in prospective cohorts of cirrhotic patients with alcoholic liver
      disease (ALD, n = 249) and hepatitis C (n = 268). In the discovery cohort, PNPLA3
      and TM6SF2 SNPs were associated with HCC (OR = 1.67 [CI95%:1.16-2.40], p = 0.005;
      OR = 1.45 [CI95%:1.08-1.94], p = 0.01) after adjustment for fibrosis, age, gender
      and etiology. In contrast, STAT4-rs7574865 was associated with HCC only in HBV
      infected patients (p = 0.03) and the other tested SNP were not linked with HCC
      risk. PNPLA3 and TM6SF2 variants were independently associated with HCC in
      patients with ALD (OR = 3.91 [CI95%:2.52-6.06], p = 1.14E-09; OR = 1.79
      [CI95%:1.25-2.56], p = 0.001) but not with other etiologies. PNPLA3 SNP was also
      significantly associated with HCC developed on a nonfibrotic liver (OR = 2.19
      [CI95%:1.22-3.92], p = 0.007). The association of PNPLA3 and TM6SF2 with HCC risk
      was confirmed in the prospective cohort with ALD. A genetic score including
      PNPLA3 and TM6SF2 minor alleles showed a progressive significant increased risk
      of HCC in ALD patients. In conclusion, PNPLA3-rs738409 and TM6SF2-rs58542926 are
      inherited risk variants of HCC development in patients with ALD in a dose
      dependent manner. The link between PNPLA3 and HCC on nonfibrotic liver suggests a
      direct role in liver carcinogenesis.

PMID- 30289984
TI  - When Asymptomatic Bacteriuria is not Asymptomatic or "Pseudo-Urinary Tract
      Infection".

PMID- 30289985
TI  - Reply to: When Asymptomatic Bacteriuria Is Not Asymptomatic or "Pseudo-Urinary
      Tract Infection".

PMID- 30289983
TI  - International neural monitoring study group guideline 2018 part I: Staging
      bilateral thyroid surgery with monitoring loss of signal.
AB  - This publication offers modern, state-of-the-art International Neural Monitoring
      Study Group (INMSG) guidelines based on a detailed review of the recent
      monitoring literature. The guidelines outline evidence-based definitions of
      adverse electrophysiologic events, especially loss of signal, and their
      incorporation in surgical strategy. These recommendations are designed to reduce
      technique variations, enhance the quality of neural monitoring, and assist
      surgeons in the clinical decision-making process involved in surgical management
      of recurrent laryngeal nerve. The guidelines are published in conjunction with
      the INMSG Guidelines Part II, Optimal Recurrent Laryngeal Nerve Management for
      Invasive Thyroid Cancer-Incorporation of Surgical, Laryngeal, and Neural
      Electrophysiologic Data. Laryngoscope, 128:S1-S17, 2018.

PMID- 30289986
TI  - Functional and phenotypic heterogeneity of Th17 cells in health and disease.
AB  - BACKGROUND: Th17 cells have nonredundant roles in maintaining immunity,
      particularly at mucosal surfaces. These roles are achieved principally through
      the production of cytokines and the recruitment of other immune cells to maintain
      the integrity of mucosal barriers and prevent the dissemination of
      microorganisms. Th17 cells are heterogeneous and exhibit a considerable degree of
      plasticity. This allows these cells to respond to changing environmental
      challenges. However, Th17 cells also play pro-inflammatory roles in chronic
      autoimmune diseases. The trigger(s) that initiate these Th17 responses in chronic
      autoimmune diseases remain unclear. DESIGN: In this report, we provide an
      overview of studies involving animal models, patient data, genome wide
      association studies and clinical trials targeting IL-17 for treatment of patients
      to gain a better understanding of the pathogenic roles of Th17 cells play in a
      range of autoimmune diseases. RESULTS: The report sheds light on likely triggers
      that initiate or perpetuate Th17 responses that promote chronic inflammation and
      autoimmunity. The divergent effects of tumour necrosis factor alpha blockade on
      Th17 cells in patients, is explored. Furthermore, we highlight the role of Th17
      cells in inducing autoreactive B cells, leading to autoantibody production.
      Pathogenic bacterial species can change Th17 cell phenotype and responses. These
      findings provide insights into how Th17 cells could be induced to promoting
      autoimmune disease pathogenesis. CONCLUSION: This article provides an overview of
      the distinct roles Th17 cells play in maintaining immunity at mucosal surfaces
      and in skin mucosa and how their functional flexibility could be linked with
      chronic inflammation in autoimmune rheumatic diseases.

PMID- 30289987
TI  - Visions of Eye Commensals: The Known and the Unknown About How the Microbiome
      Affects Eye Disease.
AB  - Until recently, the ocular surface is thought by many to be sterile and devoid of
      living microbes. It is now becoming clear that this may not be the case. Recent
      and sophisticated PCR analyses have shown that microbial DNA-based "signatures"
      are present within various ethnic, geographic, and contact lens wearing
      communities. Furthermore, using a mouse model of ocular surface disease, we have
      shown that the microbe, Corynebacterium mastitidis (C. mast), can stably colonize
      the ocular mucosa and that a causal relationship exists between ocular C. mast
      colonization and beneficial local immunity. While this constitutes proof-of
      concept that a bona fide ocular microbiome that tunes immunity can exist at the
      ocular surface, there remain numerous unanswered questions to be addressed before
      microbiome-modulating therapies may be successfully developed. Here, the authors
      will briefly outline what is currently known about the local ocular microbiome as
      well as microbiomes associated with other sites, and how those sites may play a
      role in ocular surface immunity. Understanding how commensal microbes affect the
      ocular surface immune homeostasis has the potential revolutionize how we think
      about treating ocular surface disease.

PMID- 30289988
TI  - Dielectrophoretic manipulation of nanomaterials: A review.
AB  - Nanomaterials manipulation using dielectrophoresis (DEP) is one of the major
      research areas that could potentially benefit the micro/nano science for diverse
      applications, such as microfluidics, nanomachine, and biosensor. The innovation
      and development of basic theories, methods or applications will have a huge
      impact on the entire related field. Specifically, for DEP manipulation of
      nanomaterials, improvements in comprehensive performance of accuracy, flexibility
      and scale could promote broader applications in micro/nano science. Therefore, to
      explore the directions for future research, this paper critically provides an
      overview on the fundamentals, recent progress, current challenges, and potential
      applications of DEP manipulation of nanomaterials. This review will also act as a
      guide and reference for researchers to explore promising applications in relevant
      research.

PMID- 30289989
TI  - Impact of all-oral direct-acting antivirals on clinical and economic outcomes in
      chronic hepatitis C patients in the U.S.
AB  - : Approved treatment for hepatitis C virus (HCV) with all-oral direct acting
      antivirals (DAA) therapy is now entering into its fourth year; however, little
      has been reported on the real world clinical [decompensated cirrhosis (DCC) and
      hepatocellular carcinoma (HCC)] and economic outcomes. A retrospective cohort
      analysis of the Truven Health MarketScan Database (2012 - 2016) was conducted. In
      a cohort of 26,105 newly diagnosed HCV patients, 30% received all-oral DAA
      therapy (DAA group) and 70% were not treated (untreated group). Multivariate Cox
      proportional hazards models were used to compare the risk of developing HCC and
      DCC, stratified by cirrhosis status. Among cirrhotic patients (n=2,157), DAA
      therapy was associated with a 72% and a 62% lower incidence of HCC (hazard ratio
      (HR): 0.28; 95% confidence interval (CI):0.15-0.52) and DCC (HR: 0.38; 95% CI:
      0.26-0.56). Similarly, DAA therapy was associated with a 57% and a 58% lower
      incidence of HCC (HR: 0.43; 95% CI:0.26-0.71) and DCC (HR: 0.42; 95% CI: 0.30
      0.58) in non-cirrhotic HCV patients (n=23,948). A propensity-score matched cohort
      of 8,064 HCV-infected patients who had at least a 12-month follow-up after HCV
      treatment was included for economic analysis. For cirrhotic patients in the DAA
      group, the mean adjusted liver-related costs ($1,749 vs $4,575; P<0.001) and all
      cause medical costs ($19,300 vs $33,039; P<0.001) were significantly lower
      compared to those in the untreated group. The mean adjusted costs were not
      statistically different between the two groups among non-cirrhotic patients.
      CONCLUSIONS: In the short term, all-oral DAA treatment for HCV infection was
      associated with a decreased risk of developing HCC and DCC resulting in decreased
      healthcare costs, especially in cirrhotic patients. A longitudinal study is
      necessary to confirm our findings. This article is protected by copyright. All
      rights reserved.

PMID- 30289991
TI  - Proton pump inhibitors use and risk of hepatocellular carcinoma.
AB  - One cohort study using the Taiwan's database conducted by Kao et al published in
      Hepatology reported that proton pump inhibitors use was not associated with the
      risk of developing hepatocellular carcinoma in patients with chronic hepatitis B
      infection or chronic hepatitis C infection. The findings were compatible with our
      cohort analysis using the Taiwan's database showing no association between proton
      pump inhibitors use and hepatocellular carcinoma. In contrast, a recent case
      control study using the Taiwan's database conducted by Shao et al reported that
      proton pump inhibitors use might increase the risk of hepatocellular carcinoma in
      patients without hepatitis B infection or hepatitis C infection (odds ratio 2.86,
      95% confidence interval 2.69-3.04). This article is protected by copyright. All
      rights reserved.

PMID- 30289990
TI  - The effect of 20-week continuous 60 Hz magnetic field exposure on testicular
      function in sprague-dawley rats.
AB  - Accumulating evidence does not yet confirm the effect of power line frequency
      magnetic field (MF) on human health and fertility. We recently reported that, at
      continuous 60 Hz MF exposure in mice, the dose given as magnetic flux density
      (tesla; T) and duration of exposure was related to induce testicular germ cell
      apoptosis. We aimed to characterize the effect of a 20-week continuous exposure
      to 60 Hz MF on the motility, morphology, and number of sperm as well as the
      apoptosis of testicular germ cell in rats. Sprague-Dawley rats were exposed for
      20 weeks to 60 Hz MF of 2, 20, or 200 MUT for 24 h/day with rats exposed to sham
      conditions, serving as the control. The exposure to 60 Hz MF of 2 and 20 MUT had
      no effects on testicular in this study. The exposure to 60 Hz MF of 200 MUT for
      20 weeks induced increases of the apoptotic cells (P < 0.001) in germ cells and
      decreases of sperm numbers (P < 0.05). However, the MF did not significantly
      affect the body or testis mass, seminiferous tubule diameter, or the motility or
      morphology of sperm. This study concluded that exposure to 60 Hz MF of 200 MUT
      can increase testicular germ cell apoptosis, especially spermatogonia, and reduce
      sperm count. Also compared to previous mice studies, rats are less sensitive than
      mice to exposure to 60 Hz MF. Bioelectromagnetics. 39:539-546, 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 30289992
TI  - Proton pump inhibitors are associated to minimal and overt hepatic encephalopathy
      and increase mortality in cirrhotics.
AB  - BACKGROUND: Minimal hepatic encephalopathy (MHE) is a subclinical cognitive
      impairment frequently observable in cirrhotics. Proton pump inhibitors (PPIs) can
      contribute to small-bowel bacterial overgrowth but no study investigated the link
      between PPIs and MHE. AIM: to investigate the relationship between minimal HE and
      PPIs use as well as the role of PPIs use in the development of overt HE and
      survival. PATIENTS AND METHODS: 310 consecutive cirrhotic patients were included
      in the study and followed up for 14.1+/-12.3 months. At entry, MHE was diagnosed
      when the Psychometric Hepatic Encephalopathy Score (PHES) was <= -4. Data were
      analyzed by logistic regression for the factors associated to MHE and by time
      related models for overt HE development and survival . RESULTS: at inclusion, 131
      out of 310 cirrhotic patients (42%) were affected by MHE. One hundred and twenty
      five patients (40%) were using PPIs. The variables independently associated to
      the presence of MHE were: PPIs use, previous overt HE, low albumin, low sodium
      and age. During follow-up, the development of overt HE was higher (64% vs 25%;
      p<0.001) and overall survival lower (41% vs 81%; p<0.001) in PPIs users than in
      non-users. Variables independently associated to the development of overt HE
      were: PPIs, history of overt HE, low albumin, MHE and age while variables
      independently associated to mortality were: PPIs, development of overt HE, MELD
      score, age, low sodium and age. CONCLUSION: the study identifies a potentially
      removable factor associated to the presence of minimal HE and related to the
      development of overt HE and survival in patients with liver cirrhosis. This
      article is protected by copyright. All rights reserved.

PMID- 30289993
TI  - Custom edge-element FEM solver and its application to eddy-current simulation of
      realistic 2M-element human brain phantom.
AB  - Extensive research papers of three-dimensional computational techniques are
      widely used for the investigation of human brain pathophysiology. Eddy current
      analyzing could provide an indication of conductivity change within a biological
      body. A significant obstacle to current trend analyses is the development of a
      numerically stable and efficiency-finite element scheme that performs well at low
      frequency and does not require a large number of degrees of freedom. Here, a
      custom finite element method (FEM) solver based on edge elements is proposed
      using the weakly coupled theory, which separates the solution into two steps.
      First, the background field (the magnetic vector potential on each edge) is
      calculated and stored. Then, the electric scalar potential on each node is
      obtained by FEM based on Galerkin formulations. Consequently, the electric field
      and eddy current distribution in the object can be obtained. This solver is more
      efficient than typical commercial solvers since it reduces the vector eddy
      current equation to a scalar one, and reduces the meshing domain to just the eddy
      current region. It can therefore tackle complex eddy current calculations for
      models with much larger numbers of elements, such as those encountered in eddy
      current computation in biological tissues. An example is presented with a
      realistic human brain mesh of 2 million elements. In addition, with this solver,
      the equivalent magnetic field induced from the excitation coil is applied, and
      therefore there is no need to mesh the excitation coil. In combination, these
      significantly increase the efficiency of the solver. Bioelectromagnetics. 39:604
      616, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30289995
TI  - Suboptimal Clinical Response Rates with Newer Antibiotics Among Patients with
      Moderate Renal Impairment: Review of the Literature and Potential Pharmacokinetic
      and Pharmacodynamic Considerations for Observed Findings.
AB  - A number of antibacterial agents have emerged into the U.S. market in the last 2
      decades to address growing concerns of antimicrobial resistance. These agents
      have demonstrated noninferiority to comparators for treatment of a range of
      complicated infections in their respective clinical trials. However, with select
      agents, a trend of reduced therapeutic efficacy was observed among study patients
      with baseline renal impairment. This phenomenon was seen in phase III studies
      involving ceftazidime-avibactam, ceftolozane-tazobactam, daptomycin, and
      telavancin. Although these were largely post hoc findings among small
      subpopulations, this observation is still concerning, given that renal impairment
      is a common occurrence among patients in real-world care settings. Cautions for
      use in this population are featured in the prescribing information of all four
      agents. Although well-defined reasons for these findings across trials are
      diverse or unknown, several potential pharmacokinetic and pharmacodynamic
      explanations for these discordant response rates exist. In this review, we
      summarize the phase III studies that observed lower response rates with
      ceftazidime-avibactam, ceftolozane-tazobactam, daptomycin, and telavancin
      relative to their comparators among patients with moderate renal impairment,
      discuss potential explanations for the observed findings, provide considerations
      for future antibiotic development, and offer strategies for optimizing antibiotic
      dosage selection among patients with moderate renal impairment in clinical
      settings. Although all of these agents are discussed, ceftazidime-avibactam is
      used as a motivating example to demonstrate the implications of inappropriate
      dosage selection.

PMID- 30289994
TI  - N-Acetylcysteine potentiates the haemodynamic-improving effect of sildenafil in a
      rabbit model of acute pulmonary thromboembolism via the p38 MAPK pathway.
AB  - The current study aimed to investigate the effects of sildenafil and N
      acetylcysteine (NAC) on the haemodynamics in a rabbit model of acute pulmonary
      thromboembolism (APT). We developed an APT model using healthy male China big-ear
      rabbits (2.7 +/- 0.4 kg). The rabbits were divided into five groups subjected to
      various interventions. We recorded the haemodynamic parameters and assessed the
      oxidative stress and lipid peroxidation response in the groups. Additionally, we
      detected apoptosis-associated molecules, FoxO1, Bad and Bcl-2, in the lung
      tissue. Gelatine zymography was used to detect matrix metalloproteinase (MMP)
      activity in bronchoalveolar lavage (BLA). Pulmonary artery endothelial cells were
      isolated, and their apoptosis rates and MMP activity were assayed. N
      acetylcysteine potentiated the haemodynamic-improving effect of sildenafil and
      significantly inhibited the oxidative stress response. N-acetylcysteine combined
      with sildenafil decreased MMP-2 and MMP-9 activity and NO consumption and
      inhibited apoptosis of pulmonary arterial endothelial cells. Moreover, NAC
      combined with sildenafil inhibited the expression of MCP-1 and p-p38 MAPK. Thus,
      NAC potentiates the haemodynamic-improving effect of sildenafil in a rabbit model
      of acute pulmonary thromboembolism via the MCP-1 and p38 MAPK signalling pathway.
      This study may provide a promising treatment method for APT.

PMID- 30289996
TI  - The antidepressant drug, sertraline, hinders bone healing and osseointegration in
      rats' tibiae.
AB  - AIM: Selective serotonin reuptake inhibitors (SSRIs) are one of the most common
      antidepressant drugs. SSRI use is associated with increased risk of bone fracture
      and titanium implant failure. The aim of this in vivo study was to investigate
      the effect of SSRIs on osseointegration and bone healing. MATERIALS AND METHODS:
      On a total of 24 Sprague-Dawley rats, a custom-made titanium implant was placed
      in the left tibia, while a unicortical defect was created in the right tibia.
      Rats were assigned randomly into two groups and received a daily dose of either
      sertraline (5 mg/kg) or saline. After two weeks, they were euthanized and bone
      healing and osseointegration were assessed by micro-CT and histology. RESULTS:
      Bone formation in bone defects was significantly lower (p < 0.05) in sertraline
      treated rats (BV/TV = 20.67 +/- 11.98%) compared to the controls (BV/TV = 37.87
      +/- 9.56%). Furthermore, the percentage of osseointegration was significantly
      lower (p < 0.05) in sertraline-treated rats (34.40 +/- 7.17%) compared to the
      controls (54.37 +/- 8.58%). CONCLUSION: Sertraline hinders bone healing and
      implant osseointegration.

PMID- 30289997
TI  - Recent developments and highlights in biomarkers in allergic diseases and asthma.
AB  - The potential of precision medicine in allergy and asthma has only started to be
      explored. A significant clarification in the pathophysiology of rhinitis, chronic
      rhinosinusitis, asthma, food allergy and drug hypersensitivity was made in the
      last decade. This improved understanding led to a better classification of the
      distinct phenotypes and to the discovery of new drugs such as biologicals,
      targeting phenotype-specific mechanisms. Nevertheless, many conditions remain
      poorly understood such as non-eosinophilic airway diseases or non-IgE-mediated
      food allergy. Moreover, there is a need to predict the response to specific
      therapies and the outcome of drug and food provocations. The identification of
      patients at risk of progression towards severity is also an unmet need in order
      to establish adequate preventive or therapeutic measures. The implementation of
      precision medicine in the clinical practice requires the identification of
      phenotype-specific markers measurable in biological matrices. To become useful,
      these biomarkers need to be quantifiable by reliable systems, and in samples
      obtained in an easy, rapid and cost-efficient way. In the last years, significant
      research resources have been put in the identification of valid biomarkers for
      asthma and allergic diseases. This review summarizes these recent advances with
      focus on the biomarkers with higher clinical applicability.

PMID- 30289998
TI  - Association between periodontitis and risk of Alzheimer's disease, mild cognitive
      impairment and subjective cognitive decline: A case-control study.
AB  - AIMS: To test the hypothesis that periodontal disease contributes to increased
      risk of mild cognitive impairment (MCI), subjective cognitive decline (SCD) and
      Alzheimer's disease (AD). MATERIALS AND METHODS: This case-control study was
      conducted over a 3-year period in the municipality of Huddinge, Sweden. In total,
      154 cases were consecutively enrolled from the Karolinska Memory Clinic at the
      Karolinska University Hospital and allotted to three diagnostic groups: AD, MCI
      and SCD, collectively referred to as "cases." Seventy-six cognitively healthy age
      and gender-matched controls were randomly sampled through the Swedish population
      register. All cases and controls underwent clinical and radiographic oral
      examinations. Statistical analysis was based on logistic regression models
      adjusted for potential confounders. RESULTS: Poor oral health and marginal
      alveolar bone loss were more prevalent among cases than among controls. The cases
      group was associated with generalized marginal alveolar bone loss (odds ratio
      [OR] = 5.81; 95% confidence interval [CI] = 1.14-29.68), increased number of deep
      periodontal pockets (OR = 8.43; CI 4.00-17.76) and dental caries (OR = 3.36; CI
      1.20-9.43). CONCLUSION: The results suggest that marginal periodontitis is
      associated with early cognitive impairment and AD. However, the study design does
      not preclude noncausal explanations.

PMID- 30289999
TI  - Boron: the essential element for vascular plants that never was.
AB  - Although a requirement for boron is a well-established feature of vascular
      plants, its designation, for almost a century, as essential is challenged and,
      instead, the proposal is made that it has never been so as conventionally
      defined. This is because an alternative interpretation of published evidence
      negates its compliance with one of the criteria for essentiality, that its
      effects are direct. The alternative, here postulated, is that boron is, and
      always has been, potentially toxic, a feature which, for normal growth,
      development and reproduction, needed to be nullified. This was enabled by
      exploitation of boron's ability to be chemically bound to compounds with cis
      hydroxyl groups. Although particular cell wall carbohydrate polymers,
      glycoproteins and membrane glycolipids are among candidates for this role, it is
      here proposed that soluble phenolic metabolites of, or related to, the components
      of the pathway of lignin biosynthesis, themselves potentially toxic, are
      primarily used by vascular plants. When metabolic circumstances allow these
      phenolics to accumulate endogenously in the cytoplasm, their own inherent
      toxicity is also alleviated, partially at least, by formation of complexes with
      boron. This chemical reciprocity, enhanced by physical sequestration of the
      complexes in vacuoles and/or apoplast, thus achieves, in a flexible but indirect
      manner, a minimization of the inherent toxicities of both boron and relevant
      phenolics. In these ways, the multifarious outcomes of impairments, natural or
      experimental, to this interplay are responsible for the lack of consensus to
      explain the diverse effects observed in the many searches for boron's primary
      metabolic role, here considered to be nonexistent. In particular, since a toxic
      element cannot have 'deficiency symptoms', those previously so-called are
      postulated to be largely due to the expressed toxicity of phenylpropanoids. A
      principal requirement for the otherwise toxic boron is to nullify, by means of
      its indirect chemical and physical sequestration, such expression. In these ways,
      it is therefore neither an essential nor a beneficial element as currently
      strictly defined.

PMID- 30290000
TI  - Omadacycline Enters the Ring: A New Antimicrobial Contender.
AB  - Omadacycline is a novel aminomethylcycline approved for the treatment of
      community-acquired bacterial pneumonia and acute bacterial skin and skin
      structure infections. This article reviews existing data pertaining to the
      biochemistry, mechanism of action, pharmacokinetics/pharmacodynamics, in vitro
      activity, and current progress with omadacycline in clinical trials. Omadacycline
      inhibits protein synthesis by binding to the 30S subunit of the bacterial
      ribosome at the tetracycline-binding site with an affinity similar to
      glycylcyclines. It is able to bypass older tetracycline resistance mechanisms and
      demonstrates activity against bacterial strains that are tetracycline resistant.
      In addition, omadacycline displays broad-spectrum activity against gram-positive
      organisms (including methicillin-resistant Staphylococcus aureus and vancomycin
      resistant enterococci), gram-negative organisms, atypical organisms, and
      anaerobes. It has been evaluated against infections in adults both intravenously
      and orally. Dosage adjustments are not required for patients with renal
      impairment. Omadacycline displays a comparable efficacy and safety profile to
      standard-of-care agents, with the most common side effects observed being
      gastrointestinal. Currently available data for omadacycline suggest that this is
      a promising agent added to our antimicrobial armamentarium.

PMID- 30290001
TI  - Unfolding the pleiotropic facades of rosuvastatin in therapeutic intervention of
      myriads of neurodegenerative disorders.
AB  - Rosuvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase
      inhibitor, and one of the most popular antihyperlipidemic medications has been
      found to possess pharmacodynamic activities much different from its usual
      indication. Recent research studies have revealed the efficacy of rosuvastatin in
      attenuating neuroinflammation, reducing the progression of Alzheimer's disease,
      providing protection against cerebral ischemia and spinal cord injury as well as
      ameliorating epilepsy. Mechanisms behind the neuroprotective potential of
      rosuvastatin can be attributed to its pleiotropic effects, independent of its
      ability to inhibit HMG-CoA reductase. These processes include modulation of
      several cellular pathways, isoprenylation, effects on oxidative stress,
      nitrosative levels, inflammation, and immune response. With this review, we aim
      to assimilate and summarize recent findings on the pharmacological actions of
      rosuvastatin in attenuating neurological disorders in order to give way for
      future research in this space. This article is protected by copyright. All rights
      reserved.

PMID- 30290002
TI  - Graphical representations and summary indicators to assess the performance of
      risk predictors.
AB  - The availability of novel biomarkers in several branches of medicine opens room
      for refining prognosis by adding factors on top of those having an established
      role. It is accepted that the impact of novel factors should not rely solely on
      regression coefficients and their significance but also on predictive power
      measures, such as Brier score and ROC-based quantities. However, novel factors
      that are promising at the exploratory stage often result in disappointingly low
      impact in the predictive power. This motivated the proposal of the net
      reclassification improvement and the integrated discrimination improvement, as
      direct measures of predictive power gain due to additional factors based on the
      concept of reclassification tables. These measures became extremely popular in
      cardiovascular disease and cancer applications, given the apparently easy
      interpretation. However, recent contributions in the biostatistical literature
      enlightened the tendency to indicate as advantageous models obtained by adding
      unrelated factors. These measures should not be used in practice. A further
      measure proposed a decade ago, the net benefit, is becoming a standard in
      assessing the consequences in terms of costs and benefits when using a risk
      predictor in practice for classification. This work reviews the conceptual
      formulations and interpretations of the available graphical methods and summary
      measures for evaluating risk predictor models. The aim is to provide guidance in
      the evaluation process that from the model development brings the risk predictor
      to be used in clinical practice for binary decision rules.

PMID- 30290003
TI  - Tyrosine kinase inhibitor interruptions, discontinuations and switching in
      patients with chronic-phase chronic myeloid leukemia in routine clinical
      practice: SIMPLICITY.
AB  - SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase
      inhibitor (TKI) use and management patterns in patients with chronic phase
      chronic myeloid leukemia in the US and Europe in routine clinical practice.
      Herein we describe interruptions, discontinuations and switching of TKI therapy
      during the initial 2 years of treatment among 1121 patients prospectively
      enrolled between October 1, 2010 and March 7, 2017. Patient characteristics were
      broadly similar between the imatinib (n = 370), dasatinib (n = 376), and
      nilotinib (n = 375) cohorts. Treatment interruptions occurred in 16.4% (year 1)
      and 4.0% (year 2) of patients, mainly attributed to hematologic intolerances.
      Treatment discontinuations occurred in 21.8% (year 1) and 10.2% (year 2) of
      patients, with the highest rate within the first 3 months for intolerance.
      Switching of TKI was seen in 17.8% (year 1) and 9.5% (year 2) of patients.
      Significant associations were found between TKI switching and female gender (year
      1), age >=65 years at diagnosis (year 2) and treatment with imatinib (year 2).
      Intolerance was the most common reason given for patients discontinuing and for
      switching TKI therapy; however resistance was also cited. Lack of response
      monitoring in routine clinical practice may have resulted in lower identification
      of resistance in this dataset. Data from SIMPLICITY suggest that, in routine
      clinical practice, intolerance and resistance to TKIs influence decisions to
      change treatment. Changes in TKI therapy are frequent, with nearly a third of
      patients discontinuing their first-line TKI.

PMID- 30290004
TI  - Point-of-care screening for sickle cell disease in low-resource settings: A multi
      center evaluation of HemoTypeSC, a novel rapid test.
AB  - Sickle cell disease (SCD) is a common, life-threatening genetic disorder that is
      best managed when diagnosed early by newborn screening. However, SCD is most
      prevalent in low-resource regions of the world where newborn screening is rare
      and diagnosis at the point-of-care is challenging. In many such regions, the
      majority of affected children die, undiagnosed, before the age of 5 years. A
      rapid and affordable point-of-care test for SCD is needed. The diagnostic
      accuracy of HemoTypeSC, a point-of-care immunoassay, for SCD was evaluated in
      individuals who had SCD, hemoglobin C disease, the related carrier (trait)
      states, or a normal hemoglobin phenotype. Children and adults participated in low
      , medium- and high-resource environments (Ghana [n = 383], Martinique [n = 46],
      and USA [n = 158]). Paired blood specimens were obtained for HemoTypeSC and a
      reference diagnostic assay. HemoTypeSC testing was performed at the site of blood
      collection, and the reference test was performed in a laboratory at each site. In
      587 participants, across all study sites, HemoTypeSC had an overall sensitivity
      of 99.5% and specificity of 99.9% across all hemoglobin phenotypes. The test had
      100% sensitivity and specificity for sickle cell anemia. Sensitivity and
      specificity for detection of normal and trait states were >99%. HemoTypeSC is an
      inexpensive (<$2 per test), accurate, and rapid point-of-care test that can be
      used in resource-limited regions with a high prevalence of SCD to provide timely
      diagnosis and support newborn screening programs.

PMID- 30290005
TI  - The journey of metformin from glycaemic control to mTOR inhibition and the
      suppression of tumour growth.
AB  - Our knowledge of the effect of metformin on human health is increasing. In
      addition to its ability to improve the control of hyperglycaemia, metformin has
      been shown to reduce the burden o,f ageing via effects on damaged DNA and the
      process of apoptosis. Studies have shown that metformin may reduce the risk of
      cardiovascular disease through influences on body weight, blood pressure,
      cholesterol levels and the progression of atherosclerosis. Studies also suggest
      that metformin may be beneficial for neuro-psychiatric disorders, cognitive
      impairment and in reducing the risk of dementia, erectile dysfunction and
      Duchenne muscular dystrophy. In vivo and in vitro studies have shown that
      metformin has anti-cancer properties, and population studies have suggested that
      metformin may reduce the risk of cancer or improve cancer prognosis. It is
      thought that it exerts its anti-cancer effect through the inhibition of the
      mammalian target of rapamycin (mTOR) signalling pathway. Because of its effect on
      the mTOR pathway, there may be a role for metformin in slowing or reversing
      growth of life-threatening hamartomas in tuberous sclerosis complex.

PMID- 30290006
TI  - Protective role of skeletal muscle mass against progression from metabolically
      healthy to unhealthy phenotype.
AB  - OBJECTIVE: Metabolically healthy individuals are known to be resistant to
      cardiovascular disease development. However, a considerable fraction of those
      individuals shows deteriorated metabolic health over time. Although skeletal
      muscle is the primary insulin-responsive target organ, a longitudinal
      investigation of the skeletal muscle mass in relation to the development of
      metabolically unhealthy phenotype has not been performed. We aimed to evaluate
      whether greater skeletal muscle mass is an independent protective factor for the
      development of metabolically unhealthy phenotype. DESIGN, PARTICIPANTS AND
      MEASUREMENTS: We conducted a retrospective cohort study with 9033 metabolically
      healthy volunteers who underwent routine health examinations in 2012 and a follow
      up examination in 2016. Obesity was defined as Asian-Pacific body mass index
      criterion >=25 kg/m2 . Subjects with fewer than two risk factors (elevated blood
      pressure, triglyceride, glucose, high-sensitivity C-reactive protein, insulin
      resistance and decreased high-density lipoprotein cholesterol levels) were
      characterized as metabolically healthy using Wildman criteria. RESULTS: At the 4
      year follow-up, approximately one-fourth of the nonobese participants and half of
      the participants with obesity showed metabolic deterioration. In nonobese men and
      women, higher appendicular skeletal muscle mass (ASM)/weight at baseline was
      significantly associated with decreased risk of metabolic deterioration. Compared
      to the lowest quartile of ASM/weight, the adjusted odds ratios (95% confidence
      intervals) of the highest quartile were 0.68 (0.52-0.89) in nonobese men and 0.64
      (0.46-0.90) in nonobese women. However, this association was not observed in
      obese subjects. CONCLUSIONS: Greater skeletal muscle mass at baseline is
      significantly associated with maintenance of metabolically healthy status,
      especially in nonobese individuals.

PMID- 30290007
TI  - A 5-year prospective study on the clinical and aesthetic outcomes of alveolar
      ridge preservation and connective tissue graft at the buccal aspect of single
      implants.
AB  - AIM: To evaluate the 5-year aesthetic outcome of single implants following
      alveolar ridge preservation (ARP) and connective tissue graft (CTG) at the buccal
      aspect. MATERIALS AND METHODS: Thirty-seven periodontally healthy non-smoking
      patients received flapless tooth extraction, ARP with a deproteinized bovine bone
      mineral with 10% collagen (DBBMC), implant placement (4-6 months later), a
      provisional screw-retained crown and CTG at the buccal mucosa (3 months later)
      and a permanent crown (3 months later). The aesthetic results were the primary
      outcome and the clinical results the secondary outcome of the study. Both
      outcomes were compared to those after 1 year. Mucosal thickness (MT) was
      registered using a non-invasive ultrasonic device. RESULTS: Thirty-two patients
      attended the 5-year re-assessment, and all implants survived. Mean marginal bone
      loss was 0.53 mm at 1 year and 0.47 mm at 5 years (p = 0.439). Mesial Papilla
      showed a further re-growth between 1 and 5 years (p = 0.043). Mid-facial
      recession amounted to 0.05 mm and 0.12 mm at 1 and 5 years, respectively (p =
      0.161). The Pink Esthetic Score was 11.00 and 11.17 at 1 and 5 years,
      respectively (p = 0.596). MT gain amounted to 0.97 mm (relative stability: 90.5%)
      and 0.91 mm (relative stability: 85%) at 1 and 5 years, respectively (p = 0.249).
      CONCLUSION: ARP and CTG resulted in favourable clinical and aesthetic outcomes.
      CTG substantially increased MT with acceptable stability over a 5-year period.

PMID- 30290008
TI  - Donepezil-melatonin hybrids as butyrylcholinesterase inhibitors: Improving
      binding affinity through varying mode of linking fragments.
AB  - Hybrid inhibitors of acetyl- and butyrylcholinesterase are compounds that combine
      structural motifs of two different classical inhibitors, leading to a dual
      binding ligand. A rapidly growing collection of those compounds involves a wide
      diversity of structural motifs, but the way of linking two active fragments and
      its impact on the affinity toward cholinesterases usually remains beyond the
      extent of investigation. We present hereby a detailed analysis of this aspect
      using melatonin-donepezil hybrids. A new series of compounds, in which two
      fragments are connected using a carbamate linker, exhibits excellent activity and
      selectivity toward butyrylcholinesterase.

PMID- 30290009
TI  - Neighbor balance and evenness of distribution of treatment replications in row
      column designs.
AB  - Row-column designs allow error control in field experiments by blocking in two
      dimensions. While this strategy can capture spatial heterogeneity aligned with
      blocks and account for effects due to the farming operations along rows and
      columns, it suffers from the occasional clustered occurrence of several
      replications of the same treatment. This property of classical row-column designs
      has hampered their more widespread use in practice. A further issue of practical
      importance is the degree of neighbor balance of a design, that is, the frequency
      of adjacencies of pairs of treatments. This paper proposes two design strategies
      to simultaneously optimize the evenness of spatial distribution of treatment
      replication as well as neighbor balance. Three examples are given to illustrate
      the proposed methods and demonstrate that both approaches yield comparable and
      satisfactory results.

PMID- 30290010
TI  - Verticillium dahliae transcription factors Som1 and Vta3 control microsclerotia
      formation and sequential steps of plant root penetration and colonisation to
      induce disease.
AB  - Verticillium dahliae nuclear transcription factors Som1 and Vta3 can rescue
      adhesion in a FLO8-deficient Saccharomyces cerevisiae strain. Som1 and Vta3
      induce the expression of the yeast FLO1 and FLO11 genes encoding adhesins. Som1
      and Vta3 are sequentially required for root penetration and colonisation of the
      plant host by V. dahliae. The SOM1 and VTA3 genes were deleted and their
      functions in fungus-induced plant pathogenesis were studied using genetic, cell
      biology, proteomic and plant pathogenicity experiments. Som1 supports fungal
      adhesion and root penetration and is required earlier than Vta3 in the
      colonisation of plant root surfaces and tomato plant infection. Som1 controls
      septa positioning and the size of vacuoles, and subsequently hyphal development
      including aerial hyphae formation and normal hyphal branching. Som1 and Vta3
      control conidiation, microsclerotia formation, and antagonise in oxidative stress
      responses. The molecular function of Som1 is conserved between the plant pathogen
      V. dahliae and the opportunistic human pathogen Aspergillus fumigatus. Som1
      controls genes for initial steps of plant root penetration, adhesion, oxidative
      stress response and VTA3 expression to allow subsequent root colonisation. Both
      Som1 and Vta3 regulate developmental genetic networks required for conidiation,
      microsclerotia formation and pathogenicity of V. dahliae.

PMID- 30290011
TI  - Cis-trans controls and regulatory novelty accompanying allopolyploidization.
AB  - Allopolyploidy is a prevalent process in plants, having important physiological,
      ecological and evolutionary consequences. Transcriptomic responses to genomic
      merger and doubling have been demonstrated in many allopolyploid systems,
      encompassing a diversity of phenomena including homoeolog expression bias, genome
      dominance, expression-level dominance and revamping of co-expression networks.
      Notwithstanding the foregoing, there remains a need to develop a conceptual
      framework that will stimulate a deeper understanding of these diverse phenomena
      and their mechanistic interrelationships. Here we introduce considerations
      relevant to this framework with a focus on cis-trans interactions among
      duplicated genes and alleles in hybrids and allopolyploids. By extending classic
      allele-specific expression analysis to the allopolyploid level, we distinguish
      the distinct effects of progenitor regulatory interactions from the novel
      intergenomic interactions that arise from genome merger and allopolyploidization.
      This perspective informs experiments designed to reveal the molecular genetic
      basis of gene regulatory control, and will facilitate the disentangling of
      genetic from epigenetic and higher-order effects that impact gene expression.
      Finally, we suggest that the extended cis-trans model may help conceptually unify
      several presently disparate hallmarks of allopolyploid evolution, including
      genome-wide expression dominance and biased fractionation, and lead to a new
      level of understanding of phenotypic novelty accompanying polyploidy.

PMID- 30290012
TI  - Maternal L-carnitine supplementation ameliorates renal underdevelopment and
      epigenetic changes in male mice offspring due to maternal smoking.
AB  - OBJECTIVES: Epidemiological and animal studies showed that L-carnitine (LC)
      supplementation can ameliorate oxidative stress-induced tissues damage. We have
      previously shown that maternal cigarette smoke exposure (SE) can increase renal
      oxidative stress in newborn offspring with postnatal kidney underdevelopment and
      renal dysfunction in adulthood, which were normalised by LC administration in the
      SE dams during pregnancy. Exposure to an adverse intrauterine environment may
      lead to alteration in the epigenome, a mechanism by which adverse prenatal
      conditions increase the susceptibility to chronic disease later in life. The
      current study aimed to determine whether maternal SE induces epigenetic changes
      in the offspring's kidney are associated with renal underdevelopment, and the
      protective effect of maternal LC supplementation. METHOD: Female Balb/c mice (7
      weeks) were exposed to cigarette smoke (SE) or air (Sham) for 6 weeks prior to
      mating, during gestation and lactation. A subgroup of the SE dams received LC via
      drinking water (SE + LC, 1.5 mmol/L) throughout gestation and lactation. Male
      offspring were studied at postnatal day (P)1, P20, and 13 weeks. RESULTS:
      Maternal SE altered the expression of renal development markers glial cell line
      derived neurotrophic factor and fibroblast growth factor 2, which were associated
      with increased renal global DNA methylation and DNA methyltransferase 1 mRNA
      expression at birth. These disorders were reversed by maternal LC administration.
      CONCLUSION: The effect of maternal SE on renal underdevelopment involves global
      epigenetic alterations from birth, which can be prevented by maternal LC
      supplementation.

PMID- 30290013
TI  - Incidence of cytomegalovirus in cardiac transplant recipients receiving induction
      immunosuppression with antithymocyte globulin.
AB  - BACKGROUND: Cytomegalovirus (CMV) is a major cause of morbidity and mortality in
      cardiac transplant recipients. Use of induction immunosuppression in cardiac
      transplantation may have an impact on the incidence of CMV, but literature is
      limited. METHODS: Single-center, retrospective cohort study comparing the risk of
      CMV infection and disease in cardiac transplant patients receiving antithymocyte
      globulin (ATG) induction therapy to those receiving no antibody induction.
      RESULTS: A total of 75 patients were included in our analysis, 50 who received
      ATG induction and 25 who did not. CMV infection occurred in 10 (20%) and 5 (20%)
      patients in the ATG and No ATG groups, respectively (P > 0.99). CMV disease
      occurred in 10 (20%) and 4 (16%) patients in the ATG and No ATG groups,
      respectively (P = 0.763). The median time from transplant to CMV infection was
      200.0 [142.5, 364.5] days in the ATG group vs 221.0 [192.0, 299.0] days in the No
      ATG group (P = 0.723). The median time from end of CMV prophylaxis to CMV
      infection was 94.5 [66.5, 151.0] days in the ATG group vs 53.0 [41.0,149.5] days
      in the No ATG group (P = 0.202). Freedom from CMV infection was highest in the
      D+/R+ group and lowest in the D+/R- group. CONCLUSION: In cardiac transplant
      recipients, ATG induction was not associated with an increased incidence of CMV
      infection or disease in the setting of valganciclovir prophylaxis and an initial
      maintenance immunosuppression regimen of primarily steroids, mycophenolate
      mofetil, and tacrolimus.

PMID- 30290014
TI  - Leptin impairs the therapeutic effect of ionizing radiation in oral squamous cell
      carcinoma cells.
AB  - PURPOSE: Leptin, an important hormone controlling energy homeostasis, has been
      linked to the pathogenesis of oral squamous cell carcinoma (OSCC). Evidence
      indicates that head and neck cancer patients undergoing radiotherapy show
      decreased leptin levels after radiotherapy treatment. Thus, we investigated,
      through phenotypic and molecular analyses, whether leptin can compromise the
      therapeutic effect of ionizing radiation and neoplastic behavior of OSCC cells.
      METHODS: The human OSCC-derived cell lines SCC9 and SCC4 were treated with human
      recombinant leptin and exposed to 6 Gy of irradiation. We performed the in vitro
      assays of cell migration, death, proliferation, and colony-forming ability. The
      reactive oxygen species (ROS) levels and proteome analysis by mass spectrometry
      were also conducted. RESULTS: Leptin was able to increase cell proliferation,
      migration, and colony-forming ability, despite the suppressive effect induced by
      irradiation. Furthermore, the leptin promoted a significant reduction of ROS
      intracellular accumulation, and increased expression of the cancer-related
      proteins, as ACTC1, KRT6A, and EEF2 in irradiated OSCC cells. CONCLUSIONS: Our
      findings suggest that leptin impairs responsivity of OSCC cells to the ionizing
      radiation, reducing the suppressive effects of irradiation on the neoplastic
      phenotype, and increasing protein expression critical to carcinogenesis.

PMID- 30290015
TI  - Concurrent Infection of Batrachochytrium dendrobatidis and Ranavirus among Native
      Amphibians from Northeastern Oklahoma, USA.
AB  - Global amphibian decline continues to be a great concern despite our increased
      understanding of the causes behind the observed patterns of the decline, such as
      habitat modification and infectious diseases. Although there is a large body of
      literature on the topic of amphibian infectious diseases, pathogen prevalence and
      distribution among entire communities of species in many regions remain poorly
      understood. In addition to these geographic gaps in our understanding, past work
      has focused largely on individual pathogens, either Batrachochytrium
      dendrobatidis (Bd) or ranavirus (RV), rather than dual infection rates among host
      species. We sampled for prevalence and infection load of both pathogens in 514
      amphibians across 16 total sites in northeastern Oklahoma. Amphibians were caught
      by hand, net, or seine; they were swabbed to screen for Bd; and liver tissue
      samples were collected to screen for RV. Overall results of quantitative PCR
      assays showed that 7% of screened individuals were infected with RV only, 37%
      were infected with Bd only, and 9% were infected with both pathogens
      simultaneously. We also documented disease presence in several rare amphibian
      species that are currently being monitored as species of concern due to their
      small population sizes in Oklahoma. This study synthesizes a growing body of
      research regarding infectious diseases among amphibian communities in the central
      United States.

PMID- 30290016
TI  - The value of dermoscopy in diagnosing eyebrow loss in patients with alopecia
      areata and frontal fibrosing alopecia.
AB  - INTRODUCTION: Alopecia areata and frontal fibrosing alopecia are common causes of
      eyebrow loss (madarosis). OBJECTIVE: Assessment of trichoscopic markers of
      eyebrow loss in alopecia areata and frontal fibrosing alopecia. MATERIALS AND
      METHODS: The analysis included 50 patients with scalp alopecia areata with
      madarosis, 50 patients with scalp frontal fibrosing alopecia with madarosis and
      50 healthy controls. In every case, trichoscopy of the eyebrow area was
      performed. RESULTS: Empty follicular and eccrine duct openings were observed in
      all patients and presented predominantly as yellow dots. Exclamation mark hairs
      were only detected in patients with alopecia areata (30%). Tapered hairs, broken
      hair, black dots and Pohl-Pinkus constrictions were observed in 14%, 36%, 26% and
      4% of patients with alopecia areata, respectively, 4%, 16%, 2% and 0% of patients
      with frontal fibrosing alopecia, respectively, and they were not present in
      healthy controls. Dystrophic hairs and whitish areas were observed only in
      patients with frontal fibrosing alopecia (28% and 32%, respectively). Eyebrow
      regrowth in distinct directions was present in 32% of patients with frontal
      fibrosing alopecia, 8% of patients with alopecia areata and 4% of healthy
      controls. Diffuse erythema was detected in 60% of patients with alopecia areata
      and frontal fibrosing alopecia and 56% of healthy controls. Vellus hairs and
      upright regrowing hairs were observed in patients with alopecia areata (62% and
      58%, respectively), frontal fibrosing alopecia (60% and 84%, respectively) and
      healthy controls (100% and 100%, respectively). CONCLUSION: Trichoscopy of the
      eyebrow area is useful in diagnosing patients with isolated eyebrow loss. The
      most characteristic trichoscopic features of eyebrow loss in alopecia areata
      include exclamation mark hairs, tapered hairs, broken hairs and black dots.
      Frontal fibrosing alopecia of the eyebrows is characterized by the presence of
      dystrophic hairs, white areas and eyebrow regrowth in distinct directions.

PMID- 30290017
TI  - Role of synovium-derived fibrous cartilage in temporomandibular joint synovial
      chondromatosis.
AB  - BACKGROUND: Synovial chondromatosis (SC) of temporomandibular joint (TMJ)
      occupies 3% SC cases. In other joints like hip and knee which were composed
      hyaline cartilage (HC), loose bodies (LBs) were reported to be a HC feature.
      However, condyle surface and disc in TMJ are fibrous cartilage (FC). Therefore,
      we proposed a different pathogenesis of TMJSC. METHODS: LBs and synovium were
      collected from seven TMJSC patients, and histological and immunohistological
      examinations were performed. RESULTS: Three ways of HC formation were discovered:
      regular-shaped cartilaginous nodules (CNs) in sublining layer (SL) of
      vascularized synovium, regional chondrification of SL, and finger-like tissue
      with a tail attaching to synovium. Detached LBs could fuse and were only
      positively stained by aggrecan. Without synovium attachment to LBs, fused LBs
      remained a hyaline extracellular matrix (ECM). However, after synovium
      attachment, transformation from HC to FC occurred. Two types of FC were observed.
      First type FC was featured by vertical-distributed type I collagen fibers
      imbedding few chondrocytes, suggesting mature phase with superior mechanical
      features. Second type FC was featured by medium-density chondrocytes with type I
      collagen and aggrecan-positive ECM, suggesting primary phase. The transformation
      process started in appearance of 2nd type FC deriving from synovium covering LB,
      and gradually replaced HC from periphery to center. CONCLUSIONS: Three ways of HC
      formation were closely related. Different with SC in other joints, hyaline ECM in
      LBs of TMJSC could be replaced by FC deriving from synovium, during which 2nd
      type FC first replaced HC and then transformed to 1st type FC.

PMID- 30290018
TI  - Brimonidine displays anti-inflammatory properties in the skin through the
      modulation of the vascular barrier function.
AB  - BACKGROUND: Rosacea is a chronic inflammatory skin disease. Characteristic
      vascular changes in rosacea skin include enlarged, dilated vessels of the upper
      dermis and blood flow increase. Brimonidine is approved for symptomatic relief of
      the erythema of rosacea. It acts by selectively binding to alpha2-adrenergic
      receptors present on smooth muscle in the peripheral vasculature, resulting in
      transient local vasoconstriction. OBJECTIVES: To provide further evidence of the
      anti-inflammatory potential of brimonidine across preclinical models of skin
      inflammation and its ability to decrease the neutrophil infiltration in human
      skin after ultraviolet light exposure. METHODS: The anti-inflammatory properties
      of brimonidine through modulation of the vascular barrier function were assessed
      using in vivo neurogenic vasodilation and acute inflammatory models and a well
      described in vitro transmigration assay. A clinical study assessed the neutrophil
      infiltration in human skin after exposure to UV in 37 healthy Caucasian male
      subjects. RESULTS: In vitro, brimonidine affects the transmigration of human
      neutrophils through the endothelial barrier by modulating adhesion molecules. In
      vivo, in the mouse, topical treatment with brimonidine, used at a
      vasoconstrictive dose, confirmed its anti-inflammatory properties and prevented
      leucocyte recruitment (rolling and adhesion) mediated by endothelial cells.
      Topical pretreatment with brimonidine tartrate 0.33% gel once a day for 4 days
      significantly prevented neutrophil infiltration by 53.9% in human skin after
      exposure to UV light. CONCLUSION: Results from in vitro, in vivo and from a
      clinical study indicate that brimonidine impacts acute inflammation of the skin
      by interfering with neurogenic activation and/or recruitment of neutrophils.

PMID- 30290019
TI  - Declining in liver stiffness cannot indicate fibrosis regression in patients with
      chronic hepatitis B: A 78-week prospective study.
AB  - BACKGROUND AND AIM: Little reliable data are available about the liver stiffness
      measurement (LSM) for fibrosis monitoring in chronic hepatitis B (CHB) patients
      on antiviral therapy. We aimed to assess the accuracy of LSM in fibrosis
      monitoring during 78-week antiviral therapy in CHB patients. METHODS: Five
      hundred fifty-six treatment-naive CHB patients with qualified LSM and liver
      biopsy at baseline were analyzed. Patients receiving entecavir-based therapy were
      prospectively followed to 78 weeks for second LSM and liver biopsy. Serologic
      detection, LSM, and liver biopsy were performed on the same day. Necro
      inflammatory activity was also evaluated. RESULTS: Areas under receiver operating
      characteristics curves of LSM at baseline and week 78 for significant fibrosis
      (>= F3), advanced fibrosis (>= F4), and liver cirrhosis (>= F5) was 0.84, 0.87,
      0.83 and 0.76, 0.85, 0.88, respectively. Patients with the same fibrosis stage
      but higher histology activity index score tend to have higher LSM at baseline.
      Liver stiffness decreased rapidly (3.8 [1.6-8.6] kPa) in parallel with baseline
      histology activity index scores from 11.3 (7.8-16.7) kPa at baseline to 6.4 (5.1
      8.8) kPa at week 78. Greater decline of LSM in patients with only inflammation
      improvement was observed as compared with those without inflammation improvement
      (5.2 [2.5-9.7] vs 1.8 [0.2-8.1] kPa, P = 0.013). Baseline Ishak fibrosis score
      was the only predictor of 78-week fibrosis improvement (odds ratio, 1.859; P =
      0.000). CONCLUSIONS: In CHB patients receiving 78-week antiviral treatment, LSM
      could diagnosis different liver fibrosis stages, decrease in absolute LSM value
      could reflect the remission of liver inflammation, and baseline Ishak fibrosis
      score was the only predictor for 78-week fibrosis reversion.

PMID- 30290020
TI  - Nilotinib induction of melanogenesis via reactive oxygen species-dependent JNK
      activation in B16F0 mouse melanoma cells.
AB  - Nilotinib (AMN), a second-generation tyrosine kinase inhibitor, induces apoptosis
      in various cancer cells, and our recent study showed that AMN effectively reduced
      the viability of human ovarian cancer cells via mitochondrion-dependent
      apoptosis. The effect of AMN in the melanogenesis of melanoma cells is still
      unclear. In the present study, we found that the addition of AMN but not imatinib
      (STI) significantly increased the darkness of B16F0 melanoma cells, and the
      absorptive value increased with the concentration of AMN. A decrease in the
      viability of B16F0 cells by AMN was detected in a concentration-dependent manner,
      accompanied by increased DNA ladders, hypodiploid cells and cleavage of the
      caspase-3 protein. An in vitro tyrosinase (TYR) activity assay showed that
      increased TYR activity by AMN was detected in a concentration-dependent manner;
      however, induction of TYR activity by STI at a concentration of 40 MUmol/L was
      observed. Increased intracellular peroxide by AMN was detected in B16F0 cells,
      and application of the antioxidant, N-acetylcysteine (NAC), significantly reduced
      AMN-induced peroxide production which also reduced the darkness of B16F0 cells.
      Additionally, AMN induced c-Jun N-terminal kinase (JNK) protein phosphorylation
      in B16F0 cells, which was inhibited by the addition of NAC. AMN-induced
      melanogenesis of B16F0 cells was significantly inhibited by the addition of NAC
      and the JNK inhibitor, SP600125 (SP). Data of Western blotting showed that
      increased protein levels of melanogenesis-related enzymes of tyrosinase-related
      protein-1 (TRP1), TRP2 and TYR were observed in AMN-treated B16F0 cells which
      were inhibited by the addition of NAC and SP. Evidence is provided supporting AMN
      effectively inducing the melanogenesis of B16F0 melanoma cells via reactive
      oxygen species-dependent JNK activation.

PMID- 30290021
TI  - Evidence-based clinical guidelines on analgesia and sedation in newborn infants
      undergoing assisted ventilation and endotracheal intubation.
AB  - AIM: This review informed pain control guidelines for clinicians performing
      mechanical ventilation, nasal continuous positive airway pressure and
      endotracheal intubation on term and preterm newborn infants. METHODS: We reviewed
      literature published between 1986 and June 2017 on analgesia and sedation during
      assisted ventilation and before endotracheal intubation in newborn infants
      admitted to neonatal intensive care units. The subsequent guidelines were
      developed using the Grading of Recommendations Assessment, Development and
      Evaluation approach. RESULTS: Our review produced five strong standard of care
      recommendations. One, reduce neonatal stress and use nonpharmacological analgesia
      during invasive ventilation. Two, favour intermittent boluses of opioids,
      administered after pain scores and before invasive procedures, during short
      expected periods of mechanical ventilation, mainly in preterm infants affected by
      respiratory distress syndrome. Three, do not use morphine infusion in preterm
      infants under 27 gestational weeks. Four, always use algometric scores to titrate
      analgesic drugs doses. Five, use premedication before endotracheal intubation for
      a more rapid, less painful, less traumatic and safer manoeuvre. We also developed
      30 conditional recommendations on therapeutic options. CONCLUSION: Our review
      produced 35 recommendations on standard care and therapeutic options relating to
      the analgesia and sedation of newborn infants during ventilation and before
      endotracheal intubation.

PMID- 30290022
TI  - Toxicity of iron oxide nanoparticles: Size and coating effects.
AB  - Toxicological research of novel nanomaterials is a major developmental step of
      their clinical approval. Since iron oxide magnetic nanoparticles have a great
      potential in cancer treatment and diagnostics, the investigation of their toxic
      properties is very topical. In this paper we synthesized bovine serum albumin
      coated iron oxide nanoparticles with different sizes and their polyethylene
      glycol derivative. To prove high biocompatibility of obtained nanoparticles the
      number of in vitro toxicological tests on human fibroblasts and U251 glioblastoma
      cells was performed. It was shown that albumin nanoparticles' coating provides a
      stable and biocompatible shell and prevents cytotoxicity of magnetite core. On
      long exposure times (48 hours), cytotoxicity of iron oxide nanoparticles takes
      place due to free radical production, but this toxic effect may be neutralized by
      using polyethylene glycol modification.

PMID- 30290023
TI  - Low irradiance compared with conventional photodynamic therapy in the treatment
      of actinic keratoses.
AB  - BACKGROUND: Photodynamic therapy (PDT) is an effective therapy treating
      photodamaged areas with multiple actinic keratoses (AK). Still pain during
      therapy is one of the most challenging obstacles for patients. This retrospective
      study compares pain and efficacy intra-individual in patients using conventional
      PDT (c-PDT) compared to a low irradiance PDT protocol (li-PDT) with a reduced
      irradiance to 25% of c-PDT. METHODS: Thirty-one patients were enrolled into this
      retrospective analysis treated with li-PDT and c-PDT on comparable fields of
      actinic damage on the forehead or the cheek. Pain was scored by the patients
      using a VAS. Moreover, number and time to therapy interruptions were documented.
      For effectiveness number and grade of AK were counted before and 4 weeks after
      PDT. RESULTS: Maintaining a total light dose of 37 J/cm2 , a decrease in
      irradiation in li-PDT patients resulted in significant less pain (VAS score 2.8
      vs 7.6) and fewer therapy interruptions compared to treatment with c- PDT (P <
      0.0005). No significant difference in treatment outcome was found (P = 0.068).
      CONCLUSION: Our data shows that li-PDT can reduce pain with at least comparable
      clinical outcome compared to c-PDT. Therefore, it is an effective and well
      tolerated treatment for patients with multiple AK.

PMID- 30290024
TI  - From the Editors.

PMID- 30290025
TI  - Cardiac xenografts show reduced survival in the absence of transgenic human
      thrombomodulin expression in donor pigs.
AB  - A combination of genetic manipulations of donor organs and target-specific
      immunosuppression is instrumental in achieving long-term cardiac xenograft
      survival. Recently, results from our preclinical pig-to-baboon heterotopic
      cardiac xenotransplantation model suggest that a three-pronged approach is
      successful in extending xenograft survival: (a) alpha-1,3-galactosyl transferase
      (Gal) gene knockout in donor pigs (GTKO) to prevent Gal-specific antibody
      mediated rejection; (b) transgenic expression of human complement regulatory
      proteins (hCRP; hCD46) and human thromboregulatory protein thrombomodulin (hTBM)
      to avoid complement activation and coagulation dysregulation; and (c) effective
      induction and maintenance of immunomodulation, particularly through co
      stimulation blockade of CD40-CD40L pathways with anti-CD40 (2C10R4) monoclonal
      antibody (mAb). Using this combination of manipulations, we reported significant
      improvement in cardiac xenograft survival. In this study, we are reporting the
      survival of cardiac xenotransplantation recipients (n = 3) receiving xenografts
      from pigs without the expression of hTBM (GTKO.CD46). We observed that all grafts
      underwent rejection at an early time point (median 70 days) despite utilization
      of our previously reported successful immunosuppression regimen and effective
      control of non-Gal antibody response. These results support our hypothesis that
      transgenic expression of human thrombomodulin in donor pigs confers an
      independent protective effect for xenograft survival in the setting of a co
      stimulation blockade-based immunomodulatory regimen.

PMID- 30290027
TI  - Direct recanalization of pancreaticogastrostomy obstruction with a forward
      viewing echoendoscope.

PMID- 30290026
TI  - Synthesis, Structure and Nickel Carbonyl Complexes of Dialkylterphenyl
      Phosphines.
AB  - The experimental and computational characterization of a series of
      dialkylterphenyl phosphines, PR2 Ar' is described. The new P-donors comprise five
      compounds of general formula PR2 Ar Dtbp2 (R=Me, Et, iPr, c-C5 H9 and c-C6 H11 );
      Ar Dtbp2 = 2,6-C6 H3 -(3,5-C6 H3 -(CMe3 )2 )2 ), and another five PR2 Ar'
      phosphines containing the bulky alkyl groups iPr, c-C5 H9 or c-C6 H11 , in
      combination with Ar'=Ar Xyl2 , Ar Xyl'2 , or Ar Ph2 (L1-L10). Steric and
      electronic parameters have been determined computationally and from IR and X-ray
      data obtained for the phosphines and for some derivatives, including tricarbonyl
      and dicarbonyl nickel complexes, Ni(CO)3 (PR2 Ar') and Ni(CO)2 (PR2 Ar'). In the
      solid state, the free phosphines PR2 Ar' adopt one of the three possible
      structures formally related by rotation around the Cipso -P bond. Details on
      their relative energies and on the influence of the free phosphine structure on
      its coordination chemistry towards Ni(CO)n (n = 2, 3) fragments has been obtained
      by experimental and computational methods.

PMID- 30290028
TI  - INSM1 expression in pancreatic neuroendocrine tumors in endoscopic ultrasound
      guided fine needle aspiration cytology: an analysis of 14 patients.
AB  - BACKGROUND: Insulinoma-associated protein 1 (INSM1) has been reported to be a
      useful marker for diagnosing pancreatic neuroendocrine tumors (PNETs). However,
      INSM1 expression in endoscopic ultrasound-fine needle aspiration cytology (EUS
      FNAC) has not been examined. We evaluated INSM1 expression in the cytology of
      cases diagnosed with PNETs. METHODS: We immunocytochemically stained INSM1 and Ki
      67 in 14 PNET cases, and according to the 2017 World Health Organization
      criteria, 7 PNET Grade 1 (G1) cases, 4 Grade 2 (G2) cases, and 3 Grade 3
      (G3)/neuroendocrine carcinoma (NEC) cases were identified. As a control for INSM1
      and Ki-67 expression, we used cytological specimens from 15 cases of pancreatic
      ductal adenocarcinoma (PDAC). RESULTS: In PNET cases, INSM1-expressing tumor
      cells were identified in all cytological specimens of PNET. The median INSM1
      expression rate in G1 cases was 49.8% (mean+/-SD: 55.1+/-12.5%, min: 39.3%, max:
      74.1%), and in G2 and G3/NEC cases was 81.1% (mean+/-SD: 77.6+/-18.6%, min:
      50.3%, max: 100%). However, there was no correlation between INSM1 and Ki-67
      expression (r= -0.15).The median expression rate in PNET cases was 64.3%, which
      was significantly higher than that in PDAC cases (p<0.0001). CONCLUSION: INSM1
      immunocytochemistry of cytological specimens obtained from EUS-FNAC can
      accurately diagnose PNETs; therefore, INSM1 could be an important diagnostic tool
      in assessing therapeutic strategies, including molecular-targeted therapy. This
      article is protected by copyright. All rights reserved.

PMID- 30290029
TI  - Neural basis of goal-driven changes in knowledge activation.
AB  - Depending on a person's goals, different aspects of stored knowledge are
      accessed. Decades of behavioral work document the flexible use of knowledge, but
      little neuroimaging work speaks to these questions. We used representational
      similarity analysis to investigate whether the relationship between brain
      activity and semantic structure of statements varied in two tasks hypothesized to
      differ in the degree to which knowledge is accessed: judging truth (semantic
      task) and judging oldness (episodic task). During truth judgments, but not
      old/new recognition judgments, a left-lateralized network previously associated
      with semantic memory exhibited correlations with semantic structure. At a neural
      level, people activate knowledge representations in different ways when focused
      on different goals. The present results demonstrate the potential of multivariate
      approaches in characterizing knowledge storage and retrieval, as well as the ways
      that it shapes our understanding and long-term memory.

PMID- 30290030
TI  - Microvesicles Secreted by Nitric Oxide-Primed Mesenchymal Stromal Cells Boost the
      Engraftment Potential of Hematopoietic Stem Cells.
AB  - Patients with leukemia, lymphoma, severe aplastic anemia, etc. are frequently the
      targets of bone marrow transplantation, the success of which critically depends
      on efficient engraftment by transplanted hematopoietic cells (HSCs). Ex vivo
      manipulation of HSCs to improve their engraftment ability becomes necessary when
      the number or quality of donor HSCs is a limiting factor. Due to their
      hematopoiesis-supportive ability, bone marrow-derived mesenchymal stromal cells
      (MSCs) have been traditionally used as feeder layers for ex vivo expansion of
      HSCs. MSCs form a special HSC-niche in vivo, implying that signaling mechanisms
      operative in them would affect HSC fate. We have recently demonstrated that AKT
      signaling prevailing in the MSCs affect the HSC functionality. Here we show that
      MSCs primed with nitric oxide donor, Sodium nitroprusside (SNP), significantly
      boost the engraftment potential of the HSCs co-cultured with them via
      intercellular transfer of microvesicles (MVs) harboring mRNAs encoding HSC
      supportive genes. Our data suggest that these MVs could be used as HSC-priming
      agents to improve transplantation efficacy. Since both, nitric oxide donors and
      MSCs are already in clinical use; their application in clinical settings may be
      relatively straight forward. This approach could also be applied in regenerative
      medicine protocols. Stem Cells 2018.

PMID- 30290031
TI  - Rethinking the evolution of property and possession: A review and methodological
      proposition.
AB  - Property is a key feature of modern human society; however, identifying the
      origin of this multifaceted behavior poses a formidable challenge. Here, we
      explore the methodologies for researching the origin of property. We discuss how
      an interdisciplinary approach can shed light on how our human ancestors shifted
      behaviorally from possessing an object to having exclusive property control over
      it. Possession occurs when social group members only respect an individual's
      claim to have exclusive access to an object when the individual has physical
      control over the object. Property occurs when an individual can claim exclusive
      access to an object, without challenge, regardless of whether the object is in
      their physical control or not. Researchers across different disciplines have
      asked what, if anything, distinguishes human property behavior from the behavior
      of other animals? Further, when and how did this behavior evolve in our lineage?
      Due to the considerable methodological challenges posed by researching this
      topic, few studies have been able to directly address these questions. In this
      review, we explore the challenges involved in defining property and possession
      and suggest a two-step approach to interdisciplinary definitions. Next, we
      evaluate four core approaches to the study of property behavior: evolutionary
      game theory, ethology, comparative cognition, and developmental psychology.
      Finally, we propose an empirical study, using an ethological approach to test the
      presence of property and possessive behavior in a natural setting, using our
      closest living relative, the chimpanzee (Pan troglodytes). Overall, we argue that
      this field of research is at a turning point, where the novel integration of
      various methods may provide an explanation to the origin of property.

PMID- 30290032
TI  - Family characteristics and children's knowledge on cardiovascular risk factors.
AB  - BACKGROUND: Cardiovascular disease has the highest mortality rates than any other
      disease globally. Some major risk factors seem to be established in early stages
      of life suggesting preventive strategies as a major mean to reduce cardiovascular
      mortality. The aim of the present work was to investigate the role of
      socioeconomic status and family characteristics on children's knowledge and
      perceptions concerning cardiovascular disease risk factors. METHODS: A cross
      sectional survey was conducted among 1728 children (46% male) aged 10 to 12
      years, attending Greek primary schools in Athens, Heraklion (the capital City of
      the Island of Crete), Kalamata, Pyrgos and Sparti (Peloponnese peninsula),
      Greece. Sampling was conducted on school premises, during the school-years 2014
      15 and 2015-16 (participation rate: 95-100%). Data were collected through a self
      administered, anonymous questionnaire. Children's knowledge concerning various
      issues related to cardiovascular risk, such as nutrition, physical activity and
      smoking was also examined. Data concerning family characteristics were collected
      through another questionnaire completed by parents. RESULTS: Paternal educational
      level and living with both parents instead of single-parent upbringing, were
      positively associated with children's knowledge regarding cardiovascular risk
      factors (b=0.42 (95%CI 0.01, 0.83), p=0.04 and b=0.78 (95%CI 0.013, 1.43), p=0.02
      respectively). Moreover, children with more siblings seemed to have less
      sufficient knowledge compared to their peers who had fewer siblings (b per 1
      sibling =-0.24 (95%CI -0.47, -0.014), p=0.04). CONCLUSIONS: The aforementioned
      findings enhance the link between the micro-environment and children's knowledge
      and perceptions concerning cardiovascular health, providing information to health
      care professionals while counseling youths. This article is protected by
      copyright. All rights reserved.

PMID- 30290034
TI  - Clinicopathological features of immunoglobulin G4-related pleural lesions and
      diagnostic utility of pleural effusion cytology.
AB  - OBJECTIVE: Immunoglobulin (Ig)G4-related disease is a recently described systemic
      immune-mediated fibro-inflammatory disease that frequently occurs in tumorous
      form. Herein, we elucidated the clinicopathological and cytological
      characteristics of IgG4-related pleural lesions (PLs). PATIENTS AND METHODS:
      Among 22 patients with fibro-inflammatory PLs of idiopathic aetiology, eight
      cases were diagnosed as IgG4-PL and the remaining 14 as non-IgG4-PL according to
      comprehensive diagnostic criteria for IgG4-related disease. Cell block
      examination of pleural effusion (CBPE) was performed in five patients with IgG4
      PL and in six with non-IgG4-PL. Both groups were compared in terms of clinical
      presentation, laboratory data, histopathological features of resected pleura, and
      cytological features of pleural effusion (PE). RESULTS: PE was the most common
      (six patients, 75%) clinical presentation of IgG4-PL. IgG4-PL comparatively
      showed significantly more frequent concomitant allergic disease (P = .021),
      higher serum IgE levels (P = .012), higher adenosine deaminase levels in pleural
      fluid (P = .005), and rare spontaneous recovery without treatment (P = .046). The
      IgG4-PL group was histologically characterised by thicker fibrous pleura,
      storiform fibrosis, and infiltration of regulatory T cells, eosinophils and
      basophils. Using CBPE, IgG4-PL was cytologically distinct with numerous IgG4+
      cells and eosinophils. The cytology of CBPE positively correlated with the
      histology of pleural tissue in the number of IgG4+ cells and eosinophils (R =
      .769 and .803, respectively). CONCLUSION: IgG4-PL frequently presents with PE and
      is histologically and cytologically characterised by abundant infiltration of
      IgG4+ cells and eosinophils. We believe that CBPE with
      immunohistochemistry/special staining could assist in the auxiliary diagnosis of
      IgG4-PL.

PMID- 30290033
TI  - Urea transport B gene induces melanoma B16 cell death via activation of p53 and
      mitochondrial apoptosis.
AB  - Urea Transporter B (UT-B) is a membrane channel protein that mediates the rapid
      transmembrane transport of urea and participates in urine concentration. Urea
      Transporter B is expressed in skin, but we found that there is little expression
      in human melanoma tissue. In this study, we examined the effects of UT-B
      overexpression in melanoma. The results indicated that there is no UT-B mRNA
      expression in B16 cells, and UT-B overexpression repressed B16 cell proliferation
      and induced apoptosis in vitro. We show that UT-B overexpression causes increased
      reactive oxygen species production, which may be caused by mitochondria
      dysfunction. The mitochondrial membrane potential (PsiDeltam) was lower in UT-B
      overexpressing B16 cells. The proteins involved in complexes I, III, IV and V of
      the respiratory chain were clearly downregulated in UT-B-overexpressing B16
      cells, which would strongly reduce the activity of the electron transport chain.
      We found that mitochondrial release of cytochrome C into the cytoplasm also
      increased, indicating that apoptosis had been activated. In addition, UT-B
      overexpression reduced AKT phosphorylation and MDM2 expression and increased p53
      expression; p53 activation may be involved in the anticancer effects of UT-B
      overexpression. Urea Transporter B overexpression also inhibited tumor growth in
      vivo. In conclusion, we demonstrated that UT-B may be related to the occurrence
      of melanoma and play a role in tumor development.

PMID- 30290035
TI  - Team-based parent training by child specialists helps maltreated children.
AB  - BACKGROUND: This study assessed the effects of the Parent Training (PT)
      technique, in which child specialists (CSs) such as preschool- and school
      teachers promote secure attachment in children with aberrant social behavior
      following maltreatment, using a team approach. METHODS: CSs confirmed the
      presence of child abuse, according to Japanese Ministry of Health, Labour and
      Welfare criteria. CSs such as homeroom, special education-related, student
      guidance-related, nursing teachers and co-workers received a PT course conducted
      by the authors. A homeroom teacher provided classroom management to model good
      examples of social life for the target child. A nursing teacher and assistant
      offered individualized instruction to foster the formation of secure attachments
      by the target child. RESULT: Behavioral abnormalities in both school and home
      resolved in 7 out of 12 cases. These cases received the intervention for 2 to 4
      years. In the other cases, behavioral abnormalities disappeared or decreased in
      school, but continued at home. Almost all children met the alternative criteria
      of attachment disorder proposed by Borris and Zeanah. One child met the criteria
      for reactive attachment disorder (DSM-IV). This intervention is significantly
      more effective for children who have yet to begin elementary school than those in
      elementary school. CONCLUSIONS: This study indicates that the PT technique as
      applied by CSs using a team approach may be a useful intervention for fostering
      secure attachment in children with maltreatment who exhibit behavioral
      abnormalities. Early detection and intervention are necessary successfully to
      address the behavioral abnormalities of children with maltreatment. This article
      is protected by copyright. All rights reserved.

PMID- 30290036
TI  - A Systematic Study of Selective Protein Glycation.
AB  - Glycation is a non-enzymatic post-translational modification (PTM) that remains
      poorly understood, largely because it is unknown how it occurs selectively. Using
      mass spectrometry, it was possible to evaluate total glycation levels, identify
      distinct glycated products, assign unique glycation sites, and correlate these
      data with chemical and structural features for a panel of proteins glycated in
      vitro. It was determined that the extent of glycation does not correlate with pKa
      or surface exposure at reactive sites. Rather, the data reveal that primary
      sequence dictates the overall likelihood that a site will become glycated, while
      surrounding structure further sculpts the glycation outcome. Clustered acidic
      residues were found to prevent glycation, whereas a combination of tyrosine and
      polar residues appear to promote glycation. This work contributes important new
      knowledge about the molecular features that govern selective glycation.

PMID- 30290037
TI  - Testing the role of the posterior cingulate cortex in processing salient stimuli
      in cannabis users: an rTMS study.
AB  - The posterior cingulate cortex (PCC) and precuneus are hubs in the default mode
      network and play a role in processing external salient stimuli. Accordingly,
      activation in these regions has been associated with response to salient stimuli
      using drug cue-reactivity paradigms in substance using populations. These studies
      suggest that the PCC and precuneus may underlie deficits in processing salient
      stimuli that contribute toward the development of substance use disorders. The
      goal of this study was to directly test this hypothesis using repetitive
      transcranial magnetic stimulation (rTMS). Using a double-blind, placebo
      controlled design, we used rTMS to target the PCC and precuneus with a double
      cone coil at 10 Hz (high frequency) and 1 Hz (low frequency) in 10 adult cannabis
      users and 10 age- and sex-matched non-using controls. Electroencephalography data
      were collected before and after rTMS during a modified oddball paradigm with
      neutral, oddball, self-relevant, and cannabis-related stimuli. Cannabis users
      exhibited increased amplitude in P3 and faster latencies in the P3, N2, and P2
      components in response to self-relevant stimuli compared to controls during
      baseline that normalized after rTMS. These results suggest that cannabis users
      exhibited heightened salience to external self-relevant stimuli that were
      modulated after rTMS. PCC dysfunction in cannabis users may be related to
      abnormalities in processing salient stimuli, such those during cue-reactivity,
      and provides a potential target for cannabis use disorder intervention.

PMID- 30290039
TI  - Double quantum filtered 23 Na MRI with magic angle excitation of human skeletal
      muscle in the presence of B0 and B1 inhomogeneities.
AB  - Double quantum filtered 23 Na MRI with magic angle excitation (DQF-MA) can be
      used to selectively detect sodium ions located within anisotropic structures such
      as muscle fibers. It might therefore be a promising tool to analyze the
      microscopic environment of sodium ions, for example in the context of osmotically
      neutral sodium retention. However, DQF-MA imaging is challenging due to various
      signal dependences, on both measurement parameters and external influences. The
      aim of this work was to examine how B0 in combination with B1 inhomogeneities
      alter the DQF-MA signal intensity. We showed that, in the presence of B0
      inhomogeneities, flip angle schemes with only one 54.7 degrees  pulse can be
      favorable compared with the classical 90 degrees -54.7 degrees -54.7 degrees 
      scheme. DQF-MA images of the human lower leg were acquired at B0  = 3 T with a
      nominal spatial resolution of 12 * 12 * 36 mm3 within an acquisition time of TAcq
      < 10 min, and compared with spin density weighted (DW), as well as triple
      quantum filtration (TQF) 23 Na images. We found mean normalized signal-to-noise
      ratios of TQF/DW = 13.7 +/- 2.3% (tibialis anterior), 11.9 +/- 2.3% (soleus) and
      11.4 +/- 2.2% (gastrocnemius medialis), as well as DQF-MA/DW = 4.7 +/- 1.1%
      (tibialis anterior), 3.3 +/- 0.73% (soleus) and 3.4 +/- 0.6% (gastrocnemius
      medialis). These ratios might serve as additional measures in future clinical
      studies of sodium retention within human skeletal muscle. However, the influence
      of B0 and B1 inhomogeneities should be considered when interpreting DQF-MA
      images.

PMID- 30290040
TI  - Atypical chronic lymphocytic leukemia: Brief historical overview and current
      usage of an equivocal concept.

PMID- 30290038
TI  - A group of long noncoding RNAs identified by data mining can predict the
      prognosis of lung adenocarcinoma.
AB  - Long noncoding RNAs (lncRNA) are reported to be potential cancer biomarkers. This
      study aims to find new lncRNA biomarker relevant to lung adenocarcinoma. Gene
      expression profile and clinical data of lung adenocarcinoma and lung squamous
      cell carcinoma patients were downloaded from the UCSC Xena database. These data
      were analyzed to identify potential lncRNA prognostic biomarkers, and the
      candidate lncRNAs were analyzed and verified with association analysis, meta
      analysis, survival analysis, gene ontology analysis, gene set enrichment
      analysis, and other statistical methods. A group of 5 lncRNAs was identified from
      the 1965 differentially expressed (fold-change >2) genes. Four of these 5 lncRNAs
      were expressed at a lower level in lung adenocarcinoma tissues and the other one
      at a higher level (P < .0001). A risk score model was constructed using a linear
      combination of the expression levels of these lncRNAs. High-risk patients showed
      poorer overall survival (hazard ratio [HR] = 2.14; 95% confidence interval [CI],
      1.67-3.06, P < .0001), disease-free survival (HR = 1.84; 95% CI, 1.26-2.35, P =
      .0007), and recurrence-free survival (HR = 1.51; 95% CI, 1.02-2.40, P = .04). The
      5-fold cross-validation and subsequent meta-analysis further verified that
      patients in the low-risk group had better survival (95% CI, 0.74-1.79, Z = 4.72,
      P < .00001). Furthermore, both univariate and multivariate Cox regression
      analyses revealed that the prognostic value of these 5 lncRNAs was independent of
      other clinical prognostic factors. Further analysis indicated that these 5
      lncRNAs might be associated with tumor metastasis. Taken together, our study
      suggests new prognostic lncRNA biomarkers for lung adenocarcinoma.

PMID- 30290041
TI  - Lymphadenitis by Non-tuberculous Mycobacteria in children.
AB  - BACKGROUND: Non-tuberculous Mycobacteria (NTM) constitute an important cause of
      cervical lymphadenitis in immunocompetent children. In this study we aimed at
      estimating the incidence of lymphadenitis due to NTM in children in Cyprus and
      describe the characteristics, diagnostic approaches, management and outcomes of
      such infections. METHODS: Children between the ages 1 to 5 years old, evaluated
      at our hospital from January 1st 2007 to December 31st 2016 for lymphadenopathy
      were included in the study. All children had a positive culture of a lymph node
      specimen for non-tuberculous Mycobacteria. RESULTS: A total of 22 cases of
      culture-positive lymphadenitis caused by NTM were reviewed. The patients' age
      ranged from 16 to 55 months. The tuberculin skin test revealed an induration in
      81.0% of cases (diameter ranging from 4 - 17mm). M. avium was isolated in
      seventeen cases (77.3%), M. intracellulare in three (13.6%), M. paraffinicum in
      one (4.5%) and M. Kasansii in one case (4.5%). All 22 patients underwent surgical
      excision of affected nodes. Additional anti-mycobacterial treatment was given
      when complete excision was not achieved or for post-surgical recurrence.
      Complications were few and included scars in 3 children and a case of transient
      facial nerve palsy. CONCLUSION: Surgical excision of the infected lymph nodes by
      NTM is an effective diagnostic and therapeutic approach. In cases when total
      surgical excision is not feasible, a combination of partial excision with a
      clarithromycin including drug regimen appears safe, effective and causes milder
      and fewer complications as a result of surgery. This article is protected by
      copyright. All rights reserved.

PMID- 30290042
TI  - Copper-Catalyzed Transsulfinamidation of Sulfinamides as a Key Step in the
      Preparation of Sulfonamides and Sulfonimidamides.
AB  - Secondary or tertiary sulfinamides are prepared by copper-catalyzed
      transsulfinamidation of primary sulfinamides with O-benzoyl hydroxylamines.
      Subsequent oxidations of the resulting products lead to the corresponding
      sulfonamides. Treatment of N-aryl sulfinamides with O-benzoyl hydroxylamines
      under copper catalysis provides N-aryl sulfonimidamides.

PMID- 30290043
TI  - Role of Noxa in proliferation, apoptosis, and autophagy in human adenoid cystic
      carcinoma.
AB  - BACKGROUND: Noxa, which is subset of the Bcl-2 family of proteins, was previously
      reported to have considerable therapeutic potential in diverse cancers. However,
      its expression and role in salivary gland adenoid cystic carcinoma (ACC) have not
      been well studied. This study aimed to elucidate the expression and role of Noxa
      in salivary gland ACC. MATERIALS AND METHODS: The expression levels of NOXA and
      its association with overall survival in salivary gland ACC were analyzed by
      quantitative real-time PCR. We next examined the effects of Noxa overexpression
      or inhibition on colony formation, proliferation, apoptosis, and autophagy of
      salivary gland ACC cells. Furthermore, promoter analysis was performed to
      identify the potential transcriptional activator of NOXA. RESULTS: NOXA was
      markedly down-regulated and significantly correlated with a more aggressive
      phenotype and poor overall survival of salivary gland ACC. Ectopic expression of
      Noxa suppressed the viability and growth of ACC cells, which involved the
      induction of apoptosis and autophagy. Moreover, the transcriptional activity of
      NOXA gene could be enhanced by p53. CONCLUSION: The findings of this study
      indicate that Noxa, activated transcriptionally by p53, suppress the progression
      of ACC, whereby it regulates proliferation, apoptosis, and autophagy.

PMID- 30290045
TI  - Mild Homologation of Esters through Continuous Flow Chloroacetate Claisen
      Reactions.
AB  - The selective chloromethylenation of functionalized esters using chloroacetic
      acid (CA) and LiHMDS (HMDS=hexamethyldisilazide) in a continuous-flow setup is
      reported. This Claisen homologation is for the first time extended to bis
      chloromethylenation using dichloroacetic acid (DCA), thus giving access to under
      explored alpha,alpha'-bis-chloroketones. The use of flow conditions enables
      efficient generation and reaction of the unstable chloroacetate dianion
      intermediates, leading to unprecedented mild and scalable reaction conditions at
      an economical reagent stoichiometry (-10  degrees C, <1 min, 1.0-2.4 equiv
      dianion). The clean reaction profiles allow subsequent use of the unpurified
      crude products, which is demonstrated in the synthesis of various heterocycles of
      broad interest. Furthermore, we report a novel, catalyst-free substitution of the
      obtained monochloro ketone products with (hetero)aryl zinc enolates to give
      valuable 1,4-diketones.

PMID- 30290044
TI  - Kernel Homology in Gold Nanoclusters.
AB  - Homology is well known in organic chemistry; however, it has not yet been
      reported in nanochemistry. Herein, we introduce the concept of kernel homology to
      describe the phenomenon of metal nanoclusters sharing the same "functional group"
      in kernels with some similar properties. To illustrate this point, we synthesized
      two novel gold nanoclusters, Au44 (TBBT)26 and Au48 (TBBT)28 (TBBTH=4-tert
      butylbenzenethiol), and solved their total structures by X-ray crystallography,
      which reveals that they have the same Au23 bi-icosahedron capped with a similar
      bottom cap (Au6 and Au8 , respectively) in the kernels. The two novel gold
      nanoclusters, together with the existing Au38 (PET)24 nanocluster
      (PETH=phenylethanethiol), have the same "functional group"-Au23 -in their kernels
      and have some similar properties (e.g., electrochemical properties); therefore,
      they are comparable to the homologues in organic chemistry.

PMID- 30290046
TI  - Biomimetic DNA Nanotubes: Nanoscale Channel Design and Applications.
AB  - Biomacromolecular nanotubes play important physiological roles in transmembrane
      ion/molecule channeling, intracellular transport and inter-cellular
      communications. While genetically encoded protein nanotubes are predominant in
      vivo, the in vitro construction of biomimetic DNA nanotubes has attracted intense
      interest with the rise of structural DNA nanotechnology. The abiotic use of DNA
      assembly provides a powerful bottom-up approach for the rational construction of
      complex materials with arbitrary size and shape at the nanoscale. More
      specifically, a typical DNA nanotube can be assembled either with parallel
      aligned DNA duplexes or by closing DNA tile lattices. These artificial DNA
      nanotubes can be tailored and site-specifically modified to realize biomimetic
      functions including ionic or molecular channeling, bioreactors, drug delivery and
      biomolecular sensing. In this Minireview, we aim to summarize recent advances in
      design strategies, including the characterization and applications of biomimetic
      DNA nanotubes.

PMID- 30290047
TI  - Risk factors and epidemiology of pediatric ventriculoperitoneal shunt infections.
AB  - AIM: To identify independent risk factors for cerebrospinal fluid (CSF) shunt
      infection. METHODS: The medial records of all patients aged 0-18 years that
      underwent shunt-related surgeries for the treatment of hydrocephalus at our
      institution between January 1996 and December 2015 were reviewed. For each case,
      2 randomly selected controls with no shunt infection were chosen. Demographic
      clinical and microbiological data were abstracted. RESULTS: A total of 1570 shunt
      related procedures met the inclusion criteria, yielding 68 infections (in 63
      patients). The control group included 132 infection-free patients. The average
      annual infection rate was 4.2% cases per year. The median time between shunt
      procedures to infection was 19 days (range 1-2181). In multivariate analysis,
      risk factors associated with increased risk to develop an infection included:
      children who had two or more previous revisions in (odds ratio (OR) 4.8;
      95%confidence interval (CI) 1.5-15.9), age of less than 5 years (OR 4.5; 95%CI
      1.5-13.4). A neoplastic etiology for hydrocephalus was found to be a protective
      factor (p = 0.001) for shunt infection. CONCLUSIONS: A history of shunt revision
      was the most significant risk factor in the development of subsequent shunt
      infection. Age above 5 years was found to be a protective factor. Future efforts
      should focus on modalities to optimize revision procedures and reduce risks of
      subsequent infection This article is protected by copyright. All rights reserved.

PMID- 30290048
TI  - "Printing" DNA Strand Patterns on Small Molecules with Control of Valency,
      Directionality, and Sequence.
AB  - The incorporation of synthetic molecules as corner units in DNA structures has
      been of interest over the last two decades. In this work, we present a facile
      method for generating branched small molecule-DNA hybrids with controllable
      valency, different sequences, and directionalities (5'-3') using a "printing"
      process from a simple 3-way junction structure. We also show that the DNA
      imprinted small molecule can be extended asymmetrically using polymerase chain
      reaction (PCR) and can be replicated chemically. This strategy provides
      opportunities to achieve new structural motifs in DNA nanotechnology and
      introduce new functionalities to DNA nanostructures.

PMID- 30290050
TI  - Deaminative Borylation of Aliphatic Amines Enabled by Visible Light Excitation of
      an Electron Donor-Acceptor Complex.
AB  - A deaminative strategy for the borylation of aliphatic primary amines is
      described. Alkyl radicals derived from the single-electron reduction of redox
      active pyridinium salts, which can be isolated or generated in situ, were
      borylated in a visible light-mediated reaction with bis(catecholato)diboron. No
      catalyst or further additives were required. The key electron donor-acceptor
      complex was characterized in detail by both experimental and computational
      investigations. The synthetic potential of this mild protocol was demonstrated
      through the late-stage functionalization of natural products and drug molecules.

PMID- 30290049
TI  - Forkhead box C1 boosts triple-negative breast cancer metastasis through
      activating the transcription of chemokine receptor-4.
AB  - The transcription factor forkhead box C1 (FOXC1) has recently been proposed as a
      crucial regulator of triple-negative breast cancer (TNBC) and associated with
      TNBC metastasis. However, the mechanism of FOXC1 in TNBC development and
      metastasis is elusive. In this study, overexpression of FOXC1 in MDA-MB-231 cells
      significantly enhanced, whereas knockdown of FOXC1 in BT549 cells significantly
      reduced, the capabilities of TNBC cell invasion and motility in vitro and
      metastasis to the lung in vivo, when compared to their respective control cells.
      Mechanistic studies revealed that FOXC1 increased the expression of CXC chemokine
      receptor-4 (CXCR4), probably through transcriptional activation. AMD3100, an
      inhibitor of CXCR4, could block cell migration. In a zebrafish tumor model,
      AMD3100 could suppress cell invasion and metastasis. In addition, overexpressing
      CXCR4 in FOXC1-knockdown BT549 cells increased the capabilities of TNBC cell
      invasion and motility. In contrast, inhibition of CXCR4 with either AMD3100 or
      siRNA in MDA-MB-231 cells overexpressing FOXC1 reduced the capabilities of
      invasion and motility. Taken together, our results reveal a potential mechanism
      for FOXC1-induced TNBC metastasis.

PMID- 30290051
TI  - Enantioselective Synthesis of Phthalides and Isochromanones via Heck-Matsuda
      Arylation of Dihydrofurans.
AB  - In this communication, the enantioselective synthesis of phthalides and
      isochromanones is described through a new palladium-catalyzed Heck-Matsuda
      arylation/NaBH4 -reduction/lactonization sequence of 2,3- and 2,5-dihydrofurans
      in good overall yields and excellent enantioselectivities (up to 98:2 er). This
      expeditious synthesis of chiral Heck lactol intermediates allowed the
      diversification of the strategy to obtain medicinally relevant chiral lactones,
      amines, and olefins. The natural product 3-butylphthalide was obtained in three
      steps with an overall yield of 33 % yield in 98:2 er.

PMID- 30290052
TI  - Effectiveness of Primary Care Interventions Using a Biopsychosocial Approach in
      Chronic Low Back Pain: A Systematic Review.
AB  - BACKGROUND AND OBJECTIVE: Recent systematic reviews show promising effects for
      multidisciplinary biopsychosocial (BPS) interventions in patients with chronic
      low back pain (CLBP). Nowadays, BPS interventions have also been developed for
      primary care physiotherapy settings. Our aim was to systematically review the
      evidence on the effectiveness of primary care BPS interventions in improving
      functional disability, pain, and work status for patients with CLBP. Secondly, we
      aimed to provide an elaborated overview of BPS intervention designs,
      physiotherapist training programs, and process-related factors (practical
      implementation). METHODS: We searched in scientific databases and reference
      lists. Randomized controlled trials (RCTs) evaluating primary care
      physiotherapist-led BPS interventions in adults (>=18 years) with nonspecific
      CLBP (>=12 weeks) were included. RESULTS: Our search resulted in 943 references;
      7 RCTs were included (1,426 participants). Results show moderate-quality evidence
      (3 trials; 991 participants) that a BPS intervention is more effective than
      education/advice for reducing disability and pain in the short, medium, and long
      term. Low-quality evidence (4 trials; 435 participants) was found for no
      difference with physical activity treatments. CONCLUSIONS: BPS interventions seem
      more effective than education/advice and were found to be as effective as
      physical activity interventions in patients with CLBP. BPS interventions with a
      clear focus on psychosocial factors (understanding pain, unhelpful thoughts,
      coping styles, and goal setting) seem most promising. Sufficient delivery of BPS
      elements is expected when physiotherapists participate in training programs with
      extensive support prior and during delivery (manual, supervision, and informative
      resources).

PMID- 30290053
TI  - Sequences of Sequences: Spatial Organization of Coded Matter through Layer-by
      Layer Assembly of Digital Polymers.
AB  - A library of 16 digitally encoded polyanions was used in a layer-by-layer (LbL)
      polyelectrolyte assembly to nanofabricate thin films containing digitally coded
      strata. The polyanions were digital polyphosphodiesters (d-PPDE) prepared via an
      automated phosphoramidite process. Each component of the library contained 10
      bytes of ASCII-encoded text (i.e. 80 coded monomers); thus the entire library
      allows the writing of a full sentence, which can be stored in a multilayer film
      as a sequence of sequences. To prepare fully segregated digital domains, non
      coded layers composed of poly(allylamine hydrochloride) (PAH)/poly(sodium 4
      styrenesulfonate) (PSS) were included between the d-PPDE coded layers as an
      intermediate barrier. Detailed analysis of the film homogeneity indicated
      formation of 70 nm-thick films in which digital layers are kept apart from
      another by non-coded interlayers. As a result, the sequence-coded polymer library
      could be piled-up in a defined sequence of layers.

PMID- 30290055
TI  - Overview of sample introduction techniques prior to GC for the analysis of
      volatiles in solid materials.
AB  - Sample preparation and introduction techniques are very critical steps in gas
      chromatography analysis and particularly in the analysis of volatiles in solid
      samples. In these cases, they can be divided into two main categories: direct and
      indirect approaches, based on how the solid sample is treated, i.e. with and
      without dissolution (or extraction) of analytes from the solid sample. To enable
      routine application, coupling with sample preparation techniques (especially
      solid or solvent-based microextractions) is needed to achieve automation. Here,
      an overview of the most common sample introduction techniques for gas
      chromatography with their advantages and drawbacks is presented and discussed,
      including references to relevant examples. So, this review can serve as guidance
      for new users.

PMID- 30290054
TI  - Possible role of p53/Mieap-regulated mitochondrial quality control as a tumor
      suppressor in human breast cancer.
AB  - Mitochondria-eating protein (Mieap), encoded by a p53-target gene, plays an
      important role in mitochondrial quality control (MQC). Mieap has been reported to
      have a critical role in tumor suppression in colorectal cancer. Here, we
      investigated its role as a tumor suppressor in breast cancer. The enforced
      expression of exogenous Mieap in breast cancer cells induced caspase-dependent
      apoptosis, with activation of both caspase-3/7 and caspase-9.
      Immunohistochemistry revealed endogenous Mieap in the cytoplasm in 24/75 (32%)
      invasive ductal carcinomas (IDC), 15/27 (55.6%) cases of ductal carcinoma in situ
      (DCIS) and 16/18 (88.9%) fibroadenomas (FA) (IDC vs DCIS; P = 0.0389, DCIS vs FA;
      P = 0.0234, IDC vs FA; P < 0.0001). In IDC, the Mieap promoter was methylated in
      6/46 (13%) cases, whereas p53 was mutated in 6/46 (13%) cases. Therefore, the
      p53/Mieap-regulated MQC pathway was inactivated in 12/46 IDC (26.1%).
      Interestingly, all tumors derived from the 12 patients with Mieap promoter
      methylation or p53 mutations pathologically exhibited more aggressive and
      malignant breast cancer phenotypes. Impairment of p53/Mieap-regulated MQC pathway
      resulted in significantly shorter disease-free survival (DFS) (P = 0.021),
      although p53 status is more prognostic in DFS than Mieap promoter methylation.
      These results indicate that p53/Mieap-regulated MQC has a critical role in tumor
      suppression in breast cancer, possibly in part through mitochondrial apoptotic
      pathway.

PMID- 30290056
TI  - Response anisocoria in the pupillary light and darkness reflex.
AB  - The pupil constricts or dilates in response to a luminance increase or decrease,
      and these transient pupillary responses are controlled by the parasympathetic and
      sympathetic pathways. Although pupillary responses of the two eyes are highly
      correlated, they are not always identical (referred to as anisocoria). For
      example, there are unequal direct and consensual pupillary constriction responses
      after an increase in luminance to one eye. While contraction anisocoria (i.e.
      constriction) has been demonstrated in the pupillary light reflex, it is not yet
      known if there is also dilation anisocoria in the pupillary darkness reflex.
      Unlike previous studies that focused on the pupillary light reflex, we examined
      response anisocoria in both pupillary light and darkness reflexes. While
      requiring participants to maintain central fixation, we presented a light or dark
      stimulus to either the right or left visual field to induce transient pupillary
      constriction or dilation. Both the pupillary light and darkness reflexes had
      significantly larger ipsilateral responses compared to the contralateral
      responses relative to the stimulated visual field. The observed ipsilateral
      effects occurred significantly faster in the light than darkness reflex,
      suggesting that larger ipsilateral pupillary dilation after a luminance decrease
      cannot be only attributed to the inhibition of the parasympathetic system, but is
      also mediated by the excitation of the sympathetic system. Together, our results
      demonstrated a larger ipsilateral pupil response in both the pupillary light and
      darkness reflex, indicating an asymmetry in ipsilateral and contralateral neural
      circuitry of the pupillary darkness reflex.

PMID- 30290057
TI  - Osteophytes in the Cervical Vertebral Bodies (C3-C7)-Demographical Perspectives.
AB  - Vertebral osteophytes are an age-dependent manifestation of degenerative changes
      in the spine. We aimed to determine the prevalence and severity of cervical
      osteophytosis in a large study population. To do so, we developed a grading
      system for osteophytosis, enabling the assessment of their presence and severity
      in the cervical spine, and applied it to the analysis of dried cervical vertebral
      bodies (C3-C7) from 273 individuals. Statistical analyses were carried out per
      motion segment, while testing for the effect of age, sex, and ethnicity. The
      highest prevalence of osteophytes was found in motion segment C5/C6 (48.2%),
      followed by C4/C5 (44.1%), and last C6/C7 and C3/C4 (40.5%). Severe osteophytes
      are most commonly seen in motion segment C5/C6. In all motion segments, the
      inferior discal surface of the upper vertebra manifests more osteophytes than the
      superior discal surface of the lower one. Osteophytes prevalence is sex-dependent
      only in the upper cervical vertebrae (C3-C4), and age- and ethnicity-dependent
      for all vertebrae. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30290058
TI  - An in vitro and in vivo study of the role of long non-coding RNA-HOST2 in the
      proliferation, migration, and invasion of human glioma cells.
AB  - Gliomas are the most commonly occurring primary malignant brain tumors in the
      central nervous system of adults. They are rarely curable and the prognosis for
      high grade gliomas is generally poor. Recently, long non-coding RNA (lncRNA)
      human ovarian cancer-specific transcript 2 (HOST2) has been reported to be
      expressed at high levels in human ovarian cancer, involving tumorigenesis.
      However, little is still known about whether and how HOST2 regulates glioma
      development and progression. Therefore, this study aims to investigate the role
      of HOST2 in human glioma cells. Reverse transcription quantitative real-time
      polymerase chain reaction (RT-qPCR) was used to determine the expression of
      lncRNA HOST2, let-7b, and PBX3 in human glioma cells. Cultured human glioma cells
      were treated with siRNA (si)-lncRNA HOST2, let-7b mimic, si-lncRNA HOST2 + let-7b
      inhibitor, and si-PBX3. Parameters including cell viability, colony formation,
      cell migration, and cell invasion were detected by cell counting kit-8 assay,
      colony formation assay, scratch test, and Transwell assay respectively to
      determine the effects of down-regulated HOST2 on glioma cells. Tumor formation in
      nude mice was evaluated by subcutaneous tumor formation experiment. Results
      showed that HOST2 and PBX3 were highly expressed in glioma tissue whereas let-7b
      was expressed at much lower levels. In response to treatment with si-lncRNA
      HOST2, si-PBX3, and let-7b mimic, glioma cell lines exhibited decreased cell
      viability, suppressed cell migration, invasion, and reduced colony formation of
      glioma cells. This was accompanied by an attenuated tumor formation with smaller
      volume and weight in nude mice, suggesting that down-regulated HOST2 could
      inhibit the tumorigenicity of glioma cells. Lastly, we found that lncRNA HOST2
      was highly expressed in glioma tissues and its down-regulation could inhibit the
      growth and invasion of glioma cells. (c) 2018 IUBMB Life, 2018.

PMID- 30290059
TI  - Critical evaluation of microextraction pretreatment techniques - Part 1: Single
      drop and sorbent-based techniques.
AB  - Sample pretreatment techniques or preconcentration constitute a very important
      step before the analysis of environmental, clinical, pharmaceutical, and other
      complex samples. Thanks to extraction techniques it is possible to achieve higher
      method sensitivities and selectivities. Miniaturization microextraction methods
      make them more environmentally friendly and only small amounts of samples are
      required. In the past 30 years, a number of microextraction methods have been
      developed and used and are documented in thousands of articles. Many reviews have
      been written focusing on their use in specified professional fields or on the
      latest trends. Unfortunately, no uniform nomenclature has been introduced for
      these methods. Therefore, this review attempts to classify all the essential
      microextraction techniques and describes their advantages, disadvantages, and the
      latest innovations. The methods are divided into two main groups: single drop and
      sorbent-based techniques according to the type of extraction phase.

PMID- 30290060
TI  - Aqueous Dual-Ion Battery Based on a Hematite Anode with Exposed {1 0 4} Facets.
AB  - The aqueous rechargeable lithium battery (ARLB) is one of the most promising
      devices for large-scale grid applications. Currently, a key issue for ARLBs is to
      develop promising anode materials with favorable electrochemical performances.
      Here, for the first time, we demonstrate an aqueous battery that utilizes the
      reversible redox reaction with hydroxide ions (OH- ) in the hematite (Fe2 O3 )
      anode and a commercial Li ion intercalation compound in neutral solution as the
      cathode. The fabricated aqueous battery displays a reversible capacity of 92 mAh
      g-1 . The morphology of the used Fe2 O3 anode with exposed {1 0 4} facets for
      this aqueous battery is unique and attractive. Importantly, with the dual-pH
      neutral-alkaline hybrid electrolyte, many excellent anode materials that
      previously could only work in alkaline electrolytes can now be successfully
      combined with commercial cathodes in neutral solutions, which may significantly
      enrich the range of anode materials for ARLBs. In addition, the reported battery
      configuration can be extended to other aqueous batteries beyond Li-ion ones with
      lower cost.

PMID- 30290061
TI  - Early administration of dapagliflozin preserves pancreatic beta-cell mass through
      a legacy effect in a mouse model of type 2 diabetes.
AB  - AIMS/INTRODUCTION: The preservation of pancreatic beta-cell mass is an essential
      factor in the onset and development of type 2 diabetes mellitus. Recently, sodium
      glucose cotransporter 2 inhibitors have been launched as antihyperglycemic
      agents, and their organ-protective effects are attracting attention. They are
      also reported to have favorable effects on the preservation of pancreatic beta
      cell mass, but the appropriate timing for the administration of sodium-glucose
      cotransporter 2 inhibitors is obscure. MATERIALS AND METHODS: In the present
      study, we administered a sodium-glucose cotransporter 2 inhibitor, dapagliflozin,
      to an animal model of type 2 diabetes mellitus, db/db mice, and investigated the
      adequate timing and duration for its administration. We also carried out
      microarray analysis using pancreatic islets from db/db mice. RESULTS: We found
      that dapagliflozin preserved pancreatic beta-cell mass depending on the duration
      of administration and markedly improved blood glucose levels. If the duration was
      the same, the earlier administration of dapagliflozin was more effective in
      preserving pancreatic beta-cell mass, increasing serum insulin levels and
      improving blood glucose levels. From microarray analysis, we discovered that the
      expression of Agr2, Tff2 and Gkn3 was significantly upregulated after the early
      administration of dapagliflozin. This upregulated gene expression might provide a
      legacy effect for the preservation of pancreatic beta-cell mass. CONCLUSIONS: We
      expect that the early administration of dapagliflozin would provide a long
      lasting effect in preserving pancreatic beta-cell mass.

PMID- 30290062
TI  - Exploring the C-Terminal Tail Dynamics: Structural and Molecular Perspectives
      into the Therapeutic Activities of Novel CRMP-2 Inhibitors, Naringenin and
      Naringenin-7-O-glucuronide, in the Treatment of Alzheimer's Disease.
AB  - The collapsin response mediator protein (CRMP-2) is hyperphosphorylated in
      Alzheimer's disease (AD). These phosphorylation events are mediated by specific
      kinase proteins, GSK3beta and Cdk5, and occur at target phosphorylation sites
      majorly located at the C-terminal tail of CRMP-2. The abilities of naringenin
      (NAR) and naringenin-7-O-glucuronide (NAR-7-O-G) to selectively bind CRMP-2 and
      reduce its phosphorylation have been previously demonstrated; the molecular
      interplay between these events remains unresolved. Using computational tools, we
      unravel the possible mechanisms by which these molecules disrupt CRMP-2
      phosphorylation. Structural and dynamic analyses revealed that while the C
      terminal tail of unbound CRMP-2 was extended and subtly organized, notable
      conformational disarray and rigidity characterized this region when bound by NAR
      and NAR-7-O-G. Consequentially, atomistic motions of constituent phosphorylation
      sites were restricted, indicative of structural occurrences that could distort
      the accessibility of interactive kinase proteins. A similar pattern was observed
      at a target phosphorylation site located in the globular domain of CRMP-2.
      MM/PBSA analyses revealed that both compounds interacted favorably with CRMP-2
      while crucial residues that enhanced their selective binding include Glu353,
      Thr349, Lys254, Asp140 and Arg75. These structural insights provide mechanistic
      events that could contribute towards the structure-based design of anti-AD
      molecules which can bind CRMP2 selectively and alter its phosphorylation process.

PMID- 30290063
TI  - The Brain and Inner Ear of the Early Paleocene "Condylarth" Carsioptychus
      coarctatus: Implications for Early Placental Mammal Neurosensory Biology and
      Behavior.
AB  - Mammals underwent a profound diversification after the end-Cretaceous mass
      extinction, with placentals rapidly expanding in body size and diversity to fill
      new niches vacated by dinosaurs. Little is known, however, about the brains and
      senses of these earliest placentals, and how neurosensory features may have
      promoted their survival and diversification. We here use computed tomography (CT)
      to describe the brain, inner ear, sinuses, and endocranial nerves and vessels of
      Carsioptychus coarctatus, a periptychid "condylarth" that was among the first
      placentals to blossom during the few million years after the extinction, in the
      Paleocene. Carsioptychus has a generally primitive brain and inner ear that is
      similar to the inferred ancestral eutherian/placental condition. Notable
      "primitive" features include the large, anteriorly expanded, and conjoined
      olfactory bulbs, proportionally small neocortex, lissencephalic cerebrum, and
      large hindbrain compared to the cerebrum. An encephalization quotient (EQ) cannot
      be confidently calculated because of specimen crushing but was likely very small,
      and comparisons with other extinct placentals reveal that many Paleocene
      "archaic" mammals had EQ values below the hallmark threshold of modern placentals
      but within the zone of nonmammalian cynodonts, indicative of small brains and low
      intelligence. Carsioptychus did, however, have a "conventional" hearing range for
      a placental, but was not particularly agile, with semicircular canal dimensions
      similar to modern pigs. This information fleshes out the biology of a keystone
      Paleocene "archaic" placental, but more comparative work is needed to test
      hypotheses of how neurosensory evolution was related to the placental radiation.
      Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30290064
TI  - Long noncoding RNA FAL1 promotes proliferation and inhibits apoptosis of human
      colon cancer cells.
AB  - Aberrant expression of long non-coding RNAs (lncRNAs) has been associated with a
      variety of malignancies including colon cancer. In this study, we aimed to
      characterize the biological mechanisms of focally amplified lncRNA on chromosome
      1 (FAL1) in colon cancers. Here, our results indicate that FAL1 expression was
      remarkably up-regulated in colon tumor tissues as compared to corresponding tumor
      adjacent normal tissues. Importantly, the cumulative survival rate of patients
      with high levels of FAL1 in tumor tissues was considerably lower than those with
      low FAL1 levels in tumor tissues. Cox regression analysis showed that lncRNA FAL1
      could act as an independent prognostic factor in CRC. Knockdown of FAL1 in HT29
      cells attenuated cell proliferation and stimulated cell apoptosis. In contrast,
      overmetastasis-related molecules Bcl-2, TGF-beta1, p65, and PCNA at the mRNA and
      protein levels. Mechanistically, FAL1 was found to interact with STAT3 at 200 to
      400 bp and promote phosphorylation of STAT3. In addition, we found that knockdown
      of STAT3 in HT29 cells abolished the effects of FAL1 on cell proliferation as
      well as the expression of TGF-beta1 and Bcl-2. Based on these findings, we
      concluded that FAL1 might be a potential oncogene for the progression of colon
      cancer. (c) 2018 IUBMB Life, 70(11):1093-1100, 2018.

PMID- 30290065
TI  - Postpartum depression and child growth in Tanzania: a cohort study.
AB  - OBJECTIVE: To examine the association between postpartum depression and child
      growth in a Tanzanian birth cohort. DESIGN: Prospective cohort study. SETTING:
      Moshi, Tanzania. POPULATION: Pregnant women over the age of 18 who sought
      antenatal care at two health clinics in Moshi, and the children they were
      pregnant with, were assessed for inclusion in this study. METHODS: The women were
      interviewed twice during pregnancy and three times after birth, the final follow
      up taking place 2-3 years postpartum. Signs of postpartum depression were
      assessed approximately 40 days postpartum with the Edinburgh Postnatal Depression
      Scale. MAIN OUTCOME MEASURES: Child growth was assessed with anthropometric
      measurements at 2-3 years of age and expressed as mean z-scores. RESULTS: In all,
      1128 mother-child pairs were followed throughout the duration of the study. In
      total, 12.2% of the mothers showed signs of postpartum depression. Adjusted mean
      height-for-age z-score (HAZ) was significantly lower at 2-3 years follow up for
      children of mothers with postpartum depression than for children of mothers
      without (difference in HAZ: -0.32, 95% CI-0.49 to -0.15). Adjusted mean weight
      for-height z-score (WHZ) was significantly increased for the children exposed to
      postpartum depression (difference in WHZ: 0.21, 95% CI 0.02-0.40), whereas there
      was no significant difference in adjusted weight-for-age z-score (WAZ; difference
      in WAZ: -0.04, 95% CI -0.20 to 0.12). CONCLUSIONS: We found that postpartum
      depressive symptoms predicted decreased linear height in children at 2-3 years of
      age and slightly increased weight-for-height. TWEETABLE ABSTRACT: Postpartum
      depression in Tanzanian mothers is associated with impaired child growth at 2-3
      years of age.

PMID- 30290066
TI  - Thymoquinone attenuates lead-induced nephropathy in rats.
AB  - Kidney hazards from lead (Pb) exposure are one of the fastest growing areas of
      concern in toxicology today. The thymoquinone (TQ) renoprotective effect against
      Pb-induced nephropathy has not previously been studied. Therefore, adult male
      Wistar rats were treated with Pb (2000 ppm of Pb acetate in drinking water)
      and/or TQ (5 mg/kg/day,  per os). All treatments were applied for 5 weeks. The
      results indicated that Pb exposure produced metal deposition, histopathological
      changes, functional impairment (significant elevation in plasma urea, uric acid,
      and creatinine levels), total antioxidant status decrease, and lipid peroxidation
      stimulation in the kidneys. Interestingly, TQ supplementation remarkably improved
      the Pb-induced renal adverse effects without significantly reducing the tissue
      metal accumulation. In conclusion, our data indicate for the first time a
      protective effect of TQ against Pb-induced nephropathy, most likely through an
      antioxidant mechanism. On this basis, TQ deserves more consideration and further
      examination as a potential therapeutic option.

PMID- 30290067
TI  - Being underweight in adolescence is independently associated with adult-onset
      diabetes among women: The Japan Nurses' Health Study.
AB  - AIMS/INTRODUCTION: To examine the association between adult-onset diabetes and
      life-course bodyweight changes. MATERIALS AND METHODS: In a cross-sectional
      study, 17,398 Japanese female nurses aged >=30 years completed a self
      administered questionnaire in 2001-2007. Bodyweight indices were calculated for
      three life stages: birthweight (adjusted for gestational age), body mass index
      (BMI) at age 18 years and current BMI. Odds ratios for being diagnosed with adult
      onset diabetes were calculated according to the combined bodyweight categories of
      two life stages: at birth and age 18 years; and at age 18 years and the survey
      (current). Path analysis was carried out to decompose the effect of each
      bodyweight index into direct and mediating effects. RESULTS: After adjustment for
      age at survey and parental diabetes history, "low" birthweight (<25th
      percentile), when combined with either "low" or "high" BMI (>=75th percentile) at
      age 18 years, had significant odds ratios (2.32, 95% confidence interval [CI]
      1.22-4.44; 3.69, 95% CI 2.12-6.42, respectively) compared with the group of
      "middle" category (25th-74th percentile) at both life stages. The combination of
      "low" BMI at age 18 years and "high" current BMIs showed the highest odds ratio
      (7.97, 95% CI 3.97-16.00). Among women without parental diabetes history, "low"
      BMI at age 18 years showed a significantly high odds ratio (2.25, 95% CI 1.01
      4.99), even when combined with the "middle" category of current BMI. Path
      analysis showed that both birthweight and BMI at age 18 years had a negative
      direct effect on adult-onset diabetes. CONCLUSIONS: Underweight at adolescence,
      as well as overweight, is a potential risk factor for adult-onset diabetes among
      Japanese women.

PMID- 30290068
TI  - Australian European Self-Assembly through Macromolecular Interactions II.

PMID- 30290069
TI  - Fat cell lipolysis and future weight gain.

PMID- 30290070
TI  - Human glomerular transcriptome of diabetic kidneys: Can the podocyte cytoskeleton
      be a therapeutic target?

PMID- 30290071
TI  - Finite-Element Syntheses of Callus and Bone Remodeling: Biomechanical Study of
      Fracture Healing in Long Bones.
AB  - Computational simulations of fracture healing are a valuable tool to improve
      fracture treatment and implants. Several finite-element models have been
      established to predict callus formation due to mechanobiological rules. This work
      provides a comprehensive simulation for virtual implantation through the
      combination of callus simulation and finite-element structural synthesis (FESS)
      of (re-)modeling during and after healing based on Pauwel's theory of
      histogenesis and Wolff's law. The simulation is based on a linear elastic
      material model and includes generation of fracture hematoma and initial
      mesenchymal stem cell concentration out of an unspecified solid, cell
      proliferation, migration, and differentiation due to mechanical stimuli and time
      dependent axial loading. Three nondisplaced femoral shaft fractures with initial
      interfragmentary movement of 0.2, 0.6, and 1 mm and one fracture with 4 mm
      translation are modeled. The predictions of interfragmentary movement during
      fracture healing, healing success, and healing time agree with observed clinical
      outcome, animal models, and other numerical models. Initial interfragmentary
      movement between 0.2 and 1 mm leads to healing success, with the fastest healing
      occurring at 0.2 mm. The model of the dislocated fractures shows no further
      bending after remodeling and is loaded with physiological stress of -13 MPa.
      Ideal load-time graphs may give insight into the bone's ability to withstand
      loads as healing time progresses, and thus holds potential for applications in
      rehabilitation planning. Better knowledge of the forces present during fracture
      healing is needed to deploy simulations for surgical planning and manufacturing
      of patient individualized implants. Anat Rec, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 30290072
TI  - Cell culture media for recombinant protein expression in Chinese hamster ovary
      (CHO) cells: History, key components, and optimization strategies.
AB  - The culture of Chinese Hamster Ovary (CHO) cells for modern industrial
      applications, such as expression of recombinant proteins, requires media that
      support growth and production. Such media must support high viable cell densities
      while also stimulating the synthesis and extracellular transport of biologic
      products. Early media development efforts in this area yielded basic formulations
      to sustain growth, viability, and cellular function, albeit comprising animal
      sourced components, and complex constituents used in batch culture mode.
      Subsequent improvements included the development of serum-free and chemically
      defined (CD) media, the identification of critical nutrients, growth factors, and
      potentially inhibitory or toxic cellular metabolites, and the use of fed-batch
      and perfusion culture techniques to optimize nutrient delivery while minimizing
      accumulation of unwanted waste products. This review is comprised of sections
      covering milestones in the evolution of mammalian cell culture media, nutrient
      composition and formulation requirements, optimization strategies, consistency
      and scalability of powder and liquid media preparation for industrial
      applications, and key recent advances driving progress in CHO cell culture medium
      design and development. (c) 2018 American Institute of Chemical Engineers
      Biotechnol. Prog., 2018.

PMID- 30290073
TI  - Developmental Morphology of the Palatine Glands in Rats: An Electron Microscope
      Study.
AB  - Although minor salivary glands play a significant functional role in the oral
      cavity, their developmental morphology and cell differentiation has been scarcely
      studied. This study aimed to describe the development of rat palatine glands with
      regard to the ultrastructural morphology of the secretory cells and surrounding
      myoepithelial cells (MECs). Palatine glands from rats at embryonic ages (E) 18
      and 20 days, and postnatal days (PN) 0, 3, 7, 10, 13, 21, 30, 42, and 60 were
      fixed and prepared for morphological analysis and immunocytochemical labeling of
      alpha-smooth muscle actin (alpha-SMA). At E18, epithelial cords were observed
      extending from the palatal epithelium and showed negative reactivity to alpha
      SMA. After luminization at E20, the cells of immature acini accumulated secretory
      granules of various densities: electron-dense, electron-lucent and some empty
      appearing granules. MECs were poorly differentiated at E20 and exhibited only
      slight alpha-SMA expression. At birth, mucous and serous cells were typically
      located around a common lumen. Thereafter, serous cells began to move to the
      periphery to form demilunes by PN7. The mucous secretory granules of intermediate
      electron density became predominant around PN13. At PN21, these granules were
      dramatically reduced in number and most of the acini in adults contained acinar
      cells with numerous electron-lucent granules, and a few serous demilune cells
      with electron-dense granules. After birth, MECs progressively accumulated actin
      microfilaments until prominent alpha-SMA expressing MECs invested the acini and
      the proximal part of the intercalated ducts in the adult. Anat Rec, 301:1820
      1833, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30290074
TI  - Restoration of myocardial glucose uptake with facilitated myocardial glucose
      transporter 4 translocation contributes to alleviation of diabetic cardiomyopathy
      in rats after duodenal-jejunal bypass.
AB  - AIMS/INTRODUCTION: Duodenal-jejunal bypass (DJB) surgery has been reported to
      effectively relieve diabetic cardiomyopathy (DCM). However, the specific
      mechanisms remain largely unknown. The present study was designed to determine
      the alterations of myocardial glucose uptake (MGU) after DJB and their effects on
      DCM. MATERIALS AND METHODS: Duodenal-jejunal bypass and sham surgeries were
      carried out in diabetic rats induced by a high-fat diet and a low dose of
      streptozotocin, with chow-diet fed rats as controls. Bodyweight, food intake,
      glucose homeostasis and lipid profiles were measured at indicated time-points.
      Cardiac function was evaluated by transthoracic echocardiography and hemodynamic
      measurement. Cardiac remodeling was assessed by a series of morphometric analyses
      along with transmission electron microscopy. Positron-emission tomography with
      fluorine-18 labeled fluorodeoxyglucose was carried out to evaluate the MGU in
      vivo. Furthermore, myocardial glucose transporters (GLUT; GLUT1 and GLUT4),
      myocardial insulin signaling and GLUT-4 translocation-related proteins were
      investigated to elucidate the underlying mechanisms. RESULTS: The DJB group
      showed restored systolic and diastolic cardiac function, along with significant
      remission in cardiac hypertrophy, cardiac fibrosis, lipid deposit and
      ultrastructural disorder independent of weight loss compared with the sham group.
      Furthermore, the DJB group showed upregulated myocardial insulin signaling,
      hyperphosphorylation of AKT substrate of 160 kDa (AS160) and TBC1D1, along with
      preserved soluble N-ethylmaleimide-sensitive factor attachment protein receptor
      proteins, facilitating the GLUT-4 translocation to the myocardial cell surface
      and restoration of MGU. CONCLUSIONS: The present findings provide evidence that
      restoration of MGU is implicated in the alleviation of DCM after DJB through
      facilitating GLUT-4 translocation, suggesting a potential choice for treatment of
      human DCM if properly implemented.

PMID- 30290075
TI  - Combating Excessive Eating: A Role for Four Evidence-Based Remedies.
AB  - OBJECTIVE: The aim of this study is to review the control of energy balance and
      outline some causes of and remedies for excessive energy intake. METHODS: A
      narrative review was conducted. RESULTS: There is negative feedback control of
      energy intake and body weight, but, nonetheless, energy intake is only loosely
      coupled with energy expenditure. Consequently, we are vulnerable to eating in
      excess of energy requirements. In this context, energy density, portion size, and
      habitual meal patterns have strong influences on energy intake and, accordingly,
      can be targeted to reduce energy intake. For example, energy density can be
      reduced without much affecting food reward (approximately the pleasure gained
      from eating) because their relationship is such that reward value is affected
      relatively little by increments in energy density above 1.5 kcal/g. This and
      other strategies that increase reward per calorie eaten may be superior to
      increasing the satiety effect of products because fullness is not inherently
      rewarding. Low-calorie sweeteners provide a means to reduce energy density while
      largely preserving food or beverage reward value. Consistent with this,
      consumption of low-calorie sweeteners compared with consumption of sugars has
      been found to reduce energy intake and body weight. CONCLUSIONS: Understanding
      what causes excessive eating also provides insights into how to combat this
      problem.

PMID- 30290076
TI  - Low-Calorie Sweeteners: Exploring Underutilized Database Resources to Understand
      Dietary Patterns and Obesity.
AB  - The use and impact of low-calorie sweeteners (LCS) in relation to the national
      challenges of overweight and obesity are complex and controversial. Most research
      on LCS have focused on the prevalence of consumption of LCS in beverages. The
      2015 Dietary Guidelines Advisory Committee emphasized dietary patterns and health
      rather than a focus on specific nutrients or foods. The committee took this
      approach to shift the national emphasis onto the context of total rather than
      individual nutrient consumption. A broader research paradigm is needed to
      elucidate the actual exposure to LCS and how they are consumed within dietary
      patterns in the US population. National-level databases exist that can be used to
      broaden scientific understanding of the effects of LCS and health outcomes. These
      databases are underutilized, and they provide potential tools for grasping a
      fuller picture of LCS in the US diet.

PMID- 30290077
TI  - Oral Post-Oral Actions of Low-Calorie Sweeteners: A Tale of Contradictions and
      Controversies.
AB  - OBJECTIVE: Many scientists and laypeople alike have concerns about low-calorie
      sweeteners (LCSs). These concerns stem from both a dissatisfaction with the taste
      of LCSs and reports that they cause metabolic disruptions (e.g., weight gain,
      glucose intolerance). METHODS: This article provides a critical review of the
      literature on LCSs from the standpoint of their taste, gastrointestinal, and
      metabolic effects; biological fate in the body; and impact on ingestion and
      glucose homeostasis. RESULTS AND CONCLUSIONS: Mammals can readily discriminate
      between LCSs and sugars because both types of sweetener activate distinct oral
      and post-oral sensory pathways. LCSs differ in their ability to access post-oral
      tissues, but few studies have incorporated this observation into their design. It
      is difficult to extrapolate results between mice, rats, and humans because of
      interspecies differences in the taste and post-oral actions of LCSs and the fact
      that investigators often use different response measures in rodents and humans.
      There is confounding in the experimental design of some of the most widely cited
      studies of LCS-induced metabolic disruptions. The uncritical acceptance of these
      studies has generated considerable controversy. More work is needed to obtain a
      clearer understanding of the metabolic effects of LCSs.

PMID- 30290078
TI  - Low-Calorie Sweeteners and Weight Management: What Does the Future Hold?

PMID- 30290079
TI  - Contribution of pancreatic alpha-cell function to insulin sensitivity and
      glycemic variability in patients with type 1 diabetes.
AB  - AIMS/INTRODUCTION: To evaluate the contribution of pancreatic alpha-cell function
      to the dawn phenomenon, insulin sensitivity, hepatic glucose uptake and glycemic
      variability in patients with type 1 diabetes. MATERIALS AND METHODS: In 40
      patients with type 1 diabetes, arginine stimulation tests were carried out, and
      the area under the curve (AUC) of glucagon was measured using radioimmunoassays
      (AUCglc RIA ) and enzyme-linked immunosorbent assays (AUCglc ELISA ). The ratio
      of the insulin dose delivered by an artificial pancreas to maintain euglycemia
      between 04.00 and 08.00 hours or between 00.00 and 04.00 hours was measured as
      the dawn index. The glucose infusion rate and hepatic glucose uptake were
      measured using hyperinsulinemic euglycemic clamp and clamp oral glucose loading
      tests. Glycemic variability in 96 h was measured by continuous glucose
      monitoring. RESULTS: The median dawn index (1.7, interquartile range 1.0-2.8) was
      not correlated with AUCglc RIA (R2  = 0.03, P = 0.39) or AUCglc ELISA (R2  =
      0.04, P = 0.32). The median glucose infusion rate (7.3 mg/kg/min, interquartile
      range 6.4-9.2 mg/kg/min) was significantly correlated with AUCglc RIA (R2  =
      0.20, P = 0.02) and AUCglc ELISA (R2  = 0.21, P = 0.02). The median hepatic
      glucose uptake (65.3%, interquartile range 40.0-87.3%) was not correlated with
      AUCglc RIA (R2  = 0.07, P = 0.26) or AUCglc ELISA (R2  = 0.26, P = 0.79). The
      standard deviation of glucose levels measured by continuous glucose monitoring
      was significantly correlated with AUCglc RIA (R2  = 0.11, P = 0.049), but not
      with AUCglc ELISA (R2  = 0.01, P = 0.75). CONCLUSIONS: Pancreatic alpha-cell
      function contributed to insulin sensitivity in patients with type 1 diabetes.

PMID- 30290080
TI  - Explaining the Different Geometries of the Water Oxidising Complex in the Nominal
      S3 State Crystal Structures of Photosystem II at 2.25 A and 2.35 A.
AB  - Recently two atomic resolution crystal structures of Photosystem II, in the
      double flashed, nominal S3 intermediate state of its Mn4 Ca water oxidising
      complex (WOC), have been presented (Young et al., Nature 2016, 540, 453; Suga et
      al., Nature 2017, 543, 131). These structures are at 2.25 A and 2.35 A
      resolution, respectively. Although highly similar in most respects, the
      structures differ in a key region within the WOC catalytic site. In the 2.25 A
      structure, one oxy species (O5) is observed within the WOC cavity, weakly
      associated with the Mn centres, similar to that seen earlier in the 1.95 A XRD
      structure of the S1 intermediate (Suga et al., Nature, 2015, 517, 99). In the
      2.35 A structure, two such species are seen (O5, O6), with the Mn centres and O5
      positioned as in the 2.25 A structure and an O5-O6 separation of ~1.5 A,
      consistent with peroxo formation. This suggests O5 and O6 are substrate water
      derived species in this double flashed form. Recently we have presented (Petrie,
      et al., Chem. Phys. Chem., 2017) a large scale (220 atom) quantum chemical model
      of the Young et al. 2.25 A structure, which quantitatively explains all
      significant features within the WOC region of that structure, particularly the
      positions of the metal centres and O5 group. Critical to this was our assumption
      of a 'low' Mn oxidation paradigm (mean S1 Mn oxidation level of +3.0, Petrie et
      al., Angew. Chem. Int. Ed., 2015), rather than a 'high' oxidation model (mean S1
      oxidation level of +3.5), widely assumed in the literature. Here we show that our
      same oxidation state model predicts two classes of energetically close S3
      structural forms, analogous to the S1 state, one with the metal centres and O5
      positioned as in the 2.25 A structure, and the other with the metals similarly
      placed, but with O5 located in the O6 position of the 2.35 A structure. We show
      that the Suga et al. 2.35 A structure is likely a superposition of two such
      forms, one from each class, which is consistent with reported atomic occupancies
      for that structure and the relative total energies we calculate for the two
      structural forms.

PMID- 30290081
TI  - Redesign of a New Manganese Peroxidase Highly Expressed in Pichia pastoris
      towards a Lignin-Degrading Versatile Peroxidase.
AB  - Manganese peroxidases, lignin peroxidases, and versatile peroxidases secreted by
      white rot fungi are supposed to play an essential role in lignin degradation.
      Thus, these enzymes have attracted significant attention as potential
      biocatalysts. Versatile peroxidases are the most interesting ones, since they
      comprise activities of manganese and lignin peroxidases. Herein, we demonstrate
      how the properties of a new manganese peroxidase from Moniliophthora roreri,
      designated MrMnP1, were shifted towards those of a versatile peroxidase. MrMnP1
      was cloned in Pichia pastoris X-33 and highly expressed in a fed-batch
      fermentation, yielding 132 mg L-1 of active enzyme. To extend the substrate
      spectrum of MrMnP1, a catalytically active tryptophan present in lignin and
      versatile peroxidases was first introduced. Additionally, the role of five amino
      acids at positions adjacent to the catalytic tryptophan was elucidated through
      their replacement by those found in a versatile peroxidase from Pleurotus
      eryngii. The resulting mutants demonstrated new activities towards high-redox
      potential substrates, such as lignin dimers, veratryl alcohol, and the azo dye
      Reactive Black 5.

PMID- 30290082
TI  - Autophagy Induction Plays Time-Dependent Role in Viral Load of HCV Infected
      Huh7.5 Cell Line.
AB  - Autophagy provides an initial membranous platform for incoming hepatitis C virus
      (HCV) RNA translation and immune evasion. Once HCV replication is established,
      this infrastructure will be unnecessary for translation of HCV RNA progeny. So,
      the autophagy plays key role in the replication and immune pathogenesis of HCV
      virus. The aim of this study was to study the effect of autophagy induction in
      Huh7.5 cell on virus titer. The Huh7.5 cell was transfected with recombinant
      pcDNA-Beclin1. The autophagy induction was evaluated via microtubule associated
      protein 1 light chain 3 staining as autophagy formation marker using flow
      cytometry. The HCV (JFH1) was inoculated 12-h post-transfection. Next, to
      evaluate the viral load, viral RNA was extracted after 24 and 48 h and virus
      titer was calculated using real-time PCR. The result of the current study shows
      that the induction of autophagy before virus infection was able to enhance virus
      yield from 4 * 103 copies/mL to 1 * 104 copies/mL at 24-h post-infection, but
      reduced viral load after 48 h up to 6 * 103 copies/mL. The study of cross-talk
      between autophagy and HCV may bring new hope for human intervention and treatment
      of HCV. Also, it opens new avenue to improve virus cultivation in cell culture
      and understanding HCV and host cell responses. (c) 2018 IUBMB Life, 2018.

PMID- 30290083
TI  - The Embryonic Ascent of the Kidney Revisited.
AB  - Although the embryonic kidney's ascent is well established, the intermediate
      morphological changes that occur during the process are unclear. To evaluate the
      morphological events that accompany the kidney's ascent, we examined serial
      sagittal sections from 24 embryos at 5-7 weeks gestation. Six specimens had
      bilaterally ascending kidneys that were between the levels of the second to fifth
      lumbar vertebrae, and each kidney had a primitive renal cortex surrounding
      clusters of ampullae, which branched from the pelvis, and a dense tissue band
      that connected the renal cortex with the embryonic adrenal cortex or celiac
      ganglia, and there was no adipose capsule or renal artery. The tissue band
      contained abundant nerve twigs from the major splanchnic nerve; thus, it was
      conceivable that it was sufficiently rigid to support the length of the
      retroperitoneal tissue mass that included the embryonic adrenal cortex, celiac
      ganglia, and kidney. The lumbar vertebral body's height was much shorter than
      that of the ascending kidney. However, the lower vertebral column's curvature was
      often maintained, even when the kidneys had ascended. Therefore, vertebral column
      straightening was not the only factor required to drive the ascent. Together with
      the growth of the thorax and liver, the adrenal cortex, ganglia, and kidney
      appeared to change simultaneously at a position relative to the vertebrae. The
      renal artery established a connection to the renal cortex after the ascent.
      Evaluations of frontal sections from five additional specimens suggested that
      from its initial position, the kidney extended upwards between bilateral
      umbilical arteries. Anat Rec, 2018. (c) 2018 The Authors. The Anatomical Record:
      Advances in Integrative Anatomy and Evolutionary Biology published by Wiley
      Periodicals, Inc. on behalf of Wiley-Liss, Inc.

PMID- 30290084
TI  - High-Fat Diet, Betaine, and Polydextrose Induce Changes in Adipose Tissue
      Inflammation and Metabolism in C57BL/6J Mice.
AB  - SCOPE: High-fat diets are a likely cause of low-grade inflammation and obesity
      related pathologies. This study measures the effects of a high-fat diet, in
      combination with two dietary supplements-betaine and polydextrose-on metabolism
      and inflammation in the adipose tissue of diet-induced obese mice. METHODS AND
      RESULTS: Forty male C57BL/6J mice are fed a high-fat diet for 8 weeks and
      compared with low-fat-diet-fed control animals (n = 10). For the last 4 weeks,
      the high-fat-diet-fed animals are supplemented with 1% betaine, 3.33%
      polydextrose, their combination, or plain water. Fat depots from subcutaneous and
      visceral adipose tissue are analyzed for inflammatory markers and nontargeted
      metabolomics by quantitative PCR and LC-QTOF-MS. The high-fat diet significantly
      increases adipose tissue inflammation in both fat depots. By metabolic profiling,
      clear differences are noted between low-fat-diet and high-fat-diet groups with
      regard to the levels of several metabolite species-primarily carnitines, lipids,
      and amino acids. Dietary betaine mitigates the high-fat-diet-induced IL-6
      expression and significantly increases betaine and butyrobetaine levels in
      adipose tissue. CONCLUSIONS: The high-fat diet induces patent changes in
      carnitine and lipid metabolism in adipose tissue. Betaine supplementation
      elevates the levels of betaine and its derivatives and certain carnitine species,
      as reported in muscle and liver, and moderately reduces inflammation.

PMID- 30290085
TI  - Hidden myelodysplastic syndrome (MDS): A prospective study to confirm or exclude
      MDS in patients with anemia of uncertain etiology.
AB  - INTRODUCTION: Diagnosis of myelodysplastic syndromes (MDSs) when anemia is the
      only abnormality can be complicated. The aim of our study was to investigate the
      primary causes of anemia and/or macrocytosis of uncertain etiology. METHODS: We
      conducted a multicenter, prospective study over 4 months in three hematology
      laboratories. In step 1, we used an automated informatics system to screen 137
      453 hemograms for cases of anemia and/or macrocytosis (n = 2702). In step 2, we
      excluded all patients whose anemia appeared to be due to a known cause. This left
      290 patients had anemia of uncertain etiology. In step 3, we conducted further
      investigations, including a peripheral blood smear, and analysis of iron, vitamin
      B12, folate, and thyroid hormone levels. RESULTS: A differential diagnosis was
      obtained in 139 patients (48%). The primary causes of anemia were iron deficiency
      (n = 59) and megaloblastic anemia (n = 39). In total, 25 hematologic disorders
      were diagnosed, including 14 patients with MDS (56%). The median age of MDS
      patients was 80 years, 12 had anemia as an isolated cytopenia, and most (n = 10)
      had lower-risk disease (IPSS-R <= 3.5). SF3B1 mutations were most frequent (n =
      6) and correlated with the presence of ring sideroblasts (100%) and associated
      with better prognosis (P = 0.001). CONCLUSIONS: Our prospective, four-step
      approach is an efficient and logical strategy to facilitate the diagnosis of MDS
      on the basis of unexplained anemia and/or macrocytosis, and may allow the early
      diagnosis of the most serious causes of anemia. Molecular analysis of genes
      related to MDS could be a promising diagnostic and prognostic approach.

PMID- 30290086
TI  - Results of Questionnaire Survey on Gross Anatomy Education (March 2014).
AB  - To understand the current situation of gross anatomy education anatomy classes.
      Regarding the influence of increased enrollment and to promote sharing of
      information on its improvement, we capacity in medical schools, many respondents
      were worried about conducted a questionnaire survey on gross anatomy education
      the impact on research activities due to the increase in teaching in September
      2013. In most medical and dental schools, gross workload without expanding in
      teaching staff. In some schools, anatomy courses were offered to second-year
      students. The owing to the limitations of the facilities or the number of donated
      average numbers of gross anatomy practices were 34.6 in medical bodies, the
      number of students per cadaver had to be increased. schools and 27.4 in dental
      schools. The average total hours of We received various effective and practical
      measures for the practice in the curriculum was 125 in medical schools, and 97
      improvement of gross anatomy education, such as improvement in dental schools.
      However, in about 80% of total schools, the of teaching materials and dissection
      methods, introduction of length of the actual gross anatomy practice was
      considerably lectures on clinical anatomy by clinicians, and implementation
      longer, because the students could not finish the work within of the second-round
      gross anatomy practice in the upper grades. the allotted class time. As to the
      effect of curriculum reform in Many respondents emphasized both the need for a
      training system respond to the introduction of the accreditation of medical and
      for young teaching staff, and the importance of opportunities for dental
      education programs, many respondents answered that sharing information on
      education. they had a minimal effect except earlier commencement of gross.

PMID- 30290087
TI  - Itchy Lip-Swollen Tongue Swollen Lip It's not Always an Allergy to Dental
      Materials; Angioederna- Possibly Life Threatening! You Might See This in Your
      Practice.
AB  - When providing dental treatment, the dental clinician (DC) is expected to be
      knowledgeable in recognition and emergency management of an allergic response.
      Common manifestations of localized allergic responses can present as a rash or
      hives (urticaria), running of the nose, and swelling of the lips, eyes, face,
      respiratory and gastrointestinal mucosa. More critically, there is the potential
      for breathing difficulties from laryngeal swelling. Airway obstruction can be
      potentially life threatening.' Anaphylactic shock can be another serious
      reaction. Although most of these allergic responses can be minimal and managed
      with an antihistamine (diphenhydramine), more serious allergic reactions (marked
      breathing difficulty, anaphylaxis) may require the use of an intramuscular
      injection of epinephrine. This case report describes a patient who had what
      appeared to be a common allergic response to some aspect of dental materials or
      treatment but was subsequently diagnosed with an allergic condition known as
      angioedema (AE) that had the potential to be non-responsive to dental office
      emergency medications. AE may be due to the more common histamine generated
      process as described below. However, if the patient's AE is due to alternate
      pathophysiology, the DC may not be able to manage breathing difficulties due to
      airway swelling, which could be rapidly fatal.

PMID- 30290088
TI  - What's My Diagnosis? A Case Study Submitted by:.

PMID- 30290089
TI  - Dental Economics and the Increasing Numbers of Individuals with Disabilities in
      New Jersey.
AB  - The dual needs of 1) providing increasing oral healthcare for individuals with
      special needs, and 2) improving the economics of dental practice, are explored in
      a review of the State of New Jersey and its counties.

PMID- 30290090
TI  - A Team Approach to Restoration of the Extremely Worn Dentition: A Clinical
      Report.

PMID- 30290091
TI  - What is Missing for Stem Cell-Based Therapies in Dentistry.
AB  - There have been significant advancements in regenerative dentistry demonstrated
      in large animal studies, particularly in the areas of endodontics and
      periodontics. By using dental stem cells, pulp tissues can be regenerated in
      empty root canal space, and periodontal pockets can be regenerated to its normal
      state. To further test its clinical applications and perhaps to provide such
      patient care service if proven safe and successful, a facility called good
      manufacturing practice where stem cells are processed is needed. However, such
      facilities are rare.

PMID- 30290092
TI  - Antibiotic Therapy in the Treatment of Odontogenic Infections-An Evolving
      Landscape.
AB  - Odontogenic infections continue to be the most common reason for people to seek
      dental care. Antibiotic therapy, combined with appropriate surgical intervention
      has been the mainstay in treating dental infections for many years. Availability
      of new antimicrobial agents and reports of decreased efficacy in commonly used
      antibiotics warrant continued study to assure that the most effective agents are
      utilized. This paper presents a brief summary of the bacterial populations
      associated with odontogenic infection and their antibiotic resistance mechanisms.
      Information from a number of studies, including our own data, concerning
      antibiotic resistance and efficacy are presented. This paper may provide the
      practitioner with additional information as a guide for appropriate antibiotic
      use in odontogenic infections.

PMID- 30290093
TI  - Comparison of Laser Versus Rotary Instrumentation- A Case Study.
AB  - The use of an erbium laser to treat carious teeth has proven to have several
      advantages when compared to rotary instruments. The clinician is able to remove a
      minimal amount of tooth structure, thus minimizing the risk of pulpal exposure.
      The extremely short pulses of erbium lasers combined with an aerosolized water
      spray have been shown to cool the pulp as opposed to rotary instruments which may
      create heat that could lead to a pulpitis. Bonding to the lased surfaces is
      improved because the smear layer is removed, bleeding is controlled, and the
      lased tooth surface appears etched with open dentinal tubules. The laser also
      provides a bactericidal effect and the need for local anesthetics is eliminated
      or reduced. The use of the erbium laser to prepare cavity preparations can be
      done as quickly, or oftentimes more quickly, than using a rotary instruments. In
      addition, patients appreciate the absence of the high speed drill noise and
      vibration.

PMID- 30290094
TI  - We May Have Done Something Right: Composite Restorations at the College of
      Dentistry, University of Tennessee Health Science Center.
AB  - The success of composite restorations requires meticulous clinical technique in
      addition to reliable restorative materials and armamentarium. Early failure of
      restorations is undesirable and are usually replaced at no cost to patients. A
      metaanalysis study reported a mean annual failure rate of 1.46% for posterior
      composite restorations. At the University of Tennessee Health Science Center
      College of Dentistry (UTHSC CoD) predoctoral clinic the percentage of posterior
      composite restorations replaced within 12 months, retrieved from 2007-2014
      electronic chart 'redo' records, was on average 0.58%. Several factors may have
      contributed to the quality of composite restorations placed by novice clinicians
      with modest experience. Student doctors are educated about composite placement in
      preclinical courses and then work under close supervision during their clinical
      training. This article describes restorative techniques for composites and the
      rationales taught at the UTHSC CoD Department of Restorative Dentistry. The
      objective is to share the information, which can be adopted or modified by
      general practitioners in daily practice.

PMID- 30290095
TI  - Provisional Replacement of Anterior Teeth: A Review of Clinical Techniques and
      Case Report in a Dental School Training Experience.
AB  - Upon the premature loss of permanent anterior teeth from unanticipated trauma or
      by ongoing patient neglect requiring surgery, patient requisites of functional
      and esthetic considerations must be addressed. Interim management can be achieved
      through the use of several diverse fixed and/or removable treatment modalities.
      The purposes of this report are to provide a review of traditional and
      unconventional techniques for interim replacement of missing anterior teeth and
      to present a clinical report demonstrating the fabrication of a removable,
      thermoplastic (vacuum-formed) EssixTM prosthesis, utilizing composite resin as
      the surrogate material of choice for the absent teeth. This measure proved to be
      an immediate, esthetic, and transitional treatment solution prior to a permanent
      resolution for the patient's long-term dental requirements.

PMID- 30290096
TI  - Tennessee Dental Establishments: 2007-2012 Economic Survey.
AB  - OBJECTIVE: To document the evolving economies of dental establishments in the
      State of Tennessee during a period of significant growth of the number of
      establishments before and after the "Great Recession." METHOD: Published results
      from the five-year economic surveys by the U.S. Census Bureau on business
      receipts and salaries of employees (including dentists) for the State of
      Tennessee and its counties were used to construct a review of these developments.
      RESULTS: Between 2007 and 2012, there were continued increases in average current
      dollar business receipts and employee salaries. However, in terms of standard
      dollars, removing the effects of inflation: 1) business receipts increased in 19
      counties but decreased in 37 counties; 2) employee salaries increased in 13
      counties but decreased in 30 counties. CONCLUSIONS: Results are in line with the
      reports by the ADA Health Policy Institute, which indicate that nationally the
      percentage of dentists who report they are not busy enough has increased and
      dentists' earnings are stagnating. The need is to expand the delivery of care to
      underserved populations, including the poor, individuals with disabilities,
      minorities and new immigrant populations, for whom oral health services may not
      be a priority commodity.

PMID- 30290097
TI  - A Novel Protocol to Evaluate Hard and Soft Tissue Relationships in Three
      Dimensions without the Use of Additional Radiographic Studies.
AB  - OBJECTIVE: The evaluation of hard and soft tissue relationships is an important
      part of the study of facial morphology, craniofacial development and orthodontic
      treatment and outcomes. Historically, this evaluation has occurred in two
      dimensions. The purpose of this study was to develop a protocol to study the
      relationships of hard and soft tissues in three dimensions without the use of
      additional radiation. MATERIALS AND METHODS: Stereo photogrammetric images
      created by the 3dMDTM Face system and models digitized using the Motion View
      scanner were utilized. Using a previous lateral cephalometric image from the
      orthodontic records appointment, these hard tissue and soft tissue images were
      integrated. RESULTS: The integration of all data sets was accomplished with an
      average error rate of less than .05mm. A method was developed, thus allowing
      measurement of soft tissue thicknesses and changes over treatment time in
      relation to the underlying dentition. CONCLUSIONS: Evaluation of hard and soft
      tissue relationship in three dimensions can be accomplished without the use of
      additional radiographic studies.

PMID- 30290098
TI  - Admissions at the University of Tennessee College of Dentistry Part 1: Trend in
      Applications 1977-2015.
AB  - This is the first in a series of commentaries related to admission to The
      University of Tennessee College of Dentistry. Admission to dental school in the
      current climate is exceedingly competitive-much more so than at any time in
      history. The purpose of the paper is to examine over thirty-five years of class
      size and total applications to the University of Tennessee College of Dentistry
      to gauge competition for admission today versus any time in the past thirty-five
      years.

PMID- 30290099
TI  - [Electrocardiographic aspects of morphogenesis of neuroleptic cardiopathy].
AB  - : Neuroleptic cardiomyopathy (NCMP) is a consequence of cardiotoxic side effect
      of antipsychotic drugs. Changes of ECG associated with this condition are poorly
      known. Aim: To elucidate dynamics of ECG at different clinical stages of NCMP and
      evaluate its diagnostic value. Methods. We determined the frequency and
      informative values of 8 different ECG signs includingQTinterval corrected based
      at theBazettformula (QTc). Their informative value was estimated from the
      Kullback formula. The data obtained were analyzed by parametric and non
      parametric statistics methods. Results: Pathological changes of ECG parameters
      associated with NCM Preflect processes of structural rearrangement in the heart
      at different levels of its organization. The analysis of the available
      information showed that almost all ECG parameters have high diagnostic value
      listed in the following rank order (frequency/informativeness): rhythm disorder -
      1/8, prolongation of the QTc interval - 4/3, conduction disorder - 2/2, diffuse
      muscular changes - 3/1, right heart overload - 5/6, left ventricular hypertrophy 
      7-8/5, impaired electrical activity of myocardium - 7-8/5, deviation of the
      electrical axis to the left - 6/4. It seems appropriate to distinguish the
      following three maximally informative (and therefore most important) ECG signs
      indicative of developing NCMP: diffuse muscular changes, conduction disorder, and
      prolongation of the QTc interval. Conclusion: The analysis of the available
      information provides a new insight into dynamics of ECG signs associated with
      NCMP and permits to estimate the diagnostic value of pathological changes for its
      earlier detection.

PMID- 30290100
TI  - [Clinico-functional phenotypes of chronic obstructive pulmonary disease, their
      influence on the severity of the disease, and prognostic value for risk
      evaluation].
AB  - Attempts at optimizing classification of chronic obstructive pulmonary disease
      (COPD) reflect clinical heterogeneity of this pathology and provide a basis for
      the search of new phenotypic markers (especially at the early stages of the
      disease) that could be useful for prognostication of its severity in individual
      patients. One of the potential makers is phenotyping of COPD with distinguishing
      bronchitic, emphysemic, and mixed phenotypes. This paper presents results of
      analysis of functional characteristics of the patients with these phenotypes.
      They are shown to reflect clinical and functional features of the disease that
      may be of value for diagnostic purposes, the choice of the treatment strategy and
      prognosis of the outcome in individual patients.

PMID- 30290101
TI  - Why Do Safety Inspections?
AB  - Work site safety inspections can be a vital part of your injury prevention
      efforts if done well.

PMID- 30290102
TI  - [Peculiarities of progression of chronic glomerulonephritis associated with
      anemia].
AB  - Aim: To study the influence of renal anemia on the clinical course of chronic
      kidney disease in patients with chronic glomerulonephritis (CGN) at the early
      stage of the disease. Materials and methods: This prospective 12 month study
      included evaluation of clinical and laboratory characteristics of 149 patients
      aged 17-66 (mean 37,6+/-12,6) years at the pre-dialysis stage of CGN (92 men
      (37,04+/-13,4 yr) and 57 women (38,2+/-11,2 yr). Results: By the end of
      prospective observation, patients of group 1 (CGN without anemia) showed a
      decrease of the hemoglobin level accompanied by the impairment of nitrogen
      releasing function with the glomerular filtration rate of 70,1 (43,1-111) ml/min
      compared with 87 (61,3-115,3) at the onset of observations (p<0,05). In group 2
      (CGN with anemia), dynamics of the nitrogen-releasing function was similar but
      even more pronounced with the glomerular filtration rate reduced to 47,4 (32,2
      91,8) ml/min compared with 80,7 (39,8-107,9) at the onset of observations
      (p<0,05) and the serum creatinine level increased to157 (92-242) mcmol/l compared
      with 123 (86-171) (p<0,05). Conclusion: Reduction of hemoglobin level in patients
      with CGN is apparent at the early stages of the disease in association with
      impairment of glomerular filtration. The data obtained indicate that anemia can
      be a laboratory predictor of deteriorated nitrogen-releasing function.

PMID- 30290103
TI  - [The problem of classification and organization of medical care for diabetic
      patients with different forms of ulcerative-necrotic lesions of lower
      extremities].
AB  - Patients with diabetes mellitus (DM) are at risk of development of both diabetic
      foot syndrome and ulcers on the lower legs due to chronic venous insufficiency
      and other factors. The main group in this study was comprised of diabetic
      patients with ulcers of different etiology (venous, post-traumatic, mixed)
      treated at the Diabetic Foot Cabinet during 5 years (n=101). The group of
      comparison included simultaneously treated patients with diabetic foot syndrome
      (n=721). Patients of the main group was dominated by women (71%) and patients
      with type 2 DM. Ulcer healing due to the treatment, persistent non-healing
      ulcers, and high-level amputations occurred equally often in the two groups: 60
      and 58%, 18 and 15%, 4 and 5% respectively (r>0,05). Lower leg ulcers in DM are
      very persistent and constitute a serious medico-social problem to be addresses
      based at Diabetic Foot cabinets. The frequency of such ulcers and related
      amputations must be taken into consideration in epidemiological surveys.

PMID- 30290104
TI  - [A case of mucoviscidosis in practical work of a pulmonologist].
AB  - A case of late manifestation ofmucoviscidosis is reported. In the past, this
      pathology was dealt with by pediatricians, but to-day the management of this
      problem involves a number of different specialists. The progress in clinical
      practice makes it possible to significantly prolong the life span of patients
      with this condition. The present case shows that its clinical manifestations may
      appear at any age.

PMID- 30290105
TI  - [Physician's anticredo from the standpoint of errologia medica: between theory
      and practice].
AB  - The author presents the clinical and methodological analysis of the problem of
      medical errors based on the empirical data obtained in the 20 century. Relevant
      theoretical premises having applied implications are substantiated.

PMID- 30290106
TI  - The Importance of Arc Flash Mitigation.
AB  - De-energizing equipment does not absolve the facility from the responsibility of
      performing an arc flash analysis or providing the necessary PPE.

PMID- 30290107
TI  - Identify, Verify, and Comply: The Three Pillars of a Successful Electrical Safety
      Program.
AB  - What's shocking is that many workers are not using rubber insulating equipment
      because they simply don't know they need it.

PMID- 30290108
TI  - OnStar for Your Gas Detection Program.
AB  - How are organizations leveraging historical and real-time data to keep workers
      safe? As with auto safety systems and services, one type of data isn't enough for
      your gas detection program.

PMID- 30290109
TI  - ASSE's Mile High Moment.
AB  - This could be the most consequential annual conference for the society in many
      years.

PMID- 30290110
TI  - Safety Totally Leads the Way.
AB  - This is not just the path toward improved safety and lower safety-related costs;
      it is also the path to walk if your goal is greater customer retention, higher
      sales, and maximizing profits.

PMID- 30290111
TI  - Does Your Safety Incentive Program Need More Carrot and Less Stick?
AB  - Safety training is the best way to ensure your procedures are understood and a
      great way to reinforce safe behaviors. It reinforces your safety goals and
      reminds participants about the impacts of not achieving those goals.

PMID- 30290112
TI  - Encouraging Hands-Only  CPR.
AB  - A study published in Circulation last year found that CPR knowledge and
      confidence to use hands-only CPR can be increased through large-scale community
      training.

PMID- 30290113
TI  - Eight Things Oil & Gas Workers Should Know About Flash Fires.
AB  - Flash fires and fuel-fed fires are two different hazards, and it's critical to
      distinguish between the two for various safety reasons.

PMID- 30290114
TI  - The Significance of API RP 2219 Recommendations in the BLSR Accident, Part II.
AB  - Employers and workers need to pay special attention to minimum recommended safety
      requirements of approved standards and safe working procedures.

PMID- 30290115
TI  - Renewable Hydride Donors for the Catalytic Reduction of CO2: A Thermodynamic and
      Kinetic Study.
AB  - Increasing atmospheric CO2 concentration and dwindling fossil fuel supply
      necessitate the search for efficient methods for CO2 conversion to fuels.
      Assorted studies have shown pyridine and its derivatives capable of
      (photo)electrochemically reducing CO2 to methanol, and some mechanistic
      interpretations have been proposed. Here, we analyze the thermodynamic and
      kinetic aspects of the efficacy of pyridines as hydride-donating catalytic
      reagents that transfer hydrides via their dihydropyridinic form. We investigate
      both the effects of functionalizing pyridinic derivatives with electron-donating
      and electron-withdrawing groups on hydride-transfer catalyst strength, assessed
      via their hydricity (thermodynamic ability) and nucleophilicity (kinetic
      ability), and catalyst recyclability, assessed via their reduction potential. We
      find that pyridines substituted with electron-donating groups have stronger
      hydride-donating ability (having lower hydricity and larger nucleophilicity
      values), but are less efficiently recycled (having more negative reduction
      potentials). In contrast, pyridines substituted with electron-withdrawing groups
      are more efficiently recycled, but are weaker hydride donors. Functional group
      modification favorably tunes hydride strength or efficiency, but not both. We
      attribute this problematic coupling between the strength and recyclability of
      pyridinic hydrides to their aromatic nature and suggest several avenues for
      overcoming this difficulty.

PMID- 30290116
TI  - Ionic-Strength Effects on the Reactive Uptake of Ozone on Aqueous Pyruvic Acid:
      Implications for Air-Sea Ozone Deposition.
AB  - A vertical wetted-wall flow-tube technique was used to explore the ionic strength
      effects at the air-water interface in mediating the sea-surface reaction between
      ozone (O3) and pyruvic acid (PA). The uptake coefficients of ozone on aqueous PA
      increase substantially with the concentrations of bromide (Br-) ions, clearly
      indicating that the dry deposition of ozone could be significantly enhanced due
      to the presence of carbonyl compounds such as PA at the bromide-rich sea surface.
      Based on the observed uptake coefficients, the estimated deposition velocity of
      ozone (100 ppb) for a nanomolar range of PA concentrations is ~1 * 10-3 m s-1,
      which represents a significant contribution to the known deposition velocity of
      ozone at the sea surface. The analysis of reaction products by ultra-high
      resolution Fourier transform-ion cyclotron resonance mass spectrometry suggests
      the formation of oligomers during both the dark and light-induced heterogeneous
      reactions between gaseous O3 and PA occurring at the surface of a dilute aqueous
      phase (representative of cloud droplets). The detected high-molecular-weight
      compounds are much more complex than the oligomeric species identified during the
      photolytic degradation of bulk aqueous PA alone.

PMID- 30290117
TI  - Real Time Normalization of Fast Photochemical Oxidation of Proteins Experiments
      by Inline Adenine Radical Dosimetry.
AB  - Hydroxyl radical protein footprinting (HRPF) is a powerful method for measuring
      protein topography, allowing researchers to monitor events that alter the solvent
      accessible surface of a protein (e.g., ligand binding, aggregation,
      conformational changes, etc.) by measuring changes in the apparent rate of
      reaction of portions of the protein to hydroxyl radicals diffusing in solution.
      Fast Photochemical Oxidation of Proteins (FPOP) offers an ultrafast benchtop
      method for radical generation for HRPF, photolyzing hydrogen peroxide using a UV
      laser to generate high concentrations of hydroxyl radicals that are consumed on
      roughly a microsecond time scale. The broad reactivity of hydroxyl radicals means
      that almost anything added to the solution (e.g., ligands, buffers, excipients,
      etc.) will scavenge hydroxyl radicals, altering their half-life and changing the
      effective radical concentration experienced by the protein. Similarly, minute
      changes in peroxide concentration, laser fluence, and buffer composition can
      alter the effective radical concentration, making reproduction of data
      challenging. Here, we present a simple method for radical dosimetry that can be
      carried out as part of the FPOP workflow, allowing for measurement of effective
      radical concentration in real time. Additionally, by modulating the amount of
      radical generated, we demonstrate that effective hydroxyl radical yields in FPOP
      HRPF experiments carried out in buffers with widely differing levels of hydroxyl
      radical scavenging capacity can be compensated on the fly, yielding statistically
      indistinguishable results for the same conformer. This method represents a major
      step in transforming FPOP into a robust and reproducible technology capable of
      probing protein structure in a wide variety of contexts.

PMID- 30290118
TI  - Woven Kevlar Fiber/Polydimethylsiloxane/Reduced Graphene Oxide Composite-Based
      Personal Thermal Management with Freestanding Cu-Ni Core-Shell Nanowires.
AB  - Thermotherapy is a widespread technique that provides relief for muscle spasms
      and joint injuries. A great deal of energy is used to heat the surrounding
      environment, and heat emitted by the human body is wasted on our surroundings.
      Herein, a woven Kevlar fiber (WKF)-based personal thermal management device was
      fabricated by directly growing vertical copper-nickel (Cu-Ni) nanowires (NWs) on
      the WKF surface using a hydrothermal method. The treated WKF was combined with
      reduced graphene oxide (rGO) dispersed in polydimethylsiloxane (PDMS) to form
      composites using vacuum-assisted resin transfer molding (VARTM). This WKF-based
      personal thermal management system contained a conductive network of metallic NWs
      and rGO that promoted effective Joule heating and reflected back the infrared
      (IR) radiation emitted by the human body. It thus behaved as a type of thermal
      insulation. The Cu-Ni NWs were synthesized with a tunable Ni layer on Cu core NWs
      to enhance the oxidation resistance of the Cu NWs. The combined effect of the NW
      networks and rGO enabled a surface temperature of 70  degrees C to be attained on
      application of 1.5 V to the composites. The Cu3Ni1-WKF/PDMS provided 43% more
      thermal insulation and higher IR reflectance than bare WKF/PDMS. The absorbed
      impact energy and tensile strength was highest for the Cu1Ni3- and rGO-integrated
      WKF/PDMS samples. Those Cu-Ni NWs having higher Ni contents displayed better
      mechanical properties and those with higher Cu contents showed higher Joule
      heating performance and IR reflectivity at a given rGO loading. The composite
      shows sufficient breathability and very high durability. The high flexibility of
      the composites and their ability to generate sufficient heat during various human
      motions ensures their suitability for wearable applications.

PMID- 30290119
TI  - CRISPro: An Automated Pipeline for Protein Conformation Stabilization by Proline.
AB  - Recent studies have shown that the yield, antigenicity, and immunogenicity of an
      immunogen can be enhanced by stabilizing it into a specific conformation. Such
      stabilization often involves the engineering of proline mutations at residue
      positions where a proline is structurally compatible with the target conformation
      but not with an alternative conformation. However, there is no publicly available
      tool that can design proline mutations for this purpose automatically. Here we
      implemented an automated tool, CRISPro, that inputs structural coordinates of the
      target conformation and/or an alternative conformation and outputs a list of
      residue positions where proline mutations are predicted to stabilize the target
      conformation based on compatibility of phi-psi angles, secondary structure, and
      steric constraints. Thus, CRISPro can be used to engineer immunogens into
      specific conformation and to design serologic probes, capable of isolating
      antibodies that recognize a target shape.

PMID- 30290120
TI  - Reply to: Dysfunctional Immunity and Microbial Adhesion Molecules in Smoking
      Induced Pneumonia.

PMID- 30290121
TI  - Financial Incentives Promote Smoking Cessation Directly, Not by Increasing Use of
      Cessation Aids.

PMID- 30290122
TI  - Cell-Based Therapy for Bronchopulmonary Dysplasia in Preterm Infants: Workshop
      report.
AB  - Bronchopulmonary dysplasia (BPD) is the most common complication of extreme
      prematurity. Currently, there is no specific treatment available. Preclinical
      studies support cell-therapy as a promising therapy for BPD in preterm infants. A
      successful translation to a safe and effective clinical intervention depends on
      multiple factors including the perspective of neonatal health care providers. A 2
      hour workshop with 40 Canadian neonatologists was held to enhance the design of a
      phase II trial of stem cells for babies at risk for BPD, with a focus on the
      population to target and the outcomes to measure in such a trial. The consensus
      was that infants recruited in an early trial of stem cells should be the ones
      with the highest risk of developing severe BPD. This risk should be established
      based on known antenatal, perinatal and postnatal risk factors. The primary
      outcome in a phase II trial will be focussed on a non-clinical outcome (e.g. a
      dose finding- or a safety-study). With other aspects of a translational study
      discussed, this workshop contributed to accelerate the design of a first Canadian
      clinical cell-therapy study for BPD in preterm infants.

PMID- 30290123
TI  - Inhibition of microRNA-155 attenuates concanavalin-A-induced autoimmune hepatitis
      by regulating Treg/Th17 cell differentiation.
AB  - Autoimmune hepatitis (AIH) is a chronic progressive autoimmune disease
      characterized by hepatic inflammation. This study aimed to investigate the effect
      of antagomir-155 on concanavalin A (ConA)-induced AIH, and its possible
      mechanisms. According to the results, the expression of miR-155 was raised in
      liver tissues after 48 h exposure to ConA. Treatment with antagomir-155
      attenuated ConA-induced liver injury in mice by reducing serum alanine
      aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels. In
      addition, antagomir-155 significantly alleviated the differentiation of Treg/Th17
      cells in the livers of AIH mice, and suppressed Th17-cells-mediated production of
      pro-inflammatory cytokines IL-17A, IL-23, but not Treg-cells-mediated production
      of anti-inflammatory cytokine IL-10. Finally, the beneficial effect of antagomir
      155 on ConA-induced AIH was abolished by administration of recombinant IL-17A.
      Our data demonstrated that antagomir-155 treatment could prevent AIH via
      regulating the differentiation of Treg and Th17 cells, suggesting that microRNA
      155 may be an intriguing therapeutic target of AIH.

PMID- 30290124
TI  - Myeloid TBK1 Signaling Contributes to the Immune Response to Influenza.
AB  - Macrophages provide key elements of the host response to influenza A virus (IAV)
      infection, including expression of type I interferon (IFN) and inflammatory
      cytokines and chemokines. TANK-binding kinase 1 (TBK1) contributes to IFN
      expression and anti-viral responses in some cell types, but its role in the
      innate response to IAV in vivo is unknown. We hypothesized that macrophage TBK1
      contributes to both IFN and non-IFN components of host defense and IAV pathology.
      We generated myeloid-conditional TBK1 knockout mice and assessed the in vitro and
      in vivo consequences of IAV infection. Myeloid-specific loss of TBK1 in vivo
      resulted in less severe host response to IAV, as assessed by decreased mortality,
      weight loss, and hypoxia and less inflammatory changes in BALF relative to
      wildtype (WT) mice despite no differences in viral load. Mice lacking myeloid
      TBK1 showed less recruitment of CD64+SiglecF-Ly6Chi inflammatory macrophages
      (InfMs), less expression of inflammatory cytokines in the BALF, and less
      expression of both interferon regulatory factor (IRF) and NF-kappaB target genes
      in the lung. Analysis of sorted AMs, InfMs, and lung interstitial macrophages
      (IMs) revealed that each subpopulation requires TBK1 for distinct components of
      the response to IAV infection. Our findings define roles for myeloid TBK1 in IAV
      induced lung inflammation apart from IFN type I expression and point to myeloid
      TBK1 as a central and cell type-specific regulator of virus-induced lung damage.

PMID- 30290125
TI  - Dysfunctional Immunity and Microbial Adhesion Molecules in Smoking-Induced
      Pneumonia.

PMID- 30290126
TI  - Design of the LifeArc Index Set and Retrospective Review of Its Performance: A
      Collection for Sharing.
AB  - Building, curating, and maintaining a compound collection is an expensive
      operation, beyond the scope of most academic organizations. Here we describe the
      selection criteria used to compile the LifeArc diversity set from commercial
      suppliers and the process we undertook to generate our representative LifeArc
      index set. The aim was to avoid a "junk in, junk out" screen collection to
      increase chemical tractability going forward, while maximizing diversity. Using
      historical LifeArc screening data, we demonstrate that the index set was
      predictive of ligandability and that progressable hits could be identified by
      mining associated clusters within our larger diversity set. Indeed, a higher
      percentage of index-derived hit clusters were found to have been progressed into
      hit-to-lead programs, reflecting better drug-likeness. In practice, the library
      has been shared widely with academic groups and used routinely within LifeArc to
      assess the ligandability of novel targets. Its small size is well suited to meet
      the needs of medium-throughput screening in labs with either limited automation,
      limited precious or expensive reagents, or complex cellular assays. The strategy
      of screening a small set in combination with rapid hit analog follow-up has
      demonstrated the utility of finding active clusters for potential development
      against challenging targets.

PMID- 30290128
TI  - High-Throughput DNA Plasmid Transfection Using Acoustic Droplet Ejection
      Technology.
AB  - The Labcyte Echo acoustic liquid handler allows accurate droplet ejection at high
      speed from a source well plate to a destination plate. It has already been used
      in various miniaturized biological assays, such as quantitative PCR (q-PCR),
      quantitative real-time PCR (q-RT-PCR), protein crystallization, drug screening,
      cell dispensing, and siRNA transfection. However, no plasmid DNA transfection
      assay has been published so far using this dispensing technology. In this study,
      we evaluated the ability of the Echo 550 device to perform plasmid DNA
      transfection in 384-well plates. Due to the high throughput of this device, we
      simultaneously optimized the three main parameters of a transfection process:
      dilution of the transfection reagent, DNA amount, and starting DNA concentration.
      We defined a four-step protocol whose optimal settings allowed us to transfect
      HeLa cells with up to 90% efficiency and reach a co-expression of nearly 100%
      within transfected cells in co-transfection experiments. This fast, reliable, and
      automated protocol opens new ways to easily and rapidly identify optimal
      transfection settings for a given cell type. Furthermore, it permits easy
      software-based transfection control and multiplexing of plasmids distributed on
      wells of a source plate. This new development could lead to new array
      applications, such as human ORFeome protein expression or CRISPR-Cas9-based gene
      function validation in nonpooled screening strategies.

PMID- 30290127
TI  - Structural and Functional Lung Impairment in Primary Ciliary Dyskinesia.
      Assessment with Magnetic Resonance Imaging and Multiple Breath Washout in
      Comparison to Spirometry.
AB  - RATIONALE: Primary ciliary dyskinesia (PCD) is an inherited disorder
      characterized by heterogeneous airway disease. Traditional lung function
      techniques (e.g., spirometry) may underestimate severity and complexity of PCD.
      OBJECTIVES: We assessed lung impairment in individuals with PCD using structural
      and functional magnetic resonance imaging (MRI) and different lung function
      techniques. METHODS: A total of 30 study participants with PCD (median, 13.4 yr;
      range, 5-28 yr) underwent structural and functional MRI, spirometry, and multiple
      breath washout (MBW) on the same day. Primary endpoints included structural MRI
      morphology scores, relative ventilation, and perfusion impairment from functional
      MRI, forced expiratory volume in 1 second (FEV1) from spirometry, and lung
      clearance index (LCI) from MBW. RESULTS: Severity and complexity of PCD lung
      disease varied significantly between individuals. Structural lung disease was
      detected in all subjects with a median (interquartile range) extent score of 10.3
      (7-19; maximum score = 60). Functional MRI ventilation impairment was present in
      52% of subjects, affecting 24.2% (21.1 to 25.2%) of the lung. Relative perfusion
      impairment was detected in 78% of individuals affecting 21.1% (19.4 to 25.9%) of
      the lung. LCI was abnormal in 83% (median, 8.3 [2.6 to 13.2] z-scores) and FEV1
      was abnormal in 27% (-0.5 [-1.6 to 0.3] z-scores) of individuals. Concordance
      between spirometry and imaging outcomes was poor, with 52% of patients showing
      both abnormal MRI and LCI values, but normal FEV1. CONCLUSIONS: Discordance
      between lung function and imaging outcomes in patients with PCD supports the use
      of both imaging and lung function, such as MBW, for surveillance of this
      heterogeneous disease.

PMID- 30290129
TI  - Special Delivery: A New Package for an Old Anti-Fibrotic Mediator.

PMID- 30290130
TI  - Nonrestorative Treatments for Caries: Systematic Review and Network Meta
      analysis.
AB  - The goal of nonrestorative or non- and microinvasive caries treatment (fluoride-
      and nonfluoride-based interventions) is to manage the caries disease process at a
      lesion level and minimize the loss of sound tooth structure. The purpose of this
      systematic review and network meta-analysis was to summarize the available
      evidence on nonrestorative treatments for the outcomes of 1) arrest or reversal
      of noncavitated and cavitated carious lesions on primary and permanent teeth and
      2) adverse events. We included parallel and split-mouth randomized controlled
      trials where patients were followed for any length of time. Studies were
      identified with MEDLINE and Embase via Ovid, Cochrane CENTRAL, and Cochrane
      Database of Systematic Reviews. Pairs of reviewers independently conducted the
      selection of studies, data extraction, risk-of-bias assessments, and assessment
      of the certainty in the evidence with the Grading of Recommendations Assessment,
      Development, and Evaluation (GRADE) approach. Data were synthesized with a random
      effects model and a frequentist approach. Forty-four trials (48 reports) were
      eligible, which included 7,378 participants and assessed the effect of 22
      interventions in arresting or reversing noncavitated or cavitated carious
      lesions. Four network meta-analyses suggested that sealants + 5% sodium fluoride
      (NaF) varnish, resin infiltration + 5% NaF varnish, and 5,000-ppm F (1.1% NaF)
      toothpaste or gel were the most effective for arresting or reversing noncavitated
      occlusal, approximal, and noncavitated and cavitated root carious lesions on
      primary and/or permanent teeth, respectively (low- to moderate-certainty
      evidence). Study-level data indicated that 5% NaF varnish was the most effective
      for arresting or reversing noncavitated facial/lingual carious lesions (low
      certainty) and that 38% silver diamine fluoride solution applied biannually was
      the most effective for arresting advanced cavitated carious lesions on any
      coronal surface (moderate to high certainty). Preventing the onset of caries is
      the ultimate goal of a caries management plan. However, if the disease is
      present, there is a variety of effective interventions to treat carious lesions
      nonrestoratively.

PMID- 30290131
TI  - Caring for Critically Ill Patients in Humanitarian Settings.
AB  - Critical care medicine is far from the first medical field to come to mind when
      humanitarian action is mentioned, yet both critical care and humanitarian action
      share a fundamental purpose to save lives and ease suffering of people caught in
      acute crises. Critically ill children and adults will be present regardless of
      resources limitations, irrespective of geography, regional/cultural contexts,
      insecurity or socioeconomic status and they may be even more prevalent in a
      humanitarian crisis. Critical care is not limited to the walls of a hospital and
      all hospitals will have critically ill patients regardless of designating a
      specific ward an Intensive Care Unit. Regular and consistent consideration of
      critical care principles in humanitarian settings provides crucial guidance to
      Intensivists and non-Intensivists alike. A multi-disciplinary, systematic
      approach to patient care that encourages critical thinking, checklists which
      encourage communication amongst team members, and context-specific critical care
      rapid response teams are examples of critical care constructs that can provide
      high quality critical care in all environments. Promoting critical care
      principles conveys the message that critical care is an integral part of
      healthcare and should be accessible to all, no matter the setting. These
      principles can be effectively adopted in humanitarian settings by normalizing
      them to everyday clinical practice. Equally, core humanitarian principles -
      dignity, accountability, impartiality, neutrality - can be applied to critical
      care. Applying principles of critical care in a context-specific manner and
      applying humanitarian principles to critical care can improve the quality of
      patient care and transcend barriers to resource limitations.

PMID- 30290132
TI  - Ezrin, a Membrane Cytoskeleton Cross Linker Protein, as a Marker of Epithelial
      Damage in Asthma.
AB  - RATIONALE: Bronchial epithelial cell damage occurs in patients with bronchial
      asthma. Ezrin, a membrane-cytoskeleton protein, maintains cellular morphology and
      intercellular adhesion and protects the barrier function of epithelial cells.
      OBJECTIVES: To study the role of ezrin in bronchial epithelial cells injury and
      correlate its expression with asthma severity. METHODS: Levels of ezrin were
      measured in exhaled breath condensate (EBC) and serum in asthma patients and
      bronchoalveolar lavage fluid (BALF) from a mouse model of asthma by ELISA. The
      regulation of IL-13 on ezrin protein levels was studied in primary bronchial
      epithelial cells (PBECs). Ezrin knockdown using shRNA was studied in human
      bronchial epithelial 16HBE cells. RESULTS: Ezrin levels were decreased in
      asthmatic EBC (392.7+/-34.99 vs 150.5+/-10.22 pg/ml, p<0.0001) and serum (700.7+/
      55.59 vs 279.2+/-25.83pg/ml, p<0.0001) compared to normal subjects. Levels were
      much lower in uncontrolled (p<0.001) and partly-controlled patients (p<0.01)
      compared to well-controlled subjects. EBC and serum ezrin levels correlated with
      lung function in asthma patients and serum ezrin levels were negatively
      correlated with serum IL-13 and periostin. IL-13-induced down-regulation of ezrin
      expression in PBECs was significantly attenuated by the JAK2 (Janus tyrosine
      kinase 2) inhibitor TG101348. Ezrin knockdown changed 16HBE cell morphology,
      enlarged intercellular spaces and increased their permeability. Ezrin expression
      was decreased in the lung tissue and BALF of 'asthmatic' mice and negatively
      correlated with BALF IL-13 level. CONCLUSIONS: Ezrin down-regulation is
      associated with IL-13-induced epithelial damage and might be a potential
      biomarker of asthma control.

PMID- 30290134
TI  - Addressing Diversity and Inclusion in Human Genetics Research.

PMID- 30290133
TI  - Interred with Their DNA.

PMID- 30290135
TI  - Simultaneous Viral Exposure and Protection from Neanderthal Introgression.
AB  - In this issue, Enard and Petrov present intriguing results on the possibility of
      genetic traces left behind in our genomes from adaptation to past viral epidemics
      that may have been initiated by interaction with Neanderthal archaic hominins.
      The work highlights how powerful infectious agents can act as a selective force
      to shape our genetic makeup.

PMID- 30290136
TI  - Aster: A New Star in Cholesterol Trafficking.
AB  - Life evolved in an aqueous environment, necessitating the evolution of carrier
      proteins to shuttle lipophilic molecules within and between cells. Sandhu et. al.
      (2018) report the discovery of a long-sought-after cholesterol carrier protein,
      named Aster, which transports cholesterol from the plasma membrane to the
      endoplasmic reticulum.

PMID- 30290137
TI  - Exposing a Virus Hiding in the Animal Facility.
AB  - Roediger et al. (2018) demonstrate that a kidney disease characterized by
      apparently spontaneous nephropathy that had been recognized in laboratory mice
      for many years is caused by a newly recognized virus named the mouse kidney
      parvovirus (MKPV). That virus appears to be widespread in mouse colonies as it is
      not detected by current diagnostic tools, and its recognition presents new
      opportunities for understanding the pathology of tubulointerstitial fibrosis.

PMID- 30290138
TI  - Bacterial Siderophores Promote Animal Host Iron Acquisition and Growth.
AB  - Siderophores are small molecules produced by bacteria that bind ferric iron in
      the surrounding environment with extraordinary affinity. A new study provides
      evidence that a simple animal host, Caenorhabditis elegans, co-opts siderophores
      to promote its own iron acquisition and growth.

PMID- 30290139
TI  - A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization.
AB  - Harnessing an antitumor immune response has been a fundamental strategy in cancer
      immunotherapy. For over a century, efforts have primarily focused on amplifying
      immune activation mechanisms that are employed by humans to eliminate invaders
      such as viruses and bacteria. This "immune enhancement" strategy often results in
      rare objective responses and frequent immune-related adverse events (irAEs).
      However, in the last decade, cancer immunotherapies targeting the B7-H1/PD-1
      pathway (anti-PD therapy), have achieved higher objective response rates in
      patients with much fewer irAEs. This more beneficial tumor response-to-toxicity
      profile stems from distinct mechanisms of action that restore tumor-induced
      immune deficiency selectively in the tumor microenvironment, here termed "immune
      normalization," which has led to its FDA approval in more than 10 cancer
      indications and facilitated its combination with different therapies. In this
      article, we wish to highlight the principles of immune normalization and learn
      from it, with the ultimate goal to guide better designs for future cancer
      immunotherapies.

PMID- 30290140
TI  - The Cellular and Molecular Basis for Planarian Regeneration.
AB  - Regeneration is one of the great mysteries of biology. Planarians are flatworms
      capable of dramatic feats of regeneration, which have been studied for over 2
      centuries. Recent findings identify key cellular and molecular principles
      underlying these feats. A stem cell population (neoblasts) generates new cells
      and is comprised of pluripotent stem cells (cNeoblasts) and fate-specified cells
      (specialized neoblasts). Positional information is constitutively active and
      harbored primarily in muscle, where it acts to guide stem cell-mediated tissue
      turnover and regeneration. I describe here a model in which positional
      information and stem cells combine to enable regeneration.

PMID- 30290141
TI  - Genomic Analyses from Non-invasive Prenatal Testing Reveal Genetic Associations,
      Patterns of Viral Infections, and Chinese Population History.
AB  - We analyze whole-genome sequencing data from 141,431 Chinese women generated for
      non-invasive prenatal testing (NIPT). We use these data to characterize the
      population genetic structure and to investigate genetic associations with
      maternal and infectious traits. We show that the present day distribution of
      alleles is a function of both ancient migration and very recent population
      movements. We reveal novel phenotype-genotype associations, including several
      replicated associations with height and BMI, an association between maternal age
      and EMB, and between twin pregnancy and NRG1. Finally, we identify a unique
      pattern of circulating viral DNA in plasma with high prevalence of hepatitis B
      and other clinically relevant maternal infections. A GWAS for viral infections
      identifies an exceptionally strong association between integrated herpesvirus 6
      and MOV10L1, which affects piwi-interacting RNA (piRNA) processing and PIWI
      protein function. These findings demonstrate the great value and potential of
      accumulating NIPT data for worldwide medical and genetic analyses.

PMID- 30290142
TI  - Evidence that RNA Viruses Drove Adaptive Introgression between Neanderthals and
      Modern Humans.
AB  - Neanderthals and modern humans interbred at least twice in the past 100,000
      years. While there is evidence that most introgressed DNA segments from
      Neanderthals to modern humans were removed by purifying selection, less is known
      about the adaptive nature of introgressed sequences that were retained. We
      hypothesized that interbreeding between Neanderthals and modern humans led to (1)
      the exposure of each species to novel viruses and (2) the exchange of adaptive
      alleles that provided resistance against these viruses. Here, we find that long,
      frequent-and more likely adaptive-segments of Neanderthal ancestry in modern
      humans are enriched for proteins that interact with viruses (VIPs). We found that
      VIPs that interact specifically with RNA viruses were more likely to belong to
      introgressed segments in modern Europeans. Our results show that retained
      segments of Neanderthal ancestry can be used to detect ancient epidemics.

PMID- 30290144
TI  - The Human Transcription Factors.

PMID- 30290143
TI  - Immune Checkpoint Inhibition Overcomes ADCP-Induced Immunosuppression by
      Macrophages.
AB  - Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular
      phagocytosis (ADCP) critically contribute to the efficacy of anti-tumor
      therapeutic antibodies. We report here an unexpected finding that macrophages
      after ADCP inhibit NK cell-mediated ADCC and T cell-mediated cytotoxicity in
      breast cancers and lymphomas. Mechanistically, AIM2 is recruited to the
      phagosomes by FcgammaR signaling following ADCP and activated by sensing the
      phagocytosed tumor DNAs through the disrupted phagosomal membrane, which
      subsequently upregulates PD-L1 and IDO and causes immunosuppression. Combined
      treatment with anti-HER2 antibody and inhibitors of PD-L1 and IDO enhances anti
      tumor immunity and anti-HER2 therapeutic efficacy in mouse models. Furthermore,
      neoadjuvant trastuzumab therapy significantly upregulates PD-L1 and IDO in the
      tumor-associated macrophages (TAMs) of HER2+ breast cancer patients, correlating
      with poor trastuzumab response. Collectively, our findings unveil a deleterious
      role of ADCP macrophages in cancer immunosuppression and suggest that therapeutic
      antibody plus immune checkpoint blockade may provide synergistic effects in
      cancer treatment.

PMID- 30290146
TI  - Cancer Mutations in SPOP Put a Stop to Its Inter-compartmental Hops.
AB  - In this issue of Molecular Cell, Bouchard et al. (2018) identify liquid-liquid
      phase separation as a mechanism for substrate-triggered localization of SPOP and
      ubiquitination machinery to different nuclear bodies and describe how cancer
      mutations disrupt this process.

PMID- 30290145
TI  - SnapShot: RNA Structure Probing Technologies.
AB  - Chemical probing coupled to high-throughput sequencing offers a flexible approach
      to uncover many aspects of RNA structure relevant to its cellular function. With
      a wide variety of chemical probes available that each report on different
      features of RNA molecules, a broad toolkit exists for investigating in vivo and
      in vitro RNA structure and interactions with other molecules.

PMID- 30290147
TI  - Transcript Buffering: A Balancing Act between mRNA Synthesis and mRNA
      Degradation.
AB  - Transcript buffering involves reciprocal adjustments between overall rates in
      mRNA synthesis and degradation to maintain similar cellular concentrations of
      mRNAs. This phenomenon was first discovered in yeast and encompasses coordination
      between the nuclear and cytoplasmic compartments. Transcript buffering was
      revealed by novel methods for pulse labeling of RNA to determine in vivo
      synthesis and degradation rates. In this Perspective, we discuss the current
      knowledge of transcript buffering. Emphasis is placed on the future challenges to
      determine the nature and directionality of the buffering signals, the generality
      of transcript buffering beyond yeast, and the molecular mechanisms responsible
      for this balancing.

PMID- 30290148
TI  - Entering the Pocket: Crystal Structure of a Prostaglandin D2 Receptor.
AB  - In this issue of Molecular Cell, crystal structures of a prostaglandin D2
      receptor determined by Wang et al. (2018) reveal novel insights into differential
      ligand recognition among the members of lipid-binding GPCRs, and provide a
      structural framework for the identification of novel therapeutics in inflammatory
      disorders.

PMID- 30290149
TI  - RNA Velocity: Molecular Kinetics from Single-Cell RNA-Seq.
AB  - Applying a kinetic model of RNA transcription and splicing, La Manno et al.
      (2018) predict changes in mRNA levels of individual cells from single-cell RNA
      seq data.

PMID- 30290150
TI  - Phenotype-Specific Enrichment of Mendelian Disorder Genes near GWAS Regions
      across 62 Complex Traits.
AB  - Although recent studies provide evidence for a common genetic basis between
      complex traits and Mendelian disorders, a thorough quantification of their
      overlap in a phenotype-specific manner remains elusive. Here, we have quantified
      the overlap of genes identified through large-scale genome-wide association
      studies (GWASs) for 62 complex traits and diseases with genes containing
      mutations known to cause 20 broad categories of Mendelian disorders. We
      identified a significant enrichment of genes linked to phenotypically matched
      Mendelian disorders in GWAS gene sets; of the total 1,240 comparisons, a higher
      proportion of phenotypically matched or related pairs (n = 50 of 92 [54%]) than
      phenotypically unmatched pairs (n = 27 of 1,148 [2%]) demonstrated significant
      overlap, confirming a phenotype-specific enrichment pattern. Further, we observed
      elevated GWAS effect sizes near genes linked to phenotypically matched Mendelian
      disorders. Finally, we report examples of GWAS variants localized at the
      transcription start site or physically interacting with the promoters of genes
      linked to phenotypically matched Mendelian disorders. Our results are consistent
      with the hypothesis that genes that are disrupted in Mendelian disorders are
      dysregulated by non-coding variants in complex traits and demonstrate how
      leveraging findings from related Mendelian disorders and functional genomic
      datasets can prioritize genes that are putatively dysregulated by local and
      distal non-coding GWAS variants.

PMID- 30290153
TI  - Activating Mutations in PAK1, Encoding p21-Activated Kinase 1, Cause a
      Neurodevelopmental Disorder.
AB  - p21-activated kinases (PAKs) are serine/threonine protein kinases acting as
      effectors of CDC42 and RAC, which are members of the RHO family of small GTPases.
      PAK1's kinase activity is autoinhibited by homodimerization, whereas CDC42 or
      RAC1 binding causes PAK1 activation by dimer dissociation. Major functions of the
      PAKs include actin cytoskeleton reorganization, for example regulation of the
      cellular protruding activity during cell spreading. We report the de novo PAK1
      mutations c.392A>G (p.Tyr131Cys) and c.1286A>G (p.Tyr429Cys) in two unrelated
      subjects with developmental delay, secondary macrocephaly, seizures, and ataxic
      gait. We identified enhanced phosphorylation of the PAK1 targets JNK and AKT in
      fibroblasts of one subject and of c-JUN in those of both subjects compared with
      control subjects. In fibroblasts of the two affected individuals, we observed a
      trend toward enhanced PAK1 kinase activity. By using co-immunoprecipitation and
      size-exclusion chromatography, we observed a significantly reduced dimerization
      for both PAK1 mutants compared with wild-type PAK1. These data demonstrate that
      the two PAK1 variants function as activating alleles. In a cell spreading assay,
      subject-derived fibroblasts showed significant enrichment in cells occupied by
      filopodia. Interestingly, application of the PAK1 inhibitor FRAX486 completely
      reversed this cellular phenotype. Together, our data reveal that dominantly
      acting, gain-of-function PAK1 mutations cause a neurodevelopmental phenotype with
      increased head circumference, possibly by a combined effect of defective
      homodimerization and enhanced kinase activity of PAK1. This condition, along with
      the developmental disorders associated with RAC1 and CDC42 missense mutations,
      highlight the importance of RHO GTPase members and effectors in neuronal
      development.

PMID- 30290151
TI  - A Recurrent De Novo Heterozygous COG4 Substitution Leads to Saul-Wilson Syndrome,
      Disrupted Vesicular Trafficking, and Altered Proteoglycan Glycosylation.
AB  - The conserved oligomeric Golgi (COG) complex is involved in intracellular
      vesicular transport, and is composed of eight subunits distributed in two lobes,
      lobe A (COG1-4) and lobe B (COG5-8). We describe fourteen individuals with Saul
      Wilson syndrome, a rare form of primordial dwarfism with characteristic facial
      and radiographic features. All affected subjects harbored heterozygous de novo
      variants in COG4, giving rise to the same recurrent amino acid substitution
      (p.Gly516Arg). Affected individuals' fibroblasts, whose COG4 mRNA and protein
      were not decreased, exhibited delayed anterograde vesicular trafficking from the
      ER to the Golgi and accelerated retrograde vesicular recycling from the Golgi to
      the ER. This altered steady-state equilibrium led to a decrease in Golgi volume,
      as well as morphologic abnormalities with collapse of the Golgi stacks. Despite
      these abnormalities of the Golgi apparatus, protein glycosylation in sera and
      fibroblasts from affected subjects was not notably altered, but decorin, a
      proteoglycan secreted into the extracellular matrix, showed altered Golgi
      dependent glycosylation. In summary, we define a specific heterozygous COG4
      substitution as the molecular basis of Saul-Wilson syndrome, a rare skeletal
      dysplasia distinct from biallelic COG4-CDG.

PMID- 30290152
TI  - Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts.
AB  - Infantile and childhood-onset cataracts form a heterogeneous group of disorders;
      among the many genetic causes, numerous pathogenic variants in additional genes
      associated with autosomal-recessive infantile cataracts remain to be discovered.
      We identified three consanguineous families affected by bilateral infantile
      cataracts. Using exome sequencing, we found homozygous loss-of-function variants
      in DNMBP: nonsense variant c.811C>T (p.Arg271*) in large family F385 (nine
      affected individuals; LOD score = 5.18 at theta = 0), frameshift deletion
      c.2947_2948del (p.Asp983*) in family F372 (two affected individuals), and
      frameshift variant c.2852_2855del (p.Thr951Metfs*41) in family F3 (one affected
      individual). The phenotypes of all affected individuals include infantile-onset
      cataracts. RNAi-mediated knockdown of the Drosophila ortholog still life (sif),
      enriched in lens-secreting cells, affects the development of these cells as well
      as the localization of E-cadherin, alters the distribution of septate junctions
      in adjacent cone cells, and leads to a ~50% reduction in electroretinography
      amplitudes in young flies. DNMBP regulates the shape of tight junctions, which
      correspond to the septate junctions in invertebrates, as well as the assembly
      pattern of E-cadherin in human epithelial cells. E-cadherin has an important role
      in lens vesicle separation and lens epithelial cell survival in humans. We
      therefore conclude that DNMBP loss-of-function variants cause infantile-onset
      cataracts in humans.

PMID- 30290155
TI  - A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset
      Developmental Epileptic Encephalopathy, Facial Dysmorphism, and Cerebellar
      Dysgenesis.

PMID- 30290156
TI  - A Computational model of the mammalian external tufted cell.
AB  - We introduce a novel detailed conductance-based model of the bursting activity in
      external tufted (ET) cells of the olfactory bulb. We investigate the mechanisms
      underlying their bursting, and make experimentally-testable predictions. The
      ionic currents included in the model are specific to ET cells, and their kinetic
      and other parameters are based on experimental recordings. We validate the model
      by showing that its bursting characteristics under various conditions (e.g.
      blocking various currents) are consistent with experimental observations.
      Further, we identify the bifurcation structure and dynamics that explain bursting
      behavior. This analysis allows us to make predictions of the response of the cell
      to current pulses at different burst phases. We find that depolarizing (but not
      hyperpolarizing) inputs received during the interburst interval can advance burst
      timing, creating the substrate for synchronization by excitatory connections. It
      has been hypothesized that such synchronization among the ET cells within one
      glomerulus might help coordinate the glomerular output. Next we investigate model
      parameter sensitivity and identify parameters that play the most prominent role
      in controlling each burst characteristic, such as the burst frequency and
      duration. Finally, the response of the cell to periodic inputs is examined,
      reflecting the sniffing-modulated input that these cell receive in vivo. We find
      that individual cells can be better entrained by inputs with higher, rather than
      lower, frequencies than the intrinsic bursting frequency of the cell.
      Nevertheless, a heterogeneous population of ET cells (as may be found in a
      glomerulus) is able to produce reliable periodic population responses even at
      lower input frequencies.

PMID- 30290157
TI  - Long non-coding RNA HOXD-AS1 in cancer.
AB  - Cancer is one of the leading causes of death worldwide with a high risk of
      incidence and mortality. Long non-coding RNAs (lncRNAs) have been shown to
      participate in various biological processes, including tumorigenesis and
      progression. The HOXD-AS1 (also known as HAGLR and Mdgt) gene is located between
      the HOXD1 and HOXD3 genes in the HOXD cluster and has been reported to play a
      critical role in the development and progression of cancers. This review
      summarizes the current knowledge on the biological functions and mechanisms of
      HOXD-AS1 in different human cancers, including bladder, cervical, colorectal,
      gastric, ovarian, and prostate cancers, glioma, hepatocellular carcinoma,
      melanoma, osteosarcoma, and non-small cell lung cancer. The aberrant expression
      of HOXD-AS1 in these cancers was related with clinical features of patients with
      cancers. HOXD-AS1 regulates the growth, invasion, and migration of tumor cells
      through different underlying mechanisms. In conclusion, HOXD-AS1 may be
      considered as a promising diagnostic/prognostic biomarker or a novel therapeutic
      target for cancers.

PMID- 30290154
TI  - Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental
      Syndrome.
AB  - Aberrant activation or inhibition of potassium (K+) currents across the plasma
      membrane of cells has been causally linked to altered neurotransmission, cardiac
      arrhythmias, endocrine dysfunction, and (more rarely) perturbed developmental
      processes. The K+ channel subfamily K member 4 (KCNK4), also known as TRAAK (TWIK
      related arachidonic acid-stimulated K+ channel), belongs to the mechano-gated ion
      channels of the TRAAK/TREK subfamily of two-pore-domain (K2P) K+ channels. While
      K2P channels are well known to contribute to the resting membrane potential and
      cellular excitability, their involvement in pathophysiological processes remains
      largely uncharacterized. We report that de novo missense mutations in KCNK4 cause
      a recognizable syndrome with a distinctive facial gestalt, for which we propose
      the acronym FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual
      disability/developmental delay, and gingival overgrowth). Patch-clamp analyses
      documented a significant gain of function of the identified KCNK4 channel mutants
      basally and impaired sensitivity to mechanical stimulation and arachidonic acid.
      Co-expression experiments indicated a dominant behavior of the disease-causing
      mutations. Molecular dynamics simulations consistently indicated that mutations
      favor sealing of the lateral intramembrane fenestration that has been proposed to
      negatively control K+ flow by allowing lipid access to the central cavity of the
      channel. Overall, our findings illustrate the pleiotropic effect of dysregulated
      KCNK4 function and provide support to the hypothesis of a gating mechanism based
      on the lateral fenestrations of K2P channels.

PMID- 30290158
TI  - Discovery of the Long Interspersed Nuclear Element-1 activation product [Open
      Reading Frame-1 (ORF1) protein] in human blood.
AB  - Long Interspersed Nuclear Element 1 is the only autonomous mobile DNA capable of
      self-propagation, and is an environmental biomarker that is activated upon an
      environmental trigger. We have developed an ELISA method to detect and measure
      Open Reading Frame-1 (ORF1) and have applied it to interrogate serum samples from
      men with equivocal prostate specific antigen (PSA) results. Polyclonal antibodies
      were developed using the first 14-amino acid peptide of N-terminal-ORF1 protein.
      Remnant serum samples from a total of 53 men, ages>50 yr, were analyzed for
      immunoreactive ORF1 (iORF1) and PSA concentrations; outcomes for the non-biopsied
      and biopsied groups were also recorded. The dynamic range of the ELISA was
      between (CV): 2.0 (14%) to 30 ng/mL (1.2%). The total imprecision (within
      run/inter-day) was: QC3 = 2.7%/21%, QC6 = 1.1%/18%, and QC20 = 0.33%/11%. The
      median iORF1 concentration in the non-biopsy group was 14.7 ng/mL (Q1 - Q3: 10.5 
      Q3:18.4), which was significantly lower than the Biopsy group at 25.0 ng/mL (Q1 
      Q3: 20.0-33.1), P-value = .003. In conclusion, we have developed a competitive
      ELISA and discovered the presence of iORF1 in serum, which could be used to
      advance future studies involving ORF1 measurement from blood. In addition, iORF1
      may be a complement with the PSA screen to better detect prostate cancer.

PMID- 30290159
TI  - Rapamycin induces the expression of heme oxygenase-1 and peroxyredoxin-1 in
      normal hepatocytes but not in tumorigenic liver cells.
AB  - Rapamycin (sirolimus) is employed as an immunosuppressant following liver
      transplant, to inhibit the re-growth of cancer cells following liver resection
      for hepatocellular carcinoma (HCC), and for the treatment of advanced HCC.
      Rapamycin also induces the expression of antioxidant enzymes in the liver,
      suggesting that pretreatment with the drug could provide a potential strategy to
      reduce ischemia reperfusion injury following liver surgery. The aim of this study
      was to further investigate the actions of rapamycin in inducing expression of the
      antioxidant enzymes heme oxygenase-1 (HO-1) and peroxiredoxin-1 (Prx-1) in normal
      liver and in tumorigenic liver cells. A rat model of segmental hepatic ischemia
      and reperfusion, cultured freshly-isolated rat hepatocytes, and tumorigenic H4IIE
      rat liver cells in culture were employed. Expression of HO-1 and Prx-1 was
      measured using quantitative PCR and western blot. Rapamycin pre-treatment of
      normal liver in vivo or normal hepatocytes in vitro led to a substantial
      induction of mRNA encoding HO-1 and Prx-1. The dose-response curve for the action
      of rapamycin on mRNA expression was biphasic, showing an increase in expression
      at 0 - 0.1 MUM rapamycin but a decrease from maximum at concentrations greater
      than 0.1 MUM. By contrast, in H4IIE cells, rapamycin inhibited the expression of
      HO-1 and Prx-1 mRNA. Oltipraz, an established activator of transcription factor
      Nrf2, caused a large induction of HO-1 and Prx-1 mRNA. The dose response curve
      for the inhibition by rapamycin of HO-1 and Prx-4 mRNA expression, determined in
      the presence of oltipraz, was monophasic with half maximal inhibition at about
      0.01 MUM. It is concluded that, at concentrations comparable to those used
      clinically, pre-treatment of the liver with rapamycin induces the expression of
      HO-1 and Prx-1. However, the actions of rapamycin on the expression of these two
      antioxidant enzymes in normal hepatocytes are complex and, in tumorigenic liver
      cells, differ from those in normal hepatocytes. Further studies are warranted to
      evaluate preconditioning the livers of patients subject to liver resection or
      liver transplant with rapamycin as a viable strategy to reduce IR injury
      following liver surgery.

PMID- 30290160
TI  - Inhibition of catechol-O-methyltransferase in the cynomolgus monkey by opicapone
      after acute and repeated administration.
AB  - INTRODUCTION: The aim of the study was to clarify the dose response for
      inhibition of catechol-O-methyltransferase (COMT) by opicapone, a third
      generation COMT inhibitor, after acute and repeated administration to the
      cynomolgus monkey with pharmacokinetic evaluation at the higher dose. METHODS:
      Three cynomolgus monkeys were used in the study. In the first experiment, COMT
      inhibition was evaluated over 24 h after the first and at 24 h after the last of
      14 daily oral administrations of vehicle, 1, 10 and 100 mg/kg opicapone using a
      crossover design. In the second experiment, the effect of the maximally effective
      dose, 100 mg/kg, was retested under the same conditions with additional
      monitoring of plasma opicapone levels to explore the relationship between
      pharmacokinetics and pharmacodynamics. RESULTS: Opicapone dose-dependently
      inhibited COMT activity, significantly so at 10 and 100 mg/kg. Maximal inhibition
      was 13.1%, 76.4% and 93.2% at 1, 10 and 100 mg/kg respectively, and COMT remained
      significantly inhibited at 24 h after 10 and 100 mg/kg (42.6% and 60.2%
      respectively). Following repeated administration of opicapone residual COMT
      inhibition at 24 h was 15-25% greater at all doses. In contrast to its
      pharmacodynamic effect, opicapone was rapidly absorbed and eliminated, with no
      accumulation in plasma following repeated administration. CONCLUSION: Opicapone
      showed sustained and dose-dependent COMT inhibition despite being rapidly
      eliminated from plasma and with no evidence for accumulation in plasma after 14
      days administration. Opicapone fills the unmet need for a compound with sustained
      COMT inhibition which will improve levodopa bioavailability in patients with
      Parkinson's disease.

PMID- 30290161
TI  - Modelling physical resilience in ageing mice.
AB  - Geroprotectors, a class of drugs targeting multiple deficits occurring with age,
      necessitate the development of new animal models to test their efficacy. The COST
      Action MouseAGE is a European network whose aim is to reach consensus on the
      translational path required for geroprotectors, interventions targeting the
      biology of ageing. In our previous work we identified frailty and loss of
      resilience as a potential target for geroprotectors. Frailty is the result of an
      accumulation of deficits, which occurs with age and reduces the ability to
      respond to adverse events (physical resilience). Modelling frailty and physical
      resilience in mice is challenging for many reasons. There is no consensus on the
      precise definition of frailty and resilience in patients or on how best to
      measure it. This makes it difficult to evaluate available mouse models. In
      addition, the characterization of those models is poor. Here we review potential
      models of physical resilience, focusing on those where there is some evidence
      that the administration of acute stressors requires integrative responses
      involving multiple tissues and where aged mice showed a delayed recovery or a
      worse outcome then young mice in response to the stressor. These models include
      sepsis, trauma, drug- and radiation exposure, kidney and brain ischemia, exposure
      to noise, heat and cold shock.

PMID- 30290162
TI  - The expression of sex steroid receptors and sex steroid-synthesizing/metabolizing
      enzymes in metastasized lymph nodes of prostate Cancer.
AB  - The status of sex steroid receptors and sex steroid-metabolizing enzymes has been
      reported in primary prostate cancer lesions, but that in metastatic lymph nodes
      has remained unknown. Therefore, in this study, we immunolocalized these proteins
      in primary tumors and paired metastatic lymph nodes of prostate cancer and
      correlated the findings with clinicopathologic factors of individual patients.
      The expression status of androgen receptor (AR) and estrogen receptor beta
      (ERbeta) was significantly increased in metastatic lymph nodes compared to
      primary lesions, while that of 17betaHSD1, 17betaHSD2, 17betaHSD5 and STS
      immunoreactivity was decreased in metastatic lymph nodes. In metastatic lymph
      nodes, the status of 5alpha2 was significantly correlated with that of AR. In
      addition, 17betaHSD5, 5alpha1, STS and EST positive cases were significantly
      associated with Gleason score status (GS) (GS>8 vs GS<7) in metastatic lymph
      nodes. Results of our present study did demonstrate that in situ androgen and
      estrogen metabolism and action play roles in pathophysiology of prostate cancer
      in metastatic lymph nodes, but these steroidogenic effects could be different
      from those in primary lesion.

PMID- 30290163
TI  - Ocular surface and chronic pesticide exposure: Evaluating the alterations in
      corneal cellular turnover concerning cell cycle and apoptosis.
AB  - The consequences of chronic pesticide exposure on the ocular surface are not yet
      fully known and lacunae exist regarding the repercussions of this xenobiotic
      insult on cellular turnover. The present work aims to establish the mechanistic
      relationship between ocular morbidity and chronic pesticide exposure by analyzing
      the impact on key regulators responsible for cell cycle and death. Vital
      components of cell cycle and death were primarily explored in this study by
      mimicking the on-field scenario regarding chronic pesticide exposure in a murine
      model. Various cellular aspects were taken into consideration through culture
      analyses, flowcytometric evaluation, fluorescence microscopic studies etc. We
      observed downregulation of key players of the cell-cycle at different stages
      (viz. Cyclin-D1, CDK4, pRb, PCNA, PP1, PP2A, p-cdc 25c and Aurora kinase A) with
      a corresponding increase in the expression of cell-cycle inhibitors like p18 and
      p21, which lead to hypoproliferation of corneal epithelial cells post pesticide
      exposure. The expression of GSK 3beta, a master-molecule involved in both cell
      cycle and apoptotic pathways corresponded well with the scientific theme and
      indicated towards cellular hypoproliferation and increase of apoptosis. Key
      players of both the intrinsic (viz. Bax/Bcl2, JNK) and extrinsic (viz. CD 95)
      apoptotic pathways were found to be activated leading to enhanced cleaved Caspase
      3 expression and corresponding cell death. We tried to highlight the mechanistic
      correlation between the alterations in cellular turnover as the reason behind the
      heightened ocular morbidity due to 'chronic pesticide exposure'- the xenobiotic
      stress exerted by these 'farmers' friends'.

PMID- 30290164
TI  - ERK1/2-mediated EGFR-signaling is required for TGFbeta-induced lens epithelial
      mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) plays a
      critical role in the pathogenesis of fibrotic cataract. Transforming growth
      factor-beta (TGFbeta) is a potent inducer of this fibrotic process in lens.
      Recent studies in cancer progression have shown that in addition to activating
      the canonical Smad signaling pathway, TGFbeta can also transactivate the
      epidermal growth factor receptor (EGFR) to enhance invasive cell migration. The
      present study aims to elucidate the involvement of EGFR-signaling in TGFbeta
      induced EMT in LECs. Treatment with TGFbeta2 induced transdifferentiation of LECs
      into myofibroblastic cells, typical of an EMT. TGFbeta2 induced the
      phosphorylation of the EGFR and upregulation of Egfr and Hb-egf gene expression.
      Pharmacologic inhibition of EGFR-signaling using PD153035 inhibited TGFbeta
      induced EMT, including the upregulation of mesenchymal markers and downregulation
      of epithelial markers. Crosstalk between TGFbeta2-induced EGFR and ERK1/2 was
      evident, with both pathways impacting on Smad2/3-signaling. Our finding that
      TGFbeta2 transactivates downstream EGFR-signaling reveals a previously unknown
      mechanism in the pathogenesis of cataract. Understanding the complex interplay
      between divergent canonical and non-canonical signaling pathways, as well as
      downstream target genes involved in TGFbeta-induced EMT, will enable the
      development of more effective targeted therapies in the pharmacological treatment
      of cataract.

PMID- 30290165
TI  - Spred negatively regulates lens growth by modulating epithelial cell
      proliferation and fiber differentiation.
AB  - Spred, like Sprouty (Spry) and also Sef proteins, have been identified as
      important regulators of receptor tyrosine kinase (RTK)-mediated MAPK/ERK
      signaling in various developmental systems, controlling cellular processes such
      as proliferation, migration and differentiation. Spreds are widely expressed
      during early embryogenesis, and in the eye lens, become more localised in the
      lens epithelium with later development, overlapping with other antagonists
      including Spry. Given the synexpression of Spreds and Spry in lens, in order to
      gain a better understanding of their specific roles in regulating growth factor
      mediated-signaling and cell behavior, we established and characterised lines of
      transgenic mice overexpressing Spred1 or Spred2, specifically in the lens. This
      overexpression of Spreds resulted in a small lens phenotype during ocular
      morphogenesis, retarding its growth by compromising epithelial cell proliferation
      and fiber differentiation. These in situ findings were shown to be dependent on
      the ability of Spreds to suppress MAPK-signaling, in particular FGF-induced
      ERK1/2-signaling in lens cells. This was validated in vitro using lens epithelial
      explants, that highlighted the overlapping role of Spreds with Spry2, but not
      Spry1. This study provides insights into the putative function of Spreds and Spry
      in situ, some overlapping and some distinct, and their importance in regulating
      lens cell proliferation and fiber differentiation contributing to lens and eye
      growth.

PMID- 30290166
TI  - Deoxynivalenol induces toxicity and apoptosis in piglet hippocampal nerve cells
      via the MAPK signaling pathway.
AB  - Deoxynivalenol (DON) is a mycotoxin capable of producing a variety of toxic
      effects in human and animals. In this study, the effect of DON treatment on
      cytotoxicity and apoptotic pathways in piglet hippocampal nerve cells (PHNCs) was
      determined. The effects of DON on cellular morphology, cell activity, lactate
      dehydrogenase (LDH) release, the protein expression of mitogen-activated protein
      kinase (MAPK) pathway, and the relative expression of key genes related to
      apoptosis were evaluated. The results indicated that DON significantly inhibited
      cellular viability and promoted the release of LDH by damaging the membrane
      integrity of PHNCs, however, the cellular viability was increased and LDH leakage
      rate were decreased after adding MAPK inhibitors. DON induced PHNCs apoptosis and
      phosphorylation of MAPK pathway proteins dose-dependently. The ratios of phospho
      p-JNK/JNK and p-p38/p38 significantly increased with the increase of DON
      concentration, while the p-ERK/ERK ratio significantly decreased. In addition,
      DON upregulated the BAX mRNA level, and downregulated the BCL2 mRNA level. Pre
      incubation with inhibitors of JNK (SP600125) and p38 (SB202190) significantly
      decreases the BAX/BCL2 ratio. However, pre-incubation with the inhibitor of ERK
      (U0126), significantly increased the BAX/BCL2 ratio. These data demonstrated that
      DON induces toxic effects and apoptosis in PHNCs via the MAPK signaling pathway.

PMID- 30290167
TI  - Inducible SHP-2 activation confers resistance to imatinib in drug-tolerant
      chronic myeloid leukemia cells.
AB  - BCR-ABL kinase mutations, accounting for clinical resistance to tyrosine kinase
      inhibitor (TKI) such as imatinib, frequently occur in acquired resistance or in
      advanced phases of chronic myeloid leukemia (CML). Emerging evidence implicates a
      critical role for non-mutational drug resistance mechanisms underlying the
      survival of residual cancer 'persister' cells. Here, we utilized non-mutational
      imatinib-resistant K562/G cells to reveal SHP-2 as a resistance modulator of
      imatinib treatment response during the early phase. SHP-2 phosphorylation was
      significantly higher in K562/G cells than in sensitive K562 cells. In K562 cells,
      both short-term and long-term exposure to imatinib induced SHP-2 phosphorylation.
      Consistently, gain- and loss-of-function mutants in SHP-2 proved its regulation
      of imatinib resistance. SHP-2 inhibitor and imatinib exhibited a strong antitumor
      synergy in in vitro and in vivo K562/G models. Mechanistically, dual SHP-2 and
      BCR-ABL inhibition blocked RAF/MEK/ERK and PI3K/AKT/mTOR pathways, respectively,
      leading to dramatic apoptotic death of K562/G cells. In conclusion, our results
      highlight that SHP-2 could be exploited as a biomarker and therapeutic target
      during the early phase of imatinib resistance development in CML.

PMID- 30290168
TI  - Metformin attenuates cardiovascular and renal injury in uninephrectomized rats on
      DOCA-salt: Involvement of AMPK and miRNAs in cardioprotection.
AB  - Hypertension is associated with major cardiovascular (CV) and renal
      complications. The molecular intricacy by which hypertension leads to end organ
      damage is not known. To address this, we aimed to determine the effect of
      deoxycorticosterone acetate (DOCA) -salt (sodium chloride)-induced hypertension
      on the alterations in renin-angiotensin system, leading to CV and renal
      dysfunction in uninephrectomized male Sprague Dawley rats. MicroRNAs involved in
      this were also not yet explored. Metformin was used to delineate the role of AMPK
      in mitigating the hypertension-induced CV and renal dysfunction. Administering
      DOCA and offering saline to uninephrectomized rats, induced hypertension and
      associated abnormalities of diastolic dysfunction, CV and renal hypertrophy and
      fibrosis via activating local renin angiotensin system. Western blotting and RT
      qPCR analysis of diseased heart revealed decreased SERCA2, p-AMPK, miR-146a, miR
      99b and increased miR-155 and metformin administered, at dose of 300 mg/kg/day,
      for a period of 8 weeks prevented CV and renal damage. To our knowledge, we are
      the first to show that involvement of epigenetic alterations at microRNA level
      might be responsible for hypertension-induced cardiac dysfunction and metformin
      reverses these alterations.

PMID- 30290169
TI  - Salinomycin ameliorates oxidative hepatic damage through AMP-activated protein
      kinase, facilitating autophagy.
AB  - Salinomycin, a monocarboxylic ionophore in Streptomyces albus, has been studied
      as an anti-cancer agent. However, we wondered whether salinomycin has another
      effect such as an anti-oxidant and hepatic protectant, because some chemical
      drugs treating human diseases were sometimes related with their toxic effects.
      Therefore, this study was conducted to examine the effects of salinomycin against
      oxidative stress and mitochondrial impairment in vivo and in vitro as well as the
      cellular mechanisms of action. In hepatocyte, salinomycin inhibited arachidonic
      acid (AA) + iron-induced apoptosis, mitochondrial dysfunction and ROS production.
      As a molecular mechanism, salinomycin induced autophagy through AMP-activated
      protein kinase (AMPK) activation, as assessed by the accumulation of acidic
      vesicle organelles, p62 and LC3-II. Moreover, these protective effects were
      blocked by AMPK inhibition, which indicates the importance of AMPK in the process
      of salinomycin's effects. In mice, oral administration of salinomycin protected
      against carbon tetrachloride (CCl4)-induced oxidative stress and liver injury,
      and also activated AMPK as well as autophagy-related proteins in the liver.
      Collectively, salinomycin had the ability to protect hepatocytes against AA+iron
      induced reactive oxygen species production and mitochondrial dysfunction, as well
      as CCl4-induced liver injury. Although this beneficial effect was demonstrated
      under severe oxidative stress, this study showed that salinomycin protected the
      liver against the oxidative stress and liver damage through AMPK and autophagy,
      and suggest that salinomycin has a possibility to treat a broad range of
      diseases.

PMID- 30290170
TI  - Won't You Be My Neighbor? Muscle Stem Cells Recruit Endothelial Cells to Their
      Niche.
AB  - The maintenance of a pool of quiescent satellite cells (muscle stem cells) is
      necessary for long-term muscle health. In this issue of Cell Stem Cell, Verma et
      al. (2018) show that satellite cells recruit endothelial cells to create a
      vascular niche and that cross-talk between endothelial and satellite cells is
      vital for replenishment and maintenance of quiescent satellite cells.

PMID- 30290171
TI  - Hox in the Niche Controls Hairy-geneity.
AB  - Patterns of mammalian hair growth vary in different regions of the body, but the
      mechanisms controlling this heterogeneity are unclear. In this issue of Cell Stem
      Cell, Yu et al. (2018) show that Hoxc gene expression in hair follicle mesenchyme
      varies along the anterior-posterior body axis and contributes to regional
      differences in hair growth.

PMID- 30290172
TI  - Hematopoietic Stem Cells Rock Around The Clock: Circadian Fate Control via
      TNF/ROS Signals.
AB  - Hematopoietic stem cell function is closely tied to circadian rhythms. In this
      issue of Cell Stem Cell, Golan et al. (2018) identify crosstalk between circadian
      hormone signals, the inflammatory cytokine TNF, and bone marrow macrophages as a
      key regulator of HSC proliferation, differentiation, and self-renewal in the bone
      marrow.

PMID- 30290173
TI  - 3D Human Esophageal Epithelium Steps Out from hPSCs.
AB  - Human pluripotent stem cell (hPSC)-derived organoids can reveal important
      principles underlying tissue development. In this issue of Cell Stem Cell, Zhang
      et al. (2018) and Trisno et al. (2018) establish protocols for generating
      esophageal epithelial cells and 3D stratified epithelium from hPSCs, revealing
      roles for key signaling pathways and how they are controlled by critical
      transcription factors.

PMID- 30290174
TI  - Human Skeletal Stem Cells: The Markers Provide Some Clues in the Hunt for Hidden
      Treasure.
AB  - Little is known about skeletal stem cell populations in vivo. Recently in Cell,
      Chan et al. (2018) identified a human skeletal stem cell population that can be
      isolated from multiple human bone locations and is capable of self-renewal and
      differentiation into bone, cartilage, and stroma, but not fat.

PMID- 30290175
TI  - New Recipes for Myelinating Oligodendrocytes.
AB  - While myelinating oligodendrocytes are attractive candidates for cell-based
      regenerative therapies, producing them in adequate quantities and regulation of
      progenitor differentiation pathways has proven limiting. Recently, Hubler et al.
      (2018) and Madhavan et al. (2018) generated cerebral organoids with myelinating
      oligodendrocytes and manipulated sterol pathway small molecules to promote myelin
      synthesis.

PMID- 30290176
TI  - Taking on the Elephant in the Tissue Culture Room: iPSC Modeling for Sporadic
      ALS.
AB  - Modeling ALS remains a major challenge since the vast majority of cases are
      sporadic. Recently in Nature Medicine, Fujimori et al. leverage genetic
      heterogeneity and define subgroups of iPSC-derived motor neurons using multiplex
      phenotypic profiles, and thus make substantial progress toward robust modeling of
      both familial and sporadic ALS.

PMID- 30290178
TI  - Stage-Specific Transcription Factors Drive Astrogliogenesis by Remodeling Gene
      Regulatory Landscapes.
AB  - A broad molecular framework of how neural stem cells are specified toward
      astrocyte fate during brain development has proven elusive. Here we perform
      comprehensive and integrated transcriptomic and epigenomic analyses to delineate
      gene regulatory programs that drive the developmental trajectory from mouse
      embryonic stem cells to astrocytes. We report molecularly distinct phases of
      astrogliogenesis that exhibit stage- and lineage-specific transcriptomic and
      epigenetic signatures with unique primed and active chromatin regions, thereby
      revealing regulatory elements and transcriptional programs underlying astrocyte
      generation and maturation. By searching for transcription factors that function
      at these elements, we identified NFIA and ATF3 as drivers of astrocyte
      differentiation from neural precursor cells while RUNX2 promotes astrocyte
      maturation. These transcription factors facilitate stage-specific gene expression
      programs by switching the chromatin state of their target regulatory elements
      from primed to active. Altogether, these findings provide integrated insights
      into the genetic and epigenetic mechanisms steering the trajectory of
      astrogliogenesis.

PMID- 30290177
TI  - Muscle Satellite Cell Cross-Talk with a Vascular Niche Maintains Quiescence via
      VEGF and Notch Signaling.
AB  - Skeletal muscle is a complex tissue containing tissue resident muscle stem cells
      (satellite cells) (MuSCs) important for postnatal muscle growth and regeneration.
      Quantitative analysis of the biological function of MuSCs and the molecular
      pathways responsible for a potential juxtavascular niche for MuSCs is currently
      lacking. We utilized fluorescent reporter mice and muscle tissue clearing to
      investigate the proximity of MuSCs to capillaries in 3 dimensions. We show that
      MuSCs express abundant VEGFA, which recruits endothelial cells (ECs) in vitro,
      whereas blocking VEGFA using both a vascular endothelial growth factor (VEGF)
      inhibitor and MuSC-specific VEGFA gene deletion reduces the proximity of MuSCs to
      capillaries. Importantly, this proximity to the blood vessels was associated with
      MuSC self-renewal in which the EC-derived Notch ligand Dll4 induces quiescence in
      MuSCs. We hypothesize that MuSCs recruit capillary ECs via VEGFA, and in return,
      ECs maintain MuSC quiescence though Dll4.

PMID- 30290180
TI  - Modulation of male mouse sociosexual and anxiety-like behaviors by vasopressin
      receptors.
AB  - Although the involvement of two types of vasopressin (AVP) receptors, v1a and
      v1b, in neural regulation of social behavior is well documented in rodents, there
      is no report on combined actions of them in regulation of social behavior. In
      this study, we investigated behavioral differences between wild-type (WT) and v1a
      and v1b double knockout (dKO) mice. For this, we measured olfactory preference,
      sexual behavior with receptive females (four weekly tests) in an enriched large
      observation cage, and anxiety-like behaviors. No difference between WT and dKO
      mice was found in olfactory preferences for estrous female odor to male odor.
      Over all four mating tests, the number of mounts and pursuits after receptive
      females was significantly greater in dKO mice than in WT mice. In the elevated
      plus maze and the open field test, dKO mice showed lower anxiety-like behavior
      than WT mice. Finally, we measured approach behavior to several types of objects,
      figurines, and caged anestrous or estrous females placed in the open field
      apparatus. The only difference observed was that dKO mice spent longer in the
      vicinity of estrous females than did WT mice. These findings suggest that
      vasopressin receptors are involved in the regulation of sociosexual behavior,
      presumably partly mediated by emotional responses, in male mice.

PMID- 30290181
TI  - Sexually experienced, but not naive, female rats show a conditioned object
      preference (COP) for mating after a single training trial.
AB  - Female rats with mating experience spend more time with the male rat, exhibit
      shorter contact-return latency to intromission, and display more proceptive
      behaviors in the male rat's compartment than during the first mating experience.
      The present study tested 1) whether mating induced conditioned object preference
      (COP) is possible with a single conditioning trial and 2) whether a preference is
      induced for an object associated with the first mating encounter or the fifth
      mating encounter in female rats. Ovariectomized, Long-Evans female rats were
      primed with estradiol benzoate + progesterone and either exposed to an empty
      paced mating chamber for 15 min (Naive) or received a 15 intromission test of
      paced mating behavior (Experienced) on four separate occasions before undergoing
      the COP procedure. Experienced, but not Naive, female rats developed a COP for a
      single mating bout, indicating that mating is highly rewarding for sexually
      experienced female rats. The findings raise questions about the effect of sexual
      experience on reward regions in the brain, the responsiveness of genital tissue,
      and learning mechanisms.

PMID- 30290179
TI  - Single-Cell Transcriptomic Analysis of Cardiac Differentiation from Human PSCs
      Reveals HOPX-Dependent Cardiomyocyte Maturation.
AB  - Cardiac differentiation of human pluripotent stem cells (hPSCs) requires
      orchestration of dynamic gene regulatory networks during stepwise fate
      transitions but often generates immature cell types that do not fully
      recapitulate properties of their adult counterparts, suggesting incomplete
      activation of key transcriptional networks. We performed extensive single-cell
      transcriptomic analyses to map fate choices and gene expression programs during
      cardiac differentiation of hPSCs and identified strategies to improve in vitro
      cardiomyocyte differentiation. Utilizing genetic gain- and loss-of-function
      approaches, we found that hypertrophic signaling is not effectively activated
      during monolayer-based cardiac differentiation, thereby preventing expression of
      HOPX and its activation of downstream genes that govern late stages of
      cardiomyocyte maturation. This study therefore provides a key transcriptional
      roadmap of in vitro cardiac differentiation at single-cell resolution, revealing
      fundamental mechanisms underlying heart development and differentiation of hPSC
      derived cardiomyocytes.

PMID- 30290182
TI  - Sick and grumpy: Changes in social behaviour after a controlled immune
      stimulation in group-housed gilts.
AB  - Poor health is associated with an increased risk of tail biting outbreaks in
      pigs. We propose that this is because illness changes social dynamics either by
      changing the behaviour of the sick pig towards its penmates, the behaviour of the
      healthy penmates towards the sick pig, or both. We tested the effect of immune
      stimulation (lipopolysaccharide (LPS) injection: O111:B4; 1.5 MUg kg-1 IV) on
      social behaviour in gilts housed in triplets in a cross-over experiment. Each pen
      was subjected to the control treatment (all three pigs injected with saline) and
      then LPS treatment (one pig injected with LPS, two injected with saline), or vice
      versa. LPS injected pigs had a shift in social motivation and performed more tail
      and ear- directed behaviour than saline pigs two days after injection. They
      seemed to fit the description of 'sick and grumpy'. This change was seen about 40
      h after the signs of acute illness dissipated and was not accompanied by a
      similar increase in activity. We discuss possible mechanisms for this behavioural
      change in light of changes in neurotransmitter levels at three days after LPS
      injection described in a previous experiment.

PMID- 30290183
TI  - Cryptochrome 1 promotes osteogenic differentiation of human osteoblastic cells
      via Wnt/beta-Catenin signaling.
AB  - AIMS: The exact mechanism underlying osteoblast differentiation and proliferation
      remains to be further elucidated. The circadian clock has been universally
      acknowledged controls behavioral activities and biological process in mammals.
      Cryptochrome 1 (Cry1), one of the core circadian genes, is associated with bone
      metabolism. However, the exact role and potential mechanism of Cry1 in regulating
      osteogenesis are still unclear. MAIN METHODS: Western blotting and qRT-PCR were
      applied to detect Cry1 expression levels, molecules in osteogenesis related
      signaling pathways and osteogenic transcriptional markers. The ALP staining and
      Alizarin red S staining were performed to weigh osteogenic state, while CCK8
      assay was used to detect cell growth rates. Osteogenic capability of osteoblasts
      was determined using an ectopic bone formation assay. KEY FINDINGS: Cry1 was
      upregulated in the process of osteoblast differentiation, along with osteogenic
      transcriptional factors. Then, Cry1 upregulation and knockdown cell lines were
      established and we found Cry1 overexpression promoted osteogenesis and
      proliferation of osteoblasts both in vitro and in vivo. Besides, the canonical
      Wnt/beta-Catenin signaling was increasingly activated by Cry1 overexpression,
      whereas inhibition of beta-Catenin restrained enhanced osteogenic capability of
      Cry1 upregulated osteoblasts. SIGNIFICANCE: In conclusion, these results suggest
      that Cry1 promotes osteogenic differentiation of human osteoblasts through the
      canonical Wnt/beta-Catenin signaling.

PMID- 30290184
TI  - Alternative mechanisms of translation initiation: An emerging dynamic regulator
      of the proteome in health and disease.
AB  - Eukaryotic mRNAs were historically thought to rely exclusively on recognition and
      binding of their 5' cap by initiation factors to effect protein translation.
      While internal ribosome entry sites (IRESs) are well accepted as necessary for
      the cap-independent translation of many viral genomes, there is now recognition
      that eukaryotic mRNAs also undergo non-canonical modes of translation initiation.
      Recently, high-throughput assays have identified thousands of mammalian
      transcripts with translation initiation occurring at non-canonical start codons,
      upstream of and within protein coding regions. In addition to IRES-mediated
      events, regulatory mechanisms of translation initiation have been described
      involving alternate 5' cap recognition, mRNA sequence elements, and ribosome
      selection. These mechanisms ensure translation of specific mRNAs under conditions
      where cap-dependent translation is shut down and contribute to pathological
      states including cardiac hypertrophy and cancer. Such global and gene-specific
      dynamic regulation of translation presents us with an increasing number of novel
      therapeutic targets. While these newly discovered modes of translation initiation
      have been largely studied in isolation, it is likely that several act on the same
      mRNA and exquisite coordination is necessary to maintain 'normal' translation. In
      this short review, we summarize the current state of knowledge of these
      alternative mechanisms of eukaryotic protein translation, their contribution to
      normal and pathological cell biology, and the potential of targeting translation
      initiation therapeutically in human disease.

PMID- 30290185
TI  - Application of induced pluripotent stem cell transplants: Autologous or
      allogeneic?
AB  - The development of induced pluripotent stem cells (iPS cells) has raised the
      prospect of patient-specific treatments for various diseases. Theoretically, iPS
      cell technology avoids the limitations of human embryonic stem cells (ES cells),
      including poor establishment, ethical issues, and immune rejection of allogeneic
      transplantation. However, the immunogenicity of iPS cells has attracted the
      attention of researchers, and it remains unclear whether iPS cells and their
      derivatives will be recognized as a patient's own cells. Even though iPS-derived
      functional cells have been used in the treatment of some diseases, the process of
      somatic cell reprogramming and iPS cell differentiation is time-consuming, making
      it difficult to use iPS cells in acute illness or injury. In recent years, it has
      been suggested that iPS cells may be used as allografts by establishing an iPS
      cell bank and HLA matching, providing a novel strategy for the clinical
      application of iPS cells. This article provides a concise overview of iPS cell
      immunogenicity, and summarizes published data regarding the application of iPS
      cells in both autologous and allogeneic transplantation in order to help develop
      more reliable biotechnical strategies utilizing iPS cells.

PMID- 30290186
TI  - Bone health consequence of adjuvant Anastrozole in monotherapy or associated with
      biochanin-A in ovariectomized rat model.
AB  - AIMS: We investigate the consequence of adjuvant anastrozole (ANA) in monotherapy
      or associated with biochanin A (BCA) in ovariectomized (OVX) rat model and the
      degree of developing bone loss in both conditions. MATERIALS AND METHODS: Sixty
      female rats were assigned to six groups. Five groups were bilaterally OVX, and
      one was sham operated. The five groups were; ANA group (0.5 mg/kg b.wt orally),
      BCA (5 mg/kg b.wt intraperitoneally (I/P), co-treated group (BCA + ANA), two
      control groups receiving even distilled water orally or DMSO I/P for twenty
      weeks. Bone turnover biomarkers BALP, OC, PTH, TRAP and TNFalpha were determined
      in serum. Bone mineral content, histological and morphometric measurements on rat
      femurs were performed. BMD by X-ray technique on tibias of rats and CT analysis
      of lumbar vertebrae of all treated and sham groups were applied. KEY FINDINGS:
      There was marked elevation in bone turnover biomarkers with high serum Ca and P
      content in the ANA-treated rats. Moreover marked elevation of TNFalpha, PTH, TC
      and TG, ANA caused severe changes in the BMD detected by X-ray in tibial bones
      and CT analysis of lumbar vertebrae of OVX rats. While I/P injection of BCA
      ameliorated the adverse bone health decrements caused by ANA. SIGNIFICANCE: The
      study highlights the importance of the BCA supplementation in accordance with the
      ANA therapy in case of ovariectomized rat model of osteoporosis which is
      clinically presented in Postmenopausal women with breast cancer during which
      considerable risk of developing osteoporosis is predicted during treatment.

PMID- 30290187
TI  - Updated review of current pharmacological and non-pharmacological management of
      irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal
      tract that is usually associated with chronic abdominal pain and altered bowel
      habits. The two spectra of the disease include constipation-predominant IBS and
      Diarrhea-predominant IBS. Earlier it was thought to be an unexplained brain-gut
      disorder, but of late, various underlying causes suggesting primary gut
      disturbance have been identified. The initial management primarily includes the
      non-pharmacological measures such as dietary modifications, increasing physical
      activity, and psychological therapy. Pharmacological management is adjunct to non
      pharmacological management, and the drug is chosen based on the predominant
      symptom of bowel habit whether constipation or diarrhea. In this review, we aim
      to update the readers on the currently available management options in the
      treatment of IBS - both pharmacological and non-pharmacological options. Further,
      for the various pharmacological treatments, we summarize the clinical
      pharmacology, indications, contraindications, adverse effects and use in
      pregnancy.

PMID- 30290188
TI  - Cannabinoids in depressive disorders.
AB  - Cannabis sativa is one of the most popular recreational and medicinal plants.
      Benefits from use of cannabinoid agents in epilepsy, multiple sclerosis,
      Parkinson's disease, Alzheimer's disease, and others have been suggested. It
      seems that the endocannabinoid system is also involved in the pathogenesis and
      treatment of depression, though its role in this mental disease has not been
      fully understood yet. Both the pro- and antidepressant activity have been
      reported after cannabis consumption and a number of pre-clinical studies have
      demonstrated that both agonist and antagonist of the endocannabinoid receptors
      act similarly to antidepressants. Responses to the cannabinoid agents are
      relatively fast, and most probably, the noradrenergic, serotoninergic,
      glutamatergic neurotransmission, neuroprotective activity, as well as modulation
      of the hypothalamic-pituitary-adrenal axis are implicated in the observed
      effects. Based on the published data, the endocannabinoid system evidently gives
      novel ideas and options in the field of antidepressant treatment, however further
      studies are needed to determine which group of patients could benefit from this
      type of therapy.

PMID- 30290189
TI  - Without Warning: Scleroderma Renal Crisis.

PMID- 30290190
TI  - Follow the Beads: Fibromuscular Dysplasia.

PMID- 30290191
TI  - Corticosteroids in the Management of Severe Coccidioidomycosis.
AB  - BACKGROUND: There is limited data suggesting that recovery from severe pulmonary
      infection with Coccidioides may be hastened by the addition of systemic
      corticosteroids. METHODS: We present a case report of 2 patients with persistent
      and progressive coccidioidomycosis who demonstrated a dramatic response to
      adjunctive corticosteroid therapy. RESULTS: Both patients had Coccidioides
      immitis cultured from respiratory samples. One was a 69-year-old man who had been
      treated with combination fluconazole and liposomal amphotericin for over 6 weeks,
      with persistent fever and pneumonia. The other was a 61-year-old man treated with
      fluconazole and then amphotericin for 3 weeks, with progression to acute
      respiratory distress syndrome and shock. Both received short courses of
      intravenous methylprednisolone and recovered to be discharged home. CONCLUSIONS:
      As opposed to associated hypersensitivity, corticosteroid treatment in these
      cases was directed at modulating the ongoing destructive effects of unchecked
      inflammation. Rapid improvement was noted in both cases and raises the
      possibility that the addition of systemic corticosteroids may hasten recovery in
      patients with severe coccidioidomycosis.

PMID- 30290192
TI  - Inferior Vena Cava Filters in Patients with Recurrent Pulmonary Embolism.
AB  - BACKGROUND: There are sparse data to support the recommendation for inferior vena
      cava (IVC) filters in patients with recurrent pulmonary embolism while on
      anticoagulant therapy. METHODS: This was a retrospective cohort study of
      administrative data from the Premier Healthcare Database, 2009-2014. All-cause
      mortality according to the use of IVC filters was evaluated in patients who
      suffered a recurrent pulmonary embolism within 3 months of an index pulmonary
      embolism. Patients were identified by International Classification of Disease,
      9th Clinical Modification codes. A time-dependent analysis controlled for
      immortal time bias. RESULTS: An IVC filter was inserted in 603 of 814 (74.1%) of
      patients hospitalized for recurrent pulmonary embolism within 3 months of an
      index pulmonary embolism. Mortality with an IVC filter was 18 of 603 (3.0%) vs 83
      of 211 (39.3%) (P < .0001) without a filter. Among patients with recurrent
      pulmonary embolism who were stable and did not receive thrombolytic therapy or
      undergo pulmonary embolectomy, mortality with an IVC filter was 15 of 572 (2.6%)
      vs 72 of 169 (42.6%) (P < .0001) without a filter. CONCLUSION: In the United
      States, usual practice was to insert an IVC filter in patients with early
      recurrent pulmonary embolism. Mortality was lower in those who received an IVC
      filter. Even stable patients with early recurrent pulmonary embolism showed a
      decreased mortality with IVC filters, even though in other circumstances, IVC
      filters do not reduce mortality in stable patients. Additional cohort studies
      would be useful in the absence of a randomized controlled trial.

PMID- 30290193
TI  - Variation in the Use of Warfarin and Direct Oral Anticoagulants in Atrial
      Fibrillation and Associated Cost Implications.
AB  - BACKGROUND: Little is known about national patterns of anticoagulant use among
      patients with atrial fibrillation after the availability of direct oral
      anticoagulants (DOACs) and the associated implications for healthcare spending.
      METHODS: The Medical Expenditure Panel Survey, a nationally representative
      survey, collects detailed information about prescription drug use, cost, and
      medical diagnoses. Using International Classification of Disease Ninth Edition
      (ICD-9) codes and self-reporting, adults with atrial fibrillation were estimated
      between 2010 and 2014. We examined proportions of patients receiving warfarin and
      DOACs overall and across sociodemographic and clinical groups. Total drug
      expenditures and out-of-pocket spending were calculated adjusting to 2014 US
      dollars. RESULTS: The study population ranged from 364 (equivalent to 4.7
      million) in 2010 to 409 (equivalent to 5.5 million) in 2014. Overall use of any
      anticoagulant increased from 32.4% to 40.1%. DOAC use increased from 0.56% to
      17.2%, and warfarin use declined from 32.8% to 22.9% (p trend < 0.01). This trend
      was seen in nearly all subgroups evaluated. Estimated prescription drug spending
      on DOACs and warfarin during this time rose from $330 million to $1.9 billion.
      Out-of-pocket costs for DOACs increased from $10 million to $218 million.
      CONCLUSION: In a large, nationwide cohort of adults with atrial fibrillation, we
      observed a rapid increase in the use of DOACs, significant disparities in
      medication use based on sociodemographic and clinical factors, and an increase in
      overall and out-of-pocket costs for anticoagulants corresponding to the increased
      use of DOACs. These patterns have important implications for healthcare quality,
      equity, and spending.

PMID- 30290194
TI  - Bacteriophage T7 transcription system: an enabling tool in synthetic biology.
AB  - Since its discovery in the 1970s, the T7 RNA polymerase (T7 RNAP) transcription
      system has been applied extensively as an effective tool in molecular biology
      because of its robust function in various hosts, including prokaryotic,
      eukaryotic and cell free systems. Recently, the T7 RNAP transcription system has
      emerged as a critical component for synthetic biology. The present paper
      summarizes the advances of the T7 RNAP transcription system in synthetic biology,
      including the recent progress of T7 RNAP structure and its cognate promoter and
      terminator and its application in cell free systems, logic gates and orthogonal
      genetic circuits.

PMID- 30290195
TI  - Biological impacts of organophosphates chlorpyrifos and diazinon on development,
      mitochondrial bioenergetics, and locomotor activity in zebrafish (Danio rerio).
AB  - The objectives of this study were to compare the biological responses in
      developing zebrafish to two organophosphate insecticides, chlorpyrifos (CPF) and
      diazinon (DZN). Zebrafish embryos were exposed to either solvent control (0.1%
      DMSO, v/v), or one dose of 0.1, 1.0, 10.0 and 25.0 MUM CPF, as well as one dose
      of 0.1, 1.0, 10.0 and 100.0 MUM DZN for 96 h. CPF at 10.0 and 25.0 MUM caused 70
      80% and 100% mortality in embryos after 96 h exposure, whereas embryos treated
      with 10.0 and 100.0 MUM DZN showed 30-40% and 70-80% lethality. CPF at 10.0 MUM
      significantly decreased cumulative hatching rate, whereas hatching rate was
      significantly reduced in embryos treated with 100.0 MUM DZN. Spinal lordosis was
      primarily observed in larvae exposed to 1.0 and 10.0 MUM CPF, whereas pericardial
      edema was mainly detected with 10.0 and 100.0 MUM DZN exposure. Embryo exposed to
      1.0, 10.0 and 25.0 MUM CPF exhibited no mitochondrial dysfunction; exposure to
      100.0 MUM DZN significantly inhibited mitochondrial bioenergetics. To determine
      if CPF and DZN affected larval activity, dark photokinesis response was assessed
      in larvae following 7 days exposure to 0.1 and 1.0 MUM CPF, as well as to 0.1
      1.0, and 10.0 MUM DZN. Larvae exposed to 1.0 MUM CPF showed hypoactivity, whereas
      the activity in the dark was not overtly changed in larvae exposed to DZN. In
      summary, CPF showed higher developmental toxicity compared to DZN. Moreover,
      based on the types of morphological deformities noted, as well as differences in
      locomotor activity, we conclude that OPs have unique chemical-specific modes of
      action that can result in varied biological responses during early development.

PMID- 30290196
TI  - Nasal immunization with RSV F and G protein fragments conjugated to an M cell
      targeting ligand induces an enhanced immune response and protection against RSV
      infection.
AB  - Human respiratory syncytial virus (RSV) is a major paediatric health concern
      worldwide. The development of an effective and safe vaccine against RSV is
      urgently needed. As RSV infects via the mucosal surfaces, developing a nasal
      vaccine may offer protective benefits over alternative administration routes. In
      this study, we tested a recombinant protein FG-Gb1 as an intranasal vaccine
      candidate against RSV. FG-Gb1 consists of the core fragments of the RSV fusion
      (F) and attachment (G) proteins conjugated to an microfold (M) cell-specific
      ligand Gb-1. Intranasal immunization with FG-Gb1 induced efficient systemic and
      mucosal immune responses as measured by the level of antigen-specific antibodies,
      cytokine-secreting cells and antigen-specific lymphocyte proliferation after
      exposure to antigen. Moreover, intranasal immunization induced protective
      immunity against nasal challenge with RSV, which was confirmed by a lack of
      weight loss and by viral clearance after challenge. Collectively, we confirmed
      that a ligand capable of targeting the conjugated antigen to nasopharynx
      associated lymphoid tissue (NALT) can be used as an effective nasal vaccine
      adjuvant to induce protective immunity against RSV infection. Moreover, FG-Gb1
      may have promise as an RSV vaccine but requires further studies.

PMID- 30290197
TI  - Fluoxetine can inhibit coxsackievirus-B4 E2 in vitro and in vivo.
AB  - Group B Coxsackieviruses (CV-B) are responsible for various acute human diseases,
      and they are involved in chronic diseases such as type 1 diabetes. It has been
      reported that fluoxetine (FLX) inhibited CV-B4E2 in human cell lines in vitro. In
      so far as CV-B4E2 can replicate in CD1 mice, it was investigated whether FLX
      could inhibit CV-B4E2 in vitro and in vivo in mouse systems. When 5.5 MUM FLX was
      added to CV-B4E2-infected Min-6 cell (murine pancreas beta cell line) cultures,
      the virus-induced cytopathic effect was inhibited. In this system and in CV-B4E2
      infected CD1 mouse pancreatic organotypic cultures treated with FLX the levels of
      infectious particles in supernatant fluids were below the limit of detection of
      the assay. The administration of FLX (10 mg/kg/day) by intraperitoneal route
      resulted in significant reduced levels of infectious particles in heart and
      pancreas of mice inoculated with CV-B4E2 by the same route. In conclusion FLX can
      inhibit CV-B4 in vitro and in vivo in mouse systems, additional studies are
      needed to investigate further the potential value of FLX to combat CV-B4
      infections and to treat CV-B4-induced diseases.

PMID- 30290198
TI  - The relationship between naturalistic sleep variation and error monitoring in
      young adults: An event-related potential (ERP) study.
AB  - Sleep deprivation studies have highlighted the importance of adequate sleep for
      optimal daytime functioning. However, there is limited research exploring whether
      variations in natural sleep patterns produce similar difficulties to those seen
      in sleep deprivation studies. The aim of the current study was to explore whether
      naturalistic reductions in sleep duration and/or sleep quality were associated
      with behavioural and electrophysiological measures of cognitive control. Sixty
      undergraduate students were asked to wear an actigraph for 7 consecutive nights
      before completing a hybrid Flanker-Go/NoGo task whilst continuous EEG data were
      recorded. Participants were assigned to high or low sleep quality and short or
      long sleep duration groups using the National Sleep Foundation guidelines.
      Results indicated that individuals who, on average, slept <7 h each night showed
      inefficiencies in error-monitoring, as reflected by a reduction in amplitude of
      the error-related negativity (ERN) in comparison to those with longer sleep
      duration. These findings suggest that natural variations in sleep quantity are
      associated with atypical error detection.

PMID- 30290199
TI  - Effects of exposure to extremely low-frequency electromagnetic fields on spatial
      and passive avoidance learning and memory, anxiety-like behavior and oxidative
      stress in male rats.
AB  - There are many controversies about the safety of extremely low-frequency
      electromagnetic field (ELF-EMF) on body health and cognitive performance. In the
      present study, we explored the effects of ELF-EMF on oxidative stress and
      behaviors of rats. Seventy-two adult male Wistar rats were randomly divided into
      following groups, control, sham exposure group and the ELF-EMF exposure groups (1
      MUT, 100 MUT, 500 MUT, and 2000 MUT). After 60 days exposure (2 h/day), elevated
      plus maze (EPM), Morris water maze (MWM) and Passive avoidance learning (PAL)
      tasks were used to evaluate the anxiety-like behavior, spatial and passive
      learning and memory, respectively. Some days after behavioral examination,
      oxidative stress markers were measured. During spatial reference memory test,
      animals in ELF-EMF exposure groups (100, and 2000 MUT) spent more time in target
      zone (F (4, 55) = 5.699, P = 0.0007, One-way ANOVA). In PAL retention, the step
      through latency in the retention test (STLr) in ELF-EMF exposure groups (100,500,
      and 2000 MUT) was significantly greater than control group (F (4, 55) = 29.13, P
      < 0.0001, One-way ANOVA). In EPM test, ELF-EMF exposure (500 and 2000 MUT)
      decreased the percentage of the entries into the open arms (F (4, 55) = 26.31, P
      < 0.0001, one-way ANOVA). ELF-EMF exposure (100, and 500 MUT) increased
      Malondialdehyde (MDA) concentration (F (4, 25) = 79.83, P < 0.0001, One-way
      ANOVA). Our results may allow the conclusion that exposure to ELF-EMFs can
      improve memory retention (but not acquisition) in the adult male rats. Although
      exposure to ELF-EMFs could be a factor in the development of anxious state or
      oxidative stress.

PMID- 30290200
TI  - Endocannabinoids, exercise, pain, and a path to health with aging.
AB  - Physical activity is an important lifestyle factor for growth, development, and
      sustained health throughout life. In recent years, the benefits of physical
      activity have drawn more attention to its physiological effects on the body,
      including well-being. The endocannabinoid system (ECS) has emerged as a focal
      point to ascertain the mechanisms for how exercise benefits the body and how it
      reduces or controls pain. The ECS, its ligands [the endocannabinoids (eCB)],
      receptors (CB1 and CB2), enzymes for the synthesis and degradation of eCB, and
      the polyunsaturated fatty acids (PUFA) that serve as substrates, comprise a
      powerful biological organization of multiple controls that affects mood,
      inflammation, pain, and other neurological aspects of the central nervous system
      and peripheral nervous system. Recently, investigators have reported increases in
      circulating levels of eCB after exercise, with some eCB exerting analgesic
      effects from exercise. The focus of this review is to discuss evidence for the
      role of eCB and the complexities of the ECS in exercise and pain. Some aspects
      presented herein are production of eCB and activation of the cannabinoid
      receptors in the brain following exercise; eCB, pain, and physical activity;
      oxylipins; and joint pain. Future research on the ECS must include mechanistic
      approaches to endocannabinoid signaling and explain the role of dietary PUFA in
      altering signaling of the receptors that affects pain. Additionally, how other
      types of exercise, such as Tai Chi, which is reported to improve well-being,
      should be investigated to ascertain if changes in eCB mediate the mind and body
      benefits of Tai Chi. As we age, exercise in the form of play has evolved with the
      exploration of our body from walking to running, recreational, and competitive
      sports, to midlife physical activity focusing on maintaining fitness and a
      healthy body weight. Furthermore, exercise has been a target of investigation to
      explore various hypotheses to explain the mechanisms for cognitive benefits in
      the young and in older adults. The science of exercise has matured to a level of
      importance in the life cycle to reduce pain with aging and include new
      investigations on the ECS to explain its role in well-being and improved quality
      of life in later years.

PMID- 30290201
TI  - Interactions of the tricyclic antidepressant drug amitriptyline with L-DOPA in
      the striatum and substantia nigra of unilaterally 6-OHDA-lesioned rats. Relevance
      to motor dysfunction in Parkinson's disease.
AB  - Antidepressant drugs are recommended for the treatment of Parkinson's disease
      (PD)-associated depression but their role in the modulation of L-DOPA-induced
      behavioral and neurochemical markers is poorly explored. The aim of the present
      study was to examine the impact of the tricyclic antidepressant amitriptyline and
      L-DOPA, administered chronically alone or in combination, on rotational behavior,
      monoamine levels and binding of radioligands to their transporters in the
      dopaminergic brain structures of unilaterally 6-OHDA-lesioned rats. Binding of
      [3H]nisoxetine to noradrenaline transporter (NET), [3H]GBR 12,935 to dopamine
      transporter (DAT) and [3H]citalopram to serotonin transporter (SERT) were
      analyzed by autoradiography. Amitriptyline administered alone did not induce
      rotational behavior but in combination with L-DOPA increased the number of
      contralateral rotations much more strongly than L-DOPA alone. The combined
      treatment also significantly increased the tissue dopamine (DA) content in the
      ipsilateral striatum and substantia nigra (SN) vs. L-DOPA alone. 6-OHDA-mediated
      lesion of nigrostriatal DA neurons drastically reduced DAT and NET bindings in
      the ipsilateral striatum. In the ipsilateral SN, DAT binding decreased while NET
      binding rose. SERT binding increased significantly mainly in the SN.
      Amitriptyline administered alone or jointly with L-DOPA had no effect on DAT
      binding on the lesioned side, significantly decreased SERT binding in the
      striatum and SN while NET binding only in the SN. Since in the DA-denervated
      striatum, SERT is mainly responsible for reuptake of L-DOPA-derived DA while in
      the SN, SERT and NET are involved, the inhibition of these transporters by
      antidepressant drugs may improve dopaminergic transmission and consequently motor
      behavior.

PMID- 30290202
TI  - Insert sequences of CRISPR/Cas system regulate horizontal antibiotic gene
      transfer in Shigella.
AB  - Multidrug resistances Shigella is an enormous threat of public health. The
      resistance genes always located in plasmids, phages and integrons, which get into
      bacteria cells by horizontal gene transfer (HGT). CRISPR-Cas systems are adaptive
      immune systems in bacteria that are beneficial to resist phage infection and
      other mobile genetic elements. But this can come at a cost of inhibiting the
      acquisition of other beneficial genes through HGT. Here, we investigate how
      Shigella regulate the activity of the CRISPR/Cas system spontaneously, when it
      wants acquire exogenous gene that is necessary for its survival. We found that IS
      elements were identified in cas genes, such as IS600 in cse2, ISSfl2 in cas6e,
      IS629 in cse1- cas3. The number of spacers in CRISPR/Cas which strain containing
      IS was fewer compare with none IS. Interestingly, fewer spacers were also found
      in multi-drug resistance Shigella strains. Furthermore, we have constructed the
      genetic transferred antibiotic resistant strain by resistance plasmid transfer,
      to detect the CRISPR/Cas system changes in this two group strains. We found that
      cse2 gene had a new IS elements (IS600) in the antibiotic-resistant strain. The
      bioinformatics analyses showed that the IS600 insert hotspots in the cse2 gene
      were the TGC-GGC gene motifs and the tertiary structure of the Cse2 protein was
      different with IS600 or not. IS600 could bring a 5-order of magnitude (105)
      decrease in the relative expression of cse2 gene. This study has significant
      implication for further revealing the mechanism underlying the CRISPR/Cas
      mediated antibiotic resistance gene horizontal transfer in Shigella.

PMID- 30290203
TI  - The crux of positive controls - Pro-inflammatory responses in lung cell models.
AB  - Positive controls are an important feature in experimental studies as they show
      the responsiveness of the model under investigation. An often applied reagent for
      a pro-inflammatory stimulus is the endotoxin lipopolysaccharide (LPS), which has
      been shown to induce a cytokine release by various cell cultures. The effect of
      LPS in monocultures of 16HBE14o-, a bronchial cell line, and of A549, an alveolar
      cell line, were compared in submerged and air-liquid interface cultures, as well
      as in co-cultures of the two epithelial cells with monocyte-derived macrophages
      and dendritic cells. The protein and mRNA levels of the two most relevant pro
      inflammatory mediators, Tumor necrosis factor alpha (TNF) and Interleukin 8
      (CXCL8), were measured after 4 h and 24 h exposure. 16HBE14o- cells alone as well
      as in co-cultures are non-responsive to an LPS stimulus, but an already increased
      basal expression of both pro-inflammatory mediators after prolonged time in
      culture was observed. In contrary, A549 in monocultures showed increased CXCL8
      production at the gene and protein level after LPS exposure, while TNF-levels
      were below detection limit. In A549 co-cultured with immune cells both mediators
      were upregulated. This study shows the importance of a careful evaluation of the
      culture system used, including the application of positive controls. In addition,
      the use of co-cultures with immune cells more adequately reflects the
      inflammatory response upon exposure to toxicants.

PMID- 30290204
TI  - Short term exposure to oxycodone alters the survival, proliferation and
      differentiation of rat embryonic neural stem cell in vitro.
AB  - As one of several opioids, oxycodone has been widely used, particularly in
      postoperative analgesia in children and cesarean section. However, the effect of
      oxycodone on developing brain still remains to be seen. Since there is a link
      between anesthetics exposure and long-term behavioral or cognitive dysfunction in
      young children, in the current study, the direct effect of oxycodone on neural
      stem cells (NSCs) biological behaviors was investigated. After exposed to a high
      dose of oxycodone (10 MUg/mL) for 48 h, NSCs survival and proliferation were
      significantly reduced, while NSCs apoptosis and differentiation were enhanced.
      These effects were significantly weaker than that when exposed to same dose of
      morphine. No significant difference was observed regarding to above biological
      behaviors when exposed to lower doses (0.1 MUg/mL and 1.0 MUg/mL) of oxycodone.
      The antagonist of opioid receptor, nalmefene, successfully reversed the influence
      of oxycodone. Taken together, our results indicated that short term exposure to
      oxycodone in low dose might be allowed for developing brain.

PMID- 30290205
TI  - The effects of repeated exposure and variety on vegetable intake in pre-school
      children.
AB  - Children's vegetable consumption in the UK remains lower than national
      recommendations, presenting potential long-term health risks. It is known that
      repeated exposure promotes intake of novel vegetables and that offering children
      variety and choice can also encourage intake. The current study aimed to compare
      the impact of offering variety over simple repeated exposure as a strategy for
      increasing pre-school children's vegetable consumption. Children (N = 95) aged 24
      55 months were recruited through participating nurseries and assigned to receive
      repeated exposure (RE) to a single vegetable snack or a mixed snack consisting of
      five different vegetables (variety: V). A minimum of 5 (maximum 6) exposures were
      given for both RE and V conditions. Pre and post-intervention intake measures of
      both the RE and V snacks were taken for each child. Follow up measures took place
      1 month post-intervention (n = 40). Vegetable intake increased significantly from
      pre to post intervention for snacks congruent to the condition to which children
      were assigned. Magnitude of change was smaller for the variety condition. Follow
      up data revealed that snack intake remained significantly higher than baseline 1
      month post-intervention (p < 0.001). In agreement with previous work this study
      confirmed that repeated exposure was effective in promoting children's vegetable
      intake but there was no additional benefit of variety in this context. It may be
      that for moderately familiar vegetables, serving them alone encourages intake and
      for this age group, avoids contamination fears or effects of neophobia.

PMID- 30290207
TI  - Clinical considerations for the inclusion of individuals with autism spectrum
      disorder in clinical trials.
AB  - Diagnoses of autism spectrum disorder (ASD) have increased considerably over the
      past 20 years. Because of this rise and the inherent complexity of ASD, there is
      a need for an increased number of scientifically valid basic and clinical
      research studies addressing this disorder. This manuscript serves as an
      introduction to the clinical presentation of ASD as well as the unique challenges
      and modifications required to conduct clinical research with this population.
      This includes detailing the current diagnostic criteria, process of receiving an
      ASD diagnosis, information on assessment measures, and special considerations
      when developing research. It is the hope that this information will provide
      researchers interested in conducting clinical trials with those with ASD with
      baseline information and considerations when developing their research topics and
      methodology.

PMID- 30290206
TI  - Repeat ablation for paroxysmal atrial fibrillation - Does adenosine play a role
      in predicting pulmonary vein reconnection patterns?
AB  - BACKGROUND: Pulmonary vein (PV) reconduction after PV isolation (PVI) unmasked by
      adenosine is associated with a higher risk for paroxysmal atrial fibrillation
      (PAF) recurrence. It is unknown if the reconnected PVs after adenosine testing
      and immediate re-ablation can predict reconnection and reconnection patterns of
      PVs at repeat procedures. We assessed reconnection of PVs with and without
      dormant-conduction (DC) during the first and the repeat procedure. METHODS: We
      included 67 patients undergoing PVI for PAF and a second procedure for PAF
      recurrence. DC during adenosine administration at first procedure was seen in 31
      patients (46%). 264 PVs were tested with adenosine; DC was found in 48 PVs (18%)
      and re-ablated during first procedure. During the second procedure, all PVs where
      checked for reconnection. RESULTS: Fifty-eight patients (87%) showed PV
      reconnection during the second procedure. Reconnection was found in 152/264 PVs
      (58%). Of 216 PVs without reconnection during adenosine testing at the first
      ablation, 116 PVs (53.7%) showed reconnection at the repeat procedure. Overall,
      14.9% of patients showed the same PV reconnection pattern in the first and second
      procedure, expected statistical probability of encountering the same reconnection
      pattern was only 6.6%(p = 0.012). CONCLUSIONS: In repeat procedures PVs showed
      significantly more often the same reconnection pattern as during first procedure
      than statistically expected. More than 50% of initial isolated PVs without
      reconnection during adenosine testing showed a reconnection during repeat
      ablation. Techniques to detect susceptibility for PV re-connection like prolonged
      waiting-period should be applied. Elimination of DC should be expanded from
      segmental to circumferential re-isolation or vaster RF application.

PMID- 30290208
TI  - Translational machine learning for psychiatric neuroimaging.
AB  - Despite its initial promise, neuroimaging has not been widely translated into
      clinical psychiatry to assist in the prediction of diagnoses, prognoses, and
      optimal therapeutic strategies. Machine learning approaches may enhance the
      translational potential of neuroimaging because they specifically focus on
      overcoming biases by optimizing the generalizability of pipelines that measure
      complex brain patterns to predict targets at a single-subject level. This article
      introduces some fundamentals of a translational machine learning approach before
      selectively reviewing literature to-date. Promising initial results are then
      balanced by the description of limitations that should be considered in order to
      interpret existing research and maximize the possibility of future translation.
      Future directions are then presented in order to inspire further research and
      progress the field towards clinical translation.

PMID- 30290209
TI  - Metastasis and chemoresistance in CD133 expressing pancreatic cancer cells are
      dependent on their lipid raft integrity.
AB  - Metabolic rewiring is an integral part of tumor growth. Among metabolic pathways,
      the Mevalonic-Acid-Pathway (MVAP) plays a key role in maintaining membrane
      architecture through cholesterol synthesis, thereby affecting invasiveness. In
      the current study, we show for the first time that CD133Hi pancreatic tumor
      initiating cells (TIC) have increased expression of MVAP enzymes, cholesterol
      content and Caveolin expression. Further, we show that CD133 in these cells is
      localized in the lipid-rafts (characterized by Cav-1-cholesterol association).
      Disruption of lipid-rafts by either depleting Cav-1 or by inhibiting MVAP by
      lovastatin decreased metastatic-potential and chemoresistance in CD133Hi cells
      while not affecting the CD133lo cells. Additionally, disruption of lipid-raft
      results in deregulation of FAK-signaling, decreasing invasiveness in pancreatic
      TICs. Furthermore, this also inhibits ABC-transporter activity resulting in
      sensitizing TICs to standard chemotherapeutic agents. Repurposing existing drugs
      for new clinical applications is one of the safest and least resource intensive
      approaches to improve therapeutic options. In this context, our study is
      extremely timely as it shows that targeting lipid-rafts with statins can
      sensitize the normally resistant pancreatic TICHi-cells to standard chemotherapy
      and decrease metastasis, thereby defining a novel strategy for targeting the
      TICHi-PDAC.

PMID- 30290210
TI  - S1PR2 antagonist alleviates oxidative stress-enhanced brain endothelial
      permeability by attenuating p38 and Erk1/2-dependent cPLA2 phosphorylation.
AB  - Both sphingosine-1-phosphate receptor-2 (S1PR2) and cytosolic phospholipase A2
      (cPLA2) are implicated in the disruption of cerebrovascular integrity in
      experimental stroke. However, the role of S1PR2 in induction of cPLA2
      phosphorylation during cerebral ischemia-induced endothelial dysfunction remains
      unknown. This study investigated the effect of S1PR2 blockade on oxidative stress
      induced cerebrovascular endothelial barrier impairment and explored the possible
      mechanisms. In bEnd3 cells, cPLA2 inhibitor CAY10502 as well as S1PR2 antagonist
      JTE013 profoundly suppressed hydrogen peroxide (H2O2)-induced changes of
      paracellular permeability and ZO-1 localization. Besides p38, extracellular
      signal-regulated kinase (Erk) 1/2 is required for H2O2-increased cPLA2
      phosphorylation and endothelial permeability. Pharmacological and genetic
      inhibition of S1PR2 significantly suppressed their phosphorylation in response to
      H2O2. Especially lentivirus-mediated knockdown of S1PR2 inhibited H2O2-induced ZO
      1 redistribution and paracellular hyperpermeability. Using the permanent middle
      cerebral artery occlusion (pMCAO) mouse model, we found JTE013 pretreatment
      markedly reduced Evans blue dye (EBD) extravasation and reversed the decrease in
      VE-cadherin, occludin, claudin-5 and CD31 expression in infarcted hemisphere.
      Lentivirus-mediated S1PR2 knockdown also attenuated EBD extravasation.
      Furthermore, JTE013 pretreatment attenuated neurological deficit, brain edema and
      infarction volume. Therefore, our findings suggest the protective effect of
      JTE013 on brain endothelial barrier integrity is likely mediated by suppressing
      p38 and Erk1/2-dependent cPLA2 phosphorylation under oxidative stress.

PMID- 30290211
TI  - Zeasesquiterpene A-E, new sesquiterpenes from the roots of Zea mays.
AB  - Zeasesquiterpene A-E (1-5), five new sesquiterpenes with two cyclohexanes, were
      isolated from the roots of Zea mays. Their structures were elucidated on the
      basis of 1D and 2D NMR spectral data and ECD analysis. A plausible biosynthetic
      pathway for the compounds (1-6) were hypothesized. All isolated compounds were
      screened for cytotoxicities against five human cancer cell lines (A549, MDA-MB
      231, SK-Hep-1, SNU638 and HCT116) in vitro by MTT assay. Compound 4 showed
      potential cytotoxic activities against A549 (14.3 MUMU) and SNU638 (9.7 MUMU). By
      contrast, compound 1 exhibited moderate cytotoxicity to the four human cancer
      cell lines (A549, SK-Hep-1, SUN638 and HCT116), and the IC50 values are from 19.5
      MUMU to 22.5 MUMU.

PMID- 30290212
TI  - The relationship between social anxiety and heartbeat evoked potential amplitude.
AB  - Past research suggests that social anxiety is associated with increased
      processing of cardiac activity. Cognitive theories propose that this is one
      aspect of self-focus, which is driven by concerns that features of the self, such
      as anxiety symptoms, will elicit evaluation from others. We investigated the
      relationship of social anxiety to the cortical processing of heartbeats as
      reflected in the heartbeat evoked potential (HEP) during false feedback of
      accelerated heart rate. Thirty-eight participants with high social anxiety (HSA;
      n = 19) and non-elevated social anxiety (NSA; n = 19) completed a cognitive task
      during which false feedback of accelerated heart rate was randomly provided on
      50% of trials. HEP amplitude was larger in HSAs, but not NSAs, during false
      heartbeat acceleration cues compared to standard cues. HEP amplitude also was
      larger in HSAs compared to NSAs during acceleration cues. HEP amplitude during
      acceleration cues, but not standard cues correlated with social anxiety. Within
      the first second after the R-peak, social anxiety correlated with voltage at Fz
      from 223 to 305 ms. Social concerns about the consequences of anxiety symptoms
      accounted for an indirect relationship between social anxiety and the HEP. These
      data extend prior evidence of increased processing of cardiac activity in
      socially anxious individuals, providing support for cognitive theories.

PMID- 30290213
TI  - The role of the amygdala in enhanced remembrance of negative episodes and
      acquired negativity of related neutral cues.
AB  - Prior research on the interaction between emotion and episodic memory established
      that negatively charged events are better remembered compared to neutral events
      (i.e. enhanced remembrance), as well as that a priori neutral cues that were
      present in the environment during a negative event can attain aversive meaning by
      themselves (i.e. acquired negativity). Improved understanding the neural
      mechanisms that mediate enhanced remembrance of negative episodes and acquired
      negativity of related neutral cues may carry substantial clinical relevance,
      particularly in the context of posttraumatic pathophysiology. In order to address
      this point forty-nine healthy participants completed a novel fMRI task that
      involve the presentation of neutral pictures before and after a series of short
      neutral and aversive video-clips from which the neutral pictures were originally
      extracted, and a subsequent presentation of these pictures as cues for clip
      recall [termed, Picture-Clip-Picture-Recall (PCPR) task]. Behavioral results
      indicate that aversive clips were indeed better remembered compared to neutral
      clips (i.e. enhanced remembrance of negative episode) and that a priori neutral
      pictures that appeared in aversive clips were rated more negatively after
      relative to before the exposure to the aversive clips (i.e. acquired negativity
      of related neutral cues). Whole-brain fMRI analysis revealed that increased
      amygdala activation in response to pictures when presented as cues for clip
      recall predicted successful clip remembrance, particularly remembrance of
      aversive clips. This amygdala activation was also correlated with the magnitude
      of acquired negativity of the cues following their appearance in aversive clips.
      Taken together our findings implicate the PCPR as a novel, naturalistic,
      framework for investigating the neural interface of emotional episodic memory,
      while highlighting the role of the amygdala in enhanced remembrance of negative
      episodes and acquired negativity of related neutral cues. Clinical implications
      are discussed.

PMID- 30290214
TI  - Effects of the pesticide chlorpyrifos on breast cancer disease. Implication of
      epigenetic mechanisms.
AB  - Chlorpyrifos (CPF) is an organophosphorus pesticide used for agricultural pest
      control all over the world. We have previously demonstrated that environmental
      concentrations of this pesticide alter mammary gland histological structure and
      hormonal balance in rats chronically exposed. In this work, we analyzed the
      effects of CPF on mammary tumors development. Our results demonstrated that CPF
      increases tumor incidence and reduces latency of NMU-induced mammary tumors.
      Although no changes were observed in tumor growth rate, we found a reduced
      steroid hormone receptor expression in the tumors of animals exposed to the
      pesticide. Moreover, we analyzed the role of epigenetic mechanisms in CPF
      effects. Our results indicated that CPF alters HDAC1 mRNA expression in mammary
      gland, although no changes were observed in DNA methylation. In summary, we
      demonstrate that the exposure to CPF promotes mammary tumors development with a
      reduced steroid receptors expression. It has also been found that CPF affects
      HDAC1 mRNA levels in mammary tissue pointing that CPF may act as a breast cancer
      risk factor.

PMID- 30290215
TI  - Caspases orchestrate microglia instrumental functions.
AB  - Microglia, the resident immune cells of the brain, can acquire various cell
      phenotypes based on their location and current role. This level of plasticity is
      required to fulfil the vast variety of functions that microglia perform. Adequate
      microglial functions are crucial for a healthy brain. However, microglial
      activation can also contribute to both degenerative/traumatic and proliferative
      diseases. We review current evidence supporting roles for caspases, a family of
      proteases, in the overall control of microglia, from the regulation of their
      activation, their biological functions, to their death. Further, we discuss
      possible roles for these microglial caspase-dependent signaling pathways in brain
      diseases.

PMID- 30290216
TI  - Natural activators of adenosine 5'-monophosphate (AMP)-activated protein kinase
      (AMPK) and their pharmacological activities.
AB  - Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is a
      heterotrimeric enzyme which monitors cellular energy status and regulates
      metabolism with energy balance. AMPK activation, as a master regulator of
      metabolism, plays role in key tissues like liver, skeletal muscles, and heart as
      well as central nervous system (CNS). Activation of the enzyme by indirect
      activators attracts scientific attentions to treat diabetes, obesity, cancer, and
      other related metabolic disorders like physiological and pathophysiological
      states in CNS. A number of hormones and pharmacological agents have been reported
      to activate AMPK including paroxetine, metformin, thiazolidinediones,
      adiponectin, leptin, interleukin-6, and etc. AMPK activity is prominent in
      regulation of glucose, lipid, and proteins metabolism as well as mitochondrial
      biogenesis and autophagy. Activation of AMPK in the liver decrease blood glucose
      and in skeletal muscles stimulates glucose uptake independently of insulin
      through modulation of activity of several downstream substrates. Activation of
      AMPK inhibits synthesis and induces oxidation of fatty acids, which may reduce
      ectopic lipid accumulation and improve insulin action. The enzyme activation
      promotes cardiovascular homeostasis by ensuring optimum redox balance of heart
      and vascular tissue. In addition, AMPK signaling may link to cancer development
      via regulation of checkpoints of cell cycle. Numerous of conventional drugs have
      been derived from natural resources, while the application of this fruitful
      source of chemical structures have not been explored in depth. A number of these
      compounds are discussed in this review that exhibit beneficial effects in
      metabolic disorders through AMPK activation.

PMID- 30290217
TI  - Novel ABCA1 peptide agonists with antidiabetic action.
AB  - Previously, apoE-derived ABCA1 agonist peptides have been shown to possess anti
      atherosclerotic and possibly antidiabetic properties. Here we assessed the in
      vitro and in vivo actions of a second generation of ABCA1 peptide agonists,
      CS6253 and T6991-2, on glucose homeostasis. The results show that these two
      peptides improve glucose tolerance in a prediabetic diet-induced obesity mouse
      model by enhancing insulin secretion. It was further demonstrated that T6991-2
      also improved glucose tolerance in leptin-deficient (ob/ob) mice. CS6253
      increased insulin secretion both under basal conditions and in response to high
      glucose stimulation in pancreatic INS-1 beta-cells rendered leptin receptor
      deficient with specific siRNA. Additional in vitro cell studies suggest that the
      CS6253 agonist attenuates hepatic gluconeogenesis and glucose transport. It also
      potentiates insulin-stimulated glucose uptake and utilization. These observed
      anti-diabetic actions suggest additional benefits of the CS6253 and T6991-2 ABCA1
      peptide agonists for cardiovascular disease beyond their direct anti
      atherosclerosis properties previously described.

PMID- 30290218
TI  - Targeting glutathione S-transferase P and its interactome with selenium compounds
      in cancer therapy.
AB  - The glutathione (GSH) S-transferase family of detoxification and signalling
      proteins represents a major hub for the metabolism of Selenium-derived compounds.
      At the same time, these compounds can be used to modulate the expression and
      multiple activities of GSTs and other glutathione-dependent genes, that are
      important aspects in both the chemoprevention and therapy of drug-resistant
      cancers. In this context, the isoform GSTP-1 (GSTP) appears to play a fundamental
      role. Besides promoting GSH-dependent detoxification of cellular electrophiles,
      GSTP physically interacts with a number of small molecules and cellular proteins
      producing regulatory effects across the main signal transduction and
      transcription pathways (identified as the "regulatory interactome of GSTP"). An
      emerging molecular mechanism behind such regulatory function is the activity of
      GSTP as a redox chaperonine responsible for the selective glutathionylation of
      protein Cys residues in the different subcellular compartments. The redox
      sensitive transcription factor Nrf2 was recently identified as one of the
      regulatory nodes of this interactome at the interface between inflammation,
      adaptive stress response, and cell death pathways. The influence of Nrf2 in the
      stress response to cellular electrophiles and its regulatory interaction with
      GSTP are discussed in this review suggesting the hypothesis that this interaction
      may represent the actual pharmacological target of Se compounds with thiol
      peroxidase activity. These points are critically evaluated with a view to further
      development of these compounds in cancer prevention and the chemotherapy of drug
      resistant tumours.

PMID- 30290219
TI  - An improved water-soluble prodrug of propofol with high molecular utilization and
      rapid onset of action.
AB  - Water-soluble prodrugs of propofol often carry an excess of propofol at the
      effective dose and have a slower onset of action. Sustained release of the
      original drug can result in propofol accumulation in the body after
      administration, causing delays in wakefulness. This situation causes the prodrug
      to lose the benefits of rapid onset and recovery from the effects of propofol. In
      the present study, HX0921 (sodium 2-(2-(2,6-diisopropylphenoxy)-2
      oxoethoxy)acetate), an improved prodrug of propofol with high utilization of
      propofol and fast onset of action, was studied. The rate of propofol release from
      HX0921 was much faster than that from fospropofol (a marketed propofol prodrug)
      in rat plasma. The 50% effective dose (ED50) of propofol, HX0921 and fospropofol
      to induce anesthesia in rats was 5.78, 22.19 and 42.44 mg/kg, respectively. After
      administration at 2 * ED50, the onset time of anesthesia in the HX0921 group was
      significantly shorter than that in the fospropofol group (0.26 +/- 0.15 min vs.
      2.24 +/- 0.35 min, P < 0.01) and the duration of anesthesia in the HX0921 group
      was also significantly shorter than that in the fospropofol group (22.35 +/- 4.05
      min vs. 29.15 +/- 5.25 min, P < 0.01). These results suggest that the rapid onset
      and short action time of HX0921 was due to the rapid release and high molecular
      utilization of propofol carried by HX0921.

PMID- 30290220
TI  - Production of Phosphorylated Ric-8A proteins using protein kinase CK2.
AB  - Resistance to Inhibitors of Cholinesterase-8 (Ric-8) proteins are molecular
      chaperones that fold heterotrimeric G protein alpha subunits shortly after
      biosynthesis. Ric-8 proteins also act as test tube guanine nucleotide exchange
      factors (GEF) that promote Galpha subunit GDP for GTP exchange. The GEF and
      chaperoning activities of Ric-8A are regulated by phosphorylation of five serine
      and threonine residues within protein kinase CK2 consensus sites. The traditional
      way that Ric-8A proteins have been purified is from Spodoptera frugiperda (Sf9)
      or Trichoplusia ni (Tni) insect cells. Endogenous insect cell kinases do
      phosphorylate the critical regulatory sites of recombinant Ric-8A reasonably
      well, but there is batch-to-batch variability among recombinant Ric-8A
      preparations. Additionally, insect cell-production of some Ric-8 proteins with
      phosphosite alanine substitution mutations is proscribed as there seems to be
      interdependency of multi-site phosphorylation for functional protein production.
      Here, we present a method to produce wild type and phosphosite mutant Ric-8A
      proteins that are fully occupied with bound phosphate at each of the regulatory
      positions. Ric-8A proteins were expressed and purified from E. coli. Purified Ric
      8A was phosphorylated in vitro with protein kinase CK2 and then re-isolated to
      remove kinase. The phosphorylated Ric-8A proteins were ~99% pure and the
      completeness of phosphorylation was verified by chromatography, phos-tag SDS-PAGE
      mobility shifts, immunoblotting using phospho-site specific antibodies, and mass
      spectrometry analysis. E. coli-produced Ric-8A that was phosphorylated using this
      method promoted a faster rate of Galpha subunit guanine nucleotide exchange than
      Ric-8A that was variably phosphorylated during production in insect cells.

PMID- 30290221
TI  - A complete enzymatic capacity for long-chain polyunsaturated fatty acid
      biosynthesis is present in the Amazonian teleost tambaqui, Colossoma macropomum.
AB  - In vertebrates, the essential fatty acids (FA) that satisfy the dietary
      requirements for a given species depend upon its desaturation and elongation
      capabilities to convert the C18 polyunsaturated fatty acids (PUFA), namely
      linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3), into the
      biologically active long-chain (C20-24) polyunsaturated fatty acids (LC-PUFA),
      including arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3)
      and docosahexaenoic acid (DHA, 22:6n-3). Recent studies have established that
      tambaqui (Colossoma macropomum), an important aquaculture-produced species in
      Brazil, is a herbivorous fish that can fulfil its essential FA requirements with
      dietary provision C18 PUFA LA and ALA, although the molecular mechanisms
      underpinning such ability remained unclear. The present study aimed at cloning
      and functionally characterizing genes encoding key desaturase and elongase
      enzymes, namely fads2, elovl5 and elovl2, involved in the LC-PUFA biosynthetic
      pathways in tambaqui. First, a fads2-like desaturase was isolated from tambaqui.
      When expressed in yeast, the tambaqui Fads2 showed Delta6, Delta5 and Delta8
      desaturase capacities within the same enzyme, enabling all desaturation reactions
      required for ARA, EPA and DHA biosynthesis. Moreover, tambaqui possesses two
      elongases that are bona fide orthologs of elovl5 and elovl2. Their functional
      characterization confirmed that they can operate towards a variety of PUFA
      substrates with chain lengths ranging from 18 to 22 carbons. Overall our results
      provide compelling evidence that demonstrates that all the desaturase and
      elongase activities required to convert LA and ALA into ARA, EPA and DHA are
      present in tambaqui within the three genes studied herein, i.e. fads2, elovl5 and
      elovl2.

PMID- 30290222
TI  - Idebenone is a cytoprotective insulin sensitizer whose mechanism is Shc
      inhibition.
AB  - When insulin binds insulin receptor, IRS1 signaling is stimulated to trigger the
      maximal insulin response. p52Shc protein competes directly with IRS1, thus
      damping and diverting maximal insulin response. Genetic reduction of p52Shc
      minimizes competition with IRS1, and improves insulin signaling and glucose
      control in mice, and improves pathophysiological consequences of hyperglycemia.
      Given the multiple benefits of Shc reduction in vivo, we investigated whether any
      of 1680 drugs used in humans may function as Shc inhibitors, and thus potentially
      serve as novel anti-diabetics. Of the 1680, 30 insulin sensitizers were
      identified by screening in vitro, and of these 30 we demonstrated that 7 bound
      Shc protein. Of the 7 drugs, idebenone dose-dependently bound Shc protein in the
      50-100 nM range, and induced insulin sensitivity and cytoprotection in this same
      100 nM range that clinically dosed idebenone reaches in human plasma. By contrast
      we observe mitochondrial effects of idebenone in the 5,000 nM range that are not
      reached in human dosing. Multiple assays of target engagement demonstrate that
      idebenone physically interacts with Shc protein. Idebenone sensitizes mice to
      insulin in two different mouse models of prediabetes. Genetic depletion of
      idebenone's target eliminates idebenone's ability to insulin-sensitize in vivo.
      Thus, idebenone is the first-in-class member of a novel category of insulin
      sensitizing and cytoprotective agents, the Shc inhibitors. Idebenone is an
      approved drug and could be considered for other indications such as type 2
      diabetes and fatty liver disease, in which insulin resistance occurs.

PMID- 30290223
TI  - The European Society of Cardiology (ESC)/European Society of Hypertension (ESH)
      2018 guidelines for hypertension diagnosis and treatment: New concepts and
      recommendations.

PMID- 30290224
TI  - Plasmodium RON12 localizes to the rhoptry body in sporozoites.
AB  - Invasion of host cells by apicomplexan parasites is mediated by proteins released
      from microneme, rhoptry, and dense granule secretory organelles located at the
      apical end of parasite invasive forms. Microneme secreted proteins establish
      interactions with host cell receptors and induce exocytosis of the rhoptry
      organelle. Rhoptry proteins are involved in target cell invasion as well as the
      formation of the parasitophorous vacuole in which parasites reside during
      development within the host cell. In Plasmodium merozoites, the rhoptry neck
      protein (RON) complex consists of RON2, RON4, and RON5, and interacts with apical
      membrane antigen 1 (AMA1) as a critical structure of the invasion moving
      junction. PfRON12 is known to localize to the rhoptry neck of merozoites, but its
      function remains obscure. The roles of RON proteins are largely unknown in
      sporozoites, the second invasive form of Plasmodium which possesses a conserved
      apical end secretory structure. Here, we confirm that RON12 is expressed in the
      rhoptry neck of merozoites in rodent malaria parasites, whereas in contrast we
      show that RON12 is localized to the rhoptry body in sporozoites. Phenotypic
      analysis of Plasmodium berghei ron12-disrupted mutants revealed that RON12 is
      dispensable for sporogony, invasion of mosquito salivary glands and mouse
      hepatocytes, and development in hepatocytes.

PMID- 30290225
TI  - Flow cytometric assessment of leukocyte kinetics for the monitoring of tissue
      damage.
AB  - Leukocyte populations quickly respond to tissue damage, but most leukocyte
      kinetic studies are not based on multiparameter flow cytometry. We systematically
      investigated several blood leukocyte populations after controlled tissue damage.
      48 patients were assigned to either an anterior or posterolateral total hip
      arthroplasty. Peripheral blood was collected pre-operatively and at 2 h, 24 h, 48
      h, 2 and 6 weeks postoperatively and assessed by flow cytometry for absolute
      counts of multiple leukocyte populations using standardized EuroFlow protocols.
      Absolute counts of leukocyte subsets differed significantly between consecutive
      time points. Neutrophils increased instantly after surgery, while most leukocyte
      subsets initially decreased, followed by increasing cell counts until 48 h. At
      two weeks all leukocyte counts were restored to pre-operative counts. Immune cell
      kinetics upon acute tissue damage exhibit reproducible patterns, which differ
      between the leukocyte subsets and with "opposite kinetics" among monocyte
      subsets. Flow cytometric leukocyte monitoring can be used to minimally invasively
      monitor tissue damage.

PMID- 30290226
TI  - Mesenchymal stem cell-driven activatable photosensitizers for precision
      photodynamic oncotherapy.
AB  - Precise targeting with minimal side effects is of particular interest for
      personalized medicine, although it remains a challenge. Herein, we demonstrate
      precision photodynamic therapy (PDT) utilizing human mesenchymal stem cells
      (MSCs) as cellular vehicles to deliver a new activatable photosensitizer (PcS).
      In vivo real-time optical imaging tests indicated that PcS-loaded MSCs possess
      excellent tumor-homing properties. More importantly, dye transfer assays confirm
      that MSCs precisely transfer PcS into human colon cancer cells (HCT116) via the
      "bystander effect." Upon localized light irradiation, the growth of
      intraperitoneal xenograft tumors was significantly inhibited by the photodynamic
      effect. These findings represent a promising strategy for precise oncotherapy.

PMID- 30290227
TI  - The role of PNPLA1 in omega-O-acylceramide synthesis and skin barrier function.
AB  - The human genome encodes nine enzymes belonging to the patatin-like phospholipase
      domain-containing lipase (PNPLA)/Ca2+-independent phospholipase A2 (iPLA2)
      family. Although most PNPLA/iPLA2 enzymes are widely distributed and act on
      phospholipids or neutral lipids as (phospho)lipases to play homeostatic roles in
      lipid metabolism, the function of PNPLA1 remained a mystery until a few years
      ago. However, the recent finding that mutations in the human PNPLA1 gene are
      linked to autosomal recessive congenital ichthyosis (ARCI), as well as evidence
      obtained from biochemical and gene knockout studies, has shed light on the
      function of this enzyme in skin-specific sphingolipid metabolism rather than
      glycerophospholipid metabolism. PNPLA1 is specifically expressed in
      differentiated keratinocytes and plays a crucial role in the biosynthesis of
      omega-O-acylceramide, a particular class of sphingolipids that is essential for
      skin barrier function. PNPLA1 acts as a unique transacylase that specifically
      transfers linoleic acid from triglyceride to omega-hydroxy fatty acid in
      ceramide, thus giving rise to omega-O-acylceramide. In this review, we overview
      the biosynthetic route and biological role of epidermal omega-O-acylceramide,
      highlight the function of PNPLA1 as a bona fide acylceramide synthase required
      for proper skin barrier function and keratinocyte differentiation, and summarize
      the mutations of PNPLA1 currently identified in ARCI patients. This article is
      part of a Special Issue entitled Novel functions of phospholipase A2 Guest
      Editors: Makoto Murakami and Gerard Lambeau.

PMID- 30290228
TI  - A comparison of growth among growth friendly systems for scoliosis: a systematic
      review.
AB  - BACKGROUND: The optimal method for surgical treatment of early onset scoliosis is
      currently unknown. Although the aim of growth-friendly systems is to reduce the
      curve and maintain growth, there is no consensus on how to measure spinal growth
      during and after the treatment. Different measurements of different segments (T1
      S1, T1-T12, instrumented length) are used for different time points to evaluate
      growth. The aim of this review is to assess what measurements are used and to
      compare the growth-friendly systems based on spinal growth during treatment.
      METHODS: The electronic MEDLINE, EMBASE and Cochrane databases were
      systematically searched for original articles that reported growth for
      traditional growing rods (TGR), VEPTR, Shilla, Magnetically controlled growing
      rods (MCGR) and Luque-trolley systems. All measurements were recorded and
      weighted averages calculated in centimeter per year were compared. RESULTS: We
      included 52 studies (26 TGR, 12 MCGR, 6 VEPTR, 4 Luque-trolley, 1 Shilla and 3
      mixed). Often only one segment was reported (T1-S1 length in 22 studies, T1-T12
      length in 2 studies and instrumented length in 5 studies). The remaining 22
      studies reported T1-S1 length in combination with T1-T12 length (15 studies) or
      instrumented length (8 studies). Spinal growth achieved by initial correction
      only, was a considerable 3.9 cm (based on 34 studies) as well as the spinal
      growth achieved by the final fusion surgery (2.3 cm in 4 studies). To
      specifically assess growth achieved with the system, length gain after initial
      surgery and before final fusion in growth system graduates was considered. Only 4
      TGR studies reported on this "true" spinal growth with 0.6 cm and 0.3 cm per year
      in the T1-S1 and T1-T12 segment respectively. CONCLUSION: Reporting on spinal
      growth is currently inadequate and does not allow a good comparison of different
      techniques. However, all systems often report growth similar to Dimeglio's T1-S1
      spinal growth of 1 cm per year. It should be recognized though that a
      considerable portion of the reported spinal growth is due to the initial and
      final surgical correction and not due to the growth-friendly implant.

PMID- 30290229
TI  - The m6A-methylase complex and mRNA export.
AB  - During synthesis, mRNA undergoes a number of modifications such as capping,
      splicing and polyadenylation. These processes are coupled with the orderly
      deposition of the TREX complex on the mRNA and subsequent recruitment of the NXF1
      P15 heterodimer which stimulates the nuclear export of mature mRNAs. mRNAs also
      undergo a number of internal modifications, the most common of which is the N6
      methyladenosine (m6A) modification. In this review we discuss the recent evidence
      of coupling between the m6A modification, RNA processing and export.

PMID- 30290230
TI  - Dissecting cellulitis of the scalp successfully treated with ALA-PDT: Case
      report.
AB  - A case of recalcitrant dissecting cellulitis of the scalp (DCS) in a 23-year-old
      male patient was treated with 4 times of topical ALA-PDT at intervals of 10-15
      days. The patient responded well without any unbearable adverse effects and
      presented satisfactory effects. Before applying this therapy, the patient and his
      doctors had tried other methods, specifically glucocorticoids, intradermal
      injection, and even surgical treatment, but none of them had presented
      satisfactory effects. This suggests that topical ALA-PDT could be an effective
      and safe alternative for DCS patients who are refractory to other standard
      therapies.

PMID- 30290231
TI  - Skin permeation, biocompatibility and antitumor effect of chloroaluminum
      phthalocyanine associated to oleic acid in lipid nanoparticles.
AB  - The objective of this study was to develop and characterize lipid nanoparticles
      (LNs) containing chloroaluminum phthalocyanine (ClAlPc) to reduce the aggregation
      of the drug and improve its skin penetration and its antitumor effect. LNs were
      prepared and characterized by using stearic acid (SA) as solid lipid and oleic
      acid (OA) as liquid lipid in different proportions. in vitro and in vivo skin
      penetration was evaluated using modified Franz diffusion cells and fluorescence
      microscopy, respectively. in vitro biocompatibility and Photodynamic Therapy
      (PDT) were performed using L929-fibroblasts cell line and A549 cancer cell line
      and melanoma BF16-F10, respectively. OA promoted the increase in the
      encapsulation efficiency and drug loading, reaching values of 95.8% and 4%,
      respectively. The formulation with 40% OA (NLC 40) showed a significantly higher
      (p < 0.01) amount of drug retained in the skin compared to other formulations.
      All formulations developed were considered biocompatible. PDT evidenced the
      antitumor efficacy of NLC 40 with reduced cell viability for approximately 10% of
      cancer cells, demonstrating that the presence of OA in the NLC seems to
      potentialize this antitumor effect. PDT in BF16-F10 melanoma using NLC 40
      resulted in a reduction in mean cell viability of approximately 99%. According to
      the results obtained, the systems developed may be promising for the
      incorporation of ClAlPc in the treatment of skin cancer by photodynamic therapy.

PMID- 30290232
TI  - Microsatellite-based genetic diversity of Dermacentor reticulatus in Europe.
AB  - Dermacentor reticulatus, also known as ornate dog tick, is an important vector of
      the causative agents of various tick-borne diseases in humans, livestock and wild
      animals. The geographical range of D. reticulatus in Europe is fragmented and
      divided into two main zones: The Western European and the Eastern European zone.
      To investigate D. reticulatus population structure through its distribution range
      we used microsatellite markers and compared the genetic diversity of D.
      reticulatus in 26 selected sites in the western and eastern European distribution
      areas. A total of 254 unfed adult D. reticulatus ticks were collected from
      vegetation and genotyped at 5 microsatellite loci, and altogether 26 alleles were
      detected. The overall FST value of pairwise comparisons among 26 sampling sites
      was 0.128 and revealed a moderate genetic differentiation. Bayesian-clustering
      analysis showed that D. reticulatus forms two genetically distinct groups across
      Europe. Division of D. reticulatus distribution range into Eastern European and
      Western European populations with a possible recent overlap in Poland has been
      supported by molecular data obtained in this study.

PMID- 30290233
TI  - Defining the pathogenic threat of envenoming by South African shield-nosed and
      coral snakes (genus Aspidelaps), and revealing the likely efficacy of available
      antivenom.
AB  - While envenoming by the southern African shield-nosed or coral snakes (genus
      Aspidelaps) has caused fatalities, bites are uncommon. Consequently, this venom
      is not used in the mixture of snake venoms used to immunise horses for the
      manufacture of regional SAIMR (South African Institute for Medical Research)
      polyvalent antivenom. Aspidelaps species are even excluded from the
      manufacturer's list of venomous snakes that can be treated by this highly
      effective product. This leaves clinicians, albeit rarely, in a therapeutic vacuum
      when treating envenoming by these snakes. This is a significantly understudied
      small group of nocturnal snakes and little is known about their venom
      compositions and toxicities. Using a murine preclinical model, this study
      determined that the paralysing toxicity of venoms from Aspidelaps scutatus
      intermedius, A. lubricus cowlesi and A. l. lubricus approached that of venoms
      from highly neurotoxic African cobras and mambas. This finding was consistent
      with the cross-genus dominance of venom three-finger toxins, including numerous
      isoforms which showed extensive interspecific variation. Our comprehensive
      analysis of venom proteomes showed that the three Aspidelaps species possess
      highly similar venom proteomic compositions. We also revealed that the SAIMR
      polyvalent antivenom cross-reacted extensively in vitro with venom proteins of
      the three Aspidelaps. Importantly, this cross-genus venom-IgG binding translated
      to preclinical (in a murine model) neutralisation of A. s. intermedius venom
      induced lethality by the SAIMR polyvalent antivenom, at doses comparable with
      those that neutralise venom from the cape cobra (Naja nivea), which the antivenom
      is directed against. Our results suggest a wider than anticipated clinical
      utility of the SAIMR polyvalent antivenom, and here we seek to inform southern
      African clinicians that this readily available antivenom is likely to prove
      effective for victims of Aspidelaps envenoming. BIOLOGICAL SIGNIFICANCE: Coral
      and shield-nosed snakes (genus Aspidelaps) comprise two species and several
      subspecies of potentially medically important venomous snakes distributed in
      Namibia, Botswana, Zimbabwe, Mozambique and South Africa. Documented human
      fatalities, although rare, have occurred from both A. lubricus and A. scutatus.
      However, their venom proteomes and the pathological effects of envenomings by
      this understudied group of nocturnal snakes remain uncharacterised. Furthermore,
      no commercial antivenom is made using venom from species of the genus Aspidelaps.
      To fill this gap, we have conducted a transcriptomics-guided comparative
      proteomics analysis of the venoms of the intermediate shield-nose snake (A. s.
      intermedius), southern coral snake (A. l. lubricus), and Cowle's shield snake (A.
      l. cowlesi); investigated the mechanism of action underpinning lethality by A. s.
      intermedius in the murine model; and assessed the in vitro immunoreactivity of
      the SAIMR polyvalent antivenom towards the venom toxins of A. l. lubricus and A.
      l. cowlesi, and the in vivo capability of this antivenom at neutralising the
      lethal effect of A. s. intermedius venom. Our data revealed a high degree of
      conservation of the global composition of the three Aspidelaps venom proteomes,
      all characterised by the overwhelming predominance of neurotoxic 3FTxs, which
      induced classical signs of systemic neurotoxicity in mice. The SAIMR polyvalent
      antivenom extensively binds to Aspidelaps venom toxins and neutralised, with a
      potency of 0.235 mg venom/mL antivenom, the lethal effect of A. s. intermedius
      venom. Our data suggest that the SAIMR antivenom could be a useful therapeutic
      tool for treating human envenomings by Aspidelaps species.

PMID- 30290234
TI  - Alterations in non-type I collagen biomarkers in osteogenesis imperfecta.
AB  - Osteogenesis imperfecta [1] is a rare disorder of connective tissue caused by
      abnormalities in the synthesis or processing of type I collagen. Type I collagen
      is the most abundant type of collagen and is expressed in almost all connective
      tissues. Given that type I collagen interacts with other collagens based in the
      extracellular matrix (ECM), we hypothesized changes in type I collagen in OI
      would result in perturbations in the homeostasis of other collagen types. We
      measured serum biomarkers of several non-type I collagens in patients with mild
      (type I) and moderate-to-severe (type III/IV) OI. Compared to controls, those
      with moderate-to severe OI had a higher mean level of the synthesis markers of
      collagen III (ProC3) (P = 0.02), and levels of collagen V (ProC5) (P = 0.07) were
      slightly, but not significantly, higher. Degradation markers of collage type IV
      (C4M2) (P = 0.04) and type VI (C6M) (P = 0.003) were also higher. In each case, a
      test for trend suggested levels were higher in moderate-to-severe OI,
      intermediate in mild OI, and lowest in controls (P = 0.06-0.002). These changes
      supports the hypothesis that mutations in type I collagen induce a widespread
      alteration in the ECM, and that the diverse clinical manifestations of OI reflect
      an extensive disruption in ECM biology.

PMID- 30290235
TI  - Sleep and circadian rhythms as possible trait markers of suicide attempt in
      bipolar disorders: An actigraphy study.
AB  - BACKGROUND: The poor prognostic of Bipolar disorders (BD) is closely linked to
      deaths by suicide. Sleep and circadian abnormalities are observed during all
      phases of BD and are also associated with suicide attempt (SA). In this context,
      this study sought to identify specific sleep and circadian rhythms markers
      associated with suicidal attempt in euthymic patients with BD. METHODS: The
      sample (N = 236) comprised 3 groups: 147 patients with BD including 57 with a
      history of SA and 90 without (NoSA), and 89 healthy controls (HC). All
      participants were recorded during 21 days with actigraphy. RESULTS: SA was
      associated with women gender (p = 0.03), familial history of SA (p = 0.03), mixed
      episodes (p = 0.001), and benzodiazepines (p = 0.019). SA, compared to noSA, had
      a morning phase preference (p = 0.04), and were more vigorous on the circadian
      type inventory (p = 0.04), and tended to suffer more from insomnia (45% versus
      25% respectively, p = 0.10). SA was also associated with an earlier onset of
      daily activity assessed with actigraphy (M10 onset: p = 0.01). Backward stepwise
      linear regression indicated that a combination of four variables (Gender, vigour,
      insomnia, M10onset) significantly differentiated patients with SA from NoSA (p =
      0.03). LIMITATIONS: Cross-sectional design, and no examination of suicidal
      behaviors' subgroups such as first attempters or repeaters, or violent suicide
      attempt. CONCLUSIONS: Woman gender, vigorous circadian type, insomnia and an
      earlier daily activity appeared independently associated with SA in BD. If these
      biomarkers are confirmed in prospective studies, they should be screened and used
      to prevent suicide, with the development of personal and targeted
      chronobiological treatments.

PMID- 30290237
TI  - Methionine supplementation stimulates mitochondrial respiration.
AB  - Mitochondria play essential metabolic functions in eukaryotes. Although their
      major role is the generation of energy in the form of ATP, they are also involved
      in maintenance of cellular redox state, conversion and biosynthesis of
      metabolites and signal transduction. Most mitochondrial functions are conserved
      in eukaryotic systems and mitochondrial dysfunctions trigger several human
      diseases. By using multi-omics approach, we investigate the effect of methionine
      supplementation on yeast cellular metabolism, considering its role in the
      regulation of key cellular processes. Methionine supplementation induces an up
      regulation of proteins related to mitochondrial functions such as TCA cycle,
      electron transport chain and respiration, combined with an enhancement of
      mitochondrial pyruvate uptake and TCA cycle activity. This metabolic signature is
      more noticeable in cells lacking Snf1/AMPK, the conserved signalling regulator of
      energy homeostasis. Remarkably, snf1Delta cells strongly depend on mitochondrial
      respiration and suppression of pyruvate transport is detrimental for this mutant
      in methionine condition, indicating that respiration mostly relies on pyruvate
      flux into mitochondrial pathways. These data provide new insights into the
      regulation of mitochondrial metabolism and extends our understanding on the role
      of methionine in regulating energy signalling pathways.

PMID- 30290236
TI  - Rapid and accurate analysis of stem cell-derived extracellular vesicles with
      super resolution microscopy and live imaging.
AB  - Extracellular vesicles (EVs) have prevalent roles in cancer biology and
      regenerative medicine. Conventional techniques for characterising EVs including
      electron microscopy (EM), nanoparticle tracking analysis (NTA) and tuneable
      resistive pulse sensing (TRPS), have been reported to produce high variability in
      particle count (EM) and poor sensitivity in detecting EVs below 50 nm in size
      (NTA and TRPS), making accurate and unbiased EV analysis technically challenging.
      This study introduces direct stochastic optical reconstruction microscopy (d
      STORM) as an efficient and reliable characterisation approach for stem cell
      derived EVs. Using a photo-switchable lipid dye, d-STORM imaging enabled rapid
      detection of EVs down to 20-30 nm in size with higher sensitivity and lower
      variability compared to EM, NTA and TRPS techniques. Imaging of EV uptake by live
      stem cells in culture further confirmed the potential of this approach for
      downstream cell biology applications and for the analysis of vesicle-based cell
      cell communication.

PMID- 30290238
TI  - From APOBEC to ZAP: Diverse mechanisms used by cellular restriction factors to
      inhibit virus infections.
AB  - Antiviral restriction factors are cellular proteins that inhibit the entry,
      replication, or spread of viruses. These proteins are critical components of the
      innate immune system and function to limit the severity and host range of virus
      infections. Here we review the current knowledge on the mechanisms of action of
      several restriction factors that affect multiple viruses at distinct stages of
      their life cycles. For example, APOBEC3G deaminates cytosines to hypermutate
      reverse transcribed viral DNA; IFITM3 alters membranes to inhibit virus membrane
      fusion; MXA/B oligomerize on viral protein complexes to inhibit virus
      replication; SAMHD1 decreases dNTP intracellular concentrations to prevent
      reverse transcription of retrovirus genomes; tetherin prevents release of budding
      virions from cells; Viperin catalyzes formation of a nucleoside analogue that
      inhibits viral RNA polymerases; and ZAP binds virus RNAs to target them for
      degradation. We also discuss countermeasures employed by specific viruses against
      these restriction factors, and mention secondary functions of several of these
      factors in modulating immune responses. These important examples highlight the
      diverse strategies cells have evolved to combat virus infections.

PMID- 30290239
TI  - Induction of early growth response gene 1 (EGR1) by endoplasmic reticulum stress
      is mediated by the extracellular regulated kinase (ERK) arm of the MAPK pathways.
AB  - Endoplasmic reticulum (ER) stress activates three principal signaling pathways,
      collectively known as the unfolded protein response, leading to translational and
      transcriptional control mechanisms that dictate the cell's response as adaptive
      or apoptotic. The present study illustrates that for HepG2 human hepatocellular
      carcinoma cells the signaling pathways triggered by ER stress extend beyond the
      three principal pathways to include mitogen-activated protein kinase (MAPK)
      signaling, leading to activation of transcription from the early growth response
      1 (EGR1) gene. Analysis provided evidence for a SRC-RAS-RAF-MEK-ERK cascade
      mechanism that leads to enhanced phosphorylation of the transcription factor
      ELK1. ELK1 and serum response factor (SRF) are constitutively bound to the EGR1
      promoter and are phosphorylated by nuclear localized ERK. The promoter abundance
      of both phospho-SRF and phopsho-ELK1 was increased by ER stress, but the SRF
      phosphorylation was transient. Knockdown of ELK1 had little effect on the basal
      EGR1 mRNA content, but completely blocked the increase in response to ER stress.
      Conversely, knockdown of SRF suppressed basal EGR1 mRNA content, but had only a
      small effect on the induction by ER stress. This research highlights the
      importance of MAPK signaling in response to ER stress and identifies ELK1 as a
      transcriptional mediator and the EGR1 gene as a target.

PMID- 30290240
TI  - Adducins inhibit lung cancer cell migration through mechanisms involving
      regulation of cell-matrix adhesion and cadherin-11 expression.
AB  - Cell migration is a critical mechanism controlling tissue morphogenesis,
      epithelial wound healing and tumor metastasis. Migrating cells depend on
      orchestrated remodeling of the plasma membrane and the underlying actin
      cytoskeleton, which is regulated by the spectrin-adducin-based membrane skeleton.
      Expression of adducins is altered during tumorigenesis, however, their
      involvement in metastatic dissemination of tumor cells remains poorly
      characterized. This study investigated the roles of alpha-adducin (ADD1) and
      gamma-adducin (ADD3) in regulating migration and invasion of non-small cell lung
      cancer (NSCLC) cells. ADD1 was mislocalized, whereas ADD3 was markedly
      downregulated in NSCLC cells with the invasive mesenchymal phenotype. CRISPR/Cas9
      mediated knockout of ADD1 and ADD3 in epithelial-type NSCLC and normal bronchial
      epithelial cells promoted their Boyden chamber migration and Matrigel invasion.
      Furthermore, overexpression of ADD1, but not ADD3, in mesenchymal-type NSCLC
      cells decreased cell migration and invasion. ADD1-overexpressing NSCLC cells
      demonstrated increased adhesion to the extracellular matrix (ECM), accompanied by
      enhanced assembly of focal adhesions and hyperphosphorylation of Src and
      paxillin. The increased adhesiveness and decreased motility of ADD1
      overexpressing cells were reversed by siRNA-mediated knockdown of Src. By
      contrast, the accelerated migration of ADD1 and ADD3-depleted NSCLC cells was ECM
      adhesion-independent and was driven by the upregulated expression of pro-motile
      cadherin-11. Overall, our findings reveal a novel function of adducins as
      negative regulators of NSCLC cell migration and invasion, which could be
      essential for limiting lung cancer progression and metastasis.

PMID- 30290242
TI  - Tub and beta-catenin play a key role in insulin and leptin resistance-induced
      pancreatic beta-cell differentiation.
AB  - The aim of this study was to investigate the molecular mechanism of pancreatic
      islet-derived mesenchymal stem cell (PID-MSC) differentiation into beta-cells in
      the presence of insulin and leptin resistance stimulators. We determined that
      beta-cell differentiation was stimulated by glucose, insulin, and leptin. Co
      administration of insulin and leptin resulted in greater, at a further stage of
      differentiation but non-functional beta-cell formation. The levels of p
      AKT(Ser473) did not change; SOCS3, PTP1B, p-IRS1(Ser307), PTEN levels increased
      and p-IRS1(Try) levels decreased due to insulin and leptin co-administration.
      These findings suggest that co-administration of insulin and leptin to PID-MSCs
      results in the development of both insulin and leptin resistance together. We
      showed that this differentiation signaling is mainly mediated by AKT/GSK
      3beta/beta-catenin and Tub. Moreover, beta-catenin and Tub were linked to each
      other in the nucleus under this condition. Furthermore, we found that Tub and
      beta-catenin contributes to insulin production by increasing the expression of
      transcription factors by binding to the promoter regions of ins1, ins2, and pdx1
      genes. In addition, Tub is also bound to the promoter region of the MafA gene.
      These findings demonstrate that when insulin and leptin resistance develop
      together in rat PID-MSCs beta-cell differentiation increases markedly via beta
      catenin and Tub. New therapeutic agents that inhibit AKT/GSK-3beta/beta-catenin
      and in particular Tub may help prevent the development or retard the progression
      of type 2 diabetes.

PMID- 30290243
TI  - Peptide-decorated polymeric nanomedicines for precision cancer therapy.
AB  - The advancement of tissue and cell-specific drug delivery systems is a key to
      precision cancer therapy. Peptides, with easy synthesis, low immunogenicity and
      biological functions closely mimicking or surpassing natural proteins, have been
      actively engineered and explored to provide nanomedicines with the ability to
      overcome various extracellular and intracellular delivery barriers ranging from
      phagocytic clearance in the circulation, low tumor penetration, poor cancer cell
      selectivity, inferior cell penetration, to endosomal entrapment as well as poor
      blood brain barrier permeation for brain cancer therapy. Anti-tumor studies with
      peptide-decorated polymeric nanomedicines are currently in the experimental
      stage. Most of the reported peptide-directed polymeric nanomedicines do have a
      rather complex design requiring a multi-step reproducible fabrication process.
      Moreover, many of the proposed peptide-decorated polymeric nanomedicines are
      still not able to effectively overcome the drug delivery cascade barriers.
      Consequently, in order to facilitate clinical translation the complexity of the
      systems has to be reduced, while maintaining the added functions after the
      introduction of the different peptides and further progress has to be made in
      passing the various drug delivery barriers. In this review, we give an overview
      of the rational design, development and preclinical performance of peptide
      decorated polymeric nanomedicines, and further discuss their challenges and
      future perspectives as a next generation cancer treatment modality.

PMID- 30290244
TI  - Potent in vivo lung cancer Wnt signaling inhibition via cyclodextrin-LGK974
      inclusion complexes.
AB  - Activation of the Wnt signaling pathway promotes lung cancer progression and
      contributes to poor patient prognosis. The porcupine inhibitor LGK974, a novel
      orally bioavailable cancer therapeutic in Phase I clinical trials, induces potent
      Wnt signaling inhibition and leads to suppressed growth and progression of
      multiple types of cancers. The clinical use of LGK974, however, is limited in
      part due to its low solubility and high toxicity in tissues that rely on Wnt
      signaling for normal homeostasis. Here, we report the use of host-guest chemistry
      to enhance the solubility and bioavailability of LGK974 in mice through
      complexation with cyclodextrins (CD). We assessed the effects of these complexes
      to inhibit Wnt signaling in lung adenocarcinomas that are typically driven by
      overactive Wnt signaling. 2D 1H NMR confirmed host-guest complexation of CDs with
      LGK974. CD:LGK974 complexes significantly decreased the expression of Wnt target
      genes in lung cancer organoids and in lung cancer allografts in mice. Further,
      CD:LGK974 complexes increased the bioavailability upon oral administration in
      mice compared to free LGK974. In a mouse lung cancer allograft model, CD:LGK974
      complexes induced potent Wnt signaling inhibition with reduced intestinal
      toxicity compared to treatment with free drug. Collectively, the development of
      these complexes enables safer and repeated oral or parenteral administration of
      Wnt signaling inhibitors, which hold promise for the treatment of multiple types
      of malignancies.

PMID- 30290241
TI  - Who guards the guardian? Mechanisms that restrain APC/C during the cell cycle.
AB  - The cell cycle is principally controlled by Cyclin Dependent Kinases (CDKs),
      whose oscillating activities are determined by binding to Cyclin coactivators.
      Cyclins exhibit dynamic changes in abundance as cells pass through the cell
      cycle. The sequential, timed accumulation and degradation of Cyclins, as well as
      many other proteins, imposes order on the cell cycle and contributes to genome
      maintenance. The destruction of many cell cycle regulated proteins, including
      Cyclins A and B, is controlled by a large, multi-subunit E3 ubiquitin ligase
      termed the Anaphase Promoting Complex/Cyclosome (APC/C). APC/C activity is
      tightly regulated during the cell cycle. Its activation state increases
      dramatically in mid-mitosis and it remains active until the end of G1 phase.
      Following its mandatory inactivation at the G1/S boundary, APC/C activity remains
      low until the subsequent mitosis. Due to its role in guarding against the
      inappropriate or untimely accumulation of Cyclins, the APC/C is a core component
      of the cell cycle oscillator. In addition to the regulation of Cyclins, APC/C
      controls the degradation of many other substrates. Therefore, it is vital that
      the activity of APC/C itself be tightly guarded. The APC/C is most well studied
      for its role and regulation during mitosis. However, the APC/C also plays a
      similarly important and conserved role in the maintenance of G1 phase. Here we
      review the diverse mechanisms counteracting APC/C activity throughout the cell
      cycle and the importance of their coordinated actions on cell growth,
      proliferation, and disease.

PMID- 30290245
TI  - Exosomes: natural nanoparticles as bio shuttles for RNAi delivery.
AB  - Application of exosomes, natural nanoscale vesicles, as specific delivery
      vehicles has received considerable attention in recent past years. The presence
      of various adhesive proteins on the surface of these lipid bilayers, gives them
      the ability to interact with cellular membranes. Although the function of
      exosomes was not known for some time, further researches have suggested that they
      are effective in multiple cellular pathways, as well as pathogenesis of a broad
      range of diseases including neurodegenerative diseases, cardiovascular diseases,
      and more importantly, multiple human malignancies. As erstwhile research brought
      to light more aspects of exosomes' biogenesis and functions, researchers sought
      to benefit from their effects in therapeutic and diagnostic purposes. Gene
      therapy is one of these fields that has seen many endeavors made. The present
      review article looks at gene therapy and its latest advancements, structure and
      function of exosomes and their role as bio shuttles in various clinical contexts
      relating to gene therapy.

PMID- 30290246
TI  - Prospective evaluation of the adaptive immune response to SlpA in Clostridium
      difficile infection.
AB  - Clostridium difficile is a major cause of healthcare-associated diarrhea. SlpA is
      the precursor of the S-layer of C. difficile. The aim of this work was to
      evaluate the humoral immune response of hospitalized patients to SlpA and its
      potential role on CDI outcome. Sera of 87 included patients were collected the
      day of CDI diagnosis as well as at early and late periods after infection. SlpA
      appeared to be immunogenic with a heterogeneous response between patients after a
      CDI. Patients with a single episode had a significantly higher anti-SlpA IgG
      antibody level than patients with recurrent CDI (p = 0.0197). These preliminary
      results will be useful to understand better the inter-individual variability of
      immune responses to C. difficile as well as for the development of new
      therapeutics.

PMID- 30290247
TI  - Transcranial direct current stimulation modulates the brain's response to foot
      stimuli under dual-task condition: A fMRI study in elderly adults.
AB  - Previous behavioral studies have shown that high-intensity cognitive tasks weaken
      balance control in elder adults. Moreover, age-related loss of plantar sensation
      is considered to be an important contributing factor to the occurrence of falls.
      Recently, we have realized that transcranial direct current stimulation (tDCS)
      can effectively improve the balance of the elderly under the dual-task, but its
      underlying regulatory mechanism is not clear. In this study, task functional
      Magnetic Resonance Imaging (fMRI) was used to study the brain's response to foot
      stimuli under foot stimuli or dual-task (foot stimuli and cognitive task)
      conditions to explain the effect of the addition of cognitive tasks during
      balance in 16 healthy elderly adults. To study whether tDCS would counteract the
      effect of the added cognitive task, we further compared the differences in
      activity of the cerebral cortices of dual-task and tDCS-dual-task conditions. The
      results suggested added cognitive tasks significantly attenuated the response of
      the brain to foot stimuli in elderly adults. Moreover, the cortex excitability
      weakened by cognitive tasks was significantly promoted after 20 min of tDCS. In
      conclusion, a portion of the resources originally used for plantar sensory
      processing may be assigned to the processing of the cognitive task when the
      cognitive tasks are added, which results in insufficient resources for plantar
      sensory processing. tDCS improves the ability of the brain to respond to foot
      stimuli by modulating the excitability of the cognitive cortex and reverses the
      effects of cognitive tasks.

PMID- 30290248
TI  - Zebrafish bio-assay guided isolation of human acetylcholinesterase inhibitory
      trans-tephrostachin from Tephrosia purpurea (L.) Pers.
AB  - An acetylcholinesterase inhibitory compound was isolated from Tephrosia purpurea
      (L.) Pers. by zebrafish brain based bioassay guided isolation and predicted as
      trans-tephrostachin.Enzyme kinetics studies (Line weaver-Burk plots and Michaelis
      Menten equation) favored the reversible / mixed type, with the inhibition
      constant (Ki) of 53.0 +/- 7.4 MUM in zebrafish brain (IC50 value of 39.0 +/- 1.4
      MUM). However, the inhibition constant (Ki) was found to be 36.0 +/- 0.4 MUM with
      IC50 value of 20.0 +/- 1.0 MUM, whereas donepezil showed 3.2 +/- 0.3 MUM with the
      IC50 value of 0.12 +/- 0.04 MUM for human acetylcholinesterase. Further, the
      molecular docking, dynamics and simulation for trans-tephrostachin obtained
      better binding affinity and efficacy than commercial drugs donepezil and
      galanthamine. Hence, the isolated compound trans - tephrostachin from T. purpurea
      shall be further considered for the development of potential drug for the
      counteraction of Alzheimer's disease progression.

PMID- 30290249
TI  - Non-invasive mapping of glutathione levels in mouse brains by in vivo electron
      paramagnetic resonance (EPR) imaging: Applied to a kindling mouse model.
AB  - Glutathione (GSH) is an important antioxidant that can protect cells under
      oxidative stress. Thus, a non-invasive method to measure and map the distribution
      of GSH in live animals is needed. To image the distribution of GSH levels in
      specific brain regions, a new method using electron paramagnetic resonance (EPR)
      imaging with a nitroxide imaging probe was developed. Pixel-based mapping of
      brain GSH levels was successfully obtained by using the linear relationship
      between reduction rates for nitroxides in brains, measured by an in vivo EPR
      imager, and brain GSH levels, measured by an in vitro biochemical assay. The
      newly developed method was applied to a kindling mouse model induced with
      pentylenetetrazole (PTZ) to visualize changes in GSH levels in specific brain
      regions after seizure. The obtained map of brain GSH levels clearly indicated
      decreased GSH levels around the hippocampal region compared to control mice.

PMID- 30290250
TI  - The oxidation of potato starch by Electro-Fenton system in the presence of Fe(II)
      ions.
AB  - An efficient method was developed to prepare oxidized potato starch under the
      pasting point by Electro-Fenton system, in which a complex of sodium citrate and
      Fe2+ (SC-Fe2+) was used as catalyst, and H2O2 was used as oxidant. In the
      preparation process the oxidation degree of starch was controlled by the molar
      ratios of SC-Fe2+ and hydrogen peroxide. The structures and thermal properties of
      the prepared oxidized starch were characterized by FT-IR, XRD, SEM, DSC and DTG.
      The characterization results indicated that the obtained oxidized potato starch
      owned one grainy molecule structure, and displayed a high viscosity (not less
      than 63 Pa.s) by comparing to the raw starch. The carbonyl and carboxyl contents
      of oxidized potato starch achieved 0.81 per 100 AGU and 0.79 per 100 AGU,
      respectively after the raw starch was oxidized. And the oxidized starch showed
      good thermal stability, which can dramatically improve the application
      performance of starch-based biomaterials.

PMID- 30290251
TI  - Isolation and characterization of a galactose-specific lectin (EantH) with
      antimicrobial activity from Euphorbia antiquorum L. latex.
AB  - A homodimeric 75 kDa lectin with hemagglutination activity (HA) was purified from
      the crude latex of Euphorbia antiquorum L. by two types of chromatography, on
      cation exchange (HiTrap SP FF) and hydrophobic HiTrap Phenyl FF (high sub)
      columns. The purified protein was designated EantH, and is classified as a
      galactose-specific thermostable lectin. The HA of EantH was stable at pH values
      of 5-9 and temperature 5-65  degrees C. The lectin had bacteriostatic action on
      the Gram-positive bacteria Staphylococcus aureus and S. epidermidis, with a
      minimum inhibitory concentration (MIC) of 2000 MUg/ml and on a Gram-negative
      bacterium Samonella typhimurium, with a MIC of 1000 MUg/ml. EantH inhibited the
      growth of Propionibacterium acnes and Streptococcus agalactiae with MIC of 125
      MUg/ml and 250 MUg/ml, respectively. EantH killed P. acnes and S. agalactiae with
      a minimum microbicidal concentration (MMC) of 1000 MUg/ml and 2000 MUg/ml,
      respectively. Scanning electron microscopy indicated that binding of EantH to the
      carbohydrates in the cell walls of P. acnes and S. typhimurium drastically
      altered the bacterial cells, and led to inhibition of growth and/or cell death.
      The antimicrobial activity of EantH could be neutralized by d-galactose,
      indicating that its bactericidal action involves binding to galactose in the cell
      wall.

PMID- 30290252
TI  - Fabrication and characterization of composite cryobeads based on chitosan and
      starches-g-PAN as efficient and reusable biosorbents for removal of Cu2+, Ni2+,
      and Co2+ ions.
AB  - Novel composite biosorbents were developed in this work as cryobeads by dual
      cross-linking of a mixture of chitosan (CS) and starch coming from different
      botanical sources, such as potato, wheat, and rice, grafted with
      poly(acrylonitrile) (PAN). Glutaraldehyde and poly(ethylene glycol diglycidyl
      ether) were used as cross-linkers. Composite cryobeads were characterized by
      FTIR, SEM-EDX, and swelling kinetics. Sorption of Cu2+, Ni2+, and Co2+ onto the
      novel biosorbents was investigated as a function of time and the concentration of
      the metal ion, at the optimum pH and sorbent dose. Pseudo-second-order kinetic
      model and Elovich model well fitted the kinetic results, indicating chemisorption
      as the most probable mechanism of sorption, while the Langmuir, and Sips isotherm
      models described the sorption at equilibrium for all metal ions. The values of
      the maximum sorption capacity of Cu2+, Ni2+, and Co2+ onto the composite sorbent
      based on CS and rice starch-g-PAN were as follows: 100.6 mg/g, 83.25 mg/g, and
      74.01 mg/g, respectively. The nitrile groups present in the biocomposites
      CS/starch-g-PAN constitute a source to further increase the sorption capacity by
      their hydrolysis. A remarkable level of reusability was found for the composite
      cryobeads, no decrease of the sorption capacity being observed after five
      consecutive sorption/desorption cycles.

PMID- 30290253
TI  - Influence of photoinitiator concentration and irradiation time on the
      crosslinking performance of visible-light activated pullulan-HEMA hydrogels.
AB  - In-situ forming hydrogels were prepared from pullulan-HEMA copolymer using three
      component visible-light system composed of camphorquinone carboxylic acid-folic
      acid-iodonium salt. The relevance of double bond conversion and crosslinking
      density of hydrogels with the photoinitiator concentration and irradiation time
      were estimated by FT-IR analysis and swelling calculation using Flory-Rehner
      theory, respectively. The results revealed that the crosslinking density and
      degree of conversion of hydrogels were improved by photoinitiator concentration
      increasing until certain extend, then they decreased due to a primary radicals
      termination reaction occurred. The shortest irradiation time of 10 s was
      essential to obtain acceptable hydrogels for further characterizations. For the
      probability use of hydrogels as scaffold was investigated in vitro by measuring
      of the indirect cytotoxicity assay by MTT-assay using human bone Sarcoma cell as
      a reference cell lines. The majority of seeded SW1353 cells maintained a live
      with an accepted viability of ~85-92% over a four days culture period with
      irradiation of hydrogel 10 s, while cell viability has improved to ~95-98% with
      prolonging the irradiation time of hydrogel to 60 s. The current photoinitiating
      system is a proper system for in-situ crosslinking the activated-light
      biomaterials for bone regeneration, dental, or tissue engineering applications.

PMID- 30290254
TI  - Low-resolution envelope, biophysical analysis and biochemical characterization of
      a short-chain specific and halotolerant carboxylesterase from Bacillus
      licheniformis.
AB  - Esterases are widely applied in industrial processes due to their versatility,
      regio- and enantioselectivity, lack of cofactors and stability in organic
      solvents. Bacillus licheniformis, a microorganism frequently used in industrial
      and biotechnological applications such as dairy, baking, beverage, pulp and
      paper, detergent and cosmetics production, organic synthesis and waste
      management, is a promising source of esterases. Here we describe the biochemical
      and biophysical characterization of B. licheniformis carboxylesterase BlEst1 and
      its SAXS-derived molecular envelope. BlEst1 has optimal hydrolytic activity
      against p-nitrophenyl acetate at pH 7.0 and 40  degrees C. Furthermore, BlEst1 is
      stable in different organic solvents such as methanol, isopropanol and butanol.
      The BlEst1 homology model reveals a typical alpha/beta hydrolase core with an
      adjacent auxiliary domain, snuggly fitting the experimental low-resolution SAXS
      molecular envelope. Moreover, BlEst1 maintained considerable part of its activity
      in the presence of up to 5 M NaCl and its thermal stability was significantly
      enhanced by the presence of salt, revealing its halotolerant character. The
      ability to work under harsh conditions makes BlEst1 an interesting candidate for
      industrial applications.

PMID- 30290255
TI  - Comparative analysis of two mitochondrial genomes of flesh flies (Sarcophaga
      antilope and Sarcophaga dux) with phylogeny and evolutionary timescale for
      Sarcophagidae.
AB  - The complete mitochondrial genomes (mitogenomes) of two flesh flies (Sarcophaga
      antilope Bottcher and Sarcophaga dux Thomson) are amplified, sequenced,
      annotated, analyzed, and compared with 13 other species of the family
      Sarcophagidae. The mitogenomes of S. antilope and S. dux are 15,196 bp and 15,731
      bp long, respectively, and each contains the typical set of 37 genes (13 protein
      coding genes (PCGs), 22 transfer RNA (tRNA) genes, and two ribosomal RNA (rRNA)
      genes) and a non-coding control region with identical gene arrangement as typical
      arthropod mitogenome. The phylogenetic trees inferred from Bayesian inference
      (BI) and maximum likelihood (ML) analysis for 15 sarcophagid and five outgroup
      taxa are congruent, both not supporting the monophyly of Sarcophagidae but
      supporting the subfamily Sarcophaginae as a monophyletic group and the tribal
      relationship "Boettcheriini + (Raviniini + (Parasacophagini + Sarcophagini))".
      The molecular dating analyses indicate the Sarcophagidae was first divided within
      the Late Eocene epoch (35.52 million years ago (Mya), 95% high posterior density
      (HPD) interval: 26.70-45.01 Mya), and most Sarcophagini species diverged during
      the Miocene epoch (<17.09 Mya, 95% HPD: 10.76-24.36 Mya).

PMID- 30290256
TI  - Protective roles of Amanita caesarea polysaccharides against Alzheimer's disease
      via Nrf2 pathway.
AB  - This study explores the neuro-protective effects of Amanita caesarea
      polysaccharides (ACPS), obtained by 80% alcohol precipitation of water extract
      and purified using a DEAE-52 cellulose anion exchange column, related to
      antioxidant activity. A 3-h pre-treatment of ACPS prior to l-glutamic acid (l
      Glu) co-exposure reversed the decreased cell viability, inhibited apoptosis,
      suppressed the accumulation of intracellular reactive oxygen species and restored
      mitochondrial membrane potential in HT22 cells. Compared to l-Glu-exposed cells,
      ACPS enhanced the nuclear levels of NF-E2p45-related factor 2 (Nrf2), reduced the
      cytoplasmic levels of Nrf2 and cytochrome C, suppressed the expression of Kelch
      like ECH-associated protein 1, and enhanced the expression of heme oxygenase-1,
      superoxide dismutase 1 and cysteine ligase catalytic subunit. In a d-galactose
      and aluminum trichloride Alzheimer's disease (AD) mouse model, 42-day
      administration of ACPS improved the abnormal behaviors. ACPS suppressed the
      deposition of beta-amyloid peptide in the brain and ameliorated oxidative stress
      via modulating the levels of related enzymes. ACPS improved the functioning of
      the central cholinergic system, as indicated by an increase in acetylcholine and
      choline acetyltransferase concentrations, and reduced acetylcholine esterase
      levels in the serum, hypothalamus and cerebral cortex. Our data suggest that ACPS
      may be a promising candidate for the treatment of AD.

PMID- 30290257
TI  - Evaluation of the production of exopolysaccharide by plant growth promoting yeast
      Rhodotorula sp. strain CAH2 under abiotic stress conditions.
AB  - The capability of plant growth promoting microbes to survive under abiotic
      stresses has important significance for improving plant growth and productivity.
      Among the various plant growth promoting biomolecules produced by microbes,
      exopolysaccharide (EPS) help microbes to survive in inhospitable environments and
      endure environmental stressful conditions. In the present study, a yeast strain
      CAH2 was isolated from Beta vulgaris rhizosphere soil and identified as
      Rhodotorula sp., based on the partial 18S rRNA gene sequence analysis.
      Rhodotorula sp. strain CAH2 was found to tolerate higher concentrations of Al (6
      mM), NaCl (150 mM) and PEG-6000 (15%, w/v). The strain CAH2 was shown to produce
      7.5 g L-1 of EPS in the production medium with sucrose and yeast extract as a
      carbon and nitrogen sources, respectively. The EPS yield was increased constantly
      with increasing concentrations of Al, NaCl and PEG-6000. The structural feature
      of EPS studied through FT-IR and NMR spectral analysis confirmed the presence of
      glucose, mannose and galactose. The yeast strain CAH2 was produced multiple plant
      growth promoting traits in the presence and absence of abiotic stresses. Finally,
      these results indicate that the production of EPS could be safeguard the plant
      growth promoting Rhodotorula sp. strain CAH2 from unfavourable environmental
      conditions.

PMID- 30290258
TI  - Doxorubicin-loaded casein nanoparticles for drug delivery: Preparation,
      characterization and in vitro evaluation.
AB  - Casein, a milk protein that self-assembles to form micelles in aqueous solution,
      can bind to a wide range of drugs (hydrophilic and hydrophobic). Herein, a low
      cost and facile method was reported to prepare casein nanoparticles loaded with
      an anticancer drug, doxorubicin (DOX). The particles were fabricated by adding an
      excess of Ca2+ ions which brings the soluble casein present in the solution into
      the micellar framework to form dense nanoparticles. The binding between the drug
      and the macromolecule was confirmed using fluorescence studies. Circular
      Dichroism (CD) shows that upon addition of excess Ca2+ the protein chains
      rearrange. The nanoparticles were characterized by transmission electron
      microscopy (TEM), field emission scanning electron microscopy (FESEM), and
      dynamic light scattering (DLS). The release at pH 1 was higher than the
      physiological pH making this formulation potent for delivering the drug to the
      stomach via the oral route. The DOX attached with casein showed improved
      efficacy, i.e., better cytotoxicity against human pancreatic carcinoma cell line,
      PANC 1 cells as compared to the free drug of the same concentration, owing to
      higher cell uptake of the macromolecule.

PMID- 30290259
TI  - Influence of the ionic strength on the amyloid fibrillogenesis of hen egg white
      lysozyme.
AB  - The study investigates the role of the electrostatic interactions in the
      fibrillation of the hen egg white lysozyme (HEWL). In order to achieve this aim
      the influence of the cations Na+, Mg2+ and Al3+ on the amyloid fibril formation
      and amorphous aggregation was tested. The amyloids are formed in the solution
      without added salt but the Thioflavin T fluorescence gives the false-negative
      result. In these conditions, the HEWL fibrils are long and curvy. If the ionic
      strength of the solution is sufficiently high, the formed amyloids are shorter
      and fragmented. Our study shows that the addition of the aluminium salt promotes
      protein fibrillation. The amorphous aggregation dominates in the high
      concentration of electrolyte. The in vitro amyloid fibril formation seems to be
      regulated by universal mechanisms. The theories implemented in the polymer
      science or for colloidal solutions give the qualitative description of the
      aggregation phenomena. However, the specific interactions and the additional
      effects (e.g. fibril fragmentation) modulate the amyloidogenesis.

PMID- 30290260
TI  - Overexpression of secreted sucrose isomerase in Yarrowia lipolytica and its
      application in isomaltulose production after immobilization.
AB  - Isomaltulose production by bacterial fermentation was limited, due to generation
      of undesirable products and reduced yields. Isomaltulose production using sucrose
      isomerase (SIase) catalyzed methods was expected to be more applicable, but was
      hampered by low SIase activity and lack of a secreted SIase producer. Here, we
      aimed to obtain high levels of secreted SIase by overexpressing the SIase gene
      from Pantoea dispersa UQ68J in Yarrowia lipolytica, a successful host for
      efficient secretory expression, with a newly characterized strong constitutive
      promoter. After optimization of the culture medium, the engineered strain JD
      secreted SIase with an activity of 49.3 U/mL. The recombinant SIase was
      effectively immobilized onto polyvinyl alcohol-alginate, and the enzymatic
      activity recovery rate was up to 82.4%. The stability of the SIase was
      significantly improved by immobilization. Batch production of isomaltulose
      catalyzed by the immobilized SIase was performed under optimal conditions,
      generating 620.7 g/L isomaltulose with a yield of 0.96 g/g. The conversion rate
      of sucrose after 13 batches remained above 90%. These results demonstrated that
      the proposed SIase expression and immobilization method was promising in the
      industrial production of isomaltulose.

PMID- 30290261
TI  - Influence of spray-drying, freeze-drying and vacuum-drying on physicochemical and
      functional properties of gelatin from Labeo rohita swim bladder.
AB  - Influence of different drying method on yield, physicochemical and functional
      properties of gelatin from rohu (Labeo rohita) swim bladder were investigated.
      Freeze-drying presented the highest gelatin yield (54.51 g/100 g, dry weight
      basis), followed by vacuum-drying (48.95 g/100 g) and spray-drying (41.76 g/100
      g), respectively (P < 0.05). All gelatin samples showed glycine as the major
      amino acid followed by proline, glutamic acid, alanine, arginine and
      hydroxyproline, respectively. Freeze-dried gelatin (FDG) and spray-dried gelatin
      (SDG) showed alpha (alpha1 and alpha2), beta-chains and gamma-chain as the
      predominant components, whereas an absence of beta- and gamma-chains found in
      vacuum-dried gelatin (VDG). FTIR spectra revealed that the loss of the triple
      helix was found in all gelatins which indicated the conversion of collagen to
      soluble gelatin. FDG and SDG had the highest surface hydrophobicity, protein
      solubility, emulsifying, foaming and gelation property than VDG (P < 0.05).
      Moreover, SDG showed slightly higher surface hydrophobicity, protein solubility,
      emulsifying and foaming properties as compared to FDG (P < 0.05). However, no
      significant difference was found in gelation properties of FDG and SDG (P >
      0.05). Therefore, freeze-drying or spray-drying could be an appropriate drying
      method for preparation of gelatin from rohu swim bladder with better
      functionalities.

PMID- 30290262
TI  - A novel milk-clotting cysteine protease from Ficus johannis: Purification and
      characterization.
AB  - Due to the need for calf rennet alternatives, many attempts have been made to
      find new proteases. A novel cysteine protease with milk-clotting activity was
      purified from Ficus johannis by cation exchange chromatography. The protease was
      stable in various pH (3.0-10.5) with the optimum at 6.5 and showed its maximum
      activity at 60  degrees C. The Km and Vmax values of the enzyme were obtained to
      be 0.604 mg/ml and 0.0273 MUmol Tyr/min, respectively. The purified protease
      exhibited considerable activity towards kappa-casein in comparison to alpha
      casein and beta-casein. The enzyme was almost completely active in the presence
      of high salt concentrations. Besides, it had high stability against
      autodigestion. The content of free amino acids was determined by HPLC, where
      leucine, lysine, valine, gamma-aminobutyric acid and tyrosine were the most
      abundant amino acids. The cheese manufactured by using the purified protease
      showed similar textural properties and physico-chemical compositions to cheese
      produced using commercial rennet. Considering the special characteristics,
      including high milk-clotting activity, considerable stability over wide ranges of
      pH and temperature, resistance towards solvents, salts, and surfactants, the new
      protease might be the promising candidate for the dairy industry as well as other
      food and biotechnological industries.

PMID- 30290263
TI  - Up- and downregulation of mature miR-1587 function by modulating its G-quadruplex
      structure and using small molecules.
AB  - Using bioinformatics analysis, we found some mature human miRNAs containing G
      rich sequences with four G-tracts that had a high probability of forming G
      quadruplex structures. Here, we chose G-rich miR-1587 as a model to characterize
      the function and regulation of miRNAs. Using electrospray ionization mass
      spectrometry, magnetic resonance imaging, circular dichroism spectrometry, we had
      confirmed that miR-1587 folded into a stable parallel G-quadruplex structure. By
      microarray, Q-RT-PCR and 3'UTR luciferase assay, TAGLN, an early marker of smooth
      muscle differentiation and tumor suppressor, was identified as a target gene of
      miR-1587, thus providing a direct target to study miR-1587 functions. We
      identified three aspects of miR-1587 regulation: 1) KCl induced miR-1587 G
      quadruplex formation, reducing the interaction between miR-1587 and the target
      gene, and inhibiting miR-1587 function; 2) pseudopalmatine ligand further
      inhibited miR-1587 binding to TAGLN mRNA, which disrupted its function and
      increased the TAGLN expression; 3) the addition of TMPyP4 ligand interfered G
      quadruplex formation, and significantly enhanced miR-1587 regulation of TAGLN
      expression. This study has revealed the possibility of using the G-quadruplex
      structure as a strategy to regulate miR-1587 function, showing potential for the
      development of up- and downregulation of mature G-rich microRNA function by
      modulating its G-quadruplex and using small molecules.

PMID- 30290264
TI  - Structure characterization and anti-leukemia activity of a novel polysaccharide
      from Angelica sinensis (Oliv.) Diels.
AB  - A new water-soluble polysaccharide, APS-1II, with a molecular weight of 42.1 kDa
      was isolated from the roots of Angelica sinensis (Oliv.) Diels. APS-1II consists
      of arabinose (Ara), glucose (Glc) and fucose (Fuc) with a molar ratio of
      2.48:1.05:1.00. The backbone of APS-1II is composed of 1,3-alpha-l-Araf and 1,6
      alpha-d-Glcp with the branches containing 1,5-alpha-l-Araf, 1,4-beta-d-Glcp, T
      beta-d-Glcp, 1,3-alpha-l-Fucp and T-alpha-l-Fucp. APS-1II inhibited the
      proliferation of human leukemia K562 and mouse L1210 cells in vitro and markedly
      prolonged the life span of L1210-bearing mice in vivo. APS-1II also increased the
      numbers of leukocytes and lymphocytes in peripheral blood, and significantly
      decreased plasma tumor necrosis factor, interleukin-2 and interferon-gamma levels
      in L1210-bearing mice. Moreover, APS-1II administration concentration-dependently
      promoted the proliferation of the splenocytes, enhanced phagocytic activity of
      peritoneal macrophages and cytotoxicity of natural killer cells. These results
      suggest that APS-1II could effectively inhibit leukemia and induce a protective
      immune response, and it may be used as a suitable candidate reagent for leukemia
      therapy.

PMID- 30290265
TI  - Role of cell division protein divIVA in Enterococcus faecalis pathogenesis,
      biofilm and drug resistance: A future perspective by in silico approaches.
AB  - Antibiotics resistance is the major problem in clinical settings which leads to
      the emergence of drug resistant bacteria. Biofilm formation is one of the grounds
      for the emergence of antibiotics resistant strains of Enterococcus faecalis. Our
      group previously reported in a comparative proteomic study of biofilm and
      planktonic state of E. faecalis that cell division protein divIVA was two folds
      overexpressed in biofilm state as compared to planktonic one and suggested its
      involvement in biofilm formation and antibiotics resistance. In this in silico
      study molecular docking showed that DNA bind to the conserved amino acid residues
      of divIVA domain and suggested that divIVA possibly secretes DNA into extra
      polymeric substance (EPS) which is the part of biofilm. We also performed the
      STRING analysis of cell division protein divIVA and predicted their interactive
      partners {cell division proteins/divisome complex (ftsZ, ftsA, divIV, ftsL, &
      gpsB), hypothetical proteins (sepF, EF_0261, EF_1000, EF_0998, EF_1006 &
      EF_1040), isoleucyl-tRNA synthetase (ileS), septation ring formation regulator
      (ezrA), S4 domain-containing protein (EF_1001), rod shape-determining protein
      (mreC), UDP-N-acetylmuramoyl-L-alanyl-d-glutamate synthetase (murD), UDP
      diphospho-muramoyl-pentapeptide beta-N- acetylglucosaminyltransferase (murG),
      Lipoprotein signal peptidase (lspA), adenylate kinase (adk) and DNA-binding
      response regulator (vicR)}. We suggest that cumulatively divIVA and its
      interactive partners might be directly or indirectly involved in E. faecalis cell
      division, growth, biofilm formation, virulence and resistance.

PMID- 30290266
TI  - Esculin prevents Lipopolysaccharide/D-Galactosamine-induced acute liver injury in
      mice.
AB  - Liver injury is an important cause of serious liver disease and is characterized
      by inflammatory and oxidative responses. Esculin, a coumarinic derivative found
      in Aesculus hippocastanum L., has been shown to exhibit anti-inflammatory and
      anti-oxidative effects. Here, we investigated the effects and molecular mechanism
      of esculin on Lipopolysaccharide/D-Galactosamine (LPS/D-Gal)-induced acute liver
      injury. A mouse model for acute liver injury was induced by intraperitoneal
      injection with D-Gal and LPS, and was assessed by histology, and serum
      transaminase analyses. The results showed that esculin significantly reduced the
      pathological symptoms of acute liver injury, as well as serum AST and ALT levels.
      LPS/D-Gal-induced liver myeloperoxidase (MPO) activity and malondialdehyde (MDA)
      content were also suppressed by esculin. Furthermore, LPS/D-Gal-induced liver
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta)
      production were attenuated by esculin. Our data demonstrate that esculin can
      inhibit nuclear factor kappa B (NF-kappaB) activation as well as increase nuclear
      factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. In
      conclusion, this paper demonstrates that esculin protects liver injury induced by
      LPS/D-Gal via inhibiting inflammatory and oxidative responses.

PMID- 30290267
TI  - Endophytic entomopathogenic fungi enhance the growth of Phaseolus vulgaris L.
      (Fabaceae) and negatively affect the development and reproduction of Tetranychus
      urticae Koch (Acari: Tetranychidae).
AB  - Entomopathogenic fungi (EPF) have primarily been applied as an inundative
      approach to manage pests. However, in recent decade multifunctional role of EPF
      have been documented which provide multiple benefits to host plants when
      colonized as an endophyte. In this study five fungal isolates from the genus
      Beauveria (three), Isaria (one) and Lecanicillium (one) were evaluated for their
      ability to colonize common bean, Phaseolus vulgaris and to assess their effects
      in planta on plant growth promotion and possible negative effects on the two
      spotted spider mites, Tetranychus urticae. All the tested isolates in this study
      were able to endophytically colonize root, stem and even leaves of inoculated
      plants examined at 7 and 14 days post inoculation, indicating the systemic
      colonization of EPF. Colonized plants showed increased plant heights, fresh shoot
      and root weights compared to plants without inoculation. Survivorship of T.
      urticae significantly differed among the treatments with higher survival
      probability in control plants. Significant reduction in larval development, adult
      longevity and female fecundity of spider mites were observed when fed on treated
      plants compared to control plants. The negative effects were found to be carried
      over the second generation fed on fresh plants. Overall, our results show (i) the
      positive effects of fungal endophytes on plant growth, (ii) reduction in
      population growth rate and (iii) negative effects of endophytes on growth and
      reproduction of spider mites in successive generations. The study presents
      reports on the endophytic management of plant-feeding mites and highlights the
      possibility of utilizing entomopathogenic fungal endophytes in the integrated
      pest management program.

PMID- 30290268
TI  - Effects of Christensenella minuta lipopolysaccharide on RAW 264.7 macrophages
      activation.
AB  - Christensenella minuta (C. minuta) is a gram-negative gastrointestinal bacterium
      associated with weight loss. However, recent studies have shown that C. minuta
      might be a potential pathogen and thus limited its application in the control of
      obesity. Research into the genetic characteristics and pathogenicity of C. minuta
      remain elusive. As a major virulence factor of gram-negative bacteria,
      lipopolysaccharide (LPS) can induce various diseases. In this study, we report
      the complete genome sequence of C. minuta and have also identified some genes
      related to LPS biosynthesis. The structure of C. minuta LPS, detected by SDS
      PAGE, was different from that of Escherichia coli (E. coli) LPS. The incubation
      of RAW 264.7 macrophages with C. minuta LPS resulted in lower levels of cellular
      proliferation, phagocytosis and nuclear factor-kappa B (NF-kappaB) activation as
      compared to incubation with E. coli LPS. Furthermore, the expression of pro
      inflammatory cytokines, as well as nitric oxide and reactive oxygen species
      production, was induced in C. minuta LPS-treated cells but to a much lower extent
      than that by E. coli LPS. These findings show that C. minuta LPS acts as a weak
      agonist for RAW 264.7 macrophages and can only trigger a weak inflammatory
      response through the NF-kappaB signalling pathway. In conclusion, these results
      suggest that the toxicity of C. minuta LPS is significantly attenuated due to its
      atypical structure and weak agonist activity for RAW 264.7 macrophages.

PMID- 30290269
TI  - Molecular docking, and anti-biofilm activity of gold-complexed sulfonamides on
      Pseudomonas aeruginosa.
AB  - The antibacterial activity of sulfadiazine Au-PPh3, sulfadiazine Ph2P-Au-Au-PPh2,
      sulfamethoxazole Au-PPh3, sulfamethoxazole Ph2P-Au-Au-PPh2, sulfamethoxazole Au
      PPh3 were tested against Pseudomonas aeruginosa. The antibacterial activity of
      sulfonamide was tested against P. aeruginosa through the MIC assay, quantitative
      analysis of biofilm inhibition and observation of biofilm formation with
      fluorescence microscopy. Besides, the compounds presented remarkable inhibition
      of P. aeruginosa biofilm formation. Furthermore, molecular docking was performed
      to identify the key structural features of these compounds with the binding site
      of the LasR receptor.

PMID- 30290270
TI  - Single-copy expression of an amyotrophic lateral sclerosis-linked TDP-43 mutation
      (M337V) in BAC transgenic mice leads to altered stress granule dynamics and
      progressive motor dysfunction.
AB  - Mutations in the gene encoding the RNA-binding protein TDP-43 cause amyotrophic
      lateral sclerosis (ALS), clinically and pathologically indistinguishable from the
      majority of 'sporadic' cases of ALS, establishing altered TDP-43 function and
      distribution as a primary mechanism of neurodegeneration. Transgenic mouse models
      in which TDP-43 is overexpressed only partially recapitulate the key cellular
      pathology of human ALS, but may also lead to non-specific toxicity. To avoid the
      potentially confounding effects of overexpression, and to maintain regulated
      spatio-temporal and cell-specific expression, we generated mice in which an 80 kb
      genomic fragment containing the intact human TDP-43 locus (either TDP-43WT or TDP
      43M337V) and its regulatory regions was integrated into the Rosa26
      (Gt(ROSA26)Sor) locus in a single copy. At 3 months of age, TDP-43M337V mice are
      phenotypically normal but by around 6 months develop progressive motor function
      deficits associated with loss of neuromuscular junction integrity, leading to a
      reduced lifespan. RNA sequencing shows that widespread mis-splicing is absent
      prior to the development of a motor phenotype, though differential expression
      analysis reveals a distinct transcriptional profile in pre-symptomatic TDP
      43M337V spinal cords. Despite the presence of clear motor abnormalities, there
      was no evidence of TDP-43 cytoplasmic aggregation in vivo at any timepoint. In
      primary embryonic spinal motor neurons and in embryonic stem cell (ESC)-derived
      motor neurons, mutant TDP-43 undergoes cytoplasmic mislocalisation, and is
      associated with altered stress granule assembly and dynamics. Overall, this mouse
      model provides evidence that ALS may arise through acquired TDP-43 toxicity
      associated with defective stress granule function. The normal phenotype until 6
      months of age can facilitate the study of early pathways underlying ALS.

PMID- 30290271
TI  - Wwox deletion leads to reduced GABA-ergic inhibitory interneuron numbers and
      activation of microglia and astrocytes in mouse hippocampus.
AB  - The association of WW domain-containing oxidoreductase WWOX gene loss of function
      with central nervous system (CNS) related pathologies is well documented. These
      include spinocerebellar ataxia, epilepsy and mental retardation (SCAR12, OMIM:
      614322) and early infantile epileptic encephalopathy (EIEE28, OMIM: 616211)
      syndromes. However, there is complete lack of understanding of the
      pathophysiological mechanisms at play. In this study, using a Wwox knockout (Wwox
      KO) mouse model (2 weeks old, both sexes) and stereological studies we observe
      that Wwox deletion leads to a significant reduction in the number of hippocampal
      GABA-ergic (gamma-aminobutyric acid) interneurons. Wwox KO mice displayed
      significantly reduced numbers of calcium-binding protein parvalbumin (PV) and
      neuropeptide Y (NPY) expressing interneurons in different subfields of the
      hippocampus in comparison to Wwox wild-type (WT) mice. We also detected decreased
      levels of Glutamic Acid Decarboxylase protein isoforms GAD65/67 expression in
      Wwox null hippocampi suggesting lower levels of GABA synthesis. In addition, Wwox
      deficiency was associated with signs of neuroinflammation such as evidence of
      activated microglia, astrogliosis, and overexpression of inflammatory cytokines
      Tnf-a and Il6. We also performed comparative transcriptome-wide expression
      analyses of neural stem cells grown as neurospheres from hippocampi of Wwox KO
      and WT mice thus identifying 283 genes significantly dysregulated in their
      expression. Functional annotation of transcriptome profiling differences
      identified 'neurological disease' and 'CNS development related functions' to be
      significantly enriched. Several epilepsy-related genes were found differentially
      expressed in Wwox KO neurospheres. This study provides the first genotype
      phenotype observations as well as potential mechanistic clues associated with
      Wwox loss of function in the brain.

PMID- 30290272
TI  - Multiple recycling routes: Canonical vs. non-canonical mitophagy in the heart.
AB  - The heart is composed of cardiomyocytes that require large amounts of energy to
      sustain contraction. Mitochondria are distinctive organelles of bacterial origin
      that generate most of the energy for the heart via oxidative phosphorylation. To
      ensure a healthy population of mitochondria that efficiently produce ATP,
      myocytes quickly eliminate any unhealthy or unwanted mitochondria via a process
      known as mitochondrial autophagy, or mitophagy. It is especially important to
      selectively remove damaged or aged mitochondria since they can become excessive
      producers of reactive oxygen species and release pro-death proteins. Because this
      is such a crucial cellular process, cells have several mechanisms in place to
      deal with potentially harmful mitochondria. Here, we review the various pathways
      identified to date and how they are regulated. We also discuss the importance of
      these canonical and non-canonical pathways in the heart and their link to
      cardiovascular health, disease and aging.

PMID- 30290273
TI  - C-terminal truncation exacerbates the aggregation and cytotoxicity of alpha
      Synuclein: A vicious cycle in Parkinson's disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disease which usually
      associates with neuroinflammation. The main pathological characteristics of PD
      are dopaminergic neurons death and the presence of Lewy bodies which are composed
      of aggregated alpha-synuclein (alpha-Syn). Truncated forms of alpha-Syn are found
      in the brain of PD patients, and account for 10-30% of total synuclein in Lewy
      bodies. Caspase-1, which plays an important role in neuroinflammation, cleaves
      full-length alpha-Syn (alpha-Syn FL) to generate a C-terminus 19-residues
      truncated alpha-Syn (alpha-Syn121). However, the role of truncated alpha-Syn in
      the onset and/or pathogenesis of PD is unclear. Here, we used alpha-Syn121 as a
      model to explore its aggregation, membrane disruption and cytotoxicity
      properties. Compared with alpha-Syn FL, alpha-Syn121 aggregated at an accelerated
      rate, and formed amorphous aggregates rich in random coil structures rather than
      beta-sheet-rich linear fibrils formed by alpha-Syn FL. Importantly, higher
      cytotoxicity with lower membrane disruption capacity was found for alpha-Syn121
      aggregates. Furthermore, alpha-Syn121 aggregates could activate the apoptosis
      signaling pathway and stimulate the caspase-1-mediated cleavage of alpha-Syn FL
      to generate alpha-Syn121, which as a result leading to increased levels of
      endogenous alpha-Syn121 and intracellular S129 phosphorylated alpha-Syn
      inclusions. Together, our data suggests a hidden vicious cycle in PD that alpha
      Syn121 rapidly forms amorphous aggregates, which activate caspase-1 to cleave
      alpha-Syn FL and generate more alpha-Syn121, and this cycle may contribute to the
      onset and/or pathogenesis of PD.

PMID- 30290274
TI  - Asthma alleviates obesity in males through regulating metabolism and energy
      expenditure.
AB  - Many epidemiological studies suggested a correlation between obesity and asthma.
      However, little is known about the molecular details explaining this correlation.
      Here, we show that asthma decreased body weight of asthmatic male mice fed with
      high fat diet via increasing energy expenditure and insulin sensitivity. The
      increase of energy expenditure was mainly due to upregulation of pAMPK and Sirt1.
      The activation of AMPK/Sirt1/PGC1alpha signaling promoted the expression of the
      thermogenic genes like ucp1, PRDM16, cidea, Elovl3, PPARalpha, which occurred in
      brown adipocyte tissue and subcutaneous white adipose tissue. Besides, by
      activating IL33/ILC2/AAMac pathway in subcutaneous white adipose tissue, asthma
      promoted subcutaneous white adipose tissue into beige fat. In addition, insulin
      sensitivity was improved in the asthmatic male mice by decreasing the expression
      of G6Pase in the liver, which was recapitulated in HepG2. In human, we found that
      Body Mass Index (BMI) and waist circumference were significantly lower in males
      suffering asthma compared with the control in the National Health and Nutrition
      Examination Survey (NHANES) cohort. These data together suggest asthma in males
      decreases obesity by improving the metabolism function of brown and subcutaneous
      adipose tissue, and decreasing insulin resistant in the liver.

PMID- 30290275
TI  - A web-based program to improve treatment adherence in patients with type 2
      diabetes: Development and study protocol.
AB  - BACKGROUND: Many patients with type 2 diabetes mellitus (T2DM) sub-optimally
      adhere to core treatment recommendations, such as healthy diets, sufficient
      physical activity and pharmacological support. This paper describes the
      development of the web-based computer-tailored program My Diabetes Profile (MDP),
      incorporating identified success factors of web-based interventions, and the
      protocol for testing the effectiveness of this program in a randomized
      multicentre trial. METHODS: Formative research - including the input of a program
      committee, qualitative and quantitative studies with patients and health
      professionals and a literature search - yielded input for the development of the
      MDP program. MDP provides video and text tailored advice, based on determinants
      and salient beliefs derived from the I-Change Model, on decreasing unhealthy
      snack intake, increasing physical activity, and improving adherence to both oral
      blood glucose lowering drugs and self-administered insulin therapy. Patients with
      T2DM recruited by practice nurses and diabetes nurses across the Netherlands fill
      in online questionnaires at baseline and six-months follow-up. Participants are
      randomized on patient level to the intervention group (access to the MDP program)
      or control group (receiving care as usual). DISCUSSION: The formative research
      using co-creation principles proved essential in the development of the MDP
      program and involved various disciplines in T2DM management including target
      group representatives. Co-creation revealed clearly that patients needed short
      and attractive messages. Consequently, a mix of video and short text messages
      were chosen for the ultimate program format. Pilot testing was useful to further
      shape the program to needs of patients and professionals. TRIAL REGISTRATION:
      Dutch Trial Register NTR6840; Archived program website:
      http://www.webcitation.org/6xXz01S7X.

PMID- 30290276
TI  - Mobile health intervention for self-management of adolescent chronic pain (WebMAP
      mobile): Protocol for a hybrid effectiveness-implementation cluster randomized
      controlled trial.
AB  - INTRODUCTION: Approximately 5-8% of children report severe chronic pain and
      disability. Although evidence supports pain-self management as effective for
      reducing pain and disability, most youth do not have access to psychological
      intervention. Our prior studies demonstrate that an existing internet-delivered
      pain self-management program (WebMAP) can reduce barriers to care, is feasible,
      acceptable, and is effective in reducing pain-related disability in youth with
      chronic pain. The current trial seeks to: 1) determine the effectiveness of a
      mobile app version of WebMAP for improving patient pain-related outcomes, and 2)
      evaluate a novel implementation strategy to maximize the public health impact of
      the intervention including the determination of adoption, reach, and
      sustainability of WebMAP in specialty clinics serving children with chronic pain
      in the United States. METHODS: This hybrid effectiveness-implementation cluster
      randomized controlled trial employs a stepped wedge design in which the WebMAP
      mobile intervention is sequentially implemented in 8 specialty pain clinics
      following a usual care period. This trial aims to enroll a minimum of 120 youth
      (ages 10-17) who have chronic pain. Outcome analyses will determine effectiveness
      of treatment on adolescent pain-related outcomes as well as public health impact
      via reach, adoption, implementation, and maintenance. CONCLUSIONS: This trial
      examines an innovative approach to evaluate a technology-delivered pain self
      management program for youth with chronic pain. Findings are expected to yield a
      strategic approach for delivering a digital pain management program for youth
      with chronic pain that can be sustained in clinical settings. Clinical Trial
      Registration #: NCT03332563.

PMID- 30290277
TI  - A randomised trial of real-time video counselling for smoking cessation in
      regional and remote locations: study protocol.
AB  - BACKGROUND: Real-time video communication technology (e.g. Skype) may be an
      effective mode for delivering smoking cessation treatment to regional and remote
      residents. This randomised trial examines the effectiveness of real-time video
      counselling compared to: 1) telephone counselling; and 2) written materials
      (control) in achieving smoking abstinence in regional and remote residents.
      DESIGN: A three-arm, parallel group, randomised trial will be conducted with
      smokers residing in regional and remote areas of New South Wales, Australia.
      Potential participants will complete an online screening survey and if eligible
      an online baseline survey. Participants will be randomly allocated into: 1) real
      time video counselling; 2) telephone counselling; or 3) written materials
      (control). In the video counselling intervention an advisor will deliver up to
      six video sessions (e.g. via Skype) to participants. Those who nominate a quit
      date within a month during the initial video session will be offered sessions on
      the quit date, 3-, 7-, 14- and 30-days after the quit date. Those not ready to
      set a quit date within a month during the initial video session will be offered
      sessions 2-, 4- and 6-weeks later. Other than delivery mode, the video
      counselling and telephone counselling will be identical in content and callback
      schedules. Control group participants will be mailed one-off written materials.
      Follow-up surveys will occur at 4-months, 7-months and 13-months post-baseline.
      The primary outcome will be 7-day point prevalence abstinence at 13-months post
      baseline. DISCUSSION: Real-time video counselling may be an effective strategy
      for smoking cessation that could be integrated into quitlines globally.

PMID- 30290278
TI  - Tardiness of starts of surgical cases is not substantively greater when the
      preceding surgeon in an operating room is of a different versus the same
      specialty.
AB  - STUDY OBJECTIVE: Switching from one specialty to another increases mean turnover
      times (i.e., interval between the exit and entrance of consecutive patients in an
      operating room [OR]). We estimate the effect on the mean tardiness of to-follow
      surgeons from following another surgeon of a different versus same specialty.
      Tardiness of a case's start time refers to the number of minutes the patient
      enters the OR later than scheduled; tardiness is 0 min if the patient enters
      early. Tardiness cause surgeon waiting. There are multiple causes of tardiness,
      but, most often, the preceding case(s) took longer than estimated. DESIGN: 10
      year historical cohort study with all surgical cases performed during regular
      workdays. SETTING: Large teaching hospital. MEASUREMENTS: Estimated OR end times
      were calculated using a Bayesian method. Because tardiness is influenced by the
      estimated case start time (i.e., later starting cases have greater tardiness),
      tardiness values were adjusted to a 12 noon start time for the 2nd surgeon. MAIN
      RESULTS: The cases of to-follow surgeons in ORs had mean tardiness of 45.1 (SE
      0.6) min. When the to-follow surgeon in the OR was of a different versus the same
      specialty from the first surgeon, the mean turnover time was 7.3 (0.4) min longer
      (P < 0.00001). However, the mean tardiness was not significantly affected (0.1
      min, 95% confidence interval [CI] -2.7 to 3.0 min; P = 0.93). In comparison, if
      one or more of the preceding cases in an OR was an add-on case, the increase in
      mean tardiness was 35 min (95% CI 28 to 43 min; P < 0.00001). CONCLUSIONS: OR
      managers can assure surgeons with afternoon starts that following a surgeon of a
      different specialty generally will not increase their waiting time. Case
      scheduling should focus on reducing over-utilized OR time and thus the hours that
      anesthesiologists and nurses work late.

PMID- 30290279
TI  - Anesthetic challenges in a case of Klippel-Trenaunay Syndrome with severe
      anaemia.

PMID- 30290280
TI  - Synthesis, molecular docking and inhibition studies of novel 3-N-aryl substituted
      2-heteroarylchromones targeting microtubule affinity regulating kinase 4
      inhibitors.
AB  - A series of 3-N-aryl substituted-2-heteroarylchromones was efficiently
      synthesized via Pd-mediated oxidative coupling under the influence of hetero
      atoms neighboring group participation. Synthesized molecules were evaluated
      against human microtubule affinity regulating kinase 4 (MARK4) enzyme inhibitors,
      a recently identified anti-cancer drug target. Among 21 synthesized molecules,
      compounds 2, 3, and 14 exhibited excellent in vitro inhibitory effect against
      MARK4 with IC50 value (50% of ATPase activity) at 2.12 +/- 0.22 MUM, 1.98 +/-
      0.34 MUM and 5.56 +/- 0.42 MUM respectively. The fluorescence binding and dot
      blot assay of these compounds were found in MUM range, indicating a better
      binding affinity. In vitro study of these compounds against cancerous cells (MCF
      7 and HepG2) inhibited the cell viability, induced apoptosis and lowered the tau
      phosphorylation. Cell viability studies of compounds 2, 3, and 14 showed
      inhibition of cancerous cells growth with IC50 values of 3.22 +/- 0.42, 4.32 +/-
      0.23 MUM and 16.22 +/- 1.33 MUM for human breast cancer cells (MCF-7) and 6.45 +/
      1.12, 5.22 +/- 0.72 MUM and 19.12 +/- 1.43 MUM for human liver carcinoma cells
      (HepG2) respectively. ROS quantification of these compounds showed oxidative
      stress to cancerous cells and molecular docking study showed hydrogen bonding,
      charge or polar and van der Waals interactions with the active site residues of
      MARK4. Owning to high binding fit nicely in the active site, offering the
      possibilities to be used as novel therapeutic molecules in the drug discovery
      against MARK4-related diseases.

PMID- 30290281
TI  - Is recovery from ankle sprains negatively affected by obesity?
AB  - OBJECTIVE: Ankle sprains are common injuries that may lead to long-term
      morbidity. Individuals with obesity are at increased risk for ankle sprains;
      however, prognostic associations between body mass index (BMI) and recovery are
      less well understood. This study investigated whether BMI status affects recovery
      from ankle sprains. METHODS: We included individuals>=16 years old with grade 1
      or 2 ankle sprains who sought emergency department treatment in Kingston,
      Ontario, Canada. Height in centimeters and weight in kilograms were measured at
      baseline by using a height rod and a standard medical column scale, respectively.
      BMI was calculated and categorized as non-overweight,<25.0kg/m2; overweight, 25.0
      29.9kg/m2; and obese,>=30kg/m2. Recovery was assessed at 1, 3 and 6 months post
      injury by the Foot and Ankle Outcome Score (FAOS). Continuous FAOS and binary
      recovery status were compared by BMI group at each assessment using a repeated
      measures linear mixed effects model and logistic regression, respectively.
      RESULTS: In total, 504 individuals were recruited and 6-month follow-up data were
      collected for 80%. We observed no significant differences in recovery at 1 and 3
      months post-injury. At 6 months, between 53% and 66% of the participants were
      considered to have recovered according to the FAOS. The mean difference in
      unadjusted FAOS between participants classified as obese and non-overweight was 
      23.02 (95% confidence interval, -38.99 to -7.05) but decreased after adjusting
      for confounders. The odds ratio for recovery was 0.60 (0.37-0.97) before
      adjustment and 0.74 (0.43-1.29) after adjustment. Six-month recovery was
      significantly lower for participants with obesity than non-overweight
      participants on the FAOS Pain and Function in Daily Living subscales but were not
      clinically meaningful. CONCLUSIONS: All BMI groups showed improvements from ankle
      sprain over time. However, at 6 months, a sizeable proportion of the participants
      had not fully recovered particularly among individuals classified as obese. The
      findings suggest that individuals with obesity may benefit from specialized
      interventions focused on symptom management and functional activity.

PMID- 30290282
TI  - Orthopaedic surgery for patients with central nervous system lesions: Concepts
      and techniques.
AB  - Since ancient times, the aim of orthopedic surgery has been to correct limb and
      joint deformities, including those resulting from central nervous system lesions.
      Recent developments in the treatment of spasticity have led to changes in
      concepts and management strategies. The increase in life expectancy has increased
      the functional needs of patients. Orthopedic surgery, along with treatments for
      spasticity, improves the functional capacity of patients with neuro-orthopaedic
      disorders, improving their autonomy. In this paper, we describe key moments in
      the history of orthopedic surgery regarding the treatment of patients with
      central nervous system lesions, from poliomyelitis to stroke-related hemiplegia,
      from the limbs to the spine, and from contractures to heterotopic ossification. A
      synthesis of the current surgical techniques is then provided, and the importance
      of multidisciplinary evaluation and management is highlighted, along with
      indications for medical, rehabilitation and surgical treatments and their
      combinations. We explain why it is essential to consider patients' expectations
      and to set achievable goals, particularly before surgery, which is by nature
      irreversible. More recently, specialized surgical teams have begun to favor the
      use of soft-tissue techniques over bony and joint procedures, except for spinal
      disorders. We highlight that orthopedic surgery is no longer the end-point of
      treatment. For example, lengthening a contractured muscle improves the balance
      around a joint, improving mobility and stability but may be only part of the
      problem. Further medical treatment and rehabilitation, or additional surgery, are
      often necessary to continue to improve the function of the limb. Despite the
      recognized effectiveness of orthopedic surgery for neuro-orthopedic disorders,
      few studies have formally evaluated them. Hence, there is a need for research to
      provide evidence to support orthopedic surgery for treating neuro-orthopedic
      disorders.

PMID- 30290283
TI  - Physical activity level and association with behavioral factors in knee
      osteoarthritis.
AB  - BACKGROUND: The effects of physical activity (PA) in disease prevention and
      therapy have well-known effects on lower-limb osteoarthritis (OA), decreasing
      pain and improving function. OBJECTIVE: We aimed to describe the level and
      factors affecting PA practices of people with knee OA. DESIGN: Prospective
      epidemiological study. SETTING: In all, 548 people with knee OA were interviewed
      by use of self-administered anonymous questionnaires. MAIN OUTCOME MEASUREMENT:
      The main outcome was physical activity level evaluated by the International
      physical activity questionnaire (IPAQ) (short version). Secondary outcomes
      included sociodemographic and clinical data, comorbidities, and barriers to and
      facilitators of practicing regular PA evaluated by 24 specific elements. RESULTS:
      The mean (SD) age of the study population was 67.6 (7.9) years; 73.9% were women
      and 30.9% had obesity (mean [SD] body mass index [BMI] 28.2 [5.7] kg/m2). Multi
      joint OA affected 92% of the population, and 71.6% had comorbidities. The mean
      (SD) visual analog scale score for pain intensity was 4.5/10 (2.5), which was
      51.4% better than the patient acceptable symptom state (PASS). The mean (SD)
      Western Ontario and McMaster Universities Osteoarthritis Index function score was
      36.6/100 (20.7), which was 57.5% better than the PASS. In total, 67% of patients
      used analgesics, half of them at least once a week. According to the IPAQ, 42.6%
      of patients reported high, 38.6% moderate, and 18.8% low PA level; the median
      IPAQ total activity score was 2628 metabolic equivalent of task (MET)-min/week
      and time spent sitting was 257.1min/day. Only one third of participants received
      non-pharmacological treatment corresponding to the latest recommendations.
      Variables significantly related to inactive or minimally active PA levels were
      BMI (P=0.0294), sex (P=0.0008), and biomedical barriers, related to self-efficacy
      (P=0.0118). CONCLUSIONS: The OA study population was less active, more sedentary,
      and had more comorbidities and more barriers to PA practice than the overall
      population.

PMID- 30290284
TI  - Informal caregiving and diurnal patterns of salivary cortisol: Results from the
      Whitehall II cohort study.
AB  - The objective was to investigate the relationship between various aspects of
      informal caregiving and diurnal patterns of salivary cortisol, with special
      attention to the moderating effect of sex and work status. The study population
      was composed of 3727 men and women from the British Whitehall II study. Salivary
      cortisol was measured six times during a weekday. Aspects of caregiving included
      the relationship of caregiver to recipient, weekly hours of caregiving, and
      length of caregiving. Diurnal cortisol profiles were assessed using the cortisol
      awakening response (CAR) and diurnal cortisol slopes. Results showed that men,
      but not women, providing informal care had a blunted CAR compared with non
      caregivers (PInteraction = 0.03). Furthermore, we found a dose-response
      relationship showing that more weekly hours of informal care was associated with
      a more blunted CAR for men (Ptrend = 0.03). Also, the blunted CAR for men was
      especially pronounced in short-term caregivers and those in paid work. In women,
      the steepest cortisol slope was seen among those in paid work who provided
      informal care (PInteraction = 0.01). To conclude, we found different cortisol
      profiles in male and female informal caregivers. Male caregivers had a blunted
      CAR, which has previously been associated with chronic stress and burnout. Future
      research should investigate whether results are generalizable beyond UK citizens
      with a working history in the civil service.

PMID- 30290285
TI  - Parasitaemia and parasitic load are limited targets of the aetiological treatment
      to control the progression of cardiac fibrosis and chronic cardiomyopathy in
      Trypanosoma cruzi-infected dogs.
AB  - It is still unclear whether the progression of acute to chronic Chagas
      cardiomyopathy is predominantly associated with the limited efficacy of
      aetiological chemotherapy, or with the pharmacological resistance profiles and
      pathogenicity of specific Trypanosoma cruzi strains. Thus, we tested the
      hypothesis that parasitic load could be a limited target of aetiological
      chemotherapy to prevent chronic cardiomyopathy in dogs infected by different T.
      cruzi strains. Animals were infected with benznidazole-susceptible (Berenice-78)
      and -resistant (VL-10 and AAS) strains of T. cruzi. A quantitative real-time PCR
      strategy was developed to comparatively quantify the parasite load of the three
      different strains using a single standard curve. For dogs infected with the VL-10
      strain, benznidazole treatment reduced cardiac parasitism during the acute phase
      of infection. However, similar parasite load and collagen deposition were
      detected in the myocardium of treated and untreated animals in the chronic phase
      of the infection. In animals infected with the AAS strain, benznidazole reduced
      parasite load, myocarditis and type III collagen deposition in the acute phase.
      However, increased type III collagen deposition was verified in the chronic
      phase. Dogs infected with the Berenice-78 strain showed a parasitological cure
      and no evidence of myocardial fibrosis. Parasitic load and cardiac fibrosis
      presented no correlation in acute or chronic phases of T. cruzi infection. Our
      findings in a canine model of Chagas disease suggest that parasite burden is a
      limited predictor for disease progression after treatment and show that
      benznidazole, although not inducing parasitological cure, is able to prevent
      total fibrosis in the early stages of infection, as well as complete prevention
      of cardiac damage when it eliminates parasites at the onset of infection.

PMID- 30290286
TI  - Network abnormalities in generalized anxiety pervade beyond the amygdala-pre
      frontal cortex circuit: Insights from graph theory.
AB  - Generalized anxiety disorder (GAD) has excessive anxiety and uncontrollable worry
      as core symptoms. Abnormal cerebral functioning underpins the expression and
      perhaps pathogenesis of GAD:. Studies implicate impaired communication between
      the amygdala and the pre-frontal cortex (PFC). Our aim was to longitudinally
      investigate whether such network abnormalities are spatially restricted to this
      circuit or if the integrity of functional brain networks is globally disrupted in
      GAD. We acquired resting-state functional magnetic resonance imaging data from 16
      GAD patients and 16 matched controls at baseline and after 1 year. Using network
      modeling and graph-theory, whole-brain connectivity was characterized from local
      and global perspectives. Overall lower global efficiency, indicating sub-optimal
      brain-wide organization and integration, was present in patients with GAD
      compared to controls. The amygdala and midline cortices showed higher betweenness
      centrality, reflecting functional dominance of these brain structures. Third,
      lower betweenness centrality and lower degree emerged for PFC, suggesting
      weakened inhibitory control. Overall, network organization showed impairments
      consistent with neurobiological models of GAD (involving amygdala, PFC, and
      cingulate cortex) and further pointed to an involvement of temporal regions. Such
      impairments tended to progress over time and predict anxiety symptoms. A graph
      analytic approach represents a powerful approach to deepen our understanding of
      GAD.

PMID- 30290287
TI  - MYC Amplification as a Potential Mechanism of Primary Resistance to Crizotinib in
      ALK-Rearranged Non-Small Cell Lung Cancer: A Brief Report.
AB  - INTRODUCTION: Translocations of the anaplastic lymphoma kinase (ALK) can be
      effectively targeted in advanced non-small cell lung cancer by ALK-TKI inhibitors
      including Crizotinib. However, the development of acquired resistance often
      limits the duration of these therapies. While several mechanisms of secondary
      resistance have been already identified, little is known about molecular
      determinants of primary resistance. In our brief report we investigated the tumor
      molecular profile of a patient who failed to respond to Crizotinib. METHODS:
      Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS)
      were run on tumor specimen as well as search and characterization of circulating
      tumor cells (CTCs) in the blood. Confirmation of clinical findings was achieved
      using a translational cell-line in vitro model. RESULTS: We identified the
      amplification of MYC as a potential new mechanism of primary resistance to ALK
      inhibition. Human EML4-ALK rearranged cells infected with a lentiviral vector
      carrying full-length human MYC cDNA were treated in vitro with crizotinib and
      alectinib. Overexpression of MYC overexpression was associated with a reduced
      sensitivity to both ALK-inhibitors. MYC-overexpressing clones displayed also
      increased levels of both cyclin D and E and their growth was reduced by using
      Cdk4/6 inhibitors such as Palbociclib. CONCLUSIONS: We postulate that the MYC
      gene may be implicated in the mechanism of primary resistance to ALK inhibitors.
      We also suggest potential MYC-directed inhibition strategies to overcome primary
      resistance in advanced ALK-rearranged NSCLC.

PMID- 30290288
TI  - Political cycles in physician employment: A case of Japanese local public
      hospitals.
AB  - A shortage of physicians in local public hospitals is often a heated political
      issue. When local politicians have the authority to intervene in the management
      of a public hospital, they may increase the employment of physicians during
      election years in order to alleviate the shortage. We test this hypothesis
      empirically using a census of city hospitals in Japan from 2002 to 2011 (N =
      4583). Our results support the hypothesis that the number of physicians increases
      in election years. This effect is stronger in cities with a greater population of
      elderly residents. We also find that physicians tend to come from university
      hospitals in the same region. Overall, this paper provides direct evidence of
      political intervention on physician employment.

PMID- 30290289
TI  - Design and baseline characteristics of the eValuation of ERTugliflozin effIcacy
      and Safety CardioVascular outcomes trial (VERTIS-CV).
AB  - BACKGROUND: Ertugliflozin is an inhibitor of sodium-glucose co-transporter-2
      (SGLT2), approved in the United States and European Union to improve glycemic
      control in adults with type 2 diabetes mellitus (T2DM). The VERTIS cardiovascular
      (CV) outcomes trial (NCT01986881) has a primary objective to demonstrate non
      inferiority of ertugliflozin versus placebo on major adverse CV events: time to
      the first event of CV death, nonfatal myocardial infarction, or nonfatal stroke.
      Secondary objectives are to demonstrate superiority of ertugliflozin versus
      placebo on time to: 1) the composite outcome of CV death or hospitalization for
      heart failure (HF); 2) CV death; and 3) the composite outcome of renal death,
      dialysis/transplant, or doubling of serum creatinine from baseline. METHODS:
      Patients >=40 years old with T2DM (HbA1c 7.0-10.5%) and established
      atherosclerotic cardiovascular disease (ASCVD) of the coronary, cerebral, and/or
      peripheral arterial systems, were randomized 1:1:1 to once daily double-blind
      placebo, ertugliflozin 5 mg or 15 mg added to existing therapy. RESULTS: 8246
      patients were randomized and 8238 received at least 1 dose of investigational
      product. Mean age was 64.4 years, 11.0% were >=75 years old, and mean diabetes
      duration was 12.9 years with screening HbA1c of 8.3%. At entry, coronary artery
      disease, cerebrovascular disease, and peripheral arterial disease were present in
      76.3%, 23.1%, and 18.8% of patients, respectively. HF was present in 23.1%, and
      Stage 3 kidney disease in 21.6% of patients. CONCLUSION: The results from the
      VERTIS-CV trial will define the CV and renal safety and efficacy of ertugliflozin
      in patients with T2DM and ASCVD.

PMID- 30290290
TI  - Countering clinical inertia in lipid management: Expert workshop summary.

PMID- 30290291
TI  - Opioid and cocaine use among primary care patients on buprenorphine-Self-report
      and urine drug tests.
AB  - BACKGROUND: Urine drug tests (UDTs) are recommended to monitor patients treated
      for opioid use disorder in primary care. The aims are to (1) estimate the
      frequency of self-report and UDT results of opioid and cocaine use and (2)
      evaluate the association between treatment time with non-disclosure of opioid or
      cocaine use and having a positive UDT. METHODS: We conducted a retrospective
      review of patients enrolled in a primary care-based buprenorphine program between
      January 2011-April 2013. We describe three clinical visits types: no disclosure
      of opioid/cocaine use and positive UDT; disclosure of opioid or cocaine use and a
      negative or positive UDT; and no disclosure of opioid or cocaine use and a
      negative UDT. We fit generalized estimating equations logistic regression models
      to evaluate whether treatment time is associated with non-disclosure of opioids
      or cocaine use and a positive UDT. RESULTS: Among all UDT results (n = 1755) from
      130 patients, 10% were positive for illicit opioids and 4% for cocaine. Among
      UDTs with illicit opioid or cocaine positive results, in 57% and 76% of these
      scenarios, the patient did not disclose. The odds of non-disclosure and having a
      positive UDT was higher in the first 180 days for opioids and 90 days for
      cocaine. CONCLUSION: Among primary care patients treated with buprenorphine, a
      small but substantial percentage of UDTs were cocaine or opioid positive. As
      treatment time increased, non-disclosure was less common but persisted even after
      six months. Among primary care patients treated with buprenorphine, UDTs
      contribute information to optimize clinical care.

PMID- 30290292
TI  - A combined experimental and density functional theory investigation of the
      hydrogen bonding of 2-cyclohexen-1-one and 3-methyl- 2-cyclohexen-1-one in
      solvents.
AB  - Hydrogen bonding is a weak chemical interaction widely existed in the variety of
      organic and biological molecules. As an important structural motif of pyrimidine
      bases, the solvent effect of the hydrogen bonding of 2-cyclohexen-1-one (CHO) and
      3-methyl- 2-cyclohexen-1-one (3MCHO) and its effect on the frequency shift of the
      CO stretching mode were investigated by using the FT-Raman and UV absorption
      spectra and density functional theory calculations. The electronic transitions
      associated with the UV absorptions in different solvents were calculated at B3LYP
      TD/6-31++G(d,p) level of theory and employing SCIPCM solvent model. The
      vibrational spectra of CHO and 3MCHO were assigned on the basis of the FT-Raman
      spectra in neat liquid and different solvents, the calculated vibrational spectra
      of monomer and CHO dimers, and the concentration dependent experiments of the
      band pair intensities. Hydrogen bonding energies of CHO-(H2O)n (n = 1,2) clusters
      were predicted. The results reveal that the CHO-(H2O)2 cluster and CHO monomer
      are respectively the major source of spectral observation in water and
      cyclohexane, while CHO dimmer and CHO monomer coexist in acetonitrile. The
      difference in the frequency of the nuC=O stretching mode between 3MCHO monomer
      and CHO monomer in cyclohexane were explored.

PMID- 30290293
TI  - Sex determination of silkworm pupae using VIS-NIR hyperspectral imaging combined
      with chemometrics.
AB  - To explore an accurate and non-destructive method to discriminate the sex of
      silkworm pupae, the visible and near-infrared (VIS-NIR) hyperspectral imaging
      (HSI) technique was employed in this paper. First, a total of 520 hyperspectral
      images of silkworm pupae of four species were captured using a push-broom HSI
      system in the spectral region of 363 nm to 1026 nm and then calibrated for
      reflectance. The mean spectral data were extracted from the region of interest
      (ROI). Second, five optimal wavelengths (403, 440, 505, 533, 721 nm) were
      selected by successive projection algorithm (SPA). Then gray-level co-occurrence
      matrix (GLCM) analysis was implemented on the 500 nm image. Finally, support
      vector machine (SVM) and radial basis function and neutral network (RBF-NN)
      models were established based on full spectra, textural data, spectral data and
      fusion data, respectively. The SVM and RBF-NN models using fusion data reached
      the most satisfactory performance with a high correct classification rate of
      98.75%. Furthermore, the built SVM model based on fusion data could be promoted
      to identify the sex of another two species of silkworm pupae with accuracy of 97%
      and 96%, indicating that HSI technology can be served as a new method to
      differentiate the sex of silkworm pupae.

PMID- 30290294
TI  - Interferon gamma and interleukin 8 gene polymorphisms in patients with hepatitis
      C virus related oral lichen planus.
AB  - OBJECTIVES: This study aimed to determine the association of rs2430561 and rs4073
      polymorphisms in the Interferon gamma (IFN-?) and Interleukin 8 (IL-8) genes,
      respectively, with hepatitis C virus-related oral lichen planus and disease
      severity. DESIGN: This is a case-control study. 60 subjects were equally divided
      into patients with and without oral lichen planus. They were further subdivided
      into hepatitis C virus seropositive and seronegative patients. All patients were
      genotyped for IFN-gamma rs2430561 thymine to adenine (T > A) and IL-8 rs4073
      adenine to thymine (A > T) polymorphisms. All patients with oral lichen planus
      had their lesions measured and documented using the Escudier scoring system.
      RESULTS: Disease activity was significantly higher in the "oral lichen
      planus/hepatitis C virus-positive" patients than in the "oral lichen
      planus/hepatitis C virus-negative" patients (P = 0.003). IFN-gamma rs2430561 T >
      A and IL-8 rs4073 A > T genotypes and allele frequencies were not associated with
      the oral lichen planus group or the normal group. Stratification of the two
      groups into HCV and non-HCV-infected patients or into erosive and non-erosive
      types revealed no significant associations. The "A-allele-containing" genotypes
      of IL-8 rs4073 A > T were significantly more prevalent in the patients with oral
      lichen planus than in those without. CONCLUSION: Hepatitis C virus infection is
      associated with the development of erosive oral lichen planus. The A-allele of IL
      8 rs4073 A > T may have a role in the development and progression of oral lichen
      planus.

PMID- 30290295
TI  - Erythromycin sensitivity across different taxa of marine phytoplankton. A novel
      approach to sensitivity of microalgae and the evolutionary history of the 23S
      gene.
AB  - Erythromycin has been recorded in coastal waters and could pose a severe threat
      to marine microbial life. Macrolides such as erythromycin may affect microalgae
      by inhibiting the pathways involved in protein synthesis. Toxicological testing
      of microalgae has proven to be a useful tool for the risk assessment of a
      substance affecting phytoplankton. Due to the controversial results concerning
      the sensitivity of microalgal species to erythromycin found in the literature,
      the goals of this work were, initially, to assess the erythromycin sensitivity of
      different species of marine microalgae from different and representative
      taxonomic groups; and, secondly, to examine whether the sensitivity to
      erythromycin could be explained by the differences in the phylogenetic evolution.
      We chose eight species: two green algae, four heterokonts, one haptophyte and one
      dinoflagellate, which were then exposed to erythromycin (0.1 to 10 mg L-1). Our
      results showed a wide range of sensitivities indicating that the biology of each
      species was primarily responsible for the variation observed. To test the second
      objective, we contrasted different ecotoxicological endpoints (growth, cellular
      properties and status of the photosynthetic apparatus) with the phylogenetic
      distribution [eukaryotic host (concatenated nuclear tree), evolutionary history
      of the chloroplast (16S tree), efficiency and repair of photosystem II (psbA
      tree), and the binding site of erythromycin (23S tree)] of the species. We found
      that the growth inhibition of microalgae as a toxicological endpoint was the
      endpoint best explained by the topology of the 23S rRNA gene tree when it was
      modelled following a non-stationary evolutionary process.

PMID- 30290296
TI  - Fabricating cauliflower-like and dumbbell-like Janus particles: Loading and
      simultaneous release of DOX and ibuprofen.
AB  - Most recent studies on Janus particles have concentrated on amphiphilic Janus
      particles. Herein, a facile and efficient method based on polymerization-induced
      phase separation is presented to fabricate Janus particles with different
      morphologies. Theses novel hydrophilic Janus particles with two distinct
      hydrophilic domains have been prepared by combination of distillation
      precipitation polymerization (DPP) and seeded emulsion polymerization.
      Crosslinked poly(2-hydroxyehtyl methacrylate) (PHEMA) cores were synthesized via
      DPP and used as seed particles. Also, methacrylic acid (MAA) was used as second
      hydrophilic monomer. Effect of feeding approach, and reaction medium were
      investigated on the morphology of fabricated composite particles. Different
      morphologies such as cauliflower-like, dumbbell-like, and core-shell toward
      cauliflower-like structures were obtained by varying feeding approach and
      polymerization medium. The morphology of resultant particles was observed by
      means of FE-SEM and TEM images and their particle sizes were confirmed by DLS.
      Fabricated composite particles were used to simultaneously carry both DOX and
      ibuprofen. Drug release studies showed that Janus particles can be used in
      loading and release of two drugs simultaneously. However, release behaviors of
      DOX and ibuprofen were different at different pH values. Also, release behavior
      was significantly affected by the structure of composite particles.

PMID- 30290297
TI  - ECG authentication system design incorporating a convolutional neural network and
      generalized S-Transformation.
AB  - Electrocardiogram (ECG) is gaining increased attention as a biometric method in a
      wide range of applications, such as access control and security/privacy
      requirements. The majority of reported investigations using the ECG biometric
      method are usually based on fiducial or nonfiducial methods, which are always
      accompanied by a series of issues, such as locating fiducial points accurately is
      difficult, feature selection is subjective, and classifiers are limited by the
      quantity and structure of data. This paper proposes a new biometric
      authentication system for human identification that uses ECG signals as a
      biometric trait and integrates a generalized S-transformation and a convolutional
      neural network (CNN). Specifically, we first introduce a blind segmentation
      strategy that effectively avoids difficult data-specific heartbeat recognition
      and segmentation techniques. Then, a generalized S-transformation is performed on
      the blind signal-processed ECG signal, capturing the ECG trajectory at each time
      point in the frequency domain. Next, the getframe technology is used to capture
      an image of the ECG trajectories and convert the one-dimensional signal to a two
      dimensional image, which serves as the input layer of the CNN, thus fully
      reflecting the changing trend in the ECG signal spectrum characteristics over a
      continuous period. Finally, the CNN is used for automatic discriminative feature
      learning and representations, which avoids a tedious feature extraction
      algorithm. In addition, considering the possible impact of ECG signals with
      different signal behaviors on identification, experiments are performed on three
      ECG databases with diverse features, comprising normal individuals, atrial
      fibrillation patients, and a noisy database, to evaluate the effectiveness of the
      proposed algorithm. Promising identification rates of 99%, 98%, and 99% were
      achieved, respectively. Thus, our proposed ECG authentication system can be
      effectively used for identity recognition under various conditions.

PMID- 30290298
TI  - Perfusion abnormality on three-dimensional arterial spin labeling with a 3T MR
      system in pediatric and adolescent patients with migraine.
AB  - PURPOSE: Few studies have assessed the prevalence of perfusion abnormality with
      migraine. This study aimed to determine the prevalence and topography of
      perfusion abnormality on three-dimensional (3D) arterial spin labeling (ASL) and
      assess the correlation between perfusion abnormality and clinical data in
      pediatric and adolescent patients with migraine. METHODS: Forty-nine consecutive
      pediatric and adolescent patients with migraine were enrolled, and they underwent
      3 T MRI, including 3D ASL. Perfusion abnormality on 3D ASL was qualitatively
      evaluated using a five-point grading system and was compared with non-ASL MR
      findings. In patients with perfusion abnormality, relative cerebral perfusion
      signal intensity (rCPS) was measured. Moreover, we compared clinical data and 3D
      ASL findings between patients with and those without perfusion abnormality.
      RESULTS: Of the 49 patients, 11 (22%) exhibited perfusion abnormality, and the
      occipital lobe was the most frequently involved (73%). One patient showed mild
      hyperperfusion (rCPS =2.474), and 10 showed hypoperfusion (mean rCPS = 0.405 +/-
      0.134). There was no abnormality on non-ASL MRI, except in one case. We found
      statistically significant differences in the presence of aura (P < .001), motor
      disabilities (P = .019), confusion (P = .004), hospitalization (P = .004),
      between patients with and those without perfusion abnormality. CONCLUSION: In
      pediatric and adolescent patients with migraine, 3D ASL shows a high prevalence
      of perfusion abnormality, especially in the occipital lobe. Patients with
      perfusion abnormality tend to show the specific clinical symptoms at disease
      onset and need hospitalization.

PMID- 30290299
TI  - Factors associated with Quitline and pharmacotherapy utilisation among low
      socioeconomic status smokers.
AB  - AIMS: To examine factors associated with Quitline and pharmacotherapy utilisation
      in low socioeconomic status (low-SES) smokers enrolled in a smoking cessation
      trial. METHODS: Baseline data was used from a large-scale smoking cessation
      randomised controlled trial (RCT). Logistic regression models were used to
      examine predictors of treatment utilisation prior to entering the RCT and
      perceived effectiveness of past and future use. RESULTS: A total of 1047 smokers
      consented and prior to enrolment 92% had previously tried to quit smoking, 86%
      had ever used quit support, 83% had used pharmacotherapy at least once and 38%
      had ever utilised Quitline. For those who had used pharmacotherapies, 71% used
      NRT, of which 21% had used dual NRT products. In the last 12-months, 27% utilised
      Quitline and 50% utilised NRT. Ever use of Quitline was negatively associated
      with self-efficacy to quit (OR: 0.80; 95% CI: 0.68, 0.94 p < .01) and positively
      associated with being diagnosed with a mental health condition (OR: 1.50; 95% CI:
      1.01, 2.25 p < .05). Recent use of NRT was positively associated with mental
      health condition (OR: 1.39; 95% CI: 1.02, 1.90 p < .05) and negatively associated
      with alcohol consumption (OR: 0.69; 95% CI: 0.52, 0.92 p < .01). CONCLUSION: Past
      use of Quitline and pharmacotherapy treatment was associated with self-efficacy
      to quit, sociodemographic variables, mental health conditions and alcohol
      consumption. Community-based strategies that target smoking, mental health and
      drug and alcohol problems may overcome some of the barriers that prevent low-SES
      populations from engaging with smoking cessation support.

PMID- 30290300
TI  - Very early drinking: Event history models predicting alcohol use initiation from
      age 4 to 11 years.
AB  - While it is not normative to initiate alcohol use prior to adolescence,
      substantial numbers of children do so. However, relatively little is known about
      the prevalence or predictors of alcohol initiation in childhood, compared to
      extensive research on adolescent initiation and alcohol use. The present study
      examines patterns and predictors of very early drinking initiation in childhood,
      focusing on child behavioral undercontrol and parent alcohol and drug use as time
      varying risk factors across childhood, independent of sociodemographic background
      variables. Event history analyses model and predict the age of alcohol initiation
      across ages 4 to 11 in the ongoing Millennium Cohort Study. Methodological
      strengths include the prospective design initiated in infancy (prior to any
      alcohol consumption), multiple reporters, and large representative sample of
      children and parents (n = 11,355). Key predictors are child behavioral
      undercontrol and parent alcohol and drug use assessed across childhood. Weighted
      results show that <2% of children had their first drink of alcohol prior to their
      8th birthday, rising to 13% by age 10-11 years. Odds of initiation are higher
      when parents rated children as behaviorally undercontrolled and when at least one
      parent in the household reported drinking alcohol and/or using illegal drugs,
      independent of sociodemographic group differences. Thus, an important minority
      initiated drinking during childhood, and there are key risk factors for early
      drinking. Increased focus on the epidemiology, etiology, and prevention of
      childhood drinking is needed.

PMID- 30290301
TI  - Childhood maltreatment and perceived stress in young adults: The role of emotion
      regulation strategies, self-efficacy, and resilience.
AB  - Childhood maltreatment has many deleterious outcomes; however, trait resilience
      as well as emotion regulation strategies, including suppression and reappraisal,
      may mediate between childhood maltreatment and later perceived stress. For this
      study, 267 college students (183 females and 84 males; M age = 19.77, SD = 2.29)
      completed self-report measures of parental psychological and physical
      maltreatment, parental emotion neglect, habitual use of suppression and
      reappraisal strategies, emotion regulation self-efficacy, trait resilience, and
      recent perceived stress. Analyses were conducted to investigate gender-specific
      associations. In females, both suppression and reappraisal mediated the
      relationship between maternal/paternal emotional neglect and perceived stress,
      and suppression also mediated the relationship between maternal psychological
      maltreatment and perceived stress. Trait resilience mediated the relationships of
      all three types of maternal maltreatment, paternal psychological maltreatment,
      and paternal emotional neglect with perceived stress in females. There were no
      significant mediation effects in males. Thus, interventions aiming at reducing
      perceived stress associated with maternal or paternal emotional neglect or
      maternal psychological maltreatment in women may benefit from targeting both
      suppression and reappraisal. Such interventions may also be enhanced by efforts
      to strengthen trait resilience.

PMID- 30290302
TI  - Hydroxycobalamin catalyzes the oxidation of diethyldithiocarbamate and increases
      its cytotoxicity independently of copper ions.
AB  - It is known that some metals (Cu, Zn, Cd, Au) markedly increase the toxic effect
      of thiocarbamates. It was shown in the present study that hydroxycobalamin (a
      form of vitamin B12, HOCbl), which incorporates cobalt, significantly enhances
      the cytotoxicity of diethyldithiocarbamate (DDC), decreasing its IC50 value in
      tumor cells three to five times. The addition of HOCbl to aqueous DDC solutions
      accelerated the reduction of oxygen. No hydrogen peroxide accumulation was
      observed in DDC + HOCbl solutions; however, catalase slowed down the oxygen
      reduction rate. Catalase as well as the antioxidants N-acetylcysteine (NAC) and
      glutathione (GSH) partially inhibited the cytotoxic effect of DDC + HOCbl,
      whereas ascorbate, pyruvate, and tiron, a scavenger of superoxide anion, had no
      cytoprotective effect. The administration of HOCbl into DDC solutions (> 1 mM)
      resulted in the formation of a crystalline precipitate, which was inhibited in
      the presence of GSH. The data of UV and NMR spectroscopy and HPLC and Mass
      Spectrometry (LC/MS) indicated that the main products of the reaction of DDC with
      HOCbl are disulfiram (DSF) and its oxidized forms, sulfones and sulfoxides. The
      increase in the cytotoxicity of DDC combined with HOCbl occurred both in the
      presence of Cu2+ in culture medium and in nominally Cu-free solutions, as well as
      in growth medium containing the copper chelator bathocuproine disulfonate (BCS).
      The results indicate that HOCbl accelerates the oxidation of DDC with the
      formation of DSF and its oxidized forms. Presumably, the main cause of the
      synergistic increase in the toxic effect of DDC + HOCbl is the formation of
      sulfones and sulfoxides of DSF.

PMID- 30290303
TI  - Microstructural brain changes track cognitive decline in mild cognitive
      impairment.
AB  - Improved characterization of the microstructural brain changes occurring in the
      early stages of Alzheimer's disease may permit more timely disease detection.
      This study examined how longitudinal change in brain microstructure relates to
      cognitive decline in aging and prodromal Alzheimer's disease. At baseline and two
      year follow-up, 29 healthy controls and 21 individuals with mild cognitive
      impairment or mild Alzheimer's disease underwent neuropsychological evaluation
      and restriction spectrum imaging (RSI). Microstructural change in the
      hippocampus, entorhinal cortex, and white matter tracts previously shown to be
      vulnerable to Alzheimer's disease, was compared between healthy controls and
      impaired participants. Partial correlations and stepwise linear regressions
      examined whether baseline RSI metrics predicted subsequent cognitive decline, or
      change in RSI metrics correlated with cognitive change. In medial temporal gray
      and white matter, restricted isotropic diffusion and crossing fibers were lower,
      and free water diffusion was higher, in impaired participants. Restricted
      isotropic diffusion in the hippocampus declined more rapidly for cognitively
      impaired participants. Baseline hippocampal restricted isotropic diffusion
      predicted cognitive decline, and change in hippocampal and entorhinal restricted
      isotropic diffusion correlated with cognitive decline. Within controls, changes
      in white matter restricted oriented diffusion and crossing fibers correlated with
      memory decline. In contrast, there were no correlations between rates of cortical
      atrophy and cognitive decline in the full sample or within controls. Changes in
      medial temporal lobe microarchitecture were associated with cognitive decline in
      prodromal Alzheimer's disease, and these changes were distinct from
      microstructural changes in normal cognitive aging. RSI metrics of brain
      microstructure may hold value for predicting cognitive decline in aging and for
      monitoring the course of Alzheimer's disease.

PMID- 30290304
TI  - miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic
      Cancer.
AB  - Extensive research has suggested that miR-7 plays a critical role in cancer
      progression. However, the biological function of miR-7 in pancreatic cancer (PC)
      progression is poorly understood. Therefore, in the present study, we
      investigated the function of miR-7 and its molecular mechanism in PC progression.
      We used multiple methods, such as MTT, FACS, Transwell assay, RT-PCR, western
      blotting, and transfection to investigate the role of miR-7 in PC cells. We found
      that miR-7 suppressed cell growth, migration, and invasion but induced apoptosis
      in PC cells. Moreover, overexpression of miR-7 repressed tumor growth in mice,
      suggesting that miR-7 could exert its tumor-suppressive function in PC.
      Mechanistically, we validated that MAP3K9 is a direct target of miR-7, which
      significantly enhanced PC cell proliferation and inhibited cell apoptosis partly
      through activation of the MEK/ERK pathway and NF-kappaB pathway. Moreover, rescue
      experiments also showed that miR-7 suppressed PC cell proliferation and induced
      PC cell apoptosis by directly targeting MAP3K9, leading to inhibition of the
      MEK/ERK and NF-kappaB pathways. Taken together, these results suggest that miR
      7/MAP3K9 is critically involved in PC progression and that miR-7 may be a
      potential target for PC treatment.

PMID- 30290305
TI  - Ablation of a Single N-Glycosylation Site in Human FSTL 1 Induces Cardiomyocyte
      Proliferation and Cardiac Regeneration.
AB  - Adult mammalian hearts have a very limited regeneration capacity, due largely to
      a lack of cardiomyocyte (CM) proliferation. It was recently reported that
      epicardial, but not myocardial, follistatin-like 1 (Fstl1) activates CM
      proliferation and cardiac regeneration after myocardial infarction (MI).
      Furthermore, bacterially synthesized human FSTL 1 (hFSTL1) was found to induce CM
      proliferation, whereas hFSTL1 synthesized in mammals did not, suggesting that
      post-translational modifications (e.g., glycosylation) of the hFSTL1 protein
      affect its regenerative activity. We used modified mRNA (modRNA) technology to
      investigate the possible role of specific hFSTL1 N-glycosylation sites in the
      induction, by hFSTL1, of CM proliferation and cardiac regeneration. We found that
      the mutation of a single site (N180Q) was sufficient and necessary to increase
      the proliferation of rat neonatal and mouse adult CMs in vitro and after MI in
      vivo, respectively. A single administration of the modRNA construct encoding the
      N180Q mutant significantly increased cardiac function, decreased scar size, and
      increased capillary density 28 days post-MI. Overall, our data suggest that the
      delivery of N180Q hFSTL1 modRNA to the myocardium can mimic the beneficial effect
      of epicardial hFSTL1, triggering marked CM proliferation and cardiac regeneration
      in a mouse MI model.

PMID- 30290306
TI  - Protecting Pax6 3' UTR from MicroRNA-7 Partially Restores PAX6 in Islets from an
      Aniridia Mouse Model.
AB  - Aniridia is a rare congenital syndrome that is associated with reduced visual
      acuity and progressive loss of vision. Aniridia patients may also develop
      systemic health issues associated with defects in the pancreas, digestive, and
      central nervous systems. The spectrum of symptoms associated with aniridia is due
      to haploinsufficiency of the paired box 6 gene (PAX6) and its role in the
      development and maintenance of the affected tissues. Here, we isolated pancreatic
      islets from mice heterozygous for Pax6 to test whether a Pax6-specific miRNA
      suppression (target protector) strategy can restore PAX6 protein levels. We show
      that miR-7 and miR-375 target specific sites within the Pax6 3' UTR in a mouse
      pancreatic beta-insulinoma cell line. Tough decoys (Tuds) against miR-7 and miR
      375 increase expression of a mouse Pax6 3' UTR luciferase reporter and increase
      PAX6 protein levels in these cells. Finally, we demonstrate that the shielding of
      the miR-7 binding site with a target protector restores PAX6 protein levels in
      the Pax6 heterozygous islets. The data presented here represent a proof of
      concept for RNA-based therapy for the progressive defects associated with
      aniridia and suggest the target protector approach may be a useful therapeutic
      strategy for other haploinsufficiency diseases.

PMID- 30290308
TI  - Effects of OASIS(r) phenolic foam on hydraulic behaviour of permeable pavement
      systems.
AB  - Sustainable drainage is a major challenge for highway and environmental agencies
      to mitigate flooding and understand the optimum design parameters of pavement
      structure. This paper experiments the hydraulic properties of OASIS(r) phenolic
      foam material examining infiltration rate and steady-state behaviour, water
      storage capacity of different thicknesses of OASIS(r) material, and the effect of
      OASIS(r) material in deferring the water peak flow during rainfall intensities of
      100 mm/h, 243 mm/h, 400 mm/h, and 563 mm/h. This paper designs an application
      programme that estimates the optimal thickness of OASIS(r) layer to retain 100%
      of stormwater for a duration of 15 min. The results from laboratory tests
      corroborate the performance efficiency of OASIS(r) material to delay peak
      stormwater flow and mitigate flooding. The OASIS(r) materials not only increase
      the ability of permeable pavement system to absorb and retain stormwater up to a
      saturation limit but also retain the nutrient contaminants infiltrate to
      groundwater. The designed application programme will help the designers and
      constructors to increases the drainage efficiency of pavement structure by
      estimating the optimal thickness of OASIS(r) layer required to delay peak
      stormwater flow during maximum rainfall intensities.

PMID- 30290307
TI  - miR-409 Inhibits Human Non-Small-Cell Lung Cancer Progression by Directly
      Targeting SPIN1.
AB  - Lung cancers, the leading cause of cancer mortality worldwide, are characterized
      by a high metastatic potential. Growing evidence reveals that Spindlin 1 (SPIN1)
      is involved in tumor progression and carcinogenesis. However, the role of SPIN1
      in non-small-cell lung cancer (NSCLC) and the molecular mechanisms underlying
      SPIN1 in human NSCLC remain undetermined. Here we examined the function of SPIN1
      in human NSCLC and found that the expression of SPIN1 was closely correlated with
      the overall survival and poor prognosis of NSCLC patients. Aberrant regulation of
      microRNAs (miRNAs) has an important role in cancer progression. We revealed that
      miR-409 inhibits the expression of SPIN1 by binding directly to the 3' UTR of
      SPIN1 using dual-luciferase reporter assays. Overexpression of miR-409
      significantly suppressed cell migration, growth, and proliferation by inhibiting
      SPIN1 in vitro and in vivo. SPIN1 overexpression in miR-409-transfected NSCLC
      cells effectively rescued the suppression of cell migration, growth, and
      proliferation regulated by miR-409. miR-409 regulates the PI3K/AKT (protein
      kinase B) pathway in NSCLC. Moreover, clinical data showed that NSCLC patients
      with high levels of miR-409 experienced significantly better survival. miR-409
      expression was also negatively associated with SPIN1 expression. Taken together,
      these findings highlight that the miR-409/SPIN1 axis is a useful pleiotropic
      regulatory network and could predict the metastatic potential in NSCLC patients
      early, indicating the possibility that miR-409 and SPIN1 might be attractive
      prognostic markers for treating NSCLC patients.

PMID- 30290309
TI  - Comprehensive evaluation and scenario simulation for the water resources carrying
      capacity in Xi'an city, China.
AB  - The quantity and quality of water resources are of great importance in
      maintaining urban socio-economic development. Accordingly, substantial research
      has been conducted on the concept of the water resources carrying capacity
      (WRCC). In this study, analytic hierarchy process (AHP) and system dynamics (SD)
      models were combined to construct a multi-criteria evaluation system of the WRCC
      and a socio-economic/water resources SD model for Xi'an. The developmental trends
      of the society, economy, water supply/demand, and wastewater discharge were
      obtained from 2015 to 2020 using five scenarios designed for distinct purposes;
      these scenarios and trends were comprehensively evaluated using a combination of
      qualitative and quantitative analyses. The results indicated that the WRCC (0.32
      in 2020) in Xi'an will shift from a normal to a poor state if the current social
      development pattern is maintained; therefore, we conclude that the socio-economic
      development of Xi'an is unsustainable. However, under a comprehensive scheme, the
      WRCC index (0.64 in 2020) will increase by 48% compared with the WRCC index under
      a business-as-usual scenario. Further, some practical suggestions, including the
      promotion of industrial reforms and the improvement of water-use efficiency and
      recycling policies, were provided for improving the regional WRCC.

PMID- 30290310
TI  - An energy-friendly alternative in the large-scale production of soybean oil.
AB  - Soybean oil is widely used as cooking oil, whereas the soybean cake is a valuable
      ingredient for animal food. The extraction of soybean oil is an energy-intensive
      process, with additional significant impact on the environment via the wastewater
      and hexane emissions. The research investigated different ways to minimize the
      energy consumption. In a traditional process, both direct (live) steam and
      indirect steam heating (jackets, tubular exchangers) are used to deliver the
      required heat duty. Direct steam injection is restricted to the first evaporator
      and the stripper, for a total of 620 kg/h. Indirect steam is also applied in the
      evaporators for a total of 6.44 MW. The desolventizing process requires a steam
      energy input of 8.15 MW. Integration of a heat exchanger network in the
      evaporation and stripping part of the process reduces the amount of direct steam
      usage from 620 kg/h to 270 kg/h and of the indirect heat duty from 6.44 to 5.05
      MW. In the cake desolventizing part of the process, the energy requirement is
      reduced from 8.15 to 2.12 MW. The overall gross energy saving is hence ~50%. The
      improvements moreover reduce both the waste water loadings by 56.5% and the CO2
      emissions by 62.5%. Hexane emissions are moreover significantly (>90%) reduced.

PMID- 30290311
TI  - The avian influenza virus PA segment mediates strain-specific antagonism of BST
      2/tetherin.
AB  - BST-2 is an antiviral protein described as a powerful cross-species transmission
      barrier for simian immunodeficiency viruses. Influenza viruses appear to interact
      with BST-2, raising the possibility that BST-2 may be a barrier for cross-species
      transmission. An MDCK-based cell line expressing human BST-2 was generated to
      study human-derived A/Puerto Rico/8/36 (H1N1; PR8) as well as two low pathogenic
      avian influenza viruses (subtypes H4N6 and H6N1). The H4N6 and H6N1 viruses were
      less affected by BST-2 expression than PR8, due to their ability to decrease BST
      2 levels, a function localized to the PA segment of both avian viruses.
      Experiments with PA-mutant and -chimeric viruses confirmed that the avian PA
      segment conferred BST-2 downregulation and antagonism. These results indicate a
      species-specific ability of PA from low pathogenic avian viruses to mitigate
      human BST-2 antiviral activity, suggesting that BST-2 is unlikely to be a general
      cross-species barrier to transmission of such viruses to humans.

PMID- 30290313
TI  - Netrin-1 prevents the attachment of monocytes to endothelial cells via an anti
      inflammatory effect.
AB  - Netrin-1 is best known for its function guiding axon growth and migration. Netrin
      1 has been shown to be involved in regulating cardiovascular function. In this
      study, we aimed to understand the biological role of Netrin-1 and its receptor
      Unc5b in endothelial cells. Our results demonstrate that Unc5b was moderately
      expressed in human aortic endothelial cells (HAECs) and TNF-alpha had a dose
      dependent inhibitory effect on Unc5b level. Netrin-1 potently suppressed TNF
      alpha-induced vascular adhesion molecules VCAM-1, ICAM-1, E-selectin and blocked
      the adhesion of monocytes to endothelial cells. Netrin-1 also suppressed TNF
      alpha-induced production of cytokines including MCP-1, IL-1beta, and IL-6.
      Importantly, Netrin-1 suppressed toll like receptor 4 (TLR4) expression and
      prevented NF-kappaB activation. Mechanistically, Netrin-1 reduced TNF-alpha
      induced IKK and IkappaBalpha activation and prevented degradation of
      IkappaBalpha. Netrin-1 reduced nuclear accumulation of p65 and strongly
      suppressed NF-kappaB promoter activation. Collectively, our data demonstrated
      that signaling of Netrin-1 and its receptor Unc5b had an anti-inflammatory effect
      in endothelial cells. Netrin-1 signaling could be imperative for normal
      endothelial function.

PMID- 30290314
TI  - TGF-beta1-Induced Airway Smooth Muscle Cell Proliferation Involves TRPM7
      Dependent Calcium Influx via TGFbetaR/SMAD3.
AB  - BACKGROUND: TRPM7 in mast cells plays a key role in asthma. However, the effect
      of TRPM7 on TGF-beta1-induced airway smooth muscle cell (ASMC) proliferation
      remains unclear. Therefore, we designed this study to explore whether TRPM7 is
      involved in TGF-beta1-induced ASMC proliferation. METHODS: An asthmatic mouse
      model was established, and the expressions of TGF-beta1 and TRPM7 in mice lungs
      were detected using enzyme-linked immunosorbent assay (ELISA) and western
      blotting. In addition, murine ASMCs were cultured and stimulated with TGF-beta1.
      Possible TGF-beta1 and TRPM7 interactions were examined using RT-PCR and western
      blotting analyses with ASMCs. The effect of TRPM7 knockdown on ASMC calcium
      influx was assessed by the fluorescent indicator indo-1. MTT and flow cytometry
      were applied to evaluate the effects of TRPM7 knockdown on ASMC proliferation and
      apoptosis. RESULTS: TGF-beta1 elevated the expression of TRPM7 via
      TGFbetaR/SMAD3. Knocking down TRPM7 decreased the intracellular Ca2+
      concentration and cellular proliferation of ASMCs, although apoptosis remained
      unaffected. CONCLUSIONS: Our initial findings suggest that TRPM7 inhibition may
      prevent asthma-induced airway remodeling.

PMID- 30290312
TI  - Versatile targeting system for lentiviral vectors involving biotinylated
      targeting molecules.
AB  - Conjugating certain types of lentiviral vectors with targeting ligands can
      redirect the vectors to specifically transduce desired cell types. However,
      extensive genetic and/or biochemical manipulations are required for conjugation,
      which hinders applications for targeting lentiviral vectors for broader research
      fields. We developed envelope proteins fused with biotin-binding molecules to
      conjugate the pseudotyped vectors with biotinylated targeting molecules by simply
      mixing them. The envelope proteins fused with the monomeric, but not tetrameric,
      biotin-binding molecules can pseudotype lentiviral vectors and be conjugated with
      biotinylated targeting ligands. The conjugation is stable enough to redirect
      lentiviral transduction in the presence of serum, indicating their potential in
      in vivo . When a signaling molecule is conjugated with the vector, the
      conjugation facilitates transduction and signaling in a receptor-specific manner.
      This simple method of ligand conjugation and ease of obtaining various types of
      biotinylated ligands will make targeted lentiviral transduction easily applicable
      to broad fields of research.

PMID- 30290315
TI  - Developing agent-based models of complex health behaviour.
AB  - Managing non-communicable diseases requires policy makers to adopt a whole
      systems perspective that adequately represents the complex causal architecture of
      human behaviour. Agent-based modelling is a computational method to understand
      the behaviour of complex systems by simulating the actions of entities within the
      system, including the way these individuals influence and are influenced by their
      physical and social environment. The potential benefits of this method have led
      to several calls for greater use in public health research. We discuss three
      challenges facing potential modellers: model specification, obtaining required
      data, and developing good practices. We also present steps to assist researchers
      to meet these challenges and implement their agent-based model.

PMID- 30290316
TI  - A senior high school-based survey on the long-term impact of the Wenchuan
      earthquake on survivors' quality of life: PTSD as a mediator.
AB  - Previous earthquake-related studies mostly focused on the prevalence and risk
      factors of post-traumatic stress disorder (PTSD), and there are only a few
      articles on the subsequent long-term outcomes of earthquakes. This study aimed to
      investigate the long-term impact of the Wenchuan earthquake on the quality of
      life (QOL) of surviving senior high school students 2-3 years post-disaster and
      to clarify whether PTSD was a mediator in the relationship of earthquake-related
      exposure and QOL. The study collected 1031 survivors' self-report questionnaires
      on socio-demographic data, earthquake-related experiences, PTSD symptoms (PCL-C),
      and QOL (WHOQOL-BREF). The results showed that earthquake-related exposure
      experiences were negatively associated with QOL scores, and the severity of PTSD
      symptoms was significantly and negatively related to QOL scores. Structural
      equation model (SEM) analysis showed that earthquake-related exposure was
      directly related to the severity of PTSD symptoms, while insignificantly directly
      related to QOL. Therefore, earthquake-related exposure was indirectly related to
      QOL (totally mediated by severity of PTSD symptoms). PTSD was a mediator in the
      relationship between earthquake-related exposure and QOL among adolescents:
      earthquake-related exposure affected the survivors' QOL mainly mediated by the
      PTSD symptoms that developed. Therefore, to improve the QOL of the survivors
      after an earthquake, more attention should be paid to survivors who have PTSD
      symptoms.

PMID- 30290317
TI  - Obsessive-compulsive symptom dimensions: Association with comorbidity profiles
      and cognitive-behavioral therapy outcome in pediatric obsessive-compulsive
      disorder.
AB  - Our aims were to examine: (1) classes of comorbid disorders in a sample of
      children and adolescents with Obsessive-Compulsive Disorder (OCD), (2) how these
      classes relate to obsessive-compulsive symptom dimensions, and (3) the extent to
      which obsessive-compulsive symptom dimensions predict Cognitive-Behavioral
      Therapy (CBT) outcome. Participants (N = 269) were assessed with the Kiddie
      Schedule for Affective Disorders and Schizophrenia (K-SADS-PL) and the Children's
      Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Latent Class Analysis (LCA) was
      used to identify comorbidity classes. Regression analyses were used to evaluate
      symptom dimensions as predictors of treatment outcome and their relation to
      comorbidity classes. Comorbidity was included in the treatment outcome analyses
      as it can affect outcome. Comorbidity was best categorized by a three-class model
      and each class was distinctively correlated with the OCD symptom dimensions.
      Higher scores on the symmetry/hoarding factor increased the chance of responding
      to CBT by an odds ratio of 1.56 (p = 0.020) when controlled for age, gender, and
      comorbidity class. The harm/sexual factor (p = 0.675) and contamination/cleaning
      factor (p = 0.122) did not predict CBT outcome. Three clinically relevant
      comorbidity subgroups in pediatric OCD were identified. Patients who exhibited
      higher levels of symmetry/hoarding dimension were more prone to respond to CBT.

PMID- 30290318
TI  - Effects of perceived stress and professional values on clinical performance in
      practice nursing students: A structural equation modeling approach.
AB  - BACKGROUND: Clinical performance is regarded as a basic and core content of
      nursing quality. Professional values of nursing students may play an important
      role in improving clinical performance. Few studies reveal the relationship
      between professional values, perceived stress and clinical performance. This
      research has found that professional values play a moderating role in the
      relationship between perceived stress and clinical performance. OBJECTIVE: To
      examine the negative association between perceived stress and clinical
      performance among practice nursing students, and to determine whether
      professional values plays a moderating role in the relationship between perceived
      stress and clinical performance among Chinese practice nursing students. DESIGN:
      A cross-sectional descriptive design has been used. METHODS: From May to June
      2017, a total of 435 Chinese practice nursing students from 4 hospitals filled
      out the questionnaires. The response rate was 94.57%. Three questionnaires
      including the Perceived Stress Scale (PSS), Nursing Professional Value Scale
      Revised (NPVS-R), and Clinical Performance Scale (CPS). Structural equation
      modeling was used to deal with the relationships among perceived stress,
      professional values, and clinical performance. RESULTS: Perceived stress was
      negatively associated with clinical performance (P < 0.01). Professional values
      significantly affected clinical performance (P < 0.01) and moderated the
      relationship between perceived stress and clinical performance (P < 0.01).
      CONCLUSIONS: Perceived stress is negatively related to clinical performance among
      Chinese practice nursing students, and professional values moderates the
      relationship between perceived stress and clinical performance, which can form
      scientific evidence to develop intervention strategies to improve clinical
      performance.

PMID- 30290319
TI  - The concept of caring amongst first year diagnostic radiography students:
      Original research.
AB  - Student radiographers start their work integrated learning from their first year
      of studying and they are in constant contact with patients. Based on this
      interaction, it is imperative for all diagnostic radiography students to be
      caring professionals. The purpose of this study was to gain an understanding of
      caring amongst diagnostic student radiographers by exploring and describing their
      experiences of caring in the clinical environment. A qualitative, exploratory,
      descriptive and contextual research design was utilized. Focus group interviews
      were conducted with first year diagnostic radiography students. Purposive
      sampling was used to ensure information rich data was obtained. In keeping with
      qualitative research, participants were interviewed until data saturation was
      reached. Appreciative inquiry was used as an interview technique to encourage
      storytelling and to engage in narrative - rich communication. The 4-D model of
      appreciative inquiry, namely; Discovery, Dream, Destiny and Design, formed the
      basis for the interview questions. Data was analysed and coded and themes were
      created based on the interpretation of the data. Three themes were identified as
      being; caring as an integral part of a career choice, unpreparedness for
      interpersonal interactions and barriers and enablers for the development of a
      caring identity. Participants expressed an idealistic vision of what caring means
      to them as a student radiographer. Participants felt unprepared for their daily
      interpersonal interactions with patients and other staff. Recommendations to
      radiography educators would be to engage in more role-playing exercises,
      reflective practices and peer discussions.

PMID- 30290320
TI  - Health anxiety and cyberchondria among Ege University health science students.
AB  - It is common among health science students to incorrectly believe that they have
      contracted certain diseases they have recently studied. This can also be seen in
      the form of health anxiety and investigating health-related information via the
      internet. Health anxiety, cyberchondria and affecting factors are determined
      among health science students. The study was conducted at the faculties of
      Medicine, Pharmacy, Dentistry and Nursing in 2016-2017 with the participation of
      874 students. The data were gathered using a questionnaire as well as health
      anxiety and cyberchondria severity scales. In the presence of a health problem,
      14.2% of students seek health information via the internet. 83.7% use mobile
      phone to access the internet, 1/4 of students conduct health scanning once a week
      or more. To 65.4%, internet information is correct at medium and above level. No
      statistically significant difference was found with respect to students' gender,
      high school, places they lived before, parents' education and scales' scores. The
      cyberchondria scores of students with health problems are higher in the whole
      scale and in "distress and mistrust of medical professional" subscales. As the
      frequency of scanning on the internet increases, the scores of cyberchondria also
      increase significantly. Medical students had significantly higher scores in
      "distress, excessiveness and reassurance" subscales. Male students' "mistrust of
      medical professional and compulsion" subscales scores were also higher. It was
      determined that the presence of the health problem was effective on the
      cyberchondria. Identification of somatoform problems like health anxiety and
      cyberchondria may help to regulate the education program.

PMID- 30290321
TI  - Nitritation, nitrous oxide emission pathways and in situ microbial community in a
      modified University of Cape Town process.
AB  - Achieving nitritation is a prerequisite to promote nutrients removal and save
      energy, but emission of nitrous oxide as a greenhouse gas cannot be ignored. This
      study established the nitritation in a continuous-flow MUCT process and
      investigated the mechanism of N2O generation. The nitrite accumulation ratio
      (NAR) reached 95% by controlling the low DO of 0.3-0.5 mg/L and short HRT of 8 h.
      The 15N-isotope tracer experiment indicated that the percentage of nitrifier
      denitrification (ND) pathway increased by 12.7% under the limited-aeration mode,
      improving the stable operating of nitritation. Meanwhile, the autotrophic anammox
      pathway increased with the contribution ratio of 14.7% to N2 emission under the
      nitritation mode. The 15N-DNA-SIP revealed that the Nitrosomonas executed the ND
      pathway and the Planctomycetes conducted the anammox process, respectively. The
      integration of autotrophic and heterotrophic process based on nitritation
      technique has potential to solve the carbon-limited issue for total nitrogen
      removal in mainstream WWTPs.

PMID- 30290322
TI  - Denitrification- and anammox-dominant simultaneous nitrification, anammox and
      denitrification (SNAD) process in subsurface flow constructed wetlands.
AB  - Simultaneous nitrification, anammox and denitrification (SNAD) process was
      developed in subsurface flow constructed wetlands (SFCWs) to treat polluted
      surface water. The effects of vegetation, hydraulic retention time (HRT), C/N,
      and influent nitrogen forms on nitrogen removal and microbial communities were
      investigated. Results showed that denitrification- and anammox-dominant SNAD
      corresponded to nitrate- and ammonia-dominant influent, respectively, and both
      could achieve more efficient nitrogen removal in planted SFCWs than the unplated.
      These higher efficiencies were due to the microbial growth, organic carbon
      release, oxygen supply and plant uptake promoted by vegetation. The electron
      donors accelerated denitrification but inhibited ammonia oxidation with deficient
      oxygen. Anammox contributed to nitrogen removal of 27.34% under oxygen-limited
      conditions without vegetation. Anammox combined with denitrification and plant
      uptake were over 90% in planted SFCWs. For the investigated factors, the ammonia,
      nitrate and C/N were the most significant ones influencing the microbial
      communities, further nitrogen removal pathways and performances.

PMID- 30290323
TI  - Bioconversion of plant biomass hydrolysate into bioplastic
      (polyhydroxyalkanoates) using Ralstonia eutropha 5119.
AB  - Pretreatment of lignocellulosic biomass results in the formation of byproducts
      (furfural, hydroxymethylfurfural [HMF], vanillin, acetate etc.), which affect
      microbial growth and productivity. Furfural (0.02%), HMF (0.04%), and acetate
      (0.6%) showed positive effects on Ralstonia eutropha 5119 growth and
      polyhydroxyalkanoate (PHA) production, while vanillin exhibited negative effects.
      Response optimization and interaction studies between the variables glucose,
      ammonium chloride, furfural, HMF, and acetate using the response surface
      methodology resulted in maximum PHA production (2.1 g/L) at optimal variable
      values of 15.3 g/L, 0.43 g/L, 0.04 g/L, 0.05 g/L, and 2.34 g/L, respectively.
      Different lignocellulosic biomass hydrolysates (LBHs), including barley biomass
      hydrolysate (BBH), Miscanthus biomass hydrolysate (MBH), and pine biomass
      hydrolysate (PBH), were evaluated as potential carbon sources for R. eutropha
      5119 and resulted in 1.8, 2.0, and 1.7 g/L PHA production, respectively. MBH
      proved the best carbon source, resulted in higher biomass (Yx/s, 0.31 g/g) and
      PHA (Yp/s, 0.14 g/g) yield.

PMID- 30290324
TI  - Is active hepatitis C associated with the size of HIV reservoir in successfully
      treated patients?

PMID- 30290325
TI  - New-onset interictal headache in Persons with epilepsy (PWE): A case-control
      study.
AB  - PURPOSE: In our personal experience, headache is a frequent complaint in Persons
      with epilepsy (PWE) receiving antiepileptic drugs (AEDs), carbamazepine (CBZ) in
      particular. There is hardly any systematic study on AEDs-associated headache. We
      assessed the association of new-onset interictal headache in PWE with CBZ
      compared with other AEDs and factors associated with it. METHODS: Two thousand
      PWE on AEDs were screened, and 165 persons having new-onset interictal headache
      were identified. Eight persons were excluded because of comorbid illnesses that
      could potentially contribute to a headache. Finally, 157 were recruited for the
      study. One hundred fifty-seven age- and sex-matched PWE on AEDs, without
      headache, were recruited as controls. Headache questionnaire based on the
      International Classification of Headache Disorders (ICHD-II) criteria was used.
      Demographic factors, seizure characteristics, type and dose of AEDs, findings on
      electroencephalogram (EEG), and magnetic resonance imaging (MRI)/computerized
      tomography (CT) were recorded. RESULTS: Among PWE with headache, the majority [88
      (56.1%)] were on CBZ compared with other AEDs but not significantly different
      from controls. In 71 (45%) persons, the headache had migrainous character. In
      both univariate and multivariate analyses, lower seizure frequency and fewer EEG
      abnormalities were found to be independent predictors of headache. CONCLUSIONS:
      New-onset interictal headache is a significant issue in PWE; nonmigrainous
      headache is more common than the migrainous type. Carbamazepine was not found to
      have any predilection for new-onset interictal headache compared with other AEDs.
      A lower frequency of seizures and EEG abnormalities in PWE with headache may
      suggest that seizures contribute less to the development of headache and may
      further support the hypothesis that AEDs may be significant contributing factors
      for the headache.

PMID- 30290326
TI  - Multivariable prediction model of drug resistance in adult patients with
      generalized epilepsy from Colombia: A case-control study.
AB  - INTRODUCTION: Patients with drug-resistant epilepsy (DRE) account for most of the
      burden of epilepsy, and they have poor prognosis in seizure control, higher
      morbidity, and mortality. OBJECTIVES: The objective of the study was to develop a
      prognostic model of drug resistance in adult patients with generalized epilepsy
      from Colombia. METHODS: In this case-control study of patients with generalized
      epilepsy, patients were separated into two groups: one group with DRE (cases)
      according to the new International League Against Epilepsy (ILAE) definition
      after a complete evaluation performed by an epileptologist and the other group
      without DRE (control). Variables were analyzed to identify statistical
      differences between groups and were then selected to construct a prognostic model
      from a logistic regression. RESULTS: One hundred thirty-three patients with
      generalized epilepsy were studied. Thirty-eight (28.5%) patients had DRE, and 95
      (71.5%) did not have DRE. History of status epilepticus, abnormal findings from
      neurological examination, aura, any degree of cognitive impairment, epileptic
      seizures at any moment of the day, and any comorbidity were risk factors. The
      presence of seizures only in the waking state and idiopathic etiology were
      protective factors. A prognostic model was constructed with previously reported
      risk factors for DRE and other variables available in the population of this
      study. In the multivariable analysis, the history of status epilepticus (odds
      ratio (OR): 5.6, confidence interval (CI): 1.1-20.0, p = 0.031), abnormal
      findings from neurological examination (OR: 5.7, CI: 2.3-13.9, p = 0.000), and
      aura (OR: 6.1, CI: 1.8-20.8, p = 0.003) were strongly associated with DRE.
      CONCLUSIONS: In adult patients with generalized epilepsy, aura, abnormal findings
      from neurological examination, and history of status epilepticus were predictive
      factors for DRE.

PMID- 30290327
TI  - Plant-lead interactions: Transport, toxicity, tolerance, and detoxification
      mechanisms.
AB  - Natural and human activities introduced an excess level of toxic lead (Pb) to the
      environment. Pb has no known biological significance and its interactions with
      plants lead to the production of reactive oxygen species (ROS). Pb and/or ROS
      have the potential to cause phytotoxicity by damaging the tissue ultrastructure,
      cellular components, and biomolecules. These damaging effects may possibly result
      in the inhibition of normal cellular functioning, physiological reactions, and
      overall plant performances. ROS play a dual role and act as a signaling molecule
      in plant defense system. This system encircles enzymatic and non-enzymatic
      antioxidative mechanisms. Catalase, superoxide dismutase, peroxidase, and enzymes
      from the ascorbate-glutathione cycle are the major enzymatic antioxidants, while
      non-enzymatic antioxidants include phenols, flavonoids, ascorbic acid, and
      glutathione. Pb removal from contaminated sites using plants depend on the
      plant's Pb accumulation capacity, Pb-induced phytotoxicity, and tolerance and
      detoxification mechanisms plants adopted to combat against this phytotoxicity.
      However, the consolidated information discussing Pb-plant interaction including
      Pb uptake and its translocation within tissues, Pb-mediated phytotoxic symptoms,
      antioxidative mechanisms, cellular, and protein metabolisms are rather limited.
      Thus, we aimed to present a consolidated information and critical discussions
      focusing on the recent studies related to the Pb-induced toxicity and oxidative
      stress situations in different plants. The important functions of different
      antioxidants in plants during Pb stress have been reviewed. Additionally,
      tolerance responses and detoxification mechanisms in the plant through the
      regulation of gene expression, and glutathione and protein metabolisms to compete
      against Pb-induced phytotoxicity are also briefly discussed herein.

PMID- 30290328
TI  - The role of minocycline in alleviating aluminum phosphide-induced cardiac
      hemodynamic and renal toxicity.
AB  - Poisoning with aluminum phosphide (AlP) has been attributed to the high rate of
      mortality among many Asian countries. It affects several organs, mainly heart and
      kidney. Numerous literature demonstrated the valuable effect of minocycline in
      mitigating pathological symptoms of heart and kidney disease. The aim of the
      present study was to evaluate the probable protective effect of minocycline on
      cardiac hemodynamic parameters abnormalities and renal toxicity induced by AlP
      poisoning in the rat model. AlP was administered by gavage at 12 mg/kg body
      weight followed by injection of minocycline for two interval times of 12 and 24
      h, at 40, 80, 120 mg/kg body weight. Electrocardiographic (ECG) parameters were
      monitored, 30 min after AlP gavage for 6 h using an electronic cardiovascular
      monitoring device. Kidney tissue and serum were collected for the study of
      histology, mitochondrial complexes I, II, IV, lactate dehydrogenase (LDH) and
      myeloperoxidase (MPO) activity, ADP/ATP ratio, mitochondrial cytochrome c
      release, apoptosis, lactate, BUN, and Cr levels. The results demonstrated that
      AlP induces ECG abnormalities, and failure of heart rate and blood pressure,
      which improved significantly by minocycline. Minocycline treatment significantly
      improved complexes I, IV, MPO and LDH activities, and also reduced the ADP/ATP
      ratio, lactate level, release of cytochrome c, and apoptosis in the kidney
      following AlP-poisoning. Also, the histological results showed an improvement of
      kidney injury in minocycline treated groups. In conclusion, the findings of this
      study showed that minocycline could improve cardiac hemodynamic abnormalities and
      kidney injury following AlP-poisoning, suggesting minocycline might be a possible
      candidate for the treatment of AlP-poisoning.

PMID- 30290329
TI  - A new precise positioning method for piezoelectric scanner of AFM.
AB  - Atomic Force Microscopy (AFM) plays a vital role in nanoscience and
      nanotechnology due to its nanoscale resolution. However, the realization of
      highly precise measurement for AFM is still a challenge. A main factor is the
      positioning accuracy of the piezoelectric scanner (PZT), affected significantly
      by the hysteresis of PZT. The paper reports a new dynamic polynomial fitting
      method modeling hysteresis to achieve the inverse model of the PZT. The inverse
      model is used as the feedforward input, combined with the fuzzy feedback
      controller proposed in our former paper, to correct the nonlinear errors induced
      by the hysteresis. The method is demonstrated to be effective in improving the
      positioning accuracy of the lateral PZT. Its accuracy can achieve 1 nm.

PMID- 30290330
TI  - Influence of phosphate on tungstate sorption on hematite: A macroscopic and
      spectroscopic evaluation of the mechanism.
AB  - The environmental fate of the tungstate (VI) oxyanion [ e.g. mono tungstate and
      several polytungstate, generally expressed by W (VI)] is largely controlled by
      sorption on soil minerals, especially on iron oxide minerals. Molecular scale
      evaluation of W (VI) retention on iron oxides in the presence of competing
      oxyanions is scarce in literature. Here we report surface interaction mechanisms
      of W (VI) on hematite in the presence of phosphate (P) using macroscopic and in
      situ attenuated total reflectance Fourier transform infrared (ATR-FTIR)
      spectroscopic experiments. Batch sorption experiments were conducted using 2 g L
      1 hematite and 100 MUM W (VI) and P, in single ion system and in binary mixtures
      as a function of pH (4-11). In situ ATR-FTIR spectroscopic evaluation of P and W
      (VI) sorption on hematite was also carried out. The results from macroscopic
      experiments indicated that W (VI) sorption on hematite was not affected by P when
      W (VI) was added first. The influence of P on W (VI) sorption was noticed when W
      (VI) & P were added simultaneously or P was added first. The in situ ATR-FTIR
      spectroscopic data corroborated these findings. In addition, the spectroscopic
      data revealed that in the presence of P, the surface complexation mode of W (VI)
      differed as noted from either the absence of WO antisymmetric infrared (IR) band
      or the WOW stretching band. This study provides useful information on molecular
      level understanding of W (VI) surface complexation on hematite in the presence of
      competing ions such as P.

PMID- 30290331
TI  - Flavin homeostasis in the mouse retina during aging and degeneration.
AB  - Involvement of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN)
      in cellular homeostasis has been well established for tissues other than the
      retina. Here, we present an optimized method to effectively extract and quantify
      FAD and FMN from a single neural retina and its corresponding retinal pigment
      epithelium (RPE). Optimizations led to detection efficiency of 0.1 pmol for FAD
      and FMN while 0.01 pmol for riboflavin. Interestingly, levels of FAD and FMN in
      the RPE were found to be 1.7- and 12.5-fold higher than their levels in the
      retina, respectively. Both FAD and FMN levels in the RPE and retina gradually
      decline with age and preceded the age-dependent drop in the functional competence
      of the retina as measured by electroretinography. Further, quantifications of
      retinal levels of FAD and FMN in different mouse models of retinal degeneration
      revealed differential metabolic requirements of these two factors in relation to
      the rate and degree of photoreceptor degeneration. We also found twofold
      reductions in retinal levels of FAD and FMN in two mouse models of diabetic
      retinopathy. Altogether, our results suggest that retinal levels of FAD and FMN
      can be used as potential markers to determine state of health of the retina in
      general and more specifically the photoreceptors.

PMID- 30290332
TI  - Dietary fatty acids augment tissue levels of n-acylethanolamines in n
      acylphosphatidylethanolamine phospholipase D (NAPE-PLD) knockout mice.
AB  - N-acylethanolamines (NAEs) are lipid signaling mediators, which can be
      synthesized from dietary fatty acids via n-acylphosphatidylethanolamine
      phospholipase D (NAPE-PLD) and in turn influence physiological outcomes; however,
      the roles of NAPE-PLD upon dietary fatty acid modulation are not fully
      understood. Presently, we examine if NAPE-PLD is necessary to increase NAEs in
      response to dietary fatty acid manipulation. Post-weaning male wild-type
      (C57Bl/6), NAPE-PLD (-/+) and NAPE-PLD (-/-) mice received isocaloric fat diets
      containing either beef tallow, corn oil, canola oil or fish oil (10% wt/wt from
      fat) for 9 weeks. Brain docosahexaenoic acid (DHA) levels were higher (P<.01) in
      NAPE-PLD (-/+) (10.01+/-0.31 MUmol/g) and NAPE-PLD (-/-) (10.89+/-0.61 MUmol/g)
      than wild-type (7.72+/-0.61 MUmol/g) consuming fish oil. In NAPE-PLD (-/-) mice,
      brain docosahexaenoylethanolamide (DHEA) levels were higher (P<.01) after fish
      oil feeding suggesting that NAPE-PLD was not necessary for DHEA synthesis. Liver
      and jejunum arachidonoylethanolamide, 1,2-arachidonoylglycerol and DHEA levels
      reflected their corresponding fatty acid precursors suggesting that alternate
      pathways are involved in NAE synthesis. NAPE-PLD (-/-) mice had lower
      oleoylethanolamide levels in the jejunum and a leaner phenotype compared to wild
      type mice. Overall, these results demonstrate that dietary fatty acid can augment
      tissue NAEs in the absence of NAPE-PLD.

PMID- 30290333
TI  - Possible interaction of ROS, antioxidants and ABA to survive osmotic stress upon
      acclimation in Vigna radiata L. Wilczek seedlings.
AB  - Acclimation is a process of adjustment to gradual environmental change that
      enables plants to survive further stress by triggering some tolerance mechanism
      possibly involving ABA, ROS and oxidative metabolism. Here we have studied
      acclimation responses in terms of the performances with regard to physiological
      (growth and relative water content) and biochemical (chlorophyll, carotenoids,
      protein, malondialdehyde, sugar content) attributes, ABA production and stomatal
      sensitivity to exogenous ABA, extracellular ROS production and activation of
      antioxidant system. Our study reveals that repeated exposure to short-term mild
      water stress simulated by polyethylene glycol (PEG-6000) induces acclimation in
      mung bean (Vigna radiata L. Wilczek) seedlings. Acclimation induced tolerance was
      associated with reduced leaf size and enhanced root growth, accumulation of
      soluble sugar as osmoprotectant, maintenance of water potential, lessening of
      membrane damage as indicated by lower MDA content. Acclimated mung bean seedlings
      have shown greater degree of tolerance through increased production of and
      enhanced sensitivity to ABA (as reflected by faster stomatal closure), enhanced
      production of extracellular O2.- and H2O2 and the elevated activities of
      antioxidative enzymes to control the oxidative burst. Taken together, the results
      convey that acclimated seedlings minimize osmotic stress-induced damage through a
      possible network of ABA, ROS and antioxidants.

PMID- 30290334
TI  - Soybean leaves transcriptomic data dissects the phenylpropanoid pathway genes as
      a defence response against Phakopsora pachyrhizi.
AB  - Asian soybean rust (ASR), caused by the obligate biotrophic fungus Phakopsora
      pachyrhizi, is responsible for severe yield losses of up to 90% in all soybean
      producing countries. Till today, eight resistance to Phakopsora pachyrhizi (Rpp)
      loci have been mapped in soybean. Their resistance mechanism is race specific but
      largely unknown. The transcriptomes of susceptible BRS184 and Rpp3 with ASR
      isolates T1-2 at 24 h after inoculation (hai) and without ASR inoculation (mock)
      were annotated by similarity searching with different databases. A total of 4518
      differentially expressed genes were identified. We found 70.89%, 56.61%, 32.13%,
      and 56.04% genes in the protein family databases (PFAM), Gene Ontology (GO),
      Eukaryotic clusters of Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes
      and Genomes Pathway (KEGG), respectively. KEGG disclosed that 52% of the
      phenylpropanoid pathway related genes were up-regulated. The relative gene
      expression study for selected genes of that pathway was conducted by RT-qPCR
      using Rpp1-Rpp4 carrying lines with T1-2 infection. The RT-qPCR results revealed
      that the Rpp lines utilized these genes in a rate limiting manner as a defence
      response. With the exception of glycinol 4-dimethylallyltransferase (G4DT) and
      chalcone reductase (CHR), all the genes showed the greatest expression at 12 hai,
      but the gene expressions which occur between 24 and 96 hai make these Rpp lines
      unique to their respective ASR isolates. Moreover, functional coordination of
      arogenate dehydratase 6 (ADT6) and 4-hydroxy-3-methylbut-2-enyl diphosphate
      synthase (ispG), chalcone synthase (CHS) and CHR, and G4DT and phytyltransferase
      3 (PT3) may have a great impact on soybean resistance against ASR.

PMID- 30290335
TI  - Effects of non-uniform root zone salinity on growth, ion regulation, and
      antioxidant defense system in two alfalfa cultivars.
AB  - A split-root system was established to investigate the effects of uniform (0/0,
      50/50, and 200/200 mM salt [NaCl]) and non-uniform (0/200 and 50/200 mM NaCl)
      salt stress on growth, ion regulation, and the antioxidant defense system of
      alfalfa (Medicago sativa) by comparing a salt-tolerant (Zhongmu No.1) and salt
      sensitive (Algonquin) cultivar. We found that non-uniform salinity was associated
      with greater plant growth rate and shoot dry weight, lower leaf Na+
      concentration, higher leaf potassium cation (K+) concentration, lower lipid
      peroxidation, and greater superoxide dismutase (EC 1.15.1.1), catalase (EC
      1.11.1.6), and peroxidase (EC 1.11.1.7) activities, compared to uniform salt
      stress in both alfalfa cultivars. Under non-uniform salinity, a significant
      increase in Na+ concentration and Na+ efflux and a decline in K+ efflux in the no
      saline or low-saline part of the roots alleviated salt damage. Our results also
      demonstrated that proline and antioxidant enzymes accumulated in both the no- or
      low-saline and high-saline roots, revealing that osmotic adjustment and
      antioxidant defense had systemic rather than localized effects in alfalfa plants,
      and there was a functional equilibrium within the root system under non-uniform
      salt stress. The salt-tolerant cultivar Zhongmu No.1 exhibited greater levels of
      growth compared to Algonquin under both uniform and non-uniform salt stress, with
      Na+ tolerance and efflux abilities more effective and greater antioxidant defense
      capacity evident for cultivar Zhongmu No.1.

PMID- 30290336
TI  - Climate change in Malaysia: Trends, contributors, impacts, mitigation and
      adaptations.
AB  - PURPOSE: This paper reviews the past and future trends of climate change in
      Malaysia, the major contributors of greenhouse gases and the impacts of climate
      change to Malaysia. It also reviews the mitigation and adaptations undertaken,
      and future strategies to manage the impacts of regional climate change.
      METHODOLOGY: The review encompasses historical climate data comprising mean daily
      temperature, precipitation, mean sea level and occurrences of extreme weather
      events. Future climate projections have also been reviewed in addition to
      scholarly papers and news articles related to impacts, contributors, mitigation
      and adaptations in relation to climate change. FINDINGS: The review shows that
      annual mean temperature, occurrences of extreme weather events and mean sea level
      are rising while rainfall shows variability. Future projections point to
      continuous rise of temperature and mean sea level till the end of the 21st
      century, highly variable rainfall and increased frequency of extreme weather
      events. Climate change impacts particularly on agriculture, forestry,
      biodiversity, water resources, coastal and marine resources, public health and
      energy. The energy and waste management sectors are the major contributors to
      climate change. Mitigation of and adaptations to climate change in Malaysia
      revolve around policy setting, enactment of laws, formulation and implementation
      of plans and programmes, as well as global and regional collaborations,
      particularly for energy, water resources, agriculture and biodiversity. There are
      apparent shortcomings in continuous improvement and monitoring of the programmes
      as well as enforcement of the relevant laws. ORIGINALITY/VALUE: This paper
      presents a comprehensive review of the major themes of climate change in Malaysia
      and recommends pertinent ways forward to fill the gaps of mitigation and
      adaptations already implemented.

PMID- 30290337
TI  - Size-dependent concentrations and bioaccessibility of organophosphate esters
      (OPEs) in indoor dust: A comparative study from a megacity and an e-waste
      recycling site.
AB  - Indoor dust ingestion is an important pathway in human exposure to environmental
      pollutants, and the bioaccessibility of pollutants can largely influence human
      exposure risk assessment. In the present study, the concentrations and
      compositions of organophosphate esters (OPEs) were investigated for different
      sizes (50 MUm to 2 mm) of indoor dust collected from a megacity, Guangzhou, and
      an e-waste recycling site. The concentrations of total OPEs were 5360 to 6830
      ng/g and 560 to 20,500 ng/g across all sizes of dust from Guangzhou and the e
      waste site, respectively. The levels and compositions of OPEs were consistent in
      different fractions of dust from Guangzhou. The highest concentrations of OPEs
      were found in the finest fraction of dust from the e-waste site. OPEs in
      Guangzhou dust showed decreasing bioaccessibility when the log KOW of FRs
      increased from 4 to 11. The bioaccessibility of most OPEs in dust from the e
      waste site was much lower than those in Guangzhou dust, indicating low
      bioaccessibility in the components of dust, such as e-waste debris, from the e
      waste site. The human exposure risks of OPEs in dust from Guangzhou were
      generally higher than those in dust from the e-waste site. Chitosan and
      montmorillonite could significantly decrease the bioaccessibility of all OPEs,
      except for tri-ethyl phosphate (TEP) and tris-(2-butoxyethyl) phosphate (TBOEP)
      in dust (p < 0.05), indicating chitosan and montmorillonite as promising food
      additives to enhance the elimination of OPEs.

PMID- 30290339
TI  - Impact of sediment dredging on sediment phosphorus flux in a restored riparian
      wetland.
AB  - Many riverine wetlands have been drained for the creation of agricultural land;
      however, global declines in freshwater biodiversity have begun to motivate
      wetland restoration projects around the world. Legacy phosphorus (P) increases
      the risk that wetland restoration may liberate excess P to the water column and
      connecting waterbodies, resulting in a trade-off of restored habitat for degraded
      water quality. To avoid this trade-off, we dredged a former agricultural parcel
      prior to hydrologic reconnection, and evaluated restoration success by comparing
      sediment P dynamics before and after dredging. First, results from P adsorption
      isotherm experiments suggested that after dredging, the sediment would act as a
      sink for dissolved P only when water column soluble reactive phosphorus (SRP)
      concentrations exceeded 40 MUg L-1. Additionally, the dredging depth (~1 m on
      average) exposed sediment with significantly reduced P sorption capacities.
      Second, P release rates were measured in sediment cores that were incubated under
      two water temperatures (ambient; +2  degrees C) and two oxygen levels (oxic;
      hypoxic). Average maximum total phosphorus (TP) release rates ranged from 40 to
      85 mg m-2 d-1 before dredging and from 0 to 7 mg m-2 d-1 after dredging,
      resulting in a 95-99% reduction in TP release rates after dredging. Similar
      reductions were measured also for SRP release rates. The significant reduction in
      sediment P release after dredging now creates a high potential for this restored
      wetland to reduce net P loads into downstream waters by facilitating the
      deposition and burial of particulate P. We conclude that sediment dredging can be
      a useful technique for balancing the goals of habitat restoration and water
      quality improvements in wetlands restored on former agricultural lands.

PMID- 30290338
TI  - Improvement of the electro-bioremediation process of a non-polar herbicide
      polluted soil by means of surfactant addition.
AB  - Oxyfluorfen is a non-polar herbicide that may cause severe soil pollution. The
      present work studies the possible improvement due to surfactant addition in the
      efficiency of electro-bioremediation of a clay soil polluted which such a non
      polar, low-mobility pollutant. Two-week-long batch electro-bioremediation
      experiments were performed in a bench-scale device. Oxyfluorfen-polluted soil (20
      mg kg-1) was inoculated with an acclimated microbial culture, and several
      experiments were performed using different surfactant concentrations in the
      electrode wells (0.0, 2.5, 5.0, 10.0 and 20.0 g L-1 of SDS, sodium dodecyl
      sulphate). Experiments were performed under 1.0 V cm-1 and electrode polarity
      reversal. It was observed that the electro-osmotic flow (EOF) increased with SDS
      concentration and that SDS was successfully distributed across the soil, probably
      improving the oxyfluorfen mobility. Additionally, microbiological activity was
      fully maintained during the experiments. Electro-bioremediation without SDS
      removed 14% of the oxyfluorfen, while under 2.5 g L-1 SDS, the efficiency
      increased to 22% because of an expected improvement in the contact between the
      different species in the soil. However, higher SDS concentrations (between 10.0
      and 20.0 g L-1) caused a decrease in the oxyfluorfen removal efficiency, as SDS
      is an easily biodegradable compound and was preferably used as substrate by the
      microbial culture instead of oxyfluorfen. Additionally, the use of high
      concentrations of SDS was clearly inefficient, as high amounts of the surfactant
      were lost through the EOF, and even low amounts of oxyfluorfen were removed to
      the electrode wells, which means that ex situ treatment of the polluted water
      would be needed.

PMID- 30290340
TI  - Formation of Zn-Al layered double hydroxides (LDH) during the interaction of ZnO
      nanoparticles (NPs) with gamma-Al2O3.
AB  - Zinc and aluminum layered double hydroxides (Zn-Al LDH) are a common group of
      major Zn species in various Zn-contaminated soil/sediment environments, yet their
      formation pathways and underlying mechanisms under varied conditions are not well
      understood. This study investigated the formation of Zn-Al LDHs through the
      direct interaction of two solid substrates, ZnO nanoparticles (NPs) and a
      representative Al oxide, gamma-Al2O3. Batch experiments and complementary
      microscopic and spectroscopic analyses were conducted to elucidate the reaction
      kinetics and mechanisms, as well as the morphologic and structural evolution of
      the products. Dissolved Zn and Al concentrations decreased significantly in a
      dual solid system compared to a single solid system. A bulk Zn-Al LDH phase was
      found to form under a wide pH range (6.5-9.5). Aside from Zn-Al LDH, gamma-Al2O3
      was the main remaining solid phase at pH 6.5, whereas ZnO NPs were the main
      residual solid phases at pH 9.5. Formation of amorphous Zn(OH)2 was also observed
      at both pH values, likely due to Zn2+ release at low pH and Al(OH)4- adsorption
      at high pH. It is proposed that the formation of Zn-Al LDH occurs via a
      dissolution-sorption-coprecipitation process, where the solubility of ZnO NPs or
      gamma-Al2O3 solid phases determines the reaction pathways and kinetics under
      varied pH conditions. The results from this work revealed the transformation
      mechanisms for ZnO NPs under conditions from weakly acidic to alkaline pH with
      highly available Al particles and shed light on the environmental fate of ZnO NPs
      in Zn or ZnO NP contaminated environments.

PMID- 30290341
TI  - Biochar's impact on dissolved organic matter (DOM) export from a cropland soil
      during natural rainfalls.
AB  - Although biochar amendment to soil has achieved widely recognized benefits such
      as plant growth improvement and carbon sequestration, what impact it would have
      on soil carbon cycling, especially on the behavior of the active dissolved
      organic matter (DOM), is still unclear. This study evaluated biochar's effects on
      soil properties and the characteristics of DOM exporting from a cropland Entisol.
      The soil is the major arable land resource in the upper reaches of the Yangtze
      River, China and noted for its low soil organic matter and prevalence of
      preferential flow. Surface runoff, soil pore water and leachate were collected
      from the field upon a series of natural rainfall. Concentration of dissolved
      organic carbon (DOC) of soil pore water was found to respond strongly toward the
      rainfalls. Biochar application led to relatively higher DOC levels within the
      soil (p > 0.05). Despite apparent increase of DOC and EEM intensities for the
      freshly-amended soil, PARAFAC analyses indicated no changes in DOM's fluorophore
      compositions after two years of ageing. The identified DOM components (C1 and C2)
      showed similar dynamics with the DOCs in responding to the rainfalls. On the
      other hand, total flux of DOM leaching from biochar-amended plots during three
      monitored storms was on average 59% higher than the control (p > 0.05), whereas
      DOM export via surface runoff was slightly diminished. Noticeably, biochar
      amendment had caused a significant increase of >1000 MUm macropores and thus the
      enhanced infiltration of soil water. Such changes led to increased flow
      discharge, which in turn resulted in elevated leaching of organic carbon during
      rainfalls. The results therefore implies that changes of soil structure and
      hydraulic properties that will take place after biochar application merits
      attention as they may play a continuous role in influencing the transport of DOM
      and possibly other solutes via runoff processes.

PMID- 30290342
TI  - Sediment quality assessment in the Guadalquivir River (SW, Spain) using caged
      Asian clams: A biomarker field approach.
AB  - This study assesses the sediment quality of the Guadalquivir River watercourse
      between the Alcala del Rio dam and the city of Seville. The main objective of
      this work is to address sediment quality in the area using an integrative
      approach that links sediment contamination and toxicity using the Asiatic clam
      (Corbicula fluminea) under field conditions. This is the first study conducted in
      the area that use of a battery of biomarkers from exposure (GST, GPx) to adverse
      biological effect (DNA and histopathological damage) to identify the
      contamination adverse effects in a river area affected by a cocktail of different
      anthropogenic activities (urban, industrial, agricultural, etc.). The sediment
      quality characterized in the area shows a significant biological stress related
      to metal(loid)s at station located in Alcala del Rio in the river upper part of
      the studied area, being this stress toxic when approaching the city of Seville.
      The sediments located nearby this city showed toxicity by means of positive
      values in the biomarkers of effects measured in the caged clams and related to
      contaminants with an industrial and urban discharge origins. These results have
      shown the useful and strength of the biomarker approach used in this study that
      combines biomarker responses from exposure to effects and allows identifying the
      contamination adverse effects by means of using caging individuals of the Asian
      clam. It has been proved in the different experiments how once the exposure
      biomarkers reach a maximum value of their system the detoxification ability of
      the organisms is collapsed and then the biomarkers of effect are measured
      significantly in the different tissues. The use of field surveys using tolerant
      specie such as the Asian clam is recommendable to determine sediment quality
      under an integrative point of view as here reported.

PMID- 30290343
TI  - Characteristics, sources, water quality and health risk assessment of trace
      elements in river water and well water in the Chinese Loess Plateau.
AB  - Water resources and water quality are restrictive factors in the Chinese Loess
      Plateau (CLP), a unique area with most severe soil erosion, fragile ecology and
      water shortage. River and well water samples were firstly analyzed, and multiple
      methods and indexes, including principal component analysis (PCA), correlation
      analysis (CA), sodium adsorption ratio (SAR), water quality index (WQI), hazard
      quotient (HQ), and hazard index (HI), were used to investigate characteristics,
      water quality and health risk assessment of trace elements in CLP. The average
      trace elements concentrations were higher than the world average with a slightly
      alkaline characteristic. PCA and CA showed that Al, Fe, Li, B, As, and F had
      natural origins from loess weathering and leaching; Cr, Pb, Cd, Cu, Ag, and Tl
      were mainly from anthropogenic input; Co, Ni, and Mn were dominated by both
      anthropogenic and natural sources. The poor river water quality was mainly
      related with high sodium (alkalinity) and salinity hazard. The poor well water
      quality samples with high WQI values, especially for As, Cr, and B, were
      distributed in the northwest and the Fenhe River sub-basin. The pollution level
      of trace elements in rivers in CLP was in medium level compared with other rivers
      worldwide. Arsenic pollution was the worst in well water and was the potential
      pollutant in river water especially for children. Arid climate together with
      anthropogenic input and special water characteristics (high Na, pH, and low Ca)
      aggravated As pollution. More work should be done to monitor the secular
      variation and remove As in the high As areas. The results of this study can
      provide the basic data for efficient water management and human health protection
      in CLP.

PMID- 30290344
TI  - Organ-specific differences in mercury speciation and accumulation across ringed
      seal (Phoca hispida) life stages.
AB  - Methylmercury (MeHg) is a central nervous system toxicant and exposures can
      adversely affect the health of marine mammals. Mercuric selenide (HgSe) in marine
      mammal tissues is hypothesized to result from a protective detoxification
      mechanism, but toxicokinetic processes contributing to its formation are poorly
      understood. Here, new data is reported on speciated Hg concentrations in multiple
      organs of n = 56 ringed seals (Phoca hispida) from Labrador, Canada, and compare
      concentrations to previously published data from Greenland seals. A higher
      proportion of Hg is found to accumulate in the kidney of young-of-the-year (YOY)
      ringed seals compared to adults. A toxicokinetic model for Hg species is
      developed and evaluated to better understand factors affecting variability in Hg
      concentrations among organs and across life stages. Prior work postulated that
      HgSe formation only occurs in the liver of mature seals, but model results
      suggest HgSe formation occurs across all life stages. Higher proportions of HgSe
      in mature seal livers compared to YOY seals likely results from the slow
      accumulation and elimination of HgSe (total body half-life = 500 days) compared
      to other Hg species. HgSe formation in the liver reduces modeled blood
      concentrations of MeHg by only 6%. Thus, HgSe formation may not substantially
      reduce MeHg transport across the blood-brain barrier of ringed seals, leaving
      them susceptible to the neurotoxic effects of MeHg exposure.

PMID- 30290345
TI  - What are the impacts of demographic structure on CO2 emissions? A regional
      analysis in China via heterogeneous panel estimates.
AB  - This study comprehensively investigated the impacts of demographic structure on
      CO2 emissions in China at the national level and the regional level for the first
      time. Panel cointegration modeling was employed to test the long-run
      relationships between CO2 emissions and six demographic structure variables,
      namely, dependency ratio, sex ratio, higher education ratio, industrial
      employment ratio, urbanization ratio, and average household size. The fully
      modified ordinary least squares method was then applied to estimate the long-run
      elasticity of CO2 emissions for the six demographic structure variables. The
      results suggested that long-run relationships between CO2 emissions and
      demographic structure existed at both the national level and the regional level.
      Dependency ratio was found to exert negative effects on CO2 emissions in China
      and its three sub-regions. Positive associations between sex ratio and CO2
      emissions were revealed to exist in China and West China, and CO2 emissions
      elasticity for sex ratio was relatively high in West China. Higher education
      ratio had a positive effect on CO2 emissions in East China. Industrial employment
      ratio was found to positively correlate with CO2 emissions in China, East China,
      and Central China. Urbanization ratio was demonstrated to increase CO2 emissions
      at the national level and the regional level, and CO2 emissions elasticity for
      urbanization ratio decreased from West China to Central China, and then to East
      China. Negative correlations between average household size and CO2 emissions
      were detected at both the national level and the regional level. Based on the
      findings of this study, several practical recommendations were proposed,
      including optimizing age structure, promoting gender equality, advocating low
      carbon lifestyles and low-carbon consumption patterns, promoting industrial
      upgrading and industrial structure optimization, building low-carbon cities and
      less carbon-intensive public infrastructure systems, and improving residential
      energy efficiency.

PMID- 30290346
TI  - Effects of water deficit stress on agronomic and physiological responses of rice
      and greenhouse gas emission from rice soil under elevated atmospheric CO2.
AB  - Rice is the foremost staple food in the world, safeguarding the global food and
      nutritional security. Rise in atmospheric carbon dioxide (CO2) and water deficits
      are threatening global rice productivity and sustainability. Under real field
      conditions these climatic factors often interact with each other resulting in
      impacts that are remarkably different compared to individual factor exposure.
      Rice soils exposed to drought and elevated CO2 (eCO2) alters the biomass,
      diversity and activity of soil microorganisms affecting greenhouse gas (GHG)
      emission dynamics. In this review we have discussed the impacts of eCO2 and water
      deficit on agronomic, biochemical and physiological responses of rice and GHGs
      emissions from rice soils. Drought usually results in oxidative stress due to
      stomatal closure, dry weight reduction, formation of reactive oxygen species,
      decrease in relative water content and increase in electrolyte leakage at almost
      all growth and developmental phases of rice. Elevated atmospheric CO2
      concentration reduces the negative effects of drought by improving plant water
      relations, reducing stomatal opening, decreasing transpiration, increasing canopy
      photosynthesis, shortening crop growth period and increasing the antioxidant
      metabolite activities in rice. Increased scientific understanding of the effects
      of drought and eCO2 on rice agronomy, physiology and GHG emission dynamics of
      rice soil is essential for devising adaptation options. Integration of novel
      agronomic practices viz., crop establishment methods and alternate cropping
      systems with improved water and nutrient management are important steps to help
      rice farmers cope with drought and eCO2. The review summarizes future research
      needs for ensuring sustained global food security under future warmer, drier and
      high CO2 conditions.

PMID- 30290347
TI  - NDVI-based vegetation dynamics and its response to climate changes at Amur
      Heilongjiang River Basin from 1982 to 2015.
AB  - Vegetation in Northern Hemisphere, being sensitive to climate change, plays an
      important role in the carbon cycles between land and the atmosphere. The response
      of vegetation to climate change was analyzed at pixel, biome and regional scale
      in Amur-Heilongjiang River Basin (AHRB) for growing season, spring, summer and
      autumn using Normalized Difference Vegetation Index and gridded climate data for
      the period 1982-2015. NDVI and climate variables trend detection methods and
      correlation analysis were applied. The potential impacts of human activities on
      growing season NDVI dynamics were investigated further using residual trend
      analysis. Results showed that at river basin scale, growing season vegetation
      experienced a discontinuous greening trend with two reversals, demonstrating that
      NDVI initially increased to mid-1990s, then declined to mid-2000s, and finally
      rebounded to 2015. This may be attributed to the shifting between drought and wet
      trends, indicating growing season NDVI was mainly regulated by precipitation.
      Temperature was the dominant factor on affecting spring vegetation growth while
      autumn NDVI showed negative correlation with precipitation due to the relation of
      precipitation with sunshine hours available for photosynthesis. The response of
      vegetation growth to climatic variations varied among vegetation types. Grassland
      NDVI exhibited positive correlation with precipitation in all time ranges. NDVI
      of needleleaved forest, broadleaved forest, mixed forest and woodland were
      positively correlated with temperature in all seasons, while showing significant
      negative correlation with autumn precipitation. Residual trend analysis revealed
      that human activities might lead to the vegetation degradation in China farming
      zone of AHRB. Fires also play an important role in regulating vegetation dynamics
      in the region. Results of our analysis can be used by national governments from
      three countries of AHRB in managing and negotiating vegetation resources of the
      region.

PMID- 30290348
TI  - Hepatorenal protective effects of taurine and N-acetylcysteine against fipronil
      induced injuries: The antioxidant status and apoptotic markers expression in
      rats.
AB  - Fipronil (FPN), a commonly used phenylpyrazole pesticide can induce oxidative
      tissue damage following hazard usage. Due to the extensive household and
      commercial usage of FPN, its toxic effects on mammals received considerable
      attention. Finding the proper antioxidant that can overcome FPN-induced damage is
      essential. Therefore, the present study aimed to assess the hepatorenal
      ameliorative outcomes of N-acetyl cysteine (NAC) and taurine (TAU) against
      hepatorenal damage induced by FPN in male Wistar rats. Compared to control rats,
      oral FPN (at a dose of 19.4 mg kg-1 BW for five successive days) significantly
      increased serum activities (p <= 0.05) of alkaline phosphatase, lactate
      dehydrogenase and transaminases, in addition to total cholesterol, urea and
      creatinine levels. Moreover, FPN provoked oxidative damage indicated by increased
      malondialdehyde and nitric oxide formation and decreased glutathione
      concentration and activities of enzymatic antioxidants (superoxide dismutase,
      glutathione peroxidase and catalase) in the hepatic and renal tissues.
      Furthermore, FPN administration induced overexpression of the proapoptotic (Bax),
      while it downregulated the expression of the anti-apoptotic (Bcl-2) protein.
      Interestingly, oral administration of TAU (50 mg Kg-1 BW) and NAC (50 mg Kg-1
      BW), alone or in combination, five days prior to and five days along with FPN
      administration, significantly ameliorated (p <= 0.05) and normalized the harmful
      effects of FPN on serum biomarkers of hepatorenal injury, lipid peroxidation and
      tissue antioxidants. In conclusion, TAU and NAC, alone or in combination,
      provided significant hepatorenal protection against oxidative stress and
      apoptosis induced by FPN.

PMID- 30290349
TI  - Deriving nutrient criteria to support 'good' ecological status in European lakes:
      An empirically based approach to linking ecology and management.
AB  - European water policy has identified eutrophication as a priority issue for water
      management. Substantial progress has been made in combating eutrophication but
      open issues remain, including setting reliable and meaningful nutrient criteria
      supporting 'good' ecological status of the Water Framework Directive. The paper
      introduces a novel methodological approach - a set of four different methods -
      that can be applied to different ecosystems and stressors to derive empirically
      based management targets. The methods include Ranged Major Axis (RMA) regression,
      multivariate Ordinary Least Squares (OLS) regression, logistic regression, and
      minimising the mismatch of classifications. We apply these approaches to
      establish nutrient (nitrogen and phosphorus) criteria for the major productive
      shallow lake types of Europe: high alkalinity shallow (LCB1; mean depth 3-15 m)
      and very shallow (LCB2; mean depth < 3 m) lakes. Univariate relationships between
      nutrients and macrophyte assessments explained 29-46% of the variation.
      Multivariate models with both total phosphorus (TP) and total nitrogen (TN) as
      predictors had higher R2 values (0.50 for LCB1 and 0.49 for LCB2) relative to the
      use of TN or TP singly. We estimated nutrient concentrations at the boundary
      where lake vegetation changes from 'good' to 'moderate' ecological status. LCB1
      lakes achieved 'good' macrophyte status at concentrations below 48-53 MUg/l TP
      and 1.1-1.2 mg/l TN, compared to LCB2 lakes below 58-78 MUg/l TP and 1.0-1.4 mg/l
      TN. Where strong regression relationships exist, regression approaches offer a
      reliable basis for deriving nutrient criteria and their uncertainty, while
      categorical approaches offer advantages for risk assessment and communication, or
      where analysis is constrained by discontinuous measures of status or short
      stressor gradients. We link ecological status of macrophyte communities to
      nutrient criteria in a user-friendly and transparent way. Such analyses underpin
      the practical actions and policy needed to achieve 'good' ecological status in
      the lakes of Europe.

PMID- 30290350
TI  - Ecotoxicity of the lipid-lowering drug bezafibrate on the bioenergetics and lipid
      metabolism of the diatom Phaeodactylum tricornutum.
AB  - Pharmaceutical residues impose a new and emerging threat to the marine
      environment and its biota. In most countries, ecotoxicity tests are not required
      for all pharmaceutical residues classes and, even when mandatory, these tests are
      not performed using marine primary producers such as diatoms. These microalgae
      are among the most abundant class of primary producers in the marine realm and
      key players in the marine trophic web. Blood-lipid-lowering agents such as
      bezafibrate and its derivatives are among the most prescribed drugs and most
      frequently found human pharmaceuticals in aquatic environments. The present study
      aims to investigate the bezafibrate ecotoxicity and its effects on primary
      productivity and lipid metabolism, at environmentally relevant concentrations,
      using the model diatom Phaeodactylum tricornutum. Under controlled conditions,
      diatom cultures were exposed to bezafibrate at 0, 3, 6, 30 and 60 MUg L-1,
      representing concentrations that can be found in the vicinity of discharges of
      wastewater treatment plants. High bezafibrate concentrations increased cell
      density and are suggested to promote a shift from autotrophic to mixotrophic
      metabolism, with diatoms using light energy generated redox potential to
      breakdown bezafibrate as carbon source. This was supported by an evident increase
      in cell density coupled with an impairment of the thylakoid electron transport
      and consequent photosynthetic activity reduction. In agreement, the
      concentrations of plastidial marker fatty acids showed negative correlations and
      Canonical Analysis of Principal coordinates of the relative abundances of fatty
      acid and photochemical data allowed the separation of controls and cells exposed
      to bezafibrate with high classification efficiency, namely for photochemical
      traits, suggesting their validity as suitable biomarkers of bezafibrate exposure.
      Further evaluations of the occurrence of a metabolic shift in diatoms due to
      exposure to bezafibrate is paramount, as ultimately it may reduce O2 generation
      and CO2 fixation in aquatic ecosystems with ensuing consequences for neighboring
      heterotrophic organisms.

PMID- 30290351
TI  - Differences of cell surface characteristics between the bacterium Pseudomonas
      veronii and fungus Ophiostoma stenoceras and their different adsorption
      properties to hydrophobic organic compounds.
AB  - The first step of microbial biodegradation is the adsorption of pollutants on the
      microorganisms' surface, which is determined by the microorganism type and
      pollutant hydrophobicity. One fungus Ophiostoma stenoceras LLC and one bacterium
      Pseudomonas veronii ZW were chosen for the investigation of cell surface
      hydrophobicity and adsorption abilities to various organic compounds. Results
      showed that the fungus could better capture and adsorb organic compounds in
      liquid and gas phases, and the adsorption was a physical monolayer adsorption
      process. Much smaller partition coefficient for gas-fungus suggested that direct
      gaseous adsorption was preferred. The XPS (X-ray photoelectron spectroscopy)
      characterization further confirmed that several functional groups changed after
      the adsorption of compounds. The time taken for complete degradation of hexane,
      tetrahydrofuran and chlorobenzene was shorter with the addition of O. stenoceras
      LLC. Such findings are useful in exploring the special cell surface of fungus in
      adsorption and bioenhancement for organic treatment of organic contaminants using
      bacteria.

PMID- 30290352
TI  - The value of information: Realising the economic benefits of mapping seagrass
      meadows in the British Virgin Islands.
AB  - Carbon capturing coastal and marine habitats around the world are decreasing in
      extent every year, habitats found in abundance in Small Island Developing States'
      territories. However, these habitats are under threat by increased levels of
      economic activities and extreme weather events. Consequently, as those ecosystems
      become scarce their value is expected to increase. In this paper the "value of
      information", the increase in knowledge that renders a system or a function more
      valuable, from marine habitat mapping is presented through the (monetary)
      valuation of one regulating service provided by the newly mapped habitats.
      Mapping a section of a channel with a multibeam echosounder revealed more
      seagrass resources than in previous studies. Using values for both the Social
      Cost of Carbon and Abatement Cost methods, from the literature we estimate the
      value of the carbon sequestration and storage service these seagrass meadows
      provide. The impacts of hurricanes in the newly mapped seagrasses were also
      investigated. Despite the costs of mapping, monitoring and of projected losses of
      ecosystem services provision due to hurricanes, net benefits over a time period
      of 50 years were considerably larger. The new information provided highlights
      carbon capturing habitats as more important, enabling the "value of information"
      to inform policymaking.

PMID- 30290353
TI  - Free phenolic compounds in waters of the Ross Sea.
AB  - The presence of free phenolic compounds (PC) in Antarctic sea water has been
      investigated to explain their source and particle size distribution in the
      atmospheric aerosols, as determined in our previous research. The sea water
      samples were filtered to distinguish the PC concentrations in the particulate and
      dissolved fractions. Two sample preparation procedures were developed to quantify
      nine PC in both fractions. The highest concentrations were found in the dissolved
      fraction of Ross Sea water, with vanillin, vanillic acid, acetovanillone and p
      coumaric acid being the most abundant PC. Dissolved PC were mainly found in the
      upper part of water column. This facilitated the sea water-air exchange by bubble
      busting processes. In the aerosol, they were mainly found in the fine fraction,
      where these compounds have a higher degree of oxidation than PC detected in
      seawater, suggesting that they were newly emitted and they have been not yet
      oxidized. These results supported our previous hypothesis that PC were locally
      emitted into the atmosphere from the Ross Sea. Three different possible sources
      of PC are hypothesized for Antarctic sea waters: 1) from the intrusion of
      Modified Circumpolar Deep Water that may transport oceanic lignin; 2) from
      phytoplankton biomass that may be a source of PC in Antarctic waters since
      diatoms produce exudates that contain vanillic acid, p-coumaric acid and syringic
      acid; 3) from the melting of glaciers and sea ice: glaciers contain lignin that
      can be degraded, while in the sea ice there are diatoms that may release PC.
      Statistical analysis and the low value of vanillic acid/vanillin ratio indicated
      that the most plausible source for PC in the dissolved fraction was the
      senescence of phytoplankton. As a contrast, particulate PC with higher vanillic
      acid/vanillin ratios were ascribed to degraded lignin or the sorption of
      diagenically oxidized material on particles.

PMID- 30290354
TI  - Stable isotope analyses revealed the influence of foraging habitat on mercury
      accumulation in tropical coastal marine fish.
AB  - Bioaccumulation of toxic metal elements including mercury (Hg) can be highly
      variable in marine fish species. Metal concentration is influenced by various
      species-specific physiological and ecological traits, including individual diet
      composition and foraging habitat. The impact of trophic ecology and habitat
      preference on Hg accumulation was analyzed through total Hg concentration and
      stable isotope ratios of carbon (delta13C) and nitrogen (delta15N) in the muscle
      of 132 fish belonging to 23 different species from the Senegalese coast (West
      Africa), where the marine ecosystem is submitted to nutrient inputs from various
      sources such as upwelling or rivers. Species-specific ecological traits were
      first investigated and results showed that vertical (i.e. water column
      distribution) and horizontal habitat (i.e. distance from the coast) led to
      differential Hg accumulation among species. Coastal and demersal fish were more
      contaminated than offshore and pelagic species. Individual characteristics
      therefore revealed an increase of Hg concentration in muscle that paralleled
      trophic level for some locations. Considering all individuals, the main carbon
      source was significantly correlated with Hg concentration, again revealing a
      higher accumulation for fish foraging in nearshore and benthic habitats. The
      large intraspecific variability observed in stable isotope signatures highlights
      the need to conduct ecotoxicological studies at the individual level to ensure a
      thorough understanding of mechanisms driving metal accumulation in marine fish.
      For individuals from a same species and site, Hg variation was mainly explained
      by fish length, in accordance with the bioaccumulation of Hg over time. Finally,
      Hg concentrations in fish muscle are discussed regarding their human health
      impact. No individual exceeded the current maximum acceptable limit for seafood
      consumption set by both the European Union and the Food and Agriculture
      Organization of the United Nations. However, overconsumption of some coastal
      demersal species analyzed here could be of concern regarding human exposure to
      mercury.

PMID- 30290355
TI  - Assessing microbial contamination and antibiotic resistant bacteria using zebra
      mussels (Dreissena polymorpha).
AB  - Aquatic pollution with faecal bacteria and subsequent consumption of contaminated
      water or food is a worldwide issue that causes severe health effects (e.g.
      meningitis, salmonellosis, dysentery). In addition, the excessive use of
      antibiotics in animal husbandry and human medicine has enhanced the selective
      pressure on pathogenic bacteria, further increasing human health risks and
      detrimental effects on natural microbial communities. This urges the need to
      monitor faecal contamination using a time-integrated approach, as grab water
      samples can miss pathogen peaks. We tested the ability of zebra mussels
      (Dreissena polymorpha) to take up and depurate faecal indicator bacteria such as
      Escherichia coli and intestinal enterococci. Furthermore, we quantified the
      frequency of antibiotic resistant bacteria in water and mussels both in
      controlled laboratory tests and under in situ conditions downstream of a sewage
      treatment plant (STP). Laboratory results show that bacterial indicators in
      mussels were 132 times higher than their concentration in water, and that mussels
      retained bacteria up to 2 days after pulse exposure. Field results show
      decreasing bacterial concentrations in both water and mussels downstream the STP,
      with maximum E. coli concentrations ranging 173-9 cfu mL-1 in water and 2970-330
      cfu g-1 in mussels. Similarly, enterococci ranged 59-4 cfu mL-1 and 1450-240 cfu
      g-1 in water and mussels, respectively. High proportions of antibiotic resistant
      E. coli were found in mussels (72%) and water (65%), and slightly lower
      proportion of resistant enterococci was found in mussels (47%) and in water
      (34%). Moreover, 33% of the bacteria isolated from mussels were resistant to
      multiple antibiotics, which emphasizes that resistance is a common feature in
      surface waters and highlights the need for safe water management. Our results
      show that zebra mussels provide an efficient, time-integrating tool for
      quantifying faecal indicators, including resistant and multidrug resistant
      bacteria.

PMID- 30290356
TI  - Linking bioavailability and toxicity changes of complex chemicals mixture to
      support decision making for remediation endpoint of contaminated soils.
AB  - A six-month laboratory scale study was carried out to investigate the effect of
      biochar and compost amendments on complex chemical mixtures of tar, heavy metals
      and metalloids in two genuine contaminated soils. An integrated approach, where
      organic and inorganic contaminants bioavailability and distribution changes,
      along with a range of microbiological indicators and ecotoxicological bioassays,
      was used to provide multiple lines of evidence to support the risk
      characterisation and assess the remediation end-point. Both compost and biochar
      amendment (p = 0.005) as well as incubation time (p = 0.001) significantly
      affected the total and bioavailable concentrations of the total petroleum
      hydrocarbons (TPH) in the two soils. Specifically, TPH concentration decreased by
      46% and 30% in Soil 1 and Soil 2 amended with compost. These decreases were
      accompanied by a reduction of 78% (Soil 1) and 6% (Soil 2) of the bioavailable
      hydrocarbons and the most significant decrease was observed for the medium to
      long chain aliphatic compounds (EC16-35) and medium molecular weight aromatic
      compounds (EC16-21). Compost amendment enhanced the degradation of both the
      aliphatic and aromatic fractions in the two soils, while biochar contributed to
      lock the hydrocarbons in the contaminated soils. Neither compost nor biochar
      affected the distribution and behaviour of the heavy metals (HM) and metalloids
      in the different soil phases, suggesting that the co-presence of heavy metals and
      metalloids posed a low risk. Strong negative correlations were observed between
      the bioavailable hydrocarbon fractions and the ecotoxicological assays suggesting
      that when bioavailable concentrations decreased, the toxicity also decreased.
      This study showed that adopting a combined diagnostic approach can significantly
      help to identify optimal remediation strategies and contribute to change the over
      conservative nature of the current risk assessments thus reducing the costs
      associated with remediation endpoint.

PMID- 30290357
TI  - Summer is in winter: Disturbance-driven shifts in macroinvertebrate communities
      following hydroelectric power exploitation.
AB  - In Alpine streams, humans have strongly modified the interactions between
      hydraulic processes, geomorphology and aquatic life through dams, flow
      abstraction at water intakes and river channel engineering. To mitigate these
      impacts, research has addressed both minimum flows and flow variability to
      sustain aquatic ecosystems. Whilst such environmental flows might work downstream
      of dams, this may not be the case for water intakes. Intakes, generally much
      smaller than dams, are designed to abstract water and to leave sediment behind.
      Sediment accumulation then results in the need to flush intakes periodically,
      often more frequently than daily in some highly glaciated basins. Sediment
      delivery downstream is then maintained through short duration floods with very
      high sediment loads. Here we tested the hypothesis that sediment flushing, and
      the associated high frequency of bed disturbance, controls in-stream habitat and
      macroinvertebrate assemblages. We collected macroinvertebrates over a 17-month
      period from an Alpine stream as well as a set of lateral unperturbed tributaries
      that served as controls. In contrast to established conceptual models, our
      results showed that the stream is largely void of life during summer, but that
      populations recover rapidly as the frequency of intake flushing falls in early
      autumn, producing richer and larger populations in winter and early spring. The
      recovery in autumn may be due to the recruitment of individuals from tributaries.
      We conclude that intake flushing in summer inverts expected summer-winter
      macroinvertebrate abundances, and questions the extent to which environmental
      flows in intake-impacted Alpine streams will lead to improvements in instream
      macrofauna unless sediment also is managed.

PMID- 30290358
TI  - LC-HRMS suspect screening to show spatial patterns of New Psychoactive Substances
      use in Australia.
AB  - New Psychoactive Substances (NPS) are an ever-changing class of compounds
      designed to imitate the effects of current recreational drugs. Such a diverse
      market is difficult to assess by traditional means, while collected information
      can become obsolete before it is available. Wastewater-based epidemiology is one
      technique which can capture information on where and when NPS appear at the
      community level. The aim of this study was to identify NPS in wastewater samples
      using a suspect screening approach. Weekend samples were collected from 50
      wastewater treatment plants from Australian capital cities and regional areas
      across all eight States and Territories and screened against a database
      containing almost 200 NPS. A total of 22 different NPS were found across all
      regional and metropolitan wastewater treatment plants. Results showed that the
      most detected compounds were of the cathinone class, with both Alpha-PVP and
      methcathinone found in every region. In addition, five different synthetic
      cannabinoids were detected, at least once in half of the regions analysed.
      Herein, we report the first comprehensive nationwide analysis of NPS and show the
      utility of liquid chromatography-high resolution mass spectrometry screening for
      delivering spatial information of the NPS being consumed in communities.

PMID- 30290359
TI  - Using survival analysis to predict septic shock onset in ICU patients.
AB  - PURPOSE: To determine the efficacy of survival analysis for predicting septic
      shock onset in ICU patients. MATERIALS AND METHODS: We performed a retrospective
      analysis on ICU cases from Mercy Hospital St. Louis from 2012 to 2016. As part of
      the procedure for inclusion in the Apache Outcomes database, each case is
      reviewed by critical care clinicians to identify septic shock patients as well as
      the time of septic shock onset. We used survival analysis to predict septic shock
      onset in these cases and employed lagging to compensate for uncertainties in
      septic shock onset time. RESULTS: Survival analysis was highly effective at
      predicting septic shock onset, producing AUC values of >0.87. The methodology was
      robust to lag times as well as the specific method of survival analysis used.
      CONCLUSIONS: This methodology has the potential to be implemented in the ICU for
      real time prediction and can be used as a building block to expand the approach
      to other hospital wards or care environments.

PMID- 30290360
TI  - Microcystin-LR exposure induced nephrotoxicity by triggering apoptosis in female
      zebrafish.
AB  - Recently, several studies showed that microcystin-LR (MCLR) can accumulate and
      induce toxicity in kidney. However, the exact mechanism is unknown. The aim of
      this study was to explore the mechanism of MCLR-induced nephrotoxicity. To this
      end, adult zebrafish were exposed to MCLR (0, 1, 5 and 25 MUg/L) for 60 days.
      Exposure to MCLR caused histopathological lesions, which were characterized by
      renal tubules filled with eosinophilic casts, abnormal renal tubules,
      intertubular space decrease, and blood infiltration in renal cells. RNA-Seq
      analysis indicated that exposure to MCLR significantly interfered with renal gene
      expressions, and these genes were enriched in various pathways, such as oxidative
      phosphorylation, cell cycle, and protein processing in endoplasmic reticulum,
      which were related to apoptosis. Furthermore, terminal deoxynucleotide
      transferase-mediated deoxy-UTP nick end labelling (TUNEL) assay showed that MCLR
      exposure induced renal cell apoptosis. In addition, negative changes of the
      reactive oxygen species (ROS) level as well as apoptotic-related gene, protein
      expressions and enzyme activities suggested that MCLR could induce production of
      ROS, subsequently triggering apoptosis via p53-bcl-2 and caspase-dependent
      pathway in the kidney of zebrafish. Therefore, it can be concluded that apoptosis
      is a primary case of MCLR-induced nephrotoxicity.

PMID- 30290361
TI  - Impact of water and fertilizer management on arsenic bioaccumulation and
      speciation in rice plants grown under greenhouse conditions.
AB  - Arsenic (As), a non-threshold class I carcinogen, is a main source of human
      exposure to inorganic As for billions of people worldwide. Rice is much more
      effectual in accruing As into its grain and other parts. Therefore, strategies to
      reduce As accumulation in rice should be adopted. The impact of water [Alternate
      Wetting and Drying (AWD), incessant flooding (CF)] and fertilizer management
      [Silicon (Si@ control, 10 and 20 mg/kg soil) and Phosphorus (P@ control, 12.5 and
      25.0 mg/kg soil)] on the bioaccumulation of As in rice plants under different As
      graded paddy soils (control, 10, 20 mg/kg) using an Australian rice variety (cv.
      Sherpa) was investigated under greenhouse conditions. Results indicated that,
      arsenite accounted for >80% of the total inorganic As in pore water and total As
      concentration declined from 933 MUg/L to 177 MUg/L with time. AWD irrigation
      practice with Si fertilization significantly reduced the total As levels in pore
      water. Arsenic concentration in different rice plant tissues showed significant
      variations due to water and fertilizer management. Lower concentrations of As in
      rice grains were observed using AWD (average 93.0 MUg/kg) than those observed in
      CF (average 121 MUg/kg) irrigation practice. The addition of Si also
      significantly (p < 0.03) decreased As uptake by rice plants while adding of P has
      no significant effect and this is also true for Si and P interaction. AWD
      irrigation practice with Si fertilization resulted in a reduction of grain As
      level at around 12%-21%, while grain yield increased by 13%.

PMID- 30290362
TI  - Genotoxic effects of neurotoxin beta-N-methylamino-l-alanine in human peripheral
      blood cells.
AB  - The non-proteinogenic amino acid beta-N-methylamino-l-alanine (BMAA) is
      associated with the development of neurodegenerative diseases such as Alzheimer's
      disease, amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS-PDC)
      and amyotrophic lateral sclerosis. BMAA is known to induce neurotoxic effects
      leading to neurodegeneration via multiple mechanisms including misfolded protein
      accumulation, glutamate induced excitotoxicity, calcium dyshomeostasis,
      endoplasmic reticulum stress and oxidative stress. In the present study, for the
      first time, genotoxic activity of BMAA (2.5, 5, 10 and 20 MUg/mL) was studied in
      human peripheral blood cells (HPBCs) using the comet and cytokinesis-block
      micronucleus cytome assays. In addition, the influence of BMAA on the oxidative
      stress was assessed. At non-cytotoxic concentrations BMAA did not induce
      formation of DNA strand breaks in HPBCs after 4 and 24 h exposure; however, it
      significantly increased the number of micronuclei after 24 and 48 h at 20 MUg/mL
      and nucleoplasmic bridges after 48 h at 20 MUg/mL. The frequency of nuclear buds
      was slightly though non-significantly increased after 48 h. Altogether, this
      indicates that in HPBCs BMAA is clastogenic and induces complex genomic
      alterations including structural chromosomal rearrangements and gene
      amplification. No influence on oxidative stress markers was noticed. These
      findings provide new evidence that environmental neurotoxin BMAA, in addition to
      targeting common pathways involved in neurodegeneration, can also induce genomic
      instability in non-target HPBCs suggesting that it might be involved in cancer
      development. Therefore, these data are important in advancing our current
      knowledge and opening new questions in the understanding of the mechanisms of
      BMAA toxicity, particularly in the context of genotoxicity.

PMID- 30290364
TI  - Program opportunities of residential immersive life skills programs for youth
      with disabilities.
AB  - PURPOSE: Residential immersive life skills programs provide youth with the skills
      and outlooks needed to adopt new roles in life. Observed program opportunities
      and service providers' perceptions of opportunities were examined to determine
      program fidelity. Service providers' views of how the programs work were also
      examined. METHOD: 107 activity settings were observed across two summers at three
      programs, with opportunities assessed using the Measure of Environmental
      Qualities of Activity Settings (MEQAS-48). Activity settings were classified by
      session format (instructional versus experiential) and activity type (active
      physical, skill-based, self-improvement). Qualitative interviews were held with
      seven service providers. RESULTS: Service providers indicated the importance of
      life-preparatory learning opportunities for social interaction, choice, and skill
      development, which aligned with high observed MEQAS-48 opportunities for social
      interaction, choice in experiential session formats, and personal growth.
      Providers individualized program delivery to provide youth with personally
      meaningful and challenging experiences. Providers also discussed emergent,
      transformational outcomes, including enhanced awareness of strengths, enhanced
      confidence in skills, identity development, and greater awareness of future life
      possibilities. CONCLUSIONS: The study provided evidence of program fidelity,
      along with robust evidence for program opportunities as an active ingredient that
      may be transferable to the design and delivery of other transition-support
      programs.

PMID- 30290363
TI  - Creating and sustaining cooperative relationships between supervised injection
      services and police: A qualitative interview study of international stakeholders.
AB  - BACKGROUND: Supervised injection services (SIS) operate with special exemptions
      from drug law enforcement. Given the expansion of SIS and the opioid overdose
      crisis in numerous jurisdictions, now is a critical time to examine factors that
      contribute to cooperative SIS-police relationships. We sought to learn about SIS
      police relationships from international jurisdictions with well-established as
      well as newer SIS. METHODS: We conducted 16 semi-structured telephone interviews
      with SIS managers (n = 10) and police liaisons (n = 6) from 10 cities in seven
      different countries (Australia, Canada, Denmark, France, Germany, Netherlands,
      and Spain). All participants provided informed consent. We focused our coding and
      analysis on themes that emerged from the data. RESULTS: Five key contributors to
      cooperative SIS-police relationships emerged from the data: early engagement and
      dialogues; supportive police chiefs; dedicated police liaisons; negotiated
      boundary agreements; and regular face-to-face contact. Most participants
      perceived the less formalised, on-the-ground approach to relationship-building
      between police and SIS adopted in their city to be working well in general. SIS
      managers and police participants reported a lack of formal police training on
      harm reduction, and some thought that training was unnecessary given the
      relatively positive local SIS-police relationships they reported. CONCLUSION: Our
      qualitative study provides new, in-depth empirical examples of how police in
      varied international jurisdictions can come to accept and work cooperatively
      with, not against, SIS staff and clients. Investing ongoing effort in SIS-police
      relationships, in a manner that best suits local needs, may hold greater and more
      sustainable public health value than delivering specific curricula to police.

PMID- 30290365
TI  - Toxin diversity revealed by the venom gland transcriptome of Pardosa
      pseudoannulata, a natural enemy of several insect pests.
AB  - The pond wolf spider, Pardosa pseudoannulata, is one of the most dominant
      predators of several agriculture insect pests including mainly the rice
      planthoppers and leafhoppers in paddy fields in Asia. Venom has been an
      attractive subject as the powerful weapon of spiders due to the complex
      components secreted from venom gland. The transcriptome of P. pseudoannulata
      venom gland was sequenced in order to understand the diversity of venom
      components at the molecular level and provide a new perspective for insect pest
      management. A total of 48 potential peptide toxins were identified from 75,980
      assembled transcripts. Among them, 32 putative neurotoxin precursors were
      classified into six families systematically. In addition to neurotoxins, peptide
      toxins with potential antiviral and antifungal activities were annotated as well
      as the protease inhibitors. The diversity of P. pseudoannulata venom was firmly
      demonstrated with the presence of astacin-like metalloprotease toxins, Kunitz
      type serine protease inhibitors, venom allergen 5, hyaluronidase and other
      important venom components. In addition, the tissue expression profiles of the
      toxin-related genes were investigated in venom gland, brain, and fat body. The
      present study classified the diverse venom components P. pseudoannulata and
      provided essential information of potential insecticidal toxins for the
      biological control of insect pests.

PMID- 30290366
TI  - Genome-wide identification of the entire 90 glutathione S-transferase (GST)
      subfamily genes in four rotifer Brachionus species and transcriptional modulation
      in response to endocrine disrupting chemicals.
AB  - Genome-wide identification of glutathione S-transferase (GST), a major phase II
      detoxification enzyme, was investigated in four different aquatic model rotifer
      species Brachionus koreanus, B. plicatilis, B. rotundiformis, and B.
      calyciflorus. GSTs are ubiquitous antioxidant enzymes that play versatile
      function including cellular detoxification, stress alleviation, and production of
      the radical conjugates. Among the four rotifers, B. rotundiformis was found with
      the least number of GST genes (total 19 GST genes), whereas the other three
      species shared 23 to 24 GST genes. Among the identified GST genes, belonging to
      the cytosolic GST superfamily, the expansion of GST sigma classes mainly occurs
      through tandem duplication, resulting in tandem-arrayed gene clusters on the
      chromosomes. Overall, the number of genes discovered in this study was highest in
      the sigma class, zeta, alpha, and omega in descending order. With integration of
      phylogenetic analysis and xenobiotic-mediated GST mRNA expression patterns along
      with previous enzymatic activities, the functional divergence among species
      specific GST genes was clearly observed. This study covers full identification of
      GST classes in three marine rotifer and one fresh-water rotifer species and their
      important role in marine environmental ecotoxicology.

PMID- 30290367
TI  - The influence of crouch gait on sagittal trunk position and lower lumbar spinal
      loading in children with cerebral palsy.
AB  - BACKGROUND: Crouch gait is a common pattern in children with CP. Little
      investigation has been performed as to the role of the trunk during crouch gait.
      A compensatory movement of the trunk may alter the position of the ground
      reaction force with the effect of reducing the moment arm about the knee or hip.
      While this may benefit these joints in the context of reduced loading, there may
      be implications further up the kinematic chain at the level of the lumbar spine.
      RESEARCH QUESTION: Are compensatory movements of the trunk present during crouch
      gait in children with CP and are levels of loading at the lower lumbar spine
      affected? METHODS: A full barefoot lower limb and trunk 3-dimensional kinematic
      and kinetic analysis, with kinetics estimated at the spinal position of L5/S1,
      was performed on 3 groups of children, namely CP Crouch, CP No-Crouch and TD.
      Differences in trunk position and L5/S1 loading were compared between groups.
      RESULTS: Mean trunk position in relation to the pelvis and laboratory was not
      statistically significant between groups. At the level of the spine, no
      differences were present in mean position between groups for L5/S1 sagittal
      moment or anterior/posterior force. SIGNIFICANCE: Crouch gait does not elicit a
      compensatory response of the trunk in children with CP and, consequently,
      reactive forces and moments at the lower lumbar spine remain within normal
      limits. With this in mind, it is unlikely that a crouch gait pattern will affect
      the health of the spine over time in these children.

PMID- 30290368
TI  - Isoliquiritigenin protects against blood-brain barrier damage and inhibits the
      secretion of pro-inflammatory cytokines in mice after traumatic brain injury.
AB  - Traumatic brain injury (TBI) caused by an external mechanical force acting on the
      brain is a serious neurological condition. Inflammation plays an important role
      in prolonging secondary tissue injury after TBI, leading to neuronal cell death
      and dysfunction. Isoliquiritigenin (ILG) is a flavonoid monomer with anti
      inflammatory characteristic. Thus, we had investigated the potential protective
      effects of ILG on TBI-induced injuries and identified the mechanisms underlying
      it. Here, we have demonstrated that ILG preserves blood brain barrier (BBB)
      integrity in vivo, suppresses the activation of microglia and inflammatory
      responses in mice after TBI, consequently leading to neurofunctional deficits,
      brain oedema, structural damage, and macrophage infiltration. In vitro, ILG
      exerts anti-inflammatory effect, and upregulates tight junction proteins 120-beta
      catenin and occludin in SH-SY5Y cells under oxygen glucose
      deprivation/reoxygenation (OGD/D) condition. Additionally, we found that
      PI3K/AKT/GSK-3beta signalling pathway is involved in ILG treatment for TBI. To
      further confirm it, we had used SC79 (ethyl 2-amino-6-chloro-4-(1-cyano-2-ethoxy
      2-oxoethyl)-4H-chromene-3-carboxylate), an Akt specific activator, to activate
      Akt, we found that SC79 partially reduces the protective effect of ILG for TBI.
      Overall, our current study reveals the neuroprotective role of ILG on TBI-induced
      BBB damage, downregulated tight junction proteins via PI3K/AKT/GSK-3beta
      signalling pathway. Furthermore, ILG suppresses the secretion of pro-inflammatory
      cytokines after TBI through inhibiting the PI3K/AKT/GSK-3beta/NF-kappaB
      signalling pathway. Our findings suggest that GSK-3beta is a key regulatory
      factor during TBI-induced secretion of inflammatory cytokines, neuronal apoptosis
      and destruction of BBB.

PMID- 30290369
TI  - Rules to activate CD8+T cells through regulating subunits of opioid receptors by
      methionine enkephalin (MENK).
AB  - The goal of this work was to investigate how MENK could regulate the functions of
      CD8+T cells and to explore the relationship between this regulation and opioid
      receptor expression. Our results showed that the opioid receptors presented on
      the cell menbrane of CD8+T cells were MOR and DOR. MENK promoted the expression
      of opioid receptors as well as the elevation of the surface molecules such as
      CD28, PD-1, CTLA-4 and FasL and intracellular granzyme B. Selectively blocking
      the MOR by CTAP or DOR by NTI could result in inhibition of the corresponding
      CD8+T cells proliferation and the expressions of surface molecules. In addition,
      non-selectively blocking both MOR and DOR by NTX could further impair the
      functions and proliferation of CD8+T cells. Our currently data indicated that
      MENK could play a vital role in immune functions via precise regulation to
      subunits of opioid receptors.

PMID- 30290370
TI  - Potential cardiac consequences of thrombocytopenia and thrombocytosis.
AB  - This report illustrates the heart in three patients with cardiac hemorrhages
      associated with extreme thrombocytopenia, and the hearts in three patients with
      rocks speculated to result at least in part from organization of thrombi possibly
      related to thrombocytosis in one or more cardiac chambers.

PMID- 30290371
TI  - Men's Participation and Performance in the Boston Marathon from 1897 to 2017.
AB  - This study examined men's participation and performance in the Boston Marathon.
      Data from all 368,940 official male finishers in the Boston Marathon from 1897
      through 2017 were analyzed using different analyses and regression models for all
      runners, annual top hundred finishers, annual top ten finishers and annual
      winners. Effect of calendar year on race time was examined alone, in a uni
      variable model, and together with country of origin and weather conditions
      (average air temperature and precipitation) in a multi-variable model. The mean
      race time of all finishers increased across calendar years, in line with the
      participation, but it decreased when we considered the annual winners, 10 and 100
      fastest. Kenyans and Ethiopians were the fastest nationalities (p<0.001) when we
      considered all finishers and the annual top 100 fastest but not when the annual
      10 fastest were considered. Air temperature<=8  degrees C improved (p<0.001) race
      times compared to air temperature>8 degrees C. Precipitation (>0 mm) improved
      performance for the annual 100 fastest and annual 10 fastest (p=0.013-0.031) but
      not for all finishers. Our findings improved the knowledge about the evolution of
      male marathoners across calendar years, considering as main effects country of
      origin and particular weather conditions.

PMID- 30290372
TI  - Association of Monocarboxylate Transporter-1 (MCT1) A1470T Polymorphism
      (rs1049434) with Forward Football Player Status.
AB  - The aim of this study was to investigate the association between the MCT1
      (monocarboxylate transporter 1) A1470T polymorphism and positional roles in a
      large cohort of professional football players from five different countries. We
      compared genotype distributions of the MCT1 A1470T polymorphism between football
      players (n=694) and non-athlete controls (n=781) from Italy, Poland, Lithuania,
      Ukraine and Malta, and we analyzed the MCT1 genotype distributions with respect
      to the players' positions in the field (e. g. forwards, midfielders, defenders
      and goalkeepers). Genomic DNA was extracted from either buccal epithelium or
      peripheral blood using a standard protocol. In the pooled cohort of Italian,
      Polish, Lithuanian and Ukrainian football players, forwards (n=148) were more
      likely than controls (n=781) to possess the A allele (chi2=7.067, p=0.029, FDR q
      value 0.116), with a greater likelihood of having the AA genotype compared with
      the TT genotype (OR=1.97; C.I.=1.07-3.64; p=0.021, FDR q value 0.086). The MCT1
      AA genotype was significantly more frequent in forwards then in controls. Further
      studies are needed to confirm these findings in other professional football
      player cohorts.

PMID- 30290373
TI  - Plasma Steroids are Not Associated with Resting and Exercise Blood Pressure.
AB  - We investigated the associations between steroid hormones and resting and
      exercise blood pressure in the sedentary state and in response to an exercise
      program controlling for sex, body mass, ethnicity, age, oral contraceptives,
      hormone therapy, smoking and alcohol intake in subjects from the HERITAGE Family
      Study.: In the sedentary state, 267 men (28% Blacks) and 301 women (37% Blacks)
      were available, and 241 men and 254 women completed the exercise program.
      Fourteen steroid hormones and sex hormone-binding globulin concentrations were
      assayed in a fasted state. Statistical significance was set at a Bonferroni
      adjusted p<0.0001. After controlling for the various covariates, only
      testosterone came close to a significant correlation with exercise systolic blood
      pressure at 50 W (r=-0.21, P=0.0006) in men. No other correlations with resting
      and exercise blood pressure traits were found at baseline. There were significant
      changes in blood pressure in response to the exercise program, but none of the
      correlations with baseline plasma steroids reached statistical significance.
      Plasma steroids do not correlate with resting and exercise blood pressure in
      sedentary adults and do not associate with blood pressure changes in response to
      a 20-week endurance exercise program.

PMID- 30290374
TI  - Associations of the Force-velocity Profile with Isometric Strength and
      Neuromuscular Factors.
AB  - We aimed to explore relationships between the force-velocity (FV) profile and the
      isometric muscle torque performance during a knee extension task. The FV profile
      (force-intercept [F0], velocity-intercept [V0], maximum power [Pmax], and FV
      slope) during the countermovement jump (CMJ) exercise and isometric maximum
      voluntary torque (MVIC) and explosive voluntary torque production were assessed
      in 43 participants. Electromyography (EMG) was recorded during the isometric
      assessments and resting muscle architecture measurements were also performed
      (quadriceps thickness, vastus lateralis pennation angle and fascicle length).
      Pearson's correlation coefficients were computed to assess bivariate
      relationships between the FV profile, isometric torque, EMG activation and muscle
      architecture. F0 predictions from neuromuscular measurements were assessed
      through multiple linear regression. Associations of F0 and Pmax with isometric
      torque increased from explosive to MVIC torque (r>=0.47; P<0.05). Significant
      associations were found between muscle architecture and F0 and Pmax (r>=0.69;
      P<0.05), while V0 and FV slope were unrelated (r<=0.27; P>0.05). Quadriceps
      thickness and VL pennation angle explained ~62% of F0 variance. In conclusion,
      the knee extensors maximal isometric strength and their morphological
      architecture are strongly related to F0 estimated from a CMJ FV profile test.

PMID- 30290375
TI  - [Rehabilitants' Expectations and Informational Needs Concerning Inpatient
      Psychosomatic Rehabilitation - Results of a Qualitative Analysis].
AB  - AIM OF THE STUDY: In order to develop an online portal for the preparation for
      inpatient psychosomatic rehabilitation, information requirements as well as the
      online use behavior of rehabilitants were determined first. METHODS: Four focus
      groups with rehabilitants (N=31) as well as two with the treatment team (N=18)
      were performed and evaluated qualitatively. RESULTS: A total of 419 statements by
      rehabilitants and 333 statements by the treatment team were coded and assigned to
      categories. Current information materials on rehabilitation have been regarded as
      too extensive and difficult to understand by rehabilitants. They were uncertain
      regarding the effectiveness and sustainability of the treatment. While
      practitioners assumed that rehabilitants expect wellness and relaxation during
      rehabilitation, rehabilitants themselves reported more of an active treatment
      orientation. CONCLUSION: Online portals for preparation should address the
      effectiveness and sustainability of psychosomatic rehabilitation by means of
      illustrative case studies.

PMID- 30290376
TI  - [Current Endoscopic Methods in Bariatric Surgery].
AB  - The 2011 World Health Summit reported the epidemics of diabetes mellitus and
      morbid obesity. In Germany, 62.7% of the population have a BMI above 25 kg/m2 and
      21.9% above 30 kg/m2. 10.5 patients per 100,000 inhabitants were treated with
      metabolic surgery, whereas in France 86.0 and in Sweden 114.8 patients per
      100,000 inhabitants were given surgery. The development of endoscopic methods
      leads to the opportunity to bridge patients with a high risk profile before
      operation. Endoscopy is an excellent procedure with few complications. However,
      these methods need a selective and specialised concept of treatment. Endoscopy in
      metabolic surgery requires expertise in both endoscopy and in the techniques of
      metabolic surgery. The aim of the present paper is to report the new methods of
      endoscopy in the treatment of obese patients, on the basis of the literature and
      our own experience.

PMID- 30290377
TI  - Biological Actions, Electrical Conductance and Silicon-Containing Microparticles
      of Arsenicum Album Prepared in Plastic and Glass Vials.
AB  - INTRODUCTION:  According to the "silica hypothesis" formulated to explain
      homeopathy, the information of starting materials would be transferred to cells
      by silica nanoparticles detached from the glassware walls by serial dilution and
      agitation through epitaxy. We compared the biological activity, electrical
      current and silicon microparticle content (by means of scanning electron
      microscopy/energy-dispersive X-ray spectroscopy) of high dilutions (HDs) of
      arsenic prepared in plastic and glass vials to investigate the role of silica in
      their biological effects in vitro. MATERIALS AND METHODS:  Co-cultures of
      macrophages and yeast (Saccharomyces cerevisiae) were treated with different HDs
      of arsenic prepared in plastic and glass vials. Macrophage morphology,
      phagocytosis index, nitric oxide (NO), and cytokine production were evaluated.
      RESULTS:  Measurable amounts of silicon microparticles were detected only in the
      HDs prepared in glass vials, but ultra-centrifugation eliminated them. Specific
      and non-specific results were observed. Non-specific pro-inflammatory effects
      were seen in all dilutions prepared in plastic vials, including elevation of pro
      inflammatory cytokines, NO and macrophage phagocytic index. Only the 200th
      centesimal dilution of arsenic produced specific decrease in interleukin-6
      production in macrophages, and it was independent of the vial type or the
      presence of microparticles of silica in the medicine samples. The nature of the
      vials had an impact on the electric flow in the respective fluids. CONCLUSION: 
      The non-specific, pro-inflammatory effects might be attributed to organic
      residuals detached from the vials' plastic walls during manipulation. Instead,
      specific silica-independent effects of the homeopathic medicine can be attributed
      to the decrease of interleukin-6 after treatment with the 200th centesimal
      dilution of arsenic.

PMID- 30290378
TI  - Electronic Registration in Complementary/Homeopathic Medical Practice with
      Identification of 'Best Homeopathic Cases': A Pilot Study.
AB  - BACKGROUND:  Practice-based registration could identify 'general' and
      'homeopathic' prognostic factors for therapeutic success in patients who seek
      complementary and alternative medicine (CAM)/homeopathic treatment.
      Identification of 'best homeopathic cases' within a database could inform
      clinical research and improve homeopathic practice. OBJECTIVE: To investigate the
      feasibility of registration in daily CAM/homeopathic practice, evaluate patient
      reported outcome measures and tools for identifying 'best homeopathic cases' and
      to make recommendations for an electronic database. METHODS:  In 2015 and 2016,
      25 homeopathic doctors registered details of a maximum of 20 patients each, with
      6 months of follow-up (extended follow-up for 'best homeopathic cases'), in Excel
      or in the Homeopathic Administration and Registration Program (HARP) database.
      Informed consent was obtained from each patient. Patient-perceived change of main
      complaint was measured by a 7-point Likert scale. Best homeopathic cases were
      defined by treatment with one homeopathic medicine, >= 2 months of follow-up,
      result score +2 to +4 on a 9-point Likert scale by the doctor, and by changes
      that could be attributed to the homeopathic medicine. Association between scores
      for change of main complaint and scores for 'best homeopathic case' was analysed
      by the Kruskal gamma test. RESULTS:  Three-hundred and ninety-nine patients were
      included. In 49.1%, the main complaint was present for >= 2 years. The most
      common diagnosis was 'fatigue' (N = 56; 14%). Major improvement in the main
      complaint (score +3) was reported by 22 to 26% at consecutive follow-up visits.
      One-hundred and ninety-six patients were treated with a single homeopathic
      medicine, among whom 66 'best homeopathic cases' were identified. The correlation
      between patient-reported changes of main complaint and assessment by the doctor
      was significant (gamma = 0.832; p < 0.001). CONCLUSIONS:  Registration of (co
      )diagnoses, chronicity, treatments and outcomes in homeopathic practice with
      identification of 'best homeopathic cases' is feasible, using the tools provided.
      A user-friendly electronic database for efficient recording is recommended.

PMID- 30290380
TI  - ?

PMID- 30290379
TI  - Bilateral Globus Pallidus Internus Deep Brain Stimulation in a Case of
      Progressive Dystonia in Mohr-Tranebjaerg Syndrome with Bilateral Cochlear
      Implants.
AB  - INTRODUCTION:  A 28-year-old man presented with a history of sensorineural
      deafness since early childhood treated with bilateral cochlear implants (CIs). He
      showed signs of debilitating dystonia that had been present since puberty.
      Dystonic symptoms, especially a protrusion of the tongue and bilateral hand
      tremor, had not responded to botulinum toxin therapy. We diagnosed Mohr
      Tranebjaerg syndrome (MTS). METHODS AND MATERIAL:  Deep brain stimulation (DBS)
      of the bilateral globus pallidus internus was performed predominantly with
      stereotaxic computed tomography angiography guidance under general anesthesia.
      Electrophysiology was used to identify the target regions and to guide DBS
      electrode placement. RESULTS:  In the immediate postoperative course and
      stimulation, the patient showed marked improvement of facial, extremity, and
      cervical dystonia. More than 2 years after implantation, his dystonic symptoms
      had dramatically improved by 82%. DISCUSSION:  MTS is a rare genetic disorder
      leading to sensorineural deafness, dystonia, and other symptoms. The use of DBS
      for the dystonia in MTS was previously described but not in the presence of
      bilateral CIs. CONCLUSION:  DBS in MTS may be a viable option to treat
      debilitating dystonic symptoms. We describe successful DBS surgery, despite the
      presence of bilateral CIs, and stimulation therapy over 2 years.

PMID- 30290381
TI  - ?

PMID- 30290382
TI  - ?

PMID- 30290383
TI  - ?

PMID- 30290384
TI  - ?

PMID- 30290385
TI  - ?

PMID- 30290387
TI  - ?

PMID- 30290386
TI  - ?

PMID- 30290389
TI  - ?

PMID- 30290388
TI  - ?

PMID- 30290390
TI  - ?

PMID- 30290391
TI  - ?

PMID- 30290392
TI  - ?

PMID- 30290393
TI  - [Treatment of Acute and Chronic Ruptures of the Extensor Mechanism of the Knee
      Joints].
AB  - Ruptures of the extensor mechanism of the knee joint are rare but disabling
      injuries. Injuries occur on the basis of degeneration or acute trauma. The
      understanding of anatomy and biomechanical function plays an essential role for
      choosing the right diagnostic methods and initiating successful treatment.
      Besides clinical examination ultrasound is a cost efficient primary diagnostic
      measure. Additional MRI can be beneficial for partial tears or chronic ruptures.
      Non-operative treatment is suitable for minor partial ruptures with sustained
      function. The most common methods for reattachment of the quadriceps and patellar
      tendon are either sutures placed through transpatellar drill holes or the use of
      suture anchors. For chronic ruptures various methods have been shown to be well
      accomplished. Most commonly local tendon flaps or harvested tendon transplants
      have shown good clinical outcomes. Early primary repair leads to mainly good
      functional outcomes. The results of chronic disruptions of the extensor mechanism
      of the knee vary widely.

PMID- 30290394
TI  - Effects of Repeated Bouts of Exercise on the Hemostatic System.
AB  - Physical activity is beneficial for health, for example, by lowering the risk of
      cardiovascular events. However, vigorous exercise is associated with the
      occurrence of thromboembolic events and sudden cardiac death, in particular in
      untrained individuals. Whereas acute exercise is known to cause a hypercoagulable
      state, repeated exposure to (strenuous) exercise by means of training may
      actually condition the hemostatic response to exercise. To date, the effects of
      exercise training on blood coagulability and the underlying mechanisms have yet
      to be fully discerned. In this review, the authors provide an overview of
      existing literature on how training programs and training status influence
      hemostasis in healthy individuals. Furthermore, they present data of a pilot
      study in which we studied the effects of repetitive submaximal intensity cycling
      on procoagulant and anticoagulant processes. It is known that factor VIII (FVIII)
      and von Willebrand factor (VWF) increase after exercise, but we found that this
      increase in FVIII and VWF (antigen, propeptide, and VWF in active conformation)
      was smaller on each of three subsequent days, suggesting either adaptation of
      endothelial activation or exhaustion of endothelial VWF supplies. With respect to
      thrombin generation, elevated FVIII significantly increased the thrombin
      generation peak but not the endogenous thrombin potential. In contrast, platelet
      activation in terms of P-selectin expression after stimulation with protease
      activated receptor-1 and glycoprotein VI agonists decreased after exercise and
      did not recover, indicating exhaustion of the platelet response to repetitive
      exercise.

PMID- 30290395
TI  - [Assessment of the OPS Code 8918 Multimodal Pain Therapy].
AB  - Interdisciplinary multimodal pain therapy is the gold standard in the treatment
      of chronic pain. Due to an overall increase in case numbers, the number of MDK
      examinations leading to the assessment of primary incorrect occupancy is also
      increasing. This results in a multitude of social court disputes in which medical
      assessments are required. With knowledge of the legal norms and relevant
      guidelines or other recommendations, the expert can take this topic step by step.
      The starting point here is the evaluation of the patient file, followed by the
      examination of the medical indication, the implementation of the therapy and,
      finally, the answers to the questions of proof. A test scheme based on the
      Schroter concept can further simplify this process.

PMID- 30290396
TI  - Infraspecific Variation of Huperzine A and B in Icelandic Huperzia selago
      Complex.
AB  - The alkaloids huperzine A and huperzine B were originally isolated from the
      Chinese club moss Huperzia serrata. They are known inhibitors of
      acetylcholinesterase, and especially huperzine A shows pharmaceutical potential
      for the treatment of Alzheimer's disease. Its supply heavily relies on natural
      plant sources belonging to the genus Huperzia, which shows considerable
      interspecific huperzine A variations. Furthermore, taxonomic controversy remains
      in this genus, particularly in the Huperzia selago group. With focus on Icelandic
      H. selago taxa, we aimed to explore the relatedness of Huperzia species using
      multi-locus phylogenetic analysis, and to investigate correlations between
      huperzine A contents, morphotypes, and genotypes. Phylogenetic analysis was
      performed with five chloroplastic loci (the intergenic spacer between the
      photosystem II protein D1 gene and the tRNA-His gene, maturase K, ribulose-1,5
      bisphosphate carboxylase/oxygenase large subunit, tRNA-Leu, and the intergenic
      spacer region between tRNA-Leu and tRNA-Phe). Huperzine A and huperzine B
      contents were determined using an HPLC-UV method. The phylogenetic analysis
      suggests that previously proposed Huperzia appressa and Huperzia arctica should
      not be considered species, but rather subspecies of H. selago. Three genotypes of
      Icelandic H. selago were identified and presented in a haplotype networking
      diagram. A significantly (p < 0.05) higher amount of huperzine A was found in H.
      selago genotype 3 (264 - 679 ug/g) than genotype 1 (20 - 180 ug/g), where the
      former shows a typical green and reflexed "selago" morphotype. The huperzine A
      content in genotype 3 is comparable to Chinese H. serrata and a good alternative
      huperzine A source. Genotype 2 contains multiple morphotypes with a broad
      huperzine A content (113 - 599 ug/g). The content of huperzine B in Icelandic
      taxa (6 - 13 ug/g) is much lower than that in Chinese H. serrata (79 - 207 ug/g).

PMID- 30290397
TI  - Media Disaster Reporting Effects on Public Risk Perception and Response to
      Escalating Tornado Warnings: A Natural Experiment.
AB  - Previous research has evaluated public risk perception and response to a natural
      hazards in various settings; however, most of these studies were conducted either
      with a single scenario or after a natural disaster struck. To better understand
      the dynamic relationships among affect, risk perception, and behavioral
      intentions related to natural disasters, the current study implements a
      simulation scenario with escalating weather intensity, and includes a natural
      experiment allowing comparison of public response before and after a severe
      tornado event with extensive coverage by the national media. The current study
      also manipulated the display of warning information, and investigated whether the
      warning system display format influences public response. Results indicate that
      (1) affect, risk perception, and behavioral intention escalated as weather
      conditions deteriorated, (2) responses at previous stages predicted responses at
      subsequent stages of storm progression, and (3) negative affect predicted risk
      perception. Moreover, risk perception and behavioral intention were heightened
      after exposure to the media coverage of an actual tornado disaster. However, the
      display format manipulation did not influence behavioral responses. The current
      study provides insight regarding public perception of predisaster warnings and
      the influence of exposure to media coverage of an actual disaster event.

PMID- 30290398
TI  - Comparison of Decision Tree and Logistic Regression Models for Utilization in
      Sexual Assault Kit Processing.
AB  - To combat the influx of sexual assault kits (SAKs) that need to be tested, an
      exploration of data from Ohio's SAK Testing Initiative was carried out to
      identify variables that impact whether a SAK contains a probative DNA profile
      that is eligible for the Combined DNA Index System (CODIS) database. A validation
      study was completed to confirm the existence of variable relationships from the
      initial examination of data; new and modified statistical models were introduced
      to improve the predictive accuracy to determine if a SAK will contain at least
      one CODIS eligible DNA profile. Descriptive statistics from the validation data
      set confirmed conclusions about the effects of days between the assault and kit
      collection, the age of the victim, and consensual sex around the time of the kit
      collection for obtaining CODIS eligibility of DNA. The decision tree was selected
      as the best model.

PMID- 30290399
TI  - Innervation of the Epithelium and Lamina Propria of the Urethra of the Female
      Rat.
AB  - The aim of this study was to characterize the number, type and distribution of
      immunochemically identified nerves in epithelium and lamina propria of the female
      rat urethra. Urethras from female Sprague-Dawley rats (n = 12) were fixed, frozen
      and sectioned (8 MUm). Standard immunohistochemical techniques were used to
      identify putative nerves using the following antibodies: calcitonin gene related
      peptide (cgrp), neuronal nitric oxide synthase (nNos), tyrosine hydroxylase (TH)
      and vesicular acetylcholine transporter (vacht). The number, distribution and
      characteristics of all immunoreactive (IR) structures adjacent to the urethral
      epithelium and in the lamina propria was assessed. In the bladder, few cgrp-IR
      and vacht-IR fibers were associated with the urothelium or suburothelium of the
      lateral wall. In contrast, large numbers of vacht-IR, nNos-IR and cgrp-IR fibers
      were found close to the epithelium and subepithelium of the bladder neck and
      throughout the urethra. The number of cgrp-IR fibers was significantly higher in
      the urethra in comparison with the bladder neck. A population of undescribed cgrp
      IR cells associated with the bladder neck and proximal urethra has been
      characterized. Each of these cells appears to be associated with a nerve fiber.
      In the distal urethra, the number of peptidergic fibers penetrating the
      epithelium was significantly higher than the rest of the urethra. Clearly, this
      study has revealed a highly complex and heterogeneous network of putative
      afferent nerves fibers along the length of the urethra. These structural
      specializations need to be taken into account when probing the different
      functions of the urethra. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30290400
TI  - MiR-141-3p Suppresses Tumor Growth and Metastasis in Papillary Thyroid Cancer via
      Targeting Yin Yang 1.
AB  - MicroR-141-3p has been found to be downregulated in papillary thyroid carcinoma
      (PTC), while little is known about the cellular functions and precise signals
      elicited by miR-141-3p in PTC. The results of this study indicated that the
      expression of miR-141-3p was aberrantly down-regulated in PTC tissues and cell
      lines, compared with the adjacent normal tissues and normal thyroid epithelial
      cells. Furthermore, the miR-141-3p expression level was negatively associated
      with TNM stage and lymph node metastasis in PTC. Expression of miR-141-3p
      effectively inhibited cell growth, promoted apoptosis, and suppressed invasion in
      PTC cells. Meanwhile, miR-141-3p knockdown with miR-141-3p inhibitor reversed
      these effects. Consistent with the in vitro study, miR-141-3p also exhibited anti
      neoplastic activity in vivo. Moreover, the results revealed that miR-141-3p
      directly recognized the 3' untranslated region (3'UTR) of Yin Yang 1 (YY1) and
      negatively regulated the expression of YY1 at both protein and mRNA levels.
      Ectopic expression of YY1 could effectively abrogate the anti-metastatic and
      proapoptotic effects of miR-141-3p. In summary, the findings suggested that miR
      141-3p can act as a tumor suppressor in PTC and may be a potential therapeutic
      target for PTC treatment. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30290403
TI  - Deviation in TSH levels linked to increased risk of Alzheimer's in women.

PMID- 30290401
TI  - The changes of mitochondria in substantia nigra and anterior cerebral cortex of
      hepatic encephalopathy induced by thioacetamide.
AB  - Hepatic encephalopathy (HE) is a neuropsychiatric syndrome resulting from chronic
      or acute liver failure. Under the condition of hepatic encephalopathy, various
      factors such as reactive oxygen species (ROS), inflammatory factors, ammonia
      poisoning and amino acids alteration lead to changes of mitochondria. Selective
      depletion of damaged mitochondrion is essential for maintaining the morphology
      and function of mitochondria and cells. In this study, molecular biology analysis
      was used to analyze the mitochondrial morphology in the substantia nigra (SN) and
      anterior cerebral cortex (ACC) of the HE mice. The results revealed that the
      drp1, mfn1 and mfn2 increased in mRNA level of SN, which indicated the changes of
      mitochondrial morphology in HE mice. The drp1 and mfn2 genes were up-regulated,
      then, the Opa1 exhibited no significant change in the ACC of HE mice. Further
      study demonstrated that the mitochondrial autophagy related genes, pink1 and
      parkin, increased in SN, while the parkin reduced in ACC of HE mice. In addition,
      uncoupling protein (ucp2) increased in mRNA level of SN and ACC, and the ucp4 had
      no change or reduced in SN and ACC, respectively. These findings suggested that
      the mitochondrial dynamics is different in the substantia nigra and anterior
      cerebral cortex of hepatic encephalopathy mice. Therefore, our results indicated
      that mitochondrial dynamics provided a potential treatment strategy for hepatic
      encephalopathy through the fission, fusion and autophagy of genes. This article
      is protected by copyright. All rights reserved.

PMID- 30290404
TI  - Retinoids and the metabolic syndrome.

PMID- 30290405
TI  - Side effects of pulsatile GnRH therapy for induction of ovulation.

PMID- 30290406
TI  - Endoscopic trans-sphenoidal surgery for pituitary tumors.
AB  - Trans-sphenoidal surgery, which is the most widely used technique for the
      treatment of pituitary tumors, has continued to evolve by introducing new
      approaches and technologies, such as the direct endonasal route and the
      endoscope. The endonasal approach is a minimally invasive route to the sella
      turcica with the advantages of using a simpler and more rapid nasal dissection
      and eliminating the nasal and lip complications. Restricted exposure provided by
      the endonasal approach is overcome by combined use of an endoscope that provides
      a more panoramic view of the surgical field beyond the area covered by the
      operating microscope. An operating microscope permits binocular vision and
      bimanual technique, which are familiar to neurosurgeons. Neurosurgeons should
      exploit the advantages of both modalities for the benefit of patients. This
      review describes the advances in trans-sphenoidal surgery focusing on the
      endoscopic approach.

PMID- 30290407
TI  - Approaches to dyslipidemia treatment in children and adolescents.
AB  - Atherosclerosis represents a disease that begins in childhood, and alterations in
      lipid concentration play a fundamental role in the development of this condition.
      Children and adolescents with high cholesterol levels are more likely than their
      peers in the general population to present with dyslipidemia in adulthood.
      Precocious identification of dyslipidemias associated with premature
      cardiovascular disease is crucial during childhood to delay or prevent the
      atherosclerotic process. The National Cholesterol Education Program has
      established guidelines for the diagnosis and treatment of dyslipidemia during
      pediatric age. It has been suggested that a heart-healthy diet should begin at 2
      years of age, and no adverse effects on psychological aspects, growth, pubertal
      development and nutritional status in children and adolescents limiting total and
      saturated fat intake have been demonstrated. Pharmacotherapy should be considered
      in children aged 10 years or older when low-density lipoprotein cholesterol
      concentrations remain very high despite dietary therapy, especially when multiple
      risk factors are present. The lipid-lowering drugs recommended for childhood and
      adolescence are resins and statins. The increasing use of statins is dependent on
      their effectiveness and safety. Ezetimibe, a selective cholesterol absorption
      inhibitor, may provide a similar cholesterol-lowering effect as that reached with
      statin treatment. This review provides an update on recent advances in the
      therapy of dyslipidemia, especially hypercholesterolemia, during pediatric age
      and adolescence.

PMID- 30290408
TI  - Pendred syndrome.
AB  - Pendred syndrome (PDS) is an autosomal recessive disorder clinically
      characterized by sensorineural hearing loss and goiter. PDS is mainly caused by
      mutations in the SLC26A4 gene, although a few cases are due to mutations in the
      FOXI1 gene. SLC26A4 encodes pendrin, a sodium-independent transporter of
      iodide/chloride, chloride/formate and bicarbonate, that is expressed in the inner
      ear, thyroid gland, syncytiotrophoblast cells, endometrium and kidney. FOXI1
      encodes a transcription factor necessary for pendrin expression. Patients with
      PDS show a bilateral and severe-to-profound hearing loss, although some cases
      present with a slowly progressive and fluctuating course. Temporal bone
      abnormalities with enlargement of the vestibular aqueduct, alone or with Mondini
      dysplasia, are common. Goiter appears most frequently in the second decade of
      life with a range of variations in size, depending on the amount of iodide intake
      and the effect that the mutation causes in pendrin function in any individual
      patient. A standard thyroid hormone-replacement regimen should be given to PDS
      patients with hypothyroidism to re-establish euthyroidism and prevent or decrease
      goiter growth. Total or partial thyroidectomy is occasionally the treatment of
      choice. Hearing aids and proper educational programs should also be offered to
      patients.

PMID- 30290409
TI  - Role of calcium metabolism in premenstrual syndrome.
AB  - Premenstrual syndrome has been the subject of many myths and misconceptions over
      the centuries. It is a very common problem affecting millions of young women
      during their reproductive lives and is characterized by numerous recurrent,
      cyclical emotional and physical symptoms during the luteal phase of the menstrual
      cycle. The etiology of this disorder has remained poorly understood until only
      recently. Alterations in calcium homeostasis have long been associated with many
      affective disorders. Cyclical fluctuations of the ovarian steroid hormones across
      the menstrual cycle influence calcium metabolism, affect intestinal calcium
      absorption and modulate 1,25-dihydroxyvitamin D synthesis. Evidence now strongly
      suggests that abnormalities in calcium and vitamin D metabolism, specifically
      calcium and vitamin D deficiency, are responsible for these luteal-phase
      symptoms. Calcium and vitamin D supplementation may offer a simple solution to
      millions of women affected with premenstrual syndrome.

PMID- 30290410
TI  - Imaging of hyperfunctioning adrenal masses.
AB  - Adrenal imaging not only aims to detect hyperfunctioning adrenal lesions
      responsible for distinct clinical syndromes (pheochromocytoma, Cushing's syndrome
      or primary aldosteronism) but also to differentiate malignant from benign
      disease. Computed tomography (CT), MRI and high-resolution ultrasound imaging
      methods are available for detection of adrenal masses with high sensitivities.
      Although the risk of malignancy increases with the size of the adrenal mass, this
      criterion does not discriminate malignant from benign disease with sufficient
      specificity. Attenuation values on unenhanced CT, contrast washout
      characteristics on CT and chemical-shift imaging on MRI help differentiate
      adrenal adenomas and nonadenomas. Adrenal lesions with equivocal results on CT
      and MRI can be characterized further by functional nuclear medicine imaging.
      Radiopharmaceutical agents specifically detect masses derived from the adrenal
      cortex (e.g.,131I-6-iodomethyl-norcholesterol) and from the adrenal medulla
      (e.g., 123I- and 131I-meta-iodobenzylguanidine). Unspecific tracers, such as 18F
      fluorodeoxyglucose, are very useful in discriminating malignant and benign
      adrenal tumors.

PMID- 30290411
TI  - Human PAF complexes in endocrine tumors and pancreatic cancer.
AB  - The human RNA polymerase II-associated factor (hPAF) complex is comprised of five
      subunits that include hPaf1, parafibromin, hLeo1, hCtr9 and hSki8. This
      multifaceted complex was first identified in yeast (yPAF) and subsequently in
      Drosophila and humans. Recent advances in the study on hPAF have revealed various
      functions of the complex in humans that are similar to yPAF, including efficient
      transcription elongation, mRNA quality control and cell cycle regulation. A major
      component of the hPAF complex, hPaf1, is amplified and overexpressed in
      pancreatic cancer. The parafibromin subunit of the hPAF complex is a product of
      the hereditary hyperparathyroidism type 2 (HRPT-2) tumor-suppressor gene, which
      is mutated in the germ line of hyperparathyroidism-jaw tumor patients. This
      review evaluates the role of the hPAF complex and its individual subunits in
      endocrine and pancreatic cancers. It focuses on the functions of the hPAF complex
      and its individual subunits and dysregulation of the complex, thus providing an
      insight into its potential involvement in the development of endocrine cancers
      and other tumor types.

PMID- 30290412
TI  - Sphingomyelin synthases and testicular function.
AB  - Sphingomyelin synthase (SMS) is a cellular enzyme that catalyzes de novo
      synthesis of sphingomyelin (SM), which is a vital lipid component of cell
      membranes. Both members of the SMS family, SMS1 and SMS2, are found in mammalian
      testes and they are located in distinctive subcellular compartments, with SMS1 in
      the Golgi apparatus and SMS2 in the plasma membrane. At present, the precise
      function of SMS in the testis remains unknown. Recent studies have demonstrated
      an unique association of SMS2 with spermatids, particularly near developing
      acrosomes and the junction restructuring site at the apical ectoplasmic
      specialization (a testis-specific atypical adherens junction type) and Leydig
      cells in the rat testis. These data illustrate the possible involvement of SMS2
      in spermiogenesis and, perhaps, steroidogenesis in male reproductive function.
      This review summarizes the latest findings on SMS in the field, particularly its
      role in testicular function.

PMID- 30290413
TI  - Hypothalamic regulation of appetite.
AB  - The prevalence of obesity is steadily rising and has huge health and financial
      implications for society. Weight gain is due to an imbalance between dietary
      intake and energy expenditure and research has focused on trying to understand
      the complex pathways involved in controlling these aspects. This review
      highlights the key areas of research in the hypothalamic control of appetite. The
      hypothalamus consists of several nuclei that integrate peripheral signals, such
      as adiposity and caloric intake, to regulate important pathways within the CNS
      controlling food intake. The best characterized pathways are the orexigenic
      neuropeptide Y/Agouti-related protein and the anorexigenic pro
      opiomelanocortin/cocaine- and amphetamine-related transcript neurons in the
      arcuate nucleus of the hypothalamus. These project from the arcuate nucleus to
      other key hypothalamic nuclei, such as the paraventricular, dorsomedial,
      ventromedial and lateral hypothalamic nuclei. There are also projections to and
      from the brainstem, cortical areas and reward pathways, all of which influence
      food intake. The challenge at present is to understand the complexity of these
      pathways and try to find ways of modulating them in order to find potential
      therapeutic targets.

PMID- 30290415
TI  - Anti-estrogen therapy offers new hope for ovarian cancer patients.

PMID- 30290414
TI  - Identification, treatment and management of cardiovascular risks in patients with
      acromegaly.
AB  - Acromegaly, a syndrome related to growth hormone/IGF-1 excess, is frequently
      complicated by cardiovascular abnormalities (acromegalic cardiomyopathy).
      Extremely frequent are left ventricular hypertrophy and alterations of diastolic
      filling, which may progress to systolic dysfunction and eventually heart failure.
      Cardiac abnormalities may normalize after successful medical or surgical
      treatment of acromegaly, particularly in young patients with short-lasting
      disease, but this is less likely to occur in elderly patients. Both hypertension
      and cardiac valve disease are frequently encountered in acromegaly, but neither
      seems to be favorably influenced by disease control. The prevalence of coronary
      heart disease (CHD) is controversial but is probably not increased in acromegaly.
      Arrhythmias are relatively common in untreated acromegalic patients, although
      their clinical relevance is unknown. A cardiac evaluation of acromegalic patients
      should include echocardiography, basal electrocardiogram and blood pressure
      measurement, and evaluation of common risk factors for CHD. Appropriate and
      prompt treatment allowing a rapid control of growth hormone/IGF-1 hypersecretion
      is warranted because many features of acromegalic cardiomyopathy may be reverted,
      particularly in younger patients. In view of the lack of association with
      acromegaly, common risk factors for CHD, hypertension, arrhythmias or valve
      disease should be managed independently, irrespective of control of disease
      activity.

PMID- 30290416
TI  - Disparities in diabetes care among minority populations.

PMID- 30290417
TI  - Oral antidiabetic agents: how much kidney disease can we tolerate?
AB  - Type 2 diabetes mellitus and chronic kidney disease in mild and moderate stages
      is a common and underestimated comorbidity with relevant therapeutic
      consequences. Available oral antidiabetic agents are effectively used in keeping
      blood glucose levels within the guideline range but long lists of
      contraindications often limit their use. Chronic kidney disease is a very common
      reason to withhold or discontinue an oral antidiabetic therapy, precluding many
      patients from drugs with proven benefit, such as metformin. Often
      contraindications are not based on data but on theoretical grounds or expert
      opinion. In this review, we critically review threshold levels of kidney function
      for common oral antidiabetic agents, the evidence from which they were derived
      and offer advice on how to monitor kidney function as an important procedure in
      clinical practice.

PMID- 30290418
TI  - Noncoding miRNAs as key controllers of pancreatic beta-cell functions.
AB  - miRNAs, a recently discovered family of small noncoding RNAs, are emerging as
      major controllers of gene expression and key determinants of pancreatic beta-cell
      function. These 19-22-nucleotide molecules govern gene expression by partially
      pairing to 3'-untranslated regions of target mRNAs and by inhibiting their
      translation. The elucidation of the role of miRNAs promises to unravel new
      aspects of beta-cell biology and to clarify the mechanisms leading to defective
      insulin secretion in diabetes mellitus. This information is expected to favor the
      design of new approaches for preserving functional beta-cells in prediabetic
      stages and the development of strategies for engineering insulin-secreting cells
      capable of replacing endogenous beta-cells in diabetic patients.

PMID- 30290419
TI  - Role of radiolabeled octreotide therapy in patients with metastatic
      neuroendocrine neoplasms.
AB  - Peptide receptor radionuclide therapy is a new therapeutic modality for patients
      with nonresectable neuroendocrine tumors. The technique is based on the unique
      ability of these tumors to express cell membrane-specific peptide receptors that
      can be targeted with radiolabeled somatostatin analogues. A high level of uptake
      on somatostatin receptor scintigraphy is a prerequisite for effective treatment.
      The efficacy of this method has been proven in several clinical trials. In a
      substantial number of patients, an improvement of life quality has been achieved
      in addition to a marked morphologic and biochemical tumor response. Serious side
      effects are rarely observed. Attention must be paid to kidney protection during
      the treatment. The present review summarizes the clinical experience with the
      treatment of advanced neuroendocrine tumors with radiolabeled somatostatin
      analogues and focuses on patient selection and the appropriate timing of the
      therapy. Finally, it emphasizes treatment-related issues that deserve attention
      in the future.

PMID- 30290420
TI  - Challenges in studies of the genetic basis of Type 2 diabetes.
AB  - The prevalence of diabetes is increasing worldwide in epidemic proportions. This
      increase is mainly due to increased incidence and prevalence of Type 2 diabetes,
      which accounts for 80-90% of all cases of diabetes. The susceptibility to develop
      Type 2 diabetes is determined by genetic and environmental factors. Major genes
      responsible for Type 2 diabetes have not yet been identified. The most replicated
      susceptibility gene for Type 2 diabetes is TCF7L2, recently published by
      investigators from Iceland. The second most widely replicated association between
      a genetic variation and the risk of Type 2 diabetes is that of the Pro12Ala
      polymorphism in the peroxisome proliferator-activated receptor gamma2 gene.
      Furthermore, the common E23K polymorphism in the KCJN11 gene, encoding the ATP
      sensitive potassium-channel subunit Kir6.2, and variants in the calpain-10 gene
      have been associated with increased susceptibility to Type 2 diabetes in meta
      analyses. Several studies have investigated the possibility that rare, highly
      penetrant mutations in the maturity-onset diabetes of the young genes lead to
      monogenic diabetes, while common polymorphisms increase the susceptibility to
      Type 2 diabetes. Indeed, there is increasing evidence that single nucleotide
      polymorphisms in hepatic nuclear factor-4alpha are significantly associated with
      the risk of Type 2 diabetes. In this review, different approaches to identify
      susceptibility genes for Type 2 diabetes are discussed. In particular, the
      importance of prospective population-based cohort studies and prospective
      intervention studies are emphasized. Finally, genome-wide association studies
      using single nucleotide polymorphisms randomly spaced across the entire genome
      may be useful in the identification of susceptibility genes for Type 2 diabetes.

PMID- 30290421
TI  - AIP gene in pituitary adenoma predisposition.
AB  - Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP)
      gene were recently shown to cause susceptibility to pituitary adenoma
      predisposition. The purpose of this review is to briefly recapitulate the current
      knowledge on hereditary susceptibility to pituitary adenomas and what led to the
      identification of AIP as a novel predisposition gene. We will then concentrate on
      the data on AIP mutations and pituitary adenoma predisposition phenotype that
      have accumulated since the gene was identified. Major future challenges, as well
      as the possibilities for clinical practice based on this recent finding, will
      also be discussed.

PMID- 30290422
TI  - Renal hemodynamics in overweight and obesity: pathogenetic factors and targets
      for intervention.
AB  - Weight excess is a risk factor for progressive renal function loss, not only in
      subjects with renal disease or renal transplant recipients, but also in the
      general population. Considering the increasing prevalence of obesity worldwide,
      weight excess may become the main renal risk factor on a population basis, all
      the more so because the risk is not limited to morbid obesity, but is already
      apparent in the overweight range. The mechanism of the renal risk is
      multifactorial. In addition to the role of comorbid conditions such as
      hypertension and diabetes, current evidence supports a pathogenetic role for
      renal hemodynamics, specifically glomerular hyperfiltration, and also glomerular
      hypertension. Weight excess is associated with an elevated glomerular filtration
      rate and a less pronounced rise in renal plasma flow, resulting in an elevated
      filtration fraction. This suggests glomerular hypertension due to afferent
      efferent dysbalance, which impairs glomerular protection from systemic
      hypertension. Data in renal transplant recipients support the pathogenetic role
      of elevated glomerular pressure for long-term renal prognosis. Blockade of the
      renin-angiotensin-aldosterone system can reverse the renal hemodynamic
      abnormalities. The obesity-associated renal risk is unfavourably affected by high
      sodium intake. This may be due to the effects of sodium on blood pressure, which
      is often sodium-sensitive in obesity, but direct renal effects are also present.
      Interestingly, sodium restriction ameliorates overweight-associated
      hyperfiltration in overweight subjects. More focus on weight excess as a renal
      risk factor is warranted. Preventive measures should focus on weight excess as
      well as on specific protection against renal damage, by renin-angiotensin
      aldosterone system-blockade and moderate sodium restriction.

PMID- 30290423
TI  - Function of nuclear steroid receptors in apoptosis: role of ursodeoxycholic acid.
AB  - Nuclear steroid receptors such as the glucocorticoid and the mineralocorticoid
      receptors modulate apoptosis in different cell types through transactivation
      dependent and -independent mechanisms. They are involved in both the induction
      and prevention of apoptosis depending on cell type. However, it is unclear how
      nuclear steroid receptors can affect expression of the same gene in opposing ways
      for different cells. In addition to their function as modulators of gene
      expression, nuclear steroid receptors often act as nuclear transporters of other
      regulatory molecules, thus indirectly regulating several apoptosis-related genes.
      Curiously, nuclear steroid receptors are thought to cooperate with the
      antiapoptotic endogenous bile acid, ursodeoxycholic acid, to prevent programmed
      cell death. The next decade will almost certainly unveil the remarkable role of
      nuclear steroid receptors in modulating the life and death struggle of cells and
      organ systems in human development and function.

PMID- 30290424
TI  - Genetics and pharmacogenetics of estrogen response.
AB  - Estrogens are a steroid hormone group distributed widely in animals and human
      beings. Estrogens diffuse across cell phospholipidic membranes and interact with
      estrogen receptors. Their highest concentration is found in target tissues with
      reproductive function (breast, ovary, vagina and uterus). High estrogen levels
      are usually associated with tumor onset and progression, while loss of estrogen
      or its receptor(s) contributes to development and/or progression of various
      diseases (osteoporosis, neurodegenerative disease and cardiovascular disease).
      Despite the numerous efforts to highlight estrogen's mechanism of action, recent
      discoveries showed an unexpected degree of complexity of estrogenic response.

PMID- 30290425
TI  - Breathing disorders in Prader-Willi syndrome: the role of obesity, growth hormone
      treatment and upper respiratory tract infections.
AB  - Prader-Willi syndrome is a neurogenetic disorder characterized by a number of
      signs and symptoms, including muscular hypotonia in infancy, hypogonadism,
      obesity and short stature. Neurobehavioral abnormalities and cognitive impairment
      are common. In addition, breathing abnormalities have been described, including
      sleep-related breathing disorders, abnormal chemoreceptor sensitivity and
      pulmonary function abnormalities. Growth hormone treatment is now widely used in
      children with Prader-Willi syndrome to improve growth and body composition. Over
      the last 4 years, case reports have been published concerning unexpected death,
      many of which were related to respiratory abnormalities. This review focuses on
      breathing abnormalities in Prader-Willi syndrome individuals and the influence of
      obesity, growth hormone treatment and upper respiratory tract infections.

PMID- 30290426
TI  - The role of lanreotide Autogel(r) in the treatment of acromegaly.
AB  - Acromegaly is a rare disease, but all clinicians have to be aware of the
      diagnosis in order to minimize the negative consequences of increased levels of
      growth hormone and IGF-I, and the possible impact of a pituitary macroadenoma.
      Surgery remains the first-line therapy and may alleviate both hormonal excess and
      symptoms due to tumor mass effects. Postoperatively, however, many patients may
      need adjunctive therapy. Somatostatin analogs were marketed for clinical use in
      the 1980s. The depot formulations of the synthetic somatostatin analogs
      octreotide and lanreotide, octreotide acetate long-acting repeatable and
      lanreotide sustained release, were developed by incorporating the analogs into
      microspheres. The advantage of the new formulation of lanreotide, lanreotide
      Autogel(r), is the prefilled syringe of lanreotide and water. The choice of
      analog should be individualized for each patient based on level of efficacy,
      adverse event profile and preferred mode of administration. Approximately a third
      of acromegalic patients are resistant to the currently available somatostatin
      analogs. Monotherapy using cabergoline or pegvisomant is clinically available.
      Adding cabergoline to a somatostatin analog may be advantageous in selected
      patients and promising data exist regarding combination therapy with pegvisomant.
      Radiotherapy is still an option; however, although treating comorbidities and
      avoiding hypopituitarism is very important, radiotherapy should only be used for
      selected patients where treatment targets cannot be achieved by using the other
      therapies.

PMID- 30290427
TI  - Skeletal muscle AMP kinase as a target to prevent pathogenesis of Type 2
      diabetes.
AB  - The metabolic property of skeletal muscle is highly malleable and adapts to
      various physiological demands by shifting energy-substrate metabolism. Skeletal
      muscle metabolism has a significant impact on whole-body metabolism and substrate
      utilization. Glucose and lipids are the main oxidative fuel substrates in
      skeletal muscle, and their utilization is coordinated by complex regulatory
      mechanisms. In people with Type 2 diabetes, glucose uptake and lipid oxidation in
      skeletal muscle are impaired. These metabolic defects are coupled to impaired
      insulin signaling. Exercise increases glucose uptake and lipid oxidation by an
      insulin-independent mechanism. The AMP-activated protein kinase (AMPK) cascade is
      activated in response to metabolic stress and has therefore been implicated in
      the regulation of exercise-induced metabolic and gene regulatory responses. AMPK
      is a heterotrimeric complex composed of a catalytic alpha, and regulatory beta
      and gamma subunits. Selective regulation of AMPK in skeletal muscle may be
      achieved by targeting alpha1/beta2/gamma3 heterotrimeric complexes. Activation of
      AMPK enhances GLUT4 translocation of glucose uptake in skeletal muscle from Type
      2 diabetic patients and animal models of the disease by an insulin-independent
      mechanism. Transgenic overexpression of mutated forms of the AMPK gamma3 subunit
      provide evidence that activation of AMPK promotes lipid oxidation and prevents
      the development of skeletal muscle insulin resistance. Thus, AMPK provides a
      molecular entry point into novel regulatory pathways to enhance lipid and glucose
      metabolism in an effort to prevent and treat skeletal muscle insulin resistance
      associated with Type 2 diabetes.

PMID- 30290428
TI  - Increased risk of diabetes following kidney transplant.

PMID- 30290430
TI  - Nuclear receptors: at the heart of the biological crosstalk between metabolism
      and circadian rhythm.

PMID- 30290431
TI  - Role of testosterone in older men: recent advances and future directions.

PMID- 30290432
TI  - Role of HNF-1alpha and HNF-1beta on insulin, IGF-1 and other potential target
      genes.
AB  - Hepatocyte nuclear factor (HNF)-1alpha and HNF-1beta are transcription factors
      that regulate many target genes in various tissues including liver, pancreas and
      kidney. Heterozygous mutations in the HNF-1alpha and HNF-1beta genes result in
      maturity-onset diabetes of the young (MODY)3 and MODY5, respectively. The
      discovery of these 'hepatocyte nuclear factors' as MODY-responsible genes
      provided a breakthrough in the field of diabetes. Patients with HNF-1alpha and
      HNF-1beta mutations, as well as their model mice, show impaired pancreatic beta
      cell function. The mechanism of impaired beta-cell function and the target genes
      has been intensively investigated by considerable in vitro and in vivo studies.
      The insulin gene is one of the target genes of HNF-1alpha and HNF-1beta in the
      beta-cells, and may contribute to the diabetes. The IGF-1 gene is also regulated
      by HNF-1alpha and HNF-1beta, and its decreased expression may contribute to
      growth failure and impaired beta-cell proliferation. Mutations in HNF-1beta
      result in symptoms in multiple organs, including kidney and liver, and several
      target genes have been reported to be involved in the pathogenesis. HNF-1alpha
      and HNF-1beta may be one of the master regulators of hepatocyte and islet
      transcription, and further investigations by microarray and genome-scale analyses
      are providing information for the better understanding of the complex
      transcriptional network involving HNF-1alpha and -1beta.

PMID- 30290433
TI  - Phosphatonins: new hormones that control phosphorus homeostasis.
AB  - Phosphorus (Pi) plays an important role in nucleic acid synthesis, energy
      metabolism, bone mineralization and cell signaling, and is also present in
      sugars, phospholipids and phosphoproteins. Phosphate homeostasis is controlled by
      processes that regulate the intestinal absorption and renal excretion of Pi, and
      bone turnover. These processes are influenced by peptide and sterol hormones,
      such as parathyroid hormone and 1alpha,25-dihydroxyvitamin D (1alpha,25[OH]2D3).
      Recently, a new class of phosphate-regulating peptides has been discovered:
      phosphatonins. These factors, such as FGF-23, secreted frizzled-related protein
      4, matrix extracellular phosphoglycoprotein and FGF-7, are circulating peptides
      with potent phosphaturic activity. These peptides inhibit Na/Pi transporters in
      renal epithelial cells and, therefore, increase renal Pi excretion. In addition,
      FGF-23 and secreted frizzled-related protein-4 inhibit 25-hydroxyvitamin D 1alpha
      hydroxylase activity, reducing 1alpha,25(OH)2D3 synthesis and, thus, intestinal
      Pi absorption. Phosphatonins have been associated with hypophosphatemic diseases,
      such as tumor-induced osteomalacia, X-linked hypophosphatemic rickets, autosomal
      dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets
      and hyperphosphatemic disease (e.g., tumoral calcinosis). The aim of this article
      is to review the role of phosphatonins in Pi metabolism in normal and pathologic
      conditions and also to investigate the correlations among the various
      phosphatonins.

PMID- 30290434
TI  - Detection of medullary thyroid cancer: a focus on serum calcitonin levels.
AB  - Medullary thyroid cancer (MTC) is a neuroendocrine tumor derived from the C cells
      of the thyroid. C cells are responsible for the production of calcitonin, a
      sensitive and specific marker for MTC. Early detection of MTC is essential;
      overall survival from MTC is related to patient age, stage of disease and extent
      of surgical resection. Elevated preoperative serum calcitonin levels have been
      shown to predict the likelihood of biochemical remission postoperatively. The use
      of routine serum calcitonin measurements as a screening measure for MTC in
      patients with thyroid nodules has been advocated in Europe. To date, routine
      calcitonin measurement has not been widely practiced in the USA; a recent cost
      effectiveness analysis suggests routine serum calcitonin measurements in patients
      with thyroid nodules may be comparable to other widely accepted screening
      programs.

PMID- 30290435
TI  - Hypothyroxinemia of prematurity: cause, diagnosis and management.
AB  - Infants born at extreme prematurity are at a high risk of developmental
      disability. A major risk factor for disability is having a low level of thyroid
      hormone, described as hypothyroxinemia, which is recognized to be a frequent
      phenomenon in these infants. At present, there is uncertainty among clinicians
      regarding the most appropriate method of managing hypothyroxinemia of
      prematurity. The literature suggests that some, but not all, forms of thyroid
      supplementation may reduce the incidence of disability in infants born at extreme
      prematurity. There is a pressing need to confirm the benefit of treatment and to
      establish the optimal way to treat transient hypothyroxinemia in these infants.

PMID- 30290436
TI  - Thyroid-stimulating hormone/cAMP-mediated proliferation in thyrocytes.
AB  - Current research on thyrotropin-activated proliferation in the thyrocyte needs to
      be aimed at a better understanding of crosstalk and negative-feedback mechanisms
      with other proliferative pathways, especially the insulin/IGF-1-induced
      phosphoinositol-3 kinase pathway and the serum-induced MAPK or Wnt pathways.
      Convergence of proliferative pathways in mTOR is a hotspot of current research,
      and combined treatment using double class inhibitors for thyroid cancer may bring
      some success. New thyroid-stimulating hormone receptor (TSHR)-interacting
      proteins, a better picture of cAMP targets, a deeper knowledge of the action of
      the protein kinase A regulatory subunits, especially their interactions with the
      replication machinery, and a further understanding of mechanisms that lead to
      cell cycle progression through G1/S and G2/M checkpoints are areas that need
      further elucidation. Finally, massive information coming from microarray data
      analysis will prompt our understanding of thyroid-stimulating hormone-promoted
      thyrocyte proliferation in health and disease.

PMID- 30290437
TI  - Control of colon cancer development and progression by selected estrogen receptor
      modulators.
AB  - Estrogens behave as protective agents on the development of colorectal cancer,
      and hormonal-replacement therapy is associated with an increased survival rate in
      women with this disease, indicating that estrogenic therapy correlates with a
      better prognosis. The protective effect of estrogens on Fcolorectal cancer
      development and progression is presumably related to the expression of estrogen
      receptors in colon mucosa, with the estrogen receptor-beta isoform being the
      predominant one. This observation suggests that estrogen receptor-beta could have
      an inhibitory effect on colorectal cancer cell proliferation and a regulatory
      effect on colonic mucosa cell growth, opening the discussion on a pharmacologic
      approach to colorectal cancer prevention and therapy based on estrogenic
      compounds.

PMID- 30290438
TI  - Transcriptional control of the expression of MUC1.
AB  - MUC1 is a multifunctional cell surface glycoprotein that modulates cell adhesion,
      protects mucosa from infection and enzymatic attack, lubricates cell surfaces,
      participates in multiple signal-transduction pathways and is overexpressed by
      many tumors. MUC1 levels change dynamically in various cellular contexts. The
      primary mechanism for controlling MUC1 expression appears to be transcriptional
      through a complex combination of often overlapping regulatory motifs that control
      both tissue specificity and overall rate of transcription. This review will
      summarize the current knowledge of the factors known to control MUC1
      transcriptional regulation, including cytokines, steroid hormones and the growth
      factors they stimulate, as well as suggest how this information may be exploited
      in the future to control MUC1 expression in specific biological contexts.

PMID- 30290440
TI  - Study results suggest that hypothalamic amenorrhea may have a genetic basis in
      some women.

PMID- 30290439
TI  - STAT5 activity in pancreatic beta-cells.
AB  - Signal transducer and activator of transcription (STAT)5A and -5B are latent
      transcription factors activated by cytokines and hormones of the cytokine family.
      In pancreatic insulin-secreting beta-cells, STAT5A and -5B are activated
      primarily by prolactin and growth hormone stimulation and are important mediators
      of the potent stimulation of proliferation and insulin production caused by these
      hormones. STAT5A and -5B are both expressed in beta-cells and control the
      expression of a number of mRNAs implicated in cell replication control, insulin
      biosynthesis and secretion. In addition to STAT5A and -5B being transcriptional
      activators, they may also repress gene transcription. By these means, STAT5
      proteins increase the levels of anti-apoptotic transcripts in beta-cells and
      repress expression of pro-apoptotic genes. This review focuses on the anti
      apoptotic role of STAT5 signaling, providing a mechanism for beta-cell resistance
      to pro-apoptotic cytokines, Type 1 diabetes mellitus and obesity-associated beta
      cell stress. It is clear from studies of STAT5 signaling in pancreatic beta-cells
      that STAT5 is important for postnatal beta-cell compensatory growth (as in
      pregnancy or obesity) and in the defense against beta-cell stress factors.

PMID- 30290441
TI  - A comparison of strontium ranelate and PTH(1-84).
AB  - Evaluation of: Quesada-Gomez JM, Muschitz C, Gomez-Reino J, Greisen H, Andersen
      HS, Dimai HP. The effect of PTH(1-84) or strontium ranelate on bone formation
      markers in postmenopausal women with primary osteoporosis: result of a
      randomized, open-label trial. Osteoporosis Int. DOI: 10.1007/s00198-010-1460-6
      (2010) (Epub ahead of print). A recent article compared parathyroid hormone
      (PTH[1-84]) and strontium ranelate with respect to their effects on bone
      formation and bone resorption markers, a study performed with the aim of shedding
      light on the potential differences in the mode of action of these two compounds.
      This study found that PTH(1-84) induces robust inductions of both the bone
      formation markers N-terminal propeptide of type I collagen and alkaline
      phosphatase, and the resorption marker c-terminal crosslinked telopeptide of type
      I collagen (CTX-I), data that correlate well with previous publications. However,
      for strontium ranelate, no induction of markers was observed. Furthermore,
      although the data were not significant, serum calcium levels in the two treatment
      groups exhibited opposing trends, with PTH(1-84) increasing these as expected and
      with strontium ranelate decreasing them. These data indicate that strontium
      ranelate utilizes another mode of action to the induction of turnover seen with
      PTH(1-84). Finally, a trend towards improved quality of life was seen with PTH(1
      84), while strontium ranelate did not change these parameters. This article is a
      useful addition to the ongoing debate on how best to possibly treat osteoporosis.

PMID- 30290442
TI  - Variability in stress system regulatory control of inflammation: a critical
      factor mediating health effects of stress.
AB  - Chronic stress has been associated with disease but the biological pathways are
      not completely understood. Stress systems such as the hypothalamus-pituitary
      adrenal axis and the autonomic nervous system are prime candidates but
      alterations in their baseline activity are not consistently found in chronic
      stress. Evidence suggests that stress-related changes in the sensitivity of
      inflammatory pathways towards glucocorticoid regulation, that is, the development
      of glucocorticoid resistance, might help explain inflammatory disinhibition and
      the subsequent development of disease. Recent data show a similarly important
      role for sympathetic and parasympathetic modulation of the inflammatory cascade
      for the maintenance of health. This article argues that variation of target
      tissue sensitivity towards anti-inflammatory effects of the hypothalamus
      pituitary-adrenal axis, as well as sympathetic and parasympathetic signaling,
      might be involved in the development of low-grade inflammation under chronic
      psychosocial stress.

PMID- 30290443
TI  - Intraoperative adjuncts for parathyroid surgery.
AB  - In recent years, parathyroid surgery has evolved from traditional bilateral neck
      exploration to minimal invasive parathyroidectomy. This trend became possible due
      to preoperative localization imaging that guides the surgeon in the search for a
      parathyroid adenoma. Intraoperative adjuncts are complementary to preoperative
      localization and assist in localizing parathyroid glands, confirming parathyroid
      tissue and establishing a cure. Institutions and surgeons utilize different
      intraoperative adjuncts in different protocols with varying results. The purpose
      of this article is to review the available intraoperative adjuncts to parathyroid
      surgery and critically evaluate their utility, accuracy and their added value to
      the surgeon.

PMID- 30290444
TI  - The efficacy and safety of vildagliptin in the GALIANT trial: chronic kidney
      disease and other applications.
AB  - The number of mechanistically novel antidiabetes agents has dramatically
      increased over the past few years. Dipeptidyl peptidase-4 (DPP-4) inhibitors in
      particular have emerged as clinically efficacious oral agents for diabetes
      management with a low incidence of side effects. The Galvus in Addition to
      Metformin versus Tzd/Metformin in Lowering HbA1c (GALIANT) trial showed that
      vildagliptin as an add-on therapy was noninferior to thiazolidinedione therapy
      with regard to reduction in hemoglobin A1c, with both drugs having a similar
      incidence of side effects in patients with normal and impaired renal function.
      DPP-4 inhibitors have a low incidence of hypoglycemia without significant weight
      gain and there is strong evidence that the administration of vildagliptin results
      in improved alpha- and beta-cell function. New data suggest that DPP-4 inhibitors
      might also have a role in the setting of myocardial infarction and lipid
      management, and in the prevention of Type 2 diabetes.

PMID- 30290445
TI  - Osteocalcin: an endocrine link between bone and glucose metabolism.
AB  - Impaired glucose metabolism is common and contributes to the risk of diabetes and
      cardiovascular disease. Deletion of the gene for the osteoblast-derived protein,
      osteocalcin, leads to insulin resistance in mice, while the addition of
      osteocalcin increases insulin secretion from beta-cells and adiponectin
      expression in adipocytes. Osteocalcin deficiency in gamma-carboxyl groups,
      undercarboxylated osteocalcin, was found to improve insulin secretion and
      sensitivity in experiments. Recent studies have examined the relevance of these
      findings to glucose metabolism and cardiovascular risk in humans. Low total
      osteocalcin levels are associated with insulin resistance, diabetes and metabolic
      syndrome in observational studies. New therapeutic approaches to diabetes and
      heart disease may be anticipated if this bone-derived protein is involved in the
      regulation of glucose metabolism and cardiovascular risk.

PMID- 30290446
TI  - Physiological effects of Type 2 diabetes on mRNA processing and gene expression.
AB  - Characteristics of Type 2 diabetes include both high blood glucose
      (hyperglycemia) and raised cholesterol and triglycerides (hyperlipidemia).
      Several studies have now shown that both hyperglycemia and hyperlipidemia can
      alter gene expression by disrupting physiological mechanisms of gene regulation,
      including alternative mRNA splicing, epigenetic gene regulation and miRNA
      mediated regulation of gene expression. These processes may also be influenced by
      intracellular oxidative stress, which is increased in diabetes and in response to
      hyperglycemia and hyperlipidemia. Many pathways relevant to diabetes are affected
      by altered gene expression, including lipid and glucose metabolism and oxidative
      phosphorylation. This article considers how hyperglycemia and hyperlipidemia can
      alter gene expression in diabetes, which could potentially contribute to the
      worsening of the diabetic phenotype and diabetic complications.

PMID- 30290447
TI  - Gender differences in thyroid cancer: a critical review.
AB  - It has long been known that the incidence of thyroid cancer in women is
      significantly higher than that in men. The objective of this article is to review
      gender differences in thyroid cancer, as well as epidemiological, clinical and
      experimental research on the role of sex hormones, their receptors and other
      molecular factors in this well-established thyroid cancer gender discrepancy.
      Although more common in women, thyroid cancer typically presents at a more
      advanced stage and with a worse disease prognosis in men. Clinical evidence on
      the impact of estrogen and other sex hormones on thyroid cancer has remained
      inconclusive, although numerous experimental studies have suggested that these
      hormones and their receptors may play a role in tumorigenesis and tumor
      progression. Studies of thyroid cancer cell lines suggest that an imbalance
      between the two estrogen receptor (ER) isoforms, alpha and beta, may be
      responsible for the cell proliferation seen with estrogen treatment. Expression
      studies on thyroid tumors indicate that they express ER and possibly progesterone
      receptors and androgen receptors, but there is conflicting evidence as to whether
      or not there is a difference in receptor status between thyroid cancers, benign
      thyroid lesions and normal thyroid tissue. There have been few studies evaluating
      the ERalpha/ERbeta profiles in thyroid tumors and normal thyroid tissue. Our
      understanding of the underlying basis for sex differences in thyroid cancer has
      improved over the last few decades, but the relationship between gender and
      thyroid cancer risk has remained elusive. Areas for future research include
      ERalpha/ERbeta profiling of normal and neoplastic thyroid tissue, association
      between ER status and tumor dedifferentiation, and evaluation of the signaling
      pathways by which estrogen and other sex steroids exert their effects on thyroid
      cancer cells. Sex steroid receptors, and then downstream signaling pathways,
      represent promising future therapeutic targets for thyroid cancer treatment, and
      further study is required.

PMID- 30290449
TI  - Oral contraceptives in polycystic ovarian syndrome: the long and short of it.

PMID- 30290450
TI  - Postradiation therapy hypopituitarism.
AB  - The increasing use of radiation treatment for head and neck cancers and other
      tumors, including pituitary adenomas, from the mid-20th Century onwards led to
      the recognition that pituitary function may be affected - often leading to some
      degree of pituitary insufficiency. Our knowledge is mostly based on observational
      or retrospective rather than randomized prospective studies. The various axes may
      be impacted at the hypothalamic or pituitary levels, or both. Some axes - the
      somatotropic and gonadotropic - appear to be especially vulnerable to radiation
      damage and may be affected quite early, whereas posterior pituitary function is
      rarely affected. Increased use of stereotactic radiosurgery, which focuses the
      radiation dose on the abnormal tissue, may be expected to reduce the impact on
      normal pituitary function, but such studies that are available are, as yet,
      relatively short term. Prospective studies of the effect of stereotactic
      radiosurgery on pituitary function would be valuable.

PMID- 30290451
TI  - Genetic susceptibility in pituitary adenomas: from pathogenesis to clinical
      implications.
AB  - Pituitary adenomas usually present sporadically, with a multifactorial
      pathogenesis including somatic mutational events in cancer-related genes. Genetic
      predisposition implies the presence of germline DNA alterations with a range of
      impacts on pituitary cell biology, translating into a variable penetrance of the
      disease. Genetic causes must be considered in the presence of specific clinical
      settings, such as familial occurrence of pituitary adenoma, with or without
      extrapituitary diseases, and may also be suspected in young patients (<30 years
      of age) with macroadenomas. We review the clinical implications of genetic
      predisposition, with special attention on multiple endocrine neoplasia type 1,
      Carney complex and familial isolated pituitary adenoma. Genetic screening in
      selected patients with an apparently sporadic disease is also discussed.

PMID- 30290453
TI  - Bremelanotide: the female Viagra?

PMID- 30290452
TI  - Osteoporosis following organ transplantation: pathogenesis, diagnosis and
      management.
AB  - Organ transplantation has become popular for the management of various chronic
      illnesses. With the advent of modern immunosuppressive treatments, the longevity
      of transplant recipients has increased. Consequently, morbid complications such
      as osteoporosis and bone fractures are seen at an increasing frequency in this
      population. In most transplant recipients, bone mineral density (BMD) falls
      shortly after transplantation. However, bone fracture rate plateaus in all except
      for post-renal transplant patients. Although the underlying pathophysiologic
      mechanism for this difference is not fully understood, potential mechanisms for
      sustained bone loss in renal transplant recipients may be persistent phosphorus
      wasting and defective bone mineralization. Current treatment regimens are based
      on studies in a small numbers of subjects with BMD as the primary outcome.
      Although BMD is recognized as a gold standard in the assessment of bone fracture
      risk, to date, its association with bone fracture risk in the general post
      transplant population is not robust. Therefore, randomized controlled trials with
      bone fracture as the primary end point are crucial. The development of
      noninvasive bone markers in distinguishing bone turnover and bone mineralization
      status is also pivotal since skeletal lesions are heterogeneous in various organ
      transplantations. The elucidation of these underlying skeletal lesions is
      necessary for the consideration of selective treatment in this population.

PMID- 30290454
TI  - Ion channels of primate ovarian endocrine cells: identification and functional
      significance.
AB  - Ion channels are crucially involved in cellular functions, but little is known
      about molecular identity, subunit composition and the specific role of ion
      channels in ovarian endocrine cells in human and nonhuman primates. Using human
      luteinizing granulosa cells, a few groups have started to address these questions
      and have begun to show molecular identity of ion channels, electrophysiological
      functions and the relationship to hormone production, as well as regulation by
      hormones and intraovarian factors. Functional ion channels that have been
      identified so far include T- and L-type Ca2+ channels (Cav3.2, Cav1.2), a voltage
      dependent Na+ channel (Nav1.7), as well as voltage- (Kv4.2) and Ca2+-dependent K+
      channels (BKCa). Since all these ion channels were found to be involved in
      steroid hormone synthesis and are expressed by endocrine ovarian cells in human
      and nonhuman ovary, it has been proposed that they are physiological key
      molecules for ovarian function. Furthermore, they may be novel targets for
      modulating ovarian functions.

PMID- 30290455
TI  - Proteomics for diabetes research: an update and future perspectives.
AB  - Diabetes is a common disease worldwide and can cause several complications,
      leading to systemic derangements and end-organ damage. Despite blood sugar
      control and adequate therapy with currently available drugs, diabetic
      complications remain a serious issue in clinical practice, indicating that our
      knowledge of diabetes and its complications is only at the tip of the iceberg.
      Better understanding of its pathogenesis and pathophysiology is crucial to
      achieve better therapeutic outcomes and to prevent its complications. This review
      provides an overview of proteomics and introduces proteomic technologies commonly
      used for diabetes research. Recent proteomic studies for the investigation of
      diabetes and its complications are summarized. Finally, the future perspectives
      for the field of proteomics in diabetes research are discussed.

PMID- 30290456
TI  - Obesity, insulin resistance, Type 2 diabetes and free fatty acids.
AB  - High levels of free fatty acids have emerged as a major link between obesity and
      insulin resistance/Type 2 diabetes. In pancreatic beta cells, free fatty acids
      potentiate glucose-stimulated insulin secretion precisely to the extent needed to
      compensate for the free fatty acid-induced insulin resistance. It is postulated
      that this prevents the development of Type 2 diabetes mellitus in the majority of
      obese, insulin-resistant individuals who have free fatty acid-mediated insulin
      resistance. In individuals with inherited defects of beta-cell function
      (prediabetics), this compensation fails and hyperglycemia develops. Elevated
      levels of free fatty acids also activate the proinflammatory and proatherogenic
      nuclear factor kappaB pathway. Thus, elevated plasma levels of free fatty acid in
      obese people can produce a low-grade inflammatory state, which may contribute to
      accelerated atherosclerosis (coronary artery disease, strokes and peripheral
      arterial disease) and to nonalcoholic steatohepatitis; these conditions are
      increased in obesity.

PMID- 30290457
TI  - Syndrome of inappropriate antidiuresis.
AB  - The syndrome of inappropriate antidiuresis is the most common cause of euvolemic
      hyponatremia and complicates a wide spectrum of diseases and neurosurgical
      conditions. The syndrome is characterized by clinical euvolemia, dilute plasma
      osmolality and inappropriately concentrated urine, with normal renal, adrenal and
      thyroid function. Hyponatremia in syndrome of inappropriate antidiuresis
      represents an excess of plasma water, rather than sodium deficiency. The severity
      of hyponatremia is limited by renal escape from antidiuresis. Treatment varies
      according to symptoms, severity and speed of onset of hyponatremia. Acute,
      severe, symptomatic hyponatremia may require rapid treatment with hypertonic
      saline, with care to avoid central pontine myelinosis. Chronic hyponatremia is
      managed with fluid restriction and demeclocycline for unresponsive cases.
      Vasopressin antagonists represent a new option for chronic hyponatremia of
      syndrome of inappropriate antidiuresis.

PMID- 30290458
TI  - Targeting 11beta-hydroxysteroid dehydrogenase type 1 in brain: therapy for
      cognitive aging?
AB  - Dementia care costs exceed those of cardiovascular diseases and cancer combined.
      Milder forms of functionally significant cognitive decline add further to the
      staggering human, societal and economic costs. However, the underlying mechanisms
      are poorly understood and few treatments are available. Cumulative exposure to
      high glucocorticoid levels is a major hypothesis of decline in cognitive function
      with aging. Current manipulations to maintain low circulating glucocorticoid
      levels throughout life (adrenalectomy with low-dose corticosterone replacement
      and neonatal handling), although effective in preventing the emergence of memory
      deficits with age in rodent models, are not clinically applicable. By contrast,
      recent data in cells, mice and humans suggest that inhibition of the tissue
      selective glucocorticoid-amplifying enzyme, 11beta-hydroxysteroid dehydrogenase
      type 1, may be an effective novel approach.

PMID- 30290459
TI  - Endocannabinoid system and its role in energy regulation.
AB  - Endocannabinoids are endogenous agonists for the two types of cannabinoid
      receptors identified to date, the CB1 and CB2 receptors. CB1 receptors and tissue
      concentrations of endocannabinoids sufficient to activate them are present in the
      brain structures controlling energy intake (i.e., the hypothalamus, nucleus
      accumbens and nodose ganglion), as well as in all peripheral organs mostly
      involved in the regulation of energy homeostasis (i.e., the duodenum, small and
      large intestine, adipose tissue, skeletal muscle, pancreas and liver). Several
      peripheral neuropeptides and hormones involved in energy balance, and type of
      diet, regulate endocannabinoid levels, whereas endocannabinoids, in turn,
      regulate the expression and release of hypothalamic mediators involved in
      nutrient intake. Dysregulation of the endocannabinoid system might contribute to
      the development of eating disorders and explain why CB1 receptor blockers are
      efficacious at reducing not only food intake but also the metabolic consequences
      of visceral adiposity and obesity.

PMID- 30290460
TI  - Role of inhaled human insulin in the management of Type 1 and 2 diabetes.
AB  - Inhaled human insulin (Exubera(r)) has been approved by the FDA and other
      regulatory bodies for treatment in Type 1 and 2 diabetes in the USA. It is the
      first alternative to injectable insulin since the discovery of the insulin
      compound to treat diabetes. This article will review results of recent clinical
      studies that support the therapeutic efficacy and safety of inhalable insulin for
      use in patients with diabetes. The pharmacological profile of inhaled insulin
      with particular reference to inhaled human insulin and the potential to influence
      diabetes care is also discussed.

PMID- 30290461
TI  - Neuroactive steroids as modulators of depression and anxiety.
AB  - In addition to the well-known genomic effects of steroid molecules, certain
      neuroactive steroids control neurotransmission through the modulation of specific
      neurotransmitter receptors. Preclinical studies suggested that neuroactive
      steroids may modulate anxiety and depression-related behavior and may contribute
      to the therapeutic effects of antidepressant drugs. However, nonpharmacological
      antidepressant treatment strategies did not affect neuroactive steroid
      composition. These studies suggest that the changes in neuroactive steroids
      observed after antidepressant pharmacotherapy probably reflect distinct
      pharmacological properties of antidepressants, rather than the clinical response.
      Nevertheless, initial studies investigating the antidepressive effects of
      exogenously administered dehydroepiandosterone revealed promising results. In
      addition, in various anxiety disorders, alterations of neuroactive steroid levels
      have been observed. In conclusion, neuroactive steroids contribute to the
      pathophysiology of affective disorders and the mechanisms of action of
      antidepressants. They are important endogenous modulators of depression and
      anxiety and might offer new targets for the development of novel anxiolytic
      compounds.

PMID- 30290462
TI  - Report on the 2nd Annual Metabolic Diseases World Summit.

PMID- 30290463
TI  - Rapid-acting insulin glulisine: a new tool for postprandial glucose control.
AB  - Insulin glulisine (Apidra(r), Sanofi-Aventis) is a novel, rapid-acting insulin
      analog that replicates normal mealtime insulin secretion more closely than
      regular human insulin. Compared with regular human insulin, glulisine has a more
      rapid onset of action and shorter duration of effect, affording greater
      flexibility in the timing and content of meals. Additionally, optional pre- or
      postmeal administration makes glulisine well suited for patients who eat
      erratically or have difficulty remembering premeal injections. This attribute is
      clinically relevant because addressing postprandial hyperglycemia may help
      attenuate cardiovascular morbidity and mortality among diabetic patients. Insulin
      glulisine is safe when used for pump therapy and its rapid-acting properties are
      maintained consistently across patient types and body mass indices, making it an
      effective and versatile tool for postprandial glucose control.

PMID- 30290464
TI  - Pegvisomant therapy for acromegaly.
AB  - Despite traditional, multimodality therapy that consisted of surgery,
      radiotherapy and medical therapies, many patients with acromegaly could not be
      adequately treated. Pegvisomant is a novel growth hormone receptor antagonist
      that became available for the treatment of acromegaly in 2003. This drug is a
      growth hormone variant that has nine mutations to human growth hormone. These
      give it high affinity for the growth hormone receptor as well as disrupting
      growth hormone receptor dimerization, with the net effect being antagonism of
      growth hormone at its receptor. Traditional methods of therapy for acromegaly
      treat the disease by reducing pituitary tumor secretion of growth hormone and,
      thus, lowering serum insulin-like growth factor-I levels. Pegvisomant, by
      contrast, blocks the actions of circulating growth hormone excess, but does not
      lower serum growth hormone levels. Its efficacy, therefore, is assessed by
      monitoring serum insulin-like growth factor-I levels. In clinical trials,
      pegvisomant has been shown to effectively normalize insulin-like growth factor-I
      levels in up to 97% of patients and to improve acromegaly-related signs and
      symptoms, and morbidities such as insulin resistance. As the action of
      pegvisomant does not rely on the tumor's receptor profile, it can be effective
      even in patients resistant to somatostatin analog therapy. Individually tailored
      therapy guided by serum insulin-like growth factor-I normalization goals and
      improvement in clinical signs and symptoms should be undertaken while growth
      hormone deficiency should be avoided. Pegvisomant is very well tolerated, but
      liver transaminase levels need to be monitored during therapy. As pegvisomant
      does not shrink pituitary tumors, the underlying rate of tumor growth may
      continue on this therapy and periodic pituitary imaging needs to be conducted
      during therapy.

PMID- 30290465
TI  - Sleep loss, obesity and diabetes: a fatal connection?

PMID- 30290466
TI  - Potential new diabetes treatment discovered during study of leptin.

PMID- 30290467
TI  - How growth hormone may be linked to cancer: concerns and perspective.
AB  - Recent evidence from epidemiology indicates that inter-individual variations in
      the growth hormone (GH)/IGF-I pathway affect the risk of individuals developing
      common epithelial cancers. This is supported by associations between normal
      common variants within genes from the pathway and these cancers, which excludes
      many potential confounding issues, such as reverse causality. This raises concern
      for the increasing numbers of patients treated with GH; although replacement
      therapy for GH-deficiency should aim to restore normality, which should then only
      incur a normal risk. The links with cancer also offers promising new
      opportunities. Clinical trials treating cancer patients with pharmaceuticals
      targeting the IGF-I receptor are well advanced with promising initial findings.
      In the future, there has to be much more emphasis within oncology on prevention
      and the GH/IGF-I pathway is one of few identified risk factors that are
      modifiable, not just by pharmaceutical, but also nutritional, interventions that
      may, in the long term, be more appropriate. Assessing the status of the GH/IGF-I
      pathway in individuals may also provide a means for targeting screening programs
      and preventative measures.

PMID- 30290468
TI  - Phenylketonuria: questioning the gospel.
AB  - Phenylketonuria (PKU) was first described over 70 years ago, treatment was
      developed 50 years ago and universal newborn PKU screening was introduced 40
      years ago. Phenylalanine-restricted dietary treatment has prevented mental
      retardation in thousands of individuals worldwide. We acknowledge, however, that
      there is still much to learn in the field. The incidence of mental retardation in
      untreated PKU is likely to be considerably less than the original estimates.
      Since dietary control is suboptimal in late childhood, adolescence and adulthood,
      alternative methods of treatment are being explored. These include large neutral
      amino acids, phenylalanine ammonia lyase, tetrahydrobiopterin and gene
      replacement. Evidence has surfaced that the semisynthetic, low-protein diet used
      to treat PKU may be deficient in certain important nutrients. Maternal PKU
      treatment may be successful even if initiated as late as 8-10 weeks into
      pregnancy. A plea is made for the immediate establishment of adult treatment
      centers for PKU (and other inherited metabolic diseases) for long-term treatment,
      follow-up and research.

PMID- 30290469
TI  - Advances in medical treatment of Cushing's disease.
AB  - It is well known that transphenoidal surgery is the first line of treatment for
      Cushing's disease (CD). In case of recurrence, pituitary irradiation or
      adrenalectomy are usually performed; however, the morbidity due to these
      procedures is not negligible. For this reason, there is still a strong need for
      medical therapy, although there are only a few controlled data on this field. A
      variety of compounds are invaluable complementary tools in the management of this
      serious condition for which no treatment has yet been proven fully satisfactory.
      Pharmacological treatment could be employed by using neuromodulatory drugs (i.e.,
      serotonin antagonists, dopamine, and GABA agonists) active only in a few cases of
      hypothalamic-pituitary-dependent CD. New approaches at the pituitary tumor level
      involve the potential use of other compounds (e.g., PPAR-gamma agonists and
      retinoic acid). Exciting news in treating CD includes the recent availability of
      new multiligand somatostatin analogues. This review focuses on the new potential
      pharmacologic approaches for the management of CD based on the recent
      identification of possible targets and/or pathogenetic mechanisms.

PMID- 30290470
TI  - Screening and diagnosis of primary aldosteronism.
AB  - Primary aldosteronism (PA) is the most common cause of mineralocorticoid
      hypertension. Different studies using the plasma aldosterone concentration (PAC)
      plasma renin activity ratio (ARR ratio) for the screening of patients with
      hypertension, have shown a marked increase in the detection rate of PA. PA is
      commonly caused by an adrenal adenoma (APA) or idiopathic bilateral adrenal
      hyperplasia of the adrenal zona glomerulosa (IHA) and, in rare cases, by the
      inherited condition of glucocorticoid-remediable aldosteronism (GRA). The early
      diagnosis of PA is important, not only because the forms caused by adrenal
      adenoma are surgically curable, but also because correlation between the duration
      of PA and the development of cardiovascular complications has been reported.
      Patients with resistant and/or severe hypertension, patients with hypokalemia,
      those with a family history of hypertension and stroke at an early age, or
      patients with an adrenal incidentaloma should be screened for PA using the ARR
      ratio. Suspicion of PA owing to a pathological ratio requires confirmatory
      testing, including fludrocortisone suppression test, saline infusion and
      captopril challenge. Adrenal gland imaging is important in subtype
      differentiation (APA vs IHA), but adrenal venous sampling is the gold standard
      and should be used when other tests prove inconclusive. Genetic testing has
      facilitated detection of GRA.

PMID- 30290471
TI  - Polycystic ovary syndrome: a focus on anti-Mullerian hormone levels.
AB  - Anti-Mullerian hormone (AMH) is a dimeric glycoprotein exclusively produced by
      the granulosa cells and reflects the size of the growing follicular pool. Serum
      AMH levels seem to correlate with the development of preantral and small-antral
      follicles during reproductive life. It has been established that AMH levels are
      two- to threefold higher in adult women with polycystic ovary syndrome (PCOS)
      compared with healthy women. This may be related to an increased number of
      growing follicles that secrete AMH or to an increased per granulosa cell
      production. Therefore, the understanding of its regulation is important to
      advance the comprehension of PCOS pathophysiology. Apparently, androgens may play
      an important role in this regard. Recently, our group documented higher serum
      levels of AMH in daughters of women with PCOS compared with control girls during
      three stages of sexual development, early infancy, childhood and peripuberty,
      suggesting the presence of an increased growing follicular pool in these girls
      that is established early in development and precedes the onset of clinical
      hyperandrogenism. In addition, clinical and experimental studies suggest that
      androgens could also have a role in determining an increased follicular mass
      during prenatal life, which, during postnatal life, may perpetuate
      hyperandrogenism. Currently, AMH determination is being progressively used in
      clinical practice as a marker of ovarian function. In the future, it may become a
      useful tool to assess ovarian aging and reserve, to diagnose PCOS and to evaluate
      treatment success.

PMID- 30290472
TI  - Characteristics of familial isolated pituitary adenomas.
AB  - The familial occurrence of pituitary adenomas has been recognized for many years
      and currently accounts for approximately 5% of all cases. Molecular, genetic and
      clinical features of familial pituitary adenomas have been well characterized in
      multiple endocrine neoplasia type 1 (MEN-1) and Carney's complex (CNC), which
      account for the majority of familial pituitary tumor cases. These conditions are
      caused by MEN1 and PRKAR1A gene mutations, respectively, and the clinical and
      pathological features of pituitary pathology in these diseases differ from those
      of sporadic pituitary tumors. Familial acromegaly has been recognized for many
      years and, more recently, the clinical features of this clinical phenotype,
      referred to as isolated familial somatotropinoma, have been clarified. Over the
      past decade, the concept of non-MEN-1/CNC familial pituitary tumors has been
      expanded significantly to include all phenotypes, a condition known as familial
      isolated pituitary adenomas (FIPA). In FIPA, tumors can present homogeneously
      (same phenotype) or heterogeneously (different tumor phenotypes) within the same
      family. Compared with sporadic pituitary adenomas, patients with FIPA have a
      younger age at diagnosis and have larger tumors. The clinical features of FIPA
      differ from those of MEN-1 in terms of a higher frequency of somatotropinomas and
      a lower frequency of prolactinomas. The recent discovery of the involvement of
      mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene in
      association with pituitary tumors has provided new information regarding
      potential mechanisms of tumorigenesis in FIPA patients. While very infrequent in
      sporadic pituitary tumors, approximately 15% of FIPA patients have AIP mutations,
      rising to half of patients with familial acromegaly. In this review, we detail
      the clinical features of FIPA and discuss tumor pathology and genetic findings in
      this increasingly recognized clinical condition.

PMID- 30290473
TI  - Defective functional beta-cell mass and Type 2 diabetes in the Goto-Kakizaki rat
      model.
AB  - Increasing evidence indicates that decreased functional beta-cell mass is the
      hallmark of Type 2 diabetes mellitus. Therefore, the debate focuses on the
      possible mechanisms responsible for abnormal islet microenvironment, decreased
      beta-cell number, impaired beta-cell function and their multifactorial
      etiologies. The information available on the Goto-Kakizaki/Par rat line, one of
      the best characterized animal models of spontaneous Type 2 diabetes mellitus, are
      reviewed in such a perspective. We propose that the defective beta-cell mass and
      function in the Goto-Kakizaki/Par model reflect the complex interactions of
      multiple pathogenic players, including several independent loci containing genes
      responsible for some diabetic traits (but not decreased beta-cell mass),
      gestational metabolic impairment inducing an epigenetic programming of the
      pancreas (decreased beta-cell neogenesis), which is transmitted to the next
      generation, and loss of beta-cell differentiation due to chronic exposure to
      hyperglycemia, inflammatory mediators, oxidative stress and perturbed islet
      microarchitecture.

PMID- 30290474
TI  - International Society of Psychoneuroendocrinology Conference 2007.

PMID- 30290475
TI  - Role of nuclear receptor coregulators in metabolism.
AB  - Understanding the molecular regulation of metabolism will lead to a better
      understanding of the pathogenesis and treatment of common metabolic conditions,
      including obesity and diabetes. Nuclear receptors are a family of transcription
      factors, many of which play major roles in regulating metabolic genes in key
      tissues. They function by recruiting coregulators to the promoters of metabolic
      genes that can either activate or repress transcription. This review examines the
      roles of these coregulators in the control of metabolism in adipose tissue and
      skeletal muscle, and discusses how they result in coordinated and regulated
      control of metabolic pathways. In particular, the ligand-dependent recruitment of
      both coactivators and corepressors has potential implications for the treatment
      of obesity and diabetes.

PMID- 30290476
TI  - Systemic and endocrine manifestations of Langerhans' cell histiocytosis: current
      concepts in diagnosis and management.
AB  - Langerhans' cell histiocytosis (LCH) is a rare disease of unknown etiology and
      variable biologic behavior and course. Almost every organ can be affected;
      however, it frequently involves the bones, lungs, skin and lymph nodes. LCH
      exhibits a particular predilection for involvement of the hypothalamo-pituitary
      axis resulting in diabetes insipidus and/or other anterior pituitary
      deficiencies. Although LCH can sometimes resolve spontaneously, it usually
      follows a chronic course and systemic treatment is mandatory for the management
      of multisystem disease. However, a significant number of patients will develop at
      least one permanent sequela as a consequence of the disease, with diabetes
      insipidus being the most common. A multidisciplinary approach is always needed in
      diagnosis, treatment and follow-up of all patients with LCH.

PMID- 30290477
TI  - The future of forensic mental health services in Ireland.

PMID- 30290478
TI  - Psychiatric morbidity among women prisoners newly committed and amongst remanded
      and sentenced women in the Irish prison system.
AB  - OBJECTIVES: To estimate the prevalence of psychiatric morbidity, substance misuse
      problems and related health and social problems among women prisoners newly
      committed and a cross-section remanded and sentenced in the Irish prison
      population. In 2002 women represented 10.7% (1043) of all persons committed to
      the Irish Prison system, and 3.3% (104) of the daily average number of persons in
      custody. We surveyed psychiatric morbidity in these two groups to assess the need
      for psychiatric services for women prisoners, and to compare Irish morbidity with
      an international average. METHOD: We interviewed 94 newly committed women
      prisoners within 72 hours of committal, representing approximately 9% of female
      committals per year. We also interviewed a cross sectional sample of 92 women,
      representing approximately 90% of all women in custody. Mental illness and
      substance misuse was measured using the SADS-L, SODQ and a structured interview.
      RESULTS: Five (5.4%) of the committal and 5 (5.4%) of the cross-sectional sample
      had a psychotic illness within the previous six months. 8 (8.5%) of the
      committals and 15 (16.3%) of the women in the cross-sectional sample had a major
      depressive disorder in the last six months. 8 (8.6%) committals and 14 (15.2%) in
      the cross-sectional sample had an anxiety disorder within the last six months. 61
      (65.6%) of the women interviewed at committal and 61 (65.2%) of the cross
      sectional sample had a substance misuse problem in the last six months.
      CONCLUSIONS: There is a high prevalence of mental illness and substance misuse
      problems amongst women newly committed to prison and in a cross section of those
      remanded or sentenced in prison in Ireland. We found evidence of a cycle of
      deprivation and institutionalisation. These findings highlight the need for the
      integration of community and forensic psychiatric services, and for ongoing
      collaboration with drug services.

PMID- 30290479
TI  - Psychiatric morbidity in the male sentenced Irish prisons population.
AB  - BACKGROUND: This is the first epidemiologically representative cross-sectional
      study of psychiatric morbidity using research diagnostic instruments in sentenced
      prisoners in Ireland. OBJECTIVE: To estimate the prevalence of psychiatric
      morbidity and psychiatric service requirements. METHOD: We interviewed 340 men
      serving a fixed sentence (14.6% of total) and 98 men serving a life sentence (82%
      of total). Prisoners were drawn from 15 different prisons using a random
      stratified sampling method. Mental illness and substance misuse was measured
      using the SADS-L, SODQ and a structured interview to generate ICD-10-DCR
      diagnoses. RESULTS: We found a high prevalence of mental illness. Our six month
      prevalence for psychosis (2.7%) was similar to an international meta-analysis. We
      found a significantly higher prevalence of psychosis in life sentenced prisoners
      (6.1%) compared to fixed sentenced prisoners (1.8%). Drugs and alcohol problems
      were very prevalent. CONCLUSIONS: Using the six month prevalence figures found
      for psychosis, we estimate that there are approximately 79 sentenced male
      prisoners with a severe mental illness who would require treatment in hospital
      additional to current provision. We discuss the relationship between drug
      availability and the prevalence of severe mental illnesses in prisons.

PMID- 30290480
TI  - Drug treatment programmes in prison: longitudinal outcome evaluation, policy
      development and planning interventions.
AB  - AIMS: The aim of this research is to evaluate a seven week abstinence-based drug
      treatment programme and to use this to assist policy makers in the planning and
      provision of future programmes. METHODS: Design: Seventy-nine clients were
      interviewed at two stages. Stage I, prior to the treatment programme, stage II,
      immediately after the treatment programme. A selected group of 20 clients were
      followed-up and interviewed at stage III, up to 24 months after the treatment
      programme. SETTING: All clients were prisoners at Mountjoy Prison, Dublin
      Ireland. PARTICIPANTS: Seventy-nine male prisoners were recruited. A sample of 20
      of the original cohort of 79 was selected using a snowball sampling method
      approximately 24 months following treatment. This latter sample of 20 clients
      consisted of eight prisoners who had re-offended and returned to prison, three
      prisoners who were still in prison serving their original sentence and nine
      prisoners who were out of prison. These 20 also participated in a more detailed
      quantitative and qualitative survey. MEASUREMENTS: In order to measure prisoner's
      criminogenic attitudes and needs the Crime Pics II instrument was used. This is a
      semantic differential scale which measures attitudes toward offending behaviour.
      It includes a problem checklist which can be used to measure change over time.
      RESULTS: An 82% follow-up rate was achieved on the original group of 79 clients,
      similarly a follow-up rate of 100% was also achieved for the selected group of 20
      clients who were interviewed three times. Regardless of category of client,
      findings demonstrate an improvement over time for the outcome variables, general
      attitude to offending, anticipation of re-offending and perception of current
      life problems. However, the study failed to demonstrate any significant change
      for the outcome variables victim hurt denial and evaluation of crime as
      worthwhile. CONCLUSIONS: These results were short lived for many prisoners, who
      failed to sustain the gains made. Interviews with the cohort of 20 who underwent
      stage III interviews possibly suggest that those clients who did not receive
      continuity of treatment post programme, in terms of case management and
      structured treatment did not fare as well as those who did.

PMID- 30290481
TI  - Variations in residential accommodation for adults with intellectual
      disabilities: the example of Northern Ireland.
AB  - OBJECTIVES: Over the past three decades, major changes have taken place
      internationally in the type of residential accommodation provided for people with
      intellectual disabilities but these appear to be less evident in Northern
      Ireland. METHOD: A census was undertaken of all persons in any form of
      residential placement using a range of existing databases to identify the
      population, with a short questionnaire completed for each resident. RESULTS:
      Around 440 persons lived in hospitals and 1,970 in some other form of provision
      but mostly in large congregated settings such as residential care homes and
      nursing homes. This was more marked in certain Health and Social Service Boards
      than in others. Most places are provided by the private sector although voluntary
      organisations and housing associations now manage around one-third of places.
      People living in hospitals reportedly had different characteristics to those in
      all other settings while those in nursing homes tended to require greater
      personal care. However the characteristics of people living in residential homes,
      supported living arrangements and village communities were broadly comparable.
      Around one in 10 persons were deemed to benefit from a move; mostly from
      residential homes to more independent living arrangements. CONCLUSIONS: Compared
      to Britain and the Republic of Ireland there is an under-provision of residential
      placements in Northern Ireland. To date, funding from outside of health and
      social services has been the main driver for the type of accommodation provided.
      The implications for future policy and provision are discussed.

PMID- 30290482
TI  - Psychiatry in contemporary Irish cinema: a qualitative study.
AB  - OBJECTIVE: Media portrayals of mental illness and psychiatry have a considerable
      impact on public perceptions of mental health issues. This paper aims to focus on
      portrayals of psychiatry and psychiatrists in four contemporary Irish feature
      films in order to make wider points on this theme. METHODS: Contemporary Irish
      feature-films that made substantial reference to psychiatry, psychiatrists or
      mental health in Ireland were identified though electronic searches and
      consultation with the Film Institute of Ireland. Selected films were viewed.
      Electronic searches were performed in the medical and film literatures, with
      broad search terms related to film, psychiatry, psychiatrists or mental health in
      Ireland. Additional books and papers were identified by tracking back through
      references and consulting with colleagues. RESULTS: The portrayal of
      psychiatrists in film is closely related to the development of both twentieth
      century psychiatry and twentieth century cinema. In common with recent European
      films, certain recent Irish films have tended to show psychiatrists as
      sympathetic, humane individuals (with some notable exceptions). While there have
      been a number of portrayals of dissocial personally disorder and various states
      of chronic alienation in recent Irish film, there have been fewer portrayals of
      psychosis or learning disability. Recent Irish films emphasise the role of
      alcohol in causing and perpetuating psychological distress. They generally
      provide unflinching portrayals of the effects of psychological distress and
      alienation, suicide and substance abuse at individual, family and community
      levels; nonetheless, there is still a regrettable tendency for films to associate
      mental illness with dissocial behaviour. CONCLUSIONS: The portrayal of mental
      health issues in film presents both challenges and opportunities to film-makers,
      mental health service-users and general audiences alike. It is to be hoped that
      the recent trend towards realistic explorations of mental health issues in many
      European films continues into the future. Increased research in this area would
      help clarify the role of cinema in shaping public understandings of mental
      illness, and may also help identify additional ways of addressing stigma in the
      future.

PMID- 30290484
TI  - Telepsychiatry: A solution to clinical efficacy or cost effectiveness.

PMID- 30290483
TI  - Attitudes towards the implementation of the Mental Health Act 2001.

PMID- 30290485
TI  - Correction.

PMID- 30290486
TI  - Neuroimaging in psychiatry.

PMID- 30290487
TI  - A needs analysis for the provision of a speech and language therapy service to
      adults with mental health disorders.
AB  - OBJECTIVES: To examine a sample of adults with mental health disorders attending
      at an area psychiatric service, for the presence of impairments in language,
      communication and swallowing, using a test battery administered by speech and
      language therapists. METHOD: The study surveyed a randomly selected sample (n =
      60) of patients from an acute psychiatric inpatient unit and associated community
      services, using several standardised measures of language, communication and
      swallowing. RESULTS: On this test battery, over 80% (50/60) of subjects studied
      demonstrated impairment in language; while over 60% (37/60) presented with
      impairment in communication and discourse. Over 30% (18/58) of subjects assessed
      showed some impairment in swallowing. CONCLUSION: Use of this test battery
      confirmed the presence of language, communication and swallowing impairments in
      many patients in this sample of attenders at a general psychiatry service. We
      suggest that this study provides evidence for a (currently unmet) need for
      specialist speech and language therapy assessment and support among this patient
      population.

PMID- 30290488
TI  - Information sharing and risk: a survey of psychiatrists.
AB  - OBJECTIVES: Historical information is central to decision making in mental health
      care. Clinical information in the Irish mental health services is currently
      mostly paper based. Mental health care in Ireland has moved from an institutional
      medical model towards a community based multidisciplinary model in recent years.
      This change has resulted in a dispersal of information between multiple sites and
      professionals, rendering it less accessible, particularly in emergency settings.
      This study sought to find out if psychiatrists working in Ireland were
      experiencing information problems, their ideas about and attitudes towards
      electronic solutions to these problems, and their views as to what particular
      pieces of information are indispensable in emergency mental health assessments.
      METHOD: A questionnaire was designed to answer these questions and sent to a
      representative sample of 150 psychiatrists working in Ireland. RESULTS: One
      hundred and nineteen questionnaires (79.3%) were returned complete. Of the 119
      respondents 98(82.4%) stated that they had performed emergency mental health
      assessments within the past year without access to key information and 79(66.4%)
      said they would have made different decisions in some cases had they had all the
      available information. Information deficits were particularly apparent in liaison
      and forensic psychiatry. Of the respondents 110(92.4%) stated that they would
      welcome an electronic database designed to support emergency mental health
      assessments. Misgivings were expressed regarding forms of consent, data quality,
      breach of confidentiality, resources and much more. Risk factors (ie. self-harm
      potential), a high alert message and medication details were the data items
      thought to be most critical. CONCLUSIONS: A shareable set of essential pieces of
      information (a minimum data set) would offer a balance between patient safety,
      confidentiality and shareability. A wider debate about solutions to the
      information deficits in mental health care in Ireland needs to take place among
      all stakeholders so that this idea can be moved forward.

PMID- 30290489
TI  - Electroconvulsive therapy: International guidelines, clinical governance and
      patient selection.
AB  - Recent reports from the Inspector of Mental Health Services have highlighted
      marked variations in electroconvulsive therapy (ECT) prescriptions nationally.
      This article reviews six international guidelines in order to assess the question
      of which patients should be referred for ECT treatment and at what stage in their
      illness. The guidelines display a general consensus in terms of the acutely and
      severely ill, but differ dramatically in terms of access to ECT outside this
      category, such as the moderately depressed patient who is treatment resistant but
      non-psychotic and non-suicidal and who requests ECT due to a previous good
      response. The American Psychiatric Association guidelines strongly support the
      early consideration and use of ECT, highlighting the dangers associated with
      increased length of illness for individual prognosis. The National Institute of
      Clinical Excellence (UK) guidelines are the strictest, reserving ECT for the
      severely ill exclusively and only in cases with a demonstrable failure of
      alternative treatments. This confusion may ultimately need to be addressed by the
      Mental Health Commission as data relating to variations in practice may result in
      inappropriate reductions in access to an established treatment.

PMID- 30290490
TI  - One hundred years ago: The Richmond Asylum, Dublin in 1907.
AB  - The Richmond Asylum (St Brendan's Hospital) in Grangegorman, Dublin was
      established in 1815 to help address the unmet needs of the mentally ill in 19th
      century Ireland. This paper examines the Richmond Asylum Joint Committee Minutes
      from 1907 in order to explore specific aspects of management and clinical
      activity at the Richmond Asylum, including: (a) patient populations in the
      asylums; (b) staffing and management issues; (c) challenges presented by
      workhouse populations in the early 20th century; and (d) the clinical
      'segregation' of patients performed by the Medical Superintendent, Dr Conolly
      Norman, in 1907.

PMID- 30290491
TI  - Disulfiram induced peripheral neuropathy: between the devil and the deep blue
      sea.
AB  - Disulfiram is widely used for the aversive treatment of alcoholism. It is well
      tolerated in most patients; however 1:15,000 will develop peripheral neuropathy,
      which is frequently misdiagnosed as alcoholic neuropathy. Most cases present with
      a motor-sensory neuropathy of the lower limbs, which tends to improve when
      administration ceases, though some cases may be left with permanent sequelae.
      This adverse reaction can be avoided by using the lowest effective dose. A
      literature review using the Medline revealed 66 citations relating disulfiram to
      peripheral neuropathy, and the number of cases reported is small.

PMID- 30290492
TI  - Influence of ethnicity on presentation and outcome of first episode psychosis.
AB  - We describe a young African male presenting to an Irish psychiatric service with
      first episode psychosis with an acute onset, no prodromal features and early and
      complete remission. Migrant and ethnic minority groups may differ in their
      clinical presentation, course and outcome of psychosis compared with the
      Caucasian population. This has implications for assessment and treatment of
      ethnic minority patients in an Irish context given the recent migration into a
      previously homogeneous population.

PMID- 30290493
TI  - Impact of Ramadan on the treatment of psychosis.
AB  - A 35-year-old South Asian Muslim male was admitted for acute psychotic episode to
      an urban acute psychiatric unit. In the context of ongoing religious delusions,
      and on his request to fast during the Islamic month of Ramadan we made
      alterations to his medication dosing schedule. We discuss the clinical
      implications of such practice.

PMID- 30290494
TI  - Clozapine induced stuttering.
AB  - We describe two cases reports, demonstrating an association between clozapine
      treatment and stuttering. Stuttering in both cases was dose-related and a
      significant improvement was noted when the dose of clozapine was reduced.

PMID- 30290495
TI  - Follow up of people recently discharged from psychiatric inpatient care.

PMID- 30290496
TI  - Social justice, human rights and mental illness.

PMID- 30290497
TI  - Group cognitive behavioural therapy for children with anxiety disorder - an
      evaluation of the 'Friends for Youth' programme.
AB  - OBJECTIVES: This study evaluated the effectiveness of group cognitive behavioural
      therapy (GCBT) for the treatment of anxiety disorders in children over an initial
      period of 12 weeks and to one-month follow-up. Parents of the children receiving
      GCBT participated in adjunctive psycho-education sessions and the effect of these
      sessions on parental anxiety was also evaluated. METHODS: Participants were 12
      children, six male and six female, aged between 11 and 15 years who were
      attending a child mental health service. Participants were interviewed with their
      parents and anxiety symptoms assessed, using the following measures: Anxiety
      Disorder Interview Schedule - revised, the Children's Depression Inventory, the
      Revised Children's Manifest Anxiety Scale, the Coopersmith Self-Esteem Inventory
      and the Child Behaviour Checklist. Parental anxiety levels were assessed using
      the Depression, Anxiety and Stress Scale. The 12 children were randomly assigned
      into two age- and sex-matched groups. While the first group received therapy, the
      second group acted as a treatment-as-usual control (TAU) group. The second group
      began group cognitive behavioural therapy after the 10-week waiting period. All
      participants and their parents provided structured feedback on the intervention.
      RESULTS: Group cognitive behavioural therapy was significantly effective in
      reducing both child-reported depressive symptoms, and anxiety on the
      physiological, worry and total anxiety subscales of the Revised Children's
      Manifest Anxiety Scale. There were associated significant increases in the
      childrens' subjective levels of general and total self-esteem, that relating to
      their self-confidence with peers and when engaging in social and academic
      pursuits. Diagnosis of anxiety disorder reduced by an average of 67% immediately
      post-treatment, and by 72% by the onemonth follow-up period. Parents reported
      significant reductions in their children's levels of internalising symptoms,
      thought and attention problems. However, parents reported no significantly
      positive changes in their own levels of depression, anxiety and stress symptoms.
      CONCLUSIONS: Group cognitive-behavioural therapy is a useful and clinically
      effective intervention for the treatment of anxiety disorder in children.

PMID- 30290498
TI  - The validity of a latent class typology of adolescent drinking patterns.
AB  - OBJECTIVES: This study examined the validity of a latent class typology of
      adolescent drinking based on four alcohol dimensions; frequency of drinking,
      quantity consumed, frequency of binge drinking and the number of alcohol related
      problems encountered. METHOD: Data used were from the 1970 British Cohort Study
      16-year-old follow-up. Partial or complete responses to the selected alcohol
      measures were provided by 6,516 cohort members. The data were collected via a
      series of postal questionnaires. RESULTS: A five class LCA typology was
      constructed. Around 12% of the sample were classified as 'hazardous drinkers'
      reporting frequent drinking, high levels of alcohol consumed, frequent binge
      drinking and multiple alcohol related problems. Multinomial logistic regression,
      with multiple imputation for missing data, was used to assess the covariates of
      adolescent drinking patterns. Hazardous drinking was associated with being white,
      being male, having heavy drinking parents (in particular fathers), smoking,
      illicit drug use, and minor and violent offending behaviour. Non-significant
      associations were found between drinking patterns and general mental health and
      attention deficient disorder. CONCLUSION: The latent class typology exhibited
      concurrent validity in terms of its ability to distinguish respondents across a
      number of alcohol and non-alcohol indicators. Notwithstanding a number of
      limitations, latent class analysis offers an alternative data reduction method
      for the construction of drinking typologies that addresses known weaknesses
      inherent in more tradition classification methods.

PMID- 30290499
TI  - Alcohol dependence and mood state in a population receiving methadone maintenance
      treatment.
AB  - OBJECTIVES: The aim of this study was to assess the prevalence of alcohol
      dependence and anxiety and depressive disorder symptomatology among heroin users
      in drug treatment. METHOD: Fifty-five clients on methadone maintenance treatment
      programmes in Dublin were interviewed. RESULTS: Prevalence rates were found to be
      56% [n = 31] for alcohol dependence, 56% [n = 31] for anxiety disorder
      symptomatology, and 42% [n = 23] for depressive disorder symptomatology. This
      finding of comorbid alcohol dependence and psychopathology among methadone
      maintenance treatment clients suggests that both clients' health and methadone
      maintenance treatment participation and completion rates may be compromised.
      CONCLUSIONS: Alcohol dependence and psychopathology among methadone maintenance
      treatment clients should be considered when providing effectively targeted
      services to the drug using population.

PMID- 30290500
TI  - Effectiveness of daily outpatient alcohol detoxification by an Irish public
      psychiatric hospital - A pilot study.
AB  - OBJECTIVE: To assess the effectiveness of daily outpatient alcohol detoxification
      in an Irish public psychiatric hospital. METHOD: The outpatient records of
      patients presenting to the Assessment Unit of St Brendan's Hospital in one year
      (August 2004-July 2005) with symptoms of Alcohol Dependence Syndrome (ADS) and
      commencing daily outpatient detoxification were examined retrospectively for
      parameters relevant to the objectives of the study. The results were compiled and
      analysed using descriptive statistics. RESULTS: Forty patients underwent
      outpatient alcohol detoxification in one year and complete records were available
      for 32 patients (80%). Twenty patients had fixed addresses in the hospital
      catchment areas, eight patients had no fixed addresses and the remaining four
      patients had addresses outside the catchment areas. Seven patients (22%)
      presented with a co-morbid psychiatric condition including depression (four
      patients), anxiety disorder (two patients) and personality disorder (one
      patient). All seven patients were known to psychiatric sector services. Of the 32
      patients commencing detoxification, 28 patients (87.5%) attended on the second
      day whilst 22 patients (69%) attended their third day's appointment. Only 17
      patients (53%) completed the outpatient detoxification. Thirteen patients (40.6%)
      received at least two outpatient detoxifications during the year; of whom seven
      patients (58%) received their second detoxification within two months of the
      first one. The record of 20 patients (62.5%) showed that they had received advice
      regarding selfreferral to counselling services. CONCLUSION: A high proportion of
      patients (47%) presenting with symptoms of ADS did not complete daily outpatient
      detoxifications. A high proportion of all patients (40.6%) also underwent
      multiple outpatient detoxifications during the year. It is possible that the
      separation between alcohol detoxification and alcohol counselling services in
      Ireland contributed to these disappointing results.

PMID- 30290501
TI  - Does psychoeducation influence carers' attitudes to treatment of schizophrenia?
AB  - OBJECTIVE: To measure the impact of a six-week Carer Psychoeducation Program
      (CPP) on factors that influence attitudes towards treatment among carers and
      relatives of people suffering from schizophrenia. We also examined which specific
      attitudes to treatment the CPP had the most effect on. METHOD: Between 2002 and
      2004, all patients and their relatives continued standard care. During this
      period, we conducted a historically-controlled open trial, in which 64 relatives
      completed a 17-item adapted version of the Drug Attitudes Inventory (DAI) before
      and after the CPP. RESULTS: Attitudes to treatment improved significantly overall
      (p < 0.001), an improvement most marked in terms of attitudes to health and
      illness, attitudes towards the physician and attitudes towards the potentially
      harmful effects of treatment. No statistically significant improvement was found,
      however, in attitudes to locus of control or the preventative role of treatment.
      CONCLUSION: A CPP specifically improves family attitudes towards treatment. This
      finding is clinically important because such attitudes influence adherence which,
      in turn, influences outcome. The fact that certain attitudes are influenced by
      the CPP, while others are not, may help to explain the mechanism through which
      patient outcomes improve.

PMID- 30290502
TI  - International human rights law and mental illness.
AB  - The Irish State has been party to a collection of international treaties and
      declarations that directly affect the care of those who suffer from mental
      disorders. These documents set up what are considered as minimum core standards
      that outline the standard of care that should be provided as a basic human right.
      This article reviews the relevant sections of these documents and reflects as to
      how they have been applied in Ireland. International conventions, which have the
      status of a treaty, are monitored and interpreted by various commissions and
      committees. This article draws on the comments of these bodies as to how a state
      should provide for those with mental illness. Areas such as the rights of
      children who are mentally ill and those who are detained by the state are
      examined in detail. Other areas covered are the right to the highest attainable
      level of mental health care, the right not to be subjected to a clinical trial,
      equal access to mental health care, and the right to be safeguarded against
      unjust involuntary detention.

PMID- 30290503
TI  - Borderline personality disorder and clozapine.
AB  - Clozapine is an atypical anti-psychotic medication that has proved useful in the
      management of both psychotic and mood disorders and that has been shown to
      decrease aggression and the risk of suicide, which suggests that clozapine may be
      useful in the management of severe borderline personality disorder. Here we
      present the case of a 36 year old female with severe borderline personality
      disorder with symptoms of psychosis, aggression and violence. We discuss how
      treatment with clozapine resulted in a marked clinical improvement in this
      patient.

PMID- 30290504
TI  - Antidepressant discontinuation and hypomania.

PMID- 30290505
TI  - Discontinuation syndrome en masse.

PMID- 30290506
TI  - Liaison between criminal justice and psychiatric systems: Diversion services.

PMID- 30290507
TI  - Violence and aggression in the Drug Treatment Centre Board.
AB  - OBJECTIVES: We sought to determine the prevalence of and the factors associated
      with violent and aggressive incidents among clients attending an out-patient
      methadone stabilisation and detoxification programme in Dublin. METHODS: We
      retrospectively examined all incident report forms over a two-year period. We
      also obtained information on demographics, main drug of abuse, timing and
      location of the incident as well as psychiatric and physical comorbidity among
      the perpetrators from case note review. RESULTS: Two hundred and ninety-five
      incidents occurred over the study period. The overall rate of violence and
      aggression was 85 per 1,000 clients attending the centre per year. Most incidents
      involved verbal abuse. Females were significantly more likely to be involved in
      assaults compared to males. A high proportion of clients (80%) who were
      physically aggressive tested positive for benzodiazepine medication. CONCLUSIONS:
      Levels of recorded violence have remained stable however racial abuse has
      increased in recent years. The relatively low overall rate of violence suggests
      that existing measures have helped reduce the number of aggressive and violent
      incidents in the centre. Most of the victims were either doctors, nursing staff
      or general assistants. This finding reflected their respective roles in the
      centre, which included limit setting and dealing with positive drug screens among
      clients.

PMID- 30290508
TI  - The assessment of need in patients presenting to psychiatrists in the general
      hospital.
AB  - OBJECTIVE: The evaluation of psychosocial need is an important part of the
      assessment of any patient who presents to a psychiatrist. The Camberwell
      Assessment of Need (CAN) instrument was developed for the systematic assessment
      of need in people with severe and enduring mental illness. Variations of the CAN
      have been developed for forensic, elderly and learning disability populations.
      Patients presenting to psychiatrists in the general hospital may also have
      different needs to those presenting to psychiatrists in other settings. We set
      out to examine whether the CAN would be useful in identifying needs in patients
      referred to psychiatrists in the general hospital with self-harm or alcohol
      problems. METHOD: Over a four-month period from September 2004 we prospectively
      assessed all patients with self-harm or alcohol problems referred to a liaison
      psychiatry service. We used the short version of the Camberwell Assessment of
      Need instrument (CANSAS) to assess psychosocial needs. Urgent referrals to a
      local psychiatric service of patients with severe enduring mental illness (SEMI)
      were assessed using identical methodology over the same time period and used as a
      comparison group. RESULTS: Over the study period 53 patients with self-harm, 42
      with alcohol problems and 45 with SEMI were assessed. Patients presenting with
      self-harm and alcohol problems had significantly fewer needs than those with SEMI
      (4.40 vs 3.98 vs 7.96, p < 0.001). Looking after the home, self-care, daytime
      activity, psychotic symptoms, safety to others and sexual expression needs were
      significantly greater in the SEMI group than in either the DSH or alcohol groups.
      Only safety to self-needs in the DSH group and alcohol needs in the alcohol group
      were significantly higher than in the SEMI group. The proportion of needs that
      were unmet was similar in each group. CONCLUSIONS: The CANSAS instrument
      identified some needs in deliberate self-harm and alcohol problem patients that
      might not have been identified during the course of a standard psychosocial
      assessment. It was easy to administer and as such was a useful addition to the
      assessment process. However the development of a more specific instrument for the
      assessment of need in these populations would be useful.

PMID- 30290509
TI  - Detection, assessment and management of eating disorders; how involved are GPs?
AB  - OBJECTIVES: To determine the extent to which general practitioners are currently
      active in the screening, assessment, diagnosis and management of eating
      disorders. To identify current deficits in service delivery for eating disordered
      patients, as identified by general practitioners. METHOD: A postal questionnaire
      was circulated to 360 general practitioners within the greater Dublin area and
      North Eastern Health Service Executive. RESULTS: Response rate was 25%.
      Respondents had lower case-loads of eating disordered patients than would be
      expected given the epidemiology of anorexia and bulimia nervosa. Most do not
      routinely screen for eating disorders, even in at-risk populations and are
      unaware of the current evidence-based data for guidance. GPs do not feel
      confident at managing eating disorders within the primary care setting and see
      their chief role as that of referral to psychiatric services. Treatment outcomes
      are typically poor. Concern was expressed at the lack of access to specialist
      treatment in the public sector. Specific deficits in service provision were
      highlighted including delays in assessment, lack of services appropriate to the
      adolescent population, poor service transition, and poor availability of
      psychotherapy at primary care level. CONCLUSIONS: Eating disorders are currently
      underdiagnosed in the primary care setting. Use of simple screening tools might
      aid detection of pathological eating patterns, particularly in at-risk groups.
      General practitioners feel under-equipped to manage these complex disorders,
      given that the resources required to provide high quality care are not widely
      available. Better integration of primary and secondary services, coupled with
      training for GPs in the area of screening, assessment and diagnosis, may lead to
      earlier intervention and improved outcomes.

PMID- 30290510
TI  - Atypical antipsychotic monitoring: A survey of patient knowledge and experience.
AB  - OBJECTIVES: To examine the knowledge and experiences of side-effects and their
      monitoring in patients prescribed atypical antipsychotic medications. METHODS: A
      tick box survey was designed to ask questions of patients prescribed atypical
      antipsychotic medications about side-effects and monitoring for them. This survey
      was distributed anonymously to all suitable outpatient attendees over a three
      month period who had been prescribed atypical antipsychotic medication for at
      least one year. RESULTS: Seventy-four of the 90 surveys (82%) distributed were
      returned complete. Fifty-six (76%) of those surveyed said they were currently
      experiencing side-effects. Twenty-two (39%) said they had not told their
      psychiatrist about the side-effects. Weight gain was most commonly complained of
      (49%). Forty-five (61%) said that they had had no monitoring blood tests in the
      past year. Fifty-one (69%) did not know that certain monitoring blood tests were
      recommended. CONCLUSIONS: Patients prescribed atypical antipsychotic medications
      are not currently being monitored as best practice dictates. It cannot be assumed
      that GPs will pursue this monitoring. More resources are needed for mental health
      services so that adequate monitoring services can be provided.

PMID- 30290511
TI  - Tackling a long waiting list in a child and adolescent mental health service.
AB  - OBJECTIVE: Long waiting lists have a negative impact on client satisfaction,
      staff moral and referrer's opinion of the service. The aim of this project was to
      decrease a waiting list from a maximum wait of more than one year to a wait of no
      more than six weeks. METHOD: We introduced three simultaneous initiatives to
      decrease a long waiting list; (i) an individually led triage system (ii) setting
      up an attention deficit hyperactivity disorder (ADHD) specialist team and (iii)
      division of the residual waiting list between team members. These initiatives
      were introduced and analysed over a ten month period. The study period ran from
      1/3/2004 to 31/12/2004. RESULTS: The waiting time to first appointment was
      significantly reduced. At the beginning of the study there were 62 people waiting
      to be seen and each had waited an average of 122 days with a waiting time range
      of 0-449 days. At the end of the study, there were 19 people waiting with a mean
      waiting time of 19 days and a range of 0-168 days. CONCLUSIONS: The single most
      powerful intervention was the triage system. The ADHD clinic allowed referrals to
      be streamlined in a very structured and efficient way. The division of the
      residual waiting list was not as onerous as it first appeared. The service saw
      more referrals then ever during the study period. Referrers and families
      appreciated being seen more quickly. By removing the burden of the waiting list
      from staff the potential for creative thinking around further development of the
      service increased.

PMID- 30290512
TI  - Survey of a second opinion clinic in child and adolescent psychiatry.
AB  - OBJECTIVES: Second opinion is a medical opinion provided by a second physician/
      medical expert after first receiving an opinion by another physician/ medical
      expert. Little is known about the provision of second opinion in Child and
      Adolescent Mental Health Services (CAMHS). This study describes the second
      opinion service provided by the Child and Adolescent Mental Health Services
      (CAMHS) in the South Wales region. METHODS: We undertook a survey of a second
      opinion service in Child and Adolescent Mental Health Services (CAMHS). We also
      assessed whether the recommendations made by the second opinion clinic were
      implemented by the referrers. RESULTS: The diagnoses were not changed in 68% of
      the cases but alternative treatments were suggested. In 90% of the cases the
      treatment recommended by the clinic was implemented and nearly 70% of the
      patients showed improvement with the recommended treatment. CONCLUSION: A second
      opinion service can provide valuable support and expertise to CAMHS and the
      referred families.

PMID- 30290513
TI  - Read all about it: guided bibliotherapy for depression in adults.
AB  - Early intervention in depression is important for many reasons including
      expeditious alleviation of suffering, assisting parenthood, suicide prevention
      and helping the economy. The fact that people with depression frequently employ
      maladaptive coping strategies, notably alcohol misuse, suggests the need for
      evidence-based self-help for sufferers. Self-help can be viewed as a philosophy
      of patient empowerment and as "a health technology solution to volume and
      demand". Bibliotherapy (self-help using written materials) provides information
      and encourages the reader to make changes leading to improved self-management.
      Enthusiasm for the use of bibliotherapy in depression should be tempered by
      pursuit of a sound evidence base.

PMID- 30290514
TI  - Olanzapine-induced rhabdomyolysis.
AB  - We present a case of possible olanzapine-induced rhabdomyolysis in the absence of
      other features of neuroleptic malignant syndrome (NMS). There is evidence to
      suggest that there are different underlying pathophysiological mechanisms for
      rhabdomyolysis occurring alone, in contrast to when it presents as part of NMS.
      This has possible implications for drug rechallenge which is discussed.

PMID- 30290515
TI  - Duloxetine-mirtazapine combination in depressive illness: The case for Limerick
      'rocket fuel'.
AB  - The use of complex psychopharmacological regimens is increasingly advocated in
      more difficult to treat depressive illness. The combination of venlafaxine with
      mirtazapine - 'California rocket fuel' is one such example involving an SNRI
      combined with a NaSSA. We describe two cases that highlight the potential
      usefulness of duloxetine used in combination with mirtazapine that also emphasise
      the danger of drug-induced hypomanic switching. This combination may have a
      specific role for carefully selected patients but caution is needed given the
      potential to induce profound alterations in mental state.

PMID- 30290517
TI  - Central Mental Hospital Study.

PMID- 30290516
TI  - Drug diversion of Oxycontin in chronic pain syndrome.
AB  - Abstrsct A case is described in which a man with chronic pain syndrome (CPS)
      presented to a city General hospital in suicidal crisis after referral from a
      provincial psychiatric unit, having taken an overdose of a variety of
      medications, precipitated by the absence of his opioid (Oxycontin) analgesia
      which he had been abusing intra-nasally. This is to our knowledge the first
      reported case in Europe of drug diversion from oral to intranasal use of
      Oxycontin, a controlled-release preparation of the synthetic opiate, oxycodone
      hydrochloride. There is also a dearth of reference to the abuse potential of this
      agent in the European literature. As sufferers from chronic pain syndrome
      increase in number, and opiate prescription rates worldwide are maintained, this
      case highlights the potential of opiate abuse or dependence and drug diversion
      emerging as a significant medical problem in CPS patients in Europe.

PMID- 30290518
TI  - The Dissociative Experiences Scale.

PMID- 30290519
TI  - Self-esteem in national school children in Ireland.

PMID- 30290520
TI  - Psychiatric morbidity in prisoners.

PMID- 30290521
TI  - Pimozide treatment for body dysmorphic disorder.

PMID- 30290522
TI  - Persons with acquired brain injury: a disabled diaspora.

PMID- 30290523
TI  - Empowerment, quality of life and service satisfaction: comparisons between a
      hospital and community placement group.
AB  - OBJECTIVES: Recent advances in mental healthcare policy and service delivery have
      lead to the development of community care initiatives which have enabled those
      individuals traditionally cared for in hospital environments to be resettled
      successfully in community living arrangements that foster an ethos of empowerment
      and recovery. This study sought to identify differences between a hospital
      continuing care group (n = 16) and a community placement group (n = 20) in
      relation to quality of life, satisfaction and levels of empowerment. METHOD: The
      study was a cross-sectional design. It follows up a cohort of individuals
      identified as the 'hospital continuing care group' (365+ consecutive days in
      psychiatric hospital care) by Homefirst Community Trust in Northern Ireland. A
      proportion of this population has been resettled into community care environments
      and some continue to reside in hospital. Patients both in the hospital continuing
      care group and the community placement group completed two standard
      questionnaires that covered a number of variables including empowerment, quality
      of life and service satisfaction. RESULTS: There were significant differences
      between the hospital continuing care and community placement groups across scores
      on service satisfaction, quality of life, and empowerment in the current study.
      Hypotheses relating to service satisfaction (z = -4.117; p < 0.01 ), quality of
      life (z = -3.944; p < 0.01) and empowerment (z = -4.645; p < 0.01) were supported
      with higher levels of each evidenced by the community placement group.
      CONCLUSIONS: The results are supportive of continued resettlement from continuing
      care in traditional psychiatric hospitals and suggests that such resettlement
      increases quality of life, satisfaction with services and levels of empowerment.
      The limitations of the research design are empowerment. The limitations of the
      research design are also discussed.

PMID- 30290524
TI  - Opiate-dependent adolescents in Ireland: a descriptive study at treatment entry.
AB  - OBJECTIVES: To describe the drug history and co-existing psycho-social problems
      among under-19 year olds accessing treatment for opiate dependency, including
      methadone maintenance, and examine for any gender differences. METHOD: A
      descriptive study of under-19 years assessed at the largest drug treatment clinic
      in Dublin, Ireland, between October 2000 and September 2006. Data was obtained
      through review of case notes, assessment questionnaires and urine drug screens.
      RESULTS: Eighty-six young people were included. Their mean age was 16.8 years.
      Forty-six (54%) were female. Only 26 (30%) reported an intact family of origin.
      Twenty-three (27%) had been in care. Mean age for first use of any illicit drug
      was 12.4 years, and for heroin was 14.8 years. The mean age of leaving school was
      14.4 years; 42 (49%) first tried heroin after leaving school. Forty-one (48%) had
      a history of homelessness. Forty-four (51%) had previously injected; 26 (30%)
      were currently injecting. Fifty-six (65%) had not been screened for blood-borne
      diseases; twenty-one (24%) subsequently tested positive for hepatitis C. Thirty
      eight (48%) had previous convictions; 33 (38%) were facing charges. Forty-five
      (52%) had previously seen a psychiatrist; nine (11%) had received inpatient
      psychiatric treatment. Boys were more likely to leave school early, have a
      substance-abusing sibling, and to have a past conviction. Girls were more likely
      to have a partner, and have taken a deliberate overdose. CONCLUSIONS: This study
      highlights the multiple and complex needs of teenagers abusing opiates. Services
      seeking to meet their needs will require a broad range of interventions and
      excellent interagency co-operation.

PMID- 30290525
TI  - Male secondary school student's attitudes towards using mental health services.
AB  - OBJECTIVES: The rate of suicide among young men is rising. However, young men are
      reluctant to use mental health services. In this study we explored young men's
      attitudes towards mental illness and mental health services, as well as their
      willingness to use these services. METHODS: Four focus groups were conducted in
      two Dublin schools. A total of 18 students participated in the study. RESULTS:
      Students held negative views towards mental health services, particularly in
      respect to psychiatric hospitals and medication. Students were not well informed
      about whom to contact if they had depression and were very conscious about the
      stigma of going to see a 'professional'. Many students did not recognise
      depression as being a mental illness and could not differentiate between
      depression and feeling sad. CONCLUSIONS: This study shows that a lack of
      knowledge and understanding about mental illness, combined with prejudice against
      mental health professionals and fear of stigma, are important barriers to access
      of mental health services for young men.

PMID- 30290526
TI  - A survey of old age psychiatry consultation/liaison services in Ireland.
AB  - OBJECTIVES: The aim of this survey was to assess current structures for provision
      of consultation/liaison services to older people in the Republic of Ireland, and
      to ascertain the proportion of referrals to psychiatry of old age arising from
      consultation/liaison referrals. METHODS: A postal questionnaire was sent to the
      19 public sector, old age psychiatry services, operating in 2005. Information was
      obtained from 15 of these 19 services regarding the referrals they received in
      2005. FINDINGS: Consultation/liaison referrals make up 36% of total referrals to
      psychiatry of old age services. Two of 14 services had ring-fenced resources for
      consultation/liaison work. Three of 14 consultants described their service as
      having a significant liaison component. Location of the service and the criteria
      for accepting a referral are associated with the proportion of referrals that are
      consultation/liaison. CONCLUSIONS: Consultation/liaison referrals make up a
      significant proportion of referrals. To provide an effective consultation/liaison
      service ring-fenced resources are required. Despite this recent long term
      strategies for national service development have neglected this area.

PMID- 30290527
TI  - Clarithromycin induced mania.

PMID- 30290528
TI  - Somatoform disorder: a raison d'etre for liaison psychiatry.

PMID- 30290529
TI  - Attitudinal change toward psychiatry during undergraduate medical training in
      Ireland.
AB  - OBJECTIVES: This study examined the impact of psychiatric teaching on attitudes
      toward psychiatry of a cohort of medical students by means of a questionnaire
      survey. The impact of social desirability bias on questionnaire responses was
      also explored. Gender and nationality subgroups in the cohort were examined in
      more detail to determine whether these variables had any bearing on attitude
      change. METHODS: Fifth year medical students at NUI Galway completed the
      Attitudes to Psychiatry-30 questionnaire at the beginning and end of the
      psychiatric curriculum. This was coupled to the Marlowe-Crowne Social
      Desirability Scale (13 items) to determine the effect of this potential bias on
      responses to the attitudinal scale. Anonymity was ensured by using unique
      identification codes on the questionnaires, which facilitated individual
      comparisons of pre- and post-teaching responses. RESULTS: Attitudes toward
      psychiatry were positive prior to training but significantly improved following
      the teaching programme. There was no difference in attitudinal change between
      male and female subgroups. While students from outside the EU did show an
      improvement in mean scores on the ATP-30 this increase failed to reach
      significance. This finding was in contrast to the results for students from EU
      states whose mean increase on the ATP-30 was highly significant. Social
      desirability questionnaire scores fell significantly between the first and second
      administration, lending support to the findings being a true reflection of the
      students' attitudes toward psychiatry. CONCLUSIONS: These findings suggest that a
      teaching programme has the ability to influence students' attitudes. This is
      encouraging for recruitment into psychiatry and overall patient care.

PMID- 30290530
TI  - The Gloucester assertive community treatment team: A description and comparison
      with other services.
AB  - : Assertive Community Treatment (ACT) has developed globally as a model of
      community care for the severely mentally ill. However, in the United Kingdom
      there is mixed evidence regarding improvements in outcome and concerns about ACT
      teams having poor fidelity to the original ACT model. OBJECTIVE: This study
      presents the fidelity characteristics of an established ACT team serving
      Gloucester City. It describes service user demographic and illness data and
      compares these findings to other important studies in the United Kingdom. METHOD:
      The Dartmouth Assertive Community Treatment Scale was applied to rate the
      Gloucester ACT team's fidelity characteristics. The Gloucester Caseload Project
      Demographic Pro-Forma was collected from all of the team's 79 service users.
      RESULTS: The population of severely mentally ill ACT service users in Gloucester
      City were an older and more "disabled" group compared to the classic ACT studies.
      Furthermore, although findings indicate a high level of fidelity to the original
      ACT model, the team it is still associated with high levels of inpatient
      treatment. CONCLUSION: High fidelity ACT services appear to be associated with
      high admission rates. Therefore teams should not be viewed as alternatives to
      hospital admission but have goals of improving engagement and social functioning.
      Furthermore, findings have allowed the team to benchmark its service and target
      areas for further service development. More consistent reporting of fidelity data
      on ACT research would facilitate comparison across different services.

PMID- 30290531
TI  - Views of family carers to the future accommodation and support needs of their
      relatives with intellectual disabilities.
AB  - OBJECTIVES: The demand for places in supported accommodation is likely to rise
      due to the increasing longevity of people with intellectual disabilities and as
      their parents become unavailable or unable to care for them. However few attempts
      have been made to ascertain carer's views on alternative accommodation. METHOD:
      Four studies were undertaken in Northern Ireland to ascertain carer's views using
      three different methods. In all, 387 carers participated with the response being
      greatest for individual interviews conducted in the family home and least for
      self-completed questionnaires and attendance at group meetings. RESULTS: The
      majority of carers envisaged the person continuing to be cared for within the
      family. The most commonly chosen out-of-home provision was in residential or
      nursing homes, living with support in a house of their own and in homes for small
      groups of people. Few carers chose living with another family. However only small
      numbers of carers envisaged alternative provision being needed in the next two
      years and few had made any plans for alternative living arrangements.
      CONCLUSIONS: The implications for service planning are noted, primarily the need
      for individual reviews of future needs through person-centred planning; improved
      information to carers about various residential options and their differential
      benefits, along with more services aimed at improving the quality of life of
      people living with family carers. These need to be underpinned by a commitment of
      statutory agencies to partnership working with family carers. The implications
      for mental health services are noted.

PMID- 30290532
TI  - Older people with enduring or recurrent severe mental illness in the Eastern
      Region of Ireland.
AB  - OBJECTIVES: There has been no specific planning for older people with enduring or
      recurrent severe mental illness in Ireland. This survey aims to identify the
      number of affected over 65 year olds (graduates) and 55-64 year olds (prospective
      graduates) in the Health Service Executive, Eastern Region, their diagnoses and
      their use of psychiatric services. METHOD: A comprehensive survey of the ten
      general adult psychiatry and four old age psychiatry services in the (HSE)
      Eastern Region was undertaken for the year 2003 to determine the number of
      patients, their diagnoses and service utilisation. RESULTS: 649 people over 65
      years old were identified within the general adult psychiatry services and a
      further 279 within the old age psychiatry services giving a total of 928. (This
      number rose to 1141 after correcting for missing outpatient data.) 1,397 people
      between the ages of 55-64 were identified. (This number rose to 1,916 after
      correcting for missing outpatient data.) Conclusions: There are substantial
      numbers of 'graduates' and 'prospective graduates' in the Eastern Region. It is
      essential that services for this population are specifically planned for and
      further qualitative research is required to inform this process.

PMID- 30290533
TI  - Older people with enduring or recurrent severe mental illness (graduates): A
      literature review.
AB  - OBJECTIVES: To review the literature on older people with enduring or recurrent
      severe mental illness with an onset earlier than 65 years (graduates) and, in
      particular, to look at the specific features and needs of this group. METHOD: A
      Medline literature search produced 41 relevant papers and reports on the subject.
      RESULTS: There are a substantial number of older people with severe mental
      illness and the number will rise in line with increased longevity. As they age
      these patients' psychiatric disabilities are compounded by medical and social
      problems. The move to community based care has largely ignored the needs of
      graduates who were previously cared for in psychiatric institutions. CONCLUSION:
      There is an urgent need to plan and develop adequate services for this vulnerable
      group.

PMID- 30290534
TI  - Anorexia nervosa or otherwise? The usefulness of adult diagnostic systems in
      child and adolescent eating disorders.
AB  - We report on the case of a 15-year-old boy referred to Warrenstown inpatient unit
      for management of what appeared to be a typical case of anorexia nervosa. Over
      the course of his admission however, this diagnosis was no longer considered
      appropriate and substituted for a food avoidance emotional disorder. This is one
      of a number of cases of young males who have recently been referred for inpatient
      management of anorexia nervosa but which emerged into something quite atypical.
      The limited usefulness of the ICD-10/DSM-IV criteria in the diagnosis of an
      eating disorder in childhood and adolescence in this case reflects a broader
      level of discontent with the application of such diagnostic classification
      systems in a paediatric population.

PMID- 30290535
TI  - Oedipism: Auto-enucleation in a schizophrenic patient.
AB  - We report the rare occurrence of subarachnoid haemorrhage secondary to probable
      auto-enucleation of the orbit (oedipism) and we document management of these co
      incident pathologies in a schizophrenic patient. A 67 year old schizophrenic
      woman suffered a subarachnoid haemorrhage and presented with seizures following
      enucleation of her right eye. Initial efforts should focus on investigation and
      management of the subarachnoid haemorrhage. Management of Oedipism must include
      collaboration between psychiatrists, neurosurgeons and opthalmologists, focusing
      on management of the subarachnoid haemorrhage with precautions to prevent further
      self-injurious behaviour.

PMID- 30290536
TI  - Evaluating the need for a staff support/counselling service in a palliative care
      setting.

PMID- 30290537
TI  - Professor Anthony Clare: an appreciation of his contribution to psychiatry.

PMID- 30290538
TI  - The future of post-graduate training in psychiatry in Ireland: an address to the
      Irish Psychiatric Training.

PMID- 30290539
TI  - First admissions to inpatient care in Ireland for schizophrenia 1971-2004: trends
      in gender and age.
AB  - : First admissions for schizophrenia to inpatient psychiatric services in Ireland
      are declining. The reason for this decline has been debated and it has been
      proposed that it could be attributable to either a decline in incidence or to
      policy changes or to both. OBJECTIVES: This study examines the trends in first
      admission numbers for schizophrenia in Ireland and the influence of gender and
      marital status on age at first admission over the time period 1971-2004. METHOD:
      Data were derived from the National Psychiatric Inpatient Recording System
      (NPIRS) for the years 1971-2004 inclusive. All first admissions with a diagnosis
      of schizophrenia during these years were included in the analysis. RESULTS: The
      results showed a significant decline in the number of first admissions with the
      number of first admissions for males exceeding those for females. The average age
      of first admission was higher for females than males (p < 0.001). The average age
      of first admission showed a decline for males (p < 0.001), but not for females.
      Marital status was a stronger predictor of age of admission than gender (p <
      0.001). Never married persons had a lower age of first admission than those
      married and the delaying effect of marriage on age at first admission was evident
      in males and females (p < 0.001). CONCLUSIONS: An examination of first admission
      hospital data confirm male disadvantage in schizophrenia. The study highlighted a
      number of areas for future research which include examining gender differences in
      more refined diagnostic sub groups of schizophrenia and the monitoring of first
      contacts with community-based mental health services.

PMID- 30290540
TI  - Psychological health and well-being among young Irish adults.
AB  - OBJECTIVES: The aim of this study was to examine and describe levels of
      psychological health and well-being in a group of young people living in Dublin.
      METHOD: A sample of 97 young people (50 males, 47 females) were assessed for
      psychological status, suicidal ideation, substance misuse, contact with the law,
      self-esteem and locus of control as well as various social indicators such as
      educational attainment and social connectedness. A screening version of the
      Structured Clinical Interview for DSM-IV Axis Diagnosis (SCID) was used to assess
      psychological functioning and the Beck Scale for Suicide Ideation was employed to
      ascertain suicidal ideation. Self-esteem was measured using the Rosenberg Self
      Esteem Scale and locus of control was measured using a scale devised by Pearlin,
      Menaghan, Lieberman and Mullan (1981). RESULTS: Symptom levels were high and
      approximately one fifth of respondents had a probable psychiatric condition (most
      commonly depression or anxiety). Yet, only a small percentage was receiving
      treatment for psychiatric difficulties. Over half of the participants had used
      nonprescription drugs at some time. Alcohol consumption was high, especially
      amongst male respondents. Over half of those interviewed were categorised as
      misusing alcohol and/or drugs and participants greatly underestimated their level
      of alcohol use. Approximately one-quarter had had some contact with the law which
      was related to deficits in educational attainment and the latter variable was
      associated with childhood economic disadvantage. CONCLUSIONS: These findings
      suggest that among a sample of 97 young Irish people, a high level of psychiatric
      symptomatology and excessive use of alcohol is evident. This remains largely
      untreated as only a small percentage of the group had sought help for
      psychological difficulties which suggests a need to address the issues of mental
      health awareness, alcohol use and the accessibility of services. The paper also
      underlines the association between economic disadvantage and lack of educational
      attainment with associated linkages to offending.

PMID- 30290541
TI  - Toxic psychosis? Duration of untreated psychosis, symptomatology and cognitive
      deterioration in first episode psychosis.
AB  - OBJECTIVES: To examine the relationship between cognitive deficits, the duration
      of untreated psychosis (DUP) and positive and negative symptoms in a first
      episode psychosis sample. METHOD: We assessed a consecutive sample of first
      episode psychosis participants from a catchment area service with a comprehensive
      neuropsychology battery, a family and service-user based measure of DUP and
      measures of symptomatology. RESULTS: Using correlations and stepwise linear
      regressions, we found strong relationships between measures of DUP and positive
      symptomatology. We found that positive and negative symptoms were associated with
      different time periods within DUP. However, we did not find evidence of a
      relationship between DUP and cognitive factors. CONCLUSIONS: There was no
      evidence of a relationship between DUP and cognitive deterioration. However,
      there does appear to be evidence of a relationship between positive symptoms and
      aspects of DUP. These results highlight the importance of the heterogeneity of
      DUP and the potential to reduce positive symptoms through early intervention.

PMID- 30290542
TI  - Care of the mentally ill in Ireland in 1901 - the vindication of a policy.
AB  - This paper investigates the characteristics of those under inpatient psychiatric
      care in 1901 in the context of a policy formulated to provide institutional care
      and treatment for mentally ill persons. It presents data on admissions,
      discharges and deaths, their demographic and clinical characteristics and
      reported outcomes.

PMID- 30290543
TI  - Depression and cardiovascular disease: does antidepressant treatment improve
      cardiac outcome?
AB  - OBJECTIVE: The association between depression and cardiovascular disease has been
      well documented but the nature of this relationship continues to be defined.
      Given the accumulation of epidemiological evidence linking these diseases a
      number of interventional studies have been undertaken to assess the issue of
      whether antidepressant treatment in depressed patients with cardiovascular
      disease improves cardiac outcome. The objective of this paper is to review recent
      randomised controlled trials on this topic and to explore the implications that
      these may have for future research in this area. METHOD: This review is derived
      from a MEDLINE search using the search terms 'depressive disorder' and
      'cardiovascular diseases'. Only randomised controlled trials published in English
      with clearly defined methods and interventions are included here. Reference
      sections from the articles were used to identify additional relevant studies.
      RESULTS: A small number of high quality trials were uncovered which indicated
      mixed results in terms of the treatment of depression in cardiovascular disease.
      None indicated a statistically significant difference in cardiac outcome.
      CONCLUSIONS: It is not possible at this time to recommend treatment for
      depression to reduce cardiovascular risk. However depression remains prevalent in
      patients with cardiovascular disease and is a treatable cause of morbidity in its
      own right.

PMID- 30290544
TI  - Globus pallidus deep brain stimulators for a case of severe neuroleptic-related
      dystonia and dyskinesia.
AB  - We report a 45 year old man with neuroleptic-induced dyskinesia for whom deep
      brain stimulators (DBS) were implanted in the globus pallidus internus (GPi). We
      describe a significant improvement in his symptoms. Lastly, we review briefly the
      success of deep brain stimulation to date, and discuss the clinical implications
      for individuals who develop movement disorders during neuroleptic use.

PMID- 30290546
TI  - Intra-arterial injection of Zolpidem and substance misusers.

PMID- 30290547
TI  - Caffeine and suicide.

PMID- 30290545
TI  - Professor Anthony Clare.

PMID- 30290548
TI  - Re: Impact of Ramadan on treatment of psychosis.

PMID- 30290549
TI  - The challenge of applying mental health law reform to the intellectual disability
      sector in Ireland.
AB  - The full implementation of the Irish Mental Health Act 2001 brings about the
      introduction of an altered legal definition of mental disorder, mandatory review
      of involuntary detention within a 21-day period and new statutory rules regarding
      the use of seclusion and mechanical means of bodily restraint. This legislation
      came into full effect on November 1, 2006. The implications of this for the
      intellectual disability psychiatry sector are profound and the full ramifications
      of these changes will only become fully apparent over time. This also occurs at a
      time when we are facing unprecedented developments in government mental health
      policy, major changes to postgraduate training in psychiatry, difficulty
      recruiting appropriately skilled staff and increasing legal requirements on
      employers to ensure staff safety. Several of these drivers for change may appear
      at face value to be in conflict and a complex balance will be required if these
      changes are to be blended to ultimately improve the care provided to clients of
      our services.

PMID- 30290550
TI  - Determinants of duration of untreated psychosis in an Irish catchment area
      sample.
AB  - OBJECTIVE: To examine the variables that influence of duration of untreated
      psychosis (DUP) prior to presentation in persons with a first episode of
      psychosis. METHOD: Prospective examination of consecutive first presentations
      with DSM-IV psychosis attending a community based psychiatric service. RESULTS:
      One hundred and seventy-one patients had an average duration of untreated
      psychosis of 18 months and a median of five months. The mean duration of
      untreated mania was 1.5 months, median 0.75 months. DUP was predicted by social
      withdrawal and diagnosis in the total group and by prodrome in the
      schizophrenia/schizophreniform group. DUP was not associated with age at onset of
      psychosis, educational years or living status. CONCLUSIONS: There are significant
      differences in DUP between diagnostic groups. Increased social withdrawal is
      associated with a longer DUP.

PMID- 30290551
TI  - High prevalence of risk factors for physical illness in a long-stay psychiatric
      unit.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of risk factors
      for physical illness in a long stay psychiatric unit, where all care (both
      psychiatric and physical) is provided by the psychiatric team. METHOD: All
      patients in the long-stay ward had a full physical examination including
      calculation of BMI. All patients had blood sampling including FBC, U&E, LFTs,
      TFTs, lipid profile (total cholesterol, triglycerides, HDL and LDL), glucose,
      HbA1c, and prolactin. ATP111 criteria were used to determine the presence of the
      metabolic syndrome. RESULTS: We found the mean number of comorbid medical
      diagnosis was 2.7. The prevalence of metabolic syndrome was 40.7% (44.4% of
      females and 24.1% of males). The prevalence of obesity was 51%, and 51% also had
      a total cholesterols in excess of 5.0mmol/l. Prolactin was elevated in two-thirds
      of female patients. CONCLUSION: We conclude that the annual physical examination
      is of limited value in long-stay psychiatric unit. The high prevalence of
      physical illness and physical risk factors warrants primary care involvement in
      screening and treatment of long-stay psychiatric patients.

PMID- 30290552
TI  - Point prevalence of diabetes, obesity, hyperlipidaemia, hypertension and smoking
      in outpatients on clozapine.
AB  - OBJECTIVES: Patients with schizophrenia are known to be at higher risk than the
      general population of cardiovascular disease. Clozapine has been associated in
      the literature with high levels of cardiovascular risk factors such as weight
      gain, diabetes, hyperlipidaemia and hypertension. We set out to determine the
      prevalence of these risk factors in a population of Irish psychiatric patients.
      METHOD: In February 2006 we measured body mass index, fasting blood glucose,
      haemoglobin A1c (HbA1c), lipid levels, mean blood pressure and smoking rates
      among all outpatients prescribed clozapine attending an urban, community based
      mental health service. RESULTS: There were 50 outpatients (33 male; 17 female) on
      clozapine and they had been taking it for a mean of 5.4 years (mean daily dose
      428.8mg). The mean body mass index was 28.3. Patients had gained a mean of 8kg
      since commencing clozapine. One patient had been diagnosed with diabetes. Of the
      other 49 none met diagnostic criteria for diabetes. The mean fasting blood
      glucose was 5.5mmol/l and the mean HbA1c was 5.7%. One patient was on treatment
      for hyperlipidaemia. The mean fasting cholesterol among the other 49 patients was
      5.4mmol/l, while the mean fasting triglycerides was 2.1 mmol/l. Thirty (61.2%)
      had a fasting cholesterol greater than 5.0mmol/l, while 18 (36.7%) had
      triglycerides of greater than 2.0mmol/l. Three patients were on treatment for
      hypertension. Thirty-six of the 50 (72%) smoked (mean 13 cigarettes per day).
      CONCLUSIONS: The prevalence of obesity, diabetes, hyperlipidaemia and
      hypertension in this population was high but lower than might have been expected
      from US studies. It is important that cardiovascular risk factors are closely
      monitored and actively addressed in this at risk population.

PMID- 30290554
TI  - Suicide and the reluctance of young men to use mental health services.
AB  - Young men are grossly over represented in Irish suicide statistics, yet this
      group is the least likely to use mental health services. This paper outlines why
      young men are reluctant to access mental health services, framing the problem in
      the context of risk factors for suicide such as binge drinking and social change.
      The paper argues that de-stigmatising mental illness and encouraging young men to
      seek help for emotional problems should be a priority for policymakers.

PMID- 30290553
TI  - The homeless mentally ill - an audit from an inner city hospital.
AB  - OBJECTIVE: To determine the proportion of those that are homeless attending the
      Mater Misericordiae Hospital's (MUH) psychiatric service, including those
      presenting to accident and emergency who were homeless, and to compare the
      homeless group with the non-homeless so as to obtain a profile of this group.
      METHODS: All adults over 16, referred for psychiatric assessment, attending A&E
      were included, as were those attending outpatient clinics, liaison consultations
      and inpatients in the psychiatric unit, in the six-month period from January to
      June 2003. Excluded were those who were under 16, who refused to participate, who
      did not speak English, those with a diagnosis of personality disorder and organic
      brain damage. Questionnaires were completed by psychiatric registrars and a
      community psychiatric nurse, with an ICD-10 diagnosis recorded on each
      individual, in consultation with the treating consultant psychiatrist. RESULTS: A
      total of 628 patients were seen in MUH during the study period, and 13.8% were
      homeless. Of the homeless, 56.3% were seen as emergency referrals in the A&E, 23%
      were inpatients (including the psychiatric unit and consultations in
      medical/surgical wards) and 20.7% were seen in the outpatient department. Of all
      the A&E referrals to psychiatry, 34.8% were homeless. The homeless presented most
      commonly in suicidal crisis (26.6%) compared with 12.5% in the non-homeless
      group. Substance-abuse disorders were the primary diagnosis in 42.3% of the
      homeless group, accounting for 14.2% in the housed sample. Outcome for both
      groups was similar, with slightly more homeless being referred for psychiatric
      admission (17.8%), as compared to 12.0% in the nonhomeless group. CONCLUSIONS:
      Mental illness and the need for psychiatric services remain a serious issue for a
      significant segment of the homeless population. The homeless are overrepresented
      in our accident and emergency department, with their psychological and medical
      needs not being met in primary care. An integrated multi-disciplinary treatment
      approach, including outreach work, that addresses their many needs, appears to
      hold the greatest promise of success in this population.

PMID- 30290555
TI  - Integrating mental health and primary care services: a challenge for psychiatric
      training in Ireland.
AB  - A Vision for Change, the report of the Expert Group on Mental Health Policy
      asserts as one of its key recommendations the enhancement and formalisation of
      links between specialist mental health services and primary care. As part of a
      higher training post in psychiatry a consultation-liaison service was provided by
      a senior registrar in three rural general practices. This paper describes the
      experience of this initiative from an educational perspective and discusses the
      broader implications for Irish psychiatric training. With an emerging emphasis on
      collaborative mental health care there needs to be an appreciation of the
      specific set of skills that psychiatry trainees must learn in order to be
      effective in primary care settings. The tandem development of the appropriate
      services and training in an Irish context will require dedicated funding and
      resources.

PMID- 30290556
TI  - Characteristics of patients admitted to psychiatric intensive care units.
AB  - OBJECTIVE: A paucity of research exists on the types of patients admitted to
      psychiatric intensive care units (PICUs), which is important in terms of
      identifying patient needs, training and service provision. Questions have also
      been raised as to whether or not ethnic minorities are overrepresented in these
      units. METHOD: A literature review using MeSH headings from a wealth of databases
      was performed to identify such studies. In addition studies on ethnic minority
      overrepresentation in psychiatric care were also identified. RESULTS: Under a
      dozen studies were identified, mainly from the UK and Australia. Study designs
      tended to be basic and heterogeneous, but this was reflected in the nature of the
      study and the data gained. A typical PICU patient emerged, namely a young
      schizophrenic detained male, belonging to an ethnic minority (if in an inner
      city), known to mental health services with previous informal, detained and PICU
      admissions, admitted due to violence and often possessing a forensic history. If
      a complex need existed, it was usually substance misuse. The inpatient stay
      tended to be for less than two months and discharge was usually to an acute ward.
      Ethnic minorities were overrepresented in PICU care. CONCLUSIONS: The literature
      review highlighted a paucity of good-quality studies in this field. The
      establishment of a national association of intensive care units as well as
      national guidelines can only improve services. The reason for ethnic minority
      over-representation on these units is still far from clear.

PMID- 30290557
TI  - Psychosis? Beware - case series of clarithromycin and psychosis.
AB  - We describe two case reports presenting approximately one year apart These
      indicate a possible association between clarithromycin and psychosis. Such an
      association presents new challenges for clinicians based in non-psychiatric
      hospital settings and primary care physicians.

PMID- 30290558
TI  - Psychiatric assessment of HIV in a person with intellectual disability.

PMID- 30290559
TI  - Neuropsychiatry of epilepsy.

PMID- 30290560
TI  - First episode schizophrenia in general practice: a national survey.
AB  - OBJECTIVE: We sought to establish the views of general practitioners about
      detecting and managing patients with a first episode of schizophrenia in Ireland.
      METHOD: Twenty per cent of GPs were invited to participate in a cross-sectional
      postal survey. RESULTS: Sixty-two per cent (n = 261) participated. Almost all
      (99.2%) see at least one case of suspected first episode schizophrenia annually.
      The most commonly (80.7%) encountered symptom is 'bizarre behaviour'. Many
      (47.7%) rarely or never prescribe antipsychotics to patients whom they suspect
      have a first episode of schizophrenia. However, 80.6% of GPs reported that they
      'always' refer this group of patients to psychiatric services. Over half (57.8%)
      advised patients with schizophrenia to continue medication for less than a year.
      A large number of respondents reported that it is difficult to obtain a rapid
      psychiatric assessment. CONCLUSIONS: GPs want more information about identifying
      early psychosis, a closer liaison with psychiatric services and a rapid
      intervention service.

PMID- 30290561
TI  - Temporal trends in rates of dual diagnoses at a Canadian addictions hospital over
      a five-year period.
AB  - OBJECTIVES: Dual diagnosis refers to co-occurring substance use and psychiatric
      disorders. The principal aims of this investigation were two-fold: 1) to identify
      aspects of patients' drug use and prior treatment histories associated with their
      receiving a dual diagnosis upon admission to the Donwood Institute, a residential
      drug treatment facility located in Toronto, Canada; 2) to track temporal trends
      in the rates of diagnosed comorbidities over a five-year period at this same
      institution. METHODS: We conducted an analysis of the intake assessment forms and
      hospital records of 159 patients who had been admitted to a drug treatment
      facility during the month of September for each of the years between 1998 and
      2002 inclusive. Comparisons were made between patients who had received a
      psychiatric diagnosis on admission and patients who had received no such
      diagnosis. We then employed logistic regression analyses to explore the
      relationship of the variable psychiatric diagnosis on admission to other patient
      variables. RESULTS: Among the patients studied in our sample, those receiving
      psychotherapy or taking prescription psychotropic medication at the time of their
      admission as well as patients whose primary problem substance was cannabis or who
      had been previously admitted to the treatment facility were significantly more
      likely to have received a psychiatric diagnosis on admission, in spite of our
      finding that several patients receiving psychotherapy or taking at least one
      psychotropic medication did not receive a psychiatric diagnosis on admission.
      CONCLUSIONS: Whilst our data indicate that psychiatric comorbidity is common
      among individuals in treatment for substance use disorders at the Donwood
      Institute, it is possible that some individuals with psychiatric illness in our
      sample were not diagnosed as such when presenting for treatment of their
      substance use difficulties. Moreover, temporal tracking of rates of dual
      diagnoses did not reveal a consistent increase during the period studied.

PMID- 30290562
TI  - The point-prevalence of alcohol use disorders and binge drinking in an Irish
      general hospital.
AB  - OBJECTIVES: There is a paucity of data concerning the prevalence of alcohol use
      disorders and binge drinking in the general hospital adult population in Ireland.
      We therefore examined the point-prevalence of alcohol use disorders and of binge
      drinking in the adult inpatient population of the acute wards of an Irish
      university teaching hospital. The secondary aim was to examine gender, age, and
      patient group (medical/surgical) as risk factors. METHOD: We administered the
      Alcohol Use Disorders Identification Test (AUDIT) to all consenting patients (n =
      126) on the acute adult medical and surgical wards over one day. RESULTS: 76% of
      all inpatients on the acute medical and surgical wards were interviewed (n = 126)
      using the AUDIT. Of the subjects 28% screened positive for an alcohol use
      disorder. Of these 91% were identified as binge drinkers. A further 8% of the
      subjects screened positive for binge drinking but were not identified as having
      an alcohol use disorder. Overall, 36% of the subjects screened positive for
      either an alcohol use disorder and/or for binge drinking using the AUDIT. Male
      gender and under 65s were risk factors for both alcohol use disorders and binge
      drinking. CONCLUSIONS: The high point-prevalences of alcohol use disorders and
      binge drinking in hospital inpatients in particular are a cause for concern as
      they may have illness complicated by or secondary to undiagnosed alcohol excess.
      As this population is an easily accessible group for screening, and clinical and
      economic evidence supports intervention, we recommend screening all acute
      hospital admissions for alcohol use disorders and binge drinking, followed by
      appropriate management.

PMID- 30290563
TI  - Telepsychiatry in a Child and Adolescent Psychiatric Service.
AB  - OBJECTIVES: To carry out a survey on the use of video conferencing equipment by a
      rural child psychiatric multidisciplinary team and to determine what impact the
      introduction of this equipment had on service provision. METHOD: Several aspects
      were studied including user satisfaction and estimations of cost saving, on the
      basis of avoidance of travel to and from the regional base in Galway. A
      questionnaire was also developed to determine whether alternative contact would
      have been made if if this new technology were not in place. RESULTS: The results
      of the initial six months following commencement were investigated. Use of the
      equipment was attempted 17 times during this period. Most members of the child
      psychiatry team participated in its use. Visual problems accounted for 66.7% of
      reported technical difficulty and 88.9% of users rated their level of
      satisfaction with the equipment as 'Satisfied' or 'Very Satisfied'. CONCLUSIONS:
      Apart from the start-up cost implications of installing this equipment, it
      satisfied its aim of increasing contact between the rural service and St Anne's
      Children Centre in Galway. The equipment was easy to use and for the most part
      reliable.

PMID- 30290564
TI  - Bipolar affective disorder: advances in genetics and mood-stabilising medication.
AB  - The lifetime prevalence of bipolar affective disorder is between 1 % and 2%. This
      educational review paper focuses on two areas of interest and relevance to
      trainees preparing for the membership examination of the Royal College of
      Psychiatrists: (a) advances in the genetics of bipolar affective disorder; and
      (b) mood-stabilising medication in bipolar affective disorder.

PMID- 30290565
TI  - Suicidal behaviour and cognitive problem solving therapy: theory, application and
      review.
AB  - Suicidal behaviour is a major public health problem worldwide, both with regard
      to mortality and treatment of clients who have deliberately harmed themselves. It
      is a multifaceted problem resulting from complex interactions between social,
      biological and psychological factors. There is insufficient evidence on which to
      make firm recommendations about the most effective forms of treatment This is
      remarkable considering the extent of the problem worldwide, and the importance of
      dealing with it appropriately in order to prevent further suicides.

PMID- 30290566
TI  - Music therapy in the treatment and management of mental disorders.
AB  - OBJECTIVES: An increasing number of research studies support the benefits of
      providing music therapy in addition to standard treatment for people who have
      mental disorders. The objective of this paper was to review and summarise recent
      research findings in relation to this work. METHOD: A review of music therapy
      studies published since 1994 was undertaken. Criteria for including papers were
      that they a) were published in English in an indexed, peer-reviewed journal, and
      b) were conducted as a randomised controlled trial (RCT) or a controlled trial
      (CT), or c) provided a meta-analysis of existing studies. The large number of
      papers pertaining to music therapy for older adults who have mental disorders,
      including Alzheimer's disease and other types of dementia was not included.
      RESULTS: The findings support a role for music therapy as a structured
      interaction that patients are able to use to participate successfully, manage
      some of their symptoms, and express feelings relating to their experiences. Music
      therapy is demonstrated to be a beneficial intervention for people who have
      enduring mental illness. Music therapy invites and encourages participation from
      people of lower functioning levels and employs a non-verbal medium with which
      people have prior positive associations and in most cases have lifelong
      experience of using music for self-expression and pleasure. Additionally, the
      available peer reviewed literature supports the proposition that clinical
      outcomes are available through the use of music therapy intervention in
      conjunction with standard, well-established treatment methods. CONCLUSIONS: Music
      therapy is beneficial for patients receiving care for mental disorders and
      establishing this therapy within mental health service provision should be
      considered.

PMID- 30290567
TI  - An Irish case of pulmonary emboli secondary to clozapine therapy.
AB  - BACKGROUND: Clozapine is the prototype atypical antipsychotic used for treatment
      resistant schizophrenia, but its use has been limited by the well-established
      association with agranulocytosis. An increased risk of other serious adverse
      events such as myocarditis and thromboembolism has also been suggested to be
      associated with clozapine therapy. AIMS: We describe an Irish case of multiple
      pulmonary emboli detected by CT pulmonary angiogram thought to be secondary to
      clozapine therapy. CONCLUSION: Although clozapine is a very efficacious
      antipsychotic its many side-effects limit its use. Pulmonary embolism must be
      remembered as a potential rare side-effect in clozapine therapy. Underlying
      mechanisms are still unclear although several have been proposed.

PMID- 30290568
TI  - Bullying and mental health in national school children.

PMID- 30290569
TI  - Absence of dissociative disorders in Irish journals.

PMID- 30290570
TI  - The psychological health of clergy in Ireland - who cares for the carers?

PMID- 30290571
TI  - Meditation, mindfulness and mental health.

PMID- 30290572
TI  - The impact of a rehabilitation and recovery service on patient groups residing in
      high support community residences.
AB  - OBJECTIVES: To describe the characteristics of the patient groups with severe and
      enduring mental illness residing in high support community residences in Dublin
      North East Mental Health Service and the impact of a rehabilitation and recovery
      service on their outcomes since the instigation of that service. METHOD: Data was
      collected retrospectively on current and past residents from case notes and staff
      interviews. Data included demographics, psychiatric history and results of
      rehabilitation interventions. The results were compiled and analysed using
      descriptive statistics. RESULTS: Fifty patients were identified. The majority
      were male (62%) with a diagnosis of paranoid schizophrenia (66%).The levels of co
      morbid alcohol and drug misuse were 48% and 36% respectively. Histories of
      verbal/physical aggression were found in 70% and noncompliance in 60%. Two thirds
      of patients had a past history of being detained under the Mental Treatment Act
      (1945). Ninety-four per cent were unemployed at admission to the residence and
      following rehabilitation intervention 60% were linked with vocational training
      programmes and 10% with community employment schemes. 'New long-stay' and 'old
      long-stay' patients showed a trend towards poorer outcomes, whereas patients who
      had previously lived in the community showed a trend towards progressing to lower
      levels of support. CONCLUSIONS: Positive outcomes were achieved following active
      rehabilitation interventions, but there remained a cohort of patients whose needs
      could not be met in a supported community rehabilitation residential programme.
      This highlights the need to ensure that a range of rehabilitation services from
      inpatient to supported community placement are provided to meet the needs of
      patients with severe and enduring mental illness with complex needs.

PMID- 30290573
TI  - Routine investigations in paediatric psychopharmacology.
AB  - OBJECTIVES: This study examines (1) what are the minimum accepted baseline
      investigations recommended in the literature prior to prescribing in child
      psychiatry and (2) whether these investigations are routinely performed. METHOD:
      Medical literature on prescribing in child and adolescent psychiatry was
      reviewed, and a list of minimum baseline investigations recommended in the
      literature was established. A postal survey was performed to establish what
      current clinical practice is among child and adolescent psychiatrists. Current
      practice was compared with the recommendations in the literature. RESULTS: There
      are nine minimum accepted baseline investigations which are consistently
      recommended in the literature on child psychiatry. Six investigations are
      routinely performed by over 75% of respondents. However only 30% (n = 16)
      reported that they 'always' carried out eight or more of the nine recommended
      minimum investigations. CONCLUSIONS: A consensus statement is necessary,
      providing a list of recommended investigations prior to prescribing in child and
      adolescent psychiatry. Continuing medical education can then highlight the
      importance of these investigations.

PMID- 30290574
TI  - Admissions to a national forensic hospital 1997-2003.
AB  - OBJECTIVES: We set out to review all admissions from the criminal justice system
      to the Central Mental Hospital from January 1997 to December 2003, with
      particular attention to patient diagnoses, offences, source of admission, length
      of stay, and patterns of discharge. This study was undertaken to assist with
      future service planning and determination of resource needs. METHODS: The service
      maintains a combination of electronic and handwritten records of all admissions.
      Information was extracted concerning all admissions from January 1, 1997 to
      December 30, 2003. The data was analysed using a statistical package, SPSS 11.0
      for Windows. RESULTS: Nine hundred and eighty-six admissions of 780 individuals
      from the criminal justice system were recorded from January 1997 to December
      2003. There has been an increase in the proportion of patients admitted suffering
      with severe mental illness. There has also been a significant shift in the
      pattern of discharges, with a higher proportion of patients leaving to return to
      their local hospital. The proportion of admissions returned to prison has fallen
      from 91.1 % in 1999 to 64.7% in 2003, while 3.3% of individuals admitted became
      new long-stay cases. CONCLUSIONS: A shift in the profile of patients admitted in
      recent years reflects changes within the National Forensic Mental Health Service.
      An increased provision of regular and structured psychiatric input to the prisons
      has facilitated the identification of prisoners with mental illness. The shift
      from prison liaison to diversion from the Criminal Justice System to mental
      health services is however in its early stages.

PMID- 30290575
TI  - Analysis of referral letters to a department of old age psychiatry.
AB  - OBJECTIVE: There is a paucity of literature on the content of referral letters to
      psychiatric services and few relating specifically to referrals to a department
      of old age psychiatry. There has been a significant increase in referrals over
      the last five years to this service, which may reflect the ageing population and
      a greater awareness of the service. Our objective was to evaluate the quality and
      legibility of information received, clarity of reason for referral and details of
      pre-referral management. METHODOLOGY: The clinical records of the first 100
      referrals in 2002 to this department were analysed. The referral letters were
      examined for the documentation of a number of demographic variables, reason for
      referral, interventions to date and level of urgency. RESULTS: The clinical
      records of nine patients did not have an identifiable referral letter at the time
      of this analysis. Of the remaining 91 analysed, 59% were referred by their GP,
      33% were inpatient liaison referrals and 8% from outpatient departments. In the
      majority, patients' details were given, however, only 30% included a phone
      number. Next-of-kin was mentioned in 29%. GP's name was included in 71% of
      referrals from OPD and 7% of liaison referrals. The level of urgency was stated
      in 19%. Whether a domiciliary or OPD visit would be more appropriate was stated
      in 22%. The reason for referral was clear in 75%, with 43% including some aspect
      of Mental State Examination, 7% had included a MMSE score, 1% mentioned level of
      suicide risk. Thirty-one per cent had pre-referral investigations and 45% had pre
      referral treatment documented. The letters were clearly legible in 73%.
      CONCLUSION: The information in the referral letter in many cases was insufficient
      to prioritise and expedite appropriate assessment. It is planned to introduce a
      proforma referral form, specific to old age psychiatry, which would include the
      information which is required and which would, hopefully, lead to a more
      efficient service.

PMID- 30290576
TI  - Childhood adversity and substance misuse.
AB  - There is a strong link between childhood adversity and subsequent substance
      misuse. We describe a case of childhood adversity consisting of physical and
      sexual abuse, experience of homelessness in childhood and adulthood, intimate
      partner violence and polysubstance misuse in a 32 year old woman currently
      attending the methadone maintenance programme in the Drug Treatment Centre Board,
      Trinity Court, Dublin. The relevant literature to the case is reviewed in
      relation to the aetiology and symptoms of this complex case.

PMID- 30290577
TI  - A 'silent' political protest by an asylum seeker presenting to an Irish
      psychiatric service.
AB  - We report a case of a male asylum seeker, protesting politically, who stitched
      his lips together, presenting to a psychiatric service for assessment. We review
      the literature in this area. Funding of psychiatric services to meet the complex
      needs of immigrants should be an integral part of service development.

PMID- 30290578
TI  - Environmental health or psychiatric rehabilitation.

PMID- 30290579
TI  - The Norman centenary.

PMID- 30290580
TI  - Anti-psychotic polypharmacy and combined high-dose anti-psychotic prescribing in
      schizophrenia.

PMID- 30290581
TI  - The Quality of Scholarly Published Material Based on Education is our Business in
      the Worldwide Information World.

PMID- 30290582
TI  - Planes of Reference for Orbital Fractures: A Technique for Reproducible
      Measurements of the Orbit on Computed Tomography Scans.
AB  - PURPOSE: Planes of reference for orbital fractures (PROF) was developed to
      standardize measurements made on orbital computed tomography scans. This study
      describes the use of PROF in determining the location along the orbital floor
      where the posterior ledge (PL) most commonly occurs. The transverse inclination
      and anterior-posterior inclination of the orbital floor will also be measured.
      METHODS: This study evaluates 104 patients with unilateral orbital fracture.
      Fifty-two patients had intact infra-orbital margin (IM) and 52 had fractured IM.
      Facial computed tomography scans were analyzed using Osirix Lite Digital Imaging
      and Communications in Medicine Viewer version 7.0.1 (Geneva, Switzerland). All
      skull positions were standardized by orientation according to Frankfurt and mid
      sagittal planes. Measurements of distance of PL from IM were determined in the
      sagittal view. Measurements of the inclination of the orbital floor in the
      transverse and anterior-posterior sections were done on the coronal and sagittal
      views respectively. RESULTS: For patients with intact and fractured IM, the mean
      distances of PL from IM were 22.1 mm (95% CI: 21.2-23.0) and 21.1 mm (95% CI:
      20.2-21.9) respectively. Mean transverse inclination was 19.4 degrees  (95% CI:
      18.3-20.5). Mean anterior-posterior inclination was 15.5 degrees  (95% CI: 14.5
      16.5). CONCLUSION: Planes of reference for orbital fractures is a simple and
      effective method to acquire standardized measurements of the orbital cavity on
      computed tomography scans. Understanding the commonest location of PL and the
      orientation of the orbital floor in 3-dimensional space allows surgeons to
      perform dissection with greater precision.

PMID- 30290583
TI  - Effect of Prior Radiotherapy on the Outcome of Submental Island Flap in Head and
      Neck Reconstruction.
AB  - The submental island flap is a new alternative to the reconstruction of various
      head and neck defects. But there has been a relative paucity of information about
      the use of this flap in irradiated patients. The authors present their
      preliminary experience in the use of this flap in irradiated and nonirradiated
      patients. Eighty-one patients (53 nonirradiated and 28 irradiated patients)
      underwent reconstruction with the submental island flap between March 2011 and
      August 2017. The authors have 13 patients of venous congestion (7 in
      nonirradiated and 6 in irradiated group), 7 patients of partial necrosis of the
      flap (4 in nonirradiated and 3 in irradiated group). The authors also have 3
      patients of transient paralysis of marginal mandibular nerve (2 in the
      nonirradiated and 1 in irradiated group), and 2 patients of pharyngo-cutaneous
      fistula in nonirradiated group. The authors have no cases of total flap loss,
      permanent paralysis of marginal mandibular nerve but have dehiscence of the
      submental area after harvesting the flap in an irradiated patient. When combined
      with the reported experience of other surgeons, the authors' preliminary
      experience showed that the submental island flap was an excellent alternative in
      the reconstruction of head and neck defects in both irradiated and nonirradiated
      patients because of its reliability, versatility, and relatively acceptable
      complications.

PMID- 30290584
TI  - Comparing Spontaneous Closure and Paper Patching in Traumatic Tympanic Membrane
      Perforations.
AB  - The authors aim to analyze the effects of oral antibiotic treatment for traumatic
      tympanic membrane perforations and to compare the outcomes of patients with
      traumatic tympanic membrane perforation after paper-patching procedure and
      spontaneous healing.In this study, 80 patients with traumatic tympanic membrane
      perforation diagnosed in the otorhinolaryngology emergency department and
      outpatient clinic from March 2010 to January 2015 were retrospectively reviewed.
      If the patient is diagnosed at first week and the edge of perforation is moist
      with blood, our routine procedure is paper-patching (group 1). However, if the
      patients reject treatment or delay in admission, the authors follow up patients
      for spontaneous closure (group 2). Some of the patients got oral antibiotics for
      7 days (amoxicillin/clavulanic acid, 1000 mg 2 times/d) while some others did
      not. Closure rates and effectivity of oral antibiotics were evaluated and
      compared between 2 groups.In total, 80 patients were analyzed. The closure rates
      of perforations were 95.2% for group 1 (n = 42) and 81.6% for group 2 (n = 38).
      Although the paper-patched patients (group 1) perforation closure rate (95.2%) is
      higher than the nontreated patients (group 2) closure rate (81.6%), it is not
      statistically significant (P > 0.05). Antibiotic administered 55 patients had a
      significantly higher closure rate (94.5%) than the 25 patients who are not
      treated with antibiotics (76%) (P = 0.023; P < 0.05).In patients with traumatic
      tympanic membrane perforations, spontaneous closure rate is quite high. This
      study showed us that antibiotherapy and paper-patch treatments increase the
      healing rates.

PMID- 30290585
TI  - Cavernous Sinus and Parasellar Region: An Endoscopic Endonasal Anatomic Cadaver
      Dissection.
AB  - The aim of this study was to investigate the neurovascular structures of the
      cavernous sinus with the endonasal endoscopic transpterygoid approach on fresh
      human cadavers. Additionally, the course of internal carotid artery (ICA) and
      relevant anatomy was thoroughly investigated to refine the anatomical landmarks,
      exposure difficulties, potential complications, and limitations using the
      endonasal endoscopic technique. This study was carried out at an otolaryngology
      department of a tertiary medical center between June 2014 and June 2015. The
      surgical dissection was performed on 10 fresh human cadaver specimens using
      paranasal sinus and skull base endoscopic instruments. Cavernous sinuses and
      parasellar area were explored via an endoscopic endonasal transpterygoid
      approach. Dehiscence was present in 5 (25%) cavernous ICAs. Projection of the
      cavernous ICA on the whole lateral sphenoid wall was prominent in 6 (%30)
      sphenoid sinuses. Anterior curve was prominent in 12 (60%) cavernous ICAs,
      whereas posterior was prominent in 7 (35%). Mean distance between the lateral
      wall of eustachian tube orifice and petrous ICA was 19.50 +/- 1.05 mm (range 18
      22 mm). Cranial nerves of the cavernous sinus showed no variation. Control of the
      ICA is critical during the endonasal endoscopic approach to the cavernous sinus
      and skull base. The vidian nerve is a reliable and important landmark to the
      petrous ICA in the transpterygoid approach. Dissection of the eustachian tube and
      its relation to the ICA has to be kept in mind during nasopharyngeal surgery.

PMID- 30290586
TI  - Thyroid Carcinoma Presenting as a Dural and Calvarial Metastasis Mimicking a
      Lipoma With Difficult Diagnosis of the Primary Lesion.
AB  - Calvarial and dural metastases of papillary thyroid carcinomas (PTC) are rarely
      reported in the medical literature. Most frequent calvarial metastases are seen
      to originate from lung, breast, and prostate cancers. Thyroid cancer metastases
      are generally well vascularized and cause destruction in the bone tissues. First
      choice of treatment in distant metastases of PTC is surgery and radioactive
      iodine treatment for the primary cause. Postsurgical radiotherapy is used in
      accepted and suitable patients.

PMID- 30290587
TI  - Associations of TCF7L2 gene polymorphisms with the risk of diabetic nephropathy:
      A case-control study.
AB  - The aim of the study was to explore the correlation between rs7903146 and
      rs290487 polymorphisms in transcription factor 7-like 2 (TCF7L2) gene and
      diabetic nephropathy (DN) in Chinese Han population.Polymerase chain reaction
      restriction fragment length polymorphism was used to determine genotypes of
      TCF7L2 polymorphisms in 90 patients with DN and 96 diabetes patients without DN.
      The linkage disequilibrium (LD) and haplotype analysis were performed with
      haploview software. Hardy-Weinberg equilibrium was assessed in the control group
      based on the genotype distributions of TCF7L2 polymorphisms. The genotype,
      allele, and haplotype distribution differences between the case and control
      groups were analyzed by chi-squared test, and odds ratio (OR) and 95% confidence
      interval (CI) were used to indicate the relative risk of DN.People carrying TT
      genotype of rs7903146 were more easily to be attacked by DN than CC genotype
      carriers (P = .02, OR = 4.26, 95% CI = 1.12-16.24). Meanwhile, T allele also
      showed 1.85 times risk to suffer from DN compared with C allele (OR = 1.85, 95%
      CI = 1.02-3.10). However, there was no significant difference in genotypes and
      alleles frequencies of rs290487 between 2 groups. The strong LD existed between
      the 2 single nucleotide polymorphisms and haplotype T-T (rs7903146-rs290487)
      increased the susceptibility to DN (OR = 2.63, 95% CI = 1.31-5.25).TCF7L2
      rs7903146 polymorphism may be associated with the susceptibility to DN in Chinese
      Han population, but rs290487 is not. Additionally, haplotype is also a risk
      factor for DN.

PMID- 30290588
TI  - Worldwide research productivity in the field of back pain: A bibliometric
      analysis.
AB  - BACKGROUND: This study aimed to show the world research productivity in the field
      of back pain and to help researchers follow the scientific development and
      promote the cooperation in this field. METHODS: Web of Science (WoS) database was
      searched from 1995 to 2016 without other restrictions. The keywords were as
      follows: "lumbar NEAR pain," "back pain," "dorsalgia," "backache," "lumbago,"
      "back NEAR disorder," and "discitis." The following information of retrieved
      articles was analyzed: countries/territories, journals, publication year,
      authors, citation reports, and institutions. Publication activity was further
      adjusted for countries by gross domestic product (GDP) and population size.
      RESULTS: A total of 50,970 articles were retrieved in WoS database from 1995 to
      2016. The United States published the biggest number of articles (16,818,
      33.00%), followed by England (4,582, 8.99%), Germany (3,871, 7.60%), Canada
      (3,613, 7.09%), and Australia (3,063, 6.01%). Sweden ranked the first after
      adjusted for publication, and Netherlands ranked the first after adjusted for
      GDP. Besides, there was positive correlation between total number of publications
      and GDP for each country (P < .05). Harvard University was the most productive
      institution (917, 1.80%), Maher CG was the most productive author (229, 0.45%)
      and Spine was the most popular journal (3605, 7.07%) in the field of back pain
      research. Moreover, the article titled "Clinical importance of changes in chronic
      pain intensity measured on an 11-point numerical pain rating scale" in Pain had
      the highest citations (1749). CONCLUSION: There was a significant increase in
      annual publications concerning back pain research worldwide. The total number of
      publications was positively associated with GDP in main productive countries. The
      United States was the most productive country, Harvard University was the most
      productive institution, Maher CG was the most productive author and Spine was the
      most popular journal in the field of back pain.

PMID- 30290589
TI  - Increased serum pentraxin-3 level predicts poor prognosis in patients with
      colorectal cancer after curative surgery, a cohort study.
AB  - Pentraxin-3 (PTX3) is a glycoprotein involved in inflammation and immune
      regulation of cancer. The aim of this study was to evaluate the serum PTX3 level
      in patients with colorectal cancer (CRC) and analyze its prognostic
      significance.A total of 263 consecutive patients underwent radical resection for
      primary CRC and 126 healthy controls were enrolled in this study. Serum PTX3
      level was measured within the day before surgery though enzyme-linked
      immunosorbent assays, comparing with the level of healthy control. Baseline
      demographic and clinical characteristics were recorded. The association between
      serum PTX3 level and survival outcome was analyzed by the Kaplan-Meier with Log
      Rank test and Cox regression methods.Mean serum PTX3 level in CRC patients was
      higher than that of healthy control (13.8 +/- 3.2ng/mL versus 3.3 +/- 1.2ng/mL, P
      < .001). Finally, 55 (20.9%) patients out of all 263 patients studied had died
      during following-up period. All patients were divided into 2 groups using the
      optimal cutoff value (12.6 ng/mL) of PTX3 level using a sensitivity of 68.0% and
      a specificity of 71.7% as optimal conditions from receiver operating curve
      analysis. Patients with a PTX3>=12.6ng/mL had poorer 5 years overall survival
      rate (76.6% versus 67.8%, P = .025) patients with a PTX3 < 12.6ng/mL in
      univariate analysis and serum PTX3 level also been confirmed as an independent
      predictor for survival for CRC in multivariate analysis (Hazard ratio, 1.468; 95%
      [confidence interval] CI, 1.081-1.976; P < .001).Serum PTX3 level can serve as an
      independent prognostic biomarker for CRC patients after curative resection.

PMID- 30290590
TI  - Malakoplakia as a cause of severe hypercalcemia through ectopic 25-hydroxyvitamin
      D3 1-alpha-hydroxylase expression: A case report.
AB  - RATIONALE: Malakoplakia is a rare disease characterized by the presence of
      nongranulomatous macrophage infiltration. In most cases, it affects the urinary
      tract. Malakoplakia can cause acute kidney injury when it is localized in the
      kidneys. PATIENT CONCERNS: Here, we report the case of a 65-year-old female
      patient with renal malakoplakia responsible for hypercalcemia. During her initial
      assessment, she was also diagnosed 25-OH vitamin D insufficiency, for which she
      was prescribed oral cholecalciferol. Three months later, she developed severe
      hypercalcemia with normal 25-OH vitamin D and parathyroid hormone levels and high
      1,25-dihydroxyvitamin D levels. DIAGNOSES: After a superimposed granulomatous
      disease was excluded, malakoplakia cells were suspected to be responsible for the
      abnormal 25-hydroxyvitamin D3 1-alpha-hydroxylase activity, which was confirmed
      by immunohistochemistry. INTERVENTIONS: Cholecalciferol was stopped, the patient
      was rehydrated with intravenous physiological saline, and prednisone was
      initiated to decrease the enzyme activity. OUTCOMES: Six months later, she
      displayed normal serum calcium, 25-OH vitamin D and 1,25-dihydroxyvitamin D
      levels. LESSONS: This case illustrates that malakoplakia may exhibit ectopic 25
      hydroxyvitamin D3 1-alpha-hydroxylase activity and cause severe hypercalcemia
      upon vitamin D supplementation. Therefore, such supplementation should not be
      given in malakoplakia patients without an actual deficiency and requires careful
      monitoring of serum calcium.

PMID- 30290591
TI  - Fatal case of hemophagocytic lymphohistiocytosis associated with group B
      streptococcus sepsis: A case report.
AB  - RATIONALE: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease
      characterized by an excessive systemic inflammatory response. HLH is classified
      as primary or secondary, where the latter may occur in association with many
      infections. However, no case of HLH has been previously associated with group b
      streptococcus (GBS) sepsis. PATIENT CONCERNS: We present a fatal case of HLH in a
      5-year-old girl with GBS sepsis. DIAGNOSIS: The present patient met 5 of the HLH
      criteria: fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or
      hypofibrinogenemia, and hyperferritinemia. GBS was identified in 2 sets of
      peripheral blood bacterial cultures. INTERVENTIONS: Empirical antibiotics,
      inotropes, and immunoglobulins were administered. OUTCOMES: The clinical course
      of the patient was fulminant and the patient died of septic shock 10 hours after
      admission to the hospital. LESSONS: We suggest GBS infection can cause HLH and
      early awareness of HLH associated with GBS infection and proper effective
      treatment are necessary to reduce mortality.

PMID- 30290592
TI  - Esophageal neuroendocrine carcinoma complicated with unexpected
      hyperprocalcitonin: Case report and literature review.
AB  - RATIONALE: Neuroendocrine tumors (NETs) with hyperprocalcitonin are relatively
      rare with a low incidence rate. PATIENT CONCERNS: An afebrile 63-year-old male
      with persistent low back pain unexpectedly presented with an extreme
      hyperprocalcitonin. Radiological assessment revealed thickening of the esophageal
      wall with vertebral bone destruction and liver lesions. Endoscopy showed an
      irregular-shaped esophageal lesion which turned out to be poorly-differentiated
      NETs. DIAGNOSIS: Esophageal NETs with multiple metastases. INTERVENTIONS: The
      patient was treated with chemotherapies, and was evaluated by procalcitonin level
      and radiology within follow-up. OUTCOME: The procalcitonin levels were altered in
      line with the therapeutic response and disease progression during the treatment
      course. LESSONS: Increased procalcitonin occurs in several malignancies with
      neuroendocrine components, such as NETs of the digestive system.

PMID- 30290594
TI  - Can radial bone mineral density predict spinal bone mineral density in patients
      with advanced Duchenne muscular dystrophy?
AB  - In advanced Duchenne muscular dystrophy (DMD), patients with high bone fracture
      risk due to osteoporosis, it is difficult to measure spinal bone mineral density
      (BMD) because of maintaining proper posture. This study began with the idea that
      if we diagnose and manage osteoporosis by predicting spinal BMD through easily
      testable radial BMD, we could prevent fracture and improve quality of life in DMD
      patients. In 61 DMD patients aged 20 years or older who were admitted to Gangnam
      Severance Hospital from April 2013 to May 2015, radial BMD and spinal BMD were
      measured to compare their Z-scores. In 45 patients, the z-score was less than 
      2.0 in spinal BMD defined as osteoporosis. And the optimal range of Z-score in
      the radius was -5.2 to -5.0 (sensitivity 78.9%, specificity 71.4%). Only through
      the radius BMD, spinal BMD can be predicted and we suggest appropriate times for
      treatments.

PMID- 30290593
TI  - Expressions of KAI1 and E-cadherin in nonsmall cell lung cancer and their
      correlation with vasculogenic mimicry.
AB  - BACKGROUND: Metastasis and recurrence are the most common reasons for treatment
      failure of nonsmall cell lung cancer (NSCLC). Vasculogenic mimicry (VM, new blood
      supply formation in malignant tumors), E-Cadherin (a calcium-dependent
      transmembrane glycoprotein that mediates intercellular adhesion), KAI1 (a
      suppressor gene of tumor metastasis) are all valuable factors for metastasis and
      prognosis in diverse common human cancers. However, the correlation of VM, E
      Cadherin, and KAI1 in NSCLC is still unclear. In this study, we analyzed the
      correlations among these factors as well as their respective correlations with
      clinicopathological parameters and survival in NSCLC. METHODS: The level of VM, E
      Cadherin, and KAI1 in 163 tissue samples of NSCLC was examined by
      immunhistochemistry. Clinical data were also collected. RESULTS: Levels of VM was
      significantly higher, and levels of KAI1 and E-Cadherin significantly lower in
      NSCLC tissues than in normal lung tissues. Levels of VM were positively
      associated with lymph node metastasis (LNM), size, grade, and tumor node
      metastasis (TNM) stages, and negatively associated with patients' overall
      survival (OS). Levels of KAI1 and E-Cadherin were negatively correlated with LNM,
      size, grade, and TNM stage, and positively associated with patients' OS. In
      multivariate analysis, high levels of VM, E-Cadherin, and KAI1, as well as TNM
      stages were independently correlated with lower OS in patients with NSCLC.
      CONCLUSION: VM and the expression of E-Cadherin and KAI1 may represent promising
      metastatic and prognostic biomarkers, as well as potential therapeutic targets
      for NSCLC.

PMID- 30290595
TI  - Risk factors related to metastasis of para-aortic lymph nodes in pancreatic
      ductal adenocarcinoma: A retrospective observational study.
AB  - This study was designed to explore the risk factors related to metastasis of para
      aortic lymph node (PALN).Clinicopathologic data of 241 patients with resectable
      or borderline resectable pancreatic cancer who underwent pancreaticoduodenectomy
      with extended lymphadenectomy between January 2008 and December 2015 were
      collected, potential factors related to metastasis of PALN were analyzed.Positive
      rate of PALN was 19.5% (47/241). Univariate analysis showed that back pain (P =
      .028), preoperative CA19-9 level (P < .001), tumor size (P < .001), portal vein
      (PV)/superior mesenteric vein (SMV) invasion (P < .001), superior mesenteric
      artery (SMA) invasion (P < .001), and diameter > 1.0 cm were in correlation with
      PALN involvement, multivariate analysis revealed that preoperative CA19-9 level,
      PV/SMV invasion, SMA invasion and diameter > 1.0 cm were independent risk factors
      to metastasis of PALN. Patients with LN8+ had a higher positive rate of PALN than
      with LN8- (38.1% vs 15.6%, P = .001), similar results could be found when LN12+
      (35.8% vs 13.2%, P < .001) and LN14+ (41.2% vs 11.0%, P < .001), multivariate
      analysis showed that LN8+ and LN14+ were closely in correlation with PALN
      metastasis.Several factors were related to the status of PALN, preoperative CA19
      9 level, PV/SMV invasion, SMA invasion and diameter > 1.0 cm were 4 independent
      risk factors to PALN metastasis. LN8+ and LN14+ were 2 strong predictors of PALN
      metastasis. A comprehensive analysis covering all possible risk factors related
      to metastasis of PALN should be given before design of treatment plan whenever
      involvement of PALN was suspected.

PMID- 30290596
TI  - Arthroscopic management of elbow synovial chondromatosis.
AB  - OBJECTIVE: We aimed to identify factors that affect pain, complications, and
      function following elbow arthroscopy for elbow synovial chondromatosis. METHODS:
      We retrospectively reviewed the cases of all patients with elbow synovial
      chondromatosis treated by arthroscopic synovectomy and loose body removal between
      January 2000 and January 2016 at our institution. Eleven patients were enrolled
      (8 male; mean age, 41.7 years). The mean duration of symptoms was 13.7 months,
      and all patients had a decreased range of motion (ROM) in the affected elbow. By
      Milgram criteria, there was 1 phase II case, and 10 cases were phase III.
      RESULTS: All patients were followed postoperatively (mean follow-up, 65 months).
      The preoperatively restricted ROM of 100 degrees  flexion (range, 78 degrees -120
      degrees ) and extension of 30 degrees  (range, 15 degrees -40 degrees ) were
      improved to 130 degrees  flexion (range, 120 degrees -140 degrees ) and -5
      degrees  hyperextension (range, -10 degrees -0 degrees ). Pain, recorded as the
      pain subscore of the American Shoulder and Elbow Surgeons questionnaire for
      elbows, was significantly improved from 32 points (range, 20-50) preoperatively
      to 85 (range, 70-100) postoperatively (on a scale ranging from 0 [worst pain] to
      100 [pain-free]). Recurrence occurred in 2 patients (18.2%) who then received
      arthroscopic synovectomy and loose body removal again. There were no fractures or
      neurovascular complications, and no patient developed an infection. CONCLUSION:
      Arthroscopic management of synovial chondromatosis of the elbow was an effective
      and safe therapeutic method. After the intervention, immediate and durable
      improvement of elbow function can be expected.

PMID- 30290598
TI  - Clinical observation of 60 cases of treating cognitive disorder after cerebral
      injury in combination with scalp acupuncture and cognitive training.
AB  - To observe the clinical effect of scalp acupuncture combined with cognitive
      training on cognitive disorder after cerebral injury.Around 60 cases of cerebral
      injury patients for hospitalization in rehabilitation department of Chongqing
      Three Gorges Central Hospital from July in 2015 to June in 2017 are divided into
      control group and treatment group of 30 cases for each at random. The control
      group received routine treatment and cognitive rehabilitation training for 12
      weeks. The treatment group received conventional treatment, cognitive
      rehabilitation training, and scalp acupuncture. Acupuncture with a scalp
      acupuncture is provided for the treatment group besides adopting above
      conventional treatment and rehabilitation training method.Loewenstein
      Occupational Therapy Cognitive Assessment (LOTCA) score of both groups increases
      obviously after treatment compared with that before treatment, and there is
      difference (P < .01) through contrast. And LOTCA score of treatment group is
      higher than that of control group (P < .05) after treatment.Scalp acupuncture in
      combination with cognitive training can effectively improve cognitive disorder
      degree of patients with cerebral injury, and the effect is more significant
      compared with simple cognitive rehabilitation training, thus it is worth of
      research and application.

PMID- 30290599
TI  - Renal resistive index and aortic knob width relationship as a predictor of renal
      prognosis in essential hypertension.
AB  - The scientific studies that have been conducted so far highlight that renal
      resistive index (RI) and aortic knob width (AKW) indicate poor prognosis
      regarding renal and cardiovascular mortality. But the existence of a direct
      relationship RI and AKW is unclear. This study aims investigating the
      relationship between RI and the measured AKW in chest radiography of the patients
      with hypertensive nephropathy who do not require renal replacement therapy.This
      prospective study included 268 consecutive patients with essential hypertension.
      Patients were divided into 2 groups as RI >=0.7 and RI <0.7. The ROC curve,
      sensitivity, and specificity ratios were evaluated to determine which AKW value
      is the best predictive one for the RI >=0.7.The cutoff point of AKW was evaluated
      as >=36 for the cases with RI >=0.7: sensitivity was 71.22%; specificity was
      71.32%; the positive predictive value (PPV) was 72.79; the negative predictive
      value (NPV) was 69.70, and the accuracy was 71.27. Area under the ROC curve +/-
      standard error (AUC +/- SE) = 0.729 +/- 0.031 (P < .001).AKW can provide
      important predictive information about the subclinical renal dysfunction in
      hypertensive patients with RI >=0.7. Moreover; AKW is a predictive factor for
      both the diagnostic and prognostic evaluation of renal pathologies.

PMID- 30290597
TI  - Normal pregnancy induced glucose metabolic stress in a longitudinal cohort of
      healthy women: Novel insights generated from a urine metabolomics study.
AB  - During normal pregnancy, mothers face a unique physiological challenge in the
      adaptation of glucose metabolism in preparation for the metabolic stress
      presented by fetal development. However, the responsible mechanism remains
      elusive. The purpose of this study is to investigate the mechanism of the
      metabolic stress of glucose metabolism in pregnant women using metabolomics
      method.A Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass
      Spectrometer-based untargeted metabolomics study was performed to investigate the
      dynamic urinary signature of the intermediates of glucose metabolism in a
      longitudinal cohort of 232 healthy pregnant women in their first, second, and
      third trimesters.Twelve glucose metabolic intermediates were screened out from
      hundreds of candidate metabolites using partial least squares discriminant
      analysis models. These 12 markers were mainly involved in the metabolic pathways
      of insulin resistance, glycolysis/gluconeogenesis, tricarboxylic acid cycle,
      nonabsorbable carbohydrate metabolism, and N-glycan biosynthesis. In particular,
      L-acetylcarnitine, a metabolite that is beneficial for the amelioration of
      insulin resistance, decreased in a time-dependent manner during normal pregnancy.
      Moreover, thiamine pyrophosphate, an intermediate product of
      glycolysis/gluconeogenesis, significantly increased in the second trimester, and
      argininosuccinic acid and oxalosuccinic acid, intermediates involved in the
      tricarboxylic acid cycle, significantly decreased in the third trimester,
      suggesting an increased glucose demand in the maternal body during fetal
      development.These findings provide novel insight into the normal pregnancy
      induced elevation of insulin resistance and glycolysis/gluconeogenesis, as well
      as the observed reduction in the aerobic oxidation of glucose.

PMID- 30290600
TI  - Manifestations and outcomes of nocardia infections: Comparison of
      immunocompromised and nonimmunocompromised adult patients.
AB  - Nocardia is a ubiquitous environmental pathogen that causes infection primarily
      following inhalation into the lungs. It is generally thought to cause infection
      primarily in immunocompromised patients, but nonimmunocompromised individuals are
      also at risk of infection. We sought to compare risk factors, clinical
      manifestations, diagnostic approach, treatment, and mortality in
      immunocompromised and nonimmunocompromised adults with nocardiosis.We studied all
      adults with culture-proven Nocardia infection at a tertiary care hospital from
      1994 to 2015 and compared immunocompromised with nonimmunocompromised patients.
      The immunocompromised group included patients who had a solid organ transplant,
      hematopoietic cell transplant (HCT), hematological or solid tumor malignancy
      treated with chemotherapy in the preceding 90 days, inherited immunodeficiency,
      autoimmune/inflammatory disorders treated with immunosuppressive agents, or high
      dose corticosteroid therapy for at least 3 weeks before the diagnosis of
      nocardiosis.There were 112 patients, mean age 55 +/- 17 years; 54 (48%) were
      women. Sixty-seven (60%) were immunocompromised, and 45 (40%) were
      nonimmunocompromised. The lung was the site of infection in 54 (81%)
      immunocompromised and 25 (55%) nonimmunocompromised patients. Pulmonary
      nocardiosis in immunocompromised patients was associated with high-dose
      corticosteroids, P = .002 and allogeneic HCT, P = .01, and in
      nonimmunocompromised patients with cigarette smoking, bronchiectasis, and other
      chronic lung diseases, P = .002.Cavitation occurred only in the immunocompromised
      group, P < .001. Disseminated infection was more common in the immunocompromised,
      P = .01, and was highest in solid organ transplant recipients, P = .007. Eye
      infection was more common in nonimmunocompromised patients, P = .009. Clinical
      signs and symptoms did not differ significantly between the 2 groups. The initial
      treatment for most patients in both groups was trimethoprim-sulfamethoxazole with
      or without a carbapenem. All-cause 1-year mortality was 19%; 18 (27%)
      immunocompromised and 3 (7%) nonimmunocompromised patients died, P =
      .01.Immunocompromised patients with nocardiosis had more severe disease and
      significantly higher mortality than nonimmunocompromised patients, but clinical
      presentations did not differ.

PMID- 30290601
TI  - 99mTc-3PRGD2 single-photon emission computed tomography/computed tomography for
      the diagnosis of choroidal melanoma: A preliminary STROBE-compliant observational
      study.
AB  - Recent successes in monitoring and diagnosing a variety of tumors using Tc-PEG4
      E[PEG4-c(RGDfK)]2 (Tc-3PRGD2) single-photon emission computed tomography (SPECT)
      imaging encouraged us to expand the use of this tracer. This case-control study
      aimed to evaluate the feasibility of Tc-3PRGD2 imaging for detecting choroidal
      melanoma (CM) and for monitoring tumor response to plaque brachytherapy (PB). Ten
      consecutive patients with CM who underwent Tc-3PRGD2 imaging before and 3 months
      after PB were reviewed. The tumor-to-occipital bone (T/O) and mirrored
      contralateral normal tissue-to-occipital bone (N/O) ratios were calculated by
      region of interest analysis at baseline and 3 months post-PB. T/O values were
      compared between patients with CM with comorbid secondary retinal detachment (RD)
      and those without RD. The relationship between T/O value and tumor volume was
      also investigated. Tc-3PRGD2 SPECT/CT showed focal uptake in CM. The mean T/O
      ratio before PB was 1.90 +/- 1.26 and the mean N/O ratio was 0.80 +/- 0.21 (P =
      .02). The Tc-3PRGD2 concentrations in 5 patients with CM with RD were higher (T/O
      = 2.69 +/- 1.39) than in those without secondary RD (T/O = 1.10 +/- 0.18) (P =
      .008). T/O ratios at 3 months post-PB were significantly lower than that at
      baseline (1.23 +/- 0.59, P = .03). There was a linear relationship between T/O
      and tumor volume (y-hat = 0.028 + 0.003x, R = 0.768, P = .001). The 95%
      confidence interval for the (T/O)/volume ratio was 0.002 to 0.005. Tc-3PRGD2
      imaging is a feasible modality for the diagnosis of CM. Furthermore, follow-up
      for at least 20 months after PB indicated that coanalysis of Tc-3PRGD2 imaging
      and tumor volume may provide a promising prognostic predictor in patients with
      CM.

PMID- 30290602
TI  - Viabahn stent graft compared with prosthetic surgical above-knee bypass in
      treatment of superficial femoral artery disease: Long-term results of a
      retrospective analysis.
AB  - The prosthetic surgical above-knee bypass (pAKB) is a standard therapy in
      superficial femoral artery (SFA) occlusive disease in absence of suitable vein.
      Viabahn graft has been established as a promising alternative. Since limited
      comparative data are available, we conducted a retrospective study to compare
      long-term outcomes of these 2 therapies in a real-world setting.Records of 52
      patients (60 limbs), who were treated by pAKB (29 limbs) or Viabahn (31 limbs)
      were reviewed. Patients were followed up by clinical assessment, physical
      examination, and resting ankle brachial index (ABI) after 3, 6, 12 months and
      yearly thereafter. Long-term data were available for 97% in the Viabahn and 93%
      for pAKB after 73 +/- 3.7 months (mean +/- standard error [SE]).Long-term primary
      and secondary patencies in Viabahn group were 40% and 70%, respectively, after 63
      +/- 2.8 months (mean +/- SE). Total lesion length was 19 +/- 11.06 cm (mean +/-
      SE), graft size was 6 +/- 0.72 mm (mean +/- SE). Hospital stay was 4.8 +/- 0.72
      days (mean +/- SE). Limb salvage was achieved in 90%. Patients in the pAKB group
      showed a total lesion length of 24.39 +/- 1.97 cm (mean +/- SE), graft size was 7
      +/- 0.99 mm (mean +/- SE). Long-term analysis after 83 +/- 6.8 months (mean +/-
      SE) revealed a primary patency of 78% with a secondary patency of 94%. Hospital
      stay was 10.4 +/- 1.27 days (mean +/- SE). Limb salvage was ensured in 97%. Long
      term primary patency was lower for Viabahn (P = .044), secondary patency (P =
      .245), and leg salvage (P = .389) were not significantly different. However,
      hospital stay was shorter (P = .0002) for Viabahn.Long-term analysis of Viabahn
      revealed a significantly lower primary patency, a similar secondary patency, limb
      salvage, and significantly shorter hospital stay when compared with pAKB. Our
      data suggest that pAKB is still a valuable option in patients suitable for an
      open operation. However, Viabahn can be used as a less invasive treatment in high
      risk patients.

PMID- 30290603
TI  - The clinical efficacy of using autologous platelet-rich plasma in total hip
      arthroplasty: A retrospective comparative study.
AB  - This study evaluated whether intra-articular platelet-rich plasma (PRP) might
      prevent postoperative bleeding in total hip arthroplasty (THA).In this study, 260
      hips that underwent THA were evaluated randomly by paramedical staffs, 130 of
      which involved the intraoperative use of PRP, and 130 of which served as control
      group. Postoperative blood loss (drain bag volume), estimated blood loss, and
      change in hemoglobin (Hb) at day 1, 2, 4, and 7 were analyzed, respectively.PRP
      treated group had a significant decrease in mean postoperative blood loss (92.6
      +/- 168.2 mL) compared to control group (682.3 +/- 185.5 mL, P < .01). The mean
      postoperative estimated blood loss (526.1 +/- 236.1 mL) in the PRP-treated group
      was significantly less than that in the control group (629.2.2 +/- 142.3 mL, P <
      .01). There was a statistically significant difference in Hb value (mg/dL) at day
      1, 2, 4, and 7 (-1.35 vs -1.98, -1.59 vs -2.52, -1.96 vs -2.82, and -1.76 vs 
      2.47, P < .05).We found a significant reduction in postoperative blood loss
      (drain bag volume), estimated blood loss, and change in Hb after the use of
      autologous platelet gel in patients of THA, and PRP appears to be effective in
      reducing postoperative bleeding in THA.

PMID- 30290604
TI  - Pain monitoring and management in a rehabilitation setting after total joint
      replacement.
AB  - Total hip replacement (THR) and, particularly, total knee replacement (TKR), are
      painful surgical procedures. Effective postoperative pain management leads to a
      better and earlier functional recovery and prevents chronic pain. Studies on the
      control of pain during the postoperative rehabilitation period are not common.
      The aim of this study is to present results of a perioperative anesthetic
      protocol, and a pain treatment protocol in use in the Orthopaedic and the
      Rehabilitation intensive units of our Hospital. 100 patients (50 THR and 50 TKR)
      were retrospectively included in this observational study. Numeric Rating Scale
      (NRS) for pain at rest registered in the clinical sheet was retrieved for all
      patients and analyzed with respect to the spinal anaesthesia given for the
      surgery, local analgesia, analgesia protocol adopted during the postoperative
      days in the Orthopaedic Unit, the antalgic treatment given during the stay within
      the Rehabilitation Unit, the postoperative consumption of rescue pain medication,
      and any collateral effect due to the analgesic therapy. Patients reached standard
      functional abilities (walking at least 50 meters and climbing/descending stairs)
      at a mean length of 8 days without medication-related complications. Mean NRS
      during the time of stay was 1.3 +/- 0.3 for THR and 1.3 +/- 0.2 for TKR) and
      maximum mean NRS was 1.8 +/- 0.5 for TKR and 1.8 +/- 0.6 for THR. The use of
      rescue therapy in the rehabilitation guard was correlated with the mean NRS pain
      and the maximum NRS pain. A very good control of pain with the perioperative
      anesthetic protocol and pain treatment protocol in use was obtained.

PMID- 30290605
TI  - Prognostic role of platelet to lymphocyte ratio in prostate cancer: A meta
      analysis.
AB  - BACKGROUND: Recently, the prognostic value of the platelet-to-lymphocyte ratio
      (PLR) has been identified in multiple cancers. However, the prognostic
      significance of the PLR in prostate cancer (PCa) remains conflicting. We
      therefore searched relevant studies and conducted a meta-analysis. METHODS:
      Papers from the databases of PubMed, Web of Science, and the Cochrane Library
      were retrieved. Six studies comprising 1324 patients were included. RESULTS: The
      pooled analysis demonstrated that an elevated PLR predicted poor overall survival
      (OS; HR = 1.85, 95% CI = 1.51-2.25, P < .001) and disease-free survival (DFS; HR
      = 1.4, 95% CI = 1.1-1.79, P = .007). Subgroup analyses showed that the PLR
      remained a significant prognostic factor for OS irrespective of ethnicity, tumor
      stage, or cut-off value. The PLR was an indicator of poor DFS in Asian patients,
      but not in Caucasian patients. No significant publication bias was detected.
      CONCLUSION: This meta-analysis showed that a high PLR was correlated with poor
      DFS and OS in patients with prostate cancer. Due to this meta-analysis being
      derived from a few studies, the results should be validated in clinical practice.

PMID- 30290607
TI  - Winged scapula caused by dorsal scapular neuropathy combined with suprascapular
      neuropathy: A case report.
AB  - RATIONALE: Scapular winging is caused by neuromuscular dysfunction of shoulder
      stabilizer muscles. Clinically, a winged scapula can be easily diagnosed by
      typical physical findings. We report a case of atypical winged scapula caused by
      dorsal scapular neuropathy combined with suprascapular neuropathy, which has
      rarely been reported. PATIENT CONCERNS: A 25-year-old right-handed male was
      admitted to the clinic due to right arm weakness for 1 year. On physical
      examination, right winged scapula with medially rotated inferior angle was
      observed on flexion. DIAGNOSES: Under the diagnostic impression of a winged
      scapula due to long thoracic nerve injury based on physical examination,
      electrodiagnostic study was performed. However, the results showed right dorsal
      scapular neuropathy combined with suprascapular neuropathy. INTERVENTIONS: Neck
      and right shoulder MRI were also performed to rule out other causes of winged
      scapula, but these showed only a partial thickness tear of the rotator cuff
      tendon. The patient received rehabilitation. OUTCOMES: The symptoms have not
      improved. LESSONS: In this case, combined suprascapular neuropathy might
      contribute to scapular winging and can confuse the diagnosis of winged scapula
      based on physical findings. This is the first report that indicates suprascapular
      neuropathy as a contributing factor of scapular winging.

PMID- 30290606
TI  - Phosphaturic mesenchymal tumor and related wound problem.
AB  - INTRODUCTION: Phosphaturic mesenchymal tumor mixed connective tissue type
      (PMT/MCT) is the most common type (up to 90%) of phosphaturic mesenchymal tumor
      (PMT), a rare clinicopathologic entity. Besides overproduction of fibroblast
      growth factor 23 (FGF23), there is a big variation of immunohistochemical
      characteristic across types of PMT, which makes it difficult to obtain an early
      diagnosis of PMT/MCT. As a benign tumor, PMT/MCT usually happens in subcutaneous
      tissues and leads to nonhealing of wound. A complete excision of PMT/MCT
      facilitates wound healing. CONCLUSIONS: Review of the existing evidence indicates
      that early diagnosis of PMT/MCT is critically important when treating PMT/MCT
      wound. Hence standardization of early diagnosis for PMT/MCT is mandated.

PMID- 30290608
TI  - Everolimus-induced pulmonary toxicity: Findings on 18F-FDG PET/CT imaging.
AB  - The everolimus-exemestane combination is indicated in advanced breast cancer
      treatment and usually well tolerated. The objective of the study was to determine
      the frequency of everolimus lung side effects and investigate their imaging
      characteristics on positron emission tomography with 18F-fluoro-deoxy-glucose
      combined with computerized tomography (F-FDG PET/CT).Our single-center
      retrospective descriptive study systematically included all patients with
      metastatic breast cancer treated by this combination (n = 29 representing 57 F
      FDG PET/CT). Number of segments involved was quantified. Maximum standardized
      uptake value (SUVmax), average standardized uptake value (SUVmean), metabolic
      target volume (MTV), and total lesion glycolysis (TLG) were measured. Severe
      pneumopathy was studied by subgroup analysis.Pleuroparenchymal anomalies rate
      detected on F-FDG PET/CT was 62%. Alveolar-interstitial lesions were mainly
      observed (89%) and affected 2.8 segments (0.5-11.5) with a median of 2 segments.
      S7 and S10 were the most involved segments with SUVmax 3.9 (1.3-8.8) and SUVmean
      2.2 (0.7-4.9). Statistically significant difference (P = .02) was found with
      number of segment involved to characterize severe pneumopathy (average of 6.3
      segments [2.5-11.5] vs 1.9 segments [0.5-8] for interstitial lung disease) but
      not with SUVmax, SUVmean, MTV, TLG (P = .14, 0.22, 0.22, and 0.17,
      respectively).The F-FDG PET/CT could highlight pulmonary everolimus side effects,
      with a typical imaging pattern: alveolar-interstitial opacities associated with
      moderate uptake, more or less extensive, mainly affecting the lower lobes.
      Rarely, a pseudotumoral aspect may be detected, corresponding to a pitfall. MTV
      or TLG showed a tendency to differentiate severe pneumopathy vs interstitial lung
      disease but no statistically significant differences was observed contrarily to
      the number of segments involved. Further studies are necessary to determine if
      the F-FDG PET/CT could early predict adverse effects of mTOR inhibitors.

PMID- 30290609
TI  - ICAM-1 gene rs5498 polymorphism decreases the risk of coronary artery disease.
AB  - BACKGROUND: Many studies investigated the association between intercellular
      adhesion molecule 1 (ICAM-1) gene rs5498 polymorphism and the risk of coronary
      artery disease (CAD). However, the results were inconsistent. METHODS: To clarify
      convincing association, we conducted a comprehensive meta-analysis by searching
      in PubMed, Embase, Web of sciences, Sciences citation index, Google scholar,
      Cochrane Library, and the CNKI databases. Pooled odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated. RESULTS: A total of 29 case-control
      studies with 5,494 cases and 6,364 controls for rs5498 polymorphism were
      included. The studied populations of this meta-analysis included Caucasians and
      Asians. Meta-analysis showed that rs5498 polymorphism was associated with the
      decreased risk of CAD. Stratification analysis of ethnicity found that rs5498
      polymorphism decreased the risk of CAD among Caucasians, but not among Asians.
      Stratification by type of CAD revealed that ICAM-1 gene rs5498 polymorphism was
      also correlated with the decreased risk of myocardial infarction (MI).
      CONCLUSION: In conclusion, this meta-analysis indicates that ICAM-1 gene rs5498
      polymorphism decreases the risk of CAD.

PMID- 30290610
TI  - One case report of giant atypical leiomyoma of the ovary.
AB  - RATIONALE: Ovarian leiomyoma is a rare ovarian tumor that occurs in 20-65 year
      old women, and is mostly misdiagnosed as malignant tumor. In most reports on this
      type of tumor, ovarian myoma has a benign histology. Herein,we describe a case of
      ovarian atypical leiomyoma. PATIENT CONCERNS: The patient is a 58-year-old woman.
      At the age of 40 years old, the patient underwent hysterectomy due to
      "hysteromyoma" and secondary anemia. The patient was admitted to our hospital due
      to palpation of lower abdominal mass and abdominal distention. DIAGNOSES: A mass
      was revealed at the left uterine appendage by pelvic ultrasound and CT.Pathology
      and immunohistochemistry confirmed the diagnosis of the left ovarian atypical
      leiomyoma. INTERVENTIONS: Pelvic cavity resection and right adnexectomy were
      performed during laparotomy for the patient. OUTCOMES: Without radiotherapy or
      chemotherapy, there were no signs of tumor recurrence in a 9-month follow-up
      period. LESSONS: When a solid mass appears in ovarian tissues, ovarian leiomyoma
      should be considered. Patients with this type of tumor are mostly asymptomatic.
      Preoperative diagnosis was difficult, intraoperative frozen section would be
      helpful for determining the scope of the surgery, and the correct diagnosis was
      made by identifying the properties of smooth muscles through postoperative
      pathology and immunohistochemistry.

PMID- 30290611
TI  - Effect of perioperative oral management on the prevention of surgical site
      infection after colorectal cancer surgery: A multicenter retrospective analysis
      of 698 patients via analysis of covariance using propensity score.
AB  - Surgical site infection (SSI) is 1 of the frequent postoperative complications
      after colorectal cancer surgery. Oral health care has been reported to reduce the
      risk of SSI or postoperative pneumonia in oral, esophageal, and lung cancer
      surgeries. The purpose of the study was to investigate the preventive effect of
      perioperative oral management on the development of SSI after a major colorectal
      cancer surgery.The medical records of 698 patients who underwent colorectal
      cancer surgery at 2 hospitals in Japan were reviewed. Among these patients, 563
      patients received perioperative oral management (oral management group) and 135
      did not (control group). Various demographic, cancer-related, and treatment
      related variables including perioperative oral management intervention and the
      occurrence of SSI were investigated. The relationship between each variable and
      the occurrence of SSI was examined via univariate and multivariate analyses using
      Fisher exact test, 1-way analysis of variance (ANOVA), and logistic regression.
      The occurrence of SSI in the 2 groups was evaluated via logistic regression using
      propensity score as a covariate. The difference in mean postoperative hospital
      stay between the oral management and control groups was analyzed using Student's
      t test.SSI occurred in 68 (9.7%) of the 698 patients. Multivariate analysis
      showed that operation time, blood loss, and perioperative oral management were
      significantly correlated with the development of SSI. However, after the
      propensity score analysis, not receiving perioperative oral management also
      became a significant risk factor for SSI. The odds ratio of the oral management
      group was 0.484 (P = .014; 95% confidence interval: 0.272-0.862). Mean
      postoperative hospital stay was significantly shorter in the oral management
      group than in the control group.Perioperative oral management reduces the risk of
      SSI after colorectal cancer surgery and shortens postoperative hospital stay.

PMID- 30290612
TI  - Synchronous hepatocellular carcinoma and lymphoepithelioma-like carcinoma arising
      from 2 different sites of the liver: A case report.
AB  - RATIONALE: Most cases of primary liver cancer involve hepatocellular carcinoma
      (HCC). Lymphoepithelioma-like carcinoma (LELC) is defined as a tumor composed of
      undifferentiated epithelial cells with a prominent lymphoid infiltrate, which is
      rarely reported. Lymphoepithelioma-like HCC (LEL-HCC) is an uncommon variant of
      HCC, having an unclear process of development. Here, we report the first case
      involving simultaneous HCC and LEL-HCC. PATIENT CONCERNS: A 77-year-old female
      was accidentally found to have a hypoechoic hepatic nodule via an abdominal
      ultrasound during a health examination. Abdominal computed tomography scan
      revealed 2 hepatic nodules with arterial phase enhancement and washout in the
      late phase. DIAGNOSES: We diagnosed the case with 2 distinct liver nodules, HCC
      and LEL-HCC. INTERVENTIONS: With suspicion of HCC, tumor resection (liver
      segments 4 and 5) was then performed. Histopathological examination of tumor 1
      showed a moderately differentiated HCC and tumor 2 demonstrated a LEL-HCC.
      Immunohistochemically, the cells of tumor 2 were immunoreactive for cytokeratin
      (CK), CK7, and CK19. Epstein-Barr virus encoding small RNA (EBER) in situ
      hybridization results were negative. OUTCOMES: Six months after resection,
      intrahepatic tumor recurrence was noted. Radiofrequency ablation was conducted.
      LESSONS: This is an interesting case providing circumstantial evidence of
      simultaneous development of HCC and LEL-HCC in distinct nodules of the liver with
      a background of chronic hepatitis B virus infection.

PMID- 30290613
TI  - Splenic cystic lymphangiomatosis in association with omental varices and portal
      hypertension: A case report.
AB  - RATIONAL: Lymphangiomatosis is rare and benign, and slowly proliferating
      lymphatic vessels of unknown etiology and visceral lymphangiomatosis involving
      the spleen is rare. Since lymphangiomatosis may be asymptomatic or present as a
      sense of fullness, splenic cystic lymphangiomatosis is a disease of little
      concern. PATIENT CONCERNS: A 34-year-old woman suffering from progressive
      epigastric fullness after oral intake for two weeks. DIAGNOSES: Physical
      examination showed a palpable mass which was more than 10 cm in size over the
      left hypochondrium. An abdominal computed tomography disclosed marked
      splenomegaly with multiple cystic lesions in the spleen, causing external
      compression with right-sided deviation of the adjacent organs and varices in the
      upper abdomen. Esophagogastroduodenoscopy revealed portal hypertensive
      gastropathy. INTERVENTIONS: Conventional total splenectomy was performed in this
      patient because of an enlarged spleen and unknown etiology, preoperatively. Upon
      surgery, splenomegaly with polycystic content and varicose vessels over the
      omentum were noted. Autologous spleen transplantation was not performed because
      of limited orthotopic and vascularized spleen. OUTCOMES: The patient is doing
      well 18 months after splenectomy. LESSONS: This was a rare case presenting with
      splenic cystic lymphangiomatosis in association with omental varices and portal
      hypertension. Splenic cystic lymphangiomatosis should be considered in the
      differential diagnosis of patients with a palpable painless mass over the left
      hypochondrium.

PMID- 30290614
TI  - Herbal medicine Yukgunja-tang for functional dyspepsia protocol for a systematic
      review of randomized controlled trials.
AB  - BACKGROUND: Functional dyspepsia (FD) is a common functional gastrointestinal
      disorder characterized by recurrent dyspeptic symptoms. Yukgunja-tang (YGT) is a
      traditional herbal formula that has been used for treating FD. This systematic
      review protocol aims to provide a guideline for investigating the efficacy and
      safety of YGT in the treatment of FD. METHODS: The following databases will be
      searched from their inception until July 2018: Medline (via PubMed), EMBASE, the
      Cochrane Central Register of Controlled Trials (CENTRAL), Allied and
      Complementary Medicine Database (AMED), KoreaMed, National Digital Science
      Library (NDSL), Korean Medical Database (KMbase), Oriental Medicine Advanced
      Searching Integrated System (OASIS), Korean Studies information Service System
      (KISS), China National Knowledge Infrastructure Database (CNKI), and Citation
      Information by Nii (CiNii). Randomized controlled trials (RCTs) that used YGT or
      modified YGT for treating FD will be included. The control groups in these RCTs
      will include placebo, no-treatment waiting, and conventional western medicine
      groups. Trials testing YGT as an adjunct to western medicine for synergistic
      effect will also be included. The main outcome will be the total clinical
      efficacy rate. Data extraction and risk of bias assessment will be performed by
      two independent assessors. RevMan V.5.3 will be used for data analysis. RESULTS:
      This study will provide a high-quality synthesis of current evidence of YGT for
      FD from several aspects including dyspepsia-related symptoms, quality of life and
      adverse events. CONCLUSION: The conclusion of our systematic review will provide
      evidence to judge whether YGT is an effective intervention for patient with FD.
      ETHICS AND DISSEMINATION: The protocol does not need ethics approval because
      identifying information of the participants will not be revealed. The systematic
      review will be published in a peer-reviewed journal and disseminated
      electronically and in print. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018090139.

PMID- 30290615
TI  - Early post-operative cognitive dysfunction after closed-loop versus manual target
      controlled-infusion of propofol and remifentanil in patients undergoing elective
      major non-cardiac surgery: Protocol of the randomized controlled single-blind
      POCD-ELA trial.
AB  - INTRODUCTION: Post-operative cognitive dysfunction (POCD) is frequent in patients
      older than 60 years undergoing major non-cardiac surgery, and increases both
      morbidity and mortality. Anesthetic drugs may exert neurotoxic effects and
      contribute to the genesis of POCD. The hypothesis of the POCD-ELA trial was that
      closed-loop target-controlled infusion of propofol and remifentanil could reduce
      the occurrence of POCD by decreasing the risk of excessive depth of anesthesia
      and the dose of anesthetic drugs. METHODS AND ANALYSIS: We designed a single
      center, single-blind, randomized, controlled, parallel trial and aim to include
      204 patients aged >60 years undergoing elective major non-cardiac surgery.
      Patients will be randomized to receive closed-loop versus manual target
      controlled infusion of propofol and remifentanil guided by bispectral index
      monitoring. Cognitive assessment will be performed the day before surgery
      (baseline) and within 72 hours after surgery, using a battery of validated
      neuropsychological tests. The primary outcome is the incidence of POCD within 72
      hours after surgery. POCD is defined as a Z-score value > 1.96 for at least 2
      different tests or a Z-score composite value >1.96. The calculation of the Z
      score is based on data from an age-matched control population who did not undergo
      surgery or general anesthesia. ETHICS AND DISSEMINATION: This study was approved
      by the Ethics Committee (Comite de Protection des Personnes Est-II) and
      authorized by the French Health Products Agency (Agence Nationale de Securite des
      Medicaments, Saint-Denis, France). The University Hospital of Besancon is the
      trial sponsor and the holder of all data and publication rights. Results of the
      study will be submitted for publication in a peer-review international medical
      journal and for presentation in abstract (oral or poster) in international peer
      reviewed congresses. REGISTRATION: The trial is registered with
      ClinicalTrials.gov (Identifier: NCT02841423, principal investigator: Prof
      Emmanuel Samain, date of registration: July 22, 2016). Last amendment of
      protocol: version 8.0 April 2018.

PMID- 30290616
TI  - Efficacy and safety of PDE5 inhibitors in the treatment of diabetes mellitus
      erectile dysfunction: Protocol for a systematic review.
AB  - INTRODUCTION: Diabetes mellitus erectile dysfunction (DMED) is a common
      complication of long-term hyperglycemia. With the increasing of diabetic
      patients, the number of DMED patients is gradually growing up, which has a
      serious impact on the quality of life of patients. PDE5 inhibitors have good
      clinical efficacy in DMED patients. This study is designed to evaluate the
      efficacy and safety of PDE5 inhibitors in DMED patients. METHODS AND ANALYSIS: We
      will systematically search all randomized controlled trials (RCTs) by electronic
      and manual search. Electronic retrieval of the database includes Pubmed, EMBASE,
      The Cochrane Library, the Chinese BioMedical Literature Database, the China
      National Knowledge Infrastructure (CNKI), the China Science and Technology
      Journal database (VIP) and the Wanfang database. Manual search will retrieve gray
      literature, including dissertations, ongoing experiments, grey literature,
      conference and unpublished documents. We use the IIEF-5 scale as the primary
      outcome of DMED. We also need to pay attention to the following outcomes: the
      sexual satisfaction of patients and their partners, like IIEF Q3 Q4; SEP 2, 3;
      GAQ. More importantly, the adverse reactions of patients during medication will
      also be taken seriously. Two reviewers will independently read the articles,
      extract the data information, and give the assessment of risk of bias. Data
      analysis will be used the special software like RevMan (version 5.3.5), ENDNOTE
      X7 and STATA 13. RESULTS: This study will provide a comprehensive assessment
      based on current evidence of PDE5 inhibitors for DMED, especially its impacts on
      International Index of Erectile Function, the sexual satisfaction of patients and
      their partners and safety. ETHICS AND DISSEMINATION: This systematic review will
      evaluate the efficacy and safety of PDE5 inhibitors on DMED. This review does not
      require ethical approval and will be reported in a peer-reviewed journal. TRIAL
      REGISTRATION NUMBER: PROSPERO CRD42018095185.

PMID- 30290617
TI  - The association of polymorphisms in promoter region of MMP2 and MMP9 with
      recurrent spontaneous abortion risk in Chinese population.
AB  - This study aimed to reveal the genetic association between polymorphisms in
      promoter region of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase
      9 (MMP9) and the risk of recurrent spontaneous abortion (RSA) in Chinese
      population.A total of 129 RSA patients and 116 relative controls were selected
      and the genotyping of polymorphism was conducted by polymerase chain reaction
      with sequencing. Genotype distribution of polymorphism in the control group was
      tested the status of Hardy-Weinberg equilibrium and then, genotype frequencies
      were compared between the case and control groups by chi-squared test. Odds ratio
      (OR) with the corresponding 95% confidence interval (95% CI) was computed to
      express the risk of RSA caused by polymorphism. Moreover, the linkage
      disequilibrium of polymorphisms in MMP2 was analyzed by Haploview software.CT
      genotype and T allele of rs243865 in MMP2 were significantly associated with the
      increased susceptibility to RSA in Chinese population (CT vs. CC: OR = 1.926, 95%
      CI = 1.101-3.368; T vs. C: OR = 1.751, 95% CI = 1.146-2.676). Similarly, CT
      genotype carriers of rs3918242 in MMP9 were obviously more in RSA patients than
      that of the controls (P = .037), which indicated it was associated with the risk
      of RSA occurrence (OR = 1.760, 95% CI = 1.034-2.995). So was T allele in RSA
      development (OR = 1.595, 95% CI = 1.061-2.398). Haplotypes C-T and T-C were also
      the risk factors of RSA (OR = 1.673, 95% CI = 1.103-2.536; OR = 2.171, 95% CI =
      1.372-2.436).MMP2 rs243865 and MMP9 rs3918242 polymorphisms are significantly
      associated with the risk of RSA in Chinese population.

PMID- 30290618
TI  - Sex hormone therapy's effect on dry eye syndrome in postmenopausal women: A meta
      analysis of randomized controlled trials.
AB  - THE PURPOSE OF THE STUDY T: o assess the efficacy of sex hormone therapy in the
      treatment of dry eye syndrome in postmenopausal women.The following electronic
      databases were searched without language restrictions: PubMed, Embase, Cochrane,
      and the Chinese Biomedical Database. Two reviewers collected all the literature,
      which was searched for relevance in English and Chinese from January 1990 to July
      2017. Both of the reviewers screened documents independently, identifying the
      studies that met the inclusion criteria. Then, the included studies were
      evaluated, and the data were extracted and conversed dependently. Finally, Review
      Manager 5.3 (offered by the Cochrane collaboration) was used to complete the meta
      analysis. An integrated mean difference (MD) with its corresponding 95%
      confidence interval (CI) was calculated.A total of 358 patients with dry eye were
      enrolled in 7 randomized controlled trials (RCTs). We observed statistically
      significant improvements in the Schirmer's test scores (MD, 2.06; 95% CI, 0.74
      4.46; I = 97%; P = .006) after sex hormone treatment. However, the scores for
      tear breakup time (TBUT) (MD, 1.28; 95% CI, -1.03 to 4.68; I = 99%; P = .21) and
      the ocular comfort index (OCI) (MD, -1.12; 95% CI, -4.42 to 1.98; I = 95%; P =
      .48) were not improved.This meta-analysis of 7 RCTs suggests that sex hormone
      therapy may be associated with better Schirmer's test scores. However, no
      significant differences were detected in the TBUT and OCI test scores.
      Consequently, sex hormone therapy has a potentially useful role in the effective
      management of postmenopausal women with dry eye syndrome.

PMID- 30290619
TI  - Prognostic value of transcranial facial nerve motor-evoked potentials in
      predicting facial nerve function following cerebellopontine angle tumorectomy.
AB  - Facial nerve paralysis is a common complication following cerebellopontine angle
      (CPA) surgery. This study investigated the prognostic value of facial nerve motor
      evoked potentials (FNMEPs) elicited by transcranial electrical stimulation for
      facial nerve outcome after CPA tumorectomy.A total of 95 patients were enrolled
      in this study between January 2014 and January 2016. All these patients underwent
      CPA tumorectomy (unilateral, n = 95; bilateral, n = 1). Intraoperative FNMEP
      elicited by transcranial electrical stimulation was recorded. The short- and long
      term postoperative facial nerve functions were evaluated according to the House
      Brackmann (HB) scale. The correlation between perioperative changes in the FNMEP
      stimulus threshold (delta FNMEP = postoperative stimulus threshold level
      preoperative stimulus threshold level) and postoperative facial nerve functions
      were analyzed.On the first day postoperatively, the facial nerve function was HB
      grade I in 67, grade II in 17, grade III in 7, and grade IV in 5 facial nerves.
      One year postoperatively, the facial nerve function was grade I in 80, grade II
      in 11, grade III in 3, and grade IV in 2 facial nerves. The delta FNMEP was
      significantly correlated with the short- and long-term facial nerve function;
      receiver operating characteristic (ROC) curves yielded a cut-off delta FNMEP
      value of 30 V (sensitivity, 91.3%; specificity, 98.6%) and 75 V (sensitivity,
      100%; specificity, 98.8%) for predicting short- and long-term facial nerve
      function damage, respectively.FNMEP elicited by transcranial electrical
      stimulation is an effective and safe approach for predicting facial nerve
      function in CPA tumorectomy. A high delta FNMEP is a potential indicator for the
      prediction of postoperative facial nerve damage.

PMID- 30290620
TI  - 99mTc-MIBI single photon emission computed tomography/computed tomography for the
      incidental detection of rare parathyroid carcinoma.
AB  - This study aimed to evaluate the characteristics of parathyroid carcinoma and to
      validate the diagnostic value of Tc-methoxyisobutylisonitrile (MIBI) single
      photon emission computed tomography/x-ray computed tomography (SPECT/CT) for
      differentiating between parathyroid carcinoma and hyperparathyroidism. Four
      consecutive patients with suspected primary hyperparathyroidism were enrolled in
      this study and underwent Tc-MIBI SPECT/CT, ultrasonography, enhanced CT, and MRI.
      Serum parathyroid hormone (PTH) and calcium were measured. All primary and
      recurrent lesions showed high focal uptake on Tc-MIBI image, whereas metastatic
      lymph nodes gave false negative results. The serum PTH was 165.14 +/- 90.26
      pmol/L, which declined rapidly after surgery. One patient with a persistently
      high PTH (147.5 pmol/L) after surgery presented with multiple lymphadenopathy in
      the neck. Higher expression of chromogranin A (CgA) further confirmed parathyroid
      carcinoma as a rare endocrine tumor. Parathyroid carcinoma is thus usually
      diagnosed incidentally based on nonspecific multiorgan symptoms of hypercalcemia
      and hyperparathyroidism. Tc-MIBI SPECT/CT may help to localize the parathyroid
      carcinoma, while MRI is valuable for detecting metastasis. Serum PTH and CgA
      serve as circulating biomarkers in parathyroid carcinoma, and raised levels of
      PTH and CgA together with locoregional lymphadenopathy may indicate parathyroid
      carcinoma. Further studies are needed.

PMID- 30290622
TI  - Application of lower limb nerve block combined with slow induction of light
      general anesthesia and tracheal induction in elderly hip surgery.
AB  - BACKGROUND: This study aims to evaluate the effectiveness and safety of lower
      limb nerve block combined with slow induction of light general anesthesia and
      tracheal intubation in hip surgery in the elderly. METHODS: Thirty elderly
      patients who underwent hip surgery under the lower limb nerve block were randomly
      divided into 2 groups: slow induction of light general anesthesia and tracheal
      intubation group (group M), and laryngeal mask light general anesthesia group
      (group H). After undergoing total intravenous anesthesia without muscle
      relaxants, all patients received sciatic nerve, lumbar plexus, and paravertebral
      nerve blocks. The hemodynamic situations, dosage of anesthetics, time for
      awakening and extubation (or laryngeal mask removal), and incidence of
      respiratory adverse reactions in the induction period were recorded. RESULTS:
      Compared with baseline levels, the difference in mean arterial pressure (MAP)
      value at each time point after intubation/laryngeal mask removal in both groups
      was not statistically significant (P > .05). Furthermore, the time for awakening
      and extubation/laryngeal mask removal, and anesthetic dosage were significantly
      decreased in group M, when compared with group H (P < .05). For the incidence of
      adverse reactions, the incidence of poor sealing and hypoxia was significantly
      lower in group M than in group H (P < .05), and the incidence of sore throat was
      significantly lower in group H than in group M (P < .05). CONCLUSION: Lower limb
      nerve block combined with slow induction of light general anesthesia and tracheal
      intubation was associated with smaller anesthetic dosage, and shorter duration of
      anesthesia induction and extubation/laryngeal mask after surgery.

PMID- 30290621
TI  - Genetic polymorphisms of the drug-metabolizing enzyme CYP2J2 in a Tibetan
      population.
AB  - As an important metabolic enzyme, it is necessary to investigate the genetic
      polymorphisms of CYP2J2 among healthy Tibetan individuals. Genetic polymorphisms
      of CYP2J2 could affect enzyme activity and lead to differences among individual
      responses to drugs.We sequenced the whole gene of CYP2J2 in 100 unrelated,
      healthy Tibetan volunteers from the Tibet Autonomous Region and screened for
      genetic variants in the promoters, introns, exons, and the 3'-UTR regions.We
      detected 4 novel genetic polymorphisms of the CYP2J2 gene. The allelic
      frequencies of CYP2D6*1 and *7 were 0.955 and 0.045, respectively. CYP2D6*1/*7
      decreased the activity of CYP2J2 and was expressed in 9% of the sample
      population.Our results provided basic data about CYP2J2 polymorphisms in a
      Tibetan population, suggested that the enzymatic activities of CYP2J2 might be
      different within the ethnic group, and offered a theoretical basis for
      individualized medical treatment and drug genomics studies.

PMID- 30290623
TI  - Comparison of transcatheter closure, mini-invasive closure, and open-heart
      surgical repair for treatment of perimembranous ventricular septal defects in
      children: A PRISMA-compliant network meta-analysis of randomized and
      observational studies.
AB  - OBJECTIVE: Our study was aimed to comprehensively compare the relative efficacy,
      safety, and the cost of transcatheter closure, mini-invasive closure, and open
      heart surgical repair to treat perimembranous ventricular septal defects (pmVSDs)
      in children using network meta-analysis method. METHODS: Five databases were
      systematically searched including Chinese Biomedical Literature Database, China
      National Knowledge Infrastructure, PubMed, EMBASE.com, and the Cochrane Central
      Register of Controlled Trials from the starting date of each database to February
      2017. Tools for assessing the risk of bias in nonrandomized studies of
      interventions (ROBINS-I) were used to evaluate the risk of bias in observational
      studies and Cochrane Handbook version 5.1.0 was used for randomized controlled
      trials (RCTs). Data were analyzed using R-3.4.0 software and Review Manager 5.2.
      RESULTS: Three RCTs and 24 observational studies were included in our study.
      Network meta-analysis result demonstrated that transcatheter closure was the most
      effective treatment in terms of operative time [standardized mean difference
      (SMD) = -2.02, 95% confidence interval (CI): -3.92 to -0.12], major complications
      [odds ratio (OR) = 0.52, 95% CI = 0.30-0.91], ICU stay (SMD = -1.11, 95% CI = 
      2.13 to -0.08), and hospital stay (SMD = -1.81, 95% CI = -2.24 to -1.39).
      However, open-heart surgical repair showed a higher success rate of the procedure
      than transcatheter closure (OR = 0.36, 95% CI = 0.17-0.77).Statistical analysis
      result demonstrated that transcatheter closure had the best potential to lessen
      major complications, ICU stay, hospital stay, operative time, and significant
      residual shunt. CONCLUSIONS: Transcatheter closure has more benefit than mini
      invasive closure and open-heart surgical repair to treat pmVSDs.

PMID- 30290624
TI  - Eculizumab in a pregnant patient with laboratory onset of catastrophic
      antiphospholipid syndrome: A case report.
AB  - RATIONALE: Hypercoagulability and pregnancy morbidity are hallmarks of the
      antiphospholipid syndrome (APS). Catastrophic antiphospholipid syndrome (CAPS) is
      a potentially life-threatening omplication of APS, with widespread acute
      thrombotic microangiopathy (TMA) that can be precipitated by pregnancy and
      delivery and result in multiorgan damage. Unrestrained activation of the
      complement cascade is involved, favoring endothelial activation, tissue factor
      expression by leukocytes, and platelet aggregation. The complement block, which
      interrupts this amplification cycle, could prevent CAPS in patients with early
      TMA who face precipitating events. PATIENT CONCERNS: We present a nulliparous
      pregnant woman with APS at the 30 week of gestation who has developed
      thrombocytopenia, intravascular hemolysis, elevated creatinine, proteinuria, and
      hematuria. DIAGNOSES: These featurs were compatible with the diagnosis of CAPS.
      Consensually, serum C3 protein levels were rapidly decreasing, reflecting
      complement consumption. INTERVENTIONS: She was treated with eculizumab, a
      humanized monoclonal antibody against C5 that prevents the formation of the
      complement membrane attack complex. OUTCOMES: Laboratory parameters improved and
      the patient did not develop thrombosis or detectable organ/tissue damage. The
      patient safely delivered by cesarean section at week 32 of gestation a healthy
      1640 g male infant. After 5 days, she received additional eculizumab, with
      complete resolution of the clinical condition. Low complement activity was
      detectable in the infant blood for a week after delivery. No infectious
      complication occurred. LESSONS: Inhibition of the terminal complement activation
      is safe and might be effective in patients with APS developing early TMA,
      enabling safe delivery and preventing thrombotic events both in the mother and in
      the newborn.

PMID- 30290625
TI  - Bidirectionality of the dentato-rubro-thalamo-cortical tract allows concurrent
      hypoperfusion in ipsilateral cerebellum and contralateral cerebral hemisphere: A
      case report.
AB  - RATIONALE: The brain circulation of the dentato-rubro-thalamo-cortical tract
      (DRTT) has been reported for decade, but is rarely observed using nuclear
      medicine imaging tools, to analyze a patient with midbrain hemiatrophy syndrome.
      We present a case that revealed notable interruption in the middle of the DRTT.
      Finding out whether the superior cerebellar peduncle of the midbrain was injured
      was a decisive element for developing bidirectional effect of DRTT. PATIENT
      CONCERNS: A 34-year-old right-handed female presented with progressive weakness
      and bradykinesia in the left-sided limbs for about 6 months. She had difficulty
      with hand dexterity for activities of daily life and general tasks. She reported
      poor balance during walking and sitting. Muscle strength was 3 in the left hand
      and 4 in the foot due to atrophy of left limbs. The circumference of 10 cm
      proximally/distally from the lateral epicondyle of the humerus was 25.7/23.8 cm
      at right and 24.2/20.8 cm at left in the upper limbs, and 15 cm
      proximally/distally from the lateral joint space was 42.1/35.0 cm at right and
      43/30.8 cm at left in the lower limbs. The brain magnetic resonance imaging study
      revealed a small-sized right midbrain. DIAGNOSIS: Based on the distinct features
      of limbs atrophy and the locations of the lesions on the magnetic resonance (MR)
      imaging, the patient was diagnosed with midbrain hemiatrophy syndrome.
      INTERVENTIONS: The patient was only willing to accept physical and occupational
      training programs at our outpatient clinic. OUTCOMES: We utilized serial anatomic
      and functional neuroimaging of the brain to survey the neurologic deficit. Brain
      perfusion single-photon emission computed tomography (SPECT) showed hypoperfusion
      over the left fronto-parietal regions, left anterior temporal region, and left
      occipital region, and also the left striatum and right cerebellum. Symptoms were
      gradually recovered with rehabilitation, and he was transferred to a
      rehabilitation facility on hospital day 40. LESSONS: This is the first report to
      demonstrate concurrent hypoperfusion of ipsilateral cerebellum and contralateral
      cerebral hemisphere observed on SPECT images in a case of midbrain hemiatrophy
      syndrome. In our case, with midbrain hemiatrophy syndrome could be explained as
      mutual direction effect of DRTT.

PMID- 30290626
TI  - Lethal neonatal mitochondrial phenotype caused by a novel polymerase subunit
      gamma mutation: A case report.
AB  - RATIONALE: Polymerase subunit gamma (POLG) is a gene that codes for the catalytic
      subunit of the mitochondrial DNA polymerase, which is involved in the replication
      of mitochondrial DNA. Mutations in these genes are associated with a range of
      clinical syndromes characterized by secondary mtDNA defect including mtDNA
      mutation and mtDNA depletion which may culminate in complete failure of energy
      production (respiratory changes complex 1 defect) as in this case. PATIENT
      CONCERNS: We herein report a full term Saudi female neonate born to
      consanguineous parents, who was noticed immediately after birth to have severe
      hypotonia, poor respiratory effort, and dysmorphic features. She had 3 siblings
      who died with same clinical scenario in neonatal period. DIAGNOSES: Molecular
      genetic testing revealed a novel compound heterozygous mutation of POLG gene
      c.680G>A (p.Arg227Gin) and c.3098C>T (p.Ala1033Val). INTERVENTIONS: The patient
      remained in neonatal intensive care unit with multidisciplinary team management
      and was ventilator dependent until she passed away. OUTCOMES: The detected
      mutation had led to complete failure of energy production (respiratory changes
      complex 1 defect) until she died at the age of 5 months. LESSONS: Mitochondrial
      respiratory chain defect should be considered in patients with severe neonatal
      hypotonia,encephalopathy, and respiratory failure especially in highly
      consanguineous population.

PMID- 30290627
TI  - Comparison of blind intubation via supraglottic airway devices versus standard
      intubation during different airway emergency scenarios in inexperienced hand:
      Randomized, crossover manikin trial.
AB  - BACKGROUND: Securing the airway and enabling adequate oxygenation and ventilation
      is essential during cardiopulmonary resuscitation (CPR). The aim of the study was
      to evaluate the success rate of blind intubation via the I-Gel and the Air-Q
      compared with direct laryngoscopy guided endotracheal intubation by inexperienced
      physician and to measure time to successful intubation. METHODS: The study was
      designed as a randomized, cross-over simulation study. A total of 134 physicians,
      from specialties other than Anesthesia or Emergency Medicine, who considered
      themselves skilled in endotracheal intubation but who have never used any kind of
      supraglottic airway device performed blind intubation via the I-Gel and Air-Q and
      direct laryngoscopy guided endotracheal intubation in 3 randomized scenarios:
      normal airway without chest compression during intubation attempt; normal airway
      with continuous chest compression during intubation attempt; difficult airway
      with continuous chest compression. RESULTS: Scenario A: Success rate with initial
      intubation attempt was 72% for endotracheal intubation, 75% in Air-Q, and 81% in
      I-Gel. Time to endotracheal intubation and ease of intubation was comparable with
      all 3 airway devices used. Scenario B: Success rate with the initial intubation
      attempt was 42% for endotracheal intubation, compared with 75% in Air-Q and 80%
      in I-Gel. Time for endotracheal intubation was significantly prolonged in
      endotracheal intubation (42 seconds, 35-49), compared with Air-Q (21 seconds, 18
      32) and I-Gel (19 seconds, 17-27). Scenario C: The success rate with the initial
      intubation attempt was 23% in endotracheal intubation, compared with 65% in Air-Q
      and 74% in I-Gel. Time to intubation was comparable with both supraglottic airway
      devices (20 vs 22 seconds) but was significantly shorter compared with
      endotracheal intubation (50 seconds, P < .001). CONCLUSIONS: Less to moderately
      experienced providers are able to perform endotracheal intubation in easy airways
      but fail during ongoing chest compressions and simulated difficult airway.
      Consequently, less to moderately experienced providers should refrain from
      endotracheal intubation during ongoing chest compressions during CPR and in
      expected difficult airways. Supraglottic airway devices are reliable alternatives
      and blind intubation through these devices is a valuable airway management
      strategy.

PMID- 30290628
TI  - Musculoskeletal complaints in healthcare personnel in hospital: An
      interdepartmental, cross-sectional comparison.
AB  - The objective of this study is to investigate musculoskeletal complaints (MSCs)
      in healthcare workers (HCWs) in 3 community hospital-based departments [internal
      medicine (IM), general surgery (GS), and emergency department (ED)] and its
      effects on the quality of work life (QWL) of hospital HCW.This prospective cross
      sectional study was performed in the 700-bed community training hospital. All HCW
      staffed in 3 departments (IM, GS, ED) of the hospital were asked to respond to
      items in the study data sheet. Enrolled personnel were inquired about their
      demographic data, work history and schedule, and medical history. The 16-item
      Cornell Musculoskeletal Discomfort Questionnaire (CMDQ) Turkish version was
      applied to evaluate MSC. A total of 216 HCW constituted the study sample and
      demographic characteristics, history, and clinical findings were analyzed.Among
      all, 103 personnel (47.7%) were women (n = 42, 41.1% in physicians, n = 57, 87.6%
      in nurses and n = 4, 8% in other HCW) (P = .000). A total of 173 personnel
      (79.7%) reported MSC in some part of their bodies. Female personnel had MSC
      significantly more commonly than males (chi-square = 40.7, P = .000). Numbers and
      percentages of the personnel with MSC in 3 departments (IM, GS, ED) were 51/61,
      52/65, and 70/90, respectively (P = .67). Total QWL score of those without MSC
      was significantly higher than others (74.7 + -12 vs 63.2 + -15, respectively; t
      test, P = .000). Total frequency score of MSC as elicited via CMDQ was
      significantly higher in those without MSC compared to the others (8.1 + -7.6 vs
      0.1 + -0.6, respectively, t test, P = .000).Female sex, high-income, university
      graduation, being a nurse or a physician, and older age impose risk for HCW in
      hospital with respect to having MSC. Presence of MSC affects QWL negatively.

PMID- 30290629
TI  - Effect of gel seat cushion on chronic low back pain in occupational drivers: A
      double-blind randomized controlled trial.
AB  - BACKGROUND: Low back pain (LBP) is an exceedingly common medical condition that
      results in significant medical and social burden. Sitting for a long period is a
      common aggravating factor for LBP. Although seat cushion is known to promote
      comfort, relieve pressure, and correct posture, its effect on chronic LBP has not
      yet been investigated. This study aimed to evaluate the clinical effect of gel
      seat cushion on chronic LBP in occupational drivers. METHODS: Occupational
      drivers with chronic LBP lasting for >6 months were recruited. Subjects were
      double-blinded, randomly assigned to 2 groups (gel and foam cushion groups), and
      instructed to use the provided cushions while driving. Pain threshold and tissue
      hardness were measured at tender points using a digital algometer. Numeric pain
      intensity scale (NPIS), Roland-Morris Disability Questionnaire (RMDQ), and
      Oswestry Disability Index (ODI) were used to analyze the primary endpoint,
      whereas the Beck Depression Inventory and Short Form-6D were used for the
      secondary endpoint. RESULTS: Of 80 enrolled subjects, 75 (gel cushion group, 40;
      foam cushion group, 35) were included for analysis. Both groups showed
      significant improvement in NPIS and ODI scores following cushion use. Results for
      Beck Depression Inventory and Short Form-6D scores indicated that gel cushion use
      was significantly helpful. Change in NPIS score was significantly greater in the
      gel cushion group than in the foam cushion group. CONCLUSION: Gel cushion use may
      be effective in relieving LBP in occupational drivers seated for a long period
      compared with foam cushion use.

PMID- 30290630
TI  - Curative-intent radiotherapy in patients with oligometastatic lesions from
      colorectal cancer: A single-center study.
AB  - The purpose of the present study was to investigate the efficacy and safety of
      radiotherapy for patients with oligometastases from colorectal cancer (CRC).This
      was a retrospective cross-sectional study. Patients with liver and/or lung
      oligometastatic lesions from CRC treated with curative-intent radiotherapy in
      West China Hospital, Sichuan University, between 2009 and 2013 were included.
      Radiotherapy modality included 3-dimensional conformal radiation therapy (3D
      CRT), intensity-modulated radiation therapy (IMRT), and stereotactic body
      radiation therapy (SBRT); simultaneous chemotherapies along with radiotherapy of
      metastasis were allowed. Overall survival (OS) and progression-free survival
      (PFS) were calculated using the Kaplan-Meier method. Local control (LC) rates,
      toxicities, and factors of prognostic significance were also assessed.A total of
      40 CRC patients with 57 liver and/or lung oligometastatic lesions were included.
      Most of the patients (95%) had received at least 1 line of previous systemic
      chemotherapy. Among them, 19 patients with 26 lesions received 3D-CRT with a
      median dose of 51.5 Gy in 16.1 fractions, 7 patients with 11 lesions received
      IMRT with a median dose of 49.3 Gy in 10.4 fractions, and 14 patients with 20
      lesions received SBRT with a median dose of 56.4 Gy in 6.7 fractions,
      respectively. The median follow-up time was 34 months (range, 9-86 months).
      Median OS and PFS for patients were 30.0 months [95% confidence interval (95%
      CI), 21.3-38.7] and 11.0 months (95% CI, 9-13), respectively. One, 3, and 5
      years' LC rates for metastasis were 63.2%, 24.6%, and 16.9%, respectively. In
      subgroup analysis, patients with metachronous metastases had longer OS (median,
      41.0 months; 95% CI, 33.3-48.7) than patients with synchronous lesions (median,
      17.0 months; 95% CI, 7.4-26.6, P = .001). All patients tolerated the radiation
      treatment well, and there was no treatment-related death. Multivariate analysis
      showed that number of metastasis lesions and simultaneous liver and lung
      metastases were potential survival predictors.The study demonstrated that
      curative radiotherapy might be a tolerable and potential alternative for the
      treatment of patients with liver and/or lung oligometastases from CRC, and
      patients with metachronous lesions might have better survival than those with
      synchronous lesions when treated with curative-intent radiotherapy.

PMID- 30290631
TI  - Magnetic resonance imaging of the fetal brain at 3 Tesla: Preliminary experience
      from a single series.
AB  - To report our preliminary experience with cerebral fetal magnetic resonance
      imaging (MRI) with a 3 Tesla (3T) scanner. We assessed feasibility, time of
      acquisition, and possibility to establish a diagnosis.Fifty-nine pregnant women
      had fetal MRI performed during the third trimester of pregnancy due to clinical
      or sonography concern of a central nervous system anomaly. No fetal or maternal
      sedation was used. The MRI protocol consisted of T2 turbo-spin-echo images in 3
      planes of space. No T1-weighted images were performed. All images were analyzed
      by 2 pediatric neuroradiologists, who evaluated spatial resolution, artifacts,
      time of acquisition, and possibility to establish a diagnosis suspected by
      sonography.Examinations were performed safely for all patients. The images
      required longer time of acquisition (approximately 75 seconds for each plane in
      the space). The specific absorption rate was not exceeded in any fetus. Cerebral
      fetal MRI was normal in 22 cases. The spectrum of diagnostics included isolated
      ventriculomegaly, posterior fossa malformation, corpus callosum malformation,
      gyration anomalies, craniosynostosis, tuberous sclerosis, microcephaly, external
      hydrocephaly, midline arachnoid cyst, cerebral lesions, and persistent
      hyperplastic primitive vitreous.In our series, 3 T MRI of fetal brain was
      feasible and able to establish a diagnosis but required longer time of
      acquisition.

PMID- 30290632
TI  - Long-term follow-up of fibular graft for the reconstruction of bone defects.
AB  - The use of fibular graft for the reconstruction of bone defects has been
      demonstrated to be a reliable method. The aim of this study was to assess the
      clinical outcome of graft union, functional outcome (hypertrophy of the graft
      bones) and complications of both non-vascularized and vascularized grafts.From
      1981 to 2015, 10 patients were treated using non-vascularized fibular graft or
      free vascularized fibular graft. The outcomes were bony union time, graft
      hypertrophy and complications based on radiograph and functional outcomes
      according to the Musculoskeletal Tumor Society (MSTS) score. Mobility of the
      ankle at the donor site was evaluated using the Kofoed ankle score system.This
      study included 10 patients with an average follow-up of 6.8 years. The union rate
      for all patients was 100%. The mean union time was 21.3 weeks for vascularized
      fibular grafts and 30.5 weeks for non-vascularized fibular grafts (P = .310).
      There was a significant difference between the upper limbs and the lower limbs
      regarding hypertrophy of the grafts in 5 patients (P = .003). The mean MSTS score
      in 10 patients was 84% (range 53%-97%). Stress fracture of the graft occurred in
      1 patient. Donor site complications, including valgus deformity and length
      discrepancy, between 2 legs occurred in 2 patients who were under 18 years of age
      at the time of operation (P = .114). The mean Kofoed score was 96.8 (range 88
      100).A greater increase in hypertrophy of grafts was observed with reconstruction
      in the lower limbs. There was no difference in MSTS score between these 2 types
      of grafts. Children were more likely to experience the valgus deformity at the
      donor site after harvesting the fibula. Keeping at least the distal 1/4 of the
      fibula intact during the surgery is a valid means of ensuring ankle stability at
      the donor site, and children should be considered for prophylactic distal
      tibiofibular synostosis creation to prevent the valgus deformity of the ankle at
      the donor site.

PMID- 30290633
TI  - Neck xanthogranuloma mimicking malignancy in a patient with diabetes mellitus: A
      case report and literature review.
AB  - RATIONALE: Xanthogranulomatous inflammation (XGI) is a rare inflammatory process,
      which mostly affects the kidney and gallbladder. It usually simulates an
      aggressive neoplastic process. Occurrences in the neck are extremely rare and
      would usually be associated with a preexisting cyst or glandular tissues. PATIENT
      CONCERNS: A 49-year-old diabetic patient presented with a right painful neck mass
      for a week. The pretreatment computed tomography (CT) imaging with contrast
      demonstrated a huge ill-defined heterogeneous-enhanced lesion abutting
      surrounding musculatures and great vessels. Both fine needle aspiration (FNA) and
      ultrasound-guided core biopsy of the neck mass showed inflammatory cells only.
      DIAGNOSES: Histologic evaluation found granulation tissue with histiocytes and
      occasional Touton giant cells confirming the diagnosis of xanthogranuloma.
      INTERVENTIONS: Open excisional biopsy demonstrated a yellowish mass-like lesion
      with abscess inside. OUTCOMES: The patient recovered from the disease without
      posttreatment comorbidities. LESSONS: This case highlights the need for
      physicians to maintain awareness of this clinical entity and delayed- or
      overtreatment should be avoided in these patients due to preoperative ambiguous
      diagnosis.

PMID- 30290634
TI  - Selection of pancreaticojejunostomy technique after pancreaticoduodenectomy: duct
      to-mucosa anastomosis is not better than invagination anastomosis: A meta
      analysis.
AB  - BACKGROUND: One of the most clinically significant current discussions is the
      optimal pancreaticojejunostomy (PJ) technique for pancreaticoduodenectomy (PD).
      We performed a meta-analysis to compare duct-to-mucosa and invagination
      techniques for pancreatic anastomosis after PD. METHODS: A systematic search of
      PubMed, Embase, Web of Science, the Cochrane Central Library, and
      ClinicalTrials.gov up to June 1, 2018 was performed. Randomized controlled trials
      (RCTs) comparing duct-to-mucosa versus invagination PJ were included. Statistical
      analysis was performed using RevMan 5.3 software. RESULTS: Eight RCTs involving
      1099 patients were included in the meta-analysis. The rate of postoperative
      pancreatic fistula (POPF) was not significantly different between the duct-to
      mucosa PJ (110/547, 20.10%) and invagination PJ (98/552, 17.75%) groups in all 8
      studies (risk ratio, 1.13; 95% CI, 0.89-1.44; P = .31). The subgroup analysis
      using the International Study Group on Pancreatic Fistula criteria showed no
      significant difference in POPF between duct-to-mucosa PJ (97/372, 26.08%) and
      invagination PJ (78/377, 20.68%). No significant difference in clinically
      relevant POPF (CR-POPF) was found between the 2 groups (55/372 vs 40/377, P =
      .38). Additionally, no significant differences in delayed gastric emptying, post
      pancreatectomy hemorrhage, reoperation, operation time, or length of stay were
      found between the 2 groups. The overall morbidity and mortality rates were not
      significantly different between the 2 groups. CONCLUSION: The duct-to-mucosa
      technique seems no better than the invagination technique for pancreatic
      anastomosis after PD in terms of POPF, CR-POPF, and other main complications.
      Further studies on this topic are therefore recommended.

PMID- 30290635
TI  - Acupotomy therapy for lumbar disc herniation: Protocol for a systematic review
      and meta-analysis.
AB  - BACKGROUND: Lumbar disc herniation (LDH) is a clinically common degenerative
      spinal disease that adversely affects patients' quality of life and work ability.
      Although several articles have reported that acupotomy can improve the clinical
      symptoms of LDH, the efficiency of acupotomy has not been scientifically or
      methodically evaluated. The primary objective of this study is to evaluate and
      synthesize evidence on the effectiveness and safety of acupotomy therapy in
      patients with LDH. METHOD: We plan to search eight English and Chinese electronic
      databases, including the Web of Science, Cochrane Library, PubMed, EMBASE,
      SinoMed, Wanfang, China Science and Technology Journal (VIP), and China National
      Knowledge Infrastructure (CNKI) databases, for potentially eligible studies.
      Randomized controlled trials (RCTs) on acupotomy treatment in LDH patients will
      be searched for independently by 2 reviewers in the databases from their
      inception to August 2018. We will combine data from clinically homogenous studies
      in a fixed effect meta-analysis using RevManV.5.3.5, and the evidence level will
      be assessed by using the method for Grading of Recommendations Assessment,
      Development, and Evaluation (GRADE). RESULTS: This systematic review and meta
      analysis will use high-quality evidence-based medicine to assess the efficacy and
      safety of acupotomy therapy in LDH. CONCLUSION: This study protocol will provide
      strong evidence to determine whether acupotomy therapy is an effective and safe
      intervention for patients with LDH.

PMID- 30290636
TI  - Blood homocysteine levels could predict major adverse cardiac events in patients
      with acute coronary syndrome: A STROBE-compliant observational study.
AB  - The Global Registry of Acute Coronary Events (GRACE) risk score independently
      predicts major adverse cardiac events (MACEs) in patients with acute coronary
      syndrome (ACS). This study aims to evaluate whether the level of plasma
      homocysteine in addition to the GRACE score enhances the predictive value for
      MACEs in patients with acute coronary syndrome.A total of 361 patients with ACS
      evaluated at our hospital were included in the study and tested for blood
      homocysteine levels. We recorded 40 (11.1%) instances of MACE during a median
      follow-up of 43.3 months (quartile 40.6-44.4 months), including 29 cases (8.0%)
      of all-cause death and 11 cases (3.1%) of nonfatal myocardial infarction.The
      GRACE score was significantly associated with homocysteine levels, and
      multivariate Cox regression analysis showed that both the GRACE risk score and
      homocysteine content were independent predictors of MACEs (HR 2.63; 95%
      confidence interval (CI) 1.54 to 4.49; P < .001 and 2.27; 1.06 to 4.86; P = .035,
      respectively). Moreover, meta-analysis showed that as the homocysteine level
      increased, the incidence of MACEs also increased (log-rank 8.41; P = .015). GRACE
      scores adjusted by homocysteine level increased the area under the curve (AUC)
      from 0.78 to 0.83 (P = 0.006).Blood homocysteine levels are significantly
      associated with the GRACE risk score, and using both parameters can further
      improve risk stratification in patients with acute coronary syndrome.

PMID- 30290637
TI  - Therapeutic outcome of spinal implant infections caused by Staphylococcus aureus:
      A retrospective observational study.
AB  - Spinal implant infection is a rare but significant complication of spinal fusion
      surgery, and the most common pathogen is Staphylococcus aureus. It is difficult
      to treat due to this pathogen's biofilm-forming ability and antibiotic
      resistance. We evaluated the therapeutic outcome of treatments for S aureus
      spinal implant infections. We retrospectively reviewed all patients with S aureus
      spinal implant infections at 11 tertiary-care hospitals over a 9-year period.
      Parameters predictive of treatment failure and recurrence were analyzed by Cox
      regression. Of the 102 patients with infections, 76 (75%) were caused by
      methicillin-resistant S aureus (MRSA) and 51 (50%) were late-onset infections. In
      all, 83 (81%) patients were managed by debridement, antibiotics, and implant
      retention (DAIR) and 19 (19%) had their implants removed. The median duration of
      all antibiotic therapies was 52 days. During a median follow-up period of 32
      months, treatment failure occurred in 37 (36%) cases. The median time to
      treatment failure was 113 days, being <1 year in 30 (81%) patients. DAIR
      (adjusted hazard ratio [aHR], 6.27; P = .01) and MRSA infection (aHR, 4.07; P =
      .009) were independently associated with treatment failure. Rifampin-based
      combination treatments exhibited independent protective effects on recurrence
      (aHR, 0.23; P = .02). In conclusion, among patients with S aureus spinal implant
      infections, MRSA and DAIR were independent risk factors for treatment failure,
      and these risk factors were present in the majority of patients. In this
      difficult-to-treat population, the overall treatment failure rate was 36%;
      rifampin may improve the outcomes of patients with S aureus spinal implant
      infections.

PMID- 30290638
TI  - Rivaroxaban improves hidden blood loss, blood transfusion rate and reduces
      swelling of the knee joint in knee osteoarthritis patients after total knee
      replacement.
AB  - Osteoarthritis (OA) is the third most common diagnosis made by general
      practitioners in older patients. The purpose of the current study is to
      investigate effects rivaroxaban had on both hidden blood loss and blood
      transfusion rate (BTR) in patients with knee OA (KOA) after going through a total
      knee replacement (TKR).Between the time periods of December 2011 up until January
      2015, a total of 235 patients underwent TKR and were selected to be assigned to
      either the rivaroxaban or nonanticoagulant groups. Coagulation function indexes
      before surgery and following administration of rivaroxaban, total blood loss,
      hidden blood loss, dominant blood loss, blood transfusion volume, hemoglobin
      reduction, degree of postoperative pain (visual analogue scale), the degree of
      knee swelling, and range of motion following surgery were all recorded. Hospital
      for special surgery (HSS) scores offered an objective evaluation for the knee
      joint functions before surgery at the intervals of 2 weeks and after surgery at
      intervals of 3 months, 6 months, 12 months, and 24 months.Patients in the
      rivaroxaban group had shown a higher hidden blood loss, as well as a higher BTR,
      compared to those involved in the nonanticoagulant group. BTR was found to have
      been 49.59% in the rivaroxaban group, and 35.09% for the nonanticoagulant group.
      Patients in the rivaroxaban group had lower degrees of knee swelling than those
      involved in the nonanticoagulant group. There was no deep vein thrombosis (DVT)
      detected in the rivaroxaban group, whereas 5 DVT cases were detected in the
      nonanticoagulant group. In the rivaroxaban group, the HSS scores of the knee
      joint functions were remarkably higher at the 2-week mark in succession to the
      surgery than those involved with the nonanticoagulant group.This overall data
      demonstrated that KOA patients after TKR had presented with a higher hidden blood
      loss, BRT, and lower swelling degrees of the knee joint after being treated by
      the rivaroxaban.

PMID- 30290639
TI  - Role of qSOFA in predicting mortality of pneumonia: A systematic review and meta
      analysis.
AB  - BACKGROUND: The concept of sepsis was redefined recently, and a new screening
      system termed the quick Sequential Organ Failure Assessment (qSOFA) was
      recommended for identifying infected patients at high risk for death. However,
      the predictive value of qSOFA for mortality in patients with pneumonia remains
      unclear. Thus, we performed a meta-analysis with the aim of determining the
      prognostic value of qSOFA in predicting mortality in patients with pneumonia.
      METHODS: Embase, Google Scholar, and PubMed (up to March 2018) were searched for
      related articles. We constructed a 2 * 2 contingency table according to mortality
      and qSOFA scores (<2 and >=2) in patients with pneumonia. Two investigators
      independently extracted data and assessed study eligibility. A bivariate meta
      analysis model was used to determine the prognostic value of qSOFA in predicting
      mortality. I index and Q-test were used to assess heterogeneity. RESULTS: Six
      studies with 17,868 patients were included. A qSOFA score >=2 was related to a
      higher risk for death in patients with pneumonia, with a pooled risk ratio (RR)
      was 3.35 (95% CI, 2.24-5.01) using a random-effects model (I = 89.4%). The pooled
      sensitivity and specificity of a qSOFA score >=2 to predict mortality in patients
      with pneumonia were 0.43 (95% CI, 0.33-0.53) and 0.86 (95% CI, 0.76-0.92),
      respectively. The diagnostic OR was 4 (95% CI, 3-6). The area under the summary
      receiver operator characteristic (SROC) curve was 0.67 (95% CI, 0.63-0.71). When
      we calculated the community-acquired pneumonia (CAP) subgroup, the pooled
      sensitivity and specificity were 0.36 (95% CI, 0.26-0.48) and 0.91 (95% CI, 0.84
      0.95), respectively. The area under the SROC curve was 0.70 (95% CI, 0.66-0.74).
      CONCLUSIONS: A qSOFA score >=2 is strongly associated with mortality in patients
      with pneumonia, but the poor sensitivity of qSOFA may have limitations in the
      early identification of mortality in patients with pneumonia.

PMID- 30290640
TI  - A meta-analysis of safety and efficacy of regorafenib for refractory metastatic
      colorectal cancer.
AB  - BACKGROUND: Patients with metastatic colorectal cancer (mCRC) often suffer from
      progressive disease despite previous therapy. It has been a great challenge for
      those patients. In 2012, regorafenib was approved for mCRC. In this meta
      analysis, we aimed to collect and present existing data to explorethe clinical
      use of regorafenib. METHODS: The online electronic databases, such as PubMed,
      Embase, and the Cochrane library, updated to November 2017 were systematically
      searched. Trials on the effectiveness of regorafenib in patients who suffer from
      treatment-refractory metastatic colorectal cancer were included, of which the
      main outcomes included 3 parameters: overall survival (OS), progression-free
      survival (PFS), and grade 3/4 AE. RESULTS: Totally, 4 trials were included in
      this meta-analysis. The OD was significantly better with the use of regorafenib
      (OR = 0.78, 95%CI = 0.65-0.94, I = 69%, P = .008), and PFS (OR = 0.52, 95%CI =
      0.34-0.79, I = 97%, P = .002). However, the most common toxicities occurred more
      frequently in the regorafenib group than the control group (OR = 3.73, 95%CI =
      1.68-8.28, I = 79%, P = .001). CONCLUSION: Regorafenib demonstrates better
      efficacy and has manageable adverse-event profile for treatment-refractory mCRC.
      Considering the safety feature of regorafenib, further studies and clinical
      trials are warranted to investigate the dosing of regorafenib and alternative
      approaches are needed to explore predictive biomarker fortherapy selection.

PMID- 30290641
TI  - Relationship between the anxiety/depression and care burden of the major
      caregiver of stroke patients.
AB  - To investigate the anxiety/depression of caregivers of stroke patients.This study
      used a cross-sectional survey design and convenience sampling.Totally, 117
      caregivers of stroke patients were enrolled. Data were collected from
      questionnaires. Hamilton anxiety scale, Hamilton depression scale, and Zarit
      caregiver burden interview were performed. Multiple linear regression and
      correlation analysis were used.The anxiety score, depression score and total
      burden score of 117 stroke caregivers were 16.56 +/- 8.02, 18.63 +/- 9.39, and
      25.88 +/- 10.35, respectively. Anxiety symptoms, mild to moderate depressive
      symptoms, and severe depressive symptoms were found in 43.9%, 26.5%, and 27.4% of
      the caregivers, respectively. Daily care time and medical payment method were
      influencing factors for anxiety and depression (P < .05). Both anxiety and
      depression were positively correlated with total care burden score (P <
      .01).Anxiety and depression are common in the caregivers of stroke patients and
      are closely related to care burdens. In this regard, appropriate home care
      guidance, psychological counseling and social support should be provided to the
      caregivers to reduce their physical and mental burden.

PMID- 30290642
TI  - A case report of Legionella and Mycoplasma pneumonia: Co-incidence or co
      infection?
AB  - RATIONALE: Concurrent or sequential coinfections of Legionella pneumophila and
      Mycoplasma pneumoniae have been reported in the past though infrequently.
      Distinguishing a true co-infection from cross reactivity is often challenging as
      the diagnosis is mostly dependent on serological testing. PATIENT CONCERNS: A 77
      year-old male presented with worsening dyspnea, cough with yellow sputum,
      diarrhea and fever of 2-days duration. Patient had history of chronic obstructive
      pulmonary disease (COPD) on home oxygen, bronchiectasis, rheumatoid arthritis (on
      methotrexate and leflunomide), treated pulmonary tuberculosis and 30-pack-year
      smoking. Chest X-ray showed bilateral interstitial changes with left lower lobe
      infiltrate. On day 5, his urine antigen for L pneumophila serogroup 1 was
      reported positive. The following day his serum M pneumoniae IgM antibody titers
      were reported elevated at 6647 U/mL. Patient was started on antibiotics and
      placed on non-invasive positive pressure ventilation. DIAGNOSIS: The patient was
      diagnosed with possible Legionella and Mycoplasma co-infection. OUTCOMES: Sputum
      Mycoplasma polymerase chain reaction (PCR) and serum cold agglutinins were
      obtained on day 6 and later reported negative. He was treated with azithromycin
      for 10 days with clinical improvement. LESSONS: Serological testing alone is an
      indirect measure with poor sensitivity and specificity and has its own
      limitations. Urine antigen detection confirms L pneumophila serogroup 1 infection
      in a patient with suggestive symptoms. However, diagnosis of M pneumonia should
      be based on combination of tests including serology and PCR to confirm true co
      infection.

PMID- 30290643
TI  - Induction therapy for clinical stage T2N0M0 esophageal cancer: A systematic
      review and meta-analysis.
AB  - OBJECTIVE: It is still controversial whether patients with clinical T2N0M0
      (cT2N0M0) esophageal cancer are treated with induction therapy. The aim of this
      study was to determine the effect of induction therapy on cT2N0M0 esophageal
      cancer. METHODS AND MATERIALS: We searched PubMed, Embase, the Cochrane Library,
      and Medline databases from inception up to May 1, 2017. This meta-analysis was
      performed to compare odds ratios (OR) for 5-year overall survival (OS),
      pathologically understaged and overstaged after esophagectomy. RESULTS: Eight
      retrospective studies of 2646 patients were included in the meta-analysis. Data
      showed that no statistically significant difference in 5-year over survival was
      observed between induction therapy group and direct operation group. The pooled
      OR and 95% confidence interval (CI) for 5-year OS were 0.92 (95% CI = 0.72-1.18;
      P = .52). Whereas, compared with induction therapy group, direct operation group
      had more pathologically understaged and less overstaged after esophagectomy.
      CONCLUSIONS: Currentclinical staging for T2N0M0 esophageal carcinoma remains
      inaccurate. In this study, we found that direct operation group had more
      pathologically understaged and less overstaged after esophagectomy compared with
      induction therapy group. Induction therapy could degrade the tumor staging but
      not improve the patient's survival.

PMID- 30290644
TI  - Quantitative evaluation of retinal artery occlusion using optical coherence
      tomography angiography: A case report.
AB  - RATIONALE: Retinal artery occlusion (RAO) results in painless, catastrophic
      vision loss in a period of seconds. Optical coherence tomography angiography
      (OCTA) can image retinal microcirculation, which is helpful to evaluate treatment
      response during the follow-up period. Using a single case with central RAO, we
      report its retinal perfusion changes before and after treatment using OCTA.
      PATIENT CONCERNS: A 36-year-old Chinese man came to our clinic with a sudden,
      painless loss of vision (hand motion) in his left eye. A vasodilator (nicotinic
      acid) was used as the primary treatment. OCTA imaging and a visual field
      examination were performed to assess the retinal perfusion changes before and
      after treatment. DIAGNOSIS: Retinal artery occlusion was considered.
      INTERVENTIONS: This patient was treated with an inhaled oxygen-carbon dioxide
      mixture, nicotinic acid tablets (100 mg) taken orally twice a day, and
      intravenous infusion of nicotinic acid injections (60 mg) combined with 0.9%
      sodium chloride injections (100 ml) once a day for vasodilation. OUTCOMES: After
      treatment and 9 months of follow-up, the vessel density of the left eye at the 9
      month follow-up appointment was improved in all quadrants. LESSONS: Retinal edema
      and retinal atrophy were observed at the RAO onset and several months later,
      respectively. However, macular perfusion gradually increased after treatment. The
      timely administration of a vasodilator and the presence of the cilioretinal
      artery play important roles in the prevention of profound vision loss.

PMID- 30290645
TI  - Th17 cells over 5.9% at admission indicate poor prognosis in patients with HBV
      related acute-on-chronic liver failure.
AB  - Our previous study demonstrated that Th17 cells increased significantly in
      patients with hepatitis B virus-related acute-on-chronic liver failure (HBV
      ACLF). However, their prognostic role in HBV-ACLF patients remains unknown.Sixty
      eight consecutive HBV-ACLF patients were enrolled in this cohort study. Th17
      cells were examined using flow cytometry. Disease severity scores were assessed.
      ROC curves were used to evaluate the value in predicting prognosis. Survival was
      analyzed using Kaplan-Meier curves. Predictors of mortality were determined by
      regression analysis.Th17 cells were significantly higher in HBV-ACLF patients
      compared to patients with chronic hepatitis B and normal controls (both P <
      .001). Also, Th17 cells were higher in nonsurviving HBV-ACLF patients than in
      surviving patients (P = .014). Th17 cells were positively correlated with CLIF
      Consortium ACLF (CLIF-C ACLF) score (r = 0.240, P = .048). ROC curves showed that
      the frequency of Th17 cells had accuracy in predicting 90-day prognosis
      equivalent to MELD, MELD-Na and CLIF-C ACLF scores in HBV-ACLF (P = .34, P = .26,
      and P = .15, respectively). More importantly, the area under the ROC curve
      (AUROC) increased when Th17 cells were combined with MELD, MELD-Na or CLIF-C ACLF
      score than using Th17 cells alone (P = .021, P = .006, and P = .023,
      respectively). Kaplan-Meier analysis revealed that higher Th17 cells (>=5.9%)
      were closely associated with poor overall survival in HBV-ACLF (P = .0086).
      Additionally, multivariate regression analysis showed that the frequency of Th17
      cells over 5.9% was an independent predictor of mortality (OR = 0.154, P =
      .025).Circulating Th17 cells positively correlated with disease severity in HBV
      ACLF. The frequency of Th17 cells over 5.9% could serve as a prognostic biomarker
      for HBV-ACLF patients.

PMID- 30290646
TI  - Effect of Liuzijue Qigong on patients with chronic obstructive pulmonary disease:
      Protocol for a systematic review and meta-analysis.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of
      morbidity and mortality worldwide with a substantial and increasing social and
      economic burden. Liuzijue Qigong is a kind of traditional Chinese Qigong
      exercises that Traditional Chinese Medicine practitioners prescribe to
      individuals with COPD to strengthen the internal organs' function. Liuzijue
      Qigong was recommended for use in COPD rehabilitation, and some clinical trials
      indicate that Liuzijue Qigong would produce better functional capacity and
      quality of life of individuals with COPD. The objective of this study is to
      conduct a systematic review of the existing studies to assess effectiveness and
      safety of Liuzijue Qigong for the prevention or treatment of COPD in patients.
      METHODS: We will perform the comprehensive literature search in English and
      Chinese electronic database. The publication period will be from inception to the
      search date. In addition, the clinical trial registries, dissertations, informal
      publication, grey literature, reference lists of studies, systematic reviews, and
      conference abstracts will also be collected. Two reviewers will identify relevant
      studies, extract data information, and then assess the methodical quality by the
      Cochrane risk of bias assessment tool. Only randomized controlled trials
      comparing Liuzijue Qigong against other intervention or nonintervention will be
      included. Data will be synthesized by either fixed-effect or random-effect model
      regarding to a heterogeneity test. The routine lung function, arterial blood gas
      tensions, partial pressure of carbon dioxide, functional capacity, 30 seconds sit
      to-stand test, respiratory function, maximal inspiration pressure, maximal
      expiratory pressure, airway resistance, and specific airway conductance will be
      assessed as primary outcomes. The secondary outcomes involved dyspnea, and
      fatigue levels, respiratory muscle strength, upper and lower limb muscle
      strength, handgrip strength test, and health-related quality of life and safety.
      Meta-analysis will be performed by using Cochrane's Review Manager software
      (version 5.3.5). RESULTS: This systematic review and meta-analysis will provide a
      high-quality synthesis and evaluate the efficacy and safety based on current
      relevant literature evidence of Liuzijue Qigong intervention for COPD patient.
      CONCLUSION: Our systematic review will provide evidence to determine whether
      Liuzijue Qigong is an effective and safe approach to prevention and treatment of
      COPD patients.

PMID- 30290647
TI  - An observational study of the epidermal growth factor receptor-tyrosine kinase
      inhibitor resistance mechanism in epidermal growth factor receptor gene mutation
      positive non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor
      (EGFR) mutation show a high response to EGFR-tyrosine kinase inhibitor (EGFR
      TKI). Clinically, EGFR-positive NSCLC acquires several resistance mechanisms
      during EGFR-TKI treatment, such as the emergence of a secondary mutation (T790M),
      MET gene amplification, and transformation to small cell lung cancer. However,
      the mechanism of resistance to afatinib, a second-generation EGFR-TKI, remains
      unclear. In this study, we prospectively investigate the mechanism of resistance
      to afatinib using proteomic analyses.In total, 35 EGFR-positive NSCLC patients of
      both sexes and >=20 years old will be included. NSCLC patients with major
      obstacles in major organs, such as bone marrow, heart, lung, liver, and kidney,
      will be excluded. Eligible patients will be administered afatinib or gefitinib
      until disease progression and proteomic analysis will be performed with biopsy
      samples before treatment and at disease progression.The primary outcome is to
      detect the potential predictive anomalies in proteins that can be candidates for
      the resistance factor of afatinib. The secondary outcome is to detect gene and
      protein abnormalities affecting progression-free survival, response rate, and
      rate of disease control in afatinib therapy.The protocol was approved by the
      institutional review boards of Kyoto Prefectural University of Medicine and all
      the participating hospitals. Written informed consent was obtained from all
      patients before registration, in accordance with the Declaration of Helsinki. The
      results of the study will be disseminated via publications in peer-reviewed
      journals.Trial registration number is UMIN000031013.

PMID- 30290648
TI  - Fecal microbiota transplantation for patients with irritable bowel syndrome: A
      meta-analysis protocol.
AB  - Irritable bowel syndrome (IBS) is a common functional bowel disease characterized
      by chronic or recurrent abdominal pain, bloating, constipation, and diarrhea.
      Many patients with IBS have a poor quality of life due to abdominal discomfort,
      diarrhea, constipation, and the presence of other diseases. At present,
      intestinal motility inhibitors, adsorbents, astringents, intestinal mucosal
      protective agents, and antidepressants have been combined to treat IBS, but the
      treatment process is long, which results in a large economic burden to patients.
      Fecal microbiota transplantation (FMT) is a treatment involving the
      transplantation of functional bacteria from healthy human feces into the
      gastrointestinal tract of patients; thus, replacing the intestinal flora and
      modulating intestinal and extra-intestinal diseases. In recent years, the
      efficacy and economic benefits of FMT in the treatment of IBS have received
      increasing attention from researchers.A search for randomized controlled trials
      (RCTs) on treating IBS with FMT will be performed using 9 databases, including
      PubMed, the Cochrane Library, Embase, ClinicalTrails, China National Knowledge
      Infrastructure, Sino Med, ScienceDirect, VIP, and Wanfang Data. Two reviewers
      will independently screen data extraction studies and assess study quality and
      risk of bias. The risk of bias for each RCT will be assessed against the Cochrane
      Handbook standards to assess methodological quality. RevMan V.5.3 software will
      be used to calculate data synthesis when meta-analysis is allowed.This study will
      provide a high-quality synthesis of existing evidence on the effectiveness and
      safety of FMT in the treatment of IBS.This study will determine if FMT is an
      effective and safe intervention for IBS.PROSPERO registration number is PROSPERO
      CRD42018108080.

PMID- 30290649
TI  - Predictive factors of postoperative complications in single-port video-assisted
      thoracoscopic anatomical resection: Two center experience.
AB  - The purpose of this study was to identify the risk factors for adverse events
      during single-port video-assisted thoracoscopic (SPVATS) anatomical resections.We
      retrospectively reviewed patients who had undergone SPVATS anatomic resections
      between January 2014 and February 2017 in Coruna University Hospital's Minimally
      Invasive Thoracic Surgery Unit (CHUAC, Spain) and Chang Gung Memorial Hospital
      (CGMH, Taiwan). Four hundred forty-two patients (male: 306, female: 136) were
      enrolled in this study. Logistic regression analysis was performed on variables
      for postoperative complications.Postoperative complications with a 30-day
      mortality occurred in 94 patients (21.3%) and with a 90-day mortality in 3
      patients (0.7%) while the major complication rate was 3.9%. Prolonged air leak
      (PAL > 5 days) was the most common complication and came by postoperative
      arrhythmia. Logistic regression indicated that pleural symphysis (odds ratio
      (OR), 1.91; 95% confidence interval (CI), 1.14-3.18; P = .014), computed
      tomography (CT) pulmonary emphysema (OR, 2.63; 95% CI, 1.41-4.76; P = .002), well
      developed pulmonary CT fissure line (OR, 0.49; 95% CI, 0.29-0.84; P = .009), and
      tumor size (>=3 cm) (OR, 2.15; 95% CI, 1.30-3.57; P = .003) were predictors of
      postoperative complications.Our preliminary results revealed that SPVATS anatomic
      resection achieves acceptable 30- and 90-day surgery related mortality (0.7%) and
      major complications rate (3.9%). Prolonged Air leak (PAL > 5 days) was the most
      common postoperative complication. Pleural symphysis, pulmonary emphysema, well
      developed pulmonary CT fissure line and tumor size (>=3 cm) were predictors of
      adverse events during SPVATS anatomic resection.

PMID- 30290650
TI  - New vertebral fractures after osteoporotic vertebral compression fracture between
      balloon kyphoplasty and nonsurgical treatment PRISMA.
AB  - BACKGROUND: Because of aging of population, osteoporotic vertebral compression
      fracture (OVCF) appears an increasing incidence rate. Conservative therapy (CT)
      and balloon kyphoplasty (BKP) have been used to treat OVCFs. However, an increase
      in new vertebral compression fractures at nontreated levels following BKP is of
      concern. It is still not clear whether new fractures were a result of BKP and the
      purpose of this meta-analysis was to evaluate the new fractures risk after BKP
      compared with CT. METHODS: An exhaustive literature search of PubMed, EMBASE, and
      the Cochrane Library was conducted to identify randomized controlled trials and
      prospective nonrandomized controlled study that compared BKP with CT for patients
      suffering OVCF. A random-effect model was used. Results were reported as
      standardized mean difference or risk ratio with 95% confidence interval. RESULTS:
      Twelve studies were included and there was no significant difference in total new
      fractures (P = .33) and adjacent fractures (P = .83) between 2 treatments.
      Subgroup analyses did not demonstrate significant differences in follow-up
      period, mean age, anti-osteoporosis therapy, and the proportion of women.
      CONCLUSION: Our systematic review revealed that an increased risk of fracture of
      vertebral bodies was not associated with BKP compared with CT.

PMID- 30290651
TI  - Inflammatory myofibroblastic lung tumor transforming into intracranial
      desmoplastic noninfantile ganglioglioma: A case report and literature review.
AB  - RATIONALE: Inflammatory myofibroblastic tumor (IMT) of the lung often arises from
      excessive inflammatory response. It is one of the rare benign tumors of the lung,
      while desmoplastic noninfant gangliogliomas (DNIG), on the contrary, are rare
      intracranial benign tumors often seen in children within the first one and a half
      years of life. PATIENT CONCERNS: We present a 12-year-old girl with 2 months
      history of none productive cough and right-sided chest pain. DIAGNOSES: Computer
      tomography scan of the chest revealed a soft tissue mass at the right upper lobe
      which was consistent with IMT. Histopathologic examination confirmed the
      diagnosis of IMT. INTERVENTIONS: Thoracic surgery was successfully carried out
      and she further received radiotherapy. The patient recovered initially. OUTCOMES:
      Two years later, she complained of seizures during follow-up. Magnetic resonance
      imaging of the head revealed DNIG. We achieved total resection of the major
      lesions and she was further treated with radiotherapy. She is currently well and
      in school. Histopathologic examination confirmed the diagnosis of DNIG. LESIONS:
      We speculate that IMT might have transformed into intracranial DNIG through
      metastatic process or as a result of genetic mutations or chromosomal abrasions.

PMID- 30290652
TI  - Early stage ovarian carcinoma with symptoms mimicking tuberculous peritonitis in
      a postmenopausal woman: A case report.
AB  - RATIONALE: Ovarian cancer has the poorest prognosis of the gynecological cancers.
      Early diagnosis and treatment are important, but early-stage ovarian carcinoma
      has nonspecific symptoms. Ultrasonography, computed tomography, magnetic
      resonance imaging, and serum CA-125 levels can be helpful but may not elucidate
      cases of diffuse peritoneal diseases mimicking carcinomatosis. PATIENT CONCERNS:
      The patient had intermittent abdominal discomfort and dysuria. Abdominal-pelvic
      computed tomography findings were suspicious for peritoneal tuberculosis (TB) and
      a small cystic mass in the left ovary. The CA-125 values were normal. DIAGNOSES:
      She underwent laparoscopy for pathologic confirmation of tuberculous peritonitis
      and management of the ovary mass. Bilateral adnexectomy was performed.
      Histopathological examination of the surgical specimen revealed a serous ovarian
      carcinoma in her left ovary and salpinx. INTERVENTIONS: Laparoscopic
      hysterectomy, pelvic lymphadenectomy, para-aortic nodal dissection, and
      omentectomy were carried out for staging evaluation. OUTCOMES: We encountered a
      rare case of ovary cancer stage IA serous ovarian carcinoma incidentally
      discovered by laparoscopy in a postmenopausal woman. She received adjuvant
      chemotherapy without relapse. LESSONS: Peritoneal TB may mimic peritoneal or
      ovarian carcinoma, but the reverse case is rare. Hence, gynecologists should be
      careful in assessment of patients before treatment.

PMID- 30290653
TI  - Prepregnancy obesity status and risks on pregnancy outcomes in Shanghai: A
      prospective cohort study.
AB  - Obesity in women of reproductive age is not only associated with numerous adverse
      maternal and fetal effects prenatally but also exerts a negative influence on
      female fertility. The aim of this study was to investigate the situation of
      prepregnant obesity in Shanghai and explore the impact of prepregnant obesity on
      gestational weight gain as well as other pregnancy outcomes. A prospective
      hospital-based pregnant women cohort was established in Shanghai since January
      2015. All pregnant women who were registered and expected to deliver in this
      hospital were included in the cohort. Nearly one fourth of pregnant women in
      Shanghai were overweight/obese and the prevalence of overweight/obesity was more
      common among women with advancing age (P < .001). Women prepregnancy
      overweight/obesity was associated with 3.5-fold higher risk of excessive
      gestational weight gain (odds ratio, OR 3.58; 95% confidence interval, CI, 2.82
      4.55; P < .001). Women prepregnancy BMI was statistically related to pregnancy
      outcomes as macrosomia (OR 2.24; 95% CI, 1.55-3.23; P < .001), cesarean delivery
      (OR 2.04; 95% CI, 1.60-2.62; P < .001), maternal complications (OR 1.53; 95% CI,
      1.18-1.98; P < .001). Prepregnancy obesity is associated with a much higher risk
      of excessive gestational weight gain and pregnancy outcomes in Shanghai. Further
      interventions targeting maternal obesity, especially prepregnancy obesity are
      required.

PMID- 30290654
TI  - Bystander cardiopulmonary resuscitation training in primary and secondary school
      children in China and the impact of neighborhood socioeconomic status: A
      prospective controlled trial.
AB  - BACKGROUND: The World Health Organization (WHO) has endorsed school bystander
      cardiopulmonary resuscitation (CPR) training programs. But related researches in
      China are limited. Therefore, we conducted this study to assess bystander CPR
      training in school children in China and the impact of neighborhood socio
      economic status (SES) on. METHODS: A total of 1,093 students from seven schools
      in Zhejiang province participated in this study. Theoretical and practical
      bystander CPR training were conducted in instructor-led classes. Students
      completed a 10-statement questionnaire before and after training, and then
      underwent a skills assessment during a simulated basic life support (BLS)
      scenario. Subgroup analyses were stratified according to neighborhood SES.
      RESULTS: Before training, most students (72.83%) had a strong desire to learn
      bystander CPR and share with others. After training, bystander CPR theory was
      significantly improved (P < .01), and 92.64% students reached an 85-100%
      performance rate in a simulated BLS scenario. Students from low-SES neighborhoods
      had less pre-training knowledge of bystander CPR (P < .01). However, their
      performance was similar with students from higher-SES neighborhoods on the post
      training questionnaire and the skills assessment, and better among students aged
      13-14 years. CONCLUSION: School children in China have a poor pre-training
      knowledge of bystander CPR. However, with training, there was a significant
      improvement in the basic theory and skills of CPR. Bystander CPR training efforts
      should be targeted to Chinese primary and secondary school children, especially
      in low-SES neighborhoods.

PMID- 30290655
TI  - Admissions to intensive cardiac care units in France in 2014: A cross-sectional,
      nationwide population-based study.
AB  - Geographic variation in admission to the intensive cardiac care unit (ICCU) might
      question about the efficiency and the equity of the healthcare system. The aim
      was to explain geographic variation in the rate of admission to ICCU for coronary
      artery disease (CAD) or heart failure (HF) in France.We conducted a retrospective
      study based on the French national hospital discharge database. All inpatient
      stays for CAD or HF with an admission to an ICCU in 2014 were included. We
      estimated population-based age and sex-standardized ICCU admission rates at the
      department level. We separately modeled the department-level admission rates for
      HF and CAD using generalized linear models.In all, 61,010 stays for CAD and
      27,828 stays for HF had at least 1 ICCU admission. The ICCU admission rates were
      explained by the admission rate for CAD, by the diabetes prevalence, by the
      proportion of the population >75 years, and by the drive time to the ICCU.This
      work sheds light on the finding of substantial geographic variation in the ICCU
      admission rates for CAD and HF in France. This variation is explained by both the
      age and the health status of the population and also by the drive time to the
      closest ICCU for HF. Moreover, ICCU admission for HF might be more prone to
      unwarranted variations due to medical practice patterns.

PMID- 30290656
TI  - Comparing stand-alone oblique lumbar interbody fusion with posterior lumbar
      interbody fusion for revision of rostral adjacent segment disease: A STROBE
      compliant study.
AB  - Spinal fusion has become a standard treatment for symptomatic intervertebral
      degenerative disc disease. The present study aimed to compare perioperative
      parameters, clinical outcomes, and radiographic results of stand-alone oblique
      lumbar interbody fusion (OLIF) with posterior lumbar interbody fusion (PLIF) for
      the revision of rostral adjacent segment disease (ASD) following prior posterior
      lumbar fusion.Thirty-six patients who underwent revision surgeries for rostral
      ASD were retrospectively reviewed. Among them, 17 patients underwent stand-alone
      OLIF (OLIF group) and 19 patients underwent PLIF (PLIF group). The length of
      operation, intraoperative hemorrhage, bed rest duration, and length of hospital
      stay were compared between the 2 groups. Clinical results were evaluated with the
      Oswestry Disability Index (ODI) and visual analog scale (VAS). Radiological
      results were evaluated with disc height (DH), foraminal height (FH),
      retrolisthesis index (RI), and lumbar lordosis (LL), as well as the fusion rate
      and cage subsidence. Follow-up results at 1 week, 3 months, and 12 months
      postoperatively were compared between the 2 groups.The OLIF group had less
      intraoperative blood loss, shorter operative time, bed rest time, and hospital
      stay than did the PLIF group (P < .05). The OLIF group had lower VAS scores for
      back pain than the PLIF group at 1 week and 3 months postoperatively (P < .05),
      and lower VAS scores for leg pain than the PLIF group at 1 week postoperatively
      (P < .05). The OLIF group had lower ODI than the PLIF group at 1 week and 3
      months postoperatively (P < .05). No significant differences were found in DH and
      FH between the 2 groups preoperatively (P > .05); the OLIF group showed higher DH
      and FH than the PLIF group at all time points (P < .05). No significant
      differences were found in RI and LL between the 2 groups at any time point. All
      patients achieved fusion at 12 months postoperatively, and cage subsidence was
      not observed in either group.OLIF is effective and safe for the treatment of
      rostral ASD following prior posterior lumbar fusion, and is superior to PLIF in
      terms of perioperative parameters, short-term clinical outcomes, and DH
      restoration, with similar fusion and reduction rates.

PMID- 30290657
TI  - Factors influencing class agreement and medical expenditure by age in South
      Korea.
AB  - BACKGROUND: There are not many studies evaluating the factors affecting medical
      expenditure for different age groups, income classes, and subjective social
      classes. Therefore, this study evaluates the agreement between income class,
      objective class, and subjective social class and analyzes the factors that affect
      medical expenditure by age group. METHODS: Multiple regression analysis and chi
      test were conducted to evaluate the compatibility between income quintiles and
      subjective social classes and to identify the factors influencing medical
      expenditure by subjective social class and age using raw data from the 2013 Korea
      Health Panel (n = 9,385) of the Korea Institute for Health and Social Affairs and
      the National Health Insurance Service. RESULTS: When the class compatibility
      between income quintiles and subjective social classes was analyzed by age group,
      young people in the first, second, and third income quintiles considered
      themselves to be in the second subjective social class while and those in the
      fourth and fifth income quintiles considered themselves to be in the third
      subjective social class. Moreover, middle-aged and old people in the first,
      second, third, and fourth income quintile considered themselves to be in the
      second subjective social class while those in the fifth income quintile
      considered themselves to be in the third subjective social class. CONCLUSION:
      Social support, public health approaches, and medical treatment service models
      are needed to eliminate comparative deprivation among individuals.

PMID- 30290658
TI  - Young male breast cancer, a small crowd, the survival, and prognosis?: A
      population-based study.
AB  - Women diagnosed with breast cancer at young age often have poorprognoses. Yet,
      few studies have focused on the prognoses of young men with breast cancer. We
      therefore used Surveillance, Epidemiology, and End Results (SEER) population
      based data and identified 151 male patients with breast cancer aged <40 years
      between 1988 and 2012. Propensity score matching analysis was used to balance the
      clinical variables among different groups. Kaplan-Meier curves were applied to
      compare the survival differences. The subgroup variables on cancer-specific
      survival (CSS) and overall survival (OS) were analyzed by the Cox proportional
      hazard model. Results showed that male patients with breast cancer aged <40 had a
      significant OS benefit compared with those aged >=40 years (P < .001). The
      significant difference of the CSS was not found (P > .05). Compared with the male
      patients with breast cancer aged >=40, those aged <40 had significant OS benefit
      in most subgroups (P < .05). Compared with the female patients with breast cancer
      aged <40, the male patients with breast cancer aged <40 had worse OS and CSS
      benefit only in the subgroup with progesterone receptor and estrogen receptor
      positive (P < .05). In conclusion, we demonstrated that young male patients with
      breast cancer had better OS compared with elder male patients with breast cancer.
      However, the survival benefit was not found compared with young female patients
      with breast cancer.

PMID- 30290659
TI  - Significance of contrast-enhanced ultrasonography in differential diagnosis of
      thyroid nodules.
AB  - The present study was aimed to compare the application values between 2
      dimensional color Doppler ultrasonography (2DUS) and contrast-enhanced
      ultrasonography (CEUS) in the differential diagnosis of thyroid malignant
      nodules.A total of 124 patients suspectedly diagnosed with malignant thyroid
      nodules under conventional gray-scale ultrasonography were recruited in this
      study. All enrolled patients were examined by both 2DUS and CEUS.A total of 153
      nodules (94.44%) and 45 cases (90.00%) with malignant nodules were detected by
      the CEUS. No significant differences were noted in nodule detection rates between
      2DUS and CEUS (chi = 1.170, P = .279; chi = 0.796, P = .372). The aspect ratio,
      microcalcification, internal echo, borderline, Vmax, resistance index, and total
      scores of malignant nodules were higher than those of benign nodules (all P <
      .05) when diagnosed by 2DUS. The peripheral/internal enhancement time, peak
      intensity, local enhancement, ring enhancement, and total scores of malignant
      nodules were significantly higher compared with those of benign nodules (all P <
      .05) by CEUS. Total score of malignant nodules diagnosed by 2DUS was
      approximately 3.5 and 2.3 points for CEUS. The diagnostic accuracy of 2DUS as
      observed by area under the curve was 0.821 with the cut-off value of 3.9, the
      sensitivity was 82.5%, and the specificity was 85.6%. The diagnostic accuracy of
      CEUS was 0.862 with the cut-off value of 2.8, the sensitivity was 86.7%, and the
      specificity was 91.3%.Both 2DUS and CEUS are worthy of application values in the
      differential diagnosis from benign to malignant thyroid nodules.

PMID- 30290660
TI  - Comparison of diabetes risk estimate in the cities of Riyadh and Amman.
AB  - A significant rise in the prevalence of type 2 diabetes mellitus (T2DM) in the
      Middle-east and North Africa (MENA) region has seen over the last few decades.
      The present observational study aimed to evaluate and compare the risk of
      developing T2DM in the cities of Riyadh and Amman using the Arab Diabetes Risk
      Assessment Questionnaire (ARABRISK).The ARABRISK was administered in a total of
      1116 healthy male and female individuals in the age group of 40 to 74 years with
      no prior history of diabetes in the city of Riyadh (Saudi Arabia) and Amman
      (Jordan). ARABRISK is an Arabic version of the Canadian Diabetes Risk Assessment
      Questionnaire (CANRISK), which was adapted and validated for the use in Arab
      speaking individuals in Saudi Arabia and Jordan.The participants from Amman
      region had higher mean total ARABRISK score compared to the Riyadh region for all
      categories of ARABRISK. However, the difference was significant in both low- and
      high-risk categories (P = .02 and P = .01, respectively) but not significant for
      moderate category (P = .17). In the Riyadh population, female participants had
      significantly higher ARABRISK total scores compared to male in both moderate- and
      high-risk categories (P = .01). However, in the Amman population, male
      participants had significantly higher ARABRISK total scores compared to female in
      both low- and moderate-risk categories (P = .01).The present study suggested an
      increased risk of developing T2DM in the cities of Riyadh and Amman. However, the
      population of Amman had a higher risk of developing T2DM compared to the
      population of Riyadh.

PMID- 30290661
TI  - Retrospective analysis of concurrent docetaxel and epirubicin neoadjuvant versus
      adjuvant chemotherapy: Which leads to better outcomes for different subtype
      breast cancer patients?
AB  - Different biological subtype breast cancers respond differently to neoadjuvant
      chemotherapy, but it is unknown whether neoadjuvant or adjuvant chemotherapy
      leads to different long-term survival in each specific subtype although equal
      outcomes have been reported in general population. This study sought to clarify
      whether the selection of either neoadjuvant or adjuvant chemotherapy was linked
      to a differential survival benefit based on breast cancer subtypes.A
      prospectively maintained breast cancer database was queried from 2000 to 2008.
      All patients with a diagnosis of stage II and III breast cancer who received
      neoadjuvant or adjuvant chemotherapy were identified, only patients receiving
      docetaxel and epirubicin (TA) regimen were included. Patients were divided
      according to the administration of neoadjuvant or adjuvant chemotherapy. The
      biological subtypes were determined by immunohistochemical tests. The outcomes
      between neoadjuvant and adjuvant chemotherapy were compared in each different
      subtype. Kaplan-Meier curves were generated, and the Cox model was used to
      estimate the association between death risk and chemotherapy timing while
      adjusting for potentially confounding factors. P values < .05 were considered
      statistically significant.Of the 406 patients included, 201 (49.5%) received
      neoadjuvant chemotherapy, and 205 (50.5%) received an adjuvant TA regimen.
      Patients with the HER2+ and TNBC subtypes showed significantly higher pCR rates
      than patients with luminal types (P < .05). In general population, the
      neoadjuvant and adjuvant chemotherapy groups showed little survival variance
      (HR=1.15, 95% confidence interval (CI) .69-1.91, P=.60). In luminal B-like
      patients, neoadjuvant chemotherapy led to worse overall survival (OS) than
      adjuvant therapy (HR=2.92, 95%CI 1.20 to 8.31, P = .02). In patients with the
      HER2+ subtype, neoadjuvant treatment corresponded to better OS (HR = .10, 95%CI
      .02-.58, P = .01). In contrast, patients with luminal A-like (HR = 1.14, 95%CI
      .53-2.43, P = .74) and TNBC disease (HR = 1.00, 95%CI .27-3.73, P = >.99) who
      underwent neoadjuvant chemotherapy showed equivalent OS when compared to patients
      undergoing adjuvant therapy.Neoadjuvant versus adjuvant chemotherapy results in a
      disparate impact on overall survival among patients with variant subtype breast
      cancer. When neoadjuvant chemotherapy was given, luminal B-like patients showed
      worse outcome, while patients with HER2+ disease had better OS. Prospective
      studies are necessary to determine and optimize the timing of chemotherapy for
      breast cancers with different molecular backgrounds.

PMID- 30290662
TI  - Indocyanine green angiography for preserving the ureteral branch of the uterine
      artery during radical hysterectomy: Two case report.
AB  - RATIONALE: Conventional radical hysterectomy is frequently associated with
      postoperative ureteral ischemic necrosis, urinary fistula, stenosis, and kidney
      seeper. Some have suggested that preserving the ureteral branch during radical
      hysterectomy may reduce the incidence of ureteral complications. However, the
      feasibility of such preservation has not been explored using intraoperative
      imaging techniques. PATIENT CONCERNS: Two cervical cancer patients aged 45 and 53
      years were selected to undergo surgery in our hospital in October 2017. Both
      patients showed normal function of major organs and no special treatment was
      deemed necessary based on their subjective symptoms and preoperative examination.
      DIAGNOSES: Both patients were diagnosed with cervical cancer in stage Ib1
      according to the staging scheme of the International Federation of Gynecology and
      Obstetrics (FIGO 2009). INTERVENTIONS: Two patients underwent ureteral branch
      sparing radical hysterectomy. During surgery, indocyanine green (ICG)
      fluorescence angiography was used to identify the ureteral branch and evaluate
      perfusion of the uterine artery, its ureteral branch and the ureter. OUTCOMES:
      The uterine artery and ureteral branch were clearly labeled by green
      fluorescence, as were the distal serous layer of the ureter and tissue supplied
      by the ureteral branch. During 4-month follow-up, neither patient suffered
      hydronephrosis, ureteral fistula or stricture. LESSONS: ICG angiography is a
      useful intraoperative imaging technique for identifying the ureteral branch and
      evaluating the branch-sparing surgery. Based on real-time angiography, sparing
      the ureteral branch can maintain blood supply to the ureter distal serous layer
      and neighboring tissues.

PMID- 30290663
TI  - The efficacy of accommodative versus monofocal intraocular lenses for cataract
      patients: A systematic review and meta-analysis.
AB  - INTRODUCTION: We performed a systematic review and meta-analysis to evaluate
      whether accommodative intraocular lenses (AC-IOLs) are superior for cataract
      patients compared with monofocal IOLs (MF-IOLs). METHODS: Pubmed, Embase,
      Cochrane library, CNKI, and Wanfang databases were searched through in August
      2018 for AC-IOLs versus MF-IOLs in cataract patients. Studies were pooled under
      either fixed-effects model or random-effects model to calculate the relative risk
      (RR), weighted mean difference (WMD), or standard mean difference (SMD) and their
      corresponding 95% confidence interval (CI). Distance-corrected near visual acuity
      (DCNVA) was chosen as the primary outcome. The secondary outcomes were corrected
      distant visual acuity (CDVA), pilocarpine-induced IOL shift, contrast
      sensitivity, and spectacle independence. RESULTS: Seventeen studies, involving a
      total of 1764 eyes, were included. Our results revealed that AC-IOLs improved
      DCNVA (SMD = -1.84, 95% CI = -2.56 to -1.11) and were associated with
      significantly greater anterior lens shift than MF-IOLs (WMD = -0.30, 95% CI = 
      0.37 to -0.23). Furthermore, spectacle independence was significantly better with
      AC-IOLs than with MF-IOLs (RR = 3.07, 95% CI = 1.06-8.89). However, there was no
      significant difference in CDVA and contrast sensitivity between the 2 groups.
      CONCLUSION: Our study confirmed that AC-IOLs can provide cataract patients with
      DCNVA and result in more high levels of spectacle independence than MF-IOLs.
      Further studies with larger data set and well-designed models are required to
      validate our findings.

PMID- 30290664
TI  - The risk factors for bone metastases in patients with colorectal cancer.
AB  - This retrospective analysis aim to evaluate the potential risk factors for bone
      metastases (BM) in patients who were diagnosed with colorectal cancer (CRC).A
      total of 2790 patients diagnosed with CRC between January 2006 and December 2016
      were collected in this study. All patients were divided into 2 groups, BM and no
      BM. The associations between biomarkers (including age, gender, histopathological
      types, alkaline phosphatase (ALP), carcinoembryonic antigen (CEA), cancer antigen
      125, and so on), and BM in patients with CRC were analyzed. All the analyses were
      conducted by SPSS software (version 22.0, SPSS, Chicago, IL).Of all patients, 74
      (2.7%) were identified with BM. The level of serum ALP, CEA, and cancer antigen
      125 in patients with BM were obviously higher than those without BM (P < .001, P
      = .005, and P < .001). And the cut-off values of ALP, CEA, and cancer antigen 125
      were 85.5 U/L, 6.9 mmol/L, and 16.8 mmol/L, respectively.ALP, CEA, and cancer
      antigen 125 were identified as the independent risk factors for BM in patients
      with CRC.

PMID- 30290665
TI  - Targeted high-throughput sequencing technique for the molecular diagnosis of
      primary immunodeficiency disorders.
AB  - The aim of this study was to investigate the usefulness of targeted high
      throughput sequencing (HTS) for the molecular diagnosis of primary
      immunodeficiency diseases (PID).A total of 56 clinically diagnosed or suspected
      PID patients were divided into 4 groups according to the International Union of
      Immunological Societies Expert Committee for Primary Immunodeficiency 2015 and
      their chief clinical presentations. Patients and their biological family members
      were examined by targeted HTS, which sequenced the exons and +/-10 bp flanking
      introns of 171 PID-related genes panel. All significant variants were confirmed
      by PCR-Sanger sequencing. Pathogenicity of the variants was evaluated by using
      bioinformatics.A total of 117 variants in 73 genes were found in 56 patients.
      Accurate molecular diagnosis of PID was made in 13 (23.2%) patients, and 12 novel
      mutations were detected in these patients. Twenty-seven patients carried
      heterozygous variants that are probably pathogenic in >=2 genes; 16 patients had
      only 1 missense variant, or had several variants but not >1 variant was
      deleterious as evaluated by bioinformatics. The meaning of the targeted HTS
      results of these patients remains to be studied.Targeted HTS can make a precise
      molecular diagnosis of PID and detect more novel pathogenic mutations. More and
      more variations with ambiguous significance are discovered and explanation of
      these variations is a challenge to the clinicians.

PMID- 30290666
TI  - A novel fibrinogen variant in a Chinese pedigree with congenital
      dysfibrinogenemia caused by FGA P. Arg38Thr mutation: A case report.
AB  - RATIONALE: Congenital dysfibrinogenemia (CD) is characterized by altered
      functional properties of the fibrinogen; people who suffer from CD often have a
      low activity of fibrinogen and the mutation in the genomic DNA. PATIENT CONCERNS:
      A 6-year-old child was examined with a low activity of fibrinogen measured by Von
      Clauss method and PT-derived method which indicated a normal level of fibrinogen;
      this abnormality was also detected in her mother. The genomic DNA of all the
      family members was extracted, and all exons of 3 fibrinogen genes which encode
      fibrinogen alpha chain (FGA), fibrinogen beta chain (FGB), and fibrinogen gamma
      chain (FGG) were amplified by polymerase chain reaction (PCR), in addition,
      sanger sequencing, homologous sequence alignment and bioinformatics software were
      performed for the further analysis. DIAGNOSES: CD in this pedigree is associated
      with c.113G>C in the exon 2 of FGA which caused Arg38Thr mutation. OUTCOMES: The
      child and her mother showed a low plasma concentration of fibrinogen measured by
      Von Clauss method, whereas a normal result measured by PT-derived method;
      finally, c.113G>C in the exon 2 of FGA was detected in the pedigree which caused
      Arg38Thr mutation and it is the first report on a pedigree with CD caused by
      AalphaArg38Thr. LESSONS: This case gives us the lesson that not all patients with
      CD showed typical symptoms and laboratory test results; the result of fibrinogen
      concentration and antigen which is tested by Von Clauss method and
      immunoturbidimetric assay is various according to the condition of each CD
      patient.

PMID- 30290667
TI  - Patient quality of recovery on the day of surgery after propofol total
      intravenous anesthesia for vitrectomy: A randomized controlled trial.
AB  - BACKGROUND: Vitrectomy under general anesthesia is considered as a candidate for
      ambulatory surgery. An anesthetic method with high quality of postoperative
      recovery should be selected for successful ambulatory surgery. We thus compared
      quality of postoperative recovery on the day of vitrectomy using the Quality of
      Recovery (QoR)-40 questionnaire between propofol total intravenous anesthesia
      (propofol group) and desflurane inhalation anesthesia (desflurane group) as the 2
      representative anesthetic methods. METHODS: Eighty-four patients (20-80 years
      old) undergoing elective vitrectomy under general anesthesia were randomized into
      2 groups. The propofol group received propofol and remifentanil using effect-site
      target-controlled infusion (TCI), and the desflurane group received desflurane
      inhalation and remifentanil using effect-site TCI. We assessed quality of
      recovery at 6 hours after surgery through interviews using the QoR-40
      questionnaire. We also collected data related to recovery and complications
      during emergence and recovery period. RESULTS: The median of QoR-40 score on the
      day of surgery was significantly higher in the propofol group than that in the
      desflurane group (181.0 vs 169.5, respectively; P = .033). In particular,
      propofol group had significantly higher scores for physical comfort and physical
      independence dimensions. The amount of remifentanil administered was
      significantly higher, and the emergence time was significantly longer in propofol
      group. However, there were no significant differences in other complications
      between the 2 groups. CONCLUSIONS: Propofol total intravenous anesthesia provided
      significantly better quality of recovery on the day of surgery than desflurane
      inhalation anesthesia.

PMID- 30290668
TI  - Primary total knee arthroplasty for complex supracondylar femoral fractures in
      patients with knee arthritis: A retrospective study of a patient cohort.
AB  - When elder arthritis patients suffered from complex supracondylar femoral
      fractures, their joints condition and general health condition elevate the
      difficulties in operation and post-surgical recovery.Here, we aimed to simplify
      the operation procedure by using one-step Total Knee Arthroplasty (TKA) with a
      stemmed femoral implant. We also investigated if this method could improve the
      patients' experience after the operation. The surgery including femoral osteotomy
      and implantation was performed on all fourteen patients by the same orthopedic
      specialist. The patients' hospitalization time was recorded. The recovery of knee
      function and patient satisfaction was evaluated by a systematic follow-up with
      average time 38 months, up to 5 5 years, using Hospital for Special Surgery (HSS)
      knee scores, the range of motion (ROM), anteroposterior and lateral radiography,
      and Visual Analog Scale (VAS) scores. The average of hospitalization days was 16
      days. No angular deformity, malunion, or shortening were found at radiography.The
      average ROM was 105.2 degrees  at the end of the follow-up period. The knees in
      all the patients show adequate stability. All patients had returned to their
      former daily activities. Seventeen out of 24 patients were satisfied with the
      outcome of the surgery.The usage of TKA with a stemmed femoral implant is a
      reasonable method for elderly patients suffering from supracondylar femoral
      fractures and concomitant knee arthritis.

PMID- 30290669
TI  - Association of human leukocyte antigen alleles and supertypes with immunogenicity
      of oral rotavirus vaccine given to infants in China.
AB  - Rotavirus (RV) vaccines show distinct immunogenicity in dozens of clinical
      trials, which is associated with multiple host and environmental factors.
      Previous research has demonstrated that the highly polymorphic human leukocyte
      antigen (HLA) system plays an essential role in regulating immune response to a
      variety of vaccines. This study aims to investigate the relationship between HLA
      polymorphisms and immunogenicity of RV vaccine.A nested case-control study was
      carried out among infants enrolled in phase III clinical trial of trivalent human
      lamb reassortant vaccine (RV3) in Henan province, China. Serum RV specific
      immunoglobulin A (RV-IgA) was detected before and after a 3-dose vaccination
      series, followed by calculation of seroconversion rates. Seroconversion was
      defined as a 4-fold or greater increase in RV-IgA titers between pre-vaccination
      and 1-month post-dose 3 vaccination. The infants who seroconverted were defined
      as responders, and the others without seroconversion were considered as non
      responders. Their HLA genotypes were obtained by using the sequence-based typing
      method. The HLA allele and supertype frequencies of 2 groups were analyzed
      statistically.Eighty-three of 133 infants seroconverted after vaccination. Twenty
      one HLA-A, 45 HLA-B, 24 HLA-Cw, 29 HLA-DRB1 and 16 HLA-DQB1 distinct alleles were
      detected. The frequency of HLA-B4001 (corrected P = .01, adjusted OR = 0.152, 95%
      CI = 0.048-0.475) in non-responder group was significantly higher than that in
      responder group. Furthermore, significant association was found between HLA-B44
      supertype (corrected P = .02, adjusted OR = 0.414, 95% CI = 0.225-0.763) and RV
      non-response.Certain HLA allele (HLA-B4001) and supertype (HLA-B44) are
      potentially associated with non-response after immunization with the novel RV3
      vaccine in Chinese infants.

PMID- 30290670
TI  - No associations exists between red blood cell distribution width and serum uric
      acid in both sexes.
AB  - The aim of this study was to determine whether there was a significant
      association between red blood cell distribution width (RDW) and uric acid (UA) in
      a large Chinese population.This was a cross-sectional study with an enrollment of
      80,298 ostensibly healthy participants (48,971 males, 31,327 females) during the
      period from 2011 to 2015. In the study, database was grouped by sex and the
      association between RDW and UA was analyzed by quartiles of RDW.UA values between
      different sexes and RDW subgroups were analyzed by 2-way analysis of variance and
      Bonferroni t tests. Prevalence of hyperuricemia in different sexes was
      calculated. The relationship between risks of hyperuricemia and RDW level was
      analyzed by binary logistic regression with or without adjustment for age and
      body mass index.UA values were not all the same between different sexes and RDW
      subgroups. Males had significantly higher hyperuricemia prevalence than females
      (20.00% vs 6.48%, P < .01). In addition, hyperuricemia prevalence in males
      decreased slightly across RDW quartiles, but was stable in females. No
      significant association between hyperuricemia risk and RDW was found in both
      sexes according to the results of multivariate logistic regression analysis.
      Similarly, negative results were also observed in multivariate linear analysis
      when both RDW and UA were considered as continuous variable.We could not find any
      significant relationship between RDW and UA in both sexes.

PMID- 30290672
TI  - A large retroperitoneal lipoblastoma: A case report and literature review.
AB  - INTRODUCTION: Lipoblastoma is a rare benign soft tissue tumor that occurs most
      commonly in infants and children. However, retroperitoneal lipoblastomas are
      rare, occurring in <5% of cases. We report a case of large retroperitoneal
      lipoblastoma and the largest collection of known retroperitoneal lipoblastomas in
      children in the literature. CASE PRESENTATION: A 3-year-old girl presented with
      left abdominal mass. Magnetic resonance imaging (MRI) revealed a soft tissue mass
      measuring 12 * 8 * 6 cm in the retroperitoneal region. The mass had a clearly
      defined margin and a reticular pattern with an interposing fat component. Based
      on these findings, the mass was suspected to be a soft-tissue tumor, most likely
      lipoblastoma.Laparotomy with resection of the retroperitoneal mass was performed.
      The tumor was easily dissected from the retroperitoneal space without injury to
      surrounding structure.A histopathological examination demonstrated the mature
      proliferation of adipocytes and spindle-shaped cells separated by fibrovascular
      septa accompanied by myxoid changes. The cells were separated into lobules by
      septa, and areas of immature adipocytes showing a signet-ring or multivacuolar
      appearance were present at the periphery. Histopathological diagnosis was
      lipoblastoma. Follow-up at 6 months revealed no evidence of recurrence.
      CONCLUSION: Retroperitoneal lipoblastoma is rare and tends to be large in size
      when diagnosed at presentation. Complete resection should not be delayed, as
      impingement on the surrounding structures is imminent.

PMID- 30290671
TI  - Curative resolution of chronic thromboembolic pulmonary hypertension with
      pulmonary thromboendarterectomy in primary antiphospholipid syndrome: A case
      report.
AB  - RATIONALE: Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe
      complication of antiphospholipid syndrome (APS). Once diagnosed, the
      recommendation for the treatment of CTEPH is long-term anticoagulation and
      pulmonary thromboendarterectomy (PTE). However, cardiac surgeons apply PTE
      cautiously for these patients, as there is an increased risk of perioperative
      complications. Here, we present the curative case of a patient with severe APS
      associated CTEPH treated with PTE. PATIENT CONCERNS: A 29-year-old man presented
      with chest pain, decreased exercise capacity, dyspnoea, and haemoptysis.
      DIAGNOSES: He was triple positive for antiphospholipid antibodies. Computed
      tomography pulmonary angiography revealed multiple, recurrent pulmonary embolisms
      and complete obstruction of the left pulmonary artery. He was diagnosed with APS
      and CTEPH. INTERVENTIONS: After balancing the risk of thrombosis and haemorrhage,
      the patient underwent PTE. OUTCOMES: The patient experienced symptom relief after
      PTE, and electrocardiography at a six-month follow-up showed a recovery of
      cardiac structure and pulmonary arterial pressure. LESSONS: After evaluating the
      thrombosis risk at an experienced treatment centre and the application of
      standard anticoagulation treatment, PTE may be a curative resolution for APS
      associated CTEPH.

PMID- 30290673
TI  - Short bowel syndrome caused by laparoscopic loop enterostomy of the jejunum in an
      adult with undiagnosed intestinal malrotation: A case report.
AB  - RATIONALE: Failure to recognize intestinal malrotation in adults can cause
      complications during surgeries, especially those with a limited operative field.
      We report a case of short bowel syndrome caused by mistaken creation of a loop
      enterostomy in the jejunum due to undiagnosed intestinal malrotation. PATIENT
      CONCERNS: A 72-year-old man underwent a laparoscopic right hemicolectomy and
      ileocolostomy because of complicated diverticulitis. Six days after the surgery,
      he received laparoscopic exploration because of anastomotic leak, and a
      laparoscopic loop ileostomy was also performed as a protective diversion stoma.
      One month after surgery, he complained of severe diarrhea from the enterostomy
      after food and water intake. An upper gastrointestinal and small bowel series
      revealed that the duodenojejunal junction (DJJ) did not cross the midline and
      there was a short distance between the DJJ and the enterostomy in the right lower
      quadrant. DIAGNOSES: Short bowel syndrome caused by mistaken creation of a loop
      enterostomy in the jejunum due to undiagnosed intestinal malrotation.
      INTERVENTIONS: Total parental nutrition was used and the loop enterostomy was
      closed 3 months after the initial surgery. OUTCOMES: The patient was discharged
      uneventfully 2 weeks after the loop enterostomy. LESSONS: Intestinal malrotation
      in adults is often encountered during routine radiological examinations. However,
      it may cause complications during surgery if ignored. Radiologists should keep in
      mind that complications may occur if a complete presurgical evaluation of
      intestinal malrotation is not performed, and surgeons should take caution when
      performing surgeries, especially those with a limited operative field.

PMID- 30290674
TI  - Pleural effusion resulting from bronchial tuberculosis: A case report.
AB  - RATIONALE: The clinical manifestations in patients with bronchial tuberculosis
      (BTB) are nonspecific and may pose a great diagnostic challenge. PATIENT
      CONCERNS: Here we describe the case of a 57-year-old man presented with right
      chest pain, chest tightness, and discomfort for 2 days. DIAGNOSIS: Bronchoscopic
      biopsy was performed which revealed subepithelial and epithelioid cell granuloma
      of Langerhans cell structure. The definitive diagnosis was BTB with pleural
      effusion. INTERVENTIONS: Treatment with a quadruple combinational antituberculous
      therapy was initiated. OUTCOMES: Two months later, the patient's chest distress
      and discomfort significantly decreased. Repeat chest radiograph revealed that the
      pleural fluid had been absorbed. The patient recovered after 15 months of
      antituberculosis treatment. LESSONS: The patient exemplifies the difficulty of
      diagnosing BTB, particularly the low reliability of imaging modalities. The
      diagnosis of BTB currently relies on bronchoscopy as well as bacteriological or
      pathological evidence. This report will help to lower the incidences of
      misdiagnosis of this disease.

PMID- 30290675
TI  - Evidence supporting FDA approval and CMS national coverage determinations for
      novel medical products, 2005 through 2016: A cross-sectional study.
AB  - Food and Drug Administration (FDA) and Centers for Medicare and Medicaid Services
      (CMS) rely on evidence from clinical trials when approving a therapeutic for
      marketing and insurance coverage in the US, respectively. No study has compared
      the quality and quantity of evidence examined by these agencies.To characterize
      evidence used by FDA and CMS to support marketing approval and National Coverage
      Determinations (NCDs), respectively, of novel therapeutics reviewed for CMS
      coverage from 2005 through 2016.A cross-sectional study of clinical trials
      described in FDA approval documents and CMS NCD memoranda. We compared the number
      of clinical trials used by each agency as well as the following characteristics
      among original clinical trials: study size, randomization, double-blinding, and
      control arm.Twelve medical products met our inclusion criteria. FDA approvals of
      these products were based on 22 pivotal trials. CMS NCDs were based on 27
      original clinical trials; 14 clinical trials were used by both agencies. Between
      FDA pivotal and CMS original clinical trials, there was no significant difference
      in study size (P = .53), use of randomization (P = .75), double-blinding (P =
      .55), or control arm (P = .54). There was no statistically significant difference
      in median age between participants in trials reviewed by CMS versus those
      reviewed by FDA (62 vs 59 years, P = .26). The median time from FDA approval to
      publication of CMS NCD memorandum was 17 (interquartile range, 13-36) months.FDA
      approvals and CMS NCDs are based on a similar number and quality of trials,
      although trial participants are not reflective of the Medicare population, and
      the process of finalizing coverage determinations requires an additional 17
      months.

PMID- 30290676
TI  - Case report of mixed-type autoimmune hemolytic anemia in a patient with relapsing
      polychondritis.
AB  - RATIONALE: Relapsing polychondritis (RP) is a rare autoimmune-related disease and
      may be associated with other autoimmune diseases. PATIENT CONCERNS: Here we
      reported a case of RP patients with mixed-type AIHA. The patient was diagnosed
      with RP in March 2008 which was treated and the patient was in stable condition.
      Laboratory data revealed progressive decrease in hemoglobin during her
      hospitalization due to pulmonary infection in 2016. Positive Coombs' test and
      moderate titer of anti-cold agglutinin was detected. DIAGNOSIS: Mixed-type AIHA
      was diagnosed as a comorbidity in this case given the circumstance that her RP
      was stable and low-dose oral corticosteroids was enough to maintain remission.
      INTERVENTIONS: The patient was treated with intravenous immunoglobulin and
      steroids. OUTCOMES: The patient's body temperature dropped and hemoglobin levels
      rose in 2 weeks. LESSONS: Reports of RP patients with autoimmune hemolytic anemia
      (AIHA) are extremely rare and cases with the mixed-type AIHA has not been
      reported. Here we describe a case of RP with mixed-type AIHA which was considered
      as a comorbidity rather than a complication.

PMID- 30290677
TI  - Investigation of rare earth elements in urine and drinking water of children in
      mining area.
AB  - To compare the contents of rare earth elements in urine and drinking water of
      children in the mining and control areas and evaluate the health risk of children
      in the mining area.Urine and drinking water of 128 children in the mining area
      and 125 children in the control area were collected from June to July 2015. The
      contents of rare earth elements were determined using inductively coupled plasma
      mass spectrometry.The detection rates of rare earth elements, including yttrium
      (Y), lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), and samarium
      (Sm), in the urine of children in the exposed group were all 100%, except for
      samarium (98%); the rates in the control group were 85.7%, 100%, 100%, 98%, 98%,
      and 59.2%, respectively, and the remaining elements were not detectable. The
      concentrations of Y, La, Ce, Pr, Nd, and Sm in the urine of children in the
      exposed group were significantly higher than that in the control group (P < .01).
      In addition, the composition ratio of lanthanum was higher than that in the
      control group. The detection rates of lanthanum and Ce in the drinking water of
      children in the exposed group were 1.44% and 0.72%, respectively. The others were
      not detectable; the rates in the control group were all 0%.The pollution caused
      by the presence of Y, La, Ce, Pr, Nd, and Sm in the mining area might affect the
      health of children in the area, but drinking water might not be the cause.

PMID- 30290678
TI  - Analysis of the risk factor for the poor prognosis of localized neuroblastoma
      after the surgical.
AB  - Neuroblastoma is a unique malignancy in infants often presenting with either
      localized or metastatic disease. The study was carried out to explore the risk
      stratification of the poor prognosis for patients underwent surgical treatment.60
      patients diagnosed with neuroblastoma were primarily enrolled in the study from
      April 2008 to April 2016. All the patients underwent surgical treatment and
      received 5-year follow-up. Clinical variables, including age, International
      Neuroblastoma Staging System (INSS) stage, tumor size and site, histology, and
      MYCN status were retrospectively analyzed, and EFS was chosen as the endpoint.The
      median age of patients was 8.2 months and average follow-up period was 40.2 +/-
      8.6 months. Among 60 patients, complete remission was achieved in 35 patients and
      partial remission in 14 subjects. Poor prognosis including patient death and
      tumor progression were overserved in 11 patients. Cox multifactor regression
      analysis revealed that age, histology and MYCN status had significant prognostic
      effect on event-free survival (EFS) rate for neuroblastoma patients underwent
      surgical treatment.In our study, we identified a series of prognostic factors
      including age, histology, and MYCN status predicting the prognosis of
      neuroblastoma patients after surgical treatment.

PMID- 30290679
TI  - Infliximab as an alternative therapy for refractory adult onset Kawasaki disease:
      A case report.
AB  - RATIONALE: Kawasaki disease (KD) is an acute febrile illness predominantly
      affecting children less than 5 years of age and characterized by systemic
      inflammation in all medium-sized arteries. Adult-onset KD (AKD) is rare with only
      105 case reports published. Recently, the efficacy of infliximab (IFX) for
      patients with refractory KD has been demonstrated. PATIENT CONCERNS: A previously
      healthy 24-year-old man was admitted because of a persistent fever, and elevated
      serum level of AST, ALT, LDH, and CRP. DIAGNOSIS: The patients met the diagnostic
      criteria for KD based on the findings of persistent fever, polymorphous
      exanthema, unilateral cervical lymphadenopathy, non-purulent palpebral
      conjunctivitis and membranous desquamation. Echocardiogram revealed the
      dilatation at the proximal sites of the right coronary artery (7.9 mm) and left
      anterior descending artery (5 mm). The patient was treated with high-dose
      intravenous immunoglobulin (1 g/kg/day for 2 days) and ASA (100 mg daily).
      However, his fever and arthralgia persisted. INTERVENTIONS: He was administered
      single 5 mg/kg doses of IFX. OUTCOMES: He became afebrile the next day and his
      arthralgia improved. LESSONS: We report the first case of administration of IFX
      in a patient with AKD refractory to intravenous immunoglobulin (IVIG), and
      successful reduction of systemic inflammation. However, the effectiveness of IFX
      in the regression of coronary artery aneurysm remains to be determined.

PMID- 30290681
TI  - Isolated extradural Rosai-Dorfman disease causing the spinal cord compression: A
      case report.
AB  - RATIONALE: Rosai-Dorfman disease (RDD) is a rare benign histiocytic disease that
      is commonly characterized by massive painless cervical lymphadenopathy and
      systemic manifestations. Isolated extranodal involvement, especially spinal
      involvement, is extremely rare. PATIENT CONCERNS: A 28-year-old man presented
      with intermittent dorsodynia and bilateral lower-limb weakness and numbness. A
      magnetic resonance scan (MRI) showed an extradural lesion of the T6-T9 thoracic
      spine that lead to cord compression. DIAGNOSES: Histopathological findings showed
      distinctive emperipolesis and immunohistochemistry results that were positive for
      cluster of differentiation CD68 and S100. Therefore, we diagnosed the Rosai
      Dorfman disease. INTERVENTIONS: we performed a nearly total surgical resection
      and a limited T6-T9 laminectomy. OUTCOMES: Postoperatively, the patient's
      symptoms were partially relieved and experienced no recurrence during the 6-month
      follow-up. The preoperative diagnosis of isolated spinal RDD still remains
      challenging. LESSONS: Thus, we should consider RDD in the differential diagnosis
      of the central nervous system. Besides surgical resection, the treatment also
      included radiation, chemotherapy or monoclonal antibodies. However, the optimal
      treatment remains controversial. Therefore, we should exert all our energies on
      the exploration of etiology and adjuvant therapy for this disease.

PMID- 30290680
TI  - Rationale and design of a randomized trial of early intensive blood pressure
      lowering on cerebral perfusion parameters in thrombolysed acute ischemic stroke
      patients.
AB  - BACKGROUND AND RATIONALE: Uncertainty persists over the optimal management of
      blood pressure (BP) in the early phase of acute ischemic stroke (AIS). This study
      aims to determine the safety and effects of intensive BP lowering on cerebral
      blood flow (CBF) and functional in AIS patients treated with intravenous
      thrombolysis. METHODS: In a randomized controlled trial, 54 thrombolysed AIS
      patients with a systolic BP of 160 to 180 mm Hg will be randomized to early
      intensive BP lowering (systolic target range 140-160 mm Hg) or guideline-based BP
      management (systolic range 160-180 mm Hg) during first 72-hours using primarily
      intravenous labetalol. We hypothesize that early intensive BP lowering will not
      reduce CBF by 20% and/or increase the volume of hypoperfused tissue by >20% on
      computed tomographic perfusion. Clinical outcome will be assessed using a
      dichotomized modified Rankin scale (scores 0-1 as excellent outcome vs scores 2-6
      as dead or dependent) at 90 days. Other outcome would be symptomatic
      intracerebral hemorrhage. The trial is registered at ClinicalTrials.gov,
      NCT03443596. CONCLUSION: This randomized study will provide important information
      about the physiological effects of BP reduction on cerebral perfusion after
      intravenous thrombolysis in AIS.

PMID- 30290682
TI  - Progression of aggressive vertebral hemangiomas during pregnancy: Three case
      reports and literature review.
AB  - RATIONALE: Vertebral hemangiomas (VHs), one of the most common benign tumors of
      the spine, can be aggressive, which is a rare condition and causes neurological
      deficits. Pregnancy is related to the worsening of aggressive VHs. The diagnosis
      and treatment of aggressive VHs remain challenging, especially for pregnant
      cases. PATIENT CONCERNS: We report 3 cases of aggressive VH in women who
      developed progressive neurological deficits during pregnancy among 95 patients
      treated for aggressive VH in our hospital in the past 15 years. DIAGNOSES AND
      INTERVENTIONS: All 3 patients experienced progressive deterioration of
      neurological function and pain at 13, 28, and 41 weeks' gestation. On
      radiological examination, VHs were the suspected radiological diagnoses in 2
      patients; 1 patient was preoperatively misdiagnosed with a spinal metastatic
      tumor. All 3 patients underwent decompression surgery with intraoperative
      vertebroplasty and/or postoperative radiotherapy. The pathological diagnosis
      after surgery was all hemangiomas. OUTCOMES: In all 3 patients, there were no
      tumor recurrences, and neurological functions remained normal at the last follow
      up of 75, 38, and 15 months after the treatment, respectively. LESSONS: Pregnancy
      might lead to the onset of aggressive VHs. The diagnosis and treatment of VHs
      during pregnancy remain controversial due to concern for both maternal and fetal
      safety. Timely surgery could preserve neurological function. Decompression
      surgery by laminectomy followed by adjuvant therapies require less skill and have
      a shorter surgery time, and can be considered more appropriate for aggressive VHs
      with pregnancy.

PMID- 30290683
TI  - Ultrasonographic features of testicular metastasis from renal clear cell
      carcinoma that mimics a seminoma: A case report.
AB  - RATIONALE: Testicular metastases from renal cell carcinoma (RCC) are extremely
      rare. To the best of our knowledge, only 35 cases have been described in the
      literatures. PATIENT CONCERNS: A 64-year-old male presented to our urology clinic
      for a palpable painless mass on his right side of the scrotum by self-examination
      1 week ago, with a general abdominal ultrasonographic report showing a mass in
      his right kidney. DIAGNOSES AND INTERVENTIONS: Scrotal B-mode ultrasound revealed
      a 15 * 13 * 15 mm well-defined round homogenously hypoechoic nodule with a halo
      at the upper pole of the right testis. Color Doppler and spectral Doppler
      ultrasound detected abundant intranodular and perinodular blood flow signals
      including both arteries and veins. Malignancy was suspected. Abdominal contrast
      enhanced computed tomography identified an irregular tumor in the posterior side
      of the right kidney, highly suspicious for renal carcinoma. The patient received
      right radical nephrectomy and right partial orchiectomy. Histologically, the
      right renal mass was diagnosed as RCC, clear cell type, grade 2. As to the right
      testicular mass, a metastasis from renal clear cell carcinoma was confirmed.
      OUTCOMES: The patient has lived with no recurrence for at least 17 months without
      adjuvant therapy. LESSONS: In the case, we focus on the ultrasonographic features
      of the testicular metastasis from RCC. Ultrasound could provide initial and
      helpful information for diagnosis. When finding a mass in the testicle on the
      ultrasound, although most of them are primary, it is important to know whether
      the patient has tumor history from other parts of the body. A halo may be a
      special feature for metastases. Contrast-enhanced ultrasound (CEUS) and
      ultrasonic elastography could provide more information for differential
      diagnoses.

PMID- 30290684
TI  - Regaining body weight after weight reduction further increases pulse wave
      velocity in obese men with metabolic syndrome.
AB  - Subjects with metabolic syndrome (MetS) or obesity have worse arterial stiffness.
      However, there have been no studies addressing time-sequential changes in pulse
      wave velocity (PWV) after weight loss and then regaining weight in obese non
      diabetic men with MetS.We prospectively enrolled 40 obese, non-diabetic men with
      MetS undergoing a 3-month weight reduction program. Another 26 lean and healthy
      men were recruited for comparisons. Oral glucose tolerance test and brachial
      ankle (ba) PWV were assessed in study subjects. Eighteen obese non-diabetic MetS
      and 15 lean control subjects had follow-ups at the 60th month.The body weight of
      obese MetS decreased from 94.8 +/- 7.6 to 86.1 +/- 9.0 (N = 18, P < .001) after a
      3-month weight reduction program but regained gradually thereafter to 93.6 +/-
      11.6 kg at the 60th month (P < .001 versus 3rd month). baPWV decreased after
      weight loss slightly (P = .240) while weight regain significantly increased the
      baPWV (from 3rd month, 1358 +/- 168 to 60th month 1539 +/- 264 cm/sec, P < .001).
      Systolic and diastolic blood pressure increments correlated with the increment of
      baPWV after weight regain. At the 60th month, lean controls (N = 15) had
      increases in body weight while their baPWV increased non-significantly. The
      increments of baPWV after weight regain in obese MetS were significantly higher
      than the increment of baPWV in lean controls after weight gain.In conclusion,
      regaining body weight after weight reduction worsened arterial stiffness with
      significant increase of baPWV in obese non-diabetic MetS.

PMID- 30290685
TI  - Vitamin D supplementation to prevent vitamin D deficiency for children with
      epilepsy: Randomized pragmatic trial protocol.
AB  - BACKGROUND: Vitamin D deficiency is highly prevalent among children with
      epilepsy. Lack of high-quality evidence led to variability among scientific
      societies recommendations. Therefore, we aim to determine the efficacy of
      different common doses used in the pediatric practice to maintain optimal 25
      hydroxy vitamin D (25 [OH] vitamin D) level in children with epilepsy and normal
      baseline 25 (OH) vitamin D level over 6 months of supplementation. METHODS: This
      is a protocol for phase IV pragmatic randomized superiority controlled open-label
      trial at King Saud University Medical City in Riyadh. Children with epilepsy and
      receiving chronic antiepliptic medication and normal baseline 25 (OH) vitamin D
      level will be randomly assigned to receive Cholecalciferol 400 IU/day versus 1000
      IU/day for 6 months. Our primary outcome is the proportion of children with
      vitamin D insufficiency (25 (OH) vitamin D level < 75nmol/L) at 6 months.
      Secondary outcomes include seizure treatment failure, seizure frequency,
      parathyroid hormone (PTH) levels, bone mineral density, and safety. DISCUSSION:
      Our trial is set out to evaluate the efficacy of common different vitamin D
      maintenance doses on 25 (OH) vitamin D level, seizure control, and bone health
      for children with epilepsy. The results of our study will possibly help in
      shaping current vitamin D guidelines for vitamin D supplementation in children
      with epilepsy and provide a link between 25 (OH) vitamin D level and seizure
      control.

PMID- 30290686
TI  - Predictors of early weaning failure from mechanical ventilation in critically ill
      patients after emergency gastrointestinal surgery: A retrospective study.
AB  - Mechanical ventilation (MV) is the most common therapeutic modality used for
      critically ill patients. However, prolonged MV is associated with high morbidity
      and mortality. Therefore, it is important to avoid both premature extubation and
      unnecessary prolongation of MV. Although some studies have determined the
      predictors of early weaning success and failure, only a few have investigated
      these factors in critically ill surgical patients who require postoperative MV.
      The aim of this study was to evaluate predictors of early weaning failure from MV
      in critically ill patients who had undergone emergency gastrointestinal (GI)
      surgery.The medical records of 3327 adult patients who underwent emergency GI
      surgery between January 2007 and December 2016 were reviewed retrospectively.
      Clinical and laboratory parameters before surgery and within 2 days postsurgery
      were investigated.This study included 387 adult patients who required
      postoperative MV. A low platelet count (adjusted odds ratio [OR]: 0.995; 95%
      confidence interval [CI]: 0.991-1.000; P = .03), an elevated delta neutrophil
      index (DNI; adjusted OR: 1.025; 95% CI: 1.005-1.046; P = .016), a delayed
      spontaneous breathing trial (SBT; adjusted OR: 14.152; 95% CI: 6.571-30.483; P <
      .001), and the presence of postoperative shock (adjusted OR: 2.436; 95% CI: 1.138
      5.216; P = .022) were shown to predict early weaning failure from MV in the study
      population.Delayed SBT, a low platelet count, an elevated DNI, and the presence
      of postoperative shock are independent predictors of early weaning failure from
      MV in critically ill patients after emergency GI surgery.

PMID- 30290687
TI  - Complications of percutaneous liver biopsy in living donor liver transplantation:
      Two case reports.
AB  - RATIONALE: According to previously published studies, major complications arising
      from a percutaneous liver biopsy are rare and occur in less than 0.1% of cases.
      This report describes an approach to percutaneous liver biopsy that can help
      avoid damage to the liver in a living donor liver transplantation (LDLT) setting.
      PATIENT CONCERNS: Case 1: In the first case a donor percutaneous liver biopsy
      (PLB) of both lobes of the liver was performed for pre-LDLT evaluation. The
      ultrasonography (US)-guided epigastric right-angle approach and an automatic one
      handed cocking disposable 18G biopsy gun was used to puncture the left liver lobe
      to determine the presence of fatty liver. A penetrating liver injury occurred,
      accompanied by massive bloody ascites (about 700 cc) and subcapsular hematoma at
      the left lateral segment. The bleeding was managed by bi-polar coagulation during
      the transplant and the following liver donation procedure proceeded smoothly
      without any subsequent complications. Case 2: In the second case, selective right
      lobe PLB for clinical assessment after LDLT was performed in the recipient.
      Hemorrhagic shock occurred following a puncture of the right posterior branch of
      the right hepatic artery when using the biopsy-gun via the right lateral
      intercostal approach. DIAGNOSES: Extravasation was documented by angiography and
      emergent transhepatic arterial embolization was performed. INTERVENTION:
      Extravasation was documented by angiography and emergent transhepatic arterial
      embolization with glue:lipiodol (1:4) was performed to stop bleeding. OUTCOMES:
      The recipient survived after medical management. LESSONS: To prevent
      complications, the right-angle approach of PLB may be changed to an oblique angle
      using a one-fire biopsy-gun. Use of a manual Menghini's needle should be
      considered for left lobe liver biopsies. Since US-guided manual Menghini's needle
      for PLB can be observed with the needle tip inserted in the liver, needle
      mediated compromising of the major vessels or biliary tree can be prevented, and
      it does not penetrate the liver again. A superficial puncture less than 0.5 cm
      away from the liver surface should be made during right lobe liver biopsy. This
      approach can help to avoid damage to the hepatic artery.

PMID- 30290688
TI  - A low abundance of Bifidobacterium but not Lactobacillius in the feces of Chinese
      children with wheezing diseases.
AB  - BACKGROUND: The intestinal microbiota is linked with allergic reaction diseases.
      However, the difference in the fecal microbiota composition between sensitized
      wheezy and nonsensitized subjects in Chinese children remains unknown. The aim of
      this study was to quantitate the amounts of fecal microbiota in wheezy children,
      and to explore the correlation between fecal microbiota and serum Th1/Th2/Th17
      type cytokines and total IgE in these patients. METHODS: The amounts of
      Bifidobacterium and Lactobacillus were determined using a 16S-RNA real-time
      polymerase chain reaction (PCR) method in wheezy children (cases) and nonwheezy
      controls. Serum Th1/Th2/Th17-type cytokines levels were measured using flow a
      cytometric bead array assay. In addition, the concentrations of total serum IgE
      was also determined. RESULTS: In comparison with that in the healthy control
      (HC), significantly lower abundance of Bifidobacterium and lower levels of Th1
      cytokines (IFN-gamma and TNF-alpha), but higher levels of Th2-type cytokines (IL
      4, IL-5) and Th17-type (IL-17A) cytokine were detected in children with
      bronchiolitis and asthma. But there was no significant difference in the amounts
      of Lactobacillus. Interestingly, the amounts of fecal Bifidobacterium were
      correlated positively with serum Th1 cytokines IFN-gamma, and correlated
      negatively with serum Th17 cytokines IL-17A, Th2 cytokines IL-4 and serum total
      IgE in these patients. CONCLUSIONS: Our findings demonstrated that lower quantity
      of Bifidobacterium, but not Lactobacillus, may be correlated with asthma and
      bronchiolitis in chinese children. These results also may provide guidance in
      choosing the proper probiotics for wheezing children.

PMID- 30290689
TI  - Supra-inguinal fascia iliaca block under ultrasound guidance for perioperative
      analgesia during bipolar hip arthroplasty in a patient with severe cardiovascular
      compromise: A case report.
AB  - RATIONALE: The relief of selective hip pain may be difficult to attain.
      Therefore, a deep nerve block such as epidural anesthesia or lumbar plexus nerve
      block is required. However, deep nerve blocks may not be possible in patients
      with complications, including severe cardiovascular disease. PATIENTS CONCERNS:
      The patient in our report had coronary stents inserted previously and required
      continuous anticoagulant therapy owing to severe heart failure. DIAGNOSIS:
      Bipolar hip arthroplasty was required in our patient because of a fracture of the
      neck of femur on the left side. INTERVENTIONS: We decided to perform the surgery
      using a fascia iliaca block (block of the femoral and the lateral femoral
      cutaneous nerves) by the suprainguinal approach. The fascia iliaca nerve block
      was performed under ultrasound guidance, using 20 mL of levobupivacaine.
      OUTCOMES: The surgery was performed successfully with adequate sensory block
      around the hip region. LESSONS: Ultrasound-guided fascia iliaca nerve block by
      the supra-inguinal approach may be an effective anesthetic technique for patients
      undergoing surgery for fracture of the neck of femur.

PMID- 30290691
TI  - Management of primary biliary cholangitis: the importance to identify patients
      non-responders to standard treatment.

PMID- 30290690
TI  - Drug dependence in patients with chronic pain: A retrospective study.
AB  - Drug dependence, which can exist concurrently with chronic pain, is seen as one
      of the major causes of rapidly increasing medical expenses. However, drug
      dependence in patients with chronic pain has not been evaluated. The aim of this
      study was to identify the risk factors for drug dependence in patients with
      chronic noncancer pain.This retrospective study included 151 patients with
      chronic noncancer pain (43 males, 108 females; mean age, 72 years). Low back pain
      (LBP) occurred in 96 patients, whereas 22 had shoulder pain, 8 had hip pain, and
      77 had knee pain. Patients were divided into drug dependence and nondrug
      dependence groups based on the Severity of Dependence Scale (SDS) scores.
      Patients with SDS scores >=5 and <5 were classified into drug dependence and
      nondrug dependence groups, respectively. All patients completed self-report
      questionnaires. Factors that predict drug dependence were identified by
      performing univariate and multivariate analyses.Sixty (40%) of the 151 patients
      met the SDS criteria for drug dependence. Significant differences were found
      between patients with and without drug dependence for the LBP, hip pain, number
      of medications, and for the Numerical Rating Scale, Pain Disability Assessment
      Scale (PDAS), Hospital Anxiety and Depression Scale, and Pain Catastrophizing
      Scale (PCS) scores. Multiple regression analysis identified LBP, hip pain, PCS,
      and PDAS scores as factors related to drug dependence in patients with chronic
      noncancer pain.Drug dependence tends to differ in patients based on the location
      of their chronic pain. Pain catastrophizing and disability indicated a greater
      tendency for drug dependence. Thus, PCS and PDAS scores are useful screening
      tools for predicting drug dependence in patients with chronic pain.

PMID- 30290692
TI  - The main predictors of the enlargement of ascending aorta in Turner syndrome: a
      cross-sectional contrast-enhanced magnetic resonance angiography study.
AB  - AIM: To identify the main predictors of the enlargement of ascending aorta and to
      assess the possible relation between reduced bone mineral density and a diameter
      of ascending aorta in the specific Turner syndrome (TS) population. METHODS: 50
      adult females diagnosed with TS have been enrolled into the cross-sectional
      study. Dimensions of ascending aorta have been measured in four positions using
      thoracic magnetic resonance imaging, aortic size index (ASI) has been calculated.
      BMD has been assessed on dual - energy - X ray absorptiometry (DXA) in 1 - 4
      lumbar vertebrae and neck of the femur. According to Z score on DXA two groups
      have been formed: a group of patients with normal BMD and a group with reduced
      BMD. Metabolic parameters and the measurements of ascending aorta have been
      compared between the two groups. RESULTS: Extremely high rate of the dilatation
      of the root of aorta (up to 50 %) was identified in this study. The larger ASI
      has been found in patients with reduced BMD, negative relation between BMD and
      ASI has been identified, although after the adjustment for SHRT this correlation
      remained insignificant. In the multivariate analysis, the main factors affecting
      ASI were age, body surface area and bicuspid aortic valve. CONCLUSIONS: The main
      factors associated with the enlargement of ascending aorta in Turner syndrome
      were age, body surface area and bicuspid aortic valve, the relation between
      diameter of ascending aorta and bone mineral density was not identified.

PMID- 30290693
TI  - The role of hybrid operating room in emergency microsurgery for massive
      intracranial hematoma arising from vascular malformations.

PMID- 30290694
TI  - A giant calcific aneurysm of an aplastic middle cerebral artery in an infant:
      pathophysiological description with embryological hypothesis.

PMID- 30290695
TI  - Long-term fate of C3-7 arthrodesis: 4-level ACDF versus Cervical Laminectomy and
      Fusion.
AB  - INTRODUCTION: Cervical spondylotic myelopathy (CSM) most commonly occurs at the
      C3-7 levels and is successfully treated by multilevel anterior cervical
      discectomy and fusion (ACDF) or cervical laminectomy and fusion (CLF), but no
      procedure has clearly demonstrated superiority. Most prior investigations
      comparing approaches are limited by marked heterogeneity in the composition of
      the study groups. This investigation compares ACDF versus CLF surgery
      specifically at C3-7 in terms of long-term neurological outcome and the fate of
      the adjacent levels. METHODS: Over a twelve-year period, surgeries to treat CSM
      at C3-7 by ACDF or CLF were retrospectively reviewed. Demographic/clinical data
      were recorded, pre/post- operative modified Japanese orthopedic association
      scores (mJOA) were calculated, and any complications were noted. RESULTS: Of 781
      cervical surgery patients, 15 underwent C3-7 ACDF and 49 CLF. There were no
      differences in patient characteristics or pre/postoperative mJOA scores. Mean
      follow-up was 52 and 44 months for the anterior and posterior groups
      respectively. A complication occurred in 3/15 (21%) of the anterior and 14/49
      (28%) of the posterior group. No infections occurred in ACDF patients, but there
      were three in CLF patients. Pseudoarthrosis occurred in two ACDF patients,
      neither associated with symptoms. Four in the CLF group had asymptomatic
      pseudoarthroses; two others needed reoperation for kyphosis at the inferior
      level. CONCLUSIONS: Long-term neurological improvement occurs following C3-7 ACDF
      and CLF to a similar degree. While not statistically significant, fewer
      complications, were seen following ACDF. The absence of symptomatic adjacent
      segment degeneration (ASD) following ACDF in this series raises a question for
      further study whether the statistical likelihood of ASD changes once the C3-7
      levels are already fused.

PMID- 30290696
TI  - Preoperative surgical planning of glioma. Limitations and reliability of fMRI and
      DTI tractography.
AB  - Brain mapping techniques (intraoperative neurophysiology and intraoperative
      neuropsychology) represent the gold standard in glioma surgery; these techniques
      have been proven to be the gold standard in glioma resection. From the
      introduction of MRI in clinical routine, several advanced applications have been
      developed like functional MRI and tractography based on diffusion imaging. Both
      techniques have application in glioma surgery. The fMRI allows to identify
      cortical areas related to a specific function, DTI allow to reconstruct a model
      of the sub-cortical connectivity. This paper describes the clinical application
      of fMRI and DTI tractography, enlightening sensitivity and specificity in
      comparison to gold standard and underlining their limitation in surgical decision
      making.

PMID- 30290697
TI  - Fuel Use Trends for Boiling Water in Rural China (1992-2012) and Environmental
      Health Implications: A National Cross-Sectional Study.
AB  - Survey data from a comprehensive national survey of ~34 000 households were
      analyzed for the mix status and transition trajectory of energy for boiling water
      in rural Chinese households from 1992 to 2012. In 1992, ~6% of households
      reported using electricity, biogas, or liquefied petroleum gas (LPG) to boil
      drinking water; in 2012, the proportion was ~60%. Income per capita appeared most
      strongly associated with this transition toward electricity and other clean
      fuels. Median annual incomes for households using biomass fuels, electric
      kettles, and LPG were RMB 15 000, 28 000, and 30 000, respectively. Overall, the
      transition was most pronounced in eastern China, a region which experienced
      relatively higher rates of economic growth over the same 20-year period. Energy
      type preferences appear to be highly dependent on fuel accessibility such that
      coal and straw usage was higher in provinces with higher coal and grain
      production. These trends suggest that electric kettle use would likely increase
      from ~29% (2012) to ~60% by 2030, at which point <5% of rural households would be
      expected to boil with solid fuels. Recent evidence suggests that this transition
      could contribute to reductions in water-related gastrointestinal illness as well
      as reductions in air pollutant emissions in rural China.

PMID- 30290698
TI  - Telemedicine in remote Australia: The Royal Flying Doctor Service (RFDS) Medical
      Chest Program as a marker of remote health.
AB  - INTRODUCTION: Remote communities across Australia lack the ready access to
      medical care generally afforded to metropolitan populations. The Royal Flying
      Doctor Service (RFDS) medical chest program provides medical resources to these
      communities allowing medications to be dispensed in conjunction with a telehealth
      consulting service. More than 3000 medical chests are located throughout
      Australia and each year the Queensland RFDS conducts approximately 20 000
      telehealth consultations. The aim of this study was to review the use of the
      medical chest model within the state of Queensland and to analyse changes in the
      medical chest program from 10 years earlier to evaluate the changing healthcare
      needs of remote Australian populations. METHODS: All telehealth consultations and
      items dispensed from the medical chests were reviewed over a 1-year period from 1
      July 2013 and 30 June 2014. Items dispensed were categorised and compared to
      those in 2005-06 in absolute terms by one-way ANOVA and proportionately by chi2
      with Fisher's exact test. Consultations using the medical chest were categorised
      and compared to those in 2005-06 by chi2 with Fisher's exact test. RESULTS: The
      number of telehealth consultations conducted in 2013-14 (N=20 707) was not
      different to the number conducted in 2005-06 (N=21 470). Fewer items were
      dispensed from the medical chests in 2013-14 (3936 total items) than in 2005-06
      (8607 total items; p<0.0001). In the specific categories of 'burns and other
      dressings' and 'antihistamines', the number of individual items dispensed
      increased. Resources from the medical chest were used more for genitourinary
      system consultations and less for consultations involving specific infectious
      diseases; the circulation, respiratory and abdominal systems; skin diseases;
      injury; symptoms without a diagnosis; and following other contact with a health
      service. CONCLUSIONS: The medical chests remain a vital tool for medical care of
      remote populations and the need for telehealth medical advice remains unchanged,
      although fewer items are being dispensed. The use of the medical chest for each
      diagnostic category of consultation has shown some variation over the past 10
      years, reflective of changing patterns of accident, injury and disease.

PMID- 30290699
TI  - Contextual factors and health service performance from the perspective of the
      provincial health administrators in Papua New Guinea.
AB  - INTRODUCTION: The Rural Primary Health Services Delivery Project aims to improve
      the quality and coverage of health services to rural populations in Papua New
      Guinea. There are limitations in measuring performance of such projects through
      analysis of health information system data alone due to data quality issues and a
      multitude of unmeasured factors that affect performance. A mixed methods study
      was undertaken to understand the contextual factors that affect health service
      performance. METHODS: A performance assessment framework was developed including
      service delivery indicators derived from the National Health Information System.
      Prior to implementation, a baseline analysis of the indicators was undertaken.
      Subsequently, semi-structured interviews were conducted with health
      administrators, in which they were asked about factors they perceived to
      influence health facility performance. During the interviews, key informants were
      provided with health indicators for their province and asked to interpret the
      performance of facilities. Interviews were transcribed and inductive thematic
      analysis performed. RESULTS: Performance indicators varied greatly within and
      between districts. Key informants cited a number of reasons for this variation.
      Health facilities accessible by road in urban areas, with competent and/or higher
      level staff and health services operated by churches or private companies, were
      cited as contributors to high performance. For high performing districts, key
      informants also discussed use of health information, planning and targeted
      strategies to improve performance. Inadequate numbers of staff, poorly skilled
      staff, funding delays and challenging geography were major contributors noted for
      poor performance. CONCLUSION: Analysis of quantitative indicators needs to be
      performed at health facility level in order to understand district level
      performance. Interpretation of performance through key informant interviews
      provided useful insight into previously undocumented contextual factors affecting
      health delivery performance. The sequential explanatory mixed methods design
      could be applied to evaluations of other health service delivery programs in
      similar contexts.

PMID- 30290700
TI  - Update on: proteome analysis in thyroid pathology - part II: overview of
      technical and clinical enhancement of proteomic investigation of the thyroid
      lesions.
AB  - INTRODUCTION: An accurate diagnostic classification of thyroid lesions remains an
      important clinical aspect that needs to be addressed in order to avoid
      'diagnostic' thyroidectomies. Among the several 'omics' techniques, proteomics is
      playing a pivotal role in the search for diagnostic markers. In recent years,
      different approaches have been used, taking advantage of the technical
      improvements related to mass spectrometry that have occurred. Areas covered: The
      review provides an update of the recent findings in diagnostic classification, in
      genetic definition and in the investigation of thyroid lesions based on different
      proteomics approaches and on different type of specimens: cytological, surgical
      and biofluid samples. A brief section will discuss how these findings can be
      integrated with those obtained by metabolomics investigations. Expert commentary:
      Among the several proteomics approaches able to deepen our knowledge of the
      molecular alterations of the different thyroid lesions, MALDI-MSI is strongly
      emerging above all. In fact, MS-imaging has also been demonstrated to be capable
      of distinguishing thyroid lesions, based on their different molecular signatures,
      using cytological specimens. The possibility to use the material obtained by the
      fine needle aspiration makes MALDI-MSI a highly promising technology that could
      be implemented into the clinical and pathological units.

PMID- 30290701
TI  - Increased use of illicit drugs in a Dutch cluster headache population.
AB  - Introduction Many patients with cluster headache report use of illicit drugs. We
      systematically assessed the use of illicit drugs and their effects in a well
      defined Dutch cluster headache population. Methods In this cross-sectional
      explorative study, 756 people with cluster headache received a questionnaire on
      lifetime use and perceived effects of illicit drugs. Results were compared with
      age and sex-matched official data from the Dutch general population. Results
      Compared to the data from the general population, there were more illicit drug
      users in the cluster headache group (31.7% vs. 23.8%; p < 0.01). Reduction in
      attack frequency was reported by 56% (n = 22) of psilocybin mushroom, 60% (n = 3)
      of lysergic acid diethylamide and 50% (n = 2) of heroin users, and a decreased
      attack duration was reported by 46% (n = 18) of PSI, 50% (n = 2) of heroin and
      36% (n = 8) of amphetamine users. Conclusion In the Netherlands, people with
      cluster headache use illicit drugs more often than the general population. The
      question remains whether this is due to an actual alleviatory effect, placebo
      response, conviction, or common pathophysiological background between cluster
      headache and addictive behaviours such as drug use.

PMID- 30290702
TI  - The effectiveness of interventions targeting physical activity and/or sedentary
      behaviour in people with Multiple Sclerosis: a systematic review.
AB  - BACKGROUND: Remaining physically active is important to maintain functional
      ability and reduce the incidence of co-morbidities in people with Multiple
      Sclerosis. The aim of this review was to evaluate the effectiveness of
      interventions on physical activity or sedentary behaviour in people with Multiple
      Sclerosis. METHODS: A systematic search was conducted in May 2018 of the
      following databases: Web of Science Core Collections, Embase and Medline.
      Included studies were randomised controlled trials involving people with Multiple
      Sclerosis who completed an intervention, compared to any comparator. Outcomes
      included subjective or objective measures of physical activity or sedentary
      behaviour. Quality assessment was performed using the Physiotherapy Evidence
      Database scale. RESULTS: Twenty-five trials were included covering 1697
      participants, the majority of which had mild-moderate disability (average
      Physiotherapy Evidence Database score 6.2 +/- 1.5). Experimental interventions
      included exercise prescription (n = 5), behaviour change interventions (n = 10),
      combined exercise, and behaviour change techniques (n = 7) and education (n = 3).
      Generally, subjective but not objective physical activity improved in those with
      mild-moderate disability. Insufficient data existed on the effectiveness on
      sedentary behaviour. CONCLUSIONS: A discrepancy seems to exists between the
      effectiveness of physical activity interventions in people with Multiple
      Sclerosis depending on whether physical activity was assessed objectively or
      subjectively, with the latter indicating effects. Effects on sedentary behaviour
      remain to be elucidated. Implications for Rehabilitation Remaining physically
      active is important to maintain functional ability, independence, quality of
      life, and to reduce the incidence of co-morbidity. Exercise prescription,
      behaviour change interventions, combined exercise and behaviour change
      interventions, and health promotion education appear to subjectively improve
      physical activity in people with Multiple Sclerosis with mild-moderate
      disability, yet this is often not the case when measured objectively. There is a
      lack of evidence to support the effectiveness of these interventions on sedentary
      behaviour.

PMID- 30290703
TI  - Factors influencing middle managers' commitment to the implementation of
      innovations in cancer care.
AB  - Objective To identify and illuminate influences on middle managers' commitment to
      innovation implementation. Methods A qualitative study was conducted, employing
      the methods of grounded theory. Semi-structured interviews were used to collect
      data from middle managers (n = 15) in Nova Scotia and New Brunswick, Canada. Data
      were collected and analysed concurrently, using an inductive constant comparative
      approach. Data collection and analysis continued until theoretical saturation was
      reached. Results The data revealed middle managers contemplate two central issues
      in terms of their commitment to implementation, that is whether or not they fully
      engage in and support the implementation of a particular innovation. These issues
      are (1) ease of implementation and (2) potential benefit for patients. Middle
      managers' views and expectations related to ease of implementation are influenced
      by available resources, fit with setting, and stakeholder buy-in. Their views on
      patient benefit are influenced by external evidence of benefit and local gaps in
      care. Conclusions These findings provide further insight into the factors that
      influence middle managers' commitment to innovation implementation, and how
      middle managers consider these factors in the context of their work settings.

PMID- 30290704
TI  - "LectureKeepr as a novel approach to lecture pre-reading:" UK medical students'
      perspectives.

PMID- 30290705
TI  - The teaching of child development and disability - How well has our medical
      school equipped us?

PMID- 30290706
TI  - Another longin SNARE for autophagosome-lysosome fusion-how does Ykt6 work?
AB  - : Formation of the autolysosome involves SNARE-mediated autophagosome-lysosome
      fusion, which is mediated by a combination of the Qa SNARE STX17 (syntaxin 17),
      the Qbc SNARE SNAP29 and the R-SNAREs VAMP7/8. 2 very recent reports have now
      implicated another R-SNARE with a longin domain, YKT6, in this fusion process.
      Interestingly, these reports painted two different pictures of YKT6's
      involvement. Studies in HeLa cells indicated that YKT6, acting independently of
      STX17, could form a separate SNARE complex with SNAP29 and another Qa SNARE to
      mediate autophagosome-lysosome fusion. Conversely, work in Drosophila larvae fat
      cells showed that while Ykt6 could form a SNARE complex with Snap29 and
      Syx17/Stx17, it is readily outcompeted by lysosomal Vamp7 in this regard.
      Moreover, its activity in autophagosome-lysosome fusion is not impaired by
      mutation of the supposedly critical ionic zero-layer residue from R to Q. In this
      regard, YKT6 may therefore act in a noncanonical way to regulate fusion. Here, we
      ponder on the fresh mechanistic perspectives on the final membrane fusion step of
      macroautophagy/autophagy offered by these new findings. Further, we propose
      another possible mechanism as to how YKT6 might act, which may provide some
      reconciliation to the differences observed. ABBREVIATIONS: LD: longin domain.

PMID- 30290707
TI  - The cargo receptor SQSTM1 ameliorates neurofibrillary tangle pathology and
      spreading through selective targeting of pathological MAPT (microtubule
      associated protein tau).
AB  - Accumulating evidence suggests that misfolded MAPT (microtubule associated
      protein tau), the main component of neurofibrillary tangles in tauopathies, is
      subject to degradation by the autophagy-lysosomal pathway. Selective autophagy is
      a subtype of macroautophagy that requires cargo receptors, such as OPTN
      (optineurin) or SQSTM1, to recognize specific targets for their sequestration
      within the autophagosome and their eventual degradation by the lysosome, although
      their roles in targeting distinct MAPT species have not been fully investigated.
      Using cargo receptor knockout cell lines and a seeding-based cellular assay in
      which neurofibrillary tangle pathology can be modeled in vitro, we reveal that
      while OPTN primarily targets soluble MAPT expressed in physiological conditions,
      SQSTM1 predominantly degrades insoluble but not soluble mutant MAPT. Endogenous
      SQSTM1 colocalizes with misfolded and aggregated MAPT species in vitro and in
      vivo, and both this colocalization and its function in MAPT clearance require
      both the LC3-interacting region (LIR) motif and also the PB1 self-polymerization
      domain of SQSTM1. Further, pathogenic MAPT accumulation reduces basal
      macroautophagy/autophagy in vitro and is associated with a compensatory
      upregulation of the lysosomal pathway in vivo. Finally, increased expression of
      SQSTM1 in MAPT transgenic mouse brains ameliorates MAPT pathology and prion-like
      spreading. Our results uncover distinct properties of selective autophagy
      receptors in targeting different MAPT species, implicate compromised autophagy as
      a potential underlying factor in mutant MAPT deposition, and demonstrate a potent
      and specific role of SQSTM1 in targeted clearance of pathogenic MAPT, through
      which it blocks neurofibrillary tangle accumulation and pathological spreading.
      Abbreviations: AAV: adeno-associated virus; AD: Alzheimer disease; ALP: autophagy
      lysosomal pathway; ALS: amyotrophic lateral sclerosis; CALCOCO2/NDP52: calcium
      binding and coiled-coil domain 2; FTD: frontotemporal dementias; HD: Huntington
      disease; HTT: huntingtin; LIR: LC3-interacting region; NBR1: autophagy cargo
      receptor; NFE2L2/Nrf2: nuclear factor, erythroid derived 2, like 2; NFTs:
      neurofibrillary tangles; MAPT: microtubule associated protein tau; OPTN:
      optineurin; p-MAPT: hyperphosphorylated MAPT; PFA: paraformaldehyde; TARDBP/TDP
      43: TAR DNA binding protein; TAX1BP1 Tax1: binding protein 1; ThioS: thioflavin
      S; UBA: ubiquitin-associated.

PMID- 30290708
TI  - YKT6 as a second SNARE protein of mammalian autophagosomes.
AB  - Mammalian autophagosomes possess the Qa-SNARE STX17 (syntaxin 17) for fusion with
      lysosomes. However, STX17 is not absolutely required for fusion because STX17
      knockout cells partially retain autophagosome-lysosome fusion activity. We
      recently identified YKT6, an R-SNARE, as another autophagosomal SNARE protein
      that acts independently of STX17 in mammals. Here, we discuss the features and
      functions of autophagosomal SNARE proteins by comparing STX17 and YKT6.
      Abbreviations: SNARE, soluble N-ethylmaleimide-sensitive factor attachment
      protein receptor; STX17, syntaxin 17.

PMID- 30290709
TI  - Therapeutic response to glucocorticoids, anticoagulation and plasma exchange in a
      patient with primary antiphospholipid syndrome presenting with purpura fulminans.
AB  - We report the case of a 25-year-old female patient who presented with purpura
      fulminans as a manifestation of primary antiphospholipid syndrome. Purpura
      fulminans is considered a rare cutaneous manifestation of antiphospholipid
      syndrome. Most frequently, it occurs in the context of catastrophic
      antiphospholipid syndrome and is associated with significant morbidity and
      mortality, either due to loss of affected extremities or thromboembolic damage to
      internal organs. After insufficient efficacy of parenteral anticoagulation and
      oral glucocorticosteroid treatment, we escalated treatment to high-dose
      intravenous glucocorticosteroid and five consecutive sessions of plasma exchange
      with good and sustained clinical response. At follow-up six months after
      admission, skin manifestations had healed with scarring, and no additional
      thrombotic events had occurred. Plasma exchange may hold promise as a therapeutic
      option in refractory or severe cases of antiphospholipid syndrome-related purpura
      fulminans with extensive cutaneous necrosis, although evidence is limited.

PMID- 30290710
TI  - Endovascular retrograde approach may be a better option for acute tandem
      occlusions stroke.
AB  - Objective The endovascular treatment strategy for acute tandem occlusion stroke
      is challenging, and controversy exists regarding which lesion should be treated
      first. This study addresses the uncertainty regarding the priority choice for
      thrombectomy in acute anterior circulation tandem occlusion stroke. Methods We
      analysed the clinical and angiographic data of tandem stroke patients who
      underwent interventional therapy from the endovAsCular Treatment of acUte
      Anterior circuLation ischaemic stroke (ACTUAL) registry. Recanalisation was
      assessed according to the modified thrombolysis in cerebral infarction score.
      Clinical outcome was evaluated at 90 days using the modified Rankin scale score.
      Results Sixty tandem occlusion stroke patients were enrolled. Thirty-one (51.7%)
      patients received anterograde therapy, while 29 (48.3%) patients underwent the
      retrograde approach. Successful recanalisation (modified thrombolysis in cerebral
      infarction score 2b-3) occurred in 78.3% (47/60) of patients, and 50.0% (30/60)
      of patients achieved a modified Rankin scale score of 0-2 at 90 days. Patients
      undergoing the retrograde approach spent less time in distal occlusion
      recanalisation (125 (86-167) vs. 95 (74-122) minutes; P = 0.04) and achieved
      better functional outcomes at 90 days (69.0% (20/29) vs. 32.3% (10/31); P =
      0.004) than patients who received anterograde therapy. The retrograde approach
      was associated with favourable clinical outcomes (odds ratio 0.21; 95% confidence
      interval 0.07-0.64; P = 0.006). Conclusion For acute tandem occlusion stroke,
      favourable outcomes were better in patients undergoing retrograde therapy than in
      patients who received the anterograde approach. Future randomised trials are
      warranted to determine the optimal treatment.

PMID- 30290711
TI  - pH-dependent regulation of SQSTM1/p62 during autophagy.
AB  - During macroautophagy/autophagy, SQSTM1/p62 plays dual roles as a key mediator of
      cargo selection and as an autophagic substrate. SQSTM1 links N-degrons and/or
      ubiquitinated cargoes to the autophagosome by forming homo- or hetero-oligomers,
      although its N-degron recognition and oligomerization mechanisms are not well
      characterized. We recently found that SQSTM1 is a novel type of N-recognin whose
      ZZ domain provides a negatively-charged binding pocket for Arg-charged N-degron
      (Nt-Arg), a prototype type-1 substrate. Although differences in binding affinity
      exist for each N-degron, SQSTM1 also interacts with type-2 N-degrons, such as Nt
      Tyr and Nt-Trp. Intriguingly, interactions between SQSTM1's ZZ domain and various
      N-degrons are greatly influenced by pH-dependent SQSTM1 oligomerization via its
      PB1 domain. Because cellular pH conditions vary from neutral to acidic depending
      on the stage of autophagy, the pH-dependent regulation of SQSTM1's
      oligomerization must be tightly coupled with the autophagic process.

PMID- 30290713
TI  - Exploring lateralization during memory through hemispheric pre-activation:
      Differences based on the stimulus type.
AB  - The original approach of the Hemispheric Encoding/Retrieval Asymmetry model
      (HERA) was aimed at the operations of encoding and retrieving episodic memories.
      However, whether HERA presumptions can apply to different types of stimuli (e.g.,
      words and pictures) continues to be a matter of debate. Therefore, in order to
      analyse the effects of brain pre-activation on subsequent memory, HERA was tested
      through a hand-clenching paradigm using four types of stimuli: words, fractal
      images, silhouettes of common objects, and pseudowords. Results revealed that
      only the memory of words and pseudowords was enhanced by hand-clenching pre
      activation, according to HERA predictions. Since the cognitive processes
      underlying recognition of verbal stimuli are considered to follow a cognitive
      route involving grapheme-morpheme conversion, it could be hypothesized that hand
      clenching pre-activation might be associated with a selective pre-activation of
      the brain circuits participating in that pathway. Hence, the present work
      broadens possible interpretations behind the effects of hand-clenching on memory,
      based on the process engaged and the type of stimulus to be remembered.

PMID- 30290715
TI  - Procalcitonin as an early indicator of urosepsis following prostate biopsy.
AB  - BACKGROUND: To investigate the usefulness of serum procalcitonin (PCT) in the
      early diagnosis of urinary tract infection (UTI) and urosepsis following
      transrectal prostate biopsy. METHODS: In this prospective observational study,
      227 patients who underwent transrectal ultrasound-guided prostate biopsy were
      evaluated. The relationship between urosepsis and age, serum PCT, C-reactive
      protein, prostate-specific antigen (PSA), prostate volume, PSA density and
      pathologic results following biopsy was assessed. Serum PCT level was measured in
      all patients immediately before the biopsy and at the post-biopsy day 2. RESULTS:
      Of the 227 patients, 11 (4.8%) developed UTI with positive urine culture without
      urosepsis and 5 (2.2%) developed urosepsis within 30 days after biopsy. The
      concentration of PCT was within the normal range before the biopsy. Procalcitonin
      concentration at post-biopsy day 2 was significantly higher in patients who
      developed urosepsis (1.91 +/- 2.99 ng/ml vs. 0.05 +/- 0.08 ng/ml; p = .004)
      compared with non-UTI patients. Only elevated PCT level at post-biopsy day 2 was
      a statistically significant independent predictor of post-biopsy urosepsis. The
      area under the ROC curve for the prediction of urosepsis was 0.976 (95%CI: 0.941
      1.000) and a cut-off 0.095 ng/ml in the level of PCT at post-biopsy day 2 yielded
      a sensitivity of 100% and specificity of 93.8% in detecting urosepsis following
      biopsy. CONCLUSIONS: Procalcitonin appears to be a useful early biomarker to
      predict the urosepsis following prostate biopsy. Patients with elevated PCT value
      should be closely monitored after the biopsy.

PMID- 30290714
TI  - PRKN-regulated mitophagy and cellular senescence during COPD pathogenesis.
AB  - : Cigarette smoke (CS)-induced accumulation of mitochondrial damage has been
      widely implicated in chronic obstructive pulmonary disease (COPD) pathogenesis.
      Mitophagy plays a crucial role in eliminating damaged mitochondria, and is
      governed by the PINK1 (PTEN induced putative protein kinase 1)-PRKN (parkin RBR
      E3 ubiquitin protein ligase) pathway. Although both increased PINK1 and reduced
      PRKN have been implicated in COPD pathogenesis in association with mitophagy,
      there are conflicting reports for the role of mitophagy in COPD progression. To
      clarify the involvement of PRKN-regulated mitophagy in COPD pathogenesis, prkn
      knockout (KO) mouse models were used. To illuminate how PINK1 and PRKN regulate
      mitophagy in relation to CS-induced mitochondrial damage and cellular senescence,
      overexpression and knockdown experiments were performed in airway epithelial
      cells (AEC). In comparison to wild-type mice, prkn KO mice demonstrated enhanced
      airway wall thickening with emphysematous changes following CS exposure. AEC in
      CS-exposed prkn KO mice showed accumulation of damaged mitochondria and increased
      oxidative modifications accompanied by accelerated cellular senescence. In vitro
      experiments showed PRKN overexpression was sufficient to induce mitophagy during
      CSE exposure even in the setting of reduced PINK1 protein levels, resulting in
      attenuation of mitochondrial ROS production and cellular senescence. Conversely
      PINK1 overexpression failed to recover impaired mitophagy caused by PRKN
      knockdown, indicating that PRKN protein levels can be the rate-limiting factor in
      PINK1-PRKN-mediated mitophagy during CSE exposure. These results suggest that
      PRKN levels may play a pivotal role in COPD pathogenesis by regulating mitophagy,
      suggesting that PRKN induction could mitigate the progression of COPD.
      ABBREVIATIONS: AD: Alzheimer disease; AEC: airway epithelial cells; BALF:
      bronchoalveolar lavage fluid; AKT: AKT serine/threonine kinase; CALCOCO2/NDP52:
      calcium binding and coiled-coil domain 2; CDKN1A: cyclin dependent kinase
      inhibitor 1A; CDKN2A: cyclin dependent kinase inhibitor 2A; COPD: chronic
      obstructive pulmonary disease; CS: cigarette smoke; CSE: CS extract; CXCL1: C-X-C
      motif chemokine ligand 1; CXCL8: C-X-C motif chemokine ligand 8; HBEC: human
      bronchial epithelial cells; 4-HNE: 4-hydroxynonenal; IL: interleukin; KO:
      knockout; LF: lung fibroblasts; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule
      associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase;
      8-OHdG: 8-hydroxy-2'-deoxyguanosine; OPTN: optineurin; PRKN: parkin RBR E3
      ubiquitin protein ligase; PCD: programmed cell death; PFD: pirfenidone; PIK3C:
      phosphatidylinositol-4:5-bisphosphate 3-kinase catalytic subunit; PINK1: PTEN
      induced putative kinase 1; PTEN: phosphatase and tensin homolog; RA: rheumatoid
      arthritis; ROS: reactive oxygen species; SA-GLB1/beta-Gal: senescence-associated
      galactosidase, beta 1; SASP: senescence-associated secretory phenotype; SNP:
      single nucleotide polymorphism; TNF: tumor necrosis factor.

PMID- 30290712
TI  - Epigenetically distinct sister chromatids and asymmetric generation of tumor
      initiating cells.
AB  - Cancer stem cells (CSC) are thought to be an important source of cancer cells in
      tumors of different origins. Mounting evidence suggests they are generated
      reversibly from existing cancer cells, and supply new cancer cells during tumor
      progression and following therapy. Elegant lineage mapping stud(ies are
      identifying progenitors, and in some cases differentiated cells, as targets of
      transformation in a variety of tumors. Recent evidence suggests resulting tumor
      initiating cells (TIC) might be distinct from CSC. Molecular pathways leading
      from cells of tumor origin to precancerous lesions and cancer cells are only
      beginning to be unraveled. We review a pathway where asymmetric division of
      precancerous cells generates TIC in a K-Ras-initiated model of lung cancer. And,
      we compare unexpected steps in this asymmetric division to those evident in well
      studied stem cell models.

PMID- 30290716
TI  - Resolution of large aortic valve vegetations in antiphospholipid syndrome treated
      with therapeutic anticoagulation: a report of two cases and literature review.
AB  - Non-bacterial thrombotic endocarditis in antiphospholipid syndrome presents a
      management dilemma. Large mobile valvular lesions pose an increased risk of
      stroke and arterial embolization. However, surgical excision or valve replacement
      in such patients carries high morbidity and mortality, while anticoagulation
      alone has limited data. We describe two patients with antiphospholipid syndrome
      presenting with neurologic events and large non-bacterial aortic valve
      vegetations. Both patients were successfully managed with anticoagulation and
      demonstrated rapid dissolution of lesions without evidence of recurrent embolic
      events. We provide a literature review describing additional cases managed with
      anticoagulation with dissolution of valvular lesions over time. Our cases further
      support the efficacy and safety of anticoagulation in patients with
      antiphospholipid syndrome and non-bacterial thrombotic endocarditis in the
      context of arterial embolization.

PMID- 30290717
TI  - Therapeutic potential of allogeneic mesenchymal stromal cells transplantation for
      lupus nephritis.
AB  - Animal and human studies have suggested the potential of mesenchymal stromal
      cells (MSCs) to treat systemic lupus erythematosus (SLE). Here, we present the
      results of compassionate MSC treatments for three SLE patients to provide the
      proof of concept for a randomized and controlled clinical trial. Three patients
      of different ethnicities who suffer from chronic SLE, and who presented with
      class IV active proliferative nephritis confirmed by biopsy, were treated with
      allogeneic MSCs from healthy donors. Ninety million cells were infused
      intravenously into each patient during high and very high activity disease flare
      ups and follow-up was continued for 9 months. Multi-organic affectation was
      quantified by the SLE disease activity index (SLEDAI), and indicators of lupus
      nephritis activity, such as proteinuria, as well as lymphocyte and monocyte
      antigens and anti-HLA antibodies were measured at 1, 3, 6, and 9 months after
      treatment. Proteinuria levels improved dramatically during the 1st month after
      treatment and the ameliorations were sustained throughout the follow-up period.
      SLEDAI scores revealed early, durable, and substantial remissions that were
      complete for two patients and partial for the third patient and that permitted
      medication doses to be reduced 50-90%. These favourable outcomes support
      completion of the randomized and controlled MSC trial for SLE.

PMID- 30290718
TI  - RAB30 regulates PI4KB (phosphatidylinositol 4-kinase beta)-dependent autophagy
      against group A Streptococcus.
AB  - Macroautophagy/autophagy plays an important role in the immune response to
      invasion by intracellular pathogens such as group A Streptococcus (GAS;
      Streptococcus pyogenes). We previously identified RAB30, a Golgi-resident GTPase,
      as a novel anti-bacterial autophagic regulator in the formation of GAS-containing
      autophagosome-like vacuoles (GcAVs); however, the precise mechanism underlying
      this process remains elusive. Here, we elucidate a novel property of RAB30: the
      ability to recruit PI4KB (phosphatidylinositol 4-kinase beta) to the Golgi
      apparatus and GcAVs. We found that trans-Golgi network (TGN) vesicles were
      incorporated into GcAVs via RAB30 to promote GcAV formation. Moreover, depletion
      of phosphatidylinositol-4-phosphate (PtdIns4P), a phosphatidylinositol enriched
      in the TGN, by wortmannin and phenylarsine oxide, followed by subsequent
      repletion with exogenous PtdIns4P revealed that PtdIns4P is crucial for GcAV
      formation. Furthermore, we identify an interaction between RAB30 and PI4KB, in
      which the knockdown of RAB30 decreased the localization of PI4KB to the TGN and
      GcAVs. Finally, PI4KB knockout suppressed autophagy by inhibiting GcAV formation,
      resulting in the increased survival of GAS. Our results demonstrate a novel
      autophagosomal formation mechanism involving coordinative functions of RAB30 and
      PI4KB distinct from those utilized in canonical autophagy. Abbreviations: GAS:
      group A Streptococcus; GcAVs: GAS-containing autophagosome-like vacuoles; PI4KB:
      phosphatidylinositol 4-kinase beta; PtdIns: phosphatidylinositol; PtdIns3P:
      phosphatidylinositol-3-phosphate; PtdIns4P: phosphatidylinositol-4-phosphate;
      PtdIns5P: phosphatidylinositol-5-phosphate; SLO: streptolysin O; TGN: trans-Golgi
      network; TGOLN2: trans-golgi network protein 2; PH: plekstrin homology; OSBP:
      oxysterol binding protein.

PMID- 30290719
TI  - MITF-MIR211 axis is a novel autophagy amplifier system during cellular stress.
AB  - Macroautophagy (autophagy) is an evolutionarily conserved recycling and stress
      response mechanism. Active at basal levels in eukaryotes, autophagy is
      upregulated under stress providing cells with building blocks such as amino
      acids. A lysosome-integrated sensor system composed of RRAG GTPases and MTOR
      complex 1 (MTORC1) regulates lysosome biogenesis and autophagy in response to
      amino acid availability. Stress-mediated inhibition of MTORC1 results in the
      dephosphorylation and nuclear translocation of the TFE/MITF family of
      transcriptional factors, and triggers an autophagy- and lysosomal-related gene
      transcription program. The role of family members TFEB and TFE3 have been studied
      in detail, but the importance of MITF proteins in autophagy regulation is not
      clear so far. Here we introduce for the first time a specific role for MITF in
      autophagy control that involves upregulation of MIR211. We show that, under
      stress conditions including starvation and MTOR inhibition, a MITF-MIR211 axis
      constitutes a novel feed-forward loop that controls autophagic activity in cells.
      Direct targeting of the MTORC2 component RICTOR by MIR211 led to the inhibition
      of the MTORC1 pathway, further stimulating MITF translocation to the nucleus and
      completing an autophagy amplification loop. In line with a ubiquitous function,
      MITF and MIR211 were co-expressed in all tested cell lines and human tissues, and
      the effects on autophagy were observed in a cell-type independent manner. Thus,
      our study provides direct evidence that MITF has rate-limiting and specific
      functions in autophagy regulation. Collectively, the MITF-MIR211 axis constitutes
      a novel and universal autophagy amplification system that sustains autophagic
      activity under stress conditions. Abbreviations: ACTB: actin beta; AKT: AKT
      serine/threonine kinase; AKT1S1/PRAS40: AKT1 substrate 1; AMPK: AMP-activated
      protein kinase; ATG: autophagy-related; BECN1: beclin 1; DEPTOR: DEP domain
      containing MTOR interacting protein; GABARAP: GABA type A receptor-associated
      protein; HIF1A: hypoxia inducible factor 1 subunit alpha; LAMP1: lysosomal
      associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1
      light chain 3 beta; MAPKAP1/SIN1: mitogen-activated protein kinase associated
      protein 1; MITF: melanogenesis associated transcription factor; MLST8: MTOR
      associated protein, LST8 homolog; MRE: miRNA response element; MTOR: mechanistic
      target of rapamycin kinase; MTORC1: MTOR complex 1; MTORC2: MTOR complex 2;
      PRR5/Protor 1: proline rich 5; PRR5L/Protor 2: proline rich 5 like; RACK1:
      receptor for activated C kinase 1; RPTOR: regulatory associated protein of MTOR
      complex 1; RICTOR: RPTOR independent companion of MTOR complex 2; RPS6KB/p70S6K:
      ribosomal protein S6 kinase; RT-qPCR: quantitative reverse transcription
      polymerase chain reaction; SQSTM1: sequestosome 1; STK11/LKB1: serine/threonine
      kinase 11; TFE3: transcription factor binding to IGHM enhancer 3; TFEB:
      transcription factor EB; TSC1/2: TSC complex subunit 1/2; ULK1: unc-51 like
      autophagy activating kinase 1; UVRAG: UV radiation resistance associated; VIM:
      vimentin; VPS11: VPS11, CORVET/HOPS core subunit; VPS18: VPS18, CORVET/HOPS core
      subunit; WIPI1: WD repeat domain, phosphoinositide interacting 1.

PMID- 30290720
TI  - A direct aspiration first pass technique with the new ARC catheter for
      thrombectomy of large vessel occlusion strokes: A multicenter study.
AB  - Background and purpose A direct aspiration first pass technique involves first
      line aspiration to remove the thrombus through a large-bore aspiration catheter
      in large vessel strokes. The aim of this study was to assess safety and clinical
      outcomes with a direct aspiration first pass technique using the new ARC
      catheter. Methods A retrospective analysis of prospectively collected data from
      three university hospitals was performed between June 2016 and May 2018. The
      following parameters of all acute ischemic stroke interventions using the ARC
      catheter were analyzed: use of intravenous thrombolysis, National Institutes of
      Health Stroke Scale scores at presentation and discharge, successful reperfusion
      (modified Thrombolysis in Cerebral Infarction 2b-3), procedure duration,
      procedure-related complications and 90-day clinical outcome (modified Rankin
      Scale score). Results In total, 41 patients were included in the study and
      anterior circulation occlusion was noted in 35 (85%). The median National
      Institutes of Health Stroke Scale at admission was 18 and prior intravenous
      thrombolysis was administered in 35 patients (85%). Only six (15%) patients
      required the use of a rescue stent retriever. Successful reperfusion was achieved
      in 40 patients (98%) with a median procedure time of 32 minutes. No catheter
      related complications were observed. Symptomatic intracerebral hemorrhage
      occurred in one patient (2%). Median National Institutes of Health Stroke Scale
      at discharge was 3; 49% were independent and 10% died at 90 days. Conclusions In
      the present study, the ARC catheter allowed a 98% successful reperfusion rate.
      The complication rate was in line with those of previous a direct aspiration
      first pass technique publications.

PMID- 30290721
TI  - RNase Y-mediated regulation of the streptococcal pyrogenic exotoxin B.
AB  - Endoribonuclease Y (RNase Y) is a crucial regulator of virulence in Gram-positive
      bacteria. In the human pathogen Streptococcus pyogenes, RNase Y is required for
      the expression of the major secreted virulence factor streptococcal pyrogenic
      exotoxin B (SpeB), but the mechanism involved in this regulation remains elusive.
      Here, we demonstrate that the 5' untranslated region of speB mRNA is processed by
      several RNases including RNase Y. In particular, we identify two RNase Y cleavage
      sites located downstream of a guanosine (G) residue. To assess whether this
      nucleotide is required for RNase Y activity in vivo, we mutated it and
      demonstrate that the presence of this G residue is essential for the processing
      of the speB mRNA 5' UTR by RNase Y. Although RNase Y directly targets and
      processes speB, we show that RNase Y-mediated regulation of speB expression
      occurs primarily at the transcriptional level and independently of the processing
      in the speB mRNA 5' UTR. To conclude, we demonstrate for the first time that
      RNase Y processing of an mRNA target requires the presence of a G. We also
      provide new insights on the speB 5' UTR and on the role of RNase Y in speB
      regulation.

PMID- 30290722
TI  - Fatal gastric distension in a gold thioglucose mouse model of obesity.
AB  - This case report addresses the problem of underreporting negative results and
      adverse side effects in animal testing. We present our findings regarding a
      hyperphagic mouse model associated with unforeseen high mortality. The results
      outline the necessity of reporting detailed information in the literature to
      avoid duplication. Obese mouse models are essential in the study of obesity,
      metabolic syndrome and diabetes mellitus. An experimental model of obesity can be
      induced by the administration of gold thioglucose (GTG). After transcending the
      blood-brain barrier, the GTG molecule interacts with regions of the ventromedial
      hypothalamus, thereby primarily targeting glucose-sensitive neurons. When these
      neurons are impaired, mice become insensitive to the satiety effects of glucose
      and develop hyperphagia. In a pilot study for optimising dosage and body weight
      development, C57BL/6 mice were treated with GTG (0.5 mg/g body weight) or saline,
      respectively. Animals were provided a physiological amount of standard diet (5 g
      per animal) for the first 24 hours after treatment to prevent gastric dilatation.
      Within 24 hours after GTG injection, all GTG-treated animals died of gastric
      overload and subsequent circulatory shock. Animals developed severe attacks of
      hyperphagia, and as the amount of provided chow was restricted, mice exhibited
      unforeseen pica and ingested bedding material. These observations strongly
      suggest that restricted feeding is contraindicated concerning GTG application.
      Presumably, the impulse of excessive food intake was a strong driving force.
      Therefore, the actual degree of suffering in the GTG-induced model of hyperphagia
      should be revised from moderate to severe.

PMID- 30290723
TI  - Improved care and support for people in mental health crisis.
AB  - District nurses are increasingly required to manage the physical health needs of
      patients who misuse substances or have mental health problems. Some patients have
      a mental health crisis in the community and come to the attention of the police.
      Concern over the use of police powers to detain people in a mental health crisis
      and in particular the use police cells as a place of safety has led to changes in
      the law. In this article the author updates district nurses on the amendments to
      police powers under the Mental Health Act 1983 introduced by the Policing and
      Crime Act 2017, part 4 chapter 4 designed to better manage those people
      experiencing a mental health crisis.

PMID- 30290724
TI  - Too old to stop smoking?

PMID- 30290725
TI  - Diabetes care in care home and residential settings.
AB  - An increasing number of people require insulin to manage their diabetes, many of
      them in supported environments such as residential care homes. Community nursing
      teams are likely to have a growing caseload of care home residents who require
      diabetes care, including insulin injections, and many unregistered practitioners
      are being asked to take on this role. If community nurse leads, matrons, frailty
      teams and pharmacy teams work together to provide training to staff in care homes
      (particularly unregistered practitioners), diabetes care can be improved. This
      has to be suitable for groups and for people with different levels of
      understanding, and supported by written resources. Courses are interactive to
      engage and motivate all learners, and methods of teaching include group work,
      visual teaching aids and games. Self-assessment around competencies, using a
      competency framework, not only demonstrates the development of staff but also
      highlights key areas of diabetes care.

PMID- 30290726
TI  - Helping people to get about.

PMID- 30290727
TI  - No tears for skin tears.

PMID- 30290728
TI  - Technology integrated health management for dementia.
AB  - Pioneering advances have been made in Internet of Things technologies (IoT) in
      healthcare. This article describes the development and testing of a bespoke IoT
      system for dementia care. Technology integrated health management (TIHM) for
      dementia is part of the NHS England National Test Bed Programme and has involved
      trailing the deployment of network enabled devices combined with artificial
      intelligence to improve outcomes for people with dementia and their carers. TIHM
      uses machine learning and complex algorithms to detect and predict early signs of
      ill health. The premise is if changes in a person's health or routine can be
      identified early on, support can be targeted at the point of need to prevent the
      development of more serious complications.

PMID- 30290730
TI  - Treating patients with long-term conditions in the 21st century.

PMID- 30290729
TI  - Supporting student nurses who have their first clinical placement in the
      community nursing team.
AB  - First year student nurses are increasingly undertaking their first placement with
      community nurses. The importance of how this initial learning experience is
      introduced by the higher education institution, as well as how the student is
      welcomed and integrated into the community nursing team, cannot be
      underestimated. Following positive anonymous feedback from students, which
      indicated that they had benefitted from the introduction, welcome and integration
      they experienced, the university and mentors reviewed how this had been done to
      identify good practice to share with colleagues. Students indicated that their
      welcome and integration had helped them to feel part of the team and enhanced
      learning, because they were so well supported, and mentors had facilitated
      learning experiences by acknowledging that this was their first placement
      experience. It is notable that mentors were committed to the students' learning
      and used workplace social capital to optimise the student experience. At a time
      when retention of students is essential to increase the future workforce, mentors
      dedicated to student learning are acting as ambassadors for the community
      workforce, and may well encourage students to have a career in community nursing.

PMID- 30290731
TI  - Fatigue in palliative care.

PMID- 30290732
TI  - Frailty in older people: a principle-based concept analysis.
AB  - Frailty is a term that presents many difficulties for policy makers and
      clinicians due to the lack of consensus in defining frailty in a way that meets
      the needs of older people. A principle-based concept analysis was used to examine
      the scientific literature across four perspectives: medicine, nursing, social
      sciences, and occupational and physiotherapy. The purpose was to identify the
      conceptual components of frailty as revealed by analysis of the literature, and
      to develop a theoretical definition of frailty. The findings exposed
      commonalities in implied meanings both within and across perspectives. The
      strengths of frailty as a concept are revealed in the implications for clinical
      practice and relevance to health professionals. The limitations reflect a concept
      that is still evolving and further research is recommended but this should not
      stop health professionals engaging in this process. The definition developed in
      this study will enhance existing knowledge and promote a shared understanding to
      unite different disciplines in recognising frailty as an important concept.

PMID- 30290733
TI  - Left calf haematoma mimicking deep vein thrombosis.

PMID- 30290734
TI  - An unusual cause of chronic back pain: retroperitoneal ganglioneuroma.

PMID- 30290735
TI  - Cardiopulmonary exercise testing: valuable stratification tool or waste of time?

PMID- 30290736
TI  - Risks associated with the use of fluoroquinolones.
AB  - Fluoroquinolones are a widely used class of antibiotic that are effective in
      treating a wide variety of pathogens. Despite their popularity there is
      increasing concern regarding the potential complications associated with these
      agents. Patients who take a fluoroquinolone have an increased risk of developing
      tendinopathy, peripheral neuropathy, and aortic aneurysm or dissection. Providers
      should consider the risk of these potential complications before using these
      medications.

PMID- 30290737
TI  - Assessing volume status and fluid responsiveness in critical care.

PMID- 30290738
TI  - A straight to first diagnostic procedure pathway for suspected colorectal cancer.

PMID- 30290740
TI  - Typhus and the spotted fevers.

PMID- 30290739
TI  - Fungal prostatic abscess erupting through the penis.

PMID- 30290741
TI  - Acute medical problems in pregnancy.
AB  - The maternal population in the UK has become an increasingly challenging group of
      patients to manage. Women with pre-existing and often complex medical conditions
      are successfully conceiving. Most physicians will have had some involvement in
      the care of obstetric patients admitted with medical problems, and a lack of
      experience and fear of causing harm may result in essential investigations and
      treatment being withheld. The physiological changes in pregnancy can complicate
      the interpretation of observations and test results. This article discusses the
      presentation of commonly encountered medical problems in the obstetric
      population, including breathlessness, chest pain, palpitations, seizure and
      headache. It covers specific investigations and suggested treatment in this
      subset of patients. These women should receive the same level of care and
      attention as those who are not pregnant. Early diagnosis and effective management
      can help to reduce maternal morbidity and mortality caused by medical problems
      arising during pregnancy.

PMID- 30290742
TI  - The cutting edge of surgery 50 years ago.

PMID- 30290743
TI  - The clinical approach to managing herpes simplex virus encephalitis.
AB  - This article explains the approach to managing a patient with herpes simplex
      virus encephalitis. Acute encephalopathy is a common and often intimidating
      presentation in an acute general medical setting. Application of key principles
      will enable the generalist to take life-saving action before obtaining any
      specialist input. Viral infection is the most common cause (48.2%) of
      encephalitis; another large group is cases of autoimmune aetiology. Early
      diagnosis of encephalitis is crucial to ensure that the right treatment is given
      on time. Guidelines on the management of viral encephalitis were published by the
      British Association of Neurologists and British Infection Association ( Solomon
      et al, 2012 ), but adherence to these standards by clinicians has been found to
      be suboptimal ( Han and Coebergh, 2017 ). This puts lives in danger, in the
      context of a treatable, serious, acute presentation. Although viral infection is
      the most common cause of encephalitis, an awareness of rarer forms of autoimmune
      encephalitis is necessary. The differential diagnosis of autoimmune encephalitis
      is important because the disease is potentially treatable with immunosuppressive
      agents. Paraneoplastic limbic encephalitis may present months or years before the
      detection of a tumour.

PMID- 30290745
TI  - Use of antiretroviral drugs to prevent the transmission and acquisition of HIV.

PMID- 30290744
TI  - Understanding and interpreting funnel plots for the clinician.
AB  - Funnel plots are an increasingly common graphical tool which are widely used in
      the literature. They were first introduced by Light and Pillemer in 1984 . In
      scientific literature, funnel plots are used to identify the probability of bias
      in meta-analyses and compare institutional performance. The ability to identify
      variation is better with graphical than tabular display. In addition, the way
      data are presented can directly influence the interpretation of results. This was
      demonstrated by Marshall et al (2004) , who presented institutional mortality
      data in both a league table and control chart format. This study illustrated that
      when displayed as a league table, a greater number of units were identified for
      investigation than were actually required. The use of control charts or funnel
      plots may therefore show benefit in reducing the number of inappropriately
      labelled outliers. This article explains how clinicians should read and interpret
      funnel plots, and discusses their considerations and limitations.

PMID- 30290746
TI  - Seronegative granulomatosis with polyangiitis in multiple organ dysfunction.

PMID- 30290747
TI  - Learning opportunities in simulation for trainees.

PMID- 30290748
TI  - Idiopathic aortitis presenting as pyrexia of unknown origin and delirium.

PMID- 30290749
TI  - Improving the quality of medical handover on a paediatric ward.
AB  - Improving communication between health-care professionals is essential for
      patient safety. This article outlines a quality improvement project carried out
      to improve the quality of medical handover on a paediatric ward. The project
      incorporated the use of the SBAR (situation, background, assessment,
      recommendation) tool and use of a job book to highlight outstanding jobs in the
      daily handover. The project showed an improvement in the quality of handover and
      highlighted that a standardized approach to medical handover helped to ensure
      continuity of care of paediatric patients.

PMID- 30290750
TI  - Amniotic fluid embolism: a diagnosis of exclusion in cases of maternal collapse.

PMID- 30290752
TI  - Clinical News.

PMID- 30290751
TI  - Assessment of fever in the returning traveller.
AB  - Evaluation of people returning from trips abroad with fever is an important skill
      for all general physicians given the increasing trend in foreign travel. This
      evaluation should comprise a detailed travel history, thorough clinical
      examination, appropriate initial tests and a knowledge of when to ask for further
      advice. An understanding of the incubation periods of common imported infections
      and a syndromic approach to patients' symptoms is helpful in order to narrow down
      the likely diagnosis. The need to implement relevant infection control
      precautions has been highlighted by the recent Middle East respiratory syndrome
      coronavirus and Ebola virus disease outbreaks.

PMID- 30290753
TI  - Trauma radiology in the UK: an overview.
AB  - NHS Choices defines 'major trauma' as multiple, serious injuries that could
      result in disability or death. Worldwide, trauma is the leading cause of death
      and disability in people under 40 years of age. The National Audit Office
      estimates that there are at least 20 000 major trauma cases in England every
      year, resulting in 5400 deaths and leaving many others with serious permanent
      disability. Because the incidence of trauma is particularly high in younger
      patients, an average of 36 life years is lost for every trauma death ( Chaira and
      Cimbanassi, 2003 ). The landscape in major trauma imaging has evolved over the
      last 30 years, and this review chronicles these changes and the reasons for them,
      and looks at how the current guidelines have been formulated.

PMID- 30290754
TI  - The limping child: a systematic approach to assessment and management.

PMID- 30290755
TI  - Care closer to home: an evidence-based approach for straitened times.

PMID- 30290756
TI  - Prevalence of sarcopenia and its components in community-dwelling outpatient
      older adults and their relation with functionality.
AB  - AIM: Sarcopenia is recognized with its adverse functional outcomes. We aimed to
      report the prevalence of European Working Group on Sarcopenia in Older People
      (EWGSOP) defined sarcopenia and its individual components in community dwelling
      outpatient older adults and study the correlations of EWGSOP defined sarcopenia,
      muscle mass, muscle strength, and physical performance with functional status.
      MATERIAL AND METHODS: The subjects were prospectively recruited from the
      geriatrics outpatient clinics of our university hospital. Body composition was
      assessed with bioimpedance analysis. Muscle strength was assessed by measurement
      of hand grip strength with hydraulic hand dynamometer, physical performance was
      assessed by 4 meter usual gait speed (UGS). Impaired muscle function was defined
      as presence of low muscle strength and or slow gait speed. As a measure of
      functionality, modified version of Katz activities of daily living (ADL) and
      Lawton instrumental activities of daily living (IADL) were assessed. RESULTS: A
      total of 242 community dwelling outpatients with mean age of 79.4 +/- 5.7 years
      were enrolled. 31.8% were male. Prevalence of low muscle mass was 2.1% and
      impaired muscle function was 71.1%. Prevalence of EWGSOP defined sarcopenia was
      0.8% (1.3% in men and 0.6% in women). Most correlated parameter with ADL and IADL
      was the usual gait speed (r = 0.49, r = 0.63; p < .001, respectively). Grip
      strength was also correlated with ADL and IADL (r = 0.28, r = 0.35; p < .001).
      However, the skeletal muscle mass index (SMMI) was not correlated with ADL, IADL
      (p = .22, p = .22, respectively). In regression analysis, both ADL score and IADL
      scores were most related to UGS (beta = 0.5 and 0.6, p < .001), age (beta = -0.25
      and -0.2, p < .001) and then sarcopenia (beta = 0.1 and 0.1, p < .05) but was not
      related to hand grip strength or SMMI. CONCLUSIONS: The prevalence of sarcopenia
      was low as 0.8% albeit the presence of impaired muscle function in more than 2/3
      of the cases. We have found that EWGSOP defined sarcopenia had association with
      ADL and IADL. The gait speed component of sarcopenia had the strongest
      associations with functional measures but SMMI component did not have any
      relation. We suggest that although low muscle mass may be a parameter related to
      worse functionality, it should not be regarded prerequisite for presence of
      sarcopenia analogous to low bone mineral density for osteoporosis.

PMID- 30290757
TI  - Gene expression profiling of postnatal lung development in the marsupial gray
      short-tailed opossum (Monodelphis domestica) highlights conserved developmental
      pathways and specific characteristics during lung organogenesis.
AB  - BACKGROUND: After a short gestation, marsupials give birth to immature neonates
      with lungs that are not fully developed and in early life the neonate partially
      relies on gas exchange through the skin. Therefore, significant lung development
      occurs after birth in marsupials in contrast to eutherian mammals such as humans
      and mice where lung development occurs predominantly in the embryo. To explore
      the mechanisms of marsupial lung development in comparison to eutherians,
      morphological and gene expression analysis were conducted in the gray short
      tailed opossum (Monodelphis domestica). RESULTS: Postnatal lung development of
      Monodelphis involves three key stages of development: (i) transition from late
      canalicular to early saccular stages, (ii) saccular and (iii) alveolar stages,
      similar to developmental stages overlapping the embryonic and perinatal period in
      eutherians. Differentially expressed genes were identified and correlated with
      developmental stages. Functional categories included growth factors,
      extracellular matrix protein (ECMs), transcriptional factors and signalling
      pathways related to branching morphogenesis, alveologenesis and vascularisation.
      Comparison with published data on mice highlighted the conserved importance of
      extracellular matrix remodelling and signalling pathways such as Wnt, Notch, IGF,
      TGFbeta, retinoic acid and angiopoietin. The comparison also revealed changes in
      the mammalian gene expression program associated with the initiation of
      alveologenesis and birth, pointing to subtle differences between the non
      functional embryonic lung of the eutherian mouse and the partially functional
      developing lung of the marsupial Monodelphis neonates. The data also highlighted
      a subset of contractile proteins specifically expressed in Monodelphis during and
      after alveologenesis. CONCLUSION: The results provide insights into marsupial
      lung development and support the potential of the marsupial model of postnatal
      development towards better understanding of the evolution of the mammalian
      bronchioalveolar lung.

PMID- 30290759
TI  - Intra and interrater reliability and clinical feasibility of a simple measure of
      cervical movement sense in patients with neck pain.
AB  - BACKGROUND: Pattern tracing tasks can be used to assess cervical spine movement
      sense (CMS). A simple clinical measure of CMS (tracing fixed figure-of-eight (F8)
      and zigzag (ZZ) patterns with a head mounted laser) has been proposed and
      assessed in asymptomatic subjects. It is important to determine if examiner
      ratings of the traces are reliable and feasible for clinical use in those with
      neck pain. We therefore examined the intra- and inter-rater reliability of rating
      video recordings of the CMS tasks, and the feasibility of undertaking the tests
      in clinic by comparing slow motion versus real-time video ratings. METHODS: Cross
      sectional study examining neck pain subjects from a physiotherapy clinic. F8 and
      ZZ patterns traced with a head-mounted laser pointer at two velocities (accurate;
      accurate & fast) were videoed and later examined. Time (total time taken to
      complete the pattern), error frequency (number of deviations) and error magnitude
      (sum of deviations multiplied by distance from the central line) were measured.
      Two assessors independently evaluated the laser tracing videos in slow motion; a
      third rated the videos in real time. Intraclass correlation coefficients (ICC)
      and standard error of measurements (SEM) were calculated for intra- and inter
      tester reliability, and feasibility. RESULTS: Twenty neck pain patient (13 women)
      videos were assessed. Intra-and inter-rater reliability was substantial to almost
      perfect (ICC 0.76-1.00; SEM < 0.01-2.50). Feasibility was moderate to almost
      perfect (ICC 0.54-1; SEM <  0.01-2.98). CONCLUSIONS: Video (slow motion) ratings
      of time and errors for F8 and ZZ movement patterns in neck pain subjects showed
      high intra and inter-rater reliability. Achieving reliable ratings in clinic
      (real-time) appears feasible. Synthesising our results, the most reliable and
      feasible CMS ratings appear to be when the subject uses accurate rather than
      accurate and fast execution. The ZZ movement pattern may be superior to F8 in
      terms of rating. Time and error frequency for tracing F8 and ZZ as accurately as
      possible in determining CMS appears promising for use in clinic. Future research
      directions were identified.

PMID- 30290758
TI  - A draft genome of the striped catfish, Pangasianodon hypophthalmus, for
      comparative analysis of genes relevant to development and a resource for
      aquaculture improvement.
AB  - BACKGROUND: The striped catfish, Pangasianodon hypophthalmus, is a freshwater and
      benthopelagic fish common in the Mekong River delta. Catfish constitute a
      valuable source of dietary protein. Therefore, they are cultured worldwide, and
      P. hypophthalmus is a food staple in the Mekong area. However, genetic
      information about the culture stock, is unavailable for breeding improvement,
      although genetics of the channel catfish, Ictalurus punctatus, has been reported.
      To acquire genome sequence data as a useful resource for marker-assisted
      breeding, we decoded a draft genome of P. hypophthalmus and performed comparative
      analyses. RESULTS: Using the Illumina platform, we obtained both nuclear and
      mitochondrial DNA sequences. Molecular phylogeny using the mitochondrial genome
      confirmed that P. hypophthalmus is a member of the family Pangasiidae and is
      nested within a clade including the families Cranoglanididae and Ictaluridae. The
      nuclear genome was estimated at approximately 700 Mb, assembled into 568
      scaffolds with an N50 of 14.29 Mbp, and was estimated to contain ~ 28,600 protein
      coding genes, comparable to those of channel catfish and zebrafish.
      Interestingly, zebrafish produce gadusol, but genes for biosynthesis of this
      sunscreen compound have been lost from catfish genomes. The differences in gene
      contents between these two catfishes were found in genes for vitamin D-binding
      protein and cytosolic phospholipase A2, which have lost only in channel catfish.
      The Hox cluster in catfish genomes comprised seven paralogous groups, similar to
      that of zebrafish, and comparative analysis clarified catfish lineage-specific
      losses of A5a, B10a, and A11a. Genes for insulin-like growth factor (IGF)
      signaling were conserved between the two catfish genomes. In addition to
      identification of MHC class I and sex determination-related gene loci, the
      hypothetical chromosomes by comparison with the channel catfish demonstrated the
      usefulness of the striped catfish genome as a marker resource. CONCLUSIONS: We
      developed genomic resources for the striped catfish. Possible conservation of
      genes for development and marker candidates were confirmed by comparing the
      assembled genome to that of a model fish, Danio rerio, and to channel catfish.
      Since the catfish genomic constituent resembles that of zebrafish, it is likely
      that zebrafish data for gene functions is applicable to striped catfish as well.

PMID- 30290760
TI  - Detection of micro-metastases by flow cytometry in lymph nodes from patients with
      penile cancer.
AB  - BACKGROUND: The tumor draining lymph node concept was first described in penile
      cancer for staging. Immunohistochemistry and histopathology evaluations are
      routinely used in clinical practice to examine lymph nodes for metastasis.
      However, these methods are time-consuming with low diagnostic accuracy and micro
      metastases might be missed. In this study, we aim to evaluate detection of
      metastatic cells in draining lymph nodes by flow cytometry. METHODS: To assess
      the sensitivity of micro-metastasis detection by FACS (Fluorescence-activated
      cell sorting), HeLa cells were titrated into Peripheral blood mononuclear cells
      (PBMCs) and expression of pan-cytokeratin AE1/AE3 was analyzed. Single cell
      suspensions were separately prepared from 10 regional lymph nodes obtained from 5
      patients with invasive penile cancer undergoing radical surgery and lymph node
      dissection. Lymph node dereived cells were examined for cell surface expression
      of EpCAM, E-cadherin and intracellular expression of pan-cytokeratin AE1/AE3 by
      FACS. RESULTS: Ten lymph nodes from 5 penile cancer patients were investigated in
      a head-to-head comparison between FACS and pathology examination of sections. All
      metastatic lymph nodes verified by pathology examination were also identified by
      FACS. Two additional lymph nodes with micro-metastases were diagnosed by FACS
      only. CONCLUSIONS: FACS analyses of pan-cytokeratin AE1/AE3 stained single cells
      from tumor draining lymph nodes can be used to detect micro-metastases in
      patients with penile cancer patients.

PMID- 30290762
TI  - Three dimensional evaluation of soft tissue after orthognathic surgery.
AB  - BACKGROUND: To evaluate the nasolabial soft tissue change three-dimensionally
      after orthognathic surgery, using a structured light scanner. METHODS: Thirty-two
      malocclusion patients, who underwent orthognathic surgery, were evaluated. CBCT
      and 3D facial scans were obtained before surgery and 3 months after surgery. The
      3D changes in the 26 landmarks, and the relative ratio of the soft tissue
      movement to the bony movement, were evaluated. RESULTS: In the Le Fort I
      advancement patients, the nasal tip moved 17% forward, compared to the maxillary
      bony movement, but the nasal prominence decreased 15%. The alar width increased 4
      mm after the advancement, and the width decreased 4.7 mm after Le Fort I setback.
      The relative ratio of the soft tissue movement to the bony movement after
      bilateral sagittal split osteotomy was about 66% at the Li point in the
      anteroposterior direction, and it was 21% in the Le Fort I advancement and 14% in
      Le Fort I setback at the Ls point. CONCLUSION: Alar cinch suturing may not be
      sufficient to overcome the effect of the maxilla advancement compressing the
      nasal complex. Alar width widening was prevented in Le Fort I setback. However,
      it is uncertain that the alar cinch suturing was solely responsible. The soft
      tissue around the mandible tends to accompany the bony movement more than the
      maxillary area. In addition, structured light scanning system proved to be a
      useful tool to evaluate the nasolabial soft tissue.

PMID- 30290761
TI  - Tunneling nanotubes evoke pericyte/endothelial communication during normal and
      tumoral angiogenesis.
AB  - BACKGROUND: Nanotubular structures, denoted tunneling nanotubes (TNTs) have been
      described in recent times as involved in cell-to-cell communication between
      distant cells. Nevertheless, TNT-like, long filopodial processes had already been
      described in the last century as connecting facing, growing microvessels during
      the process of cerebral cortex vascularization and collateralization. Here we
      have investigated the possible presence and the cellular origin of TNTs during
      normal brain vascularization and also in highly vascularized brain tumors.
      METHODS: We searched for TNTs by high-resolution immunofluorescence confocal
      microscopy, applied to the analysis of 20-um, thick sections from lightly fixed,
      unembedded samples of both developing cerebral cortex and human glioblastoma
      (GB), immunolabeled for endothelial, pericyte, and astrocyte markers, and vessel
      basal lamina molecules. RESULTS: The results revealed the existence of pericyte
      derived TNTs, labeled by proteoglycan NG2/CSPG4 and CD146. In agreement with the
      described heterogeneity of these nanostructures, ultra-long (> 300 um) and very
      thin (< 0.8 um) TNTs were observed to bridge the gap between the wall of distant
      vessels, or were detected as short (< 300 um) bridging cables connecting a vessel
      sprout with its facing vessel or two apposed vessel sprouts. The pericyte origin
      of TNTs ex vivo in fetal cortex and GB was confirmed by in vitro analysis of
      brain pericytes, which were able to form and remained connected by typical TNT
      structures. CONCLUSIONS: None of the multiple roles described for TNTs can be
      excluded from a possible involvement during the processes of both normal and
      pathological vessel growth. A possible function, suggested by the pioneering
      studies made during cerebral cortex vascularization, is in cell searching and
      cell-to-cell recognition during the processes of vessel collateralization and
      vascular network formation. According to our results, it is definitely the
      pericyte-derived TNTs that seem to actively explore the surrounding
      microenvironment, searching for (site-to-site recognition), and connecting with
      (pericyte-to-pericyte and/or pericyte-to-endothelial cell communication), the
      targeted vessels. This idea implies that TNTs may have a primary role in the very
      early phases of both physiological and tumor angiogenesis in the brain.

PMID- 30290763
TI  - Involvement of K+ATP and Ca2+ channels in hydrogen sulfide-suppressed ageing of
      porcine oocytes.
AB  - BACKGROUND: Hydrogen sulfide has been shown to improve the quality of oocytes
      destined for in vitro fertilization. Although hydrogen sulfide is capable of
      modulating ion channel activity in somatic cells, the role of hydrogen sulfide in
      gametes and embryos remains unknown. Our observations confirmed the hypothesis
      that the KATP and L-type Ca2+ ion channels play roles in porcine oocyte ageing
      and revealed a plausible contribution of hydrogen sulfide to the modulation of
      ion channel activity. RESULTS: We confirmed the benefits of the activation and
      suppression of the KATP and L-type Ca2+ ion channels, respectively, for the
      preservation of oocyte quality. CONCLUSIONS: Our experiments identified hydrogen
      sulfide as promoting the desired ion channel activity, with the capacity to
      protect porcine oocytes against cell death. Further experiments are needed to
      determine the exact mechanism of hydrogen sulfide in gametes and embryos.

PMID- 30290764
TI  - Genome-wide association scan for heterotic quantitative trait loci in multi-breed
      and crossbred beef cattle.
AB  - BACKGROUND: Heterosis has been suggested to be caused by dominance effects. We
      performed a joint genome-wide association analysis (GWAS) using data from multi
      breed and crossbred beef cattle to identify single nucleotide polymorphisms
      (SNPs) with significant dominance effects associated with variation in growth and
      carcass traits and to understand the mode of action of these associations.
      METHODS: Illumina BovineSNP50 genotypes and phenotypes for 11 growth and carcass
      traits were available for 6796 multi-breed and crossbred beef cattle. After
      performing quality control, 42,610 SNPs and 6794 animals were used for further
      analyses. A single-SNP GWAS for the joint association of additive and dominance
      effects was conducted in purebred, crossbred, and combined datasets using the
      ASReml software. Genomic breed composition predicted from admixture analyses was
      included in the mixed effect model to account for possible population
      stratification and breed effects. A threshold of 10% genome-wide false discovery
      rate was applied to declare associations as significant. The significant SNPs
      with dominance association were mapped to their corresponding genes at 100 kb.
      RESULTS: Seven SNPs with significant dominance associations were detected for
      birth weight, weaning weight, pre-weaning daily gain, yearling weight and
      marbling score across the three datasets at a false discovery rate of 10%. These
      SNPs were located on bovine chromosomes 1, 3, 4, 6 and 21 and mapped to six
      putative candidate genes: U6atac, AGBL4, bta-mir-2888-1, REPIN1, ICA1 and NXPH1.
      These genes have interesting biological functions related to the regulation of
      gene expression, glucose and lipid metabolism and body fat mass. For most of the
      identified loci, we observed over-dominance association with the studied traits,
      such that the heterozygous individuals at any of these loci had greater genotypic
      values for the trait than either of the homozygous individuals. CONCLUSIONS: Our
      results revealed very few regions with significant dominance genetic effects
      across all the traits studied in the three datasets used. Regarding the SNPs that
      were detected with dominance associations, further investigation is needed to
      determine their relevance in crossbreeding programs assuming that dominance
      effects are the main cause of (or contribute usefully to) heterosis.

PMID- 30290765
TI  - Modified Robert Jones bandage can not reduce postoperative swelling in enhanced
      recovery after primary total knee arthroplasty without intraoperative tourniquet:
      a randomized controlled trial.
AB  - BACKGROUND: Compression therapy is commonly used to reduce lower limb swelling
      and blood loss after knee surgery. This study was performed to investigate
      whether modified Robert Jones bandage (MRJB) as a postoperative compression
      therapy is necessary for enhanced-recovery primary total knee arthroplasty
      without the tourniquet application. METHODS: In this prospective randomized
      controlled trial, 90 patients were grouped into 2 groups randomly. The
      experimental group received compression therapy with MRJB from toes to thigh for
      24 h and the control group received no compression therapy. Knee swelling, blood
      loss, range of motion (ROM), pain, patient reported comfort level and
      complications were recorded. RESULTS: No significant differences were observed
      between the two groups when we compared knee swelling. Similarly, no significant
      difference on postoperative blood loss, pain, ROM, complications was found.
      However, patients in control group had significantly higher comfort ratings than
      compression group during the first 24 h. CONCLUSIONS: MRJB is not routinely
      indicated in enhanced-recovery primary total knee arthroplasty without tourniquet
      application. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical
      Trial Registry ( ChiCTR-INR-16010177 ) dated 18th December 2016.

PMID- 30290766
TI  - Impact of cardiac catheterization timing and contrast media dose on acute kidney
      injury after cardiac surgery.
AB  - BACKGROUND: The association between pre-operative cardiac catheterization and
      cardiac surgery associated acute kidney injury (CSA-AKI) has been reported
      inconsistently. The purpose of this study is to evaluate the effect of the
      catheterization timing and contrast media dose on the incidence of postoperative
      acute kidney injury. METHODS: Patients who underwent cardiac catheterization and
      cardiac surgery successively from January 2015 to December 2015 were
      prospectively enrolled in this study. The primary outcome was CSA-AKI which was
      defined as the Kidney Disease: Improving Global Outcomes Definition and Staging
      (KDIGO) criteria. Univariate analysis and multivariate regression were performed
      to identify the predictors for CSA-AKI. Baseline characteristics were balanced
      with propensity score method for better adjustment. RESULTS: A total of 1069
      consecutive eligible patients were enrolled into this study. The incidence of CSA
      AKI and AKI requiring renal replacement therapy (AKI-RRT) were 38.5% (412/1069)
      and 1.9% (20/1069) respectively. Preoperative estimated glomerular filtration
      rate less than 60 mL/min/1.73m2 (OR = 2.843 95% CI 1.374-5.882), the time
      interval between catheterization and surgery<=7 days (OR = 2.546, 95% CI 1.548
      4.189) and the dose of contrast media (CM) > 240 mg/kg (OR = 2.490, 95%CI 1.392
      4.457) were identified as predictors for CSA-AKI. In the patients with the dose
      of CM > 240 mg/kg, the incidence of CSA-AKI was higher in patients who underwent
      cardiac catheterization <=7 days before cardiac surgery than in those of > 7 days
      before cardiac surgery (39.4% vs. 28.8%, p = 0.025). The longer interval of more
      than 7 days was revealed to be inversely associated with CSA-AKI through logistic
      regression (OR = 0.579, 95% CI 0.337-0.994). CONCLUSION: Catheterization within 7
      days of cardiac surgery and a dose of CM > 240 mg/kg were associated with the
      onset of CSA-AKI. For patients who received a dose of CM > 240 mg/kg, postponing
      the cardiac surgery is potentially beneficial to reduce the risk of CSA-AKI.

PMID- 30290767
TI  - Involvement of a dihydrodipicolinate synthase gene (FaDHDPS1) in fungal
      development, pathogenesis and stress responses in Fusarium asiaticum.
AB  - BACKGROUND: Dihydrodipicolinate synthase (DHDPS) is an allosteric enzyme, which
      catalyzes the first unique step of lysine biosynthesis in prokaryotes, higher
      plants and some fungi. To date, the biological roles of DHDPS in filamentous
      fungi are poorly understood. RESULTS: In this study, on the basis of comparative
      genome resequencing, a DHDPS gene was found to be specific in Fusarium asiaticum,
      named FaDHDPS1, which showed high amino acid identity to that of entomopathogenic
      fungus. Subcellular localization of the FaDHDPS1-GFP fusion protein was mainly
      concentrated in the cytoplasm of conidia and dispersed in the cytoplasm during
      conidial germination. To reveal the biological functions, both deletion and
      complementation mutants of FaDHDPS1 were generated. The results showed that the
      FaDHDPS1 deletion mutant was defective in conidiation, virulence and DON
      biosynthesis. In addition, deletion of FaDHDPS1 resulted in tolerance to sodium
      pyruvate, lysine, low temperature and Congo red. CONCLUSION: Results of this
      study indicate that FaDHDPS1 plays an important role in the regulation of
      vegetative differentiation, pathogenesis and adaption to multiple stresses in F.
      asiaticum.

PMID- 30290768
TI  - Potentially inappropriate medication use among hypertensive older African
      American adults.
AB  - BACKGROUND: Inappropriate use of medications, particularly among minority older
      adults with co-morbidity, remains a major public health concern. The American
      Geriatrics Society (AGS) reports that Potentially Inappropriate Medication (PIM)
      continues to be prescribed for older adults, despite evidence of poor outcomes.
      The main objective of this study was to examine the prevalence of PIM use among
      underserved non-institutionalized hypertensive older African-American adults.
      Furthermore, this study examines potential correlations between PIM use and the
      number and type of chronic conditions. METHODS: This cross-sectional study is
      comprised of a convenience sample of 193 hypertensive non-institutionalized
      African-American adults, aged 65 years and older recruited from several senior
      housing units located in underserved areas of South Los Angeles. The updated 2015
      AGS Beers Criteria was used to identify participants using PIMs. RESULTS: Almost
      one out of two participants had inappropriate medication use. While the average
      number of PIMs taken was 0.87 drugs, the range was from one to seven medications.
      Almost 23% of PIMs were due to drugs with potential drug-drug interactions. The
      most common PIM was the use of proton pump inhibitors (PPI) and Central Nervous
      System (CNS) active agents. Nearly 56% of PIMs potentially increased the risk of
      falls and fall-associated bone fractures. The use of PIMs was significantly
      higher among participants who reported a higher number of chronic conditions.
      Nearly 70% of participants with PIM use reported suffering from chronic pain.
      CONCLUSIONS: The major reason for high levels of polypharmacy, PIMs, and drug
      interactions is that patients suffer from multiple chronic conditions. But it may
      not be possible or necessary to treat all chronic conditions. Therefore, the
      goals of care should be explicitly reviewed with the patient in order to
      determine which of the many chronic conditions has the greatest impact on the
      life goals and/or functional priorities of the patient. Those drugs that have a
      limited impact on the patient's functional priorities and that may cause harmful
      drug-drug interactions can be reduced or eliminated, while the remaining
      medications can focus on the most important functional priorities of the patient.

PMID- 30290769
TI  - Missed opportunities in antenatal care for improving the health of pregnant women
      and newborns in Geita district, Northwest Tanzania.
AB  - BACKGROUND: Despite the significant benefits of early detection and management of
      pregnancy related complications during antenatal care (ANC) visits, not all
      pregnant women in Tanzania initiate ANC in a timely manner. The primary
      objectives of this research study in rural communities of Geita district,
      Northwest Tanzania were: 1) to conduct a population-based study that examined the
      utilization and availability of ANC services; and 2) to explore the challenges
      faced by women who visited ANC clinics and barriers to utilization of ANC among
      pregnant women. METHODS: A sequential explanatory mixed method design was
      utilized. Household surveys that examined antenatal service utilization and
      availability were conducted in 11 randomly selected wards in Geita district. One
      thousand, seven hundred and nineteen pregnant women in their 3rd trimester
      participated in household surveys. It was followed by focus group discussions
      with community health workers and pregnant women that examined challenges and
      barriers to ANC. RESULTS: Of the pregnant women who participated, 86.74% attended
      an ANC clinic at least once; 3.62% initiated ANC in the first trimester; 13.26%
      had not initiated ANC when they were interviewed in their 3rd trimester. Of the
      women who had attended ANC at least once, the majority (82.96%) had been checked
      for HIV status, less than a half (48.36%) were checked for hemoglobin level, and
      only a minority had been screened for syphilis (6.51%). Among women offered
      laboratory testing, the prevalence of HIV was 3.88%, syphilis, 18.57%, and
      anemia, 54.09%. In terms of other preventive measures, 91.01% received a tetanus
      toxoid vaccination, 76.32%, antimalarial drugs, 65.13%, antihelminthic drugs, and
      76.12%, iron supplements at least once. Significant challenges identified by
      women who visited ANC clinics included lack of male partner involvement, informal
      regulations imposed by health care providers, perceived poor quality of care, and
      health care system related factors. Socio-cultural beliefs, fear of HIV testing,
      poverty and distance from health clinics were reported as barriers to early ANC
      utilization. CONCLUSION: Access to effective ANC remains a challenge among women
      in Geita district. Notably, most women initiated ANC late and early initiation
      did not guarantee care that could contribute to better pregnancy outcomes.

PMID- 30290770
TI  - Genome-wide analysis of the plant-specific PLATZ proteins in maize and
      identification of their general role in interaction with RNA polymerase III
      complex.
AB  - BACKGROUND: PLATZ proteins are a novel class of plant-specific zinc-dependent DNA
      binding proteins that are classified as transcription factors (TFs). However,
      their common biochemical features and functions are poorly understood. RESULT:
      Here, we identified and cloned 17 PLATZ genes in the maize (Zea mays) genome. All
      ZmPLATZs were located in nuclei, consistent with their predicted role as TFs.
      However, none of ZmPLATZs was found to have intrinsic activation properties in
      yeast. Our recent work shows that FL3 (ZmPLATZ12) interacts with RPC53 and TFC1,
      two critical factors in the RNA polymerase III (RNAPIII) transcription complex.
      Using the yeast two-hybrid assay, we determined that seven other PLATZs
      interacted with both RPC53 and TFC1, whereas three had no protein-protein
      interaction with these two factors. The other six PLATZs interacted with either
      RPC53 or TFC1. These findings indicate that ZmPLATZ proteins are generally
      involved in the modulation of RNAPIII-mediated small non-coding RNA
      transcription. We also identified all of the PLATZ members in rice (Oryza sativa)
      and Arabidopsis thaliana and constructed a Maximum likelihood phylogenetic tree
      for ZmPLATZs. The resulting tree included 44 members and 5 subfamilies.
      CONCLUSIONS: This study provides insight into understanding of the phylogenetic
      relationship, protein structure, expression pattern and cellular localization of
      PLATZs in maize. We identified nine and thirteen ZmPLATZs that have protein
      protein interaction with RPC53 and TFC1 in the current study, respectively.
      Overall, the characterization and functional analysis of the PLATZ family in
      maize will pave the way to understanding RNAPIII-mediated regulation in plant
      development.

PMID- 30290771
TI  - Decoupling photo- and thermoperiod by projected climate change perturbs bud
      development, dormancy establishment and vernalization in the model tree Populus.
AB  - BACKGROUND: The performance and survival of deciduous trees depends on their
      innate ability to anticipate seasonal change. A key event is the timely
      production of short photoperiod-induced terminal and axillary buds that are
      dormant and freezing-tolerant. Some observations suggest that low temperature
      contributes to terminal bud initiation and dormancy. This is puzzling because low
      temperatures in the chilling range universally release dormancy. It also raises
      the broader question if the projected climate instabilities, as well as the
      northward migration of trees, will affect winter preparations and survival of
      trees. RESULTS: To gauge the response capacity of trees, we exposed juvenile
      hybrid aspens to a 10-h short photoperiod in combination with different day/night
      temperature regimes: high (24/24  degrees C), moderate (18/18  degrees C),
      moderate-low (18/12  degrees C) and low (12/12  degrees C), and analysed bud
      development, dormancy establishment, and marker gene expression. We found that
      low temperature during the bud formation period (pre-dormancy) upregulated
      dormancy-release genes of the gibberellin (GA) pathway, including the key GA
      biosynthesis genes GA20oxidase and GA3oxidase, the GA-receptor gene GID1, as well
      as GA-inducible enzymes of the 1,3-beta-glucanase family that degrade callose at
      plasmodesmal Dormancy Sphincter Complexes. Simultaneously, this pre-dormancy low
      temperature perturbed the expression of flowering pathway genes, including CO,
      FT, CENL1, AGL14, LFY and AP1. In brief, pre-dormancy low temperature compromised
      bud development, dormancy establishment, and potentially vernalization. On the
      other hand, a high pre-dormancy temperature prevented dormancy establishment and
      resulted in flushing. CONCLUSIONS: The results show that pre-dormancy low
      temperature represents a form of chilling that antagonizes dormancy
      establishment. Combined with available field data, this indicates that natural
      Populus ecotypes have evolved to avoid the adverse effects of high and low
      temperatures by initiating and completing dormant buds within an approximate
      temperature-window of 24-12  degrees C. Global warming and erratic temperature
      patterns outside this range can therefore endanger the successful propagation of
      deciduous perennials.

PMID- 30290772
TI  - Discovery of rare ancestry-specific variants in the fetal genome that confer risk
      of preterm premature rupture of membranes (PPROM) and preterm birth.
AB  - BACKGROUND: Preterm premature rupture of membranes (PPROM) is the leading
      identifiable cause of preterm birth, a complication that is more common in
      African Americans. Attempts to identify genetic loci associated with preterm
      birth using genome-wide association studies (GWAS) have only been successful with
      large numbers of cases and controls, and there has yet to be a convincing genetic
      association to explain racial/ethnic disparities. Indeed, the search for ancestry
      specific variants associated with preterm birth has led to the conclusion that
      spontaneous preterm birth could be the consequence of multiple rare variants. The
      hypothesis that preterm birth is due to rare genetic variants that would go
      undetected in standard GWAS has been explored in the present study. The detection
      and validation of these rare variants present challenges because of the low
      allele frequency. However, some success in the identification of fetal loci/genes
      associated with preterm birth using whole genome sequencing and whole exome
      sequencing (WES) has recently been reported. While encouraging, this is currently
      an expensive technology, and methods to leverage the sequencing data to quickly
      identify and cost-effectively validate variants are needed. METHODS: We developed
      a WES data analysis strategy based on neonatal genomic DNA from PPROM cases and
      term controls that was unencumbered by preselection of candidate genes, and
      capable of identifying variants in African Americans worthy of focused evaluation
      to establish statistically significant associations. RESULTS: We describe this
      approach and the identification of damaging nonsense variants of African ancestry
      in the DEFB1 and MBL2 genes that encode anti-microbial proteins that presumably
      defend the fetal membranes from infectious agents. Our approach also enabled us
      to rule out a likely contribution of a predicted damaging nonsense variant in the
      METTL7B gene. CONCLUSIONS: Our findings support the notion that multiple rare
      population-specific variants in the fetal genome contribute to preterm birth
      associated with PPROM.

PMID- 30290774
TI  - Impact of the epidermal growth factor receptor mutation status on the prognosis
      of recurrent adenocarcinoma of the lung after curative surgery.
AB  - BACKGROUND: The prognosis of patients with epidermal growth factor receptor
      (EGFR) mutant adenocarcinoma of the lung (Mt) and EGFR wild-type adenocarcinoma
      (Wt) after complete resection of the lung differ; however, the mechanisms
      responsible for these differences remain unclear. The present study examined the
      post-operative prognosis of recurrent pulmonary adenocarcinoma patients to
      evaluate the clinicopathological nature of Mt and contribution of EGFR - tyrosine
      kinase inhibitors (TKI) to the prognosis of patients. METHODS: The subjects were
      237 patients with recurrent pulmonary adenocarcinoma who underwent EGFR mutation
      analysis, and consisted of 108 patients with recurrent Mt and 129 with recurrent
      Wt. Multivariate analyses were performed to investigate whether the EGFR status
      is a prognostic factor for relapse-free survival (RFS) and post-relapse survival
      (PRS). RESULTS: RFS was significantly better in Mt than in Wt patients; median
      RFS were 20.2 and 13.3 months, respectively (p < 0.001). The multivariate
      analysis identified EGFR mutation as an independent prognostic factor for a
      favorable RFS (hazard ratio = 0.68; 95% confidence interval, 0.52-0.89).
      Although, no significant differences were observed in PRS between Mt and Wt
      patients (median PRS were 33.9 and 28.2 months, respectively; p = 0.360), PRS was
      significantly better in Mt with EGFR - TKI than in Wt and Mt patients without
      EGFR - TKI (p = 0.008 and p < 0.001, respectively). PRS was also significantly
      better in Wt than in Mt patients without EGFR - TKI (p < 0.001). The multivariate
      analysis identified the administration of EGFR - TKI as an independent prognostic
      factor for PRS (hazard ratio = 0.60; 95% confidence interval, 0.40-0.89).
      CONCLUSIONS: EGFR mutation tumors were associated with a significantly better RFS
      for recurrent pulmonary adenocarcinoma after curative resection of the lung,
      which represented the less aggressive nature of Mt tumors. However, patients with
      Mt did not have a favorable prognosis after recurrence unless they received EGFR 
      TKI.

PMID- 30290773
TI  - Preoperative oral antibiotic prophylaxis reduces Pseudomonas aeruginosa surgical
      site infections after elective colorectal surgery: a multicenter prospective
      cohort study.
AB  - BACKGROUND: Healthcare-associated infections caused by Pseudomonas aeruginosa are
      associated with poor outcomes. However, the role of P. aeruginosa in surgical
      site infections after colorectal surgery has not been evaluated. The aim of this
      study was to determine the predictive factors and outcomes of surgical site
      infections caused by P. aeruginosa after colorectal surgery, with special
      emphasis on the role of preoperative oral antibiotic prophylaxis. METHODS: We
      conducted an observational, multicenter, prospective cohort study of all patients
      undergoing elective colorectal surgery at 10 Spanish hospitals (2011-2014). A
      logistic regression model was used to identify predictive factors for P.
      aeruginosa surgical site infections. RESULTS: Out of 3701 patients, 669 (18.1%)
      developed surgical site infections, and 62 (9.3%) of these were due to P.
      aeruginosa. The following factors were found to differentiate between P.
      aeruginosa surgical site infections and those caused by other microorganisms:
      American Society of Anesthesiologists' score III-IV (67.7% vs 45.5%, p = 0.001,
      odds ratio (OR) 2.5, 95% confidence interval (95% CI) 1.44-4.39), National
      Nosocomial Infections Surveillance risk index 1-2 (74.2% vs 44.2%, p < 0.001, OR
      3.6, 95% CI 2.01-6.56), duration of surgery >=75thpercentile (61.3% vs 41.4%, p =
      0.003, OR 2.2, 95% CI 1.31-3.83) and oral antibiotic prophylaxis (17.7% vs 33.6%,
      p = 0.01, OR 0.4, 95% CI 0.21-0.83). Patients with P. aeruginosa surgical site
      infections were administered antibiotic treatment for a longer duration (median
      17 days [interquartile range (IQR) 10-24] vs 13d [IQR 8-20], p = 0.015, OR 1.1,
      95% CI 1.00-1.12), had a higher treatment failure rate (30.6% vs 20.8%, p = 0.07,
      OR 1.7, 95% CI 0.96-2.99), and longer hospitalization (median 22 days [IQR 15-42]
      vs 19d [IQR 12-28], p = 0.02, OR 1.1, 95% CI 1.00-1.17) than those with surgical
      site infections due to other microorganisms. Independent predictive factors
      associated with P. aeruginosa surgical site infections were the National
      Nosocomial Infections Surveillance risk index 1-2 (OR 2.3, 95% CI 1.03-5.40) and
      the use of oral antibiotic prophylaxis (OR 0.4, 95% CI 0.23-0.90). CONCLUSIONS:
      We observed that surgical site infections due to P. aeruginosa are associated
      with a higher National Nosocomial Infections Surveillance risk index, poor
      outcomes, and lack of preoperative oral antibiotic prophylaxis. These findings
      can aid in establishing specific preventive measures and appropriate empirical
      antibiotic treatment.

PMID- 30290775
TI  - Risk factors for paclitaxel-induced peripheral neuropathy in patients with breast
      cancer.
AB  - BACKGROUND: Paclitaxel induced peripheral neuropathy (PIPN) is a major
      debilitating side effect of paclitaxel in patients with breast cancer with no
      fully known mechanisms. The aim of the study was to find out the possible risk
      factors for PIPN. METHODS: Eligible patients with node positive breast cancer
      undergoing chemotherapy with paclitaxel were assessed. They belonged to an
      initial randomized controlled trial in which the effectiveness of omega-3 fatty
      acids in preventing and reducing severity of PIPN was evaluated (protocol ID:
      NCT01049295). Reduced total neuropathy score (r-TNS) was used for measuring PIPN.
      All analyses were performed adjusting for intervention effect. The association
      between age, BMI, BSA, pathological grade, molecular biomarkers and PIPN was
      evaluated. RESULTS: Fifty-seven patients with breast cancer were investigated.
      Age was significantly associated with risk of PIPN (RR:1.50, P value = .024).
      Body mass index and BSA had significant association with severity of PIPN
      (B:1.28, P = .025; and B: 3.88, P = .010 respectively). Also, BSA showed a
      significant association with the risk of PIPN (RR: 2.28, P = .035; B: 3.88, P =
      .035). Incidence and severity of PIPN were much more pronounced in progesterone
      receptor positive (PR+) patients (RR:1.88, P = .015 and B:1.54, P = .012).
      Multivariate analysis showed that age and the status of PR+ were independent risk
      factor for incidence and the status of PR+ was the only independent risk factor
      for severity of PIPN. CONCLUSION: Age, BSA and the status of PR+, should be
      considered as the risk factors for PIPN before commencement of chemotherapy with
      paclitaxel in patients with breast cancer. Older patients, those with greater BSA
      and PR+ patients may need closer follow up and more medical attention due to
      greater incidence and severity of PIPN.

PMID- 30290776
TI  - An exploratory analysis of the interactions between social norms and the built
      environment on cycling for recreation and transport.
AB  - BACKGROUND: There is growing evidence of the public health benefits of promoting
      cycling. The ways that the built environment and perceived social norms
      independently influence cycling participation is well established. However,
      whether these factors interact to influence cycling participation has not been
      examined. Such research is important because understanding the effect of multiple
      socio-ecological factors and the interactions between them is needed to guide the
      development of interventions and strategies to increase cycling participation.
      Therefore, the aim of this study is to explore the interactive effects of the
      built environment and perceived social norms on transport and recreational
      cycling. METHODS: Data was collected using a self-administered online
      questionnaire from 228 office workers in Metropolitan Melbourne, Australia.
      Measures used in previous research were employed to assess self-reported
      transport and recreation cycling in the last week, perceptions of neighbourhood
      built environment, perceived social norms towards cycling, and objective land-use
      mix, residential density and street connectivity of the suburbs in which
      participants lived and work. Multiple binary logistic regression analyses were
      conducted to explore the interactive effects of the built environment and
      perceived social norms on transport and recreation cycling. All interactive
      effects were considered significant at p < 0.10. RESULTS: There was a significant
      interactive effect between the workplace built environment and perceived group
      norm on transport cycling (p = 0.06). There were no other significant interactive
      effects observed between components of the built environment and perceived social
      norms on transport or recreational cycling. CONCLUSIONS: The interactive effect
      found in this study provides some evidence that the workplace built environment
      interacts with perceived group norms to influence cycling for transport. Positive
      perceptions of the workplace built environment, such as showers and secure bike
      racks, can somewhat compensate for the negative influence of when cycling is
      considered less of a norm among, family, friend or colleagues. However, the
      findings of this study did not support that the neighbourhood built environment
      and perceived social norms interact to influence cycling for recreation or
      transport. These findings contribute to the knowledge of how multiple factors may
      reciprocate to influence individual's decision to cycle. More research into the
      interactive effects of socio-ecological factors is warranted.

PMID- 30290778
TI  - Long-term desensitization for ABO-incompatible living related kidney
      transplantation recipients with high refractory and rebound anti-blood type
      antibody: case report.
AB  - BACKGROUND: ABO-incompatible living related kidney transplantation (ABO-iLKT) has
      increased the possibilities for kidney transplantation in patients with end stage
      renal disease. Due to advancements in immunosuppressive agents and the
      identification of immunological conditions following ABO-iLKT, this
      transplantation technique has achieved the same success rate as ABO-compatible
      LKT. However, some patients continue to generate anti-blood type antibodies,
      despite conventional immunosuppressant treatment. CASE PRESENTATION: A 60-year
      old man was referred to our hospital for kidney transplantation. The proposed
      transplant was ABO incompatible, from a donor with blood-type A to a recipient
      with blood-type O. The recipient's anti-A blood-type IgG antibody titer was
      measured at 4096-fold dilution. Following desensitization therapy, including
      mycophenolate mofetil (MMF) 750 mg/day for 3 months, intravenous Rituximab 200
      mg, and two sessions of double filtration plasmapheresis, the anti-A blood-type
      IgG antibody titer decreased to only 516-fold dilution and did not meet our
      target of less than 128-fold dilution. MMF was thus continued for an additional 4
      months and four additional sessions of plasmapheresis were undertaken. Following
      these interventions, antibody titers decreased to 128-fold dilution and ABO-iLKT
      was performed. Following transplant, antibody-mediated rejection was not observed
      and renal function was preserved. However, a post-operative renal biopsy 1.5
      months later showed evidence of T-cell-mediated rejection IB. The patient was
      treated with steroids, with no increase in serum creatinine. CONCLUSION: Our
      findings suggest that the long-term single MMF desensitization therapy could be a
      suitable option for ABO-iLKT with high refractory and rebound anti-blood type
      antibody. Further studies are required to establish the optimal immunosuppression
      regimen to control B cell- mediated immunity in ABO-iLKT.

PMID- 30290779
TI  - Conventional immunosuppressive therapy in severe Behcet's Uveitis: the switch
      rate to the biological agents.
AB  - BACKGROUND: To report the switch rate of conventional immunosuppressive (CIS)
      therapies to the biological agents (BA) in patients with refractory Behcet's
      uveitis (BU). METHODS: In this retrospective study, clinical records were
      reviewed of 76 patients' 116 eyes presenting with BU who had been treated with
      immunosuppressive drug therapy. Mann Whitney U test was used for the intergroup
      comparisons of parameters without normal distribution as well as calculation of
      descriptive statistical methods (mean, standard deviation, median, frequency and
      rate). Wilcoxon Signed Ranks test was used for the intragroup comparisons of
      parameters without normal distribution. Pearson's Chi-Square test and Fisher
      Freeman-Halton test were used for the comparisons of qualitative data. RESULTS:
      Except for one, all patients were first treated with CIS regimens for BU. Thirty
      one patients (41.3%) who were unresponsive to CIS regimens were switched to
      IFNalpha2a therapy. After that, eight of these cases were switched to the anti
      TNF-alpha treatments. The presence of initial ocular complications were found to
      be statistically higher in BA treated patients than the CIS treated cases (p <
      0.001). Both in CIS treated and in BA treated cases, an increase in visual acuity
      (VA) was observed during the last examination compared to the initial examination
      and was significant (p < 0.001 and p = 0.018, respectively). CONCLUSIONS: CIS
      treatment was found to be effective and safe, as suggested in the management
      guidelines for severe BU. Biological therapy was also found effective for the
      improvement of the VA. We observed that 58.7% of cases could be treated with
      strong immunosuppressive therapies, however, nearly half of the patients could
      have lost their VA if BAs were not existent. During the treatment course of
      severe cases with BU, classical therapy stage must still be protected as the
      first-line therapy due to the their reasonable activity and safety.

PMID- 30290777
TI  - Development of a 3D, networked multi-user virtual reality environment for home
      therapy after stroke.
AB  - BACKGROUND: Impairment of upper extremity function is a common outcome following
      stroke, to the detriment of lifestyle and employment opportunities. Yet, access
      to treatment may be limited due to geographical and transportation constraints,
      especially for those living in rural areas. While stroke rates are higher in
      these areas, stroke survivors in these regions of the country have substantially
      less access to clinical therapy. Home therapy could offer an important
      alternative to clinical treatment, but the inherent isolation and the monotony of
      self-directed training can greatly reduce compliance. METHODS: We developed a 3D,
      networked multi-user Virtual Environment for Rehabilitative Gaming Exercises
      (VERGE) system for home therapy. Within this environment, stroke survivors can
      interact with therapists and/or fellow stroke survivors in the same virtual space
      even though they may be physically remote. Each user's own movement controls an
      avatar through kinematic measurements made with a low-cost, KinectTM device. The
      system was explicitly designed to train movements important to rehabilitation and
      to provide real-time feedback of performance to users and clinicians. To obtain
      user feedback about the system, 15 stroke survivors with chronic upper extremity
      hemiparesis participated in a multisession pilot evaluation study, consisting of
      a three-week intervention in a laboratory setting. For each week, the participant
      performed three one-hour training sessions with one of three modalities: 1) VERGE
      system, 2) an existing virtual reality environment based on Alice in Wonderland
      (AWVR), or 3) a home exercise program (HEP). RESULTS: Over 85% of the subjects
      found the VERGE system to be an effective means of promoting repetitive practice
      of arm movement. Arm displacement averaged 350 m for each VERGE training session.
      Arm displacement was not significantly less when using VERGE than when using AWVR
      or HEP. Participants were split on preference for VERGE, AWVR or HEP.
      Importantly, almost all subjects indicated a willingness to perform the training
      for at least 2-3 days per week at home. CONCLUSIONS: Multi-user VR environments
      hold promise for home therapy, although the importance of reducing complexity of
      operation for the user in the VR system must be emphasized. A modified version of
      the VERGE system is currently being used in a home therapy study.

PMID- 30290781
TI  - Mineral and bone disorder management in hemodialysis patients: comparing PTH
      control practices in Japan with Europe and North America: the Dialysis Outcomes
      and Practice Patterns Study (DOPPS).
AB  - BACKGROUND: High-circulating level of parathyroid hormone (PTH) is associated
      with elevated mortality in dialysis patients. The Japanese Society for Dialysis
      Therapy guideline suggests a lower PTH target than other international
      guidelines; thus, PTH control may differ in Japan compared with other regions,
      and be associated with mortality. METHODS: We analyzed data from hemodialysis
      patients with >=3 measurements of PTH during the first 9 months after enrollment
      in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4-5 (2009
      2015). PTH control was assessed by the mean, slope, and mean squared error (MSE)
      of all PTH measurements over the 9-month run-in period. Distribution of each PTH
      control was assessed by regions (Europe/Australia/New Zealand [Eur/ANZ], Japan
      and North America) and dialysis vintage. Mortality rates were compared across PTH
      control categories using Cox regression models. RESULTS: Mean PTH was lower in
      Japan than in other regions across dialysis vintage categories. In patients with
      dialysis vintage < 90 days, PTH level was more likely to decline > 5% per month
      in Japan (48% of patients) versus Eur/ANZ (35%) and North America (35%). In
      patients with dialysis vintage > 1 year, Japanese patients maintained steady PTH,
      while patients in Eur/ANZ and North America were more likely to experience a PTH
      increase. Mean PTH was associated with mortality in the overall samples (highest
      mortality rate for PTH > 600 pg/mL, hazard ratio, 1.35; 95% confidence interval,
      1.20 to 1.52 vs PTH 200-399 pg/mL), and the association was obvious in the
      prevalent patients (hazard ratio, 1.44; 95% confidence interval, 1.26 to 1.65).
      PTH slope and MSE did not show significant association with mortality in the
      overall sample as well as in subjects stratified both by region and dialysis
      vintage. CONCLUSION: PTH control in hemodialysis patients, as measured by keeping
      a stable PTH level over 9 months, was observed in Japan contrasted with other
      regions. High PTH mean, but not increased PTH slope and MSE, was associated with
      mortality especially in prevalent patients.

PMID- 30290780
TI  - Genome-wide association study identifies loci and candidate genes for non
      idiopathic pulmonary hypertension in Eastern Chinese Han population.
AB  - BACKGROUND: Pulmonary hypertension (PH) is a rare disease characterized by
      proliferation and occlusion of small pulmonary arterioles, which has been
      associated with a high mortality rate. The pathogenesis of PH is complex and
      incompletely understood, which includes both genetic and environmental factors
      that alter vascular structure and function. METHODS: Thus we aimed to reveal the
      potential genetic etiology of PH by targeting 143 tag SNPs of 14 candidate genes.
      Totally 208 individuals from Chinese Han population were enrolled in the present
      study, including 109 non-idiopathic PH patients and 99 healthy controls. RESULTS:
      The data revealed that 2 SNPs were associated with PH overall susceptibility at p
      < 3*10- 4 after Bonferroni correction. The top hit was rs6557421 (p = 4.5*10- 9),
      located within Nox3 gene on chromosome 6. Another SNP rs3744439 located in Tbx4
      gene, also showed evidence of association with PH susceptibility (p = 1.2*10- 6).
      The distribution of genotype frequencies of rs6557421 and rs3744439 have dramatic
      differences between PH patients and controls. Individuals with rs6557421 TT
      genotype had a 10.72-fold/14.20-fold increased risk to develop PH when compared
      with GG or GG/GT carriers in codominant or recessive model, respectively (TT
      versus GG: 95%CI = 4.79-24.00; TT versus GG/GT: 95%CI = 6.65-30.33). As for
      rs3744439, AG genotype only occurred in healthy controls but has not been
      observed in PH patients. We further validated the result by using 26 different
      populations from five regions around the globe, including African (AFR), American
      (AMR), East Asian (EAS), European (EUR), and South Asian (SAS). In consistent
      with the present case-control study's results, significantly different genotype
      frequencies of the observed SNPs existed between PH patients and healthy
      individuals from all over the world. CONCLUSIONS: The results suggested that
      rs6557421 variant in Nox3 and rs3744439 variant in Tbx4 might have potential
      effect on individual susceptibility to pulmonary hypertension, which could lead
      to therapeutic or diagnosis approaches in PH.

PMID- 30290782
TI  - A qualitative study on the stigma experienced by people with mental health
      problems and epilepsy in the Philippines.
AB  - BACKGROUND: Stigma towards people with mental health problems (PMHP) is known to
      have substantial negative impacts on their lives. More in-depth exploration of
      the stigma and discrimination experienced by PMHP in low- and middle-income
      countries is needed. Previous research suggests that negative attitudes towards
      PMHP are widespread among the Filipino general public. However, no study has
      investigated PMHP's own experiences of being stigmatised in the Philippines.
      METHODS: A qualitative study was conducted on the stigma experienced by PMHP
      (including people with epilepsy) and its related factors in the Philippines,
      employing the constructivist grounded theory approach. We analysed data on 39
      PMHP collected through interviews with PMHP, their carers, and community health
      volunteers who know them well. RESULTS: The findings highlight the culturally and
      socio-economically specific contexts, consequences, and impact modifiers of
      experiences of stigma. Participants emphasised that PMHP face stigma because of
      the cultural traits such as the perception of mental health problem as a disease
      of the family and the tendency to be overly optimistic about the severity of the
      mental health problem and its impact on their life. Further, stigma was
      experienced under conditions where mental health care was not readily available
      and people in the local community could not resolve the PMHP's mental health
      crisis. Stigma experiences reduced social networks and opportunities for PMHP,
      threatened the economic survival of their entire family, and exacerbated their
      mental health problems. An individual's reaction to negative experiences can be
      fatalistic in nature (e.g. believing in it is God's will). This fatalism can help
      PMHP to remain hopeful. In addition, traditional communal unity alleviated some
      of the social exclusion associated with stigma. CONCLUSIONS: The study indicates
      that existing stigma-reduction strategies might have limitations in their
      effectiveness across cultural settings. Therefore, we propose context-specific
      practical implications (e.g. emphasis on environmental factors as a cause of
      mental health problems, messages to increase understanding not only of the
      possibility of recovery but also of challenges PMHP face) for the Philippines.

PMID- 30290783
TI  - Barriers to bowel scope (flexible sigmoidoscopy) screening: a comparison of non
      responders, active decliners and non-attenders.
AB  - BACKGROUND: Participation in bowel scope screening (BSS) is low (43%), limiting
      its potential to reduce colorectal cancer (CRC) incidence and mortality. This
      study aimed to quantify the prevalence of barriers to BSS and examine the extent
      to which these barriers differed according to non-participant profiles: non
      responders to the BSS invitation, active decliners of the invitation, and non
      attenders of confirmed appointments. METHODS: Individuals invited for BSS between
      March 2013 and December 2015, across 28 General Practices in England, were sent a
      questionnaire. Questions measured initial interest in BSS, engagement with the
      information booklet, BSS participation, and, where applicable, reasons for BSS
      non-attendance. Chi-square tests of independence were performed to examine the
      relationship between barriers, non-participant groups and socio-demographic
      variables. RESULTS: 1478 (45.8%) questionnaires were returned for analysis: 1230
      (83.2%) attended screening, 114 (7.7%) were non-responders to the BSS invitation,
      100 (6.8%) were active decliners, and 34 (2.3%) were non-attenders. Non
      responders were less likely to have read the whole information booklet than
      active decliners (x2 (2, N = 157) = 7.00, p = 0.008) and non-attenders (x2 (2, N
      = 101) = 8.07, p = 0.005). Non-responders also had lower initial interest in
      having BSS than either active decliners (x2 (2, N = 213) = 6.07, p = 0.014) or
      non-attenders (x2 (2, N = 146) = 32.93, p < 0.001). Overall, anticipated pain
      (33%) and embarrassment (30%) were the most commonly cited barriers to BSS
      participation. For non-attenders, however, practical, appointment-related reasons
      were most common (27%). CONCLUSIONS: Interventions to improve BSS uptake should
      be more nuanced and use targeted strategies to address the specific needs of each
      group.

PMID- 30290784
TI  - Hydrogel coils versus bare platinum coils for the endovascular treatment of
      intracranial aneurysms: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Recent studies have shown conflicting results regarding the effect of
      hydrogel coils for treating intracranial aneurysm compared to bare platinum
      coils. We implemented a meta-analysis to assess the value of hydrogel coils in
      intracranial aneurysm treatment. METHODS: The MEDLINE, EMBASE, and Cochrane
      Library databases were searched for randomized controlled trials (RCTs) which had
      evaluated hydrogel coils versus bare platinum coils for intracranial aneurysms.
      RESULTS: We pooled 1526 patients from 4 RCTs with the mean follow-up time of more
      than 16 months. Hydrogel coils had reductions on mid-term recurrence (RR 0.78,
      95% CI 0.65 to 0.94, P = 0.008) and residual aneurysm (RR 0.71, 95% CI 0.57 to
      0.88, P = 0.002), but didn't show any significant differences in other favorable
      outcomes such as functional recovery, mortality and so on. In the subgroup
      analysis, we found that second-generation hydrogel coils might exhibit potential
      impacts on increasing mid-term complete occlusion (RR 1.26, 95% CI 1.07 to 1.48,
      P = 0.005) and decreasing residual aneurysm neck. (RR 0.54, 95% CI 0.34 to 0.86,
      P = 0.010). CONCLUSIONS: Hydrogel coils showed no significant efficacy on
      functional recovery but exhibited a lower rate of recurrences and residual
      aneurysms in patients with intracranial aneurysms.

PMID- 30290785
TI  - "I'm used to doing it by myself": exploring self-reliance in pregnancy.
AB  - BACKGROUND: Self-reliance (the need to rely on one's own efforts and abilities)
      is cited as a potential coping strategy for decreased or absent social support
      during pregnancy. Little data exists on how women view self-reliance in
      pregnancy. METHODS: We recruited women from urban, walk-in pregnancy testing
      clinics from June 2014-June 2015. Women aged 16 to 44 and at less than 24 weeks
      gestational age were eligible. Participants completed an enrollment survey and in
      person, semi-structured interviews. We used framework analysis to identify key
      concepts and assess thematic relationships. RESULTS: Eighty-four English-speaking
      women completed qualitative interviews. Participants averaged 26 years of age and
      7 weeks estimated gestational age. Most identified as Black (54%) or Hispanic
      (20%), were unemployed or homemakers (52%), unmarried (92%), and had at least one
      child (67%). Most did not intend to get pregnant (61%) and planned to continue
      their pregnancy and parent (65%). We identified self-reliance as a prevalent
      concept that almost half (48%) of participants discussed in relationship to their
      pregnancy. Self-reliance in pregnancy consisted of several subthemes: 1) past
      experiences, 2) expectations of motherhood, 3) financial independence, 4)
      decision making, and 5) parenting. CONCLUSIONS: Self-reliance is an important
      aspect of women's reproductive lives and is threaded through women's past and
      current thoughts, feelings, experiences and decisions about pregnancy. Women's
      belief in their own self-reliance as well as a recognition of the limits of self
      reliance merits further research, especially as a potential strategy to cope with
      decreased or absent social support during pregnancy.

PMID- 30290786
TI  - Oral mucositis associated with anti-EGFR therapy in colorectal cancer: single
      institutional retrospective cohort study.
AB  - BACKGROUND: Chemotherapy-induced oral mucositis impairs the quality of life. The
      difference in severity of oral mucositis between different anti-epidermal growth
      factor receptor (EGFR) antibodies combined with cytotoxic drugs in colorectal
      cancer is unclear. The aim of this study was to investigate the differences in
      oral mucositis between panitumumab (Pmab) and cetuximab (Cmab) combined with 5
      fluorouracil (5-FU). METHODS: We conducted a retrospective cohort study. A total
      of 75 colorectal cancer outpatients treated with an anti-EGFR antibody combined
      with FOLFOX, FOLFIRI, or 5-FU/leucovorin as the first- to third-line treatment
      were included. The primary endpoint was the incidence of grade 2-3 oral
      mucositis. The secondary endpoint was the time to onset of oral mucositis. We
      also compared the incidence of toxicities of interest, skin toxicity,
      hypomagnesaemia and neutropenia, and time to treatment failure (TTF) between the
      two groups. RESULTS: Thirty-two patients treated with Pmab and 43 patients
      treated with Cmab were evaluated. Patient characteristics were similar between
      the two groups. The incidence of grade 2-3 oral mucositis was significantly
      higher with Pmab than with Cmab (31.3% vs 9.3%, P < 0.05). Moreover, the
      incidence of grade 3 oral mucositis was significantly higher in patients treated
      with Pmab (18.8% vs 0%, P < 0.01). The mean (SD) cycles to onset of the worst
      oral mucositis was 3.0 (2.9) in the Pmab group and 2.3 (1.7) in the Cmab group (P
      = 0.29). Oral mucositis was characterized by glossitis and cheilitis. The
      incidences of other toxicities were the following (Pmab vs Cmab): grade 2-3 skin
      toxicity: 68.8% vs 74.4% (P = 0.61), grade 2-3 hypomagnesaemia: 9.3% vs 7.0% (P =
      1.00), grade 3-4 neutropenia: 28.1% vs 37.2% (P = 0.46). The median TTF was not
      significantly different, i.e., 223 days vs 200 days (P = 0.39) for Pmab vs Cmab.
      CONCLUSIONS: Pmab-based chemotherapy resulted in significantly higher grades of
      oral mucositis compared with Cmab-based chemotherapy. The oral condition should
      be monitored carefully and early supportive care should be provided for patients
      treated with Pmab-based chemotherapy.

PMID- 30290787
TI  - Association between acromegaly and a single nucleotide polymorphism (rs2854744)
      in the IGFBP3 gene.
AB  - BACKGROUND: It has been reported that the single nucleotide polymorphism (SNP)
      rs2854744 at the - 202 locus of insulin-like growth factor binding protein-3
      (IGFBP3) is associated with serum levels and a number of malignancies. However,
      the effect of IGFBP3 gene polymorphism on acromegaly is less clear. Therefore, in
      the current study, we aimed to investigate whether the -202A/C polymorphism of
      IGFBP3 constitutes a risk factor for acromegaly. METHODS: The study included 102
      acromegalic patients and 143 control subjects in Beijing Tiantan Hospital. The
      genotyping of IGFBP3 was carried out using the MassARRAY method. Serum IGFBP3
      concentrations were also determined. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were used to evaluate the associations of genetic polymorphisms
      with the development of acromegaly and its different subtypes. RESULTS: The study
      revealed that the C allele of rs2854744 was associated with a reduced risk of
      acromegaly (OR 0.594, 95% CI 0.388-0.909), as well as with the female (OR 0.385,
      95% CI 0.206-0.72), macroadenoma (OR 0.557, 95% CI 0.347-0.893) and monotherapy
      (OR 0.512, 95% CI 0.316-0.828) subgroups under the additive model. A higher serum
      IGFBP3 level was observed in patients with the AA genotype, but this difference
      was not significant (P = 0.331). CONCLUSION: This study is one of the first to
      show that the IGFBP3 polymorphism may have an influence on serum levels and that
      the C allele of rs2854744 is associated with a reduced risk of acromegaly. This
      correlation was more prominent in females, those with large tumours and those
      treated with monotherapy in a Chinese population. Genetic polymorphism of IGFBP3
      may be involved in the development of acromegaly.

PMID- 30290788
TI  - Study of the reasons for the consumption of each type of vegetable within a
      population of school-aged children.
AB  - BACKGROUND: Several studies have evaluated the existence of factors that
      influence the consumption of vegetables in children, such as family environment,
      daily exposure to one or several vegetables, parents' consumption and consumption
      pattern and the way in which vegetables are prepared in the household, among
      others. The objective of this study was to investigate the reasons for
      consumption associated with each vegetable in school-aged children through a
      survey designed to be answered by the parents. METHODS: A preliminary study with
      162 parents was carried out on the consumption of vegetables in children aged 6
      to 12 years. Based on the information obtained, a survey was designed with 14
      phrases to investigate the reasons for the low consumption of each type of
      vegetable among school-aged children, which was answered online by 419 parents.
      RESULTS: The results obtained allowed us to categorise the vegetables into 6
      groups. Group A consisted of tomatoes, corn, pumpkin and carrots as the
      vegetables that children like to eat most. Group B contains the vegetables that
      are consumed mostly camouflaged in other preparations, such as onions and red
      peppers. Group C contains only cauliflower, which was negatively associated with
      senses, such as colour, smell and taste. This vegetable was never offered to
      children by a high percentage of parents. Group D consists of green vegetables:
      zucchini, spinach, chard and peas. Vegetables of this group are added to other
      foods and the child usually ingests them camouflaged or obliged. Group E consists
      of beetroot, lettuce and broccoli. Beetroot and lettuce were the vegetables
      parents reported were most often rejected by their children. This rejection, they
      stated, was due to sensory aspects, such as colour, texture and taste.
      CONCLUSIONS: The reasons for consumption among school-aged children depend on
      each type of vegetable and cannot be generalized. The sensory characteristics of
      the vegetable (mainly colour and flavour) and the habits of consumption in the
      family environment play a major role in children's acceptance or rejection of
      vegetables.

PMID- 30290789
TI  - Salivary cortisol in post-traumatic stress disorder: a systematic review and meta
      analysis.
AB  - BACKGROUND: Studies investigating salivary cortisol level as susceptibility
      marker for post-traumatic stress disorder (PTSD) produced inconsistent results.
      The aim of this study was to compare salivary cortisol concentration levels in
      PTSD patients with those in controls by synthesizing published data. METHODS: We
      did a systematic review, meta-analysis and meta-regression of studies comparing
      concentrations of salivary cortisol between patients with PTSD and controls. The
      electronic databases of PubMed, Embase, Web of Science and Psyc-ARTICLES were
      searched for relevant articles. A random-effects model with restricted maximum
      likelihood estimator is used to synthesize the effect size (assessed by
      standardized mean difference). RESULTS: A total of 784 articles were identified
      of which 22 were included in the final analysis. A trend of lower salivary
      cortisol levels was found in PTSD patients when compared with the controls (SMD =
      - 0.28, 95% CI-0.53;-0.04, p = 0.022). Subgroup analysis showed that the salivary
      cortisol levels were lower in patients with PTSD than in controls in studies
      conducted after 2007 or in studies using saliva samples collected in the morning.
      CONCLUSIONS: The evidence from this meta-analysis supports that salivary samples
      collected in the morning consistently showed a lower salivary cortisol level in
      patients with PTSD than in controls, although whether salivary cortisol could be
      used as a diagnostic tool requires further research.

PMID- 30290790
TI  - An enhanced regimen as post-exposure chemoprophylaxis for leprosy: PEP+.
AB  - The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow
      decline in leprosy incidence, forces us to be innovative and conduct cutting-edge
      research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for
      contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This
      is a promising new preventive measure that can be integrated into routine leprosy
      control programmes, as is being demonstrated in the Leprosy Post-Exposure
      Programme that is currently ongoing in eight countries.The limited (60%)
      effectiveness of SDR is likely due to the fact that some contacts have a
      preclinical infection beyond the early stages for which SDR is not sufficient to
      prevent the development of clinical signs and symptoms of leprosy. An enhanced
      regimen, more potent against a higher load of leprosy bacteria, would increase
      the effectiveness of this preventive measure significantly.The Netherlands
      Leprosy Relief (NLR) is developing a multi-country study aiming to show that
      breaking the chain of transmission of M. leprae is possible, evidenced by a
      dramatic reduction in incidence. In this study the assessment of the
      effectiveness of an enhanced prophylactic regimen for leprosy is an important
      component. To define the so called PEP++ regimen for this intervention study, NLR
      convened an Expert Meeting that was attended by clinical leprologists, public
      health experts, pharmacologists, dermatologists and microbiologists.The Expert
      Meeting advised on combinations of available drugs, with known efficacy against
      leprosy, as well as on the duration of the intake, aiming at a risk reduction of
      80-90%. To come to a conclusion the Expert Meeting considered the bactericidal,
      sterilising and bacteriostatic activity of the potential drugs. The criteria used
      to determine an optimal enhanced regimen were: effectiveness, safety,
      acceptability, availability, affordability, feasibility and not inducing drug
      resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++
      study should comprise three standard doses of rifampicin 600 mg (weight adjusted
      when given to children) plus moxifloxacin 400 mg given at four-weekly intervals.
      For children and for adults with contraindications for moxifloxacin, moxifloxacin
      should be replaced by clarithromycin 300 mg (weight adjusted).

PMID- 30290791
TI  - The palatine tonsil bacteriome, but not the mycobiome, is altered in HIV
      infection.
AB  - BACKGROUND: Microbial flora in several organs of HIV-infected individuals have
      been characterized; however, the palatine tonsil bacteriome and mycobiome and
      their relationship with each other remain unclear. Determining the palatine
      tonsil microbiome may provide a better understanding of the pathogenesis of oral
      and systemic complications in HIV-infected individuals. We conducted a cross
      sectional study to characterize the palatine tonsil microbiome in HIV-infected
      individuals. RESULTS: Palatine tonsillar swabs were collected from 46 HIV
      infected and 20 HIV-uninfected individuals. The bacteriome and mycobiome were
      analyzed by amplicon sequencing using Illumina MiSeq. The palatine tonsil
      bacteriome of the HIV-infected individuals differed from that of HIV-uninfected
      individuals in terms of the decreased relative abundances of the commensal genera
      Neisseria and Haemophilus. At the species level, the relative abundances and
      presence of Capnocytophaga ochracea, Neisseria cinerea, and Selenomonas noxia
      were higher in the HIV-infected group than those in the HIV-uninfected group. In
      contrast, fungal diversity and composition did not differ significantly between
      the two groups. Microbial intercorrelation analysis revealed that Candida and
      Neisseria were negatively correlated with each other in the HIV-infected group.
      HIV immune status did not influence the palatine tonsil microbiome in the HIV
      infected individuals. CONCLUSIONS: HIV-infected individuals exhibit dysbiotic
      changes in their palatine tonsil bacteriome, independent of immunological status.

PMID- 30290792
TI  - Transcriptional profiling of embryos lacking the lipoprotein receptor SR-B1
      reveals a regulatory circuit governing a neurodevelopmental or metabolic decision
      during neural tube closure.
AB  - BACKGROUND: The high-density lipoprotein receptor SR-B1 mediates cellular uptake
      of several lipid species, including cholesterol and vitamin E. During early mouse
      development, SR-B1 is located in the maternal-fetal interface, where it
      facilitates vitamin E transport towards the embryo. Consequently, mouse embryos
      lacking SR-B1 are vitamin E-deficient, and around half of them fail to close the
      neural tube and show cephalic neural tube defects (NTD). Here, we used
      transcriptomic profiling to identify the molecular determinants of this
      phenotypic difference between SR-B1 deficient embryos with normal morphology or
      with NTD. RESULTS: We used RNA-Seq to compare the transcriptomic profile of three
      groups of embryos retrieved from SR-B1 heterozygous intercrosses: wild-type E9.5
      embryos (WT), embryos lacking SR-B1 that are morphologically normal, without NTD
      (KO-N) and SR-B1 deficient embryos with this defect (KO-NTD). We identified over
      1000 differentially expressed genes: down-regulated genes in KO-NTD embryos were
      enriched for functions associated to neural development, while up-regulated genes
      in KO-NTD embryos were enriched for functions related to lipid metabolism.
      Feeding pregnant dams a vitamin E-enriched diet, which prevents NTD in SR-B1 KO
      embryos, resulted in mRNA levels for those differentially expressed genes that
      were more similar to KO-N than to KO-NTD embryos. We used gene regulatory network
      analysis to identify putative transcriptional regulators driving the different
      embryonic expression profiles, and identified a regulatory circuit controlled by
      the androgen receptor that may contribute to this dichotomous expression profile
      in SR-B1 embryos. Supporting this possibility, the expression level of the
      androgen receptor correlated strongly with the expression of several genes
      involved in neural development and lipid metabolism. CONCLUSIONS: Our analysis
      shows that normal and defective embryos lacking SR-B1 have divergent expression
      profiles, explained by a defined set of transcription factors that may explain
      their divergent phenotype. We propose that distinct expression profiles may be
      relevant during early development to support embryonic nutrition and neural tube
      closure.

PMID- 30290794
TI  - Determination of ED50 and time to effectiveness for intrathecal hydromorphone in
      laboring patients using Dixon's up-and-down sequential allocation method.
AB  - BACKGROUND: With the increasing occurrence of drug shortages, understanding the
      pharmacokinetics of alternative intrathecal opioid administration has gained
      importance. In particular, additional data are needed to comprehensively evaluate
      the analgesic properties of intrathecal hydromorphone in the laboring patient. In
      a phase 2 clinical trial, we set out to determine the median effective dose
      (ED50) and time to effectiveness for this drug in this population. METHODS: Using
      Dixon's up-and-down sequential allocation method, twenty women presenting for
      labor analgesia were prospectively enrolled. A combined spinal-epidural technique
      was used to deliver the determined dose of intrathecal hydromorphone. Visual
      analog pain scores were obtained assessing peak pain scores during serial uterine
      contractions. Effective pain relief was defined as achieving a pain score of less
      than or equal to 3 out of 10. The dose was deemed to be ineffective if the
      patient failed to achieve this level of relief after 30 min. RESULTS: The ED50 of
      hydromorphone in our population was 10.9 MUg (95% confidence interval 5.6-16.2
      MUg). Amongst patients for whom the dose was effective, the median time to pain
      relief was 24 min. One patient experienced both nausea and pruritus. No other
      complications were noted. CONCLUSION: Due to the prolonged time to onset,
      hydromorphone cannot be recommended in favor of substantively better alternatives
      such as sufentanil and fentanyl. TRIAL REGISTRATION: Clinicaltrials.gov
      registration number: NCT01598506.

PMID- 30290793
TI  - Integrated motivational interviewing and cognitive behaviour therapy for
      lifestyle mediators of overweight and obesity in community-dwelling adults: a
      systematic review and meta-analyses.
AB  - BACKGROUND: The aim of this study was to investigate whether integrated
      motivational interviewing and cognitive behaviour therapy leads to changes in
      lifestyle mediators of overweight and obesity in community-dwelling adults.
      METHOD: Six electronic databases were systematically searched up to 04 October,
      2017. Analyses were restricted to randomised controlled trials that examined the
      effect of integrated motivational interviewing and cognitive behaviour therapy on
      lifestyle mediators of overweight and obesity (physical activity, diet, body
      composition) in community-dwelling adults. Meta-analyses were conducted using
      change scores from baseline in outcome measures specific to the lifestyle
      mediators of overweight and obesity to determine standardized mean differences
      (SMD) and 95% confidence intervals (95% CI). The Grades of Recommendation,
      Assessment, Development and Evaluation approach was used to evaluate the quality
      of the evidence. RESULTS: Ten randomised controlled trials involving 1949
      participants were included. Results revealed moderate quality evidence that
      integrated motivational interviewing and cognitive behaviour therapy had a
      significant effect in increasing physical activity levels in community-dwelling
      adults (SMD: 0.18, 95% CI: 0.06 to 0.31, p < 0.05). The combined intervention
      resulted in a small, non-significant effect in body composition changes (SMD: 
      0.12, 95% CI: -0.24 to 0.01, p = 0.07). Insufficient evidence existed for outcome
      measures relating to dietary change. DISCUSSION: The addition of integrated
      motivational interviewing and cognitive behaviour therapy to usual care can lead
      to modest improvements in physical activity and body composition for community
      dwelling adults. The available evidence demonstrates that it is feasible to
      integrate MI with CBT and that this combined intervention has the potential to
      improve health-related outcomes. CONCLUSION: This review details recommendations
      for future research including the adoption of uniform objective outcome measures
      and well-defined interventions with sufficient follow-up durations and
      assessments of treatment fidelity.

PMID- 30290795
TI  - Rapid and efficient production of cecropin A antibacterial peptide in Escherichia
      coli by fusion with a self-aggregating protein.
AB  - BACKGROUND: Cecropin A (CeA), a natural cationic antimicrobial peptide, exerts
      potent antimicrobial activity against a broad spectrum of Gram-positive and Gram
      negative bacteria, making it an attractive candidate substitute for
      antimicrobials. However, the low production rate and cumbersome, expensive
      processes required for both its recombinant and chemical synthesis have seriously
      hindered the exploitation and application of CeA. Here, we utilized a short beta
      structured self-aggregating protein, ELK16, as a fusion partner of CeA, which
      allowed the efficient production of high-purity CeA antibacterial peptide with a
      simple inexpensive process. RESULTS: In this study, three different approaches to
      the production of CeA peptide were investigated: an affinity tag (His-tag)-fused
      protein expression system (AT-HIS system), a cell-free protein expression system
      (CF system), and a self-assembling peptide (ELK16)-fused protein expression
      system (SA-ELK16 system). In the AT-HIS and CF systems, the CeA peptide was
      obtained with purities of 92.1% and 90.4%, respectively, using one or more
      affinity-chromatographic purification steps. The procedures were tedious and
      costly, with CeA yields of only 0.41 and 0.93 MUg/mg wet cell weight,
      respectively. Surprisingly, in the SA-ELK16 system, about 6.2 MUg/mg wet cell
      weight of high-purity (approximately 99.8%) CeA peptide was obtained with a
      simple low-cost process including steps such as centrifugation and acetic acid
      treatment. An antimicrobial test showed that the high-purity CeA produced in this
      study had the same antimicrobial activity as synthetic CeA peptide. CONCLUSIONS:
      In this study, we designed a suitable expression system (SA-ELK16 system) for the
      production of the antibacterial peptide CeA and compared it with two other
      protein expression systems. A high yield of high-purity CeA peptide was obtained
      with the SA-ELK16 system, which greatly reduced the cost and time required for
      downstream processing. This system may provide a platform for the laboratory
      scale production of the CeA antibacterial peptide.

PMID- 30290796
TI  - Factors associated with anaemia in kidney transplant recipients in the first year
      after transplantation: a cross-sectional study.
AB  - BACKGROUND: Anaemia after kidney transplantation may reduce quality of life,
      graft or patient survival. We aimed to determine the prevalence and risk factors
      for anaemia in the initial 12 months after transplantation. METHODS: We conducted
      a cross-sectional study at 6 and 12 months after transplantation. Anaemia was
      defined by World Health Organization criteria taking into consideration
      erythropoietin use. Logistic regression was used to determine the association
      between demographic, clinical and pharmacological risk factors for the main
      outcome of moderate-severe anaemia. RESULTS: A total of 336 transplant recipients
      were included and the prevalence of moderate-severe anaemia was 27.4% at 6 months
      and 15.2% at 12 months. Lower kidney function, female gender, transferrin
      saturation below 10% and proteinuria were associated with moderate-severe anaemia
      at both time points. Recent intravenous immunoglobulin treatment was associated
      with anaemia at 6 months. Recent infection and acute rejection were also
      associated with anaemia 12 months. Around 20% of patients had at least one blood
      transfusion but they were uncommon beyond 3 months. CONCLUSIONS: Anaemia remains
      highly prevalent requiring treatment with erythropoietin and transfusions. Most
      identifiable risk factors relate to clinical problems rather than pharmacological
      management, while markers of iron-deficiency remain difficult to interpret in
      this setting.

PMID- 30290797
TI  - Reliability, ease of use and usefulness of I-MeDeSA for evaluating drug-drug
      interaction alerts in an Australian context.
AB  - BACKGROUND: Recently, attention has shifted to improving the design of
      computerized alerts via the incorporation of human factors design principles. The
      Instrument for Evaluating Human Factors Principles in Medication-Related Decision
      Support Alerts (I-MeDeSA) is a tool developed in the United States to guide
      improvements to alert design and facilitate selection of electronic systems with
      superior design. In this study, we aimed to determine the reliability, ease of
      use and usefulness of I-MeDeSA for assessing drug-drug interaction (DDI) alerts
      in an Australian context. METHODS: Using the I-MeDeSA, three reviewers
      independently evaluated DDI alert interfaces of seven electronic systems used in
      Australia. Inter-rater reliability was assessed and reviewers met to discuss
      difficulties in using I-MeDeSA and the tool's usefulness. RESULTS: Inter-rater
      reliability was high (Krippendorff's alpha = 0.76), however, ambiguous wording
      and the inclusion of conditional items impacted ease of use. A number of items
      were not relevant to Australian implementations and as a result, most systems
      achieved an I-MeDeSA score of less than 50%. CONCLUSIONS: The I-MeDeSA proved to
      be reliable, but item wording and structure made application difficult. Future
      studies should investigate potential modifications to the I-MeDeSA to improve
      ease of use and increase applicability to a variety of system configurations.

PMID- 30290798
TI  - Caesarean section rate and postnatal bed occupancy: a retrospective study
      replacing assumptions with evidence.
AB  - BACKGROUND: Obstetric units across the UK face resource pressures alongside a
      rising rate of Caesarean section (CS). It is assumed that this places a further
      burden in the form of postnatal bed demands. The number of inpatient beds has
      fallen nationally, and this may be used to justify attempts to restrict the CS
      rate. We set out to replace such assumptions with evidence. We did not find any
      similar contemporary analysis in a literature search. METHODS: The postnatal
      length of stay (LOS) of women delivering at Watford General Hospital, a large
      unit hosting around 5500 deliveries per annum, was stratified by mode of
      delivery. Differences within and across time periods were analysed. RESULTS: The
      CS rate rose from 14.5% in 1995 to 30.9% in 2015. The mean LOS post-CS declined
      from 4.2 to 2.4 days. These data were statistically significant to p < 0.001.
      Over this period the standardised total postnatal bed use for all delivery modes
      fell from 11083 days to 7894 days. A 113% rise in the CS rate was accommodated by
      only a 19.8% rise in postnatal bed use attributable to CS patients. CONCLUSIONS:
      Whatever pressures may be exacerbated by the rising CS rate, bed occupancy is not
      one of them. In discussion we widen our argument to suggest that resource
      pressures should not be used to justify limitations in the CS rate.

PMID- 30290799
TI  - Shady business: understanding the spatial ecology of exophilic Anopheles
      mosquitoes.
AB  - BACKGROUND: Understanding the ecology of exophilic anophelines is a key step
      toward developing outdoor control strategies to complement existing indoor
      control tools against malaria vectors. This study was conducted to assess the
      movement pattern of exophilic Anopheles mosquitoes between blood meal sources and
      resting habitats, and the landscape factors dictating their resting habitat
      choice. RESULTS: Resting clay pots were placed at 5 m, 25 m, 50 m, 75 m and 100 m
      away from isolated focal houses, radiating from them in four directions. The
      locations of the clay pots represent heterogeneous land cover types at a
      relatively fine spatial scale in the landscape. The effect of the landscape
      characters on the number of both female and male anophelines caught was modelled
      using zero-inflated negative binomial regression with a log link function. A
      total of 420 Anopheles mosquitoes (353 females and 67 males) belonging to three
      species; Anopheles arabiensis, Anopheles pharoensis, and Anopheles tenebrosus
      were caught in the resting clay pots, with An. arabiensis being the dominant
      species. Canopy cover, distance from the house, and land cover type were the
      significant landscape characters influencing the aggregation of resting
      mosquitoes. Both the count and binary models showed that canopy cover was the
      strongest predictor variable on the counts and the presence of Anopheles
      mosquitoes in the clay pots. Female Anopheles were most frequently found resting
      in the pots placed in banana plantations, and at sampling points that were at the
      greater distances (75 m and 100 m) from the focal house. CONCLUSIONS: This study
      showed that exophilic Anopheles mosquitoes tend to rest in shaded areas some
      distance away from human habitation. These findings are important when targeting
      mosquitoes outdoors, complementing the existing effort being made to control
      malaria vectors indoors.

PMID- 30290800
TI  - Comparative cardio and developmental toxicity induced by the popular medicinal
      extract of Sutherlandia frutescens (L.) R.Br. detected using a zebrafish
      Tuebingen embryo model.
AB  - BACKGROUND: Sutherlandia frutescens is one of the most promising commercialized,
      indigenous and medicinal plants of South Africa that is used as an immune
      booster, and a traditional treatment for cancer. However, few studies report on
      its toxicology and dosage in vivo. There is still room to better understand its
      cytotoxicity effects in animal systems. METHODS: We prepared two extracts, one
      with 80% (v/v) ethanol, and the other, with water. Both were studied to determine
      the maximum tolerable concentration when extracts were applied at 0 to 200 MUg/ml
      to a Tuebingen zebrafish embryo line. The development of zebrafish embryos after
      24 h post fertilization (hpf) was studied. A concentration range of 5 MUg/ml to
      50 MUg/ml was then chosen to monitor the ontological development of cultured
      embryos. A liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS)
      method was used to study the differences of the two experimental extracts.
      Chemical variation between the extracts was illustrated using chemometrics.
      RESULTS: Both extracts led to bleeding and pericardial cyst formation when
      applied at high concentrations to the zebrafish embryo culture. Chronic
      teratogenic toxicities, leading to pericardial edema, yolk sac swelling, and
      other abnormal developmental characteristics, were detected. The aqueous extracts
      of S. frutescens were less toxic to the larvae than the ethanol extracts,
      validating preference for aqueous preparations when used in traditional medicine.
      Chemical differences between the water extracts and alcoholic extracts were
      analysed using LC-MS/MS. A supervised metabolomics approach, targeting the
      sutherlandiosides and sutherlandins using orthogonal partial least squares
      discriminant analysis (OPLS-DA), illustrated that sutherlandiosides were the main
      chemical features that can be used to distinguish between the two extracts,
      despite the extracts being highly similar in their chemical constituents.
      CONCLUSION: The water extract caused less cytotoxic and abnormal developmental
      effects compared to the ethanolic extract, and, this is likely due to differences
      in concentrations of extracted chemicals rather than the chemical profile per se.
      This study provides more evidence of cytotoxicity effects linked to S. frutescens
      using the zebrafish embryo bioassay as a study tool.

PMID- 30290801
TI  - Concomitant inhaled corticosteroid use and the risk of pneumonia in COPD: a
      matched-subgroup post hoc analysis of the UPLIFT(r) trial.
AB  - BACKGROUND: Use of inhaled corticosteroids (ICS) increases the risk of pneumonia
      in chronic obstructive pulmonary disease (COPD), but the magnitude of risk with
      different ICS remains unclear. METHODS: A post hoc analysis of the 4-year
      UPLIFT(r) trial to assess whether pneumonia risk differed by type of ICS
      (fluticasone propionate [FP], other ICS, or no ICS) in permanent users (defined
      by use until end of study) or in users at baseline (sensitivity analysis).
      RESULTS: For the permanent-users analysis, 825 patients receiving FP throughout
      the trial, 825 patients receiving other ICS and 825 patients not receiving ICS
      were matched on relevant baseline features 1:1:1. A significantly greater risk of
      pneumonia was observed for FP versus no ICS: the hazard ratio (HR) for risk of
      pneumonia was 1.33 (95% confidence interval [CI] 1.00, 1.75; p = 0.046) and the
      rate ratio (RR) was 1.58 (95% CI 1.05, 2.37; p = 0.028). A greater risk was also
      found for FP versus other ICS: HR 1.28 (95% CI 0.97, 1.68; p = 0.078) and RR 1.48
      (95% CI 1.00, 2.19; p = 0.049). A higher proportion of patients on FP were
      hospitalized with pneumonia (7.9%) versus other ICS (6.7%) or no ICS (5.9%).
      Whilst other ICS use was associated with the highest number of fatal pneumonia
      events, the total number of fatal pneumonia incidents was low. A similar pattern
      was observed in the sensitivity analyses, which included 4002 patients on
      different treatments at baseline (FP, other ICS, and no ICS) and considered
      potential switches during the study. CONCLUSION: The results support existing
      evidence of an increased pneumonia risk with FP use compared with other ICS and
      no ICS use in patients with COPD. Healthcare professionals should evaluate the
      risk-benefit ratio of using ICS when making treatment decisions with their
      patients. TRIAL REGISTRATION: Post hoc analysis of UPLIFT(r). ClinicalTrials.gov
      number: NCT00144339 . Retrospectively registered September 2, 2005.

PMID- 30290802
TI  - An odorant receptor from Anopheles sinensis in China is sensitive to oviposition
      attractants.
AB  - BACKGROUND: Anopheles sinensis is an important vector for the spread of malaria
      in China. Olfactory-related behaviours, particularly oviposition site seeking,
      offer opportunities for disrupting the disease-transmission process. RESULTS:
      This is the first report of the identification and characterization of AsinOrco
      and AsinOR10 in An. sinensis. AsinOrco and AsinOR10 share 97.49% and 90.37% amino
      acid sequence identity, respectively, with related sequences in Anopheles
      gambiae. A functional analysis demonstrated that AsinOrco- and AsinOR10
      coexpressing HEK293 cells were highly sensitive to 3-methylindole, but showed no
      significant differences in response to other test odorants when compared to DMSO.
      CONCLUSIONS: AsinOrco was characterized as a new member of the Orco ortholog
      subfamily. AsinOR10, which appears to be a member of the OR2-10 subfamily, is
      directly involved in identification of oviposition sites. This finding will help
      to elucidate the molecular mechanisms underlying olfactory signaling in An.
      sinensis and provide many more molecular targets for eco-friendly pest control.

PMID- 30290803
TI  - The randomised uterine septum transsection trial (TRUST): design and protocol.
AB  - BACKGROUND: A septate uterus is a uterine anomaly that may affect reproductive
      outcome, and is associated with an increased risk for miscarriage, subfertility
      and preterm birth. Resection of the septum is subject of debate. There is no
      convincing evidence concerning its effectiveness and safety. This study aims to
      assess whether hysteroscopic septum resection improves reproductive outcome in
      women with a septate uterus. METHODS/DESIGN: A multi-centre randomised controlled
      trial comparing hysteroscopic septum resection and expectant management in women
      with recurrent miscarriage or subfertility and diagnosed with a septate uterus.
      The primary outcome is live birth, defined as the birth of a living foetus beyond
      24 weeks of gestational age. Secondary outcomes are ongoing pregnancy, clinical
      pregnancy, miscarriage and complications following hysteroscopic septum
      resection. The analysis will be performed according to the intention to treat
      principle. Kaplan-Meier curves will be constructed, estimating the cumulative
      probability of conception leading to live birth rate over time. Based on
      retrospective studies, we anticipate an improvement of the live birth rate from
      35% without surgery to 70% with surgery. To demonstrate this difference, 68 women
      need to be randomised. DISCUSSION: Hysteroscopic septum resection is worldwide
      considered as a standard procedure in women with a septate uterus. Solid evidence
      for this recommendation is lacking and data from randomised trials is urgently
      needed. TRIAL REGISTRATION: Dutch trial registry ( NTR1676 , 18th of February
      2009).

PMID- 30290804
TI  - Genetic diagnosis of neurofibromatosis type 1: targeted next- generation
      sequencing with Multiple Ligation-Dependent Probe Amplification analysis.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is a dominantly inherited tumor
      predisposition syndrome that targets the peripheral nervous system. It is caused
      by mutations of the NF1 gene which serve as a negative regulator of the cellular
      Ras/MAPK (mitogen-activated protein kinases) signaling pathway. Owing to the
      complexity in some parts of clinical diagnoses and the need for better
      understanding of its molecular relationships, a genetic characterization of this
      disorder will be helpful in the clinical setting. METHODS: In this study, we
      present a customized targeted gene panel of NF1/KRAS/BRAF/p53 and SPRED1 genes
      combined with Multiple Ligation-Dependent Probe Amplification analysis for the
      NF1 mutation screening in a cohort of patients clinically suspected as NF1.
      RESULTS: In this study, we identified 73 NF1 mutations and two BRAF novel
      variants from 100 NF1 patients who were suspected as having NF1. These genetic
      alterations are heterogeneous and distribute in a complicated way without
      clustering in either cysteine-serine-rich domain or within the GAP-related
      domain. We also detected fifteen multi-exon deletions within the NF1 gene by MLPA
      Analysis. CONCLUSIONS: Our results suggested that a genetic screening using a NGS
      panel with high coverage of Ras-signaling components combined with Multiple
      Ligation-Dependent Probe Amplification analysis will enable differential
      diagnosis of patients with overlapping clinical features.

PMID- 30290806
TI  - Dissociating motor learning from recovery in exoskeleton training post-stroke.
AB  - BACKGROUND: A large number of robotic or gravity-supporting devices have been
      developed for rehabilitation of upper extremity post-stroke. Because these
      devices continuously monitor performance data during training, they could
      potentially help to develop predictive models of the effects of motor training on
      recovery. However, during training with such devices, patients must become adept
      at using the new "tool" of the exoskeleton, including learning the new forces and
      visuomotor transformations associated with the device. We thus hypothesized that
      the changes in performance during extensive training with a passive, gravity
      supporting, exoskeleton device (the Armeo Spring) will follow an initial fast
      phase, due to learning to use the device, and a slower phase that corresponds to
      reduction in overall arm impairment. Of interest was whether these fast and slow
      processes were related. METHODS: To test the two-process hypothesis, we used
      mixed-effect exponential models to identify putative fast and slow changes in
      smoothness of arm movements during 80 arm reaching tests performed during 20 days
      of exoskeleton training in 53 individuals with post-acute stroke. RESULTS: In
      line with our hypothesis, we found that double exponential models better fit the
      changes in smoothness of arm movements than single exponential models. In
      contrast, single exponential models better fit the data for a group of young
      healthy control subjects. In addition, in the stroke group, we showed that
      smoothness correlated with a measure of impairment (the upper extremity Fugl
      Meyer score - UEFM) at the end, but not at the beginning, of training.
      Furthermore, the improvement in movement smoothness due to the slow component,
      but not to the fast component, strongly correlated with the improvement in the
      UEFM between the beginning and end of training. There was no correlation between
      the change of peaks due to the fast process and the changes due to the slow
      process. Finally, the improvement in smoothness due to the slow, but not the
      fast, component correlated with the number of days since stroke at the onset of
      training - i.e. participants who started exoskeleton training sooner after stroke
      improved their smoothness more. CONCLUSIONS: Our results therefore demonstrate
      that at least two processes are involved in in performance improvements measured
      during mechanized training post-stroke. The fast process is consistent with
      learning to use the exoskeleton, while the slow process independently reflects
      the reduction in upper extremity impairment.

PMID- 30290807
TI  - Equity assessment of the distribution of CT and MRI scanners in China: a panel
      data analysis.
AB  - BACKGROUND: Distribution equity assessment of computed tomography (CT) and
      magnetic resonance imaging (MRI) scanners is an important dimension of access to
      health technology. However, limited studies on the subject have been done in
      China. This study aims to reveal the distribution status of CT and MRI scanners
      and assess their distribution equity of them in China. METHODS: Five provinces
      with 66 cities from China were selected as the study sites. Descriptive analysis
      was used for the absolute number and number per million population of CT and MRI
      scanners in the study sites. Fixed effect model was used to examine the health
      service factors that were associated with the allocation of CT and MRI scanners.
      The Gini coefficient and concentration index was used to evaluate the
      distribution equity of CT and MRI scanners. RESULTS: The absolute number and
      number per million population of CT and MRI scanners in five provinces were lower
      than those of Organization for Economic Co-operation and Development (OECD)
      countries, but annual growth rates were relatively higher from 2005 or 2006 to
      2013. Population, GDP, number of hospitals, number of health professionals,
      number of hospital beds, number of outpatient visits, and number of inpatient
      visits all had a positive correlation with the allocation number of CT and MRI
      scanners. Moreover, the number of health professionals and the number of beds had
      a much closer correlation than other variables. All the Gini coefficients of CT
      and MRI had decreased overall. The concentration indices of CT and MRI were all
      positive and no more than 0.30. CONCLUSIONS: Large gaps in the number of CT and
      MRI scanners per million population between China and OECD countries emerge,
      although the growth rate is higher in China. The distribution equity of CT and
      MRI scanners in China was relatively good from 2005 or 2006 to 2013. The overall
      distribution equity of CT and MRI scanners also improved during the period.
      However, consideration attention should be given to the area with large economic
      disparities.

PMID- 30290805
TI  - Biotechnological applications of archaeal enzymes from extreme environments.
AB  - To date, many industrial processes are performed using chemical compounds, which
      are harmful to nature. An alternative to overcome this problem is biocatalysis,
      which uses whole cells or enzymes to carry out chemical reactions in an
      environmentally friendly manner. Enzymes can be used as biocatalyst in food and
      feed, pharmaceutical, textile, detergent and beverage industries, among others.
      Since industrial processes require harsh reaction conditions to be performed,
      these enzymes must possess several characteristics that make them suitable for
      this purpose. Currently the best option is to use enzymes from extremophilic
      microorganisms, particularly archaea because of their special characteristics,
      such as stability to elevated temperatures, extremes of pH, organic solvents, and
      high ionic strength. Extremozymes, are being used in biotechnological industry
      and improved through modern technologies, such as protein engineering for best
      performance. Despite the wide distribution of archaea, exist only few reports
      about these microorganisms isolated from Antarctica and very little is known
      about thermophilic or hyperthermophilic archaeal enzymes particularly from
      Antarctica. This review summarizes current knowledge of archaeal enzymes with
      biotechnological applications, including two extremozymes from Antarctic archaea
      with potential industrial use, which are being studied in our laboratory. Both
      enzymes have been discovered through conventional screening and genome
      sequencing, respectively.

PMID- 30290808
TI  - A randomized trial of dihydroartemisinin-piperaquine versus artemether
      lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in
      Mali.
AB  - BACKGROUND: Artemether-lumefantrine (AL) and artesunate-amodiaquine are first
      line treatment for uncomplicated malaria in many endemic countries, including
      Mali. Dihydroartemisinin-piperaquine (DHA-PQ) is also an alternative first-line
      artemisinin-based combination therapy, but only few data are available on DHA-PQ
      efficacy in sub-Saharan Africa. The main aim of this study was to compare
      clinical efficacy of DHA-PQ versus AL, using the World Health Organization (WHO)
      42-day in vivo protocol. METHODS: The efficacy of three-dose regimens of DHA-PQ
      was compared to AL combination in a randomized, comparative open label trial
      using the WHO 42-day follow-up protocol from 2013 to 2015 in Doneguebougou and
      Torodo, Mali. The primary endpoint was to access the PCR-corrected Adequate
      Clinical and Parasitological Responses at day 28. RESULTS: A total of 317
      uncomplicated malaria patients were enrolled, with 159 in DHA-PQ arm and 158 in
      AL arm. The parasite positivity rate decreased from 68.4% (95% CI 60.5-75.5) on
      day 1 to 3.8% (95% CI 1.4-8.1) on day 2 for DHA-PQ and 79.8% (95% CI 72.3-85.7)
      on day 1 to 9.5% (95% CI 5.4-15.2) on day 2 for AL, (p = 0.04). There was a
      significant difference in the uncorrected ACPR between DHA-PQ and AL, both at 28
      day and 42-day follow-up with 97.4% (95% CI 93.5-99.3) in DHA-PQ vs 84.5% (95% CI
      77.8-89.8) in AL (p < 0.001) and 94.2% (95% CI 89.3-97.3) in DHA-PQ vs 73.4% (95%
      CI 65.7-80.2) in AL, respectively (p < 0.001). After molecular correction, there
      was no significant difference in ACPRc between DHA-PQ and AL, both at the 28-day
      and 42-day follow-up with 99.4% (95% CI 96.5-100) in DHA-PQ versus 98.1% (95% CI
      94.5-99.6) in AL (p = 0.3) and 99.3% (95% CI 96.5-100) in DHA-PQ vs 97.4% (95% CI
      93.5-99.3) in AL (p = 0.2). There was no significant difference between DHA-PQ
      and AL in QTc prolongation 12.1% vs 7%, respectively (p = 0.4). CONCLUSION: The
      results showed that dihydroartemisinin-piperaquine and artemether-lumefantrine
      were clinically efficacious on Plasmodium falciparum parasites in Mali.

PMID- 30290809
TI  - Antiestrogen- and tamoxifen-induced effects on calcium-activated chloride
      currents in epithelial cells carrying the ?F508-CFTR point mutation.
AB  - BACKGROUND: Although pharmacological treatment has increased the average life
      expectancy of patients with cystic fibrosis, the median survival of females is
      shorter than that of males. In vitro and in vivo studies have shown that
      estrogens play a relevant role in the disease progression. The aim of this study
      was to investigate the effects of 17beta-estradiol and tamoxifen citrate (TMX) on
      calcium-activated chloride channel (CaCC) currents in human bronchial epithelial
      cells carrying the DeltaPhe508-CFTR mutation both in homozygosis and in
      heterozygosis. METHODS: Perforated patch clamp experiments were performed on
      single cells of the immortalized cell lines CFBE and IB3-1. Gramicidin (10 or 20
      MUM) was added to the electrode solution to reach the whole cell configuration.
      The electrical stimulation protocol consisted of square voltages ranging from -
      80 to + 80 mV, in steps of 20 mV and with a duration of 800 msec. RESULTS: The
      presence of 17beta-estradiol significantly reduced the CaCC currents, both in
      basal conditions and in the presence of ATP (100 MUM). The addition of TMX (10
      MUM) completely restored the currents abolished by 17beta-estradiol, in basal
      conditions and after stimulation with ATP in both CFBE and IB3-1 cells. TMX had a
      strong, direct action on membrane current density, which significantly increased
      more than 4-fold in both cases. The membrane current stimulation produced by TMX
      was further enhanced by the addition of ATP. CFBE cells incubated for 24 h with 3
      MUM VX-809 (a CFTR corrector) and then acutely stimulated with VX-770 (a CFTR
      potentiator) in the presence of forskolin, showed an increase of chloride
      currents which were abolished by Inh-172. The chloride current density induced by
      TMX + ATP was, on average, greater than that obtained with VX-809 + VX-770 +
      forskolin. The currents elicited by TMX + ATP were abolished by the addition of
      NPPB, a CaCC inhibitor. The combined administration of TMX/ATP and VXs/FSK had an
      additional effect on chloride currents. CONCLUSIONS: Our results show that TMX
      restores CaCC currents inhibited by 17beta-estradiol and directly activates the
      transmembrane chloride currents potentiated by ATP, an effect which is mutation
      independent. The combined effect of TMX with current used treatments for cystic
      fibrosis could be of benefit to patients.

PMID- 30290810
TI  - Association of serum high-density lipoprotein cholesterol with microalbuminuria
      in type 2 diabetes patients.
AB  - BACKGROUND: The association of serum high-density lipoprotein cholesterol (HDL-C)
      with microalbuminuria in type 2 diabetes mellitus (T2DM) remains controversial.
      Therefore, a cross-sectional study was conducted on patients with T2DM to
      investigate the relationship of HDL-C with microalbuminuria. METHODS: A total of
      524 participants with T2DM were recruited in this cross-sectional study. The
      patients were divided into four groups according to serum HDL-C quartile. A
      nonparametric test was employed to assess the relationships across quartiles with
      clinical parameters and demographics. Multivariate logistic regression analysis
      was further performed. RESULTS: Of the 524 patients, 138 (26.3%) were found to
      have microalbuminuria by urinary albumin excretion rate determination. Serum HDL
      C levels in microalbuminuria group were significantly lower than those in non
      microalbuminuria group (1.04 (0.90-1.21) vs. 1.10 (0.94-1.31) mmol/L, P = 0.002).
      The nonparametric test for trend showed that the prevalence of microalbuminuria
      was significantly reduced for subjects of the fourth quartile of HDL-C compared
      to the first to third quartile (13.5% vs. 33.1%, 28.6%, 29.4%, P = 0.001).
      Multivariate logistic regression showed that subjects within the highest quartile
      of HDL-C had lower odds of microalbuminuria than those within the lowest quartile
      of HDL-C (OR = 0.17, 95% CI 0.15-0.52, P = 0.004). CONCLUSIONS: Higher levels of
      serum HDL-C were associated with decreased rates of microalbuminuria in T2DM
      patients.

PMID- 30290812
TI  - Health and sustainable development; strengthening peri-operative care in low
      income countries to improve maternal and neonatal outcomes.
AB  - BACKGROUND: Uganda is far from meeting the sustainable development goals on
      maternal and neonatal mortality with a maternal mortality ratio of 383/100,000
      live births, and 33% of the women gave birth by 18 years. The neonatal mortality
      ratio was 29/1000 live births and 96 stillbirths occur every day due to placental
      abruption, and/or eclampsia - preeclampsia and other unkown causes. These deaths
      could be reduced with access to timely safe surgery and safe anaesthesia if the
      Comprehensive Emergency Obstetric and Newborn Care services (CEmONC), and
      appropriate intensive care post operatively were implemented. A 2013 multi
      national survey by Epiu et al. showed that, the Safe Surgical Checklist was not
      available for use at main referral hospitals in East Africa. We, therefore, set
      out to further assess 64 government and private hospitals in Uganda for the
      availability and usage of the WHO Checklists, and investigate the post-operative
      care of paturients; to advocate for CEmONC implementation in similarly burdened
      low income countries. METHODS: The cross-sectional survey was conducted at 64
      government and private hospitals in Uganda using preset questionnaires. RESULTS:
      We surveyed 41% of all hospitals in Uganda: 100% of the government regional
      referral hospitals, 16% of government district hospitals and 33% of all private
      hospitals. Only 22/64 (34.38%: 95% CI = 23.56-47.09) used the WHO Safe Surgical
      Checklist. Additionally, only 6% of the government hospitals and 14% not-for
      profit hospitals had access to Intensive Care Unit (ICU) services for
      postoperative care compared to 57% of the private hospitals. CONCLUSIONS: There
      is urgent need to make WHO checklists available and operationalized.
      Strengthening peri-operative care in obstetrics would decrease maternal and
      neonatal morbidity and move closer to the goal of safe motherhood working towards
      Universal Health Care.

PMID- 30290811
TI  - A new ALK isoform transported by extracellular vesicles confers drug resistance
      to melanoma cells.
AB  - BACKGROUND: Drug resistance remains an unsolved clinical issue in oncology.
      Despite promising initial responses obtained with BRAF and MEK kinase inhibitors,
      resistance to treatment develops within months in virtually all melanoma
      patients. METHODS: Microarray analyses were performed in BRAF inhibitor-sensitive
      and resistant cell lines to identify changes in the transcriptome that might play
      a role in resistance. siRNA approaches and kinase inhibitors were used to assess
      the involvement of the identified Anaplastic Lymphoma Kinase (ALK) in drug
      resistance. The capability of extracellular vesicles (EVs) to transfer drug
      resistant properties was investigated in co-culture assays. RESULTS: Here, we
      report a new mechanism of acquired drug resistance involving the activation of a
      novel truncated form of ALK. Knock down or inhibition of ALK re-sensitised
      resistant cells to BRAF inhibition and induced apoptosis. Interestingly,
      truncated ALK was also secreted into EVs and we show that EVs were the vehicle
      for transferring drug resistance. CONCLUSIONS: To our knowledge, this is the
      first report demonstrating the functional involvement of EVs in melanoma drug
      resistance by transporting a truncated but functional form of ALK, able to
      activate the MAPK signalling pathway in target cells. Combined inhibition of ALK
      and BRAF dramatically reduced tumour growth in vivo. These findings make ALK a
      promising clinical target in melanoma patients.

PMID- 30290814
TI  - Numerical simulation of embryo transfer: how the viscosity of transferred medium
      affects the transport of embryos.
AB  - BACKGROUND: Embryo transfer (ET) is a key step of assisted reproductive
      procedures, where the transferred medium containing the embryos is injected into
      the uterine cavity through a transcervical catheter and blended with intrauterine
      fluid in the uterine cavity. This procedure determines the delivery sites of
      embryos in the uterine cavity and has crucial impact on the implantation. Due to
      practical restrictions and ethical issues, it is often difficult to perform an in
      vivo study in humans to examine factors that affect the motions and delivery of
      embryos during ET. Alternatively, mathematical modeling is a powerful tool to
      that end. RESULTS: A computational model is developed to simulate the
      intrauterine mixing flow and track the embryo motions. Two important factors
      affecting the intrauterine flow are studied via this model: the viscosity of the
      transferred medium and the injection speed. Numerical results show that the
      dispersion pattern and the final delivery sites of the embryos are significantly
      influenced by the viscosity of the transferred medium. Specially, increasing the
      transferred medium viscosity close to that of the uterine fluid can enhance the
      probability that the embryos are delivered close to the fundus and keep them from
      being dragged backward to the cervix during catheter withdrawal. In addition, a
      slow injection speed can lower the driving force on the embryo during ET, which
      can prevent the embryo from being injured. CONCLUSIONS: Based on our study, the
      practice of using a transferred medium with similar viscosity to that of the
      uterine fluid and a slow injection speed is recommended for real embryo transfer
      procedures in clinic.

PMID- 30290813
TI  - Does it take three to tango? An unsuspected multimorbidity of CD8+ T cell
      lymphoproliferative disorder, malaria, and EBV infection.
AB  - BACKGROUND: Malaria is known to cause acute and deadly complications. However,
      malaria can cause unforeseen pathologies due to its chronicity. It increases the
      risk of endemic Burkitt Lymphoma development by inducing DNA damage in germinal
      centre (GC) B cells, and leading higher frequency of Epstein-Barr virus (EBV)
      infected cells in GCs. EBV is well known for its tropism for B cells. However,
      less is known about EBV's interaction with T cells and its association with T
      cell lymphoma. CASE PRESENTATION: A 43-year-old Sudanese male admitted to
      hospital in Istanbul, Turkey, a non-endemic country, with hyperpigmented painful
      skin rashes on his whole body. A complete blood count and a peripheral blood
      smear during admission revealed large granular lymphocytes (LGLs) with abnormally
      higher CD8 T cell numbers. Additional skin biopsy and pathology results were
      compatible with CD8+ T cell lymphoproliferative disorder with skin involvement.
      Patient was treated and discharged. However, a pathologist noticed unusual
      structures in skin tissue samples. Careful evaluation of skin biopsy samples by
      polarized microscopy revealed birefringent crystalloid structures resembling
      malarial haemozoin mainly loaded in macrophages and giant histiocytes. After
      purification of DNA from the skin biopsy samples, nested PCR was performed for
      the detection of Plasmodium parasites and Plasmodium falciparum DNA was
      amplified. Because, the co-presence of EBV infection with malaria is a well-known
      aetiology of lymphoma, EBV-early RNA (EBER) transcripts were investigated in
      paraffin-embedded tissue samples and found to be positive in macrophage-like
      histiocytes. CONCLUSIONS: This is a unique case of malaria and EBV infection in a
      T-LGL lymphoma patient who presented in a non-endemic country. This case
      emphasizes the clinical importance of EBV monitoring in T-LGL patients with skin
      involvement. Notably, Plasmodium infection should be examined in patients from
      malaria endemic regions by pathological and molecular investigations.

PMID- 30290816
TI  - Dietary patterns of university students in the UK: a cross-sectional study.
AB  - BACKGROUND: University represents a key transition into adulthood for many
      adolescents but there are associated concerns about health and behaviours. One
      important aspect relates to diet and there is emerging evidence that university
      students may consume poor quality diets, with potential implications for body
      weight and long-term health. This research aimed to characterise dietary patterns
      of university students in the UK and their sociodemographic and lifestyle
      antecedents. METHODS: An online, cross-sectional survey was undertaken with a
      convenience sample of 1448 university students from five UK universities (King's
      College London, Universities of St Andrews, Southampton and Sheffield, and Ulster
      University). The survey comprised a validated food frequency questionnaire
      alongside lifestyle and sociodemographic questions. Dietary patterns were
      generated from food frequency intake data using principal components analysis.
      Nutrient intakes were estimated to characterise the nutrient profile of each
      dietary pattern. Associations with sociodemographic variables were assessed
      through general linear modelling. RESULTS: Dietary analyses revealed four major
      dietary patterns: 'vegetarian'; 'snacking'; 'health-conscious'; and 'convenience,
      red meat & alcohol'. The 'health-conscious' pattern had the most favourable
      micronutrient profile. Students' gender, age, year of study, geographical
      location and cooking ability were associated with differences in pattern
      behaviour. Female students favoured the 'vegetarian' pattern, whilst male
      students preferred the 'convenience, red meat & alcohol' pattern. Less healthful
      dietary patterns were positively associated with lifestyle risk factors such as
      smoking, low physical activity and take-away consumption. The health-conscious
      pattern had greatest nutrient density. The 'convenience, red meat & alcohol'
      pattern was associated with higher weekly food spending; this pattern was also
      identified most consistently across universities. Students reporting greater
      cooking ability tended towards the 'vegetarian' and 'health-conscious' patterns.
      CONCLUSIONS: Food intake varied amongst university students. A substantial
      proportion of students followed health-promoting diets, which had good nutrient
      profiles obviating a need for dietary intervention. However, some students
      consumed poor diets, incurred greater food costs and practised unfavourable
      lifestyle behaviours, which may have long-term health effects. University policy
      to improve students' diets should incorporate efforts to promote student
      engagement in cooking and food preparation, and increased availability of low
      cost healthier food items.

PMID- 30290815
TI  - malariaAtlas: an R interface to global malariometric data hosted by the Malaria
      Atlas Project.
AB  - BACKGROUND: The Malaria Atlas Project (MAP) has worked to assemble and maintain a
      global open-access database of spatial malariometric data for over a decade. This
      data spans various formats and topics, including: geo-located surveys of malaria
      parasite rate; global administrative boundary shapefiles; and global and regional
      rasters representing the distribution of malaria and associated illnesses, blood
      disorders, and intervention coverage. MAP has recently released malariaAtlas, an
      R package providing a direct interface to MAP's routinely-updated malariometric
      databases and research outputs. METHODS AND RESULTS: The current paper reviews
      the functionality available in malariaAtlas and highlights its utility for
      spatial epidemiological analysis of malaria. malariaAtlas enables users to freely
      download, visualise and analyse global malariometric data within R. Currently
      available data types include: malaria parasite rate and vector occurrence point
      data; subnational administrative boundary shapefiles; and a large suite of
      rasters covering a diverse range of metrics related to malaria research.
      malariaAtlas is here used in two mock analyses to illustrate how this data may be
      incorporated into a standard R workflow for spatial analysis. CONCLUSIONS:
      malariaAtlas is the first open-access R-interface to malariometric data,
      providing a new and reproducible means of accessing such data within a freely
      available and commonly used statistical software environment. In this way, the
      malariaAtlas package aims to contribute to the environment of data-sharing within
      the malaria research community.

PMID- 30290817
TI  - Elevated serum soluble programmed cell death ligand 1 concentration as a
      potential marker for poor prognosis in small cell lung cancer patients with
      chemotherapy.
AB  - BACKGROUND: Potential relationship between serum soluble programmed cell death
      ligand 1 and prognosis of small cell lung cancer is not well explored. The aim of
      the study was to reveal the prognostic significance of serum soluble programmed
      cell death ligand 1 in patients with small cell lung cancer. METHODS: A total of
      250 small cell lung cancer patients and 250 controls were included. Research
      information was obtained from their medical records. Blood samples were collected
      on admission. Serum concentration of programmed cell death ligand 1 was measured
      using Enzyme-Linked Immunosorbent Assay. The patients underwent cisplatin
      etoposide chemotherapy with a maximum of six cycles. Subsequently, they were
      followed-up for 12 months, and therapeutic response and cancer death were
      recorded. RESULTS: Serum concentration of programmed cell death ligand 1 was
      higher in the patients than in the controls on admission (P < 0.001). After
      chemotherapy, 112 patients had no response to this therapy. In the 12-month
      follow up period, 118 patients died due to this cancer. Multivariate Cox
      regression model revealed that the higher serum concentration of programmed cell
      death ligand 1 on admission was associated with the higher risk of no response to
      chemotherapy or cancer caused death (HR: 1.40, 95% CI: 1.05 ~ 1.87; HR: 1.43, 95%
      CI: 1.08 ~ 1.87). CONCLUSION: Elevated serum concentration of soluble programmed
      cell death ligand 1 might be an independent risk factor for non-response to
      chemotherapy and cancer caused death in small cell lung cancer patients.

PMID- 30290818
TI  - End-of-life situations in cardiology: a qualitative study of physicians' and
      nurses' experience in a large university hospital.
AB  - BACKGROUND: Professional societies call for integration of end-of-life
      discussions early in the trajectory of heart failure, yet it remains unclear
      where current practices stand in relation to these recommendations. We sought to
      describe the perceptions and attitudes of caregivers in cardiology regarding end
      of-life situations. METHODS: We performed a qualitative study using semi
      directive interviews in the cardiology department of a university teaching
      hospital in France. Physicians, nurses and nurses' aides working full-time in the
      department at the time of the study were eligible. Participants were asked to
      describe how they experienced end-of-life situations. Interviews were recorded,
      transcribed and coded using thematic analysis to identify major and secondary
      themes. RESULTS: All physicians (N = 16)(average age 43.5 +/- 13 years), 16
      nurses (average age 38.5 +/- 7.6 years) and 5 nurses' aides (average age 49 +/-
      7.8 years) participated. Interviews were held between 30 March and 17 July 2017.
      The main themes to emerge from the physicians' discourse were the concept of
      cardiology being a very active discipline, and a very curative frame of mind was
      prevalent. Communication (with paramedical staff, patients and families) was
      deemed to be important. Advance directives were thought to be rare, and not
      especially useful. Nurses also reported communication as a major issue, but their
      form of communication is bounded by several factors (physicians' prior discourse,
      legislation). They commonly engage in reconciling: between the approach (curative
      or palliative) and the reality of the treatment prescribed; performing curative
      interventions in patients they deem to be dying cases causes them distress. The
      emergency context prevents nurses from taking the time necessary to engage in end
      of-life discussions. They engage in comfort-giving behaviors to maximize patient
      comfort. CONCLUSION: Current perceptions and practices vis-a-vis end-of-life
      situations in our department are individual, heterogeneous and not yet aligned
      with recommendations of professional societies.

PMID- 30290819
TI  - Anatomical basis for the choice of laparoscopic surgery for low rectal cancer
      through the pelvic imaging data-a cohort study.
AB  - BACKGROUND: Low rectal cancer surgery without anus conservation needs permanent
      ileostomy or colostomy which seriously affects the quality of life of patients.
      Therefore, low rectal cancer surgery not only pays attention to the safety of
      surgical treatment but also to the anus conservation. METHODS: Sixty-seven
      patients suffering from low rectal cancer had undergone laparoscopic surgery
      which was analyzed through retrospective study. They were divided into the anus
      conserving and non-anus-conserving groups. Thirty-five set of pelvic data was
      obtained from the preoperative CT and MRI images. After that, the discriminant
      function was obtained to predict the surgery methods for patients with low rectal
      carcinoma. RESULTS: Anal-conserving group discriminant function (F1) = - 33.698 +
      6.045 * anal margin distance (cm) + 1.105 * T4; non-anus-conserving group
      discriminant function (F2) = - 14.125 + 3.138 * anal margin distance (cm) + 0.804
      * T4. If F1 is greater than F2, then the case can be treated as the anus
      reservation while if F2 is greater than F1 the case cannot be treated anus
      reservation. The accuracy of the discriminant function was evaluated which was
      found to be 97%. CONCLUSION: The discriminant function of pelvic data provides
      anatomical basis for the choice of surgical methods for low rectal cancer.

PMID- 30290820
TI  - The analgesic effects of buprenorphine (Vetergesic or Simbadol) in combination
      with carprofen in dogs undergoing ovariohysterectomy: a randomized, blinded,
      clinical trial.
AB  - BACKGROUND: Buprenorphine is a potent lipophilic opioid analgesic that is largely
      used in the multimodal treatment of acute pain. Simbadol (buprenorphine
      hydrochloride) is the first and only FDA-approved high-concentration formulation
      of buprenorphine for use in cats. The aim of this study was to evaluate the
      analgesic efficacy of carprofen in combination with one of two commercial
      formulations of buprenorphine (Simbadol and Vetergesic, 1.8 mg/mL and 0.3 mg/mL,
      respectively) in dogs undergoing ovariohysterectomy. Twenty-four dogs were
      included in a randomized, prospective, controlled, clinical trial. Patients were
      randomly divided into 2 groups as follows. Dogs were premedicated with
      acepromazine (0.02 mg/kg) and either 0.02 mg/kg of Vetergesic or Simbadol
      intramuscularly (Vetergesic group - VG; Simbadol group - SG, respectively; n =
      12/group). General anesthesia was induced with propofol and maintained with
      isoflurane in 100% oxygen. Carprofen (4.4 mg/kg SC) was administered after
      induction of anesthesia. Heart rate, respiratory rate, blood pressure, pulse
      oximetry, pain scores using the Glasgow Composite Pain Scale Short Form (CMPS
      SF), sedation scores using a dynamic interactive visual analogue scale and
      adverse events were evaluated before and after ovariohysterectomy by an observer
      who was unaware of treatment administration. If CMPS-SF scores were >= 5/20, dogs
      were administered rescue analgesia (morphine 0.5 mg/kg IM). Statistical analysis
      was performed using linear mixed models and Fisher's exact test (p < 0.05).
      RESULTS: Pain and sedation scores and physiological parameters were not
      significantly different between treatments. Three dogs in VG (25%) and none in SG
      (0%) required rescue analgesia (p = 0.109). Adverse effects (i.e. vomiting and
      melena) were observed in two dogs in SG and were thought to be related to stress
      and/or nonsteroidal anti-inflammatory drug toxicity. CONCLUSIONS: The
      administration of buprenorphine with carprofen preoperatively provided adequate
      postoperative analgesia for the majority of dogs undergoing OVH without serious
      adverse events. Prevalence of rescue analgesia was not significantly different
      between groups; however, it could be clinically relevant and explained by a type
      II error (i.e. small sample size). Future studies are necessary to determine if
      analgesic efficacy after Simbadol and Vetergesic is related to individual
      variability or pharmacokinetic differences.

PMID- 30290821
TI  - Liposomal formulations of carboplatin injected by convection-enhanced delivery
      increases the median survival time of F98 glioma bearing rats.
AB  - BACKGROUND: Effectiveness of chemotherapy for treating glioblastoma (GBM) brain
      tumors is hampered by the blood-brain barrier which limits the entry into the
      brain of most drugs from the blood. To bypass this barrier, convection-enhanced
      delivery (CED) was proposed to directly inject drugs in tumor. However, the
      benefit of CED may be hampered when drugs diffuse outside the tumor to then
      induce neurotoxicity. Encapsulation of drugs into liposome aims at increasing
      tumor cells specificity and reduces neurotoxicity. However, the most appropriate
      liposomal formulation to inject drugs into brain tumor by CED still remains to be
      determined. In this study, four liposomal carboplatin formulations were prepared
      and tested in vitro on F98 glioma cells and in Fischer rats carrying F98 tumor
      implanted in the brain. Impact of pegylation on liposomal surface and relevance
      of positive or negative charge were assessed. RESULTS: The cationic non-pegylated
      (L1) and pegylated (L2) liposomes greatly improved the toxicity of carboplatin in
      vitro compared to free carboplatin, whereas only a modest improvement and even a
      reduction of efficiency were measured with the anionic non-pegylated (L3) and the
      pegylated (L4) liposomes. Conversely, only the L4 liposome significantly
      increased the median survival time of Fisher rats implanted with the F98 tumor,
      compared to free carboplatin. Neurotoxicity assays performed with the empty L4'
      liposome showed that the lipid components of L4 were not toxic. These results
      suggest that the positive charge on liposomes L1 and L2, which is known to
      promote binding to cell membrane, facilitates carboplatin accumulation in cancer
      cells explaining their higher efficacy in vitro. Conversely, negatively charged
      and pegylated liposome (L4) seems to diffuse over a larger distance in the tumor,
      and consequently significantly increased the median survival time of the animals.
      CONCLUSIONS: Selection of the best liposomal formulation based on in vitro
      studies or animal model can result in contradictory conclusions. The negatively
      charged and pegylated liposome (L4) which was the less efficient formulation in
      vitro showed the best therapeutic effect in animal model of GBM. These results
      support that relevant animal model of GBM must be considered to determine the
      optimal physicochemical properties of liposomal formulations.

PMID- 30290822
TI  - Self-nanoemulsifying system improves oral absorption and enhances anti-acute
      myeloid leukemia activity of berberine.
AB  - BACKGROUND: Recently, we found that berberine (BBR) exerts anti-acute myeloid
      leukemia activity, particularly toward high-risk and relapsed/refractory acute
      myeloid leukemia MV4-11 cells in vitro. However, the poor water solubility and
      low bioavailability observed with oral BBR administration has limited its
      clinical use. Therefore, we design and develop a novel oil-in-water self
      nanoemulsifying system for BBR (BBR SNE) to improve oral bioavailability and
      enhance BBR efficacy against acute myeloid leukemia by greatly improving its
      solubility. RESULTS: This system (size 23.50 +/- 1.67 nm, zeta potential - 3.35
      +/- 0.03 mV) was prepared with RH40 (surfactant), 1,2-propanediol (co
      surfactant), squalene (oil) and BBR using low-energy emulsification methods. The
      system loaded BBR successfully according to thermal gravimetric, differential
      scanning calorimetry, and Fourier transform infrared spectroscopy analyses. The
      release profile results showed that BBR SNE released BBR more slowly than BBR
      solution. The relative oral bioavailability of this novel system in rabbits was
      significantly enhanced by 3.41-fold over that of BBR. Furthermore, Caco-2 cell
      monolayer transport studies showed that this system could help enhance permeation
      and prevent efflux of BBR. Importantly, mice with BBR SNE treatment had
      significantly longer survival time than BBR-treated mice (P < 0.001) in an MV4-11
      engrafted leukemia murine model. CONCLUSIONS: These studies confirmed that BBR
      SNE is a promising therapy for acute myeloid leukemia.

PMID- 30290823
TI  - Identifying patterns of care for elderly patients with non-surgically treated
      stage III non-small cell lung cancer: an analysis of the national cancer
      database.
AB  - BACKGROUND: To compare patterns of care for elderly patients versus non-elderly
      patients with non-surgically treated stage III non-small cell lung cancer (NSCLC)
      using the National Cancer Database (NCDB). We hypothesize that elderly patients
      are less likely to receive curative treatments, including concurrent
      chemoradiation (CCRT), compared to non-elderly patients. METHODS: We identified
      patients from the NCDB between 2003 and 2014 with non-surgically treated stage
      III NSCLC. We defined elderly as >=70 years old and non-elderly <70 years old.
      Treatment categories included: no treatment, palliative treatment (chemotherapy
      alone, radiation (RT) alone <59.4 Gy or chemoradiation (CRT) <59.4 Gy), or
      definitive treatment (RT alone >=59.4 Gy or CRT >=59.4 Gy). Differences in
      treatment between elderly and non-elderly were tested using the chi2 test.
      RESULTS: We identified 57,602 elderly and 55,928 non-elderly patients. More
      elderly patients received no treatment (24.5% vs. 13.2%, P < 0.0001) and the
      elderly were less likely to receive definitive treatment (48.5% vs. 56.3%, P <
      0.0001). CCRT was delivered in a significantly smaller proportion of elderly vs.
      non-elderly patients (66.0% vs. 78.9%, P < 0.0001 in patients treated with
      definitive intent; 32.0% vs. 44.5%, P < 0.0001 in patients receiving any
      treatment; and 24.2% vs. 38.6%, P < 0.0001 amongst all patients). CONCLUSIONS: In
      this large study of patients with non-surgically treated stage III NSCLC, elderly
      patients were less likely to receive any treatment or treatment with definitive
      intent compared to the non-elderly. The lack of use of concurrent or sequential
      chemotherapy in the elderly with stage III NSCLC suggests that the optimal
      treatment approach for this vulnerable population remains undefined.

PMID- 30290824
TI  - Influences on students' empathy in medical education: an exploratory interview
      study with medical students in their third and last year.
AB  - BACKGROUND: Empathy is beneficial for patients and physicians. It facilitates
      treatment and improves physical and psychosocial outcomes. The therapeutic
      relevance of empathy emphasizes the need to help medical students develop their
      empathic abilities. Our study aimed to identify factors which promote or hinder
      the development and expression of empathy in medical students during the course
      of their studies. METHODS: We interviewed 24 medical students (six male and six
      female students in their 6th semester as well as six male and six female students
      in their final clinical year) using semi-structured interviews. The interviews
      were recorded, transcribed verbatim and analyzed using Braun & Clarke's thematic
      analysis. RESULTS: We identified four main themes influencing the development and
      expression of empathy. 1) Course of studies: hands-on-experience, role models,
      science and theory, and emphasis on the importance of empathy; 2) students:
      insecurities and lack of routine, increasing professionalism, previous work
      experiences, professional distance, mood, maturity, and personal level of
      empathy; 3) patients: "easy" and "difficult" patients including their state of
      health; and 4) surrounding conditions: time pressure/stress, work environment,
      and job dissatisfaction. CONCLUSIONS: The development and use of empathy could be
      promoted by increasing: hands-on-experiences, possibilities to experience the
      patient's point of view and offering patient contact early in the curriculum.
      Students need support in reflecting on their actions, behavior and experiences
      with patients. Instructors need time and opportunities to reflect on their own
      communication with and treatment of patients, on their teaching behavior, and on
      their function as role models for treating patients empathically and preventing
      stress. Practical experiences should be made less stressful for students. The
      current changes implemented in some medical school curriculums (e.g., in Germany)
      seem to go in the right direction by integrating patient contact early on in the
      curriculum and focusing more on teaching adequate communication and interaction
      behaviors.

PMID- 30290826
TI  - Comparison between procalcitonin and C-reactive protein to predict blood culture
      results in ICU patients.

PMID- 30290825
TI  - Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for the
      treatment of uncomplicated malaria in Papua New Guinea.
AB  - BACKGROUND: In 2009, the Papua New Guinea (PNG) Department of Health adopted
      artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) as the
      first- and second-line treatments for uncomplicated malaria, respectively. This
      study was conducted to assess the efficacy of both drugs following adoption of
      the new policy. METHODS: Between June 2012 and September 2014, a therapeutic
      efficacy study was conducted in East Sepik and Milne Bay Provinces of PNG in
      accordance with the standard World Health Organization (WHO) protocol for
      surveillance of anti-malarial drug efficacy. Patients >= 6 months of age with
      microscopy confirmed Plasmodium falciparum or Plasmodium vivax mono-infections
      were enrolled, treated with AL or DHA-PPQ, and followed up for 42 days. Study
      endpoints were adequate clinical and parasitological response (ACPR) on days 28
      and 42. The in vitro efficacy of anti-malarials and the prevalence of selected
      molecular markers of resistance were also determined. RESULTS: A total of 274 P.
      falciparum and 70 P. vivax cases were enrolled. The day-42 PCR-corrected ACPR for
      P. falciparum was 98.1% (104/106) for AL and 100% (135/135) for DHA-PPQ. The day
      42 PCR-corrected ACPR for P. vivax was 79.0% (15/19) for AL and 92.3% (36/39) for
      DHA-PPQ. Day 3 parasite clearance of P. falciparum was 99.2% with AL and 100%
      with DHA-PPQ. In vitro testing of 96 samples revealed low susceptibility to
      chloroquine (34% of samples above IC50 threshold) but not to lumefantrine (0%).
      Molecular markers assessed in a sub-set of the study population indicated high
      rates of chloroquine resistance in P. falciparum (pfcrt SVMNT: 94.2%, n = 104)
      and in P. vivax (pvmdr1 Y976F: 64.8%, n = 54). CONCLUSIONS: AL and DHA-PPQ were
      efficacious as first- and second-line treatments for uncomplicated malaria in
      PNG. Continued in vivo efficacy monitoring is warranted considering the threat of
      resistance to artemisinin and partner drugs in the region and scale-up of
      artemisinin-based combination therapy in PNG.

PMID- 30290827
TI  - Focal ischemic stroke leads to lung injury and reduces alveolar macrophage
      phagocytic capability in rats.
AB  - BACKGROUND: Ischemic stroke causes brain inflammation, which we postulate may
      result in lung damage. Several studies have focused on stroke-induced
      immunosuppression and lung infection; however, the possibility that strokes may
      trigger lung inflammation has been overlooked. We hypothesized that even focal
      ischemic stroke might induce acute systemic and pulmonary inflammation, thus
      altering respiratory parameters, lung tissue integrity, and alveolar macrophage
      behavior. METHODS: Forty-eight Wistar rats were randomly assigned to ischemic
      stroke (Stroke) or sham surgery (Sham). Lung function, histology, and
      inflammation in the lung, brain, bronchoalveolar lavage fluid (BALF), and
      circulating plasma were evaluated at 24 h. In vitro, alveolar macrophages from
      naive rats (unstimulated) were exposed to serum or BALF from Sham or Stroke
      animals to elucidate possible mechanisms underlying alterations in alveolar
      macrophage phagocytic capability. Alveolar macrophages and epithelial and
      endothelial cells of Sham and Stroke animals were also isolated for evaluation of
      mRNA expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha.
      RESULTS: Twenty-four hours following ischemic stroke, the tidal volume,
      expiratory time, and mean inspiratory flow were increased. Compared to Sham
      animals, the respiratory rate and duty cycle during spontaneous breathing were
      reduced, but this did not affect lung mechanics during mechanical ventilation.
      Lungs from Stroke animals showed clear evidence of increased diffuse alveolar
      damage, pulmonary edema, and inflammation markers. This was associated with an
      increase in ultrastructural damage, as evidenced by injury to type 2 pneumocytes
      and endothelial cells, cellular infiltration, and enlarged basement membrane
      thickness. Protein levels of proinflammatory mediators were documented in the
      lung, brain, and plasma (TNF-alpha and IL-6) and in BALF (TNF-alpha). The
      phagocytic ability of macrophages was significantly reduced. Unstimulated
      macrophages isolated from naive rats only upregulated expression of TNF-alpha and
      IL-6 following exposure to serum from Stroke rats. Exposure to BALF from Stroke
      or Sham animals did not change alveolar macrophage behavior, or gene expression
      of TNF-alpha and IL-6. IL-6 expression was increased in macrophages and
      endothelial cells from Stroke animals. CONCLUSIONS: In rats, focal ischemic
      stroke is associated with brain-lung crosstalk, leading to increased pulmonary
      damage and inflammation, as well as reduced alveolar macrophage phagocytic
      capability, which seems to be promoted by systemic inflammation.

PMID- 30290829
TI  - Noise in the intensive care unit and its influence on sleep quality: a
      multicenter observational study in Dutch intensive care units.
AB  - BACKGROUND: High noise levels in the intensive care unit (ICU) are a well-known
      problem. Little is known about the effect of noise on sleep quality in ICU
      patients. The study aim is to determine the effect of noise on subjective sleep
      quality. METHODS: This was a multicenter observational study in six Dutch ICUs.
      Noise recording equipment was installed in 2-4 rooms per ICU. Adult patients were
      eligible for the study 48 h after ICU admission and were followed up to maximum
      of five nights in the ICU. Exclusion criteria were presence of delirium and/or
      inability to be assessed for sleep quality. Sleep was evaluated using the
      Richards Campbell Sleep Questionnaire (range 0-100 mm). Noise recordings were
      used for analysis of various auditory parameters, including the number and
      duration of restorative periods. Hierarchical mixed model regression analysis was
      used to determine associations between noise and sleep. RESULTS: In total, 64
      patients (68% male), mean age 63.9 (+/- 11.7) years and mean Acute Physiology And
      Chronic Health Evaluation (APACHE) II score 21.1 (+/- 7.1) were included. Average
      sleep quality score was 56 +/- 24 mm. The mean of the 24-h average sound pressure
      levels (LAeq, 24h) was 54.0 dBA (+/- 2.4). Mixed-effects regression analyses
      showed that background noise (beta = - 0.51, p < 0.05) had a negative impact on
      sleep quality, whereas number of restorative periods (beta = 0.53, p < 0.01) and
      female sex (beta = 1.25, p < 0.01) were weakly but significantly correlated with
      sleep. CONCLUSIONS: Noise levels are negatively associated and restorative
      periods and female gender are positively associated with subjective sleep quality
      in ICU patients. TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT01826799 .
      Registered on 9 April 2013.

PMID- 30290828
TI  - Decoding the role of TET family dioxygenases in lineage specification.
AB  - Since the discovery of methylcytosine oxidase ten-eleven translocation (TET)
      proteins, we have witnessed an exponential increase in studies examining their
      roles in epigenetic regulation. TET family proteins catalyze the sequential
      oxidation of 5-methylcytosine (5mC) to oxidized methylcytosines including 5
      hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine. TETs
      contribute to the regulation of lineage-specific gene expression via modulating
      DNA 5mC/5hmC balances at the proximal and distal regulatory elements of cell
      identity genes, and therefore enhance chromatin accessibility and gene
      transcription. Emerging evidence suggests that TET dioxygenases participate in
      the establishment and/or maintenance of hypomethylated bivalent domains at
      multiple differentiation-associated genes, and thus ensure developmental
      plasticity. Here, we review the current state of knowledge concerning TET family
      proteins, DNA hydroxymethylation, their distribution, and function in endoderm,
      mesoderm, and neuroectoderm specification. We will summarize the evidence
      pertaining to their crucial regulatory roles in lineage commitment and
      development.

PMID- 30290830
TI  - Reconstruction of avian ancestral karyotypes reveals differences in the
      evolutionary history of macro- and microchromosomes.
AB  - BACKGROUND: Reconstruction of ancestral karyotypes is critical for our
      understanding of genome evolution, allowing for the identification of the gross
      changes that shaped extant genomes. The identification of such changes and their
      time of occurrence can shed light on the biology of each species, clade and their
      evolutionary history. However, this is impeded by both the fragmented nature of
      the majority of genome assemblies and the limitations of the available software
      to work with them. These limitations are particularly apparent in birds, with
      only 10 chromosome-level assemblies reported thus far. Algorithmic approaches
      applied to fragmented genome assemblies can nonetheless help define patterns of
      chromosomal change in defined taxonomic groups. RESULTS: Here, we make use of the
      DESCHRAMBLER algorithm to perform the first large-scale study of ancestral
      chromosome structure and evolution in birds. This algorithm allows us to
      reconstruct the overall genome structure of 14 key nodes of avian evolution from
      the Avian ancestor to the ancestor of the Estrildidae, Thraupidae and
      Fringillidae families. CONCLUSIONS: Analysis of these reconstructions provides
      important insights into the variability of rearrangement rates during avian
      evolution and allows the detection of patterns related to the chromosome
      distribution of evolutionary breakpoint regions. Moreover, the inclusion of
      microchromosomes in our reconstructions allows us to provide novel insights into
      the evolution of these avian chromosomes, specifically.

PMID- 30290831
TI  - Evaluation of patient- versus provider-collected vaginal swabs for microbiome
      analysis during pregnancy.
AB  - OBJECTIVE: We aimed to evaluate if patient- and provider-collected vaginal swabs
      in pregnant women reflect similar bacterial community characteristics. Pregnant
      patients performed a self-collected vaginal swab, then underwent a provider
      collected swab via speculum exam. DNA pyrosequencing of the 16S rRNA gene V1V3
      and V3V5 variable regions was performed. Relative abundance of taxa, alpha
      diversity, and beta diversity of patient- and provider-collected swabs were
      compared. RESULTS: Ninety-four vaginal swabs from 47 women were analyzed. On non
      metric multi-dimensional scaling plots, paired patient- and provider-collected
      swabs clustered closely. The median Pearson correlation coefficient was 0.993
      (interquartile range 0.951-0.999) for V1V3 and 0.987 (interquartile range 0.902
      0.999) for V3V5. Among paired V1V3 and V3V5 sequences, 83.0% and 73.9% showed
      strong Pearson correlation (> 0.9), respectively, between patient- and provider
      collected swabs; V1V3 and V3V5 sequences with weaker Pearson correlation (< 0.9)
      had correlation coefficients 0.57-0.89 and 0.49-0.89, respectively. No taxa were
      preferentially detected by sampling method, with relative abundance of taxa
      highly conserved. No significant difference in Shannon diversity for V1V3 (p =
      0.22) and V3V5 (p = 0.11) sequences among paired samples was seen. We demonstrate
      that bacterial communities defined from patient- and provider-collected vaginal
      swabs in pregnant women are similar, validating utilization of patient-collected
      swabs for vaginal bacterial microbiome sampling during pregnancy.

PMID- 30290832
TI  - Long-term exposure to road traffic noise and incidence of breast cancer: a cohort
      study.
AB  - BACKGROUND: Exposure to road traffic noise was associated with increased risk of
      estrogen receptor (ER)-negative (ER-) breast cancer in a previous cohort study,
      but not with overall or ER-positive (ER+) breast cancer, or breast cancer
      prognosis. We examined the association between long-term exposure to road traffic
      noise and incidence of breast cancer, overall and by ER and progesterone receptor
      (PR) status. METHODS: We used the data from a nationwide Danish Nurse Cohort on
      22,466 female nurses (age > 44 years) who at recruitment in 1993 or 1999 reported
      information on breast cancer risk factors. We obtained data on the incidence of
      breast cancer from the Danish Cancer Registry, and on breast cancer subtypes by
      ER and PR status from the Danish Breast Cancer Cooperative Group, up to 31
      December 2012. Road traffic noise levels at the nurses' residences were estimated
      by the Nord2000 method between 1970 and 2013 as annual means of a weighted 24 h
      average (Lden) at the most exposed facade. We used time-varying Cox regression to
      analyze the associations between the 24-year, 10-year, and 1-year mean of Lden
      and breast cancer, separately for total breast cancer and by ER and PR status.
      RESULTS: Of the 22,466 women, 1193 developed breast cancer in total during
      353,775 person-years of follow up, of whom 611 had complete information on ER and
      PR status. For each 10 dB increase in 24-year mean noise levels at their
      residence, we found a statistically significant 10% (hazard ratio and 95%
      confidence interval 1.10; 1.00-1.20) increase in total breast cancer incidence
      and a 17% (1.17; 1.02-1.33) increase in analyses based on 611 breast cancer cases
      with complete ER and PR information. We found positive, statistically significant
      association between noise levels and ER+ (1.23; 1.06-1.43, N = 494) but not ER-
      (0.93; 0.70-1.25, N = 117) breast cancers, and a stronger association between
      noise levels and PR+ (1.21; 1.02-1.42, N = 393) than between noise levels and PR-
      (1.10; 0.89-1.37, N = 218) breast cancers. Association between noise and ER+
      breast cancer was statistically significantly stronger in nurses working night
      shifts (3.36; 1.48-7.63) than in those not working at night (1.21; 1.02-1.43) (p
      value for interaction = 0.05). CONCLUSION: Long-term exposure to road traffic
      noise may increase risk of ER+ breast cancer.

PMID- 30290834
TI  - Comparing lethal dose ratios using probit regression with arbitrary slopes.
AB  - BACKGROUND: Evaluating the toxicity or effectiveness of two or more toxicants in
      a specific population often requires specialized statistical software to
      calculate and compare median lethal doses (LD50s). Tests for equality of LD50s
      using probit regression with parallel slopes have been implemented in many
      software packages, while tests for cases of arbitrary slopes are not generally
      available. METHODS: In this study, we established probit-log(dose) regression
      models and solved them by the maximum likelihood method using Microsoft Excel.
      The z- and chi2-tests were used to assess significance and goodness of fit to the
      probit regression models, respectively. We calculated the lethal doses (LDs) of
      the toxicants at different significance levels and their 95% confidence limits
      (CLs) based on an accurate estimation of log(LD) variances. We further calculated
      lethal dose ratios and their 95% CLs for two examples without assuming parallel
      slopes following the method described by Robertson, et al., 2017. RESULTS: We
      selected representative toxicology datasets from the literature as case studies.
      For datasets without natural responses in the control group, the slopes,
      intercepts, chi2 statistics and LDs calculated using our method were identical to
      those calculated using Polo-Plus and SPSS software, and the 95% CLs of the lethal
      dose ratios between toxicants were close to those calculated using Polo-Plus. For
      datasets that included natural responses in the control group, our results were
      also close to those calculated using Polo-Plus and SPSS. CONCLUSION: This
      procedure yielded accurate estimates of lethal doses and 95% CLs at different
      significance levels as well as the lethal dose ratios and 95% CLs between two
      examples. The procedure could be used to assess differences in the toxicities of
      two examples without the assumption of parallelism between probit-log(dose)
      regression lines.

PMID- 30290835
TI  - A rare case of large pyosalpinx in an elderly patient with well-controlled type 2
      diabetes mellitus: a case report.
AB  - BACKGROUND: Pyosalpinx, which is one of the pelvic inflammatory diseases, is
      usually observed in young women; it is rarely found in older women. Possible
      causative agents are thought to be Chlamydia trachomatis and Neisseria gonorrhea
      in addition to some Enterobacteriaceae. On the other hand, type 2 diabetes is a
      disease with a lot of complications such as hyperglycemia, inflammation, and
      immune disorders. Therefore, patients with type 2 diabetes mellitus have an
      increased susceptibility to infection especially when glycemic control is poor.
      CASE PRESENTATION: We experienced a rare case of large pyosalpinx in an elderly
      patient with well-controlled type 2 diabetes mellitus. A 72-year-old Japanese
      woman with a 10-year history of type 2 diabetes mellitus had symptoms of diarrhea
      and persistent pain in left lower abdomen. She had mild tenderness to palpation
      in her abdomen. Inflammation markers were markedly elevated. Her abdominal
      computed tomography and magnetic resonance imaging on admission revealed a tumor
      in left side of intrapelvis and we diagnosed her as having pyosalpinx. Pathogenic
      bacteria were not detected. On admission, her glycemic control was relatively
      good; in addition, her glycated hemoglobin levels were around 6% for over 1 year.
      Although pathogenic bacteria were not detected, we started antibiotics therapy.
      Fourteen days after starting the antibiotics her laboratory data were improved.
      Three months later, the tumor was markedly smaller compared to that on admission.
      CONCLUSIONS: We should keep in mind that older patients with type 2 diabetes
      mellitus are immunocompromised hosts and thereby they could have rare pelvic
      inflammatory disease such as pyosalpinx even when good glycemic control is
      obtained for a long period of time.

PMID- 30290836
TI  - Sequential MRI in pontine and extrapontine myelinolysis following rapid
      correction of hyponatremia.
AB  - OBJECTIVE: This study describes the MRI changes associated with pontine and
      extrapontine myelinolysis secondary to rapid correction of hyponatremia in dogs.
      The authors discuss the relevance of the results for theories of pathogenesis and
      for diagnosis of patients. RESULTS: MRI changes associated with pontine and
      extrapontine myelinolysis first occur on diffusion-weighted imaging. As a
      generalization, gadolinium enhancement, flair image change and T2 weighted image
      abnormality appear sequentially.

PMID- 30290833
TI  - Acidic microenvironment plays a key role in human melanoma progression through a
      sustained exosome mediated transfer of clinically relevant metastatic molecules.
AB  - BACKGROUND: Microenvironment cues involved in melanoma progression are largely
      unknown. Melanoma is highly influenced in its aggressive phenotype by the changes
      it determinates in its microenvironment, such as pH decrease, in turn influencing
      cancer cell invasiveness, progression and tissue remodelling through an abundant
      secretion of exosomes, dictating cancer strategy to the whole host. A role of
      exosomes in driving melanoma progression under microenvironmental acidity was
      never described. METHODS: We studied four differently staged human melanoma
      lines, reflecting melanoma progression, under microenvironmental acidic pHs
      pressure ranging between pH 6.0-6.7. To estimate exosome secretion as a function
      of tumor stage and environmental pH, we applied a technique to generate native
      fluorescent exosomes characterized by vesicles integrity, size, density, markers
      expression, and quantifiable by direct FACS analysis. Functional roles of
      exosomes were tested in migration and invasion tests. Then we performed a
      comparative proteomic analysis of acid versus control exosomes to elucidate a
      specific signature involved in melanoma progression. RESULTS: We found that
      metastatic melanoma secretes a higher exosome amount than primary melanoma, and
      that acidic pH increases exosome secretion when melanoma is in an intermediate
      stage, i.e. metastatic non-invasive. We were thus able to show that acidic pH
      influences the intercellular cross-talk mediated by exosomes. In fact when
      exposed to exosomes produced in an acidic medium, pH naive melanoma cells acquire
      migratory and invasive capacities likely due to transfer of metastatic exosomal
      proteins, favoring cell motility and angiogenesis. A Prognoscan-based meta
      analysis study of proteins enriched in acidic exosomes, identified 11 genes
      (HRAS, GANAB, CFL2, HSP90B1, HSP90AB1, GSN, HSPA1L, NRAS, HSPA5, TIMP3, HYOU1),
      significantly correlating with poor prognosis, whose high expression was in part
      confirmed in bioptic samples of lymph node metastases. CONCLUSIONS: A crucial
      step of melanoma progression does occur at melanoma intermediate -stage, when
      extracellular acidic pH induces an abundant release and intra-tumoral uptake of
      exosomes. Such exosomes are endowed with pro-invasive molecules of clinical
      relevance, which may provide a signature of melanoma advancement.

PMID- 30290837
TI  - Chemical crystal identification with deep learning machine vision.
AB  - OBJECTIVE: This study was carried out with the purpose of testing the ability of
      deep learning machine vision to identify microscopic objects and geometries found
      in chemical crystal structures. RESULTS: A database of 6994 images taken with a
      light microscope showing microscopic crystal details of selected chemical
      compounds along with 180 images of an unknown chemical was created to train and
      test, respectively the deep learning models. The models used were GoogLeNet (22
      layers deep network) and VGG-16 (16 layers deep network), based on the Caffe
      framework (University of California, Berkeley, CA) of the DIGITS platform (NVIDIA
      Corporation, Santa Clara, CA). The two models were successfully trained with the
      images, having validation accuracy values of 97.38% and 99.65% respectively.
      Finally, both models were able to correctly identify the unknown chemical sample
      with a high probability score of 93.34% (GoogLeNet) and 99.41% (VGG-16). The
      positive results found in this study can be further applied to other unknown
      sample identification tasks using light microscopy coupled with deep learning
      machine vision.

PMID- 30290840
TI  - Development of a core outcome set (COS) and selecting outcome measurement
      instruments (OMIs) for non-valvular atrial fibrillation in traditional Chinese
      medicine clinical trials: study protocol.
AB  - BACKGROUND: An increasing number of clinical trials of traditional Chinese
      medicine are being conducted in the treatment of non-valvular atrial fibrillation
      (NVAF) in China. However, the heterogeneity of outcomes and outcome measurement
      instruments has produced little evidence for traditional Chinese medicine in
      treating NVAF because many trials cannot be included in a meta-analysis. The
      majority of the trials did not report endpoint outcomes, side effects or other
      important outcomes for patients, which makes it difficult to evaluate the
      efficacy and safety of traditional Chinese medicine. Therefore, it is important
      to develop a core outcome set (COS). Although there are two related COSs for
      clinical trials of atrial fibrillation, the methodology is limited, and the
      perspectives of Chinese experts and patients are unclear. Therefore, we will
      develop a COS and recommend outcome measurement instruments after finishing the
      COS, which can be used for clinical trials of traditional Chinese medicine in
      NVAF. METHODS/DESIGN: The method of the study will include eight stages led by a
      national multidisciplinary Steering Committee: (1) A systematic review will be
      developed to identify currently reported outcomes and traditional Chinese
      medicine syndromes in clinical trials of NVAF, (2) Semi-structured interviews of
      patients will be conducted to fill gaps in potential outcomes, (3) Traditional
      Chinese medicine syndrome names will be identified from medical records, (4) A
      dataset of traditional Chinese medicine syndrome names will be developed, (5) The
      investigation of traditional Chinese medicine syndromes will be conducted from
      cross-sectional study, (6) Two rounds of Delphi surveys will be carried out, (7)
      A consensus meeting will be conducted to develop a COS, and (8) Recommendations
      of outcome measurement instruments (OMIs), which should be used in the COS, will
      be developed. DISCUSSION: The COS will improve the consistency of outcome
      reporting and reduce the reporting bias in NVAF clinical trials of traditional
      Chinese medicine to improve the value of traditional Chinese medicine clinical
      trials. TRIAL REGISTRATION: This study is not a clinical trial, so it is
      registered in Core Outcome Measures in Effectiveness Trials Initiative (COMET).
      Registration number: 941 . Registered on 22 December 2016.

PMID- 30290838
TI  - ADAR1-mediated RNA-editing of 3'UTRs in breast cancer.
AB  - BACKGROUND: Whole transcriptome RNA variant analyses have shown that adenosine
      deaminases acting on RNA (ADAR) enzymes modify a large proportion of cellular
      RNAs, contributing to transcriptome diversity and cancer evolution. Despite the
      advances in the understanding of ADAR function in breast cancer, ADAR RNA editing
      functional consequences are not fully addressed. RESULTS: We characterized A to
      G(I) mRNA editing in 81 breast cell lines, showing increased editing at 3'UTR and
      exonic regions in breast cancer cells compared to immortalized non-malignant cell
      lines. In addition, tumors from the BRCA TCGA cohort show a 24% increase in
      editing over normal breast samples when looking at 571 well-characterized UTRs
      targeted by ADAR1. Basal-like subtype breast cancer patients with high level of
      ADAR1 mRNA expression shows a worse clinical outcome and increased editing in
      their 3'UTRs. Interestingly, editing was particularly increased in the 3'UTRs of
      ATM, GINS4 and POLH transcripts in tumors, which correlated with their mRNA
      expression. We confirmed the role of ADAR1 in this regulation using a shRNA in a
      breast cancer cell line (ZR-75-1). CONCLUSIONS: Altogether, these results
      revealed a significant association between the mRNA editing in genes related to
      cancer-relevant pathways and clinical outcomes, suggesting an important role of
      ADAR1 expression and function in breast cancer.

PMID- 30290839
TI  - Clinical significance in pediatric oncology randomized controlled treatment
      trials: a systematic review.
AB  - BACKGROUND: Clinical significance in a randomized controlled trial (RCT) can be
      determined using the minimal clinically important difference (MCID), which should
      inform the delta value used to determine sample size. The primary objective was
      to assess clinical significance in the pediatric oncology randomized controlled
      trial (RCT) treatment literature by evaluating: (1) the relationship between the
      treatment effect and the delta value as reported in the sample size calculation,
      and (2) the concordance between statistical and clinical significance. The
      secondary objective was to evaluate the reporting of methodological attributes
      related to clinical significance. METHODS: RCTs of pediatric cancer treatments,
      where a sample size calculation with a delta value was reported or could be
      calculated, were systematically reviewed. MEDLINE, EMBASE, and the Cochrane
      Childhood Cancer Group Specialized Register through CENTRAL were searched from
      inception to July 2016. RESULTS: RCTs (77 overall; 11 and 66), representing 95
      (13 and 82) randomized questions were included for non-inferiority and
      superiority RCTs (herein, respectively). The minority (22.1% overall; 76.9 and
      13.4%) of randomized questions reported conclusions based on clinical
      significance, and only 4.2% (15.4 and 2.4%) explicitly based the delta value on
      the MCID. Over half (67.4% overall; 92.3 and 63.4%) reported a confidence
      interval or standard error for the primary outcome experimental and control
      values and 12.6% (46.2 and 7.3%) reported the treatment effect, respectively. Of
      the 47 randomized questions in superiority trials that reported statistically non
      significant findings, 25.5% were possibly clinically significant. Of the 24
      randomized questions in superiority trials that were statistically significant,
      only 8.3% were definitely clinically significant. CONCLUSIONS: A minority of RCTs
      in the pediatric oncology literature reported methodological attributes related
      to clinical significance and a notable portion of statistically insignificant
      studies were possibly clinically significance.

PMID- 30290842
TI  - Just how plain are plain tobacco packs: re-analysis of a systematic review using
      multilevel meta-analysis suggests lessons about the comparative benefits of
      synthesis methods.
AB  - BACKGROUND: Comparisons between narrative synthesis and meta-analysis as
      synthesis methods in systematic reviews are uncommon within the same systematic
      review. We re-analysed a systematic review on the effects of plain packaging of
      tobacco on attractiveness. We sought to compare different synthesis approaches
      within the same systematic review and shed light on the comparative benefits of
      each approach. METHODS: In our re-analysis, we included results relating to
      attractiveness in included reports. We extracted findings from studies and
      converted all estimates of differences in attractiveness to Cohen's d. We used
      multilevel meta-analysis to account for clustering of effect sizes within
      studies. RESULTS: Of the 19 studies reporting results on attractiveness, seven
      studies that included between-subjects analyses could be included in the meta
      analysis. Plain packs were less attractive than branded packs (d = - 0.59, 95% CI
      [- 0.71, - 0.47]), with negligible but uncertain between-studies heterogeneity
      (I2 = 0%, 95% CI [0.00, 70.81]) and high within-study heterogeneity (I2 = 92.6%,
      95% CI [91.04, 93.90]). CONCLUSIONS: The meta-analysis found, similar to the
      narrative synthesis, that respondents typically rated plain packaging as less
      attractive than alternative (e.g. branded) tobacco packs. However, there were
      several trade-offs between analysis methods in the types and bodies of evidence
      each one contained and in the difference between partial precision and breadth of
      conclusions. Analysis methods were different in respect of the role of judgement
      and contextual variation and in terms of estimation and unexpected effect
      modification. In addition, we noted that analysis methods were different in how
      they accounted for heterogeneity and consistency.

PMID- 30290841
TI  - Evolutionary and developmental dynamics of sex-biased gene expression in common
      frogs with proto-Y chromosomes.
AB  - BACKGROUND: The patterns of gene expression on highly differentiated sex
      chromosomes differ drastically from those on autosomes, due to sex-specific
      patterns of selection and inheritance. As a result, X chromosomes are often
      enriched in female-biased genes (feminization) and Z chromosomes in male-biased
      genes (masculinization). However, it is not known how quickly sexualization of
      gene expression and transcriptional degeneration evolve after sex-chromosome
      formation. Furthermore, little is known about how sex-biased gene expression
      varies throughout development. RESULTS: We sample a population of common frogs
      (Rana temporaria) with limited sex-chromosome differentiation (proto-sex
      chromosome), leaky genetic sex determination evidenced by the occurrence of XX
      males, and delayed gonadal development, meaning that XY individuals may first
      develop ovaries before switching to testes. Using high-throughput RNA sequencing,
      we investigate the dynamics of gene expression throughout development, spanning
      from early embryo to froglet stages. Our results show that sex-biased expression
      affects different genes at different developmental stages and increases during
      development, reaching highest levels in XX female froglets. Additionally, sex
      biased gene expression depends on phenotypic, rather than genotypic sex, with
      similar expression in XX and XY males; correlates with gene evolutionary rates;
      and is not localized to the proto-sex chromosome nor near the candidate sex
      determining gene Dmrt1. CONCLUSIONS: The proto-sex chromosome of common frogs
      does not show evidence of sexualization of gene expression, nor evidence for a
      faster rate of evolution. This challenges the notion that sexually antagonistic
      genes play a central role in the initial stages of sex-chromosome evolution.

PMID- 30290845
TI  - Bougie-in-channel intubation technique.

PMID- 30290843
TI  - Modularity of genes involved in local adaptation to climate despite physical
      linkage.
AB  - BACKGROUND: Linkage among genes experiencing different selection pressures can
      make natural selection less efficient. Theory predicts that when local adaptation
      is driven by complex and non-covarying stresses, increased linkage is favored for
      alleles with similar pleiotropic effects, with increased recombination favored
      among alleles with contrasting pleiotropic effects. Here, we introduce a
      framework to test these predictions with a co-association network analysis, which
      clusters loci based on differing associations. We use this framework to study the
      genetic architecture of local adaptation to climate in lodgepole pine, Pinus
      contorta, based on associations with environments. RESULTS: We identify many
      clusters of candidate genes and SNPs associated with distinct environments,
      including aspects of aridity and freezing, and discover low recombination rates
      among some candidate genes in different clusters. Only a few genes contain SNPs
      with effects on more than one distinct aspect of climate. There is limited
      correspondence between co-association networks and gene regulatory networks. We
      further show how associations with environmental principal components can lead to
      misinterpretation. Finally, simulations illustrate both benefits and caveats of
      co-association networks. CONCLUSIONS: Our results support the prediction that
      different selection pressures favor the evolution of distinct groups of genes,
      each associating with a different aspect of climate. But our results went against
      the prediction that loci experiencing different sources of selection would have
      high recombination among them. These results give new insight into evolutionary
      debates about the extent of modularity, pleiotropy, and linkage in the evolution
      of genetic architectures.

PMID- 30290844
TI  - Anemia and other hematological profiles of pregnant women attending antenatal
      care in Debre Berhan Referral Hospital, North Shoa, Ethiopia.
AB  - OBJECTIVE: The aim of the study was to determine level of anemia and other
      hematological profiles in pregnant women attending antenatal care clinic in Debre
      Berhan Referral Hospital, Ethiopia. RESULTS: Prevalence of anemia was 2.8% and
      that of thrombocytopenia was 10.2%. Out of the anemic pregnant mothers, 5 (62.5%)
      were mildly anemic and 2 (25%) were severely anemic. The factor age < 20 years of
      mothers was significantly associated with anemia (P < 0.05). In addition, the
      occurrence of anemia in mothers who visited antenatal clinic two times is two
      times higher than those mother who visited the antenatal clinic three times.
      Moreover, the prevalence of anemia is two times more likely to occur in pregnant
      mothers who did not take iron supplements as compared to their counter parts.
      According to pregnancy periods; mean white blood cells count was (8.48 +/- 3.09,
      8.83 +/- 2.73, 8.86 +/- 2.67) * 109/L for the first, second and third trimesters,
      respectively. Red blood cells and platelet counts in the first trimester were
      significantly higher than their corresponding values in third trimester (P <
      0.01), whereas mean hemoglobin and hematocrit values were not statistically
      significant within trimesters (P > 0.05).

PMID- 30290847
TI  - Newcastle disease virus V protein inhibits apoptosis in DF-1 cells by
      downregulating TXNL1.
AB  - Many viral proteins are related to suppressing apoptosis in target cells and are
      hence beneficial to viral replication. The V protein of Newcastle disease virus
      (NDV) is one such protein that plays an important role in inhibiting apoptosis in
      a species-specific manner. However, to date, there have been no reports
      clarifying the antiapoptotic mechanisms of the V protein. The present study was
      undertaken to determine the apoptotic potential of the V protein in a chicken
      embryo fibroblast cell line (DF-1 cell) and to elucidate its molecular mechanisms
      of action. Here, a yeast two-hybrid system was used to screen the host proteins
      that interact with the V protein and identified thioredoxin-like protein 1
      (TXNL1) as a potential binding partner. Immuno-colocalization of V protein and
      TXNL1 protein in DF-1 cells further verified the interaction of the two proteins.
      Through the overexpression of TXNL1 protein and knockdown of TXNL1 protein in DF
      1 cells, the effects of NDV replication and cell apoptosis were examined. Cell
      apoptosis was detected by flow cytometry. The mRNA and protein expression levels
      of Bax, Bcl-2 and Caspase-3 were detected by quantitative real-time PCR (Q-PCR)
      and Western blotting. NDV expression was detected by Q-PCR and plaque assay. The
      results revealed that the TXNL1 protein induced apoptosis and inhibited NDV
      replication in DF-1 cells. Furthermore, the Western blot and Q-PCR results
      suggested that TXNL1 induced cell apoptosis through a pathway involving Bcl-2?Bax
      and Caspase-3. Finally, this work provides insight into the mechanism by which
      the V protein inhibits apoptosis.

PMID- 30290846
TI  - A conditional Pax6 depletion study with no morphological effect on the adult
      mouse corneal epithelium.
AB  - OBJECTIVE: The corneas of heterozygous Pax6+/- mice develop abnormally and
      deteriorate further after birth but it is not known whether the postnatal
      deterioration is predetermined by abnormal development. Our objective was to
      identify whether depletion of Pax6 in adult mice caused any corneal
      abnormalities, similar to those in Pax6+/- mice, where Pax6 levels are low
      throughout development and adulthood. We used two tamoxifen-inducible, Cre-loxP
      experimental strategies to deplete Pax6 either ubiquitously or in a restricted
      range of cell types. RESULTS: In a preliminary study, ubiquitous depletion of
      Pax6 by tamoxifen treatment of E9.5 CAG-CreERTg/-;Pax6fl/fl embryos affected eye
      development. Tamoxifen treatment of 12-week old, adult CAG-CreERTg/-;Pax6fl/+ and
      CAG-CreERTg/-;Pax6fl/fl mice resulted in weak and/or patchy Pax6 immunostaining
      in the corneal epithelium but caused no corneal abnormalities. GFP staining in
      tamoxifen-treated CAG-CreERTg/-;RCE:loxP reporter mice was also patchy. We
      attribute patchy Pax6 staining to mosaic deletion of the Pax6fl allele, probably
      caused by mosaic CAG-CreERTg expression. In a parallel study, we treated adult
      Krt19-CreERTg/-;Pax6fl/+ mice with tamoxifen to try to deplete Pax6 in limbal
      epithelial stem cells (LESCs) which replenish the corneal epithelium. However,
      Pax6 staining remained strong after a 12-week chase period so the Krt19-CreERTg/-
      transgene may have failed to target LESCs.

PMID- 30290848
TI  - High failure rate of proximal femoral locking plates in fixation of trochanteric
      fractures.
AB  - BACKGROUND: The aim of this study was to report our previous results of
      treatments for trochanteric fractures with proximal femoral locking plates (PFLP)
      and to analyze the underlying mechanisms and possible risk factors associated
      with the high failure rate of this technique. METHODS: From January 2010 to
      October 2014, 273 consecutive patients with trochanteric femoral fractures were
      identified, and 95 patients (with 97 fractures) ultimately met the inclusion
      criteria. Clinical records regarding demographic features and intraoperative data
      including total incision length, operation time, blood loss, and failures
      detected in radiographs were documented and assessed. The collected data were
      analyzed with SPSS 19.0 software. RESULTS: The stable group (AO/OTA 31 A1 and
      A2.1) had less blood loss than the unstable group (AO/OTA 31 A2.2, A2.3, and A3).
      The ultimate failure rate was 36% in 97 fractures. The obvious complications in
      this study included nonunion in 7 (7.2%) fractures, implant breakage in 4 (4.1%)
      fractures, varus deformity in 34 (35%) fractures, and loosening of the proximal
      femoral screw in 21 (21.6%) fractures. Six patients received reoperations. The
      total failure rate in the stable group was 17% and was 50% in the unstable group.
      In patients greater than 60 years old in the unstable group, the failure rate was
      60.5%. CONCLUSIONS: High failure rates of PFLP were observed in patients with
      trochanteric fracture, especially in patients who were greater than 60 years old
      with unstable fracture types. PFLP was not an appropriate treatment for
      trochanteric fractures.

PMID- 30290849
TI  - Effect of machine learning methods on predicting NSCLC overall survival time
      based on Radiomics analysis.
AB  - BACKGROUND: To investigate the effect of machine learning methods on predicting
      the Overall Survival (OS) for non-small cell lung cancer based on radiomics
      features analysis. METHODS: A total of 339 radiomic features were extracted from
      the segmented tumor volumes of pretreatment computed tomography (CT) images.
      These radiomic features quantify the tumor phenotypic characteristics on the
      medical images using tumor shape and size, the intensity statistics and the
      textures. The performance of 5 feature selection methods and 8 machine learning
      methods were investigated for OS prediction. The predicted performance was
      evaluated with concordance index between predicted and true OS for the non-small
      cell lung cancer patients. The survival curves were evaluated by the Kaplan-Meier
      algorithm and compared by the log-rank tests. RESULTS: The gradient boosting
      linear models based on Cox's partial likelihood method using the concordance
      index feature selection method obtained the best performance (Concordance Index:
      0.68, 95% Confidence Interval: 0.62~ 0.74). CONCLUSIONS: The preliminary results
      demonstrated that certain machine learning and radiomics analysis method could
      predict OS of non-small cell lung cancer accuracy.

PMID- 30290850
TI  - Correction to: Annexin A2 binds to vimentin and contributes to porcine
      reproductive and respiratory syndrome virus multiplication.
AB  - In the original publication of this article [1], the author found the brand of
      vimentin antibody was wrong in Fig. 3. The legend of Fig. 3, 'mouse anti-vimentin
      mAb (Cell Signaling Technology) at 4  degrees C overnight' should be 'mouse anti
      vimentin mAb (Sigma-Aldrich) at 4  degrees C overnight'.

PMID- 30290851
TI  - Behavioral economics-based incentives supported by mobile technology on HIV
      knowledge and testing frequency among Latino/a men who have sex with men and
      transgender women: Protocol for a randomized pilot study to test intervention
      feasibility and acceptability.
AB  - BACKGROUND: Mobile Technology and Incentives (MOTIVES) is a randomized pilot
      study of a mobile technology-based and behavioral economics-supported HIV
      prevention intervention. Behavioral economics (BE) uses financial incentives in a
      way that departs from the traditional focus on large monetary payments. Instead,
      BE suggests that relatively small "nudges" can effectively initiate and sustain
      behavior change. This pilot study examines the feasibility and acceptability of
      an HIV prevention intervention that uses text messages in combination with BE
      incentives to improve retention of HIV prevention information and increase
      frequency of HIV testing among Latino/a men who have sex with men (MSM) and
      transgender women (TGW). The pilot will also estimate mission-critical design
      parameters with point and confidence interval estimates of the intervention to
      inform a future, fully powered effectiveness study. METHODS: The project will be
      conducted in collaboration with Bienestar Human Services, Inc. (Bienestar), a non
      profit community-based service organization. The intervention is being tested in
      a small, randomized controlled trial to pilot the intervention's feasibility and
      acceptability among 200 Latino/a MSM and TGW from Bienestar's HIV testing sites.
      Information on feasibility will include recruitment, refusal, and retention rates
      as well as message sending success rates; acceptability will include perceived
      appropriateness based on responses to the intervention. Participants will be
      randomized into either the "information only" control group (e.g. receiving text
      messages with HIV prevention information) or the "information plus" intervention
      group (e.g. additionally receiving quiz questions that provide the possibility of
      winning prizes). Participants will be followed for 12 months from enrollment. In
      addition to using data abstracted from Bienestar's routine data collection
      mechanisms, we will also collect survey data (blinded outcome assessment) from
      participants at 0, 6, and 12 months to provide an initial assessment of whether
      incentives affect their level of HIV knowledge and testing frequency. DISCUSSION:
      If shown to be acceptable, feasible, and resource-efficient, MOTIVES will provide
      an innovative way to communicate the latest HIV prevention information and
      support trimestral HIV screening among Latino/a MSM and TGW. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT03144336 . Registered on 5 May 2017.

PMID- 30290854
TI  - Ionic Liquids Applied to Extraction of Xenobiotics from Food, Environmental, and
      Biological Samples and for Analysis by Liquid Chromatography.
AB  - Ionic liquids (ILs) are a class of unique substances composed purely by cation
      and anions. Because of the unique properties of ILs (e.g., electric conductivity,
      low volatility, thermostability, and tenability), their use has attracted
      considerable interest, including an increasing number of publications on their
      use in analytical separation techniques. ILs applied as extraction solvents in
      liquid-liquid extraction methods and promote interactions between the analyte and
      solvent because of their unique chemical functional groups. In solid-phase
      extraction, ILs are usually used for the modification of stationary phases. ILs
      in LC are applied as mobile phase additives to obtain a better peak shape and
      high system efficiency for the analysis of ionic, especially basic, compounds.
      This review highlights some of the applications of ILs to extraction and analysis
      by LC of xenobiotics in food, environmental, and biological samples.

PMID- 30290852
TI  - An early increase in endothelial protein C receptor is associated with excess
      mortality in pneumococcal pneumonia with septic shock in the ICU.
AB  - BACKGROUND: This study investigated changes in plasma level of soluble
      endothelial protein C receptor (sEPCR) in association with outcome in patients
      with septic shock. We explored sEPCR for early sepsis prognosis assessment and
      constructed a scoring system based on clinical and biological data, in order to
      discriminate between surviving at hospital discharge and non-surviving patients.
      METHODS: Clinical data and samples were extracted from the prospective
      "STREPTOGENE" cohort. We enrolled 278 patients, from 50 intensive care units
      (ICUs), with septic shock caused by pneumococcal pneumonia. Patients were divided
      into survivors (n = 194) and non-survivors (n = 84) based on in-hospital
      mortality. Soluble EPCR plasma levels were quantified at day 1 (D1) and day 2
      (D2) by ELISA. The EPCR gene A3 haplotype was determined. Patients were followed
      up until hospital discharge. Univariate and multivariate analyses were performed.
      A scoring system was constructed using least absolute shrinkage and selection
      operator (lasso) logistic regression for selecting predictive variables. RESULTS:
      In-hospital mortality was 30.2% (n = 84). Plasma sEPCR level was significantly
      higher at D1 and D2 in non-surviving patients compared to patients surviving to
      hospital discharge (p = 0.0447 and 0.0047, respectively). Early increase in sEPCR
      at D2 was found in non-survivors while a decrease was observed in the survival
      group (p = 0.0268). EPCR A3 polymorphism was not associated with mortality.
      Baseline sEPCR level and its variation from D1 to D2 were independent predictors
      of in-hospital mortality. The scoring system including sEPCR predicted mortality
      with an AUC of 0.75. CONCLUSIONS: Our findings confirm that high plasma sEPCR and
      its increase at D2 are associated with poor outcome in sepsis and thus we propose
      sEPCR as a key player in the pathogenesis of sepsis and as a potential biomarker
      of sepsis outcome.

PMID- 30290853
TI  - Innovative Method for the Analysis of Dexpanthenol in Hair Care Products.
AB  - Background: Dexpanthenol is a widely used humectant in hair care products,
      especially anti-hairfall products. The hair care industry is highly regulated in
      East Asia and treats products containing the combination of dexpanthenol, zinc
      pyrithione, and nicotinamide (vitamin B3) as quasi-drugs. Objective: Because
      dexpanthenol lacks a UV chromophore, existing methodologies for analysis in
      finished products include pretreatments and/or HPLC-UV analysis at low
      wavelengths at which poor signal-to-noise is observed. These time-consuming
      methods lack the robustness needed for routine use in quality laboratories. This
      has resulted in the need for a simple, fast, accurate, and robust UHPLC-MS method
      to quantify dexpanthenol in hair care products that could be easily adapted in
      quality laboratories. Methods: The MS detection was performed in positive ion
      mode with data acquired in single-ion recording for dexpanthenol (206.14 m/z),
      dexpanthenol-d6 (212.29 m/z), and Leucine Enkephalin acetate salt (556.28 m/z).
      Quantitation was performed using peak area ratio of dexpanthenol to the internal
      standard. Results: The resulting linear curve R2 was 0.9998 with sample precision
      RSDs <2.5%. The accuracy recoveries were within 2% and the robustness results
      were within 3% of the nominal conditions. Conclusions: The resulting method for
      the quantitation of dexpanthenol is fast, accurate, and robust in the range of
      170.24-1024.5 ng/mL in shampoo and conditioner, which is easily adaptable in
      quality laboratories. Highlights: This study determined optimal sample
      preparation and UHPLC-MS conditions to quantify dexpanthenol in finished hair
      care products.

PMID- 30290855
TI  - Use of Magnesium Silicate as a New Type of Adsorbent for Dispersive Solid-Phase
      Extraction Clean Up of the Quick, Cheap, Effective, Rugged, and Safe Method for
      Pesticides During Analysis of Lager Beer by Gas Chromatography-Tandem Mass
      Spectrometry.
AB  - Background: Pesticides are applied for pest control during the production of
      cereal grains used in beer production. Given the risks for consumers, it is
      important to analyze the pesticide residues. Objective: Quick, easy, cheap,
      effective, rugged, and safe (QuEChERS)-based methods are very effective, and
      improvement in the clean-up step is an important approach. Methods: Primary
      secondary amine (PSA) and magnesium silicate were evaluated for dispersive-solid
      phase extraction (d-SPE) clean-up step in extracts provided by the QuEChERS
      method in combination with GC-tandem MS for the determination of acetamiprid,
      terburfos, alachlor, ametryn, atrazine, azoxystrobin, carbofuran, carbosulfan,
      cypermethrin, deltamethrin, difenoconazole, esfenvalerate, flutriafol,
      thiamethoxam, and parathion-methyl in lager beer. Results: The amount of 50 mg of
      magnesium silicate was suitable for cleaning up beer extract as an alternative d
      SPE material to PSA. The method was validated using beer fortified with
      pesticides at three concentration levels (0.002, 0.01, and 0.1 MUg/mL). Average
      recoveries ranged from 70 to 123%, with RSDs between 0.3 and 10.5 %. Matrix
      effects were observed by comparing the slope of matrix-matched standard
      calibration with that of solvent. The method provided good linearity at the
      concentration levels of 0.001-2.5 MUg/mL. Detection limits ranged from 0.0001 to
      0.0007 MUg/mL and quantification limits ranged from 0.001 to 0.006 MUg/mL. The
      method was applied to nine beer brands. Conclusions: Results showed that
      magnesium silicate is an efficient alternative clean-up material to reduce
      analysis costs while maintaining the method reliability and accuracy. Highlights:
      Magnesium silicate was effective as adsorbent for d-SPE step in the analysis of
      pesticides in beer.

PMID- 30290856
TI  - Detection and Analysis of Xenobiotics in Food Products and Environmental and
      Biological Samples by High-Performance Chromatographic Techniques Coupled with
      High-Resolution Mass Spectrometry.

PMID- 30290857
TI  - Corrigendum to "Congenital myasthenic syndromes in Turkey: Clinical clues and
      prognosis with long term follow-up" [Neuromuscular Disorders 28/4 (2018) 315
      322].

PMID- 30290858
TI  - Nitrifiers activity and community characteristics under stress conditions in
      partial nitrification systems treating ammonium-rich wastewater.
AB  - Long-term exposure of nitrifiers to high concentrations of free ammonia (FA) and
      free nitrous acid (FNA) may affect nitrifiers activity and nitrous oxide (N2O)
      emission. Two sequencing batch reactors (SBRs) were operated at influent ammonium
      nitrogen (NH4-N) concentrations of 800mg/L (SBRH) and 335mg/L (SBRL),
      respectively. The NH4-N removal rates in SBRH and SBRL were around 2.4 and
      1.0g/L/day with the nitritation efficiencies of 99.3% and 95.7%, respectively. In
      the simulated SBR cycle, the N2O emission factors were 1.61% in SBRH and 2.30% in
      SBRL. N2O emission was affected slightly by FA with the emission factor of 0.22%
      0.65%, while N2O emission increased with increasing FNA concentrations with the
      emission factor of 0.22%-0.96%. The dominant ammonia oxidizing bacteria (AOB)
      were Nitrosomonas spp. in both reactors, and their relative proportions were
      38.89% in SBRH and 13.36% in SBRL. Within the AOB genus, a species (i.e.,
      operational taxonomic unit [OTU] 76) that was phylogenetically identical to
      Nitrosomonas europaea accounted for 99.07% and 82.04% in SBRH and SBRL,
      respectively. Additionally, OTU 215, which was related to Nitrosomonas stercoris,
      accounted for 16.77% of the AOB in SBRL.

PMID- 30290859
TI  - Strong enhancement of methylene blue removal from binary wastewater by in-situ
      ferrite process.
AB  - Dye wastewater containing heavy metal ions is a common industrial effluent with
      complex physicochemical properties. The treatment of metal-dye binary wastewater
      is difficult. In this work, a novel in-situ ferrite process (IFP) was applied to
      treat Methylene Blue (MB)-Cu(II) binary wastewater, and the operational
      parameters were optimized for MB removal. Results showed that the optimum
      operating conditions were OH/M of 1.72, Cu2+/Fe2+ ratio of 1/2.5, reaction time
      of 90min, aeration intensity of 320mL/min, and reaction temperature of 40 degrees
      C. Moreover, the presence of Ca2+ and Mg2+ moderately influenced the MB removal.
      Physical characterization results indicated that the precipitates yielded in IFP
      presented high surface area (232.50m2/g) and a multi-porous structure. Based on
      the Langmuir model, the maximum adsorption capacity toward MB was 347.82mg/g for
      the precipitates produced in IFP, which outperformed most other adsorbents.
      Furthermore, IFP rapidly sequestered MB with removal efficiency 5 to 10 times
      greater than that by general ferrite adsorption, which suggested a strong
      enhancement of MB removal by IFP. The MB removal process by IFP showed two
      different high removal stages, each with a corresponding removal mechanism. In
      the first brief stage (<5min), the initial high MB removal (~95%) was achieved by
      predominantly electrostatic interactions. Then the sweep effect and encapsulation
      were dominant in the second longer stage.

PMID- 30290860
TI  - The effects of hydrogen peroxide pre-oxidation on ultrafiltration membrane
      biofouling alleviation in drinking water treatment.
AB  - Pre-oxidation is widely used to reduce ultrafiltration membrane fouling. However,
      the variation in the composition of microbial communities and extracellular
      polymeric substances (EPSs) accompanying pre-oxidation in drinking water
      treatment has received little attention. In this study, hydrogen peroxide (H2O2)
      was used in a coagulation-ultrafiltration process with Al2(SO4)3.18H2O. A long
      term reactor experiment (60d) showed that pre-oxidation alleviated membrane
      fouling, mainly due to its inhibition of microbial growth, as observed by flow
      cytometry measurements of the membrane tank water. Further analysis of the formed
      cake layer demonstrated that the corresponding levels of EPS released from the
      microbes were lower with than without H2O2 treatment. In comparison to
      polysaccharides, proteins dominated the EPS. 2D-electrophoresis showed little
      difference (p>0.05, Student's t-test) in the composition of proteins in the cake
      layer between the treatments with and without H2O2. The molecular weights of
      proteins ranged from approximately 30-50kDa and the majority of isoelectric
      points ranged from 6 to 8. High-throughput sequencing showed that the predominant
      bacteria were Proteobacteria, Bacteroidetes, and Verrucomicrobia in both cake
      layers. However, the relative abundance of Planctomycetes was higher in the cake
      layer with H2O2 pre-oxidation, which was likely probably due to the strong
      oxidative resistance of its cell wall. Overall, our findings clarify the
      fundamental molecular mechanism in H2O2 pre-oxidation for ultrafiltration
      membrane bio-fouling alleviation in drinking water treatment.

PMID- 30290861
TI  - Influence of metal-contamination on distribution in subcellular fractions of the
      earthworm (Metaphire californica) from Hunan Province, China.
AB  - Earthworms have the ability to accumulate of heavy metals, however, there was few
      studies that addressed the metals in earthworm at subcellular levels in fields.
      The distributions of metals (Cd, Cu, Zn, and Pb) in subcellular fractions
      (cytosol, debris, and granules) of earthworm Metaphire californica were
      investigated. The relationship between soil metals and earthworms were analyzed
      to explain its high plasticity to inhabit in situ contaminated soil of Hunan
      Province, south China. The concentration of Cd in subcellular compartments showed
      the same pattern as Cu in the order of cytosol > debris > granules. The
      distribution of Zn and Pb in earthworms indicated a similar propensity for
      different subcellular fractions that ranked as granules > debris > cytosol for
      Zn, and granules > cytosol > debris for Pb. The internal metal concentrations in
      earthworms increased with the soil metals (p<0.05). Significant positive
      correlations were found between soil Cd and Cd concentrations in cytosol and
      debris (p<0.01). Moreover, the soil Pb concentration significantly influenced the
      Pb concentrations in cytosol and debris (p<0.01), similar to that of Cd. The soil
      Cu concentrations was only associated with the Cu in granules (p<0.05). Soil Zn
      concentrations correlated with the Zn concentrations in each subcellular fraction
      (p<0.05). Our results provide insights into the variations of metals partitioning
      in earthworms at subcellular levels and the relationships of soil metals, which
      could be one of the detoxification strategies to adapt the long-term contaminated
      environment.

PMID- 30290862
TI  - Enhanced photocatalytic activity of rGO/TiO2 for the decomposition of
      formaldehyde under visible light irradiation.
AB  - Due to the low concentration of indoor air contaminants, photocatalytic
      technology shows low efficiency for indoor air purification. The application of
      TiO2 for photocatalytic removal of formaldehyde is limited, because TiO2 can only
      absorb ultraviolet (UV) light. Immobilization of TiO2 nanoparticles on the
      surface of graphene can improve the visible light photocatalytic activity and the
      adsorption capacity. In this study, rGO (reduced graphene oxide)/TiO2 was
      synthesized through a hydrothermal method using titanium tetrabutoxide and
      graphene oxide as precursors, and was used for the degradation of low
      concentration formaldehyde in indoor air under visible light illumination.
      Characterization of the crystalline structure and morphology of rGO/TiO2 revealed
      that most GO was reduced to rGO during the hydrothermal treatment, and anatase
      TiO2 nanoparticles (with particle size of 15-30nm) were dispersed well on the
      surface of the rGO sheets. rGO/TiO2 exhibited excellent photocatalytic activity
      for degradation of formaldehyde in indoor air and this can be attributed to the
      role of rGO, which can act as the electron sink and transporter for separating
      photo-generated electron-hole pairs through interfacial charge transfer.
      Furthermore, rGO could adsorb formaldehyde molecules from air to produce a high
      concentration of formaldehyde on the surface of rGO/TiO2. Under visible light
      irradiation for 240min, the concentration of formaldehyde could be reduced to
      58.5ppbV. rGO/TiO2 showed excellent moisture-resistance behavior, and after five
      cycles, rGO/TiO2 maintained high photocatalytic activity for the removal of
      formaldehyde (84.6%). This work suggests that the synthesized rGO/TiO2 is a
      promising photocatalyst for indoor formaldehyde removal.

PMID- 30290863
TI  - Exposure to air pollutants in Vietnam: Assessing potential risk for tourists.
AB  - Tourism can form an important component of a nation's GDP, and Vietnam is among
      the most visited countries in Southeast Asia. Most studies on personal exposure
      focus on the general population, or occupational cohorts with exposure to
      specific pollutants. However, short-term exposure to air pollutants while
      visiting regions with high levels of air pollution can lead to acute health
      effects. A personal exposure study was conducted across three cities in Vietnam
      to estimate exposure to particulate matter (PM2.5) and black carbon for tourists.
      Measurements were conducted during the wet season in 2014 in Ho Chi Minh City, Da
      Lat and Nha Trang using portable instrumentation. Average 24-hr PM2.5 and BC
      exposures were estimated as 18.9+/-9.24 and 3.41+/-1.33MUg/m3 and among the three
      cities, Ho Chi Minh was found to have the highest PM2.5 concentrations.
      Environmental tobacco smoke, commuting and street food stands were found to
      contribute to highest levels of exposure to PM2.5 and BC across all cities.

PMID- 30290864
TI  - Alkali resistance promotion of Ce-doped vanadium-titanic-based NH3-SCR catalysts.
AB  - The effect of K deactivation on V2O5/WO3-TiO2 and Ce-doped V2O5/WO3-TiO2
      catalysts in the selective catalytic reduction (SCR) of NOx by NH3 was studied.
      Ce-doped V2O5/WO3-TiO2 showed significantly higher resistance to K deactivation
      than V2O5/WO3-TiO2. Ce-doped V2O5/WO3-TiO2 with K/V=4 (molar ratio) showed 90%
      NOx conversion at 350 degrees C, whereas in this case V2O5/WO3-TiO2 showed no
      activity. The fresh and K-poisoned V2O5/WO3-TiO2 and Ce-doped V2O5/WO3-TiO2
      catalysts were investigated by means of in situ diffuse reflectance infrared
      Fourier transform spectroscopy (DRIFTS), NH3-temperature progress decomposition
      (NH3-TPD), X-ray photoelectron spectroscopy (XPS) and H2-temperature program
      reduction (H2-TPR). The effect of Ce doping on the improving resistance to K of
      V2O5/WO3-TiO2were discussed.

PMID- 30290865
TI  - Effect of biochar on fate and transport of manure-borne estrogens in sandy soil.
AB  - The feasibility of using two types of biochars to reduce steroid hormone
      pollution from poultry and swine manure application on agricultural land was
      evaluated. The sorption affinity and desorption resistance of softwood and
      hardwood biochars were also determined for two estrogen hormones, 17beta
      estradiol (E2) and its primary metabolite estrone (E1). The softwood and hardwood
      biochars demonstrated high retention capacity for both estrogens. The effective
      distribution coefficient (Kdeff) of soil-softwood-derived biochar (SBS450) was
      significantly higher than soil-hardwood-derived biochar (SBH750), indicating the
      stronger sorption affinity of SBS450 for estrogens. To validate the laboratory
      results, a field lysimeter experiment was conducted to study the fate and
      transport of E2 and E1 in soil and leachate in the presence of 1% softwood
      biochar (BS450) in topsoil and to compare it with soil without any amendments.
      The spatio-temporal distribution of both estrogens was monitored at four depths
      over a 46-day period. The lysimeters, in which the surface layer of soil was
      amended with biochar, retained significantly higher concentrations of both
      estrogen hormones. Although they leached through the soil and were detected in
      leachates, collected at 1.0m depth, the concentrations were significantly lower
      in the leachate collected from biochar-amended lysimeters. The result confirmed
      the efficacy of biochar amendment as a remediation technique to alleviate the
      manure-borne hormonal pollution of groundwater.

PMID- 30290866
TI  - High mercury leachate containing HgS22- complex ion: Detoxifying solidification
      and high efficiency Hg extraction.
AB  - Clean and efficient treatment of high-mercury leachate produced from remediation
      of mercury-polluted soil has become a huge challenge for environmental
      scientists. In this work, cement solidification was firstly adopted to treat the
      high-concentration mercury leachate, which had high alkalinity. Different mercury
      concentrations, namely 3.120mg/L Hg mercury leachate and 9.243mg/L Hg mercury
      concentrated leachate, were separately solidified by Portland cement. The results
      indicated that simply using the cement can properly solidify both the leachates
      to meet the waste landfill standard, with liquid (mL)/solid (g) ratio (L/S ratio)
      of 4:10-6:10. In order to make full use of mercury in the leachates, a Hg
      extraction method was subsequently carried out under different experimental
      parameters, such as temperature and pH value. It was shown that the Hg extraction
      ratio could reach as high as 99.84% and almost all the mercury in the leachate
      could be transformed to HgS precipitate; moreover, the Hg concentration in the
      treated leachate was reduced from 3.120 to 0.005mg/L at pH2.98 and 30 degrees C,
      which was much less than the limit of the national standard, indicating that the
      leachate had been completely cleaned and could be discharged freely. Hence,
      simple cement solidification renders high-mercury leachate nontoxic, and the Hg
      extraction method can successfully recover the Hg and enable the residual
      leachate to be discharged safely.

PMID- 30290867
TI  - Facile one-step synthesis of functionalized biochar from sustainable prolifera
      green-tide source for enhanced adsorption of copper ions.
AB  - The use of biochars formed by hydrothermal carbonization for the treatment of
      contaminated water has been greatly limited, due to their poorly developed
      porosity and low content of surface functional groups. Also, the most common
      modification routes inevitably require post-treatment processes, which are time
      consuming and energy-wasting. Hence, the objective of this research was to
      produce a cost-effective biochar with improved performance for the treatment of
      heavy metal pollution through a facile one-step hydrothermal carbonization
      process coupled with ammonium phosphate, thiocarbamide, ammonium chloride or
      urea, without any post-treatment. The effects of various operational parameters,
      including type of modification reagent, time and temperature of hydrothermal
      treatment, and ratio of modification reagent to precursor during impregnation, on
      the copper ion adsorption were examined. The adsorption data fit the Langmuir
      adsorption isotherm model quite well. The maximum adsorption capacities (mg/g) of
      the biochars towards copper ions followed the order of 40-8h-1.0-APBC (95.24)>140
      8h-0-BC (12.52)>140-8h-1.0-TUBC (12.08)>140-8h-1.0-ACBC (7.440)>140-8h-1.0-URBC
      (5.277). The results indicated that biochars modified with ammonium phosphate
      displayed excellent adsorption performance toward copper ions, which was 7.6-fold
      higher than that of the pristine biochar. EDX and FT-IR analyses before and after
      adsorption demonstrated that the main removal mechanism involved complexation
      between the phosphate groups on the surface of the modified biochars and copper
      ions.

PMID- 30290868
TI  - Study of ciprofloxacin removal by biochar obtained from used tea leaves.
AB  - In this study, used tea leaves (UTLs) were pyrolyzed to obtain used tea-leaf
      biochar (UTC), and then the UTC was used as an adsorbent to remove ciprofloxacin
      (CIP) from aqueous solutions. Batch experiments were conducted to investigate the
      CIP adsorption performance and mechanism. The results showed that the CIP
      adsorbing ability first increased and then declined as the UTC pyrolysis
      temperature increased. The UTC obtained at 450 degrees C presented excellent CIP
      absorbing ability at pH6 and 40 degrees C. The maximum monolayer adsorption
      capacity was 238.10mg/g based on the Langmuir isotherm model. The pseudo-second
      order kinetic equation agreed well with the CIP adsorption process, which was
      controlled by both external boundary layer diffusion and intra-particle
      diffusion. The characterization analysis revealed that the OH groups, CC bonds of
      aromatic rings, CH groups in aromatic rings and phenolic CO bonds play vital
      roles in the CIP adsorption process, and that the NC, NO, OCO and COH groups of
      UTC were consumed in large quantities. pi-pi interactions, hydrogen bonding and
      electrostatic attraction are inferred as the main adsorption mechanisms. The
      present work provides not only a feasible and promising approach for UTLs
      utilization but also a potential adsorbent material for removing high
      concentrations of CIP from aqueous solutions.

PMID- 30290869
TI  - Oxidation of antimony (III) in soil by manganese (IV) oxide using X-ray
      absorption fine structure.
AB  - The oxidation of antimony (III) in soils was studied using X-ray absorption fine
      structure (XAFS) spectra. An andosol soil sample and artificial soil samples
      (SiO2 blended with iron (III) hydroxide and manganese (IV) oxide) were used
      herein. After adding antimony (III) oxide to all soil samples, the oxidation
      process was observed by recording the XAFS spectra of Sb K-edge, Fe K-edge, and
      Mn K-edge. The results indicated that manganese (IV) oxide played an important
      role in the oxidation of Sb(III); however iron (III) hydroxide was not directly
      related to the reaction. During a 2-hr continuous Sb K-edge X-ray absorption near
      edge structure (XANES) measurement with an interval of 1min of one of the
      artificial soil samples (SiO2+MnO2+Sb2O3), a pseudo-first-order reaction was
      determined with an average estimated rate of 0.52+/-0.04hr-1. Compared to the
      lower oxidation rate of andosol, it is suggested that because of the low
      concentration of Mn(IV) in natural soils, the oxidation process of Sb(III) might
      be relatively slow and require more time to convert Sb(III) to Sb(V).

PMID- 30290870
TI  - Effects of O3/Cl2 disinfection on corrosion and opportunistic pathogens growth in
      drinking water distribution systems.
AB  - The effects of O3/Cl2 disinfection on corrosion and the growth of opportunistic
      pathogens in drinking water distribution systems were studied using annular
      reactors (ARs). The corrosion process and most probable number (MPN) analysis
      indicated that the higher content of iron-oxidizing bacteria and iron-reducing
      bacteria in biofilms of the AR treated with O3/Cl2 induced higher Fe3O4 formation
      in corrosion scales. These corrosion scales became more stable than the ones that
      formed in the AR treated with Cl2 alone. O3/Cl2 disinfection inhibited corrosion
      and iron release efficiently by changing the content of corrosion-related
      bacteria. Moreover, ozone disinfection inactivated or damaged the opportunistic
      pathogens due to its strong oxidizing properties. The damaged bacteria resulting
      from initial ozone treatment were inactivated by the subsequent chlorine
      disinfection. Compared with the AR treated with Cl2 alone, the opportunistic
      pathogens M. avium and L. pneumophila were not detectable in effluents of the AR
      treated with O3/Cl2, and decreased to (4.60+/-0.14) and (3.09+/-0.12) log10 (gene
      copies/g corrosion scales) in biofilms, respectively. The amoeba counts were also
      lower in the AR treated with O3/Cl2. Therefore, O3/Cl2 disinfection can
      effectively control opportunistic pathogens in effluents and biofilms of an AR
      used as a model for a drinking water distribution system.

PMID- 30290871
TI  - A green method to synthesize flowerlike Fe(OH)3 microspheres for enhanced
      adsorption performance toward organic and heavy metal pollutants.
AB  - Dyestuffs and heavy metal ions in water are seriously harmful to the ecological
      environment and human health. Three-dimensional (3D) flowerlike Fe(OH)3
      microspheres were synthesized through a green yet low-cost injection method, for
      the removal of organic dyes and heavy metal ions. The Fe(OH)3 microspheres were
      characterized by thermal gravimetric analysis (TGA), Fourier transform infrared
      (FT-IR), and transmission electron microscopy (TEM) techniques. The adsorption
      kinetics of Congo Red (CR) on Fe(OH)3 microspheres obeyed the pseudo-second-order
      model. Cr6+ and Pb2+ adsorption behaviors on Fe(OH)3 microspheres followed the
      Langmuir isotherm model. The maximum adsorption capacities of the synthesized
      Fe(OH)3 were 308, 52.94, and 75.64mg/g for CR, Cr6+, and Pb2+ respectively. The
      enhanced adsorption performance originated from its surface properties and large
      specific surface area of 250m2/g. The microspheres also have excellent adsorption
      stability and recyclability. Another merit of the Fe(OH)3 material is that it
      also acts as a Fenton-like catalyst. These twin functionalities (both as
      adsorbent and Fenton-like catalyst) give the synthesized Fe(OH)3 microspheres
      great potential in the field of water treatment.

PMID- 30290872
TI  - Effect of lanthanum loading on nanosized CeO2-ZnO solid catalysts supported on
      cordierite for diesel soot oxidation.
AB  - We report the application of a solid lanthanum-ceria-zinc catalyst in the
      catalytic regeneration of diesel particulate filters (DPF) in diesel engines. We
      synthesized a CeO2-ZnO-La2O3 (Ce-Zn-La) mixed oxide by a lactic acid-mediated sol
      gel method, which efficiently coated cordierite substrates for soot capture and
      combustion. We studied the effects of La loading on the physicochemical and
      catalytic properties of Ce-Zn mixed oxide during low-temperature soot combustion
      processes. We characterized the synthesized catalysts by X-ray diffraction (XRD),
      Fourier-transform infrared spectroscopy (FTIR), N2 adsorption, Raman
      spectroscopy, oxygen storage capacity (OSC), and scanning and transmission
      electron microscopy (SEM and TEM). Thermogravimetric and differential thermal
      analysis (TGA/DTA) confirmed that the catalysts effectively reduced the soot
      oxidation temperature. The ternary Ce-Zn-La mixed oxide catalyst with Ce/Zn/La
      atomic ratio of 2:1:0.5 had the highest catalytic activity and promoted soot
      oxidation at temperatures below 390 degrees C. This indicated that the large
      number of oxygen vacancies in the catalyst structure generated oxygen species at
      low temperatures. Raman spectroscopy measurements revealed the presence of oxygen
      vacancies and lattice defects in Ce-Zn-La samples, which were key parameters
      concerning the stability and redox properties of the prepared catalysts.

PMID- 30290873
TI  - Size-resolved effective density of submicron particles during summertime in the
      rural atmosphere of Beijing, China.
AB  - Particle density is an important physical property of atmospheric particles. The
      information on high time-resolution size-resolved particle density is essential
      for understanding the atmospheric physical and chemical aging processes of
      aerosols particles. In the present study, a centrifugal particle mass analyzer
      (CPMA) combined with a differential mobility analyzer (DMA) was deployed to
      determine the size-resolved effective density of 50 to 350nm particles at a rural
      site of Beijing during summer 2016. The measured particle effective densities
      decreased with increasing particle sizes and ranged from 1.43 to 1.55g/cm3, on
      average. The effective particle density distributions were dominated by a mode
      peaked at around 1.5g/cm3 for 50 to 350nm particles. Extra modes with peaks at
      1.0, 0.8, and 0.6g/cm3 for 150, 240, and 350nm particles, which might be freshly
      emitted soot particles, were observed during intensive primary emissions
      episodes. The particle effective densities showed a diurnal variation pattern,
      with higher values during daytime. A case study showed that the effective density
      of Aitken mode particles during the new particle formation (NPF) event decreased
      considerably, indicating the significant contribution of organics to new particle
      growth.

PMID- 30290874
TI  - Toxicity assessment and histopathological analysis of nano-ZnO against marine
      fish (Mugilogobius chulae) embryos.
AB  - The toxicity of nano-materials has received increasing attention in recent years.
      Nevertheless, relatively few studies have focused on their oceanic distributions
      and toxicities. In this study, we assessed nano-ZnO toxicity in marine organisms
      using the yellowstriped goby (Mugilogobius chulae). The relative differences in
      nano-ZnO dissolution and dispersal in seawater and fresh water were also
      investigated. The effects of nano-ZnO on embryonic development, deformity,
      hatching, mortality, and histopathology were analyzed. In addition, the effects
      of the Zn2+ concentration on M. chulae hatching and mortality were compared. The
      results showed that nano-ZnO had higher solubility in seawater than in fresh
      water. Nano-ZnO significantly inhibited hatching. By the fifth day of exposure,
      the LC50 of nano-ZnO was 45.40mg/L, and the mortality rate spiked. Hatching
      inhibition and lethality were dose-dependent over a range of 1-25mg/L nano-ZnO.
      Zn2+ inhibited hatching and increased lethality, but its effects were weaker than
      those of nano-ZnO at the same concentrations. Nano-ZnO also induced spinal
      bending, oedema, hypoplasia, and other deformities in M. chulae embryos and
      larvae. Histopathology revealed vacuolar degeneration, hepatocyte and enterocyte
      enlargement, and morphological abnormalities of the vertebrae. Therefore, nano
      ZnO caused malformations in M. chulae by affecting embryonic growth and
      development. We conclude that nano-ZnO toxicity in seawater was significantly
      positively correlated with the associated Zn2+ concentration and sedimentary
      behaviour. The toxicity of nano-ZnO was cumulative and showed a critical point,
      beyond which embryonic and developmental toxicity in marine fish was observed.

PMID- 30290875
TI  - Degradation of sulfonamides and formation of trihalomethanes by chlorination
      after pre-oxidation with Fe(VI).
AB  - Sulfonamides are used in human therapy, animal husbandry and agriculture but are
      not easily biodegradable, and are often detected in surface water. Sulfamethazine
      (SMZ) and sulfadiazine (SDZ) are two widely used sulfonamide antibiotics that are
      used heavily in agriculture. In this study, they were degraded in an aqueous
      system by chlorination after pre-oxidation with ferrate(VI) (FeVIO42-, Fe(VI)),
      an environmentally friendly oxidation technique that has been shown to be
      effective in degrading various organics. The kinetics of the degradation were
      determined as a function of Fe(VI) (0-1.5mg/L), free chlorine (0-1.8mg/L) and
      temperature (15-35 degrees C). According to the experimental results, SMZ
      chlorination followed second-order kinetics with increasing Fe(VI) dosage, and
      the effect of the initial free chlorine concentration on the reaction kinetics
      with pre-oxidation by Fe(VI) fitted a pseudo-first order model. The rate
      constants of SDZ and SMZ chlorination at different temperatures were related to
      the Arrhenius equation. Fe(VI) could reduce the levels of THMs formed and the
      toxicity of the sulfonamide degradation systems with Fe(VI) doses of 0.5-1.5mg/L,
      which provides a reference for ensuring water quality in drinking water systems.

PMID- 30290876
TI  - Destratification and oxygenation efficiency of a water-lifting aerator system in
      a deep reservoir: Implications for optimal operation.
AB  - Thermal stratification is a common phenomenon in lakes and reservoirs and has a
      significant influence on water quality dynamics. Heihe Reservoir is a canyon
      shaped reservoir in Shaanxi Province with strong thermal stratification.
      Therefore, eight water-lifting aerators (WLAs) were installed in this reservoir,
      which could overcome thermal stratification and increase oxygenation with gas
      flows between 20 and 50m3/hr, and oxygenate the hypolimnion with gas flows less
      than 20m3/hr. To examine the destratification efficiency of the WLA system, we
      used a three-dimensional hydrodynamic module based on MIKE 3 to simulate the
      thermal structure of Heihe Reservoir and compared the simulations with measured
      data. Results showed that operation of the WLA system promoted water mixing and
      effectively oxygenated the hypolimnion. Through the established energy
      utilization assessment method, the energy utilization efficiency of the WLA
      system was between 5.36% and 7.30%, indicating the capability of the technique
      for destratification in such a large reservoir. When the surface water
      temperature dropped to the theoretical mixed water temperature calculated by the
      energy utilization assessment method, reducing gas flow could save energy. This
      would prevent anaerobic conditions from occurring in the bottom water and
      maintain good water quality in Heihe Reservoir.

PMID- 30290878
TI  - Proarrhythmia and death with antiarrhythmic drugs for atrial fibrillation, and
      the unfulfilled promise of comparative effectiveness research.

PMID- 30290879
TI  - Moderate-to-high levels of satisfaction and no important concerns in patients who
      received treatment with clear orthodontic aligners.

PMID- 30290877
TI  - Reduced graphene oxide-nano zero value iron (rGO-nZVI) micro-electrolysis
      accelerating Cr(VI) removal in aquifer.
AB  - Nanoscale zero-valent iron (nZVI) assembled on graphene oxide (GO) (rGO-nZVI)
      composites were synthesized by reduction of GO and ferrous ions with potassium
      borohydride, for use in Cr(VI) removal from aqueous solution. The results showed
      that the two-dimensional structure of GO could provide a skeleton support for
      Fe0, thus overcoming the bottleneck of aggregation for nZVI. Also, rGO-nZVI would
      form a ferric-carbon micro-electrolysis system in Cr(VI)-contaminated aquifers,
      enhancing and accelerating electron transfer, exhibiting high rate and capacity
      for Cr(VI) removal. The optimum dosage of the applied rGO-nZVI was linearly
      correlated with the initial Cr(VI) concentration. Characterization of rGO-nZVI
      before and after reaction with Cr(VI) revealed the process of Cr(VI) removal: rGO
      nZVI firstly transferred electrons from Fe0 cores via their Fe(II)/Fe(III) shells
      to the GO sheet; there, negatively charged Cr(VI) received electrons and changed
      into positively charged Cr(III), which was adsorbed by the negatively charged GO
      sheet, avoiding the capping and passivating of nZVI. rGO-nZVI formed a good
      electrically conductive network, and thus had long-term electron releasing
      properties, which was important for groundwater remediation.

PMID- 30290880
TI  - Coronectomy seems to result in low nerve injury rate in the long term.

PMID- 30290881
TI  - Prevalence and Prognostic Significance of Right Ventricular Dysfunction in
      Patients With Hypertrophic Cardiomyopathy.
AB  - Few data are available regarding the prevalence and clinical significance of
      right ventricular systolic dysfunction (RVSD) in hypertrophic cardiomyopathy (HC)
      patients. This study aimed to evaluate right ventricular (RV) systolic function
      by cardiovascular magnetic resonance and explore the prevalence and prognostic
      significance of RVSD in HC patients. A total of 226 patients with HC assessed by
      cardiovascular magnetic resonance were included in this retrospective study. RVSD
      was defined by RV ejection fraction (RVEF) <=45% and was present in 26 (11.5%)
      patients. Association between RVSD, clinical characteristics, and outcomes were
      analyzed. RVEF was significantly lower in patients with RVSD than without RVSD
      (36.2 +/- 7.0% vs 60.5 +/- 7.4%, p < 0.001). There was a positive correlation
      between RVEF and left ventricular ejection fraction (r = 0.45; p < 0.001). During
      a mean follow-up of 30.5 +/- 23.9 months, there were 22 (9.7 %) all-cause
      mortality, including 12 (5.3%) cardiovascular death. Kaplan-Meier analysis showed
      a significantly higher risk for cardiovascular mortality in patients with RVSD (p
      = 0.026), but no significant difference in all-cause mortality (p = 0.118) and
      heart failure related rehospitalization (p = 0.485). On multivariate Cox
      regression analysis, RVSD (hazard ratio 5.36; confidence interval 1.39 to 20.77;
      p = 0.015) and RVEF (hazard ratio 0.94; confidence interval 0.89 to 0.98; p =
      0.011) were independent predictors of cardiovascular mortality. In conclusion,
      RVSD is a common phenotype and a strong independent predictor of cardiovascular
      mortality in HC patients.

PMID- 30290883
TI  - Calcitriol increases nitric oxide production and modulates microbicidal capacity
      against Mycobacterium bovis in bovine macrophages.
AB  - Bovine tuberculosis, a re-emerging infectious disease caused by Mycobacterium
      bovis, can be transmitted to humans. Global prevalence of M. bovis in humans is
      underestimated and represents a serious public health risk in developing
      countries. In light of this situation, it is important to note that our
      understanding of the immunopathogenesis of human tuberculosis can be improved by
      studying this disease in the bovine model. Stimulation of the bovine innate
      immune system with calcitriol (1,25(OH)2D3) leads to an increase in bactericidal
      molecules involved in macrophage antimicrobial activity. It is unknown, however,
      if calcitriol's effect on bovine macrophages impacts intracellular bacterial
      replication. With these considerations in mind, this study sought to investigate
      the specific role of calcitriol in tuberculosis control in bovine macrophages, in
      the hopes of uncovering information applicable to human tuberculosis. As such,
      infection with M. bovis was shown to induce expression of CYP27B1 and VDR genes
      in macrophages. Moreover, addition of 1,25(OH)2D3 to cultures of macrophages
      previously infected with mycobacteria and/or activated by LPS triggered cellular
      expression of nitric oxide synthase (NOS2) and increased nitrite concentrations,
      both indicators of nitric oxide (NO) production. By means of a microbicidal
      assay, addition of 1,25(OH)2D3 was seen to increase macrophage phagocytosis and
      to decrease mycobacterial intracellular replication. Thus, taken together, our
      results show that calcitriol can help stimulate the innate immune system of
      bovines by increasing phagocytosis and decreasing intracellular replication of
      microorganisms, such as M. bovis, in macrophages, through the VDR pathway.

PMID- 30290882
TI  - Comparison of a new in-house HIV-1 TaqMan real-time PCR and three commercial HIV
      1 RNA quantitative assays.
AB  - OBJECTIVES: The aim of this study was to compare the analytical performance of an
      In-House HIV-1 viral load determination technique with three commercial kits
      including COBAS(r) AmpliPrep, RealStar(r), and RTA(r) HIV-1 Real-Time PCR.
      RESULTS: A total of 100 HIV-1 suspicious plasma samples were tested by the In
      House TaqMan(r) Real-Time PCR assay along with the above-mentioned kits.
      Comparative analysis between In-House and reference method (COBAS(r)
      AmpliPrep/COBAS(r) TaqMan(r) HIV-1 Test version 2.0) showed high concordance with
      a mean difference of 0.08 log10 copies/ml. All samples results were within -0.16
      0.31 log10 copies/ml. A suitable correlation was obtained with a coefficient (R2)
      of 0.82 between the In-House assay and RTA(r) Kit, however, two positive samples
      were not detected. The lowest agreement was detected with RealStar(r) HIV Kit 1.0
      (R2 = 0.49, r = 0.7). CONCLUSIONS: The newly developed method has suitable
      sensitivity, accuracy, and precision. In addition, it is cost-effective and can
      be an alternative in all laboratories.

PMID- 30290884
TI  - Fine mapping epitope on glycoprotein-Gn from Crimean-Congo hemorrhagic fever
      virus.
AB  - Glycoprotein (GP) is a major antigen of Crimean-Congo hemorrhagic fever virus
      (CCHFV), and binds to its receptor on the host cell and induces protective
      immunity in the host. The aim of this study is to identify all linear B cell
      epitopes (BCEs) on the N-terminal glycoprotein (Gn) of CCHFV using a modified
      overlapping peptide biosynthesis method. The eight fine BCEs (Gn-E1a,
      543RTQLV547; E1b, 553EIH555; E1c, 554IHEDSY559; E1d, 557DSYG560; E2,
      615CKQGFC620; E3a, 657GDILVD662; E3b, 662DCSGGQQH669, and E4, 678LGCPNVPL685)
      were identified using the rabbit antisera, which all were recognized by serum
      from IgG-positive sheep CCHFV-infected naturally in Western blotting. The
      multiple sequence alignment (MSA) revealed high conservation of the identified
      BCEs among ten CCHFV strains from different areas. These mapped epitopes of the
      CCHFV Gn would provide a basis for further the elucidation of CCHFV pathogenesis,
      and the development of CCHFV multi-epitope vaccines and detection reagents.

PMID- 30290885
TI  - Vaccination against Toxoplasma gondii using rhoptry antigens: a systematic
      review.
AB  - Toxoplasma gondii is an obligate intracellular parasitic protozoan that infects a
      wide variety of vertebrates as intermediate hosts. The aim of the current
      systematic review study is to clarify the latest status of studies in the
      literature regarding rhoptry-associated recombinant proteins or rhoptry
      associated recombinant DNAs as potential vaccines against toxoplasmosis. The
      search was performed systematically in 8 databases, four in English and four in
      Persian, up to February 2017. Overall, ROP2 was the most commonly used ROPs in
      DNA vaccines (27.27%) and protein vaccines (6.81%). Furthermore, regarding the
      type of adjuvants, route and dose of vaccination, animal models, challenge
      methods, and measurement of immune responses has been discussed in the text. It
      is hoped that this article help researchers to conduct more effective studies in
      the field of immunization against T. gondii.

PMID- 30290886
TI  - Clostridioides difficile in the environment, food, animals and humans in southern
      Italy: Occurrence and genetic relatedness.
AB  - One hundred and thirty-eight C. difficile isolates from different sources (66
      from the environment, 36 from animals, 9 from food and 27 from humans) were
      ribotyped by capillary electrophoresis PCR ribotyping (CE-PCR). A multilocus
      variable tandem repeat analysis (MLVA) was carried out on a sample subset. The
      most frequently isolated PCR ribotypes were 126 (15.9%), 078 (14.5%), 011/018
      (11.6%), 014/020/077 (10.1%), and 010 (2.8%). In particular, strains of PCR
      ribotype 011/018 were isolated from human, raw milk and environmental samples.
      The hypervirulent PCR ribotype 027 was isolated from two human samples. The
      majority of the strains were toxigenic (34.1% showed the toxigenic profile
      A+B+CDT+ and 38.9% the profile A+B+CDT-). MLVA allowed to identify 4 clonal
      complexes of genetically related isolates: complex n. 1 grouped together human,
      environmental and food strains, whereas complex n. 3 included human and
      environmental isolates. The use of MLVA gave further evidence to the possible
      role of environment, animals and food as routes of transmission of C. difficile
      infections to human.

PMID- 30290887
TI  - Genetic diversity and prevalence of piroplasm species in equids from Turkey.
AB  - Equine piroplasmosis (EP) is a protozoon disease caused by Babesia caballi and
      Theileria equi transmitted by ticks from the Ixodidae family. This study
      investigated the genetic heterogeneity and diversity of piroplasm genotypes using
      the Reverse Line Blotting (RLB) technique for piroplasm species in equids in
      Turkey. A total of 233 blood samples from 142 horses and 91 donkeys were
      collected in Sanliurfa, Tunceli, and Igdir. The RLB assay was performed for
      simultaneous detection of piroplasm species. The prevalence of piroplasm
      infection was 33.5% (95% CI; 27.4-39.9). T. equi was the most common species
      (%20.2; 95% CI 15.2-25.9), whereas B. caballi infection was not detected. Nine
      samples hybridized to the Theileria/Babesia and Theileria catch-all probes but
      did not hybridize to any species-specific probe tested, suggesting the presence
      of unrecognized Theileria variants or genotypes. Nine samples that gave Theileria
      spp. signal and two samples that gave T. equi specific signal were sent for
      sequence analysis and the A and D genotypes of T. equi were found. In addition,
      T. annulata, B. ovis, and B. canis species were detected in the samples and
      verified by sequence analysis in Turkey. More research is needed to understand
      the clinical impact of atypical piroplasm infections in equids.

PMID- 30290889
TI  - Immune response biomarkers in human and veterinary research.
AB  - Biomarkers are increasingly utilised in biological research and clinical practice
      for diagnosis of disease, monitoring of therapeutic prognosis, or as end points
      in clinical studies. Cytokines are small molecules that orchestrate immune
      responses and as such have great potential as biomarkers for both human and
      veterinary fields. Given the ease of sampling in the blood, and their high
      prevalence in clinical applications we will focus on protein detection as an area
      for biomarker discovery. This is facilitated by new technological developments
      such as digital ELISA that have led to significant increases in sensitivity. Two
      highly relevant examples include type I interferons, namely IFNalpha, that is now
      directly quantifiable by digital ELISA from biological samples. The application
      of this approach to the study of the unique bat interferon response may reveal
      novel findings with applications in both human and veterinary research. As a
      second example we will describe the use of CXCL10 as a disease biomarker in
      Tuberculosis, highlighting findings from human and mouse studies that should be
      considered in veterinary research. In summary, we describe how cytokines may be
      applied as novel biomarkers and illustrate two key examples where human and
      veterinary research may complement each other in line with the One Health
      objectives.

PMID- 30290888
TI  - Quantification of Toxoplasma gondii in the tissues of BALB/c mice after
      immunization with nanoliposomal excretory-secretory antigens using Real-Time PCR.
AB  - BACKGROUND: Toxoplasmosis is an infectious disease caused by the intracellular
      parasite Toxoplasma gondii. Although almost 1/3 of the world's population are
      seropositive, there is no effective vaccine against toxoplasmosis. Therefore, the
      development of an effective vaccine for control of toxoplasmosis is one of major
      concerns in parasitology. The aim of this study was to evaluate the efficacy of
      nano-liposomal excretory-secretory antigens (NLESA) in BALB/c mice. MATERIALS AND
      METHODS: Excretory-secretory antigens (ESA) was obtained from tachyzoites,
      encapsulated in the liposome and studied by scanning electron microscope. BALB/c
      mice were immunized with NLESA and ESA, sterile phosphate-buffered saline (PBS).
      Immunization was performed three times at 14-day intervals and challenged with 1
      * 104 tachyzoites of T. gondii RH strain four weeks later. The parasite load of
      mice blood, brain and spleen tissues were determined using quantitative PCR
      targeted at the repeated element (RE) gene. RESULTS: The immunization with NLESA
      and ESA induced a significant increase of anti-Toxoplasma IgG antibody compared
      with PBS group (P < 0.05). After challenge with tachyzoites, qPCR analyses showed
      significant reduction of parasite load in NLESA and ESA immunized mice compared
      with control group (P < 0.05). Also, NLESAs were more effective than ESAs and
      showed significantly reduced parasite load in blood (P = 0.001) and brain tissue
      (P = 0.01). DISCUSSION: The vaccination with NLESA showed more promising results
      comparing to ESA. Further studies are recommended in order to achieve
      effectiveness of the vaccine against T. gondii.

PMID- 30290891
TI  - The challenge of choosing the correct biologic for the correct asthma patient.

PMID- 30290890
TI  - Pentraxin 3 is up-regulated in epithelial mammary cells during Staphylococcus
      aureus intra-mammary infection in goat.
AB  - Pentraxin 3 is the prototypic long pentraxin and is produced by different cell
      populations (dendritic cells, monocytes/macrophages, endothelial cells, and
      fibroblasts) after pro-inflammatory stimulation. Different studies demonstrated
      the up-regulation of PTX3 during mastitis in ruminants, but its role is still
      unknown. We first investigated the conservation of PTX3 sequence among different
      species and its pattern of expression in a wide panel of organs from healthy
      goats. We studied the modulation of PTX3 during natural and experimental mammary
      infection, comparing its expression in blood, milk and mammary tissues from
      healthy and Staphylococcus aureus infected animals. We confirmed the high
      conservation of the molecule among different species. Goat PTX3 was expressed at
      high levels in bone marrow, mammary gland, aorta, rectum, pancreas, skin and
      lungs. PTX3 was up-regulated in epithelial mammary cells and in milk cells after
      S. aureus infection, suggesting that it represents a first line of defense in
      goat udder.

PMID- 30290892
TI  - Pediatric bronchial hyperresponsiveness and asthma phenotypes.

PMID- 30290893
TI  - In vitro allergy testing: Where are we now?

PMID- 30290894
TI  - Management of food allergies and asthma in schools.

PMID- 30290895
TI  - Occupational exposure to furry animals and asthma: The complex interconnection
      between work and everyday life.

PMID- 30290896
TI  - Authors' response.

PMID- 30290897
TI  - Beta-thalassaemia: all roads lead to a cure?

PMID- 30290898
TI  - Brentuximab vedotin for lymphoma in paediatric patients.

PMID- 30290899
TI  - An unmet need for long-term follow-up in Hodgkin's lymphoma?

PMID- 30290900
TI  - Immunoglobulin therapy and passive transfer of anti-HBc: too often forgotten.

PMID- 30290901
TI  - Thalidomide for myeloma: still here?

PMID- 30290902
TI  - Brentuximab vedotin for paediatric relapsed or refractory Hodgkin's lymphoma and
      anaplastic large-cell lymphoma: a multicentre, open-label, phase 1/2 study.
AB  - BACKGROUND: Despite remarkable progress in the treatment of newly-diagnosed
      classical Hodgkin's lymphoma and systemic anaplastic large-cell lymphoma,
      treatment of relapsed or refractory disease remains challenging. The aims of this
      study were to assess the safety, tolerability, recommended phase 2 dose, and
      efficacy of brentuximab vedotin in paediatric patients with relapsed or
      refractory Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma.
      METHODS: This open-label, dose-escalation phase 1/2 study was done at 12 centres
      across eight countries (France, Germany, Italy, Mexico, The Netherlands, Spain,
      UK, and USA). We recruited paediatric patients aged 7-18 years with relapsed or
      refractory classical Hodgkin's lymphoma or systemic anaplastic large-cell
      lymphoma, for whom standard treatment was unavailable or no longer effective.
      Participants were allocated to receive brentuximab vedotin at 1.4 mg/kg (phase 1)
      or 1.8 mg/kg (phases 1 and 2) via intravenous infusion once every 3 weeks for up
      to 16 cycles. Dose escalation was done via a 3+3 design. Key exclusion criteria
      were stem-cell transplantation less than 3 months before administration of the
      first dose of study drug, presence of cytomegalovirus infection after allogeneic
      stem-cell transplantation, previous treatment with an anti-CD30 antibody, and
      concurrent immunosuppressive or systemic therapy for chronic graft-versus-host
      disease. Primary outcomes were safety profile in the safety-evaluable population
      and maximum tolerated dose, recommended phase 2 dose, pharmacokinetics (phase 1),
      and proportion of patients who achieved best overall response (phase 2; evaluated
      by an independent review facility) in the response-evaluable population. This
      trial is registered with ClinicalTrials.gov, number NCT01492088. FINDINGS:
      Between April 16, 2012, and April 4, 2016, we screened 41 paediatric patients and
      enrolled 36 (aged 7-18 years), of whom 19 had relapsed or refractory classical
      Hodgkin's lymphoma and 17 had relapsed or refractory systemic anaplastic large
      cell lymphoma. At the data cutoff (Oct 12, 2016), all 36 patients had
      discontinued study drug treatment; the most common reason was progressive disease
      (15 patients). The maximum tolerated dose was not reached. The recommended phase
      2 dose was 1.8 mg/kg. The proportion of patients who achieved overall response
      was 47% (95% CI 21-73) for classical Hodgkin's lymphoma and 53% (28-77) for
      systemic anaplastic large-cell lymphoma. All 36 patients had a treatment-emergent
      adverse event and 16 patients (44%) had at least one grade 3 or worse treatment
      emergent adverse event. The most common treatment-emergent adverse events were
      pyrexia (16 [44%] of 36) and nausea (13 [36%]). The most common grade 3 or worse
      treatment-emergent adverse events were neutropenia (four [11%]), increased gamma
      glutamyl transpeptidase (two [6%]), and pyrexia (two [6%]). 12 (33%) patients had
      transient, limited-severity peripheral neuropathy. Eight patients (22%) had a
      serious adverse event; three (8%) had a drug-related serious adverse event. One
      patient died of cardiac arrest (disease progression of a large huge mediastinal
      mass, unrelated to the study drug). Paediatric pharmacokinetic profiles were
      consistent with those from studies of adult patients. INTERPRETATION: Brentuximab
      vedotin has manageable toxicity and is associated with clinically meaningful
      responses in paediatric patients with relapsed or refractory Hodgkin's lymphoma
      or systemic anaplastic large-cell lymphoma, and could allow subsequent stem-cell
      transplantation in some patients who were initially ineligible for stem-cell
      transplantation. FUNDING: Millennium Pharmaceuticals Inc.

PMID- 30290903
TI  - Intensive treatment strategies in advanced-stage Hodgkin's lymphoma (HD9 and
      HD12): analysis of long-term survival in two randomised trials.
AB  - BACKGROUND: Although intensified chemotherapy regimens have improved tumour
      control and survival in advanced-stage Hodgkin's lymphoma, data on the long-term
      sequelae are scarce. We did preplanned follow-up analyses of the German Hodgkin
      Study Group (GHSG) trials HD9 and HD12 to assess whether the primary results of
      these trials-which had shown that intensive initial therapy in advanced-stage
      Hodgkin's lymphoma has a beneficial effect on treatment outcomes-would continue
      with longer follow-up. METHODS: In HD9 (Feb 1, 1993, to March 10, 1998), 1282
      patients with newly diagnosed, histology-proven, advanced-stage Hodgkin's
      lymphoma received eight alternating cycles of COPP and ABVD (COPP/ABVD), eight
      cycles of bBEACOPP, or eight cycles of eBEACOPP. In HD12 (Jan 4, 1999, to Jan 13,
      2003; registered with ClinicalTrials.gov [NCT00265031]), 1670 patients with newly
      diagnosed, histology-proven, advanced-stage Hodgkin's lymphoma received eight
      cycles of eBEACOPP or four cycles of eBEACOPP plus four cycles of bBEACOPP (4 +
      4), plus consolidation radiotherapy to initial bulk and residual disease or no
      radiotherapy, to analyse two non-inferiority objectives. In both trials,
      randomisation was done centrally in the GHSG trial coordination centre using the
      minimisation method including a random component, stratified according to centre,
      age, stage, international prognostic score, the presence or absence of a large
      mediastinal mass, and bulky disease. Patients and investigators were not masked
      to treatment allocation. All analyses were done on the intention-to-treat
      principle. The primary endpoint of this follow-up analysis was progression-free
      survival (time from first diagnosis to progressive disease, relapse, or death
      from any cause or censoring at the date of last information on disease status).
      To assess whether long-term outcome might be impaired by long-term sequelae, we
      analysed overall survival and second primary malignant neoplasm incidence as key
      secondary endpoints. FINDINGS: Median observation time was 141 months (IQR 101
      204) in HD9 and 97 months (69-143) in HD12. For HD9 trial patients, 15-year
      progression-free survival was 57.0% (95% CI 50.0-64.0) for COPP/ABVD, 66.8% (61.9
      71.8) for bBEACOPP, and 74.0% (69.0-79.0) for eBEACOPP, 15-year overall survival
      was 72.3% (95% CI 66.5-78.1), 74.5% (70.1-78.9), and 80.9% (76.7-85.0),
      respectively. Progression-free survival and overall survival in the eBEACOPP
      group remained significantly better than in the COPP/ABVD group (hazard ratio
      [HR] 0.53, 95% CI 0.41-0.69, p<0.0001, and 0.68, 0.50-0.93, p=0.015,
      respectively). The 15-year cumulative incidence of second primary malignant
      neoplasms was 7.2% (95% CI 3.7-10.7) after COPP/ABVD, 13.0% (9.1-16.9) after
      bBEACOPP, and 11.4% (7.6-15.1) after eBEACOPP. For HD12 trial patients, non
      inferiority of 4 + 4 was shown, with 10-year progression-free survival of 82.6%
      (95% CI 79.6-85.6) for eBEACOPP and 80.6% (77.4-83.7) for 4 + 4 (HR 1.13 [0.89
      1.43], within non-inferiority margin of 1.50), and 10-year overall survival of
      87.3% (95% CI 84.7-89.9) and 86.8% (84.2-89.4), respectively (HR 1.02 [95% CI
      0.77-1.36]). Among 555 (37%) patients with residual disease after chemotherapy,
      omission of radiotherapy was associated with significantly worse 10-year
      progression-free survival (89.7% [95% CI 85.8-93.6] radiotherapy vs 83.4% [78.2
      88.5] for no radiotherapy; p=0.027) and 10-year overall survival (94.4% [91.4
      97.3] vs 88.4% [83.8-93.0]; p=0.025). 10-year cumulative second primary malignant
      neoplasms incidence was 6.4% (95% CI 3.3-9.5) for 4 + 4 and 8.8% (5.2-12.4) for
      eBEACOPP. INTERPRETATION: Long-term follow-up of HD9 and HD12 shows an ongoing
      benefit of intensive first-line treatment and consolidation radiotherapy to
      residual disease in terms of progression-free survival and overall survival. Our
      results support the use of eBEACOPP in advanced-stage Hodgkin's lymphoma.
      However, because late toxicities such as second primary malignant neoplasms
      contribute to mortality, less toxic but equally effective treatments need to be
      developed to further improve overall survival. FUNDING: Deutsche Krebshilfe e.V.

PMID- 30290904
TI  - Passive transfer of anti-HBc after intravenous immunoglobulin administration in
      patients with cancer: a retrospective chart review.
AB  - BACKGROUND: Patients previously infected with hepatitis B virus (HBV; indicated
      by positivity for anti-HBc) can experience HBV reactivation during cancer
      chemotherapy. Intravenous immunoglobulin infusion, which is frequently used in
      supportive care, might facilitate passive transfer of anti-HBc. We aimed to
      estimate the probability of passive transfer of anti-HBc after intravenous
      immunoglobulin infusion in patients with cancer. METHODS: We reviewed
      institutional databases to identify adult patients who received outpatient
      chemotherapy between Jan 1, 2004, and Dec 31, 2011, at the University of Texas MD
      Anderson Cancer Center, Houston, TX, USA. Eligible patients had received
      intravenous immunoglobulin therapy, had tested negative for both anti-HBc and
      HBsAg before infusion, and had been tested for anti-HBc after infusion. The
      primary endpoint was the proportion of patients who became positive for anti-HBc
      after intravenous immunoglobulin infusion. FINDINGS: 950 of 18 874 patients who
      underwent chemotherapy within the study time frame received intravenous
      immunoglobulin, of whom 870 had been tested for anti-HBc before infusion. 199
      patients who were negative for anti-HBc before receiving intravenous
      immunoglobulin were retested after infusion, of whom 29 (15% [95% CI 10-20])
      became positive for anti-HBc. The probability of anti-HBc conversion at 1 week
      after intravenous immunoglobulin infusion was 34% (95% CI 22-48) and at 12 weeks
      was 4% (2-7). INTERPRETATION: Conversion of patients from anti-HBc negativity to
      anti-HBc positivity was common after intravenous immunoglobulin administration.
      However, the probability of a positive test decreased with time since infusion.
      Positive anti-HBc tests done shortly after intravenous immunoglobulin infusion
      should be interpreted with caution because they might indicate passive transfer
      instead of true infection. FUNDING: None.

PMID- 30290905
TI  - Thalidomide before and after autologous stem cell transplantation in recently
      diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3,
      randomised controlled trial.
AB  - BACKGROUND: In patients with recently diagnosed multiple myeloma, the HOVON-50
      phase 3 trial showed improved event-free survival for thalidomide-containing
      induction and maintenance regimens (in conjunction with high-dose melphalan and
      autologous stem cell transplantation [auto-SCT]) after a median of 52 months of
      follow-up, by comparison with regimens containing classical cytotoxic drugs. In
      this follow-up analysis, we aimed to determine the long-term effects of
      thalidomide in induction and maintenance therapy in multiple myeloma. METHODS: In
      this open-label, phase 3 randomised controlled trial, patients with recently
      diagnosed multiple myeloma were recruited from 44 Dutch and Belgian hospitals.
      Participants had been diagnosed with multiple myeloma of Durie-Salmon stage II or
      III and were aged 18-65 years. Patients were randomly assigned (1:1) either to
      receive three 28-day cycles of vincristine (0.4 mg, intravenous rapid infusion on
      days 1-4), doxorubicin (9 mg/m2, intravenous rapid infusion on days 1-4) and
      dexamethasone (40 mg, orally on days 1-4, 9-12, and 17-20; control group); or to
      receive the same regimen, but with thalidomide (200-400 mg, orally on days 1-28)
      instead of vincristine (thalidomide group). No masking after assignment to
      intervention was used. Patients were randomly assigned to groups, stratified by
      centre and treatment policy (one vs two courses of high-dose melphalan and auto
      SCT). After stem cell harvest, patients received one or two courses of 200 mg/m2
      melphalan intravenously with auto-SCT. Patients with at least a partial response
      to high-dose melphalan and auto-SCT were eligible for maintenance therapy,
      starting 2-3 months after high-dose melphalan. Patients in the control group
      received maintenance therapy with interferon alfa (3 *  106 international units,
      subcutaneously, three times weekly). Patients in the thalidomide group received
      thalidomide as maintenance therapy (50 mg, orally, daily). Maintenance therapy
      was given until relapse, progression, or the occurrence of adverse events. The
      primary endpoint of the study was event-free survival (EFSc; censored at
      allogeneic stem cell transplantation), analysed by intention to treat. The study
      is closed for enrolment and this Article represents the final analysis. This
      trial was registered with the Netherlands Trial Register, number NTR238.
      FINDINGS: Between Nov 27, 2001 and May 31, 2005, 556 patients were enrolled in
      the study, of whom 536 (96%) were eligible for evaluation and were randomly
      allocated (268 [50%] to the control group and 268 [50%] to the thalidomide
      group). These 536 patients were assessed for the primary endpoint of EFSc. At an
      extended median follow-up of 129 months (IQR 123-136), EFSc was significantly
      longer in the thalidomide group compared with the control group (multivariate
      analysis hazard ratio [HR] 0.62, 95% CI 0.50-0.77; p<0.0001). Thalidomide
      maintenance was stopped because of toxicity in 65 (42%) of 155 patients in the
      thalidomide group (neuropathy in 49 [75%] patients, skin reactions in four [6%]
      patients, fatigue in two [3%] patients, and as other symptoms [such as abdominal
      pain, pancreatitis, and dyspnoea] in ten [15%] patients). 24 (27%) of 90 patients
      in the control group discontinued protocol treatment during maintenance therapy
      with interferon alfa because of toxicity (five [21%] patients with psychiatric
      side-effects, five [21%] patients with flu-like symptoms, four [17%] patients
      with haematological toxicity [thrombocytopenia and leucocytopenia], three [13%]
      patients with skin reactions, and seven [29%] patients with other symptoms [such
      as infections, cardiomyopathy, and headache]). The frequency of second primary
      malignancies was similar in both groups. There were 23 second primary
      malignancies in 17 patients in the control group and 29 second primary
      malignancies in 24 patients in the thalidomide group. There were 19 treatment
      related deaths in the control group, and 16 treatment-related deaths in the
      thalidomide group. INTERPRETATION: Our data indicate that thalidomide-based
      treatment could be a treatment option for patients with multiple myeloma who are
      eligible for auto-SCT who live in countries without access to proteasome
      inhibitors or lenalidomide. However, careful follow-up and timely dose
      adjustments are important to prevent the development of thalidomide-induced
      neurotoxicity. FUNDING: The Dutch Cancer Foundation.

PMID- 30290906
TI  - [Screening for familial hypercholesterolemia from low-density lipoprotein
      cholesterol levels at admission in the coronary care unit].
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is a frequent genetic disorder
      that leads to premature atherosclerosis and coronary artery disease. However,
      knowledge of FH by cardiologists is weak, and FH remains underdiagnosed in
      France. FH should be suspected when low-density lipoprotein cholesterol (LDLc)
      levels exceed 1.9g/L (4.9mmol/L) without lipid lowering therapy. PURPOSE: This
      multicenter retro- and prospective observational study aimed at estimating the
      prevalence of high LDLc levels in patients admitted in coronary care units, and
      the impact for the personal and familial follow-up for lipid status. METHODS:
      Retrospective analysis of all plasma lipid measurements performed at admission in
      coronary care unit of 4 hospitals in 2017. Retrospective analyses of demographic,
      clinical, and coronary data of consecutive patients with LDLc levels>=1.9g/L.
      Prospective 1 year follow-up focused on lipid levels, treatments, and personal
      and familial screening for FH. RESULTS: Lipid measurement has been performed in
      2172 consecutive patients, and 108 (5%) had LDLc level>=1.9g/L (mean age 64+/-14
      years, men 51%). The primary cause of the hospitalisation was acute coronary
      syndrome (78%), and 22% of patients were free off coronary artery disease. Lipid
      lowering therapy was present in 9% of patients at admission, and 84% at
      discharge, with high statins regimen. At 1-year follow-up, control of LDLc level
      was not performed in 20% of patients, and statin dose was decreased (36%) or
      withdrawn (7%) in 43%. Lipid measurement has been performed in at least one first
      degree relative in 37% of patients, and genetic exploration has been done for 3
      patients. CONCLUSIONS: Screening of FH in CCU should be routinely performed using
      the Dutch Score when LDLc is above 1.9g/L. Individual and familial management of
      patients at high risk for FH screened in CCU should be optimized, both for
      diagnosis and therapeutic purposes.

PMID- 30290907
TI  - [Cardiovascular complications of doping products].
AB  - Doping is the use of a substance that artificially increases an individual's
      physical ability for competition purpose. Products and methods used in doping are
      not without risk, especially at cardiovascular level. Here we review the most
      common doping substances in sport and their cardiovascular consequences.

PMID- 30290908
TI  - [An unusual cause of hypertension].
AB  - Secondary hypertension is relatively rare. Its etiologies are essentially renal
      or endocrine. The adrenocortical carcinoma, a rare malignant tumor, is one of the
      most exceptional causes of hypertension. We report the case of a young woman
      presenting with hypertension and ascites of great abundance. She had hypokalemia,
      hepatic cytolysis and cholestasis. Thoracic, abdominal and pelvic CT scans showed
      adrenal mass, liver and lung nodules, osteolytic lesions of the sacrum. The
      biopsy of liver nodules confirmed the diagnosis of a metastatic malignant
      adrenocortical carcinoma. The hormonal investigations revealed cortisol and
      testosterone hypersecretion. The evolution was quickly fatal, the patient passed
      out a few days after her hospitalization.

PMID- 30290909
TI  - [Left ventricular non-compaction: What should be known!]
AB  - Isolated non-compaction of the left ventricle (NCVG) is a rare congenital
      cardiomyopathy resulting from the shutdown of normal embryogenesis of the
      myocardium. Its main feature is the existence of many deep heart-related
      ventricular trabeculations, generally located at the level of the apex of the
      left ventricle. Diagnosis is based on echocardiography and magnetic resonance
      imaging (MRI), and may be difficult in the atypical forms. The clinical
      presentation and the prognosis are very variable. Familial forms are not rare,
      ordering a family screening.

PMID- 30290910
TI  - Reduction of radiation exposure associated with renewal of the radiologic systems
      in coronary interventions.
AB  - PURPOSE: Interventional coronary procedures are an important source of radiation.
      This study sought to evaluate the effect of the renewal of the radiologic system
      on patient exposure during diagnostic coronary angiography (DCA) and percutaneous
      coronary interventions (PCIs). METHODS: DCA and PCIs were obtained from three
      centres, which renewed their radiologic systems during their participation in the
      multicentre prospective observational RAY'ACT-2 study. Data were analysed from
      the months before and after the radiologic system was changed. The primary
      outcomes were the dose reduction estimated by the kerma.area product (KAP in
      Gy.cm2) and the ratio of the KAP to fluoroscopy time (Gy.cm2.min-1). RESULTS: A
      total of 2148 patients underwent DCA (1575 before and 573 after the system
      change), and 1563 underwent PCI (1196 before and 367 after). A change in the
      radiologic system was associated with a KAP reduction of 43% for DCA (median
      [interquartile range]: 18.1Gy.cm2 [10.2-34.0] versus 31.5 [19.0-49.0], P<0.0001),
      and 38% for PCI (42.2Gy.cm2 [23.8-81.7] versus 70.1 [42.0-109.0], P<0.0001).
      Fluoroscopy time did not vary significantly, and the ratio KAP to fluoroscopy
      time significantly decreased by 54%. The dose reduction was homogeneous between
      the three centres and between different manufacturer's systems. CONCLUSIONS: In
      this multicentre study, the renewal of the radiologic system was associated with
      a highly significant 40%-50% reduction in radiation dose, irrespective of the
      manufacturer. A close interaction between manufacturers and operators is needed
      to optimise the use of new equipment and the effectiveness of radiation reduction
      tools and techniques.

PMID- 30290911
TI  - [A (too) successful renal denervation].
AB  - We report the case of a type-2 myocardial infarction immediately after renal
      denervation. The patient was followed for coronary artery disease. Low blood
      pressures were responsible for inferior acute myocardial infarction that revealed
      a sub occlusive stenosis of the right coronary artery.

PMID- 30290913
TI  - Speckle tracking echocardiography in systemic sclerosis: A useful method for
      detection of myocardial involvement.
AB  - BACKGROUND: Systemic sclerosis is a multisystem disorder characterized by tissue
      fibrosis and organ damage. Heart involvement is one of the main factors
      shortening survival, which may be underestimated by conventional echocardiography
      measurements. Two-dimensional speckle-tracking echocardiography is a powerful
      novel modality to assess subclinical myocardial dysfunction. AIM: The aim of this
      study is to investigate heart involvement in systemic sclerosis patients, and to
      determine the usefulness of ventricular longitudinal deformation using the Two
      dimensional speckle tracking technology for an early detection of ventricular
      dysfunction. PATIENTS AND METHODS: Between May 2016 and September 2016, 25
      patients with systemic sclerosis and 25 healthy subjects underwent
      echocardiography to assess heart abnormalities and the strain of the two
      ventricles using two dimensions' speckle tracking echography. RESULTS: The two
      groups were comparable in age and gender. Despite comparable left ventricle
      systolic function (left ventricular ejection fraction patients 64.58+/-8.87 vs.
      in healthy 68.2+/-7.41, P=0.19), patients presented altered longitudinal peak
      systolic strain values (global longitudinal strain: patients -17.42+/-1.62 vs.
      healthy -19.24+/-8.85, P<0.0001). Despite comparable pulmonary artery systolic
      pressure, there was a significant alteration in right ventricular systolic and
      diastolic function assessed by standard measurement. Longitudinal peak systolic
      strain of the right ventricle was significantly lower in patients compared with
      controls (P<0.01). CONCLUSION: Ventricular deformation analysis by two
      dimensions' speckle tracking echocardiography appears to be a sensitive method to
      detect early ventricular impairment in patients with systemic sclerosis.

PMID- 30290912
TI  - [Echocardiographic profile of Congolese hypertensive patients].
AB  - OBJECTIVES: To assess echocardiographic aspect of Congolese hypertensive
      patients, and to identify predictive factors of left ventricular hypertrophy
      (LVH). PATIENTS AND METHODS: A transversal study was lead in Brazzaville from
      January 2011 to December 2013 (36 months). In total, 1125 hypertensive patients
      under treatment underwent transthoracic echocardiography. The test was carried
      out either as part of an initial assessment of the hypertension disease or during
      the development of evocative symptom or complication. Patients' sociodemographic
      data and echocardiographic parameters were collected and analyzed. RESULTS: There
      were 621 males (55.2%) and 504 females (44.8%), mean age 54.7+/-12 years. The
      main indication of the test were the hypertension initial evaluation in 792 cases
      (70.4%), dyspnea in 122 cases (10.8%), investigation of ischemic stroke in 101
      cases (9%), cardiac failure and chest pain in respectively 58 and 52 cases. 5.3+/
      4.7 years known duration of hypertension status was associated with
      overweight/obesity in 829 cases (73.7%), physical inactivity in 669 cases
      (59.5%), hypertension family history in 540 cases (48%), diabetes mellitus in 122
      cases (10.8%), dyslipidemia in 82 cases (7.3%), smoking in 29 cases (2.6%).
      Echocardiographic test was abnormal in 590 cases (52.4%) and showed hypertrophic
      cardiomyopathy in 510 cases (45.2%), dilated and hypertrophic cardiomyopathy in
      46 cases (4.1%), dilated cardiomyopathy with systolic dysfunction in 31 cases
      (2.8%), coronary artery disease in 4 cases (0.4%). LVH was concentric in 470
      cases (84.6%), eccentric in 70 cases (12.6%), and in 16 cases (3%), it was a
      concentric left ventricular remodeling. The left ventricular's systolic ejection
      fraction average was 70.5+/-9.3%, relaxation disorders in 480 cases (42.6%). Age,
      male gender, income, known duration of hypertension and treatment were predictive
      factors of LVH. CONCLUSIONS: Echocardiographic profile of the Congolese
      hypertensive is quite various, left ventricular hypertrophy is the most
      predominant abnormality. Efficient management on the hypertension will lead to
      reduce its morbidity and mortality.

PMID- 30290914
TI  - [Thrombolysis in pulmonary embolism with high mortality risk: Experience of a
      cardiology department in sub-Saharan Africa].
AB  - INTRODUCTION: High-risk pulmonary embolism (PE) accounts for 5% of total acute PE
      and is a life-threatening emergency requiring immediate therapeutic management by
      fibrinolysis. The objective of this work is to describe the experience of
      thrombolysis in high-risk PE in a cardiology department in Togo. PATIENTS AND
      METHODS: This is an analytical and descriptive study carried out in the
      cardiology department of the Campus teaching hospital of Lome over a period of 5
      years (August 2012 to July 2017) concerning patients hospitalized for high-risk
      mortality PE and having undergone streptokinase thrombolysis. RESULTS: Twenty
      eight of the 102 PE were at high risk of mortality (27.5%). They were 9 men and
      19 women with an average age of 61.9+/-14.1 years. The mean systolic blood
      pressure was 65mmHg and 50% of the patients were placed on dobutamine.
      Thrombolysis was performed in 22 of the 28 patients (78.6%). Eighteen patients
      had a short protocol and 4 a long protocol. The mortality rate was 32.1% or 13.6%
      in the thrombolysis PE versus 100% in the non-thrombolysis PE (P=0.01). Causes of
      death in thrombolysis were persistent shock (2 cases) at the end of thrombolysis
      and sudden death occurred 1 month after hospitalization. The average hospital
      stay was 18.8 days. CONCLUSION: The high-risk PE remains today a pathology
      burdened with heavy mortality. Thrombolysis remains the first treatment to reduce
      this mortality.

PMID- 30290915
TI  - [Obesity, high blood pressure and physical activity levels in a black African
      population].
AB  - PURPOSE OF THE STUDY: To determine the prevalence of general and abdominal
      obesity and to describe their association with high blood pressure and physical
      activity levels in a peri-urban population in West Africa. METHODS: A cross
      sectional study was conducted in Abidjan (Cote d'Ivoire) in the Anonkoi 3
      district, from 24 April to 23 May 2014. Obesity, abdominal obesity and physical
      activity levels were assessed. Blood pressure was measured. The data were entered
      on the Epi data software (version 3.1) and analyzed with the R studio software
      version 1.1.447. The existence of associations was demonstrated by the Pearson
      Khi2 test at the 0.05 significance level. A multivariate analysis was performed.
      RESULTS: We recruited 486 adults 18 years of age and older, including 327 women
      and 159 men. The average age was 36.1 years with a standard deviation of 12.83
      years. The prevalence of obesity was 14.8 %, that of abdominal obesity 50.8 % or
      more than half of the population. Females (P=0.000), ages 30 years and older
      (P=0.003), high blood pressure (P=0.000) and low activity (P=0.033) were
      significantly associated with obesity and abdominal obesity. Multivariate
      analysis showed that the relationship between female gender and abdominal obesity
      was very significant (OR=48.52; 95 % CI). CONCLUSION: This village located in a
      municipality of Abidjan has a heterogeneous population. This one adopts the
      sedentary habits of the city.

PMID- 30290916
TI  - [Analysis of cardiovascular complications occurring during inter-hospital
      transfers of patients with non-ST elevation myocardial infarction].
AB  - AIM OF THE STUDY: Patients with non ST-segment elevated acute coronary syndrome
      justify specific management in a hospital with an Intensive Cardiac Care Unit. In
      our area, these transfers are often provided by the Emergency Medical Service.
      Nevertheless we wonder whether a quasi-systematic medicalization of these
      patients is rational. PATIENTS AND METHOD: We tried to authenticate the need for
      medicalization of these patients through a prospective study including any
      patient with acute non-ST elevation Coronary Syndrome managed in one of the
      peripheral hospitals of the area and transferred to the major hospital center in
      La Roche-sur-Yon. We noted all the complications that occurred during the
      transfer and, if need be, when these complications required medical intervention.
      RESULTS: Out of 226 patients included, 19 had a complicated form of acute non-ST
      elevation Coronary Syndrome. Out of the remaining 207 patients, 16 (7.7 %) showed
      a complication during their transfer, 5 of which underwent a medical
      intervention, none of which was immediately vital. Nevertheless, the statistical
      analysis did not highlight any significant worsening factors. CONCLUSION: The low
      rate of complications occurring during the transfer of initially stable patients
      encourages us to limit our indications of medicalization in favour of only the
      unstable patients or having a complication of their non-ST elevation acute
      coronary syndrome.

PMID- 30290917
TI  - [Prevalence and determinants of the increased carotid intima-media thickness in a
      population of 1203 black African hypertensive].
AB  - OBJECTIVES: To evaluate the prevalence and determinants of increased carotid
      intima-media thickness (IMT) in a population of black hypertensive patients and
      it influence of on the assessment of their overall cardiovascular risk. PATIENTS
      AND METHODS: This was a 16-month, cross-sectional study conducted in the
      outpatient unit of the cardiology department of the Campus teaching hospital of
      Lome, and included 1203 hypertensive patients, both sexes, aged 35 years and
      more. Each patient benefited from a carotid IMT measure. Carotid IMT was
      increased if it was>0.9mm and the plaque was defined as a carotid IMT>1.2mm.
      RESULTS: The mean age of our patients was 53.3+/-10.4 years with a sex ratio of
      1.6 in favor of women. The duration of hypertension was less than 5 years in
      56.7% and hypertension was grade 1 in 47.7% of cases. The mean carotid IMT was
      0.89mm+/-0.20. The prevalence of the increased carotid IMT was 45.8% and that of
      an atheroma plaque was 15.8%. Carotid IMT was correlated with age (P?0.0001),
      duration of arterial hypertension (P=0.01), history of stroke (P?0.0001), and
      presence of left ventricular hypertrophy to cardiac ultrasound (P=0.01). The
      overall cardiovascular risk was modified after taking into account the carotid
      IMT. An increase in cardiovascular risk was observed in 30.5% of hypertensive
      patients. CONCLUSION: Increased carotid intima-media thickness is frequent in
      Togolese hypertension. The determining factors are age, duration of arterial
      hypertension, left ventricular hypertrophy and stroke. The systematic measurement
      of the carotid intima-media thickness would better evaluate the overall
      cardiovascular risk for our patients.

PMID- 30290918
TI  - [Effect of frontal electrodes location on the electrocardiogram quality of obese
      subjects: Roots versus limb of extremities].
AB  - INTRODUCTION: In obese patients, standard recording of electrocardiogram seems to
      have specific electrical modifications related to obesity. These modifications
      could be minimized by the use of alternative recording techniques. The aim of
      this study is to evaluate the effect of the recording technique (standard versus
      Lund) on the electrocardiogram quality in healthy obese patients. METHOD: This is
      an observational and descriptive study carried out in emergency medical services
      during a two years period. Healthy subjects with an age over 18 years and a body
      mass index (BMI)>=30kg/m2 were included. Each participant had an
      electrocardiogram according to Lund's technique immediately followed by a
      standard recording. Deflections amplitude and their respective axes were compared
      between the two techniques. The primary endpoint was the frequency of
      microvoltage. The secondary endpoints were the flat T wave at the inferior and
      the left axial deviations. RESULTS: Fifty obese patients were included. The
      average BMI was 36.8+/-6.6kg/m2. The average age was 45+/-13 years with a sex
      ratio of 0.52. The standard technique was associated with a higher incidence of
      microvoltage (40% versus 20%, P=0.029) and flattening of the T wave (40% versus
      18%, P=0.015). Analysis of the variance of the P, QRS and T wave axes did not
      find any difference between the two techniques. CONCLUSION: The Lund technique
      reduces the incidence of electrical abnormalities in the electrocardiogram of
      healthy obese patients.

PMID- 30290920
TI  - New biomedical polymer targeting E-selectin to reduce atherosclerosis.

PMID- 30290919
TI  - [Left atrial intimal sarcoma: A rare cause of acute heart failure].
AB  - Primitive intimal sarcoma is a rare malignant cardiac tumor. Through the
      observation of a 41-year-old man who presented with an acute heart failure
      revealing a left atrial intimal sarcoma, we discuss different diagnostic and
      therapeutic modalities.

PMID- 30290922
TI  - Bronchiectasis and Chronic Airway Disease: It Is Not Just About Asthma and COPD.

PMID- 30290921
TI  - Increasing Suicide Rates Across Asia- A Public Health Crisis.

PMID- 30290923
TI  - Sleep, Circadian Disruption, and Microbial-Immune Interactions: A New Frontier.

PMID- 30290924
TI  - Pleural Biopsy to Capture Causative Microbe: A New Piece of the Pleural Infection
      Jigsaw.

PMID- 30290925
TI  - POINT: Should LAMA/LABA Combination Therapy Be Used as Initial Maintenance
      Treatment for COPD? Yes.

PMID- 30290926
TI  - COUNTERPOINT: Should LAMA/LABA Combination Therapy Be Used as Initial Maintenance
      Treatment for COPD? No.

PMID- 30290927
TI  - Rebuttal From Drs Cazzola and Matera.

PMID- 30290928
TI  - Rebuttal From Drs Barrecheguren and Miravitlles.

PMID- 30290929
TI  - Practical Tips for ICU Bedside Teaching.

PMID- 30290930
TI  - Focus on Idiopathic Pulmonary Fibrosis: Advancing Approaches to Diagnosis,
      Prognosis, and Treatment.
AB  - As seen in this CME online activity (available at
      http://courses.elseviercme.com/694), idiopathic pulmonary fibrosis (IPF) is a
      specific form of chronic, progressive, fibrotic lung disease of unknown cause
      that is associated with substantial health-care utilization and high rates of
      mortality. The clinical symptoms of IPF are nonspecific and overlap with many
      pulmonary and cardiac diseases making differential diagnosis challenging. The
      American Thoracic Society/European Respiratory Society/Japanese Respiratory
      Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) guidelines
      strongly recommend a multidisciplinary approach to the diagnosis of interstitial
      lung diseases; however, there are several limitations to the feasibility of this
      approach in clinical practice. Although early diagnosis is relevant to any
      chronic, progressive, and irreversible disorder, it is crucially important that
      effective treatments for IPF are prescribed without delay. A window of
      opportunity may exist during which time treatment can have optimal outcomes.
      Evidence on the clinical management of IPF is rapidly evolving, and key updates
      were made to the most recent ATS/ERS/JRS/ALAT guidelines. The widely used
      combination of prednisone, azathioprine, and N-acetylcysteine has now been
      associated with increased risk of hospitalization and death compared with placebo
      in patients with IPF. These treatments and others for IPF have been mostly
      supportive, but recently pirfenidone and nintedanib have demonstrated efficacy in
      reducing functional decline and disease progression in IPF. A pooled analysis of
      three phase 3 studies of pirfenidone found a significant 48% reduction in all
      cause mortality, and a pooled analysis of a phase 2 and two phase 3 studies of
      nintedanib found a significant 43% reduction in on-treatment mortality. As
      patient exposure to these two new drugs increases, data continue to emerge on how
      and when to use these medications and on how to manage their side effects.
      Finally, several medications targeting the fibrotic pathobiology of IPF are
      currently in development. Given the limited treatment options for IPF, enrollment
      in a clinical trial may be the best chance to delay or prevent progression of
      IPF. This CME-certified expert video roundtable from CHEST reviews the
      ATS/ERS/JRS/ALAT guidelines with a specific focus on accurate and timely
      diagnosis of IPF and the latest data on the treatment of IPF.

PMID- 30290931
TI  - Breathing Life Into COPD Management: Ongoing Monitoring, Pulmonary
      Rehabilitation, and Individualized Care.
AB  - As seen in this CME online activity (available at
      http://copdcme.elsevierresource.com/, COPD is characterized by pulmonary airflow
      obstruction that is not completely reversible. COPD presents clinically with
      diverse phenotypes ranging from relatively asymptomatic people to patients with
      severe chronic cough, abnormal sputum production, and dyspnea with exertion.
      Exacerbations accelerate the downward cycle of breathing difficulties, activity
      avoidance, and physical decline that characterizes progressive COPD.
      Consequently, patients with COPD should be repeatedly assessed for symptom
      severity and duration, previous exacerbations, the degree of airflow limitation,
      and confounding comorbidities. Spirometry should be used to clarify COPD
      prognoses and longitudinally classify the disease from mild to very severe.
      Conversely, spirometry does not always capture the wide-ranging effects of COPD
      on patient function and quality of life, and other clinical assessment tools and
      evaluation strategies should be used to longitudinally monitor patients. Although
      COPD cannot currently be cured, all disease stages can be treated to slow
      progression, minimize symptoms, prevent exacerbations, and maximize function and
      quality of life. Importantly, all patients should participate in comprehensive
      pulmonary rehabilitation regardless of disease stage. Patients and providers,
      however, can be unaware of potential benefits or reluctant to initiate this
      modality. In many practice settings, finding a pulmonary rehabilitation program
      to accept the patient can be difficult, highlighting the need for well-defined
      referral pathways. Almost all patients with COPD also require pharmacotherapy to
      control symptoms, reduce complications, and maximize lung function. Evidence
      based education that addresses individualized maintenance regimens are needed to
      improve long-term outcomes in COPD. Within this CME/CE Snapshot educational
      series, an expert pulmonologist and a primary care educator discuss how to best
      longitudinally evaluate patients with COPD and incorporate the principles of
      pulmonary rehabilitation to maximize patient function and quality of life. They
      explain therapeutic tailoring over the course of disease and describe the
      importance of engaging patients in shared decision-making to promote acceptance
      of the diagnosis, appropriate physical activity, and treatment adherence.

PMID- 30290932
TI  - Clinical Issues in Severe Asthma: Consensus and Controversies on the Road to
      Precision Medicine.
AB  - As seen in this CME online activity (available at
      http://courses.elseviercme.com/708e), the various forms of asthma affect > 300
      million people globally and > 25 million people in the United States. Asthma
      related symptoms and exacerbations result in nearly 2 million ED visits annually,
      and many of these visits lead to inpatient hospital stays. There is an urgent
      need to improve the care of the estimated 5% to 15% of patients who have severe
      asthma. Importantly, studies have shown that severe asthma accounts for an
      outsized proportion of the disease-related morbidity, mortality, and health-care
      costs. Examining cohorts from several large patient networks that were created to
      better understand clinical presentations, biopsychosocial consequences, and long
      term outcomes of severe asthma revealed substantial disease burden, significant
      gaps in longitudinal care, and a clear need for additional treatment options.
      This CME-accredited Clinical Issues program is intended for allergists/clinical
      immunologists, pulmonologists, and other health-care providers involved in the
      management of patients with severe asthma. During the activity, a panel of expert
      faculty will discuss and debate a series of topics related to the evaluation and
      long-term treatment of various severe asthma phenotypes. Activity topics include
      education regarding (1) The classification of severe asthma to differentially
      diagnose patients with disease that is uncontrolled despite relatively intensive
      therapy; (2) potential phenotypes and available biomarkers, including strengths,
      limitations, and how to translate results into the selection of therapies; and
      (3) the different mechanisms of action, efficacy, and safety of biologic
      therapies that target the pathophysiology of severe asthma. The goal is to
      provide clinician learners with the latest evidence and a fresh perspective on
      evolving management paradigms for severe asthma.

PMID- 30290933
TI  - Confronting the Challenge of COPD: What Is New in the Approaches to Diagnosis,
      Treatment, and Patient Outcomes.
AB  - As seen in this CME online activity (available at
      http://courses.elseviercme.com/730), COPD is the third leading cause of death in
      the United States among people 65 years of age and older and the fourth leading
      cause of death among people 45 to 65 years of age. A recent survey reported that
      about 12 to 15 million people in the United States have physician-diagnosed COPD.
      However, COPD is significantly underdiagnosed, and data suggest as many as 12
      million people in the United States have undiagnosed COPD. In addition to being
      underdiagnosed, COPD is significantly undertreated, with numerous literature
      sources indicating that patients with COPD are not receiving guideline concordant
      pharmacotherapy. Consistent with these sources, an analysis of claims data for >
      50,000 patients with COPD indicated a high degree of undertreatment in these
      patients. For patients using an inhaler, adherence to inhaler medications and
      correct inhaler device technique are crucial to successful COPD management.
      However, the literature indicates > 50% of patients with COPD demonstrate poor
      medication adherence and rates of incorrect inhalation technique range from 35%
      to 85%. Studies have shown that regular training by a physician improved inhaler
      techniques among patients with COPD. Further, studies have shown that repeated
      instruction on inhalation techniques improved both adherence and quality of life
      outcomes. This CME-certified webcast provides insights into new approaches to
      identifying patients with undiagnosed COPD, the importance of early initiation of
      pharmacologic treatment in a guideline-congruent manner, and the importance of
      repeated patient training in correct inhaler techniques to improve adherence and
      patient outcomes. Additionally, the online program is part of a larger learning
      platform (available at https://copd.elsevierresource.com/) that provides free
      access to the latest clinical information related to the diagnosis and management
      of COPD. The COPD Learning Center is a freely accessible platform that aims to
      increase clinical knowledge by providing CME activities, research articles, and
      resources for health-care providers who treat patients with COPD.

PMID- 30290934
TI  - Housecleaner.

PMID- 30290935
TI  - Valley Fever Pantoum.

PMID- 30290936
TI  - Leveraging ICU Telemedicine to Reduce Low-Value Interhospital Transfer.

PMID- 30290937
TI  - Response.

PMID- 30290938
TI  - Impact of Small Group Practice Using a Respiratory Patient Simulator on Long-Term
      Knowledge Acquisition Among Internal Medicine Residents.

PMID- 30290939
TI  - Response.

PMID- 30290940
TI  - Management of Dyspnea in the Noncommunicative Patients: Consider Hetero
      evaluation Scales.

PMID- 30290942
TI  - Response.

PMID- 30290941
TI  - Response.

PMID- 30290943
TI  - Single-Arm Trials Can Be Used for Meta-analysis to Compare PD-1 Inhibitor With PD
      L1 Inhibitors on the Incidence of Pneumonitis?

PMID- 30290944
TI  - Pigtail Catheter Drainage Can Be Considered as the Initial Treatment Option for
      Patients With Pneumothorax: Not Yet Determined.

PMID- 30290945
TI  - Response.

PMID- 30290946
TI  - Consideration of Occupational and Environmental Lung Carcinogen Exposures for
      Lung Cancer Screening Using Low-Dose Chest CT.

PMID- 30290947
TI  - Response.

PMID- 30290948
TI  - Outcome Switching in Triple Therapy in Influenza A(H3N2) Infection: An Open-label
      Randomized, Controlled, Phase IIb/III Trial.

PMID- 30290949
TI  - Response.

PMID- 30290950
TI  - A 38-Year-Old Man With a 2-Month History of Fever, Cough, Palpitations, and
      Weight Loss.
AB  - CASE PRESENTATION: A 38-year-old man of Indian origin, who migrated to Greece 13
      years prior to presentation, was admitted to our hospital with a 2-month history
      of nonprogressive, intermittent (mostly evening), low-grade (up to 38.5 degrees
      C) fever, accompanied by night sweats, dry cough, mild dyspnea on exertion
      (modified Medical Research Council Dyspnea Scale grade 1), anorexia, fatigue, and
      weight loss of 10 kg. He also experienced continuous palpitations, which were
      regular, not associated with chest pain or dizziness, and aggravated on exertion.
      He had not taken any medication for his condition, except for antipyretic agents,
      nor had he sought medical advice. He was a nonsmoker, had a history of past
      alcohol dependence, and had been hospitalized twice for acute pancreatitis due to
      hypertriglyceridemia. He had also been diagnosed with diabetes mellitus,
      presumably poorly controlled because he mentioned not taking any medication or
      having regular follow-up.

PMID- 30290951
TI  - A 62-Year-Old Woman With Acute Respiratory Failure and a Painful Right Lower
      Limb.
AB  - CASE PRESENTATION: A 62-year-old woman with no medical history was admitted to
      the ED for fever, acute respiratory failure, and pain in the right lower limb.
      Three months prior to presentation, she had spent 45 days travelling through
      India and Thailand. She presented with no signs of traveler's disease such as
      fever or diarrhea during that trip. Two weeks following her return to France, the
      patient presented with an episode of bronchitis and received 5 days of treatment
      with cefixime (a third-generation cephalosporin). Despite this antibiotic
      treatment, her symptoms worsened and she developed, over the following 3 weeks,
      general weakness and arthralgia/myalgia. Due to the severity of hypoxemia, the
      patient was immediately transferred to the ICU.

PMID- 30290952
TI  - A 26-Year-Old Man With a Pleural Effusion and Headache.
AB  - CASE PRESENTATION: A 26-year-old man presented to the ED with dizziness and gait
      imbalance. He noted dizziness for 3 months, but symptoms progressed more rapidly
      over the last 3 weeks when he began experiencing nausea, vomiting, and "wobbly
      legs." These symptoms would worsen with physical exertion, especially when
      lifting heavy objects. On review of systems, he also reported subjective fevers
      and chills. He had no appreciable dyspnea, cough, chest pain, or increased sputum
      production. The patient recalled a history of "brain surgery" approximately 4
      years prior to his presentation, but no further details could be provided at the
      time.

PMID- 30290953
TI  - Pirfenidone-Induced Sarcoid-Like Reaction: A Novel Complication.
AB  - Idiopathic pulmonary fibrosis is the most common idiopathic interstitial
      pneumonia. Prognosis is poor with a median survival <3 years. Pirfenidone is one
      of two US Food and Drug Administration-approved medications that slow disease
      progression. We describe the development of lymphadenopathy or a sarcoid-like
      reaction following initiation of pirfenidone, a complication not previously
      reported.

PMID- 30290954
TI  - A 59-Year-Old Man in Refractory Shock.

PMID- 30290955
TI  - A 67-Year-Old Man With Palpitations During Sleep.
AB  - CASE PRESENTATION: A 67-year-old man with a history of atrial fibrillation (AF)
      presented to his physician with symptoms of episodic, nighttime palpitations and
      excessive daytime sleepiness. Four years prior he underwent radiofrequency
      ablation after a confirmed diagnosis of AF with subsequent resolution of his
      palpitations. His palpitations returned approximately 1 year following the
      ablation. These events would occur only at night and awake him from sleep. Holter
      monitoring showed baseline sinus rhythm with multiple episodes of AF with rates
      of 75 to 169 beats/min. These events were all nocturnal and correlated with the
      symptom diary; episodes ranged from 45 min to 2 h. An echocardiogram showed
      normal left ventricular size and ejection fraction with a mildly enlarged right
      atrium (4.38 cm) and no evidence of pulmonary hypertension.

PMID- 30290956
TI  - Genomic Differences Between "Primary" and "Secondary" Muscle-invasive Bladder
      Cancer as a Basis for Disparate Outcomes to Cisplatin-based Neoadjuvant
      Chemotherapy.
AB  - BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical
      cystectomy (RC) is the standard of care for patients with muscle-invasive bladder
      cancer (MIBC). It is unknown whether this treatment strategy is appropriate for
      patients who progress to MIBC after treatment for prior noninvasive disease
      (secondary MIBC). OBJECTIVE: To determine whether clinical and genomic
      differences exist between primary and secondary MIBC treated with NAC and RC.
      DESIGN, SETTING, AND PARTICIPANTS: Clinicopathologic outcomes were compared
      between 245 patients with clinical T2-4aN0M0-stage primary MIBC and 43 with
      secondary MIBC treated with NAC and RC at Memorial Sloan Kettering Cancer Center
      (MSKCC) from 2001 to 2015. Genomic differences were assessed in a retrospective
      cohort of 385 prechemotherapy specimens sequenced by whole-exome or targeted exon
      capture by the Cancer Genome Atlas or at MSKCC. Findings were confirmed in an
      independent validation cohort of 94 MIBC patients undergoing prospective targeted
      exon sequencing at MSKCC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Pathologic response rates, recurrence-free survival (RFS), bladder cancer
      specific survival (CSS), and overall survival (OS) were measured. Differences in
      somatic genomic alteration rates were compared using Fisher's exact test and the
      Benjamini-Hochberg false discovery rate method. RESULTS AND LIMITATIONS: Patients
      with secondary MIBC had lower pathologic response rates following NAC than those
      with primary MIBC (univariable: 26% vs 45%, multivariable: odds ratio=0.4 [95%
      confidence interval=0.18-0.84] p=0.02) and significantly worse RFS, CSS, and OS.
      Patients with secondary MIBC treated with NAC had worse CSS compared with
      cystectomy alone (p=0.002). In a separate genomic analysis, we detected
      significantly more likely deleterious somatic ERCC2 missense mutations in primary
      MIBC tumors in both the discovery (10.9% [36/330] vs 1.8% [1/55], p=0.04) and the
      validation (15.7% [12/70] vs 0% [0/24], p=0.03) cohort. CONCLUSIONS: Patients
      with secondary MIBC treated with NAC had worse clinical outcomes than similarly
      treated patients with primary MIBC. ERCC2 mutations predicted to result in
      increased cisplatin sensitivity were enriched in primary versus secondary MIBC.
      Prospective validation is still needed, but given the lack of clinical benefit
      with cisplatin-based NAC in patients with secondary MIBC, upfront RC or
      enrollment in clinical trials should be considered. PATIENT SUMMARY: A
      retrospective cohort study of patients with "primary" and "secondary" muscle
      invasive bladder cancer (MIBC) treated with chemotherapy before surgical removal
      of the bladder identified lower response rates and shorter survival in patients
      with secondary MIBC. Tumor genetic sequencing of separate discovery and
      validation cohorts revealed that chemotherapy-sensitizing DNA damage repair gene
      mutations occur predominantly in primary MIBC tumors and may underlie the greater
      sensitivity of primary MIBC to chemotherapy. Prospective validation is still
      needed, but patients with secondary MIBC may derive greater benefit from upfront
      surgery or enrollment in clinical trials rather than from standard chemotherapy.

PMID- 30290957
TI  - Keys to Amyloid City: Computation and NMR Reveal Potential TDP-43 ALS
      Intermediates.

PMID- 30290958
TI  - Evaluation of the thermal aging of aeronautical composite materials using Lamb
      waves.
AB  - This work aims to demonstrate the ability to evaluate bulk thermal aging of
      aeronautical composite materials using Lamb waves. These composite materials are
      bi-dimensional woven composite structures with polymers matrix. More than 20
      different thermal aging profiles are obtained by modulating the temperature and
      curing duration. The impact on material properties is evaluated using normalized
      destructive characterization and x-ray computed tomography. Lamb waves are
      generated and detected using a single 3 MHz phased array transducer in contact
      with the composite structure. In that way, a spatio-temporal image of elastic
      wave propagation in the composite material is obtained. The dispersion curves are
      calculated by using a bi-dimensional discrete Fourier transform or singular value
      decomposition to project the experimental data into the wavenumber-frequency
      domain. Both methods allow for accurate estimation of the Lamb wave dispersion
      curves. Thermal aging is then evaluated by comparing experimental data with a set
      of dispersion curves that correspond to different controlled thermal aging
      profiles. Our promising results open the door toward quantitative evaluation of
      composite material thermal aging on the runway.

PMID- 30290959
TI  - Will the new molecules be effective in renal and cardiovascular protection in
      diabetes mellitus and diabetic kidney disease?

PMID- 30290960
TI  - Fetal environment and fetal intestine are sterile during the third trimester of
      pregnancy.
AB  - Recent next generation sequencing studies on host-associated microbiomes
      generated debatable conclusions regarding the central dogma of fetal gut
      sterility. These observations challenge the concepts that microbial colonization
      of the gut begins during and after birth as well as the concept of antigen
      independent prenatal maturation of mucosal-associated lymphoid tissue in
      ruminants and humans. The placental barrier varies markedly among mammalian
      species with mice and humans having haemochorial placentas (fetal tissue in
      direct contact with maternal blood) versus epitheliochorial placentation
      (maternal and fetal blood separated by six tissue layers) in ruminants.
      Therefore, this study re-examined the question of fetal gut sterility using the
      fetal lamb as a model ruminant species with the most complete placental barrier.
      Use of PCR and quantitative real-time PCR with three different pairs of universal
      bacterial primers (27 F and 1492R, HDA1 and HDA2, U2F and U2R) to amplify 16S
      rRNA gene did not generate detectable PCR products from samples collected from
      the fetal environment (placenta, amniotic fluid) and fetal intestine during the
      third trimester of pregnancy. Procedures to further enrich microbial DNA from
      total extracted DNA also resulted in no detectable genomic DNA. Moreover, use of
      16S amplicon sequencing confirmed the absence of bacteria in the fetal
      environment during the third trimester of pregnancy. A 'No Template' control
      containing only PCR reagents generated sequences that could be clustered into
      OTUs at 97% similarity and assigned to bacterial genera, including
      Staphylococcus, Lactobacillus and Escherichia-Shigella. Use of multiple molecular
      based approaches to profile fetal environment-associated microbiota supports the
      conclusion that the fetal environment and fetal intestine remain sterile during
      the third trimester of pregnancy. The use of appropriate controls, both positive
      and no template, revealed inherent contamination in reagents and that variations
      in the data analysis pipeline can produce artificial microbial profiles from host
      tissues containing low microbial biomass. Finally, these findings confirm that
      extensive development of gut-associated lymphoid tissue in the ruminant fetal
      intestine, characterized by active B cell proliferation and immunoglobulin V gene
      somatic mutation, is not associated with exposure to bacterial DNA and antigens.

PMID- 30290961
TI  - Anaphylactic shock versus Kounis syndrome in cardiac surgery: Differential
      diagnosis.
AB  - Although Kounis syndrome was described almost 3 decades ago, there has been a
      notable increase in the reports of cases of acute coronary syndromes developed in
      the context of allergic reactions, also known as Kounis syndrome. This article
      discusses the diagnostic possibility in the face of an acute biventricular
      failure in the course of an anaphylactic reaction during the intra-operative
      period of a cardiac valve surgery.

PMID- 30290962
TI  - Chronic kidney disease measures and the risk of abdominal aortic aneurysm.
AB  - BACKGROUND AND AIMS: Despite its strong link to cardiovascular outcomes, the
      association of chronic kidney disease (CKD) with abdominal aortic aneurysm (AAA)
      has not been explicitly and comprehensively investigated. METHODS: In 10,724
      participants in the Atherosclerosis Risk in Communities Study (aged 53-75 years
      during 1996-1998), we evaluated the associations of two key CKD measures -
      estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio
      (ACR) - with incident AAA (AAA diagnosis in outpatient, hospitalization
      discharge, or death records). Additionally, we performed a cross-sectional
      analysis for the CKD measures and ultrasound-based abdominal aortic diameter in
      4258 participants during 2011-2013. RESULTS: During a median follow-up of 13.9
      years, 347 participants developed AAA. The demographically-adjusted hazard ratio
      (HR) was 4.44 (95% CI 1.58-12.49) for eGFR <30, 3.29 (1.89-5.72) for 30-44, 2.03
      (1.29-3.19) for 45-59, and 1.62 (1.11-2.35) for 60-74 compared to eGFR >=90
      mL/min/1.73 m2 and was 2.49 (1.28-4.87) for ACR >=300, 1.99 (1.40-2.83) for 30
      299, and 1.46 (1.08-1.97) for 10-29 compared to ACR <10 mg/g. The associations
      were generally similar after accounting for additional confounders, such as
      smoking (although attenuated), or after stratifying by subgroups, including
      diabetes. The cross-sectional analysis also showed continuous positive
      associations of these CKD measures with aortic diameter, particularly at the
      distal aortic segment assessed. CONCLUSIONS: Reduced eGFR and elevated
      albuminuria were independently associated with greater incidence of AAA and
      greater abdominal aortic diameter. Our results suggest the potential usefulness
      of CKD measures to identify persons at high risk of AAA and the need to
      investigate pathophysiological pathways linking CKD to AAA.

PMID- 30290963
TI  - Epigenetic processing in cardiometabolic disease.
AB  - Albeit a consistent body of evidence supports the notion that genes influence
      cardiometabolic features and outcomes, the "non-genetic regulation" of this
      process is gaining increasing attention. Plastic chemical changes of DNA/histone
      complexes - known as epigenetic changes - critically determine gene activity by
      rapidly modifying chromatin accessibility to transcription factors. In this
      review, we describe the emerging role of chromatin modifications as fine tuners
      of gene transcription in adipogenesis, insulin resistance, macrophage
      polarization, immuno-metabolism, endothelial dysfunction and metabolic
      cardiomyopathy. Epigenetic processing participates in the dynamic interplay among
      different organs in the cardiometabolic patient. DNA methylation and post
      translational histone modifications in both visceral and subcutaneous adipose
      tissue enable the transcription of genes implicated in lipo- and adipogenesis,
      inflammation and insulin resistance. Along the same line, complex networks of
      chromatin modifying enzymes are responsible for impaired nitric oxide
      bioavailability and defective insulin signalling in the vasculature, thus leading
      to reduced capillary recruitment and insulin delivery in the liver, skeletal
      muscle and adipose tissue. Furthermore, changes in methylation status of IL-4,
      IFNgamma and Forkhead box P3 (Foxp3) gene loci are crucial for the polarization
      of immune cells, thus leading to adipose tissue inflammation and atherosclerosis.
      Cell-specific epigenetic information could advance our understanding of
      cardiometabolic processes, thus leading to individualized risk assessment and
      personalized therapeutic approaches in patients with cardiometabolic
      disturbances. The development of new chromatin modifying drugs indicates that
      targeting epigenetic changes is a promising approach to reduce the burden of
      cardiovascular disease in this setting.

PMID- 30290964
TI  - [Acquisition of clinical observation skills by medical students improves with
      discipline-based teaching. The example of neurological examination].
AB  - INTRODUCTION: Since 2014-2015, practical teaching of clinical observation skills
      for 2nd year medical students at our faculty has been discipline-based;
      previously, each clinical lecturer had to cover all medical fields. We assessed
      the impact of this teaching reform on the neurological examination skills of
      medical students in a before-and-after study. METHODS: Pre-reform 3rd and post
      reform 2nd and 3rd year medical students (n=62, n=71 and 52, respectively) had to
      perform 7 neurological examination items, for which performance criteria had been
      pre-defined. Subsequently, we assessed whether the mean grade in neurological
      examination skills during the test at the end of the 2nd year was different
      between students who had received neurological teaching from a neurologist (n=29)
      or another specialist (n=102). RESULTS: The median [interquartile range] number
      of items acquired by post-reform 3rd year students (4 [2-5]) was higher than that
      of pre-reform 3rd year students (2 [1-3]; P<0.001), but lower than that of post
      reform 2nd year students (5 [4-6]; P=0.01). The mean grade obtained during the
      practical test was not different in students trained by a neurologist or another
      specialist. CONCLUSION: Acquisition of neurological examination skills improved
      after the teaching reform which consisted of: (1) a discipline-based practical
      teaching of clinical observation skills; (2) a training of clinical lecturers to
      teach a limited list of educational objectives; and (3) the introduction of a
      practical test at the end of the 2nd year of medical studies. However, there was
      a decline in clinical observation skills between 2nd and 3rd year medical
      students.

PMID- 30290965
TI  - Reconstruction of anthropogenic 129I temporal variation in the Japan Sea using a
      coral core sample.
AB  - The anthropogenic long-lived radionuclide 129I is receiving increased attraction
      as a new oceanic tracer in addition to usage as a fingerprint of radionuclide
      contamination of the marine environment. To demonstrate the robustness of 129I as
      an oceanic tracer in the Northwest Pacific area, specifically in the Japan Sea,
      the input history of 129I to surface seawater was reconstructed using a
      hermatypic coral core sample from Iki Island in the Tsushima strait. Iodine
      isotopes in each annual band were measured using AMS and ICP-MS after appropriate
      pre-treatments of small amounts of coral powder. The 129I/127I ratios in the
      1940s were almost at background levels (<1 * 10-11) and increased abruptly in the
      early 1950s. Thereafter, the ratios continuously increased with some
      fluctuations; the maximum ratio, 7.13 +/- 0.72 * 10-11, being found in the late
      1990s. After that period, the ratios remained nearly constant until the present
      time (2011). The 129I originated mainly from the nuclear weapons testings of the
      1950s and the early 1960s, and from airborne releasing by nuclear reprocessing
      facilities. The dataset obtained here was used to construct a simple model to
      estimate the diffusion coefficient of 129I in the Japan Sea. The 129I/236U ratios
      over the observation period were also reconstructed to help constraining sources
      of 129I to the marine environment. Based on the results, the 129I/236U ratio
      obtained here could be an endmember of the water mass in the Kuroshio Current
      area of the Northwest Pacific Ocean.

PMID- 30290966
TI  - Retinal nerve fiber layer thickness in optic neuritis with MOG antibodies: A
      systematic review and meta-analysis.
AB  - This meta-analysis aimed to systematically review current literature measuring
      the thickness of retinal nerve fiber layer (RNFL) in patients with myelin
      oligodendrocyte glycoprotein antibodies (MOG-ab) associated optic neuritis. Ten
      studies were enrolled and the results showed that the degree of RNFL loss in MOG
      ab-positive optic neuritis patients may not differ from that of AQP4-ab patients.
      However, patients who were positive for MOG-ab showed more severe RNFL loss than
      those who were seronegative.

PMID- 30290967
TI  - Corrigendum to "Antibody-based immunotherapy of acyclovir resistant ocular herpes
      simplex virus infection" [Virology 512 (2017) 194-200].

PMID- 30290968
TI  - The psychobiology of using automated driving systems: A systematic review and
      integrative model.
AB  - Using vehicles with engaged automated driving systems (ADS) ('highly automated
      driving', HAD) will substantially impact on future society's mobility, yet the
      current understanding of human psychobiology related to HAD is still limited.
      Hence, we synthesized evidence on the psychobiology of subjects using HAD,
      informing an integrative model of the psychobiology of HAD, and providing
      guidance for reporting future research on this topic. We included (non
      )randomized studies assessing human peripheral biology markers of in-vehicle
      users in real or simulated driving environments, using vehicles with vs. without
      engaged ADS, published in English until April 2018. We systematically searched
      Web of Science, SCOPUS, and PubMed. The search consisted of a combination of
      terms describing HAD and psychobiological parameters. Risk of bias was assessed
      regarding randomization, blinding, incomplete outcome data, selective outcome
      reporting, and other potential causes. We extracted data using predefined data
      fields. Four out of five studies included in this review (N = 194 subjects)
      reported associations of use of vehicles with vs. without engaged ADS with
      various psychobiological parameters, including heart rate, respiratory sinus
      arrhythmia (RSA), indicators of electrodermal activity (EDA), and masseter
      electromyography (EMG). Heart rate tended to be reduced during HAD along with
      increased EDA and EMG, with no clear indication for changes in RSA. We cannot
      exclude substantial risk of bias, among others because the status of engagement
      of ADS was mostly non-randomized. Yet, findings suggest that HAD goes along with
      tractable changes in peripheral biology. Informed by the conceptual endophenotype
      approach (Hellhammer et al., 2018, Psychoneuroendocrinology), we propose the
      Embodied Driving (EMBODD) model that describes how HAD reshapes vehicle use
      experience, and highlight how to make future ADS equipped vehicles successful
      regarding user's health. Based on the review, we suggest reporting guidelines for
      future research on the psychobiology of HAD.

PMID- 30290969
TI  - Suspicion of acute appendicitis in adults. The value of ultrasound in our
      hospital.
AB  - OBJECTIVE: To evaluate the accuracy of ultrasonography for the diagnosis of acute
      appendicitis in adults, to calculate the negative appendicectomy rate in operated
      patients and the accuracy of pre-defined diagnostic categories and to identify
      statistically significant signs and symptoms of acute appendicitis in
      ultrasonography. MATERIAL AND METHODS: Descriptive prospective study in which we
      collected the findings of the urgent ultrasonographies ordered in a one-year
      period for adult patients with pain in the right iliac fossa (RIF), along with
      their symptoms. We classified them in 5 different diagnostic categories presented
      in the radiological report: normal appendix, non-visible appendix and no
      secondary signs, non-conclusive, probable appendicitis, certain appendicitis. By
      mean of the Stata14 software descriptive analysis, T-test and Chi-square were
      performed and the data were compared with the final pathological report. RESULTS:
      Population: 139 patients (45% men, 55% women), mean age: 32,68 (15-84).
      Prevalence of acute appendicitis: 50,35% (70/139). Negative appendicectomy rate:
      0%. Negative predictive value for the categories 1,2 and 3 taken together:
      90,78%. Positive predictive value for the categories 4 and 5 taken together:
      100%. Ultrasound sensibility and specificity 90% and 100%, respectively.
      Statistically significant signs and symptoms (p<0.05): RIF pain, fever,
      leukocytosis, left shift, visible appendix, non-compressibility, hyperechogenic
      fat, appendicolith and free fluid. CONCLUSION: Ultrasound is very accurate for
      the diagnosis of acute appendicitis in adults.

PMID- 30290970
TI  - Metastatic melanoma-asociated poliosis.

PMID- 30290971
TI  - Doege-Potter syndrome: What hypoglycemia hid.

PMID- 30290972
TI  - The chronic intestinal pseudo-obstruction subtype has prognostic significance in
      patients with severe gastrointestinal dysmotility related intestinal failure.
AB  - BACKGROUND & AIMS: Severe gastrointestinal dysmotility (GID) is a significant
      cause of chronic intestinal failure (CIF) with unclear benefits of sub
      classifying into Chronic Intestinal Pseudo-obstruction (CIPO) and non-CIPO sub
      types. We compared outcomes between CIPO and non-CIPO sub-types in a tertiary
      cohort of patients with CIF resulting from severe GID. METHODS: Adults with
      primary GID, commenced on home parenteral nutrition (HPN) over a 16-year period
      at a national referral centre, were included. All patients satisfied GID clinical
      criteria which mandated evidence of small bowel involvement either objectively
      (abnormal antroduodenal manometry) or pragmatically (failure to progress on small
      bowel feeding). Clinical outcomes including HPN dependency and survival were
      compared between CIPO and non-CIPO sub-types. RESULTS: Patients with primary GID
      requiring HPN (n = 45, age 38 +/- 2, 33 females, 23/45 (51%) CIPO, 22/45 (49%)
      non-CIPO) were included. Patients with CIPO had more surgical interventions (P =
      0.03), higher incidence of bacterial overgrowth (P = 0.006), greater parenteral
      energy (P = 0.02) and volume requirements (P = 0.05). Overall, during a mean 6
      years' follow-up, 36/45 (80%) patients remained HPN dependent. Multivariate
      analyses confirmed that the non-CIPO sub-type (P = 0.04) and catheter related
      blood stream infections/1000 days (P = 0.01) were predictive factors for time to
      discontinuing HPN. Overall 5-year survival on HPN was 85%, with no difference
      between sub-types (P = 0.83). CONCLUSIONS: The CIPO sub-type is associated with
      higher HPN dependency and should be recognized as a separate entity in severe
      GID. In multidisciplinary settings with continuous close monitoring of risks and
      benefits, our data confirm HPN is a safe, life-preserving therapy in severe GID
      related CIF.

PMID- 30290973
TI  - An internet-based approach for lifestyle changes in patients with NAFLD: Two-year
      effects on weight loss and surrogate markers.
AB  - BACKGROUND & AIMS: Interventions aimed at lifestyle changes are pivotal for the
      treatment of non-alcoholic fatty liver disease (NAFLD), and web-based programs
      might help remove barriers in both patients and therapists. METHODS: In the
      period 2010-15, 716 consecutive NAFLD cases (mean age, 52; type 2 diabetes, 33%)
      were treated in our Department with structured programs. The usual protocol
      included motivational interviewing and a group-based intervention (GBI), chaired
      by physicians, dietitians and psychologists (five weekly meetings, n = 438).
      Individuals who could not attend GBI entered a web-based intervention (WBI, n =
      278) derived from GBI, with interactive games, learning tests, motivational
      tests, and mail contacts with the center. The primary outcome was weight loss
      >=10%; secondary outcomes were alanine aminotransferase within normal limits,
      changes in lifestyle, weight, alanine aminotransferase, and surrogate markers of
      steatosis and fibrosis. RESULTS: GBI and WBI cohorts had similar body mass index
      (mean, 33 kg/m2), with more males (67% vs. 45%), younger age, higher education,
      and more physical activity in the WBI group. The two-year attrition rate was
      higher in the WBI group. Healthy lifestyle changes were observed in both groups
      and body mass index decreased by almost two points;the 10% weight target was
      reached in 20% of WBI cases vs. 15% in GBI (not significant). In logistic
      regression analysis, after adjustment for confounders and attrition rates, WBI
      was not associated with a reduction of patients reaching short- and long-term 10%
      weight targets. Liver enzymes decreased in both groups, and normalized more
      frequently in WBI. Fatty liver index was reduced, whereas fibrosis remained
      stable (NAFLD fibrosis score) or similarly decreased (Fib-4). CONCLUSION: WBI is
      not less effective than common lifestyle programs, as measured by significant
      clinical outcomes associated with improved histological outcomes in NAFLD.
      eHealth programs may effectively contribute to NAFLD control. LAY SUMMARY: In
      patients with non-alcoholic fatty liver disease, participation in structured
      lifestyle programs may be jeopardized by job and time constraints. A web-based
      intervention may be better suited for young, busy patients, and for those living
      far from liver units. The study shows that, following a structured motivational
      approach, a web-based, interactive intervention coupled with six-month face-to
      face meetings is not inferior to a standard group-based intervention with respect
      to weight loss, adherence to healthy diet and habitual physical activity,
      normalization of liver enzymes, and stable surrogate markers of fibrosis.

PMID- 30290974
TI  - A network view on brain regions involved in experts' object and pattern
      recognition: Implications for the neural mechanisms of skilled visual perception.
AB  - Skilled visual object and pattern recognition form the basis of many everyday
      behaviours. The game of chess has often been used as a model case for studying
      how long-term experience aides in perceiving objects and their spatio-functional
      interrelations. Earlier research revealed two brain regions, posterior middle
      temporal gyrus (pMTG) and collateral sulcus (CoS), to be linked to chess experts'
      superior object and pattern recognition, respectively. Here we elucidated the
      brain networks these two expertise-related regions are embedded in, employing
      resting-state functional connectivity analysis and meta-analytic connectivity
      modelling with the BrainMap database. pMTG was preferentially connected with
      dorsal visual stream areas and a parieto-prefrontal network for action planning,
      while CoS was preferentially connected with posterior medial cortex and
      hippocampus, linked to scene perception, perspective-taking and navigation.
      Functional profiling using BrainMap meta-data revealed that pMTG was linked to
      semantic processing as well as inhibition and attention, while CoS was linked to
      face and shape perception as well as passive viewing. Our findings suggest that
      pMTG subserves skilled object recognition by mediating the link between object
      identity and object affordances, while CoS subserves skilled pattern recognition
      by linking the position of individual objects with typical spatio-functional
      layouts of their environment stored in memory.

PMID- 30290975
TI  - [High-risk neuroblastoma treatment strategy: The experience of the SIOPEN group].
AB  - High-risk neuroblastoma comprises nearly half of cases of neuroblastoma and the
      long-term survival is less than 50% despite complex and intensive treatments.
      Studies conducted in Europe and in North America in the last two decades have
      identified a strategy based on four therapeutic phases: an intensive induction
      therapy, a local control by surgery and radiation, a consolidation phase with
      single or tandem high dose chemotherapy and autologous transplant, and
      immunotherapy to eliminate residual disease. Future treatment improvements are
      based on progress at each of these therapeutic steps and ultimately a better
      stratification of the strategy adapted to the type of risk. A more extensive
      tumor molecular profiling at diagnosis and relapse will help to develop new
      therapeutics and to guide risk-based strategies. Earlier use of immunotherapy and
      identification of more effective combinations in induction or in maintenance
      treatment, identification of indications of more intense consolidations using
      high-dose chemotherapy combined or not with metabolic irradiation by 131I-MIBG
      and the introduction of other targeted treatments are tracks being explored.

PMID- 30290976
TI  - Consumption of processed and pickled food and esophageal cancer risk: A
      systematic review and meta-analysis.
AB  - Previous investigations yielded inconsistent results for association of
      esophageal cancer (EC) risk and intake of processed food (including pickled food)
      or pickled food alone. The aim of this study was to perform a systematic review
      and meta-analysis of data exploring association of EC risk and intake of
      processed food (including pickled food) or pickled food alone. We systematically
      searched on PubMed and Web of Science for association of EC risk and intake of
      processed and pickled food published from 1964 to April 2018. We computed the
      multivariate odd ratio (OR) or relative risk (RR) and 95% confidence intervals
      (CI), comparing the highest and the lowest categories of processed or pickled
      food intake. The present meta-analysis showed that the highest categories of
      processed food intake were associated with a 78% increase in EC risk compared
      with the lowest categories. In addition, meta-analysis results indicated that the
      combined OR/RRs (95%CI) of studies comparing the highest and lowest categories
      were 2.10 (1.64-2.69) for pickled food. Subgroup study indicated significant
      positive associations between EC risk and intake of processed food or pickled
      food in case-control studies (combined ORs: processed food: 1.93 (95%CI: 1.66
      2.24), pickled food: 2.28 (95%CI: 1.93-2.70)), whereas no significant
      associations were detected between them in cohort studies (combined RRs:
      processed food: 1.24 (95%CI: 0.98-1.58), pickled food: 1.43 (95%CI: 0.85-2.42)).
      In conclusion, this study suggests that both a high consumption of processed and
      pickled food may increase the EC risk.

PMID- 30290977
TI  - Reversible psychiatric adverse effects related to deep brain stimulation of the
      anterior thalamus in patients with refractory epilepsy.
AB  - OBJECTIVE: Anterior nucleus of thalamus (ANT) deep brain stimulation (DBS) is
      becoming a more common treatment for drug-resistant epilepsy. Epilepsy and
      depression display a bidirectional association. Anterior nucleus of thalamus has
      connections to anterior cingulate cortex and orbitomedial prefrontal cortex,
      hence, a possible role in emotional and executive functions, and thus, ANT DBS
      might exert psychiatric adverse effects. Our aim was to evaluate previous and
      current psychiatric symptoms in patients with epilepsy undergoing ANT DBS surgery
      and assess the predictability of psychiatric adverse effects. Programming-related
      psychiatric adverse effects are also reported. METHOD: Twenty-two patients with
      ANT DBS for retractable epilepsy were examined, and a psychiatric evaluation of
      depressive and other psychiatric symptoms was performed with Montgomery and
      Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), and
      Symptom Checklist prior to surgery, concentrating on former and current
      psychiatric symptoms and medications. The follow-up visit was one year after
      surgery. RESULTS: At the group level, no changes on mood were observed during ANT
      DBS treatment. Two patients with former histories of depression experienced
      sudden depressive symptoms related to DBS programming settings; these were
      quickly alleviated after changing the stimulation parameters. In addition, two
      patients with no previous histories of psychosis gradually developed clear
      paranoid and anxiety symptoms that also relieved slowly after changing the
      programming settings. CONCLUSION: The majority of our ANT DBS patients did not
      experience psychiatric adverse effects. Certain DBS parameters might predispose
      to sudden depressive or slowly manifesting paranoid symptoms that are reversible
      via programming changes.

PMID- 30290978
TI  - Efficacy and Safety of Micropulse(r) Transscleral Cyclophotocoagulation in
      Glaucoma.
AB  - OBJECTIVE: To report the results using Micropulse(r) transscleral
      cyclophotocoagulation (Iridex) in the treatment of glaucoma. METHODS:
      Retrospective study in adult patients with glaucoma with at least 6 months of
      follow-up, and only one session of Micropulse(r). The same surgical technique was
      used in all cases. The only laser parameter that could vary was the total
      treatment duration (in seconds). The remaining parameters were fixed at 2 Watts
      of power and 0.5ms (31.3%) of active cycle. RESULTS: A total of 22 eyes of 17
      patients with glaucoma of various types and stages were included (mainly
      congenital and pseudoexfoliation). The mean follow-up time was 7.9 months. The
      total treatment duration varied from 100 to 180seconds. Definition of success:
      5mmHg <Intraocular pressure (IOP)<21mmHg and a reduction of >=20% of the baseline
      value and no addition of oral carbonic anhydrase inhibitors, and no re-operation.
      The overall success rate was 72.7% in the first month, 54% at 4 months, 41% at 6
      months, and 27.3% at final follow-up. Patients with longer treatment durations
      (180s) achieved better results. The mean reduction in IOP in successful eyes was
      36% (from 26.3 to 16.7mmHg, SD 4.58, P=.028). No complications were reported.
      CONCLUSIONS: In a heterogeneous population of glaucoma (mostly congenital and
      pseudoexfoliation types), a low success rate (27.3%) was obtained in the medium
      term with a single session of Micropulse(r).

PMID- 30290979
TI  - Choroidal neovascularisation associated with optic nerve head drusen: Case report
      and review of literature.
AB  - A 21-year-old man was seen for follow-up of optic nerve head drusen (ONHD) in the
      ophthalmology department. Funduscopy revealed the presence of choroidal
      neovascularisation (CNV) in the papillomacular bundle of his right eye (RE). The
      patient was successfully treated with two intravitreal injections of anti
      vascular endothelial growth factor (anti-VEGF). Peri-papillary choroidal
      neovascularisation in papillomacular bundle is a rare complication in patients
      with ONHD. These forms of CNV show a good response to anti-VEGF treatment.

PMID- 30290980
TI  - Missed Opportunities for HIV Screening Among a Cohort of Adolescents With
      Recently Diagnosed HIV Infection in a Large Pediatric Hospital Care Network.
AB  - PURPOSE: Routine human immunodeficiency virus (HIV) screening reduces HIV
      progression and transmission. Our aims were to determine prevalence and factors
      associated with prior HIV screening among a cohort of youth living with HIV.
      METHODS: Retrospective chart review of youth living with HIV aged 14-26 at an HIV
      clinic comparing characteristics between those with and without HIV screening
      within the year prior to diagnosis RESULTS: Subjects (n = 301) were male (85%),
      African-American (87%), and men who have sex with men (84%). Subjects seen 1 year
      prior to diagnosis (n = 58) contributed 179 visits for missed opportunities with
      59% having a documented sexual history in the electronic health record and 48%
      tested for HIV. Subjects with symptoms suggesting acute HIV infection (51%) were
      more likely to be tested (p = .04). In the adjusted model, documentation of
      sexual history and demographic factors was not associated with prior testing.
      CONCLUSION: We identified high rates of missed opportunities for HIV testing and
      sexual history documentation in the year prior to diagnosis, underscoring the
      need for routine HIV screening in adolescents.

PMID- 30290981
TI  - Equivalent dose calculation in simulation of lung cancer treatment and analysis
      of dose distribution profile.
AB  - Currently, lung cancer is one of the most lethal types of cancer (IARC, 2012),
      the pathology being detected in advanced stage, when the tumor has considerable
      volume because the disease in most cases asymptomatic in the early stages (INCA,
      2016). Dosimetry analysis of healthy organs under real conditions is not
      feasible. Therefore, computational simulations are used to aid in dose
      verification in organs of patients submitted to radiotherapy. The goal of this
      study was to calculate the equivalent dose, due to photons, in the surrounding of
      healthy organs of patients submitted to radiotherapy for lung cancer, through
      computational modeling. The simulation was performed using the MCNPX code (MNCPX,
      2006), Rex and Regina phantoms (ICRP 110, 2009), radiotherapy room, Siemens Oncor
      Expression accelerator operating at 6 MV and treatment protocol adopted at the
      INCA (National Cancer Institute - Brazil). The results obtained, considering the
      dose due to photons for both phantoms indicate that organs located inside the
      thoracic cavity received higher dose, being the bronchi, heart and esophagus more
      affected, due to their anatomical positioning. Clinical data describe the
      development of bronchiolitis, esophagitis and cardiomyopathies with decreased
      cardiopulmonary function as one of the major effects of lung cancer treatment. In
      the Regina phantom, the second largest dose was in the region of the breasts with
      615.73 mSv/Gy, while in the Rex the dose was 514.06 mSv/Gy, event related to the
      difference of anatomical structure of the organ. A qualitative analysis was
      performed between the dose deposition profile of the treatment planning system
      and the simulated treatment through the tmesh command and a similar profile of
      dose distribution was verified throughout the patient's body.

PMID- 30290982
TI  - An Input-Specific Orphan Receptor GPR158-HSPG Interaction Organizes Hippocampal
      Mossy Fiber-CA3 Synapses.
AB  - Pyramidal neuron dendrites integrate synaptic input from multiple partners.
      Different inputs converging on the same dendrite have distinct structural and
      functional features, but the molecular mechanisms organizing input-specific
      properties are poorly understood. We identify the orphan receptor GPR158 as a
      binding partner for the heparan sulfate proteoglycan (HSPG) glypican 4 (GPC4).
      GPC4 is enriched on hippocampal granule cell axons (mossy fibers), whereas
      postsynaptic GPR158 is restricted to the proximal segment of CA3 apical dendrites
      receiving mossy fiber input. GPR158-induced presynaptic differentiation in
      contacting axons requires cell-surface GPC4 and the co-receptor LAR. Loss of
      GPR158 increases mossy fiber synapse density but disrupts bouton morphology,
      impairs ultrastructural organization of active zone and postsynaptic density, and
      reduces synaptic strength of this connection, while adjacent inputs on the same
      dendrite are unaffected. Our work identifies an input-specific HSPG-GPR158
      interaction that selectively organizes synaptic architecture and function of
      developing mossy fiber-CA3 synapses in the hippocampus.

PMID- 30290983
TI  - Evaluation of Glucomannan Powder as an Ultrasound Transmission Gel Alternative
      for Resource-Constrained Environments: A Prospective, Comparative Study.
AB  - INTRODUCTION: Resource and logistical constraints may limit the availability of
      commercial ultrasound (US) transmission gel (USTG) in austere environments.
      Glucomannan powder, a dietary fiber supplement, can be mixed with tap water to
      form a gel that may be a field-expedient substitute for USTG. We compared
      glucomannan gel with a commercial USTG for US image adequacy and quality.
      METHODS: A single clinician obtained 193 US video clips from 14 different
      examinations on live-tissue and simulation training models using both commercial
      and glucomannan USTGs. Four US fellowship-trained providers, blinded to type of
      gel used, independently reviewed the randomized US video clips. The primary
      outcome of US image adequacy was scored as "yes" or "no" and analyzed using
      Pearson chi2 analysis. The secondary outcome of image quality was rated on a 0 to
      5 Likert scale and analyzed with the independent t test. RESULTS: For US image
      adequacy, commercial USTG was superior to glucomannan gel (P=0.042, 95% CI: 96.5
      96.6%), with commercial USTG adequate in 96.6% of images (375 of 388 "yes"),
      whereas glucomannan USTG was adequate in 93.5% (359 of 384 "yes") of images. For
      US image quality there was no statistically significant difference between the 2
      USTGs (P=0.176, 95% CI: 93.4-93.5%), with commercial USTG rated at 3.4+/-1.0 and
      glucomannan gel at 3.3+/-1.1. CONCLUSION: Despite a high image adequacy rate,
      glucomannan gel proved inferior to commercial USTG for US image adequacy but
      produced equivalent image quality. Glucomannan USTG may be a reasonable
      substitute when commercial USTG is unavailable.

PMID- 30290984
TI  - Outcomes of left trisectionectomy and right hepatectomy for perihilar
      cholangiocarcinoma.
AB  - BACKGROUND: Right hepatectomy (RH) is the standard surgical procedure for
      perihilar cholangiocarcinoma (PHC) with right-sided predominance in many centers.
      Although left trisectionectomy (LT) is aggressively performed for PHC with left
      sided predominance in high-volume centers, the surgical and survival outcomes of
      LT are unclear. Therefore, this study aimed to compare the outcomes of LT and RH
      for PHC. METHODS: Consecutive patients who underwent surgical resection for PHC
      at Chiba University Hospital from 2008 to 2016 were retrospectively reviewed. The
      outcomes of patients with PHC who underwent LT were compared with those who
      underwent RH following one-to-one propensity score matching. RESULTS: Of 171
      consecutive PHC resection patients, 111 were eligible for the study; 41 (37%)
      underwent LT, and 70 (63%) underwent RH. In a matched cohort (LT: n = 27, RH: n =
      27), major complication rates (67% vs. 52%; p = 0.42), 90-day mortality rates
      (15% vs. 0%; p = 0.11) and R0 resection rates (56% vs. 44%; p = 0.58) were
      similar in both groups. The 3-year recurrence-free survival rates (27% vs. 47%; p
      = 0.27) and overall survival rates (45% vs. 60%; p = 0.17) were also similar in
      both groups. CONCLUSIONS: In patients with PHC, LT could achieve similar surgical
      and survival outcomes as RH.

PMID- 30290985
TI  - [Place of partial nephrectomy assisted by robot: Review of the literature at the
      time of a request for a specific nomenclature].
AB  - INTRODUCTION: Robot-assisted surgery is practiced more and more frequently in
      urology. Besides its place in prostatectomy for cancer, it also concerns partial
      nephrectomy (NP), in the treatment of renal tumors. The objective of this review
      is to compare the robot-assisted approach with laparoscopic or open approaches in
      partial nephrectomy in terms of functional or oncological outcomes and per- and
      postoperative complications. MATERIAL AND METHODS: A systematic review of the
      literature published from 2009 was carried out on PubMed. Clinical studies or
      meta-analyzes comparing robot-assisted surgery versus laparoscopic or open
      surgery in the NP domain were used. RESULTS: The clinical data presented in this
      review of the literature are based mainly on meta-analyzes of comparative
      studies. Patients operated with robotic assistance (NPAR) had significantly fewer
      postoperative complications than patients operated by open (RR 0.61; P=0.0002) or
      laparoscopic surgery (RR 0.84; P=0.007). Positive margins, at equivalent
      pathological stages, are comparable to the open and appear to be lower than the
      laparoscopic surgery (RR 0.53; P<0.001). After NP, the change in postoperative
      glomerular filtration rate (GFR) appears to be identical between the 3 pathways.
      Hot ischemia time is significantly shorter for NPAR compared to NPL. Finally, the
      estimated blood loss and length of stay are less severe in patients operated by
      NPAR compared to those operated by open surgery. CONCLUSION: Robot-assisted
      surgery offers the same oncological results (in the short and medium term) and
      appears to improve functional outcomes and morbidity. However, these findings
      need to be carefully analyzed, due to the low level of evidence from the studies
      presented and included in the meta-analyzes, and the lack of randomized clinical
      studies.

PMID- 30290986
TI  - Professional advancement, performance, and injury characteristics of baseball
      players entering the Major League Baseball draft after treatment for shoulder
      injuries.
AB  - BACKGROUND: How shoulder injuries treated before the Major League Baseball (MLB)
      draft affect the player's performance over their career is unclear. The purpose
      of this study was to determine whether prior shoulder injuries were associated
      with a difference in the level of performance and advancement of MLB draftees.
      METHODS: Before entering the draft, 119 professional baseball players from 2004
      to 2010 were treated for a shoulder injury (73% treated surgically) as an
      amateur. A 3:1 matched case-control was performed to players without prior
      shoulder injuries by age, position, round selected, and signing bonus. Follow-up
      data were collected in 2016, and professional advancement, disabled list time,
      and in-game performance statistics for pitchers were analyzed and compared.
      RESULTS: Players with a prior shoulder injury had a statistically higher chance
      to be assigned to the disabled list then controls (P = .03), but there was no
      difference in disabled list time or professional advancement. Pitchers with a
      prior shoulder injury pitched a statistically lower number of innings per game
      than controls (P = .04). All other in-game performance statistics were not
      statistically different. The type of treatment did not have any effect on future
      performance or advancement. CONCLUSIONS: Professional baseball players treated
      for prior shoulder injuries at the amateur level were more likely to sustain
      future disability than their matched controls, but it did not affect professional
      advancement.

PMID- 30290987
TI  - Blasted Hopes and Wasted Dreams.

PMID- 30290988
TI  - Discovery of a novel series of pyridine and pyrimidine carboxamides as potent and
      selective covalent inhibitors of Btk.
AB  - Btk is an attractive target for the treatment of a range of Bcell malignancies as
      well as several autoimmune diseases such as murine lupus and rheumatoid
      arthritis. Several covalent irreversible inhibitors of Btk are currently in
      development including ibrutinib which was approved for treatment of B-cell
      malignancies. Herein, we describe our efforts using X-ray guided structure based
      design (SBD) to identify a novel chemical series of covalent Btk inhibitors. The
      resulting pyridine carboxamides were potent and selective inhibitors of Btk
      having excellent enzymatic and cellular inhibitory activity.

PMID- 30290989
TI  - Ferrocene-based inhibitors of hepatitis C virus replication that target NS5A with
      low picomolar in vitro antiviral activity.
AB  - An unprecedented series of organometallic HCV (hepatitis C virus) NS5A
      (nonstructural 5A protein) replication complex inhibitors that incorporates a
      1,1'-ferrocenediyl scaffold was explored. This scaffold introduces the elements
      of linear flexibility and non-planar topology that are unconventional for this
      class of inhibitors. Data from 2-D NMR spectroscopic analyses of these complexes
      in solution support an anti (unstacked) arrangement of the pharmacophoric groups.
      Several complexes demonstrate single-digit picomolar in vitro activity in an HCV
      genotype-1b replicon system. One complex to arise from this investigation (10a)
      exhibits exceptional picomolar activity against HCV genotype 1a and 1b replicons,
      low hepatocellular cytotoxicity, and good pharmacokinetic properties in rat.

PMID- 30290990
TI  - Low microRNA-139 expression associates with poor prognosis in patients with
      tumors: A meta-analysis.
AB  - BACKGROUND: microRNA-139 (miR-139) is dysregulated in various types of tumors and
      plays a key role in carcinogenesis. miR-139 may be used as a diagnostic and
      prognostic biomarker of cancers. However, the data from the literature are not
      consistent. The present study aimed to verify the prognostic and diagnostic
      values of miR-139 in solid tumors. DATA SOURCES: PubMed, Web of Science and
      Embase databases were searched and publications from January 2011 to August 2017
      were included. We used Gene Expression Omnibus (GEO) and The Cancer Genome Atlas
      (TCGA) database to further validate this meta-analysis. RESULTS: Eight individual
      studies from seven articles were included. Pooled analyses showed that low miR
      139 expression was related to worse overall survival (OS) [hazard ratio (HR) =
      2.27; 95% confidence intervals (CI): 1.74-2.95; P < 0.001] in solid tumors,
      including hepatocellular carcinoma (HCC) and glioblastoma multiforme (GBM),
      consisting with the results of TCGA. However, our results of CRC showed that low
      miR-139 expression was associated with poor OS which was contradictory with the
      results in TCGA database and need larger samples to validate the phenomenon;
      whereas for CRC patients, high miR-139 expression predicted poor RFS, which was
      in good accordance with TCGA results. The results of 27 microarrays from GEO
      database showed that miR-139 expression levels were lower in tumor tissues
      compared to adjacent non-tumor tissues or healthy tissues. Decreased miR-139
      expression was also significantly correlated with poor differentiation grade (OR
      = 3.57; 95% CI: 1.44-8.85; P = 0.006). However, the combined data indicated that
      no associations between miR-139 expression and the following parameters such as
      age (pooled OR = 1.50; 95% CI: 0.69-3.24; P = 0.304), gender (pooled OR = 0.92;
      95% CI: 0.56-1.51; P = 0.738), tumor size (pooled OR = 1.51; 95% CI: 0.69-3.31; P
      = 0.298), late tumor-node-metastasis stage (pooled OR = 1.63; 95% CI: 0.99-2.68;
      P = 0.057) and lymph-node-metastasis (pooled OR = 0.66; 95% CI: 0.34-1.28; P =
      0.222). CONCLUSIONS: Low miR-139 expression was related to poor prognosis in HCC
      and GBM, which could be regarded as a potential prognostic biomarker. However,
      its precise functional role in CRC still need to be further investigated through
      larger samples and multicenter studies.

PMID- 30290991
TI  - Roux-en-Y gastric bypass versus sleeve gastrectomy: what factors influence
      patient preference?
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the
      most commonly performed bariatric procedures. RYGB involves altered
      gastrointestinal anatomy and 2 anastomoses, while SG involves gastric resection.
      When potential patients view images of the procedures, they may perceive RYGB to
      involve significant risk compared with SG, in which no significant
      gastrointestinal alterations are depicted. OBJECTIVE: To evaluate preferences for
      RYGB versus SG. SETTING: Survey of U.S. adults. METHODS: An electronic survey was
      distributed to 1000 U.S. adults. Respondents selected either RYGB or SG based on
      (1) procedural pictures alone, (2) only data on risks and benefits of each
      procedure, (3) pictures with corresponding risk/benefit profile, and (4) pictures
      with mismatched information. RESULTS: Overall, 999 individuals met inclusion
      criteria; 66 (7%) had undergone bariatric surgery and were excluded. Mean age and
      body mass index of respondents was 44.8 +/- 14.6 years (n = 922) and 28.7 +/- 8.0
      kg/m2 (n = 915). A higher proportion of patients preferred RYGB to SG when images
      only were provided (54% versus 46%), when information only was provided (63%
      versus 37%), and when correct information with the procedure image was provided
      (57% versus 43%). When presented with mismatched information and images, 56%
      preferred RYGB information + SG image versus SG information + RYGB image (44%).
      CONCLUSIONS: Based on this survey, providing evidence-based risks and benefits of
      a procedure resulted in the majority of respondents choosing RYGB over SG. When
      procedure images were provided alone, preference for RYGB and SG were similar.
      There are likely other factors contributing to increasing SG volume aside from
      patient preference.

PMID- 30290992
TI  - [Characteristics of patients of the Cerebral Palsy Association].
AB  - INTRODUCTION: As the life expectancy has increased in individuals with cerebral
      palsy, this has led to being able to assess the changes in the bio-psycho-social
      dimensions of their health. OBJECTIVE: The aim of the study is to describe the
      characteristics of individuals with cerebral palsy and to evaluate their
      functional situation. METHODS: Cross-sectional descriptive study conducted on a
      sample of 26 individuals between 27 and 65 years old with cerebral palsy. Data
      was collected during a semi-structured interview. The Cross Motor Function
      Classification System (GMFCS), the Manual Ability Classification System (MACS),
      and the Communication Function Classification System (CFCS), were used to
      evaluate the functional situation. RESULTS: The profile of the adult seen in the
      Cerebral Palsy Association of Burgos, Spain, is male, over 40 years old, single,
      illiterate, with no professional qualification, lives in a residence, receives
      social benefit, and with great functional disability. CONCLUSIONS: The functional
      capacity of people with cerebral palsy who are in adult care centres is low. It
      emphasises the low cultural level and the lack of professional qualification and
      all of them have a disability that limits their ability to perform daily
      activities, possibly related to the high mean age.

PMID- 30290993
TI  - [Results of an integration model between primary care and cardiology: Searching
      for efficient models].

PMID- 30290994
TI  - Evaluation of benchtop NMR Diffusion Ordered Spectroscopy for small molecule
      mixture analysis.
AB  - Diffusion Ordered Spectroscopy (DOSY) is an attractive method for analyzing
      chemical mixtures in the liquid state because it separates spectra by the
      molecular weight of the associated molecule. It has been compared with hyphenated
      chromatographic and analytical methods such LC-MS and has broad potential in
      servicing those same applications including forensics, reaction analysis, quality
      control, and fraud detection. Benchtop NMR can collect quality spectra on small
      molecules, however, lacks the chemical shift dispersion of high field
      instruments, can suffer from spectral overlap common in mixtures, and the
      diminished sensitivity of the lower field compounds these problems. In this work,
      we show that existing high field pulse sequences and processing methods perform
      well at 43 MHz. Spectra from molecular mixtures where the constituents had 20%
      differences in diffusion coefficients and significant overlap were able to be
      matched to a bespoke spectral library and identified correctly. In addition,
      spectra from mixtures with constituents that have severe overlap in the spectrum
      and differ by 50% in diffusion coefficients were also able to be match and
      identified correctly. The combination of benchtop NMR and easy implementation of
      modern pulse sequences and processing show promise of bringing these useful
      methods to chemistry laboratories in research and industrial environments.

PMID- 30290995
TI  - T1-D-T2 correlation of porous media with compressed sensing at low-field NMR.
AB  - 3D Laplace NMR can distinguish different components of confined fluid in
      sedimentary rocks, which is important to oil industry. However, the measurement
      time for such experiments is very long, which hinders the application in some
      cases such as NMR well logging. In this research, we accelerated T1-D-T2
      experiment with compressed sensing (CS) method at low-field NMR. Simulation was
      first performed to examine the CS reconstruction method. The experiments were
      subsequently implemented on a 2 MHz spectrometer (Oxford instrument), which has a
      similar magnetic field strength to well logging tool. The T1, D and T2
      information are obtained by the inversion recovery, pulsed field gradients and
      Carr-Purcell-Meiboom-Gill (CPMG) method, respectively. The subsampling is applied
      in T1 and D dimensions with pseudo-random sampling. The measurement time reduced
      from 3 h to 0.6 h with CS method and a relative error of around 5% is achieved
      for data with signal-to-noise ratio of 28. The water and oil peaks are clearly
      distinguished in the correlation maps from subsampled data. The samples with
      different oil-water ratio and glass bead volume fraction were measured to examine
      the sensitivity of this method. In addition, diffusion and relaxation properties
      of the correlation maps are discussed.

PMID- 30290996
TI  - Perfluoroalkyl substances and metabolic syndrome.
AB  - BACKGROUND: Perfluoroalkyl substances (PFAS) are a class of contaminants used in
      many industrial applications and consumer products. Certain PFAS are regulated or
      voluntarily limited due to concern about environmental persistence and adverse
      health effects. OBJECTIVES: In this analysis we examine PFAS levels and their
      association with metabolic syndrome and its components, using a representative
      sample of the U.S. POPULATION:  METHODS: Data on PFAS levels and metabolic
      syndrome components were collected from the 2007-2008, 2009-2010, 2011-2012, and
      2013-2014 cycles of the National Health and Nutrition Examination Survey. Twelve
      different PFAS were measured in serum samples from participants. Logistic
      regression models were used to identify associations between metabolic syndrome,
      its individual components, and serum PFAS concentrations. RESULTS: Over one-third
      (37%) of participants met the definition for metabolic syndrome, with increased
      waist circumference and elevated glucose being the most commonly reported
      components. Seven PFAS were detected in at least 30% of participants and were
      examined in subsequent analyses (PFDA, PFOA, PFOS, PFHxS, MPAH, PFNA, PFUnDA).
      The PFAS with the highest concentrations was PFOS (median 8.4 ng/mL), followed by
      PFOA, PFHxS and PFNA. After adjusting for potential confounders, PFNA was
      associated with increased risk of metabolic syndrome and well as several
      individual components, while the highest levels of PFHxS were associated with
      elevated triglycerides. Other PFAS were associated with decreased risk of at
      least one outcome. CONCLUSIONS: Associations between PFAS and metabolic syndrome
      are inconsistent within and across studies. PFNA was consistently associated with
      increased risk for components of the syndrome, a finding that warrants further
      investigation.

PMID- 30290997
TI  - Relation between adenoid size and otitis media with effusion.
AB  - AIMS: This study compares the efficacy of adenoidectomy on otitis media with
      effusion (OME) in patients with different size of adenoids and the connection
      between differently sized adenoids and middle ear effusion. MATERIAL AND METHODS:
      Children with a history of at least 3 months' OME underwent adenoidectomy and
      myringotomy without the insertion of a tympanostomy tube. Treatment assignment
      was stratified by adenoids' size causing choanal obstruction (grade I-III) and
      according to Eustachian tube ostium obstruction (grade A-C). The subjects were
      followed for 12 months. RESULTS: Adenoidectomy was significantly more effective
      in children with adenoids in contact with torus tubarius (grade B, C) compared to
      those with small adenoids without contact (P<0.001). The volume of the adenoids
      was irrelevant (P=0.146). The size of adenoids did not affect the viscosity of
      the middle ear secretion. The distribution of mucous and serous secretion was not
      dependent on the size of adenoids; the efficacy of adenoidectomy was 82% in
      mucous as well as serous secretion. CONCLUSION: The relation between adenoids and
      torus tubarius is more important than the volume of the adenoids. The viscosity
      of middle ear fluids (serous or mucous) did not influence the rate of treatment
      efficacy.

PMID- 30290998
TI  - Comparison of cancer diagnosis recording between the Clinical Practice Research
      Datalink, Cancer Registry and Hospital Episodes Statistics.
AB  - INTRODUCTION: The Clinical Practice Research Datalink (CPRD) is a large
      electronic dataset of primary care medical records. For the purpose of
      epidemiological studies, it is necessary to ensure accuracy and completeness of
      cancer diagnoses in CPRD. METHOD: Cases included had a colorectal,
      oesophagogastric (OG), breast, prostate or lung cancer diagnosis recorded in a
      least one of CPRD, Cancer Registry (CR) or Hospital Episodes Statistics(HES)
      between 2000 and 2013. Agreement in diagnosis between the datasets, difference in
      dates, survival at one and five-years, and whether patient characteristics
      differed according to the dataset or the timing of diagnosis were investigated.
      RESULTS: 116,769 patients were included. For each cancer, approximately 10% of
      cases identified from CPRD or HES were not confirmed in the CR. 25.5% colorectal,
      26.0% OG, 8.9% breast, 32.0% lung and 18.6% prostate cases identified from the CR
      were missing in CPRD. The diagnosis date was recorded later in CPRD compared with
      CR for each cancer, ranging from 81.1% for prostate to 59.6% for colorectal,
      especially if the diagnosis was an emergency. Compared with the CR and HES, the
      adjusted risk of a missing diagnosis in CPRD was significantly higher if the
      patient was older, had more co-morbidities or was diagnosed as an emergency.
      Survival at one and five-years was highest for CPRD. CONCLUSION: Patient
      demographics and the route of diagnosis impact the accuracy of cancer diagnosis
      in CPRD. Although CPRD provides invaluable primary care data, patients should
      ideally be identified from the CR to reduce bias.

PMID- 30290999
TI  - Surface lipidome of the lone star tick, Amblyomma americanum, provides leads on
      semiochemicals and lipid metabolism.
AB  - Lipids extracted from the surface of the lone star tick, Amblyomma americanum,
      were analyzed by high resolution mass spectrometry. Prior to lipid extraction,
      the adult ticks were either unfed or fed on cattle, and the fed ticks were in
      groups either containing males and females together, or containing only males or
      females. Cholesteryl esters were found on the surfaces of fed females, and they
      may provide a more complete description of the composition of the mounting sex
      pheromone. Dihydrocholesteryl esters were detected on the surfaces of unfed males
      and females, suggesting a possible role in survival during host-seeking.
      Dehydrodeoxyecdysone, found on fed females, could be a component of the genital
      sex pheromone. The most abundant polar surface lipids detected were
      acylglycerides. High levels of sphingolipids and glycerophospholipids on males
      fed separately might be derived, in part, from sperm development. A high level of
      a 20:4 fatty acid, presumably arachidonic acid, was found on the surface of fed
      females, indicating that it may be a component of the genital sex pheromone. A
      high level of docosenamide was found on the surface of fed females. Wax esters
      were found on the surfaces of fed ticks but not on unfed ticks. These esters
      could be involved in elasticity of the cuticle of engorged females or in wax
      coating of eggs. N-acylethanolamines were found on the surfaces of male and
      female ticks fed together, and on male ticks fed separately, but were absent or
      at low levels on females fed separately and on unfed ticks. This pattern suggests
      a possible role as a metabolic coordination primer pheromone.

PMID- 30291000
TI  - Remote Viewing of Concealed Target Pictures Under Light and Dark Conditions.
AB  - CONTEXT: The belief that performing a nonlocal task in darkness plays a
      facilitating role in remote viewing and other psi-related phenomena is well
      established in esoteric and traditional beliefs (Grim, 1983; Hallowell, 1942;
      Lyon, 2012). However, the role of darkness in RV success is unclear beyond these
      esoteric explanations. OBJECTIVE: This study explored the differential effect of
      darkness/light on remote viewing ability alongside the effect of time and their
      potential interaction. DESIGN: From an initial sample of twenty, seven remote
      viewers contributed a total of nineteen sessions each (nine light/ten dark) which
      utilised randomized target selection, free-response descriptions, and ratings by
      both participants and an independent judge. RESULTS: The usable data gave the
      edge to dark condition performance; the difference was not statistically
      significant. A statistically significant difference between remote viewer and
      independent judge raw scores attributed to the target image was identified (t
      (132) = 4.56, p <.001 (two-tailed) Mdiff = 14.21 [8.05, 20.4]) with a medium
      effect size (d = 0.40 [0.21, 0.57]). Exploratory post-hoc analyses concerning the
      numinosity of target images were conducted, to determine if this characteristic
      was associated with success. For numinosity ratings of target images, a mean
      difference of 11.24, 95% CI [0.12, 22.3] was shown as significant, with the
      target images of participant 'hit' sessions containing higher numinosity ratings
      than unsuccessful 'miss' sessions (t (11.47) = 2.22, p (two-tailed) = .048) with
      a large effect size (d = 1.02, [0.01, 1.99]). CONCLUSION: The findings may have
      implications for the use of participant judgments in future remote viewing
      research. Furthermore, because there are several advantages to what
      parapsychologists refer to as "free response" targets as opposed to "forced
      choice" targets (Honorton, 1975), the findings for target numinosity may have
      implications for the future selection of target material.

PMID- 30291001
TI  - Are self-ligating brackets' slots dimensions accurate?
AB  - OBJECTIVE: The purpose of this study is to measure the dimensions of the slot's
      top and base of passive self-ligating brackets of three commercial and available
      systems and to compare the measured dimensions with the manufacturers' published
      dimensions. METHODS: Digital microscope was used to measure the slot's top and
      base of 40 Central incisor brackets by three different manufacturers, Carriere
      SLX (Ortho Organizer, USA), Damon Q (Oramco USA) and Smart Clip (3M Unitek USA).
      The measurements were taken after the doors of all brackets were removed and
      compared with the manufacturers' claimed dimensions. RESULTS: All brackets showed
      a significant increase in dimensions from both the slot's top and base compared
      to the manufacturers' published dimensions. For the base of the bracket's slot,
      Carriere SLX brackets showed the least difference while Damon Q brackets had the
      greatest. Moreover, for the top of the bracket's slot, the Smart clip brackets
      showed the greatest difference. The percentage of difference between the actual
      measurements and the manufacturers' prescriptions shows that for the slot's base,
      Carriere SLX brackets had the smallest percentage increase by .36%, followed by
      Smart clip by 6.7% and the Damon Q brackets by 8.1%. While for the slot's top
      Carriere SLX had the smallest percentage increase by .72%, followed by Damon Q by
      12.3% increase and finally Smart Clip brackets by 12.8%. CONCLUSIONS: The actual
      measurements of passive self-ligating brackets from 3 manufacturers were larger
      than the manufacturers' published dimension. This amount of increase may affect
      the amount torque expression.

PMID- 30291002
TI  - ?

PMID- 30291003
TI  - Efficiency of colony formation and differentiation of human spermatogenic cells
      in two different culture systems.
AB  - Optimization of in vitro culture system for the expansion and the maturation of
      male germ cells to post meiotic stages is a valuable tool for studies exploring
      spermatogenesis regulation and the management of male infertility. Several
      studies have reported promising results of mouse spermatogonial stem cells
      culture in three-dimensional (3D) culture systems and a subsequent production of
      sperm. In the present study, we investigated the capacity of a three-dimensional
      soft agar culture system (SACS) supplemented with Knockout Serum Replacement
      (KSR) in colony formation and inducing human germ cells to reach post-meiotic
      stages. Testicular cells from testes of brain -dead donors were first cultured
      for three weeks in proliferation medium. The cells were subsequently cultured in
      the upper layer of the SACS (3D group) in a medium supplemented with KSR and
      hormones, and the results were compared with that of a two-dimensional (2D)
      culture system. We found that the number and diameter of colonies and the levels
      of expression of Scp3 and Integrin alpha6 in the 3D culture group were
      significantly higher than in the 2D group. Our findings indicate that SACS can
      reconstruct a microenvironment capable of regulating both proliferation and
      differentiation of cell colonies.

PMID- 30291004
TI  - The role of network ties to support implementation of a community pharmacy
      enhanced services network.
AB  - BACKGROUND: Limited evidence exists on how to integrate community pharmacists
      into team-based care models, as the inclusion of community pharmacy services into
      alternative payment models is relatively new. To be successful in team-based care
      models, community pharmacies need to successfully build relationship with diverse
      stakeholders including providers, care managers, and patients. OBJECTIVES: The
      aims of this study are to: (1) identify the role of network ties to support
      implementation of a community pharmacy enhanced services network, (2) describe
      how these network ties are formed and maintained, and (3) compare the role of
      network ties among high- and low-performing community pharmacies participating in
      an enhanced services network. METHODS: Using a semi-structured interview guide,
      we interviewed 40 community pharmacy representatives responsible for
      implementation of a community pharmacy enhanced services program. We analyzed for
      themes using social network theory to compare network ties among 24 high- and 16
      low-performing community pharmacies. RESULTS: The study found that high
      performing pharmacies had a greater diversity of network ties (e.g.,
      relationships with healthcare providers, care managers, and public health
      agencies). High-performing pharmacies were able to use those ties to support
      implementation of NC-CPESN. High- and low-performing pharmacies used similar
      strategies for establishing ties with patients, such as motivational interviewing
      and assigning staff members to be responsible for engaging high-risk patients.
      High-performing pharmacies used additional strategies such as assessing patient
      preferences to support patient engagement, increasing patient receptivity towards
      enhanced services. CONCLUSIONS: Community pharmacies may vary in their ability to
      develop relationships with other healthcare providers, care management and public
      agencies, and patients. As enhanced services interventions that require care
      coordination are scaled up and spread, additional research is needed to test
      implementation strategies that support community pharmacies with developing and
      maintaining relationships across a diverse group of stakeholders (e.g.,
      healthcare providers, care managers, public health agencies, patients).

PMID- 30291005
TI  - Dentofacial deformities and the quality of life of patients with these
      conditions: a comparative study.
AB  - OBJECTIVES: The aim of the present study was to evaluate the quality of life of
      patients with dentofacial deformities and of patients subjected to orthognathic
      surgery to compare their results with those of patients who have no dentofacial
      deformity by applying the Orthognathic Quality of Life Questionnaire (OQLQ).
      STUDY DESIGN: Three groups of patients were interviewed, and the OQLQ instrument
      was applied to them by one examiner. RESULTS: Results showed statistical
      differences between groups and suggested that patients with no deformity and
      those subjected to orthognathic surgery have better quality of life compared with
      those with facial deformity. CONCLUSIONS: Orthognathic surgery with the
      consequent dentofacial correction seems to have a positive effect on quality of
      life.

PMID- 30291006
TI  - Multiple superficial mucoceles concomitant with oral lichen planus: a case
      series.
AB  - Superficial mucoceles are a relatively rare variant of common mucoceles and have
      an unclear etiology. Clinically, they are small, translucent, subepithelial
      vesicles affecting the oral mucosa in the retromolar region, the lower labial and
      buccal regions, and the bilateral soft palate. Superficial mucocele is easily
      misdiagnosed as pemphigoid, bullous lichen planus, herpes lesion, or venous lake
      when it is concomitant with oral lichen planus (OLP) or lichenoid disorders on
      the basis of the initial impression. An inflammatory mechanism related to OLP has
      been hypothesized to induce the development of superficial mucoceles. It is
      essential to be familiar with this entity. This report presents 9 cases of
      multiple superficial mucoceles that occurred sequentially concomitant with OLP
      and with consistent clinical and histopathologic features. Relevant studies
      reported in the literature are also reviewed to provide additional clarification
      of the etiology, clinicopathologic characteristics, and differential diagnosis.

PMID- 30291007
TI  - A clinicopathologic study on central odontogenic fibroma: with special reference
      to amyloid variant.
AB  - OBJECTIVE: The aim of this study was to clarify the clinicopathologic features of
      central odontogenic fibroma (OF), especially the amyloid variant, and to discuss
      its association with the Langerhans cell variant of calcifying epithelial
      odontogenic tumor (CEOT). STUDY DESIGN: The clinicopathologic features and
      immunophenotypes of 17 OFs, including 6 amyloid variants, were analyzed. The
      Langerhans cell variant of CEOT is reviewed, and its relationship with OF is
      discussed. RESULTS: Most OFs (13 of 17) were located at the anterior region of
      the jaws, often with root resorption. The amyloid variant exhibited the typical
      clinicopathologic features of OFs, characterized by dispersed small epithelial
      nests embedded in a fibrous stroma. Immunohistochemically, the epithelial
      component in all central OFs, including the amyloid variants, exhibited dispersed
      staining for CK10/13 but was negative for CK7 and CK8/18. Langerhans cells were
      positive for S-100 and Langerin in the epithelium of OFs, including the amyloid
      variants. CONCLUSIONS: The amyloid variant of OF is a rare benign tumor
      exhibiting the typical clinicopathologic features of conventional OFs and should
      not be diagnosed as CEOT even in the presence of amyloid deposits. Previously
      reported cases described as "Langerhans cell variant of CEOT" should be
      classified as the "amyloid variant of OF," given that it shares features more in
      common with OFs than with CEOTs.

PMID- 30291008
TI  - One-year risks of stroke and mortality in patients with atrial fibrillation from
      different clinical settings: The Gulf SAFE registry and Darlington AF registry.
AB  - BACKGROUND: Differences exist in oral anticoagulation (OAC) use between different
      populations with atrial fibrillation (AF), which may be associated with varying
      outcomes. PURPOSE: We aimed to provide patient level comparisons of two cohorts
      of patients with AF, from the United Kingdom (UK) and Middle East (ME). METHODS:
      The clinical characteristics, prescription of OAC, one-year risk of stroke and
      mortality were compared between individual patients with AF included into the
      Darlington AF registry (UK, n = 2258) and the Gulf SAFE (Survey of atrial
      fibrillation events) registry (ME, n = 1740). RESULTS: A high percentage of
      patients from the Darlington registry were candidates for OAC (i.e., CHA2DS2-VASc
      score >=2 in males or >=3 in females; 82.0% in Darlington and 57.1% in Gulf
      SAFE). OAC use was suboptimal (52.0% in Darlington vs 58.4% in Gulf SAFE). One
      year rates of stroke and mortality were high in both populations, especially in
      those with CHA2DS2-VASc score >=2 in males and >=3 in females (Darlington vs.
      Gulf SAFE: 3.51% vs. 5.63 for stroke; 11.4% vs. 16.8% for mortality). On
      multivariate analyses, female sex and previous stroke were independently
      associated with stroke events; while elderly age, female sex, vascular disease
      and heart failure were independent risk factors for mortality (all p < 0.05).
      Patients from Gulf SAFE registry had higher risk of stroke (odds ratio, 2.18
      [1.47-3.23]) and mortality (odds ratio, 1.67 [1.31-2.14]) compared with those
      from Darlington registry. The CHA2DS2-VASc score showed good discrimination in
      predicting one-year risk of stroke (area under curve, 0.71 [0.65-0.76] in non
      anticoagulated patients) and mortality (area under curve, 0.70 [0.68-0.72]) in
      the whole study population, as well as in Darlington or Gulf SAFE registry
      separately. CONCLUSIONS: Stroke prevention was generally suboptimal in patient
      cohorts from the two registries, which was associated with high one-year risks of
      stroke and mortality, particularly so among patients from the Gulf SAFE registry.
      The higher risks for stroke and mortality in AF patients from the Gulf SAFE
      registry (compared to a UK cohort) merit further implementation of cardiovascular
      prevention strategies.

PMID- 30291009
TI  - Centrifugal wave-front propagation speed for localizing the atrial tachycardia
      origin.
AB  - BACKGROUND: The earliest activation site (EAS) on a centrifugally-propagated
      atrial tachycardia (AT) map may represent the true AT origin (true-focal
      pattern), or the earliest site resulting from passive activation of AT
      originating from neighboring tissue (pseudo-focal pattern). We assessed the
      benefits of using the wave-front propagation speed to distinguish between the
      true- and the pseudo-focal pattern. METHODS: AT mapping was performed using a
      novel ultra-high resolution mapping system with a 64-electrode mini-basket
      catheter. The true AT origin was defined as the site where radiofrequency
      application eliminated AT. The wave-front propagation speed was estimated from
      the area surrounded by the centrifugally-propagated wave front over a specific
      time interval. RESULTS: Total of 46 centrifugally propagated AT maps from 34
      patients were analyzed, including 18 true-focal and 28 pseudo-focal pattern. The
      area surrounded by the propagated wave front was significantly smaller for the
      true-focal pattern than for the pseudo-focal pattern, 1-20 msec after the
      earliest activation. The true-focal pattern was identified by the area 13 msec
      after the earliest activation, with the best cut-off area value of <4.5 cm2.
      CONCLUSION: The presence or absence of a true origin of AT at the EAS on
      centrifugally-propagated AT maps can be distinguished using a wave-front
      propagation speed.

PMID- 30291010
TI  - Duration and complications of diabetes mellitus and the associated risk of
      infective endocarditis.
AB  - BACKGROUND: Long duration of diabetes mellitus (DM) is associated with an
      increased risk of infection, however no studies have yet focused on the duration
      of DM and the associated risk of infective endocarditis (IE). METHODS: Patients
      with DM were identified through the Danish Prescription Registry, 1996-2015.
      Duration of DM was split in follow-up periods of: 0-5 years, 5-10 years, 10-15
      years, and >15 years. Multivariable adjusted Poisson regression was used to
      calculate incidence rate ratios (IRR) according to study groups. DM late-stage
      complications and the associated risk of IE were investigated as time-varying
      covariates using the validated Diabetes Complications Severity Index (DCSI).
      RESULTS: We included 299,551 patients with DM. In patients with DM duration of 0
      5 years, 5-10 years, 10-15 years, and >15 years, the incidence rates of IE were
      0.24, 0.33, 0.58, and 0.96 cases of IE/1000 person years, respectively. Patients
      with DM duration 5-10 years, 10-15 years, and >15 years were associated with a
      higher risk of IE with an IRR of 1.24 (95% CI: 1.02-1.51), 1.92 (95% CI: 1.52
      2.43) and 3.05 (95% CI: 2.11-4.40), respectively, compared with DM duration 0-5
      years. Patients with a DCSI score of 2, 3 and >3 were associated with a higher
      risk of IE compared with patients with a DCSI score of 0, IRR = 1.78 (95% CI:
      1.34-2.36), IRR = 2.34 (95% CI: 1.73-3.16), and IRR = 2.59 (95% CI: 1.92-3.48),
      respectively. CONCLUSION: This study shows a stepwise increase in the risk of IE
      with DM duration and severity independent of age and known comorbidity.

PMID- 30291011
TI  - Effect of Intensive Blood Pressure Lowering on Kidney Tubule Injury: Findings
      From the ACCORD Trial Study Participants.
AB  - RATIONALE & OBJECTIVE: Random assignment to intensive blood pressure (BP)
      lowering (systolic BP<120mmHg) compared to a less intensive BP target (systolic
      BP<140mmHg) in the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD
      BP) trial resulted in a more rapid decline in estimated glomerular filtration
      rate (eGFR). Whether this reflects hemodynamic effects or intrinsic kidney damage
      is unknown. STUDY DESIGN: Longitudinal analysis of a subgroup of clinical trial
      participants. SETTINGS & PARTICIPANTS: A subgroup of 529 participants in ACCORD
      BP. EXPOSURES: Urine biomarkers of tubular injury (kidney injury molecule 1,
      interleukin 18 [IL-18]), repair (human cartilage glycoprotein 39 [YKL-40]), and
      inflammation (monocyte chemoattractant protein 1) at baseline and year 2.
      OUTCOMES: Changes in eGFR from baseline to 2 years. ANALYTICAL APPROACH: We
      compared changes in biomarker levels and eGFRs across participants treated to an
      intensive versus less intensive BP goal using analysis of covariance. RESULTS: Of
      529 participants, 260 had been randomly assigned to the intensive and 269 to the
      standard BP arm. Mean age was 62+/-6.5 years and eGFR was 90mL/min/1.73m2.
      Baseline clinical characteristics, eGFRs, urinary albumin-creatinine ratios
      (ACRs), and urinary biomarker levels were similar across BP treatment groups.
      Compared to less intensive BP treatment, eGFR was 9.2mL/min/1.73m2 lower in the
      intensive BP treatment group at year 2. Despite the eGFR reduction, within this
      treatment group, ACR was 30% lower and 4 urinary biomarker levels were unchanged
      or lower at year 2. Also within this group, participants with the largest
      declines in eGFRs had greater reductions in urinary IL-18 and YKL-40 levels. In a
      subgroup analysis of participants developing incident chronic kidney disease
      (sustained 30% decline and eGFR<60mL/min/1.73m2; n=77), neither ACR nor 4
      biomarker levels increased in the intensive treatment group, whereas the level of
      1 biomarker, IL-18, increased in the less intensive treatment group. LIMITATIONS:
      Few participants with advanced baseline chronic kidney disease. Comparisons
      across treatment groups do not represent comparisons of treatment arms created
      solely through randomization. CONCLUSIONS: Among a subset of ACCORD-BP trial
      participants, intensive BP control was associated with reductions in eGFRs, but
      not with an increase in injury marker levels. These findings support that eGFR
      decline observed with intensive BP goals in ACCORD participants may predominantly
      reflect hemodynamic alterations.

PMID- 30291012
TI  - Effects of Intensive Blood Pressure Lowering on Kidney Tubule Injury in CKD: A
      Longitudinal Subgroup Analysis in SPRINT.
AB  - BACKGROUND: Random assignment to the intensive systolic blood pressure (SBP) arm
      (<120mmHg) in the Systolic Blood Pressure Intervention Trial (SPRINT) resulted in
      more rapid declines in estimated glomerular filtration rates (eGFRs) than in the
      standard arm (SBP<140mmHg). Whether this change reflects hemodynamic effects or
      accelerated intrinsic kidney damage is unknown. STUDY DESIGN: Longitudinal
      subgroup analysis of clinical trial participants. SETTINGS & PARTICIPANTS: Random
      sample of SPRINT participants with prevalent chronic kidney disease (CKD) defined
      as eGFR<60mL/min/1.73m2 by the CKD-EPI (CKD Epidemiology Collaboration)
      creatinine-cystatin C equation at baseline. OUTCOMES & MEASUREMENTS: Urine
      biomarkers of tubule function (beta2-microglobulin [B2M], alpha1-microglobulin
      [A1M]), and uromodulin), injury (interleukin 18, kidney injury molecule 1, and
      neutrophil gelatinase-associated lipocalin), inflammation (monocyte
      chemoattractant protein 1), and repair (human cartilage glycoprotein 40) at
      baseline, year 1, and year 4. Biomarkers were indexed to urine creatinine
      concentration and changes between arms were evaluated using mixed-effects linear
      models and an intention-to-treat approach. RESULTS: 978 SPRINT participants (519
      in the intensive and 459 in the standard arm) with prevalent CKD were included.
      Mean age was 72+/-9 years and eGFR was 46.1+/-9.4mL/min/1.73m2 at baseline.
      Clinical characteristics, eGFR, urinary albumin-creatinine ratio, and all 8
      biomarker values were similar across arms at baseline. Compared to the standard
      arm, eGFR was lower by 2.9 and 3.3mL/min/1.73m2 in the intensive arm at year 1
      and year 4. None of the 8 tubule marker levels was higher in the intensive arm
      compared to the standard arm at year 1 or year 4. Two tubule function markers
      (B2M and A1M) were 29% (95% CI, 10%-43%) and 24% (95% CI, 10%-36%) lower at year
      1 in the intensive versus standard arm, respectively. LIMITATIONS: Exclusion of
      persons with diabetes, and few participants had advanced CKD. CONCLUSIONS: Among
      participants with CKD in SPRINT, random assignment to the intensive SBP arm did
      not increase any levels of 8 urine biomarkers of tubule cell damage despite loss
      of eGFR. These findings support the hypothesis that eGFR declines in the
      intensive arm of SPRINT predominantly reflect hemodynamic changes rather than
      intrinsic damage to kidney tubule cells.

PMID- 30291014
TI  - HARMONY or discord in cardiovascular outcome trials of GLP-1 receptor agonists?

PMID- 30291015
TI  - How to develop a bibliographic search strategy.

PMID- 30291016
TI  - Findings From a Randomized Trial of Weight Gain Prevention Among Overweight
      Puerto Rican Young Adults.
AB  - OBJECTIVE: Assess impact of multimodality weight gain prevention intervention.
      METHODS: Randomized clinical trial among 39 overweight young Puerto Rico college
      students using 10 weekly peer-support sessions promoting dietary, physical
      activity, and other lifestyle changes enhanced by stress-reduction and
      mindfulness approaches. Body mass index (BMI) and self-reported behaviors were
      measured at baseline and at 10 weeks and 6 months after baseline. RESULTS: At the
      completion of the intervention, BMIs in the experimental arm were 0.8 units lower
      than at baseline (z = -3.0; P = .008) and 1.2 lower at 6 months after baseline (z
      = -4.1; P < .001); BMIs in the control arm were 0.7 higher (z = 2.7; P = .02) at
      10 weeks and 0.8 higher at 6 months (z = 3.1; P = .005). Group * time interaction
      confirmed that BMI differed significantly over time between arms (chi2 = 26.9;
      degrees of freedom = 2; P < .001). Analysis of behavioral changes was mostly
      inconclusive although the experimental arm reported a considerable increase in
      walking at 10 weeks. Qualitative data suggested that yoga and mindfulness
      components were particularly useful for motivating participants to maintain
      healthier lifestyle patterns. CONCLUSIONS: Body mass index in the experimental
      arm decreased at the end of intervention and was maintained at 6 months' follow
      up.

PMID- 30291017
TI  - Adjusted Citation Rate, an Alternative Metric to Measure the Impact of General
      Radiology Journals.
AB  - RATIONALE AND OBJECTIVES: The journal impact factor (JIF) is often used to assess
      the prestige of scientific journals. Citations from original articles and reviews
      as well as citations from noncitable items contribute to the numerator in these
      calculations. However, since noncitable articles are not included in the
      denominator, the JIF may be skewed by the types of articles and not accurately
      reflect the prestige of the journal. The purpose of our study was to develop an
      alternative and complementary metric by which journals may be assessed. This
      "adjusted citation rate metric" is based on citations that originate only from
      citable items in the journal. MATERIAL AND METHODS: We tabulated the number of
      citations and citable items for original articles from the Web of Science Core
      Collection for 5 consecutive years (2010-2014) for 20 general radiology journals.
      The adjusted citation rates (CR) per original article and reviews were calculated
      using only citations that originated from citable items. RESULTS: The adjusted CR
      in 2015 was similar to the JIF in 14 of the 20 journals, higher in four journals,
      and lower in two journals. Using this system, Radiology, Investigative Radiology,
      and European Radiology remained first, second, and third respectively among
      journals published in the field of general radiology. To allow for equal
      distribution of original articles vs reviews among general radiology journals, we
      calculated the adjusted CR where the standard distribution of original articles
      is 50%. CONCLUSION: Adjusted citation rate is an objective index for assessing
      journal impact that can serve as an alternative and complementary metric with
      which to measure the journal impact.

PMID- 30291018
TI  - Comorbid hypertension and diabetes among U.S. women of reproductive age:
      Prevalence and disparities.
AB  - AIMS: Diabetes is associated with significant pregnancy complications, which can
      be further exacerbated by comorbid hypertension. Racial/ethnic differentials in
      the burden of comorbid hypertension and diabetes among women of reproductive age
      have not been described. METHODS: Using Wave IV of the nationally representative
      National Longitudinal Study of Adolescent to Adult Health (Add Health), we
      analyzed survey and biological data from 6576 non-pregnant women who were aged 24
      32 in 2007-2008. Hypertension and diabetes were identified by self-report of
      diagnosis and biological measurements taken during in-home interviews. We used
      logistic regression models to predict the presence of comorbid hypertension and
      diabetes and whether each was diagnosed. RESULTS: Over a third (36.0%) of women
      with diabetes had comorbid hypertension. Compared to non-Hispanic white women,
      more non-Hispanic black women had comorbid hypertension and diabetes (adjusted
      odds ratio (aOR) 5.93, 95% CI 3.84-9.16), and, if comorbid, were less likely to
      have a diabetes diagnosis (aOR 0.03, 95% CI 0.007-0.1) or hypertension diagnosis
      (aOR 0.22, 95% CI 0.08-0.65). CONCLUSION: Comorbid hypertension and diabetes are
      more common among non-Hispanic black women and less likely to be diagnosed,
      signaling disparities threatening maternal and child health among women with
      diabetes.

PMID- 30291019
TI  - Risk of Serious Bacterial Infection in Infants Aged <=60 Days Presenting to
      Emergency Departments with a History of Fever Only.
AB  - OBJECTIVE: To compare the risk of serious bacterial infection between infants
      aged <=60 days who are febrile in the emergency department (ED) and those who
      have only a history of fever and are afebrile on arrival to the ED. STUDY DESIGN:
      In this secondary analysis of a multicenter prospective study using data
      collected between December 2008 and May 2013, we compared the rate of serious
      bacterial infection (urinary tract infection [UTI], bacteremia, and/or bacterial
      meningitis) between infants who have a history of fever but are afebrile on
      arrival to the ED and those with fever documented in the ED (rectal temperature
      >=38.0  degrees C) using relative risk (RR) with 95% CI. Stratified analyses were
      performed for age (<=28 and 29-60 days) and serious bacterial infection type.
      Infants born prematurely and those with a clinical focal infection or serious
      illness were excluded. RESULTS: A total of 3825 infants (mean age, 35.2 days;
      56.9% male) were included. Of the 1233 (32.2%) who were afebrile in the ED, 108
      (8.8%) had a serious bacterial infection (UTI, n = 94 [7.6%]; bacteremia, n = 19
      [1.5%]; bacterial meningitis, n = 8 [0.6%]). Of the 2592 infants (67.8%) who were
      febrile in the ED, 331 (12.8%) had a serious bacterial infection (UTI, n = 285
      [11.0%]; bacteremia, n = 61 [2.4%]; bacterial meningitis, n = 17 [0.7%]). The RR
      for serious bacterial infection for afebrile vs febrile infants was 0.68 (95% CI,
      0.56-0.84). A lower risk of serious bacterial infection was also seen among
      afebrile vs febrile infants aged <=28 days (RR, 0.69; 95% CI, 0.52-0.93) and age
      29-60 days (RR, 0.67; 95% CI, 0.50-0.89). CONCLUSIONS: The prevalence of serious
      bacterial infection is lower in infants aged <=60 days with a history of fever
      compared with those who are febrile on arrival to the ED. The small risk
      reduction in this group is unlikely to alter decision making.

PMID- 30291020
TI  - Prognostic Factors and Management of Patients with Choanal Atresia.
AB  - OBJECTIVE: To analyze prognostic factors in the management of patients with
      choanal atresia. STUDY DESIGN: This is a review of 114 patients operated on for
      choanal atresia in a tertiary care center between November 1986 and November
      2016, including clinical characteristics, surgical management, and postoperative
      course with final nasal patency. The data were collected in a database that was
      updated over time. RESULTS: Among the 114 patients, 78 were female, 77 presented
      with unilateral choanal atresia, and 37 presented with bilateral unilateral
      choanal atresia, corresponding to 151 nasal fossae. Forty-seven patients had
      associated abnormalities (41.2%), including CHARGE, diagnosed in 20 children
      (17.5%). At the end of follow-up, 91 patients (79.8%) had normal choanal patency.
      The identified risk factors of surgical failure were age <6 months (P = .004),
      weight <5 kg (P = .007), and bilateral choanal atresia (P < .001). The type of
      atresia, presence of associated abnormalities, surgical approach, stenting, and
      use of mitomycin were not significantly linked with the surgical results.
      CONCLUSIONS: This series highlights the importance of the timing of surgery,
      which is guided by the clinical ability of the infant to tolerate the procedure.
      Endoscopic approaches are widely performed, but a transpalatal approach,
      necessary in some cases of bilateral choanal atresia, does not alter the results.
      Unilateral choanal atresia surgery should be delayed after age 6 months and/or
      weight >5 kg when possible.

PMID- 30291021
TI  - Parent Perspectives on Readiness for Discharge Home after Neonatal Intensive Care
      Unit Admission.
AB  - OBJECTIVE: To explore the parent perspective on discharge home from the neonatal
      intensive care unit (NICU). STUDY DESIGN: We interviewed parents of NICU
      graduates with a range of demographic characteristics and medical complexities to
      explore parent perspectives on readiness for discharge. Interviews were
      transcribed and coded by a 6-member team. We performed content analysis to
      identify themes and develop a family-centered conceptual framework around
      readiness for NICU discharge. RESULTS: We interviewed a total of 15 parents who
      experienced NICU stays with 18 infants. Parents who have experienced NICU
      discharge have a spectrum of needs that evolve from the time the child is in the
      NICU, at time of discharge, and at home afterward. These needs consistently
      centered around 5 themes-communication, parent role clarity, emotional support,
      knowledge sources, and financial resources. CONCLUSIONS: Parents described many
      ways the system could have better prepared them and connected them with essential
      resources. Summarizing the voices of the parents who participated in this study,
      we have compiled a series of practical recommendations for clinicians to use in
      daily practice to help parents feel prepared and confident for the transition
      home from the NICU.

PMID- 30291022
TI  - Long-Term Cardiovascular Morbidity in Children Born Following Fertility
      Treatment.
AB  - OBJECTIVE: To determine the risk of long-term cardiovascular disease (CVD) among
      children born following in vitro fertilization (IVF) and compared with
      spontaneous pregnancies. STUDY DESIGN: A population-based cohort study including
      all singleton deliveries occurring between 1991and 2014 at a tertiary medical
      center was performed. Hospitalizations up to the age of 18 years involving CVD
      were evaluated in children delivered following IVF, ovulation induction, and
      spontaneous pregnancies. CVD included valvular disorders, hypertension,
      arrhythmias, rheumatic disease, cardiomyopathy, ischemic heart disease, and heart
      failure. Kaplan-Meier survival curves were used to compare cumulative morbidity
      incidence, and a Cox regression model controlled for confounders. RESULTS: During
      the study period, 242 187 singleton deliveries met the inclusion criteria; 1.1%
      following IVF (n = 2603), and 0.7% following ovulation induction (n = 1721).
      Hospitalizations up to the age of 18 years involving CVD (n = 1503) were
      comparable in children delivered following IVF (0.6%), ovulation induction
      (0.7%), and spontaneous pregnancies (0.6%; P = .884). No significant difference
      in the cumulative incidence of CVD was noted between the groups (log rank P =
      .781). Controlling for maternal age, gestational age, birthweight, maternal
      diabetes, and hypertensive disorders in pregnancy, fertility treatment was not
      noted as a risk factor for long-term pediatric CVD (IVF adjusted hazard ratio
      1.05, 95% CI 0.63-1.74, P = .86; ovulation induction adjusted hazard ratio 0.97,
      CI 95% 0.55-1.71, P = .92). CONCLUSIONS: Singletons conceived via fertility
      treatments do not appear to be at an increased risk of long-term pediatric CVD.

PMID- 30291023
TI  - Predicting Successful Neonatal Retro-Transfer to a Lower Level of Care.
AB  - Up to 20% of newborn infants retro-transferred to a lower level of care require
      readmission to a higher-level facility. In this study, we developed and validated
      a prediction rule (The Rule for Elective Transfer between Units for Recovering
      Neonates [RETURN]) to identify clinical characteristics of infants at risk for
      failing retro-transfer.

PMID- 30291024
TI  - Prostaglandin E-major urinary metabolite as a noninvasive surrogate marker for
      infantile necrotizing enterocolitis.
AB  - BACKGROUND: Early definitive diagnosis of necrotizing enterocolitis (NEC) based
      on Bell's staging criteria is difficult because there are few observable changes
      on abdominal imaging and blood chemistry tests at the onset of the disease.
      PURPOSE: To investigate whether prostaglandin E-2 major urinary metabolite (PGE
      MUM) can be a useful surrogate marker reflecting the disease state and severity
      of NEC in infants. METHODS: Infants were enrolled in this study between January
      2014 and December 2016. NEC diagnosis was based on Bell's staging criteria >
      Stage II or necrotic bowel observed at surgery. After diagnosis, PGE-MUM level
      was measured and compared with that of the other disease and healthy infant
      groups. RESULTS: Median PGE-MUM value was highest in the NEC group (576 [65-3672]
      MUg/g*Cre/BSA * 1000), followed by the other disease group (94 [57-296]
      MUg/g*Cre/BSA * 1000) and the healthy infant group (19 [10-44] MUg/g*Cre/BSA *
      1000) (sensitivity: 92.3%, specificity: 81.5%, accuracy: 85.0%; p < 0.01). PGE
      MUM level correlated with improved status of NEC, length of necrotic intestine,
      and Bell's staging criteria. CONCLUSIONS: PGE-MUM level may be a useful surrogate
      biomarker reflecting the disease state of NEC. The method of urine sample
      collection is also advantageous, being noninvasive for infants. This is the first
      study reporting PGE-MUM level in NEC. TYPE OF STUDY: Study of diagnostic test.
      LEVEL OF EVIDENCE: LEVEL II.

PMID- 30291025
TI  - Distribution, diagnosis, and treatment of pulmonary sequestration: Report of 208
      cases.
AB  - OBJECTIVE: This study was performed to explore the clinical features, typing,
      distribution, and treatment of pulmonary sequestration (PS), with the aim of
      improving the awareness and treatment of this condition. METHODS: Clinical data
      regarding surgical procedures, outcomes, and prognosis of 208 pediatric patients
      with PS who were treated in our center from January 2005 to October 2017 were
      retrospectively analyzed. RESULTS: PS was confirmed by ultrasonography, enhanced
      computed tomography (CT), and/or magnetic resonance imaging (MRI) before surgery,
      and the surgeries were smoothly performed in all 208 patients (138 males, 70
      females; age, 1 month to 14 years; mean age, 19.70 +/- 48.82 months). The
      operative time ranged from 10 to 230 min (mean, 70 +/- 48.75 min), and the
      intraoperative blood loss volume ranged from 1 to 200 ml (mean, 5 +/- 18 ml). PS
      was located in multiple sites of the thoracic cavity and was also found in some
      rare locations such as the neck and abdomen. The feeding arteries of the PS
      mainly arose from the thoracic aorta or abdominal aorta, and a few of them
      originated from other vessels in the systemic circulation. The venous drainage
      differed between intralobar and extralobar PS: in patients with intralobar PS,
      the venous drainage was mainly via the pulmonary veins, especially the lower
      pulmonary veins; in patients with extralobar PS, the venous drainage was via the
      azygos vein and hemiazygos vein or reached the right atrium via the vena cava.
      The infection rate in children with intralobar sequestration was 71.17% (79/111),
      and that in children with extralobar sequestration was 31.37% (16/51).
      CONCLUSION: PS has increasingly been detected by prenatal ultrasonography, and
      enhanced CT and MRI are the main techniques for diagnosing PS. Once confirmed, PS
      should be surgically resected. We choose an age of 6 to 12 months for surgical
      resection. Minimally invasive video-assisted thoracic surgery has many advantages
      in the treatment of PS and can be the treatment of choice for this condition.
      TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: Level III.

PMID- 30291026
TI  - Complications after proctocolectomy and ileal pouch-anal anastomosis in pediatric
      patients: A systematic review.
AB  - BACKGROUND/PURPOSE: Colectomy with ileal pouch-anal anastomosis (IPAA) is the
      standard of care for patients with familial adenomatous polyposis (FAP) and
      refractory ulcerative colitis (UC). The rates of postoperative complications are
      not well established in children. The objective of this systematic review is to
      establish benchmark data for morbidity after pediatric IPAA. METHODS: PubMed,
      Embase, and The Cochrane Library were searched for studies of colectomy with IPAA
      in patients <=21 years old. UC studies were limited to the anti-tumor necrosis
      factor-alpha agents era (1998-present). All postoperative complications were
      extracted. RESULTS: Thirteen studies met the inclusion criteria (763 patients).
      Compared to patients with FAP, UC patients had a higher prevalence of pouch loss
      (10.6% vs. 1.5%). Other major complications such as anastomotic leak, abscess,
      and fistula were uncommon (mean prevalence 4.9%, 4.2%, and 5.0%, respectively,
      for patients with UC; 8.7%, 4.2%, and 4.3% for FAP). The most frequent
      complication was pouchitis (36.4% of UC patients). CONCLUSIONS: Devastating
      complications from colectomy and IPAA are rare, but patients with UC have poorer
      outcomes than those with FAP. Much of the morbidity may therefore stem from
      patient or disease factors. Multicenter, prospective studies are needed to
      identify modifiable risks in patients with UC undergoing IPAA. LEVEL OF EVIDENCE:
      Prognostic, level II.

PMID- 30291027
TI  - B Cells Are the Dominant Antigen-Presenting Cells that Activate Naive CD4+ T
      Cells upon Immunization with a Virus-Derived Nanoparticle Antigen.
AB  - B cells can present antigens to CD4+ T cells, but it is thought that dendritic
      cells (DCs) are the primary initiators of naive CD4+ T cell responses.
      Nanoparticles, including virus-like particles (VLPs), are attractive candidates
      as carriers for vaccines and drug delivery. Using RNA phage Qbeta-derived VLP
      (Qbeta-VLP) as a model antigen, we found that antigen-specific B cells were the
      dominant antigen-presenting cells that initiated naive CD4+ T cell activation. B
      cells were sufficient to induce T follicular helper cell development in the
      absence of DCs. Qbeta-specific B cells promoted CD4+ T cell proliferation and
      differentiation via cognate interactions and through Toll-like receptor signaling
      mediated cytokine production. Antigen-specific B cells were also involved in
      initiating CD4+ T cell responses during immunization with inactivated influenza
      virus. These findings have implications for the rational design of nanoparticles
      as vaccine candidates, particularly for therapeutic vaccines that aim to break
      immune tolerance.

PMID- 30291028
TI  - Secreted IgD Amplifies Humoral T Helper 2 Cell Responses by Binding Basophils via
      Galectin-9 and CD44.
AB  - B cells thwart antigenic aggressions by releasing immunoglobulin M (IgM), IgG,
      IgA, and IgE, which deploy well-understood effector functions. In contrast, the
      role of secreted IgD remains mysterious. We found that some B cells generated IgD
      secreting plasma cells following early exposure to external soluble antigens such
      as food proteins. Secreted IgD targeted basophils by interacting with the CD44
      binding protein galectin-9. When engaged by antigen, basophil-bound IgD increased
      basophil secretion of interleukin-4 (IL-4), IL-5, and IL-13, which facilitated
      the generation of T follicular helper type 2 cells expressing IL-4. These
      germinal center T cells enhanced IgG1 and IgE but not IgG2a and IgG2b responses
      to the antigen initially recognized by basophil-bound IgD. In addition, IgD
      ligation by antigen attenuated allergic basophil degranulation induced by IgE co
      ligation. Thus, IgD may link B cells with basophils to optimize humoral T helper
      type 2-mediated immunity against common environmental soluble antigens.

PMID- 30291030
TI  - Clinical Outcomes of Valvular versus Nonvalvular Atrial Fibrillation in Acute
      Anterior Circulation Occlusive Stroke Undergoing Endovascular Treatment.
AB  - BACKGROUND: Thrombectomy is the first choice for cardioembolism due to atrial
      fibrillation (AF), however, whether valvular AF and nonvalvular AF had different
      safety and functional outcomes has not been reported yet. We aimed to investigate
      the differences between patients with valvular AF and patients with nonvalvular
      AF on safety and functional outcomes in acute large artery occlusion undergoing
      thrombectomy. METHODS: Valvular AF refers to patients with mitral stenosis or
      artificial heart valves and valve repair. Rate of symptomatic intracerebral
      hemorrhage [sICH], modified Rankin Scale Score (mRS), and death at 90days were
      compared between valvular AF and nonvalvular AF groups. Univariate and
      multivariable logistic regression was performed to identify the predictors for
      unfavorable functional outcome (mRS 3-6). RESULTS: 18.8% (51/271) of AF were
      valvular AF. The valvular AF group had significantly higher proportion of mRS 0-2
      (49% [25/51] versus 33.3% [73/219], P = .04) and less death (21.6% [11/51] versus
      38.4% [84/219], P = .02) comparing with nonvalvular AF group. The rates of sICH
      between both groups were nonsignificantly different (21.5% [47/219] for
      nonvalvular AF versus 13.7% [7/51] for valvular AF, P = .46). Valvular AF was not
      an independent predictor for unfavorable functional outcome (odds ratio .67, 95%
      confidence interval: .24-1.84) with age, collateral flow, chronic heart failure,
      NIHSS at admission, recanalization status, glucose at admission, occlusion site,
      ASPECTS, and ICH as covariates. CONCLUSIONS: Valvular AF and nonvalvular AF have
      similar safety andfunctional outcomes in patients with acute anterior circulation
      large artery occlusion undergoing thrombectomy.

PMID- 30291029
TI  - Regulatory T Cells Promote Macrophage Efferocytosis during Inflammation
      Resolution.
AB  - Regulatory T (Treg) cell responses and apoptotic cell clearance (efferocytosis)
      represent critical arms of the inflammation resolution response. We sought to
      determine whether these processes might be linked through Treg-cell-mediated
      enhancement of efferocytosis. In zymosan-induced peritonitis and
      lipopolysaccharide-induced lung injury, Treg cells increased early in resolution,
      and Treg cell depletion decreased efferocytosis. In advanced atherosclerosis,
      where defective efferocytosis drives disease progression, Treg cell expansion
      improved efferocytosis. Mechanistic studies revealed the following sequence: (1)
      Treg cells secreted interleukin-13 (IL-13), which stimulated IL-10 production in
      macrophages; (2) autocrine-paracrine signaling by IL-10 induced Vav1 in
      macrophages; and (3) Vav1 activated Rac1 to promote apoptotic cell engulfment. In
      summary, Treg cells promote macrophage efferocytosis during inflammation
      resolution via a transcellular signaling pathway that enhances apoptotic cell
      internalization. These findings suggest an expanded role of Treg cells in
      inflammation resolution and provide a mechanistic basis for Treg-cell-enhancement
      strategies for non-resolving inflammatory diseases.

PMID- 30291013
TI  - Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and
      cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo
      controlled trial.
AB  - BACKGROUND: Glucagon-like peptide 1 receptor agonists differ in chemical
      structure, duration of action, and in their effects on clinical outcomes. The
      cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown.
      We aimed to determine the safety and efficacy of albiglutide in preventing
      cardiovascular death, myocardial infarction, or stroke. METHODS: We did a double
      blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We
      randomly assigned patients aged 40 years and older with type 2 diabetes and
      cardiovascular disease (at a 1:1 ratio) to groups that either received a
      subcutaneous injection of albiglutide (30-50 mg, based on glycaemic response and
      tolerability) or of a matched volume of placebo once a week, in addition to their
      standard care. Investigators used an interactive voice or web response system to
      obtain treatment assignment, and patients and all study investigators were masked
      to their treatment allocation. We hypothesised that albiglutide would be non
      inferior to placebo for the primary outcome of the first occurrence of
      cardiovascular death, myocardial infarction, or stroke, which was assessed in the
      intention-to-treat population. If non-inferiority was confirmed by an upper limit
      of the 95% CI for a hazard ratio of less than 1.30, closed testing for
      superiority was prespecified. This study is registered with ClinicalTrials.gov,
      number NCT02465515. FINDINGS: Patients were screened between July 1, 2015, and
      Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled
      and randomly assigned to groups: 4731 patients were assigned to receive
      albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was
      determined that 611 primary endpoints and a median follow-up of at least 1.5
      years had accrued, and participants returned for a final visit and
      discontinuation from study treatment; the last patient visit was on March 12,
      2018. These 9463 patients, the intention-to-treat population, were evaluated for
      a median duration of 1.6 years and were assessed for the primary outcome. The
      primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence
      rate of 4.6 events per 100 person-years in the albiglutide group and in 428 (9%)
      of 4732 patients at an incidence rate of 5.9 events per 100 person-years in the
      placebo group (hazard ratio 0.78, 95% CI 0.68-0.90), which indicated that
      albiglutide was superior to placebo (p<0.0001 for non-inferiority; p=0.0006 for
      superiority). The incidence of acute pancreatitis (ten patients in the
      albiglutide group and seven patients in the placebo group), pancreatic cancer
      (six patients in the albiglutide group and five patients in the placebo group),
      medullary thyroid carcinoma (zero patients in both groups), and other serious
      adverse events did not differ between the two groups. There were three (<1%)
      deaths in the placebo group that were assessed by investigators, who were masked
      to study drug assignment, to be treatment-related and two (<1%) deaths in the
      albiglutide group. INTERPRETATION: In patients with type 2 diabetes and
      cardiovascular disease, albiglutide was superior to placebo with respect to major
      adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor
      agonists should therefore be considered as part of a comprehensive strategy to
      reduce the risk of cardiovascular events in patients with type 2 diabetes.
      FUNDING: GlaxoSmithKline.

PMID- 30291031
TI  - Does the Magnitude of the Electrocardiogram QT Interval Dispersion Predict Stroke
      Outcome?
AB  - BACKGROUND: QT dispersion, maximal interlead difference in QT interval on 12-lead
      electrocardiogram (ECG), measures cardiac repolarization abnormalities. Data are
      conflicting whether QT dispersion predicts adverse outcome in acute ischemic
      stroke (AIS) patients. Our objective is to determine if QT dispersion predicts:
      (1) short-term clinical outcome in AIS, and (2) stroke location (insular versus
      noninsular cortex). METHODS: Admission ECGs from 412 consecutive patients with
      acute stroke symptoms from 2 university-based stroke centers were reviewed. QT
      dispersion was measured. A neuroradiologist reviewed brain imaging for insular
      cortex involvement. Favorable clinical outcomes at discharge were modified Rankin
      Scale (mRS) score of 0-1, discharge National Institutes of Health Stroke Scale
      (NIHSS) score less than 2, and discharge to home. Multiple logistic regressions
      were performed for each outcome measure and to determine the association between
      insular infarct and QT dispersion. RESULTS: Of 145 subjects in the final
      analysis, median age was 65years (interquartile range [IQR] 56-75), male patients
      were 38%, black patients were 68%, median QT dispersion was 78 milliseconds (IQR
      59-98), and median admission NIHSS score was 4 (IQR 2-6). QT dispersion did not
      predict short-term clinical outcome for mRS score (odds ratio [OR] = 1.001, 95%
      confidence interval [CI] .99-1.01, P = .85), NIHSS at discharge (OR = .994, 95%
      CI .98-1.01, P = .30), or discharge disposition (OR = 1.001, 95% CI .99-1.01, P =
      .81). Insular cortex involvement did not correlate with QT dispersion magnitude
      (OR = 1.009, 95% CI .99-1.02, P = .45). CONCLUSIONS: We could not demonstrate
      that QT dispersion is useful in predicting short-term clinical outcome at
      discharge in AIS. Further, the magnitude of QT dispersion did not predict insular
      cortical stroke location.

PMID- 30291032
TI  - Ten-year epidemiological study in an orthopaedic and trauma surgery centre: Are
      there risks involved in increasing scheduled arthroplasty volume without
      increasing resources?
AB  - BACKGROUND: Current trends in patient management include decreasing hospital stay
      lengths and reductions in available material and human resources. A shortening of
      hospital stays in university hospitals has been documented over the last decade.
      However, to our knowledge, no study has assessed possible relationships linking
      shorter stays to staffing levels or complication rates. The objectives of this
      study were: 1) to assess changes in case volume in a university orthopaedics and
      trauma surgery department between 2006 and 2016, 2) and to look for correlations
      linking these changes to staffing levels and the rates of significant
      complications, including the number of hip dislocations after total hip
      arthroplasty (THA) and the number of infections and complications resulting in
      malpractice litigation after hip, knee, or shoulder arthroplasty. HYPOTHESIS: The
      case volume increased during the study period, whereas resources remained
      unchanged or decreased. MATERIAL AND METHODS: A retrospective study was performed
      using the electronic database of an orthopaedics and trauma surgery department.
      Data collected between 2006 and 2016 were analysed. Mean hospital stay length,
      patient age, and surgical volume were recorded, and changes over time in case
      volume for trauma surgery and scheduled arthroplasties were evaluated. Changes in
      staffing levels and rates of complications (dislocation after THA and infections
      and complications resulting in malpractice litigation) between 2006 and 2016 were
      assessed. Only arthroplasty procedures performed in the department were
      considered for the study of complications and litigation. RESULTS: Between 2006
      and 2016, mean hospital stay decreased from 8.7+/-10.8 days (range, 0-141 days)
      in to 7.0+/-9.4 days (range, 0-150 days). Mean patient age increased from 54.4+/
      21.2 years (range, 11.7-100.9 years) in 2006 to 59.3+/-20.9 years (range, 13.2
      103.1 years) in 2016. The total number of procedures rose from 2158 in 2006 to
      3100 in 2016 (+43.6%). The number of THAs increased by 16.2% and the number of
      total knee arthroplasties by 96.7%. The number of operations for trauma increased
      from 725 in 2006 to 1135 in 2016 (+56.0%). During the study period, the number of
      hospital beds declined from 70 to 55. No increase was seen in the frequencies of
      dislocation after THA (3/284 [1.4%] in 2006 and 4/330 [1.2%] in 2016) or
      prosthetic joint infection (5/439 [1.1%] in 2006 and 6/657 [0.9%] in 2016). In
      contrast, malpractice suits filed by patients after arthroplasty increased from
      1/439 (0.2%) in 2006 to 8/657 (1.2%) in 2016. CONCLUSION: Over the last decade,
      trauma and arthroplasty surgical volumes increased substantially, whereas
      staffing levels remained unchanged and number of beds diminished. The frequency
      of significant complications such as dislocation after THA did not increase. In
      contrast, a marked rise was seen in malpractice litigation. However, the
      increased volume with unchanged resources found in this study should be
      interpreted in the light of the marked increase in patient dependency and of our
      role as a referral centre managing patients with complications after surgery
      performed at other institutions. LEVEL OF EVIDENCE: IV, retrospective
      observational study.

PMID- 30291033
TI  - Aggressive imaging in young children on antithrombotic therapy with minor
      traumatic head injury.

PMID- 30291034
TI  - Lemierre's syndrome: A forgotten complication of acute pharyngitis.

PMID- 30291035
TI  - Investigation of age-adjusted D-dimer using an uncommon assay.
AB  - BACKGROUND: Use of an age-adjusted D-dimer for the evaluation of acute pulmonary
      embolus (PE) has been prospectively validated in the literature and has become a
      practice recommendation from major medical societies. Most research on this
      subject involves the most common D-dimer assays reporting in Fibrinogen
      Equivalent Units (FEU) with a non-age-adjusted manufacturer-recommended cutoff of
      500 ng/ml FEU. Limited research to date has evaluated age-adjustment in assays
      that report in D-Dimer Units (D-DU), which use a manufacturer-recommended cutoff
      of 230 ng/ml D-DU. Despite scant evidence, an age-adjusted formula using D-DU has
      been recently endorsed by the American College of Emergency Physicians (ACEP).
      This formula seems arbitrary in its derivation and unnecessarily deviates from
      existing thresholds, thus prompting the creation of our novel-age adjustment
      formula. The goal of this study was to retrospectively evaluate the test
      characteristics of our novel age-adjusted D-dimer formula using the D-DU assay in
      comparison to existing traditional and age-adjusted D-dimer thresholds for the
      evaluation of acute PE in the ED. METHODS: This was a retrospective chart review
      at an academic quaternary health system with three EDs and 195,000 combined
      annual ED visits. Only patients with D-dimer testing and CT PE protocol (CTPE)
      imaging were included. Admission and discharge diagnosis codes were used to
      identify acute PE. Outcome measures were sensitivity, specificity, negative
      predictive value (NPV) and positive predictive value (PPV) of an unadjusted
      traditional threshold (230) compared with both novel and ACEP-endorsed age
      adjusted thresholds, (Age * 5) - 20 and Age * 5 if >50, respectively. Estimates
      with their exact 95% threshold were performed. RESULTS: 4846 adult patients were
      evaluated from January 2012 to July 2017. Group characteristics include a mean
      age of 52 and a frequency of acute PE diagnosis by CTPE of 8.25%. Traditional D
      dimer cutoff demonstrated a sensitivity of 99.8% (95% CI 98.6-100), specificity
      of 16.7% (95% CI 15.6-17.8) and NPV of 99.9% (95% CI 99.3-100). Our novel age
      adjusted D-dimer thresholds had a sensitivity of 97.0% (95% CI 94.8-98.4),
      specificity of 27.9% (95% CI 26.6-29.2) and NPV of 99.0% (95% CI 98.3-99.5) with
      the ACEP-endorsed formula demonstrating similar test characteristics. CONCLUSION:
      Use of an age-adjusted D-dimer on appropriately selected patients being evaluated
      for acute PE in the ED with a D-DU assay increases specificity while maintaining
      a high sensitivity and NPV. Both our novel formula and the ACEP-endorsed age
      adjusted formula performed well, with our novel formula showing a trend towards
      improved testing characteristics.

PMID- 30291036
TI  - Intestinal pseudo-obstruction as the initial manifestation of systemic lupus
      erythematosus.
AB  - Small bowel obstruction is common in emergency departments. However, the exact
      cause of intestinal pseudo-obstruction (IPO) is often misdiagnosed. IPO is
      considered a severe manifestation of systemic lupus erythematosus (SLE). However,
      IPO is rare as the initial manifestation of SLE. This paper reports a female
      patient who presented with IPO as the initial manifestation and was ultimately
      diagnosed with SLE. The 31-year-old female was definitively diagnosed with SLE
      after IPO symptoms for 1 month. She then presented multiple organ dysfunction
      syndrome (MODS) leading to a poor prognosis. Patients with unexplained SBO
      symptoms should be aware of systemic diseases. Early diagnosis and prompt medical
      treatment are crucial to avoid unnecessary surgery and obtain satisfactory
      outcomes.

PMID- 30291037
TI  - The SDQ dysregulation profile is associated with self-injurious thoughts and
      behaviors in adolescents evaluated at a clinical setting.
AB  - INTRODUCTION: Suicidal ideation, suicidal behavior, and non-suicidal self-injury
      behavior are serious public health problems among adolescents. A significant
      proportion of adolescents evaluated in clinical settings meet criteria for the
      dysregulation profile (DP). DP is characterized by restlessness, irritability,
      "affective storms", mood instability, and aggression in a disproportionate grade
      to the situation. This DP might be related to increased risk of self-injurious
      thoughts and behaviors. METHODS: Two hundred and thirty-nine adolescents from the
      Child and Adolescent Outpatient Psychiatric Services of the Jimenez Diaz
      Foundation, Madrid, were assessed with the Strengths and Difficulties
      Questionnaire-Dysregulation Profile, the Self-Injurious Thoughts and Behaviors
      Interview and socio-demographic questionnaires. RESULTS: Logistic regression
      showed that DP adolescents were at increased risk for suicide plans, gestures,
      and suicide attempts. They also tended to present more self-injurious behaviors
      than adolescents without DP. CONCLUSIONS: Our results point to the role of self
      regulatory problems in the presence of suicide plans, suicide gestures, suicide
      attempts, and in non-suicidal self-injury behavior. Longitudinal studies are
      needed to confirm the relationship between the Strengths and Difficulties
      Questionnaire-Dysregulation Profile and self-injurious thoughts and behaviors.

PMID- 30291038
TI  - Dental health in advanced age and Alzheimer's Disease: A possible link with
      bacterial toxins entering the brain?
AB  - We investigated a possible link between bacterial infestation of the oral cavity,
      dental health and Alzheimer's dementia (AD). Resistant germs on the surface of
      the maxillary molars are the cause of a complex biofilm of bacteria with the
      effect of a colonization of germs between oral cavity and maxillary sinus.
      Bacterial toxins may lead to subsequent inflammatory processes transgressing to
      neighboring central nervous system structures that are suspected to be crucial in
      the inception of AD, such as the entorhinal cortex and the hippocampus.

PMID- 30291039
TI  - Modelling cervical cancer elimination.

PMID- 30291040
TI  - The projected timeframe until cervical cancer elimination in Australia: a
      modelling study.
AB  - BACKGROUND: In 2007, Australia was one of the first countries to introduce a
      national human papillomavirus (HPV) vaccination programme, and it has since
      achieved high vaccination coverage across both sexes. In December, 2017,
      organised cervical screening in Australia transitioned from cytology-based
      screening every 2 years for women aged from 18-20 years to 69 years, to primary
      HPV testing every 5 years for women aged 25-69 years and exit testing for women
      aged 70-74 years. We aimed to identify the earliest years in which the annual age
      standardised incidence of cervical cancer in Australia (which is currently seven
      cases per 100 000 women) could decrease below two annual thresholds that could be
      considered to be potential elimination thresholds: a rare cancer threshold (six
      new cases per 100 000 women) or a lower threshold (four new cases per 100 000
      women), since Australia is likely to be one of the first countries to reach these
      benchmarks. METHODS: In this modelling study, we used Policy1-Cervix-an
      extensively validated dynamic model of HPV vaccination, natural history, and
      cervical screening-to estimate the age-standardised incidence of cervical cancer
      in Australia from 2015 to 2100. We incorporated age-specific coverage of the
      Australian National HPV Vaccination Program in girls, including the catch-up
      programme, and the inclusion of boys into the vaccine programme from 2013, and a
      change from the quadrivalent to the nonavalent vaccine from 2018. We also
      modelled the effects of the transition to primary HPV screening. We considered
      two scenarios for future screening recommendations regarding the cohorts who will
      be and who have been offered the nonavalent vaccine: either that HPV screening
      every 5 years continues, or that no screening would be offered to these women.
      FINDINGS: We estimate that, in Australia, the age-standardised annual incidence
      of cervical cancer will decrease to fewer than six new cases per 100 000 women by
      2020 (range 2018-22), and to fewer than four new cases per 100 000 women by 2028
      (2021-35). The precise year of attaining these rates is dependent on the
      population used for age-standardisation, HPV screening behaviour and test
      characteristics, the incremental effects of vaccination of men on herd immunity
      in women, and assumptions about the future frequency of benign hysterectomies. By
      2066 (2054-77), the annual incidence of cervical cancer will decrease and remain
      at fewer than one case per 100 000 women if screening for HPV every 5 years
      continues for cohorts who have been offered the nonavalent vaccine, or fewer than
      three cases per 100 000 women if these cohorts are not screened. Cervical cancer
      mortality is estimated to decrease to less than an age-standardised annual rate
      of one death per 100 000 women by 2034 (2025-47), even if future screening is
      only offered to older cohorts that were not offered the nonavalent vaccine.
      INTERPRETATION: If high-coverage vaccination and screening is maintained, at an
      elimination threshold of four new cases per 100 000 women annually, cervical
      cancer could be considered to be eliminated as a public health problem in
      Australia within the next 20 years. However, screening and vaccination
      initiatives would need to be maintained thereafter to maintain very low cervical
      cancer incidence and mortality rates. FUNDING: National Health and Medical
      Research Council (Australia).

PMID- 30291041
TI  - 131I uptake in tumoral calcinosis in a patient on hemodialysis treated for
      thyroid cancer.

PMID- 30291042
TI  - Bactericidal activity of ceftobiprole combined with different antibiotics against
      selected Gram-positive isolates.
AB  - This study investigated the in vitro susceptibility of ceftobiprole and its
      potential synergistic activity in combination with other antimicrobials against
      46 selected Gram-positive pathogens displaying resistance or decrease
      susceptibility to several drugs. The gradient-cross method was used to assess
      synergism between ceftobiprole and daptomycin, levofloxacin, linezolid,
      rifampicin and piperacillin/tazobactam. Time-kill curves were performed for seven
      representative isolates. Ceftobiprole MICs ranged from 0.25-6 mg/L for
      staphylococci; 4->=32 mg/L for Enterococcus faecalis, and 0.38->=32 mg/L for E.
      faecium. Ceftobiprole plus daptomycin was synergistic against all isolates.
      Ceftobiprole plus linezolid was synergistic against 4 isolates belonging to
      different species. Ceftobiprole plus levofloxacin was synergistic only against
      enterococci. In conclusion, ceftobiprole exhibited a potent in vitro
      antibacterial activity and exhibited synergy with daptomycin against all Gram
      positive isolates, despite their antibiotic resistance phenotypes. The use of
      ceftobiprole in combination may provide a promising alternative therapy for the
      treatment of resistant Gram-positive infections.

PMID- 30291043
TI  - Are there safe VITEK2 MIC cutoffs to avoid errors in colistin susceptibility
      testing?

PMID- 30291044
TI  - Replication protein A as a modulator of the poly(ADP-ribose)polymerase 1
      activity.
AB  - Replication protein A contributes to all major pathways of DNA metabolism and is
      a target for post-translation modifications, including poly(ADP-ribosyl)ation
      catalyzed by PARP1. Here we demonstrate that the efficiency of RPA poly(ADP
      ribosyl)ation strongly depends on the structure of DNA used for PARP1 activation
      and on the polarity of RPA binding. Moreover, RPA influences PARP1 activity, and
      this effect also depends on DNA structure: RPA inhibits PAR synthesis catalyzed
      by PARP1 in the presence of ssDNA and stimulates it in the presence of a DNA
      duplex, in particular that containing a nick or a gap. Using fluorescently
      labeled proteins, we showed their direct interaction and characterized it
      quantitatively. RPA can accelerate the replacement of poly(ADP-ribosyl)ated PARP1
      molecules bound to DNA by the unmodified ones. Thus, our data allow us to suggest
      that the balance between the affinities of PARP1 and RPA for DNA and the
      interaction of these proteins with each other are the cornerstone of the
      modulating effect of RPA on PARP1 activity. This effect might contribute to the
      regulation of PARP1 activity in various DNA processing mechanisms including DNA
      replication and repair pathways, where both PARP1 and RPA participate.

PMID- 30291045
TI  - The rising incidence and impact of non-medically indicated pre-labour cesarean
      section in Latin America.
AB  - In the poorest populations of the world the difficulties of performing a surgical
      procedure lead to extremely low cesarean section rates associated with very high
      perinatal mortality. Meanwhile the proportion of births by cesarean section has
      been increasing for several decades in many areas of the world, reaching
      alarmingly high rates especially in Latin America. This review aims to describe
      this secular trend. The causes of the increase in cesarean deliveries are
      analyzed with a multidimensional approach, trying to recognize the reasons behind
      the choice of the route of delivery. We are facing a shift in the guiding
      paradigm, leaving the classical biomedical one. Advantages and disadvantages of
      non-medically indicated cesarean section are being sought, comparing it with the
      results of vaginal delivery, with special emphasis on the short- and long-term
      morbidity of the newborn. Several variables involved in this controversial topic
      are considered, with the objective of stimulating critical thoughts about the
      medical, bioethical and social aspects of the increasing trend in the cesarean
      section rate.

PMID- 30291046
TI  - The meshed biological matrix in immediate, definitive breast reconstruction.

PMID- 30291047
TI  - Use of a perforator/subcutaneous pedicled propeller flap for reconstruction of
      lower eyelid defects.
AB  - Full-thickness skin grafts (FTSGs) and flaps from the upper eyelid or cheek can
      be used for reconstruction of lower eyelid defects, including the anterior
      lamella. However, the upper eyelid has a limited and insufficient amount of skin,
      whereas cheek flaps have a restricted arch of rotation. Here we report the
      procedure and outcomes of a perforator/subcutaneous pedicled propeller flap for
      reconstruction of lower eyelid defects including the anterior lamella. A
      retrospective study of 12 patients who underwent treatment for eyelid anterior
      lamella defects with perforator/subcutaneous pedicled propeller flaps was
      conducted between March 2015 and June 2017. The propeller flap was planned to
      rotate around the perforator (as the pivot point), which was detected with a hand
      held Doppler in the vicinity of the defect. The flaps were perforator pedicled
      for 10 patients and subcutaneous pedicled for the other two patients. The flap
      was rotated around the pedicle and placed on each patient's defect without
      tension. No vascular compromise occurred with any of the flaps. The most
      important complications were post-operative oedema and ecchymosis. Inferior
      eyelid defects including the anterior lamella could be reconstructed by using
      propeller flaps from the adjacent tissue. The main advantages of this flap
      included easy access to the defect, no impairment in eyelid function and very
      good aesthetic results.

PMID- 30291048
TI  - Septocutaneous thoracodorsal artery perforator flaps: a retrospective cohort
      study.
AB  - BACKGROUND: This study aimed to investigate the versatility of septocutaneous
      thoracodorsal artery perforator (TDAP-sc) flaps in various areas in the body and
      the running pattern of septocutaneous perforators. METHODS: This retrospective
      cohort study included 20 consecutive patients who underwent reconstruction of an
      oncological defect with a TDAP-sc flap from May 2014 to January 2018. Fifteen
      flaps were free, and the remaining five were pedicled. Surgical details and
      postoperative complications were investigated. RESULTS: The flap size ranged from
      13 * 6.5 to 22 * 15 cm. The defect location was the upper extremity in eight
      patients, the head and neck in six, the lower extremity in four, and the trunk in
      two. The septocutaneous perforator arose from the thoracodorsal vessels proximal
      to the serratus anterior branch in 10 (50.0%) patients, from the thoracodorsal
      vessels distal to the serratus anterior branch in six (30.0%), and from the
      serratus anterior branch in four (20.0%). All flaps completely survived, except
      the one with partial necrosis. The scapula was simultaneously harvested based on
      the angular branch in three patients who underwent mandibular reconstruction.
      CONCLUSIONS: The TDAP-sc flap can be a versatile option for various types of
      reconstruction if a dominant septocutaneous perforator is present. Prevalence of
      a dominant TDAP-sc is estimated at approximately 50%. However, this flap can be
      harvested without tedious intramuscular dissection, and the two-team approach is
      possible during tumor resection. The presence of a dominant septocutaneous
      perforator can expand indication of the TDAP flap.

PMID- 30291049
TI  - Anatomic location of a sensory nerve to the transverse upper gracilis (TUG) flap:
      A novel option for sensate autologous tissue reconstruction.

PMID- 30291050
TI  - Predictors of complications following breast reduction surgery: A National
      Surgical Quality Improvement Program study of 16,812 cases.
AB  - BACKGROUND: Breast reduction is one of the most common procedures performed by
      plastic surgeons. Despite good outcomes and high patient satisfaction, there are
      little national data on the predictors that lead to complications in this patient
      population. We accessed a national outcomes database to examine these factors.
      METHODS: This is a retrospective study examining the National Surgical Quality
      Improvement Program database from 2006 to 2015. Patients who underwent primary
      breast reduction were identified. Patients who underwent any cancer-related
      procedures were excluded. We identified patient-related and procedure-related
      factors for analysis. Univariate and multivariate logistic regression analyses
      were used to identify independent predictors of complications. RESULTS: In total,
      16,812 individual cases were identified. The overall complication rate for the
      cohort was 6.2%, and the major complication rate was 3.0%. Diabetes, bleeding
      disorder, hypertension, obesity, smoking, steroid use, and prolonged operative
      time were associated with increased risk of complications (p < 0.05). Concurrent
      body contouring was a predictor of increased major complications; however,
      liposuction was not. CONCLUSIONS: Common surgical risk factors are associated
      with complications in breast reduction surgery. Although liposuction is not an
      independent risk factor, concurrent body contouring is associated with increased
      complications. Surgeons should be aware of these associations when discussing
      breast reduction with patients.

PMID- 30291051
TI  - Smartphone App Use for Diabetes Management: Evaluating Patient Perspectives.
AB  - BACKGROUND: Finding novel ways to engage patients in chronic disease management
      has led to increased interest in the potential of mobile health technologies for
      the management of diabetes. There is currently a wealth of smartphone apps for
      diabetes management that are available for free download or purchase. However,
      the usability and desirability of these apps has not been extensively studied.
      These are important considerations, as these apps must be accepted by the patient
      population at a practical level if they are to be utilized. OBJECTIVE: The
      purpose of this study was to gain insight into patient experiences related to the
      use of smartphone apps for the management of type 1 diabetes. METHODS: Adults
      with type 1 diabetes who had previously (or currently) used apps to manage their
      diabetes were eligible to participate. Participants (n=12) completed a
      questionnaire in which they were required to list the names of preferred apps and
      indicate which app functions they had used. Participants were given the
      opportunity to comment on app functions that they perceived to be missing from
      the current technology. Participants were also asked whether they had previously
      paid for an app and whether they would be willing to do so. RESULTS: MyFitnessPal
      and iBGStar were the apps most commonly listed as the best available on the
      market. Blood glucose tracking, carbohydrate counting, and activity tracking were
      the most commonly used features. Ten participants fulfilled all eligibility
      criteria, and indicated that they had not encountered any one app that included
      all of the functions that they had used. The ability to synchronize an app with a
      glucometer or insulin pump was the most common function that participants stated
      was missing from current app technology. One participant had previously paid for
      a diabetes-related app and the other 9 participants indicated that they would be
      willing to pay. CONCLUSIONS: Despite dissatisfaction with the currently available
      apps, there is interest in using these tools for diabetes management. Adapting
      existing technology to better meet the needs of this patient population may allow
      these apps to become more widely utilized.

PMID- 30291052
TI  - Mixed-Methods Research in Diabetes Management via Mobile Health Technologies: A
      Scoping Review.
AB  - BACKGROUND: Considering the increasing incidence and prevalence of diabetes
      worldwide and the high level of patient involvement it requires, diabetes self
      management is a serious issue. The use of mobile health (mHealth) in diabetes
      self-management has increased, but so far research has not provided sufficient
      information about the uses and effectiveness of mHealth-based interventions.
      Alternative study designs and more rigorous methodologies are needed. Mixed
      methods designs may be particularly useful because both diabetes self-management
      and mHealth studies require integrating theoretical and methodological
      approaches. OBJECTIVE: This scoping review aimed to examine the extent of the use
      of mixed-methods research in mHealth-based diabetes management studies. The
      methodological approaches used to conduct mixed-methods studies were analyzed,
      and implications for future research are provided. METHODS: Guided by Arksey and
      O'Malley's framework, this scoping review implemented a comprehensive search
      strategy including reviewing electronic databases, key journal searches, Web
      based research and knowledge centers, websites, and handsearching reference lists
      of the studies. The studies focusing on mHealth technologies and diabetes
      management were included in the review if they were primary research papers
      published in academic journals and reported using a combination of qualitative
      and quantitative methods. The key data extracted from the reviewed studies
      include purpose of mixing, design type, stage of integration, methods of
      legitimation, and data collection techniques. RESULTS: The final sample (N=14)
      included studies focused on the feasibility and usability of mHealth diabetes
      apps (n=7), behavioral measures related to the mHealth apps (n=6), and challenges
      of intervention delivery in the mHealth context (n=1). Reviewed studies used
      advanced forms of mixed-methods designs where integration occurred at multiple
      points and data were collected using multiple techniques. However, the majority
      of studies did not identify a specific mixed-methods design or use accepted
      terminology; nor did they justify using this approach. CONCLUSIONS: This review
      provided important insights into the use of mixed methods in studies focused on
      diabetes management via mHealth technologies. The prominent role of qualitative
      methods and tailored measures in diabetes self-management studies was confirmed,
      and the importance of using multiple techniques and approaches in this field was
      emphasized. This review suggests defining specific mixed-methods questions, using
      specific legitimation methods, and developing research designs that overcome
      sampling and other methodological problems in future studies.

PMID- 30291053
TI  - Use of Social Media in the Diabetes Community: An Exploratory Analysis of
      Diabetes-Related Tweets.
AB  - BACKGROUND: Use of social media is becoming ubiquitous, and disease-related
      communities are forming online, including communities of interest around
      diabetes. OBJECTIVE: Our objective was to examine diabetes-related participation
      on Twitter by describing the frequency and timing of diabetes-related tweets, the
      geography of tweets, and the types of participants over a 2-year sample of 10% of
      all tweets. METHODS: We identified tweets with diabetes-related search terms and
      hashtags in a dataset of 29.6 billion tweets for the years 2013 and 2014 and
      extracted the text, time, location, retweet, and user information. We assessed
      the frequencies of tweets used across different search terms and hashtags by
      month and day of week and, for tweets that provided location information, by
      country. We also performed these analyses for a subset of tweets that used the
      hashtag #dsma, a social media advocacy community focused on diabetes. Random
      samples of user profiles in the 2 groups were also drawn and reviewed to
      understand the types of stakeholders participating online. RESULTS: We found
      1,368,575 diabetes-related tweets based on diabetes-related terms and hashtags.
      There was a seasonality to tweets; a higher proportion occurred during the month
      of November, which is when World Diabetes Day occurs. The subset of tweets with
      the #dsma were most frequent on Thursdays (coordinated universal time), which is
      consistent with the timing of a weekly chat organized by this online community.
      Approximately 2% of tweets carried geolocation information and were most
      prominent in the United States (on the east and west coasts), followed by
      Indonesia and the United Kingdom. For the user profiles randomly selected among
      overall tweets, we could not identify a relationship to diabetes for the majority
      of users; for the profiles using the #dsma hashtag, we found that patients with
      type 1 diabetes and their caregivers represented the largest proportion of
      individuals. CONCLUSIONS: Twitter is increasingly becoming a space for online
      conversations about diabetes. Further qualitative and quantitative content
      analysis is needed to understand the nature and purpose of these conversations.

PMID- 30291054
TI  - Data Mining of a Remote Behavioral Tracking System for Type 2 Diabetes Patients:
      A Prospective Cohort Study.
AB  - BACKGROUND: Complications from type 2 diabetes mellitus can be prevented when
      patients perform health behaviors such as vigorous exercise and glucose-regulated
      diet. The use of smartphones for tracking such behaviors has demonstrated success
      in type 2 diabetes management while generating repositories of analyzable digital
      data, which, when better understood, may help improve care. Data mining methods
      were used in this study to better understand self-monitoring patterns using
      smartphone tracking software. OBJECTIVE: Associations were evaluated between the
      smartphone monitoring of health behaviors and HbA1c reductions in a patient
      subsample with type 2 diabetes who demonstrated clinically significant benefits
      after participation in a randomized controlled trial. METHODS: A priori
      association-rule algorithms, implemented in the C language, were applied to app
      discretized use data involving three primary health behavior trackers (exercise,
      diet, and glucose monitoring) from 29 participants who achieved clinically
      significant HbA1c reductions. Use was evaluated in relation to improved HbA1c
      outcomes. RESULTS: Analyses indicated that nearly a third (9/29, 31%) of
      participants used a single tracker, half (14/29, 48%) used two primary trackers,
      and the remainder (6/29, 21%) of the participants used three primary trackers.
      Decreases in HbA1c were observed across all groups (0.97-1.95%), but clinically
      significant reductions were more likely with use of one or two trackers rather
      than use of three trackers (OR 0.18, P=.04). CONCLUSIONS: Data mining techniques
      can reveal relevant coherent behavior patterns useful in guiding future
      intervention structure. It appears that focusing on using one or two trackers, in
      a symbolic function, was more effective (in this sample) than regular use of all
      three trackers.

PMID- 30291055
TI  - Widely Viewed English Language YouTube Videos Relating to Diabetic Retinopathy: A
      Cross-Sectional Study.
AB  - BACKGROUND: An emergent source of information on health issues is the Internet.
      One such platform with 1 billion users is YouTube, the global video-sharing
      service. OBJECTIVE: The purpose of this study was to describe the content and
      characteristics of the most widely viewed YouTube videos related to diabetic
      retinopathy. METHODS: Videos were sorted according to number of views using the
      key words "diabetic retinopathy." For each video, general descriptive information
      was collected. This information included date and source of upload (news,
      professional, or consumer), length, and total number of views as of July 18,
      2016. Content categories were largely informed by a National Eye Institute fact
      sheet. Each video was viewed to determine which, if any, of the given content
      categories were present. RESULTS: Of the 98 most widely viewed videos related to
      diabetic retinopathy, 42 were generated by consumers, 40 were generated by
      professionals, and 16 were generated from news-based sources. The largest number
      of views were generated from professionals (624,770/994,494, 63.82%). Compared
      with professional videos, consumer videos were viewed less frequently (W=622,
      P=.04). The main purpose of the majority of videos was to provide information
      (59/98, 60%), and most of the videos showed or mentioned retinopathy in general
      (75/98, 77%). Smaller numbers offered information about specific types of
      retinopathy, namely proliferative (26/98, 27%) and nonproliferative (17/98, 17%).
      Compared with consumer-generated videos, professional videos were 5.57 times more
      likely to mention that diabetic retinopathy can go unnoticed (95% CI 1.59-26.15).
      More than 80% (80/98) of the most widely viewed videos did not address the
      asymptomatic nature of the disease, only about one-third (33/98) mentioned
      prevention, and only 58 of the 98 videos (59%) mentioned screening. CONCLUSION:
      Future research is needed to identify aspects of YouTube videos that attract
      viewer attention and best practices for using this medium to increase diabetic
      retinopathy screening among people with diabetes.

PMID- 30291056
TI  - Evaluating the Accuracy of Google Translate for Diabetes Education Material.
AB  - BACKGROUND: Approximately 21% of the US population speaks a language other than
      English at home; many of these individuals cannot effectively communicate in
      English. Hispanic and Chinese Americans, in particular, are the two largest
      minority groups having low health literacy in the United States. Fortunately,
      machine-generated translations represent a novel tool that non-English speakers
      can use to receive and relay health education information when human interpreters
      are not available. OBJECTIVE: The purpose of this study was to evaluate the
      accuracy of the Google Translate website when translating health information from
      English to Spanish and English to Chinese. METHODS: The pamphlet, "You are the
      heart of your family...take care of it," is a health education sheet for diabetes
      patients that outlines six tips for behavior change. Two professional translators
      translated the original English sentences into Spanish and Chinese. We recruited
      6 certified translators (3 Spanish and 3 Chinese) to conduct blinded evaluations
      of the following versions: (1) sentences translated by Google Translate, and (2)
      sentences translated by a professional human translator. Evaluators rated the
      sentences on four scales: fluency, adequacy, meaning, and severity. We performed
      descriptive analysis to examine differences between these two versions. RESULTS:
      Cronbach's alpha values exhibited high degrees of agreement on the rating outcome
      of both evaluator groups: .919 for the Spanish evaluators and .972 for the
      Chinese evaluators. The readability of the sentences in this study ranged from
      2.8 to 9.0 (mean 5.4, SD 2.7). The correlation coefficients between the grade
      level and translation accuracy for all sentences translated by Google were
      negative (eg, rMeaning=-.660), which indicates that Google provided accurate
      translation for simple sentences. However, the likelihood of incorrect
      translation increased when the original English sentences required higher grade
      levels to comprehend. The Chinese human translator provided more accurate
      translation compared to Google. The Spanish human translator, on the other hand,
      did not provide a significantly better translation compared to Google.
      CONCLUSION: Google produced a more accurate translation from English to Spanish
      than English to Chinese. Some sentences translated by Google from English to
      Chinese exhibit the potential to result in delayed patient care. We recommend
      continuous training and credential practice standards for professional medical
      translators to enhance patient safety as well as providing health education
      information in multiple languages.

PMID- 30291057
TI  - The Use of Mobile Health to Deliver Self-Management Support to Young People With
      Type 1 Diabetes: A Cross-Sectional Survey.
AB  - BACKGROUND: Young people living with type 1 diabetes face not only the challenges
      typical of adolescence, but also the challenges of daily management of their
      health and evolving understanding of the impact of their diagnosis on their
      future. Adolescence is a critical time for diabetes self-management, with a
      typical decline in glycemic control increasing risk for microvascular diabetes
      complications. To improve glycemic control, there is a need for evidence-based
      self-management support interventions that address the issues pertinent to this
      population, utilizing platforms that engage them. Increasingly, mobile health
      (mHealth) interventions are being developed and evaluated for this purpose with
      some evidence supporting improved glycemic control. A necessary step to enhance
      effectiveness of such approaches is to understand young people's preferences for
      this mode of delivery. OBJECTIVE: A cross-sectional survey was conducted to
      investigate the current and perceived roles of mHealth in supporting young people
      to manage their diabetes. METHODS: Young adults (16-24 years) with type 1
      diabetes in Auckland, New Zealand, were invited to take part in a survey via
      letter from their diabetes specialist. RESULTS: A total of 115 young adults
      completed the survey (mean age 19.5 years; male 52/115, 45%; European 89/115,
      77%), with all reporting they owned a mobile phone and 96% (110/115) of those
      were smartphones. However, smartphone apps for diabetes management had been used
      by only 33% (38/115) of respondents. The most commonly reported reason for not
      using apps was a lack of awareness that they existed. Although the majority felt
      they managed their diabetes well, 63% (72/115) reported wanting to learn more
      about diabetes and how to manage it. A total of 64% (74/115) respondents reported
      that they would be interested in receiving diabetes self-management support via
      text message (short message service, SMS). CONCLUSIONS: Current engagement with
      mHealth in this population appears low, although the findings from this study
      provide support for the use of mHealth in this group because of the ubiquity and
      convenience of mobile devices. mHealth has potential to provide information and
      support to this population, utilizing mediums commonplace for this group and with
      greater reach than traditional methods.

PMID- 30291058
TI  - Telemonitoring and Health Counseling for Self-Management Support of Patients With
      Type 2 Diabetes: A Randomized Controlled Trial.
AB  - BACKGROUND: The prevalence of diabetes is increasing among adults globally, and
      there is a need for new models of health care delivery. Research has shown that
      self-management approaches encourage persons with chronic conditions to take a
      primary role in managing their daily care. OBJECTIVE: The objective of this study
      was to investigate whether the introduction of a health technology-supported self
      management program involving telemonitoring and health counseling had beneficial
      effects on glycated hemoglobin (HbA1c), other clinical variables (height, weight,
      body mass index, blood pressure, blood lipid profile), and health-related quality
      of life (HRQoL), as measured using the Short Form Health Survey (SF-36) version 2
      in patients with type 2 diabetes. METHODS: This was a pragmatic randomized
      controlled trial of patients with type 2 diabetes. Both the control and
      intervention groups received usual care. The intervention group also participated
      in additional health promotion activities with the use of the Prescribed
      Healthcare Web application for self-monitoring of blood glucose and blood
      pressure. About every second month or when needed, the general practitioner or
      the diabetes nurse reviewed the results and the health care activity plan.
      RESULTS: A total of 166 patients with type 2 diabetes were randomly assigned to
      the intervention (n=87) or control (n=79) groups. From the baseline to follow-up,
      36 patients in the intervention group and 5 patients in the control group were
      lost to follow-up, and 2 patients died. Additionally, HbA1c was not available at
      baseline in one patient in the intervention group. A total of 122 patients were
      included in the final analysis after 19 months. There were no significant
      differences between the groups in the primary outcome HbA1c level (P=.33), and in
      the secondary outcome HRQoL as measured using SF-36. A total of 80% (67/87) of
      the patients in the intervention group at the baseline, and 98% (47/50) of the
      responders after 19-month intervention were familiar with using a personal
      computer (P=.001). After 19 months, nonresponders (ie, data from baseline)
      reported significantly poorer mental health in social functioning and role
      emotional subscales on the SF-36 (P=.03, and P=.01, respectively). CONCLUSIONS:
      The primary outcome HbA1c level and the secondary outcome HRQoL did not differ
      between groups after the 19-month follow-up. Those lost to follow-up reported
      significantly poorer mental health than did the responders in the intervention
      group. TRIAL REGISTRATION: Clinicaltrials.gov NCT01478672;
      https://clinicaltrials.gov/ct2/show/NCT01478672 (Archived by WebCite at
      http://www.webcitation.org/6r4eILeyu).

PMID- 30291059
TI  - One Drop | Mobile: An Evaluation of Hemoglobin A1c Improvement Linked to App
      Engagement.
AB  - BACKGROUND: Three recent reviews evaluated 19 studies testing the hemoglobin A1c
      (HbA1c) benefit of 16 diabetes apps, including 5 publicly available apps. Most
      studies relied on small samples and did not link app engagement with outcomes.
      OBJECTIVE: This study assessed both HbA1c change in a large sample of people
      using the One Drop | Mobile app and associations between app engagement and
      changes in HbA1c. METHODS: The One Drop | Mobile app for iOS and Android is
      designed to manually and passively (via Apple HealthKit, Google Fit, and the One
      Drop | Chrome blood glucose meter) store, track, and share data. Users can
      schedule medication reminders, view statistics, set goals, track health outcomes,
      and get data-driven insights. In June 2017, we queried data on people with
      diabetes using the app who had entered at least 2 HbA1c values in the app >60 and
      <=365 days apart. Multiple imputation corrected for missing data. Unadjusted and
      adjusted mixed effects repeated measures models tested mean HbA1c change by time,
      diabetes type, and their interaction. Multiple regression models assessed
      relationships between using the app to track food, activity, blood glucose, and
      medications and HbA1c change. RESULTS: The sample (N=1288) included people with
      type 1 diabetes (T1D) (n=367) or type 2 diabetes (T2D) (n=921) who were 35%
      female, diagnosed with diabetes for a mean 9.4 (SD 9.9) years, and tracked an
      average 1646.1 (SD 3621.9) self-care activities in One Drop | Mobile between
      their first (mean 8.14% [SD 2.06%]) and second HbA1c entry (mean 6.98% [SD
      1.1%]). HbA1c values were significantly associated with user-entered average
      blood glucose 90 days before the second HbA1c entry (rho=.73 to .75, P<.001).
      HbA1c decreased by an absolute 1.07% (unadjusted and adjusted F=292.03, P<.001)
      from first to second HbA1c entry. There was a significant interaction between
      diabetes type and HbA1c. Both groups significantly improved, but users with T2D
      had a greater HbA1c decrease over time than users with T1D (F=10.54, P<.001). For
      users with T2D (n=921), HbA1c decreased by an absolute 1.27% (F=364.50, P<.001)
      from first to second HbA1c entry. Finally, using One Drop | Mobile to record food
      was associated with greater HbA1c reductions even after adjusting for covariates
      and after also adjusting for insulin use for users with T2D (all P<.05).
      CONCLUSIONS: People with T1D and T2D reported a 1.07% to 1.27% absolute reduction
      in HbA1c during a median 4 months of using the One Drop | Mobile app. Using the
      app to track self-care was associated with improved HbA1c. More research is
      needed on the health benefits of publicly available diabetes apps, particularly
      studies associating app engagement with short- and long-term effects.

PMID- 30291060
TI  - The Effect of Telehealth on Quality of Life and Psychological Outcomes Over a 12
      Month Period in a Diabetes Cohort Within the Whole Systems Demonstrator Cluster
      Randomized Trial.
AB  - BACKGROUND: Much is written about the promise of telehealth and there is great
      enthusiasm about its potential. However, many studies of telehealth do not meet
      orthodox quality standards and there are few studies examining quality of life in
      diabetes as an outcome. OBJECTIVE:  To assess the impact of home-based telehealth
      (remote monitoring of physiological, symptom and self-care behavior data for long
      term conditions) on generic and disease-specific health-related quality of life,
      anxiety, and depressive symptoms over 12 months in patients with diabetes. Remote
      monitoring provides the potential to improve quality of life, through the
      reassurance it provides patients. METHODS: The study focused on participant
      reported outcomes of patients with diabetes within the Whole Systems Demonstrator
      (WSD) Telehealth Questionnaire Study, nested within a pragmatic cluster
      randomized trial of telehealth (the WSD Telehealth Trial), held across 3 regions
      of England. Telehealth was compared with usual-care, with general practice as the
      unit of randomization. Participant-reported outcome measures (Short-Form 12,
      EuroQual-5D, Diabetes Health Profile scales, Brief State-Trait Anxiety Inventory,
      and Centre for Epidemiological Studies Depression Scale) were collected at
      baseline, short-term (4 months) and long-term (12months) follow-ups. Intention-to
      treat analyses testing treatment effectiveness, were conducted using multilevel
      models controlling for practice clustering and a range of covariates. Analyses
      assumed participants received their allocated treatment and were conducted for
      participants who completed the baseline plus at least one follow-up assessment
      (n=317). RESULTS:  Primary analyses showed differences between telehealth and
      usual care were small and only reached significance for 1 scale (diabetes health
      profile-disinhibited eating, P=.006). The magnitude of differences between trial
      arms did not reach the trial-defined minimal clinically important difference of
      0.3 standard deviations for most outcomes. Effect sizes (Hedge's g) ranged from
      0.015 to 0.143 for Generic quality of life (QoL) measures and 0.018 to 0.394 for
      disease specific measures. CONCLUSIONS: Second generation home-based telehealth
      as implemented in the WSD evaluation was not effective in the subsample of people
      with diabetes. Overall, telehealth did not improve or have a deleterious effect
      quality of life or psychological outcomes for patients with diabetes over a 12
      month period.

PMID- 30291061
TI  - The Value of Children's Voices for a Video Game Development in the Context of
      Type 1 Diabetes: Focus Group Study.
AB  - BACKGROUND: Children with type 1 diabetes mellitus (T1DM) face daily challenges
      performing self-care tasks, controlling symptoms, and dealing with psychosocial
      issues. The use of video games to improve health is a successful support for
      persons with chronic diseases, promoting adequate self-management through
      simulations of real life. Involving future users in the development of games is
      essential to generating innovative, creative, and effective programs. OBJECTIVE:
      Our goal is to identify what children with T1DM need to know about their disease
      and their self-care tasks as well as their preferences in video games. METHODS:
      Children with T1DM provided input about their learning needs, self-care tasks,
      and preferences in video games. Three categories were identified through
      qualitative content analysis: dealing with emotions and knowledge, practical
      skills and awareness, and game preferences. RESULTS: Children expressed concerns
      about the difficulties of self-care, lack of knowledge about diabetes, and lack
      of awareness about the consequences of behaviors related to self-care, which
      contribute to inappropriate behaviors and significantly impact self-management of
      their disease. They expressed enthusiasm for a video game for children with
      diabetes that considered their needs and preferences. CONCLUSIONS: Findings
      support the potential benefits when children's input is considered in game
      design. Consideration of customer needs and preferences is a powerful resource in
      the development of video games with enhanced learning experience.

PMID- 30291062
TI  - A Novel Intervention Including Individualized Nutritional Recommendations Reduces
      Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes.
AB  - BACKGROUND: Type 2 diabetes (T2D) is typically managed with a reduced fat diet
      plus glucose-lowering medications, the latter often promoting weight gain.
      OBJECTIVE: We evaluated whether individuals with T2D could be taught by either on
      site group or remote means to sustain adequate carbohydrate restriction to
      achieve nutritional ketosis as part of a comprehensive intervention, thereby
      improving glycemic control, decreasing medication use, and allowing clinically
      relevant weight loss. METHODS: This study was a nonrandomized, parallel arm,
      outpatient intervention. Adults with T2D (N=262; mean age 54, SD 8, years; mean
      body mass index 41, SD 8, kg.m-2; 66.8% (175/262) women) were enrolled in an
      outpatient protocol providing intensive nutrition and behavioral counseling,
      digital coaching and education platform, and physician-guided medication
      management. A total of 238 participants completed the first 10 weeks. Body
      weight, capillary blood glucose, and beta-hydroxybutyrate (BOHB) levels were
      recorded daily using a mobile interface. Hemoglobin A1c (HbA1c) and related
      biomarkers of T2D were evaluated at baseline and 10-week follow-up. RESULTS:
      Baseline HbA1c level was 7.6% (SD 1.5%) and only 52/262 (19.8%) participants had
      an HbA1c level of <6.5%. After 10 weeks, HbA1c level was reduced by 1.0% (SD
      1.1%; 95% CI 0.9% to 1.1%, P<.001), and the percentage of individuals with an
      HbA1c level of <6.5% increased to 56.1% (147/262). The majority of participants
      (234/262, 89.3%) were taking at least one diabetes medication at baseline. By 10
      weeks, 133/234 (56.8%) individuals had one or more diabetes medications reduced
      or eliminated. At follow-up, 47.7% of participants (125/262) achieved an HbA1c
      level of <6.5% while taking metformin only (n=86) or no diabetes medications
      (n=39). Mean body mass reduction was 7.2% (SD 3.7%; 95% CI 5.8% to 7.7%, P<.001)
      from baseline (117, SD 26, kg). Mean BOHB over 10 weeks was 0.6 (SD 0.6) mmol.L-1
      indicating consistent carbohydrate restriction. Post hoc comparison of the remote
      versus on-site means of education revealed no effect of delivery method on change
      in HbA1c (F1,260=1.503, P=.22). CONCLUSIONS: These initial results indicate that
      an individualized program delivered and supported remotely that incorporates
      nutritional ketosis can be highly effective in improving glycemic control and
      weight loss in adults with T2D while significantly decreasing medication use.

PMID- 30291063
TI  - Improving Glycemic Control With a Standardized Text-Message and Phone-Based
      Intervention: A Community Implementation.
AB  - BACKGROUND: Type II diabetes mellitus (T2DM) presents a major disease burden in
      the United States. Outpatient glycemic control among patients with T2DM remains
      difficult. Telemedicine shows great potential as an adjunct therapy to aid in
      glycemic control in real-world settings. OBJECTIVE: We aimed to explore the
      effectiveness of EpxDiabetes, a novel digital health intervention, in improving
      hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) among patients with
      uncontrolled diabetes. METHODS: We recruited 396 patients from a community clinic
      in St. Louis, Missouri, from a database of patients diagnosed with T2DM and with
      a most recent HbA1c >7% as part of a quality improvement project. An automated
      call or text-messaging system was used to monitor patient-reported FBG. If
      determined to be elevated, care managers were notified by email, text, or
      electronic medical record alert. Participants self-reported their FBG data by
      replying to EpxDiabetes automated phone calls or text messages. Data were
      subsequently analyzed, triaged, and shared with providers to enable appropriate
      follow-up and care plan adjustments. Absolute HbA1c reduction, patient
      engagement, and absolute patient-reported FBG reduction were examined at
      approximately 6 months post implementation. RESULTS: EpxDiabetes had an average
      95.6% patient response rate to messages at least once per month and an average
      71.1% response rate to messages at least once per week. Subsequent HbA1c drop
      with EpxDiabetes use over 4 months was -1.15% (95% CI -1.58 to -0.71) for
      patients with HbA1c >8% at baseline compared to the change in HbA1c over 4 months
      prior to the implementation of EpxDiabetes of only -0.005 points (95% CI -0.28 to
      0.27), P=.0018. CONCLUSIONS: EpxDiabetes may help reduce HbA1c in patients with
      high HbA1c baselines (>8%). The intervention demonstrates high patient engagement
      sustainable for at least 6 months.

PMID- 30291064
TI  - Impact of Facebook on Glucose Control in Type 1 Diabetes: A Three-Year Cohort
      Study.
AB  - BACKGROUND: As the world is changing, traditional health care services should be
      adapted for the new era of technology and the Internet. One of the possible ways
      for communication between health care providers and patients is social media.
      There are several benefits of social media in health: increased interactions with
      others; more available and shared information; increased accessibility; social or
      emotional support. OBJECTIVE: The aim of this study was to evaluate the results
      of Facebook and CareLink software as a possible Internet tool to improve diabetes
      control in type 1 diabetes patients using a sensor augmented pump. METHODS: A
      total of 67 adolescents with type 1 diabetes and in the age range of 14-23 years
      were randomized in 2 groups: (1) Traditional group and (2) Internet group. In the
      traditional group, 34 patients were treated using standard medical protocol with
      regular clinic visits, where data were uploaded at the clinic and interventions
      (pump settings-basal bolus insulin and education) were delivered to the patient.
      In the Internet group, 33 patients were treated using Facebook and CareLink
      software (Medtronic Diabetes) on a monthly basis, where the data were uploaded by
      the patient at home and interventions (same as traditional group) were delivered
      via Facebook (written reports and chats). Both the traditional and Internet group
      had regular visits every 3 months with standard medical protocol. Glycosylated
      hemoglobin (HbA1c) was obtained before and every 3 months during the study for a
      3-year-period. RESULTS: The improvement in glucose control was found in both
      groups: 7.9% (SD 1.4) [62.8 mmol/mol (SD 12.9)] to 6.9% (SD 1.2) [51.9 mmol/mol
      (SD 10.8)] in the traditional group, and 7.8% (SD 1.8) [61.7 mmol/mol (SD 17.2)]
      to 6.7% (SD 1.8) [49.7 mmol/mol (SD 17.3)] in the Internet group). Significant
      improvement of HbA1c (P<.05) was found in favor of the Internet group.
      CONCLUSIONS: Social media such as Facebook as a tool can assist in standard
      medical care to improve glucose control in a long term period in adolescents with
      type 1 diabetes using insulin pump therapy.

PMID- 30291065
TI  - Examining the Impact of a Novel Blood Glucose Monitor With Color Range Indicator
      on Decision-Making in Patients With Type 1 and Type 2 Diabetes and its
      Association With Patient Numeracy Level.
AB  - BACKGROUND: Many patients struggle to interpret and respond appropriately to the
      numerical blood glucose results displayed on their meter, with many regularly
      taking no action or self-care adjustment for out-of-range results. We recently
      reported that a glucose meter that provides automatic onscreen information using
      a color range indicator (ColorSure Technology) improved the ability of patients
      to categorize their blood glucose results. OBJECTIVE: The objective of this study
      was to examine how ColorSure Technology (or color) affected patient decision
      making on blood glucose results and how patient numeracy levels influenced such
      decisions. METHODS: We invited 103 subjects (56 with type 2 diabetes and 47 with
      type 1 diabetes) to a face-to-face in-clinic visit in a diabetes care center and
      showed them glucose results with or without color via interactive computer or
      paper logbook exercises. Before participating in these exercises, subjects
      completed surveys on numeracy and their understanding of blood glucose
      information. RESULTS: Subjects preferentially acted on high glucose results shown
      with color (55%, 57/103) compared to results without color (45%, 46/103; P=.001).
      When shown identical pairs of results, subjects preferentially acted on results
      shown with color (62%, 64/103) compared to results without color (16%, 16/103)
      (P<.001). Subjects more accurately identified days of the week in which results
      were low, in range, or high when reviewing logbooks with color (83%, 85/103) than
      without color (68%, 70/103; P=.012). Subjects with lower numeracy were more
      likely to consider taking action for high glucose results shown with color (59%,
      18/31) than without color (41%, 13/31) and preferentially would take action on
      results shown with color (71%, 22/31) compared to results without color (16%,
      5/31). CONCLUSIONS: Insulin- and noninsulin-using subjects were each more
      inclined to act when glucose results were shown with color, and associating
      glucose results with color was viewed as particularly beneficial by subjects with
      lower numeracy.

PMID- 30291066
TI  - How's Your Sugar? Evaluation of a Website for Aboriginal People With Diabetes.
AB  - BACKGROUND: Australia's Aboriginal and Torres Strait Islander peoples (hereafter
      referred to as "Aboriginal people") have the longest continuing culture in the
      world, living sustainably for at least 65,000 years on the Australian continent.
      In relatively recent times, colonization processes have resulted in Aboriginal
      people experiencing unacceptable health inequalities compared with other
      Australians. One disease introduced due to colonization is diabetes, the second
      leading cause of death for Aboriginal peoples. OBJECTIVES: The objective of this
      study was to describe the construction and utilization of the website "How's Your
      Sugar, " a website for Aboriginal people with type 2 diabetes (herein after
      referred to as diabetes). The questions for the evaluation were as follows: how
      was the website constructed; did target groups utilize the website; and did
      engagement with the website improve diabetes management. METHODS: A mixed-method
      study design was employed. A content analysis of project documents provided
      information about the website construction. Data from Google analytics provided
      information about website utilization. To describe patterns of website sessions,
      percentages and numbers were calculated. A voluntary survey provided more
      information on website utilization and diabetes self-management. Percentage,
      numbers, and 95% CIs were calculated for each variable. A chi-square test was
      performed for Aboriginal status, age, gender, and Aboriginal diabetic status
      using Australian population estimates and Aboriginal diabetes rates. RESULTS: The
      website development drew on Aboriginal health, social marketing, interactive
      health promotion frameworks, as well as evidence for diabetes self-management.
      The website build involved a multidisciplinary team and participation of
      Aboriginal diabetics, Aboriginal diabetic family members, and Aboriginal health
      workers. This participation allowed for inclusion of Aboriginal ways of knowing
      and being. The highest number of website sessions came from Australia, 98.15%
      (47,717/48,617) and within Australia, Victoria 50.97% (24,323/47,717). There were
      129 survey respondents, and the distribution had more female, 82.9% (107/129, 95%
      CI 76-88), Aboriginal, 21.7% (28/129, 95% CI 16-30), and Aboriginal diabetic, 48%
      (13/27, 95% CI 31-66) respondents than expected with P<.001 for these three
      groups. Most common reasons for visits were university assignment research, 40.6%
      (41/101), and health workers looking for information, 20.8% (21/101). The sample
      size was too small to calculate diabetes self-management change. CONCLUSIONS:
      Inclusion of Aboriginal ways of knowing and being alongside other theoretical and
      evidence models in Web design is possible. Aboriginal people do utilize Web-based
      health promotion, and further understanding about reaching to this population
      would be of use. Provision of an education resource would likely have enhanced
      educational engagement. Web-based technologies are rapidly evolving, and these
      can potentially measure behavior change in engaging ways that also have benefits
      for the participant. A challenge for designers is inclusivity of cultural
      diversity for self-determination.

PMID- 30291067
TI  - Mutual Involvement in Families With Type 2 Diabetes Through Web-Based Health Care
      Solutions: Quantitative Survey Study of Family Preferences, Challenges, and
      Potentials.
AB  - BACKGROUND: Type 2 diabetes (T2D) is a prevalent chronic disease that affects not
      just patients but entire families. Both the patient and the rest of the family
      may benefit from gaining knowledge about the disease and from supportive
      interfamilial interaction. The Internet is becoming a widely-used resource for
      health information, so a Web-based solution could potentially promote awareness
      and knowledge on how to manage T2D as a family, while also providing support for
      the family. OBJECTIVE: We aim to assess the usage of online diabetes information
      by patients with T2D and their relatives, and explore the families' needs and
      preferences regarding online information on diabetes. METHODS: A quantitative
      self-reported questionnaire survey was performed with Danish families that had at
      least one family member diagnosed with T2D. The survey consisted of 36 closed
      questions on demographics, usage of the Internet, preferences in the source of
      information, interest in online information on six problem domains within family
      life related to T2D, preferences towards the delivery format of online
      information, and peer-to-peer communication. Two open-ended questions were also
      included to elicit any additional comments or suggestions about improving online
      information on T2D regarding family life. RESULTS: Fifty participants from 22
      families with T2D answered the questionnaire individually. Relatives (25/28, 89%)
      and patients (22/22, 100%) indicated that information on T2D is relevant for
      them, while indicating that the Internet is the first or second preferred source
      when in need of information on T2D (25/28, 89% vs 21/22, 95%). Only a minority of
      the participants indicated that they had searched the Internet to gain knowledge
      on T2D regarding family life (9/28, 32% vs 10/22, 46%). Also, patients were more
      likely to have used the Internet to gain information on T2D (P=.027). Both groups
      indicated a preference for watching videos or reading about T2D in relation to
      family life while a minority of the participants indicated an interest in peer-to
      peer communication. Regarding the six problem domains, the domains Support,
      Knowledge, and Everyday Life were slightly more popular. These three domains were
      considered interesting by at least 79% (22/28) and 73% (16/22) of the relatives
      and patients respectively, while the domains Communication, Worries, and Roles
      were considered interesting by at least 46% (20/28) and 50% (11/22). CONCLUSIONS:
      Despite an interest in online information on T2D, there appears to be an
      unsatisfied need for more supportive online information on T2D aimed at Danish
      families with T2D. Based on family preferences, online information should focus
      on the six problem domains and be presented through text and videos by health
      care practitioners and peers. Peer-to-peer communication elements may be
      beneficial, but are only expected to be used by a very limited number of
      families.

PMID- 30291068
TI  - A Feasible and Efficacious Mobile-Phone Based Lifestyle Intervention for Filipino
      Americans with Type 2 Diabetes: Randomized Controlled Trial.
AB  - BACKGROUND: Filipino Americans have a high prevalence of obesity, type 2 diabetes
      (T2D), and cardiovascular disease compared with other Asian American subgroups
      and non-Hispanic whites. Mobile health (mHealth) weight loss interventions can
      reduce chronic disease risks, but these are untested in Filipino Americans with
      T2D. OBJECTIVE: The objective of this study was to assess feasibility and
      potential efficacy of a pilot, randomized controlled trial (RCT) of a culturally
      adapted mHealth weight loss lifestyle intervention (Pilipino Americans Go4Health
      [PilAm Go4Health]) for overweight Filipino Americans with T2D. METHODS: This was
      a 2-arm pilot RCT of the 3-month PilAm Go4Health intervention (phase 1) with an
      active waitlist control and 3-month follow-up (phase 2). The waitlist control
      received the PilAm Go4Health in phase 2, whereas the intervention group
      transitioned to the 3-month follow-up. PilAm Go4Health incorporated a Fitbit
      accelerometer, mobile app with diary for health behavior tracking (steps,
      food/calories, and weight), and social media (Facebook) for virtual social
      support, including 7 in-person monthly meetings. Filipino American adults >=18
      years with T2D were recruited from Northern California. Feasibility was measured
      by rates of recruitment, engagement, and retention. Multilevel regression
      analyses assessed within and between group differences for the secondary outcome
      of percent weight change and other outcomes of weight (kg), body mass index
      (BMI), waist circumference, fasting plasma glucose, HbA1c, and steps. RESULTS: A
      total of 45 Filipino American adults were enrolled and randomized. Mean age was
      58 (SD 10) years, 62% (28/45) were women, and mean BMI was 30.1 (SD 4.6).
      Participant retention and study completion were 100%, with both the intervention
      and waitlist group achieving near-perfect attendance at all 7 intervention office
      visits. Groups receiving the PilAm Go4Health in phase 1 (intervention group) and
      phase 2 (waitlist group) had significantly greater weight loss, -2.6% (-3.9 to 
      1.4) and -3.3% (-1.8 to -4.8), respectively, compared with the nonintervention
      group, resulting in a moderate to small effect sizes (d=0.53 and 0.37,
      respectively). In phase 1, 18% (4/22) of the intervention group achieved a 5%
      weight loss, whereas 82% (18/22) maintained or lost 2% to 5% of their weight and
      continued to maintain this weight loss in the 3-month follow-up. Other health
      outcomes, including waist circumference, BMI, and step counts, improved when each
      arm received the PilAm Go4Health, but the fasting glucose and HbA1c outcomes were
      mixed. CONCLUSIONS: The PilAm Go4Health was feasible and demonstrated potential
      efficacy in reducing diabetes risks in overweight Filipino Americans with T2D.
      This study supports the use of mHealth and other promising intervention
      strategies to reduce obesity and diabetes risks in Filipino Americans. Further
      testing in a full-scale RCT is warranted. These findings may support intervention
      translation to reduce diabetes risks in other at-risk diverse populations. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT02290184;
      https://clinicaltrials.gov/ct2/show/NCT02290184 (Archived by WebCite at
      http://www.webcitation.org/6vDfrvIPp).

PMID- 30291069
TI  - New-Onset Diabetes Educator to Educate Children and Their Caregivers About
      Diabetes at the Time of Diagnosis: Usability Study.
AB  - BACKGROUND: Diabetes self-management education is essential at the time of
      diagnosis. We developed the New-Onset Diabetes Educator (NODE), an animation
      based educational web application for type 1 diabetes mellitus patients.
      OBJECTIVE: Our hypothesis is that NODE is a feasible, effective and user-friendly
      intervention in improving diabetes self-management education delivery to
      child/caregiver-dyads at the time of diagnosis. METHODS: We used a pragmatic
      parallel randomized trial design. Dyads were recruited within 48 hours of
      diagnosis and randomized into a NODE-enhanced diabetes self-management education
      or a standard diabetes self-management education group. Dyads randomized in the
      NODE group received the intervention on an iPad before receiving the standard
      diabetes self-management education with a nurse educator. The Diabetes Knowledge
      Test 2 assessed disease-specific knowledge pre- and postintervention in both
      groups, and was compared using t tests. Usability of the NODE mobile health
      intervention was assessed in the NODE group. RESULTS: We recruited 16 dyads (mean
      child age 10.75, SD 3.44). Mean Diabetes Knowledge Test 2 scores were 14.25 (SD
      4.17) and 18.13 (SD 2.17) pre- and postintervention in the NODE group, and 15.50
      (SD 2.67) and 17.38 (SD 2.26) in the standard diabetes self-management education
      group. The effect size was medium (Delta=0.56). Usability ratings of NODE were
      excellent. CONCLUSIONS: NODE is a feasible mobile health strategy for type 1
      diabetes education. It has the potential to be an effective and scalable tool to
      enhance diabetes self-management education at time of diagnosis, and
      consequently, could lead to improved long-term clinical outcomes for patients
      living with the disease.

PMID- 30291070
TI  - Mobile App for Simplifying Life With Diabetes: Technical Description and
      Usability Study of GlucoMan.
AB  - BACKGROUND: Patients with diabetes can be affected by several comorbidities that
      require immediate action when occurring as they may otherwise cause fatal or
      consequential damage. For this reason, patients must closely monitor their
      metabolism and inject insulin when necessary. The documentation of glucose values
      and other relevant measurements is often still on paper in a diabetes diary.
      OBJECTIVE: The goal of this work is to develop and implement a novel mobile
      health system for the secure collection of relevant data referring to a person's
      metabolis and to digitize the diabetes diary to enable continuous monitoring for
      both patients and treating physicians. One specific subgoal is to enable data
      transmission of health parameters to secure data storage. METHODS: The process of
      implementing the system consists of (1) requirements analysis with patients and
      physicians to identify patient needs and specify relevant functionalities, (2)
      design and development of the app and the data transmission, and (3) usability
      study. RESULTS: We developed and implemented the mobile app GlucoMan to support
      data collection pertaining to a person's metabolism. An automated transfer of
      measured values from a glucometer was implemented. Medication and nutrition data
      could be entered using product barcodes. Relevant background knowledge such as
      information on carbohydrates was collected from existing databases. The recorded
      data was transmitted using international interoperability standards to the
      MIDATA.coop storage platform. The usability study revealed some design issues
      that needs to be solved, but in principle, the study results show that the app is
      easy to use and provides useful features. CONCLUSIONS: Data collection on a
      patient's metabolism can be supported with a multifunctional app such as
      GlucoMan. Besides monitoring, continuous data can be documented and made
      available to the treating physician. GlucoMan allows patients to monitor disease
      relevant parameters and decide who accesses their health data. In this way,
      patients are empowered not only to manage diabetes but also manage their health
      data.

PMID- 30291071
TI  - Health Care Professionals' Clinical Perspectives on Glycemic Control and
      Satisfaction With a New Blood Glucose Meter With a Color Range Indicator: Online
      Evaluation in India, Russia, China, and the United States.
AB  - BACKGROUND: We previously demonstrated in patients with diabetes that displaying
      blood glucose results in association with color improved their ability to
      interpret glucose results. OBJECTIVE: The objective of this study was to
      investigate the perceptions of health care professionals (HCPs) in specific
      countries about the value of color on a new glucose meter and to determine if HCP
      perspectives among countries differ on the value of this approach in clinical
      practice. METHODS: A total of 180 HCPs, including 105 endocrinologists, 34
      primary care physicians, 25 diabetes educators, and 16 pharmacists, were
      recruited from India (n=50), Russia (n=50), China (n=50), and the United States
      (n=30). These HCPs experienced the OneTouch Select Plus Simple glucose meter
      online from their own office computer using interactive demonstrations (webpages,
      meter simulator, and video clips). After providing demographic and current
      clinical practice insights, HCPs responded to questions about the utility of the
      color-enhanced glucose meter. RESULTS: Mean age and years in their current
      professional role for the 180 HCPs was 41.3 (SD 8.1) and 13.3 (SD 6.8) years for
      endocrinologists, 41.3 (SD 8.3) and 14.1 (SD 6.8) years for primary care
      physicians, 37.5 (SD 8.7) and 12.7 (SD 6.8) years for diabetes educators, and
      35.9 (SD 5.3) and 9.5 (SD 5.2) years for pharmacists. In all, 88% (44/50) of
      Russian and 83% (25/30) of American HCPs said their patients find it easy to
      recognize low, in-range, or high blood glucose results compared to 56% (28/50) of
      HCPs in China and 42% (21/50) in India. Regardless of country, HCPs had less
      confidence that their patients act on blood glucose results with 52% (26/50) in
      Russia, 63% (19/30) in the United States, 60% (30/50) in China, and 40% (20/50)
      in India responding positively. During the interactive online meter experience,
      HCPs from all countries responded positively to questions about a meter with
      color features. After reflecting on the value of this meter, most HCPs strongly
      agreed or agreed their patients would be more inclined to act on results using a
      meter with color features (Russia: 92%, 46/50; United States: 70%, 21/30; China:
      98%, 49/50; India: 94%, 47/50). They also said that color was particularly useful
      for patients with lower numeracy or education who may struggle with interpreting
      results (Russia: 98%, 49/50; United States: 77%, 23/30; China: 100%, 50/50;
      India: 82%, 41/50). CONCLUSIONS: This multicountry online study provides evidence
      that HCPs had high overall satisfaction with the OneTouch Select Plus glucose
      meter, which uses color-coded information to assist patients with interpreting
      blood glucose results. This may be especially helpful in patient populations with
      low numeracy or literacy and limited access to health care and direct interaction
      with HCPs.

PMID- 30291072
TI  - Assessing Diabetes-Relevant Data Provided by Undergraduate and Crowdsourced Web
      Based Survey Participants for Honesty and Accuracy.
AB  - BACKGROUND: To eliminate health disparities, research will depend on our ability
      to reach select groups of people (eg, samples of a particular racial or ethnic
      group with a particular disease); unfortunately, researchers often experience
      difficulty obtaining high-quality data from samples of sufficient size.
      OBJECTIVE: Past studies utilizing MTurk applaud its diversity, so our initial
      objective was to capitalize on MTurk's diversity to investigate psychosocial
      factors related to diabetes self-care. METHODS: In Study 1, a "Health Survey" was
      posted on MTurk to examine diabetes-relevant psychosocial factors. The survey was
      restricted to individuals who were 18 years of age or older with diabetes.
      Detection of irregularities in the data, however, prompted an evaluation of the
      quality of MTurk health-relevant data. This ultimately led to Study 2, which
      utilized an alert statement to improve conscientious behavior, or the likelihood
      that participants would be thorough and diligent in their responses. Trap
      questions were also embedded to assess conscientious behavior. RESULTS: In Study
      1, of 4165 responses, 1246 were generated from 533 unique IP addresses completing
      the survey multiple times within close temporal proximity. Ultimately, only 252
      responses were found to be acceptable. Further analyses indicated additional
      quality concerns with this subsample. In Study 2, as compared with the MTurk
      sample (N=316), the undergraduate sample (N=300) included more females, and fewer
      individuals who were married. The samples did not differ with respect to race.
      Although the presence of an alert resulted in fewer trap failures (mean=0.07)
      than when no alert was present (mean=0.11), this difference failed to reach
      significance: F1,604=2.5, P=.11, n2=.004, power=.35. The modal trap failure
      response was zero, while the mean was 0.092 (SD=0.32). There were a total of 60
      trap failures in a context where the potential could have exceeded 16,000.
      CONCLUSIONS: Published studies that utilize MTurk participants are rapidly
      appearing in the health domain. While MTurk may have the potential to be more
      diverse than an undergraduate sample, our efforts did not meet the criteria for
      what would constitute a diverse sample in and of itself. Because some researchers
      have experienced successful data collection on MTurk, while others report
      disastrous results, Kees et al recently identified that one essential area of
      research is of the types and magnitude of cheating behavior occurring on Web
      based platforms. The present studies can contribute to this dialogue, and
      alternately provide evidence of disaster and success. Moving forward, it is
      recommended that researchers employ best practices in survey design and
      deliberately embed trap questions to assess participant behavior. We would
      strongly suggest that standards be in place for publishing the results of Web
      based surveys-standards that protect against publication unless there are
      suitable quality assurance tests built into the survey design, distribution, and
      analysis.

PMID- 30291073
TI  - A Novel Approach to Identifying Barriers and Facilitators in Raising a Child With
      Type 1 Diabetes: Qualitative Analysis of Caregiver Blogs.
AB  - BACKGROUND: With rising incidence of type 1 diabetes (T1D) diagnoses among
      children and the high levels of distress experienced by the caregivers of these
      children, caregiver support is becoming increasingly important. Historically,
      relatively few support resources have existed. Increasing use of the Internet,
      and blogs in particular, has seen a growth of peer support between caregivers of
      children with T1D. However, little is known about the type and quality of
      information shared on T1D caregiver blogs. At the same time, the information on
      such blogs offers a new window into what challenges and successes caregivers
      experience in helping to manage their children's T1D. OBJECTIVE: The purpose of
      this study was to (1) analyze blogs of caregivers to children with T1D to better
      understand the challenges and successes they face in raising a child with T1D,
      and (2) assess the blogs for the presence of unsafe or inaccurate clinical
      information or advice. METHODS: An inductive thematic qualitative study was
      conducted of three blogs authored by caregivers of children living with T1D,
      which included 140 unique blog posts and 663 associated comments. Two physician
      investigators evaluated the blogs for presence of clinical or medical
      misinformation. RESULTS: Five major themes emerged: (1) the impact of the child's
      diagnosis, (2) the burden of intense self-management experienced in caring for a
      child with T1D, (3) caregivers' use of technology to ease their fear of
      hypoglycemia and impacts that device alarms associated with this technology have
      on caregiver burden, (4) caregivers' perceptions of frequently missed or delayed
      diagnosis of T1D and the frustration this causes, and (5) the resilience that
      caregivers develop despite the burdens they experience. Misinformation was
      exceedingly rare and benign when it did occur. CONCLUSIONS: Blog analysis
      represents a novel approach to understand the T1D caregiver's experience. This
      qualitative study found many challenges that caregivers face in raising a child
      with T1D. Despite the many barriers caregivers face in managing their children's
      T1D, they find support through advocacy efforts and peer-to-peer blogging. Blogs
      provide a unique avenue for support, with only rare and benign findings of
      medical misinformation, and may be a resource that diabetes care providers can
      consider offering to families for support.

PMID- 30291074
TI  - Change in Glycemic Control With Use of a Digital Therapeutic in Adults With Type
      2 Diabetes: Cohort Study.
AB  - BACKGROUND: Intensive lifestyle change can treat and even reverse type 2
      diabetes. Digital therapeutics have the potential to deliver lifestyle as
      medicine for diabetes at scale. OBJECTIVE: This 12-week study investigates the
      effects of a novel digital therapeutic, FareWell, on hemoglobin A1c (HbA1c) and
      diabetes medication use. METHODS: Adults with type 2 diabetes and a mobile phone
      were recruited throughout the United States using Facebook advertisements. The
      intervention aim was to effect a sustainable shift to a plant-based dietary
      pattern and regular exercise by advancing culinary literacy and lifestyle skill
      acquisition. The intervention was delivered by an app paired with specialized
      human support, also delivered digitally. Health coaching was provided every 2
      weeks by telephone, and a clinical team was available for participants requiring
      additional support. Participants self-reported current medications and HbA1c at
      the beginning and end of the 12-week program. Self-efficacy related to managing
      diabetes and maintaining dietary changes was assessed via survey. Engagement was
      recorded automatically through the app. RESULTS: We enrolled 118 participants
      with a baseline HbA1c >6.5%. Participants were 81.4% female (96/118) and resided
      in 38 US states with a mean age of 50.7 (SD 9.4) years, baseline body mass index
      of 38.1 (SD 8.8) kg/m2, and baseline HbA1c of 8.1% (SD 1.6). At 12 weeks, 86.2%
      (94/109) of participants were still using the app. Mean change in HbA1c was -0.8%
      (97/101, SD 1.3, P<.001) for those reporting end-study data. For participants
      with a baseline HbA1c >7.0% who did not change medications midstudy, HbA1c change
      was -1.1% (67/69, SD 1.4, P<.001). The proportion of participants with an end
      study HbA1c <6.5% was 28% (22/97). After completion of the intervention, 17%
      (16/97) of participants reported a decrease in diabetic medication while 8%
      (8/97) reported an increase. A total of 57% (55/97) of participants achieved a
      composite outcome of reducing HbA1c, reducing diabetic medication use, or both;
      92% (90/98) reported greater confidence in their ability to manage their diabetes
      compared to before the program, and 91% (89/98) reported greater confidence in
      their ability to maintain a healthy dietary pattern. Participants engaged with
      the app an average of 4.3 times per day. We observed a significantly greater
      decrease in HbA1c among participants in the highest tertile of app engagement
      compared to those in the lowest tertile of app engagement (P=.03). CONCLUSIONS:
      Clinically meaningful reductions in HbA1c were observed with use of the FareWell
      digital therapeutic. Greater glycemic control was observed with increasing app
      engagement. Engagement and retention were both high in this widely distributed
      sample.

PMID- 30291075
TI  - Perceptions of Persons With Type 2 Diabetes Treated in Swedish Primary Health
      Care: Qualitative Study on Using eHealth Services for Self-Management Support.
AB  - BACKGROUND: Digital health services are increasing rapidly worldwide. Strategies
      to involve patients in self-monitoring of type 2 diabetes (T2D) on a daily basis
      is of crucial importance, and there is a need to optimize the delivery of care
      such as self-management support. Digitalized solutions have the potential to
      modify and personalize the way in which people use primary health services, both
      by increasing access to information and providing other forms of support at a
      distance. It is a challenge to integrate core values of person-centered care into
      digitalized health care services. OBJECTIVE: The objective of this study was to
      describe perceptions of using electronic health (eHealth) services and related
      technologies for self-management support among people with T2D treated in Swedish
      primary health care. METHODS: This is a qualitative study based on interviews
      analyzed using qualitative content analysis conducted among people diagnosed with
      T2D. RESULTS: Findings suggest that the participants had mixed feelings regarding
      the use of digital health services for self-management support. They experienced
      potentials such as increased involvement, empowerment, and security, as well as
      concerns such as ambivalence and uncertainty. CONCLUSIONS: Digital health
      services for self-management are easily accessible and have the potential to
      reach a wide population. However, targeted training to increase digital skills is
      required, and personalized devices must be adapted and become more person
      centered to improve patients' involvement in their own care.

PMID- 30291076
TI  - Transitional Needs of Australian Young Adults With Type 1 Diabetes: Mixed Methods
      Study.
AB  - BACKGROUND: Young adulthood is marked by transitions that impact diabetes self
      management behaviors, which require ongoing diabetes education and support.
      Traditional diabetes education programs and services currently do not meet the
      needs of many young adults with type 1 diabetes mellitus (T1DM) as they continue
      to fall through the cracks of clinical services. Age-centered diabetes education
      programs and services present an opportunity for young adults to meet in a
      supportive environment and gain a better understanding about diabetes management.
      OBJECTIVE: The aim of the study was to identify the health and well-being needs
      of Australian young adults aged between 18 and 35 years with T1DM to develop
      appropriate solutions to keep them engaged with diabetes self-management.
      METHODS: In total, 13 semistructured individual interviews and self-reported
      surveys were obtained to understand participants' experiences with diabetes
      education programs and services. Together with survey data, transcribed
      interviews were analyzed into themes and categories using comparative analysis to
      identify the health and well-being needs of young adults with T1DM during young
      adulthood. RESULTS: Diabetes education and service needs for young adults with
      T1DM related to improving access to existing diabetes education programs and
      services, having credible informational resources, as well as having personalized
      diabetes management advice. Participants especially valued relevant and real-time
      information and opportunities for peer support, mostly sourced from Web-based
      platforms. CONCLUSIONS: There is a need for diabetes education programs and
      services to be age-appropriate and easily accessible, to provide relevant and
      credible information, and to provide opportunities for peer support to better
      support young adults with T1DM. These findings also support the use of diabetes
      education programs or services delivered online through mHealth systems in this
      population.

PMID- 30291077
TI  - An Interactive Simulation to Change Outcome Expectancies and Intentions in Adults
      With Type 2 Diabetes: Within-Subjects Experiment.
AB  - BACKGROUND: Computerized simulations are underutilized to educate or motivate
      patients with chronic disease. OBJECTIVE: The aim of this study was to test the
      efficacy of an interactive, personalized simulation that demonstrates the acute
      effect of physical activity on blood glucose. Our goal was to test its effects on
      physical activity-related outcome expectancies and behavioral intentions among
      adults with type 2 diabetes mellitus (T2DM). METHODS: In this within-subjects
      experiment, potential participants were emailed a link to the study website and
      directed through 7 tasks: (1) consent; (2) demographics, baseline intentions, and
      self-reported walking; (3) orientation to the diurnal glucose curve; (4) baseline
      outcome expectancy, measured by a novel drawing task in which participants use
      their mouse to draw the expected difference in the diurnal glucose curve if they
      had walked; (5) interactive simulation; (6) postsimulation outcome expectancy
      measured by a second drawing task; and (7) final measures of intentions and
      impressions of the website. To test our primary hypothesis that participants'
      outcome expectancies regarding walking would shift toward the outcome presented
      in the interactive simulation, we used a paired t test to compare the difference
      of differences between the change in area under the curve in the simulation and
      participants' two drawings. To test whether intentions to walk increased, we used
      paired t tests. To assess the intervention's usability, we collected both
      quantitative and qualitative data on participants' perceptions of the drawing
      tasks and simulation. RESULTS: A total of 2019 individuals visited the website
      and 1335 (566 males, 765 females, and 4 others) provided complete data.
      Participants were largely late middle-aged (mean=59.8 years; standard
      deviation=10.5), female 56.55% (755/1335), Caucasian 77.45% (1034/1335), lower
      income 64.04% (855/1335) t1334=3.4, P <=.001). Our second hypothesis, that
      participants' intentions to walk in the coming week would increase, was also
      supported; general intention (mean difference=0.31/7, t1001=10.8, P<.001) and
      minutes of walking last week versus planned for coming week (mean difference=33.5
      min, t1334=13.2, P<.001) both increased. Finally, an examination of qualitative
      feedback and drawing task data suggested that some participants had difficulty
      understanding the website. This led to a post-hoc subset analysis. In this
      analysis, effects for our hypothesis regarding outcome expectancies were markedly
      stronger, suggesting that further work is needed to determine moderators of the
      efficacy of this simulation. CONCLUSIONS: A novel interactive simulation is
      efficacious in changing the outcome expectancies and behavioral intentions of
      adults with T2DM. We discuss applications of our results to the design of mobile
      health (mHealth) interventions.

PMID- 30291078
TI  - Models Used in Clinical Decision Support Systems Supporting Healthcare
      Professionals Treating Chronic Wounds: Systematic Literature Review.
AB  - BACKGROUND: Chronic wounds such as diabetic foot ulcers, venous leg ulcers, and
      pressure ulcers are a massive burden to health care facilities. Many randomized
      controlled trials on different wound care elements have been conducted and
      published in the Cochrane Library, all of which have only a low evidential basis.
      Thus, health care professionals are forced to rely on their own experience when
      making decisions regarding wound care. To progress from experience-based practice
      to evidence-based wound care practice, clinical decision support systems (CDSS)
      that help health care providers with decision-making in a clinical workflow have
      been developed. These systems have proven useful in many areas of the health care
      sector, partly because they have increased the quality of care, and partially
      because they have generated a solid basis for evidence-based practice. However,
      no systematic reviews focus on CDSS within the field of wound care to chronic
      wounds. OBJECTIVE: The aims of this systematic literature review are (1) to
      identify models used in CDSS that support health care professionals treating
      chronic wounds, and (2) to classify each clinical decision support model
      according to selected variables and to create an overview. METHODS: A systematic
      review was conducted using 6 databases. This systematic literature review follows
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement
      for systematic reviews. The search strategy consisted of three facets,
      respectively: Facet 1 (Algorithm), Facet 2 (Wound care) and Facet 3 (Clinical
      decision support system). Studies based on acute wounds or trauma were excluded.
      Similarly, studies that presented guidelines, protocols and instructions were
      excluded, since they do not require progression along an active chain of
      reasoning from the clinicians, just their focus. Finally, studies were excluded
      if they had not undergone a peer review process. The following aspects were
      extracted from each article: authors, year, country, the sample size of data and
      variables describing the type of clinical decision support models. The decision
      support models were classified in 2 ways: quantitative decision support models,
      and qualitative decision support models. RESULTS: The final number of studies
      included in the systematic literature review was 10. These clinical decision
      support models included 4/10 (40%) quantitative decision support models and 6/10
      (60%) qualitative decision support models. The earliest article was published in
      2007, and the most recent was from 2015. CONCLUSIONS: The clinical decision
      support models were targeted at a variety of different types of chronic wounds.
      The degree of accessibility of the inference engines varied. Quantitative models
      served as the engine and were invisible to the health care professionals, while
      qualitative models required interaction with the user.

PMID- 30291079
TI  - Effect of Diabetes Online Community Engagement on Health Indicators: Cross
      Sectional Study.
AB  - BACKGROUND: Successful diabetes management requires ongoing lifelong self-care
      and can require that individuals with diabetes become experts in translating care
      recommendations into real-life day-to-day diabetes self-care strategies. The
      diabetes online community comprises multiple websites that include social media
      sites, blogs, and discussion groups for people with diabetes to chat and exchange
      information. Online communities can provide disease-specific practical advice and
      emotional support, allow users to share experiences, and encourage self-advocacy
      and patient empowerment. However, there has been little research about whether
      diabetes online community use is associated with better diabetes self-care or
      quality of life. OBJECTIVE: The aim of this study was to survey adults with
      diabetes who participated in the diabetes online community to better understand
      and describe who is using the diabetes online community, how they are using it,
      and whether the use of the diabetes online community was associated with health
      indicators. METHODS: We recruited adults diagnosed with diabetes who used at
      least one of 4 different diabetes-related online communities to complete an
      online survey. Participants' demographics, reported glycated hemoglobin (HbA1c),
      health-related quality of life (SF-12v2), level of diabetes self-care (Self-Care
      Inventory-Revised), and diabetes online community use (level of intensity and
      engagement) were collected. We examined the relationships between demographics,
      diabetes online community use, and health indicators (health-related quality of
      life, self-care, and HbA1c levels). We used binary logistic regression to
      determine the extent to which diabetes online community use predicted an HbA1c
      <7% or >=7% after controlling statistically for other variables in the model.
      RESULTS: A total of 183 adults participated in this study. Participants were
      mostly female (71.6%, 131/183), white (95.1%, 174/183), US citizens (82.5%,
      151/183), had type 1 diabetes (69.7%, 129/183), with a mean age of 44.7 years (SD
      14) and diabetes duration of 18.2 years (SD 14.6). Participants had higher
      diabetes self-care (P<.001, mean 72.4, SD 12.1) and better health-related quality
      of life (physical component summary P<.001, mean 64.8, SD 19; mental component
      summary P<.001, mean 66.6, SD 21.6) when compared with norms for diabetes.
      Diabetes online community engagement was a strong predictor of A1c, reducing the
      odds of having an A1c >=7% by 33.8% for every point increase in diabetes online
      community engagement (0-5). Our data also indicated that study participants are
      oftentimes (67.2%, 123/183) not informing their healthcare providers about their
      diabetes online community use even though most (91.2%, 161/181) are seeing their
      healthcare provider on a regular basis. CONCLUSIONS: Our results suggest that
      individuals highly engaged with diabetes online community are more likely to have
      better glycemic levels compared with those with lower engagement. Furthermore,
      diabetes online community users have high health-related quality of life and
      diabetes self-care levels. Supplementing usual healthcare activities with
      diabetes online community use may encourage knowledge and support among a
      population that needs to optimize its diabetes self-care. Further studies are
      needed to determine how diabetes online community engagement may affect health
      outcomes.

PMID- 30291080
TI  - The Case for Jointly Targeting Diabetes and Depression Among Vulnerable Patients
      Using Digital Technology.
AB  - It is well publicized that mobile and digital technologies hold great promise to
      improve health outcomes among patients with chronic illnesses such as diabetes.
      However, there is growing concern that digital health investments (both from
      federal research dollars and private venture investments) have not yet resulted
      in tangible health improvements. We see three major reasons for this limited real
      world impact on health outcomes: (1) lack of solutions relevant for patients with
      multiple comorbidities or conditions, (2) lack of diverse patient populations
      involved in the design and early testing of products, and (3) inability to
      leverage existing clinical workflows to improve both patient enrollment and
      engagement in technology use. We discuss each of these in depth, followed by new
      research directions to increase effectiveness in this field.

PMID- 30291081
TI  - Outcomes of a Digitally Delivered Low-Carbohydrate Type 2 Diabetes Self
      Management Program: 1-Year Results of a Single-Arm Longitudinal Study.
AB  - BACKGROUND: Type 2 diabetes mellitus has serious health consequences, including
      blindness, amputation, stroke, and dementia, and its annual global costs are more
      than US $800 billion. Although typically considered a progressive, nonreversible
      disease, some researchers and clinicians now argue that type 2 diabetes may be
      effectively treated with a carbohydrate-reduced diet. OBJECTIVE: Our objective
      was to evaluate the 1-year outcomes of the digitally delivered Low-Carb Program,
      a nutritionally focused, 10-session educational intervention for glycemic control
      and weight loss for adults with type 2 diabetes. The program reinforces
      carbohydrate restriction using behavioral techniques including goal setting, peer
      support, and behavioral self-monitoring. METHODS: The study used a quasi
      experimental research design comprised of an open-label, single-arm, pre-post
      intervention using a sample of convenience. From adults with type 2 diabetes who
      had joined the program and had a complete baseline dataset, we randomly selected
      participants to be followed for 1 year (N=1000; mean age 56.1, SD 15.7 years;
      59.30% (593/1000) women; mean glycated hemoglobin A1c (HbA1c) 7.8%, SD 2.1%; mean
      body weight 89.6 kg, SD 23.1 kg; taking mean 1.2, SD 1.01 diabetes medications).
      RESULTS: Of the 1000 study participants, 708 (70.80%) individuals reported
      outcomes at 12 months, 672 (67.20%) completed at least 40% of the lessons, and
      528 (52.80%) completed all lessons of the program. Of the 743 participants with a
      starting HbA1c at or above the type 2 diabetes threshold of 6.5%, 195 (26.2%)
      reduced their HbA1c to below the threshold while taking no glucose-lowering
      medications or just metformin. Of the participants who were taking at least one
      hypoglycemic medication at baseline, 40.4% (289/714) reduced one or more of these
      medications. Almost half (46.40%, 464/1000) of all participants lost at least 5%
      of their body weight. Overall, glycemic control and weight loss improved,
      especially for participants who completed all 10 modules of the program. For
      example, participants with elevated baseline HbA1c (>=7.5%) who engaged with all
      10 weekly modules reduced their HbA1c from 9.2% to 7.1% (P<.001) and lost an
      average of 6.9% of their body weight (P<.001). CONCLUSIONS: Especially for
      participants who fully engage, an online program that teaches a carbohydrate
      reduced diet to adults with type 2 diabetes can be effective for glycemic
      control, weight loss, and reducing hypoglycemic medications.

PMID- 30291082
TI  - Web-Based Interventions for Depression in Individuals with Diabetes: Review and
      Discussion.
AB  - BACKGROUND: Depression is twice as common in people with diabetes, and this
      comorbidity worsens the course of both pathologies. In clinical practice
      guidelines, screening and treatment of depression in patients with diabetes are
      highly recommended. However, depression is still both underrecognized and
      undertreated. To find ways to enhance their reach, psychological treatments have
      taken advantage of benefits of internet and technological devices as delivery
      formats, providing interventions that require considerably less (or even no)
      interaction time with therapists. Web-based treatments hold promise for effective
      interventions at low cost with positive results. OBJECTIVE: The objectives of
      this review were to describe Web-based interventions for depression in
      individuals with diabetes and to discuss these studies' procedures and findings
      in light of evidence from a wider range of interventions for depression and
      diabetes. METHODS: A comprehensive literature search was conducted in PsycINFO
      and MEDLINE electronic databases. Studies were included when they met the
      following selection criteria: the study was available in a peer-reviewed journal
      mainly publishing studies written in either English or Spanish; the studied
      sample comprised individuals with diabetes; the intervention targeted depression
      symptomatology; the intervention was accessible via the internet; and the
      intervention was accessible via the internet with little or no clinician support.
      RESULTS: Overall, 5 research studies were identified in the review. All studies
      were randomized controlled trials, and most used a wait list as a control; 4
      studies reported treatment dropout, rates of which varied from 13% to 42%.
      Studies supported the notion that the Web-based format is a suitable psychology
      service delivery option for diabetic individuals with depression (effect size
      range for completers 0.7-0.89). Interventions varied in their characteristics but
      most were clinical-assisted, had a cognitive behavioral therapy approach, used
      diabetes-specific topics, had a weekly modular display, used homework
      assignments, and had some adherence management strategy. These characteristics
      are consistent with the intervention features associated with positive results in
      the literature. CONCLUSIONS: The analyzed studies' findings and procedures are
      discussed in light of evidence drawn from a wider range of reviews on Web-based
      interventions for depression and diabetes. Consistent with previous research on
      depression treatment, Web-based interventions for depression among individuals
      with diabetes have shown positive results. Future research should contribute new
      evidence as to why these interventions are effective, for whom, and which
      particular aspects can increase patients' adherence.

PMID- 30291083
TI  - Information and Communication Technology-Powered Diabetes Self-Management Systems
      in China: A Study Evaluating the Features and Requirements of Apps and Patents.
AB  - BACKGROUND: For patients with diabetes, the self-monitoring of blood glucose
      (SMBG) is a recommended way of controlling the blood glucose level. By leveraging
      the modern information and communication technology (ICT) and the corresponding
      infrastructure, engineers nowadays are able to merge the SMBG activities into
      daily life and to dramatically reduce patient's burden. Such type of ICT-powered
      SMBG had already been marketed in the United States and the European Union for a
      decade, but was introduced into the Chinese market only in recent years. Although
      there is no doubt about the general need for such type of SMBG in the Chinese
      market, how it could be adapted to the local technical and operational
      environment is still an open question. OBJECTIVE: Our overall goal is to
      understand the local requirements and the current status of deploying ICT-powered
      SMBG to the Chinese market. In particular, we aim to analyze existing domestic
      SMBG mobile apps and relevant domestic patents to identify their various aspects,
      including the common functionalities, innovative feature, defects, conformance to
      standards, prospects, etc. In the long run, we hope the outcome of this study
      could help the decision making on how to properly adapt ICT-powered SMBG to the
      Chinese market. METHODS: We identified 289 apps. After exclusion of irrelevant
      apps, 78 apps remained. These were downloaded and analyzed. A total of 8070
      patents related to glucose were identified from patent database. Irrelevant
      materials and duplicates were excluded, following which 39 patents were parsed to
      extract the important features. These apps and patents were further compared with
      the corresponding requirements derived from relevant clinical guidelines and data
      standards. RESULTS: The most common features of studied apps were blood health
      data recording, notification, and decision supporting. The most common features
      of studied patents included mobile terminal, server, and decision supporting. The
      main difference between patents and apps is that the patents had 2 specific
      features, namely, interface to the hospital information system and recording
      personal information, which were not mentioned in the app. The other major
      finding is that, in general, in terms of the components of the features, although
      the features identified in both apps and patents conform to the requirements of
      the relevant clinical guidelines and data standards, upon looking into the
      details, gaps exist between the features of the identified apps and patents and
      the relevant clinical guidelines and data standards. In addition, the social
      media feature that the apps and patents have is not included in the standard
      requirements list. CONCLUSIONS: The development of Chinese SMBG mobile apps and
      relevant patents is still in the primitive stage. Although the functionalities of
      most apps and patents can meet the basic requirements of SMBG, gaps have been
      identified when comparing the functionalities provided by apps and patents with
      the requirements necessitated by the standards. One of the most important gaps is
      that only a small portion of the studied apps provides the automatic data
      transmission and exchange feature, which may hamper the overall performance. The
      clinical guidelines can thus be further developed to leverage new features
      provided by ICT-powered SMBG apps (eg, the social media feature, which may help
      to improve the social intervention of patients with diabetes).

PMID- 30291084
TI  - Machine or Human? Evaluating the Quality of a Language Translation Mobile App for
      Diabetes Education Material.
AB  - BACKGROUND: Diabetes is a major health crisis for Hispanics and Asian Americans.
      Moreover, Spanish and Chinese speakers are more likely to have limited English
      proficiency in the United States. One potential tool for facilitating language
      communication between diabetes patients and health care providers is technology,
      specifically mobile phones. OBJECTIVE: Previous studies have assessed machine
      translation quality using only writing inputs. To bridge such a research gap, we
      conducted a pilot study to evaluate the quality of a mobile language translation
      app (iTranslate) with a voice recognition feature for translating diabetes
      patient education material. METHODS: The pamphlet, "You are the heart of your
      family...take care of it," is a health education sheet for diabetes patients that
      outlines three recommended questions for patients to ask their clinicians. Two
      professional translators translated the original English sentences into Spanish
      and Chinese. We recruited six certified medical translators (three Spanish and
      three Chinese) to conduct blinded evaluations of the following versions: (1)
      sentences interpreted by iTranslate, and (2) sentences interpreted by the
      professional human translators. Evaluators rated the sentences (ranging from 1-5)
      on four scales: Fluency, Adequacy, Meaning, and Severity. We performed
      descriptive analyses to examine the differences between these two versions.
      RESULTS: Cronbach alpha values exhibited high degrees of agreement on the rating
      outcomes of both evaluator groups: .920 for the Spanish raters and .971 for the
      Chinese raters. The readability scores generated using MS Word's Flesch-Kincaid
      Grade Level for these sentences were 0.0, 1.0, and 7.1. We found iTranslate
      generally provided translation accuracy comparable to human translators on simple
      sentences. However, iTranslate made more errors when translating difficult
      sentences. CONCLUSIONS: Although the evidence from our study supports
      iTranslate's potential for supplementing professional human translators, further
      evidence is needed. For this reason, mobile language translation apps should be
      used with caution.

PMID- 30291085
TI  - Use of a Mobile App to Facilitate Blood Glucose Monitoring in Adolescents With
      Type 1 Diabetes: Single-Subject Nonrandomized Clinical Trial.
AB  - BACKGROUND: Cloud-based glucose monitoring programs allow users with diabetes to
      wirelessly synchronize their glucometers to their mobile phones. They also
      provide visualization and remote access of their data through its mobile app.
      There have been very few studies evaluating their effectiveness in managing
      diabetes among adolescents with type 1 diabetes (T1D). OBJECTIVE: The purpose of
      this study was to assess the feasibility of using a mobile app to improve daily
      average blood glucose (BG) levels and increase BG monitoring frequency. METHODS:
      We used an ABA single-subject prospective study design. We recruited five
      participants aged 13 to 17 years with uncontrolled T1D, glycated hemoglobin A1c
      9.0%-10.7%, self-monitoring behavior of <=5 checks/day, and on multiple daily
      insulin injections. The study consisted of 4-week intervals of three phases: (1)
      phase A: usual glucose monitoring log (fax); (2) phase B: mobile app; and (3)
      phase A': second phase A. A certified diabetes educator and endocrinologist
      reviewed logs and provided recommendations weekly. Data were analyzed using a
      quasi-Poisson model to adjust for overdispersion among individual participants,
      and a generalized estimating equation model for overall intervention effect in
      aggregate. RESULTS: For mean daily BG (mg/dL) levels, participant 1 had decreased
      values on the mobile app (298 to 281, P=.03) and maintained in phase A'.
      Participant 4 had an increase in mean daily BG in phase A' (175 to 185, P=.01),
      whereas participant 5 had a decrease in mean daily BG in phase A' (314 to 211,
      P=.04). For daily monitoring (checks/day), participant 3 increased in phase B
      (4.6 to 8.3, P=.01) and maintained in phase A'. Participant 5 also had increased
      daily monitoring at each phase (2.1 to 2.4, P=.01; 2.4 to 3.4, P=.02). For the
      five participants combined, the overall mean BG and BG checks per day in phase A
      were mean 254.8 (SD 99.2) and mean 3.6 (SD 2.0), respectively, mean 223.1 (SD
      95.7) and mean 4.5 (SD 3.0) in phase B, and mean 197.5 (SD 81.3) and mean 3.7 (SD
      2.1) in phase A'. Compared to phase A, mean glucose levels declined during phase
      B and remained lower during phase A' (P=.002). There was no overall change in BG
      checks by phase (P=.25). However, mean BG levels negatively correlated with daily
      BG checks (r=-.47, P<.001). Although all participants had positive opinions about
      the app, its utilization was highly variable. CONCLUSIONS: We demonstrated modest
      feasibility of adolescents with uncontrolled T1D utilizing a glucose monitoring
      mobile app. Further study is needed to better determine its effects on BG level
      and monitoring frequency. Psychosocial factors and motivational barriers likely
      influence adoption and continuous use of technology for diabetes management.

PMID- 30291086
TI  - Exploring the Use of Personal Technology in Type 2 Diabetes Management Among
      Ethnic Minority Patients: Cross-Sectional Analysis of Survey Data from the
      Lifestyle Intervention for the Treatment of Diabetes Study (LIFT Diabetes).
AB  - BACKGROUND: Minority populations have higher morbidity from chronic diseases and
      typically experience worse health outcomes. Internet technology may afford a low
      cost method of ongoing chronic disease management to promote improved health
      outcomes among minority populations. OBJECTIVE: The objective of our study was to
      assess the feasibility of capitalizing on the pervasive use of technology as a
      secondary means of delivering diabetic counseling though an investigation of
      correlates to technology use within the context of an ongoing diabetes
      intervention study. METHODS: The Lifestyle Intervention for the Treatment of
      Diabetes study (LIFT Diabetes) randomly assigned 260 overweight and obese adults
      with type 2 diabetes mellitus to 2 intervention arms. At baseline, we
      administered a survey evaluating access to and use of various technologies and
      analyzed the responses using descriptive statistics and logistic regression.
      RESULTS: The sample population had a mean age of 56 (SD 11) years; 67.3%
      (175/260) were female and 54.6% (n=142) self-identified as being from ethnic
      minority groups (n=125, 88.0% black; n=6, 4.3% Hispanic; and n=11, 7.7% other).
      Minority participants had higher baseline mean body mass index (P=.002) and
      hemoglobin A1c levels (P=.003). Minority participants were less likely to have a
      home computer (106/142, 74.7% vs 110/118, 93.2%; P<.001) and less likely to have
      email access at home (P=.03). Ownership of a home computer was correlated to
      higher income (P<.001), higher educational attainment (P<.001), full-time
      employment (P=.01), and ownership of a smartphone (P=.001). Willingness to
      complete questionnaires online was correlated to higher income (P=.001), higher
      education (P<.001), full-time employment (P=.01), and home access to a computer,
      internet, and smartphone (P<=.05). Racial disparities in having a home computer
      persisted after controlling for demographic variables and owning a smartphone
      (adjusted OR 0.26, 95% CI 0.10-0.67; P=.01). Willingness to complete
      questionnaires online was driven by ownership of a home computer (adjusted OR
      3.87, 95% CI 1.14-13.2; P=.03). CONCLUSIONS: Adults who self-identified as being
      part of a minority group were more likely to report limited access to technology
      than were white adults. As ownership of a home computer is central to a
      willingness to use online tools, racial disparities in access may limit the
      potential of Web-based interventions to reach this population. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01806727;
      https://clinicaltrials.gov/ct2/show/NCT01806727 (Archived by WebCite at
      http://www.webcitation.org/6xOq2b7Tv).

PMID- 30291087
TI  - A Fully Automated Conversational Artificial Intelligence for Weight Loss:
      Longitudinal Observational Study Among Overweight and Obese Adults.
AB  - BACKGROUND: Type 2 diabetes is the most expensive chronic disease in the United
      States. Two-thirds of US adults have prediabetes or are overweight and at risk
      for type 2 diabetes. Intensive in-person behavioral counseling can help patients
      lose weight and make healthy behavior changes to improve their health outcomes.
      However, with the shortage of health care providers and associated costs, such
      programs do not adequately service all patients who could benefit. The health
      care system needs effective and cost-effective interventions that can lead to
      positive health outcomes as scale. This study investigated the ability of
      conversational artificial intelligence (AI), in the form of a standalone, fully
      automated text-based mobile coaching service, to promote weight loss and other
      health behaviors related to diabetes prevention. This study also measured user
      acceptability of AI coaches as alternatives to live health care professionals.
      OBJECTIVE: The objective of this study was to evaluate weight loss, changes in
      meal quality, and app acceptability among users of the Lark Weight Loss Health
      Coach AI (HCAI), with the overarching goal of increasing access to compassionate
      health care via mobile health. Lessons learned in this study can be applied when
      planning future clinical trials to evaluate HCAI and when designing AI to promote
      weight loss, healthy behavior change, and prevention and self-management of
      chronic diseases. METHODS: This was a longitudinal observational study among
      overweight and obese (body mass index >=25) participants who used HCAI, which
      encourages weight loss and healthy diet choices through elements of cognitive
      behavioral therapy. Weight loss, meal quality, physical activity, and sleep data
      were collected through user input and, for sleep and physical activity, partly
      through automatic detection by the user's mobile phone. User engagement was
      assessed by duration and amount of app use. A 4-question in-app user trust survey
      assessed app usability and acceptability. RESULTS: Data were analyzed for
      participants (N=70) who met engagement standards set forth by the Centers for
      Disease Control and Prevention criteria for Diabetes Prevention Program, a
      clinically proven weight loss program focused on preventing diabetes. Weight loss
      (standard error of the mean) was 2.38% (0.69%) of baseline weight. The average
      duration of app use was 15 (SD 1.0) weeks, and users averaged 103 sessions each.
      Predictors of weight loss included duration of AI use, number of counseling
      sessions, and number of meals logged. Percentage of healthy meals increased by
      31%. The in-app user trust survey had a 100% response rate and positive results,
      with a satisfaction score of 87 out of 100 and net promoter score of 47.
      CONCLUSIONS: This study showed that use of an AI health coach is associated with
      weight loss comparable to in-person lifestyle interventions. It can also
      encourage behavior changes and have high user acceptability. Research into AI and
      its application in telemedicine should be pursued, with clinical trials
      investigating effects on weight, health behaviors, and user engagement and
      acceptability.

PMID- 30291088
TI  - Functionality, Implementation, Impact, and the Role of Health Literacy in Mobile
      Phone Apps for Gestational Diabetes: Scoping Review.
AB  - BACKGROUND: The increasing ownership of mobile phones and advances in hardware
      and software position these devices as cost-effective personalized tools for
      health promotion and management among women with gestational diabetes mellitus
      (GDM). Numerous mobile phone apps are available online; however, to our
      knowledge, no review has documented how these apps are developed and evaluated in
      relation to GDM. OBJECTIVE: The objective of our review was to answer the
      following 2 research questions: (1) What is known from the existing literature
      about the availability, functionality, and effectiveness of mobile phone apps on
      GDM prevention and management? (2) What is the role of health literacy in these
      apps? METHODS: We searched 7 relevant electronic databases for original research
      documents using terms related to mobile phone apps, GDM, and health literacy. We
      thematically categorized selected articles using a framework adapted from Arksey
      and O'Malley. RESULTS: We included 12 articles related to 7 apps or systems in
      the final analysis. We classified articles around 2 themes: (1) description of
      the development, feasibility, or usability of the apps or systems, and (2) trial
      protocols. The degree of personalization varied among the apps for GDM, and
      decision support systems can be used to generate time-efficient personalized
      feedback for both patients and health care providers. Health literacy was
      considered during the development or measured as an outcome by some apps.
      CONCLUSIONS: There is a limited body of research on mobile phone apps in relation
      to GDM prevention and management. Mobile phone apps can provide time- and cost
      efficient personalized interventions for GDM. Several randomized controlled
      trials have been launched recently to evaluate the effectiveness of the apps.
      Consideration of health literacy should be improved when developing features of
      the apps.

PMID- 30291089
TI  - Views of Patients on Using mHealth to Monitor and Prevent Diabetic Foot Ulcers:
      Qualitative Study.
AB  - BACKGROUND: People with diabetes are at risk for diabetic foot ulcers (DFUs),
      which can lead to limb loss and a significant decrease in quality of life.
      Evidence suggests that mHealth can be an effective tool in diabetes self
      management. mHealth presents an opportunity for the prevention and monitoring of
      DFUs. However, there is a paucity of research that explores its effectiveness in
      the DFU patient population, as well as the views and attitudes of these patients
      toward technology and mHealth. OBJECTIVE: This study aimed to explore the views,
      attitudes, and experiences of a diabetic patient population with or at risk of
      DFUs regarding technology, mHealth, and the diabetic foot. METHODS: We used a
      qualitative research approach using in-depth interviews with 8 patients with
      DFUs. Questions were structured around experience with technology, current health
      practices related to diabetic foot care, and thoughts on using an mHealth device
      that prevents and monitors DFUs. We transcribed and thematically analyzed all
      interviews. RESULTS: All patients had positive responses for an mHealth
      intervention aimed at preventing and monitoring DFUs. We found 4 themes in the
      data: diversity in use of technology, feet-checking habits, 2-way communication
      with health care professionals (HCPs), and functionality. There were varying
      levels of familiarity with and dependence on technology within this patient
      population. These relationships correlated with distinct generations found in
      North America, including baby boomers and Generation X. Furthermore, we found
      that most patients performed daily feet checks to monitor any changes in health.
      However, some did not perform feet checks prior to the development of a DFU.
      Patients expressed interest in 2-way communication with HCPs that would allow for
      easier appointment scheduling, sharing of medical data, decreased number of
      visits, and use of alerts for when medical attention is required. Patients also
      identified conditions of functionality for the mHealth intervention. These
      included consideration of debilitating complications because of diabetes, such as
      retinopathy and decreased mobility; ease of use of the intervention; and
      implementation of virtual communities to support continued use of the
      intervention. CONCLUSIONS: Our patient population expressed an interest in
      mHealth for preventing and monitoring DFUs, although some participants were not
      frequent users of technology. mHealth continues to show potential in improving
      patient outcomes, and this study provides a foundation for designing
      interventions specific to a DFU population. Further research is needed to confirm
      these findings.

PMID- 30291090
TI  - Addressing Disparities in Diabetes Management Through Novel Approaches to
      Encourage Technology Adoption and Use.
AB  - Type 2 diabetes (T2D) is one of the nation's leading drivers of disability and
      health care utilization, with elevated prevalence among individuals with lower
      education, income, and racial/ethnic minorities. Health information technology
      (HIT) holds vast potential for helping patients, providers, and payers to address
      T2D and the skyrocketing rates of chronic illness and associated health care
      costs. Patient portals to electronic health records (EHRs) serve as a gateway to
      consumer use of HIT. We found that disparities in portal use portend growing T2D
      disparities. Little progress has been made in addressing identified barriers to
      technology adoption, especially among populations with elevated risk of T2D.
      Patients often lack digital literacy skills and continuous connectivity and fear
      loss of the relationship with providers. Providers may experience structural
      disincentives to promoting patient use of HIT and apply hidden biases that
      inhibit portal use. Health care systems often provide inadequate training to
      patients and providers in use of HIT, and lack resources devoted to obtaining and
      optimizing use of data generated by HIT. Lastly, technology-related barriers
      include inadequate consideration of user perspectives, lack of evidence for
      patient-focused apps, and lack of features to enable providers and health care
      systems to readily obtain aggregate data to improve care and facilitate research.
      After discussing these barriers in detail, we propose possible solutions and
      areas where further research is needed to ensure that individuals and health care
      systems obtain the full benefit of the nation's planned $38 billion HIT
      investment. A digital inclusion framework sheds new light on barriers posed for
      patients with social health inequalities. We have determined that partnerships
      with community organizations focused on digital inclusion could help health
      systems explore and study new approaches, such as universal screening and
      referral of patients for digital skills, health literacy, and Internet
      connectivity.

PMID- 30291091
TI  - A Website to Promote Physical Activity in People With Type 2 Diabetes Living in
      Remote or Rural Locations: Feasibility Pilot Randomized Controlled Trial.
AB  - BACKGROUND: Research supports the use of Web-based interventions to promote
      physical activity in diabetes management. However, previous interventions have
      found poor levels of engagement or have not included health professionals and
      people with diabetes in the design of the tool. OBJECTIVE: To develop and explore
      the feasibility and indicative effect of a Web-based physical activity promotion
      intervention in people diagnosed with type 2 diabetes living in remote or rural
      locations. METHODS: A qualitative approach using focus groups that included
      patients with diabetes and health professionals were run to identify key
      concepts, ideas, and features, which resulted in the design of a physical
      activity website. This site was tested using a quantitative approach with a
      qualitative 6-month pilot study that adopted a three-armed approach. Participants
      were randomized into three groups: a control group who received written diabetes
      specific physical activity advice; an information Web group, a Web-based group
      who received the information online; and an intervention Web group, an
      interactive Web-based group who received online information plus interactive
      features, such as an activity log, personalized advice, and goal setting.
      RESULTS: A website was designed based on patient and health professional ideas
      for effective physical activity promotion. This website was tested with 31
      participants, 61% (19/31) male, who were randomized into the groups. Website log
      ins decreased over time: 4.5 times in month 1, falling to 3 times in month 6.
      Both the information Web group-mean 134.6 (SD 123.9) to mean 154.9 (SD 144.2) min
      and the control group-mean 118.9 (SD 103.8) to mean 126.1 (SD 93.4) min, d=0.07
      increased time spent in moderate-to-vigorous physical activity, but this
      decreased in the intervention Web group-mean 131.9 (SD 126.2) to mean 116.8 (SD
      107.4) min. CONCLUSIONS: Access to online diabetes-specific physical information
      was effective in promoting physical activity in people with type 2 diabetes;
      access to interactive features was not associated with increases in activity.
      TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number
      (ISRCTN): 96266587; http://www.isrctn.com/ISRCTN96266587 (Archived by WebCite at
      http://www.webcitation.org/6tzX6YesZ).

PMID- 30291092
TI  - Diabetes App-Related Text Messages From Health Care Professionals in Conjunction
      With a New Wireless Glucose Meter With a Color Range Indicator Improves Glycemic
      Control in Patients With Type 1 and Type 2 Diabetes: Randomized Controlled Trial.
AB  - BACKGROUND: Mobile diabetes apps enable health care professionals (HCPs) to
      monitor patient progress, offer remote consultations, and allow more effective
      and informed treatment decisions between patients and HCPs. The OneTouch Reveal
      app aggregates data from a blood glucose meter and provides analytics to help
      patients and HCPs visualize glycemic trends and patterns, enabling more informed
      treatment and lifestyle decisions. The app also allows patients and HCPs to keep
      connected by exchanging text messages (short message service [SMS]) or progress
      reports via email. OBJECTIVE: The primary objective of our study was to assess
      changes in glycemic control and overall experiences of patients and HCPs using
      the app in conjunction with the wireless OneTouch Verio Flex blood glucose meter.
      METHODS: We randomly assigned 137 adults with type 1 (T1DM) or type 2 diabetes
      mellitus (T2DM) and a glycated hemoglobin (HbA1c) level of >=7.5% and <=11.0% to
      use the glucose meter alone or glucose meter plus the app for 24 weeks. The meter
      + app group were scheduled to receive diabetes-related text messages from their
      HCP every 2 weeks (total of 12 texts). Clinical measures and self-reported
      outcomes were assessed during face-to-face clinic visits between the participant
      and a diabetes nurse at baseline, week 12, and week 24. RESULTS: In 128 completed
      participants, HbA1c decreased after 12 and 24 weeks in both the meter-only (n=66)
      (0.56% and 0.55%, respectively) and meter + app groups (n=62) (0.78% and 0.67%,
      respectively) compared with baseline (each P<.001). The difference in HbA1c
      reduction between the 2 groups was not statistically significant at 12 or 24
      weeks (P=.12 and P=.45, respectively). However, the decrease in HbA1c was greater
      in T2DM participants using the meter + app after 12 weeks (1.04%) than in T2DM
      participants using the meter alone (0.58%; P=.09). In addition, decrease in HbA1c
      in participants using the meter + app who received at least 10 diabetes-related
      text messages (1.05%) was significantly greater than in meter-only participants
      (P<.01). CONCLUSIONS: Use of the OneTouch Verio Flex glucose meter alone or in
      combination with the OneTouch Reveal diabetes app was associated with significant
      improvements in glycemic control after 12 and 24 weeks. Improvements using the
      app were greatest in participants with T2DM and those participants who received
      the highest number of HCP text messages. This study suggests that real-time
      availability of patient data and the ability to send personalized diabetes
      related text messages can assist HCPs to improve glycemic control in patients
      between scheduled visits. TRIAL REGISTRATION: Clinicaltrials.gov NCT02429024;
      https://clinicaltrials.gov/ct2/show/NCT02429024 (Archived by WebCite at
      http://www.webcitation.org/6sCTDRa1l).

PMID- 30291093
TI  - Digital Health for Medication Adherence in Adult Diabetes or Hypertension: An
      Integrative Review.
AB  - BACKGROUND: Optimal management of chronic diseases, such as type 2 diabetes and
      hypertension, often include prescription medications. Medication adherence (MA)
      is one component of self-management. Optimization through digital health-eHealth
      and mHealth-could enhance patient awareness and/or communication between the
      patient and provider. OBJECTIVE: Medication adherence is a major issue that
      affects 50%-60% of chronically ill adults. Digital health refers to eHealth and
      mHealth, collectively, and as these technologies become more accessible, remote
      health delivery is increasingly available as an adjunct to improve medication
      adherence; communicate with patients and providers; and provide education to
      patients, families, and communities. The objective of this integrative review was
      to examine the types of digital health technologies that targeted medication
      adherence in the adult population with diabetes or hypertension. METHODS: An
      integrative review was conducted using databases within EBSCOhost, PubMed, and
      Scopus. Eligible studies available as of September 2016 had to be written in
      English, had to contain digital health interventions to improve medication
      adherence to prescription medications in adults 18 years or older, and had to
      focus on diabetes or hypertension. RESULTS: Of the 337 located studies, 13 (3.9%)
      used a digital health intervention for medication adherence to prescribed
      medications for diabetes or hypertension and were assessed according to the
      Chronic Care Model. CONCLUSIONS: The 13 studies included in this review found no
      conclusive evidence of improved medication adherence using digital health
      interventions such as interactive voice response (IVR), short message service
      (SMS) text messaging, telemonitoring, and interactive software technology. Among
      the 13 studies were digital health interventions that foster medication adherence
      via one-way communication to the patient or two-way communication between the
      patient and health care provider for adjunct medication adherence strategies.
      More research is needed to determine which digital health interventions are most
      beneficial for individuals with diabetes or hypertension.

PMID- 30291094
TI  - Phone Messaging to Prompt Physical Activity and Social Support Among Low-Income
      Latino Patients With Type 2 Diabetes: A Randomized Pilot Study.
AB  - BACKGROUND: Given disparities in diabetes prevalence, receipt of diabetes
      education, diabetes knowledge, and self-management behaviors among Latinos, there
      is a need to provide education and ongoing support to this population. Phone
      based interventions have the potential to reach and engage both patients and
      their family members and friends. OBJECTIVE: The aim of this study was to
      investigate the feasibility, perceived usefulness, and potential effectiveness of
      a short text or voice message (STVM) intervention to activate (1) physical
      activity (PA) behavior change among urban, low-income Latino adults with type 2
      diabetes and (2) supportive behaviors by their family members and friends.
      METHODS: A 12-week pilot study randomized 42 participants recruited in person
      from a safety-net ambulatory care clinic in Los Angeles into one of the 3 study
      arms: control, phone messaging (PM), and phone messaging plus social support from
      family members and friends (PM+FF). All participants were prompted to set PA
      goals and to self-monitor PA behavior using pedometers and walking logs. PM and
      PM+FF participants received STVMs with reminders to review goals and self
      monitor, PA behavior change education, and feedback on performance. Participants
      in the PM+FF arm also had their family members and friends receiving STVMs with
      suggestions for how they could support the participant's PA behavior change
      efforts. Participants completed semistructured assessments in person at baseline,
      6 weeks, and 12 weeks. Outcomes were PA (steps/day) and perceived social support
      from family members and friends. RESULTS: Among PM and PM+FF participants, those
      who opted to receive text messages (short message service, SMS) responded to
      62.7% (128/204) of SMS text messages requiring a response while those who opted
      to receive voice messages responded 30% (12/40) of the time. Participants
      perceived guidance in self-regulation as useful, particularly self-monitoring,
      goal setting, self-instruction, feedback, and social support. All participants
      increased PA at 6 weeks, but only the PM and PM+FF arms increased PA at 12 weeks.
      All study arms experienced an increase in perceived social support from family
      members and friends at 6 weeks, but only those in the PM+FF arm had an increase
      in the perception of social support at 12 weeks. CONCLUSION: Designing an STVM
      intervention based on self-regulation techniques is feasible and perceived as
      useful by participants. The STVM intervention has the potential to improve PA in
      terms of daily steps and perceived social support from family members and
      friends. TRIAL REGISTRATION: Clinicaltrials.gov NCT02850770;
      https://clinicaltrials.gov/ct2/show/NCT02850770 (Archived by WebCite at
      http://www.webcitation.org/query?id=1495567756845570).

PMID- 30291095
TI  - Situation of Diabetes and Related Factors Among Qatari Adults: Findings From a
      Community-Based Survey.
AB  - BACKGROUND: Diabetes mellitus (DM) is a prominent public health problem in Qatar
      with one of the highest prevalence in the Gulf Cooperation Council region.
      Obesity continues to be a challenging public health problem in Qatar along with
      other social determinants contributing to the high DM prevalence. OBJECTIVE: This
      paper examines the data from Qatar National STEPS survey (2012) to determine
      diabetes prevalence among Qatari adults and identify the effect of both
      generalized and central obesity on it. The article also describes the
      contribution of selected social and demographic factors on diabetes prevalence in
      Qatar. METHODS: Secondary data analysis of 1471 Qatari adults (18-64 years) from
      STEP 3 component of the 2012 STEPS Survey was executed. Multivariate binary
      logistic regression analysis was carried out to assess the role of social and
      biomedical factors in the prevalence of DM. RESULTS: Among participants, 18.97%
      (279/1471) of the study population had DM. Both generalized (OR 1.8, P=.005) and
      central obesity (OR 1.9, P<.001) were significantly associated with DM when
      adjusted for various respondent characteristics. Older age (P<.001), marital
      status of ever married (P<.001), and lower educational status (P=.01) were
      associated with DM. Hypertension (OR 1.5, P=.003 total cholesterol level >=190
      mg/dL (OR 2.2, P<.001) and triglyceride level >=150 mg/dL (OR 3.6, P<.001) were
      significantly associated with DM among the study participants. Although family
      history of DM was significantly associated with development of DM (OR 1.7,
      P=.01), parental consanguinity was not associated with DM (OR 0.96, P=.80).
      CONCLUSIONS: The DM prevalence in Qatar seems to be highly associated with
      obesity; however, various additional population characteristics and comorbidity
      factors should also require attention and should be incorporated while developing
      intervention strategies.

PMID- 30291096
TI  - iOS Appstore-Based Phone Apps for Diabetes Management: Potential for Use in
      Medication Adherence.
AB  - BACKGROUND: Currently, various phone apps have been developed to assist patients.
      Many of these apps are developed to assist patients in the self-management of
      chronic diseases such as diabetes. It is essential to analyze these various apps
      to understand the key features that would potentially be instrumental in helping
      patients successfully achieve goals in disease self-management. OBJECTIVE: The
      objective of this study was to conduct a review of all the available diabetes
      related apps in the iOS App Store to evaluate which diabetic app is more
      interactive and offers a wide variety of operations such as monitoring glucose,
      water, carbohydrate intake, weight, body mass index (BMI), medication, blood
      pressure (BP) levels, reminders or push notifications, food database, charts,
      exercise management, email, sync between devices, syncing data directly to the
      prescribers, and other miscellaneous functions such as (Twitter integration,
      password protection, retina display, barcode scanner, apple watch functionality,
      and cloud syncing). METHODS: Data was gathered using the iOS App Store on an
      iPad. The search term "diabetes" resulted in 1209 results. Many of the results
      obtained were remotely related to diabetes and focused mainly on diet, exercise,
      emergency services, refill reminders, providing general diabetes information, and
      other nontherapeutic options. We reviewed each app description and only included
      apps that were meant for tracking blood glucose levels. All data were obtained in
      one sitting by one person on the same device, as we found that carrying out the
      search at different times or on different devices (iPhones) resulted in varying
      results. Apps that did not have a feature for tracking glucose levels were
      excluded from the study. RESULTS: The search resulted in 1209 results; 85 apps
      were retained based on the inclusion criteria mentioned above. All the apps were
      reviewed for average customer ratings, number of reviews, price, and functions.
      Of all the apps surveyed, 18 apps with the highest number of user ratings were
      used for in-depth analysis. Of these 18 apps, 50% (9/18) also had a medication
      adherence function. Our analysis revealed that the Diabetes logbook used by the
      mySugr app was one of the best; it differentiated itself by introducing fun as a
      method of increasing adherence. CONCLUSIONS: A large variation was seen in
      patient ratings of app features. Many patient reviewers desired simplicity of app
      functions. Glucose level tracking and email features potentially helped patients
      and health care providers manage the disease more efficiently. However, none of
      the apps could sync data directly to the prescribers. Additional features such as
      graph customization, availability of data backup, and recording previous entries
      were also requested by many users. Thus, the use of apps in disease management
      and patient and health-care provider involvement in future app refinement and
      development should be encouraged.

PMID- 30291097
TI  - Design and Development of a Context-Aware Knowledge-Based Module for Identifying
      Relevant Information and Information Gaps in Patients With Type 1 Diabetes Self
      Collected Health Data.
AB  - BACKGROUND: Patients with diabetes use an increasing number of self-management
      tools in their daily life. However, health institutions rarely use the data
      generated by these services mainly due to (1) the lack of data reliability, and
      (2) medical workers spending too much time extracting relevant information from
      the vast amount of data produced. This work is part of the FullFlow project,
      which focuses on self-collected health data sharing directly between patients'
      tools and EHRs. OBJECTIVE: The main objective is to design and implement a
      prototype for extracting relevant information and documenting information gaps
      from self-collected health data by patients with type 1 diabetes using a context
      aware approach. The module should permit (1) clinicians to assess the reliability
      of the data and to identify issues to discuss with their patients, and (2)
      patients to understand the implication their lifestyle has on their disease.
      METHODS: The identification of context and the design of the system relied on (1)
      2 workshops in which the main author participated, 1 patient with type 1
      diabetes, and 1 clinician, and (2) a co-design session involving 5 patients with
      type 1 diabetes and 4 clinicians including 2 endocrinologists and 2 diabetes
      nurses. The software implementation followed a hybrid agile and waterfall
      approach. The testing relied on load, and black and white box methods. RESULTS:
      We created a context-aware knowledge-based module able to (1) detect potential
      errors, and information gaps from the self-collected health data, (2) pinpoint
      relevant data and potential causes of noticeable medical events, and (3)
      recommend actions to follow to improve the reliability of the data issues and
      medical issues to be discussed with clinicians. The module uses a reasoning
      engine following a hypothesize-and-test strategy built on a knowledge base and
      using contextual information. The knowledge base contains hypotheses, rules, and
      plans we defined with the input of medical experts. We identified a large set of
      contextual information: emotional state (eg, preferences, mood) of patients and
      medical workers, their relationship, their metadata (eg, age, medical specialty),
      the time and location of usage of the system, patient-collected data (eg, blood
      glucose, basal-bolus insulin), patients' goals and medical standards (eg, insulin
      sensitivity factor, in range values). Demonstrating the usage of the system
      revealed that (1) participants perceived the system as useful and relevant for
      consultation, and (2) the system uses less than 30 milliseconds to treat new
      cases. CONCLUSIONS: Using a knowledge-based system to identify anomalies
      concerning the reliability of patients' self-collected health data to provide
      information on potential information gaps and to propose relevant medical
      subjects to discuss or actions to follow could ease the introduction of self
      collected health data into consultation. Combining this reasoning engine and the
      system of the FullFlow project could improve the diagnostic process in health
      care.

PMID- 30291098
TI  - Experiences of Using Web-Based and Mobile Technologies to Support Self-Management
      of Type 2 Diabetes: Qualitative Study.
AB  - BACKGROUND: The prevalence of type 2 diabetes is rising, placing increasing
      strain on health care services. Web-based and mobile technologies can be an
      important source of information and support for people with type 2 diabetes and
      may prove beneficial with respect to reducing complications due to mismanagement.
      To date, little research has been performed to gain an insight into people's
      perspectives of using such technologies in their daily management. OBJECTIVE: The
      purpose of this study was to understand the impact of using Web-based and mobile
      technologies to support the management of type 2 diabetes. METHODS: In-depth
      interviews were conducted with 15 people with type 2 diabetes to explore
      experiences of using Web-based and mobile technologies to manage their diabetes.
      Transcripts were analyzed using the framework method. RESULTS: Technology
      supported the users to maintain individualized and tailored goals when managing
      their health. A total of 7 themes were identified as important to participants
      when using technology to support self-management: (1) information, (2)
      understanding individual health and personal data, (3) reaching and sustaining
      goals, (4) minimizing disruption to daily life, (5) reassurance, (6)
      communicating with health care professionals, and (7) coordinated care.
      CONCLUSIONS: Patients need to be supported to manage their condition to improve
      well-being and prevent diabetes-related complications from arising. Technologies
      enabled the users to get an in-depth sense of how their body reacted to both
      lifestyle and medication factors-something that was much more difficult with the
      use of traditional standardized information alone. It is intended that the
      results of this study will inform a new questionnaire designed to assess self
      management in people using Web-based and mobile technology to manage their
      health.

PMID- 30291099
TI  - Clinically Excellent Use of the Electronic Health Record: Review.
AB  - BACKGROUND: The transition to the electronic health record (EHR) has brought
      forth a rapid cultural shift in the world of medicine, presenting both new
      challenges as well as opportunities for improving health care. As clinicians work
      to adapt to the changes imposed by the EHR, identification of best practices
      around the clinically excellent use of the EHR is needed. OBJECTIVE: Using the
      domains of clinical excellence previously defined by the Johns Hopkins Miller
      Coulson Academy of Clinical Excellence, this review aims to identify best
      practices around the clinically excellent use of the EHR. METHODS: The authors
      searched the PubMed database, using keywords related to clinical excellence
      domains and the EHR, to capture the English-language, peer-reviewed literature
      published between January 1, 2000, and August 2, 2016. One author independently
      reviewed each article and extracted relevant data. RESULTS: The search identified
      606 titles, with the majority (393/606, 64.9%) in the domain of communication and
      interpersonal skills. Twenty-eight of the 606 (4.6%) titles were excluded from
      full-text review, primarily due to lack of availability of the full-text article.
      The remaining 578 full-text articles reviewed were related to clinical excellence
      generally (3/578, 0.5%) or the specific domains of communication and
      interpersonal skills (380/578, 65.7%), diagnostic acumen (31/578, 5.4%), skillful
      negotiation of the health care system (4/578, 0.7%), scholarly approach to
      clinical practice (41/578, 7.1%), professionalism and humanism (2/578, 0.4%),
      knowledge (97/578, 16.8%), and passion for clinical medicine (20/578, 3.5%).
      CONCLUSIONS: Results suggest that as familiarity and expertise are developed,
      clinicians are leveraging the EHR to provide clinically excellent care. Best
      practices identified included deliberate physical configuration of the clinical
      space to involve sharing the screen with patients and limiting EHR use during
      difficult and emotional topics. Promising horizons for the EHR include the
      ability to augment participation in pragmatic trials, identify adverse drug
      effects, correlate genomic data to clinical outcomes, and follow data-driven
      guidelines. Clinician and patient satisfaction with the EHR has generally
      improved with time, and hopefully continued clinician, and patient input will
      lead to a system that satisfies all.

PMID- 30291100
TI  - Web-Based Weight Loss Intervention for Men With Type 2 Diabetes: Pilot Randomized
      Controlled Trial.
AB  - BACKGROUND: Rising obesity levels remain a major public health concern due to the
      clear link with several comorbidities such as diabetes. Diabetes now affects 6%
      of the UK population. Modest weight loss of 5% to 10% has been shown to be
      associated with significant reductions in blood sugar, lipid, and blood pressure
      levels. Men have been shown to be attracted to programs that do not require
      extensive face-to-face time commitments, illustrating the potential audience
      available for health behavior change via the Web. OBJECTIVE: The objective of our
      study was to evaluate the feasibility and acceptability of a Web-based weight
      loss intervention in men with type 2 diabetes. METHODS: We conducted a pilot,
      parallel 2-arm, individually randomized controlled trial with embedded process
      evaluation. Participants were randomly assigned in a one-to-one ratio to the
      usual care group or the 12-month Web-based weight loss intervention, including
      dietitian and exercise expert feedback. Face-to-face recruitment and assessment
      were performed by the researcher unblinded. Data collected included weight,
      height, body mass index (BMI), and waist circumference, together with an audit
      trail of eligibility, recruitment, retention, and adherence rates. A process
      evaluation (website use data and qualitative interviews) monitored adherence,
      acceptability, and feasibility of the intervention. RESULTS: General practice
      database searches achieved the recruitment target (n=61) for the population of
      men with type 2 diabetes, of whom 66% (40/61) completed 3-month follow-up
      measurements. By 12 months, the retention rate was 52% (32/61), with 12 of the 33
      men allocated to the intervention group still active on the website. The
      intervention was seen as acceptable by the majority of participants. We gained
      insights about acceptability and use of the website from the parallel process
      evaluation. CONCLUSIONS: Recruitment to the Web-based weight loss intervention
      was successful. Results are descriptive, but there were positive indications of
      increased weight loss (in kilograms and as a percentage), and reduced waist
      circumference and BMI for the intervention group from 3 to 12 months, in
      comparison with control. This research adds to the evidence base in relation to
      incorporating a Web-based weight loss intervention within the UK National Health
      Service (NHS). NHS weight loss services are struggling to provide sufficient
      referrals. Therefore, alternative modes of delivery, with the potential to reduce
      health professional input and time per patient while still enabling individual
      and tailored care, need to be investigated to identify whether they can be
      effective and thus benefit the NHS. TRIAL REGISTRATION: International Standard
      Randomized Controlled Trial Number (ISRCTN): 48086713;
      http://www.isrctn.com/ISRCTN48086713 (Archived by WebCite at
      http://www.webcitation.org/6rO4xSlhI).

PMID- 30291102
TI  - CQC-style inspections don't raise standards or improve patient safety, say RCGP
      members.

PMID- 30291103
TI  - Locum GP struck off after sexually motivated behaviour.

PMID- 30291101
TI  - Establishing a Demographic, Development and Environmental Geospatial Surveillance
      Platform in India: Planning and Implementation.
AB  - BACKGROUND: Inadequate administrative health data, suboptimal public health
      infrastructure, rapid and unplanned urbanization, environmental degradation, and
      poor penetration of information technology make the tracking of health and well
      being of populations and their social determinants in the developing countries
      challenging. Technology-integrated comprehensive surveillance platforms have the
      potential to overcome these gaps. OBJECTIVE: This paper provides methodological
      insights into establishing a geographic information system (GIS)-integrated,
      comprehensive surveillance platform in rural North India, a resource-constrained
      setting. METHODS: The International Clinical Epidemiology Network Trust
      International established a comprehensive SOMAARTH Demographic, Development, and
      Environmental Surveillance Site (DDESS) in rural Palwal, a district in Haryana,
      North India. The surveillance platform evolved by adopting four major steps: (1)
      site preparation, (2) data construction, (3) data quality assurance, and (4) data
      update and maintenance system. Arc GIS 10.3 and QGIS 2.14 software were employed
      for geospatial data construction. Surveillance data architecture was built upon
      the geospatial land parcel datasets. Dedicated software (SOMAARTH-1) was
      developed for handling high volume of longitudinal datasets. The built
      infrastructure data pertaining to land use, water bodies, roads, railways,
      community trails, landmarks, water, sanitation and food environment, weather and
      air quality, and demographic characteristics were constructed in a relational
      manner. RESULTS: The comprehensive surveillance platform encompassed a population
      of 0.2 million individuals residing in 51 villages over a land mass of 251.7 sq
      km having 32,662 households and 19,260 nonresidential features (cattle shed,
      shops, health, education, banking, religious institutions, etc). All land parcels
      were assigned georeferenced location identification numbers to enable space and
      time monitoring. Subdivision of villages into sectors helped identify socially
      homogenous community clusters (418/676, 61.8%, sectors). Water and hygiene
      parameters of the whole area were mapped on the GIS platform and quantified. Risk
      of physical exposure to harmful environment (poor water and sanitation
      indicators) was significantly associated with the caste of individual household
      (P=.001), and the path was mediated through the socioeconomic status and density
      of waste spots (liquid and solid) of the sector in which these households were
      located. Ground-truthing for ascertaining the land parcel level accuracies,
      community involvement in mapping exercise, and identification of small
      habitations not recorded in the administrative data were key learnings.
      CONCLUSIONS: The SOMAARTH DDESS experience allowed us to document and explore
      dynamic relationships, associations, and pathways across multiple levels of the
      system (ie, individual, household, neighborhood, and village) through a
      geospatial interface. This could be used for characterization and monitoring of a
      wide range of proximal and distal determinants of health.

PMID- 30291104
TI  - Can patient and carers' experiences shape services?
AB  - Dementia is an increasingly recognised medical condition which, towards its later
      stages, leads to the manifestation of symptoms that often require palliation.
      Hospice admission for patients with dementia has been shown to increase caregiver
      satisfaction. Yet, admission can be harmful for the patient. This feature follows
      the case of one patient, Mr Smith, who was admitted to Royal Trinity Hospice
      (RTH) for symptom control, along with providing respite for his carers. Shortly
      into Mr Smith's admission, he became increasingly agitated and was ultimately
      discharged home. After investigating the cause of early discharge, it was
      concluded that the newly built, modernised private rooms were in fact very
      dissimilar to the homes of patients with dementia. Adapting the clinical
      environment to improve patient and carer satisfaction has been explored in
      numerous studies. Significant amendments used by hospices and care homes include
      bold signs and natural lighting to facilitate way-finding, in addition to vintage
      furnishings to create a sense of familiarity. Taking recent evidence into
      consideration, RTH designed a new dementia-friendly bay situated on the ground
      floor of its inpatient unit. Since then, many other patients with dementia have
      been admitted to the hospice, one being Mr Thomas. Unlike Mr Smith, Mr Thomas was
      much more relaxed during his admission and his wife commented on how pleased she
      was with his care. This feature demonstrates the importance of being receptive to
      feedback and identifying the need for change.

PMID- 30291105
TI  - Implications of epigenetic drift in colorectal neoplasia.
AB  - Many normal tissues undergo age-related drift in DNA methylation, providing a
      quantitative measure of tissue age. Here we identify and validate 781 CpG-islands
      (CGI) that undergo significant methylomic drift in 232 normal colorectal tissues
      and show that these CGI continue to drift in neoplasia while retaining
      significant correlations across samples. However, compared with normal colon,
      this drift advanced (~3-4 fold) faster in neoplasia, consistent with increased
      cell proliferation during neoplastic progression. The observed drift patterns
      were broadly consistent with modeled adenoma-carcinoma sojourn time distributions
      from colorectal cancer (CRC) incidence data. These results support the hypothesis
      that, beginning with the founder premalignant cell, cancer precursors frequently
      sojourn for decades before turning into cancer, implying that the founder cell
      typically arises early in life. At least 77-89% of the observed drift variance in
      distal and rectal tumors was explained by stochastic variability associated with
      neoplastic progression, while only 55% of the variance was explained for proximal
      tumors. However, gene-CGI pairs in the proximal colon that underwent drift were
      significantly and primarily negatively correlated with cancer gene expression,
      suggesting that methylomic drift participates in the clonal evolution of CRC.
      Methylomic drift advanced in colorectal neoplasia consistent with extended
      sojourn time distributions, which accounts for a significant fraction of
      epigenetic heterogeneity in CRC. Importantly, these estimated long-duration
      premalignant sojourn times suggest that early dietary and lifestyle interventions
      may be more effective than later changes in reducing CRC incidence.

PMID- 30291107
TI  - Multi-environment Genomic Prediction of Plant Traits Using Deep Learners with
      Dense Architecture.
AB  - Genomic selection is revolutionizing plant breeding and therefore methods that
      improve prediction accuracy are useful. For this reason, active research is being
      conducted to build and test methods from other areas and adapt them to the
      context of genomic selection. In this paper we explore the novel deep learning
      (DL) methodology in the context of genomic selection. We compared DL methods with
      densely connected network architecture to one of the most often used genome
      enabled prediction models: Genomic Best Linear Unbiased Prediction (GBLUP). We
      used nine published real genomic data sets to compare a fraction of all possible
      deep learning models to obtain a "meta picture" of the performance of DL methods
      with densely connected network architecture. In general, the best predictions
      were obtained with the GBLUP model when genotype*environment interaction (G*E)
      was taken into account (8 out of 9 data sets); when the interactions were
      ignored, the DL method was better than the GBLUP in terms of prediction accuracy
      in 6 out of the 9 data sets. For this reason, we believe that DL should be added
      to the data science toolkit of scientists working on animal and plant breeding.
      This study corroborates the view that there are no universally best prediction
      machines.

PMID- 30291108
TI  - Multi-trait, Multi-environment Deep Learning Modeling for Genomic-Enabled
      Prediction of Plant Traits.
AB  - Multi-trait and multi-environment data are common in animal and plant breeding
      programs. However, what is lacking are more powerful statistical models that can
      exploit the correlation between traits to improve prediction accuracy in the
      context of genomic selection (GS). Multi-trait models are more complex than
      univariate models and usually require more computational resources, but they are
      preferred because they can exploit the correlation between traits, which many
      times helps improve prediction accuracy. For this reason, in this paper we
      explore the power of multi-trait deep learning (MTDL) models in terms of
      prediction accuracy. The prediction performance of MTDL models was compared to
      the performance of the Bayesian multi-trait and multi-environment (BMTME) model
      proposed by Montesinos-Lopez et al. (2016), which is a multi-trait version of the
      genomic best linear unbiased prediction (GBLUP) univariate model. Both models
      were evaluated with predictors with and without the genotype environment
      interaction term. The prediction performance of both models was evaluated in
      terms of Pearson's correlation using cross-validation. We found that the best
      predictions in two of the three data sets were found under the BMTME model, but
      in general the predictions of both models, BTMTE and MTDL, were similar. Among
      models without the genotype environment interaction, the MTDL model was the best,
      while among models with genotype environment interaction, the BMTME model was
      superior. These results indicate that the MTDL model is very competitive for
      performing predictions in the context of GS, with the important practical
      advantage that it requires less computational resources than the BMTME model.

PMID- 30291109
TI  - Role of Cis, Trans, and Inbreeding Effects on Meiotic Recombination in
      Saccharomyces cerevisiae.
AB  - Meiotic recombination is a major driver of genome evolution by creating new
      genetic combinations. To probe the factors driving variability of meiotic
      recombination, we used a high-throughput method to measure recombination rates in
      hybrids between SK1 and a total of 26 Saccharomyces cerevisiae strains from
      different geographic origins and habitats. Fourteen intervals were monitored for
      each strain, covering chromosomes VI and XI entirely, and part of chromosome I.
      We found an average number of crossovers per chromosome ranging between 1.0 and
      9.5 across strains ("domesticated" or not), which is higher than the average
      between 0.5 and 1.5 found in most organisms. In the different intervals analyzed,
      recombination showed up to ninefold variation across strains but global
      recombination landscapes along chromosomes varied less. We also built an
      incomplete diallel experiment to measure recombination rates in one region of
      chromosome XI in 10 different crosses involving five parental strains. Our
      overall results indicate that recombination rate is increasingly positively
      correlated with sequence similarity between homologs (i) in DNA double-strand
      break-rich regions within intervals, (ii) in entire intervals, and (iii) at the
      whole genome scale. Therefore, these correlations cannot be explained by cis
      effects only. We also estimated that cis and trans effects explained 38 and 17%,
      respectively, of the variance of recombination rate. In addition, by using a
      quantitative genetics analysis, we identified an inbreeding effect that reduces
      recombination rate in homozygous genotypes, while other interaction effects
      (specific combining ability) or additive effects (general combining ability) are
      found to be weak. Finally, we measured significant crossover interference in some
      strains, and interference intensity was positively correlated with crossover
      number.

PMID- 30291110
TI  - Integration of Stress Signaling in Caenorhabditis elegans Through Cell
      Nonautonomous Contributions of the JNK Homolog KGB-1.
AB  - Dealing with physiological stress is a necessity for all organisms, and the
      pathways charged with this task are highly conserved in Metazoa . Accumulating
      evidence highlights cell-nonautonomous activation as an important mode of
      integrating stress responses at the organism level. Work in Caenorhabditis
      elegans highlighted the importance of such regulation for the unfolded protein
      response (UPR) and for gene expression downstream of the longevity-associated
      transcription factor DAF-16 Here we describe a role for the JNK homolog KGB-1 in
      cell-nonautonomous regulation of these two response modules. KGB-1 protects
      developing larvae from heavy metals and from protein folding stress (which we
      found to be independent of canonical UPR pathways), but sensitizes adults to the
      same stress, further shortening life span under normal conditions. This switch is
      associated with age-dependent antagonistic regulation of DAF-16 Using transgenic
      tissue-specific KGB-1 expression or tissue-specific KGB-1 activation we examined
      the contributions of KGB-1 to gene regulation, stress resistance, and life span.
      While cell-autonomous contributions were observed, particularly in the epidermis,
      cell-nonautonomous contributions of neuronal KGB-1 (and also in muscle) were
      effective in driving intestinal gene induction, age-dependent regulation of
      intestinal DAF-16, and stress resistance, and did not require KGB-1 expression in
      the target tissue. Additional genetic analyses revealed requirement for UNC-13 in
      mediating neuronal contributions, indicating involvement of neurotransmission.
      Our results expand the role of KGB-1 in stress responses from providing local
      cellular protection to integrating stress responses at the level of the whole
      organism.

PMID- 30291106
TI  - Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the
      American Diabetes Association (ADA) and the European Association for the Study of
      Diabetes (EASD).
AB  - The American Diabetes Association and the European Association for the Study of
      Diabetes convened a panel to update the prior position statements, published in
      2012 and 2015, on the management of type 2 diabetes in adults. A systematic
      evaluation of the literature since 2014 informed new recommendations. These
      include additional focus on lifestyle management and diabetes self-management
      education and support. For those with obesity, efforts targeting weight loss,
      including lifestyle, medication, and surgical interventions, are recommended.
      With regards to medication management, for patients with clinical cardiovascular
      disease, a sodium-glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like
      peptide 1 (GLP-1) receptor agonist with proven cardiovascular benefit is
      recommended. For patients with chronic kidney disease or clinical heart failure
      and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven
      benefit is recommended. GLP-1 receptor agonists are generally recommended as the
      first injectable medication.

PMID- 30291111
TI  - Proteomic profiling identifies outcome-predictive markers in patients with
      peripheral T-cell lymphoma, not otherwise specified.
AB  - Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) constitutes a
      heterogeneous category of lymphomas, which do not fit into any of the
      specifically defined T-cell lymphoma entities. Both the pathogenesis and tumor
      biology in PTCL-NOS are poorly understood. Protein expression in pretherapeutic
      PTCL-NOS tumors was analyzed by proteomics. Differentially expressed proteins
      were compared in 3 distinct scenarios: (A) PTCL-NOS tumor tissue (n = 18) vs
      benign lymphoid tissue (n = 8), (B) clusters defined by principal component
      analysis (PCA), and (C) tumors from patients with chemosensitive vs refractory
      PTCL-NOS. Selected differentially expressed proteins identified by proteomics
      were correlated with clinico-pathological features and outcome in a larger cohort
      of patients with PTCL-NOS (n = 87) by immunohistochemistry (IHC). Most proteins
      with altered expression were identified comparing PTCL-NOS vs benign lymphoid
      tissue. PCA of the protein profile defined 3 distinct clusters. All benign
      samples clustered together, whereas PTCL-NOS tumors separated into 2 clusters
      with different patient overall survival rates (P = .001). Differentially
      expressed proteins reflected large biological diversity among PTCL-NOS,
      particularly associated with alterations of "immunological" pathways. The 2 PTCL
      NOS subclusters defined by PCA showed disturbance of "stress-related" and
      "protein metabolic" pathways. alpha-Enolase 1 (ENO1) was found differentially
      expressed in all 3 analyses, and high intratumoral ENO1 expression evaluated by
      IHC correlated with poor outcome (hazard ratio, 2.09; 95% confidence interval,
      1.17-3.73; P = .013). High expression of triosephosphate isomerase (TPI1) also
      showed a tendency to correlate with poor survival (P = .057). In conclusion,
      proteomic profiling of PTCL-NOS provided evidence of markedly altered protein
      expression and identified ENO1 as a novel potential prognostic marker.

PMID- 30291112
TI  - Eculizumab in cold agglutinin disease (DECADE): an open-label, prospective,
      bicentric, nonrandomized phase 2 trial.
AB  - Cold agglutinin disease (CAD) is a complement-dependent disorder, with
      extravascular and intravascular hemolysis resulting from initial or terminal
      complement activation, respectively. We tested the efficacy and safety of
      eculizumab, an inhibitor of the terminal complement pathway. Treatment-requiring
      patients received 600 mg eculizumab weekly for 4 weeks, followed 1 week later by
      900 mg every other week through week 26. The primary end point was the difference
      in the lactate dehydrogenase level between the first and the last day of therapy.
      Twelve patients with chronic CAD and 1 patient with an acute cold agglutinin
      syndrome were included. The median lactate dehydrogenase level decreased from 572
      U/L (interquartile range [IQR], 534-685) to 334 U/L (IQR, 243-567; P = .0215),
      paralleled by an increase in hemoglobin from 9.35 g/dL (IQR, 8.80-10.80) to 10.15
      g/dL (IQR, 9.00-11.35; P = .0391; Wilcoxon signed-rank test). Three patients
      maintained and 8 patients acquired transfusion independence, and 1 patient each
      showed a reduced or increased transfusion requirement, respectively (P = .0215;
      exact McNemar's test). Patients with cold agglutinins with a thermal amplitude of
      37 degrees C tended to have less pronounced lactate dehydrogenase responses than
      patients with cold agglutinins with narrower thermal amplitudes. In the latter,
      responses were observed at lower serum levels of eculizumab than they were in the
      former. In contrast to hemolysis, cold-induced circulatory symptoms remained
      unaffected. In conclusion, eculizumab significantly reduced hemolysis and
      transfusion requirement in patients with CAD. Suppression of hemolysis caused by
      cold agglutinins with a wide thermal amplitude may require higher eculizumab
      doses than used here. The trial is registered with EudraCT (#2009-016966-97) and
      www.clinicaltrials.gov (#NCT01303952).

PMID- 30291113
TI  - Daratumumab in life-threatening autoimmune hemolytic anemia following
      hematopoietic stem cell transplantation.
AB  - New-onset autoimmune hemolytic anemia (AIHA) occurs in 2% to 6% of pediatric
      patients post-hematopoietic stem cell transplantation (HSCT) and is a significant
      complication. Incomplete immune recovery following HSCT may predispose to immune
      dysregulation including autoimmune cytopenias. We describe an innovative therapy
      for AIHA refractory to proteasome inhibition. In potentially life-threatening
      AIHA in the context of HSCT, daratumumab may be an effective rescue therapy.

PMID- 30291114
TI  - Incremental Elevations in TNFalpha and IL6 in the Human Colon and Procancerous
      Changes in the Mucosal Transcriptome Accompany Adiposity.
AB  - BACKGROUND: Obesity, a risk factor for colorectal cancer, raises systemic levels
      of proinflammatory mediators. Whether increased levels also reside in the colons
      of obese individuals and are accompanied by procancerous alterations in the
      mucosal transcriptome is unknown. METHODS: Concentrations of TNFalpha, IL1beta,
      and IL6 in blood and colonic mucosa of 16 lean and 26 obese individuals were
      examined. Differences in the mucosal transcriptome between the two groups were
      defined. RESULTS: Plasma IL6 and TNFalpha were 1.4- to 3-fold elevated in obese
      subjects [body mass index (BMI) >= 34 kg/m2] compared with the lean controls (P <
      0.01). Among individuals with BMI >= 34 kg/m2 colonic concentrations of IL6 and
      TNFalpha were 2- to 3-fold greater than in lean subjects (P < 0.03). In a general
      linear model, adjusted for NSAID use, colonic IL6 (partial r = 0.41; P < 0.01)
      and TNFalpha (partial r = 0.41; P = 0.01) increased incrementally over the entire
      range of BMIs (18.1-45.7). Regular use of nonsteroidal anti-inflammatory drugs
      (NSAIDs) was associated with a reduction in colonic IL6 (beta = -0.65, P < 0.02).
      RNA sequencing (NSAID users excluded) identified 182 genes expressed
      differentially between lean and obese subjects. The two gene networks most
      strongly linked to changes in expression included several differentially
      expressed genes known to regulate the procarcinogenic signaling pathways,
      NFkappaB and ERK 1/2, in a pattern consistent with upregulation of each in the
      obese subjects. CONCLUSIONS: Incremental increases in two major proinflammatory
      colonic cytokines are associated with increasing BMI, and in the obese state are
      accompanied by procancerous changes in the transcriptome. IMPACT: These
      observations delineate means by which an inflammatory milieu may contribute to
      obesity-promoted colon cancer.

PMID- 30291115
TI  - Primary Colonizing Betaproteobacteriales Play a Key Role in the Growth of
      Legionella pneumophila in Biofilms on Surfaces Exposed to Drinking Water Treated
      by Slow Sand Filtration.
AB  - Slow sand filtration with extensive pretreatment reduces the microbial growth
      potential of drinking water to a minimum level at four surface water supplies in
      The Netherlands. The potential of these slow sand filtrates (SSFs) to promote
      microbial growth in warm tap water installations was assessed by measuring
      biofilm formation and growth of Legionella bacteria on glass and chlorinated
      polyvinylchloride (CPVC) surfaces exposed to SSFs at 37 +/- 2 degrees C in a
      model system for up to six months. The steady-state biofilm concentration ranged
      from 230 to 3,980 pg ATP cm-2 on glass and 1.4 (+/-0.3)-times-higher levels on
      CPVC. These concentrations correlated significantly with the assimilable organic
      carbon (AOC) concentrations of the warm water (8 to 24 ug acetate-C equivalents
      [ac-C eq] liter-1), which were raised about 2 times by mixing cold and heated (70
      degrees C) SSFs. All biofilms supported growth of Legionella pneumophila with
      maximum concentrations ranging from 6 * 102 to 1.5 * 105 CFU cm-2 Biofilms after
      <=50 days of exposure were predominated by Betaproteobacteriales, mainly
      Piscinibacter, Caldimonas, Methyloversatilis, and an uncultured Rhodocyclaceae
      bacterium. These rapidly growing primary colonizers most likely served as prey
      for the host amoebae of L. pneumophila Alphaproteobacteria, mostly
      Xanthobacteraceae, e.g., Bradyrhizobium, Pseudorhodoplanes, and other amoeba
      resistant bacteria, accounted for 37.5% of the clones retrieved. A conceptual
      model based on a quadratic relationship between the L. pneumophila colony count
      and the biofilm concentration under steady-state conditions is used to explain
      the variations in the Legionella CFU pg-1 ATP ratios in the biofilms.IMPORTANCE
      Proliferation of L. pneumophila in premise plumbing poses a public health threat.
      Extended water treatment using physicochemical and biofiltration processes,
      including slow sand filtration, at four surface water supplies in The Netherlands
      reduces the microbial growth potential of the treated water to a minimum level,
      and the distributed drinking water complies with high quality standards. However,
      heating of the water in warm tap water installations increases the concentration
      of easily assimilable organic compounds, thereby promoting biofilm formation and
      growth of L. pneumophila Prevention of biofilm formation in plumbing systems by
      maintenance of a disinfectant residual during distribution and/or further natural
      organic matter (NOM) removal is not feasible in the supplies studied. Temperature
      management in combination with optimized hydraulics and material selection are
      therefore essential to prevent growth of L. pneumophila in premise plumbing
      systems. Still, reducing the concentration of biodegradable compounds in drinking
      water by appropriate water treatment is important for limiting the Legionella
      growth potential.

PMID- 30291116
TI  - Lavender Decline in France Is Associated with Chronic Infection by Lavender
      Specific Strains of "Candidatus Phytoplasma solani".
AB  - Lavender decline compromises French lavender production, and preliminary data
      have suggested the involvement of "Candidatus Phytoplasma solani" in the etiology
      of the disease. In order to evaluate the epidemiological role of "Ca Phytoplasma
      solani," a 3-year survey was conducted in southeastern France. "Ca Phytoplasma
      solani" was detected in 19 to 56% of the declining plants, depending on seasons
      and cultivars, and its prevalence was correlated with symptom severity. Autumn
      was more favorable than spring for phytoplasma detection, and "Ca Phytoplasma
      solani" incidence was higher in Lavandula angustifolia than in Lavandula
      intermedia hybrids. Detection of the phytoplasma fluctuated over months,
      supporting the chronicity of infection. Three "Ca Phytoplasma solani" secY
      genotypes, S17, S16, and S14, were the most prevalent in lavender fields and were
      also detected in nurseries, whereas strains detected in surrounding bindweed and
      wild carrots were mostly of the S1 and S4 genotypes. This suggests that lavender
      is the main pathogen reservoir of the epidemic. Adults and nymphs of the
      planthopper vector Hyalesthes obsoletus were commonly captured in lavender fields
      and were shown to harbor mainly the prevalent phytoplasma genotypes detected in
      lavenders. The "Ca Phytoplasma solani" genotype S17 was transmitted to
      Catharanthus roseus periwinkle by naturally infected H. obsoletus Finally, the
      inventory of the bacterial community of declining lavenders that tested negative
      for "Ca Phytoplasma solani" by 16S rRNA deep sequencing ruled out the involvement
      of other phloem-limited bacterial pathogens.IMPORTANCE The etiology and main
      pathways for the spread of lavender decline, an infectious disease affecting
      French lavender production since the 1960s, have remained unclear, hampering the
      development of efficient control strategies. An extensive survey of lavender
      fields led to the conclusion that "Candidatus Phytoplasma solani" was chronically
      infecting declining lavenders and was associated with large infectious
      populations of Hyalesthes obsoletus planthoppers living on the crop itself.
      Lavender appeared to be the main reservoir host for lavender-specific phytoplasma
      strains, an unusual feature for this phytoplasma, which usually propagates from
      reservoir weeds to various economically important crops. These results point out
      the necessity to protect young lavender fields from the initial phytoplasma
      inoculum coming from surrounding lavender fields or from infected nurseries and
      to promote agricultural practices that reduce the development of H. obsoletus
      vector populations.

PMID- 30291117
TI  - Behavior of Foodborne Pathogens Listeria monocytogenes and Staphylococcus aureus
      in Mixed-Species Biofilms Exposed to Biocides.
AB  - In nature and man-made environments, microorganisms reside in mixed-species
      biofilms, in which the growth and metabolism of an organism are different from
      these behaviors in single-species biofilms. Pathogenic microorganisms may be
      protected against adverse treatments in mixed-species biofilms, leading to health
      risk for humans. Here, we developed two mixed five-species biofilms that included
      one or the other of the foodborne pathogens Listeria monocytogenes and
      Staphylococcus aureus The five species, including the pathogen, were isolated
      from a single food-processing environmental sample, thus mimicking the
      environmental community. In mature mixed five-species biofilms on stainless
      steel, the two pathogens remained at a constant level of ~105 CFU/cm2 The mixed
      five-species biofilms as well as the pathogens in monospecies biofilms were
      exposed to biocides to determine any pathogen-protective effect of the mixed
      biofilm. Both pathogens and their associate microbial communities were reduced by
      peracetic acid treatments. S. aureus decreased by 4.6 log cycles in monospecies
      biofilms, but the pathogen was protected in the five-species biofilm and
      decreased by only 1.1 log cycles. Sessile cells of L. monocytogenes were affected
      to the same extent when in a monobiofilm or as a member of the mixed-species
      biofilm, decreasing by 3 log cycles when exposed to 0.0375% peracetic acid. When
      the pathogen was exchanged in each associated microbial community, S. aureus was
      eradicated, while there was no significant effect of the biocide on L.
      monocytogenes or the mixed community. This indicates that particular members or
      associations in the community offered the protective effect. Further studies are
      needed to clarify the mechanisms of biocide protection and to identify the
      species playing the protective role in microbial communities of
      biofilms.IMPORTANCE This study demonstrates that foodborne pathogens can be
      established in mixed-species biofilms and that this can protect them from biocide
      action. The protection is not due to specific characteristics of the pathogen,
      here S. aureus and L. monocytogenes, but likely caused by specific members or
      associations in the mixed-species biofilm. Biocide treatment and resistance are a
      challenge for many industries, and biocide efficacy should be tested on
      microorganisms growing in biofilms, preferably mixed systems, mimicking the
      application environment.

PMID- 30291118
TI  - Effective Soil Extraction Method for Cultivating Previously Uncultured Soil
      Bacteria.
AB  - Here, a new medium, named intensive soil extract medium (ISEM), based on new soil
      extract (NSE) using 80% methanol, was used to efficiently isolate previously
      uncultured bacteria and new taxonomic candidates, which accounted for 49% and 55%
      of the total isolates examined (n = 258), respectively. The new isolates were
      affiliated with seven phyla (Proteobacteria, Acidobacteria, Firmicutes,
      Actinobacteria, Verrucomicrobia, Planctomycetes, and Bacteroidetes). The result
      of chemical analysis showed that NSE included more diverse components of low
      molecular-weight organic substances than two conventional soil extracts made
      using distilled water. Cultivation of previously uncultured bacteria is expected
      to extend knowledge through the discovery of new phenotypic, physiological, and
      functional properties and even roles of unknown genes.IMPORTANCE Both
      metagenomics and single-cell sequencing can detect unknown genes from uncultured
      microbial strains in environments, and either method may find the significant
      potential metabolites and roles of these strains. However, such gene/genome-based
      techniques do not allow detailed investigations that are possible with cultures.
      To solve this problem, various approaches for cultivation of uncultured bacteria
      have been developed, but there are still difficulties in maintaining pure
      cultures by subculture.

PMID- 30291119
TI  - A Simple In Vitro Gut Model for Studying the Interaction between Escherichia coli
      and the Intestinal Commensal Microbiota in Cecal Mucus.
AB  - A novel in vitro gut model was developed to better understand the interactions
      between Escherichia coli and the mouse cecal mucus commensal microbiota. The gut
      model is simple and inexpensive while providing an environment that in large part
      replicates the non-adherent mucus layer of the mouse cecum. 16S ribosomal RNA
      gene profiling of the cecal microbial communities of streptomycin-treated mice
      colonized with E. coli MG1655 or E. coli Nissle 1917 and the gut model confirmed
      that the gut model properly reflected the community structure of the mouse
      intestine. Furthermore, the in vitro gut model mimics the results of published in
      vivo competitive colonization experiments. The gut model is initiated by
      colonization of streptomycin treated mice, then the community is serially
      transferred in microcentrifuge tubes in an anaerobic environment generated in
      anaerobe jars. The nutritional makeup of the cecum is simulated in the gut model
      by using a medium consisting of porcine mucin, mouse cecal mucus, HEPES-Hanks
      buffer (pH 7.2), Cleland's reagent, and agarose. Agarose was found to be
      essential for maintaining stability of the microbial community in the gut model.
      The outcome of competitions between E. coli strains in the in vitro gut model are
      readily explained by the "restaurant hypothesis" of intestinal colonization. This
      simple model system potentially can be used to more fully understand how
      different members of the microbiota interact physically and metabolically during
      colonization of the intestinal mucus layer.Importance Both commensal and
      pathogenic strains of Escherichia coli appear to colonize the mammalian intestine
      by interacting physically and metabolically with other members of the microbiota
      in the mucus layer that overlays the cecal and colonic epithelium. However, the
      use of animal models and complexity of the mammalian gut make it difficult to
      isolate experimental variables that could dictate the interactions between E.
      coli and other members of the microbiota, such as those that are critical for
      successful colonization. Here we describe a simple and relatively inexpensive in
      vitro gut model that in large part mimics in vivo conditions, and therefore can
      facilitate the manipulation of experimental variables for studying interactions
      of E.coli with the intestinal microbiota.

PMID- 30291120
TI  - Response of the Anaerobic Methanotroph "Candidatus Methanoperedens nitroreducens"
      to Oxygen Stress.
AB  - "Candidatus Methanoperedens nitroreducens" is an archaeon that couples the
      anaerobic oxidation of methane to nitrate reduction. In natural and man-made
      ecosystems, this archaeon is often found at oxic-anoxic interfaces where nitrate,
      the product of aerobic nitrification, cooccurs with methane produced by
      methanogens. As such, populations of "Ca Methanoperedens nitroreducens" could be
      prone to regular oxygen exposure. Here, we investigated the effect of 5%
      (vol/vol) oxygen exposure in batch activity assays on a "Ca Methanoperedens
      nitroreducens" culture, enriched from an Italian paddy field. Metagenome
      sequencing of the DNA extracted from the enrichment culture revealed that 83% of
      16S rRNA gene reads were assigned to a novel strain, "Candidatus Methanoperedens
      nitroreducens Verserenetto." RNA was extracted, and metatranscriptome sequencing
      upon oxygen exposure revealed that the active community changed, most notably in
      the appearance of aerobic methanotrophs. The gene expression of "Ca
      Methanoperedens nitroreducens" revealed that the key genes encoding enzymes of
      the methane oxidation and nitrate reduction pathways were downregulated. In
      contrast to this, we identified upregulation of glutaredoxin, thioredoxin
      family/like proteins, rubrerythrins, peroxiredoxins, peroxidase, alkyl
      hydroperoxidase, type A flavoproteins, FeS cluster assembly protein, and cysteine
      desulfurases, indicating the genomic potential of "Ca Methanoperedens
      nitroreducens Verserenetto" to counteract the oxidative damage and adapt in
      environments where they might be exposed to regular oxygen intrusion.IMPORTANCE
      "Candidatus Methanoperedens nitroreducens" is an anaerobic archaeon which couples
      the reduction of nitrate to the oxidation of methane. This microorganism is
      present in a wide range of aquatic environments and man-made ecosystems, such as
      paddy fields and wastewater treatment systems. In such environments, these
      archaea may experience regular oxygen exposure. However, "Ca Methanoperedens
      nitroreducens" is able to thrive under such conditions and could be applied for
      the simultaneous removal of dissolved methane and nitrogenous pollutants in
      oxygen-limited systems. To understand what machinery "Ca Methanoperedens
      nitroreducens" possesses to counteract the oxidative stress and survive, we
      characterized the response to oxygen exposure using a multi-omics approach.

PMID- 30291121
TI  - Improvement of ST0452 N-Acetylglucosamine-1-Phosphate Uridyltransferase Activity
      by the Cooperative Effect of Two Single Mutations Identified through Structure
      Based Protein Engineering.
AB  - We showed previously that the Y97N mutant of the ST0452 protein, isolated from
      Sulfolobus tokodaii, exhibited over 4 times higher N-acetylglucosamine-1
      phosphate (GlcNAc-1-P) uridyltransferase (UTase) activity, compared with that of
      the wild-type ST0452 protein. We determined the three-dimensional structure of
      the Y97N protein to explore the detailed mechanism underlying this increased
      activity. The overall structure was almost identical to that of the wild-type
      ST0452 protein (PDB ID 2GGO), with residue 97 (Asn) interacting with the O-5 atom
      of N-acetylglucosamine (GlcNAc) in the complex without metal ions. The same
      interaction was observed for Escherichia coli GlmU in the absence of metal ions.
      These observations indicated that the three-dimensional structure of the Y97N
      protein was not changed by this substitution but the interactions with the
      substrate were slightly modified, which might cause the activity to increase. The
      crystal structure of the Y97N protein also showed that positions 146 (Glu) and 80
      (Thr) formed interactions with GlcNAc, and an engineering strategy was applied to
      these residues to increase activity. All proteins substituted at position 146 had
      drastically decreased activities, whereas several proteins substituted at
      position 80 showed higher GlcNAc-1-P UTase activity, compared to that of the wild
      type protein. The substituted amino acids at positions 80 and 97 might result in
      optimized interactions with the substrate; therefore, we predicted that the
      combination of these two substitutions might cooperatively increase GlcNAc-1-P
      UTase activity. Of the four double mutant ST0452 proteins generated, T80S/Y97N
      showed 6.5-times-higher activity, compared to that of the wild-type ST0452
      protein, revealing that these two substituted residues functioned cooperatively
      to increase GlcNAc-1-P UTase activity.IMPORTANCE We demonstrated that the
      enzymatic activity of a thermostable protein was over 4 times higher than that of
      the wild-type protein following substitution of a single amino acid, without
      affecting its thermostability. The three-dimensional structure of the improved
      mutant protein complexed with substrate was determined. The same overall
      structure and interaction between the substituted residue and the GlcNAc
      substrate as observed in the well-characterized bacterial enzyme suggested that
      the substitution of Tyr at position 97 by Asn might slightly change the
      interaction. This subtle change in the interaction might potentially increase the
      GlcNAc-1-P UTase activity of the mutant protein. These observations indicated
      that a drastic change in the structure of a natural thermostable enzyme is not
      necessary to increase its activity; a subtle change in the interaction with the
      substrate might be sufficient. Cooperative effects were observed in the
      appropriate double mutant protein. This work provides useful information for the
      future engineering of natural enzymes.

PMID- 30291122
TI  - Feammox Acidimicrobiaceae sp. A6, a lithoautotrophic electrode-colonizing
      bacterium.
AB  - An Acidimicrobiaceae sp. A6 (A6), from the Actinobacteria phylum was recently
      identified as a microorganism that can carry out anaerobic ammonium oxidation
      coupled to iron reduction, a process also known as Feammox. Being an iron
      reducing bacterium, A6 was studied as a potential electrode-reducing bacterium
      that may transfer electrons extracellularly onto electrodes while gaining energy
      from ammonium oxidation. Actinobacteria species have been overlooked as
      electrogenic bacteria, and the importance of lithoautotrophic iron-reducers as
      electrode-reducing bacteria at anodes has not been addressed. By installing
      electrodes in soil of a forested riparian wetland where A6 thrives, in soil
      columns in the laboratory, as well as in A6 bioaugmented constructed wetland (CW)
      mesocosms, and finally operating microbial electrolysis (MECs) cells with pure A6
      culture, characteristics and performances of this organism as an electrode
      reducing bacterium candidate were investigated. In this study, we show that
      Acidimicrobiaceae sp. A6, a lithoautotrophic bacterium, is capable of colonizing
      electrodes under controlled conditions. In addition, A6 appears to be an
      electrode-reducing bacterium since current production was boosted shortly after
      the CWs were seeded with enrichment A6 culture, and current production was
      detected in MECs operated with pure A6, with the anode as the sole electron
      acceptor and NH4 + as the sole electron donor.IMPORTANCE Most studies on
      electrogenic microorganisms have focused on the most abundant heterotrophs, while
      other microorganisms also commonly present in electrode microbial communities
      such as Actinobacteria have been overlooked. The novel Acidimicrobiaceae sp. A6
      (Actinobacteria) is an iron-reducing bacterium that can colonize the surface of
      anodes and is linked to electrical current production, making it an electrode
      reducing bacteria candidate. Furthermore, A6 can carry out anaerobic ammonium
      oxidation coupled to iron reduction, therefore, findings from this study open up
      the possibility of using electrodes instead of iron as electron acceptors as a
      mean to promote A6 to treat NH4 + containing wastewater more efficiently.
      Altogether, this study expands our knowledge on electrogenic bacteria and opens
      up the possibility to develop Feammox-based technologies coupled to bioelectric
      systems for the treatment of NH4 + and other contaminants in anoxic systems.

PMID- 30291123
TI  - Rhizosphere Microbial Response to Multiple Metal(loid)s in Different Contaminated
      Arable Soils Indicates Crop-Specific Metal-Microbe Interactions.
AB  - In this study, we sampled rhizosphere soils from seven different agricultural
      fields adjacent to mining areas and cultivated with different crops (corn, rice,
      or soybean), to study the interactions among the innate microbiota, soil chemical
      properties, plants, and metal contamination. The rhizosphere bacterial
      communities were characterized by Illumina sequencing of the 16S rRNA genes, and
      their interactions with the local environments, including biotic and abiotic
      factors, were analyzed. Overall, these soils were heavily contaminated with
      multiple metal(loid)s, including V, Cr, Cu, Sb, Pb, Cd, and As. The interactions
      between environmental parameters and microbial communities were identified using
      multivariate regression tree analysis, canonical correspondence analysis, and
      network analysis. Notably, metal-microbe interactions were observed to be crop
      specific. The rhizosphere communities were strongly correlated with V and Cr
      levels, although these sites were contaminated from Sb and Zn/Pb mining,
      suggesting that these two less-addressed metals may play important roles in
      shaping the rhizosphere microbiota. Members of Gaiellaceae cooccurred with other
      bacterial taxa (biotic interactions) and several metal(loid)s, suggesting
      potential metal(loid) resistance or cycling involving this less-well-known
      taxon.IMPORTANCE The rhizosphere is the "hub" for plant-microbe interactions and
      an active region for exchange of nutrients and energy between soil and plants. In
      arable soils contaminated by mining activities, the rhizosphere may be an
      important barrier resisting metal uptake. Therefore, the responses of the
      rhizosphere microbiota to metal contamination involve important biogeochemical
      processes, which can affect metal bioavailability and thus impact food safety.
      However, understanding these processes remains a challenge. The current study
      illustrates that metal-microbe interactions may be crop specific and some less
      addressed metals, such as V and Cr, may play important roles in shaping bacterial
      communities. The current study provides new insights into metal-microbe
      interactions and contributes to future implementation and monitoring efforts in
      contaminated arable soils.

PMID- 30291124
TI  - CAR T-cell Therapy for Solid Tumors?
AB  - Scientists have identified a wide variety of challenges preventing the
      development of effective CAR T-cell therapies for solid tumors, but they are
      investigating just as many potential solutions. Progress has been slow, but many
      researchers remain optimistic that successful CAR T-cell therapies, either alone
      or in combination with other treatments, will eventually be developed.

PMID- 30291125
TI  - Neutrophil Extracellular Traps Trigger Dormant Tumor Cell Proliferation.
AB  - Inflammation-induced neutrophil extracellular traps (NET) awaken dormant cells to
      promote metastasis.

PMID- 30291126
TI  - Epacadostat plus Pembrolizumab Is Well Tolerated in a Phase I Trial.
AB  - Epacadostat plus pembrolizumab achieved responses in 40% of patients with
      advanced solid tumors.

PMID- 30291127
TI  - A Rethink for IO Biomarkers.
AB  - Predictive biomarkers of immunotherapy are growing increasingly complex
      incorporating aspects of tumor-intrinsic, immune microenvironmental, and host
      related biology-and several new initiatives aim to establish standards for the
      field to ensure consistency of commercial assays going forward.

PMID- 30291128
TI  - Defective Nuclear Envelope Assembly May Promote Mitotic Errors.
AB  - Defective assembly of the nuclear envelope and nuclear pore complex in
      micronuclei may underlie chromothripsis.

PMID- 30291129
TI  - Lurbinectedin Is Active in Patients with BRCA1/2 Mutant Breast Cancer.
AB  - A phase II trial evaluated lurbinectedin in patients with BRCA1/2-mutant and wild
      type tumors.

PMID- 30291130
TI  - Emergence of immunoregulatory Ym1+Ly6Chi monocytes during recovery phase of
      tissue injury.
AB  - Ly6Chi monocytes migrate to injured sites and induce inflammation in the acute
      phase of tissue injury. However, once the causes of tissue injury are eliminated,
      monocyte-derived macrophages contribute to the resolution of inflammation and
      tissue repair. It remains unclear whether the emergence of these immunoregulatory
      macrophages is attributed to the phenotypic conversion of inflammatory monocytes
      in situ or to the recruitment of bone marrow-derived regulatory cells de novo.
      Here, we identified a subpopulation of Ly6Chi monocytes that contribute to the
      resolution of inflammation and tissue repair. Ym1+Ly6Chi monocytes greatly
      expanded in bone marrow during the recovery phase of systemic inflammation or
      tissue injury. Ym1+Ly6Chi monocytes infiltrating into an injured site exhibited
      immunoregulatory and tissue-reparative phenotypes. Deletion of Ym1+Ly6Chi
      monocytes resulted in delayed recovery from colitis. These results demonstrate
      that a distinct monocyte subpopulation destined to act in immunoregulation is
      generated in bone marrow and participates in resolution of inflammation and
      tissue repair.

PMID- 30291131
TI  - The cysteinyl leukotriene 3 receptor regulates expansion of IL-25-producing
      airway brush cells leading to type 2 inflammation.
AB  - Respiratory epithelial cells (EpCs) orchestrate airway mucosal inflammation in
      response to diverse environmental stimuli, but how distinct EpC programs are
      regulated remains poorly understood. Here, we report that inhalation of
      aeroallergens leads to expansion of airway brush cells (BrCs), specialized
      chemosensory EpCs and the dominant epithelial source of interleukin-25 (IL-25).
      BrC expansion was attenuated in mice lacking either LTC4 synthase, the
      biosynthetic enzyme required for cysteinyl leukotriene (CysLT) generation, or the
      EpC receptor for leukotriene E4 (LTE4), CysLT3R. LTE4 inhalation was sufficient
      to elicit CysLT3R-dependent BrC expansion in the murine airway through an IL-25
      dependent but STAT6-independent signaling pathway. Last, blockade of IL-25
      attenuated both aeroallergen and LTE4-elicited CysLT3R-dependent type 2 lung
      inflammation. These results demonstrate that CysLT3R senses the endogenously
      generated lipid ligand LTE4 and regulates airway BrC number and function.

PMID- 30291132
TI  - Airway brush cells: Not as "tuft" as you might think.
AB  - The leukotriene E4 receptor CysLT3R regulates expansion of chemosensory brush
      cells and production of interleukin-25 in the airways.

PMID- 30291133
TI  - Checking into the germinal centers: PD-1 regulates entry.
AB  - PD-1 functions on T follicular helper cells to dictate localization within lymph
      node germinal centers.

PMID- 30291134
TI  - B cells drive auto-T cells to the brain.
AB  - Self-reactive T cells that traffic to the brain tissue of patients with multiple
      sclerosis are driven by antigen-experienced B cells.

PMID- 30291135
TI  - Lost in Translation: Deciphering the Mechanism of Action of Anti-human CTLA-4.
AB  - Despite a number of preclinical studies demonstrating that the activity of anti
      CTLA-4 antibodies in murine models of cancer relies on effector T-cell activation
      and regulatory T cell depletion, the activity of the clinical antibodies remains
      controversial. To decipher such mechanisms is critical to the development of
      novel and more potent immunotherapies. Clin Cancer Res; 1-3. (c)2018 AACR. See
      related article by Sharma et al.

PMID- 30291136
TI  - Prevalence of cystoid macular oedema, epiretinal membrane and cataract in
      retinitis pigmentosa.
AB  - BACKGROUND/AIMS: To report the prevalence of treatable complications (cystoid
      macular oedema, CME; epiretinal membrane, ERM and cataract) in patients with
      retinitis pigmentosa (RP). METHODS: Consecutive patients with RP attending a
      tertiary eye clinic in 2012. Spectral domain-optical coherence tomography was
      used to determine presence of CME and ERM. Clinic records were reviewed to
      identify cataract and pseudophakia. Multivariable analyses adjusted for age,
      gender and other confounders. RESULTS: Data are presented for 338 eyes from 169
      patients. CME was present in 58.6% of patients and 50.9% of eyes and was
      bilateral in 73.7%. ERM, cataract and pseudophakia were present in 22.8%, 23.4%
      and 11.2% eyes, respectively. In multivariable analyses, CME was associated with
      younger age (OR 0.81, 95% CI 0.67 to 0.98) but not with gender. Patients with ERM
      and cataract/pseudophakia were less likely to also have CME (OR 0.19, 95%  CI
      0.09 to 0.40 and OR 0.37, 95%  CI 0.16 to 0.84, respectively). CME was most
      prevalent in patients with autosomal-dominant inheritance (71.4%), followed by
      autosomal recessive/sporadic inheritance (58.9%) and least likely in persons with
      X linked inheritance (12.5%, p<0.001). CONCLUSIONS: The prevalence of treatable
      RP complications is high and suggests it may be clinically beneficial to screen
      patients with RP to identify those who may benefit from current or future
      interventions.

PMID- 30291137
TI  - Outcomes of cataract surgery performed by non-physician cataract surgeons in
      remote North Cameroon.
AB  - OBJECTIVE: To report the outcomes of cataract surgery performed by non-physician
      cataract surgeons due to lack of ophthalmologists in remote areas of North
      Cameroon. DESIGN: Prospective cohort study. SETTING: The main centre of the non
      governmental organisation Ophtalmo Sans Frontieres in Lagdo. PARTICIPANTS AND
      INTERVENTIONS: Age-related cataract surgery performed between 28 November 2016
      and 17 May 2017. MAIN OUTCOMES MEASURES: The main outcome measure was presenting
      visual acuity (PVA) 1-4 weeks after surgery, classified according to the WHO as
      good (PVA >=6/18), borderline (PVA 6/60-6/18) and poor (PVA <6/60). The WHO
      definition of blindness (visual acuity <3/60) and severe visual acuity (visual
      acuity 3/60-6/60) was used to assess the proportion of patients with a change in
      WHO category. RESULTS: We included 474 eyes of 474 patients; the mean (SD) age
      was 63.9 (15) years (42.2% female). At 1-4 weeks after surgery, the surgical
      outcome was good for 170 patients (41.1%), borderline for 213 (51.5%) and poor
      for 31 (7.5%). In all, 224 patients (47.2%) had blindness or severe visual
      impairment before cataract surgery and 22 (5.3%) at 1-4 weeks after surgery. Poor
      visual outcome was associated with older age (p=0.018), preoperative blindness or
      severe impairment (p=0.012) and surgical complications (p=0.019). CONCLUSION:
      Blindness and severe visual impairment were significantly decreased in the early
      postoperative period. Poor outcomes were associated with older age, low
      preoperative binocular visual acuity and intraoperative complications. Non
      physician cataract surgeons may compensate for the lack of ophthalmologists in
      remote areas of low-income and middle-income countries.

PMID- 30291138
TI  - A critical period of susceptibility to sound in the sensory cells of cephalopod
      hatchlings.
AB  - The cephalopod statocyst and lateral line systems are sensory organs involved in
      orientation and balance. Lateral lines allow cephalopods to detect particle
      motion and are used for locating prey or predators in low light conditions. Here,
      we show the first analysis of damaged sensory epithelia in three species of
      cephalopod hatchlings (Sepia officinalis, Loligo vulgaris and Illex coindetii)
      after sound exposure. Our results indicate lesions in the statocyst sensory
      epithelia, similar to what was found in adult specimens. The novelty is that the
      severity of the lesions advanced more rapidly in hatchlings than in adult
      animals; i.e. the degree of lesions seen in hatchlings immediately after noise
      exposure would develop within 48 h in adults. This feature suggests a critical
      period of increased sensitivity to acoustic trauma in those species as has been
      described in developing mammalian cochlea and avian basilar papilla. The hair
      cells in the lateral lines of S. officinalis followed the same pattern of damage
      occurrence, while those of L. vulgaris and I. coindetii displayed a decreasing
      severity of damage after 24 h. These differences could be due to dissimilarities
      in size and life stages between the three species.

PMID- 30291139
TI  - Trends in the use of prenatal testing services for fetal aneuploidy in Ontario: a
      descriptive study.
AB  - BACKGROUND: In 2014, Ontario augmented its publicly funded multiple-marker
      screening program for prenatal aneuploidy by incorporating cell-free fetal DNA
      (cffDNA) analysis for high-risk pregnancies. We assessed trends in the use of
      multiple-marker screening, cffDNA screening and prenatal diagnostic testing
      before and after implementation of public funding. METHODS: We conducted a
      descriptive study based on data from the Better Outcomes Registry & Network
      (BORN) Ontario. The study population included all pregnant women in Ontario with
      a singleton pregnancy and an expected date of delivery between July 1, 2012, and
      Mar. 31, 2016, with pregnancy data captured in BORN. Pregnancy losses and
      terminations before 20 weeks' gestation not captured in BORN were excluded. We
      generated descriptive statistics to show trends and regional variations in use.
      RESULTS: The study sample included 534 210 singleton pregnancies. After cffDNA
      screening was funded for specific indications, uptake of multiple-marker
      screening increased slightly, from 66.5% to 68.1% (p < 0.001). Uptake of cffDNA
      screening among women with a positive multiple-marker screening result increased
      substantially, from 3.2% to 48.8% (p < 0.001). In contrast, the rate of prenatal
      diagnostic testing in this group decreased from 54.8% to 30.8% (p < 0.001).
      Although women aged 40 years or older are eligible for primary cffDNA screening,
      only a small decrease in the use of multiple-marker screening was observed in
      this group. The greatest use of cffDNA screening and greatest decline in prenatal
      diagnostic testing were seen in women with a level of risk for trisomy 21 of
      1:101-1:200 based on multiple-marker screening. INTERPRETATION: After public
      funding of cffDNA screening was implemented in Ontario, there was a significant
      increase in cffDNA screening and a significant decrease in prenatal diagnostic
      testing among women with a positive multiple-marker screening result. These
      changing patterns show the significant impact of public policy and funding
      decisions on women's choices regarding prenatal testing.

PMID- 30291140
TI  - Brexit: no deal would be "disaster" for patients in Northern Ireland, GP leader
      warns.

PMID- 30291141
TI  - Human DPP9 represses NLRP1 inflammasome and protects against auto-inflammatory
      diseases via both peptidase activity and FIIND domain binding.
AB  - The inflammasome is a critical molecular complex that activates IL-1 driven
      inflammation in response to pathogen- and danger-associated signals. Germline
      mutations in the inflammasome sensor, NLRP1 cause Mendelian systemic autoimmunity
      and skin cancer susceptibility, but its endogenous regulation remains less
      understood. Here we use a proteomics screen to uncover dipeptidyl dipeptidase,
      DPP9 as a novel interacting partner with human NLRP1 and a related inflammasome
      regulator, CARD8. DPP9 functions as an endogenous inhibitor of NLRP1 inflammasome
      in diverse primary cell types from human and mice. DPP8/9 inhibition via small
      molecule drugs and CRISPR/Cas9-mediated genetic deletion specifically activate
      human NLRP1 inflammasome, leading to ASC speck formation, pyroptotic cell death
      and secretion of cleaved IL-1beta. Mechanistically, DPP9 interacts with a unique
      auto-proteolytic domain (FIIND) found in NLRP1 and CARD8. This scaffolding
      function of DPP9 and its catalytic activity act synergistically to maintain NLRP1
      in its inactive state and repress downstream inflammasome activation. We further
      identified a single patient-derived germline missense mutation in NLRP1 FIIND
      domain that abrogates DPP9 binding, leading to inflammasome hyper-activation seen
      in the Mendelian auto-inflammatory disease AIADK. These results unite recent
      findings on the regulation of murine Nlrp1b by Dpp8/9 and uncover a new
      regulatory mechanism for the NLRP1 inflammasome in primary human cells. Our
      results further suggest that DPP9 could be a multi-functional inflammasome
      regulator involved in human auto-inflammatory diseases.

PMID- 30291142
TI  - Inducible microRNA-590-5p inhibits host antiviral response by targeting the
      soluble interleukin-6 (IL6) receptor.
AB  - MicroRNA (miR)-590-5p has been identified as an important regulator of some
      signaling pathways such as cell proliferation and tumorigenesis. However, little
      is known about its role during viral infection. Here, we report that miR-590-5p
      was significantly induced by various viruses and effectively potentiated virus
      replication in different viral infection systems. Furthermore, miR-590-5p
      substantially attenuated the virus-induced expression of type I and type III
      interferons (IFNs) and inflammatory cytokines, resulting in impaired downstream
      antiviral signaling. Interleukin-6 receptor (IL6R) was identified as a target of
      miR-590-5p. Interestingly, the role of miR-590-5p in virus-triggered signaling
      was abolished in IL6R knockout cells, and this could be rescued by restoring the
      expression of the soluble IL6R (sIL6R) but not the membrane-bound IL6R (mIL6R),
      suggesting that sIL6R is indispensable for miR-590-5p in modulating the host
      antiviral response. Furthermore, miR-590-5p down-regulated endogenous sIL6R and
      mIL6R expression through a translational repression mechanism. These findings
      thus uncover a previously uncharacterized role and the underlying mechanism of
      miR-590-5p in the innate immune response to viral infection.

PMID- 30291143
TI  - Mechanistic basis for the evolution of chalcone synthase catalytic cysteine
      reactivity in land plants.
AB  - Flavonoids are important polyphenolic natural products, ubiquitous in land
      plants, that play diverse functions in plants' survival in their ecological
      niches, including UV protection, pigmentation for attracting pollinators,
      symbiotic nitrogen fixation, and defense against herbivores. Chalcone synthase
      (CHS) catalyzes the first committed step in plant flavonoid biosynthesis and is
      highly conserved in all land plants. In several previously reported crystal
      structures of CHSs from flowering plants, the catalytic cysteine is oxidized to
      sulfinic acid, indicating enhanced nucleophilicity in this residue associated
      with its increased susceptibility to oxidation. In this study, we report a set of
      new crystal structures of CHSs representing all five major lineages of land
      plants (bryophytes, lycophytes, monilophytes, gymnosperms, and angiosperms),
      spanning 500 million years of evolution. We reveal that the structures of CHS
      from a lycophyte and a moss species preserve the catalytic cysteine in a reduced
      state, in contrast to the cysteine sulfinic acid seen in all euphyllophyte CHS
      structures. In vivo complementation, in vitro biochemical and mutagenesis
      analyses, and molecular dynamics simulations identified a set of residues that
      differ between basal-plant and euphyllophyte CHSs and modulate catalytic cysteine
      reactivity. We propose that the CHS active-site environment has evolved in
      euphyllophytes to further enhance the nucleophilicity of the catalytic cysteine
      since the divergence of euphyllophytes from other vascular plant lineages 400
      million years ago. These changes in CHS could have contributed to the
      diversification of flavonoid biosynthesis in euphyllophytes, which in turn
      contributed to their dominance in terrestrial ecosystems.

PMID- 30291144
TI  - A dominant dendrite phenotype caused by the disease-associated G253D mutation in
      doublecortin (DCX) is not due to its endocytosis defect.
AB  - Doublecortin (DCX[1]) is a protein needed for cortical development, and DCX
      mutations cause cortical malformations in humans. The microtubule-binding
      activity of DCX is well described and is important for its function, such as
      supporting neuronal migration and dendrite growth during development. Previous
      work showed that microtubule binding is not sufficient for DCX-mediated promotion
      of dendrite growth, and that domains in DCX's C-terminus are also required. The
      more C-terminal regions of DCX bind several other proteins, including the
      adhesion receptor neurofascin and clathrin adaptors. We recently identified a
      role for DCX in endocytosis of neurofascin. The disease-associated DCX-G253D
      mutant protein is known to be deficient in binding neurofascin, and we now asked
      if disruption of neurofascin endocytosis underlies the DCX-G253D-associated
      pathology. We first demonstrated that DCX functions in endocytosis as a complex
      with both the clathrin adaptor AP-2 and neurofascin: disrupting either clathrin
      adaptor binding (DCX-ALPA) or neurofascin binding (DCX-G253D) decreased
      neurofascin endocytosis in primary neurons. We then investigated a known function
      for DCX, namely, increasing dendrite growth in cultured neurons. Surprisingly, we
      found that the DCX-ALPA and DCX-G253D mutants yield distinct dendrite phenotypes.
      dnlike DCX-ALPA, DCX-G253D caused a dominant-negative dendrite growth phenotype.
      The endocytosis defect of DCX-G253D thus was separable from its detrimental
      effects on dendrite growth. We recently identified DCX-R59H as a dominant allele
      and can now classify DCX-G253D as a second DCX allele that acts dominantly to
      cause pathology, but does so via a different mechanism.

PMID- 30291145
TI  - Electrical Impedance Methods in Neuromuscular Assessment: An Overview.
AB  - Electrical impedance methods have been used as evaluation tools in biological and
      medical science for well over 100 years. However, only recently have these
      techniques been applied specifically to the evaluation of conditions affecting
      nerve and muscle. This specific application, termed electrical impedance
      myography (EIM), is finding wide application as it can provide a quantitative
      index of muscle condition that can assist with diagnosis, track disease
      progression, and assess the beneficial impact of therapy. Using noninvasive
      surface methods, EIM has been studied in a number of conditions ranging from
      amyotrophic lateral sclerosis to muscular dystrophy to disuse atrophy. Data
      support that the technique is sensitive to disease status and can offer the
      possibility of performing clinical trials with fewer subjects than would
      otherwise be possible. Recent advances in the field include improved approaches
      for using EIM as a "virtual biopsy" and the development of combined needle
      impedance-electromyography technology.

PMID- 30291146
TI  - Optogenetic Medicine: Synthetic Therapeutic Solutions Precision-Guided by Light.
AB  - Gene- and cell-based therapies are well recognized as central pillars of next
      generation medicine, but controllability remains a critical issue for clinical
      applications. In this context, optogenetics is opening up exciting new
      opportunities for precision-guided medicine by using illumination with light of
      appropriate intensity and wavelength as a trigger signal to achieve pinpoint
      spatiotemporal control of cellular activities, such as transgene expression. In
      this review, we highlight recent advances in optogenetics, focusing on devices
      for biomedical applications. We introduce the construction and applications of
      optogenetic-based biomedical tools to treat neurological diseases, diabetes,
      heart diseases, and cancer, as well as bioelectronic implants that combine light
      interfaced electronic devices and optogenetic systems into portable personalized
      precision bioelectronic medical tools. Optogenetics-based technology promises the
      capability to achieve traceless, remotely controlled precision dosing of an
      enormous range of therapeutic outputs. Finally, we discuss the prospects for
      optogenetic medicine, as well as some emerging challenges.

PMID- 30291147
TI  - Technobiology's Enabler: The Magnetoelectric Nanoparticle.
AB  - To enable patient- and disease-specific diagnostic and treatment at the
      intracellular level in real time, it is imperative to engineer a perfect way to
      locally stimulate selected individual neurons, navigate and dispense a cargo of
      biomolecules into damaged cells or image sites with relatively high efficacy and
      with adequate spatial and temporal resolutions. Significant progress has been
      made using biotechnology; especially with the development of bioinformatics,
      there are endless molecular databases to identify biomolecules to target almost
      any disease-specific biomarker. Conversely, the technobiology approach that
      exploits advanced engineering to control underlying molecular mechanisms to
      recover biosystem's energy states at the molecular level as well as at the level
      of the entire network of cells (i.e., the internet of the human body) is still in
      its early research stage. The recently developed magnetoelectric nanoparticles
      (MENPs) provide a tool to enable the unique capabilities of technobiology. Using
      exemplary studies that could potentially lead to future pinpoint treatment and
      prevention of cancer, neurodegenerative diseases, and HIV, this article discusses
      how MENPs could become a vital enabling tool of technobiology.

PMID- 30291148
TI  - Prostate Stem Cells and Cancer Stem Cells.
AB  - Stem/progenitor cells play central roles in processes of organogenesis and tissue
      maintenance, whereas cancer stem cells (CSCs) are thought to drive tumor
      malignancy. Here, we review recent progress in the identification and analysis of
      normal prostate stem/progenitor cells as well as putative CSCs in both
      genetically engineered mouse models as well as in human tissue. We also discuss
      studies that have investigated the cell type of origin for prostate cancer. In
      addition, we provide a critical assessment of methodologies used in stem cell
      analyses and outline directions for future research.

PMID- 30291149
TI  - Age-Related Hearing Loss.
AB  - Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the
      elderly. This progressive hearing impairment leads to social isolation and is
      also associated with comorbidities, such as frailty, falls, and late-onset
      depression. Moreover, there is a growing evidence linking it with cognitive
      decline and increased risk of dementia. Given the large social and welfare burden
      that results from ARHL, and because ARHL is potentially a modifiable risk factor
      for dementia, there is an urgent need for therapeutic interventions to ameliorate
      age-related auditory decline. However, a prerequisite for design of therapies is
      knowledge of the underlying molecular mechanisms. Currently, our understanding of
      ARHL is very limited. Here, we review recent findings from research into ARHL
      from both human and animal studies and discuss future prospects for advances in
      our understanding of genetic susceptibility, pathology, and potential therapeutic
      approaches in ARHL.

PMID- 30291150
TI  - Function and Dysfunction of TMC Channels in Inner Ear Hair Cells.
AB  - The TMC1 channel was identified as a protein essential for hearing in mouse and
      human, and recognized as one of a family of eight such proteins in mammals. The
      TMC family is part of a superfamily of seven branches, which includes the
      TMEM16s. Vertebrate hair cells express both TMC1 and TMC2. They are located at
      the tips of stereocilia and are required for hair cell mechanotransduction. TMC1
      assembles as a dimer and its similarity to the TMEM16s has enabled a predicted
      tertiary structure with an ion conduction pore in each subunit of the dimer.
      Cysteine mutagenesis of the pore supports the role of TMC1 and TMC2 as the core
      channel proteins of a larger mechanotransduction complex that includes PCDH15 and
      LHFPL5, and perhaps TMIE, CIB2 and others.

PMID- 30291152
TI  - "Fit notes" could become part of GP training, says deputy chief medical officer.

PMID- 30291151
TI  - An interview with Robb Krumlauf.
AB  - Robb Krumlauf is a developmental biologist who studies the Hox family of
      transcription factors, aiming to understand how these proteins regulate animal
      body plans. Robb, who is currently Scientific Director of the Stowers Institute
      for Medical Research, was recently awarded the 2018 SDB Edwin G. Conklin Award
      for his extraordinary contributions to the field of developmental biology and for
      his excellent mentoring skills. We met with Robb at this year's SDB Annual
      Meeting, where he was presented with the award, to find out more about his
      research, his career and his thoughts on mentorship.

PMID- 30291153
TI  - Protective effects of helmets on bicycle-related injuries in elderly individuals.
AB  - OBJECTIVE: The increasing frequency of bicycle-related injuries is due to the
      growing elderly population and their increasing physical activity. This study
      aimed to compare the protective effects of helmets on bicycle-related injuries in
      elderly individuals compared with those in younger adults. METHODS: Data from the
      Korean emergency department-based Injury In-depth Surveillance database from
      eight emergency departments during 2011-2016 were retrospectively analysed. The
      subjects sustained injuries while riding bicycles. Cases with unknown clinical
      outcomes were excluded. Covariates included mechanism, place and time of injury.
      The primary outcome was traumatic brain injury (TBI) incidence, and the secondary
      outcomes were in-hospital mortality and severe trauma. The effects of helmets on
      these outcomes were analysed and differences in effects were determined using
      logistic regression analysis. Subsequently, the differences in the effects of
      helmets use between age groups were examined by using interaction analysis
      RESULTS: Of 7181 adults, 1253 were aged >65 years. The injury incidents showed a
      bimodal pattern with peaks around ages 20 and 50 years. Meanwhile, the helmet
      wearing rate showed a unimodal pattern with its peak at age 35-40 years; it
      decreased consistently with age. By multivariate analysis, helmet-wearing was
      associated with a reduced TBI incidence (OR 0.76; 95% CI 0.57 to 0.99) and severe
      trauma (OR 0.78; 95%  CI 0.65 to 0.93). The effects of helmets increased in
      elderly individuals (TBI (p=0.022) and severe trauma (p=0.024)). CONCLUSION: The
      protective effects of helmets on bicycle-related injuries are greater for elderly
      individuals, thus reducing TBI incidence.

PMID- 30291154
TI  - Challenges of enforcing cell phone use while driving laws among police: a
      qualitative study.
AB  - BACKGROUND: Cell phone use while driving laws do not appear to be heavily
      enforced in the USA. This study seeks to gain law enforcements' perspective and
      learn potential barriers to cell phone law enforcement. METHODS: Qualitative
      interviews (ie, focus groups) were conducted with officers (N=19) from five West
      Virginia law enforcement agencies. The officers who participated were >18 years
      of age, sworn into their departments and employed in law enforcement for >1 year.
      Focus group sessions lasted 45-60 min and followed a standardised, pilot-tested
      script. These sessions were audio recorded and transcribed. Qualitative content
      analysis was employed among three researchers to determine themes surrounding
      enforcement. RESULTS: Four themes emerged including current culture, the legal
      system, the nature of police work and issues with prevention. Specific barriers
      to enforcement included cultural norms, lack of perceived support from
      courts/judges, different laws between states, the need for a general distracted
      driving law, unclear legislation, officers' habits and perceived risk, wanting to
      maintain a positive relationship with the public, not being able to see the
      driver (impediments of vehicle design, time of day), phones having multiple
      functions and not knowing what drivers are actually doing, risk of crashing
      during traffic stops and lack of resources. Prevention activities were debated,
      and most felt that technological advancements implemented by cell phone
      manufacturers may deter use. CONCLUSIONS: Numerous barriers to cell phone law
      enforcement exist. Legislation could be amended to facilitate enforcement.
      Prevention opportunities exist to deter cell phone use while driving.

PMID- 30291155
TI  - Injury prevention class exercise: three-pronged list making.
AB  - It is difficult to find classroom exercises that have been specifically designed
      for injury prevention students. The suggested list-making classroom exercise
      forces students to recognise and devise many policy and programmatic options over
      and above the ones that normally spring to mind. Most important, it helps give
      students a better understanding of what is meant by, and the potential usefulness
      of, the public health approach to injury prevention.

PMID- 30291156
TI  - A solution to Nature's haemoglobin knockout: a plasma-accessible carbonic
      anhydrase catalyses CO2 excretion in Antarctic icefish gills.
AB  - In all vertebrates studied to date, CO2 excretion depends on the enzyme carbonic
      anhydrase (CA) that catalyses the rapid conversion of HCO3 - to CO2 at the gas
      exchange organs. The largest pool of CA is present within red blood cells (RBCs)
      and, in some vertebrates, plasma-accessible CA (paCA) isoforms participate in CO2
      excretion. However, teleost fishes typically do not have paCA at the gills and
      CO2 excretion is reliant entirely on RBC CA - a strategy that is not possible in
      icefishes. As the result of a natural knockout, Antarctic icefishes
      (Channichthyidae) are the only known vertebrates that do not express haemoglobin
      (Hb) as adults, and largely lack RBCs in the circulation (haematocrit <1%).
      Previous work has indicated the presence of high levels of membrane-bound CA
      activity in the gills of icefishes, but without determining its cellular
      orientation. Thus, we hypothesised that icefishes express a membrane-bound CA
      isoform at the gill that is accessible to the blood plasma. The CA distribution
      was compared in the gills of two closely related notothenioid species, one with
      Hb and RBCs (Notothenia rossii) and one without (Champsocephalus gunnari).
      Molecular, biochemical and immunohistochemical markers indicate high levels of a
      Ca4 isoform in the gills of the icefish (but not the red-blooded N. rossii), in a
      plasma-accessible location that is consistent with a role in CO2 excretion. Thus,
      in the absence of RBC CA, the icefish gill could exclusively provide the
      catalytic activity necessary for CO2 excretion - a pathway that is unlike that of
      any other vertebrate.

PMID- 30291157
TI  - Hydrodynamics of linear acceleration in bluegill sunfish, Lepomis macrochirus.
AB  - In their natural habitat, fish rarely swim steadily. Instead they frequently
      accelerate and decelerate. Relatively little is known about how fish produce
      extra force for acceleration in routine swimming behavior. In this study, we
      examined the flow around bluegill sunfish Lepomis macrochirus during steady
      swimming and during forward acceleration, starting at a range of initial swimming
      speeds. We found that bluegill produce vortices with higher circulation during
      acceleration, indicating a higher force per tail beat, but they do not
      substantially redirect the force. We quantified the flow patterns using high
      speed video and particle image velocimetry and measured acceleration with small
      inertial measurement units attached to each fish. Even in steady tail beats, the
      fish accelerates slightly during each tail beat, and the magnitude of the
      acceleration varies. In steady tail beats, however, a high acceleration is
      followed by a lower acceleration or a deceleration, so that the swimming speed is
      maintained; in unsteady tail beats, the fish maintains the acceleration over
      several tail beats, so that the swimming speed increases. We can thus compare the
      wake and kinematics during single steady and unsteady tail beats that have the
      same peak acceleration. During unsteady tail beats when the fish accelerates
      forward for several tail beats, the wake vortex forces are much higher than those
      at the same acceleration during single tail beats in steady swimming. The fish
      also undulates its body at higher amplitude and frequency during unsteady tail
      beats. These kinematic changes likely increase the fluid dynamic added mass of
      the body, increasing the forces required to sustain acceleration over several
      tail beats. The high amplitude and high frequency movements are also likely
      required to generate the higher forces needed for acceleration. Thus, it appears
      that bluegill sunfish face a trade-off during acceleration: the body movements
      required for acceleration also make it harder to accelerate.

PMID- 30291158
TI  - Should I stay or should I go? The settlement-inducing protein complex guides
      barnacle settlement decisions.
AB  - Reproduction in barnacles relies on chemical cues that guide their gregarious
      settlement. These cues have been pinned down to several sources of settlement
      pheromones, one of which is a protein termed settlement-inducing protein complex
      (SIPC), a large glycoprotein acting as a pheromone to induce larval settlement
      and as an adhesive in surface exploration by the cyprids. Settlement assays in
      laboratory conditions with Amphibalanus (=Balanus) amphitrite cyprids in the
      presence of SIPC showed that cyprids exhibit settlement preference behaviour at
      lower concentrations of SIPC [half maximal effective concentration (EC50)=3.73
      nmol l-1] and settlement avoidance behaviour at higher concentrations (EC50=101
      nmol l-1). By using truncated fragments of SIPC in settlement assays, we identify
      that domains at the N-terminus of SIPC transduce settlement preference cues that
      mask the settlement avoidance cues transduced by domains at its C-terminus.
      Removing the N-terminal 600 amino acids from SIPC resulted in truncated fragments
      that transduced only settlement avoidance cues to the cyprids. From the sexual
      reproduction point of view, this bimodal response of barnacles to SIPC suggests
      that barnacles will settle gregariously when conspecific cues are sparse but will
      not settle if conspecific cues inform of overcrowding that will increase
      reproductive competition and diminish their reproductive chances.

PMID- 30291159
TI  - Hawkmoth flight in the unsteady wakes of flowers.
AB  - Flying animals maneuver and hover through environments where wind gusts and
      flower wakes produce unsteady flow. Although both flight maneuvers and
      aerodynamic mechanisms have been studied independently, little is known about how
      these interact in an environment where flow is already unsteady. Moths forage
      from flowers by hovering in the flower's wake. We investigated hawkmoths tracking
      a 3D-printed robotic flower in a wind tunnel. We visualized the flow in the wake
      and around the wings and compared tracking performance with previous experiments
      in a still-air flight chamber. As in still air, moths flying in the flower wake
      exhibit near-perfect tracking at the low frequencies at which natural flowers
      move. However, tracking in the flower wake results in a larger overshoot between
      2 and 5 Hz. System identification of flower tracking reveals that moths also
      display reduced-order dynamics in wind compared with still air. Smoke
      visualization of the flower wake shows that the dominant vortex shedding
      corresponds to the same frequency band as the increased overshoot. Despite these
      large effects on tracking dynamics in wind, the leading edge vortex (LEV) remains
      bound to the wing throughout the wingstroke and does not burst. The LEV also
      maintains the same qualitative structure seen in steady air. Persistence of a
      stable LEV during decreased flower tracking demonstrates the interplay between
      hovering and maneuvering.

PMID- 30291160
TI  - Substantial heat tolerance acclimation capacity in tropical thermophilic snails,
      but to what benefit?
AB  - The theory for thermal acclimation of ectotherms suggests that (1) heat tolerance
      is traded off for thermal acclimation in thermophilic species and that (2)
      plasticity is constrained in tropically distributed ectotherms, which commonly
      experience relatively thermally stable environments. We observed substantial heat
      tolerance plasticity in a test of this theory using tropical, thermophilic marine
      intertidal snails that inhabit extremely hot and highly variable thermal
      environments. The implication of these results is that plasticity selection is
      largely driven by habitat temperature conditions irrespective of basal heat
      tolerance or latitude. However, heat tolerance of field-fresh snails was
      comparable with that of laboratory warm-acclimated snails, suggesting that snails
      in the field may often be unable to improve heat hardening with further
      environmental warming. These findings suggest that field referencing is crucial
      to using laboratory-measured acclimation capacity when inferring climate warming
      vulnerability in ectotherms, and overall they question how well current thermal
      biology theory predicts the outcomes of global change in intertidal environments.

PMID- 30291162
TI  - Inhibition of cell fate repressors secures the differentiation of the touch
      receptor neurons of Caenorhabditis elegans.
AB  - Terminal differentiation generates the specialized features and functions that
      allow postmitotic cells to acquire their distinguishing characteristics. This
      process is thought to be controlled by transcription factors called 'terminal
      selectors' that directly activate a set of downstream effector genes. In
      Caenorhabditis elegans, the differentiation of both the mechanosensory touch
      receptor neurons (TRNs) and the multidendritic nociceptor FLP neurons uses the
      terminal selectors UNC-86 and MEC-3. The FLP neurons fail to activate TRN genes,
      however, because a complex of two transcriptional repressors (EGL-44/EGL-46)
      prevents their expression. Here, we show that the ZEB family transcriptional
      factor ZAG-1 promotes TRN differentiation not by activating TRN genes but by
      preventing the expression of EGL-44/EGL-46. As EGL-44/EGL-46 also inhibits the
      production of ZAG-1, these proteins form a bistable, negative-feedback loop that
      regulates the choice between the two neuronal fates.

PMID- 30291161
TI  - Kinetics of adult hematopoietic stem cell differentiation in vivo.
AB  - Adult hematopoiesis has been studied in terms of progenitor differentiation
      potentials, whereas its kinetics in vivo is poorly understood. We combined
      inducible lineage tracing of endogenous adult hematopoietic stem cells (HSCs)
      with flow cytometry and single-cell RNA sequencing to characterize early steps of
      hematopoietic differentiation in the steady-state. Labeled cells, comprising
      primarily long-term HSCs and some short-term HSCs, produced megakaryocytic
      lineage progeny within 1 wk in a process that required only two to three cell
      divisions. Erythroid and myeloid progeny emerged simultaneously by 2 wk and
      included a progenitor population with expression features of both lineages.
      Myeloid progenitors at this stage showed diversification into granulocytic,
      monocytic, and dendritic cell types, and rare intermediate cell states could be
      detected. In contrast, lymphoid differentiation was virtually absent within the
      first 3 wk of tracing. These results show that continuous differentiation of HSCs
      rapidly produces major hematopoietic lineages and cell types and reveal
      fundamental kinetic differences between megakaryocytic, erythroid, myeloid, and
      lymphoid differentiation.

PMID- 30291163
TI  - Fam46a regulates BMP-dependent pre-placodal ectoderm differentiation in Xenopus.
AB  - The pre-placodal ectoderm (PPE) is a specialized ectodermal region which gives
      rise to the sensory organs and other systems. The PPE is induced from the neural
      plate border during neurulation, but the molecular mechanism of PPE formation is
      not fully understood. In this study, we examined the role of a newly identified
      PPE gene, Fam46a, during embryogenesis. Fam46a contains a nucleoside triphosphate
      transferase domain, but its function in early development was previously unclear.
      We show that Fam46a is expressed in the PPE in Xenopus embryos, and Fam46a
      knockdown induces abnormalities in the eye formation and the body color. At the
      neurula stage, Fam46a upregulates the expression of PPE genes and inhibits neural
      crest formation. We also show that Fam46a physically interacts with Smad1/Smad4
      and positively regulates BMP signaling. From these results, we conclude that
      Fam46a is required for PPE formation via the positive regulation of BMP
      signaling. Our study provides a new mechanism of ectodermal patterning via cell
      autonomous regulation of BMP signaling in the PPE.

PMID- 30291165
TI  - Loss of CHD1 causes DNA repair defects and enhances prostate cancer therapeutic
      responsiveness.

PMID- 30291164
TI  - Distinct temporal requirements for Sonic hedgehog signaling in development of the
      tuberal hypothalamus.
AB  - Sonic hedgehog (Shh) plays well characterized roles in brain and spinal cord
      development, but its functions in the hypothalamus have been more difficult to
      elucidate owing to the complex neuroanatomy of this brain area. Here, we use fate
      mapping and conditional deletion models in mice to define requirements for
      dynamic Shh activity at distinct developmental stages in the tuberal
      hypothalamus, a brain region with important homeostatic functions. At early time
      points, Shh signaling regulates dorsoventral patterning, neurogenesis and the
      size of the ventral midline. Fate-mapping experiments demonstrate that Shh
      expressing and -responsive progenitors contribute to distinct neuronal subtypes,
      accounting for some of the cellular heterogeneity in tuberal hypothalamic nuclei.
      Conditional deletion of the hedgehog transducer smoothened (Smo), after
      dorsoventral patterning has been established, reveals that Shh signaling is
      necessary to maintain proliferation and progenitor identity during peak periods
      of hypothalamic neurogenesis. We also find that mosaic disruption of Smo causes a
      non-cell autonomous gain in Shh signaling activity in neighboring wild-type
      cells, suggesting a mechanism for the pathogenesis of hypothalamic hamartomas,
      benign tumors that form during hypothalamic development.

PMID- 30291166
TI  - IL-4 and IL-13 Guide Early Thymic Progenitors To Mature toward Dendritic Cells.
AB  - Recently we reported that IL-4 and IL-13 signaling in murine early thymic
      progenitors (ETPs) expressing the heteroreceptor (HR) comprising IL-4 receptor
      alpha (IL-4Ralpha) and IL-13 receptor alpha 1 (IL-13Ralpha1) activate STAT6 and
      inhibit ETP maturation potential toward T cells. In this study, we asked whether
      IL-4 and IL-13 signaling through the HR mobilizes other STAT molecules to shape
      ETP fate decision. The findings indicate that HR+ ETPs undergoing cytokine
      signaling display increased STAT1, but not STAT3, phosphorylation in addition to
      STAT6 activation. In parallel, the ETPs had a STAT1-dependent heightened
      expression of IRF-8, a transcription factor essential for development of
      CD8alpha+ dendritic cells (DCs). Interestingly, STAT1 phosphorylation and IRF-8
      upregulation, which are independent of STAT6 activation, guided ETP maturation
      toward myeloid cells with a CD8alpha+ DC phenotype. Furthermore, these CD8alpha+
      DCs display a thymic resident phenotype, as they did not express SIRPalpha, a
      molecule presumed to be involved in cell migration. These findings suggest that
      IL-4 and IL-13 cytokine-induced HR signaling provides a double-edged sword that
      simultaneously blocks T cell lineage potential but advances myeloid maturation
      that could impact T cell selection and central tolerance.

PMID- 30291168
TI  - Antecedents of Obesity Among Children Born Extremely Preterm.
AB  - BACKGROUND: Childhood obesity is a pervasive public health problem with risk
      factors such as maternal prepregnancy BMI and rapid infant weight gain. Although
      catch-up weight gain promotes more favorable neurodevelopment among infants born
      preterm, it is not clear whether faster weight gain early in life, or other
      correlates of preterm birth, are associated with later obesity in this
      population. METHODS: We used prospective data from the multicenter, observational
      Extremely Low Gestational Age Newborn Study. Among 1506 eligible individuals in
      the initial cohort, 1198 were eligible for follow-up at 10 years of age. We
      examined BMI in 871 children (58% of the cohort; 74% of survivors) and analyzed
      relationships between antecedents and overweight or obesity at 10 years of age. A
      time-oriented approach to multinomial multivariable regression enabled us to
      calculate odds of overweight and obesity associated with pre- and postnatal
      antecedents. RESULTS: Prepregnancy maternal BMI >=25 and top quartile infant
      weight gain in the first year were associated with increased risk of both
      overweight and obesity at 10 years of age. Single marital status was a risk
      factor for later child obesity and exposure to tobacco smoke was a risk factor
      for later child overweight. CONCLUSIONS: The risk profiles for overweight and
      obesity at 10 years of age among children born extremely preterm appear to be
      similar to the risk profiles of overweight and obesity among children born at
      term.

PMID- 30291169
TI  - Biobanding: A New Paradigm for Youth Sports and Training.

PMID- 30291167
TI  - Helminth-Induced Production of TGF-beta and Suppression of Graft-versus-Host
      Disease Is Dependent on IL-4 Production by Host Cells.
AB  - Helminths stimulate the secretion of Th2 cytokines, like IL-4, and suppress
      lethal graft-versus-host disease (GVHD) after bone marrow transplantation. This
      suppression depends on the production of immune-modulatory TGF-beta and is
      associated with TGF-beta-dependent in vivo expansion of Foxp3+ regulatory T cells
      (Treg). In vivo expansion of Tregs is under investigation for its potential as a
      therapy for GVHD. Nonetheless, the mechanism of induced and TGF-beta-dependent in
      vivo expansion of Tregs, in a Th2 polarized environment after helminth infection,
      is unknown. In this study, we show that helminth-induced IL-4 production by host
      cells is critical to the induction and maintenance of TGF-beta secretion, TGF
      beta-dependent expansion of Foxp3+ Tregs, and the suppression of GVHD. In mice
      with GVHD, the expanding donor Tregs express the Th2-driving transcription
      factor, GATA3, which is required for helminth-induced production of IL-4 and TGF
      beta. In contrast, TGF-beta is not necessary for GATA3 expression by Foxp3+ Tregs
      or by Foxp3- CD4 T cells. Various cell types of innate or adaptive immune
      compartments produce high quantities of IL-4 after helminth infection. As a
      result, IL-4-mediated suppression of GVHD does not require invariant NKT cells of
      the host, a cell type known to produce IL-4 and suppress GVHD in other models.
      Thus, TGF-beta generation, in a manner dependent on IL-4 secretion by host cells
      and GATA3 expression, constitutes a critical effector arm of helminthic immune
      modulation that promotes the in vivo expansion of Tregs and suppresses GVHD.

PMID- 30291170
TI  - The structure and evolution of eukaryotic chaperonin-containing TCP-1 and its
      mechanism that folds actin into a protein spring.
AB  - Actin is folded to its native state in eukaryotic cytosol by the sequential
      allosteric mechanism of the chaperonin-containing TCP-1 (CCT). The CCT machine is
      a double-ring ATPase built from eight related subunits, CCT1-CCT8. Non-native
      actin interacts with specific subunits and is annealed slowly through sequential
      binding and hydrolysis of ATP around and across the ring system. CCT releases a
      folded but soft ATP-G-actin monomer which is trapped 80 kJ/mol uphill on the
      folding energy surface by its ATP-Mg2+/Ca2+ clasp. The energy landscape can be re
      explored in the actin filament, F-actin, because ATP hydrolysis produces
      dehydrated and more compact ADP-actin monomers which, upon application of force
      and strain, are opened and closed like the elements of a spring. Actin-based
      myosin motor systems underpin a multitude of force generation processes in cells
      and muscles. We propose that the water surface of F-actin acts as a low-binding
      energy, directional waveguide which is recognized specifically by the myosin
      lever-arm domain before the system engages to form the tight-binding actomyosin
      complex. Such a water-mediated recognition process between actin and myosin would
      enable symmetry breaking through fast, low energy initial binding events. The
      origin of chaperonins and the subsequent emergence of the CCT-actin system in
      LECA (last eukaryotic common ancestor) point to the critical role of CCT in
      facilitating phagocytosis during early eukaryotic evolution and the transition
      from the bacterial world. The coupling of CCT-folding fluxes to the cell cycle,
      cell size control networks and cancer are discussed together with directions for
      further research.

PMID- 30291171
TI  - New tools for evaluating protein tyrosine sulfation and carbohydrate sulfation.
AB  - Sulfation is a common modification of extracelluar glycans and tyrosine residues
      on proteins, which is important in many signalling pathways and interactions.
      Existing methods for studying sulfotransferases, the enzymes that catalyse
      sulfation, are cumbersome and low-throughput. Recent studies published in the
      Biochemical Journal have repurposed established biochemical assays from the
      kinase field and applied them to the characterisation of sulfotransferases.
      Biochemical screening of a library of kinase inhibitors revealed that compounds
      that target RAF kinases may also be repurposed to inhibit sulfotransferases.
      Together with the available structures of sulfotransferases, these studies open
      the door to the development of chemical tools to probe the biological functions
      of these important enzymes.

PMID- 30291172
TI  - Physicochemical Solubility of and Biological Sensitivity to Long-Chain Alcohols
      Determine the Cutoff Chain Length in Biological Activity.
AB  - The cutoff phenomenon associated with the effectiveness of long-chain alcohols in
      the induction of anesthesia is also observed for various antimicrobial
      activities, although the mechanism has remained unknown for over eight decades.
      The minimum inhibitory concentrations at 25 degrees C for budding yeast growth
      exponentially decreased with increasing chain length of n-alcohols (C2-C12),
      whereas alcohols >=C13 lost the inhibitory effect. Thus, growth inhibition by n
      alcohols obeys the Meyer-Overton correlation up to C12 and exhibits a cutoff
      phenomenon. The densities of n-alcohols are low, and the melting point and
      hydrophobicity increase with chain length. C13 and C14 inhibited yeast growth at
      39.8 degrees C, above their melting points. Alcohols <=C14 inhibited thermophilic
      bacterial growth at 50 degrees C, whereas C16 inhibited it at 67.5 degrees C,
      above their melting points. Thus, the high melting points of long-chain alcohols
      contribute to the cutoff phenomenon. C14 did not effectively inhibit yeast growth
      in a static culture at 39.8 degrees C, in contrast to a shaking culture, in which
      the low density-dependent concentration gradient was eliminated. The duration of
      the transient growth inhibition of yeast by C12 was prolonged by sonication,
      which prevented hydrophobic aggregation. Therefore, a nonuniform distribution
      owing to low density and high hydrophobicity contributes to the cutoff. C14
      inhibited the growth at 25 degrees C of the pdr1,3,5 mutant, defective in
      multidrug efflux pumps, whereas C12 did not inhibit the growth of yeast
      overexpressing PDR5, indicating that the sensitivity to long-chain alcohols
      contributed to the cutoff. A balance between the physicochemical solubility of
      and the biological sensitivity to long-chain alcohols determines the cutoff chain
      length.

PMID- 30291173
TI  - Safinamide Modulates Striatal Glutamatergic Signaling in a Rat Model of Levodopa
      Induced Dyskinesia.
AB  - Safinamide (Xadago) is a novel dual-mechanism drug that has been approved in the
      European Union and United States as add-on treatment to levodopa in Parkinson's
      disease therapy. In addition to its selective and reversible monoamine oxidase B
      inhibition, safinamide through use-dependent sodium channel blockade reduces
      overactive glutamatergic transmission in basal ganglia, which is believed to
      contribute to motor symptoms and complications including levodopa-induced
      dyskinesia (LID). The present study investigated the effects of safinamide on the
      development of LID in 6-hydroxydopamine (6-OHDA)-lesioned rats, evaluating
      behavioral, molecular, and neurochemical parameters associated with LID
      appearance. 6-OHDA-lesioned rats were treated with saline, levodopa (6 mg/kg), or
      levodopa plus safinamide (15 mg/kg) for 21 days. Abnormal involuntary movements,
      motor performance, molecular composition of the striatal glutamatergic synapse,
      glutamate, and GABA release were analyzed. In the striatum, safinamide prevented
      the rearrangement of the subunit composition of N-methyl-d-aspartate receptors
      and the levodopa-induced increase of glutamate release associated with dyskinesia
      without affecting the levodopa-stimulated motor performance and dyskinesia.
      Overall, these findings suggest that the striatal glutamate-modulating component
      of safinamide's activity may contribute to its clinical effects, where its long
      term use as levodopa add-on therapy significantly improves motor function and
      "on" time without troublesome dyskinesia.

PMID- 30291174
TI  - Celecoxib Treatment Improves Neurologic Deficit and Reduces Selective Neuronal
      Loss and Glial Response in Rats after Transient Middle Cerebral Artery Occlusion.
AB  - Areas of selective neuronal loss (SNL) represent the first morphologic signs of
      damage in the penumbra region and are considered putative targets for ischemic
      stroke therapy. We performed a novel assessment of measuring the effects of the
      anti-inflammatory agent celecoxib by analyzing simultaneously the different
      neural populations (neurons, astrocytes, and microglia cells) in SNL and non-SNL
      areas. Rats were subjected to 1 hour of middle cerebral artery occlusion (MCAO)
      and treated with celecoxib 1 and 24 hours after ischemia. Infarct volume
      measurements and triple immunostaining of neurons (neuronal nuclear antigen),
      microglia (ionized calcium-binding adaptor molecule 1), and astroglia were
      performed after 12 and 48 hours of reperfusion. Motor response was tested by
      standard behavioral assays at 3, 12, 24, and 48 hours. Confocal analysis revealed
      that the percentage of SNL areas, microglia densities, and glial activation
      increased at 48 hours of reperfusion. Celecoxib treatment improved the neurologic
      deficit, reduced the infarct volume by 50% after 48 hours of reperfusion, and
      resulted in a reduced percentage of SNL areas and microglia and astroglia
      reactivity after 48 hours of reperfusion. This study proves, for the first time,
      that celecoxib presents postischemic neuroprotective effects in a transient MCAO
      model, prevents or delays the presence of SNL areas, and reduces glial
      activation.

PMID- 30291176
TI  - Withdrawal: Nrf2/p62 signaling in apoptosis resistance and its role in cadmium
      induced carcinogenesis.

PMID- 30291175
TI  - Engineering Artificial MicroRNAs for Multiplex Gene Silencing and Simplified
      Transgenic Screen.
AB  - Artificial microRNA (amiRNA) technology offers reversible and flexible gene
      inactivation and complements genome-editing technologies. However, obtaining
      transgenic plants with maximal gene silencing remains a major technical challenge
      in current amiRNA applications. Here, we incorporated an empirically determined
      feature of effective amiRNAs to the amiRNA design and in silico generated a
      database containing 533,429 gene-specific amiRNAs for silencing 27,136 genes in
      Arabidopsis (Arabidopsis thaliana), with a genome coverage of 98.87%. In both
      single-gene and multiple-gene silencing, we observed an overall improvement in
      performance by amiRNAs designed using our strategy in Arabidopsis protoplasts and
      transgenic plants. In addition, the endogenous tRNA-processing system was used to
      generate multiple amiRNAs from tRNA-pre-amiRNA tandem repeats for multiplex gene
      silencing. An intronic amiRNA-producing fluorescent reporter was explored as a
      visual screening strategy for transgenic Arabidopsis and rice (Oryza sativa)
      plants with maximal whole-plant or cell type-specific gene silencing. These
      improvements enable the amiRNA technology to be a functional gene knockout tool
      for basic and applied plant research.

PMID- 30291177
TI  - Withdrawal: Antioncogenic and oncogenic properties of Nrf2 in arsenic-induced
      carcinogenesis.

PMID- 30291178
TI  - Withdrawal: Nuclear factor erythroid 2-related factor 2 enhances carcinogenesis
      by suppressing apoptosis and promoting autophagy in nickel-transformed cells.

PMID- 30291179
TI  - Framing the challenges of artificial intelligence in medicine.

PMID- 30291180
TI  - Application of electronic trigger tools to identify targets for improving
      diagnostic safety.
AB  - Progress in reducing diagnostic errors remains slow partly due to poorly defined
      methods to identify errors, high-risk situations, and adverse events. Electronic
      trigger (e-trigger) tools, which mine vast amounts of patient data to identify
      signals indicative of a likely error or adverse event, offer a promising method
      to efficiently identify errors. The increasing amounts of longitudinal electronic
      data and maturing data warehousing techniques and infrastructure offer an
      unprecedented opportunity to implement new types of e-trigger tools that use
      algorithms to identify risks and events related to the diagnostic process. We
      present a knowledge discovery framework, the Safer Dx Trigger Tools Framework,
      that enables health systems to develop and implement e-trigger tools to identify
      and measure diagnostic errors using comprehensive electronic health record (EHR)
      data. Safer Dx e-trigger tools detect potential diagnostic events, allowing
      health systems to monitor event rates, study contributory factors and identify
      targets for improving diagnostic safety. In addition to promoting organisational
      learning, some e-triggers can monitor data prospectively and help identify
      patients at high-risk for a future adverse event, enabling clinicians, patients
      or safety personnel to take preventive actions proactively. Successful
      application of electronic algorithms requires health systems to invest in
      clinical informaticists, information technology professionals, patient safety
      professionals and clinicians, all of who work closely together to overcome
      development and implementation challenges. We outline key future research,
      including advances in natural language processing and machine learning, needed to
      improve effectiveness of e-triggers. Integrating diagnostic safety e-triggers in
      institutional patient safety strategies can accelerate progress in reducing
      preventable harm from diagnostic errors.

PMID- 30291181
TI  - Virtual outpatient clinic as an alternative to an actual clinic visit after
      surgical discharge: a randomised controlled trial.
AB  - BACKGROUND: It is standard practice to review all patients following discharge at
      a follow-up clinic but demands on all health services outweigh resources and
      unnecessary review appointments may delay or deny access to patients with greater
      needs. AIMS: This randomised trial aimed to establish whether a virtual
      outpatient clinic (VOPC) was an acceptable alternative to an actual outpatient
      clinic (OPC) attendance for a broad range of general surgical patients following
      a hospital admission. PATIENTS AND METHODS: All patients admitted under one
      general surgical service over the study period were assessed. If eligible for
      inclusion the rationale, randomisation and follow-up methods were explained,
      consent was sought and patients randomised to receive either a VOPC or an OPC
      appointment. RESULTS: Two-hundred and nine patients consented to study inclusion,
      of which 98/107 (91.6%) in the VOPC group and 83/102 (81.4%) in the OPC group
      were successfully contacted. Only 6 patients in the OPC group and 10 in the VOPC
      group reported ongoing issues. A further follow-up indicated 78 of 82 (95%) VOPC
      patients were very happy with their overall experience compared with 34/61 (56%)
      in the actual OPC group (p<0.001). A significant proportion of both cohorts-68/82
      (83%) in VOPC group and 41/61 (67%) in OPC group (p = 0.029)-preferred a VOPC
      appointment as their future follow-up of choice. CONCLUSIONS: The majority of
      patients discharged from a surgical service could be better followed up by a
      virtual clinic with a significant proportion of patients reporting a preference
      for and a greater satisfaction with such a service.

PMID- 30291182
TI  - Clinical correlates of quantitative EEG in Parkinson disease: A systematic
      review.
AB  - OBJECTIVE: To assess the relevance of quantitative EEG (qEEG) measures as
      outcomes of disease severity and progression in Parkinson disease (PD). METHODS:
      Main databases were systematically searched (January 2018) for studies of
      sufficient methodologic quality that examined correlations between clinical
      symptoms of idiopathic PD and cortical (surface) qEEG metrics. RESULTS: Thirty
      six out of 605 identified studied were included. Results were classified into 4
      domains: cognition (23 studies), motor function (13 studies), responsiveness to
      interventions (7 studies), and other (10 studies). In cross-sectional studies,
      EEG slowing correlated with global cognitive impairment and with diffuse
      deterioration in other domains. In longitudinal studies, decreased dominant
      frequency and increased theta power, reflecting EEG slowing, were biomarkers of
      cognitive deterioration at an individual level. Results on motor dysfunction and
      treatment yielded contrasting findings. Studies on functional connectivity at an
      individual level and longitudinal studies on other domains or on connectivity
      measures were lacking. CONCLUSION: qEEG measures reflecting EEG slowing,
      particularly decreased dominant frequency and increased theta power, correlate
      with cognitive impairment and predict future cognitive deterioration. qEEG could
      provide reliable and widely available biomarkers for nonmotor disease severity
      and progression in PD, potentially promoting early diagnosis of nonmotor symptoms
      and an objective monitoring of progression. More studies are needed to clarify
      the role of functional connectivity and network analyses.

PMID- 30291183
TI  - CSF sAPPbeta, YKL-40, and NfL along the ALS-FTD spectrum.
AB  - OBJECTIVE: To investigate the clinical utility of 3 CSF biomarkers along the
      clinical spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal
      dementia (FTD). METHODS: We analyzed 3 CSF biomarkers: the soluble beta-fragment
      of amyloid precursor protein (sAPPbeta), YKL-40, and neurofilament light (NfL) in
      FTD (n = 86), ALS (n = 38), and a group of age-matched cognitively normal
      controls (n = 49). Participants with FTD with a CSF profile of Alzheimer disease
      were excluded. We compared cross-sectional biomarker levels between groups,
      studied their correlation with cognitive and functional scales (global cognitive
      z score, frontotemporal lobar degeneration Clinical Dementia Rating, revised ALS
      Functional Rating Scale, and ALS progression rate), survival, and cortical
      thickness. RESULTS: We found increased levels of YKL-40 and decreased levels of
      sAPPbeta in both FTD and ALS groups compared to controls. The lowest sAPPbeta
      levels and sAPPbeta/YKL-40 ratio were found in the FTD group. In FTD, sAPPbeta
      and the sAPPbeta/YKL-40 ratio correlated with the disease severity. In the whole
      ALS-FTD spectrum, NfL levels and the NfL:sAPPbeta ratio correlated with global
      cognitive performance (r = -0.41, p < 0.001 and r = -0.44, p < 0.001,
      respectively). In the ALS group, YKL-40 correlated with disease progression rate
      (r = 0.51, p = 0.001) and was independently associated with shorter survival. In
      both FTD and ALS groups, the sAPPbeta/YKL-40 ratio showed a positive correlation
      with cortical thickness in frontotemporal regions. CONCLUSIONS: sAPPbeta, YKL-40,
      and NfL could represent valuable tools for the staging and prognosis of patients
      within the ALS-FTD clinical spectrum. CLASSIFICATION OF EVIDENCE: This study
      provides Class III evidence that CSF levels of sAPPbeta, YKL-40, and NfL are
      useful to assess frontotemporal neurodegeneration and the progression rate in the
      ALS-FTD continuum.

PMID- 30291184
TI  - Evidence of mild founder LMOD3 mutations causing nemaline myopathy 10 in Germany
      and Austria.
AB  - OBJECTIVE: To expand the clinical and genetic spectrum of nemaline myopathy 10 by
      a series of Austrian and German patients with a milder disease course and
      missense mutations in LMOD3. METHODS: We characterized the clinical features and
      the genetic status of 4 unrelated adolescent or adult patients with nemaline
      myopathy. RESULTS: The 4 patients showed a relatively mild disease course. They
      all have survived into adulthood, 3 of 4 have remained ambulatory, and all showed
      marked facial weakness. Muscle biopsy specimens gave evidence of nemaline bodies.
      All patients were unrelated but originated from Austria (Tyrol and Upper Austria)
      and Southern Germany (Bavaria). All patients carried the missense variant
      c.1648C>T, p.(Leu550Phe) in the LMOD3 gene, either on both alleles or in trans
      with another missense variant (c.1004A>G, p.Gln335Arg). Both variants were not
      reported previously. CONCLUSIONS: In 2014, a severe form of congenital nemaline
      myopathy caused by disrupting mutations in LMOD3 was identified and denoted as
      NEM10. Unlike the previously reported patients, who had a severe clinical picture
      with a substantial risk of early death, our patients showed a relatively mild
      disease course. As the missense variant c.1648C>T is located further downstream
      compared to all previously published LMOD3 mutations, it might be associated with
      higher protein expression compared to the reported loss-of-function mutations.
      The apparent clusters of 2 mild mutations in Germany and Austria in 4 unrelated
      families may be explained by a founder effect.

PMID- 30291185
TI  - Congenital myasthenic syndromes in adult neurology clinic: A long road to
      diagnosis and therapy.
AB  - OBJECTIVE: To investigate the diagnostic challenges of congenital myasthenic
      syndromes (CMS) in adult neuromuscular practice. METHODS: We searched the Mayo
      Clinic database for patients with CMS diagnosed in adulthood in the neuromuscular
      clinic between 2000 and 2016. Clinical, laboratory, and electrodiagnostic data
      were reviewed. RESULTS: We identified 34 patients with CMS, 30 of whom had a
      molecular diagnosis (14 DOK7, 6 RAPSN, 2 LRP4, 2 COLQ, 2 slow-channel syndrome, 1
      primary acetylcholine receptor deficiency, 1 AGRN, 1 GFPT1, and 1 SCN4A).
      Ophthalmoparesis was often mild and present in 13 patients. Predominant limb
      girdle weakness occurred in 19 patients. Two patients had only ptosis. Age at
      onset ranged from birth to 39 years (median 5 years). The median time from onset
      to diagnosis was 26 years (range 4-56 years). Thirteen patients had affected
      family members. Fatigable weakness was present when examined. Creatine kinase was
      elevated in 4 of 23 patients (range 1.2-4.2 times the upper limit of normal).
      Repetitive nerve stimulation revealed a decrement in 30 patients. Thirty-two
      patients were previously misdiagnosed with seronegative myasthenia gravis (n =
      16), muscle diseases (n = 15), weakness of undetermined cause (n = 8), and others
      (n = 4). Fifteen patients received immunotherapy or thymectomy without benefits.
      Fourteen of the 25 patients receiving pyridostigmine did not improve or worsen.
      CONCLUSION: Misdiagnosis occurred in 94% of the adult patients with CMS and
      causes a median diagnostic delay of nearly 3 decades from symptom onset.
      Seronegative myasthenia gravis and muscle diseases were the 2 most common
      misdiagnoses, which led to treatment delay and unnecessary exposure to
      immunotherapy, thymectomy, or muscle biopsy.

PMID- 30291186
TI  - Middle cerebral artery geometric features are associated with plaque distribution
      and stroke.
AB  - OBJECTIVE: We aimed to investigate the geometric features of the middle cerebral
      artery (MCA) and their relevance to plaque distribution and ischemic stroke.
      METHODS: We reviewed our institutional vessel wall imaging database. Patients
      with symptomatic MCA atherosclerosis, asymptomatic MCA atherosclerosis, or
      without MCA atherosclerosis were included. The MCA geometric features, including
      M1 segment shape and M1 curve orientation, were defined on magnetic resonance
      angiography. Plaque distribution and other plaque parameters were identified on
      vessel wall imaging. The association among MCA geometric features, plaque
      distribution, and ischemic stroke were analyzed. RESULTS: A total of 977 MCAs
      were analyzed (87 atherosclerotic symptomatic MCAs, 459 atherosclerotic
      asymptomatic MCAs, and 431 plaque-free MCAs). Overall, curved M1 segments were
      the predominant shape across all groups. In 91.1% of curved atherosclerotic MCAs,
      the plaque involved the inner wall of the curve. Plaque not involving the inner
      wall was shorter (p < 0.0001) and thinner (p = 0.005) compared to plaque
      involving the inner wall. Inferior plaque was observed in 39.9% of inferior
      oriented M1 curves compared to 21.7% in non-inferior-oriented M1 curves (p <
      0.0001). The absence of an inferior-oriented M1 curve (odds ratio 0.45, 95%
      confidence interval 0.27-0.77) and presence of superior plaque (odds ratio 2.67,
      95% confidence interval 1.52-4.67) were independently associated with stroke
      after adjusting for plaque length and thickness, degree of stenosis, and
      remodeling ratio. CONCLUSIONS: MCA geometric features are associated with plaque
      distribution and stroke. Our findings provide insight into the vascular
      pathophysiology of MCA atherosclerosis.

PMID- 30291187
TI  - Outcomes after ischemic stroke caused by intracranial atherosclerosis vs
      dissection.
AB  - OBJECTIVE: To compare the outcomes between patients with nontraumatic
      intracranial arterial dissection (ICAD) and intracranial atherosclerotic stenosis
      (ICAS) using high-resolution MRI (HR-MRI). METHODS: We conducted a prospective
      study using HR-MRI in patients with acute symptomatic cerebrovascular disease due
      to intracranial occlusive disease and no dissection on luminal images. Patients
      were followed-up for 27.9 +/- 19.3 months. We compared the functional outcome,
      recurrence, and changes in vascular status between patients with ICAD (dissection
      and no plaque on HR-MRI) and ICAS (atherosclerosis plaque on HR-MRI). RESULTS: We
      included 312 patients (mean age, 59.0 +/- 14.2 years; men, 58.3%), of whom 113
      had ICAD and 199 had ICAS. The functional outcome (as measured by modified Rankin
      Scale score) on the 90th day after symptom onset was not different between the
      groups, after adjusted for other factors (p = 0.095). However, recurrent ischemic
      cerebrovascular disease on the relevant vascular territory was lower in the ICAD
      group (7 patients, 6.2%) than in the ICAS group (37 patients, 18.6%). ICAD was a
      significant independent determinant of disease recurrence (hazard ratio, 0.43;
      95% confidence interval, 0.19-0.98). Improvement in vascular stenosis on follow
      up vascular studies was more frequently observed in ICAD (50.7%) than in ICAS
      (11.6%). ICAD was an independent determinant of vascular improvement (odds ratio,
      7.94; 95% confidence interval, 3.32-19.01). CONCLUSION: Considering the high
      prevalence of ICAD in the patients with presumed ICAS and the differential
      outcomes between ICAD and ICAS, HR-MRI may be a useful diagnostic tool in this
      population.

PMID- 30291189
TI  - Glucose metabolism mediates disease tolerance in cerebral malaria.
AB  - Sickness behaviors are a conserved set of stereotypic responses to inflammatory
      diseases. We recently demonstrated that interfering with inflammation-induced
      anorexia led to metabolic changes that had profound effects on survival of acute
      inflammatory conditions. We found that different inflammatory states needed to be
      coordinated with corresponding metabolic programs to actuate tissue-protective
      mechanisms. Survival of viral inflammation required intact glucose utilization
      pathways, whereas survival of bacterial inflammation required alternative fuel
      substrates and ketogenic programs. We thus hypothesized that organismal
      metabolism would be important in other classes of infectious inflammation and
      sought to understand its role in the prototypic parasitic disease malaria.
      Utilizing the cerebral malaria model, Plasmodium berghei ANKA (PbA) infection in
      C57BL/6J male mice, we unexpectedly found that inhibition of glycolysis using 2
      deoxy glucose (2DG) conferred protection from cerebral malaria. Unlike vehicle
      treated animals, 2DG-treated animals did not develop cerebral malaria and
      survived until ultimately succumbing to fatal anemia. We did not find any
      differences in parasitemia or pathogen load in affected tissues. There were no
      differences in the kinetics of anemia. We also did not detect differences in
      immune infiltration in the brain or in blood-brain barrier permeability. Rather,
      on pathological analyses performed on the entire brain, we found that 2DG
      prevented the formation of thrombi and thrombotic complications. Using
      thromboelastography (TEG), we found that 2DG-treated animals formed clots that
      were significantly less strong and stable. Together, these data suggest that
      glucose metabolism is involved in inflammation-induced hemostasis and provide a
      potential therapeutic target in treatment of cerebral malaria.

PMID- 30291190
TI  - Verifying Larche-Cahn elasticity, a milestone of 20th-century thermodynamics.
AB  - Many materials phenomena are governed by the interaction between chemistry and
      mechanics. However, it was only in the second half of the 20th century that the
      theory of open system elasticity by Francis Larche and John W. Cahn concatenated
      the fields of solid mechanics and alloy chemistry. As the theory's central
      materials descriptors, the open system elastic parameters describe how solids
      deform under stress when solute can rearrange at equilibrium while the chemical
      potential is held constant. Here, we report experiments verifying the predictions
      for these parameters. We study the elasticity of nanoporous Pd-H and Pd-Au-H
      during load cycles imposed by a dynamic mechanical analyzer. Short diffusion
      paths afford fast equilibration of H in the local strain gradients that carry the
      macroscopic elastic deformation. The experiment is in excellent agreement with
      the theory, confirming a central prediction of one of the key contributions to
      20th-century thermodynamics.

PMID- 30291188
TI  - Quantitative and functional posttranslational modification proteomics reveals
      that TREPH1 plays a role in plant touch-delayed bolting.
AB  - Environmental mechanical forces, such as wind and touch, trigger gene-expression
      regulation and developmental changes, called "thigmomorphogenesis," in plants,
      demonstrating the ability of plants to perceive such stimuli. In Arabidopsis, a
      major thigmomorphogenetic response is delayed bolting, i.e., emergence of the
      flowering stem. The signaling components responsible for mechanotransduction of
      the touch response are largely unknown. Here, we performed a high-throughput
      SILIA (stable isotope labeling in Arabidopsis)-based quantitative
      phosphoproteomics analysis to profile changes in protein phosphorylation
      resulting from 40 seconds of force stimulation in Arabidopsis thaliana Of the 24
      touch-responsive phosphopeptides identified, many were derived from kinases,
      phosphatases, cytoskeleton proteins, membrane proteins, and ion transporters. In
      addition, the previously uncharacterized protein TOUCH-REGULATED PHOSPHOPROTEIN1
      (TREPH1) became rapidly phosphorylated in touch-stimulated plants, as confirmed
      by immunoblots. TREPH1 fractionates as a soluble protein and is shown to be
      required for the touch-induced delay of bolting and gene-expression changes.
      Furthermore, a nonphosphorylatable site-specific isoform of TREPH1 (S625A) failed
      to restore touch-induced flowering delay of treph1-1, indicating the necessity of
      S625 for TREPH1 function and providing evidence consistent with the possible
      functional relevance of the touch-regulated TREPH1 phosphorylation. Taken
      together, these findings identify a phosphoprotein player in Arabidopsis
      thigmomorphogenesis regulation and provide evidence that TREPH1 and its touch
      induced phosphorylation may play a role in touch-induced bolting delay, a major
      component of thigmomorphogenesis.

PMID- 30291191
TI  - Reducing dynamin 2 (DNM2) rescues DNM2-related dominant centronuclear myopathy.
AB  - Centronuclear myopathies (CNM) are a group of severe muscle diseases for which no
      effective therapy is currently available. We have previously shown that reduction
      of the large GTPase DNM2 in a mouse model of the X-linked form, due to loss of
      myotubularin phosphatase MTM1, prevents the development of the skeletal muscle
      pathophysiology. As DNM2 is mutated in autosomal dominant forms, here we tested
      whether DNM2 reduction can rescue DNM2-related CNM in a knock-in mouse harboring
      the p.R465W mutation (Dnm2 RW/+) and displaying a mild CNM phenotype similar to
      patients with the same mutation. A single intramuscular injection of adeno
      associated virus-shRNA targeting Dnm2 resulted in reduction in protein levels 5
      wk post injection, with a corresponding improvement in muscle mass and fiber size
      distribution, as well as an improvement in histopathological CNM features. To
      establish a systemic treatment, weekly i.p. injections of antisense
      oligonucleotides targeting Dnm2 were administered to Dnm2 RW/+mice for 5 wk.
      While muscle mass, histopathology, and muscle ultrastructure were perturbed in
      Dnm2 RW/+mice compared with wild-type mice, these features were indistinguishable
      from wild-type mice after reducing DNM2. Therefore, DNM2 knockdown via two
      different strategies can efficiently correct the myopathy due to DNM2 mutations,
      and it provides a common therapeutic strategy for several forms of centronuclear
      myopathy. Furthermore, we provide an example of treating a dominant disease by
      targeting both alleles, suggesting that this strategy may be applied to other
      dominant diseases.

PMID- 30291192
TI  - Dosimetry of Lu-177 PSMA-617 in metastatic castration-resistant prostate cancer:
      correlations between pre-therapeutic imaging and "whole body" tumor dosimetry
      with treatment outcomes.
AB  - 177Lu-PSMA-617 enables targeted delivery of beta-particle radiation to prostate
      cancer. We determined its radiation dosimetry and relationships to pre
      therapeutic imaging and outcomes. METHODS: 30 patients with prostate cancer
      receiving 177Lu-PSMA-617 within a prospective clinical trial
      (ACTRN12615000912583) were studied. Screening 68Ga-PSMA-11 PET-CT demonstrated
      high PSMA-expression in all patients. Following therapy patients underwent
      quantitative SPECT-CT at 4, 24 and 96 hours. Pharmacokinetic uptake and clearance
      at a voxel level was calculated and translated into absorbed dose using voxel S
      values. Volumes-of-interest were drawn on normal tissues and tumor to assess
      radiation dose and a 'whole-body' tumor dose was also defined. Correlations
      between PSMA PET-CT parameters, dosimetry and biochemical and therapeutic
      response were analyzed to identify relationships between absorbed dose, tumor
      burden, and patient physiology. RESULTS: Mean absorbed dose to kidneys,
      submandibular and parotid glands, liver, spleen and bone marrow were 0.39, 0.44,
      0.58, 0.1, 0.06 and 0.11 Gy/MBq, respectively. Median 'whole body' tumor absorbed
      dose was 11.55 Gy and correlated with PSA response at 12 weeks. A median dose of
      14.1 Gy was observed in patients achieving PSA>=50% decline vs. 9.6 Gy for those
      achieving PSA<50% (p<0.01). Of 11 patients receiving a tumor dose less than 10 Gy
      only one achieved a PSA response >=50%. On screening PSMA PET, "whole body" tumor
      SUVmean correlated with mean absorbed dose (r=0.62) and SUVmax of the parotids
      also correlated with absorbed dose (r=0.67). There was an inverse correlation
      between tumor volume and mean dose to the parotids (r=-0.41) and kidneys (r=
      0.43). Mean parotid dose was also reduced with increasing body mass (r=-0.41) and
      body surface area (r=-0.37). CONCLUSION: 177Lu-PSMA-617 delivers high-absorbed
      doses to tumor with significant correlation between "whole body" tutor dose and
      PSA response. Patients receiving less than 10 Gy were unlikely to achieve a fall
      in PSA>=50%. Significant correlations between aspects of screening 68Ga-PET-CT
      and tumor and normal tissue dose were observed providing a rationale for patient
      specific dosing. Reduced salivary and kidney doses was observed in patients with
      a higher tumor burden. Parotid dose also reduced with increasing body mass and
      body surface area.

PMID- 30291193
TI  - Evidence of local concentration of alpha-particles from 211At-labeled antibodies
      in liver metastasis tissue.
AB  - We investigated the local concentration of alpha-particles from 211At-labeled
      trastuzumab antibodies against HER2 (human epidermal growth factor receptor
      type2) antigens in liver metastasis tissue of mice. Mice carrying metastatic
      cancer in their liver were injected with 211At-agent. After 12 hours, the liver
      was removed and sliced, and two tissue samples of liver tissues without lesions
      and one containing metastatic lesions were mounted on the CR-39 plastic nuclear
      track detector. Microscope images of the tissues on CR-39 were acquired. After
      irradiation for 31 hours, the tissues were removed from CR-39. A microscope image
      of alpha-particle tracks on CR-39 was acquired after chemical etching. The
      positions of each tissue sample and the emitted alpha-particle tracks were
      adjusted to the same coordinates. The positional distribution of alpha-particle
      tracks emitted from 211At was consistent within the tissue. The alpha-particle
      tracks were mainly allocated in the tumor region of the tissue. The absorbed dose
      in individual cells segmented by 10 um intervals was obtained by the
      spectroscopic analysis of the LET (linear energy transfer) spectrum. The
      concentration efficiency, the track density ratio of alpha-particle tracks in the
      necrotized tissue, which was the tumor region, to the normal tissue, was found to
      be 6.0 +/- 0.2. In the tumor region, the high LET alpha-particles deposited a
      large enough dose to cause lethal damage to the cancer cells. The total absorbed
      dose ranged from 1 to 7 Gy with a peak at around 2 Gy, which would correspond to
      2-3 times higher biologically equivalent dose because of the high RBE of the
      alpha-particles emitted from 211At.

PMID- 30291195
TI  - Design of Cerenkov-assisted Photoactivation of TiO2 Nanoparticles and Reactive
      Oxygen Species Generation for Cancer Treatment.
AB  - The use of Cerenkov radiation (CR) to activate nanoparticles in situ has recently
      been shown to control cancerous tumor growth. While the methodology has been
      demonstrated to work, to better understand the mechanistic steps, we develop a
      mathematical model that integrates Cerenkov physics, light interaction with
      matter, and photocatalytic reaction engineering. The model describes a detailed
      pathway for localized reactive oxygen species (ROS) generation from the Cerenkov
      assisted photocatalytic activity of TiO2 The model predictions are verified by
      comparing to the experimental reports in the literature. It is then used to
      investigate the effect of various parameters - size of TiO2 nanoparticles,
      concentration of TiO2 nanoparticles, and activity of the radionuclide [2-deoxy-2
      18F-fluoro-D-glucose (18F-FDG)] on the number of photons and ROS generation. The
      importance of nanoparticle size on ROS generation for cancerous tumor growth
      control is elucidated, and an optimal size is proposed. The model presented here
      can be used for other radionuclides and nanoparticles and can provide guidance to
      the concentration and size of TiO2 nanoparticles and activity of radionuclide
      needed for efficient cancer therapy.

PMID- 30291194
TI  - Efficacy and Safety of High-Specific-Activity I-131 MIBG Therapy in Patients with
      Advanced Pheochromocytoma or Paraganglioma.
AB  - Patients with metastatic or unresectable (advanced) pheochromocytoma or
      paraganglioma (PPGL) have poor prognoses and few treatment options. This
      multicenter, phase 2 trial evaluated the efficacy and safety of high-specific
      activity I-131 meta-iodobenzylguanidine (HSA I-131 MIBG) in patients with
      advanced PPGL. Methods: In this open-label, single-arm study, 81 PPGL patients
      were screened for enrollment, and 74 received a treatment-planning dose of HSA I
      131 MIBG. 68 patients with advanced PPGL received at least one therapeutic dose
      (~18.5 GBq) of HSA I-131 MIBG intravenously. The primary endpoint was the
      proportion of patients with at least a 50% reduction in baseline antihypertensive
      medication use lasting at least 6 months. Secondary endpoints included objective
      tumor response as assessed by Response Evaluation Criteria in Solid Tumors
      version 1.0; biochemical tumor marker response; overall survival (OS); and
      safety. Results: Of the 68 patients who received at least one therapeutic dose of
      HSA I-131 MIBG, 17 (25%; 95% CI, 16-37%) had a durable reduction in baseline
      antihypertensive medication use. Among 64 patients with evaluable disease, 59
      (92%) had a partial response or stable disease as the best objective response
      within 12 months. Decreases in elevated (>=1.5 times the upper limit of normal
      (ULN) at baseline) serum CgA levels were observed with confirmed complete and
      partial responses 12 months after treatment in 19 of 28 patients (68%). The
      median OS duration was 36.7 months (95% CI, 29.9-49.1 months). The most common
      treatment-emergent adverse events were nausea, myelosuppression, and fatigue. No
      patients had drug-related acute hypertensive events during or after the
      administration of HSA I-131 MIBG. Conclusion: HSA I-131 MIBG offers multiple
      benefits, including sustained blood pressure control and tumor response in PPGL
      patients.

PMID- 30291196
TI  - An imager's guide to perineural tumor spread in head and neck cancers:
      radiological footprints on 18F-FDG PET with CT and MRI correlates.
AB  - Perineural spread refers to tumor growth along large nerves, a macroscopic
      analogue of microscopic perineural invasion. This phenomenon most commonly occurs
      in head and neck, but its incidence varies with histologic tumor subtype.
      Perineural spread results from a complex molecular interplay between tumor cells,
      nerves, and connective stroma. Perineural spread is clinically underdiagnosed
      despite its impact on patients' prognosis and management. The role of 18F
      fluorodeoxyglucose positron emission tomography (18F-FDG PET) in assessment of
      perineural spread in head and neck cancer remains to be explored, in contrast to
      magnetic resonance imaging (MRI) as the established gold standard. In patients
      with perineural spread, 18F-FDG PET shows both abnormality along the course of
      the involved nerve and muscular changes secondary to denervation. Assessment of
      perineural spread on 18F-FDG PET requires knowledge of relevant neural pathways,
      and it can be improved by correlation with anatomic imaging, additional image
      processing, and review of clinical context.

PMID- 30291197
TI  - Nuclear Neuroimaging in Social Anxiety Disorder: A Review.
AB  - In psychiatric research, nuclear imaging complements MRI. A recent neuroimaging
      review of social anxiety disorder focused predominantly on MRI, omitting the
      contribution of nuclear imaging methods. Nuclear imaging investigations of neural
      activity are sparse but have generally yielded results consistent with studies
      performed using MRI. Evidence for disturbances in neurotransmitter systems in
      social anxiety disorder is limited but suggestive of both serotonergic and
      dopaminergic dysfunction. Research focusing on additional molecular targets using
      existing and novel tracers, combined with recent technologic innovations and
      trends in collaborative methodology, may shape future nuclear imaging endeavors
      in this field.

PMID- 30291198
TI  - Polycomb Group Transcriptional Repressor: Suppress to Sustain.

PMID- 30291199
TI  - Stress Management: OsIDS1 Modulates Histone Deacetylation to Repress Salt
      Tolerance Genes.

PMID- 30291200
TI  - Towards 'a balanced delegation' or enhancing global health governance? Analysis
      of parties' participation in the Conference of the Parties to WHO Framework
      Convention on Tobacco Control.
AB  - INTRODUCTION: The success of the WHO Framework Convention on Tobacco Control
      (FCTC) depends on parties' active participation in its governance and
      implementation, particularly via biennial Conference of the Parties (COP)
      meetings. The COP's efficacy is threatened by declining attendance and reductions
      in travel support for low-income and middle-income countries, and there are
      growing concerns about transparency and representation in country delegations
      amid industry efforts to shape their composition. METHODS: We examined parties'
      participation in the COP based on official meeting records, and the relationship
      between attendance and strength of tobacco control based on national global
      tobacco control reports. RESULTS: Attendance at the COP has decreased over time,
      and at several meetings would have fallen below 66% (the threshold for decision
      making) if it was not for high levels of participation among low-income and lower
      middle-income countries. Despite their higher attendance at COP meetings, these
      countries represent a smaller share of meeting attendees due to the smaller size
      of their delegations. Additionally, there has been a decline in the proportion of
      delegates from ministries of health and tobacco control focal points. Nationally,
      COP participation is correlated with stronger tobacco control policies;
      attendance by low-income countries has a strong correlation with implementation
      of advertising bans, while attendance among high-income and lower-middle-income
      countries shows a moderate correlation with implementation of tobacco taxes.
      CONCLUSIONS: Supporting states to actively engage in the COP is crucial for
      ongoing FCTC implementation, strengthening national capacity for tobacco control,
      and protecting the legitimacy and efficacy of global health governance.

PMID- 30291201
TI  - Heated tobacco product regulation under US law and the FCTC.
AB  - Tobacco companies are marketing new 'heated tobacco products' (HTPs) composed of
      battery-powered holders, chargers and tobacco plugs or sticks. The non-tobacco
      HTP components have escaped effective regulation under many countries' tobacco
      control laws because they are packaged and sold separately from the tobacco
      containing components. In the USA, HTPs cannot be marketed unless the Food and
      Drug Administration determines that allowing their sale would be 'appropriate for
      the protection of the public health'. Philip Morris International (PMI) is
      seeking permission to market its IQOS HTP in the USA with 'modified risk tobacco
      product' (MRTP) claims that it reduces exposure to harmful substances and is less
      harmful than other tobacco products. However, PMI has not submitted adequate
      scientific evidence required by US law to demonstrate that the product is
      significantly less harmful to users than other tobacco products, that its
      labelling would not mislead consumers, or that its marketing-with or without MRTP
      claims-would benefit the health of the population as a whole. Parties to the WHO
      Framework Convention on Tobacco Control (FCTC) must take measures to reduce
      tobacco use and nicotine addiction, and prevent false or misleading tobacco
      product labelling, advertising and promotions; the introduction of new HTPs must
      be assessed according to these goals. All components of HTPs should be regulated
      at least as stringently as existing tobacco products, including restrictions on
      labelling, advertising, promotion and sponsorship, sales to minors, price and
      taxation policies and smokefree measures. There is nothing in US law or the FCTC
      that prevents authorities from prohibiting HTPs.

PMID- 30291202
TI  - Tobacco taxation, illegal cigarette supply and geography.
AB  - BACKGROUND: In Uruguay, real tobacco taxes increased significantly during 2005
      2010 and 2014-2017 and decreased during 2010-2014. The effects of these tax
      changes on illegal and legal cigarette usage differed significantly when we
      compared cities in the middle and south of the country with cities on the border.
      OBJECTIVE: This paper analyses whether supply side factors such as geographical
      location, distribution networks and the effectiveness of tobacco control play a
      significant role in sales and use of illegal cigarettes when tobacco taxes
      change, particularly given the price gap between legal and lower-priced illegal
      cigarettes. METHODS: Using the International Tobacco Control Evaluation Project
      Uruguay Survey data (2008, 2010, 2012 and 2014), choices among illegal, legal and
      roll-your-own cigarettes are estimated as a function of smokers' geographical
      location, an indicator of illegal cigarette supply, and controlling for
      socioeconomic and demographic variables. Smoking behaviours in Montevideo,
      Durazno and Maldonado were compared with those in two border cities, Salto and
      Rivera, where illegal cigarette prevalence may differ. FINDINGS: An increase in
      taxes on manufactured legal and roll-your-own cigarettes increased the odds that
      smokers in cities near the borders and women switched down to illegal cigarettes.
      City geographical location, controls effectiveness and distribution networks may
      play a significant role in accessibility of illegal cigarettes. To improve the
      effectiveness of increased taxes and prices in reducing smoking, policy-makers
      may consider specific policies intended to reduce access to illegal cigarettes,
      such as ratification and effective implementation of the Protocol to Eliminate
      Illicit Trade in Tobacco Products of WHO.

PMID- 30291203
TI  - In Vivo Expansion of Regulatory T Cells with IL-2/IL-2 Antibody Complex Protects
      against Transient Ischemic Stroke.
AB  - Regulatory T cells (Tregs) are known to protect against ischemic stroke. However,
      the low frequency of Tregs restricts their clinical utility. This study
      investigated whether expanding the number of Tregs in vivo with the IL-2/IL-2
      antibody complex (IL-2/IL-2Ab) could improve stroke outcomes and further
      elaborated the mechanisms of protection in male mice. C57BL/6 mice received IL
      2/IL-2Ab or isotype IgG (IsoAb) intraperitoneally for 3 d before (pretreatment)
      or starting 2 h after (posttreatment) 60 min middle cerebral artery occlusion
      (MCAO). IL-2/IL-2Ab selectively increased the number of Tregs in the blood,
      spleen, and lymph nodes. The IL-2/IL-2Ab treatment significantly reduced infarct
      volume, inhibited neuroinflammation, and improved sensorimotor functions, as
      manifested by rotarod test and foot fault test, compared with IsoAb-treated
      stroke mice. Treg depletion was then achieved by diphtheria toxin (DT) injection
      into transgenic mice expressing the DT receptor under the control of the Foxp3
      promoter (DTR mice). The depletion of Tregs completely eliminated IL-2/IL-2Ab
      afforded neuroprotection. Interestingly, adoptive transfer of Tregs collected
      from IL-2/IL-2Ab-treated mice demonstrated more potent neuroprotection than an
      equal number of Tregs prepared from IsoAb-treated mice, suggesting that IL-2/IL
      2Ab not only elevated Treg numbers, but also boosted their functions.
      Mechanistically, IL-2/IL-2Ab promoted the expression of CD39 and CD73 in expanded
      Tregs. CD73 deficiency diminished the protective effect of IL-2/IL-2Ab-stimulated
      Tregs in stroke mice. The results show that IL-2/IL-2Ab expands Tregs in vivo and
      boosts their immunomodulatory function. The activation of CD39/CD73 signaling in
      Tregs may participate as a potential mechanism underlying IL-2/IL-2Ab-afforded
      neuroprotection against ischemic brain injury.SIGNIFICANCE STATEMENT Regulatory T
      cells (Tregs) are known to protect against ischemic stroke. However, the low
      frequency of Tregs restricts their clinical utility. This study reported that
      systemic administration of the IL-2/IL-2 antibody complex (IL-2/IL-2Ab) robustly
      and selectively expanded the number of Tregs after stroke. IL-2/IL-2Ab
      pretreatment or posttreatment significantly improved stroke outcomes in a rodent
      model of ischemic stroke. We further discovered that IL-2/IL-2Ab not only
      elevated Treg numbers, but also boosted their functions and enhanced the
      expression of CD39 and CD73. Using CD73-deficient mice, we confirmed the
      importance of CD73 in the protective effect of IL-2/IL-2Ab-stimulated Tregs in
      stroke mice. These results shed light on IL-2/IL-2Ab as a clinically feasible
      immune therapy to boost endogenous Treg responses and ameliorate ischemic brain
      injury.

PMID- 30291204
TI  - Instantaneous Midbrain Control of Saccade Velocity.
AB  - The ability to interact with our environment requires the brain to transform
      spatially represented sensory signals into temporally encoded motor commands for
      appropriate control of the relevant effectors. For visually guided eye movements,
      or saccades, the superior colliculus (SC) is assumed to be the final stage of
      spatial representation, and instantaneous control of the movement is achieved
      through a rate code representation in the lower brain stem. We investigated
      whether SC activity in nonhuman primates (Macaca mulatta, 2 male and 1 female)
      also uses a dynamic rate code, in addition to the spatial representation. Noting
      that the kinematics of amplitude-matched movements exhibit trial-to-trial
      variability, we regressed instantaneous SC activity with instantaneous eye
      velocity and found a robust correlation throughout saccade duration. Peak
      correlation was tightly linked to time of peak velocity, the optimal efferent
      delay between SC activity and eye velocity was constant at ~12 ms both at onset
      and during the saccade, and SC neurons with higher firing rates exhibited
      stronger correlations. Moreover, the strong correlative relationship and constant
      efferent delay observation were preserved when eye movement profiles were
      substantially altered by a blink-induced perturbation. These results indicate
      that the rate code of individual SC neurons can control instantaneous eye
      velocity and argue against a serial process of spatial-to-temporal
      transformation. They also motivated us to consider a new framework of saccade
      control that does not incorporate traditionally accepted elements, such as the
      comparator and resettable integrator, whose neural correlates have remained
      elusive.SIGNIFICANCE STATEMENT All movements exhibit time-varying features that
      are under instantaneous control of the innervating neural command. At what stage
      in the brain is dynamical control present? It is well known that, in the
      skeletomotor system, neurons in the motor cortex use dynamical control. In the
      oculomotor system, in contrast, instantaneous velocity control of saccadic eye
      movements is not thought to be enforced until the lower brainstem. Using
      correlations between residual signals across trials, we show that instantaneous
      control of saccade velocity is present earlier in the visuo-oculomotor neuraxis,
      at the level of superior colliculus. The results require us to consider alternate
      frameworks of the neural control of saccades.

PMID- 30291206
TI  - Balloon remodeling-assisted Woven EndoBridge technique: description and
      feasibility for complex bifurcation aneurysms.
AB  - BACKGROUND: Woven EndoBridge (WEB) deployment remains challenging in aneurysms
      with a complex shape or orientation. OBJECTIVE: To show that embolization of wide
      neck bifurcation aneurysms using the WEB device balloon remodeling-assisted
      technique is a feasible and elegant endovascular solution compared with other
      techniques, such as balloon remodeling or stent-assisted coiling. MATERIALS AND
      METHODS: 10 cases (10 aneurysms in 9 patients) of balloon remodeling-assisted WEB
      treatment of unruptured complex bifurcation aneurysms were treated in our
      institution and retrospectively analyzed. Details of clinical presentations,
      technical details, perioperative and postoperative complications, and outcomes
      were collected. Immediate and long-term angiographic results were also evaluated.
      RESULTS: Aneurysms included six middle cerebral artery aneurysms, one anterior
      communicating artery aneurysm, one posterior communicating artery aneurysm, one
      basilar artery aneurysm, and one T-shaped carotid aneurysm. Mean dome width was
      6.55 mm, mean neck size 4.5 mm, mean height 4.79 mm, and mean dome-to-neck ratio
      was 1:1.46. Treatment was performed exclusively with the balloon remodeling
      assisted WEB technique in all cases. The device was successfully deployed in
      every case. Periprocedural thromboembolic or hemorrhagic events did not occur.
      The modified Rankin Scale score at discharge was 0 for all patients. At mid-term
      or long-term angiographic follow-up, adequate occlusion was observed in 7
      aneurysms from 8 controlled cases (87.5%), and one patient (2 aneurysms) did not
      have angiographic follow-up. CONCLUSION: The balloon remodeling-assisted WEB
      technique seems to be a safe and effective solution for endovascular treatment of
      unruptured wide-neck bifurcation aneurysms with specific complex anatomy.
      However, further studies are needed to evaluate the rate of complications and
      long-term efficacy.

PMID- 30291205
TI  - Temporal Contingencies Determine Whether Adaptation Strengthens or Weakens
      Normalization.
AB  - A fundamental and nearly ubiquitous feature of sensory encoding is that neuronal
      responses are strongly influenced by recent experience, or adaptation.
      Theoretical and computational studies have proposed that many adaptation effects
      may result in part from changes in the strength of normalization signals.
      Normalization is a "canonical" computation in which a neuron's response is
      modulated (normalized) by the pooled activity of other neurons. Here, we test
      whether adaptation can alter the strength of cross-orientation suppression, or
      masking, a paradigmatic form of normalization evident in primary visual cortex
      (V1). We made extracellular recordings of V1 neurons in anesthetized male
      macaques and measured responses to plaid stimuli composed of two overlapping,
      orthogonal gratings before and after prolonged exposure to two distinct adapters.
      The first adapter was a plaid consisting of orthogonal gratings and led to
      stronger masking. The second adapter presented the same orthogonal gratings in an
      interleaved manner and led to weaker masking. The strength of adaptation's
      effects on masking depended on the orientation of the test stimuli relative to
      the orientation of the adapters, but was independent of neuronal orientation
      preference. Changes in masking could not be explained by altered neuronal
      responsivity. Our results suggest that normalization signals can be strengthened
      or weakened by adaptation depending on the temporal contingencies of the adapting
      stimuli. Our findings reveal an interplay between two widespread computations in
      cortical circuits, adaptation and normalization, that enables flexible
      adjustments to the structure of the environment, including the temporal
      relationships among sensory stimuli.SIGNIFICANCE STATEMENT Two fundamental
      features of sensory responses are that they are influenced by adaptation and that
      they are modulated by the activity of other nearby neurons via normalization. Our
      findings reveal a strong interaction between these two aspects of cortical
      computation. Specifically, we show that cross-orientation masking, a form of
      normalization, can be strengthened or weakened by adaptation depending on the
      temporal contingencies between sensory inputs. Our findings support theoretical
      proposals that some adaptation effects may involve altered normalization and
      offer a network-based explanation for how cortex adjusts to current sensory
      demands.

PMID- 30291207
TI  - Predictors and impact of hemorrhagic transformations after endovascular
      thrombectomy in patients with acute large vessel occlusions.
AB  - BACKGROUND: Predictors and impact of hemorrhagic transformation (HT) after
      thrombectomy remain to be elucidated. OBJECTIVE: To investigate the independent
      predictors and impact of each hemorrhagic infarction (HI) and parenchymal
      hematoma (PH) after thrombectomy in patients with acute stroke due to
      intracranial large vessel occlusion (LVO). MATERIALS AND METHODS: We
      retrospectively reviewed data from 400 patients with acute LVO who underwent
      thrombectomy. Logistic regression analyses were performed to determine
      independent predictors of HI and PH on post-treatment CT scans. Associations
      between HT and poor outcome (modified Rankin Scalescore >=3) at 90 days were
      analyzed. RESULTS: HT was observed in 98 patients (62 HIs (15.5%) and 36 PHs
      (9%)). Independent predictors of HI were male sex, atrial fibrillation, and time
      from symptom onset to groin puncture. Hyperlipidemia (OR=0.221, 95% CI 0.064 to
      0.767, P=0.017) and successful reperfusion (OR=0.246, 95% CI 0.093 to 0.651,
      P=0.005) were independently associated with a lower chance of PH, while
      hypertension (OR=2.260, 95% CI 1.014 to 5.035, P=0.046) and longer procedure
      duration (OR=1.046, 95% CI 1.016 to 1.077, P=0.003) were independently associated
      with a higher chance of PH. Only PH (OR=10.154, 95% CI 3.260 to 31.632, P<0.001)
      was an independent predictor of poor outcome. CONCLUSIONS: PH is independently
      associated with poor outcome, whereas HI does not predict outcome after
      thrombectomy in patients with acute LVO. Our findings suggest that rapid and
      successful reperfusion is essential to prevent PH in patients undergoing
      thrombectomy for acute LVO. In addition, our study suggests that hyperlipidemia
      is associated with a lower risk of PH in such patients.

PMID- 30291208
TI  - Selective compromise of hypoplastic posterior communicating artery variants with
      aneurysms treatable by coil embolization: clinical and radiologic outcomes.
AB  - BACKGROUND: Posterior communicating artery (PcoA) compromise may serve as
      adjunctive treatment in patients with hypoplastic variants of PcoA who undergo
      coil embolization of PcoA aneurysms. However, procedural safety and the
      propensity for later recanalization are still unclear. OBJECTIVE: To evaluate
      clinical and radiologic outcomes of coil embolization in this setting, focusing
      on compromise of PcoA. METHODS: As a retrospective review, we examined 250
      patients harboring 291 aneurysms of hypoplastic PcoAs, all consecutively treated
      by coil embolization between January 2004 and June 2016. PcoA compromise was
      undertaken in conjunction with 81 of the treated aneurysms (27.8%; incomplete 53;
      complete 28). Medical records and radiologic data were assessed during extended
      monitoring. RESULTS: During the mean follow-up of 33.9+/-24.6 months (median 36
      months), a total of 107 (36.8%) coiled aneurysms showed recanalization (minor 50;
      major 57). Recanalization rates were as follows: PcoA preservation 40.5%
      (85/210); incomplete PcoA occlusion 34.0% (18/53); complete PcoA occlusion 14.3%
      (4/28). Aneurysms >7 mm (HR 3.40; P<0.01), retreatment for recanalization (HR
      3.23; P<0.01), and compromise of PcoA (P<0.01) emerged from multivariate analysis
      as significant risk factors for recanalization. Compared with PcoA preservation,
      complete PcoA compromise conferred more favorable outcomes (HR 0.160), whereas
      incomplete compromise of PcoA fell short of statistical significance.
      Thromboembolic infarction related to PcoA compromise did not occur in any
      patient. CONCLUSION: PcoA compromise in conjunction with coil embolization of
      PcoA aneurysms appears safe in hypoplastic variants of PcoA, helping to prevent
      recanalization if complete occlusion is achieved.

PMID- 30291209
TI  - Direct endovascular thrombectomy and bridging strategies for acute ischemic
      stroke: a network meta-analysis.
AB  - OBJECTIVES: The present Bayesian network meta-analysis aimed to compare the
      various strategies for acute ischemic stroke: direct endovascular thrombectomy
      within the thrombolysis window in patients with no contraindications to
      thrombolysis (DEVT); (2) direct endovascular thrombectomy secondary to
      contraindications to thrombolysis (DEVTc); (3) endovascular thrombectomy in
      addition to thrombolysis (IVEVT); and (4) thrombolysis without thrombectomy
      (IVT). METHODS: Six electronic databases were searched from their dates of
      inception to May 2017 to identify randomized controlled trials (RCTs) comparing
      IVT versus IVEVT, and prospective registry studies comparing IVEVT versus DEVT or
      IVEVT versus DEVTc. Network meta-analyses were performed using ORs and 95% CIs as
      the summary statistic. RESULTS: We identified 12 studies (5 RCTs, 7 prospective
      cohort) with a total of 3161 patients for analysis. There was no significant
      difference in good functional outcome at 90 days (modified Rankin Scale score
      <=2) between DEVT and IVEVT. There was no significant difference in mortality
      between all treatment groups. DEVT was associated with a 49% reduction in
      intracranial hemorrhage (ICH) compared with IVEVT (OR 0.51; 95% CI 0.33 to 0.79),
      due to reduction in rates of asymptomatic ICH (OR 0.47; 95% CI 0.29 to 0.76).
      Patients treated with DEVT had higher rates of reperfusion compared with IVEVT
      (OR 1.73; 95% CI 1.04 to 2.94). CONCLUSIONS: To our knowledge, this is the first
      network meta-analysis to be performed in the era of contemporary mechanical
      thrombectomy comparing DEVT and DEVTc. Our analysis suggests the addition of
      thrombolysis prior to thrombectomy for large vessel occlusions may not be
      associated with improved outcomes.

PMID- 30291210
TI  - Novel role for cardiac myocyte-derived beta-2 microglobulin in mediating cardiac
      fibrosis.
AB  - Hypertension is a significant risk factor for the development of cardiovascular
      ailments, including ischemic heart disease and diastolic dysfunction. In a recent
      issue of Clinical Science, Li et al. [Clin. Sci. (2018) 132, 1855-1874] report
      that beta-2 microglobulin (beta2M) is a novel secreted soluble factor released by
      cardiac myocytes during pressure overload that promotes profibrotic gene
      expression in cardiac fibroblasts both in vitro and in vivo Their study further
      identifies elevated beta2M levels as a possible biomarker for hypertensive
      patients with cardiac complications. The authors propose a mechanism that
      mechanically stretched cardiomyocytes release soluble beta2M which, through
      paracrine communication with cardiac fibroblasts, transactivates epidermal growth
      factor receptor (EGFR) to initiate acute signal transduction and up-regulate
      profibrotic genes, thereby promoting fibrosis. Here, we will discuss the
      background, significance of the study, alternative mechanisms, and future
      directions.

PMID- 30291211
TI  - Protective effects of Fragaria ananassa methanolic extract in a rat model of
      cadmium chloride-induced neurotoxicity.
AB  - Cadmium (Cd) is a common environmental toxicant that has harmful effects on
      plants, animals, and humans. The present study evaluated the protective effects
      of Fragaria ananassa methanolic extract (SME) on cadmium chloride (CdCl2)-induced
      neuronal toxicity in rats. Male albino rats were intraperitoneally (i.p) injected
      with CdCl2 (6.5 mg/kg) for 5 days with or without the SME (250 mg/kg). We
      measured the levels of Cd, lipid peroxidation (LPO), nitric oxide, glutathione
      (GSH), and oxidative enzymes such as superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase, and glutathione reductase (GR) in the whole brain
      homogenate. Compared with the control group, the Cd-intoxicated group showed a
      marked increase in the brain levels of Cd, LPO, and nitric oxide and a decrease
      in the levels of GSH and all tested antioxidant enzymes. Compared with Cd
      intoxicated rats, the rats pretreated with SME showed restoration of oxidative
      balance in the brain tissue. While the expression of brain SOD2, CAT, glutathione
      peroxidase 1, and GR was down-regulated in the Cd-treated group, the expression
      of these enzymes was up-regulated in rats pretreated with SME. In addition,
      administration of SME before CdCl2 increased the Bcl-2 expression, but
      significantly decreased the expression of Bax. Immunohistochemical analysis
      showed that compared with Cd-intoxicated rats, rats pretreated with SME showed a
      decrease in the protein expression of tumor necrosis factor alpha (TNF-alpha).
      Our findings indicate that SME protects the brain tissue from Cd-induced neuronal
      toxicity by improving the antioxidant system and increasing antiapoptotic and
      anti-inflammatory activities.

PMID- 30291212
TI  - MiR-140-5p suppresses retinoblastoma cell growth via inhibiting c-Met/AKT/mTOR
      pathway.
AB  - MiR-140-5p is low expression and acts as a tumor suppressor in various types of
      human cancers. However, the potential role of miR-140-5p in retinoblastoma (RB)
      remains unknown. In the present study, we performed the miRNA microarray analysis
      to investigate whether miRNAs expression are associated with RB tumorigenesis in
      RB tissues. We found that a large set of miRNAs were ectopic expressions and miR
      140-5p is most significantly down-regulated in human RB tissues compared with
      normal retinas. In addition, low miR-140-5p expression is associated with
      clinicopathological features (differentiation, invasion, T classification, N
      classification, cTNM stage, and largest tumor base) and poor survival in RB
      patients. Furthermore, our results showed that overexpression of miR-140-5p
      suppresses proliferation and induces apoptosis and cell cycle arrest in RB cell.
      Meanwhile, we confirmed that c-Met is the functional target of miR-140-5p in RB
      cell, and miR-140-5p expression is negatively correlated with c-Met in RB
      tissues. We also found that inhibition of c-Met also suppresses proliferation and
      induces apoptosis and cell cycle arrest in RB cell. Interestingly, c-Met can
      rescue the suppressive effects of miR-140-5p on RB cell growth and cell cycle
      arrest. More importantly, our findings indicated that miR-140-5p may inhibit cell
      growth via blocking c-Met/AKT/mTOR signaling pathway. Collectively, these results
      suggested that miR-140-5p might be a potential biomarker and target in the
      diagnosis and treatment of RB.

PMID- 30291213
TI  - The association of POLR2E rs3787016 polymorphism and cancer risk: a Chinese case
      control study and meta-analysis.
AB  - How single nucleotide polymorphisms in long non-coding RNAs are involved in
      cancer susceptibility remains poorly understood. We hypothesized that polymerase
      II polypeptide E (POLR2E) rs3787016 polymorphism, identified in a genome-wide
      association study of prostate cancer, might be a common genetic risk factor for
      cancer risk. To address this issue, we here conducted a case-control study to
      investigate the association of POLR2E rs3787016 polymorphism with risk of liver
      and lung cancer (including 800 normal controls, 480 liver cancer patients, and
      550 lung cancer patients), followed by a meta-analysis. The genotyping was
      performed by polymerase chain reaction-restriction fragment length polymorphism
      and confirmed by sequencing. Although no significant association was found for
      rs3787016 with risk of liver or lung cancer, the further stratified analysis
      identified that rs3787016 contributed to liver cancer risk particularly for over
      than 60 years individuals who drink. Moreover, the meta-analysis demonstrated
      that rs3787016 was associated with overall cancer risk and prostate cancer risk.
      Collectively, the POLR2E rs3787016 polymorphism may be a valuable biomarker for
      cancer predisposition.

PMID- 30291214
TI  - Placenta-specific 9, a putative secretory protein, induces G2/M arrest and
      inhibits the proliferation of human embryonic hepatic cells.
AB  - Background: Placenta-specific 9 (Plac9) is a putative secreted protein that was
      first discovered in the context of embryogenesis. The expression pattern of Plac9
      during embryogenesis, together with the results of recent reports, suggest that
      Plac9 may play a role in the liver development. The present study was conducted
      to investigate the secretory characteristics of Plac9 and its potential role in
      liver cell physiology. Methods: Immunofluorescence was employed to identify the
      subcellular distribution of Plac9 Cellular proliferative activity was analyzed by
      MTT assay and cell colony formation. The cell cycle distribution of Plac9 was
      analyzed by flow cytometry, and a functional analysis was performed using L02
      cells following their stable infection with a lentivirus over-expressing Plac9
      Results: Plac9 is a novel protein that is localized to the cytoplasm and may be
      secreted through the classic endoplasmic reticulum-Golgi route. The
      overexpression of Plac9 inhibits cell growth and induces G2/M phase arrest.
      Conclusion: Our findings reveal a novel role for Plac9 in regulating cell growth.

PMID- 30291215
TI  - The Chinese medicine Chai Hu Li Zhong Tang protects against non-alcoholic fatty
      liver disease by activating AMPKalpha.
AB  - An effective treatment for non-alcoholic fatty liver disease (NAFLD) is urgently
      needed. In the present study, we investigated whether the Chinese medicine Chai
      Hu Li Zhong Tang (CHLZT) could protect against the development of NAFLD. Rats in
      an animal model of NAFLD were treated with CHLZT, and their serum levels of
      cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL
      C), low density lipoprotein-cholesterol (LDL-C), aspartate aminotransferase
      (AST), and alanine aminotransferase (ALT) were detected with an automatic
      biochemical analyzer. A cellular model of NAFLD was also established by culturing
      HepG2 cells in a medium that contained a long chain fat emulsion. Those cells
      were treated with CHLZT that contained serum from rats. After treatment, the
      levels of adenylate-activated protein kinase (AMPK) alpha (AMPKalpha), p
      AMPKalpha, acetyl coenzyme A carboxylase (ACC) alpha (ACCalpha), pACCalpha,
      PPARgamma, and SREBP-2 were detected. The AMPK agonist, acadesine (AICAR), was
      used as a positive control compound. Our results showed that CHLZT or AICAR
      significantly decreased the serum levels of TG, TC, LDL-C, AST, ALT, and insulin
      in NAFLD rats, and significantly increased their serum HDL-C levels. Treatments
      with CHLZT or AICAR significantly decreased the numbers of lipid droplets in
      NAFLD liver tissues and HepG2 cells. CHLZT and AICAR increased the levels of p
      AMPKalpha and PPARgamma in the NAFLD liver tissues and HepG2 cells, but decreased
      the levels of ACC-alpha, p-ACC-alpha, SREBP-2, and 3-hydroxyl-3-methylglutaryl
      coenzyme A reductase (HMGR). CHLZT protects against NAFLD by activating
      AMPKalpha, and also by inhibiting ACC activity, down-regulating SREBP2 and HMGR,
      and up-regulating PPAR-gamma. Our results suggest that CHLZT might be useful for
      treating NAFLD in the clinic.

PMID- 30291216
TI  - Inhibition of N-glycosylation by tunicamycin attenuates cell-cell adhesion via
      impaired desmosome formation in normal human epidermal keratinocytes.
AB  - N-Glycosylation affects protein functions such as location, stability, and
      susceptibility to proteases. Desmosomes in keratinocytes are essential to
      maintain epidermal tissue integrity to protect against environmental insults.
      However, it is not yet known whether N-glycosylation affects desmosomal functions
      in primary keratinocytes. Tunicamycin is an inhibitor of N-glycosylation that has
      been a useful tool in glycobiology. Therefore, we investigated the effect of
      inhibiting N-glycosylation by tunicamycin treatment on desmosomes in primary
      keratinocytes. In our experiments, cell-cell adhesive strength was reduced in
      tunicamycin-treated primary keratinocytes. TEM showed that desmosome formation
      was impaired by tunicamycin. Desmogleins (Dsgs) 1 and 3, which constitute the
      core structure of desmosomes, were well transported to the cell-cell borders, but
      the amount decreased and showed an aberrant distribution at the cell borders in
      tunicamycin-treated keratinocytes. The stability of both desmoglein proteins was
      also reduced, and they were degraded through both proteasomal and lysosomal
      pathways, although inhibiting degradation did not restore the cell-cell adhesion.
      Finally, tunicamycin induced desmosomal instability, enhancing their disassembly.
      In conclusion, these results indicate that N-glycosylation is critical to the
      desmosome complex to maintain cell-cell adhesive strength in primary
      keratinocytes.

PMID- 30291217
TI  - Biomarkers as predictive tools to test the in vivo anti-sarcoptic mange activity
      of propolis in naturally infested rabbits.
AB  - This study was designed to investigate the use of specific biomarkers, such as
      albumin, serum total protein, aspartate amino transferase (AST), globulin,
      alanine amino transferase (ALT), serum cortisol and alkaline phosphatase (ALP),
      as predictive tools for sarcoptic mange in rabbits. A total of 30 infested
      rabbits were equally divided into three treatment groups. Each group was
      administered either propolis, ivermectin, or propolis with ivermectin. Treated
      rabbit results were then compared to those of 10 infested untreated rabbits and
      10 healthy rabbits. The impact of treatment was assessed via microscopic
      examination of skin scrapings, clinical signs, and blood measurements relating to
      the liver. This study demonstrated that topical application of 10 % propolis
      ointment resulted in complete recovery from clinical signs and complete absence
      of mites based on microscopic examination after 10-15 days of treatment.
      Moreover, AST, ALP, ALT, and cortisol were determined to be acceptable biomarkers
      to track the response of diseased rabbits to the therapeutic use of propolis.

PMID- 30291218
TI  - Acidic pH promotes nucleus pulposus cell senescence through activating the p38
      MAPK pathway.
AB  - BACKGROUND: Nucleus pulposus (NP) cell senescence is an important cellular
      feature within the degenerative disc. It is known that a very acidic niche exists
      in the degenerative disc, which participates in regulating disc cell viability
      and matrix metabolism. OBJECTIVE: The present study was aimed to investigate the
      role and potential signaling transduction pathway of an acidic pH in regulating
      NP cell senescence. METHODS: Rat NP cells were cultured in an acidic pH of 7.2
      close to that in a healthy disc (Control group) or in an acidic pH of 6.2 close
      to that in a severe degenerative disc (Experiment group) for 10 days.
      Additionally, the experimental NP cells were incubated along with the inhibitor
      SB203580 to analyze the role of p38 MAPK pathway in this process. RESULTS:
      Compared with the control NP cells, experimental NP cells showed a suppressed
      cell proliferation potency, an increased G0/G1 phase fraction whereas a decreased
      S-phase fraction and a declined telomerase activity, an up-regulated expression
      of senescence-related molecules (p16 and p53), and a down-regulated expression of
      matrix-related moleucles (aggrecan and collagen II). Further analysis showed that
      inhibition of the p38 MAPK pathway partly reversed effects of acidic pH of 6.2 on
      the experimental NP cells. CONCLUSION: The very acidic niche identified in a
      severe degenerative disc promotes NP cell senescence through regulating the p38
      MAPK pathway. The present study provides a new mechanism that drives NP cell
      senescence during disc degeneration.

PMID- 30291219
TI  - Efficacy of novel immunotherapy regimens in patients with metastatic melanoma
      with germline CDKN2A mutations.
AB  - BACKGROUND: Inherited CDKN2A mutation is a strong risk factor for cutaneous
      melanoma. Moreover, carriers have been found to have poor melanoma-specific
      survival. In this study, responses to novel immunotherapy agents in CDKN2A
      mutation carriers with metastatic melanoma were evaluated. METHODS: CDKN2A
      mutation carriers that have developed metastatic melanoma and undergone
      immunotherapy treatments were identified among carriers enrolled in follow-up
      studies for familial melanoma. The carriers' responses were compared with
      responses reported in phase III clinical trials for CTLA-4 and PD-1 inhibitors.
      From publicly available data sets, melanomas with somatic CDKN2A mutation were
      analysed for association with tumour mutational load. RESULTS: Eleven of 19
      carriers (58%) responded to the therapy, a significantly higher frequency than
      observed in clinical trials (p=0.03, binomial test against an expected rate of
      37%). Further, 6 of the 19 carriers (32%) had complete response, a significantly
      higher frequency than observed in clinical trials (p=0.01, binomial test against
      an expected rate of 7%). In 118 melanomas with somatic CDKN2A mutations,
      significantly higher total numbers of mutations were observed compared with 761
      melanomas without CDKN2A mutation (Wilcoxon test, p<0.001). CONCLUSION: Patients
      with CDKN2A mutated melanoma may have improved immunotherapy responses due to
      increased tumour mutational load, resulting in more neoantigens and stronger
      antitumorous immune responses.

PMID- 30291220
TI  - AXL Is a Putative Tumor Suppressor and Dormancy Regulator in Prostate Cancer.
AB  - Prostate cancer bone metastasis remains lethal and incurable, and often arises
      years after elimination of the primary tumor. It is unclear what underlies the
      decades-long clinical latency before recurrence, but evidence points to the
      existence of dormant residual tumor cells that disseminated before the primary
      tumor was eliminated. To design therapies to prevent progression of disseminated
      tumor cells (DTC) into lethal metastases, it is crucial to understand the
      mechanism(s) underlying this dormancy. The current study functionally validated
      our previous observation that implicated the GAS6/AXL axis in mediating DTC
      dormancy in the bone marrow. AXL-null and AXL-overexpressing prostate cancer cell
      lines were generated to determine if AXL was necessary and/or sufficient for
      dormancy. Characterization of these cells in vitro and using in vivo mouse models
      of DTC growth demonstrated that AXL was indeed sufficient to induce dormancy, but
      was unable to maintain it long-term and was not absolutely required for a
      dormancy period. Clinically, AXL expression correlated with longer survival in
      prostate cancer patients, and AXL was not expressed by cancer cells in primary or
      metastatic tissue. These data point to a tumor-suppressive role for AXL in
      prostate cancer, and future work is required to determine if AXL is expressed on
      human bone marrow DTCs.Implications: The ability of AXL to initiate but not
      maintain dormancy, coupled with its dispensability, suggests that targeting AXL
      alone will not prevent lethal metastatic outgrowth, and likely a cooperative
      network of factors exists to mediate long-term cellular dormancy. Mol Cancer Res;
      1-14. (c)2018 AACR.

PMID- 30291221
TI  - Knockdown of Ubiquitin Associated Protein 2-Like (UBAP2L) Inhibits Growth and
      Metastasis of Hepatocellular Carcinoma.
AB  - BACKGROUND The aim of this study was to explore the influence of ubiquitin
      associated protein 2-like (UBAP2L) on the growth and metastasis of hepatocellular
      carcinoma (HCC) and its potential underlying mechanism. MATERIAL AND METHODS
      UBAP2L gene was knocked down in SMMC-7721 by RNA interference and cell function
      experiments were performed. A subcutaneous xenograft tumor model was constructed
      to examine the effect of UBAP2L silence on HCC growth. Finally, the whole genomic
      microarrays were used to screen the potential mechanism of UBAP2L in regulating
      the biological function of HCC. RESULTS Compared with those in the control group,
      the cell proliferation and clone formation were significantly reduced, cell cycle
      was arrested in G2/M phase, the number of apoptotic cells was remarkably
      increased, and the abilities of vascular formation and cell migration and
      metastasis were dramatically weakened in the shUBAP2L group (All P<0.05). UBAP2L
      knockdown significantly suppressed the tumor growth of HCC in vivo. Moreover, a
      total of 320 genes changed significantly after UBAP2L knockdown, among which, 159
      genes were upregulated and 161 genes were downregulated. Then, gene enrichment
      analysis revealed that PI3K/AKT and P53 signal pathway were the most significant
      in the top 10 enrichments. Finally, Western blot analysis verified that UBAP2L
      knockdown caused the increase of P21 and PTEN and decrease of CDK1, CCNB1, p
      PI3K, and p-AKT. CONCLUSIONS UBAP2L plays an oncogenic role in HCC, and knockdown
      of its expression significantly inhibits HCC growth and metastasis, which may be
      related to the regulation of PI3K/AKT and P53 signaling pathways by UBAP2L.

PMID- 30291222
TI  - A Case Report of Recurrent Metastatic Sebaceous Carcinoma Which Showed Favorable
      Response Tt Non-Fluorouracil Based Chemotherapy.
AB  - BACKGROUND Sebaceous carcinoma is a rare malignant tumor of the skin adnexa.
      While surgical resection is a treatment of choice in localized disease, frequent
      recurrence and distant metastasis make treatment difficult. Moreover, due to its
      rarity, optimal systemic treatment has not been determined. CASE REPORT A 59-year
      old female presented with disseminated subcutaneous nodules. Past history
      indicated she received repeated surgery, radiation therapy, and fluorouracil
      based systemic chemotherapy for recurrent sebaceous carcinoma. Following a
      subcutaneous nodule biopsy, histopathologic examination confirmed recurrent
      metastasis of sebaceous carcinoma. Because there was no established regimen as
      salvage chemotherapy, we decided to administer paclitaxel plus Adriamycin as a
      combination regimen after a thorough search of previous reports on PubMed. After
      the patient received 6 cycles of chemotherapy, all masses dramatically regressed.
      Unfortunately, several new lesions appeared 3 months after cessation of
      chemotherapy. Therefore, she was treated with anti-HGF antibody through a
      clinical trial. After that, she received nivolumab. But treatment with all the
      new agents did not show any response. Furthermore, her disease progressed
      rapidly. We re-challenged with the paclitaxel and Adriamycin regimen, 2 cycles of
      chemotherapy, and the follow-up positron emission tomography - computed
      tomography revealed marked decrement of multiple metastatic nodules. CONCLUSIONS
      Although several clinical reports have shown the effectiveness of fluorouracil,
      especially 5-fluorouracil-based chemotherapy, there has been a paucity of reports
      on other chemotherapeutic agents. We report a case of metastatic sebaceous
      carcinoma which showed favorable response to non-fluorouracil-based chemotherapy.

PMID- 30291223
TI  - The impact of lenalidomide exposure on response and outcomes in patients with
      lower-risk myelodysplastic syndromes and del(5q).

PMID- 30291224
TI  - IL-17A-associated IKK-alpha signaling induced TSLP production in epithelial cells
      of COPD patients.
AB  - Thymic stromal lymphopoietin (TSLP) is a cytokine expressed in the epithelium,
      involved in the pathogenesis of chronic disease. IL-17A regulates airway
      inflammation, oxidative stress, and reduction of steroid sensitivity in chronic
      obstructive pulmonary disease (COPD). TSLP and IL-17A were measured in induced
      sputum supernatants (ISs) from healthy controls (HC), healthy smokers (HS), and
      COPD patients by enzyme-linked immunosorbent assay. Human bronchial epithelial
      cell line (16HBE) and normal bronchial epithelial cells were stimulated with rhIL
      17A or ISs from COPD patients to evaluate TSLP protein and mRNA expression. The
      effects of the depletion of IL-17A in ISs, an anticholinergic drug, and the
      silencing of inhibitor kappa kinase alpha (IKKalpha) on TSLP production were
      evaluated in 16HBE cells. Coimmunoprecipitation of acetyl-histone
      H3(Lys14)/IKKalpha was evaluated in 16HBE cells treated with rhIL-17A and in the
      presence of the drug. TSLP and IL-17A levels were higher in ISs from COPD
      patients and HS compared with HC. TSLP protein and mRNA increased in 16HBE cells
      and in normal bronchial epithelial cells stimulated with ISs from COPD patients
      compared with ISs from HC and untreated cells. IKKalpha silencing reduced TSLP
      production in 16HBE cells stimulated with rhIL-17A and ISs from COPD patients.
      RhIL-17A increased the IKKalpha/acetyl-histone H3 immunoprecipitation in 16HBE
      cells. The anticholinergic drug affects TSLP protein and mRNA levels in bronchial
      epithelial cells treated with rhIL-17A or with ISs from COPD patients, and
      IKKalpha mediated acetyl-histone H3(Lys14). IL-17A/IKKalpha signaling induced the
      mechanism of chromatin remodeling associated with acetyl-histone H3(Lys14) and
      TSLP production in bronchial epithelial cells. Anticholinergic drugs might target
      TSLP derived from epithelial cells during the treatment of COPD.

PMID- 30291226
TI  - Response to Sachdeva et al: Brain Fogginess and SIBO Is Not a Mirage.

PMID- 30291225
TI  - A novel rat model of comorbid PTSD and addiction reveals intersections between
      stress susceptibility and enhanced cocaine seeking with a role for mGlu5
      receptors.
AB  - PTSD is highly comorbid with cocaine use disorder (CUD), and cocaine users with
      PTSD + CUD are more resistant to treatment. Here we sought to develop a rat model
      of PTSD + CUD in order to identify the neurobiological changes underlying such
      comorbidity and screen potential medications for reducing cocaine seeking in the
      PTSD population. We utilized a predator scent stress model of PTSD, wherein rats
      received a single exposure to the fox pheromone 2,5-dihydro-2,4,5
      trimethylthiazoline (TMT). One week after TMT exposure, stress-susceptible
      (susceptible), intermediate, and resilient phenotypes were detected and were
      consistent with behavioral, corticosterone, and gene expression profiles 3 weeks
      post TMT. We assessed phenotypic differences in cocaine self-administration,
      extinction, and cue-primed reinstatement. Susceptible rats exhibited deficits in
      extinction learning and increased cue-primed reinstatement that was not prevented
      by Ceftriaxone, an antibiotic that consistently attenuates the reinstatement of
      cocaine seeking. TMT-exposed resilient rats displayed increased mGlu5 gene
      expression in the amygdala and medial prefrontal cortex and did not display the
      enhanced cocaine seeking observed in susceptible rats. Combined treatment with
      the mGlu5 positive allosteric modulator 3-Cyano-N-(1,3-diphenyl-1 H-pyrazol-5
      yl)benzamide (CDPPB), fear extinction, and ceftriaxone prevented the
      reinstatement of cocaine seeking in susceptible rats with fear extinction an
      important mediating condition. These results highlight the need for animal models
      of PTSD to consider stress-responsivity, as only a subset of trauma-exposed
      individuals develop PTSD and these individuals likely exhibit distinct
      neurobiological changes compared with trauma-exposed populations who are
      resilient to stress. This work further identifies glutamate homeostasis and mGlu5
      as a target for treating relapse in comorbid PTSD-cocaine addiction.

PMID- 30291227
TI  - Evidence for magmatic carbon bias in 14C dating of the Taupo and other major
      eruptions.
AB  - Prehistoric timescales, volcanic hazard assessment, and understanding of
      volcanogenic climate events rely on accurate dating of prehistoric eruptions.
      Most late Quaternary eruptions are dated by 14C measurements on material from
      close to the volcano that may be contaminated by geologic-sourced infinite-age
      carbon. Here we show that 14C ages for the Taupo (New Zealand) First Millennium
      eruption are geographically arrayed, with oldest ages closer to the vent. The
      current eruption wiggle match date of 232 +/- 5 years CE is amongst the oldest.
      We present evidence that the older, vent-proximal 14C ages were biased by
      magmatic CO2 degassed from groundwater, and that the Taupo eruption occurred
      decades to two centuries after 232 CE. Our reinterpretation implies that ages for
      other proximally-dated, unobserved, eruptions may also be too old. Plateauing or
      declining tree ring cellulose delta13C and Delta14C values near a volcano
      indicate magmatic influence and may allow forecasting of super-eruptions.

PMID- 30291228
TI  - Powerful turbidity currents driven by dense basal layers.
AB  - Seafloor sediment flows (turbidity currents) are among the volumetrically most
      important yet least documented sediment transport processes on Earth. A scarcity
      of direct observations means that basic characteristics, such as whether flows
      are entirely dilute or driven by a dense basal layer, remain equivocal. Here we
      present the most detailed direct observations yet from oceanic turbidity
      currents. These powerful events in Monterey Canyon have frontal speeds of up to
      7.2 m s-1, and carry heavy (800 kg) objects at speeds of >=4 m s-1. We infer they
      consist of fast and dense near-bed layers, caused by remobilization of the
      seafloor, overlain by dilute clouds that outrun the dense layer. Seabed
      remobilization probably results from disturbance and liquefaction of loose-packed
      canyon-floor sand. Surprisingly, not all flows correlate with major perturbations
      such as storms, floods or earthquakes. We therefore provide a new view of
      sediment transport through submarine canyons into the deep-sea.

PMID- 30291229
TI  - Myelo-lymphoid lineage restriction occurs in the human haematopoietic stem cell
      compartment before lymphoid-primed multipotent progenitors.
AB  - Capturing where and how multipotency is lost is crucial to understand how blood
      formation is controlled. Blood lineage specification is currently thought to
      occur downstream of multipotent haematopoietic stem cells (HSC). Here we show
      that, in human, the first lineage restriction events occur within the CD19
      CD34+CD38-CD45RA-CD49f+CD90+ (49f+) HSC compartment to generate myelo-lymphoid
      committed cells with no erythroid differentiation capacity. At single-cell
      resolution, we observe a continuous but polarised organisation of the 49f+
      compartment, where transcriptional programmes and lineage potential progressively
      change along a gradient of opposing cell surface expression of CLEC9A and CD34.
      CLEC9AhiCD34lo cells contain long-term repopulating multipotent HSCs with slow
      quiescence exit kinetics, whereas CLEC9AloCD34hi cells are restricted to myelo
      lymphoid differentiation and display infrequent but durable repopulation
      capacity. We thus propose that human HSCs gradually transition to a discrete
      lymphoid-primed state, distinct from lymphoid-primed multipotent progenitors,
      representing the earliest entry point into lymphoid commitment.

PMID- 30291230
TI  - Direct electrical quantification of glucose and asparagine from bodily fluids
      using nanopores.
AB  - Crucial steps in the miniaturisation of biosensors are the conversion of a
      biological signal into an electrical current as well as the direct sampling of
      bodily fluids. Here we show that protein sensors in combination with a nanopore,
      acting as an electrical transducer, can accurately quantify metabolites in real
      time directly from nanoliter amounts of blood and other bodily fluids.
      Incorporation of the nanopore into portable electronic devices will allow
      developing sensitive, continuous, and non-invasive sensors for metabolites for
      point-of-care and home diagnostics.

PMID- 30291231
TI  - Self-induced mechanical stress can trigger biofilm formation in uropathogenic
      Escherichia coli.
AB  - Bacterial biofilms represent an important medical problem; however, the
      mechanisms of the onset of biofilm formation are poorly understood. Here, using
      new controlled methods allowing high-throughput and reproducible biofilm growth,
      we show that biofilm formation is linked to self-imposed mechanical stress. In
      growing uropathogenic Escherichia coli colonies, we report that mechanical stress
      can initially emerge from the physical stress accompanying colony confinement
      within micro-cavities or hydrogel environments reminiscent of the cytosol of host
      cells. Biofilm formation can then be enhanced by a nutrient access-modulated
      feedback loop, in which biofilm matrix deposition can be particularly high in
      areas of increased mechanical and biological stress, with the deposited matrix
      further enhancing the stress levels. This feedback regulation can lead to
      adaptive and diverse biofilm formation guided by the environmental stresses. Our
      results suggest previously unappreciated mechanisms of the onset and progression
      of biofilm growth.

PMID- 30291232
TI  - Gender effect on phenotype and genotype in patients with post-polycythemia vera
      and post-essential thrombocythemia myelofibrosis: results from the MYSEC project.

PMID- 30291234
TI  - Genome mining of cyclodipeptide synthases unravels unusual tRNA-dependent
      diketopiperazine-terpene biosynthetic machinery.
AB  - Cyclodipeptide synthases (CDPSs) can catalyze the formation of two successive
      peptide bonds by hijacking aminoacyl-tRNAs from the ribosomal machinery resulting
      in diketopiperazines (DKPs). Here, three CDPS-containing loci (dmt1-3) are
      discovered by genome mining and comparative genome analysis of Streptomyces
      strains. Among them, CDPS DmtB1, encoded by the gene of dmt1 locus, can
      synthesize cyclo(L-Trp-L-Xaa) (with Xaa being Val, Pro, Leu, Ile, or Ala).
      Systematic mutagenesis experiments demonstrate the importance of the residues
      constituting substrate-binding pocket P1 for the incorporation of the second aa
      tRNA in DmtB1. Characterization of dmt1-3 unravels that CDPS-dependent machinery
      is involved in CDPS-synthesized DKP formation followed by tailoring steps of
      prenylation and cyclization to afford terpenylated DKP compounds drimentines. A
      phytoene-synthase-like family prenyltransferase (DmtC1) and a membrane terpene
      cyclase (DmtA1) are required for drimentines biosynthesis. These results set the
      foundation for further increasing the natural diversity of complex DKP
      derivatives.

PMID- 30291233
TI  - A rapid rate of sex-chromosome turnover and non-random transitions in true frogs.
AB  - The canonical model of sex-chromosome evolution predicts that, as recombination
      is suppressed along sex chromosomes, gametologs will progressively differentiate,
      eventually becoming heteromorphic. However, there are numerous examples of
      homomorphic sex chromosomes across the tree of life. This homomorphy has been
      suggested to result from frequent sex-chromosome turnovers, yet we know little
      about which forces drive them. Here, we describe an extremely fast rate of
      turnover among 28 species of Ranidae. Transitions are not random, but converge on
      several chromosomes, potentially due to genes they harbour. Transitions also
      preserve the ancestral pattern of male heterogamety, in line with the 'hot
      potato' model of sex-chromosome transitions, suggesting a key role for mutation
      load accumulation in non-recombining genomic regions. The importance of mutation
      load selection in frogs might result from the extreme heterochiasmy they exhibit,
      making frog sex chromosomes differentiate immediately from emergence and across
      their entire length.

PMID- 30291235
TI  - Latitude-dependent finescale turbulent shear generations in the Pacific tropical
      extratropical upper ocean.
AB  - Turbulent mixing, which is critically important for the equilibrium of ocean
      circulation, is controlled by finescale turbulent shear (S2) of oceanic flows
      through shear instability. Although the relationship between S2 and mixing is
      well understood, the latitude-dependent generation processes of S2 remain poorly
      known due to the lack of geographically extensive, long-term finescale velocity
      measurements. Here, using one-year ADCP data from 17 moorings along 143 degrees
      E, we first show that the upper-ocean S2 and its resultant mixing rate have a W
      shaped latitudinal distribution in the tropical-extratropical northwest Pacific
      with peaks at 0-2 degrees N, 12-14 degrees N, and 20-22 degrees N, respectively.
      Further analyses reveal that these S2 peaks are caused by vertically-sheared
      equatorial currents, parametric subharmonic instability of diurnal tide, and
      anticyclonic eddy's inertial chimney effect, respectively. As climate model
      simulations are sensitive to the mixing parameterizations, our findings highlight
      the need to incorporate the latitude-dependent generation mechanisms of S2 to
      improve climate models' prediction capabilities.

PMID- 30291236
TI  - Bone protection by inhibition of microRNA-182.
AB  - Targeting microRNAs recently shows significant therapeutic promise; however, such
      progress is underdeveloped in treatment of skeletal diseases with osteolysis,
      such as osteoporosis and rheumatoid arthritis (RA). Here, we identified miR-182
      as a key osteoclastogenic regulator in bone homeostasis and diseases. Myeloid
      specific deletion of miR-182 protects mice against excessive osteoclastogenesis
      and bone resorption in disease models of ovariectomy-induced osteoporosis and
      inflammatory arthritis. Pharmacological treatment of these diseases with miR-182
      inhibitors completely suppresses pathologic bone erosion. Mechanistically, we
      identify protein kinase double-stranded RNA-dependent (PKR) as a new and
      essential miR-182 target that is a novel inhibitor of osteoclastogenesis via
      regulation of the endogenous interferon (IFN)-beta-mediated autocrine feedback
      loop. The expression levels of miR-182, PKR, and IFN-beta are altered in RA and
      are significantly correlated with the osteoclastogenic capacity of RA monocytes.
      Our findings reveal a previously unrecognized regulatory network mediated by miR
      182-PKR-IFN-beta axis in osteoclastogenesis, and highlight the therapeutic
      implications of miR-182 inhibition in osteoprotection.

PMID- 30291237
TI  - Targeting of NLRP3 inflammasome with gene editing for the amelioration of
      inflammatory diseases.
AB  - The NLRP3 inflammasome is a well-studied target for the treatment of multiple
      inflammatory diseases, but how to promote the current therapeutics remains a
      large challenge. CRISPR/Cas9, as a gene editing tool, allows for direct ablation
      of NLRP3 at the genomic level. In this study, we screen an optimized cationic
      lipid-assisted nanoparticle (CLAN) to deliver Cas9 mRNA (mCas9) and guide RNA
      (gRNA) into macrophages. By using CLAN encapsulating mCas9 and gRNA-targeting
      NLRP3 (gNLRP3) (CLANmCas9/gNLRP3), we disrupt NLRP3 of macrophages, inhibiting
      the activation of the NLRP3 inflammasome in response to diverse stimuli. After
      intravenous injection, CLANmCas9/gNLRP3 mitigates acute inflammation of LPS
      induced septic shock and monosodium urate crystal (MSU)-induced peritonitis. In
      addition, CLANmCas9/gNLRP3 treatment improves insulin sensitivity and reduces
      adipose inflammation of high-fat-diet (HFD)-induced type 2 diabetes (T2D). Thus,
      our study provides a promising strategy for treating NLRP3-dependent inflammatory
      diseases and provides a carrier for delivering CRISPR/Cas9 into macrophages.

PMID- 30291238
TI  - Structural properties of a haemophore facilitate targeted elimination of the
      pathogen Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is a keystone bacterial pathogen of chronic
      periodontitis. P. gingivalis is unable to synthesise the porphyrin macrocycle and
      relies on exogenous porphyrin, including haem or haem biosynthesis intermediates
      from host sources. We show that under the iron-limited conditions prevailing in
      tissue environments, P. gingivalis expresses a haemophore-like protein, HusA, to
      mediate the uptake of essential porphyrin and support pathogen survival within
      epithelial cells. The structure of HusA, together with titration studies,
      mutagenesis and in silico docking, show that haem binds in a hydrophobic groove
      on the alpha-helical structure without the typical iron coordination seen in
      other haemophores. This mode of interaction allows HusA to bind to a variety of
      abiotic and metal-free porphyrins with higher affinities than to haem. We exploit
      this unusual porphyrin-binding activity of HusA to target a prototypic
      deuteroporphyrin-metronidazole conjugate with restricted antimicrobial
      specificity in a Trojan horse strategy that effectively kills intracellular P.
      gingivalis.

PMID- 30291239
TI  - Nickel nanoparticles set a new record of strength.
AB  - Material objects with micrometer or nanometer dimensions can exhibit much higher
      strength than macroscopic objects, but this strength rarely approaches the
      maximum theoretical strength of the material. Here, we demonstrate that faceted
      single-crystalline nickel (Ni) nanoparticles exhibit an ultrahigh compressive
      strength (up to 34 GPa) unprecedented for metallic materials. This strength
      matches the available estimates of Ni theoretical strength. Three factors are
      responsible for this record-high strength: the large Ni shear modulus, the smooth
      edges and corners of the nanoparticles, and the thin oxide layer on the particle
      surface. This finding is supported by molecular dynamics simulations that closely
      mimic the experimental conditions, which show that the mechanical failure of the
      strongest particles is triggered by homogeneous nucleation of dislocation loops
      inside the particle. The nucleation of a stable loop is preceded by multiple
      nucleation attempts accompanied by unusually large local atomic displacements
      caused by thermal fluctuations.

PMID- 30291240
TI  - Electrophysiological mechanisms of human memory consolidation.
AB  - Consolidation stabilizes memory traces after initial encoding. Rodent studies
      suggest that memory consolidation depends on replay of stimulus-specific activity
      patterns during fast hippocampal "ripple" oscillations. Here, we measured replay
      in intracranial electroencephalography recordings in human epilepsy patients, and
      related replay to ripples. Stimulus-specific activity was identified using
      representational similarity analysis and then tracked during waking rest and
      sleep after encoding. Stimulus-specific gamma (30-90 Hz) activity during early
      (100-500 ms) and late (500-1200 ms) encoding is spontaneously reactivated during
      waking state and sleep, independent of later memory. Ripples during nREM sleep,
      but not during waking state, trigger replay of activity from the late time window
      specifically for remembered items. Ripple-triggered replay of activity from the
      early time window during nREM sleep is enhanced for forgotten items. These
      results provide the first electrophysiological evidence for replay related to
      memory consolidation in humans, and point to a prominent role of nREM ripple
      triggered replay in consolidation processes.

PMID- 30291242
TI  - Orthogonal programming of heterogeneous micro-mechano-environments and geometries
      in three-dimensional bio-stereolithography.
AB  - Engineering heterogeneous micro-mechano-microenvironments of extracellular matrix
      is of great interest in tissue engineering, but spatial control over mechanical
      heterogeneity in three dimensions is still challenging given the fact that
      geometry and stiffness are inherently intertwined in fabrication. Here, we
      develop a layer-by-layer three-dimensional (3D) printing paradigm which achieves
      orthogonal control of stiffness and geometry by capitalizing on the
      conventionally adverse effect of oxygen inhibition on free-radical
      polymerization. Controlled oxygen permeation and inhibition result in photo-cured
      hydrogel layers with thicknesses only weakly dependent to the ultraviolet
      exposure dosage. The dosage is instead leveraged to program the crosslink density
      and stiffness of the cured structures. The programmable stiffness spans nearly an
      order of magnitude (E ~ 2-15 kPa) within the physiologically relevant range. We
      further demonstrate that extracellular matrices with programmed micro-mechano
      environments can dictate 3D cellular organization, enabling in vitro tissue
      reconstruction.

PMID- 30291241
TI  - Copy number load predicts outcome of metastatic colorectal cancer patients
      receiving bevacizumab combination therapy.
AB  - Increased copy number alterations (CNAs) indicative of chromosomal instability
      (CIN) have been associated with poor cancer outcome. Here, we study CNAs as
      potential biomarkers of bevacizumab (BVZ) response in metastatic colorectal
      cancer (mCRC). We cluster 409 mCRCs in three subclusters characterized by
      different degrees of CIN. Tumors belonging to intermediate-to-high instability
      clusters have improved outcome following chemotherapy plus BVZ versus
      chemotherapy alone. In contrast, low instability tumors, which amongst others
      consist of POLE-mutated and microsatellite-instable tumors, derive no further
      benefit from BVZ. This is confirmed in 81 mCRC tumors from the phase 2 MoMa study
      involving BVZ. CNA clusters overlap with CRC consensus molecular subtypes (CMS);
      CMS2/4 xenografts correspond to intermediate-to-high instability clusters and
      respond to FOLFOX chemotherapy plus mouse avastin (B20), while CMS1/3 xenografts
      match with low instability clusters and fail to respond. Overall, we identify
      copy number load as a novel potential predictive biomarker of BVZ combination
      therapy.

PMID- 30291243
TI  - High-performance nanomaterials formed by rigid yet extensible cyclic beta-peptide
      polymers.
AB  - Organisms have evolved biomaterials with an extraordinary convergence of high
      mechanical strength, toughness, and elasticity. In contrast, synthetic materials
      excel in stiffness or extensibility, and a combination of the two is necessary to
      exceed the performance of natural biomaterials. We bridge this materials property
      gap through the side-chain-to-side-chain polymerization of cyclic beta-peptide
      rings. Due to their strong dipole moments, the rings self-assemble into rigid
      nanorods, stabilized by hydrogen bonds. Displayed amines serve as
      functionalization sites, or, if protonated, force the polymer to adopt an
      unfolded conformation. This molecular design enhances the processability and
      extensibility of the biopolymer. Molecular dynamics simulations predict stick
      slip deformations dissipate energy at large strains, thereby, yielding toughness
      values greater than natural silks. Moreover, the synthesis route can be adapted
      to alter the dimensions and displayed chemistries of nanomaterials with
      mechanical properties that rival nature.

PMID- 30291244
TI  - Lateral inhibition by Martinotti interneurons is facilitated by cholinergic
      inputs in human and mouse neocortex.
AB  - A variety of inhibitory pathways encompassing different interneuron types shape
      activity of neocortical pyramidal neurons. While basket cells (BCs) mediate fast
      lateral inhibition between pyramidal neurons, Somatostatin-positive Martinotti
      cells (MCs) mediate a delayed form of lateral inhibition. Neocortical circuits
      are under control of acetylcholine, which is crucial for cortical function and
      cognition. Acetylcholine modulates MC firing, however, precisely how cholinergic
      inputs affect cortical lateral inhibition is not known. Here, we find that
      cholinergic inputs selectively augment and speed up lateral inhibition between
      pyramidal neurons mediated by MCs, but not by BCs. Optogenetically activated
      cholinergic inputs depolarize MCs through activation of beta2 subunit-containing
      nicotinic AChRs, not muscarinic AChRs, without affecting glutamatergic inputs to
      MCs. We find that these mechanisms are conserved in human neocortex. Cholinergic
      inputs thus enable cortical pyramidal neurons to recruit more MCs, and can
      thereby dynamically highlight specific circuit motifs, favoring MC-mediated
      pathways over BC-mediated pathways.

PMID- 30291245
TI  - Suppressor mutations in Rpf2-Rrs1 or Rpl5 bypass the Cgr1 function for pre
      ribosomal 5S RNP-rotation.
AB  - During eukaryotic 60S biogenesis, the 5S RNP requires a large rotational movement
      to achieve its mature position. Cryo-EM of the Rix1-Rea1 pre-60S particle has
      revealed the post-rotation stage, in which a gently undulating alpha-helix
      corresponding to Cgr1 becomes wedged between Rsa4 and the relocated 5S RNP, but
      the purpose of this insertion was unknown. Here, we show that cgr1 deletion in
      yeast causes a slow-growth phenotype and reversion of the pre-60S particle to the
      pre-rotation stage. However, spontaneous extragenic suppressors could be
      isolated, which restore growth and pre-60S biogenesis in the absence of Cgr1.
      Whole-genome sequencing reveals that the suppressor mutations map in the Rpf2
      Rrs1 module and Rpl5, which together stabilize the unrotated stage of the 5S RNP.
      Thus, mutations in factors stabilizing the pre-rotation stage facilitate 5S RNP
      relocation upon deletion of Cgr1, but Cgr1 itself could stabilize the post
      rotation stage.

PMID- 30291246
TI  - Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin
      nanoparticles enables successful vector re-administration.
AB  - Gene therapy mediated by recombinant adeno-associated virus (AAV) vectors is a
      promising treatment for systemic monogenic diseases. However, vector
      immunogenicity represents a major limitation to gene transfer with AAV vectors,
      particularly for vector re-administration. Here, we demonstrate that synthetic
      vaccine particles encapsulating rapamycin (SVP[Rapa]), co-administered with AAV
      vectors, prevents the induction of anti-capsid humoral and cell-mediated
      responses. This allows successful vector re-administration in mice and nonhuman
      primates. SVP[Rapa] dosed with AAV vectors reduces B and T cell activation in an
      antigen-selective manner, inhibits CD8+ T cell infiltration in the liver, and
      efficiently blocks memory T cell responses. SVP[Rapa] immunomodulatory effects
      can be transferred from treated to naive mice by adoptive transfer of
      splenocytes, and is inhibited by depletion of CD25+ T cells, suggesting a role
      for regulatory T cells. Co-administration of SVP[Rapa] with AAV vector represents
      a powerful strategy to modulate vector immunogenicity and enable effective vector
      re-administration.

PMID- 30291247
TI  - Graphene-enabled and directed nanomaterial placement from solution for large
      scale device integration.
AB  - Directed placement of solution-based nanomaterials at predefined locations with
      nanoscale precision limits bottom-up integration in semiconductor process
      technology. We report a method for electric-field-assisted placement of
      nanomaterials from solution by means of large-scale graphene layers featuring
      nanoscale deposition sites. The structured graphene layers are prepared via
      either transfer or synthesis on standard substrates, and then are removed once
      nanomaterial deposition is completed, yielding material assemblies with nanoscale
      resolution that cover surface areas >1 mm2. In order to demonstrate the broad
      applicability, we have assembled representative zero-dimensional, one
      dimensional, and two-dimensional semiconductors at predefined substrate locations
      and integrated them into nanoelectronic devices. Ultimately, this method opens a
      route to bottom-up integration of nanomaterials for industry-scale applications.

PMID- 30291248
TI  - Thermal and electrical signatures of a hydrodynamic electron fluid in tungsten
      diphosphide.
AB  - In stark contrast to ordinary metals, in materials in which electrons strongly
      interact with each other or with phonons, electron transport is thought to
      resemble the flow of viscous fluids. Despite their differences, it is predicted
      that transport in both conventional and correlated materials is fundamentally
      limited by the uncertainty principle applied to energy dissipation. Here we
      report the observation of experimental signatures of hydrodynamic electron flow
      in the Weyl semimetal tungsten diphosphide. Using thermal and magneto-electric
      transport experiments, we find indications of the transition from a conventional
      metallic state at higher temperatures to a hydrodynamic electron fluid below 20
      K. The hydrodynamic regime is characterized by a viscosity-induced dependence of
      the electrical resistivity on the sample width and by a strong violation of the
      Wiedemann-Franz law. Following the uncertainty principle, both electrical and
      thermal transport are bound by the quantum indeterminacy, independent of the
      underlying transport regime.

PMID- 30291249
TI  - Bright room temperature single photon source at telecom range in cubic silicon
      carbide.
AB  - Single-photon emitters (SPEs) play an important role in a number of quantum
      information tasks such as quantum key distributions. In these protocols, telecom
      wavelength photons are desired due to their low transmission loss in optical
      fibers. In this paper, we present a study of bright single-photon emitters in
      cubic silicon carbide (3C-SiC) emitting in the telecom range. We find that these
      emitters are photostable and bright at room temperature with a count rate of ~
      MHz. Altogether with the fact that SiC is a growth and fabrication-friendly
      material, our result may be relevant for future applications in quantum
      communication technology.

PMID- 30291250
TI  - Dynamic intercellular transport modulates the spatial patterning of
      differentiation during early neural commitment.
AB  - The initiation of heterogeneity within a population of phenotypically identical
      progenitors is a critical event for the onset of morphogenesis and
      differentiation patterning. Gap junction communication within multicellular
      systems produces complex networks of intercellular connectivity that result in
      heterogeneous distributions of intracellular signaling molecules. In this study,
      we investigate emergent systems-level behavior of the intercellular network
      within embryonic stem cell (ESC) populations and corresponding spatial
      organization during early neural differentiation. An agent-based model
      incorporates experimentally-determined parameters to yield complex transport
      networks for delivery of pro-differentiation cues between neighboring cells,
      reproducing the morphogenic trajectories during retinoic acid-accelerated mouse
      ESC differentiation. Furthermore, the model correctly predicts the delayed
      differentiation and preserved spatial features of the morphogenic trajectory that
      occurs in response to intercellular perturbation. These findings suggest an
      integral role of gap junction communication in the temporal coordination of
      emergent patterning during early differentiation and neural commitment of
      pluripotent stem cells.

PMID- 30291251
TI  - Testicular cancer.
AB  - Testicular cancer is the most common malignancy among men between 14 and 44 years
      of age, and its incidence has risen over the past two decades in Western
      countries. Both genetic and environmental factors contribute to the development
      of testicular cancer, for which cryptorchidism is the most common risk factor.
      Progress has been made in our understanding of the disease since the initial
      description of carcinoma in situ of the testis in 1972 (now referred to as germ
      cell neoplasia in situ), which has led to improved treatment options. The
      combination of surgery and cisplatin-based chemotherapy has resulted in a cure
      rate of >90% in patients with testicular cancer, although some patients become
      refractory to chemotherapy or have a late relapse; an improved understanding of
      the molecular determinants underlying tumour sensitivity and resistance may lead
      to the development of novel therapies for these patients. This Primer provides an
      overview of the biology, epidemiology, diagnosis and current treatment guidelines
      for testicular cancer, with a focus on germ cell tumours. We also outline areas
      for future research and what to expect in the next decade for testicular cancer.

PMID- 30291254
TI  - Testicular cancer.

PMID- 30291252
TI  - Aberrant expression of CITED2 promotes prostate cancer metastasis by activating
      the nucleolin-AKT pathway.
AB  - Despite many efforts to develop hormone therapy and chemotherapy, no effective
      strategy to suppress prostate cancer metastasis has been established because the
      metastasis is not well understood. We here investigate a role of CBP/p300
      interacting transactivator with E/D-rich carboxy-terminal domain-2 (CITED2) in
      prostate cancer metastasis. CITED2 is highly expressed in metastatic prostate
      cancer, and its expression is correlated with poor survival. The CITED2 gene is
      highly activated by ETS-related gene that is overexpressed due to chromosomal
      translocation. CITED2 acts as a molecular chaperone to guide PRMT5 and p300 to
      nucleolin, thereby activating nucleolin. Informatics and experimental data
      suggest that the CITED2-nucleolin axis is involved in prostate cancer metastasis.
      This axis stimulates cell migration through the epithelial-mesenchymal transition
      and promotes cancer metastasis in a xenograft mouse model. Our results suggest
      that CITED2 plays a metastasis-promoting role in prostate cancer and thus could
      be a target for preventing prostate cancer metastasis.

PMID- 30291253
TI  - Intestinal microbiome adjusts the innate immune setpoint during colonization
      through negative regulation of MyD88.
AB  - Host pathways mediating changes in immune states elicited by intestinal microbial
      colonization are incompletely characterized. Here we describe alterations of the
      host immune state induced by colonization of germ-free zebrafish larvae with an
      intestinal microbial community or single bacterial species. We show that
      microbiota-induced changes in intestinal leukocyte subsets and whole-body host
      gene expression are dependent on the innate immune adaptor gene myd88. Similar
      patterns of gene expression are elicited by colonization with conventional
      microbiome, as well as mono-colonization with two different zebrafish commensal
      bacterial strains. By studying loss-of-function myd88 mutants, we find that
      colonization suppresses Myd88 at the mRNA level. Tlr2 is essential for microbiota
      induced effects on myd88 transcription and intestinal immune cell composition.

PMID- 30291255
TI  - The Quantum Mechanics of a Rolling Molecular "Nanocar".
AB  - We formulate a mathematical model of a rolling "molecular wheelbarrow"-a two
      wheeled nanoscale molecular machine-informed by experiments on molecular machines
      recently synthesized in labs. The model is a nonholonomic system (briefly, a
      system with non-integrable velocity constraints), for which no general
      quantization procedure exists. Nonetheless, we successfully embed the system in a
      Hamiltonian one and then quantize the result using geometric quantization and
      other tools; we extract from the result the quantum mechanics of the molecular
      wheelbarrow, and derive explicit formulae for the quantized energy spectrum. We
      also study a few variants of our model, some of which ignore the model's
      nonholonomic constraints. We show that these variants have different quantum
      energy spectra, indicating that in such systems one should not ignore the
      nonholonomic constraints, since they alter in a non-trivial way the energy
      spectrum of the molecule.

PMID- 30291256
TI  - A genomic Neolithic time transect of hunter-farmer admixture in central Poland.
AB  - Ancient DNA genome-wide analyses of Neolithic individuals from central and
      southern Europe indicate an overall population turnover pattern in which
      migrating farmers from Anatolia and the Near East largely replaced autochthonous
      Mesolithic hunter-gatherers. However, the genetic history of the Neolithic
      transition in areas lying north of the European Neolithic core region involved
      different levels of admixture with hunter-gatherers. Here we analyse genome-wide
      data of 17 individuals spanning from the Middle Neolithic to the Early Bronze Age
      (4300-1900 BCE) in order to assess the Neolithic transition in north-central
      Poland, and the local impacts of hunter-farmer contacts and Late Neolithic steppe
      migrations. We evaluate the influence of these on local populations and assess if
      and how they change through time, reporting evidence of recurrent hunter-farmer
      admixture over three millennia, and the co-existence of unadmixed hunter
      gatherers as late as 4300 BCE. During the Late Neolithic we report the appearance
      of steppe ancestry, but on a lesser scale than previously described for other
      central European regions, with evidence of stronger affinities to hunter
      gatherers than to steppe pastoralists. These results help understand the
      Neolithic palaeogenomics of another central European area, Kuyavia, and highlight
      the complexity of population interactions during those times.

PMID- 30291257
TI  - VOC breath profile in spontaneously breathing awake swine during Influenza A
      infection.
AB  - Influenza is one of the most common causes of virus diseases worldwide. Virus
      detection requires determination of Influenza RNA in the upper respiratory tract.
      Efficient screening is not possible in this way. Analysis of volatile organic
      compounds (VOCs) in breath holds promise for non-invasive and fast monitoring of
      disease progression. Breath VOC profiles of 14 (3 controls and 11 infected
      animals) swine were repeatedly analyzed during a complete infection cycle of
      Influenza A under high safety conditions. Breath VOCs were pre-concentrated by
      means of needle trap micro-extraction and analysed by gas chromatography mass
      spectrometry before infection, during virus presence in the nasal cavity, and
      after recovery. Six VOCs could be related to disease progression: acetaldehyde,
      propanal, n-propyl acetate, methyl methacrylate, styrene and 1,1
      dipropoxypropane. As early as on day four after inoculation, when animals were
      tested positive for Influenza A, differentiation between control and infected
      animals was possible. VOC based information on virus infection could enable early
      detection of Influenza A. As VOC analysis is completely non-invasive it has
      potential for large scale screening purposes. In a perspective, breath analysis
      may offer a novel tool for Influenza monitoring in human medicine, animal health
      control or border protection.

PMID- 30291258
TI  - Oleoylethanolamide treatment affects gut microbiota composition and the
      expression of intestinal cytokines in Peyer's patches of mice.
AB  - The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of
      peroxisome proliferator-activated receptor-alpha (PPAR-alpha) secreted in the
      proximal intestine, is endowed with several distinctive homeostatic properties,
      such as control of appetite, anti-inflammatory activity, stimulation of lipolysis
      and fatty acid oxidation. When administered exogenously, OEA has beneficial
      effects in several cognitive paradigms; therefore, in all respects, OEA can be
      considered a hormone of the gut-brain axis. Here we report an unexplored
      modulatory effect of OEA on the intestinal microbiota and on immune response. Our
      study shows for the first time that sub-chronic OEA administration to mice fed a
      normal chow pellet diet, changes the faecal microbiota profile, shifting the
      Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular
      Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces
      intestinal cytokines expression by immune cells isolated from Peyer's patches.
      Our results suggest that sub-chronic OEA treatment modulates gut microbiota
      composition towards a "lean-like phenotype", and polarises gut-specific immune
      responses mimicking the effect of a diet low in fat and high in polysaccharides
      content.

PMID- 30291259
TI  - Aromatic thermosetting copolyester bionanocomposites as reconfigurable bone
      substitute materials: Interfacial interactions between reinforcement particles
      and polymer network.
AB  - Development of porous materials consisting of polymer host matrix enriched with
      bioactive ceramic particles that can initiate the reproduction of cellular
      organisms while maintaining in vivo mechanical reliability is a long-standing
      challenge for synthetic bone substitutes. We present hydroxyapatite (HA)
      reinforced aromatic thermosetting copolyester (ATSP) matrix bionanocomposite as a
      potential reconfigurable bone replacement material. The nanocomposite is
      fabricated by solid-state mixing a matching set of precursor oligomers with
      biocompatible pristine HA particles. During endothermic condensation
      polymerization reaction, the constituent oligomers form a mechanochemically
      robust crosslinked aromatic backbone while incorporating the HAs into a self
      generated cellular structure. The morphological analysis demonstrates near
      homogenous distributions of the pristine HAs within the matrix. The HAs behave as
      a crack-arrester which promotes a more deformation-tolerant formation with
      relatively enhanced material toughness. Chain relaxation dynamics of the
      nanocomposite matrix during glass transition is modified via HA-induced segmental
      immobilization. Chemical characterization of the polymer backbone composition
      reveals the presence of a hydrogen-advanced covalent interfacial coupling
      mechanism between the HAs and ATSP matrix. This report lays the groundwork for
      further studies on aromatic thermosetting copolyester matrix bionanocomposites
      which may find applications in various artificial bone needs.

PMID- 30291260
TI  - Epidemiology, microbiology and therapeutic consequences of chronic osteomyelitis
      in northern China: A retrospective analysis of 255 Patients.
AB  - The study aimed to explore the epidemiology and clinical characteristics of
      chronic osteomyelitis observed in a northern China hospital. Clinical data of 255
      patients with chronic osteomyelitis from January 2007 to January 2014 were
      collected and analyzed, including general information, disease data, treatment
      and follow-up data. Chronic osteomyelitis is more common in males and in the age
      group from 41-50 years of age. Common infection sites are the femur,
      tibiofibular, and hip joint. More g+ than g- bacterial infections were observed,
      with S. aureus the most commonly observed pathogenic organism. The positive
      detection rate from debridement bacterial culture is 75.6%. The detection rate
      when five samples are sent for bacterial culture is 90.6%, with pathogenic
      bacteria identified in 82.8% of cases. The two-stage debridement method (87.0%)
      has higher first curative rate than the one-stage debridement method (71.2%). To
      improve detection rate using bacterial culture, at least five samples are
      recommended. Treatment of chronic osteomyelitis with two-stage debridement, plus
      antibiotic-loaded polymethylmethacrylate (PMMA) beads provided good clinical
      results in this study and is therefore recommended.

PMID- 30291261
TI  - High Speed, High Density Intraoperative 3D Optical Topographical Imaging with
      Efficient Registration to MRI and CT for Craniospinal Surgical Navigation.
AB  - Intraoperative image-guided surgical navigation for craniospinal procedures has
      significantly improved accuracy by providing an avenue for the surgeon to
      visualize underlying internal structures corresponding to the exposed surface
      anatomy. Despite the obvious benefits of surgical navigation, surgeon adoption
      remains relatively low due to long setup and registration times, steep learning
      curves, and workflow disruptions. We introduce an experimental navigation system
      utilizing optical topographical imaging (OTI) to acquire the 3D surface anatomy
      of the surgical cavity, enabling visualization of internal structures relative to
      exposed surface anatomy from registered preoperative images. Our OTI approach
      includes near instantaneous and accurate optical measurement of >250,000 surface
      points, computed at >52,000 points-per-second for considerably faster patient
      registration than commercially available benchmark systems without compromising
      spatial accuracy. Our experience of 171 human craniospinal surgical procedures,
      demonstrated significant workflow improvement (41 s vs. 258 s and 794 s, p <
      0.05) relative to benchmark navigation systems without compromising surgical
      accuracy. Our advancements provide the cornerstone for widespread adoption of
      image guidance technologies for faster and safer surgeries without intraoperative
      CT or MRI scans. This work represents a major workflow improvement for navigated
      craniospinal procedures with possible extension to other image-guided
      applications.

PMID- 30291262
TI  - Pathological macromolecular crystallographic data affected by twinning, partial
      disorder and exhibiting multiple lattices for testing of data processing and
      refinement tools.
AB  - Twinning is a crystal growth anomaly, which has posed a challenge in
      macromolecular crystallography (MX) since the earliest days. Many approaches have
      been used to treat twinned data in order to extract structural information.
      However, in most cases it is usually simpler to rescreen for new crystallization
      conditions that yield an untwinned crystal form or, if possible, collect data
      from non-twinned parts of the crystal. Here, we report 11 structures of
      engineered variants of the E. coli enzyme N-acetyl-neuraminic lyase which,
      despite twinning and incommensurate modulation, have been successfully indexed,
      solved and deposited. These structures span a resolution range of 1.45-2.30 A,
      which is unusually high for datasets presenting such lattice disorders in MX and
      therefore these data provide an excellent test set for improving and challenging
      MX data processing programs.

PMID- 30291263
TI  - Machine-learning based lipid mediator serum concentration patterns allow
      identification of multiple sclerosis patients with high accuracy.
AB  - Based on increasing evidence suggesting that MS pathology involves alterations in
      bioactive lipid metabolism, the present analysis was aimed at generating a
      complex serum lipid-biomarker. Using unsupervised machine-learning, implemented
      as emergent self-organizing maps of neuronal networks, swarm intelligence and
      Minimum Curvilinear Embedding, a cluster structure was found in the input data
      space comprising serum concentrations of d = 43 different lipid-markers of
      various classes. The structure coincided largely with the clinical diagnosis,
      indicating that the data provide a basis for the creation of a biomarker
      (classifier). This was subsequently assessed using supervised machine-learning,
      implemented as random forests and computed ABC analysis-based feature selection.
      Bayesian statistics-based biomarker creation was used to map the diagnostic
      classes of either MS patients (n = 102) or healthy subjects (n = 301). Eight
      lipid-markers passed the feature selection and comprised GluCerC16, LPA20:4,
      HETE15S, LacCerC24:1, C16Sphinganine, biopterin and the endocannabinoids PEA and
      OEA. A complex classifier or biomarker was developed that predicted MS at a
      sensitivity, specificity and accuracy of approximately 95% in training and test
      data sets, respectively. The present successful application of serum lipid marker
      concentrations to MS data is encouraging for further efforts to establish an MS
      biomarker based on serum lipidomics.

PMID- 30291264
TI  - Unusual bidirectional frequency dependence of dynamical susceptibility in
      hexagonal intermetallic Pr2Ni0.95Si2.95.
AB  - In this study, the synthesis of a novel ternary intermetallic compound
      Pr2Ni0.95Si2.95 forming in single phase only by deliberately introducing
      vacancies in Ni/Si site is reported. The detailed studies on dc magnetization,
      heat capacity, ac magnetization & associated dynamical scaling, different types
      of non-equilibrium dynamical behaviour, viz., magnetic relaxation behaviour as a
      function of wait time and temperature, aging phenomena, and magnetic memory
      effect firmly establish that the compound exhibits spin freezing behaviour below
      3.3 K (Tf). However, below Tf, temperature dependence of ac susceptibility data
      exhibit an additional peak that shows reverse frequency dependence to that
      generally observed in a glassy system. The unusual bidirectional frequency
      dependence in a single magnetic system is of significant interest and rarely
      reported in literature. Competing exchange interaction arising from c/a ~ 1 and
      crystallographic randomness driven magnetic phase separation has been argued to
      be responsible for such observation. The reverse frequency shift of the low
      temperature peak has been described on the basis of a simple phenomenological
      model proposed in this work.

PMID- 30291265
TI  - Site-Specific Labelling of Multidomain Proteins by Amber Codon Suppression.
AB  - The access to information on the dynamic behaviour of large proteins is usually
      hindered as spectroscopic methods require the site-specific attachment of
      biophysical probes. A powerful emerging tool to tackle this issue is amber codon
      suppression. Till date, its application on large and complex multidomain proteins
      of MDa size has not been reported. Herein, we systematically investigate the
      feasibility to introduce different non-canonical amino acids into a 540 kDa
      homodimeric fatty acid synthase type I by genetic code expansion with subsequent
      fluorescent labelling. Our approach relies on a microplate-based reporter assay
      of low complexity using a GFP fusion protein to quickly screen for sufficient
      suppression conditions. Once identified, these findings were successfully
      utilized to upscale both the expression scale and the protein size to full-length
      constructs. These fluorescently labelled samples of fatty acid synthase were
      subjected to initial biophysical experiments, including HPLC analysis, activity
      assays and fluorescence spectroscopy. Successful introduction of such probes into
      a molecular machine such as fatty acid synthases may pave the way to understand
      the conformational variability, which is a primary intrinsic property required
      for efficient interplay of all catalytic functionalities, and to engineer them.

PMID- 30291266
TI  - Cytometry meets next-generation sequencing - RNA-Seq of sorted subpopulations
      reveals regional replication and iron-triggered prophage induction in
      Corynebacterium glutamicum.
AB  - Phenotypic diversification is key to microbial adaptation. Currently, advanced
      technological approaches offer insights into cell-to-cell variation of bacterial
      populations at a spatiotemporal resolution. However, the underlying molecular
      causes or consequences often remain obscure. In this study, we developed a
      workflow combining fluorescence-activated cell sorting and RNA-sequencing,
      thereby allowing transcriptomic analysis of 106 bacterial cells. As a proof of
      concept, the workflow was applied to study prophage induction in a subpopulation
      of Corynebacterium glutamicum. Remarkably, both the phage genes and flanking
      genomic regions of the CGP3 prophage revealed significantly increased coverage
      upon prophage induction - a phenomenon that to date has been obscured by bulk
      approaches. Genome sequencing of prophage-induced populations suggested regional
      replication at the CGP3 locus in C. glutamicum. Finally, the workflow was applied
      to unravel iron-triggered prophage induction in early exponential cultures. Here,
      an up-shift in iron levels resulted in a heterogeneous response of an SOS (PdivS)
      reporter. RNA-sequencing of the induced subpopulation confirmed induction of the
      SOS response triggering also activation of the CGP3 prophage. The fraction of
      CGP3-induced cells was enhanced in a mutant lacking the iron regulator DtxR
      suffering from enhanced iron uptake. Altogether, these findings demonstrate the
      potential of the established workflow to gain insights into the phenotypic
      dynamics of bacterial populations.

PMID- 30291267
TI  - Realizing multi-functional all-optical data processing on nanoscale SiC
      waveguides.
AB  - All-optical logics are realized on nanoscale SiC waveguides with add-drop micro
      ring functionality, including the TE/TM polarized data decoding, the dual-port
      Kerr switching and gating beyond 12 Gbit/s. With employing the C-C bond enriched
      SiC thin film upon thermal oxide, the nonlinear refractive index of up to 2.44 *
      10-12 cm2/W enables the asymmetric waveguide with polarization distinguishable
      transmission, which provides a polarization-selectivity to discreminate the TE/TM
      polarized data decoding with an nearly 9-dB extinction ratio. The TE/TM polarized
      decoding performance is comparable with a state-of-the-art fiberized in-line
      polarizer. The complementary transmission in the bus waveguide port facilitates
      the dual-port Kerr switching for data format conversion/inversion in both
      add/drop channels. Owing to the TE/TM polarization discriminated throughput, the
      asymmetric add-drop waveguide micro-ring also permits all-optical AND logic
      gating functions, where the ON-state outputs only if the pump bit is set at ON
      state and the probe bit with matched polarization. These results reveal the multi
      functionality of the nanoscale SiC add-drop micro-ring waveguide for future
      photonic logics on chip.

PMID- 30291268
TI  - Technology Transfer of the Microphysiological Systems: A Case Study of the Human
      Proximal Tubule Tissue Chip.
AB  - The adoption of a new technology into basic research, and industrial and clinical
      settings requires rigorous testing to build confidence in the reproducibility,
      reliability, robustness, and relevance of these models. Tissue chips are
      promising new technology, they have the potential to serve as a valuable tool in
      biomedical research, as well as pharmaceutical development with regards to
      testing for efficacy and safety. The principal goals of this study were to
      validate a previously established proximal tubule tissue chip model in an
      independent laboratory and to extend its utility to testing of nephrotoxic
      compounds. Here, we evaluated critical endpoints from the tissue chip developer
      laboratory, focusing on biological relevance (long-term viability, baseline
      protein and gene expression, ammoniagenesis, and vitamin D metabolism), and
      toxicity biomarkers. Tissue chip experiments were conducted in parallel with
      traditional 2D culture conditions using two different renal proximal tubule
      epithelial cell sources. The results of these studies were then compared to the
      findings reported by the tissue chip developers. While the overall
      transferability of this advanced tissue chip platform was a success, the
      reproducibility with the original report was greatly dependent on the cell
      source. This study demonstrates critical importance of developing
      microphysiological platforms using renewable cell sources.

PMID- 30291269
TI  - Real-time Brain Tumor imaging with endogenous fluorophores: a diagnosis proof-of
      concept study on fresh human samples.
AB  - The primary line of therapy for high-grade brain tumor is surgical resection,
      however, identifying tumor margins in vivo remains a major challenge. Despite the
      progress in computer-assisted imaging techniques, biopsy analysis remains the
      standard diagnostic tool when it comes to delineating tumor margins. Our group
      aims to answer this challenge by exploiting optical imaging of endogenous
      fluorescence in order to provide a reliable and reproducible diagnosis close to
      neuropathology. In this study, we first establish the ability of two-photon
      microscopy (TPM) to discriminate normal brain tissue from glioblastomas and brain
      metastasis using the endogenous fluorescence response of fresh human brain
      sample. Two-photon fluorescence images were compared to gold standard
      neuropathology. "Blind" diagnosis realized by a neuropathologist on a group of
      TPM images show a good sensitivity, 100%, and specificity, 50% to discriminate
      non tumoral brain tissue versus glioblastoma or brain metastasis. Quantitative
      analysis on spectral and fluorescence lifetime measurements resulted in building
      a scoring system to discriminate brain tissue samples.

PMID- 30291270
TI  - Chemical transfer of dissolved organic matter from surface seawater to sea spray
      water-soluble organic aerosol in the marine atmosphere.
AB  - It is critical to understand how variations in chemical composition in surface
      seawater (SSW) affect the chemistry of marine atmospheric aerosols. We
      investigated the sea-to-air transfer of dissolved organic carbon (DOC) via cruise
      measurements of both ambient aerosols and SSW in the Oyashio and its coastal
      regions, the western subarctic Pacific during early spring. Sea spray aerosols
      (SSAs) were selected based on the stable carbon isotope ratio of water-soluble
      organic carbon (WSOC) (delta13CWSOC) and concentrations of glucose as a molecular
      tracer in marine aerosols together with local surface wind speed data. For both
      SSA and SSW samples, excitation-emission matrices were obtained to examine the
      transfer of fluorescent organic material. We found that the ratios of
      fluorescence intensity of humic-like and protein-like substances in the
      submicrometer SSAs were significantly larger than those in the bulk SSW (~63%).
      This ratio was also larger for the supermicrometer SSAs than for the SSW. The
      results suggest significant decomposition of protein-like DOC on a timescale of
      <12-24 h and/or preferential production of humic-like substances in the
      atmospheric aerosols regardless of the particle size. This study provides unique
      insights into the complex transfer of DOC from the ocean surface to the
      atmosphere.

PMID- 30291271
TI  - Dual Porosity Protein-based Scaffolds with Enhanced Cell Infiltration and
      Proliferation.
AB  - 3D dual porosity protein-based scaffolds have been developed using the
      combination of foaming and freeze-drying. The suggested approach leads to the
      production of large, highly porous scaffolds with negligible shrinkage and
      deformation compared to the conventional freeze-drying method. Scanning electron
      microscopy, standard histological processing and mercury intrusion porosimetry
      confirmed the formation of a dual network in the form of big primary pores (243
      +/- 14 um) embracing smaller secondary pores (42 +/- 3 um) opened onto their
      surface, resembling a vascular network. High interconnectivity of the pores,
      confirmed by micro-CT, is shown to improve diffusion kinetics and support a
      relatively uniform distribution of isolated human dental pulp stem cells within
      the scaffold compared to conventional scaffolds. Dual network scaffolds indicate
      more than three times as high cell proliferation capability as conventional
      scaffolds in 14 days.

PMID- 30291272
TI  - Structural insights into pro-aggregation effects of C. elegans CRAM-1 and its
      human ortholog SERF2.
AB  - Toxic protein aggregates are key features of progressive neurodegenerative
      diseases. In addition to "seed" proteins diagnostic for each neuropathy (e.g.,
      Abeta1-42 and tau in Alzheimer's disease), aggregates contain numerous other
      proteins, many of which are common to aggregates from diverse diseases. We
      reported that CRAM-1, discovered in insoluble aggregates of C. elegans expressing
      Q40::YFP, blocks proteasomal degradation of ubiquitinated proteins and thus
      promotes aggregation. We now show that CRAM-1 contains three alpha-helical
      segments forming a UBA-like domain, structurally similar to those of mammalian
      adaptor proteins (e.g. RAD23, SQSTM1/p62) that shuttle ubiquitinated cargos to
      proteasomes or autophagosomes for degradation. Molecular modeling indicates that
      CRAM-1, through this UBA-like domain, can form tight complexes with mono- and di
      ubiquitin and may thus prevent tagged proteins from interacting with
      adaptor/shuttle proteins required for degradation. A human ortholog of CRAM-1,
      SERF2 (also largely disordered), promotes aggregation in SH-SY5Y-APPSw human
      neuroblastoma cells, since SERF2 knockdown protects these cells from amyloid
      formation. Atomistic molecular-dynamic simulations predict spontaneous unfolding
      of SERF2, and computational large-scale protein-protein interactions predict its
      stable binding to ubiquitins. SERF2 is also predicted to bind to most proteins
      screened at random, although with lower average stability than to ubiquitins,
      suggesting roles in aggregation initiation and/or progression.

PMID- 30291273
TI  - Novel multiplex PCR-SSP method for centromeric KIR allele discrimination.
AB  - Allelic diversity of the KIR2DL receptors drive differential expression and
      ligand-binding affinities that impact natural killer cell function and patient
      outcomes for diverse cancers. We have developed a global intermediate resolution
      amplification-refractory mutation system (ARMS) PCR-SSP method for distinguishing
      functionally relevant subgroups of the KIR2DL receptors, as defined by
      phylogenetic study of the protein sequences. Use of the ARMS design makes the
      method reliable and usable as a kit, with all reactions utilizing the same
      conditions. Six reactions define six subgroups of KIR2DL1; four reactions define
      three subgroups of KIR2DL2; and five reactions define four subgroups of KIR2DL3.
      Using KIR allele data from a cohort of 426 European-Americans, we identified the
      most common KIR2DL subtypes and developed the high-throughput PCR-based
      methodology, which was validated on a separate cohort of 260 healthy donors.
      Linkage disequilibrium analysis between the different KIR2DL alleles revealed
      that seven allelic combinations represent more than 95% of the observed
      population genotypes for KIR2DL1/L2/L3. In summary, our findings enable rapid
      typing of the most common KIR2DL receptor subtypes, allowing more accurate
      prediction of co-inheritance and providing a useful tool for the discrimination
      of observed differences in surface expression and effector function among NK
      cells exhibiting disparate KIR2DL allotypes.

PMID- 30291274
TI  - The quantum Zeno and anti-Zeno effects with non-selective projective
      measurements.
AB  - In studies of the quantum Zeno and anti-Zeno effects, it is usual to consider
      rapid projective measurements with equal time intervals being performed on the
      system to check whether or not the system is in the initial state. These
      projective measurements are selective measurements in the sense that the
      measurement results are read out and only the case where all the measurement
      results correspond to the initial state is considered in the analysis of the
      effect of the measurements. In this paper, we extend such a treatment to consider
      the effect of repeated non-selective projective measurements - only the final
      measurement is required to correspond to the initial state, while we do not know
      the results of the intermediate measurements. We present a general formalism to
      derive the effective decay rate of the initial quantum state with such
      nonselective measurements. Importantly, we show that there is a difference
      between using non-selective projective measurements and the usual approach of
      considering only selective measurements only if we go beyond the weak system
      environment coupling regime in models other than the usual population decay
      models. As such, we then apply our formalism to investigate the quantum Zeno and
      anti-Zeno effects for three exactly solvable system-environment models: a single
      two-level system undergoing dephasing, a single two-level system interacting with
      an environment of two-level systems and a large spin undergoing dephasing. Our
      results show that the quantum Zeno and anti-Zeno effects in the presence of non
      selective projective measurements can differ very significantly as compared to
      the repeated selective measurement scenario.

PMID- 30291275
TI  - Fiber-bundle illumination: realizing high-degree time-multiplexed multifocal
      multiphoton microscopy with simplicity.
AB  - High-degree time-multiplexed multifocal multiphoton microscopy was expected to
      provide a facile path to scanningless optical-sectioning and the fast imaging of
      dynamic three-dimensional biological systems. However, physical constraints on
      typical time multiplexing devices, arising from diffraction in the free-space
      propagation of light waves, lead to significant manufacturing difficulties and
      have prevented the experimental realization of high-degree time multiplexing. To
      resolve this issue, we have developed a novel method using optical fiber bundles
      of various lengths to confine the diffraction of propagating light waves and to
      create a time multiplexing effect. Through this method, we experimentally
      demonstrate the highest degree of time multiplexing ever achieved in multifocal
      multiphoton microscopy (~50 times larger than conventional approaches), and hence
      the potential of using simply-manufactured devices for scanningless optical
      sectioning of biological systems.

PMID- 30291276
TI  - Developmental asynchrony and antagonism of sex determination pathways in a lizard
      with temperature-induced sex reversal.
AB  - Vertebrate sex differentiation follows a conserved suite of developmental events:
      the bipotential gonads differentiate and shortly thereafter sex specific traits
      become dimorphic. However, this may not apply to squamates, a diverse vertebrate
      lineage comprising of many species with thermosensitive sexual development. Of
      the three species with data on the relative timing of gonad differentiation and
      genital dimorphism, the females of two (Niveoscincus ocellatus and Barisia
      imbricata) exhibit a phase of temporary pseudohermaphroditism or TPH (gonads have
      differentiated well before genital dimorphism). We report a third example of TPH
      in Pogona vitticeps, an agamid with temperature-induced male to female sex
      reversal. These findings suggest that for female squamates, genital and gonad
      development may not be closely synchronised, so that TPH may be common. We
      further observed a high frequency of ovotestes, a usually rare gonadal phenotype
      characterised by a mix of male and female structures, exclusively associated with
      temperature-induced sex reversal. We propose that ovotestes are evidence of a
      period of antagonism between male and female sex-determining pathways during sex
      reversal. Female sexual development in squamates is considerably more complex
      than has been appreciated, providing numerous avenues for future exploration of
      the genetic and hormonal cues that govern sexual development.

PMID- 30291277
TI  - Mathematical Modeling and Analyses of Interspike-Intervals of Spontaneous
      Activity in Afferent Neurons of the Zebrafish Lateral Line.
AB  - Without stimuli, hair cells spontaneously release neurotransmitter leading to
      spontaneous generation of action potentials (spikes) in innervating afferent
      neurons. We analyzed spontaneous spike patterns recorded from the lateral line of
      zebrafish and found that distributions of interspike intervals (ISIs) either have
      an exponential shape or an "L" shape that is characterized by a sharp decay but
      wide tail. ISI data were fitted to renewal-process models that accounted for the
      neuron refractory periods and hair-cell synaptic release. Modeling the timing of
      synaptic release using a mixture of two exponential distributions yielded the
      best fit for our ISI data. Additionally, lateral line ISIs displayed positive
      serial correlation and appeared to exhibit switching between faster and slower
      modes of spike generation. This pattern contrasts with previous findings from the
      auditory system where ISIs tended to have negative serial correlation due to
      synaptic depletion. We propose that afferent neuron innervation with multiple and
      heterogenous hair-cells synapses, each influenced by changes in calcium domains,
      can serve as a mechanism for the random switching behavior. Overall, our analyses
      provide evidence of how physiological similarities and differences between
      synapses and innervation patterns in the auditory, vestibular, and lateral line
      systems can lead to variations in spontaneous activity.

PMID- 30291278
TI  - Phenology determines the robustness of plant-pollinator networks.
AB  - Plant-pollinator systems are essential for ecosystem functioning, which calls for
      an understanding of the determinants of their robustness to environmental
      threats. Previous studies considering such robustness have focused mostly on
      species' connectivity properties, particularly their degree. We hypothesized that
      species' phenological attributes are at least as important as degree as
      determinants of network robustness. To test this, we combined dynamic modeling,
      computer simulation and analysis of data from 12 plant-pollinator networks with
      detailed information of topology of interactions as well as species' phenology of
      plant flowering and pollinator emergence. We found that phenological attributes
      are strong determinants of network robustness, a result consistent across the
      networks studied. Plant species persistence was most sensitive to increased
      larval mortality of pollinators that start earlier or finish later in the season.
      Pollinator persistence was especially sensitive to decreased visitation rates and
      increased larval mortality of specialists. Our findings suggest that seasonality
      of climatic events and anthropic impacts such as the release of pollutants is
      critical for the future integrity of terrestrial biodiversity.

PMID- 30291279
TI  - CCDC114 is mutated in patient with a complex phenotype combining primary ciliary
      dyskinesia, sensorineural deafness, and renal disease.
AB  - Ciliopathies-are widely recognized and associated with a wide variety of
      developmental and degenerative disorders. Most cilia-related diseases have renal
      manifestation, and there is a cross- overlapping relationship between gene
      mutations and cilia disease. Here, we investigated the clinical and pathological
      manifestation of a rare disease patient. We present the case of a 15-year-old
      child with dysplasia and multiple-organ damage who was initially diagnosed with
      nephrotic syndrome. The patient's kidney disease progressed to renal failure and
      received hemodialysis 10 months after renal biopsy. The individual presented
      primary ciliary dyskinesia (PCD) and additional symptoms including sensorineural
      deafness, kidney dysplasia, severe kidney function loss, and congenital heart
      disease which potentially linked to primary cilia deficiency. Cilia
      immunofluorescence of renal tissue showed a decrease in the number of cilium of
      the patient compared to the normal kidney. We identified a site mutation in
      CCDC114 (NM_144577 exon7 c. 596Ca T p. Ala199Val) by whole-exon sequences. We
      found that CCDC114 located at the basal body at cilia and the knockdown of
      CCDC114 could affect the occurrence of cilia in hRPE1 cells. The previous study
      of CCDC114 mainly lies in the motile cilia, and this study found that its impact
      on primary cilia thus broadened the understanding of overlapping function of
      different types of cilia.

PMID- 30291280
TI  - Evidence of a Causal Role for mid-Ventrolateral Prefrontal Cortex Based
      Functional Networks in Retrieving High-Fidelity Memory.
AB  - Functional neuroimaging studies have implicated regions of both ventrolateral
      prefrontal cortex (VLPFC) and angular gyrus in processes associated with
      retrieving goal-relevant information, which increases the fidelity and richness
      of long-term memory (LTM). To further investigate the roles of these cortical
      regions as nodes in functional networks with memory regions of the medial
      temporal lobe (MTL), we used fMRI-guided, 1 Hz repetitive transcranial magnetic
      stimulation (rTMS) to perturb normal neuronal function. The aim was to test the
      causal roles of left mid-VLPFC and left angular gyrus (AG) in MTL-VLPFC-parietal
      networks that have been associated with high-fidelity memory retrieval. rTMS
      treatments were administered immediately before blocks in an old/new recognition
      test, which was based on a mnemonic similarity task requiring discrimination of
      previously studied pictures of common objects. Capability for mnemonic
      discrimination was evaluated after each of three conditions: placebo control
      (rTMS at somatosensory cortex), mid-VLPFC target (rTMS at left pars triangularis)
      and parietal target (rTMS at left AG). The results showed the effect of rTMS
      perturbation of mid-VLPFC diminished subsequent discrimination-based memory
      performance, relative to placebo control, and no significant effect of
      perturbation of AG. These findings show a causal role for functional networks
      with left mid-VLPFC in high-fidelity retrieval.

PMID- 30291281
TI  - Relationship between Ocular Deviation and Visual Function in Retinitis
      Pigmentosa.
AB  - In retinitis pigmentosa (RP), peripheral visual-field loss starts in early
      stages, whereas central vision loss occurs in advanced stages. Sensory strabismus
      gradually occurs in RP. We investigated the relationship between ocular deviation
      and visual function and explored for sensory strabismus risk factors in 119
      consecutive patients with RP at various stages. We assessed ocular deviation at
      far and near distances, that is the central visual field, using the mean
      deviation (MD) value and visual acuity (VA), and the residual binocular field
      area, using Goldmann perimetry (GP), in 33 patients. The horizontal ocular
      deviation at near distance was >10 degrees  in 30% patients and correlated with
      residual visual function. Although there was no effective cut-off value for
      central visual function, a cut-off residual GP area of 40 cm2 distinguished
      patients with a larger from those with a smaller horizontal ocular deviation at
      far distance (P = 0.04). Our findings suggest that visual function is negatively
      associated with ocular deviation in patients with RP and that the sensory
      strabismus risk is relatively high for patients with a binocular visual field <40
      cm2. Thus, screening for ocular alignment may be necessary for patients with RP
      associated severe vision loss as part of their comprehensive care.

PMID- 30291282
TI  - Genome-wide methylation analysis identifies ELOVL5 as an epigenetic biomarker for
      the risk of type 2 diabetes mellitus.
AB  - Genome-wide DNA methylation has been implicated in complex human diseases. Here,
      we identified epigenetic biomarkers for type 2 diabetes (T2D) underlying
      obesogenic environments. In a blood-based DNA methylation analysis of 11
      monozygotic twins (MZTW) discordant for T2D, we discovered genetically
      independent candidate methylation sites. In a follow-up replication study (17
      MZTW pairs) for external validation, we replicated the T2D-association at a novel
      CpG signal in the ELOVL fatty acid elongase 5 (ELOVL5) gene specific to T2D
      discordant MZTW. For concordant DNA methylation signatures in tissues, we further
      confirmed that a CpG site (cg18681426) was associated with adipogenic
      differentiation between human preadipocytes and adipocytes isolated from the same
      biopsy sample. In addition, the ELOVL5 gene was significantly differentially
      expressed in adipose tissues from unrelated T2D patients and in human pancreatic
      islets. Our results demonstrate that blood-derived DNA methylation is associated
      with T2D risk as a proxy for cumulative epigenetic status in human adipose and
      pancreatic tissues. Moreover, ELOVL5 expression was increased in cellular and
      mouse models of induced obesity-related diabetes. These findings may provide new
      insights into epigenetic architecture by uncovering methylation-based biomarkers.

PMID- 30291283
TI  - Formation of massive iron deposits linked to explosive volcanic eruptions.
AB  - The genetic link between magmas and ore deposit formation is well documented by
      studies of fossil hydrothermal systems associated with magmatic intrusions at
      depth. However, the role of explosive volcanic processes as active agents of
      mineralization remains unexplored owing to the fact that metals and volatiles are
      released into the atmosphere during the eruption of arc volcanoes. Here, we draw
      on observations of the uniquely preserved El Laco iron deposit in the Central
      Andes to shed new light on the metallogenic role of explosive volcanism that
      operates on a global scale. The massive magnetite (Fe3O4) ore bodies at El Laco
      have surface structures remarkably similar to basaltic lava flows, stimulating
      controversy about their origin. A long-standing debate has endured because all
      proposed models were constructed based exclusively on samples collected from
      surface outcrops representing the uppermost and most altered portion of the
      deposit. We overcome this sampling bias by studying samples retrieved from
      several drill cores and surface outcrops. Our results reveal complex
      lithological, textural and geochemical variations characterized by magmatic-like
      features and, most notably, a systematic increase in titanium concentration of
      magnetite with depth that account for an evolving system transitioning from
      purely magmatic to magmatic-hydrothermal conditions. We conclude that El Laco,
      and similar deposits worldwide, formed by a synergistic combination of common
      magmatic processes enhanced during the evolution of caldera-related explosive
      volcanic systems.

PMID- 30291284
TI  - The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial
      Energetics in White Adipose Tissue.
AB  - Obesity and related metabolic pathologies represent a significant public health
      concern. Obesity is associated with increased oxidative stress that damages
      genomic and mitochondrial DNA. Oxidatively-induced lesions in both DNA pools are
      repaired via the base-excision repair pathway, initiated by DNA glycosylases such
      as 8-oxoguanine DNA glycosylase (OGG1). Global deletion of OGG1 and common OGG1
      polymorphisms render mice and humans susceptible to metabolic disease. However,
      the relative contribution of mitochondrial OGG1 to this metabolic phenotype is
      unknown. Here, we demonstrate that transgenic targeting of OGG1 to mitochondria
      confers significant protection from diet-induced obesity, insulin resistance, and
      adipose tissue inflammation. These favorable metabolic phenotypes are mediated by
      an increase in whole body energy expenditure driven by specific metabolic
      adaptations, including increased mitochondrial respiration in white adipose
      tissue of OGG1 transgenic (Ogg1Tg) animals. These data demonstrate a critical
      role for a DNA repair protein in modulating mitochondrial energetics and whole
      body energy balance.

PMID- 30291285
TI  - Contribution of SPI-1 bistability to Salmonella enterica cooperative virulence:
      insights from single cell analysis.
AB  - Salmonella enterica pathogenicity island 1 (SPI-1) is a gene cluster that encodes
      a type III secretion system and effectors involved in epithelial cell invasion.
      SPI-1 undergoes bistable expression, with concomitant formation of SPI-1ON and
      SPI-1OFF lineages. This study describes single cell analysis of SP1-1 bistability
      and epithelial cell invasion, and reports the unsuspected observation that
      optimal invasion of epithelial cells requires the presence of both SPI-1ON and
      SPI-1OFF subpopulations. The contribution of SPI-1OFF cells to optimal invasion
      may rely on their ability to invade epithelial cells if a SPI-1ON subpopulation
      is present. In fact, Salmonella SPI-1 mutants are also able to invade epithelial
      cells in the presence of SPI-1ON Salmonellae, a phenomenon described in the
      1990's by Galan and co-workers. Invasion by SPI-1OFF cells does not seem to
      involve a diffusible factor. A small number of SPI-1ON cells is sufficient to
      endow the bacterial population with invasion capacity, a feature that may permit
      host colonization regardless of the bottlenecks encountered by Salmonella
      populations inside animals.

PMID- 30291286
TI  - Alteration of Serum Free Fatty Acids are Indicators for Progression of Pre
      leukaemia Diseases to Leukaemia.
AB  - Acute Leukaemia (AL) is a neoplasm of WBCs (white blood cells). Being an
      important class of metabolites, alteration in free fatty acids (FFAs) levels play
      a key role in cancer development and progression. As they involve in cell
      signaling, maintain membrane integrity, regulate homeostasis and effect cell and
      tissue functions. Considering this fact, a comprehensive analysis of FFAs was
      conducted to monitor their alteration in AL, pre-leukaemic diseases and healthy
      control. Fifteen FFAs were analyzed in 179 serum samples of myelodysplastic
      syndrome (MDS), aplastic anemia (APA), acute lymphoblastic leukaemia (ALL), acute
      myeloid leukaemia (AML) and healthy control using gas chromatography-multiple
      reaction monitoring-mass spectrometry (GC-MRM-MS). A multivariate statistical
      method of random forest (RF) was employed for chemometric analysis. Serum level
      of two FFAs including C18:0 and C14:0 were found discriminative among all five
      groups, and between ALL and AML, respectively. Moreover, C14:0 was identified as
      differentiated FFAs for systematic progression of pre-leukaemic conditions
      towards AML. C16:0 came as discriminated FFAs between APA and MDS/AML. Over all
      it was identified that FFAs profile not only become altered in leukaemia but also
      in pre-leukaemic diseases.

PMID- 30291287
TI  - Enhancement of PCR Sensitivity and Yield Using Thiol-modified Primers.
AB  - Various additives can enhance the quality of PCR amplification, but these
      generally require considerable optimization to achieve peak performance. Here, we
      demonstrate that the use of thiol-modified primers can enhance both PCR
      sensitivity and yield. In experiments with V. parahaemolyticus genomic DNA, this
      primer modification enhances PCR sensitivity by more than 100-fold, with
      accompanying improvements in amplicon yield. Then, an artificial plasmid with the
      same primer binding regions and different internal amplification sequence was
      designed. The result showed that the amplification also be improved by using the
      same thiol-modified primers. It indicated the enhancement was not caused by the
      effect of the thiol-modified primers on the second structure of amplification
      sequence. Subsequent experiments demonstrate that the effects of this
      modification are potentially due to altered interaction between the primers and
      proteins in the reaction mixture. Amplification with thiol-modified primers was
      strongly inhibited by the presence of extraneous proteins relative to standard
      DNA primers, which indicates that thiol-modified primers may be inhibited due to
      interaction with these proteins. In contaminant-free reactions, however, the
      thiol-modified primers might interact more strongly with DNA polymerase, which
      could in turn improve PCR amplification.

PMID- 30291288
TI  - Energy barriers at grain boundaries dominate charge carrier transport in an
      electron-conductive organic semiconductor.
AB  - Semiconducting organic films that are at the heart of light-emitting diodes,
      solar cells and transistors frequently contain a large number of morphological
      defects, most prominently at the interconnects between crystalline regions. These
      grain boundaries can dominate the overall (opto-)electronic properties of the
      entire device and their exact morphological and energetic nature is still under
      current debate. Here, we explore in detail the energetics at the grain boundaries
      of a novel electron conductive perylene diimide thin film. Via a combination of
      temperature dependent charge transport measurements and ab-initio simulations at
      atomistic resolution, we identify that energetic barriers at grain boundaries
      dominate charge transport in our system. This novel aspect of physics at the
      grain boundary is distinct from previously identified grain-boundary defects that
      had been explained by trapping of charges. We furthermore derive molecular design
      criteria to suppress such energetic barriers at grain boundaries in future, more
      efficient organic semiconductors.

PMID- 30291290
TI  - Analysis of coupling between magnetic dipoles enhanced by metasurfaces for
      wireless power transfer efficiency improvement.
AB  - In this paper, we investigate the possibility of improving efficiency in non
      radiative wireless power transfer (WPT) using metasurfaces embedded between two
      current varying coils and present a complete theoretical analysis of this system.
      We use a point-dipole approximation to calculate the fields of the coils. Based
      on this method, we obtain closed-form and analytical expressions which would
      provide basic insights into the possibility of efficiency improvement with
      metasurface. In our analysis, we use the equivalent two sided surface impedance
      model to analyze the metasurface and to show for which equivalent surface
      impedance the WPT efficiency will be maximized at the design frequency. Then, to
      validate our theory, we perform a full-wave simulation for analyzing a practical
      WPT system, including two circular loop antennas at 13.56 MHz. We then design a
      metasurface composed of single-sided CLSRRs to achieve a magnetic lensing based
      on the calculated equivalent surface impedance. The analytical results and full
      wave simulations indicated non-radiative WPT efficiency improvement due to
      amplifying the near evanescent field which can be achieved through inserting the
      proposed metasurface.

PMID- 30291289
TI  - Recommendations for improving accuracy of gene expression data in bone and
      cartilage tissue engineering.
AB  - Autogenous tissue grafting remains the gold standard in the treatment of critical
      sized bone and certain cartilage defects, while the translation of tissue
      engineered osteogenesis or chondrogenesis from the lab bench into clinical
      practice, utilizing natural or synthetic biomimetic devices, remains challenging.
      One of the crucial underestimated reasons for non-translatability could be the
      imprecision and inconsistency of generated gene expression profiles, utilizing
      improperly optimized and standardized quantitative gene assays. Utilizing GeNorm
      for downstream qRT-PCR applications, the stability of reference genes in relation
      to optimal cDNA amounts was assessed on human bone marrow-derived mesenchymal and
      adipose-derived stem cells neat and made to differentiate into chondrocytes
      including normal human derived chondrocytes and muscle tissue from rats. Results
      showed that reference genes can vary substantially across separately and/or
      combined cell lines and/or tissue types including treatment parameters. The
      recommendations to all bone and cartilage tissue engineers utilizing qRT-PCR is
      not to assume that reference gene stability and quantity remain conserved across
      cell lines or tissue types but to always determine, for each new experiment, the
      stability and normalization quantity of reference genes anew.

PMID- 30291291
TI  - First assessment of the comparative toxicity of ivermectin and moxidectin in
      adult dung beetles: Sub-lethal symptoms and pre-lethal consequences.
AB  - Among macrocyclic lactones (ML), ivermectin (IVM) and moxidectin (MOX)
      potentially affect all Ecdysozoan species, with dung beetles being particularly
      sensitive. The comparative effects of IVM and MOX on adult dung beetles were
      assessed for the first time to determine both the physiological sub-lethal
      symptoms and pre-lethal consequences. Inhibition of antennal response and ataxia
      were tested as two intuitive and ecologically relevant parameters by obtaining
      the lowest observed effect concentration (LOEC) values and interpolating other
      relevant toxicity thresholds derived from concentration-response curves (IC50, as
      the concentration of each ML where the antennal response is inhibited by half;
      and pLC50, as the quantity of ingested ML where partial paralysis was observed by
      half of treated individuals) from concentration-response curves. Both sub-lethal
      and pre-lethal symptoms obtained in this study coincided in that IVM was six
      times more toxic than MOX for adult dung beetles. Values of LOEC, IC50 and pLC50
      obtained for IVM and MOX evaluated in an environmental context indicate that MOX,
      despite needing more time for tis elimination in the faeces, would be twice as
      harmful to dung beetles as IVM. This approach will be valuable to clarify the
      real impact of MLs on dung beetle health and to avoid the subsequent
      environmental consequences.

PMID- 30291292
TI  - A balancing act: dual immune-checkpoint inhibition for oesophagogastric cancer.

PMID- 30291293
TI  - Ankyrin Repeat Domain 1 Overexpression is Associated with Common Resistance to
      Afatinib and Osimertinib in EGFR-mutant Lung Cancer.
AB  - Overcoming acquired resistance to epidermal growth factor receptor tyrosine
      kinase inhibitors (EGFR-TKIs) is critical in combating EGFR-mutant non-small cell
      lung cancer (NSCLC). We tried to construct a novel therapeutic strategy to
      conquer the resistance to second-and third-generation EGFR-TKIs in EGFR-positive
      NSCLC patients. We established afatinib- and osimertinib-resistant lung
      adenocarcinoma cell lines. Exome sequencing, cDNA array and miRNA microarray were
      performed using the established cell lines to discover novel therapeutic targets
      associated with the resistance to second-and third-generation EGFR-TKIs. We found
      that ANKRD1 which is associated with the epithelial-mesenchymal transition (EMT)
      phenomenon and anti-apoptosis, was overexpressed in the second-and third
      generation EGFR-TKIs-resistant cells at the mRNA and protein expression levels.
      When ANKRD1 was silenced in the EGFR-TKIs-resistant cell lines, afatinib and
      osimertinib could induce apoptosis of the cell lines. Imatinib could inhibit
      ANKRD1 expression, resulting in restoration of the sensitivity to afatinib and
      osimertinib of EGFR-TKI-resistant cells. In EGFR-mutant NSCLC patients, ANKRD1
      was overexpressed in the tumor after the failure of EGFR-TKI therapy, especially
      after long-duration EGFR-TKI treatments. ANKRD1 overexpression which was
      associated with EMT features and anti-apoptosis, was commonly involved in
      resistance to second-and third-generation EGFR-TKIs. ANKRD1 inhibition could be a
      promising therapeutic strategy in EGFR-mutant NSCLC patients.

PMID- 30291294
TI  - Variability of crossing phase in older people with Parkinson's disease is
      dependent of obstacle height.
AB  - Our aim was investigating variability in spatiotemporal parameters and kinetics
      of obstacle avoidance steps of different height obstacles in people with
      Parkinson's disease (PD) and healthy older people. Twenty-eight participants have
      included (15 PD - stage disease: 2.1 +/- 0.4 pts) and 13 healthy older people
      (control group). Each subject performed 10 trials of the following tasks: low
      obstacle, intermediate obstacle and high obstacle. The presentation order was
      randomized by block for each condition and participant. The spatiotemporal
      parameters was collected by GAITRite. An optoelectronic system (Optotrak Northern
      Digital Inc.) with 100 Hz of frequency was used to collect obstacle parameters.
      The kinect parameters (propulsion impulse and braking impulse) were acquire
      through two force plates (AccuGait), with a frequency of acquisition 200 Hz.
      Intersteps variability was calculated throughout mean values, standard deviation
      and coefficient of variation of two obstacle avoidance steps for each trial. PD
      group presented greater variability than control group on vertical and horizontal
      distances to the obstacle. Obstacle height did not change kinect's parameters for
      both groups. The combination of task complexity (obstacle height) and disease
      impairments (gait alteration, loss of balance, etc) contributing for greater
      variability of Parkinson's group. Besides, low obstacle and high obstacle seem to
      exacerbate variability of distance between obstacle and foot.

PMID- 30291295
TI  - Empagliflozin Ammeliorates High Glucose Induced-Cardiac Dysfuntion in Human iPSC
      Derived Cardiomyocytes.
AB  - Empagliflozin, a sodium-glucose co-transporter (SGLT) inhibitor, reduces heart
      failure and sudden cardiac death but the underlying mechanisms remain elusive. In
      cardiomyocytes, SGLT1 and SGLT2 expression is upregulated in diabetes mellitus,
      heart failure, and myocardial infarction. We hypothesise that empagliflozin
      exerts direct effects on cardiomyocytes that attenuate diabetic cardiomyopathy.
      To test this hypothesis, cardiomyocytes derived from human induced pluripotent
      stem cells (hiPSCs) were used to test the potential effects of empagliflozin on
      neutralization of cardiac dysfunction induced by diabetic-like cultures. Our
      results indicated that insulin-free high glucose culture significantly increased
      the size of and NPPB, SGLT1 and SGLT2 expression of hiPSC-derived cardiomyocytes.
      In addition, high glucose-treated hiPSC-derived cardiomyocytes exhibited reduced
      contractility regardless of the increased calcium transient capacity.
      Interestingly, application of empagliflozin before or after high glucose
      treatment effectively reduced the high glucose-induced cardiac abnormalities.
      Since application of empagliflozin did not significantly alter viability or
      glycolytic capacity of the hiPSC-derived cardiomyocytes, it is plausible that
      empagliflozin exerts its effects via the down-regulation of SGLT1, SGLT2 and
      GLUT1 expression. These observations provide supportive evidence that may help
      explain its unexpected benefit observed in the EMPA-REG trial.

PMID- 30291296
TI  - Splenectomy modulates early immuno-inflammatory responses to trauma-hemorrhage
      and protects mice against secondary sepsis.
AB  - In polytrauma patients, the impact of splenectomy is equivocal, ranging from
      negative to protective. We investigated the impact of splenectomy on immune
      responses in the 1st-hit polytrauma alone and on survival in the post-traumatic
      sepsis (2nd hit). Female BALB/c mice underwent polytrauma (1st hit) consisting of
      either a) TH: femur fracture, hemorrhagic shock or b) TSH: splenectomy, femur
      fracture, hemorrhagic shock. Additionally, the polytrauma hit was followed by
      cecal ligation and puncture (CLP) 48 h later and compared to CLP alone.
      Splenectomy improved the 28-day survival in secondary sepsis to 92% (from 62%),
      while TH lowered it to 46% (p < 0.05). The improved survival was concurrent with
      lower release of inflammatory cytokines (IL-6, CXCL-1, MCP-1) and increase of C5a
      post-CLP. In the polytrauma hit alone, TSH induced stronger neutrophilia (1.9
      fold) and lymphocytosis (1.7 fold) when compared to TH mice. Moreover, TSH
      resulted in a 41% rise of regulatory T-cells and reduced the median fluorescence
      intensity of MHC-2 on monocytes by 55% within 48 h (p < 0.05). Conversely,
      leukocyte phagocytic capacity was significantly increased by 4-fold after TSH
      despite a similar M1/M2 macrophage profile in both groups. Summarizing,
      splenectomy provoked both immuno-suppressive and immuno-stimulatory responses but
      was life-saving in secondary sepsis. Additionally, the polytrauma components in 2
      hit models should be tested for their effects on outcome; the presumed end-effect
      of the 1st hit solely based on the common immuno-inflammatory parameters could be
      misleading.

PMID- 30291297
TI  - A new pharmacokinetic model for 90Y-ibritumomab tiuxetan based on 3-dimensional
      dosimetry.
AB  - Monoclonal antibodies (mAbs) are key components in several therapies for cancer
      and inflammatory diseases but current knowledge of their clinical
      pharmacokinetics and distribution in human tissues remains incomplete.
      Consequently, optimal dosing and scheduling in clinics are affected. With
      sequential radiolabeled mAb-based imaging, radiation dosing in tissues/organs can
      be calculated to provide a better assessment of mAb concentrations in tissues.
      This is the first pharmacokinetic model of 90Y-Ibritumomab tiuxetan (90Y-IT) in
      humans to be described, based on three-dimensional (3D) dosimetry using single
      photon emission computed-tomography coupled with computed-tomography. 19 patients
      with follicular lymphoma were treated initially with 90Y-IT in the FIZZ trial.
      Based on a compartmental approach individualising the vascular compartment within
      studied organs, this study proposes a reliable pharmacokinetic (PK) five
      compartment model replacing the currently used two-compartment model and
      constitutes a new direction for further research. This model provides exchange
      constants between the different tissues, Area Under the Curve of 111In-IT in
      blood (AUC) and Mean Residence Time (MRT) that have not been reported so far for
      IT. Finally, the elimination process appears to occur in a compartment other than
      the liver or the spleen and suggests the metabolism of mAbs may take place mainly
      on the vascular compartment level.

PMID- 30291298
TI  - Spatial congruence between multiple stressors in the Mediterranean Sea may reduce
      its resilience to climate impacts.
AB  - Climate impacts on marine ecosystems may be exacerbated by other, more local
      stressors interacting synergistically, such as pollution and overexploitation of
      marine resources. The reduction of these human stressors has been proposed as an
      achievable way of retaining ecosystems within a "safe operating space" (SOS),
      where they remain resilient to ongoing climate change. However, the operability
      of an SOS requires a thorough understanding of the spatial distribution of these
      climate and human impacts. Using the Mediterranean Sea as a case study, we
      illustrate the spatial congruence between climate and human stressors impacting
      this iconic "miniature ocean" synergistically. We use long-term, spatially
      explicit information on the distribution of multiple stressors to identify those
      highly impacted marine areas where human stressors should be prioritized for
      management if the resilience to climate impacts is to be maintained. Based on our
      spatial analysis, we exemplify how the management of an essential supporting
      service (seafood provision) and the conservation of a highly impacted
      Mediterranean sub-region (the Adriatic Sea) may benefit from the SOS framework.

PMID- 30291299
TI  - Author Correction: The emerging field of epigenetics in neurodegeneration and
      neuroprotection.
AB  - In Box 1 of this article, the positioning of the amino acid residues on the tail
      of histone H3 in part b of the figure was incorrect. These should have been
      oriented so that the K4 residue was the most distal labelled residue from the
      nucleosome core region. The corrected figure is shown below. The authors and
      editors thank T. Brown, R. Lober and C. Waker for bringing this error to our
      attention.

PMID- 30291300
TI  - Rewarding gut feeling.

PMID- 30291301
TI  - In or out of synch.

PMID- 30291302
TI  - Number crunching.

PMID- 30291304
TI  - Profilin(g) Asgard archaea.

PMID- 30291303
TI  - Bulk band inversion and surface Dirac cones in LaSb and LaBi: Prediction of a new
      topological heterostructure.
AB  - We perform ab initio investigations of the bulk and surface band structures of
      LaSb and LaBi and resolve the existing disagreements about the topological
      property of LaSb, considering LaBi as a reference. We examine the bulk band
      structure for band inversion, along with the stability of surface Dirac cones (if
      any) to time-reversal-preserving perturbations, as a strong diagnostic test for
      determining the topological character of LaSb, LaBi and LaSb-LaBi multilayer. A
      detailed ab initio investigation of a multilayer consisting of alternating unit
      cells of LaSb and LaBi shows the presence of band inversion in the bulk and a
      massless Dirac cone on the (001) surface, which remains stable under the
      influence of time-reversal-preserving perturbations, thus confirming the
      topologically non-trivial nature of the multilayer in which the electronic
      properties can be tailored as per requirement. A detailed [Formula: see text]
      invariant calculation is performed to arrive at a holistic conclusion.

PMID- 30291305
TI  - Diet and the mammary gland microbiome.

PMID- 30291306
TI  - Not so crystal clear: observations from a case of crystalline arthritis with
      cytokine release syndrome (CRS) after chimeric antigen receptor (CAR)-T cell
      therapy.

PMID- 30291308
TI  - Gene editing reveals the effect of thousands of variants in a key cancer gene.

PMID- 30291307
TI  - Gut dysbiosis is associated with the reduced exercise capacity of elderly
      patients with hypertension.
AB  - Hypertension is a global health issue, and a reduced exercise capacity is
      unavoidable for older people. According to recent clinical studies, the
      intestinal microbiota play a crucial role in the pathogenesis of many human
      diseases. We investigated whether specific alterations in the gut microbiota
      contribute to the reduced exercise capacity of elderly patients with
      hypertension. This study enrolled 56 subjects, and all patients performed a
      cardiopulmonary exercise test and underwent fecal bacteria sequencing (16 s
      ribosomal RNA V4 region). According to peak oxygen uptake values, patients were
      divided into three groups (Weber A = 19, Weber B = 20, and Weber C = 17). The
      alpha diversity was not significantly different among the three groups. Regarding
      the beta diversity, Weber A samples were separate from the other two groups in
      the nonmetric multidimensional scaling ordination plot (ANOSIM pairwise
      comparisons generated an R > 0.5; p < 0.05). The abundance of Betaproteobacteria,
      Burkholderiales, Alcaligenaceae, Faecalibacterium and Ruminococcaceae was
      diminished in subjects with a reduced exercise capacity (LDA score > 4.0).
      Escherichia coli are a primary producer of trimethylamine and inflammation in the
      human gut, and the abundance of this bacteria was increased in patients with a
      reduced exercise capacity (LDA score > 4.0). On the other hand, Lachnospiraceae
      Eubacterium_hallii_group, Lachnospiraceae-Lachnoclostridium, Lachnospiraceae
      Blautia-Ruminococcus_sp__5_1_39BFAA, and Ruminococcaceae-Faecalibacterium belong
      to the order Clostridiales that are likely to produce short-chain fatty acids
      (LDA score > 4.0), and some of these species were enriched in the Weber B or
      Weber C group in multiple comparisons. Our data pointed to an altered gut
      microbiota as a potential contributor to the pathogenesis and progression of the
      reduced exercise capacity of elderly patients with hypertension.

PMID- 30291309
TI  - A dual origin for blood vessels.

PMID- 30291310
TI  - Foraging skills develop over generations in the wild.

PMID- 30291312
TI  - Replication and novel analysis of age and sex effects on the neurologic and
      functional value of each spinal segment in the US healthcare setting.
AB  - STUDY DESIGN: Replication of previously developed prognostic model. OBJECTIVES:
      In motor complete injuries at admission to rehabilitation, perform; (1)
      replication analyses of the relationships between ISNCSCI motor level and motor
      scores and SCIM and (2) novel analyses to determine if age and/or sex moderate
      relationship between neurological impairment and function. SETTING: Admission to
      initial inpatient rehabilitation in the United States. METHODS: Post-Hoc analyses
      of data collected as part of a separate study. Replication analyses: (1)
      Pearson's correlation assessed relationship strength between neurologic
      impairment and function. (2) Multiple linear regression assessed if center or age
      influenced functional outcome. Novel analyses: (1) Moderated multiple regression
      assessed if age and/or sex moderated the lesion level-function relationship.
      RESULTS: Of the 406 datasets, 161 were motor complete injuries, and included in
      the analyses. Median time post injury at admission to rehabilitation was 19 days.
      Our replication analyses confirmed the neurologic and functional value of each
      spinal segment reported by the EM-SCI group (all p <= 0.018). We failed to
      confirm their reported age effect (p = 0.05) and non-effect of center (p =
      0.037). Our novel analyses indicated that age coded as above/below 50 moderated
      the relationship between neurologic impairment and function (p = 0.038) in
      cervical injuries only, but that age coded as above/below 35 (all p >= 0.510) and
      sex (all p >= 0.465) did not. CONCLUSIONS: The neurological and functional value
      of each segment is consistent across very different healthcare settings in early
      and late sub-acute stages and minimally impacted by age and sex. Differences
      related to centers and age may confound efficacy trials. SPONSORSHIP: The Miami
      Project to Cure Paralysis; The Craig H. Neilsen Foundation (83492).

PMID- 30291311
TI  - Temporal differentiation of bovine airway epithelial cells grown at an air-liquid
      interface.
AB  - There is an urgent need to develop improved, physiologically-relevant in vitro
      models of airway epithelia with which to better understand the pathological
      processes associated with infection, allergies and toxicological insults of the
      respiratory tract of both humans and domesticated animals. In the present study,
      we have characterised the proliferation and differentiation of primary bovine
      bronchial epithelial cells (BBECs) grown at an air-liquid interface (ALI) at
      three-day intervals over a period of 42 days from the introduction of the ALI.
      The differentiated BBEC model was highly representative of the ex vivo epithelium
      from which the epithelial cells were derived; a columnar, pseudostratified
      epithelium that was highly reflective of native airway epithelium was formed
      which comprised ciliated, goblet and basal cells. The hallmark defences of the
      respiratory tract, namely barrier function and mucociliary clearance, were
      present, thus demonstrating that the model is an excellent mimic of bovine
      respiratory epithelium. The epithelium was fully differentiated by day 21 post
      ALI and, crucially, remained healthy and stable for a further 21 days. Thus, the
      differentiated BBEC model has a three-week window which will allow wide-ranging
      and long-term experiments to be performed in the fields of infection, toxicology
      or general airway physiology.

PMID- 30291313
TI  - Cavernosal hydrogen sulfide levels are associated with nitric oxide and
      hemeoxygenase levels in diabetic rats.
AB  - Penile erection is a neuromuscular event modulated by psyche, hormones as well as
      neurotransmitters. This pre-clinical study aimed to assess hydrogen sulfide (H2S)
      relationship with nitric oxide (NO) and hemeoxygenase (HO) in the cavernous
      tissues of diabetic rats. Overall, 90 adult male rats were investigated (6
      groups, n = 15 each). They were subdivided into the following groups; untreated
      rats, rats treated with H2S donor/inhibitor, induced diabetic rats, diabetic rats
      treated with H2S donor/inhibitor. At the 6th week, the rats were killed to assess
      cavernous tissue cGMP, NO, H2S, HO enzyme activity levels. The rats treated with
      H2S donor showed increased mean cavernous tissue cGMP, NO, H2S, and HO enzyme
      activity levels whereas induced diabetic rats and rats treated with H2S inhibitor
      showed significant decreases in these parameters compared with the untreated
      rats. On the other hands, diabetic rats treated with H2S donor showed elevated
      mean cavernous tissue cGMP, NO, H2S, and HO enzyme activity levels whereas
      diabetic rats treated with H2S inhibitor showed significant decreases in these
      parameters compared with diabetic rats. Cavernous tissue H2S levels exhibited
      significant positive correlations with the cavernous tissue levels cGMP, NO, and
      HO enzyme activity levels. From these results, it could be concluded that
      cavernous tissues H2S plays a role of male sexual health by affecting cavernous
      tissues NO and HO enzyme activity in general and in diabetics in particular.

PMID- 30291314
TI  - An important step on the long path to clinical application of in utero gene
      therapy.

PMID- 30291315
TI  - Publisher Correction: Anisotropic polarization-induced conductance at a
      ferroelectric-insulator interface.
AB  - In the version of this Letter originally published, the right-hand arrow in Fig.
      3b was incorrectly labelled; see correction note for details. Also, ref. 29 was
      incorrectly included in the reference list; it has now been removed.

PMID- 30291316
TI  - Genetic Variations Linked to Hepatocellular Carcinoma: Personalized Medicine
      Takes a Step Forward.
AB  - : There are strong associations between candidate genetic polymorphisms
      associated with intrahepatocyte lipid droplet accumulation and the development of
      cirrhosis, via a common sequence in which lipid accumulation is followed by
      chronic inflammatory injury and fibrogenesis. Hepatocellular carcinoma (HCC) has
      also been linked to genetic polymorphisms associated with intracellular lipid
      trafficking, although, as shown in the present study, not all the candidate
      polymorphisms implicated in fibrogenesis are also tied to HCC. Genetic analysis
      may identify at-risk persons who would most benefit from modifying life-style
      factors linked to cirrhosis and HCC, and also persons most likely to benefit from
      HCC surveillance.

PMID- 30291317
TI  - Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer
      disease.
AB  - Research into dementia prevention is of paramount importance if the dementia
      epidemic is to be halted. Observational studies have identified several
      potentially modifiable risk factors for dementia, including hypertension,
      dyslipidaemia and obesity at midlife, diabetes mellitus, smoking, physical
      inactivity, depression and low levels of education. Randomized clinical trials
      are needed that investigate whether interventions targeting these risk factors
      can reduce the risk of cognitive decline and dementia in elderly adults, but such
      trials are methodologically challenging. To date, most preventive interventions
      have been tested in small groups, have focused on a single lifestyle factor and
      have yielded negative or modest results. Given the multifactorial aetiology of
      dementia and late-onset Alzheimer disease, multidomain interventions that target
      several risk factors and mechanisms simultaneously might be necessary for an
      optimal preventive effect. In the past few years, three large multidomain trials
      (FINGER, MAPT and PreDIVA) have been completed. The FINGER trial showed that a
      multidomain lifestyle intervention can benefit cognition in elderly people with
      an elevated risk of dementia. The primary results from the other trials did not
      show a statistically significant benefit of preventive interventions, but
      additional analyses among participants at risk of dementia showed beneficial
      effects of intervention. Overall, results from these three trials suggest that
      targeting of preventive interventions to at-risk individuals is an effective
      strategy. This Review discusses the current knowledge of lifestyle-related risk
      factors and results from novel trials aiming to prevent cognitive decline and
      dementia. Global initiatives are presented, including the World Wide FINGERS
      network, which aims to harmonize studies on dementia prevention, generate high
      quality scientific evidence and promote its implementation.

PMID- 30291318
TI  - Low rate of necrotizing enterocolitis in extremely low birth weight infants using
      a hospital-based preterm milk bank.
AB  - OBJECTIVE: We examined the effect of two strategies to prevent necrotizing
      enterocolitis (NEC) in extremely low birth weight (ELBW) infants-adherence to a
      standardized feeding protocol and use of a hospital-based milk bank to provide
      exclusive preterm human milk feedings. STUDY DESIGN: We conducted a single-center
      observational study from 2010 to 2015. Infants received preterm human milk,
      initially trophic feeds from days 7 to 14 after birth, followed by advancement of
      15 mL/kg/day to reach a goal of 180 mL/kg/day. Fortification was used selectively
      for weight gain < 15 g/kg/day. We determined the incidence of NEC, other
      morbidities, and growth. RESULTS: The cohort included 398 ELBW infants who
      survived to day 14 without congenital anomalies. Mean gestational age was 26.2 +/
      1.9 weeks. Maternal milk was used as the sole feeding in 62% of infants; preterm
      donor milk was used solely or as supplement in 29%. Full feeds were reached at a
      median of 27 (IQR 23, 33) days. Four infants (1%) developed NEC. CONCLUSION: Use
      of standardized feedings with a hospital-based milk bank is associated with an
      incidence of NEC lower than previously reported.

PMID- 30291319
TI  - Hyaline membrane disease (HMD): an historical and Oslerian perspective.
AB  - Hyaline membrane disease (HMD) offers an illustration of a disease discovered
      during the lifetime of William Osler and effectively treated in the twentieth
      century-the perspective that suggests that there was a straightforward
      progressive identification of the disease process, a discovery of the underlying
      biochemical agent responsible for the pathophysiology, and the pharmacological
      refinement of that agent to be used to treat the disease is illusory. By
      reviewing the timeline from the earliest pathological description of what was to
      be later termed HMD to the discovery of surfactant and its impact on infant
      mortality, this narrative will demonstrate how various random historical events
      served to affect the progress of developing a treatment for HMD; how the marked
      reduction in deaths due to HMD may have set the stage for unrealistic
      expectations; and how the humanities have warned us of the potential for
      excessive optimism in our understanding of nature.

PMID- 30291320
TI  - Does inhaled budesonide for bronchopulmonary dysplasia affect the
      neurodevelopmental outcomes?

PMID- 30291321
TI  - Tidal volume monitoring during emergency neonatal transport.
AB  - OBJECTIVE: The study aim was to identify the frequency with which tidal volumes
      were achieved in a target range in infants requiring positive pressure
      ventilation on emergency transport. STUDY DESIGN: We performed a prospective
      observational study of infants requiring continued positive pressure ventilation
      during emergency transport after resuscitation and stabilization. Blindly
      recorded data were analyzed for percentage of breaths that were below range, in
      range, and above desired range of 4-6 mL/kg. RESULT: Fourteen patients were
      monitored during transport from the delivery room to the neonatal intensive care
      unit, and 15 patients were monitored during inter-facility transport. During
      delivery room transport, 21 and 7% of patients were in target range greater than
      50 and 90% of the time, respectively. During inter-hospital transport, 60 and 7%
      of patients were in target range greater than 50 and 90% of the time,
      respectively. CONCLUSION: Clinical assessment of appropriate ventilation is
      difficult and often inaccurate during emergency neonatal transport. Improved
      monitoring of respiratory function to guide clinical status during transport is
      necessary. More investigation and implementation are urgently needed.

PMID- 30291322
TI  - Development of a points-based system for determining workload for a neonatology
      full-time equivalent.
AB  - Quantifying the workload for a hospital-based physician can be a challenge. We
      developed a novel approach to providing equity and flexibility for physicians
      working in a large system with heterogeneous clinical activities. In developing
      this points-based system, expected clinical work hours were calculated for a full
      time equivalent. A point value was assigned to each clinical service based upon
      the hours, complexity and intensity of the work. A hypothetical work schedule was
      created using the expected clinical hours and translated into points needed for a
      full-time clinician. Faculty appreciate the flexibility and feel appropriately
      valued and equitably paid. Our system serves as a recruitment tool and enables
      the division to better understand resource needs and predict the need for
      additional staff. Development of a point-based model for calculating clinical
      work has successfully created a homogeneous system to define and measure
      physician work expectations in a heterogeneous clinical environment.

PMID- 30291323
TI  - Mitochondrial pyruvate carrier 1 functions as a tumor suppressor and predicts the
      prognosis of human renal cell carcinoma.
AB  - Invasion and subsequent metastasis are major characteristics of malignant human
      renal cell carcinoma (RCC), though the mechanisms remain elusive. Mitochondrial
      pyruvate carrier (MPC), a key factor that controls pyruvate transportation in
      mitochondria, is frequently dysregulated in tumor cells and loss of MPC predicts
      poor prognosis in various types of cancer. However, the clinical relevance and
      functional significance of MPC in RCC remain to be elucidated. In this study, we
      investigated the expression of MPC1 and MPC2 in specimens from RCC patients and
      observed downregulation of MPC1, but not MPC2, in RCC tissues compared with
      adjacent non-cancerous tissue. Moreover, RCC patients with higher MPC1 expression
      exhibited longer overall survival rate than those with lower MPC1. Functionally,
      MPC1 suppressed the invasion of RCC cells in vitro and reduced the growth of RCC
      cells in vivo, possibly through inhibition of MMP7 and MMP9. Further studies
      revealed that loss of MPC1 was induced by hypoxia in RCC cells, and notably, MPC1
      expression, was negatively correlated with HIF1alpha expression in RCC cells and
      patient samples. Taken together, our results identify anti-tumor function of MPC1
      in RCC and revealed MPC1 as a novel prognostic biomarker to predict better
      patient survival.

PMID- 30291324
TI  - First trimester placental endothelial cells from pregnancies with abnormal
      uterine artery Doppler are more sensitive to apoptotic stimuli.
AB  - Failure of the placental capillary network to develop normally is associated with
      early onset fetal growth restriction (FGR) and pre-eclampsia (PE). Although the
      symptoms are observed at term, the problem begins in the first trimester.
      However, investigations at this clinically relevant time are hindered by
      difficulties in identifying earlystage pregnancies that are at risk of developing
      FGR/PE. Using uterine artery Doppler ultrasound in the first trimester as a proxy
      measure of poor placentation, we have identified pregnancies at increased risk of
      developing early onset FGR/PE. Placental endothelial cells (PEC) isolated from
      pregnancies at increased risk of developing FGR/PE grew more slowly and their
      basal rate of apoptosis was significantly higher than that seen in the normal
      group. The pro-apoptotic stimulus, TNFalpha, induced apoptosis in cells from both
      groups but this was significantly greater in the high risk group. TNF receptor
      expression was unaffected. Inhibition of nitric oxide (NO) production
      significantly increased the sensitivity of cells from the normal pregnancies to
      TNFalpha but not in the high risk group establishing a functional role for NO in
      this system. In conclusion, first trimester PEC from pregnancies at increased
      risk of developing early onset FGR/PE were inherently more sensitive to apoptotic
      stimuli and this was functionally linked to the synthesis of NO. This may
      contribute to the poor placental vascular development seen in on going
      pregnancies.

PMID- 30291325
TI  - The cofilin phosphatase slingshot homolog 1 restrains angiotensin II-induced
      vascular hypertrophy and fibrosis in vivo.
AB  - The dual specificity phosphatase slingshot homolog 1 (SSH1) contributes to actin
      remodeling by dephosphorylating and activating the actin-severing protein
      cofilin. The reorganization of the actin cytoskeleton has been implicated in
      chronic hypertension and the subsequent mechano-adaptive rearrangement of vessel
      wall components. Therefore, using a novel Ssh1-/- mouse model, we investigated
      the potential role of SSH1 in angiotensin II (Ang II)-induced hypertension, and
      vascular remodeling. We found that loss of SSH1 did not produce overt phenotypic
      changes and that baseline blood pressures as well as heart rates were comparable
      between Ssh1+/+ and Ssh1-/- mice. Although 14 days of Ang II treatment equally
      increased systolic blood pressure in both genotypes, histological assessment of
      aortic samples indicated that medial thickening was exacerbated by the loss of
      SSH1. Consequently, reverse-transcription quantitative PCR analysis of the
      transcripts from Ang II-infused animals confirmed increased aortic expression
      levels of fibronectin, and osteopontin in Ssh1-/- when compared to wild-type
      mice. Mechanistically, our data suggest that fibrosis in SSH1-deficient mice
      occurs by a process that involves aberrant responses to Ang II-induced TGFbeta1.
      Taken together, our work indicates that Ang II-dependent fibrotic gene expression
      and vascular remodeling, but not the Ang II-induced pressor response, are
      modulated by SSH1-mediated signaling pathways and SSH1 activity is protective
      against Ang II-induced remodeling in the vasculature.

PMID- 30291326
TI  - Single-mode, high-power, mid-infrared, quantum cascade laser phased arrays.
AB  - We demonstrate single-mode, 16-channel, optical phased arrays based on quantum
      cascade laser technology, with emission wavelengths around 4.8 um. The integrated
      device consists of a distributed feedback seed section, a highly-efficient tree
      array multi-mode interferometer power splitter, and a 16-channel amplifier array
      with a 4 degrees  angled facet termination. With a single layer Y2O3 coating, the
      angled facet reflectivity is estimated to be less than 0.1% for suppressing
      amplifier self-lasing. A peak output power of 30 W is achieved with an emission
      spectrum narrower than 11 nm and a side mode suppression ratio over 25 dB. Far
      field distribution measurement result indicates a uniform phase distribution
      across the array output. Using the same phased array architecture, we also
      demonstrate single-mode 3.8 um QCL amplifier arrays with up to 20 W output power.

PMID- 30291327
TI  - Modeling microbial communities from atrazine contaminated soils promotes the
      development of biostimulation solutions.
AB  - Microbial communities play a vital role in biogeochemical cycles, allowing the
      biodegradation of a wide range of pollutants. The composition of the community
      and the interactions between its members affect degradation rate and determine
      the identity of the final products. Here, we demonstrate the application of
      sequencing technologies and metabolic modeling approaches towards enhancing
      biodegradation of atrazine-a herbicide causing environmental pollution. Treatment
      of agriculture soil with atrazine is shown to induce significant changes in
      community structure and functional performances. Genome-scale metabolic models
      were constructed for Arthrobacter, the atrazine degrader, and four other non
      atrazine degrading species whose relative abundance in soil was changed following
      exposure to the herbicide. By modeling community function we show that consortia
      including the direct degrader and non-degrader differentially abundant species
      perform better than Arthrobacter alone. Simulations predict that
      growth/degradation enhancement is derived by metabolic exchanges between
      community members. Based on simulations we designed endogenous consortia
      optimized for enhanced degradation whose performances were validated in vitro and
      biostimulation strategies that were tested in pot experiments. Overall, our
      analysis demonstrates that understanding community function in its wider context,
      beyond the single direct degrader perspective, promotes the design of
      biostimulation strategies.

PMID- 30291328
TI  - Pangenomic comparison of globally distributed Poribacteria associated with sponge
      hosts and marine particles.
AB  - Candidatus Poribacteria is a little-known bacterial phylum, previously
      characterized by partial genomes from a single sponge host, but never isolated in
      culture. We have reconstructed multiple genome sequences from four different
      sponge genera and compared them to recently reported, uncharacterized
      Poribacteria genomes from the open ocean, discovering shared and unique
      functional characteristics. Two distinct, habitat-linked taxonomic lineages were
      identified, designated Entoporibacteria (sponge-associated) and
      Pelagiporibacteria (free-living). These lineages differed in flagellar motility
      and chemotaxis genes unique to Pelagiporibacteria, and highly expanded families
      of restriction endonucleases, DNA methylases, transposases, CRISPR repeats, and
      toxin-antitoxin gene pairs in Entoporibacteria. Both lineages shared pathways for
      facultative anaerobic metabolism, denitrification, fermentation, organosulfur
      compound utilization, type IV pili, cellulosomes, and bacterial proteosomes.
      Unexpectedly, many features characteristic of eukaryotic host association were
      also shared, including genes encoding the synthesis of eukaryotic-like cell
      adhesion molecules, extracellular matrix digestive enzymes, phosphoinositol
      linked membrane glycolipids, and exopolysaccharide capsules. Complete
      Poribacteria 16S rRNA gene sequences were found to contain multiple mismatches to
      "universal" 16S rRNA gene primer sets, substantiating concerns about potential
      amplification failures in previous studies. A newly designed primer set corrects
      these mismatches, enabling more accurate assessment of Poribacteria abundance in
      diverse marine habitats where it may have previously been overlooked.

PMID- 30291329
TI  - Sulfurimonas subgroup GD17 cells accumulate polyphosphate under fluctuating redox
      conditions in the Baltic Sea: possible implications for their ecology.
AB  - The central Baltic Sea is characterized by a pelagic redox zone exhibiting high
      dark CO2 fixation rates below the chemocline. These rates are mainly driven by
      chemolithoautotrophic and denitrifying Sulfurimonas GD17 subgroup cells which are
      motile and fast-reacting r-strategists. Baltic Sea redox zones are unstable and a
      measurable overlap of nitrate and reduced sulfur, essential for chemosynthesis,
      is often only available on small scales and short times due to local mixing
      events. This raises the question of how GD17 cells gain access to electron donors
      or acceptors over longer term periods and under substrate deficiency. One
      possible answer is that GD17 cells store high-energy-containing polyphosphate
      during favorable nutrient conditions to survive periods of nutrient starvation.
      We used scanning electron microscopy with energy-dispersive X-ray spectroscopy to
      investigate potential substrate enrichments in single GD17 cells collected from
      Baltic Sea redox zones. More specific substrate enrichment features were
      identified in experiments using Sulfurimonas gotlandica GD1T, a GD17
      representative. Sulfurimonas cells accumulated polyphosphate both in situ and in
      vitro. Combined genome and culture-dependent analyses suggest that polyphosphate
      serves as an energy reservoir to maintain cellular integrity at unfavorable
      substrate conditions. This redox-independent energy supply would be a
      precondition for sustaining the r-strategy lifestyle of GD17 and may represent a
      newly identified survival strategy for chemolithoautotrophic prokaryotes
      occupying eutrophic redox zones.

PMID- 30291331
TI  - Reviewer Recognition.

PMID- 30291330
TI  - Antiepileptic drug carbamazepine promotes horizontal transfer of plasmid-borne
      multi-antibiotic resistance genes within and across bacterial genera.
AB  - Antibiotic resistance is a severe global threat for public health, causing around
      700,000 deaths per year. Horizontal gene transfer (HGT) is one of the most
      significant pathways to disseminate antibiotic resistance. It is commonly
      acknowledged that sub-minimum inhibition concentrations of antibiotics are major
      contributors in promoting antibiotic resistance through HGT. Pharmaceuticals are
      occurring in our environments at increased levels, yet little is known whether
      non-antibiotic pharmaceuticals cause or accelerate the dissemination of
      antibiotic resistance. Here, we report for the first time that the antiepileptic
      drug, carbamazepine, promotes conjugative transfer of antibiotic resistance
      genes. It was seen that environmentally relevant concentrations of carbamazepine
      (e.g., 0.05 mg/L) significantly enhanced the conjugative transfer of
      multiresistance genes carried by plasmid within and across bacterial genera. The
      underlying mechanisms of the enhanced HGT were revealed by detecting oxidative
      stress and cell membrane permeability, in combination with MinION DNA sequencing,
      genome-wide RNA sequencing, and proteomic analysis. Carbamazepine induced a
      series of acute responses, including increased levels of reactive oxygen species,
      the SOS response; increased cell membrane permeability, and pilus generation.
      Expressional levels of genes related to these processes were significantly
      upregulated during carbamazepine exposure. Given that HGT occurs widely among
      different species in various environments, these findings are an early warning
      for a wide assessment of the roles of non-antibiotic pharmaceuticals in the
      spread of antibiotic resistance.

PMID- 30291332
TI  - Phylogenetics of Mycoplasma hominis clinical strains associated with
      gynecological infections or infertility as disclosed by an expanded multilocus
      sequence typing scheme.
AB  - To our knowledge, the phylodistribution of M. hominis clinical strains associated
      with various pathological conditions of the urogenital tract has not been
      explored hitherto. Here we analyzed the genetic diversity and phylogenetic
      relationships among 59 M. hominis Tunisian clinical isolates, categorized as
      gynecological infections- or infertility-associated pathotypes. For this purpose,
      we developed an expanded multilocus sequence typing (eMLST) scheme, combining the
      previously reported multilocus sequence typing (MLST) loci (gyrB, tuf, ftsY,
      uvrA, gap) with a new selected set of putative virulence genes (p120', vaa, lmp1,
      lmp3, p60), referred herein to as multi-virulence-locus sequence typing (MVLST)
      loci. In doing so, M. hominis population was segregated into two distinct genetic
      lineages, which were differentially associated with each pathotype. Such a clear
      dichotomy was supported by several phylogenetic and population genetic analysis
      tools. Recombination was found to take place, but not sufficient enough to break
      down the overall clonal population structure of M. hominis, most likely as a
      result of purifying selection, which accommodated the most fit clones. In sum,
      and owing to the eMLST scheme described herein, we provide insightful data on the
      phylogenetics of M. hominis, arguing for the existence of genetically
      differentiable urogenital pathotypes.

PMID- 30291333
TI  - Genome-wide association study identifies an acute myeloid leukemia susceptibility
      locus near BICRA.

PMID- 30291334
TI  - Engineering resistance to CD33-targeted immunotherapy in normal hematopoiesis by
      CRISPR/Cas9-deletion of CD33 exon 2.

PMID- 30291335
TI  - Obinutuzumab plus Lenalidomide (GALEN) for the treatment of relapse/refractory
      aggressive lymphoma: a phase II LYSA study.

PMID- 30291337
TI  - Bone marrow hematopoietic dysfunction in untreated chronic lymphocytic leukemia
      patients.
AB  - The consequences of immune dysfunction in B-chronic lymphocytic leukemia (CLL)
      likely relate to the incidence of serious recurrent infections and second
      malignancies that plague CLL patients. The well-described immune abnormalities
      are not able to consistently explain these complications. Here, we report bone
      marrow (BM) hematopoietic dysfunction in early and late stage untreated CLL
      patients. Numbers of CD34+ BM hematopoietic progenitors responsive in standard
      colony-forming unit (CFU) assays, including CFU-GM/GEMM and CFU-E, were
      significantly reduced. Flow cytometry revealed corresponding reductions in
      frequencies of all hematopoietic stem and progenitor cell (HSPC) subsets assessed
      in CLL patient marrow. Consistent with the reduction in HSPCs, BM resident
      monocytes and natural killer cells were reduced, a deficiency recapitulated in
      blood. Finally, we report increases in protein levels of the transcriptional
      regulators HIF-1alpha, GATA-1, PU.1, and GATA-2 in CLL patient BM, providing
      molecular insight into the basis of HSPC dysfunction. Importantly, PU.1 and GATA
      2 were rapidly increased when healthy HSPCs were exposed in vitro to TNFalpha, a
      cytokine constitutively produced by CLL B cells. Together, these findings reveal
      BM hematopoietic dysfunction in untreated CLL patients that provides new insight
      into the etiology of the complex immunodeficiency state in CLL.

PMID- 30291336
TI  - Histone deacetylase inhibitor targets CD123/CD47-positive cells and reverse
      chemoresistance phenotype in acute myeloid leukemia.
AB  - Chemoresistance may be due to the survival of leukemia stem cells (LSCs) that are
      quiescent and not responsive to chemotherapy or lie on the intrinsic or acquired
      resistance of the specific pool of AML cells. Here, we found, among well
      established LSC markers, only CD123 and CD47 are correlated with AML cell
      chemosensitivities across cell lines and patient samples. Further study reveals
      that percentages of CD123+CD47+ cells significantly increased in chemoresistant
      lines compared to parental cell lines. However, stemness signature genes are not
      significantly increased in resistant cells. Instead, gene changes are enriched in
      cell cycle and cell survival pathways. This suggests CD123 may serve as a
      biomarker for chemoresistance, but not stemness of AML cells. We further
      investigated the role of epigenetic factors in regulating the survival of
      chemoresistant leukemia cells. Epigenetic drugs, especially histone deacetylase
      inhibitors (HDACis), effectively induced apoptosis of chemoresistant cells.
      Furthermore, HDACi Romidepsin largely reversed gene expression profile of
      resistant cells and efficiently targeted and removed chemoresistant leukemia
      blasts in xenograft AML mouse model. More interestingly, Romidepsin
      preferentially targets CD123+ cells, while chemotherapy drug Ara-C mainly
      targeted fast-growing, CD123- cells. Therefore, Romidepsin alone or in
      combination with Ara-C may be a potential treatment strategy for chemoresistant
      patients.

PMID- 30291338
TI  - Somatic mutations as markers of outcome after azacitidine and allogeneic stem
      cell transplantation in higher-risk myelodysplastic syndromes.

PMID- 30291339
TI  - A new case of SMA phenotype without epilepsy due to biallelic variants in ASAH1.

PMID- 30291342
TI  - Presymptomatic testing of those at 25% risk of autosomal dominant
      neurodegenerative disease- testing team beware.

PMID- 30291340
TI  - Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects,
      congenital heart defects, and intellectual disability.
AB  - Deletions on chromosome 15q14 are a known chromosomal cause of cleft palate,
      typically co-occurring with intellectual disability, facial dysmorphism, and
      congenital heart defects. The identification of patients with loss-of-function
      variants in MEIS2, a gene within this deletion, suggests that these features are
      attributed to haploinsufficiency of MEIS2. To further delineate the phenotypic
      spectrum of the MEIS2-related syndrome, we collected 23 previously unreported
      patients with either a de novo sequence variant in MEIS2 (9 patients), or a 15q14
      microdeletion affecting MEIS2 (14 patients). All but one de novo MEIS2 variant
      were identified by whole-exome sequencing. One variant was found by targeted
      sequencing of MEIS2 in a girl with a clinical suspicion of this syndrome. In
      addition to the triad of palatal defects, heart defects, and developmental delay,
      heterozygous loss of MEIS2 results in recurrent facial features, including thin
      and arched eyebrows, short alae nasi, and thin vermillion. Genotype-phenotype
      comparison between patients with 15q14 deletions and patients with sequence
      variants or intragenic deletions within MEIS2, showed a higher prevalence of
      moderate-to-severe intellectual disability in the former group, advocating for an
      independent locus for psychomotor development neighboring MEIS2.

PMID- 30291341
TI  - The Global State of the Genetic Counseling Profession.
AB  - The profession of genetic counseling (also called genetic counselling in many
      countries) began nearly 50 years ago in the United States, and has grown
      internationally in the past 30 years. While there have been many papers
      describing the profession of genetic counseling in individual countries or
      regions, data remains incomplete and has been published in diverse journals with
      limited access. As a result of the 2016 Transnational Alliance of Genetic
      Counseling (TAGC) conference in Barcelona, Spain, and the 2017 World Congress of
      Genetic Counselling in the UK, we endeavor to describe as fully as possible the
      global state of genetic counseling as a profession. We estimate that in 2018
      there are nearly 7000 genetic counselors with the profession established or
      developing in no less than 28 countries.

PMID- 30291343
TI  - 1 in 38 individuals at risk of a dominant medically actionable disease.
AB  - Clinical genomic sequencing can identify pathogenic variants unrelated to the
      initial clinical question, but of medical relevance to the patients and their
      families. With ongoing discussions on the utility of disclosing or searching for
      such variants, it is of crucial importance to obtain unbiased insight in the
      prevalence of these incidental or secondary findings, in order to better weigh
      potential risks and benefits. Previous studies have reported a broad range of
      secondary findings ranging from 1 to 9%, merely attributable to differences in
      study design, cohorts tested, sequence technology used and genes analyzed. Here,
      we analyzed WES data of 1640 anonymized healthy Dutch individuals to establish
      the frequency of medically actionable disease alleles in an outbred population of
      European descent. Our study shows that 1 in 38 healthy individuals (2.7%) has a
      (likely) pathogenic variant in one of 59 medically actionable dominant disease
      genes for which the American College of Medical Genetics and Genomics (ACMG)
      recommends disclosure. Additionally, we identified 36 individuals (2.2%) to be a
      carrier of a recessive pathogenic disease allele. Whereas these frequencies of
      secondary findings are in line with what has been reported in the East-Asian
      population, the pathogenic variants are differently distributed across the 59
      ACMG genes. Our results contribute to the debate on genetic risk factor screening
      in healthy individuals and the discussion whether the potential benefits of this
      knowledge and related preventive options, outweigh the risk of the emotional
      impact of the test result and possible stigmatization.

PMID- 30291344
TI  - Identification of a subset of microsatellite-stable endometrial carcinoma with
      high PD-L1 and CD8+ lymphocytes.
AB  - Immune checkpoint blockade has emerged as an effective therapeutic strategy for
      patients with advanced cancer. Identification of biomarkers associated with
      treatment efficacy will help to select patients more likely to respond to this
      approach. High levels of microsatellite instability, tumor expression of PD-L1,
      high tumor mutation burden, and increased tumor-infiltrating lymphocytes have all
      been associated with response to checkpoint inhibitor blockade. The purpose of
      this study was to determine if a subset of microsatellite-stable endometrioid
      endometrial carcinomas have higher immune cell infiltrates and/or expression of
      PD-L1. PD-L1 expression and characterization of immune cell infiltrates were
      analyzed in 132 microsatellite stable, FIGO grade 2 endometrioid carcinomas. PD
      L1 was positive in 48% (63/132) of the tumors. Tumor cell expression of PD-L1 was
      significantly associated with lymphatic/vascular invasion and deep myometrial
      invasion. PD-L1 expression was especially prominent at the invasive front and in
      foci of tumor-associated squamous metaplasia. Twenty-one cases (16% of the total)
      with more diffuse and/or especially strong PD-L1 expression were identified. This
      PD-L1 high subset was associated with significantly higher numbers of tumor
      associated CD3+ and CD8+ lymphocytes. Only one tumor in the PD-L1 high subset
      harbored a POLE mutation. PTEN immunohistochemical loss, a common event in
      endometrioid-type endometrial carcinoma and associated with local immune
      suppression in melanoma, was not associated with PD-L1 expression or
      lymphocyte/macrophage infiltration of the tumor. These results suggest that a
      subset of microsatellite-stable endometrial cancers has higher expression of PD
      L1 and increased tumor-associated CD3+ and CD8+ lymphocytes, characteristics more
      commonly associated with endometrial cancers with high levels of microsatellite
      instability. These results suggest that screening strategies to select only
      microsatellite instability-high advanced endometrial cancers for checkpoint
      inhibitor therapy might exclude patients who could potentially benefit from this
      therapeutic approach.

PMID- 30291345
TI  - Time series analysis of TP53 gene mutations in recurrent HPV-negative vulvar
      squamous cell carcinoma.
AB  - The impact of TP53 gene mutations in recurrent HPV-negative vulvar squamous cell
      carcinomas is unclear. TP53 gene mutations were analyzed in archival tissues of
      24 primary squamous cell carcinoma and local vulvar recurrences arising in
      chronic inflammatory dermatoses by analyzing the full coding sequence of the TP53
      gene and correlated with disease-free survival. After resection of the primary
      squamous cell carcinoma with clear margins 19/24 patients had one and 5/24 had
      multiple recurrences. The first recurrence occurred after median of 46 months
      (range 12-180 months). In all, 17/24 (71%) primary squamous cell carcinomas had
      TP53 gene mutations and recurred after median disease-free intervals of 33 months
      (range 12-180). 14/17 (88%) recurrent squamous cell carcinomas carried again TP53
      gene mutations, five with identical and nine with different, more complex TP53
      gene mutations. 7/24 (29%) patients with a p53 wild-type primary SCC had the
      first recurrence after median 65 months (range 14-144) featuring p53 wild-type in
      3/7 (43%) and TP53 gene mutations in 4/7 (57%) recurrent squamous cell
      carcinomas. Disease-free intervals of > 5 years (60-180 months) were observed in
      10/24 patients total (42%; equally divided among p53 wild-type (5/7; 71%) and
      TP53 gene mutated (5/17; 29%) squamous cell carcinomas). In summary, squamous
      cell carcinomas recurred in the residual vulvar dermatosis independent of TP53
      gene mutational status of the primary squamous cell carcinoma. The majority of
      TP53 gene mutated cancers recurred with different TP53 gene mutations, some of
      them more complex, and patients with p53 wild type developed TP53 gene mutations
      in the recurrent squamous cell carcinomas, possibly indicating increased genetic
      instability in longstanding chronic inflammatory dermatoses. A change of TP53
      gene mutational status after > 5 years suggests de novo oncogenic
      events/carcinogenesis. Longer disease-free intervals in patients with p53 wild
      type primary squamous cell carcinoma suggest that TP53 gene mutational status may
      serve as a prognostic marker for disease-free intervals.

PMID- 30291347
TI  - A novel analytical model of MGMT methylation pyrosequencing offers improved
      predictive performance in patients with gliomas.
AB  - The methylation status of the promoter of MGMT gene is a crucial factor
      influencing clinical decision-making in patients with gliomas. MGMT
      pyrosequencing results are often dichotomized by a cut-off value based on an
      average of several tested CpGs. However, this method frequently results in a
      "gray zone", representing a dilemma for physicians. We therefore propose a novel
      analytical model for MGMT methylation pyrosequencing. MGMT CpG heterogeneity was
      investigated in 213 glioma patients in two tested cohorts: cohort A in which CpGs
      75-82 were tested and cohort B in which CpGs 72-78 were tested. The predictive
      performances of the novel and traditional averaging models were compared in 135
      patients who received temozolomide using receiver operating characteristic curves
      and Kaplan-Meier curves, and in patients stratified according to isocitrate
      dehydrogenase gene mutation status. The results were validated in an independent
      cohort of 65 consecutive patients with high-grade gliomas from the Chinese Glioma
      Genome Atlas database. Heterogeneity of MGMT promoter CpG methylation level was
      observed in most gliomas. The optimal cut-off value for each individual CpG
      varied from 4-16%. The current analysis defined MGMT promoter methylation as
      occurring when at least three CpGs exceeded their respective cut-off values. This
      novel analysis could accurately predict the prognosis of patients in the
      methylation "gray zone" according to the standard averaging method, and improved
      the area under the curves from 0.67, 0.76, and 0.67 to 0.70, 0.84, and 0.72 in
      cohorts A, B, and the validation cohort, respectively, demonstrating superiority
      of this analytical method in all three cohorts. Furthermore, the advantages of
      the novel analysis were retained regardless of WHO grade and isocitrate
      dehydrogenase gene mutation status. In conclusion, this novel analytical model
      offers an improved clinical predictive performance for MGMT pyrosequencing
      results and is suitable for clinical use in patients with gliomas.

PMID- 30291348
TI  - Let there be nano.

PMID- 30291346
TI  - H3K27me3 deficiency defines a subset of dedifferentiated chondrosarcomas with
      characteristic clinicopathological features.
AB  - Dedifferentiated chondrosarcoma is a rare bone sarcoma, whose genetic background
      remains incompletely understood. Mutations in SUZ12 or EED, which encode polycomb
      repressive complex 2 (PRC2) components, and resulting deficiency in H3K27me3 are
      characteristic features of the majority of malignant peripheral nerve sheath
      tumors. Here, we investigated H3K27me3 and PRC2 status in dedifferentiated
      chondrosarcoma. Among 19 evaluable dedifferentiated chondrosarcoma cases, six
      (32%) showed immunohistochemical loss of H3K27me3 only in the dedifferentiated
      component, whereas the well-differentiated component retained H3K27me3. H3K27me3
      deficient dedifferentiated chondrosarcoma occurred in two men and four women with
      a median age of 66. All of these tumors affected bones of the upper half of the
      body, with the ribs being preferentially involved, which represented a
      significantly different distribution compared to that in the 13 H3K27me3-intact
      dedifferentiated chondrosarcomas. H3K27me3-deficient dedifferentiated
      chondrosarcomas were histologically different from H3K27me3-intact
      dedifferentiated chondrosarcomas, as the former invariably demonstrated
      dedifferentiated histology with a striking similarity to classic malignant
      peripheral nerve sheath tumor, comprising sweeping to swirling fascicles of
      relatively uniform spindle cells. Heterologous rhabdomyoblastic differentiation,
      the focal presence of grade 3 chondrosarcoma histology, and a cartilaginous
      component in the metastatic sites were exclusively seen in some cases of H3K27me3
      deficient dedifferentiated chondrosarcoma. In all three H3K27me3-deficient
      dedifferentiated chondrosarcomas that contained focal grade 3 histology,
      dedifferentiated components did not juxtapose to the grade 3 areas but
      transitioned abruptly from the grade 1-2 components. Targeted next generation
      sequencing, which was successfully performed on four H3K27me3-deficient
      dedifferentiated chondrosarcomas, identified an IDH2 mutation in one case and
      COL2A1 truncations in three cases. The dedifferentiated areas of three cases
      harbored SUZ12 or EED alterations, which were absent in the well-differentiated
      component, suggesting a role for PRC2 aberrations in dedifferentiation. H3K27me3
      deficiency defines a novel subset of dedifferentiated chondrosarcoma that
      requires recognition because of its diagnostic and potential clinical
      implications.

PMID- 30291349
TI  - Interfacing nature's catalytic machinery with synthetic materials for semi
      artificial photosynthesis.
AB  - Semi-artificial photosynthetic systems aim to overcome the limitations of natural
      and artificial photosynthesis while providing an opportunity to investigate their
      respective functionality. The progress and studies of these hybrid systems is the
      focus of this forward-looking perspective. In this Review, we discuss how enzymes
      have been interfaced with synthetic materials and employed for semi-artificial
      fuel production. In parallel, we examine how more complex living cellular systems
      can be recruited for in vivo fuel and chemical production in an approach where
      inorganic nanostructures are hybridized with photosynthetic and non
      photosynthetic microorganisms. Side-by-side comparisons reveal strengths and
      limitations of enzyme- and microorganism-based hybrid systems, and how lessons
      extracted from studying enzyme hybrids can be applied to investigations of
      microorganism-hybrid devices. We conclude by putting semi-artificial
      photosynthesis in the context of its own ambitions and discuss how it can help
      address the grand challenges facing artificial systems for the efficient
      generation of solar fuels and chemicals.

PMID- 30291350
TI  - Damage control.

PMID- 30291351
TI  - A non-trivial junction.

PMID- 30291353
TI  - Semi-artificial photosynthesis.
AB  - Combining the strengths of catalytic biomachineries with those of synthetic
      materials can yield more efficient and durable solar chemical conversion.

PMID- 30291352
TI  - Beyond traditional reactivity models.

PMID- 30291354
TI  - Tricks inside a cage.

PMID- 30291355
TI  - Don't believe everything you read especially in medicine and wine (fake news).

PMID- 30291356
TI  - Author Correction: Parent-of-origin-specific signatures of de novo mutations.
AB  - In the version of this article published, the P values for the enrichment of
      single mutation categories were inadvertently not corrected for multiple testing.
      After multiple-testing correction, only two of the six mutation categories
      mentioned are still statistically significant. To reflect this, the text "More
      specifically, paternally derived DNMs are enriched in transitions in A[.]G
      contexts, especially ACG>ATG and ATG>ACG (Bonferroni-corrected P = 1.3 * 10-2 and
      P = 1 * 10-3, respectively). Additionally, we observed overrepresentation of
      ATA>ACA mutations (Bonferroni-corrected P = 4.28 * 10-2) for DNMs of paternal
      origin. Among maternally derived DNMs, CCA>CTA, GCA>GTA and TCT>TGT mutations
      were significantly overrepresented (Bonferroni-corrected P = 4 * 10-4, P = 5 * 10
      4, P = 1 * 10-3, respectively)" should read "More specifically, CCA>CTA and
      GCA>GTA mutations were significantly overenriched on the maternal allele
      (Bonferroni-corrected P = 0.0192 and P = 0.048, respectively)." Additionally, the
      last sentence to the legend for Fig. 3b should read "Green boxes highlight the
      mutation categories that differ significantly" instead of "Green boxes highlight
      the mutation categories that differ more than 1% of mutation load with a
      bootstrapping P value <0.05." Corrected versions of Fig. 3b and Supplementary
      Table 25 appear with the Author Correction.

PMID- 30291358
TI  - Author Correction: MitoTALEN reduces mutant mtDNA load and restores tRNAAla
      levels in a mouse model of heteroplasmic mtDNA mutation.
AB  - In the version of this article originally published, there was an error in Fig.
      1a. The m.5024C>T mutation, shown as a green T, was displaced by one base. The
      error has been corrected in the print, HTML and PDF versions of this article.

PMID- 30291357
TI  - Publisher Correction: Genomes of 13 domesticated and wild rice relatives
      highlight genetic conservation, turnover and innovation across the genus Oryza.
AB  - This article was not made open access when initially published online, which was
      corrected before print publication. In addition, ORCID links were missing for 12
      authors and have been added to the HTML and PDF versions of the article.

PMID- 30291359
TI  - Publisher Correction: Clinical activity and molecular correlates of response to
      atezolizumab alone or in combination with bevacizumab versus sunitinib in renal
      cell carcinoma.
AB  - In the version of this article originally published, there was an error in Fig.
      2n. The top line of the HR comparison chart originally was Atezo + bev vs sun. It
      should have been Atezo + bev vs atezo. The error has been corrected in the HTML
      and PDF versions of this article.

PMID- 30291360
TI  - A molecular mechanism for calcium-mediated synaptotagmin-triggered exocytosis.
AB  - The regulated exocytotic release of neurotransmitter and hormones is accomplished
      by a complex protein machinery whose core consists of SNARE proteins and the
      calcium sensor synaptotagmin-1. We propose a mechanism in which the lipid
      membrane is intimately involved in coupling calcium sensing to release. We found
      that fusion of dense core vesicles, derived from rat PC12 cells, was strongly
      linked to the angle between the cytoplasmic domain of the SNARE complex and the
      plane of the target membrane. We propose that, as this tilt angle increases,
      force is exerted on the SNARE transmembrane domains to drive the merger of the
      two bilayers. The tilt angle markedly increased following calcium-mediated
      binding of synaptotagmin to membranes, strongly depended on the surface
      electrostatics of the membrane, and was strictly coupled to the lipid order of
      the target membrane.

PMID- 30291361
TI  - Transcription-associated histone pruning demarcates macroH2A chromatin domains.
AB  - The histone variant macroH2A occupies large repressive domains throughout the
      genome; however, mechanisms underlying its precise deposition remain poorly
      understood. Here, we characterize de novo chromatin deposition of macroH2A2 using
      temporal genomic profiling in murine-derived fibroblasts devoid of all macroH2A
      isoforms. We find that macroH2A2 is first pervasively deposited genome wide at
      both steady-state domains and adjacent transcribed regions, the latter of which
      are subsequently pruned, establishing mature macroH2A2 domains. Pruning of
      macroH2A2 can be counteracted by chemical inhibition of transcription. Further,
      locus-specific transcriptional manipulation reveals that gene activation depletes
      pre-existing macroH2A2, while silencing triggers ectopic macroH2A2 accumulation.
      We demonstrate that the FACT (facilitates chromatin transcription) complex is
      required for macroH2A2 pruning within transcribed chromatin. Taken together, we
      have identified active chromatin as a boundary for macroH2A domains through a
      transcription-associated 'pruning' mechanism that establishes and maintains the
      faithful genomic localization of macroH2A variants.

PMID- 30291362
TI  - Structural basis for sigma1 receptor ligand recognition.
AB  - The sigma1 receptor is a poorly understood membrane protein expressed throughout
      the human body. Ligands targeting the sigma1 receptor are in clinical trials for
      treatment of Alzheimer's disease, ischemic stroke, and neuropathic pain. However,
      relatively little is known regarding the sigma1 receptor's molecular function.
      Here, we present crystal structures of human sigma1 receptor bound to the
      antagonists haloperidol and NE-100, and the agonist (+)-pentazocine, at
      crystallographic resolutions of 3.1 A, 2.9 A, and 3.1 A, respectively. These
      structures reveal a unique binding pose for the agonist. The structures and
      accompanying molecular dynamics (MD) simulations identify agonist-induced
      structural rearrangements in the receptor. Additionally, we show that ligand
      binding to sigma1 is a multistep process that is rate limited by receptor
      conformational change. We used MD simulations to reconstruct a ligand binding
      pathway involving two major conformational changes. These data provide a
      framework for understanding the molecular basis for sigma1 agonism.

PMID- 30291364
TI  - Magnetic Resonance Spectroscopy Features of the Visual Pathways in Patients with
      Glaucoma.
AB  - PURPOSE: The aim of the study was to investigate any metabolic changes on
      magnetic resonance spectroscopy (MRS) throughout the visual pathway of the brain
      in patients with glaucoma and a control group and correlate the results with
      clinical findings. MATERIAL AND METHODS: A total of 87 patients were enrolled in
      the study, 30 healthy controls, 25 glaucoma, 16 suspected glaucoma (GS) and 16
      ocular hypertension (OHT) patients. A single voxel MRS on TE 30 ms was performed
      by placing the volume of interest (VOI) on the corpus geniculatum laterale (CGL)
      and primary visual cortex (VC). Peak values of metabolites, such as N-acetyl
      aspartate (NAA), creatine (Cr), choline (Cho) and Myo-inositol (Ins) were
      investigated on MRS. The MRS results were correlated with age, intraocular
      pressure (IOP), retinal nerve fiber length (RNFL), mean deviation (MD) and cup
      disk ratio (CD). RESULTS: The NAA values obtained from the CGL in glaucoma and GS
      cases were lower than the healthy control group. The Cho values at CGL in
      glaucoma were lower than GS and controls. There was a negative correlation
      between NAA values of the VC and CD in glaucoma cases. Additionally, there was a
      negative correlation between age and RNFL in both glaucoma and GS cases.
      CONCLUSION: The use of MRS can reveal neurodegeneration in CGL and VC in patients
      with glaucoma. Depiction of metabolic changes throughout the visual pathways via
      MRS will guide the treatment planning and follow-up in glaucoma and GS cases.

PMID- 30291365
TI  - Prediction of neoepitopes from murine sequencing data.

PMID- 30291366
TI  - Identifying anticancer peptides by using a generalized chaos game representation.
AB  - We generalize chaos game representation (CGR) to higher dimensional spaces while
      maintaining its bijection, keeping such method sufficiently representative and
      mathematically rigorous compare to previous attempts. We first state and prove
      the asymptotic property of CGR and our generalized chaos game representation
      (GCGR) method. The prediction follows that the dissimilarity of sequences which
      possess identical subsequences but distinct positions would be lowered
      exponentially by the length of the identical subsequence; this effect was taking
      place unbeknownst to researchers. By shining a spotlight on it now, we show the
      effect fundamentally supports (G)CGR as a similarity measure or feature
      extraction technique. We develop two feature extraction techniques: GCGR-Centroid
      and GCGR-Variance. We use the GCGR-Centroid to analyze the similarity between
      protein sequences by using the datasets 9 ND5, 24 TF and 50 beta-globin proteins.
      We obtain consistent results compared with previous studies which proves the
      significance thereof. Finally, by utilizing support vector machines, we train the
      anticancer peptide prediction model by using both GCGR-Centroid and GCGR
      Variance, and achieve a significantly higher prediction performance by employing
      the 3 well-studied anticancer peptide datasets.

PMID- 30291363
TI  - XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous
      end joining.
AB  - The Ku70-Ku80 (Ku) heterodimer binds rapidly and tightly to the ends of DNA
      double-strand breaks and recruits factors of the non-homologous end-joining
      (NHEJ) repair pathway through molecular interactions that remain unclear. We have
      determined crystal structures of the Ku-binding motifs (KBM) of the NHEJ proteins
      APLF (A-KBM) and XLF (X-KBM) bound to a Ku-DNA complex. The two KBM motifs bind
      remote sites of the Ku80 alpha/beta domain. The X-KBM occupies an internal pocket
      formed by an unprecedented large outward rotation of the Ku80 alpha/beta domain.
      We observe independent recruitment of the APLF-interacting protein XRCC4 and of
      XLF to laser-irradiated sites via binding of A- and X-KBMs, respectively, to
      Ku80. Finally, we show that mutation of the X-KBM and A-KBM binding sites in Ku80
      compromises both the efficiency and accuracy of end joining and cellular
      radiosensitivity. A- and X-KBMs may represent two initial anchor points to build
      the intricate interaction network required for NHEJ.

PMID- 30291367
TI  - Identification and typing of fish pathogenic species of the genus Tenacibaculum.
AB  - Tenacibaculosis is a major bacterial disease that causes severe fish outbreaks
      and losses and limits the culture of a variety of commercially valuable
      anadromous and marine fish species in Europe, America, Asia and Oceania. Fish
      affected by tenacibaculosis have external lesions and necrosis that affect
      different areas of the body surface, reducing their commercial value. Several
      species of Tenacibaculum have been identified as the causal agent of
      tenacibaculosis in fish, including Tenacibaculum maritimum, Tenacibaculum soleae,
      Tenacibaculum discolor, Tenacibaculum gallaicum, Tenacibaculum dicentrarchi and
      "Tenacibaculum finnmarkense" (quotations marks denote species that have not been
      validly published). Diagnosis of tenacibaculosis is usually based on culture
      dependent detection and identification techniques which are time-consuming and do
      not allow to differentiate closely related species. The development of reliable
      techniques for studying the relationships between members of the genus
      Tenacibaculum and for distinguishing fish-pathogenic species of Tenacibaculum
      genus is, therefore, a key step in understanding the diversity and incidence of
      tenacibaculosis in global aquaculture, designing effective prevention strategies
      and early implementation of infection control measures. In this review, recent
      advances in molecular, serological, proteomic and chemotaxonomic techniques
      developed for the identification and differentiation of Tenacibaculum species, as
      well as for the analysis of their genetic and epidemiological relationships are
      discussed. Key features of current diagnostic methods likely to facilitate
      control and prevention of tenacibaculosis and to avoid the spread of its
      aetiological agents are also outlined.

PMID- 30291368
TI  - Long-term preservation of potato leafroll virus, potato virus S, and potato
      spindle tuber viroid in cryopreserved shoot tips.
AB  - Availability of and easy access to diverse plant viruses and viroids is a
      prerequisite in applied and basic studies related to viruses and viroids. Long
      term preservation of viruses and viroids is difficult. A protocol was described
      for long-term preservation of potato leafroll virus (PLRV), potato virus S (PVS),
      and potato spindle tuber viroid (PSTVd) in cryopreserved shoot tips of potato cv.
      Zihuabai. Shoot regrowth levels following cryopreservation were higher in 1.5 mm
      shoot tips (58-60%) than in 0.5-mm-ones (30-38%). All shoots recovered from 0.5
      mm-shoot tips were PVS- and PSTVd-preserved, but none of them were PLRV
      preserved. Cryopreservation of 1.5-mm-shoot tips resulted in 35% and 100% of PLRV
      and PVS- and PSTVd-preserved shoots. Studies on cell survival patterns and virus
      localization provided explanations to the varying PLRV-preservation frequencies
      produced by cryopreservation of the two sizes of shoot tips. Although
      micropropagation efficiencies were low after 12 weeks of subculture following
      cryopreservation, similar efficiencies were obtained after 16 weeks of subculture
      in pathogen-preserved shoots recovered from cryopreservation, compared with the
      diseased in vitro stock shoots (the control). Pathogen concentrations in the
      three pathogens-preserved shoots analyzed by qRT-PCR were similar to those in
      micropropagated shoots. The three pathogens cryopreserved in shoot tips were
      readily transmitted by grafting and mechanical inoculation to potato plants.
      PLRV, PVS, and PSTVd represent a diverse range of plant viruses and viroid in
      terms of taxonomy and infectious ability. Therefore, shoot tip cryopreservation
      opens a new avenue for long-term preservation of the virus and viroid.

PMID- 30291369
TI  - Effects of chronic kidney disease stage 4, end-stage renal disease, or dialysis
      on the plasma concentrations of ombitasvir, paritaprevir, ritonavir, and
      dasabuvir in patients with chronic HCV infection: pharmacokinetic analysis of the
      phase 3 RUBY-I and RUBY-II trials.
AB  - PURPOSE: To characterize the pharmacokinetics of ombitasvir, paritaprevir,
      ritonavir, dasabuvir, and ribavirin in hepatitis C virus (HCV)-infected patients
      with chronic kidney disease stage 4 (CKD4) or end-stage renal disease (ESRD),
      including those on dialysis, in the open-label phase 3 RUBY-I and RUBY-II
      studies. METHODS: Patients (n = 18 CKD4, n = 68 ESRD) received
      ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily +/- dasabuvir 250 mg
      twice daily +/- ribavirin 200 mg once daily for 12 or 24 weeks. Intensive
      pharmacokinetic samples were collected from ten patients; sparse samples were
      collected from all patients. Arterial and venous samples were collected from
      three patients during hemodialysis. Area under the plasma concentration-time
      curve (AUC) was estimated using noncompartmental analyses for intensive data, and
      steady-state trough concentrations (Ctrough) were obtained from the sparse data.
      Pharmacokinetic results from RUBY-I and RUBY-II were compared empirically to
      historical data. RESULTS: The AUC values of ombitasvir, paritaprevir, ritonavir,
      and dasabuvir were comparable between CKD4 and ESRD patients and were within the
      range of values observed in historical studies; dialysis had no effect on drug
      exposures. Ribavirin was extracted during hemodialysis but had similar exposures
      on dialysis and non-dialysis days. Individual steady-state Ctrough values for
      each drug overlapped between CKD4 and ESRD patients, and values in both groups
      were similar to historical values. CONCLUSION: Plasma concentrations of
      ombitasvir, paritaprevir, ritonavir, and dasabuvir were not altered by renal
      impairment or dialysis, suggesting these agents can be administered to HCV
      infected CKD4 or ESRD patients, including those on dialysis, without dose
      adjustment. TRIAL REGISTRATION: Clinicaltrials.gov identifiers: NCT02207088 (RUBY
      I) and NCT02487199 (RUBY-II).

PMID- 30291370
TI  - Topical atorvastatin 1% for prevention of skin toxicity in patients receiving
      radiation therapy for breast cancer: a randomized, double-blind, placebo
      controlled trial.
AB  - BACKGROUND AND PURPOSE: The purpose of this randomized, placebo-controlled,
      double-blind study was to investigate the preventive effect of topical
      administration of atorvastatin (ATV) on the acute radiation-induced skin toxicity
      in patients with breast cancer. PATIENTS AND METHODS: Seventy breast cancer
      patients were randomly assigned to use topical ATV 1% or placebo gels during
      radiotherapy twice daily. Radiation-induced dermatitis was classified according
      to the radiation therapy oncology group (RTOG) criteria, as well as pain and
      itching were scored according to VAS (visual analogue scale) for 6 weeks of
      treatment. RESULTS: Topical administration of ATV gel during radiotherapy reduced
      significantly radiation-induced breast swelling, itching, and pain in breast
      cancer patients by factors of 1.8, 1.7, and 1.5, respectively. ATV reduced the
      redness caused by radiotherapy in patients as compared with placebo; however,
      this difference was statistically not significant. CONCLUSION: ATV was able to
      reduce significantly itching, breast edema, and pain in patients during
      radiotherapy.

PMID- 30291371
TI  - [Treatment options in juvenile idiopathic arthritis : Part 2: Orthopedics und
      surgery].
AB  - In most cases of juvenile idiopathic arthritis (JIA), disease remission can be
      achieved by a multidisciplinary approach using modern medication. However, JIA is
      currently incurable An interdisciplinary concept is therefore needed for long
      term development of affected joints and tendons. Only early interdisciplinary
      treatment strategies can improve long-term outcomes in patients with a
      complicated disease course or persistent disease activity, thereby delaying or
      even avoiding joint replacement. An early interdisciplinary assessment and
      treatment planning according to surgical orthopedic rheumatology aspects is now
      state of the art and will continue to be in the future, especially in treatment
      refractory disease courses.

PMID- 30291372
TI  - [Therapeutic options in juvenile idiopathic arthritis : Part 1: Nonsurgical
      treatment].
AB  - The treatment of children and adolescents with juvenile idiopathic arthritis
      (JIA) has progressed substantially during recent years. Multiple different
      factors have played a role in this advancement: improved medical treatment due to
      the introduction of new drugs, structural improvements with provision of units
      specializing in childhood rheumatology, multidisciplinary treatment concepts,
      structured educational programs for patients and parents, improved functional
      treatment including sports therapy, and selective surgical and orthopedic
      interventions improving functional capacities. Current treatment strategies in
      JIA are aimed at achieving disease remission, i.e., control of disease activity
      and re-establishment of age-appropriate functional capacities. This review
      summarizes important developments in the conservative treatment of JIA. Part 2
      deals with orthopedic and surgical treatment strategies.

PMID- 30291373
TI  - FDG PET/CT for assessing tumour response to immunotherapy : Report on the EANM
      symposium on immune modulation and recent review of the literature.
AB  - This paper follows the immunotherapy symposium held during the European
      Association of Nuclear Medicine (EANM) 2017 Annual Congress. The biological basis
      of the immune checkpoint inhibitors and the drugs most frequently used for the
      treatment of solid tumours are reviewed. The issues of pseudoprogression
      (frequency, timeline), hyperprogression and immune-related side effects are
      discussed, as well as their implications for patient management. A review of the
      recent literature on the use of FDG PET for assessment of immunotherapy is
      presented, and recommendations are provided for assessing tumour response and
      reporting immune-related side effects with FDG PET based on published data and
      experts' experience. Representative clinical cases are also discussed.

PMID- 30291374
TI  - Metabotropic glutamate receptor subtype 5 is altered in LPS-induced murine
      neuroinflammation model and in the brains of AD and ALS patients.
AB  - PURPOSE: The aim of the present study was to determine the expression levels of
      mGluR5 in different mouse strains after induction of neuroinflammation by
      lipopolysaccharide (LPS) challenge and in the brains of patients with Alzheimer's
      disease (AD) and amyotrophic lateral sclerosis (ALS) post mortem to investigate
      mGluR5 expression in human neurodegenerative diseases. METHODS: C57BL/6 and CD1
      mice were injected intraperitoneally with either 10 mg/kg LPS or saline. mGluR5
      and TSPO mRNA levels were measured after 1 and 5 days by qPCR, and mGluR5 protein
      levels were determined by PET imaging with the mGluR5-specific radiotracer
      [18F]PSS232. mGluR5 expression was evaluated in the post-mortem brain slices from
      AD and ALS patients using in vitro autoradiography. RESULTS: mGluR5 and TSPO mRNA
      levels were increased in brains of C57BL/6 and CD1 mice 1 day after LPS treatment
      and remained significantly increased after 5 days in C57BL/6 mice but not in CD1
      mice. Brain PET imaging with [18F]PSS232 confirmed increased mGluR5 levels in the
      brains of both mouse strains 1 day after LPS treatment. After 5 days, mGluR5
      levels in CD1 mice declined to the levels in vehicle-treated mice but remained
      high in C57BL/6 mice. Autoradiograms revealed a severalfold higher binding of
      [18F]PSS232 in post-mortem brain slices from AD and ALS patients compared with
      the binding in control brains. CONCLUSION: LPS-induced neuroinflammation
      increased mGluR5 levels in mouse brain and is dependent on the mouse strain and
      time after LPS treatment. mGluR5 levels were also increased in human AD and ALS
      brains in vitro. PET imaging of mGluR5 levels could potentially be used to
      diagnose and monitor therapy outcomes in patients with AD and ALS.

PMID- 30291375
TI  - Tetraspanin 1 inhibits TNFalpha-induced apoptosis via NF-kappaB signaling pathway
      in alveolar epithelial cells.
AB  - OBJECTIVE: Tetraspanin family plays an important role in the pathogenesis of
      cancer, but its role in lung fibrosis is unknown. To determine whether
      tetraspanin 1 (TSPAN1), a member of the family, may be involved in the
      pathogenesis of pulmonary fibrosis. METHODS: TNFalpha -stimulated human alveolar
      epithelial (A549) and alveolar epithelial type II cell (AT2) were treated in
      vitro. Murine pulmonary fibrosis model was generated by injection of bleomycin
      (BLM). The expression of TSPAN1 was examined in vivo using the bleomycin-induced
      lung fibrosis model and tissue sample of IPF patients. Then we transfected the
      cells with TSPAN1 siRNA or plasmid and detected the expression changes of related
      proteins and cell apoptosis. RESULTS: In our study, we found that TSPAN1 was
      markedly down-regulated in lung tissue of patients with idiopathic pulmonary
      fibrosis (IPF) and in bleomycin-induced pulmonary fibrosis in mice. We also found
      that TSPAN1 was significantly down-regulated in A549 and primary (AT2) cells
      following exposure to TNFalpha. Meanwhile, TSPAN1 inhibited p-IkappaBalpha, which
      attenuated nuclear NF-kappaB translocation and activation and inhibited
      apoptosis. We demonstrated that TSPAN1 reduced Bax translocation and caspase-3
      activation, inhibited the apoptosis by regulating the NF-kappaB pathway in
      response to TNFalpha. CONCLUSIONS: We conclude that TSPAN1 mediated apoptosis
      resistance of alveolar epithelial cells by regulating the NF-kappaB pathway.
      TSPAN1 may be a potential therapeutic target for pulmonary fibrosis or acute lung
      injury.

PMID- 30291376
TI  - Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins
      for acutely injured lungs from sepsis (SAILS) study.
AB  - PURPOSE: Using latent class analysis (LCA), we have consistently identified two
      distinct subphenotypes in four randomized controlled trial cohorts of ARDS. One
      subphenotype has hyper-inflammatory characteristics and is associated with worse
      clinical outcomes. Further, within three negative clinical trials, we observed
      differential treatment response by subphenotype to randomly assigned
      interventions. The main purpose of this study was to identify ARDS subphenotypes
      in a contemporary NHLBI Network trial of infection-associated ARDS (SAILS) using
      LCA and to test for differential treatment response to rosuvastatin therapy in
      the subphenotypes. METHODS: LCA models were constructed using a combination of
      biomarker and clinical data at baseline in the SAILS study (n = 745). LCA
      modeling was then repeated using an expanded set of clinical class-defining
      variables. Subphenotypes were tested for differential treatment response to
      rosuvastatin. RESULTS: The two-class LCA model best fit the population. Forty
      percent of the patients were classified as the "hyper-inflammatory" subphenotype.
      Including additional clinical variables in the LCA models did not identify new
      classes. Mortality at day 60 and day 90 was higher in the hyper-inflammatory
      subphenotype. No differences in outcome were observed between hyper-inflammatory
      patients randomized to rosuvastatin therapy versus placebo. CONCLUSIONS: LCA
      using a two-subphenotype model best described the SAILS population. The
      subphenotypes have features consistent with those previously reported in four
      other cohorts. Addition of new class-defining variables in the LCA model did not
      yield additional subphenotypes. No treatment effect was observed with
      rosuvastatin. These findings further validate the presence of two subphenotypes
      and demonstrate their utility for patient stratification in ARDS.

PMID- 30291377
TI  - Performance of Doppler-based resistive index and semi-quantitative renal
      perfusion in predicting persistent AKI: results of a prospective multicenter
      study.
AB  - PURPOSE: The Doppler-based resistive index (RI) and semi-quantitative evaluation
      of renal perfusion using color Doppler (SQP) have shown promising results for
      predicting persistent acute kidney injury (AKI) in preliminary studies. This
      study aimed at evaluating the performance of RI and SQP to predict short-term
      renal prognosis in critically ill patients. METHODS: Prospective multicenter
      cohort study including unselected critically ill patients. Renal Doppler was
      performed at admission to the intensive care unit. The diagnostic performance of
      RI and SQP to predict persistent AKI at day 3 was evaluated. RESULTS: Overall,
      371 patients were included, of whom 351 could be assessed for short-term renal
      recovery. Two thirds of the included patients had AKI (n = 233; 66.3%), of whom
      136 had persistent AKI (58.4%). Doppler-based RI was higher and SQP lower in AKI
      patients and according to AKI recovery. Overall performance in predicting
      persistent AKI was however poor with area under ROC curve of respectively 0.58
      (95% CI 0.52-0.64) and 0.59 (95% CI 0.54-0.65) for RI and SQP. Optimal cutoff was
      respectively 0.71 and 2 for RI and SQP. At optimal cutoff, sensitivity and
      specificity were 50% (95% CI 41-58%) and 68% (62-74%) for RI and 39% (32-45%) and
      75% (66-82%) for SQP. CONCLUSION: Although statistically associated with AKI
      occurrence, RI and SQP perform poorly in predicting persistent AKI at day 3.
      Further studies are needed to adequately describe factors influencing Doppler
      based assessment of renal perfusion and to delineate whether these indicators may
      be useful at the bedside. CLINICALTRIAL.GOV: NCT02355314.

PMID- 30291378
TI  - Mechanical power of ventilation is associated with mortality in critically ill
      patients: an analysis of patients in two observational cohorts.
AB  - PURPOSE: Mechanical power (MP) may unify variables known to be related to
      development of ventilator-induced lung injury. The aim of this study is to
      examine the association between MP and mortality in critically ill patients
      receiving invasive ventilation for at least 48 h. METHODS: This is an analysis of
      data stored in the databases of the MIMIC-III and eICU. Critically ill patients
      receiving invasive ventilation for at least 48 h were included. The exposure of
      interest was MP. The primary outcome was in-hospital mortality. RESULTS: Data
      from 8207 patients were analyzed. Median MP during the second 24 h was 21.4 (16.2
      28.1) J/min in MIMIC-III and 16.0 (11.7-22.1) J/min in eICU. MP was independently
      associated with in-hospital mortality [odds ratio per 5 J/min increase (OR) 1.06
      (95% confidence interval (CI) 1.01-1.11); p = 0.021 in MIMIC-III, and 1.10 (1.02
      1.18); p = 0.010 in eICU]. MP was also associated with ICU mortality, 30-day
      mortality, and with ventilator-free days, ICU and hospital length of stay. Even
      at low tidal volume, high MP was associated with in-hospital mortality [OR 1.70
      (1.32-2.18); p < 0.001] and other secondary outcomes. Finally, there is a
      consistent increase in the risk of death with MP higher than 17.0 J/min.
      CONCLUSION: High MP of ventilation is independently associated with higher in
      hospital mortality and several other outcomes in ICU patients receiving invasive
      ventilation for at least 48 h.

PMID- 30291380
TI  - Impact of mode of delivery of twins on the pelvic floor 3 and 12 months post
      partum-part II.
AB  - INTRODUCTION AND HYPOTHESIS: To compare the impact of vaginal delivery (VD)
      versus cesarean section (CS) on the pelvic floor in twin primiparae at 3 and 12
      months postpartum. METHODS: This comparative multicenter prospective cohort from
      a large French national cohort study consisted of primiparas who gave birth to
      live twins after 34 weeks of gestation. The primary end point was the postnatal
      urinary incontinence rate 3 months postpartum. The secondary end points were the
      pelvic floor dysfunction (PFD) at 3 and 12 months based on PFDI-20, PFIQ-7, PISQ
      12, and SF-12 responses. RESULTS: A total of 2812 patients in 172 French
      maternity units were recruited between February 2014 and March 2015: 1076 (38%)
      responded at 3 and 12 months (61% at 3 months); 1155 were analyzed at 3 months
      (556 VD and 599 CS) and 800 at 12 months (394 VD and 406 CS). VD was associated
      with more symptoms at 3 months [median PFDI-20 score 25/300 (8-50) vs. 17/300 (4
      36) after CS; p < 0.0001]. Vaginal bulge was more frequently reported after VD (9
      vs. 4%; p = 0.0015). Abdnormal PFD-related quality-of-life scores (scores > 0)
      were more frequent after VD at 3 months (58 vs. 42%; p < 0.0001) and 12 months
      (57 vs. 43%; p = 0.0020), indicating greater discomfort. However, SF-12 scores
      were higher after VD [56 (53-59) vs. 55 (51-58)] at 12 months, indicating better
      general quality of life. CONCLUSIONS: Mode of delivery is significantly
      associated with pelvic organ prolapse symptoms 3 months postpartum, which regress
      by 12 months, probably because of the known spontaneous postnatal improvement of
      PFDs.

PMID- 30291381
TI  - Diagnostic yield of head CT in pediatric emergency department patients with acute
      psychosis or hallucinations.
AB  - BACKGROUND: Children presenting to the emergency department with acute psychosis
      or hallucinations sometimes undergo a head CT to evaluate for a causative lesion.
      The diagnostic yield of head CT in this scenario has not been reported.
      OBJECTIVE: To determine the yield for head CT in children with acute psychosis or
      hallucinations. MATERIALS AND METHODS: We retrospectively searched the radiology
      report database over a 7.5-year period for head CT reports for pediatric
      emergency department patients using the following keywords: hallucination,
      psychosis, psychotic or "hearing voices." All reports were categorized as normal
      or abnormal, and we reviewed and categorized the abnormal cases. We calculated
      the 95% confidence interval for abnormal CTs using the method of Clopper and
      Pearson. RESULTS: We identified 397 pediatric emergency department head CTs. We
      excluded one non-diagnostic exam. We excluded 34 additional cases (which were all
      normal) because of clinical indications that might have independently triggered a
      head CT. Of the remaining 362 cases, 12 reports described abnormalities or
      variants and we reviewed them individually. Based on consensus review, four were
      normal, four had congenital malformations, three had encephalomalacia versus
      demyelination and one demonstrated cortical atrophy. There were no cases with
      actionable findings such as mass, hemorrhage, infection or hydrocephalus. The 95%
      confidence interval for a CT demonstrating causative findings was calculated at 0
      0.82%. CONCLUSION: In the absence of concerning factors such as focal
      neurological deficits, evidence of central nervous system infection, trauma or
      headache, routine screening head CT might not be warranted in children presenting
      with acute psychosis or hallucinations.

PMID- 30291379
TI  - Early PREdiction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis
      cohort study.
AB  - PURPOSE: Reliable biomarkers for predicting subsequent sepsis among patients with
      suspected acute infection are lacking. In patients presenting to emergency
      departments (EDs) with suspected acute infection, we aimed to evaluate the
      reliability and discriminant ability of 47 leukocyte biomarkers as predictors of
      sepsis (Sequential Organ Failure Assessment score >= 2 at 24 h and/or 72 h
      following ED presentation). METHODS: In a multi-centre cohort study in four EDs
      and intensive care units (ICUs), we standardised flow-cytometric leukocyte
      biomarker measurement and compared patients with suspected acute infection
      (cohort-1) with two comparator cohorts: ICU patients with established sepsis
      (cohort-2), and ED patients without infection or systemic inflammation but
      requiring hospitalization (cohort-3). RESULTS: Between January 2014 and February
      2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively.
      Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate
      between the three cohorts. Discriminant analyses for predicting sepsis within
      cohort-1 were undertaken for eight neutrophil (cluster of differentiation
      antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte
      (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker
      (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23-2.57);
      P = 0.002], higher monocyte CD279 [1.32 (1.03-1.70); P = 0.03], and lower
      monocyte HLA-DR [0.73 (0.55-0.97); P = 0.03] expression were associated with
      subsequent sepsis. With logistic regression the optimum biomarker combination was
      increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR
      expression, but no combination had clinically relevant predictive validity.
      CONCLUSIONS: From a large panel of leukocyte biomarkers, immunosuppression
      biomarkers were associated with subsequent sepsis in ED patients with suspected
      acute infection. CLINICAL TRIAL REGISTRATION: NCT02188992.

PMID- 30291382
TI  - Technical success and outcomes in pediatric patients undergoing transjugular
      intrahepatic portosystemic shunt placement: a 20-year experience.
AB  - BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) placement has
      been extensively studied in adults. The experience with TIPS placement in
      pediatric patients, however, is limited. OBJECTIVE: The purpose of this study was
      to report technical success and clinical outcomes in pediatric patients
      undergoing TIPS placement. MATERIALS AND METHODS: Twenty-one children - 12 (57%)
      boys and 9 (43%) girls, mean age 12.1 years (range, 2-17 years) - underwent TIPS
      placement from January 1997 to January 2017. Etiologies of hepatic dysfunction
      included biliary atresia (n=5; 24%), cryptogenic cirrhosis (n=4; 19%), portal or
      hepatic vein thrombosis (n=4, 14%), autosomal-recessive polycystic kidney disease
      (n=3; 14%), primary sclerosing cholangitis (n=2; 10%) and others (n=3, 14%).
      Indications for TIPS placement included variceal hemorrhage (n=20; 95%) and
      refractory ascites (n=1; 5%). Technical success, manometry findings, stent type,
      hemodynamic success, complications, liver enzymes, and clinical outcomes were
      recorded. RESULTS: TIPS placement was technically successful in 20 of 21 (95%)
      children, with no immediate complications. Mean pre- and post-TIPS portosystemic
      gradient was 18.5+/-10.7 mmHg and 7.1+/-3.9 mmHg, respectively. Twenty-two total
      stents were successfully placed in 20 children. Stents used included: Viatorr
      (n=9; 41%), Wallstent (n=7; 32%), Express (n=5; 23%), and iCAST (n=1; 5%). All
      children had resolution of variceal bleeding or ascites. TIPS revision was
      required in 9 (45%) children, with a mean of 2.2 revisions. Hepatic
      encephalopathy developed in 10 children (48%), at a mean of 223.7 days following
      TIPS placement. During the study, 6 (29%) children underwent liver
      transplantation. CONCLUSION: TIPS placement in pediatric patients has high
      technical success with excellent resolution of variceal hemorrhage and ascites.
      TIPS revision was required in nearly half of the cohort, with hepatic
      encephalopathy common after shunt placement.

PMID- 30291383
TI  - Association of miR-146a Gene Polymorphism at loci rs2910164 G/C, rs57095329 A/G,
      and rs6864584 T/C with Susceptibility to Kawasaki Disease in Chinese Children.
AB  - OBJECTIVE: To investigate the genetic association of miR-146a gene polymorphisms
      at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C in patients with
      Kawasaki disease (KD) and coronary artery lesions (CAL). METHODS: There were 120
      patients with KD and 126 healthy subjects in this study. The genotype of loci
      rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C of miR-146a gene were detected
      by polymerase chain reaction-sequence-based typing. RESULTS: For miR-146a gene
      polymorphisms at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C, there
      were no significant difference of genotype frequencies and allele frequencies
      between KD group and healthy control group, or between the IVIG-resistant group
      and IVIG-sensitive group (P > 0.05). In KD with coronary artery lesions (KD-CAL)
      group, the genotype frequencies of GG were higher than that in KD without
      coronary artery lesion (KD-WO) group at locus rs2910164 G/C polymorphisms of miR
      146a gene (chi2 = 6.660, P = 0.036), patients with KD carried genotype of GG were
      at 3.636 times higher risk of getting coronary artery lesions than those of non
      carriers (chi2 = 6.455, P = 0.018, OR = 3.636, 95%CI = 1.280-10.262). While there
      was no significant difference of allele frequency of G and C between KD-CAL group
      and KD-WO group (P > 0.05). In KD-CAL group, the allele frequency of A was higher
      than that in KD-WO group at locus rs57095329 A/G polymorphisms of miR-146a gene
      (chi2 = 4.745, P = 0.035), carriers with allele A were at 2.422 times higher risk
      of getting coronary artery lesions than those of non-carriers (chi2 = 4.745, P =
      0.035, OR = 2.422, 95%CI = 1.073-5.465), while there was no significant
      difference of genotype frequency of AA, AG, and GG types between KD-CAL group and
      KD-WO group (P > 0.05). There was no significant difference of genotype
      frequencies of TT, TC, and CC types and allele frequencies of T and C types
      between KD-CAL group and KD-WO group at locus rs6864584 T/C polymorphisms of miR
      146a gene (P > 0.05). CONCLUSIONS: The significant association has been found
      between the genotype and allele frequency of the miR-146a gene loci rs2910164 G/C
      and rs57095329 A/G, the genotype GG of rs2910164 G/C, and allele A of rs57095329
      A/G were risk factors for getting coronary artery lesions.

PMID- 30291384
TI  - Mortality and Resource Use Following Cardiac Interventions in Children with
      Trisomy 13 and Trisomy 18 and Congenital Heart Disease.
AB  - We sought to evaluate the mortality, risk factors for mortality, and resource
      utilization following cardiac interventions in trisomy 13 (T13) and 18 (T18)
      children. All T13 and T18 children who underwent a cardiac intervention from
      January 1999 to March 2015 were identified from the Pediatric Health Information
      System database. Data collected included demographics, type of congenital heart
      disease (CHD), cardiac interventions, comorbidities, length of stay (LOS),
      hospital charges, and deaths (within 30 days). Logistic regression analysis was
      used to determine factors associated with mortality. There were 49 (47% females)
      T13 and 140 (67% females) T18 subjects. The two cohorts were similar in
      distribution for race, geographic region, insurance type, and median household
      income. The most common CHD in both groups was a shunt lesion followed by
      conotruncal defects. Compared to T18, the T13 cohort had higher mortality (29%
      vs. 12%), tracheostomies (12% vs. 4%), gastrostomies (18% vs. 6%), and overall
      resource use (P < 0.05 for all). White race (OR 0.23, 95% CI 0.06-0.81) in T13
      and older age (in weeks) at surgery in T18 (OR 0.75, 95% CI 0.64-0.86) were
      associated with lower mortality. A select group of T13 and T18 CHD patients can
      undergo successful cardiac interventions, albeit with a higher mortality and
      resource use. T13 patients have higher mortality and resource use compared to
      T18. In T13 and T18 patients, interventions for CHD may be an acceptable and
      ethical option following a careful individualized selection and counseling by a
      team of experts.

PMID- 30291385
TI  - Clinical Effects of Syncope on Disease Severity and Adverse Outcomes in Children
      with Idiopathic and Heritable Pulmonary Arterial Hypertension.
AB  - Syncope is more common in children with idiopathic pulmonary arterial
      hypertension (PAH) than in adults with PAH. Although syncope is associated with a
      poor prognosis in adult PAH, the clinical effects of syncopal events on disease
      severity and outcome in children have not been carefully investigated. This study
      assessed the prevalence of syncope in pediatric PAH and examined its clinical,
      hemodynamic, and prognostic importance. This retrospective study assessed
      clinical data, including syncope status, from 78 children (37 girls) with
      idiopathic and heritable PAH (median age at diagnosis, 11 years). Patients were
      classified as syncopal or non-syncopal, and clinical data from the two groups
      were compared. The primary outcome was a composite of lung transplantation and
      cardiac mortality. Overall, 31 (38%) children had a history of syncope at
      presentation. Median age at diagnosis, sex ratio, brain natriuretic peptide
      level, and 6-min walk distance at diagnosis did not differ between groups. The
      hemodynamic parameters of initial right heart catheterization were similar
      between the syncope and non-syncope group (mean pulmonary artery pressure, 67
      versus 71 mm Hg; cardiac index, 2.9 versus 2.9 l/min/m2, respectively). There was
      not significantly difference in event-free survival rate between two groups.
      Although syncopal events are common in children with PAH, our findings suggest
      that syncope may not be correlated with disease severity or outcome in pediatric
      PAH.

PMID- 30291386
TI  - An investigation into the kinematics of magnetically driven droplets on various
      (super)hydrophobic surfaces and their application to an automated multi-droplet
      platform.
AB  - Magnetic actuation on digital microfluidic (DMF) platforms may provide a low
      cost, less cumbersome alternative for droplet manipulation in comparison to other
      techniques such as electrowetting-on-dielectric. Precise control of droplets in
      magnetically driven DMF platforms is achieved using a low-friction surface,
      magnetically susceptible material/droplet(s), and an applied magnetic field.
      Superhydrophobic (SH) surfaces offer limited friction for aqueous media as
      defined by their high water contact angles (WCA) (>150 degrees ) and low sliding
      angles (<10 degrees ). The low surface friction of such coatings and materials
      significantly reduces the force required for droplet transport. Here, we present
      a study that examines several actuation parameters including the effects of
      particle and particle-free actuation mechanisms, porous and non-porous SH
      materials, surface chemistry, droplet speed/acceleration, and the presence of
      surface energy traps (SETs) on droplet kinematics. Automated actuation was
      performed using an XY linear stepper gantry, which enabled sequential droplet
      actuation, mixing, and undocking operations to be performed in series. The
      results of this study are applied to a quantitative fluorescence-based DNA assay
      in under 2 min. Graphical abstract ?.

PMID- 30291387
TI  - Alumina/nano-graphite composite as a new nanosorbent for the selective
      adsorption, preconcentration, and determination of chromium in water samples by
      EDXRF.
AB  - Obtaining new nanocomposites with sorption properties towards chromium is highly
      important not only from the environmental point of view but also for developing
      eco-friendly methods of chromium determination. The potential use of aluminum
      oxide-coated nano-graphite (Al2O3/nano-G) as a new nanosorbent in ultrasound
      assisted dispersive micro-solid-phase extraction (DMSPE) for rapid speciation of
      trace chromium(III) and chromium(VI) ions in natural water was evaluated. In the
      developed method, the crucial issue is the new nanocomposite synthesized by
      coating alumina on a nano-graphite surface with sorption properties. Structural
      researches of the nanocomposite were carried out by scanning electron microscopy
      (SEM), powder X-ray diffraction (XRD), and Raman spectroscopy. Maximum adsorption
      capacity of Al2O3/nano-G towards Cr(III) was 32.8 mg g-1. The influence of the
      method's factors like pH, sample volumes, contact time, coexisting ions, and
      humic acid on the recovery of chromium was examined. The nanocomposites have been
      found to be stable and effective as a sorbent in water with high concentrations
      of selected cations and anions present in water as well as in water of various
      pH. Al2O3/nano-G is selective for Cr(III) in presence of Cr(VI). Cr(III) was
      determined by the developed method, total Cr after reduction of Cr(VI) to
      Cr(III), and Cr(VI) was calculated as the difference between total Cr and
      Cr(III). After sorption, the nanocomposite with chromium was collected on 5-mm
      diameter filters and analyzed by energy-dispersive X-ray fluorescence
      spectrometry (EDXRF) to determine the chromium concentration. The method was
      characterized by correlation coefficient 0.999, limit of detection (LOD) 0.04 ng
      mL-1, and relative standard deviation (RSD) 3.5%. Al2O3/nano-G combined with
      proposed DMSPE/EDXRF was verified by analysis of certificate reference material
      of natural water (NIST 1640a). Graphical abstract ?.

PMID- 30291389
TI  - Simultaneous determination of 14 urinary biomarkers of exposure to
      organophosphate flame retardants and plasticizers by LC-MS/MS.
AB  - Organophosphate flame retardants and plasticizers (PFRs) are a group of chemicals
      widely added to consumer products. PFRs are quickly metabolized in the human body
      into two types of metabolites, (1) dialkyl and diaryl phosphate esters (DAPs),
      such as diphenyl phosphate (DPHP) and bis(1,3-dichloro-2-propyl) phosphate
      (BDCIPP); and (2) hydroxylated PFRs (HO-PFRs), such as 1-hydroxy-2-propyl bis(1
      chloro-2-propyl) phosphate (BCIPHIPP) and 2-hydroxyethyl bis(2-butoxyethyl)
      phosphate (BBOEHEP). Existing analytical methods usually focus on DAPs;
      therefore, human biomonitoring data on HO-PFRs remain scarce. In this study, an
      analytical procedure was developed for the simultaneous quantification of
      multiple PFR metabolites in human urine, covering eight DAPs and six HO-PFRs.
      Sample preparation was optimized to include all target compounds using Bond-Elut
      C18 solid-phase extraction cartridges, followed by instrumental analysis based on
      liquid-chromatography coupled to tandem mass spectrometry (LC-MS/MS). Method
      performance was validated according to established guidelines and satisfactory
      results were obtained for all metabolites in terms of recovery, linearity, limits
      of quantification, precision, and accuracy. Recoveries ranged from 87 to 112%.
      Method detection limits from 0.002 ng/mL for 2-ethyl-5-hydroxyhexyl diphenyl
      phosphate (5-HO-EHDPHP) to 0.66 ng/mL for 4-hydroxyphenyl phenyl phosphate (4-HO
      DPHP). Seven PFR metabolites were frequently detected in a small biomonitoring
      study (n = 14), among them bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), di-n
      butyl phosphate (DNBP), 5-HO-EHDPHP, and BBOEHEP. Highest mean concentrations
      were found for DPHP, 2-ethylhexyl phenyl phosphate (EHPHP), and BCIPHIPP, while 4
      HO-DPHP, 5-HO-EHDPHP, and EHPHP were detected in urine for the first time.
      Overall, the obtained results demonstrate that the developed method can be used
      for the simultaneous determination of 14 urinary biomarkers of exposure to PFRs.
      Graphical abstract ?.

PMID- 30291390
TI  - Jin-Ming Lin (Ed.): Cell analysis on microfluidics.

PMID- 30291388
TI  - Phenotyping the genus Hypericum by secondary metabolite profiling: emodin vs.
      skyrin, two possible key intermediates in hypericin biosynthesis.
AB  - A wide range of compounds that occur in the genus Hypericum are listed as
      effective drugs of natural origin. The main biological activities of several
      Hypericum representatives are due to the presence of naphthodianthrones,
      phloroglucinols, and other diverse groups of secondary metabolites that
      synergistically contribute to their therapeutic effects. The regulation of
      biosynthesis of hypericin as the key bioactive naphthodianthrone remains
      uncertain. Here, we present liquid chromatography mass spectrometry-based
      phenotyping of 17 Hypericum species, the results of which suggest an important
      role for skyrin and its derivatives in the polyketide pathway that leads to
      hypericin formation. Moreover, we report for the first time the presence of new
      metabolites in the genus Hypericum that are related to classes of anthraquinones,
      their derivatives, and phloroglucinols. As skyrin and other species of
      anthraquinones are rarely found in higher plants but frequently occur in fungal
      microorganisms, the obtained results suggest that further research on the
      synthesis pathways of hypericin and the role of anthraquinone derivatives in
      plant metabolism should be carried out. The fact that these compounds are
      commonly synthesized in endophytic fungi and perhaps there is some similarity in
      the metabolic pathways between these organisms should also be investigated.

PMID- 30291391
TI  - Robotic-assisted versus standard unicompartmental knee arthroplasty-evaluation of
      manuscript conflict of interests, funding, scientific quality and bibliometrics.
AB  - PURPOSE: Robotic-assisted unicompartmental knee arthroplasty (UKA) has gained
      popularity over the last decade claiming enhanced surgical precision and better
      joint kinematics, with peer-reviewed publications about this new technology also
      increasing over the past few years. The purpose of our study was to compare
      manuscripts about robotic-assisted UKA to those about standard UKA in terms of
      industry funding, author conflict of interest, scientific quality, and
      bibliometrics. METHODS: A systematic search using PRISMA guidelines on PubMed and
      Google Scholar from 2012 to 2016 resulted in 45 papers where robotic technology
      was performed for UKA and 167 papers that UKA were performed without the
      assistance of a robot. Between the two groups, we compared (1) rate of
      manuscripts with reported conflict of interest or industry funding, (2) journal
      impact factor, (3) level of evidence, and (4) relative citation ratio. RESULTS:
      Fifty-one percent (23/45) of robotic UKA manuscripts were industry-funded or had
      authors with financial conflict of interest, compared to 29% ([49/167], p < 0.01)
      of non-robotic UKA papers. Significantly more robotic UKA papers (24% [11/45] vs
      9% [16/167), p < 0.01) were published in journals that were not assigned an
      impact factor by the Journal Citations Report. There was no difference in regard
      to bibliometrics or level of evidence. CONCLUSION: Manuscripts in which UKA was
      performed with the assistance of a robot were more likely to be industry funded
      or be written by authors with financial conflicts of interest and published in
      less prestigious journals. There were no differences in scientific quality or
      influence between the two groups. Readers analyzing published data should be
      aware of the potential conflicts of interests in order to more accurately
      interpret manuscripts data and conclusions.

PMID- 30291392
TI  - Comment on Tamagawa and Ikeda's reinterpretation of the Goldman-Hodgkin-Katz
      equation : Are transmembrane potentials caused by polarization?

PMID- 30291393
TI  - Interleukin-22 and Its Correlation with Disease Activity in Plaque Psoriasis.
AB  - Psoriasis is a chronic debilitating skin disease with an estimated prevalence
      reaching 2% of the worldwide population. Psoriatic disease is driven by a network
      of complicated reciprocal interactions among innate and adaptive mechanisms of
      immune system with structural components of the skin. Interleukin (IL)-22
      mediates keratinocyte proliferation and epidermal hyperplasia, inhibits terminal
      differentiation of keratinocytes, and induces the production of antimicrobial
      proteins. The aim of this study was the assessment of IL-22 levels and its
      correlation with disease activity in plaque psoriasis. The study group included
      64 patients with mild, moderate and severe psoriasis. Control group was composed
      of 24 sex- and age-matched healthy volunteers. IL-22 concentration was assessed
      in supernatants of T-cell cultures as well as in the plasma of study and control
      group with the use of ELISA method. Statistical analysis showed that
      concentration of IL-22 in cultures exposed to staphylococcal enterotoxin B was
      significantly higher than in control samples (p = 0.005) and cultures treated
      with IL-12 (p = 0.005). Patients with psoriasis presented significantly higher
      concentrations of IL-22 than healthy individuals (p = 0.0000001). In conclusion,
      IL-22 may collaborate with other soluble factors and cells together forming
      inflammatory circuits that otherwise exist as constitutive or inducible pathways
      in normal skin and become pathologically amplificated in psoriasis. Targeting IL
      22 may be promising as a potential therapeutic for plaque psoriasis.

PMID- 30291394
TI  - Biomechanical considerations are crucial for the success of tendon and meniscus
      allograft integration-a systematic review.
AB  - PURPOSE: This systematic review intends to give an overview of the current
      knowledge on how allografts used for the reconstruction of cruciate ligaments and
      menisci are integrated and specifically perform regarding their biomechanical
      function. METHODS: Two reviewers reviewed the PubMed and Central Cochrane library
      with focus on the biomechanical integration of tendon ligament and meniscus
      allografts. The literature search was conducted in accordance with the PRISMA
      statement for reporting systematic reviews and meta-analyses. RESULTS: The
      analysed literature on tendon allografts shows that they are more vulnerable to
      overstretching in the phase of degradation compared to autografts as the
      revascularization process starts later and takes longer. Therefore, to avoid
      excessive graft loads, allografts for cruciate ligament replacement should be
      selected that exhibit much higher failure loads than the native ligaments to
      counteract the detrimental effect of degradation. Further, placement techniques
      should be considered that result in a minimum of strain differences during knee
      joint motion, which is best achieved by near-isometric placement. The most
      important biomechanical parameters for meniscus allograft transplantation are
      secure fixation and proper graft sizing. Allograft attachment by bone plugs or by
      a bone block is superior to circumferential suturing and enables the allograft to
      restore the chondroprotective biomechanical function. Graft sizing is also of
      major relevance, because too small grafts are not able to compensate the knee
      joint incongruity and too large grafts may fail due to extrusion. Only adequate
      sizing and fixation together can lead to a biomechanically functioning allograft.
      The objective assessment of the biomechanical quality of allografts in a clinical
      setting is challenging, but would be highly desirable for monitoring the
      remodelling and incorporation process. CONCLUSIONS: Currently, indicators like ap
      stability after ACL reconstruction or meniscal extrusion represent only indirect
      measures for biomechanical graft integration. These parameters are at best
      clinical indicators of allograft function, but the overall integration properties
      comprising e.g. fixation and graft stiffness remain unknown. Therefore, future
      research should e.g. focus on advanced imaging techniques or other non-invasive
      methods allowing for in vivo assessment of biomechanical allograft properties.

PMID- 30291395
TI  - Cells, soluble factors and matrix harmonically play the concert of allograft
      integration.
AB  - Implantation of allograft tissues has massively grown over the last years,
      especially in the fields related to sports medicine. Beside the fact that often
      no autograft option exists, autograft related disadvantages as donor-site
      morbidity and prolonged operative time are drastically reduced with allograft
      tissues. Despite the well documented clinical success for bone allograft
      procedures, advances in tissue engineering raised the interest in meniscus,
      osteochondral and ligament/tendon allografts. Notably, their overall success
      rates are constantly higher than 80%, making them a valuable treatment option in
      orthopaedics, especially in knee surgery. Complications reported for allografting
      procedures are a small risk of disease transmission, immunologic rejection, and
      decreased biologic incorporation together with nonunion at the graft-host
      juncture and, rarely, massive allograft resorption. Although allografting is a
      successful procedure, improved techniques and biological knowledge to limit these
      pitfalls and maximize graft incorporation are needed. A basic understanding of
      the biologic processes that affect the donor-host interactions and eventual
      incorporation and remodelling of various allograft tissues is a fundamental
      prerequisite for their successful clinical use. Further, the importance of the
      interaction of immunologic factors with the biologic processes involved in
      allograft incorporation has yet to be fully dissected. Finally, new tissue
      engineering techniques and use of adjunctive growth factors, cell based and
      focused gene therapies may improve the quality and uniformity of clinical
      outcomes. The aim of this review is to shed light on the biology of meniscus,
      osteochondral and ligament/tendon allograft incorporation and how collection and
      storage techniques may affect graft stability and embodiment.Level of evidence V.

PMID- 30291396
TI  - Anatomical reconstruction produced similarly favorable outcomes as repair
      procedures for the treatment of chronic lateral ankle instability at long-term
      follow-up.
AB  - PURPOSE: The aim of this study was to compare long-term outcomes after anterior
      talofibular ligament (ATFL) and calcaneofibular ligament (CFL) repair and
      reconstruction at 5-10 years after surgery. METHODS: Forty-five patients who
      underwent surgical repair or reconstruction of both ATFL and CFL were
      retrospectively investigated in this study. American Orthopedic Foot and Ankle
      Society (AOFAS), Karlsson Score, and Tegner activity scale were used to evaluate
      the ankle function at a follow-up of 5-10 years. Ultrasound examination was used
      to evaluate the ATFL and CFL, and MRI was used to evaluate the cartilage.
      RESULTS: At final follow-up, no patient had recurrent ankle instability. There
      were no significant differences in AOFAS (92.6 +/- 6.5 vs 89.6 +/- 3.4; n.s.) or
      Karlsson Score (93 +/- 8.2 vs 90.6 +/- 5.0; n.s.) between the reconstruction
      group (twenty patients) and the repair group (twenty-five patients)
      postoperatively. There were also no significant differences in activity level as
      measured by the Tegner activity score (6 (range 4 to 8) vs 6 (range 5 to 7);
      n.s.). Five patients in the reconstruction group complained of some tightness of
      the ankles. Ultrasound showed the reconstructed ligaments maintained good
      continuity and were thicker than the repaired ligaments. CONCLUSION: Patients in
      both the repair and the reconstruction cohort had high patient satisfaction with
      the outcomes and high function and activity levels that indicated recreational
      sports participation over a long period. LEVEL OF EVIDENCE: III.

PMID- 30291397
TI  - High tibial osteotomy increases patellofemoral pressure if adverted proximal,
      while open-wedge HTO with distal biplanar osteotomy discharges the patellofemoral
      joint: different open-wedge high tibial osteotomies compared to an extra
      articular unloading device.
AB  - PURPOSE: Valgus high tibial osteotomy (HTO) and a recently introduced extra
      articular absorber have been shown to efficiently unload the medial compartment
      of the knee. However, only little is known about the influence of these treatment
      modalities on biomechanics of the patellofemoral joint. The purpose of this study
      was to investigate and compare the impact of different HTO techniques and
      implantation of an extra-articular absorber on patellofemoral contact forces.
      METHODS: Fourteen fresh frozen cadaveric knees were tested in a specially
      designed knee simulator that allowed simulation of isokinetic flexion-extension
      motions under physiological loading. Mean contact pressure (ACP) and peak contact
      pressure (PCP) of the patellofemoral joint was measured continuously between 0
      degrees  and 120 degrees  of knee flexion using a pressure sensitive film in the
      following conditions: native, after biplanar medial open-wedge HTO with 5 degrees
      and 10 degrees  correction angle performing an ascending frontal osteotomy of
      the tibial tuberosity, and after implantation of an extra-articular absorber
      system (KineSpring(r)). Including a second testing cycle with a biplanar medial
      open-wedge HTO with 5 degrees  and 10 degrees  correction angle performing
      descending frontal osteotomy of the tibial tuberosity. Values after each
      procedure were compared to the corresponding values of the native knee. RESULTS:
      Biplanar proximal osteotomy leaded to a significant increase of retropatellar
      compartment area contact pressure compared to the first untreated test cycle
      (Delta 0.04 +/- 0.01 MPa, p = 0.04). Similar results were observed measuring peak
      contact pressure (Delta 1.41 +/- 0.15 MPa, p = 0.03). With greater correction
      angle 5 degrees , respectively, 10 degrees  peak and contact pressure increased
      accordingly. In contrast, the biplanar distal osteotomy group showed significant
      decrease of pressure values (p = 0.004). The extracapsular, extra-articular
      absorber had no significant influence on pressure levels in the patellofemoral
      joint. CONCLUSION: HTO with a proximal biplanar osteotomy of the tuberositas
      tibia significantly increased patellofemoral pressure conditions depending on the
      correction angle. In contrast a distally directed biplanar osteotomy diminished
      these effects while implantation of an extracapsular, extra-articular absorber
      had no influence on the patellofemoral compartment at all. Consequently, patients
      with varus alignment with additional retropatellar chondropathia should be
      treated with a distally adverted osteotomy to avoid further undesirable pressure
      elevation in the patellofemoral joint.

PMID- 30291398
TI  - Individuals with recurrent ankle sprain demonstrate postural instability and
      neuromuscular control deficits in unaffected side.
AB  - PURPOSE: To compare proprioception, postural stability, and neuromuscular control
      between patients with mechanical laxity and recurrent ankle sprain. METHODS:
      Among 86 patients with ankle instability, 45 patients had mechanical laxity (mean
      age 27.2 +/- 7.0 years) and 41 had recurrent ankle sprain (mean age 25.1 +/- 9.2
      years). Both the affected and unaffected ankles of each patient were evaluated.
      Proprioception and neuromuscular control tests were conducted using an isokinetic
      machine, and postural stability was tested using a postural stabilometry system.
      RESULTS: Proprioception was not significantly different between the unaffected or
      affected ankles of the mechanical laxity group compared with those of the
      recurrent ankle sprain group (n.s). Static and dynamic postural stability and
      neuromuscular control were similar in the affected ankles between the two groups
      (n.s). However, postural stability (static, overall: p = 0.009, anterior
      posterior: p = 0.028, medial-lateral: p = 0.022; dynamic, overall: p = 0.012,
      anterior-posterior: p = 0.004, medial-lateral: p = 0.001) and neuromuscular
      control (inversion: p = 0.031, eversion: p = 0.039, dorsiflexion: p = 0.029,
      plantarflexion: p = 0.035) were significantly decreased in the unaffected ankles
      of the recurrent ankle sprain group compared with those of the mechanical laxity
      group. CONCLUSION: The unaffected ankles of the recurrent ankle sprain group
      showed significant decreases in both postural stability and neuromuscular control
      compared with the mechanical laxity group. Clinicians and therapists should
      consider unaffected ankle rehabilitation in patients with recurrent ankle sprain
      to prevent future sprain events. LEVEL OF EVIDENCE: Case-control study, III.

PMID- 30291399
TI  - A high level of satisfaction after bicompartmental individualized knee
      arthroplasty with patient-specific implants and instruments.
AB  - PURPOSE: Customized Individually Made (CIM) Bicompartmental Knee Arthroplasty
      (BKA) implants and three-dimensional printed customized instruments are available
      to fit to each patient's unique anatomy, medial or lateral with patellofemoral.
      This study aimed to evaluate the clinical outcomes after CIM-BKA. METHODS: Fifty
      five patients [59 knees; average age, 51 years; standard deviation (SD), 6.8;
      range 37-65 years] who underwent CIM-BKA were evaluated over an average of 3.8
      year follow-up (SD 1.6; range 1-6 years). Forty-one knees underwent BKA combined
      medial and patellofemoral replacement (BKA-MP) and 18 knees underwent BKA
      combined lateral with patellofemoral replacement (BKA-LP). Survival rates, the
      modified Cincinnati Knee Rating Scale, WOMAC, VAS, SF-36, a satisfaction survey,
      and radiographic evaluation were used to evaluate outcomes. RESULTS: Overall,
      survival rates were 98% and 92% at 2 and 5 years, respectively. Of 56 knees (95%)
      that did not fail, all patient-reported functional scores significantly improved
      post-operatively (P < 0.01), regardless of the previous surgeries, with a high
      level of satisfaction (51/56 knees, 91%). Radiographically, all the femoral
      components fit perfectly and 56 knees (95%) of the tibial components fit with
      less than 2 mm of undercoverage or overhang. Three knees (5%) required the
      conversion to TKA and 17 knees (29%) required subsequent surgical procedures, of
      which multiply operated knees had higher rate than virgin knee [14/40 (35%) vs.
      3/16 (19%)]. CONCLUSION: CIM-BKA allowed precise fit of the components and
      provided a significant improvement post-operatively with a high level of
      satisfaction over short- to mid-term follow-up. This novel CIM-BKA is
      resurfacing, and does not require 10-mm faceted cuts, being only 3-mm-thick,
      which preserves bone stock for the future. It may be a promising option for
      relatively young active patients with bicompartmental osteoarthritis with a
      longer term follow-up being necessary. LEVEL OF EVIDENCE: IV.

PMID- 30291400
TI  - [Capsaicinoids and cayenne pepper extract].

PMID- 30291401
TI  - Atmospheric PM2.5-Bound Polycyclic Aromatic Hydrocarbons (PAHs) in Guiyang City,
      Southwest China: Concentration, Seasonal Variation, Sources and Health Risk
      Assessment.
AB  - The polycyclic aromatic hydrocarbons (PAHs) bound to fine particulate matter
      (PM2.5) can cause long-term adverse health consequences and are a public concern.
      A total of 144 PM2.5-bound PAHs samples collected from Guiyang City, a typical
      plateau montane area in southwest China, from September 2012 to August 2013 were
      investigated to clarify their concentration, distribution, and potential sources.
      The health exposure risk also was evaluated. The samplers equipped with 90-mm
      glass fibre filters were operated at a flow rate of 100 L min-1 for 24 h. The
      concentrations of the 16 PAHs (US EPA priority) were analysed by using ultra
      performance liquid chromatography equipped with photo diode array detector.
      Diagnostic ratios and back-trajectories were performed for the 16 PAHs sources
      apportionment. The results showed that the 16 PAHs ranged from 2.9 to 231 ng m-3
      with an annual average of 41 +/- 21 ng m-3. The PAHs concentrations exhibited
      obvious seasonal variation, with higher levels in winter than in summer.
      Diagnostic ratios indicated that PAHs mainly originated from the combustion of
      coal and biomass, followed by the emission of vehicle exhaust. Cluster analyses
      on back-trajectories illustrated that approximately 34% of the air mass came from
      abroad, as far as Laos and Vietnam, in summer, whereas more than 90% of the air
      mass came from domestic sources in winter. The lifetime excess cancer risk from
      exposure to PAHs was 3.63 * 10-4, approximately 360 times higher than the health
      guideline (10-6) recommended by the US EPA, reflecting a high risk of cancer.

PMID- 30291402
TI  - Do non-daily smokers compensate for reduced cigarette consumption when smoking
      very-low-nicotine-content cigarettes?
AB  - RATIONALE: The Food and Drug Administration is considering severely restricting
      the nicotine in cigarettes, to reduce smoking. A study showed that non-daily,
      intermittent smokers (ITS) randomized to very-low-nicotine-content cigarettes
      (VLNCCs) reduced their cigarette consumption. OBJECTIVES: To assess whether
      increased smoking intensity of VLNCCs compensated for some of the reduced
      cigarette consumption. METHODS: After a 2-week baseline smoking their own-brand
      cigarettes, 118 ITS were randomized to VLNCCs (~ 1 mg nicotine/g tobacco), and
      120 to normal-nicotine-content cigarettes (NNCCs; ~ 16 mg/g) for 10 weeks.
      Laboratory measures of smoking intensity-total puff volume and carbon monoxide
      (CO) boost-assessed single cigarettes smoked in up to three laboratory topography
      sessions. Field measures assessed returned cigarette butts, averaged over up to
      five 2-week intervals: the mass of tobacco burned (computed from residual mass of
      butts) and the intensity of smoking (by scanning of returned filters). Analysis
      was by mixed model random effects models using baseline values as covariates.
      RESULTS: ITS in the VLNCC group puffed less smoke in topography sessions (-38.50
      mL [-75.21, -1.78]; p < 0.04), but showed no difference in CO boost. Participants
      in the VLNCC group burned 0.02 [0.04, 0.002] grams less tobacco per cigarette (p
      < 0.03). Analysis of filters showed their smoking intensity declined over time,
      compared to NNCC participants (p < 0.04). "Cheating" by smoking normal cigarettes
      did not moderate these effects. CONCLUSIONS: ITS did not increase their smoking
      intensity when switched to VLNCCs; indeed, their smoking intensity decreased.
      Reductions in cigarette consumption seen when ITS are switched to VLNCCs were not
      compensated by increased smoking intensity.

PMID- 30291403
TI  - Social reinstatement: a rat model of peer-induced relapse.
AB  - BACKGROUND: An important factor that can lead to drug relapse is to re-associate
      with drug-using social peers, but there is little literature on the effect of
      social peers on relapse in animal models. METHODS: The current study used a dual
      compartment operant conditioning apparatus that allowed adult male rats to
      respond for cocaine in the presence of a conspecific. In experiment 1, rats were
      trained to self-administer cocaine in the presence of a social peer that was
      separated by a wire screen partition and then that peer was used as a
      reinstatement cue following a period of extinction. In the next experiments, rats
      were trained on alternating sessions to self-administer cocaine in the presence
      of one peer and to self-administer saline in the presence of a different peer
      using either a single-active lever procedure (experiment 2) or a double-active
      lever procedure (experiment 3). Following extinction of responding in the absence
      of the peers, the effect of re-exposure to the cocaine- and saline-associated
      peers on reinstatement of drug seeking was determined. This was tested using both
      single- and double-active lever procedures. RESULTS: In experiment 1, a peer that
      was present throughout cocaine self-administration was able to reinstate cocaine
      seeking following a period of extinction. In experiments 2 and 3, drug seeking
      was reinstated by the cocaine-associated peer (S+), but not the saline-associated
      peer (S-). This discrimination occurred when using either the single-active lever
      procedure or double-active lever procedure. CONCLUSION: These results indicate
      that a social peer can be used as a discriminative stimulus to signal cocaine
      availability and that re-introduction of a peer previously paired with cocaine
      can reinstate cocaine seeking, confirming clinical reports that peer affiliation
      among abstinent cocaine users is an important determinant of relapse.

PMID- 30291404
TI  - Comparison of major complications in children after laparoscopy-assisted
      gastrostomy and percutaneous endoscopic gastrostomy placement: a meta-analysis.
AB  - PURPOSE: A meta-analysis was performed to compare the rates of the major
      complications associated with two gastrostomy tube placement techniques in a
      pediatric population: laparoscopy-assisted gastrostomy (LAG) and percutaneous
      endoscopic gastrostomy (PEG). METHODS: The PubMed electronic database was queried
      for comparative studies of the two insertion techniques. The Newcastle-Ottawa
      scale (NOS) was used for the assessment of the quality and risk of bias in the
      included studies. The main outcome measure was the frequency of major
      complications defined as the need for reoperation within 30 days or death. RevMan
      5.3, was used, with a p < 0.05 indicating statistical significance. RESULTS:
      Eight studies including 1550 patients met the inclusion criteria. The risk for
      major complications was higher in PEG than in LAG 3.86 (95% confidence interval
      1.90-7.81; p < 0.0002). The number needed to treat to reduce one major
      complication by performing LAG instead of PEG was 23. There were no randomized
      controlled trials. Overall, the quality of the included studies was determined to
      be unsatisfactory. CONCLUSIONS: PEG placement was associated with a significantly
      higher risk of major complications compared to LAG placement. Therefore, LAG
      should be the preferred method for gastrostomy tube placement in children.

PMID- 30291405
TI  - [Management of the difficult airway : Overview of the current guidelines].
AB  - Several national airway task forces have recently updated their recommendations
      for the management of the difficult airway in adults. Routinely responding to
      airway difficulties with an algorithm-based strategy is consistently supported.
      The focus is increasingly not on tools and devices but more on good planning,
      preparation and communication. In the case of anticipated airway difficulties the
      airway should be secured when the patient is awake with maintenance of
      spontaneous ventilation. Unaltered a flexible bronchoscopic intubation technique
      is advised as a standard of care in such patients. The importance of maintenance
      of oxygenation is emphasized. Face mask ventilation and the use of supraglottic
      devices are recommended if unexpected airway difficulties occur. Face mask
      ventilation may be facilitated and optimised by early administration of
      neuromuscular blocking agents. If required, in not fastened patients threatened
      by acute hypoxia, carefully applied and pressure-controlled ventilation may
      ensure sufficient oxygenation until the airway is secured. Apnoeic oxygen
      techniques are recommended in high-risk patients and to relieve the time pressure
      of falling oxygen saturation during decision-making processes. The early use of
      video laryngoscopy is advised for endotracheal intubation in the case of failed
      direct laryngoscopy or if intubation is expected to be difficult. For the
      coverage of cannot intubate-cannot oxygenate scenarios, second generation
      supraglottic devices and invasive airway access are advocated. The discussion
      regarding the optimal technique for emergency invasive airway access is still in
      progress. In the case of uncontrollable respiratory deterioration and progressive
      hypoxia, the algorithm must be consistently executed and without delay due to
      ineffective activities (straightforward strategy). Although there is no evidence
      to support the selection of a particular approach, the importance and the need
      for a defined airway concept/algorithm in any anesthesia department is fostered.
      Simplicity and clarity are essential for recall under stressful and time
      sensitive conditions. The algorithm should be adapted to local conditions and
      preferences and devices should be limited to a definite number. The acquisition
      and maintenance of expertise by education and training is demanded.

PMID- 30291407
TI  - [Biopsies of kidney lesions: when and how?]
AB  - The demand for image-guided renal biopsy has increased due to the better
      detection of renal lesions; however, despite modern imaging techniques many small
      renal tumors cannot be classified as benign because they cannot be differentiated
      from renal cell carcinoma. Ultrasound and computed tomography (CT)-guided kidney
      biopsy is a safe and accurate method in the diagnostics of renal lesions and can
      be helpful in the selection of new ablative and pharmaceutical forms of treatment
      and avoid unnecessary operations. This article describes the clinical indications
      for an image-guided biopsy and discusses factors which should be considered when
      performing a biopsy.

PMID- 30291406
TI  - Transcriptional Regulation Between the Two Global Regulators RovA and CRP in
      Yersinia pestis biovar Microtus.
AB  - Yersinia pestis is a dangerous bacterial pathogen that can cause plague. Both
      RovA and cyclic AMP receptor protein (cAMP-CRP) are required for regulating
      biofilm- and virulence-related genes in Y. pestis. In this study, the
      transcriptional regulation between RovA and cAMP-CRP were analyzed by using
      primer extension, quantitative RT-PCR, LacZ fusion, and electrophoretic mobility
      shift assay. The results indicated that RovA repressed crp transcription in an
      indirect manner, while that RovA had no regulatory action on cyaA at the
      transcriptional level. In addition, cAMP-CRP did not regulate the transcription
      of rovA. Taken together with our previous results, complex regulatory
      interactions of RovA, cAMP-CRP, and PhoP/PhoQ in Y. pestis were revealed, which
      would promote us gain deeper understanding about coordinative modulation of
      biofilm- and virulence-related regulator genes.

PMID- 30291409
TI  - ?

PMID- 30291408
TI  - [Imaging of the kidneys and the urinary tract].

PMID- 30291410
TI  - Data sharing improves scientific publication: example of the "hydrops
      initiative".

PMID- 30291411
TI  - Impact of a prolonged interatrial conduction time for predicting the recurrence
      of atrial fibrillation after circumferential pulmonary vein isolation of
      persistent atrial fibrillation.
AB  - There are some cases that are difficult to cure with only circumferential
      pulmonary vein isolation (CPVI) of persistent atrial fibrillation (PerAF).
      Recently, prolonged interatrial conduction times (IACTs), which seem to be
      associated with progressive remodeled atria, have been reported as a predictor of
      new-onset AF. This study aimed to investigate the prognostic value of a prolonged
      IACT for predicting AF recurrences after CPVI of PerAF. One hundred thirteen
      patients who underwent CPVI without an empirical substrate modification of PerAF
      were retrospectively analyzed. The IACT was defined as the interval from the
      earliest P-wave onset on the ECG to the latest activation in the coronary sinus
      and was measured after achieving the CPVI and conversion to sinus rhythm. During
      a mean 22.7-month follow-up after the initial procedure, 56 patients (50%) had AF
      recurrences. Patients with AF recurrence had a longer IACT than those without AF
      recurrence (p < 0.001). The best discriminative cut-off value for the IACT was
      123 ms (sensitivity 53%, specificity 85%). In a Cox multivariate analysis, a
      prolonged IACT of >= 123 ms was the only independent predictor (hazard ratio:
      2.38; 95% confidence interval: 1.36-4.16, p = 0.002) of being associated with the
      incidence of an AF recurrence. Even after multiple CPVI procedures, patients with
      an IACT >= 123 ms had a higher AF recurrence rate than those with an IACT < 123
      ms (p = 0.002). In conclusion, a prolonged IACT of >= 123 ms may be a useful
      marker for predicting AF recurrences after both initial and multiple CPVI
      procedures for PerAF.

PMID- 30291412
TI  - Effect of tofacitinib on the expression of noggin/BMP-4 and hair growth
      stimulation in mice.
AB  - Many hair loss disorders, including non-scaring alopecia, are caused by the
      arrest of hair follicles at the telogen phase, and the failure to enter the
      growth phase. Several studies report the efficacy of tofacitinib in promoting
      hair growth, by mechanisms not precisely known. The aim of this study was to
      identify other mechanisms by which tofacitinib, applied topically, promotes hair
      growth. The results showed that histopathological studies in mice treated
      topically with tofacitinib increased number of hair follicles, ratio of hair
      follicles in anagen phase, and length of hair infundibulum, and a reduced
      interfollicular epidermal thickness, compared to DMSO-treated mice. RT-PCR
      experiments showed significant increases in the expression of noggin (P < 0.05)
      and BMP4 (P < 0.05) mRNAs, which were greater than those in the vehicle
      controlled group. Moreover, the expression of noggin and BMP4 mRNAs was
      significantly higher in the tofacitinib-treated group than in the minoxidil
      treated group. This study would help understand the efficacy and mechanism by
      which tofacitinib, applied topically, triggers noggin and BMP4 mRNA expression,
      both being important molecules involved in the onset of the growth phase of hair
      growth cycles.

PMID- 30291413
TI  - Bite injuries caused by transcranial electrical stimulation motor-evoked
      potentials' monitoring: incidence, associated factors, and clinical course.
AB  - PURPOSE: The incidence of bite injuries associated with transcranial electrical
      stimulation motor-evoked potentials monitoring reportedly ranges from 0.13 to
      0.19%. However, in clinical practice, bite injuries appear to occur more
      frequently than previously reported. Our aim was to identify the incidence of and
      perioperative risk factors associated with bite injuries caused by transcranial
      electrical stimulation motor-evoked potential monitoring. METHODS: Patients who
      underwent elective surgery with transcranial electrical stimulation motor-evoked
      potential monitoring at a single tertiary hospital in Japan between June 2017 and
      December 2017 were included in this study. All patients were assessed by oral
      surgeons preoperatively and postoperatively. The associated factors with bite
      injuries were explored by the univariate analysis. RESULTS: 12 of 186 patients
      experienced 13 bite injuries, including three lip, six oral mucosa, and four
      tongue injuries. No patient required suture repair. 11 of 12 patients had
      uneventful postoperative courses and were cured within 12 postoperative days. One
      patient with a tongue ulcer and a hematoma had difficulty in oral intake and
      persistent dysgeusia. Patient severe movement during transcranial electrical
      stimulation motor-evoked potential monitoring was associated with bite injuries
      (p = 0.03). CONCLUSIONS: The incidence of bite injuries assessed by oral surgeons
      was 6.5% in patients with transcranial electrical stimulation motor-evoked
      potential monitoring, and the patients with severe movement during the monitoring
      tended to incur bite injuries. In rare cases, transcranial electrical stimulation
      motor-evoked potential monitoring may cause difficulty in oral intake and
      dysgeusia.

PMID- 30291414
TI  - Ultrasound-guided quadratus lumborum block in pediatrics: trans-muscular versus
      intra-muscular approach.
AB  - PURPOSE: Quadratus lumborum (QL) block has four approaches. However, there is
      difference between the four approaches regarding efficacy, safety and adverse
      effects. The primary objective of this study is to compare the analgesic effect
      between trans-muscular and intra-muscular approaches of the QL block in pediatric
      patients for elective lower abdominal surgery. METHODS: 54 patients aged between
      1 and 6 years were enrolled. Patients of both genders were selected. The patients
      were randomly classified into two groups: Group TQL includes patients (27
      patients) in whom bilateral QL block was performed using trans-muscular approach,
      and Group IQL (27 patients), which underwent bilateral QL block using an intra
      muscular approach. The primary outcome measure was the number of patients who
      require rescue analgesia in the first 24 h. The secondary outcome measures were
      FLACC score, heart rate, non-invasive blood pressure at 2, 4, 6, 12, and 24 h
      postoperatively, and postoperative complications (e.g., quadriceps muscle
      weakness, local hematoma). RESULTS: In the first 24 h after surgery, 13 patients
      in the IQL group (48.1%) required rescue analgesia, whereas only five patients in
      the TQL group (18.5%) required rescue analgesia. The FLACC score was lower in the
      TQL group than the IQL group at all time intervals up to 24 h postoperatively. In
      the TQL group, eight patients (29.6%) developed quadriceps weakness; whereas,
      only one patient (3.7%) in the IQL group developed quadriceps weakness.
      CONCLUSION: TQL is better than IQL in the analgesic efficacy following the
      pediatric lower laparotomy.

PMID- 30291415
TI  - A dicyclic-type electrode-based biofilm reactor for simultaneous nitrate and
      Cr(VI) reduction.
AB  - A dicyclic-type electrode-based biofilm-electrode reactor (BER) was investigated
      for simultaneous removal of nitrate and Cr(VI). In the absence of Cr(VI), almost
      complete denitrification of 50 mg/L NO3--N was achieved at a very low C/N ratio
      of 0.8 with the optimal current of 50 mA. Cr(VI) was removed by biological
      reduction and co-precipitation when Cr(VI) was taken as the only electron
      acceptor, and the removal efficiencies of Cr(VI) were 99.8%. In the coexistent
      system of nitrate and Cr(VI), nitrate removal was the result of the cooperation
      of hydrogenotrophic denitrification and heterotrophic denitrification. The
      methanol and H2 were also used as electron donors for biological reduction
      Cr(VI). The denitrification process was slightly inhibited by 1.00 mg/L Cr(VI)
      and 94.15% removal efficiency was achieved at current = 50 mA and HRT = 8 h. The
      present results show that the biofilm-electrode reactor is an effective way to
      simultaneous remove co-contaminants.

PMID- 30291416
TI  - The metabolic activity of denitrifying microorganisms accumulating polyphosphate
      in response to addition of fusel oil.
AB  - The effect of distillery waste product (fusel oil) as an alternative external
      organic carbon source (EOCS) was investigated in terms of the metabolic
      properties of denitrifying polyphosphate accumulating organisms (DPAOs). Samples
      of the non-acclimated biomass were collected from a local full-scale wastewater
      treatment plant employing A2/O type bioreactors. The acclimated biomass was
      obtained after cultivation (with fusel oil added) in a bench-scale reactor with a
      process configuration similar to the full-scale bioreactor. Changes in the
      functional properties of the biomass were investigated by measuring the phosphate
      release/uptake rates (PRRs and PURs), and nitrate utilization rates (NURs) with
      fusel oil in anaerobic-anoxic batch tests. Furthermore, a validated extended
      Activated Sludge Model no 2d (ASM2d) was used as a supporting tool to analyze the
      experimental results and estimate the contribution of DPAOs to the overall
      denitrification. In the non-acclimated biomass with fusel oil, the PRRs, PURs and
      NURs were low and close to the rates obtained in a reference test without adding
      EOCS. With the acclimated biomass, the PUR and NUR increased significantly, i.e.,
      3.5 and 2.7 times, respectively. In the non-acclimated biomass, approximately
      60.0 +/- 3.6% and 20.0 +/- 2.2% of the total NUR was attributed to the
      utilization of endogenous carbon and examined EOCS, respectively. The remaining
      portion (20% of the total NUR) was attributed to PHA utilization (linked to PO4-P
      uptake) by DPAOs. With the acclimated biomass, the contribution of the EOCS to
      the NUR increased to approximately 60%, while the contribution of the endogenous
      carbon source decreased accordingly. Very accurate predictions of PURs and NURs
      (R2 = 0.97-1.00) were obtained with the extended ASM2d. Based on model
      simulations, it was estimated that the activity of DPAOs and denitrifying
      ordinary heterotrophic organisms corresponded to approximately 20% and 80% of the
      total NUR, respectively.

PMID- 30291417
TI  - Isolated aggregates of lymphoid cells in the inner bronchial wall in asthma
      patients.
AB  - Here, we report findings in volunteers with bronchial asthma. Biopsies were
      obtained from the inner bronchial wall before and a short time again after
      segmental allergen provocation. In most of the baseline biopsies and in all
      evaluable biopsies after segmental allergen provocation, the follicular lymphoid
      tissue was detected by immunohistochemistry in the epithelium of these asthmatic
      patients. The basic occurrence of the tertiary lymphoid tissue in the bronchial
      mucosa of mild asthmatics was unexpected and may have consequences for the
      interpretation of pathophysiology, e.g., as a cause or consequence of bronchial
      asthma.

PMID- 30291418
TI  - Age-related changes in the temporal focus and self-referential content of
      spontaneous cognition during periods of low cognitive demand.
AB  - An intriguing aspect of human cognition is the unique capacity to mentally
      retreat from our immediate surroundings to consider perspectives distinct from
      the here and now. Despite increasing interest in this phenomenon, relatively
      little is known regarding age-related changes in off-task, self-generated thought
      (often referred to as "mind-wandering"), particularly under conditions of low
      cognitive demand. While a number of studies have investigated the temporal
      orientation of mind-wandering with increasing age, findings have been largely
      inconsistent. Here, we explored the frequency, temporal focus, and self
      referential/social content of spontaneous task-unrelated, perceptually decoupled
      thought in 30 young and 33 healthy older adults using the Shape Expectations
      task, a validated experimental paradigm in which discrete facets of inner
      mentation are quantified along a conceptual continuum using open-ended report.
      Participants also completed the daydreaming subscale of the Imaginal Process
      Inventory (IPI) as a trait measure of mind-wandering propensity. Significant
      group differences emerged on the Shape Expectations task, with reduced instances
      of mind-wandering in the context of elevated task-related thoughts relative to
      younger adults. In terms of temporal focus, a preponderance of present/atemporal
      off-task thoughts was evident irrespective of group; however, significantly
      higher levels of future-oriented thoughts were provided by younger adults,
      contrasting with significantly higher instances of retrospection in the older
      group. In addition, older adults displayed significantly fewer incidences of self
      referential cognition relative to their younger counterparts. Our findings
      indicate a distinct attenuation of off-task, self-generated thought processes
      with increasing age, with evidence for a shift in temporal focus and self
      referential quality, during periods of low cognitive demand.

PMID- 30291419
TI  - Letter to the Editor regarding Morkl et al.'s paper: Gut microbiota, dietary
      intakes and intestinal permeability reflected by serum zonulin in women.

PMID- 30291420
TI  - Response to Letter to the Editor to Gut microbiota, dietary intakes and
      intestinal permeability reflected by serum zonulin in women.

PMID- 30291422
TI  - Age and infection history are revealed by different ornaments in a warbler.
AB  - Female preference for older or more disease-resistant males are both possible
      outcomes of parasite-mediated sexual selection, but the extent to which infection
      alters the development of ornaments to yield signals of male age and health has
      rarely been explored. In a longitudinal study of 61 male common yellowthroats
      (Geothlypis trichas), age-related increases in the size of the melanin-based mask
      and carotenoid-based bib were not correlated among young males, likely owing to
      differences in how blood parasites affect ornament development. Infection with
      trypanosomes and hemosporidians in a male's first breeding season was associated
      with slower growth of the mask; uninfected males attained large masks in their
      second breeding season, while infected males attained large masks in their third
      breeding season. In contrast, the bib size of males increased every year
      regardless of infection. As a consequence, different populations of males are
      identified by the largest ornaments-older males in the case of bib and a
      combination of older males and young, uninfected males in the case of mask.
      Although mask is thus the more informative trait with respect to male health,
      females prefer large bibs in our population. If infection is opportunistic,
      young, uninfected males may not possess good genes for parasite resistance but
      simply good luck, and it may benefit females to prefer older males who are more
      likely to have withstood prior episodes of selection. A "pure" signal of age may
      be a more reliable signal of resistance to parasites than an ornament whose
      expression is modulated by infection.

PMID- 30291421
TI  - Heterochromatin restricts the mobility of nuclear bodies.
AB  - Nuclear bodies are relatively immobile organelles. Here, we investigated the
      mechanisms underlying their movement using experimentally induced interphase
      prenucleolar bodies (iPNBs). Most iPNBs demonstrated constrained diffusion,
      exhibiting infrequent fusions with other iPNBs and nucleoli. Fusion events were
      actin-independent and appeared to be the consequence of stochastic collisions
      between iPNBs. Most iPNBs were surrounded by condensed chromatin, while fusing
      iPNBs were usually found in a single heterochromatin-delimited compartment
      ("cage"). The experimentally induced over-condensation of chromatin significantly
      decreased the frequency of iPNB fusion. Thus, the data obtained indicate that the
      mobility of nuclear bodies is restricted by heterochromatin.

PMID- 30291423
TI  - Comparison of outcome in stroke patients admitted during working hours vs. off
      hours; a single-center cohort study.
AB  - INTRODUCTION: We aimed to disprove an in-hospital off-hour effect in stroke
      patients by adjusting for disease severity and poor prognostic findings on
      imaging. PATIENTS AND METHODS: Our study included 5378 patients from a single
      center prospective stroke registry of a large teaching hospital in the
      Netherlands, admitted between January 2003 and June 2015. Patients were
      categorized by admission time, off-hours (OH) or working hours (WH). The in
      hospital mortality, 7-day mortality, unfavorable functional outcome (modified
      Rankin scale > 2) and discharge to home were analyzed. Results were adjusted for
      age, sex, stroke severity (NIHSS score) and unfavorable findings on imaging of
      the brain (midline shift and dense vessel sign). RESULTS: Overall, 2796 patients
      (52%) were admitted during OH, which had a higher NIHSS score [3 (IQR 2-8) vs. 3
      (IQR 2-6): p < 0.01] and had more often a dense vessel sign at admission (7.9%
      vs. 5.4%: p < 0.01). There was no difference in mortality between the OH-group
      and WH-group (6.2% vs. 6.0%; p = 0.87). The adjusted hazard ratio of in-hospital
      mortality during OH was 0.87 (95% CI: 0.70-1.08). Analysis of 7-day mortality
      showed similar results. Unadjusted, the OH-group had an unfavorable outcome [OR:
      1.14 (95% CI: 1.02-1.27)] and could less frequently be discharged to home [OR:
      1.16 (95% CI: 1.04-1.29)], which was no longer present after adjustment.
      DISCUSSION AND CONCLUSIONS: The overall outcome of stroke patients admitted to a
      large Dutch teaching hospital is not influenced by time of admission. When
      studying OH effects, adjustment for disease severity and poor prognostic findings
      on imaging is crucial before drawing conclusions on staffing and material.

PMID- 30291424
TI  - Cerebral small vessel disease: neuroimaging markers and clinical implication.
AB  - Cerebral small vessel disease (CSVD) is a broad category of cerebrovascular
      diseases which primarily affect the perforating arterioles, capillaries and
      venules with multiple distinct etiologies. In spite of distinctive pathogenesis,
      CSVD shares similar neuroimaging markers, including recent small subcortical
      infarct, lacune of presumed vascular origin, white matter hyperintensity of
      presumed vascular origin, perivascular space and cerebral microbleeds. The
      radiological features of neuroimaging markers are indicative for etiological
      analysis. Furthermore, in sporadic arteriosclerotic pathogenesis associated CSVD,
      the total CSVD burden is a significant predictor for stroke events, global
      cognitive impairment, psychiatric disorders and later life quality. This review
      aims to summarize the radiological characteristics as well as the clinical
      implication of CSVD markers and neuroimaging interpretation for CSVD
      symptomatology.

PMID- 30291425
TI  - Hypoalgesia after bicycling at lactate threshold is reliable between sessions.
AB  - PURPOSE: Exercise decreases pain sensitivity known as exercise-induced
      hypoalgesia (EIH). However, the consistency of EIH after an acute exercise
      protocol based on subjective ratings of perceived exertion has been questioned.
      Objectives were to compare the effect on pressure pain thresholds (PPTs) after
      bicycling with work-rate at the lactate threshold compared with quiet rest, and
      investigate between-session reliability of EIH. METHODS: Thirty-four healthy
      subjects completed three sessions with 7 days in-between. In session 1, the
      lactate threshold was determined via blood samples (finger-tip pinprick, > 2
      mmol/l increase from warm-up) during a graded bicycling task. In session 2 and 3,
      all subjects performed (1) 15 min quiet-rest, and (2) 15 min bicycling (work-rate
      corresponding to the lactate threshold) in the two identical sessions. PPTs at
      the quadriceps and trapezius muscles were assessed before and after both
      conditions. Reliability was assessed by intraclass correlations (ICCs). RESULTS:
      Bicycling increased quadriceps PPT compared with quiet-rest in both sessions
      [mean difference: 45 kPa (95% CI 19-72 kPa), P = 0.002]; however, the increase in
      trapezius PPT was not significant after exercise. The EIH responses demonstrated
      fair between-session test-retest reliability (quadriceps: ICC = 0.45; trapezius:
      ICC = 0.57, P < 0.05), and agreement in EIH responders and non-responders between
      sessions was significant (quadriceps: kappa = 0.46 and trapezius: kappa = 0.43, P
      < 0.05). CONCLUSIONS: In conclusion, bicycling at the lactate threshold increased
      PPT at the exercising muscle with fair reliability of the local EIH response. The
      results have implications for future EIH studies in subjects with and without
      pain and for clinicians who design exercise programs for pain relief.

PMID- 30291426
TI  - iNuc-ext-PseTNC: an efficient ensemble model for identification of nucleosome
      positioning by extending the concept of Chou's PseAAC to pseudo-tri-nucleotide
      composition.
AB  - Nucleosome is a central element of eukaryotic chromatin, which composes of
      histone proteins and DNA molecules. It performs vital roles in many eukaryotic
      intra-nuclear processes, for instance, chromatin structure and transcriptional
      regulation formation. Identification of nucleosome positioning via wet lab is
      difficult; so, the attention is diverted towards the accurate intelligent
      automated prediction. In this regard, a novel intelligent automated model "iNuc
      ext-PseTNC" is developed to identify the nucleosome positioning in genomes
      accurately. In this predictor, the sequences of DNA are mathematically
      represented by two different discrete feature extraction techniques, namely
      pseudo-tri-nucleotide composition (PseTNC) and pseudo-di-nucleotide composition.
      Several contemporary machine learning algorithms were examined. Further, the
      predictions of individual classifiers were integrated through an evolutionary
      genetic algorithm. The success rates of the ensemble model are higher than
      individual classifiers. After analyzing the prediction results, it is noticed
      that iNuc-ext-PseTNC model has achieved better performance in combination with
      PseTNC feature space, which are 94.3%, 93.14%, and 88.60% of accuracies using six
      fold cross-validation test for the three benchmark datasets S1, S2, and S3,
      respectively. The achieved outcomes exposed that the results of iNuc-ext-PseTNC
      model are prominent compared to the existing methods so far notifiable in the
      literature. It is ascertained that the proposed model might be more fruitful and
      a practical tool for rudimentary academia and research.

PMID- 30291427
TI  - Hyperphosphatemia in an 11-year-old girl with acute myeloid leukemia: Questions.

PMID- 30291428
TI  - Hyperphosphatemia in an 11-year-old girl with acute myeloid leukemia: Answers.

PMID- 30291429
TI  - Kidney as modulator and target of "good/bad" HDL.
AB  - The strong inverse relationship between low levels of high-density lipoproteins
      (HDLs) and atherosclerotic cardiovascular disease (CVD) led to the designation of
      HDL as the "good" cholesterol. The atheroprotection is thought to reflect HDL's
      capacity to efflux cholesterol from macrophages, followed by interaction with
      other lipoproteins in the plasma, processing by the liver and excretion into
      bile. However, pharmacologic increases in HDL-C levels have not led to expected
      clinical benefits, giving rise to the concept of dysfunctional HDL, in which
      increases in serum HDL-C are not beneficial due to lost or altered HDL functions
      and transition to "bad" HDL. It is now understood that the cholesterol in HDL,
      measured by HDL-C, is neither a marker nor the mediator of HDL function,
      including cholesterol efflux capacity. It is also understood that besides
      cholesterol efflux, HDL functionality encompasses many other potentially
      beneficial functions, including antioxidant, anti-inflammatory, antithrombotic,
      anti-apoptotic, and vascular protective effects that may be critical protective
      pathways for various cells, including those in the kidney parenchyma. This review
      highlights advances in our understanding of the role kidneys play in HDL
      metabolism, including the effects on levels, composition, and functionality of
      HDL particles, particularly the main HDL protein, apolipoprotein AI (apoAI). We
      suggest that normal apoAI/HDL in the glomerular filtrate provides beneficial
      effects, including lymphangiogenesis, that promote resorption of renal
      interstitial fluid and biological particles. In contrast, dysfunctional apoAI/HDL
      activates detrimental pathways in tubular epithelial cells and lymphatics that
      lead to interstitial accumulation of fluid and harmful particles that promote
      progressive kidney damage.

PMID- 30291430
TI  - In vitro experimental models for examining the skeletal muscle cell biology of
      exercise: the possibilities, challenges and future developments.
AB  - Exercise provides a cornerstone in the prevention and treatment of several
      chronic diseases. The use of in vivo exercise models alone cannot fully establish
      the skeletal muscle-specific mechanisms involved in such health-promoting
      effects. As such, models that replicate exercise-like effects in vitro provide
      useful tools to allow investigations that are not otherwise possible in vivo. In
      this review, we provide an overview of experimental models currently used to
      induce exercise-like effects in skeletal muscle in vitro. In particular, the
      appropriateness of electrical pulse stimulation and several pharmacological
      compounds to resemble exercise, as well as important technical considerations,
      are addressed. Each model covered herein provides a useful tool to investigate
      different aspects of exercise with a level of abstraction not possible in vivo.
      That said, none of these models are perfect under all circumstances, and the
      choice of model (and terminology) used should be informed by the specific
      research question whilst accounting for the several inherent limitations of each
      model. Further work is required to develop and optimise the current experimental
      models used, such as combination with complementary techniques during treatment,
      and thereby improve their overall utility and impact within muscle biology
      research.

PMID- 30291431
TI  - Carbocisteine stimulated an increase in ciliary bend angle via a decrease in [Cl
      ]i in mouse airway cilia.
AB  - Carbocisteine (CCis), a mucoactive agent, is widely used to improve respiratory
      diseases. This study demonstrated that CCis increases ciliary bend angle (CBA) by
      30% and ciliary beat frequency (CBF) by 10% in mouse airway ciliary cells. These
      increases were induced by an elevation in intracellular pH (pHi; the pHi pathway)
      and a decrease in the intracellular Cl- concentration ([Cl-]i; the Cl- pathway)
      stimulated by CCis. The Cl- pathway, which is independent of CO2/HCO3-, increased
      CBA by 20%. This pathway activated Cl- release via activation of Cl- channels,
      leading to a decrease in [Cl-]i, and was inhibited by Cl- channel blockers (5
      nitro-2-(3-phenylpropylamino) benzoic acid and CFTR(inh)-172). Under the CO2/HCO3
      -free condition, the CBA increase stimulated by CCis was mimicked by the Cl--free
      NO3- solution. The pHi pathway, which depends on CO2/HCO3-, increased CBF and CBA
      by 10%. This pathway activated HCO3- entry via Na+/HCO3- cotransport (NBC),
      leading to a pHi elevation, and was inhibited by 4,4'-diisothiocyano-2,2'
      stilbenedisulfonic acid. The effects of CCis were not affected by a protein
      kinase A inhibitor (1 MUM PKI-A) or Ca2+-free solution. Thus, CCis decreased [Cl
      ]i via activation of Cl- channels including CFTR, increasing CBA by 20%, and
      elevated pHi via NBC activation, increasing CBF and CBA by 10%.

PMID- 30291434
TI  - Mitochondrial disorder mimicking rheumatoid disease.
AB  - OBJECTIVE: Mitochondrial disorders (MIDs) may manifest phenotypically with a
      plethora of clinical features, but polyarthralgia and cutaneous lesions are still
      infrequently reported and recognized as phenotypic manifestations of a MID. CASE
      REPORT: The patient is a 27-year-old Caucasian female with a history of preterm
      birth, symptomatic myopathy, and polyarthralgia since infancy, followed by
      multiple endocrinopathies including pituitary insufficiency, cardiac conduction
      defects, nephrolithiasis, aseptic chronic pancreatitis and sialadenitis, anemia,
      hyperlipidemia, and dysmorphic features. The patient reported to have profited
      from hydrocortisone and long-term chloroquine, but hardly from long-term
      immunosuppression with various immunosuppressants. The diagnosis MID was
      established upon the multiorgan nature of the disease, presence of core clinical
      features of a MID, and a muscle biopsy indicative of a mitochondrial defect. The
      family history was positive for mitochondrial features in the mother and
      grandmother from the mother's side. CONCLUSION: Seronegative and non-destructive
      polyarthralgia and unexplained cutaneous features mimicking cutaneous lupus
      should be considered as a phenotypic feature of a multisystem MID (mitochondrial
      multiorgan disorder syndrome, MIMODS). Mitochondrial metabolic defects may
      trigger secondary immune reactions. Core clinical features of a non-specific MID
      with infantile onset include symptomatic myopathy, endocrine abnormalities,
      cardiac conduction defects, dysmorphism, hyperlipidemia, anemia, and
      nephrolithiasis.

PMID- 30291433
TI  - [Pathogenesis of systemic lupus erythematosus].
AB  - The causes of diseases and disorders of the immune system, which lead to the
      development of systemic lupus erythematosus (SLE), are not yet completely
      understood; however, it is known that there are various mechanisms, which can
      lead to SLE. The development of the disease is based on an underlying genetic
      disposition but is first triggered by exposure to environmental factors, such as
      sunburn, viral infections or vitamin D deficiency. Disease flares can also be
      triggered by environmental factors. Many disease manifestations are caused by
      pathogenic autoantibodies; hence, B-cells and plasma cells play a critical role
      in the pathogenesis of SLE. This review provides an overview of the most frequent
      factors leading to the development of SLE and describes the key mechanisms of its
      pathogenesis.

PMID- 30291432
TI  - Implication of non-coding PAX6 mutations in aniridia.
AB  - There is an increasing implication of non-coding regions in pathological
      processes of genetic origin. This is partly due to the emergence of sophisticated
      techniques that have transformed research into gene expression by allowing a more
      global understanding of the genome, both at the genomic, epigenomic and chromatin
      levels. Here, we implemented the analysis of PAX6, whose coding loss-of-function
      variants are mainly implied in aniridia, by studying its non-coding regions
      (untranslated regions, introns and cis-regulatory sequences). In particular, we
      have taken advantage of the development of high-throughput approaches to screen
      the upstream and downstream regulatory regions of PAX6 in 47 aniridia patients
      without identified mutation in the coding sequence. This was made possible
      through the use of custom targeted resequencing and/or CGH array to analyze the
      entire PAX6 locus on 11p13. We found candidate variants in 30 of the 47 patients.
      9/30 correspond to the well-known described 3' deletions encompassing SIMO and
      other enhancer elements. In addition, we identified numerous different variants
      in various non-coding regions, in particular untranslated regions. Among these
      latter, most of them demonstrated an in vitro functional effect using a minigene
      strategy, and 12/21 are thus considered as causative mutations or very likely to
      explain the phenotypes. This new analysis strategy brings molecular diagnosis to
      more than 90% of our aniridia patients. This study revealed an outstanding
      mutation pattern in non-coding PAX6 regions confirming that PAX6 remains the
      major gene for aniridia.

PMID- 30291436
TI  - Reply to the comments on "Macular buckle technique in myopic traction
      maculopathy: a 16-year review of the literature and a comparison with vitreous
      surgery".

PMID- 30291435
TI  - New iPAD-based test for the detection of color vision deficiencies.
AB  - PURPOSE: To develop and validate a new iPad-based color vision test (Optopad).
      METHODS: A total of 341 student eyes were enrolled in a first comparative study
      between Optopad and the Isihara tests. In a second comparative study, Optopad vs.
      the Farnworth-Munsell test (FM 100H), a total of 66 adult eyes were included.
      Besides the agreement between tests, the correlation between FM 100H and Optopad
      outcomes were investigated. Multiple regression analysis was used to predict the
      total error score (TES) from contrast thresholds measured with the Optopad test.
      RESULTS: The Ishihara and Optopad tests detected the same anomalous patients.
      Concerning FM 100H vs. Optopad, 10 subjects were diagnosed as anomalous with both
      tests, 3 mild anomalous cases based on TES were classified as normal with
      Optopad, and 2 anomalous subjects based on Optopad test showed normal TES values.
      Statistically significant correlations of TES and partial error red-green
      (PTESRG) with thresholds measured with the red-green Optopad stimuli were found.
      A multiple quadratic regression model was obtained relating TES and chromatic
      contrast values from Optopad (R2 = 0.855), with only 13 cases showing residuals
      of >= 25 units. CONCLUSIONS: The design and implementation of a chromatic
      contrast discrimination test has been carried out, with promising clinical
      results. This test seems to provide comparable outcomes to those obtained with
      Ishihara and FM 100H tests.

PMID- 30291437
TI  - The significance of tissue biopsy for fungi in necrotizing otitis externa.
AB  - INTRODUCTION: The conventional treatment for necrotizing otitis externa (NOE) is
      prolonged anti-pseudomonas therapy, with surgical treatment in non-responsive
      patients. The aim of the present study is to describe the course of management of
      patients with non-responsive NOE undergoing hyperbaric oxygen therapy (HBOT), and
      to investigate the importance of tissue biopsy for fungi in this group of
      patients. MATERIALS AND METHODS: A retrospective study conducted between January
      2010 and December 2013 at an Otolaryngology Head and Neck Surgery Department.
      Included were all 52 patients with NOE referred to our Medical Centre for further
      treatment including HBOT. RESULTS: Fifty-two consecutive patients, 29 men and 23
      women, with a mean age of 70.6 years, were included in our study. Twenty seven
      (51.9%) underwent surgical debridement. No significant difference was found
      between the group having surgical intervention, and those who did not, with
      regard to sex, age, comorbidities, cranial nerve involvement or laboratory
      results. However, those who had surgical intervention had a statistically
      significant higher rate of fungal infection (P = 0.049). After completing 7 weeks
      of HBOT, a significantly lower WBC count was observed in the fungus-infected
      group (7000 vs 7.800, P = 0.03), and a tendency towards lower CRP levels in the
      fungus-infected group (16 vs 58, P = 0.087). CONCLUSION: Patients with NOE should
      have a comprehensive surgical intervention when delayed healing is observed,
      because proper fungal culturing might change the course of treatment and improve
      prognosis. LEVEL OF EVIDENCE: 4.

PMID- 30291438
TI  - Non-monotonic accumulation of spike time variance during membrane potential
      oscillations.
AB  - A spike-phase neural code has been proposed as a mechanism to encode stimuli
      based on the precise timing of spikes relative to the phase of membrane potential
      oscillations. This form of coding has been reported in both in vivo and in vitro
      experiments across several regions of the brain, yet there are concerns that such
      precise timing may be compromised by an effect referred to as variance
      accumulation, wherein spike timing variance increases over the phase of an
      oscillation. Here, we provide a straightforward explanation of this effect based
      on the theoretical spike time variance. The proposed theory is consistent with
      recordings of mitral neurons. It shows that spike time variance can increase in a
      nonlinear fashion with spike number, in a way that is dependent upon the
      frequency and amplitude of the oscillation. Further, non-monotonic accumulation
      of variance can arise from different combinations of oscillation parameters.
      Nonlinear accumulation sometimes leads to lower variance than that of a mean rate
      matched homogeneous Poisson process, particularly for spikes that occur in later
      phases of oscillation. However, such an advantage is limited to a narrow range of
      oscillation amplitudes and frequencies. These results suggest fundamental
      constraints on spike-phase coding, and reveal how certain spikes in a sequence
      may exhibit increased firing time precision relative to their neighbors.

PMID- 30291439
TI  - Correction to: Amphi-enterobactin commonly produced among Vibrio campbellii and
      Vibrio harveyi strains can be taken up by a novel outer membrane protein FapA
      that also can transport canonical Fe(III)-enterobactin.
AB  - In the original publication, third author's name was incorrectly published as
      Aneta L. Jelowicki.

PMID- 30291440
TI  - Linked color imaging can enhance recognition of early gastric cancer by high
      color contrast to surrounding gastric intestinal metaplasia.
AB  - BACKGROUND: Linked color imaging (LCI) increases the visibility of early gastric
      cancers, which may be associated with characteristic findings including
      background purple mucosae. These lesions are found in areas of chronic gastritis
      and surrounding mucosa. The aim of this study is to objectively characterize
      these lesions by color differences and color component values using LCI. METHODS:
      Fifty-two patients with early gastric cancer were enrolled. Color differences
      were calculated prospectively in malignant lesions and adjacent mucosa and
      compared with histological findings in resected specimens. Color component values
      of L*, a*, and b* were compared between purple and non-purple mucosae in areas of
      chronic gastritis. Based on histological findings, the accuracy of identifying
      gastric intestinal metaplasia was calculated. RESULTS: Cancers and surrounding
      mucosa in 74% of lesions had similar colors using white light imaging (WLI),
      whereas purple mucosa surrounded part or all of cancers appearing orange-red,
      orange or orange-white using LCI. Greater color differences were seen using LCI
      compared to WLI, including flat-type cancers, leading to higher contrast. The
      surrounding purple mucosa corresponded histologically to intestinal metaplasia,
      facilitating the identification of malignant lesions. Forty lesions (83%) with
      purple mucosa and eight lesions (17%) with non-purple mucosa in areas of chronic
      gastritis were diagnosed as intestinal metaplasia by biopsy (83% accuracy). Color
      component values of purple mucosa differ significantly from those of non-purple
      mucosae. CONCLUSIONS: LCI images have higher color contrast between early gastric
      cancers and surrounding mucosa compared to WLI. A characteristic purple color
      around gastric cancers using LCI represents intestinal metaplasia.

PMID- 30291441
TI  - Impact of FAAH genetic variation on fronto-amygdala function during emotional
      processing.
AB  - Recent translational studies identified a common endocannabinoid polymorphism,
      FAAH C385A, in the gene for the fatty acid amide hydrolase (FAAH). This
      polymorphism alters endocannabinoid anandamide levels, which are known to be
      involved in the fronto-amygdala circuitry implicated in mood regulation and
      anxiety-like behaviors. While it has been shown that the variant that selectively
      enhances fronto-amygdala connectivity at rest is associated with decreased
      anxiety-like behaviors, no study so far has investigated whether this finding of
      FAAH-related differential plasticity extends to task-related differential
      functional expression and regulation during negative emotional processing. Using
      an imaging genetics approach, this study aimed to replicate and extend prior
      findings by examining functional activity and task-related connectivity in fronto
      amygdala regions during emotion reactivity and emotional down-regulation of
      negative affect. Therefore, 48 healthy young adults underwent a functional MRI
      resting state measurement, completed an emotion regulation paradigm and provided
      self-reports on anxiety and use of emotion regulation strategies. In line with
      previous studies, preliminary evidence suggests that A-allele carriers
      demonstrate stronger fronto-amygdala connectivity during rest. In addition,
      exploratory whole-brain analyses indicate differential functional activity of A
      allele carriers during emotion reactivity and emotion regulation. There were no
      associations with anxiety-related self-reports and use of emotional regulation
      strategies. Further research using larger samples and polygenic approaches is
      indicated to clarify the precise role and its underlying mechanisms in emotion
      processing.

PMID- 30291442
TI  - Asparagine alters action potential parameters in single plant cell.
AB  - Effect of amino acid L-asparagine on electrical signalling of single Nitellopsis
      obtusa (Characeaen) cell was investigated using glass-microelectrode technique in
      current-clamp and voltage-clamp modes. Cell exposure for 30 min to 0.1 mM and 1
      mM of asparagine resulted in changes of electrically stimulated action potential
      (AP) parameters in comparison to standard conditions. Results indicate that
      asparagine acts in dose-dependent manner: increases AP amplitude by
      hyperpolarizing AP threshold potential (Eth), prolongs action potential
      repolarization, increases maximum Cl- efflux amplitude along with the increase of
      activation and inactivation durations. Presented findings provide new aspects of
      exogenous amino acids' effect on plants' electrical signalling with emphasis on
      separate single plant cell excitability and AP characteristics.

PMID- 30291443
TI  - Evolution of light-independent protochlorophyllide oxidoreductase.
AB  - The nonhomologous enzymes, the light-independent protochlorophyllide reductase
      (DPOR) and the light-dependent protochlorophyllide oxidoreductase (LPOR),
      catalyze the reduction of protochlorophyllide (Pchlide) to chlorophyllide
      (Chlide) in the penultimate step of biosynthesis of chlorophyll (Chl) required
      for photosynthetic light absorption and energy conversion. The two enzymes differ
      with respect to the requirement of light for catalysis and oxygen sensitivity.
      DPOR and LPOR initially evolved in the ancestral prokaryotic genome perhaps at
      different times. DPOR originated in the anoxygenic environment of the Earth from
      nitrogenase-like enzyme of methanogenic archaea. Due to the transition from
      anoxygenic to oxygenic photosynthesis in the prokaryote, the DPOR was mostly
      inactivated in the daytime by photosynthetic O2 leading to the evolution of
      oxygen-insensitive LPOR that could function in the light. The primary
      endosymbiotic event transferred the DPOR and LPOR genes to the eukaryotic
      phototroph; the DPOR remained in the genome of the ancestor that turned into the
      plastid, whereas LPOR was transferred to the host nuclear genome. From an
      evolutionary point of view, several compelling theories that explain the
      disappearance of DPOR from several species cutting across different phyla are as
      follows: (i) pressure of the oxygenic environment; (ii) change in the light
      conditions and temperature; and (iii) lineage-specific gene losses, RNA editing,
      and nonsynonymous substitution. Certain primary amino acid sequence and the
      physiochemical properties of the ChlL subunit of DPOR have similarity with that
      of LPOR suggesting a convergence of these two enzymes in certain evolutionary
      event. The newly obtained sequence data from different phototrophs will further
      enhance the width of the phylogenetic information on DPOR.

PMID- 30291444
TI  - Surgical starting time in the morning versus the afternoon: propensity score
      matched analysis of operative outcomes following laparoscopic colectomy for
      colorectal cancer.
AB  - BACKGROUND: The number of colorectal cancer cases is increasing, and so the
      number of laparoscopic colectomy procedures being performed is also increasing,
      leading to an increased workload for surgeons. However, operating for prolonged
      time periods may cause surgeons to lose their concentration and develop fatigue.
      We hypothesized that there is a time-of-day variation in outcome for patients
      with colorectal cancer who undergo laparoscopic colectomy. The present study
      aimed to compare the operative outcome between laparoscopic colectomy for
      colorectal cancer performed in the morning versus the afternoon. METHODS: This
      was a single-center, retrospective study. All 1961 consecutive patients who
      underwent laparoscopic surgery for colorectal cancer between 2007 and 2017 were
      included; 1006 of these patients underwent morning surgery, while 955 underwent
      afternoon surgery. These patients were analyzed using propensity score matching,
      giving 791 patients in each group. The short- and long-term outcomes in both
      groups were compared. RESULTS: Before propensity score matching, the morning
      group had a larger mean tumor size than the afternoon group (30 cm vs 35 cm; P =
      0.0035). After matching, the two groups did not significantly differ in any
      patient characteristics. Compared with the afternoon group, the morning group had
      a significantly lesser incidence of intra-operative organ injury (0.25% vs 1.13%;
      P = 0.027), and a significantly greater incidence of post-operative abdominal
      abscess (2.03% vs 0.75% P = 0.028). The incidences of other complications and
      morbidities were similar in both groups. The median operative time in the morning
      group (201 min) was significantly longer than that in the afternoon group (193
      min; P = 0.0124). The two groups did not differ in 5-year overall survival rates
      and 5-year disease-free rates within any disease stage. CONCLUSIONS: Surgical
      start times are correlated with surgical outcomes. Our data will help to ensure
      the safest possible surgeries.

PMID- 30291445
TI  - The frequency and diagnostic accuracy of hand deformities in Parkinson's disease.
AB  - Hand deformities are well-known abnormalities observed in patients with
      Parkinson's disease (PD). We determined the frequency and diagnostic accuracy of
      hand deformities in PD. We studied 44 consecutive patients with PD, 44 age- and
      gender-matched normal controls and 22 patients with essential tremor (ET). By
      means of photographs taken in both hands of all participants, the degree of
      metacarpophalangeal (MCP) joint flexion was quantified by software and by blinded
      evaluations using a semiquantitative scale from the radial aspect, we grouped
      hands into four grades. The presence of classical striatal hand deformity (CSHD),
      defined as MCP joint flexion, proximal interphalangeal joint extension and distal
      interphalangeal joint flexion was also evaluated. Patients with PD had a higher
      frequency of MCP joint flexion and CSHD compared to normal controls and patients
      with ET. Mean MCP joint flexion was higher in both hands in patients with PD:
      20.8 degrees  vs. normal controls (3.3 degrees -3.9 degrees ) and patients with
      ET (2.8 degrees -6.3 degrees ), P = 0.001. Concordance between evaluators for MCP
      joint flexion was fair: kappa = 0.34 (P < 0.001), but poor for CSHD: kappa =
      0.142-0.235 (P < 0.05). A right hand MCP joint flexion of 12.5 degrees  and left
      hand of 10.5 degrees , showed similar sensitivity (0.70) and specificity (between
      0.75 and 0.80) than any degree of MCP joint flexion for the diagnosis of PD. CSHD
      had a sensitivity (0.60-0.80) and specificity (0.78-0.98) for the diagnosis of
      PD. Hand deformities are commonly observed in patients with PD, they may aid in
      the diagnosis of PD when compared to normal controls and patients with ET.

PMID- 30291446
TI  - Zintl superalkalis as building blocks of supersalts.
AB  - Alkali metal cations and halogen anions are common components of ionic salts.
      Recently, a new class of salts termed supersalts was reported, each of which
      contains a superalkali and a superhalogen that mimic an alkali metal cation and a
      halogen anion, respectively. Using three different functionals, namely B3LYP,
      wB97X, and M06-2X, we theoretically investigated a new subset of supersalts
      composed of Zintl-based superalkalis and inorganic superhalogens via
      computational modeling. The calculated dipole moment and first-order
      hyperpolarizability values for these supersalts indicate that they present
      nonlinear optical (NLO) behavior. The supersalts of Zintl superalkalis (Ca2P7,
      Sr2P7, Ba2P7) and superhalogens (BF4, BeF3, NO3) studied here were found to be
      stable. Graphical Abstract Using the first-principles calculation, a new class of
      supersalts by using Zintl-based superalkalis and inorganic superhalogens has been
      designed.

PMID- 30291448
TI  - Microbiota disruption leads to reduced cold tolerance in Drosophila flies.
AB  - It is now acknowledged that bacteria from gut microbiota deeply interact with
      their host by altering many physiological traits. Such interplay is likely to
      consequently affect stress tolerance. Here, we compared cold and heat tolerance
      of Drosophila melanogaster flies with undisrupted (control (Co)) versus disrupted
      gut microbiota (dechorionated eggs (De)). The disrupting treatment strongly
      reduced bacterial load in flies' guts, though 16S sequencing analysis did not
      evidence strong diversity changes in the remaining bacterial community. Both
      chill coma recovery and acute cold survival were repeatedly lower in De than in
      Co flies under our experimental conditions. However, heat tolerance was not
      consistently affected by gut disruption. Our results suggest that microbiota
      related effects on the host can alter ecologically relevant traits such as
      thermal tolerance.

PMID- 30291447
TI  - A salamander's toxic arsenal: review of skin poison diversity and function in
      true salamanders, genus Salamandra.
AB  - Terrestrial salamanders of the genus Salamandra represent one of the most
      prominent groups of amphibians. They are mainly distributed across Europe but
      also reach Northern Africa and the Near East. Members of the six currently
      accepted species have long been known to be poisonous; however, work on their
      toxins was mostly published in German language, and therefore, many nuances of
      these studies have remained hidden from the majority of herpetologists and
      toxinologists. Several Salamandra species are called fire salamanders due to
      their highly contrasted, black-yellow colouration which probably serves to deter
      predators, although thorough evidence for aposematism in Salamandra is still
      lacking. Salamandra skin toxins do not only represent a potent antipredator
      defence but may also have antimicrobial effects. A better understanding of this
      dual function of Salamandra skin secretions is of utmost importance in the face
      of the emergence of a fungal disease causing catastrophic declines of fire
      salamanders in Central Europe, caused by the fungus Batrachochytrium
      salamandrivorans. In this review, we summarize the knowledge on Salamandra
      toxins, providing a list of the compounds so far isolated from their secretion
      and focusing on the bioactivity of the major compounds in Salamandra secretions,
      the steroidal alkaloids. We identify priorities for future research, including a
      screening of co-occurrence of steroidal alkaloids and tetrodotoxins in
      salamandrids, chemical characterization of already identified novel steroidal
      compounds, elucidation of the presence and role of peptides and proteins in the
      secretion, and experimental in vitro and in vivo study of the interactions
      between bioactive compounds in Salamandra skin secretions and cutaneous fungal
      and bacterial pathogens.

PMID- 30291449
TI  - The first Gondwanan borioteiioid lizard and the mid-Cretaceous dispersal event
      between North America and Africa.
AB  - Borioteiioidea are an enigmatic group of Cretaceous lizards widely distributed in
      northern continents (Laurasia). Here, we describe the first borioteiioid lizard
      from Gondwana, represented by a new species of the polyglyphanodontine genus
      Bicuspidon, B. hogreli sp. nov., from the Cenomanian Kem Kem beds of Morocco. The
      discovery of Bicuspidon hogreli sp. nov., which is one of the oldest known member
      of Polyglyphanodontini, challenges previous assumptions on the center of origin
      and dispersal of the group. In addition, the known distribution of Bicuspidon
      (Cenomanian of Utah and Morocco, and Santonian-Maastrichtian of eastern Europe)
      suggests a complex palaeobiogeographical history for the genus. The existence of
      a terrestrial dispersal route persisting during the whole Early Cretaceous
      between North America and Africa is hypothesized to explain some similarities
      observed between the Cenomanian squamate assemblages of these two continents.
      Alternatively, dispersal between the two landmasses may have occurred by
      transatlantic rafting. During the Cenomanian-Santonian interval, Bicuspidon
      colonized the European archipelago probably from North Africa, like many
      "Eurogondwanan" taxa.

PMID- 30291450
TI  - Long noncoding RNA and gene expression analysis of melatonin-exposed Liaoning
      cashmere goat fibroblasts indicating cashmere growth.
AB  - Cashmere produced from Liaoning cashmere goat is highly valuable. Melatonin is an
      important factor affecting cashmere growth and can regulate the growth cycle via
      effects on gene expression. Long noncoding RNAs (lncRNAs) regulate gene
      expression, but detailed studies of their effect on hair growth are lacking. To
      explore how lncRNA mediates the effects of melatonin on cashmere growth, we used
      RNA-Seq including a control condition (C) and three melatonin treatments (1.0 g/L
      24 h (M1_24H), 0.2 g/L 24 h (M2_24H), 0.2 g/L 72 h (M2_72H)). M1_24H, M2_24H, and
      M2_72H had 32, 10, and 113 differentially expressed lncRNAs, respectively. Gene
      ontology (GO) and pathway analyses results showed that melatonin was most
      beneficial to cashmere growth at 0.2 g/L 72 h, and nuclear factor (NF)-kappaB
      signaling corresponding to an effect of LncRNA MTC was involved in hair follicle
      development. We found that melatonin upregulated XLOC_005914 lncRNA (LncRNA MTC).
      Proliferation increased in the 0.2 g/L 72 h condition and cells with high LncRNA
      MTC expression, but it was reduced in fibroblasts with knocked down LncRNA MTC
      expression. This is the first report that LncRNA MTC promotes fibroblast
      proliferation and regulates hair follicle development and cashmere growth by
      activating NF-kappaB signaling.

PMID- 30291451
TI  - Spondyloarthropathy in vertebrae of the aquatic Cretaceous snake Lunaophis
      aquaticus, and its first recognition in modern snakes.
AB  - Inflammatory arthritis is documented for the first time in snakes. Ossification
      of the intervertebral capsule and zygapophyseal joints resulting in segmental
      vertebral fusion was observed in the aquatic Cretaceous snake Lunaophis
      aquaticus. Such pathologic alterations are pathognomonic for the
      spondyloarthropathy form of inflammatory arthritis. A survey of 2144 snakes in
      recent collections, performed to identify Holocene prevalence, revealed only two
      occurrences in extant snakes. The findings in Bitis gabonica and Elaphe taeniura
      were indistinguishable from those noted in Lunaophis aquaticus and identical to
      those previously recognized in modern varanids. The pathology likely represents a
      form of reactive arthritis related to enteropathic infection. While the disease
      probably did not affect general locomotion, its vertebral column position may
      have compromised mating.

PMID- 30291452
TI  - Snort acoustic structure codes for positive emotions in horses.
AB  - While the vocal coding of human and animal internal states has been widely
      studied, the possible acoustic expression of "positive" emotions remains poorly
      known. Recent studies suggest that snorts (non-vocal sounds produced by the air
      expiration through the nostrils) appear to be reliable indicators of positive
      internal states in several ungulate species. Here, we hypothesised in horses that
      the acoustic structure of the snort could vary with the subjects' current
      emotional state. Indeed, a preliminary sound analysis of snorts let us suggest
      structure variations related to the presence of pulsations. We recorded snorts
      from 20 horses living in a riding center. Auditory playbacks run with 20 humans
      first confirmed the existence of two snort subtypes, i.e. one pulsed and one non
      pulsed. Observations were then conducted to compare the distribution of these two
      subtypes according to the location (stall/pasture) of the signaller as a
      contextual determinant of its internal state and to its ears' position as a
      reflection of its emotional state. We found that both subtypes were
      preferentially observed in positive contexts, but that pulsed snorts were even
      more associated with highly appreciated situations (in pasture and with ears
      forward). This study is a step further in the identification of indicators of
      positive emotions in horses and more generally in the understanding of the
      acoustic emotions' coding.

PMID- 30291453
TI  - Enzymatic determination of uric acid using water-soluble CuInS/ZnS quantum dots
      as a fluorescent probe.
AB  - Glutathione-capped water-soluble CuInS/ZnS quantum dots (QDs) were prepared by a
      microwave-assisted method. Their fluorescence, with excitation/emission peaks at
      380/570 nm, is found to be quenched by hydrogen peroxide (H2O2) that is produced
      by the uricase catalyzed oxidation of uric acid (UA) and oxygen. The findings are
      used in a quenchometric method for the determination of UA. The effects of
      different ligands on the QDs, of pH value, buffers, enzyme ratio and reaction
      time were optimized. The detection limit for UA is 50 nM which is lower than
      other QD-based method, and the detection ranges extends from 0.25-4.0 MUM. The
      assay is simple and sensitive, and no further modification of the QDs is
      required. Graphical abstract ?.

PMID- 30291456
TI  - Impact of environmental temperatures on mortality, sex and caste ratios in
      Melipona interrupta Latreille (Hymenoptera, Apidae).
AB  - Temperature is a major driver of biological phenomena, from metabolism to
      ecological interactions and rates of evolutionary diversification. However,
      species vary greatly in their thermal tolerance, as well as the temperature under
      which they perform best. This study aimed to investigate the effect of
      experimental manipulation of environmental temperatures on the individual
      mortality and phenotypic composition of colonies of Melipona interrupta. To
      fulfill these objectives, 30 colonies in equivalent developmental conditions were
      artificially subjected to different temperatures. Temperatures were monitored by
      thermo-hygrometers, and immature mortality and sex and caste ratios were observed
      in brood combs during 14 months. A strong effect of external temperature on
      immatures was detected on deviations from 28 to 30  degrees C (the natural
      average temperature inside the colony), causing an increase in mortality.
      Likewise, a significant effect of temperature on sex ratio was detected, with
      male:female ratio decreasing at temperatures below and above 28-30  degrees C.
      Lastly, there was no clear evidence for an effect of temperature on caste ratio,
      although queens appeared to become relatively more frequent at warmer
      temperatures. The results of this study allow us to conclude that anthropogenic
      changes, whose effect can be extrapolated to the similar natural changes, that
      modify the environmental temperatures to which M. interrupta colonies are exposed
      are likely to compromise their survival, mainly through individual mortality.

PMID- 30291455
TI  - Meta-networks for the study of biogeographical traits in ecological networks: the
      Mexican hummingbird-plant assemblage.
AB  - Recent studies on ecological networks have quantified the contribution of
      ecological, historical, and evolutionary factors on the structure of local
      communities of interacting species. However, the influence of species'
      biogeographical traits, such as migratory habits or phylogeographical history, on
      ecological networks is poorly understood. Meta-networks, i.e., networks that
      cover large spatial extensions and include species not co-occurring locally,
      enable us to investigate mechanisms that operate at larger spatial scales such as
      migratory patterns or phylogeographical distributions, as well as indirect
      relationships among species through shared partners. Using a meta-network of
      hummingbird-plant interaction across Mexico, we illustrate the usefulness of this
      approach by investigating (1) how biogeographical and morphological factors
      associate with observed interactions and (2) how species-specific biogeographical
      characteristics associate with species' network roles. Our results show that all
      studied hummingbird and plant species in the meta-network were interrelated,
      either directly or through shared partners. The meta-network was structured into
      modules, resulting from hummingbirds and plants interacting preferentially with
      subsets of species, which differed in biogeographical, and, to a lesser extent,
      morphological traits. Furthermore, migrants and hummingbirds from Nearctic,
      Transition, and widespread regions had a higher topological importance in the
      meta-network. Our study illustrates how meta-networks may contribute to our
      current knowledge on species' biogeographical traits and biotic interactions,
      providing a perspective complementary to local-scale networks.

PMID- 30291454
TI  - Seasonal changes in eicosanoid metabolism in the brown bear.
AB  - Polyunsaturated fatty acids (PUFAs) exert several important functions across
      organ systems. During winter, hibernators divert PUFAs from oxidation, retaining
      them in their tissues and membranes, to ensure proper body functions at low body
      temperature. PUFAs are also precursors of eicosanoids with pro- and anti
      inflammatory properties. This study investigated seasonal changes in eicosanoid
      metabolism of free-ranging brown bears (Ursus arctos). By using a lipidomic
      approach, we assessed (1) levels of specific omega-3 and omega-6 fatty acids
      involved in the eicosanoid cascade and (2) concentrations of eicosanoids in
      skeletal muscle and blood plasma of winter hibernating and summer active bears.
      We observed significant seasonal changes in the specific omega-3 and omega-6
      precursors. We also found significant seasonal alterations of eicosanoid levels
      in both tissues. Concentrations of pro-inflammatory eicosanoids, such as
      thromboxane B2, 5-hydroxyeicosatetraenoic acid (HETE), and 15-HETE and 18-HETE,
      were significantly lower in muscle and/or plasma of hibernating bears compared to
      summer-active animals. Further, plasma and muscle levels of 5,6
      epoxyeicosatrienoic acid (EET), as well as muscle concentration of 8,9-EET,
      tended to be lower in bears during winter hibernation vs. summer. We also found
      lower plasma levels of anti-inflammatory eicosanoids, such as 15dPGJ2 and PGE3,
      in bears during winter hibernation. Despite of the limited changes in omega-3 and
      omega-6 precursors, plasma and muscle concentrations of the products of all
      pathways decreased significantly, or remained unchanged, independent of their pro
      or anti-inflammatory properties. These findings suggest that hibernation in
      bears is associated with a depressed state of the eicosanoid cascade.

PMID- 30291457
TI  - Agriculture Occupational Exposures and Factors Affecting Health Effects.
AB  - PURPOSE OF REVIEW: Agriculture environments contain a variety of inflammatory
      aerosols that may increase risk for lung inflammation and disease in exposed
      individuals. In addition, epidemiological studies have also identified protective
      effects of rural environments and farming exposures. RECENT FINDINGS: In this
      review, we will discuss recent literature published since 2016 that investigates
      the impact of differing agricultural exposures on respiratory health. Discussions
      include the impact of farming modernization, education, and personal protective
      equipment usage among workers, timing and duration in mediating lung health
      outcomes, and population studies investigating the association between exposure
      and risk for numerous lung diseases.

PMID- 30291458
TI  - Photoelectrochemical determination of the activity of M.SssI methyltransferase,
      and a method for inhibitor screening.
AB  - A photoelectrochemical (PEC) method is described for the determination of the
      activity of M.SssI methyltransferase (MTase). The assay relies on enzyme-linkage
      reactions and a DNA intercalator Ru(bpy)2(dppz)2+ (where bpy is 2,2'-bipyridine,
      and dppz is dipyrido[3,2-a:2',3'-c]phenazine) which both serves as a PEC signal.
      The PEC electrode was obtained by immobilizing 5'-amino modified DNA strands
      (containing the methylation recognition site 5'-CCGG-3') on a polyethylenimine
      (PEI) coated ITO/SnO2 electrode with glutaraldehyde as crosslinking agent. In the
      presence of MTase and S-adenosyl-L-methionine, the 5'-CCGG-3' sequence in the DNA
      on the electrode is methylated. This protects the DNA strands from the shear of
      the methylation-sensitive restriction endonuclease HpaII. Consequently, more
      intact DNA strands remain on the surface of the electrode, providing more sites
      for Ru(bpy)2(dppz)2+ binding which in turn results in a high PEC response. The
      result demonstrates that the photocurrent increases linearly with the activity of
      MTase from 5 to 80 U.mL-1, and the limit of detection is 0.45 U.mL-1. The other
      MTases does not enhance the photocurrent, suggesting good selectivity of the
      assay. The method was also applied to rapid evaluate and screen the inhibitors of
      MTase. This strategy can be utilized to determinate the activity of other DNA
      MTases with specific DNA sequence. Graphical abstract Schematic presentation of a
      photoelectrochemical assay based on enzyme-linkage reactions and a photo
      electrochemical probe combined with the oxalic acid involved cyclic amplification
      system for the determination of methyltransferase activity.

PMID- 30291459
TI  - A test strip for ochratoxin A based on the use of aptamer-modified fluorescence
      upconversion nanoparticles.
AB  - An aptamer-based test strip is described for visual and instrumental
      determination of the mycotoxin ochratoxin A (OTA). It is based on the use of
      NaYF4:Yb,Er upconversion nanoparticles (UCNPs) as a label for the aptamer and on
      the competition between OTA and its complementary sequence for an OTA-specific
      aptamer. To improve the analytical performance, the optical properties of the
      UCNPs, the fluidity of the UCNP-aptamer conjugate, and the migration rate on the
      nitrocellulose membranes were investigated. Under the optimal experimental
      conditions and by using a 980-nm laser, the relative fluorescence intensity (test
      line value/control line value) is proportional to the logarithm of the OTA
      concentration over a range from 5 to 100 ng.mL-1 (R2 = 0.9955). The limit of the
      detection is 1.86 ng.mL-1. This aptamer based flow assay can be performed within
      15 min and has no serious cross-sensitivity to potentially interfering species.
      It was successfully applied to the determination of OTA in spiked wheat and beer
      samples. Graphical abstract An aptamer-based upconversion fluorescent strip based
      on the use of NaYF4:Yb,Er nanoparticles was developed for sensitive detection of
      Ochratoxin A. The limit of the detection was determined as 1.86 ng.mL-1. The
      assay can be performed within 15 min, indicating its great potential in point-of
      care testing.

PMID- 30291460
TI  - Silicon membrane filter designed by fluid dynamics simulation and near-field
      stress analysis for selective cell enrichment.
AB  - Selective cell enrichment technologies can play an important role in both
      diagnostic and therapeutic areas. However, currently used cell sorting techniques
      have difficulties in rapidly isolating only the desired target cells from a large
      volume of body fluids. In this work, we developed a filtering system that can
      quickly separate and highly concentrate cells from a large volume of solution,
      depending on their size, using a silicon membrane filter. To overcome the
      problems caused by material limitations of the brittle silicon, we designed a
      novel membrane filter with various pore designs. From these designs, the most
      optimal design with high pore density, while preventing crack formation was
      derived by applying fluid dynamics simulation and near-field stress analysis. The
      membrane filter system using the selected design was fabricated, and cell
      filtration performance was evaluated. The LNCaP cell in horse blood was recovered
      up to 86% and enriched to 187-fold compared to initial cell populations after
      filtration at a flow rate of 5 mL/min. The results demonstrate that the filter
      presented in this study can rapidly and selectively isolate target cells from a
      large volume of body fluid sample.

PMID- 30291461
TI  - RANKL-induced c-Src activation contributes to conventional anti-cancer drug
      resistance and dasatinib overcomes this resistance in RANK-expressing multiple
      myeloma cells.
AB  - The survival and growth of multiple myeloma (MM) cells are facilitated by cell
      cell interactions with bone marrow stromal cells and the bone marrow
      microenvironment. These interactions induce de novo drug resistance known as cell
      adhesion-mediated drug resistance. Our previous results recently revealed that
      the receptor activator of NF-kappaB (RANK) ligand (RANKL), which is expressed by
      bone marrow stromal cells, contributes to anti-cancer drug resistance through the
      activation of various signaling molecules and suppression of Bim expression in
      RANK-expressing MM cells. However, the detailed mechanisms underlying RANKL
      induced drug resistance remain uncharacterized. In the present study, we
      investigated the mechanism of RANKL-induced drug resistance in RANK-expressing MM
      cell lines. We found treatment of MM cells with RANKL-induced c-Src
      phosphorylation and activation of the downstream signaling molecules Akt, mTOR,
      STAT3, JNK, and NF-kappaB. In addition, treatment with dasatinib, a c-Src
      inhibitor, overcame RANKL- and bone marrow stromal cell-induced drug resistance
      to adriamycin, vincristine, dexamethasone, and melphalan by suppressing c-Src,
      Akt, mTOR, STAT3, JNK, and NF-kappaB activation and enhancing expression of Bim.
      Overall, RANKL- and bone marrow stromal cell-induced drug resistance correlated
      with the activation of c-Src signaling pathways, which caused a decrease in Bim
      expression. Dasatinib treatment of RANK-expressing MM cells re-sensitized them to
      anti-cancer drugs. Therefore, inhibition of c-Src may be a new therapeutic
      approach for overcoming RANKL-induced drug resistance in patients with MM.

PMID- 30291462
TI  - Identification and fine mapping of Bph33, a new brown planthopper resistance gene
      in rice (Oryza sativa L.).
AB  - BACKGROUND: Host-plant resistance is the most desirable and economic way to
      overcome BPH damage to rice. As single-gene resistance is easily lost due to the
      evolution of new BPH biotypes, it is urgent to explore and identify new BPH
      resistance genes. RESULTS: In this study, using F2:3 populations and near
      isogenic lines (NILs) derived from crosses between two BPH-resistant Sri Lankan
      rice cultivars (KOLAYAL and POLIYAL) and a BPH-susceptible cultivar 9311, a new
      resistance gene Bph33 was fine mapped to a 60-kb region ranging 0.91-0.97 Mb on
      the short arm of chromosome 4 (4S), which was at least 4 Mb distant from those
      genes/QTLs (Bph12, Bph15, Bph3, Bph20, QBph4 and QBph4.2) reported before. Seven
      genes were predicted in this region. Based on sequence and expression analyses, a
      Leucine Rich Repeat (LRR) family gene (LOC_Os04g02520) was identified as the most
      possible candidate of Bph33. The gene exhibited continuous and stable resistance
      from seedling stage to tillering stage, showing both antixenosis and antibiosis
      effects on BPH. CONCLUSION: The results of this study will facilitate map-based
      cloning and marker-assisted selection of the gene.

PMID- 30291464
TI  - Photobiomodulation on critical bone defects of rat calvaria: a systematic review.
AB  - Bone defects following trauma represent a high impact on the quality of life of
      millions of people around the world. The aim of this study was to review
      photobiomodulation (PBM) action in the treatment of bone critical defects in rat
      calvaria, related to evaluation of the current protocols applied. One hundred and
      forty-seven articles related to the subject were found by searching the main
      databases (Pubmed, Lilacs, Web of Science, and Scopus) considering the period of
      publication until the year 2017, and only 14 corresponded the inclusion criteria
      established for this systematic review. The main parameters of the PBM were
      expressed in Table 1. In addition, it was possible to observe the use of two
      different wavelengths (red and infrared), which are considered therapeutic. Most
      of the evaluated articles presented positive results that describe a greater
      amount of neoformed bone, an increase in collagen synthesis, and a contribution
      to microvascular reestablishment. However, two studies report no effect on the
      repair process when the PBM was used. In addition, we observed considerable
      variations between the values of power, fluence, and total energy, which make it
      difficult to compare the results presented between the selected studies. It was
      possible to conclude that the infrared laser was more effective in positively
      stimulating the bone repair process of critical defects. Furthermore, a
      discrepancy was found in the parameter values used, which made it difficult to
      choose the best protocol for the treatment of this type of lesion.

PMID- 30291465
TI  - Effectiveness of photopolymerization in composite resins using a novel 445-nm
      diode laser in comparison to LED and halogen bulb technology.
AB  - Challenges especially in the minimal invasive restorative treatment of teeth
      require further developments of composite polymerization techniques. These
      include, among others, the securing of a complete polymerization with moderate
      thermal stress for the pulp. The aim of this study is to compare current light
      curing sources with a blue diode laser regarding curing depth and heat generation
      during the polymerization process. A diode laser (445 nm), a LED, and a halogen
      lamp were used for polymerizing composite resins. The curing depth was determined
      according to the norm ISO 4049. Laser output powers of 0.1, 0.5, 1, and 2 W were
      chosen. The laser beam diameter was adapted to the glass rod of the LED and the
      halogen lamp (8 mm). The irradiation time was fixed at 40 s. To ascertain DeltaT
      values, the surface and ground area temperatures of the cavities were
      simultaneously determined during the curing via a thermography camera and a
      thermocouple. The curing depths for the LED (3.3 mm), halogen lamp (3.1 mm) and
      laser(0.5/1 W) (3/3.3 mm) showed no significant differences (p < 0.05). The
      values of DeltaTsurface as well as DeltaTground also showed no significant
      differences among LED, halogen lamp, and laser(1 W). The DeltaTsurface values
      were 4.1LED, 4.3halogen lamp, and 4.5  degrees C for the laser while the
      DeltaTground values were 2.7LED, 2.6halogen lamp, and 2.9  degrees C for the
      laser. The results indicate that the blue diode laser (445 nm) is a feasible
      alternative for photopolymerization of complex composite resin restorations in
      dentistry by the use of selected laser parameters.

PMID- 30291463
TI  - The Multifaceted B Cell Response in Allergen Immunotherapy.
AB  - While allergen immunotherapy (AIT) for IgE-mediated diseases holds curative
      potential, the considerable heterogeneity in clinical outcomes may relate to the
      complex mechanisms of tolerance. The regulation of humoral immunity by AIT
      contributes to the suppression of allergic responses. Recent findings have
      revealed novel roles for IgA and IgG antibodies in the induction of tolerance.
      These mechanisms synergize with their ability to block allergen-IgE binding and
      mediate inhibitory signaling of effector cells of the allergic response. In
      addition, the regulatory activity of B cells in AIT extends beyond IL-10
      secretion and induction of IgG4. Here, we review the evolution of the B cell
      response during AIT with special emphasis on the novel protective mechanisms
      entailing humoral immunity.

PMID- 30291466
TI  - The downside of antimicrobial agents for wound healing.
AB  - The use of topical antimicrobials is beneficial for infection control in wound
      care because wound infection is the major cause of delayed healing. The
      advantages of topical over systemic antimicrobials include a higher concentration
      at the target site, fewer systemic adverse effects, and a lower incidence of
      antimicrobial resistance. Nowadays, topical antimicrobials are divided into three
      groups: disinfectants, antiseptics, and antibiotics. Only antiseptics and
      antibiotics can be applied to living skin; therefore, this review will focus only
      on these groups. The advantages of each topical antimicrobial are well
      established; however, their disadvantages remain prominent. It is widely known
      that antiseptics show higher cytotoxicity and a broader spectrum of activity than
      antibiotics, whereas antibiotics show a higher probability of bacterial
      resistance development. However, there are still many adverse effects, resulting
      from each topical antimicrobial. This review aims to summarize the possible
      adverse effects of commonly used antiseptics (biguanide, silver, iodine, chlorine
      compounds, and other antiseptics), antibiotics (bacitracin, mafenide, mupirocin,
      neomycin, and silver sulfadiazine), and natural antimicrobials (curcumin and
      honey). Moreover, the antimicrobials that should be avoided in particular
      populations are also summarized in this review in order to increase awareness for
      antimicrobial selection in those populations.

PMID- 30291467
TI  - Self-assessment reliability in multiple sclerosis: the role of socio-demographic,
      clinical, and quality of life aspects.
AB  - INTRODUCTION: Several multiple sclerosis studies matching self- and physician
      assessment of disease course and disability show moderate and high agreement
      respectively. However, the role played by socio-demographic, clinical, and
      quality of life (QoL) factors was not much investigated. The study aims at
      exploring how self-/physician agreement could depend on these variables.
      MATERIALS AND METHODS: Participants were asked to report own disease course and
      disability according to preset categories. Kappa-value and confidence interval
      (CI) for disease course and two-way random interclass correlation coefficient
      (ICC) and CI for disability were calculated to evaluate self-/physician
      agreement. Chi2 was applied to examine whether other factors (gender, age,
      education, civil status, disease duration, fatigue, quality of life) had
      systematic effects. RESULTS: Data analysis on 203 participants indicated fair
      agreement (Kappa-value = 0.30; 95% CI 0.23-0.38) and no dependency on the
      categories of each variable for disease course. Satisfactory correlation was
      found for disability (ICC = 0.74; 95% IC 0.67-0.80), good agreement was found for
      almost all variable categories, and significant differences were observed for
      education (better agreement for higher levels), disease duration, fatigue and QoL
      (better agreement for worse conditions). DISCUSSION: Results seem to suggest that
      higher education and worse clinical and QoL conditions could engage the patient
      in developing more disease awareness and realistic self-perception and self
      evaluation.

PMID- 30291468
TI  - Japan Society of Gynecologic Oncology guidelines 2017 for the treatment of
      uterine cervical cancer.
AB  - The Japan Society of Gynecologic Oncology (JSGO) Guidelines 2017 for the
      Treatment of Uterine Cervical Cancer are for the purpose of providing standard
      treatment strategies for cervical cancer, indicating treatment methods currently
      considered appropriate for cervical cancer, minimizing variances in treatment
      methods among institutions, improving the safety of treatment and prognosis of
      diseases, reducing the economic and psychosomatic burden of patients by promoting
      performance of appropriate treatment, and enhancing mutual understanding between
      patients and healthcare professionals. The guidelines were prepared through
      consensus of the JSGO Guideline Committee, based on careful review of evidence
      gathered through the literature searches and in view of the medical health
      insurance system and actual clinical practice situations in Japan. The guidelines
      comprise eight chapters and five algorithms. The main features of the 2017
      revision are as follows: (1) evidence was collected using a search formula and
      with cooperation of the Japan Library Association. The bibliographical search
      formula was placed at the end of the book; (2) regarding clinical questions (CQs)
      where evidence or clinical inspection in Japan was lacking, opinions of the
      Guidelines Committee were described as "proposals for future directions"; (3)
      cervical intraepithelial neoplasia (CIN) 3 and adenocarcinoma in situ (AIS) were
      treated as a cervical precancerous lesion; (4) the CQs of endoscopic surgery,
      radical trachelectomy, and sentinel node biopsy were newly added in Chapter 3,
      "primary treatment for stage IB-II cervical cancer"; and (5) the CQ about hormone
      replacement therapy after cancer treatment was newly established. Each
      recommendation is accompanied by a classification of recommendation categories
      based on the consensus reached by the Guideline Committee members. Here, we
      present the English version of the JSGO Guidelines 2017 for the Treatment of
      Uterine Cervical Cancer.

PMID- 30291469
TI  - Venovenous extracorporeal membrane oxygenation for the management of critical
      airway stenosis.
AB  - Venovenous extracorporeal membrane oxygenation (VV-ECMO) is used not only support
      gas transfer of patients suffering from respiratory failure, but also to manage
      hypoxic patients with critical airway obstruction during various procedures. We
      present a case in which we electively used VV-ECMO to facilitate tube placement
      and tracheal biopsy in a 67-year-old female with critical tracheal stenosis. The
      patient was transferred to our hospital for a surgical treatment after emergent
      tracheostomy for postoperative management of cerebral hemorrhage in right
      putamen. Her trachea was severely stenotic and just enough for a 5.5 mm
      tracheostomy tube. Removal of tracheostomy tube, tracheal wall biopsy and intra
      tracheal tube placement were successfully performed under VV-ECMO support,
      drainage from inferior vena cava returned into the right ventricle (RV). RV
      perfusion was a very useful and effective method in VV-ECMO system, although some
      careful wire management was needed under fluoroscopic guidance.

PMID- 30291471
TI  - [Effects of examinations on learning and the curriculum: A position from
      Switzerland].
AB  - The federal law for higher academic medical professions (MedBG) constitutes a
      program accreditation as well as a federal licensing exam in medicine; both
      instruments influence the curricula and their further development.Parallel to the
      Bologna reform in Switzerland for all university degrees the federal licensing
      exam in medicine has been revised. The swiss catalogue of learning objectives
      (SCLO, 2nd edition 2008) served as mandatory content reference for the exam and
      initiated numerous curricular developments. The new federal licencing exam has
      been implemented in 2011 comprising a MCQ-Part and a structured clinical
      practical exam in the OSCE format. Particularly this exam triggered the
      introduction of OSCEs in Zurich as well as in other Swiss universities.The latest
      national initiative to increase the number of medical students and the
      introduction of the new edition of the catalogue of learning objectives in 2017
      will have relevant effects on curricular developments in Switzerland.

PMID- 30291470
TI  - Dickkopf-1 (Dkk-1) serum levels in systemic sclerosis and rheumatoid arthritis
      patients: correlation with the Trabecular Bone Score (TBS).
AB  - The aim of this research was to determine any correlations between Dickkopf-1
      serum levels (Dkk-1, a natural inhibitor of the Wnt signaling pathway promoting
      osteoclastogenesis) and the Trabecular Bone Score (TBS), in systemic sclerosis
      (SSc) and rheumatoid arthritis (RA) patients. It also aimed at determining any
      difference in Dkk-1 serum levels between SSc and RA patients and a control group
      (CNT) of healthy subjects. A prospective study was carried out in 60 SSc and 60
      RA patients and 60 CNT. Dkk-1 serum levels were evaluated by the ELISA method
      (Quantikine Human Dkk-1 Immunoassay, R&D System, Minneapolis, USA). The severity
      of microvascular damage was evaluated by nailfold videocapillaroscopy (NVC
      patterns: "Early," "Active," "Late"), in the SSc patients. TBS analysis and bone
      mineral density (BMD, g/cm2) were measured in all patients/subjects. The SSc
      patients showed higher Dkk-1 serum levels than RA (p < 0.004) and CNT (p <
      0.0001) patients. SSc patients, showing the "Late" NVC pattern had statistically
      higher Dkk-1 serum levels than patients with either the "Active" or "Early" (p <
      0.004) patterns. Only in the "Late" NVC pattern group of SSc patients was there a
      significant negative correlation between Dkk-1 and TBS values (p < 0.0001). The
      increased Dkk-1 serum levels and decreased TBS values observed suggest a diffuse
      bone damage in SSc patients with advanced disease, as demonstrated by the
      concomitant presence of the "Late" NVC pattern. Moreover, the bone remodeling in
      SSc seems even higher than that in RA patients.

PMID- 30291472
TI  - Effect of achieved hemoglobin level on renal outcome in non-dialysis chronic
      kidney disease (CKD) patients receiving epoetin beta pegol: MIRcerA CLinical
      Evidence on Renal Survival in CKD patients with renal anemia (MIRACLE-CKD Study).
AB  - BACKGROUND: Previous randomized-controlled trials have shown that targeting
      higher hemoglobin (Hb) levels using high dose of ESA in non-dialysis chronic
      kidney disease (NDCKD) patients resulted in poorer cardiovascular outcome;
      however, it remains unknown how high Hb levels achieved by ESA in clinical
      practice dose could affect renal outcome. METHODS: In a multicenter prospective
      observational study, Japanese NDCKD patients with an estimated glomerular
      filtration rate (eGFR) of >= 6 mL/min/1.73 m2 and renal anemia (Hb < 11 g/dL)
      treated with epoetin beta pegol (C.E.R.A.) for the first time were divided into
      two groups by Hb level (< 11 g/dL or >= 11 g/dL) in Week 12 of C.E.R.A. treatment
      (Week 12 Hb). Renal outcome was defined as time until the first occurrence of one
      of the following: progression to renal replacement therapy, serum creatinine
      doubling, or eGFR falling below 6 mL/min/1.73 m2. The effect of Week 12 Hb on the
      onset of renal events was assessed by the Kaplan-Meier and multivariate Cox
      regression analyses. RESULTS: In the landmark analysis which included 2851
      patients, Kaplan-Meier renal survival rate was 37.57% in the < 11 g/dL group and
      was significantly higher (51.47%) in the >= 11 g/dL group (P < 0.0001).
      Multivariate Cox regression analysis revealed significantly higher risk of renal
      events in the < 11 g/dL group than in the >= 11 g/dL group (hazard ratio: 1.26;
      95% confidence interval: 1.05-1.51; P = 0.0103). CONCLUSIONS: The results suggest
      that week 12 Hb levels >= 11 g/dL achieved with C.E.R.A. treatment were
      associated with better renal outcomes than Hb levels < 11 g/dL.

PMID- 30291473
TI  - The urate-lowering efficacy and safety of febuxostat versus allopurinol in
      Chinese patients with asymptomatic hyperuricemia and with chronic kidney disease
      stages 3-5.
AB  - BACKGROUND: While the dose of allopurinol is limited in patients with chronic
      kidney disease (CKD), information is lacking concerning the efficacy, safety, and
      maintenance dose of febuxostat in Chinese patients with hyperuricemia and with
      CKD stages 3-5. METHODS: A single center, prospective cohort study was conducted
      in patients with CKD stages 3-5 and with hyperuricemia who had not yet begun to
      undergo renal replacement therapy. We enrolled 208 patients who were newly
      treated with febuxostat (n = 112) or allopurinol (n = 96) in this study. The
      efficacy of febuxostat was determined by the proportion of patients with serum
      uric acid (sUA) < 360 umol/L at the end of the study and changes of renal
      function. RESULTS: The target of sUA < 360 umol/L was reached by 96.4% of
      participants in the febuxostat group and 37.5% in the allopurinol group at 6
      months. The eGFR in the febuxostat group showed an increase from 28.45 to 30.65
      mL/min/1.73 m2 at 6 months, while in the allopurinol group, the eGFR decreased
      from 28.06 to 24.39 mL/min/1.73 m2. Linear regression analysis showed that the
      reduction in sUA was significantly associated with an increase in eGFR and
      decrease in proteinuria. We found that 83.0% of the patients could remain with
      sUA < 360 umol/L at a maintenance dose of febuxostat 20 mg/day. CONCLUSION:
      Febuxostat had superior urate-lowering efficacy to that of allopurinol in Chinese
      Han patients with hyperuricemia with CKD stages 3-5, and the reduction in sUA
      levels was associated with a slower progression of renal function.

PMID- 30291474
TI  - Macaca arctoides gammaherpesvirus 1 (strain herpesvirus Macaca arctoides): virus
      sequence, phylogeny and characterisation of virus-transformed macaque and rabbit
      cell lines.
AB  - Herpesvirus Macaca arctoides (HVMA) has the propensity to transform macaque
      lymphocytes to lymphoblastoid cells (MAL-1). Inoculation of rabbits with cell
      free virus-containing supernatant resulted in the development of malignant
      lymphomas and allowed isolation of immortalised HVMA-transformed rabbit
      lymphocytes (HTRL). In this study, the HVMA genome sequence (approx. 167 kbp),
      its organisation, and novel aspects of virus latency are presented. Ninety-one
      open reading frames were identified, of which 86 were non-repetitive. HVMA was
      identified as a Lymphocryptovirus closely related to Epstein-Barr virus,
      suggesting the designation as 'Macaca arctoides gammaherpesvirus 1' (MarcGHV-1).
      In situ lysis gel and Southern blot hybridisation experiments revealed that the
      MAL-1 cell line contains episomal and linear DNA, whereas episomal DNA is
      predominantly present in HTRL. Integration of viral DNA into macaque and rabbit
      host cell genomes was demonstrated by fluorescence in situ hybridisation on
      chromosomal preparations. Analysis of next-generation sequencing data confirmed
      this finding. Approximately 400 read pairs represent the overlap between macaque
      and MarcGHV-1 DNA. Both, MAL-1 cells and HTRL show characteristics of a
      polyclonal tumour with B- and T-lymphocyte markers. Based on analysis of viral
      gene expression and immunohistochemistry, the persistence of MarcGHV-1 in MAL-1
      cells resemble the latency type III, whereas the expression pattern observed in
      HTRL was more comparable with latency type II. There was no evidence of the
      presence of STLV-1 proviral DNA in MAL-1 and HTRL. Due to the similarity to EBV
      mediated cell transformation, MarcGHV-1 expands the available in vitro models by
      simian and rabbit cell lines.

PMID- 30291475
TI  - Biogenic Au@ZnO core-shell nanocomposites kill Staphylococcus aureus without
      provoking nuclear damage and cytotoxicity in mouse fibroblasts cells under
      hyperglycemic condition with enhanced wound healing proficiency.
AB  - The aim of the present study is focused on the synthesis of Au@ZnO core-shell
      nanocomposites, where zinc oxide is overlaid on biogenic gold nanoparticles
      obtained from Hibiscus Sabdariffa plant extract. Optical property of
      nanocomposites is investigated using UV-visible spectroscopy and crystal
      structure has been determined using X-ray crystallography (XRD) technique. The
      presence of functional groups on the surface of Au@ZnO core-shell nanocomposites
      has been observed by Fourier transforms infrared (FTIR) spectroscopy. Electron
      microscopy studies revealed the morphology of the above core-shell
      nanocomposites. The synthesized nanocomposite material has shown antimicrobial
      and anti-biofilm activity against Staphylococcus aureus and Methicillin Resistant
      Staphylococcus haemolyticus (MRSH). The microbes are notorious cross contaminant
      and are known to cause infection in open wounds. The possible antimicrobial
      mechanism of as synthesized nanomaterials has been investigated against
      Staphylococcus aureus and obtained data suggests that the antimicrobial activity
      could be due to release of reactive oxygen species (ROS). Present study has
      revealed that surface varnishing of biosynthesized gold nanoparticles through
      zinc oxide has improved its antibacterial proficiency against Staphylococcus
      aureus, whereas reducing its toxic effect towards mouse fibroblast cells under
      normal and hyperglycaemic condition. Further studies have been performed in mice
      model to understand the wound healing efficiency of Au@ZnO nanocomposites. The
      results obtained suggest the possible and effective use of as synthesized core
      shell nanocomposites in wound healing.

PMID- 30291476
TI  - Developmental venous anomalies and brainstem cavernous malformations: a proposed
      physiological mechanism for haemorrhage.
AB  - The incidental diagnosis of both developmental venous anomalies (DVAs) and
      cavernous malformations (CMs) in the central nervous system is increasing with
      improved imaging techniques. While classically silent diseases, these
      cerebrovascular pathologies can follow an aggressive course, particularly when
      present in the brainstem. In the last decade, substantial research has focussed
      on KRIT1-mediated tight junction gene expression and their role in CM
      development. However, our understanding of the physiologic conditions
      precipitating symptomatic CM development or CM haemorrhage with and without
      concomitant DVAs, remains lacking. The only established risk factor for CM
      haemorrhage is a previous history of haemorrhage, and literature currently
      reports trauma as the only precipitant for symptomatic events. While plausible,
      this occurs in a minority, with many patients experiencing occult events. This
      manuscript presents a hypothesis for symptomatic CM events by first discussing
      the anatomical pathways for intracranial venous outflow via the internal jugular
      veins (IJV) and vertebral venous plexus (VVP), then exploring the role of venous
      flow diversion away from the IJVs under physiologic stress during dynamic
      postural shift. The resultant increase in intracranial venous pressure can
      exacerbate normal and pre-existing structural DVA pathologies, with repeated
      exposure causing symptomatic or CM-inducing events. This pathophysiological model
      is considered in the context of the role of the autonomic nervous system (ANS) in
      postural intracranial venous outflow diversion, and how this may increase the
      risk of DVA or CM events. It is hoped that this hypothesis invokes further
      investigation into precipitants for DVA or CM events and their sequela and, also,
      furthers the current knowledge on pathophysiological development of DVAs and CMs.

PMID- 30291477
TI  - Towards Accurate Segmentation of Retinal Vessels and the Optic Disc in
      Fundoscopic Images with Generative Adversarial Networks.
AB  - Automatic segmentation of the retinal vasculature and the optic disc is a crucial
      task for accurate geometric analysis and reliable automated diagnosis. In recent
      years, Convolutional Neural Networks (CNN) have shown outstanding performance
      compared to the conventional approaches in the segmentation tasks. In this paper,
      we experimentally measure the performance gain for Generative Adversarial
      Networks (GAN) framework when applied to the segmentation tasks. We show that GAN
      achieves statistically significant improvement in area under the receiver
      operating characteristic (AU-ROC) and area under the precision and recall curve
      (AU-PR) on two public datasets (DRIVE, STARE) by segmenting fine vessels. Also,
      we found a model that surpassed the current state-of-the-art method by 0.2 - 1.0%
      in AU-ROC and 0.8 - 1.2% in AU-PR and 0.5 - 0.7% in dice coefficient. In
      contrast, significant improvements were not observed in the optic disc
      segmentation task on DRIONS-DB, RIM-ONE (r3) and Drishti-GS datasets in AU-ROC
      and AU-PR.

PMID- 30291478
TI  - The Radiologist's Gaze: Mapping Three-Dimensional Visual Search in Computed
      Tomography of the Abdomen and Pelvis.
AB  - A radiologist's search pattern can directly influence patient management. A
      missed finding is a missed opportunity for intervention. Multiple studies have
      attempted to describe and quantify search patterns but have mainly focused on
      chest radiographs and chest CTs. Here, we describe and quantify the visual search
      patterns of 17 radiologists as they scroll through 6 CTs of the abdomen and
      pelvis. Search pattern tracings varied among individuals and remained relatively
      consistent per individual between cases. Attendings and trainees had similar eye
      metric statistics with respect to time to first fixation (TTFF), number of
      fixations in the region of interest (ROI), fixation duration in ROI, mean
      saccadic amplitude, or total number of fixations. Attendings had fewer numbers of
      fixations per second versus trainees (p < 0.001), suggesting efficiency due to
      expertise. In those cases that were accurately interpreted, TTFF was shorter (p =
      0.04), the number of fixations per second and number of fixations in ROI were
      higher (p = 0.04, p = 0.02, respectively), and fixation duration in ROI was
      increased (p = 0.02). We subsequently categorized radiologists as "scanners" or
      "drillers" by both qualitative and quantitative methods and found no differences
      in accuracy with most radiologists being categorized as "drillers." This study
      describes visual search patterns of radiologists in interpretation of CTs of the
      abdomen and pelvis to better approach future endeavors in determining the effects
      of manipulations such as fatigue, interruptions, and computer-aided detection.

PMID- 30291479
TI  - Neural networks of aggression: ALE meta-analyses on trait and elicited
      aggression.
AB  - There is considerable evidence that emotion dysregulation and self-control
      impairments lead to escalated aggression in populations with psychiatric
      disorders. However, convergent quantitative evidence on the neural network
      explaining how aggression arises is still lacking. To address this gap, peak
      activations extracted from extant functional magnetic resonance imaging (fMRI)
      studies were synthesized through coordinate-based meta-analyses. A systematic
      search in the PubMed database was conducted and 26 fMRI studies met the inclusion
      criteria. Three separate activation likelihood estimation (ALE) meta-analyses
      were performed on (1) individual differences in trait aggression (TA) studies,
      (2) individual differences in TA studies examining executive functioning, and (3)
      elicited aggression (EA) studies across fMRI behavioral paradigms. Ensuing
      clusters from ALE meta-analyses were further treated as seeds for follow-up
      investigations on consensus connectivity networks (CCN) delineated from meta
      analytic connectivity modeling (MACM) and resting-state functional connectivity
      (RSFC) to further characterize their physiological functions. Finally, we
      obtained a data-driven functional characterization of the ensuing clusters and
      their networks. This approach offers a boarder view of the ensuing clusters using
      a boarder network perspective. In TA, aberrant brain activations were found only
      in the right precuneus. Follow-up analyses revealed that the precuneus seed was
      within the frontal-parietal network (FPN) associated with action inhibition,
      visuospatial processing and higher-level cognition. With further restricting to
      only experiments examining executive functioning, convergent evidence was found
      in the right rolandic operculum (RO), midcingulate cortex (MCC), precentral gyrus
      (PrG) and precuneus. Follow-up analyses suggested that RO, MCC and PrG may belong
      to a common cognitive control network, while the MCC seems to be the hub of this
      network. In EA, we only revealed a convergent region in the left postcentral
      gyrus. Follow-up CCN analyses and functional characterizations suggested that
      this region may also belong to the same cognitive control network found in the TA
      sub-analysis. Our results suggested that escalated aggression arises from
      abnormal precuneus activities within the FPN, disrupting the recruitment of other
      large-scale networks such as adaptive cognitive control network. Consequently,
      failure to recruit such a network results in an inability to generate adaptive
      responses, increasing the likelihood of acting aggressively.

PMID- 30291480
TI  - TMS of the occipital face area modulates cross-domain identity priming.
AB  - Accumulating evidence suggests that besides its function in early facial feature
      processing, the role of the right occipital face area (rOFA) extends to higher
      level, image-independent processing. Recent studies hint at the possibility that
      the activity of this region can be modulated by semantic information as well. To
      test whether the OFA is sensitive to semantic information in a functionally
      relevant way, we implemented a cross-domain, name-face priming paradigm combined
      with state-dependent transcranial magnetic stimulation, whereby stimulation
      preferentially facilitates the processing of attributes encoded by less active
      neural populations. Our volunteers performed a familiarity decision task for
      target face images preceded by primes that were either the name of the same
      identity (congruent), a name of a different person (incongruent), or the
      character string 'XXXXX' (no prime). Stimulating the rOFA at target stimulus
      onset, we observed the disappearance of the behavioral disadvantage of
      incongruent primes, compared to the vertex control condition. Performance in the
      congruent and no prime conditions remained intact. This result suggests the
      existence of neural populations in the rOFA that take part in the semantic
      processing of identity, probably in interplay with other nodes in the extended
      face network.

PMID- 30291481
TI  - Reply to letter to the editor.

PMID- 30291483
TI  - Rectal vs. sublingual misoprostol before cesarean section: double-blind, three
      arm, randomized clinical trial.
AB  - PURPOSE: The commonest surgical procedure for women is cesarean delivery.
      Postpartum hemorrhage and intra-operative blood during cesarean delivery is a
      major concern to all obstetricians. This study was conducted to assess the
      efficacy of the adjuvant use of misoprostol and oxytocin in decreasing intra
      operative blood loss in cesarean delivery. METHODS: This was a double-blinded
      randomized clinical trial including 636 term pregnant woman scheduled for
      cesarean section at Ain Shams University Maternity Hospital, Cairo, Egypt,
      between February 2013 and February 2014. Participants received either 400-MUg
      misoprostol rectally or sublingually or placebo before cesarean section together
      with 5-IU oxytocin IV. The main outcome measure was intra-operative blood loss.
      Difference between the three groups was analyzed using one-way ANOVA test (for
      numeric variables) and Chi-square test (for categorical variables). P < 0.05 was
      considered statistically significant. RESULTS: Intra-operative blood loss was
      higher in patients who did not receive misoprostol (Placebo Group) (295-1075 ml,
      641.7 +/- 135.7) than those who received it, regardless the route of
      administration, rectal (135-830 ml, 457.5 +/- 140.7; P < 0.001), and sublingual
      (135-680 ml, 357.8 +/- 129.7; P < 0.001). In addition, sublingual route was
      associated with significantly lower estimated intra-operative blood loss compared
      to rectal administration (P < 0.001). CONCLUSIONS: Misoprostol with oxytocin is
      an effective drug-combination for decreasing intra-operative blood loss during
      cesarian section with clinical superiority to sublingual over rectal route.

PMID- 30291482
TI  - Effect of intrauterine injection of human chorionic gonadotropin before fresh
      embryo transfer on IVF and ICSI outcomes: a meta-analysis.
AB  - PURPOSE: This analysis was performed to evaluate the effects of intrauterine
      injection of human chorionic gonadotropin (hCG) before fresh embryo transfer (ET)
      on the outcomes of in vitro fertilization and intracytoplasmic sperm injection.
      METHODS: Randomized controlled trials (RCTs) were identified by searching
      electronic databases. The outcomes of live birth, clinical pregnancy,
      implantation, biochemical pregnancy, ongoing pregnancy, ectopic pregnancy, and
      miscarriage between groups with and without hCG injections were analyzed. Summary
      measures were reported as risk ratios (RR) with 95% confidence intervals.
      RESULTS: Six RCTs on fresh embryo transfer (ET) were included in the meta
      analysis. A total of 2759 women undergoing fresh ET were enrolled (hCG group n =
      1429; control group n = 1330). Intrauterine injection of hCG significantly
      increased rates of biochemical pregnancy (RR 1.61) and ongoing pregnancy (RR
      1.58) compared to controls. However, there were no significant differences in
      clinical pregnancy (RR 1.11), implantation (RR 1.17), miscarriage (RR 0.91),
      ectopic (RR 1.65) or live birth rates (RR 1.13) between the hCG group and control
      group. CONCLUSION: The current evidence for intrauterine injection of hCG before
      fresh ET does not support its use in an assisted reproduction cycle.

PMID- 30291484
TI  - Birthweight thresholds for increased risk for maternal and neonatal morbidity
      following vaginal delivery: a retrospective study.
AB  - PURPOSE: To determine neonatal birthweight (BW) thresholds for adverse maternal
      and neonatal outcome following vaginal delivery. METHODS: A retrospective cohort
      study of all women with singleton pregnancies who underwent vaginal delivery in a
      university-affiliated tertiary hospital (1996-2015). The association between BW
      and adverse outcome in neonates with BW >= 3500 g (> 90th centile BW at 37 weeks'
      gestation) with 100 g-increment groups was explored. Pregnancies complicated by
      diabetes mellitus, fetal anomalies or cesarean deliveries were excluded. The
      composite neonatal outcome was defined as shoulder dystocia or brachial plexus
      injury. The composite maternal outcome was defined as postpartum hemorrhage or
      third- or fourth-degree perineal tears. RESULTS: Of the 121,728 deliveries during
      the study period, 26,920 (22.1%) met inclusion criteria. Of these, 1024 (3.8%)
      had a composite adverse maternal outcome and 947 (3.5%) had a composite adverse
      neonatal outcome. The rates of composite maternal outcomes increased
      significantly only at a BW of 4800 g and above. The composite neonatal outcomes
      increased significantly only at a BW of 4400 g and above. In multivariate
      analysis, after subcategorizing our cohort into 3 BW groups [3500-3999 g
      (control, n = 23,030); 4000-4399 g (n = 3494); >= 4400 g (n = 396)], BW was
      associated with adverse neonatal outcomes in a dose-dependent manner. In the BW
      >= 4400 g group, to prevent one case of shoulder dystocia or Erb's palsy, 12
      cesarean deliveries needed to be performed. CONCLUSION: For non-diabetic mothers
      who deliver vaginally, neonatal BW >= 4400 g was associated with a significant
      increase in adverse neonatal outcomes, whereas neonatal BW >= 4800 g was
      associated with a significant increase in adverse maternal outcomes.

PMID- 30291485
TI  - The Molecular Identification and Antifungal Susceptibilities of Aspergillus
      Species Causing Otomycosis in Tochigi, Japan.
AB  - Aspergillus species are the most common pathogenic fungi involved in otomycosis,
      an infection of the outer ear canal. In this study, we examined the incidence of
      Aspergillus infections and the antifungal susceptibilities of 30 Aspergillus
      species isolates from patients with otomycosis who visited Saiseikai Utsunomiya
      Hospital between August 2013 and July 2016. Based on the morphological test
      results, the strains were identified as Aspergillus niger sensu lato (20
      strains), A. terreus sensu lato (7 strains), and A. fumigatus sensu lato (3
      strains). In contrast, the molecular identifications based on analyzing the
      isolates' partial beta-tubulin gene sequences revealed them to be A. niger sensu
      stricto (12 strains), A. tubingensis (8 strains), A. terreus sensu stricto (7
      strains), and A. fumigatus sensu stricto (3 strains). The antifungal
      susceptibility test results indicated that strains of A. tubingensis and A. niger
      sensu stricto displayed lower susceptibilities to ravuconazole, compared with the
      other isolates. The Aspergillus strains from this study showed low minimum
      inhibitory concentrations toward the azole-based drugs efinaconazole,
      lanoconazole, and luliconazole. Therefore, these topical therapeutic agents may
      be effective for the treatment of otomycosis.

PMID- 30291486
TI  - Familias Unidas for Health and Wellness: Adapting an Evidence-Based Substance Use
      and Sexual Risk Behavior Intervention for Obesity Prevention in Hispanic
      Adolescents.
AB  - We describe the adaptation of Familias Unidas, an evidence-based substance use
      and sexual risk behavior intervention, for obesity prevention in Hispanic
      adolescents. Intervention developers and experts in pediatric obesity, exercise
      physiology, dietetics, and the local parks system provided input for changes.
      Hispanic families also provided input through a series of 21 focus groups
      conducted before, during, and after an initial pilot test of the adapted
      intervention. After transcribing audiotaped sessions, we used a general inductive
      approach and Dedoose qualitative software to derive themes. Results indicated the
      need for improved health-related family functioning, enhanced nutrition education
      and skill building, increased family engagement in physical activity, and
      stronger links between family and environmental supports. Parents who
      participated in the pilot test expressed high enthusiasm for hands-on nutrition
      training and reported improvements in family functioning. Adolescents liked
      outdoor physical activities but wanted parents to be more engaged in joint
      physical activity sessions. The adapted intervention maintains fidelity to
      Familias Unidas' core theoretical elements and overall structure, but also
      includes content focused on physical activity and nutrition, adolescent
      participation in physical activity sessions led by park coaches, and joint parent
      adolescent participation in physical activity and nutrition skill-building
      activities.

PMID- 30291487
TI  - Study of kinetics of 19F-MRI using a fluorinated imaging agent (19FIT) on a 3T
      clinical MRI system.
AB  - PURPOSE: To use 19F imaging tracer (19FIT-27) to evaluate kinetics in major
      organs. INTRODUCTION: Kinetics studies using proton MRI are difficult because of
      low concentration of 19FIT-27 protons relative to background water protons.
      Because there is no background source of 19F NMR in a biological body, 19F may be
      an ideal nucleus to directly trace 19FIT-27. However, there are several
      challenges for reliable 19F MR imaging and spectroscopy, particularly with
      clinical whole-body MRI systems, which include low concentrations and long 19F
      T1. METHODS AND MATERIALS: We performed a dynamic 19F MRI study on mice at a 3T
      whole-body MRI system using a homemade transmit/receive (Tx/Rx) switch and a
      Tx/Rx volume RF coil. We used a newly developed fluorine imaging agent, which has
      27 identical fluorine atoms with identical chemical shift, a relatively short T1,
      and high hydrophilicity. Basic kinetics parameters were estimated from the 19F
      signal-time curve. RESULTS AND DISCUSSIONS: Resultant fluorine images show fairly
      high spatial (3 * 3 * 3 mm3) and temporal resolutions. Biodistribution and
      kinetics of 19FIT-27 are obtained via 19F images for major uptake organs.
      CONCLUSIONS: Whole-body dynamic 19F MRI of newly developed 19FIT-27 in mice was
      obtained with fairly high spatial and temporal resolutions on a 3T clinical MRI
      system. The present study demonstrates the feasibility of 19F MRI using our newly
      developed compound to investigate major organ kinetics.

PMID- 30291488
TI  - Association between clusterin concentration and dementia: a systematic review and
      meta-analysis.
AB  - Studies have showed that high clusterin (CLU) concentration was associated with
      increased risk of dementia. However, the results based on small samples remained
      controversial. The aim of our study was to determine the relationship between CLU
      concentration and the late-life cognitive outcomes including mild cognitive
      impairment (MCI), Alzheimer's disease (AD), vascular dementia (VAD), Parkinson's
      disease related dementia (PDD), Lewy body dementia (DLB) and frontotemporal
      dementia (FTD). A comprehensive search was conducted to screen the eligible
      studies in online database PubMed, Web of Science and Embase from 1950 to January
      2017 according to the preferred reporting items for systematic reviews and meta
      analyses (PRISMA) checklist. The CLU concentration data in brain tissue,
      cerebrospinal fluid (CSF), serum and plasma was collected to determine the
      strength of this association. The results were presented with standard difference
      of the mean (SDM) with 95% confidence intervals (CIs). A total of 28 studies were
      identified to calculate the association between CLU concentration and dementia.
      The results showed that the CLU concentration in the plasma (SDM = 0.73, 95% CI
      0.26-1.19, P = 0.002) and brain tissue (SDM = 0.71, 95% CI 0.10-1.32, P = 0.022)
      was increased in dementia compared to normal control. Subgroup analysis showed
      that the plasma CLU concentration was significantly increased only in the AD
      group (SDM = 1.85, 95% CI 0.84-2.85, P < 0.001), but not in MCI or other
      dementias. No association was found between serum and CSF clusterin concentration
      and dementia. This meta-analysis indicates that high CLU concentration in the
      plasma and brain is associated with dementia, especially in AD.

PMID- 30291489
TI  - Rescue Nuss procedure for inferior vena cava compression syndrome following
      posterior scoliosis surgery in Marfan syndrome.
AB  - PURPOSE: Scoliosis surgery in Marfan syndrome is common, even in the presence of
      a funnel chest. However, to date, no case has been reported with acute intra
      /postoperative decompensation caused by vena cava compression following posterior
      spinal derotation and fusion. METHODS: A 15-year-old male patient with Marfan
      syndrome, a funnel chest and severe scoliosis was treated with surgery for the
      spinal deformity. Intraoperatively, the patient developed a clinically relevant
      compression of the inferior vena cava with severe circular depression.
      Postoperatively, a cava compression syndrome with severe pleural effusion,
      ascites and enormous swelling of the lower limbs was developed. A conservative
      treatment of the symptoms, consisting of thoracic drainage and negative fluid
      balance, failed. Subsequently, the patient was transferred to pediatric intensive
      care unit for further treatment. Echocardiography and a CT scan demonstrated cava
      compression syndrome. A rescue Nuss procedure of the funnel chest deformity was
      performed since conservative treatment failed. The clinical course proceeded
      without complications and with a decrease in clinical symptoms of inferior inflow
      congestion. The patient was discharged after almost 3 weeks. CONCLUSION: The
      problem of congenital stenosis of the inferior vena cava in Marfan syndrome has
      not yet been investigated. In the case of simultaneously existing funnel chest
      and scoliosis in Marfan syndrome, an interdisciplinary discussion is required to
      decide whether a repair of the funnel chest should be performed first in order to
      prevent a clinically relevant compression syndrome. For the detection of a
      preoperatively relevant stenosis of the inferior vena cava, an MRI or
      thoracic/abdominal CT should be used preoperatively.

PMID- 30291491
TI  - Avidekel Cannabis extracts and cannabidiol are as efficient as Copaxone in
      suppressing EAE in SJL/J mice.
AB  - Multiple sclerosis (MS) is an autoimmune disease leading to the destruction of
      myelin with consequent axonal degeneration and severe physical debilitation. The
      disease can be treated with immunosuppressive drugs that alleviate the symptoms
      and retard disease aggravation. One such drug in clinical use is glatiramer
      acetate (Copaxone). The non-psychotropic immunosuppressive cannabinoid compound
      cannabidiol (CBD) has recently been shown to have beneficial effects on
      experimental autoimmune encephalomyelitis (EAE). The aim of our study was to
      compare the efficacy of CBD and standardized extracts from a CBD-rich, ?9-THClow
      Cannabis indica subspecies (Avidekel) with that of Copaxone. Our data show that
      CBD and purified Avidekel extracts are as efficient as Copaxone to alleviate the
      symptoms of proteolipid protein (PLP)-induced EAE in SJL/J mice. No synergistic
      effect was observed by combining CBD or Avidekel extracts with Copaxone. Our data
      support the use of Avidekel extracts in the treatment of MS symptoms.

PMID- 30291490
TI  - Immunomodulatory properties of captopril, an ACE inhibitor, on LPS-induced lung
      inflammation and fibrosis as well as oxidative stress.
AB  - BACKGROUND: The role of angiotensin converting enzyme inhibitors on the
      inflammation process has been demonstrated previously. In the present study, the
      effects of captopril on lung injury induced by lipopolysaccharide (LPS) were
      investigated. METHODS: Control, LPS, 12.5, 25 and 50 mg/kg captopril-treated
      before LPS administration and captopril 50 mg/kg before saline administration
      groups of rats were studied. Total and percentage of differential WBC, the levels
      of MDA, total thiol groups, the activities of SOD and CAT, the levels of IFN
      gamma, PGE2, TGF-beta1 and IL-4 in the BALF were evaluated. RESULTS: MDA
      concentration in LPS groups treated with all captopril concentrations, total WBC
      in LPS + Cap50, percent of neutrophils in LPS + Cap25 and LPS + Cap50, levels of
      IFN-gamma, PGE2, TGF-beta1 in LPS + Cap50 and IFN-gamma/IL-4 ratio in LPS + Cap25
      and LPS + Cap50 were significantly decreased but total thiol groups and activity
      of SOD in LPS + Cap25 and LPS + Cap50, percent of lymphocyte, CAT activity and
      concentration of IL-4 only in LPS + Cap50 group were increased in comparison to
      the LPS group (p < 0.05 to p < 0.001). CONCLUSION: Captopril dose dependently
      improved oxidant-antioxidant biomarkers, the imbalance between pro-inflammatory
      and anti-inflammatory cytokines and showed specific immunomodulatory effect on
      Th1/Th2 balance in the BALF of lung injury induced by LPS.

PMID- 30291492
TI  - Neuronal Responses of Antennal Olfactory Sensilla to Insect Chemical Repellents
      in the Yellow Fever Mosquito, Aedes aegypti.
AB  - The yellow fever mosquito, Aedes aegypti, is a vector of many human diseases such
      as yellow fever, dengue fever, and Zika. As insecticide resistance has been
      widely reported, chemical repellents have been adopted as alternative options for
      mosquito and mosquito-borne disease control. This study characterized the
      responses of olfactory receptor neurons (ORNs) in different types of antennal
      olfactory sensilla in Ae. aegypti to 48 chemicals that exhibited repellent
      activity in various insect species. Both excitatory and inhibitory responses were
      observed from ORNs in response to these chemicals and differential tuning
      properties were also observed among ORNs. Remarkable excitatory responses were
      recorded from the ORNs in sensilla SST1, SST2, SBTI, SBTII, and LST2, while
      inhibitory activities were detected from a neuron in sensillum SST2 in response
      to several terpene/terpenoid compounds. Moreover, the temporal dynamics of
      neuronal responses were found to be compound-specific and concentration
      dependent. Hierarchical cluster analysis and principal component analysis of the
      response to each compound across ORNs in seven types of olfactory sensilla in Ae.
      aegypti revealed that odor reception depended not only on chemical class but also
      specific chemical structure. Results of this study give new insights into the
      sensory physiology of Aedes mosquitoes to the chemical repellents and should
      contribute to the development of new repellent reagents for human protection.

PMID- 30291493
TI  - Characteristics, treatment and outcome of bleeding after tooth extraction in
      patients on DOAC and phenprocoumon compared to non-anticoagulated patients-a
      retrospective study of emergency department consultations.
AB  - OBJECTIVES: Bleeding after tooth extraction range from minor bleeding to life
      threating haemorrhagic shock and are among the leading complications in patients
      under oral anticoagulation with direct oral anticoagulants (DOACs) or
      phenprocoumon. Little is known about how anticoagulation in patients under DOAC
      or phenprocoumon alters the characteristics, treatment or outcome of bleeding
      events, in comparison to non-anticoagulated patients. METHODS: Patients admitted
      to a tertiary ED in Bern, Switzerland, from June 1st 2012 to 31st May 2016 with
      bleeding related to tooth extraction under DOAC, phenprocoumon or without
      anticoagulation, were compared. RESULTS: Out of 161,458 emergency consultations,
      64 patients with bleeding from tooth extraction were included in our study. In
      anticoagulation groups, we found significantly more delayed bleeding events than
      in patients without anticoagulation (9 (81.3%) DOAC, 19 (86.4%) phenprocoumon, 8
      (30.8%) no anticoagulation, p < 0.001). Anticoagulated patients had to stay
      longer in the ED than non-anticoagulated patients, with no significant difference
      between DOAC or phenprocoumon (hours: 4.8 (3.2-7.6 IQR) DOAC, 3.0 (2.0-5.5 IQR)
      phenprocoumon, p = 0.133; 2.7 (1.6-4.6) no anticoagulation; p = 0.039). More
      patients with anticoagulation therapy needed surgery than patients without
      anticoagulant therapy (11 (68.8%) DOAC, 12 (54.6%) VKA, p = 0.506; 7(26.9%) no
      anticoagulation; p = 0.020). CONCLUSIONS: Delayed bleeding occur more often in
      anticoagulated patients with both DOAC and phenprocoumon compared to patients
      without anticoagulation. Bleeding events in anticoagulated patients with DOAC and
      phenprocoumon equally need longer ED treatment and more frequent surgical
      intervention. CLINICAL RELEVANCE: Caution with delayed bleeding in anticoagulated
      patients with DOACs and phenprocoumon is necessary and treatment of bleeding is
      resource-demanding.

PMID- 30291494
TI  - Effect of intermittent teriparatide (PTH 1-34) on the alveolar healing process in
      orchiectomized rats.
AB  - OBJECTIVE: To evaluate intermittent teriparatide therapy's influence on the
      alveolar healing process in rats with induced osteoporosis. MATERIALS AND
      METHODS: Fifty-four male rats were divided into three groups: fictitious surgery
      (SHAM), bilateral orchiectomy (ORQ NT), and bilateral orchiectomy treated with
      teriparatide (ORQ TERI). Right upper incisor extraction was performed. After 14
      and 42 days, the rats were euthanized. Immunolabeling analysis was performed in
      order to characterize bone turnover through Wnt, alcaline phosphatase,
      osteocalcin, and TRAP presence in tissue; micro-CT analysis was performed in
      order to determine the bone volume fraction (BV/TV), trabecular thickness,
      separation, and number (Tb.Th, Tb.Sp, Tb.N). For the micro-CT data, statistical
      analysis was performed through one-way ANOVA and Tukey post-test, for
      parametrical data, with significance level adopted in p < 0.05. Days, Wnt,
      alkaline phosphatase, and osteocalcin revealed more labeling for ORQ TERI and
      less for TRAP. For the Tb.N in the ORQ NT group was 0.496 mm, a significant
      statistical difference was observed between the groups of ORQ NT and ORQ TERI (p
      < 0.05). For the BV/TV, Tb.Sp, and Tb.Th parameters, no significant statistical
      difference was observed among the three experimental groups (p > 0.05).
      CONCLUSIONS: Treatment with intermittent teriparatide reverted impairment in the
      metabolism of repairing bone tissue in orchiectomized animals. CLINICAL
      RELEVANCE: Cases of decreased bone density such as osteoporosis can lead to
      delayed alveolar repair process. PTH 1-34 has been shown to be a medication that
      improves this repair, making bone of low quality into one with normal features.

PMID- 30291495
TI  - Prevention of oral carcinogenesis in rats by Dracaena cinnabari resin extracts.
AB  - OBJECTIVES: In vivo study was performed to determine the chemopreventive efficacy
      of the DC resin methanol extract on a 4-nitroquinoline-1-oxide (4NQO) oral cancer
      animal model. MATERIALS AND METHODS: This study involves administration of 4NQO
      solution for 8 weeks alone (cancer induction) or with Dracaena cinnabari (DC)
      extract at 100, 500, and 1000 mg/kg. DC extract administration started 1 week
      before exposure until 1 week after the carcinogen exposure was stopped. All rats
      were sacrificed after 22 weeks, and histological analysis was performed to assess
      any incidence of pathological changes. Immunohistochemical expressions of
      selected tumor marker antibodies were analyzed using an image analyzer computer
      system, and the expression of selected genes involved in apoptosis and
      proliferative mechanism related to oral cancer were evaluated using RT2-PCR.
      RESULTS: The incidence of OSCC decreased with the administration of DC extract at
      100, 500, and 1000 mg/kg compared to the induced cancer group. The developed
      tumor was also observed to be smaller when compared to the induced cancer group.
      The DC 1000 mg/kg group inhibits the expression of Cyclin D1, Ki-67, Bcl-2, and
      p53 proteins. It was observed that DC 1000 mg/kg induced apoptosis by
      upregulation of Bax and Casp3 genes and downregulation of Tp53, Bcl-2, Cox-2,
      Cyclin D1, and EGFR genes when compared to the induced cancer group. CONCLUSIONS:
      The data indicated that systemic administration of the DC resin methanol extract
      has anticarcinogenic potency on oral carcinogenesis. CLINICAL RELEVANCE:
      Chemoprevention with DC resin methanol extract may significantly reduce morbidity
      and possibly mortality from OSCC.

PMID- 30291496
TI  - Effects of replacing rice bran with tamarind seed meal in concentrate mixture
      diets on the changes in ruminal ecology and feed utilization of dairy steers.
AB  - Feed ingredients costs have been impacting the production cost. Attempts have
      been made to use local feed resources in order to reduce feed costs. The
      objective of this study was to identify effect of using crushed tamarind seed
      meal (TSM) in concentrate mixture on rumen fermentation, dry matter intake, and
      digestibility of dairy steers. Four rumen-fistulated dairy steers were used in a
      4 * 4 Latin Square Design. Four levels of TSM were used to replace rice bran (RB)
      in the concentrate mixtures in four treatments (T1 = 0% replacement of RB, T2 =
      30% replacement of RB, T3 = 60% replacement of RB, T4 = 100% replacement of RB).
      The findings revealed that replacement of TSM for RB resulted in similar
      digestibility of nutrients and intakes (P > 0.05). However, rumen fermentation
      parameters were remarkably improved, namely total VFA and the concentration of C3
      especially at the highest level of replacements (100%, T4), (P < 0.05). Rumen
      protozoal population was found lowered in all replacements, especially those in
      higher levels of TSM replacement. Consequently, the rumen methane productions
      were significantly reduced. TSM can be a promising energy source to replace rice
      bran, hence lowering the cost of concentrate mixture.

PMID- 30291497
TI  - Stability of Autistic Traits from 5 to 8 Years of Age Among Children in the
      General Population.
AB  - Little is known about the across time stability of autistic traits during the
      transition period from preschool to school age in the general population. The
      current study compared autistic traits assessed by a mother-reported quantitative
      measure, the Social Responsiveness Scale, at age 5 and 8 years and examined the
      intraclass correlation coefficients of scores across the period for 168 Japanese
      community-based children. Results showed that total and two subdomain-related
      autistic trait scores remained primarily stable in males and females. This
      stability was observed for both children with higher and lower autistic traits
      scores with a possible sex-specific pattern. Our findings suggest that autistic
      traits in the general population can be reliably assessed using quantitative
      measures for this age period.

PMID- 30291498
TI  - Dissecting Tissue-Specific Super-Enhancers by Integrating Genome-Wide Analyses
      and CRISPR/Cas9 Genome Editing.
AB  - Recent advances in genome-wide sequencing technologies have provided researchers
      with unprecedented opportunities to discover the genomic structures of gene
      regulatory units in living organisms. In particular, the integration of ChIP-seq,
      RNA-seq, and DNase-seq techniques has facilitated the mapping of a new class of
      regulatory elements. These elements, called super-enhancers, can regulate cell
      type-specific gene sets and even fine-tune gene expression regulation in response
      to external stimuli, and have become a hot topic in genome biology. However,
      there is scant genetic evidence demonstrating their unique biological relevance
      and the mechanisms underlying these biological functions. In this review, we
      describe a robust genome-wide strategy for mapping cell-type-specific enhancers
      or super-enhancers in the mammary genome. In this strategy, genome-wide screening
      of active enhancer clusters that are co-occupied by mammary-enriched
      transcription factors, co-factors, and active enhancer marks is used to identify
      bona fide mammary tissue-specific super-enhancers. The in vivo function of these
      super-enhancers and their associated regulatory elements may then be investigated
      in various ways using the advanced CRISPR/Cas9 genome-editing technology. Based
      on our experience targeting various mammary genomic sites using CRISPR/Cas9 in
      mice, we comprehensively discuss the molecular consequences of the different
      targeting methods, such as the number of gRNAs and the dependence on their
      simultaneous or sequential injections. We also mention the considerations that
      are essential for obtaining accurate results and shed light on recent progress
      that has been made in developing modified CRISPR/Cas9 genome-editing techniques.
      In the future, the coupling of advanced genome-wide sequencing and genome-editing
      technologies could provide new insights into the complex genetic regulatory
      networks involved in mammary-gland development.

PMID- 30291499
TI  - The dramatic essence of the narrative approach.
AB  - Even though it is not a methodology on the level of principlism or casuistry,
      narrative bioethics nonetheless contributes to and guides decision-making in the
      field of biomedical ethics. However, unlike other methodologies, the narrative
      approach lacks a set of specific patterns and formal rules for doing so. This
      deficiency leaves this approach more vulnerable to the influence of historical
      factors; in fact, the vital history of a person is made up of thousands of
      scenes, which one must select and group under different norms. Yet the
      historicity of narrative does not destroy its normative value; rather, it gives
      rise to a confluence of stories that contradict one another on the basis of their
      practical consequences. This problem is less severe in traditional cultures,
      where some stories take precedence over others according to the normative value
      conferred through the supposed authority of their sources. But it manifests in an
      intense manner within current multicultural societies. It is imperative to find
      the thread that leads outside the labyrinth of subjectivity. This paper shows
      that the end of this thread lies, paradoxically, not in actions but in the
      subject-actors that perform them-specifically when such subjects are conceived as
      dramaturgical characters in narrative.

PMID- 30291500
TI  - "Tupanvirus", a new genus in the family Mimiviridae.
AB  - The genus "Tupanvirus" is a new proposed taxon to be included in the family
      Mimiviridae. The two known tupanvirus isolates were isolated from soda lake and
      oceanic sediments samples collected in Brazil and were named "tupanvirus soda
      lake" and "tupanvirus deep ocean", respectively. These viruses exhibit
      similarities to amoeba-infecting mimiviruses, but there are also several
      differences that place them in a separate group within the family Mimiviridae.
      Their virions have a mean size of 1.2 um, which include a mimivirus-like capsid
      and a large cylindrical tail, both covered by fibrils. The linear double-stranded
      DNA genomes of up to 1,516,267 base pairs encode over 1,200 genes, among which ~
      30% have no homologs in any database, including in other mimivirus genomes.
      Compared to other mimiviruses, tupanviruses exhibit a broader host range and
      cause a cytotoxic effect in host and non-host organisms, a phenotype that is not
      observed for other mimiviruses. Remarkably, these viruses possess the most
      complete gene set related to the protein synthesis process, including 20
      aminoacyl-tRNA synthetases, 67-70 tRNAs, many translation factors, and genes
      involved in maturation and modification of tRNA and mRNA, among others. Moreover,
      diverse phylogenomic analyses put tupanviruses in a distinct group within the
      family Mimiviridae. In light of the set of different features observed for these
      giant viruses, we propose establishment of a new genus to allow proper
      classification of two known tupanviruses and possibly many more similar viruses
      yet to be characterized.

PMID- 30291501
TI  - Genetic characterization of a novel unique recombinant form of HIV-1 originating
      from subtype A1 and C in Guangdong Province, China.
AB  - The dominant human immunodeficiency virus type 1 (HIV-1) subtypes are CRF01_AE,
      CRF07_BC and CRF08_BC in Guangdong Province, China. In this study, we report a
      unique recombinant form (URF) of HIV-1 that was identified in an HIV/hepatitis B
      virus (HBV)/hepatitis C virus (HCV) triple-infected patient who was an
      intravenous drug user (IDU) in Heyuan City, Guangdong Province. The near full
      length genome was amplified, and the PCR products were sequenced by Sanger's
      method. The Recombination Identification Program (RIP 3.0) and jpHMM online tools
      showed that four subtype C fragments were inserted into the A1 backbone genome in
      the gag, pol, vpr and nef gene regions. In the phylogenetic tree analysis, the
      subtype A1 and C fragments clustered with HIV-1 A1 and C reference sequences,
      respectively. No similar breakpoints between our strain and the other strains in
      the Los Alamos HIV database were observed. The results of evolutionary analysis
      using BEAST software showed that the subtype A1 fragment originated from
      Guangzhou City, China; however, the subtype C fragment originated from East
      Africa. This is the first report of HIV-1 URF A1C in Guangdong Province, China.
      The identification of this URF suggested that further dynamic surveillance of new
      recombinant forms is needed.

PMID- 30291502
TI  - Evidence of avian poxvirus and papillomavirus infection in Gyps fulvus in Italy.
AB  - The identification of avian poxvirus and avian papillomavirus associated with
      cutaneous lesions in griffon vultures (Gyps fulvus) by histopathology, electron
      microscopy and PCR analysis is reported. Sequence analysis of the fpv140 gene
      revealed 99% identity to two poxviruses obtained from a white-tailed sea eagle
      (Haliaeetus albicilla) and a common buzzard (Buteo buteo). Partial sequence of
      the papillomavirus L1 gene showed sequence similarity to papillomavirus LI genes
      from African grey parrot (Psittacus erithacus) (69% identity), duck (Anas
      platyrhynchos) (68% identity), and yellow-necked francolin (Francolinus
      leucoscepus) (66% identity). To date, this is the first identification of avian
      poxvirus and papillomavirus in griffon vultures and the first evidence of
      infection of both viruses in live wild birds.

PMID- 30291503
TI  - Development and comparison of two H5N8 influenza A vaccine candidate strains.
AB  - Avian influenza viruses circulating in birds have caused outbreaks of infection
      in poultry and humans, thereby threatening public health. Recently, a highly
      pathogenic avian influenza (HPAI) virus (H5N8) of clade 2.3.4.4 emerged in Korea
      and other countries and caused multiple outbreaks in domestic and wild birds,
      with concerns for human infection. To combat HPAI viral infections, novel
      vaccines are likely to be the most effective approach. Therefore, in this study,
      we generated H5N8 vaccine candidate viruses based on a Korean isolate (A/broiler
      duck/Korea/Buan2/2014). The vaccine candidate viruses were 2:6 reassortants
      expressing the two surface glycoproteins of A/broiler duck/Korea/Buan2/2014 on an
      A/Puerto Rico/8/34 (PR8) backbone generated by using an eight-plasmid-based
      reverse genetics system with or without replacement of the multi-basic amino acid
      cleavage motif (MBCM, a crucial pathogenic factor in HPAI virus) with a bi-basic
      amino acid cleavage motif (BBCM) in their HA. An H5N8 vaccine candidate virus
      containing the BBCM showed attenuated pathogenesis in embryonated eggs and
      exhibited less virulence in the infected mice compared with the wild H5N8 virus
      containing an MBCM. Vaccination with an inactivated preparation of the vaccine
      candidate virus protected mice from lethal H5N8 viral challenge. This is the
      first report of the development and evaluation of H5N8 vaccine strains (with an
      MBCM or BBCM) of HA clade 2.3.4.4 as vaccine candidates. Our findings suggest
      that H5N8 strains with a BBCM instead of an MBCM might be considered for H5N8
      vaccine seed virus development or as a reference vaccine against H5N8 viral
      strains.

PMID- 30291504
TI  - Crude extracts of recombinant baculovirus expressing rabbit hemorrhagic disease
      virus 2 VLPs from both insect and rabbit cells protect rabbits from rabbit
      hemorrhagic disease caused by RHDV2.
AB  - Vaccines against viral pathogens are often composed of recombinant proteins
      expressed in different systems. Such proteins expressed by recombinant
      baculoviruses have been proven to be effective for vaccination. Especially, after
      codon usage optimization high amounts of recombinant viral proteins can be
      obtained which can assemble to virus like particles (VLPs) spontaneously. In this
      study we compared two different codon usages of RHDV2-VP1 to improve the
      expression of recombinant VP1 of RHDV2 by recombinant baculoviruses after
      infection of insect SF9 cells or transduction of mammalian RK13 cells in order to
      gain high protein yields. Also the influence on the auto-assembly of RHDV2-VP1 to
      VLPs was investigated. Finally, the immunogenic potential of such recombinant
      vaccines against RHDV2 to induce a protective immune response in rabbits against
      RHDV2 should be characterized. There was no influence of different codon usages
      on RHDV2-VP1 gene expression in the respective cell lines detected. However, in
      insect cell line SF9 higher rates of recombinant VP1 were measured in comparison
      to the transduction of mammalian cells RK13. Auto-assembly of RHDV2-VP1 to VLPs
      was observed in both cell systems by electron microscopy. Finally, both RHDV-VP1
      VLPs derived from mammalian and insect cells were able to induce a protective
      humoral immune response in rabbits against RHDV2.

PMID- 30291505
TI  - Phenotypic assortment by body shape in wild-caught fish shoals.
AB  - Phenotypic variation plays a critical role in determining the structural
      organisation and ecological function of wild populations. Animal groups are often
      structured according to factors such as species, sex, body size and parasite
      load, but it is unclear whether body shape also influences patterns of social
      organisation, and thus contributes to population phenotypic structure. Here, we
      use geometric morphometric analyses to determine whether wild-caught shoals of a
      freshwater fish, the western rainbowfish (Melanotaenia australis), are structured
      according to body size and shape. Using randomisation analyses, we show that the
      level of variation in size and shape observed in natural group assemblages is
      lower than that expected under a null model of random shoal composition. In
      addition, we found evidence of further phenotypic structuring along an upstream
      downstream environmental gradient. The putative benefits of morphological
      assortment include a reduction in predation risk (due to prey oddity and predator
      confusion effects) and increased hydrodynamic or foraging efficiency. We suggest
      that morphological variation is a neglected component of population social
      organisation that can affect population processes, such as patterns of gene flow,
      and ecological interactions, such as predator-prey dynamics.

PMID- 30291506
TI  - Multi-criteria Mapping of Stakeholders' Viewpoints in Five Southeast Asian
      Countries on Strategies to Reduce Micronutrient Deficiencies Among Children and
      Women of Reproductive Age: Findings from the SMILING Project.
AB  - BACKGROUND: Despite scientific evidence on the potential impact or importance of
      specific interventions to improve micronutrient status of vulnerable groups,
      political commitment and extensive support from national stakeholders is
      paramount to support introduction and implementation of these interventions at
      national level. In order to develop efficient nutritional strategies to improve
      the micronutrient status of children < 5 years of age and women of reproductive
      age that will be supported by a wide range of stakeholders, a better
      understanding of viewpoints on the nutrition politics and strategies is
      necessary. Multi-criteria mapping (MCM) was successfully used to assess the
      stakeholder's viewpoint in a wide variety of contexts since the late 1990s.
      OBJECTIVE: The objective of the present study was to assess the viewpoints of
      stakeholders on a wide range of potential nutritional interventions in the five
      Southeast Asian countries participating in the SMILING project. METHOD: MCM
      methodology was used to appraise the stakeholder's viewpoints in five countries.
      RESULTS: The results show that the overall stakeholders' preference was for
      actions already implemented in their country rather than for new, innovative
      options, even for supplementation. Indirect interventions such like food
      fortification (except in Indonesia), delayed cord clamping or food-based
      approaches were generally less favored by the stakeholders. However, the majority
      of stakeholders agreed that new approaches should be considered and put in place
      in the future provided that evidence of their impact was demonstrated, that they
      received adequate technical support for their implementation and their
      monitoring, and that they will be accompanied by strong advocacy among decision
      makers, civil society and beneficiaries. CONCLUSIONS FOR PRACTICE: To conclude,
      for the introduction of new, innovative strategies to reduce micronutrient
      deficiencies in South-East Asia, convincing stakeholders appears to be the first
      hurdle to be taken.

PMID- 30291508
TI  - Nimura lecture: why are you evaluating RV function in patients with pulmonary
      arterial hypertension?
AB  - LV is a pressure-generating pump which endures pressure overload, while RV is a
      flow-generating pump intolerant of pressure overload. Therefore, RV pump function
      (but not RV myocardial contractility) can easily fail in face of severe pulmonary
      arterial hypertension (PH) because of increased afterload. Available indexes of
      RV function are load dependent and incapable of accurately reflecting RV
      myocardial contractility. Animal RV in which myocardium is damaged extensively by
      either soldering iron or coronary occlusion can work well without causing
      systemic congestion or decreased SV. In clinical settings, evaluation of pre
      treatment RV function in patients with PH has limited value in predicting
      prognosis. Furthermore, in virtually all patients with PH after successful lung
      transplantation, RV function has been reported to improve indicating that
      deteriorated RV function in patients with PH is due to an increase in RV
      afterload, but not to decreased RV myocardial contractility. In view of these
      facts, evaluation of RV function seems hardly useful in patients with PH.

PMID- 30291509
TI  - Changes in dynamic mitral valve geometry during percutaneous edge-edge mitral
      valve repair with the MitraClip system.
AB  - BACKGROUND: The aim of this study was to quantify the acute dynamic changes of
      mitral valve (MV) geometry throughout the cardiac cycle-during percutaneous MV
      repair with the MitraClip system by 3-dimensional transesophageal
      echocardiography (3D TEE). METHODS: The MV was imaged throughout the cardiac
      cycle (CC) before and after the MitraClip procedure using 3D TEE in 28 patients
      (mean age, 77 +/- 8 years) with functional mitral regurgitation (FMR). Dynamic
      changes in the MV annulus geometry and anatomical MV orifice area (AMVOA) were
      quantified using a novel semi-automated software. RESULTS: Percutaneous MV repair
      decreased anterior-posterior diameter by up to 9% (at 50% of CC; from 34.5 to
      31.9 mm; p < 0.001) throughout the CC and increased the diastolic lateral-medial
      diameter by up to 7% (at 60% of the CC; from 39.7 to 42.3 mm; p < 0.001), whereas
      the annular circumference and area were not significantly affected. Annulus
      sphericity index was reduced up to 13% (at 50% of the CC; from 0.89 to 0.78, p <
      0.001). The AMVOA also decreased during systole, the maximum decrease being from
      0.6 to 0.2 mm2 (at 0% of CC; p = 0.007), and during diastole the maximum decrease
      being from 4.6 to 1.6 cm2 (at 50% of CC; p < 0.001). CONCLUSIONS: Percutaneous MV
      repair reduces the MR by an improved coaptation of MV leaflets joint with a
      simultaneous indirect reduction of anterior-posterior diameter. Further, the
      MitraClip procedure leads to a reduction of AMVOA of more than 60% during
      diastole.

PMID- 30291507
TI  - Evolution of protein transport to the chloroplast envelope membranes.
AB  - Chloroplasts are descendants of an ancient endosymbiotic cyanobacterium that
      lived inside a eukaryotic cell. They inherited the prokaryotic double membrane
      envelope from cyanobacteria. This envelope contains prokaryotic protein sorting
      machineries including a Sec translocase and relatives of the central component of
      the bacterial outer membrane beta-barrel assembly module. As the endosymbiont was
      integrated with the rest of the cell, the synthesis of most of its proteins
      shifted from the stroma to the host cytosol. This included nearly all the
      envelope proteins identified so far. Consequently, the overall biogenesis of the
      chloroplast envelope must be distinct from cyanobacteria. Envelope proteins
      initially approach their functional locations from the exterior rather than the
      interior. In many cases, they have been shown to use components of the general
      import pathway that also serves the stroma and thylakoids. If the ancient
      prokaryotic protein sorting machineries are still used for chloroplast envelope
      proteins, their activities must have been modified or combined with the general
      import pathway. In this review, we analyze the current knowledge pertaining to
      chloroplast envelope biogenesis and compare this to bacteria.

PMID- 30291510
TI  - Extended mutualism between termites and gut microbes: nutritional symbionts
      contribute to nest hygiene.
AB  - All higher eukaryotes have established symbiotic relationships with diverse
      microorganisms. One of the most well-characterized symbiotic systems is that of
      termites and their intestinal microorganisms, which digest cellulose. Recently,
      diverse types of symbioses between gut microbes and host organisms including
      humans have received growing attention for various features of their complex
      interactions beyond nutrition. In termites, researchers are beginning to explore
      such function of gut symbionts, but only the contribution to internal immunity
      against entomopathogen is known in a few species. Here, we report that gut
      symbionts of the dampwood termite Zootermopsis nevadensis protect nests from the
      spread of the commensal bacterium Serratia marcescens, which has pathogenic
      potential. Defaunated termites dispersed S. marcescens in the surrounding
      environment by feeding on the bacteria, which then survived passage through their
      alimentary tracts, while non-defaunated termites did not. Loss of gut symbionts
      caused a significant reduction in intestinal acetate, which is an important
      carbon source for termites. Culture experiments showed that acetate had
      significant inhibitory effects on S. marcescens at a concentration as low as 12
      mM, which indicated that the intestinal acetate of non-defaunated termites (40
      130 mM) was capable of suppressing this bacterium. These results suggest that
      digestive derivatives produced by intestinal symbionts play an essential role in
      nest hygiene in addition to their nutritional function for termites. Our study
      provides a better understanding of the multifunctionality of symbiotic
      relationships in diverse organisms beyond nutrition.

PMID- 30291511
TI  - CAIX and pax-8 Commonly Immunoreactive in Endolymphatic Sac Tumors: A
      Clinicopathologic Study of 26 Cases with Differential Considerations for
      Metastatic Renal Cell Carcinoma in von Hippel-Lindau Patients.
AB  - Endolymphatic sac tumors (ELSTs) are rare, slowly growing temporal bone neoplasms
      which show a high association with von Hippel-Lindau (VHL) syndrome. The
      immunohistochemistry evaluation of these papillary-cystic neoplasms frequently
      raises the differential diagnosis with renal cell carcinoma, among other
      metastatic neoplasms, whether in VHL patients or not. A cohort of 26 patients
      with ELSTs were evaluated for histologic features, immunohistochemistry findings,
      and association with VHL. Standard immunohistochemistry evaluation was performed.
      Sixteen females and 10 males ranging in age from 10 to 69 years (mean 44; VHL
      mean: 32) at initial presentation, comprised the cohort of patients. Most (86%)
      experienced hearing changes or inner ear symptoms (vertigo, dizziness), with an
      average duration of symptoms for 39 months (range 2-240 months). The tumors were
      an average of 2.9 cm (range 0.4-8 cm), with 14 left, 11 right sided and one
      bilateral tumor. Nine patients had documented VHL, with 3 patients having a
      concurrent or subsequent clear cell renal cell carcinoma. Patients were followed
      an average of 6.2 years (available in 24 patients): 19 alive without disease, 7.5
      years; 2 dead without disease, 1.2 years; and 3 alive with disease, 3.1 years.
      The neoplastic cells show the following immunohistochemistry findings: AE1/AE3,
      EMA, CK7, CAIX, GLUT1, VEGF: 100% of cases tested were positive; pax-8: 85% of
      cases positive; CD10 and RCC: 0% of cases reactive. Based on this cohort of 26
      patients with ELST, 9 of whom had VHL, the strong pax-8 and CAIX should be used
      in conjunction with negative CD10 and RCC to help exclude a metastatic renal cell
      carcinoma. As CAIX is an enzyme overexpressed in hypoxia and hypoxia inducible
      factor is what VHL protein regulates, this is an expected, although previously
      unreported finding. Whether part of VHL or not, VHL mutations may be a somatic
      rather than germline finding in the tumors, a possible further explanation for
      the CAIX reaction.

PMID- 30291512
TI  - Ischemic heart disease in Latin American women current perspective and call to
      action.
AB  - Cardiovascular diseases (CVDs) constitute the main cause of death in Latin
      America (LA), with ischemic heart disease (IHD) as the principal cause in most
      countries. Women are particularly at risk of premature death by CVDs.
      Nevertheless, in LA, as in other parts of the world, there is a misconception at
      public level of the importance of CVDs in women; thus, CVDs do not get as much
      coverage as breast cancer campaigns. Women frequently have atypical symptoms and
      nonobstructive coronary artery disease as well as inequity in medical and
      interventional treatments; therefore, care should be built upon these
      differences. We show the epidemiological situation of IHD in LA women and present
      a strategy to face the problem, considering the control of risk factors, the
      optimized utilization of available resources, and the role of research. The role
      of the International Atomic Energy Agency is highlighted. To adequately face the
      problem of CVD in LA women, a coordinated approach is necessary, involving
      medical professionals, governments, scientific societies, and international
      organizations, as well as the population concerned. In low- and middle-income
      countries, where the best use of available financial and technological resources
      is mandatory, a clinical management combining prevention, guidelines, and
      clinical judgment is required.

PMID- 30291513
TI  - Improvement in hydrogen binding ability of closo-dicarboranes via
      functionalization and designing of extended frameworks.
AB  - Neutral closo-dicarboboranes are reported to have very low H2 binding ability.
      Herein, we report an improvement in H2 binding energy (Eb) of C2B4H6 by
      substituting H atoms with different functional groups like X = F, Cl, Br, and XY
      = BO, CN and NC via quantum-chemical density functional theory based
      computations. In going from B6H62- to C2B4H6, the Eb value is reduced from 14.6
      kJ mol-1 to 2.7 kJ mol-1. C2B4X6 and C2B4(XY)6 systems, which can bind a total of
      eight H2 molecules, with one H2 molecule occupying at each B-B-C face, possess an
      Eb value per H2 in the range of 4.5 kJ mol-1 for X = F, 3.9 kJ mol-1 for X = Cl,
      5.9 kJ mol-1 for X = Br, 6.8 kJ mol-1 for XY = BO, 5.8 kJ mol-1 for XY = CN and
      5.2 kJ mol-1 for XY = NC. The improvement in Eb value is found to be the highest
      in case of C2B4(BO)6, which has the ability to bind 6.6 gravimetric wt% of H2.
      The situation can be made more favorable by applying an external electric field.
      Energy decomposition analysis reveals that although the dispersion interaction
      (ca. 55-65%) has significant role in binding H2 with such types of molecules,
      contribution from electrostatic and orbital interaction is also considerable.
      Further, we modeled an extended system by linking C2B4(BO)n through 'C = C' units
      for H2 storage purpose. The energy difference between the highest occupied and
      the lowest unoccupied molecular orbitals gradually lessens with the increase in
      molecular length. Therefore, it can be tuned gradually by controlling the chain
      length, which may further open up their potency in the field of electronics.
      Graphical abstract C2B4X6 (X = F, Cl, Br) and C2B4(XY)6 (XY = BO, CN, NC) show
      enhanced H2 binding ability from C2B4H6. Further, 1D, 2D and 3-D frameworks can
      be built by joining C2B4(BO)n units via 'C = C' linkage.

PMID- 30291514
TI  - Intravenous thrombolysis for ischemic stroke in the Veneto region: the gap
      between eligibility and reality.
AB  - Intravenous thrombolysis (IVT) is the treatment of choice for most patients with
      acute ischemic stroke. According to the recently updated guidelines, IVT should
      be administered in absence of absolute exclusion criteria. We aimed to assess the
      proportion of ischemic strokes potentially eligible and actually treated with
      IVT, and to explore the reasons for not administering IVT. We prospectively
      collected and analyzed data from 1184 consecutive ischemic stroke patients
      admitted to the 22 Stroke Units (SUs) of the Veneto region from September 18th to
      December 10th 2017. Patients were treated with IVT according to the current
      Italian guidelines. For untreated patients, the reasons for not administering IVT
      were reported by each center in a predefined model including absolute and/or
      relative exclusion criteria and other possible reasons. Out of 841 (71%) patients
      who presented within 4.5 h of stroke onset, 704 (59%) had no other absolute
      exclusion criteria and were therefore potentially eligible for IVT according to
      the current guidelines. However, only 323 (27%) patients were eventually treated
      with IVT. Among 861 (73%) untreated patients, 480 had at least one absolute
      exclusion criterion, 283 only relative exclusion criteria, 56 only other reasons,
      and 42 a combination of relative exclusion criteria and other reasons. Our study
      showed that only 46% (323/704) of the potentially eligible patients were actually
      treated with IVT in the SUs of the Veneto region. All healthcare professionals
      involved in the acute stroke pathway should make an effort to bridge this gap
      between eligibility and reality.

PMID- 30291515
TI  - CKD-MBD: from the Pathogenesis to the Identification and Development of Potential
      Novel Therapeutic Targets.
AB  - PURPOSE OF REVIEW: Although we have seen tremendous advances in the comprehension
      of CKD-MBD pathophysiology during the last few years, this was not accompanied by
      a significant change in mortality rate and quality of life. This review will
      address the traditional and updated pathophysiology of CKD-MBD along with the
      therapeutic limitations that affect CKD-MBD and proposed alternative treatment
      targets. RECENT FINDINGS: An innovative concept brings the osteocyte to the
      center of CKD-MBD pathophysiology, in contrast to the traditional view of the
      skeleton as a target organ for disturbances in calcium, phosphate, parathyroid
      hormone, and vitamin D. Osteocytes, through the synthesis of FGF-23, sclerostin,
      among others, are able to interact with other organs, making bone an endocrine
      organ. Thus, osteocyte dysregulation might be an early event during the course of
      CKD. This review will revisit general concepts on the pathophysiology of CKD-MBD
      and discuss new perspectives for its treatment.

PMID- 30291517
TI  - Toxic Metals and Trace Elements in Artisanal Honeys from the Canary Islands.
AB  - Honey is a natural product made by honey bees from the nectar of flowers or
      secretions produced by other living plant parts. The metal content of the honeys
      is related to the levels of metals in the environment. Due to the importance of
      honey in the human diet and the increase of environmental pollution, it is
      necessary to determine the content of metals in honey to evaluate the
      toxicological risk derived from its consumption. The objective of this study was
      to determine the content of 20 metals (Al, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Li,
      Mg, Mn, Mo, Na, Ni, Pb, Sr, V, and Zn) in different samples of artisanal honey
      from the Canary Islands (Spain) in order to evaluate the dietary intake derived
      from the consumption of these honeys. A total of 161 samples of different types
      of Canary honey were analyzed by ICP-OES (inductively coupled plasma-optical
      emission spectrometry). K (825 mg/kg) was the macroelement found in highest
      concentration, while B (4.25 mg/kg) was the trace element with the highest mean
      concentration. Al (3.33 mg/kg) was the most abundant toxic metal, followed by Pb
      (0.040 mg/kg) and Cd (0.002 mg/kg). A mean consumption of 25 g/day of honey
      mainly contributes to the recommended daily intake of Cu (1.34% adults) and K
      (0.67% adults). As regards the toxic metals, the contribution percentage to the
      TDI (tolerable daily intake) of Pb at 2.92% for adults is noteworthy. However,
      the consumption of honey does not imply a high intake of metals and, therefore,
      does pose a risk to the health of adult men and women.

PMID- 30291518
TI  - Effect of Fe and Cd Co-Exposure on Testicular Steroid Metabolism, Morphometry,
      and Spermatogenesis in Mice.
AB  - The mechanism of testicular toxicity of simultaneous multiple exposures to metals
      is poorly understood. Previous studies reported that the toxic effect of cadmium
      (Cd) is modified by tissue concentration of iron (Fe). Using the mice (Mus
      musculus) model in the present study, we demonstrated that combined Cd (25 mg kg
      1 bw) and Fe (100 mg kg-1 bw) treatment increased both Cd and Fe testicular
      concentrations much more than separate exposures to either of the metals.
      Intratesticular Cd and Fe concentrations were inversely correlated (r = - 0.731,
      p < 0.05) on administration of Fe but not on combined exposure to both metals
      when they were positively correlated (versus Cd; r = 0.793, versus Fe; r = 0.779,
      p < 0.05). Additionally, Cd + Fe treatment increased testicular lipid
      peroxidation and depleted intratestesticular testosterone, cholesterol and
      glutathione concentrations much more than their separate treatment. This was also
      associated with decreased activity of the germ cell marker, testicular lactate
      dehydrogenase, and increased testicular myeloperoxidase activity. These changes
      resulted in decreased seminiferous epithelial height, tubular diameter, germ cell
      (spermatogonia, spermatocytes, and spermatids) numbers, and severe tissue damage.
      In conclusion, Cd + Fe intake have synergistic toxic effects on testicular
      steroid formation and spermatogenesis due to the high testicular concentrations
      of both metals.

PMID- 30291516
TI  - Obesity and Pulmonary Hypertension.
AB  - PURPOSE OF REVIEW: Whether the present obesity epidemic will increase the
      prevalence of pulmonary hypertension over the next decades is unclear. We review
      the obesity-related mechanisms that may further the development and progression
      of pulmonary hypertension. RECENT FINDINGS: Systemic and local inflammation,
      insulin resistance and oxidative stress contribute to the pathobiology of obesity
      and pulmonary arterial hypertension. Preliminary data suggest that expansion of
      adipose tissue surrounding the pulmonary artery may hasten the progression of
      pulmonary arterial hypertension in obese persons. Further, obesity-associated
      cardiac and pulmonary conditions may increase the prevalence of groups 2 and 3
      pulmonary hypertension. The obesity epidemic is likely to increase the prevalence
      of pulmonary arterial hypertension by enabling vascular remodeling. Obesity
      associated cardiac and pulmonary conditions will increase pulmonary hypertension
      prevalence.

PMID- 30291519
TI  - Macrophage polarization as a novel weapon in conditioning tumor microenvironment
      for bladder cancer: can we turn demons into gods?
AB  - Macrophages are major components of the immune infiltration in cancer where they
      can affect tumor behavior. In the bladder, they play important roles during the
      resolution of infectious processes and they have been associated with a worse
      clinical prognosis in bladder cancer. The present review focused on the
      characteristics of these important immune cells, not only eliciting an innate
      immune surveillance, but also on their importance during the cancer immunoediting
      process. We further discuss the potential of targeting macrophages for anticancer
      therapy, the current strategies and the state of the art as well as the foreseen
      role on combined therapies on the near future. This review shows how a
      comprehensive understanding of macrophages within the tumor should translate to
      better clinical outcome and new therapeutic strategies focusing especially on
      bladder cancer.

PMID- 30291520
TI  - World Society for Pediatric Infectious Diseases declaration on combating
      antimicrobial resistance in children.

PMID- 30291522
TI  - Monographic issue of the italian society for shoulder and elbow surgery.

PMID- 30291521
TI  - Unique Populations with Episodic Migraine: Pregnant and Lactating Women.
AB  - PURPOSE OF REVIEW: Migraine is a disabling and prevalent neurological disease,
      commonly affecting women during their reproductive years. It is crucial for
      providers to be able to adequately counsel women who are pregnant, planning
      pregnancy, or nursing, regarding preventive and abortive treatment options for
      episodic migraine. This review will discuss (1) the expected course of migraine
      during pregnancy and the post-partum period, (2) recommended preventive therapies
      for migraine during pregnancy and lactation, and (3) recommended abortive
      medications for migraine during pregnancy and lactation. RECENT FINDINGS: Recent
      research has indicated safety for triptan use during pregnancy and ibuprofen use
      during the first trimester of pregnancy. Considerations for use of emerging
      migraine-preventive treatment, such as non-invasive neurostimulators, are
      discussed. For clinical decision-making and patient counseling, it is important
      to understand both the limitations in determining teratogenic effects in humans
      and the principles affecting medication transmission from mother to breast milk.

PMID- 30291523
TI  - Effects of pseudoephedrine on parameters affecting exercise performance: a meta
      analysis.
AB  - BACKGROUND: Pseudoephedrine (PSE), a sympathomimetic drug, commonly used in nasal
      decongestants, is currently banned in sports by the World Anti-Doping Agency
      (WADA), as its stimulant activity is claimed to enhance performance. This meta
      analysis described the effects of PSE on factors relating to sport performance.
      METHODS: All included studies were randomised placebo-controlled trials and were
      conducted in a double blind crossover fashion. All participants (males and
      females) were deemed to be healthy. For the primary analysis, standardised mean
      difference effect sizes (ES) were calculated for heart rate (HR), time trial (TT)
      performance, rating of perceived exertion, blood glucose, and blood lactate.
      RESULTS: Across all parameters, effects were trivial with the exception of HR,
      which showed a small positive increase in favour of PSE ingestion (ES = 0.43; 95%
      confidence interval: - 0.01 to 0.88). However, subgroup analyses revealed
      important trends. Effect sizes for HR (increase) and TT (quicker) were larger in
      well-trained (VO2 max (maximal oxygen consumption) >= 65 ml/kg/min) and younger
      (< 28 years) participants, for shorter (< 25 mins) bouts of exercise and when PSE
      was administered less than 90 min prior to performance. There was evidence of a
      dose-response effect for TT and HR with larger doses (> 170 mg) resulting in
      small (ES = - 0.24) and moderate (ES = 0.85) effect sizes respectively for these
      variables. CONCLUSIONS: We conclude, however, that the performance benefit of
      pseudoephedrine is marginal and likely to be less than that obtained from
      permitted stimulants such as caffeine.

PMID- 30291524
TI  - Evaluation of silicon membranes for extracorporeal membrane oxygenation (ECMO).
AB  - While extracorporeal membrane oxygenation (ECMO) is a valuable therapy for
      patients with lung or heart failure, clinical use of ECMO remains limited due to
      hemocompatibility concerns with pro-coagulatory hollow fiber membrane geometries.
      Previously, we demonstrated the feasibility of silicon nanopore (SNM) and
      micropore (SMUM) membranes for transport between two liquid-phase compartments in
      blood-contacting devices. Herein, we investigate various pore sizes of SNM and
      SMUM membranes - alone or with a polydimethylsiloxane (PDMS) protective coating -
      for parameters that determine suitability for gas exchange. We characterized the
      bubble or rupture point of these membranes to determine sweep gas pressures at
      which gas emboli would form. The smallest pore size SNM and the SMUM with PDMS
      coating could be pressurized in excess of 260 cmHg without rupture, which is
      comparable to hollow fiber sweep gas pressures. Oxygen flux for the SMUM with and
      without PDMS was insignificantly different at 0.0306 +/- 0.0028 and 0.0297 +/-
      0.0012 mL/min, respectively, while SNM flux was significantly lower at 0.0149 +/-
      0.0040 mL/min. However, the area-normalized mass transfer coefficient of the SNM
      was 338 +/- 54 mL O2 m-2 min-1 cmHg-1 - an order of magnitude higher than that of
      the SMUM with and without PDMS (57.3 +/- 5.5 and 55.6 +/- 2.2 mL O2 m-2 min-1
      cmHg-1). Ultimately, we conclude that SMUM-PDMS may make effective membranes for
      ECMO, since they are both mechanically robust and capable of high oxygen flux.

PMID- 30291525
TI  - The European Diploma in Radiology (EDiR): investing in the future of the new
      generations of radiologists.
AB  - This review aims to describe the organisation and the content of the European
      Diploma in Radiology (EDiR). The EDiR examination is available to radiologists
      and radiology residents in their last year of training. It certifies that their
      levels of knowledge and competency are in line with the ESR European Training
      Curriculum for Radiology (ETC) of the European Society of Radiology (ESR). The
      EDiR is an additional qualification of excellence, which serves the
      standardisation and accreditation of radiologists across European borders. It
      provides an international benchmark for general radiology and is officially and
      fully endorsed by the European Union of Medical Specialists (UEMS) and the ESR.
      The EDiR is recognised as an equivalent of the Polish exit training examination,
      the first part of the Turkish board examination and the image interpretation part
      of the Finnish national examination. Moreover, in order to practice radiology in
      The Netherlands, trainees must either pass their national board examination or
      the EDiR. It has significant value in many other countries. The examination
      consists of three parts: Multiple Response Questions (MRQs), Short Cases (SCs)
      and the Clinically Oriented Reasoning Evaluation (CORE). The committees that form
      the EDiR Scientific Board follow a structured workflow to prepare each
      examination, ensuring an adequate peer review system for quality assurance. KEY
      POINTS: * EDiR helps to standardise radiology training. * EDiR is an
      international certification method established across Europe. * Ideally all
      training programmes should embrace EDiR as exit examination after completing
      their training period. * The EDiR exam consists of multiple response questions,
      short cases and the Clinically Oriented Reasoning Evaluation.

PMID- 30291528
TI  - Linkage of the UK Clinical Practice Research Datalink with the national cancer
      registry.

PMID- 30291527
TI  - Which is the proper reference tissue for measuring the change in FDG PET
      metabolic volume of cardiac sarcoidosis before and after steroid therapy?
AB  - BACKGROUND: Cardiac sarcoidosis (CS) is a rare but potentially life-threatening
      disease that causes conduction disturbance, systolic dysfunction, and, most
      notably, sudden cardiac death. 18F-fluorodeoxyglucose (FDG) positron emission
      tomography/computed tomography (PET/CT) plays important roles not only in
      diagnosing CS but also in evaluating the effects of anti-inflammatory therapy. A
      volume-based analysis of parameters measured by FDG PET, so-called cardiac
      metabolic volume (CMV), has emerged as a new assessment tool. CMV is measured as
      the volume within the boundary determined by a reference tissue such as the liver
      and the blood pool uptake. However, there is a possibility that oral steroid
      therapy could lead to variations of the liver and the blood pool uptake. Here, we
      attempted to evaluate the steroid effects on the liver and the blood pool uptake.
      A total of 38 CS patients who underwent FDG PET/CT before and during steroid
      therapy were retrospectively enrolled. Volumes of interest (VOIs) were placed in
      the right lobe of the liver and descending aorta (DA). The maximum standardized
      uptake value (SUVmax), SUVmean, and SUVpeak of the liver and DA were compared
      between time points before and during steroid therapy. RESULTS: The SUVmax,
      SUVmean, and SUVpeak of the liver during steroid therapy significantly increased
      from the time point before the therapy (SUVmax 3.5 +/- 0.4 vs. 3.8 +/- 0.6, p =
      0.014; SUVmean 2.7 +/- 0.3 vs. 3.0 +/- 0.5, p = 0.0065; SUVpeak 3.0 +/- 0.4 vs.
      3.4 +/- 0.6, p = 0.006). However, the SUVmax, SUVmean, and SUVpeak in the DA did
      not significantly change (SUVmax 2.2 +/- 0.3 vs. 2.2 +/- 0.4, p = 0.46; SUVmean
      1.9 +/- 0.3 vs. 2.0 +/- 0.4, p = 0.56; SUVpeak 2.0 +/- 0.3 vs. 2.0 +/- 0.3, p =
      0.70). CONCLUSIONS: We measured FDG uptake in the liver and blood pool before and
      during steroid therapy. Steroid therapy increased the liver uptake but not the
      blood pool uptake. Our findings suggested that the DA uptake is a more suitable
      threshold than liver uptake to evaluate therapeutic effects using volume-based
      analysis of cardiac FDG PET.

PMID- 30291526
TI  - Novel Imaging Biomarkers for Huntington's Disease and Other Hereditary Choreas.
AB  - PURPOSE OF THE REVIEW: Imaging biomarkers for neurodegenerative disorders are
      primarily developed with the goal to aid diagnosis, to monitor disease
      progression, and to assess the efficacy of disease-modifying therapies in support
      to clinical outcomes that may either show limited sensitivity or need extended
      time for their evaluation. This article will review the most recent concepts and
      findings in the field of neuroimaging applied to Huntington's disease and
      Huntington-like syndromes. Emphasis will be given to the discussion of potential
      pharmacodynamic biomarkers for clinical trials in Huntington's disease (HD) and
      of neuroimaging tools that can be used as diagnostic biomarkers in HD-like
      syndromes. RECENT FINDINGS: Several magnetic resonance (MR) and positron emission
      tomography (PET) molecular imaging tools have been identified as potential
      pharmacodynamic biomarkers and others are in the pipeline after preclinical
      validation. MRI and 18F-fluorodeoxyglucose PET can be considered useful
      supportive diagnostic tools for the differentiation of other HD-like syndromes.
      New trials in HD have the primary goal to lower mutant huntingtin (mHTT) protein
      levels in the brain in order to reduce or alter the progression of the disease.
      MR and PET molecular imaging markers have been developed as tools to monitor
      disease progression and to evaluate treatment outcomes of disease-modifying
      trials in HD. These markers could be used alone or in combination for detecting
      structural and pharmacodynamic changes potentially associated with the lowering
      of mHTT.

PMID- 30291529
TI  - Apgar score and risk of autism.
AB  - Low Apgar score has been associated with higher risk for several neurological and
      psychiatric disorders, including cerebral palsy and intellectual disability.
      Studies of the association between Apgar score and autism spectrum disorder (ASD)
      have been inconsistent. We aimed to investigate (1) the association between low
      Apgar score at 5 min and risk for ASD, and (2) the modifying effects of
      gestational age and sex on this association in the largest multinational database
      of ASD. We included prospective data from 5.5 million individuals and over 33,000
      cases of ASD from Norway, Sweden, Denmark and Western Australia who were born
      between 1984 and 2007. We calculated crude and adjusted risk ratios (RR) with 95%
      confidence intervals (95% CIs) for the associations between low Apgar score and
      ASD. All analyses for ASD were repeated for autistic disorder (AD). We used
      interaction terms and stratified analysis to investigate the effects of sex,
      gestational age, and birth weight on the association. In fully adjusted models,
      low Apgar scores (1-3) (RR, 1.42; 95% CI, 1.16-1.74), and intermediate Apgar
      scores (4-6) (RR, 1.50; 95% CI, 1.36-1.65) were associated with a higher RR of
      ASD than optimal Apgar score (7-10). The point estimates for low (RR, 1.88; 95%
      CI, 1.41-2.51) and intermediate Apgar score (RR, 1.54; 95% CI, 1.32-1.81) were
      larger for AD than for ASD. This study suggests that low Apgar score is
      associated with higher risk of ASD, and in particular AD. We did not observe any
      major modifying effects of gestational age and sex, although there seems to be
      substantial confounding by gestational age and birth weight on the observed
      association.

PMID- 30291530
TI  - Massive citations to misleading methods and research tools: Matthew effect,
      quotation error and citation copying.

PMID- 30291531
TI  - Does Religion Predict Health-Promoting Behaviors in Community-Dwelling Elderly
      People?
AB  - As the aging phenomenon gains importance in many societies, regular health
      promoting activities by the elderlies become more crucial for disability
      reduction and their health promotion. Religious viewpoints and perspectives can
      have an influence on the individuals' assessment of life events. Recent studies
      show a correlation between religiosity and mental health. However, there is
      limited number of studies on the relationship between religiosity and health
      behaviors, especially in elderly. The purpose of this research is to evaluate
      religion's predictive power in health-improving behaviors of the elderly. This
      cross-sectional study was conducted on 316 community-dwelling elderly with the
      mean age of 67.9 +/- 6.6 years, who were functionally independent without
      cognitive or mental impairments. Health-promoting lifestyle profile 2 assessment
      (HPLP2) and Alport questionnaires were used to assess health behaviors and
      religious orientation, respectively. Data analysis was performed by independent T
      test and multiple linear regression models with SPSS version 23. An internal
      religious orientation was found in 71 elderly; this accounts for 22.5% of the
      study population. Based on the health behavior scoring 154 individuals, 48.8% of
      the study population obtained a score of higher or equal to 139. These
      individuals were placed on third quartile and higher. Among the health behavior
      components, "the health responsibility" was the only component related to
      religious orientation [internal 25.1 +/- 6.6 (P < 0.001, r = 0.78) vs. external
      22.6 +/- 6.5 (P > 0.05, r = 0.22)]. Based on the multiple linear regression
      models, no significant relationship was found between total health behavior score
      and religious orientation. However, a significant relationship existed between
      the participants' health behaviors and some of their profile. The results
      indicate that despite good health behaviors in nearly half of the elderlies, no
      significant relationship was found between health behavior and religious
      orientation. The results suggest possible impact of other religion-related
      concepts including private religious behaviors, devotion, spiritual
      transcendence, religious adaptation, and religious traditions and experiences on
      the health behaviors. These concepts require further study for better
      understanding of their impact.

PMID- 30291532
TI  - Investigating the Effect of Religious Intervention on Mental Vitality and Sense
      of Loneliness Among the Elderly Referring to Community Healthcare Centers.
AB  - The growth of elderly population is among the most important issues in the world,
      and religious interventions can help them to keep their health. For this reason,
      this study was conducted with the aim of determining the effect of religious
      intervention on subjective vitality and sense of loneliness of the elderly
      referring to healthcare centers. This semi-experimental study was conducted on 88
      elderlies referring to community healthcare centers of Ilam City. The elderlies
      were randomly assigned into test and control groups, and subjective vitality and
      sense of loneliness questionnaire was distributed to them. For the elderly in the
      test group, twelve 30-45-min sessions of religious intervention were held. Then,
      at intervals of immediately, 1 month, and 2 months after the study, the studied
      questionnaires were redistributed again among the elderly, and the data were
      analyzed using SPSS 16 and through descriptive statistics as well as repeated
      measures of analysis of variance. Before intervention, there was no difference
      between mental vitality and fear of loneliness in the elderly, but after
      intervention, the amount of mental vitality increased and fear of loneliness
      decreased. Since in this study, implementation of religious intervention resulted
      in improved subjective vitality and diminished sense of loneliness among the
      elderly, it is suggested that this effective intervention be also used in other
      studies.

PMID- 30291533
TI  - Religiously/Spiritually Involved, but in Doubt or Disbelief-Why? Healthy?
AB  - The question of why atheists and agnostic theists attend religious services and
      pray (and what that might mean for their health) is examined through (1) a
      thematic analysis of commentaries, perspective pieces, and news articles from the
      popular literature, and (2) a critical review of scholarly research involving
      comparisons between religious and nonreligious individuals on a variety of health
      related outcomes. Findings suggest that atheists and agnostic theists can take
      pleasure in attending religious services, and they may be driven to pray at
      times. In many cases, this was explained by their efforts to stay connected and
      avoid or manage conflict with family members. Despite a pattern of friction
      between nonbelievers and believers across the dataset, they predominantly agreed
      on the whys and wherefores of religious service attendance and the prospect that
      congregants could "bridge the worlds of belief and nonbelief." The themes
      identified are intended to inform the development of qualitative interview
      protocols and survey instruments. Although health was not among the most salient
      themes in the narratives analyzed here, many of the reasons cited for religious
      service attendance and prayer can be tied to existing literature that has
      relevance for health. Atheists who experience dissonance between their self
      perception and nonbelief in God-and agnostic theists who are prone to existential
      uncertainty and have only moderate faith-might experience poorer health outcomes.
      Recommendations focus on the need to (a) supplement secondary analyses of
      archival survey data with qualitative descriptions of belief systems within
      groups, and (b) move away from the adversarial stance taken by some of the
      authors of recently published studies on atheism, nonreligion, and health.

PMID- 30291534
TI  - Structural basis of the nonribosomal codes for nonproteinogenic amino acid
      selective adenylation enzymes in the biosynthesis of natural products.
AB  - Nonproteinogenic amino acids are the unique building blocks of nonribosomal
      peptides (NRPs) and hybrid nonribosomal peptide-polyketides (NRP-PKs) and
      contribute to their diversity of chemical structures and biological activities.
      In the biosynthesis of NRPs and NRP-PKs, adenylation enzymes select and activate
      an amino acid substrate as an aminoacyl adenylate, which reacts with the thiol of
      the holo form of the carrier protein to afford an aminoacyl thioester as the
      electrophile for the condensation reaction. Therefore, the substrate specificity
      of adenylation enzymes is a key determinant of the structure of NRPs and NRP-PKs.
      Here, we focus on nonproteinogenic amino acid selective adenylation enzymes,
      because understanding their unique selection mechanisms will lead to accurate
      functional predictions and protein engineering toward the rational biosynthesis
      of designed molecules containing amino acids. Based on recent progress in the
      structural analysis of adenylation enzymes, we discuss the nonribosomal codes of
      nonproteinogenic amino acid selective adenylation enzymes.

PMID- 30291536
TI  - Differences in Stability, Activity and Mutation Effects Between Human and Mouse
      Leucine-Rich Repeat Kinase 2.
AB  - Mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene have been implicated
      in the pathogenesis of Parkinson's disease (PD). Identification of PD-associated
      LRRK2 mutations has led to the development of novel animal models, primarily in
      mice. However, the characteristics of human LRRK2 and mouse Lrrk2 protein have
      not previously been directly compared. Here we show that proteins from different
      species have different biochemical properties, with the mouse protein being more
      stable but having significantly lower kinase activity compared to the human
      orthologue. In examining the effects of PD-associated mutations and risk factors
      on protein function, we found that conserved substitutions such as G2019S affect
      human and mouse LRRK2 proteins similarly, but variation around position 2385,
      which is not fully conserved between humans and mice, induces divergent in vitro
      behavior. Overall our results indicate that structural differences between human
      and mouse LRRK2 are likely responsible for the different properties we have
      observed for these two species of LRRK2 protein. These results have implications
      for disease modelling of LRRK2 mutations in mice and on the testing of
      pharmacological therapies in animals.

PMID- 30291535
TI  - Association of ERG/PTEN status with biochemical recurrence after radical
      prostatectomy for clinically localized prostate cancer.
AB  - We have previously demonstrated a significant correlative relationship between
      PTEN deletion and ERG rearrangement, both in the development of clinically
      localized prostate cancers and metastases. Herein, we evaluate the cooperative
      role of ERG and PTEN in oncological outcomes after radical prostatectomy for
      clinically localized prostate cancer. We evaluated ERG and PTEN status using
      three previously described cohorts. The first cohort included 235 clinically
      localized prostate cancer cases represented on tissue microarrays (TMA),
      evaluated using previously validated FISH assays for ERG and PTEN. The second
      cohort included 167 cases of clinically localized prostate cancer on TMAs
      evaluated for PTEN by FISH, and for PTEN and ERG by dual IHC. The third cohort
      comprised 59 clinically localized prostate cancer cases assessed by array
      comparative genomic hybridization (aCGH). Kaplan-Meir plots and long rank tests
      were used to assess the association of ERG and PTEN status with biochemical
      recurrence after radical prostatectomy for clinically localized prostate cancer.
      Of the 317 cases eligible for analyses with evaluable ERG and PTEN status, 88
      (27.8%) patients developed biochemical recurrence over a median follow-up of 5.7
      years. Overall, 45% (142/317) of cases demonstrated ERG rearrangement and 20%
      (62/317) of cases demonstrated PTEN loss. Hemizygous and homozygous deletion of
      PTEN was seen in 10% (18/175) and 3% (5/175) of ERG-negative cases, respectively.
      In contrast, hemizygous and homozygous deletion of PTEN was seen in 11% (15/142)
      and 17% (24/123) of ERG-positive cases, respectively. PTEN loss (heterozygous or
      homozygous) was significantly associated with shorter time to biochemical
      recurrence compared to no PTEN loss (p < 0.001). However, ERG rearrangement
      versus no rearrangement was not associated with time to PSA recurrence (p =
      0.15). Patients who exhibited ERG rearrangement and loss of PTEN had no
      significant difference in time to recurrence compared to patients with wild-type
      ERG and loss of PTEN (p = 0.30). Our findings confirm a mutual cooperative role
      of ERG and PTEN in the pathogenesis of prostate cancer, particularly for
      homozygous PTEN deletion. ERG did not stratify outcome either alone or in
      combination with PTEN in this cohort.

PMID- 30291537
TI  - Distinct Cytokine and Chemokine Expression in Plasma and Calpeptin-Treated PBMCs
      of a Relapsing-Remitting Multiple Sclerosis Patient: A Case Report.
AB  - The cytokine/chemokine expression signature of a 60-year-old African American
      male with relapsing-remitting multiple sclerosis (RRMS) was analyzed using
      patient blood samples obtained from two separate visits to the clinic. Thirty-six
      different cytokines, chemokines, and growth factors were detected in the plasma
      of the RRMS patient using a multiplexed bead-based immunoassay. Results indicated
      that at least ten of these factors with a concentration of > 100 pg/mL are
      identified as pro-inflammatory. Calpain inhibition led to an anti-inflammatory
      effect, as indicated by a decrease in expression of pro-inflammatory
      cytokines/chemokines such as GM-CSF, IFNgamma, and IL-17A, and a relative
      increase in two of the anti-inflammatory cytokines (IL-13 and IL-4) in the
      peripheral blood mononuclear cells activated with anti-CD3/CD28. Overall, these
      results suggest that the unique cytokine/chemokine pattern observed in the plasma
      of the RRMS patient can be used as a prognostic marker and calpain inhibition may
      be used as a novel therapeutic strategy for treating excessive inflammatory
      response specific to RRMS patients.

PMID- 30291539
TI  - Cerebral arterial time constant calculated from the middle and posterior cerebral
      arteries in healthy subjects.
AB  - The cerebral arterial blood volume changes (?CaBV) during a single cardiac cycle
      can be estimated using transcranial Doppler ultrasonography (TCD) by assuming
      pulsatile blood inflow, constant, and pulsatile flow forward from large cerebral
      arteries to resistive arterioles [continuous flow forward (CFF) and pulsatile
      flow forward (PFF)]. In this way, two alternative methods of cerebral arterial
      compliance (Ca) estimation are possible. Recently, we proposed a TCD-derived
      index, named the time constant of the cerebral arterial bed (tau), which is a
      product of Ca and cerebrovascular resistance and is independent of the diameter
      of the insonated vessel. In this study, we aim to examine whether the tau
      estimated by either the CFF or the PFF model differs when calculated from the
      middle cerebral artery (MCA) and the posterior cerebral artery (PCA). The
      arterial blood pressure and TCD cerebral blood flow velocity (CBFVa) in the MCA
      and in the PCA were non-invasively measured in 32 young, healthy volunteers
      (median age: 24, minimum age: 18, maximum age: 31). The tau was calculated using
      both the PFF and CFF models from the MCA and the PCA and compared using a non
      parametric Wilcoxon signed-rank test. Results are presented as medians (25th-75th
      percentiles). The cerebrovascular time constant estimated in both arteries using
      the PFF model was shorter than when using the CFF model (ms): [64.83 (41.22
      104.93) vs. 178.60 (160.40-216.70), p < 0.001 in the MCA, and 44.04 (17.15-81.17)
      vs. 183.50 (153.65-204.10), p < 0.001 in the PCA, respectively]. The tau obtained
      using the PFF model was significantly longer from the MCA than from the PCA, p =
      0.004. No difference was found in the tau when calculated using the CFF model.
      Longer tau from the MCA might be related to the higher Ca of the MCA than that of
      the PCA. Our results demonstrate MCA-PCA differences in the tau, but only when
      the PFF model was applied.

PMID- 30291538
TI  - Evaluation of expressive writing for postpartum health: a randomised controlled
      trial.
AB  - Pregnancy, birth and adjusting to a new baby is a potentially stressful time that
      can negatively affect the health of women. There is some evidence that expressive
      writing can have positive effects on psychological and physical health,
      particularly during stressful periods. The current study aimed to evaluate
      whether expressive writing would improve women's postpartum health. A randomized
      controlled trial was conducted with three conditions: expressive writing (n =
      188), a control writing task (n = 213), or normal care (n = 163). Measures of
      psychological health, physical health and quality of life were measured at
      baseline (6-12 weeks postpartum), 1 and 6 months later. Ratings of stress were
      taken before and after the expressive writing task. Intent-to-treat analyses
      showed no significant differences between women in the expressive writing,
      control writing and normal care groups on measures of physical health, anxiety,
      depression, mood or quality of life at 1 and 6 months. Uptake and adherence to
      the writing tasks was low. However, women in the expressive writing group rated
      their stress as significantly reduced after completing the task. Cost analysis
      suggest women who did expressive writing had the lowest costs in terms of
      healthcare service use and lowest cost per unit of improvement in quality of
      life. Results suggest expressive writing is not effective as a universal
      intervention for all women 6-12 weeks postpartum. Future research should examine
      expressive writing as a targeted intervention for women in high-risk groups, such
      as those with mild or moderate depression, and further examine cost
      effectiveness.Clinical trial registration number ISRCTN58399513 www.isrctn.com.

PMID- 30291540
TI  - Service Coordination by Public Sector Managers in a Human Service Contracting
      Environment.
AB  - Despite emerging evidence of contracting for evidence-based practices (EBP),
      little research has studied how managers lead contract-based human service
      delivery. A 2015 survey of 193 managers from five San Francisco Bay Area county
      human service departments examined the relationship between contract-based
      service coordination (i.e., structuring cross-sector services, coordinating
      client referrals and eligibility, overseeing EBP implementation) and the
      predictors of managerial role, involvement, and boundary spanning. Multivariate
      regression results suggested that county managers identified fewer service
      coordination challenges if they were at the executive and program levels, had
      greater contract involvement, and engaged in contract-focused boundary spanning.
      In conclusion, we underscore the organizational and managerial dimensions of
      contract-based service delivery.

PMID- 30291541
TI  - Four new species of dactylogyrids (Monogenea: Dactylogyridae) parasitic on gills
      of labrid and sparid fishes from Southeastern Pacific Ocean off Peru.
AB  - During a research on gill ectoparasites of Peruvian marine fishes, four
      dactylogyrid (Monogenea) species, parasitising two teleost species, Bodianus
      diplotaenia (Gill) (Labridae) and Calamus brachysomus (Lockington) (Sparidae),
      were found. Euryhaliotrema luisae n. sp. ex C. brachysomus is differentiated from
      other congeneric species by the morphology of the male copulatory organ, which
      comprises a coil of nine counterclockwise rings, and by the morphology of the
      anchors and bars. Euryhaliotrema magnopharyngis n. sp. ex C. brachysomus can be
      distinguished from all other congeners by having a well-developed pharynx
      occupying much of the anterior region and by the ventral bar, which is V-shaped,
      with well-elongated, thin arms. In addition, E. luisae n. sp. and E.
      magnopharyngis n. sp. can be differentiated from all other members of
      Euryhaliotrema Kritsky & Boeger, 2002 by the presence of a glandular oval plate
      lying on peduncle. Haliotrema diplotaenia n. sp. ex B. diplotaenia is
      characterised by the structure of the male copulatory organ, comprising a tapered
      shaped cirrus tube with twisted acute tip and a filament-shaped accessory piece
      with medial and distal expansions, and by the morphology of the ventral bar
      (inverted W-shaped, with short lateral ends and two anterior conical
      protuberances). Haliotrema saezae n. sp. ex B. diplotaenia differs from all other
      members of Haliotrema Johnston & Tiegs, 1922 by having a tubular copulatory organ
      with curved distal tip and a filament-shaped accessory piece without lateral
      expansions, and by the morphology of anchors and bars. The present findings are
      added to the other six marine dactylogyrids previously reported from Peru.

PMID- 30291542
TI  - Perioperative intervention by oral medicine team in cardiovascular surgery
      patients.
AB  - In brief, perioperative oral intervention consists of elimination of odontogenic
      foci and maintenance of oral hygiene in patients undergoing surgery. The
      importance of oral intervention before, during, and after medical treatments is
      well-known, especially in cancer patients, because odontogenic foci such as
      untreated deep dental caries or periodontitis can cause systemic infection in
      patients with myelosuppression resulting from chemotherapy. Although
      perioperative oral intervention is currently recommended for patients with
      cardiovascular disease, its efficacy in this population has not been established.
      This article consists of three sections: first, we review the current knowledge
      about the association between dental disease and cardiovascular disease to show
      the importance of oral hygiene maintenance and the risks of invasive dental
      procedures in patients with cardiovascular disease; second, we introduce
      pertinent, but limited evidence concerning the effect of oral care in preventing
      postoperative pneumonia; and finally, we present the optimal strategy for
      perioperative oral intervention in cardiovascular surgery patients.

PMID- 30291543
TI  - Lipomers (Lipid-polymer Hybrid Particles) of Vardenafil Hydrochloride: a
      Promising Dual Platform for Modifying the Drug Release Rate and Enhancing Its
      Oral Bioavailability.
AB  - Vardenafil hydrochloride is commonly used for the curing of erectile dysfunction.
      VAR suffers certain limitations: (i) short elimination half-life (4-5 h), (ii)
      low aqueous solubility (0.11 mg/mL), (iii) susceptibility to extensive first-pass
      metabolism and drug efflux transporters (P-glycoprotein), and (iv) limited (15%)
      oral bioavailability. The current study focused on the development of VAR
      lipomers as promising modified release systems able to enhance oral
      bioavailability. VAR-lipomers (lipid-polymer complexes) were successfully
      developed by a modified precipitation technique employing a lipid (polyglyceryl-6
      distearate or glyceryl tristearate) and an amphiphilic polymer (Gantrez(r)).
      Three VAR:lipid ratios [1:1, 1:2, and 1:3] and three VAR:Gantrez(r) ratios [4:1,
      2:1, and 1:1] were investigated. Solid-state characterization studies involved
      differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier
      transform infrared (FT-IR) spectroscopy. The systems were assessed for particle
      size, polydispersity index (PDI), zeta-potential, VAR entrapment-efficiency
      (EE%), morphology, and VAR released % after 2 h (Q2h) and 8 h (Q8h). The best
      achieved system (the highest desirability) was promoted for pharmacokinetic
      studies in fasted rabbits. Statistical analysis of data revealed that L9 system
      (PGDS, VAR, and Gantrez(r); 3:1:1, respectively) had the highest desirability
      (0.85) with respect to spherical particle size (622.15 nm), PDI (0.11), zeta
      potential (-27.90 mV), EE% (62.80%), Q2h (43.45%), and Q8h (77.40%). With respect
      to Levitra(r) tablets, the significantly higher relative bioavailability (170%),
      delayed Tmax, and extended MRT(0-infinity) clarified the dual ability of L9
      system. Lipomers are emerging systems capable of modifying the rate of VAR
      release and promoting its oral bioavailability.

PMID- 30291544
TI  - Radiolabeling of Preformed Niosomes with [99mTc]: In Vitro Stability,
      Biodistribution, and In Vivo Performance.
AB  - Nanocarriers radiolabeled with [99mTc] can be used for diagnostic imaging and
      radionuclide therapy, as well as tracking their pharmacokinetic and
      biodistribution characteristics. Due to the advantages of niosomes as an ideal
      drug delivery system, in this study, the radiolabeling procedure of niosomes by
      [99mTc]-HMPAO complexes was investigated and optimized. Glutathione (GSH)-loaded
      niosomes were prepared using a thin-film hydration method. To label the niosomes
      with [99mTc], the preformed GSH-loaded niosomes were incubated with the [99mTc]
      HMPAO complex and were characterized for particle size, size distribution, zeta
      potential, morphology, and radiolabeling efficiency (RE). The effects of GSH
      concentration, incubation time, incubation temperature, and niosomal composition
      on RE were investigated. The biodistribution profile and in vivo SPECT/CT imaging
      of the niosomes and free [99mTc]-HMPAO were also studied. Based on the results,
      all vesicles had nano-sized structure (160-235 nm) and negative surface charge.
      Among the different experimental conditions that were tested, including various
      incubation times, incubation temperatures, and GSH concentrations, the optimum
      condition that resulted in a RE of 92% was 200-mM GSH and 15-min incubation at 40
      degrees C. The in vitro release study in plasma showed that about 20% of
      radioactivity was released after 24 h, indicating an acceptable radiolabeling
      stability in plasma. The biodistribution of niosomes was clearly different from
      the free radiolabel. Niosomes carrying radionuclide were successfully used for
      tracking the in vivo disposition of these carriers and SPECT/CT imaging in rats.
      Furthermore, biodistribution studies in tumor-bearing mice revealed higher tumor
      accumulation of the niosomal formulation as compared with [99mTc]-HMPAO.

PMID- 30291545
TI  - The effect of dietary fucoidan on growth, immune functions, blood characteristics
      and oxidative stress resistance of juvenile red sea bream, Pagrus major.
AB  - We determined the supplementation effects of dietary fucoidan on growth, immune
      responses, blood characteristics, and oxidative stress resistance of juvenile red
      sea bream. A fishmeal (FM)-based basal diet supplemented with 0% (D1, control),
      0.05% (D2), 0.1% (D3), 0.2% (D4), 0.4% (D5), and 0.8% (D6) mozuku fucoidan to
      formulate six experimental diets. Each diet was randomly allocated to triplicate
      groups of fish (3.8 g) for 60 days. Results showed that fish-fed diet D5 showed
      significantly higher (P < 0.05) growth performance compared to the control (D1).
      Diet groups D2 to D4 also showed intermediate values compared to D1. Feed
      conversion efficiency and protein efficiency ratio were significantly higher in
      diet group D5, which was not significantly different with D3. Fucoidan
      supplementation increased whole-body lipid, which was significantly higher in the
      D5 group. Condition factor (CF) was significantly higher in fish fed >= 0.2%
      fucoidan-supplemented diet groups. Diet group D5 and D4 showed significantly
      lower blood urea nitrogen (BUN) and aspartate aminotransferase (AST) level,
      respectively. Dietary fucoidan reduced the oxidative stress of fish. Among the
      measured nonspecific immune parameters, only peroxidase activity (PA) and total
      serum protein (TSP) were significantly influenced by dietary supplementation and
      it was higher in D4 group. Fucoidan supplementation reduces thiobarbituric acid
      reactive substance (TBARS) values numerically and it was lowest in fish-fed diet
      group D5. Under the present experimental condition, finally, we concluded that
      0.3-0.4% dietary fucoidan supplementation enhanced the growth and health
      performance of red sea bream by increasing growth, immune response, blood
      characteristics, and oxidative stress resistance.

PMID- 30291546
TI  - Stereotactic Body Radiation Therapy (SBRT) Using CyberKnife in Oligometastatic
      Cancer Patients; Retrospective Evaluation, Single Institution Experience.
AB  - OBJECTIVES: We retrospectively evaluate local control rate at 6 months and 1 year
      in oligometastatic cancer patients treated with SBRT using CyberKnife. METHODS:
      Total of 21 patients with 24 treatment sites from February 2014 till June 2017
      who were treated with SBRT in our institution were included in this study.
      RESULTS: Eleven patients were males, 10 patients were females, median age at
      diagnosis was 63 years, and colorectal cancer is the most commonly diagnosed
      cancer in 18 patients. The abdomino-pelvic lymph nodes were the commonest
      treatment site in 11 (45.8%), average PTV volume of 46.4 cc. All the patients
      received SBRT with average (BED) of 97 GY, 7 treatment sites received BED of <
      100GYgroup 1, and 17 received BED >= 100GY group 2. No reported G3 or G4 acute or
      chronic toxicity. The 6 months and 1 year local control (LC) were 95.8 and 88.2%,
      respectively. After a median follow-up of 16.8 months, 19(90.5%) patients were
      alive; among them, local progression was observed in 1 (4.1%) treatment site,
      while systemic progression in 4 (16.6%), and two (9.5%) patients died; they had
      both local and systemic failures. The 1-year local PFS rate was 82%. In
      univariate analysis, PTV volume was significantly correlated with LC rate at 6
      months (p = 0.001), while the site of metastasis appeared to significantly
      correlate with PFS (p = 0.03). CONCLUSION: SBRT using CyberKnife is feasible,
      safe, and effective treatment for oligometastatic sites. Six months and 1 year
      local control rate is 95.8 and 88.2% respectively in our patients cohort,
      treatment regimens with higher BED resulting in better 1-year local PFS, although
      it was not statistically significant. A larger cohort of patients and longer
      follow up is required for better evaluation.

PMID- 30291547
TI  - Animation as Supplementary Learning Material About Carcinogenic Liver Fluke in
      Classes for Primary Schoolchildren.
AB  - Carcinogenic liver fluke is still an issue of great concern in some countries of
      Southeast Asia, particularly in Thailand, Cambodia, the Lao People's Democratic
      Republic, and Vietnam. The infection, caused by Opisthorchis viverrini, is
      associated to cholangiocarcinoma and is endemic among human populations for whom
      raw fish is frequently consumed. Prevention and health education are required.
      Therefore, this study aimed to evaluate the effectiveness of educational
      intervention to improve knowledge among primary schoolchildren based on animation
      assisted education. In this study, 80 participants (40 participants in the
      experimental group and 40 participants in the comparison group) were selected in
      2018. The effectiveness of an interactive animation program in improving the
      knowledge of students studying liver fluke was determined based on scores on
      tests given before and immediately after completion of a 4.29-min animated
      program on the liver fluke life cycle, risk factors, disease, diagnosis,
      treatment, prevention, and control. Data were analyzed using SPSS-22 via paired t
      tests and independent samples t tests at a significance level of 0.05. A marked
      and significant improvement was observed in the immediate posttest compared with
      the pretest scores. More importantly, the students who had used the animated
      program achieved a significantly higher score on the final test than the
      comparison group. The results offered in the first report show that the use of
      the animated program facilitated education about liver fluke. It is strongly
      believed that animations are good supplementary learning materials for students,
      particularly for learning about serious concepts.

PMID- 30291548
TI  - Sensor applications of polypyrrole for oxynitrogen analytes: a DFT study.
AB  - Density functional theory calculations are performed to evaluate the sensing
      ability of polypyrrole for oxynitrogen analytes. Interaction energies of PPy-X (X
      = NO2-, NO2, and NO) are calculated at B3LYP-CP/6-31G(d) and B3LYP/6-31G(d)
      levels of theory and compared with the high level calibrated method (M05-2X/aug
      cc-pVDZ). B3LYP-CP/6-31G(d) gives the best correlation with the high level
      calibrated method compared to B3LYP/6-31G(d). Interaction of oligopyrrole with
      analytes shows a significant effect on the geometric and electronic properties;
      the conjugation is increased in the pyrrole oligomers and movement of charge is
      increased over the polymeric backbone. The charge is transferred from analytes to
      pyrrole oligomers (except nPy-NO2), and a more pronounced effect of charge
      transfer is observed in the case of nitrite ion (NO2-) compared to NO. In nPy
      NO2, the charge is transferred from polymer to analyte. This transfer of charge
      indicates the n-type doping effect of analytes. The HOMO-LUMO gap decreases after
      interaction with analytes, which results in a drop of resistance (conductivity
      increases). These theoretical outcomes are consistent with the experimental
      results; polypyrrole has more sensing ability toward the nitrite anion (NO2-).
      Graphical abstract High sensitivity of polypyrrole towards NO over NO2 and NO2.

PMID- 30291550
TI  - A Short Review of the Treatment of Headaches Using Osteopathic Manipulative
      Treatment.
AB  - PURPOSE OF REVIEW: This review highlights the importance of osteopathic
      manipulative treatment (OMT) in headache sufferers. OMT is a viable option for
      patients who either do not wish to use pharmaceuticals or who have
      contraindications to pharmaceuticals. Patients with headaches that are refractory
      to other treatment options may also be candidates for OMT. Multiple headache
      etiologies are amenable to this non-invasive treatment option and they will be
      reviewed here. Although there are advantages to using this treatment method,
      there are also shortcomings in the literature, which will be discussed. RECENT
      FINDINGS: Roughly 45 million Americans suffer from headaches every year. Many
      headache sufferers are unable to find relief through conventional treatment
      options. OMT is a useful non-invasive treatment option with little to no side
      effects. There are multiple headache types. Migraine, tension-type headache,
      combat-related events, post-traumatic headache, sinusitis, tooth extraction,
      concussions, and others have all shown benefit from OMT. OMT is a non-invasive
      treatment option for individuals suffering from various types of headaches. This
      treatment option is tailored to the individual needs of the patient and is
      delivered by licensed and experienced osteopathic physicians. This review of
      literature also highlights where there is need for further research in the field.

PMID- 30291549
TI  - A Critical Exploration of Migraine as a Health Disparity: the Imperative of an
      Equity-Oriented, Intersectional Approach.
AB  - PURPOSE OF REVIEW: Despite recognition of rising prevalence and significant
      burden, migraine remains underestimated, underdiagnosed, and undertreated. This
      is especially true among groups who have been historically, socially, and
      economically marginalized such as communities of color, women, people
      experiencing poverty, people with lower levels of education, and people who hold
      more than one of these marginalized identities. While there is growing public and
      professional interest in disparities in migraine prevalence, there is a paucity
      of research focusing on racial/ethnic and socioeconomic disparities, and the
      social and structural determinants of health and equity that perpetuate these
      disparities. From a health equity perspective, migraine research and treatment
      require an examination not only of biological and behavioral factors, but of
      these identities and underlying, intersecting social and structural determinants
      of health. RECENT FINDINGS: Significant disparities in migraine incidence,
      prevalence, migraine-related pain and disability, access to care, and quality of
      care persist among marginalized and underserved groups: African Americans,
      Hispanics, people experiencing poverty, un- or under-employment, the un- and
      under-insured, people who have been exposed to stressful and traumatic events
      across the lifespan, and people experiencing multiple, overlapping marginalized
      identities. These same groups are largely underrepresented in migraine research,
      despite bearing disproportionate burden. Current approaches to understanding
      health disparities in migraine largely assume an essentializing approach, i.e.,
      documenting differences between single identity groups-e.g., race or income or
      education level-rather than considering the mechanisms of disparities: the social
      and structural determinants of health. While disparities in migraine are becoming
      more widely acknowledged, we assert that migraine is more aptly understood as a
      health equity issue, that is, a condition in which many of the health disparities
      are avoidable. It is important in research and clinical practice to consider
      perspectives that incorporate a cultural understanding of racial, ethnic, and
      socioeconomic identity within and across all levels of society. Incorporating
      perspectives of intersectionality provides a strong foundation for understanding
      the role of these complex combination of factors on migraine pain and treatment.
      We urge the adoption of intersectional and systems perspectives in research,
      clinical practice, and policy to examine (1) interplay of race, gender, and
      social location as key factors in understanding, diagnosing, and treating
      migraine, and (2) the complex configurations of social and structural
      determinants of health that interact to produce health inequities in migraine
      care. An intentional research and clinical focus on these factors stands to
      improve how migraine is identified, documented, and treated among marginalized
      populations.

PMID- 30291551
TI  - Sustained conscious access to incidental memories in RSVP.
AB  - In visual search of natural scenes, differentiation of briefly fixated but task
      irrelevant distractor items from incidental memory is often comparable to
      explicit memorization. However, many characteristics of incidental memory remain
      unclear, including the capacity for its conscious retrieval. Here, we examined
      incidental memory for faces in either upright or inverted orientation using Rapid
      Serial Visual Presentation (RSVP). Subjects were instructed to detect a target
      face in a sequence of 8-15 faces cropped from natural scene photographs
      (Experiment 1). If the target face was identified within a brief time window, the
      subject proceeded to an incidental memory task. Here, subjects used incidental
      memory to discriminate between a probe face (a distractor in the RSVP stream) and
      a novel, foil face. In Experiment 2 we reduced scene-related semantic coherency
      by intermixing faces from multiple scenes and contrasted incidental memory with
      explicit memory, a condition where subjects actively memorized each face from the
      sequence without searching for a target. In both experiments, we measured
      objective performance (Type 1 AUC) and metacognitive accuracy (Type 2 AUC),
      revealing sustained and consciously accessible incidental memory for upright and
      inverted faces. In novel analyses of face categories, we examined whether
      accuracy or metacognitive judgments are affected by shared semantic features
      (i.e., similarity in gender, race, age). Similarity enhanced the accuracy of
      incidental memory discriminations but did not influence metacognition. We
      conclude that incidental memory is sustained and consciously accessible, is not
      reliant on scene contexts, and is not enhanced by explicit memorization.

PMID- 30291552
TI  - Helmets improve estimations of depth and visual angle to safe targets.
AB  - Egocentric distance estimation has been shown to depend on wearing safety gear,
      which promotes compensatory behavior, and on target type, which regulates fight
      or-flight responses. We hypothesized that the two factors interact, possibly in
      asymmetric fashion, and set out to uncover the limits of this interaction in a
      perceptual task where individuals wearing helmets or baseball caps estimated
      egocentric distance to non-threatening and threatening animals depicted on cards
      (i.e., safe and unsafe targets). We found that, compared to participants wearing
      caps, participants wearing helmets overshoot distance estimations and were able
      to distinguish not only between targets situated at two depth levels as
      participants wearing caps could, but also between safe targets situated at wide
      and narrow visual angles. Our findings help define the interaction between safety
      devices and target type, thereby contributing to the debate between advocates of
      prevention models and those who maintain that these are offset by compensatory
      strategies.

PMID- 30291553
TI  - The emotional attentional blink is robust to divided attention.
AB  - The emotional attentional blink (EAB) refers to a temporary impairment in the
      ability to identify a target when it is preceded by an emotional distractor. It
      is thought to occur because the emotional salience of the distractor exogenously
      captures attention for a brief duration, rendering the target unattended and
      preventing it from reaching awareness. Here we tested the extent to which the EAB
      can be attenuated by inducing a diffuse top-down attentional state, which has
      been shown to improve target identification in an analogous attentional
      phenomenon, the attentional blink. Rapid sequences of landscape images were
      presented centrally, and participants reported the orientation of a +/- 90
      degrees  rotation of a landscape target. To induce a diffuse state of attention,
      participants were given a secondary task of monitoring for the appearance of a
      colored dot in the periphery. We found that emotional distractors impaired target
      recognition performance to comparable extents, regardless of whether or not
      participants concurrently performed the peripheral-monitoring task. Moreover, we
      found that performance of the secondary task led to an impaired ability to ignore
      neutral distractors. Subjective ratings of target vividness mirrored the
      behavioral accuracy, with frequent reports of intermediate levels of vividness
      suggesting that the EAB might impair target visibility in a graded manner. Our
      results demonstrate that the EAB is robust to manipulations of top-down
      attention, suggesting that the temporary capture of attention by emotionally
      salient stimuli involves processes that are distinct from those that produce the
      attentional blink.

PMID- 30291555
TI  - Validation d'un questionnaire auto-administre sur les valeurs en politique
      publique de sante.
AB  - OBJECTIVES: The aims of this article are to describe the development of a self
      administered questionnaire assessing the core values in the field of public
      health ( radardesvaleurs.com ) and to report the results of a study testing the
      questionnaire's test-retest reliability, internal consistency and construct
      validity. METHOD: A 24-item questionnaire grounded in the conceptual framework of
      Shalom H. Schwartz (2000) was developed by a group of international experts in
      public health. Six scores were generated, each linked to a specific value and put
      on three axes: individualism-equity, autonomy-conformity and risk-security. The
      questionnaire was submitted to students attending the School of Public Health of
      the Universite de Montreal (ESPUM) (n = 700). A total of 401 students completed
      the questionnaire, 52 of whom completed it again one month later. RESULTS: For
      the test-retest reliability, all percentages of agreement were equal or superior
      to 60% except for a single question (50%). All Cohen's kappa coefficients of
      individual items were strong (> 0.60) except for three questions which presented
      a very high percentage of agreement. The Intraclass Correlation coefficients of
      the values' scores varied between 0.27 and 0.77. The three axes' internal
      consistency was estimated by Cronbach's alphas (between 0.46 and 0.74). The
      exploratory factorial analysis only partially confirmed the questionnaire's
      theoretical structure. CONCLUSION: Despite the limits of the results, the
      questionnaire has an interesting level of reliability and validity, which makes
      its pedagogical use pertinent to pursue. The limitation to four items/value, as
      well as the representativeness of the sampling (ESPUM students), could explain
      certain empirical shortcomings of the questionnaire.

PMID- 30291554
TI  - Episodic Migraine With and Without Aura: Key Differences and Implications for
      Pathophysiology, Management, and Assessing Risks.
AB  - PURPOSE OF REVIEW: To review the pathophysiologic, epidemiologic, and clinical
      evidence for similarities and differences between migraine with and without aura.
      RECENT FINDINGS: The ICHD-3 has recently refined the diagnostic criteria for aura
      to include positive symptomatology, which better differentiates aura from TIA.
      Although substantial evidence supports cortical spreading depression as the cause
      of visual aura, the role (if any) of CSD in headache pain is not well understood.
      Recent imaging evidence suggests a possible hypothalamic origin for a headache
      attack, but further research is needed. Migraine with aura is associated with a
      modest increase in the risk of ischemic stroke. The etiology for this association
      remains unclear. There is a paucity of evidence regarding treatments specifically
      aimed at the migraine with aura subtype, or whether migraine with vs without aura
      responds to treatment differently. Migraine with typical aura is therefore often
      treated similarly to migraine without aura. Lamotrigine, daily aspirin, and
      flunarizine have evidence for efficacy in prevention of migraine with aura, and
      magnesium, ketamine, furosemide, and single-pulse transcranial magnetic
      stimulation have evidence for use as acute treatments. Although triptans have
      traditionally been contraindicated in hemiplegic migraine and migraine with
      brainstem aura, this prohibition is being reconsidered in the face of evidence
      suggesting that use may be safe. The debate as to whether migraine with and
      without aura are different entities is ongoing. In an era of sophisticated
      imaging, genetic advancement, and ongoing clinical trials, efforts to answer this
      question are likely to yield important and clinically meaningful results.

PMID- 30291556
TI  - Initial Benchmarking of the Liquid Sampling-Atmospheric Pressure Glow Discharge
      Orbitrap System Against Traditional Atomic Mass Spectrometry Techniques for
      Nuclear Applications.
AB  - The integration of the liquid sampling-atmospheric pressure glow discharge (LS
      APGD) ion source with Orbitrap mass spectrometers has resulted in new
      opportunities in the field of isotope ratio mass spectrometry. In a field that
      has been dominated by thermal ionization mass spectrometry (TIMS) and inductively
      coupled plasma mass spectrometry (ICP-MS) on quadrupole and scanning-mode sector
      field analyzer platforms for highly accurate and precise measurements, the LS
      APGD-Orbitrap system offers a benchtop instrument capable of meeting the rigorous
      International Target Values for measurement uncertainty for uranium (U). In order
      to benchmark the LS-APGD-Orbitrap, a series of U certified reference materials
      with increasing 235U isotopic composition were analyzed. By using U samples
      ranging in enrichment from 1 to 80%, the ability of the system to measure isotope
      ratios over a wide range is demonstrated. This analysis represents the first time
      that the LS-APGD-Orbitrap system has been used to analyze highly enriched U
      samples, allowing for the measurement of each of the U isotopes, including 234U
      and 236U-related species, which had not been achieved previously. Ultimately, the
      LS-APGD-Orbitrap system was able to measure CRM U-800 (assayed as 235U / 238U =
      4.265622) as 4.266922, with a combined uncertainty, (uc), of 0.040%. These
      results are compared to those obtained using traditional elemental mass
      spectrometers including TIMS and ICP-MS-based instruments. The effectiveness of
      the LS-APGD-Orbitrap MS system for measuring U isotopes shows excellent promise
      in nuclear forensics, safeguards, and other nuclear weapon-based applications.
      Graphical Abstract ?.

PMID- 30291557
TI  - Cytomegalovirus meningitis in a patient with relapsed acute myeloid leukemia.
AB  - Cytomegalovirus meningitis/meningoencephalitis is a potentially fatal
      complication following hematopoietic stem cell transplantation that causes
      significant morbidity and mortality. In the pre-transplant setting, a few cases
      involving lymphoid malignancies have been reported. However, there have been no
      reports of patients with myeloid malignancies. A 36-year-old man with relapsed
      acute myeloid leukemia received high-dose cytarabine-containing salvage
      chemotherapies and then developed grade 4 lymphopenia for more than one month.
      Subsequently, the patient developed pyrexia, accompanying headache, nausea, and
      vomiting with no abnormal brain imaging. Despite receiving antimicrobial
      treatment, his febrile status and headache persisted. Given that the patient had
      symptoms consistent with viral meningitis with no evidence of etiology other than
      positive cytomegalovirus-DNA in his cerebrospinal fluid and cytomegalovirus pp65
      antigenemia, cytomegalovirus meningitis was diagnosed. After commencing
      ganciclovir treatment, the patient's headache and febrile status rapidly
      improved. Cytomegalovirus meningitis/meningoencephalitis is rare before
      hematopoietic stem cell transplantation, but may be useful in differential
      diagnoses in heavily treated acute myeloid leukemia patients with central nervous
      system symptoms.

PMID- 30291558
TI  - Venous thromboembolism in relapsed or refractory multiple myeloma patients
      treated with lenalidomide plus dexamethasone.
AB  - Lenalidomide plus dexamethasone (LD) is currently the mainstay of treatment for
      both untreated and relapsed or refractory multiple myeloma (RRMM). Although
      lenalidomide-associated venous thromboembolism (VTE) is a major clinical concern,
      its incidence and prognostic impact have not been delineated. In this nationwide
      retrospective cohort study, we aimed to determine the cumulative incidence of VTE
      and its prognostic value using two consecutive cohorts of LD-treated RRMM
      patients: the KMM151 cohort (N = 542) and the HIRA cohort (N = 1559). Data were
      collected from medical records for the KMM151 cohort and healthcare insurance
      claims database for the HIRA cohort. Throughout the study period, 24 patients
      (4.4%) in the KMM151 cohort and 80 patients (5.1%) in the HIRA cohort developed
      VTE. The cumulative incidence reached a plateau approximately 2 years after LD
      initiation. The 2-year incidence was 4.9% in the KMM151 cohort and 8% in the HIRA
      cohort. Higher starting dose of lenalidomide, previous history of VTE, and older
      age were associated significantly with an increased VTE risk. Early-onset VTE was
      associated significantly with poor survival. In conclusion, VTE occurred in 5-8%
      of RRMM patients treated with LD over 2 years, and early-onset VTE was a strong
      indicator of poor prognosis.

PMID- 30291559
TI  - Implementation of day of surgery admission for rectal cancer surgery in Ireland
      following a national centralisation programme.
AB  - BACKGROUND: Centralisation of rectal cancer surgery has altered the delivery of
      colorectal cancer care in Ireland. This has resulted in an increased demand for
      elective surgical beds in designated centres. AIM: This study aimed to assess if
      day of surgery admission (DOSA), in conjunction with implementation of a
      coordinated enhanced recovery pathway can reduce length of stay following
      elective rectal cancer resection. METHODS: This is a retrospective review from a
      single institution. Our prospectively maintained Dendrite(r) Database was
      interrogated. Three time points were analysed across a 7-year period (2011, 2012,
      2016). The first predates the introduction of a dedicated DOSA programme, the
      next was directly thereafter, and the final was 5-years post-implementation.
      These dates coincide with the centralisation of rectal cancer surgery to this
      centre. Outcomes included unadjusted length of stay and rates of DOSA pre-and
      post-implementation of the programme. RESULTS: The introduction of a DOSA pathway
      resulted in a fivefold increase in day of surgery admissions and a related 3-day
      reduction in average length of stay within a single year of implementation. This
      further improved in 2016, showing an almost 83% increase (15.90-98.50%) in day of
      surgery admission and a reduction in average length of stay from 16.4 to 12.4
      days when compared to 2011. CONCLUSIONS: Despite an increase in caseload of 54%,
      an estimated 272 bed days were saved. This demonstrated that DOSA is sustainable
      and highly effective in tackling the increased inpatient bed demands associated
      with the growing requirement for elective surgery.

PMID- 30291560
TI  - Inflammation as a Regulator of the Renin-Angiotensin System and Blood Pressure.
AB  - PURPOSE OF REVIEW: Mechanisms facilitating progression of hypertension via cross
      stimulation of the renin-angiotensin system (RAS) and inflammation have been
      proposed. Accordingly, we review and update evidence for regulation of RAS
      components by pro-inflammatory factors. RECENT FINDINGS: Angiotensin II (Ang II),
      which is produced by RAS, induces vasoconstriction and consequent blood pressure
      elevation. In addition to this direct action, chronically elevated Ang II
      stimulates several pathophysiological mechanisms including generation of
      oxidative stress, stimulation of the nervous system, alterations in renal
      hemodynamics, and activation of the immune system. In particular, an activated
      immune system has been shown to contribute to the development of hypertension.
      Recent studies have demonstrated that immune cell-derived pro-inflammatory
      cytokines regulate RAS components, further accelerating systemic and local Ang II
      formation. Specifically, regulation of angiotensinogen (AGT) production by pro
      inflammatory cytokines in the liver and kidney is proposed as a key mechanism
      underlying the progression of Ang II-dependent hypertension.

PMID- 30291561
TI  - Quality of diabetes care in breast, colorectal, and prostate cancer.
AB  - PURPOSE: Overlooking other medical conditions during cancer treatment and follow
      up could result in excess morbidity and mortality, thereby undermining gains
      associated with early detection and improved treatment of cancer. We compared the
      quality of care for diabetes patients subsequently diagnosed with breast,
      colorectal, or prostate cancer to matched, diabetic non-cancer controls. METHODS:
      Longitudinal cohort study using primary care records from the Clinical Practice
      Research Datalink, United Kingdom. Patients with pre-existing diabetes were
      followed for up to 5 years after cancer diagnosis, or after an assigned index
      date (non-cancer controls). Quality of diabetes care was estimated based on
      Quality and Outcomes Framework indicators. Mixed effects logistic regression
      analyses were used to compare the unadjusted and adjusted odds of meeting quality
      measures between cancer patients and controls, overall and stratified by type of
      cancer. RESULTS: 3382 cancer patients and 11,135 controls contributed 44,507
      person-years of follow-up. In adjusted analyses, cancer patients were less likely
      to meet five of 14 quality measures, including: total cholesterol <= 5 mmol/L
      (odds ratio [OR] = 0.82; 95% confidence interval [CI], 0.75-0.90); glycosylated
      hemoglobin <= 59 mmol/mol (adjusted OR = 0.77; 95% CI, 0.70-0.85); and albumin
      creatinine ratio testing (adjusted OR = 0.83; 95% CI, 0.75-0.91). However, cancer
      patients were as likely as their matched controls to meet quality measures for
      other diabetes services, including retinal screening, foot examination, and
      dietary review. CONCLUSIONS: Although in the short-term, cancer patients were
      less likely to achieve target thresholds for cholesterol and HbA1c, they
      continued to receive high-quality diabetes primary care throughout 5 years post
      diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: These findings are important for
      cancer survivors with pre-existing diabetes because they indicate that high
      quality diabetes care is maintained throughout the continuum of cancer diagnosis,
      treatment, and follow-up.

PMID- 30291563
TI  - Rapidly progressive encephalopathy caused by Coxsackie meningoencephalitis in an
      elderly male.
AB  - Enteroviruses and Coxsackie viruses are common causes of aseptic meningitis and
      encephalitis in children. These infections usually have a benign, self-limited
      course. However, they can have a florid presentation in immunocompromised
      patients, such as neonates, patients exposed to immunosuppressive drugs, such as
      transplant recipients and patients with agammaglobulinemia. We present a rare
      case of rapidly progressive acute encephalopathy caused by Coxsackie
      meningoencephalitis and complicated by refractory status epilepticus in an
      immunocompetent adult male. Our case highlights the importance of having a broad
      differential in patients presenting with rapidly progressive acute
      encephalopathy. Although rare, an enterovirus infection caused by a Coxsackie
      virus subtype can have a severe presentation causing significant morbidity. This
      case, also underscores the importance of searching for underlying
      immunodeficiency in malignant presentations of common viral infections. Hence,
      rapidly progressive acute encephalopathy due to coxsackievirus can occur in
      immunocompetent individuals. Aggressive and systematic diagnostic and therapeutic
      approach in such severe cases can influence overall outcomes.

PMID- 30291564
TI  - Genetic characterization of measles virus genotype D6 subacute sclerosing
      panencephalitis case, Alberta, Canada.
AB  - Subacute sclerosing panencephalitis (SSPE) is a progressive and eventually fatal
      neurological disease arising from a persistent infection with measles virus (MV)
      acquired at a young age. SSPE measles virus strains are defective and unable to
      produce progeny virions, due to multiple and extensive mutations in a number of
      key genes. We sequenced the full MV genome from our recently reported SSPE case,
      which typed as genotype D6, and compared it with other genotype D6 wild type and
      SSPE sequences. The Alberta D6 strain was significantly different from other
      reported SSPE D6 sequences. Mutations were observed in all the genes of the
      Alberta strain, with the greatest sequence divergence noted in the M gene with
      17.6% nucleotide and 31% amino acid variation. The L gene showed the least
      variation with 1.3% nucleotide and 0.7% amino acid differences respectively. The
      nucleotide variability for 15,672 bases of the complete genome compared to the
      wild type and other SSPE D6 strains was around 3%.

PMID- 30291562
TI  - Triggers, Protectors, and Predictors in Episodic Migraine.
AB  - PURPOSE OF REVIEW: A wide variety of triggers prompt attacks in episodic
      migraine. Although experimental triggers such as glyceryl trinitrate reliably
      produce migraine, natural triggers are much less predictable and vary in
      importance between individuals. This review describes the most common triggers in
      episodic migraine and provides strategies for managing them in clinical practice.
      RECENT FINDINGS: Multiple migraine attack triggers have been established based on
      patient surveys, diary studies, and clinical trials. Stress, menstrual cycle
      changes, weather changes, sleep disturbances, alcohol, and other foods are among
      the most common factors mentioned. Clinical studies have verified that fasting,
      premenstrual periods in women, "letdown" after stress, and most likely low
      barometric pressures are migraine triggers. Premonitory symptoms such as neck
      pain, fatigue, and sensitivity to lights, sounds, or odors may mimic triggers.
      Multiple studies clearly demonstrate triggers in episodic migraine, often related
      to change in homeostasis or environment. Many common migraine triggers are not
      easily modifiable, and avoiding triggers may not be realistic. Healthy lifestyle
      choices such as exercise, adequate sleep, stress management, and eating regularly
      may prevent triggers and transformation to chronic migraine over time.

PMID- 30291565
TI  - Mechanisms of neuropathogenesis in HIV and HCV: similarities, differences, and
      unknowns.
AB  - HIV and hepatitis C virus (HCV) have both been associated with cognitive
      impairment. Combination antiretroviral therapy (cART) has dramatically changed
      the nature of cognitive impairment in HIV-infected persons, while the role of
      direct-acting antivirals (DAA) in neurocognition of HCV-infected individuals
      remains unclear. Also, whether HIV and HCV interact to promote neurocognitive
      decline or whether they each contribute an individual effect continues to be an
      open question. In this work, we review the virally mediated mechanisms of HIV-
      and HCV-mediated neuropathogenesis, with an emphasis on the role of dual
      infection, and discuss observed changes with HIV viral suppression and HCV
      functional cure on neurocognitive impairments.

PMID- 30291566
TI  - Incomplete myelopathy and human T cell lymphotropic virus type-1 (HTLV-1).
AB  - This was a cross-sectional prospective study. We performed a multivariate
      statistical analysis of the neurological signs and symptoms of patients infected
      with human T cell lymphotropic virus type 1 (HTLV-1) in an attempt to separate
      them into distinct groups and identify clinical-neurological manifestations that
      could differentiate the various profiles. The study was performed in the city of
      Belem (state of Para), located in the Amazon region of Brazil, from 2014 to 2016.
      We determined muscle strength and tone, reflexes, sensations, sphincter function,
      gait, and the Expanded Disability Status Scale score among individuals with HTLV
      I. We then used exploratory statistical methods in an attempt to find different
      profiles and establish distinct groups. We analyzed 60 patients with HTLV-1. The
      filtering of the data, performed with mixed PCA, gave rise to a streamlined
      database with the most informative data and suggested the formation of three
      statistically distinct groups: asymptomatic carriers (AC), mono/oligosymptomatic
      (MOS), and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSPd),
      AC and MOS (p = 0.002), AC and HAM/TSPd (p < 0.001), and HAM/TSPd and MOS (p =
      0.001). The subsequent cluster analysis confirmed the formation of three
      clusters. The classification and regression tree demonstrated that altered gait
      was the most important variable for the classification of an individual with
      HAM/TSPd and that, in the absence of this impairment, hyperreflexia characterized
      MOS. The present study was able to separate patients infected by HTLV-1 into
      three clinical groups (AC, HAM/TSPd, and MOS) and identify clinical
      manifestations that could differentiate the various patient groups.

PMID- 30291568
TI  - Comparison of oral flora before and after triple therapy for Helicobacter pylori
      eradication in patient with gastric disease.
AB  - The oral cavity is recognized as a major route for infection by Helicobacter
      pylori, which colonizes the gastric mucosa. Therapeutic options for elimination
      in patients with digestive disease have been established, though whether
      antibiotics are effective for H. pylori harbored in the oral cavity as well as
      oral commensal bacteria remain unknown. A 29-year-old woman visited a
      gastrointestinal clinic with a chief complaint of stomach ache. Gastroscopy and
      urine test findings for H. pylori IgG led to a definitive diagnosis of goose
      bumps gastritis induced by bacteria in the stomach, and triple therapy for H.
      pylori eradication was administered. Oral samples were obtained 10 times at a
      dental hospital clinic from 1 week before until 6 months after starting triple
      therapy. Nested PCR amplifying the ureA gene and PCR assays using species
      specific primer sets were performed to detect H. pylori and major oral commensal
      bacterial species, respectively, in those samples. Bacterial DNA encoding the
      ureA gene of H. pylori in oral specimens was detected prior to starting therapy,
      which was then reduced during and not detected after finishing treatment.
      Although the populations of major oral pathogenic bacteria, such as
      periodontopathic and oral streptococcal species, were drastically reduced during
      triple therapy, most had recovered within approximately 1 week after ending
      treatment. These results suggest that a conventional triple therapy approach for
      eradication of H. pylori in cases of digestive disease is effective for
      elimination of the bacterium from the oral cavity. On the other hand, after
      finishing such therapy, the oral flora composition is not drastically changed.

PMID- 30291567
TI  - White matter damage, neuroinflammation, and neuronal integrity in HAND.
AB  - HIV-associated neurocognitive disorders (HANDs) persist even with virologic
      suppression on combination antiretroviral therapy (cART), and the underlying
      pathophysiological mechanisms are not well understood. We performed structural
      magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without
      major neurocognitive comorbidities. Study participants were classified as
      neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive
      disorder (MND), or HIV-associated dementia (HAD). Using structural MRI, we
      measured volumes of cortical and subcortical gray matter and total and abnormal
      white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal
      gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions.
      Adjusted odds ratios were used to compare HAND to NU. Among 253 participants, 40%
      met HAND criteria (21% ANI, 15% MND, and 4% HAD). Higher risk of HAND was
      associated with more aWM. Both HAD and MND also had smaller gray and white matter
      volumes than NU. Among individuals with undetectable plasma HIV RNA, structural
      volumetric findings were similar to the overall sample. MND had lower FWM
      creatine and higher FGM choline relative to NU, whereas HAD and ANI had lower BG
      N-acetyl aspartate relative to NU. In the virologically suppressed subgroup,
      however, ANI and MND had higher FGM choline compared to NU. Overall, HAND showed
      specific alterations (more aWM and inflammation; less gray matter volume and
      lower NAA). Some MR measures differentiated less severe subtypes of HAND from
      HAD. These MR alterations may represent legacy effects or accumulating changes,
      possibly related to medical comorbidities, antiretroviral therapy, or chronic
      effects of HIV brain infection.

PMID- 30291569
TI  - Rhesus Macaque Brain Atlas Regions Aligned to an MRI Template.
AB  - To aid in the analysis of rhesus macaque brain images, we aligned digitized
      anatomical regions from the widely used atlas of Paxinos et al. to a published
      magnetic resonance imaging (MRI) template based on a large number of subjects.
      Digitally labelled atlas images were aligned to the template in 2D and then in
      3D. The resulting grey matter regions appear qualitatively to be well registered
      to the template. To quantitatively validate the procedure, MR brain images of 20
      rhesus macaques were aligned to the template along with regions drawn by hand in
      striatal and cortical areas in each subject's MRI. There was good geometric
      overlap between the hand drawn regions and the template regions. Positron
      emission tomography (PET) images of the same subjects showing uptake of a
      dopamine D2 receptor ligand were aligned to the template space, and good
      agreement was found between tracer binding measures calculated using the hand
      drawn and template regions. In conclusion, an anatomically defined set of rhesus
      macaque brain regions has been aligned to an MRI template and has been validated
      for analysis of PET imaging in a subset of striatal and cortical areas. The
      entire set of over 200 regions is publicly available at https://www.nitrc.org/ .
      Graphical Abstract ?.

PMID- 30291570
TI  - Estimation of annual effective dose due to ingestion of radioactive elements in
      Sri Lankan common meal plans.
AB  - Dietary ingestion of radionuclides by human may lead to many hazardous effects
      such as cancers. No studies have been conducted to estimate the levels of
      radioactivity dosage received from Sri Lankan homemade foods. In order to find
      out the levels of radionuclides in Sri Lankan cooked foods, meal plans (n = 11)
      that are most commonly consumed were analyzed for the activity concentrations of
      the radioisotopes 226Ra, 210Pb, 232Th, 137Cs, and 40K by means of gamma
      spectroscopy. 40K had the highest activity concentration present in the meal
      plans with a range of 80.56 +/- 17.53 to 143.41 +/- 24.6 Bq kg-1, and the
      radionuclides 226Ra, 210Pb, 137Cs, and 232Th were not detected in any of the
      analyzed meal plans. The annual intake of food was determined on the basis of
      their average annual consumption. The effective dose to an average adult who
      consumes the meal plans ranged from 0.030 to 0.051 mSv year-1. However, the
      effective dose and activity concentrations of radionuclides were lower than the
      guideline limit specified by United Nations Scientific Committee on the Effects
      of Atomic Radiation-1 and other countries. Hence, the consumption of cooked meal
      plans in Sri Lanka is safe in terms of radioactivity for the five radionuclides
      investigated in this study.

PMID- 30291571
TI  - Buprenorphine for Chronic Pain: a Systemic Review.
AB  - PURPOSE OF REVIEW: The purpose of this review is to evaluate and explain our
      current understanding of the clinical use of buprenorphine in the treatment of
      chronic pain. RECENT FINDINGS: There has been few high-quality, unbiased studies
      performed on the use of buprenorphine in the treatment of chronic pain.
      Buprenorphine is an effective and safe analgesic that is tolerated at least as
      well, if not better, than other opioids. Given its safety and mechanistic
      advantages, the authors believe there is an important role for buprenorphine in
      the treatment of chronic pain severe enough to warrant the use of an opioid
      analgesic. Though data is lacking for superiority in chronic pain states, the
      other advantages of the molecule make it the preferential first-line opioid for
      around-the-clock pain in our practice.

PMID- 30291572
TI  - What Are We Missing in the Diagnostic Criteria for Migraine?
AB  - PURPOSE OF REVIEW: This review is intended to examine how the diagnostic criteria
      for migraine have evolved over the past 45 years and to evaluate the strengths
      and weaknesses of the current diagnostic criteria promulgated by the
      International Classification of Headache Disorders (ICHD). RECENT FINDINGS: The
      ICHD is a comprehensive and systematic classification system for headache
      disorders. As the pathophysiology of migraine is more fully elucidated and more
      sophisticated diagnostic technologies are developed (e.g., the identification of
      biomarkers), the current diagnostic criteria for migraine will likely be further
      refined. The ICHD has allowed for more precise research study design in the field
      of headache medicine. The current diagnostic criteria for migraine outlined in
      the 3rd version of the ICHD are far more sensitive and specific than the clinical
      criteria proposed in 1962. In future iterations, dividing episodic and chronic
      migraine into subtypes based on frequency (i.e., low frequency vs high frequency;
      near-daily vs daily) potentially could assist in guiding clinical management. In
      addition, a better understanding of aura, vestibular migraine, migrainous
      infarction, and hemiplegic migraine likely will lead to more refined diagnostic
      criteria for those entities.

PMID- 30291573
TI  - Corticosteroid Receptors in the Brain: Transcriptional Mechanisms for Specificity
      and Context-Dependent Effects.
AB  - Corticosteroid hormones act in the brain to support adaptation to stress via
      binding to mineralocorticoid and glucocorticoid receptors (MR and GR). These
      receptors act in large measure as transcription factors. Corticosteroid effects
      can be highly divergent, depending on the receptor type, but also on brain
      region, cell type, and physiological context. These differences ultimately depend
      on differential interactions of MR and GR with other proteins, which determine
      ligand binding, nuclear translocation, and transcriptional activities. In this
      review, we discuss established and potential mechanisms that confer receptor and
      cell type-specific effects of the MR and GR-mediated transcriptional effects in
      the brain.

PMID- 30291574
TI  - Virtual touch IQ elastography in evaluation of Achilles tendon in patients with
      chronic renal failure.
AB  - PURPOSE: To evaluate the sonoelastographic changes in the Achilles tendon in
      patients with chronic renal failure (CRF) using virtual touch imaging
      quantification (VTIQ) elastography. METHODS: Twenty-six patients undergoing three
      hemodialysis sessions per week and 26 subjects admitted to our institution
      between January 2016 and April 2016 were included in this prospective study. The
      characteristics and body mass index of the patients were noted. Ultrasonography
      was performed parallel to the long axis of the bilateral Achilles tendons during
      relaxation of the legs using the Siemens Acuson S3000TM ultrasound device
      (Siemens HealthCare, Erlangen, Germany). Tendon thickness was reviewed, and
      tissue stiffness was quantitatively assessed using VTIQ elastography. Independent
      samples t test and Mann-Whitney U test were used for statistical analyses.
      RESULTS: The median values of shear wave velocities of the Achilles tendon in
      patients with CRF were 7.19 m/s (4.23-9.77 m/s) on the right and 6.98 m/s (4.00
      9.82 m/s) on the left, while they were 5.11 m/s (4.09-8.82 m/s) on the right and
      5.36 m/s (4.05-8.80 m/s) on the left in controls. The stiffness of the Achilles
      tendons in patients with CRF was found to be higher than that in controls (right:
      P < 0.001, left: P = 0.004). There was no statistically significant difference in
      tendon thickness between the CRF and control groups (P > 0.05). CONCLUSION: The
      thickness and stiffness of tendon can be effectively evaluated with
      sonoelastography. The thickness of the Achilles tendon did not significantly
      differ between the patients with CRF and healthy subjects. However, the stiffness
      of the Achilles tendon measured with VTIQ elastography was demonstrated to be
      increased in the patients with CRF.

PMID- 30291575
TI  - Three-dimensional sonographic minute structure analysis of fetal cerebellar
      vermis development and malformations: utilizing volume contrast imaging.
AB  - PURPOSE: To obtain three-dimensional ultrasonic (3D US) structural details and
      biometrics of the fetal cerebellar vermis and evaluate the value of developmental
      and malformation identification. METHODS: The 3D US minute structure of the fetal
      cerebellar vermis in mid-sagittal view was detected in normal fetuses (n = 438;
      16-41 weeks). Biometric sizes were measured to establish the stage-specific norms
      and reproducibility analysis. Additionally, 28 fetuses with suspected abnormal
      posterior fossa contents were assessed to analyze the clinical value. RESULTS:
      The minute structure of normal fetuses, including cerebellar vermis contours and
      the fastigial recess of the fourth ventricle, were visible around Week 19. The
      main lobules and fissures were apparent around Week 22, and all nine lobules,
      fissures, and the fourth ventricle were clearly displayed by Week 28. Cerebellar
      vermis biometric sizes (anterior-posterior length, cranio-caudal length,
      circumference, and surface area (SA)) grew in a linear fashion with high
      reliability, especially SA measurements (for intraclass, ICC 0.989, 95% CI (0.980
      0.994); for interclass, ICC 0.992, 95% CI (0.984-0.996)). On the middle sagittal
      section of 3D US, the SA reduced at least 50% in the Dandy-Walker group with no
      recognizable cerebellar vermis structures showing. The SA in vermian hypoplasia
      malformation reduced during [Formula: see text] to 50% with the primary/secondary
      fissures absent or partly absent and arborization of the lobules reduced. That
      would be an important diagnosis and antidiastole clue. Combined with minute
      structural observation, sonographic diagnoses were accurate in 88% of cases.
      CONCLUSION: Minute structures obtained by 3D US were clinically useful in the
      evaluation of cerebellar vermis development and cerebellar vermis malformations.

PMID- 30291576
TI  - Contrasted evolutionary constraints on carbohydrate active enzymes (CAZymes) in
      selected Frankia strains.
AB  - Carbohydrate active enzymes (CAZymes) are capable of breaking complex
      polysaccharides into simpler form. In plant-host-associated microorganisms
      CAZymes are known to be involved in plant cell wall degradation. However, the
      biology and evolution of Frankia CAZymes are largely unknown. In the present
      study, we took a genomic approach to evaluate the presence and putative roles of
      CAZymes in Frankia. The CAZymes were found to be potentially highly expressed
      (PHX) proteins and contained more aromatic amino acids, which increased their
      biosynthetic energy cost. These energy rich amino acids were present in the
      active sites of CAZymes aiding in their carbohydrate binding capacity.
      Phylogenetic and evolutionary analyses showed that, in Frankia strains with the
      capacity to nodulate host plants, CAZymes were evolving slower than the other PHX
      genes, whereas similar genes from non-nodulating (or ineffectively nodulating)
      Frankia strains showed little variation in their evolutionary constraints
      compared to other PHX genes. Thus, the present study revealed the persistence of
      a strong purifying selection on CAZymes of Frankia indicating their crucial role.

PMID- 30291577
TI  - Medication-related problems during transfer from hospital to home care: baseline
      data from Switzerland.
AB  - Background The shift from inpatient to ambulatory care has resulted in an
      increase in home care patients. Little is known regarding medication safety
      associated with patient transfer from hospital to home care. Objective To
      evaluate medication-related problems in patients transferring from hospital to
      home care in Switzerland. Setting A non-for-profit home care organization in the
      city of Lucerne/Switzerland. Methods We conducted a prospective observational
      study, including patients aged >= 64 years and receiving >= 4 medications at
      hospital discharge. Two structured questionnaires assessing the transfer process
      were completed by home care nurses. Prescription quality was assessed using a
      PCNE Type 2b Medication Review. Main outcome measures The quality of the transfer
      process was measured comparing agreed-upon with reported parameters. Prescription
      quality was analyzed assessing the unambiguity of the prescription. Potentially
      inappropriate medications (Priscus(r) list), contraindications, duplications and
      interactions, and clinical pharmacist-identified potential medication-related
      problems were collected. Results Study patients (n = 100) received 8.6 +/- 3.5
      regularly administered medications. Only 5/100 patients had a complete set of
      written discharge information. At the time of the first visit, 13/100 patients
      had no written medication information available. Discharge medication
      prescriptions were clear to nurses in 62% of patients. In 20 patients, the
      required medications were unavailable, resulting in 19 medication errors.
      Assessment by a clinical pharmacist revealed only 33/100 patients had a clear
      discharge prescription. Of a total of 984 prescribed drugs, 16% were considered
      to be ambiguous, 22 (2.2%) were potentially inappropriate. 7/984 drugs were
      contraindicated, 8 were duplicates. Conclusion In addition to the known risk
      factors in patients transferring from hospital to home care (age, polymedication,
      multiple providers), 3 major problems impacted upon medication safety: fragmented
      communication, unreliable medication availability and a poor prescription
      quality. Clinical pharmacists are an important option to improve medication
      safety ass.

PMID- 30291578
TI  - Nutritional epidemiology and cancer: A Tale of Two Cities.
AB  - Recently, Ioannidis questioned whether nutritional epidemiology could be
      reconciled with good scientific principles, and suggested that the field needs
      radical reform. One of the reforms he advocated was more randomized trials;
      though what diet would be tested and how it would be measured were unspecified,
      how adherence would be monitored was unclear or unimportant, and the length of
      time vaguely stated as "lifelong". The other reform was reanalysis of shared
      data, which actually already exists in a large number of cohort consortia of
      individual pooled data. The 2018 report analysis of diet and cancer from the
      World Cancer Fund/American Institute of Cancer Research presents a sharply
      different picture of our knowledge of nutrition and cancer, which has evolved
      immensely in the past 3 decades. Based on current knowledge, factors related to
      energy balance, encompassed by body mass anthropometric measures might account
      for about 10-15% of the U.S. cancer burden. This 10-15% encompasses physical
      activity and obesogenic effects of diet. About 5% may be attributable to alcohol,
      and another 5% to specific dietary factors combined (e.g., red and processed
      meat, whole grains, fiber, calcium, fruits, and vegetables). Surrogates such as
      attained height and age at menarche are influenced by nutrition and are
      consistent risk factors for cancer, supporting the importance of early nutrition.
      Recent data suggest that early life dietary patterns, which may be modifiable,
      may be important. Though important questions remain, our understanding of
      nutrition and cancer over the life course is coherent and has been informed by
      nutritional epidemiology and other data.

PMID- 30291579
TI  - A Stepwise Approach in Learning Surgical Residents a Roux-en-Y Gastric Bypass.
AB  - INTRODUCTION: This study describes a stepwise training program to teach a
      laparoscopic Roux-en-Y gastric bypass (LRYGB). Results of a resident are compared
      to experienced bariatric surgeons (EBS). METHODS: The resident performed a
      varying amount of surgical steps and the duration of every step was measured
      using video analysis. In order to compare the resident's results to EBS, the
      average time per step was calculated for 30 procedures. RESULTS: The total
      procedure time of LRYGB was 61.15 (+/- 8.74) min for a novice resident. In
      comparison, the average of three EBS was 36.22 (+/- 9.06) min. Creation of the
      gastric pouch had an average of 12.82 (+/- 4.08) versus 6.93 (+/- 2.58) min.
      Duration of creating the stapled gastrojejunostomy was 7.43 (+/- 2.11) versus
      4.48 (+/- 2.02) min. Suturing of the gastrojejunostomy was 12.60 (+/- 3.31)
      compared to 6.31 (+/- 2.53) min. Creating the jejunojejunal anastomosis had a
      duration of 7.12 ( +/-2.31) versus 4.22 (+/- 1.60) min and suturing this
      anastomosis was 13.93 (+/- 3.81) compared to 8.51 (+/- 3.37) min. At the end of
      the traineeship, the observed progression approximated the skills level of the
      EBS. CONCLUSION: The stepwise LRYGB-training program, analysed in this study, can
      result in an efficient and safe way to approach the learning curve to the level
      of the EBS. Within this training program, the total time of the operation is kept
      low in order to prevent adverse events for the patient and loss of efficiency in
      the bariatric program. The results of this study could act as a guideline for the
      development of such training programs.

PMID- 30291580
TI  - Baseline Pro-inflammatory Diet Is Inversely Associated with Change in Weight and
      Body Fat 6 Months Following-up to Bariatric Surgery.
AB  - OBJECTIVE: To evaluate whether the baseline Dietary Inflammatory Index (DII(r))
      was associated with weight loss and body composition change after bariatric
      surgery. METHODOLOGY: This longitudinal study included 132 women with obesity
      (BMI >= 35 kg/m2, 43.0 +/- 9.7 years), followed up for 6 months after bariatric
      surgery. The DII(r) was calculated from dietary data collected using 24-h dietary
      recall interviews. Anthropometric variables, socio demographic variables, health
      related habits, history of disease, as well as gastrointestinal symptoms, both in
      the preoperative period (baseline) and 6 months after bariatric surgery were
      collected from the patients' medical records. RESULTS: Individuals with a more
      pro-inflammatory diet (DII > 0.35 median value) preoperatively experienced
      smaller weight loss (- 22.7% vs. - 25.3%, p = 0.02) and fat mass loss (- 31.9 vs.
      - 36.2%, p = 0.026), with no difference in lean mass (p = 0.14). In a linear
      regression model, the baseline DII score was negatively associated with
      percentage change in weight and fat mass and positively associated with weight
      and fat mass in the sixth month after surgery. In addition, a pro-inflammatory
      baseline DII score was correlated with a lower intake of fruit (r = - 0.26, p =
      0.006), vegetables (r = - 0.47, p = 0.001), and legumes (r = - 0.21, p = 0.003)
      in the postoperative period. CONCLUSION: In this longitudinal study, a pro
      inflammatory diet at baseline was associated with smaller reductions in weight
      and body fat and poorer dietary quality (reduced consumption of fruits,
      vegetables, and legumes) 6 months after bariatric surgery.

PMID- 30291581
TI  - Citrate analysis using capillary electrophoresis and complexation with Eu3+
      tetracycline.
AB  - A sensitive assay for citrate was developed. Citrate was incubated with 50 MUM
      Eu3+-tetracycline and the complex separated using capillary electrophoresis
      utilizing post-column laser-induced luminescence detection in a sheath flow
      cuvette. Signal was linear with citrate concentration from 10 MUM to 200 nM.
      Injection volumes were 320 pL. For the 200 nM sample, this corresponds to the
      injection of 64 amoles of citrate. Separation time was < 90 s with a total run
      time of 5 min. As an application the method was used to analyze citrate in
      agricultural and medicinal products. The method was also used to develop an assay
      for the enzyme citrate synthase.

PMID- 30291582
TI  - Ictal Source Locations and Cortico-Thalamic Connectivity in Childhood Absence
      Epilepsy: Associations with Treatment Response.
AB  - Childhood absence epilepsy (CAE), the most common pediatric epilepsy syndrome, is
      usually treated with valproic acid (VPA) and lamotrigine (LTG) in China. This
      study aimed to investigate the ictal source locations and functional connectivity
      (FC) networks between the cortices and thalamus that are related to treatment
      response. Magnetoencephalography (MEG) data from 25 patients with CAE were
      recorded at 300 Hz and analyzed in 1-30 Hz frequency bands. Neuromagnetic sources
      were volumetrically scanned with accumulated source imaging. The FC networks
      between the cortices and thalamus were evaluated at the source level through a
      connectivity analysis. Treatment outcome was assessed after 36-66 months
      following MEG recording. The children with CAE were divided into LTG responder,
      LTG non-responder, VPA responder and VPA non-responder groups. The ictal source
      locations and cortico-thalamic FC networks were compared to the treatment
      response. The ictal source locations in the post-dorsal medial frontal cortex
      (post-DMFC, including the medial primary motor cortex and the supplementary
      sensorimotor area) were observed in all LTG non-responders but in all LTG
      responders. At 1-7 Hz, patients with fronto-thalamo-parietal/occipital (F-T-P/O)
      networks were older than those with fronto-thalamic (F-T) networks or other
      cortico-thalamic networks (p = 0.000). The duration of seizures in patients with
      F-T-P/O networks at 1-7 Hz was longer than that in patients with F-T networks or
      other cortico-thalamic networks (p = 0.001). The ictal post-DMFC source
      localizations suggest that children with CAE might experience initial LTG
      monotherapy failure. Moreover, the cortico-thalamo-cortical network is associated
      with age. Finally, the cortico-thalamo-cortical network consists of anterior and
      posterior cortices and might contribute to the maintenance of discharges.

PMID- 30291583
TI  - Effects of Neutralizing Antibody Production on AAV-PHP.B-Mediated Transduction of
      the Mouse Central Nervous System.
AB  - Adeno-associated virus (AAV)-PHP.B, a capsid variant of AAV serotype 9, is highly
      permeable to the blood-brain barrier. A major obstacle to the systemic use of AAV
      PHP.B is the generation of neutralizing antibodies (NAbs); however, temporal
      profiles of NAb production after exposure to AAV-PHP.B, and the influence on
      later AAV-PHP.B administration, remains unknown. To address these, AAV-PHP.Bs
      expressing either GFP or mCherry by neuron-specific or astrocyte-specific
      promoters were intravenously administered to mice at various intervals, and brain
      expression was examined. Injection of two AAV-PHP.Bs, separated temporally,
      showed that as little as a 1-day interval between injections resulted in a
      significant decrease in expression of the second transgene, with a complete loss
      of expression after 7 days, paralleling an increase in serum NAb titers. Brain
      parenchymal injection was explored to circumvent the presence of NAbs. Mice
      systemically pre-treated with an AAV-PHP.B were injected intra-cerebrally with an
      AAV-PHP.B expressing GFP. After 2 weeks, marked GFP expression in the cerebellum
      was evident, showing that pre-existing NAbs did not affect the AAV-PHP.B directly
      injected into the brain. In contrast, reversing the injection order, i.e.,
      cerebellar injection followed by systemic injection, completely eliminated
      expression of the second transgene. We confirmed that intra-cerebellar injection
      produced NAbs in the serum, but not in the cerebrospinal fluid (CSF). Our results
      indicate that the preclusion of brain transduction by a second AAV-PHP.B
      administration begins from the first day following systemic injection and is
      established within 1 week. Serum NAbs can be avoided by directly injecting AAV
      PHP.Bs into brain tissue.

PMID- 30291584
TI  - Crybb2 Mutations Consistently Affect Schizophrenia Endophenotypes in Mice.
AB  - As part of the betagamma-superfamily, betaB2-crystallin (CRYBB2) is an ocular
      structural protein in the lens, and mutation of the corresponding gene can cause
      cataracts. CRYBB2 also is expressed in non-lens tissue such as the adult mouse
      brain and is associated with neuropsychiatric disorders such as schizophrenia.
      Nevertheless, the robustness of this association as well as how CRYBB2 may
      contribute to disease-relevant phenotypes is unknown. To add further clarity to
      this issue, we performed a comprehensive analysis of behavioral and
      neurohistological alterations in mice with an allelic series of mutations in the
      C-terminal end of the Crybb2 gene. Behavioral phenotyping of these three betaB2
      mutant lines Crybb2O377, Crybb2Philly, and Crybb2Aey2 included assessment of
      exploratory activity and anxiety-related behavior in the open field, sensorimotor
      gating measured by prepulse inhibition (PPI) of the acoustic startle reflex,
      cognitive performance measured by social discrimination, and spontaneous
      alternation in the Y-maze. In each mutant line, we also quantified the number of
      parvalbumin-positive (PV+) GABAergic interneurons in selected brain regions that
      express CRYBB2. While there were allele-specific differences in individual
      behaviors and affected brain areas, all three mutant lines exhibited consistent
      alterations in PPI that paralleled alterations in the PV+ cell number in the
      thalamic reticular nucleus (TRN). The direction of the PPI change mirrored that
      of the TRN PV+ cell number thereby suggesting a role for TRN PV+ cell number in
      modulating PPI. Moreover, as both altered PPI and PV+ cell number are
      schizophrenia-associated endophenotypes, our result implicates mutated Crybb2 in
      the development of this neuropsychiatric disorder.

PMID- 30291585
TI  - Inter-Laboratory Characterization of the Velocity Field in the FDA Blood Pump
      Model Using Particle Image Velocimetry (PIV).
AB  - PURPOSE: A credible computational fluid dynamics (CFD) model can play a
      meaningful role in evaluating the safety and performance of medical devices. A
      key step towards establishing model credibility is to first validate CFD models
      with benchmark experimental datasets to minimize model-form errors before
      applying the credibility assessment process to more complex medical devices.
      However, validation studies to establish benchmark datasets can be cost
      prohibitive and difficult to perform. The goal of this initiative sponsored by
      the U.S. Food and Drug Administration is to generate validation data for a
      simplified centrifugal pump that mimics blood flow characteristics commonly
      observed in ventricular assist devices. METHODS: The centrifugal blood pump model
      was made from clear acrylic and included an impeller, with four equally spaced,
      straight blades, supported by mechanical bearings. Particle Image Velocimetry
      (PIV) measurements were performed at several locations throughout the pump by
      three independent laboratories. A standard protocol was developed for the
      experiments to ensure that the flow conditions were comparable and to minimize
      systematic errors during PIV image acquisition and processing. Velocity fields
      were extracted at the pump entrance, blade passage area, back gap region, and at
      the outlet diffuser regions. A Newtonian blood analog fluid composed of sodium
      iodide, glycerin, and water was used as the working fluid. Velocity measurements
      were made for six different pump flow conditions, with the blood-equivalent flow
      rate ranging between 2.5 and 7 L/min for pump speeds of 2500 and 3500 rpm.
      RESULTS: Mean intra- and inter-laboratory variabilities in velocity were ~ 10% at
      the majority of the measurement locations inside the pump. However, the inter
      laboratory variability increased to more than ~ 30% in the exit diffuser region.
      The variability between the three laboratories for the peak velocity magnitude in
      the diffuser region ranged from 5 to 25%. The bulk velocity field near the
      impeller changed proportionally with the rotational speed but was relatively
      unaffected by the pump flow rate. In contrast, flow in the exit diffuser region
      was sensitive to both the flow rate and the rotational speed. Specifically, at
      3500 rpm, the exit jet tilted toward the inner wall of the diffuser at a flow
      rate of 2.5 L/min, but the jet tilted towards the outer wall when the flow rate
      was 7 L/min. CONCLUSIONS: Inter-laboratory experimental mean velocity data (and
      the corresponding variance) were obtained for the FDA pump model and are
      available for download at https://nciphub.org/wiki/FDA_CFD . Experimental
      datasets from the inter-laboratory characterization of benchmark flow models,
      including the blood pump model presented herein and our previous nozzle model,
      can be used for validating future CFD studies and to collaboratively develop
      guidelines on best practices for verification, validation, uncertainty
      quantification, and credibility assessment of CFD simulations in the evaluation
      of medical devices (e.g. ASME V&V 40 standards working group).

PMID- 30291586
TI  - Utilization and Perceptions of Drop-in Center Services Among Youth Experiencing
      Homelessness.
AB  - Drop-in centers offer a range of services to assist unaccompanied youth
      experiencing homelessness, but little is known about their perceptions of drop-in
      centers or use of different services. A random sample of 273 youth experiencing
      homelessness in the Los Angeles area who had ever used a drop-in center was
      surveyed. Most youth heard about local drop-in centers from peers (65.1%). They
      generally reported positive perceptions of the drop-in center environment, staff,
      and clients; overall, 57.8% were "very" or "extremely" satisfied with the
      services they had received. Nearly all youth cited basic services (e.g., food,
      showers, clothes) as a reason they went to drop-in centers; far fewer reported
      going to obtain higher-level services (e.g., case management). Perceptions and
      utilization did not differ by sexual orientation; however, non-white youth were
      more likely than Whites to use drop-in centers for certain higher-level services.
      Strategies for engaging youth in drop-in center services are discussed.

PMID- 30291587
TI  - Superior Mesenteric Artery Syndrome: a Prospective Study in a Single Institution.
AB  - BACKGROUND: Superior mesenteric artery syndrome (SMAS) is a rare cause of
      duodenal obstruction, resulting from the compression of the duodenum between
      superior mesenteric artery and aorta. This prospective registry aims to describe
      demographic, clinical, and outcome features of patients suffering from SMAS and
      to point out the indications for surgery. METHODS: Between 2008 and 2016,
      patients with chronic gastrointestinal symptoms and diagnosis of SMAS were
      included. Demographics, clinical presentation, diagnosis, and surgical outcome
      were recorded. Symptoms were investigated with a standardized questionnaire. The
      diagnosis was achieved through barium swallow, CT/MR angiography (aortomesenteric
      angle <= 22 degrees , distance <= 8 mm), endoscopy. All patients underwent
      duodenojejunostomy +/- distal duodenum resection. At follow-up, symptom score and
      barium swallow were re-evaluated. RESULTS: Thirty-nine patients (11 M/28 F,
      median age 38 years, median BMI 17.8 kg/m2) were included. Barium swallow showed
      a gastroduodenal dilation in 57% of patients, and a delayed gastroduodenal
      emptying in 38%. Median aortomesenteric angle was 11 degrees  and distance was 5
      mm. All patients underwent duodenojejunostomy, and in 32 patients, a distal
      duodenum resection was also performed. At a median follow-up of 47 months, the
      overall symptom score significantly dropped (10 vs. 32, p < 0.0001) and BMI
      increased (19.5 vs. 17.8, p < 0.0001). Barium swallow at 2 months postoperatively
      showed an improvement in terms of gastroduodenal dilation and emptying in 38% of
      patients with preoperative pathological findings. CONCLUSIONS: SMAS is a rare
      condition that should be suspected in cases of chronic, refractory upper
      digestive symptoms, particularly in females with low BMIs. Surgical treatment may
      improve symptoms and quality of life, although it is not curative in all cases.
      ClinicalTrials.gov Identifier: NCT03416647.

PMID- 30291588
TI  - The epigenetic landscape in the cardiovascular complications of diabetes.
AB  - A growing body of evidence suggests that epigenetic modifications-changes to the
      genome that do not involve changes in DNA sequence-may significantly derail
      transcriptional programs implicated in angiogenesis, oxidative stress and
      inflammation, thus fostering cardiovascular damage in patients with diabetes.
      Notably, adverse epigenetic signals acquired over the life course can be
      transmitted to the offspring, and may contribute to early cardiovascular
      phenotypes in the young generations. Hyperglycaemia and insulin resistance-key
      hallmarks of diabetes-induce an array of epigenetic modifications (i.e., DNA
      methylation, histone marks, and non-coding RNAs) which are responsible for a long
      lasting impairment of vascular and cardiac function, even after intensive
      glycemic control. Hence, unveiling the "epigenetic landscape" in patients with
      diabetes may provide a post-genomic snapshot of global cardiovascular risk, and
      may furnish the tools to design personalized, epigenetic-based therapies to
      alleviate the burden of cardiovascular disease in diabetic patients. The present
      review aims to acquaint the scientific community with the rapidly advancing field
      of epigenetics and its implications in the cardiovascular complications of
      diabetes.

PMID- 30291589
TI  - Clinical inertia, reverse clinical inertia, and medication non-adherence in type
      2 diabetes.
AB  - PURPOSE: Clinical inertia and medication non-adherence are thought to contribute
      largely to the suboptimal glycemic control in many patients with type 2 diabetes.
      The present review explores the relations between A1C targets, clinical inertia
      and medication non-adherence in type 2 diabetes. METHODS: We searched PubMed for
      English-language studies published from 2001 through June 1, 2018. We also
      manually searched the references of selected articles, reviews, meta-analyses,
      and practice guidelines. Selected articles were mutually agreed upon by the
      authors. RESULTS: Clinical inertia is the failure of clinicians to initiate or
      intensify therapy when indicated, while medication non-adherence is the failure
      of patients to start or continue therapy that a clinician has recommended.
      Although clinical inertia may occur at all stages of diabetes treatment, the
      longest delays were reported for initiation or intensification of insulin.
      Medication non-adherence to antidiabetic drugs may range from 53 to 65% at 1 year
      and may be responsible for uncontrolled A1C in about 23% of cases. Reverse
      clinical inertia can be acknowledged as the failure to reduce or change therapy
      when no longer needed or indicated. Clinical inertia and medication non-adherence
      are difficult to address: clinician-and patient-targeted educational programs,
      more connected communications between clinicians and patients, the help of other
      health professional figures (nurse, pharmacist) have been explored with mixed
      results. CONCLUSIONS: Both clinical inertia and medication non-adherence remain
      significant barriers to optimal glycemic targets in type 2 diabetes. Moreover,
      part of clinical inertia may be a way through which clinicians face current
      uncertainty in medicine, including some dissonance among therapeutic guidelines.
      Scientific associations should find an agreement about how to measure and report
      clinical inertia in clinical practice and should exhort clinicians to consider
      reverse clinical inertia as a cause of persisting inappropriate therapy in
      vulnerable patients.

PMID- 30291590
TI  - Representation of Multiple Cellular Phenotypes Within Tissue-Level Simulations of
      Cardiac Electrophysiology.
AB  - Distinct electrophysiological phenotypes are exhibited by biological cells that
      have differentiated into particular cell types. The usual approach when
      simulating the cardiac electrophysiology of tissue that includes different cell
      types is to model the different cell types as occupying spatially distinct yet
      coupled regions. Instead, we model the electrophysiology of well-mixed cells by
      using homogenisation to derive an extension to the commonly used monodomain or
      bidomain equations. These new equations permit spatial variations in the
      distribution of the different subtypes of cells and will reduce the computational
      demands of solving the governing equations. We validate the homogenisation
      computationally, and then use the new model to explain some experimental
      observations from stem cell-derived cardiomyocyte monolayers.

PMID- 30291591
TI  - A Continuum Mechanics Model of Enzyme-Based Tissue Degradation in Cancer
      Therapies.
AB  - We propose a mathematical model to describe enzyme-based tissue degradation in
      cancer therapies. The proposed model combines the poroelastic theory of mixtures
      with the transport of enzymes or drugs in the extracellular space. The effect of
      the matrix-degrading enzymes on the tissue composition and its mechanical
      response are accounted for. Numerical simulations in 1D, 2D and axisymmetric (3D)
      configurations show how an injection of matrix-degrading enzymes alters the
      porosity of a biological tissue. We eventually exhibit numerically the main
      consequences of a matrix-degrading enzyme pretreatment in the framework of
      chemotherapy: the removal of the diffusive hindrance to the penetration of
      therapeutic molecules in tumors and the reduction of interstitial fluid pressure
      which improves transcapillary transport. Both effects are consistent with
      previous biological observations.

PMID- 30291592
TI  - Real-time dual-modal vein imaging system.
AB  - PURPOSE: In this paper, we present a vein imaging system to combine reflectance
      mode visible spectrum images (VIS) with transmission mode near-infrared (NIR)
      images in real time. Clear vessel localization is achieved in this manner with
      combined NIR-VIS dual-modal imaging. METHODS: Transmission and reflectance mode
      optical instrumentation is used to combine VIS and NIR images. Two methods of
      displaying the combined images are demonstrated here. We have conducted
      experiments to determine the system's resolution, alignment accuracy, and depth
      penetration. Vein counts were taken from the hands of test subjects using the
      system and compared with vein counts taken by visual analysis. RESULTS: Results
      indicate that the system can improve vein detection in the human hand while
      detecting veins of a diameter < 0.5 mm at any working distance and of a 0.25 mm
      diameter at an optimal working distance of about 30 cm. The system has also been
      demonstrated to clearly detect silicone vessels with artificial blood of diameter
      2, 1, and 0.5 mm diameter under a tissue depth of 3 mm. In a study involving 25
      human subjects, we have demonstrated that vein visibility was significantly
      increased using our system. CONCLUSIONS: The results indicate that the device is
      a high-resolution solution to near-surface venous imaging. This technology can be
      applied for IV placement, morphological analysis for disease state detection, and
      biometric analysis.

PMID- 30291593
TI  - The role of semantic transparency in visual word recognition of compound words: A
      megastudy approach.
AB  - Previous studies on visual word recognition of compound words have provided
      evidence for the influence of lexical properties (e.g., length, frequency) and
      semantic transparency (the degree of relatedness in meaning between a compound
      word and its constituents) in morphological processing (e.g., to what extent is
      doorbell influenced by door and bell?). However, a number of questions in this
      domain, which are difficult to address with the available methodological
      resources, are still unresolved. We collected semantic transparency scores for
      2,861 compound words at the constituent level (i.e., how strongly the overall
      meaning of a compound word is related to that of each constituent) and analyzed
      their effects on speeded pronunciation and lexical decision performance for the
      compound words using the English Lexicon Project ( http://elexicon.wustl.edu )
      data. The results from both tasks indicated that our human-judged semantic
      transparency ratings for both the first and second constituents play a
      significant role in compound word processing. Moreover, additional analyses
      indicated that the human-judged semantic transparency scores at the constituent
      level accounted for more variance in compound word recognition performance than
      did either whole-word semantic transparency scores or corpus-based semantic
      distance scores.

PMID- 30291594
TI  - Hepatic arterialization can predict the development of collateral veins in
      patients with HCV-related liver disease.
AB  - PURPOSE: Arrival time parametric imaging (At-PI) using contrast-enhanced
      ultrasonography (CEUS) is a procedure for evaluating liver disease progression in
      chronic hepatitis C infection (CHC). We investigated At-PI diagnostic efficacy in
      predicting development of collateral veins. METHODS: In total, 171 CHC patients
      underwent CEUS and upper gastrointestinal (UGI) endoscopy before liver biopsy.
      Conventional US was performed before CEUS to identify paraumbilical veins (PV) or
      splenorenal shunts (SRS). After intravenous perflubutane, contrast dynamics of
      liver segments 5-6 and the right kidney were saved as raw data. At-PI image ratio
      of red (ROR) pixels to the entire liver was analyzed. Receiver operating
      characteristic (ROC) curves were generated to investigate the utility of At-PI
      for collateral vein identification. RESULTS: Conventional US revealed PV in two
      patients and SRS in five patients; UGI endoscopy detected esophageal varices (EV)
      in eight patients. Diagnostic capability of At-PI for detecting PV, SRS, and EV
      was satisfactory, and high for PV and SRS [PV; area under the ROC curve (AUROC)
      0.929, cutoff value 77.9%, SRS; AUROC 0.970, cutoff value 82.0%, EV; AUROC 0.883,
      cutoff value 66.9%]. CONCLUSIONS: Evaluation of hepatic arterialization by At-PI
      was useful for predicting collateral vein development in CHC patients.

PMID- 30291595
TI  - Comment on "Proton Pump Inhibitor Use and Risk of Developing Alzheimer's Disease
      or Vascular Dementia: A Case-Control Analysis".

PMID- 30291596
TI  - Authors' Reply to Katsuhiro Toda's Comment on "Proton Pump Inhibitor Use and Risk
      of Developing Alzheimer's Disease or Vascular Dementia: A Case-Control Analysis".

PMID- 30291597
TI  - Female Nonheterosexuality Is Associated with Both "Fast" and "Slow" Male-Typical
      Strategies: Implications for Evolutionary Scenarios.

PMID- 30291598
TI  - Sexual Behavior Mediates the Relationship Between Sexual Approach Motives and
      Sexual Outcomes: A Dyadic Daily Diary Study.
AB  - Recent studies show that sexual approach (SA) motives, i.e., having sex to
      achieve a positive state such as sexual pleasure, are associated with higher
      sexual and relationship satisfaction. However, mechanisms linking SA motives to
      these outcomes are poorly understood, and the important distinction between SA
      motives that are self-directed (e.g., self-gratification) and other-directed
      (e.g., pleasing one's partner) has received little empirical attention,
      particularly in the everyday context of couples' sexuality. The present study
      focused, at an event level, on the associations between self-directed and other
      directed SA motives, and sexual satisfaction and perceived partner responsiveness
      (PPR, an aspect of relationship intimacy). We also examined the mediating role of
      the couple's sexual behavior in these associations. Data were collected over a
      month-long daily diary study involving 35 newlywed heterosexual couples and
      analyzed using the Actor-Partner Interdependence Model. Results showed that men
      and women's self-directed SA motives were associated with their own higher sexual
      satisfaction and, in men, with their female partners' sexual satisfaction as
      well. For both men and women, these associations were mediated by sexual
      behavior: Self-directed SA motives were associated with more genitally focused
      sexual behavior (e.g., vaginal intercourse, oral sex), in turn associated with
      higher sexual satisfaction. For men, other-directed SA motives were associated
      with their own greater PPR and with that of their female partners. For women,
      self-directed SA motives were associated with their own greater PPR and with that
      of their male partners. Sexual behavior did not mediate associations with PPR.
      Theoretically, these findings support dyadic models of sexual satisfaction and
      intimacy and indicate that self-directed SA motives may be more important to
      sexual satisfaction than other-directed motives. Clinically, they support sex
      therapy approaches that integrate both partners and suggest that sexual motives
      and behavior may be relevant targets for intervention.

PMID- 30291599
TI  - Gender Identity and Sexual Function in 46,XX Patients with Congenital Adrenal
      Hyperplasia Raised as Males.
AB  - In individuals with congenital adrenal hyperplasia (CAH) and 46,XX karyotype,
      androgens produced by the adrenal glands during the intrauterine development
      promote virilization of the genitals, which may even result in the development of
      a well-formed penis. Some of these children with late diagnosis are registered as
      males after birth. After obtaining approval from the internal review board, we
      evaluated gender identity and sexual function in four 46,XX severely virilized
      patients with CAH, who were originally registered and raised as males, assisted
      in our Disorders of Sexual Development Clinic. The evaluation consisted of
      questionnaires to assess gender identity and sexual activity and interview with
      the multidisciplinary team that provides care for these patients. The patients
      underwent surgery to remove uterus, ovaries, and remaining vaginal structures, in
      addition to implantation of testicular prosthesis and correction of hypospadias,
      when necessary. All four patients have developed a clear male gender identity,
      and when evaluated for sexual activity, they have reported having erections,
      libido, orgasms, and sexual attraction to women only. Two of these 4 patients had
      satisfactory sexual intercourses when assessed using the International Index of
      Erectile Function questionnaire. The other two patients who never had sexual
      intercourse reported not having a partner for sexual activity; one is 18 years
      old, and the other is 14 years old. This study showed that this group of 46,XX
      severely virilized patients with CAH, registered and raised as males, adapted
      well to the assigned male gender, with satisfactory sexual function in patients
      who had sexual intercourse.

PMID- 30291600
TI  - Interactions Between Direct and Structural Violence in Sexual Harassment Against
      Spanish and Unauthorized Migrant Women.
AB  - This article analyzes the intersection of direct and indirect violence against
      Spanish women and unauthorized migrant women working in precarious jobs in
      Almeria (Spain). Specifically, it seeks to understand how unauthorized migrant
      women define violence, the relationship between sexual harassment and other types
      of direct violence (such as intimate partner violence), and structural, legal,
      and cultural violence. To do this, we apply a multilevel intersectional analysis
      focusing on 32 interviews with Spanish and unauthorized migrant women. Three
      levels of intersectionality are shown. In the first, the interviewees do not
      label verbal abuse as sexual harassment. They attribute the abuse to their work.
      In the second, sexual harassment seems to be tied to "respect" and not "love,"
      which explains why sexual harassment has less devastating consequences for women
      than intimate partner violence. In the third, experiences of sexual harassment
      differ between Spanish women and unauthorized migrant women, and a combination of
      sexual harassment and xenophobic and racist behavior occasionally appeared.

PMID- 30291602
TI  - Screening for Adverse Drug Events: a Randomized Trial of Automated Calls Coupled
      with Phone-Based Pharmacist Counseling.
AB  - BACKGROUND: Medication adverse events are important and common yet are often not
      identified by clinicians. We evaluated an automated telephone surveillance system
      coupled with transfer to a live pharmacist to screen potentially drug-related
      symptoms after newly starting medications for four common primary care
      conditions: hypertension, diabetes, depression, and insomnia. METHODS: Cluster
      randomized trial with automated calls to eligible patients at 1 and 4 months
      after starting target drugs from intervention primary care clinics compared to
      propensity-matched patients from control clinics. Primary and secondary outcomes
      were physician documentation of any adverse effects associated with newly
      prescribed target medication, and whether the medication was discontinued and, if
      yes, whether the reason for stopping was an adverse effect. RESULTS: Of 4876
      eligible intervention clinic patients who were contacted using automated calls,
      776 (15.1%) responded and participated in the automated call. Based on positive
      symptom responses or request to speak to a pharmacist, 320 patients were
      transferred to the pharmacist and discussed 1021 potentially drug-related
      symptoms. Of these, 188 (18.5%) were assessed as probably and 479 (47.1%) as
      possibly related to the medication. Compared to a propensity-matched cohort of
      control clinic patients, intervention patients were significantly more likely to
      have adverse effects documented in the medical record by a physician (277 vs. 164
      adverse effects, p < 0.0001, and 177 vs. 122 patients discontinued with
      documented adverse effects, p < 0.0001). DISCUSSION: Systematic automated
      telephone outreach monitoring coupled with real-time phone referral to a
      pharmacist identified a substantial number of previously unidentified potentially
      drug-related symptoms, many of which were validated as probably or possibly
      related to the drug by the pharmacist or their physicians. Multiple challenges
      were encountered using the interactive voice response (IVR) automated calling
      system, suggesting that other approaches may need to be considered and evaluated.
      TRIAL REGISTRATION: ClinicalTrials.gov : NCT02087293.

PMID- 30291603
TI  - Community Health Centers Could Provide Better Outsourced Primary Care for
      Veterans.
AB  - The "VA Mission Act of 2018" will expand the current "Choice Program" legislation
      of 2014, which has enabled outsourcing of VA care to private physicians. As the
      ranks of Veteran patients swell, Congress intended that the Mission Act will help
      relieve the VHA's significant access problems. We contend that this new
      legislation will have negative consequences for veterans by diverting support
      from our VA system of 1300 hospitals and clinics. We recommend modification of
      this legislation, promoting much greater utilization of Community Health Centers
      (CHCs) for veterans outsourced primary care. In support of this proposal, we
      describe (1) features of the "VA Mission Act" relevant to outsourcing, (2) the
      challenges of the present "Choice Program" and likely future obstacles with the
      new legislation, and (3) the advantages of expanding CHC VA outsourced primary
      care. This policy would focus more on providing specialized care for veterans in
      the VA system, while coordinating with CHCs for the necessary expanded
      outsourced, holistic primary care. We conclude that failure to develop an
      incremental, cost-effective alternative as described herein represents a
      potential threat to adequate future support of our VA hospital system, and thus
      outstanding care for our veterans.

PMID- 30291604
TI  - Patient Activation Changes as a Potential Signal for Changes in Health Care
      Costs: Cohort Study of US High-Cost Patients.
AB  - BACKGROUND: Programs to improve quality of care and lower costs for the highest
      utilizers of health services are proliferating, yet such programs have difficulty
      demonstrating cost savings. OBJECTIVE: In this study, we explore the degree to
      which changes in Patient Activation Measure (PAM) levels predict health care
      costs among high-risk patients. PARTICIPANTS: De-identified claims, demographic
      data, and serial PAM scores were analyzed on 2155 patients from multiple medical
      groups engaged in an existing Center for Medicare and Medicaid Innovation-funded
      intervention over 3 years designed to activate and improve care coordination for
      high-risk patients. DESIGN: In this prospective cohort study, four levels of PAM
      (from low to high) were used as the main predictor variable. We fit mixed linear
      models for log10 of allowed charges in follow-up periods in relation to change in
      PAM, controlling for baseline PAM, baseline costs, age, sex, income, and baseline
      risk score. MAIN MEASURES: Total allowed charges were derived from claims data
      for the cohort. PAM scores were from a separate database managed by the local
      practices. KEY RESULTS: A single PAM level increase was associated with 8.3%
      lower follow-up costs (95% confidence interval 2.5-13.2%). CONCLUSIONS: These
      findings contribute to a growing evidence base that the change in PAM score could
      serve as an early signal indicating the impact of interventions designed for high
      cost, high-needs patients.

PMID- 30291605
TI  - Internal Medicine Physicians' Financial Relationships with Industry: An Updated
      National Estimate.

PMID- 30291606
TI  - Chitosan oligosaccharides alleviate PM2.5-induced lung inflammation in rats.
AB  - Air pollution of particulate matter (PM), especially PM2.5, has become a major
      public health problem in China. Exploration of therapeutic and preventive
      measures against PM2.5 toxicity is of practical significance. The aim of this
      study was to examine the inhibitory effects of chitosan oligosaccharides (COS) on
      PM2.5-induced lung inflammation in rats. Forty SPF (specific pathogen-free) male
      Wistar rats weighing 200-220 g were randomly divided into four groups: control
      group, COS group, PM2.5 group, and PM2.5+COS group. COS was pre-administered to
      rats by gavage at a single dose of 500 mg/kg 2 h before intratracheal
      instillation of PM2.5 at a single dose of 1.2 mg/kg daily for 3 consecutive days.
      Normal saline (NS) was used as negative control. Twenty-four hours after the last
      instillation of PM2.5, rats were sacrificed and subjected to bronchoalveolar
      lavage (BAL). The BAL fluids (BALF) were collected for measurement of levels of
      total proteins, lactate dehydrogenase (LDH), interleukin-1 (IL-1beta), IL-8, and
      tumor necrosis factor-alpha (TNF-alpha) using colorimetric or ELISA kits. Levels
      of total proteins, LDH activities, and pro-inflammatory mediators including IL
      1beta, IL-8, and TNF-alpha in BALF of rats in PM2.5 group significantly increased
      in comparison with those of the control group. Pre-treatment of rats with COS
      markedly blocked PM2.5-induced increase in LDH, IL-8, and TNF-alpha levels in
      BALF. In conclusion, PM2.5 exposure induces rat lung inflammation, which could be
      ameliorated by the pre-treatment of COS.

PMID- 30291607
TI  - Magnesium depletion suppresses the anti-grazer colony formation in Scenedesmus
      obliquus.
AB  - In aquatic ecosystems, many phytoplankton species have evolved various inducible
      defense mechanisms against the predation. The expression of these defenses is
      affected by environmental conditions such as nutrient availability. Here, we
      investigated the anti-grazer colony formation in Scenedesmus obliquus at
      different magnesium concentrations (0-7.3 mg L-1 Mg2+) in the presence of
      zooplankton (Daphnia)-derived infochemicals. Results showed that at adequate
      Mg2+, S. obliquus formed high proportions of multi-celled (e.g., four- and eight
      celled) colonies, resulting in significantly increased number of cells per colony
      in response to Daphnia filtrate. On the other hand, in Mg2+-deficient treatment,
      the proportion of multi-celled colonies decreased, together with reduced algal
      growth rate and photosynthetic efficiency. Finally, the treatment without Mg2+
      strongly suppressed the formation of large colony (mainly eight-celled colonies),
      whereas the algal growth rate was comparable to that in Mg2+ sufficient
      treatment. Despite the inhibition of colony formation, the time reaching the
      maximum number of cells per colony was not affected by the Mg2+ concentration,
      which generally took three days in all groups. Our results indicate that Mg2+
      deficient/absent environments significantly reduced anti-grazing colony formation
      but not the algal growth, suggesting strong dependability of this morphological
      defensive trait to magnesium fluctuation in S. obliquus.

PMID- 30291608
TI  - An event study analysis of price adjustment of refined oil and air quality in
      China.
AB  - Since marketization of the refined oil price, the Chinese government has used
      refined oil price adjustments to control air pollution. Using an event study
      analysis, we examine whether these price adjustments have impacted air quality.
      We test the abnormal returns of 12 price adjustments between 2014 and 2015 in 51
      major cities of China. The results show that the impact on air quality of refined
      oil price decreases is larger than the impact of oil price increases. Although
      results indicate air quality has deteriorated, the impact is insignificant for
      most of the cities. Consequently, we conclude that price suspension of refined
      oil has had a negligible impact on air quality. This policy is not a viable
      method to improve the air quality in the short run.

PMID- 30291609
TI  - Genotoxicity of water samples from an area of the Pampean region (Argentina)
      impacted by agricultural and livestock activities.
AB  - The aim of this study was to assess the genotoxic potential of surface waters
      located in a rural area in the north east of Buenos Aires province (Argentina)
      using the Allium cepa test. Water samples were collected at four sites located in
      a drainage channel and two sites on the Burgos stream that receives water from
      the channel, taking into account the sowing and harvesting months and rainfall
      periods. Analytical determinations revealed high total concentrations of Cd, Cu,
      Pb, and Zn (maximum values: 0.030, 0.252, 0.176, and 0.960 mg L-1, respectively),
      and concentrations of glyphosate and its metabolite aminomethylphosphonic acid
      (AMPA), with maximum values of 13.6 and 9.75 MUg L-1, respectively. Statistically
      positive correlations were observed between the total metal concentrations and
      precipitation. No cytotoxicity (mitotic index MI) was observed in A. cepa.
      However, several water samples showed significant increases in micronucleus (MN)
      frequencies with respect to the controls. No correlations were observed between
      MN and the abiotic variables or precipitation. These results showed a state of
      deterioration in the water quality at the rural area studied in Buenos Aires
      province, and heavy metal contamination may contribute to the genotoxic activity.
      A. cepa was shown to be a useful tool for the detection of genotoxicity in water
      samples from areas with agricultural and livestock activities.

PMID- 30291610
TI  - Study on dynamic adsorption of p-nitrophenol by multi-walled carbon nanotubes
      dispersed cyclodextrin.
AB  - In this paper, the modified multi-walled carbon nanotubes were prepared by beta
      cyclodextrin denoted as beta-CD-MWNTs. The structure and morphology of beta-CD
      MWNTs was characterized by TEM and the dynamic adsorption of p-nitrophenol on
      beta-CD-MWNTs was studied by the Thomas model. Some affecting factors of dynamic
      adsorption and the adsorbent regeneration process such as the sewage
      concentration, the amount of absorbent in column, including the type of reagent,
      solid-liquid ratio, regeneration time, and regeneration times were investigated
      and optimized. The results indicated that the p-nitrophenol removal rate could
      reach 84% under stuffing 2 g beta-CD-MWNTs. The curves of p-nitrophenol's dynamic
      adsorption conformed to the Thomas model. Moreover, the adsorption capacity of
      regenerated beta-CD-MWNTs was similar to the fresh beta-CD-MWNT column. The
      optimal conditions of regenerations of beta-CD-MWNTs were shown as follows: the
      type of reagent is anhydrous ethanol, the solid-liquid ratio is 200:40 (mg/mL)
      and the regeneration time is 120 min.

PMID- 30291611
TI  - Coffee waste, vector control, and dengue.

PMID- 30291613
TI  - Letter to the editor re: Cheng, YH., Chou, WC., Yang, YF. et al. Environ Sci
      Pollut Res (2017). https://doi.org/10.1007/s11356-017-0875-4.

PMID- 30291612
TI  - Silver and gold nanoparticles biosynthesized by aqueous extract of burdock root,
      Arctium lappa as antimicrobial agent and catalyst for degradation of pollutants.
AB  - This study presents an efficient and facile method for biosynthesis of silver
      nanoparticles (AgNPs) and gold nanoparticles (AuNPs) using aqueous extract of
      burdock root (BR), A. lappa, and their applications. The nanoparticles were
      characterized by ultraviolet-visible spectrophotometry, X-ray diffraction,
      transmission electron microscopy, energy dispersive X-ray, thermogravimetry, and
      differential thermal analysis. AgNPs capped the BR extract (BR-AgNPs) possessed
      roughly spherical geometry with an average diameter of 21.3 nm while uneven
      geometry of AuNPs capped the BR extract (BR-AuNPs) showed multi shapes in average
      size of 24.7 nm. The BR-AgNPs strongly inhibited five tested microorganism
      strains. In particular, the nanoparticles showed excellent catalytic activity for
      the conversion of pollutants within wastewater. Pseudo-first-order rate constants
      for the degradation of 4-nitrophenol, methyl orange, and rhodamine B were
      respectively found 6.77 * 10-3, 3.70 * 10-3, and 6.07 * 10-3 s-1 for BR-AgNPs and
      6.87 * 10-3, 6.07 * 10-3, and 7.07 * 10-3 s-1 for BR-AuNPs. Graphical abstract ?.

PMID- 30291614
TI  - Removal of vanadium and palladium ions by adsorption onto magnetic chitosan
      nanoparticles.
AB  - Chitosan (CS), synthesized from chitin chemically extracted from shrimp shells,
      was used for the synthesis of magnetic chitosan nanoparticles (Fe3O4-CSN), which
      makes the adsorbent easier to separate. Fe3O4-CSN was used for the removal of
      toxic metals such as vanadium (V(V)) and palladium (Pd(II)) ions from aqueous
      solutions. Influencing factors on the adsorption process such as pH, contact
      time, adsorbent dosage, and agitation speed were investigated. A competitive
      adsorption of V(V) and Pd(II) ions for the active sites was also studied. The
      monolayer maximum adsorption capacities (Qm) of 186.6 and 192.3 mg/g were
      obtained for V(V) and Pd(II) ions, respectively. The pseudo-second-order equation
      gave the best fit for the kinetic data, implying that chemisorption was the
      determining step. Freundlich model yielded a much better fit than the other
      adsorption models assessed (Langmuir, Temkin and Dubinin-Radushkevich). Thus, the
      adsorption of V(V) and Pd(II) ions onto Fe3O4-CSN is a combination of physical
      and chemical adsorption, as based on the kinetics and equilibrium study.
      Generally, physical adsorption is the mechanism that governs the system, while
      chemical adsorption is the slowest adsorption step that takes place.
      Thermodynamic studies displayed that the adsorption process was exothermic and
      spontaneous. Removal efficiencies of 99.9% for V(V) and 92.3% for Pd(II) ions
      were achieved, implying that Fe3O4-CSN adsorbent had an excellent ability for the
      removal of the metal ions from real industrial wastewaters without remarkable
      matrix effect. Graphical abstract ?.

PMID- 30291615
TI  - A response surface methodology for optimization of 2,4-dichlorophenoxyacetic acid
      removal from synthetic and drainage water: a comparative study.
AB  - The potential of a granular activated carbon (GAC), a rice husk biochar (BRH),
      and multi-walled carbon nanotubes (MWCNTs) for removing 2,4-dichlorophenoxyacetic
      acid (2,4-D) from simulated wastewater and drainage water has been evaluated. In
      this regard, a response surface methodology (RSM) with a central composite design
      (CCD) (CCD-RSM design) was used to optimize the removal of 2,4-D from simulated
      wastewater under different operational parameters. The maximum adsorption
      capacities followed the order GAC > BRH > MWCNTs, whereas the equilibrium time
      increased in the order MWCNTs < GAC < BRH. In the case of GAC and BRH, the 2,4-D
      removal percentage increased significantly upon increasing the adsorbent dosage
      and temperature and decreased upon increasing the initial 2,4-D concentration and
      pH. The results showed that the contact time and temperature were not important
      as regards the adsorption efficiency of 2,4-D by MWCNTs, whereas rapid removal of
      2,4-D from simulated wastewater was achieved within the first 5 min of contact
      with the MWCNTs. The results confirmed that the Freundlich isotherm model with
      the highest coefficient of determination (R2) and the lowest standard error of
      the estimate (SEE) satisfactorily fitted the 2,4-D experimental data. In
      addition, successful usage of the three adsorbents investigated was observed for
      removal of 2,4-D from drainage water from an agricultural drainage system. An
      economic analysis with a rate of return (ROR) method indicated that BRH could be
      used as an eco-friendly, low-cost, versatile, and high adsorption capacity
      alternative to GAC and MWCNTs for the removal of 2,4-D.

PMID- 30291616
TI  - Synthesis of coal fly ash zeolite for the catalytic wet peroxide oxidation of
      Orange II.
AB  - Fly ash, a coal combustion residue produced by Termotasajero in Colombia, has
      been hydrothermally treated after an alkaline fusion to produce zeolite without
      addition of silicon or aluminum. The starting material was thoroughly mixed with
      NaOH, in a 1:1.2 mass ratio, to obtain a homogeneous mixture that was heated to
      100  degrees C during different times (6, 8, and 10 h) and three zeolite samples
      were produced. The samples were characterized by XRD, SEM, XRF, Mossbauer
      spectroscopy, and N2 physisorption. According to characterization results (high
      surface area and appropriate morphological properties including crystallinity)
      and synthesis time, zeolitic catalyst synthesized with 8 h of hydrothermal
      treatment was selected to perform further analysis. This sample consisted of a
      mixture of zeolite X and zeolite A of high surface area (301 m2 g-1) and a Fe
      content of 6% wt/wt. The zeolite was used as a catalyst for the Fenton oxidation
      of Orange II. Experiments were performed in a laboratory batch reactor at 70 
      degrees C and constant pH = 3, using different concentrations of H2O2. When the
      stoichiometric amount of H2O2 was used, good mineralization (XTOC = 45%),
      complete discoloration, and oxidant consumption were obtained after 240 min of
      reaction. The sample retained activity after 16 h of usage. The presence of Fe in
      the reaction media was always detected and a homogeneous Fenton mechanism induced
      by surface-leached iron is suggested.

PMID- 30291618
TI  - 'Tis Easier.

PMID- 30291619
TI  - Reviewer Appreciation December 2018.

PMID- 30291617
TI  - Transcriptome analysis reveals the molecular response to cadmium toxicity in P.
      pseudoannulata.
AB  - Cadmium (Cd) can be transferred and accumulated in spiders, posing a survival
      risk to them. To analyze potential biological damage caused by Cd accumulation
      and relevant detoxification strategies employed by spiders in response to Cd
      exposure, we conducted transcriptome analysis of the 5th instar spider P.
      pseudoannulata, a common spider species playing a vital role in natural pest
      control in agricultural fields of southern China. We obtained 92,778 unigenes
      with an average length of 1104 bp and identified 302, 655, and 424 differentially
      expressed genes (DEGs) in the spiders fed with Cd-containing fruit flies for 2,
      5, and 8 days, respectively. Results showed that the body mass of Cd-containing
      P. pseudoannulata were reduced when compared with controls, presumably due to
      delayed maturation of tissues and organs. Meanwhile, functional analysis of DEGs
      indicated that Cd may have a negative effect on neural signal transduction and
      molt cycle of the spider. For defense strategies, detoxification enzymes like
      glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and
      P450, and typical proteins like heat shock protein and metallothionein were all
      differentially expressed in response to Cd stress. Besides, innate immune
      responses like toll-like receptor signaling pathways were also upregulated.
      Multiple critical Cd-responsive genes involved in biological damage,
      detoxification, and immune response were identified, providing referable
      foundation for further research on Cd toxicity to P. pseudoannulata.

PMID- 30291620
TI  - It Happened Here: Debriefing Groups to Help Psychiatry Residents Process
      Traumatic Community Events.

PMID- 30291621
TI  - Canine cognition.

PMID- 30291622
TI  - gammadelta T cells amplify Blomia tropicalis-induced allergic airway disease.

PMID- 30291623
TI  - Sex-biased hippocampal pathology in the 5XFAD mouse model of Alzheimer's disease:
      A multi-omic analysis.
AB  - Alzheimer's disease is a progressive neurodegenerative disorder and the most
      common form of dementia. Like many neurological disorders, Alzheimer's disease
      has a sex-biased epidemiological profile, affecting approximately twice as many
      women as men. The cause of this sex difference has yet to be elucidated. To
      identify molecular correlates of this sex bias, we investigated molecular
      pathology in females and males using the 5XFamilial Alzheimer's disease mutations
      (5XFAD) genetic mouse model of Alzheimer's disease. We profiled the transcriptome
      and proteome of the mouse hippocampus during early stages of disease development
      (1, 2, and 4 months of age). Our analysis reveals 42 genes that are
      differentially expressed between disease and wild-type animals at 2 months of
      age, prior to observable plaque deposition. In 4-month-old animals, we detect
      1,316 differentially expressed transcripts between transgenic and control 5XFAD
      mice, many of which are associated with immune function. Additionally, we find
      that some of these transcriptional perturbations are correlated with altered
      protein levels in 4-month-old transgenic animals. Importantly, our data indicate
      that female 5XFAD mouse exhibit more profound pathology than their male
      counterparts as measured by differences in gene expression. We also find that the
      5XFAD transgenes are more highly expressed in female 5XFAD mice than their male
      counterparts, which could partially account for the sex-biased molecular
      pathology observed in this dataset.

PMID- 30291624
TI  - The neurobiology of impulsivity and substance use disorders: implications for
      treatment.
AB  - Impulsivity is strongly associated with substance use disorders (SUDs). Our
      review discusses impulsivity as an underlying vulnerability marker for SUDs, and
      treatment of co-occurring impulsivity in SUDs. Three factors should be considered
      for the complex relationship between impulsivity and a SUD: (1) the trait effect
      of impulsivity, centering on decreased cognitive and response inhibition, (2) the
      state effect resulting from either acute or chronic substance use on brain
      structure and function, and (3) the genetic and environmental factors (e.g., age
      and sex) may influence impulsive behavior associated with SUDs. Both subjective
      and objective measures are used to assess impulsivity. Together, treatment
      developments (pharmacological, behavioral, and neurophysiological) should
      consider these clinically relevant dimensions assessed by a variety of measures,
      which have implications for treatment matching in individuals with SUD. Despite
      its heterogeneity, impulsivity is a marker associated with SUDs and may be
      understood as an imbalance of bottom-up and top-down neural systems. Further
      investigation of these relationships may lead to more effective SUD treatments.

PMID- 30291625
TI  - Clinical factors predicting treatment resistant depression: affirmative results
      from the European multicenter study.
AB  - OBJECTIVES: Clinical variables were investigated in the 'treatment resistant
      depression (TRD)- III' sample to replicate earlier findings by the European
      research consortium 'Group for the Study of Resistant Depression' (GSRD) and
      enable cross-sample prediction of treatment outcome in TRD. EXPERIMENTAL
      PROCEDURES: TRD was defined by a Montgomery and Asberg Depression Rating Scale
      (MADRS) score >=22 after at least two antidepressive trials. Response was defined
      by a decline in MADRS score by >=50% and below a threshold of 22. Logistic
      regression was applied to replicate predictors for TRD among 16 clinical
      variables in 916 patients. Elastic net regression was applied for prediction of
      treatment outcome. RESULTS: Symptom severity (odds ratio (OR) = 3.31), psychotic
      symptoms (OR = 2.52), suicidal risk (OR = 1.74), generalized anxiety disorder (OR
      = 1.68), inpatient status (OR = 1.65), higher number of antidepressants
      administered previously (OR = 1.23), and lifetime depressive episodes (OR = 1.15)
      as well as longer duration of the current episode (OR = 1.022) increased the risk
      of TRD. Prediction of TRD reached an accuracy of 0.86 in the independent
      validation set, TRD-I. CONCLUSION: Symptom severity, suicidal risk, higher number
      of lifetime depressive episodes, and comorbid anxiety disorder were replicated as
      the most prominent risk factors for TRD. Significant predictors in TRD-III
      enabled robust prediction of treatment outcome in TRD-I.

PMID- 30291626
TI  - Aged human skin accumulates mast cells with altered functionality that localize
      to macrophages and vasoactive intestinal peptide-positive nerve fibres.
AB  - BACKGROUND: Skin health declines with age and this is partially attributed to
      immunosenescence. Mast cells (MCs) are innate immune cells that coordinate tissue
      immune responses integral to skin homeostasis and disease. OBJECTIVES: To
      understand how MCs contribute to human skin ageing, we investigated how intrinsic
      ageing impacts MC phenotype and MC relationships with other immune cells and skin
      structures. METHODS: In photoprotected skin biopsies from young (<= 30 years) and
      aged (>= 75 years) individuals, immunostaining and spatial morphometry were
      performed to identify changes in MC phenotype, number, distribution and
      interaction with the vasculature and nerve fibres. Quantitative polymerase chain
      reaction was used to measure changes in gene expression related to immune cell
      activity and neuropeptide signalling. RESULTS: Skin MCs, macrophages and CD8+ T
      cells increased in number in intrinsically aged vs. young skin by 40%, 44% and
      90%, respectively (P < 0.05), while CD4+ T cells and neutrophils were unchanged.
      In aged skin, MCs were more numerous in the papillary dermis and showed a reduced
      incidence of degranulation (50% lower than in young, P < 0.01), a conserved
      tryptase-chymase phenotype and coexpression of granzyme B. In aged skin, MCs
      increased their association with macrophages (~ 48% vs. ~27%, P < 0.05) and nerve
      fibres (~29% vs. 16%, P < 0.001), while reducing their interactions with blood
      vessels (~34% vs. 45%, P < 0.001). Additionally, we observed modulation of gene
      expression of vasoactive intestinal peptide (VIP; increased) and substance P
      (decreased) with age; this was associated with an increased frequency of VIP+
      nerve fibres (around three times higher in aged skin, P < 0.05), which were
      strongly associated with MCs (~19% in aged vs. 8% in young, P < 0.05).
      CONCLUSIONS: In photoprotected skin we observed an accumulation of MCs with
      increasing age. These MCs have both altered functionality and distribution within
      the skin, which supports a role for these cells in altered tissue homeostasis
      during ageing.

PMID- 30291627
TI  - Risk of excessive intake of vitamins and minerals delivered through public health
      interventions: objectives, results, conclusions of the meeting, and the way
      forward.
AB  - The excessive consumption of certain vitamins and minerals could have deleterious
      consequences on health and development of individuals and populations.
      Simultaneous micronutrient-delivery interventions could be challenging in terms
      of safety as the target populations may overlap, posing a risk of excessive
      intake of certain micronutrients. The Evidence and Programme Guidance Unit of the
      Department of Nutrition for Health and Development of the World Health
      Organization convened a technical consultation on the risk of excessive intake of
      vitamins and minerals delivered through public health interventions in October
      2017. The technical consultation's working groups identified important and
      emerging technical issues, lessons learned, and research priorities related to
      (1) planning, implementing, monitoring, and evaluating nutrition programs for the
      detection and control of the risk of excessive intakes; (2) safety, quality
      control, and assurance considerations; (3) coordination between public health
      nutrition interventions and other interventions and sectors; and (4) the
      legislative framework and policy coherence needed for simultaneous nutrition
      interventions. This paper provides the background and rationale of the technical
      consultation, synopsizes the presentations, and provides a summary of the main
      considerations proposed by the working groups.

PMID- 30291628
TI  - Historical weather data for climate risk assessment.
AB  - Weather- and climate-related hazards are responsible for monetary losses,
      material damages, and societal consequences. Quantifying related risks is,
      therefore, an important societal task, particularly in view of future climate
      change. For this task, climate risk assessment increasingly uses model chains,
      which mainly build on data from the last few decades. The past record of events
      could play a role in this context. New numerical techniques can make use of
      historical weather data to simulate impacts quantitatively. However, using
      historical data for model applications differs from using recent products. Here,
      we provide an overview of climate risk assessment methodologies and of the
      properties of historical instrumental and documentary data. Using three examples,
      we then outline how historical environmental data can be used today in climate
      risk assessment by (1) developing and validating numerical model chains, (2)
      providing a large statistical sample which can be directly exploited to estimate
      hazards and to model present risks, and (3) establishing "worst-case" events
      which are relevant references in the present or future. The examples show that,
      in order to be successful, different sources (reanalyses, digitized instrumental
      data, and documentary data) and methods (dynamical downscaling and analog
      methods) need to be combined on a case-by-case basis.

PMID- 30291629
TI  - Analysis of catalase mutants underscores the essential role of CATALASE2 for
      plant growth and day length-dependent oxidative signalling.
AB  - Three genes encode catalase in Arabidopsis. Although the role of CAT2 in
      photorespiration is well established, the importance of the different catalases
      in other processes is less clear. Analysis of cat1, cat2, cat3, cat1 cat2, and
      cat2 cat3 T-DNA mutants revealed that cat2 had the largest effect on activity in
      both roots and leaves. Root growth was inhibited in all cat2-containing lines,
      but this inhibition was prevented by growing plants at high CO2 , suggesting that
      it is mainly an indirect effect of stress at the leaf level. Analysis of double
      mutants suggested some overlap between CAT2 and CAT3 functions in leaves and CAT1
      and CAT2 in seeds. When plants had been grown to a similar developmental stage in
      short days or long days, equal-time exposure to oxidative stress caused by
      genetic or pharmacological inhibition of catalase produced a much stronger
      induction of H2 O2 marker genes in short day plants. Together, our data (a)
      underline the importance of CAT2 in basal H2 O2 processing in Arabidopsis; (b)
      suggest that CAT1 and CAT3 are mainly "backup" or stress-specific enzymes; and
      (c) establish that day length-dependent responses to catalase deficiency are
      independent of the duration of oxidative stress.

PMID- 30291630
TI  - The IMF failure that wasn't: risk ignorance during the European debt crisis.
AB  - This article builds on ignorance studies to revisit how we understand the role of
      expertise in international policymaking. A fundamental component of ignorance is
      concealing what you know. For experts, risk ignorance is a strategic resource
      when the policymaking process becomes a contested exchange. This article covers
      IMF lending programmes in Europe in 2008-13 with a special focus on Greece.
      Empirical data is drawn from policy documents. I find that risk ignorance at the
      IMF resulted from a joint process of 'private alteration' and 'public
      obfuscation': the alteration of normal scenarios of debt sustainability in
      private negotiations worked in tandem with the obfuscation of programme risks in
      the public stage. The empirical contribution of this article is to show that the
      'failure' of the IMF programme for Greece can be reconceptualized as 'success'.
      The immediate goal of the programme was to bailout Greece's creditors and avoid
      the breakup of European monetary institutions. In this respect, the programme was
      successful. But success came at a huge cost for Greece. Analytically, this
      article suggests that knowledge procurement based on empirical fact-gathering is
      not always the ultimate goal of international organizations and the communities
      of experts working within them.

PMID- 30291632
TI  - Seasonal changes in neuronal turnover in a forebrain nucleus in adult songbirds.
AB  - Neuronal death and replacement, or neuronal turnover, in the adult brain are one
      of many fundamental processes of neural plasticity. The adult avian song control
      circuit provides an excellent model for exploring mature neuronal death and
      replacement by new neurons. In the song control nucleus, HVC of adult male
      Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelli) nearly 68,000
      neurons are added each breeding season and die during the subsequent nonbreeding
      season. To accommodate large seasonal differences in HVC neuron number, the
      balance between neuronal addition and death in HVC must differ between seasons.
      To determine whether maintenance of new HVC neurons changes within and between
      breeding and nonbreeding conditions, we pulse-labeled two different cohorts of
      new HVC neurons under both conditions and quantified their maintenance. We show
      that the maintenance of new HVC neurons, as well as new nonneuronal cells, was
      higher at the onset of breeding conditions than at the onset of nonbreeding
      conditions. Once a steady-state HVC volume and neuronal number were attained in
      either breeding or nonbreeding conditions, neuronal and nonneuronal maintenance
      were similarly low. We found that new neuronal number correlated with a new
      nonneuronal number within each cohort of new neurons. Together, these data
      suggest that sex steroids promote the survival of an initial population of new
      neurons and nonneuronal cells entering HVC. However, once HVC is fully grown or
      regressed, neuronal and nonneuronal cell turnover is regulated by a common
      mechanism likely independent of direct sex steroid signaling.

PMID- 30291633
TI  - Neurostimulation for the treatment of chronic migraine and cluster headache.
AB  - Small subsets of patients who fail to respond to pharmacological treatment may
      benefit from alternative treatment methods. In the last decade, neurostimulation
      is being explored as a potential treatment option for the patients with chronic,
      severely disabling refractory primary headaches. To alleviate pain, specific
      nerves and brain areas have been stimulated, and various methods have been
      explored: deep brain stimulation, occipital nerve stimulation, and sphenopalatine
      ganglion stimulation are among the more invasive ones, whereas transcranial
      magnetic stimulation and supraorbital nerve stimulation are noninvasive. Vagal
      nerve stimulation can be invasive or noninvasive, though this review included
      only data for noninvasive VNS. Most of these methods have been tested in small
      open-label patient series; recently, more data from randomized, controlled, and
      blinded studies are available. Although neurostimulation treatments have
      demonstrated good efficacy in many studies, it still has not been established as
      a standard treatment in refractory patients. This review analyzes the available
      evidence regarding efficacy and safety of different neurostimulation modalities
      for the treatment of chronic migraine and cluster headache.

PMID- 30291634
TI  - Facebook use and sleep quality: Light interacts with socially induced alertness.
AB  - It has been demonstrated that the use of social networking sites late at night
      can lead to sleep-related problems that extend into the next day. A common
      explanation is that the light emitted from screens is disrupting the users'
      circadian rhythms. An alternative explanation is that the social cognition
      inherent in the use of social networking sites is responsible. Here, the two
      factors were looked at together. Participants used Facebook on iPad tablets
      before sleep. This was done on different nights with two lighting conditions and
      with two levels of content. In the 'light' condition, blue wavelength light was
      manipulated so that it was either full wavelength or blue light filtered. In the
      'alertness' condition, the personal significance of the content was changed from
      personally relevant to irrelevant. A modified version of the Pittsburgh Sleep
      Quality Index was used to measure sleep-related problems. No evidence was found
      that simply filtering blue light or simply removing relevant content improved
      sleep quality. However, the two factors interacted. The results suggest that the
      light emitted from screens can affect sleep quality under some conditions but
      this is behaviourally irrelevant in the context of normal Facebook usage.

PMID- 30291635
TI  - Ice segregation in the crown of winter cereals: Evidence for extraorgan and
      extratissue freezing.
AB  - Meaningful improvements in winter cereal cold hardiness requires a complete model
      of freezing behaviour in the critical crown organ. Magnetic resonance
      microimaging diffusion-weighted experiments provided evidence that cold
      acclimation decreased water content and mobility in the vascular transition zone
      (VTZ) and the intermediate zone in rye (Secale cereale L. Hazlet) compared with
      wheat (Triticum aestivum L. Norstar). Differential thermal analysis, ice
      nucleation, and localization studies identified three distinct exothermic events.
      A high-temperature exotherm (-3 degrees C to -5 degrees C) corresponded with ice
      formation and high ice-nucleating activity in the leaf sheath encapsulating the
      crown. A midtemperature exotherm (-6 degrees C and -8 degrees C) corresponded
      with cavity ice formation in the VTZ but an absence of ice in the shoot apical
      meristem (SAM). A low-temperature exotherm corresponded with SAM injury and the
      killing temperature in wheat (-21 degrees C) and rye (-27 degrees C). The SAM had
      lower ice-nucleating activity and freezing survival compared with the VTZ when
      frozen in vitro. The intermediate zone was hypothesized to act as a barrier to
      ice growth into the SAM. Higher cold hardiness of rye compared with wheat was
      associated with higher VTZ and intermediate zone desiccation resulting in the
      formation of ice barriers surrounding the SAM.

PMID- 30291636
TI  - Electrodiagnostic evidence of suprascapular nerve recovery after decompression.
AB  - INTRODUCTION: The purpose of this study was to determine whether surgical
      arthroscopic decompression or ultrasound-guided aspiration of a paralabral cyst
      would result in suprascapular nerve recovery from axonal regeneration based on
      electrodiagnostic testing. METHODS: Nine patients with preoperative
      electromyography (EMG) evidence of suprascapular neuropathy due to paralabral
      cysts at the suprascapular or spinoglenoid notch were prospectively studied.
      Eight patients underwent arthroscopic surgical decompression, and 1 patient
      underwent ultrasound-guided aspiration. Postoperative EMG was performed in all
      patients to evaluate nerve regeneration. RESULTS: Three (33%) patients had cysts
      at the suprascapular notch, whereas 6 (67%) patients had cysts at the
      spinoglenoid notch. All patients showed complete electrophysiological recovery
      after decompression. DISCUSSION: Decompression of paralabral cysts at the
      suprascapular or spinoglenoid notch resulted in postoperative EMG evidence of
      nerve recovery. Long-term studies with a greater number of patients are required
      to elucidate time to recovery. Muscle Nerve, 2018.

PMID- 30291637
TI  - Response to 'Adverse effects of a single dose of gentamicin' by Halmagyi and
      Curthoys.

PMID- 30291638
TI  - Issue Highlights: October 2018.

PMID- 30291639
TI  - Ultrasound Adds No Benefit to Clinical Exam for Predicting Dehydration in
      Children With Acute Diarrhea in a Resource-Limited Setting.
AB  - OBJECTIVES: Diarrhea is one of the most common and deadly conditions affecting
      children, causing over 525,000 deaths annually, largely in resource-limited
      settings. Appropriate treatment depends on accurate determination of dehydration
      status. This study evaluated the accuracy of a new model using clinical and
      ultrasound measurements for predicting dehydration status in children with acute
      diarrhea. METHODS: The Dehydration: Assessing Kids Accurately (DHAKA) study was a
      prospective cohort study of children under 5 years of age with acute diarrhea
      presenting to the International Centre for Diarrhoeal Disease Research in Dhaka,
      Bangladesh. Clinical signs and sonographic measurements of the aorta-to-inferior
      vena cava ratio were recorded. Percent weight change with rehydration was used to
      classify dehydration severity. Logistic regression was used to create a combined
      DHAKA-US model based on clinical and sonographic measurements. Area under the
      curve and calibration slope were used to assess the model's accuracy and compare
      it to the original DHAKA score model. RESULTS: A total of 850 children were
      enrolled, with 736 included in the final analysis. The combined DHAKA-US model
      showed equivalent discrimination with the original DHAKA score, with an area
      under the curve of 0.79 for both models for severe dehydration (95% confidence
      interval, 0.74-0.84), as well as similar classification (48% versus 50% correctly
      classified) and calibration (calibration slopes of 0.900 versus 0.904 for
      presence of any dehydration). CONCLUSION: Adding sonographic measurements to the
      DHAKA score had no effect on discrimination, classification, or calibration when
      compared to the original DHAKA score. Clinical signs alone may be the most
      important predictors of dehydration status in children with diarrhea in limited
      resource settings.

PMID- 30291640
TI  - Decision rule approach applied to estimate occupational lead exposure in a case
      control study of kidney cancer.
AB  - BACKGROUND: We developed a systematic, data-driven approach to estimate metrics
      of occupational exposure to lead to aid in epidemiologic analyses in a case
      control study of kidney cancer. METHODS: Probability of exposure to ten lead
      sources was assigned using decision rules developed from an extensive literature
      review and expert judgement. For jobs with >50% probability of exposure, we
      assigned source-specific frequency based on subjects' self-reported task
      frequencies or means of subjects' job-groups and source-specific intensity
      estimates of blood lead (MUg/dL). RESULTS: In our study, 18.7% of employed person
      years were associated with high (>=80%) probability of exposure to any lead
      source. The most common medium (>50%) or high probability source of lead exposure
      was leaded gasoline (2.5% and 11.5% of employed person-years, respectively). The
      median blood lead attributed to occupational exposure was 3.1 MUg/dL.
      CONCLUSIONS: These rules can aid in future studies after population-specific
      adaption for geographic differences and different exposure scenarios.

PMID- 30291641
TI  - Longitudinal and personalized networks of eating disorder cognitions and
      behaviors: Targets for precision intervention a proof of concept study.
AB  - INTRODUCTION: Despite the high mortality and significant societal and personal
      costs associated with eating disorders (EDs) there are few evidence-based
      treatments. Part of the difficulty developing and implementing evidence-based
      treatments in EDs is due to the extremely high heterogeneity (e.g., variability
      in treatment outcome, symptom presentation etc) present. METHODS: To begin to
      identify specific symptom heterogeneity within persons, the current study used
      novel within and between group and intra-individual network analyses to create
      longitudinal and within-person networks of ED cognitions and behaviors (N = 66
      individuals diagnosed with an ED). This article provides a proof of concept study
      for how to use between and within-person network analyses both for the EDs and
      other forms of psychopathology. RESULTS: We found that cognitions focused on
      desiring thinness played a likely maintaining role in ED pathology, across
      network type and across time. Furthermore, we showed that three individuals with
      the same diagnosis (anorexia nervosa) differed in which symptoms maintained the
      disorder. We use these participants to exemplify how to use intra-individual
      network analysis to personalize treatment focused on the primary maintaining
      symptoms. Finally, we found that amount of time (e.g., 4 hr vs. simultaneously)
      impacts how symptoms maintain each other. CONCLUSIONS: These findings have
      implications for the development of novel personalized evidence-based treatments
      for EDs, as well as implications for how the field understands how
      psychopathology maintains itself. These data represent a first-step towards using
      intra-individual network analyses in the ED field, as well as for hypotheses
      generation in future research.

PMID- 30291642
TI  - Comments on Brimo F, Downes MR, Jamaspishvili T, Berman D, Barkan G, Athanazio D,
      Abro S, Visram K, Yilmaz A, Solanki S, Hahn E, Siemens R, Kassouf W, Trpkov K.
      Prognostic pathological factors in radical cystectomy after neoadjuvant
      chemotherapy. Histopathology 2018; DOI: 10.1111/his.13654.
AB  - We read with interest the report by Brimo questioning the relevance of the Tumour
      Regression-Grade (TRG) after neo-adjuvant chemotherapy (NAC) and cystectomy in
      muscle-invasive bladder cancer (MIBC). While classical prognosticators such as T
      stage, N-stage and margin status were independent predictors of survival, TRG of
      the primary tumours (TRGPT ) failed to do so. However, the informative nature of
      the TRGPT may be impacted by the influence of trans-urethral resection in the
      primary tumour. This article is protected by copyright. All rights reserved.

PMID- 30291643
TI  - High-efficient bacterial production of human ApoA-I amyloidogenic variants.
AB  - Apolipoprotein A-I (ApoA-I)-related amyloidosis is a rare disease caused by
      missense mutations in the APOA1 gene. These mutations lead to protein aggregation
      and abnormal accumulation of ApoA-I amyloid fibrils in heart, liver, kidneys,
      skin, nerves, ovaries, or testes. Consequently, the carriers are at risk of
      single- or multi-organ failure and of need of organ transplantation.
      Understanding the basic molecular structure and function of ApoA-I amyloidogenic
      variants, as well as their biological effects, is, therefore, of great interest.
      However, the intrinsic low stability of this type of proteins makes their
      overexpression and purification difficult. To overcome this barrier, we here
      describe an optimized production and purification procedure for human ApoA-I
      amyloidogenic proteins that efficiently provides between 46 mg and 91 mg
      (depending on the protein variant) of pure protein per liter of Escherichia coli
      culture. Structural integrity of the amyloidogenic and native ApoA-I proteins
      were verified by circular dichroism spectroscopy and intrinsic fluorescence
      analysis, and preserved functionality was demonstrated by use of a lipid
      clearance assay as well as by reconstitution of high-density lipoprotein (HDL)
      particles. In conclusion, the use of the described high-yield protein production
      system to obtain amyloidogenic ApoA-I proteins, and their native counterpart,
      will enable molecular and cellular experimental studies aimed to explain the
      molecular basis for this rare disease.

PMID- 30291644
TI  - Blood draws up to 3% of blood volume in clinical trials are safe in children.
AB  - AIM: Recommendations for maximum blood draw in children range from 1 to 5%
      despite limited evidence. The aim of the study was to assess the safety of blood
      draws in children aged six months to 12 years targeting volumes of 3% of total
      blood volume. METHODS: Children who experienced three-monthly blood draws during
      participation in one of three investigators initiated clinical trials conducted
      in our institution were examined. In total, 629 venous blood draws were performed
      in 141 children. Adverse events and blood counts were assessed. RESULTS: Overall,
      608 adverse events were reported. None of these included symptoms that reflected
      concerns on blood draw volumes or frequency. Anaemia and red cell or haemoglobin
      measurements outside the normal age range were not observed. A reduction in
      haemoglobin, haematocrit, mean corpuscular haemoglobin, mean corpuscular
      haemoglobin concentration and mean corpuscular volume was noted in children
      participating in one of the three trials analysed. CONCLUSION: Regular blood
      draws of up to 3% of total blood volume were not associated with signs of anaemia
      or hypovolaemia in young children. We suggest that the European recommendations
      be revised for clinical studies in which children are not exposed to treatments
      that are associated with anaemia risk.

PMID- 30291645
TI  - Isolation and Characterization of Flavobacteriaceae from Farmed and Wild Nile
      Tilapia in Tanzania.
AB  - The present study was conducted to explore the occurrence of Flavobacteriaceae in
      wild (n = 108) and farmed (n = 187) Nile Tilapia (Oreochromis niloticus)
      collected from Lake Victoria and twelve ponds in the Morogoro region,
      respectively. The size of the ponds surveyed ranged from 130 - 150 m2 . Ponds
      parameters and fish morphometric data were recorded during sampling. A total of
      67 (farmed n = 44 and wild = 23) Flavobacterium-like isolates were identified on
      the basis of colony morphology and biochemical tests. Sequences from 16S rRNA
      gene revealed that all 67 isolates belonged to the genera Flavobacterium and
      Chryseobacterium. Based on 16S rRNA nucleotide identity, 26 isolates showed high
      similarity with Chryseobacterium indologenes (99 to 100% identity), 16 to
      Chryseobacterium joostei (98 - 99.9%), 17 to diverse species of Chryseobacterium
      (97 - 99%). Three isolates were each similar to Flavobacterium aquatile and
      Flavobacterium indicum with 99 - 100% nucleotide identity respectively and 2
      isolates were similar to Flavobacterium oryzae (99 - 100%). The findings obtained
      in this study provide a baseline for future studies and contribute to an
      understanding of the threats presented by the aquatic Flavobacteriaceae reservoir
      towards the development of healthy fish farming in Tanzania. Such knowledge is
      vital for the development of sustainable aquaculture industry in Tanzania that
      will contribute to increased food security. This article is protected by
      copyright. All rights reserved.

PMID- 30291646
TI  - Ligand Radicals as Modular Organic Electron Spin Qubits.
AB  - The intrinsic redox activity of the dithiolene ligand is presented here as the
      novel spin host in the design of a prototype molecular electron spin qubit, where
      the traditional roles of the metal and ligand components in coordination
      complexes are inverted. A series of paramagnetic bis(dithiolene) complexes with
      group 10 metals-nickel, palladium, platinum-provides a backdrop to investigate
      the spin dynamics of the organic ligand radical using pulsed EPR spectroscopy.
      The temperature dependence of the phase memory time (TM ) is shown to be
      dependent on the identity of the diamagnetic metal ion, with the short times
      recorded for platinum a consequence of a diminishing spin-lattice (T1 )
      relaxation time driven by spin-orbit coupling. The utility of the radical ligand
      spin center is confirmed when it delivers one of the longest phase memory times
      ever recorded for a molecular two-qubit prototype.

PMID- 30291647
TI  - Vitamin D level affects IVF outcome partially mediated via Th/Tc cell ratio.
AB  - PROBLEM: The role of vitamin D (VD) in IVF outcome and immune parameters has not
      been elucidated well. METHOD OF STUDY: Women undergoing IVF treatment with GnRH
      agonist (Agonist) and progestin-primed ovarian stimulation (PPOS) protocols were
      divided into VD lower (VDL, 25(OH)VD <=20 ng/mL) and VD higher (VDH, 25(OH)VD >20
      ng/mL) groups. Follicular fluid (FF) VD level, IVF outcomes, and peripheral blood
      immunophenotypes by flow cytometry were analyzed. RESULTS: FF VD levels of the
      whole subjects were positively correlated with peripheral blood VD level (r =
      0.86, P < 0.001). The number of mature oocytes and the blastocyst formation rate
      were significantly higher in women with VDH group as compared with those of VDL
      group in both Agonist and PPOS groups (P < 0.05, respectively). In women with
      PPOS protocol, peripheral blood NK and B-cell proportions and T helper/T
      cytotoxic (Th/Tc) cell ratios of VDL group were significantly higher than those
      of VDH group (P < 0.05, respectively). In women with Agonist protocol, peripheral
      blood B-cell proportion and Th/Tc ratios of VDL group were significantly higher
      than those of VDH group (P < 0.05, respectively). CONCLUSION: VD level is
      associated with IVF outcomes possibly derived by T-cell immunity, particularly
      Th/Tc ratios.

PMID- 30291648
TI  - Evaluation of Effects of TGF-beta1 Inhibition on Gastric Cancer in Nude Mice by
      Diffusion Kurtosis Imaging and In-Line X-ray Phase Contrast Imaging With
      Sequential Histology.
AB  - BACKGROUND: Accurate and complete response evaluation after treatment is
      important to implement individualized therapy for gastric cancer. PURPOSE: To
      investigate the effectiveness of diffusion kurtosis imaging (DKI) and in-line X
      ray phase contrast imaging (ILXPCI) in the assessment of the therapeutic efficacy
      by transforming growth factor beta 1 (TGF-beta1) inhibition. STUDY TYPE:
      Prospective animal study. ANIMAL MODEL: Thirty nude mice subcutaneous
      xenotransplantation tumor model of gastric cancer for DKI and 10 peritoneal
      metastasis nude mice model for ILXPCI. FIELD STRENGTH/SEQUENCE: Examinations
      before and serially at 7, 14, 21, and 28 days after TGF-beta1 inhibition
      treatment were performed at 3T MRI including T2 -weighted imaging (T2 WI) and DKI
      with five b values of 0, 500, 1000, 1500, 2000 s/mm2 ; ILXPCI examinations were
      performed at 14 days after treatment. ASSESSMENT: DKI parameters (apparent
      diffusion coefficient [ADC], diffusivity [D] and kurtosis [K]) were calculated by
      two experienced radiologists after postprocessing. STATISTICAL TESTS: For the
      differences in all the parameters between the baseline and each timepoint for
      both the treated and the control mice, the Mann-Whitney test was used. The
      Spearman correlation test was used to evaluate correlations among the DKI
      parameters and corresponding pathologic necrosis fraction (NF). RESULTS: ADC, D,
      and K values were significantly different between the two groups after treatment
      (P < 0.05). Serial measurements in the treated group showed that the ADC, D, and
      K values were significantly different at 7, 14, 21, and 28 days compared with
      baseline (P < 0.05). There were significant correlations between DKI parameters
      and NF (ADC, r = 0.865, P < 0.001; D, r = 0.802, P < 0.001; K, r = -0.944, P <
      0.001). The ILXPCI results in the treated group showed a stronger absorption area
      than the control group. DATA CONCLUSION: DKI may be used to evaluate the complete
      course therapeutic effects of gastric cancer induced by TGF-beta1 inhibition, and
      the ILXPCI technique will improve the tumor microstructure resolution. LEVEL OF
      EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018.

PMID- 30291649
TI  - Prospective Evaluation of an R2* Method for Assessing Liver Iron Concentration
      (LIC) Against FerriScan: Derivation of the Calibration Curve and Characterization
      of the Nature and Source of Uncertainty in the Relationship.
AB  - BACKGROUND: FerriScan is the method-of-choice for noninvasive liver iron
      concentration (LIC) quantification. However, it has a number of drawbacks
      including cost and expediency. PURPOSE/HYPOTHESIS: To characterize an R2*-based
      MRI technique that may potentially be used as an alternative to FerriScan. This
      was accomplished through the derivation of a calibration curve that characterized
      the relationship between FerriScan-derived LIC and R2*. The nature and source of
      uncertainty in this curve were investigated. It was hypothesized that the source
      of uncertainty is heterogeneity of LIC across the liver. STUDY TYPE: Prospective.
      SUBJECTS: In all, 125 patients (69 women, 56 men) undergoing chelation treatment
      for iron overload prospectively underwent FerriScan and R2* MRI during the same
      exam. FIELD STRENGTH/SEQUENCE: Pulse sequences included 2D multislice spin-echo
      pulse for FerriScan, and a prototype 3D 6-echo gradient echo acquisition for R2*
      mapping at 1.5T. ASSESSMENT: A linear calibration curve was derived from the
      relationship between FerriScan-derived LIC estimates and R2* through least
      squares fitting. STATISTICAL TESTS: The nature of the uncertainty in the curve
      was characterized through tests of normality and homoscedasticity. The source of
      uncertainty was tested by comparing the magnitude of LIC variation over the
      FerriScan ROI to the observed uncertainty in the R2*-derived LIC estimates.
      RESULTS: A linear relationship between logarithmically transformed FerriScan
      derived LIC and R2* (log{FerriScan-derived LIC} = 1.029 log{R2*} - 3.822) was
      confirmed. Uncertainty was random, with a behaviour that was normal and
      homoscedastic. The source of uncertainty was confirmed as iron heterogeneity
      across the liver. The nontransformed calibration curve was: FerriScan-derived LIC
      = 0.0266?R2*, with a constant coefficient-of-variation of 0.32. DATA CONCLUSION:
      FerriScan and R2* techniques were found to provide equivalent quantification of
      LIC in this study. Any difference in accuracy or precision was at a level lower
      than the uncertainty caused by variation in LIC over the liver. LEVEL OF
      EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 30291650
TI  - Anatomical location, sex, and age influence murine arterial circumferential
      cyclic strain before and during dobutamine infusion.
AB  - BACKGROUND: One of the primary biomechanical factors influencing arterial health
      is their deformation across the cardiac cycle, or cyclic strain, which is often
      associated with arterial stiffness. Deleterious changes in the cardiovascular
      system, e.g., increased arterial stiffness, can remain undetected until the
      system is challenged, such as under a cardiac stressor like dobutamine. PURPOSE:
      To quantify cyclic strain in mice at different locations along the arterial tree
      prior to and during dobutamine infusion, while evaluating the effects of sex and
      age. STUDY TYPE: Control/cohort study. ANIMAL MODEL: Twenty C57BL/6 mice; male,
      female; ~12 and 24 weeks of age; n = 5 per group. FIELD STRENGTH/SEQUENCE: 7T;
      CINE MRI with 12 frames, velocity compensation, and prospective cardiac gating.
      ASSESSMENT: Prior to and during the infusion of dobutamine, Green-Lagrange
      circumferential cyclic strain was calculated from perimeter measurements derived
      from CINE data acquired at the carotid artery, suprarenal and infrarenal
      abdominal aorta, and iliac artery. STATISTICAL TESTS: Analysis of variance
      (ANOVA) followed by post-hoc tests was used to evaluate the influence of
      dobutamine, anatomical location, sex, and age. RESULTS: Heart rates did not
      differ between groups prior to or during dobutamine infusion (P = 0.87 and P =
      0.08, respectively). Dobutamine increased cyclic strain in each group. Within a
      group, increases in strain were similar across arteries. At the suprarenal aorta,
      strain was reduced in older mice at baseline (young 27.6 > mature 19.3%, P =
      0.01) and during dobutamine infusion (young 53.0 > mature 36.2%, P = 0.005). In
      the infrarenal aorta, the response (dobutamine - baseline) was reduced in older
      mice (young 21.9 > mature 13.5%, P = 0.04). DATA CONCLUSION: Dobutamine infusion
      increases circumferential cyclic strain throughout the arterial tree of mice.
      This effect is quantifiable using CINE MRI. The results demonstrate that strain
      prior to and during dobutamine is influenced by anatomical location, sex, and
      age. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging
      2018.

PMID- 30291651
TI  - Increased iron deposition of deep cerebral gray matter structures in hemodialysis
      patients: A longitudinal study using quantitative susceptibility mapping.
AB  - BACKGROUND: The cerebral iron overload in hemodialysis patients has been reported
      in a previous study, in which the evaluation of the changes in iron content could
      be affected by the cross-sectional analysis. PURPOSE: To investigate the
      longitudinal changes of iron deposition in hemodialysis patients using
      quantitative susceptibility mapping (QSM) and correlate these findings with the
      longitudinal changes of neurocognitive function and clinical factors. STUDY TYPE:
      Prospective; longitudinal. POPULATION: In all, 34 patients and 30 healthy
      controls (HCs); the mean follow-up interval was 22 +/- 7 months. FIELD
      STRENGTH/SEQUENCE: 3.0T, susceptibility-weighted imaging (SWI). ASSESSMENT: QSM
      reconstructed from original phase data of SWI was used to measure the
      susceptibility of gray matter structures including bilateral caudate nucleus
      (CN), globus pallidus (GP), putmen (PUT), red nucleus (RN), substantia nigra
      (SN), dentate nucleus (DN), thalamus (THA), pulvinar of thalamus (PT). The Mini
      Mental State Examination (MMSE) test and clinical factors were recorded.
      STATISTICAL TESTING: Analysis of covariance adjusting for age and gender as
      covariates or a paired t-test for the differences in susceptibility, MMSE scores,
      and clinical factors among baseline, follow-up patients, and HCs. Correlation and
      stepwise regression analysis for the relationship between susceptibility, MMSE
      scores, and clinical factors. RESULTS: The susceptibility of bilateral CN, GP,
      PUT, RN, SN, DN, THA, PT in follow-up patients was significantly higher than that
      in baseline between patients and HCs except for left THA (all P < 0.05;
      Bonferroni corrected). MMSE scores significantly negatively correlated with the
      susceptibility of bilateral CN, PUT, and RRN in the baseline examination and
      bilateral CN, PUT, RN, and DN in the follow-up examination (all P < 0.05; false
      discovery rate [FDR] corrected). The follow-up interval, creatinine, phosphorus,
      and calcium were independent factors for the increased susceptibility of some
      nuclei (all P < 0.05). DATA CONCLUSION: The iron deposition of gray matter nuclei
      in hemodialysis patients increased over roughly a 2-year period and may be a risk
      factor for neurocognitive impairment. Creatinine and abnormal calcium-phosphorus
      metabolism were independent risk factors for abnormal iron deposition. LEVEL OF
      EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.

PMID- 30291652
TI  - Quantitative MRI of Visually Intact Rotator Cuff Muscles by Multiecho Dixon-Based
      Fat Quantification and Diffusion Tensor Imaging.
AB  - BACKGROUND: Quantitative MRI allows assessment of shoulder rotator cuff (RC)
      muscles by Dixon MR sequences with calculation of fractional fat content (FF%)
      maps and diffusion tensor imaging (DTI) including tractography. PURPOSE: To
      compare FF% and DTI derived parameters among visually intact RC muscles, to
      compare 2D with 3D DTI measurements and to establish normative values. STUDY
      TYPE: Prospective. SUBJECTS: Forty patients aged >18 years undergoing shoulder MR
      arthrography were included. FIELD STRENGTH/SEQUENCE: MR arthrography of the
      shoulder including 3D multiecho Dixon and 3D echo-planar DTI sequences (15
      gradient encoding directions, b-value 600 s/mm2 ) was performed at 3.0T.
      ASSESSMENT: Muscles affected by RC tears or fatty infiltration of Goutallier
      grade >=1 were excluded. Two independent radiologists measured FF%, apparent
      diffusion coefficient (ADC), and fractional anisotropy (FA) by region-of-interest
      (ROI) placements at the Y-position of the scapula and 3D tractography of each
      muscle with qualitative evaluation was performed. STATISTICAL TESTS: Intraclass
      correlation coefficients (ICCs) and Cohen's kappa were used for interreader
      agreement and Pearson correlation coefficient to correlate quantitative measures
      with each other and age, independent-samples t-test, one-way analysis of variance
      (ANOVA), and Kruskal-Wallis test were performed to investigate differences
      between genders and muscles. RESULTS: Qualitative and quantitative measurements
      showed moderate (kappa = 0.41-0.56) to almost perfect (ICC = 0.75-0.99)
      agreement. There were weak but significant positive correlations of FF% with age
      (r = 0.273, P < 0.05) and FA-2D (r = 0.319-0.383, P < 0.05). Significant
      differences were found among RC muscles for ADC, radial diffusivity (RD), and
      tract homogeneity (all P < 0.05) but not between genders (all P >= 0.05). High
      correlations of 2D with 3D measurements for ADC (r = 0.639, P < 0.001) and FA (r
      = 0.628, P < 0.001) were seen. DATA CONCLUSION: Quantitative MRI with estimation
      of FF% and DTI parameters shows significant age-associated changes and
      differences among visually intact RC muscles. High reproducibility and
      correlations of 2D with 3D DTI measurements can be expected. LEVEL OF EVIDENCE: 2
      Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 30291653
TI  - Evaluation of Focal Laser Ablation of Prostate Cancer Using High Spectral and
      Spatial Resolution Imaging: A Pilot Study.
AB  - BACKGROUND: Focal laser ablation (FLA) is a minimally invasive thermal ablation,
      guided by MRI through an optical fiber, to induce coagulative necrosis in cancer.
      PURPOSE: To evaluate the feasibility of high spectral and spatial resolution
      imaging using multiecho gradient echo (MEGE) MRI for identification of ablation
      zones, after FLA of prostate cancers. STUDY TYPE: Prospective. POPULATION:
      Fourteen patients with biopsy-confirmed localized prostate cancers. FIELD
      STRENGTH/SEQUENCE: FLA was performed under monitored conscious sedation with a
      1.5T MRI scanner. Axial MEGE images were acquired before and after the last FLA.
      Pre- and postcontrast enhanced T1 -weighted (pT1 W) images were acquired to
      assess the FLA zone as a reference standard. ASSESSMENT: The  STATISTICAL TESTS:
      Nonparametric Kruskal-Wallis tests were performed to determine whether there was
      significant difference in calculated ablation areas and volumes between  RESULTS:
      Average  LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging
      2018.

PMID- 30291654
TI  - Absolute Quantification of Phosphor-Containing Metabolites in the Liver Using 31
      P MRSI and Hepatic Lipid Volume Correction at 7T Suggests No Dependence on Body
      Mass Index or Age.
AB  - BACKGROUND: Hepatic disorders are often associated with changes in the
      concentration of phosphorus-31 (31 P) metabolites. Absolute quantification offers
      a way to assess those metabolites directly but introduces obstacles, especially
      at higher field strengths (B0 >= 7T). PURPOSE: To introduce a feasible method for
      in vivo absolute quantification of hepatic 31 P metabolites and assess its
      clinical value by probing differences related to volunteers' age and body mass
      index (BMI). STUDY TYPE: Prospective cohort. SUBJECTS/PHANTOMS: Four healthy
      volunteers included in the reproducibility study and 19 healthy subjects arranged
      into three subgroups according to BMI and age. Phantoms containing 31 P solution
      for correction and validation. FIELD STRENGTH/SEQUENCE: Phase-encoded 3D pulse
      acquire chemical shift imaging for 31 P and single-volume 1 H spectroscopy to
      assess the hepatocellular lipid content at 7T. ASSESSMENT: A phantom replacement
      method was used. Spectra located in the liver with sufficient signal-to-noise
      ratio and no contamination from muscle tissue, were used to calculate following
      metabolite concentrations: adenosine triphosphates (gamma- and alpha-ATP);
      glycerophosphocholine (GPC); glycerophosphoethanolamine (GPE); inorganic
      phosphate (Pi ); phosphocholine (PC); phosphoethanolamine (PE); uridine
      diphosphate-glucose (UDPG); nicotinamide adenine dinucleotide-phosphate (NADH);
      and phosphatidylcholine (PtdC). Correction for hepatic lipid volume fraction
      (HLVF) was performed. STATISTICAL TESTS: Differences assessed by analysis of
      variance with Bonferroni correction for multiple comparison and with a Student's
      t-test when appropriate. RESULTS: The concentrations for the young lean group
      corrected for HLVF were 2.56 +/- 0.10 mM for gamma-ATP (mean +/- standard
      deviation), alpha-ATP: 2.42 +/- 0.15 mM, GPC: 3.31 +/- 0.27 mM, GPE: 3.38 +/-
      0.87 mM, Pi : 1.42 +/- 0.20 mM, PC: 1.47 +/- 0.24 mM, PE: 1.61 +/- 0.20 mM, UDPG:
      0.74 +/- 0.17 mM, NADH: 1.21 +/- 0.38 mM, and PtdC: 0.43 +/- 0.10 mM. Differences
      found in ATP levels between lean and overweight volunteers vanished after HLVF
      correction. DATA CONCLUSION: Exploiting the excellent spectral resolution at 7T
      and using the phantom replacement method, we were able to quantify up to 10 31 P
      containing hepatic metabolites. The combination of 31 P magnetic resonance
      spectroscopy imaging data acquisition and HLVF correction was not able to show a
      possible dependence of 31 P metabolite concentrations on BMI or age, in the small
      healthy population used in this study. LEVEL OF EVIDENCE: 2 Technical Efficacy:
      Stage 1 J. Magn. Reson. Imaging 2018.

PMID- 30291655
TI  - Disrupted functional connectivity and activity in the white matter of the
      sensorimotor system in patients with pontine strokes.
AB  - BACKGROUND: White matter (WM) blood oxygenation level-dependent (BOLD) signals
      are reported to be related to neural activity. However, sensitivity of WM BOLD
      signals to disease remains unclear. PURPOSE: To investigate WM BOLD signal
      changes, directional variations of resting-state correlations in sensorimotor
      system in patients with pontine strokes, and to determine the relationship
      between WM BOLD signals and motor deficits. STUDY TYPE: Prospective. SUBJECTS:
      Ethical approval was obtained from the local Ethics Committee and each
      participant gave written informed consent. Sixteen patients with focal pontine
      lesions and 16 age-matched control subjects were included. FIELD
      STRENGTH/SEQUENCE: 3.0T T1 -weighted anatomic images using a 3D magnetization
      prepared rapid gradient-echo sequence. Resting-state fMRI images using gradient
      echo echo-planar imaging sequence. Diffusion-weighted images using single-shot
      spin-echo diffusion echo-planar imaging. ASSESSMENT: Relevant WM tracts in the
      sensorimotor system by region of interest-wise analysis were identified. Power
      spectra of BOLD signals and anisotropy of resting-state correlations were
      measured in sensorimotor system and compared between two groups. Their
      relationships with clinical scores were analyzed. STATISTICAL TESTS: Two-sample t
      test; partial correlation analysis. RESULTS: Power spectra of BOLD signals in
      nerve tracts on the ipsilesional side were significantly decreased (P < 0.05).
      Compared with that in healthy subjects, the anisotropy of resting-state
      correlations along identified WM tracts was decreased in the thalamus
      dorsolateral prefrontal cortex bundle on the contralesional side, and all nerve
      tracts on the ipsilesional side. Partial least squares regression analysis showed
      the predicted outcome scores correlated significantly with actual Fugl-Meyer
      scores (R2  = 0.944, P = 0.013). DATA CONCLUSION: Our findings suggest that
      disrupted activity and functional connectivity in WM areas of the sensorimotor
      system can be detected in pontine strokes, and may serve as a biomarker for motor
      function prediction. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn.
      Reson. Imaging 2018.

PMID- 30291656
TI  - PET/MRI in Breast Cancer.
AB  - : Positron emission tomography / magnetic resonance imaging (PET/MRI) is an
      emerging imaging technology that allows for the acquisition of multiple MRI
      parameters simultaneously with PET data. In this review, we address the technical
      requirements of PET/MRI including protocols and tracers, the potential of
      integrated localized breast PET/MRI exams, and possible applications of whole
      body PET/MRI in breast cancer patients. Currently, PET/MRI can be performed on
      sequential and integrated PET/MRI scanners but, as not all practices can access
      these dedicated machines, several studies look at PET and MRI exams that are
      performed separately on separate scanners within a short time frame. This
      practice likely provides similar clinical data, although exact colocalization for
      iso-voxel analysis, currently performed only in research, is not possible. In
      PET/MRI, the MRI sequences are flexible and can be customized according to the
      aim of the exam. The most commonly used radiotracer is 18 F-FDG; however, tracers
      that image hypoxia and drug targets such as estrogen receptors and HER2 are in
      development and may increase the utility of PET/MRI. For dedicated breast
      PET/MRI, a potential advantage over standard breast MRI alone may be the
      complementary sensitivities of MRI for extent of disease within the breast and
      PET for axillary and internal mammary nodal metastases. Moreover, layers of
      multiparametric MRI and PET metrics derived from the index lesion are being
      investigated as predictors of response to neoadjuvant therapy. These data may
      eventually be able to be quantified and mined in a way that furthers radiomics
      and also precision medicine. Finally, in whole-body imaging of breast cancer
      patients, single-institution studies have found that PET/MRI detects more
      metastases than PET at about half the radiation dose, although a survival benefit
      has not been shown. For now, whole-body PET/MRI in breast cancer patients may be
      most relevant for young patients who may undergo serial surveillance exams. LEVEL
      OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 30291657
TI  - A melanin-based trait is more strongly related to body size in the tropics than
      in temperate regions in the globally distributed barn owl family.
AB  - Life history traits differ between organisms living in the tropics, Northern and
      Southern Hemispheres, and sexual selection is thought to be stronger close to the
      equator than in temperate regions. Although birds are often supposed to be more
      brightly coloured in the tropics, the current evidence of geographic variation in
      the intensity of sexual selection and sex-specific natural selection is
      equivocal. Whether sex-specific traits signal aspects of individual quality
      better in the tropics than in the temperate regions of the Northern and Southern
      Hemispheres therefore remains an open question. We examined predictions of this
      hypothesis in the Tytonidae family (barn owls and their relatives) because
      females, on average, display larger black spots on the tip of their ventral body
      feathers than males, and this trait is associated with aspects of individual
      quality. We measured the size of melanic spots and the wing length of 7893
      Tytonidae skins collected worldwide and preserved in natural history museums. The
      covariation between spot size and wing length was stronger in females than in
      males, in large- than small-spotted Tyto taxa and close to the equator than in
      temperate regions. This suggests that selection for spot size, which can be used
      by owls as an additional cue to assess individual body size and other aspects of
      phenotypic quality, is stronger in females than in males, particularly near the
      equator.

PMID- 30291658
TI  - Long term social consequences of adolescent pregnancy.

PMID- 30291659
TI  - Surface-Enhanced Raman Spectroscopy for the Detection of a Metabolic Product in
      the Headspace Above Live Bacterial Cultures.
AB  - In situ surface-enhanced Raman spectra of the headspace above cultures of six
      bacterial species showed strong characteristic bands from chemisorbed methyl
      sulfide. This marker compound is created by dissociation of dimethyl disulfide
      (DMDS), a fermentative metabolite of bacteria, on the surface of the enhancing Au
      or Ag nanoparticle films. Kinetic binding plots of media spiked with DMDS and of
      live cultures showed that the Au-based substrates were more suitable for the
      rapid detection of bacteria than Ag-based substrates. For E. coli DH5alpha, the
      sensitivity limit for headspace SERS detection was 1.5*107  CFU mL-1 , which
      corresponded to detection 15 min after inoculation of the growth medium. Since
      the metabolites are only produced by viable bacteria, antibiotic (gentamicin)
      treatment stopped the normal signal growth of the marker peak. This work is a
      promising step towards rapid bedside detection of bacterial infections and rapid
      screening of antibiotics against bacteria.

PMID- 30291660
TI  - Synthesis, characterization, antioxidant, antidiabetic, anticholinergic, and
      antiepileptic properties of novel N-substituted tetrahydropyrimidines based on
      phenylthiourea.
AB  - In the presence of trifluoroacetic acid, on the basis of three-component
      condensation of phenylthiourea with its salicylaldehyde and methyl-3
      oxobutanoate, an efficient method for the synthesis of 1-(4-(2-hydroxyphenyl)-6
      methyl-1-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)ethanone (I) has been
      worked out. These novel N-substituted tetrahydropyrimidines based on
      phenylthiourea showed good inhibitory action against acetylcholinesterase (AChE),
      alpha-glycosidase, and human carbonic anhydrase (hCA) isoforms I and II. K i
      values of AChE enzyme were in the range of 0.48 to 7.46 nM. The hCA I and II were
      effectively inhibited by the compounds, with K i values in the range of 502.44 to
      923.11 nM for hCA I and 400.32 to 801.57 nM for hCA II, respectively. The
      antioxidant activity of the novel N-substituted tetrahydropyrimidines based on
      phenylthiourea was investigated by using different in vitro antioxidant assays;
      including 1,1-diphenyl-2-picrylhydrazyl (DPPH.) radical scavenging, Cu 2+  and Fe
      3+ reducing activities.

PMID- 30291661
TI  - Telomere length analysis in residents of a community exposed to arsenic.
AB  - Differentiated cells telomere length is an indicator of senescence or lifespan;
      however, in peripheral blood leukocytes the relative shortening of the telomere
      has been considered as a biological marker of aging, and lengthening telomere as
      an associated risk to cancer. Individual's age, type of tissue, lifestyle, and
      environmental factors make telomere length variable. The presence of
      environmental carcinogens such as arsenic (As) influence as causal agents of
      these alterations, the main modes of action for As described are oxidative
      stress, reduction in DNA repair capacity, overexpression of genes, alteration of
      telomerase activity, and damage to telomeres. The telomeres of leukocytes
      resulting a finite capacity of replication due to the low or no activity of the
      telomerase enzyme, therefore, elongation telomere in this kind of cells is a
      potential biological marker associated with the development of chronic diseases
      and carcinogenesis.

PMID- 30291662
TI  - Hailey-Hailey disease successfully treated with vitamin D oral supplementation.
AB  - Hailey-Hailey disease (HHD) also known as familial benign chronic pemphigus is a
      rare autosomal dominant genodermatosis. HHD treatment is often not satisfactory
      and hence, various modalities of treatment have been tried. We describe the case
      of a 37-year-old woman with a 2 years history of macerated erythematous plaques
      along with erosions, fissures, and crusts located on axillae and submammary
      areas, successfully treated with only oral supplementation of vitamin D (800
      I.U./die) for 3 months. We reported this case to suggest that oral vitamin D may
      be enumerated in the various treatments proposed for HHD so far due to its rapid
      efficacy on skin lesions and symptoms.

PMID- 30291664
TI  - Recent Advances in Alkyl Carbon-Carbon Bond Formation by Nickel/Photoredox Cross
      Coupling.
AB  - The union of photoredox and nickel catalysis has resulted in a renaissance in
      radical chemistry as well as in the use of nickel-catalyzed transformations,
      specifically for carbon-carbon bond formation. Collectively, these advances
      address the longstanding challenge of late-stage cross-coupling of functionalized
      alkyl fragments. Empowered by the notion that photocatalytically-generated alkyl
      radicals readily undergo capture by Ni complexes, wholly new feedstocks for cross
      coupling have been realized. Herein, we highlight recent developments in several
      types of alkyl cross-couplings that are accessible exclusively through this
      approach.

PMID- 30291665
TI  - Improving the effectiveness of lifestyle interventions for gestational diabetes
      mellitus prevention (what would Janus do?).

PMID- 30291663
TI  - Phytochemical screening and antityrosinase activity of carvacrol, thymoquinone,
      and four essential oils of Lebanese plants.
AB  - OBJECTIVE: In our study, we aim to explore the ability of four essential oils
      (EO) of Lebanese plants to inhibit the tyrosinase activity and to correlate their
      efficiency level to their phytochemical compositions. METHODS: The EO have been
      extracted by hydrodistillation using a Clevenger apparatus and have been studied
      by GC-MS analysis. Active compounds of Origanum species were identified and
      antityrosinase activities of EO and active molecules (carvacrol and thymoquinone)
      have been tested in tubo. RESULTS: Antityrosinase activities were obtained as
      follows: EO of Origanum syriacum (80.41% +/- 2.00%), EO of Origanum ehrenbergii
      (45.33% +/- 2.20%), EO of Salvia fruticosa (14.62% +/- 2.30%), EO of Calamintha
      origanifolia (16.51% +/- 5.80%), Carvacrol (56.55% +/- 3.10%), and Thymoquinone
      (19.49% +/- 1.50%). CONCLUSION: Origanum essential oils resulted in the highest
      antityrosinase activity due to their high content in carvacrol. However, when
      present together with carvacrol, thymoquinone decreases the efficiency of
      carvacrol, which is the case of O. ehrenbergii essential oil. Thus, for improved
      antityrosinase activity, O. syriacum and O. ehrenbergii should be harvested
      during flowering stage where carvacrol is present at its highest dosage and
      thymoquinone at its lowest.

PMID- 30291666
TI  - Enantioselective synthesis of enantiopure chiral alcohols using carbonyl
      reductases screened from Yarrowia lipolytica.
AB  - AIMS: We aimed to explore Yarrowia lipolytica carbonyl reductases as effective
      biocatalysts and to develop efficient asymmetric reduction systems for chiral
      alcohol synthesis. METHODS AND RESULTS: Yarrowia lipolytica carbonyl reductase
      genes were obtained via homologous sequence amplification strategy. Two carbonyl
      reductases, YaCRI and YaCRII, were identified and characterized, and used to
      catalyse the conversion of 2-hydroxyacetophenone (2-HAP) to optically pure (S)-1
      phenyl-1,2-ethanediol. Enzymatic assays revealed that YaCRI and YaCRII exhibited
      specific activities of 6.96 U mg-1 (99.8% e.e.) and 7.85 U mg-1 (99.9% e.e.),
      respectively, and showed moderate heat resistance at 40-50 degrees C and acid
      tolerance at pH 5.0-6.0. An efficient whole-cell two-phase system was established
      using reductase-expressing recombinant Escherichia coli. The conversion of 2-HAP
      (20.0 g l-1 ) conversion with the solvent of dibutyl phthalate was approximately
      70-fold higher than in water. Furthermore, the two recombinant E. coli displayed
      biocatalyst activity and enantioselectivity towards several different carbonyl
      compounds, and E. coli BL21 (DE3)/pET-28a-yacrII showed a broad substrate
      spectrum. CONCLUSIONS: A new whole-cell recombinant E. coli-based bioreduction
      system for enantiopure alcohol synthesis with high enantioselectivity at high
      substrate concentrations was developed. SIGNIFICANCE AND IMPACT OF THE STUDY: We
      proposed a promising approach for the efficient preparation of enantiopure chiral
      alcohols.

PMID- 30291667
TI  - Synthesis of BCP Benzylamines From 2-Azaallyl Anions and [1.1.1]Propellane.
AB  - For bioactive molecules, bicyclo[1.1.1]pentanes (BCPs) are an emerging isostere
      of rigid spacer groups that have shown potential to improve drug-like qualities.
      As BCPs become an increasingly popular motif for evaluation in drug candidates,
      organic chemists must meet the demand to reliably incorporate them into new
      targets. To provide access to BCP analogues of diaryl methanamines, a ubiquitous
      scaffold in medicinal chemistry, we report the synthesis of BCP benzylamines
      through reactivity of [1.1.1]propellane with 2-azaallyl anions, which are
      generated in situ from N-benzyl ketimines. The reaction proceeds rapidly at room
      temperature and tolerates a broad substrate scope, providing straightforward
      access to 23 new BCP benzylamine derivatives. Initial experiments support the
      intermediacy of a BCP anion. Additionally, the reaction can be promoted by
      substoichiometric loadings of base, highlighting an unusual reactivity of both 2
      azaallyls and [1.1.1]propellane.

PMID- 30291668
TI  - Tissue Regeneration Enhancer Elements: A Way to Unlock Endogenous Healing Power.
AB  - Regenerative capacity is widespread throughout almost all animal phyla. However,
      the distribution pattern remains incompletely understood. Various examples show
      that very closely related species display different regenerative capacities. Why
      and how have diverse regenerative capacities evolved across species? One
      prevailing thought in the field of regeneration is that most regeneration
      associated factors are evolutionarily conserved, suggesting the existence of an
      innate tissue regeneration ability in all species. However, its regulation is
      differentially controlled in distinct species, resulting in heterogeneous
      regenerative capabilities. In this review, we discuss regeneration-associated
      enhancers, the key cis-regulatory elements controlling gene expression, their
      underlying molecular mechanisms, and their influence on regenerative capacity.
      Understanding the regulatory mechanisms of regeneration enhancers can provide
      fundamental insights into tissue regeneration and further help us develop
      therapeutic strategies to unlock latent healing powers in humans. Developmental
      Dynamics 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30291669
TI  - Application of the MADS classification system in a "mega mammoth" stent trial:
      Feasibility and preliminary clinical implications.
AB  - OBJECTIVES AND BACKGROUND: We attempted to test the feasibility of application of
      the MADS classification system in the largest stent trial to date and evaluate
      the preliminary clinical implications of this approach. METHODS: In the
      randomized GLOBAL LEADERS trial, testing two different antiplatelet strategies in
      patients undergoing PCI with bivalirudin and biolimus-eluting stents, the e-CRF
      was dedicated to bifurcation treatment according to the MADS classification.
      Based on this e-CRF, the techniques used for bifurcations treatment in GLOBAL
      LEADERS were described and compared with two large, all-comer registries of
      bifurcations treatment (I-BIGIS and COBIS), used as historical controls. RESULTS:
      Among 15,991 patients enrolled in the trial, 22,921 lesions treated at the index
      and staged procedure were available for analysis and 2,757 of these lesions were
      bifurcations and 7 were trifurcation lesions. The e-CRF-based MADS classification
      was achieved in 2,757 of these lesions (100%). 80.3% of bifurcations were treated
      using a single stent, 18.9% using 2 stents and 0.7% using 3 stents. Overall, the
      "main across side first" approach (A) was used in 77.4% with the "side branch
      first" approach (S) being the second most frequently used technique (10.2%). A
      single stent was used in the majority of the "A" approach (87.9%). A reduction in
      the use of 2-stent techniques (from 33.9 to 18.9%) was observed between GLOBAL
      LEADERS and I-BIGIS. The "A" approach was the most frequently used technique in
      GLOBAL LEADERS, while in COBIS the "S" strategy was most frequently employed.
      CONCLUSIONS: Application of the MADS classification through an e-CRF was feasible
      in the largest stent trial today and provided useful information about the trends
      observed overtime in the treatment of bifurcation lesions.

PMID- 30291670
TI  - Use of a novel 589-nm solid-state laser for treatment of facial erythema.
AB  - OBJECTIVE: To evaluate the efficacy and safety associated with use of a 589-nm
      solid-state laser for treatment of facial erythema. METHODS: A prospective, IRB
      approved study was conducted. Participants who were interested in treatment for
      facial erythema were recruited. They received four monthly treatments with the
      589-nm laser. Erythema of the right and left face was graded on a scale of 0-4, 4
      being most severe, by both investigators and participants prior to each treatment
      and at follow-up. Safety was assessed by any reported side effects. RESULTS:
      Twenty-four participants enrolled in the study, 16 women (67%) and 8 men (33%),
      with an average age of 51.1 years. Investigator grades showed a statistically
      significant improvement in erythema of 31% for both the right and left face.
      Participant grades showed a statistically significant improvement in erythema of
      23.2% for the right face and 22.8% for the left face. Side effects were limited
      to transient erythema posttreatment. CONCLUSION: A 589-nm solid-state laser
      achieved a modest improvement in facial erythema when evaluating results 1 month
      after four monthly treatments. No major safety issues were reported.

PMID- 30291671
TI  - Highly Enantiospecific Borylation for Chiral alpha-Amino Tertiary Boronic Esters.
AB  - Herein we report a highly efficient and enantiospecific borylation method to
      synthesize a wide range of enantiopure (>99 % ee) alpha-amino tertiary boronic
      esters. The configurationally stable alpha-N-Boc substituted tertiary
      organolithium species and pinacolborane (HBpin) underwent enantiospecific
      borylation at -78  degrees C with the formation of a new stereogenic C-B bond.
      This reaction has a broad scope, enabling the synthesis of various alpha-amino
      tertiary boronic esters in excellent yields and, importantly, with universally
      excellent enantiospecificity (>99 % es) and complete retention of configuration.

PMID- 30291672
TI  - Sustained Virological Response Is Associated with a Decreased Risk of
      Posttransplant Diabetes Mellitus in Liver Transplant Recipients with Hepatitis C
      Related Liver Disease.
AB  - Posttransplant diabetes mellitus (PTDM), an increasingly recognized complication
      of solid organ transplantation, is associated with increased morbidity and
      mortality following liver transplantation (LT). Hepatitis C virus (HCV) infection
      is a consistent and modifiable risk factor for PTDM. Prior studies have
      demonstrated improvement in glucose metabolism following sustained virological
      response (SVR). However, the effect of SVR on the incidence of PTDM has not been
      previously investigated in a large cohort of LT recipients. We performed a single
      center retrospective cohort study of LT recipients with HCV from January 1, 2010
      to June 30, 2015 to compare the risk of sustained posttransplant diabetes
      mellitus (s-PTDM) prior to and following SVR. SVR was treated as a discrete time
      varying exposure. The s-PTDM was defined as de novo diabetes mellitus following
      LT of a >6-month duration. Univariate and multivariate Cox proportional hazards
      models were used to compare crude and adjusted time to s-PTDM prior to and
      following SVR. There were 256 eligible LT recipients analyzed. Median follow-up
      was 41.2 months. Overall, 31 (12.1%) and 178 (69.5%) patients achieved SVR prior
      to LT and following LT, respectively. During follow-up, 71 (27.7%) patients
      developed s-PTDM. The incidence of s-PTDM was greatest in the first year after
      LT. After adjustment for potential confounders, SVR was associated with a
      significantly reduced risk of s-PTDM (HR, 0.40; P = 0.048). In conclusion,
      eradication of HCV is independently associated with a reduced incidence of s
      PTDM. This benefit appears to be most influenced by pre-LT SVR and persists
      throughout the post-LT period. Given the association between PTDM and
      posttransplant morbidity and mortality, these data provide another motivator for
      pre-LT or early post-LT treatment of HCV.

PMID- 30291673
TI  - Impact of face proportions on face attractiveness.
AB  - BACKGROUND: Proportions of face components appear to play a role in facial
      attractiveness. AIMS: The aim of the study was to establish the best proportions
      of face components in relation to whole face shape for facial attractiveness.
      METHODS: Only one face component (eye, nose, or lips) of a model in a series of
      photographs was altered using a computer program. Alterations consisted of size
      reduction or augmentation by 5% or 10%. Each photograph depicted a particular
      face component altered to either 90%, 95%, 100%, 105%, or 110% of its original
      size. Collages of photographs were shown to 167 individuals (male and female) for
      a fixed period of 7 seconds. Their task was to indicate the most attractive
      photograph of a model in a presented collage. RESULTS: In total, 48.1% of
      individuals preferred enhanced eyes both in males and females. We found that the
      preferred mean eye size in women was statistically significantly higher than that
      in men. In total, 64.8% of respondents preferred reduced nose proportions in
      women (27.5% found a reduction to 90% of the original size more attractive while
      37.3% preferred a reduction to 95%). It was demonstrated that the preferred mean
      nose size was statistically significantly lower in females in comparison with
      males. Respondents expressed a greater preference for nose reduction in women in
      comparison with men. 38.4% of respondents (in regard to both male and female
      mouth) preferred reduced mouth. 40.7% of respondents preferred reduced mouth in
      the female model. CONCLUSIONS: Our work delivers statistically significant
      evidence that facial attractiveness increases together with the enlargement of
      the uncovered eye surface as well as the reduction in nose and lip size. Data
      were obtained using modern collective intelligence methods of validation. Written
      consent was obtained from all study participants.

PMID- 30291674
TI  - Luminescent Thermometry by a Y/Eu Binary Layered Rare-Earth Hydroxide (LRH) via
      In Situ Intercalation with Neutral Terbium(III) Complexes.
AB  - Temperature-sensitive luminescent materials have aroused great interest for
      practical applications in optical sensors. Layered rare-earth hydroxides (LRHs)
      possess rich interlayer chemistry and adjustable composition; thus, they are the
      promising candidates for designing functional materials, usually through an ion
      exchange process. Herein, the intercalation of neutral TbIII complex rather than
      ion exchange was successfully performed in situ into the gallery of Y/Eu binary
      LRHs by using a hydrothermal process. Interestingly, the swollen LRHs are
      chameleon luminophores, exhibiting color emissions from green to pink that were
      tunable through variations in temperature ranging from 77 to 450 K. Because of
      the highly sensitive and temperature-dependent emissions, novel optical
      temperature sensors for 1D and 2D thermal imaging were fabricated by employing
      the chameleon luminophores, which displayed luminescence capable of reversibly
      undergoing repeated thermocycles. The present work opens up new fields in layered
      inorganic materials.

PMID- 30291677
TI  - Marc Verstraete (1925-2018).

PMID- 30291675
TI  - Adenosine deaminase inhibition suppresses progression of 4T1 murine breast cancer
      by adenosine receptor-dependent mechanisms.
AB  - The activity of a cell-surface ecto-adenosine deaminase (eADA) is markedly
      increased in the endothelial activation and vascular inflammation leading to
      decreased adenosine concentration and alterations in adenosine signalling.
      Depending on the specific pathway activated, extracellular purines mediate host
      cell response or regulate growth and cytotoxicity on tumour cells. The aim of
      this study was to test the effects of adenosine deaminase inhibition by
      2'deoxycoformycin (dCF) on the breast cancer development. dCF treatment decreased
      a tumour growth and a final tumour mass in female BALB/c mice injected
      orthotopically with 4T1 cancer cells. dCF also counteracted cancer-induced
      endothelial dysfunction in orthotopic and intravenous 4T1 mouse breast cancer
      models. In turn, this low dCF dose had a minor effect on immune stimulation
      exerted by 4T1 cell implantation. In vitro studies revealed that dCF suppressed
      migration and invasion of 4T1 cells via A2a and A3 adenosine receptor activation
      as well as 4T1 cell adhesion and transmigration through the endothelial cell
      layer via A2a receptor stimulation. Similar effects of dCF were observed in human
      breast cancer cells. Moreover, dCF improved a barrier function of endothelial
      cells decreasing its permeability. This study highlights beneficial effects of
      adenosine deaminase inhibition on breast cancer development. The inhibition of
      adenosine deaminase activity by dCF reduced tumour size that was closely related
      to the decreased aggressiveness of tumour cells by adenosine receptor-dependent
      mechanisms and endothelial protection.

PMID- 30291676
TI  - Dual functions of ARP101 in targeting membrane type-1 matrix metalloproteinase:
      Impact on U87 glioblastoma cell invasion and autophagy signaling.
AB  - Membrane type-1 matrix metalloproteinase (MT1-MMP) possesses both extracellular
      proteolytic and intracellular signal-transducing functions in tumorigenesis. An
      imbalance in MT1-MMP expression and/or function triggers a metastatic, invasive,
      and therapy resistance phenotype. MT1-MMP is involved in extracellular matrix
      (ECM) proteolysis, activation of latent MMPs, as well as in autophagy signaling
      in human hepatoma and glioblastoma cells. A low autophagy index in tumorigenesis
      has been inferred by recent studies where autophagic capacity was decreased
      during tumor progression. Here, we establish ARP101 as a dual-function small
      molecule inhibitor against MT1-MMP ECM hydrolysis and autophagy signal
      transducing functions in a model of grade IV glioblastoma cells. ARP101 inhibited
      concanavalin-A-mediated proMMP-2 activation into MMP-2, as well as MT1-MMP auto
      proteolytic processing. When overexpressing recombinant Wt MT1-MMP, ARP101
      inhibited proMMP-2 activation and triggered the formation of MT1-MMP oligomers
      that required trafficking to the plasma membrane. ARP101 further induced cell
      autophagy as reflected by increased formation of acidic vacuole organelles, LC3
      puncta, and autophagy-related protein ATG9 transcription. These were all
      significantly reversed upon siRNA-mediated gene silencing of MT1-MMP. ARP101 can
      thus concomitantly inhibit MT1-MMP extracellular catalytic function and exploit
      its intracellular transducing signal function to trigger autophagy-mediated cell
      death in U87 glioblastoma cancer cells.

PMID- 30291678
TI  - Gender and age differences in outcomes of patients with acute coronary syndromes
      referred for coronary angiography.
AB  - OBJECTIVES: The number of elderly patients undergoing coronary revascularization
      is steadily increasing, and data on the impact of gender on outcomes are scarce.
      This study sought to assess gender-related differences in outcomes in elderly
      patients with acute coronary syndromes (ACS). METHODS: We investigated outcomes
      in elderly ACS patients referred for coronary angiography and prospectively
      enrolled in the Swiss ACS Cohort between December 2009 and October 2012.
      Adjudicated major adverse cardiovascular and cerebrovascular events (MACCE)
      included all-cause death, non-fatal myocardial infarction, clinically indicated
      repeat coronary revascularization, definite stent thrombosis, and transient
      ischemic attack/stroke. RESULTS: Among 2,168 patients recruited, 481 (22%)
      patients were >75 years of age (37% women). In patients >75 years, 1-year MACCE
      rates were 15% and 23% in women and men (OR 0.59, 95% CI 0.36-0.97, P = 0.04),
      respectively, and differences remained significant after adjustments for baseline
      variables (adjusted OR 0.48, 95% CI 0.26-0.90, P = 0.02). Women >75 years had a
      lower cardiovascular mortality (6% versus 12%, adjusted OR 0.31, 95% CI 0.12
      0.81, P = 0.02). In patients <=75 years, 1-year MACCE rates did not differ
      between gender (10% and 8% for women and men, adjusted OR 1.28, 95% CI 0.77-2.14,
      P = 0.34). Rates of TIMI major bleeding for women and men were 4% and 4% in
      patients >75 years (P = 0.96), and 5% and 3% in those <=75 years (P = 0.11).
      CONCLUSIONS: The low rates of MACCE observed in elderly women in this patient
      cohort suggest that with current interventional strategies the gender gap in ACS
      management has been attenuated.

PMID- 30291679
TI  - Acceleration of Enzymatic Degradation of Poly(ethylene terephthalate) by Surface
      Coating with Anionic Surfactants.
AB  - Enzymatic degradation of poly(ethylene terephthalate) (PET) is promising because
      this process is safer than conventional industrial approaches. Recently, a
      cationic PET hydrolase (PETase) was identified from Ideonella sakaiensis. Pre
      incubation of a low-crystallinity PET film with anionic surfactants prior to
      initiating the reaction was found to improve PETase activity 120-fold. After 36 h
      at 30  degrees C, the film thickness decreased by 22 %. The binding of
      surfactants to the film makes the surface anionic, thereby attracting the
      cationic PETase. Mutagenesis of PETase showed that the surface cationic region
      formed by R53, R90, and K95, which are located on the same side as the substrate
      binding pocket, was crucial for efficient acceleration of activity by the anionic
      surfactant. Thus, surfactant bound on PET aligns the orientation of the active
      site to the surface, resulting in efficient hydrolysis. We believe that this
      approach using PETase could be further improved by designing surfactant molecules
      for the more efficient enzymatic PET degradation.

PMID- 30291680
TI  - A Systematic Evaluation of Effect of Adherence Patterns on the Sample Size and
      Power of a Clinical Study.
AB  - The objective of our study was to evaluate the effect of adherence patterns on
      the sample size and power of a clinical trial. Simulations from a population
      pharmacokinetic/pharmacodynamic (PK/PD) model linked to an adherence model were
      used. Four types of drug characteristics, such as long (~35 hours) and short (~12
      hours) half-life in combination with earlier or delayed time to reach steady
      state PD end points were studied. Adherence patterns were simulated using Markov
      chains. Our results clearly demonstrate the significant impact of varying levels
      and patterns of nonadherence on the sample size and power of a study. For drugs
      with short half-lives the evidence to support efficacy could be diluted by
      various patterns of nonadherence that would make its efficacy indistinguishable
      from the response to placebo. Prospectively utilizing clinical trial simulations
      with thorough incorporation of various adherence patterns would provide valuable
      information when designing a trial.

PMID- 30291681
TI  - Vertebral Comparative Anatomy and Morphological Differences in Anguine Lizards
      With a Special Reference to Pseudopus apodus.
AB  - The article reports on the first detailed vertebral and rib morphology of anguine
      taxon Pseudopus apodus using micro-computed tomography. A comparison shows
      significant morphological differences of vertebrae of Pseudopus relative to those
      of Anguis and Ophisaurus. Usually, there are 55 presacral vertebrae, two sacral,
      and 95-97 caudal vertebrae. Pseudopus apodus can be defined by 23 diagnostic
      features concerning the vertebral column. Although zygapophyseal articulation
      between atlas and axis is well developed in limbed anguid gerrhonotine lizards
      like Abronia or Barisia, it is absent in the extant representatives of the clade
      Anguinae, which are limbless. Thus, our study brings further support to the
      hypothesis about the complete reduction of this articulation in forms with
      reduced or absent limbs. Comparison of adult and juvenile morphology of vertebrae
      of P. apodus was also analyzed. Heterochrony in the evolution of this taxon was
      previously confirmed by its skull morphology and it can be also documented on the
      basis of vertebrae. Our data suggest that a peramorphic heterochronic process
      played a role in the evolution of this largest extant anguine species. Geometric
      morphometric analyses revealed a pattern of high vertebral disparity among
      species. We found a clear separation of limbless forms in morphospace. Pseudopus
      apodus always clusters within Ophisaurus-species confirming molecular and some
      morphological phylogenies. Only the first tail vertebra shows a distinct
      difference to those of other anguids, which might be related to altered
      locomotion associated to the larger body size in this species. Anat Rec, 2018.
      (c) 2018 Wiley Periodicals, Inc.

PMID- 30291682
TI  - Clinical evaluation of the lightening effect of cytidine on hyperpigmented skin.
AB  - BACKGROUND: Melanocytes, which reside in the basal layer of the epidermis,
      produce the pigment melanin in cytoplasmic organelles known as melanosomes.
      Melanosomes are transferred to keratinocytes which provide the color in our skin.
      Recently, Diwakar et  al reported the crucial roles of protein glycosylation in
      both melanogenesis and melanosome transfer to keratinocytes, and each was
      inhibited by the nucleotide cytidine. OBJECTIVE: The main objective of this study
      was to determine the clinical effects of topical application of cytidine to the
      hyperpigmented regions of the face in a group of human volunteers. METHODS: A
      randomized, vehicle-controlled study was conducted for 12 weeks on healthy Korean
      female subjects. Cytidine was formulated into the lotion at concentrations of 2%,
      3%, and 4% (w/w) and compared to the vehicle control formulation. The clinical
      outcomes were evaluated by performing visual assessment grading, measuring
      melanin index, skin brightness, and skin color parameters. In vitro skin
      penetration studies were conducted using Franz cell chambers for the 2% cytidine
      test formulation. RESULTS: The test group showed significant improvements in the
      visual assessment scores, melanin index, skin brightness, and skin color compared
      to the control group. Although significant dose-dependent improvements were seen
      in the clinical study, the in vitro Franz cell studies indicated that the
      clinical efficacy and potency of cytidine might be further enhanced by
      formulating a better topical delivery system, which will be the goal of our
      future studies. CONCLUSIONS: This randomized, double-blind, 12-week clinical
      study successfully demonstrated the efficacy of cytidine on skin depigmentation
      in a dose-dependent manner.

PMID- 30291683
TI  - The health consequences of falsified medicines- A study of the published
      literature.
AB  - OBJECTIVES: To analyse and present the literature describing the health
      consequences of falsified medicines, focusing on mortality and morbidity, as well
      as the scale of the issue, the geographic extent, the medicines affected, and the
      harm caused at both the individual and population levels. METHODS: We searched
      for articles in PubMed, using pre-optimized keywords '(counterfeit OR fake OR
      bogus OR falsified OR spurious) AND (medicine OR drug)'. Searches up to February
      2017 yielded 2006 hits, of which 1791 were full-length articles in English. Among
      them, we found 81 papers that qualitatively or quantitatively described 48
      incidents in which falsified medicines caused patients to suffer serious adverse
      effects, injury, symptoms or death. RESULTS: The distribution of incidents was
      examined according to the economic status of the countries involved, regional
      location in the world, therapeutic category of the medicines, number of incidents
      and victims by year, and characteristics of the falsified medicines. Among the 48
      reported incidents, 27 (56.3%) occurred in developing countries and 21 (43.7%) in
      developed countries. These incidents involved a total of approximately 7200
      casualties including 3604 deaths. CONCLUSIONS: Despite the poor quality of much
      of the reported data, the results of this study indicate that all types of
      medications have been targeted for falsification, and falsified medicines have
      had a serious impact on the health of both adults and children worldwide, with
      similar numbers of incidents in developing and developed countries.

PMID- 30291684
TI  - Possible Mechanisms for The Effects of Calcium Deficiency on Male Infertility.
AB  - Calcium (Ca) is a significant element that acts as an intracellular second
      messenger. It is necessary for many physiological processes in spermatozoa
      including spermatogenesis, sperm motility, capacitation, acrosome reaction and
      fertilization. Although influences of Ca deficiency on sperm function and male
      infertility have been widely studied, mechanisms for these abnormalities are not
      well considered. Poor sperm motility, impairment of chemotaxis, capacitation,
      acrosome reaction and steroidogenesis are the major mechanisms by which Ca
      deficiency induces male infertility. Therefore, an optimal seminal Ca
      concentration is required to strengthen sperm function and all steps leading to
      successful fertilization. Furthermore, identification of these mechanisms
      provides valuable information regarding the mechanisms of Ca deficiency on male
      reproductive system and the way for developing a better clinical approach. In
      this review, we aim to discuss the proposed cellular and molecular mechanisms of
      Ca deficiency on male reproductive system, sperm function and male fertility.
      Also we will discuss the valuable information currently available for the roles
      of Ca in male reproduction.

PMID- 30291685
TI  - An Overview of The Globozoospermia as A Multigenic Identified Syndrome.
AB  - Acrosome plays an integral role during fertilization and its absence in
      individuals with globozoospermia leads to failure of in vitro fertilization (IVF)
      and oocyte activation post-intracytoplasmic sperm injection (ICSI). A variety of
      processes, organelles and structures are involved in acrosome biogenesis
      including, trans-golgi network (TGN), acroplaxome and cellular trafficking. This
      review aims to explain roles of related signals and molecules involved in this
      process and also describe how their absence in form of mutation, deletion and
      knockout model may lead to phenomenon referred to globozoospermia.

PMID- 30291686
TI  - Prevalence of Sexual Dysfunction among Infertile Women in Iran: A Systematic
      Review and Meta-analysis.
AB  - Infertile women are at a higher risk of sexual dysfunction compared to fertile
      women. Infertility is a major source of stress, anxiety, and depression, which
      strongly affects sexual health. The aim of this study is to estimate the
      prevalence of female sexual dysfunction (FSD) among infertile Iranian women. We
      searched the main international databases (Web of Science, PubMed, Medline, and
      Scopus) and national databases (Scientific Information Database, Magiran, and
      IranMedex) from their inception until April, 2017. Due to heterogeneity between
      the studies, the extracted data were pooled using a random-effects model by Stata
      software. Out of 313 retrieved studies, we included 18 studies of 3419 infertile
      women in the meta-analysis. The pooled prevalence of FSD was 64.3% [95%
      confidence interval (CI): 53.3-75.3]. Our findings revealed that sexual desire
      (59.9%, 95% CI: 38.7-81.2) was the most prevalent disorder and vaginismus (19.2%,
      95% CI: 11.3-27.2) was the least prevalent among infertile women. The results of
      our metaanalysis suggested that more than 64% of infertile Iranian women reported
      sexual dysfunction, which was meaningfully high. This study also showed that
      sexual desire was significantly more common than other sexual dysfunction
      dimensions and the prevalence of vaginismus was the least common.

PMID- 30291687
TI  - Association of Tumor Necrosis Factor-alpha (TNF-alpha) -308G>A and -238G>A
      Polymorphisms with Recurrent Pregnancy Loss Risk: A Meta-Analysis.
AB  - Background: Multiple studies have been carried out examining the association of
      tumor necrosis factor-alpha gene (TNF-alpha) promoter region polymorphisms with
      recurrent pregnancy loss (RPL) risk. However, the results remain controversial
      and incomplete. Hence, we performed a meta-analysis to evaluate the association
      of the TNF-alpha -308G>A and -238G>A polymorphisms with RPL risk. Materials and
      Methods: In this meta-analysis, a comprehensive search of PubMed, Web of
      Knowledge and EMBASE was performed to identify relevant studies published until
      December 1, 2017. The associations were assessed by odds ratio (OR) and its
      corresponding 95% confidence interval (CI). Results: A total of 29 case-control
      studies, comprising 20 studies on TNF-alpha -308G>A (3,461 cases and 3,895
      controls) and nine studies on TNF-alpha -238G>A (2,589 cases and 2,664 controls),
      were included in the meta-analysis. Overall, we found TNF-alpha -308G>A to be
      associated with an increase in RPL risk under the homozygote (OR=1.716, 95% CI:
      1.210-2.433, P=0.002) and the recessive (OR=1.554, 95% CI: 1.100-2.196, P=0.012)
      models. TNF-alpha -238G>A was also significantly associated with increased risk
      of RPL under the allele model (OR=1.554, 95% CI: 1.100-2.196, P=0.012).
      Stratified analysis revealed a more significant association between theTNF-alpha 
      308G>A polymorphism and increased RPL risk in Asians under the homozygote
      (OR=2.190, 95% CI: 1.465-3.274, P<=0.001), the dominant (OR=1.642, 95% CI: 1.269
      2.125, P<=0.001) and the recessive (OR=1.456, 95% CI: 1.039-2.040, P=0.029)
      models, but not in Caucasians. A non-significant association was, however,
      identified between TNF-alpha -238G>A and RPL risk based on ethnicity. Moreover,
      TNF-alpha -308G>A and -238G>A polymorphisms were significantly associated with
      increased risk of RPL in high quality studies and polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) subgroups. Conclusion: The
      present meta-analysis demonstrates that TNF-alpha -308G>A and -238G>A
      polymorphisms are associated with an increased risk of RPL.

PMID- 30291688
TI  - Evaluation of Osteopontin Gene Expression in Endometrium of Diabetic Rat Models
      Treated with Metformin and Pioglitazone.
AB  - Background: Osteopontin (Opn) is one of the co-factors involved in cell adhesion
      and invasion during the implantation process. Several reports have shown Opn
      expression changes in diabetic condition in several tissues. In addition, an
      increased incidence of spontaneous abortion is reported in diabetic women. We,
      therefore, designed a study to evaluate the effects of diabetes on Opn expression
      at implantation time after treatment with metformin and pioglitazone. Materials
      and Methods: In this interventional and experimental study, 28 rats were randomly
      divided into four groups, namely control, diabetic, pioglitazone-treated diabetic
      rats and metformin-treated diabetic rats. Streptozotocin (STZ) and nicotinamide
      (NA) were used to induce type 2 diabetes (T2D). During the implantation window,
      the endometrium was removed and the expression of Opn was analysed by reverse
      transcription quantitative polymerase chain reaction (RT-qPCR). Results: Opn
      expression was significantly higher (30.70 fold-changes) in the diabetic group in
      comparison with the control group (P=0.04). Furthermore, the expression of Opn
      was significantly lower in the diabetic group treated with pioglitazone when
      compared with the diabetic group (P=0.04). Conclusion: According to the high Opn
      expression and the possibility of increased adhesion of endometrial epithelial
      cells, the invasion of blastocyst may be affected and thus reduced. As
      pioglitazone significantly reversed the upregulation of Opn in diabetic rats, it
      may be considered as a therapeutic compound for treating T2D.

PMID- 30291689
TI  - Detection of Partial AZFc Microdeletions in Azoospermic Infertile Men Is Not
      Informative of MicroTESE Outcome.
AB  - Background: Microdeletions of the Yq chromosome are among the most frequent
      genetic etiological factor of male infertility which spans the azoospermia factor
      regions (AZFa, AZFb and AZFc). Microdeletions are mostly seen in the AZFc region
      and usually cover genes actively involved in spermatogenesis. Partial AZFc
      microdeletions may also occur with various spans, namely gr/gr, b2/b3 and b1/b3.
      It is known that the outcome of microtesticular sperm extraction (TESE), the
      surgical process for sperm retrieval from the testis in infertile azoospermic
      men, may be predicted based on the type of AZF microdeletion. We therefore aimed
      to evaluate the correlation between partial AZFc microdeletions and microTESE
      results. Materials and Methods: In this cross-sectional study, 200 infertile
      azoospermic men referred to the Royan Institute were examined for the presence of
      partial AZFc microdeletions before undergoing microTESE. Partial AZFc
      microdeletions were detected by multiplex polymerase chain reaction (PCR) of
      seven different sequence-tagged site (STS) markers. The data were analyzed with
      the Chi-square test. Results: Among the 90 patients (45%) with a positive
      microTESE outcome, 9 (10%) showed a partial microdeletion in AZFc region. Of the
      110 (55%) patients with a negative microTESE outcome, 7 (6.3%) had an AZFc
      partial microdeletion. With respect to the span of the microdeletions, among the
      200 patients, 11 (5.5%) were gr/gr and 5 (2.5%) were b2/b3. Statistical analysis
      showed no significant difference between the patients with and without partial
      AZFc microdeletions with respect to microTESE outcome. Conclusion: Partial AZFc
      microdeletions is not a predictor of microTESE outcome in azoospermic men.

PMID- 30291690
TI  - Varicocelectomy May Improve Results for Sperm Retrieval and Pregnancy Rate in Non
      Obstructive Azoospermic Men.
AB  - Background: Assessing the net-results of microsurgical varicocelectomy in
      infertile men with non-obstructive azoospermic (NOA) and clinical varicocele in
      five years at Royan Institute. Materials and Methods: This is a descriptive
      retrospective cohort study. A backward-looking review of patients treated for NOA
      and varicocele from march 2011 to march 2016 was performed. In addition, MDTESE
      results of 57 patients with NOA and clinical varicocele, with 537 NOA patients
      without varicocele were compared. Results: Of 57 patients who underwent
      varicocelectomy, eight patients (14%) had sperm on sperm analysis post
      operatively. One of the eight patients was single, and one of them had
      spontaneous pregnancy (1/7) 14%, and one had a child by microinjection (1/7) 14%.
      Out of these 8 patients, 6 had hypospermatogenesis pathology. Of 38 patients who
      underwent MDTESE, 14 patients (36%) had sperm on their testis tissues, but one of
      them had no egg fertilization. Therefore, the fertilization rate was (92%). Of
      the remaining 13 patients, 3 had live child birth (3/13) 23%. Sperm retrieval
      rate (SRR) in NOA men without clinical varicocele was lower from those who had
      varicocele and NOA (22 vs. 36%). Also live birth rate in NOA men with
      varicocelectomy was higher than NOA men without varicocele (23 vs. 11%).
      Conclusion: Microsurgical varicocelectomy in NOA men may have positive effects on
      post-operative sperm in ejaculate and natural or assisted pregnancies, but it
      seems that the effect is more significant on MDTESE results and following
      successful microinjection. Meanwhile, SRR and live birth rate was higher in our
      patients compare to NOA men without clinical varicocele.

PMID- 30291691
TI  - Significant Correlation between High-Risk HPV DNA in Semen and Impairment of
      Sperm Quality in Infertile Men.
AB  - Background: Human papillomavirus (HPV) is a DNA virus that causes sexually
      transmitted infections (STI). Recent reports suggest that HPV may affect sperm
      parameters and lead to male infertility. This study aims to evaluate the
      correlation between seminal high-risk HPV infection and impairment of sperm
      quality in infertile Iranian men. Materials and Methods: In this case-control
      study, we collected fresh semen samples from 70 fertile men and 70 confirmed
      infertile men who referred to Yazd Infertility Centre in 2015. Semen analyses
      were performed according to the World Health Organization (WHO) guidelines. High
      risk HPV DNA was detected by real-time polymerase chain reaction (PCR). Results:
      A total of 140 subjects participated in the current study. Among 70 confirmed
      infertile males, only 8 (11.43%) cases tested positive for high-risk HPV and all
      fertile men were HPV-negative. This data revealed a significant association
      between high-risk HPV and male infertility (P=0.03). The percentage of normal
      sperm morphology and sperm motility rate significantly declined in men infected
      with HPV (P<0.001). Conclusion: There was a significantly higher prevalence of
      high-risk HPV in infertile men than fertile men. HPV infection seemed to be a
      risk factor for male infertility. Additional, larger studies should be conducted
      to confirm the impact of HPV on male infertility.

PMID- 30291692
TI  - Association between The Number of Retrieved Mature Oocytes and Insulin Resistance
      or Sensitivity in Infertile Women with Polycystic Ovary Syndrome.
AB  - Background: The objective of this study was to describe the association between
      luteinizing hormone (LH)/ follicle-stimulating hormone (FSH) ratio and
      demographic variables and maturation stage of oocytes in insulinresistant and
      insulin-sensitive patients with polycystic ovary syndrome (PCOS) in comparison
      with control group. Materials and Methods: In this case-control study, 60
      patients with in vitro fertilization (IVF)/intracytoplasmic sperm injection
      (ICSI) indication were subdivided into 3 groups as follow: 20 subjects were
      assigned to control (fertile women with male infertility history) group, 20
      subjects with PCOS were insulin resistant (IR) and 20 subjects with PCOS were
      insulin sensitive (IS). After puncture, retrieved oocytes were classified into
      metaphase II (MII) as mature and in metaphase I (MI) or germinal vesicle stage
      (GV) as immature. Regression analyses were used to explore the association
      between MII oocyte number and demographic and clinical variables. Results: LH/FSH
      ratio was significantly higher in PCOS-IR women compared to controls but not
      significantly different from that of PCOS-IS group. PCOS-IR women had lower MII
      oocyte number compared with that of controls. According to multiple regression
      analysis, the number of previous assisted reproductive technology (ART) cycles
      was negatively associated with the number of MII oocytes. Conclusion: Insulin
      resistance can be associated with reductions in MII oocyte number in patients
      with PCOS.

PMID- 30291693
TI  - Dietary Patterns and The Outcomes of Assisted Reproductive Techniques in Women
      with Primary Infertility: A Prospective Cohort Study.
AB  - Background: Infertility is one of the most common challenges that women in
      reproductive age would encounter today. The maternal nutritional status could be
      a determinant of oocyte quality and embryonic growth. This study was conducted to
      assess the relationship between dietary patterns and reproductive outcomes in
      infertile women. Materials and Methods: This prospective cohort study was
      conducted on 140 women with primary infertility who had referred to Isfahan
      Fertility and Infertility center, Isfahan, Iran. The average number of total
      oocytes and metaphase II oocytes, the fertilization rate, the ratio of good and
      bad quality embryo and biochemical and clinical pregnancy were considered as the
      outcomes of assisted reproductive techniques (ART). A 168-item food frequency
      questionnaire was used for estimating the dietary intakes during the last year.
      Factor analysis was used for identifying the dietary patterns and analysis of
      variance (ANOVA), analysis of covariance (ANCOVA), chi-square, and logistic
      regression analysis were used for assessing the relation between dietary patterns
      and ART's outcomes. Results: Three major dietary patterns (the healthy, western
      and unhealthy diet) were identified. Women with high adherence to the "healthy
      diet" had a higher educational level and were employed. There was a significant
      increase in the average number of total oocytes (P-trend=0.009) and metaphase II
      oocytes (P-trend=0.006) in the third tertile of "healthy diet" compared to the
      first tertile. Also, women with high adherence to the second tertile of
      "unhealthy" diet compared to the first tertile, had a significantly lower chance
      of getting pregnant [odds ratio (OR): 0.14, 95% confidence interval (CI): 0.3
      0.7]. Conclusion: Nutrition status could affect infertility treatment outcomes.
      Greater adherence to the healthy diet may enhance oocyte quality and quantity.
      Unhealthy diet could adversely affect the chance of getting pregnant.

PMID- 30291694
TI  - Satisfaction with Information Provided to Infertile patient Who Undergo Assisted
      Reproductive Treatment.
AB  - Background: Potentially modifiable factors, such as the appropriate informing
      process given to infertile patients, can affect their infertility knowledge and
      information. This study aims to assess infertility information provided to
      Iranians who undergo assisted reproductive treatment. Materials and Methods: In
      this cross-sectional study, participants recruited were a convenience sample of
      all infertile patients who received assisted reproductive treatments from Royan
      Institute, Tehran, Iran. Inclusion criteria consisted of: patient's first time
      visit, no previous infertility treatment failures, and referral to the centre
      between January and March 2015. A 20-item tool designed by researchers measured
      patient satisfaction with the infertility informing process. This tool included
      cause of infertility, type of recommended treatment, diagnostic procedures,
      approximate treatment duration, success rate of the treatment, approximate cost
      of treatment, and non-therapeutic factors in treatment success. Results: A total
      of 235 infertile patients were invited to participate in the study, from which
      200 (100 men and 100 women) participants completely responded to the
      questionnaire with a response rate of approximately 85%. The mean age of
      participants was 30.93 +/- 5.56 years. In terms of satisfaction with information
      provided about the cause of infertility, male responders reported the lowest mean
      score of 3.59 +/- 1.05 compared to female responders (3.82 +/- 0.85, P=0.078).
      Infertile women had a greater mean score of 3.85 +/- 0.78 than infertile men
      (3.58 +/- 1.29) in satisfaction with information provided about the type of
      recommended treatment (P=0.037). There was a statistically significant difference
      between males (3.26 +/- 1.04) and females (3.58 +/- 0.93) in satisfaction with
      approximate treatment duration (P=0.031). Conclusion: According to the results,
      most infertile patients were satisfied with the informing process related to the
      cause of infertility and recommended therapies. Information about infertility
      should be provided more systematically to all treated patients by medical staff,
      especially in terms of success rate of treatment and financial cost of therapy.

PMID- 30291695
TI  - Correlation of Maternal Stress Because of Positive Aneuploidy Screening Serum
      Analytes and Uterine Arteries' Doppler Ultrasound Index: A Prospective Cohort
      Study.
AB  - Background: Antenatal anxiety or maternal stress is a prevalent chronic mental
      disorder in pregnant women. We have assessed the effect of maternal stress from
      positive aneuploidy screening results on the changes in uterine artery blood
      flow. Materials and Methods: We performed a prospective cohort (one sample) pilot
      study at a hospital in Tehran, Iran. A total of 60 pregnant women who were
      candidates for amniocentesis due to abnormal sequential screening test results
      entered the study. We conducted 2 standard psychological tests, the Spielberger's
      State-Trait Anxiety Inventory and the Beck Anxiety Inventory, to determine
      anxiety levels in the participants before amniocentesis and two weeks after
      amniocentesis. The uterine artery resistance index was also measured before and
      two weeks after amniocentesis. The level of maternal stress was compared with the
      uterine artery resistance index. Results: Patients had a mean State Trait Anxiety
      Inventory score before amniocentesis of greater than 40, which meant that the
      mothers experienced high anxiety. There were no correlations between both
      inventories' anxiety scores and uterine artery blood flow before amniocentesis.
      However, two weeks after amniocentesis, we observed significant negative
      correlations between the State Anxiety (P=0.0041) and Trait Anxiety (P=0.010)
      Inventory scores and the uterine artery resistance indexes. Also, there was an
      association between the decreased right uterine artery resistance index and State
      Anxiety scores (P=0.036). There were significant correlations between State and
      Trait Anxiety scores and second trimester analytes of beta-human chorionic
      gonadotropin (beta-hCG, P<0.001), alpha-fetoprotein (P<0.001), and unconjugated
      estriol (P=0.048). Conclusion: Maternal anxiety because of positive aneuploidy
      screening serum analytes and amniocentesis can affect perinatal outcomes via mood
      based alterations in blood flow of the uterine arteries and the screening markers
      beta-hCG,unconjugated estriol, and alpha-fetoprotein.

PMID- 30291696
TI  - Expression of Ghrelin and Its Receptor mRNA in Bovine Oocyte and Cumulus Cells.
AB  - Energy balance is regulated by ghrelin which is a neuroendocrine modulator.
      Ghrelin is expressed in reproductive organs. However, the role of ghrelin during
      in vitro maturation (IVM) and bovine preimplantational development is limited.
      The purpose of this study was to measure the expression of ghrelin (GHRL) and its
      receptor growth hormone secretagogue receptor 1A (GHS-R1A) mRNA, and determine
      cumulus oocyte complex (COC) viability after IVM with 0, 20, 40 and 60 pM of
      ghrelin. Also, pronuclear formation was recorded after in vitro fertilization
      (IVF). GHRL and GHS-R1A mRNA expression in oocyte and cumulus cells (CCs) was
      assessed using reverse transcription-polymerase chain reaction (PCR). Oocyte and
      CC viability were analyzed with the fluorescein diacetate fluorochrome-trypan
      blue technique. Pronuclear formation was determined 18 hours after IVF with
      Hoechst 33342. The results demonstrated that ghrelin mRNA is present in oocyte
      and CCs before and after 24 hours IVM with all treatments. Ghrelin receptor, GHS
      R1A, was only detected in oocytes and CCs after 24 hours IVM with 20, 40 and 60
      pM of ghrelin. Oocyte viability was not significantly different (P=0.77) among
      treatments. However, CC viability was significantly lower (P=0.04) when COCs were
      matured with ghrelin (77.65, 72.10, 66.32 and 46.86% for 0, 20, 40, and 60 pM of
      ghrelin, respectively). The chance of two pronuclei forming were higher (P=0.03)
      when ghrelin was not be added to the IVM medium. We found that ghrelin negatively
      impacts CC viability and pronuclear formation.

PMID- 30291697
TI  - COMFFETI, Combined Fresh and Frozen Embryo Transfers per Individual: A New Index
      of Quality Control for The Performance of emberyologic Labs in The Emerging Era
      of Segmentation of Cycle and Freeze-All Strategy.
AB  - The efficacy of in vitro fertilization (IVF) for treating human infertility has
      only one final efficacy index and that is the achievement of a delivery. However,
      with the evolution of the freeze-all strategy, a new problem is arising for
      evaluating the performance of an embryological team. The aim of the study was to
      present a new representative index, combining fresh and frozen embryo transfer
      success rates. In this opinion article, apart from the effectiveness of managing
      fresh gametes and embryos, we wish to evaluate the efficacy of the processes of
      both freezing and thawing of the produced embryos. The reporting of pregnancy
      rates of an IVF unit in the past was primarily laying in the fresh embryo
      transfer (ET) pregnancy rates. Now with the most frequent utilization of freeze
      all strategy, it does not seem logical to report only on poor prognosis patients
      as all the good cases are postponed for thawed cycles. Ongoing implementation of
      the freeze-all strategy has indicated the need to establish a new representative
      index that may combine the success of both fresh and frozen cycles performed in
      the same woman; an index that may not be biased by the policy of an IVF center
      towards or against the freeze-all strategy. This newly proposed index, which is
      referred to as COMFFETI (Combined Fresh #38; Frozen Embryo Transfers per
      Individual), describes the optimal way to report final reproductive outcomes in
      the present opinion article.

PMID- 30291699
TI  - Humanities in the undergraduate medical and midwifery curriculum: a descriptive
      Italian comparative study.
AB  - There is an increasing emphasis on humanized care in obstetric and midwifery
      practice. The goal of this paper is to investigate if and how medical humanities
      content was present in the undergraduate medical syllabus and how similar or
      different this is from the undergraduate midwifery program in Italy. A review of
      the 2017-18 curriculum for Italian Schools of Medicine and of Midwifery was
      carried out through institutional websites or mailing requests. The following
      details were collected for each program: the type of humanities content; the
      academic credits allocated, whether it was taught as a stand-alone (independent)
      topic or not, and the year(s) of the program when it was provided. Programs were
      included for 39 Schools of Medicine and 36 Schools of Midwifery. All midwifery
      schools included at least one subject with humanities content. Five medical
      schools (12.9) did not appear to have any subjects in this area. Psychology and
      ethics/bioethics were the most frequently found topics in both disciplines, but,
      apart from history of medicine, midwifery was much more likely than medicine to
      include other humanities topics, and especially pedagogy, anthropology, sociology
      and communication studies, philosophy and cross-cultural studies were rarely or
      never included in either discipline. A greater breadth of humanities studies was
      included in midwifery schools. However, their relative importance appears to be
      low, given the low level of academic credits and lack of presence as independent
      subjects.

PMID- 30291698
TI  - Perspective review of what is needed for molecular-specific fluorescence-guided
      surgery.
AB  - Molecular image-guided surgery has the potential for translating the tools of
      molecular pathology to real-time guidance in surgery. As a whole, there are
      incredibly positive indicators of growth, including the first United States Food
      and Drug Administration clearance of an enzyme-biosynthetic-activated probe for
      surgery guidance, and a growing number of companies producing agents and imaging
      systems. The strengths and opportunities must be continued but are hampered by
      important weaknesses and threats within the field. A key issue to solve is the
      inability of macroscopic imaging tools to resolve microscopic biological disease
      heterogeneity and the limitations in microscopic systems matching surgery
      workflow. A related issue is that parsing out true molecular-specific uptake from
      simple-enhanced permeability and retention is hard and requires extensive
      pathologic analysis or multiple in vivo tests, comparing fluorescence
      accumulation with standard histopathology and immunohistochemistry. A related
      concern in the field is the over-reliance on a finite number of chosen
      preclinical models, leading to early clinical translation when the probe might
      not be optimized for high intertumor variation or intratumor heterogeneity. The
      ultimate potential may require multiple probes, as are used in molecular
      pathology, and a combination with ultrahigh-resolution imaging and image
      recognition systems, which capture the data at a finer granularity than is
      possible by the surgeon. Alternatively, one might choose a more generalized
      approach by developing the tracer based on generic hallmarks of cancer to create
      a more "one-size-fits-all" concept, similar to metabolic aberrations as exploited
      in fluorodeoxyglucose - positron emission tomography (FDG-PET) (i.e., Warburg
      effect) or tumor acidity. Finally, methods to approach the problem of production
      cost minimization and regulatory approvals in a manner consistent with the
      potential revenue of the field will be important. In this area, some solid steps
      have been demonstrated in the use of fluorescent labeling commercial antibodies
      and separately in microdosing studies with small molecules.

PMID- 30291700
TI  - Optimal outcomes and women's positive pregnancy experience: a comparison between
      the World Health Organization guideline and recommendations in European national
      antenatal care guidelines.
AB  - BACKGROUND: The publication of the World Health Organization (WHO)
      recommendations on antenatal care in 2016 introduced the perspective of women as
      a necessary component of clinical guidelines in maternity care. WHO highlights
      the crucial role played by evidence-based recommendations in promoting and
      supporting normal birth processes and a positive experience of pregnancy. This
      paper aims to explore and critically appraise recommendations of national
      antenatal care guidelines across European countries in comparison with the WHO
      guideline. METHODS: We collected guidelines from country partners of the EU COST
      Action IS1405. Components of the documents structure and main recommendations
      within and between them were compared and contrasted with the WHO guideline on
      antenatal care with a particular interest in exploring whether and how women's
      experience was included in the recommendations. RESULTS: Eight out of eleven
      countries had a single national guideline on antenatal care while three countries
      did not. National guidelines mostly focused on care of healthy women with a
      straightforward pregnancy. The level of concordance between the national and the
      WHO recommendations varied along a continuum from almost total concordance to
      almost total dissonance. Women's views and experiences were accounted for in some
      guidelines, but mostly not placed at the same level of importance as clinical
      items. CONCLUSIONS: Findings outline convergences and divergences with the WHO
      recommendations. They highlight the need for considering women's views more in
      the development of evidence-based recommendations and in practice for positive
      impacts on perinatal health at a global level, and on the experiences of each
      family.

PMID- 30291701
TI  - Ovarian tumors secreting androgens: an infrequent cause of hyperandrogenism.
AB  - INTRODUCTION: The sex cord-stromal tumors are relative rare, comprising 5-8% of
      all ovarian neoplasms. OBJECTIVE: Review of 13 cases of androgen tumors and a
      description of 3 cases: Leydig tumor, steroid cell (NOS) tumor and Sertoli-Leydig
      tumor. RESULTS: Twelve patients were menopausal and one patient of reproductive
      age. In all cases, regardless of the histological variety, women presented
      symptoms of hyperandrogenism and virilization. All had increased values of total
      testosterone. In all cases surgical treatment was performed, with favorable
      clinical and biochemical evolution. CONCLUSIONS: Sex cord stromal tumors of the
      ovary are rare, and can be characterized by virilization for most patients. The
      majority of the tumors are benign, with few cases having low-grade malignancy.
      The suspicion and correct evaluation of these women will lead to an early
      diagnosis and improve their quality of life.

PMID- 30291702
TI  - Effectiveness, quality of life and sexual functions in women with anterior
      compartment prolapse treated by native tissue repair: a mini-review.
AB  - Anterior compartment defect is the most common pelvic organ prolapse. It is
      defined as the descent of the bladder into the anterior vaginal wall. The
      etiology is multifactorial and the main risk factors are vaginal delivery and
      conditions associated with increased abdominal strain. Aging is significantly
      associated with the prevalence and severity of pelvic organ prolapse. Treatment
      may be conservative or surgical according to symptoms, prolapse degree and not
      forgetting both patient and doctor preferences. The aim of this work is to
      identify the most efficient surgical treatment of cystocele and its recurrences.
      There are two different surgical approaches for the treatment of cystocele:
      traditional repair and mesh repair. Prosthetic treatment gives higher anatomical
      success rate but traditional anterior repair has less complication demonstrating
      a lower risk of reoperation. Surgical treatment in general improves both the
      quality of life and the sexual function. We carried out a research on the impact
      of the anterior defect before and after native tissue surgery on quality of life
      and sexual function. The efficacy and complications of the treatment were also
      assessed.

PMID- 30291703
TI  - Fulminant Staphylococcal Infections.
AB  - Fulminant staphylococcal infection indicates an explosive, intense, and severe
      infection occurring in a patient whose previous condition and antecedent would
      never have caused any anticipation of life-threatening development. This includes
      necrotizing pneumonia, necrotizing fasciitis, and to some extent toxic shock
      syndrome and infective endocarditis. In the three former diseases, toxin
      production plays a major role whereas in the latter (fulminant presentation of
      infective endocarditis), association with any particular toxinic profile has
      never been demonstrated. This article reviews the clinical, pathophysiological,
      and therapeutic aspects of these diseases.

PMID- 30291705
TI  - Physician Compensation, Accountability and Performance in Canada: Changing the
      Pas de Deux.
AB  - Physician bargaining with provincial governments has been a challenge in the
      provinces of Canada since the origins of medicare, when this bilateral
      negotiation first began in Saskatchewan and was eventually codified in the Canada
      Health Act. In recent years, the emergence of accountability for performance has
      become a central policy focus in advanced countries to raise the bar on the
      quality and value of physician services and their effective integration within
      the broader healthcare system. The challenge has been to create real
      accountability while balancing growth in physician incomes with fiscal capacity
      and affordability. This commentary reflects a rich variety of perspectives from
      our contributing authors. It also lays out a number of challenges and changes
      that may be required to strengthen the importance of accountability for fair
      payments within Canadian medicare.

PMID- 30291706
TI  - Doctors and Canadian Medicare: Improving Accountability and Performance.
AB  - Physician compensation has been a rapidly growing segment of healthcare costs in
      Canada since the late 1990s. In comparative terms, Canadian physicians are now
      well compensated compared to physicians in other high-income countries. This has
      caused provincial governments to begin constraining physician remuneration.
      However, physician payment should be examined in a larger governance context,
      including the potentially changing role of physicians, as provincial governments
      try to improve quality, increase coordination and improve overall health system
      performance. Although limited progress has been made through primary care reforms
      in a few jurisdictions, substantive improvement has been hampered by a
      misalignment between the policy goals and intentions of provincial governments
      and existing governance and accountability structures. This creates an
      environment in which both administrators and physicians feel they have limited
      input or control, seeding an adversarial rather than a collaborative
      relationship. Effective reform will require addressing governance and
      accountability at the same time as physician payment.

PMID- 30291707
TI  - Physician Service Costs: Is There Blame to Share Around?
AB  - The rising portion of national income devoted to healthcare in general and the
      portion allocated to physician services have been a focus of the health policy
      literature for some time. Greater recognition should be given to the fact that
      the observed trends in physician service expenditures are the product of the
      interaction between physicians and provincial governments. Improving the
      productivity of healthcare systems in the delivery of high-quality primary care
      will require moving beyond simple oversight to deeper engagement with physicians
      as partners in system improvement.

PMID- 30291704
TI  - Mycobacteriophages.
AB  - Mycobacteriophages are viruses that infect mycobacterial hosts. A large number of
      mycobacteriophages have been isolated and genomically characterized, providing
      insights into viral diversity and evolution, as well as fueling development of
      tools for mycobacterial genetics. Mycobacteriophages have intimate relationships
      with their hosts and provide insights into the genetics and physiology of the
      mycobacteria and tools for potential clinical applications such as drug
      development, diagnosis, vaccines, and potentially therapy.

PMID- 30291708
TI  - Healthcare Delivery and Physician Accountability in Quebec: A System Ready for
      Change.
AB  - In hindsight, there have been unintended systemic consequences stemming from the
      traditional roles physicians have assumed and the structures within which they
      have been permitted to organize themselves. It is critical that the national
      discussion take account of this because we must reconcile ourselves to the
      current reality in which all other allied healthcare professionals are practising
      at "the top of their licence." Furthermore, the pace of technological change,
      especially the deciphering of the genome and the digitalization of virtually
      everything, has engendered a revolution characterized by the democratization of
      knowledge and technology, so that the point of care will be wherever the patient
      is. Dysfunctional reimbursement schemes and a lack of accountability are merely
      symptoms of a system that must change.

PMID- 30291709
TI  - Doctors and Canadian Medicare: Improving System Performance Requires System
      Change.
AB  - Many of the issues raised and insights provided by Marchildon and Sherar (2018)
      in their essay on doctors and Canadian medicare are on target. The inadequacy of
      available data on physician payment, however, calls into question the robustness
      of some interprovincial comparisons, and when it comes to compensation,
      comparisons to US physicians would be most relevant. In contrast to their
      assertion of a steadily increasing growth rate in physician expenditure, a more
      recent and longer view shows historically low growth in the past few years.
      Furthermore, the blame assigned to physicians and their medical associations
      needs to be shared with governments and most of all could be attributed to the
      lack of system structures and supports for improvement. New governance
      arrangements at the group or regional levels are needed but are insufficient in
      themselves. The additional features embodied in the Patient's Medical Home are
      essential for advancing primary care. Going even further, full population
      registration, greater availability of alternate payment arrangements, active
      participation of physicians in healthcare administration and support for
      meaningful measurement and feedback loops are among the changes required to
      transform Canadian medicare.

PMID- 30291710
TI  - Improving Physician Accountability through Primary Care Reform in Alberta.
AB  - Like other Canadian provinces and territories, Alberta has been attempting to
      reform primary care since the mid-1990s. Although initially these efforts were
      focused almost exclusively on the method of payment for physicians, since 2003,
      the focus of government policy has broadened to include other aspects of
      practice, including governance and accountability, improved continuity, the use
      of a team-based approach and the use of electronic information systems. Although
      significant progress has been made, Alberta continues to face challenges.

PMID- 30291711
TI  - From Autonomous Gatekeepers to System Stewards: Can the Alberta Agreement Change
      the Role of Physicians in Canadian Medicare?
AB  - Marchildon and Sherar's (2018) "Doctors and Canadian Medicare" presents a
      specific dilemma for healthcare reform: the ability of physicians to negotiate
      ever-increasing incomes without reference to the consequences to healthcare costs
      or provincial budgeting. This commentary situates that discussion in the broader
      debate of the challenges to healthcare reform as exemplified by studies such as
      Paradigm Freeze (Lazar et al. 2013) and the ability of provincial medical
      associations to act as both system insiders (gatekeepers) and outsiders (with no
      responsibility for system finances). The resolution to this dilemma may be to
      follow the lead of the Alberta government by negotiating a stewardship role for
      physicians that requires them to take broader governmental goals into account.
      There is evidence to suggest that physicians may be the best actors to insist on
      and enforce changes in physician behaviour. Furthermore, adding physicians as
      stewards of the system may help create better checks and balances in the
      currently dysfunctional dynamics between federal and provincial stewards.

PMID- 30291712
TI  - Canada's Ailing Healthcare System: It's the Doctors' Fault?
AB  - The Marchildon and Sherar (2018) paper provides some useful insights: the role of
      primary care, improved approaches to physician compensation and the importance of
      accountability and governance. But their approach of focusing on doctors,
      including their compensation, misses the boat. Canada's healthcare system needs a
      major overhaul to improve integration and reward good performance for patient
      care going beyond medical practitioner compensation.

PMID- 30291713
TI  - Building on Primary Care Reforms and Indigenous Self-Determination in the
      Northwest Territories: Physician Accountability and Performance in Context.
AB  - This commentary responds to Marchildon and Sherar's (2018) paper, "Doctors and
      Canadian Medicare: Improving Accountability and Performance," in which they
      explore questions around governance and physician accountability in Canada. This
      response situates the issues raised in a northern context by sharing experiences
      with primary care reform in the Northwest Territories and exploring the
      implications these changes have had for physician accountability and reported
      system improvements. Physician leadership and accountability are further explored
      in the northern context, where health systems for Indigenous communities include
      multiple jurisdictions and transitions in governance advance the self-government,
      land claims and treaty rights of Indigenous peoples.

PMID- 30291714
TI  - Measuring Physicians' Incomes with a Focus on Canadian-Controlled Private
      Corporations.
AB  - Understanding physician remuneration and its growth is extremely complex, much
      more so than for a typical worker. Highlighting one narrow aspect of this issue,
      this paper focuses on governments' increased incentives for physicians to
      incorporate and the ensuing physician response in the period 1996-2011.
      Nationally, incorporation rates increased for both general practitioners and
      specialists between 1996 and 2011. We observe that the largest changes in
      provincial regulation were in Ontario, and incorporation increased from 18% in
      2001 to 54% five years later. Incorporation is less common in Quebec, where the
      incentives were the weakest. Married male physicians, middle-aged physicians
      (regardless of sex), physicians with higher incomes and physicians born outside
      of Canada are all more likely to incorporate their practices. On average,
      incorporated physicians realized a 4% reduction in personal income taxes and
      accumulated retained earnings of at least $10,000 per annum in their Canadian
      controlled private corporations in our data period. The benefits of incorporation
      stem largely from retained earnings and income splitting. Many physicians benefit
      from one or both; however, the benefits of incorporation are not equally
      distributed. Sex, marital status and income affect the magnitude of the financial
      benefit of incorporation.

PMID- 30291715
TI  - Value for Money through Effective Stewardship.
AB  - The respondents all raised valuable, informative points in response to our
      Invited Essay. There was convergence around the need to alter governance
      structures at the same time as payment arrangements for physicians to achieve
      higher-performing health systems within Canada. At the same time, there were
      different views on how best to address the disconnect between levels of physician
      remuneration and accountability for healthcare performance and delivery. In
      addition to ongoing efforts to improve governance, such as the recent amendments
      to the government-physician agreement in Alberta, individual provincial
      governments can and should take the lead in initiating and evaluating further
      payment and governance experiments.

PMID- 30291717
TI  - A five-compartment biokinetic model for 90 Y-DOTATOC therapy.
AB  - PURPOSE: Neuroendocrine tumors (NETs) are now routinely treated by radiopeptide
      targeted therapy using somatostatin receptor-binding peptides such as 90 Y- and
      177 Lu-DOTATOC. The objective of this work was to develop a biokinetics model of
      90 Y labelled DOTATOC, which is applied in the therapy of NETs to estimate doses
      in kidney and tumor. METHODS: A multi-compartment model described by two sets of
      differential equations, one set for the actual 30-min infusion and the other set
      for the post-infusion period was developed and activities were measured by liquid
      scintillation counting in blood (compartment 1) and the urine (compartment 3).
      The inter-compartment transfer coefficients, lambdaij , were varied to yield the
      best fit of the calculated to the measured time-activity data and the 90 Y
      DOTATOC time-activity data in the five-compartments comprising the human body
      were thus determined. The resulting time-activity curves were integrated over the
      interval from 0 to 72 h post administration to obtain the number of radioactive
      decays in each compartment and, in case of the kidneys and tumor, then multiplied
      by the self-dose 90 Y beta particle absorbed fraction, determined by Monte Carlo
      (MC) simulation, the kidney and tumor absorbed doses. RESULTS: Transfer
      coefficients lambdaij , were determined for five-compartments for all patients.
      Time- activity curves of 90 Y-DOTATOC in 14 patients were determined, and two
      typical ones are shown graphically. Absorbed doses in the tumor and kidneys,
      obtained by the developed method, were determined. The mean absorbed dose in a
      kidney per unit of administered activity is 1.43 mGy/MBq (range 0.73-2.42
      mGy/MBq). The tumor dose was determined as 30.94 mGy/MBq (range 20.05-42.31
      mGy/MBq). CONCLUSION: Analytical solution of a biokinetic model for 90 Y-DOTATOC
      therapy enabled determination of the transfer coefficients and derivation of time
      activity curves and kidney and tumor absorbed doses for 14 treated patients. The
      model can be applied to other radionuclides where elimination is predominantly
      through urine, which is often the case in radiopharmaceuticals.

PMID- 30291716
TI  - Peptic Ulcer Is the Most Common Cause of Non-Variceal Upper-Gastrointestinal
      Bleeding (NVUGIB) in China.
AB  - BACKGROUND This study aimed to discover the common cause of non-variceal upper
      gastrointestinal bleeding (NVUGIB) by conducting a multi-center retrospective
      study from 2008 to 2012. MATERIAL AND METHODS Hospitalized patients ages >=18
      years old, from 8 hospitals in China, diagnosed with NVUGIB by endoscopy from 1
      January 2008 to 31 December 2012 were enrolled. Questionnaires were developed and
      a data-entry graphical user interface was designed by using EpiData software.
      RESULTS Total of 2977 hospitalized patients from 8 medical centers were included.
      A total of 95.47% (2842/2977) of patients were admitted to a general ward, 3.53%
      (105/2977) were admitted to an emergency ward, and 1.00% (31/2977) were admitted
      to an intensive care unit. Peptic ulcer remained the most common cause of NVUGIB
      (73.26%), but there was a declining trend in its constituent ratio, from 2008 to
      2012. A total of 14.41% (429/2977) of patients had co-morbid conditions, 92.85%
      (2764/2977) used proton-pump inhibitors (PPIs) prior to endoscopic treatment,
      19.65% (585/2977) underwent emergency endoscopy, and 23.45% (698/2977) received a
      transfusion of red blood cell suspensions. A total of 5.34% (159/2977) underwent
      endoscopic therapy, with a treatment rate of 16.9% in high-risk peptic ulcer
      patients (96/568). A total of 7.69% (237/2977) were administered aspirin, of whom
      32.50% (77/237) resumed aspirin intake after gastrointestinal bleeding was
      controlled. The median length of hospitalization was 8 days (IQR, 5-11) and the
      mortality rate was 1.71% (51/2977). CONCLUSIONS Peptic ulcer was still the most
      common cause of NVUGIB in China. The proportion of patients with high-risk peptic
      ulcer bleeding who received endoscopic therapy was 16.9%. Only 19.65% of NVUGIB
      patients underwent emergency endoscopy.

PMID- 30291718
TI  - Infimal convolution-based regularization for SPECT reconstruction.
AB  - PURPOSE: Total variation (TV) regularization is efficient in suppressing noise,
      but is known to suffer from staircase artifacts. The goal of this work was to
      develop a regularization method using the infimal convolution of the first- and
      the second-order derivatives to reduce or even prevent staircase artifacts in the
      reconstructed images, and to investigate if the advantage in noise suppression by
      this TV-type regularization can be translated into dose reduction. METHODS: In
      the present work, we introduce the infimal convolution of the first- and the
      second-order total variation (ICTV) as the regularization term in penalized
      maximum likelihood reconstruction. The preconditioned alternating projection
      algorithm (PAPA), previously developed by the authors of this article, was
      employed to produce the reconstruction. Using Monte Carlo-simulated data, we
      evaluate noise properties and lesion detectability in the reconstructed images
      and compare the results with conventional total variation (TV) and clinical EM
      based methods with Gaussian post filter (GPF-EM). We also evaluate the quality of
      ICTV regularized images obtained for lower photon number data, compared with
      clinically used photon number, to verify the feasibility of radiation-dose
      reduction to patients by use of the ICTV reconstruction method. RESULTS: By
      comparison with GPF-EM reconstructed images, we have found that the ICTV-PAPA
      method can achieve a lower background variability level while maintaining the
      same level of contrast. Images reconstructed by the ICTV-PAPA method with 80,000
      counts per view exhibit even higher channelized Hotelling observer (CHO) signal
      to-noise ratio (SNR), as compared to images reconstructed by the GPF-EM method
      with 120,000 counts per view. CONCLUSIONS: In contrast to the TV-PAPA method, the
      ICTV-PAPA reconstruction method avoids substantial staircase artifacts, while
      producing reconstructed images with higher CHO SNR and comparable local spatial
      resolution. Simulation studies indicate that a 33% dose reduction is feasible by
      switching to the ICTV-PAPA method, compared with the GPF-EM clinical standard.

PMID- 30291719
TI  - Instruments evaluating the clinical findings of laryngopharyngeal reflux: A
      systematic review.
AB  - OBJECTIVES: To identify the instruments for evaluating the clinical findings
      (ICFs) of laryngopharyngeal reflux (LPR) designed for use with regard to
      diagnosis and treatment effectiveness. METHODS: The PubMed, Scopus, and Cochrane
      databases were used to search for subject headings following Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Three
      investigators retrieved relevant studies published between 1990 and 2018
      describing the evolution of laryngopharyngeal findings throughout LPR treatment.
      Issues of clinical relevance, that is, LPR diagnosis, treatments, and signs
      assessed for diagnosis or as therapeutic outcomes, were assessed. The
      investigators also evaluated the psychometric properties (conceptual model,
      content validity, consistency, reliability, concordance, convergent validity,
      known-groups validity, responsiveness to change, and interpretability) of the
      ICF. The risk of bias was assessed with the tool of the Clarity Group and
      Evidence Partners. RESULTS: The search identified 1,227 publications with a total
      of 4,735 LPR patients; of these studies, 53 met the inclusion criteria. Of these
      53 studies, we identified 10 unvalidated and six validated ICFs. None of the
      validated ICFs included all the psychometric properties. The main identified
      deficiencies related to ICF psychometric validation included variable construct
      validity, disparate and uncertain reliabilities, and a lack of interpretability.
      The lack of consideration of certain LPR laryngeal and extralaryngeal signs is
      the main weakness of ICFs, biasing content, and construct validities. CONCLUSION:
      The low specificity of LPR signs, the lack of consideration of many findings, and
      the absence of a gold standard for diagnosis constitute barriers to the further
      validation of these ICFs. Additional studies are needed to develop complete and
      reliable ICFs. Laryngoscope, 2018.

PMID- 30291720
TI  - Convergence between Rorschach and self-report: A new look at some old questions.
AB  - OBJECTIVE: This study presents an examination of the influence of response format
      on convergence between performance-based and self-report assessments of similar
      mental health constructs, to determine if such method variance might account for
      prior findings of lack of relationship. METHODS: An online sample of 455
      participants (57% male; average age, 35.5) completed a multiple-choice version of
      the Rorschach and two self-report instruments, the Personality Assessment
      Inventory (PAI) and the International Personality Item Pool (IPIP) representation
      of the domain traits of the five-factor model (FFM). RESULTS: Several significant
      interrelationships emerged between the Rorschach Amplified Multiple Choice Test
      and the PAI and IPIP five-factor scales. CONCLUSIONS: These findings suggest that
      the Rorschach can correlate meaningfully with similar constructs assessed using
      self-report methodology when comparable response formats are utilized.

PMID- 30291721
TI  - Pilot evaluation of a targeted intervention for peer-victimized youth.
AB  - OBJECTIVE: Due to the limited effectiveness of extant prevention and intervention
      strategies, the current study is an initial evaluation of a cognitive behavioral
      group intervention, originally designed to treat symptoms of depression and
      anxiety, for youth who experienced peer victimization. METHODS: Twelve third-
      through fifth-grade youth participated in the intervention, and their data were
      compared with 12 youth who were a part of a naturalistic control group.
      Additionally, school-wide data are reported to provide overall school trends.
      RESULTS: Whereas the intervention group participants exhibited decreases in
      relational victimization, depressive symptoms, and passive coping, the control
      group participants exhibited nonsignificant increases in relational
      victimization, depressive symptoms, and passive coping. School-wide data also
      indicated overall increases in relational victimization and depressive symptoms,
      but no changes in passive coping. CONCLUSION: Findings suggest that cognitive
      behavioral group interventions may provide a promising avenue for addressing the
      mental health needs of victimized elementary school-age youth.

PMID- 30291722
TI  - Vps74p controls Golgi size in an Arf1-dependent manner.
AB  - The oncogene GOLPH3 is implicated in Golgi size regulation, a function yet to be
      experimentally linked to its PI4P effector function or the Golgi cisternal
      maturation in general. Moreover, its yeast homolog, Vps74p is not yet implicated
      in Golgi size regulation. Our results indicate that VPS74 deletion increases the
      late Golgi cisternal size and the cisternal maturation frequencies, and
      destabilizes the Golgi PI4P gradient in budding yeast. Overexpression of Arf1 can
      suppress this cisternal enlargement and increased maturation frequency phenotype
      of ?vps74. ?arf1 alters Vps74p and PI4P distribution along the Golgi stacks. We
      conclude that Vps74p, the downstream effector of Arf1, regulates Golgi size by
      altering its cisternal maturation frequency and by maintaining the PI4P
      distribution along the Golgi compartments.

PMID- 30291723
TI  - MicroRNA miR-181a/b-1 controls MAIT cell development.
AB  - Mucosal-associated invariant T (MAIT) cells constitute a major fraction of innate
      like T cells in humans with critical roles in defense against microbial pathogens
      and in maintaining mucosal integrity. However, the molecular mechanisms
      underlying MAIT cell development remain largely elusive. Here we investigated the
      role of miR-181a/b-1, a pair of microRNAs that serve as rheostat of TCR signal
      strength, in this process. Loss of miR-181a/b-1 in mice resulted in a profound
      arrest in early MAIT cell development. As a consequence, in the absence of miR
      181a/b-1, thymic MAIT cells failed to acquire functional maturity based on
      expression of transcription factors PLZF, T-bet and RORgammat. Temporal analysis
      of development using a molecular timer in combination with loss of miR-181a/b-1
      revealed that MAIT cells complete functional maturation in the periphery and
      indicates that functionally mature MAIT cells in the thymus are long-term
      resident cells. Thus, our study provides insight into the dynamics of MAIT cell
      development in vivo. Of note, deletion of miR-181a/b-1 alone completely mirrored
      loss of all miRNAs.

PMID- 30291724
TI  - Sensitivity of the IQM transmission detector to errors of VMAT plans.
AB  - PURPOSE: The integral quality monitor (IQM) transmission detector is a wedge
      shaped large area ionization chamber that reports a position-weighted dose area
      product for each control point of an IMRT or VMAT plan. In this study, the
      accuracy of the signal prediction is verified for the Synergy Agility MLC.
      Tolerance criteria for VMAT plan verification with the IQM were obtained from the
      observed sensitivity for the detection of incorrectly delivered plans. METHODS:
      The predicted IQM signal was compared to the measured signal recorded for a set
      of 30 VMAT plans for each beam quality of 6 and 10 MV. The system's capability to
      detect incorrectly delivered plans was tested by measuring altered plans
      containing small, random deviations. In addition, the observed deviations were
      related to measurements performed with a second QA phantom. RESULTS: The
      cumulative IQM signal per arc deviated from the respective calculation on average
      by -0.48% (6 MV) and +0.21% (10 MV) with a standard deviation of 1.08% in both
      cases, suggesting a 2% warning and 3% action threshold as plan acceptance
      criteria. This choice was confirmed by the optimum threshold of 2.5% obtained via
      receiver operating characteristic (ROC) analysis. Reproducibility of individual
      control points in multiply measured plans was low (on average 7% for 1SD) and
      thus, segment-by-segment comparison was impractical. A suitable criterion to
      resolve the angular distribution of the plan was identified by binning three to
      five control points as a running average. While the correlation between IQM
      signal deviations and gamma passing rates obtained with the ArcCHECK phantom was
      low for clinical plans, it was apparent for erroneous plans. Binning led to even
      higher sensitivity to errors. CONCLUSIONS: The IQM was able to detect induced
      errors at least as reliable as the standard phantom and showed the potential to
      be used in pretreatment plan verification to ensure the correct plan transfer and
      delivery. However, there is no direct correlation between the IQM signal
      deviation and DVH metrics, so the IQM should be primarily used to screen for
      errors. Finer diagnostics should then be carried out using a different phantom.

PMID- 30291725
TI  - Legends of allergy: Carla Bruijnzeel-Koomen.

PMID- 30291726
TI  - Caring for "Super-utilizers": Neoliberal Social Assistance in the Safety-net.
AB  - Hospitals throughout the United States are implementing new forms of care
      delivery meant to address social needs for structurally vulnerable patients as a
      strategy to prevent emergency department visits and hospitalizations and to
      thereby reduce costs. This article examines how the deployment of social
      assistance within a neoliberal institutional logic involves the negotiation and
      alignment of economistic values with ethics of care. We focus on care practices
      meant to stabilize the socioeconomic conditions of the most expensive patients in
      the health care system-the "super-utilizers"-through the provisioning of basic
      resources such as housing, food, transportation, and social support. These
      patients typically suffer from multiple chronic illnesses accompanied by
      conditions of poverty, housing and food insecurity, exposure to violence and
      trauma, and associated substance use and mental health problems. We offer an
      account of how practices of social assistance are being forged within contexts
      defined by neoliberal governance.

PMID- 30291727
TI  - Genetic characterization and diversity of porcine circovirus type 2 in non
      vaccinated South African swine herds.
AB  - The porcine circovirus type 2 (PCV2) is a swine infectious viral pathogen of
      great significance in global swine herds. It was recently detected at another
      Province of South Africa sequel to the first detection of North American-like
      strain (PCV2a) at Gauteng about two decades ago, but there is a dearth of
      information about the genomic features and diversity of the viral strains in
      circulation within the country and the entire sub-Saharan Africa region. To date,
      only one complete genome of the virus from South Africa is available on global
      data base. This current effort is therefore geared towards the full-genome
      characterization of the circulating PCV2 strains in the pigs of Eastern Cape
      Province. With the use of conventional polymerase chain reaction method, fifteen
      complete PCV2 genomes were successfully amplified, sequenced and assembled from
      field samples obtained from non-vaccinated pigs in the region. Neighbor Joining
      and Maximum Likelihood phylogenetic analyses of the ORF2 gene and full genomes
      unanimously showed that most of the assembled genomes (11) belong to genotype
      PCV2b. Furthermore, three of the characterized sequences formed clade with other
      reference mutant PCV2b and PCV2b subtype 1C (i.e. PCV2d) strains from the USA,
      China and South Korea. The last sequence, however, clustered with other reference
      strains belonging to PCV2 intermediate clade 2 (PCV2-IM2), recently identified in
      a global PCV2 strains phylogenetic analysis. This study reports the first
      complete genome sequences of PCV2b, PCV2d and PCV2-IM2 in pigs from South Africa,
      and it gives a possible insight into the genetic characteristics and variability
      of the viral strains presently in circulation within the country. It further
      emphasizes the need for more stringent measures in curtailing the introduction
      and spread of transboundary swine pathogens in the country and entire Southern
      African region.

PMID- 30291728
TI  - Predicting outcomes and complications following radioiodine therapy in Graves'
      thyrotoxicosis.
AB  - OBJECTIVE: Radioiodine (RAI) is an effective treatment for Graves' thyrotoxicosis
      but is associated with a failure rate of 15% and may be a risk factor for thyroid
      eye disease (TED) and weight gain. We sought to examine predictors of RAI
      failure, weight gain, TED and patient satisfaction. DESIGN: Retrospective cohort
      study. PATIENTS: A total of 655 episodes of RAI in Graves' thyrotoxicosis
      patients (2006-2015). MEASUREMENTS: Biochemical assessment, including TFTs and
      thyrotropin receptor antibodies (TRAb), clinical features (eg, TED, weight and
      thionamide use) and patient questionnaire. RESULTS: The treatment failure rate
      was 17%. Failure was greater with higher fT4 (P = 0.002) and higher TRAb (P =
      0.004). Failure rate was 42.2% when TRAb >40 U/L. Median weight gain was 3.2 kg
      in those with normal fT4 prior to RAI and 5.8 kg when fT4 was elevated (P <
      0.001). New TED developed in 7.6% but was not associated with post-RAI
      dysthyroidism. Treatment satisfaction was generally high (median response 8/10).
      CONCLUSIONS: Treatment failure after RAI occurs in predictable groups and this
      should be reflected in the information provided to patients. Weight gain is
      common and may not entirely be explained by a return to pre-thyrotoxic baseline.
      We were unable to detect any significant impact of post-RAI dysthyroidism on
      weight gain, TED or thyroid symptoms in this large cohort.

PMID- 30291729
TI  - Clearance of facial tattoo with triple-wavelength picosecond laser and
      fractionated carbon dioxide laser.

PMID- 30291730
TI  - Bifunctional anticaries peptides with antibacterial and remineralizing effects.
AB  - OBJECTIVES: Initial dental caries often occurs in clinic. Reduction of cariogenic
      bacteria and promotion of remineralization are effective ways to control them.
      This study was to develop bifunctional anticaries peptides with antibacterial and
      remineralizing properties. METHODS: We designed peptides TDH19, TNH19, and TVH19
      and selected one through comparing their minimal inhibitory concentrations (MICs)
      and minimal bactericidal concentrations (MBCs) against Streptococcus mutans and
      their reaction on mineralization. Then the bifunction of the selected peptide was
      studied through: (a) effects on S. mutans biofilm, (b) remineralizing effects on
      initial lesions and (c) stability in saliva and cytocompatibility to human oral
      keratinocytes (HOKs). RESULTS: TVH19 showed the lowest MIC and MBC and a better
      mineralizing ability. It inhibited new biofilm formation and reduced the
      viability of old biofilm (p < 0.05). Treating initial caries with TVH19 led to
      greater recovery of surface microhardness, shallower lesion depth, and higher
      mineral content (p < 0.05). No significant differences were observed between
      TVH19 and NaF samples (p > 0.05). TVH19 was stable in saliva and had little
      effect on HOKs. CONCLUSIONS: The novel bifunctional anticaries peptide TVH19 was
      developed with remarkable antibacterial activity and the potential to enhance
      remineralization of initial caries.

PMID- 30291731
TI  - Autophagy inhibition-enhanced assembly of the NLRP3 inflammasome is associated
      with cisplatin-induced acute injury to the liver and kidneys in rats.
AB  - The nucleotide-binding oligomerization domain-like receptor family, pyrin domain
      containing 3 (NLRP3) inflammasome has a key role in the inflammatory response. We
      found that cisplatin (7.5, 15 mg/kg, IV) could induce acute injury to the liver
      and kidneys of rats. Western blot and immunohistochemical analyses showed that
      expression of NLRP3, caspase-1 and interleukin-1beta was upregulated
      significantly in a dose-dependent manner after cisplatin exposure. Autophagy
      could inhibit NLRP3 expression and assembly of the NLRP3 inflammasome. Expression
      of light chain 3 II/I and p62 suggested that autophagy was inhibited during
      injury to the liver and kidneys. These data suggested that cisplatin might
      activate NLRP3 by inhibiting autophagy in the liver and kidneys of rats.

PMID- 30291732
TI  - Isolation and genetic characterization of H13N8 low pathogenic avian influenza
      virus from migratory birds in eastern China.
AB  - Low pathogenic avian influenza virus (LPAIV) is an important zoonotic pathogen.
      Migratory birds are the natural reservoir for all 16 haemagglutinin (HA) and nine
      neuraminidase (NA) subtypes of LPAIV. Surveillance of LPAIV in migratory
      waterfowl and poultry is important for animal and public health. An understanding
      of the ecology and epidemiology of LPAI viruses in their reservoirs is beneficial
      for routine surveillance projects. Here, we report the isolation of an H13N8
      LPAIV from black-tailed gulls in eastern China. Full genome sequences of this
      isolate were determined. Genetic analysis of the HA and NA segments of this
      isolate showed that this H13N8 LPAIV was derived from the Eurasian lineage.
      Additionally, we speculate that this H13N8 LPAIV was a reassortant between the
      North American and Eurasian lineages. Interestingly, we identified amino acid
      motifs responsible for increased virulence or transmission of influenza viruses
      in mammals. We also found weak but measurable haemagglutination inhibition
      antibody titers against H13N8 virus in serum samples collected from chickens.
      These results suggest that continued surveillance for LPAI viruses in migratory
      birds and poultry is required.

PMID- 30291733
TI  - Measurement of factor VIII activity of efraloctocog alfa with commercially
      available one-stage clotting and chromogenic assays: Results from the Belgian
      national External Quality Assessment Scheme.

PMID- 30291735
TI  - Nebivolol enhances the effect of alendronate against methylprednisolone-induced
      osteoporosis in rats.
AB  - This study aimed to assess the possible modulatory effect of nebivolol against
      methylprednisolone-induced osteoporosis in rats. Weekly administration of
      methylprednisolone (7 mg/kg), for six consecutive weeks caused significant
      increases in serum calcium, bone malondialdehyde, and hydroxyproline as well as
      serum alkaline phosphatase, but it significantly decreased serum phosphorous and
      osteocalcin, bone reduced glutathione, and nitric oxide (NO) as well as bone
      antioxidant enzymes activities compared with the control group. The results were
      confirmed by histopathological findings of femur bone. On the other hand,
      administration of alendronate (1 mg/kg) with nebivolol (1.5 mg/kg) orally and
      daily for seven consecutive days after methylprednisolone treatment caused marked
      mitigation in the above-mentioned parameters compared with methylprednisolone
      group. In conclusion, nebivolol proved to enhance the effect of alendronate in
      modulating methylprednisolone osteoporotic effect, which might be attributed to
      its release of NO together with its profound reducing capability in the oxidative
      cascade of bone tissue.

PMID- 30291736
TI  - Common health problems in safety-net primary care: Modeling the roles of trauma
      history and mental health.
AB  - OBJECTIVE: This study described trauma exposure and investigated mediational
      effects of mental health on the relationships between trauma and pain, sleep,
      smoking, and general health. METHOD: Participants were 210 low-income primary
      care patients. The study used a crosssectional, self-report survey design.
      RESULTS: Eighty-five percent of the sample reported adult trauma and 54% reported
      four or more childhood traumas. Moderate or higher depression and anxiety levels
      were present in 59% and 48% of participants, respectively. Structural equation
      model fit was good for sleep, pain, and general health, showing that trauma
      indirectly affected health variables via mental health. CONCLUSIONS: Participants
      endorsed substantial adult and childhood trauma, which likely had cascading
      effects on mental health and common primary care presenting health issues.

PMID- 30291737
TI  - Stimulation of the subparafascicular thalamic nucleus modulates dopamine release
      in the inferior colliculus of rats.
AB  - Although dopamine is commonly studied for its role in incentive motivation,
      cognition, and various neuropsychiatric disorders, evidence from Parkinson's
      disease (PD) patients that present auditory deficits suggest that dopamine is
      also involved in central auditory processing. It has been recently discovered
      that the subparafascicular thalamic nucleus (SPF) sends dopaminergic projections
      to the inferior colliculus (IC), an important convergence hub for the ascending
      and descending auditory pathways. In the present study, our aim was to provide
      neurochemical evidence that activation of SPF neurons evokes dopamine release in
      the IC of anesthetized rats using fast-scan cyclic and paired pulse voltammetry
      in combination with carbon fiber microelectrodes. Electrical stimulation of the
      SPF (60 and 90 Hz) evoked dopamine release in the IC in a frequency-dependent
      manner, with higher frequencies evoking greater amplitude dopamine responses.
      Optogenetic-evoked dopamine responses were similar to the effects of electrical
      stimulation suggesting that electrical stimulation-evoked dopamine release was
      not due to nonspecific activation of fibers of passage, but rather to activation
      of SPF cells projecting to the IC. Selective dopamine reuptake blockade enhanced
      the evoked dopamine response, while selective blockade of serotonin did not,
      confirming the selectivity of the neurochemical recordings to dopamine.
      Therefore, the SPF neuronal pathway functionally mediates dopamine release in the
      IC and thus may be involved in auditory processing deficits associated with PD.

PMID- 30291739
TI  - Making It Happen: Middle Managers' Roles in Innovation Implementation in Health
      Care.
AB  - BACKGROUND: Middle managers are given scant attention in the implementation
      literature in health care, where the focus is on senior leaders and frontline
      clinicians. AIMS: To empirically examine the role of middle managers relevant to
      innovation implementation and how middle managers experience the implementation
      process. METHODS: A qualitative study was conducted using the methods of grounded
      theory. Data were collected through semistructured interviews with middle
      managers (N = 15) in Nova Scotia and New Brunswick, Canada. Participants were
      purposively sampled, based on their involvement in implementation initiatives and
      to obtain variation in manager characteristics. Data were collected and analyzed
      concurrently, using an inductive constant comparative approach. Data collection
      and analysis continued until theoretical saturation was reached. RESULTS: Middle
      managers see themselves as being responsible for making implementation happen in
      their programs and services. As a result, they carry out five roles related to
      implementation: planner, coordinator, facilitator, motivator, and evaluator.
      However, the data also revealed two determinants of middle managers' role in
      implementation, which they must negotiate to fulfill their specific
      implementation roles and activities: (1) They perform many other roles and
      responsibilities within their organizations, both clinical and managerial in
      nature, and (2) they have limited decision-making power with respect to
      implementation and must work within the parameters set by upper levels of the
      organization. LINKING EVIDENCE TO ACTION: Middle managers play an important role
      in translating adoption decisions into on-the-ground implementation. Optimizing
      their capacity to fulfill this role may be key to improving innovation
      implementation in healthcare organizations.

PMID- 30291740
TI  - Cause of Death and End-of-Life Experiences in Individuals with Dementia with Lewy
      Bodies.
AB  - OBJECTIVES: To investigate the natural history, cause of death, and end-of-life
      experiences of individuals diagnosed with dementia with Lewy bodies (DLB).
      DESIGN: Twenty-question online survey administered through the Lewy Body Dementia
      Association. SETTING: United States. PARTICIPANTS: Caregivers, family, and
      friends of individuals who died in the past 5 years with a diagnosis of DLB
      (survey respondents: n = 658, 89% female, median age 50-69). MEASUREMENTS: The
      survey included 3 questions about the respondent's background and 17 about the
      end-of-life experiences of the person with DLB. Topics included time from symptom
      onset and diagnosis to death, cause of death, advance directive completion, end
      of-life education, hospice use, and location of death. Results were analyzed
      descriptively. RESULTS: Most individuals with DLB died within 5 years of
      diagnosis (median 3-4 years). Respondents indicated that physicians rarely
      discussed what to expect at the end of life (40% total, but only 22% to a helpful
      degree) and that the caregiver usually initiated such conversations. Death was
      usually expected, but fewer than half of respondents felt prepared for what to
      expect. Seventy-eight percent used hospice, usually at home or in skilled care,
      with wide variations in duration. Failure to thrive was the most common cause of
      death (65%), followed by pneumonia and swallowing difficulties (23%), other
      medical conditions (19%), and complications from falling (10%) (multiple causes
      allowed). CONCLUSION: Study results highlight a critical need for better
      prognostic counseling and education for persons and families living with DLB. The
      results of the current study can inform such counseling, but additional studies
      are needed to further explore expected prognosis of individuals diagnosed
      clinically with DLB and optimal use of palliative care services.

PMID- 30291741
TI  - Effects of psychosocial interventions on patient-reported outcomes in patients
      with psoriasis: a systematic review and meta-analysis.
AB  - BACKGROUND: Psoriasis can lead to high psychosocial burden, and the occurrence of
      psoriasis is related to psychological distress. OBJECTIVES: This study provides
      an overview of psychosocial interventions for patients with psoriasis and
      examines their effects on patient-reported outcomes. METHODS: A systematic search
      of four electronic databases (CENTRAL, MEDLINE, Embase and PsycINFO) was
      conducted in January 2017. All trials on psychosocial interventions for patients
      with psoriasis that used patient-reported outcomes and a comparison group were
      included. Data were extracted on intervention, study population and outcomes.
      Risk of bias was assessed according to the Cochrane Handbook. A meta-analysis on
      quality of life, depression and anxiety was performed. This review was registered
      on PROSPERO (CRD42016037934). RESULTS: Nineteen studies were included.
      Interventions primarily used cognitive behavioural or mindfulness-based
      techniques. Risk of bias was mostly rated 'unclear' due to nontransparent
      reporting (e.g. no study protocols were published, only one study reported
      blinding of patients). Meta-analysis using standardized mean differences between
      the intervention and control groups showed significant, small-to-medium effects
      (given with 95% confidence intervals) on quality of life (0.28, 0.04-0.51; six
      studies, n = 664) and anxiety (0.36, 0.15-0.57; six studies, n = 363). The effect
      on depression was not significant (0.37, -0.05 to 0.80; five studies, n = 326).
      CONCLUSIONS: Psychosocial interventions offer an effective means to improve
      quality of life and anxiety in patients with psoriasis. Although the importance
      of such psychosocial aspects for psoriasis is unquestioned, there is a lack of
      high-quality evaluation studies. Nontransparent reporting of risk of bias, low
      power and a lack of replication studies make it difficult to reach confident
      conclusions from the evidence.

PMID- 30291742
TI  - Exnovation of Low Value Care: A Decade of Prostate-Specific Antigen Screening
      Practices.
AB  - OBJECTIVES: To examine prostate-specific antigen (PSA) screening practice change
      in subgroups of men defined in guidelines and in various regions and to identify
      factors associated with change in screening practices. DESIGN: Observational
      study using serial cross-sections, 2003 to 2013. SETTING: National fee-for
      service Medicare. PARTICIPANTS: Men aged 68 and older eligible for prostate
      cancer screening. MEASUREMENTS: National PSA screening practices in men aged 68
      and older from 2003 to 2013 and change in regional screening rates in men aged 75
      and older. RESULTS: The PSA screening rate in men aged 68 and older was 17.2% in
      2003, 22.3% in 2008, and 18.6% in 2013 (p < .001 for all differences); rates
      ended slightly lower than rates in 2003 only in men 80 and older. Racial
      disparities in screening became less pronounced over this period. In men aged 75
      and older, change in regional screening rates varied widely, with absolute rates
      growing by 15 per 100 enrollees in some areas and declining by the same amount in
      others. Areas with high social capital, a measure associated with diffusion of
      new ideas, were more likely to decline; malpractice intensity and managed care
      penetration had no effect. CONCLUSION: Studying Medicare enrollees over time, we
      found little reduction in PSA screening and even increases according to race and
      in some regions. The heterogeneous changes across regions suggest that consistent
      reduction in the use of low-value care may require change strategies that go
      beyond evidence and guidelines to include monitoring and feedback on performance.

PMID- 30291743
TI  - Reduced Autobiographical Memory Specificity Among Maltreated Preschoolers: The
      Indirect Effect of Neglect Through Maternal Reminiscing.
AB  - Maternal reminiscing and preschoolers' (M = 5.00 years, SD = 1.11)
      autobiographical memory specificity (AMS) were examined among abusive (n = 24),
      neglecting (n = 78), emotionally maltreating (n = 32), and demographically
      similar nonmaltreating families (n = 74). Neglect was negatively associated with
      child AMS and the quantity of maternal elaborations. In a moderated mediation
      model, neglect was negatively associated with the quantity of maternal
      elaborations, which was positively associated with AMS when mothers reminisced in
      a coherent and sensitive manner (i.e., affective quality). In the context of high
      maternal affective quality, maternal elaborative quantity accounted for reduced
      AMS among neglected preschoolers. The findings extend observations of reduced AMS
      to neglected preschoolers and inform theoretical models of autobiographical
      memory development.

PMID- 30291744
TI  - Changes in health-related quality of life after discharge from an intensive care
      unit: a systematic review.
AB  - Quality of life after critical illness is becoming increasingly important as
      survival improves. Various measures have been used to study the quality of life
      of patients discharged from intensive care. We systematically reviewed validated
      measures of quality of life and their results. We searched PubMed, CENTRAL,
      CINAHL, Web of Science and Open Grey for studies of quality of life, measured
      after discharge from intensive care. We categorised studied populations as:
      general; restricted to level-3 care or critical care beyond 5 days; and septic
      patients. We included quality of life measured at any time after hospital
      discharge. We identified 48 studies. Thirty-one studies used the Medical Outcomes
      Study 36-Item Short Form Health Survey (SF-36) and 19 used the EuroQol-5D (EQ
      5D); eight used both and nine used alternative validated measures. Follow-up
      rates ranged from 26-100%. Quality of life after critical care was worse than for
      age- and sex-matched populations. Quality of life improved for one year after
      hospital discharge. The aspects of life that improved most were physical
      function, physical role, vitality and social function. However, these domains
      were also the least likely to recover to population norms as they were more
      profoundly affected by critical illness.

PMID- 30291745
TI  - Inhaler Technique Education and Exacerbation Risk in Older Adults with Asthma or
      Chronic Obstructive Pulmonary Disease: A Meta-Analysis.
AB  - OBJECTIVES: To evaluate the effect of inhaler education programs on clinical
      outcomes and exacerbation rates in older adults with asthma or chronic
      obstructive pulmonary disease (COPD). DESIGN: Systematic review and meta
      analysis. SETTING AND PARTICIPANTS: Older adults with asthma or COPD, either in
      primary or secondary health care and pharmacy setting. MEASUREMENTS: We searched
      the Medline, Embase, and Central databases according to the main eligibility
      criteria for inclusion: systematic reviews, meta-analysis, clinical trials and
      quasi-experimental studies; participants aged 65 and older; education on inhaler
      technique and reporting of disease control and exacerbation rates. We used the
      Grading of Recommendations, Assessment, Development and Evaluations scale for
      quality assessment and used a random-effect model with Mantel-Haenszel adjustment
      to perform a meta-analysis. RESULTS: We included 8 studies (4 randomized, 4 quasi
      experimental) with a total of 1,812 participants. The most frequent type of
      intervention was physical demonstration of inhaler technique, training with
      placebo devices. Five studies showed significant reduction in exacerbation rates
      (pooled risk ratio=0.71, 95% confidence interval=0.59-0.86; p < .001), although
      effect on disease control and quality of life showed high discrepancy in the
      reported results, and all randomized studies revealed uncertainty in their risk
      of bias assessment. CONCLUSION: All interventions seemed to improve inhaler
      performance and clinically relevant outcomes, but a placebo device could be the
      most effective. There is evidence that interventions reduce exacerbation risk in
      older adults, although to an overall moderate degree.

PMID- 30291746
TI  - Orthographic-Phonological Mapping and the Emergence of Visual Expertise for
      Print: A Developmental Event-Related Potential Study.
AB  - The N1 effect is an electrophysiological marker of visual specialization for
      print. The phonological mapping hypothesis (Maurer & McCandliss, 2007) posits
      that the left-lateralized effect reflects grapheme-phoneme integration. In this
      event-related potential study, first (age = 7.06 years, N = 32) and third-grade
      readers (age = 9.29 years, N = 28) were presented with pairs of pseudowords and
      Armenian character strings in a novel implicit same-different paradigm. To test
      the phonological mapping hypothesis, stimuli were presented in visual-only and
      audiovisual conditions. The results demonstrated that tuning for print already
      emerges in first grade. Moreover, the parallel presentation of auditory stimuli
      enhanced the N1 effect suggesting a role of orthographic-phonological mapping in
      the development of specialization for print.

PMID- 30291747
TI  - Trends in Polypharmacy in Japan: A Nationwide Retrospective Study.
AB  - OBJECTIVES: To describe and examine trends in polypharmacy according to age in
      Japan from 2010 to 2016. DESIGN: Retrospective observational study. SETTING:
      Outpatient settings. PARTICIPANTS: Japanese individuals aged 20 and older.
      MEASUREMENTS: We analyzed pharmacy claims data that the Japanese Ministry of
      Health, Labor, and Welfare provided in the Survey of Medical Care Activities in
      Public Health Insurance from 2010 to 2016. The use of 5 or more oral prescription
      medications per month was defined as polypharmacy and of 10 or more as excessive
      polypharmacy. Regression analysis was used to estimate trends in polypharmacy
      with annual percentage changes. Using number of medications (polypharmacy vs
      excessive polypharmacy), trends in polypharmacy and crude and age-adjusted rates
      of polypharmacy per 1,000 persons were calculated according to year and age group
      (20-34, 35-49, 50-64, 65-79, >= 80). RESULTS: We analyzed 240 million pharmacy
      claims data. The age-adjusted monthly prevalence rate of polypharmacy increased
      from 85.2 to 93.8 per 1,000 persons per month and of excessive polypharmacy from
      13.6 to 14.0 per 1,000 persons per month from 2010 to 2016 in the entire study
      population. The highest rate of polypharmacy (per 1,000 persons) was observed in
      2016 in those aged 80 and older (326.8), followed by those aged 65 to 79 (167.3).
      The polypharmacy rate increased by 6.3% (95% confidence interval (CI)=4.0-8.7)
      per year from 2010 to 2012, then decreased by 0.7% (95% CI=-1.3-0.0) per year
      from 2012 to 2016. The rate of excessive polypharmacy increased by 4.5% (95%
      CI=1.1-8.0) per year from 2010 to 2013 and then decreased by 3.7% (95% CI=-6.7 to
      -0.6) per year from 2013 to 2016. CONCLUSION: The overall trend of polypharmacy
      in Japan increased during the study period, although the increase ceased in 2013
      and then declined from 2013 to 2016. Policy changes in Japan might be responsible
      for some of the changes.

PMID- 30291748
TI  - Characteristics and Patterns of Marijuana Use in Community-Dwelling Older Adults.
AB  - OBJECTIVES: To understand patterns of marijuana use in community-dwelling older
      adults in Colorado. DESIGN: Anonymous survey. SETTING: Two academic geriatric
      primary care clinics. PARTICIPANTS: English-speaking individuals. MEASUREMENTS:
      We assessed self-reported characteristics and patterns of marijuana use and
      effect on targeted symptoms. Survey analysis focused on current users, defined as
      individuals who had used marijuana in the past 3 years. RESULTS: Three hundred
      forty-five individuals completed the survey (55% response rate); 113 (32%) had
      used marijuana in the past, of whom 55 (16%) had used since legalization. More
      than half of current users were aged 75 and older, and one-quarter were aged 85
      and older. Most current users were white women. Of current users, 44% used
      marijuana products at least weekly for common conditions including chronic pain,
      depression, anxiety, and insomnia, and most found marijuana helpful for these
      conditions. Most respondents reported obtaining marijuana recreationally (67%)
      without a prescription. Nine respondents reported negative side effects
      attributable to marijuana use. CONCLUSION: To our knowledge, this is the first
      study to characterize marijuana use of older adults in a state in which it is
      legal for medical and recreational use. Marijuana was used for several common
      geriatric conditions, and respondents reported few side effects. The small number
      of survey respondents, the lack of generalizability in states where marijuana
      sales are illegal, and participation bias were the main study limitations.
      Further research is needed to better understand useful or harmful effects in this
      population. J Am Geriatr Soc 66:2167-2171, 2018.

PMID- 30291749
TI  - The effect of network size and sampling completeness in depauperate networks.
AB  - The accurate estimation of interaction network structure is essential for
      understanding network stability and function. A growing number of studies
      evaluate under-sampling as the degree of sampling completeness (proportional
      richness observed). How the relationship between network structural metrics and
      sampling completeness varies across networks of different sizes remains unclear,
      but this relationship has implications for the within- and between-system
      comparability of network structure. Here, we test the combined effects of network
      size and sampling completeness on the structure of spatially distinct networks
      (i.e., subwebs) in a host-parasitoid model system to better understand the within
      system variability in metric bias. Richness estimates were used to quantify a
      gradient of sampling completeness of species and interactions across randomly
      subsampled subwebs. The combined impacts of network size and sampling
      completeness on the estimated values of twelve unweighted and weighted network
      metrics were tested. The robustness of network metrics to under-sampling was
      strongly related to network size, and sampling completeness of interactions were
      generally a better predictor of metric bias than sampling completeness of
      species. Weighted metrics often performed better than unweighted metrics at low
      sampling completeness; however, this was mainly evident at large rather than
      small subweb size. These outcomes highlight the significance of under-sampling
      for the comparability of both unweighted and weighted network metrics when
      networks are small and vary in size. This has implications for within-system
      comparability of species-poor networks and, more generally, reveals problems with
      under-sampling ecological networks that may otherwise be difficult to detect in
      species-rich networks. To mitigate the impacts of under-sampling, more careful
      considerations of system-specific variation in metric bias are needed.

PMID- 30291750
TI  - Alda-1, an aldehyde dehydrogenase-2 agonist, causes deterioration in renal
      functions following ischemia-reperfusion injury due to crystalline nephropathy.
AB  - Renal ischemia-reperfusion injury (IRI) induces the production of aldehydes which
      are detoxified by aldehyde dehydrogenases (ALDHs). Alda-1 is a selective ALDH2
      agonist and its protective effect was demonstrated in several conditions. The
      effect of Alda-1 on the kidney or on renal IRI was not investigated. We
      investigated the effect of Alda-1 on the renal dysfunction following IRI. Wistar
      rats underwent left IRI for 40 min. Group-Alda (n = 11) received Alda-1 starting
      24 h before IRI and continued for 7 days thereafter when renal functions were
      measured. Group-Vx (n = 11) underwent similar protocol but received the
      dissolvent. Alda-1 did not affect renal blood flow or glomerular filtration rate
      in the left ischemic kidney in Group-Alda compared to Group-Vx (3.05 +/- 0.50 vs.
      3.53 +/- 0.70, and 0.40 +/- 0.06 vs. 0.51 +/- 0.08, respectively, p > .05 for
      both). However, left renal fractional sodium excretion was higher in Group-Alda
      (2.80 +/- 0.43 vs. 1.37 +/- 0.36, p = .02). Alda-1 also adversely affected the
      gene expressions of kidney injury molecule-1 and neutrophil gelatinase-associated
      lipocalin (217 +/- 38 vs. 99 +/- 13 and 49 +/- 13 vs. 20 +/- 5, respectively, p <
      .05 for both) and the alterations in tumor necrosis factor-alpha, transforming
      growth factor-beta1, plasminogen activator inhibitor-1, fibronectin 1 and p53
      (4.4 +/- 0.9 vs. 2.1 +/- 0.3, 1.5 +/- 0.1 vs. 1.1 +/- 0.1, 30.0 +/- 2.7 vs. 11.7
      +/- 2.3, 3.6 +/- 0.4 vs. 2.1 +/- 0.2 and 1.3 +/- 0.1 vs. 0.9 +/- 0.07,
      respectively, p <= .05 for all). This was associated with intratubular crystal
      deposition suggestive of crystalline nephropathy. Alda-1 exacerbated the IRI
      induced renal tubular dysfunction and alterations in markers of acute kidney
      injury, biomarkers of inflammation, fibrosis and apoptosis and this was
      associated with intratubular crystal deposition suggestive of crystalline
      nephropathy.

PMID- 30291751
TI  - A multicomponent approach toward understanding emotion regulation in
      schizophrenia.
AB  - OBJECTIVES: Emotion deficits are well documented in people with schizophrenia.
      Far less is known about their ability to implement emotion regulation strategies.
      We sought to explore whether people with schizophrenia can modify their emotion
      responses similar to controls. METHODS: People with (n = 25) and without (n = 21)
      schizophrenia were instructed to amplify positive-emotion expression, reappraise
      negative emotion experience, and suppress physiological response. Multiple
      components of emotion response were measured (experience, expression, and
      physiology). RESULTS: Although people with schizophrenia showed increased
      positive expressivity following amplification and decreased negative emotion
      experience following reappraisal, overall, they expressed less positive emotion
      and experienced more negative emotion compared with controls. Neither group was
      effective at physiological suppression. CONCLUSIONS: Together these findings
      suggest that people with schizophrenia can engage in amplification and
      reappraisal when explicitly instructed to do so, albeit additional practice may
      be necessary to modify emotion responses to levels similar to controls.

PMID- 30291752
TI  - What's in a name? Patient registration errors and their threat to transfusion
      safety.

PMID- 30291753
TI  - Soluble CD40L and CD62P levels differ in single-donor apheresis platelet
      concentrates and buffy coat-derived pooled platelet concentrates.
AB  - BACKGROUND: Platelet storage lesions are structural and biochemical changes in
      platelet concentrates (PCs), and depend on variables in collection and
      processing, as well as secondary procedures and storage conditions; such lesions
      can be mitigated by the use of platelet additive solutions (PASs). STUDY DESIGN
      AND METHODS: This study investigated release of the inflammatory markers sCD40L
      and sCD62P by single-donor apheresis platelet concentrates (SDA-PCs) and buffy
      coat-derived pooled platelet concentrates (PPCs) before and after storage. SDA-PC
      and PPC samples (n = 9089) processed by various methods and stored for different
      durations were obtained following production in one regional setting, the French
      National Blood Service. Soluble factors were quantified in PC supernatants
      immediately after processing and at the time of delivery, using biological
      testing technology (Luminex). RESULTS: SDA-PCs appeared more activated than PPCs
      at the end of the production step (i.e., prior to storage); however,
      proinflammatory soluble factors exhibited greater increases in PPCs than in SDA
      PCs during storage. In SDA-PCs, PAS-D (65%) led to reduced secretion of sCD62P,
      but favored secretion of sCD40L, compared with the alternative PAS-E. CONCLUSION:
      These data stress the importance of the production (processing) steps of PC
      manufacture and of storage. The extent to which they affect patient outcomes
      awaits further investigation in clinical studies.

PMID- 30291754
TI  - Cascadia Rising: thoughts on a Seattle earthquake disaster exercise.
AB  - BACKGROUND: The Cascadia subduction zone off the US Pacific Northwest coast
      produces a Force 9 earthquake once every 300 years. Cascadia Rising was a
      regional disaster drill modeled on such an event. Western Washington State has 5
      million people and one Level I trauma center. STUDY DESIGN AND METHODS: The blood
      response of the trauma center and region were modeled under the conditions laid
      down in the disaster scenario. The scenario assumed structural damage to the 1931
      reinforced concrete building housing the trauma hospital transfusion service with
      loss of electricity, data services, and water. The regional blood center, in a
      newer building located six blocks away, suffered less disruption. The regional
      blood inventory is in a blood component manufacturing facility 18 miles south of
      downtown. RESULTS: At best and at risk to life, the trauma center could issue
      universally compatible components at a rate of 60 components/hr from a damaged
      but still accessible transfusion service. Usable inventory would be expended in 4
      hours with no clear mechanism and rules for resupply. The regional center has
      additional group O red blood cells and AB or A plasma to sustain that rate of
      usage for several more hours but no protocols for reestablishing communication or
      "push" resupply. Regional resources will be gone in less than a day. CONCLUSIONS:
      After a major Cascadia earthquake, blood resources may fail immediately, but even
      with luck, local resources used emergently at maximal issue rates will last 4 to
      14 hours.(c) 2018 AABB.

PMID- 30291755
TI  - Blood transfusions in preterm infants: changes on perfusion index and
      intermittent hypoxemia.
AB  - BACKGROUND: Red blood cell (RBC) transfusion decreases intermittent hypoxemia
      (IH) events beyond the first week of life. This benefit may be related to
      improved perfusion to the respiratory control network. Perfusion index (PI) is a
      perfusion measure provided by the pulse oximeter. We hypothesized that the
      benefit in IH after RBC transfusion is associated with an increase in PI. In
      addition, we assessed the value of PI and clinical measures in predicting the
      effect of RBC transfusion on IH. STUDY DESIGN AND METHODS: We prospectively
      enrolled infants less than 30 weeks' gestation age. PI and oxygen saturation
      (SpO2 ) were monitored with high-resolution pulse oximeters 24 hours before and
      after RBC transfusion. Data were analyzed at three postnatal periods: Epoch 1,
      first week of life (1 to 7 days of life); Epoch 2, 2 to 4 weeks of life (8 to 28
      days of life); and Epoch 3, 4 to 8 weeks of life. RESULTS: A total of 118
      transfusions were analyzed. IH measures significantly decreased after transfusion
      in Epochs 2 and 3. PI significantly increased after transfusion, but it did not
      correlate with the decrease in IH measures. Mechanical ventilation, fraction of
      inspired oxygen (FiO2 ), and IH measures influenced the effects on oxygenation.
      CONCLUSIONS: RBC transfusion improved IH after the first week of life. The
      benefit in IH did not correlate with PI increase after transfusion.
      Pretransfusion respiratory support and IH measures predicted the effect of
      transfusion on oxygenation.

PMID- 30291756
TI  - Comparison of administration of platelet concentrates suspended in M-sol or BRS-A
      for pediatric patients.
AB  - BACKGROUND: Two different platelet additive solutions (PASs), M-sol and BRS-A,
      used in succession, have been reported as novel PASs in Japan. However, there are
      not enough clinical data comparing platelet concentrates (PCs) suspended in these
      PASs. STUDY DESIGN AND METHODS: A retrospective cohort study of consecutive cases
      was performed between 2013 and 2018. For the first 30 months, children with
      primary hematologic and/or malignant diseases were transfused resuspended PCs in
      M-sol (RPC-M) as plasma-replaced PCs. For the subsequent 30 months, children were
      transfused plasma-replaced PCs in BRS-A (RPC-B) under the same conditions.
      Children transfused with conventional PCs (containing residual plasma) were
      defined as controls. We evaluated the frequency of adverse events, corrected
      count increment (CCI), and bleeding occurrence in the children. RESULTS: Overall,
      84 patients received 679 conventional PC transfusions. Allergic transfusion
      reactions (ATRs) occurred in 12 (14.3%) patients transfused with 12 (1.8%) bags.
      Fifty-nine patients received a total of 1182 bags of RPC-M, and one patient
      (1.7%) had five (0.4%) ATR episodes. During the last 30 months, 58 patients were
      transfused 1044 bags of RPC-B, with ATRs occurring in four (6.9%) patients
      transfused with four (0.4%) bags. No other adverse events were observed with
      either RPC-M or RPC-B. CCIs (24 hr) were not significantly different for the
      three different PCs, and posttransfusion bleeding was not observed. CONCLUSIONS:
      Plasma-replaced PC using two different PAS in children appeared to prevent ATRs
      accompanied without other adverse events in children. Transfusion efficacy was
      not significant; therefore, either of the PASs could be used with equivalent
      results based on the clinical situation.

PMID- 30291757
TI  - Early Crying, Sleeping, and Feeding Problems and Trajectories of Attention
      Problems From Childhood to Adulthood.
AB  - This study investigated if crying, sleeping or feeding problems that co-occur
      (multiple regulatory problems [RPs]) or are persistent predict attention problems
      and diagnoses of attention deficit hyperactivity disorder (ADHD) in childhood and
      adulthood. Participants were 342 individuals who were assessed at 5, 20, and 56
      months for crying, sleeping, and feeding (RPs) and at 6, 8, and 28 years for ADHD
      diagnoses, attention problems, and attention span. Infants/toddlers with
      multiple/persistent RPs had an increased risk of receiving an ADHD diagnosis both
      in childhood and adulthood compared to those who never had RPs.
      Multiple/persistent RPs were further associated with a high-decreasing attention
      problems trajectory from childhood to adulthood. Interventions to alleviate early
      RPs may prevent the development of attention problems.

PMID- 30291758
TI  - Repeat whole blood donors with a ferritin level of 30 MUg/L or less show
      functional iron depletion.
AB  - BACKGROUND: Whole blood donors are screened for iron depletion through hemoglobin
      measurement alone or in combination with ferritin. Ferritin measurement gives the
      advantage of earlier detection of iron depletion. In a previous study we
      identified a ferritin level of 30 MUg/L or less as a possible indicator of
      suboptimal erythropoiesis. In this study, erythropoietic parameters were measured
      to determine if a ferritin level of 30 MUg/L or less is indicative of iron
      deficient erythropoiesis in repeat whole blood donors. STUDY DESIGN AND METHODS:
      Twenty-one healthy male repeat whole blood donors were divided into two groups
      according to their predonation ferritin values: 30 MUg/L or less (low-ferritin
      group) and greater than 30 MUg/L (normal-ferritin group). Ferritin and
      erythropoietic parameters were measured before whole blood donation and weekly in
      the 8 weeks after donation. RESULTS: A significantly lower value was found for
      hemoglobin, mean corpuscular volume (MCV), reticulocytes, and reticulocyte
      hemoglobin content on at least three of the nine time points in the low-ferritin
      group compared to the normal-ferritin group (p < 0.05). Of these parameters, MCV
      and reticulocyte hemoglobin content were significantly lower before donation as
      well as during all 8 weeks following donation (p < 0.05). CONCLUSION: Based on
      the lower values of the erythropoietic parameters in the low-ferritin group, it
      can be concluded that repeat whole blood donors with a ferritin value of 30 MUg/L
      or less have iron-deficient erythropoiesis and therefore require a longer
      donation interval than the current 56 days.

PMID- 30291759
TI  - Whole genome sequencing reveals rare off-target mutations and considerable
      inherent genetic or/and somaclonal variations in CRISPR/Cas9-edited cotton
      plants.
AB  - The CRISPR/Cas9 system has been extensively applied for crop improvement.
      However, our understanding of Cas9 specificity is very limited in Cas9-edited
      plants. To identify on- and off-target mutation in an edited crop, we described
      whole genome sequencing (WGS) of 14 Cas9-edited cotton plants targeted to three
      genes, and three negative (Ne) control and three wild-type (WT) plants. In total,
      4188-6404 unique single-nucleotide polymorphisms (SNPs) and 312-745
      insertions/deletions (indels) were detected in 14 Cas9-edited plants compared to
      WT, negative and cotton reference genome sequences. Since the majority of these
      variations lack a protospacer-adjacent motif (PAM), we demonstrated that the most
      variations following Cas9-edited are due either to somaclonal variation or/and
      pre-existing/inherent variation from maternal plants, but not off-target effects.
      Of a total of 4413 potential off-target sites (allowing <=5 mismatches within the
      20-bp sgRNA and 3-bp PAM sequences), the WGS data revealed that only four are
      bona fide off-target indel mutations, validated by Sanger sequencing. Moreover,
      inherent genetic variation of WT can generate novel off-target sites and destroy
      PAMs, which suggested great care should be taken to design sgRNA for the
      minimizing of off-target effect. These findings suggested that CRISPR/Cas9 system
      is highly specific for cotton plants.

PMID- 30291760
TI  - Impact of household composition and family functioning on health of Hispanic
      mothers in mental health treatment: A secondary analysis study.
AB  - WHAT IS KNOWN ON THE SUBJECT?: Mothers with mental health problems are at risk of
      well-being and experience lack of support. There is little research focusing on
      the effect of household composition on health of Hispanic mothers with mental
      illness. As the family is a central feature in Hispanic lives and there is a high
      dependence on the family for help, it is crucial to understand how household
      composition and family functioning influences Hispanic mothers' health and well
      being. WHAT DOES THE PAPER ADDS TO EXISTING KNOWLEDGE?: Living with at least one
      other adult in the household are related to better Hispanic mothers' physical and
      psychological health. Mothers living with a greater number of adult in the house
      are more likely to have fatigue and depression. More family hassles are
      associated with worse health outcomes in Hispanic mothers with mental health
      problems WHAT ARE THE IMPLICATIONS FOR PRACTICE?: There is a need to assess
      family members who are supportive to Hispanic mothers and to address families'
      basic needs in the intervention. Interventions for Hispanic mothers with mental
      health problems should be grounded in supporting the strengths of the Hispanic
      familial networks. A family-centred approach for mothers with mental health
      problems requires integrated assessments and interventions including the families
      as units. ABSTRACT: Introduction Household composition is seen as a critical
      factor for recovery of Hispanic mothers with mental illness, but little research
      has examined the relationship of household composition and health. Aim This study
      examined how household composition and family functioning impact on both physical
      and psychological health of Hispanic mothers receiving outpatient mental health
      services. Method The study analysed baseline data of 137 Hispanic mothers
      participating in a randomized trial of "Healthy Home," a family-strengthening
      home health intervention. A bilingual (English/Spanish) research assessor
      interviewed participants regarding household composition, family hassles, family
      cohesion and mother's physical and psychological health. Results Mothers living
      with at least one other adult and having fewer family hassles had better health
      outcomes. Mothers living with a greater number of adult in the house were more
      likely to have fatigue and depression. Discussion Hispanic mothers having no
      adults to help them in the house are less able to maintain their physical and
      psychological health. A family-centred approach for mothers requires integrated
      assessments and interventions including the families as units. Implication for
      practice Interventions for Hispanic mothers with mental health problems should be
      grounded in supporting the values and strengths of the Hispanic familial
      networks.

PMID- 30291761
TI  - The psychometric properties of the Collaborative Assessment and Management of
      Suicidality rating scale.
AB  - OBJECTIVE: The CAMS Rating Scale (CRS) is an adherence measure for the
      Collaborative Assessment and Management of Suicidality (CAMS), a suicide-specific
      clinical intervention. This study examined the ability of the CRS to assess
      adherence to CAMS. METHODS: Video-recorded therapy sessions of clinicians
      delivering either CAMS or Enhanced Care-As-Usual (E-CAU) were rated with the CRS.
      These ratings (N = 98) were used to evaluate criterion validity, internal
      consistency, and factor structure. RESULTS: Criterion validity and factor
      analyses did not support the organization of the CRS into its current subscales.
      Furthermore, the identified factor model and item-level statistics revealed weak
      CRS items. Finally, internal consistency was higher among CAMS clinicians than
      among clinicians delivering E-CAU. CONCLUSION: These results establish the CRS as
      a measure that can effectively assess the adherence to CAMS in its current form.
      Potential revisions to future iterations of the CRS are discussed.

PMID- 30291762
TI  - Complications of a severe autoimmune hemolytic anemia crisis: transfusional iron
      overload and gangrenous cholecystitis.
AB  - BACKGROUND: Evans syndrome is a rare autoimmune disorder that is defined by the
      simultaneous or sequential presence of two or more cytopenias without an obvious
      underlying precipitating cause. Evans syndrome usually follows a chronic
      relapsing and remitting course and is quite rare, making it difficult to evaluate
      in clinical studies. CASE REPORT: A 66-year-old male patient with a 17-year
      history of Evans syndrome presented with fulminant autoimmune hemolytic anemia
      (AIHA). He presented with a markedly elevated C-reactive protein (CRP; 46 mg/L
      [normal, 0-5 mg/L]) before onset of a decrease in hemoglobin. He required the
      transfusion of 20 units of red blood cells while awaiting response to aggressive
      immunosuppressive therapy including high-dose corticosteroids, intravenous
      immunoglobin therapy, and rituximab. He achieved a complete hematologic response.
      RESULTS: His postdischarge course was complicated by acute cholecystitis
      requiring laparoscopic cholecystectomy. In addition, his transfusional iron
      overload requiring 16 phlebotomies to reduce his ferritin level from 4933 MUg/L
      to 326 MUg/L, with phlebotomies ongoing every 2 weeks to achieve a ferritin level
      of less than 100 MUg/L. CONCLUSION: Neither transfusional iron overload nor acute
      cholecystitis are well-recognized complications of a severe episode of AIHA. An
      elevated CRP has been recently recognized as an important prognostic marker in
      patients with immune thrombocytopenic purpura and this case suggests a need to
      evaluate its utility in AIHA.

PMID- 30291763
TI  - Electronic nicotine delivery system (ENDS) use in relation to mental health
      conditions, past-month serious psychological distress and cigarette smoking
      status, 2017.
AB  - BACKGROUND AND AIMS: Adults with mental health conditions (MHC) exhibit
      disproportionately high smoking prevalence and experience profound tobacco
      related disparities. US nationally representative surveys from 2012 to 2015 found
      relatively high usage of electronic nicotine delivery systems (ENDS; e.g. e
      cigarettes) among adults with MHC. However, research has not examined these
      associations specifically among never smokers. Aims were to examine associations
      among MHC diagnosis, serious psychological distress (SPD) and ENDS use and to
      test whether associations varied by cigarette smoking status. DESIGN: Cross
      sectional US nationally representative survey. SETTING: United States, 2017.
      PARTICIPANTS: A total of 5762 adults (52.0% female; 64.8% non-Hispanic white,
      11.4% non-Hispanic black, 15.9% Hispanic, 7.9% non-Hispanic other). MEASUREMENTS:
      Outcomes were lifetime, current and current daily ENDS use. Predictors were
      lifetime MHC, past-month SPD and cigarette smoking status, and covariates were
      gender, age, race/ethnicity, education and annual household income. FINDINGS:
      lifetime MHC and past-month SPD were each associated with higher likelihood of
      having ever used ENDS (P <= 0.001), currently using ENDS (P <= 0.001) and
      currently using ENDS daily (P < 0.05). There were interactions between MHC and
      smoking status in predicting ENDS use, such that MHC status predicted higher
      lifetime and current ENDS use specifically among never and current smokers. Never
      smokers with MHC had 2.62 higher odds [95% confidence interval, (CI) = 1.54,
      4.45] of current ENDS use than those without MHC. Among never smokers, those with
      MHC indicated higher expectations that ENDS would improve relaxation and
      concentration (P < 0.05). CONCLUSIONS: In 2017, US adults with versus without
      mental health conditions (MHC) were more likely to use electronic nicotine
      delivery systems (ENDS). In particular, both never and current smokers with MHC
      reported disproportionately high rates of current ENDS use.

PMID- 30291764
TI  - Amygdala subnuclei and healthy cognitive aging.
AB  - Amygdala is a group of nuclei involved in the neural circuits of fear, reward
      learning, and stress. The main goal of this magnetic resonance imaging (MRI)
      study was to investigate the relationship between age and the amygdala subnuclei
      volumes in a large cohort of healthy individuals. Our second goal was to
      determine effects of the apolipoprotein E (APOE) and brain-derived neurotrophic
      factor (BDNF) polymorphisms on the amygdala structure. One hundred and twenty-six
      healthy participants (18-85 years old) were recruited for this study. MRI
      datasets were acquired on a 4.7 T system. Amygdala was manually segmented into
      five major subdivisions (lateral, basal, accessory basal nuclei, and cortical,
      and centromedial groups). The BDNF (methionine and homozygous valine) and APOE
      genotypes (epsilon2, homozygous epsilon3, and epsilon4) were obtained using
      single nucleotide polymorphisms. We found significant nonlinear negative
      associations between age and the total amygdala and its lateral, basal, and
      accessory basal nuclei volumes, while the cortical amygdala showed a trend. These
      age-related associations were found only in males but not in females.
      Centromedial amygdala did not show any relationship with age. We did not observe
      any statistically significant effects of APOE and BDNF polymorphisms on the
      amygdala subnuclei volumes. In contrast to APOE epsilon2 allele carriers, both
      older APOE epsilon4 and epsilon3 allele carriers had smaller lateral, basal,
      accessory basal nuclei volumes compared to their younger counterparts. This study
      indicates that amygdala subnuclei might be nonuniformly affected by aging and
      that age-related association might be gender specific.

PMID- 30291766
TI  - Mini photopheresis for refractory chronic graft-versus-host disease in children
      and adolescents.
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) has been established to treat
      graft-versus-host disease. Our mini ECP technique (mini-ECP) allows for treatment
      of patients with GVHD and contraindications for classical ECP or low body weight.
      The safety and efficacy of applying ECP for the long-term treatment of chronic
      GVHD (cGVHD) have not been described. STUDY DESIGN AND METHODS: A retrospective
      analysis of mini-ECP treatments for children and adolescents with cGVHD was
      performed. Mini-ECP with 100 to 200 mL of whole blood was used to treat 14
      patients. The median age at the start of treatment was 7 years (range, 1-17
      years), and median body weight was 20 kg (range, 8-53 kg). A total of 703 mini
      ECP treatments was performed. The median number of treatments per patient was 35
      (range, 8-129), and median treatment duration was 11 months (range, 1.4-28.5
      months). RESULTS: Mini-ECP was well tolerated. Four adverse events occurred in
      three patients, and two of them were related to the ECP procedure. Complete or
      partial responses were observed in 10 patients. Steroids were discontinued in
      seven patients and tapered in three others. Responses were seen in the skin,
      mouth, gastrointestinal tract, and eyes. CONCLUSION: Mini-ECP represents a less
      invasive ECP alternative for low-body-weight patients with cGVHD and
      contraindications for apheresis.

PMID- 30291767
TI  - In-house chemical library repurposing: A case example for Pseudomonas aeruginosa
      antibiofilm activity and quorum sensing inhibition.
AB  - Drug repurposing has become a recent trend in drug development programs, where
      previously developed drugs are explored for hit and redeveloped into potential
      therapeutic agents for new diseases. Globally, in any drug development program, a
      series of molecules are synthesized and evaluated for the hypothesized activity.
      Hits are developed into lead molecules or drugs, whereas the negative ones are
      shelved in the lab with no immediate use. We in this project took the previously
      sidelined small chemical molecules to the next level of utility, where previously
      developed in-house small molecules library are tested for the unexplored
      biological relevant activity. As biofilm formation and quorum sensing play a
      vital role in bacterial pathogenesis, we believe that they could be one of the
      most effective targets for antimicrobial agents. In this study, we report the
      evaluation of 50 different compounds for anti-biofilm and anti-quorum sensing
      activity against Pseudomonas aeruginosa. Out of the screened compounds, three
      hydrazine-carboxamide hybrid derivatives showed promising anti-biofilm property
      and inhibition of pyocyanin production without any direct antimicrobial activity
      and cytotoxicity issues. Hydrazine-carboxamide hybrids can be a new class and
      promising leads for further anti-biofilm and anti-virulence development against
      microbial infections.

PMID- 30291765
TI  - International neuromonitoring study group guidelines 2018: Part II: Optimal
      recurrent laryngeal nerve management for invasive thyroid cancer-incorporation of
      surgical, laryngeal, and neural electrophysiologic data.
AB  - The purpose of this publication was to inform surgeons as to the modern state-of
      the-art evidence-based guidelines for management of the recurrent laryngeal nerve
      invaded by malignancy through blending the domains of 1) surgical intraoperative
      information, 2) preoperative glottic function, and 3) intraoperative real-time
      electrophysiologic information. These guidelines generated by the International
      Neural Monitoring Study Group (INMSG) are envisioned to assist the clinical
      decision-making process involved in recurrent laryngeal nerve management during
      thyroid surgery by incorporating the important information domains of not only
      gross surgical findings but also intraoperative recurrent laryngeal nerve
      functional status and preoperative laryngoscopy findings. These guidelines are
      presented mainly through algorithmic workflow diagrams for convenience and the
      ease of application. These guidelines are published in conjunction with the INMSG
      Guidelines Part I: Staging Bilateral Thyroid Surgery With Monitoring Loss of
      Signal. Level of Evidence: 5 Laryngoscope, 128:S18-S27, 2018.

PMID- 30291769
TI  - Fatal Avian Influenza A/H5N1 Infection in a 36-Week Pregnant Woman Survived by
      her Newborn - Soc Trang, Vietnam, 2012.
AB  - Outbreaks of H5N1 Avian Influenza (AI) emerged in Indonesia, Thailand and Viet
      Nam during 2003- 2005. Its severe impact has been reported; the Food and
      Agriculture Organization (FAO) and World Bank (WB) estimated that Viet Nam lost
      up to 1.8% of GDP (1). Since then the country reported over 3000 H5N1 poultry
      outbreaks (2) and 127 human H5N1 cases and 64 dead. This article is protected by
      copyright. All rights reserved.

PMID- 30291768
TI  - Learning curve and surgical factors influencing the surgical outcomes during the
      initial experience with laparoscopic pancreaticoduodenectomy.
AB  - BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) requires sufficient
      laparoscopic training for optimal outcomes. Our aim is to determine the learning
      curve and investigate the factors influencing surgical outcomes during the
      learning curve. METHODS: We analyzed surgical results of 150 consecutive cases of
      LPD performed by three hepatopancreatobiliary surgeons during their 50 first
      cases. Learning curves were constructed by cumulative sum (CUSUM) analysis.
      Preoperative factors influencing resection time and blood loss were investigated
      in the introductory and stable periods. RESULTS : The learning curve could be
      divided into three phases: initial (1-20 cases), plateau (21-30), and stable (31
      50). Resection time with lymph node dissection was significantly longer during
      the introductory period (initial and plateau periods) (P < 0.01) but not the
      stable phase (P = 0.51). Multivariate analysis revealed that patients with
      pancreatitis had longer resection times and massive blood loss in both the
      introductory and stable periods (stable phase). High visceral fat area was also
      significantly related to massive blood loss in the introductory period (P =
      0.04). CONCLUSIONS: Hepatopancreatobiliary surgeons need more than 30 cases until
      LPD becomes stable. Lymph node dissection and patients with high visceral fat
      area and concomitant pancreatitis should be avoided during the introductory
      period of the learning curve.

PMID- 30291770
TI  - Prepubertal exposure to low doses of sodium arsenite impairs spermatogenesis and
      epididymal histophysiology in rats.
AB  - For the first time, juvenile toxicity of inorganic arsenic (As) was investigated
      in male rats, focusing on reproductive effects. As is a metalloid naturally
      occurring in the environment, being the inorganic forms the most toxics.
      Contaminated drinking water and agricultural products are the main prospectors of
      intoxication for general population. In the present study, Wistar male rats (21
      days old) were distributed into three groups (n = 10/group): control (received
      vehicle-filtered drinking water), As1 (received AsNaO2 at 0.01 mg L-1 ) and As2
      (received AsNaO2 at 10 mg L-1 ). The animals were euthanized on PND 53.
      Testicular damages increased in As1 and As2 compared to control (ie, presence of
      vacuolization, acidophilic cells, and epithelium degeneration). Testicular
      interstitium of As1 and As2 presented fluid's increase and intense inflammatory
      infiltration. In the epididymis there was reduction of sperm amount in the lumen,
      besides epithelium areas presenting cribriform aspect in As1 and As2, exfoliation
      of cells in the light (in As1) and vacuoles (in As2). In epididymis interstitium,
      inflammatory infiltrates were observed in initial segment of As1 and As2. AsNaO2
      changed immunolabeling pattern for androgen receptor in epididymis of As2,
      although serum testosterone levels was statistically comparable to control. Mass
      spectrometry revealed higher As concentrations in testis and epididymis of As2
      compared to As1 and Control. These results indicate compromise of spermatogenesis
      and epididymal histophysiology in AsNaO2 -treated animals, possibly impairing
      sperm quality and fertility in long-term, even at low levels of exposure.
      Investigations about the reversibility of reproductive damages are necessary to
      better understand the mechanisms of As reproductive toxicity.

PMID- 30291771
TI  - [Effect of High Hydrostatic Pressure Combined with Temperature on the
      Antigenicity and Conformation of Tropomyosin Purified from Shrimp].
AB  - Foodborne shrimp allergy events have occurred in recent years. To illustrate the
      mechanism of high hydrostatic pressure technology to change the allergenicity of
      shrimp, the major allergen tropomyosin was separated and purified from
      Litopenaeus vannamei, and indentified with matrix assisted laser desorption
      ionization time of flight mass spectrometry (MALDI-TOF-MS). The effect of
      temperature factor under high hydrostatic pressure was measured with indirect
      ELISA method, CD and fluorescence spectrum. The results showed that the
      antigenicity of TM protein had an increase after being heated at 35 or 45 C when
      treated at 300 MPa for 15 minutes, while the antigenicity decreased at 55, 65,
      and 75 C. With the increase of heat temperature, the secondary structure of TM
      also changed. The mutual transformation happened between the alpha-helix and beta
      sheet, beta-turn, and the random coil. The tertiary structure of TM was observed
      dynamic changes from the extended state to the folded state, and then re-extended
      state to re-folded state. These results suggested that high hydrostatic pressure
      combined with temperature could influence the antigenicity of TM by the change of
      conformation which would be useful as theoretical guidance on developing new
      methods or technologies for producing hypoallergenic shrimp products.

PMID- 30291772
TI  - [Experimental Study of the Diffusion Process of Pulsed-GMAW Plasma with Optical
      Emission Spectrometry].
AB  - In case of GMAW-P application, the product quality is strongly dependent on the
      arc plasma performances. Therefore, in order to improve the application, it is
      important to understand and characterize the fundamental plasma properties. In
      this paper, different techniques (high speed camera ,optical emission
      spectroscopy system, electrical data acquisition system, synchronous triggering
      device) were used to characterize the arc characteristic. The metal diffusion
      process from the peak time to the base time is discussed, as well as its physical
      characteristics. The results show that, in the peak time phase, a high
      concentration of metal vapor arc is concentrated in the plasma center of the
      range of about 1 mm, during the transition from the peak to the base pulse
      periods, the diffusion leads to an iron vapor flux from regions in the arc core
      to the arc fringes. The iron mol fraction of the peak time was up to 75%, only
      taking up 35% of the base time.

PMID- 30291773
TI  - [Research on Measurement Method of Gas Velocity Combined Absorption Spectroscopy
      Technique and Cross-Correlation].
AB  - For the small frequency shift and large error of tunable diode laser absorption
      spectroscopy (TDLAS) velocity method based on Doppler Effect in measuring the gas
      velocity, velocity measurement method combined fixed wavelength absorption
      spectroscopy and cross correlation is proposed in this paper. Considering the
      characteristics of the hydrocarbon fuel combustion products, 7 158.597 cm(- 1)
      absorption line of H(2)O molecular was selected. Through arranging two beams of
      fixed wavelength absorption measurement point of upstream and downstream, the gas
      velocity can be calculated by analyzing the cross-correlation properties of the
      two signals. The flat flame burner experiment system was used in the experimental
      research of the velocity measurement. The change of gas velocity with time under
      variable working condition was obtained. Under the same condition, numerical
      calculation is carried out. And the measurement results are compared with the
      results of the numerical simulation with relative deviation less than 8%. Then
      the method is preliminarily applied to measure the high speed plume of the
      kerosene-fueled Rocket Based Combined Cycle (RBCC) engine, and the upstream and
      downstream fluctuant signals of detectors were obtained. The velocity of the
      plume was calculated with cross correlation analysis which verifies the
      feasibility of this method. The experimental results show that the gas velocity
      measurement method has a wide measuring range with high measuring accuracy and
      little environment interference. The method proposed in this paper provides a
      simple and reliable method for the measurement of engine gas velocity.

PMID- 30291774
TI  - [Analysis of Flame Spectrum at the Initial Stage of 0 # Diesel Oil Combustion].
AB  - With small-scale oil pool experimental and spectral analysis method, the flame
      spectrum in initial stage of 0(#) diesel oil combustion was conducted a
      preliminary study for the first time, which was used to develop the technique of
      intelligent identification and suppression of fire extinguishing at the initial
      stage of diesel oil combustion. It educed the overall characteristics flame
      spectrum at the initial stage of 0(#) diesel oil combustion: in 200~380 nm
      wavelength of near-ultraviolet bands, the spectral intensity is the weakest, the
      spectral intensity does not change with wavelength, the number of characteristics
      spectral bands is minimum, the number of obvious characteristics spectral peaks
      is almost none; in 380~780 nm wavelength of visible bands, the spectral intensity
      is the strongest, the spectral intensity increases with wavelength, the number of
      characteristics spectral bands is maximum, the number of obvious characteristics
      spectral peaks is large; in 780~1 100 nm wavelength of near-infrared bands, the
      spectral intensity is relatively strong, the inflection point of spectral
      intensity appears in 780 nm, the appeared intensity decreases with wavelength,
      the number of characteristics spectral bands is relatively large, the number of
      obvious characteristics spectral peaks is at a certain number. It is educed
      through further analysis of the flame spectrum that: the primary intermediate
      radicals includes OH, CN, CH, C(2), H(2)O, etc; the primary characteristic
      spectral bands includes the OH racial bands of 3 064 ? System and Vibration
      Rotation bands, the CN racial bands of Violet System and Red System, the CH
      racial bands of 4 315 ? System, the C2 racial bands of The Swan system and
      Phillips Near Infra-red System, the H(2)O molecular Vibration-Rotation bands,
      etc; the bands and time distribution of primary intermediate radicals and its
      main generation mechanism; the existence of potassium in this experimental
      batches of 0(#) diesel oil and the spectral peak of spectral lines in 766 and 769
      nm is obvious; the peak of spectral intensity in 431, 512, 516, 547, 589, 766,
      769, 891, 927 nm is obvious, and it suitable for the sign of flame identification
      at the initial stage of 0(#) diesel oil combustion.

PMID- 30291775
TI  - [Spectroscopic Studies on the Host Plant Selection Mechanism of Trabala vishnou
      gigantina Yang (Lepidoptera: Lasiocampidae)].
AB  - Trabala vishnou gigantina Yang (Lepidoptera: Lasiocampidae) is a polyphagous
      forestry pest whose periodic breaking out results in great economic damage
      including total crop failure to forestry and fruit production in China. In this
      study, in order to improve the understanding of the host plant selection
      mechanism of T. vishnou gigantina larvae, locust, caragana, willow, poplar,
      apricot and sea-buckthorn were used as potential host plants for the test. Two
      way choice experiment method was used to study the T. vishnou gigantina Yang
      feeding preferences of the six kinds of plants. Moreover, the chemical component
      and physical structure of six plants were analyzed with Fourier transform
      infrared (FTIR) spectroscopy and X-ray diffraction (XRD). Among the six plants,
      T. vishnou gigantina larvae showed a strong preference for sea-buckthorn,
      followed by, apricot, willow, poplar, locust, and caragana. The FTIR analysis
      displayed that those six plants presented similar characteristic on absorption
      peak position, peak amount, and shape. The targets (1 154/1 733, 1 154/898) by
      FTIR showed that lipids and polysaccharide were major nutriments to affect the
      host plant selection of T. vishnou gigantina larvae. The XRD results showed that
      crystallinity index (CrI) also could affect the host plant selection of T.
      vishnou gigantina larvae. In this research, spectroscopy technology was firstly
      applied to the study of interactive relationship between insect and host, which
      would blaze a trail for intensive study of host plant selection mechanism of
      insect at molecular level.

PMID- 30291776
TI  - [The Study on Combined Screening Method for TBS and Cervical Cancer Cell's DNA
      Quantitative Analysis Based on Multi-Spectral Imaging Technology].
AB  - The traditional screening method of cervical cancer mainly involves TBS
      classification method and quantitative analysis method based on DNA, TBS
      screening method which has high diagnostic rate, but it needs experienced doctors
      to participate in the process with low sensitivity. Therefore, it is difficult to
      achieve early cervical cancer screening; cell's DNA quantitative analysis, only
      stained the nucleus, achieving a quantitative and automated analysis. Even with
      high sensitivity, the specificity is poor. So it is extremely necessary to
      realize the combination of screening for TBS and cell's DNA quantitative
      analysis, but the current TBS and DNA quantitative analysis combined screening
      method for the use of two different cell smear, time-consuming, laborious and
      very inconvenient, there is no screening method for cervical cancer on a
      combination of TBS and DNA quantitative analysis at home and abroad. This paper
      presents a method using TBS classification and DNA quantitative analysis on the
      same cell smear which was stained with Pap and Feulgen in order to solve the
      problem of the interference of the absorbance of DNA substance caused by multiple
      staining. a set of multi spectral imaging system and DNA absorbance peeling model
      are established based on linear multiple regression. With model solution, the
      real absorbance of the substance DNA was calculated, and the quantitative
      analysis of DNA was carried out. A pseudo color image is synthesized from 3 -
      band cell images with the close wavelength of RGB for TBS classification, so the
      organic combination of TBS and cell's DNA quantitative analysis is realized.
      Experiments show that the DNA quantitative analysis model of this method is
      stable, with small error and high diagnostic rate due to the fact that the pseudo
      color images used for TBS screening were bright, clear, and clear cytoplasm.
      Therefore, this method is very useful in the diagnosis and screening of cervical
      cancer.

PMID- 30291777
TI  - [Rapid Diagnosis of Sound, Yellow and Citrus Greening Leaves with Hyperspectral
      Imaging].
AB  - The feasibility was investigated for identifying sound, yellow and citrus
      greening leaves of navel orange trees based on hyperspectral imaging combined
      with correlation analysis and discriminant partial least square (DPLS) methods.
      The hyperspectral data of sound, yellow and citrus greening leaves were recorded
      in the wavelength range of 374.28~1 016.89 nm. Two regions of interest (ROI) were
      marked symmetrically on both sides along main veins with an ellipse of major axis
      of 60 pixels and minor axis of 30 pixels. The average reflectance spectrum was
      extracted from ROI regions. A pair wavelengths of 502.79 and 374.28 nm were
      chosen with correlation analysis method in the wavelength range of 374.28~1
      016.89 nm. The classification model was developed with the peak ratio of the pair
      wavelengths. This model was effective to sound leaves with the recognition
      accuracy of 1.7% but yellow and citrus greening leaves. The DPLS model was
      employed with the preprocessing spectra of second derivative and Savitzky-Golay
      smoothing. The recognition accuracy of this model was 100% for citrus greening
      leaves and yellow ones. The number of latent variables (LVs) was optimized with
      the leave one out cross validation method. The optimal LVs, correlation
      coefficient and standard error of calibration of the DPLS model were 17, 0.96 and
      0.13, respectively. The correction classification rate of the DPLS model was 100%
      for yellow leaves and citrus greening ones. Two-step method of the peak ratio
      models combination with the DPLS was proposed for identifying sound, yellow and
      citrus greening leaves. The new samples were applied to evaluation the
      classification ability of the two-step method, which included sound leaves of 10,
      citrus greening leaves of 10 and yellow leaves of 10. The correction
      classification rate reached 96.7%. Experimental results showed that it was
      feasible to identify sound, yellow and citrus greening leaves by hyperspectral
      imaging coupled with the peak ratio and DPLS models.

PMID- 30291778
TI  - Molecular mechanisms of non-thermal plasma-induced effects in cancer cells.
AB  - Plasma is the fourth state of matter with higher energy than gas; non-thermal
      plasma (NTP) is currently available. As NTP is useful in sterilization, promoting
      wound healing and cancer treatments, the molecular mechanisms of plasma-induced
      effects in living cells and microorganisms are of significant interest in plasma
      medicine with medical-engineering collaboration. Molecular mechanisms of plasma
      induced effects in cancer cells will be described in this minireview. Both direct
      and indirect methods to treat cancer cells with NTP have been developed. NTP
      interacts directly with not only cancer cells but also the liquids surrounding
      cancer cells and the immune cells that target them. Reactive oxygen and nitrogen
      species play key roles in NTP-induced effects; however, other mechanisms have
      been suggested. The complex interactions between NTP, cells and liquids have been
      extensively studied. In the future, details regarding NTP-induced effects on gene
      regulatory networks, signaling networks, and metabolic networks will be
      elucidated.

PMID- 30291779
TI  - Microbial transglutaminase for biotechnological and biomedical engineering.
AB  - Research on bacterial transglutaminase dates back to 1989, when the enzyme has
      been isolated from Streptomyces mobaraensis. Initially discovered during an
      extensive screening campaign to reduce costs in food manufacturing, it quickly
      appeared as a robust and versatile tool for biotechnological and pharmaceutical
      applications due to its excellent activity and simple handling. While pioneering
      attempts to make use of its extraordinary cross-linking ability resulted in
      heterogeneous polymers, currently it is applied to site-specifically ligate
      diverse biomolecules yielding precisely modified hybrid constructs comprising two
      or more components. This review covers the extensive and rapidly growing field of
      microbial transglutaminase-mediated bioconjugation with the focus on
      pharmaceutical research. In addition, engineering of the enzyme by directed
      evolution and rational design is highlighted. Moreover, cumbersome drawbacks of
      this technique mainly caused by the enzyme's substrate indiscrimination are
      discussed as well as the ways to bypass these limitations.

PMID- 30291780
TI  - FAM134B promotes adipogenesis by increasing vesicular activity in porcine and 3T3
      L1 adipocytes.
AB  - Family with sequence similarity 134, Member B (FAM134B), is a cis-Golgi
      transmembrane protein that is known to be necessary for the long-term survival of
      nociceptive and autonomic ganglion neurons. Recent work has shown that FAM134B
      plays a pivotal role in autophagy-mediated turnover of endoplasmic reticulum (ER)
      membranes, tumor inhibition and lipid homeostasis. In this study, we provide
      mechanistic links between FAM134B and ARF-related protein 1 (ARFRP1) and further
      show that FAM134B resides in the Golgi apparatus. Here, we found that FAM134B
      increased lipid accumulation in adipocytes. Transport vehicle number and ADP
      ribosylation factor (ARF) family gene expression were also increased by FAM134B
      overexpression, suggesting that vesicular transport activity enhanced lipid
      accumulation. ARF-related protein 1 (ARFRP1) is a GTPase that promotes protein
      trafficking. We show that FAM134B regulates the expression of ARFRP1, and the
      knockdown of ARFRP1 abolishes enhancement on lipid accumulation caused by
      FAM134B. In addition, FAM134B upregulates the PAT family protein (PAT), which
      associates with the lipid droplets (LDs) surface and promotes lipolysis by
      recruiting adipocyte triglyceride lipase (ATGL). These findings indicate that
      FAM134B promotes lipid accumulation and adipogenic differentiation by increasing
      vesicle transport activity in the Golgi apparatus and inhibiting the lipolysis of
      LDs.

PMID- 30291781
TI  - Formylglycine-generating enzymes for site-specific bioconjugation.
AB  - Site-specific bioconjugation strategies offer many possibilities for directed
      protein modifications. Among the various enzyme-based conjugation protocols,
      formylglycine-generating enzymes allow to posttranslationally introduce the amino
      acid Calpha-formylglycine (FGly) into recombinant proteins, starting from
      cysteine or serine residues within distinct consensus motifs. The aldehyde
      bearing FGly-residue displays orthogonal reactivity to all other natural amino
      acids and can, therefore, be used for site-specific labeling reactions on protein
      scaffolds. In this review, the state of research on catalytic mechanisms and
      consensus motifs of different formylglycine-generating enzymes, as well as
      labeling strategies and applications of FGly-based bioconjugations are presented.

PMID- 30291782
TI  - Non-invasive improved technique for lumbar discus hernia classification based on
      fuzzy logic.
AB  - This paper presents the improved technique for classification of the type of
      lumbar discus hernia based on fuzzy logic. The reduced mobility of the foot is
      one of the symptoms of the disease that occurs because of the displaced discs in
      the space of two vertebrae. This fact was used for non-invasive discus hernia
      diagnosis by measuring force values from four sensors placed on both feet (first,
      second and fourth metatarsal head as well as the heel). Hardware and software
      systems were constructed for the doctor to perform the measurements and have a
      graphical representation during the measuring procedure. The procedure included
      measuring force values of 18 subjects during normal standing, standing on
      forefeet and heels. All subjects were diagnosed by a specialist with either L4/L5
      or L5/S1 discus hernia. Filtering and further preprocessing of acquired values
      included separation of forefeet and heel segments that were used as inputs to
      fuzzy system. The results showed that the accuracy of such a fuzzy system was
      around 72%, and the proposed system correctly recognizes healthy individuals.
      Obtained information about forces on characteristic points on the foot represents
      useful data in diagnosis which further can be processed in order to be a
      supportive tool to doctors.

PMID- 30291783
TI  - Cardiac troponin and natriuretic peptide analytical interferences from hemolysis
      and biotin: educational aids from the IFCC Committee on Cardiac Biomarkers (IFCC
      C-CB).
AB  - Two interferences recently brought to the forefront as patient safety issues
      include hemolysis (hemoglobin) and biotin (vitamin B7). The International
      Federation for Clinical Chemistry Committee on Cardiac Biomarkers (IFCC-CB)
      obtained input from a majority of cTn and NP assay manufacturers to collate
      information related to high-sensitivity (hs)-cTnI, hs-cTnT, contemporary, and POC
      cTn assays, and NP assays interferences due to hemolysis and biotin. The
      information contained in these tables was designed as educational tools to aid
      laboratory professionals and clinicians in troubleshooting cardiac biomarker
      analytical results that are discordant with the clinical situation.

PMID- 30291784
TI  - PSA-based, prostate cancer risk on-line calculators: no such thing as a crystal
      ball?

PMID- 30291785
TI  - The associations between mental health, health-related quality of life and
      insulin pump therapy among children and adolescents with type 1 diabetes.
AB  - Background Diabetes has previously been linked to mental health problems in
      children and adolescents, but more recent studies have yielded mixed findings.
      The aim of the current study was to compare symptoms of mental health problems in
      children and adolescents with and without type 1 diabetes (T1DM). Methods Life
      quality, subjective well-being, self-rated health, depression and somatic
      symptoms in children and adolescents with diabetes (n=130) were measured and
      compared to the results of a socio-demographically joined control group (n=177)
      which consists of healthy children and adolescents. Results A significant
      difference could be observed between the groups in well-being and depressive
      symptoms as according to the results, the research sample namely the children
      with T1DM could be described with significantly higher subjective well-being and
      mood, but with less physical symptoms and lower level of depression as those in
      the control group. Conclusions These findings suggest that T1DM is not associated
      with an increased risk of psychosocial problems, and confirm that even a severe
      disease of a child can lead to personal growth.

PMID- 30291786
TI  - Influence of climate and environmental change in Nigeria: a review on
      vulnerability and adaptation to climate change.
AB  - This paper reviews the current issues that involve environmental changes in
      Nigeria and environmental threats within the country. The fundamental aim of
      scientific knowledge in environmental studies is to reconcile climate change and
      environmental sustainability with developmental goals. Therefore, information on
      impact adaptation to climate change and vulnerability research is required to
      develop specific, action-oriented, interdisciplinary, successful, sociopolitical
      and democratic reform for the entire population of a country. This condition
      requires large inclusion of environmental researchers, institutions, re-inventing
      of research structures and ideas to dominate the global environmental change
      research and the critical analysis of present decision making, power, structure
      and related information structures. This review presents the effect of climate
      change in Nigeria and encourages adaptation research with challenging innovation,
      such as the use of energy-efficient renewable energy sources to significantly
      reduce greenhouse gas emissions. This paper also highlighted the need for
      researchers to become detailed, action oriented and multiscalar and to attend
      communications structure problems in enhancing the environmental activity.

PMID- 30291787
TI  - Rats selectively bred for showing divergent behavioral traits in response to
      stress or novelty or spontaneous yawning with a divergent frequency show similar
      changes in sexual behavior: the role of dopamine.
AB  - Sexual behavior plays a fundamental role for reproduction in mammals and other
      animal species. It is characterized by an anticipatory and a consummatory phase,
      and several copulatory parameters have been identified in each phase, mainly in
      rats. Sexual behavior varies significantly across rats even when they are of the
      same strain and reared under identical conditions. This review shows that rats of
      the same strain selectively bred for showing a divergent behavioral trait when
      exposed to stress or novelty (i.e. Roman high and low avoidance rats, bred for
      their different avoidance response to the shuttle box, and high and low novelty
      exploration responders rats, bred for their different exploratory response to a
      novel environment) or a spontaneous behavior with divergent frequency (i.e. low
      and high yawning frequency rats, bred for their divergent yawning frequency) show
      similar differences in sexual behavior, mainly in copulatory pattern, but also in
      sexual motivation. As shown by behavioral pharmacology and intracerebral
      microdialysis experiments carried out mainly in Roman rats, these sexual
      differences may be due to a more robust dopaminergic tone present in the
      mesocorticolimbic dopaminergic system of one of the two sub-lines (e.g. high
      avoidance, high novelty exploration, and low yawning rat sub-lines). Thus,
      differences in genotype and/or in prenatal/postnatal environment lead not only to
      individual differences in temperament and environmental/emotional reactivity but
      also in sexual behavior. Because of the highly conserved mechanisms controlling
      reproduction in mammals, this may occur not only in rats but also in humans.

PMID- 30291788
TI  - Prognostic Value and Clinicopathologic Features of Platelet Distribution Width in
      Cancer: A Meta-Analysis.
AB  - BACKGROUND The association between platelet distribution width (PDW) and cancer
      has been evaluated by a few studies, but the influence of PDW on cancer prognosis
      is unclear. Therefore, we conducted the present meta-analysis. MATERIAL AND
      METHODS We identified relevant research using identical search strategies. The
      influence of PDW level on cancer prognosis, as well as clinical characteristics,
      was analyzed. RESULTS A total of 11 studies comprising 2625 cancer patients were
      included in our meta-analysis. The results suggested that high PDW level was
      obviously related to poor OS (HR=1.54, 95%CI 1.18-2.00), especially for breast
      cancer (HR=1.21, 95%CI 1.07-1.36) and pharyngolaryngeal cancer (HR=3.06, 95%CI
      1.68-5.57). Furthermore, high PDW was obviously related to poor OS both in older
      and younger subgroups, with combined HR estimates of 1.58 (95%CI 1.15-2.16) and
      1.64 (95%CI 1.19-2.26), respectively. High PDW level was notably related to poor
      OS in the cut-off value 316% subgroup (HR=1.84, 95%CI 1.01-3.40). Moreover, high
      PDW level was obviously associated with lymph node metastasis (OR=1.43, 95%CI
      1.04-1.99). CONCLUSIONS The findings of this study suggest that PDW is an
      effective and convenient indicator of cancer prognosis. Furthermore, high PDW
      level is obviously associated with lymph node metastasis.

PMID- 30291789
TI  - Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old
      or older with locally advanced oropharyngeal carcinoma.
AB  - BACKGROUND: The comparative efficacy of cisplatin (CDDP), carboplatin, and
      cetuximab (CTX) delivered concurrently with radiation for locally advanced
      oropharyngeal squamous cell carcinoma continues to be evaluated. METHODS: The
      linked Surveillance, Epidemiology, and End Results-Medicare database was used to
      identify and compare patient and disease profiles, mortality, toxicity, and
      overall cost for patients with oropharynx cancer undergoing definitive concurrent
      chemoradiation with CDDP, carboplatin, or CTX between 2006 and 2011. The human
      papillomavirus status was unknown. The primary outcome was 2-year overall
      survival (OS). RESULTS: Four hundred nine patients receiving concurrent CDDP (n =
      167), carboplatin (n = 69), or CTX (n = 173) were included. Those who were older,
      those who were nonwhite, and those with a Charlson Comorbidity Index >= 2 were
      less likely to receive CDDP. Two-year OS was inferior with CTX (hazard ratio
      [HR], 1.68; 95% confidence interval [CI], 1.08-2.60; P = .020) and no different
      with carboplatin (HR, 1.31; 95% CI, 0.73-2.35; P = .362) in a Cox proportional
      hazards model (reference CDDP). There was no statistically significant difference
      between carboplatin and CTX (HR, 1.28; 95% CI, 0.77-2.14; P = .891). Rates of
      antiemetic use and hospital visits for nausea/emesis/diarrhea or dehydration were
      statistically higher with CDDP. Pneumonia rates were higher with carboplatin. In
      the multivariate model, the corrected mean per-patient spending was significantly
      higher for CTX and carboplatin than CDDP ($61,133 and $65,721 vs $48,709).
      CONCLUSIONS: Patients who received CDDP had improved OS. CDDP was also associated
      with slightly lower overall costs and higher antiemetic usage and hospital visit
      rates, although a strong selection bias was observed because those receiving CTX
      and carboplatin were older and had higher comorbidity scores.

PMID- 30291790
TI  - FNA of epithelioid sarcoma: Curie Institute experience and critical review of the
      literature.
AB  - BACKGROUND: Epithelioid sarcoma (ES) is a rare mesenchymal tumor that is divided
      into 2 types: classic and proximal. To the authors' knowledge, ES has been poorly
      studied in cytology, with fewer than 50 cases reported to date. The objective of
      the current study was to analyze the cytological and immunohistochemical
      information regarding 5 cases of ES. METHODS: Five cases of ES were analyzed: 4
      of proximal type and 1 of classic type. The cases were taken from 4 female
      patients and 1 male patient. The patients ranged in age from 10 to 75 years.
      RESULTS: All smears obtained from the proximal type of ES were found to be
      hypercellular with a necrotic and inflammatory background. Smears from classic
      type ES were hypocellular with a hemorrhagic background. Large, dispersed
      epithelioid cells and loosely cohesive groups of cells were most frequently noted
      in all cases. All cases of proximal-type ES demonstrated rhabdoid cells and
      marked nuclear atypia, but in only one case were rhabdoid cells found to be
      dominant. ES diagnoses were confirmed by immunohistochemistry in histological
      material. In 4 cases, epithelial marker expression was noted, whereas CD34 was
      found to be positive in only the classic type of ES. In 2 cases, total loss of
      SMARCB1/INI1 nuclear expression was observed. In the 2 SMARCB1/INI1-positive
      cases, loss of SMARCA2/BRM expression was observed in one case and partial loss
      was observed in the other case. CONCLUSIONS: The proximal type of ES differs from
      the classic type by the presence of rhabdoid cells and marked nuclear atypia. A
      specific immunohistochemical profile demonstrating loss of SMARCB1/INI1 or other
      proteins from the SWI/SNF complex also may be indicative of this diagnosis.

PMID- 30291791
TI  - Optimal treatment of early stage HER2-positive breast cancer.
AB  - Significant advances have occurred in the treatment of human epidermal growth
      factor receptor 2 (HER2)-positive breast cancer that have changed its natural
      history. The addition of trastuzumab to standard therapy has dramatically
      improved the prognosis for patients with early stage, HER2-positive breast cancer
      to unprecedented survival outcomes. Yet, long-term follow-up data from adjuvant
      pivotal trials indicate that 15-24% of patients still develop recurrent disease.
      Most of the research has focused on the addition of novel anti-HER2 drugs to
      standard therapy, including studies evaluating the monoclonal antibody
      pertuzumab; the antibody-drug conjugate trastuzumab-emtansine (T-DM1); the
      selective, reversible HER2/epidermal growth factor receptor kinase inhibitor
      lapatinib; or the irreversible pan-HER2 inhibitor neratinib. Dual HER2 blockade
      has improved overall survival remarkably in metastatic breast cancer; however, in
      patients with early stage disease, it has led to small benefits in progression
      free survival. Moreover, biologic heterogeneity within HER2-positive disease may
      determine response to treatment and prognosis. Different subgroups of patients
      with HER2-positive breast cancer may benefit from different therapeutic
      approaches. Thus, there is ongoing work to optimize and de-escalate treatment in
      patients who may do just as well with less therapy and can avoid unnecessary
      treatments and their related toxicities. The objective of this review is to
      summarize the background and latest evidence on the current management of early
      stage, HER2-positive breast cancer and to present novel perspectives on its
      management.

PMID- 30291792
TI  - Toward the potential cure of leukemias in the next decade.
AB  - Historically, progress in leukemia research has been slow, but it has accelerated
      recently as a result of understanding the pathophysiology of leukemias and
      implementing more effective and targeted therapies. This review summarizes the
      progress across leukemia subsets and projects the potential cure of most
      leukemias in the next decade.

PMID- 30291794
TI  - A Single Extracellular Vesicle (EV) Flow Cytometry Approach to Reveal EV
      Heterogeneity.
AB  - Extracellular vesicles (EVs) actively participate in intercellular communication
      and pathological processes. Studying the molecular signatures of EVs is key to
      reveal their biological functions and clinical values, which, however, is greatly
      hindered by their sub-100 nm dimensions, the low quantities of biomolecules each
      EV carries, and the large population heterogeneity. Now, single-EV flow cytometry
      analysis is introduced to realize single EV counting and phenotyping in a
      conventional flow cytometer for the first time, enabled by target-initiated
      engineering (TIE) of DNA nanostructures on each EV. By illuminating multiple
      markers on single EVs, statistically significant differences are revealed among
      the molecular signatures of EVs originating from several breast cancer cell
      lines, and the cancer cell-derived EVs among the heterogeneous EV populations are
      successfully recognized. Thus, our approach holds great potential for various
      biological and biomedical applications.

PMID- 30291793
TI  - Klinefelter syndrome in males with germ cell tumors: A report from the Children's
      Oncology Group.
AB  - BACKGROUND: Males with Klinefelter syndrome (KS) (47,XXY) may be more likely to
      develop germ cell tumors (GCTs), particularly mediastinal GCTs. To date, there
      are no reports characterizing the prevalence of KS among male GCT cases. METHODS:
      The authors used array genotyping data from a Children's Oncology Group
      epidemiology study to estimate the prevalence of KS in males with GCTs (433 males
      aged birth-19 years). Using Fisher's exact tests, the authors examined
      differences in age at diagnosis, race/ethnicity, tumor location and histology,
      and several birth characteristics between cases of KS-GCT and GCT cases without
      chromosomal abnormalities. Using publicly available data, the authors estimated
      the 1-year risk, risk ratio, and corresponding 95% confidence interval of GCTs
      among KS cases. RESULTS: Based on analysis of array genotyping data, 3% of male
      GCT cases (13 cases) had KS. The additional X chromosome was of maternal origin
      in 7 of the 13 cases. Of these 13 KS cases, 5 of 9 KS-GCT cases with parental
      questionnaire data (56%) reported a diagnosis of KS. No significant differences
      were observed with regard to patient or birth characteristics between KS-GCT and
      non-KS-GCT cases. KS-GCT cases were significantly more likely to be diagnosed
      with mediastinal tumors than non-KS-GCT cases (P<.01). The authors estimated the
      risk of developing a GCT among males with KS to be 0.00025, or 1 per 4000 males
      (risk ratio, 18.8; 95% confidence interval, 11.7-30.0). CONCLUSIONS: Compared
      with males without chromosomal abnormalities, males with KS are more likely to be
      diagnosed with a mediastinal GCT. The presence of KS should be considered in
      males with a diagnosis of mediastinal GCT. In the current study, the authors
      report that approximately one-third of males with mediastinal germ cell tumors
      have Klinefelter syndrome, and therefore screening of these individuals for the
      syndrome may be warranted. Males with Klinefelter syndrome are 19 times as likely
      as males without Klinefelter syndrome to develop germ cell tumors.

PMID- 30291795
TI  - Intermolecular Dehydrative Coupling and Intramolecular Cyclization of Ruthenium
      Vinylidene Complexes Formed from Aromatic Propynes Containing Carbonyl
      Functionalities.
AB  - A remarkable intermolecular dehydrative coupling reaction with the formation of a
      C-C bond was found for the vinylidene complex 2 a, yielding the dinuclear
      bisvinylidene complex 4 a. Complex 2 a containing 1-hydroxyindan moiety was first
      formed from the reaction of o-propynyl benzaldehyde 1 a with [Ru]-Cl
      ([Ru]=Cp(PPh3 )2 Ru) by a cyclization process. For analogous aldehyde 1 b
      containing an additional 1,3-dioxolane group on the aryl ring, similar
      intermolecular coupling yields the dinuclear bisvinylidene complex 4 b. However,
      the fluoro group on the aryl ring in aldehyde 1 c inhibits the coupling reaction,
      giving only the vinylidene complex 2 c. For the reactions of [Ru]-Cl in MeOH with
      compounds 1 f, 1 g and 1 h, each with a ketone functionality, cyclization gives
      vinylidene complexes 2 f, 2 g and 2 h, respectively. However, no similar
      intermolecular coupling was observed, instead, the intramolecular dehydration
      yields 8 f, 8 g and 8 h, respectively. In CDCl3 , catalytic cyclization is
      observed for the o-propynylphenyl ketone 1 h with [Ru]-Cl at 50  degrees C giving
      the isochromene products 14 h. Furthermore, treatment of the o-propynylaryl
      alpha,beta-unsaturated ketones 1 k-m and 1 n with [Ru]-Cl in MeOH affords the
      corresponding vinylidene complexes 10 k-m and 11 n each with 1-benzosuberone
      moiety in the presence of NH4 PF6 . These intramolecular cyclization products
      were formed by the addition of Cbeta onto the terminal carbon of the alkene
      moiety. All these reaction products were characterized by spectroscopic methods.
      In addition, structures of complexes 4 a, and 10 l were confirmed by single
      crystal X-ray diffraction analysis.

PMID- 30291796
TI  - Phase 1 study of EGFR-antisense DNA, cetuximab, and radiotherapy in head and neck
      cancer with preclinical correlatives.
AB  - BACKGROUND: Cetuximab combined with radiation therapy (RT) is an evidence-based
      treatment for locally advanced head and neck squamous cell carcinoma (HNSCC);
      however, locoregional failure remains the primary cause of cancer-related death
      in this disease. Intratumoral injection of epidermal growth factor receptor
      (EGFR)-antisense plasmid DNA (EGFR-AS) is safe and has been associated with
      promising lesional responses in patients who have recurrent/metastatic HNSCC. For
      the current study, the authors investigated the antitumor effects of cetuximab
      and EGFR-AS in preclinical HNSCC models and reported their phase 1 experience
      adding intratumoral EGFR-AS to cetuximab RT. METHODS: Antitumor mechanisms were
      investigated in cell line and xenograft models. Phase 1 trial eligibility
      required stage IVA through IVC HNSCC and a measurable lesion accessible for
      repeat injections. Patients received standard cetuximab was for 9 weeks. EGFR-AS
      was injected weekly until they achieved a lesional complete response. RT was
      delivered by conventional fractionation for 7 weeks, starting at week 3. Research
      biopsies were obtained at baseline and week 2. RESULTS: When added to cetuximab,
      EGFR-AS decreased cell viability and xenograft growth compared with EGFR-sense
      control, partially mediated by reduced EGFR expression. Six patients were
      enrolled in the phase 1 cohort. No grade 2 or greater EGFR-AS-related adverse
      events occurred. The best lesional response was a complete response (4 patients),
      and 1 patient each had a partial response and disease progression. EGFR
      expression decreased in 4 patients who had available paired specimens.
      CONCLUSIONS: In preclinical models, dual EGFR inhibition with cetuximab and EGFR
      AS enhanced antitumor effects. In a phase 1 cohort, intratumoral EGFR-AS
      injections, cetuximab, and RT were well tolerated. A phase 2 trial is needed to
      conduct an extended evaluation of safety and to establish efficacy.

PMID- 30291797
TI  - Multimedia psychoeducation for patients with cancer who are eligible for clinical
      trials: A randomized clinical trial.
AB  - BACKGROUND: Supporting patients' decision making about clinical trials may
      enhance trial participation. To date, few theory-based interventions have been
      tested to address this issue. The objective of the current study was aimed to
      evaluate the effect of a multimedia psychoeducation (MP) intervention, relative
      to a print education (PE) intervention, on patients' decision support needs and
      attitudes about clinical trials. METHODS: Patients with cancer who were eligible
      for participation in a National Cancer Institute therapeutic cancer clinical
      trial were recruited through the nationwide University of Rochester Cancer Center
      National Cancer Institute Community Oncology Research Program from 2014 to 2016
      and were randomized to the MP or PE intervention. Assessments at baseline (before
      intervention), postintervention, and at a 2-month follow-up visit included
      patients' decision support needs, attitudes regarding clinical trials, and
      clinical trial participation. RESULTS: In total, 418 patients with various types
      of cancer were recruited (ages 26-89 years). Relative to the PE intervention, the
      MP intervention did not significantly affect decision support needs. However,
      patients in the MP arm reported significantly more positive attitudes about
      clinical trials and were more likely to participate in a clinical trial than
      those in the PE arm (69% vs 62%; P = .01). Furthermore, an improvement in
      attitudes about clinical trials significantly mediated the effect of the
      intervention on participation in clinical trials. CONCLUSIONS: The MP
      intervention was able to improve patient attitudes toward clinical trials
      compared with the PE intervention, and this improvement led to increased rates of
      participation in trials. The MP intervention could be disseminated to improve
      attitudes about clinical trials among patients with cancer.

PMID- 30291798
TI  - Individualized survival prediction for patients with oropharyngeal cancer in the
      human papillomavirus era.
AB  - BACKGROUND: Accurate, individualized prognostication in patients with
      oropharyngeal squamous cell carcinoma (OPSCC) is vital for patient counseling and
      treatment decision making. With the emergence of human papillomavirus (HPV) as an
      important biomarker in OPSCC, calculators incorporating this variable have been
      developed. However, it is critical to characterize their accuracy prior to
      implementation. METHODS: Four OPSCC calculators were identified that integrate
      HPV into their estimation of 5-year overall survival. Treatment outcomes for 856
      patients with OPSCC who were evaluated at a single institution from 2003 through
      2016 were analyzed. Predicted survival probabilities were generated for each
      patient using each calculator. Calculator performance was assessed and compared
      using Kaplan-Meier plots, receiver operating characteristic curves, concordance
      statistics, and calibration plots. RESULTS: Correlation between pairs of
      calculators varied, with coefficients ranging from 0.63 to 0.90. Only 3 of 6
      pairs of calculators yielded predictions within 10% of each other for at least
      50% of patients. Kaplan-Meier curves of calculator-defined risk groups
      demonstrated reasonable stratification. Areas under the receiver operating
      characteristic curve ranged from 0.74 to 0.80, and concordance statistics ranged
      from 0.71 to 0.78. Each calculator demonstrated superior discriminatory ability
      compared with clinical staging according to the seventh and eighth editions of
      the American Joint Committee on Cancer staging manual. Among models, the Denmark
      calculator was found to be best calibrated to observed outcomes. CONCLUSIONS:
      Existing calculators exhibited reasonable estimation of survival in patients with
      OPSCC, but there was considerable variability in predictions for individual
      patients, which limits the clinical usefulness of these calculators. Given the
      increasing role of personalized treatment in patients with OPSCC, further work is
      needed to improve accuracy and precision, possibly through the identification and
      incorporation of additional biomarkers.

PMID- 30291799
TI  - OSCP subunit of mitochondrial ATP synthase: role in regulation of enzyme function
      and of its transition to a pore.
AB  - The permeability transition pore (PTP) is a latent, high-conductance channel of
      the inner mitochondrial membrane. When activated, it plays a key role in cell
      death and therefore in several diseases. The investigation of the PTP took an
      unexpected turn after the discovery that cyclophilin D (the target of the PTP
      inhibitory effect of cyclosporin A) binds to FO F1 (F)-ATP synthase, thus
      inhibiting its catalytic activity by about 30%. This observation was followed by
      the demonstration that binding occurs at a particular subunit of the enzyme, the
      oligomycin sensitivity conferral protein (OSCP), and that F-ATP synthase can form
      Ca2+ -activated, high-conductance channels with features matching those of the
      PTP, suggesting that the latter originates from a conformational change in F-ATP
      synthase. This review is specifically focused on the OSCP subunit of F-ATP
      synthase, whose unique features make it a potential pharmacological target both
      for modulation of F-ATP synthase and its transition to a pore.

PMID- 30291800
TI  - Enrollment on clinical trials does not improve survival for children with acute
      myeloid leukemia: A population-based study.
AB  - BACKGROUND: It is questionable whether enrollment on clinical trials offers any
      survival advantage at the population level over standard-of-care treatment. The
      objectives of this study were to describe the impact of trial enrollment on event
      free survival and overall survival in pediatric acute myeloid leukemia (AML)
      using the Cancer in Young People in Canada (CYP-C) database. METHODS: Children
      were included if they had had AML newly diagnosed between ages birth and 14 years
      from 2001 to 2012. CYP-C is a national pediatric cancer population-based database
      that includes all cases of pediatric cancer diagnosed and treated at 1 of the 17
      tertiary pediatric oncology centers in Canada. Univariate and Cox proportional
      hazards models were used to evaluate the impact of initial trial enrollment on
      survival. RESULTS: In total, 397 eligible children with AML were included in the
      analysis, of whom 94 (23.7%) were enrolled on a clinical trial at initial
      diagnosis. The most common reason for non-enrollment was that no trial was
      available. The event-free survival rate at 5 years was 57.8% +/- 5.2% for those
      enrolled versus 54.8% +/- 2.9% for those not enrolled (P = .75). The overall
      survival rate at 5 years was 70.1% +/- 4.9% for those enrolled versus 66.3% +/-
      2.8% for those not enrolled (P = .58). Enrollment on a trial was not associated
      with improved event-free or overall survival in multiple regression analyses.
      CONCLUSIONS: Enrollment on a clinical trial was not associated with improved
      survival for children with AML in a population-based cohort. Rationale for trial
      enrollment should not include the likelihood of benefit compared with non
      enrollment.

PMID- 30291801
TI  - Respiratory emergency department use from diagnosis through survivorship in
      children, adolescents, and young adults with cancer.
AB  - BACKGROUND: Children and adolescents and young adults (AYAs) with cancer often
      experience severe respiratory morbidity and mortality from the therapies used to
      treat their cancers. Few studies have examined respiratory outcomes among this
      population using emergency department (ED) visits as an objective measure of
      respiratory health. METHODS: ED visits for respiratory conditions were identified
      for children and AYAs diagnosed with cancer, 0-25 years of age, from 1997 through
      2012 (2535 cases) and compared with a birthdate-matched and sex-matched cohort
      without cancer drawn from the general population (7605 controls). Negative
      binomial regression with robust standard errors was used to estimate incidence
      rates, rate ratios (RRs), and 95% confidence intervals for primary respiratory ED
      visits, combined and by diagnosis (asthma, respiratory disease, and respiratory
      infection) from 1997 through 2015. Analyses were performed for new cases (0 to <5
      years from diagnosis) and survivors (5-18 years from diagnosis). RESULTS:
      Subjects were followed for an average of 8 years (range, 0-18 years). Relative to
      the comparison cohort, cancer cases had higher incidence rates for all types of
      respiratory ED visits over both follow-up times. New cases had significantly
      higher RRs for any respiratory condition (RR, 4.14), respiratory disease (RR,
      4.62), and respiratory infection (RR, 4.74). Among survivors, the RRs for any
      respiratory condition (RR, 2.00) and respiratory infection (RR, 2.10) were
      significantly elevated, although the magnitude tended to decline in survivorship.
      Demographic and clinical risk factors found to be associated with respiratory ED
      visits included Hispanic/other race/ethnicity, male sex, exposure to
      chemotherapy, diagnosis at a younger age, and a diagnosis of leukemia.
      CONCLUSIONS: The results of the current study demonstrated that children and AYAs
      with cancer face an increased burden of respiratory complications compared with a
      comparison cohort without cancer from diagnosis through survivorship.

PMID- 30291803
TI  - MicroRNA-146a sponge therapy suppresses neointimal formation in rat vein grafts.
AB  - The long-term failure of vein grafts due to neointimal hyperplasia remains a
      difficult problem in cardiovascular surgery. Exploring novel approaches to
      prevent neointimal hyperplasia is important. MicroRNA-146a (miR-146a) plays an
      essential role in promoting vascular smooth muscle cell (VSMC) proliferation.
      Thus, the aim of the present study is to investigate whether adenovirus-mediated
      miR-146a sponge (Ad-miR-146a-SP) gene therapy could attenuate neointimal
      formation in rat vein grafts. (Ad-miR-146a-SP) was constructed to transfect
      cultured VSMCs and grafted veins. To improve the efficiency of transferring the
      miR-146a sponge gene into the grafted veins, 20% poloxamer F-127 gel incorporated
      with 0.25% trypsin was used to increase adenovirus contact time and penetration.
      miR-146a-SP transduction significantly reduced the expression of miR-146a both in
      cultured VSMCs and vein grafts. miR-146a sponge markedly attenuated VSMC
      proliferation and migration. Consistent with this, miR-146a sponge gene therapy
      significantly attenuated neointimal formation and also improved blood flow in the
      vein grafts. Mechanistically, we identified the Kruppel-like factor 4(KLF4) as a
      potential downstream target gene of miR-146a in vein grafts. Our data show that
      miR-146a sponge gene therapy could effectively reduce miR-146a activity and
      attenuate neointimal formation in vein grafts, suggesting its potential
      therapeutic application for prevention of vein graft failure. (c) 2018 IUBMB
      Life, 2018.

PMID- 30291804
TI  - A prospective comparison of cancer clinical trial availability and enrollment
      among adolescents/young adults treated at an adult cancer hospital or affiliated
      children's hospital.
AB  - BACKGROUND: Low cancer clinical trial (CCT) enrollment may contribute to survival
      disparities affecting adolescents and young adults (AYAs) (ages 15-39 years). The
      objective of this study was to evaluate whether differences in CCT availability
      related to treatment site could explain the low CCT enrollment. METHODS: This
      prospective, observational cohort study was conducted at an academic children's
      hospital and its affiliated but geographically separated adult cancer hospital
      within a National Cancer Institute-designated Comprehensive Cancer Center. For
      consecutive, newly diagnosed AYA patients, it was determined whether an
      appropriate CCT existed nationally, was available at the treatment site, and was
      used for enrollment. Proportions of AYAs in these categories were compared
      between sites using the chi-square test. RESULTS: One hundred fifty-two
      consecutive AYA patients were included from the children's hospital (n = 68; ages
      15-20 years) and the adult cancer hospital (n = 84; ages 18-39 years). Although
      there was no difference in CCT existence for individual AYA patients by site
      (children's hospital [36 of 68 patients; 52.9%] vs adult cancer hospital [45 of
      84 patients; 53.6%]; P = .938), CCT availability was significantly lower at the
      adult cancer hospital (14 of 84 patients [16.7%] vs 30 of 68 [44.1%] at the
      children's hospital; P < .001). The proportion of AYAs enrolled was low at both
      sites (8 of 68 patients [11.8%] vs 6 of 84 patients [7.1%], respectively; P =
      .327). Fewer existing CCTs were available at the adult cancer hospital (4 of 27
      patients [14.8%] vs 8 of 14 patients [57.1%], respectively), and those were
      directed toward solid tumors and new agents. CONCLUSIONS: Efforts to improve low
      CCT enrollment among AYAs should be differentiated by treatment site. In the
      adult setting, these efforts should be aimed at improving CCT availability by
      overcoming site-level barriers to opening existing CCTs.

PMID- 30291805
TI  - Perioperative biobehavioral interventions to prevent cancer recurrence through
      combined inhibition of beta-adrenergic and cyclooxygenase 2 signaling.
AB  - Evidence suggests that excess perioperative activation of the sympathetic nervous
      system and the consequent release of catecholamines (ie, epinephrine and
      norepinephrine) in the context of cancer surgery and inflammation may
      significantly facilitate prometastatic processes. This review first presents
      biomedical processes that make the perioperative timeframe pivotal in determining
      long-term cancer outcomes nonproportionally to its short duration (days to
      weeks). Then, it analyzes the various mechanisms via which the excess release of
      catecholamines can facilitate the progression of cancer metastases in this
      context by directly affecting the malignant tissues and by regulating, via
      indirect pathways, immunological and other mechanisms that affect metastatic
      progression in the tumor microenvironment and systemically. In addition, this
      review addresses the need to supplement beta-adrenoreceptor blockade with
      cyclooxygenase 2 inhibition, especially during surgery and shortly thereafter,
      because similar mechanisms are simultaneously activated by surgery-induced
      inflammatory responses. Importantly, this review presents translational and
      clinical evidence showing that perioperative beta-adrenoreceptor blockade and
      cyclooxygenase 2 inhibition can reduce the prometastatic process and cancer
      recurrence, and the clinical feasibility and safety of this approach are
      demonstrated as well. Lastly, alternative psychophysiological approaches to the
      use of beta-adrenergic blockers are presented because a substantial portion of
      patients have medical contraindications to this pharmacological treatment. The
      adaptation of existing psychophysiological interventions to the perioperative
      period and principles for constructing new approaches are discussed and
      exemplified. Overall, pharmacobehavioral interventions, separately or in
      combination, could transform the perioperative timeframe from being a prominent
      facilitator of metastatic progression to an opportunity for arresting or
      eliminating residual disease, potentially improving long-term survival rates in
      cancer patients.

PMID- 30291806
TI  - Investigation of the Reaction Pathways of Biomass-Derived Oxygenate Conversion
      into Monoalcohols in Supercritical Methanol with CuMgAl-Mixed-Metal Oxide.
AB  - Reaction pathways for the conversion of cellulose into C2 -C6 monoalcohols by
      supercritical methanol depolymerization and hydrodeoxygenation (SCM-DHDO) over a
      CuMgAl oxide catalyst have been elucidated using a range of model compounds. SCM
      DHDO of intermediate oxygenates including glycerol, methyl lactate, and 1,2
      ethanediol produces similar products as those produced from the SCM-DHDO of
      cellulose. The pathway to C2 -C6 monoalcohols occurs through rapid C-C coupling
      reactions between methanol and diols followed by C-C scission between vicinal
      alcohol groups to produce two monoalcohols. Methyl-branched monoalcohols are
      produced through a methyl shift in a secondary diol followed by dehydration.
      Esters are produced by dehydrogenative coupling between an adsorbed methoxy and a
      primary alcohol. Both dehydrogenation to a ketone and esterification to a methyl
      ester are in equilibrium with the corresponding alcohol and were reversible.
      Dehydration of diols is the slowest observed reaction and not a main pathway to
      monoalcohols. SCM-DHDO of glucose, dihydroxyacetone, and cellulose all produced
      similar high molecular weight species indicating that condensation of
      intermediates can produce undesired side products.

PMID- 30291807
TI  - Will my child do better if she enrolls in a clinical trial?
AB  - The question of whether children with cancer who enroll in clinical trials have
      superior outcomes compared with those who do not participate has been pursued for
      more than 4 decades, and recent studies have provided conflicting answers.
      Whether clinical trial participation influences outcome has important
      implications for how clinicians should present trial participation to patients
      and families. Methodological challenges limit generalizations about the impact of
      clinical trial participation on outcome compared with nonparticipation.
      Oncologists should inform patients and families that clinical trials are the
      engine for future progress because they identify more effective therapies and
      that clinical trial participation is a reasonable option to consider for children
      with cancer. However, as noted in by Truong and colleagues in this issue, the
      rationale for trial enrollment should not include an expectation of better
      outcomes compared with nonenrollment.

PMID- 30291808
TI  - Phytochemicals as mediators for host range expansion of a native invasive forest
      insect herbivore.
AB  - Mountain pine beetle (MPB) has recently invaded jack pine forests in western
      Canada. This invasion signifies a climate change-induced range expansion by a
      native insect. The mechanism underlying this invasion is unknown, but likely
      involves phytochemicals that play critical roles in MPB biology. Thus far,
      studies have investigated the compatibility of jack pine chemistry with beetles
      and their microbial symbionts. I have identified three phytochemical mechanisms
      that have likely facilitated the host range expansion of MPB. First, jack pine
      chemistry is overall similar to that of the historical hosts of MPB. In
      particular, jack pine chemistry is compatible with beetle pheromone production,
      aggregation on host trees and larval development. Furthermore, the compatibility
      of jack pine chemistry maintains beneficial interactions between MPB and its
      microbial symbionts. Second, compared with historical hosts, the novel host not
      only has lower concentrations of toxic and repellent defense chemicals, but also
      contains large concentrations of chemicals promoting host colonization by MPB.
      These patterns are especially pronounced when comparing novel hosts with well
      defended historical hosts. Finally, before MPBs arrived in jack pine forests,
      they invaded a zone of hybrids of novel and historical hosts that likely improved
      beetle success on jack pine, as hybrids show chemical characteristics of both
      hosts. In conclusion, the phytochemistry of jack pine has likely facilitated the
      biological invasion of this novel host by MPB.

PMID- 30291809
TI  - Role of clathrin-mediated endocytosis in the use of heme and hemoglobin by the
      fungal pathogen Cryptococcus neoformans.
AB  - Heme is a major source of iron for pathogens of humans, and its use is critical
      in determining the outcome of infection and disease. Cryptococcus neoformans is
      an encapsulated fungal pathogen that causes life-threatening infections in
      immunocompromised individuals. C. neoformans effectively uses heme as an iron
      source, but the underlying mechanisms are poorly defined. Non-iron
      metalloporphyrins (MPPs) are toxic analogues of heme and are thought to enter
      microbial cells via endogenous heme acquisition systems. We therefore carried out
      a mutant screen for susceptibility against manganese MPP (MnMPP) to identify new
      components for heme uptake in C. neoformans. We identified several genes involved
      in signalling, DNA repair, sugar metabolism, and trafficking that play important
      roles in susceptibility to MnMPP and in the use of heme as an iron source. We
      focused on investigating the role of clathrin-mediated endocytosis (CME) and
      found that several components of CME including Chc1, Las17, Rvs161, and Rvs167
      are required for growth on heme and hemoglobin and for endocytosis and
      intracellular trafficking of these molecules. We show that the hemoglobin uptake
      process in C. neoformans involves clathrin heavy chain, Chc1, which appears to
      colocalise with hemoglobin-containing vesicles and to potentially assist in
      proper delivery of hemoglobin to the vacuole. Additionally, C. neoformans strains
      lacking Chc1, Las17, Rvs161, or Rvs167 were defective in the elaboration of
      several key virulence factors, and a las17 mutant was avirulent in a mouse model
      of cryptococcosis. Overall, this study unveils crucial functions of CME in the
      use of heme iron by C. neoformans and reveals a role for CME in fungal
      pathogenesis.

PMID- 30291810
TI  - Synchrotron radiation microtomography of brain hemisphere and spinal cord of a
      mouse model of multiple sclerosis revealed a correlation between capillary
      dilation and clinical score.
AB  - Multiple sclerosis is a neurological disorder in which the myelin sheaths of
      axons are damaged by the immune response. We report here a three-dimensional
      structural analysis of brain and spinal cord tissues of a mouse model of multiple
      sclerosis, known as experimental autoimmune encephalomyelitis (EAE). EAE-induced
      mice were raised with or without administration of fingolimod, which is used in
      the treatment of multiple sclerosis. Brains and spinal cords dissected from the
      EAE mice were lyophilized so as to reconstitute the intrinsic contrast of tissue
      elements, such as axons, in X-ray images. Three-dimensional structures of the
      brain hemispheres and spinal cords of the EAE mice were visualized with
      synchrotron radiation microtomography. Microtomographic cross sections
      reconstructed from the X-ray images revealed dilation of capillary vessels and
      vacuolation in the spinal cord of the EAE mice. Vacuolation was also observed in
      the cerebellum, suggesting that the neuroinflammatory response progressed in the
      brain. The vessel networks and vacuolation lesions in the spinal cords were
      modelled by automatically tracing the three-dimensional image in order to analyze
      the tissue structures quantitatively. The results of the analysis indicated that
      the distribution of vacuolations was not uniform but three-dimensionally
      localized. The mean vessel diameter showed a linear correlation with the clinical
      score, indicating that vasodilation is relevant to paralysis severity in the
      disease model. We suggest that vasodilation and vacuolation are related with
      neurological symptoms of multiple sclerosis.

PMID- 30291812
TI  - Changes in cardiovascular disease risk and risk factors among women with and
      without breast cancer.
AB  - BACKGROUND: Cardiovascular disease (CVD) risk is an important health concern
      among survivors of breast cancer. However, few studies to date have examined
      whether trajectories of CVD risk and major risk factors are worse among women
      with a breast cancer diagnosis compared with those without. METHODS: Changes in
      weight, body mass index, waist circumference, systolic blood pressure, and 10
      year CVD risk were compared between women with (813 women) and without (1049
      women) an incident breast cancer diagnosis while they were enrolled in the
      National Institute of Environmental Health Sciences Sister Study cohort. Blood
      pressure and adiposity measures were collected by trained examiners at an
      enrollment visit (>=1 year before breast cancer diagnosis) and a second home
      visit 4 to 11 years later (>=1 year after breast cancer diagnosis). The non
      laboratory-based Framingham risk score, a measure of 10-year general CVD risk,
      was calculated at both the enrollment and second visits. All analyses were
      stratified by menopausal status at the time of enrollment. RESULTS: Women who
      were premenopausal at the time of enrollment experienced moderate increases in
      weight, waist circumference, systolic blood pressure, and CVD risk over the study
      period. Those who were postmenopausal at the time of enrollment demonstrated
      little change in weight, but were found to have increases in waist circumference,
      systolic blood pressure, and CVD risk. In both groups, changes over time did not
      differ significantly according to breast cancer status. Neither chemotherapy nor
      endocrine therapy were found to be associated with greater increases in CVD risk
      or risk factors. CONCLUSIONS: In the current study cohort, changes over time in
      CVD risk, adiposity measures, and blood pressure were similar between women who
      developed an incident breast cancer and those who did not.

PMID- 30291811
TI  - Self-reported fatigue in children with advanced cancer: Results of the PediQUEST
      study.
AB  - BACKGROUND: Pediatric cancer-related fatigue is prevalent and significantly
      impairs health-related quality of life, yet its patterns and correlates are
      poorly understood. The objectives of this study were to describe fatigue as
      prospectively reported by children with advanced cancer and to identify the
      factors associated with fatigue and associated distress. METHODS: Children (age
      >=2 years) with advanced cancer (N = 104) or their parents at 3 academic
      hospitals reported symptoms at most weekly over 9 months using the computer-based
      Pediatric Quality of Life Evaluation of Symptoms Technology (PediQUEST) system.
      PediQUEST administered a modified version of the Memorial Symptom Assessment
      Scale (PQ-MSAS) as part of a randomized controlled trial. Clinical information
      was abstracted from medical records. Primary outcomes were: 1) fatigue prevalence
      (yes/no response to PQ-MSAS fatigue item) and 2) fatigue distress (composite
      score of severity, frequency, and bother). Multivariable models were constructed
      to identify factors independently associated with fatigue prevalence and scores
      reflecting fatigue distress (ie, burden). RESULTS: Of 920 reports, 46% (n = 425)
      noted fatigue. When reported, fatigue was of high frequency in 41% of respondents
      (n = 174), severity in 25%of respondents (n = 107), and bother in 34%of
      respondents (n = 143). Most reports (84%; n = 358) were associated with scores
      indicating fatigue distress. In multivariable analyses, fatigue was associated
      with older age, lower hemoglobin, and distress from particular symptoms
      (anorexia, nausea, sleep disturbance, sadness, and irritability). In contrast,
      fatigue distress was associated with distress from nausea, cough, and pain.
      CONCLUSIONS: Fatigue is common among children with advanced cancer and is often
      highly distressing. Interventions focused on uncontrolled symptoms may ease
      fatigue distress in children with advanced cancer.

PMID- 30291813
TI  - Validating the predictors of outcomes after radical cystectomy for bladder
      cancer.
AB  - BACKGROUND: An assessment of surgical risk is essential for patient counseling
      and decision making, and it can provide rationale adjustment for patient
      populations as health care moves from a fee-for-service to a value-based
      reimbursement model. The modified Frailty Index (mFI) has been proposed as a risk
      stratification tool for radical cystectomy (RC), and the objective of the current
      study was to validate this potential use of the mFI using an institutional
      cohort. METHODS: A retrospective review of all patients who underwent RC for
      bladder cancer was conducted at the authors' institution from 2012 to 2016. In
      addition to detailed clinicopathologic and treatment parameters, patients were
      categorized according to the mFI, the Charlson Comorbidity Index (CCI), and the
      American Society of Anesthesiologists (ASA) classification. Covariates were
      analyzed to determine associations with 1-month complication rates (according to
      the Clavien-Dindo system), 3-month readmission rates, hospitalization length, and
      hospitalization costs. RESULTS: In total, 346 patients were included in the
      analysis. The overall complication rate was 56.6%, the major (Clavien grade >=3)
      complication rate was 19.4%, and the readmission rate was 27.9%. Receiver
      operating curve analysis demonstrated a weak association of all indices with
      major complications after RC: the area under the curve was 0.535 (95% confidence
      interval [CI], 0.460-0.611) for the ASA classification; 0.565 (95% CI, 0.485
      0.645) for the CCI score; and 0.551 (95% CI, 0.471-0.631) for the mFI. There were
      no significant differences in the rate of major complications when stratifying
      the results according to the mFI, CCI, or ASA class. Length of hospitalization
      and associated costs were correlated with mFI. CONCLUSIONS: Frailty was not
      associated with postoperative complications and provided little additional
      predictive ability over the ASA classification and the CCI score. Further
      research is required to identify patients who are likely to suffer significant
      complications after RC.

PMID- 30291814
TI  - Massive mitochondrial DNA content in diplonemid and kinetoplastid protists.
AB  - The mitochondrial DNA of diplonemid and kinetoplastid protists is known for its
      suite of bizarre features, including the presence of concatenated circular
      molecules, extensive trans-splicing and various forms of RNA editing. Here we
      report on the existence of another remarkable characteristic: hyper-inflated DNA
      content. We estimated the total amount of mitochondrial DNA in four kinetoplastid
      species (Trypanosoma brucei, Trypanoplasma borreli, Cryptobia helicis, and
      Perkinsela sp.) and the diplonemid Diplonema papillatum. Staining with 4',6
      diamidino-2-phenylindole and RedDot1 followed by color deconvolution and
      quantification revealed massive inflation in the total amount of DNA in their
      organelles. This was further confirmed by electron microscopy. The most extreme
      case is the ~260 Mbp of DNA in the mitochondrion of Diplonema, which greatly
      exceeds that in its nucleus; this is, to our knowledge, the largest amount of DNA
      described in any organelle. Perkinsela sp. has a total mitochondrial DNA content
      ~6.6* greater than its nuclear genome. This mass of DNA occupies most of the
      volume of the Perkinsela cell, despite the fact that it contains only six protein
      coding genes. Why so much DNA? We propose that these bloated mitochondrial DNAs
      accumulated by a ratchet-like process. Despite their excessive nature, the
      synthesis and maintenance of these mtDNAs must incur a relatively low cost,
      considering that diplonemids are one of the most ubiquitous and speciose protist
      groups in the ocean. (c) 2018 IUBMB Life, 70(12):1267-1274, 2018.

PMID- 30291815
TI  - The cytopathologist's expanding role in the 2018 updated molecular testing
      guidelines for lung cancer.

PMID- 30291817
TI  - Perspectives and perceptions of urgent and alert values in surgical pathology and
      cytopathology: A survey of clinical practitioners and pathologists.
AB  - In previous editorials, Chapman and Otis in 2011 and Layfield in 2014 have
      summarized much of the work responsible for establishing the concept of critical
      diagnoses in surgical pathology and cytopathology. Both editorials end with a
      list of 8 key policy points needed for an effective strategy of handling and
      communicating critical diagnoses. We have developed and distributed a Web-based
      survey to elicit clinicians' attitudes regarding many of those key policy points,
      such as how, when, and to whom critical diagnoses should be reported; we have
      allowed some level of collaboration with the clinical staff when developing our
      communication policies as the Association of Directors of Anatomic and Surgical
      Pathology (ADASP) consensus statement recommends. We have identified important
      areas of disagreement between pathologists and clinicians regarding what entities
      should be considered critical and who should be responsible for correlating
      histologic findings with the larger clinical context. Identifying these
      discordant points of view and fostering interdepartmental agreement on the best
      practices in the communication of critical diagnoses is an important patient care
      and safety issue. Chapman and Otis have also suggested the importance of
      increased access to accurate patient information and the clinical history,
      including the level of clinical suspicion of malignancy, and of forming a
      periodic review and quality assurance process. Here we explore methods of
      increasing the ability of pathologists and cytopathologists to identify
      unexpected diagnoses, including optimization of their workstations for better
      access to the electronic medical record, and we examine the progress of quality
      assurance methods in surgical pathology and cytopathology since the ADASP
      consensus statement in 2012.

PMID- 30291816
TI  - Molecular analysis of peripheral lung adenocarcinoma in brush cytology obtained
      by EBUS plus fluoroscopy-guided bronchoscopy.
AB  - BACKGROUND: More than 60% of patients with lung cancer are diagnosed at advanced
      stages. The introduction of targeted therapies requires molecular diagnosis to
      guide treatment. The aim of this study was to evaluate the feasibility of
      performing mutational analysis with brushing specimens obtained by radial
      miniprobe endobronchial ultrasound (R-EBUS) plus fluoroscopy-guided bronchoscopy
      in patients with peripheral pulmonary adenocarcinoma. METHODS: Brushing specimens
      were deposited on cytological slides and were conserved in Roswell Park Memorial
      Institute (RPMI) culture medium. DNA was isolated to perform a mutational
      analysis with real-time quantitative polymerase chain reaction and Sanger
      sequencing for epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma
      viral oncogene homolog (KRAS). RESULTS: Thirty patients with adenocarcinoma were
      prospectively included. In 100% of the patients, the molecular study was viable
      with brushing specimens. In 16 (53.3%), KRAS or EGFR mutations were detected: 10
      KRAS mutations (33.3%) and 6 EGFR mutations (20%). In a comparison with
      histological samples, a correlation of 86.6% was detected, and only 2 patients
      with wild-type results from brushing specimens presented with an EGFR mutation in
      histological samples. CONCLUSIONS: Brushing specimens conserved in RPMI medium
      and obtained by R-EBUS plus fluoroscopy-guided bronchoscopy are valid for
      molecular studies. They allow the detection of EGFR/KRAS mutations in patients
      with peripheral adenocarcinoma. In addition, invasive techniques are avoided, the
      risk of complications is reduced, and the obtained samples are optimized.

PMID- 30291818
TI  - [Study on the Relationship between Soil Emissivity Spectra and Content of Soil
      Elements].
AB  - In this paper, based on the measurements of soil elements content and infrared
      spectra of 26 soil samples collected in more than 10 places, the relationship
      between soil emissivity in mid-infrared bands and the content of 11 soil elements
      including organic matters such as NO(3)-N, P, K, Ca, Mg, Cu, Fe, Mn, Zn and pH
      are analyzed. The bands where the soil elements content are significantly
      correlated with emissivity are given. And soil elements content estimation method
      is established based on the soil emissivity spectra with the partial least
      squares regression model and multiple stepwise regression model. The results show
      that: (1) In 8~10 MUm, the correlation coefficient (R(2)) between Ca and soil
      emissivity is the highest, followed by Mg, Mn and Fe, with the highest
      correlation coefficient of 0.85 and the lowest, 0.52. In the range of 6~8 MUm,
      the correlations between the contents of K, Fe, NO(3)-N, Zn and emissivity
      decrease gradually, with the highest correlation coefficient of 0.75 and the
      lowest 0.48. In 10~14 MUm, the correlation between soil elements contents and
      emissivity is the highest for Mn, followed successively by P and K. (2) The
      scatter plot of soil emissivity and pH value has a parabola relation basically.
      The emissivity is the highest when pH value is 7, while the emissivity decreases
      gradually with the gradual decrease of pH value. (3) The accuracy of the
      estimated soil elements content from the partial least squares regression method
      is higher than that from the multiple stepwise regression method. It is noted
      that R(2) between the measurements and the estimates for the elements of Cu, Fe
      and Ca from the partial least squares regression method are very high (larger
      than 0.9). Additionally, using the simulated emissivity spectrum in the ASTER
      thermal infrared bands, modeling R(2) and validation R(2) between the
      measurements and the estimates for the elements of Ca from the multiple stepwise
      regression method are high (0.774 and 0.892, respectively). Using the simulated
      emissivity spectrum in the MODIS infrared bands, modeling R(2) and validation
      R(2) for Ca and Fe are higher than 0.85, and modeling R(2) and validation R(2)
      for Mg, K are higher than 0.5. As a whole, the emissivity spectrum in ASTER band
      10 and band 11 and MODIS bands 28, 29, 30 are more sensitive to soil elements
      content, and thus they are more suitable for the estimation of soil elements
      content.

PMID- 30291819
TI  - [A Study on Predicting Model of Organic Matter Contend Incorporating Soil
      Moisture Variation].
AB  - Soil organic matter (SOM) is one of the most important measuring indexes of soil
      fertility. How to predict SOM spatial distribution precisely has great
      significance to soil carbon storage estimation and precision agriculture
      development. Traditional measurement of SOM, although with higher accuracy,
      consumes a lot of labor resources and costs long-term monitoring period,
      therefore, it is hard to achieve dynamic monitor of SOM. Spectroscopy technique
      has been used in SOM and other soil physicochemical parameters quick measurement.
      However spatial inversion model accuracy of SOM based on remote sensing images is
      relatively lower than laboratory model accuracy due to the influence of soil
      moisture, roughness and so on. In recent years, most studies have not eliminated
      the effect of moisture. Since moisture has great influence on SOM spectra
      reflectance, this study introduced the temporal information combined with the
      spectral information in order to solve this problem. Soil moisture has
      differences in multi period remote sensing images, and the spectra reflectance is
      also different. Based on the combination of reflectance from of two periods
      remote sensing images, the spectral index was constructed to predict SOM in this
      study. MODIS images of study area acquired in this study area (Blacksoil zone)
      because of the advantage of high temporal resolution. Spectra reflectance of
      MODIS images were used to analyze the effect of moisture on soil spectral
      reflectance, and then the spectral prediction models of SOM were built based on
      the comprehensive impacts of SOM and soil moisture. The results shows that: (1)
      the accuracy of SOM prediction model based on single image was lower without
      consideration of moisture effect, The Root mean square error (RMSE) of SOM
      prediction model were 0.591, 0.522, 0.545, 0.553, and the determination
      coefficient (R(2)) were 0.505, 0.614, 0.562, 0.568, 0.645 respectively based on
      the day of year (DOY) 117, 119, 130, 140, 143 single image. (2) Model with multi
      temporal images (DOY119 and 143) which considered the effect of moisture and SOM
      showed better predictive ability. RMSE was 0.442 while R2 was 0.723. Therefore
      the accuracy and stability of the model were significantly improved, and it can
      be used to predict the spatial distribution of SOM in regional scale. This study
      provides important information for regional soil fertility evaluation, soil
      carbon storage estimation, and precision agriculture development.

PMID- 30291820
TI  - [A Quantitative Analysis of the Reflectance of the Saline Soil under Different
      Disturbance Extent].
AB  - The reflectance of saline soil in the downstream of No.500 reservoir in Fukang,
      Xinjiang province was investigated. Through filed sampling and spectral test,
      using the method of spectral transform, correlation analysis and a quantitative
      analysis were conducted on the salt and water content of the soil under different
      disturbance degree. A multiple linear regression model was established between
      the soil reflectance and soil salinity content. The results show that: first, the
      human disturbance has a significantly positive correlation with the soil content
      while it has an extremely negative correlation with the water content. The
      correlation coefficients are 0.961 and -0.929 respectively. Secondly, it shows
      that those most heavily disturbed soil reflectance is about 10%higher than the
      slightly disturbed, while the slightly disturbed soil reflectance is about 17%
      higher than the undisturbed soil. The reason is that the soil surface of barren
      land with a small amount of vegetation, the biological creature and soil surface
      crust have been destroyed. The more the disturbance is, the greater chance the
      surface layer would be destroyed. Meanwhile, the surface layer of soil will be
      lack of the crust protective; the soil salinity of the bottom rises to the
      surface associated with the soil moisture will quickly evaporate. The salt is
      concentrated to the surface layer due to both little precipitation and a lack of
      protection of soil crust. Thirdly, the peak wavelength location of the spectrum
      is increased (999, 876~979, 1 182~1 370, 1 900 nm) while the soil is taken from
      undisturbed to heavily disturbed conditions, which means that with the increase
      of disturbance, the soil becomes more sensitive in the near infrared region.
      What's more, the three different prediction models are established though the
      reflectance R, the reflectivity of the first derivative R', the reflectance
      R+water. According to the R(2) and the RMSE to comprehensive judge the accuracy
      of the model. It is found that among those established prediction models of the
      same soil salinity in the different levels of disturbance, the smaller the degree
      of human disturbance is, the higher the accuracy of model is. It is found that
      among all of those established prediction models, the one based on the derivative
      of R works the best, of which R(2) is larger than 0.983, model accuracy is
      improved by 5%~10% ,which means that through a derivative transformation, the
      linear noises in the original spectrum can be removed.

PMID- 30291821
TI  - [Characterizing Dissolved Organic Matter (DOM) in Wastewater from Scale Pig Farms
      Using Three-Dimensional Excitation-Emission Matrices (3DEEM].
AB  - The properties of material composition in swine wastewater are closely related to
      its potential environmental effects, and it could provide theoretical bases for
      formulating scientific resource management measures to study the composition of
      organic matter in wastewater. In the present study, swine wastewater was directly
      collected from waste-retention basins in various scale pig farms with a different
      farming scale (based on the annual pig slaughter), namely Cheng Lin (CL, 5 000),
      Wu Yang-gao (WYG, 2 000), Wan Gu (WG, 20 000), and Zhang Bang (ZB, 24 000),
      located in Yujiang County of Jiangxi Province. The main purpose of this study was
      to characterize dissolved organic matter (DOM) in swine wastewater using three
      dimensional excitation-emission matrices (3DEEM) and parallel factor analysis
      (PARAFAC). Results of all samples examined showed, with respect to CL and WYG
      farm, chemical oxygen demand (COD), total nitrogen (TN), ammonium nitrogen
      (NH+4), and dissolved organic carbon (DOC) concentration in swine wastewater was
      significantly higher than WG and ZB farm. Three DOM components, including two
      protein-like components (C1, C2) and one humic-like component (C3), were
      identified in wastewater using 3DEEM and PARAFAC. Results of linear regression
      showed, the fluorescence intensity of C1 linked significantly with C2 (p<0.001)
      and C3 (p<0.001), respectively, suggesting a same source or similar variation
      trend existed possibly between different DOM components. Furthermore, consistent
      with the variation trend of nutrient concentration in wastewater, fluorescence
      intensity of each DOM component in CL and WYG farm was significantly higher than
      WG and ZB farm. The total contribution of C1 and C2 to DOM in swine wastewater
      was CL (89.7%), WG (77.5%), WYG (87.9%), and ZB (72.9%), respectively, and the
      percentage of C3 was CL (10.3%), WG (22.5%), WYG (12.1%), and ZB (27.1%),
      respectively. Thus, the percentage of two protein-like components was
      significantly higher than humic-like in swine wastewater. Meanwhile, the
      fluorescence indices FI370 and humification index (HIX) of WG and ZB farm were
      higher than CL and WYG. In addition, Pearson correlation analysis showed that the
      effects of environmental parameters on fluorescence indices were different, and
      COD and DOC concentrations were significantly correlated with the fluorescence
      intensities of DOM components in swine wastewater. In summary, to a certain
      degree, the nutrient levels affected formation of fluorescence characteristics
      and DOM compositions in swine wastewater between different scale pig farms.

PMID- 30291822
TI  - [Measurement of Soil Organic Matter with Near Infrared Spectroscopy Combined with
      Genetic Algorithm and Successive Projection Algorithm].
AB  - Visible near infrared spectroscopy combined with genetic algorithm and successive
      projection algorithm was investigated to detect soil organic matter (OM). A total
      of 394 soil samples were collected from Wencheng, Zhejiang province. In order to
      simplify calibration model, a total of 18 characteristic wavelengths were
      selected with using genetic algorithm and successive projections algorithm. These
      characteristic wavelengths were subjected to partial least squares regression
      (PLSR) with leave-one-out cross validation to establish calibration model of soil
      organic matter (OM) with coefficient of determination (R2) of 0.81, 0.83, RMSEP
      of 0.22, 0.20 and residual prediction deviation (RPD) of 2.31, 2.45 for the
      calibration set and prediction set respectively. The results showed that using
      genetic algorithm and successive projections algorithm can simplify the model
      greatly while the assessing indexes of model such as R2, RMSEP and RPD were not
      reduced greatly compared with indexes of model using full spectra data to develop
      calibration model. Therefore, genetic algorithm combined with successive
      projections algorithm can be used to simply the model to predict soil organic
      matter.

PMID- 30291823
TI  - [Comparative Study on Laser Induced Breakdown Spectroscopy Based on Single Pulse
      and Re-Heating Orthogonal Dual Pulse].
AB  - In order to improve the detection sensitivity and spectral characteristic of
      laser-induced breakdown spectroscopy (LIBS), re-heating orthogonal dual-pulse
      configuration is adopted to analyze Fe, Pb, Ca and Mg contained in the sample and
      soil sample contained different concentrations of heavy mental Cr. Variation
      relationship between spectral intensity, signal-to-background(SBR) of four
      characteristic spectral lines FeI:404.581 nm,PbI:405.78 nm,CaI:422.67 nm and
      MgI:518.361 nm and time interval of two laser pulses is discussed, the best time
      interval of two laser pulses is obtained 1.0 MUs. In the condition of single
      pulse and dual-pulse, the enhancement factor of spectral intensity of four
      characteristic spectral lines FeI:404.581 nm,PbI:405.78 nm,CaI:422.67 nm and
      MgI:518.361 nm is respectively 2.23,2.31,2.42 and 2.10; The time evolution
      characteristic of spectral intensity of characteristic spectral lines FeI:404.581
      nm and CaI:422.67 nm is considered, and also the variation relationship between
      spectral acquisition delay time and SBR of four characteristic spectral lines,
      dual-pulse can prolong decay time of spectral intensity and improve the SBR of
      characteristic spectral lines; time evolution characteristic of plasma
      temperature and electron density is compared in the condition of single pulse and
      dual-pulse, maximum elevation of plasma temperature is found to be 730 K, and the
      maximum increase of electron density is 1.8*1016 cm-3. The limits of detection of
      heavy mental Cr are obtained 38 and 20 MUg.g-1 respectively in condition of
      single and double pulse, limit of detection of Cr is reduced approximately 2
      times by the condition of re-heating orthogonal dual pulse. Results above
      indicate that re-heating orthogonal dual-pulse can improve detection sensibility
      and spectral characteristic of LIBS technique, which provides an effective method
      for decreasing the limit of detection of elements.

PMID- 30291824
TI  - [Elemental Analysis of Rock with Remote Laser Induced Breakdown Spectroscopy].
AB  - As a kind of spectroscopic technique, the remote laser-induced breakdown
      spectroscopy (Remote LIBS) can qualitatively or quantitatively measure the
      elemental compositions of remote targets with high-power laser and focusing
      optical path. In this work, a Remote LIBS system was designed and established to
      probe the target from 2 to 10 meters. It is characterized with Cassegrain
      telescope structure and automatic focusing technique. Based on this system, a
      method to remotely retrieve the major elemental abundance of rocks is presented.
      With comparative experiment, the influences on spectral signal by pulse laser
      energy, acquisition delay time, integration time, accumulative pulse number are
      analyzed to find out the optimum parameters: the wavelength of laser is 1 064 nm,
      pulse energy is 120 mJ, delay time is 1.5 MUs, integration time is 1 ms, and each
      spectrum data acquired with averaging 30 times detection. 48 pieces of rock
      specimens and 6 kinds of standard rock samples (shale, granite, andesite, basalt,
      gneiss and pegmatite) are selected for the experiment. As to the atomic spectra
      database, 8 characteristic spectral lines of the major elements (SiI390.55
      nm,AlI394.40 nm,AlI396.15 nm,CaII396.85 nm,FeI404.6
      nm,SiI500.60nm,MgI518.36nm,NaI589.59 nm) were extracted for analyses. Then a PLS
      model is constructed to quantitatively analyze the rock elements. 48 rock
      specimens were selected as the training sets to serve the model. The 6 standard
      samples were used to test the solved model. The testing results shows that the
      elemental abundance of Si and Al can be predicted accurately with average
      relative error of only 9.4% and 9.6% respectively.

PMID- 30291825
TI  - Early posttraumatic changes in coagulation and fibrinolysis systems in isolated
      severe traumatic brain injury patients and its influence on immediate outcome.
AB  - OBJECTIVE/BACKGROUND: Early coagulopathy in isolated severe traumatic brain
      injury occurs despite the lack of severe bleeding, shock, and fluid
      administration. We aimed to correlate coagulation activation/inhibition, thrombin
      generation and fibrinolysis with the development of acute trauma induced
      coagulopathy (TIC) and its effects on early mortality in isolated severe
      traumatic brain injury (iSTBI) patients. METHODS: A prospective screening of
      iSTBI patients was done for two years. History of anticoagulants, liver disease,
      hypotension, extracranial injuries, transfusion, brain death were excluded. TIC
      was defined as international normalized ratio (INR) >= 1.27 and/or prothrombin
      time (PT) >= 16.7 seconds and/or activated partial thromboplastin Time (aPTT) >=
      28.8 seconds on admission following iSTBI. Analysis of tissue factor (TF), tissue
      factor pathway inhibitor (TFPI), protein C (PC), protein S (PS),
      thrombin/antithrombin complex (TAT), soluble fibrin monomer (sFM), tissue
      plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) was
      done. Cases were categorized as presence or absence of TIC and 20 healthy
      controls participants were included. RESULTS: A total of 120 cases met the
      inclusion criteria, aged 35.7 +/- 12.12 years, 96% males. TIC was identified in
      50 (41.6%). TIC occurred independently of age, sex, Glasgow coma scale (GCS) but
      was associated with acidosis (60%; p = .01). Following iSTBI significant decline
      was seen in coagulation activation. Thrombin generation and fibrinolysis were
      markedly increased. TF, TFPI, PC and PS were low in TIC compared with control.
      Significant depletion of PS was seen in TIC versus No-TIC. TBI patients with
      depleted PS had an odds ratio (OR) of 7.10 (1.61-31.2) for TIC. Receiver
      operating characteristic curve (ROC) analysis depicted area under the curve (AUC)
      of 0.73 (95% confidence interval [CI] 0.63-0.84) with a cut-off of >=74 of PS
      (specificity 63.9%, sensitivity 72.7%). In-hospital mortality was higher in TIC
      group (44%) compared with no-TIC (20%) with OR of 4.73 (95% CI 1.68-13.3) and
      hazard ratio [HR] of 2.8 (95 % CI 1.2-6.4). CONCLUSION: Incidence of TIC in iSTBI
      is 41.6%, with 4.7 times odds for mortality. Traumatic brain injury causes
      enhanced coagulation activation, inadequate inhibition, exacerbation of thrombin
      generation, and subsequent increased fibrinolysis. ROC curve analysis revealed a
      cut-off of PS <= 74 with specificity 63.8%, sensitivity 72.7% for development of
      TIC.

PMID- 30291826
TI  - Durable remission of a patient with primary cutaneous CD8+ aggressive
      epidermotropic cytotoxic T-cell lymphoma.
AB  - Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+
      PCAETL) is a rare disease characterized by aggressive clinical course and short
      survival. All available data are extracted from case reports and case series. The
      outcome is dismal and only two reported cases were cured after several lines of
      therapies including stem cell transplant. We herein present the case of a patient
      with CD8+ PCAETL who presented with rapidly progressive skin lesions and systemic
      symptoms. He was treated with aggressive multiagent chemotherapy comprising
      cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with
      high-dose methotrexate and cytarabine (hyper-CVAD). The treatment resulted in
      durable complete remission with no evidence of disease recurrence after 58 months
      of follow-up. This is the first reported case of durable remission after first
      line treatment.

PMID- 30291827
TI  - Skilled Nursing Facility Participation in Medicare's Bundled Payments for Care
      Improvement Initiative: A Retrospective Study.
AB  - OBJECTIVE: To investigate differences in facility characteristics, patient
      characteristics, and outcomes between skilled nursing facilities (SNFs) that
      participated in Medicare's voluntary Bundled Payments for Care Improvement (BPCI)
      initiative and nonparticipants, prior to BPCI. DESIGN: Retrospective, cross
      sectional comparison of BPCI participants and nonparticipants. SETTING: SNFs.
      PARTICIPANTS: All Medicare-certified SNFs (N=15,172) and their 2011-2012 episodes
      of care for chronic obstructive pulmonary disease, congestive heart failure,
      femur and hip/pelvis fracture, hip and femur procedures, lower extremity joint
      replacement, and pneumonia (N=873,739). INTERVENTIONS: Participation in a bundled
      payment program that included taking financial responsibility for care within a
      90-day episode. MAIN OUTCOME MEASURES: This study investigates the
      characteristics of bundled payment participants and their patient characteristics
      and outcomes relative to nonparticipants prior to BPCI, to understand the
      implications of a broader implementation of bundled payments. RESULTS: SNFs
      participating in BPCI were more likely to be in urban areas (80.8%-98.4% vs
      69.5%) and belong to a chain or system (73.8%-85.5% vs 55%), and were less likely
      to be located in the south (13.1%-20.2% vs 35.4%). Quality performance was
      similar or higher in most cases for SNFs participating in BPCI relative to
      nonparticipants. In addition, BPCI participants admitted higher socioeconomic
      status patients with similar clinical characteristics. Initial SNF length of stay
      was shorter and hospital readmission rates were lower for BPCI patients compared
      to nonparticipant patients. CONCLUSIONS: We found that SNFs participating in the
      second financial risk-bearing phase of BPCI represented a diversity of SNF types,
      regions, and levels of quality and the results may provide insight into a broader
      adoption of bundled payment for postacute providers.

PMID- 30291829
TI  - Spinal Emergencies in Primary Care Practice.
AB  - Atraumatic spinal emergencies often present a diagnostic and management dilemma
      for health care practitioners. Spinal epidural abscess, cauda equina syndrome,
      and spinal epidural hematoma are conditions that can insidiously present to
      outpatient medical offices, urgent care centers, and emergency departments.
      Unless a high level of clinical suspicion is maintained, these clinical entities
      may be initially misdiagnosed and mismanaged. Permanent neurologic sequela and
      even death can result if delays in appropriate treatment occur. A focused,
      critical review of 34 peer-reviewed articles was performed to identify current
      data about accurate diagnosis of spinal emergencies. This review highlights the
      key features of these 3 pathological entities with an emphasis on appropriate
      diagnostic strategy to intervene efficiently and minimize morbidity.

PMID- 30291828
TI  - Intra- and Interrater Reliability and Concurrent Validity of a New Tool for
      Assessment of Breast Cancer related Lymphedema of the Upper Extremity (CLUE).
AB  - OBJECTIVE: The goal of this study was to develop and assess intra and inter-rater
      reliability and validity of a clinical evaluation tool for breast cancer related
      lymphedema, for use in the context of outcome evaluation in clinical trials
      DESIGN: Blinded repeated measures observational study. SETTING: Outpatient
      research laboratory. PARTICIPANTS: Breast cancer survivors with and without
      lymphedema (N=71). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The
      assessment of Intraclass Correlations (ICCs) for the Breast Cancer related
      Lymphedema in the Upper Extremity (CLUE) standardized clinical evaluation tool.
      RESULTS: Intra-rater reliability for the CLUE tool was ICC: 0.88 (95% CI: 0.71,
      0.96). Inter-rater reliability for the CLUE tool was ICC: 0.90 (95% CI: 0.79,
      0.95). Concurrent validity of the CLUE score (Pearson's r) was 0.79 with
      perometric inter-limb difference, and 0.53 with the Norman Lymphedema overall
      score. CONCLUSIONS: The CLUE tool shows excellent inter- and intra-rater
      reliability. The overall CLUE score for the upper extremity also shows moderately
      strong concurrent validity with objective and subjective measures. This newly
      developed clinical, physical assessment of upper extremity lymphedema provides
      standardization and a single score that accounts for multiple constructs. Next
      steps include evaluation of sensitivity to change, which would establish
      usefulness to evaluate intervention efficacy.

PMID- 30291830
TI  - Behind the Curve: Late-Onset Axial Spondyloarthritis.

PMID- 30291831
TI  - Postmarket Experience With HeartMate 3 Left Ventricular Assist Device: 30-Day
      Outcomes From the ELEVATE Registry.
AB  - BACKGROUND: The HeartMate 3 left ventricular assist device (Abbott, Chicago, IL)
      is designed to provide circulatory support with enhanced hemocompatibility for
      patients with advanced heart failure. The purpose of this study was to compare
      the surgical outcomes between patients treated during the European Conformity
      Mark (CE Mark [CEM]) clinical trial and those treated in the postmarket era.
      METHODS: The prospective, observational, multinational ELEVATE (Evaluating the
      HeartMate 3 with Full MagLev Technology in a Post-Market Approval Setting)
      registry includes patients receiving the HeartMate 3 following CEM approval.
      Outcomes of patients in the ELEVATE registry are compared with patients in the
      CEM trial. RESULTS: Compared with the CEM trial (N = 50), the ELEVATE registry
      group (N = 463) was more severely ill, with more patients classified as INTERMACS
      (Interagency Registry for Mechanically Assisted Circulatory Support) profile 1 to
      2 (32% versus 10%; p < 0.001). The CEM trial group was younger and underwent
      fewer concomitant valve procedures. After adjustment for differences in baseline
      characteristics, the 30-day survival was comparable between the ELEVATE registry
      and CEM trial groups (95% versus 98%; p = 0.46). Length of intensive care unit
      stay was similar between the ELEVATE registry (7 days) and CEM trial (6 days)
      groups. Most adverse event rates were comparable between the 2 groups. ELEVATE
      registry patients had a lower rate of cardiac arrhythmias (13% versus 28%; p =
      0.009). With increasing experience, the implant technique has evolved to include
      more versatile approaches such as less invasive and off-pump implantation.
      CONCLUSIONS: The 30-day outcomes for ELEVATE registry patients are comparable
      despite being sicker than CEM trial patients. Adverse event rates remain low,
      with no cases of pump thrombosis within the first 30 days. Implant techniques
      have evolved to include more versatile approaches.

PMID- 30291832
TI  - Decreased PGC-1alpha Post-Cardiopulmonary Bypass Leads To Impaired Oxidative
      Stress In Diabetic Patients.
AB  - BACKGROUND: The mechanism of mitochondrial dysfunction following cardiopulmonary
      bypass (CPB) in diabetics lacks understanding. We hypothesized that impaired beta
      oxidation of fatty acids leads to worsened stress response in this patient
      population after cardiac surgery. METHODS: After IRB approval, right atrial
      tissue samples were collected from 35 diabetic and 33 non-diabetics pre- and post
      CPB. Patients with HbA1c >= 6.0 and a clinical diagnosis of diabetes mellitus
      were considered to be diabetic. Immunoblotting and microarray analysis were
      performed to assess protein and gene expression changes. Blots were quantified
      with ImageJ and analyzed using one-way ANOVA with multiple t-test comparisons
      after normalization. P-values < 0.05 were considered significant.
      Immunohistochemistry was performed for cellular lipid deposition assessment.
      RESULTS: Diabetics had significantly lower levels of PGC-1alpha pre- and post-CPB
      (p < 0.01 for both) compared to non-diabetics. Several upstream regulators of PGC
      1alpha (SIRT1 and CREB) were significantly higher in non-diabetics pre-CPB (p =
      0.01 and 0.0018, respectively). Antioxidant markers (NOX4 and GPX4), angiogenic
      factors (TGF-beta, NT3, and Ang1), and the anti-apoptotic factor Bcl-xL were
      significantly lower in diabetics post-CPB (p < 0.05). The expression of genes
      supporting mitochondrial energy production (CREB5 and SLC25A40) and angiogenic
      genes (p < 0.05) was significantly down-regulated in diabetics post-CPB.
      Immunohistochemistry results showed significantly increased lipid deposition in
      diabetic myocardial tissue. CONCLUSIONS: Decreased PGC-1alpha in diabetics may
      lead to impaired mitochondrial function and attenuated anti-apoptotic and
      angiogenic responses post-CPB. PGC-1alpha and upstream regulators could serve as
      a target for improving beta-oxidation in diabetics.

PMID- 30291833
TI  - Minimally invasive awake mitral valve surgery and cardiopulmonary bypass without
      general anesthesia.
AB  - Herein, we report the case of a 49-year-old man with a potentially fatal allergy
      to propofol and remifentanil who underwent awake minimally invasive mitral valve
      surgery with cardiopulmonary bypass using thoracic epidural anesthesia, without
      the need for endotracheal general anesthesia. The aim was the management of
      spontaneous respiration during cardiopulmonary bypass surgery in an awake
      patient.

PMID- 30291834
TI  - Postoperative Pneumonia Prevention in Pulmonary Resections: A Feasibility Pilot
      Study.
AB  - BACKGROUND: Pneumonia after pulmonary resection occurs in 5% to 12% of patients
      and causes substantial morbidity. Oral hygiene regimens lower the incidence of
      ventilator-associated pneumonias; however, the impact in patients undergoing
      elective pulmonary resection is unknown. We conducted a prospective pilot study
      to assess the feasibility of an oral hygiene intervention in this patient cohort.
      METHODS: Patients undergoing elective pulmonary resection were prospectively
      enrolled in a single-arm interventional study with time-matched controls.
      Participants were asked to brush their teeth with 0.12% chlorhexidine three times
      daily for 5 days before their operations and 5 days or until the time of
      discharge after their operations. Patients were eligible if they had known or
      suspected lung cancer and were undergoing (1) any anatomic lung resection or (2)
      a wedge resection with forced expiratory volume in 1 second or diffusing capacity
      of lung for carbon monoxide less than 50% predicted. RESULTS: Sixty-two patients
      were enrolled in the pilot intervention group and compared with a contemporaneous
      cohort of 611 patients who met surgical inclusion criteria. Preoperative
      adherence to the chlorhexidine toothbrushing regimen was high: median 100%
      (interquartile range: 87% to 100%). Postoperatively, 80% of patients continued
      toothbrushing, whereas 20% declined further participation. Among those who
      participated postoperatively, median adherence was 86% (interquartile range: 53%
      to 100%). There was a trend toward reduction in postoperative pneumonia: 1.6% (1
      of 62) in the intervention cohort versus 4.9% (30 of 611) in the time-matched
      cohort (p = 0.35). The number needed to treat to prevent one case of pneumonia
      was 30 patients. CONCLUSIONS: This pilot study demonstrated patients can comply
      with an inexpensive perioperative oral hygiene regimen that may be promising for
      reducing morbidity (Clinical Trials Registry: NCT01446874).

PMID- 30291835
TI  - Early Clinical Outcomes of Hybrid Arch Frozen Elephant Trunk Repair With the
      Thoraflex Hybrid Graft.
AB  - BACKGROUND: Hybrid aortic arch surgery has evolved to include several technical
      variations, with most including an off-label use of a conventional thoracic
      endograft. We describe the early clinical outcomes of the Thoraflex Hybrid graft
      (Vascutek, Glasgow, Scotland) specifically designed for the treatment of complex
      arch and proximal descending aortic disease. METHODS: Between January 2014 and
      April 2017, 40 consecutive patients (66 +/- 14 years of age, 45% women) underwent
      hybrid aortic arch and frozen elephant trunk repair with the multibranched
      Thoraflex Hybrid graft at 9 Canadian centers. Surgical indications included
      transverse arch or proximal descending aortic aneurysm in 100%, acute dissection
      in 10%, chronic dissection in 43%, and acute aortic rupture in 1 patient.
      Antegrade cerebral perfusion and moderate hypothermia (24.3 +/- 1.8 degrees C)
      were employed in all cases. RESULTS: All 40 device implants were successful. The
      30-day or in-hospital mortality was 5%. Stroke and transient neurological
      deficits occurred in 5% and 3% of patients, respectively. Two (5%) patients
      experienced transient spinal cord ischemia-there were no instances of permanent
      paraplegia. Mean follow-up was 550 +/- 328 days and late complications included
      type A aortic dissection in 1 patient, type B dissection in 2 patients, and
      further distal endografting in 2 patients. Survival at 30 days, 1 year, and 2
      years was 95%, 95%, and 90%, respectively. CONCLUSIONS: Hybrid aortic arch and
      frozen elephant trunk repair with the Thoraflex Hybrid graft appears to be
      associated with good clinical outcomes, despite being early in the learning curve
      with this graft. Further investigation with this device is warranted to establish
      its role within the variations of hybrid arch repair.

PMID- 30291836
TI  - Characterization of recombinant monoclonal antibody charge variants using WCX
      chromatography, icIEF and LC-MS/MS.
AB  - Charge heterogeneity is an important aspect of research into the development of
      monoclonal antibody drugs. In the present study, charge variants were separated
      into four fractions using weak cation exchange chromatography and were thoroughly
      analyzed using liquid chromatography-mass spectrometry at multiple levels.
      Molecular weight analysis of intact antibody and subunits confirmed the presence
      of heavy-chain leader sequences, light-chain leader sequences, dehydration, and
      cysteinylation. Peptide mapping of the fractions using different enzymes further
      localized the modified sites. Modified proportions identified at peptide level
      were compared with the purity detected by imaged capillary isoelectric focusing,
      the results showed that basic variant 1 consisted of cysteinylation and
      dehydration of asparagine, and basic variant 2 fully accounted for the N-terminal
      leader sequence of the heavy chain. About 14.8% of the acidic variant can be
      explained by N-terminal leader sequences in the light chain, and 18% of the
      acidic variant was demonstrated to be deamidation of asparagine in the heavy
      chain. There was approximately 54.2% of the acidic variant still cannot be
      explained. It was hypothesized that those acidic variants that have not yet been
      identified are an ensemble of molecules with slight molecular weight differences
      or the same molecular weight but different structures.

PMID- 30291837
TI  - Polymerase assays for lead discovery: An overall review of methodologies and
      approaches.
AB  - Polymerases represent an attractive molecular target for antibacterial drug
      development, antiviral intervention and cancer therapy. Over the past decade,
      academic groups and scientists from pharmaceutical industry have developed a
      large plethora of different functional assays to monitor the enzymatic reaction
      catalyzed by polymerases. These assays were used to enable high-throughput
      screening (HTS) for lead discovery purposes, as well as hit-to-lead (H2L) drug
      profiling activities. In both cases the choice of the assay technology is
      critical and to the best of our knowledge, there is no review available to help
      scientists to choose the most suitable assay. This review summarizes the most
      common functional assays developed to monitor the enzymatic activity of
      polymerases and discusses the advantages and disadvantages of each assay. Assays
      are presented and evaluated in term of cost, ease of use, high-throughput
      screening compatibility and liability towards delivering false positives and
      false negatives.

PMID- 30291838
TI  - Oligomerization and carbohydrate binding of glucan phosphatases.
AB  - Glucan phosphatases are a unique subset of the phosphatase family that bind to
      and dephosphorylate carbohydrate substrates. Family members are found in diverse
      organisms ranging from single-cell red algae to humans. The nature of their
      functional oligomerization has been a source of considerable debate. We
      demonstrate that the human laforin protein behaves aberrantly when subjected to
      Size Exclusion Chromotography (SEC) analysis due to interaction with the
      carbohydrate-based matrix. This interaction complicates the analysis of laforin
      human disease mutations. Herein, we show that SEC with Multi-Angle static Light
      Scattering (SEC-MALS) provides a method to robustly define the oligomerization
      state of laforin and laforin variants. We further analyzed glucan phosphatases
      from photosynthetic organisms to define if this interaction was characteristic of
      all glucan phosphatases. Starch EXcess-four (SEX4) from green plants was found to
      lack significant interaction with the matrix and instead exists as a monomer.
      Conversely, Cm-laforin, from red algae, exists as a monomer in solution while
      still exhibiting significant interaction with the matrix. These data demonstrate
      a range of oligomerization behaviors of members of the glucan phosphatase family,
      and establish SEC-MALS as a robust methodology to quantify and compare
      oligomerization states between different proteins and protein variants in this
      family.

PMID- 30291839
TI  - Role of bleeding recognition and evaluation in Black-White disparities in
      endometrial cancer.
AB  - BACKGROUND: Advanced stage at diagnosis is an independent, unexplained
      contributor to racial disparity in endometrial cancer. OBJECTIVE: We sought to
      investigate whether, prior to diagnosis, provider recognition of the cardinal
      symptom of endometrial cancer, postmenopausal bleeding, differs by patient race.
      STUDY DESIGN: Black and White women diagnosed with endometrial cancer (2001
      through 2011) from Surveillance, Epidemiology, and End Results-Medicare who had
      at least 2 years of claims prior to diagnosis were identified. Bleeding diagnoses
      along with procedures done prior to diagnosis were captured via claims data.
      Multinomial logistic regression was used to evaluate the association of race with
      diagnostic workup and multivariate models built to determine the association of
      appropriate diagnostic procedures with stage at diagnosis. RESULTS: In all, 4354
      White and 537 Black women diagnosed with endometrial cancer were included.
      Compared to White women, Black women were less likely to have guideline
      concordant care: postmenopausal bleeding and appropriate diagnostic evaluation
      (70% vs 79%, P < .001), with adjusted relative risk ratios of 1.12-1.73 for
      different nonguideline-concordant pathways: bleeding without diagnostic
      procedures, alternative bleeding descriptions, and neither bleeding nor
      procedures. These pathways were associated with higher odds of advanced stage at
      diagnosis (adjusted odds ratio, 1.90-2.88). CONCLUSION: The lack of recognition
      and evaluation of postmenopausal bleeding is associated with advanced stage at
      diagnosis in endometrial cancer. Older Black women are at highest risk for the
      most aggressive histology types, yet they are less likely to have guideline
      concordant evaluation of vaginal bleeding. Efforts aimed at improving recognition
      among patients and providers-of postmenopausal bleeding in Black women could
      substantially reduce disparities in endometrial cancer.

PMID- 30291840
TI  - A US population-based study of uterine fibroid diagnosis incidence, trends, and
      prevalence: 2005 through 2014.
AB  - BACKGROUND: Despite considerable public health burden, uterine fibroid population
      based incidence estimates are few. Secular trends over time are even more
      limited. OBJECTIVE: We sought to evaluate the incidence, 10-year secular trends,
      and prevalence of uterine fibroid diagnoses and describe the proportion of
      symptomatic women. STUDY DESIGN: We performed a retrospective population-based
      cohort study of women, aged 18-65 years, enrolled 2005 through 2014 in Kaiser
      Permanente Washington. Uterine fibroid diagnoses identified by International
      Classification of Diseases, Ninth Revision codes and potential covariates were
      extracted from computerized databases. Women with prior hysterectomy and, for
      incidence estimates, women with prior fibroid diagnoses were excluded. Linear
      trends in incidence rates over the 10-year study period were evaluated using
      Poisson regression models. Rates and trend tests were examined for all women, by
      age groups, and by race/ethnicity. RESULTS: Associated International
      Classification of Diseases, Ninth Revision symptom-related codes were observed in
      90% of incident cases. Incidence rates for fibroid diagnoses were highest for the
      age group 45-49 years, 240.3 per 10,000 woman-years in 2014, and for black women
      across all years. Overall age-adjusted estimated incidence rates declined during
      the 10-year study interval, from 139.4 per 10,000 woman-years in 2005 to 101.4 in
      2014 (P value trend .0008). Overall prevalence in 2014 was 9.6%, and was highest
      among women aged 50-54 years (15.9%). Black women had higher prevalence (18.5%)
      than other racial/ethnic groups. CONCLUSION: We found a decreasing trend of new
      uterine fibroid diagnoses among predominantly symptomatic women ages 18-65 years
      in a recent 10-year interval. This finding was due, perhaps in part, to secular
      trends of decreasing hysterectomies. Nonetheless, uterine fibroids remain a
      common health burden, with a prevalence of nearly 10%. Rates are
      disproportionately high and occur at younger ages for black women, and possibly
      for other non-white racial/ethnic groups. These findings are of concern, as
      current available long-term medical therapies remain limited.

PMID- 30291841
TI  - A first step to improving maternal mortality in a low-literacy setting; the
      successful use of singing to improve knowledge regarding antenatal care.
AB  - BACKGROUND: Preventable maternal mortality is related to delays in recognizing
      the problem, transport to a facility, and receiving appropriate care on arrival.
      Reducing maternal mortality in low-literacy settings is particularly challenging.
      In the rural villages of Nepal, the maternal mortality rate is among the highest
      in the world; the reasons include illiteracy and lack of knowledge of the needs
      of pregnant women. Culturally, singing and dancing are part of Nepalese daily
      life and present an opportunity to transmit knowledge of antenatal care and care
      at birth with a view to reducing the first 2 delays. OBJECTIVE: We hypothesized
      that health messages regarding the importance of antenatal care and skilled birth
      assistance would be effectively transmitted by songs in the limited literacy
      environment of rural Nepal. STUDY DESIGN: We randomly grouped 4 rural village
      development committees comprising 36 villages into 2 (intervention and control)
      clusters. In the intervention group, local groups were invited to write song
      lyrics incorporating key health messages regarding antenatal care to accompany
      popular melodies. The groups presented their songs and dances in a festival
      organized and judged by the community. The winning songs were performed by the
      local people in a song and dance progression through the villages, houses, and
      fields. A wall chart with the key health messages was also provided to each
      household. Knowledge of household decision makers (senior men and women) was
      assessed before and after the intervention and at 12 months using a structured
      questionnaire in all households that also assessed behavior change. RESULTS:
      Structured interviews were conducted at baseline, immediately postintervention in
      the control and intervention areas (intervention n = 735 interviews, control n =
      775), and at 12 months in the intervention area only (n = 867). Knowledge scores
      were recorded as the number of correct items out of 36 questions at baseline and
      postintervention, and of 21 questions at follow-up. Postintervention, test score
      doubled in the intervention group from a mean of 11.60/36-22.33/36 (P < .001),
      with no practically significant change in the control population (17.48/36
      18.26/36). Improvement was greatest among the most illiterate members of the
      community (6.8/36-19.8/36, P < .001). At 12 months follow-up, a majority of the
      participants (63.9%) indicated that they provided information learned from the
      songs to their neighbors and friends, and 41.3% reported still singing the songs
      from the intervention. CONCLUSION: The use of songs bypassed the limitations of
      literacy in communicating health messages that are key to improving maternal care
      in this low-literacy rural setting within a developing country. The improvements
      were maintained without further intervention for 12 months. With appropriate
      sociocultural adaptation to local contexts, this low-cost method of community
      education may be applicable to improving maternal health knowledge and behavior
      change in other low-resource and limited literacy settings that may lead to
      reductions in maternal mortality.

PMID- 30291842
TI  - Epidemiology and risk factors of asthma-chronic obstructive pulmonary disease
      overlap in low- and middle-income countries.
AB  - BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO)
      represents the confluence of bronchial airway hyperreactivity and chronic airflow
      limitation and has been described as leading to worse lung function and quality
      of life than found with either singular disease process. OBJECTIVE: We aimed to
      describe the prevalence and risk factors for ACO among adults across 6 low- and
      middle-income countries (LMICs). METHODS: We compiled cross-sectional data for
      11,923 participants aged 35 to 92 years from 4 population-based studies in 12
      settings. We defined COPD as postbronchodilator FEV1/forced vital capacity ratio
      below the lower limit of normal, asthma as wheeze or medication use in 12 months
      or self-reported physician diagnosis, and ACO as having both. RESULTS: The
      prevalence of ACO was 3.8% (0% in rural Puno, Peru, to 7.8% in Matlab,
      Bangladesh). The odds of having ACO were higher with household exposure to
      biomass fuel smoke (odds ratio [OR], 1.48; 95% CI, 0.98-2.23), smoking tobacco
      (OR, 1.28 per 10 pack-years; 95% CI, 1.22-1.34), and having primary or less
      education (OR, 1.35; 95% CI, 1.07-1.70) as compared to nonobstructed nonasthma
      individuals. ACO was associated with severe obstruction (FEV1 %, <50; 31.6% of
      ACO vs 10.9% of COPD alone) and severe spirometric deficits compared with
      participants with asthma (-1.61 z scores FEV1; 95% CI, -1.48 to -1.75) or COPD
      alone (-0.94 z scores; 95% CI, -0.78 to -1.10). CONCLUSIONS: ACO may be as
      prevalent and more severe in LMICs than has been reported in high-income
      settings. Exposure to biomass fuel smoke may be an overlooked risk factor, and we
      favor diagnostic criteria for ACO that include environmental exposures common to
      LMICs.

PMID- 30291843
TI  - Loss of Sfrp2 contributes to the neurological disorders related with morphine
      withdrawal via Wnt/beta-catenin signaling.
AB  - Morphine administration is a medical problem characterized by compulsive opioid
      use that causes terrible negative consequences. The exact mechanisms of morphine
      induced dependence and morphine withdrawal symptoms remain unclear. Recent
      studies have revealed that the upregulation of Wnt/beta-catenin signaling plays
      important roles in morphine exposure and morphine withdrawal. Secreted frizzled
      related protein 2 (Sfrp2) can prevent the activation of Wnt/beta-catenin
      signaling by competing with the Frizzled receptor for Wnt ligands. We conducted
      this study aimed to evaluate the effect of iatrogenic trauma induced by
      stereotactic surgery and the protective effect of stereotaxic Sfrp2 injection on
      morphine withdrawal symptoms in Male Sprague Dawley (SD) rats. Many techniques
      including western blot analysis and immunoprecipitation were used. Anxiety
      related behaviors, morphine withdrawal syndrome, and dendritic spines were also
      examined in male SD rats after morphine treatment and stereotaxic injection of
      Sfrp2. Western blot results suggested that Wnt signaling was activated in the
      nucleus accumbens of SD rats suffering from morphine withdrawal and that Sfrp2
      attenuated the overexpression of Wnt signaling. Similarly, the withdrawal-like
      symptoms of morphine dependent rats were abrogated by intracerebral Sfrp2
      injection. The iatrogenic trauma induced by stereotactic surgery showed no
      influence on the Wnt signaling and withdrawal-like symptoms. Moreover, the
      results of Golgi-cox staining and DiI staining indicated that the damage on
      proximal spine density caused by morphine treatment was restored by intracerebral
      Sfrp2 injection. Together, the data presented here indicated that Sfrp2 abrogated
      the neurological disorders and loss of proximal spine related with morphine
      withdrawal via Wnt/beta-catenin signaling.

PMID- 30291844
TI  - Immunoinformatics and molecular docking studies reveal potential epitope-based
      peptide vaccine against DENV-NS3 protein.
AB  - Dengue, still a "Neglected Tropical Disease" is somehow injustice and remains
      uncontrolled globally. World Health Organization (2012-2020) reported that the
      world's half population is living in dengue-affected regions. Therefore,
      effective drug candidates or promising vaccines are urgently needed to control
      the dengue. It is an acute febrile disease caused by mosquito borne dengue
      viruses (DENVs) which belong to the genus Flavivirus with four serotypes. In
      present work, immunoinformatics approach was utilized to predict the antigenic
      epitopes of dengue proteins for the development of DENV vaccine. B-cell and
      cytotoxic T-lymphocyte epitopes were predicted for NS3 dengue protein. Docking
      complexes of 17 antigenic B-cell epitopes of various lengths and 4 CTL epitopes
      with antigenic sites were investigated followed by binding interaction analyses
      of top predicted peptides with MHC-I HLA-A2 molecule. These predicted epitopes
      with antigenic amino acids might present a preliminary set of peptides for future
      vaccine development against DENV.

PMID- 30291845
TI  - Conformational states of Zika virus non-structural protein 3 determined by
      molecular dynamics simulations with small-angle X-Ray scattering data.
AB  - Zika virus (ZIKV) has become a great public health emergency. Its non-structural
      protein 3 (NS3) is a key enzyme in viral replication and has been considered as a
      potential therapeutic target. A conformational characterization of ZIKV NS3 is
      critical for a comprehensive understanding of its molecular interactions and
      functions. However, the high conformational flexibility of solution NS3 obstacles
      the structural characterization of NS3 solely from the experimental observable
      that averages over its heterogeneous conformations. Here, we employed replica
      exchange with solute tempering (REST) method to simulate the di-domain protein
      ZIKV NS3. Three independent MD simulations identified a conserved conformational
      ensemble of NS3, consisting of a major conformational state and several minor
      states from compact to loose conformations. The major state agrees well with the
      scattering profile from small-angle X-ray scattering (SAXS) experiments.
      Moreover, the simulated ensemble is supported by a direct data-fitting result
      that requires both short- and long-range structural contacts to recover the
      experimental data. We discussed the interplay between simulation and experiment
      in ensemble construction of flexible biomolecules and shed light on the
      physically derived conformational ensembles.

PMID- 30291846
TI  - Overexpression of Desmoglein 2 in a mouse model of Gorlin syndrome enhances
      spontaneous basal cell carcinoma formation through STAT3-mediated Gli1
      expression.
AB  - Activation of the Hedgehog (Hh) pathway is causative of virtually all sporadic
      and Gorlin syndrome-related basal cell carcinomas (BCC), with loss of function of
      Patched1 (Ptc1) being the most common genomic lesion. Sporadic BCCs also
      overexpress desmoglein-2 (Dsg2), a desmosomal cadherin normally found in the
      basal layer. Using a mouse model of Gorlin syndrome (Ptc1+/lacZ mice), we found
      that overexpressing Dsg2 in the basal layer (K14-Dsg2/Ptc1+/lacZ) or the
      superficial epidermis (Inv-Dsg2/Ptc1+/lacZ mice) resulted in increased
      spontaneous BCC formation at 3 and 6 months, respectively. The tumors did not
      show loss of heterozygosity of Ptc1, despite high levels of Gli1 and
      phosphorylated Stat3. A panel of sporadic human BCCs showed increased staining of
      both Dsg2 and P-Stat3 in 9/9 samples. Overexpression of Dsg2 in ASZ001 cells, a
      Ptc1-/- BCC cell line, induced Stat3 phosphorylation and further increased Gli1
      levels, both in an autocrine and paracrine manner. Three different Stat3
      inhibitors reduced viability and Gli1 expression in ASZ001 cells, but not in
      HaCaT cells. Conversely, stimulation of Stat3 in ASZ001 cells with IL-6 increased
      Gli1 expression. Our results indicate that Dsg2 enhances canonical Hh signaling
      downstream of Ptc1 to promote BCC development through the activation of P-Stat3
      and regulation of Gli1 expression.

PMID- 30291847
TI  - Implementation of a reformulated Roche(r) bilirubin Gen.3 reagent did not affect
      the relationship between BiliChek transcutaneous and Roche total serum bilirubin.
AB  - OBJECTIVE: Determine whether introduction of a reformulated bilirubin reagent,
      the Roche bilirubin Gen.3 assay, changed the relationship between BiliChek
      transcutaneous bilirubin (TcB) and total serum bilirubin (TSB). DESIGN AND
      METHODS: TcB results from term infants in the level 1 nursery obtained within one
      hour of a TSB were reviewed over two periods, six months before and after the
      conversion from the previous generation Roche bilirubin reagent to the new Roche
      Gen.3 bilirubin assay. TcB measurements were performed using BiliChek
      transcutaneous devices (Respironics, Marietta GA). Distribution of TSB results,
      and TcB minus TSB bias, were compared before and after introduction of the
      reformulated Roche bilirubin Gen.3 assay. Median and interquartile range (IQR)
      TSB values and bias were calculated. A statistical difference between median TSB
      values and bias were assessed using Man-Whitney test. RESULTS: A total of 301
      paired TcB and TSB results were obtained, 172 before and 129 after implementation
      of the reformulated Roche bilirubin Gen.3 reagent. Median (IQR) TSB was 7.8 (6.8
      8.7)mg/dL (133.3 (116.3-148.8) MUmol/L) before and 7.6 (6.7-8.4)mg/dL (130 (114.6
      143.6)MUmol/L) after implementation of the reformulated reagent (p = .1373).
      Median (IQR) bias between TcB and TSB was 2.9 (2.2-3.7) mg/dL (49.6 (37.6
      63.3)MUmol/L) before the reformulated reagent was implemented; and did not change
      at 2.9 (2.1-3.9) mg/dL (49.6 (35.9-66.7)MUmol/L) after implementation (p =
      .8242). CONCLUSION: Implementation of the reformulated Roche bilirubin Gen.3
      reagent did not affect the relationship between BiliChek transcutaneous and total
      serum bilirubin; thus no changes were needed to the neonatal TcB screening
      protocol as a result of the new bilirubin reagent.

PMID- 30291848
TI  - Traceability of immunosuppressant's mass concentration results obtained using
      different commercial calibrators.
AB  - BACKGROUND: Due to the high inter-variability in immunosuppressants
      pharmacokinetics, therapeutic drug monitoring of these drugs is essential in
      order to minimize the risk of rejection after organ transplantation. Thus,
      results facilitated to clinicians by clinical laboratories for these drugs should
      be as reliable as possible. The knowledge of metrological traceability and
      performing compatibility studies can allow ensuring reliability of these results,
      mainly, when laboratories introduce substantial changes in their measurement
      procedures, e.g., when they change the calibration materials. The aim of this
      study was to investigate, as an example, the traceability of the calibrator's
      assigned values from two manufacturers (Recipe and Chromsystems) and to perform
      compatibility studies for sirolimus and tacrolimus. MATERIAL AND METHODS:
      Traceability was described according to ISO 17511. Compatibility studies, based
      on the CLSI EP029-A guideline, were performed verifying the trueness processing
      the ERM(r)-DA111a and ERM(r)-DA110a reference materials. RESULTS: Traceability
      studies reveled that sirolimus and tacrolimus results were traceable to SI,
      except for sirolimus if Chromsystems' calibrators was used. Using Recipe's
      calibrators, the absolute relative biases and their expanded uncertainties were
      1.23% and +/-6.10% for sirolimus, and 1.41% and +/-3.02% for tacrolimus.
      Furthermore, when Chromsystems' calibrators were used, these values were 12.2%
      and +/-6.02% for sirolimus, and 2.64% and +/-2.94% for tacrolimus. CONCLUSIONS:
      Results reported a lack of traceability and compatibility of sirolimus' results
      when Chromsystems' calibrators was used. In order to avoid it, laboratories
      should only use calibrators with assigned values traceable to highest reference
      materials or, alternatively, perform a compatibility study and apply a bias
      correction factor.

PMID- 30291849
TI  - Virtual chromoendoscopy using optical enhancement improves the detection of
      Barrett's esophagus-associated neoplasia.
AB  - BACKGROUND AND AIMS: The Seattle protocol for endoscopic Barrett's esophagus
      surveillance samples a small proportion of the mucosal surface area - risking a
      potentially high miss rate of early neoplastic lesions. We assess if the new
      iScan Optical Enhancement system (OE, Pentax) improves the detection of early BE
      associated neoplasia compared with high definition white light endoscopy (HD-WLE)
      in both expert and trainee endoscopists to target sampling of suspicious areas.
      Such a system may both improve early neoplasia detection and reduce the need for
      random biopsies. METHODS: 41 patients undergoing endoscopic BE surveillance from
      Jan 2016-Nov 2017 were recruited from 3 international referral centers. Matched
      still images in both HD-WLE (n=130) and iScan OE (n=132) were obtained from
      endoscopic examinations. Two experts, unblinded to the videos and histology,
      delineated known neoplasia, forming a consensus criterion standard. 7 expert and
      7 trainee endoscopists marked one position per image where they would expect a
      target biopsy to identify dysplastic tissue. The same expert panel then reviewed
      magnification images and using a previously validated classification system
      attempted to classify mucosa as dysplastic or non-dysplastic based on the mucosal
      and vascular patterns observed on magnification endoscopy. Diagnostic accuracy,
      sensitivity, specificity, NPV, and PPV were calculated. Improvements in dysplasia
      detection in HD-WLE vs OE and interobserver agreement (IA) were assessed by
      multilevel logistic regression analysis and Krippendorff's alpha, respectively.
      Improvements in diagnostic performance were expressed as an odds ratio between
      the odds of an improvement in OE, compared with the odds of an improvement in WLE
      RESULTS: Accuracy of neoplasia detection was significantly higher in all trainees
      using OE versus WLE (76% vs 63%) and in 6 experts (84% vs 77%). OE improved
      sensitivity of dysplasia detection compared with WLE in 6 trainees (81% vs 71%)
      and 5 experts (77% vs 67%). Specificity improved in 6 trainees using OE vs WLE
      (70% vs 55%) and in 5 experts (92% vs 86%). PPV improved in both an expert and
      trainee cohort but NPV only improved significantly in trainees. Using the MV
      classification and OE magnification endoscopy compared with HD-WLE, we
      demonstrated improvements in accuracy (79.9% vs 66.7%), sensitivity (86.3% vs
      83.4%) and specificity (71.2% vs 53.6%) of dysplasia detection. PPV improved (62%
      to 76.6%), as did NPV (67.7% to 78.5%).Interobserver agreement also improved
      using OE from 0.30 to 0.55. CONCLUSION: iScan OE may improve dysplasia detection
      on endoscopic imaging of BE, as well as the accuracy of histology prediction
      compared with HD-WLE, when using OE magnification endoscopy in conjunction with a
      simple classification system in both expert and non-expert endoscopists.

PMID- 30291850
TI  - Muscle damage and inflammation biomarkers after two ultra-endurance mountain
      races of different distances: 54 km vs 111 km.
AB  - The aims of this study were 1) to describe the effects of a 54 km and 111 km
      ultra-endurance mountain race on the biomarkers of muscle damage and
      inflammation, 2) to compare the effects between the two races regarding the
      biomarkers of muscle damage and inflammation. Sixteen ultra-endurance amateur
      runners volunteered to participate in this study. Ten runners completed a 54 km
      race (Group 1; age: 27.0 +/- 5.7; height: 179.5 +/- 5.8 cm; and body mass: 77.3
      +/- 10.7 kg) and six completed a 111 km race (Group 2; age: 30.5 +/- 8.0; height:
      179.4 +/- 5.5 cm; and body mass: 76.2 +/- 9.4 kg). Blood samples were taken at
      five different points during the investigation, 24 h before the race, immediately
      post-race, and again at 24, 48, and 72 h after the race. There were increases in
      leukocyte (Group 1: p <= .001, ES = 2.8; Group 2: p = .001, ES = 3.5) and
      platelet concentrations (Group 1: p <= .001, ES = 2.3; Group 2: p = .02, ES =
      1.7) post-races. Significant inter-race differences were also observed in
      leukocyte at 72 h (Group 1: 5.5 +/- 0.9, Group 2: 4.2 +/- 0.9, p = .012, ES =
      1.5). Erythrocytes, hematocrit and hemoglobin concentration decreased after 54 km
      and 111 km races at 24, 48 and 72 h (p <=.001, ES = 2.0-3.18). Serum uric acid
      concentration increased after the 54 km race (pre = 4.9 +/- 1.2 - post = 7.3 +/-
      1.0 8 mg/dl; p <= .001, ES = 2.4), and also the 111 km race (pre = 5.3 +/- 0.9 -
      post = 6.7 +/- 0.8 mg/dl; p < .008, ES = 2.2). GPT, GOT and LDH had changed by
      the end of the races (p < .05) and differences between the groups were observed
      in GOT post-race (p = .008, ES = 1.7) 24 h (p = .004, ES = 1.8), 48 h (p = .007,
      ES = 1.6), and 72 h (p = .02, ES = 1.4) and also in LDH at 24, 48, 72 h. Serum
      creatinine decreased post-race in Group 1 (pre = 1.1 +/- 0.1 - post = 1.4 +/- 0.2
      mg/dl; p = .001, ES = 1.5) and Group 2 (pre = 1.2 +/- 0.1, post = 1.5 +/- 0.2; p
      = .002, ES = 3.3) along with CK and myoglobin. In addition, values did not return
      to baseline levels after 72 h in Group 2 for C-reactive protein, myoglobin, and
      CK. Differences between the races were also observed post-race in Troponin I
      (Group 1 = 0.06 +/- 0.05, 111 km = 0.02 +/- 0.01 MUg/l, p = .047, ES = 1.1) and C
      reactive protein post-race (Group 2 = 2.5 +/- 1.6, 111 km = 18.2 +/- 6.4 mg/l, p
      <= .001, ES = 4.4) at 24 and 48 h. The athletes had increased concentrations of
      markers associated with damage, inflammation, muscle injury and cardiac damage
      after the races. Furthermore, athletes who completed the greater distance (111
      km) had higher concentrations of the markers associated with muscle damage and
      muscle inflammation which remained changed for a period of 72 h. However, the
      participants of the 'shorter race' showed higher values associated with cardiac
      damage. Consequently, athletes who take part in these kinds of races should wait
      at least 72 h before training with high load.

PMID- 30291851
TI  - A Simple and Noninvasive DOSY NMR Method for Droplet Size Measurement of Intact
      Oil-In-Water Emulsion Drug Products.
AB  - In a typical oil-in-water emulsion drug product, oil droplets with varied sizes
      are dispersed in a water phase and stabilized by surfactant molecules. The size
      and polydispersity of oil droplets are critical quality attributes of the
      emulsion drug product that can potentially affect drug bioavailability. More
      critically, to ensure accuracy in characterization of the finished drug product,
      analytical methods should introduce minimal physical perturbation (e.g.,
      temperature variation or dilution) before the analysis. The classical methods of
      dynamic light scattering or electron microscopy can be used but they generally
      require sample dilution or harsh preparation conditions, respectively. By
      contrast, the size distribution of emulsion formulations can be assessed with a
      simple and noninvasive solution nuclear magnetic resonance method, viz. two
      dimensional Diffusion Ordered SpectroscopY. The two-dimensional Diffusion Ordered
      SpectroscopY method probed signal decay of methyl resonances from oil and sorbate
      molecules and was applied to three types of U.S.-marketed emulsion drug products,
      that is, difluprednate, cyclosporine, and propofol, yielding measured droplet
      sizes of 40-280 nm in diameter. The high precision of +/-6 nm of the new nuclear
      magnetic resonance method allows analytical differentiation of lot-to-lot and
      brand-to-brand droplet size differences in emulsion drug products, critical for
      drug-quality development, control, and surveillance.

PMID- 30291852
TI  - The effects of exercise on cognition and gait in Parkinson's disease: A scoping
      review.
AB  - Cognitive and gait deficits are two debilitating symptoms that occur in
      Parkinson's disease (PD). Importantly, a relationship between cognitive and gait
      deficits exists in PD, suggesting reliance on cognition is increased to
      compensate for gait deficits and/or deterioration of cognition and gait may share
      common mechanisms. Rehabilitation strategies targeting one factor could lead to
      the improvement of the other, presenting a unique opportunity to treat both
      simultaneously. Gold-standard pharmaceuticals partially alleviate these deficits
      with significant side effects, highlighting the importance of investigating
      adjunct therapies like exercise. We critically reviewed the influence of three
      exercise modalities (aerobic, resistance, and goal-based) on cognition and/or
      gait in PD. Most studies showed improvements in cognition or gait, yet, a limited
      number investigated them concurrently. This is the first review examining
      exercise for cognition and gait in PD. Key gaps in the literature are identified;
      potential exercise-driven mechanisms for enhancements in cognition and gait
      proposed, and suggestions for the design of future studies investigating the
      effects of exercise on cognition and gait in PD.

PMID- 30291853
TI  - A Mesenchymal stem cell line (B10) increases angiogenesis in a rat MCAO model.
AB  - A human mesenchymal stem cell line (B10) transplantation has been shown to
      improve ischemia-induced neurological deficits in animal stroke models. To
      understand the underlying mechanism, we have investigated the effects of B10
      transplantation on cerebral angiogenesis in a rat middle cerebral artery
      occlusion (MCAO) model. B10 cells were transplanted intravenously 24 h after
      MCAO. Immunofluorescence staining results showed that compared to PBS-groups, vWF
      positive vessel and endoglin positive new vessels were increased in B10
      transplanted MCAO groups in the lesion areas. The mRNA of angiogenesis factors
      including placental growth factor and hypoxia inducible factor (HIF)-1alpha were
      increased 3 days after MCAO in the core and IBZ areas of B10-transplanted group.
      Angiopoetin1 mRNA was increased only in the IBZ. Western blotting results showed
      that HIF-1alpha and vascular endothelial growth factor (VEGF) proteins were
      increased in B10-transplanted group. Both HIF-1alpha and VEGF were expressed in
      macrophage/microglia in the core area. In the IBZ, however, HIF-1alpha was
      expressed both in astrocytes and macrophage/microglia, while VEGF was expressed
      only in macrophage/microglia. Moreover, TGFbeta protein levels were found to be
      increased in B10-transplanted group in the core and IBZ regions. Cell culture
      experiments using a human microglia cell line (HMO6) and B10 showed that IL-1beta
      induced VEGF mRNA expression in both cell types. IL-1beta was found to be highly
      expressed in B10 cells, and its co-culture with HMO6 further increased that in
      B10. Co-culture increased VEGF mRNA in both B10 and HMO6. In the rat brains, IL
      1beta was expressed in macrophage/microglia and transplanted-B10 cells in the
      core. IL-1beta positive cell number was increased slightly, but significantly in
      B10-transplanted rats. To explore further, IL-1beta expression was silenced in
      B10 cells by transfecting mRNA specific siRNA, and then transplanted in MCAO
      rats. Immunostaining result showed that endoglin positive area was decreased in
      IL-1beta-silenced B10 transplanted groups compared to nonsilenced-B10
      transplanted groups. Interestingly, vessel-like structure appeared as early as 3
      days after MCAO in IL-1beta-silenced B10-transplanted group. Thus our results
      demonstrated that B10 cells increased angiogenesis in MCAO rat model, through the
      regulation of HIF-1alpha and VEGF expression, where IL-1beta might play a role.

PMID- 30291854
TI  - Matrices, scaffolds & carriers for cell delivery in nerve regeneration.
AB  - Nerve injuries can be life-long debilitating traumas that severely impact
      patients' quality of life. While many acellular neural scaffolds have been
      developed to aid the process of nerve regeneration, complete functional recovery
      is still very difficult to achieve, especially for long-gap peripheral nerve
      injury and most cases of spinal cord injury. Cell-based therapies have shown many
      promising results for improving nerve regeneration. With recent advances in
      neural tissue engineering, the integration of biomaterial scaffolds and cell
      transplantation are emerging as a more promising approach to enhance nerve
      regeneration. This review provides an overview of important considerations for
      designing cell-carrier biomaterial scaffolds. It also discusses current
      biomaterials used for scaffolds that provide permissive and instructive
      microenvironments for improved cell transplantation.

PMID- 30291855
TI  - Association of STAT4, TGFbeta1, SH2B3 and PTPN22 polymorphisms with autoimmune
      hepatitis.
AB  - : The physiopathology of autoimmune hepatitis (AIH) is complex and still not
      fully elucidated. The genes localized outside the histocompatibility complex
      involved in regulation and signal transduction of the immune system SH2B3,
      TGFbeta1, STAT4 and PTPN22 could be associated to the susceptibility and
      hepatocyte lysis mechanism of this lethal autoimmune disorder. PATIENTS AND
      METHODS: We investigated four polymorphic sites in SH2B3 (rs3184504), TGFbeta1
      (rs1800471), STAT4 (rs7574865) and PTPN22 (rs2476601) in 45 AIH patients and 150
      healthy controls from Tunisia using real-time PCR. RESULTS: Significant
      associations were found for SH2B3 T allele (OR = 1.861; p = 0.015, pc = 0.366)
      and PTPN22 A allele (OR = 7.070; p = 0.026; pc = 1.00) and AIH with opposite
      homozygous being protective against the disease (CC genotype with OR = 0.420, p =
      0.025; GG genotype with OR = 0.136, p = 0.025, respectively). No statistically
      significant associations were found for the TGFbeta1 and STAT4 polymorphisms with
      AIH susceptibility. CONCLUSION: Our work enlarges information on non-HLA genes
      that are associated with AIH by focusing in a region of the world that was poorly
      molecularly characterized for this disease.

PMID- 30291856
TI  - State of the art in Stratum Corneum research: The biophysical properties of
      ceramides.
AB  - This review is summarizing an important part of the state of the art in stratum
      corneum research. A complete overview on discoveries about the general
      biophysical and physicochemical properties of the known ceramide species' is
      provided. The ceramides are one of the three major components of the lipid matrix
      and mainly govern its properties and structure. They are shown to exhibit very
      little redundancy, despite the minor differences in their chemical structure. The
      results are discussed, compared to each other as well as the current base of
      knowledge. New interesting aspects and concepts are concluded or suggested. A
      novel interpretation of the 3-dimensional structure of the lipid matrix and its
      influence on the barrier function will be discussed. The most important
      conclusion is the presentation of a new and up to date theoretical model of the
      nanostructure of the short periodicity phase. The model suggests three
      perpendicular layers: The rigid head group region, the rigid chain region and, a
      liquid-like overlapping middle layer. The general principle of the skin barrier
      function is highlighted in regard to this structure and the ceramides biophysical
      and physicochemical properties. As a result of these considerations, the entropy
      vs. enthalpy principle is introduced, shedding light on the function as well as
      the effectiveness of the skin barrier. Additionally, general ideas to effectively
      overcome this barrier principle for dermal and transdermal delivery of actives or
      how to use it for specific targeting of the stratum corneum are proposed.

PMID- 30291857
TI  - A simple SI-type model for HIV/AIDS with media and self-imposed psychological
      fear.
AB  - Infectious diseases can have a large impact on society, as they cause morbidity,
      mortality, unemployment, inequality and other adverse effects. Mathematical
      models are invaluable tools in understanding and describing disease dynamics with
      preventive measures for controlling the disease. The roles of media coverage and
      behavioral changes due to externally imposed factors on the disease dynamics are
      well studied. However, the effect of self-imposed psychological fear on the
      disease transmission has not been considered in extant research, and this gap is
      addressed in the present investigation. We propose a simple SI-type model for
      HIV/AIDS to assess the effects of media and self-imposed psychological fear on
      the disease dynamics. Local and global dynamics of the system are studied. Global
      sensitivity analysis is performed to identify the most influential parameters
      that have significant impact on the basic reproduction number. After calibrating
      our model using HIV case data-sets for Uganda and Tanzania, we calculate the
      basic reproduction numbers in the study period using the estimated parameters.
      Furthermore, a comparison of the effects of awareness and self-imposed
      psychological fear effects reveals that awareness is more effective in
      eliminating the burden of HIV infection.

PMID- 30291858
TI  - Metabolic responses of brown planthoppers to IR56 resistant rice cultivar
      containing multiple resistance genes.
AB  - The brown planthopper (Nilaparvata lugens Stal, BPH) is one of the most
      destructive pests in rice production, and rice resistance is thought to be an
      economical and environmentally friendly strategy against BPH. Although resistant
      rice cultivars have been widely applied to control BPH, little is known regarding
      the impact of the ingestion of resistant plant phloem on the BPH physiological
      metabolism. In this study, the differences in the metabolic responses of BPH
      nymphs during the first 72 h after ingesting susceptible TN1 and resistant IR56
      plant phloem were compared. The results showed that BPH nymphs feeding on IR56
      plants exhibited significant decreases in honeydew excretion and body weight, and
      significantly lower concentrations of most of the detected sugars, vitamins and
      some essential amino acids but higher levels of most amides, free fatty acids and
      some non-essential amino acids. These findings indicate that the energy
      metabolism and nutrition supply of these nymphs were disturbed by the resistant
      rice plants. The qPCR results revealed that BPH could actively adapt to IR56
      plants by upregulating the gene expression levels of some detoxification enzymes,
      including GST, CarE and POD, to some extent. These results provide additional
      information to improve our understanding of physiological mechanism underlying
      the loss of BPH fitness caused by resistant rice varieties.

PMID- 30291859
TI  - A new interpretation of the mechanism underlying visual anomalies of astronauts.

PMID- 30291860
TI  - Early monocular enucleation selectively disrupts neural development of face
      perception in the occipital face area.
AB  - : Retinoblastoma generally occurs before 5 years of age and often requires
      enucleation (surgical removal of one eye) of the cancerous eye. We have
      previously shown using behavioural methods that this disruption in binocular
      vision during the critical period of visual development results in impaired face
      perception. In this case series study, we sought to determine the underlying
      neural correlates of this face perception deficit by examining brain activity in
      regions of cortex that preferentially respond to visual images of faces and
      places in 6 adults who had one eye enucleated early in life due to
      retinoblastoma. A group of 10 binocularly-intact adult controls were recruited
      for comparison. Functional magnetic resonance imaging (fMRI) was conducted over
      two separate runs for each participant in one scanning session. Each run
      consisted of 6 blocks each of face, place, and object images. Region-of-interest
      analyses were conducted to locate face-preferential [fusiform face area (FFA),
      occipital face area (OFA)] and place-preferential [parahippocampal place area
      (PPA), transverse occipital sulcus (TOS)] regions-of-interest. Descriptive
      statistics are reported. RESULTS: Enucleated adults exhibited reduced functional
      activation in face-preferential regions (left FFA, right OFA, left OFA), but
      similar activation within the face-preferential right FFA and the place
      preferential regions (bilateral PPA and TOS). CONCLUSIONS: These results indicate
      that early monocular enucleation prevents robust development of late-maturing
      face processing capabilities and that this disruption is specific to face
      networks and not to networks supporting other visual image categories.

PMID- 30291861
TI  - A quantitative analysis of the performance of computing architectures used in
      neural simulations.
AB  - BACKGROUND: Numerical solutions of neuron models are helping neuroscientists gain
      new insights into the behavior of neural systems. Although computing power is
      increasing, the complexity of the systems being simulated is also increasing. If
      the computation is not well matched to the computing hardware, simulations can
      take lengthy times to run, which can make it more difficult to draw inferences
      from those simulations and also to use them in feedback with living neurons such
      as in the dynamic clamp. NEW METHOD: In this paper, we perform a quantitative
      analysis to get a better sense of how much impact the hardware architectures can
      have on simulation performance. Three different architectures are implemented on
      the same hardware platform and compared with respect to simulation time, error,
      and resources used. RESULTS: The results indicate that a lookup table approach to
      evaluate functions can decrease simulation time by orders of magnitude with
      respect to the traditional approach of mathematical operations. COMPARISON WITH
      EXISTING METHOD(S): There are many different ways to implement a lookup table
      approach to evaluate a function. The method presented in this paper sacrifices
      some speed for greater generality and accuracy with respect to other published
      methods. CONCLUSIONS: Lookup tables with 32 interpolation points can dramatically
      speed up computation time of neural simulations without adding significant error.
      In this paper linear interpolation was used, but higher order interpolation could
      be used to further reduce simulation time.

PMID- 30291862
TI  - Regulation of obesity-associated metabolic disturbance by the antipsychotic drug
      olanzapine: Role of the autophagy-lysosome pathway.
AB  - Metabolic disturbance is commonly observed in schizophrenia patients, and the
      metabolic impacts of atypical antipsychotics such as olanzapine (OLA) have
      received much attention. Drug naive schizophrenia patients display metabolic
      abnormality to varying degrees, but how this shapes the metabolic responses to
      chronic OLA exposure is unknown. Using high-fat diet (HFD, 8 weeks) induced
      obesity, here we explored the metabolic outcome of chronic OLA exposure in
      conditions of pre-existing metabolic disturbance. OLA treatment (2 mg/kg) for 4
      weeks led to markedly reduced body weight and adiposity in obese mice,
      concomitant with reduced adipose inflammation and hepatic steatosis. No
      significant change was observed on insulin sensitivity or energy expenditure
      after OLA exposure. Mechanistically, OLA restored autophagic clearance in the
      subcutaneous adipose tissue of obese mice, in line with its potentiation of
      lysosomal function in adipocytes. The metabolic phenotypes induced by OLA were
      partially reversed by chemical suppression of autolysosome. Together, these data
      uncover distinct metabolic effects of OLA in obesity involving the regulation of
      adipose tissue autophagy, and suggest a complicated link between OLA therapy and
      metabolic disturbance in schizophrenia.

PMID- 30291863
TI  - Tissue-specific gene regulation corresponds with seasonal plasticity in female
      testosterone.
AB  - Testosterone (T) is a sex steroid hormone that often varies seasonally and
      mediates trade-offs between territorial aggression and parental care. Prior work
      has provided key insights into the 'top-down' hypothalamic control of this
      seasonal plasticity in T, yet mechanisms acting outside of the brain may also
      influence circulating T levels. We hypothesized that peripheral mechanisms may be
      especially critical for females, because peripheral regulation may mitigate the
      costs of systemically elevated T. Here, we begin to test this hypothesis using a
      seasonal comparative approach, measuring gene expression in peripheral tissues in
      tree swallows (Tachycineta bicolor), a songbird with intense female-female
      competition and T-mediated aggression. We focused on the gonad and liver for
      their role in T production and metabolism, respectively, and we contrasted
      females captured during territory establishment versus incubation. During
      territory establishment, when T levels are highest, we found elevated gene
      expression of the hepatic steroid metabolizing enzyme CYP2C19 along with several
      ovarian steroidogenic enzymes, including the androgenic 5alpha-reductase. Despite
      these seasonal changes in gene expression along the steroidogenic pathway, we did
      not observe seasonal changes in sensitivity to upstream signals, measured as
      ovarian mRNA abundance of luteinizing hormone receptor. Together, these data
      suggest that differential regulation of steroidogenic gene expression in the
      ovary is a potentially major contributor to seasonal changes in T levels in
      females. Furthermore, these data provide a unique and organismal glimpse into
      tissue-specific gene regulation and its potential role in hormonal plasticity in
      females.

PMID- 30291864
TI  - Using a keratinase to degrade chicken feathers for improved extraction of
      glucocorticoids.
AB  - Stress in animals is a concern in conservation breeding programs and livestock
      production facilities. The biological stress response is mediated by the release
      of glucocorticoids, which can suppress reproduction, growth, and immunity if
      recurrently activated. Feathers can be used to extract and monitor concentrations
      of corticosterone, a primary glucocorticoid in birds. However, current techniques
      for extracting feather corticosterone present challenges, including difficulty
      assessing extraction efficiency or hormone recovery, inconsistent extraction
      across feather lengths or pieces, and several uncertainties regarding the
      mechanisms of hormone deposition into feathers. To overcome such challenges and
      to provide tools useful for facilitating conservation breeding and livestock
      production, we developed and validated an alternative procedure for extracting
      feather glucocorticoids. We first developed a protocol to enzymatically digest
      the protein matrix of feathers using a keratinase, such that non-protein analytes
      could be isolated by organic extraction. We then developed an extraction protocol
      and evaluated techniques by measuring extraction efficiency and by testing
      parallelism and hormone recovery (accuracy) using radioimmunoassay. Our results
      demonstrated high and consistent extraction efficiency, as well as high accuracy
      and reliable parallelism to a standard curve upon measurement of corticosterone
      concentrations from extracts. By dissolving feather material into solution prior
      to extraction, we were able to replicate hormone deposition into the feather
      matrix and ensure consistent extraction across feathers. This work provides
      additional support for the validity and practicality of extracting
      glucocorticoids from feathers. Our extraction protocol is likely to extend to
      other applications as well, including the isolation of numerous non-protein
      analytes from various keratinized tissues.

PMID- 30291865
TI  - Performance of Bt-susceptible and -heterozygous genotypes of Spodoptera
      frugiperda (J.E. Smith) possessing single- or dual-gene resistance alleles in
      sequential feedings of non-Bt and Cry1A.105/Cry2Ab2 maize leaf tissues.
AB  - We simulated larval feeding behavior in seed blends of non-Bt and Bt maize to
      determine if seed blends create more favorable conditions for heterozygous
      resistant insects over their Bt-susceptible counterparts. Survival, growth,
      development, and progeny production of four genotypes of the fall armyworm,
      Spodoptera frugiperda, Bt-susceptible (aabb), Cry1A.105 heterozygous resistant
      (Aabb), Cry2Ab2 heterozygous resistant (aaBb), and Cry1A.105/Cry2Ab2 heterozygous
      resistant (AaBb), were evaluated in eight feeding sequences (Seq 1-8) of non-Bt
      and MON89034 Bt maize leaf tissue expressing the Cry1A.105 and Cry2Ab2 proteins.
      We report variation in the performance of the four genotypes across the feeding
      sequences and biological parameters measured. Three heterozygous genotypes
      generally outperformed the susceptible genotype in larval survival, pupation
      rate, pupal weight, and progeny production. The performance was greater for Aabb
      over aaBb, AaBb over Aabb or aaBb, in two of the feeding sequences. The findings
      of this study could have important implications in assessing the risk of seed
      blends as refuge plantings for Bt crop resistance management where resistance in
      the target pest is not functionally recessive.

PMID- 30291866
TI  - Perkinsus olseni in the short neck yellow clam, Paphia malabarica (Chemnitz,
      1782) from the southwest coast of India.
AB  - Parasites of the genus Perkinsus predominantly infect bivalves, and two species
      among them, P. olseni and P. marinus, are notifiable to OIE. P. olseni infections
      are known to cause extensive damage to wild as well as farmed bivalves globally
      with enormous implications to its fishery. Consequent to the initiation of a
      surveillance programme for aquatic animal diseases in India, Perkinsus infections
      were observed in many species of bivalves. The present paper describes P. olseni
      infections in the short neck yellow clam, Paphia malabarica from the southwest
      coast of India. Diagnosis of the parasite was carried out using Ray's Fluid
      Thioglycollate Medium culture, histology, in-situ hybridisation and molecular
      taxonomy. Pathology of infection and development of zoospores is also described.
      This forms the first report of a P. olseni infection in P. malabarica. High
      prevalence and intensity of infection of Perkinsus in clams raises concerns, as
      clam reserves in this geographical area sustain fisheries and the livelihoods of
      local fishing communities.

PMID- 30291867
TI  - NEAT1 contributes to the CSC-like traits of A549/CDDP cells via activating Wnt
      signaling pathway.
AB  - Long non-coding RNAs (lncRNAs) have been identified to exert crucial roles in
      tumorigenesis and can serve as novel biomarkers for cancer therapy including lung
      cancer. Cisplatin is a first-line chemotherapeutic agent in non-small cell lung
      cancer (NSCLC), but the therapeutic effect is unsatisfactory, partly due to drug
      resistance. Emerging evidence showed that chemo-resistance is associated with
      acquisition of cancer stem cell (CSC)-like properties. Cisplatin resistance
      remains a major obstacle in the treatment of lung cancer, and its mechanism is
      still not fully elucidated. Meanwhile, CSCs have been involved in tumor
      metastasis, tumor recurrence and chemotherapy resistance. So far, the mechanism
      of nuclear enriched abundant transcript 1 (NEAT1) in modulating CSCs in lung
      cancer remains barely known. Therefore, we aimed to explore the correlation
      between NEAT1 and cancer stem cells in lung cancer. In our current study, we
      observed that CSC-like traits were much more enriched in cisplatin-resistant
      A549/CDDP cells. In addition, NEAT1 was obviously up-regulated in A549/CDDP cells
      compared with parental A549 cells. Knockdown of NEAT1 decreased the CSC-like
      properties of A549/CDDP cells through inhibiting tumor cell sphere volume,
      repressing CSC-like biomarkers levels and restraining CD44 positive cell ratios.
      Oppositely, overexpression of NEAT1 enhanced the stemness respectively. Moreover,
      it has been reported that Wnt pathway is implicated in many vital cellular
      functions including cancer stem cells. Here, it was exhibited that Wnt signal
      pathway was inactivated by knockdown of NEAT1 whereas activated by NEAT1
      overexpression in A549/CDDP cells. Taken these together, it was indicated that
      NEAT1 could exert a novel biological role in NSCLC chemo-resistance.

PMID- 30291868
TI  - Longitudinal correlations between MRE, MRI-PDFF, and liver histology in patients
      with non-alcoholic steatohepatitis: Analysis of data from a phase II trial of
      selonsertib.
AB  - BACKGROUND & AIMS: Non-invasive tools for monitoring treatment response and
      disease progression in non-alcoholic steatohepatitis (NASH) are needed. Our
      objective was to evaluate the utility of magnetic resonance (MR)-based hepatic
      imaging measures for the assessment of liver histology in patients with NASH.
      METHODS: We analyzed data from patients with NASH and stage 2 or 3 fibrosis
      enrolled in a phase II study of selonsertib. Pre- and post-treatment assessments
      included centrally read MR elastography (MRE)-estimated liver stiffness, MR
      imaging-estimated proton density fat fraction (MRI-PDFF), and liver biopsies
      evaluated according to the NASH Clinical Research Network classification and the
      non-alcoholic fatty liver disease activity score (NAS). RESULTS: Among 54
      patients with MRE and biopsies at baseline and week 24, 18 (33%) had fibrosis
      improvement (>=1-stage reduction) after undergoing 24 weeks of treatment with the
      study drug. The area under the receiver operating characteristic curve (AUROC) of
      MRE-stiffness to predict fibrosis improvement was 0.62 (95% CI 0.46-0.78) and the
      optimal threshold was a >=0% relative reduction. At this threshold, MRE had 67%
      sensitivity, 64% specificity, 48% positive predictive value, 79% negative
      predictive value. Among 65 patients with MRI-PDFF and biopsies at baseline and
      week 24, a >=1-grade reduction in steatosis was observed in 18 (28%). The AUROC
      of MRI-PDFF to predict steatosis response was 0.70 (95% CI 0.57-0.83) and the
      optimal threshold was a >=0% relative reduction. At this threshold, MRI-PDFF had
      89% sensitivity and 47% specificity, 39% positive predictive value, and 92%
      negative predictive value. CONCLUSIONS: These preliminary data support the
      further evaluation of MRE-stiffness and MRI-PDFF for the longitudinal assessment
      of histologic response in patients with NASH. LAY SUMMARY: Liver biopsy is a
      potentially painful and risky method to assess damage to the liver due to non
      alcoholic steatohepatitis (NASH). We analyzed data from a clinical trial to
      determine if 2 methods of magnetic resonance imaging - 1 to measure liver fat and
      1 to measure liver fibrosis (scarring) - could potentially replace liver biopsy
      in evaluating NASH-related liver injury. Both imaging methods were correlated
      with biopsy in showing the effects of NASH on the liver.

PMID- 30291869
TI  - Amphiregulin potentiates airway inflammation and mucus hypersecretion induced by
      urban particulate matter via the EGFR-PI3Kalpha-AKT/ERK pathway.
AB  - Ambient particulate matter (PM) promotes the development and exacerbation of
      chronic respiratory diseases, including chronic obstructive pulmonary disease
      (COPD) and asthma, by increasing inflammation and mucus hypersecretion. However,
      the biological mechanisms underlying PM-induced airway inflammation and mucus
      hypersecretion remain unclear. Amphiregulin (AREG) is an important ligand for
      epidermal growth factor receptor (EGFR) and participates in the regulation of
      several biological functions. Here, the PM-exposed human bronchial epithelial
      cell (HBEC) model was used to define the role of AREG in PM-induced inflammation
      and mucus hypersecretion and its related signaling pathways. The expression of
      AREG was significantly increased in a dose-dependent manner in HBECs subjected to
      PM exposure. Moreover, PM could induce inflammation and mucus hypersecretion by
      upregulating the expression of IL-1alpha, IL-1beta, and Muc-5ac in HBECs. The
      EGFR, AKT, and ERK signaling pathways were also activated in a time- and dose
      dependent manner. The AREG siRNA markedly attenuated PM-induced inflammation and
      mucus hypersecretion, and activation of the EGFR-AKT/ERK pathway. Exogenous AREG
      significantly increased the expression of IL-1alpha, IL-1beta, and Muc-5ac, and
      induced activation of the EGFR-AKT/ERK pathway in HBECs. Further, under PM
      exposure, exogenous AREG significantly potentiated PM-induced inflammation and
      mucus hypersecretion, and activation of the EGFR-AKT/ERK pathway. Tumor-necrosis
      factor-alpha converting enzyme (TACE) and EGFR specific inhibitor pretreatment
      showed that AREG was secreted by TACE-mediated cleavage to regulate PM-induced
      inflammation and mucus hypersecretion by binding to the EGFR. Moreover, according
      to the inhibitory effect of specific inhibitors of the class I PI3K isoforms, AKT
      and ERK, PM-induced inflammation and mucus hypersecretion was regulated by
      PI3Kalpha activation and its downstream AKT and ERK pathways. This study strongly
      suggests the adverse effect of AREG in PM-induced inflammation and mucus
      hypersecretion via the EGFR-PI3Kalpha-AKT/ERK pathway. These findings contribute
      to a better understanding of the biological mechanisms underlying exacerbation of
      chronic respiratory diseases induced by PM exposure.

PMID- 30291870
TI  - Prevalence of latent tuberculosis infection in transplant candidates: A
      systematic review and meta-analysis.
AB  - INTRODUCTION: Tuberculosis (TB) is considered as a serious complication for organ
      transplant recipients; therefore, the detection and appropriate treatment of
      latent infection are recommended for preventing active TB infections in the
      future. The objective of this review is to conduct a systematic review and meta
      analysis of studies assessing the prevalence of latent TB infection (LTBI) in
      transplant candidates. METHODS: Electronic databases, including MEDLINE (via
      PubMed), SCOPUS were searched until 30 June 2017. The prevalence of LTBI was
      estimated using the random effects meta-analysis. Heterogeneity was evaluated by
      subgroup analysis. Data were analyzed by STATA version 14. RESULTS: The pooled
      prevalence of LTBI based on tuberculin skin test (TST) in different transplant
      types was as follows: liver 24% (14%-33%, 95% CI), lung 22% (18%-26%), renal 21%
      (16%-27%, 95% CI) and hematopoietic stem cell transplantation (HCT) 14% (9%-19%).
      The prevalence of LTBI based on Interferon Gamma Release Assay (IGRA) tests in
      renal transplant candidates was 31% (95% CI; 25-37%), which was much higher than
      the prevalence of LTBI in liver transplant candidates (25%, 95% CI; 17-33%) and
      HCT transplant candidates (13%, 95% CI; 10-16%) and there was statistically
      significant differences between them. The pooled prevalence of indeterminate
      results based on IGRAs test in different transplant types was as follows: renal
      6% (4%-8%, 95% CI) and liver 12% (2%-21%, 95% CI). Subgroup analysis revealed
      that there were statistically significant differences between the overall
      prevalence of indeterminate results by using IGRA tests in liver transplant
      candidates (12%, 95% CI; 2-21%) and renal transplant candidates (6%, 95% CI; 4
      8%). The pooled prevalence of post-transplant TB was 2% (1%-2%, 95% CI) and its
      occurrence was more common in renal recipients (4% (2%-7%, 95% CI)) than in the
      liver transplant patients (1% (0%-2%, 95% CI)). The prevalence of LTBI in the
      subgroup (i.e. the patients' mean age was <50 years) was significantly higher
      than the prevalence of LTBI by using TST/IGRAs in the other subgroup (i.e. the
      patients' mean age was >=50 years). CONCLUSION: Our study suggests fair overall
      agreement between IGRAs and TST in patients requiring liver and HCT
      transplantation, while a superiority of IGRAs over TST in patients requiring
      renal transplantation was seen.

PMID- 30291871
TI  - Mutations in the HFE gene can be associated with increased lung disease severity
      in cystic fibrosis.
AB  - BACKGROUND AND OBJECTIVE: Genetic modifiers contribute to variable disease
      phenotype in cystic fibrosis (CF). We explored the association between mutations
      in the hemochromatosis (HFE) gene and disease severity in adults with CF.
      METHODS: HFE genotyping was performed in 163 adults with CF attending a single
      centre. Results were correlated with lung disease severity, prevalence of CF
      related diabetes (CFRD) and history of meconium ileus (MI) or distal intestinal
      obstruction syndrome (DIOS). RESULTS: Subjects with the C282Y substitution in the
      HFE protein (C282Y mutation) had a lower FEV1 percentage predicted (54% versus
      66%, p = 0.029) and accelerated rate of FEV1 decline (-110 mL versus -80 mL per
      year respectively, p < 0.001) compared to subjects with a normal HFE genotype.
      C282Y substitutions were associated with increased rates of CFRD (58% versus 33%,
      p = 0.026) and a trend towards increased MI or DIOS (38% versus 19%, p = 0.05).
      H63D HFE substitutions were associated with a more rapid rate of decline in
      forced vital capacity (p = 0.01) and increased risk of MI or DIOS (p = 0.02).
      CONCLUSIONS: In subjects with CF, the C282Y HFE substitution was associated with
      worse lung function, and increased rates of CFRD and gastrointestinal
      complications. The H63D HFE substitution also impacted on disease phenotype, but
      to a lesser extent. The results support a role for HFE gene mutations as
      modifiers of CF phenotype.

PMID- 30291872
TI  - Identification of several key genes by microarray data analysis of bovine mammary
      gland epithelial cells challenged with Escherichia coli and Staphylococcus
      aureus.
AB  - PURPOSE: This study was aimed at exploring the mechanisms and identifying the key
      candidate genes associated with S. aureus and E. coli mastitis. METHODS: A public
      microarray dataset GSE24560 was downloaded. Differentially expressed genes (DEGs)
      were screened in E. coli- and S. aureus-infected primary bovine mammary gland
      epithelial cell (pBMEC) samples, and compared with control samples at 1 h, 6 h,
      and 24 h. A functional enrichment analysis was performed, and construction of a
      gene co-expression network was performed based on genes that showed consistent
      changes over time, which were identified using time series expression analysis.
      Then, a miRNA/TF regulatory network was constructed based on the genes in the co
      expression network. The genes in the miRNA/TF regulatory network were screened
      for involvement in related diseases. Furthermore, the expression of several
      selected DEGs was further validated using real-time RT-PCR. RESULTS: In total, 92
      and 81 DEGs showed continuous differential expression over time in the E. coli-
      and S. aureus-inoculated groups. DEGs in the E. coli-inoculated group were
      associated with the RIG-I-like receptor signaling pathway, and those in the S.
      aureus-inoculated group were associated with the lysosome pathway. Time series
      expression analysis identified two gene clusters. NFKBIZ and GRO1 in the gene co
      expression network were associated with inflammatory and defense responses.
      Moreover, several genes such as CXADR, APP, and CXCL2 in the miRNA/TF regulatory
      network, were associated with infection, inflammation, or stress-related
      diseases. CONCLUSION: RIG-I like receptor pathway and several DEGs such as
      NFKBIZ, GRO1, CXCL2, and CXADR may play critical roles in the response to
      infection in pBMECs.

PMID- 30291873
TI  - Neuronal and astrocytic primary cilia in the mature brain.
AB  - Primary cilia are tiny microtubule-based signaling devices that regulate a
      variety of physiological functions, including metabolism and cell division.
      Defects in primary cilia lead to a myriad of diseases in humans such as obesity
      and cancers. In the mature brain, both neurons and astrocytes contain a single
      primary cilium. Although neuronal primary cilia are not directly involved in
      synaptic communication, their pathophysiological impacts on obesity and mental
      disorders are well recognized. In contrast, research on astrocytic primary cilia
      lags far behind. Currently, little is known about their functions and molecular
      pathways in the mature brain. Unlike neurons, postnatal astrocytes retain the
      capacity of cell division and can become reactive and proliferate in response to
      various brain insults such as epilepsy, ischemia, traumatic brain injury, and
      neurodegenerative beta-amyloid plaques. Since primary cilia derive from the
      mother centrioles, astrocyte proliferation must occur in coordination with the
      dismantling and ciliogenesis of astrocyte cilia. In this regard, the functions,
      signal pathways, and structural dynamics of neuronal and astrocytic primary cilia
      are fundamentally different. Here we discuss and compare the current
      understanding of neuronal and astrocytic primary cilia.

PMID- 30291874
TI  - LVQ-KNN: Composition-based DNA/RNA binning of short nucleotide sequences
      utilizing a prototype-based k-nearest neighbor approach.
AB  - Unbiased sequencing is an upcoming method to gain information of the microbiome
      in a sample and for the detection of unrecognized pathogens. There are many
      software tools for a taxonomic classification of such metagenomics datasets
      available. Numerous of them have a satisfactory sensitivity and specificity for
      known organisms, but they fail if the sample contains unknown organisms, which
      cannot be detected by similarity-based classification employing available
      databases. However, recognition of unknowns is especially important for the
      detection of newly emerging pathogens, which are often RNA viruses. Here we
      present the composition-based analysis tool LVQ-KNN for binning unclassified
      nucleotide sequence reads into their provenance classes DNA or RNA. With a 5-fold
      cross-validation, LVQ-KNN reached correct classification rates (CCR) of up to
      99.9% for the classification into DNA/RNA. Real datasets gained CCRs of up to
      94.5%. Comparing the method to another composition-based analysis tool, similar
      or better classification results were reached. LVQ-KNN is a new tool for DNA/RNA
      classification of sequence reads from unbiased sequencing approaches that could
      be applicable for the detection of yet unknown RNA viruses in metagenomic
      samples. The source-code, training and test data for LVQ-KNN is available at
      Github (https://github.com/ab1989/LVQ-KNN).

PMID- 30291875
TI  - One-step multiplex real-time RT-PCR for detection and typing of dengue virus.
AB  - Previous studies reported that severity of dengue is associated with multiple
      factors, including secondary infection, age, viral load and infecting serotype
      and genotype. In addition, other studies have reported that a dengue virus-2
      (DENV-2) infection is associated with a prognosis of more severe clinical
      manifestations than DENV-1 and DENV-4 infections. For these reasons, the ability
      to identify the DENV serotypes is critical for optimal patient diagnosis and
      epidemiological studies. In this study, we developed a TaqMan probe-based, one
      step real-time reverse transcriptase-polymerase chain reaction (RT-PCR) system
      for detection and serotyping DENV. Our linear dynamic range (101 to 107
      copies/reaction) showed the R2 values of DENV-1, 2, 3 and 4 as 0.998, 0.998,
      0.994, and 0.998, respectively. The detection limits of DENV-1, 2, 3, and 4, were
      10 copies/reaction, 100 copies/reaction, 10 copies/reaction, and 100
      copies/reaction, respectively. Specificity test results indicated that this
      system is specific for DENV-1, 2, 3, and 4 and does not react with other viruses.
      Finally, we validated our results with five different real-time PCR instruments.
      Our results showed that the Ct values of the four serotype templates were similar
      in five real-time PCR instruments. Thus, this system provides an accurate method
      for detection and serotyping of DENV, which can be applied in diagnostics,
      surveillance, and epidemiology. Dengue can be found in many nations with varying
      socioeconomic and monetary resources. The results of our validation analyses
      using five different real-time PCR instruments suggest that this method can
      easily and confidently be used world-wide.

PMID- 30291876
TI  - Temporal dynamics of audiovisual affective processing.
AB  - This study used event-related potentials (ERPs) to investigate the time course of
      auditory, visual, and audiovisual affective processing. Stimuli consisted of
      naturalistic silent videos, instrumental music clips, or combination of the two,
      with valence varied at three levels for each modality and arousal matched across
      valence conditions. Affective ratings of the unimodal and multimodal stimuli
      showed evidence of visual dominance, congruency, and negativity dominance
      effects. ERP results for unimodal presentations revealed valence effects in early
      components for both modalities, but only for the visual condition in a late
      positive potential. The ERP results for multimodal presentations showed effects
      for both visual valence and auditory valence in three components, early N200,
      P300 and LPP. A modeling analysis of the N200 component suggested its role in the
      visual dominance effect, which was further supported by a correlation between
      behavioral visual dominance scores and the early ERP components. Significant
      congruency comparisons were also found for N200 amplitudes, suggesting that
      congruency effects may occur early. Consistent differences between negative and
      positive valence were found for both visual and auditory modalities in the P300
      at anterior electrode clusters, suggesting a potential source for the negativity
      dominance effect observed behaviorally. The separation between negative and
      positive valence also occurred at LPP for the visual modality. Significant
      auditory valence modulation was found for the LPP, implying an integration effect
      in which valence sensitivity of the LPP emerged for the audiovisual condition.
      These results provide a basis for mapping out the temporal dynamics of
      audiovisual affective processing.

PMID- 30291877
TI  - Bioavailability of protein therapeutics in rats following inhalation exposure:
      Relevance to occupational exposure limit calculations.
AB  - Protein therapeutics represent a rapidly growing proportion of new medicines
      being developed by the pharmaceutical industry. As with any new drug, an
      Occupational Exposure Limit (OEL) should be developed to ensure worker safety.
      Part of the OEL determination addresses bioavailability (BA) after inhalation,
      which is poorly understood for protein therapeutics. To explore this, male
      Sprague-Dawley rats were exposed intravenously or by nose-only inhalation to one
      of five test proteins of varying molecular size (10-150 kDa), including a
      polyethylene glycol-conjugated protein. Blood, lung tissue and bronchoalveolar
      lavage (BAL) fluid were collected over various time-points depending on the
      expected test protein clearance (8 minutes-56 days), and analyzed to determine
      the pharmacokinetic profiles. Since the BAL half-life of the test proteins was
      observed to be > 4.5 h after an inhalation exposure, accumulation and direct lung
      effects should be considered in the hazard assessment for protein therapeutics
      with lung-specific targets. The key finding was the low systemic bioavailability
      after inhalation exposure for all test proteins (~<=1%) which did not appear
      molecular weight-dependent. Given that this study examined the inhalation of
      typical protein therapeutics in a manner mimicking worker exposure, a default 1%
      BA assumption is reasonable to utilize when calculating OELs for protein
      therapeutics.

PMID- 30291878
TI  - The regulatory challenge of chemicals in the environment: Toxicity testing, risk
      assessment, and decision-making models.
AB  - Environmental assessment for chemicals relies on models of fate, exposure,
      toxicity, risk, and impacts. Together, these models should provide scientific
      support for regulatory risk management decision-making, assuming that progress
      through the data-information-knowledge-wisdom (DIKW) hierarchy is both
      appropriate and sufficient. Improving existing regulatory processes necessitates
      continuing enhancement of interpretation and evaluation of key data for use in
      decision-making schemes, including ecotoxicity testing data, physical-chemical
      properties, and environmental fate processes. Yet, as environmental objectives
      also increase in scope and sophistication to encompass a safe chemical economy,
      testing, risk assessment, and decision-making are subject to additional
      complexity due to the ongoing interaction between science and policy models.
      Problems associated with existing design and implementation choices in science
      and policy have both limited needed development beyond chemo-centric
      environmental risk assessment modeling and constrained needed improvements in
      environmental decision-making. Without a thorough understanding of either the
      scientific foundations or the disparate evaluation processes for validation,
      quality, and relevance, this results in complex technical and philosophical
      problems that increase costs and decrease productivity. Both over- and under
      management of chemicals are consequences of failure to validate key model
      assumptions, unjustified standardized views on data selection, and inordinate
      reification (i.e., abstract concepts are wrongly treated as facts).

PMID- 30291879
TI  - The expression of adenosine receptors changes throughout light induced retinal
      degeneration in the rat.
AB  - The modulation of adenosine receptors, A1 (A1R) and A2A (A2AR), is
      neuroprotective in different models of retinal injury. In order to understand the
      processes underlying retinal degeneration, we studied the expression of adenosine
      receptors in the retinas of control and continuously illuminated (CI) rats by qRT
      PCR, Western blot (WB) and immunohistochemistry (IHC). Significant increases of
      A1R, A2AR, and A2BR mRNAs at 1, 5, and 7 days of CI (P < 0.0001) were observed by
      qRT-PCR. Also, a significant increase of A3R mRNA was detected after 5 and 7 days
      of CI. WB studies showed a significant rise of A1R on day 1 of CI and on days 5
      and 7 (P < 0.0001), while A2AR increase was seen from 2 days of CI on (P <
      0.001). After 1 day of CI, A1R immunoreactivity (A1R-IR) increased in ganglion
      cell layer, inner nuclear layer, and in both the outer and inner plexiform
      layers. After 2 days of CI, the A1R-IR went back to control levels. After 5 days
      of CI, a second rise in A1R, which persisted until 7 days of CI, was measured (P
      < 0.0001). A significant rise of A2aR immunoreactivity was also observed at day 2
      of CI at GCL and INL and subsided at days 5 and 7 (P < 0.0001). The observed up
      regulation of A1R after 1 day of CI, corresponds with the peak of oxidative
      stress; while the rise of A2aR at day 2 of CI, coincides with the massive
      apoptosis of photoreceptors. We postulate that an early modulation of adenosine
      receptors could delay or prevent the degeneration of photoreceptors.

PMID- 30291881
TI  - Antibacterial activity of lysozyme-binding proteins from chicken egg white.
AB  - The purpose of this study was to establish a method for determining the
      bacteriolytic activity after separation of lysozyme-binding proteins from egg
      white. Lysozyme-binding proteins such as ovotransferrin and ovalbumin were
      separated by non-denaturing two-dimensional electrophoresis (2DE) and transferred
      to a membrane. The lysozyme activity of the separated and immobilized egg white
      proteins was assessed directly to produce a non-denaturing 3D map of the egg
      white proteins by incorporating an axis that combined each spot's lysozyme
      activity with the non-denaturing 2DE pattern. Lysozyme-ovotransferrin and
      lysozyme-ovalbumin complexes could be reconstructed in vitro after the cathode
      end fraction containing lysozyme was added to purified ovotransferrin and
      ovalbumin, respectively. These complexes retained lysozyme activity even after
      separation by non-denaturing 2DE. Furthermore, when the lysozyme-ovotransferrin
      complex from egg white was extracted after separation by isoelectric focusing by
      replacing the cathodic sodium hydroxide solution with phosphoric acid solution,
      the complex possessed bacteriolytic activity against both Bacillus subtilis and
      Escherichia coli. These methods can be applied to investigate protein complexes
      possessing bacteriolytic activity against a wide range of both Gram-positive and
      Gram-negative bacteria.

PMID- 30291880
TI  - MicroRNA-21 attenuates oxygen and glucose deprivation induced apoptotic death in
      human neural stem cells with inhibition of JNK and p38 MAPK signaling.
AB  - Neural stem cells (NSCs) persist in the mammalian brain throughout life and
      protect against hypoxia-ischemia injury. NSCs are being increasingly recognized
      as a novel therapeutic target for various neurological disorders. Previous
      research indicates that miR-21 attenuates hypoxia-ischemia induced apoptotic
      death in various cell types. However, whether miR-21 plays a role in this
      protective effect mediated by NSCs is unknown, particularly in human NSCs
      (hNSCs). The present study investigated whether miR-21 could prevent hNSC injury
      induced by oxygen and glucose deprivation (OGD). Upon challenge with OGD
      treatment, loss of cell viability was observed in cultured hNSCs, as shown by CCK
      8 assay. Moreover, quantitative real-time PCR (qRT-PCR) analysis indicated that
      expression of miR-21 increased in a time-dependent manner. TUNEL staining and
      Western blotting analysis showed that overexpression of miR-21 inhibited
      excessive hNSCs death induced by OGD treatment. Accordingly, knock down of miR-21
      attenuated the neuroprotective effect observed in response to OGD treatment.
      Furthermore, JNK and p38 MAPKs inhibition was observed after overexpression of
      miR-21, and knock down of miR-21 had the opposite effect. We suggest that miR-21
      prevents OGD-induced hNSCs death and apoptotic-associated protein activities
      through inhibiting JNK and p38 pathways in cultured hNSCs. Our findings may help
      to develop strategies for enhancing resident and transplanted NSCs survival after
      hypoxia-ischemic brain damage.

PMID- 30291882
TI  - Identification of Escherichia coli strains for the heterologous overexpression of
      soluble Clostridium difficile exosporium proteins.
AB  - Clostridium difficile infections are one of the leading causes of hospital
      acquired infections. C. difficile spores are considered the morphotype of
      transmission and recurrent infection due to its natural spore resistance
      properties. The outermost spore layer, the exosporium, provides the first contact
      with the environment and the host. However, molecular biology studies on
      exosporium proteins are lacking primarily due to difficulties in over-expressing
      these proteins under soluble conditions. In this work, we have developed a
      protocol to express soluble exosporium proteins of C. difficile spores in the
      heterologous Escherichia coli host. We found that the optimum soluble expression
      conditions may vary between 21, 30 and 37  degrees C, depending on the protein,
      and at least CdeC, BclA1 and BclA3, required E. coli strains that provided an
      oxidative environment such as Shuffle T7. These results will allow further
      studies with recombinant proteins of the exosporium of C. difficile spores.

PMID- 30291883
TI  - Therapeutic hypothermia after paediatric cardiac arrest: Pooled randomized
      controlled trials.
AB  - BACKGROUND: Separate trials to evaluate therapeutic hypothermia after paediatric
      cardiac arrest for out-of-hospital and in-hospital settings reported no
      statistically significant differences in survival with favourable neurobehavioral
      outcome or safety compared to therapeutic normothermia. However, larger sample
      sizes might detect smaller clinical effects. Our aim was to pool data from
      identically conducted trials to approximately double the sample size of the
      individual trials yielding greater statistical power to compare outcomes.
      METHODS: Combine individual patient data from two clinical trials set in forty
      one paediatric intensive care units in USA, Canada and UK. Children aged at least
      48 h up to 18 years old, who remained comatose after resuscitation, were
      randomized within 6 h of return of circulation to hypothermia or normothermia
      (target 33.0  degrees C or 36.8  degrees C). The primary outcome, survival 12
      months post-arrest with Vineland Adaptive Behaviour Scales, Second Edition (VABS
      II) score at least 70 (scored from 20 to 160, higher scores reflecting better
      function, population mean = 100, SD = 15), was evaluated among patients with pre
      arrest scores >=70. RESULTS: 624 patients were randomized. Among 517 with pre
      arrest VABS-II scores >=70, the primary outcome did not significantly differ
      between hypothermia and normothermia groups (28% [75/271] and 26% [63/246],
      respectively; relative risk, 1.08; 95% confidence interval [CI], 0.81 to 1.42; p
      = 0.61). Among 602 evaluable patients, the change in VABS-II score from baseline
      to 12 months did not differ significantly between groups (p = 0.20), nor did,
      proportion of cases with declines no more than 15 points or improvement from
      baseline [22% (hypothermia) and 21% (normothermia)]. One-year survival did not
      differ significantly between hypothermia and normothermia groups (44% [138/317]
      and 38% [113/ 297], respectively; relative risk, 1.15; 95% CI, 0.95 to 1.38; p =
      0.15). Incidences of blood-product use, infection, and serious cardiac arrhythmia
      adverse events, and 28-day mortality, did not differ between groups. CONCLUSIONS:
      Analysis of combined data from two paediatric cardiac arrest targeted temperature
      management trials including both in-hospital and out-of-hospital cases revealed
      that hypothermia, as compared with normothermia, did not confer a significant
      benefit in survival with favourable functional outcome at one year.

PMID- 30291884
TI  - Number of treating team reviews prior to rapid response team activation.

PMID- 30291885
TI  - Evolution as a search for organizational equilibrium.
AB  - Evolution of living systems is a succession of historical changes in their
      equilibrium states. In the individual life cycle, every such state is realized as
      an equilibrium of developmental system, i.e. as its adult organizational norm. A
      trigger for a switching the system to a search for a new equilibrium is the loss
      under critical conditions of effective regulation of normal development towards
      uniform final state. This is manifested by replacement of the adult norm by its
      individual deviations. Thus, the organizational change begins with its adult
      state, which is the first to undergo the disturbance under new conditions.
      Accordingly, with the transition of the organization to a new equilibrium, the
      remodeling of the developmental system extends in generations from the adult
      stage to earlier ones. These premises contrast with the accepted belief that
      evolutionary events begin with individual changes in the germ cell. The only
      substantiated alternative to the last approach is objectively presented by the
      concepts of Schmalhausen and Waddington, in which the change in systemic
      organization starts with stabilization of selected phenotypic variations
      generated by violation of the current adult norm. The evolutionary spreading of
      organizational changes towards the early developmental stages constitutes in this
      case a natural consequence of the stabilization process. This course of events is
      actually reflected in different ways in the many empirical generalizations that
      have grown in the scope of more traditional views. It may be predicted that this
      pattern will come to provide a basis for a revised understanding of the
      evolutionary process.

PMID- 30291887
TI  - Axillary Transcatheter Aortic Valve Replacement in Patients With Peripheral
      Vascular Disease.
AB  - The axillary artery seems an interesting alternative in nonfemoral transaortic
      valve replacement (TAVR) patients. This study describes our experience with this
      technique and its short-term follow-up results. This is a retrospective single
      center study. All axillary TAVR performed in our department between 2015 and 2017
      were included in the study. Mean follow-up was 13.2 +/- 9.5 months. All reporting
      was done according to the VARC-2 criteria. During the period covered, 43 patients
      had an axillary TAVR. Most patients were men (62.7%), had a mean age of 83.9 +/-
      5.3 years and presented with EuroSCORE I, II, and STS score of 27.9 +/- 13.5%,
      5.6 +/- 4.9%, and 7.7 +/- 4.05%, respectively. Vascular access was successful in
      all patients with a higher frequency of left approach (69.7%, n = 30). Both
      Medtronic CoreValve 37.2% (n = 16) and Edwards Sapien3 62.8% (n = 27) valves were
      used. An apical Certitude delivery system was preferentially used (24/27) in the
      latter group. There were no reported instances of valve migration or need for a
      second valve implantation. A single case (2.3%) of arterial vascular complication
      was reported. Central neurologic morbidity was 2.3%. No patient experienced
      brachial plexus injury. A pacemaker was implanted in 18.6% of cases (n = 8), with
      no significant difference between the 2 valves patient groups (S3 14.8% vs CV
      25%, P 0.67). The 30-day mortality was 6.9% (n = 3) and 1-year survival was 86%
      [95% CI 72.6, 93.4]. Axillary TAVR is associated with acceptable morbidity,
      mortality, and leads to satisfactory short-term clinical outcomes. It has the
      potential to become the main alternative access route in nonfemoral TAVR
      patients.

PMID- 30291886
TI  - Biglycan gene connects metabolic dysfunction with brain disorder.
AB  - Dietary fructose is a major contributor to the epidemic of diabetes and obesity,
      and it is an excellent model to study metabolic syndrome. Based on previous
      studies that Bgn gene occupies a central position in a network of genes in the
      brain in response to fructose consumption, we assessed the capacity of Bgn to
      modulate the action of fructose on brain and body. We exposed male biglycan
      knockout mice (Bgn0/-) to fructose for 7 weeks, and results showed that Bgn0/-
      mice compensated for a decrement in learning and memory performance when exposed
      to fructose. These results were consistent with an attenuation of the action of
      fructose on hippocampal CREB levels. Fructose also reduced the levels of CREB and
      BDNF in primary hippocampal neuronal cultures. Bgn siRNA treatment abolished
      these effects of fructose on CREB and BDNF levels, in conjunction with a
      reduction in a fructose-related increase in Bgn protein. In addition, fructose
      consumption perturbed the systemic metabolism of glucose and lipids, that were
      also altered in the Bgn0/ mice. Transcriptomic profiling of hypothalamus,
      hippocampus, and liver supported the regulatory action of Bgn on key molecular
      pathways involved in metabolism, immune response, and neuronal plasticity.
      Overall results underscore the tissue-specific role of the extracellular matrix
      in the regulation of metabolism and brain function, and support Bgn as a key
      modulator for the impact of fructose across body and brain.

PMID- 30291888
TI  - Functional Evaluation of the Myocardial Ischemia after Coronary Artery Bypass
      Surgery using Coronary Flow Velocity Reserve in Left Ventricular Hypertrophy.
AB  - BACKGROUND: Patients with left ventricular hypertrophy (LVH) have reportedly
      higher than normal mortality and incidences of cardiovascular events. Coronary
      microvascular pathophysiology also appears to differ from other populations. Such
      coronary microcirculation dysfunctions are considered strong causes of cardiac
      events. OBJECTIVES: We compare the functional improvement of myocardial ischemia
      between LVH patients and other patients after successful coronary artery bypass
      surgery (CABG) using coronary flow velocity reserve (CFVR) by transthoracic echo
      cardiography. METHODS: Patients who underwent isolated coronary artery bypass
      surgery, including left anterior descending artery (LAD) revascularization via
      'in-situ' internal thoracic artery (ITA) between June 2008 and July 2017 (n:155),
      were retrospectively reviewed. ITA grafts were patent in postoperative graft
      evaluation in all patients. Coronary flow velocity reserve was evaluated pre- and
      post-operatively, and data were compared between patients with severe left
      ventricular hypertrophy (LVH group) and those without (Non-LVH group). RESULTS:
      Preoperative mean CFVR was 1.77 +/- 0.75 in LVH group and 1.91 +/- 0.63 in Non
      LVH group (p=0.188). After the operation, ITA to LAD graft patency was confirmed
      in all patients. Postoperative CFVR was 2.23 +/- 0.70 in LVH group and 2.85 +/-
      0.71 in Non-LVH group, respectively (p=0.002). Significant difference was
      observed between the two groups. CONCLUSION: CFVR values improved after ITA to
      LAD bypass grafting in both LVH and Non-LVH groups, but postoperative CFVR was
      significantly lower in patients with severe left ventricular hypertrophy than in
      patients without. Myocardial ischemia may exist in patients with left ventricular
      hypertrophy, despite patent graft, due to microvascular dysfunction.
      Comprehensive treatment, including long-term oral medication to improve
      microvascular dysfunction, is necessary for patients with left ventricular
      hypertrophy.

PMID- 30291889
TI  - Anaplastic large cell lymphoma of the palate: A case report.
AB  - Anaplastic large cell lymphoma (ALCL) is a very rare subtype of T-cell non
      Hodgkin's lymphoma (NHL). Similar to other types of NHL, ALCL primarily involves
      the nodal areas and sometimes it can involve several extranodal sites such as
      skin, lung and soft tissue. Primary oral involvement of systemic ALCL is very
      rare. We report a 55-year-old Thai female with anaplastic lymphoma kinase (ALK)
      negative ALCL primarily occurring at the hard palate. The patient was referred to
      the Department of Oral and Maxillofacial Surgery, Mahidol University, complaining
      of a swelling on her left palate. An incisional biopsy was performed and revealed
      a diffuse infiltration of large pleomorphic cells with prominent nuclei and
      sometimes eccentric horseshoe-shaped nuclei. The tumor cells showed a positivity
      for CD30, CD2, CD4, CD43 and EMA. A few tumor cells were positive to CD45 and
      CD3. They were negative for CD5, CD8, CD20, AE1/AE3, HMB45, ALK, TCRalphabeta,
      TCRgammadelta, and EBER. The patient reported a decrease in lesionsize after two
      courses of chemotherapy. However, approximately six months after beginning
      chemotherapy the tumor metastasized to the nasal cavities and brain. This case
      represented another rare systemic ALK-negative ALCL case primarily involving the
      oral cavity.

PMID- 30291890
TI  - Salvianolic acid B as an anti-emphysema agent I: In vitro stimulation of lung
      cell proliferation and migration, and protection against lung cell death, and in
      vivo lung STAT3 activation and VEGF elevation.
AB  - Emphysema causes progressive and life-threatening alveolar structural
      destruction/loss, yet remains irreversible and incurable to date. Impaired
      vascular endothelial growth factor (VEGF) signaling has been proposed as a new
      pathogenic mechanism, and if so, VEGF recovery may enable reversal of emphysema.
      Thus, we hypothesized that salvianolic acid B (Sal-B), a polyphenol in
      traditional Chinese herbal danshen, is an alveolar structural recovery agent for
      emphysema by virtue of VEGF stimulation/elevation via activation of Janus kinase
      2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), as
      stimulating lung cell proliferation and migration, and protecting against lung
      cell death. Using in vitro human lung microvascular endothelial (HMVEC-L) and
      alveolar epithelial (A549) cell systems, Sal-B was examined for 1) stimulation of
      cell proliferation by the MTT and BrdU assays; 2) promotion of cell migration by
      the scratch wound closure assay; 3) protection against emphysema-like induced
      cell death by the trypan blue exclusion and flow cytometry assays; and 4)
      mechanistic involvement of JAK2/STAT3/VEGF in these activities. Sal-B was also
      spray-dosed to the lungs of healthy rats for two weeks to verify the lung's STAT3
      activation and VEGF elevation by western blot, as well as the absence of
      functional and morphological abnormalities. All the in vitro cell-based
      activities were concentration-dependent. At 25 MUM, Sal-B 1) stimulated cell
      proliferation by 1.4-2.6-fold; 2) promoted migratory cell wound closure by 1.5
      1.7-fold; and 3) protected against cell death induced with H2O2 (oxidative
      stress) and SU5416 (VEGF receptor blockade) by 49-86%. JAK2 and STAT3 inhibitors
      and VEGF receptor antagonist each opposed these Sal-B's activities by over 65%,
      suggesting the mechanistic involvement of JAK2/STAT3 activation and VEGF
      stimulation/elevation. In rats, Sal-B at 0.2 mg/kg enabled 1.9 and 1.5-fold
      increased STAT3 phosphorylation and VEGF elevation in the lungs, respectively,
      while causing no functional and morphological abnormalities. Hence, Sal-B was
      projected to be a new class of anti-emphysema agent capable of reversing alveolar
      structural destruction/loss via JAK2/STAT3/VEGF-dependent stimulation of lung
      cell proliferation and migration, and inhibition of induced lung cell death.

PMID- 30291891
TI  - Impairments of emotional face processing in schizophrenia patients: Evidence from
      P100, N170 and P300 ERP components in a sample of auditory hallucinators.
AB  - Patients with schizophrenia show impaired face and emotional expression
      processing that may be due to early perceptual deficits or late impairments in
      higher-order emotional facial recognition. This study examined event-related
      potentials (ERPs) in 23 patients with schizophrenia who experience auditory
      hallucinations and 19 healthy controls. EEG activity was recorded from 32 scalp
      sites positioned according to the 10-10 placement system. Linked left and right
      electrodes at the mastoids served as the reference. The P100, N170 and P300 were
      measured during an emotional facial identification task, which included neutral,
      joyful, sad, angry and fearful facial expressions and non-face stimuli (chairs).
      P100 was measured at O1/2 and P7/8. N170 was measured at P7/8. P300 was measured
      at Pz. Patients with schizophrenia were slower at identifying all facial
      expressions, including neutral ones. They also showed less positive P100
      amplitude to sad, angry and fearful facial expressions. N170 amplitudes were
      smaller in patients in response to neutral, joyful, sad, angry, and fearful
      facial expression. Patients showed less positive P300 mean amplitudes to all
      facial expressions, including neutral ones. Within-group comparisons showed that
      patients exhibited a different pattern of ERP modulation across facial
      expressions than controls for P100 and N170, but not for P300. Our findings are
      compatible with the idea that behavioural and electrophysiological face
      processing deficits in schizophrenia arise from early-stage deficits in visual
      processing.

PMID- 30291892
TI  - Impact of physicochemical properties of DNA/PEI complexes on transient
      transfection of mammalian cells.
AB  - Polyethyleneimine (PEI) has been used extensively for transient gene expression
      (TGE) in mammalian cell cultures. However, the relationship between DNA/PEI
      complex preparation and their biological activity has not been fully established.
      Here, a systematic study of DNA/PEI complexes, their physicochemical properties
      during formation and their transfection efficiency was performed on a virus-like
      particle (VLP) production platform. The same chemically defined cell culture
      medium for DNA/PEI complex formation was used as an alternative to simple ionic
      solutions to minimize changes in complex properties during transfection. Upon
      formation, an initial concentration of 1E + 10 DNA/PEI complexes/mL underwent
      partial aggregation with an average size of 300 nm. The participation of NaCl
      ions in the evolution of complexes was analyzed by X-ray spectroscopy, stressing
      the relevance of complexing media composition in TGE strategies. After 15 min
      incubation, 250 complexes plus aggregates per cell were estimated at the time of
      transfection. Such heterogeneous preparations cannot be easily characterized;
      subsequently, nanoparticle tracking analysis (NTA) and cryo-electron microscopy
      were combined to achieve a complete picture of the preparation. Finally, the
      contribution of each DNA/PEI complex subpopulation was tested by drug inhibition
      endocytosis. Interestingly, all complexes delivered DNA efficiently and high size
      aggregates, which enter through macropinocytosis, when inhibited presented a
      major contribution to transfection efficiency. There is a need to understand the
      physicochemical factors that participate in DNA delivery protocols. Hence, this
      study provides new insights into the characterization of DNA/PEI complexes that
      will assist in more productive and reproducible TGE strategies.

PMID- 30291893
TI  - Are the 2014-2016 Zika and Chikungunya epidemics in Colombia associated with a
      higher use of antihistamines?

PMID- 30291894
TI  - Challenges facing nanotoxicology and nanomedicine due to cellular diversity.
AB  - This review examines the interaction of nanomaterials (NMs) with cells from the
      perspective of major cellular differentiations. The structure and composition of
      cells reflect their role and function in a particular organ or environment. The
      normal differentiated-state and diseased cells may respond to NMs very
      differently. This review progresses with due care on nanotoxicology while
      emphasizing the potential of NMs in treating stress-associated disorders,
      including cancer and degeneration. The striking potential of NMs in inducing ROS,
      scavenging ROS, depleting cellular antioxidants, replenishing antioxidants,
      mimicking antioxidant enzyme activity, and modulating the immune system all show
      their considerable potential in treating cancer and other aging-associated
      disorders. It is now clear that NMs become more active and versatile when they
      come into contact with biological machinery, surprisingly in some cases, in a
      manner dependent on cell type. The mechanisms leading to the contrasting
      bioresponse of NMs ranging from toxicity to anticancer and from cell survival to
      carcinogenicity followed by their immuno-modulating potential show NMs to be a
      highly promising agent in biomedical therapy. This first-of-its-kind article
      seeks the challenges to be addressed that could provide a solid rationale in
      translating the promises of nanomedicine. A thorough understanding of normal and
      cancer biology could help to minimize the gap between basic and translational
      research in nanotechnology-based therapy.

PMID- 30291895
TI  - Sensitivity and colour intensity enhancement in lateral flow immunoassay tests by
      adjustment of test line position.
AB  - In this article, we have enhanced the sensitivity and limit of detection of
      lateral flow immunoassay tests, exemplified for the detection of human chorionic
      gonadotropin (pregnancy) through determination of proper test line position. Test
      line position affects the flow velocity and concentration profile of analytes at
      the test line, which itself impacts the reaction rate and thus the colour
      intensity. The flow velocity was precisely modelled, both analytically and
      numerically, and the predicted analytes' moving front (lateral) velocity was
      experimentally verified. Evolution of the velocity magnitude was determined to
      locate points with proper capillary velocity and accumulated bed-volume. This
      provides insights into the essence of LFIAs performance for simple and easy to
      practice improvements. The colour intensity was measured by quantifying the RGB
      of the resulting test line colours. The response colour intensity was enhanced
      for at least 20%, up to 40% by proper displacement of the test line position, and
      the limit of detection was cut by half to 10 IU/L.

PMID- 30291896
TI  - C-src tyrosine kinase gene rs1378942 polymorphism and hypertension in Asians:
      Review and meta-analysis.
AB  - BACKGROUND: The risk allele frequency of rs1378942 of c-src tyrosine kinase (CSK)
      gene is much higher in Asians (~ 0.80) than that in Europeans (~ 0.35), and the
      association between rs1378942 and blood pressure is controversial in Asians.
      Thus, the review and meta-analysis was performed to explore the effects of
      rs1378942 polymorphism on systolic blood pressure (SBP), diastolic blood pressure
      (DBP) levels and hypertension in Asians. METHODS: A literature search was
      conducted in electronic databases up to September 1, 2018. Beta, Odds Ratio (OR)
      and corresponding 95% confidence intervals (95%CI) were calculated to estimate
      the effects of rs1378942 on SBP, DBP and hypertension. Quanto software was used
      to estimate the statistical power. RESULTS: The results showed that the rs1378942
      polymorphism significantly affected blood pressure levels in Asians, the C allele
      carriers had higher SBP and DBP levels: beta (95%CI): 0.71(0.38-1.04), P = 2.579
      * 10-5, I2 = 43.5%, and beta (95%CI): 0.33(0.18-0.49), P = 2.092 * 10-5, I2 =
      28.3%, respectively. This association was also found in East Asians, but not in
      South Asians. Furthermore, no significant association was observed with
      hypertension: OR (95%CI): 1.10 (0.97-1.25), P = .129, I2 = 81.2%. CONCLUSION: The
      meta-analysis demonstrates that the C allele of the CSK rs1378942 is associated
      with higher SBP and DBP levels in East Asians.

PMID- 30291897
TI  - Protein-based nanoparticles in cancer vaccine development.
AB  - Peptide and protein-based cancer vaccines usually fail to elicit efficient immune
      responses against tumors. However, delivery of these peptides and proteins as
      components within caged protein nanoparticles has shown promising improvements in
      vaccine efficacy. Advantages of protein nanoparticles over other vaccine
      platforms include their highly organized structures and symmetry,
      biodegradability, ability to be specifically functionalized at three different
      interfaces (inside and outside the protein cage, and between subunits in
      macromolecular assembly), and ideal size for vaccine delivery. In this review, we
      discuss different classes of virus-like particles and caged protein nanoparticles
      that have been used as vehicles to transport and increase the interaction of
      cancer vaccine components with the immune system. We review the effectiveness of
      these protein nanoparticles towards inducing and elevating specific immune
      responses, which are needed to overcome the low immunogenicity of the tumor
      microenvironment.

PMID- 30291898
TI  - Inorganic polyphosphate hydrolysis catalyzed by skeletal muscular actomyosin
      complexes is uncoupled with motility.
AB  - Hydrolysis of the triphosphate moiety of ATP, catalyzed by myosin, induces
      alterations in the affinity of the myosin heads for actin filaments via
      conformational changes, thereby causing motility of the actomyosin complexes. To
      elucidate the contribution of the triphosphate group attached to adenosine, we
      examined the enzymatic activity of heavy meromyosin (HMM) with actin filaments
      for inorganic tripolyphosphate (3PP) using a Malachite green method and evaluated
      using fluorescence microscopy the effects of 3PP on actin filament motility on
      HMM-coated glass slides. In the presence of MgCl2, HMM hydrolyzed 3PP at a
      maximum rate of 0.016 s-1 HMM-1, which was four times lower than the hydrolysis
      rate of ATP. Tetrapolyphosphate (4PP) was hydrolyzed at a rate similar to that of
      3PP hydrolysis. The hydrolysis rates of 3PP and 4PP were enhanced by roughly 10
      fold in the presence of actin filaments. In motility assays, the presence of
      polyphosphates did not lead to the sliding movement of actin filaments. Moreover,
      in the presence of ATP at low concentrations, the sliding velocity of actin
      filaments decreased as the concentration of added polyphosphate increased,
      indicating a competitive binding of polyphosphate to myosin heads with ATP. These
      results suggested that the energy produced by standalone triphosphate hydrolysis
      did not induce the unidirectional motion of actomyosin and that the link between
      triphosphate and adenosine was crucial for motility.

PMID- 30291899
TI  - Antithrombotic P2Y12 receptor antagonists: recent developments in drug discovery.
AB  - The P2Y12 receptor is one of eight known P2Y receptor subtypes, and belongs to
      the G-protein-coupled receptor (GPCR) family. The P2Y12 receptor is highly
      expressed on blood platelets and in the brain. Potent, selective, peripherally
      acting antagonists for the P2Y12 receptor are used clinically as antithrombotic
      drugs. Several different scaffolds have been identified as P2Y12 receptor
      antagonists, including irreversibly acting thienotetrahydropyridines (prodrugs),
      and reversible competitive antagonists, including adenine nucleotide analogs,
      piperazinyl-glutamate-quinolines, -pyridines, and -pyrimidines, and anthraquinone
      derivatives. Here, we provide an overview of the different scaffolds that have
      been developed as P2Y12 receptor antagonists, some of which have become important
      therapeutics.

PMID- 30291900
TI  - The future R&D landscape in non-alcoholic steatohepatitis (NASH).
AB  - Nonalcoholic steatohepatitis (NASH) is emerging as a major public health issue
      for the 21st century and is associated with significant liver-related morbidity
      and mortality. At present, there are no approved drug therapies for NASH.
      Consequently, NASH has become the focus of significant public and private
      research and development. In this review, we highlight the research and
      development (R&D) challenges and opportunities in this emerging therapeutic area.
      In particular, we consider the impact of the development of new biomarker
      strategies on clinical trial execution and design, and the positioning of single
      and combination therapies in future approaches to the treatment of NASH.

PMID- 30291901
TI  - First genome sequence of a blaKPC-2-carrying Citrobacter koseri isolate collected
      from a patient with diarrhoea.
AB  - OBJECTIVES: The blaKPC gene is rarely reported in Citrobacter koseri. Here we
      report the first draft genome sequence of a blaKPC-2-carrying C. koseri isolate
      from a patient with diarrhoea. METHODS: Transferability of the blaKPC-2-bearing
      plasmid was determined by the filter mating method. The whole genome sequence of
      C. koseri L168 was determined using an Illumina HiSeq platform. The genome was de
      novo assembled using Velvet 1.2.10. Acquired antimicrobial resistance genes and
      plasmid replicons were identified using ResFinder 2.1 and PlasmidFinder 1.3,
      respectively. RESULTS: Antimicrobial susceptibility testing (AST) showed that C.
      koseri L168 was resistant to multiple antibiotics but was susceptible to
      ciprofloxacin, gentamicin, tobramycin, amikacin, tigecycline and colistin. A KPC
      2-harbouring plasmid was conjugative and the transconjugants conferred increased
      resistance to carbapenems confirmed by conjugation experiments and AST. In silico
      analysis revealed the presence of the beta-lactam resistance genes blaKPC-2 and
      blaMAL-1. Additionally, plasmids of incompatibility groups IncFII and IncX4 were
      identified in the genome by PlasmidFinder. BLAST analysis revealed that blaKPC-2
      was located on a Tn3 transposon element in C. koseri L168 with the conserved
      linear structure ISKpn27-blaKPC-2-DeltaISKpn6-korC-klcA. CONCLUSIONS: To our
      knowledge, this is only the second report of C. koseri producing KPC-2, and we
      report the first draft genome sequence of a blaKPC-2-carrying C. koseri isolate
      from a patient with diarrhoea in China. This work may facilitate our
      understanding of the pathogenesis, multidrug resistance mechanisms and genomic
      features of this species. Further monitoring of bacteria carrying carbapenemase
      genes in patients' gut microbiota is warranted.

PMID- 30291902
TI  - Atopobium vaginae intrapartum bacteremia: A case report with a literature review.
AB  - Atopobium vaginae is an anaerobic Gram-positive bacterium recognized as a
      causative agent of bacterial vaginosis and associated with preterm delivery.
      Invasive infection and bacteremia have been rarely reported. We describe the case
      of a woman expecting her firstborn child who presented with a A. vaginae
      bacteremia during labor. Identification was performed using 16S rRNA gene
      sequencing. Both maternal and fetal outcomes were favorable due to the maternal
      treatment with amoxicillin-clavulanic acid. We identified three other cases in
      the literature with different fetal outcome. The genetic diversity of A. vaginae
      should be further explored in order to reveal potential strains with differential
      pathogenic potential.

PMID- 30291903
TI  - Characterization of the vaginal microbiota of Japanese women.
AB  - The composition of vaginal microbiota changes throughout life in response to
      health status, sexual activity, and pregnancy. Here the constitution of the
      vaginal microbiota among non-pregnant women, pregnant woman, and commercial sex
      workers (CSWs) in Japan were compared. Vaginal samples were obtained from 54
      women between January 2014 and February 2015 and the microbiota of each was
      analyzed by 16S metagenomics as well as cluster and diversity analyses to
      identify differences. In addition, vaginal Lactobacillus spp. were isolated for
      comparison. Furthermore, data regarding the use of ritodrine hydrochloride by
      pregnant women was collected from medical charts. The vaginal microbiota were
      clustered into three groups. Group 1 was most often dominated by Lactobacillus
      spp., whereas groups 2 and 3 included not only Lactobacillus spp. but also
      Bifidobacterium, Atopobium, Prevotella, and Gardnerella spp., in addition to a
      few other taxa. In non-pregnant women, the proportions of microbes in groups 1,
      2, and 3 were 31.8%, 36.4%, and 31.8%, respectively. In pregnant women, the
      abundance of group 1 microbes was notably greater than that of groups 2 and 3
      (66.7% vs. 12.5% and 20.8%, respectively). In CSWs, the prevalence of group 3
      microbes was far greater than that of group 1 (87.5% vs. 12.5%, respectively).
      The alpha diversity of non-pregnant women was significantly greater than that of
      pregnant women. The detection rate of live Lactobacillus spp. in CSWs was lower
      than in pregnant and non-pregnant women (25% vs. 50% and 68.2%, respectively).
      The vaginal microbiota of most pregnant women (60%) who received ritodrine
      hydrochloride was not dominated by Lactobacillus spp. These results suggest that
      there were clear differences in the colonization rate of Lactobacillus spp. among
      non-pregnant, pregnant, and CSW women groups. In addition, the dominance of
      Lactobacillus may influence the risk of preterm birth among women who received
      ritodrine hydrochloride during pregnancy.

PMID- 30291904
TI  - Waiting for a Pediatric Chronic Pain Clinic Evaluation: A Prospective Study
      Characterizing Waiting Times and Symptom Trajectories.
AB  - Chronic pain during childhood is prevalent and costly, but the access to
      interdisciplinary pain care is limited. Studies investigating adults waiting for
      pain clinic evaluation found that symptoms and quality of life deteriorate over
      the waiting period, but little is known about the experience of adolescents.
      Therefore, we aimed to determine wait list times and the longitudinal trends of
      pain and physical, mental, and social health over a 12-week period. In total, 97
      adolescents, aged 10 to 18 years (M = 14.7 years, 82% female), waiting for
      evaluation at an interdisciplinary pediatric pain clinic completed assessments at
      enrollment and at 4-, 8-, and 12-week follow-up. We performed a review of the
      medical record of attendance patterns 12 months later. Twelve adolescents and
      their parents also completed qualitative interviews, describing their experience
      of waiting for evaluation. Wait times averaged 197.5 days (range = 69-758 days)
      from the time of referral to the first-attended appointment, and 86.6% of youths
      completed appointments. Longitudinal repeated measures analyses demonstrated
      little improvement in pain or other domains of functioning over the 12-week
      period. In qualitative interviews, families described anxious anticipation for
      the upcoming appointment, combined with frustration in waiting. Findings
      highlight the need to consider approaches to reduce wait times and provide early
      intervention for youths awaiting pain clinic evaluation. Perspective: This study
      extends the literature on the characteristics and symptom trajectories of
      adolescents during the wait period for interdisciplinary pain clinic evaluation,
      described previously only in adults with chronic pain. Findings demonstrated an
      average wait time of 6.5 months, during which youths' pain and physical and
      social health remained impaired.

PMID- 30291905
TI  - The Effects of Partners' Helping Motivation on Chronic Pain Patients' Functioning
      Over Time.
AB  - To understand when and why the provision of help by a partner of an individual
      with chronic pain (ICP) yields benefits, it is critical, according to self
      determination theory, to consider the extent to which partners' helping responses
      are supportive of the basic psychological needs of the ICP, as well as the
      motivations underlying these helping responses. The present study (N = 141
      couples), spanning 3 measurement moments over 6 months, investigated temporal
      associations between partners' helping motivation, ICPs' psychological needs, and
      ICPs' functioning across time (ie, well-being, psychological distress, and
      disability). Results showed that partners' autonomous or volitional helping
      motivation (time 1) predicted decreases in ICPs' need frustration (time 2) and
      ICPs' need frustration (time 2) predicted increases in ICPs' psychological
      distress (time 3). Further, ICPs' need satisfaction (time 2) predicted increases
      in well-being (time 3) and decreases in psychological distress (time 3). The link
      between need frustration and ICPs' well-being (time 1-time 2) was bidirectional,
      with both relating reciprocally to one another over time. Finally, the
      associations between ICPs' disability and both partners' helping motivation and
      ICPs' need-based experiences were nonsignificant. Implications for research and
      clinical practice are discussed. Perspective: Partners' helping motivations and
      ICPs' psychological needs seem to be important to consider when investigating the
      role of spousal responses, because they could (indirectly) predict changes in the
      well-being and psychological distress of ICPs over time.

PMID- 30291906
TI  - Endothelins in inflammatory neurological diseases.
AB  - Endothelins were discovered more than thirty years ago as potent vasoactive
      compounds. Beyond their well-documented cardiovascular properties, however, the
      contributions of the endothelin pathway have been demonstrated in several
      neuroinflammatory processes and the peptides have been reported as clinically
      relevant biomarkers in neurodegenerative diseases. Several studies report that
      endothelin-1 significantly contributes to the progression of neuroinflammatory
      processes, particularly during infections in the central nervous system (CNS),
      and is associated with a loss of endothelial integrity at the blood brain barrier
      level. Because of the paucity of clinical trials with endothelin-1 antagonists in
      several infectious and non-infectious neuroinflammatory diseases, it remains an
      open question whether the 21 amino acid peptide is a mediator/modulator rather
      than a biomarker of the progression of neurodegeneration. This review focuses on
      the potential roles of endothelins in the pathology of neuroinflammatory
      processes, including infectious diseases of viral, bacterial or parasitic origin
      in which the synthesis of endothelins or its pharmacology have been investigated
      from the cell to the bedside in several cases, as well as in non-infectious
      inflammatory processes such as neurodegenerative disorders like Alzheimers
      Disease or central nervous system vasculitis.

PMID- 30291907
TI  - Fighting against depression with TREK-1 blockers: Past and future. A focus on
      spadin.
AB  - Depression is a devastating mood disorder and a leading cause of disability
      worldwide. Depression affects approximately one in five individuals in the world
      and represents heavy economic and social burdens. The neurobiological mechanisms
      of depression are not fully understood, but evidence highlights the role of
      monoamine neurotransmitter balance. Several antidepressants (ADs) are marketed to
      treat depression and related mood disorders. However, despite their efficacy,
      they remain nonspecific and unsafe because they trigger serious adverse effects.
      Therefore, developing new molecules for new targets in depression has become a
      real necessity. Eight years ago, spadin was described as a natural peptide with
      AD properties. This 17-amino acid peptide blocks TREK-1 channels, an original
      target in depression. Compared to the classical AD drugs such as fluoxetine,
      which requires 3-4 weeks for the AD effect to manifest, spadin acts rapidly
      within only 4 days of treatment. The AD properties are associated with increased
      neurogenesis and synaptogenesis in the brain. Despite the advantages of this fast
      acting AD, the in vivo stability is weak and does not last for >7 h. The present
      review summarizes different strategies such as retro-inverso strategy,
      cyclization, and shortening the spadin sequence that has led to the development
      and optimization of spadin as an AD. Shortened spadin analogs present increased
      inhibition potency for TREK-1, an improved AD activity, and prolonged in vivo
      bioavailability. Finally, we also discuss about other inhibitors of TREK-1
      channels with a proven efficacy in treating depression in the clinic, such as
      fluoxetine.

PMID- 30291908
TI  - Acetylcholine signaling system in progression of lung cancers.
AB  - The neurotransmitter acetylcholine (ACh) acts as an autocrine growth factor for
      human lung cancer. Several lines of evidence show that lung cancer cells express
      all of the proteins required for the uptake of choline (choline transporter 1,
      choline transporter-like proteins) synthesis of ACh (choline acetyltransferase,
      carnitine acetyltransferase), transport of ACh (vesicular acetylcholine
      transport, OCTs, OCTNs) and degradation of ACh (acetylcholinesterase,
      butyrylcholinesterase). The released ACh binds back to nicotinic (nAChRs) and
      muscarinic receptors on lung cancer cells to accelerate their proliferation,
      migration and invasion. Out of all components of the cholinergic pathway, the
      nAChR-signaling has been studied the most intensely. The reason for this trend is
      due to genome-wide data studies showing that nicotinic receptor subtypes are
      involved in lung cancer risk, the relationship between cigarette smoke and lung
      cancer risk as well as the rising popularity of electronic cigarettes considered
      by many as a "safe" alternative to smoking. There are a small number of articles
      which review the contribution of the other cholinergic proteins in the
      pathophysiology of lung cancer. The primary objective of this review article is
      to discuss the function of the acetylcholine-signaling proteins in the
      progression of lung cancer. The investigation of the role of cholinergic network
      in lung cancer will pave the way to novel molecular targets and drugs in this
      lethal malignancy.

PMID- 30291909
TI  - Increased Mortality Among Patients With vs Without Cirrhosis and Autoimmune
      Hepatitis.
AB  - BACKGROUND & AIMS: There have been few reproducible studies of mortality in
      patients with autoimmune hepatitis (AIH) and its variants. We calculated
      mortality in a large national cohort of patients with AIH, with vs without
      cirrhosis, in the Netherlands. METHODS: We collected data from 449 patients with
      established AIH (77% female), from 6 academic and 10 non-academic hospitals in
      the Netherlands. We identified 29 patients with AIH and primary biliary
      cholangitis and 35 patients with AIH and primary sclerosing cholangitis (AIH
      PSC). Mortality and liver transplantation data were assessed from August 1, 2006
      through July 31, 2016. Standardized mortality ratios (SMR) were calculated using
      age-, sex-, and calendar year-matched mortality for the general Dutch population.
      RESULTS: During the 10-year follow-up period, 60 patients (13%) died (mean age,
      71 years; range, 33-94 years). Twenty-six causes of death were liver related
      (43%), whereas the others could not be attributed to liver disease. Patients with
      AIH and cirrhosis had significantly higher mortality than the general population
      (SMR, 1.9; 95% CI, 1.2-3.4), whereas patients without cirrhosis did not (SMR,
      1.2; 95% CI, 0.8-1.8). Patients with AIH-PSC had the largest increase in
      mortality, compared to the general population (SMR, 4.7; 95% CI, 1.5-14.6), of
      all groups analyzed. Mortality in patients with AIH and primary biliary
      cholangitis was not greater than the general population. Four or more relapses
      per decade or not achieving remission was associated with an increase in liver
      related death or liver transplantation. Nine patients underwent liver
      transplantation; 2 died from non-liver related causes. Four of 9 patients on the
      waitlist for transplantation died before receiving a donated liver. CONCLUSION:
      In an analysis of data from a large national cohort of patients with AIH, we
      found increased mortality of patients with cirrhosis, but not of patients without
      cirrhosis, compared to the general Dutch population. Survival was significantly
      reduced in patients with AIH and features of concurrent PSC.

PMID- 30291910
TI  - No Change in Determining Crohn's Disease Recurrence or Need for Endoscopic or
      Surgical Intervention With Modification of the Rutgeerts Scoring System.
AB  - The postoperative endoscopic recurrence score, commonly referred to as the
      Rutgeerts score, was designed to predict clinical recurrence risk in Crohn's
      disease (CD) patients undergoing ileocolonic resection based on early endoscopic
      findings at the anastomosis and in the neoterminal ileum.1 In the pivotal
      publication, the i2 category, including aphthous lesions in the terminal ileum as
      well as ileocolonic anastomosis lesions, had a heterogeneous recurrence risk.
      Because anastomotic ulcers were suspected to be postsurgical ischemic lesions and
      less predictive of progressive disease,2 a modified Rutgeerts score (mRS) was
      proposed: i2a, lesions confined to the anastomosis +/-<5 isolated aphthous ulcers
      in the ileum; i2b, more than 5 aphthous ulcers in the ileum with normal mucosa in
      between, +/- anastomotic lesions.3,4.

PMID- 30291911
TI  - Augmentation of NAD+ levels by enzymatic action of NAD(P)H quinone oxidoreductase
      1 attenuates adriamycin-induced cardiac dysfunction in mice.
AB  - BACKGROUND: Adriamycin (ADR) is a powerful chemotherapeutic agent extensively
      used to treat various human neoplasms. However, its clinical utility is hampered
      due to severe adverse side effects i.e. cardiotoxicity and heart failure. ADR
      induced cardiomyopathy (AIC) has been reported to be caused by myocardial damage
      and dysfunction through oxidative stress, DNA damage, and inflammatory responses.
      Nonetheless, the remedies for AIC are even not established. Therefore, we
      illustrate the role of NAD+/NADH modulation by NAD(P)H quinone oxidoreductase 1
      (NQO1) enzymatic action on AIC. METHODS AND RESULTS: AIC was established by
      intraperitoneal injection of ADR in C57BL/6 wild-type (WT) and NQO1 knockout
      (NQO1-/-) mice. All Mice were orally administered dunnione (named NQO1 substrate)
      before and after exposure to ADR. Cardiac biomarker levels in the plasma, cardiac
      dysfunction, oxidative biomarkers, and mRNA and protein levels of pro
      inflammatory mediators were determined compared the cardiac toxicity of each
      experimental group. All biomarkers of Cardiac damage and oxidative stress, and
      mRNA levels of pro-inflammatory cytokines including cardiac dysfunction were
      increased in ADR-treated both WT and NQO1-/- mice. However, this increase was
      significantly reduced by dunnione in WT, but not in NQO1-/- mice. In addition, a
      decrease in SIRT1 activity due to a reduction in the NAD+/NADH ratio by PARP-1
      hyperactivation was associated with AIC through increased nuclear factor (NF)
      kappaB p65 and p53 acetylation in both WT and NQO1-/- mice. While an elevation in
      NAD+/NADH ratio via NQO1 enzymatic action using dunnione recovered SIRT1 activity
      and subsequently deacetylated NF-kappaB p65 and p53, however not in NQO1-/- mice,
      thereby attenuating AIC. CONCLUSION: Thus, modulation of NAD+/NADH by NQO1 may be
      a novel therapeutic approach to prevent chemotherapy-associated heart failure,
      including AIC.

PMID- 30291912
TI  - 11beta-hydroxysteroid dehydrogenase type 1 inhibitor attenuates high-fat diet
      induced cardiomyopathy.
AB  - BACKGROUND: High-fat diet (HFD) induces cardiac hypertrophy; however, the
      underlying cellular and molecular mechanisms are yet unclear. In the present
      study, we investigated the roles of 11beta-hydroxysteroid dehydrogenase type 1
      (11beta-HSD1), an amplifier of local glucocorticoid activity, in the pathogenesis
      of cardiac dysfunction. METHODS: Male Wistar rats were fed normal chow diet (NC)
      or HFD and examined the cardiac remolding and functional alteration by
      echocardiography and histology. Primary neonatal rat ventricular cardiomyocytes
      (NRCMs) treated with palmitic acid (PA) or infected by lentivirus were used for
      identifying the role by 11beta-HSD1 in cardiac hypertrophy. Genome microarray of
      NRCMs was performed to further reveal the mechanism underlying cardiac
      dysfunction. RESULTS: Palmitic acid induced hypertrophy in NRCMs that upregulated
      11beta-HSD1 expression in cardiomyocytes, which led to a significant enlargement
      in the cell size and expression of cardiac hypertrophy-specific genes.
      Conversely, a remarkable decrease in cardiomyocytes size was detected in either
      BVT.2733 (a selective inhibitor of 11beta-HSD1)-treated or 11beta-HSD1-deficient
      NRCMs. Furthermore, both glucocorticoid receptor (GR) antagonist RU486 and
      mineralocorticoid receptor (MR) antagonist spironolactone markedly attenuated the
      11beta-HSD1-induced cardiomyocytes hypertrophy. Genome microarray revealed that
      cAMP and calcium signaling pathways are potential downstream signaling pathways
      regulated by 11beta-HSD1 in cardiomyocytes hypertrophy. Similar to in vitro
      results, BVT.2733 strikingly attenuated cardiac hypertrophy and improved cardiac
      function in HFD-fed rats. CONCLUSION: 11beta-HSD1 acts as an important regulator
      that controls the cardiac remolding via both GR and MR and the pharmacological
      inhibition of 11beta-HSD1 could be a new therapeutic approach in preventing HFD
      induced cardiac hypertrophy.

PMID- 30291913
TI  - Comparative Genomic Profiling of Refractory/Metastatic Penile and non-Penile
      Cutaneous Squamous Cell Carcinoma: Implications for Selection of Systemic
      Therapy.
AB  - BACKGROUND: Metastatic penile squamous cell carcinoma (mPSCC) is an aggressive
      malignancy with limited treatment options. We compared the potential therapy
      impacting genomic alterations (GA) between mPSCC and non-penile cutaneous
      metastatic squamous cell carcinoma (mCSCC). METHODS: DNA was extracted from 40
      microns of FFPE samples from 78 cases of mPSCC and 338 mCSCC. Comprehensive
      genomic profiling (CGP), was performed using a hybrid-capture, adaptor ligation
      based next generation sequencing assay to a mean coverage depth of >500X. Tumor
      mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and
      microsatellite instability (MSI) was determined on 114 loci. RESULTS: Potential
      targeted therapy opportunities in mPSCC included alterations in MTOR pathway (NF1
      GA in 7% and PTEN GA in 4%) and DNA repair pathway (BRCA2 and ATM GA, each in 7%)
      and tyrosine kinase (EGFR GA in 6%; FGFR3 and ERBB2 GA each in 4%). TMB was
      significantly higher in the predominantly UV light exposed mSCC than mPSCC,
      making mSCC potentially more responsive to immunotherapies than mPSCC. MSI-High
      status was extremely rare for both mPSCC and mCSCC. CD274 (PD-L1) amplification
      was also rare in both tumor types. CONCLUSIONS: mPSCC is a unique subtype of SCC
      with distinctive genomic features that contrast with those identified in mCSCC of
      non-penile UV light exposed skin. Although not rich in predictors for response to
      immunotherapy (low TMB and MSI low), more than one quarter of mPSCC may
      potentially benefit from existing and available therapies targeting MTOR, DNA
      repair, and Tyrosine Kinase pathways.

PMID- 30291914
TI  - Can We Predict Functional Outcomes after Partial Nephrectomy?
AB  - PURPOSE: Percent parenchymal mass-preserved (PPMP) is the primary determinant of
      functional outcomes after partial nephrectomy (PN). Accurate methods for
      predicting PPMP based on preoperative imaging could facilitate patient
      counseling. MATERIALS/METHODS: 428 PN patients with necessary studies to assess
      ipsilateral parenchymal mass/function preserved were evaluated.
      Preoperative/postoperative ipsilateral parenchymal mass were measured from
      contrast-enhanced CT<2 months prior and 3-12 months after PN and actual-PPMP was
      determined. Ipsilateral-PPMP and final global-GFR were estimated based on
      preoperative imaging using subjective estimation (SE), quantitative estimation
      (QE), or estimation derived from contact surface area (CSA) or R.E.N.A.L.
      RESULTS: Median tumor diameter was 3.5cm. Median CSA/R.E.N.A.L. were 24cm2 and 8,
      respectively. Median actual ipsilateral-PPMP and percent global-GFR preserved
      were 84%/89%, respectively. Median estimated ipsilateral-PPMP was 85%/87%/88%/83%
      based on SE/QE/CSA/R.E.N.A.L., respectively. Correlations between actual-PPMP and
      estimated-PPMP were relatively weak in all instances, (all r<=0.46). Prediction
      of final global-GFR was strong for all 4 methods (all r=0.91); however, similarly
      strong correlation was also obtained when presuming that 89% of the preoperative
      global-GFR will be saved in each case (r=0.91). On multivariable analyses,
      solitary-kidney, preoperative-GFR, and various estimates of PPMP significantly
      associated with final global-GFR. However, preoperative-GFR proved to be the
      strongest predictor; it was >10-fold more impactful than estimated-PPMP or
      solitary-kidney. CONCLUSIONS: Currently available methods for estimating PPMP
      have important limitations. Final global-GFR, the most important functional
      outcome, can be predicted fairly accurately by all of the tested methods but none
      are better than simply presuming that 89% of function will be saved, due to
      strong anchoring to preoperative-GFR.

PMID- 30291915
TI  - The changing epidemiology of ventricular arrhythmias and sudden cardiac death: Is
      it a reality?

PMID- 30291916
TI  - Native T1 mapping as a biomarker of underlying ventricular myopathy and its
      reversal in patients with atrial fibrillation and preserved ejection fraction
      undergoing catheter ablation.

PMID- 30291917
TI  - Major ecological shifts within the dominant nonstarter lactic acid bacteria in
      mature Greek Graviera cheese as affected by the starter culture type.
AB  - Traditional Greek Graviera cheese is often produced from thermized milk to
      control undesirable bacterial contaminants. Since thermization also reduces the
      desirable lactic acid bacteria (LAB) microbiota of raw milk, natural undefined or
      commercially defined starters are used. This study evaluated effects of the type
      of starter added to bulk thermized milk on the microbiology of mature (day-90)
      Graviera cheese. Cheeses produced with a natural starter culture (NSC) in non
      concentrated yogurt-like form or a commercial starter culture (CSC) containing
      Streptococcus thermophilus and various Lactococcus lactis strains in concentrated
      freeze-dried form, were analyzed microbiologically, and 200 LAB isolates (100
      from each type of cheese) were identified. The LAB microbiota of the mature CSC
      cheeses was dominated by nonstarter strains of Lactobacillus paracasei and Lb.
      plantarum whereas indigenous Enterococcus faecium and E. durans strains of high
      phenotypic and genotypic diversity predominated in the respective NSC-cheeses.
      Populations of enterococci in CSC-cheeses were subdominant by 10 to 100-fold
      compared with those in NSC-cheeses; E. faecium was the most frequently isolated
      Enterococcus species from the mature CSC-cheeses. Sporadic or no isolates of
      other LAB species, including the commercial S. thermophilus and Lc. lactis
      starter strains in the CSC-cheeses and the natural S. thermophilus and
      Lactobacillus delbrueckii subsp. bulgaricus starter strains plus indigenous
      Lactococcus, Leuconostoc and E. faecalis in the NSC-cheeses, were detected. In
      conclusion, the replacement of the NSC with the CSC controlled growth of dairy
      enterococci in favor of mesophilic nonstarter lactobacilli during ripening. While
      safety concerns associated with the inefficiency of NSCs to prevent outgrowth of
      indigenous enterococci suggest that CSCs should be preferred by traditional Greek
      Graviera cheese processors, panel sensory evaluations showed that the NSC-ripened
      cheeses were of slightly lower appearance but of occasionally higher flavor
      scores than the CSC-ripened cheeses.

PMID- 30291918
TI  - Effect of different font sizes and of spaces between words on eye movement
      performance: An eye tracker study in dyslexic and non-dyslexic children.
AB  - The aim of the present study was to explore the possible change in eye movement
      performance in a group of dyslexic and non-dyslexic children reading four lines
      of a text with different font sizes and spaces between the words. Fifteen
      dyslexic children from 7 to 12 years old and two groups of fifteen non-dyslexic
      children, respectively reading and chronological age-matched group, participated
      in this study. Horizontal eye movements from both eyes were recorded by a video
      system (EyeBrain T2(r)) while the children were reading a text. Three different
      texts were used with different font sizes and spaces between words. Results
      showed that increasing font size and character spacing significantly reduced
      duration of the fixation and increased the number and amplitude of prosaccades in
      all groups of children tested. Interestingly, while reading texts in which the
      letters were larger and more spaced (Texts 2 and 3), the duration of fixations in
      dyslexic and in non-dyslexic children groups decreased, becoming similar to those
      reported in the non-dyslexic children group. We suggest that large letter spacing
      between words could be employed in schools to help dyslexic children in order to
      ameliorate their reading performance.

PMID- 30291919
TI  - These are the people in your neighbourhood: Consistency and persistence in
      infants' exposure to caregivers', relatives', and strangers' faces across
      contexts.
AB  - Faces are a frequent part of young infants' visual environments. Three-month-old
      infants spend approximately 25% of their time exposed to faces (Sugden, Mohamed
      Ali, & Moulson, 2014; Jayaraman, Fausey, & Smith, 2015). These faces belong
      primarily to familiar people, like their caregivers, and are heavily weighted
      towards female, adult-aged, and own-race faces. To date, descriptions of infants'
      exposure to faces have focused on frequency-both overall frequency and relative
      frequency of different face types (e.g., familiar vs. unfamiliar; own-race vs.
      other-race). It is less clear whether faces of different types distinguish
      themselves in other ways that have implications for infants' learning. Here, we
      move beyond an evaluation of frequency to determine the dimensions by which
      familiar faces (i.e., caregivers and relatives, as identified by parental report)
      differentiate themselves from unfamiliar (i.e., stranger's) faces in the infant's
      early visual environment. Measuring infants' natural visual ecology with head
      mounted infant-perspective cameras, we found that 3-month-olds were exposed to
      faces 21% of the time. The primary caregiver was the most frequent face (44% of
      exposure time) and non-primary caregivers were often second most frequent (17% of
      exposure time). Caregiver faces also distinguished themselves by their
      consistency across both contexts and time. For example, the primary caregiver's
      face was most likely to appear across contexts and locations. Primary caregiver
      faces were less likely to persist in the field of view, as compared to non
      primary caregiver and stranger faces. Thus, the socially important faces in the
      infant's visual environment distinguish themselves not only through their overall
      frequency, but also through their consistency across contexts. This has
      implications for understanding how the early visual environment shapes learning
      about faces.

PMID- 30291920
TI  - Estimates of edge detection filters in human vision.
AB  - Edge detection is widely believed to be an important early stage in human visual
      processing. However, there have been relatively few attempts to map human edge
      detection filters. In this study, observers had to locate a randomly placed step
      edge in brown noise (the integral of white noise) with a 1/f2 power spectrum.
      Their responses were modelled by assuming the probability the observer chose an
      edge location depended on the response of their own edge detection filter to that
      location. The observer's edge detection filter was then estimated by maximum
      likelihood methods. The filters obtained were odd-symmetric and similar to a
      derivative of Gaussian, with a peak-to-trough width of 0.1-0.15 degrees. These
      filters are compared with previous estimates of edge detectors in humans, and
      with neurophysiological receptive fields and theoretical edge detectors.

PMID- 30291921
TI  - pH dependent membrane binding of the Solanum tuberosum plant specific insert: An
      in silico study.
AB  - The Solanum tuberosum plant-specific insert (StPSI) has been shown to possess
      potent antimicrobial activity against both human and plant pathogens.
      Furthermore, in vitro, the StPSI is capable of fusing phospholipid vesicles,
      provided the conditions of net anionic vesicle charge and acidic pH are met.
      Constant pH replica-exchange simulations indicate several acidic residues on the
      dimer have highly perturbed pKas (<3.0; E15, D28, E85 & E100) due to involvement
      in salt bridges. After setting the pH of the system to either 3.0 or 7.4, all
      atom simulations provided details of the effect of pH on secondary structural
      elements, particularly in the previously unresolved crystallographic structure of
      the loop section. Coarse-grained dimer-bilayer simulations demonstrated that at
      pH 7.4, the dimer had no affinity for neutral or anionic membranes over the
      course of 1 MUs simulations. Conversely, at pH 3.0 two binding modes were
      observed. Mode 1 is mediated primarily via strong N-terminal interactions on one
      monomer only, whereas in mode 2, N- and C-terminal residues of one monomer and
      numerous polar and basic residues on the second monomer, particularly in the
      third helix, participate in membrane interactions. Mode 2 was accompanied by re
      orientation of the dimer to a more vertical position with respect to helices 1
      and 4, positioning the dimer for membrane interactions. These results offer the
      first examination at near-atomic resolution of residues mediating the StPSI
      membrane interactions, and allow for the postulation of a possible fusion
      mechanism.

PMID- 30291922
TI  - VDAC electronics: 5. Mechanism and computational model of hexokinase-dependent
      generation of the outer membrane potential in brain mitochondria.
AB  - Glycolysis plays a key role in brain energy metabolism. The initial and rate
      limiting step of brain glycolysis is catalyzed mainly by hexokinase I (HKI), the
      majority of which is bound to the mitochondrial outer membrane (MOM), mostly
      through the mitochondrial inter-membrane contact sites formed by the voltage
      dependent anion channel (VDAC, outer membrane) and the adenine nucleotide
      translocator (ANT, inner membrane). Earlier, we proposed a mechanism for the
      generation of the mitochondrial outer membrane potential (OMP) as a result of
      partial application of the inner membrane potential (IMP) to MOM through the
      electrogenic ANT-VDAC-HK inter-membrane contact sites. According to this previous
      mechanism, the Gibbs free energy of the hexokinase reaction might modulate the
      generated OMP (Lemeshko, Biophys. J., 2002). In the present work, a new
      computational model was developed to perform thermodynamic estimations of the
      proposed mechanism of IMP-HKI-mediated generation of OMP. The calculated OMP was
      high enough to electrically regulate MOM permeability for negatively charged
      metabolites through free, unbound VDACs in MOM. On the other hand, the positive
      inside polarity of OMP generated by the IMP-HKI-mediated mechanism is expected to
      protect mitochondria against elevated concentrations of cytosolic Ca2+. This
      computational analysis suggests that metabolically-dependent generation of OMP in
      the brain mitochondria, controlled by many factors that modulate VDAC1-HKI
      interaction, VDAC's voltage-gating properties and permeability, might represent
      one of the physiological mechanisms of regulation of the brain energy metabolism
      and of neuronal death resistance, and might also be involved in various
      neurodegenerative disorders, such as Alzheimer's disease.

PMID- 30291923
TI  - Acylation of the S413-PV cell-penetrating peptide as a means of enhancing its
      capacity to mediate nucleic acid delivery: Relevance of peptide/lipid
      interactions.
AB  - BACKGROUND: Cell-penetrating peptides (CPPs) have been extensively exploited in
      gene therapy approaches as vectors for intracellular delivery of bioactive
      molecules. The ability of CPPs to be internalized into cells and their capacity
      to complex nucleic acids depend on their molecular structure, both primary and
      secondary, namely regarding hydrophobicity/hydrophilicity. CPP acylation has been
      used as a strategy to improve this structural feature. METHODS: Acyl groups (from
      6 to 18 carbon atoms) were attached to the S413-PV peptide and their effects on
      the peptide competence to complex siRNAs and to mediate gene silencing in
      glioblastoma (GBM) cells were studied. A systematic characterization of membrane
      interactions with S413-PV acyl-derivatives was also conducted, using different
      biophysical techniques (surface pressure-area isotherms in Langmuir monolayers,
      DSC and 31P NMR) to unravel a relationship between CPP biological activity and
      CPP effects on membrane stability and lipid organization. RESULTS: A remarkable
      concordance was noticed between acylated-S413-PV peptide competence to promote
      gene silencing in GBM cells and disturbance induced in membrane models, the
      lauroyl- and myristoyl-S413-PV peptides being the most effective. A cut-off
      effect was described for the first time regarding the influence of acyl-chain
      length on CPP bioactivity. CONCLUSIONS: C12-S413-PV showed high capacity to
      destabilize lipid bilayers, to escape from lysosomal degradation and to mediate
      gene silencing without promoting cytotoxicity. GENERAL SIGNIFICANCE: Besides
      unraveling a new CPP with high potential to be employed as a gene delivery
      vector, this work emphasizes the benefit from allying biophysical and biological
      studies towards a proper CPP structural refinement for successful pre
      clinical/clinical application.

PMID- 30291924
TI  - Lipid bilayers cushioned with polyelectrolyte-based films on doped silicon
      surfaces.
AB  - Silicon semiconductors with a thin surface layer of silica were first modified
      with polyelectrolytes (polyethyleneimine, polystyrene sulfonate and
      poly(allylamine)) via a facile layer-by-layer deposition approach. Subsequently,
      lipid vesicles were added to the preformed polymeric cushion, resulting in the
      adsorption of intact vesicles or fusion and lipid bilayer formation. To study
      involved interactions we employed optical reflectometry, electrochemical
      impedance spectroscopy and fluorescent recovery after photobleaching. Three
      phospholipids with different charge of polar head groups, i.e. 1,2-dioleoyl-sn
      glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-sn-glycero-3-phospho-l-serine
      (DOPS) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were used to prepare
      vesicles with varying surface charge. We observed that only lipid vesicles
      composed from 1:1 (mole:mole) mixture of DOPC/DOPS have the ability to fuse onto
      an oppositely charged terminal layer of polyelectrolyte giving a lipid bilayer
      with a resistance of >100 kOmega. With optical reflectometry we found that the
      vesicle surface charge is directly related to the amount of mass adsorbed onto
      the surface. An interesting observation was that zwitterionic polar head groups
      of DOPC allow the adsorption on both positively and negatively charged surfaces.
      As found with fluorescent recovery after photobleaching, positively charged
      surface governed by the presence of poly(allylamine) as the terminal layer
      resulted in intact DOPC lipid vesicles adsorption whereas in the case of a
      negatively charged silica surface formation of lipid bilayers was observed, as
      expected from literature.

PMID- 30291925
TI  - Chest CT Scan at Radiation Dose of a Posteroanterior and Lateral Chest Radiograph
      Series: A Proof of Principle in Lymphangioleiomyomatosis.
AB  - BACKGROUND: Given the rising utilization of medical imaging and the risks of
      radiation, there is increased interest in reducing radiation exposure. The
      objective of this study was to evaluate, as a proof of principle, CT scans
      performed at radiation doses equivalent to that of a posteroanterior and lateral
      chest radiograph series in the cystic lung disease lymphangioleiomyomatosis.
      METHODS: From November 2016 to May 2018, 105 consecutive subjects with
      lymphangioleiomyomatosis received chest CT scans at standard and ultra-low
      radiation doses. Standard and ultra-low dose images, respectively, were
      reconstructed with routine iterative and newer model-based iterative
      reconstruction. Lymphangioleiomyomatosis severity can be quantified as cyst score
      (percentage of lung occupied by cysts), an ideal benchmark for validating CT
      scans performed at a reduced dose compared with a standard dose. Cyst scores were
      quantified using semi-automated software and evaluated by linear correlation and
      Bland-Altman analysis. RESULTS: Overall, ultra-low dose CT scans represented a
      96% dose reduction, with a median dose equivalent to 1 vs 22 posteroanterior and
      lateral chest radiograph series (0.14 mSv; 5th-95th percentile, 0.10-0.20 vs
      standard dose 3.4 mSv; 5th-95th percentile, 1.5-7.4; P < .0001). The mean
      difference in cyst scores between ultra-low and standard dose CT scans was 1.1%
      +/- 2.0%, with a relative difference in cyst score of 11%. Linear correlation
      coefficient was excellent at 0.97 (P < .0001). CONCLUSIONS: In
      lymphangioleiomyomatosis, chest CT scan at substantial radiation reduction to
      doses equivalent to that of a posteroanterior and lateral chest radiograph series
      provides similar cyst score quantification as standard dose CT scan. TRIAL
      REGISTRY: ClinicalTrials.gov; Nos.: NCT00001465 and NCT00001532; URL:
      www.clinicaltrials.gov.

PMID- 30291926
TI  - Building a Prediction Model for Radiographically Confirmed Pneumonia in Peruvian
      Children: From Symptoms to Imaging.
AB  - BACKGROUND: Community-acquired pneumonia remains the leading cause of death in
      children worldwide, and current diagnostic guidelines in resource-poor settings
      are neither sensitive nor specific. We sought to determine the ability to
      correctly diagnose radiographically confirmed clinical pneumonia when diagnostics
      tools were added to clinical signs and symptoms in a cohort of children with
      acute respiratory illnesses in Peru. METHODS: Children < 5 years of age with an
      acute respiratory illness presenting to a tertiary hospital in Lima, Peru, were
      enrolled. The ability to predict radiographically confirmed clinical pneumonia
      was assessed using logistic regression under four additive scenarios: clinical
      signs and symptoms only, addition of lung auscultation, addition of oxyhemoglobin
      saturation (Spo2), and addition of lung ultrasound. RESULTS: Of 832 children
      (mean age, 21.3 months; 59% boys), 453 (54.6%) had clinical pneumonia and 221
      (26.6%) were radiographically confirmed. Children with radiographically confirmed
      clinical pneumonia had lower average Spo2 than those without (95.9% vs 96.6%,
      respectively; P < .01). The ability to correctly identify radiographically
      confirmed clinical pneumonia using clinical signs and symptoms was limited (area
      under the curve [AUC] = 0.62; 95% CI, 0.58-0.67) with a sensitivity of 66% (95%
      CI, 59%-73%) and specificity of 53% (95% CI, 49%-57%). The addition of lung
      auscultation improved classification (AUC = 0.73; 95% CI, 0.69-0.77) with a
      sensitivity of 75% (95% CI, 69%-81%) and specificity of 53% (95% CI, 49%-57%) for
      the presence of crackles. In contrast, the addition of Spo2 did not improve
      classification (AUC = 0.73; 95% CI, 0.69-0.77) with a sensitivity of 40% (95% CI,
      33%-47%) and specificity of 72% (95% CI, 68%-75%) for an Spo2 <= 92%. Adding
      consolidation on lung ultrasound was associated with the largest improvement in
      classification (AUC = 0.85; 95% CI, 0.82-0.89) with a sensitivity of 55% (95% CI,
      48%-63%) and specificity of 95% (95% CI, 93%-97%). CONCLUSIONS: The addition of
      lung ultrasound and auscultation to clinical signs and symptoms improved the
      ability to correctly classify radiographically confirmed clinical pneumonia.
      Implementation of auscultation- and ultrasound-based diagnostic tools can be
      considered to improve diagnostic yield of pneumonia in resource-poor settings.

PMID- 30291928
TI  - Controlled release of cephradine by biopolymers based target specific crosslinked
      hydrogels.
AB  - The novel silane crosslinked (TEOS) hydrogels based on eco-friendly biodegradable
      chitosan/guargum were prepared by blending with PEG to develop pH sensitive
      hydrogels (CGP) and achieved its hydrophilicity and target specificity for
      controlled release of drug. The crosslinker amount was varied to analyze its
      effect on the hydrogel properties and were characterized using FTIR, SEM, TGA,
      swelling studies (water, buffer and ionic solution) and in-vitro release of
      cephradine (CED). FTIR confirmed the presence of characteristic peaks and
      crosslinking between the components while SEM images showed the formation of
      clear micro- and macro-pores. The swelling behavior in water showed that compared
      to the controlled hydrogel, the crosslinked hydrogels revealed more swelling but
      a decrease in swelling with further increase in the amount of crosslinker was
      observed. The hydrogels showed low swelling at basic and neutral pH while maximum
      swelling was observed at acidic pH. This pH response made these hydrogels an
      ideal candidate for injectable controlled release. The CED was loaded on
      hydrogels and its release mechanism was studied in PBS, SGF and SIF which
      revealed that out of all hydrogels (CGP100, CGP150, CGP200 and CGP250), CGP100
      has shown CED release of 85% in 130 min in PBS and 82.4% in SIF.

PMID- 30291929
TI  - Physiochemical characteristics and bone/cartilage tissue engineering
      potentialities of protein-based macromolecules - A review.
AB  - Protein-based macromolecules such as keratin, silk fibroin, collagen, gelatin,
      and fibrin have emerged as potential candidate materials with unique structural
      and functional characteristics. Despite many advantages, the development of
      tissue-engineered constructs that can match the biological context of real tissue
      matrix remains a challenge in tissue engineering (TE). The tissue-engineered
      constructs should also support vascularization. Protein-based macromolecules, in
      pristine or combine form, provide a promising platform to engineer constructs
      with unique design and functionalities which are highly essential for an
      appropriate stimulation and differentiation of cells in a specific TE approach.
      However, much work remains to be undertaken with particular reference to in-depth
      interactions between constructed cues and target host tissues. Thus, modern
      advancements are emphasizing to understand critiques and functionalization of
      protein-based macromolecule that organize not only cellular activities but also
      tissue regenerations. In this review, numerous physicochemical, functional, and
      structural characteristics of protein-based macromolecules such as keratin, silk
      fibroin, collagen, gelatin, and fibrin are discussed. This review also presents
      the hope vs. hype phenomenon for tissue engineering. Later part of the review
      focuses on different requisite characteristics and their role in TE. The
      discussion presented here could prove highly useful for the construction of
      scaffolds with requisite features.

PMID- 30291930
TI  - Study of the mechanical degradation mechanism of guar gum in turbulent flow by
      FTIR.
AB  - Guar gum is used in low concentrations as a drag reducing agent in turbulent
      flows to significantly accelerate flow in oil pipelines, oil well operations and
      aqueous systems. Drag reduction also promotes a decrease in energy demand in
      pumping systems. However, the polymers undergo mechanical degradation and lose
      the ability to promote drag reduction over time. In this paper, the drag
      reduction, the power required by the pumps and the degradation of the guar gum
      were evaluated during a turbulent flow of an aqueous solution containing the
      biopolymer. The results indicate the mechanism of degradation of guar gum by the
      hydrolysis of the bond alpha (1 -> 6), liberating the galactose, which justice to
      the loss of efficiency throughout the process. An understanding of this mechanism
      should allow for the development of more mechanically resistant polymers and the
      increase of drag reduction capacity over time.

PMID- 30291931
TI  - A review on injectable chitosan/beta glycerophosphate hydrogels for bone tissue
      regeneration.
AB  - Tissue engineering (TE) is a promising approach for repairing diseased and
      damaged bone tissue. Injectable hydrogel based strategies offer a wide range of
      applications in rapid recovery of bone defects by acting as filler materials and
      depots for delivering various bioactive molecules and averting the need for
      surgical intervention. Chitosan (CS), a natural polysaccharide, forms a
      thermosensitive injectable hydrogel through the addition of beta-glycerophosphate
      (beta-GP). This hybrid hydrogel possesses numerous advantages namely mimicking
      native extracellular matrix (ECM) and providing an amenable microenvironment for
      cell growth. In this review, a brief insight into the gelation mechanism of CS/GP
      hydrogels, modifications, bioactive additives and their applications in treating
      bone defects are presented.

PMID- 30291932
TI  - Fabrication of highly porous N/S doped carbon embedded with ZnS as highly
      efficient photocatalyst for degradation of bisphenol.
AB  - In the present study, a novel nanocomposite has been successfully fabricated that
      contain nitrogen and sulphur doped porous carbon and ZnS nanoparticles. The
      fabricated nanocomposite has been used as a photocatalyst for the photocatalytic
      degradation of bisphenol-A (BPA) under visible light. The prepared nanocomposite
      was characterized using FT-IR, XRD, Raman, SEM, TEM, SAED, BET and XPS. The
      results revealed that the fabricated nanocomposite (ZnS/NSDC) exhibited highly
      porosity due to large surface area 642.24 cm2/g and promising pore volumes.
      ZnS/NSDC nanocomposite was showed excellent photocatalytic performance for BPA
      degradation. During the photocatalytic degradation of BPA, several intermediate
      products with the molecular mass including m/z 151, m/z 133, and m/z 137 were
      observed using LC-MS analyses. The experimental outcomes are supported by
      theoretical calculations via, density functional theory (DFT) and elucidate the
      photocatalytic degradation mechanism of BPA. These efforts suggest that the
      fabricated ZnS/NSDC nanocomposite exhibits excellent properties to severe threat
      to environment and can be used as a reusable photocatalyst for the degradation of
      BPA in aqueous solution.

PMID- 30291933
TI  - Sulfated modification, characterization, antioxidant and hypoglycemic activities
      of polysaccharides from Sargassum pallidum.
AB  - The aim of this study was to investigate the effect of sulfated modification on
      the in vitro antioxidant and hypoglycemic activities of Sargassum pallidum
      polysaccharides (SPP). Three sulfated derivatives (S-SPP1-4, S-SPP1-6 and S-SPP1
      8) were prepared using chlorosulfonic acid-pyridine method under different
      reaction conditions. Physicochemical characterization indicated that sulfated
      modification had successfully occurred. The degrees of substitution (DS) of S
      SPP1-4, S-SPP1-6 and S-SPP1-8 were determined to be ranging from 0.85 to 1.19.
      Sulfated modification resulted in some changes in chemical component, molecular
      weight and monosaccharide composition of SPP. Among these sulfated
      polysaccharides, S-SPP1-4 exhibited the best DPPH and ABTS radical scavenging
      activities, while S-SPP1-8 exhibited the best alpha-glucosidase inhibitory
      activity and promoting-effect on glucose consumption in insulin resistant (IR)
      HepG2 cells. Furthermore, all the sulfated derivatives exhibited better
      hypoglycemic ability than native SPP. These results suggest that appropriately
      sulfated modification could enhance the antioxidant and hypoglycemic activities
      of S. pallidum polysaccharides, which might be used as an alternative derivative
      of natural antioxidant and hypoglycemic agent.

PMID- 30291934
TI  - Production of levan by Bacillus licheniformis NS032 in sugar beet molasses-based
      medium.
AB  - The production of levan by Bacillus licheniformis NS032 in a medium based on
      sugar beet molasses was studied. High polysaccharide yields were produced by
      using diluted molasses (100-140 g/L of total sugars) with the addition of
      commercial sucrose up to 200 g/L of total sugars, as well as K2HPO4. A levan
      yield of 53.2 g/L was obtained on a medium optimized by response surface
      methodology, containing 62.6% of sugar originating from molasses, and 4.66 g/L of
      phosphate, with initial pH value of 7.2. In comparison to the media with 200 and
      400 g/L sucrose, in the molasses optimized medium, the observed bacterial growth
      was faster, while the maximum production of polysaccharide was achieved over a
      shorter time interval (48 h). The polysaccharide produced in molasses medium had
      a weight average molecular weight of 5.82 * 106 Da, degree of branching 12.68%,
      viscosity of 0.24 dL/g, and based on methylation analysis and NMR data, it did
      not significantly differ from levan obtained in the medium with 200 g/L sucrose.

PMID- 30291935
TI  - Elongate mineral particles in the natural environment.
AB  - When considering elongate mineral particles (EMPs) in the natural environment it
      is important to first: 1) define what an elongate mineral is and 2) present what
      we as mineralogists and geologists know about their distribution. However, it is
      often very difficult to define the natural world, instead we physical scientists
      resort to describing it. For instance, we used 1,419 words spread over two pages
      of our mineralogy textbook (Dyar and Gunter, 2008) to describe a mineral. On the
      other hand, elongate has a rather simple non-quantitative definition as a
      particle longer than it is wide; however, to quantify it, we must select an
      aspect ratio. Cleary the term EMP was coined with the hopes to simplify some of
      the confusion resulting in the differing "meanings" of such words as asbestos,
      asbestiform, acicular, and most importantly "fiber" in the natural vs. built
      environment, especially when applied to amphiboles (Gunter, 2010), and non
      regulated asbestiform amphibole species. This paper draws on three sources: 1)
      the USDA-NRCS soil database (Thompson et al., 2011), 2) soil mineralogical data
      from USGS (Smith et al., 2013), and 3) the mineral database created in
      conjunction with the Dyar and Gunter (2008) textbook in an attempt to show issues
      created by use of the term EMP.

PMID- 30291936
TI  - The organophosphate pesticide methamidophos opens the blood-testis barrier and
      covalently binds to ZO-2 in mice.
AB  - Methamidophos (MET) is an organophosphate (OP) pesticide widely used in
      agriculture in developing countries. MET causes adverse effects in male
      reproductive function in humans and experimental animals, but the underlying
      mechanisms remain largely unknown. We explored the effect of MET on mice testes
      (5 mg/kg/day/4 days), finding that this pesticide opens the blood-testis barrier
      and perturbs spermatogenesis, generating the appearance of immature germ cells in
      the epididymis. In the seminiferous tubules, MET treatment changed the level of
      expression or modified the stage-specific localization of tight junction (TJ)
      proteins ZO-1, ZO-2, occludin, and claudin-3. In contrast, claudin-11 was barely
      altered. MET also modified the shape of claudin-11, and ZO-2 at the cell border,
      from a zigzag to a more linear pattern. In addition, MET diminished the
      expression of ZO-2 in spermatids present in seminiferous tubules, induced the
      phosphorylation of ZO-2 and occludin in testes and reduced the interaction
      between these proteins assessed by co-immunoprecipitation. MET formed covalent
      bonds with ZO-2 in serine, tyrosine and lysine residues. The covalent
      modifications formed on ZO-2 at putative phosphorylation sites might interfere
      with ZO-2 interaction with regulatory molecules and other TJ proteins. MET bonds
      formed at ZO-2 ubiquitination sites likely interfere with ZO-2 degradation and TJ
      sealing, based on results obtained in cultured epithelial cells transfected with
      ZO-2 mutated at a MET target lysine residue. Our results shed light on MET male
      reproductive toxicity and are important to improve regulations regarding the use
      of OP pesticides and to protect the health of agricultural workers.

PMID- 30291937
TI  - Andrographolide simultaneously augments Nrf2 antioxidant defense and facilitates
      autophagic flux blockade in cigarette smoke-exposed human bronchial epithelial
      cells.
AB  - Cigarette smoking is the leading cause of chronic obstructive pulmonary disease
      (COPD). Cigarette smoke heightens oxidative stress and impairs autophagy,
      advancing COPD progression. Andrographolide is a bioactive diterpenoid lactone
      isolated from the plant Andrographis paniculata which has been a traditional
      medicinal herb for respiratory diseases. As airway epithelial cells form the
      first interface to be exposed to cigarette smoke, this study aimed to explore the
      modulatory effects of andrographolide on oxidative stress and autophagy in human
      bronchial epithelial BEAS-2B cells exposed to cigarette smoke extract (CSE). CSE
      (2%) exposure increased autophagic markers p62 and LC3B-II levels in BEAS-2B
      cells. Andrographolide alone increased p62 and p-p62 (S349) but not LC3B-II in
      BEAS-2B cells. However, in the presence of CSE, andrographolide was able to
      simultaneously increase LC3B-II level and enhance antioxidant defense by
      decreasing oxidative stress and increasing total antioxidant capacity, through
      upregulation of nuclear Nrf2 via the p62-Nrf2 positive feedback loop. Using RFP
      GFP-LC3B transfected BEAS-2B cells exposed to CSE, andrographolide was found to
      impair autophagosome fusion with lysosome, which may account for the moderate
      increase in activated caspase 3/7 and annexin V levels. Our findings revealed for
      the first time that andrographolide simultaneously upregulated antioxidant
      defense through the p62-Nrf2 loop and moderately induced apoptosis through
      impairment of autophagic flux in CSE-exposed bronchial epithelium.
      Andrographolide facilitated cigarette smoke-induced apoptosis may be a potential
      toxicological outcome or may protect against chronic inflammation and aberrant
      DNA repair. Validation of these in-vitro findings in an experimental COPD model
      by andrographolide is warranted.

PMID- 30291938
TI  - Mechanisms underlying the rapid-acting antidepressant-like effects of
      neuropeptide VGF (non-acronymic) C-terminal peptide TLQP-62.
AB  - Previous studies have revealed that neuropeptide VGF (non-acronymic) C-terminal
      peptide TLQP-62 rapidly activates brain-derived neurotrophic factor
      (BDNF)/tropomyosin receptor kinase B (TrkB)/alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor/mammalian target of rapamycin (mTOR)
      signaling and produces antidepressant-like actions in rodents. In addition, acute
      TLQP-62 infusion also markedly changes the AMPA receptor GluA1 subunit
      phosphorylation at Ser 845 (pGluA1 Ser845) in the PFC of mice, indicating that
      the GluA1 may contributes to the rapid antidepressant-like effects of TLQP-62.
      However, how to regulate the TrkB-mediated signaling and GluA1 changes in the
      prefrontal cortex (PFC) by TLQP-62 remains unclear. Herein, acute administration
      of TLQP-62 into PFC produced rapid-acting antidepressant-like effects in mice.
      Additionally, we confirmed that TLQP-62 ameliorated the depression-like behaviors
      induced by chronic social defeat stress (CSDS) in mice. Further investigation
      demonstrated that this effect of TLQP-62 was mediated by activation of TrkB and
      mTOR, which proceeded to decrease bicaudal C homolog 1 gene (BICC1) and increase
      synaptic protein expression, including GluA1 subunit and pGluA1 Ser845. Notably,
      we further found that beneficial effects of TLQP-62 on depression-like behaviors
      and TrkB/mTOR/BICC1 signaling, GluA1 phosphorylation and GluA1 activation in the
      PFC of mice were significantly abolished by TrkB antagonist ANA-12. In
      conclusion, our findings indicate that TrkB/mTOR/BICC1 signaling, GluA1
      phosphorylation and GluA1 activation in the PFC may involve in the rapid-acting
      antidepressant-like actions of TLQP-62 in mice.

PMID- 30291939
TI  - Dexpramipexole enhances hippocampal synaptic plasticity and memory in the rat.
AB  - Even though pharmacological approaches able to counteract age-dependent cognitive
      impairment have been highly investigated, drugs improving cognition and memory
      are still an unmet need. It has been hypothesized that sustaining energy dynamics
      within the aged hippocampus can boost memory storage by sustaining synaptic
      functioning and long term potentiation (LTP). Dexpramipexole (DEX) is the first
      in-class compound able to sustain neuronal bioenergetics by interacting with
      mitochondrial F1Fo-ATP synthase. In the present study, for the first time we
      evaluated the effects of DEX on synaptic fatigue, LTP induction, learning and
      memory retention. We report that DEX improved LTP maintenance in CA1 neurons of
      acute hippocampal slices from aged but not young rats. However, we found no
      evidence that DEX counteracted two classic parameters of synaptic fatigue such as
      fEPSP reduction or the train area during the high frequency stimulation adopted
      to induce LTP. Interestingly, patch-clamp recordings in rat hippocampal neurons
      revealed that DEX dose-dependently inhibited (IC50 814 nM) the IA current, a
      rapidly-inactivating K+ current that negatively regulates neuronal excitability
      as well as cognition and memory processes. In keeping with this, DEX counteracted
      both scopolamine-induced spatial memory loss in rats challenged in Morris Water
      Maze test and memory retention in rats undergoing Novel Object Recognition.
      Overall, the present study discloses the ability of DEX to boost hippocampal
      synaptic plasticity, learning and memory. In light of the good safety profile of
      DEX in humans, our findings may have a realistic translational potential to
      treatment of cognitive disorders.

PMID- 30291941
TI  - ASIC1a promotes high glucose and PDGF-induced hepatic stellate cell activation by
      inducing autophagy through CaMKKbeta/ERK signaling pathway.
AB  - It is well known that the diabetes mellitus complicates liver fibrosis with high
      morbidity, and Acid-sensing ion Channel 1a (ASIC1a) plays an important role in
      the development of diabetes and liver fibrosis. However, the underlying mechanism
      about how diabetes influences the progression of liver fibrosis remains unclear.
      This study was to investigate the relationship between autophagy and ASIC1a in
      the process of liver fibrosis under hyperglycemia. Interestingly, our study
      showed that the autophagy was elevated in the livers from diabetes combined with
      liver fibrosis double model in vivo and also in rat hepatic stellate cell line
      HSC-T6 after stimulation with high glucose and platelet-derived growth factor
      (PDGF) in vitro, and this response could be attenuated by treatment with ASIC1a
      nonspecific inhibitor Amiloride or specific ShRNA for ASIC1a. Furthermore,
      inhibition of autophagy treated with 3-MA significantly attenuated HSC-T6
      activation and proliferation. Mechanistically, CaMKKbeta/ERK pathway was
      activated in HSC-T6 after stimulation with high glucose and PDGF, and could be
      suppressed by Amiloride. Collectively, we concluded that autophagy induced by
      ASIC1a contributes to HSC-T6 activation, which ing pathway.

PMID- 30291940
TI  - Effects of acute Delta9-tetrahydrocannabinol on next-day extinction recall is
      mediated by post-extinction resting-state brain dynamics.
AB  - We have previously demonstrated that an acute dose of Delta9
      tetrahydrocanninbinol (THC), administered prior to extinction learning,
      facilitates later recall of extinction learning and modulates the underlying
      neural circuitry, including the ventromedial prefrontal cortex (vmPFC),
      hippocampus (HPC), and amygdala (AMYG). It remains unknown whether THC-induced
      changes in fear-extinction neural circuitry can be detected following extinction
      learning, which may reflect ongoing processes involved consolidation of the
      extinction memory. To address this gap, we used a randomized, double-blind,
      placebo-controlled, between-subjects design to compare acute pharmacological
      effects of THC (7.5 mg) vs. placebo (PBO) on post-extinction resting-state
      functional connectivity (RS-FC) within fear-extinction circuitry in 77 healthy
      adults (THC = 40; PBO = 37). RS-FC was examined between vmPFC, HPC, and AMYG
      using two complementary approaches: 1) static RS-FC (average correlation in ROI
      ROI pairs across the entire scan); and 2) dynamic (i.e., time-varying) RS-FC
      (sliding window correlation time series' variance). RS-FC was then linked to
      behavioral and brain measures of extinction recall. Compared to PBO, THC
      administration was associated with lower AMYG-HPC static RS-FC, but higher AMYG
      vmPFC dynamic RS-FC. Lower AMYG-HPC static RS-FC was associated with higher HPC
      activation, as well as, better extinction recall. Moreover, lower AMYG-HPC static
      RS-FC following extinction learning mediated the link between THC administration
      and extinction recall. Post-extinction RS-FC patterns may reflect sustained
      effects of THC on fear-extinction circuitry even in the absence of an overt task,
      and/or effects of ongoing processes that serve to strengthen the neural
      connections supporting the consolidation of the memory and better extinction
      recall.

PMID- 30291942
TI  - In response to, "Systematic review and health risk assessment of arsenic and lead
      in the fished shrimps from the Persian Gulf," by Fakhri et al.

PMID- 30291943
TI  - Phytochemical analysis and anti-inflammatory effects of Filipendula vulgaris
      Moench extracts.
AB  - Filipendula vulgaris Moench (dropwort) is used in traditional medicine for
      relieving various inflammation-related diseases. In the present study, the
      phytochemical profile of F. vulgaris aerial part (FVA) and root (FVR) methanolic
      extracts was evaluated by LC-DAD-HRMS analysis. Furthermore, their in vitro and
      in vivo anti-inflammatory effects, as well as their potential cytotoxicity, were
      assessed. Results showed that the extracts mainly contain phenolics like
      flavonoids, hydrolyzable tannins, procyanidins, and phenolic acid derivatives,
      including gaultherin. No in vitro cytotoxicity was found at the highest
      concentration (50 MUg/mL). FVA extract (50 MUg/mL) significantly inhibited
      cyclooxygenase-1 and -2 (COX-1 and COX-2) activities in vitro (>50% inhibition),
      and FVR extract considerably inhibited COX-2 activity (52.5 +/- 2.7%) without
      affecting COX-2 gene expression in LPS-stimulated THP-1 cells. The extracts
      demonstrated prominent in vivo anti-inflammatory potential upon oral
      administration in rats. Especially FVA extract at 100 and 200 mg/kg significantly
      inhibited carrageenan-induced edema formation. From these results, it can be
      concluded that F. vulgaris extracts possess interesting anti-inflammatory
      properties.

PMID- 30291944
TI  - Coffee, caffeine, chlorogenic acid, and the purinergic system.
AB  - Coffee is a drink prepared from roasted coffee beans and is lauded for its aroma
      and flavour. It is the third most popular beverage in the world. This beverage is
      known by its stimulant effect associated with the presence of methylxanthines.
      Caffeine, a purine-like molecule (1,3,7 trymetylxantine), is the most important
      bioactive compound in coffee, among others such as chlorogenic acid (CGA),
      diterpenes, and trigonelline. CGA is a phenolic acid with biological properties
      as antioxidant, anti-inflammatory, neuroprotector, hypolipidemic, and
      hypoglicemic. Purinergic system plays a key role inneuromodulation and
      homeostasis. Extracellular ATP, other nucleotides and adenosine are signalling
      molecules that act through their specific receptors, namely purinoceptors, P1 for
      nucleosides and P2 for nucleotides. They regulate many pathological processes,
      since adenosine, for instance, can limit the damage caused by ATP in the
      excitotoxicity from the neuronal cells. The primary purpose of this review is to
      discuss the effects of coffee, caffeine, and CGA on the purinergic system. This
      review focuses on the relationship/interplay between coffee, caffeine, CGA, and
      adenosine, and their effects on ectonucleotidases activities as well as on the
      modulation of P1 and P2 receptors from central nervous system and also in
      peripheral tissue.

PMID- 30291945
TI  - Renal toxicity through AhR, PXR, and Nrf2 signaling pathway activation of
      ochratoxin A-induced oxidative stress in kidney cells.
AB  - Because ochratoxin A (OTA) is widely found in foods, people are susceptible to
      OTA exposure. The mechanism leading to renal toxicity induced by OTA remains
      unclear. The aim of this study was to investigate OTA-induced toxicity in human
      proximal tubule HK-2 cells. OTA decreased cell viability, and the expression of
      kidney injury molecule-1 (KIM-1), a kidney damage marker, was increased when HK-2
      cells were exposed to OTA. Additionally, OTA treatment of cells increased
      intracellular reactive oxygen species and malondialdehyde and decreased
      glutathione levels. OTA-treated cells induced the aryl hydrocarbon receptor (AhR)
      and pregnane X receptor (PXR) genes followed by induction of the cytochrome P450
      1A1 (CYP1A1), CYP1A2, and CYP3A4 genes representing phase I enzyme. The mRNA
      expression of phase II enzymes such as heme oxygenase-1, nicotinamide adenine
      dinucleotide phosphate-quinone oxidoreductase 1, and glutamate cysteine ligase
      catalytic subunit were upregulated by activation of NF-E2-related factor 2 (Nrf2)
      translocation by treatment with OTA. The response of OTA-orally administered mice
      also showed marked increases in these enzymes as well as KIM-1. These results
      indicate that OTA induces phase I and II enzymes through the AhR, PXR, and Nrf2
      signaling pathways in HK-2 cells, which may lead to modulation of proximal tubule
      injury.

PMID- 30291946
TI  - Targeting thioredoxin glutathione reductase as a potential antischistosomal drug
      target.
AB  - Schistosomiasis represents a world health major problem affecting more than 206
      million people worldwide. Up to date, praziquantel (PZQ) is the sole
      chemotherapeutic agent used in clinics for the treatment of schistosomiasis. The
      resistance to PZQ chemotherapy that has been emerged against some schistosome
      phenotypes represents the most serious PZQ-related problem so far. Therefore, it
      is clear that there is a substantial need to develop novel and effective
      antischistosomal agents in order to ensure the effective drug control of
      schistosomiasis in the future. It is well-documented that the thiol redox
      homeostasis of schistosomes is entirely based on a single enzyme named
      thioredoxin-glutathione reductase (TGR). Thus, TGR is an essential protein for
      the survival of schistosomes which means that TGR is a valid and promising target
      for the recent antischistosomal drug-discovery approaches. This review aimed to
      shed light on potential lead compounds that may inhibit TGR activity and
      consequently could be tested as a potential antischistsomal drugs. In the current
      review we discussed multiple drug discovery approaches for new compounds
      targeting TGR and its implementation.

PMID- 30291947
TI  - Loss of cAMP-dependent stimulation of isolated cilia motility by alcohol exposure
      is oxidant dependent.
AB  - Alcohol exposure is associated with decreased mucociliary clearance, a key innate
      defense essential to lung immunity. Previously we identified that prolonged
      alcohol exposure results in dysfunction of airway cilia that persists at the
      organelle level. This dysfunction is characterized by a loss of 3',5'-cyclic
      adenosine monophosphate (cAMP)-mediated cilia stimulation. However, whether or
      not ciliary dysfunction develops intrinsically at the organelle level has not
      been explored. We hypothesized that prolonged alcohol exposure directly to
      isolated demembranated cilia (axonemes) causes ciliary dysfunction. To test this
      hypothesis, we exposed isolated axonemes to alcohol (100 mM) for 1-24 h and
      assessed ciliary beat frequency (CBF) in response to cAMP at 1, 3, 4, 6 and 24 h
      post exposure. We found that after 1 h of alcohol exposure cilia axonemes do not
      increase CBF in response to cAMP. Importantly, by 6 h after the initial exposure
      to alcohol, cAMP-mediated CBF was restored to control levels. Additionally, we
      found that thioredoxin reverses ciliary dysfunction in axonemes exposed to
      alcohol. Finally, we identified, using a combination of a xanthine oxidase
      oxidant-generating system, direct application of hydrogen peroxide, and electron
      paramagnetic resonance, that hydrogen peroxide versus superoxide, is likely the
      key oxidant species driving alcohol-induced ciliary dysfunction in isolated
      axonemes. These data highlight the role of alcohol to stimulate local production
      of oxidants in the axoneme to cause ciliary dysfunction. Additionally, these data
      specifically add hydrogen peroxide as a potential therapeutic target in the
      treatment or prevention of alcohol-associated ciliary dysfunction and subsequent
      pneumonia.

PMID- 30291948
TI  - An association between MMP-9 and impaired T cell migration in ethanol-fed BALB/c
      mice infected with Respiratory Syncytial Virus-2A.
AB  - Matrix metalloproteinases are important for proper airway matrix structure and
      wound healing. These enzymes are also implicated in many airway diseases.
      Previously, chronic ethanol consumption was shown to prolong inflammation and
      delay viral clearance in respiratory syncytial virus (RSV)-infected mice. We
      hypothesize that alcohol alters anti-viral immunity by disrupting immune cell
      chemotaxis in the lung. BALB/c mice were randomly selected to consume 18% alcohol
      ad libitum for 8 weeks prior to infection with RSV-2A. Bronchoalveolar lavage
      (BAL) cell populations were measured by flow cytometry and chemokines detected by
      Western blot or ELISA. MMP-9 levels were determined by polymerase chain reaction
      (PCR) in mouse lungs and in BAL fluid by ELISA. T cells were acquired from the
      spleens of water-fed, non-infected control mice (CTRL); alcohol-fed, non-infected
      (ETOH); water-fed, RSV-infected (RSV); or ethanol-fed, RSV-infected (ETOH-RSV) 4
      days after RSV infection. T cells were placed in a transmigration system where
      chemokines had been treated with and without activated MMP-9. Lymphocyte
      recruitment was significantly reduced in the BAL 4 days after RSV infection in
      ETOH-RSV mice, whereas chemokine levels were the highest in this group at all
      experimental time points examined in comparison to RSV (P< 0.05). MMP-9 mRNA and
      protein were detected at high levels in ETOH-RSV mice compared to RSV. Using ex
      vivo transmigration to CCL2 and CXCL10, T cell migration was not impaired between
      any of the treatment groups, yet when CCL2 and CXCL10 were treated with activated
      MMP-9, significantly fewer T cells migrated across collagen-coated 5MUm membranes
      (P < 0.05). Immune cell recruitment is necessary for viral clearance. We show
      that immune cells are decreased in the lungs of ETOH-RSV mice. In contrast to
      decreased cell recruitment, key inflammatory chemokines were elevated in the
      lungs of ETOH-RSV mice. These proteins may be prematurely degraded by MMP-9 in
      the lung, leading to defective immunity and reduced viral clearance.

PMID- 30291949
TI  - Control and Context Are Central for People With Advanced Illness Experiencing
      Breathlessness: A Systematic Review and Thematic Synthesis.
AB  - CONTEXT: Breathlessness is common and distressing in advanced illness. It is a
      challenge to assess, with few effective treatment options. To evaluate new
      treatments, appropriate outcome measures that reflect the concerns of people
      experiencing breathlessness are needed. OBJECTIVES: The objective of this study
      was to systematically review and synthesize the main concerns of people with
      advanced illness experiencing breathlessness to guide comprehensive clinical
      assessment and inform future outcome measurement in clinical practice and
      research. METHODS: This is a systematic review following Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses methodology. MEDLINE (1946-2017),
      PsycINFO (1806-2017), and EMBASE (1974-2017), as well as key journals, gray
      literature, reference lists, and citation searches, identified qualitative
      studies exploring the concerns of people living with breathlessness. Included
      studies were quality-assessed using the Critical Appraisal Skills Program
      checklist and analyzed using thematic synthesis. RESULTS: We included 38 studies
      with 672 participants. Concerns were identified across six domains of "total"
      breathlessness: physical, emotional, spiritual, social, control, and context
      (chronic and episodic breathlessness). Four of these have been previously
      identified in the concept of "total dyspnea." Control and context have been newly
      identified as important, particularly in their influence on coping and help
      seeking behavior. The importance of social participation, impact on
      relationships, and loss of perceived role within social and spiritual domains
      also emerged as being significant to individuals. CONCLUSION: People with
      advanced illness living with breathlessness have concerns in multiple domains,
      supporting a concept of "total breathlessness." This adapted model can help to
      guide comprehensive clinical assessment and inform future outcome measurement in
      clinical practice and research.

PMID- 30291950
TI  - Preferences for Help With a Sleep Problem Before Starting Cancer Treatment.

PMID- 30291951
TI  - Introduction of bifunctional alcohol/acetaldehyde dehydrogenase gene (adhE) in
      Fructobacillus fructosus settled its fructophilic characteristics.
AB  - Fructophilic lactic acid bacteria (FLAB) are unique in the sense that they prefer
      D-fructose over D-glucose as main carbon source. If D-glucose is metabolised,
      electron acceptors are required and significant levels of acetate are produced.
      These bacteria are found in environments rich in D-fructose, such as flowers,
      fruits and the gastrointestinal tract of insects feeding on fructose-rich diets.
      Fructobacillus spp. are representatives of this unique group, and their
      fructophilic characteristics are well conserved. In this study, the bifunctional
      alcohol/acetaldehyde dehydrogenase gene (adhE) from Leuconostoc mesenteroides
      NRIC 1541T was cloned into a plasmid and transferred to Fructobacillus fructosus
      NRIC 1058T. Differences in biochemical characteristics between the parental
      strain (NRIC 1058T) and the transformants were compared. Strain 1-11, transformed
      with the adhE gene, did not show any fructophilic characteristics, and the strain
      grew well on D-glucose without external electron acceptors. Accumulation of
      acetic acid, which was originally seen in the parental strain, was replaced with
      ethanol in the transformed strain. Furthermore, in silico analyses revealed that
      strain NRIC 1058T lacked the sugar transporters/permeases and enzymes required
      for conversion of metabolic intermediates. This may be the reason for poor
      carbohydrate metabolic properties recorded for FLAB.

PMID- 30291952
TI  - Long-term efficacy of combination vismodegib and photodynamic therapy for
      multiple basal cell carcinomas.

PMID- 30291955
TI  - Behavioral response to imipramine under chronic mild stress corresponds with
      increase of mRNA encoding somatostatin receptors sst2 and sst4 expression in
      medial habenular nucleus.

PMID- 30291954
TI  - The effect of age, sex and strains on the performance and outcome in animal
      models of stroke.
AB  - Stroke is one of the leading causes of death worldwide, and the majority of
      cerebral stroke is caused by occlusion of cerebral circulation, which eventually
      leads to brain infarction. Although stroke occurs mainly in the aged population,
      most animal models for experimental stroke in vivo almost universally rely on
      young-adult rodents for the evaluation of neuropathological, neurological, or
      behavioral outcomes after stroke due to their greater availability, lower cost,
      and fewer health problems. However, it is well established that aged animals
      differ from young animals in terms of physiology, neurochemistry, and behavior.
      Stroke-induced changes are more pronounced with advancing age. Therefore, the
      overlooked role of age in animal models of stroke could have an impact on data
      quality and hinder the translation of rodent models to humans. In addition to
      aging, other factors also influence functional performance after ischemic stroke.
      In this article, we summarize the differences between young and aged animals, the
      impact of age, sex and animal strains on performance and outcome in animal models
      of stroke and emphasize age as a key factor in preclinical stroke studies.

PMID- 30291953
TI  - Tyrosol attenuates pro-inflammatory cytokines from cultured astrocytes and NF
      kappaB activation in in vitro oxygen glucose deprivation.
AB  - Subsequent inflammation in stroke plays an important role in the damage of
      neurons in the perilesional area. Therapeutic intervention targeting inflammation
      may be a promising complementary strategy to current treatments of stroke. Here,
      we explored the possible beneficial effects of tyrosol, a derivative of phenethyl
      alcohol and natural antioxidant, playing an anti-inflammatory role in astrocyte
      culture and in vitro oxygen glucose deprivation (OGD) model. MTT, western blot,
      ELISA and EMSA assays were carried out to investigate cell viability, protein
      expression level, cytokine expression and NF-kappaB activity. We found tyrosol
      protected cultured astrocytes against OGD-induced cell viability loss in MTT
      test. Meanwhile, tyrosol attenuated the released TNF-alpha and IL-6 level from
      astrocyte via regulating Janus N-terminal kinase (JNK). The reduction of
      cytokines from astrocyte might be due to its inhibition of astrocyte activation
      and regulation of STAT3 signaling pathway since tyrosol attenuated the expression
      level of GFAP (glial fibrillary acidic protein) and the phosphorylation of STAT3.
      Additionally, we demonstrated that tyrosol prevented the degradation of
      IkappaBalpha and the increase of IkappaBalpha phosphorylation in astrocytes
      exposed to OGD, which led to the suppression of NF-kappaB function during
      ischemia. Collectively, our results showed that tyrosol may be a promising
      complementary treatment compound for stroke via modulating the inflammatory
      response in astrocytes during ischemia.

PMID- 30291956
TI  - Uncaria rhynchophylla ameliorates amyloid beta deposition and amyloid beta
      mediated pathology in 5XFAD mice.
AB  - One of the pathological hallmarks of Alzheimer's disease (AD) is the abnormal
      aggregation of amyloid beta (Abeta) peptides. Uncaria rhynchophylla (UR), one of
      the Uncaria species, has long been used to treat neurodegenerative disease. In
      particular, it has been reported that UR inhibits aggregation of Abeta in vitro.
      However, little is known about the histological effects of UR treatment on Abeta
      pathology in AD animal models. In the present study, we investigated the effect
      of UR on Abeta aggregation, Abeta-mediated pathologies and adult hippocampal
      neurogenesis in the brain of 5XFAD mice. First, using the thioflavin T assay and
      amyloid staining, we demonstrated that UR treatment effectively inhibited Abeta
      aggregation and accumulation in the cortex and subiculum. Second,
      immunofluorescence staining showed that administration of UR attenuated gliosis
      and neurodegeneration in the subiculum and cortex. Third, UR treatment
      ameliorated impaired adult hippocampal neurogenesis. The present results indicate
      that UR significantly alleviates Abeta deposition and Abeta-mediated
      neuropathology in the brain in 5XFAD mice, suggesting the potency of UR as a
      preventive and therapeutic agent for AD.

PMID- 30291957
TI  - A Poloxamer-407 modified liposome encapsulating epigallocatechin-3-gallate in the
      presence of magnesium: Characterization and protective effect against oxidative
      damage.
AB  - Epigallocatechin-3-gallate (EGCG) is a polyphenolic catechin from green tea, well
      known for being bioactive in age-associated pathologies where oxidative stress
      plays a preeminent role. The activity of this molecule is however contrasted by
      its high chemical and metabolic instability that determines a poor concentration
      of the antioxidant within the biological system after administration. In order to
      protect the molecule and increase its delivery efficiency, we have encapsulated
      EGCG inside anionic liposomes made of 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine and cholesteryl
      hemisuccinate. To maximize EGCG internalization, magnesium salt was added in the
      preparation. However stable nanodispersions suitable for drug delivery were
      obtained only after treatment with Poloxamer-407, a polyethylene-propylene glycol
      copolymer. The structural and morphological properties of the produced dispersion
      were studied by X-ray diffraction, which showed a multilamellar structure even
      after EGCG addition and an ordering effect of Poloxamer-407; Dynamic Light
      Scattering demonstrated serum stability of the liposomes. The characterization
      was completed by evaluating both encapsulation efficiency (100%, in the final
      formulation) and in vitro EGCG release. Since oxidative stress is involved in
      numerous retinal degenerative diseases, such as age-related macular degeneration,
      the ability of these liposomes to contrast H2O2-induced cell death was assessed
      in human retinal cells. Morphological changes at the subcellular level were
      analyzed by Transmission Electron Microscopy, which showed that mitochondria were
      better preserved in cells treated with liposomes then those treated with free
      EGCG. In conclusion, the results demonstrated that the produced formulation
      enhances the efficacy of EGCG under stress conditions, thus representing a
      potential formulation for the intracellular delivery of EGCG in diseases caused
      by oxidative damage.

PMID- 30291958
TI  - Prevention of rat liver fibrosis by selective targeting of hepatic stellate cells
      using hesperidin carriers.
AB  - Therapeutic efficacy of antifibrotic drugs can be improved by targeting hepatic
      stellate cells (HSCs). This study investigated the prospect of developing a
      carrier system for the effective delivery of hesperidin by selectively targeting
      HSCs in fibrotic rat model. Hesperidin-loaded surface modified liposome
      formulations were prepared with varying quantity of lipids to optimize
      physicochemical characteristics. Best liposome formulation was further conjugated
      with a homing ligand, recognized by HSCs, to achieve a carrier system that
      facilitates the targeting of hesperidin. This carrier system was characterized
      for various physicochemical properties. The effectiveness of the bioactive
      carrier to prevent liver fibrosis was investigated by carrying out biochemical,
      biodistribution, and histopathological analyses. The pharmaceutical properties
      demonstrated by the ligand conjugated carrier system were optimal to facilitate
      selective and preferential delivery to the liver. Steady and prolonged drug
      release behavior with zero order kinetics displayed by prepared carrier system
      established its prospect to increase efficiency and decrease dosing of
      hesperidin. The pharmacokinetic profile of the carrier system was very distinct
      and exhibited rapid plasma clearance. The bio-distribution data of formulated
      carrier system indicates higher uptake of hesperidin predominantly by fibrotic
      liver with insignificant amount in non-targeted organs, which is certainly
      beneficial due to low risk of toxicity and lower systemic distribution. In
      conclusion, this developed carrier represents a potentially beneficial approach
      for HSCs specific targeting of hesperidin in a rat model with liver fibrosis.

PMID- 30291959
TI  - Novel ultra-small micelles based on rebaudioside A: A potential nanoplatform for
      ocular drug delivery.
AB  - We investigated if the self-assembled micelles of rebaudioside A (RA) could
      potentially be utilized as an ocular drug-delivery system in this investigation.
      RA self-assembled into micelles with ultra-small particle sizes (<4 nm) in a
      homogeneous distribution state (polydispersity index < 0.3). RA had good cellular
      tolerance and no cytotoxicity was observed at concentrations <= 18.5 mg/ml at 72
      h of incubation. RA also did not cause cell apoptosis at concentration <= 12
      mg/ml. Coumarin-6 (Cou6)-loaded RA micelles had good cellular tolerance and in
      vivo non-irritants to the rabbit eyes. RA micelles dramatically improved the
      cellular uptake of Cou6 (compared to free-Cou6 P < 0.05); an energy-independent,
      active, intracellular endocytosis pathway was apparently involved, and cellular
      organelles such as lysosomes, endoplasmic reticuli, and mitochondria were
      observed with a high distribution of Cou6, while a much more sophisticated
      endocytosis pathway was apparently involved in the ex vivo corneal endocytosis
      mechanism tests. The use of RA micelles significantly improved in vivo corneal
      permeation of the encapsulated Cou6 when compared to free-Cou6 eye drops (P <
      0.05). These findings indicate that RA micelle formulations have great potential
      as a novel ocular drug-delivery system to improve the bioavailability of
      hydrophobic drugs.

PMID- 30291960
TI  - A novel antibacterial agent based on AgNPs and Fe3O4 loaded chitin microspheres
      with peroxidase-like activity for synergistic antibacterial activity and wound
      healing.
AB  - In this study, a novel antibacterial agent was developed based on chitin
      nanofibrous microspheres loaded with AgNPs and Fe3O4 nanoparticles (Ag-Fe3O4-NMs)
      for synergistic antibacterial activity and wound healing. Ag-Fe3O4-NMs was
      prepared via an in situ synthetic method which showed an excellent porosity and
      wettability. Moreover, Ag-Fe3O4-NMs were capable of sustained release of Ag+ and
      catalysed the decomposition of low H2O2 concentrations to generate hydroxyl
      radical (OH). The OH and Ag+ showed higher antibacterial activity and inhibited
      the toxicity with high dose of AgNPs and H2O2. In vitro biocompatibility results
      suggested that Ag-Fe3O4-NMs have low toxicity and low hemolysis. Thus, a novel
      antibacterial agent with enhanced synergistic antibacterial activity was obtained
      by combination of Ag-Fe3O4-NMs and H2O2 at a low and biologlically safe dosage,
      which could facilitate fibroblast growth, accelerate epithelialization, and
      promote the healing rate of infected wounds.

PMID- 30291961
TI  - Smart pH responsive drug delivery system based on poly(HEMA-co-DMAEMA)
      nanohydrogel.
AB  - The advent of smart nanohydrogel has revealed new opportunities for scientists to
      develop the most efficient anti-cancer vehicles with safe and biocompatible
      profile. In this experiment, using reversible addition-fragmentation chain
      transfer polymerization method as a novel, safe and smart pH responsive
      formulation of poly (hydroxyethyl methacrylate-co-N,N-dimethylaminoethyl
      methacrylate) and poly (ethylene glycol)-diacrylate as cross-linker were
      synthesized. The synthesized structure was confirmed by Fourier-transform
      infrared spectroscopy and proton nuclear magnetic resonance methods. The pH
      responsive behavior of the synthesized particles was checked by size measurement
      in two different pH values (5.5 and 7.4) by dynamic light scattering and
      transmission electron microscopy. The prepared structure had nanometer sizes of
      180 in medium with pH of 7.4, when it encountered acidic medium (e.g. pH 5.5),
      the particles swelled to about 400 nm. The efficiency of the prepared pH
      responsive nanohydrogels was tested as a drug delivery system. An anti-cancer
      drug, doxorubicin successfully interacted with this material. The release
      profiles of nanoparticles carrying drug molecules were checked in two different
      simulated pH of healthy organs (7.4) and tumor site (5.5). Despite lower release
      in pH of 7.4 (~20%), an increased drug release of 80% was obtained in pH of 5.5.
      The in vitro toxicity assay, apoptosis evaluation and uptake experiments were
      performed on breast cancer cell line (MCF-7), which showed a time dependency
      cellular entrance, an enhanced cytotoxicity and apoptosis induction by the
      doxorubicin loaded nanoparticles. Hemolysis assays confirmed the safety and
      hemocompatibility of the developed nanohydrogel. The suitable size (<200 nm), pH
      responsive behavior, anti-proliferative activity and apoptosis induction in
      cancer cells and hemocompatibility were the noticeable features of the developed
      doxorubicin adsorbed nanoparticle, which introduced this formulation as an ideal
      vehicle in anti-cancer drug delivery.

PMID- 30291962
TI  - A 5-lipoxygenase-specific sequence motif impedes enzyme activity and confers
      dependence on a partner protein.
AB  - Leukotrienes (LT) are lipid mediators of the inflammatory response that play key
      roles in diseases such as asthma and atherosclerosis. The precursor leukotriene
      A4 (LTA4) is synthesized from arachidonic acid (AA) by 5-lipoxygenase (5-LOX), a
      membrane-associated enzyme, with the help of 5-lipoxygenase-activating protein
      (FLAP), a nuclear transmembrane protein. In lipoxygenases the main chain
      carboxylate of the C-terminus is a ligand for the non-heme iron and thus part of
      the catalytic center. We investigated the role of a lysine-rich sequence (KKK653
      655) 20 amino acids upstream of the C-terminus unique to 5-LOX that might
      displace the main-chain carboxylate in the iron coordination sphere. A 5-LOX
      mutant in which KKK653-655 is replaced by ENL was transfected into HEK293 cells
      in the absence and presence of FLAP. This mutant gave ~20-fold higher 5-LOX
      product levels in stimulated HEK cells relative to the wild-type 5-LOX. Co
      expression of the enzymes with FLAP led to an equalization of 5-LOX products
      detected, with wild-type 5-LOX product levels increased and those from the mutant
      enzyme decreased. These data suggest that the KKK motif limits 5-LOX activity and
      that this attenuated activity must be compensated by the presence of FLAP as a
      partner protein for effective LT biosynthesis.

PMID- 30291963
TI  - Simplified end-to-end continuous manufacturing by feeding API suspensions in twin
      screw wet granulation.
AB  - This study focussed on investigating the coupling of continuous manufacturing of
      drug substance and continuous manufacture of drug product. An important step in
      such an integrated end-to-end continuous manufacturing was envisioned by dosing
      the API as suspension into a twin-screw wet granulation process. To achieve this
      goal, a model drug substance (ibuprofen) was fed as a concentrated aqueous
      suspension (50% w/w) into a twin-screw granulator and compared against
      traditional solid feeding of the model drug substance to meet a target ibuprofen
      load of 60% w/w in the formulation. Granulation and compaction behaviour were
      evaluated to determine the impact of feeding API as suspension in twin-screw wet
      granulation on the critical quality attributes of the drug product. It was
      demonstrated that the ibuprofen suspension feed is comparable with the ibuprofen
      dry blend feed in twin-screw wet granulation. Next to enabling end-to-end
      continuous manufacturing, API suspension feed in twin-screw wet granulation could
      afford a number of additional advantages including manufacturing efficiency by
      removing the drying step for API, or overcoming processing issues linked to the
      bulk properties of the API powder (e.g. flowability).

PMID- 30291964
TI  - Structural insights into pH-responsive drug release of self-assembling human
      serum albumin-silk fibroin nanocapsules.
AB  - Inflammation processes are associated with significant decreases in tissue or
      lysosomal pH from 7.4 to 4, a fact that argues for the application of pH
      responsive drug delivery systems. However, for their design and optimization a
      full understanding of the release mechanism is crucial. In this study we
      investigated the pH-depending drug release mechanism and the influence of silk
      fibroin (SF) concentration and SF degradation degree of human serum albumin (HSA)
      SF nanocapsules. Sonochemically produced nanocapsules were investigated regarding
      particle size, colloidal stability, protein encapsulation, thermal stability and
      drug loading properties. Particles of the monodisperse phase showed average
      hydrodynamic radii between 438 and 888 nm as measured by DLS and AFM and a zeta
      potential of -11.12 +/- 3.27 mV. Together with DSC results this indicated the
      successful production of stable nanocapsules. ATR-FTIR analysis demonstrated that
      SF had a positive effect on particle formation and stability due to induced beta
      sheet formation and enhanced crosslinking. The pH-responsive release was found to
      depend on the SF concentration. In in-vitro release studies, HSA-SF nanocapsules
      composed of 50% SF showed an increased pH-responsive release for all tested model
      substances (Rhodamine B, Crystal Violet and Evans Blue) and methotrexate at the
      lowered pH of 4.5 to pH 5.4, while HSA capsules without SF did not show any pH
      responsive drug release. Mechanistic studies using confocal laser scanning
      microscopy (CLSM) and small angle X-ray scattering (SAXS) analyses showed that
      increases in particle porosity and decreases in particle densities are directly
      linked to pH-responsive release properties. Therefore, the pH-responsive release
      mechanism was identified as diffusion controlled in a novel and unique approach
      by linking scattering results with in-vitro studies. Finally, cytotoxicity
      studies using the human monocytic THP-1 cell line indicated non-toxic behavior of
      the drug loaded nanocapsules when applied in a concentration of 62.5 ug mL-1.
      Based on the obtained release properties of HSA-SF nanocapsules formulations and
      the results of in-vitro MTT assays, formulations containing 50% SF showed the
      highest requirements arguing for future in vivo experiments and application in
      the treatment of inflammatory diseases.

PMID- 30291965
TI  - Nitric oxide inhibitory coumarins from the roots and rhizomes of Notopterygium
      incisum.
AB  - Phytochemical study on the roots and rhizomes of Notopterygium incisum resulted
      in the isolation of six new coumarins, notoptetherins A - F (1-6), and 20 known
      analogues (7-26). Their structures were elucidated on the basis of extensive
      analyses of NMR and HRMS data, and the absolute configurations of 5 and 6 were
      established by Mo2(AcO)4-induced CD and exciton chirality, respectively.
      Moreover, a biomimetic synthesis of 6 from 21 was employed to confirm its
      absolute configuration. In a subsequent activity screening, compounds 12 and 17
      exhibited potent inhibition against LPS-induced nitric oxide production in RAW
      264.7 cells with IC50 values of 12.7 and 10.2 MUM, respectively.

PMID- 30291966
TI  - A pharmacokinetic study on oleracone C after oral and intravenous administration.
AB  - Oleracone C, a new homoisoflavanone recently isolated from the plant Portulaca
      oleracea L., has obvious pharmacological activities. Subsequently, its
      pharmacokinetic profiles in rats' plasma after oral and intravenous
      administrations were studied by a simple and rapid ultra high-performance liquid
      chromatography electrospray ionization quadrupole-time of flight mass
      spectrometry (UHPLC-ESI-Q-TOF/MS) with apigenin as an internal standard (IS). The
      analysis was performed on an Agilent Zorbax Eclipse Plus C18 Column (2.1 * 50 mm,
      1.8 MUm) by elution with acetonitrile and water (containing 0.1% formic acid) at
      a flow rate of 0.3 mL/min. Electrospray ionization in negative ion mode was used
      to quantify oleracone C and apigenin, with monitored ion m/z values of 299.0915
      [M - H]- and 269.0455 [M - H]-. The linear range was established over the
      concentration range 10-2000 ng/mL (r = 0.9971). The limit of detection (LOD) and
      limit of quantification (LOQ) were 3 and 10 ng/mL for oleracone C, respectively.
      The RSD and RE of intra- and inter- day accuracy and precision were all less than
      15%. The pharmacokinetic results indicated that oleracone C was rapidly
      distributed with the time to peak concentrations of 0.03 h and 0.33 h,
      respectively after intravenous and oral administrations and presented a low
      absolute bioavailability of 8.32%. This is the first study to successfully
      examine the pharmacokinetics of homoisoflavanone in rats' plasma after oral and
      intravenous administrations, using rapid, sensitive and specific UHPLC-ESI-Q
      TOF/MS method.

PMID- 30291967
TI  - New antimicrobial compounds produced by endophytic Penicillium janthinellum
      isolated from Panax notoginseng as potential inhibitors of FtsZ.
AB  - A total of 180 fungal isolates, belonging to 20 genera and 47 species, were
      obtained from the roots, stems and leaves of Panax notoginseng. One isolate, the
      endophytic fungus Penicillium janthinellum SYPF 7899, displayed the strongest
      antibacterial activity and was studied for its production of secondary
      metabolites. In total, three new compounds, including rotational isomers 1a, 1b
      and 2 were isolated from the solid cultures of P. janthinellum, as well as eight
      known compounds (3-10). These structures were determined on the basis of 1D, 2D
      NMR and electronic circular dichroism (ECD) spectroscopic analyses as well as
      theoretical calculations. Compound 1 exhibited significant inhibitory activities
      against Bacillus subtilis and Staphylococcus aureus with MIC values of 15 and 18
      MUg/ml, respectively. The other compounds showed moderate or weak activities. In
      addition, morphological observation showed the rod-shaped cells of B. subtilis
      growing into long filaments, which reached 1.5- to 2-fold of the length of the
      original cells after treatment with compound 1. The coccoid cells of S. aureus
      exhibited a similar response and swelled to a 2-fold volume after treatment with
      compound 1. In silico molecular docking was explored to study the binding
      interactions between the compounds and the active sites of filamentous
      temperature-sensitive protein Z (FtsZ) from B. subtilis and S. aureus. Compound
      1a, 1b and 2 showed high binding energies, strong H-bond interactions and
      hydrophobic interactions with FtsZ. Based on the antimicrobial activities,
      cellular phenotype observation and docking studies, compound 1 is considered to
      be a promising antimicrobial inhibitor of FtsZ.

PMID- 30291968
TI  - Purification and functional characterization of tomato mosaic virus 130K protein
      expressed in silkworm pupae using a baculovirus vector.
AB  - Tomato mosaic virus (ToMV; genus, Tobamovirus) is a member of the alpha-like
      virus superfamily of positive-strand RNA viruses, which includes many plant and
      animal viruses of agronomical and clinical importance. The genomes of alpha-like
      viruses encode replication-associated proteins that contain methyltransferase,
      helicase and/or polymerase domains. The three-dimensional structure of the
      helicase domain fragment of ToMV has been determined, but the structures of the
      other domains of alpha-like virus replication proteins are not available. In this
      study, we expressed full-length ToMV replication-associated protein 130 K, which
      contains the methyltransferase and helicase domains, using the baculovirus
      silkworm expression system and purified the recombinant protein to near
      homogeneity. Purified 130 K, which was stable in phosphate buffer containing
      magnesium ions and ATP, formed a dimer in solution and hydrolyzed nucleoside 5'
      triphosphates.

PMID- 30291969
TI  - Improving access to psychological therapies (IAPT) for people with bipolar
      disorder: Summary of outcomes from the IAPT demonstration site.
AB  - Access to structured psychological therapy recommended for bipolar disorder (BD)
      is poor. The UK NHS Improving Access to Psychological Therapies initiative
      commissioned a demonstration site for BD to explore the outcomes of routine
      delivery of psychological therapy in clinical practice, which this report
      summarises. All clinically diagnosed patients with BD who wanted a psychological
      intervention and were not in acute mood episode were eligible. Patients were
      offered a 10-session group intervention (Mood on Track) which delivered NICE
      congruent care. Outcomes were evaluated using an open (uncontrolled), pre-post
      design. Access to psychological therapy increased compared to preceding 6 years
      by 54%. 202 people began treatment; 81% completed >5 sessions; median 9 sessions
      (range 6-11). Pre-post outcomes included personal recovery (primary outcome),
      quality of life, work and social functioning, mood and anxiety symptoms
      (secondary outcomes). Personal recovery significantly improved from pre to post
      therapy; medium effect-size (d = 0.52). Secondary outcomes all improved (except
      mania symptoms) with smaller effect sizes (d = 0.20-0.39). Patient satisfaction
      was high. Use of crisis services, and acute admissions were reduced compared to
      pre-treatment. It is possible to deliver group psychological therapy for bipolar
      disorder in a routine NHS setting. Improvements were observed in personal
      recovery, symptoms and wider functioning with high patient satisfaction and
      reduced service use.

PMID- 30291970
TI  - The 24-hour serum profiles of bone markers in healthy older men and women.
AB  - The process of bone turnover displays variations over 24 h, with C-terminal cross
      linked telopeptide of type 1 collagen (CTX) and osteocalcin exhibiting a nadir in
      the afternoon and a peak in the night. In contrast, N-terminal propeptide of type
      1 procollagen (P1NP) did not display an apparent 24-hour rhythm. Other emerging
      novel biomarkers of bone, sclerostin and Dickkopf-related protein 1 (DKK1), are
      markers of osteocyte activity with limited data available regarding their 24-hour
      profiles. In this study, we aimed to extend available data on 24-hour profiles of
      CTX, osteocalcin, and P1NP and to assess the 24-hour profiles of sclerostin and
      DKK1 in healthy older men and women and to compare these between men and women.
      We measured these five bone markers in EDTA plasma collected every 4 h during 24
      h in 37 healthy older men and women (range 52-76 years). Differences between time
      points were determined using repeated measures ANOVA and cosinor analyses were
      performed to determine circadian rhythmicity. The circadian rhythm of CTX was
      confirmed by the cosinor model, with women showing larger amplitude compared to
      men. Osteocalcin showed higher levels during nighttime compared to daytime in
      both men and women. For P1NP levels we observed a small but significant increase
      in the night in men. Sclerostin and DKK1 did not show a circadian rhythm, but
      sclerostin levels differed between time points. Because of the large
      intraindividual variation, DKK1 as measured in this study cannot be considered a
      reliable marker for diagnostic or research purposes. In conclusion, when
      measuring CTX, osteocalcin, P1NP, or sclerostin either in clinical practice or in
      a research setting, one should consider the 24-hour profiles of these bone
      markers.

PMID- 30291971
TI  - Combining VITEK(r) 2 with colistin agar dilution screening assist timely
      reporting of colistin susceptibility.
AB  - OBJECTIVES: The rise in carbapenem resistance among Gram-negative bacteria has
      renewed interest in colistin. Recently, the EUCAST-CLSI Polymyxin Breakpoints
      Working Group declared that broth microdilution (BMD) is the only valid method
      for colistin susceptibility testing. BMD is not easily incorporated into the
      routine work of clinical laboratories, and usually this test is incorporated
      serially, resulting in delayed susceptibility reporting. We tested a strategy of
      combining VITEK(r) 2 with a 2 MUg/mL colistin agar dilution (VITEK(r) 2/AD)
      screening plate to improve performance and time to reporting of colistin
      susceptibility. METHODS: Colistin susceptibility for 364 clinical isolates was
      determined by VITEK(r) 2/AD and compared with the reference standard BMD
      according to the ISO 20776-1:2007 and CLSI guidelines. The EUCAST colistin
      susceptibility breakpoint of <=2 MUg/mL was used. Escherichia coli NCTC 13846
      served as quality control strain. Agreement, very major error (VME) and major
      error rates were determined using ISO 20776-2:2007. RESULTS: The VME rate for
      VITEK(r) 2 alone was 30.6% (15/49, 95% CI 18.3-45.4%), and was reduced to 10.2%
      (5/49, 95% CI 3.4-22.2%) using the VITEK(r) 2/AD combined testing. The combined
      testing had categorical agreement with BMD of 97% (354/364, 95% CI 95.0-98.7%),
      and a major error (ME) rate of 1.6% (5/315, 95% CI 0.5-3.7%). Using the combined
      testing, even against challenging strains, 349 (95.8%, 95% CI 93.3-97.7%)
      colistin susceptibility results could be reported, and only 15 isolates required
      further analysis by BMD. DISCUSSION: Our method is simple to apply and allows
      rapid reporting of colistin susceptibility.

PMID- 30291972
TI  - Changes in cognitive function among older adults: A latent profile transition
      analysis.
AB  - Cognitive decline in late life is a crucial health problem. It is important to
      understand the consistency and change of older adults' cognitive function in late
      life. Data for older adults (78 years and above) from the Health and Retirement
      Study (N = 1680) were used to explore meaningful subtypes of cognitive function
      and transitions patterns between those profiles across times. Age, gender, levels
      of education and nursing home were incorporated as covariates to explore the
      association between these variables and cognitive function transition pattern.
      Three cognitive function subgroups (Normal Cognitive Function, Fluid Intelligence
      Impairment and Cognitive Impairment) were identified. Individuals in Normal
      Cognitive Function status had a high probability to convert to the Fluid
      Intelligence Impairment status whereas the Cognitive Impairment status appeared a
      predominant tendency for stability. Increasing age played a significant role in
      fluid intelligence impairment and cognitive impairment process. Female and
      individuals with nursing home might be at higher risk of subsequent fluid
      intelligence impairment, while higher education did not protect against fluid
      intelligence impairment. These findings highlighted the usefulness to adopt a
      person-centered approach rather than a variable-centered approach, suggesting
      directions for future research and tailored interventions approaches to older
      adults with particular characteristics.

PMID- 30291974
TI  - Mapping the human brain's cortical-subcortical functional network organization.
AB  - Understanding complex systems such as the human brain requires characterization
      of the system's architecture across multiple levels of organization - from
      neurons, to local circuits, to brain regions, and ultimately large-scale brain
      networks. Here we focus on characterizing the human brain's large-scale network
      organization, as it provides an overall framework for the organization of all
      other levels. We developed a highly principled approach to identify cortical
      network communities at the level of functional systems, calibrating our community
      detection algorithm using extremely well-established sensory and motor systems as
      guides. Building on previous network partitions, we replicated and expanded upon
      well-known and recently-identified networks, including several higher-order
      cognitive networks such as a left-lateralized language network. We expanded these
      cortical networks to subcortex, revealing 358 highly-organized subcortical
      parcels that take part in forming whole-brain functional networks. Notably, the
      identified subcortical parcels are similar in number to a recent estimate of the
      number of cortical parcels (360). This whole-brain network atlas - released as an
      open resource for the neuroscience community - places all brain structures across
      both cortex and subcortex into a single large-scale functional framework, with
      the potential to facilitate a variety of studies investigating large-scale
      functional networks in health and disease.

PMID- 30291975
TI  - Multimodal evidence on shape and surface information in individual face
      processing.
AB  - The significance of shape and surface information for face perception is well
      established, yet their relative contribution to recognition and their neural
      underpinnings await clarification. Here, we employ image reconstruction to
      retrieve, assess and visualize such information using behavioral,
      electroencephalography and functional magnetic resonance imaging data. Our
      results indicate that both shape and surface information can be successfully
      recovered from each modality but that the latter is better recovered than the
      former, consistent with its key role for face representations. Further, shape and
      surface information exhibit similar spatiotemporal profiles, rely on the
      extraction of specific visual features, such as eye shape or skin tone, and
      reveal a systematic representational structure, albeit with more cross-modal
      consistency for shape than surface. More generally, the present work illustrates
      a novel approach to relating and comparing different modalities in terms of
      perceptual information content. Thus, our results help elucidate the
      representational basis of individual face recognition while, methodologically,
      they showcase the utility of image reconstruction and clarify its reliance on
      diagnostic visual information.

PMID- 30291973
TI  - Gustatory responses in macaque monkeys revealed with fMRI: Comments on taste,
      taste preference, and internal state.
AB  - Studies of the neural mechanisms underlying value-based decision making typically
      employ food or fluid rewards to motivate subjects to perform cognitive tasks.
      Rewards are often treated as interchangeable, but it is well known that the
      specific tastes of foods and fluids and the values associated with their taste
      sensations influence choices and contribute to overall levels of food
      consumption. Accordingly, we characterized the gustatory system in three macaque
      monkeys (Macaca mulatta) and examined whether gustatory responses were modulated
      by preferences and hydration status. To identify taste-responsive cortex, we
      delivered small quantities (0.1 ml) of sucrose (sweet), citric acid (sour), or
      distilled water in random order without any predictive cues while scanning
      monkeys using event-related fMRI. Neural effects were evaluated by using each
      session in each monkey as a data point in a second-level analysis. By contrasting
      BOLD responses to sweet and sour tastes with those from distilled water in a
      group level analysis, we identified taste responses in primary gustatory cortex
      area G, an adjacent portion of the anterior insular cortex, and prefrontal cortex
      area 12o. Choice tests administered outside the scanner revealed that all three
      monkeys strongly preferred sucrose to citric acid or water. BOLD responses in the
      ventral striatum, ventral pallidum, and amygdala reflected monkeys' preferences,
      with greater BOLD responses to sucrose than citric acid. Finally, we examined the
      influence of hydration level by contrasting BOLD responses to receipt of fluids
      when monkeys were thirsty and after ad libitum water consumption. BOLD responses
      in area G and area 12o in the left hemisphere were greater following full
      hydration. By contrast, BOLD responses in portions of medial frontal cortex were
      reduced after ad libitum water consumption. These findings highlight brain
      regions involved in representing taste, taste preference and internal state.

PMID- 30291976
TI  - A ready-to-use acidic, brushite-forming calcium phosphate cement.
AB  - Premixed calcium phosphate cements have been developed to simplify the usage of
      traditional calcium phosphate cements and reduce the influence of the setting
      reaction on the delivery process. However, difficulties in achieving a good
      cohesion, adequate shelf life and sufficient mechanical properties have so far
      impeded their use in clinical applications, especially for the more degradable
      acidic calcium phosphate cements. In this study, a brushite cement was developed
      from a series of ready-to-use calcium phosphate pastes. The brushite cement paste
      was formed via mixing of a monocalcium phosphate monohydrate (MCPM) paste and a
      beta-tricalcium phosphate (beta-TCP) paste with good injectability and adequate
      shelf life. The MCPM paste was based on a water-immiscible liquid with two
      surfactants and the beta-TCP paste on a sodium hyaluronate aqueous solution. The
      effect of citric acid as a retardant was assessed. Formulations with suitable
      amounts of citric acid showed good cohesion and mechanical performance with
      potential for future clinical applications. STATEMENT OF SIGNIFICANCE: Acidic
      calcium phosphate cements have attracted extensive attention as bone substitute
      materials due to their ability to resorb faster than basic calcium phosphate
      cements in vivo. However, traditionally, short working times and low mechanical
      strength have limited their clinical application. Premixed cements could simplify
      the clinical use as well as improve property reproducibility, but short shelf
      lives, low cohesion and low mechanical properties have restricted the
      development. In this study, an injectable ready-to-use two-phase system
      consisting of an MCPM paste and a beta-TCP paste was developed based on acidic
      cement. It shows good cohesion, compressive strength and adequate shelf life,
      which has the potential to be used in a dual chamber system for simplified and
      fast filling of bone defects in a minimally invasive manner. This will reduce
      surgery time, decrease the risk of contamination and ensure repeatable results.

PMID- 30291977
TI  - Antisynthetase syndrome and cardiac involvement: a rare association.

PMID- 30291978
TI  - Reply to the comment of Mourgues et al., 2012. American guidelines for the
      management of gout as seen by general practitioners.

PMID- 30291979
TI  - Reply to Misirlioglu et al: "Periscapular muscle ultrasound as a diagnostic aid
      in scapular winging secondary to long thoracic nerve lesion".

PMID- 30291980
TI  - Reply to the comment of Misirlioglu et al. "Periscapular muscle ultrasound as a
      diagnostic aid in scapular winging secondary to long thoracic nerve lesion".

PMID- 30291981
TI  - Potential role for microRNA in facilitating physiological adaptation to hypoxia
      in the Pacific whiteleg shrimp Litopenaeus vannamei.
AB  - Hypoxia is one of the most common physiological stressors in shrimp farming. Post
      transcriptional regulation by microRNAs has been recognized as a ubiquitous
      strategy to enable transient phenotypic plasticity and adaptation to stressful
      environment, but involvement of microRNAs in hypoxia stress response of penaeid
      shrimp remains elusive. In this study, small RNA sequencing and comparative
      transcriptomic analysis was conducted to construct a comprehensive microRNA
      dataset for the whiteleg shrimp Litopenaeus vannamei exposed to hypoxia
      challenge. A total of 3324 known miRNAs and 8 putative novel miRNAs were
      identified, providing a valuable resource for future investigation on the
      functional mechanism of miRNAs in shrimp. Upon hypoxia, 1213 miRNAs showed
      significant differential expression, and many well-known miRNAs involved in
      hypoxia tolerance such as miR-210, let-7, miR-143 and miR-101 were identified.
      Remarkably, the vast majority of these miRNAs were up-regulated, suggesting that
      up-regulation of miRNAs may represent an effective strategy to inhibit protein
      translation under stressful hypoxic condition. The differentially expressed
      miRNAs were potentially targeting a wide variety of genes, including those with
      essential roles in hypoxia tolerance such as HIF1a and p53. GO and KEGG
      enrichment analysis further revealed that a broad range of biological processes
      and metabolic pathways were over-represented. Several GO terms associated with
      gene transcription and translation and KEGG pathways related to cytoskeleton
      remodeling, immune defense and signaling transduction were enriched, highlighting
      the crucial roles of these cellular events in the adaptation to hypoxia. Taken
      together, our study revealed that the differentially expressed miRNAs may
      regulate host response to hypoxia by modulating the expression of stress response
      genes such as HIF1a and p53 and affecting key cellular events involved in hypoxia
      adaptation. The findings would expand our knowledge of the biochemical and
      molecular underpinnings of hypoxia response strategies used by penaeid shrimp,
      and contribute to a better understanding of the molecular mechanisms of hypoxia
      tolerance in decapod crustaceans.

PMID- 30291982
TI  - Phagocytosis and ROS production as biomarkers in Nile tilapia (Oreochromis
      niloticus) leukocytes by exposure to organophosphorus pesticides.
AB  - Organophosphorus pesticides (OPs) are broad-spectrum insecticides. One of the
      commonly used OPs is diazinon (DZN). The aim of this study was to evaluate the
      immunotoxic effect of DZN on phagocytic parameters of blood leukocytes using the
      teleost fish Oreochromis niloticus as a study model. For this purpose, fish were
      exposed in vivo to 0.97, 1.95 and 3.97 mg/L of DZN for 6 and 24 h. Our results
      indicated that phagocytic active cells decreased in fish exposed in vivo to 0.97
      and 1.95 mg/L of DZN for 6 and 24 h. Regarding ROS production, H2O2 and O2-
      levels were higher on fish exposed to 1.95 mg/L for 6 and 24 h, while H2O2
      production increased at 0.97 mg/L for 24 h. From this we can conclude that
      phagocytic parameters are sensitive to assess the effect of acute intoxication
      with organophosphorus pesticides on Nile tilapia.

PMID- 30291983
TI  - Effect of N-carbamoylglutamate supplementation on the growth performance,
      antioxidant status and immune response of mirror carp (Cyprinus carpio) fed an
      arginine-deficient diet.
AB  - The present study was conducted to determine the effect of dietary N
      carbamoylglutamate (NCG) supplementation on the growth performance, antioxidant
      capability and immune responses of mirror carp (Cyprinus carpio) fed an arginine
      (Arg)-deficient diet. A total of 630 mirror carp (41.65 +/- 0.14 g) were fed
      diets (Arg 1.24% of the diet) that were supplemented with 0.50% Arg (control
      diet) or graded levels of NCG at 0 (Arg deficiency diet), 0.04%, 0.08%, 0.12%,
      0.16% and 0.20% for 8 weeks. The results showed that, compared with the control
      diet, the Arg-deficient diet supplementation with 0 NCG (1) decreased the final
      body weight (FWB), the weight gain rate (WGR) or the protein efficiency ratio
      (PER) and increased the feed conversion ratio (FCR); (2) decreased the
      concentration of Arg and nitric oxide (NO) and the activity of total nitric oxide
      synthetase (T-NOS) in the plasma; (3) decreased the activities of superoxide
      dismutase (SOD) in the proximal intestine (PI), catalase (CAT) in the PI and
      distal intestine (DI), and glutathione peroxidase (GPx) in PI and mid-intestine
      (MI) and increased the concentration of malondialdehyde (MDA) in the PI, MI and
      DI; and (4) decreased the activity of lysozyme in the plasma, increased the
      relative mRNA expression of tumor necrosis factor-alpha (TNF-alpha),
      interleukin1beta (IL-1beta) and interleukin 8 (IL-8) in the PI, MI and DI, and
      decreased the relative mRNA expression of interleukin 10 (IL-10) in the PI and
      MI, and transforming growth factor beta2 (TGF-beta2) in the PI, MI and DI.
      Compared with the Arg deficient-diet supplementation with 0 NCG, (1) 0.12% or
      0.16% NCG increased the FBW, WGR and PER, and 0.16% NCG increased the FCR; (2)
      0.08%-0.20% NCG increased the concentration of Arg, NO and the activity of T-NOS;
      (3) 0.08% NCG increased the activities of SOD in the PI and MI, and 0.12% NCG
      increased activities of CAT and GPx in the PI, MI and DI; and (4) 0.04%-0.20% NCG
      increased the activity of lysozyme, 0.04%-0.20% NCG decreased the relative mRNA
      expression of TNF-alpha, IL-1beta and IL-8 in the PI and MI, and 0.04%-0.20% NCG
      increased the relative mRNA expression of IL-10 and TGF-beta2 in the PI and MI.
      The present results indicated that dietary 0.12% or 0.16% NCG improved the growth
      performance, feed utilization, intestinal antioxidant capacity and immune
      response of mirror carp fed an Arg-deficient diet.

PMID- 30291984
TI  - Changes of microRNAs expression profiles from red swamp crayfish (Procambarus
      clarkia) hemolymph exosomes in response to WSSV infection.
AB  - MicroRNAs (miRNAs) as short noncoding RNAs play important regulatory roles in
      diverse biological processes by degrading the target mRNAs, and could be
      delivered by exosomes. WSSV is a highly pathogenic and prevalent virus, and has
      brought high mortality of P. clarkia. Till present, no studies focus on the
      miRNAs changes in exosomes during WSSV infection. To understand the different
      virulence of WSSV on miRNAs expression in P. clarkia hemolymph exosome, the deep
      sequencing was performed to compare the small RNA libraries from the hemolymph
      exosome of P. clarkia individuals with or without WSSV infections. From the TEM
      observations, NTA and Western Blot analysis, the extracted exosomes were well
      identified with classic characteristics. The 209 conserved miRNAs and 250 novel
      miRNAs were identified from the small RNA libraries. In response to WSSV
      infection, there were about 98 miRNAs significantly up-regulated and 59 miRNAs
      significantly down-regulated. The target genes prediction, GO and KEGG enrichment
      analysis revealed that some target genes of P. clarkia miRNAs were grouped mainly
      into the categories of biological regulation, immune system process, signal
      pathway and other more functions. This is the first report of comprehensive
      identification of P. clarkia hemolymph exosome miRNAs being differentially
      regulated in response to WSSV infection. These results will help to understand
      the hemolymph exosome miRNAs response to different virulence WSSV infection.

PMID- 30291985
TI  - Transcriptomic analysis of immunoglobulin novel antigen receptor (IgNAR) heavy
      chain constant domains of brownbanded bamboo shark (Chiloscyllium punctatum).
AB  - Cartilaginous fish are the evolutionarily oldest group of animals which possess
      antibodies, T cell receptors and major histocompatibility complex (MHC). The
      immunoglobulin novel antigen receptor (IgNAR) found in cartilaginous fish is a
      heavy chain homodimer which lacks light chain. The presence of non-canonical
      cysteine molecules and lack of CDR2 region make it more significant. To
      synthesize active binding domains based on variable region of IgNAR (VNAR),
      knowledge on the constant region dynamics play a significant role. The IgNAR
      exhibit species variations in its primary sequence features; hence, this study
      was conducted to determine the IgNAR heavy chain constant domain of the
      brownbanded bamboo shark (Chiloscyllium punctatum). Peripheral blood leukocytes
      (PBL) isolated from adult bamboo sharks were used to synthesize a cDNA library. A
      total of four billion residues of two million sequences (average length 218.41
      bp) were obtained. Assembled sequences were aligned with published cartilaginous
      fish IgNAR constant region sequences. Transcriptome analysis revealed two
      distinct types of IgNAR in the brownbanded bamboo shark. Also, constant-1 domain
      sequences displayed 13 unique sequences which may reflect the least number of
      IgNAR gene clusters. The phylogenetic analysis revealed the closest relationship
      with the nurse shark (Ginglymostoma cirratum) followed by the wobbegong shark
      (Orectolobus maculatus) which belong to the same order Orectolobiformes. Analysis
      of the constant domains of the brownbanded bamboo shark IgNAR revealed an
      evolutionarily conserved nature and this knowledge can be used to design primers
      for VNAR cloning. Furthermore, knowledge on the structural features in IgNAR
      constant domains that increase the stability could be useful in the process of
      stabilizing human immunoglobulins.

PMID- 30291986
TI  - Chelation, formulation, encapsulation, retention, and in vivo biodistribution of
      hydrophobic nanoparticles labelled with 57Co-porphyrin: Oleylamine ensures stable
      chelation of cobalt in nanoparticles that accumulate in tumors.
AB  - BACKGROUND AND MOTIVATION: While small molecules can be used in cancer diagnosis
      there is a need for imageable diagnostic NanoParticles (NPs) that act as
      surrogates for the therapeutic NPs. Many NPs are composed of hydrophobic
      materials so the challenge is to formulate hydrophobic imaging agents. To develop
      individualized medical treatments based on NP, a first step should be the
      selection of patients who are likely responders to the treatment as judged by
      imaging tumor accumulation of NPs. This requires NPs with the same size and
      structure as the subsequent therapeutic NPs but labelled with a long-lived
      radionuclide. Cobalt isotopes are good candidates for NP labelling since 55Co has
      half-life of 17.5 h and positron energy of 570 keV while 57Co (t1/2 271.6 d) is
      an isotope suited for preclinical single photon emission tomography (SPECT) to
      visualize biodistribution and pharmacokinetics of NPs. We used the hydrophobic
      octaethyl porphyrin (OEP) to chelate cobalt and to encapsulate it inside
      hydrophobic liquid NPs (LNPs). We hypothesized that at least two additional
      hydrophobic axial ligands (oleylamine, OA) must be provided to the OEP-Co complex
      in order to encapsulate and retain Co inside LNP. RESULTS: 1. Cobalt chelation by
      OEP and OA. The association constant of cobalt to OEP was 2.49 * 105 M-1 and the
      formation of the hexacoordinate complex OEP-Co-4OA was measured by spectroscopy.
      2. NP formulation and characterization: LNPs were prepared by the fast ethanol
      injection method and were composed of a liquid core (triolein) surrounded by a
      lipid monolayer (DSPC:Cholesterol:DSPE-PEG2000). The size of the LNPs loaded with
      the cobalt complex was 40 +/- 5 nm, 3. Encapsulation of OEP-Co-OA: The loading
      capacity of OEP-Co-OA in LNP was 5 mol%. 4. Retention of OEP-57Co-4OA complex in
      the LNPs: the positive effect of the OA ligands was demonstrated on the stability
      of the OEP-57Co-4OA complex, providing a half-life for retention in PBS of 170 h
      (7 days) while in the absence of the axial OA ligands was only 22 h. 5
      Biodistribution Study: the in vivo biodistribution of LNP was studied in AR42J
      pancreatic tumor-bearing mice. The estimated half-life of LNPs in blood was about
      7.2 h. Remarkably, the accumulation of LNPs in the tumor was as high as 9.4% ID/g
      24 h after injection with a doubling time for tumor accumulation of 3.22 h. The
      most important result was that the nanoparticles could indeed accumulate in the
      AR42J tumors up to levels greater than those of other NPs previously measured in
      the same tumor model, and at about half the values reported for the molecular
      agent 57Co-DOTATATE. CONCLUSIONS: The additional hydrophobic chelator OA was
      indeed needed to obtain a stable octahedral OEP-Co-4OA. Cobalt was actually well
      retained inside LNP in the OEP-Co-4OA complex. The method described in the
      present work for the core-labelling of LNPs with cobalt is now ready for labeling
      of NPs with 55Co, or indeed other hexadentate radionuclides of interest for
      preclinical in vivo PET-imaging and radio-therapeutics.

PMID- 30291987
TI  - Lipid conjugation of TLR7 agonist Resiquimod ensures co-delivery with the
      liposomal Cationic Adjuvant Formulation 01 (CAF01) but does not enhance
      immunopotentiation compared to non-conjugated Resiquimod+CAF01.
AB  - Pattern recognition receptors, including the Toll-like receptors (TLRs), are
      important in the induction and activation of two critical arms of the host
      defence to pathogens and microorganisms: the rapid innate immune response (as
      characterised by the production of Th1 promoting cytokines and type 1
      interferons) and the adaptive immune response. Through this activation, ligands
      and agonists of TLRs can enhance immunotherapeutic efficacy. Resiquimod is a
      small (water-soluble) agonist of the endosome-located Toll-like receptors 7 and 8
      (TLR7/8). However due to its molecular attributes it rapidly distributes
      throughout the body after injection. To circumvent this, these TLR agonists can
      be incorporated within delivery systems, such as liposomes, to promote the co
      delivery of both antigen and agonists to antigen presenting cells. In this
      present study, resiquimod has been chemically conjugated to a lipid to form a
      lipid-TLR7/8 agonist conjugate which can be incorporated within immunogenic
      cationic liposomes composed of dimethyldioctadecylammonium bromide (DDA) and the
      immunostimulatory glycolipid trehalose 6,6' - dibehenate (TDB). This DDA:TDB
      TLR7/8 formulation offers similar vesicle characteristics to DDA:TDB (size and
      charge) and offers high retention of both resiquimod and the electrostatically
      adsorbed TB subunit antigen Ag85B-ESAT6-Rv2660c (H56). Following immunisation
      through the intramuscular (i.m.) route, these cationic DDA:TDB-TLR7/8 liposomes
      form a vaccine depot at the injection site. However, immunisation studies have
      shown that this biodistribution does not translate into notably increased
      antibody nor Th1 responses at the spleen and draining popliteal lymph node
      compared to DDA:TDB liposomes. This work demonstrates that the conjugation of
      TLR7/8 agonists to cationic liposomes can promote co-delivery but the immune
      responses stimulated do not merit the added complexity considerations of the
      formulation.

PMID- 30291988
TI  - Stress, female reproduction and pregnancy.
AB  - Stress is one of the commonest and underappreciated causes of reproductive
      frailty in women. The stress system leads to adaptive responses via mobilization
      of hormonal systems. Adaptability and resistance to stress are fundamental to
      life. The response to stressors depends on the type of stressor, the timing and
      duration of stress, the genetic predisposition, personality characteristics, and
      the way of coping with stress. The hypothalamic-pituitary-adrenal (HPA) axis has
      a direct inhibitory action on the hypothalamic-pituitary-ovarian (HPO) axis at
      multiple levels. Acute and chronic stress impairs reproduction, eventually acting
      on varying mechanisms. Undernutrition, over-training, and psychological stress
      contribute to hypothalamic amenorrhea via reduced HPO activity. In utero stress
      exposure is a significant predictor of subsequent adult telomere length. Some of
      the metabolic consequences of intrauterine growth restriction can be mitigated by
      ensuring early appropriate catch-up growth, while avoiding excessive weight gain
      if relative hypercortisolism is not installed. The effect of maternal stress on
      fetuses regarding fetal HPA axis responsiveness (increased or decreased) remains
      under investigation. Maternal stress and depression are associated with
      structural and functional changes of brain parts such as hippocampus. In utero
      stress modifies epigenetically components of the HPA axis which can be
      transmitted transgenerationally.

PMID- 30291989
TI  - Multi-omics analysis: Repeated exposure of a 3D bronchial tissue culture to whole
      cigarette smoke.
AB  - Cigarette smoke (CS) is a major risk factor in the development of chronic
      inflammatory lung diseases such as chronic obstructive pulmonary disease. A
      comprehensive investigation of the biological impacts of chronic CS exposure on
      lung tissue is therefore important for understanding the pathogenesis of lung
      disease. We used three-dimensional (3D) organotypic human bronchial tissue
      cultures and metabolomics, transcriptomics, and proteomics to investigate changes
      in biological processes affected by repeated whole-CS exposure. We found that CS
      perturbed central carbon metabolism in relation with oxidative stress responses.
      Epidermal growth factor receptor, which is involved in the early-stage
      pathogenesis of airway diseases, was identified as a key regulator of the
      perturbed processes. Proteomic analysis of proteins in the apical surface liquid
      of the 3D bronchial tissue cultures indicated that repeated whole-CS exposure
      induced alterations in the secretion of several known biomarkers of airway
      diseases, including mucins and matrix metalloproteinases. These findings are
      consistent with observations from lung disease patients. Overall, our results
      suggest that 3D bronchial tissue cultures can provide valuable information on
      tissue-specific alterations in biological processes induced by chronic exposure
      to CS.

PMID- 30291990
TI  - SkinEthicTM HCE Eye Irritation Test: Similar performance demonstrated after long
      distance shipment and extended storage conditions.
AB  - Assessment of ocular irritation risk is an international regulatory requirement
      in the safety evaluation of products. In response to this need, L'Oreal developed
      the SkinEthicTM Human Corneal Epithelium (HCE) Eye Irritation Test (EIT) that has
      been included in OECD Test Guideline 492. SkinEthicTM HCE EIT is able to
      correctly and reliably identify chemicals not requiring classification versus
      labelling for eye irritation or serious eye damage according to UN GHS. In an
      effort to promote its global use, the performance of the method was evaluated
      after long-distance shipment and compared to European shipment conditions.
      Results obtained by Cosmos Technical Center (Japan) after extended tissues
      transit were compared to results obtained in L'Oreal (France). Thirty-nine out of
      40 blinded chemicals, representing different functional chemical classes, were
      consistently classified in both laboratories. The SkinEthicTM HCE EIT test method
      was also evaluated for its performance after extended storage of the tissues. The
      performance was in agreement with the values reported in OECD TG 492, with an
      overall accuracy of 87.1% (based on 119 chemicals), sensitivity of 95.5% and
      specificity of 73.5%. The reliability and relevance of SkinEthicTM HCE EIT test
      method after long-distance shipment and extended storage remain in agreement with
      regulatory validation criteria.

PMID- 30291991
TI  - Microplastic testing in vitro: Realistic loading of pollutants, surfactant-free
      solid surface-dosing and bioanalytical detection using a sensitivity-optimized
      EROD assay.
AB  - Microplastic particles (MPs) are emerging contaminants in aquatic environments,
      which are assumed to play a role as vectors for lipophilic pollutants, as the
      particles bear a potential for the accumulation of lipophilic contaminants from
      the water phase on the MPs' surface and subsequent release in contact with
      organisms. In an attempt to allow the bioanalytical detection and quantitatively
      estimate bioavailability of MP-bound pollutants under realistic conditions in
      vitro, a protocol was developed for water-based loading of lipophilic substances
      to MPs using a solid-phase extraction (SPE) approach and subsequent detection of
      the substances in a sensitivity-enhanced 7-ethoxyresorufin-O-deethylase (EROD)
      assay with RTL-W1 cells. Exemplarily, particles were loaded with
      benzo[k]fluoranthene (BkF), which was shown to bind to MPs with high affinity.
      Spiked particles were added to the surface of the culture medium, where they
      released low, but consistent amounts of BkF, which were quantified by EROD
      induction. Additionally, a geometrical model was developed for the estimation of
      numbers, surface areas and masses of MPs interacting with medium. The approach
      presented allows the experimental in vitro examination of the postulated function
      of MP as a pollutant vector in a highly sensitive animal-experimentation-free
      test system.

PMID- 30291992
TI  - Influence of distortions of recorded diffraction patterns on strain analysis by
      nano-beam electron diffraction.
AB  - Images acquired in transmission electron microscopes can be distorted for various
      reasons such as e.g. aberrations of the lenses of the imaging system or
      inaccuracies of the image recording system. This results in inaccuracies of
      measures obtained from the distorted images. Here we report on measurement and
      correction of elliptical distortions of diffraction patterns. The effect of this
      correction on the measurement of crystal lattice strain is investigated. We show
      that the effect of the distortions is smaller than the precision of the
      measurement in cases where the strain is obtained from shifts of diffracted discs
      with respect to their positions in images acquired in an unstrained reference
      area of the sample. This can be explained by the fact that diffraction patterns
      acquired in the strain free reference area of the sample are distorted in the
      same manner as the diffraction patterns acquired in the strained region of
      interest. In contrast, for samples without a strain free reference region such as
      nanoparticles or nanoporous structures, where we evaluate ratios of lattice plane
      distances along different directions, the distortions are usually not negligible.
      Furthermore, two techniques for the detection of diffraction disc positions are
      compared showing that for samples in which the crystal orientation changes over
      the investigated area it is more precise to detect the positions of many
      diffraction discs simultaneously instead of detecting each disc position
      independently.

PMID- 30291993
TI  - Disseminated tumor cells predict efficacy of regional nodal irradiation in early
      stage breast cancer.
AB  - BACKGROUND: The disseminated tumor cells (DTC) are collected in the bone marrow
      and are the witness of micrometastatic spread. We previously reported that DTC
      could be a predictive factor of the efficacy of regional node irradiation
      (IMN/SCN: internal mammary nodes & supra-infra clavicular nodes). In this
      article, we report the long-term results (>10 years) on the impact of DTC status
      in early-stage breast cancer. METHODS: Patients with localized breast cancer were
      eligible for this prospective cohort. DTC was obtained from a medullary iliac
      crest sample performed prior to any primary therapy. DTC status was prospectively
      assessed by pathologists. Irradiation volumes were defined per standard of care.
      Cumulative incidence rates and hazard ratio were obtained using both Cox and Fine
      Gray models. Interaction tests were performed to confirm the predictive value of
      DTC status in a multivariate analysis. RESULTS: 620 patients with localized
      breast cancer were included. Overall, 94 patients (15.2%) were DTC-positive.
      After a median follow-up of 11.7 years, 47 patients (7.6%) experienced a
      locoregional relapse. DTC detection was associated with a higher risk of
      locoregional relapse in univariate and multivariate analyses (Cox, HR=3.26,
      95%CI=[1.6;5.7], p=0.001). In the multivariate subgroup analysis, IMN/SCN
      irradiation significantly reduced locoregional relapse for DTC-positive patients
      comparing to DTC-negative patients (interaction test: HR=0.3, 95%CI [0.1;0.9],
      p=0.02). IMN/SCN was the only irradiation volume with a impact on locoregional
      relapse in patients, according to their DTC status, and the predictive value of
      DTC status for the benefit of locoregional irradiation was independent of the
      locoregional nodal status. CONCLUSION: This long-term analysis confirms the
      predictive impact of DTC status on the efficacy of regional radiotherapy on
      locoregional relapse in early breast cancer. After further studies, DTC status
      could be a decision tool to better tailor adjuvant radiation therapy in early
      stage breast cancer patients.

PMID- 30291994
TI  - Validation of Effective Dose as a Better Predictor of Radiation Pneumonitis Risk
      than Mean Lung Dose: Secondary Analysis of a Randomized Trial.
AB  - PURPOSE: To confirm the superiority of effective dose (Deff) over mean lung dose
      (MLD) for predicting risk of radiation pneumonitis (RP), using data from patients
      on a randomized trial of intensity-modulated radiotherapy (IMRT) versus passively
      scattered proton therapy (PSPT). METHODS: The prescribed target dose for the 203
      evaluated patients was 66-74 Gy(RBE) in 33-37 fractions with concurrent
      carboplatin/paclitaxel. Time to grade >2 RP was computed from the start of
      radiotherapy, with disease recurrence or death considered censoring events.
      Generalized Lyman models of censored time to RP were constructed with MLD or Deff
      as the dosimetric parameter. Smoking status (current, former, never) was also
      analyzed. RESULTS: Of the 203 patients, 46 experienced grade >=2 RP (crude
      incidence 23%), at a median 3.7 months (range, 0.6-12.6 months). The volume
      parameter estimated for the Deff model was n=0.5, confirming estimates from
      earlier studies. Compared with MLD (in which n=1), the dosimetric parameter Deff,
      computed using n=0.5, resulted in a better fit of the Lyman model to the clinical
      data (P=0.010). Using Deff, the model describes RP risk for IMRT and PSPT data
      combined, as no further improvement was found from separate fits (P=0.558). Based
      on Deff, predicted RP risk per patient ranged from 24 percentage points lower to
      19 percentage points higher than predictions based on MLD. For patients with
      similar MLD, Deff predicted higher risk, on average, for PSPT over IMRT. Current
      smokers had a lower risk of RP than former smokers and nonsmokers (P=0.021).
      CONCLUSIONS: We used data from a randomized trial to validate our previous
      finding that Deff with n=0.5 (corresponding to root mean squared dose) is a
      better predictor of RP than MLD. Differences between Deff and MLD indicate that
      delivering higher doses to smaller lung volumes (vs. lower doses to larger
      volumes) increases RP risk. We further corroborated that current smoking is
      associated with decreased RP risk.

PMID- 30291995
TI  - Treatment of diverticular disease, targeting symptoms or underlying mechanisms.
AB  - Diverticular disease (DD) is a highly prevalent disease in western industrialized
      countries that encompasses a complex set of disorders. Because of its complexity
      and heterogeneity, both from a pathogenic and a clinical point of view, the
      management of this disease represent a challenge in clinical practice. This
      review aims to analyze and summarize the most recent evidence on the medical
      strategies for DD, considering separately the different stages of the disease,
      from prevention of diverticula formation to treatment of acute diverticulitis and
      prevention of recurrences. Based on some evidence, dietary fiber is useful to
      prevent diverticula formation and in diverticulosis, with no pharmacological
      treatment in these settings. Treatment of symptomatic uncomplicated diverticular
      disease as well as primary prevention of acute diverticulitis is based on
      probiotics, fibres, mesalazine and rifaximin, individually or as combination
      therapy, although a standard approach has not yet been defined. On the contrary,
      in acute diverticulitis (AD) recent acquisitions have clarified and standardized
      the role of systemic antibiotics, reserving its use only to complicated forms and
      in selected cases of uncomplicated disease. Secondary prevention of AD is
      essentially based on mesalazine and rifaximin but, despite promising results, no
      strong evidence have been produced. To date, grey areas remain in the medical
      management of DD.

PMID- 30291996
TI  - Altered composition of the gut microbiome in patients with drug-resistant
      epilepsy.
AB  - OBJECTIVE: The relationship between the gut microbiota and the central nervous
      system has been gradually recognized while whether microbiome plays a role in the
      pathogenesis of drug-resistant epilepsy is still unknown. The aim of our work was
      to explore whether dysbiosis is involved in the mechanism of drug-resistant
      epilepsy. METHODS: Patients with epilepsy attending West China Hospital of
      Sichuan University were enrolled from March to May 2017. Patients were grouped
      into drug-resistant (n = 42) and drug-sensitive (n = 49) groups, another 65
      healthy controls were from the same families of the patients. The fecal samples
      were collected and the microbiome composition was analyzed by high-throughout
      sequencing of the 16s ribosomal DNA. RESULTS: We found that the gut microbial
      community of drug-resistant epilepsy was significantly altered with an abnormal
      increased abundance of rare flora. While the gut microbiome composition of drug
      sensitive epilepsy was similar with that of healthy controls. Specifically,
      patients with four seizures per year or fewer showed an increase of
      Bifidobacteria and Lactobacillus than those with more than four seizures per
      year. CONCLUSIONS: Dysbiosis may be involved in the mechanism of drug-resistant
      epilepsy and restoring the gut microbial community may be a novel therapeutic
      method for drug-resistant epilepsy.

PMID- 30291997
TI  - Implementing community health worker-patient pairings at the time of hospital
      discharge: A randomized control trial.
AB  - BACKGROUND: In 2011, there were approximately 3.3 million adult 30-day all-cause
      hospital readmissions in the US generating $41.3 billion in hospital costs.
      Community health worker (CHW) care delivery is one of very few interventions
      demonstrated to reduce health care utilization among populations with chronic
      disease. While there are a number of studies demonstrating improved disease
      specific outcomes with CHW interventions, studies examining the effect of CHW
      care delivery on 30-day readmission rates are rare. METHODS: This study is a
      randomized control trial designed to determine if linking hospitalized patients
      with chronic disease to community health workers (CHWs) can decrease 30-day
      readmissions. Participants were randomly assigned to receive the 30-day CHW
      intervention or usual care (no CHW). All study participants completed surveys at
      baseline and the end of the study 30 days post-discharge. The primary outcome was
      30-day readmission and secondary outcomes included emergency department visits,
      missed appointments, and patient satisfaction. RESULTS: We plan to enroll 1200
      hospitalized patients during a 24-month intervals. As of December 2017, 350
      patients have been consented and randomly assigned to either the intervention or
      control arm. A number of challenges have been encountered in implementing a CHW
      initiative at the time of hospital discharge. CONCLUSION: This trial tests the
      effectiveness of CHW care delivery at the time of hospital discharge in reducing
      30-day readmission rates and improving outcomes among patients with chronic
      disease. We describe and discuss challenges in launching this CHW intervention
      and strategies utilized to overcome these obstacles. Clinical Trials.gov
      registration submitted 3/14/2017: Protocol ID# 2017A050810 and Clinical
      Trials.gov ID# NCT03085264 Community Health Worker Care Transitions Study (C
      CAT).

PMID- 30291998
TI  - Moms fit 2 fight: Rationale, design, and analysis plan of a behavioral weight
      management intervention for pregnant and postpartum women in the U.S. military.

PMID- 30291999
TI  - Interaction of Group B Streptococcus sialylated capsular polysaccharides with
      host Siglec-like molecules dampens the inflammatory response in tilapia.
AB  - Group B Streptococcus (GBS, S. agalactiae) infection in tilapia (Oreochromis
      niloticus) causes widespread death of this species and is a significant issue for
      the aquaculture industry. The major virulence factor for GBS is its sialylated
      capsular polysaccharides (CPs). These CPs interact with sialic acid-binding
      immunoglobulin-like lectins (Siglecs) on the host immune cells to regulate the
      downstream inflammatory response and evade detection. Previously, we cloned
      multiple Siglec-like molecules from an O. niloticus cDNA library, all of which
      were shown to interact with the sialylated CPs of GBS. In the present study, we
      investigated the effects of GBS infection on the expression of pro- and anti
      inflammatory cytokines in O. niloticus as well as OnSiglec-like-transfected
      macrophage cells. Eukaryotic expression vectors containing full-length OnSiglec-1
      like, -4b-like, -14-like were constructed and used to transfect RAW264
      macrophages in vitro as well as live tilapia in vivo prior to GBS infection. The
      expression of the anti-inflammatory cytokine interleukin (IL)-10 and the pro
      inflammatory cytokines tumor necrosis factor (TNF)-alpha, IL-6, and interferon
      (INF)-beta were then analyzed by qPCR. Our results indicate that as infection
      progressed, IL-10 expression was significantly upregulated, while that of TNF
      alpha and IL-6 were significantly downregulated in the OnSiglec-like-transfected
      cells. INF-beta expression was also downregulated in cells transfected with
      OnSiglec-1-like and -4b-like, but was not significantly effected in OnSiglec-14
      like-transfected cells. Notably, the magnitude of these cytokine expression
      changes was greatly decreased when a DeltaneuA GBS mutant was used to infect the
      OnSiglec-1-like-transfected cells. In GBS-infected tilapia, IL-10 expression was
      significantly upregulated in all tissues, whereas INF-beta expression in the
      spleen, kidney, and gills was significantly downregulated at 12 hpi. While the
      expression of TNF-alpha was slightly upregulated, this change was not
      significant. In GBS DeltaneuA mutant-infected O. niloticus, IL-10 expression in
      all of the tissues was significantly lower than that observed for the wild-type
      GBS group, while TNF-alpha expression was higher in the mutant infected group.
      There was no significant difference in INF-beta expression between the two
      groups. Taken together, sialylated CPs on GBS appear to interact with host
      OnSiglec-like molecules to transmit negative regulatory signals via enhanced anti
      inflammatory cytokine IL-10 production and reduced pro-inflammatory cytokine
      production, ultimately leading to dampening of the host immune response. The
      results of this study further elucidate the molecular mechanism underlying GBS
      infection in tilapia and also provide candidate drug target molecules.

PMID- 30292000
TI  - Incidence of postoperative nausea and vomiting after laparoscopic sleeve
      gastrectomy with staple line reinforcement with oversewing and staple line
      inversion vs buttressing material: A randomized clinical trial.
AB  - BACKGROUND: Postoperative nausea and vomiting are relevant complications after
      restrictive bariatric procedures, such as sleeve gastrectomy, mainly secondary to
      a drastic reduction in the gastric volume. However, other causes can be involved.
      The aim of this study was to determine the incidence of postoperative nausea and
      vomiting (PONV) after laparoscopic sleeve gastrectomy (LSG), with staple line
      reinforcement with oversewing vs buttressing material. PATIENTS AND METHODS: A
      prospective randomized clinical trial of all the patients undergoing LSG was
      performed. Patients were divided into 2 groups: patients undergoing staple line
      inversion (Group 1) and patients undergoing staple line reinforcement with
      buttressing material (Group 2). Nausea and vomiting were assessed by the
      Postoperative Nausea and Vomiting Intensity Scale. RESULTS: A total of 100
      females were included in the study, 50 in each group. Mean operative time was
      66.1 +/- 11.6 min in Group 1 and 55.4 +/- 9.4 in Group 2 (p < 0.001). There were
      no significant differences in staple line leaks and bleeds between groups. The
      PONV intensity score at 6 h was 316.4 in Group 1 and 77.1 in Group 2 (p < 0.001).
      24 h after surgery, the PONV intensity score was 86 in Group 1 and 7.9 in Group 2
      (p = 0.022). CONCLUSION: The reinforcement with a running suture in LSG creates
      more PONV and increases the duration of the symptoms during the first hours after
      surgery, and prevents from early oral intake in a greater number of cases, when
      compared with the use of buttressing material as reinforcement method.

PMID- 30292001
TI  - The efficacy and safety of parecoxib for reducing pain and opioid consumption
      following total knee arthroplasty: A meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: The goal of the current meta-analysis is to make a credible and
      overall assessment about the efficacy and safety of parenteral parecoxib for pain
      control in total knee arthroplasty (TKA). METHODS: The following online
      electronic databases, such as PubMed, Cochrane, Embase, were searched to identify
      the qualified studies updated to August 2018 according to the index words. Weight
      mean difference (WMD) or risk difference (RD) along with 95% confidence interval
      (CI) was utilized to analyze the main outcomes. To assess the heterogeneity of
      study trial and determine the model for analysis (random-effect model or fixed
      effect model), I2 tests and Chi-squared were conducted. We utilized the STATA
      10.0 (TX, USA) to perform all statistical analyses. RESULT: Totally, four studies
      were involved in the meta-analysis with 418 patients. The present meta-analysis
      indicated that intravenous parecoxib was associated with a significantly improved
      pain relief and opioid consumption after TKA. There was no increased risk of
      adverse effects related to parecoxib. CONCLUSION: Intravenous parecoxib is
      effective in reducing knee pain and opioid consumption in patient with TKA.
      Further well-designed research with large simple sizes is necessary to confirm
      our conclusion.

PMID- 30292002
TI  - A novel hybrid fixation (coracoclavicular screw supplemented with K-wire) for the
      treatment of acute acromioclavicular joint dislocation: A prospective study.
AB  - OBJECTIVE: The aim of this study was to compare the radiological and clinical
      outcomes of clavicular hook plate fixation and the coracoclavicular lag screw
      supplemented with K-wire fixation in the treatment of acute acromioclavicular
      joint dislocation. METHODS: Between January 2012 to December 2015, 81 patients
      with acute acromioclavicular joint dislocation were included in this prospective
      study. 43 patients were treated with clavicular hook plate fixation (Group A) and
      38 patients were treated with coracoclavicular lag screw supplemented with K-wire
      fixation (Group B). Incision length, operation duration, blood loss volume,
      intraoperative fluoroscopy times and length of hospitalization were recorded.
      Radiographic outcomes, functional outcomes and complications were also recorded.
      RESULTS: Both two groups could achieve good radiographic and functional outcomes
      after operation. Group B exhibited significantly shorter operation duration,
      shorter length of incision, less blood loss volume and shorter length of
      hospitalization than Group A (P < 0.001). In addition, significant difference
      could be found between the two groups regarding the VAS scores three month
      postoperatively and the final follow-up (P < 0.001). However, there was no
      significant difference in radiographic and functional outcomes between the two
      groups (P > 0.05). CONCLUSION: The two groups can both achieve satisfactory
      radiological and functional outcomes in treating acute AC joint dislocation.
      However, CC screw fixation supplemented with K-wire exerts some advantages
      regarding the incision length, operation duration, blood loss volume, length of
      hospitalization. Furthermore, it can better relieve the pain caused by
      dislocation. Therefore, the novel hybrid fixation (CC screw fixation supplemented
      with K-wire) provides an alternative treatment for acute AC joint dislocation.

PMID- 30292003
TI  - Polarization inversion applied to proton MAS-NMR spectroscopy - Methylene and
      methine free proton NMR spectra.
AB  - Polarization-inversion (PI) has been applied to proton magic angle spinning (MAS)
      NMR spectra recorded under fast MAS conditions. The combination of cross
      polarization (CP) from carbon to proton and subsequent polarization-inversion
      produces strong oscillatory behavior in the proton signal intensities at high MAS
      speeds of 60 kHz. It is observed that by a suitable choice of the polarization
      inversion time, a proton spectrum free of methylene and methine protons can be
      obtained. Such a spectrum, on the one hand, increases the resolution of the
      crowded proton spectrum and on the other hand provides exclusively chemical
      shifts of protons such as NH, OH and SH which might otherwise overlap with carbon
      attached protons. The oscillations observed during PI can also be used to
      estimate the dipolar coupling between proton and carbon by Fourier transformation
      of data acquired at equally incremented time periods. The utility of the above
      ideas has been demonstrated on a set of molecules with both 13C labeled and 13C
      in natural abundance.

PMID- 30292004
TI  - Mineralogy and buffer identity effects on RDX kinetics and intermediates during
      reaction with natural and synthetic magnetite.
AB  - Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is known to undergo reduction
      mediated by ferrous iron in the presence of minerals, including magnetite.
      Idealized laboratory conditions may not provide representative reaction kinetics
      or pathways compared to field conditions. The effects of magnetite mineral
      morphology, the aquifer material matrix, the presence of aqueous Fe(II), and the
      buffer identity on RDX reduction kinetics and intermediate formation are
      investigated in this work. Reactions in bicarbonate buffer were substantially
      slower than those performed in 3-(N-morpholino)propanesulfonic acid (MOPS)
      buffer, and the presence of quartz and clays in magnetite-containing aquifer
      material resulted in slower reaction kinetics and production of additional iron
      oxide phases. Buffer identity also changed the rate controlling step and reaction
      product distribution. Conditions as close to those expected in field systems are
      necessary to evaluate the reaction rates and pathways of RDX in reduced
      groundwater systems.

PMID- 30292005
TI  - Trace elements in the cycle of soils, sediments, waters, and plants: Editorial to
      the special issue.

PMID- 30292006
TI  - Virus detection in high-throughput sequencing data without a reference genome of
      the host.
AB  - Discovery of novel viruses in host samples is a multidisciplinary process which
      relies increasingly on next-generation sequencing (NGS) followed by computational
      analysis. A crucial step in this analysis is to separate host sequence reads from
      the sequence reads of the virus to be discovered. This becomes especially
      difficult if no reference genome of the host is available. Furthermore, if the
      total number of viral reads in a sample is low, de novo assembly of a virus which
      is a requirement for most existing pipelines is hard to realize. We present a new
      modular, computational pipeline for discovery of novel viruses in host samples.
      While existing pipelines rely on the availability of the hosts reference genome
      for filtering sequence reads, our new pipeline can also cope with cases for which
      no reference genome is available. As a further novelty of our method a decoy
      module is used to assess false classification rates in the discovery process.
      Additionally, viruses with a low read coverage can be identified and visually
      reviewed. We validate our pipeline on simulated data as well as two experimental
      samples with known virus content. For the experimental samples, we were able to
      reproduce the laboratory findings. Our newly developed pipeline is applicable for
      virus detection in a wide range of host species. The three modules we present can
      either be incorporated individually in other pipelines or be used as a stand
      alone pipeline. We are the first to present a decoy approach within a virus
      detection pipeline that can be used to assess error rates so that the quality of
      the final result can be judged. We provide an implementation of our modules via
      Github. However, the principle of the modules can easily be re-implemented by
      other researchers.

PMID- 30292007
TI  - Mutations of Mycobacterium tuberculosis induced by anti-tuberculosis treatment
      result in metabolism changes and elevation of ethambutol resistance.
AB  - Selective pressure from antibiotic use is one of the most important risk factors
      associated with the development of drug resistance in Mycobacterium tuberculosis
      (MTB). However, the mechanisms underlying drug resistance at the molecular level
      remain partly unclear. Therefore, the purpose of this study was to investigate
      the potential functional effect of novel mutations arising from anti-tuberculosis
      treatment. We analyzed two multidrug-resistant TB (MDR-TB) isolates from the same
      patient; one collected before and one almost a year after commencing MDR-TB
      treatment. The post-treatment isolate exhibited elevated ethambutol resistance.
      We sequenced the whole genomes of the two clinical isolates and detected six
      novel polymorphisms affecting the genes Rv1026, nc0021, Rv2155c, Rv2437, and
      Rv3696c, and the intergenic region between Rv2764c and Rv2765. Metabolomics
      approach was used to reveal the effect of the found variation on the metabolic
      pathways of MTB. Partial least squares-discriminant analysis showed a clear
      differentiation between the two isolates, involving a total of 175 metabolites.
      Pathway analysis showed that these metabolites are mainly involved in amino sugar
      and nucleotide sugar metabolism, beta-alanine metabolism, sulfur metabolism, and
      galactose metabolism. The increased ethambutol resistance exhibited by the post
      treatment MDR-TB strain could speculatively be linked to the identified genetic
      variations, which affected the synthesis of a number of metabolites associated
      with sources of carbon and energy. This may have been the main factor underlying
      the increased ethambutol resistance of this isolate.

PMID- 30292008
TI  - Detection of radon with biosensors based on the lead(II)-induced conformational
      change of aptamer HTG and malachite green fluorescence probe.
AB  - The aim of this paper is to assemble a new biosensor for detecting the
      accumulated radon dose in the environment to achieve rapid monitor of radon.
      Based on the correlation between radon and its stable decay daughter 210Pb, a
      biosensor using the lead-induced specific aptamer HTG conformational changes, and
      the organic dye malachite green (MG) as a fluorescent probe was assembled. In
      these studies, we explored a novel, sensitive, label-free, fluorescence
      biosensing method for the detection of both radon and lead. The fluorescence
      intensity difference has a linear relationship with Pb2+ and the accumulated
      radon concentration from 6.87 * 103 Bq.h/m3 to 3.49 * 105 Bq.h/m3. The lead and
      radon detection limits of this method are 6.7 nmol/L and 2.06 * 103 Bq.h/m3,
      respectively. The student's t-test results indicated that the new method was
      reliable and stable. The detection method is sensitive, accurate, easy to
      operate, has a wide linear range and is highly selective. In the sampling and
      determination processes of radon, the radiation harm to human health can be
      effectively avoided.

PMID- 30292009
TI  - Peripheral Blood versus Bone Marrow from Unrelated Donors: Bone Marrow Allografts
      Have Improved Long-Term Overall and Graft-versus-Host Disease-Free, Relapse-Free
      Survival.
AB  - Peripheral blood (PB) and bone marrow (BM) from unrelated donors can serve as a
      graft source for hematopoietic cell transplantation (HCT). Currently, PB is most
      commonly used in roughly 80% of adult recipients. Determining the long-term
      impact of graft source on outcomes would inform this decision. Data collected by
      the Center for International Blood and Marrow Transplant Research from 5200 adult
      recipients of a first HCT from an 8/8 or 7/8 HLA antigen-matched unrelated donor
      for treatment of acute leukemia, chronic myelogenous leukemia, or myelodysplastic
      syndrome between 2001 and 2011 were analyzed to determine the impact of graft
      source on graft-versus-host disease (GVHD) relapse-free survival (GRFS), defined
      as freedom from grade III/IV acute GVHD, chronic GVHD requiring immunosuppressive
      therapy, relapse, and death, and overall survival. GRFS at 2 years was superior
      in BM recipients compared with PB recipients (16%; 95% confidence interval [CI],
      14% to 18% versus 10%; 95% CI, 8% to 11%; P <.0001) in the 8/8 HLA-matched cohort
      and 7/8 HLA-matched cohort (11%; 95% CI, 8% to 14% versus 5%; 95% CI, 4% to 7%; P
      = .001). With 8/8 HLA-matched unrelated donors, overall survival at 5 years was
      superior in recipients of BM (43%; 95% CI, 40% to 46% versus 38%; 95% CI, 36% to
      40%; P = .014). The inferior 5-year survival in the PB cohort was attributable to
      a higher frequency of deaths while in remission compared with the BM cohort. For
      recipients of 7/8 HLA-matched grafts, survival at 5 years was similar in BM
      recipients and PB recipients (32% versus 29%; P = .329). BM grafts are associated
      with improved long-term GRFS and overall survival in recipients of matched
      unrelated donor HCT and should be considered the unrelated allograft of choice,
      when available, for adults with acute leukemia, chronic myelogenous leukemia, and
      myelodysplastic syndrome.

PMID- 30292010
TI  - Patient Perspectives Regarding Allogeneic Bone Marrow Transplantation in
      Myelofibrosis.
AB  - Hematopoietic stem cell transplantation (HCT) is a curative treatment for
      patients with myelofibrosis (MF); however, many HCT-eligible patients decline
      this potentially life-saving procedure. The reasons behind this decision are not
      clear. We sought to survey patients with MF to understand their perspective on
      HCT. A 63-question survey was posted on myeloproliferative neoplasm patient
      advocacy websites. A total of 129 patients with MF responded to the survey. Among
      these patients, 49 (41%) were referred for HCT, and 41(32%) attended the
      transplantation consult. Of the patients who attended the transplantation
      consult, 24 (59%) did not plan on going on to HCT, and 16 (41%) intended to
      proceed with HCT. Reasons for the decision to not undergo transplantation
      included the desire to not be ill, desire to not spend time in the hospital, and
      concerns about overall quality of life. Specifically, concerns related to
      financial impact and the risk of graft-versus-host disease (GVHD) were expressed.
      Patients who decided to proceed with HCT felt that this would extend their
      survival and allow them to be around family for longer. This is the first survey
      to investigate patient perceptions regarding HCT for MF. Less than one-half of
      the patients were referred for HCT, and of those, less than one-half planned on
      proceeding with the transplantation, suggesting that many patients do not receive
      this life-saving procedure. Further exploration of the basis of patients'
      reluctance to proceed with HCT is warranted.

PMID- 30292011
TI  - Umbilical Cord Blood Transplantation Using Reduced-Intensity Conditioning without
      Antithymocyte Globulin in Adult Patients with Severe Aplastic Anemia.
AB  - Umbilical cord blood transplantation (UCBT) is a possible option for patients
      with aplastic anemia (AA) without a related or unrelated HLA-matched donor,
      particularly if immunosuppressive therapy (IST) has failed or transplantation is
      urgently needed. However, a higher rate of graft failure after UCBT remains a
      major problem, and the optimal conditioning regimen for stable engraftment after
      UCBT has not been established. Here we investigated 6 adult patients with AA who
      underwent UCBT using a reduced-intensity conditioning (RIC) regimen comprising
      fludarabine 125 mg/m2, cyclophosphamide 120 mg/kg, and 4 Gy of total body
      irradiation (Flu/CY/TBI4Gy) without antithymocyte globulin (ATG). Five patients
      underwent UCBT after IST failure, and 1 patient underwent UCBT as a first-line
      treatment due to a fulminant clinical finding of a neutrophil count of 0, despite
      granulocyte colony-stimulating factor administration. Regarding graft-versus-host
      disease (GVHD) prophylaxis, 2 patients received tacrolimus plus short-term
      methotrexate and 4 patients received tacrolimus plus mycophenolate mofetil, and
      all patients achieved sustained engraftment of both neutrophils and platelets, at
      a median of 17.5 days (range, 14 to 37 days) and 38.5 days (range, 31 to 86
      days), respectively, with complete donor chimerism confirmed in all patients at a
      median of 14 days (range, 14 to 32 days). Three patients developed grade II acute
      GVHD (aGVHD), but grade III/IV aGVHD was not observed, whereas 4 patients
      developed chronic GVHD involving only skin. At the time of this report, all 6
      patients were alive without the need for blood transfusion, at a median follow-up
      of 16 months (range, 12 to 131 months). Although further study is needed, our
      findings suggest that conditioning with Flu/CY/TBI4Gy without ATG might allow
      stable engraftment in UCBT for adults with AA.

PMID- 30292012
TI  - Development of aerobic granular sludge under tropical climate conditions: The key
      role of inoculum adaptation under reduced sludge washout for stable granulation.
AB  - Aerobic granular sludge (AGS) is a promising technology for wastewater treatment.
      However, the success of the process depends on the formation of stable granular
      biomass, which is associated with the microbiological aspects of the sludge and
      reactor operating conditions. In this study, the development of AGS from a poor
      nitrifying flocculent sludge obtained in a sewage treatment plant designed only
      for organic matter removal was assessed in a sequencing batch reactor (SBR) under
      tropical climate conditions (temperatures of 28 +/- 4  degrees C). The results
      showed that, despite the alternating anaerobic-aerobic conditions during the
      granules selection phase under high sludge washout rates (low settling time),
      readily biodegradable organic matter was mainly removed aerobically. The formed
      granules were unstable, exhibiting a substantial amount of filaments and pasty
      consistency. The biomass characteristics (e.g., sludge volume index, density,
      diameter and settling velocity) were negatively impacted as complete granulation
      was reached, while biomass loss and degranulation became inevitable. Poor
      nitrification and no enhanced biological phosphate removal (EBPR) were observed.
      Implementation of a new operational strategy incorporating an adaptation of the
      seed sludge under reduced washout conditions (high settling time) prior to the
      granules selection stage enabled most of the influent organics to be removed
      anaerobically. Besides allowing a feast-famine regime to be established in the
      reactor, the sludge acclimation phase favoured the development of slow-growing
      organisms and suppressed the appearance of filamentous-like structures. Fast
      settling granules with regular shape remained stable in the long-term, while high
      ammonium (>95%) and total nitrogen removal (>90%) was obtained. However, EBPR
      activity was very unstable, most likely due to the high temperatures. The
      findings of this study are important for the spreading of the AGS technology
      worldwide, especially in developing countries where the conditions are different
      in all aspects.

PMID- 30292013
TI  - Evaluation of direct and alternating current on nitrate removal using a
      continuous electrocoagulation process: Economical and environmental approaches
      through RSM.
AB  - This study aims to investigate the effects of alternating current (AC) and direct
      current (DC) for nitrate removal and its operating costs by using a continuous
      electrocoagulation (CEC) process. For this purpose, two series of 31 experiments,
      which were designed by response surface method (RSM), were carried out in both
      cases of the AC and the DC modes. In each series, the effect of selected
      parameters, namely, initial nitrate concentration, inlet flow rate, current
      density and initial pH along with their interactions on the nitrate removal
      efficiency as well as its operating costs, as responses, were investigated
      separately. According to the analysis of variance (ANOVA), there is a reasonable
      agreement between achieving results and the experimental data for both responses.
      The nitrate removal in the AC mode was slightly more efficient than that of the
      DC mode. In addition, the average operating costs of the DC mode, including the
      energy and the electrode consumption for the CEC process were achieved 54 US$/(kg
      nitrate removed); whereas this amount was calculated 29 US$/(kg nitrate removed)
      for the AC mode. Therefore, the average of the operating costs was improved more
      than 40% using the AC mode, which was mainly related to reduction of aluminum
      electrode consumption.

PMID- 30292014
TI  - The transition towards a bio-based economy: A comparative study based on social
      network analysis.
AB  - This paper focuses on the development of a bioplastics innovation niche as an
      important sector of the bio-based economy and a viable solution to promote
      sustainable long-term growth. Relying on the Strategic Niche Management
      framework, the following niche mechanisms are analysed: (1) convergence of
      expectations, (2) learning processes, and (3) networking with powerful actors in
      the sector. We conducted a comparative analysis, looking at Italy and Germany,
      two frontrunner countries in the bioplastic production who have enacted divergent
      policies in support of this sector. The comparative perspective has brought some
      interesting insights into the maturity level of the two respective niches, as
      well as into the emerging architectural properties of the underling social
      networks. Core findings show a general high level of expectations in the
      bioplastics sector in both countries, whereas key elements undermining the niche
      development refer either to the lack of policy support or to the changing and
      unstable institutional and regulatory framework. Regarding the architectural
      structure, the Italian network of actors was largely characterized by an active
      exchange of knowledge among firms, whereas the German network was characterized
      by the presence of several institutional actors actively participating in
      knowledge flows. This last result relates, in the authors' view, to the different
      policy strategies followed by national governments in the two countries: the
      German case being characterized by large public investment in R&D, whereas the
      Italian case is mostly characterized by demand side policies that effectively
      created a market for bioplastic shoppers.

PMID- 30292015
TI  - Utilizing of neodymium vanadate nanoparticles as an efficient catalyst to boost
      the photocatalytic water purification.
AB  - Neodymium Vanadate (NdVO4) nanostructures were successfully synthesized via a
      modified solid state method in the presence of ligand. These nanoparticles were
      further used as a photocatalyst. Primarily the best structural formations and
      smallest crystallite sizes of the systems were identified and optimized by
      changing the calcination time, calcination temperature and molar ratio of the
      ligand. The cationic (Methyl Violet (MV)), and anionic (Eosin Y (EY) and
      Eriochrome Black T (EBT)) dyes were used as a model to evaluate the photoactivity
      under UV-Vis irradiation. Several operational factors were examined to improve
      the photocatalytic efficiency include type of dye, type of light source, pH and
      dye concentration. As a result, the best efficiency in 5 ppm Eriochorome Black T
      at pH = 11 was achieved in the presence of 0.05 g NdVO4 nanocatalysts.

PMID- 30292016
TI  - Urban-centric resilience in search of theoretical stabilisation? A phased
      thematic and conceptual review.
AB  - Over the last decades 'resilience' has particularly arisen as an attractive
      perspective with respect to cities. As cities continue to expand, their
      susceptibility to uncertainties and new challenges, such as climate change, has
      increased, rendering 'urban resilience' an increasingly favoured concept in the
      realm of Urban Development, Planning and Management (UDPM). Despite recent
      reviews, an updated analysis of the concept is required to understand whether
      there is in fact scientific evidence to support the expansion and favouring of
      'urban resilience' in UDPM. The need to understand how the concept evolved is
      further emphasised by the need to perceive how the distinct sciences have
      contributed to its development, and which were the focuses and conceptual
      underpinnings of such evolution. Thus, the objective of this paper is to provide
      a broader review of the multidimensional concept of 'urban resilience', while
      understanding how distinct research fields have contributed to its inception and
      expansion, and how distinct conceptualisations of resilience have influenced its
      evolution. Supported by a bibliometric analysis of urban-centric publications,
      this paper highlights the recent extensive growth and expanding application of
      'urban resilience' to distinct research fields, as well as an apparent
      theoretical stabilisation of the concept, which reemphasises the idea of a three
      dimensional conceptual resilience perspective in scientific literature: (1)
      'engineering', (2) 'ecological', and (3) 'social-ecological resilience'.
      Consequently, this research emphasises that, if the related conceptual
      underpinnings are clear, 'urban resilience' can potentially serve as an
      'integrative metaphor', adapted by diverse stakeholders, to reinforce UDPM
      initiatives.

PMID- 30292017
TI  - Effects of light intensity on biomass, carbohydrate and fatty acid compositions
      of three different mixed consortia from natural ecological water bodies.
AB  - This study investigated the effect of light intensity on three various microalga
      consortia collected from natural ecological water bodies (named A, B and C)
      towards their fatty acid profiling and fractions, carbohydrate and protein
      production at different light intensities of 100, 200 and 300 MUmol m-2 s-1. The
      results indicating that increasing light intensity positively correlated with the
      lipid production than carbohydrate and protein. Irrespective to the solids (Total
      and Volatile Solid) content, lipids and carbohydrate has varied significantly.
      Consortia C showed higher productivity toward lipids, whereas consortia A and B
      accumulated more carbohydrate and protein, respectively. The microscopic images
      revealed the breakdown of cells during the increase in light intensity, in spite,
      the similar algal species were observed in all consortia experimented. Principal
      component analysis (PCA) revealed that low light intensity aid relatively in high
      protein, Total Nitrogen and Total Phosphorus, meanwhile high intensity attributed
      carbohydrates and unsaturated fatty acids (USFA) contents.

PMID- 30292018
TI  - Study of the effect mechanism of municipal solid waste gasification conditions on
      the production of H2 and CO using modelling technique.
AB  - The municipal solid waste (MSW) gasification process was numerically studied in
      the work. The effect mechanisms of particle size, temperature and gasification
      atmosphere on the production of H2 and CO were investigated in detail. The
      results demonstrated that the total volume fraction of H2 and CO dropped from
      51.7% to 49.7% with particle size increasing from 20 < d < 30 mm to 80 < d < 100
      mm under steam atmosphere. With the temperature increasing from 600  degrees C to
      1000  degrees C, the total volume fraction of H2 and CO was raised from 56.1% to
      65.8% under steam atmosphere. Five different gasifying agents: 100%CO2,
      21%O2/79%N2, 21%O2/79%H2O, 21%CO2/79%H2O, 21%O2/79%CO2 were simulated, and the
      total volume fraction of H2 and CO was 51.87%, 19.1%, 56.13%, 48.36% and 42.98%,
      respectively. In the gasification conditions considered in this work, H +
      H2O<=>OH + H2 (R84) played a key role in the yield of H2, and the yield of CO was
      significantly affected by H + CO2<=>OH + CO (R99) and H + CH2CO<=>CH3+CO (R81).

PMID- 30292019
TI  - Effectiveness of pig sludge as organic amendment of different textural class mine
      tailings with different periods of amendment-contact time.
AB  - The present study assesses the effect of tailing texture (loamy sand (LT) and
      sandy loam (ST)), dose of pig sludge (0, 50, 100 and 200 t ha-1) and amendment
      contact time (14, 28 and 42 days) on physicochemical quality of amended substrate
      using Lolium perenne var Nui as a bioindicator. The main properties of LT
      differed of ST in levels of total organic carbon (0.19 and 0.58%), in pH (4.6 and
      8.5), total Cu (202 and 1647 mg kg-1) and Zn content (31 and 137 mg kg-1). Soil
      pore water of experimental substrates was characterized for pH, electrical
      conductivity (EC) and Cu2+ ion activity (pCu2+) while ammonium nitrogen (NH4+-N),
      infiltration rate and general physicochemical characteristics were measured in
      substrates. Shoot biomass (SB), root biomass (RB) and the RB:SB ratio was
      calculated for L. perenne. The results showed there to be a significant
      interaction (p < 0.05) between tailing texture, sludge dose and amendment-contact
      time for pCu2+, infiltration rate, SB, RB, and RB: SB ratio, but not for pH, EC,
      or NH4+-N. However, sludge dose and amendment-contact time significantly affected
      all variables. By increasing dosages of pig sludge, pore water pH increased, and
      this was associated with decreases in pCu2+ and the infiltration rate. High doses
      of pig sludge (100 and 200 t ha-1) impaired growth of L. perenne irrespective of
      tailing texture and amendment-contact time, likely because of the rise of EC (up
      to 14 mS cm-1). For both tailing textures, the highest biomass was obtained after
      incorporation of 50 t ha-1 of pig sludge, with increasing values as amendment
      contact time rose. In conclusion, effective management of pig sludge for tailing
      reclamation should guarantee doses <50 t ha-1 and amendment-contact time >28
      days, irrespective of tailing texture.

PMID- 30292020
TI  - Concurrent Guillain-Barre syndrome, transverse myelitis and encephalitis post
      Zika: A case report and review of the pathogenic role of multiple arboviral
      immunity.
AB  - We review post-infectious and post-vaccination neurological syndromes involving
      peripheral and central nervous system (CNS) and report an illustrative case of
      simultaneous occurrence of Guillain-Barre syndrome (GBS), confirmed by nerve
      conduction velocities, plus MRI-demonstrated transverse myelitis (TM) and acute
      encephalitis [acute disseminated encephalomyelitis] (ADEM+GBS) affecting a 24
      year-old woman from Cucuta, Colombia, who developed acute Zika virus (ZIKV)
      infection confirmed by serum reverse transcriptase-polymerase chain reaction (RT
      PCR) and convalescent ZIKV IgG antibodies. With intensive care treatment,
      respiratory support, steroids, and intravenous immunoglobulin (IVIg), patient
      survived with residual flaccid paraparesis. She had preexisting immunity against
      Chikungunya virus (CHIKV) and Dengue virus (DENV) acquired before the arrival of
      ZIKV in Colombia. From reports in the Caribbean, Central and South America we
      review 19 cases of ZIKV-associated TM, encephalitis and ADEM occurring after a
      mean latent period of 10.5 days (range 1-96) post-infection. Although GBS and
      ADEM are usually considered post-infectious and associated with development of
      antibodies against peripheral nerve and CNS epitopes, we postulate that our case
      of ADEM+GBS is para-infectious, induced by acute ZIKV neurotropism boosted by
      active immunity against other arboviruses. Animal models of ZIKV demonstrated
      strong viral neurotropism enhanced by passive immunity with antibodies against
      arboviruses such as West Nile virus, CHIKV, or DENV. These considerations are
      relevant to prevent potential ZIKV vaccine-induced reactions involving central
      and peripheral nervous system.

PMID- 30292021
TI  - Mitochondrial DNA G15927A and G15928A variations in patients with multiple
      sclerosis.
AB  - BACKGROUND: Modern genetics has offered a fresh perspective on the pathology of
      Multiple Sclerosis (MS). As mitochondrial DNA (mtDNA) variations are held to be
      potential contributors to the complex pathobiology of MS, the present study tests
      the claim that mtDNA G15927A or G15928A variations, or both, are associated with
      MS in an Iranian population. MATERIALS AND METHODS: Following DNA extraction from
      blood samples of 100 subjects with relapsing-remitting MS, and 100 healthy
      unrelated control subjects, PCR-RFLP analyses was carried out by HpaII
      restriction enzyme reaction. Electrophoresis was then performed with 3% Agarose
      gel. As the restriction enzyme did not differentiate between two neighboring
      nucleotide positions (G15927A and G15928A), all PCR products with a variant
      allele were sequenced to determine the exact position of the variation. RESULTS:
      The MtDNA G15927A or G15928A variations were observed in 11 of all 100 cases of
      MS (11%) and in 7 of 100 healthy control subjects (7%) (P = 0.3, OR = 1.6, 95% CI
      = 0.5-5.2). Having sequenced all the PCR products with the variant allele (11
      cases and 7 controls), the mtDNA G15927A variation was found in one of the 100
      cases (1%) and 3 of 100 controls (3%) (P = 0.3, OR = 0.3, 95% CI = 0.0-4.1).
      Therefore, the mtDNA G15928A variation was present in 10 of the 100 cases (10%)
      and in 4 of 100 controls (4%) (P = 0.09, OR = 2.6, 95% CI = 0.7-12.0).
      CONCLUSION: Neither mtDNA variation, G15927A or G15928A, was associated with MS
      in the studied Iranian population. There was a non-significant association of the
      G15927A and the G15928A variations separately with MS.

PMID- 30292022
TI  - An evaluation of suicide prevention hotline results in Taiwan: Caller profiles
      and the effect on emotional distress and suicide risk.
AB  - BACKGROUND: Hotlines are among commonly available and recommended suicide
      prevention strategies in many countries, but only a few empirical studies have
      focused on people who used this service and the proximal outcomes of calls made
      to the hotlines. This study is designed to investigate the demographic
      characteristics of the Taiwan National Suicide Prevention Hotline (NSPH) callers
      and whether the NSPH service helps to alleviate the callers' emotional distress
      and suicide risk. METHODS: Descriptive statistics were used to describe the
      gender, age and county/city distribution of the 63,696 callers from 2009 to 2011.
      Three hundred telephone records of 100 acute suicidal callers, 100 suicidal
      callers, and 100 non-suicidal callers were then randomly selected for further
      investigation of the proximal changes in the callers' emotional disturbance and
      suicidality. RESULTS: Notwithstanding the suicide status of the callers,
      significant decreases in their emotional distress and suicidality could be
      detected during the course of the telephone session. Men, the elderly, and people
      living outside northern Taiwan, however, were less likely to call the NSPH. An
      unexpected yet significant finding is that people with an ongoing suicide attempt
      were less emotionally distressed than those with only suicidal thoughts.
      CONCLUSIONS: The hotline is a useful suicide preventive and crisis intervention
      service. However, further creative and consistent work is needed to make the
      service more appealing to the hard-to-reach population.

PMID- 30292023
TI  - Correlation between depression/anxiety symptom severity and quality of life in
      patients with major depressive disorder or bipolar disorder.
AB  - OBJECTIVE: To study the correlation between depression/anxiety severity and the
      quality of life (QOL) in patients with major depressive disorder (MDD) or bipolar
      disorder (BP). METHODS: Two hundred forty-three outpatients diagnosed with MDD or
      BP were used to study the relationship between depression/anxiety severity and
      QOL. Depression and anxiety symptom-severity were measured with the QIDS-16-SR
      (the 16 Item Quick Inventory of Depressive Symptomatology - Self Report), and
      Zung-SAS (Zung Self-Rating Anxiety Scale). The QOL was measured with the Q-LES-Q
      short-form (the Quality of Life, Enjoyment and Satisfaction Questionnaire).
      Correlation was assessed with regression analysis. RESULTS: The percentage of
      maximum possible scores (MPS) of Q-LES-Q was 72.1%, 70.5%, and 67.6% for euthymic
      MDD, BPI, and BPII, respectively. Increases in QIDS-16-SR total scores
      significantly correlated to decreases in Q-LES-Q total scores, with an R2 = 0.61,
      R2 = 0.52, and R2 = 0.45 for MDD, BPI, and BPII, respectively. Increases in Zung
      SAS scores also significantly correlated to decreases in Q-LES-Q total scores
      with an R2 = 0.20, R2 = 0.21, and R2 = 0.12 for MDD, BPI, and BPII. However,
      after controlling for depression severity, significant differences between Q-LES
      Q and Zung-SAS scores disappeared in MDD and BP. After controlling for anxiety
      and other clinical variables, the negative correlation between QIDS-16-SR and Q
      LES-Q scores remained significant in MDD and BP. CONCLUSIONS: In this outpatient
      sample, the MPS of Q-LES-Q in euthymic MDD and BP patients was at the lower end
      of non-psychiatric or medical community norm spectrum. Depression severity was
      the only independent variable negatively correlated to the QOL in both disorders.

PMID- 30292024
TI  - Immobilization of phenol-containing molecules on self-assembled monolayers on
      gold via surface chemistry.
AB  - Various phenol-containing molecules such as flavonoids have a wide range of
      biological effects including anticancer, antimicrobial, and anti-inflammatory
      properties, and, therefore, they have become subjects of active research for
      various medicinal and biological applications. To construct applicable materials
      incorporated with phenol-containing molecules, strategies for immobilization of
      phenol-containing molecules on solid substrates are required. Although several
      immobilization methods have been devised and reported, mostly harnessing phenol
      functionality, however, development of a general immobilization method has been
      hampered due to its complicated chemical reactions and low reaction yields on
      surfaces. Furthermore, the use of phenol as a reaction center may compromise the
      biological activity of phenol-containing molecules. Here, we describe a simple,
      fast, and reliable method for the surface immobilization of phenol-containing
      molecules by introducing chemical functional groups, carboxylic acid, thiol, and
      azide, while maintaining phenol functionality by way of the Mannich-type
      condensation reaction. We examined the chemical functionalization of naphthol,
      tyrosine, and flavanone and their immobilization to the self-assembled monolayers
      on gold via various surface chemistries: the carbodiimide coupling reaction,
      Michael addition, and the 'click' reaction. We strongly believe our method can be
      a general and practical platform for immobilization of various phenol-containing
      molecules on surfaces of various materials.

PMID- 30292025
TI  - Electrospun preparation and biological properties in vitro of polyvinyl
      alcohol/sodium alginate/nano-hydroxyapatite composite fiber membrane.
AB  - The composite fiber membrane of polyvinyl alcohol (PVA)/sodium alginate (SA)/nano
      hydroxyapatite (nHAP) was fabricated by electrospinning method. In order to
      prevent the agglomeration and precipitation of nHAP in aqueous spinning solution,
      nHAP was ultrasonically suspended in aqueous solution using SA (the component of
      composite membrane) as stabilizer. The effect of nHAP on the morphology and
      mechanical property of composite fiber membrane was investigated. The in vitro
      biological properties including hemolysis, cytotoxicity, cell adhereing and
      proliferation of composite fiber membrane were evaluated. Results show that SA
      stabilized nHAP (SA-nHAP) suspension (1.67-10.02 mg/mL) can be obtained with
      SA/nHAP mass ratio of 1:33.4 for preparing homogeneous spinning solution. The
      electrospun membranes with PVA/SA/nHAP mass ratio of 9.33:(0.67-0.69):(0-0.668)
      show good fiber morphology, homogeneous incorporation and distribution of nHAP in
      fibers, and the content of SA-nHAP (6.25 wt%) in membrane is significantly
      increased compared to that of untreated nHAP (3.23 wt%). The incorporation of SA
      nHAP of 1.64 wt.% significantly improves the tensile strength of PVA/SA/nHAP
      fiber membrane with about 45% enhancement. The hemolysis and cytotoxicity tests
      show that the composite fiber membrane has good biocompatibility. Moreover, cells
      can be seeded and proliferate well on composite fiber membrane. Therefore, the
      obtained PVA/SA/nHAP composite fiber membrane has the potential use as a tissue
      regeneration material.

PMID- 30292026
TI  - Fractionated Radiotherapy Is Associated with Lower Rates of Treatment-Related
      Edema than Stereotactic Radiosurgery in Magnetic Resonance Imaging-Defined
      Meningiomas.
AB  - OBJECTIVE: Both stereotactic radiosurgery (SRS) and fractionated radiation
      therapy (FRT) techniques are used for treatment of intracranial meningiomas with
      excellent local control (LC) rates. Although SRS techniques are convenient,
      toxicity including treatment-related edema can significantly impact patient
      quality of life. The long-term clinical outcomes of patients with magnetic
      resonance imaging (MRI)-defined meningiomas treated with radiation therapy (RT)
      alone are reported. METHODS: The charts of 211 patients with meningiomas
      diagnosed by contrast-enhanced MRI treated with either SRS or FRT between 1991
      and 2012 at a single institution were reviewed. Actuarial rates for LC and
      development of treatment-related radiographic edema (TRE) were determined by the
      Kaplan-Meier method. RESULTS: There were 211 patients who received radiation
      therapy for 223 lesions. Median follow-up was 5.7 years. Eleven patients
      experienced a local failure; of these, 2 were ultimately found to have
      pathologically proven metastatic carcinoma. Two- and 5-year LC was 97.8% and
      94.6%, respectively, with no significant difference based on modality of therapy.
      Actuarial rate for development of TRE at 1 and 2 years was 30.1% and 34.6% for
      the SRS group and 1.6% and 2.5% for the FRT group, respectively (P < 0.001).
      CONCLUSIONS: RT alone using a limited margin is an effective treatment option for
      MRI-defined meningiomas and should be considered even without biopsy if surgery
      will present significant morbidity. Although LC with SRS versus FRT was
      comparable, FRT was associated with a significantly decreased risk of TRE.

PMID- 30292027
TI  - The Ongoing Revolution in Thrombectomy: Expanding Inclusion Criteria to Larger
      Cores.

PMID- 30292028
TI  - Combined Lateral Transpsoas Anterior Column Realignment with Pedicle Subtraction
      Osteotomy to Treat Severe Sagittal Plane Deformity: Cadaveric Feasibility Study
      and Early Clinical Experience.
AB  - BACKGROUND: Traditional open approaches to correct lumbar spine deformities
      include 3-column osteotomies, such as a pedicle subtraction osteotomy (PSO).
      Minimally invasive surgical (MIS) techniques have been developed for lateral
      transpsoas anterior column realignment (ACR). These 2 techniques have not
      previously been combined. Our objective was to investigate the cadaveric
      feasibility of a combined hybrid MIS ACR-PSO technique for deformity correction
      and to review early clinical experience. METHODS: The feasibility of the combined
      ACR-PSO technique was evaluated in 4 fresh cadaveric specimens. The operative
      experience, complications, and early clinical outcomes in patients treated with
      the combined approach to correct global sagittal imbalance were reviewed.
      RESULTS: In the cadaveric study, the combined ACR-PSO resulted in a mean 46.0
      degrees  increase in lordosis (P < 0.001). Nine patients treated with ACR-PSO
      were evaluated (mean age, 65.2 years; 33.3% female). Most patients (6/9; 66.7%)
      underwent ACR at L1/2 or L3/4; 8 (88.8%) had PSO at L3 or L4. On average, 10.6 +/
      3.8 levels were fused. Significant decreases in mean pelvic tilt (P = 0.01),
      spinopelvic mismatch (P < 0.001), and T1 spinopelvic inclination (P = 0.03) were
      observed postoperatively; mean lumbar lordosis (P = 0.007), intradiscal angle (P
      = 0.001), and thoracic kyphosis (P = 0.04) significantly increased. The overall
      complication rate was 55.6% (5/9). CONCLUSIONS: Our early experience suggests
      that a combined ACR-PSO with posterior fixation allows for significant correction
      of segmental lordosis and global imbalance. This combined approach may maximize
      results attainable with hybrid MIS-open surgical techniques and represents a
      complementary option to PSO and other posterior approaches.

PMID- 30292029
TI  - Augmenting Occlusion Outcomes Through Pipeline with Adjunctive Coiling.

PMID- 30292030
TI  - Lateral Lumbar Interbody Fusion Revisited: Complication Avoidance and Outcomes
      with the Mini-Open Approach.
AB  - OBJECTIVE: To discuss lessons learned from an initial lateral lumbar interbody
      fusion (LLIF) experience with a focus on evolving surgical technique,
      complication avoidance, and new motor and sensory outcomes after implementation
      of a modified surgical approach. METHODS: A retrospective analysis of a
      prospectively collected series of all patients undergoing LLIF by the senior
      author (A.D.L.) from January 2010 to January 2018 after implementation of a
      modified surgical mini-open technique, compared with previously reported
      institutional results with the originally recommended percutaneous technique.
      LLIF-specific complications examined included groin/thigh sensory dysfunction,
      flank bulge/pseudohernia, psoas-pattern weakness, and femoral nerve injury.
      RESULTS: The incidence (19%, n = 98 patients) of groin/thigh sensory dysfunction
      in our cohort was significantly lower than that of the historical control (60%, n
      = 59) (P < 0.0001). The incidence of abdominal flank bulge/pseudohernia (2.0%, n
      = 98 patients) in our cohort was improved but not significantly lower than that
      of the historical control (4.2%, n = 118) (P = 0.36). The incidence of psoas
      pattern weakness (3.1%, n = 98) in our cohort was significantly lower than that
      of the historical control (23.7%, n = 59) (P = 0.0001). The incidence of femoral
      nerve injury (0%, n = 98 patients) in our cohort was improved but was not
      significantly lower than that of the historical control (1.7%, n = 118) (P =
      0.20). CONCLUSIONS: The adoption of an exclusive mini-open muscle-splitting
      approach with first-look inspection of the lumbosacral plexus nerve elements may
      improve motor and sensory outcomes in general and the incidence of postoperative
      groin/thigh sensory dysfunction and psoas-pattern weakness in particular.

PMID- 30292031
TI  - Comparison of supraorbital and pterional keyhole approach for clipping cerebral
      middle artery aneurysm: A Chinese population-based Study.

PMID- 30292032
TI  - Cerebrovascular Surgery in Iran: Present Challenges and Future Directives.

PMID- 30292033
TI  - Intracranial Migration of a Broken Rod after Orbitocranial Injury in an Adult.
AB  - BACKGROUND: Craniocerebral injuries due to the induction of sharp objects are
      relatively rare and are nearly always observed in the pediatric rather than the
      adult population. Orbitocranial injuries involving a piece of smooth steel rod
      are an extremely rare incident and to our knowledge have yet to be reported in
      previous literary publications. When this particular category of injury does
      occur the invading intracranial foreign body usually remains lodged within its
      entry position. This is most often near the entry point and within the frontal
      lobe after penetrating the orbit. Migration of the penetrating objects far from
      the initial entry point is quite rare and has been historically confined to low
      velocity bullet wounds. CASE DESCRIPTION: An adult male who was injured on the
      right eyelid by a section of steel rod is presented. The rod had entered the
      cranium through the right orbital roof and was lodged within the corresponding
      right frontal lobe. An initial plain radiograph showed that the rod was within
      the right frontal lobe. However, brain CT angiography performed during the 2nd
      day of admission demonstrated displacement of the rod to the left hemisphere.
      This finding was clearly demonstrated through subsequent imaging. As a result of
      the migration, the rod could be distracted fairly easily via a left parasagittal
      and interhemispheric approach. Postoperatively, the patient made full recovery.
      CONCLUSION: Migration of traumatically introduced intracranial foreign bodies far
      from their initial entry places should be suspected in objects possessing a
      sufficient weight and a smooth surface. This means that a correct assessment of
      the final position of such objects is necessary before attempting surgery even
      while the patient is on the operating table.

PMID- 30292034
TI  - Determining the Optimal Shape-Related Indicator on Noncontrast Computed
      Tomography for Predicting Hematoma Expansion in Spontaneous Intracerebral
      Hemorrhage.
AB  - OBJECTIVE: Among several novel predictors on noncontrast computed tomography (CT)
      for hematoma expansion in spontaneous intracerebral hemorrhage (sICH), shape
      irregularity grade, satellite sign, and island sign are all related to irregular
      shape of hematoma. This study is aimed to compare the accuracy of these imaging
      markers for predicting hematoma expansion in the same cohort of sICH patients.
      METHODS: This retrospective study enrolled sICH patients who underwent diagnostic
      computed tomography (CT) scans within 6 hours after onset and another follow-up
      CT scan within 24 hours after initial CT scan. Shape irregularity grade,
      satellite sign, and island sign were assessed according to the definitions in
      previous studies. The accuracy of these imaging indicators for predicting
      hematoma expansion was analyzed using receiver operator analysis. RESULTS:
      Finally, a total of 196 patients were included. Shape irregularity grade >=3 was
      found in 87 (44.39%) patients, satellite sign was identified in 76 (38.78%)
      patients, and island sign was shown in only 41 (20.92%) patients. Only island
      sign remained an independent predictor for hematoma expansion in multivariate
      logistic regression. The sensitivity values of shape irregularity grade >=3,
      satellite sign, and island sign were 0.52, 0.63, and 0.48, respectively. By
      contrast, the specificity values of these 3 predictors were 0.58, 0.69, and 0.85,
      respectively. Shape irregularity grade >=3 had the smallest area under the curve
      (0.597), and island sign had the largest (0.676). CONCLUSIONS: Island sign seems
      to be the optimal shape-related predictor for hematoma expansion in sICH patients
      and could be included in the future predictive model for hematoma expansion.

PMID- 30292035
TI  - Central retinal artery thromboembolism without ophthalmic artery occlusion during
      stent-assisted coil embolization of an ophthalmic artery aneurysm.
AB  - BACKGROUND: Recent reports have described that endovascular treatment of coil
      embolization of ophthalmic artery (OphA) aneurysms has a relative risk of visual
      disruption caused by thromboembolic infarction of the central retinal artery
      (CRA), especially the OphA when it originates within the body of the aneurysm.
      Patent microthrombus in the OphA might also cause retinal infarction that affects
      visual acuity. We describe stent-assisted coil embolization of an OphA aneurysm
      complicated with a severe visual disturbance although normal flow was
      scrupulously maintained in the OphA during the procedure. The visual disturbance
      was recovered by early treatment. CASE DESCRIPTION: A 40-year-old woman who
      presented with an intracranial aneurysm arising from the right OphA underwent
      stent-assisted coil embolization under general anesthesia. Although the area
      around the origin of the OphA was intentionally avoided and anterograde flow in
      the OphA was monitored by repeated angiography during this procedure, sight in
      the right eye was lost immediately thereafter. The immediate application of
      ocular massage and intra-arterial fibrinolysis improved vision in the right eye
      to essentially normal status after discharge. CONCLUSIONS: Despite good
      anterograde flow in the OphA during aneurysm embolization, the procedural risk of
      a visual disturbance due to thromboembolic complications of CRA occlusion cannot
      be avoided. Anterograde flow in the OphA and retinochoroidal blush should be
      monitored by repeated angiography during coil embolization to prevent vision
      loss. Should vision be lost, a rapid response including ocular massage and intra
      arterial fibrinolysis is required for recovery.

PMID- 30292036
TI  - Hemiparesis without responsible hematomas in patients with subarachnoid
      hemorrhage undergoing early aneurysmal repair.
AB  - OBJECTIVE: The presence of hemiparesis on arrival in patients with subarachnoid
      hemorrhage (SAH) is presumed to affect their prognosis, and intracranial
      hematomas with a mass effect responsible for the hemiparesis are frequently
      observed in these patients. The purpose of this study was to clarify the
      characteristics and outcomes of patients who presented with hemiparesis on
      arrival and showed no responsible hematomas (hemiparesis w/o hematoma) having a
      mass effect on computed tomography. METHODS: Consecutive SAH patients treated
      with surgery for ruptured cerebral aneurysms within 5 days of onset between 2003
      and 2015 were retrospectively reviewed. RESULTS: Hemiparesis w/o hematoma was
      present in 25 of 858 surgically treated patients (2.9%). Internal carotid artery
      (ICA) aneurysms were significantly more common in patients showing hemiparesis
      w/o hematoma than in the other patients (p<0.05). In 19 of 21 surviving patients
      (90.5%) with hemiparesis w/o hematoma on arrival, the hemiparesis improved at
      discharge. Favorable outcomes were achieved in 16 of 25 patients showing
      hemiparesis w/o hematoma (64%) and in 13 of 59 patients showing hemiparesis with
      hematomas (22.0%), and the difference was significant (p<0.05). CONCLUSIONS: The
      hemiparesis could be expected to improve in SAH patients with hemiparesis w/o
      hematoma, and such patients appear to have a better prognosis than those having
      SAH with hemiparesis and responsible hematomas. A possible major mechanism of
      hemiparesis w/o hematoma based on the characteristics identified was a
      combination of transient ipsilateral hemispheric functional failure caused by the
      impact of aneurysmal rupture and transient ischemia of the perforators
      originating from the ICA.

PMID- 30292037
TI  - Significance and Prognostic Value of The Coagulation Profile in Patients with
      Glioblastoma: Implications for Personalized Therapy.
AB  - BACKGROUND: Coagulation is an important aspect of the vascular microenvironment
      in which brain tumors evolve. Patients with tumor often show aberrant coagulation
      and fibrinolysis activation. In particular, glioblastoma (GBM), the most
      aggressive primary brain tumor, is associated with a state of hypercoagulability,
      and venous thromboembolism is a common complication of this cancer and its
      treatment. Our study aims to investigate the clinical and prognostic significance
      of routine laboratory tests to assess the coagulative state of patients with
      brain tumors, to identify potential new prognostic factors and targets for
      personalized therapy. METHODS: Blood samples were collected from patients with
      GBM (n = 58) and patients with meningioma (MNG, n = 22), before any treatment.
      The parameters analyzed were prothrombin time (PT), activated partial
      thromboplastin time (aPTT), D dimer (DD), fibrinogen, von Willebrand factor
      (VWF), leukocyte count, and hemoglobin levels. RESULTS: Plasma levels of PT and
      aPTT were significantly reduced in GBMs compared with MNGs (P < 0.05), whereas
      DD, VWF:Ag levels, and leukocyte count were significantly higher in GBMs than in
      MNGs (P < 0.01). Furthermore, we observed that patients with GBM with reduced PT
      and aPTT and high levels of DD and VWF, defined as hypercoagulable patients,
      showed reduced overall survival (P < 0.05) compared with nonhypercoagulable
      patients. CONCLUSIONS: Our data support the assumption that patients with GBM
      show a plasma hypercoagulable profile and that coagulation profile is related to
      adverse outcome in patients with GBM. If confirmed, hypercoagulability could play
      an important role as a prognostic factor of the disease and in the decision of an
      antithrombotic prophylaxis.

PMID- 30292038
TI  - Pituitary Apoplexy following Endoscopic Retrograde Cholangiopancreatography.
AB  - BACKGROUND: Pituitary apoplexy is an uncommon neurosurgical emergency which may
      be the initial presentation of undiagnosed pituitary adenomas. Though the exact
      pathogenesis is unclear, there appears to be an association between pituitary
      apoplexy and medical interventions which disturb the blood supply and venous
      drainage of the abnormal sellar region. We present the first case of pituitary
      apoplexy occurring after an endoscopic retrograde cholangiopancreatography
      (ERCP). CASE DESCRIPTION: A 43-year-old male who was several hours status post
      ERCP presented with severe headache, bilateral ptosis and multi-directional
      ophthalmoplegia. Computed tomography (CT) scan and magnetic resonance imaging
      (MRI) of the brain revealed a hemorrhagic and necrotic sellar mass with
      suprasellar extension compressing the optic chiasm and bilateral extension
      displacing the cavernous carotid arteries laterally. The patient underwent
      emergent endoscopic transsphenoidal resection of the underlying pituitary tumor
      apoplexy with eventual resolution of his cranial nerve palsies. CONCLUSIONS:
      Although pituitary apoplexy has been recognized as a sequela of surgical and
      laparoscopic procedures, it should also be considered in less invasive
      gastrointestinal (GI) procedures which may alter the intraabdominal pressures,
      such as ERCP. Early detection of this unusual complication allows for rapid
      diagnosis and timely surgical intervention in select cases to prevent
      debilitating cranial nerve palsies, preserve visual function, and retain normal
      pituitary function.

PMID- 30292039
TI  - Minimally Invasive Evacuation of Spontaneous Cerebellar Intracerebral Hemorrhage.
AB  - OBJECTIVE: Spontaneous cerebellar intracerebral hemorrhage (scICH) constitutes
      ~10% of all cases of spontaneous ICH, with a mortality of 20%-50%. Suboccipital
      craniectomy (SOC) is commonly performed for scICH causing brainstem compression
      or hydrocephalus. However, SOC requires long anesthesia times and results in a
      high complication rate. We present a series of patients who minimally invasive
      scICH evacuation as an alternative to traditional SOC. METHODS: We
      retrospectively reviewed the operative records for patients presenting to a
      single center from January 1, 2009 to March 1, 2017. All patients who had
      undergone evacuation of scICH were included in the present study. Clinical and
      radiographic variables were collected, including admission and postoperative
      Glasgow coma scale (GCS) scores, preoperative and postoperative hematoma volumes,
      and modified Rankin scale (mRS) scores at long-term follow-up. RESULTS: We
      identified 10 patients who had presented with scICH requiring surgery. All scICH
      evacuations were performed through a minicraniectomy positioned in the
      suboccipital area as close to the hematoma as possible. The mean patient age was
      64.1 years. The mean presenting GCS score was 8.6, the mean initial hematoma
      volume was 25.4 mL, the mean procedure time was 57 minutes, and the mean
      postoperative hematoma volume was 2.8 mL. The mortality rate was 10% and mean
      long-term follow-up mRS score was 2. CONCLUSIONS: Minimally invasive scICH
      hematoma evacuation is a feasible alternative to SOC with numerous advantages
      that could lead to improved radiographic and clinical results.

PMID- 30292040
TI  - Subtotal Resection of Cervical Dumbbell Schwannomas: Radiographic Predictors for
      Surgical Considerations.
AB  - OBJECTIVE: Currently, radiologic predictors for the resectability of cervical
      dumbbell schwannomas remain unknown. To identify radiologic predictors for
      resectability, we retrospectively reviewed data from 72 patients. METHODS: From
      January 1995 to June 2017, 72 patients who underwent surgical treatment for
      cervical dumbbell schwannomas were enrolled. We focused on the relationship
      between preoperative magnetic resonance imaging (MRI) features and the extent of
      tumor removal. The MRI features evaluated were tumor size, tumor level, Eden
      classification, degree of vertebral artery (VA) involvement, and signal intensity
      (SI) on T2-weighted images (WIs). RESULTS: Among the 72 patients, gross total
      resection (GTR) and subtotal resection (STR) were achieved in 37 (51.4%) and 35
      (48.6%) patients, respectively. Mean maximal tumor size (P = 0.011), mean size of
      foraminal and extraforaminal portion (P = 0.017), tumor level (P < 0.001), VA
      involvement (P < 0.001), and SI on T2-WIs (P = 0.006) were significantly
      different between the GTR and STR groups. Univariate analyses demonstrated that
      maximal tumor size (odds ratio [OR]: 0.93, P = 0.012), high cervical level (OR:
      11.37, P < 0.001), pushed VA (OR: 0.11, P = 0.002), encased VA (OR: 0.02, P <
      0.001), and hyper-SI on T2-WIs (OR: 12.46, P = 0.020) were significant predictors
      for GTR. In the multivariate analysis, only high cervical level (OR: 5.48, P =
      0.033) and encased VA (OR: 0.07, P = 0.014) were significant predictors for GTR.
      CONCLUSIONS: The resectability of cervical dumbbell schwannomas may be predicted
      by MRI features, including tumor size, tumor level, and degree of VA involvement.

PMID- 30292041
TI  - Evaluation of Prognosis in Patients with Severe Traumatic Brain Injury Using
      Resting-State Functional Magnetic Resonance Imaging.
AB  - BACKGROUND: We investigate the change of the default mode network (DMN) by using
      amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC)
      methods in acute phase patients after severe traumatic brain injury (sTBI) and
      correlate these changes with prognosis. METHODS: Twenty-one patients with sTBI
      were included. Twenty-one healthy sex-, age-, and education-matched control
      subjects were recruited for the control group. Of the 21 patients with sTBI, 12
      patients regained consciousness (Glasgow Outcome Scale [GOS] score >2) and 9
      patients remained unconscious (GOS score <2). FC and ALFF values were measured in
      the DMN and compared between the groups. We further assessed and compared the FC
      and ALFF values in both groups. RESULTS: Patients with sTBI showed significantly
      decreased FC and ALFF values in the DMN. However, patients with a better
      prognosis showed a significant increase in FC and ALFF values in the DMN. The
      conscious subgroup showed significantly enhanced FC in the medial superior
      frontal gyrus, left temporal gyrus, anterior cingulate gyrus, precuneus,
      posterior cingulate gyrus, and parietal cortex compared with the coma subgroup.
      Increased ALFF values in the right frontal gyrus, right temporal gyrus, and right
      inferior parietal gyrus were significant in the conscious subgroup compared with
      the coma subgroup. CONCLUSIONS: Increases in FC and ALFF values in the DMN are
      related to better prognosis in patients with sTBI.

PMID- 30292043
TI  - Present Role of Surgery for Brain Metastases.

PMID- 30292042
TI  - Taming the Opioid Epidemic: The National Institutes of Health HEAL Initiative.

PMID- 30292044
TI  - Elucidating the effects of different photoanode materials on electricity
      generation and dye degradation in a sustainable hybrid system of photocatalytic
      fuel cell and peroxi-coagulation process.
AB  - The hybrid system of photocatalytic fuel cell - peroxi-coagulation (PFC-PC) is a
      sustainable and green technology to degrade organic pollutants and generate
      electricity simultaneously. In this study, three different types of
      photocatalysts: TiO2, ZnO and alpha-Fe2O3 were immobilized respectively on carbon
      cloth (CC), and applied as photoanodes in the photocatalytic fuel cell of this
      hybrid system. Photocatalytic fuel cell was employed to drive a peroxi
      coagulation process by generating the external voltage accompanying with
      degrading organic pollutants under UV light irradiation. The degradation
      efficiency of Amaranth dye and power output in the hybrid system of PFC-PC were
      evaluated by applying different photoanode materials fabricated in this study. In
      addition, the effect of light on the photocurrent of three different photoanode
      materials was investigated. In the absence of light, the reduction of
      photocurrent percentage was found to be 69.7%, 17.3% and 93.2% in TiO2/CC, ZnO/CC
      and alpha-Fe2O3/CC photoanodes, respectively. A maximum power density (1.17 mWcm
      2) and degradation of dye (93.8%) at PFC reactor were achieved by using ZnO/CC as
      photoanode. However, the different photoanode materials at PFC showed
      insignificant difference in dye degradation trend in the PC reactor. Meanwhile,
      the degradation trend of Amaranth at PFC reactor was influenced by the
      recombination rate, electron mobility and band gap energy of photocatalyst among
      different photoanode materials.

PMID- 30292045
TI  - A comparison study of in-situ coagulation and magnetic ion exchange (MIEX) as pre
      treatments for ultrafiltration: Evaluating effectiveness of organic matters
      removals and fouling mitigation.
AB  - This work was designed to compare the effectiveness of in-situ coagulation and
      MIEX as pre-treatments prior to ultrafiltration (UF) to improve organic matter
      (OM) removal and mitigate membrane fouling. Three kinds of OMs, i.e. salicylic
      acid (SA), humic acid (HA) and bovine serum albumin (BSA) were employed. The
      experimental results show that coagulation-UF led to most effective removal of HA
      (almost 90%), while the SA was uncoagulated and least removable, with the
      rejection rate of about 55%. Conversely, MIEX present superior ability for
      removing SA, contributing to additional efficiency of 71.95-77.21% than UF alone.
      Proper dosage of Al-based coagulants could alleviate flux loss, especially in the
      cases of HA and BSA. Increasing coagulant dose resulted in continuous decrement
      of irreversible resistance (Rir), which dominated the membrane fouling
      development by the SA water. For HA and BSA waters, alternatively, variations of
      Rr determined the flux declines. Floc compact degree was the decisive factor for
      Rr for coagulated SA; while for HA and BSA, Rr was most related to the floc size
      and foulant-foulant interaction. MIEX was most effective for alleviating flux
      loss when treating the hydrophilic SA with small molecules and for all the cases,
      MIEX exerted little influence on the Rr values.

PMID- 30292046
TI  - Efficient degradation of Orange G with persulfate activated by recyclable FeMoO4.
AB  - In this study, FeMoO4 was applied to activate persulfate (PS, S2O82-) for azo dye
      Orange G (OG) degradation. The catalyst was characterized by X-ray diffraction
      (XRD), scanning electron microscope (SEM), transmission electron microscope
      (TEM), X-ray photoelectron spectroscopy (XPS) and nitrogen adsorption-desorption
      isotherms. FeMoO4 showed excellent efficiency in activating PS for OG removal.
      More than 95% could be removed after 40 min under reaction conditions of 4 mM PS,
      0.3 g L-1 FeMoO4 and 0.2 mM OG. The effect of different parameters (PS doses,
      FeMoO4 doses and pH) were evaluated. The results showed that acid condition
      provided higher efficiency and overdosing FeMoO4 and PS presented a scavenging
      effect. Major intermediates were identified and possible degradation pathway was
      proposed. Recycle tests presented that FeMoO4 had excellent recyclable stability
      in activating PS for OG removal. Sulfate radicals and hydroxyl radicals all
      occurred in the oxidation reactions and the former came first. The oxidation
      reaction was involved in the translation of Fe2+/Fe3+ occurred on the surface
      layer. This study revealed that the FeMoO4/PS system is a very promising method
      for degrading organic contaminants in the environment.

PMID- 30292047
TI  - Exposure to triclosan changes the expression of microRNA in male juvenile
      zebrafish (Danio rerio).
AB  - Triclosan (TCS) is a broad-spectrum antibacterial agent which is widely used in
      various personal care products and cosmetics. It has been found that TCS affects
      endocrine, immune, nervous, reproductive, and developmental system. Although
      microRNAs (miRNAs) act a pivotal part in lots of metabolic activities, whether
      and how they are related to the process of TCS-induced toxicity is unknown. In
      the present study, TCS induced changes in miRNAs and target gene expression in
      male zebrafish (Danio rerio) brain, and the potential mechanism was studied. Male
      juvenile zebrafish were exposed to 0 and 68 MUg/L TCS for 42 d. miRNA was
      isolated from the brain pool of the zebrafish and the expression profiles of 255
      known zebrafish miRNAs were analysed by using Affymetrix miRNA 4.0 microarrays.
      Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assay the
      expression of 5 differentially expressed miRNAs in the microarray data and some
      related-genes in brains. The GO term analysis revealed that miRNAs significantly
      affected by TCS exposure were mainly involved in translation, transcription, DNA
      templated, protein transport, and motor neuron axon guidance biological process.
      Pathway analysis showed that target genes of 5 differentially expressed miRNAs
      prominently participate in basal transcription factors, purine metabolism, and
      ribosome biogenesis in eukaryotes. In addition, key genes in purine metabolism
      pathway and oxidative stress related-genes were significantly changed. These
      findings offer novel insight into the mechanisms of epigenetic regulation in TCS
      induced toxicity in male zebrafish, and distinguish novel miRNA biomarkers for
      exposure to TCS.

PMID- 30292048
TI  - Bioremediation of soils contaminated by PAHs: Mutagenicity as a tool to validate
      environmental quality.
AB  - Bioremediation can be used as one of the decontamination techniques for areas
      contamined by polycyclic aromatic hydrocarbons (PAHs). However the effective
      biodegradation of these compounds must take into account the possible toxic and
      mutagenic effects that might persist. In this study the mutagenic potential of
      soil samples from an area contaminated by wood preservatives was evaluated. The
      area had already been submitted to a simulated bioremediation process in a
      microcosm, using two different inoculums (1 and 2), and comparing them to the
      decay of PAHs. Organic extracts were prepared before and after bioremediation,
      where the 16 PAHs considered a priority by USEPA were analyzed and tested using
      the Salmonella/microsome assay. The extracts were analyzed in strains TA98, TA97a
      and TA100 (+S9mix/-S9mix), YG1041 and YG1042. Considering Inoculum 1 only as
      bioaugmented and Inoculum 2 also stimulated and enriched, the concentrations of
      PAHs and mutagenic effect were different. The former identified a greater
      reduction of mutagenesis and a smaller decrease of PAHs while the latter showed
      greater mutagenic power even associated with the greatest reduction of PAHS. The
      possible generation of degradation byproducts with high mutagenic power after a
      partial biodegradation process can be considered. In strains YG1041 and YG 1042
      the mutagenesis values before bioremediation were 747 and 567 rev/g soil,
      respectively. Although the efficiency of bioremediation was observed, the
      associated damage indicates that the analysis of contaminants and their
      relationship with mutagenic effects are a fundamental stage for the effective
      evaluation of the risks and efficiency of bioremediation processes.

PMID- 30292049
TI  - Combined photoelectrocatalytic microbial fuel cell (PEC-MFC) degradation of
      refractory organic pollutants and in-situ electricity utilization.
AB  - A new photoelectrocatalytic (PEC) and microbial fuel cell (MFC) process was
      developed and applied to simultaneously remove refractory organic pollutants
      (i.e., phenol and aniline) from wastewater while recovering energy for in-situ
      utilization. The current generated by the MFC process was applied to drive the
      PEC reaction. Compared with single PEC or MFC processes, the PEC-MFC combined
      process showed higher pollutant and chemical oxygen demand (COD) removal
      capacities and electricity production. Over 95% of the phenol or aniline was
      removed by these process, even at high initial concentrations. The COD removal
      efficiencies for phenol and aniline were ca. 96% (from 700 to 29 mg L-1) and 70%
      (from 165 to 49 mg L-1), respectively. Although the PEC process showed a limited
      contribution to phenol and aniline removals (16.5% and 43%, respectively), the
      utilization of PEC-treated phenol or aniline streams resulted in a MFC with
      higher voltage output, higher coulombic efficiency, maximal volumetric power
      density, and lower internal resistance as compared to untreated water. High
      performance liquid chromatography coupled with mass spectrometry measurements
      revealed quinones/hydroquinones and low molecular weight organic acids to be
      produced as intermediates after the PEC process, which could improve the
      production of electricity in the MFC.

PMID- 30292050
TI  - Investigation of toxicological effects of amorphous silica nanostructures with
      amine-functionalized surfaces on Vero cells.
AB  - Amorphous silica (SiO2) nanostructures are described in the literature as having
      low toxicity and are widely used in many industrial products. However, surface
      modifications, such as amine-functionalization, can result in increased
      cytotoxicity. In this study, amorphous SiO2 nanostructures (SiO2 NS) were
      synthesized and amine-functionalized with two different amine molecules: primary
      (SiO2 NS@1) and tri-amine (SiO2 NS@3). The materials were characterized by
      transmission electron microscopy (TEM), zeta potential (ZP), effective diameter
      (ED) and surface area measurements, X-ray diffraction (XRD) and Fourier transform
      infrared spectroscopy (FTIR). The toxicity of the three SiO2 NS samples toward
      Vero cells was evaluated. According to the methyl thiazolyl tetrazolium (MTT)
      assay, the IC50,24h was 1.477 +/- 0.12 g L-1 for SiO2 NS, 0.254 +/- 0.07 g L-1
      for SiO2 NS@1 and 0.117 +/- 0.05 g L-1 for SiO2 NS@3. The order of cytotoxicity
      was SiO2 NS@3 > SiO2 NS@1 " SiO2 NS. There was an increase in malondialdehyde
      (MDA) levels and ROS productions in the cells exposed to all three materials.
      Also, TEM images showed damage on the mitochondria and rough endoplasmic
      reticulum.

PMID- 30292051
TI  - Interactions between microplastics and phthalate esters as affected by
      microplastics characteristics and solution chemistry.
AB  - Microplastics have become a major concern in recent years as they can be
      recognized as the transport vectors for pollutants in environment. In this study,
      the sorption behavior of two phthalate esters (PAEs), including diethyl phthalate
      (DEP) and dibutyl phthalate (DBP), onto three types of microplastics (PVC:
      polyvinyl chloride, PE: polyethylene, and PS: polystyrene) was investigated. The
      sorption isotherms of both DEP and DBP on microplastics were highly linear,
      suggesting that the partition was the main sorption mechanism. The Kd values of
      DBP were much higher than those of DEP, demonstrating that hydrophobic
      interaction governed the partition mechanism. Sorption of the two PAEs on the
      three microplastics followed the order of PS > PE > PVC, indicating that chemical
      properties of microplastics played an important roles in their sorption
      behaviors. Solution pH and natural organic matter had no significant impact on
      PAEs sorption by microplastics. However, the presence of NaCl and CaCl2 enhanced
      the sorption of both DEP and DBP because of the salting-out effect. The findings
      of the present study may have significant implications for the fate and transport
      assessment of both PAEs and microplastics.

PMID- 30292052
TI  - Rotating packed bed as a novel disinfection contactor for the inactivation of E.
      coli by ozone.
AB  - The intensification of mass transfer and mixing in ozone-based disinfection
      processes is very important in order to achieve a certain disinfection effect at
      a reasonable cost. This study employed rotating packed bed (RPB), an efficient
      process intensification device, as an ozone-disinfection contactor, and its
      performance on disinfection and mass transfer was evaluated by the inactivation
      of Escherichia coli (E. coli) and mass transfer coefficient (kLa). The ozone
      exposure (Ct value) and the log inactivation of E. coli in the RPB reached 0.0008
      0.0014 min mg L-1 and 6.8-7.3 in phosphate buffered saline buffer, respectively.
      And the kLa in RPB rose from 0.030 to 0.186 s-1 with the increase of liquid flow
      rate from 10 to 60 L h-1. The increase of rotation speed of the RPB enhanced the
      log inactivation and kLa simultaneously. It was also noted that a higher gaseous
      ozone concentration at the identical applied ozone dosage is favorable for the
      inactivation of E. coli. The calculation of Hatta number indicated that the
      inactivation of E. coli in RPB is a diffusion-controlled process for which RPB is
      well suited. Compared to the conventional bubble reactor, the achievement of high
      disinfection efficacy at a low Ct value in RPB revealed that RPB is an efficient
      ozone disinfection contactor for the inactivation of microorganisms in water.

PMID- 30292053
TI  - Myocardial infarction after epilepsy onset: A population-based retrospective
      cohort study.
AB  - INTRODUCTION: Cardiovascular comorbidities of epilepsy such as hypertension,
      hyperlipidemia, and diabetes are associated with myocardial infarction (MI).
      Little data on the development of subsequent cardiovascular disease (CVD) in
      persons with epilepsy (PWE) are available, with inconsistent findings regarding
      the association between epilepsy and subsequent MI. A higher risk of MI among
      adults (without prior MI) following epilepsy diagnosis compared with that among
      controls was hypothesized. METHODS: This retrospective cohort study used
      statewide hospital and emergency department (ED) encounter data from 2000-2013
      for South Carolina residents aged >18 years without prior MI at the onset of
      epilepsy, or the first encounter for controls. Persons with epilepsy were
      compared with 1) persons with migraine (PWM), whose neurological condition has
      characteristics similar to epilepsy; and 2) persons with isolated lower extremity
      fracture (PWLF). Subsequent MI was defined as a diagnosis of MI after the first
      clinical encounter for epilepsy, migraine, or lower extremity fracture (LEF); the
      association was evaluated with Cox proportional hazard modeling methods. RESULTS:
      In this study, 2.2% of PWE, 0.6% of PWM, and 1.2% of PWLF had a subsequent MI.
      Persons with epilepsy were significantly more likely to be non-Hispanic Black
      (NHB), be covered by Medicaid, and reside in a rural or low income area compared
      with PWM and PWLF. Specific cardiovascular disease risk factors were more
      prevalent in PWE than in PWM and PWLF. After adjustment, the hazard of subsequent
      MI in PWE was 48% higher than in PWM (hazard ratio (HR) = 1.48; 95% confidence
      intervals (CI) = 1.31-1.67) and 24% higher than in PWLF (HR = 1.24; 95% CI = 1.10
      1.39). The hazard of MI increased with increasing age and number of additional
      comorbidities and was higher in males, those living in rural areas, and those
      with specific cardiovascular risk factors. CONCLUSION: Persons with epilepsy had
      moderately elevated risk of subsequent MI compared with PWM or PWLF. The
      association between epilepsy and MI needs to be further investigated, and
      clinical care of PWE should include evaluation and management of risk factors for
      MI.

PMID- 30292054
TI  - Automated quantification of EEG spikes and spike clusters as a new read out in
      Theiler's virus mouse model of encephalitis-induced epilepsy.
AB  - Intracerebral infection of C57BL/6 mice with Theiler's murine encephalomyelitis
      virus (TMEV) replicates many features of viral encephalitis-induced epilepsy in
      humans, including neuroinflammation, early (insult-associated) and late
      (spontaneous) seizures, neurodegeneration in the hippocampus, and cognitive and
      behavioral alterations. Thus, this model may be ideally suited to study
      mechanisms involved in encephalitis-induced epilepsy as potential targets for
      epilepsy prevention. However, spontaneous recurrent seizures (SRS) occur too
      infrequently to be useful as a biomarker of epilepsy, e.g., for drug studies.
      This prompted us to evaluate whether epileptiform spikes or spike clusters in the
      cortical electroencephalogram (EEG) may be a useful surrogate of epilepsy in this
      model. For this purpose, we developed an algorithm that allows efficient and
      large-scale EEG analysis of early and late seizures, spikes, and spike clusters
      in the EEG. While 77% of the infected mice exhibited early seizures, late
      seizures were only observed in 33% of the animals. The clinical characteristics
      of early and late seizures did not differ except that late generalized convulsive
      (stage 5) seizures were significantly longer than early stage 5 seizures.
      Furthermore, the frequency of SRS was much lower than the frequency of early
      seizures. Continuous (24/7) video-EEG monitoring over several months following
      infection indicated that the latent period to onset of SRS was 61 (range 16-91)
      days. Spike and spike clusters were significantly more frequent in infected mice
      with late seizures than in infected mice without seizures or in mock-infected
      sham controls. Based on the results of this study, increases in EEG spikes and
      spike clusters in groups of infected mice may be used as a new readout for
      studies on antiepileptogenic or disease-modifying drug effects in this model,
      because the significant increase in average spike counts in mice with late
      seizures obviously indicates a proepileptogenic alteration.

PMID- 30292055
TI  - The rise and fall of the alveolar process: Dependency of teeth and metabolic
      aspects.
AB  - The alveolar bone has a unique capacity to follow the teeth's movements. It is
      formed around erupting teeth and their periodontal ligaments: the more the teeth
      have erupted, the larger the alveolar process. Throughout life the teeth erupt
      and migrate in an occlusal and mesial direction to compensate for attrition, an
      evolutionary trait. After tooth extraction, the alveolar process is resorbed to
      varying degrees. The mandibular alveolar bone mirrors skeletal bone condition.
      Due to fast bone turnover (which is the fastest in the whole skeleton), low bone
      mass and increased fracture risk may first be seen here. If a periapical
      radiograph of the mandibular premolars shows a dense trabeculation with well
      mineralized trabeculae and small intertrabecular spaces, it is a reliable sign of
      normal skeletal bone density (BMD) and low skeletal fracture risk, whereas a
      sparse trabecular pattern indicates osteopenia and high fracture risk. The bone
      turnover rate in the mandible is twice that of the maxilla, and may,
      hypothetically, play a role in the development of osteonecrosis of the jaw (ONJ),
      which has been found mainly in the mandibular alveolar process?

PMID- 30292056
TI  - Analytical method development of methylisothiazolinone, a preservative, in rat
      plasma using LC-MS/MS.
AB  - Methylisothiazolinone (MI) is a preservative used in consumer products to control
      bacterial and fungal growth. MI can be toxic, act as a skin sensitizer and
      irritant, and initiate lung diseases; therefore, it is important to understand
      the mechanisms underlying the toxicity of MI in the body. In this study, we
      developed a method to analyze plasma MI by using an LC-MS/MS-coupled multiple
      reaction monitoring (MRM) technique, which follows the fragments of a target
      metabolite in rat plasma. The MRM transition of MI was m/z 116 ? 101, and the
      lower limit of quantification (LLOQ) was set at 10 ng/mL. Including the
      concentration of LLOQ, a seven-point calibration curve explained much of the
      variation in the response, and it was strongly linear (R2 = 0.9998); its intra-
      and inter-day accuracy and precision values were within 15% of the standard
      deviation (SD%) and along with the FDA and Korea Ministry of Food and Drug Safety
      guidelines. For intravenous (iv) pharmacokinetic studies of MI using rats, we
      developed an analytical method that was useful in detecting the profile of MI in
      the plasma. We also determined half-life, and area under the curve (AUC) of MI
      using a non-compartment model, and these might be useful for the study of toxic
      mechanisms of MI in the body.

PMID- 30292057
TI  - Novel zwitterionic HILIC stationary phase for the determination of ethyl
      glucuronide in human hair by LC-MS/MS.
AB  - Some recent studies have described a shift from traditional reversed-phase to
      more hydrophilic LC chemistry for EtG determination in hair (hEtG). The reason
      relies on the poor retention of C8- and C18-based columns for polar compounds,
      even in presence of great amount of aqueous phase. This work presents the
      development, validation and application of a new hydrophilic interaction liquid
      chromatography-tandem mass spectrometry (HILIC-LC-MS/MS) method based on a novel
      zwitterionic stationary phase for the analysis of hEtG. The linearity was
      assessed in the range of 5-100 pg/mg hair, with a correlation coefficient of
      >0.99. The method was selective and sensitive, with a limit of detection (LOD)
      and limit of quantitation (LOQ) of 1.4 pg/mg and 4.5 pg/mg in hair, respectively.
      Suitable diagnostic sensitivity was achieved without the introduction of a sample
      purification step, or a post column solvent addition. The method was successfully
      applied to real hair samples after full validation. This method, based on a
      separation at neutral conditions, confirmed the optimum retention and thus
      selectivity for weak acids in zwitterionic HILIC columns.

PMID- 30292058
TI  - Type-I counter-current chromatography with the multilayer coil for protein
      separation.
AB  - In our recent study, the design and performance of type-I counter-current
      chromatography (CCC) were changed and improved by multilayer coil. In the present
      study, the performance of protein separation using the multilayer coil
      configuration in type-I CCC was investigated under various flow rates. In order
      to overcome the noise signal interrupting the target peaks, a hollow fiber
      membrane dialyzer was inserted between CCC column outlet and inlet of the
      monitor. The separation was performed with a two-phase solvent system composed of
      polyethylene glycol 1000/dibasic potassium phosphate each at 12.5% (w/w) in
      deionized water and lysozyme and myoglobin were used as the test samples. The
      retention of stationary phase in the head to tail elution mode was lower than
      that in the tail to head elution mode, but Rs (peak resolution) was opposite. The
      intermittently pressed tubing can efficiently improve the performance of protein
      separation by type-I CCC with the multilayer coil. The best Rs was 1.54 and
      obtained at the flow rate of 0.10 ml/min under a revolution speed of 200 rpm. The
      present result indicated that type-I CCC can be as a potential powerful tool of
      protein separation for the first time.

PMID- 30292059
TI  - Using simulation to help beginning nursing students learn about the experience of
      poverty: A descriptive study.
AB  - BACKGROUND: Increased numbers of individuals and families in the United States
      are living below the poverty level. Beginning nursing students must start to
      develop an understanding of the constraints of living in poverty and its
      relationship with health. OBJECTIVES: To describe the effects of a poverty
      simulation implemented in a freshman-level course as a beginning preparation for
      working with patients who face financial hardship. DESIGN: Descriptive study with
      a pre-test and post-test design. SETTING: School of Nursing within a private,
      religiously-affiliated university in the northeastern United States.
      PARTICIPANTS: 170 freshman-level Bachelor of Science in Nursing (BSN) students.
      METHODS: Students participated in a poverty simulation designed to sensitize
      participants to the experience and realities of living in a typical low-income
      family. Using the Undergraduate Perceptions of Poverty Tracking Survey, data were
      collected on students' general attitudes toward poverty, empathy for those living
      in poverty, and commitment to addressing poverty, two weeks prior to and one week
      after the poverty simulation experience. RESULTS: A significant decrease was
      noted in total scores from pre-simulation to post-simulation with a mean decrease
      of 7.9 +/- 10.1 points (+/-standard deviation), p < .001. Significant decreases
      were also noted in four of the six subscales, including the Welfare Attitudes,
      Poor are Different, Equal Opportunity and Lack of Resources subscales, ps < .001.
      Changes represent improvements in the students' attitudes toward poverty, empathy
      for those faced with poverty, and recognition of societal and structural barriers
      encountered by individuals living in poverty. CONCLUSIONS: This poverty
      simulation contributed to building empathy among freshman, BSN students and
      preparing them, early on, to provide more sensitive care to economically
      disadvantaged populations. Nursing programs should include similar learning
      experiences at the beginning of curricula, so that this knowledge becomes an
      integral part of the care students provide throughout their clinical experiences.

PMID- 30292060
TI  - Validation of Mentors' Behavior Scale among mentors.
AB  - BACKGROUND: The Mentors' Behavior Scale was developed and validated initially
      among nursing students by assessing the importance of mentors' behavior, showing
      satisfactory psychometrics and the potential to match mentors with students
      according to students' expectation. OBJECTIVES: This study aims to test the
      discriminant validity and the structure of the Mentor's Behavior Scale among
      mentors to assess mentors' performance. DESIGN: A cross-sectional survey was
      applied in the study. SETTING: Data were collected from mentors in seven
      hospitals in north, south, southwest China in 2016 and 2017. PARTICIPANT: 871
      mentors participated in this study. METHODS: Purposeful sampling and online
      survey was used. RESULTS: Three factors (to guide personal growth, promote
      professional development, and provide psychosocial support) were identified by
      exploratory factor analysis. The cumulative contribution of variance was 61.03%.
      The Cronbach's alpha coefficient of the scale was 0.85, and those of the three
      subscale's were 0.84, 0.72, and 0.74. The results of discriminant validity showed
      that mentors who received training and who liked mentoring students scored higher
      in mentoring behavior. CONCLUSION: Mentors considered that mentoring behavior
      were to guide students' personal growth, promote professional development and
      provide them with psychosocial support. It will be useful to apply The Mentors'
      Behavior Scale among mentors to guide and evaluate their behaviors.

PMID- 30292061
TI  - Biomechanical evaluation of the first ray in pre-/post-operative hallux valgus: A
      comparative study.
AB  - BACKGROUND: Deformity of the first ray in hallux valgus patient has been deemed
      to mainly contribute to instability of the metatarsophalangeal joint. However, it
      is not clear whether the fixation of the distal osteotomy fragment and
      transposition of the sesamoid represent the best method for hallux valgus
      treatment. The aim of this study was to examine how postoperative hallux valgus
      osteotomy affects the stability of the first ray. METHODS: To accurately
      investigate the biomechanical behavior of the first ray in pre-/postoperative
      hallux valgus patients, we described the relative displacement and stress
      distribution of the first metatarsal bone and sesamoid by imageology, test
      measurement and foot finite element model. FINDINGS: Compared with the
      preoperative hallux valgus, the plantar pressure decreased by 47.8% and was
      redistributed on second metatarsal region. The peak stress and relative
      displacement of the distal osteotomy fragment increased by +55.7% and -59.9%,
      respectively. The movement of this component shifted toward the positive sagittal
      axis direction. In addition, the relative displacement of sesamoid decreased by
      87.4% (0.18 mm) in vertical axis direction and the stress was also redistributed
      on medial and lateral region. Moreover, the strain of the medial main ligament
      was more favorable to reconstruct function of the first ray. INTERPRETATION: The
      findings showed that the osteotomy method was helpful for stability of the first
      ray. This would provide the stability suggestions for postoperative hallux valgus
      fixation and guide further rehabilitation.

PMID- 30292062
TI  - Lesser lower extremity mechanical loading associates with a greater increase in
      serum cartilage oligomeric matrix protein following walking in individuals with
      anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Aberrant mechanical loading during gait is hypothesized to contribute
      to the development of posttraumatic osteoarthritis following anterior cruciate
      ligament reconstruction. Our purpose was to determine if peak vertical ground
      reaction force and instantaneous vertical ground reaction force loading rate
      associate with the acute change in serum cartilage oligomeric matrix protein
      following a 20-minute bout of walking. METHODS: We enrolled thirty individuals
      with a unilateral anterior cruciate ligament reconstruction. Peak vertical ground
      reaction force and instantaneous vertical ground reaction force loading rate were
      extracted from the first 50% of the stance phase of gait during a 60-second
      trial. Blood samples were collected immediately before and after 20 min of
      treadmill walking at self-selected speed. The change in serum cartilage
      oligomeric matrix protein from pre- to post-walking was calculated. Stepwise
      linear regression models were used to determine the association between each
      outcome of loading and the change in serum cartilage oligomeric matrix protein
      after accounting for sex, gait speed, time since anterior cruciate ligament
      reconstruction, graft type, and history of concomitant meniscal procedure
      (DeltaR2). FINDINGS: Lesser peak vertical ground reaction force (DeltaR2 = 0.208;
      beta = -0.561; P = 0.019) and instantaneous vertical ground reaction force
      loading rate (DeltaR2 = 0.168; beta = -0.519; P = 0.037) on the anterior cruciate
      ligament reconstructed limb associated with a greater increase in serum cartilage
      oligomeric matrix protein following 20 min of walking. INTERPRETATION: Mechanical
      loading may be a future therapeutic target for altering the acute biochemical
      response to walking in individuals with an anterior cruciate ligament
      reconstruction.

PMID- 30292063
TI  - Contact force between the tibial spine and medial femoral condyle: A
      biomechanical study.
AB  - BACKGROUND: Contact between the tibial spine and medial femoral condyle with
      internal tibial rotation (ITR) has been proposed as a factor for the development
      of osteochondritis dissecans lesions. We hypothesized that tibial spine contact
      force (CF) would increase significantly with applied internal tibial torque (IT).
      METHODS: A 20 mm diameter cylinder of bone encompassing the tibial spine was
      cored and attached to a load cell. The isolated bone cylinder included the tibial
      attachments of the anterior cruciate ligament (ACL) and anterior horn of the
      lateral meniscus (AHLM). Eleven human cadaveric knees were flexed from 0 degrees 
      50 degrees  under 200 N of tibiofemoral compression (TFC), without and with 2 N-m
      IT. Tests were repeated with the AHLM cut, and again with both AHLM and ACL cut,
      where the load cell recorded CF alone without contributions from any ligamentous
      attachments. FINDINGS: There were no significant differences in CF, ITR, or
      valgus tibial rotation (VTR) after sectioning the AHLM, without or with applied
      IT. With no tibial torque, mean CFs were less than 20 N throughout the flexion
      range. Addition of IT significantly increased 1) mean CF by 44.4 N(SD 15.8 N) at
      0 degrees (+240%) and 27.2 N(SD 5.0 N) at 20 degrees (+675%), 2), mean ITR by
      10.2 degrees (SD 0.8 degrees ) at 0 degrees  flexion and 18.6 degrees (SD 2.0
      degrees ) at 20 degrees  flexion, and 3) mean VTR by 1.3 degrees (SD 0.4 degrees
      ) at 0 degrees  flexion and 4.4 degrees (SD 0.8 degrees ) at 20 degrees  flexion.
      INTERPRETATION: Our hypothesis was confirmed only between 0 degrees  and 20
      degrees  of knee flexion, where the intercondylar separation distance is
      relatively small and the possibility of tibial spine contact with ITR is greater.

PMID- 30292064
TI  - Phenotype of vigilin expressing breast cancer cells binding to the 69 nt 3'UTR
      element in CSF-1R mRNA.
AB  - Vigilin, a nucleocytoplasmic shuttling protein, post-transcriptionally suppresses
      proto-oncogene c-fms expression (encoding CSF-1R) in breast cancer by binding to
      a 69 nt cis-acting 3-UTR element in CSF-1R mRNA. CSF-1R is an important mediator
      of breast cancer development, metastasis, and survival. We confirm that vigilin
      decreases in vitro reporter luciferase activity as well as the translation rate
      of target mRNAs. We further explore the mechanism of suppression of CSF-1R. We
      show that the 69 nt binding element has profound effects on translation
      efficiency of CSF-1R mRNA, not seen in the presence of mutation of the element.
      Also, mutation of the 69 nt element in the CSF-1R mRNA 3'UTR both interferes with
      direct vigilin binding and obviates effect of vigilin overexpression on
      translational repression of CSF-1R. We show that stable vigilin binding requires
      the full length 69 nt CSF-1R element, including the 26 nt pyrimidine-rich core.
      Furthermore, titration of endogenous vigilin and other proteins which bind the 69
      nt element, by exogenously introduced CSF-1R mRNA 3'UTR containing the pyrimidine
      rich sequence, increases the adhesion, motility, and invasion of breast cancer
      cells. This phenotypic effect is not seen when the 69 nt element is deleted.
      Lastly, we are the first to show that human breast tissues exhibit strong vigilin
      expression in normal breast epithelium. Our pilot data suggest decreased vigilin
      protein expression, along with shift from the nucleus to the cytoplasmic
      location, in the transition to ductal carcinoma in situ.

PMID- 30292065
TI  - Phenotypic and Expressional Heterogeneity in the Invasive Glioma Cells.
AB  - BACKGROUND: Tumor cell invasion is a hallmark of glioblastoma (GBM) and a major
      contributing factor for treatment failure, tumor recurrence, and the poor
      prognosis of GBM. Despite this, our understanding of the molecular machinery that
      drives invasion is limited. METHODS: Time-lapse imaging of patient-derived GBM
      cell invasion in a 3D collagen gel matrix, analysis of both the cellular invasive
      phenotype and single cell invasion pattern with microarray expression profiling.
      RESULTS: GBM invasion was maintained in a simplified 3D-milieue. Invasion was
      promoted by the presence of the tumorsphere graft. In the absence of this, the
      directed migration of cells subsided. The strength of the pro-invasive repulsive
      signaling was specific for a given patient-derived culture. In the highly
      invasive GBM cultures, the majority of cells had a neural progenitor-like
      phenotype, while the less invasive cultures had a higher diversity in cellular
      phenotypes. Microarray expression analysis of the non-invasive cells from the
      tumor core displayed a higher GFAP expression and a signature of genes containing
      VEGFA, hypoxia and chemo-repulsive signals. Cells of the invasive front expressed
      higher levels of CTGF, TNFRSF12A and genes involved in cell survival, migration
      and cell cycle pathways. A mesenchymal gene signature was associated with
      increased invasion. CONCLUSION: The GBM tumorsphere core promoted invasion, and
      the invasive front was dominated by a phenotypically defined cell population
      expressing genes regulating traits found in aggressive cancers. The detected
      cellular heterogeneity and transcriptional differences between the highly
      invasive and core cells identifies potential targets for manipulation of GBM
      invasion.

PMID- 30292067
TI  - Pediatric oral Epstein-Barr virus associated self-remitting CD30+
      lymphoproliferative disorder: A distinct entity.
AB  - Epstein-Barr virus (EBV) has a well-known association with lymphoproliferative
      disorders of B and T cell origin. EBV-related B cell lymphoproliferative
      disorders include Hodgkin and Burkitt lymphomas, lymphomatoid granulomatosis, EBV
      positive diffuse large cell B cell lymphoma of the elderly, as well as B cell
      lymphomas associated with solid organ transplantation and methotrexate use. EBV
      related T cell disorders are primarily represented by NK/T- cell lymphoma. In a
      subset of patients, EBV has been implicated in CD30 positive B cell
      lymphoproliferative disorders of the oral mucosa falling under the rubric of the
      mucocutaneous ulcer of the oral cavity. We previously reported on an index series
      of endogenous CD30 positive T cell lymphoproliferative disorder of the oral
      cavity resembling borderline type C lymphomatoid papulosis. The clinical
      manifestation of type C oral lymphomatoid papulosis is that of a recurrent self
      remitting ulcer of the oral mucosa, which histologically resembles anaplastic
      large cell lymphoma. Such cases can be misdiagnosed as aggressive lymphoma
      leading to unnecessary treatment with aggressive chemotherapeutic regimens.
      Whereas none of the patients in our index series exhibited EBV positivity, here
      we discuss a very unique example of a 14-year-old girl diagnosed with EBV
      positive CD30 positive lymphoproliferative disorder strongly resembling the cases
      of intra-oral type C lymphomatoid papulosis. The patient was initially diagnosed
      by a senior hematopathology consultant as having EBV positive aggressive NK/T
      cell lymphoma. The significance of raising physician awareness regarding
      pediatric oral EBV associated CD30 positive lymphoproliferative disease of the
      oral cavity lies in preventing inadvertent exposure to toxic chemotherapeutic
      agents intended for treatment of aggressive look-alikes, namely anaplastic large
      cell lymphoma. Additionally, we include a literature review of similar reports of
      pediatric intra-oral EBV positive CD30 positive T cell lymphoproliferative
      disease.

PMID- 30292066
TI  - Targeting DDX3 in Medulloblastoma Using the Small Molecule Inhibitor RK-33.
AB  - Medulloblastoma is the most common malignant tumor that arises from the
      cerebellum of the central nervous system. Clinically, medulloblastomas are
      treated by surgery, radiation, and chemotherapy, all of which result in toxicity
      and morbidity. Recent reports have identified that DDX3, a member of the RNA
      helicase family, is mutated in medulloblastoma. In this study, we demonstrate the
      role of DDX3 in driving medulloblastoma. With the use of a small molecule
      inhibitor of DDX3, RK-33, we could inhibit growth and promote cell death in two
      medulloblastoma cell lines, DAOY and UW228, with IC50 values of 2.5 MUM and 3.5
      MUM, respectively. Treatment of DAOY and UW228 cells with RK-33 caused a G1
      arrest, resulted in reduced TCF reporter activity, and reduced mRNA expression
      levels of downstream target genes of the WNT pathway, such as Axin2, CCND1, MYC,
      and Survivin. In addition, treatment of DAOY and UW228 cells with a combination
      of RK-33 and radiation exhibited a synergistic effect. Importantly, the
      combination of RK-33 and 5 Gy radiation caused tumor regression in a mouse
      xenograft model of medulloblastoma. Using immunohistochemistry, we observed DDX3
      expression in both pediatric (55%) and adult (66%) medulloblastoma patients.
      Based on these results, we conclude that RK-33 is a promising radiosensitizing
      agent that inhibits DDX3 activity and down-regulates WNT/beta-catenin signaling
      and could be used as a frontline therapeutic strategy for DDX3-expressing
      medulloblastomas in combination with radiation.

PMID- 30292068
TI  - The erector spinae plane (ESP) block: A pooled review of 242 cases.
AB  - STUDY OBJECTIVE: The erector spinae plane block (ESPB) was first described in
      2016 as a regional block for thoracic neuropathic pain. Given its short history,
      there are a paucity of controlled clinical trials, yet an abundance of case
      reports. The primary aim of this review is to examine pooled clinical data from
      published literature to gain an understanding of ESPB characteristics. DESIGN: A
      PubMed search was conducted to identify all ESPB related publications. Inclusion
      criteria included reports of ESP single shot, continuous infusion, intermittent
      bolus, human and cadaveric studies. Only publications obtained in English were
      included. Measures included type of publication, year and country of publication,
      journal of publication, block technique, anatomic location, age, opioid and
      adjunct pain medication use, sensory and motor changes, side effects and adverse
      events. Qualitative statistics were used. MAIN RESULTS: The initial search
      yielded 201 publications. After application of inclusion and exclusion criteria,
      85 publications from 21 journals were included in the pooled review which yielded
      242 reported cases between 2016 and 2018. The majority of publications reported
      single shot techniques (80.2%), followed by intermittent boluses (12.0%) and
      continuous infusions (7.9%). 90.9% reported use of multimodal analgesia in
      addition to the ESPB and 34.7% reported sensory changes from ESPB. A reduction in
      opioid use was reported in 34.7% of cases. One adverse event involving a
      pneumothorax was reported. CONCLUSIONS: To our knowledge, this is the first
      review providing a pooled review of ESPB characteristics. The ESPB appears to be
      a safe and effective option for multiple types thoracic, abdominal, and extremity
      surgeries.

PMID- 30292069
TI  - Incidence of postoperative delirium in elderly ambulatory patients: A prospective
      evaluation using the FAM-CAM instrument.
AB  - BACKGROUND: While the incidence of postoperative delirium is high in aged
      hospitalized patients undergoing major surgery, little is known concerning
      patients undergoing ambulatory surgery. OBJECTIVE: To determine the incidence of
      postoperative delirium in aged patients after hospital discharge from an
      ambulatory surgery unit. DESIGN: Prospective observational study. PATIENTS:
      Elderly patients (>=75 years) scheduled for a surgical procedure on an ambulatory
      basis. INTERVENTIONS: Filling of the Family Confusion Assessment Method (FAM-CAM)
      questionnaire (11 items) during a phone interview of family caregivers on two
      separate occasions: five to three days before surgery, and three to five days
      after surgery. MAIN OUTCOME MEASURES: The detection of acute onset and
      fluctuating course inattention, disorganized thinking, altered level of
      consciousness, disorientation, perceptual disturbances, and psychomotor agitation
      from the observations of family caregivers. RESULTS: Signs of delirium appeared
      de novo in 2 of 141 patients (incidence 1.4%) in the postoperative period: a 80
      years old man who was disoriented and had incoherent and illogical speech on
      postoperative day 1 of resection of a cephalic cutaneous melanoma under local
      anesthesia and sedation (midazolam, sufentanil, and propofol), and a 83-years old
      woman with a pre-existing mental confusion, who experienced visual and hearing
      hallucinations and had inappropriate behaviour on postoperative day 2 of cataract
      surgery performed under episcleral block. Both patients returned to their
      preoperative states within a few days. CONCLUSIONS: Using the FAM-CAM instrument
      for the detection of postoperative delirium in ambulatory patients, the study
      showed that the incidence of cognitive changes in the ambulatory setting is very
      low. Among several putative factors, the lightness of the surgical procedure, the
      wide use of regional anesthesia, and the short hospital stay may be contributing
      factors to this result. The findings of this study need to be confirmed in a
      larger sample of patients.

PMID- 30292070
TI  - Post-traumatic stress and gambling related cognitions: Analyses in inpatient and
      online samples.
AB  - Individuals with gambling disorder (GD) report much higher rates of post
      traumatic stress symptoms and post-traumatic stress disorder (PTSS/D) than the
      general population, and individuals with both PTSS/D and GD often report much
      greater distress and impairment in daily life in comparison to individuals with
      GD alone (Grubbs, Chapman, Milner, Gutierrez, & Bradley, 2018). Despite these
      associations, little is known about the specific ways in which PTSS/D and GD
      might influence each other. To address this gap in research, the present work
      sought to examine how PTSD might be related to the expression and experience of
      gambling related cognitions. Specifically, it was hypothesized that individuals
      with PTSD or symptoms of PTSD (i.e., subclinical levels of post-traumatic stress)
      would demonstrate greater cognitive distortions and erroneous beliefs about
      gambling. To test these hypotheses, we analyzed data from two samples, an
      inpatient sample of U.S. Armed Forces veterans seeking treatment for gambling
      disorder (n = 332) and an online sample of largely recreational gambling U.S.
      adults (n = 589). Results consistently revealed that, in both samples,
      individuals with PTSD or symptoms of PTSD were likely to report greater gambling
      related cognitions. These findings persisted, even when gambling symptom severity
      and trait neuroticism were held constant. Collectively, these results suggest
      that PTSD is uniquely associated with greater cognitive distortions and erroneous
      beliefs about gambling behaviors. These findings bear distinct implications for
      current understandings of how PTSS/D and GD are related, as well as for treatment
      of individuals with dealing with this comorbidity.

PMID- 30292071
TI  - High serum uric acid is associated with oxidation of nucleosides in patients with
      type 2 diabetes.
AB  - Uric acid presents different roles in an organism, since it can act as an
      antioxidant or a pro-oxidant molecule. High serum uric acid levels may cause
      damage to several structures, including nucleic acids and its components.
      Therefore, in this study the association between increased serum uric acid
      concentrations and oxidation of nucleosides was investigated by assessment of
      urinary 8-hydroxydeoxyguanosine (8-OHdG) in patients with type 2 diabetes (T2D)
      and in healthy individuals. Urinary 8-OHdG and biochemical parameters were
      assessed in 61 patients who were initially grouped into 2 groups based on the
      median serum uric acid levels (<5.3 mg/dL and >=5.3 mg/dL). Urinary 8-OHdG was
      higher in patients with T2D and serum uric acid levels >=5.3 mg/dL, when compared
      with the patients with serum uric acid levels <5.3 mg/dL; however, co-occurrence
      of high serum uric acid with high urinary 8-OHdG was not observed in healthy
      individuals. A significant positive correlation between 8-OHdG and uric acid (r =
      0.40, P < 0.01) was observed in patients with T2D. High serum uric acid levels
      were associated with high urinary 8-OHdG levels in patients with T2D, and this
      association was independent of gender, hypertension, body mass index, and serum
      creatinine.

PMID- 30292072
TI  - Richer, wiser and in better health? The socioeconomic gradient in hypertension
      prevalence, unawareness and control in South Africa.
AB  - The socioeconomic gradient in chronic conditions is clear in the poorest and
      wealthiest of countries, but extant evidence on this relationship in low- and
      middle-income countries is inconclusive. We use data gathered between 2008 and
      2012 from a nationally representative sample of over 10,000 South African adults,
      and objective health measures to analyse the differential effects of education,
      income and other factors on the prevalence of hypertension, individuals'
      awareness and control of hypertensive status. Prevalence of hypertension is high
      at 38% among women and 34% among men. 59% of hypertensive individuals are unaware
      of their status. We find prevalence and unawareness of hypertension are a public
      health concern across all income groups in South Africa. Higher income is however
      associated with effective control amongst men. Completing secondary education is
      associated with 7 mmHg lower blood pressure only in a small sub-group of women
      but is associated with 22 percentage point higher likelihood of effective
      hypertension control amongst women. We conclude that poorer and less educated
      individuals are particularly at high risk of cardiovascular disease in South
      Africa.

PMID- 30292073
TI  - Corrigendum to 'Individual decisions to vaccinate one's child or oneself: A
      discrete choice experiment rejecting free-riding motives' Soc. Sci. Med. 207
      (2018) 106-116.

PMID- 30292074
TI  - Rapid detection method and portable device based on the photothermal effect of
      gold nanoparticles.
AB  - Gold nanoparticle (GNP)-labeled immunochromatography test strip (ICTS) has been
      widely used in different fields, but its sensitivity still require further
      improvement. In this work, a rapid and quantitative test strip detection method
      based on the photothermal effect of GNPs was established using a temperature
      sensor. A portable sensor device was fabricated based on the above method, and
      the main operating parameters were optimized. Three types of analyte models
      (cells, macromolecules, and small molecules) were chosen to evaluate the
      application of the sensor device using the commercial ICTS. The detection limit
      is at least 1 order of magnitude lower than that of the traditional visual
      detection ICTS. The other strip type of dot immunogold filtration test was
      adopted to further improve the sensitivity. The sensitivity of the sensor
      detection method was similar to that of the infrared camera method, and the
      proposed sensor device has obvious advantage of low-cost, as well as the usage of
      a small portable instrument, ease of use and rapid test. The portable sensor
      device based on the photothermal effect of GNPs can be used as a new and
      promising device for simple, quantitative, rapid, and on-site screening of
      analyte by ICTS.

PMID- 30292075
TI  - Co3O4 nanostructures on flexible carbon cloth for crystal plane effect of
      nonenzymatic electrocatalysis for glucose.
AB  - This work accounts the influence of facet effect of Co3O4 nanocrystals towards
      nonenzymatic electrocatalysis of glucose induced by different crystal planes
      modified on carbon cloth (CC) electrode. Tuning the molar ratio of precursor
      compounds during hydrothermal synthesis of Co3O4, followed by thermal
      decomposition protocols, different crystal structure including nanocubes,
      nanothorns, nanooctahedrons and nanosheets were obtained with respective {001},
      {110}, {111} and {112} facets. The electrochemical results of these different
      Co3O4 crystals demonstrate that the nanooctahedron with crystal plane of {111}
      displays the best nonenzymatic electro-catalytic glucose activity with widest
      linear range (0.5-1000 MUM), highest sensitivity (246.8 MUA mM-1) and detection
      limit of 0.012 MUM (S/N = 3). Interestingly, the electrocatalytic activity for
      nonenzymatic electro-catalytic glucose is ranked in the order of {111} > {112} >
      {110} > {001}.

PMID- 30292078
TI  - Control of adhesion and protrusion in cell migration by Rho GTPases.
AB  - Cell migration is a critical process that underpins a number of physiological and
      pathological contexts such as the correct functioning of the immune system and
      the spread of metastatic cancer cells. Central to this process are the Rho family
      of GTPases, which act as core regulators of cell migration. Rho GTPases are
      molecular switches that associate with lipid membranes and act to choreograph
      molecular events that underpin cell migration. Specifically, these GTPases play
      critical roles in coordinating force generation through driving the formation of
      cellular protrusions as well as cell-cell and cell-matrix adhesions. Here we
      provide an update on the many roles of Rho-family GTPases in coordinating
      protrusion and adhesion formation in the context of cell migration, as well as
      describing how their activity is controlled to by a variety of complex signalling
      networks.

PMID- 30292076
TI  - Altered topology of the functional speech production network in non
      fluent/agrammatic variant of PPA.
AB  - Non-fluent/agrammatic primary progressive aphasia (nfvPPA) is caused by
      neurodegeneration within the left fronto-insular speech and language production
      network (SPN). Graph theory is a branch of mathematics that studies network
      architecture (topology) by quantifying features based on its elements (nodes and
      connections). This approach has been recently applied to neuroimaging data to
      explore the complex architecture of the brain connectome, though few studies have
      exploited this technique in PPA. Here, we used graph theory on functional MRI
      resting state data from a group of 20 nfvPPA patients and 20 matched controls to
      investigate topological changes in response to focal neurodegeneration. We
      hypothesized that changes in the network architecture would be specific to the
      affected SPN in nfvPPA, while preserved in the spared default mode network (DMN).
      Topological configuration was quantified by hub location and global network
      metrics. Our findings showed a less efficiently wired and less optimally
      clustered SPN, while no changes were detected in the DMN. The SPN in the nfvPPA
      group showed a loss of hubs in the left fronto-parietal-temporal area and new
      critical nodes in the anterior left inferior-frontal and right frontal regions.
      Behaviorally, speech production score and rule violation errors correlated with
      the strength of functional connectivity of the left (lost) and right (new)
      regions respectively. This study shows that focal neurodegeneration within the
      SPN in nfvPPA is associated with network-specific topological alterations, with
      the loss and gain of crucial hubs and decreased global efficiency that were
      better accounted for through functional rather than structural changes. These
      findings support the hypothesis of selective network vulnerability in nfvPPA and
      may offer biomarkers for future behavioral intervention.

PMID- 30292077
TI  - Longitudinal changes in the mismatch field evoked by an empathic voice reflect
      changes in the empathy quotient in autism spectrum disorder.
AB  - Autism spectrum disorders (ASDs) are neurodevelopmental conditions with
      impairments in social communication and interaction. Empathy is the ability to
      understand and share another person's inner life, and it is an essential process
      in social cognition, which is deficient in ASD. The mismatch field (MMF) has been
      used as a neurophysiological marker for the automatic detection of changes in
      auditory stimuli. In the present study, we focused on long-term changes in MMF
      evoked by an empathic voice and changes in the empathy quotient (EQ) in ASD
      during an 8-week clinical trial using oxytocin (OT). Ten males with ASD without
      intellectual disability participated in this pilot study. The results
      demonstrated a significant positive correlation between the change in the MMF
      amplitude in the auditory cortex (i.e., right banks of the superior sulcus) and
      the change in the EQ score during the 8-week clinical trial, whereas no
      significant change was observed in the MMF amplitude or EQ score after the
      administration period of OT. Although we cannot conclude that the observed
      relationships were caused by OT's effect or by natural changes, our results
      suggest that MMF evoked by social voice can be a state-dependent marker of
      empathic abilities in male adults with ASD.

PMID- 30292079
TI  - Effect of subthalamic nucleus deep brain stimulation on visual scanning.
AB  - OBJECTIVE: Deep brain stimulation (DBS) can provide insights into the workings of
      the basal ganglia (BG) by interfering with their function. In patients with
      Parkinson's disease (PD) treated with DBS of the subthalamic nucleus, we studied
      the effect of DBS on scanning eye movements. METHODS: In the visual memory task,
      subjects viewed images of various complexities for later recall. In visual search
      tasks, subjects looked for and fixated one odd target ring, embedded among 48
      Landolt rings, which either stood out or not from the distractors. We compared
      the parameters of scanning saccades when DBS was on and off. RESULTS: In the
      visual memory task, DBS increased the amplitude of saccades scanning simple but
      not complex drawings. In the visual search tasks, DBS showed no effect on saccade
      amplitude or frequency. CONCLUSIONS: Saccades when viewing simple images were
      affected by DBS since they are internally guided saccades, for which the
      involvement of BG is large. In contrast, saccades when viewing complex images or
      during visual search, made with the help of visual cues in the images (externally
      guided saccades) and less dependent on BG, were resistant to the effect of DBS.
      SIGNIFICANCE: DBS affects saccades differentially depending on the task.

PMID- 30292080
TI  - Little effort with big effect - implementing the new IFCN 2017 recommendations on
      standard EEGs.

PMID- 30292081
TI  - Pulmonary rehabilitation and oropharyngeal exercises as an adjunct therapy in
      obstructive sleep apnea: a randomized controlled trial.
AB  - OBJECTIVE: It is well recognized that the most effective treatment for
      obstructive sleep apnea (OSA) is continuous positive airway pressure (CPAP).
      Different treatment possibilities comprise surgery, mandibular advancement,
      pulmonary rehabilitation, and oropharyngeal and facial exercises (PR program).
      However, these treatments showed inconsistent results. The purpose of the study
      was to compare the short-term effects of CPAP and the combination of PR program
      with CPAP on OSA severity, ventilatory functions, and changes in body
      characteristics in a newly diagnosed patient. METHODS: This study was a single
      center, two-arm, parallel, randomized, controlled, open-label trial. Forty
      patients with OSA (20 men, 20 women, aged 54.2 +/- 6.8 years) with moderate to
      severe obstructive sleep apnea were randomized to CPAP and CPAP + PR. The PR
      group underwent six weeks of 60-min twice-weekly individual PR programs. The
      primary outcome measure was apnea/hypopnea index, oxygen desaturation index, and
      Epworth Sleepiness Scale. The secondary outcome measures were a percentage of
      total sleep time with oxygen saturation below 90%, body mass index (BMI), vital
      capacity and forced expiratory volume in 1 s (% of predicted), neck, waist, and
      hip circumferences. RESULTS: Five patients with OSA did not complete the program.
      The comparison between baseline and final assessment was made in 15 patients in
      the CPAP + PR group and 20 patients in the control group with CPAP only. Although
      OSA severity was controlled with CPAP treatment in both groups, a significant
      reduction of neck, waist, and hip circumferences, BMI, and improvement of
      pulmonary function were confirmed only in the CPAP + PR group after treatment.
      CONCLUSION: Treatment with CPAP combined with the PR program improved OSA
      patients to a greater extent than only CPAP.

PMID- 30292082
TI  - Yoga and body image: How do young adults practicing yoga describe its impact on
      their body image?
AB  - This study explored the perceived impact of yoga on body image. Young adults (n=
      34 female, 12 male; Mage = 30.6 [SD = 1.6]) practicing yoga were interviewed and
      data were analyzed for emerging themes across weight status. In general,
      participants discussed the positive impact of yoga on their body image, but some
      described both a positive and negative impact. Yoga was perceived as having a
      positive impact on body image via perceived physical changes, gratitude for one's
      body, a sense of accomplishment within one's yoga practice, self-confidence, and
      witnessing different types of bodies practicing yoga. Yoga was perceived to have
      a negative impact on body image via comparative critique (e.g., upward
      comparisons with others) and inner critique (e.g., negative self-talk). Themes
      were generally similar across weight status; exceptions were that participants at
      higher weight status were more likely than those at lower weight status to
      discuss accomplishment within one's yoga practice as a positive impact on body
      image and comparative critique as a negative impact on body image. Yoga studios
      and instructors can take steps to further enhance the positive impact of yoga and
      to provide environments that are inclusive of participants with diverse body
      shapes and sizes.

PMID- 30292084
TI  - The association between suicidal ideation and lifetime suicide attempts is
      strongest at low levels of depression.
AB  - Suicidal ideation and depression alone are poor predictors of subsequent
      engagement in suicidal behavior. Evidence suggests, however, that the lethargy
      associated with depression may serve as a protective factor against suicide
      attempts. The purpose of this study was to examine whether suicidal ideation and
      depression symptoms interact in relation to lifetime suicide attempts among a
      sample of psychiatric outpatients. A sample of 739 psychiatric outpatients (Mage
      = 27.26, 60.8% female, 73.3% White/European American) from a university
      affiliated clinic completed a battery of self-report measures prior to their
      initial intake appointments. Consistent with hypotheses, a significant
      interaction emerged between suicidal ideation and depression symptoms in
      association with lifetime suicide attempts, such that the relationship between
      suicidal ideation and lifetime suicide attempts was strongest at low, as opposed
      to high, levels of depression. These findings align with previous research
      suggesting that lethargy may be a protective factor against suicide attempts, and
      conversely, that heightened arousal may serve as a suicide risk factor. Our
      results also point to a configuration of suicidal ideation and depression
      symptoms that might reflect higher suicide risk.

PMID- 30292083
TI  - Fragmentation of kidney epithelial cell primary cilia occurs by cisplatin and
      these cilia fragments are excreted into the urine.
AB  - The primary cilium, which protrudes from the cell surface, is associated with the
      pathogenesis of various diseases, including acute kidney injury (AKI). Primary
      cilium length dynamically changes during the progression of diseases. However,
      its relevance in disease and the underlying mechanism are largely unknown. In
      this study, we investigated the role of primary cilia in AKI induced by
      cisplatin, an effective anticancer drug, and the underlying mechanisms. In
      addition, we evaluated the usefulness of length alteration and deciliation of
      primary cilia into the urine for the diagnosis of AKI. Cisplatin induced
      shortening, elongation, and normalization of the primary cilia in kidney
      epithelial cells over time. During shortening, primary cilia fragments and
      ciliary proteins were excreted into the urine. During deciliation, cell
      proliferation and the expression of cyclin-dependent kinase inhibitor and
      proliferating cell nuclear antigen were not significantly changed. Shortening and
      deciliation of primary cilia were observed before significant increases in plasma
      creatinine and blood urea nitrogen concentration occurred. Pretreatment with Mito
      Tempo, a mitochondria-targeted antioxidant, prevented cisplatin-induced primary
      cilium shortening and inhibited the increases in superoxide formation, lipid
      peroxidation, blood urea nitrogen, and tissue damage. In contrast, isocitrate
      dehydrogenase 2 (Idh2) gene deletion, which results in defect of the NADPH
      associated mitochondrial antioxidant system, exacerbated cisplatin-induced
      changes in mice. Taken together, our findings demonstrate that cisplatin induces
      deciliation into the urine and antioxidant treatment prevents this deciliation,
      renal dysfunction, and tissue damage after cisplatin injection. These results
      suggest that cisplatin-induced AKI is associated with primary cilia and urine
      primary cilia proteins might be a non-invasive biomarker of kidney injury.

PMID- 30292085
TI  - Does mindfulness help people adapt to the experience of hearing voices?
AB  - Mindfulness-based interventions show promise in the treatment of psychotic
      symptoms. From a theoretical perspective, there may be several benefits of
      mindfulness for individuals who experience hearing voices. Related cross
      sectional findings suggest mindfulness may protect against distress, disruption,
      negative beliefs, dysfunctional relational style and responding, and mood
      symptoms for individuals who hear voices. To extend on previous findings, this
      study aimed to identify whether mindful relating to voices predicted voice
      related negative impacts (distress, disruption and resistance), when the
      influence of voice-topography and mood symptoms were controlled for. Overall, 62
      participants with a psychotic disorder who had experienced hearing voices in the
      previous week were given the Southampton Mindfulness of Voices Questionnaire,
      Psychotic Symptom Rating Scales, Beliefs About Voices Questionnaire, Beck
      Depression Inventory-II, and Beck Anxiety Inventory. As predicted, greater
      mindfulness of voices predicted less voice-related distress and lower resistance
      to voices. Regression analyses revealed that when associated voice topography and
      mood symptoms were controlled for, mindful relating to voices explained a
      significant proportion of variance in voice-related distress and resistance.
      Conversely, mindfulness of voices did not significantly predict voice-related
      disruption. In the context of existing literature, these findings suggest further
      mindfulness-based protocols for persistent voices should be developed and
      trialled.

PMID- 30292086
TI  - Self-efficacy and emotionally dysregulated behaviour: An exploratory test of the
      role of emotion regulatory and behaviour-specific beliefs.
AB  - We examined the relationship between self-efficacy and three behaviours that can
      serve similar affect-regulatory functions (self-injury, risky alcohol use,
      disordered eating). We proposed that general self-efficacy would be indirectly
      related to each outcome, operating via emotion regulatory self-efficacy and
      behaviour-specific self-efficacy. A path analysis confirmed this proposal in a
      sample of 490 university students, who completed questionnaires assessing the
      constructs of interest. Emotion regulatory self-efficacy was a salient predictor
      of self-injury and disordered eating, evidencing both direct and indirect
      relationships. Self-efficacy to resist each of the behaviours was uniquely
      related to its target behaviour. We discuss these findings, outlining the
      implications for a theoretical understanding of emotion-regulatory behaviours,
      and offer suggestions for prevention and early intervention initiatives.

PMID- 30292087
TI  - Antipsychotics and cardiovascular risk: A case/non-case study.
AB  - Severe mental disorders have been reported to be associated with an increased
      cardiovascular risk. To measure the potential risk excess as compared, not with
      the baseline cardiovascular risk for the general population, but with the
      cardiovascular risk associated with drug iatrogenia. 197 reported cases of
      cardiovascular adverse reaction to antipsychotic drugs as compared to the
      reported cases of this type of adverse reactions to drugs other than
      antipsychotics entered in the Spanish Pharmacovigilance System database (FEDRA)
      (1995-2018) in an observational case/non-case study. Risk estimates of
      association were reporting odds ratio (ROR), and, chi-square test (chi2). Overall
      disproportionality for the whole drug class was found [ROR 2.3 (95% CI 2.0-2.7)],
      chi2 = 127.07]. When the two types of antipsychotics (typical and atypical) were
      analysed separately, we also found statistically significant disproportionality,
      and this disproportionality is similar between both groups, with
      disproportionality measures around 2.30, with the confidence intervals not
      including the 1. The disproportionality observed suggests a risk excess that
      might be greater than expected, which holds particularly true for torsade de
      pointes, sudden death and cardiac arrhythmias in patients treated with any of the
      two types of antipsychotics. There was no significant risk for ischaemic heart
      disease.

PMID- 30292088
TI  - White matter hyperintensities are linked to future cognitive decline in de novo
      Parkinson's disease patients.
AB  - White Matter Hyperintensities (WMHs) are associated with cognitive decline in
      aging and Alzheimer's disease. However, the pathogenesis of cognitive decline in
      Parkinson's disease (PD) is not as clearly related to vascular causes, and
      therefore the role of WMHs as a marker of small-vessel disease (SVD) in PD is
      less clear. Currently, SVD in PD is assessed and treated independently of the
      disease. However, if WMH as the major MRI sign of SVD has a higher impact on
      cognitive decline in PD patients than in healthy controls, vascular pathology
      needs to be assessed and treated with a higher priority in this population. Here
      we investigate whether the presence of WMHs leads to increased cognitive decline
      in de novo PD, and if these effects relate to cortical atrophy. WMHs and cortical
      thickness were measured in de novo PD patients and age-matched controls (NPD =
      365, NControl = 174) from Parkinson's Progression Markers Initiative (PPMI) to
      study the relationship between baseline WMHs, future cognitive decline (follow
      up: 4.09 +/- 1.14 years) and cortical atrophy (follow-up: 1.05 +/- 0.10 years).
      PD subjects with high baseline WMH loads had significantly greater cognitive
      decline than i) PD subjects with low WMH load, and ii) control subjects with high
      WMH load. Furthermore, in PD subjects, high WMH load resulted in more cortical
      thinning in the right frontal lobe. Theses results show that the presence of WMHs
      in de novo PD patients predicts greater future cognitive decline and cortical
      atrophy than in normal aging.

PMID- 30292091
TI  - Immunomodulatory effect of natural and modified Citrus pectin on cytokine levels
      in the spleen of BALB/c mice.
AB  - Pectin is present in the cell wall of different vegetables and fruits. Beside its
      importance in the plant cell wall, pectin has enticed great attention for its
      beneficial effects on human health. It was shown to decrease cholesterol levels,
      to possess anti-oxidative, anti-bacterial and anti-cancer activity. The
      immunomodulatory activity of pectin and its mechanism of action is recently being
      investigated. In this study, the differential immunomodulatory activities of both
      CP (citrus pectin) and MCP (modified citrus pectin) were investigated. Females
      BALB/c mice (20-25 g) were randomly divided into 7 groups and different
      concentrations of CP and MCP (0%, 1.5%, 3% and 5%) were added to their drinking
      water for 21 days. Then, the splenic level of IL-1beta, IL-4, IL-10, IL-17, IFN
      gamma and TNF-alpha were evaluated using ELISA. Both CP and MCP exhibited
      immunomodulatory activities by increasing the levels of the pro-inflammatory
      cytokines IL-17, IFN-gamma and TNF-alpha levels. This tendency seems to be
      regulated by the up-regulation of IL-4 levels but with no major effect on those
      of IL-10. Therefore, CP and especially MCP have potential immunomodulatory
      effects which might be highly beneficial in immunotherapy.

PMID- 30292092
TI  - Viscoelastic properties of microgel thin films control fibroblast modes of
      migration and pro-fibrotic responses.
AB  - Cell behavior is influenced by the biophysical properties of their
      microenvironments, and the linear elastic properties of substrates strongly
      influences adhesion, migration, and differentiation responses. Because most
      biological tissues exhibit non-linear elastic properties, there is a growing
      interest in understanding how the viscous component of materials and tissues
      influences cell fate. Here we describe the use of microgel thin films with
      controllable non-linear elastic properties for investigating the role of material
      loss tangent on cell adhesion, migration, and myofibroblastic differentiation,
      which have implications in fibrotic responses. Fibroblast modes of migration are
      dictated by film loss tangent; high loss tangent induced ROCK-mediated amoeboid
      migration while low loss tangent induced Rac-mediated mesenchymal cell migration.
      Low loss tangent films were also associated with higher levels of myofibroblastic
      differentiation. These findings have implications in fibrosis and indicate that
      slight changes in tissue viscoelasticity following injury could contribute to
      early initiation of fibrotic related responses.

PMID- 30292090
TI  - CSF pro-orexin and amyloid-beta38 expression in Alzheimer's disease and
      frontotemporal dementia.
AB  - There is an unmet need for markers that can stratify different forms and subtypes
      of dementia. Because of similarities in clinical presentation, it can be
      difficult to distinguish between Alzheimer's disease (AD) and frontotemporal
      dementia (FTD). Using a multiplex targeted proteomic LC-MS/MS platform, we aimed
      to identify cerebrospinal fluid proteins differentially expressed between
      patients with AD and FTD. Furthermore analysis of 2 confirmed FTD genetic
      subtypes carrying progranulin (GRN) and chromosome 9 open reading frame 72
      (C9orf72) mutations was performed to give an insight into the differing
      pathologies of these forms of FTD. Patients with AD (n = 13) demonstrated a
      significant (p < 0.007) 1.24-fold increase in pro-orexin compared to FTD (n =
      32). Amyloid beta-38 levels in patients with AD were unaltered but demonstrated a
      >2-fold reduction (p < 0.0001) in the FTD group compared to controls and a
      similar 1.83-fold reduction compared to the AD group (p < 0.001). Soluble TREM2
      was elevated in both dementia groups but did not show any difference between AD
      and FTD. A further analysis comparing FTD subgroups revealed slightly lower
      levels of proteins apolipoprotein E, CD166, osteopontin, transthyretin, and
      cystatin C in the GRN group (n = 9) compared to the C9orf72 group (n = 7). These
      proteins imply GRN FTD elicits an altered inflammatory response to C9orf72 FTD.

PMID- 30292089
TI  - A meta-analytic study of experimental and chronic orofacial pain excluding
      headache disorders.
AB  - Chronic orofacial pain (COFP) disorders are prevalent and debilitating pain
      conditions affecting the head, neck and face areas. Neuroimaging studies have
      reported functional and grey matter abnormalities, but not all the studies have
      reported consistent findings. Identifying convergent abnormalities across COFPs
      provides a basis for future hypothesis-driven research aimed at elucidating
      common CNS mechanisms. Here, we perform three coordinate-based meta-analyses
      according to PRISMA guidelines to elucidate the central mechanisms of orofacial
      pain disorders. Specifically, we investigated consistent patterns of: (1) brain
      function to experimental orofacial pain in healthy subjects, (2) structural and
      (3) functional brain abnormalities in COFP. We computed our coordinate-based meta
      analyses using GingerALE. The experimental pain meta-analysis revealed increased
      brain activity in bilateral thalami, posterior mid-cingulate cortices, and
      secondary somatosensory cortices, the right posterior parietal cortex extending
      to the orofacial region of the right primary somatosensory cortex and the right
      insula, and decreased activity in the right somatomotor regions. The structural
      COFP meta-analysis identified consistent higher grey matter volume/concentration
      in the right ventral thalamus and posterior putamen of COFP patients compared to
      healthy controls. The functional COFP meta-analysis identified a consistent
      increase in brain activity in the left medial and posterior thalamus and lesser
      activity in the left posterior insula in COFP, compared to healthy controls.
      Overall, these findings provide evidence of brain abnormalities in pain-related
      regions, namely the thalamus and insula, across different COFP disorders. The
      convergence of thalamic abnormalities in both structure and function suggest a
      key role for this region in COFP pathophysiology.

PMID- 30292093
TI  - Cystic mixed adenoneuroendocrine carcinoma of the pancreas: A case report.
AB  - INTRODUCTION: Pancreatic mixed adenoneuroendocrine carcinoma (MANEC) is a rare
      tumor. We report herein a case of pancreatic MANEC with cystic features.
      PRESENTATION OF CASE: A 67-year-old woman presented with jaundice. A CT scan
      revealed an 18-mm mass at the pancreatic head that obstructed the common bile
      duct and another 35-mm cystic lesion containing a mural nodule in the pancreatic
      body, which was suspected to be an intraductal papillary mucinous carcinoma. A
      biopsy of the head mass led to the diagnosis of adenocarcinoma. The patient
      underwent pancreatoduodenectomy, and the body cyst was resected with the head
      mass. A histopathological analysis revealed that the body cyst had two
      components, ductal adenocarcinoma and neuroendocrine tumor. We diagnosed the
      cystic tumor as MANEC. DISCUSSION: Cases of MANEC have been reported as
      originating from the stomach, small intestine, and colon, but pancreatic MANEC is
      rare. The histogenesis and the therapeutic strategy for pancreatic MANEC are
      controversial. CONCLUSION: The clinicopathological features of pancreatic MANEC
      remain unclear; therefore, more reports of cases of pancreatic MANEC are
      necessary for a complete analysis.

PMID- 30292094
TI  - Mediastinal ectopic thyroid mass with normal thyroid function and location: Case
      report.
AB  - INTRODUCTION: Mediastinal Ectopic Thyroid Gland is a rare entity, accounting for
      1% of all mediastinal tumours. Here, we present a rare case of mediastinal mass
      that was proved to be an ectopic thyroid with normal thyroid function tests and
      normal thyroid gland in the cervical location. CASE PRESENTATION: A 32-year-old
      lady had a road traffic accident, with the incidental discovery of a mediastinal
      mass on chest radiography. Thyroid function tests were normal. CT scans of the
      neck and chest revealed a large mediastinal mass compressing the trachea from the
      left side and extending to the superior part of the anterior mediastinum with
      normal thyroid gland in the cervical position. Midline Partial Sternotomy was
      done with complete surgical excision of the mass. It was well circumscribed,
      multinodular, had firm inconsistency, and grossly looked like a thyroid tissue.
      Histopathology revealed ectopic thyroid tissue negative for malignancy.
      Postoperative thyroid ultrasound showed normal thyroid lobes in the neck.
      DISCUSSION: Ectopic thyroid tissue (ETT) occurs due to failure of the thyroid
      gland to migrate from foramen ceacum to its normal position in the cervical
      region in front of the trachea. The most common site of ETT is lingual thyroid
      and accounts for about 90% of all cases reported in the literature. ETT in the
      mediastinum is very rare, with only a few cases reported in the literature.
      CONCLUSION: ETT in the mediastinum is very rare and can be associated with normal
      thyroid function and normal thyroid anatomical location. It should be
      differentiated from substernal goiter.

PMID- 30292095
TI  - Transnationalism, parenting, and child disciplinary practices of African
      immigrants in Alberta, Canada.
AB  - Child discipline remains a topic of public health interest across the globe.
      Despite this enduring interest, very little is known about the child disciplinary
      practices of African immigrants in Canada. This paper explores the disciplinary
      practices of African immigrant parents in Alberta, a Canadian province with a
      recent surge in the population of African immigrants. Employing a critical
      ethnographic methodology, informed by transnational theory, we collected data
      through in-depth qualitative interviews with a purposive sample of African
      community leaders (n = 14), African immigrant parents (n = 32), policymakers (n =
      2), and health and immigrant settlement workers (n = 10). As members of the
      African immigrant community, we were deeply immersed in the research settings,
      which afforded us the opportunity to collect pertinent observational data in the
      form of reflexive notes. Thematic analysis of the data revealed child
      disciplinary approaches that incorporate Canadian and African parenting
      practices, as well as practices that appear somewhat unique to this demographic.
      We found that African immigrant parents used corporal discipline, persuasive
      discipline, and a hybrid of the two, as well as emerging practices involving
      transnational fostering and emotional isolation of children who persistently
      misbehaved. These practices, in their totality, appeared to be influenced by the
      transnational experiences of parents and precepts that are traceable to Canada's
      legal and educational systems. We present theoretical, policy, and service
      implications of our findings, including a recommendation to incorporate
      sociocultural dimensions of child discipline into Canadian child welfare policies
      and practices.

PMID- 30292096
TI  - Maternal clinical predictors of preterm birth in twin pregnancies: A systematic
      review involving 2,930,958 twin pregnancies.
AB  - In twin pregnancies, which are at high risk of preterm birth, it is not known if
      maternal clinical characteristics pose additional risks. We undertook a
      systematic review to assess the risk of both spontaneous and iatrogenic early
      (<34 weeks) or late preterm birth (<37 weeks) in twin pregnancies based on
      maternal clinical predictors. We searched the electronic databases from January
      1990 to November 2017 without language restrictions. We included studies on women
      with monochorionic or dichorionic twin pregnancies that evaluated clinical
      predictors and preterm births. We reported our findings as odds ratio (OR) with
      95% confidence intervals (CI) and pooled the estimates using random-effects meta
      analysis for various predictor thresholds. From 12, 473 citations, we included 59
      studies (2,930,958 pregnancies). The risks of early preterm birth in twin
      pregnancies were significantly increased in women with a previous history of
      preterm birth (OR 2.67, 95% CI 2.16-3.29, I2 = 0%), teenagers (OR 1.81, 95% CI
      1.68-1.95, I2 = 0%), BMI > 35 (OR 1.63, 95% CI 1.30-2.05, I2 = 52%), nulliparous
      (OR 1.51, 95% CI 1.38-1.65, I2 = 73%), non-white vs. white (OR 1.31, 95% CI 1.20
      1.43, I2 = 0%), black vs. non-black (OR 1.38, 95% CI 1.07-1.77, I2 = 98%),
      diabetes (OR 1.73, 95% CI 1.29-2.33, I2 = 0%) and smokers (OR 1.30, 95% CI 1.23
      1.37, I2 = 0%). The odds of late preterm birth were also increased in women with
      history of preterm birth (OR 3.08, 95% CI 2.10-4.51, I2 = 73%), teenagers (OR
      1.36, 95% CI 1.18-1.57, I2 = 57%), BMI > 35 (OR 1.18, 95% CI 1.02-1.35, I2 =
      46%), nulliparous (OR 1.41, 95% CI 1.23-1.62, I2 = 68%), diabetes (OR 1.44, 95%
      CI 1.05-1.98, I2 = 55%) and hypertension (OR 1.49, CI 1.20-1.86, I2 = 52%). The
      additional risks posed by maternal clinical characteristics for early and late
      preterm birth should be taken into account while counseling and managing women
      with twin pregnancies.

PMID- 30292097
TI  - Fluorescence-based kinetic analysis of miniaturized protein microarrays.
AB  - Ideal monitoring devices should enjoy a combination of characteristics, e.g. high
      sensitivity, multiplexing, portability, short time-to-result (TTR). Typically, no
      device meets all of these demands since some of them are contradictory, to some
      extent. Herein, we present a miniaturized platform based on fluorescent
      detection, which is sensitive, readily allows multiplexing, and allows real-time
      monitoring of the signal, thus allowing extraction of kinetic information as well
      as drastic reduction of TTR. This is achieved via miniaturization of active
      spots, integration with microfluidics, and algorithmic approaches. We validate
      its performance by comparing with evanescent field excitation, which obtains
      similar results, however without the addition of the necessary complex hardware.

PMID- 30292098
TI  - Ectopic expression of a Musa acuminata root hair defective 3 (MaRHD3) in
      Arabidopsis enhances drought tolerance.
AB  - Genetic improvement is an important approach for crop improvement towards yield
      stability in stress-prone areas. Functional analysis of candidate stress response
      genes can provide key information to allow the selection and modification of
      improved crop varieties. In this study, the constitutive expression of a banana
      cDNA, MaRHD3 in Arabidopsis improved the ability of transgenic lines to adapt to
      drought conditions. Transgenic Arabidopsis plants expressing MaRHD3 had roots
      with enhanced branching and more root hairs when challenged with drought stress.
      The MaRHD3 plants had higher biomass accumulation, higher relative water content,
      higher chlorophyll content and an increase in activity of reactive oxygen species
      (ROS) scavenging enzymes; SOD, CAT, GR, POD and APX with reduced water loss rates
      compared to control plants. The analysis of oxidative damage indicated lower cell
      membrane damage in transgenic lines compared to control plants. These findings,
      together with data from higher expression of ABF-3 and higher ABA content of
      drought-stressed transgenic MaRHD3 expressing plants, support the involvement of
      the ABA signal pathway and ROS scavenging enzyme systems in MaRHD3 mediated
      drought tolerance.

PMID- 30292099
TI  - Trimethylamine in postmortem tissues as a predictor of postmortem interval
      estimation using the GC method.
AB  - Trimethylamine (TMA), a simple amine in volatile compounds, indicating the
      spoilage degree of meat, related with the late postmortem interval (PMI) during
      the cadaver decomposition process. In this paper, a headspace gas chromatography
      (HS-GC) method has been successfully built to analyze the content of TMA in
      postmortem rat tissues (liver, myocardial and skeletal muscle tissues), which is
      used for PMI estimation with the wide range of PMI (0-720 h postmortem) at 16 
      degrees C +/- 1  degrees C. Correspondingly, three equations about the
      relationship between the PMI and TMA content were established, in which they
      showed that the TMA content in all three tissues increased from the firstly
      detected time to 192 h and gradually decreased after 384 h. Furthermore, the TMA
      measurement in five human samples was carried out and the results (<35 h PMI)
      showed a good agreement about the change trend of TMA content between human and
      rat, which elucidated that this research might provide a new insight for the
      forensic scientist to band HS-GC technology together with TMA determination in
      the PMI estimation.

PMID- 30292100
TI  - Dynamic evaluation of simulated leg length inequalities and their effects on the
      musculoskeletal apparatus.
AB  - BACKGROUND: Leg length inequalities (LLI) are a common problem in medicine. So
      far, the diagnosis and treatment are performed under static conditions. Surface
      Topography (ST) is an optical, non-invasive technique that uses the principle of
      triangulation to measure spinal posture and pelvic position. This technique
      offers the opportunity to detect and treat LLIs and their effects under dynamic
      conditions. RESEARCH: question The aim of the study is to show that ST can detect
      simulated LLIs under dynamic conditions and to prove if there are differences
      between the effects on the human body under static and dynamic conditions.
      METHODS: In the clinical study a total of 30 test subjects were examined with a
      ST measuring device. LLIs (1 to 4 cm) were simulated using a custom- built sandal
      and insoles of various thickness. The pelvic obliquity, the surface rotation and
      lateral deviation of the spine were detected on a treadmill under static and
      dynamic conditions (3 km/h). RESULTS: Under static and dynamic conditions LLIs
      lead to a significant increase of all measured parameters. The pelvic obliquity
      reaches a significant level of p < 0.0001 under static and p = 0.0001-0.0421
      under dynamic conditions. However, for all examined parameters the magnitudes of
      the parameters under dynamic conditions were smaller than under static
      conditions. SIGNIFICANCE: The study showed that simulated LLIs also have a
      significant effect on the human pelvis and spine under dynamic conditions, but
      with a smaller magnitude than under static conditions. The human individuum is a
      dynamic one. Because of that, for the future it should be of great interest to
      use dynamic measurements to detect and treat LLIs to provide an over correction
      of LLIs.

PMID- 30292101
TI  - Hypnotic and non-hypnotic suggestion to ignore pre-cues decreases space-valence
      congruency effects in highly hypnotizable individuals.
AB  - Previous studies have shown that the speed of identifying emotional words is
      affected by pre-cues of up or down arrows, called the space-valence congruency
      effect (Zhang, Hu, Zhang, & Wang, 2015). In the present study, we investigate
      whether this effect is influenced by hypnotic or non-hypnotic suggestions to
      ignore pre-cues in highly hypnotizable individuals (HHIs). In all conditions,
      target words (including positive words, negative words and neutral words) primed
      by up or down arrows were presented to pre-screened HHIs. They were asked to
      identify whether the target words had emotional valence. Behavioral results
      showed that the space-valence congruency effect was absent in the hypnotic and
      non-hypnotic suggestion groups, but present in the non-suggestion control group.
      Consistently, the amplitudes of P2 components elicited by negative words were
      significantly larger when primed by down than by up arrows in the non-suggestion
      control group, and this P2 effect was absent in the hypnotic and non-hypnotic
      suggestion groups. Moreover, the amplitudes of the late positive components (LPC)
      showed no significant arrow-priming difference for positive targets in the
      hypnotic-suggestion and control groups. However, in the non-hypnotic suggestion
      group, the amplitudes of LPC were significantly larger when primed by down than
      up arrows for positive targets. Our results showed that suggestions, even without
      a hypnotic induction, can de-automatize embodied emotional recognition processes
      and modulate early attentional processing.

PMID- 30292102
TI  - Biomimetic lipophilic activated carbon for enhanced removal of triclosan from
      water.
AB  - Triclosan, an antimicrobial micro-pollutant with a high bio-accumulation
      potential represented by its high octanol-water partition coefficient (log Kow)
      of 4.76 is commonly encountered in water and wastewater worldwide. The present
      study focuses on biomimetic surface modification of commercial activated carbon
      (PAC) with long chain fatty acid namely docosahexaenoic acid (DHA) resulting in
      enhanced affinity for the hydrophobic micro-pollutant; triclosan (TCS). The
      sorption process of the resulting modified lipophilic carbon (PACM) was
      investigated for the effect of various experimental conditions. The Freundlich
      isotherm and pseudo-second-order kinetic models had a better fit. PACM exhibited
      the maximum adsorption capacity of 395.2 mg g-1 in contrast to 71.5 mg g-1
      obtained for PAC. The surface morphology in terms of surface area, surface
      acidity, pore size, contact angle, etc. and were also evaluated. The contact
      angle of 134.3 degrees  obtained for PACM confirmed its highly hydrophobic
      nature. The efficacy of PACM was also evaluated using real-world secondary
      treated effluent containing triclosan confirming its applicability for tertiary
      treatment of wastewater. The study established that the biomimetic approach of
      creating lipid-like sites on the carbon surface results in the enhanced removal
      of lipophilic micro-pollutants. It can also be utilized for the removal and
      recovery of a wide variety of other organic micro-pollutants.

PMID- 30292103
TI  - Copper benzene-1,3,5-tricarboxylate (Cu-BTC) metal-organic framework (MOF) and
      porous carbon composites as efficient carbon dioxide adsorbents.
AB  - The development of novel porous materials for CO2 capture and storage has
      received increasing attention due to the global warming problem. The aim of this
      work was to develop novel composites by merging Cu-BTC framework and porous
      carbon materials, including ordered mesoporous non-activated carbon (OMC),
      ordered mesoporous activated carbon (AC), and nitrogen-containing microporous
      carbon (NC) as efficient adsorbents for CO2 capture. The morphology, porosity and
      surface area of the parent materials and composites were fully characterized. All
      resulting composites were identified as microporous materials with type I
      adsorption isotherm. During synthesis of these composites, additional micropores
      were formed in the interfacial region between heterogeneous phases, which greatly
      enhances both their specific surface area and porosity. As compared to the parent
      materials, namely carbons and Cu-BTC, the CO2 uptake capability of the composites
      is greatly enhanced due to the presence of micropores at the interface.
      Specifically, NC-Cu-BTC composite exhibited the highest CO2 capacity with ~8.24
      and ~4.51 mmol/g under 1 bar at 0 and 25  degrees C, respectively. These novel
      porous carbon/MOF composites may have great potential for adsorption application
      including CO2 capture.

PMID- 30292104
TI  - Tannic acid-inspired paclitaxel nanoparticles for enhanced anticancer effects in
      breast cancer cells.
AB  - Paclitaxel (PTX) is a gold standard chemotherapeutic agent for breast, ovarian,
      pancreatic and non-small cell lung carcinoma. However, in clinical use PTX can
      have adverse side effects or inadequate pharmacodynamic parameters, limiting its
      use. Nanotechnology is often employed to reduce the therapeutic dosage required
      for effective therapy, while also minimizing the systemic side effects of
      chemotherapy drugs. However, there is no nanoformulation of paclitaxel with
      chemosensitization motifs built in. With this objective, we screened eleven
      pharmaceutical excipients to develop an alternative paclitaxel nanoformulation
      using a self-assembly method. Based on the screening results, we observed tannic
      acid possesses unique properties to produce a paclitaxel nanoparticle
      formulation, i.e., tannic acid-paclitaxel nanoparticles. This stable TAP
      nanoformulation, referred to as TAP nanoparticles (TAP NPs), showed a spherical
      shape of ~ 102 nm and negative zeta potential of ~ -8.85. The presence of PTX in
      TAP NPs was confirmed by Fourier Transform Infrared (FTIR) spectra,
      thermogravimetric analyzer (TGA), and X-ray diffraction (XRD). Encapsulation
      efficiency of PTX in TAP NPs was determined to be >=96%. Intracellular drug
      uptake of plain drug PTX on breast cancer cells (MDA-MB-231) shows more or less
      constant drug levels in 2 to 6 h, suggesting drug efflux by the P-gp
      transporters, over TAP NPs, in which PTX uptake was more than 95.52 +/- 11.01% in
      6 h, as analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      Various biological assays such as proliferation, clonogenic formation, invasion,
      and migration confirm superior anticancer effects of TAP NPs over plain PTX at
      all tested concentrations. P-gp expression, beta-tubulin stabilization, Western
      blot, and microarray analysis further confirm the improved therapeutic potential
      of TAP NPs. These results suggest that the TAP nanoformulation provides an
      important reference for developing a therapeutic nanoformulation affording
      pronounced, enhanced effects in breast cancer therapy.

PMID- 30292105
TI  - Assembly of pi-functionalized quaternary ammonium compounds with graphene
      hydrogel for efficient water disinfection.
AB  - Graphene hydrogels hold great potential for the disinfection of bacteria
      contaminated water. However, the intrinsic antibacterial activity of graphene
      hydrogels is not satisfactory, and the incorporation of other antibacterial
      agents often results in their unwanted releases. Here, we present a new strategy
      to improve the antibacterial activities of graphene hydrogels. We first
      synthesized a new pi-conjugated molecule containing five aromatic rings and two
      side-linked quaternary ammonium (QA) groups, denoted as piQA. Next, we fabricated
      composite gravity filters by assembling piQA with reduced graphene oxide (rGO)
      hydrogel. The rGO hydrogel helps to form a sponge-like physical sieve,
      contributes to the overall antibacterial activity, and provides abundant pi-rich
      surfaces. The large aromatic cores of piQA allow the formation of collectively
      strong pi-pi interactions with rGO, resulting in a high piQA mass loading of ~31
      wt%. Due to the sieving effect of rGO hydrogel and the synergistic antibacterial
      activity of rGO and piQA, the filters prepared based on piQA-rGO assemblies can
      remove over 99.5% of Gram-negative Escherichia coli (E. coli) and Gram-positive
      Staphylococcus aureus (S. aureus) cells with a high-water treatment capacity of
      10 L g-1. Furthermore, the piQA-rGO assemblies show low toxicity towards two
      different mammalian cell lines (L929 and macrophages), and the release of piQA is
      also negligible. Overall, the new piQA-rGO assembly demonstrates high potential
      for water disinfection applications.

PMID- 30292106
TI  - Understanding the adsorption of sulfonamide antibiotics on MIL-53s: Metal
      dependence of breathing effect and adsorptive performance in aqueous solution.
AB  - This investigation is based on experimental data to deeply understand the unusual
      adsorption behavior of the flexible MIL-53s in aqueous solution. In contrast to
      the strongly flexible MIL-53(Cr) and MIL-53(Al) with large pore form (lp) in
      water and in their anhydrous state, MIL-53(Fe) exhibits narrow pore form (np) or
      very narrow pore form (vnp), indicating that breathing effect depends on the
      nature of the metal. Sulfamethoxazole (SMZ) adsorption results demonstrated that
      the maximum adsorption capacities predicted by Langmuir model were 1.85, 1.78 and
      0.314 mmol/g for MIL-53(Cr), MIL-53(Al), and MIL-53(Fe), respectively. The
      adsorption equilibrium was rapidly reached within 60 min and the kinetic data
      best fitted with the pseudo second order model. The lp form of MIL-53(Cr) and MIL
      53(Al) in aqueous solution provided the easy entrance for contaminants, lead to
      lower binding energy and caused modifications of the hydrophobic/hydrophilic
      character, which all enhanced their adsorption capacities for SMZ. However, the
      np form of MIL-53(Fe) with small inner pores and hydrophilicity compromised its
      adsorption capacity for SMZ. The experimental results revealed electrostatic
      interactions, hydrogen bonding, and pi-pi interaction/stacking contributed to the
      adsorption of SMZ on MIL-53s as well. In summary, the complexation of different
      metal nodes to MOFs is accompanied by the diversity of properties, which
      significantly affect their adsorptive performance.

PMID- 30292107
TI  - Liraglutide modulates gut microbiota and reduces NAFLD in obese mice.
AB  - Metabolic disorders such as insulin resistance and diabetes are associated with
      obesity and nonalcoholic fatty liver disease (NAFLD). The aggressive form of a
      fatty liver disease may progress to cirrhosis and hepatocellular carcinoma.
      Furthermore, recent studies demonstrated that there is a dysbiosis in the gut
      microbiota associated with early stages of metabolic disease. Therefore, the
      identification and repurposing of drugs already used to treat insulin resistance
      may be an excellent option for other disorders. We evaluated the effect of
      liraglutide on obesity, NAFLD and gut microbiota modulation in two different
      animal models of obesity: the ob/ob mice and the high-fat diet (HFD)-fed mice.
      Liraglutide treatment induced significant weight loss in both obesity models,
      showed improvements in glycemic parameters and reduced inflammatory cell
      infiltration in the cecum and the liver. In ob/ob mice, the liraglutide treatment
      was able to reduce the accumulation of liver fat by 78% and reversed steatosis in
      the HFD mice. The gut microbiota analysis showed that liraglutide changed the
      overall composition as well as the relative abundance of weight-relevant
      phylotypes such as a reduction of Proteobacteria and an increase of Akkermansia
      muciniphila in the treated HFD group. We show that liraglutide can lead to weight
      loss and gut microbiota modulations, and is associated with an improvement of
      NAFLD. Furthermore, by generating a profile of the intestinal microbiota, we
      compiled a list of potential bacterial targets that may modulate metabolism and
      induce a metabolic profile that is considered normal or clinically controlled.

PMID- 30292108
TI  - Effect of Fe3O4 NPs application on fluoride (F) accumulation efficiency of
      Prosopis juliflora.
AB  - Fluoride (F) pollution is a major worldwide problem affecting approximately 200
      million people. Hyperaccumulator plant Prosopis juliflora has been used for the
      removal of F from contaminated soils; however it's low F accumulation efficiency
      and low biomass limits the phytoremediation efficiency. Present study deals with
      enhancement of F uptake efficiency of plant P. juliflora through iron oxide
      nanoparticles (Fe3O4 NPs) application for remediation of agricultural soils. For
      the study, Fe3O4 NPs were synthesized through green route using waste jojoba
      leaves. The application of Fe3O4 NPs significantly increased the shoot and root
      length of plant P. juliflora. Fe3O4 NPs treatment also promoted the F
      accumulation in shoot and root tissues upto 28.43 and 34.64 mg kg-1,
      respectively. Microscopic (FESEM and light microscopic) and EDX spectrum analysis
      of plant tissues confirmed the accumulation and translocation of Fe3O4 NPs and F
      in plant tissues This nano-phytoremediation approach could be a better option for
      F remediation for agricultural and commercial purpose.

PMID- 30292109
TI  - Antioxidant systems responses and the compatible solutes as contributing factors
      to lead accumulation and tolerance in Lathyrus sativus inoculated by plant growth
      promoting rhizobacteria.
AB  - Short-term lead (Pb) uptake by plants is important to better understand the
      mechanisms of metal uptake, plant tolerance and detoxification strategy. Thus we
      examined the response of Lathyrus sativus to 1 mM Pb application in hydroponic
      sorption kinetics at 24, 48 and 72 h, and we investigated the contribution of two
      inocula I1 (R. leguminosarum (M5) + B. simplex + Luteibacter sp + Variovorax sp)
      and I5 (R. leguminosarum (M5) + P. fluorescens (K23) + Luteibacter sp +
      Variovorax sp) in plant mechanisms responses. Pb application induced its
      immediate uptake by L. sativus with highest concentrations, which increased
      gradually mostly for inoculated plants. The control plant shoots accumulated the
      highest concentration of lead at 24 h. However, at 48 and 72 h this potential
      uptake was significantly enhanced in plants inoculated with I5. Moreover,
      inoculation increased significantly root Pb-uptake with the maximum reached at 72
      h. We observed a progressive decline in chlorophyll contents after Pb exposure in
      control plants that was higher than in PGPR-treated plants and the greatest
      improvement (152%) was recorded in I5 inoculated leaves. The PGPR also promoted
      significant elevation in the carotenoid content with the highest increases (188%)
      in plants inoculated with I5 at 72 h. Data illustrated remarkable augmentation in
      malondialdehyde, ion leakage level and decrease in membrane stability. Whereas,
      inoculation enhanced significantly cellular membrane integrity through increases
      in membrane stability index as compared to the control plants. In response to Pb,
      proline biosynthesis, as well as total soluble sugars concentration, immediately
      increased and the stimulatory effect was more pronounced in inoculated plants at
      72 h. Lead considerably altered the activities of SOD, GPOX, CAT and APX enzymes
      in leaves and roots in a time- and inoculation- dependent manner. It is concluded
      that antioxidant enzymes, carotenoids, soluble sugars and proline were involved
      in the main defense mechanism and tolerance of Lathyrus sativus to Pb oxidative
      stress, as well lead accumulation, and are likely to operate in combination.

PMID- 30292110
TI  - Effect of Fe(II) on reactivity of heterotrophic denitrifiers in the remediation
      of nitrate- and Fe(II)-contaminated groundwater.
AB  - Heterotrophic denitrifiers, capable of simultaneous nitrate reduction and Fe(II)
      oxidation, can be applied for the remediation of nitrate and Fe(II) combined
      contamination in groundwater. Under strictly anaerobic condition, denitrifying
      microbial communities were enriched with the coexistence of soluble nitrate,
      Fe(II) and associated nutrient elements to monitor the denitrification process.
      Low abundance of Fe(II) (e.g., 10 mg L-1 in this study) tended to stimulate the
      activity of denitrifying microbial communities. However, elevated Fe(II)
      concentration (50 and 100 mg L-1 in this study), acted as a stress, strongly
      inhibited the activity and reproduction of denitrifiers. Besides, through
      thermodynamics calculations, methanol rather than Fe(II) was proved to be the
      preferable electron donors for both energy metabolism and anabolism.
      Betaproteobacteria was found to be the most predominant (sub)phylum in all
      enriched microbial assemblages. Methylovesartilis was the most predominant group
      mainly catalyzed for methanol based denitrification, and others denitrifiers
      included Methylophilaceae, Dechloromonas and Denitratisoma. Excessive Fe(II) in
      the solution greatly reduced the proportions of these denitrifying groups, while
      the influence seemed to be less apparent on functional genes composition. As
      such, a conceptional metabolism pathway of the most dominant genus (i.e.,
      Methylovesartilis) for nitrate reducing as well as methanol and Fe(II) oxidation
      confirmed that biotic nitrate reducing and Fe(II) oxidizing were potentially
      proceeded in cytoplasm by enzymes such as NarGHI. The Fe(II) oxidation rate
      depended on the rate of Fe(II) entering into the cell. These findings provide a
      clear mechanistic understanding of heterotrophic denitrification coupling with
      Fe(II) oxidation, and environmental implication for the bioremediation of nitrate
      and Fe(II) contaminated groundwater.

PMID- 30292111
TI  - Characterization of the dissociation kinetics of Cd and Ni in soils based on
      diffusive gradients in thin films technique.
AB  - A new theoretical method was established for the combinatorial calculation of the
      dissociation rate constant (K-1) of the metal-organic complexes (MLs), the
      concentration of free ionic soil metals (CM), the labile concentration of soil
      metal-organic complexes (CML) based on diffusive gradients in thin-films (DGT)
      technique with a range of diffusive layer thicknesses (0.053-0.173 mm) in soils.
      The fitting results agreed well with the determined values. The values of K-1,
      CML and CM were calculated without other morphological analysis software and the
      fitting results agreed well with the determined values with some advantages such
      as the use of fewer hypothetical parameters, ease of calculation, the full
      embodiment of the contribution of MLs to the labile content. According to the
      results of model fitting, cation exchange capacity and soil organic matter were
      found to be the key environmental factors for K-1 values of Cd and Ni,
      respectively. The labile contents of Cd and Ni in soil were closely related with
      pH, soil organic matter and the total contents of heavy metals.

PMID- 30292112
TI  - Complexation of U(VI) with Cucurbit[5]uril: Thermodynamic and Structural
      investigation in aqueous medium.
AB  - The assessment of cucurbituril (CBn) for selective removal of actinides from
      nuclear waste streams requires comprehensive understanding of binding parameters
      and coordination of these complexes. The present work is the first experimental
      report on complexation of actinide ion with Cucurbit[5]uril (CB5) in solution.
      The thermodynamic parameters (DeltaG, DeltaH and DeltaS) for complexation of CB5
      with U(VI) in formic acid water medium were determined using microcalorimetry and
      UV-Vis spectroscopy. The enthalpy and entropy of complexation revealed the
      partial binding of U(VI) to CB5 portal. The partial binding was confirmed by
      spectroscopic techniques viz. extended X absorption fine structure spectroscopy
      (EXAFS), 1H and 13C NMR. The EXAFS chi(r) versus r spectra for U-CB5 complex has
      been fitted from 1.4 to 3.5 A with two oxygen shells and a carbon shell. The
      presence of three carbon atom in secondary shell shows the involvement of only
      three carbonyl oxygens directly bonding to U(VI) which is in contrast to that
      calculated from gas phase DFT calculation of unhydrated system. The combined
      effect of hydration and formic acid encapsulation led to the enhanced stability
      of partially bound U(VI) to CB5. In the present work the binding of formic acid
      has also been studied by fluorescence spectroscopy. ESI-MS data shows the unusual
      stabilization of U(VI) by CB5 in gas phase.

PMID- 30292113
TI  - Defunct gold mine tailings are natural reservoir for unique bacterial communities
      revealed by high-throughput sequencing analysis.
AB  - Mine tailing dumps are arguably one of the leading sources of environmental
      degradation with often both public health and ecologically consequences. The
      present study investigated the concentration of heavy metals in gold mine
      tailings, and used high throughput sequencing techniques to determine the
      microbial community diversity of these tailings using 16S rRNA gene based
      amplicon sequence analysis. The concentration of detected metals and metalloids
      followed the order Si > Al > Fe > K > Ca > Mg. The 16S rRNA gene based sequence
      analysis resulted in a total of 273,398 reads across the five samples,
      represented among 7 major phyla, 41 classes, 77 orders, 142 families and 247
      major genera. Phylum Actinobacteria was the most dominant, followed by
      Proteobacteria, Firmicutes, Chloroflexi, Cyanobacteria, Bacteroidetes,
      Acidobacteria and Planctomycetes. Redundancy analysis (RDA) and pairwise
      correlation analysis positively correlated the distribution of
      Alphaproteobacteria and Gammaproteobacteria to Al and K; Actinobacteria to Cr and
      Chloroflexi to Si. Negative correlations were observed in the distribution of
      Bacteroidetes with respect to As concentrations, Actinobacteria to Al, and
      Alphaproteobacteria and Gammaproteobacteria to high As and Te content of the
      soils. Predictive functional analysis showed the presence of putative
      biosynthetic and degradative pathways across the five sample sites. The study
      concludes that mine tailing sites harbour diverse and unique microbial
      assemblages with potentially biotechnologically important genes for biosynthesis
      and biodegradation.

PMID- 30292114
TI  - Environmental assessment of solar photo-Fenton processes in combination with
      nanofiltration for the removal of micro-contaminants from real wastewaters.
AB  - Scarcity of water and concerns about the ecotoxicity of micro-contaminants are
      driving an interest in the use of advanced tertiary processes in wastewater
      treatment plants. However, the life cycle environmental implications of these
      treatments remain uncertain. To address this knowledge gap, this study evaluates
      through life cycle assessment the following four advanced process options for
      removal of micro-contaminants from real effluents: i) solar photo-Fenton (SPF)
      operating at acidic pH; ii) acidic SPF coupled with nanofiltration (NF); iii) SPF
      operating at neutral pH; and iv) neutral SPF coupled with NF. The results show
      that acidic SPF coupled with NF is the best option for all 15 impacts considered.
      For example, its climate change potential is almost three times lower than that
      of the neutral SPF process (311 vs 928 kg CO2 eq./1000 m3 of treated effluent).
      The latter is the worst option for 12 impact categories. For the remaining three
      impacts (acidification, depletion of metals and particulate matter formation),
      acidic SPF without NF is least sustainable; it is also the second worst option
      for seven other impacts. Neutral SPF with NF is the second worst technology for
      climate change, ozone and fossil fuel depletion as well as marine eutrophication.
      In summary, both types of SPF perform better environmentally with than without NF
      and the acidic SPF treatment is more sustainable than the neutral version. Thus,
      the results of this work suggest that ongoing efforts on developing neutral SPF
      should instead be focused on further improvements of its acidic equivalent
      coupled with NF. These results can also be used to inform future development of
      policy related to the removal of micro-contaminants from wastewater.

PMID- 30292115
TI  - In situ arsenic speciation and the release kinetics in coastal sediments: A case
      study in Daya Bay, South China Sea.
AB  - In-situ study on arsenic speciation and the release kinetics in marine sediments
      was scarce. In this study, the distributions of labile As and their speciation in
      coastal sediments of Daya Bay were obtained by separate diffusive gradients in
      thin films (DGT) probes. Results showed that the DGT-labile As(V) was the main
      speciation in surface sediments (from -20 to 0 mm) with a concentration range of
      0.07-3.05 MUg.L-1, while the labile As(III) was the main speciation in deep
      layers of sediments (from -100 to -20 mm). In coastal areas, mariculture farms
      was the most dominated contributor to As(V) contamination in surface sediments.
      Both the apparent diffusion flux estimation and the DGT induced flux in sediments
      (DIFS) simulation indicated that As(V) contamination in surface sediments of
      mariculture, harbor and petrochemical areas suffered the potential risk of As(V)
      release into the overlying water from sediments. DIFS modeling also found that
      the sediments of mariculture farms were the main sediment As pools. Linear
      regression analysis indicated that the mobility of As mainly attributed to the
      As(V) in sediments.

PMID- 30292116
TI  - Activated carbons of varying pore structure eliminate the bioavailability of
      2,3,7,8-tetrachlorodibenzo-p-dioxin to a mammalian (mouse) model.
AB  - The use of activated carbon (AC) as an in situ sorbent amendment to sequester
      polychlorinated-dibenzo-p-dioxins and furans (PCDD/Fs) present in contaminated
      soils and sediments has recently gained attention as a novel remedial approach.
      This remedy could be implemented at much lower cost while minimizing habitat
      destruction as compared to traditional remediation technologies that rely on
      dredging/excavation and landfilling. Several prior studies have demonstrated the
      ability of AC amendments to reduce pore water concentrations and hence
      bioaccumulation of PCDD/Fs in invertebrate species. However, our recent study was
      the first to show that AC had the ability to sequester 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD) in a form that eliminated bioavailability to a mammalian (mouse)
      model. Here we show that three commercially available ACs, representing a wide
      range of pore size distributions, were equally effective in eliminating the
      bioavailability of TCDD based upon two sensitive bioassays, hepatic induction of
      cyp1A1 mRNA and immunoglobulin M antibody-forming cell response. These results
      provide direct evidence that a wide range of structurally diverse commercially
      available ACs may be suitable for use as in situ sorbent amendments to provide a
      cost-effective remedy for PCDD/F contaminated soils and sediments. Potentially,
      adaption of this technology would minimize habitat destruction and be protective
      of ecosystem and human health.

PMID- 30292117
TI  - Vent pipe emissions from storage tanks at gas stations: Implications for setback
      distances.
AB  - At gas stations, fuel vapors are released into the atmosphere from storage tanks
      through vent pipes. Little is known about when releases occur, their magnitude,
      and their potential health consequences. Our goals were to quantify vent pipe
      releases and examine exceedance of short-term exposure limits to benzene around
      gas stations. At two US gas stations, we measured volumetric vent pipe flow rates
      and pressure in the storage tank headspace at high temporal resolution for
      approximately three weeks. Based on the measured vent emission and meteorological
      data, we performed air dispersion modeling to obtain hourly atmospheric benzene
      levels. For the two gas stations, average vent emission factors were 0.17 and
      0.21 kg of gasoline per 1000 L dispensed. Modeling suggests that at one gas
      station, a 1-hour Reference Exposure Level (REL) for benzene for the general
      population (8 ppb) was exceeded only closer than 50 m from the station's center.
      At the other gas station, the REL was exceeded on two different days and up to
      160 m from the center, likely due to non-compliant bulk fuel deliveries. A
      minimum risk level for intermediate duration (>14-364 days) benzene exposure (6
      ppb) was exceeded at the elevation of the vent pipe opening up to 7 and 8 m from
      the two gas stations. Recorded vent emission factors were >10 times higher than
      estimates used to derive setback distances for gas stations. Setback distances
      should be revisited to address temporal variability and pollution controls in
      vent emissions.

PMID- 30292118
TI  - Contrasting impacts of long-term application of manure and crop straw on residual
      nitrate-N along the soil profile in the North China Plain.
AB  - The effects of long-term animal manure application and crop straw incorporation
      on the migration of carbon (C) and nitrogen (N) deep into the soil profile and
      the associated N leaching risk in particular have not been thoroughly elucidated
      to date. Soil profile samples were collected from depths of up to 200 cm from the
      following four treatments in a 27-year field experiment on the North China Plain:
      N + phosphorus (P) + potassium (K) fertilizers (NPK), NPK + 22.5 t ha-1 swine
      manure (NPKM), NPK + 33.7 t ha-1 swine manure (NPKM+) and NPK + straw
      incorporation (NPKS). The results revealed that long-term manure application and
      straw incorporation significantly enhanced the soil organic C (SOC) and total N
      (TN) contents in the upper 20 cm and that this effect was weaker in the deeper
      soil layers (P < 0.05). Residual nitrate-N (NO3--N) contents at 0 to 40 cm and
      120 to 200 cm in the NPKM and NPKM+ were 4-16 and 2-9 times higher than those in
      the NPK and NPKS, respectively. These results indicated a greater potential for N
      leaching from manure addition and a higher propensity for NO3--N leaching out of
      the 40-100 cm soil layer. Pearson relationship analysis demonstrated that NO3--N
      content was clearly affected by SOC and dissolved organic N (DON) contents along
      the soil profile (20-200 cm), implying that the higher residual NO3--N contents
      in the deeper soil from manure addition were partially attributable to the
      mineralization and nitrification of the downward SOC and DON. Interestingly, a
      low level of residual NO3--N combined with negative mineralization in the 120-200
      cm soil layers of the NPKS treatment was observed, suggesting that straw
      incorporation promotes soil NO3--N retention. Thus, we concluded that long-term
      manure application is beneficial for soil NO3--N content retention, whereas long
      term straw incorporation benefits NO3--N retention.

PMID- 30292119
TI  - Analyses of tetracycline adsorption on alkali-acid modified magnetic biochar:
      Site energy distribution consideration.
AB  - As a widely used antibiotic, tetracycline has a huge hidden danger to human
      health. Municipal sludge rich in organic substances has the potential to produce
      biochar. In this work, the municipal sludge biochar from solid waste was modified
      by the alkali-acid binding method, and tetracycline was efficiently removed from
      the aqueous solution, the adsorption removal efficiency reached to 86% at initial
      concentration of 200 mg/L. The activation energy was determined by analyzing the
      adsorption kinetics at different temperatures and tetracycline concentrations.
      The results showed that tetracycline adsorption on modified biochar was
      endothermic reaction. Presenting the Langmuir-Freundlich model, adsorption site
      energy distributions was reckoned. The average adsorption site energy and
      corresponding standard deviation of the adsorption site energy distribution were
      deduced emphatically to inquiry the strength of tetracycline adsorption on
      modified biochar and the adsorption site heterogeneity. The method proposed of
      research further proves that modified biochar from sewage sludge remove
      tetracycline from contaminated water has great potential, and exploration of
      tetracycline adsorption mechanisms by quantifying average site energy. The
      results and methods of this work can be transferred to study water treatment
      systems.

PMID- 30292120
TI  - Implications of meteorological and physiographical parameters on dengue fever
      occurrences in Delhi.
AB  - Dengue Fever has become an increasing public health concern around the world due
      to its serious health consequences including death, lack of effective vaccine and
      specific treatment. Influence of area specific meteorological and physiographical
      characteristics on the spread of infectious diseases need to be studied to
      understand spatial-temporal aspects of infectious diseases in a particular area.
      Mathematical relationships between various explanatory variables (causative
      factors) and Dengue Fever incidences have been established to quantify and
      prioritize the influence of various factors. So that, effective health care
      services could be provided in these areas. The study successfully explains the
      occurrences of Dengue Fever in Delhi in term of geo-spatial phenomena/variables.
      Meteorological data of 13 stations in Delhi at hourly temporal scale for a period
      2006-2015 have been used along with multi-spectral satellite data. Data on
      reported cases of Dengue Fever on daily basis and for a period of ten years from
      2006 to 2015 have been obtained for Delhi. Python modules have been developed to
      extract values of geospatial parameters and to perform Poisson regression. To
      assess the accuracy of developed Poisson regression based equations, r-squared
      and error statistics have been calculated. Results indicate strong association of
      Dengue Fever incidences with temperature, humidity, wind speed, sunshine hours,
      built-up and vegetation density and distance from dairy locations, waterbodies
      and drainage network. Further, critical ranges of various parameters favouring
      high number of Dengue Fever incidences have been determined. These findings have
      significant public health implications for control and prevention of Dengue Fever
      incidences in Delhi city and surrounding region. Occurrences of Dengue Fever
      incidences are found to be highest in the month of September and October. These
      months represent transition period from rainy season to winter season. It is
      recommended that further study should focus on detailed analysis of causative
      factors in this period.

PMID- 30292121
TI  - Anti-cancer drugs in aquatic environment can cause cancer: Insight about
      mutagenicity in tadpoles.
AB  - Cyclophosphamide (Cyc) and 5-fluorouracil (5-FU) are two of the most used
      antineoplastic drugs (AD) in the world. However, their discharge in the
      environment became a yet-unknown environmental issue that has impact on some
      groups of animals, such as amphibians. We assessed tadpoles (Lithobates
      catesbeianus) exposed to environmental concentrations (EC) of Cyc and 5-FU to
      evaluate whether they can cause morphological and mutagenic changes in them. We
      defined the following groups: control, positive control (50 mg/L of Cyc), EC-Cyc
      I (0.2 MUg/L), EC-Cyc-II (0.5 MUg/L), EF-Cyc (2.0 MUg/L), EC-5-FU-I (13.0 MUg/L),
      EC-5-FU-II (30.4 MUg/L) and EF-5-FU (123.5 MUg/L). EC groups presented predictive
      AD concentrations in 10% and 25% hospital-effluent dilutions in water. EF groups
      met gross hospital-effluent concentrations. Based on our data, ADs caused
      intestinal changes and influenced the interocular distance in tadpoles after 30
      day exposure. We also observed the aneugenic and clastogenic effect of ADs due to
      the higher frequency of micronucleated and binucleated erythrocytes, and blebbed,
      multilobulated, notched and kidney-shaped nuclei in animals exposed to them.
      Based on such changes, we assume that Cyc and 5-FU can trigger malignant cell
      transformation processes, and cancer, in animals exposed to them, even at low
      concentrations. Our study is the first to describe that Cyc and 5-FU, spread in
      the environment, cause damages in non-target organisms opposite to their original
      end.

PMID- 30292122
TI  - Development of physical modelling tools in support of risk scenarios: A new
      framework focused on deep-sea mining.
AB  - Deep-sea mining has gained international interest to provide materials for the
      worldwide industry. European oceans and, particularly, the Portuguese Exclusive
      Economic Zone present a recognized number of areas with polymetallic sulphides
      rich in metals used in high technology developments. A large part of these
      resources are in the vicinity of sensitive ecosystems, where the mineral
      extraction can potentially damage deep-ocean life services. In this context,
      technological research must be intensified, towards the implementation of
      environmental friendly solutions that mitigate the associated impacts. To
      reproduce deep-sea dynamics and evaluate the effects of the mining activities,
      reliable numerical modelling tools should be developed. The present work
      highlights the usefulness of a new framework for risk and impact assessment based
      on oceanographic numerical models to support the adoption of good management
      practices for deep-sea sustainable exploitation. This tool integrates the oceanic
      circulation model ROMS-Agrif with the semi-Lagrangian model ICHTHYOP, allowing
      the representation of deep-sea dynamics and particles trajectories considering
      the sediments physical properties. Numerical simulations for the North Mid
      Atlantic Ridge region, revealed the ability of ROMS-Agrif to simulate real deep
      sea dynamics through validation with in situ data. Results showed a strong
      diversity in the particle residence time, with a dependency on their density and
      size but also on local ocean conditions and bottom topography. The highest
      distances are obtained for the smaller and less dense particles, although they
      tend to be confined by bathymetric constrains and deposited in deepest regions.
      This work highlights the potential of this modelling tool to forecast laden plume
      trajectories, allowing the definition of risk assessment scenarios for deep-sea
      mining activities and the implementation of sustainable exploitation plans.
      Furthermore, the coupling of this numerical solution with models of biota
      inhabiting deep-sea vent fields into ecosystem models is discussed and outlined
      as cost-effective tools for the management of these remote ecosystems.

PMID- 30292123
TI  - Water-quality trends in U.S. rivers, 2002 to 2012: Relations to levels of
      concern.
AB  - Effective management and protection of water resources relies upon understanding
      how water-quality conditions are changing over time. Water-quality trends for
      ammonia, chloride, nitrate, sulfate, total dissolved solids (TDS), total nitrogen
      (TN) and total phosphorus (TP) were assessed at 762 sites located in the
      conterminous United States between 2002 and 2012. Annual mean concentrations at
      the start and end of the trend period were compared to an environmentally
      meaningful level of concern (LOC) to categorize patterns in water-quality
      changes. Trend direction, magnitude, and the proximity of concentrations to LOCs
      were investigated. Of the 1956 site-constituent combinations investigated, 30%
      were above the LOC in 2002, and only six (0.3%) crossed the LOC threshold, either
      from above or below, indicating that waterquality conditions are not
      substantially improving, nor are they degrading, in relation to the LOCs. The
      concentrations of ammonia, nitrate, sulfate, chloride, and TDS tended to be below
      the LOC, and in cases where the trend was increasing (concentrations approached
      the LOC from below), the increases were varied and small in magnitude. In
      contrast, concentrations of TN and TP tended to be above the LOC, and where the
      trend was decreasing (concentrations approached the LOC from above), the
      decreases were larger in magnitude and more consistent. These results indicate
      that if water-quality conditions continue to trend in the same direction, at the
      same rate, for all sites and constituents studied, elevated concentrations are
      more likely to drop below an LOC before low concentrations will exceed an LOC.

PMID- 30292124
TI  - Towards globally customizable ecosystem service models.
AB  - Scientists, stakeholders and decision makers face trade-offs between adopting
      simple or complex approaches when modeling ecosystem services (ES). Complex
      approaches may be time- and data-intensive, making them more challenging to
      implement and difficult to scale, but can produce more accurate and locally
      specific results. In contrast, simple approaches allow for faster assessments but
      may sacrifice accuracy and credibility. The ARtificial Intelligence for Ecosystem
      Services (ARIES) modeling platform has endeavored to provide a spectrum of simple
      to complex ES models that are readily accessible to a broad range of users. In
      this paper, we describe a series of five "Tier 1" ES models that users can run
      anywhere in the world with no user input, while offering the option to easily
      customize models with context-specific data and parameters. This approach enables
      rapid ES quantification, as models are automatically adapted to the application
      context. We provide examples of customized ES assessments at three locations on
      different continents and demonstrate the use of ARIES' spatial multi-criteria
      analysis module, which enables spatial prioritization of ES for different
      beneficiary groups. The models described here use publicly available global- and
      continental-scale data as defaults. Advanced users can modify data input
      requirements, model parameters or entire model structures to capitalize on high
      resolution data and context-specific model formulations. Data and methods
      contributed by the research community become part of a growing knowledge base,
      enabling faster and better ES assessment for users worldwide. By engaging with
      the ES modeling community to further develop and customize these models based on
      user needs, spatiotemporal contexts, and scale(s) of analysis, we aim to cover
      the full arc from simple to complex assessments, minimizing the additional cost
      to the user when increased complexity and accuracy are needed.

PMID- 30292125
TI  - PM2.5 source apportionment for the port city of Thessaloniki, Greece.
AB  - This paper aims to identify the chemical fingerprints of potential PM2.5 sources
      and estimate their contribution to Thessaloniki port-city's air quality. For this
      scope, Positive Matrix Factorization model was applied on a comprehensive PM2.5
      dataset collected over a one-year period, at two sampling sites: the port and the
      city center. The model indicated six and five (groups of) sources contributing to
      particle concentration at the two sites, respectively. Traffic and biomass
      burning (winter months) comprise the major local PM sources for Thessaloniki
      (their combined contribution can exceed 70%), revealing two of the major control
      demanding problems of the city. Shipping and in-port emissions have a non
      negligible impact (average contribution to PM2.5: 9-13%) on both primary and
      secondary particles. Road dust factor presents different profile and contribution
      at the two sites (19.7% at the port; 7.4% at the city center). The secondary
      particle factor represents not only the aerosol transportation over relatively
      long distances, but also a part of traffic-related pollution (14% at the port;
      34% at the city center). The study aims to contribute to the principal role of
      quantitative information on emission sources (source apportionment) in port
      cities for the implementation of the air quality directives and guidelines for
      public health.

PMID- 30292126
TI  - Natural regulatory plasma cells.
AB  - B cells can generate several types of antibody-secreting cells, including
      plasmablasts that divide and are short lived, as well as plasma cells that do not
      proliferate and can persist for extended time periods. Here, we discuss the
      identification of a novel subset of non-dividing plasma cells specialized in the
      production of interleukin(IL)-10. These cells develop at steady state, including
      in germ-free mice, via a mechanism dependent on the B cell receptor for antigen
      and possibly involving the recognition of damaged cells. They are characterized
      by the expression of the inhibitory receptor LAG-3, and also express CD200, PD
      L1, as well as PD-L2. Their specialized epigenome allows them to produce IL-10
      within hours after stimulation, which altogether qualify these cells as natural
      regulatory plasma cells.

PMID- 30292127
TI  - High prevalence of Gammapapillomaviruses (Gamma-PVs) in pre-malignant cutaneous
      lesions of immunocompetent individuals using a new broad-spectrum primer system,
      and identification of HPV210, a novel Gamma-PV type.
AB  - Genus Gammapapillomavirus (Gamma-PV) is the most diverse and largest clade within
      the Papillomaviridae family. A novel set of degenerate primers targeting the E1
      gene was designed and further used in combination with the well-known CUT PCR
      assay to assess HPV prevalence and genus distribution in a variety of cutaneous
      samples from 448 immunocompetent individuals. General HPV, Gamma-PV and mixed
      infections prevalence were significantly higher in actinic keratosis with respect
      to benign and malignant neoplasms, respectively (p = 0.0047, p = 0.0172, p =
      0.00001). Gamma-PVs were significantly more common in actinic keratosis biopsies
      than Beta- and Alpha-PVs (p = 0.002). The full-length genome sequence of a novel
      putative Gamma-PV type was amplified by 'hanging droplet' long-range PCR and
      cloned. The novel virus, designated HPV210, clustered within species Gamma-12.
      This study provides an additional tool enabling detection of HPV infections in
      skin and adds new insights about possible early roles of Gamma-PVs in the
      development of cutaneous malignant lesions.

PMID- 30292128
TI  - Clustered incidence of adult acute promyelocytic leukemia.

PMID- 30292129
TI  - Insight into carbamazepine degradation by UV/monochloramine: Reaction mechanism,
      oxidation products, and DBPs formation.
AB  - UV/monochloramine (NH2Cl) process has attracted some attention for the
      elimination of contaminants of emerging concern as a novel advanced oxidation
      process. However, there is still much uncertainty on the performance and
      mechanisms of UV/NH2Cl process because of its complexity and generation of
      various species of radicals, including NH2*, HO*, Cl* and other reactive chlorine
      species (RCS). The mechanism and influence factors of degradation of
      carbamazepine (CBZ) in the UV/NH2Cl process were investigated, and a synergistic
      effect was observed. Degradation of CBZ under all investigated conditions
      followed pseudo-first order kinetics. The corresponding rate constant increased
      along with the dosage of NH2Cl, and was affected significantly by the presence of
      bicarbonate and natural organic matter. The process has little pH-dependency,
      while the specific contribution of RCS and HO* changed with solution pH, and RCS
      always act as a major contributor to the degradation of CBZ. Eleven byproducts of
      CBZ were identified and their respective evolution profiles were determined. The
      participation of UV in chloramination can reduce the formation of nitrogenous
      DBPs, but promote the formation of carbonaceous DBPs. Furthermore, when influent,
      sand filtered, and granular activated carbon filtered water was respectively used
      as background, degradation of CBZ was inhibited to different degree and more
      disinfection byproducts (DBPs) were generated, compared to deionized water. The
      electrical energy per order for degradation of CBZ in the UV/NH2Cl process was
      also calculated to obtain some preliminary cost information.

PMID- 30292130
TI  - Sustainable production of biomass and biodiesel by acclimation of non-acidophilic
      microalgae to acidic conditions.
AB  - The overwhelming response towards algal biodiesel production has been well
      recognized recently as a sustainable alternative to conventional fuels. Most
      microalgae cannot grow well at acidic pH. The present study, therefore,
      investigated whether non-acidophilic microalgae Desmodesmus sp. MAS1 and
      Heterochlorella sp. MAS3 can be acclimated to extreme-acidic pH for sustainable
      production of biomass and biodiesel. Growth analysis indicated that both the
      microalgal strains possessed a passive uptake of CO2 at pH 3.0 with biomass
      production of 0.25 g dry wt. L-1 in Desmodemus sp. and 0.45 g dry wt. L-1 in
      Heterochlorella sp.. Flow-cytometry analysis for reactive oxygen species,
      membrane permeability and neutral-lipids revealed the capabilities of both
      strains to adapt to the stress imposed by acidic pH. Lipid production was doubled
      in both the strains when grown at pH 3.0. In-situ transesterification of biomass
      resulted in 13-15% FAME yield in the selected microalgae, indicating their great
      potential in biofuel production.

PMID- 30292131
TI  - High-level production of short branched-chain fatty acids from waste materials by
      genetically modified Bacillus licheniformis.
AB  - Short branched-chain fatty acids (SBCFAs) are multi-functional platform chemicals
      used in many fields. Currently, SBCFAs are produced mainly by chemical synthesis,
      which is high cost and lead to environmental pollution. The aim of this study was
      to achieve high-level production of SBCFAs from waste materials, bean dreg and
      crude glycerol. The Bacillus licheniformis DWc9n* was genetically modified by
      overexpression of SBCFAs synthesis genes via replacement of native promoter of
      bkd operon, the mutant strain DWc9n*-PbacA produced 4.68 g/L of SBCFAs,
      increasing by 1.98-fold compared to wild-type strain. SBCFAs concentration was
      further increased to 7.85 g/L through process optimization. In a 5-L batch
      fermenter, the mutant showed SBCFAs production with high concentration (8.37 g/L)
      and productivity (0.20 g/L/h), which is the highest level of SBCFAs production
      based on low-value substrates fermentation. This is the first study describing
      efficient SBCFAs production by the modified B. licheniformis strain from bean
      dreg and crude glycerol.

PMID- 30292133
TI  - Aseptic production of citric and isocitric acid from crude glycerol by
      genetically modified Yarrowia lipolytica.
AB  - The unconventional yeast Yarrowia lipolytica is known for its capacity to produce
      citric or isocitric acid from glycerol. In this study a reduction of production
      cost was achieved by using cheap crude glycerol and conducting the production at
      pH 3 to prevent bacterial contamination. In this study a Y. lipolytica strain
      overexpressing Gut1 and Gut2 was used. For the modified strain, crude glycerol
      proved to be an excellent substrate for production of citric/isocitric acids in
      aseptic conditions, as the final concentration of these compounds reached 75.9 +/
      1.8 g L-1 after 7 days of batch production. Interestingly, the concentration of
      isocitric acid was 42.5 +/- 2.4 g L-1, which is one of the highest concentrations
      of isocitric acid obtained from a waste substrate. In summary, these data show
      that organic acids can be efficiently produced by the yeast Y. lipolytica from
      crude glycerol without any prior purification in aseptic conditions.

PMID- 30292132
TI  - Enhanced performance and hindered membrane fouling for the treatment of coal
      chemical industry wastewater using a novel membrane electro-bioreactor with
      intermittent direct current.
AB  - A membrane electro-bioreactor (MEBR) embracing biological treatment,
      electrokinetic phenomena and membrane filtration was established by applying
      intermittent direct current (DC) to MBR. MEBR exhibited significant improvement
      of treatment performance and reduction of membrane fouling. COD and total phenols
      removal efficiencies increased to 83.53% and 93.28% at an exposure mode of 24'
      OFF/6'-ON, compared to 71.24% and 82.43% in MBR. Trans-membrane pressure
      increment rate declined dramatically in MEBR, which was mainly attributed to the
      increase of sludge floc size and decrease of zeta potential, soluble microbial
      products and specific resistance to filtration, resulted from electrokinetic
      effects such as electrocoagulation, electrophoresis, electroosmosis and
      electromigration of ions. It was notable that DC exposure exerted distinct
      evolution on microbial community, with the improvement of microbial community
      richness and diversity. The relative abundances of functional genera were
      promoted noticeably in MEBR. An interactive relevance existed among microbial
      community structure, mixed liquor properties and operational parameters.

PMID- 30292134
TI  - Reduced nicotinamide adenine dinucleotide phosphate inhibits rat platelet
      aggregation and p38 phosphorylation.
AB  - Previous studies found that reduced nicotinamide adenine dinucleotide phosphate
      (NADPH) protected neurons against ischemia/reperfusion-induced injury. In
      addition to ROS reduction and ATP increment, preliminary data suggested that
      NADPH inhibited ADP and thrombin-induced platelet aggregation. As the effect of
      NADPH on platelet function was not reported by other investigators, the actions
      of NADPH on platelet function and mechanisms of actions were investigated in the
      present study. In vitro studies, the effects of different concentrations of NADPH
      on platelet aggregation induced by ADP (10 MUM), thrombin (0.05 U/mL) or AA (50
      MUM) were determined. The results showed that NADPH could inhibit platelet
      aggregation induced by ADP, thrombin or AA in a concentration dependent manner.
      When the inhibitory effects of NAD+, NADH, NADP+ and NADPH on platelet
      aggregation were compared, NADPH demonstrated the relatively best effect on
      platelet aggregation. In vivo studies, the effects of NADPH on platelet
      aggregation, tail bleeding time, coagulation response and ferric chloride-induced
      thrombosis were determined in mice or rats. The maximum aggregation rate of
      platelets of rats injected with NADPH (5 mg/kg) was lower than platelets from
      control rats. NADPH transiently prolonged tail bleeding time in mice at 30 min
      after the injection of NADPH (7.5 mg/kg), while aspirin (15 mg/kg) significantly
      prolonged the tail bleeding time in mice at all time points examined. NADPH (5
      mg/kg), as well as aspirin (10 mg/kg), had no effect on coagulation response in
      rats. Using a FeCl3-induced abdominal aorta injury thrombosis model,
      administration of NADPH (5 mg/kg) significantly delayed the onset of vessel
      occlusion, while aspirin (10 mg/kg) almost completely prevented the vessel
      occlusion. With microscopic examination the thrombi in injured vessel sections of
      rats received NADPH were much smaller and less dense than that of rats received
      vehicle treatment. ADP induced an increase in phosphorylation of p38 and the
      effect was markedly inhibited by the p38 inhibitor SB203580. Similarly, NADPH
      also inhibited ADP-induced phosphorylation of p38. Similar to NADPH, SB203580
      robustly inhibited ADP- and thrombin-induced platelet aggregation. In addition,
      NADPH also reduced ADP-induced increases in ROS in platelets. The current results
      demonstrated that NADPH inhibited platelet aggregation, oxidative stress and p38
      phosphorylation, suggesting that NADPH might be a novel compound for management
      of high risk of cardiovascular disease.

PMID- 30292135
TI  - Differences in the ease with which mutant viruses escape from human monoclonal
      antibodies against the HA stem of influenza A virus.
AB  - BACKGROUND: Broadly protective human monoclonal antibodies that recognize the
      conserved epitopes in the HA of influenza A virus are being developed as
      therapeutic agents. Emergence of resistant viruses must always be considered when
      developing therapeutic agents against influenza. OBJECTIVES: We examined human
      hetero-reactive mAbs against the HA stem of influenza A virus for the ease with
      which escape mutant viruses emerged. STUDY DESIGN: We attempted to generate the
      mutant viruses escaped from the hetero-reactive anti-HA stem antibodies. We also
      evaluated their protective efficacy, binding affinity, and epitopes. RESULTS: We
      obtained several human monoclonal antibodies (mAbs) that react with the HA of
      different HA subtypes of influenza A virus belonging to group 1. Upon attempting
      to generate escape mutant viruses, we found that the ease with which such viruses
      emerged differed among the mAbs; viruses barely escaped from two of the mAbs
      (clones S9-3-37 and F20C77), whereas escape from the third mAb (clone F5B7)
      occurred readily. Comparisons of the mAbs revealed that the HA stem epitopes, in
      vitro neutralization potency, binding affinity to H1-HA, and protective efficacy
      against lethal challenge with H1N1pdm09 virus were all comparable. CONCLUSIONS:
      These results demonstrate the importance of determining the ease with which
      escape mutant viruses emerge when evaluating anti-HA stem antibodies as antiviral
      agents during preclinical testing.

PMID- 30292136
TI  - Simultaneous determination of seven flavonoids, two phenolic acids and two
      cholesterines in Tanreqing injection by UHPLC-MS/MS.
AB  - A new ultra-high performance liquid chromatography combined with triple
      quadrupole mass spectrometry was developed to evaluate the quality of Tanreqing
      injection. Seven flavonoids (Rutin, Baicalin, Scutellarin, Chrysin-7-O-Beta-d
      glucoronide, Oroxylin A-7-O-beta-d-glucoronide, Wogonin, Luteolin-7-O-glucoside),
      two phenolic acids (Chlorogenic acid, Caffeic acid) and two cholesterines
      (Ursodeoxycholic acid, Chenodeoxycholic acid) in Tanreqing injection could be
      measured simultaneously. For the determination of the eleven compounds, the
      conditions were set as follows: The mobile phase was a gradient of 0.1% aqueous
      formic acid solution (A) and acetonitrile (B); the flow rate was 0.2 mL min-1,
      the column was Acquity UPLC HSS T3 column (2.1 mm * 100 mm, 1.8 MUm); and the
      multiple-reaction monitoring (MRM) with a negative electro spray ionization
      interface (ESI-) was selected. Within the test ranges, all the standard
      regression curves showed excellent linear regression (r > 0.99). In terms of
      (relative standard deviation) RSDs, the precision, repeatability and stability of
      the eleven compounds were all lower than 3%. The recovery rates of Tanreqing
      injection and the RSD were 97.8-103.7% and 0.4%-2.0%, respectively. The RSD value
      was in accordance with the requirements of less than 3.0%. This method has been
      successfully used in the analysis of Tanreqing injection. In summary, a fast,
      accurate and reliable UPLC-ESI--MS/MS method was successfully developed for the
      simultaneous detection of the eleven major active ingredients with different
      chemical structures in Tanreqing injection, and can be used for the quality
      control of Tanreqing injection as well.

PMID- 30292137
TI  - Global lower limb muscle coactivation during walking at different speeds:
      Relationship between spatio-temporal, kinematic, kinetic, and energetic
      parameters.
AB  - Muscle coactivation is the mechanism that regulates the simultaneous activity of
      antagonist muscles around the same joint. During walking, muscle joint
      coactivation varies within the gait cycle according to the functional role of the
      lower limb joints. In the present study, we used a time-varying multi-muscle
      coactivation function (TMCf) with the aim of investigating the coactivation of 12
      lower limb muscles and its relationship with the gait cycle, gait speed (low,
      self-selected, and fast), ground reaction force, gait variability, and mechanical
      energy consumption, and recovery in a sample of 20 healthy subjects. Results show
      that the TMCf is speed dependent and highly repeatable within and between
      subjects, similar to the vertical force profile, and negatively correlated with
      energy recovery and positively correlated with both energy consumption and
      balance-related gait parameters. These findings suggest that the global lower
      limb coactivation behavior could be a useful measure of the motor control
      strategy, limb stiffness, postural stability, energy efficiency optimization, and
      several aspects in pathological conditions.

PMID- 30292139
TI  - A Novel Aurora-A Inhibitor (MLN8237) Synergistically Enhances the Antitumor
      Activity of Sorafenib in Hepatocellular Carcinoma.
AB  - Currently, sorafenib-based therapy is the standard treatment for advanced
      hepatocellular carcinoma (HCC), and there is a strong rationale for investigating
      its use in combination with other agents to achieve better therapeutic effects.
      Aurora-A, a member of a family of mitotic serine/threonine kinases, is frequently
      overexpressed in human cancers and therefore represents a target for therapy.
      Here, we investigated a novel Aurora-A inhibitor, MLN8237, together with
      sorafenib in HCC cells in vitro and in vivo, and elucidated the possible
      molecular mechanism. Here, it was found that MLN8237 was strongly synergistic
      with sorafenib in inhibition of HCC progression by altering cell growth, cell
      cycle regulation, apoptosis, migration, invasion, and angiogenesis. Mechanism
      dissection suggests that the combination of MLN8237 and sorafenib led to
      significant inhibition of the activation of phospho-Akt (p-Akt) and phospho-p38
      mitogen-activated protein kinase (p-p38 MAPK) and their downstream genes
      including CDK4, cyclinD1, and VEGFA. The activators of p-Akt and p-p38 MAPK
      signaling partially reversed the synergistic inhibitory effects of sorafenib and
      MLN8237 on HCC progression. Subsequent in vivo studies further confirmed the
      synergistic effects of sorafenib and MLN8237. Collectively, the newly developed
      sorafenib-MLN8237 combination may be a novel therapy to better inhibit HCC
      progression.

PMID- 30292140
TI  - Metformin Protects against H2O2-Induced Cardiomyocyte Injury by Inhibiting the
      miR-1a-3p/GRP94 Pathway.
AB  - Ischemia-reperfusion (I/R) injury is a major side effect of the reperfusion
      treatment of the ischemic heart. Few therapies are available for the effective
      prevention of this injury caused by the oxidative stress-induced cardiomyocyte
      apoptosis. Metformin was shown to have a potential cardiac protective effect and
      ability to reduce cardiac events, but the exact mechanism remains unclear. Here,
      we aimed to confirm and investigate the mechanisms underlying potential metformin
      activity against I/R injury in response to oxidative stress. We determined that
      the expression of miR-1a-3p was significantly increased in neonatal rat
      ventricular cells (NRVCs), which were exposed to H2O2in vitro and in the hearts
      of mice that underwent the I/R injury. MiR-1a-3p was shown to target the 3' UTR
      of GRP94, which results in the accumulation of un- or misfolded proteins, leading
      to the endoplasmic reticulum (ER) stress. The obtained results demonstrated that
      C/EBP beta directly induces the upregulation of miR-1a-3p by binding to its
      promoter. Furthermore, as a direct allosteric AMPK activator, metformin was shown
      to activate AMPK and significantly reduce C/EBP beta and miR-1a-3p levels
      compared with those in the control group. In conclusion, metformin protects
      cardiomyocytes against H2O2 damage through the AMPK/C/EBP beta/miR-1a-3p/GRP94
      pathway, which indicates that metformin may be applied for the treatment of I/R
      injury.

PMID- 30292138
TI  - Oligonucleotide Aptamer-Mediated Precision Therapy of Hematological Malignancies.
AB  - Precision medicine has recently emerged as a promising strategy for cancer
      therapy because it not only specifically targets cancer cells but it also does
      not have adverse effects on normal cells. Oligonucleotide aptamers are a class of
      small molecule ligands that can specifically bind to their targets on cell
      surfaces with high affinity. Aptamers have great potential in precision cancer
      therapy due to their unique physical, chemical, and biological properties.
      Therefore, aptamer technology has been widely investigated for biomedical and
      clinical applications. This review focuses on the potential applications of
      aptamer technology as a new tool for precision treatment of hematological
      malignancies, including leukemia, lymphoma, and multiple myeloma.

PMID- 30292141
TI  - Exon Skipping in a Dysf-Missense Mutant Mouse Model.
AB  - Limb girdle muscular dystrophy 2B (LGMD2B) is without treatment and caused by
      mutations in the dysferlin gene (DYSF). One-third is missense mutations leading
      to dysferlin aggregation and amyloid formation, in addition to defects in
      sarcolemmal repair and progressive muscle wasting. Dysferlin-null mouse models do
      not allow study of the consequences of missense mutations. We generated a new
      mouse model (MMex38) carrying a missense mutation in exon 38 in analogy to a
      clinically relevant human DYSF variant (DYSF p.Leu1341Pro). The targeted mutation
      induces all characteristics of missense mutant dysferlinopathy, including a
      progressive dystrophic pattern, amyloid formation, and defects in membrane
      repair. We chose U7 small nuclear RNA (snRNA)-based splice switching to
      demonstrate a possible exon-skipping strategy in this new animal model. We show
      that Dysf exons 37 and 38 can successfully be skipped in vivo. Overall, the
      MMex38 mouse model provides an ideal tool for preclinical development of
      treatment strategies for dysferlinopathy.

PMID- 30292142
TI  - The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology
      (FRACTION) program: innovative, high-throughput clinical screening of
      immunotherapies.
AB  - BACKGROUND: The unprecedented success of immuno-oncology (I-O) agents targeting
      the cytotoxic T lymphocyte-associated antigen 4 and programmed death-1/programmed
      death-ligand 1 pathways has stimulated the rapid development of other I-O agents
      against novel immune targets. Bristol-Myers Squibb has designed a novel phase II
      platform trial, the Fast Real-time Assessment of Combination Therapies in Immuno
      ONcology (FRACTION) Program, to efficiently identify promising combinations for
      patients with specific malignancies. The concept and study design of the FRACTION
      Program-currently ongoing in patients with advanced non-small-cell lung cancer
      (FRACTION-Lung), gastric cancer (FRACTION-Gastric Cancer) and renal cell
      carcinoma (FRACTION-RCC)-are described. METHODS: The FRACTION Program comprises
      open-label, phase II studies that use adaptive randomisation designs with rolling
      combination regimens. Master Protocols provide the overall study design
      framework, whereas Sub-Protocols introduced over time provide details on specific
      I-O combination therapies to which patients may be randomised. In a Master
      Protocol, patients are enrolled into different Study Tracks based on
      characteristics such as prior I-O therapy experience. Patients who progress may
      be rerandomised to other combination regimens from any ongoing Sub-Protocol.
      Primary objectives are to assess objective response rate, median duration of
      response and progression-free survival rate at 24 weeks; the secondary objective
      is to investigate safety and tolerability. Biomarker collection before and on
      treatment will facilitate identification of patient subsets who benefit most from
      each therapy. CONCLUSIONS: The FRACTION Program allows for the evaluation of
      multiple I-O combinations through individual studies for specific tumours using
      an adaptive trial design and continuous enrolment.

PMID- 30292143
TI  - Predictors of urinary antibiotics in children of Shanghai and health risk
      assessment.
AB  - BACKGROUND: An extensive exposure to antibiotics has been confirmed in children,
      but the predictors and potential health risk remain unclear. OBJECTIVE: To
      investigate the predictors of antibiotics in urine and potential health risk in
      children of Shanghai. METHODS: We selected 284 school children aged 8-11 years
      from a central area of Shanghai, China, in 2017. Ultra-performance liquid
      chromatography coupled with high-resolution mass spectrometry was used to measure
      20 antibiotics, including four human antibiotics (HAs), six veterinary
      antibiotics (VAs), 10 human/veterinary antibiotics (H/VAs), and three metabolites
      in first morning urine. Logistic regression model was used to examine the
      associations of 17 variables related to demographic and socioeconomic factors,
      recent antibiotic use, drinking water intake, food consumption, and
      anthropometric measurements with the detection frequency of HAs, VAs, or H/VAs in
      urine. After daily intake was estimated, health risk was assessed for VAs and
      H/VAs by using hazard quotient (HQ) and hazard index (HI) based on
      microbiological or toxicological effects. RESULTS: The detection frequencies of
      20 antibiotics and three metabolites ranged from 0 to 27.8% with an overall
      detection frequency being 56.0%. The detection frequency of HAs increased with
      age and screen time at weekend. Sex, age, family income and screen time were
      positively associated with the detection frequencies of VAs and H/VAs. Children
      reporting antibiotic use in the past three months had a higher detection
      frequency of HAs. Children with a higher consumption frequency of dairy products
      had a higher detection frequency of VAs + H/VAs, but a lower detection frequency
      of HAs. An increased overall detection frequency of all antibiotics was seen in
      children with higher consumption frequencies of aquatic products, livestock and
      poultry meat, or milk and dairy products. HQ >1 was only found for ciprofloxacin
      (5.6%) and ofloxacin (0.4%) based on microbiological effect. HI >1 was found in
      6.0% of children for microbiological effect and none was found for toxicological
      effect. CONCLUSIONS: Predictors for antibiotics in urine for children included
      sex, age, family income, screen time, clinical use, and animal-derived food
      consumption. There was potential health risk for children with exposure to
      antibiotics.

PMID- 30292145
TI  - Chiral pharmaceuticals: Environment sources, potential human health impacts,
      remediation technologies and future perspective.
AB  - Chiral pharmaceuticals (CPs), including non-steroid anti-inflammatory drugs
      (NSAIDs), beta-blockers and some herbicide and pesticides, are widely used in
      aquaculture, clinical treatment and many other fields. However, people are
      increasingly concerned about such ubiquitous pollutants, which can frequently be
      detected in contaminated soil and water. In large part, the significant sources
      of chiral pharmaceuticals stem from industrial processes, such as the direct
      discharge of untreated or incompletely treated wastewaters containing chiral
      pharmaceuticals, incorrect storage and use, animal wastes and biosolids. The main
      ways for human exposure to chiral pharmaceuticals are the disease treatment
      process and chiral pharmaceuticals contaminants. According to the results of a
      series of toxic studies, some diseases, even cancers, may be associated with
      exposure to certain chiral pharmaceuticals. Therefore, the treatment of chiral
      pharmaceuticals has become an important issue. The current advanced remediation
      techniques for chiral pharmaceuticals include the conventional method (sorption
      and sonolysis), biotransformation (an aerobic granular sludge-sequencing batch
      reactor and constructed wetland system) and advanced oxidation processes
      (ozonation and photocatalysis). Herein, in this review, we summarize the current
      status and sources of chiral pharmaceuticals, potential effects on human health,
      as well as the superiority, disadvantages and prospects of current advanced
      remediation technologies. Moreover, we also anticipate the prospect of the future
      research needed for chiral pharmaceuticals pollutant remediation.

PMID- 30292144
TI  - Mortality burden attributable to PM1 in Zhejiang province, China.
AB  - BACKGROUND: Limited evidence is available on the health effects of particulate
      matter with an aerodynamic diameter of <1 MUm (PM1), mainly due to the lack of
      its ground measurement worldwide. OBJECTIVES: To identify and examine the
      mortality risks and mortality burdens associated with PM1, PM2.5, and PM10 in
      Zhejiang province, China. METHODS: We collected daily data regarding all-cause
      (stratified by age and gender), cardiovascular, stroke, respiratory, and chronic
      obstructive pulmonary disease (COPD) mortality, and PM1, PM2.5, and PM10, from 11
      cities in Zhejiang province, China during 2013 and 2017. We used a quasi-Poisson
      regression model to estimate city-specific associations between mortality and PM
      concentrations. Then we used a random-effect meta-analysis to pool the provincial
      estimates. To show the mortality burdens of PM1, PM2.5, and PM10, we calculated
      the mortality fractions and deaths attributable to these PMs. RESULTS: Daily
      concentrations of PM1, PM2.5, and PM10 ranged between 0-199 MUg/m3, 0-218 MUg/m3,
      and 0-254 MUg/m3, respectively; Mortality effects were significant in lag 0-2
      days. The relative risks for all-cause mortality were 1.0064 (95% CI: 1.0034,
      1.0094), 1.0061 (95% CI: 1.0034, 1.0089), and 1.0060 (95% CI: 1.0038, 1.0083)
      associated with a 10 MUg/m3 increase in PM1, PM2.5, and PM10, respectively. Age-
      and gender-stratified analysis shows that elderly people (aged 65+) and females
      are more sensitive to PMs. The mortality fractions of all-cause mortality were
      estimated to be 2.39% (95% CI: 1.28, 3.48) attributable to PM1, 2.53% (95% CI:
      1.42, 3.63) attributable to PM2.5, and 3.08% (95% CI: 1.95, 4.19) attributable to
      PM10. The ratios of attributable cause-specific deaths for PM1/PM2.5, PM1/PM10,
      and PM2.5/PM10 were higher than the ratios of their respective concentrations.
      CONCLUSIONS: PM1, PM2.5 and PM10 are risk factors of all-cause, cardiovascular,
      stroke, respiratory, and COPD mortality. PM1 accounts for the vast majority of
      short-term PM2.5- and PM10-induced mortality. Our analyses support the notion
      that smaller size fractions of PM have a more toxic mortality impacts, which
      suggests to develop strategies to prevent and control PM1 in China, such as to
      foster strict regulations for automobile and industrial emissions.

PMID- 30292146
TI  - Executive dysfunctions and behavioral changes in early drug-naive patients with
      Parkinson's disease.
AB  - OBJECTIVES: This study aims to explore the clinical profiles and onset age
      related difference of executive dysfunctions and behavioral changes in early drug
      naive patients with Parkinson's disease (PD). METHODS: A cross-sectional analysis
      on 419 early stage drug-naive PD patients was conducted. The frontal assessment
      battery (FAB) was used to assess executive functions and the frontal behavioral
      inventory (FBI) was used to assess behavioral changes. RESULTS: Executive
      dysfunctions were detected in 113 patients (27.0%), and 219 patients (52.3%)
      displayed varied degrees of behavioral changes. The most frequent affected domain
      for the FAB was lexical fluency (31.7%), while the three most frequent affected
      domains for the FBI were apathy (26.0%), irritability (24.3%) and inattention
      (20.8%). Compared to the early-onset PD (EOPD) patients, the late-onset PD (LOPD)
      patients exhibited significantly higher frequent damage in FAB especially
      similarities, motor series, and conflicting instructions as well as lower
      frequent damage in lexical fluency. The frequencies of FBI-abnormal were not
      different between the two groups. Multivariate analyses indicated that age at PD
      onset was independently associated with FAB total score and its subscores
      including lexical fluency, motor series, conflicting instructions and go-no go
      task, but it has no relationship with FBI total score and its subscores.
      CONCLUSIONS: Executive deficits and behavioral changes are common in the early
      stage of PD. Age at PD onset is independently associated with the performance of
      executive functions. However, behavioral changes in PD may be not affected by
      onset age.

PMID- 30292148
TI  - Cortical biometals: Changed levels in suicide and with mood disorders.
AB  - BACKGROUND: Changes in levels of metals have been suggested to contribute to the
      pathophysiologies of several neurodegenerative disorders but to our knowledge
      this is the first metallomic study in CNS from patients with mood disorders. The
      focus of this study was on cortical regions affected by the pathophysiologies of
      bipolar disorders and major depressive disorders. METHODS: Levels of metals were
      measured using inductively coupled plasma mass spectrometry in Brodmann's areas
      (BA) 6, 10 and 17 from patients with major depressive disorders (n = 13), bipolar
      disorders (n = 12) and age / sex matched controls (n = 13). RESULTS: There were
      lower levels of cortical strontium (BA 6 & 10), ruthenium (BA 6 & 17) and cadmium
      (BA 10) from patients with major depressive disorder as well as lower levels of
      strontium in BA 10 from patients with bipolar disorders. Unexpectedly, there were
      changes in levels of 16 metals in the cortex, mainly BA 6, from suicide
      completers compared to those who died of other causes. LIMITATIONS: Cohort sizes
      were relatively small but comparable with many studies using human postmortem
      CNS. Like all studies on non-treatment naive patients, drug treatment was a
      potential confound in our experiments. CONCLUSIONS: Our exploratory study
      suggests changes in levels of metals in bipolar disorders and major depressive
      disorders could be affecting cortical oxidative balance in patients with mood
      disorders. Our data raises the possibility that measuring levels of specific
      biometals in the blood could be used as a biomarker for increased risk of
      suicide.

PMID- 30292147
TI  - Symptoms of social anxiety disorder and major depressive disorder: A network
      perspective.
AB  - BACKGROUND: We used network analyses to examine symptoms that may play a role in
      the co-occurrence of social anxiety disorder (SAD) and major depressive disorder
      (MDD). Whereas latent variable models examine relations among latent constructs,
      network analyses have the advantage of characterizing direct relations among the
      symptoms themselves. METHOD: We conducted network modeling on symptoms of social
      anxiety and depression in a clinical sample of 130 women who met criteria for
      SAD, MDD, both disorders, or had no lifetime history of mental illness. RESULTS:
      In the resulting network, the core symptoms of social fear and depressed mood
      appeared at opposite ends of the network and were weakly related; so-called
      "bridges" between these symptoms appeared to occur via intervening variables. In
      particular, the worthless variable appeared to play a central role in the
      network. LIMITATIONS: Because our data were cross-sectional, we are unable to
      draw conclusions about the direction of these effects or whether these variables
      are related to each other prospectively. CONCLUSIONS: Continued testing of these
      pathways using longitudinal data will help facilitate the development of more
      effective clinical interventions for these disorders.

PMID- 30292149
TI  - Portable and selective colorimetric film and digital image colorimetry for
      detection of iron.
AB  - Iron is an important trace element in environmental and biological systems, the
      development of simple and selective methods for the determination of iron is
      important. In this work, completely biodegradable tapioca starch was introduced
      as the substrate to entrap standard chromogenic probes (1,10-phenanthroline) for
      fabrication of a novel colorimetric sensor for ferrous. A clear plasticized thin
      film from tapioca starch was fabricated inside a small plastic tube as a portable
      test kit. A red complex was obtained by exposing the film to a ferrous solution,
      while no color changes were obtained with various other ions, indicating
      excellent selectivity. The developed films were applied in conjunction with a
      digital image colorimetry for quantification of ferrous. Calculated molecular
      absorption of the red complex showed the widest linear range (0 to 10 mg L-1)
      with good linearity (R2 < 0.9934) with ferrous concentrations. The developed
      method provided good inter-day precision (1.75 to 3.97%RSD, 5 days 15 sensors),
      good accuracy (+2.35% to +4.57% relative error), and low detection limit (0.09 +/
      0.01 mg L-1). The concentrations of ferrous ion in soil and water samples
      quantified by the developed method were not significantly different from atomic
      absorption spectrophotometry at 95% confidence level. The films were stable for
      at least three months.

PMID- 30292150
TI  - Investigations over optical properties of boron complexes of benzothiazolines.
AB  - Quantum chemical analyses over benzothiazolines and their boron complexes are
      performed. In calculations, M06-2X method was selected with 6-31 + G(d,p) level.
      Structural and spectral (IR and NMR) characterization of studied compounds are
      done in detail. Quantum chemical descriptors (QCDs) are calculated to investigate
      the optical properties. Furthermore, molecular electrostatic potential (MEP) maps
      of the studied compounds are calculated by using electro-static potential (ESP)
      charges. According to QCDs and MEP maps, NLO properties of boron complexes are
      more than those of benzothiazolines and (Z)-2-((pyridin-2-ylmethylene)amino)
      benzenethiolatebutane-1,3-bis(olate)boron(III), complex (7), has the most NLO
      activity in studied compounds. Finally, solvent effect on NLO activity are
      investigated by calculating UV-vis spectrum in gas phase (epsilon = 1), toluene
      (epsilon = 2.3741), chloroform (epsilon = 4.7113), methanol (epsilon = 32.613),
      water (epsilon = 78.3553) and n-methylformamide-mixture (epsilon = 181.56).
      According to these spectra results, NLO activity mainly increases with increasing
      of polarizability of media.

PMID- 30292151
TI  - Optical spectroscopic properties recorded for simple BOPHY dyes in condensed
      media: The mirror-symmetry factor.
AB  - The BOPHY structural scaffold provides opportunities for the synthesis of
      innumerable derivatives with linear geometries and well-controlled pi-conjugation
      pathways. The simpler BOPHY chromophores are highly fluorescent but exhibit poor
      mirror symmetry between absorption and fluorescence spectra at ambient
      temperature. In particular, the absorption (and excitation) spectra are broad and
      appear as two overlapping bands of comparable intensity. In constrained media,
      such as low-temperature rigid glasses or stretched poly(ethylene) films, mirror
      symmetry is restored. Analysis of the temperature dependence recorded for simple
      BOPHY derivatives indicates that the vibronic envelope accompanying the
      electronic transitions can be well described in terms of low- and medium
      frequency modes. Whereas the fluorescence spectral profile is only weakly
      dependent on temperature, the excitation spectrum is far more affected. The
      magnitude of the low-frequency mode, and the associated electron-phonon coupling,
      increase substantially with increasing temperature and is responsible for
      temperature broadening and distortion of the excitation spectrum in solution.
      This critical low-frequency vibronic mode is associated with out-of-plane
      torsional bending of the BOPHY unit. Variable temperature NMR studies failed to
      provide unequivocal evidence for conformational changes of one of the derivatives
      over the temperature range 193-353 K.

PMID- 30292152
TI  - Chalcogens doped BaTiO3 for visible light photocatalytic hydrogen production from
      water splitting.
AB  - The pristine BaTiO3 has been experimentally confirmed to catalyze hydrogen
      production from water splitting, but the reaction cannot be driven by the visible
      light because of the wide energy band gap of BaTiO3. To understand the
      feasibility of the reaction driven by the visible light of the strongest part of
      the solar energy, we have investigated the effect of different concentrations of
      oxygen group element dopants on the electronic and optical properties of BaTiO3
      by using first-principles density functional theory calculations with meta-GGA +
      MBJ potential. The formation energy of each doped structure is calculated to
      examine the feasibility of synthesis in energy. The energy band gaps and the
      energy positions of conduction and valence bands are calculated and the results
      reveal that all the structures except the one that doped with 5 at% Te satisfy
      the conditions of water splitting although the energy band gaps of the doped
      BaTiO3 decrease obviously. The partial charge distributions of conduct band
      maximum and valence band minimum are used to demonstrate the electron-hole
      separation. The absorption coefficients are calculated for all the considered
      structures. The results demonstrate that the doped chalcogens can significantly
      enhance the absorption in visible light range, which implies that the doped
      BaTiO3 are promising to catalyze the hydrogen production from water splitting
      driven by solar energy.

PMID- 30292153
TI  - Growing practices and the use of potentially harmful chemical additives among a
      sample of small-scale cannabis growers in three countries.
AB  - BACKGROUND: With the growth of legal cannabis markets there has been recognition
      of the adverse impacts of certain cannabis growing practices, notably, use of
      harmful chemicals. A major concern has been the use of Plant Growth Regulators
      (PGRs) which limit plant size and stimulate bud production. These chemicals, many
      of which have been banned from food crops, have been found unlisted in cannabis
      growing nutrients sold online or in hydroponic stores. This study describes the
      cannabis growing practices used by small-scale recreational cannabis growers and
      specifically their self-reported use of chemicals. METHODS: Web survey data from
      1722 current and recent cannabis growers in Australia, Denmark, and the UK, who
      were asked about their cannabis growing practices, including the use of
      fertilizers and supplements. RESULTS: Overall 44% of the sample reported using
      any chemical fertilizers, supplements or insecticides. Logistic regression
      indicated that the unique predictor of the use of chemicals was growing
      hydroponically. CONCLUSION: Problems associated with product labeling and
      uncertainty regarding product constituents made it difficult for growers and the
      researchers to determine which products likely contained PGRs or other harmful
      chemicals. There is a need for further research to analyze constituents of
      chemical products marketed to cannabis growers.

PMID- 30292154
TI  - Pollution status of marine protected areas worldwide and the consequent toxic
      effects are unknown.
AB  - Chemical pollution is considered a factor that may threaten marine protected
      areas (MPAs), and recent studies have found contamination and associated
      biological effects in some MPAs. However, organized data on this topic are
      lacking. This study reviewed the literature on pollution in MPAs in order to
      compile data, determine whether MPAs are influenced by pollution and, whenever
      possible, describe how they are being affected by contaminants. The results show
      that the pollution status is unknown in most MPAs worldwide. When any information
      is available, it is often insufficient to diagnose the threats to biodiversity or
      to support further actions. More robust and extensive information is available on
      a small number of MPAs, and much less information is available regarding the
      negative effects of pollution. More than 80% of the areas studied exhibited
      evidence of contamination at potentially toxic concentrations or were found to
      have a status that produced toxic effects on the biota. The scientific community
      is encouraged to study pollution in MPAs worldwide.

PMID- 30292155
TI  - Short- and medium-chain chlorinated paraffins in sediments from the Laizhou Bay
      area, North China: Implications for transportation from rivers to marine
      environment.
AB  - The concentrations of short- and medium-chain chlorinated paraffins (SCCPs and
      MCCPs) were measured for riverine and marine sediments from the Laizhou Bay area
      in order to investigate their spatial distributions, possible sources and
      transport behaviors. Concentrations of SCCPs and MCCPs in riverine sediments
      varied from 8.4 to 2000 ng g-1 dw and from 1.8 to 3200 ng g-1 dw, respectively.
      Higher concentrations were found exclusively at industrial sites. Emissions from
      local factories were the main source of CPs in river sediments of this region. It
      was 5-22 ng g-1 dw and 6-63 ng g-1 dw with an average value of 11 ng g-1 dw and 9
      ng g-1 dw for SCCPs and MCCPs in marine sediments of Laizhou Bay, respectively.
      In addition to riverine input, ship related emissions are suggested to be another
      important source of CPs in the Laizhou Bay. MCCPs/SCCPs values and compositional
      profiles of SCCPs were found to vary along with CP concentrations. A distinct
      shift to congener groups with shorter carbon chains and lower chlorination from
      emission sources to remote areas was noticed. The role of log octanol-water
      partition coefficient (LogKow) values indicated decisive in their transportation
      from emission sources to remote areas in the Laizhou Bay area.

PMID- 30292156
TI  - Interactive effects of contamination and trematode infection in cockles
      biochemical performance.
AB  - Anthropogenic activities, especially those involving substances that pollute the
      environment can interfere with bivalve populations, as well as parasitism, a
      fundamental ecological interaction often neglected. In marine environments,
      organisms are concomitantly exposed to pollutants and parasites, a combination
      with synergistic, antagonistic or additive effects representing a potential
      threat to aquatic communities sustainability. In the present study, Cerastoderma
      edule (the edible cockle)-Himasthla elongata (trematode) was used as host
      parasite model. Cockles are worldwide recognized as good sentinel and
      bioindicator species and can be infected by several trematodes, the most abundant
      macroparasites in coastal waters. Tested hypotheses were: 1) cockles exposed to
      increasing parasite pressure will present greater stress response; 2) cockles
      exposure to arsenic (single concentration test: 5.2 MUg L-1) will change parasite
      infection success and cockles stress response to infection. Arsenic was used for
      being one of the most common pollutants in the world and stress response assessed
      using biochemical markers of glycogen content, metabolism, antioxidant activity
      and cellular damage. Results showed that intensity of parasite pressure was
      positively correlated to biochemical response, mainly represented by higher
      metabolic requirements. Contamination did not affect parasite infection success.
      Compared to arsenic, trematode infection alone exerted a stronger impact: higher
      glycogen storage, metabolism and cellular damage and antioxidant activity
      inhibition. In interaction, parasitism and arsenic reduced hosts metabolism and
      cellular damage. Therefore, to a certain extent and in a contamination scenario,
      cockles may benefit from trematode infection, working as a protection for the
      pollutant accumulation in the organisms, reducing overall ROS production, which
      can consequently led to less toxic effects. These findings highlighted the
      deleterious effects of trematode infection in their hosts and showed the
      importance of including parasitology in ecotoxicological studies.

PMID- 30292157
TI  - What are the effects of soil treatment procedures (sterilization by gamma
      irradiation and solvent-assisted spiking) on DDE bioaccumulation by earthworms?
AB  - Ionizing gamma-irradiation and solvent-assisted spiking are frequently applied to
      eliminate microbial activity and to induce hydrophobic organic compounds (HOCs)
      into soil, respectively, when studying the accumulation of chemicals in
      terrestrial organisms. However, the side-effects that may arise from these
      treatments on soil-HOC interaction and, subsequently, the kinetics and extents of
      bioaccumulation are not thoroughly understood. To this end, the accumulation of
      1,1-dichloro-2,2-bis(p-chlorophenyl)etylene (p,p'-DDE) by Eisenia andrei was
      studied in sterilized or unsterilized and freshly spiked (FS) or historically
      contaminated (HC) soils in parallel with an analysis of aliphatic and hydrophilic
      soil organic matter (SOM) moieties using mid-infrared diffuse reflectance
      spectroscopy (DRIFT-S). Irradiation did not impart significant changes on
      spectral SOM descriptors. In contrast, earthworm inhabitation increased the
      relative presence of aliphatic moieties to a greater extent than hydrophilic
      ones, reaching or exceeding pre-treatment levels. Overall, effects on SOM
      chemistry can be ranked as earthworms > spiking > irradiation. Corresponding
      changes at the bioaccumulation level were observed for the FS soil (i.e., a 27%
      reduction in bioaccumulation upon sterilization) but not for the HC soil. This
      implies that in contrast to the interactions between aged p,p'-DDE and sterilized
      HC soil, the interactions established between freshly added p,p'-DDE and
      sterilized FS soil were altered by gamma-irradiation-induced secondary effects
      alone or in combination with earthworm inhabitation. Thus, although the soil
      treatment processes studied here should not drastically impact compound
      bioaccumulation, they should be considered in mechanistic studies where the
      qualitative and quantitative aspects of compound-soil (organic matter)-earthworm
      interactions are at the centre of attention.

PMID- 30292158
TI  - Uptake and transformation of steroid estrogens as emerging contaminants influence
      plant development.
AB  - Steroid estrogens are emerging contaminants of concern due to their devastating
      effects on reproduction and development in animals and humans at very low
      concentrations. The increasing steroid estrogen in the environment all over the
      world contrasts very few studies for potential impacts on plant development as a
      result of estrogen uptake. This study evaluated the uptake, transformation and
      effects of estradiol (17beta-E2) and ethinyl estradiol (EE2) (0.1-1000 MUg L-1)
      on lettuce. Uptake increased in leaves and roots in a dose-dependent manner, and
      roots were the major organ in which most of the estrogen was deposited. The
      transformation of estrogens to major metabolite and their further reverse
      biotransformation in lettuce tissue was identified. At low concentrations (0.1
      and 50 MUg L-1) estrogens resulted in enhanced photosynthetic pigments, root
      growth and shoot biomass. Application of higher concentrations of estrogens (10
      mg L-1) significantly reduced total root growth and development. This was
      accompanied by increased levels of hydrogen peroxide (H2O2), and malondialdehyde
      (MDA), and activities of antioxidant enzymes superoxide dismutase (SOD),
      peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX). Taken together,
      these findings suggest that at low concentrations estrogens may biostimulate
      growth and primary metabolism of lettuce, while at elevated levels they have
      adverse effects.

PMID- 30292159
TI  - Comparison of greenhouse and open field cultivations across China: Soil
      characteristics, contamination and microbial diversity.
AB  - A national scale survey was conducted to determine an array of inorganic and
      organic contaminants in agricultural soils from two cultivation modes (greenhouse
      vs. open field) in 20 provinces across China. The investigated contaminants
      include organochlorine pesticides (OCPs), phthalate esters (PAEs), polycyclic
      aromatic hydrocarbons (PAHs), lead (Pb), zinc (Zn), copper (Cu) and cadmium (Cd).
      The large amounts of agrochemicals used and special cultivation mode in
      greenhouse caused substantial soil pollution and deterioration of soil quality.
      Mean concentrations of both OCPs and PAEs in greenhouse soil were approximately
      100% higher than those in open field. The pH values were 6.85 +/- 1.04 and 7.34
      +/- 0.84 for greenhouse and open field, respectively (p > 0.05). The soil
      microbial community was predicted to be affected by pollution in greenhouse
      through the PICRUSt analysis of 16s rRNA sequences. The 12 variables including
      various chemicals and soil properties together explained 15% of the observed
      variation in the community composition. In the studied variables, PAEs and lead
      were the primary factors affecting microbial diversity in greenhouse soils, while
      pH had the greatest impact on the microbial community in open field soils. These
      findings enhanced our understanding of the environmental impact and contamination
      management of greenhouses worldwide.

PMID- 30292160
TI  - Two-generational reproductive toxicity assessment of 6:2 chlorinated
      polyfluorinated ether sulfonate (F-53B, a novel alternative to perfluorooctane
      sulfonate) in zebrafish.
AB  - As an alternative to perfluorooctane sulfonate (PFOS), 6:2 chlorinated
      polyfluorinated ether sulfonate (commercial name: F-53B) has been used in the
      Chinese chrome plating industry for over four decades. It has been increasingly
      detected in environmental matrices in recent years, causing great concern
      regarding its potential health risks to humans and wildlife. However, its adverse
      effects on biota remain largely unknown. To explore the chronic toxicity of F-53B
      on reproduction, a two-generational study was conducted using zebrafish (Danio
      rerio). Adult zebrafish (F0 generation) were chronically exposed to different
      concentrations of F-53B (0, 5, 50, and 500 MUg/L) for 180 d using a flow-through
      exposure system, with F1 and F2 generations reared without exposure. The
      reproductive toxicity endpoints were assessed in F0 and F1 adult fish. Results
      showed that F-53B accumulated in the F0 gonads and transferred to the F1
      generation via maternal eggs, and even remained in F1 adult fish and their eggs
      (F2) after 180 d depuration. In the F0 generation, F-53B exposure significantly
      inhibited growth and induced reproductive toxicity, including decreased
      gonadosomatic index and egg production/female, changes in the histological
      structure of the gonads, and increased serum testosterone levels. In particular,
      serum estradiol and vitellogenin levels were significantly increased in 5 MUg/L F
      53B-exposed adult males. The transcriptional levels of several genes along the
      hypothalamic-pituitary-gonadal axis were altered in F0 generation fish. Testis
      transcriptome analysis revealed that F-53B exposure disrupted spermatogenesis in
      F0 male zebrafish. Maternal transfer of F-53B also induced adverse effects on
      growth and reproduction in the F1 generation. Furthermore, the higher occurrence
      of malformation and lower survival in F1 and F2 embryos indicated that parental
      exposure to F-53B could impair the embryonic development of offspring. Taken
      together, this study demonstrated that F-53B could induce reproductive toxicity
      in zebrafish similar to that induced by legacy PFOS, and its potential adverse
      effects on offspring deserve further investigation.

PMID- 30292161
TI  - Morpho-physiological and proteomic responses of Aegilops tauschii to imposed
      moisture stress.
AB  - Moisture stress is the most important limitation of wheat production in the
      worldwide. Among the tribe Triticeae, Aegilops tauschii is one of the most
      valuable gene sources of resistance to abiotic stresses. In order to identify the
      most tolerant accession to moisture stress, and to understand its adaptive
      mechanisms at the molecular level, the present experiment was carried out on ten
      Ae. tauschii accessions under normal (95% soil pot capacity) and moisture stress
      (45% soil pot capacity) conditions. At the start of the heading time, the
      expanded flag leaves of treated and untreated plants were sampled for two
      dimensional electrophoresis (2-DE) based on proteomics approach. A19 accession
      was less affected by the imposed moisture stress; therefore, it was used for the
      proteomics experiment. Among 252 protein spots which were reproducibly detected
      in each given 2-DE gels, 25 spots showed significant differences between the two
      moisture treatments; 17 spots were upregulated and 8 spots were downregulated.
      The identified proteins by MALDI-TOF/TOF, were allocated to seven functional
      protein groups, which were mainly involved in photosynthesis/respiration (28.5%),
      carbohydrate metabolism (14.2%), energy metabolism (7.1%), chaperone (14.2%),
      protein translation and processing (14.2%), repair and stability of the genome
      (7.1%) and unknown function (14.2%). We report this for the first time that RMI2
      protein (in the group of repair and stability of the genome) was significantly
      changed in wheat in response to moisture stress. We believe that, the identified
      proteins could play important roles in acclimation and tolerance to moisture
      stress and provide the genetic pathways for improving tolerance to moisture
      stress in wheat.

PMID- 30292162
TI  - Interaction of high seawater temperature and light intensity on photosynthetic
      electron transport of eelgrass (Zostera marina L.).
AB  - The interaction of widely recognized causes of eelgrass decline (high seawater
      temperature and limited light intensity) on photosynthetic electron transport was
      investigated via chlorophyll fluorescence technique. High seawater temperature
      combined light intensity significantly increasing the relative maximum electron
      transport rate (rETRmax); at critical temperature of 30  degrees C, the rETRmax
      increased with the enhancement of light intensity, indicating the elevation of
      overall photosynthetic performance. Based on the magnitude of effect size (eta2),
      light intensity was the predominant factor affecting the performance index
      (PIABS), indicating that photosystem II (PSII) was sensitive to light intensity.
      Moreover, the donor side was severely damaged as evidenced by the higher decrease
      amplitude of fast component and its subsequent incomplete recovery. The reaction
      center exhibited limited flexibility due to the slight decrease amplitude in
      maximum photochemical quantum yield. In contrast with PSII, photosystem I (PSI)
      was more sensitive to high seawater temperature, based on the magnitude of eta2
      derived from the maximal decrease in slope. High seawater temperature
      significantly increased PSI activity, plastoquinol reoxidation capacity, and
      probability for electron transfer to final PSI electron acceptors. Moreover, it
      combined elevated light intensity significantly stimulated the activity of cyclic
      electron flow (CEF) around PSI. Higher activity of both PSI and CEF contributed
      to balancing the linear electron transport via alleviating the over-reduction of
      the plastoquinone pool, exhibiting flexible regulation of photosynthetic electron
      transport at critical temperature. Therefore, limited light intensity decreased
      the tolerance of eelgrass to critical temperature, which might be a factor
      contributing factor in the observed decline.

PMID- 30292163
TI  - Bio-priming mitigates detrimental effects of salinity on maize improving
      antioxidant defense and preserving photosynthetic efficiency.
AB  - Salinity is an abiotic stress which seriously affects crop production over the
      world, particularly in arid and semi-arid regions, with harmful effects on
      germination, growth and yield. Maize (Zea mays L.), cultivated in a wide spectrum
      of soil and climatic conditions, is the third most important cereal crop after
      rice and wheat, moderately sensitive to salt stress. A saline level more than 250
      mM NaCl damages maize plants, causing severe wilting. In this study, the effects
      of hydro-priming (distilled water) and bio-priming (Rosmarinus officinalis L. and
      Artemisia L. leaf extracts) on seed germination and seedling growth of maize,
      under 100 mM NaCl salinity were investigated. The factorial experiments were
      carried out in greenhouse under controlled condition (25  degrees C in 12/12 h
      day/night) based on a completely randomized design with three replicates. Results
      showed that both hydro- and bio-priming increased germination percentage and
      germination indexes in maize seeds. Rosmarinus extract was the most effective in
      inducing salt resistance in 30 days old seedlings, with beneficial effects in the
      strengthening of the antioxidant system and in the maintenance of a higher
      photosynthetic efficiency under salt stress condition.

PMID- 30292164
TI  - The relationship between exclusive breastfeeding and infant development: A 6- and
      12-month follow-up study.
AB  - BACKGROUND: Breastfeeding offers several advantages for infants with research
      suggesting that it benefits development, including cognitive and language
      development. However, limited research has examined the benefits in infants under
      one year. AIMS: To investigate the association between breastfeeding duration and
      infant development. STUDY DESIGN: A longitudinal study conducted over 12 months.
      SUBJECTS: Two hundred fifty-five mothers and their infants living in South Korea
      were seen at three time-points based on infants' age (4, 6, and 12 months).
      OUTCOME MEASURES: Breastfeeding data were collected at 4 and 6 months. The Korea
      Developmental Screening Test for Infants & Children was administered at 6 and 12
      months to measure developmental milestones. We analyzed the relationship between
      breastfeeding duration in the first 6 months and infant development at 6 and 12
      months using logistic regression analysis. RESULTS: Compared to infants who did
      not breastfeed at all, infants who were exclusively breastfed until 4 months of
      age followed by mixed breastfeeding had a better communication and social
      interaction at 6 months, and better cognition, communication, and social
      interaction at 12 months. Exclusive breastfeeding until 6 months of age had no
      apparent impact on the outcomes at 6 and 12 months. CONCLUSIONS: Exclusive
      breastfeeding up to 4 months of age followed by mixed breastfeeding might
      maximize the effects of infant development in their first year after birth.
      Breastfeeding programs should effectively communicate that exclusive
      breastfeeding for at least 4 months benefits infant development.

PMID- 30292165
TI  - Perspectives of vaccinators on the factors affecting uptake of meningococcal ACWY
      vaccine amongst school leavers in London.
AB  - OBJECTIVES: Uptake of meningococcal ACWY (Men ACWY) vaccine amongst school
      leavers is suboptimal in London (9.9% compared to 17.4% nationally in 2015/16).
      This study explores service delivery barriers and elicits insights from general
      practice staff on their interaction with this cohort. The purpose was to inform
      the National Health Service England (London) public health commissioning team's
      strategy to improve Men ACWY vaccination uptake in London. STUDY DESIGN:
      Qualitative semi-structured interviews study. METHODS: Purposive sampling of
      practice nurses from three general practices from each of the three London
      clinical commissioning group areas (Barnet, Camden and Newham) with the largest
      numbers of 18-20 year old registered patients. Participants were recruited
      through their practice managers. A thematic analysis approach was used. RESULTS:
      A total of ten interviews were conducted between June and August 2017. Five
      themes were identified: (1) Nurses unsupported by practice systems; (2)
      difficulty getting school leavers into the practice; (3) confused messaging; (4)
      reliance on parental responsibility for health; and (5) perception of complacency
      amongst adolescents. CONCLUSION: Little is known about the service factors that
      impede uptake of adolescent vaccinations. This exploratory study suggests that
      existing programmatic mechanisms for delivering the Men ACWY catch-up programme
      were not adequate. The number of adolescent vaccinations offered has increased in
      the UK in the last five years and is likely to continue. Although the findings
      need to be further extrapolated in quantitative research, general practice staff
      need more systematic guidance on their role and how they can support vaccine
      decision-making in later adolescence.

PMID- 30292167
TI  - Biochar derived from swine manure digestate and applied on the removals of heavy
      metals and antibiotics.
AB  - Swine manure digestate (SMD) is rich of functional groups. In this work, raw
      biochar (BC) was prepared from SMD by oxygen-limiting pyrolysis, and HCl-BC, NH3
      BC and Mn-BC were obtained by modifying BC with HCl, NH3.H2O and KMnO4. The
      modified biochar was negatively charged and showed a larger specific surface area
      and total pore volume, and higher contents of Si-O-Si and O-H bonds and aromatic
      rings with CO bond. Among them, Mn-BC, was given a new Mn-O group. The adsorption
      capacities of biochar were determined using a model aqueous solution containing
      some metals and antibiotics. The adsorption experiment results showed that Mn-BC
      had a quite good capacity for Cu and Zn removal. And the removal efficiency of As
      (III), sulfadimidine and tylosin of 83.98%, 83.76%, and 77.34% respectively, was
      also observed by using Mn-BC. Mn-BC was considered to be a promising material for
      the adsorption of heavy metals and antibiotics.

PMID- 30292166
TI  - Proton therapy for low-grade gliomas in adults: A systematic review.
AB  - For adult patients with diffuse low-grade glioma (LGG) proton therapy is an
      emerging radiotherapy modality. The number of proton facilities is rapidly
      increasing. However, there is a shortage of published data concerning the
      clinical effectiveness compared to photon radiotherapy and potential proton
      specific toxicity. This study aimed to systematically review and summarize the
      relevant literature on proton therapy for adult LGG patients, including
      dosimetric comparisons, the type and frequency of acute and long-term toxicity
      and the clinical effectiveness. A systematic search was performed in several
      medical databases and 601 articles were screened for relevance. Nine articles
      were deemed eligible for in-depth analysis using a standardized data collection
      form by two independent researchers. Proton treatment plans compared favorably to
      photon-plans regarding dose to uninvolved neural tissue. Fatigue (27-100%),
      alopecia (37-85%), local erythema (78-85%) and headache (27-75%) were among the
      most common acute toxicities. One study reported no significant long-term
      cognitive impairments. Limited data was available on long-term survival. One
      study reported a 5-year overall survival of 84% and 5-year progression-free
      survival of 40%. We conclude that published data from clinical studies using
      proton therapy for adults with LGG are scarce. As the technique becomes more
      available, controlled clinical studies are urgently warranted to determine if the
      potential benefits based on comparative treatment planning translate into
      clinical benefits.

PMID- 30292168
TI  - The role of the secondary phloem during the development of the grapevine Berry
      Shrivel ripening disorder.
AB  - Berry Shrivel (BS) is a post-veraison physiological ripening disorder of
      grapevine berries. Its symptoms encompass low pH, reduced content of sugars and
      anthocyanins, and loss of turgor leading to berries shriveling. Evidence for the
      primary causes of BS is still speculative and anatomical studies are scarce. So
      far, anatomical studies have determined necrotic cells, degraded primary phloem
      cells and hardening of secondary phloem cells in the rachis of BS affected
      grapes. The picture is far from being complete. Herein we report in-depth
      analyses of the ultrastructure, anatomy and spatial elementary analysis of rachis
      and pedicel tissues of BS symptomatic grape clusters with different symptom
      severity. We hypothesize that structural changes in the vascular system of BS
      affected grape clusters could alter transport functions of the phloem tissue and
      contribute to the appearance of BS symptoms. By applying different microscopic
      techniques (LM, SEM, TEM and EDS) we found a number of anatomical differences in
      both, rachis and pedicels, between H and BS symptomatic grapes, which include:
      (i) extended areas of collapsed cells and cell wall thickenings in the secondary
      phloem in BS samples; (ii) reduced number of cell layers in the cambium in BS
      samples; (iii) higher rate of callose deposition on sieve plates that are
      additionally covered with a carbohydrate-like material in BS samples; and (iv)
      reduced (up to 60%) estimated sieve tube conductivity in BS samples.

PMID- 30292170
TI  - Computer simulation for the study of the liquid chromatographic separation of
      explosive molecules.
AB  - The application of high performance liquid chromatography (HPLC) to separate
      explosive chemicals was investigated by molecular dynamics (MD) simulations. The
      explosive ingredients including NG, RDX, HMX and TNT were assigned as solutes,
      while methanol (CH3OH) and acetonitrile (CH3CN) were assigned as solvents in the
      solution system. The polymeric-molecular siloxanes (SiC8) and poly-1,2
      methylenedioxy-4-propenyl benzene (PISAF) compounds were treated as stationary
      phase in the simulation. The simulation results showed that the different species
      of explosive ingredients were separated successfully in the solutions by each of
      the constructed stationary phase of SiC8 and PISAF after a total simulation time
      of 12.0 ps approximately, which were consistent with the experimental analysis of
      HPLC spectra. The origin for the separation was found due to the electrostatic
      interactions between polymer and explosives.

PMID- 30292169
TI  - Anisotropic composite material phantom to improve skeletal muscle
      characterization using magnetic resonance elastography.
AB  - The presence and progression of neuromuscular pathology, including spasticity,
      Duchenne's muscular dystrophy and hyperthyroidism, has been correlated with
      changes in the intrinsic mechanical properties of skeletal muscle tissue. Tools
      for noninvasively measuring and monitoring these properties, such as Magnetic
      Resonance Elastography (MRE), could benefit basic research into understanding
      neuromuscular pathologies, as well as translational research to develop
      therapies, by providing a means of assessing and tracking their efficacy. Dynamic
      elastography methods for noninvasive measurement of tissue mechanical properties
      have been under development for nearly three decades. Much of the technological
      development to date, for both Ultrasound (US)-based and Magnetic Resonance
      Imaging (MRI)-based strategies, has been grounded in assumptions of local
      homogeneity and isotropy. Striated skeletal and cardiac muscle, as well as brain
      white matter and soft tissue in some other organ regions, exhibit a fibrous
      microstructure which entails heterogeneity and anisotropic response; as one seeks
      to improve the accuracy and resolution in mechanical property assessment,
      heterogeneity and anisotropy need to be accounted for in order to optimize both
      the dynamic elastography experimental protocol and the interpretation of the
      measurements. Advances in elastography methodology at every step have been aided
      by the use of tissue-mimicking phantoms. The aim of the present study was to
      develop and characterize a heterogeneous composite phantom design with uniform
      controllable anisotropic properties meant to be comparable to the frequency
      dependent anisotropic properties of skeletal muscle. MRE experiments and
      computational finite element (FE) studies were conducted on a novel 3D-printed
      composite phantom design. The displacement maps obtained from simulation and
      experiment show the same elliptical shaped wavefronts elongated in the plane
      where the structure presents higher shear modulus. The model exhibits a degree of
      anisotropy in line with literature data from skeletal muscle tissue MRE
      experiments. FE simulations of the MRE experiments provide insight into proper
      interpretation of experimental measurements, and help to quantify the importance
      of heterogeneity in the anisotropic material at different scales.

PMID- 30292171
TI  - A Potent and Selective ULK1 Inhibitor Suppresses Autophagy and Sensitizes Cancer
      Cells to Nutrient Stress.
AB  - In response to stress, cancer cells generate nutrients and energy through a
      cellular recycling process called autophagy, which can promote survival and tumor
      progression. Accordingly, autophagy inhibition has emerged as a potential cancer
      treatment strategy. Inhibitors targeting ULK1, an essential and early autophagy
      regulator, have provided proof of concept for targeting this kinase to inhibit
      autophagy; however, these are limited individually in their potency, selectivity,
      or cellular activity. In this study, we report two small molecule ULK1
      inhibitors, ULK-100 and ULK-101, and establish superior potency and selectivity
      over a noteworthy published inhibitor. Moreover, we show that ULK-101 suppresses
      autophagy induction and autophagic flux in response to different stimuli.
      Finally, we use ULK-101 to demonstrate that ULK1 inhibition sensitizes KRAS
      mutant lung cancer cells to nutrient stress. ULK-101 represents a powerful
      molecular tool to study the role of autophagy in cancer cells and to evaluate the
      therapeutic potential of autophagy inhibition.

PMID- 30292172
TI  - Brain injury and adverse outcomes: a contemporary review of the evidence.
AB  - Recently, research focusing on the implications of brain injuries for deleterious
      outcomes spanning a wide range of developmental domains has flourished. Findings
      from this literature suggest that brain injury is a potent source of risk for
      negative outcomes including neurodegenerative diseases, cognitive impairment,
      behavioral problems, and psychiatric diagnoses. Despite this evidence, few
      studies have examined the extent to which these findings represent a causal
      relationship. This review outlines the expansive literature in this developing
      area and provides a discussion of potential threats to internal validity.
      Finally, suggestions for future research are provided with a particular emphasis
      on leveraging existing findings to better understand the role of brain injury in
      the development of deleterious outcomes.

PMID- 30292174
TI  - A Mystery of Patent Ductus Arteriosus and Serum Osmolality in Preterm Infants.
AB  - OBJECTIVE:  Patent ductus arteriosus (PDA) is an important clinical problem
      associated with mortality and serious morbidities. It is thought that serum
      osmolality may affect ductal patency. We aimed to investigate the importance of
      serum osmolality related to ductal patency in preterm infants. STUDY DESIGN:  Our
      study was conducted between January 2013 and December 2017. Premature infants,
      birth weight <1,500 g and gestational age <32 weeks were included in the study.
      Serum osmolality was compared between infants with hemodynamically significant
      PDA (hsPDA) and non-hsPDA. RESULTS:  During the study period, 799 patients were
      evaluated. Mean serum osmolality levels were higher in the "hsPDA" group (297 +/-
      10.9 vs. 292 +/- 8.3 mOsm/L) (p = 0.001). The area under the curve for osmolality
      was 0.582 (p = 0.0006, 95% confidence interval: 0.541-0.622) at the time of
      diagnosis for predicting hsPDA, with a cutoff value for osmolality of 300 mOsm/L.
      CONCLUSION:  Serum osmolality may be recognized as an important contributing
      factor for ductal patency especially among extremely preterm infants who are most
      likely to have hsPDA in the early days of life.

PMID- 30292173
TI  - Matched-Pair Analysis of Local Infiltration Analgesia in Total Knee Arthroplasty:
      Patient Satisfaction and Perioperative Pain Management in 846 Cases.
AB  - In the recent past, numerous studies evaluating local infiltration analgesia
      (LIA) with controversial results have been reported. Efforts have been made to
      improve patients' outcome regarding operation techniques and material, as well as
      pain management and anesthetic methods. In this study, postoperative pain
      management and patient satisfaction were evaluated in patients undergoing total
      knee replacement surgery with or without intraoperative LIA. Within the context
      of the "Quality Improvement in Postoperative Pain Management" (QUIPS) project,
      parameters were collected on the first postoperative day. All patients included
      in this study underwent primary knee replacement surgery with general anesthesia.
      Parameters were compared after performing a 1:1 matched-pair analysis within 14
      orthopaedic departments. Pain levels and pain management satisfaction were
      measured using the numerous rating scales, and pain medication use was compared.
      From 2010 to 2015, 2,789 patients who underwent primary knee arthroplasty with
      general anesthesia were evaluated within the project, of whom a total of 846
      patients could be compared after performing a matched-pair analysis. Pain scores
      were significantly better in the LIA group (p = 0.019 for activity pain, p =
      0.043 for maximum pain, p < 0.001 for minimum pain), but pain management
      satisfaction was not superior (p = 0.083). Patients with LIA required less
      opioids in the recovery room (p = 0.048), while nonopioid medication did not
      differ significantly (p = 0.603). At the ward, 24 hours postoperatively, no
      significant difference in the use for nonopioids (p = 0.789) could be measured,
      whereas patients in the LIA group received significantly more opioids (p <
      0.001). Although LIA achieved improvement in pain score outcome, and a comparable
      patient satisfaction level in the immediate postoperative course, the use of LIA
      in knee arthroplasty, controversially discussed in the current literature, was
      not able to reduce the need for opioid pain medication in this study.

PMID- 30292175
TI  - The Association between Maternal Height, Body Mass Index, and Perinatal Outcomes.
AB  - OBJECTIVE:  To test the hypothesis that maternal height is associated with
      adverse perinatal outcomes, controlling for and stratified by maternal body mass
      index (BMI). STUDY DESIGN:  This was a retrospective cohort study of all births
      in California between 2007 and 2010 (n = 1,775,984). Maternal height was
      categorized into quintiles, with lowest quintile (<=20%) representing shorter
      stature and the uppermost quintile (>=80%) representing taller stature. Outcomes
      included gestational diabetes mellitus (GDM), preeclampsia, cesarean, preterm
      birth (PTB), macrosomia, and low birth weight (LBW). We calculated height/outcome
      associations among BMI categories, and BMI/outcome associations among height
      categories, using various multivariable logistic regression models. RESULTS: 
      Taller women were less likely to have GDM, nulliparous cesarean, PTB, and LBW;
      these associations were similar across maternal BMI categories and persisted
      after multivariable adjustment. In contrast, when stratified by maternal height,
      the associations between maternal BMI and birth outcomes varied by specific
      outcomes, for example, the association between morbid obesity (compared with
      normal or overweight) and the risk of GDM was weaker among shorter women
      (adjusted odds ratio [aOR], 95% confidence interval [CI]: 3.48, 3.28-3.69) than
      taller women (aOR, 95% CI: 4.42, 4.19-4.66). CONCLUSION:  Maternal height is
      strongly associated with altered perinatal risk even after accounting for
      variations in complications by BMI.

PMID- 30292176
TI  - Effects of sulfide and polysulfides transmitted by direct or signal transduction
      mediated activation of TRPA1 channels.
AB  - Hydrogen sulfide (H2 S) is a gaseous mediator in various physiological and
      pathological processes, including neuroimmune modulation, metabolic pathways,
      cardiovascular system, tumour growth, inflammation and pain. Now the hydrogen
      polysulfides (H2 Sn ) have been recognised as signalling molecules modulating ion
      channels, transcription factors and protein kinases. Transient receptor potential
      (TRP) cation channels can be activated by mechanical, thermal or chemical
      triggers. Here, we review the current literature regarding the biological actions
      of sulfide and polysulfide compounds mediated by TRP channels with special
      emphasis on the role of TRPA1, best known as ion channels in nociceptors.
      However, the non-neuronal TRPA1 channels should also be considered to play
      regulatory roles. Although sulfide and polysulfide effects in different
      pathological circumstances and TRPA1-mediated processes have been investigated
      intensively, our review attempts to present the first comprehensive overview of
      the potential crosstalk between TRPA1 channels and sulfide-activated signalling
      pathways.

PMID- 30292177
TI  - [Plasma Mass Spectrometry of Sea Mountain Basalts in the Western Pacific and Its
      Geological Significance].
AB  - As a kind of spectroscopic technique, the remote laser-induced breakdown
      spectroscopy (Remote LIBS) can qualitatively or quantitatively measure the
      elemental compositions of remote targets with high-power laser and focusing
      optical path. In this work, a Remote LIBS system was designed and established to
      probe the target from 2 to 10 meters. It is characterized with Cassegrain
      telescope structure and automatic focusing technique. Based on this system, a
      method to remotely retrieve the major elemental abundance of rocks is presented.
      With comparative experiment, the influences on spectral signal by pulse laser
      energy, acquisition delay time, integration time, accumulative pulse number are
      analyzed to find out the optimum parameters: the wavelength of laser is 1 064 nm,
      pulse energy is 120 mJ, delay time is 1.5 MUs, integration time is 1 ms,  and
      each spectrum data acquired with averaging 30 times detection. 48 pieces of rock
      specimens and 6 kinds of standard rock samples (shale, granite, andesite, basalt,
      gneiss and pegmatite) are selected for the experiment. As to the atomic spectra
      database, 8 characteristic spectral lines of the major elements (SiI390.55
      nm,AlI394.40 nm,AlI396.15 nm, Ca II 396.85 nm,FeI404.6
      nm,SiI500.60nm,MgI518.36nm,NaI589.59 nm) were extracted for analyses. Then a PLS
      model is constructed to quantitatively analyze the rock elements. 48 rock
      specimens were selected as the training sets to serve the model. The 6 standard
      samples were used to test the solved model. The testing results shows that the
      elemental abundance of Si and Al can be predicted accurately with average
      relative error of only 9.4% and 9.6% respectively.

PMID- 30292178
TI  - [Plasma Mass Spectrometry of Sea Mountain Basalts in the Western Pacific and Its
      Geological Significance].
AB  - Seamount basalts recorded important information of seamount and deep evolution
      process. Through the analysis of petrology and REE geochemical characteristics of
      Govorov Guyot, Niulang Guyot, Arnold Guyot, Skornyakova Guyot, Gordin Guyot,
      McDonnell Guyot, Lingyi Seamount, Xufu Seamounts basalts in the western Pacific,
      it shows that basalts in study area have amygdaloidal, fumarolic-amygdaloidal and
      porphyritic texture. Rocks are mainly composed of phenocrysts and matrix. Mineral
      composition of phenocrysts is mainly plagioclase, olivine and clinopyroxene.
      Mineral composition of matrix is plagioclase, olivine, clinopyroxene and glassy
      etc. REE patterns and parameters of each sea mountain basalts reflect the typical
      characteristics of oceanic island basalts. It indicates that the seamount in
      study area is a typical volcanic seamount in plate caused by multiple hotspots.
      At the same time, it may have been influenced by multi-stage fault and magmatic
      activity.

PMID- 30292179
TI  - [Determination of Impurity Elements in Rosin with Inductively Coupled Plasma Mass
      Spectrometry].
AB  - An analytical method for the content determining of impurity elements in rosin
      was established. After being dissolved and diluted in ethanol, the rosin was
      analyzed directly with inductively coupled plasma mass spectrometry (ICP-MS).
      Some experiment conditions were optimized, such as the RF power, carrier gas
      flow, sample amount, and increase the temperature of plasma center channel, to
      improve the ionization efficiency. Proper oxygen concentration was added in
      plasma to make sure organic carbon been complete burned, resulting in carbon
      deposits eliminate and signal stable. Though equipment turn and isotopes
      selection can effectively eliminate interferences caused by oxide and doubly
      charged ions mass spectrums. A large amount of isobars and polyatomic ion
      interference were avoided. The collision reaction cell (CRC) technology was used
      to further eliminate the mass spectra interference, with He collision model and
      H2 reaction model, respectively. The results showed that detection limits of
      different impurity elements were within the range from 0.002 to 0.035 MUg.g-1,
      and the recoveries of real added sample were between the range from 94.00% to
      106.00%, and relative standard deviation is less than 3.34%. This method enables
      to detect rosin dissolved in ethanol directly and needs no special sample
      preparation equipment. This simple, fast and accurate approach provides us a new
      analysis method for the quality valuation of impurity elements in rosin.

PMID- 30292180
TI  - [X-Ray Fluorescence Intensity Calculation for Micro-Particles via MCNPX and WDXRF
      Experiment].
AB  - In order to research the effect of X-ray fluorescence (XRF) analysis on the
      results in the sample's micro particles, MCNPX models had been established for an
      X-ray fluorescence analyzer in this paper. It had studied the characteristics of
      the samples with different particle sizes, the fluorescence peak counts, the peak
      to total ratios and the peak to source ratios. A micro particle analysis
      experiment had been designed for its verification. The results showed that: as
      for the relationship between the fluorescence intensity and the particle sizes,
      the MCNPX calculations were consistent with the theoretical, but contrary with
      the experimental results; the reason is that some hypotheses about samples in the
      MCNPX models were contrary with the actual states; the samples were crushed by
      grinding to small particles and tableting process, the MCNPX calculations and
      experimental results can be conversion; when the particle sizes of the samples
      reached the certain sizes, the fluorescence peak counts, the peak to total ratios
      and the peak to source ratios were stable value; within a particular size range,
      the influence of the particle size effects cannot be ignored, otherwise this
      influence can be ignored. The research methods and conclusions in this paper can
      provide a technical reference guide for X-ray analysis in practices.

PMID- 30292181
TI  - [Development and Output Characteristics of 785 nm Portable Grating-Coupled
      External Cavity Tunable Semiconductor Laser].
AB  - Aiming at the miniaturization requirement of shifted excitation Raman
      spectroscopy test system, a portable grating-coupled external cavity (EC) tunable
      semiconductor laser in Littrow configuration is designed and fabricated with a
      commercial 785 nm high-power laser diode as the gain device. By using a new
      wavelength tuning method, aiming to change the position of gain device relative
      to the collimating lens in the horizontal direction, a miniaturized device with
      the size of 140 mm*65 mm*50 mm is designed. Compared to the traditional
      wavelength tuning method which is to change the light incident angle by rotating
      the diffraction grating, this new tuning method reduces the translational
      distance of semiconductor gain device effectively, thus it is conductive to the
      fast and broad wavelength tuning of portable EC laser. The experimental results
      show that the EC laser has a wide wavelength tuning range. Under any injection
      current from 340 to 900 mA, a wavelength tuning range of more than 10 nm can be
      realized. Especially at 900 mA, good performance including a 11.67 nm-wavelength
      tuning range from 779.40 to 791.07 nm, a less than 0.2 nm-spectral linewidth, an
      up to 280 mW-output power, and a more than 25 dB-amplified spontaneous emission
      suppression ratio is presented, which fully meets the basic testing requirements
      of shifted excitation Raman spectroscopy. Moreover, 1.35 nm-electric wavelength
      tuning range is achieved by applying a mini-piezoelectric actuator. This
      indicates that the home-made 785 nm portable grating-coupled EC tunable
      semiconductor laser is suitable as the light source of portable shifted
      excitation Raman spectroscopy testing system to eliminate the fluorescence
      background of Raman spectrum.

PMID- 30292182
TI  - Discrimination of GMOs Using Terahertz Spectroscopy and CS-SVM.
AB  - This paper develops an effective identification method to discriminate
      genetically modified (GM) and non-GM organisms. The method is proposed based on
      terahertz (THz) spectroscopy and support vector machines optimized by Cuckoo
      Search algorithm (CS-SVM). In this study, the THz spectra of three GM and non-GM
      soya seed samples were obtained by using terahertz time-domain spectroscopy (THz
      TDS) system between 0.2 and 1.2 THz. Then, the SVM model is employed to
      distinguish GM and non-GM soya seeds, in which the two crucial parameters,
      including the penalty factor and kernel parameter, are optimized by CS algorithm.
      The experimental results show that THz spectroscopy combined with CS-SVM can
      provide a rapid, reliable and non-invasive method for GMOs and non-GMOs
      discrimination.

PMID- 30292183
TI  - Direct Evidences of Shallow Donor Level Enhanced Green Emission in ZnO Quantum
      Dots.
AB  - ZnO Quantum dots with particle sizes about 5 nm were prepared by sol-gel method,
      the research about the photo luminescence(PL)/photoluminescence excitation(PLE)
      spectrum and the fluorescence lifetime indicated that the green emissions can be
      divided into two parts which were attributed to different transit mechanisms. The
      higher energy green emission was due to the electrons transit from conduction
      band to oxygen vacancies while the lower energy green emission was assigned to
      the electrons transit from the shallow donor levels which enhanced the green
      emission to the oxygen vacancies and the shallow donor levels was also the reason
      why the green emission reach strongest intensity when the excitation energy was a
      little lower than the band gap energy. While the blue emission can be explained
      by the electrons transiting from Zinc intervals to the valence band. The two
      mechanisms of green emission are first highlighted and should be considered in
      the optical application.

PMID- 30292184
TI  - Effect of the Nitrogen Incorporation on the Microstructure and Photoelectric
      Properties of N Type Nanocrystalline Silicon Thin Films.
AB  - N type silicon-rich nanocrystalline-SiN(x) ? H films were prepared by plasma
      enhanced chemical vapor deposition technique by changing NH3 flow rate. The
      effect of nitrogen incorporation on the microstructure and photoelectric
      properties of the thin films were characterized by Raman, Fourier transform
      infrared spectroscopy, ultraviolet-visible absorption spectra, and Hall effect
      measurement. The results indicated that with the increasing NH3, a phase
      transition from microcrystalline to amorphous silicon occured. Transmission
      electron microscope observation revealed that the size of silicon quantum dots
      could be adjusted by varying the flow rate of NH3. The microstructure order of
      the films reduced with increasing the flow rate of NH3, while the optical band
      gap increased, and the optical band tail became narrow. Meanwhile, Si-N bonds
      density increased and P doping was blocked. I-V testing results showed that with
      increasing NH3, the conductivity of films first decreased compared with
      nanocrystalline-Si and then increased. These behaviors reveal a competition in
      the mechanisms controlling the conductivity. However, with further increasing
      NH3, the conductivity decreased significantly due to rapid carrier recombination
      on the amorphous net structure.

PMID- 30292185
TI  - Preparation and Properties of Novel Polymer Blue Fluorescent Materials.
AB  - The pyrazoline was chosen as the luminescent functional group, and then four
      kinds of new polyamide polymer blue fluorescent materials were designed and
      synthesized. The structures of them were confirmed by using NMR (H 1NMR) and gel
      permeation chromatography (GPC). Furthermore, liquid and solid film fluorescence
      excitation and emission spectra of the compounds were measured, and three
      polymers J1, J2 and J3 showed good fluorescence properties. The polymeric
      materials showed good film capacity, low cost and good thermal stability, and are
      expected to be widely applied in electroluminescent devices.

PMID- 30292186
TI  - Study on Molecular Recognition of Cucurbit[6]uril with Oxytetracycline Molecules
      by Spectroscopic Methods.
AB  - The molecular recognition of Cucurbit[6]uril (CB[6]) with Oxytetracycline (OTC)
      was studied by fluorescence spectra and UV spectra. The results showed that the
      fluorescence intensity and the UV absorbance of OTC were enhanced as host
      molecules were added, which showed that CB[6] and OTC were interacted. The
      inclusion of OTC was detected by fluorescence spectra and UV spectra with an
      apparent 1?1 interaction, which was also observed through the Benesi-Hildebrand
      method, OTC can form 1?1 complex with CB[6] under acid condition and it can not
      form complex with CB[6] under basic condition. The thermodynamic parameters
      (stability constants Ks, Gibbs free energy change DeltaG, enthalpy change, and
      entropy change) for the complexation process were determined. The thermodynamic
      studies indicated that the inclusion reactions between CB[6] and OTC were the
      hydrophobic interaction and endothermic process.

PMID- 30292187
TI  - Determination of Pb, Cr, Cd, and As in Aluminum-Plastic Packaging Materials via
      Inductively Coupled Plasma-Mass Spectrometry with Microwave Digestion.
AB  - Microwave digestion was performed to study the pretreatment methods of aluminum
      plastic packaging materials (APPMs). Five different digestion reagent
      combinations and proportions were thoroughly considered. Digestion results
      indicated that the most suitable reagent combination was sulfuric and nitric
      acids with the optimal proportion of 1?7 after the orthogonal experiment.
      Moreover, the possible reasons of the experimental phenomenon were analyzed. The
      contents of Pb, Cr, Cd, and As in APPMs were subsequently determined via
      inductively coupled plasma-mass spectrometry (ICP-MS). The satisfactory linearity
      of calibration curves was obtained with the linear correlation coefficients above
      0.999 5, and the instrument detection limits of Pb, Cr, Cd, and As for the
      current method were 0.215, 0.067, 0.006 and 0.020 ng.mL-1, respectively.
      Furthermore, the recoveries of standard addition ranged from 83.8% to 111.6%, and
      the relative standard deviations ranged from 0.5% to 7.4%. Two independent
      parallel determination results of Pb, Cr, Cd, and As in APPMs were approaching,
      and the student's t-test (confidence level, alpha=0.05) showed that the
      determination results had no significant differences. In conclusion, the present
      method exhibited fine linearity, low detection limit, high recovery, and good
      precision, which can accurately be utilized to analyze Pb, Cr, Cd, and As
      elements in APPMs or other similar materials.

PMID- 30292188
TI  - Improving the Accuracy of Camera-Based Heart Rate Measurement.
AB  - The heart rate (HR) measurements based on the camera (visible light) can be used
      to detect HR in non-contact mode, which has great application prospects both in
      the clinical application and home health care. However, CMOS sensors equipped
      with "rolling shutters", which distinguishes different lines per frame to become
      light sensitive at different moments in time, and stylized dithering of image
      acquisition (IMAQ) time caused by different computer programs running in the
      background will greatly influence the accuracy of the measured HR. In this paper,
      we analyze the phase error caused by CMOS sensor and the system error introduced
      by system sampling clock jitters. According to derivation, we propose two
      methods, amplitude-frequency superposition and a cubic spline interpolation
      reconstruction method based on actual schedules, that can be widely utilized in
      computer vision to overcome the camera phase error and sampling time fluctuation
      error. Amplitude of signal is analyzed and processed in amplitude-frequency
      domain in the method of amplitude-frequency superposition, which ignores the
      signal phase. Thus it can eliminate the phase error effectively. The cubic spline
      interpolation reconstruction method based on actual schedules can reconstructed
      the non-uniform sampling of images as uniform ones, so it can eliminate the
      system error involved by the system clock jitters. What's more, the properties of
      the methods are tested by applying them to both simulation experiments and real
      HR measurements. In the simulation, amplitude of measured signal is improved
      4.58% relative to the amplitude measured without the method of amplitude
      frequency superposition; root mean square error of signal's frequency, detected
      by the cubic spline interpolation reconstruction method based on actual
      schedules, is reduced more than 30%. In the real HR measurements, the amplitude
      of HR is raised to 33.5% relatively based on amplitude-frequency superposition.
      And the accuracy of HR is raised to approximately 40% by the method of cubic
      spline interpolation reconstruction method based on actual schedules. Therefore,
      the simulation experiments and real HR measurement proof that we can effectively
      eliminate the camera phase error based on the amplitude-frequency superposition
      extraction method, and the cubic spline interpolation based on the timetable
      method can effectively reduce the random error in IMAQ due to system clock
      jitters. These methods can both be widely used in dynamic signal detection based
      on machine vision.

PMID- 30292189
TI  - The Laser Rangefinder System in Quadrature Modem and Ambiguity Resolution.
AB  - We propose a laser rangefinder system based on the quadrature modem to achieve
      amplitude modulation, the method improves the accuracy of the phase measuring and
      simplifies the hardware design compared to the system with the secondary mixing
      methods, and to solve the range ambiguity caused by the measuring process, the
      ranging ambiguity resolving algorithm based on the over-determined equation is
      proposed, which avoids the searching of the optimal solution, finally the two K60
      laser rangefinders and three proposed rangefinders were experimented on the
      national standard baseline with the precision of 0.18 mm. the measuring time of
      the proposed system is less than 1.8 s, the average measuring error of those
      three prototypes is less than 2 mm, and the standard deviation is less than 1 mm
      within the measuring range 0~60 m. The experimental results show that the
      proposed design system of the rangefinder has higher measurement accuracy and
      speed in comparison with the traditional ones, which indicates the high
      reliability of the proposed design system.

PMID- 30292190
TI  - Supersonic jet spectroscopy of parent hemiporphycene: Structural assignment and
      vibrational analysis for S0 and S1 electronic states.
AB  - Hemiporphycene (HPc), a constitutional isomer of porphyrin, is studied under
      supersonic expansion conditions by means of laser-induced fluorescence, visible
      visible hole-burning experiments, single vibronic level fluorescence techniques,
      and quantum chemical calculations. Only one trans form of jet-cooled HPc is
      observed, in contrast to solution studies that evidence a mixture of two trans
      tautomeric forms separated in energy by ~1 kcal/mol. Reliable structural
      assignment is provided by simulating absorption and emission patterns at the
      density functional theory and time-dependent density functional theory levels of
      theory. The vibronic spectra are nicely reproduced for both electronic ground and
      lowest excited singlet states for the most stable trans form. In contrast to
      another porphyrin isomer, porphycene (Pc), no tunneling or photo-induced hydrogen
      transfer is detected. The lower symmetry of HPc compared with Pc and the
      concomitant non-equivalent positions of the inner-cavity nitrogen atoms result in
      a non-symmetric double minimum potential for tautomerization, larger energy
      barrier, and a longer tunneling distance, with the average intramolecular
      hydrogen bond length larger in HPc than in Pc. HPc readily forms hydrates that
      show red-shifted absorption relative to the bare molecule.

PMID- 30292191
TI  - Dissociation of GaN2+ and AlN2+ in APT: Electronic structure and stability in
      strong DC field.
AB  - We investigate from a theoretical point of view the stability of AlN2+ and GaN2+
      dications produced under high static electric fields like those reached in Atom
      Probe Tomography (APT) experiments. By means of quantum chemical calculations of
      the electronic structure of these molecules, we show that their stability is
      governed by two independent processes. On the one hand, the spin-orbit coupling
      allows some molecular excited states to dissociate by inter-system crossing. On
      the other hand, the action of the electric field lowers the potential energy
      barrier, which ensures the dication stability in standard conditions. We present
      a detailed example of field emission dynamics in the specific case of the 11Delta
      states for a parabolic tip, which captures the essentials of the process by means
      of a simplified model. We show that the dissociation dynamics of AlN2+ and GaN2+
      is completely different despite the strong resemblance of their electronic
      structure.

PMID- 30292192
TI  - Electronic structure and intramolecular interactions in three methoxyphenol
      isomers.
AB  - Electronic structures and intramolecular interactions of three methoxyphenol
      positional isomers and their rotamers have been studied using core X-ray
      photoelectron spectroscopy and quantum mechanical calculations. The structural
      calculations are benchmarked against published calculations of enthalpy of
      formation and rotational constants, and published experimental data. The good
      agreement obtained confirms the accuracy of the results. A single rotamer of each
      isomer was then selected and the C 1s photoelectron spectra calculated and
      compared with experiment. Good agreement is obtained, and the calculations were
      extended to investigate the effects of conformation. For 3-methoxyphenol, the
      difference in the C 1s binding energy of the conformers is small, <0.15 eV. For 2
      methoxyphenol, whose ground state includes an OH?OCH3 hydrogen bond, the higher
      energy rotamers show the largest shifts for the methyl carbon atom, whereas the
      ring carbon bonded to OH hardly shifts The theoretical differences in core level
      energies of the two rotamers of 4-MP are still smaller, <0.05 eV. By comparing
      calculations neglecting or including final state relaxation upon ionization, the
      relaxation energy of the phenyl carbons in all isomers is found to be ~0.5 eV,
      while that of the methyl groups is ~1.3 eV.

PMID- 30292193
TI  - Communication: First-principles evaluation of alkali ion adsorption and ion
      exchange in pure silica LTA zeolite.
AB  - Using first-principles calculations, we studied the adsorption of alkali ions in
      pure silica Linde Type A (LTA) zeolite. The probability of adsorbing alkali ions
      from solution and the driving force for ion exchange between Na+ and other alkali
      ions at the different adsorption sites were analyzed. From the calculated ion
      exchange isotherms, we show that it is possible to exchange Na+ with K+ and Rb+
      in water, but that is not the case for systems in a vacuum. We also demonstrate
      that a solvation model should be used for the accurate representation of ion
      exchange in an LTA and that dispersion interactions should be introduced with
      care.

PMID- 30292194
TI  - Solvent-mediated interactions between nanostructures: From water to Lennard-Jones
      liquid.
AB  - Solvent-mediated interactions emerge from complex mechanisms that depend on the
      solute structure, its wetting properties, and the nature of the liquid. While
      numerous studies have focused on the first two influences, here, we compare the
      results from water and Lennard-Jones liquid in order to reveal to what extent
      solvent-mediated interactions are universal with respect to the nature of the
      liquid. Besides the influence of the liquid, the results were obtained with
      classical density functional theory and brute-force molecular dynamics
      simulations which allow us to contrast these two numerical techniques.

PMID- 30292195
TI  - Spin-polarized and thermospin-polarized transport properties of phthalocyanine
      dimer based molecular junction with different transition metal atoms.
AB  - Based on the first-principles density functional theory combined with the non
      equilibrium Green's function method, we have studied the spin-polarized and
      thermospin-polarized transport properties of phthalocyanine (Pc) dimer based
      molecular junction with different transition metal (TM = Mn, Fe, Co, Ni) atoms.
      Our results show that the spin-polarized and thermospin-polarized transport
      properties can be effectively tuned by changing the central TM atoms, and only
      the MnPc dimer system exhibits perfect spin/thermal-spin filtering and sizeable
      giant magnetoresistance (GMR)/thermal-GMR effects. Meantime, the MnPc dimer
      system reveals a low-bias negative differential resistance effect under the
      parallel magnetic configuration. These findings suggest that the MnPc dimer
      system has great potential in developing the high-performance multifunctional
      spintronic and spin caloritronic devices.

PMID- 30292196
TI  - Communication: Can excitation energies be obtained from orbital energies in a
      correlated orbital theory?
AB  - This work shows that vertical excitation energies (characterized as single
      electron processes) can be expressed in terms of one-particle solutions from a
      self-consistent field problem built by means of correlated operators. There are
      two alternative ways of enforcing this proposal for i -> a transitions in a
      system (M): (1) by using only eigenvalues obtained for the cationic species
      reached after the removal of an electron from orbital i (M +) or (2) by combining
      these quantities with the eigenvalue associated with orbital i from the neutral M
      system. We demonstrate that those eigenvalues derived from the equation-of-motion
      formalism in terms of the coupled cluster approach including single and double
      substitutions for ionization potentials and electron affinities show excellent
      performance in reproducing these electronic transition energies by either path,
      with mean absolute deviations (MADs) between 0.02 and 0.06 eV. Moreover, the Kohn
      Sham Density Functional Theory (KS-DFT) methods from the Quantum Theory Project
      (QTP) family provide nice results in terms of the second approach (MADs from 0.21
      to 0.47 eV). However, DFT is not as successful as long as one takes into account
      only the eigenvalues of M +, although the respective excitation energies from QTP
      functionals are still reasonable (MADs between 0.55 and 0.74 eV). Ultimately,
      these relations can be used as a new consistency condition to develop KS-DFT
      approximations to the correlated orbital theory.

PMID- 30292197
TI  - A new generation of effective core potentials from correlated calculations: 3d
      transition metal series.
AB  - Recently, we have introduced a new generation of effective core potentials (ECPs)
      designed for accurate correlated calculations but equally useful for a broad
      variety of approaches. The guiding principle has been the isospectrality of all
      electron and ECP Hamiltonians for a subset of valence many-body states using
      correlated, nearly-exact calculations. Here we present such ECPs for the 3d
      transition series Sc to Zn with Ne-core, i.e., with semi-core 3s and 3p electrons
      in the valence space. Besides genuine many-body accuracy, the operators are
      simple, being represented by a few gaussians per symmetry channel with resulting
      potentials that are bounded everywhere. The transferability is checked on
      selected molecular systems over a range of geometries. The ECPs show a high
      overall accuracy with valence spectral discrepancies typically ~0.01-0.02 eV or
      better. They also reproduce binding curves of hydride and oxide molecules
      typically within 0.02-0.03 eV deviations over the full non-dissociation range of
      interatomic distances.

PMID- 30292198
TI  - Conformational properties of an artificial GM1 glycan cluster based on a metal
      ligand complex.
AB  - An artificial glycan cluster, in which 24 monosialotetrahexosylganglioside (GM1)
      glycans are transplanted to the interface of a metal-ligand complex, was recently
      proposed to investigate the interaction between GM1 glycan clusters and
      amyloidogenic proteins by NMR analysis. In this study, all-atom molecular
      dynamics simulations were performed to characterize the conformational properties
      of the artificial GM1 glycan cluster. We found that more than 65% of GM1 glycans
      are clustered by interchain hydrogen bonds. Interchain hydrogen bonds are mainly
      formed between Neu5Ac and Gal'. Pentamers were most frequently observed in the
      metal-ligand complex. GM1 glycans are tilted and hydrophobically interact with
      ligand moieties. The hydrophobic surface of the metal-ligand complex increases
      intrachain hydrogen bonds in each conformation of the GM1 glycans. The increase
      of intrachain hydrogen bonds stabilizes the local minimum conformations of the
      GM1 glycan in comparison with the monomeric one. Interchain hydrogen bonding
      between glycans and glycan-ligand hydrophobic interactions also contribute to
      this conformational stabilization. Our results provide the physicochemical
      properties of the new artificial GM1 glycan cluster under the thermal
      fluctuations for understanding its protein recognition and designing the drug
      material for amyloidogenic proteins.

PMID- 30292199
TI  - Machine learning enhanced global optimization by clustering local environments to
      enable bundled atomic energies.
AB  - We show how to speed up global optimization of molecular structures using machine
      learning methods. To represent the molecular structures, we introduce the auto
      bag feature vector that combines (i) a local feature vector for each atom, (ii)
      an unsupervised clustering of such feature vectors for many atoms across several
      structures, and (iii) a count for a given structure of how many times each
      cluster is represented. During subsequent global optimization searches,
      accumulated structure-energy relations of relaxed structural candidates are used
      to assign local energies to each atom using supervised learning. Specifically,
      the local energies follow from assigning energies to each cluster of local
      feature vectors and demanding the sum of local energies to amount to the
      structural energies in the least squares sense. The usefulness of the method is
      demonstrated in basin hopping searches for 19-atom structures described by single
      or double-well Lennard-Jones type potentials and for 24-atom carbon structures
      described by density functional theory. In all cases, utilizing the local energy
      information derived on-the-fly enhances the rate at which the global minimum
      energy structure is found.

PMID- 30292200
TI  - Davydov-type excitonic effects on the absorption spectra of parallel-stacked and
      herringbone aggregates of pentacene: Time-dependent density-functional theory and
      time-dependent density-functional tight binding.
AB  - Exciton formation leads to J-bands in solid pentacene. Describing these exciton
      bands represents a challenge for both time-dependent (TD) density-functional
      theory (DFT) and for its semi-empirical analog, namely, for TD density-functional
      tight binding (DFTB) for three reasons: (i) solid pentacene and pentacene
      aggregates are bound only by van der Waals forces which are notoriously difficult
      to describe with DFT and DFTB, (ii) the proper description of the long-range
      coupling between molecules, needed to describe Davydov splitting, is not easy to
      include in TD-DFT with traditional functionals and in TD-DFTB, and (iii) mixing
      may occur between local and charge transfer excitons, which may, in turn, require
      special functionals. We assess how far TD-DFTB has progressed toward a correct
      description of this type of exciton by including both a dispersion correction for
      the ground state and a range-separated hybrid functional for the excited state
      and comparing the results against corresponding TD-CAM-B3LYP/CAM-B3LYP+D3
      results. Analytic results for parallel-stacked ethylene are derived which go
      beyond Kasha's exciton model [M. Kasha, H. R. Rawls, and A. El-Bayoumi, Pure
      Appl. Chem. 11, 371 (1965)] in that we are able to make a clear distinction
      between charge transfer and energy transfer excitons. This is further confirmed
      when it is shown that range-separated hybrids have a markedly greater effect on
      charge-transfer excitons than on energy-transfer excitons in the case of parallel
      stacked pentacenes. TD-DFT calculations with the CAM-B3LYP functional and TD-lc
      DFT calculations lead to negligible excitonic corrections for the herringbone
      crystal structure, possibly because of an overcorrection of charge-transfer
      effects (CAM refers to Coulomb attenuated method). In this case, TD-DFT
      calculations with the B3LYP functional or TD-DFTB calculations parameterized to
      B3LYP give the best results for excitonic corrections for the herringbone crystal
      structure as judged from comparison with experimental spectra and with Bethe
      Salpeter equation calculations from the literature.

PMID- 30292201
TI  - On the phase diagram of Mackay icosahedra.
AB  - Using Monte Carlo and molecular dynamics simulations, we investigate the
      equilibrium phase behavior of a monodisperse system of Mackay icosahedra. We
      define the icosahedra as polyatomic molecules composed of a set of Lennard-Jones
      subparticles arranged on the surface of the Mackay icosahedron. The phase diagram
      contains a fluid phase, a crystalline phase, and a rotator phase. We find that
      the attractive icosahedral molecules behave similar to hard geometric icosahedra
      for which the densest lattice packing and the rotator crystal phase have been
      identified before. We show that both phases form under attractive interactions as
      well. When heating the system from the dense crystal packing, there is first a
      transition to the rotator crystal and then another to a fluid phase.

PMID- 30292202
TI  - Numerical investigation of effects of curvature and wettability of particles on
      heterogeneous condensation.
AB  - The incipient process of water vapor condensation around an insoluble nanoscale
      particle is studied by a molecular dynamics method, and the emphasis is placed on
      the effects of particle surface curvature and wettability. With a high initial
      saturation, two different linear nucleation stages are observed. At the first
      stage, clusters are formed by the water molecules adsorbed on the surface such
      that the nucleation rate is significantly affected by both water molecule flux
      toward the surface and adsorption probability. The former decreases with the
      surface curvature, and the latter is in proportion to the wettability. At the
      second stage, the nucleation rate is enhanced by the contribution of homogeneous
      clusters adsorbed to the surface and reduced by cluster merging because of the
      space limitation on small particles. As a result, the nucleation rate is
      basically not affected by the particle size. The average size of clusters keeps
      constant for a while, then starts to grow with a gradually increased growth rate.
      It is concluded that both curvature and wettability of the particle surface
      promote the cluster growing.

PMID- 30292203
TI  - Multiphoton photoelectron circular dichroism of limonene with independent
      polarization state control of the bound-bound and bound-continuum transitions.
AB  - Photoionization of randomly oriented chiral molecules with circularly polarized
      light leads to a strong forward/backward asymmetry in the photoelectron angular
      distribution. This chiroptical effect, referred to as Photoelectron Circular
      Dichroism (PECD), was shown to take place in all ionization regimes, from single
      photon to tunnel ionization. In the Resonance Enhanced Multiphoton Ionisation
      (REMPI) regime, where most of the table-top PECD experiments have been performed,
      understanding the role of the intermediate resonances is currently the subject of
      experimental and theoretical investigations. In an attempt to decouple the role
      of bound-bound and bound-continuum transitions in REMPI-PECD, we photoionized the
      (+)-limonene enantiomer using two-color laser fields in [1 + 1'] and [2 + 2']
      ionization schemes, where the polarization state of each color can be controlled
      independently. We demonstrate that the main effect of the bound-bound transition
      is to break the sample isotropy by orientation-dependent photoexcitation, in
      agreement with recent theoretical predictions. We show that the angular
      distribution of PECD strongly depends on the anisotropy of photoexcitation to the
      intermediate state, which is different for circularly and linearly polarized
      laser pulses. On the contrary, the helicity of the pulse that drives the bound
      bound transition is shown to have a negligible effect on the PECD.

PMID- 30292204
TI  - Dissociation of GaN2+ and AlN2+ in APT: Analysis of experimental measurements.
AB  - The use of a tip-shaped sample for the atom probe tomography technique offers the
      unique opportunity to analyze the dynamics of molecular ions in strong DC fields.
      We investigate here the stability of AlN2+ and GaN2+ dications emitted from an
      Al0.25Ga0.75N sample in a joint theoretical and experimental study. Despite the
      strong chemical resemblance of these two molecules, we observe only stable AlN2+,
      while GaN2+ can only be observed as a transient species. We simulate the emission
      dynamics of these ions on field-perturbed potential energy surfaces obtained from
      quantum chemical calculations. We show that the dissociation is governed by two
      independent processes. For all bound states, a mechanical dissociation is induced
      by the distortion of the potential energy surface in the close vicinity of the
      emitting tip. In the specific case of GaN2+, the relatively small electric dipole
      of the dication in its ground 13Sigma- and excited 11Delta states induces a weak
      coupling with the electric field so that the mechanical dissociation into Ga+ +
      N+ lasts for sufficient time to be observed. By contrast, the AlN2+ mechanical
      dissociation leads to Al2+ + N which cannot be observed as a correlated event.
      For some deeply bound singlet excited states, the spin-orbit coupling with lower
      energy triplet states gives another chance of dissociation by system inter-system
      crossing with specific patterns observed experimentally in a correlated time of
      flight map.

PMID- 30292205
TI  - Double-core-hole states in CH3CN: Pre-edge structures and chemical-shift
      contributions.
AB  - Spectra reflecting the formation of single-site double-core-hole pre-edge states
      involving the N 1s and C 1s core levels of acetonitrile have been recorded by
      means of high-resolution single-channel photoelectron spectroscopy using hard X
      ray excitation. The data are interpreted with the aid of ab initio quantum
      chemical calculations, which take into account the direct or conjugate nature of
      this type of electronic states. Furthermore, the photoelectron spectra of N 1s
      and C 1s singly core-ionized states have been measured. From these spectra, the
      chemical shift between the two C 1s-1 states is estimated. Finally, by utilizing
      C 1s single and double core-ionization potentials, initial and final state
      effects for the two inequivalent carbon atoms have been investigated.

PMID- 30292206
TI  - Accurate quantum molecular dynamics for multidimensional systems by the basis
      expansion leaping multi-configuration Gaussian (BEL MCG) method.
AB  - Quantum phenomena are quite often of critical importance in chemical reactions.
      Thus the development of quantum molecular dynamics approaches is required to
      study the role of quantum effects such as tunnelling in chemical processes. The
      basis expansion leaping multi-configuration Gaussian (BEL MCG) method has been
      developed to obtain time-propagated wave packets describing reactive molecular
      systems. Here we examine the applicability of BEL MCG to double well problems in
      several dimensions. We pay particular attention to what is required to yield
      highly accurate dynamics with respect to several key features of the BEL MCG
      propagation. The importance of using basis functions of a width appropriate to
      the nature of the potential energy surface in the region of configuration space
      where each basis function is located is highlighted, which has implications for
      virtually all quantum molecular dynamics methods utilising Gaussian basis
      functions.

PMID- 30292207
TI  - Polytetrahedral structure and glass-forming ability of simulated Ni-Zr alloys.
AB  - Binary Cu-Zr system is a representative bulk glassformer demonstrating high glass
      forming ability (GFA). From the first glance, the Ni-Zr system is the most
      natural object to expect the same behavior because nickel and copper are
      neighbors in the periodic table and have similar physicochemical properties.
      However, it is known that the Ni-Zr system has worse GFA than the Cu-Zr one. To
      understand the underlying physics, we investigate the Ni alpha Zr1-alpha system
      in whole concentration range alpha ? [0, 1]. Doing molecular dynamic simulations
      with a reliable embedded atom model potential, we show that the simulated Ni-Zr
      system also has relatively low GFA, which is comparable to that for an additive
      binary Lennard-Jones mixture without any chemical interaction. Icosahedral local
      ordering in Ni-Zr alloys is known to be less pronounced than that in the Cu-Zr
      ones; we see that as well. However, the icosahedron is not the only structural
      motif responsible for GFA. We find that the local structure of glassy Ni alpha
      Zr1-alpha alloys at 0.3 < alpha < 0.65 can be described in terms of Z11-Z16
      Kasper polyhedra with high density of topological defects including icosahedra as
      a part of this family. Concentration of topologically perfect Kasper polyhedra
      appears to be several times smaller than that in Cu-Zr. This is the reason for
      relatively poor GFA of the Ni-Zr system.

PMID- 30292208
TI  - Fully anharmonic infrared cascade spectra of polycyclic aromatic hydrocarbons.
AB  - The infrared (IR) emission of polycyclic aromatic hydrocarbons (PAHs) permeates
      our universe; astronomers have detected the IR signatures of PAHs around many
      interstellar objects. The IR emission of interstellar PAHs differs from their
      emission as seen under conditions on Earth as they emit through a collisionless
      cascade down through their excited vibrational states from high internal
      energies. The difficulty in reproducing interstellar conditions in the laboratory
      results in a reliance on theoretical techniques. However, the size and complexity
      of PAHs require careful consideration when producing the theoretical spectra. In
      this work, we outline the theoretical methods necessary to lead to fully
      theoretical IR cascade spectra of PAHs including: an anharmonic second order
      vibrational perturbation theory treatment, the inclusion of Fermi resonances
      through polyads, and the calculation of anharmonic temperature band shifts and
      broadenings (including resonances) through a Wang-Landau approach. We also
      suggest a simplified scheme to calculate vibrational emission spectra that retain
      the essential characteristics of the full IR cascade treatment and can directly
      transform low temperature absorption spectra in IR cascade spectra. Additionally
      we show that past astronomical models were in error in assuming a 15 cm-1
      correction was needed to account for anharmonic emission effects.

PMID- 30292209
TI  - Communication: Optically induced decoupling of the smectic-A and nematic order
      parameters at the AN phase transition in phototropic liquid crystals.
AB  - In the present work, by means of the photopyroelectric calorimetric
      investigations in liquid crystal/naphtopyran (NP) molecule mixtures, the effect
      of the photoisomerization of NP by UV light on the critical behavior of specific
      heat could be studied over the smectic-nematic phase transition. It is shown that
      the UV light irradiation of the sample can shift the critical exponent from a non
      universal value typical of the non-irradiated mixture to one close to that of the
      3D-XY universality class, predicted for such a transition. This witnesses the
      optically triggered reduction of the coupling between the smectic and nematic
      order parameters responsible for the deviation from the XY-like behavior. A
      tentative explanation is provided based on the weakening of the order parameter
      coupling caused by the NP molecules entering the smectic layers following the UV
      light illumination.

PMID- 30292210
TI  - Erratum: "Non-orthogonal configuration interaction with single substitutions for
      the calculation of core-excited states" [J. Chem. Phys. 149, 044116 (2018)].

PMID- 30292211
TI  - Exponential parameterization of wave functions for quantum dynamics: Time
      dependent Hartree in second quantization.
AB  - We derive equations for describing the time evolution of variational wave
      functions in linear and exponential parameterization with a second-quantization
      (SQ) formulation. The SQ formalism covers time-dependent Hartree (TDH), while
      exact states and approximate vibrational configuration interaction wave functions
      are described using state-transfer operators. We present detailed expressions for
      efficient evaluation of TDH in linear (L-TDH) and exponential (X-TDH)
      parametrization and an efficient implementation supporting linear scaling with
      respect to the number of degrees of freedom M when the Hamiltonian operator
      contains a constant number of terms per mode independently of the size of the
      system. The computational cost of the X-TDH method is reduced significantly
      compared to the L-TDH method for systems with many operator terms per mode such
      as is typical for accurate molecular potential-energy surfaces. Numerical results
      for L-TDH and X-TDH are presented which confirm the theoretical reduction of the
      M scaling compared to standard first-quantization formulations. Calculations on
      Henon-Heiles potentials with more than 105 dimensions and polycyclic aromatic
      hydrocarbons with up to 264 modes have been performed. Thus, the SQ formulation
      and the X-TDH method pave the way for studying the time-resolved quantum dynamics
      of large molecules.

PMID- 30292212
TI  - Accurate electron affinity of Ti and fine structures of its anions.
AB  - The high-resolution photoelectron energy spectra of atomic titanium and its
      hydride anions were obtained on a slow-electron velocity-map imaging spectrometer
      equipped with a cold ion trap. The cold ion trap employed in the present
      measurement was found to be very helpful for reducing the interference from the
      titanium hydride anions. The electron affinity of Ti was determined to be
      609.29(34) cm-1 or 75.54(4) meV. The accuracy was improved by a factor of 350
      compared with the previous result. The fine structures of Ti- were clearly
      resolved: 70.0(12)(4F5/2), 165.2(15)(4F7/2), and 285.2(15) cm-1 (4F9/2) above its
      ground state 4F3/2. Moreover, the measured electron affinity and vibrational
      frequency of TiH can be reproduced well using the high level calculations.

PMID- 30292213
TI  - Encoding and selecting coarse-grain mapping operators with hierarchical graphs.
AB  - Coarse-grained (CG) molecular dynamics (MD) can simulate systems inaccessible to
      fine-grained (FG) MD simulations. A CG simulation decreases the degrees of
      freedom by mapping atoms from an FG representation into agglomerate CG particles.
      The FG to CG mapping is not unique. Research into systematic selection of these
      mappings is challenging due to their combinatorial growth with respect to the
      number of atoms in a molecule. Here we present a method of reducing the total
      count of mappings by imposing molecular topology and symmetry constraints. The
      count reduction is illustrated by considering all mappings for nearly 50 000
      molecules. The resulting number of mapping operators is still large, so we
      introduce a novel hierarchical graphical approach which encodes multiple CG
      mapping operators. The encoding method is demonstrated for methanol and a 14-mer
      peptide. With the test cases, we show how the encoding can be used for automated
      selection of reasonable CG mapping operators.

PMID- 30292214
TI  - Charged nanorods at heterogeneously charged surfaces.
AB  - We study the spatial and orientational distribution of charged nanorods (rodlike
      counterions) as well as the effective interaction mediated by them between two
      plane-parallel surfaces that carry fixed (quenched) heterogeneous charge
      distributions. The nanorods are assumed to have an internal charge distribution,
      specified by a multivalent monopolar moment and a finite quadrupolar moment, and
      the quenched surface charge is assumed to be randomly distributed with equal mean
      and variance on the two surfaces. While equally charged surfaces are known to
      repel within the traditional mean-field theories, the presence of multivalent
      counterions has been shown to cause attractive interactions between uniformly
      charged surfaces due to the prevalence of strong electrostatic couplings that
      grow rapidly with the counterion valency. We show that the combined effects due
      to electrostatic correlations (caused by the coupling between the mean surface
      field and the multivalent, monopolar, charge valency of counterions) as well as
      the disorder-induced interactions (caused by the coupling between the surface
      disorder field and the quadrupolar moment of counterions) lead to much stronger
      attractive interactions between two randomly charged surfaces. The interaction
      profile turns out to be a nonmonotonic function of the intersurface separation,
      displaying an attractive minimum at relatively small separations, where the
      ensuing attraction can exceed the maximum strong-coupling attraction (produced by
      multivalent monopolar counterions between uniformly charged surfaces) by more
      than an order of magnitude.

PMID- 30292215
TI  - Semiclassical transition state theory based on fourth order vibrational
      perturbation theory: Model system studies beyond symmetric Eckart barrier.
AB  - The following one-dimensional model potential barriers are studied to compute the
      tunneling probabilities using semiclassical transition state theory (SCTST) based
      on fourth order vibrational perturbation theory (VPT4): (i) Morse barrier, (ii)
      asymmetric Eckart barrier, (iii) adjacent well barrier, and (iv) first order
      approximation to the symmetric Eckart barrier. The current investigation extends
      a previous study performed for the symmetric Eckart barrier. The performance of
      VPT4-SCTST is investigated for a broad range of energies, including the very deep
      tunneling regime (approximately 1% of the barrier height), and the results are
      compared to the exact quantum mechanical treatment, as well as to the popular
      second order vibrational perturbation theory (VPT2)-SCTST approach. While the
      VPT4-SCTST results are in excellent agreement with their quantum mechanical
      counterparts for a wide range of energies above and below the barrier, it is
      found for systems (ii) and (iv) that higher order terms (in n+12 ) in energy
      expansion are important for similarly excellent agreement in the deep tunneling
      regime. For the asymmetric Eckart barrier, the convergence properties of SCTST
      are analyzed in terms of its analytically known Siegert eigenvalues. A simple
      empirical modification of VPT2-SCTST advocated in the aforementioned previous
      work for the symmetric Eckart barrier is also tested here for the new model
      systems, and it is shown not to provide a uniformly systematic improvement.

PMID- 30292216
TI  - Effects of electron-phonon coupling on quantum interference in polyenes.
AB  - It has been well accepted that when quantum interference (QI) occurs in a single
      molecular junction comprised of a pi-conjugated molecule, the elastic pi-electron
      transmission is blocked, while the elastic sigma-electron transmission remains
      unchanged. When it comes to inelastic transport, in which passing electrons
      across the molecule trapped in between two metallic electrodes lose their energy
      through electron-phonon coupling, it is not necessarily obvious whether vibration
      affects the QI feature or not. In this paper, on the basis of a Huckel/tight
      binding model, we address the inelastic transport through linear and cyclic
      polyenes which are conditioned to show QI. The zeroth-order Green's function
      approximated by the negative inverse of the adjacency matrix of a molecular graph
      is used in conjunction with the lowest order expansion of the self-consistent
      Born approximation. Owing to the simplification of the model, it just finds the
      limited applicability for the pi-to-pi scattering. Only topological aspects of
      dephasing are included. In such a theoretical construct, the alternant nature of
      the pi-conjugated molecule is found helpful for classifying the dephasing
      patterns based on the parity of atomic sites. A rule is proposed, and it says
      that when both starred or both unstarred atoms are connected with the electrodes,
      QI always occurs, and atoms which belong to a different partite set from that of
      the atoms connected with the electrodes contribute to the inelastic pi-to-pi
      scattering. If QI occurs when a starred atom and an unstarred atom are connected
      with the electrodes, the contribution of the inelastic pi-to-pi scattering to the
      transport is expected to be unimportant.

PMID- 30292217
TI  - Ionic transport in nematic liquid crystals and alignment layer effects on
      electrode polarization.
AB  - The physical properties of a liquid crystal-ionic liquid system were
      investigated. Low-frequency dielectric spectroscopy for 4-cyano-4'-pentylbiphenyl
      (5CB) doped with 1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF 4) for the
      nematic and isotropic phase of host substances was performed. We obtained
      electrical conductivity values in the range from 298.2 K to 313.2 K and the
      conductivity anisotropy was confirmed. Further study of the relaxation process
      for bmim + allowed us to extract the relaxation frequencies and amplitudes from
      experimental data and confirm the temperature scaling; the thickness of the
      interfacial layers was estimated for the homogeneous and homeotropic alignments
      of the prepared composite. An attempt to unfold the ion contribution on the
      charge transport was made in order to better understand the electrode
      polarization process. In this work, the influence of the alignment layer and
      phase state on the interfacial layer formation in liquid crystal media will be
      explained better.

PMID- 30292218
TI  - Onset of natural selection in populations of autocatalytic heteropolymers.
AB  - Reduction of information entropy along with ever-increasing complexity is among
      the key signatures of life. Understanding the onset of such behavior in the early
      prebiotic world is essential for solving the problem of the origin of life. Here
      we study a general problem of heteropolymers capable of template-assisted
      ligation based on Watson-Crick-like hybridization. The system is driven off
      equilibrium by cyclic changes in the environment. We model the dynamics of 2
      mers, i.e., sequential pairs of specific monomers within the heteropolymer
      population. While the possible number of them is Z 2 (where Z is the number of
      monomer types), we observe that most of the 2-mers get extinct, leaving no more
      than 2Z survivors. This leads to a dramatic reduction of the information entropy
      in the sequence space. Our numerical results are supported by a general
      mathematical analysis of the competition of growing polymers for constituent
      monomers. This natural-selection-like process ultimately results in a limited
      subset of polymer sequences. Importantly, the set of surviving sequences depends
      on initial concentrations of monomers and remains exponentially large (2 L down
      from Z L for length L) in each of realizations. Thus, an inhomogeneity in initial
      conditions allows for a massively parallel search of the sequence space for
      biologically functional polymers, such as ribozymes. We also propose potential
      experimental implementations of our model in the contexts of either biopolymers
      or artificial nano-structures.

PMID- 30292219
TI  - Total electron scattering cross sections from thiophene for the (1-300 eV) impact
      energy range.
AB  - Experimental electron scattering cross sections for thiophene in the impact
      energy range from 1 to 300 eV have been measured with a magnetically confined
      electron transmission-beam apparatus. Random uncertainty limits have been
      estimated to be less than 5%, and systematic errors derived from acceptance angle
      limitations have also been identified and evaluated. Experimental values are
      compared with our previous low energy (1-15 eV) R-matrix and intermediate/high
      energy (15-300 eV) IAM-SCAR+I calculations finding reasonable agreement, within
      the combined uncertainty limits. Some of the low energy shape and core-excited
      resonances predicted by previous calculations are experimentally confirmed in
      this study.

PMID- 30292220
TI  - Collective modes of two-dimensional classical Coulomb fluids.
AB  - Molecular dynamics simulations have been performed to investigate in detail
      collective modes spectra of two-dimensional Coulomb fluids in a wide range of
      coupling. The obtained dispersion relations are compared with theoretical
      approaches based on quasi-crystalline approximation, also known as the quasi
      localized charge approximation, in the plasma-related context. An overall
      satisfactory agreement between theory and simulations is documented for the
      longitudinal mode at moderate coupling and in the long-wavelength domain at
      strong coupling. For the transverse mode, satisfactory agreement in the long
      wavelength domain is only reached at very strong coupling, when the cutoff wave
      number below which shear waves cannot propagate becomes small. The dependence of
      the cutoff wave-number for shear waves on the coupling parameter is obtained.

PMID- 30292221
TI  - Nascent O2 (a 1Deltag, v = 0, 1) rotational distributions from the
      photodissociation of jet-cooled O3 in the Hartley band.
AB  - We report rotational distributions for the O2 (a 1Deltag) fragment from the
      photodissociation of jet-cooled O3 at 248, 266, and 282 nm. The rotational
      distributions show a population alternation that favors the even states, as
      previously reported for a 300 K sample by Valentini et al. [J. Chem. Phys. 86,
      6745 (1987)]. The alternation from the jet-cooled precursor is much stronger than
      that observed by Valentini et al. and in contrast to their observations does not
      depend strongly on the O2 (a 1Deltag) vibrational state or photolysis wavelength.
      The odd/even alternation diminishes substantially when the ozone beam temperature
      is increased from 60 to 200 K, confirming its dependence on parent internal
      energy. The magnitude of the even/odd alternation in product rotational states
      from the cold ozone sample, its temperature dependence, and other experimental
      and theoretical evidence reported since 1987 suggest that the alternation
      originates from a Lambda-doublet propensity and not from a mass independent curve
      crossing effect, as previously proposed.

PMID- 30292222
TI  - Favoritism of quantum dot inter-Coulombic decay over direct and multi-photon
      ionization by laser strength and focus.
AB  - We study the dynamics of a two-electron system undergoing resonant excitation and
      inter-Coulombic decay (ICD) in a pair of quantum dots. The influence of the focus
      of the exciting laser on the ICD process is investigated for a pi-pulse with a
      close look on competing processes, i.e., direct ionization and multi-photon
      excitations. We scan through the field strength up to six Rabi cycles to show
      that ICD is still verifiable after several population inversions. With novel
      analyses, we determine for the first time populations of the different continuum
      states and thus conclude on the importance of several multi-photon excitation
      channels. Finally, we look into the influence of complex absorbing potentials on
      the dynamics.

PMID- 30292223
TI  - Accurate and efficient numerical simulation of dielectrically anisotropic
      particles.
AB  - A variety of electrostatic phenomena, including the structure of electric double
      layers and the aggregation of charged colloids and proteins, are affected by
      nonuniform electric permittivity. These effects are frequently ignored in
      analytical and computational studies and particularly difficult to handle in
      situations where multiple dielectric contrasts are present, such as in colloids
      that are heterogeneous in permittivity. We present an extension to the Iterative
      Dielectric Solver developed by Barros and Luijten [Phys. Rev. Lett. 113, 017801
      (2014)] that makes it possible to accurately compute the polarization of
      anisotropic particles with multiple dielectric contrasts. This efficient boundary
      element-method-based approach is applicable to geometries that are not amenable
      to other solvers, opening the possibility of studying collective phenomena of
      dielectrically anisotropic particles. We provide insight into the underlying
      physical reasons for this efficiency.

PMID- 30292225
TI  - The rotational spectrum and potential energy surface of the Ar-SiO complex.
AB  - The rotational spectra of five isotopic species of the Ar-SiO complex have been
      observed at high-spectral resolution between 8 and 18 GHz using chirped Fourier
      transform microwave spectroscopy and a discharge nozzle source; follow-up cavity
      measurements have extended these measurements to as high as 35 GHz. The spectrum
      of the normal species is dominated by an intense progression of a-type rotational
      transitions arising from increasing quanta in the Si-O stretch, in which lines up
      to v = 12 (~14 500 cm-1) were identified. A structural determination by isotopic
      substitution and a hyperfine analysis of the Ar-Si17O spectrum both suggest that
      the complex is a highly fluxional prolate symmetric rotor with a vibrationally
      averaged structure between T-shaped and collinear in which the oxygen atom lies
      closer to argon than the silicon atom, much like Ar-CO. To complement the
      experimental studies, a full dimensional potential and a series of effective
      vibrationally averaged, two-dimensional potential energy surfaces of Ar + SiO
      have been computed at the CCSD(T)-F12b/CBS level of theory. The equilibrium
      structure of Ar-SiO is predicted to be T-shaped with a well depth of 152 cm-1,
      but the linear geometry is also a minimum, and the potential energy surface has a
      long, flat channel between 140 and 180 degrees . Because the barrier between the
      two wells is calculated to be small (of order 5 cm-1) and well below the zero
      point energy, the vibrationally averaged wavefunction is delocalized over nearly
      100 degrees  of angular freedom. For this reason, Ar-SiO should exhibit large
      amplitude zero-point motion, in which the vibrationally excited states can be
      viewed as resonances with long lifetimes. Calculations of the rovibrational level
      pattern agree to within 2% with the transition frequencies of normal and isotopic
      ground state Ar-SiO, and the putative K a = +/-1 levels for Ar-28SiO, suggesting
      that the present theoretical treatment well reproduces the salient properties of
      the intramolecular potential.

PMID- 30292224
TI  - Blind prediction of protein B-factor and flexibility.
AB  - The Debye-Waller factor, a measure of X-ray attenuation, can be experimentally
      observed in protein X-ray crystallography. Previous theoretical models have made
      strong inroads in the analysis of beta (B)-factors by linearly fitting protein B
      factors from experimental data. However, the blind prediction of B-factors for
      unknown proteins is an unsolved problem. This work integrates machine learning
      and advanced graph theory, namely, multiscale weighted colored graphs (MWCGs), to
      blindly predict B-factors of unknown proteins. MWCGs are local features that
      measure the intrinsic flexibility due to a protein structure. Global features
      that connect the B-factors of different proteins, e.g., the resolution of X-ray
      crystallography, are introduced to enable the cross-protein B-factor predictions.
      Several machine learning approaches, including ensemble methods and deep
      learning, are considered in the present work. The proposed method is validated
      with hundreds of thousands of experimental B-factors. Extensive numerical results
      indicate that the blind B-factor predictions obtained from the present method are
      more accurate than the least squares fittings using traditional methods.

PMID- 30292226
TI  - Non-statistical intermolecular energy transfer from vibrationally excited benzene
      in a mixed nitrogen-benzene bath.
AB  - A chemical dynamics simulation was performed to model experiments [N. A. West et
      al., J. Chem. Phys. 145, 014308 (2016)] in which benzene molecules are
      vibrationally excited to 148.1 kcal/mol within a N2-benzene bath. A significant
      fraction of the benzene molecules are excited, resulting in heating of the bath,
      which is accurately represented by the simulation. The interesting finding from
      the simulations is the non-statistical collisional energy transfer from the
      vibrationally excited benzene C6H6 * molecules to the bath. The simulations find
      that at ~10-7 s and 1 atm pressure there are four different final temperatures
      for C6H6 * and the bath. N2 vibration is not excited and remains at the original
      bath temperature of 300 K. Rotation and translation degrees of freedom of both N2
      and C6H6 in the bath are excited to a final temperature of ~340 K. Energy
      transfer from the excited C6H6 * molecules is more efficient to vibration of the
      C6H6 bath than its rotation and translation degrees of freedom, and the final
      vibrational temperature of the C6H6 bath is ~453 K, if the average energy of each
      C6H6 vibration mode is assumed to be RT. There is no vibrational equilibration
      between C6H6 * and the C6H6 bath molecules. When the simulations are terminated,
      the vibrational temperatures of the C6H6 * and C6H6 bath molecules are ~537 K and
      ~453 K, respectively. An important question is the time scale for complete energy
      equilibration of the C6H6 * and N2 and C6H6 bath system. At 1 atm and 300 K, the
      experimental V-T (vibration-translation) relaxation time for N2 is ~10-4 s. The
      simulation time was too short for equilibrium to be attained, and the time for
      complete equilibration of C6H6 * vibration with translation, rotation, and
      vibration of the bath was not determined.

PMID- 30292227
TI  - Accurate double excitations from ensemble density functional calculations.
AB  - The recent use of a new ensemble in density functional theory (DFT) to produce
      direct corrections to the Kohn-Sham transitions yields the elusive double
      excitations that are missed by time-dependent DFT (TDDFT) with the standard
      adiabatic approximation. But accuracies are lower than for single excitations,
      and formal arguments about TDDFT suggest that a correction kernel is needed. In
      principle, ensemble DFT with direct corrections at the exchange level must yield
      accurate doubles in the weakly correlated limit. We illustrate with exact
      calculations and analytic results on the Hubbard dimer. We also explain the error
      in formal arguments in TDDFT.

PMID- 30292228
TI  - pi - pi stacking vs. C-H/ pi interaction: Excimer formation and charge resonance
      stabilization in van der Waals clusters of 9,9'-dimethylfluorene.
AB  - Studies of exciton and hole stabilization in multichromophoric systems underpin
      our understanding of electron transfer and transport in materials and
      biomolecules. The simplest model systems are dimeric, and recently we compared
      the gas-phase spectroscopy and dynamics of van der Waals dimers of fluorene, 9
      methylfluorene (MF), and 9,9'-dimethylfluorene (F1) to assess how sterically
      controlled facial encumbrance modulates the dynamics of excimer formation and
      charge resonance stabilization (CRS). Dimers of fluorene and MF show only excimer
      emission upon electronic excitation, and significant CRS as evidenced in a
      reduced ionization potential for the dimer relative the monomer. By contrast, the
      dimer of F1 shows no excimeric emission, rather structured emission from the
      locally excited state of a tilted (non pi-stacked) dimer, evidencing the
      importance of C-H/pi interactions and increased steric constraints that restrict
      a cofacial approach. In this work, we report our full results on van der Waals
      clusters of F1, using a combination of theory and experiments that include laser
      induced fluorescence, mass-selected two-color resonant two-photon ionization
      spectroscopy, and two-color appearance potential measurements. We use the latter
      to derive the binding energies of the F1 dimer in ground, excited, and cation
      radical states. Our results are compared with van der Waals and covalently linked
      clusters of fluorene to assess both the relative strength of pi-stacking and C
      H/pi interactions in polyaromatic assemblies and the role of pi-stacking in
      excimer formation and CRS.

PMID- 30292229
TI  - Adsorption and phase behavior of water-like fluid models with square-well
      attraction and site-site association in slit-like pores: Density functional
      approach.
AB  - The adsorption and phase behavior of two model fluids, both with square well
      inter-particle attraction and site-site associative interaction, in slit-like
      pores have been studied in the framework of a density functional theory. The mean
      field approach and the first-order mean spherical approximation have been applied
      to account for the attractive interactions. The chemical association effects are
      taken into account by using the first-order thermodynamic perturbation theory of
      Wertheim. A set of parameters for each fluid model has been chosen according to
      the work of [Clark et al., Mol. Phys. 104, 3561 (2006)], to describe successfully
      the vapor-liquid coexistence of water in the bulk phase. The influence of the
      slit-like pore width and of the strength of gas-solid interaction energy on the
      vapor-liquid coexistence envelope under confinement has been explored in detail.
      The theory and the results of the present work are valuable for further
      exploration of a wide set of models of associating fluids and of fluids with
      complex molecular architecture in different adsorbents, and to deal with
      activated carbon surfaces.

PMID- 30292230
TI  - Conformational change of a biomolecule studied by the weighted ensemble method:
      Use of the diffusion map method to extract reaction coordinates.
AB  - We simulate the nonequilibrium ensemble dynamics of a biomolecule using the
      weighted ensemble method, which was introduced in molecular dynamics simulations
      by Huber and Kim and further developed by Zuckerman and co-workers. As the order
      parameters to characterize its conformational change, we here use the coordinates
      derived from the diffusion map (DM) method, one of the manifold learning
      techniques. As a concrete example, we study the kinetic properties of a small
      peptide, chignolin in explicit water, and calculate the conformational change
      between the folded and misfolded states in a nonequilibrium way. We find that the
      transition time scales thus obtained are comparable to those using previously
      employed hydrogen-bond distances as the order parameters. Since the DM method
      only uses the 3D Cartesian coordinates of a peptide, this shows that the DM
      method can extract the important distance information of the peptide without
      relying on chemical intuition. The time scales are compared well with the
      previous results using different techniques, non-Markovian analysis and core-set
      milestoning for a single long trajectory. We also find that the most significant
      DM coordinate turns out to extract a dihedral angle of glycine, and the
      previously studied relaxation modes are well correlated with the most significant
      DM coordinates.

PMID- 30292231
TI  - A novel cerclage wiring technique in intertrochanteric femoral fractures treated
      by intramedullary nails in young adults.
AB  - BACKGROUND: Intertrochanteric femoral fractures (IFFs) in young adults, generally
      due to severe trauma, are increasingly presented. Different from IFFs in the
      geriatric population, these fractures in young adults are always comminuted and
      substantially displaced. Natural traction induced by musculature following IFFs
      determines closed reduction on a fracture table is extremely difficult. METHODS:
      To achieve anatomical reduction before intramedullary nail (IMN) fixation, we
      made an extended or a mini petrotrochantetic incision to facilitate temporary
      reduction using a pointed clamp. Subsequently, a curved and cannulated wire
      passer was employed to pass through a multistrand cable to surround displaced
      fragments and strengthen intertrochanteric fixation. Afterward, a standard
      procedure was conducted to nail the fracture. RESULTS: We used the surgical
      technique in 9 young patients with an age range of 28~ 48 years old. The
      fractures were categorized as AO/OTA 31-A2.2 (3 cases) and 31-A2.3 (6 cases). The
      injury-to-surgery interval was 2.5 days on average. Mean operation time was 55
      min. All fractures achieved anatomical reduction and healed within 14 weeks
      postoperatively without cable breakage, implant irritation or deep infection.
      CONCLUSIONS: In conclusion, the surrounding technique with cerclage wire in IFFs
      in young adults is an effective surgical technique with easily achieved
      anatomical reduction to facilitate operative maneuvers and fracture healing.

PMID- 30292232
TI  - Correction to: Culture of mesenchymal stem cells derived from equine synovial
      membrane in alginate hydrogel microcapsules.
AB  - The original article [1] contained a minor error regarding the mean diameter of
      the alginate microcapsules described in relation to Fig. 4 in the Results
      section. The microcapsules had an actual mean diameter of 3000 MUm instead of
      1000 MUm as mistakenly mentioned in the original article.

PMID- 30292234
TI  - Correction to: Treatment of periodontal intrabony defects using autologous
      periodontal ligament stem cells: a randomized clinical trial.
AB  - The original article [1] contains a major error carried across the captions of
      Tables 1, 2, and 3. In each table caption, the data were expressed as "mean +/-
      standard deviation (SD)"; unfortunately, the authors had mistakenly expressed the
      data as "mean +/- standard error (SE)" instead. As such, all mentions of "mean +/
      standard error" in those table captions should of course state "mean +/-
      standard deviation". The authors are deeply sorry for these errors.

PMID- 30292233
TI  - Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric
      cancer cell migration.
AB  - BACKGROUND: Exosomes are extracellular vesicles that mediate cellular
      communication in health and diseases. Neutrophils could be polarized to a pro
      tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil
      regulation remains unclear. METHODS: We investigated the effects of gastric
      cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils
      and elucidated the underlying mechanisms. RESULTS: GC-Ex prolonged neutrophil
      survival and induced expression of inflammatory factors in neutrophils. GC-Ex
      activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex
      transported high mobility group box-1 (HMGB1) that activated NF-kappaB pathway
      through interaction with TLR4, resulting in an increased autophagic response in
      neutrophils. Blocking HMGB1/TLR4 interaction, NF-kappaB pathway, and autophagy
      reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer
      cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation.
      Furthermore, HMGB1 expression was upregulated in gastric cancer tissues.
      Increased HMGB1 expression was associated with poor prognosis in patients with
      gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly
      as exosomes derived from gastric cancer cell lines in neutrophil activation.
      CONCLUSION: We demonstrate that gastric cancer cell-derived exosomes induce
      autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-kappaB
      signaling, which provides new insights into mechanisms for neutrophil regulation
      in cancer and sheds lights on the multifaceted role of exosomes in reshaping
      tumor microenvironment.

PMID- 30292236
TI  - Experiences of aging in place in the United States: protocol for a systematic
      review and meta-ethnography of qualitative studies.
AB  - BACKGROUND: By 2035, older adults will outnumber children for the first time in
      the United States (US). In light of its aging population, the US has supported
      services focused on enabling older adults to continue living in their current
      homes, a model commonly described as "aging in place." The lived experience of
      aging in place is not well documented in existing systematic reviews. The aims of
      this systematic review are to synthesize and evaluate the existing qualitative
      evidence on experiences of aging in place in the US and identify knowledge gaps
      and directions for future studies. METHODS: Six electronic bibliographic
      databases (PubMed, PsycINFO, CINAHL, Web of Science, EMBASE, and Sociological
      Abstracts) will be searched. Studies presenting qualitative data on the
      experiences of older adults currently aging in place in the US will be included.
      Covidence software will be used to screen studies and extract data. The Joanna
      Briggs Institute checklist for qualitative research will be used to assess
      quality and risk of bias of included studies. We will use meta-ethnography,
      following the method described by Noblit and Hare, to synthesize and evaluate the
      results of the included studies. DISCUSSION: To the best of our knowledge, this
      is the first systematic review to integrate and synthesize the findings of
      qualitative studies of aging in place focusing on older adults in the US. The
      findings of this review will provide in-depth knowledge on lived experiences of
      aging in place and address important gaps in existing work. SYSTEMATIC REVIEW
      REGISTRATION: International Prospective Register of Systematic Reviews
      (PROSPERO): CRD42018102847.

PMID- 30292235
TI  - CpG binding protein (CFP1) occupies open chromatin regions of active genes,
      including enhancers and non-CpG islands.
AB  - BACKGROUND: The mechanism by which protein complexes interact to regulate the
      deposition of post-translational modifications of histones remains poorly
      understood. This is particularly important at regulatory regions, such as CpG
      islands (CGIs), which are known to recruit Trithorax (TrxG) and Polycomb group
      proteins. The CxxC zinc finger protein 1 (CFP1, also known as CGBP) is a subunit
      of the TrxG SET1 protein complex, a major catalyst of trimethylation of H3K4
      (H3K4me3). RESULTS: Here, we used ChIP followed by high-throughput sequencing
      (ChIP-seq) to analyse genomic occupancy of CFP1 in two human haematopoietic cell
      types. We demonstrate that CFP1 occupies CGIs associated with active
      transcription start sites (TSSs), and is mutually exclusive with H3K27
      trimethylation (H3K27me3), a marker of polycomb repressive complex 2. Strikingly,
      rather than being restricted to active CGI TSSs, CFP1 also occupies a substantial
      fraction of active non-CGI TSSs and enhancers of transcribed genes. However,
      relative to other TrxG subunits, CFP1 was specialised to TSSs. Finally, we found
      enrichment of CpG-containing DNA motifs in CFP1 peaks at CGI promoters.
      CONCLUSIONS: We found that CFP1 is not solely recruited to CpG islands as it was
      originally defined, but also other regions including non-CpG island promoters and
      enhancers.

PMID- 30292237
TI  - Nanomedicine for drug delivery in South Africa: a protocol for systematic review.
AB  - BACKGROUND: The emergence of nanomedicine in the past decade has changed the
      landscape of disease diagnosis and treatment. Nanomedicine makes use of
      nanostructures for applications in different fields of medicine, including drug
      delivery, biosensors, neuro-electronic interfaces, in vivo imaging, and cell
      specific molecular interactions. Despite its relative infancy, nanomedicine has
      generated a significant body of research as evidenced by peer reviewed literature
      and several patents. This proposed systematic review will focus specifically on
      drug delivery systems in which nanoparticles are used to enhance the
      pharmacological and therapeutic properties of drugs. The strength of
      nanoparticulate drug delivery systems is their ability to alter the
      pharmacokinetics and bio-distribution of drugs. Globally, the discourse on
      nanomedicine is dominated by research being done in the developed countries of
      Europe and in the United States of America. Less attention has been given to the
      applications of nanomedicine in developing countries, particularly Africa. There
      is dearth of information on the applications of nanomedicine in terms of drug
      delivery with particular reference to which diseases are being targeted generally
      in Africa. The review will describe the specific diseases that are being targeted
      and the progress being made in South Africa, with a view to determining whether
      the applications of nanomedicine are being appropriated to address the context
      specific challenges in this country or if they mimic what is being done globally.
      METHODS: Keywords related to nanomedicine and drug delivery will be combined to
      build a search strategy for each of the following databases: PubMed, Cochrane
      Library (including Cochrane Central Register of Controlled Trials (CENTRAL),
      Cochrane Database of Systematic Reviews, Cochrane Methodology Register), Google
      Scholar, NHS Health Technology Assessment Database and Web of Science. We will
      also check reference lists of included studies for other eligible reports and
      search unpublished data. To ensure that the search is comprehensive, grey
      literature will be searched extensively. Literature to be included will have
      nanomedicine in drug delivery as the primary application and report on the
      specific diseases that are targeted in South Africa. Two authors will
      independently screen the search output, select studies and extract data;
      discrepancies will be resolved by consensus and discussion. When no consensus is
      reached, the third author will be consulted DISCUSSION: The systematic review
      will inform the government, policy-makers, investors, health professionals,
      scientists, and engineers about the applications of nanomedicine in drug
      delivery. In particular, it will identify the diseases targeted by the
      application of nanomedicine for drug delivery and the progress being made in
      South Africa as the disease burden of this country differs from that of developed
      countries where nanomedicine has been widely used for drug delivery. SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO CRD42017057388.

PMID- 30292238
TI  - Correction to: Enhanced differentiation of human pluripotent stem cells into
      pancreatic progenitors co-expressing PDX1 and NKX6.1.
AB  - The original article [1] contains a number of small errors which the authors
      would like to clarify.

PMID- 30292239
TI  - Population-based studies of relationships between dietary acidity load, insulin
      resistance and incident diabetes in Danes.
AB  - BACKGROUND: It has been suggested that the acidity of the diet may be related to
      increased risk of type 2 diabetes. To investigate this hypothesis, we tested if
      the acidity of the diet, measured as the Potential Renal Acid Load (PRAL) score,
      was associated with incident diabetes and diabetes-related intermediary traits.
      METHODS: A total of 54,651 individuals from the Danish Diet, Cancer and Health
      (DCH) cohort were included in the prospective cox regression analyses of incident
      diabetes over a 15 years follow-up period. Moreover, 5724 Danish individuals with
      baseline data from the Inter99 cohort were included in the cross sectional,
      multivariate and logistic regression analyses of measures of insulin sensitivity,
      insulin release and glucose tolerance status derived from an oral glucose
      tolerance test (OGTT). RESULTS: In the DCH cohort a trend analysis showed that
      quintiles of PRAL score were, after multifactorial adjustment, associated with a
      higher incidence of diabetes (ptrend = 6 * 10- 7). HR for incident diabetes was
      1.24 (1.14; 1.35) (p = 7 * 10- 7) between first and fifth PRAL score quintile. In
      Inter99 higher PRAL score associated with insulin resistance as estimated by
      lower BIGTT-Si (an OGTT-derived index of insulin sensitivity) (p = 4 * 10- 7) and
      Matsuda index of insulin sensitivity (p = 2 * 10- 5) as well as higher HOMA-IR (p
      = 0.001). No association was observed for measures of insulin release, but higher
      PRAL score was associated with lower OGTT-based disposition index. CONCLUSIONS: A
      high dietary acidity load is associated with a higher risk of diabetes among
      middle-aged Danes. Although adjustment for BMI attenuated the effect sizes the
      association remained significant. The increased risk of diabetes may be related
      to our finding that a high dietary acidity load associates with impaired insulin
      sensitivity.

PMID- 30292240
TI  - Friend retrovirus infection induces the development of memory-like natural killer
      cells.
AB  - Traditionally, NK cells belong to the innate immune system and eliminate virus
      infected cells through their germline-encoded receptors. However, NK cells were
      recently reported to possess memory-like functions that were predominantly
      provided by hepatic NK cells. Memory properties were mainly documented in contact
      hypersensitivity models or during cytomegalovirus infections. However, the
      precise role and the physiologic importance of memory-like NK cells during
      retroviral infections are still under investigation. Here, we show that Friend
      retrovirus (FV) infection of mice induced a population of phenotypically memory
      like NK cells at 28 days post infection. Upon secondary antigen encounter, these
      NK cells showed an increased production of the pro-inflammatory cytokines
      IFNgamma and TNFalpha as well as the death ligand FasL in comparison to naive NK
      cells. Furthermore, we found an augmented elimination of antigen-matched but not
      antigen-mismatched target cells by these memory-like NK cells. In adoptive cell
      transfer experiments, equal antiviral activities of splenic and hepatic memory
      like NK cells during the late phase of acute FV infection were found. Our results
      strongly imply the existence and antiviral activity of spleen and liver memory
      like NK cells in FV infection, which efficiently respond upon secondary exposure
      to retroviral antigens.

PMID- 30292241
TI  - Correction to: The role of fibrinolysis inhibition in engineered vascular
      networks derived from endothelial cells and adipose-derived stem cells.
AB  - The original article [1] contains numerous value errors in the graphs in Fig. 2b
      regarding the markers describing the values for total tubule length and mean
      tubule length without aprotinin at 2.5 mg/ml concentration of fibrinogen. The
      corrected version of this figure can be viewed ahead.

PMID- 30292242
TI  - Shared decision making and antibiotic benefit-harm conversations: an
      observational study of consultations between general practitioners and patients
      with acute respiratory infections.
AB  - BACKGROUND: Little research has examined whether shared decision making (SDM)
      occurs in consultations for acute respiratory infections (ARIs), including what,
      and how, antibiotic benefits and harms are discussed. We aimed to analyse the
      extent and nature of SDM in consultations between GPs and patients with ARIs, and
      explore communication with and without the use of patient decision aids. METHODS:
      This was an observational study in Australian general practices, nested within a
      cluster randomised trial of decision aids (for acute otitis media [AOM], sore
      throat, acute bronchitis) designed for general practitioners (GPs) to use with
      patients, compared with usual care (no decision aids). Audio-recordings of
      consultations of a convenience sample of consenting patients seeing a GP for an
      ARI were independently analysed by two raters using the OPTION-12 (observing
      patient involvement in decision making) scale (maximum score of 100) and 5 items
      (about communicating evidence) from the Assessing Communication about Evidence
      and Patient Preferences (ACEPP) tool (maximum score of 5). Patients also self
      completed a questionnaire post-consultation that contained items from CollaboRATE
      5 (perceptions of involvement in the decision-making process), a decisional
      conflict scale, and a decision self-efficacy scale. Descriptive statistics were
      calculated for each measure. RESULTS: Thirty-six consultations, involving 13 GPs,
      were recorded (20 for bronchitis, 10 sore throat, 6 AOM). The mean (SD) total
      OPTION-12 score was 29.4 (12.5; range 4-54), with item 12 (need to review
      decision) the highest (mean = 3) and item 10 (eliciting patients' preferred level
      of decision-making involvement) the lowest (mean = 0.1). The mean (SD) total
      ACEPP score was 2 (1.6), with the item about discussing benefits scoring highest.
      In consultations where a decision aid was used (15, 42%), compared to the 21
      usual care consultations, mean observer-assessed SDM scores (OPTION-12, ACEPP
      scores) were higher and antibiotic harms mentioned in all (compared to only 1)
      consultations. Patients generally reported high decision involvement and self
      efficacy, and low decisional conflict. CONCLUSIONS: The extent of observer
      assessed SDM between GPs and patients with ARIs was generally low. Balanced
      discussion of antibiotic benefits and harms occurred more often when decision
      aids were used.

PMID- 30292244
TI  - Sight and Perspective.

PMID- 30292243
TI  - Massive hemothorax due to two bleeding sources with minor injury mechanism: a
      case report.
AB  - BACKGROUND: Massive hemothorax resulting from a minor injury mechanism is
      considered to be rare particularly when the diaphragm is injured. We report a
      case of massive hemothorax with bleeding from the intercostal artery and
      diaphragmatic damage caused by minor blunt trauma. CASE PRESENTATION: An 83-year
      old Japanese man was transported to our hospital 3 hours after falling out of
      bed. Computed tomography revealed hemothorax and multiple rib fractures. He
      underwent fluid resuscitation and a tube thoracostomy, but he became
      hemodynamically unstable. Contrast-enhanced computed tomography revealed
      worsening hemothorax with contrast extravasation 4 hours after arrival at the
      hospital. Emergency angiography indicated hemorrhage in the area supplied by the
      tenth intercostal artery. Transcatheter arterial embolization stabilized his
      vital signs for a short period. However, further hemodynamic stabilization
      required a thoracotomy, which revealed diaphragmatic trauma, which was removed
      and sutured before fixing his fractured ribs. His postoperative course was
      uneventful, and he was transferred to another hospital for rehabilitation without
      complications on hospital day 29. CONCLUSIONS: Minor mechanisms of blunt trauma
      can cause rib fractures and massive hemothorax. Traumatic diaphragm injury should
      be considered a differential diagnosis if hemodynamic instability persists after
      transcatheter arterial embolization in patients with lower level rib fractures.

PMID- 30292245
TI  - A Strange Calculus.

PMID- 30292246
TI  - Widespread Dermatophytosis in a Patient Treated for Leprosy Type II Reactional
      State after MDT/WHO-MB Release.

PMID- 30292247
TI  - Focal Seizures with Corresponding Neuroimaging and Electroencephalographic
      Findings in a Patient with Scolex Remnants within a Calcified Cysticercus.

PMID- 30292248
TI  - Chikungunya and Zika Viruses: Global Emerging Health Threats.

PMID- 30292250
TI  - Defining Value for Echocardiography: Why and How?

PMID- 30292249
TI  - Reliability and validity of a Turkish version of the Sexual Quality of Life -
      Male questionnaire: a methodological study.
AB  - Background: The aim of this methodological study was to assess the reliability
      and validity of the Sexual Quality of Life - Male (SQoL-M) questionnaire
      translated and adapted to measure the sexual quality of life of men in Turkey and
      Northern Cyprus. Methods: To assess the reliability and validity of the Turkish
      version of the SQoL-M questionnaire, in January and February 2017 we formed a
      sample of 128 men from Ankara, Turkey, and Girne, Northern Cyprus, to complete
      the questionnaire. Two weeks later, 65 of these men completed the questionnaire
      during a retest. Factor analysis was conducted to evaluate the questionnaire's
      factor structure, internal consistency and test-retest reliability analyses were
      used to assess reliability and Pearson's correlation coefficient was used to
      measure criterion-related validity. Results: Cronbach's alpha for the Turkish
      version of the SQoL-M questionnaire was 0.91, with corrected item-total score
      correlations ranging from 0.432 to 0.819. The test-retest correlation, calculated
      to compare scale scores of both groups of participants, was 0.83 (P<0.001). We
      also observed a statistically significant relationship between the Turkish
      version of the SQoL-M questionnaire and the Arizona Sexual Experience scale.
      Conclusions: The Turkish version of the SQoL-M questionnaire is a valid, reliable
      instrument for evaluating the sexual quality of life of men in Turkey and
      Northern Cyprus.

PMID- 30292251
TI  - Two facets of sweat: A defensive factor in skin tissues and an accelerating
      factor for allergic skin diseases.

PMID- 30292252
TI  - Preoperative evaluation of pelvine lymph node metastasis in high risk prostate
      cancer with intravoxel incoherent motion (IVIM) MRI.
AB  - OBJECTIVES: To evaluate benign and malignant pelvine lymph nodes in prostate
      cancer patients with biexponential intravoxel incoherent motion (IVIM) MRI of the
      prostate prior to radical prostatectomy. METHODS: The ethics committee approved
      this retrospective study with waiver of informed consent. From February 2012 to
      November 2013 43 patients with histopathologically proven prostatic cancer were
      included. All patients were examined applying a standardized MRI protocol
      including IVIM diffusion weighted imaging with multiple b-values ranging from 0
      to 950 s/mm2. MR imaging was performed one day prior to radical prostatectomy.
      Thereafter, extended lymph node resection was performed. For each MRI all visible
      lymph nodes were registered and calculated as individual regions of interest.
      These findings were correlated with postoperative pathology. The apparent
      diffusion coefficient ADC, the diffusion coefficient D and the perfusion fraction
      f were calculated from IVIM DWI using a biexponential fit. RESULTS: A total of
      120 lymph nodes were detected on MRI. 95 of these were determined as benign and
      25 as malignant. The average ADC was significantly lower in malignant compared to
      benign lymph nodes (0.88 * 10-3 vs 1.67 * 10-3 mm2/s, p < 0.001). Likewise, the
      average diffusion coefficient D was significantly lower in lymph node metastasis
      (0.54 * 10-3 vs 1.10 * 10-3 mm2/s, p < .001). The signal rate due to perfusion
      was significantly higher in malignant compared to benign nodes (33.4% vs. 27.1%,
      p = 0.02). CONCLUSIONS: Applying biexponential IVIM MRI demonstrates significant
      differences in diffusion parameters ADC and D, as well as in the perfusion
      fraction f for benign and malignant lymph nodes. Therefore, IVIM might help to
      further improve the preoperative assessment of lymph nodes in MRI.

PMID- 30292253
TI  - The evolution of magnetic resonance enterography in the assessment of motility
      disorders in children.
AB  - Gastrointestinal symptoms including constipation, diarrhoea, pain and bloating
      represent some of the most common clinical problems for patients. These symptoms
      can often be managed with cheap, widely available medication or will
      spontaneously resolve. However, for many patients, chronic GI symptoms persist
      and frequently come to dominate their lives. At one end of the spectrum there is
      Inflammatory Bowel Disease (IBD) with a clearly defined but expensive treatment
      pathway. Contrasting with this is Irritable Bowel Syndrome (IBS), likely a
      collection of pathologies, has a poorly standardised pathway with unsatisfactory
      clinical outcomes. Managing GI symptoms in adult populations is a challenge. The
      clinical burden of gastrointestinal disease is also prevalent in paediatric
      populations and perhaps even harder to treat. In this review we explore some of
      the recent advances in magnetic resonance imaging (MRI) to study the
      gastrointestinal tract. Complex in both its anatomical structure and its
      physiology we are likely missing key physiological markers of disease through
      relying on symptomatic descriptors of gut function. Using MRI we might be able to
      characterise previously opaque processes, such as non-propulsive contractility,
      that could lead to changes in how we understand even common symptoms like
      constipation. This review explores recent advances in the field in adult
      populations and examines how this safe, objective and increasingly available
      modality might be applied to paediatric populations.

PMID- 30292254
TI  - Breast MRI for prediction of lymphovascular invasion in breast cancer patients
      with clinically negative axillary lymph nodes.
AB  - OBJECTIVE: To retrospectively assess magnetic resonance imaging (MRI) findings
      that can predict lymphovascular invasion (LVI) in invasive breast cancer patients
      who were diagnosed with clinically negative axillary lymph nodes (LNs)
      preoperatively. METHODS: This study included 140 lesions of 140 patients who
      underwent preoperative breast MRI and breast surgery, with omission of axillary
      LN dissection. Clinical characteristics and MRI findings were evaluated. The T2
      signal intensity (SI) ratio (mean T2 SI of the tumor/mean T2 SI of the muscle),
      tumor apparent diffusion coefficient (ADC) value, peritumoral ADC value,
      peritumor-tumor ADC ratio (peritumoral maximum ADC value/tumor mean ADC value),
      and ADC value of the contralateral breast parenchyma were retrospectively
      assessed. Statistical analyses were performed to identify significant factors for
      predicting LVI. Inter-observer variability was calculated. RESULTS: The tumor ADC
      value (all ages: p = 0.005; age <= 55: p < 0.001), peritumoral ADC value (age <=
      55: p = 0.04), and peritumor-tumor ADC ratio (all ages: p < 0.001; age <= 55: p <
      0.001) were significantly associated with LVI on univariate analysis.
      Multivariate logistic regression analysis revealed significant differences in the
      pathological size of the invasive component and the tumor ADC value for
      predicting LVI (odds ratio [OR]: 3.43; 95% confidence interval [CI]: 1.41-8.32; p
      = 0.007; OR: 16.0; 95% CI: 1.89-136; p = 0.01, respectively). Inter-observer
      agreement was substantial for the tumor ADC value (intraclass correlation
      coefficient [ICC] = 0.77; 95% CI: 0.70-0.83) and the ADC value of the
      contralateral breast parenchyma (ICC = 0.68; 95% CI: 0.59-0.76). There was
      moderate agreement for the peritumoral ADC value (ICC = 0.53; 95% CI: 0.40-0.64)
      and the peritumor-tumor ADC ratio (ICC = 0.49; 95% CI: 0.35-0.61) and fair
      agreement for the T2 SI ratio (ICC = 0.30; 95% CI: 0.15-0.45). CONCLUSION: We
      found that the tumor ADC value, peritumoral ADC value, and peritumor-tumor ADC
      ratio were predictive MRI findings for LVI in patients aged <=55. The tumor ADC
      value was the most significant predictor for LVI; moreover, inter-observer
      agreement for the tumor ADC value was substantial between two blinded observers
      with differences in interpretation experience.

PMID- 30292255
TI  - Radiological prediction of positive circumferential resection margin in
      oesophageal cancer.
AB  - PURPOSE: A positive circumferential resection margin (CRM) is regarded as a poor
      prognostic indicator in oesophageal cancer (OC) but its prediction can be
      challenging. MRI is used to predict a threatened CRM in rectal cancer but is not
      commonly performed in OC unlike PET/CT, which is now routinely used. Therefore,
      this study assessed the additional predictive value of PET-defined tumour
      variables compared with EUS and CT T-stage. The prognostic significance of CRM
      status was also assessed. MATERIALS AND METHODS: This retrospective study
      included 117 consecutive patients [median age 64.0 (range 24-78), 102 males, 110
      adenocarcinomas, 6 squamous cell carcinoma (SCC), 1 neuro-endocrine] treated
      between 1st March 2012 and 31st July 2015. A binary logistic regression model
      tested 5 staging variables; EUS T-stage (<=T2 vs >= T3), CT T-stage (<=T2 vs >=
      T3), PET metabolic tumour length (MTL), PET metabolic tumour width (MTW) and the
      maximum standardised uptake value (SUVmax). RESULTS: The CRM was positive in
      43.6%. Sixty-seven (57.3%) patients received neo-adjuvant chemotherapy (NACT), 31
      patients (26.5%) underwent surgery alone and 19 patients (16.2%) had neo-adjuvant
      chemo-radiotherapy (NACRT). Median overall survival (OS) was 36.0 months (95%
      confidence interval (CI) 24.1-47.9) and the 2-year OS was 55.4%. A binary
      logistic regression model showed EUS >= T3 tumours were independently and
      significantly more likely to have a positive CRM than EUS <= T2 tumours (HR
      5.188, 95% CI 1.265-21.273, p = 0.022). CT T-stage, PET MTL, PET MTW and SUVmax
      were not significantly associated with CRM status (p = 0.783, 0.852, 0.605 and
      0.413, respectively). There was a significant difference in OS between CRM
      positive and negative groups (X2 4.920, df 1, p = 0.027). CONCLUSION: Advanced
      EUS T-stage is associated with a positive CRM, but PET-defined tumour variables
      are unlikely to provide additional predictive information. This study
      demonstrates the continued benefit of EUS as part of a multi-modality OC staging
      pathway.

PMID- 30292256
TI  - Diagnostic efficacy of b value (2000 s/mm2) diffusion-weighted imaging for
      prostate cancer: Comparison of a reduced field of view sequence and a
      conventional technique.
AB  - OBJECTIVES: To compare high b value (2000 s/mm2) reduced field-of-view (rFOV)
      diffusion-weighted imaging (DWI) with a conventional DWI sequence in terms of
      image quality, as well as diagnostic performance concerning prostate cancer (PCa)
      detection and tumor staging at 3 T. METHODS: Sixty-one patients underwent rFOV
      DWI and conventional DWI due to clinical suspicious of PCa were retrospectively
      recruited. Imaging qualities were evaluated qualitatively and quantitatively by
      two blinded radiologists. Thirty-two subjects with detailed pathology reports
      were further analyzed for diagnostic efficacy using the Prostate Imaging
      Reporting and Data System (PI-RADS) version 2. The PCa detection rate,
      sensitivity, specificity, and PI-RADS staging changes were compared between the
      DWI sequences. RESULTS: Qualitative evaluation regarding image quality was
      significantly better in rFOV DWI than in the conventional DWI (all P < 0.05). ADC
      contrast with rFOV DWI was rated significantly higher than the conventional DWI
      in both peripheral zone (PZ) and transition zone (TZ) (P = 0.001 for PZ, and P = 
      0.003 for TZ). Regarding diagnostic efficacy, rFOV DWI yielded higher tumor
      detection, sensitivity and the area under the curve (AUC) than the conventional
      DWI (all P < 0.05), except the AUC in the PZ for one reader (P = 0.262).
      Conventional DWI achieved slightly higher specificity for the PZ and TZ but with
      no significant difference except for one reader in the PZ (P = 0.009).
      CONCLUSION: The rFOV DWI could offer improved image quality and yielded better
      diagnostic performance in terms of higher tumor detection rate and relatively
      precise staging for PCa compared to the conventional sequence.

PMID- 30292257
TI  - Recurrent renal cell carcinoma following nephrectomy and ablation therapy:
      Radiology perspective.
AB  - Renal cell carcinoma (RCC) is the most common renal malignancy, accounting for
      approximately 2% of adult malignancies and 4% of new cancer cases in the United
      States every year. Imaging guided ablative therapy, including radiofrequency (RF)
      ablation, cryotherapy and microwave has gained popularity over the last decade in
      treatment of small tumors. Antiangiogenic therapy has set itself to be the
      standard of care for many patients with metastasis these days. With hope for more
      research, survival rates of metastatic RCC may increase from a current 2-year
      survival rate of approximately 20%. Variation in imaging surveillance protocol in
      terms of frequency, modality, and duration is noted among guidelines developed by
      several organizations. In this review article, we will discuss follow-up imaging
      protocols, patterns of RCC recurrence following different modalities of
      treatment, imaging appearance, as well as usual and unusual sites of metastatic
      disease.

PMID- 30292258
TI  - A comparison of full-field digital mammograms versus 2D synthesized mammograms
      for detection of microcalcifications on screening.
AB  - OBJECTIVES: To compare the observer agreement of microcalcification detection on
      synthetic 2D images to full field digital mammography (FFDM) at screening and
      determine if calcifications can be detected to the same degree and given the same
      BI-RADS assessment. MATERIAL AND METHODS: Two-experienced radiologists
      retrospectively reviewed synthetic 2D images and FFDM, in separate sessions, to
      detect microcalcifications and provide a BIRADS assessment. A third experienced
      breast radiologist reviewed the cases that were disagreed upon and gave a final
      assessment. Between March 2016-December 2016, 414 women obtained a screening
      mammogram with tomosynthesis and acquisition of FFDM. 71 cases had combined FFDM
      and tomosynthesis images, calcifications visible on FFDM or no calcifications
      present, which comprised the study group. Synthetic 2D images were constructed
      from the DBT images. During session 1, all synthetic 2D images for the 71 cases
      were reviewed. During session 2, all the FFDM images for the 71 cases were
      reviewed. Tomosynthesis images were not reviewed. The agreement of detection of
      calcifications and BIRADS assessment between radiologists for FFDM and synthetic
      2D images were assessed using Cohen's kappa test. Fisher's exact test was used to
      detect the differences in calcification identification among various breast
      densities on FFDM and synthetic 2D images. RESULTS: For the detection of
      calcifications between synthetic 2D images and FFDM, there was moderate to
      substantial agreement (p-values < 0.0001) for the two radiologist. For the BIRADS
      assessments, the agreement between synthetic 2D imaging and FFDM was moderate (p
      values < 0.0001). The inter-reader agreement for detection of calcifications was
      fair for using synthetic 2D and moderate for using FFDM (p-value < 0.0001). The
      final inter-reader agreement between FFDM and synthetic 2D images for the
      detection of calcifications was moderate (p-values < 0.0001) with the addition of
      the third reader. For the final BI-RADS assessment, there was moderate agreement
      between synthetic 2D imaging and FFDM (p-value < 0.0001). The two readers did not
      demonstrate a significant difference in the detection of microcalcifications for
      those who were dense or non-dense (p-value range 0.076-0.302). CONCLUSION:
      Radiologist interpreting synthetic 2D imaging and FFDM have similar frequency for
      detection of calcifications and BIRADS assessment. A synthetic 2D mammogram may
      be a sufficient replacement for FFDM at screening.

PMID- 30292259
TI  - A prospective clinical study using a dynamic contrast-enhanced CT-protocol for
      detection of colorectal liver metastases.
AB  - OBJECTIVE: To evaluate a dynamic contrast-enhanced CT-protocol and compare this
      method with standard of care monophasic portovenous CT for detection of
      colorectal liver metastases. MATERIALS AND METHODS: A dynamic contrast-enhanced
      CT protocol was developed to detect liver metastasis in patients suffering from
      colorectal cancer, in clinical practice. The study was approved by the Hospital
      Ethics Committee. Written informed consent was obtained from all patients. 135
      patients were included in this prospective study. All patients were naive to
      treatment. A dynamic contrast-enhanced CT was performed, followed by routine
      monophasic portovenous CT of thorax-abdomen-pelvis. 42 of these patients
      presented with liver metastasis. The number and lesion conspicuity of detected
      liver metastasis on dynamic contrast-enhanced CT using perfusion maps, was
      compared to monophasic CT. RESULTS: 135 patients were included, of which 42
      presented with metastases to the liver. Dynamic contrast-enhanced CT outperformed
      portovenous CT for detection as well as conspicuity of colorectal liver
      metastasis, at a relatively low dose increment. Wilcoxon Signed Rank test had a p
      value of 0.016 and <0.001 respectively for detection and conspicuity of
      colorectal liver metastasis. CONCLUSION: Dynamic contrast-enhanced CT increases
      the detection of colorectal liver metastasis, especially for lesions smaller than
      15 mm, when compared to monophasic portovenous CT. Dynamic contrast-enhanced CT
      also has the added advantage of improved lesion conspicuity, which can positively
      influence reader confidence and clinical workflow.

PMID- 30292260
TI  - Textural differences between renal cell carcinoma subtypes: Machine learning
      based quantitative computed tomography texture analysis with independent external
      validation.
AB  - OBJECTIVE: To develop externally validated, reproducible, and generalizable
      models for distinguishing three major subtypes of renal cell carcinomas (RCCs)
      using machine learning-based quantitative computed tomography (CT) texture
      analysis (qCT-TA). MATERIALS AND METHODS: Sixty-eight RCCs were included in this
      retrospective study for model development and internal validation. Another 26
      RCCs were included from public databases (The Cancer Genome Atlas-TCGA) for
      independent external validation. Following image preparation steps
      (reconstruction, resampling, normalization, and discretization), 275 texture
      features were extracted from unenhanced and corticomedullary phase CT images.
      Feature selection was firstly done with reproducibility analysis by three
      radiologists, and; then, with a wrapper-based classifier-specific algorithm. A
      nested cross-validation was performed for feature selection and model
      optimization. Base classifiers were the artificial neural network (ANN) and
      support vector machine (SVM). Base classifiers were also combined with three
      additional algorithms to improve generalizability performance. Classifications
      were done with the following groups: (i), non-clear cell RCC (non-cc-RCC) versus
      clear cell RCC (cc-RCC) and (ii), cc-RCC versus papillary cell RCC (pc-RCC)
      versus chromophobe cell RCC (chc-RCC). Main performance metric for comparisons
      was the Matthews correlation coefficient (MCC). RESULTS: Number of the
      reproducible features is smaller for the unenhanced images (93 out of 275)
      compared to the corticomedullary phase images (232 out of 275). Overall
      performance metrics of the machine learning-based qCT-TA derived from
      corticomedullary phase images were better than those of unenhanced images. Using
      corticomedullary phase images, ANN with adaptive boosting algorithm performed
      best for discrimination of non-cc-RCCs from cc-RCCs (MCC = 0.728) with an
      external validation accuracy, sensitivity, and specificity of 84.6%, 69.2%, and
      100%, respectively. On the other hand, the performance of the machine learning
      based qCT-TA is rather poor for distinguishing three major subtypes. The SVM with
      bagging algorithm performed best for discrimination of pc-RCC from other RCC
      subtypes (MCC = 0.804) with an external validation accuracy, sensitivity, and
      specificity of 69.2%, 71.4%, and 100%, respectively. CONCLUSIONS: Machine
      learning-based qCT-TA can distinguish non-cc-RCCs from cc-RCCs with a satisfying
      performance. On the other hand, the performance of the method for distinguishing
      three major subtypes is rather poor. Corticomedullary phase CT images provide
      much more valuable texture parameters than unenhanced images.

PMID- 30292261
TI  - Staging/restaging performance of F18-fluorodeoxyglucose positron emission
      tomography/magnetic resonance imaging in breast cancer: A review and meta
      analysis.
AB  - PURPOSE: This systematic review and meta-analysis was performed to assess the
      staging/restaging performance of F18-fluorodeoxyglucose (FDG) positron emission
      tomography (PET)/magnetic resonance imaging (MRI) in breast cancer. METHODS: A
      comprehensive search was performed in PubMed databases for studies reporting the
      staging performance of F18-FDG PET/MRI in breast cancer from the inception of
      these databases to January 29, 2018. Eight studies were included in this
      systematic review and meta-analysis. Pooled estimates of patient- and lesion
      based sensitivity, specificity, positive likelihood ratio (PLR), negative
      likelihood ratio (NLR), and diagnostic odds ratio (DOR) of F18-FDG PET/MRI were
      calculated alongside 95% confidence intervals (CIs). A summary receiver operating
      characteristic curve (SROC) was plotted and the area under the SROC curve (AUC)
      was determined alongside the Q* index. RESULTS: The patient-based overall pooled
      sensitivity, specificity, PLR, NLR, DOR, and AUC of F18-FDG PET/MRI for staging
      in breast cancer were 0.98 (95% CI, 0.95-0.99), 0.87 (95% CI, 0.76-0.95), 4.59
      (95% CI, 1.91-11.05), 0.03 (95% CI, 0.01-0.09), 203.07 (95% CI, 50.33-819.38),
      and 0.99, respectively. The lesion-based overall pooled sensitivity, specificity,
      PLR, NLR, DOR, and AUC of F18-FDG PET/MRI for staging in breast cancer were 0.91
      (95% CI, 0.88-0.94), 0.95 (95% CI, 0.92-0.97), 11.28 (95% CI, 4.25-29.96), 0.07
      (95% CI, 0.02-0.22), 286.46 (95% CI, 64.15-1279.17), and 0.99, respectively. The
      overall diagnostic accuracies (Q* index) of the staging performance of F18-FDG
      PET/MRI in breast cancer were 0.96 (patient-based analysis) and 0.95 (lesion
      based analysis). CONCLUSION: F18-FDG PET/MRI has excellent diagnostic
      staging/restaging performance in patients with breast cancer, and thus should be
      considered for staging of patients with breast cancer.

PMID- 30292262
TI  - Sub-solid nodule detectability in seven observers of seventy-nine clinical cases:
      comparison between ultra-low-dose chest digital tomosynthesis with iterative
      reconstruction and chest radiography by receiver-operating characteristics
      analysis.
AB  - PURPOSE: To compare sub-solid nodules detectability (SSND) between ultra-low-dose
      chest digital tomosynthesis (ULD-CDT) with/without iterative reconstruction (IR)
      and chest radiography (CR) by using low-dose computed tomography (LDCT) as the
      standard of reference (SOR). MATERIALS AND METHODS: Institutional Review Board
      approved this study and written informed consent was obtained. In a single visit,
      79 subjects underwent ULD-CDT at 120 kV and 10 mA, CR and LDCT (effective dose:
      0.171, 0.117 and 3.52 mSv, respectively). Sixty-three coronal images were
      reconstructed using CDT with/without IR. SOR as to SSN presence was determined
      based on LDCT images. Seven radiologists recorded SSN presence and locations by
      continuously-distributed rating. Receiver-operating characteristic (ROC) analysis
      was used to compare SSND of ULD-CDT with/without IR and CR, in total and
      subgroups classified by nodular longest diameter (LD) (> or < 9 mm) and mean CT
      attenuation value (CTAV) (> or < -600 Hounsfield of Unit (HU)). Detection
      sensitivity (DS) was compared among 4 groups classified by combination of the
      identical thresholds: nodular LD (9 mm) and mean CTAV (-600 HU) in each of ULD
      CDT with/without IR and CR with Friedman and Wilcoxon signed rank test. RESULTS:
      SSND for total 105 SSNs as well as larger SSNs with nodular LD of 9 mm or more at
      ULD-CDT with IR was higher than either that at ULD-CDT without IR or CR, as the
      areas under the ROC curve were 0.66 +/- 0.02, 0.59 +/- 0.01 and 0.52 +/- 0.01,
      respectively (p < 0.05). DS at ULD-CDT with IR was 69.5 +/- 10.8% in groups with
      larger (LD > 9 mm) and more-attenuated (>-600 HU) SSNs, and higher than in the
      other 3 groups (p < 0.05). CONCLUSION: ULD-CDT with IR demonstrated better SSND
      than that without IR or CR, with increased DS for larger and more-attenuated SSNs
      compared with the remaining ones.

PMID- 30292264
TI  - Children centered care: Minimizing the need for anesthesia with a multi-faceted
      concept for MRI in children aged 4-6.
AB  - PURPOSE: To evaluate the need for general anesthesia (GA) in MRI in children aged
      4-6 years, using a multi-faceted concept, Children Centered Care (CCC), compared
      to a standard setup. MATERIALS AND METHODS: In this prospective study of 81
      children, we developed and tested a multi-faceted concept, CCC, for MRI in
      children aged 4-6 without GA, comparing it to a standard setup. The CCC included:
      1) an interactive app, 2) a trained pediatric team, 3) a children's lounge with a
      toy-scanner, and 4) a child-friendly multimedia environment in the MRI room.
      Patients were included from February-September 2016 and 2017. The use of GA was
      evaluated, image quality was assessed and a cost-benefit analysis was done.
      RESULTS: We included 40 children in the control group and 41 in the CCC group.
      Mean age was 5.8 years and 48 (59%) were males. Neuro and orthopedic imaging
      accounted for 58 (72%) and 22 (27%), respectively. With the CCC setup 39/41 (95%)
      completed a diagnostic MRI without GA compared to 17/40 (43%) in the control
      group (p < 0.001). Image quality was not different between the groups (p = 0.37).
      The setup proved cost-effective with a payback time of two years in a Danish
      setting with 250 eligible patients per year. CONCLUSION: With the multi-faceted
      concept CCC, the use of GA for MRI in children aged 4-6 was markedly reduced to
      5%, image quality was maintained and the setup was cost-effective.

PMID- 30292263
TI  - CT-response patterns and the role of CT-textural features in inoperable
      abdominal/retroperitoneal soft tissue sarcomas treated with trabectedin.
AB  - PURPOSE: To evaluate CT patterns and textural features of soft tissue sarcomas
      following trabectedin therapy as well as their suitability for predicting
      therapeutic response. MATERIAL AND METHODS: A total of 31 patients (18 female, 13
      male; mean age, 58.0years; range, 38-79years) with sarcoma under trabectedin as a
      third-line therapy between October 2008 and July 2017 underwent baseline and
      follow-up contrast-enhanced CT. Response evaluation was based on modifiedCHOI
      criteria and RECIST1.1, classified as partial response(PR), stable disease(SD),
      progressive disease(PD). For CT-texture analysis (CTTA), mean, entropy and
      uniformity of intensity/skewness/entropy of co-occurrence matrix (COM) and
      contrast of neighboring-grey-level-dependence-matrix (NGLDM) were calculated.
      RESULTS: Following CHOI-criteria, 9 patients achieved PR, 10 SD and 12 PD.
      RECIST1.1. classified patients into 5 PR, 15 SD and 11 PD. A frequent (n = 6/31;
      19.3%) pattern of response was tumor liquefaction. In responders differences in
      entropy of entropy-NGLDM(p = 0.028) and uniformity-NGLDM(p = 0.021), in non
      responders entropy of average(p = 0.039), deviation(p = 0.04) and uniformity of
      deviation(p = 0.013) occured between baseline and follow-up. Mean intensity and
      average were higher when liquefication occured(p = 0.03; p = 0.02), whereas mean
      deviation was lower(p = 0.02) at baseline compared to other response patterns.
      Differences in mean(p = 0.023), entropy(p = 0.049) and uniformity(p = 0.023) of
      entropy-NGLDM were found between responders and non-responders at follow-up. For
      the mean of heterogeneity a cut-off value was calculated for prediction of
      response in baseline CTTA (0.12; sensitivity 89%; specificity 77%). CONCLUSION: A
      frequent pattern of response to trabectedin was tumor liquefication being
      responsible for pseudoprogression, therefore modifiedCHOI should be preferred.
      Single CT-textural features can be used complementarily for prediction and
      monitoring response to trabectedin.

PMID- 30292265
TI  - Breast cancer staging: Combined digital breast tomosynthesis and automated breast
      ultrasound versus magnetic resonance imaging.
AB  - PURPOSE: To investigate whether combined Digital breast tomosynthesis and
      Automated breast volume scanner (DBT-ABVS) are comparable to Magnetic resonance
      imaging (MRI) in staging breast cancer. METHODS: We retrospectively included
      seventy-three patients with histologically proven breast cancer who underwent
      preoperative DBT, ABVS and 1.5 T MRI in the period July 2015-July 2016. Two
      radiologists in consensus recorded the number, site and Breast imaging-reporting
      and data system (BI-RADS) category of breast findings during two independent
      reading strategies, i.e. DBT-ABVS vs. MRI. Using histology or 1-year follow up as
      the standard of reference, we calculated the accuracy for cancer of both imaging
      strategies. Bland-Altman analysis was used to evaluate the agreement between MRI
      vs. DBT or ABVS in cancer size assessment. RESULTS: Patients showed a total of
      160 lesions (108 malignant and 52 benign). Malignant lesions were unifocal,
      multifocal, multicentric and biltateral in 53, 15, 4 and 1 cases, respectively.
      Diagnostic accuracy of DBT-ABVS vs. MRI was comparable for all cancers (90.0%
      [95%C.I. 84.3-94.2] vs. 93.8% [95%C.I. 88.8-97.0], respectively). DBT-ABVS showed
      lower sensitivity and positive predictive values for additional disease (76.5%
      [95%C.I. 58.8-89.3] vs. 91.7% [95%C.I. 84.6-96.1], and 78.8% [95%C.I. 61.0-91.0]
      vs 93.4% [95%C.I. 86.9-97.3], respectively). Compared to MRI, ABVS + DBT missed 6
      lesions, including two invasive cancers and one extensive intravascular invasion
      associated to ductal carcinoma in situ. Bland-Altman analysis showed ABVS to
      agree with MRI at a higher extent than DBT in assessing cancer size. CONCLUSIONS:
      Though less performing than MRI, DBT-ABVS showed acceptable diagnostic accuracy
      in staging breast cancer. This strategy might be used if MRI is unavailable or
      unfeasible.

PMID- 30292266
TI  - Clinical implication of radiographic scores in acute Middle East respiratory
      syndrome coronavirus pneumonia: Report from a single tertiary-referral center of
      South Korea.
AB  - The aim of this study is to determine the earliest cutoff of radiographic score
      as a potential prognostic indicator of fatal outcomes in patients with acute
      Middle East respiratory syndrome coronavirus (MERS-CoV) pneumonia. The
      institutional review board approved this retrospective study. Serial chest
      radiographies (CXRs) were obtained from viral exposure until death or discharge
      in 35 patients with laboratory confirmed MERS-CoV infection. Radiographic scores
      were calculated by multiplying a four-point scale of involved lung area and three
      point scale of abnormal opacification, in each of the six lung zones. Receiver
      operating characteristics (ROC) analyses were performed to identify optimal day
      and radiographic score for the prediction of respiratory distress, and univariate
      and multivariate logistic regression analyses were performed to assess
      significant predictive factors for intubation or tracheostomy. Among 35 patients
      (22 men, 13 women; median age: 48 years), 25 demonstrated abnormal opacity on CXR
      (MERS pneumonia), whereas no abnormality was detected in 10 patients (MERS upper
      respiratory tract infection). Seven patients required ventilator support
      (intubation group) and three of them eventually expired. The average incubation
      period was 5.4 days (standard deviation, +/-2.8; range, 2-11). Patients in the
      intubation group had a higher incidence of diffuse lung involvement, higher
      radiographic scores, and fibrosing sequela on follow up study compared with those
      in the non-intubation group. However, patients' age and comorbidity did not
      differ significantly between the two groups. The ROC analysis revealed an area
      under curve of 0.726 for the radiographic score on day 10 with an optimal cutoff
      score of 10 for prediction of intubation, with a sensitivity of 71% and
      specificity of 67%. Our study suggest that MERS patients with radiographic score
      > 10 on day 10 from viral exposure require aggressive therapy with careful
      surveillance and follow-up evaluation.

PMID- 30292267
TI  - Diagnostic value of diffusion-weighted imaging and 18F-FDG-PET/CT for the
      detection of unknown primary head and neck cancer in patients presenting with
      cervical metastasis.
AB  - BACKGROUND AND PURPOSE: Head and neck squamous cell carcinoma (HNSCC) may present
      with cervical metastases without an apparent primary tumor. Detecting the primary
      tumor results in more targeted treatment. Acquisition of DWI is improving with
      less artifacts and image distortion. We assessed the diagnostic value of DWI and
      18F-FDG-PET/CT for detecting primary tumors in patients presenting with nodal
      metastasis of an unknown primary HNSCC. MATERIALS AND METHODS: For this
      retrospective study we included 31 patients (male/female ratio = 23/8, median age
      = 66 years, age range = 40-80 years) who presented with a pathologically proven
      cervical nodal metastasis from HNSCC without overt primary tumor location between
      January 2013 and November 2016 and underwent both DWI and 18F-FDG-PET/CT. Both
      modalities were assessed qualitatively and quantitatively. With ROC analysis we
      determined the optimal cut-off for imaging parameters in separating occult
      malignancy from benign tissue. RESULTS: Qualitative analysis of MRI including DWI
      resulted in a sensitivity of 81.3% (95%CI) = 53.7-95.0) and specificity of 73.3%
      (95%CI = 44.8-91.1). With qualitative scoring of 18F-FDG-PET/CT a sensitivity and
      specificity of 93.8% (95%CI = 67.8-99.7) and 73.3% (95%CI = 44.8-91.1) were
      found. With quantitative analysis sensitivity and specificity of SUVmax were
      81.3% (95%CI = 53.6-95.0) and 93.3% (95%CI = 66.0-99.7), respectively. Combining
      DWI and 18F-FDG-PET/CT resulted in a sensitivity of 93.8% (95%CI = 67.7-99.7%)
      and specificity of 60.0% (95%CI = 32.9-82.5%). CONCLUSION: In this study on HNSCC
      patients presenting with clinically UP lesions the diagnostic accuracy of
      qualitative analysis with DWI and 18F-FDG-PET/CT and quantitative analysis of 18F
      FDG-PET/CT using SUVmax were high. Adding DWI did not improve the accuracy of 18F
      FDG-PET/CT.

PMID- 30292268
TI  - Native cardiac T1 Mapping: Standardized inline analysis of long and short axis at
      three identical 1.5 Tesla MRI scanners.
AB  - BACKGROUND: Interpretation of native T1 time values remains difficult due to
      limited hard- and software comparability and the lack of measurement
      recommendations for the number of slices and their orientation. To provide a
      standardized comparison of native T1 time values in short and long axis and to
      investigate the interscanner reproducibility. METHODS: 78 cardiac MRIs in 26
      healthy volunteers were performed with three structurally identical 1.5 T MRI
      scanners. A commercially available software package for T1 mapping with automatic
      in-line motion correction was used for analysis. On T1 mapping images regions of
      interest were manually placed in each of the 16 myocardial segments according to
      the AHA model in three short and three long axis. RESULTS: A total of 2652 ROIs
      were drawn and 102 segments per volunteer were analysed. Interscanner
      reproducibility was high and the mean myocardial T1 time value for all evaluated
      segments was 996 +/- 34 ms. Significant variations of T1 time values were found
      between heart segments in the same axis. Mean T1 time values were comparable
      between long and short axis but differed in 33% of corresponding short and long
      axis segments. CONCLUSIONS: Native T1 time values in short and long axis are
      highly reproducible but can vary significantly between heart segments in the same
      axis. Comparability between corresponding short and long axis segments is
      limited. To get representative results native T1 time values should be obtained
      in more than one heart segment and for follow-up studies identical segments
      should be used to avoid a systematic bias.

PMID- 30292269
TI  - Radiological images of interstitial pneumonia in mixed connective tissue disease
      compared with scleroderma and polymyositis/dermatomyositis.
AB  - OBJECTIVE: Little has been reported on the radiological and pathological findings
      of interstitial pneumonia in mixed connective tissue disease (MCTD). There may be
      possible difference in treatment response and prognosis between the imaging
      patterns of systemic sclerosis (SSc)-like and polymyositis/dermatomyositis
      (PM/DM)-like. The purpose of this study was to examine whether the radiological
      images of interstitial pneumonia in MCTD presented SSc-like or PM/DM-like
      pattern, and to assess whether the imaging patterns corresponded to clinical and
      pathological features. MATERIALS AND METHODS: This retrospective study included
      29 patients with interstitial pneumonia who underwent surgical lung biopsy; 10
      with SSc, 10 with PM/DM, and 9 with MCTD. High resolution computed tomography
      (HRCT) images were classified as SSc, PM/DM, or the other pattern by two
      radiologists independently without clinical information. The pathology of the
      lung specimens from MCTD patients were evaluated and compared with the imaging
      pattern. RESULTS: The concordance rate between clinical diagnosis and
      radiological pattern was 100% in SSc patients, and 80% in PM/DM patients. Among
      patients with MCTD, imaging patterns were classified as SSc pattern in 4 (MCTD
      SSc), PM/DM pattern in 4 (MCTD-PM/DM) and other in one. The imaging patterns did
      not always correlate with the clinical findings in MCTD patients. Pathologically,
      plasma cell infiltration and organizing pneumonia were relatively more frequent
      in MCTD-PM/DM, and smooth muscle hyperplasia was relatively more frequent in MCTD
      SSc. CONCLUSION: HRCT images in MCTD patients can be classified as SSc pattern or
      PM/DM pattern. MCTD-SSc and MCTD-PM/DM were corresponded to similar pathological
      findings of SSc and PM/DM.

PMID- 30292270
TI  - Quantitative CT detects changes in airway dimensions and air-trapping after
      bronchial thermoplasty for severe asthma.
AB  - OBJECTIVES: Bronchial thermoplasty (BT) can be considered in the treatment of
      severe asthma to reduce airway smooth muscle mass and bronchoconstriction. We
      hypothesized that BT may thus have long-term effects on airway dimensions and air
      trapping detectable by quantitative computed tomography (QCT). METHODS: Paired in
      and expiratory CT and inspiratory CT were acquired in 17 patients with severe
      asthma before and up to two years after bronchial thermoplasty and in 11
      additional conservatively treated patients with serve asthma, respectively. A
      fully automatic software calculated the airways metrics for wall thickness (WT),
      wall percentage (WP), lumen area (LA) and total diameter (TD). Furthermore, lung
      air-trapping was quantified by determining the quotient of mean lung attenuation
      in expiration vs. inspiration (E/I MLA) and relative volume change in the
      Hounsfield interval -950 to -856 in expiration to inspiration (RVC856-950) in a
      generation- and lobe-based approach, respectively. RESULTS: BT reduced WT for the
      combined analysis of the 2nd-7th airway generation significantly by 0.06 mm (p =
      0.026) and WP by 2.05% (p < 0.001), whereas LA and TD did not change
      significantly (p = 0.147, p = 0.706). No significant changes were found in the
      control group. Furthermore, E/I MLA and RVC856-950 decreased significantly after
      BT by 12.65% and 1.77% (p < 0.001), respectively. CONCLUSION: BT significantly
      reduced airway narrowing and air-trapping in patients with severe asthma. This
      can be interpreted as direct therapeutic effects caused by a reduction in airway
      smooth muscle mass and changes in innervation. A reduction in air-trapping
      indicates an influence on more peripheral airways not directly treated by the BT
      procedure.

PMID- 30292271
TI  - Gadoxetic acid-enhanced MRI of transient hepatic enhancement differences: Another
      cause of hypointense observation on hepatobiliary phase.
AB  - PURPOSE: To retrospectively determine the frequency, natural history and factors
      associated with the presence of transient hepatic enhancement difference showing
      hypointensity on hepatobiliary phase images of gadoxetic acid-enhanced MRI.
      MATERIALS AND METHODS: Gadoxetic acid-enhanced MRI of 125 patients (91 men; 34
      women) with transient hepatic enhancement difference were retrospectively
      reviewed. Three readers qualitatively and quantitatively evaluated MR imaging
      features and evolution at follow up. The Chi-square test, Fisher's exact test and
      Kruskall-Wallis rank test were used for statistical analysis. RESULTS: Transient
      hepatic enhancement difference were hypointense on hepatobiliary phase images in
      20 of 125 cases (16%). At univariate analysis there was association with wedge
      shape morphology (p < 0.001), size >=21 mm (p < 0.001), hyperintensity on T2
      weighted imaging (p < 0.001), restricted diffusion (p < 0.001) and previous
      treatment (p < 0.005). At multivariate analysis, the following factors were
      associated: previous treatment (p < 0.05), hyperintensity on T2-weighted imaging
      (p < 0.001) and size >=21 mm (p < 0.001). Of 12 patients with hypointense
      transient hepatic enhancement difference on hepatobiliary phase images who had
      follow-up MRI, nine showed reduction in size. CONCLUSION: Transient hepatic
      enhancement difference observations showing hypointensity on hepatobiliary phase
      images of gadoxetic acid-enhanced MRI are not infrequent and may shrink at follow
      up. They are more likely associated with size >=21 mm, hyperintensity on T2
      weighted images and previous treatment of adjacent tumor.

PMID- 30292272
TI  - Magnetic resonance elastography of healthy livers at 3.0 T: Normal liver
      stiffness measured by SE-EPI and GRE.
AB  - PURPOSE: To determine the normal liver stiffness values using magnetic resonance
      elastography (MRE) at 3.0 T and to compare spin-echo echo-planar imaging (SE-EPI)
      and gradient-recalled-echo (GRE) MRE. MATERIALS AND METHODS: This retrospective
      study included 54 living liver donors who had normal clinical and pathological
      results without underlying liver disease and underwent MRE using both SE-EPI and
      GRE at 3.0 T. Two radiologists placed four or six freehand regions of interest
      (ROI) on the elastograms and measured liver stiffness as well as the area of
      ROIs. The mean liver stiffness values and area of ROIs were compared between
      genders, among age groups, and between groups of different body mass indexes
      using the t-test and one-way analysis of variance, respectively. Interobserver
      agreement was analyzed using intraclass correlation coefficient. The mean liver
      stiffness values and area of ROIs were compared between SE-EPI and GRE using the
      paired t-test and Bland-Altman analysis. RESULTS: The liver stiffness values in
      living liver donors ranged from 1.52 to 3.12 kPa on SE-EPI and 1.51 to 2.67 kPa
      on GRE. The mean liver stiffness values did not differ significantly according to
      the gender, age, and body mass index. Measurement of liver stiffness using MRE
      showed excellent interobserver agreement on both pulse sequences. The mean value
      of liver stiffness was higher on SE-EPI (2.14 +/- 0.33 kPa) than on GRE (2.06 +/-
      0.25 kPa), and the difference was statistically significant (P < 0.05). The mean
      area of ROI was significantly larger with GRE (3387 mm2) than with SE-EPI (2691
      mm2) (P < 0.05). CONCLUSIONS: The mean liver stiffness values in living donors
      measured by SE-EPI and GRE were not affected by gender, age, or body mass index
      and showed excellent interobserver agreement. The area of ROI was larger with GRE
      than with SE-EPI.

PMID- 30292273
TI  - CT temporal subtraction method for detection of sclerotic bone metastasis in the
      thoracolumbar spine.
AB  - PURPOSE: To assess the effectiveness of a CT temporal subtraction (TS) method on
      radiologists' performance in sclerotic metastasis detection in the thoracolumbar
      spine. MATERIALS AND METHODS: 20 pairs (current and previous CTs) of standard
      dose CT and their TS images in patients with sclerotic bone metastasis and 20
      pairs (current and previous CTs) of those in patients without bone metastasis
      were used for an observer performance study. A total of 135 lesions were
      identified as the reference standard of actionable lesions (sclerotic metastasis
      newly appeared or increased in size or in attenuation). 4 attending radiologists
      and 4 radiology residents participated in this observer study. Ratings and
      locations of "lesions" determined by the observers were utilized for assessing
      the statistical significance of differences between radiologists' performances
      without and with the CT-TS images in JAFROC analysis. The statistical
      significance of differences in the reviewing time was determined by a two-tailed
      paired t-test. RESULTS: The average figure-of-merit (FOM) values for all but one
      radiologist increased to a statistically significant degree, from 0.856 without
      the CT-TS images to 0.884 with the images (P = .037). The average sensitivity for
      detecting the actionable lesions was improved from 60.7 % to 72.5% at a false
      positive rate of 0.15 per case by use of the CT-TS images. The average reading
      time with CT-TS images was significantly shorter than that without (150.6 s vs.
      166.5 s, P = .004). CONCLUSION: The use of CT-TS would improve the observer
      performance for the detection of the sclerotic bone metastasis in the
      thoracolumbar spine.

PMID- 30292274
TI  - Metal artifact reduction techniques in musculoskeletal CT-imaging.
AB  - It is known that metal artifacts can be reduced by modifying standard acquisition
      and reconstruction, by modifying projection data and/or image data and by using
      virtual monochromatic imaging extracted from dual-energy CT. In this review we
      focus on the origin of metal artifacts, technical background of commercially
      available metal artifact reduction (MAR) algorithms and the value of dual-energy
      CT and MAR software for different metal hardware in current clinical practice.
      Virtual monochromatic imaging reduces beam-hardening artifacts, where metal
      artifact reduction software effectively reduces artifacts caused by extensive
      photon-starvation. Both techniques have their advantages and disadvantages, and
      the combination of both techniques is often but not always the best solution
      regarding metal artifact reduction. Advances in prosthetic imaging are reinforced
      by advances in prosthetic design. Providing implant specific information prior to
      scanning is important in order to adjust the metal artifact reduction approach,
      minimize artifacts and optimize image quality and diagnostic value of CT.

PMID- 30292275
TI  - Validation of water-fat MRI and proton MRS in assessment of hepatic fat and the
      heterogeneous distribution of hepatic fat and iron in subjects with non-alcoholic
      fatty liver disease.
AB  - BACKGROUND: Research studies demonstrated pathologic lesions were unevenly
      distributed in patients with non-alcoholic fatty liver disease (NAFLD) and non
      alcoholic steatohepatitis. As hepatic steatosis occurs prior to steatohepatitis
      and other late stage liver conditions, the distribution pattern of hepatic fat
      and iron concentration should be investigated to prevent sampling variability.
      The first purpose of this study was to perform comparison and validation of in
      house hepatic fat measurements using water-fat MRI and MRS. The second objective
      was to quantify hepatic fat-fraction and T2* values in left and right liver lobes
      using water-fat MRI. METHOD: Fifty-four non-alcoholic adults (27 NAFLD, age: 42.8
      +/- 11.8), 27 non-NAFLD, age: 45.5 +/- 11.2) and 46 non-alcoholic teenagers (23
      NAFLD (age: 15.4 +/- 2.6), 23 non-NAFLD (age: 13.9 +/- 2.3) were recruited. All
      participants underwent chemical shift water-fat MRI and 1H MRS at 3 T. Hepatic
      steatosis was defined by intrahepatic triglyceride more than the threshold of
      5.56% using MRS (clinical reference) and non-alcoholic was defined by alcohol
      ingestion of no more than 30 g and 20 g per day for male and female respectively.
      Hepatic fat-fractions in left and right liver lobes were measured using regions
      of-interest (ROIs) approach. Three ROIs were drawn on the fat-fraction images and
      duplicated on to the co-registered T2* images at the inferior right, superior
      right and superior left liver lobes. Comparison and validation of water-fat MRI
      and MRS were performed using intraclass correlation coefficient (ICC) and Bland
      Altman plot. Hepatic fat-fraction and T2* measured from the ROIs were compared
      using repeated measures ANOVA. Independent t-test was used for between groups
      analysis. RESULTS: Statistical analysis indicated good correlation (R = 0.987)
      and agreement (ICC = 0.982) between MRS and water-fat MRI in hepatic fat
      measurements. Results indicated that hepatic fat was significantly higher in the
      right lobe compared to the left in NAFLD adults (p < 0.001) and NAFLD teenagers
      (p < 0.001). For T2*, significant difference between left and right lobes was
      observed in NAFLD adults (p < 0.001) and non-NAFLD adults (p < 0.001) but not in
      teenagers. CONCLUSION: Hepatic fat measurements using MRS and water-fat MRI are
      statistically equivalent. In subjects with NAFLD regardless of their age, hepatic
      fat is stored preferentially in the right live lobe probably due to the
      streamline of blood flow to the right liver. T2* value is significantly higher in
      the right liver lobe in adults but not in the teenagers regardless of their
      hepatic fat contents probably due to the longer time span of hepatic iron
      accumulation.

PMID- 30292276
TI  - Crossed cerebellar diaschisis in post-treatment glioma patients: A comparative
      study of arterial spin labelling and dynamic susceptibility contrast.
AB  - OBJECTIVES: To assess crossed cerebellar diaschisis (CCD) in post-treatment
      glioma patients, and to compare the performance of arterial spin labelling (ASL)
      and dynamic susceptibility contrast (DSC) in detecting CCD. METHODS AND
      MATERIALS: This retrospective study included 130 patients who had both DSC and
      ASL. Among them, 16 had underwent fluorine-18 fluorodeoxyglucose positron
      emission tomography/computed tomography (18F-FDG PET/CT). We investigated the
      relationship between CCD and the location and size of supratentorial lesions, and
      compared PET diagnostic performance with that of ASL and DSC. We assessed the
      inter-methods agreement for ASL and DSC, and performed quantitative analysis by
      calculating the asymmetry index (AI) between bilateral cerebellum and exploring
      how the AI values for ASL-CBF, DSC-rCBF, and DSC-rCBV maps correlated with each
      other. RESULT: Supratentorial lesions affecting the corona radiata (P < 0.001),
      basal ganglia (P < 0.001), and insula (P = 0.046) were significantly associated
      with the occurrence of CCD. Lesion size was significantly larger (P = 0.005) in
      the CCD positive group. With PET as a reference, ASL-CBF and DSC-rCBF maps
      exhibited the best diagnostic performance compared with the other DSC-generated
      maps (diagnostic accuracy = 83.3% for both, area under curve (AUC) of ASL =
      0.967, AUC of rCBF = 0.983), although differences were not statistically
      significant. The kappa value for the inter-methods (ASL and DSC) agreement in
      detecting CCD was 0.893, while the degree of perfusion asymmetry was more
      significant in ASL- than DSC-generated maps. Bland-Altman plots showed that the
      AI for ASL-CBF was moderately correlated with those for DSC-rCBF and DSC-rCBV.
      CONCLUSIONS: CCD can present in post-treatment glioma patients and is detectable
      on MR-perfusion images including ASL-CBF, DSC-rCBF, and DSC-rCBV maps.

PMID- 30292277
TI  - Myocardial T1 and T2 mapping in severe aortic stenosis: Potential novel insights
      into the pathophysiology of myocardial remodelling.
AB  - PURPOSE: Severe aortic stenosis (AS) is known to be associated with substantial
      myocardial remodelling, leading to diffuse myocardial fibrosis (DMF). Native
      myocardial T1 is emerging as a novel imaging biomarker for the non-invasive
      assessment of DMF. In contrast, no studies exist elucidating changes of
      myocardial T2 reflecting myocardial oedema in the presence of AS. The purpose of
      the present study was to combine native T1 and T2 mapping in order to
      characterize myocardial tissue changes in the setting of severe AS. METHODS:
      After obtaining ethical approval and informed consent, a total of 26
      prospectively selected patients with severe AS (13 women, mean age 81 +/- 7
      years) and 17 healthy controls (12 women, mean age 63 +/- 6 years) underwent
      cardiac magnetic resonance (CMR) imaging on a clinical 3 T scanner. The CMR
      protocol included a native Modified Look-Locker (MOLLI) T1 mapping and a Gradient
      Spin Echo (GraSE) T2-mapping sequence in three short-axis slices and one long
      axis view. After segmentation, myocardial T1 and T2 values were averaged over the
      entire myocardium. Statistical analysis was performed using Wilcoxon sum-rank
      test, Welch's independent t-test and Pearson's correlation coefficient. RESULTS:
      Global native myocardial T1 was significantly increased in AS patients when
      compared to controls (1305 +/- 39 vs. 1272 +/- 21 ms, p = .005). Similarly, mean
      myocardial T2 was significantly elevated in AS patients (51 +/- 4 vs. 46 +/- 2
      ms, p < .001) and showed a strong correlation with native T1 (r = .60, p < .001).
      An overlap was observed between T1 of both groups, whereas T2 discriminated
      nearly perfectly between the two groups (area under the curve in ROC analyses:
      0.76 for T1, 0.87 for T2). CONCLUSIONS: Patients with severe AS exhibit
      significantly elevated native myocardial T1, which has previously been shown to
      correlate with the amount of myocardial collagen. Adding to this evidence, the
      present study is the first to show that native T1 and T2 are both significantly
      elevated and correlated in AS patients, pointing towards a potential role of
      oedematous/inflammatory processes in the pathophysiology of myocardial
      remodelling associated with AS.

PMID- 30292278
TI  - Single extracorporeal shock-wave lithotripsy for proximal ureter stones: Can CT
      texture analysis technique help predict the therapeutic effect?
AB  - PURPOSE: To explore whether the computed tomography texture analysis (CTTA)
      technique can help predict the curative effects of a single extracorporeal shock
      wave lithotripsy (ESWL) for proximal ureteral stones. MATERIALS AND METHODS: In
      all, 100 patients with proximal ureteral stone underwent non-enhanced multi
      detector computed tomography (MDCT) before ESWL. The patients were divided into
      success and failure groups. Success of ESWL was defined as the patients being
      stone-free or having residual stone fragments of <=2 mm. Traditional
      characteristics, such as stone size, body mass index (BMI), and skin-to-stone
      distance (SSD), and CTTA metrics, such as the mean Hounsfield unit (HU) density,
      entropy, kurtosis, and skewness, were analyzed and compared between two groups by
      univariate and multivariate logistic regression analyses. Receiver operating
      characteristic (ROC) curves were generated to determine Youden index-based cutoff
      values. RESULT: Failure of stone removal was observed in 36 patients (36%). Stone
      height, stone cross-sectional diameter, largest cross-sectional area, stone
      volume, stone density (mean HU), and CTTA metrics (kurtosis and entropy) were the
      significant independent predictors of ESWL success on univariate analysis (p <
      0.05). On multivariate analysis, mean HU, skewness, and kurtosis were shown to be
      significant predictors of ESWL success (p < 0.05). In subgroup analysis based on
      the cutoff value of mean stone density (HU = 857), the only significant
      independent factor associated with both subgroups was kurtosis (p < 0.05).
      CONCLUSIONS: As a quantitative analysis method, CTTA may be helpful in selecting
      appropriate ESWL patients. High kurtosis and low mean HU values simultaneously
      indicate a relatively higher ESWL success rate.

PMID- 30292279
TI  - CT texture analysis can be a potential tool to differentiate gastrointestinal
      stromal tumors without KIT exon 11 mutation.
AB  - OBJECTIVE: To evaluate CT texture analysis as a tool to differentiate
      gastrointestinal stromal tumors (GISTs) without KIT exon 11 mutation. MATERIALS
      AND METHODS: This study consisted of a study group of 69 GISTs and a validation
      group of 17 GISTs. Clinical information of the patients were collected and
      analyzed. Two-dimensional and three-dimensional texture analysis was performed.
      The textural parameters were evaluated in the study group and were validated in
      the validation group. The repeatability of the textural parameters on the single
      region of interest (single-ROI), double-ROI, and whole volume of interest (whole
      VOI) was analyzed. The independent predictor for the GIST genotypes was analyzed
      with logistic regression models. The support vector machine (SVM) classifiers
      were also trained and 6-fold cross validation ROC curves were computed.
      Subjective heterogeneity scores of each lesion on enhanced CT images were given
      by radiologists and the corresponding difference of the heterogeneity rating was
      evaluated. RESULTS: The non-gastric location, lower CD34_stain level and higher
      textural parameter standard Deviation (stdDeviation) were associated with the
      GISTs without KIT exon 11 mutation in the study group. The cross validation SVM
      classifiers achieved with combination of stdDeviation, anatomic location and
      CD34_stain level demonstrated medium to good prediction efficiency (AUC = 0.864
      0.904) regarding the GIST genotypes. The stdDeviation was an independent
      predictor of GISTs without KIT exon 11 mutation, and had a medium correlation
      with the GIST genotypes in the study group (AUC = 0.726-0.750). The stdDeviation
      showed good performance (AUC = 0.904-0.962) when validated in the validation
      group. The double-ROIs improved the performances of single-ROIs, decreasing the
      variances of single-ROIs brought by section-selection, and demonstrating
      excellent agreements between ROIs and whole-VOI. Subjective heterogeneity scores
      had no statistically significant differences between GIST genotypes. CONCLUSION:
      CT texture analysis can potentially help to differentiate GISTs without KIT exon
      11 mutation from those GISTs with KIT exon 11 mutation on enhanced CT images.

PMID- 30292280
TI  - Computed tomography findings of arc-welders' pneumoconiosis: Comparison with
      silicosis.
AB  - OBJECTIVE: Arc-welders' pneumoconiosis (AWP) is a less fibrogenic pneumoconiosis
      with radiographic shadows that can improve after isolation from dusty
      environments. Therefore, early diagnosis is important. However, the exact role of
      chest radiograph and computed tomography (CT) for diagnosing AWP is not fully
      understood. This study was performed to assess the CT appearance of AWP using
      semi-quantitative methods and to compare the findings with those of silicosis.
      The profusion of pulmonary abnormality on chest radiograph were also compared
      with the semi-quantitative CT score. MATERIALS AND METHODS: Sixty-six patients
      with clinically diagnosed AWP were included and compared with 33 patients with
      silicosis. The CT images were interpreted according to the International
      Classification of HRCT for Occupational and Environmental Respiratory Diseases
      (ICOERD). Data on the profusion score by chest radiograph were also compared with
      CT score. RESULTS: Ill-defined centrilobular nodules, ground-glass opacity (GGO)
      and centrilobular branching opacity were more frequently observed (p = 0.0031) in
      AWP, whereas well-defined rounded opacity (p < 0.0001), progressive massive
      fibrosis (p < 0.0001), and mediastinal lymphadenopathy (p < 0.0001) were more
      frequently observed in silicosis. Regarding lung nodules, there was a high
      correlation between the ICOERD and CXR profusion scores in silicosis, but CXR
      underestimated AWP. CONCLUSION: Ill-defined centrilobular nodules, GGO and
      centrilobular branching opacity were more frequently observed in AWP than
      silicosis. Because these findings are difficult to detect by chest radiograph, CT
      should be considered for the assessment of patients with suspected AWP.

PMID- 30292281
TI  - Outcomes and Safety of Transcatheter Aortic Valve Implantation With and Without
      Routine Use of Transesophageal Echocardiography.
AB  - Transesophageal echocardiography (TEE) has been extensively used historically for
      Transcatheter aortic valve implantation (TAVI) but focus is shifting from routine
      use of TEE and general anesthesia to "as needed" use. We evaluated patients who
      had TAVI in our institution from September 2012 to February 2017. Decision for
      implantation and use of TEE during procedure was made by the structural heart
      team on a case-to-case basis, based on FDA approved indications. Data including
      procedural details, length of stay and rehospitalizations were obtained from all
      patients. TAVI was performed on 178 patients during the study period of which 104
      of 178 had TEE during TAVI. Baseline characteristics were fairly comparable in
      both groups. Similar proportion of self-expanding and balloon expanding valves
      were deployed. Patients in TEE group had longer overall procedure time (107
      minute vs 83 minute, p = 0.0002) and longer length of stay (5.01days vs 2.49days,
      p < 0.0001). Echocardiographic study postprocedure showed similar incidence of
      paravalvular leak and similar gradients and velocities across aortic valve. Rates
      of 30-day readmissions were similar in both groups. In conclusion, in this single
      center retrospective analysis-TAVI without the 'routine use' of TEE was
      comparable with those done with TEE guidance in terms of periprocedural
      complications and 30-day readmissions. Overall procedure length and length of
      stay was predictably higher in the TEE group.

PMID- 30292282
TI  - Effects of Gestational Age on Early Survivability in Neonates With Hypoplastic
      Left Heart Syndrome.
AB  - Prematurity increases pre- and postoperative mortality in children with
      congenital heart disease. There are no large, multicentered, studies that have
      evaluated this relation specifically in neonates with hypoplastic left heart
      syndrome (HLHS). We sought to determine the impact of gestational age (GA) on
      survival to Stage 1 palliation surgery and hospital discharge in infants with
      HLHS. We reviewed data from 1,913 neonates with HLHS born at or transferred to a
      Vermont Oxford Network expanded member hospital in the United States from 2009 to
      2014. Demographic, diagnostic, and surgical codes, and outcome data within the
      Vermont Oxford Network database were used to determine the effect of GA and birth
      weight on survival to Stage 1 palliation surgery and hospital discharge. Risk
      models were developed controlling for common confounders to determine the
      relative risk of GA on the observed outcomes. These data demonstrate that, when
      compared with 39-week infants, those born at earlier GA were less likely to
      survive until surgery; <34 weeks adjusted risk ratio (ARR) for survival: 0.47
      (95% confidence interval 0.37 to 0.60), 34 to 35 weeks ARR 0.73 (0.62 to 0.87),
      and 36 to 37 weeks ARR 0.88 (0.83 to 0.94). Higher GA also positively correlated
      with survival to hospital discharge, although there was no difference in 34 to 35
      week infants and 36 to 37-week infants. In conclusion, these data show that GA
      was an independent risk factor for survival to Stage 1 palliation surgery and
      survival to hospital discharge. However, there is no significant difference in
      survival to hospital discharge between infants born in 34 to 37 weeks gestation.

PMID- 30292283
TI  - Preface.

PMID- 30292284
TI  - The Schistosoma mansoni lipidome: Leads for immunomodulation.
AB  - Schistosoma mansoni is a parasitic helminth that infects millions of people
      mostly in tropical parts of the world. Different life cycle stages of S.mansoni,
      that infect or develop in the human host, promote distinct immune responses and
      are known for their ability to modulate host immune responses. However, the
      molecular mechanisms through which the parasites interact with, and modulate the
      host immune system remain incompletely understood. Despite the well-known ability
      of various lipids to modulate immune responses, a comprehensive analysis of the
      lipidome of the different life cycle stages has not been performed. Using three
      complementary MS-based platforms to detect and quantify around 350 lipid species,
      we here characterized the lipid profiles of S. mansoni cercariae, worms and eggs,
      as well as extracts and excretory/secretory (ES) products of different life cycle
      stages of S. mansoni. We identified life cycle stage specific signatures of lipid
      classes of which cercariae were found to have the most distinct profile.
      Moreover, we detected several immunolomodulatory oxylipids in the different life
      cycle stages. Specifically, prostaglandins were found to be most highly enriched
      in egg preparations, while resolvins were specifically detected in cercariae.
      Together, the generation of this detailed lipid database of the different life
      cycle stages of S. mansoni will not only be important for a better understanding
      of the biology of the parasite itself but also of host-parasite interactions and
      how that could result in immunomodulation.

PMID- 30292285
TI  - Serially coupled reversed phase-hydrophilic interaction liquid chromatography
      tailored multiple reaction monitoring, a fit-for-purpose tool for large-scale
      targeted metabolomics of medicinal bile.
AB  - The acquisition of high-quality quantitative dataset is the prerequisite for
      large-scale targeted metabolomics. However, the goal is usually dampened by the
      complexity of the biological matrices in terms of structural diversity,
      concentration span, and polarity range. We attempted herein to propose an
      analytical approach being able to circumvent these technical obstacles, and
      medicinal bile was employed as a proof of concept. In the liquid chromatography
      (LC) domain, reversed phase LC and hydrophilic liquid interaction chromatography
      were coupled in series, namely RPLC-HILIC, to yield appropriate chromatographic
      behavior for each component regardless of the polarity. In-depth chemical
      characterization and widely quantitative analysis were successively conducted in
      the mass spectrometry (MS) domain. Hybrid ion trap-time of flight MS was jointly
      deployed with hybrid triple quadrupole-linear ion trap MS for metabolite
      searching because of their orthogonal natures. Afterwards, a tailored MRM
      strategy that integrated online parameter optimization, ion intensity tailoring,
      and scheduled monitoring, was subsequently constructed to accomplish
      comprehensive quantitation although authentic compounds weren't involved and
      concentration span was quite large. Calibration curve was constructed for each
      detected identity by preparing and serially diluting the universal metabolome
      standard (UMS) solution that merged chemical information from all bile samples.
      Quasi-contents of 164 components including bile acids, sterols, eicosanoids,
      amino acids, lipids, flavonoids, and so forth, were gained by applying those
      regressive calibration curves and replaced the role of peak areas to serve as the
      variables for multivariate statistical analysis. In particular, the concentration
      ratio between tauroursodeoxycholic acid (TUDCA) and taurohyodeoxycholic acid
      (THDCA) that were exactly co-eluted as a single peak was calculated from the
      intensity specific value of m/z 498 > 80 over 498 > 124. Different metabolome
      occurred among various animal bile samples, and significant variations were also
      observed for different batches of bear bile powders. Bile acids acted as the
      indicative components in either discrimination. Overall, RPLC-HILIC-tailored MRM
      enabled quantitative metabolome profiling of medicinal bile and was thereby a
      promising analytical tool for large-scale targeted metabolomics.

PMID- 30292286
TI  - Dark matter in host-microbiome metabolomics: Tackling the unknowns-A review.
AB  - The "dark matter" in metabolomics (unknowns) represents an exciting frontier with
      significant potential for discovery in relation to biochemistry, yet it also
      presents one of the largest challenges to overcome. This focussed review takes a
      close look at the current state-of-the-art and future challenges in tackling the
      unknowns with specific focus on the human gut microbiome and host-microbe
      interactions. Metabolomics, like metabolism itself, is a very dynamic discipline,
      with many workflows and methods under development, both in terms of chemical
      analysis and post-analysis data processing. Here, we look at developments in the
      mutli-omic analyses and the use of mass spectrometry to investigate the exchange
      of metabolites between the host and the microbiome as well as the environment
      within the microbiome. A case study using HuMiX, a microfluidics-based human
      microbial co-culture system that enables the co-culture of human and microbial
      cells under controlled conditions, is used to highlight opportunities and current
      limitations. Common definitions, approaches, databases and elucidation techniques
      from both the environmental and metabolomics fields are covered, with
      perspectives on how to merge these, as the boundaries blur between the fields.
      While reflecting on the number of unknowns remaining to be conquered in typical
      complex samples measured with mass spectrometry (often orders of magnitude above
      the "knowns"), we provide an outlook on future perspectives and challenges in
      elucidating the relevant "dark matter".

PMID- 30292287
TI  - Metabolomics studies on db/db diabetic mice in skeletal muscle reveal effective
      clearance of overloaded intermediates by exercise.
AB  - Type 2 diabetes mellitus (T2DM) is characterized by hyperinsulinemia,
      hyperglycemia and insulin resistance, which correlated with high mortality
      worldwide. Exercise is one of the effective lifestyle interventions in
      maintaining blood glucose level in the normal range and lowering risk factors.
      Metabolomics approaches are powerful tools in systematic study of overall
      metabolic changes in response to disease or interventions. In this study, mass
      spectrometry-based metabolomics studies were performed to investigate the
      regulatory effect of moderate intensity of exercise on db/db diabetic mice in
      skeletal muscle. Both liquid chromatography-mass spectrometry (LC-MS) and gas
      chromatography-mass spectrometry (GC-MS) have been carried out to monitor a wide
      range of regulated metabolites. Ninety-five metabolites were identified which
      contributing to the discrimination of db/m  + control and db/db diabetic mice.
      The regulatory effects of exercise on these metabolites were mainly focusing on
      attenuating the levels of long-chain fatty acids (C14 to C18) and medium-to long
      chain acylcarnitines (C12 to C18), indicated that exercise might play a positive
      role in inhibiting the accumulation of excessive lipids, which is positively
      related to insulin resistance. In addition, uric acid, which is a risk factor for
      inflammation, cardiovascular complications, and fatty liver in diabetic patients,
      together with its intermediates (such as inosinic acid, hypoxanthine, etc.) in
      purine metabolism pathway, were also substantially down regulated after exercise,
      indicating exercise might also be protective against hyperuricemia related risks
      in T2DM. These findings reveal that moderate intensity of exercise might play a
      positive role in improving the efficiency of lipid metabolism in skeletal muscle
      and meanwhile enhancing uric acid clearance to prevent lipid accumulation, which
      might contribute to improved body fitness and body muscle composition.

PMID- 30292288
TI  - Metabolomics study of early metabolic changes in hepatic HepaRG cells in response
      to rosemary diterpenes exposure.
AB  - Rosemary diterpenes have demonstrated diverse biological activities, such as anti
      cancer, antiinflammatory, as well as other beneficial effects against
      neurological and metabolic disorders. In particular, carnosic acid (CA), carnosol
      (CS) and rosmanol (RS) diterpenes have shown interesting results on anti-cancer
      activity. However, little is known about the toxic effects of rosemary diterpenes
      at the concentrations needed to exert their antiproliferative effect on cancer
      cells. In our study, CA, CS and RS exhibited a concentration-dependent effect on
      cell viability of two human colon cancer cell lines (HT-29 and HCT116) after 24 h
      exposure. HT-29 cell line was more resistant to the inhibitory effect of the
      three diterpenes than HCT116 cell line. Among the three diterpenes, RS exerted
      the strongest effect in both cell lines. To investigate the hepatotoxicity of CA,
      CS and RS, undifferentiated and differentiated HepaRG cells were exposed to
      increasing concentrations of the diterpenes (from 10 to 100 MUM). Differentiated
      cells were found to be more resistant to the toxic activity of the three
      diterpenes than undifferentiated HepaRG, probably related to a higher detoxifying
      function of differentiated HepaRG cells compared with the undifferentiated cells.
      The metabolic profiles of differentiated HepaRG cells in response to CA, CS and
      RS were examined to determine biochemical alterations and deepen the study of the
      effects of rosemary phenolic diterpenes at molecular level. A multiplatform
      metabolomics study based on liquid- and gas-chromatography hyphenated to high
      resolution mass spectrometry revealed that rosemary diterpenes exerted different
      effects when HepaRG cells were treated with the same concentration of each
      diterpene. RS revealed a greater metabolome alteration followed by CS and CA, in
      agreement with their observed cytotoxicity. Metabolomics provided valuable
      information about early events in the metabolic profiles after the treatment with
      the investigated diterpenes from rosemary.

PMID- 30292289
TI  - An integrated method for direct interrogation of sphingolipid homeostasis in the
      heart and brain tissues of mice through postnatal development up to reproductive
      senescence.
AB  - Development of rapid metabolomic methods poised for pathway discovery is expected
      to facilitate the identification of therapeutic candidates in the metabolomic
      approach to translational medicine. Using sphingolipid homeostasis as a
      prototype, we present herein an integrated method to facilitate a fast
      interrogation of altered sphingolipid (and phospholipid) metabolism associated
      with perturbed endolysosomal functions in mammalian systems. Constructed upon
      high performance liquid chromatography coupled to mass spectrometry, this method
      allows semi-quantitative measurements of more than 300 individual species within
      20 min. The method was applied to investigate cardiac- and neural-specific
      developmental changes in sphingolipid regulation from the postnatal stage to
      reproductive senescence in mice, revealing that endogenous lysobisphosphatidic
      acids and specific complex glycosphingolipids are tightly co-regulated to foster
      concerted reductions in sphingolipid levels at distinct stages of postnatal
      development. Our lipidomic data suggest that such changing regulatory patterns in
      sphingolipid homeostasis is attributed to differential endolysosomal degradation
      of complex sphingolipids, which may be critical in ensuring efficient
      sphingolipid catabolism and organismal health at each stage of postnatal
      development.

PMID- 30292290
TI  - A sensitive, high-throughput LC-MS/MS method for measuring catecholamines in low
      volume serum.
AB  - A robust, sensitive, high-throughput method for the detection and quantification
      of catecholamines in serum, including dopamine, 5-methoxytryptamine, tyramine,
      phenylethylamine (PEA), epinephrine (EPI), norepinephrine (NE), metanephrine
      (MN), and normetanephrine (NMN) is described. It is based on liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) in a positive scheduled
      multiple reaction monitoring (MRM) mode. Key to the success of the method is the
      inclusion of an amine derivatization step, using phenylisothiocyanate (PITC),
      prior to liquid chromatographic separation of the targeted analytes on a C18
      reversed-phase column. Mass spectrometric conditions, e.g., characteristic
      fragmentations and quantification transitions were also optimized to obtain
      maximum sensitivity and specificity. The limits of detection for all the target
      analytes are in the low nanomolar range. The recovery rates of spiked serum
      samples with three different concentration levels, i.e., low, medium, and high,
      are in the range of 93.2%-113% with satisfactory precision values of less than
      10.9%. This method was successfully applied to determine the concentrations of
      dopamine, 5-methoxytryptamine, tyramine, PEA, EPI, NE, MN, and NMN in multiple
      human serum samples, with results matching closely those reported in the
      literature. Comparisons to other reported methods for measuring catecholamines
      indicates this new approach requires 10-20X less volume, making it ideal for
      targeted metabolomics studies with volume-limited samples. The method has been
      adapted to a 96-well plate format and has allowed the quantitative determination
      of catecholamines in more than 800 serum samples on a single instrument in just
      nine days.

PMID- 30292291
TI  - Software-aided quality control of parallel reaction monitoring based quantitation
      of lipid mediators.
AB  - We characterized the performance of a micro-flow LC-ESI-MS2 approach to analyze
      lipid mediators (LMs) and polyunsaturated fatty acids (PUFA) that was optimized
      for SPE free lipid extraction. Tandem mass spectrometry was exclusively performed
      in parallel reaction monitoring (PRM) mode using TOF and Orbitrap analyzers. This
      acquisition strategy allowed in addition to quantitation by specific quantifier
      ions to perform spectrum comparisons using full MS2 spectra information of the
      analyte. Consequently, we developed a dedicated software SpeCS that allows to 1)
      process raw peak lists, 2) generate customized spectral libraries, 3) test
      specificity of quantifier ions and 4) perform spectrum comparisons. The dedicated
      scoring algorithm is based on signal matching and Spearman's rank correlation of
      intensities of matched signal. The algorithm was evaluated in respect of its
      specificity to distinguish structural related LMs on both instrument platforms.
      We show how high resolution mass spectrometry is beneficial to distinguish co
      eluted LM isomers and provide a generalized quality control procedure for PRM.
      The applicability of the approach was evaluated analyzing the lipid mediator
      response during M. tuberculosis infection in the mouse lung.

PMID- 30292292
TI  - Isotope-labeling derivatization with 3-nitrophenylhydrazine for LC/multiple
      reaction monitoring-mass-spectrometry-based quantitation of carnitines in dried
      blood spots.
AB  - Carnitines are diagnostic biomarkers of fatty acid oxidation defects and organic
      acidemias. Quantitative measurements of various carnitines in dried blood spot
      (DBS) have potential use in remote health applications for disease diagnosis and
      epidemiological surveillance. To provide an improved LC/multiple-reaction
      monitoring (MRM)-MS method for quantitation of carnitines in DBS, 3
      nitrophenylhydrazine (3NPH) was tested as a high-efficiency chemical isotope
      labeling reagent for pre-analytical derivatization of 24 routinely-analyzed
      species. Reaction conditions were optimized and carnitine structural isomers were
      separated by reversed-phase LC with positive-ion MRM/MS detection, giving on
      column lower LOQs of sub- to low-femtomole levels. 13C6-3NPH was used to produce
      13C6- or 13C12-labeled derivatives of the mono- and di-carboxylic carnitines in a
      "one-pot" reaction. These labeled analogues were used as stable isotope-labeled
      internal standards to compensate for possible ESI matrix effects. Combined with
      an optimized, two-step procedure for the extraction of carnitines from DBS, this
      isotope-labeling derivatizaiton - LC/MRM-MS method provided good linearity, high
      precision (intra-day CVs of <=7.8% and inter-day CVs of <=8.8%) and high accuracy
      (three levels of standard substances spiked in, with recoveries of 86.9%-109.7%)
      quantitation of carnitines in three sets of DBSs on cellulose or cotton filter
      paper. This method was then applied to determine the concentration changes of the
      analytes in the DBSs under two stability-testing regimes: 1) a one-time 4-h
      sunlight exposure and 2) a set of cycled temperature transitions (-20  degrees C
      for 2 days, 40  degrees C for 2 days, and back to -20  degrees C for 2 additional
      days). All of the carnitines showed good stabilities under the first testing
      condition. Under the second testing condition, free carnitine showed
      concentration increases of 9.3%-16.1%; acetyl carnitine, 3-OH butyryl carnitine,
      and malonyl carnitine showed concentration decreases of 12.2%-17.3%, 12.9%-17.1%
      and 10.7%-15.3%, respectively, and other 20 acyl carnitines showed concentration
      changes of <10% in three sets of DBSs on cellulose or cotton filter paper. These
      preliminary stability-testing results indicate a need to more systematically
      investigate the effects of various environmental conditions on the chemical
      stabilities of carnitines in DBS specimens if this sampling method is to be used
      in remote health applications.

PMID- 30292293
TI  - Targeted metabolomics in bladder cancer: From analytical methods development and
      validation towards application to clinical samples.
AB  - Bladder cancer constitutes the ninth most common cancer worldwide and, despite
      continuous development of new diagnostic approaches, the thirteenth leading cause
      of global cancer mortality. In our previous untargeted urine metabolomic
      investigation, seventeen metabolites were found to be statistically
      differentiating bladder cancer patients and healthy volunteers. Therefore, the
      main goal of this study was to develop and validate an analytical method for
      simultaneous quantitative determination of those metabolites using reversed phase
      high-performance liquid chromatography coupled with triple quadrupole mass
      spectrometry technique (RP-HPLC-QQQ/MS). Different chromatographic conditions, as
      well as various sample treatment procedures were tested in order to provide the
      best separation and the lowest limit of quantification (LOQ) values for studied
      compounds. The validation was performed according to the Food and Drug
      Administration guidelines (FDA). The limit of determination (LOD) and the LOQ
      values were in the range of 0.21-10.51 ng/ml and 0.69-35.02 ng/ml, respectively.
      The concentration range of compounds was developed between 2.5 and 12500 ng/ml.
      Only one compound (trimethyllysine) showed a significant matrix effect (61%) and
      consequently low process efficiency (64%). Overall, developed method presented
      recovery and precision values within the ranges proposed by FDA guidelines. The
      optimized and validated method was applied to urine samples obtained from 40
      patients with bladder cancer and 40 healthy volunteers matched according to ones
      of the most important risk factors for developing urinary bladder tumors, e.i.
      age, gender and BMI. Afterwards, statistical analysis was provided by the use of
      Student's t-test or U-Mann Whitney test. The developed method was sensitive,
      selective and reproducible to be applied for the quantification of metabolites in
      the investigation of urine samples. As a consequence, ten out of previously
      chosen seventeen compounds, participating in different metabolites' pathways (gut
      floral metabolism, RNA degradation, purine metabolism, etc.), were found to be
      statistically significantly different in the urine concentration (p < 0.05)
      between cancer and control groups.

PMID- 30292294
TI  - Simultaneous determination of tryptophan and its 31 catabolites in mouse tissues
      by polarity switching UHPLC-SRM-MS.
AB  - Tryptophan (TRP) and its catabolites have attracted a lot of attention because of
      their clinical significance to human health. Recently, microbiome-gut-brain axis
      was found to have links to many diseases based on the imbalance of TRP
      catabolism. By using ultra-high performance liquid chromatography coupled to
      electrospray ionization triple quadrupole mass spectrometry, we present a rapid,
      robust and comprehensive method to determine 31 TRP catabolites covering three
      major pathways - kynurenic, serotonergic and bacterial degradation - within 5
      min. Polarity switching was employed to analyze catabolites in both ionization
      modes simultaneously for greatly improved analytical throughput. The intra-day
      and inter-day precision were 0.5-15.8% and 1.5-16.7%, respectively. Accuracy was
      between 75.8 and 126.9%. The developed method was applied to study the tissue
      level of TRP catabolites in the liver, ileum, ileal contents, brain and plasma
      samples from 8 mice, and clear differences in the distribution of TRP catabolites
      were observed in different tissues. Ratios of key catabolites to TRP were used to
      evaluate the activities of specific enzyme and pathway in respective tissues.
      This method has potential in high throughput analysis of TRP catabolites in
      biological matrices, which can facilitate understanding the influence of TRP
      catabolites on microbiome-gut-brain axis and on human health.

PMID- 30292296
TI  - Assessment of chemical equivalence in herbal materials using chromatographic
      fingerprints by combination of three similarity indices and three-dimensional
      kernel density estimation.
AB  - An intuitive and practical way to control chemical equivalence of secondary
      metabolites in herbal materials based on chromatographic fingerprints deserves a
      thorough discussion, yet it is relatively unexplored. For the first time, we
      propose a mixture of three similarity indices, the congruence coefficient, the
      average of the peak area ratios, and the larger value between the maximum peak
      area ratio and the reciprocal of the minimum peak area ratio, to make up for the
      weak points of some widely used similarity indices and to evaluate the chemical
      equivalence of two fingerprints from various perspectives. The three similarity
      values are fed into a three-dimensional kernel density estimation to determine
      the quality of herbal materials. This estimation enables precise detection of
      anomalies in the absence of prior quality determination experience. Forty
      Atractylodes samples similar in appearance and indiscriminately used for medical
      purposes were used to demonstrate the effectiveness of the developed approach.
      After a reference sample was postulated, a quality assessment of the 40 samples
      was performed using the three similarity values and the estimated kernel density.
      The samples that were judged by the developed approach to be of good quality were
      compared with those chosen by the most popular approach using decision criterion
      of a single similarity index. The benefits of the proposed approach were evident
      in that the qualified samples had the composition ratio and individual
      concentrations of multi-components closer to those of the reference in general,
      and their inter-sample deviation was significantly smaller.

PMID- 30292295
TI  - Towards enhanced metabolomic data analysis of mass spectrometry image:
      Multivariate Curve Resolution and Machine Learning.
AB  - Large amounts of data are generally produced from mass spectrometry imaging (MSI)
      experiments in obtaining the molecular and spatial information of biological
      samples. Traditionally, MS images are constructed using manually selected ions,
      and it is very challenging to comprehensively analyze MSI results due to their
      large data sizes and highly complex data structures. To overcome these barriers,
      it is obligatory to develop advanced data analysis approaches to handle the
      increasingly large MSI data. In the current study, we focused on the method
      development of using Multivariate Curve Resolution (MCR) and Machine Learning
      (ML) approaches. We aimed to effectively extract the essential information
      present in the large and complex MSI data and enhance the metabolomic data
      analysis of biological tissues. Multivariate Curve Resolution-Alternating Least
      Squares (MCR-ALS) algorithm was used to obtain major patterns of spatial
      distribution and grouped metabolites with the same spatial distribution patterns.
      In addition, both supervised and unsupervised ML methods were established to
      analyze the MSI data. In the supervised ML approach, Random Forest method was
      selected, and the model was trained using the selected datasets based on the
      distribution pattern obtained from MCR-ALS analyses. In the unsupervised ML
      approach, both DBSCAN (Density-based Spatial Clustering of Applications with
      Noise) and CLARA (Clustering Large Applications) were applied to cluster the MSI
      datasets. It is worth noting that similar patterns of spatial distribution were
      discovered through MSI data analysis using MCR-ALS, supervised ML, and
      unsupervised ML. Our protocols of data analysis can be applied to process the
      data acquired using many other types of MSI techniques, and to extract the
      overall features present in MSI results that are intractable using traditional
      data analysis approaches.

PMID- 30292297
TI  - Application of ensemble deep neural network to metabolomics studies.
AB  - Deep neural network (DNN) is a useful machine learning approach, although its
      applicability to metabolomics studies has rarely been explored. Here we describe
      the development of an ensemble DNN (EDNN) algorithm and its applicability to
      metabolomics studies. As a model case, the developed EDNN approach was applied to
      metabolomics data of various fish species collected from Japan coastal and
      estuarine environments for evaluation of a regression performance compared with
      conventional DNN, random forest, and support vector machine algorithms. This
      study also revealed that the metabolic profiles of fish muscles were correlated
      with fish size (growth) in a species-dependent manner. The performance of EDNN
      regression for fish size based on metabolic profiles was superior to that of DNN,
      random forest, and support vector machine algorithms. The EDNN approach,
      therefore, should be helpful for analyses of regression and concerns pertaining
      to classification in metabolomics studies.

PMID- 30292298
TI  - A quantitative metabolomics study of bacterial metabolites in different domains.
AB  - Absolute metabolite concentrations are essential information for quantitative
      metabolomics studies, as concentrations are closely related to metabolic
      reactions, enzyme kinetics and other important biological activities. A well
      performed metabolites extraction procedure, a reliable detection method, and a
      robust quantitative approach are all critical factors for obtaining absolute
      metabolite concentrations. Here, we used a HPLC-MS/MS based platform to
      successfully develop a 13C-labeled quantitative metabolomics approach, and
      applied this novel method to quantify bacterial metabolite concentrations in
      three different domains (i.e., intracellularly, extracellularly and to the whole
      culture), with high accuracy for a model Escherichia coli bacteria. The bacterial
      culture was grown in universal 13C-labeled medium and the metabolites were
      extracted by 40/40/20/methanol/ACN/H2O with 0.1% formic acid. One hundred and
      twenty-five metabolites were initially screened and one hundred and six 13C
      metabolites were confidently detected from the model bacteria grown in 13C
      labeled medium. A subset of twenty-one metabolites was subsequently quantified
      using 12C-metabolite chemical standards to assist the calculation of 13C
      metabolite concentration. This rigorous 13C-labled quantitative method was then
      applied to characterize the metabolic profile changes in three domains of E. coli
      going through antibiotic treatment. Our results demonstrated that metabolites
      from all three domains can be used to significantly differentiate the ampicillin
      treatment group and control group (without ampicillin). In conclusion, our work
      demonstrated that the quantitative metabolomics approach can be used as a
      valuable tool to study bacterial metabolism in different domains and to
      understand their response to environmental perturbations.

PMID- 30292299
TI  - Free oxysterols and bile acids including conjugates - Simultaneous quantification
      in human plasma and cerebrospinal fluid by liquid chromatography-tandem mass
      spectrometry.
AB  - A liquid chromatography-electrospray ionization-tandem mass spectrometry (LC
      ESI(+)-MS/MS) assay was developed and qualified for analyzing 35 analytes of the
      cholesterol metabolism, including free cholesterol, 17 free, non-esterified
      oxysterols and 17 free and conjugated bile acids in plasma and cerebrospinal
      fluid. As internal standards, 25 commercially available stable deuterium-labeled
      analogs of the analytes were used. Pre-analytical investigations included
      stability tests of analyte concentrations affected by different anticoagulation
      additives: lithium heparin-, citrate-, EDTA-K3-stabilized plasma and serum, and
      the stability in EDTA whole blood at RT. This LC-ESI(+)-MS/MS method was
      successfully applied for the analysis of paired serum/cerebrospinal fluid samples
      of patients with and without blood-brain barrier disturbance, as well as of 100
      plasma samples of a LIFE-Adult study sub-cohort. A fast and simple sample
      preparation including protein precipitation and on-line solid-phase extraction
      was developed. As little as 55 MUL of human plasma/serum or cerebrospinal fluid
      were needed for the analysis. It was possible to separate isomeric oxysterols and
      bile acids within 23 min using a C18 core-shell column. The assay is capable of
      quantifying in a linear range of 0.8-250 ng mL-1 for free hydroxycholesterols,
      0.2-10 ng mL-1 for dihydroxycholesterols, 0.2-500 ng mL-1 for bile acids and 16
      2000 MUg mL-1 for cholesterol with acceptable accuracy and precision. In
      cerebrospinal fluid one free oxysterols, five free and five conjugated bile acids
      could be quantified. No significant differences between patients with and without
      blood-brain barrier disturbance were obtained. In the LIFE-Adult sub-cohort two
      free oxysterols, four free and seven conjugated bile acids could be quantified in
      EDTA plasma. Men showed significantly higher concentrations of 26-OHC than women
      (p = 0.035). Furthermore, in women lower levels of cholic acid, glycocholic acid,
      glycodeoxycholic acid, chenodeoxycholic acid, glycochenodeoxycholic acid,
      glycoursodeoxycholic acid, glycolithocholic acid and higher levels of taurocholic
      acid, taurochenodeoxycholic acid, ursodeoxycholic acid/hyodeoxycholic acid were
      quantified.

PMID- 30292300
TI  - Exosomal lipids for classifying early and late stage non-small cell lung cancer.
AB  - Lung cancer is the leading cause of cancer deaths in the United States. Patients
      with early stage lung cancer have the best prognosis with surgical removal of the
      tumor, but the disease is often asymptomatic until advanced disease develops, and
      there are no effective blood-based screening methods for early detection of lung
      cancer in at-risk populations. We have explored the lipid profiles of blood
      plasma exosomes using ultra high-resolution Fourier transform mass spectrometry
      (UHR-FTMS) for early detection of the prevalent non-small cell lung cancers
      (NSCLC). Exosomes are nanovehicles released by various cells and tumor tissues to
      elicit important biofunctions such as immune modulation and tumor development.
      Plasma exosomal lipid profiles were acquired from 39 normal and 91 NSCLC subjects
      (44 early stage and 47 late stage). We have applied two multivariate statistical
      methods, Random Forest (RF) and Least Absolute Shrinkage and Selection Operator
      (LASSO) to classify the data. For the RF method, the Gini importance of the
      assigned lipids was calculated to select 16 lipids with top importance. Using the
      LASSO method, 7 features were selected based on a grouped LASSO penalty. The Area
      Under the Receiver Operating Characteristic curve for early and late stage cancer
      versus normal subjects using the selected lipid features was 0.85 and 0.88 for RF
      and 0.79 and 0.77 for LASSO, respectively. These results show the value of RF and
      LASSO for metabolomics data-based biomarker development, which provide robust an
      independent classifiers with sparse data sets. Application of LASSO and Random
      Forests identifies lipid features that successfully distinguish early stage lung
      cancer patient from healthy individuals.

PMID- 30292301
TI  - Utilizing ion mobility spectrometry and mass spectrometry for the analysis of
      polycyclic aromatic hydrocarbons, polychlorinated biphenyls, polybrominated
      diphenyl ethers and their metabolites.
AB  - Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and
      polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants
      originating from incomplete combustion of organic materials and synthetic
      sources. PAHs, PCBs, and PBDEs have all been shown to have a significant effect
      on human health with correlations to cancer and other diseases. Therefore,
      measuring the presence of these xenobiotics in the environment and human body is
      imperative for assessing their health risks. To date, their analyses require both
      gas chromatography and liquid chromatography separations in conjunction with mass
      spectrometry measurements for detection of both the parent molecules and their
      hydroxylated metabolites, making their studies extremely time consuming. In this
      work, we characterized PAHs, PCBs, PBDEs and their hydroxylated metabolites using
      ion mobility spectrometry coupled with mass spectrometry (IMS-MS) and in
      combination with different ionization methods including electrospray ionization
      (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure
      photoionization (APPI). The collision cross section and m/z trend lines derived
      from the IMS-MS analyses displayed distinct trends for each molecule type.
      Additionally, the rapid isomeric and molecular separations possible with IMS-MS
      showed great promise for quickly distinguishing the parent and metabolized PAH,
      PCB, and PDBE molecules in complex environmental and biological samples.

PMID- 30292302
TI  - Ratiometric quantitation of thiol metabolites using non-isotopic mass tags.
AB  - Ratiometric quantitation is used in mass spectrometry to account for variations
      in ionization efficiencies due to heterogenous sample matrixes. Isotopes are most
      commonly used to achieve ratiometric quantitation because of their ability to co
      elute chromatographically with each other and to have similar ionization
      efficiencies. In the work presented here, a new non-isotopic quantitative tagging
      approach is presented which allows chromatographic co-elution and similar
      ionization efficiencies. Using two variations of maleimide tags, t-butyl and
      cyclohexyl maleimide, thiols are quantified with a high degree of linearity up to
      five-fold concentration differences. Because these two tags have similar
      hydrophobcities, they elute simultaneously which allows them to be used for
      ratiometric quantitation. Beyond the five-fold linear range, signal compression
      is observed. This technique was able to quantify thiol changes in both in vitro
      pharmacological treatments as well as in vivo diabetic tissue.

PMID- 30292303
TI  - Recent advances in the applications of metabolomics in eye research.
AB  - Metabolomics, the identification and quantitation of metabolites in a system,
      have been applied to identify new biomarkers or elucidate disease mechanism. In
      this review, we discussed the application of metabolomics in several ocular
      diseases and recent developments in metabolomics regarding tear fluids analysis,
      data acquisition and processing.

PMID- 30292304
TI  - Supported liquid extraction coupled to gas chromatography-selective mass
      spectrometric scan modes for serum steroid profiling.
AB  - Although, steroid profiling is being applied in clinical and biochemical studies,
      improvement of the technique is still needed for accurate quantification of
      steroids in case of limited biological sample volumes. To improve analytical
      sensitivity and selectivity in comparison to that of conventional methods, a
      method that comprises supported liquid extraction (SLE) and gas chromatography
      mass spectrometry with a combination of selected-reaction and selected-ion
      monitoring modes (GC-SRM/SIM-MS) was developed. Here, this combination of SLE
      purification with GC-MS method was optimized with 37 different types of steroids
      and the results were compared to a solid-phase extraction (SPE) method. The
      devised assay led to an increase in extraction efficiency with the good
      chromatographic selectivity through a single extraction step. The limits of
      quantification of the serum steroids, ranged from 0.2 to 5 ng mL-1, except for
      cholesterol (0.2 MUg mL-1), and the correlation coefficients for calibration
      curves were higher than 0.99. The precision and accuracy were 1.4%-10.5% and
      82.7%-115.3%, respectively. The overall recoveries of 30 steroids ranged from
      62.1% to 104.3%, while that of 7 sterols was 44.7%-75.7%. Then, this validated
      method was applied to monitor the serum steroid levels of mice, which showed
      significant sex and age dependent metabolic patterns. This technique can be used
      to evaluate the metabolic changes occurring in animal models as well as in
      clinical patients.

PMID- 30292305
TI  - Serum or plasma, what is the difference? Investigations to facilitate the sample
      material selection decision making process for metabolomics studies and beyond.
AB  - In analytical chemistry serum as well as plasma are recommended as sample
      material of choice. However, blood processing for the generation of serum or
      plasma is rather different. Whether plasma or serum is the preferable sample
      material is still controversial discussed. We performed in paired samples three
      UHPLC-mass spectrometry-driven metabolomics studies. In study 1 metabolite
      profiles of serum vs plasma were compared. 46% out of 216 identified metabolites
      showed significant different levels (paired Wilcoxon signed-rank test, p < 0.05,
      FDR <0.01) with only three metabolites (methionine, C2:0- and C3:0-carnitine)
      showing lower levels in serum. In study 2 comparison of three different serum
      blood collection tubes revealed that coagulation and associated processes
      distinctly alter metabolite levels depending on the tube-specific clotting
      process. Most pronounced differences were found for the dipeptide phenylalanine
      phenylalanine (highest levels in silicate containing serum blood collection
      tubes). In study 3 possible adverse effects of platelets, which still remain in
      standard plasma even after correct processing, were investigated. No differences
      in a pattern of 216 metabolites were detected in the comparison of standard and
      platelet-free plasma (PFP). Our results give novel insights in fundamental
      differences between serum and plasma, thereby providing valuable information for
      analytical chemists for decision making to either use serum or plasma before
      starting complex and time-consuming analytical investigations.

PMID- 30292306
TI  - Recent advances in using mass spectrometry for mitochondrial metabolomics and
      lipidomics - A review.
AB  - Metabolomics and lipidomics generally targets a huge number of intermediate and
      end products of cellular metabolism in body fluids, tissues, and cells etc. At
      present, mass spectrometry (MS) based metabolic or lipid profiling of routine
      biological specimens including the whole cells, tissues, plasma, serum and urine
      etc., can cover hundreds of metabolites or lipid species in one analysis, which
      has qualified deep elucidation of global metabolic and lipid networks.
      Mitochondria are important intracellular organelles and many critical biochemical
      reactions occur here, they provide building block for new cells, control redox
      balance, participate in apoptosis and behave as a signalling platform. Evidence
      suggests high prevalence of mitochondrial dysfunction occurs in a variety of
      cancers and other diseases, thus there is an urgent demand for investigating and
      clarifying mitochondrial metabolic and lipid alterations induced by diseases.
      Nevertheless, mitochondria contribute a small fraction to cellular contents,
      profiling of whole cell is probably unsuitable for monitoring alterations in
      mitochondria. Therefore, metabolomics and lipidomics analyses specially for
      mitochondria are necessary to understand disturbed metabolic and lipid pathways
      induced by environment and diseases. However, methods for comprehensively
      profiling metabolites and lipids in mitochondria have been limited at present.
      This review summarizes the current states and progress of MS-based mitochondrial
      metabolomics and lipidomics study. Details of mitochondrial isolation procedure,
      analytical methods and their applications are described. The challenges and
      opportunities are also given.

PMID- 30292307
TI  - Comparison of modified Matyash method to conventional solvent systems for polar
      metabolite and lipid extractions.
AB  - In the last decade, metabolomics has experienced significant advances in the
      throughput and robustness of analytical methodologies. Yet the preparation of
      biofluids and low-mass tissue samples remains a laborious and potentially
      inconsistent manual process, and a significant bottleneck for high-throughput
      metabolomics. To address this, we have compared three different sample extraction
      solvent systems in three diverse sample types with the purpose of selecting an
      optimum protocol for subsequent automation of sample preparation. We have
      investigated and re-optimised the solvent ratios in the recently introduced
      methyl tert-butyl ether (MTBE)/methanol/water solvent system (here termed
      modified Matyash; 2.6/2.0/2.4, v/v/v) and compared it to the original Matyash
      method (10/3/2.5, v/v/v) and the conventional chloroform/methanol/water (stepwise
      Bligh and Dyer, 2.0/2.0/1.8, v/v/v) using two biofluids (human serum and urine)
      and one tissue (whole Daphnia magna). This is the first report of the use of the
      Matyash method for extracting metabolites from the US National Institutes of
      Health (NIH) model organism D. magna. Extracted samples were analysed by non
      targeted direct infusion mass spectrometry metabolomics or LC-MS metabolomics.
      Overall, the modified Matyash method yielded a higher number of peaks and
      putatively annotated metabolites compared to the original Matyash method (1-29%
      more peaks and 1-30% more metabolites) and the Bligh and Dyer method (4-20% more
      peaks and 1-41% more metabolites). Additionally the modified Matyash method was
      superior when considering metabolite intensities. The reproducibility of the
      modified Matyash method was higher than other methods (in 10 out of 12 datasets,
      compared to the original Matyash method; and in 8 out of 12 datasets, compared to
      the Bligh and Dyer method), based upon the observation of a lower mRSD of peak
      intensities. In conclusion, the modified Matyash method tended to provide a
      higher yield and reproducibility for most sample types in this study compared to
      two widely used methods.

PMID- 30292308
TI  - MetExpert: An expert system to enhance gas chromatography-mass spectrometry-based
      metabolite identifications.
AB  - Gas chromatography-mass spectrometry (GCMS) is an important analytical technique
      in metabolomics studies and has been routinely used for metabolite profiling of
      biological samples. Spectral matching to databases of authentic compounds are the
      preferred tools for metabolite identifications; however, the metabolic coverage
      of these databases is still limited compared to the number of known metabolites.
      Several computational tools have been developed to facilitate the interpretation
      of MS data but unfortunately most of them have limited applicability to GCMS
      based metabolite identification. In this paper, we introduce a computer-aided,
      metabolite expert system called MetExpert which emulates the metabolite
      identification ability of a human expert using orthogonal datasets including
      molecular formulas, retention indices, and EI-MS spectra to characterize the
      molecular structures. This system integrates four modules including in silico
      derivatization, metabolite-likeness evaluation, retention prediction, and
      substructure prediction. In silico derivatization increases the searchable
      chemical space for TMS-derivatized metabolites many of which are absent in
      molecular structure databases. Metabolite-likeness evaluations are an efficient
      approach to select metabolite-like molecules when querying large databases such
      as PubChem. An artificial neutral network then establishes the quantitative
      structure-retention relationships for the accurate prediction of RIs that further
      refines the candidate molecules. In addition, PLS-DA models establish
      quantitative structure-spectra relationships for the prediction of metabolite
      substructures. Finally, weighted scoring of three orthogonal evaluations
      increases the identification rates. MetExpert outperformed current state-of-the
      art methods such as MetFrag and CFM-ID for ranking the correct identifications.
      While spectral comparisons with chemical standards or de novo structural
      elucidations are necessary to validate the predictions, MetExpert provides an
      efficient and effective approach to prioritize the candidates.

PMID- 30292309
TI  - A global HILIC-MS approach to measure polar human cerebrospinal fluid metabolome:
      Exploring gender-associated variation in a cohort of elderly cognitively healthy
      subjects.
AB  - Cerebrospinal fluid (CSF) is a key body fluid that maintains the homeostasis in
      central nervous system (CNS). As a biofluid whose content reflects the brain
      metabolic activity, the CSF has been profiled in the context of neurological
      diseases to provide novel insights into the disease mechanisms. However, a global
      high-throughput approach to measure a broad diversity of polar metabolites
      present in CSF is lacking. Although still perceived as challenging and less
      reproducible, hydrophilic interaction liquid chromatography (HILIC) has recently
      evolved to offer the unprecedented coverage capacity of water-soluble metabolome.
      Here, we present a global HILIC high-resolution mass spectrometry-based (HRMS)
      approach that combines the profiling in acidic pH ESI (+) and basic pH ESI (-)
      mode to extend the coverage of CSF polar metabolome. This approach allowed us to
      annotate and measure a broad range of central carbon metabolites (implicated in
      glycolysis, TCA cycle, nucleotide, amino acid and fatty acid metabolism) in CSF
      collected from cognitively healthy elderly volunteers (n = 32), using a single
      extraction method. Metabolite annotation was achieved using the accurate mass, RT
      and MS/MS criteria, allowing for the characterization of 146 measurable
      metabolites. Exploration of characterized individual CSF profiles allowed for a
      discovery of intriguing gender-associated differences, with significantly higher
      acylcarnitine levels in men and higher taurine levels women. With this case
      study, we demonstrate the value of combined HILIC ESI +/- HRMS profiling to
      assess CSF metabolome in clinical research studies.

PMID- 30292310
TI  - The influence of culture media upon observed cell secretome metabolite profiles:
      The balance between cell viability and data interpretability.
AB  - The application of metabolomics to investigating the cell secretome has garnered
      popularity owing to the method's large-scale data output, biochemical insight,
      and prospects for novel target compound discovery. However, there are no
      standardized protocols for the use of cell growth media, a factor that can exert
      profound effects upon the detected metabolites, and thus in the interpretability
      of the resulting data. Herein, we applied a liquid chromatography-high resolution
      mass spectrometry-based metabolomics approach to examine the influence of 5
      different media combinations upon the obtained secretome of two phenotypically
      different cell lines: human embryonic kidney cells (HEK293) and L6 rat muscle
      cells. These media combinations were, M1: Medium 199, M2: Medium 199 + 2% fetal
      bovine serum (FBS), M3: Dulbecco's Modified Eagle's Medium (DMEM), M4: DMEM + 2%
      FBS and M5: Krebs-Henseleit Modified Buffer (KHB). The effect of incubation (37 
      degrees C) vs. refrigeration (4  degrees C) on DMEM medium over a 24 h period was
      also investigated. Results were validated for a selected panel of 5 metabolites
      measured from an additional cell culture experiment. Metabolomics identified a
      total of 53 polar metabolites that exhibited differential patterns on a cell type
      and medium-specific basis. We observed that choice of media was the primary
      contributor to the secreted metabolite profile detected. The addition of FBS
      resulted in unique detected metabolites, compared to media-only controls (M199
      and DMEM alone). Glutamine and pyroglutamate were more abundant in incubated
      relative to refrigerated DMEM medium. The overall metabolic pattern of the
      metabolites from the targeted approach matched with that exhibited across M1-M5
      of the metabolomics experiment, and aided in further identifying the presence of
      compounds that were below the limit of detection in metabolomics. Based upon
      these findings, we highlight the following considerations in designing a cell
      secretome-based metabolite profiling experiment: (1) multiple media combinations
      (with and without FBS) should be tested for each cell line to be investigated;
      (2) cell-free media combinations should be plated separately, and
      incubated/treated in the same experimental conditions as the cells; and (3) a
      compromise between cell death and metabolite detection should be identified in
      order to avoid batch-specific contributions from FBS supplementation.

PMID- 30292312
TI  - Characterization and annotation of oxidized glycerophosphocholines for non
      targeted metabolomics with LC-QTOF-MS data.
AB  - The biological role of oxidized glycerophosphocholines (oxPCs) is a current topic
      of research importantly contributing to the understanding of health and disease.
      Global non-targeted metabolomics offers an interesting approach to expand current
      knowledge and link oxPCs to new biological functions. Although this strategy is
      successful, it also has some limitations which are clearly noticeable during the
      identification process. For this reason, clear rules related to the
      identification of each group of metabolites are needed. This work attempts to
      provide the reader with a guideline for the recognition and annotation of
      oxidation among phosphocholines (PCs). Using several chromatographic
      characteristics and spectral information from tandem mass spectrometry, rapid and
      reliable annotation of long and short chain oxPCs can be performed. Some of this
      knowledge has been implemented in the publicly available annotation tool 'CEU
      Mass Mediator' (CMM) for semi-automated assignment of oxidation. Additionally,
      this tool was supplemented with accurate monoisotopic masses of oxPCs, expanding
      current information in other databases. Moreover, the characterization of
      oxidization products of PC(16:0/20:4) known as PAPC has been performed, providing
      a list of accurate mass product ions and neutral losses.

PMID- 30292311
TI  - Optimization of Folch, Bligh-Dyer, and Matyash sample-to-extraction solvent
      ratios for human plasma-based lipidomics studies.
AB  - In order to profile the lipidome for untargeted lipidomics applications, analysis
      by ultra-high performance liquid chromatography - high resolution mass
      spectrometry (UHPLC-HRMS) typically requires the extraction of lipid content from
      sample matrices using matrix-specific conditions. The Folch, Bligh-Dyer, and
      Matyash extraction methods, while promising approaches, were originally tailored
      to specific matrices (brain tissue, fish muscle, and E. coli, respectively). Each
      of these methods have specific solvent ratios that must be adhered to achieve
      optimal extraction. Thus, the sample-to-solvent ratios for these methods should
      be optimized for the sample matrix of interest prior to employment. This study
      evaluated the appropriate sample-to-extraction solvent ratios for human plasma
      based lipidomics studies. An advantage of employing biphasic lipid extractions is
      the ability to investigate both the aqueous and organic layers for increased
      analyte coverage in untargeted studies. Therefore, this work also evaluated the
      multi-omic capability of each lipid extraction method for plasma in an effort to
      provide a workflow capable of increasing analyte coverage in a single extraction,
      thus providing a more complete understanding of complex biological systems. In
      plasma, a decrease in sample-to-solvent ratios from 1:4, 1:10, 1:20, to 1:100
      (v/v) resulted in a gradual increase in the peak area of a diverse range of
      metabolite (aqueous layer) and lipid (organic layer) species for each extraction
      method up to the 1:20(v/v) sample-to-solvent ratio. The Bligh-Dyer and Folch
      methods yielded the highest peak areas at every plasma sample-to-solvent ratios
      for both metabolite and lipid species. Depending on the lipid class of interest,
      the Folch or Bligh-Dyer method is best suited for analysis of human plasma at a
      1:20 (v/v) sample to total solvent ratio.

PMID- 30292313
TI  - Development of simultaneous targeted metabolite quantification and untargeted
      metabolomics strategy using dual-column liquid chromatography coupled with tandem
      mass spectrometry.
AB  - Targeted quantification and untargeted global profiling are the two mainstream
      approaches, a merging of which could provide enhanced analytical potential in
      metabolomics research. Here, a simultaneous targeted quantification and
      untargeted metabolomics (STQUM) strategy was developed for more efficient,
      accurate and comprehensive metabolomics research by using ultra-high-performance
      liquid chromatography coupled with high-resolution tandem mass spectrometry (UPLC
      HRMS/MS). First, we selected 110 cancer-related metabolites as targets and
      established a dual LC sequential separation method for simultaneous analysis of
      strong and weak polar metabolites. In order to achieve efficient acquisition for
      synchronous qualitative and quantitative analysis, high-resolution, data
      dependent parallel reaction monitoring (PRM) method and data-independent all ion
      fragmentation (AIF) method were established. Their performance in targeted
      confirmation and quantification, and untargeted analysis were systematically
      investigated and assessed. In total, 78 metabolites were confidently confirmed in
      positive ion mode in both PRM and AIF assays, in which 73 metabolites can be
      accurately quantified. In addition, simultaneously untargeted profiling of 4651
      features of high reliability and validity were achieved. Both AIF and PRM methods
      revealed high confidence, sensitivity and accuracy. In the STQUM approach,
      another 15 metabolites could be accurately quantified in negative ion mode. The
      method offers a new perspective for merging the hypothesis-based targeted
      quantitative validation and untargeted biomarkers discovery in one run for
      improved analysis efficiency and integrity.

PMID- 30292314
TI  - Current and future perspectives of functional metabolomics in disease studies-A
      review.
AB  - Functional metabolomics is a new concept, which studies the functions of
      metabolites and related enzymes focused on metabolomics. It overcomes the
      shortcomings of traditional discovery metabolomics of mainly relying on
      literatures for biological interpretation. Functional metabolomics has many
      advantages. Firstly, the functional roles of metabolites and related metabolic
      enzymes are focused. Secondly, the in vivo and in vitro experiments are conducted
      to validate the metabolomics findings, therefore, increasing the reliability of
      metabolomics study and producing the new knowledge. Thirdly, functional
      metabolomics can be used by biologists to investigate functions of metabolites,
      and related genes and proteins. In this review, we summarize the analytical,
      biological and clinical platforms used in functional metabolomics studies. Recent
      progresses of functional metabolomics in cancer, metabolic diseases and
      biological phenotyping are reviewed, and future development is also predicted.
      Because of the tremendous advantages of functional metabolomics, it will have a
      bright future.

PMID- 30292315
TI  - Profiling of potential brassinosteroids in different tissues of rape flower by
      stable isotope labeling - liquid chromatography/mass spectrometry analysis.
AB  - Brassinosteroids (BRs) play crucial roles in a variety of physiological processes
      in plants. The full elucidation of the functions of RBs relies on sensitive
      detection and accurate measurement of BRs in plants. However, the identification
      and quantification of BRs are challenging due to their low abundance as well as
      poor ionization efficiencies during mass spectrometry-based analysis. Herein, we
      developed a highly sensitive and selective strategy for profiling potential BRs
      in plants by stable isotope labeling liquid chromatography multiple reaction
      monitoring scan mass spectrometry (SIL-LC-MRM-MS) analysis. In the strategy, we
      used a pair of stable isotope labeling reagents 4-phenylaminomethyl
      benzeneboronic acid (4-PAMBA) and d5-4-phenylaminomethyl-benzeneboronic acid (4
      PAMBA-d5) that can react with C22-C23 cis-diol on BRs for profiling potential BRs
      in plant tissues. The 4-PAMBA and 4-PAMBA-d5 labeled BRs could generate two
      characteristic neutral loss under collision induced dissociation (CID),
      respectively, which is used to establish the MRM-based detection and screening.
      The precursor ions of BRs labeled with 4-PAMBA and 4-PAMBA-d5 were set according
      to the reported structures of BRs, and the corresponding product ions were
      predicted by subtracting the lost neutral loss. In this respect, corresponding
      precursor ions and product ions in MRM transitions are formed. The peak pairs
      with a fixed mass difference, similar retention times and intensities were
      assigned as potential BRs. Using the developed SIL-LC-MRM-MS strategy, we
      successfully found 13 potential BR in different tissues of rape flower. Taken
      together, the SIL-LC-MRM-MS analytical strategy is promising for profiling
      potential BRs as well as other compounds that have the same functional moiety
      from complex biological samples.

PMID- 30292316
TI  - Development of an LC-ESI(-)-MS/MS method for the simultaneous quantification of
      35 isoprostanes and isofurans derived from the major n3- and n6-PUFAs.
AB  - Misregulation of oxidative and antioxidative processes in the organism -
      oxidative stress - contributes to the pathogenesis of different diseases, e.g.
      inflammatory or neurodegenerative diseases. Oxidative stress leads to
      autoxidation of polyunsaturated fatty acids giving rise to prostaglandin-like
      isoprostanes (IsoP) and isofurans (IsoF). On the one hand they could serve as
      biomarker of oxidative stress and on the other hand may act as lipid mediators,
      similarly as the enzymatically formed oxylipins. In the present paper we describe
      the development of an LC-ESI(-)-MS/MS method allowing the parallel quantification
      of 27 IsoP and 8 IsoF derived from 6 different PUFA (ALA, ARA, EPA, AdA, n6-DPA,
      DHA) within 12 min. The chromatographic separation was carried out on an RP-C18
      column (2.1 * 150 mm, 1.8 MUm) yielding narrow peaks with an average width at
      half maximum of 3.3-4.2 s. Detection was carried out on a triple quadrupole mass
      spectrometer operating in selected reaction monitoring mode allowing the
      selective detection of regioisomers. The limit of detection ranged between 0.1
      and 1 nM allowing in combination with solid phase extraction the detection of
      IsoP and IsoF at subnanomolar concentrations in biological samples. The method
      was validated for human plasma showing high accuracy and precision. Application
      of the approach on the investigation of oxidative stress in cultured cells
      indicated a distinct pattern of IsoP and IsoF in response to reactive oxygen
      species which warrants further investigation. The described method is not only
      the most comprehensive approach for the simultaneous quantification of IsoP and
      IsoF, but it was also integrated in a targeted metabolomics method (Ostermann et
      al. (2015) Anal Bioanal Chem) allowing the quantification of in total 164
      oxylipins formed enzymatically and non-enzymatically within 30.5 min.

PMID- 30292317
TI  - Lipid metabolism in mouse embryonic fibroblast cells in response to autophagy
      induced by nutrient stress.
AB  - Autophagy is of great significance in maintaining cellular homeostasis. Aberrant
      autophagy has been reported to contribute to the disease aetiology of metabolic
      syndrome, especially several key lysosomal storage disorders. However, the
      molecular mechanisms and the correlation between autophagy and lipid metabolism
      remains unclear. This study was designed and aimed to reveal the alteration of
      lipid metabolism in response to the autophagy induced by nutrient stress to give
      new insights into the molecular mechanisms between autophagy and lipid
      metabolism. An online normal-phase/reversed-phase two-dimensional liquid
      chromatography-mass spectrometry (NP/RP 2D LC-MS) method was developed to perform
      the lipidomics analysis of Atg7-/- mouse embryonic fibroblast cells (MEFs) and
      wild-type MEFs under nutrient stress. 48 and 35 lipid species in wild-type and
      Atg7-/- MEFs respectively finally meet the screening criteria with p-value less
      than 0.05 and fold change more than 1.5 in response to nutrient stress. Their
      alterations indicated that autophagy participated lipid metabolism to generate
      energy and form autophagosomes with significantly increased free fatty acids and
      glycerophospholipids, which protected wild-type MEFs from serious damages and
      delayed cell death. However, in Atg7-/- MEFs, due to the inhibition of autophagy,
      lipids were continuously consumed and cells suffered from damages even death.
      These results illustrated the close relationship between autophagy and lipid
      metabolism comprehensively and revealed diverse lipid targets for the
      investigation of autophagy.

PMID- 30292320
TI  - Editorial.

PMID- 30292318
TI  - Lipidomics reveals a systemic energy deficient state that precedes neurotoxicity
      in neonatal monkeys after sevoflurane exposure.
AB  - Although numerous studies have raised public concerns regarding the safety of
      anesthetics including sevoflurane in children, the biochemical mechanisms leading
      to anesthetics-induced neurotoxicity remain elusive. Moreover, potential
      biomarker(s) for early detection of general anesthetics-induced brain injury are
      urgent for public health. We employed an enabling technology of shotgun
      lipidomics and analyzed nearly 20 classes and subclasses of lipids present in the
      blood serum of postnatal day (PND) 5 or 6 rhesus monkeys temporally collected
      after exposure to sevoflurane at a clinically relevant concentration or room-air
      as control. Lipidomics analysis revealed numerous significant anesthetic-induced
      changes of serum lipids and their metabolites as well as short chain
      acylcarnitines in the brain and cerebrospinal fluid after anesthetic exposure.
      These include decreased carnitine and acylcarnitines, unchanged triacylglycerol
      mass but accumulation of 16:0 and 18:1 fatty acyl chains in the triacylglycerol
      pool, losses of polyunsaturated fatty acids in both non-esterified fatty acid and
      phospholipid pools, and increased 4-hydroxynonenal content as early as 2 h after
      sevoflurane exposure. Importantly, the amounts of short chain acylcarnitines in
      the brain and cerebrospinal fluid were also significantly reduced after
      anesthetic exposure. We propose that this serum lipidomic profile can serve as
      indicative of neuronal damage. Our results reveal that sevoflurane exposure
      induces an energy deficient state in the brain evidenced by reduced free and acyl
      carnitine contents, as well as the presence of a pro-inflammatory state in the
      exposed animals, providing deep insights into the underlying mechanisms
      responsible for anesthetic-induced neurotoxicity.

PMID- 30292319
TI  - Development of a simple and efficient method of harvesting and lysing adherent
      mammalian cells for chemical isotope labeling LC-MS-based cellular metabolomics.
AB  - Chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS)
      has a potential to become a very powerful platform for comprehensive and
      quantitative analysis of metabolites in cellular metabolomics. While CIL LC-MS
      with rationally designed reagents for labeling can provide much enhanced
      detection and quantification of metabolites, pre-analytical process such as cell
      harvest and cell lysis is also a critical step in the overall workflow for
      metabolomic analysis. In this study, we examined various combinations of cell
      harvest and cell lysis methods in order to develop a simple and efficient method
      for harvesting and lysing adherent mammalian cells tailored to CIL LC-MS-based
      cellular metabolomics. We evaluated and compared two cell harvest methods
      (physical scraping and trypsinization) and two cell lysis methods (glass-bead
      assisted lysis and freeze-thaw-cycle lysis). We used two types of commonly used
      mammalian cells, HeLa and MCF-7 cells, to cross-validate the findings. LC-UV
      quantification of the labeled metabolites after dansylation of cell extracts was
      used to compare the overall cell harvest and cell lysis efficiencies among
      different combination methods. It was found that scraping combined with freeze
      thaw-cycle lysis gave the highest total metabolite concentration. We also
      performed multivariate and univariate analyses of the amine/phenol submetabolome
      data generated from different preparations to investigate the impact of cell
      harvest and lysis methods on cellular metabolome profiles. Comparing to scraping,
      trypsinization caused more significant metabolome changes likely due to
      metabolite leakage and metabolite level changes. The cellular metabolomes
      obtained from the two lysis methods were found to be similar; however, freeze
      thaw-cycle lysis gave a higher lysis efficacy, compared to the glass bead method.
      We concluded that the combination of scraping and freeze-thaw-cycle was optimal
      for harvesting and lysing adherent mammalian cells for CIL LC-MS metabolomics.

PMID- 30292321
TI  - Histological investigations on the dura mater vascular system of mice.
AB  - The human dura mater encephali is a well innervated and vascularized membrane.
      Its vascular system plays a crucial role in disorders and pathological cases like
      dural hematoma, meningitis, and different headache types. To investigate these
      diseases mouse models are increasingly being used. However, the literature on the
      vascular system of the mouse dura mater is sparse and explicit studies concerned
      exclusively with its vasculature are lacking. Here we present a detailed light
      and scanning electron microscopic investigation of the supratentorial dura mater
      of the mouse species, with a focus on the largest part of it, the parietal dura
      mater. By utilizing different immunohistochemical and classical staining methods,
      a "cartography" of the vascular system was achieved. Additionally, the different
      blood vessel types with their mural cells were characterized. In contrast to
      humans, no arteries were found in the mouse parietal dura mater. Its supply is
      assured through frontolateral and occipital localized arteriolar branches. These
      arteriolar vessels exhibit in some specimens arteriolar anastomoses with one
      another. The venous blood is drained to the superior sagittal and transverse
      sinus through satellite venules accompanying the arterioles or through solitary
      venules. In all samples, large ruptured venules were identified in the
      frontolateral dural area. Scanning electron microscopy revealed that these
      vessels were ruptured on the dorsal side (skull bones-oriented side) of the dura.
      Our results contribute to the anatomical data on the mouse species and may set up
      a basis for fundamental investigation of disorders, for which the role of dural
      blood vessels is not yet clarified.

PMID- 30292322
TI  - It's been a hard day's night...But it was worth every minute.

PMID- 30292323
TI  - Relationship of the Rapid Shallow Breathing Index (RSBI) and capnography
      successfully at weaning.

PMID- 30292324
TI  - Poland syndrome and pneumothorax: the compelling evidence of an association.

PMID- 30292325
TI  - Late biliobronchial fistula.

PMID- 30292326
TI  - Prevalence and in vitro antifungal susceptibility of cryptic species of the genus
      Aspergillus isolated in clinical samples.
AB  - INTRODUCTION: The genus Aspergillus contains more than 300 species, which are
      divided into closely related groups called sections. Molecular studies have
      revealed numerous cryptic species within different sections of this genus, which
      have different profiles of antifungal susceptibility and lack diagnostic
      morphological features. However, there are few studies on the prevalence and in
      vitro antifungal susceptibility of the cryptic species of this genus. The aim of
      this study was to investigate the distribution of Aspergillus spp. among clinical
      samples, and to study their in vitro susceptibility to different antifungal
      drugs. METHOD: Over a period of 2-years (2014-2015), a total of 379 strains of
      the genus Aspergillus were isolated. Most of the isolates were classified as
      respiratory colonizations; no cases of invasive aspergillosis were found. The
      strains were identified by MALDI-TOF mass spectrometry, and susceptibility
      testing was performed by the EUCAST reference procedure. RESULTS: Twenty species
      belonging to 8 sections were identified, being A. fumigatus the most prevalent
      (44.1%). The prevalence of cryptic species was 15.3%, with a clear predominance
      of A. tubingensis. Among the tested antifungal drugs, amphotericin B was the less
      active in vitro, followed by triazole drugs and echinocandins. The cryptic
      species had minimun inhibitory concentrations (MICs) higher than the
      corresponding type species. CONCLUSIONS: Accurate identification of the genus
      Aspergillus at the species level and in vitro antifungal susceptibility testing
      are necessary because, as it has been shown, some species of this genus may show
      resistance profiles against available antifungal drugs.

PMID- 30292327
TI  - The urban injury severity score (UISS) better predicts mortality following
      penetrating gunshot wounds (GSW).
AB  - BACKGROUND: The Injury Severity Score (ISS) and the New ISS (NISS) underscore
      injury severity after GSW. This study assesses the Urban ISS (UISS), which
      incorporates all injuries. METHODS: Complete trauma program registry (TPR) data
      and chart analyses were performed on 585 patients (pts) over 28 months. Factors
      analyzed included age, gender, ISS, NISS, UISS, time of admission, intent of
      injury, race, number GSW, weapon, and outcome. RESULTS: The 585 patients could be
      categorized within three groups. The first group included 98 pts with low ISS (1
      2), no organ injuries, and early discharge; the second group included 47 patients
      with severe shock who died during operation; the third group of 442 pts were
      admitted after operation. All injury scores correlated (p < 0.001) with assault,
      number GSW, death, and length-of-stay (LOS). Death and LOS correlated closely
      with assault and the resultant number of GSW, best seen with UISS compared to ISS
      or NISS. Race and admission time did not correlate with death or LOS.
      CONCLUSIONS: UISS correlates better than ISS and NISS in victims of inner-city
      firearm injuries.

PMID- 30292328
TI  - Stop the Bleed Training empowers learners to act to prevent unnecessary
      hemorrhagic death.
AB  - BACKGROUND: Uncontrolled bleeding is a leading cause of preventable death from
      trauma. With the rise in mass casualty events, training of laypersons can be life
      saving. "Stop the Bleed" is a campaign to teach the public techniques of bleeding
      control. We believe that training in these techniques will increase participants'
      willingness and preparedness to intervene and increase knowledge of
      trauma/hemorrhage control. METHODS: We created a "Stop the Bleed" training
      program. School nurses, medical students, researchers, and community members
      participated in the program. Pre- and post-training questionnaires assessed
      participants' willingness/preparedness to intervene in a casualty event and
      knowledge of trauma/hemorrhage control. RESULTS: There was a significant change
      in attitudes after receiving training (p < 0.05). There was also an improvement
      in knowledge regarding bleeding control techniques. CONCLUSIONS: "Stop the Bleed"
      training empowers participants with the confidence and knowledge to aid others in
      preventable hemorrhagic death.

PMID- 30292329
TI  - Devil in the Detail: Intratumour Heterogeneity and Personalised Medicine for
      Bladder Cancer.

PMID- 30292330
TI  - Meta-Analysis of the Impact of Strut Thickness on Outcomes in Patients With Drug
      Eluting Stents in a Coronary Artery.
AB  - The aim of this network meta-analysis is to assess the impact of strut thickness
      on clinical outcomes in patients who underwent percutaneous coronary
      intervention. We searched Medline/PubMed and performed a Bayesian network meta
      analysis to compare outcomes of patients who underwent percutaneous coronary
      intervention with drug-eluting stents (DES) of different strut thicknesses
      (ultrathin 60 to 80 MUm; thin 81 to 100 MUm; intermediate 101 to 120 MUm; thick
      >=120 MUm). Studies comparing DES with similar strut thickness, bare metal
      stents, and fully bioresorbable scaffolds were excluded. Odds ratios with
      credible intervals (OR [CrIs]) were generated with random-effects models to
      compare outcomes. Our primary end point was stent thrombosis (ST). We identified
      69 RCTs including 80,885 patients (ultrathin group = 10,219; thin group = 36,575;
      intermediate group = 11,399; thick group = 22,692). Mean age was 64 +/- 11 years
      and 75% were male gender. When compared with thick-strut DES, ultrathin struts
      had significant less ST and myocardial infarction (OR 0.43 [CrI 0.27 to 0.68];
      and OR 0.73 [CrI 0.62 to 0.92], respectively). Sensitivity analysis including
      only studies with permanent polymer DES gave similar results. Improvement in DES
      technology with thinner struts is associated with significant reduction in ST and
      myocardial infarction compared with thicker struts.

PMID- 30292331
TI  - Relation Between Lead Exposure and Trends in Blood Pressure in Children.
AB  - Obesity raises blood pressure (BP) in children and adults. Nevertheless, as
      obesity increased around the globe, population systolic and diastolic blood
      pressures were flat or fell. Examining children is insightful because pediatric
      trends are largely unconfounded by antihypertensive therapy. Decomposing BP into
      arterial types, large artery measures (pulse pressure) increased in concert with
      obesity while small artery measures (mean arterial pressure, [MAP]) decreased,
      suggesting small arteries are the locus of the countervailing temporal trends.
      Pediatric lead exposure decreased as pediatric obesity rose. Over the period of
      rising obesity, we examined the association between lead exposure and temporal
      trends in BP. We analyzed anthropometric, BP, and laboratory data on 8-17 year
      old children from the serial cross-sectional National Health and Nutrition
      Examination Surveys 1976 through 2008. Multivariable adjusted survey regression
      was used to examine temporal trends in blood pressure in relation to blood lead
      concentrations (N = 13,501). As obesity prevalence rose from 5.3% to 24.5%, age
      sex adjusted systolic BP was flat (-0.01 [95% confidence interval (CI) -0.06,
      0.04] mm Hg/yr, p = 0.8), diastolic BP and MAP decreased (respectively -0.28 [
      0.32, -0.24] and -0.19 [CI -0.23, -0.15], both p<0.0001) while pulse pressure
      increased (0.28 [0.23, 0.32], p<0.001). Accounting for blood lead concentration
      attenuated the decreasing MAP trend by 67%. In conclusion, the contrary trends in
      pediatric BP during the rise of pediatric obesity may be substantially
      attributable to decreasing lead exposure acting on small resistance arteries.
      These results have implications for globally observed BP trends in youth and
      adults. Environmental policy altering lead levels may have long-lasting
      cardiovascular benefits.

PMID- 30292332
TI  - Comparison of Incidence, Predictors, and Outcomes of Early Infective Endocarditis
      after Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve
      Replacement in the United States.
AB  - Infective endocarditis (IE) of prosthetic or bioprosthetic heart valves is a
      serious complication associated with significant morbidity and mortality. Data on
      the incidence, risk factors, and outcomes of IE after transcatheter aortic valve
      implantation (TAVI) in the United States are limited. We used the 2013 to 2014
      Nationwide Readmissions Databases to determine the incidence of early IE after
      TAVI and surgical aortic valve replacement (SAVR) in the US. Clinical
      characteristics, independent predictors, and outcomes of patients with IE post
      TAVI were examined. In 29,306 TAVI and 66,077 SAVR patients, the incidence rates
      of early IE were 1.7% (95% confidence interval [CI] 1.5% to 1.9%) and 2.5% (95%
      CI 2.3% to 2.9%) per person-year, respectively. In a propensity-matched cohort of
      15,138 TAVI and 15,030 SAVR patients (weighted), there were no significant
      differences in the incidence rates of IE (1.7% [95% CI 1.4% to 2.0%] vs 1.9% [95%
      CI 1.6% to 2.2%] per person-year, log-rank p = 0.29) or in the median
      (interquartile range) time to IE (91 [48 to 146] vs 92 [61 to 214] days, p =
      0.13). Staphylococcus (30.4%), Streptococcus (29.9%), and Enterococcus (20.5%)
      were the most common causative organisms of IE post-TAVI. Younger age, history of
      heart failure, need for permanent pacemaker placement, cardiac arrest, major
      bleeding, and sepsis during the index TAVI hospitalization were independently
      associated with an increased risk of IE. In-hospital mortality rate during
      readmission for IE was 15.6%. In conclusion, in a nationally representative
      cohort of TAVI patients in the US, the incidence rate of early IE was 1.7% per
      person-year. Age, co-morbid conditions, invasive procedures, and complications
      during the index hospitalization were associated with incident IE post-TAVI.

PMID- 30292333
TI  - Meta-Analysis of Carvedilol for the Prevention of Anthracycline-Induced
      Cardiotoxicity.
AB  - Anthracycline is a commonly prescribed antineoplastic agent. As a consequence of
      the growing number of cancer survivors, the incidence of anthracycline-induced
      cardiotoxicity is increasing. However, the optimal primary preventive strategy is
      lacking. Therefore, we conducted a meta-analysis of all randomized controlled
      trials to evaluate the efficacy of carvedilol for the primary prevention of
      anthracycline-induced cardiotoxicity. A comprehensive search of electronic
      databases was conducted. The primary and secondary outcomes were the occurrence
      of low left ventricular ejection fraction, and the absolute change in left
      ventricular ejection fraction (LVEF), respectively. We calculated the odds ratios
      for the primary outcome and the weighted mean differences for the secondary
      outcomes using a random-effects model. We included 8 randomized controlled trials
      (633 total patients). Our results showed significantly reduced rates of low LVEF
      favoring the carvedilol group (3.2% vs 5.8%; odds ratios: 0.42; 95% confidence
      interval: 0.18 to 0.99; p = 0.05). Furthermore, there were significantly smaller
      reductions in LVEF in carvedilol-treated patients than in placebo-treated
      patients (mean differences: 2.41%; 95% confidence interval: 0.01 to 4.81; p =
      0.05). In conclusion, prophylactic administration of carvedilol in anthracycline
      treated cancer patients may reduce the early onset of left ventricular
      dysfunction compared with placebo.

PMID- 30292334
TI  - Clinical and Economic Outcomes of Ranolazine Versus Conventional Antianginals
      Users Among Veterans With Chronic Stable Angina Pectoris.
AB  - Real-world outcomes in patients with chronic stable angina treated with
      ranolazine and other antianginal medications as second- or third-line therapy are
      limited. In a historical cohort study of veterans with chronic stable angina, we
      compared time with coronary revascularization procedures, hospitalizations, and 1
      year healthcare costs between new-users of ranolazine versus conventional
      antianginals (i.e., calcium channel blockers, beta blockers, or long-acting
      nitrates) as second- or third-line. Weighted regression models calculated
      adjusted hazard ratios (HR) at up to 8-year follow-up, and adjusted incremental
      costs in the first year. Weighted groups comprised 4,699 ranolazine users and
      31,815 conventional antianginal users. Percutaneous coronary intervention (PCI)
      occurred more often in ranolazine users compared with conventional antianginal
      users (HR 1.16; 95% confidence intervals [CI] 1.08 to 1.25, p <0.001), and
      coronary artery bypass grafting occurred less often (HR 0.82; 95% CI 0.68 to
      1.00, p <0.046). All-cause and atrial fibrillation (AF) hospitalizations were
      less common with ranolazine users compared with conventional users (all-cause: HR
      0.94; 95% CI 0.90 to 0.99, p <0.010; AF:HR 0.74; 95% CI 0.67 to 0.82, p <0.001),
      and acute coronary syndrome was more common (HR 1.13; 95% CI 1.00 to 1.27, p
      <0.042). Adjusted 1-year costs were $24,517 in ranolazine users and $24,798 in
      conventional users (difference, $-280; 95% CI $-1,742 to $1,181, p = 0.71). In
      conclusion, ranolazine users had lower rates of coronary artery bypass grafting
      and all-cause and AF hospitalizations, but higher rates of percutaneous coronary
      intervention and hospitalizations due to acute coronary syndrome compared with
      conventional antianginal users. Healthcare costs were similar between ranolazine
      and conventional antianginal users.

PMID- 30292335
TI  - Effect of Gender and Genetic Mutations on Outcomes in Patients With Hypertrophic
      Cardiomyopathy.
AB  - Gender has been proposed to impact the phenotype and prognosis of hypertrophic
      cardiomyopathy (HC). Our aims were to study gender differences in the clinical
      presentation, phenotype, genotype, and outcome of HC. This retrospective single
      center cohort study included 1,007 patients with HC (62% male, 80% genotyped)
      evaluated between 1977 and 2017. Hazard ratios (HR) were calculated using
      multivariable Cox proportional hazard regression models. At first evaluation,
      female patients presented more often with symptoms (43% vs 35%, p = 0.01), were
      older than male patients (56 +/- 16 vs 49 +/- 15 years, p <0.001), and more
      frequently had hypertension (38% vs 27%, p <0.001), left ventricular outflow
      tract obstruction (37% vs 27%, p <0.001), and impaired left ventricular systolic
      (17% vs 11%, p = 0.01) and diastolic (77% vs 62%, p <0.001) function. Overall,
      the genetic yield was similar between genders (54% vs 51%, p = 0.4); however, in
      patients >=70 years, the genetic yield was less in women (15% vs 36%, p = 0.03).
      During 6.8-year follow-up (interquartile range 3.2 to 10.9), female gender was
      not independently associated with all-cause mortality (HR 1.25 [0.91 to 1.73]),
      cardiovascular mortality (HR 1.22 [0.83 to 1.79]), heart failure-related
      mortality (HR 1.77 [0.95 to 3.27]), or sudden cardiac death (SCD) and/or aborted
      SCD (HR 0.75 [0.44 to 1.30]). Interventions and nonfatal clinical events did not
      differ between the genders. In conclusion, female patients with HC present at a
      more advanced age with a different clinical, phenotypic, and genetic status.
      There is no independent association between female gender and all-cause
      mortality, cardiovascular mortality, heart failure-related mortality, or SCD.

PMID- 30292336
TI  - Underuse of Oral Anticoagulants in Patients With Ischemic Stroke and Atrial
      Fibrillation in China.
AB  - Anticoagulant therapy is an effective stroke prevention measurement for subjects
      with atrial fibrillation (AF) who are at high risk of ischemic stroke. However,
      it is reported that oral anticoagulants (OACs) are generally underused in
      clinical practice. A better awareness of current usage of anticoagulant therapy
      would enable prevention of stroke secondary to AF. Therefore, we determined the
      nationwide prevalence of AF and the frequency of OACs use among patients with
      ischemic stroke in China. Based on the China National Stroke Screening Survey, a
      representative nationwide sample of 1,252,703 adults over 40 years old during
      2013 and 2014 was involved. Information on demographic data, diagnosis of stroke,
      behavioral risk factors, family history of stroke, related diseases, and
      medications was collected. The community-based survey data showed that 5,588
      patients (12.0%) with ischemic stroke had previous, or newly diagnosed, AF.
      Therefore, more than 2.15 million ischemic stroke patients had AF in China. Among
      ischemic stroke patients with AF, the strongest risk factor was coronary heart
      disease (odds ratio = 2.53), whereas dyslipidemia accounted for the largest
      contribution (population-attributable risk proportion = 17.33%). Of ischemic
      stroke patients with AF, only 2.2% had taken OACs; of them, 98.2% had taken
      warfarin. In conclusion, a large number of ischemic stroke patients with AF are
      significantly undertreated with OACs in China. This highlights the need for
      improvement of prevention of ischemic stroke secondary to AF.

PMID- 30292337
TI  - Contrast-Induced Nephropathy After Percutaneous Coronary Intervention for Chronic
      Total Occlusion Versus Non-Occlusive Coronary Artery Disease.
AB  - Contrast volume is associated with the incidence of contrast-induced nephropathy
      (CIN), and CIN risk could be particularly high in chronic total occlusion (CTO)
      percutaneous coronary intervention (PCI). Our aim was to evaluate the incidence
      of CIN in patients who underwent CTO versus non-CTO PCI. All PCIs performed at
      our institution from January 2012 to December 2016 were included in this study.
      CIN was defined as an increase of >=0.3 mg/dl or >=50% from baseline within 72
      hours. Multivariable logistic regression analysis was performed to identify
      independent predictors of CIN. A total of 2,580 patients were included (n = 309
      CTO PCI and n = 2271 non-CTO PCI). Estimated glomerular filtration rate was lower
      in the non-CTO group (73.9 +/- 27.3 vs 77.1 +/- 24.7 ml/min/1.73/m2, p = 0.05).
      Patients in the non-CTO PCI group presented more often with acute coronary
      syndrome (47% vs 15%, p < 0.001). Contrast volume (347 +/- 159 vs 215 +/- 107 ml,
      p < 0.001) and contrast-volume-to-creatinine-clearance ratio (4.7 +/- 2.1 vs 3.2
      +/- 1.8, p < 0.001) were higher in the CTO group. There was no difference in CIN
      rates between CTO and non-CTO groups (9.4% vs 12.1%, p = 0.17). This was
      confirmed in a sensitivity analysis including only patients who underwent PCI in
      a stable clinical setting (7.7% vs 8.5%, p = 0.66). On multivariate analysis
      hypotension during/before PCI (odds ratio [OR] 2.86), acute coronary syndrome (OR
      1.86), age (OR 1.54), female sex (OR 1.51), left ventricular ejection fraction
      (OR 0.64), diabetes mellitus (OR 1.49), and contrast volume (OR 1.17) were
      independent predictors of CIN, while CTO PCI was not. In conclusion, CTO PCI is
      associated with similar rates of CIN, compared with non-CTO PCI. These findings
      persisted on sensitivity and multivariable analyses.

PMID- 30292338
TI  - Implementation of Institutional Protocols for Patients With Acute Coronary
      Syndrome: Nonclinical Factors Also Matter.

PMID- 30292339
TI  - Meta-analysis on the Association Between Norepinephrine Transporter Gene
      rs2242446, rs5569 Polymorphisms and Risk of Major Depressive Disorder.
AB  - BACKGROUND AND AIMS: The association between norepinephrine transporter (NET)
      gene polymorphisms and the risk of major depressive disorder (MDD) has been
      investigated extensively, but with contradictory findings. MATERIALS/METHODS: To
      clarify such contradiction, a comprehensive meta-analysis was conducted by
      searching PubMed, EMBASE, Web of Science and China Knowledge Resource Integrated
      Database. Odd ratios (ORs) and 95% confidence intervals (Cis) were used to
      evaluate the strength of the association. RESULTS: Totally 23 case-control
      studies regarding rs2242446 and rs5569 polymorphisms were included. Overall
      analysis and subgroup analysis indicated no significant association between NET
      gene rs2242446 polymorphism and MDD risk. However, recessive and homozygous
      models revealed a significant association between NET rs5569 polymorphism and
      increased risk of MDD. The stratified analysis further indicated significant
      associations in Asians, hospital-based studies and studies with other genotyping
      methods. CONCLUSIONS: In conclusion, NET gene rs5569 polymorphism could increase
      the risk of MDD, especially among Asians.

PMID- 30292340
TI  - Chemiluminescence-based biosensor for monitoring astronauts' health status during
      space missions: Results from the International Space Station.
AB  - During space missions, real-time monitoring of astronauts' health status is of
      crucial importance and therefore there is a strong demand for simple analytical
      devices that astronauts can use to perform clinical chemistry analyses directly
      onboard. As part of the "IN SITU Bioanalysis" project, we designed a biosensor
      for analysing salivary levels of cortisol in astronauts, a marker of chronic
      stress. The biosensor is based on the Lateral Flow Immunoassay (LFIA) approach
      coupled with chemiluminescence (CL) detection and c o m p r i s e s a 3D-printed
      plastic cartridge containing a sealed fluidic element with the LFIA strip, in
      which the flow of sample and reagents i s activated by pressing buttons on the
      cartridge and sustained by exploiting capillary forces. For measurement, the
      photon emission i s imaged employing a CL reader based on an ultrasensitive
      cooled charge-coupled device (CCD) camera. The payload was designed to operate in
      microgravity and to withstand mechanical stress, such as take-off vibrations, and
      onboard depressurization events, while the microfluidics was developed
      considering alterations of physical phenomena occurring in microgravity, such as
      bubble formation, surface wettability and liquid evaporation. The biosensor,
      which was successfully used by the Italian astronaut Paolo Nespoli during the
      VITA mission (July-December 2017), demonstrated the feasibility of performing
      sensitive LFIA analysis of salivary cortisol down to 0.4 ng/mL directly onboard
      the International Space Station. It could be easily adapted for the analysis of
      other clinical biomarkers, thus enabling the early diagnosis of diseases and the
      timely activation of appropriate countermeasures.

PMID- 30292341
TI  - Incidental bladder hernia on bone scintigraphy.

PMID- 30292342
TI  - Invited Perspective on "The Molecular Intersection Between Senescence and Major
      Depression in the Elderly".

PMID- 30292343
TI  - A rare case of emphysematous osteomyelitis of spine in uncontrolled diabetes
      mellitus.

PMID- 30292344
TI  - [Clinical research training integrated to practice in neurosurgery and
      interventional neuroradiology].

PMID- 30292345
TI  - Anosognosia for chronic dysphagia.

PMID- 30292346
TI  - Attention and awareness: Representation of visuomotor space in split-brain
      patients.
AB  - Each cerebral hemisphere primarily controls and receives sensory input with
      regard to the contralateral hand. In the disconnected brain (split-brain), when
      the hands are uncrossed, direct visual access to each hand is available to the
      controlling (contralateral) hemisphere. However, when a hand crosses the midline,
      visual and tactile information regarding the hand are presented to different
      hemispheres. It is unknown how a contralateral hemisphere codes the position and
      orientation of a visually inaccessible hand in the disconnected brain. The
      present work addresses this issue. We ask how each hemisphere represents "its"
      hand across hand positions that span the midline in the absence of cortical input
      from the contralateral hemisphere. In other words, when a hand is placed across
      the midline and is visually inaccessible, is it represented by the controlling
      hemisphere: (1) in accordance with its new position with respect to the body
      (e.g., a left hand "becomes" a right effector when it crosses the midline), (2)
      with left/right position information unaltered (e.g., the left hand is
      represented as "left" regardless of its location), or (3) stripped of its
      location information altogether? The relationship between hand position and the
      spatial codes assigned to potential responses (an index of hand representation)
      was investigated in two split-brain patients using direct (Experiment 1) and
      orthogonal (Experiment 2) S-R compatibility paradigms. S-R compatibility effects
      in split-brain patients were consistent with those displayed by typical
      individuals. These findings suggest that position-based compatibility effects do
      not rely on cross-cortical connections. Rather, each hemisphere can accurately
      represent the full visuomotor space, a process that appears to be subserved by
      subcortical connections between the hemispheres.

PMID- 30292347
TI  - We Are All Connected: Modeling the Tumor-Immune Ecosystem.
AB  - Circulating tumor-reactive immune cells link tumor responses at anatomically
      distant locations, yet this interconnectedness is poorly understood on a macro
      level. Can we use mathematical models to better understand these complex
      relationships? Recent work provides a framework to evaluate the effects that T
      cells generated at one site may have on metastases elsewhere in the body and
      suggests that in the era of immunotherapy the concept of 'local' therapy needs to
      be refined.

PMID- 30292348
TI  - Lighting Up Cancer Dynamics.
AB  - Live-cell microscopy has revealed that signaling pathways carry elaborate time
      varying activities. Yet, the connection between these dynamics and cellular
      disease has remained elusive. Recent work leverages cellular optogenetics to
      analyze the Ras-to-Erk transfer function in cancer cells. These analyses reveal
      how changes to the filtering properties of a pathway lead to the misperception of
      extracellular events. Overall, these studies suggest that mutations do not simply
      hyperactivate pathways but rather can also change their transmission properties
      in more subtle ways.

PMID- 30292349
TI  - Mutation Signatures Depend on Epigenomic Contexts.
AB  - Mutation signatures - the patterns of acquired genetic changes in somatic genomes
      - provide critical insights into DNA repair defects and exposure to mutagenic
      processes during development, aging, and cancer progression. Efforts to decipher
      the etiology of the emerging computationally predicted mutation signatures in
      cancer genomes are currently underway. Since chromatin and epigenomic contexts
      influence DNA damage and repair pathway choices, taking both epigenomic and
      sequence contexts of the mutations into consideration is likely to benefit
      interpretation of mutation signatures.

PMID- 30292350
TI  - Are Microbial Endophytes the 'Actual' Producers of Bioactive Antitumor Agents?
AB  - For millenia, plants have been a major source of medications against human and
      animal diseases. In the case of anticancer agents, a significant number of
      current agents can trace their source back to nominally plant secondary
      metabolites, with examples being taxol, vinca alkaloids, camptothecin (CPT), and
      their modified derivatives. However, it is now becoming apparent that these and
      other plant-derived materials, plus similar agents from marine sources may well
      have a microbe in their background. In this short Opinion, evidence for such
      claims are presented for some of the agents currently in use or in preclinical
      and clinical trials against cancer.

PMID- 30292351
TI  - Synthetic Lethality and Cancer - Penetrance as the Major Barrier.
AB  - Synthetic lethality has long been proposed as an approach for targeting genetic
      defects in tumours. Despite a decade of screening efforts, relatively few robust
      synthetic lethal targets have been identified. Improved genetic perturbation
      techniques, including CRISPR/Cas9 gene editing, have resulted in renewed
      enthusiasm for searching for synthetic lethal effects in cancer. An implicit
      assumption behind this enthusiasm is that the lack of reproducibly identified
      targets can be attributed to limitations of RNAi technologies. We argue here that
      a bigger hurdle is that most synthetic lethal interactions (SLIs) are not highly
      penetrant, in other words they are not robust to the extensive molecular
      heterogeneity seen in tumours. We outline strategies for identifying and
      prioritising SLIs that are most likely to be highly penetrant.

PMID- 30292352
TI  - Trinucleotide Repeat Expansion Diseases, RNAi, and Cancer.
AB  - Many neurodegenerative diseases are caused by unstable trinucleotide repeat (TNR)
      expansions located in disease-associated genes. siRNAs based on CAG repeat
      expansions effectively kill cancer cell lines in vitro through RNAi. They also
      cause significant reduction in tumor growth in a human ovarian cancer mouse model
      with no toxicity to the treated mice. This suggests that cancer cells are
      particularly sensitive to CAG TNR-derived siRNAs, and explains a reported inverse
      correlation between the length of CAG TNRs and reduced global cancer incidences
      in some CAG TNR diseases. This review discusses both mutant proteins and mutant
      RNAs as a cause of TNR diseases, with a focus on RNAi and its role in
      contributing to disease pathology and in suppressing cancer.

PMID- 30292353
TI  - Emerging Contributions of Cancer/Testis Antigens to Neoplastic Behaviors.
AB  - Tumors of nearly every origin activate the expression of genes normally
      restricted to gametogenic cells. These genes encode proteins termed cancer/testis
      (CT) antigens, since expression outside of their naturally immune-privileged site
      can evoke an immune response. Despite extensive efforts to exploit CT antigens as
      immunotherapeutic targets, investigation of whether these proteins participate in
      tumorigenic processes has lagged. Here, we discuss emerging evidence that
      demonstrates that CT antigens can confer a selective advantage to tumor cells by
      promoting oncogenic processes or permitting evasion of tumor-suppressive
      mechanisms. These advances indicate the inherent flexibility of tumor cell
      regulatory networks to engage aberrantly expressed proteins to promote neoplastic
      behaviors, which could ultimately present novel therapeutic entry points.

PMID- 30292354
TI  - Special issue - VIII Brazilian Chemometrics Workshop.

PMID- 30292355
TI  - Optimization of sample preparation procedures for evaluation of the mineral
      composition of fish feeds using ICP-based methods.
AB  - This work describes the application of an experimental design in optimizing the
      decomposition and spectrometer operational conditions for analysis of fish feeds.
      The content of 22 elements (six macroelements, four microelements and eleven
      trace elements) in feeds for fishes (ornamental and for human consumption) was
      determined by inductively coupled plasma (ICP)-based methods. Limits of
      quantification were obtained and the values ranged between 0.02 mg kg-1 (Cd) and
      76 mg kg-1 (Al). Evaluation of the methods was achieved through analysis of
      standard reference material, Oyster Tissue (NIST 1566b) and Tea (NCS DC 73351).
      Element concentrations in feed samples for ornamental fish ranged from <0.02 mg
      kg-1 (Cd) to 2.79% (P) and for fish breeding for human consumption from <0.02 mg
      kg-1 (Cd) to 2.00% (Ca). The concentrations of the elements obtained in the
      analyzed fish feeds were within the limits established by Brazilian and American
      legislation for regulated elements.

PMID- 30292356
TI  - Screening of Mangifera indica L. functional content using PCA and neural networks
      (ANN).
AB  - A method using reversed-phase high-performance liquid chromatography with diode
      array detection (HPLC-DAD) was applied after extraction with acidified methanol,
      to determine 12 bioactive phenolic compounds in the peel and pulp of the mango
      fruit (Mangifera indica L.) cultivated in the Bahia, state of Brazil. The
      proposed methodology was previously fully validated and proven successful in the
      analysis of methanolic extracts of lyophilized samples. The limits of
      quantification ranged between 0.78 and 3.14 mg L-1 and the individual recovery
      values obtained for the spiked samples ranged from 80% to 120%. The results were
      evaluated using PCA and ANN. The results indicate that the fruits are rich in
      polyphenols, mainly: ellagic acid, gallic acid, rutin and catechin, which
      contribute to their greater use as functional foods, natural antioxidants and in
      the pharmaceutical industry, as well as other applications.

PMID- 30292357
TI  - Evaluation of olive oils from the Mediterranean region by UV-Vis spectroscopy and
      Independent Component Analysis.
AB  - Extra-virgin olive oil (EVOO) from Mediterranean were analyzed by Ultraviolet
      Visible (UV-Vis) spectroscopy and Independent Component Analysis (ICA). The use
      of ICA resolution provided information over dienes (primary oxidation compound),
      polyphenolic compounds, tocopherol, carotenoids and chlorophylls when EVOO was
      evaluated by UV-Vis spectroscopy. Based on these data, ICA could be used to
      determine the contribution of chemical compounds to the composition of EVOO
      produced in different regions from Mediterranean. The results suggest that the
      combination of UV-Vis measurements and ICA makes possible the EVOO evaluation,
      and can contribute to suggesting that a foodstuff comes from an alleged origin.
      The proposed methodology is a low cost, fast and sample preparation free
      methodology to highlights the EVOO characteristics produced in the Mediterranean
      region.

PMID- 30292358
TI  - Multivariate optimization of ultrasound-assisted extraction using Doehlert matrix
      for simultaneous determination of Fe and Ni in vegetable oils by high-resolution
      continuum source graphite furnace atomic absorption spectrometry.
AB  - A method for simultaneous determination of Fe (232.036 nm) and Ni (232.195 nm) in
      vegetable oil samples by high-resolution continuum source graphite furnace atomic
      absorption spectrometry (HR-CS GF AAS) after an acid extraction of the analytes
      is proposed. In the extraction step, hydrochloric, nitric and acetic acid
      solutions were tested. The optimization of the procedure was performed by
      applying Doehlert matrix, and multiple response was used for simultaneous
      evaluation of the performance of the extraction. The optimum conditions were:
      extraction time of 17 min, extraction temperature of 39  degrees C and sonication
      amplitude of 42%, employing 0.5 mol L-1 HCl as the extracting solvent. The limits
      of quantification were 60 and 160 ng g-1 for Fe and Ni, respectively. The method
      was applied to the analysis of vegetable oil samples and the results were
      compared with a method employing inductively coupled plasma optical emission
      spectrometry (ICP OES).

PMID- 30292359
TI  - Development of procedure for sample preparation of cashew nuts using mixture
      design and evaluation of nutrient profiles by Kohonen neural network.
AB  - A procedure using ICP OES for sample preparation for the determination of copper,
      iron and manganese in cashew nuts was developed. Constrained simplex-centroid
      design was applied in the optimization of the digestion in microwave oven
      procedure, and the results evaluated from topological maps of the Kohonen
      network. The best proportion evaluated for the digestion of the sample with HNO3,
      H2O2 and H2O was 10:45:45 (%). With optimized conditions, the detection limits
      were 0.63, 4.3 and 0.37 mg kg-1, and quantification 2.1, 14 and 1.2 mg kg-1 for
      Cu, Fe and Mg, respectively. The precision (% RSD) was 1.84, 2.31 and 2.73, for
      Cu, Fe and Mg, respectively. The procedure proposed had the accuracy confirmed
      using NIST 1568b (at 95% reliability) and was applied in the samples obtaining
      concentrations in the range of 10.7-19.4, 44.3-67.2 and 11.0-21.4 mg kg-1 for Cu,
      Fe and Mg, respectively.

PMID- 30292360
TI  - Discrimination between conventional and omega-3 fatty acids enriched eggs by FT
      Raman spectroscopy and chemometric tools.
AB  - This work developed an analytical method to differentiate conventional and omega
      3 fat acids enriched eggs by Raman spectroscopy and multivariate supervised
      classification with Partial Least Squares Discriminant Analysis (PLS-DA). Forty
      samples of enriched eggs and forty samples of different types of common eggs from
      different batches were used to build the model. Firstly, gas chromatography was
      employed to analyze fatty acid profiles in egg samples. Raman spectra of the yolk
      extracts were recorded in the range from 3100 to 990 cm-1. PLS-DA model was able
      to correctly classify samples with nearly 100% success rate. This model was
      validated estimating appropriate figures of merit. Predictions uncertainties were
      also estimated by bootstrap resampling. The most discriminant Raman modes were
      identified based on VIP (variables importance in projection) scores. This method
      has potential to assist food industries and regulatory agencies for food quality
      control, allowing detecting frauds and enabling faster and reliable analyzes.

PMID- 30292361
TI  - Multielementar/centesimal composition and determination of bioactive phenolics in
      dried fruits and capsules containing Goji berries (Lycium barbarum L.).
AB  - The elemental/centesimal composition of dried fruits and capsules containing Goji
      berries (Lycium barbarum L.) was evaluated by ICP OES after two digestion
      procedures. Furthermore, phenolic acid compounds and flavonoids were quantified
      by HPLC-UV-DAD. Precision, accuracy, LOD and LOQ were evaluated. The samples
      showed similar contents of proteins, lipids and carbohydrates. The metal contents
      in the samples were found at different levels (minimum-maximum, in mg kg-1), as
      follows: Ca (181.1-200.2); Cu (1.703-2.145); Fe (7.420-7.852); K (81.78-83.59);
      Mg (92.58-95.12); Mn (1.630-2.570); Na (587.9-590.7); P (3.124-3.360); Se (2.812
      3.345); V (0.055-0.062) and Zn (2.325-2.610). Al, As, Ba Cd, Co, Ni, P, Pb, Sb,
      Sn and Sr showed values below the LOD. Accuracy was assessed by analysis of
      tomato leaves (NIST 1573a). Eight bioactive phenolic compounds (caffeic,
      chlorogenic, ellagic, ferulic, gallic, p-coumaric, syringic and vanillic acids)
      and two flavonoids [(+)-catequin and rutin] were determined, in levels of 55.5
      83.700 and 172.3-2982.4 mg kg-1, respectively.

PMID- 30292362
TI  - Seasonal changes and solvent effects on fractionated functional food component
      yields from Mikania laevigata leaves.
AB  - Statistical mixture design extraction and fractionation of Mikania plant samples
      were carried out to quantitatively study seasonal and solvent composition effects
      as well as their interactions on secondary metabolites. The mixture design
      consisted of ethanol, acetone, dichloromethane and chloroform solvents and their
      binary, ternary and quaternary mixtures. Yields were measured for the crude
      extract and its neutral, organic, basic, polar and fiber fractions obtained with
      each solvent composition from samples harvested during 2010. Two-way ANOVA found
      statistically significant seasonal and solvent effects for the crude extract and
      all the fractions except for the polar fraction solvent. The best solvent
      extractor depends the harvest season. High crude, organic and polar fraction
      yields in the summer are correlated with the coumarin UV-vis absorbance at 274
      nm. Crude yields of mixtures containing ethanol are correlated with the coumarin
      absorbances in summer, winter and spring whereas mixtures without ethanol show no
      significant correlation.

PMID- 30292363
TI  - Microwave-assisted digestion using diluted HNO3 and H2O2 for macro and
      microelements determination in guarana samples by ICP OES.
AB  - A microwave-assisted digestion procedure using diluted HNO3 and H2O2 was
      developed for multi-element determination in guarana samples by ICP OES.
      Optimization step was performed employing a mixture design with pseudocomponents
      using HNO3, H2O2 and H2O. The analytical signal of each element, residual acidity
      and residual carbon content were optimized simultaneously using the desirability
      function. The best condition for digestion of a 250 mg sample mass resulted from
      a mixture constituted by 1.0 mL of HNO3, 3.0 mL of H2O2 and 6.0 mL of H2O. This
      condition allowed final digests with residual acidity and residual carbon content
      of 0.4 mol L-1 and 6.5%, respectively. The method was validated and applied for
      the determination of K, Ca, Mg, S, P, Cu, Fe, Mn and Zn in 72 guarana seed
      samples from Bahia state. This work presents unpublished results about the
      mineral composition of guarana seed samples produced in Bahia state, Brazil.

PMID- 30292364
TI  - Mineral and centesimal composition evaluation of conventional and organic
      cultivars sweet potato (Ipomoea batatas (L.) Lam) using chemometric tools.
AB  - Sweet potato is a food consumed in the world. In this work, the minerals and
      centesimal composition in sweet potatoes of organic and conventional cultivars
      was investigated. The accuracy was confirmed with a certified reference material
      of apple leaves (NIST 1515). The quantification of the samples was performed by
      inductively coupled plasma optical emission spectrometry and the digestion
      efficiency was evaluated by residual carbon content. The mean concentrations (in
      mg/100 g) of minerals were: 23.5 and 40.7 (Ca); 0.082 and 0.159 (Cu); 0.303 and
      0.481 (Fe); 197 and 381 (K); 166 and 35.7 (Mg); 0.183 and 1.15 (Mn); 68.6 and
      0.433 (Na); 54.1 and 62.2 (P) and 0.197 and 0.261 (Zn) for conventional and
      organic cultivars, respectively. Average centesimal concentrations in
      conventional and organic cultivars (in %), were: 72 and 72 (moisture); 0.87 and
      0.90 (ashes); 1.5 and 1.4 (proteins); 0.63 and 0.54 (lipids) and 24.8 and 23.9
      (carbohydrates).

PMID- 30292365
TI  - Mineral content in mustard leaves according to the cooking method.
AB  - This work evaluated the influence of the cooking methods (cooked in a water bath,
      in a stove, and in a microwave oven) on the mineral composition of mustard leaves
      (Sinapis alba). So, raw and cooked samples were digested and afterward the
      elements calcium, magnesium, potassium, sodium, iron, zinc, phosphor, barium and
      sulfur were determined using inductively coupled plasma optical emission
      spectrometry (ICP OES). The experimental work involved a set of five samples from
      different locations, processed in triplicates. The results were evaluated
      employing Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA)
      and Linear Discriminate Analysis (LDA). All techniques showed that the mineral
      content of the raw and cooked samples in a water bath is different from the
      samples cooked in stove and microwave oven. Especially for potassium, whose
      content is strictly controlled for chronic renal patients, this study showed that
      cooking using microwave oven has the greatest efficiency for reduction.

PMID- 30292366
TI  - Attenuated Total Reflectance Fourier Transform Spectroscopy (ATR-FTIR) and
      chemometrics for discrimination of espresso coffees with different sensory
      characteristics.
AB  - Coffee cup quality, determined by the sensory attributes evaluated by
      professional tasters, is a decisive factor for evaluating coffee, with the
      "Specialty Coffee Association of America" (SCAA) classification being nowadays
      considered the most suitable. Panels of trained coffee tasters are used by the
      industry to describe and evaluate beverage quality, but those evaluations can be
      subjective and time demanding. Recent studies have demonstrated the potential of
      spectroscopy-based methods for establishing parameters of quality in the analysis
      of food products, including coffee. Thus, the aim of this study was to evaluate
      the potential of ATR-FTIR and chemometrics to discriminate espresso coffees with
      different sensory characteristics reported by a panel of coffee tasters. The
      results showed good consistency among coffee tasters. PLS-DA models based on
      spectroscopic data were able to classify samples according to sensory attributes,
      confirming the potential of FTIR and chemometrics in coffee quality evaluation.

PMID- 30292367
TI  - Seasonal variation in the chemical composition of two chemotypes of Lippia alba.
AB  - Lippia alba is a popular Brazilian herb known as 'cidreira' that presents several
      chemotypes which exhibit different chemical profile and they are widely used as
      seasonings and traditional medicine. This work describes the seasonal variation
      of metabolites of polar extracts of carvone and linalool chemotypes, identified
      by GC-MS analyses of the essential oils. A methodology was elaborated in order to
      obtain a seasonal variation in the chemical composition of leaf employing HPLC
      DAD. Acteoside, isoacteoside, geneposidic acid, 8-epi-loganin, mussaenoside,
      luteolin 7-O-glucoside, apigenin 7-O-glucuronide and tricin 7-O-diglucuronide
      have been isolated and identified for validation procedures and chromatographic
      analysis. Geneposidic acid was presented in all samples, in contrast to the 8-epi
      loganin and, mussaenoside which were presented only in the carvone-chemotype.
      Acteoside was the major metabolite detected from July to November while tricin-7
      O-diglucuronide was the major compound in all other months. Besides,
      phenylpropanoids are predominant in winter and flavonoids in summer season.

PMID- 30292368
TI  - Determination of six veterinary pharmaceuticals in egg by liquid chromatography:
      Chemometric optimization of a novel air assisted-dispersive liquid-liquid
      microextraction by solid floating organic drop.
AB  - Two extraction strategies for albendazole, chloramphenicol, trimethoprim,
      enrofloxacin, oxitetracycline and nicarbazin in egg were optimized for its
      quantitation by liquid chromatography. First, two designs were built to find out
      the optimized condition for the air assisted-dispersive liquid-liquid
      microextraction based on solidification of organic drop: a fractional factorial
      and a central composite design. The optimum conditions were 1140uL of water,
      125mg of ZnSO4, 1175uL of acetonitrile, 1200uL of methyl alcohol and 740uL of
      propanone, using 1.00g of homogenized egg and 50uL of 1-dodecanol. Second, two
      designs were also built to optimize the dispersive liquid-liquid microextraction:
      a central composite design and a mixture design to set the combination of the re
      suspended solvents. The optimum conditions were 1840MUL of acetonitrile and
      160MUL of dichloromethane and the re-suspended mixture consisting in acetonitrile
      and sodium phosphate buffer 10mmolL-1 pH = 3.50 (30:70v/v).

PMID- 30292369
TI  - Simultaneous determination of mercury and selenium in fish by CVG AFS.
AB  - In this work, an analytical method was proposed for the simultaneous
      determination of mercury and selenium in fish samples using Atomic Fluorescence
      Spectrometry (AFS). Multivariate designs were performed to evaluate the variables
      and optimize the best condition of chemical vapor generation (CVG) and
      simultaneous determination of mercury and selenium by AFS. Fish samples were
      prepared via acid digestion in digester block with cold finger reflux system,
      which ensured that the elements were not lost by volatility. The proposed
      analytical method was validated, and excellent figures of merit have been
      achieved, such as detection limits of 0.33 and 9.18 ng g-1 for mercury and
      selenium, respectively. The method was applied for simultaneous determination of
      mercury and selenium in canned sardines. Mercury concentrations ranged from 0.057
      to 0.203 MUg g-1 and selenium concentration from 1.76 to 2.21 MUg g-1, providing
      a mean molar ratio (Se:Hg) equivalent to 36.

PMID- 30292370
TI  - Multivariate optimization techniques in food analysis - A review.
AB  - This work presents a critical review of multivariate techniques employed for
      optimization of methods developed in food analysis. A comparison between the
      response surface methodologies has been performed, it evidencing advantages and
      drawbacks of these. Applications of the main chemometric tools (central composite
      and Box Behnken designs and Doehlert matrix) often utilized for optimization of
      sample preparation procedures and also instrumental conditions of analytical
      techniques for determination of organic and inorganic species in food samples are
      shown. Also, a brief discussion on the use of multiple responses and robustness
      test in food analysis has been presented.

PMID- 30292371
TI  - A simple voltammetric electronic tongue for the analysis of coffee adulterations.
AB  - This work presents a simple and low-cost analytical approach to detect
      adulterations in ground roasted coffee by using voltammetry and chemometrics. The
      voltammogram of a coffee extract (prepared as simulating a home-made coffee cup)
      obtained with a single working electrode is submitted to pattern recognition
      analysis preceded by variable selection to detect the addition of coffee husks
      and sticks (adulterated/unadulterated), or evaluate the shelf-life condition
      (expired/unexpired). Two pattern recognition methods were tested: linear
      discriminant analysis (LDA) with variable selection by successive projections
      algorithm (SPA), or genetic algorithm (GA); and partial least squares
      discriminant analysis (PLS-DA). Both LDA models presented satisfactory results.
      The voltammograms were also evaluated for the quantitative determination of the
      percentage of impurities in ground roasted coffees. PLS and multivariate linear
      regression (MLR) preceded by variable selection with SPA or GA were evaluated. An
      excellent predictive power (RMSEP = 0.05%) was obtained with MLR aided by GA.

PMID- 30292372
TI  - Multivariate analysis of the composition of bioactive in tea of the species
      Camellia sinensis.
AB  - This study deals with the development of a separation and quantification method
      by high performance liquid chromatography with a diode array detector (HPLC-
      DAD), for the determination of phenolic acids and methylxanthines in tea
      (Camellia Sinensis) samples. Six phenolic acids (Gallic, trans-cinnamic, caffeic,
      ferulic and p-coumaric acids) and two methylxanthines (caffeine, theobromine)
      were studied, according to the principles of green chemistry, with the goal of
      comparing teas with different processing level. After development and validation
      of separation and extraction methods was applied to 11 extracts obtained by
      infusions of green and black tea samples in commercial areas of the city of
      Salvador-BA, showing feasible and efficient. Was employed multivariate data
      analysis and the Tukey test to correlate the chromatographic profile with the
      different samples. Principal component and analysis and hierarchical cluster
      analysis were used for the chromatographic analysis, allowing the visualization
      of two groups, formed by green and black tea samples.

PMID- 30292373
TI  - Inorganic and organic contaminants in drinking water stored in polyethylene
      cisterns.
AB  - This work evaluated the presence of contaminants in stored rainwater in 36
      polyethylene tanks installed in two rural communities of the semiarid of Bahia,
      Brazil. Carbonyl compounds were analyzed by High Performance Liquid
      Chromatography (HPLC-UV), BTEX (Benzene, Toluene, Ethylbenzene and Xylenes) by
      gas chromatoghaphy (GC-FID), and trace elements by inductively coupled plasma
      optical emission spectrometry (ICP-OES). Seven carbonyl compounds were quantified
      including acrolein (<3-115 ug L-1), which is considered a potent mutagenic agent,
      above the potability limit in 75% of the cases. Trace elements such as copper,
      zinc, barium, aluminum and lead, more frequently found, were also quantified, and
      lead (<0,56-99 ug L-1) was above the tolerable limit for drinking water of 10 MUg
      L-1 in 73% of the cases. The results show that the stored water in polyethylene
      cisterns in the Brazilian semiarid region does not present satisfactory
      conditions for human consumption.

PMID- 30292374
TI  - Thermal rice oil degradation evaluated by UV-Vis-NIR and PARAFAC.
AB  - Thermal rice oil degradation was evaluated by UV-Vis and NIR in three-way arrays
      assembled with samples, different temperatures, and the absorbance at different
      wavelengths by applying PARAFAC chemometric method. The loadings matrix of the
      mode corresponding to the samples (scores) contains the information related to
      the samples. The loadings on the temperature mode resemble kinetics profiles.
      These profiles change with the nature of the component responsible for the factor
      and evolve with the heating temperature. The loadings on the spectral mode reveal
      the antioxidants gamma-oryzanol and tocopherol, and oxidation products are the
      components responsible for the two factors. The results achieved showed that the
      antioxidants concentration decreases starting at 70  degrees C while oxidation
      products start to increase more pronounced after 90  degrees C. The proposed
      method is shown to be a simple and fast way to obtain information about the
      oxidative stability of rice oils.

PMID- 30292375
TI  - Determination of nutrients in sugarcane juice using slurry sampling and detection
      by ICP OES.
AB  - The fractional factorial and Doehlert designs for optimization of a slurry
      sampling procedure to determine of nutrients in sugarcane juice by inductively
      coupled plasma optical emission spectrometry (ICP OES) were applied. External
      calibration curves were used for direct analysis of the slurry. This procedure
      allowed determination of Ca, Cu, Fe, K and Mg with limits of detection (LoD)
      obtained of 2.0, 0.04, 0.2, 1.0 and 1.5 mg L-1, respectively. The precision was
      expressed as relative standard deviation (%RSD), being better than 1.4% (n = 3).
      Accuracy was confirmed by comparison with sample digestion method. The results
      for analysis of fourteen sugarcane juices samples demonstrated that the nutrients
      Ca, Cu, Fe, K and Mg have average contents of 108, 0.506, 6.40, 470 and 114 mg L
      1, respectively. The proposed analytical method is a good alternative for
      simultaneous determination of nutrients in sugarcane juice using introduction of
      slurries and detection by ICP OES.

PMID- 30292376
TI  - Multivariate data analysis of trace elements in bivalve molluscs:
      Characterization and food safety evaluation.
AB  - Four species of bivalve molluscs (Anomalocardia brasiliana, Iphigenia brasiliana,
      Lucina pectinata and Trachycardium muricatum) were collected in the Todos os
      Santos Bay (TSB), Bahia, Brazil, in order to evaluate As, Cd, Co, Cu, Cr, Fe, Mn,
      Ni, Pb, Se, V and Zn levels and, consequently, the risk of bivalve mollusc
      consumption in humans. The samples were analyzed by inductively coupled plasma
      optical emission spectrometry (ICP OES) and inductively coupled plasma mass
      spectrometry (ICP-MS) after closed-vessel microwave digestion. The accuracy was
      confirmed using the certified reference materials of oyster tissue (NIST 1566b)
      and mussel tissue (NIST 2977), and the results were statistically equivalent to
      the certified values. Application of principal component analysis (PCA) and
      hierarchical cluster analysis (HCA) showed a tendency to form two groups between
      samples of Lucina pectinata and Trachycardium muricatum. All species showed As
      and Cr concentrations higher than the maximum tolerable limit specified in
      Brazilian legislation.

PMID- 30292377
TI  - Doehlert design in the optimization of ultrasound assisted dissolution of fish
      fillet samples with tetramethyl ammonium hydroxide for metals determination using
      FAAS.
AB  - Doehlert design and desirability function were used in the optimization of an
      ultrasound assisted dissolution method of fish fillet samples with tetramethyl
      ammonium hydroxide (TMAH) for the determination of Ca, Fe, Zn and Mg by flame
      atomic absorption spectrometry. The variables values after optimization were 620
      MUL (volume of TMAH), 25 min (sonication time) and 46  degrees C (bath
      temperature). The quantification limits for Ca, Mg, Fe and Zn were 56, 107, 23
      and 2.9 MUg g-1, respectively. Accuracy was evaluated by comparing the results
      generated from the analysis of the samples treated by the proposed method and by
      wet digestion. Additionally, accuracy for Fe and Zn was assessed by the analysis
      of certified reference materials Tort-3 (Lobster hepatopancreas), ERM-CE 278
      (mussel tissue) and Dolt-4 (Fish liver). There were no significant differences
      between the results obtained at a 95% confidence level when results were
      evaluated by t-test application.

PMID- 30292378
TI  - Simultaneous identification of the wood types in aged cachacas and their
      adulterations with wood extracts using digital images and SPA-LDA.
AB  - Cachaca is a sugarcane-derived alcoholic spirit exclusively produced in Brazil.
      It can be aged in barrels made from different types of wood, similar to other
      distilled beverages. The choice of wood type promotes different effects on color,
      flavor, aroma and consequently the price of cachaca, favoring fraudulent
      activities. This paper proposes the simultaneous identification of different wood
      types in aged cachacas and their adulterations with wood extracts using a digital
      image based methodology employing color histograms obtained from digital images
      associated with pattern recognition methods, without any sample preparation step.
      Linear Discriminant Analysis, coupled with Successive Projections Algorithm for
      variable selection (SPA-LDA), obtained the best results, reaching accuracy,
      sensitivity, and specificity rates higher than 90.0% in the test set. This can be
      a rapid and reliable tool to prevent fraudulent labeling; ensuring that what is
      on the label reflects the quality of aged cachacas, affording security to
      consumers and regulatory agencies.

PMID- 30292379
TI  - Quantification of mineral composition of Brazilian bee pollen by near infrared
      spectroscopy and PLS regression.
AB  - Bee pollen consumption has increased in the last years, mainly due to its
      nutritional value and therapeutic applications. The quantification of mineral
      constituents is of great importance in order to evaluate both, the toxicity and
      the beneficial effect of essential elements. The purpose of this work was to
      quantify the essential elements, Ca, Mg, Zn, P and K, by diffuse reflectance
      spectra in the near infrared region (NIR) combined with partial least squares
      regression (PLS), which is a clean and fast method. Reference method used was ICP
      OES. The determination coefficients for calibration models (R2) were above 0.87
      and the mean percent calibration error varied from 5 to 10%. For external
      validation R2 values were higher than 0.76. The results indicated that NIR
      spectroscopy can be useful for an approximate quantification of these minerals in
      bee pollen samples and can be used as a faster alternative to the standard
      methodologies.

PMID- 30292380
TI  - Evaluation of macro and micronutrient elements content from soft drinks using
      principal component analysis and Kohonen self-organizing maps.
AB  - This study approaches the determination of nine elements from Brazilian
      carbonated soft drinks of several flavors and manufactures using inductively
      coupled plasma optical emission spectrometry (ICP OES). The concentrations of the
      elements varied as follows: (in ug L-1: Cu: 4.00-78.0; Fe: 74.0-506; Mn: 20.0
      66.0; Zn: 104-584) and (in mg L-1: Ca: 4.81-16.2; K: 6.73-260; Na: 26.0-175; S:
      1.43-5.41; P: 0.186-219). Principal component analysis has shown some tendencies
      to form two groups according to the drink flavor (orange and cola), but only cola
      presented a clear and complete separation. Using Kohonen maps, it was observed a
      tendency to form three flavor groups: (i) cola, (ii) orange and lemon, and (iii)
      guarana. However, this last tool proved to be more accurate in the groups'
      formation.

PMID- 30292381
TI  - Direct determination of Ca, K, Mg, Na, P, S, Fe and Zn in bivalve mollusks by
      wavelength dispersive X-ray fluorescence (WDXRF) and laser-induced breakdown
      spectroscopy (LIBS).
AB  - This study aims to develop methods for determination of Ca, K, Mg and Na by laser
      induced breakdown spectroscopy (LIBS) and Ca, K, Mg, Na, P, S, Fe and Zn by
      wavelength dispersive X-ray fluorescence (WDXRF) in pressed pellets bivalve
      mollusks. LIBS and WDXRF calibration models were built with references values
      determined by inductively coupled plasma optical emission spectrometry (ICP OES)
      after acid digestion. The calibration models for LIBS and WDXRF were obtained
      from 28 samples (14 for calibration and 14 for validation). It was possible to
      implement a validation between LIBS and WDXRF methods for elements Ca, K, Mg and
      Na. The proposed calibration model obtained using LIBS and WDXRF data presented a
      good correlation with reference values obtained by ICP OES.

PMID- 30292382
TI  - Mathematical modeling of multicomponent NaCl and KCl diffusion process during the
      salting of pre-cooked champignon mushrooms.
AB  - Wet salting is an old preservation method however the NaCl has been frequently
      associated to high blood pressure issues. The KCl has been used as partial
      replacement without affecting the acceptability of the final product. In this
      study, the simultaneous diffusion of NaCl and KCl in champignon mushrooms in
      static brine and brine under agitation was modeled based on the generalization of
      Fick's second diffusion law and simulated using the finite element method. Main
      and crossed diffusion coefficients, as well as the Biot number, were determined
      using the super modified simplex optimization method by means of percentage error
      minimization. Deviations between the simulated and experimental data were 5.78%
      for NaCl and 4.78% for KCl in static brine and 4.95% for NaCl and 4.35% for KCl
      in brine with agitation and, the main diffusion coefficients 2.692 * 10-10 m2s-1
      for sodium and 2.953 * 10-10 m2s-1 for potassium were obtained.

PMID- 30292383
TI  - Corrigendum to "Randomized open-labbel non-inferiority trial of acetaminophen or
      loxoprofen for patients with acute low back pain" [Journal of Orthopaedic Science
      23 (2018) 483-487].

PMID- 30292384
TI  - [Kelly-Paterson Syndrome and coeliac disease in adult].

PMID- 30292385
TI  - Characterization of virulence factors, antimicrobial resistance patterns and
      biofilm formation of Pseudomonas aeruginosa and Staphylococcus spp. strains
      isolated from corneal infection.
AB  - INTRODUCTION: Infectious keratitis is a serious ocular infection that can lead to
      severe visual impairment and blindness. Bacterial pathogens are responsible for
      nearly half of infectious keratitis cases. This study was performed to determine
      the virulence factors, antimicrobial resistance patterns, and biofilm formation
      ability of Pseudomonas aeruginosa and Staphylococcus spp. strains isolated from
      corneal infections. METHODS: A total of 56 corneal scraping samples were
      collected over 8 months. P. aeruginosa and staphylococcal strains were identified
      by phenotypic and genotypic methods. Determination of multidrug resistance was
      performed according to its definition of multidrug resistance (MDR). Detection of
      antimicrobial resistance genes and determinants of virulence were also performed
      using standard procedures. Biofilm formation ability of the isolates was
      determined by colorimetric microtitration plate assay and Modified Congo red agar
      (MCRA). RESULTS: In the present study, P. aeruginosa, MSSA, MRSA, MS-CoNS and MR
      CoNS strains were isolated from corneal infections. Multidrug resistance was
      observed in 42.9% and 57.1% of P. aeruginosa and Staphylococcus spp.,
      respectively. The most frequent virulence genes among P. aeruginosa strains were
      exoA and exoS (100%) followed by exoU (71.4%) and lasB (28.6%). All the P.
      aeruginosa isolates were biofilm producers and carried the algD gene (100%). All
      staphylococcal strains were negative for pvl gene amplification. Biofilm
      formation was also observed in 4 (57.1%) isolates. Both icaA and icaD genes were
      detected in the biofilm producers. CONCLUSION: Our results indicated that P.
      aeruginosa and Staphylococcus spp. were the most prevalent bacterial agents that
      cause corneal infections. However, their virulence traits and biofilm formation
      ability were noteworthy.

PMID- 30292386
TI  - The Value of Cerebral Oximetry Monitoring in Cardiac Surgery: Challenges and
      Solutions in Adult and Pediatric Practice.

PMID- 30292387
TI  - Preoperative Cardiac Stress Testing- A Thing of the Past?

PMID- 30292388
TI  - Three-Dimensional Assessment of the Mitral Valve: Looking Toward the Future.

PMID- 30292389
TI  - A Rare Cause of Stroke FourWeeks After Ascending Aortic Aneurysm Repair.

PMID- 30292390
TI  - Bilirubin Removal Using CytoSorb Filter in a Cardiac Surgical Patient.

PMID- 30292391
TI  - How to Measure Outcome-The Art of Evaluating Success.

PMID- 30292392
TI  - Molecular characterization of Aspergilli isolated from outdoor air.
AB  - Ubiquitous airborne conidia of the genus Aspergillus are responsible for a
      diverse group of human disorders from allergy to life treating invasive
      aspergillosis and mycotoxicoses. The aim of this study was to determine the
      population structure of Aspergillus isolated from outdoor air in Tehran by
      comparing the nucleotide sequences of ITS region and the PCR-RFLP molecular
      method. Internal transcribed spacer domains of 47 Aspergillus spp. were amplified
      and sequenced and PCR products were digested individually with restriction
      enzymes TaqI and EcoRI. For all species the PCR reaction produced a fragment of
      approximately 600bp in length. All of the nucleotide sequences were highly
      similar with the corresponding reference sequences registered at the gene bank.
      The all isolates displayed same banding pattern on the basis EcoR1 cleavage.
      While Taq1 enzyme profiling provided 5 different banding pattern. The results
      show that the A. niger section has the highest frequency with 27 isolates
      (57.4%). Of these, 23 isolates (48.9%) belonged to the A. niger complex and 4
      isolates (8.5%) to the A. aculeatus complex. The A. flavus complex was also
      placed in the next ranking with 9 isolates (19.1%). These results strongly
      support the need for using molecular markers as an auxiliary tool in
      differentiating Aspergillus species.

PMID- 30292393
TI  - Effects of Doxorubicin on the Liquid-Liquid Phase Change Properties of Elastin
      Like Polypeptides.
AB  - The lower critical solution temperature (LCST) of the thermo-responsive
      engineered elastin-like polypeptide (ELP) biopolymer is being exploited for the
      thermal targeted delivery of doxorubicin (Dox) to solid tumors. We examine the
      impact of Dox labeling on the thermodynamic and hydrodynamic behavior of an ELP
      drug carrier and how Dox influences the liquid-liquid phase separation (LLPS).
      Turbidity, dynamic light scattering (DLS), and differential scanning calorimetry
      measurements show that ELP undergoes a cooperative liquid-liquid phase separation
      from a soluble to insoluble coacervated state that is enhanced by Dox labeling.
      Circular dichroism measurements show that below the LCST ELP consists of both
      random coils and temperature-dependent beta-turn structures. Labeling with Dox
      further enhances beta-turn formation. DLS measurements reveal a significant
      increase in the hydrodynamic radius of ELP below the LCST consistent with weak
      self-association. Dox-labeled SynB1-ELP1 (Dox-ELP) has a significant increase in
      the hydrodynamic radius by DLS measurements that is consistent with stable
      oligomers and, at high Dox-ELP concentrations, micelle structures. Enhanced
      association by Dox-ELP is confirmed by sedimentation velocity analytical
      ultracentrifugation measurements. Both ELP self-association and the ELP inverse
      phase transition are entropically driven with positive changes in enthalpy and
      entropy. We show by turbidity and DLS that the ELP phase transition is
      monophasic, whereas mixtures of ELP and Dox-ELP are biphasic, with Dox-labeled
      ELP phase changing first and unlabeled ELP partitioning into the coacervate as
      the temperature is raised. DLS reveals a complex growth in droplet sizes
      consistent with coalescence and fusion of liquid droplets. Differential scanning
      calorimetry measurements show a -11 kcal/mol change in enthalpy for Dox-ELP
      coacervation relative to the unlabeled ELP, consistent with droplet formation
      being stabilized by favorable enthalpic interactions. We propose that the ELP
      phase change is initiated by ELP self-association, enhanced by increased Dox-ELP
      oligomer and micelle formation and stabilized by favorable enthalpic interactions
      in the liquid droplets.

PMID- 30292394
TI  - RPS23RG1 Is Required for Synaptic Integrity and Rescues Alzheimer's Disease
      Associated Cognitive Deficits.
AB  - BACKGROUND: Although synaptic impairment is a prerequisite to cognitive
      deficiencies in Alzheimer's disease (AD), mechanisms underlying the dysregulation
      of essential synaptic scaffolding components and their integrity remain elusive.
      RPS23RG1 is a newly identified protein implicated in AD. However, the
      physiological function of RPS23RG1 has yet to be determined. METHODS: We
      investigated the role of RPS23RG1 in maintaining synaptic structure and function
      in cell cultures and in Rps23rg1 knockout mice and determined whether targeting
      RPS23RG1-mediated pathways has therapeutic potential in APP/PS1 AD model mice.
      RESULTS: Deletion of the Rps23rg1 gene resulted in severe memory deficits and
      impairment of postsynaptic structure and function, with marked reductions in
      postsynaptic densities-93 and -95 (PSD-93 and PSD-95) levels. RPS23RG1 interacted
      with PSD-93/PSD-95 through its intracellular domain, consequently sequestering
      PSD-93/PSD-95 from murine double minute 2-mediated ubiquitination and
      degradation, thereby maintaining synaptic function. Restoration of PSD-93/PS-D95
      levels reversed synaptic and memory deficits in Rps23rg1 knockout mice. We
      further observed attenuated RPS23RG1 expression in human AD, which positively
      correlated with PSD-93/PSD-95 levels. Importantly, an RPS23RG1-derived peptide
      comprising a unique PSD-93/PSD-95 interaction motif rescued synaptic and
      cognitive defects in Rps23rg1 knockout and AD mouse models. CONCLUSIONS: Our
      results reveal a role for RPS23RG1 in maintaining synaptic integrity and function
      and provide a new mechanism for synaptic dysfunction in AD pathogenesis. This
      demonstrates that RPS23RG1-mediated pathways show good therapeutic potential in
      AD intervention.

PMID- 30292395
TI  - Reversing Behavioral, Neuroanatomical, and Germline Influences of
      Intergenerational Stress.
AB  - BACKGROUND: Stressors affect populations exposed to them as well as offspring.
      Strategies preventing the intergenerational propagation of effects of stress
      would benefit public health. Olfactory cue-based fear conditioning provides a
      framework to address this issue. METHODS: We 1) exposed adult male mice to an
      odor, acetophenone (Ace) or Lyral (parental generation [F0]-Exposed), 2) trained
      mice to associate these odors with mild foot shocks (F0-Trained), and 3) trained
      mice to associate these odors with mild foot shocks and then extinguished their
      fear toward these odors with odor-only presentations (F0-Extinguished). We then
      examined sensitivity of future generation (F1) offspring to these odors,
      expression of M71 odorant (Ace-responsive) and MOR23 odorant (Lyral-responsive)
      receptor-expressing cell populations in F1 offspring, and DNA methylation at
      genes encoding the Ace- (Olfr151, Olfr160) and Lyral- (Olfr16) responsive
      receptors in F0 sperm. RESULTS: Extinguishing fear toward Ace or Lyral of F0 male
      mice (F0-Extinguished) that had been fear conditioned with Ace or Lyral,
      respectively, results in F1-Extinguished offspring that do not demonstrate
      behavioral sensitivity to Ace or Lyral, respectively, and do not have enhanced
      representation for M71 or MOR23 odorant receptors in the olfactory system, as is
      observed in F1-Trained-Ace or F1-Trained-Lyral cohorts, respectively. The
      promoters of genes encoding Olfr151 and Olfr160 receptors are less methylated in
      F0-Trained-Ace sperm compared with F0-Exposed-Ace sperm. The Olfr16 promoter is
      less methylated in F0-Trained-Lyral sperm compared with F0-Exposed-Lyral sperm,
      and F0-Extinguished-Lyral sperm have methylation levels comparable to F0-Exposed
      Lyral sperm. CONCLUSIONS: Our study demonstrates the potential of using
      extinction-based behavioral strategies to reverse influences of parental stress
      in offspring and in the parental germline.

PMID- 30292396
TI  - The relationship of elbow alignment and kinematics on shoulder torque during the
      softball pitch: a biomechanical analysis of female softball pitchers.
AB  - BACKGROUND: Female softball pitchers commonly throw more pitches per game and
      season than their baseball counterparts. The greatest stress to the shoulder
      during a softball windmill pitch is at ball release (BR). This study investigated
      shoulder torques at BR among female softball pitchers and identified
      relationships to the kinematics of the elbow and forearm and alignment of the
      elbow (carrying angle and elbow extension). METHODS: High-speed 3-dimensional
      biomechanical analyses were performed in 33 pitchers (25 high school, 8
      collegiate). Elbow and shoulder biomechanics at BR during fastball pitches and
      goniometric measures of carrying angle and elbow extension were collected and
      analyzed. RESULTS: Carrying angle correlated positively with shoulder extension
      torque at BR (rs = 0.371, P = .048) and forearm pronation at BR (rs = 0.370, P =
      .048). During the windmill pitch, the greater the elbow flexion, the greater
      shoulder adduction torque at BR (rs = -0.522, P = .007). Multiple regression
      analysis revealed that the carrying angle, passive elbow extension, and elbow
      flexion/extension angle at BR predicted shoulder flexion/extension torque at BR
      (F3,24 = 3.463, R2 = .302, P = .032.) CONCLUSIONS: Our findings demonstrate that
      shoulder torques during the softball fastpitch are influenced by the carrying
      angle and the kinematic elbow flexion angle at BR. Sports medicine clinicians and
      coaches should consider the role that the elbow carrying angle plays in creating
      shoulder stress when treating and training fastpitch softball players.

PMID- 30292397
TI  - Determining the in vitro susceptibility of Neisseria gonorrhoeae isolates from 8
      cities in Guangdong Province through an improved microdilution method.
AB  - A microdilution method for the antibiotic susceptibility testing of Neisseria
      gonorrhoeae was established and improved, and the antibiotic resistance of N.
      gonorrhoeae samples isolated from 8 cities of Guangdong in 2016 was determined.
      The improved microdilution method was compared with the agar dilution method
      recommend by the World Health Organization (WHO) Western Pacific Region by
      testing the susceptibility of 100 clinical N. gonorrhoeae isolates. The essential
      agreement (EA), categorical agreement (CA), very major error (VME), major error
      (ME), and minor error (MIE) levels of the two methods were analyzed; the
      acceptable performance rates were measured as follows: >=90% for EA or CA, <=3%
      for VME or ME, and <=7% for MIE. The EA, CA, VME, ME, and MIE of each method for
      7 antibiotics, penicillin, tetracycline, ciprofloxacin, spectinomycin,
      ceftriaxone, cefixime, and azithromycin, were 96%-100%, 94%-100%, 0%-3%, 0%-2%,
      and 0%-6%, respectively. The Wilcoxon signed-rank test results indicated 94%-100%
      agreement between the 2 methods after excluding off-scale values (P > 0.05). The
      susceptibility of 634 N. gonorrhoeae strains to the 7 antibiotics above were
      tested through the microdilution method. The resistant rates of the isolates
      against ciprofloxacin, tetracycline, penicillin, and azithromycin were 99.8%,
      88.3%, 53.8%, and 11%, and the percentages of the isolates with decreased
      susceptibility to ceftriaxone (minimum inhibitory concentration [MIC] >=0.125
      MUg/mL) and cefixime (MIC >=0.25 MUg/mL) were 2.1% and 12%, respectively, in
      Guangdong. Among 8 cities, Shenzhen had the highest rates of resistance against
      penicillin (77.8%) and decreased susceptibility against ceftriaxone (5.6%).
      Zhuhai had the highest rates of decreased susceptibility against cefixime
      (30.1%), and Jiangmen had the highest azithromycin-resistant isolates (16.8%).
      The findings from this study indicated that the improved microdilution method is
      an alternative for testing the antimicrobial susceptibility of N. gonorrhoeae.
      The resistance rates of N. gonorrhoeae against penicillin, tetracycline, and
      ciprofloxacin were high. While ceftriaxone, cefixime, and spectinomycin remained
      effective against N. gonorrhoeae, their effectiveness seemed to be decreasing
      over time. Azithromycin therapy requires timely susceptibility test results.

PMID- 30292398
TI  - Designed peptide with a flexible central motif from ranatuerins adapts its
      conformation to bacterial membranes.
AB  - The long-standing goal in the field of peptide antibiotics has been to design
      lead compounds that have a wide spectrum of excellent antibacterial activity but
      are nontoxic to human cells. Gram-negative and Gram-positive bacteria have very
      different membranes, which are additionally modified in some drug-resistant
      species, presenting a challenge for the design of a single membrane-active
      peptide able to adapt its conformation to various physical properties of membrane
      microenvironments. In this paper, we describe how a peptide sequence can be
      constructed starting from an adaptable dynamic turn tandem motif in a central
      location. The peptide, named flexampin, has been examined firstly by molecular
      dynamics simulations. It uses a flexible central motif and designed helix-forming
      cationic amphipathic arms to form a boomerang-like, L-shape, V-shape, and
      hairpin, super-secondary structures, whichever is the best in matching
      amphipathic and hydrophobic microenvironments it encounters. Secondly, activity
      measurements showed that flexampin is bactericidal at low micromolar
      concentrations against Gram-positive and Gram-negative strains including some
      multidrug resistant clinical isolates, while it is nontoxic for human circulating
      blood cells, does not cause DNA damage, and has good selectivity for bacterial
      cells in comparison to human cells. It is the first membrane-active peptide
      designed with the ability to self-adjust the orientation of its two cationic
      helical arms, 3D-hydrophobic moment, and dipole moment for obtaining a better
      grasp of anionic polar head groups at bacterial membrane surfaces.

PMID- 30292399
TI  - Effects of the peptide Magainin H2 on Supported Lipid Bilayers studied by
      different biophysical techniques.
AB  - Given the increasing trend in bacterial antibiotic resistance, research on
      antimicrobial peptides and their mechanisms of action has become of huge
      relevance in the last years. Several studies have investigated the effects of a
      large variety of antimicrobial peptides directly on bacteria or on model lipid
      bilayers. In the case of model lipid bilayers, different systems are typically
      exploited; however, different results could be obtained due to the specific
      properties of the used system. Supported Lipid Bilayers and Giant Unilamellar
      Vesicles are among the most popular model systems. Here we used Atomic Force
      Microscopy and fluorescence microscopy to study the interaction of the
      antimicrobial peptide Magainin H2, an analog of Magainin 2 with increased
      hydrophobicity, on Supported Lipid Bilayers. We found that, for this kind of
      model bilayer, due to its strong interaction with the support, the lateral
      expansion of the membrane induced by the interaction with the peptides is
      initially inhibited and subsequently proceeds creating new bilayer regions with
      many defects. This scenario gives rise in Supported Lipid Bilayers to effects
      like initial increase of lateral pressure, formation of lipid tubes to release
      this increase, or development of bilayer regions with lower lipid density. Our
      results highlight that care should be given to the selected model system when
      studying and comparing the interaction of peptides with other lipid bilayer model
      systems.

PMID- 30292400
TI  - Observer-based backstepping control method using reduced lateral dynamics for
      autonomous lane-keeping system.
AB  - This paper presents a backstepping control method with an augmented observer for
      an autonomous lane-keeping system. A novel reduced second-order model is also
      derived for an autonomous lane-keeping system. The proposed reduced model of
      lateral vehicle motion has the following advantages: (1) The lateral motion of
      the vehicle can be controlled with only simple linear second-order dynamics via
      the backstepping procedure; (2) The state variable of the reduced model includes
      the look-ahead distance similar to that for a human driver; (3) The system
      functions with unknown parameters and external disturbances can be lumped in the
      disturbance. An augmented observer is designed to estimate the full state and
      lumped disturbance, including the system functions with unknown parameters and
      external disturbances. A backstepping control is developed for improving the
      lateral control and compensation of the disturbance. The stability of the closed
      loop system is demonstrated using the input-to-state stable property. The lateral
      control performance of the proposed method is validated via numerical simulations
      using CarSim and MATLAB/Simulink.

PMID- 30292401
TI  - Comment on: Pneumonitis in advanced non-small-cell lung cancer patients treated
      with EGFR tyrosine kinase inhibitor: Meta-analysis of 153 cohorts with 15,713
      patients: Meta-analysis of incidence and risk factors of EGFR-TKI pneumonitis in
      NSCLC.

PMID- 30292402
TI  - Delivery of gynecologic oncology care: Optimizing scope of advanced practice
      providers to enhance patient care: A Society of Gynecologic Oncology Position
      Paper.

PMID- 30292403
TI  - Celebrating 20 years of support to people with epilepsy in Canada.

PMID- 30292404
TI  - Novel effect of sildenafil on hair growth.
AB  - BACKGROUND: Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, is known to
      increase the intracellular level of cyclic guanosine monophosphate (cGMP), which
      causes vasodilation. However, the effect of sildenafil on human hair follicles
      (hHFs) is unknown. OBJECTIVE: The purpose of this study was to determine the role
      of sildenafil in hair growth. METHODS: We investigated the expression of PDE5 in
      human dermal papilla cells (hDPCs) and hHFs. The effects of sildenafil on hDPC
      proliferation were evaluated using BrdU assays. The mRNA expression of growth
      factors and extracellular signal-regulated kinase (ERK) phosphorylation were
      investigated using real-time PCR and western blotting, respectively.
      Additionally, anagen induction and perifollicular vessel formation were evaluated
      using an in vivo mice model. RESULTS: We confirmed high expression of PDE5 in
      hDPCs and hHFs. Sildenafil enhances proliferation of hDPCs and up-regulates the
      mRNA expression of vascular endothelial growth factor (VEGF) and platelet-derived
      growth factor (PDGF), which are responsible for hair growth. Additionally,
      sildenafil up-regulates the levels of phosphorylated ERK and accelerates anagen
      induction by stimulating perifollicular vessel formation after topical
      application in mice. CONCLUSION: Our study demonstrates for the first time, the
      significant therapeutic potential of sildenafil on hair growth and its potential
      use in treatment of alopecia.

PMID- 30292405
TI  - MFSD2A expression predicts better prognosis in gastric cancer.
AB  - Major facilitator superfamily domain containing-2A (MFSD2A) is reported to
      correlated with some tumors, but its clinical significance in gastric cancer (GC)
      is still unknown. The expression of MFSD2A and CD34 were examined on tissue
      microarrays of 170 set of GC and adjacent normal tissue (ANT) by
      immunohistochemistry. The relationship of MFSD2A with microvessel density (MVD)
      and clinicopathological characteristics was also investigated. MFSD2A expression
      is lower in GC tissue (35.3%) than in ANT (78.2%, P < 0.01). Mean MVD was higher
      in cancer tissue (49.7 +/- 5.46) than in ANT (19.3 +/- 2.19, P < 0.01), and
      higher in MFSD2A- GC (56.5 +/- 7.27), than in MFSD2A+ GC (24.8 +/- 4.31, P <
      0.01). MFSD2A expression was significantly higher in moderately/well
      differentiated GC (47.4%) than in poorly differentiated GC (25.0%, P < 0.01) and
      in early-stage GC (46.4%) than in advanced GC (27.7%, P = 0.012). Patients with
      MFSD2A+ specimens (n = 60) had significantly better prognoses than the MFSD2A-
      group (n = 110; P < 0.0001). These results suggest that MFSD2A might affect
      angiogenesis and inhibit GC development and progression. MFSD2A may help predict
      prognosis and could be a therapeutic target in GC.

PMID- 30292406
TI  - Sterol regulatory element binding protein-1: Molecular cloning, tissue
      distribution and gene expression level in response to nutritional regulation in
      mud crab, Scylla paramamosain.
AB  - In the present study, SREBP-1 cDNA was cloned from the hepatopancreas of mud crab
      (Scylla paramamosain) and characterized by performing rapid-amplification of cDNA
      ends. The 3361bp long full-length cDNA encodes a polypeptide with 1039 amino
      acids. Tissue distribution analysis revealed that SREBP-1 transcripts were widely
      distributed in various organs, with higher mRNA levels in the eyestalk and
      cranial ganglia. Further, expression level of SREBP-1 mRNA were up-regulated in
      proportion to the replacement of dietary fish oil (FO) with soybean oil (SO).
      These results may contribute to better understanding of the long-chain
      polyunsaturated fatty acids (LC-PUFA) biosynthetic pathway and regulation
      mechanism in mud crab.

PMID- 30292407
TI  - MicroRNA-182-5p attenuates cerebral ischemia-reperfusion injury by targeting Toll
      like receptor 4.
AB  - Cerebral ischemia-reperfusion-induced microglial activation causes neuronal death
      through the release of inflammatory cytokines. Increasing evidence suggests that
      microRNAs (miRNAs) exert a neuroprotective effect by modulating the inflammatory
      process in cerebral ischemia-reperfusion injury. Furthermore, Toll-like receptor
      4 (TLR4) is increasingly being considered to have a significant role in the
      regulation of inflammation. However, whether miRNAs mediate their neuroprotective
      effects by regulating TLR4-mediated inflammatory responses remains unknown. To
      explore this gap in the literature, we conducted both in vitro and in vivo
      experiments. In vitro: BV2 cells were activated by oxygen-glucose deprivation
      (OGD). TLR4 and inflammatory cytokine (TNF-a, IL-6, and IL-1beta) transcription
      and translation expression levels were assessed using RT-PCR, ELISA, and western
      blot. BV2 cells were transfected with miR-182-5p mimics, inhibitors, siTLR4, or
      negative control (NC) using lipofectamine 2000 reagent. To confirm whether TLR4
      is a direct target of miR-182-5p, we performed a luciferase reporter assay. In
      BV2 cells, we observed that OGD upregulated TLR4 expression, but downregulated
      miR-182-5p expression. We determined that miR-182-5p inhibited TLR4 by directly
      binding to its 3'-UTR. Furthermore, miR-182-5p suppressed the release of TNF-a,
      IL-6, and IL-1beta. In vivo: A middle cerebral artery occlusion (MCAO) rat model
      was used to mimic cerebral ischemia-reperfusion. Iba1 and TLR4 double staining
      was used to demonstrate that the target of miR-182-5p in microglial cells, and
      the mediator of the anti-inflammatory effect, is TLR4. TTC staining was performed
      to evaluate the infarct volume. Compared to the animals treated with miR-182-5p
      NC and normal saline, rats treated with miR-182-5p mimics demonstrated
      significantly enhanced neurological functions. TTC staining results were
      consistent with neurological function test findings. In summary, our data
      suggested that miR-182-5p exhibits potential neuroprotective effects in the
      cerebral ischemia-reperfusion injury via the regulation of the TLR4-mediated
      inflammatory response.

PMID- 30292409
TI  - Development of trophoblast cystic structures from human induced pluripotent stem
      cells in limited-area cell culture.
AB  - We developed a novel engineering technique to induce differentiation of human
      induced pluripotent stem cells (hiPSCs) into organoids mimicking the
      trophectoderm (TE). Here, hiPSCs were cultured on a limited area of 2-4 mm in
      diameter. After 15-20 days, spherical cysts appeared on the surface of the
      limited area. Secretion of human chorionic gonadotrophin (hCG) began to increase
      after ~ 20 days and remained dramatically elevated over the next 20 days. Limited
      area-cultured cysts exhibited expression of hCG, which was a result of epithelial
      differentiation. Low expression levels of pluripotent genes and high expression
      levels of trophoblast lineage-specific genes were detected in the cells of
      spherical cysts. Multinucleated syncytia trophoblast was observed in the reseeded
      cystic cells. We observed hiPSC-derived cysts that morphologically resembled
      trophectoderm in vivo. The limited-area cell culture induced a three-dimensional
      (3D) trophectoderm organoid, which has potential for use in the study of human
      trophoblast differentiation and placental morphogenesis.

PMID- 30292408
TI  - Kin1 kinase localizes at the hyphal septum and is dephosphorylated by calcineurin
      but is dispensable for septation and virulence in the human pathogen Aspergillus
      fumigatus.
AB  - Studies in yeasts have implicated the importance of Kin1 protein kinase, a member
      of the eukaryotic PAR1/MARK/MELK family, in polarized growth, cell division and
      septation through coordinated activity with the phosphatase, calcineurin. Kin1 is
      also required for virulence of the fungal pathogens Cryptococcus neoformans and
      Fusarium graminearum. Here we show that kin1 deletion in the human fungal
      pathogen Aspergillus fumigatus does not affect hyphal growth and septation but
      results in differential susceptibility to antifungals targeting the cell wall and
      cell membrane. The Deltakin1 strain remained virulent in a Galleria mellonella
      model of invasive aspergillosis. Expression of Kin1 tagged to GFP or RFP showed
      its stable localization at the septum. Co-localization experiments revealed
      calcineurin (CnaA) localization on either side of Kin1 at the septum suggesting
      possible interaction. Bimolecular fluorescence complementation assay confirmed
      the interaction of Kin1 with CnaA at the hyphal tips and septa in the presence of
      the antifungal caspofungin. Furthermore, phosphoproteomic analyses for the first
      time revealed Kin1 as a substrate of calcineurin providing novel insight into
      Kin1 regulation through calcineurin-mediated dephosphorylation mechanism.

PMID- 30292410
TI  - Enhanced antitumor effect of combination of annexin A1 knockdown and bortezomib
      treatment in multiple myeloma in vitro and in vivo.
AB  - Bortezomib (BTZ) is one of the most frequently used drugs in treatment of
      multiple myeloma (MM), but drug-resistance often occurs and limits its clinical
      efficacy. Annexin A1 (ANXA1) is upregulated in MM, and its knockdown enhances
      chemosensitivity in MM. However, whether ANXA1 inhibition can increase antitumor
      activity of BTZ in MM cells remains unknown. In the present study, Cell Counting
      Kit-8 (CCK-8) and colony formation assays showed that ANXA1 silencing combined
      with BTZ treatment led to a more significant inhibition of MM cell proliferation
      than each treatment alone. Cell apoptosis was dramatically promoted in MM cells
      following silencing of ANXA1 and BTZ administration versus that in ANXA1-silenced
      alone or BTZ-treated alone cells, as evidenced by decreased expression of
      phosphorylated signal transducers and activators of transcription 3 and BCL2, and
      increased expression of BAX. Moreover, we demonstrated that the levels of IL-6
      and IL-23 were markedly downregulated in ANXA1-silenced and BTZ-treated MM cells.
      Furthermore, the combination of ANXA1 knockdown and BTZ treatment distinctly
      suppressed tumor growth in vivo compared with BTZ treatment alone. Taken
      together, our results show that downregulation of ANXA1 enhances antitumor
      activity of BTZ in MM in vitro and in vivo, indicating that ANXA1 may be a
      promising target for enhancing the chemosensitivity of MM to BTZ.

PMID- 30292411
TI  - A combination of irinotecan/cisplatinum and irinotecan/temozolomide or tumor
      targeting Salmonella typhimurium A1-R arrest doxorubicin- and temozolomide
      resistant myxofibrosarcoma in a PDOX mouse model.
AB  - Myxofibrosarcoma (MFS) is the most common sarcomas in elderly patients and is
      either chemo-resistant or recurs with metastasis after chemotherapy. This
      recalcitrant cancer in need of improved treatment. We have established a patient
      derived orthotopic xenograft (PDOX) of MFS. The MFS PDOX model was established in
      the biceps femoris of nude mice and randomized into 7 groups of 7 mice each:
      control; doxorubicin (DOX); pazopanib (PAZ); temozolomide (TEM); Irinotecan
      (IRN); IRN combined with TEM; IRN combined with cisplatinum (CDDP) and Salmonella
      typhimurium A1-R (S. typhimurium A1-R). Treatment was evaluated by relative tumor
      volume and relative body weight. The MFS PDOX models were DOX, PAZ, and TEM
      resistant. IRN combined with TEM and IRN combined with CDDP were most effective
      on the MFS PDOX. S. typhimurium A1-R arrested the MFS PDOX tumor. There was no
      significant body weight loss in any group. The present study suggests that the
      combination of IRN with either TEM or CDDP, and S. typhimurium have clinical
      potential for MFS.

PMID- 30292412
TI  - A role of GUNs-Involved retrograde signaling in regulating Acetyl-CoA carboxylase
      2 in Arabidopsis.
AB  - In Arabidopsis thaliana (Arabidopsis), Acetyl-CoA Carboxylase 2 (ACC2) is a
      nuclear DNA-encoded and plastid-targeted enzyme that catalyzes the conversion of
      acetyl-CoA to malonyl-CoA. ACC2 improves plant growth and development when
      chloroplast translation is impaired. However, little is known about the upstream
      signals that regulate ACC2. Here, through analyzing the transcriptome changes in
      brz-insensitive-pale green (bpg) 2-2, a pale-green mutant with impaired
      chloroplast gene expression resulting from loss of the BPG2 function, we found
      that the level of ACC2 was significantly up-regulated. Through performing genetic
      analysis, we further demonstrated that loss of the GENOMES UNCOUPLED 1 (GUN1) or
      GUN5 function partly perturbed the up-regulation of ACC2 in the bpg2-2 mutant,
      whereas ABA INSENSITIVE 4 (ABI4)-function-loss had no clear effect on the ACC2
      expression. Furthermore, when plants were treated with plastid translation
      inhibitors, such as lincomycin and spectinomycin, the ACC2 transcriptional level
      was also markedly increased in a GUN-dependent manner. In conclusion, our results
      suggested that the GUN-involved plastid-to-nucleus retrograde communication
      played a role in regulating ACC2 in Arabidopsis.

PMID- 30292414
TI  - LncRNA-CIR promotes articular cartilage degeneration in osteoarthritis by
      regulating autophagy.
AB  - Osteoarthritis (OA) is a common joint disease that is regarded as a local
      inflammatory response caused by joint instability and accompanied by the
      progressive degeneration of articular cartilage. However, the molecular
      mechanisms involved in the maintenance of articular cartilage remain a subject of
      debate and research. This study aims to analyze the roles of long noncoding RNA
      (lncRNA)CIR and autophagy in cartilages and determine their overall contribution
      to the degradation of extracellular matrix. Patients with OA possessed high
      levels of lncRNA-CIR and MMP3 and low level of COL2A1. The levels of autophagy
      related proteins, including LC3BI/II and beclin-1, increased from 12 h to 48 h.
      The use of si-lncRNA-CIR reversed the trend compared with that in the OA group.
      The negative effect of lncRNA-CIR was assessed in vivo by establishing a model of
      surgically induced OA. Moreover, si-lncRNA-CIR-treated joints exhibited fewer OA
      changes than saline-treated joints. Results were confirmed by histopathological
      grading of the models by using the Osteoarthritis Research Society International
      Scoring System and the outcomes of immunohistochemistry for LC3B-II and MMP-3.
      Overall, lncRNA-CIR played a negative role in the OA process by activating
      autophagy.

PMID- 30292413
TI  - Inflammatory production of reactive oxygen species by Drosophila hemocytes
      activates cellular immune defenses.
AB  - The production of reactive oxygen species (ROS) is a prominent response to
      infection among innate immune cells such as macrophages and neutrophils. To
      better understand the relationship between antimicrobial and regulatory functions
      of blood cell ROS, we have characterized the ROS response to infection in
      Drosophila hemocytes. Using fluorescent probes, we find a biphasic hemocyte ROS
      response to bacterial infection. In the first hour, virtually all hemocytes
      generate a transient ROS signal, with nonphagocytic cells including prohemocytes
      and crystal cells displaying exceptionally strong responses. A distinct, and more
      delayed ROS response starting at 90 min is primarily within cells that have
      engulfed bacteria, and is sustained for several hours. The early response has a
      clear regulatory function, as dampening or intensifying the intracellular ROS
      level has profound effects on plasmatocyte activation. In addition, ROS are
      necessary and sufficient to activate JNK signalling in crystal cells, and to
      promote JNK-dependent crystal cell rupture. These findings indicate that
      Drosophila will be a promising model in which to dissect the mechanisms of ROS
      stimulation of immune activation.

PMID- 30292415
TI  - Beneficial effects of anodal transcranial direct current stimulation (tDCS) on
      spatial working memory in patients with schizophrenia.
AB  - Schizophrenia is a severe and often detrimental psychiatric disorder. The
      individual patients' level of functioning is essentially determined by cognitive,
      particularly working memory (WM), deficits that are critically linked to
      dysfunctional activity of the dorsolateral prefrontal cortex (dlPFC).
      Transcranial direct current stimulation (tDCS) can transiently modulate activity
      of the dlPFC and remote areas and has been shown to improve WM functions. It may
      therefore provide a new, targeted treatment option. For this aim, the present
      study investigated the effect of anodal tDCS of different intensities on spatial
      WM in patients with schizophrenia. In two experiments, 32 patients performed a
      spatial n-back task with increasing WM load (1-, 2-, and 3-back) at baseline and
      in two sessions with anodal or sham tDCS (EXP I [n = 16]: 1 mA; EXP II [n = 16]:
      2 mA) to the right dlPFC (cathode: left m. deltoideus). With 1 mA anodal tDCS, no
      effect on WM performance could be detected. However, 2 mA anodal tDCS increased
      accuracy (measured by d') of the task with the highest WM load (3-back). This
      effect was larger in patients with a lower level of general neurocognitive
      functioning. These results demonstrate a beneficial effect of 2 mA anodal tDCS on
      deficient WM accuracy in patients with schizophrenia particularly under
      challenging conditions and in subjects with higher cognitive impairments. This
      data will inform future clinical trials on tDCS-enhanced cognitive training to
      improve treatment of schizophrenia.

PMID- 30292416
TI  - Role of conduct problems in the relation between Attention-Deficit Hyperactivity
      disorder, substance use, and gaming.
AB  - Known comorbidities for Attention-Deficit Hyperactivity Disorder (ADHD) include
      conduct problems, substance use disorder and gaming. Comorbidity with conduct
      problems may increase the risk for substance use disorder and gaming in
      individuals with ADHD. The aim of the study was to build a causal model of the
      relationships between ADHD and comorbid conduct problems, and alcohol, nicotine,
      and other substance use, and gaming habits, while accounting for age and sex. We
      used a state-of-the-art causal discovery algorithm to analyze a case-only sample
      of 362 ADHD-diagnosed individuals in the ages 12-24 years. We found that conduct
      problem severity mediates between ADHD severity and nicotine use, but not with
      more severe alcohol or substance use. More severe ADHD-inattentive symptoms lead
      to more severe gaming habits. Furthermore, our model suggests that ADHD severity
      has no influence on severity of alcohol or other drug use. Our findings suggest
      that ADHD severity is a risk factor for nicotine use, and that this effect is
      fully mediated by conduct problem severity. Finally, ADHD-inattentive severity
      was a risk factor for gaming, suggesting that gaming dependence has a different
      causal pathway than substance dependence and should be treated differently. By
      identifying these intervention points, our model can aid both researchers and
      clinicians.

PMID- 30292417
TI  - Stroke Epidemiology in Argentina. Design of a Population-Based Study in General
      Villegas (EstEPA).
AB  - BACKGROUND: Epidemiological data on stroke is scarce in Latin America. Estudio
      Epidemiologico Poblacional sobre Accidente Cerebrovascular (EstEPA) is a
      population-based program planned to assess prevalence, incidence, mortality, and
      burden of disease for stroke in the Department of General Villegas, province of
      Buenos Aires, Argentina. METHODS AND DESIGN: Prevalence study will consist of a
      two-phase survey approach in the urban area of General Villegas. First, trained
      social workers with a structured questionnaire will collect data in 2000 randomly
      selected housing units. Those subjects screened positive for possible strokes
      will be interviewed and examined by stroke neurologists to confirm diagnosis. The
      incidence study will be performed according to the methodology of WHO STEPS
      stroke surveillance manual and will detect all new strokes in the department
      during a 5-year period. General and disease-specific mortality rates will be
      assessed monthly during a 5-year period, using different sources of information.
      To assess the overall burden of cerebrovascular disease, disability adjusted life
      years will be calculated. DISCUSSION: EstEPA will assess for the first time all
      aspects of stroke epidemiology in Argentina. Its results will help to implement
      population-based interventions and to properly allocate public health resources.

PMID- 30292418
TI  - Multidisciplinary treatment of lung cancer in older patients: A review.
AB  - Lung cancer is the leading cause of cancer death worldwide. Older patients
      represent approximately half of the patient population and optimal management of
      these patients is challenging. In early-stagenon-small cell lung cancer (NSCLC),
      lobectomy should be considered in fit older patients. For unfit patients,
      stereotactic body radiotherapy (SBRT) represents a good alternative. While data
      on the benefit and risk of concurrent chemo-radiotherapy (cCRT) in older patients
      with locally advanced NSCLC is conflicting, age alone should not preclude cCRT.
      Multidisciplinary collaboration is essential for appropriate patient selection.
      In limited disease small cell lung cancer (SCLC), older patients appear to
      benefit similarly from standard treatment compared to their younger counterparts,
      however, with a higher risk of toxicity. Appropriately selected older patients
      with lung cancer seem to derive as much benefit from active oncological treatment
      as their younger counterparts. Geriatric screening tests and comprehensive
      geriatric assessments (CGA) can be helpful when choosing between treatment
      strategies. Older patients are at risk for under-treatment; this should be
      avoided by proper selection and multidisciplinary management. This review
      outlines the management of lung cancer in older patients.

PMID- 30292419
TI  - Modern Management of the Failed Bladder Exstrophy Closure: A 50-yr Experience.
AB  - BACKGROUND: A failed closure of classic bladder exstrophy (CBE) has a negative
      long-term impact on the patient and the health care system. OBJECTIVE: To
      investigate the outcomes of CBE patients with failed primary bladder closure.
      DESIGN, SETTING, AND PARTICIPANTS: A database of 1317 exstrophy-epispadias
      complex patients was retrospectively reviewed for CBE patients with failed
      primary bladder closure from 1965 to 2017 with subsequent repeat closure.
      INTERVENTION: Repeat bladder exstrophy closure and subsequent continence
      procedure. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Failed exstrophy
      closures are defined as occurrence of bladder prolapse, dehiscence,
      vesicocutaneous fistula, outlet obstruction, or combination of these factors.
      Successful repeat closures are defined as closures that require no further
      operative intervention as a consequence of these factors. Kaplan-Meier to
      determine time to successful repeat closure and receiver operator characteristic
      curve to determine the optimal time for secondary closure were determined.
      RESULTS AND LIMITATIONS: In total, 170 CBE patients had at least one repeat
      closure following a failed primary closure (115 male/55 female). With continued
      closure attempts, 166/170 (97.6%) patients were successfully closed. The median
      time to successful closure from birth was 12.9 mo (95% confidence interval: 11.7
      15.7). Furthermore, 52/153 (34%) patients had more than one osteotomy. Of 215
      total osteotomies, 50 (29.4%) were performed during the 170 failed primary
      closures, 128 (75.3%) during the 170second closures, and 27 (64.3%) during the 42
      third closures. Of 96 patients with available continence data, 74 (77.1%)
      achieved urinary continence. CONCLUSIONS: A successful repeat closure is
      possible, especially when used in conjunction with a pelvic osteotomy. Continent
      urinary diversion yielded the highest continence rate in this cohort. PATIENT
      SUMMARY: We looked at outcomes of classic bladder exstrophy closure in a large
      population. Successful repeat closure is possible in the majority of cases when
      used with pelvic osteotomy. A majority of patients achieved urinary continence
      using a continent diversion.

PMID- 30292420
TI  - Current Evidence on Nonantibiotic Prevention of Recurrent Urinary Tract
      Infections.
AB  - Clinicians should be aware of the limited evidence on nonantibiotic prophylactic
      treatment for recurrent urinary tract infections. Owing to the rising antibiotic
      resistance rates worldwide, nonantibiotic prevention strategies should be
      considered for patient care. Further research is necessary to evaluate
      nonantibiotic treatment strategies using a robust randomised controlled trial
      methodology to contribute to a strong evidence basis.

PMID- 30292421
TI  - Metastases-yield and Prostate-specific Antigen Kinetics Following Salvage Lymph
      Node Dissection for Prostate Cancer: A Comparison Between Conventional Surgical
      Approach and Prostate-specific Membrane Antigen-radioguided Surgery.
AB  - : The first results on 99mTechnetium prostate-specific membrane antigen
      radioguided surgery (99mTc-PSMA- RGS) showed promising outcome. Here, we sought
      to evaluate if this targeted molecular surgical approach might be more effective
      than conventional salvage lymph node dissection (sLND). We prospectively analysed
      42 consecutive patients who underwent sLND based on preoperative 68Gallium (68Ga)
      PSMA-positron emission tomography (PET) imaging between 2015 and 2018. In 29
      patients, the dissection field was based solely 68Ga-PSMA-PET imaging
      (conventional surgical approach [CSA]), whereas 13 patients underwent 99mTc-PSMA
      RGS. Preoperative characteristics of both groups were similar. Final pathology
      revealed no metastases in nine CSA patients (31%), whereas all visible lesions on
      preoperative 68Ga-PSMA-PET were removed in patients who underwent RGS. A PSA
      decline in general, >50% and >90% within 6 wk was seen in 50%, 29%, and 7% versus
      100%, 92%, and 53% in CSA versus RGS groups, respectively (all p<0.01). This is
      the first comparison of conventional and PSMA-radioguided approach with regards
      to short-term efficacy of sLND. Although long-term outcome needs to be awaited,
      RGS offers promising results. PATIENT SUMMARY: We compared two surgical
      approaches for lymph node dissection in lymph node only recurrent prostate cancer
      patients. The radioguided approach was superior in removing the affected lymph
      nodes, resulting in a more pronounced prostate-specific antigen decline.

PMID- 30292422
TI  - Prostatic Artery Embolization versus Standard Surgical Treatment for Lower
      Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Systematic
      Review and Meta-analysis.
AB  - CONTEXT: Prostatic artery embolization (PAE) has been introduced into clinical
      practice for the treatment of lower urinary tract symptoms secondary to benign
      prostatic hyperplasia (BPH-LUTS) despite a lack of high-level evidence.
      OBJECTIVE: To perform a systematic review and meta-analysis of clinical trials
      comparing efficacy and safety of PAE versus established surgical therapies.
      EVIDENCE ACQUISITION: Medline, Embase, and York CRD were searched up to June 23,
      2018. Only comparative studies were included. The risk of bias was assessed by
      the Cochrane Collaboration tool. Meta-analyses were performed using RevMan 5.3.
      EVIDENCE SYNTHESIS: Five studies including 708 patients met the selection
      criteria. Risk of bias was rated high for most of the studies. Mean reduction in
      the International Prostate Symptom Score was lower after PAE compared with
      standard surgical therapies (mean difference 3.80 points [95% confidence
      interval: 2.77-4.83]; p<0.001). PAE was less efficient regarding improvements in
      all functional parameters assessed including maximum urinary flow, post void
      residual, and reduction of prostate volume. In contrast, patient-reported
      erectile function (International Index of Erectile Function 5) was better after
      PAE and significantly fewer adverse events occurred after PAE. CONCLUSIONS:
      Moderately strong evidence confirms efficacy and safety of PAE in the treatment
      of BPH-LUTS in the short term. Significant advantages regarding safety and sexual
      function, but clear disadvantages regarding all other patient-reported and
      functional outcomes were found for PAE. Large-scale randomized controlled trials
      including longer follow-up periods are mandatory before PAE can be considered as
      a standard therapy and to define the ideal indication for PAE in the management
      of BPH-LUTS. PATIENT SUMMARY: We reviewed the role of prostatic artery
      embolization (PAE) in the treatment of symptoms associated with benign overgrowth
      of the prostate. The results suggest that PAE is not as effective as established
      surgical therapies but has fewer side effects. Further research is required to
      determine whether PAE is the best treatment for certain types of patients. PAE
      should, therefore, not yet be considered a standard treatment.

PMID- 30292424
TI  - Facing obesity: Adapting the collaborative deliberation model to deal with a
      complex long-term problem.
AB  - OBJECTIVE: Care communication about obesity needs to respond to the complex
      biopsychosocial processes that affect weight and health. The collaborative
      deliberation model conceptualizes interpersonal work that underpins empathic
      communication and shared decision-making. The goal of this study was to elucidate
      how primary care practitioners can use the model to achieve shared obesity
      assessment and care planning. METHODS: This qualitative study used direct
      observation of clinical encounters with twenty patients with obesity sampled for
      maximum variation in context, semi-structured patient and provider interviews,
      patient journals and two follow-up interviews over eight weeks. Themes were
      compared to the original model. RESULTS: We identified five processes that may be
      relevant for collaborative deliberation about obesity in addition to the original
      model: (1) Exploring the story, (2) Reframing the story, (3) Co-constructing a
      new story, (4) Choosing a priority, and (5) Experimenting with alternatives.
      CONCLUSIONS: We propose an enhanced collaborative deliberation model for obesity
      that describes the interpersonal work needed before and after deliberation about
      preferences and courses of action. PRACTICE IMPLICATIONS: The enhanced model can
      support clinicians in achieving meaningful conversations about obesity and
      complex chronic disease resulting in care plans that are responsive to and
      achievable in the patient's lifeworld.

PMID- 30292423
TI  - Biocompatible bacteria-derived vesicles show inherent antimicrobial activity.
AB  - Up to 25,000 people die each year from resistant infections in Europe alone, with
      increasing incidence. It is estimated that a continued rise in bacterial
      resistance by 2050 would lead up to 10 million annual deaths worldwide, exceeding
      the incidence of cancer deaths. Although the design of new antibiotics is still
      one way to tackle the problem, pharmaceutical companies investigate far less into
      new drugs than 30 years ago. Incorporation of antibiotics into nanoparticle drug
      carriers ("nanoantibiotics") is currently investigated as a promising strategy to
      make existing antibiotics regain antimicrobial strength and overcome certain
      types of microbial drug resistance. Many of these synthetic systems enhance the
      antimicrobial effect of drugs by protecting antibiotics from degradation and
      reducing their side effects. Nevertheless, they often cannot selectively target
      pathogenic bacteria and - due to their synthetic origin - may induce side-effects
      themselves. In this work, we present the characterisation of naturally derived
      outer membrane vesicles (OMVs) as biocompatible and inherently antibiotic drug
      carriers. We isolated OMVs from two representative strains of myxobacteria,
      Cystobacter velatus Cbv34 and Sorangiineae species strain SBSr073, a bacterial
      order with the ability of lysing other bacterial strains and currently
      investigated as sources of new secondary metabolites. We investigated the
      myxobacterias' inherent antibacterial properties after isolation by differential
      centrifugation and purification by size-exclusion chromatography. OMVs have an
      average size range of 145-194 nm. We characterised their morphology by electron
      cryomicroscopy and found that OMVs are biocompatible with epithelial cells and
      differentiated macrophages. They showed a low endotoxin activity comparable to
      those of control samples, indicating a low acute inflammatory potential. In
      addition, OMVs showed inherent stability under different storage conditions,
      including 4  degrees C, -20  degrees C, -80  degrees C and freeze-drying. OMV
      uptake in Gram-negative model bacterium Escherichia coli (E. coli) showed similar
      to better incorporation than liposome controls, indicating the OMVs may interact
      with model bacteria via membrane fusion. Bacterial uptake correlated with
      antimicrobial activity of OMVs as measured by growth inhibition of E. coli. OMVs
      from Cbv34 inhibited growth of E. coli to a comparable extent as the clinically
      established antibiotic gentamicin. Liquid-chromatography coupled mass
      spectrometry analyses revealed the presence of cystobactamids in OMVs, inhibitors
      of bacterial topoisomerase currently studied to treat different Gram-negative and
      Gram-positive pathogens. This work, may serve as an important basis for further
      evaluation of OMVs derived from myxobacteria as novel therapeutic delivery
      systems against bacterial infections.

PMID- 30292425
TI  - 'Breast cancer won't kill ya in the breast': Broaching a rationale for
      chemotherapy during the surgical consultation for early-stage breast cancer.
AB  - OBJECTIVE: To examine how, and for what interactional purpose, a surgeon raises
      the risk of death with an early-stage breast cancer patient. METHOD: Single-case
      analysis of a recorded surgical consultation, using conversation analysis.
      RESULTS: The surgeon not only negotiates the surgical treatment decision with the
      patient, she provides an overview of what her non-surgical treatment is likely to
      entail. Analysis reveals how the surgeon addresses interactional challenges when
      providing this overview, including how to broach the rationale for administering
      chemotherapy, the possibility that cancer could spread to vital organs and prove
      fatal. To do this, the surgeon orients to the possibility that the patient has
      misconceptions about her risk of dying from breast cancer. She uses negatively
      formulated assertions to invoke these possible misconceptions, making correction
      relevant and providing a point of entry into delicate interactional territory.
      CONCLUSION: The surgeon draws upon possible patient misconceptions to broach the
      rationale for administering adjuvant chemotherapy. PRACTICE IMPLICATIONS: The
      surgical consultation is typically the first treatment-related consultation newly
      diagnosed breast cancer patients have and represents an opportunity to educate
      patients and prepare them for future treatment decisions. The challenges of
      providing and receiving such overviews, and how they may influence future
      treatment decisions, merit consideration.

PMID- 30292426
TI  - Pharmacologic Treatment of Intensive Care Unit Delirium and the Impact on
      Duration of Delirium, Length of Intensive Care Unit Stay, Length of
      Hospitalization, and 28-Day Mortality.
AB  - OBJECTIVE: To determine whether treatment of delirium affects outcomes. PATIENTS
      AND METHODS: A retrospective cohort study of patients admitted to the medical
      intensive care unit (ICU) from July 1, 2015, through June 30, 2016, was
      conducted. Patients with ICU delirium, defined by a positive Confusion Assessment
      Method for the ICU score, were included. Patients were stratified into 4
      treatment groups based on exposure to melatonin and antipsychotic agents during
      ICU stay: no pharmacologic treatment, melatonin only, antipsychotics only, and
      both melatonin and antipsychotics. A time-dependent cause-specific hazards model
      with death as a competing risk was used to evaluate the effect of melatonin or
      antipsychotic drug use for delirium on duration of ICU delirium, length of ICU
      stay, and length of hospitalization. A logistic regression was used to evaluate
      28-day mortality. Covariates significantly associated with exposure to melatonin
      and antipsychotics were included in the minimally adjusted model. Covariates
      significantly associated in the minimally adjusted model were included in a final
      adjusted model. RESULTS: A total of 449 admissions to the medical ICU were
      included in the analysis. Exposure to melatonin or antipsychotic agents did not
      reduce the duration of ICU delirium, ICU/hospital length of stay, or 28-day
      mortality. However, antipsychotic use only was associated with longer
      hospitalization. CONCLUSION: Antipsychotic drugs for the treatment ICU delirium
      may not provide the benefit documented in earlier literature. Further
      investigation on patient selection, type of antipsychotic, and dosing is needed.

PMID- 30292427
TI  - India's escalating burden of non-communicable diseases.

PMID- 30292428
TI  - Effect of sildenafil citrate treatment in the eNOS knockout mouse model of fetal
      growth restriction on long-term cardiometabolic outcomes in male offspring.
AB  - Fetal growth restriction (FGR) is associated with an increased risk of
      hypertension, insulin resistance, obesity and cardiovascular disease in
      adulthood. Currently there are no effective treatments to reverse the course of
      FGR. This study used the eNOS knockout mouse (eNOS-/-), a model of FGR, to
      determine the ability of sildenafil, a potential new treatment for FGR, to
      improve cardiovascular and metabolic outcomes in adult offspring following a
      complicated pregnancy. Pregnant eNOS-/- and C57BL/6J control dams were randomised
      to sildenafil treatment (0.2 mg/ml in drinking water) or placebo at day 12.5 of
      gestation until birth. After weaning, male offspring were randomised to either a
      high fat (HFD; 45% kcal from fat) or normal chow diet (ND), and raised to either
      postnatal day 90 or 150. Growth and body composition, glucose tolerance, insulin
      resistance, systolic blood pressure and vascular function were analysed at both
      time-points. eNOS-/- offspring were significantly smaller than their C57BL/6J
      controls at weaning and P90 (p < 0.01); at P150 they were a similar weight. Total
      adipose tissue deposition at P90 was significantly increased only in eNOS-/- mice
      fed a HFD (p < 0.001). At P150 both C57BL/6J and eNOS-/- offspring fed a HFD
      demonstrated significant adipose tissue deposition (p < 0.01), regardless of
      maternal treatment. Both diet and maternal sildenafil treatment had a significant
      effect on glucose tolerance. Glucose tolerance was significantly impaired in eNOS
      /- mice fed a HFD (p < 0.01); this was significant in offspring from both
      sildenafil and vehicle treated mothers at P90 and P150. Glucose tolerance was
      also impaired in C57BL/6J mice fed a HFD at both P90 and P150 (p < 0.01), but
      only in those also exposed to sildenafil. In these C57BL/6J mice, sildenafil was
      associated with impaired insulin sensitivity at P90 (p = 0.020) but increased
      insulin resistance at P150 (p = 0.019). Exposure to sildenafil was associated
      with a significant increase in systolic blood pressure in eNOS-/- mice compared
      with their C57BL/6J diet controls at P150 (p < 0.05). Exposure to sildenafil had
      differing effects on vascular function in mesenteric arteries; it increased
      vasodilation in response to ACh in C57BL/6J mice, but was associated with a more
      constrictive phenotype in eNOS-/- mice. eNOS-/- mice demonstrate a number of
      impaired outcomes consistent with programmed cardiometabolic disease,
      particularly when faced with the 'second hit' of a HFD. Exposure to sildenafil
      treatment during pregnancy did not increase fetal growth or significantly improve
      adult metabolic or cardiac outcomes. Maternal sildenafil treatment was, however,
      associated with small impairments in glucose handling and an increase in blood
      pressure. This study highlights the importance of understanding the long-term
      effects of treatment during pregnancy in offspring from both complicated and
      healthy control pregnancies.

PMID- 30292429
TI  - Leptin and insulin do not exert redundant control of metabolic or emotive
      function via dopamine neurons.
AB  - Leptin and insulin's hunger-suppressing and activity-promoting actions on
      hypothalamic neurons are well characterized, yet the mechanisms by which they
      modulate the midbrain dopamine system to influence energy balance remain less
      clear. A subset of midbrain dopamine neurons express receptors for leptin (Lepr)
      and insulin (Insr). Leptin-dopamine signaling reduces running reward and homecage
      activity. However, dopamine-specific deletion of Lepr does not affect body weight
      or food intake in mice. We hypothesized insulin-dopamine signaling might
      compensate for disrupted leptin-dopamine signaling. To investigate the degree to
      which insulin and leptin exert overlapping (i.e. redundant) versus discrete
      control over dopamine neurons, we generated transgenic male and female mice
      exhibiting dopamine-specific deletion of either Lepr (Lepr KO), Insr (Insr KO) or
      both Lepr and Insr (Dbl KO) and assessed their feeding behavior, voluntary
      activity, and energy expenditure compared to control mice. No differences in body
      weight, daily food intake, energy expenditure or hyperphagic feeding of palatable
      chow were observed between Lepr, Insr or Dbl KO mice and control mice. However,
      consistent with previous findings, Lepr KO (but not Insr or Dbl KO) male mice
      exhibited significantly increased running wheel activity compared to controls.
      These data demonstrate that insulin and leptin do not exert redundant control of
      dopamine neuron-mediated modulation of energy balance. Furthermore, our results
      indicate neither leptin nor insulin plays a critical role in the modulation of
      dopamine neurons regarding hedonic feeding behavior or anxiety-related behavior.

PMID- 30292430
TI  - Senescent Cells Drive Frailty through Systemic Signals.
AB  - Senescent cells drive ageing and the associated loss in health and lifespan.
      Whether this is mediated by systemic signalling remained unclear. Recently, Xu et
      al. [1] (Nat. Med. 2018;24:1246-1256) answered this question by injecting
      senescent cells into young mice and observing a long-lasting increase in frailty
      and mortality.

PMID- 30292431
TI  - Ecological Function Analysis: Incorporating Species Roles into Conservation.
AB  - Effective conservation strategies must ensure that species remain not just
      extant, but able to maintain key roles in species interactions and in the
      maintenance of communities and ecosystems. Such ecological functions, however,
      have not been well incorporated into management or policy. We present a framework
      for quantifying ecological function that is complementary to population viability
      analysis (PVA) and that allows function to be integrated into strategic planning
      processes. Ecological function analysis (EFA) focuses on preventing secondary
      extinctions and maintaining ecosystem structure, biogeochemical processes, and
      resiliency. EFA can use a range of modeling approaches and, because most species
      interactions are relatively weak, EFA needs to be performed for relatively few
      species or functions, making it a realistic way to improve conservation
      management.

PMID- 30292433
TI  - Foreword.

PMID- 30292432
TI  - Bridge to recovery in children on ventricular assist devices-protocol, predictors
      of recovery, and long-term follow-up.
AB  - BACKGROUND: The majority of children supported with ventricular assist devices
      (VADs) are bridged to heart transplantation. Although bridge to recovery has been
      reported, low recovery patient numbers has precluded systematic analysis. The aim
      of this study was to delineate recovery rates and predictors of recovery and to
      report on long-term follow-up after VAD explantation in children. METHODS:
      Children bridged to recovery at our institution from January 1990 to May 2016
      were compared with a non-recovery cohort. Clinical and echocardiographic data
      before and at pump stoppages and after VAD explantation were analyzed. Kaplan
      Meier estimates of event-free survival, defined as freedom from death or
      transplantation after VAD removal, were determined. RESULTS: One hundred forty
      nine children (median age 5.8 years) were identified. Of these, 65.2% had
      cardiomyopathy, 9.4% had myocarditis, and 24.8% had congenital heart disease. The
      overall recovery rate was 14.2%, and was 7.1% in patients with dilated
      cardiomyopathy. Predictors of recovery were age <2 years (recovery rate 27.8%,
      odds ratio [OR] 5.64, 95% confidence interval [CI] 2.0 to 16.6) and diagnosis of
      myocarditis (rate 57.1%; OR 17.56, 95% CI 4.6 to 67.4). After a median follow-up
      of 10.8 years, 15 patients (83.3%) were in Functional Class I and 3 (16.7%) in
      were in Class II. Mean left ventricular ejection fraction was 53% (range 28% to
      64%). Ten- and 15-year event-free survival rates were both 84.1 +/- 8.4%.
      CONCLUSIONS: Children <2 years of age and those diagnosed with myocarditis have
      the highest probability of recovery. Long-term survival after weaning from the
      VAD was better than after heart transplantation, as demonstrated in the excellent
      long-term stability of ejection fraction and functional class.

PMID- 30292434
TI  - Prognostic value of dual imaging stress echocardiography following coronary
      bypass surgery.
AB  - AIMS: To assess the prognostic value of dual imaging stress echocardiography
      after coronary artery bypass grafting (CABG). Dual imaging stress
      echocardiography, combining the evaluation of regional wall motion and Doppler
      echocardiographic derived coronary flow velocity reserve (CFVR) of the left
      anterior descending artery (LAD), is the state-of-the-art methodology during
      vasodilatory stress. METHODS AND RESULTS: In a prospective, multicenter,
      observational study, 349 patients (270 men; 69 +/- 9 years; 262 symptomatic) with
      history of CABG underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress
      echocardiography with CFVR evaluation of LAD by Doppler. The composite endpoint
      of death and myocardial infarction was considered in the survival analysis.
      Positivity rate with either criteria was 13% in the 262 symptomatic patients with
      appropriate and 6% in the 87 asymptomatic patients with maybe/rarely appropriate
      indications on the basis of 2014 American College of Cardiology Foundation
      guidelines. During a median follow-up of 22 months (1st quartile 8, 3rd quartile
      44), there were 56 (16%) events: 21 deaths, and 35 nonfatal myocardial
      infarctions. At Cox analysis, ischemia at stress echo (HR 4.80, 95% CI 2.69-8.55;
      p < 0.0001), and CFVR of LAD <=2 (HR 2.28, 95% CI 1.32-3.95; p = 0.003) were
      multivariable prognostic predictors. Considering the group with no ischemia,
      patients with CFVR <=2 showed 2.5 fold higher yearly hard events as compared to
      those with CFVR >2 (7.5 vs 2.9%; p = 0.002). CONCLUSIONS: Dual imaging stress
      echocardiography provides useful prognostic information following CABG. Inducible
      ischemia and abnormal CFVR are strong and independent prognostic indicators in
      patients with appropriate and rarely/maybe appropriate indications.

PMID- 30292435
TI  - Prevalence and significance of T-wave inversion in children practicing sport: A
      prospective, 4-year follow-up study.
AB  - BACKGROUND: T-wave inversion (TWI) is rare in athlete's heart but is a common
      manifestation in cardiomyopathies. Although TWI has been extensively investigated
      in adult athletes, the ability of this ECG pattern to distinguish between a
      physiological variant and a developing heart muscle disease in children is
      controversial. The aim of this longitudinal study was to establish the
      prevalence, changes and clinical significance of TWI in a large cohort of pre
      adolescent athletes. METHODS: 2227 children (mean age 12.3 +/- 2.0 years)
      undergoing sports preparticipation screening were included. Children with TWI
      underwent yearly follow-up until the positivisation of TWI for a maximum follow
      up of 4 years. RESULTS: Among 2227 children, 358 (16%) had TWI. Children with TWI
      were younger (11.4 +/- 2.1 vs. 12.5 +/- 2.0 years, p < 0.0001) and had a lower
      BSA than children without TWI (p < 0.0001). 97% of children showed anterior TWI
      while only 3% had infero-lateral TWI. Anterior TWI became positive in 94% of
      children during the 4-year follow-up (p < 0.0001 vs. baseline) and the remaining
      6% did not show abnormal clinical findings. Conversely, in the group of 9
      children with infero-lateral TWI, only 1 showed normalisation during follow-up (p
      = 0.81) and 1 was found to have a cardiomyopathy. CONCLUSIONS: Anterior TWI is
      common in children and generally becomes positive by the age of 14 years.
      Conversely, infero-lateral TWI is rare, persistent and may be associated with
      structural heart disease. Therefore, infero-lateral TWI should not be interpreted
      as physiologically related to age, development or training and children with
      infero-lateral TWI should remain under strict clinical surveillance.

PMID- 30292436
TI  - Chest pain in the absence of obstructive coronary artery disease: A critical
      review of current concepts focusing on sex specificity, microcirculatory
      function, and clinical implications.
AB  - Patients presenting with chest pain suggestive of coronary artery disease (CAD)
      who at coronary arteriography appear to be free of obstructive disease have
      presented a diagnostic and therapeutic challenge since the 1970's. Studies in
      female patient populations have suggested that this is predominantly a women's
      syndrome usually caused by microvascular endothelial dependent and independent
      dysfunction. A critical review of the literature focusing on studies including
      both women and men revealed that apart from a higher incidence of this syndrome
      in women there are no clinical relevant differences between both sexes. In women
      a lower coronary flow reserve has been reported but this appears to be mainly due
      to a higher basal flow. Important questions with regard to the clinical
      implications of microvascular dysfunction have yet to be resolved in studies
      involving women as well as men in which a distinction is made between patients
      with normal coronary arteries and those with nonobstructive disease.

PMID- 30292437
TI  - Using Bayesian methods to update and expand the meta-analytic evidence of the
      five-factor model's relation to antisocial behavior.
AB  - The Five Factor Model (FFM) of personality is the dominant hierarchical model of
      personality. Previous work has demonstrated the importance of the FFM domains and
      facets in understanding a variety of antisocial behaviors ranging from non
      violent antisocial behavior to a variety of aggression outcomes. The aim of the
      present meta-analysis was to quantitatively summarize the empirical work that has
      examined these relations, as well as update and expand previous work in this area
      using Bayesian meta-analytic methods. A comprehensive search of available
      literature on the FFM and antisocial behavior was conducted and posterior
      distributions of effect sizes were computed for the FFM domains (across 12
      antisocial outcomes). The meta-analytic results supported the primary importance
      of (low) Agreeableness and (low) Conscientiousness in predicting antisocial
      behavior across antisocial outcomes, with the exception of the outcome related to
      child molestation. The importance of Neuroticism was more dependent on the
      specific antisocial outcome under examination. The results are discussed in the
      context of the descriptive research on the FFM and antisocial behavior, and how
      Bayesian methods provide additional utility in estimation and prediction compared
      to more common frequentist methods. Furthermore, we recommend that future work on
      the FFM and antisocial behavior move towards process-level analyses to further
      examine how traits are implicated in different forms of antisocial behavior.

PMID- 30292438
TI  - The psychology of Tourette disorder: Revisiting the past and moving toward a
      cognitively-oriented future.
AB  - Tourette syndrome is a neurodevelopmental disorder characterized by chronic tics
      (i.e., repetitive and stereotyped movements and vocalizations) and premonitory
      urges (i.e., aversive sensations preceding tics that are alleviated once a tic is
      performed). Research supports that dysfunctional neurobiological and
      psychological processes interact and contribute to the development and
      maintenance of tics. However, psychological theories of Tourette syndrome and
      accompanying research have mainly focused on the emotional states (e.g., anxiety
      and frustration) and behavioural principles (i.e., operant conditioning) that
      play a role in tic exacerbation. This selective review summarizes key discoveries
      pertaining to the emotional and behavioural aspects of Tourette syndrome but also
      proposes a more comprehensive, cognitively-oriented conceptualization of the
      disorder. Specifically, it is proposed that maladaptive beliefs about discomfort
      and about one's ability to cope with discomfort underlie negative appraisals of
      unpleasant sensory experiences in individuals with Tourette syndrome. It is
      further suggested that these beliefs lead individuals to perceive premonitory
      urges in a catastrophic manner and thereby enhance tic frequency. Concrete
      research avenues to empirically examine these hypotheses are outlined and
      clinical implications for the field of cognitive-behaviour therapy are discussed.

PMID- 30292439
TI  - Diversity in randomized clinical trials of depression: A 36-year review.
AB  - Historically, authors reporting the results of randomized clinical trials (RCTs)
      to address mental health problems have insufficiently described sample
      characteristics pertaining to the ethnic/racial, linguistic, socioeconomic, and
      immigrant backgrounds of participants. RCTs have also had inadequate
      representation of participants from diverse backgrounds. This study reports on
      the trends in the reporting and representation of various sample demographic
      characteristics in RCTs of psychotherapy and other psychosocial interventions for
      depression over a 36-year period, and on the extent to which ethnicity, in
      particular, is considered in the analyses of treatment effects. A total of 342
      trials (85.1% comprised of adult samples), representing 61,283 participants, are
      summarized in the review. Reporting for ethnicity and socioeconomic indicators
      improved over time, and RCTs for depression have also increasingly included
      significant numbers of ethnic minority and low-income groups. However, trials are
      far more likely to exclude, rather than include, linguistic minorities, and have
      not enrolled a meaningful number of Asian American, Native Hawaiian/Pacific
      Islander, Native American/Native Alaskan and multi-ethnic participants. Finally,
      treatment effects are almost never presented separately across racial/ethnic
      groups and ethnicity moderation analyses are only sporadically conducted. These
      findings have implications for generalizability, policy, journal reporting
      guidelines, and dissemination and implementation.

PMID- 30292440
TI  - Improving HIV Preexposure Prophylaxis Implementation for Women: Summary of Key
      Findings From a Discussion Series With Women's HIV Prevention Experts.

PMID- 30292441
TI  - [Prescription of furosemide in general medicine in Aquitaine: Prospective
      practice survey among universities general practitioners].
AB  - OBJECTIVES: Furosemide is essential in the management of patients with congestive
      heart failure, and provides important iatrogenic complications. We described the
      prescription of this treatment in general medicine, and tried to identify areas
      for optimizing its use. PATIENTS AND METHOD: We carried out a prospective
      inventory of the prescription of furosemide with the general practitioners of the
      universities of Bordeaux, between May 1, 2017 and July 30, 2017. RESULTS: We
      obtained data from 119 prescriptions of furosemide. The indications seemed well
      known, largely dominated by heart failure (67%) and its associated signs (24%).
      Clinical and biological follow-up (52%) and therapeutic education (42%) seemed
      relatively infrequent. CONCLUSIONS: Our study confirms the central role of the
      general practitioner in the prescription of furosemide, the predominant place of
      heart failure in its indications and the iatrogeny observed. We identified areas
      of optimization of the safety and effectiveness of the treatment. The
      reinforcement of training concerning heart failure and its treatments, a better
      communication between specialties, the implementation of reference systems
      dedicated to the prescription of furosemide and prescription support software
      seem promising.

PMID- 30292442
TI  - [Prevention - cardiac rehabilitation: The same fight!]

PMID- 30292443
TI  - [Demographic evolution, clinical characteristics and in-hospital outcomes of
      older adults treated by primary angioplasty for ST-segment elevation myocardial
      infarction].
AB  - BACKGROUND: The number of older adults treated for ST-segment elevation
      myocardial infarction (STEMI) is increasing. Nevertheless, their treatment might
      not be as optimal as younger adults. This study sought to evaluate demographic
      evolution, clinical characteristics and in-hospital outcomes of patients of
      patients aged 75years-old or older treated by primary angioplasty for STEMI.
      METHODS: Retrospective study of all consecutive patients for STEMI between
      January 2012 and December 2017. Their clinical, biologic, echocardiographic and
      angiographic data, as well as in-hospital outcomes were collected and compared
      between two groups: younger and older than 75 year-olds. RESULTS: Five hundred
      and sixty-eight patients including 99 (17.4%) 75 year-old or older were included
      in the present study. Patients aged 75 or older had an increased delay of
      treatment between the time of the chest pain onset and revascularization (7.30+/
      1,16 vs 4.77+/-0,36hours, P=0.0391), they were more frequently treated with
      clopidogrel rather than more potent anti P2Y12 antiplatelet therapies (55.6% vs
      24.8%, P<0.0001) and received less frequently anti-GP2B3A therapy (44.8% vs
      23.2%, P<0.0001). There was a trend for increased in-hospital mortality in the
      older group, despite non statistically significant (4.04% vs 1.5%, P=0.0847).
      Older adults had a worse clinical status with decreased post-STEMI left
      ventricular ejection fraction (44.42+/-1,38 vs 49.07+/-0,49, P=0,0019). They were
      also less treated with drug-eluting stents (51.5% vs 73.9%, P<0.0001).
      CONCLUSION: Adults aged 75 years-old or older represent a subsequent proportion
      of patients admitted for STEMI. They had a worse initial clinical presentation
      associated with worse prognostic, as compared to younger adults. They experience
      delayed reperfusion therapy and suboptimal treatment as compared to younger
      adults.

PMID- 30292444
TI  - [Evaluation of the management of low-risk pulmonary embolism diagnosed in an
      emergency department. HoPE study (Home treatment of Pulmonary Embolism)].
AB  - INTRODUCTION: Risk stratification allows outpatient management of low-risk
      pulmonary embolism (PE). Here, we carry out an evaluation of the professional
      practices on the emergency management of low-risk PE, after selection with the
      sPESI score. MATERIAL AND METHOD: All patients admitted to the emergency
      department of Chambery hospital, with a final diagnosis of PE are analyzed. The
      PE of score sPESI at 0 are included, in the absence of contraindications. Ninety
      day follow-up is done. The objective is to evaluate the proportion of ambulatory
      care for low-risk patients. RESULTS: Eighty PE were diagnosed in 2016, 28 with
      sPESI score at 0 and 3 patients excluded. Of the 25 inclusions, 6 patients had
      signs of right ventricular dysfunction and were therefore hospitalized. The
      remaining 19 were eligible for outpatient care but only 8 of them stayed less
      than 24hours in the hospital. DISCUSSION: The sPESI score is a decision support
      tool for outpatient management but should not be used alone. The search for right
      ventricular dysfunction seems important here.

PMID- 30292445
TI  - [Management and prognosis of pulmonary embolism associated with right heart
      thrombi: A prospective study at the University Hospital Yalgado Ouedraogo].
AB  - OBJECTIVE: To describe the management and evolution of high risk of death
      pulmonary embolism associated with right heart thrombi. MATERIAL AND METHODS: We
      conducted a prospective cohort survey over a 54 month-period, from March 1st,
      2012 to September 30th 2015. Were included all patients with pulmonary embolism
      and having high or intermediate-high risk of death. Patients were divided into
      two groups according to whether cardiac Doppler-echography found a thrombus in
      the right chambers or not (ICT+ vs. ICT-). The survival curves for the patients
      were obtained using the software STATA. RESULTS: The prevalence of pulmonary
      embolism associated with right heart thrombi was 4% in our study. Thrombi were
      mobile, straight localization in all cases. The ICT+group was characterized by a
      significantly higher proportion of congestive heart and chronic lung disease. The
      proportion of patients' thrombolysis was significantly higher in the ICT-group.
      In the ICT+group, thrombolysis significantly reduced mortality giving a 30-day
      survival of 80% against 20% among patients receiving only heparin. CONCLUSION:
      Pulmonary embolism associated with right heart thrombi including the atrium are
      not exceptional. These patients are at high risk of early death. Thrombolysis is
      significantly improving the mortality of pulmonary embolism associated with right
      sided heart thrombi.

PMID- 30292446
TI  - Microdeletion 22q11.2 syndrome: Does thymus incidental surgical resection affect
      its immunological profile?
AB  - BACKGROUND: The del22q11 syndrome patients present immunological abnormalities
      associated to thymus alterations. Up to 75% of them present cardiopathies and
      thymus is frequently removed during surgery. The thymectomy per se has a
      deleterious effect concerning lymphocyte subpopulations, and T cell function.
      When compared to healthy controls, these patients have higher infections
      propensity of variable severity. The factors behind these variations are unknown.
      We compared immunological profiles of del22q11.2 Syndrome patients with and
      without thymectomy to establish its effect in the immune profile. METHODS: Forty
      six del22q11.2 syndrome patients from 1 to 16 years old, 19 of them with partial
      or total thymectomy were included. Heart disease type, heart surgery, infections
      events and thymus resection were identified. Immunoglobulin levels, flow
      cytometry for lymphocytes subpopulations and TREC levels were determined, and
      statistical analyses were performed. RESULTS: The thymectomy group had a lower
      lymphocyte index, both regarding total cell count and when comparing age-adjusted
      Z scores. Also, CD3+, CD4+ and CD8+ lower levels were observed in this group, the
      lowest count in those patients who had undergone thymus resection during the
      first year of life. Their TREC level median was 23.6/MUL vs 16.1MUL in the non
      thymus group (p=0.22). No differences were identified regarding immunoglobulin
      levels or infection events frequencies over the previous year. CONCLUSION:
      Patients with del22q11.2 syndrome subjected to thymus resection present lower
      lymphocyte and TREC indexes when compared to patients without thymectomy. This
      situation may be influenced by the age at the surgery and the time elapsed since
      the procedure.

PMID- 30292447
TI  - Osteoprotegerin mediate RANK/RANKL signaling inhibition eases asthma inflammatory
      reaction by affecting the survival and function of dendritic cells.
AB  - INTRODUCTION: Asthma is a chronic inflammatory, heterogeneous airway disease
      affecting millions of people around the world. Dendritic cells (DCs) are
      considered the most important antigen-presenting cell in asthma airway
      inflammatory reaction. But whether osteoprotegerin (OPG) mediate RANK/RANKL
      signaling inhibition influences asthma development by affecting the survival and
      function of DCs remains unclear. In this study, we assessed the effects of OPG on
      DCs and asthma. MATERIAL AND METHODS: BALB/c mice immunized with ovalbumin (OVA)
      were challenged thrice with an aerosol of OVA every second day for eight days.
      Dexamethasone (1.0mg/kg) or OPG (50MUg/kg) was administered intraperitoneally to
      OVA-immunized BALB/c mice on day 24 once a day for nine days. Mice were analyzed
      for effects of OPG on asthma, inflammatory cell infiltration and cytokine levels
      in lung tissue. The expression of RANK and beta-actin was detected by Western
      Blot. DCs were isolated from mouse bone morrow. Cell survival was assessed by
      cell counting. The content of IL-12 was detected by ELISA. RESULTS: Results
      showed that OVA increased the number of inflammatory factors in BALF, elevated
      lung inflammation scores in mice. OPG reversed the alterations induced by OVA in
      the asthmatic mice. OPG inhibited the survival and function of DC via inhibition
      of RANK/RANKL signaling. CONCLUSIONS: This research proved inhibition of
      RANK/RANKL signaling by OPG could ease the inflammatory reaction in asthma,
      providing new evidence for the application of OPG on asthma.

PMID- 30292448
TI  - Widening the antimicrobial spectrum of esters of bicyclic amines: In vitro effect
      on gram-positive Streptococcus pneumoniae and gram-negative non-typeable
      Haemophilus influenzae biofilms.
AB  - Antibiotic resistance is a global current threat of increasing importance.
      Moreover, biofilms represent a medical challenge since the inherent antibiotic
      resistance of their producers demands the use of high doses of antibiotics over
      prolonged periods. Frequently, these therapeutic measures fail, contributing to
      bacterial persistence, therefore demanding the development of novel
      antimicrobials. Esters of bicyclic amines (EBAs), which are strong inhibitors of
      Streptococcus pneumoniae growth, were initially designed as inhibitors of
      pneumococcal choline-binding proteins on the basis of their structural analogy to
      the choline residues in the cell wall. However, instead of mimicking the
      characteristic cell chaining phenotype caused by exogenously added choline on
      planktonic cultures of pneumococcal cells, EBAs showed an unexpected lytic
      activity. In this work we demonstrate that EBAs display a second, and even more
      important, function as cell membrane destabilizers. We then assayed the
      inhibitory and disintegrating activity of these molecules on pneumococcal
      biofilms. The selected compound (EBA 31) produced the highest effect on S.
      pneumoniae (encapsulated and non-encapsulated) biofilms at very low
      concentrations. EBA 31 was also effective on mixed biofilms of non-encapsulated
      S. pneumoniae plus non-typeable Haemophilus influenzae, two pathogens frequently
      forming a self-produced biofilm in the human nasopharynx. These results support
      the role of EBAs as a promising alternative for the development of novel, broad
      range antimicrobial drugs encompassing both Gram-positive and Gram-negative
      pathogens.

PMID- 30292449
TI  - Implications of the transcription factor WT1 linked to the pathologic cardiac
      remodeling post-myocardial infarction.
AB  - New advances in the treatment of acute myocardial infarction involve novel
      signaling pathways and cellular progeny. In this sense, regeneration is a novel
      tool that would contribute to post-infarction physiological ventricular
      remodeling. More specifically, re-expression of the WT1 transcription factor in
      the myocardial wall by ischemia and infarction would be related to the invasion
      of cells with the capacity for regeneration. This mechanism seems not to be
      sufficient to restore muscle cells and lost vessels entirely. Of particular
      interest, the presence of the heat-shock response protein 70 (Hsp70) and its
      interaction with the vitamin D receptor would modulate the expression of WT1
      positively. In this context, it is proposed that the activation of vitamin D
      receptors associated with Hsp70 could favor physiological cardiac remodeling and
      reduce the progression to heart failure.

PMID- 30292450
TI  - TRalpha inhibits arterial renin-angiotensin system expression and prevents
      cholesterol accumulation in vascular smooth muscle cells.
AB  - OBJECTIVES: The tissue renin-angiotensin system (tRAS) plays a key role in the
      maintenance of cellular homeostasis but is also implicated in atherosclerosis.
      Thyroid hormone (TH) contributes, via genomic effects, to control of tRAS gene
      expression in the arterial wall and vascular smooth muscle cells (VSMCs). We
      investigated the specific functions of TH receptors-alpha and -beta (TRalpha and
      TRbeta) on tRAS gene expression in the aorta and VSMCs, and the potential
      protective effect of TRalpha against atherosclerosis. MATERIAL AND METHODS: Using
      aorta and cultured aortic VSMCs from TRalpha and TRbeta deficient mice, tRAS gene
      expression was analyzed by determining mRNA levels on real-time PCR. Gene
      regulation under cholesterol loading mimicking atherosclerosis conditions was
      also examined in VSMCs in vitro. RESULTS: TRalpha deletion significantly
      increased expression of angiotensinogen (AGT) and angiotensin II receptor type 1
      subtype a (AT1Ra) at transcriptional level in aorta, a tissue with high TRalpha
      expression level. TRalpha activity thus seems to be required for maintenance of
      physiological levels of AGTand AT1Raexpression in the arterial wall. In addition,
      during cholesterol loading, TRalpha deletion significantly increased cholesterol
      content in VSMCs, with a weaker decrease in AGTexpression. CONCLUSION: TRalpha
      seems to have an inhibitory impact on AGTand AT1Raexpression, and loss of TRalpha
      function in TRalpha0/0 mice increases tRAS expression in the aortic wall. More
      importantly, TRalpha deletion significantly increases VSMC cholesterol content.
      Our results are consistent with a protective role of TRalpha against
      atherosclerosis.

PMID- 30292451
TI  - Outcomes of Vital Pulp Therapy Using Mineral Trioxide Aggregate or Biodentine: A
      Prospective Randomized Clinical Trial.
AB  - INTRODUCTION: Mineral trioxide aggregate (MTA) has been used in pulp capping of
      cariously exposed mature permanent teeth with promising results. The search for
      alternative materials that seal better and set faster than MTA and do not stain
      is ongoing. Biodentine (Septodont, St Maur-des-Fosses, France) exhibits these
      advantages but has not been tested yet for a prolonged duration in mature teeth.
      This study aimed to evaluate the clinical performance of Biodentine and white MTA
      (Angelus, Londrina, Brazil) in cariously exposed mature permanent teeth. METHODS:
      This was a prospective longitudinal randomized controlled study of 68 vital
      permanent teeth with deep caries. Patients were randomly allocated into 2 study
      arms: Biodentine and MTA. Teeth were assessed clinically and radiographically
      before the procedure. Caries were excavated under local anesthesia; hemostasis
      was achieved after pulp exposure using sodium hypochlorite and capped with
      Biodentine or MTA. Clinical and radiographic follow-ups were performed by a
      blinded calibrated evaluator after 6 months and 1, 2, and 3 years. RESULTS: There
      were no significant differences in the overall success rate between Biodentine
      and MTA; it was 93.3% (Biodentine = 93.1% and MTA = 93.5%) at 6 months. The
      overall success rate increased to 96.2% (Biodentine = 96.0% and MTA = 100%) at 1
      year and to 100% at 2 years. At the 3-year follow-up, it decreased to 93.8%
      (Biodentine = 91.7% and MTA = 96.0%). CONCLUSIONS: Biodentine and MTA have
      favorable and comparable success rates when used as direct pulp capping or
      pulpotomy material in permanent mature teeth with carious exposure. The remaining
      tooth structure and durability of coronal restoration might affect significantly
      the long-term success of vital pulp therapy.

PMID- 30292452
TI  - Lymphaticovenous bypass of the thoracic duct for the treatment of chylous leak in
      central conducting lymphatic anomalies.
AB  - BACKGROUND: Central conducting lymphatic anomalies (CCLA) may cause chylous leaks
      and protein-losing enteropathy (PLE) owing to dysfunction of the central
      lymphatic channels. Most of the treatment strategies for these conditions are
      palliative and provide transient improvement. METHODS: We treated 14 patients
      with intractable chylous leak and/or PLE using a novel technique of
      lymphaticovenous bypass of the terminal portion of the thoracic duct. Chylous
      leaks occurred in multiple different anatomic sites. All patients had CCLA and
      failure of thoracic duct emptying demonstrated by preoperative intranodal
      lymphangiography. RESULTS: Five patients had complete resolution of symptoms, and
      two patients had partial improvement. There were no major complications. Of 5
      patients with PLE, only one improved after lymphaticovenous bypass. Repeat
      traditional lymphangiography was performed in 4 patients who did not improve,
      demonstrating patency of the bypass in all cases with persistent sluggish
      drainage. One patient had repeat MR lymphangiography that did not show the
      thoracic duct well. CONCLUSIONS: Bypass of the terminal thoracic duct is a novel
      procedure that offers improvement and a chance of cure for some patients with
      devastating manifestations of CCLA who lack other effective therapeutic options.
      LEVEL OF EVIDENCE: IV.

PMID- 30292453
TI  - Using Individual Clinical Evaluations to Assess Residents' Clinical Judgment;
      Feasibility and Residents' Perception.
AB  - OBJECTIVE: In surgical training, most assessment tools focus on advanced clinical
      decision-making or operative skill. Available tools often require significant
      investment of resources and time. A high stakes oral examination is also required
      to become board-certified in surgery. We developed Individual Clinical Evaluation
      (ICE) to evaluate intern-level clinical decision-making in a time- and cost
      efficient manner, and to introduce the face-to-face evaluation setting. DESIGN:
      Intern-level ICE consists of 3 clinical scenarios commonly encountered by
      surgical trainees. Each scenario was developed to be presented in a step-by-step
      manner to an intern by an attending physician or chief resident. The interns had
      17 minutes to complete the face-to-face evaluation and 3 minutes to receive
      feedback on their performance. The feedback was transcribed and sent to the
      interns along with incorrect answers. Eighty percent correct was set as a minimum
      to pass each scenario and continue with the next one. Interns who failed were
      retested until they passed. Frequency of incorrect response was tracked by
      question/content area. After passing the 3 scenarios, interns completed a survey
      about their experience with ICE. SETTING: Beth Israel Deaconess Medical Center,
      an academic tertiary care facility located in Boston, Massachusetts.
      PARTICIPANTS: All first-year surgery residents in our institution (n = 17) were
      invited to complete a survey. RESULTS: All 2016-2017 surgical interns (17)
      completed the ICEs. A total of $171 (US) was spent conducting the ICEs, and an
      average of 17 minutes was used to complete each evaluation. In total, 5 different
      residents failed 1 scenario, with the most common mistake being: failing to
      stabilize respiration before starting management. After completing the 3 clinical
      scenarios, more than 90% of respondents agreed or strongly agreed that the
      evaluations were appropriately challenging for training level, and that the
      evaluations helped to identify personal strengths and weaknesses in skill and
      knowledge. The majority believed their knowledge improved as a result of the ICE
      and felt better prepared to manage these scenarios (88% and 76%, respectively).
      CONCLUSIONS: The ICE is an inexpensive and time efficient way to introduce
      interns to board type examinations and assess their preparedness for
      perioperative patient care issues. Common errors were identified which were able
      to inform educational efforts. ICEs were well accepted by residents. Next steps
      include extension of the ICE to PGY2 and PGY3 residents.

PMID- 30292454
TI  - Self-debriefing Model Based on an Integrated Video-Capture System: An Efficient
      Solution to Skill Degradation.
AB  - OBJECTIVE: Video-based teaching is considered highly effective in debriefing,
      especially in minimally invasive surgeries. In this study, the benefits of using
      a new integrated video recording system, were investigated and compared to those
      of the standard basic skills robotic training procedure. DESIGN: Fifty residents
      from the 2nd and 3rd year medical faculty without any experience of robot usage
      or laparoscopy were randomized into 2 groups: group A--a natural self-training
      group without a trainer, and group B--a self-training group assisted by an
      integrated video recording system during training. The training was divided into
      four 2-hour sessions, with a 72-hour delay between each session. Two tasks were
      selected for testing on the dV-Trainer, a virtual reality based robotic
      simulator: Match board 2 and Thread the Rings 1. After each session, the practice
      video recorded by the system of group B was transferred to the residents'
      smartphones for self-debriefing. At the end of each session, the performance
      score was evaluated automatically by using the simulator to plot learning curves
      A and B. RESULTS: Group A showed a significant drop in performance score due to
      skill decay caused by the 72-hour delay. Group B exhibited a regular stepwise
      rising learning curve. At the end of the training, group B showed a significantly
      higher performance score both in Match board 2 and Thread the Rings 1. The
      autoanalysis and capture function, which selects only the critical errors and
      most valuable parts, could facilitate time saving. CONCLUSIONS: The use of an
      integrated video recording system makes the self-manipulated protocol with own
      smartphone feasible to improve training efficiency and overcome the skill decay
      during robotic surgical training.

PMID- 30292455
TI  - Corrigendum to "Simulation studies to assess the long-term effects of Japan's
      change from trivalent to quadrivalent influenza vaccination" [Vaccine 36 (2018)
      624-630].

PMID- 30292457
TI  - Response to Morimoto and Takeishi 2018.

PMID- 30292456
TI  - Antigenic and sequence variability of the human respiratory syncytial virus F
      glycoprotein compared to related viruses in a comprehensive dataset.
AB  - A comprehensive analysis of sequence variation was carried out comparing the
      fusion (F) protein of human respiratory syncytial viruses (hRSV) from antigenic
      groups A and B with the prototype sequence of the A2 strain, also belonging to
      antigenic group A. The limited number of full bovine RSV F sequences available
      were included, as well as an extensive set of F sequences from the related human
      metapneumovirus (hMPV). The results were analysed in the context of the recently
      determined three dimensional F protein structures, with antigenic sites mapped to
      these. Although a high degree of sequence conservation in hRSV F exists, and
      sequence changes did not correlate with location of antigenic sites, preferential
      accumulation of amino acid changes in certain antigenic sites was noted. When the
      analysis was extended to hMPV F, a high number of changes was noticed, in
      agreement with the limited degree of sequence conservation. However, some
      conserved regions were noted, which may account for the limited number of cross
      reactive monoclonal antibodies described between hRSV F and hMPV F. These results
      provide information about the degree of sequence and antigenic variation
      currently found in the F protein of circulating viruses. They highlight the
      importance of establishing a baseline dataset to monitor for future changes that
      might evolve should preventative immunological measures be made widely available.

PMID- 30292458
TI  - Increasing trend in invasive non-typeable Haemophilus influenzae disease and
      molecular characterization of the isolates, Italy, 2012-2016.
AB  - Routine immunization of infants with conjugate vaccines against Haemophilus
      influenzae type b (Hib) has greatly reduced the incidence of invasive Hib
      disease; however changes in the epidemiology of H. influenzae disease have
      occurred. We describe the epidemiology of invasive H. influenzae disease and the
      characterization of isolates collected in Italy between 2012 and 2016. Trends in
      the overall incidence of invasive H. influenzae disease were calculated. Isolates
      were characterized by PCR capsular genotyping, antimicrobial susceptibility
      testing, ampicillin resistance-associated gene sequencing and MLST. Trends in
      incidence by serotype and serotype-specific distribution were estimated using
      multiple imputation of missing data. The overall incidence of invasive H.
      influenzae disease increased 22.5% yearly (from 0.11/100,000 in 2012 to
      0.24/100,000 in 2016). Most cases (82.0%) were due to non-typeable H. influenzae
      (NTHi). An increasing trend in NTHi disease burden was estimated; the highest
      rise was among infants <12 months (40.8% annual increase). Invasive Hib disease
      showed a fluctuating trend with a clear increase in 2016, while we found an
      increasing trend for disease due to non-Hib capsulated serotypes in the elderly
      (32.9% annual increase). Ampicillin resistance mediated by either beta-lactamase
      or altered penicillin-binding proteins 3 (PBP3) increased. In spite of genetic
      diversity of NTHi, sequence types (STs) associated with ampicillin resistance
      status were identified (ST103/ST106 linked to beta-lactamase production and ST14
      linked to a specific PBP3 substitution pattern). The increasing trend in invasive
      NTHi disease in infants is of concern underlying the need for the development of
      a future vaccine against NTHi.

PMID- 30292459
TI  - Mesenchymal stromal cells: an opportunity to treat chronic inflammatory
      intestinal conditions.

PMID- 30292460
TI  - Comparison of Patient Position and Midline Lumbar Neuraxial Access Via
      Statistical Model Registration to Ultrasound.
AB  - Patient positioning and needle puncture site are important for lumbar neuraxial
      anesthesia. We sought to identify optimal patient positioning and puncture sites
      with a novel ultrasound registration. We registered a statistical model to
      volumetric ultrasound data acquired from volunteers (n = 10) in three positions:
      (i) prone; (ii) seated with thoracic and lumbar flexion; and (iii) seated as in
      position ii, with a 10 degrees  dorsal tilt. We determined injection target size
      and penetration success by simulating lumbar injections on validated registered
      models. Injection window and target area sizes in seated positions were
      significantly larger than those in prone positions by 65% in L2-3 and 130% in L3
      4; a 10 degrees  tilt had no significant effect on target sizes between seated
      positions. In agreement with computed tomography studies, simulated L2-3 and L3-4
      injections had the highest success at the 50% and 75% midline puncture sites,
      respectively, measured from superior to inferior spinous process. We conclude
      that our registration to ultrasound technique is a potential tool for tolerable
      determination of puncture site success in vivo.

PMID- 30292461
TI  - Enhancement Patterns of Intrahepatic Cholangiocarcinoma on Contrast-Enhanced
      Ultrasound: Correlation with Clinicopathologic Findings and Prognosis.
AB  - To evaluate the correlations between the enhancement pattern of intrahepatic
      cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) and
      clinicopathologic findings and prognosis, a retrospective study was performed on
      197 patients with mass-forming ICC who underwent pre-operative CEUS and surgical
      resection. The contrast medium we employed in CEUS was SonoVue, which contains
      microbubbles consisting of sulfur hexafluoride bubbles within a phospholipid
      shell. This study was approved by the institutional review board with informed
      consent waived. Patients were classified into an arterial rim-like enhancement
      group or an arterial non-rim-like enhancement group, and arterial enhancement
      patterns were correlated with clinicopathologic factors. Overall survival (OS)
      times were calculated using the Kaplan-Meier method, and differences between
      groups were compared with the log-rank test. Univariate and multivariate Cox
      regression models for OS were used to evaluate the independent prognostic
      factors. The mean and range of ICC tumor size of the arterial rim-like group
      (59.41 +/- 22.09 mm, 20-100 mm) were similar to those of the arterial non-rim
      like group (59.82 +/- 30.35 mm, 14-162 mm, p = 0.914). Arterial enhancement
      patterns were correlated with chronic viral hepatitis or cirrhosis, vascular
      invasion, lymph node metastasis and single/multiple tumors. A total of 78
      patients (39.6%) exhibited arterial rim-like enhancement, and the other 119
      patients (60.4%) exhibited arterial non-rim-like enhancement. Arterial
      enhancement pattern (p = 0.045), vascular invasion (p = 0.005), lymph node
      metastasis (p = 0.000) and number of tumors (p = 0.001) were independent
      prognostic factors for OS. The arterial non-rim-like enhancement pattern of ICC
      on CEUS is an independent prognostic factor for better OS and may offer new
      information for predicting the prognosis of ICC patients before surgical
      resection.

PMID- 30292462
TI  - Non-linear Wave Propagation and Safety Standards for Diagnostic Ultrasound
      Devices.
AB  - Safety standards for clinical diagnostic ultrasonic devices were developed for
      use in relatively low-frequency systems (1-10 MHz), under the assumption that non
      linear effects would be negligible. This article reviews ways in which neglecting
      non-linear wave propagation affects the measurements and calculations required to
      comply with safety standards and U.S. Food and Drug Administration guidance that
      recognizes these standards. An attempt is made to evaluate whether ignoring non
      linear effects could result in significant error in the exposure quantities
      defined in these standards at either low or high frequencies, based on published
      literature. This article maintains that although non-linear effects have been
      considered in some parts of safety standards related to hydrophone requirements,
      the coverage is inadequate, especially for modern equipment with high working
      frequencies. A new approach is required to assess the magnitude of thermal
      heating for recently developed high-frequency systems to incorporate non-linear
      effects. In contrast, the current approach for evaluating the risk of cavitation
      can be used after appropriate modifications.

PMID- 30292463
TI  - Evolution of the antibiotic-resistance of microorganisms causing urinary tract
      infections: A 4-year epidemiological surveillance study in a hospital population.
AB  - BACKGROUND: Urinary tract infections (UTIs) are the leading cause of infection in
      hospitalised patients. In this study, we describe the most common pathogens
      involved in the development of UTIs in hospitalised patients, their antibiotic
      sensitivity profile and the activity evolution of antibiotics in standard use for
      treating these infections. METHODS: We retrospectively assessed the results of
      cultures and antibiograms from urine samples from adult patients hospitalised in
      the Hospital Complex Virgen de la Nieves (Granada, Spain) with a microbiological
      confirmation of UTI between January 2013 and December 2016. RESULTS: We
      identified 4,347 microorganisms (3,969 bacteria and 378 yeasts). During the
      4years of the study, Escherichia coli was the most common species isolated in
      both sexes; however, 62.9% of the UTIs were caused by other microorganisms. The
      presence of multiresistant microorganisms such as Acinetobacterspp. (1.2%) and
      extended-spectrum beta-lactamase-producing enterobacteria (10.0%) and
      carbapenemase-producing enterobacteria (0.3%) were also relevant findings.
      Imipenem, piperacillin-tazobactam and fosfomycin presented activity rates above
      80%, considering all causal microorganisms of UTI, while the other tested
      antibiotics presented activity rates below 70%. CONCLUSION: Imipenem and
      piperacillin-tazobactam were the most active antibiotics in hospital use, which
      makes them first-line antibiotics in the empiric treatment of UTIs in this
      healthcare setting. The use of other antibiotics should be limited to conditions
      of demonstrated or highly probable sensitivity.

PMID- 30292464
TI  - RiHHTa, a Spanish clinical registry as an example of networked multicentre
      activities for a rare disease.

PMID- 30292465
TI  - Evaluating the Impact of the Venous Thromboembolism Outcome Measure on the PSI 90
      Composite Quality Metric.
AB  - INTRODUCTION: Patient Safety Indicator (PSI) 90 is a composite measure widely
      used in federal pay-for-performance and public reporting programs. A component
      metric of PSI 90, venous thromboembolism (VTE) rate, has been shown to be subject
      to surveillance bias and not a valid measure for hospital quality comparisons. A
      study was conducted to examine how hospital PSI 90 scores would change if the VTE
      measure were removed from calculation of this composite measure. METHODS: Using
      2014 Medicare inpatient claims data, PSI 90 scores were calculated with and
      without the VTE measure for 3,203 hospitals. Hospital characteristics obtained
      from the American Hospital Association Annual Survey and Centers for Medicare &
      Medicaid Services Payment Update Impact File were merged with PSI 90 scores.
      RESULTS: Removing the VTE outcome measure from the calculation of PSI 90 version
      5.0 improved PSI 90 scores for 17.1% of hospitals but lowered scores for 20.8% of
      hospitals, while 62.1 % had no change in scores. Hospitals were more likely to
      improve on PSI 90 when the VTE measure was removed if they were larger (odds
      ratio [OR] = 1.60; 95% confidence interval [CI] = 1.00-2.58), were major teaching
      hospitals (OR = 1.76; 95% CI = 1.10-2.79), had greater technological resources
      (OR = 2.03; 95% CI = 1.40-2.94), or cared for sicker patients (OR = 1.12; 95% CI
      = 1.01-1.25). CONCLUSION: Inclusion of the surveillance bias-prone VTE outcome
      measure in the PSI 90 composite disproportionately penalizes larger, academic
      hospitals and those that care for sicker patients. Removal of the VTE outcome
      measure from PSI 90 should be strongly considered.

PMID- 30292466
TI  - Soft-tissue vascular malformations and tumors. Part 2: low-flow lesions.
AB  - Vascular malformations and tumors, also known as "vascular anomalies", comprise
      an extensive variety of lesions involving all parts of the body. Due to a lack of
      a complete understanding of the origin and histopathology of such lesions, this
      field has been traditionally obscured by the use of an unclear nomenclature.
      Knowledge of the classification and clinical and imaging characteristics of this
      group of lesions is paramount when managing these patients. The objective of this
      series of two articles is to review the current classification of vascular
      anomalies, to describe the role of imaging in their diagnosis, to summarize their
      distinctive histopathologic, clinical and imaging features, and to discuss the
      treatment options. High-flow lesions were discussed in the first article of this
      series. In this second article, we will focus on low-flow lesions, including
      complex syndromes with associated low-flow malformations.

PMID- 30292467
TI  - Soft-tissue vascular malformations and tumors. Part 1: classification, role of
      imaging and high-flow lesions.
AB  - Vascular malformations and tumors, also known as "vascular anomalies", comprise
      an extensive variety of lesions involving all parts of the body. Knowledge of
      their classification and imaging characteristics is paramount. Whereas
      hemangiomas are benign vascular tumors, characterized by cellular proliferation
      and hyperplasia; vascular malformations are not real tumors and
      characteristically exhibit normal endothelial turnover. Vascular malformations
      are classified according to the predominant vascular channel as arterial,
      capillary, venous, lymphatic, or mixed. Ultrasound and MRI are the main imaging
      modalities used in the diagnosis and classification of the vascular anomalies. In
      this series of two articles we review the classification of vascular anomalies,
      describe the role of imaging, summarize their distinctive histopathogenic,
      clinical and imaging features, and discuss the treatment options. On the first
      article we discuss the high-flow lesions, whereas the slow-flow lesions will be
      reviewed on the second. Complex syndromes with associated vascular tumors and
      malformations will be also presented.

PMID- 30292468
TI  - Metabolic effects of cardiovascular medication: Does it matter?

PMID- 30292469
TI  - Wanted: MicroRNAs to the aid of the diabetic foot.

PMID- 30292470
TI  - Atherosclerosis and immunity: A perspective.
AB  - Atherosclerosis is an inflammatory and multifaceted disorder resulting from the
      accumulation of lipid droplets and several types of immune cells, including
      macrophages, T and B lymphocytes in the arterial walls. A wide variety of
      macrophage subtypes with different functions is implicated in the development and
      progression of atherosclerotic lesions. The prevalence of specific macrophage
      subtypes, which is influenced by cytokines, mediators, and substances composing
      atherosclerotic lesions, has been suggested to be an appropriate indicator of
      transition from a stable to an unstable plaque phenotype. Thus, a better
      understanding of the mechanisms underlying the differentiation of macrophage
      subpopulations in relation to the plaque phenotype would help to develop novel
      approaches aiming at slowing-down the progression of atherosclerotic disease by
      modulating the polarization of these cells. In addition, many arms of the
      adaptative immune system, which are regulated by different subtypes of T and B
      lymphocytes, are involved in atherosclerosis progression and there is an
      increasing effort to identify immune-modulating therapies targeting either T or B
      cells with a potential anti-atherosclerotic impact. This paper summarizes the
      pathophysiology of atherosclerotic disease as it relates to the contribution from
      the immune system, reviewing the crucial role of macrophages, T and B
      lymphocytes.

PMID- 30292471
TI  - Twofold technique of nonappositional repair with single-pass four-throw
      pupilloplasty for iridodialysis.
AB  - The twofold technique of nonappositional closure of iris defect combined with
      single-pass four-throw (SFT) pupilloplasty allows adequate closure of defects in
      varied degrees of iridodialysis, thereby preventing iatrogenically induced
      problems of glare, photophobia, and eccentric pupil.

PMID- 30292472
TI  - Cardiotoxicity after Vemurafenib Administration.

PMID- 30292473
TI  - Simultaneous Implantation of MitraClip Devices in a Patient with Severe Mitral
      and Tricuspid Valve Regurgitation.

PMID- 30292474
TI  - Intravascular papillary endothelial hyperplasia along the intrinsic muscle after
      hand contusion injury: Report of two cases.
AB  - Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson's
      tumor or vegetant intravascular hemangioendothelioma, is a reactive condition
      representing an exuberant organization and recanalization of a thrombus. It can
      occur in normal blood vessels or in vascular malformations, perhaps in response
      to blood vessel injury or thrombosis. In this report, we present the diagnostic
      and therapeutic courses of a 55 year-old woman and an 18 year-old man, who had a
      progressive protruding hand mass following a hand contusion. The pathological
      examination confirmed the diagnosis of IPEH in both patients.

PMID- 30292475
TI  - Association between diet and measures of arterial stiffness in type 1 diabetes -
      Focus on dietary patterns and macronutrient substitutions.
AB  - BACKGROUND AND AIMS: Increased arterial stiffness contributes to diabetic
      vascular complications. We identified dietary factors related to arterial
      stiffness in individuals with type 1 diabetes, a population with high risk of
      cardiovascular disease. METHODS AND RESULTS: Altogether, 612 participants (40%
      men, mean +/- standard deviation age 45 +/- 13 years) completed a validated diet
      questionnaire and underwent measurements of arterial stiffness. Of these, 470
      additionally completed a food record. Exploratory factor analysis was applied to
      identify dietary patterns from the diet questionnaires, and nutrient intakes were
      calculated from food record entries. Arterial stiffness was measured by
      applanation tonometry. Of the seven dietary factors formed, the factor scores of
      "Full-fat cheese and eggs" and "Sweet" patterns were negatively associated with
      measures of arterial stiffness. In the multivariable macronutrient substitution
      models, favouring carbohydrates over fats was associated with higher aortic mean
      arterial pressure and aortic pulse wave velocity. When carbohydrates were
      consumed in place of proteins, higher aortic pulse pressure, aortic mean arterial
      pressure, and augmentation index were recorded. Replacing energy from alcohol
      with proteins, was associated with lower aortic pulse pressure, aortic mean
      arterial pressure, and augmentation index. Relative distributions of dietary
      fatty acids were neutral with respect to the measures of arterial stiffness.
      CONCLUSION: The macronutrient distribution of the diet is likely to affect the
      resilience of the arteries. Our observations suggest that reducing energy intake
      from carbohydrates and alcohol may be beneficial. These observations, especially
      those dealing with dietary patterns, need to be confirmed in a longitudinal
      study.

PMID- 30292476
TI  - Incidence of grade 3-4 liver injury under immune checkpoints inhibitors: A
      retrospective study.

PMID- 30292477
TI  - Characterization of receptor binding kinetics for vascular endothelial growth
      factor-A using SPR.
AB  - Angiogenesis is a highly regulated process orchestrated, in large part, by the
      vascular endothelial growth factor-A (VEGF-A) system of ligands and receptors.
      Considerable effort has been invested in finding optimal ways to modulate VEGF-A
      activity to treat disease, however, the mechanisms by which the various
      components interact remain poorly understood. This is in part because of the
      difficulty of analyzing the various interactions in an intercomparable manner. In
      the present study, we established conditions to allow for the detailed
      characterization of the molecular interactions between VEGF and its receptors and
      the co-receptor NRP-1 using surface plasmon resonance (SPR). We found that VEGF
      dissociated 25-times faster from its major signaling receptor, VEGF receptor-2
      (VEGFR-2) than from its "decoy" receptor, VEGF receptor-1 (VEGFR-1). Using a
      systematic approach, we obtained kinetic parameters for each individual
      interaction under a consistent set of experimental conditions allowing for
      comparison between various receptors. The set of quantitative kinetic parameters
      and experimental conditions reported herein will provide valuable tools for
      developing comprehensive models of the VEGF system.

PMID- 30292478
TI  - Epidemiology of common resistant bacterial pathogens in the countries of the Arab
      League.
AB  - No uniformly organised collection of data regarding antimicrobial resistance has
      occurred in the countries of the Arab League. 19 countries of the Arab League
      have published data for antimicrobial susceptibility for the WHO priority
      organisms, and seven of 14 of these organisms are included in this Review
      (Escherichia coli, Klebsiella spp, Pseudomonas aeruginosa, Acinetobacter
      baumannii, Salmonella spp, Staphylococcus aureus, and Streptococcus pneumoniae).
      Although E coli and Klebsiella spp resistance to third-generation cephalosporins
      is common in all countries, with prevalence reaching more than 50% in Egypt and
      Syria, carbapenem resistance is emerging, albeit with a prevalence of less than
      10%. Conversely, a large amount of carbapenem resistance has been reported for P
      aeruginosa and A baumannii across the Arab League, reaching 50% and 88% of
      isolates in some countries. As for Salmonella spp, the prevalence of
      fluoroquinolone resistance has exceeded 30% in several areas. With regards to the
      Gram-positive pathogens, the prevalence of meticillin resistance in S aureus is
      reported to be between 20% and 30% in most countries, but exceeds 60% in Egypt
      and Iraq. The prevalence of penicillin non-susceptibility among pneumococci has
      reached more than 20% in Algeria, Egypt, Morocco, Saudi Arabia, and Tunisia.
      These findings highlight the need for structured national plans in the region to
      target infection prevention and antimicrobial stewardship.

PMID- 30292479
TI  - Phage therapy 2.0: where do we stand?

PMID- 30292480
TI  - Antimicrobial resistance following mass azithromycin distribution for trachoma: a
      systematic review.
AB  - Mass azithromycin distribution is a core component of trachoma control programmes
      and could reduce mortality in children younger than 5 years in some settings. In
      this systematic review we synthesise evidence on the emergence of antimicrobial
      resistance after mass azithromycin distribution. We searched electronic databases
      for publications up to June 14, 2018. We included studies of any type (excluding
      modelling studies, surveillance reports, and review articles) on community-wide
      distribution of oral azithromycin for the prevention and treatment of trachoma
      that assessed macrolide resistance, without restrictions to the type of organism.
      We extracted prevalence of resistance from published reports and requested
      unpublished data from authors of included studies. Of 213 identified studies, 19
      met inclusion criteria (12 assessed Streptococcus pneumoniae) and were used for
      qualitative synthesis. Macrolide resistance after azithromycin distribution was
      reported in three of the five organisms studied. The lack of resistance in
      Chlamydia trachomatis suggests that azithromycin might remain effective for
      trachoma programmes, but evidence is scarce. As mass azithromycin distribution
      for trachoma continues and is considered for other indications, ongoing
      monitoring of antimicrobial resistance will be required.

PMID- 30292481
TI  - Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds
      infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double
      blind phase 1/2 trial.
AB  - BACKGROUND: Wound infections are the main cause of sepsis in patients with burns
      and increase burn-related morbidity and mortality. Bacteriophages, natural
      bacterial viruses, are being considered as an alternative therapy to treat
      infections caused by multidrug-resistant bacteria. We aimed to compare the
      efficacy and tolerability of a cocktail of lytic anti-Pseudomonas aeruginosa
      bacteriophages with standard of care for patients with burns. METHODS: In this
      randomised phase 1/2 trial, patients with a confirmed burn wound infection were
      recruited from nine burn centres in hospitals in France and Belgium. Patients
      were eligible if they were aged 18 years or older and had a burn wound clinically
      infected with P aeruginosa. Eligible participants were randomly assigned (1:1) by
      use of an interactive web response system to a cocktail of 12 natural lytic anti
      P aeruginosa bacteriophages (PP1131; 1 * 106 plaque-forming units [PFU] per mL)
      or standard of care (1% sulfadiazine silver emulsion cream), both given as a
      daily topical treatment for 7 days, with 14 days of follow-up. Masking of
      treatment from clinicians was not possible because of the appearance of the two
      treatments (standard of care a thick cream, PP1131 a clear liquid applied via a
      dressing), but assignments were masked from microbiologists who analysed the
      samples and patients (treatment applied while patients were under general
      anaesthetic). The primary endpoint was median time to sustained reduction in
      bacterial burden by at least two quadrants via a four-quadrant method, assessed
      by use of daily swabs in all participants with a microbiologically documented
      infection at day 0 who were given at least one sulfadiazine silver or phage
      dressing (modified intention-to-treat population). Safety was assessed in all
      participants who received at least one dressing according to protocol. Ancillary
      studies were done in the per-protocol population (all PP1131 participants who
      completed 7 days of treatment) to assess the reasons for success or failure of
      phage therapy. This trial is registered with the European Clinical Trials
      database, number 2014-000714-65, and ClinicalTrials.gov, number NCT02116010, and
      is now closed. FINDINGS: Between July 22, 2015, and Jan 2, 2017, across two
      recruitment periods spanning 13 months, 27 patients were recruited and randomly
      assigned to receive phage therapy (n=13) or standard of care (n=14). One patient
      in the standard of care group was not exposed to treatment, giving a safety
      population of 26 patients (PP1131 n=13, standard of care n=13), and one patient
      in the PP1131 group did not have an infection at day 0, giving an efficacy
      population of 25 patients (PP1131 n=12, standard of care n=13). The trial was
      stopped on Jan 2, 2017, because of the insufficient efficacy of PP1131. The
      primary endpoint was reached in a median of 144 h (95% CI 48-not reached) in the
      PP1131 group versus a median of 47 h (23-122) in the standard of care group
      (hazard ratio 0.29, 95% CI 0.10-0.79; p=0.018). In the PP1131 group, six (50%) of
      12 analysable participants had a maximal bacterial burden versus two (15%) of 13
      in the standard of care group. PP1131 titre decreased after manufacturing and
      participants were given a lower concentration of phages than expected (1 * 102
      PFU/mL per daily dose). In the PP1131 group, three (23%) of 13 analysable
      participants had adverse events versus seven (54%) of 13 in the standard of care
      group. One participant in each group died after follow-up and the deaths were
      determined to not be related to treatment. The ancillary study showed that the
      bacteria isolated from patients with failed PP1131 treatment were resistant to
      low phage doses. INTERPRETATION: At very low concentrations, PP1131 decreased
      bacterial burden in burn wounds at a slower pace than standard of care. Further
      studies using increased phage concentrations and phagograms in a larger sample of
      participants are warranted. FUNDING: European Commission: Framework Programme 7.

PMID- 30292482
TI  - Clinical outcomes of home parenteral nutrition patients using taurolidine as
      catheter lock: A long-term cohort study.
AB  - BACKGROUND & AIMS: Central venous access device (CVAD)-related complications,
      such as central-line associated bloodstream infections (CLABSIs), CVAD-related
      venous thromboses (CRVTs) and -occlusions frequently occur in home parenteral
      nutrition (HPN) patients. A preventive strategy to decrease the incidence of
      CLABSIs is the use of CVAD lock solutions, such as 2% taurolidine. The aim of
      this study was to evaluate long-term clinical outcomes of our HPN cohort while
      using taurolidine as lock solution. In addition, we explored risk factors
      associated with CVAD-related complications. METHODS: We conducted a retrospective
      analysis of complications (CLABSIs, CRVTs and CVAD occlusions) and adverse events
      in adult HPN patients while using taurolidine as lock solution. Patients with a
      benign underlying disease leading to intestinal failure were included between
      2006 and 2017 at our tertiary referral centre for intestinal failure. Primary
      outcome was the effectiveness of taurolidine, as described by complication
      incidence rates. Secondary objectives were to assess adverse events of
      taurolidine, complication rates of patients who subsequently discontinued
      taurolidine and started using 0.9% saline alternatively, and risk factors
      associated with complications. RESULTS: In total, 270 HPN patients used
      taurolidine during 338521 catheter days. CLABSIs, CRVTs and CVAD occlusions
      occurred at a rate of 0.60 (CI95% 0.52-0.69), 0.28 (CI95% 0.23-0.34), and 0.12
      (CI95% 0.08-0.16) events per 1000 catheter days, respectively. In 24 (9%)
      patients, mild to moderate adverse events resulted in discontinuation of 2%
      taurolidine. A subsequent switch to 0.9% saline resulted in an increased CLABSI
      rate (adjusted rate ratio 4.01 (95%CI 1.23-13.04), P = 0.02). Several risk
      factors were identified for CLABSIs (a lower age, nontunneled catheters, infusion
      frequency), CRVTs (site of vein insertion), and CVAD occlusions (type of CVAD).
      CONCLUSION: Complication rates remained low in the long-term, and use of
      taurolidine was generally safe. The identified risk factors may help to create
      new strategies to further prevent CVAD-related complications and improve HPN care
      in the future.

PMID- 30292483
TI  - Resting energy expenditure equations in amyotrophic lateral sclerosis, creation
      of an ALS-specific equation.
AB  - INTRODUCTION: Resting energy expenditure (REE) formulas for healthy people (HP)
      are used to calculate REE (cREE) in amyotrophic lateral sclerosis (ALS) patients.
      In 50-60% of ALS cases an increase of measured REE (mREE) in indirect calometry
      (IC) compared to cREE is found. The aims here were (i) to assess the accuracy of
      cREE assessed using 11 formulas as compared to mREE and (ii) to create (if
      necessary) a specific cREE formula for ALS patients. METHOD: 315 Patients
      followed in the ALS expert center of Limoges between 1996 and 2014 were included.
      mREE assessed with IC and cREE calculated with 11 predictive formulas (Harris
      Benedict (HB) 1919, HB 1984, WSchofield, De Lorenzo, Johnstone, Mifflin, WHO/FAO,
      Owen, Fleisch, Wang and Rosenbaum) were determined at the time of diagnosis. Fat
      free mass (FFM) and fat mass (FM) were measured with impedancemetry. A Bland and
      Altman analysis was carried out. The percentage of accurate prediction +/-10% of
      mREE, and intraclass correlation coefficients (ICC) were calculated. Using a
      derivation sample, a new REE formula was created using multiple linear regression
      according to sex, age, FFM and FM. Accuracy of this formula was assessed in a
      validation sample. RESULTS: ICC ranged between 0.60 and 0.71 (moderate
      agreement), and percentage of accurate prediction between 27.3% and 57.5%.
      Underestimation was found from 31.7% to 71.4% of cases. According to these
      unsatisfactory results we created an ALS-specific formula in a derivation sample
      (130 patients). ICC and percentage of accurate prediction increased in a
      validation sample (143 patients) to 0.85 (very good agreement) and 65.0%
      respectively, with 17.5% underestimation. CONCLUSION: REE formulas for HP
      underestimate REE in ALS patients compared to mREE. Our new ALS-specific formula
      produced better results than formulas for HP. This formula can be used to
      estimate REE in ALS patients if IC is not accessible.

PMID- 30292484
TI  - Anaesthetic strategy during endovascular therapy.

PMID- 30292485
TI  - Cranial nerves VII and XII palsy after shoulder surgery.
AB  - A 46-year-old man underwent a left shoulder surgery in the beach chair position
      with general anaesthesia and oro-tracheal intubation preceded by a left
      interscalenic block. Patient's head was attached to the headrest in a position of
      soft extension and moderate right rotation with adhesive tape surrounding his
      forehead and mandible. Surgery was marked by repeated vertical tractions on the
      left arm and by blood resorption of the arthroscopy's irrigation fluid, including
      epinephrine, which translated in a heart rate and arterial blood pressure rise.
      Upon waking the patient had severe headaches, left Horner's sign, left facial
      paresis and a left lingual paralysis. MRI and CT scan did not show any carotid
      dissection or parapharyngeal lesion. Electromyogram and neurological examination
      confirmed a VII and XII cranial nerve peripheral lesion, which took several
      months to regress. An ischaemic complication was suspected although the most
      probable cause of the patient's symptoms was subsequent to an Eagle's syndrome
      neurapraxia related to a long styloid process.

PMID- 30292486
TI  - Increased middle cerebral artery Doppler velocities after stroke thrombectomy
      performed under general anaesthesia: A pilot monocentric retrospective study.

PMID- 30292487
TI  - Prolonged continuous wound infiltration with a local anaesthetic after total
      mastectomy: pharmacokinetics and preliminary results on postoperative pain.

PMID- 30292488
TI  - Serious adverse events and deaths linked to poor ventilator use: A report of four
      closed claims.
AB  - Through this series of four closed claims, we highlight examples of accidents
      stemming from poor ventilator use. We then review the main issues in this regard
      as reported in the literature and by learned societies. This case series has led
      us to emphasise the need for safety procedures involving systematic checks prior
      to use, declaration and analysis of the risk, as well as feedback and teaching
      regarding ventilation systems.

PMID- 30292489
TI  - The impact of lipids, lipid oxidation, and inflammation on AMD, and the potential
      role of miRNAs on lipid metabolism in the RPE.
AB  - The accumulation of lipids within drusen, the epidemiologic link of a high fat
      diet, and the identification of polymorphisms in genes involved in lipid
      metabolism that are associated with disease risk, have prompted interest in the
      role of lipid abnormalities in AMD. Despite intensive investigation, our
      understanding of how lipid abnormalities contribute to AMD development remains
      unclear. Lipid metabolism is tightly regulated, and its dysregulation can trigger
      excess lipid accumulation within the RPE and Bruch's membrane. The high oxidative
      stress environment of the macula can promote lipid oxidation, impairing their
      original function as well as producing oxidation-specific epitopes (OSE), which
      unless neutralized, can induce unwanted inflammation that additionally
      contributes to AMD progression. Considering the multiple layers of lipid
      metabolism and inflammation, and the ability to simultaneously target multiple
      pathways, microRNA (miRNAs) have emerged as important regulators of many age
      related diseases including atherosclerosis and Alzheimer's disease. These
      diseases have similar etiologic characteristics such as lipid-rich deposits,
      oxidative stress, and inflammation with AMD, which suggests that miRNAs might
      influence lipid metabolism in AMD. In this review, we discuss the contribution of
      lipids to AMD pathobiology and introduce how miRNAs might affect lipid metabolism
      during lesion development. Establishing how miRNAs contribute to lipid
      accumulation in AMD will help to define the role of lipids in AMD, and open new
      treatment avenues for this enigmatic disease.

PMID- 30292490
TI  - Expression of retinoic acid signaling components ADH7 and ALDH1A1 is reduced in
      aniridia limbal epithelial cells and a siRNA primary cell based aniridia model.
AB  - PAX6-related Aniridia is a sight-threatening disease involving progression of
      secondary glaucoma and aniridia related keratopathy (ARK). Change or loss of
      limbal epithelial progenitors causes epithelial surface defects. We analyzed the
      effect of PAX6 on mRNA expression changes with a two-step approach, as follows.
      First, we sequenced mRNA from limbal epithelial cells isolated from controls and
      aniridia patients. Second, we confirmed the bioinformatics and literature-based
      result list for a small interfering RNA (siRNA)-based primary aniridia cell model
      (PAX6 knockdown). With this approach, we expected that the genes directly
      influenced by PAX6 would be distinguishable from those affected secondarily by
      the ARK disease state. Therefore, epithelial cells were isolated from the limbus
      region of two patients with aniridia and cultured in keratinocyte serum-free
      medium. Normal control cells were obtained from the limbus region of corneal
      donors. For the siRNA-based aniridia cell model, cells were transfected with
      Lipofectamine and 5 nM siRNA against PAX6 or control treatment. All cells were
      lysed to yield DNA, RNA, and protein. Reduction of PAX6 protein was assessed by
      western blot. Aniridia and control Poly-A-enriched RNA libraries were subjected
      to next-generation sequencing. The differential analysis was a combination of
      quantification with RSEM and differential tests with edgeR. Gene lists were
      filtered by comparison to NCBI GEO datasets, annotated with DAVID, and manually
      annotated using a literature search. Based on the resulting filtered gene list,
      qPCR primers were purchased, and candidate genes (TP63, ABCG2, ADH7, ALDH1A1,
      PITX1, DKK1, DSG1, KRT12, KRT3, KRT13, SPINK6, SPINK7, CTSV, SERPINB1) were
      verified by qPCR on the siRNA-based aniridia cell model. We identified genes that
      might be regulated by PAX6 and showed that SPINK7 mRNA, which codes for a
      protease inhibitor, is downregulated in patients as well as in our primary
      aniridia cell model. ALDH1A1 and AHD7 mRNA levels were reduced in limbal
      epithelial cells of aniridia patients, and both transcripts were downregulated by
      PAX6 knockdown in our cell model. This siRNA-based aniridia cell model is a
      valuable tool for confirming identified PAX6-affected genes that might promote
      ARK pathogenesis. The model recapitulated expression changes for SPINK7, ADH7,
      and ALDH1A1 that were also observed in patient samples. These results provide
      evidence that PAX6 might drive corneal epithelial differentiation by direct or
      indirect control of retinoic acid signaling processes through ADH7 and ALDH1A1.

PMID- 30292491
TI  - Antenatal Detection of Treatable Critical Congenital Heart Disease Is Associated
      with Lower Morbidity and Mortality.
AB  - OBJECTIVE: To establish the impact that timing of diagnosis and place of birth
      have on neonatal outcomes in those with readily treatable critical congenital
      heart disease. STUDY DESIGN: This was a population-based study with a complete
      national cohort of live-born infants with transposition of the great arteries and
      aortic arch obstruction in New Zealand between 2006 and 2014. Timing of
      diagnosis, place of birth, survival to surgery, in-hospital events, and neonatal
      mortality were reviewed. Live births with a gestation of >=35 weeks and without
      associated major extracardiac anomalies were included for analysis. RESULTS: A
      total of 166 live-born infants with transposition of the great arteries and 87
      with aortic arch obstruction were included. Antenatal detection increased from
      32% in the first 3 years to 47% in the last 3 years (P = .05). During the same
      period, neonatal mortality decreased from 9% to 1% (P = .02). No deaths occurred
      after surgical intervention. An antenatal diagnosis was associated with decreased
      mortality (1/97 [1%] vs 11/156 [7%]; P = .03) and birth outside the surgical
      center was associated with increased risk of mortality (11/147 [7%] vs 1/106
      [1%]; P = .02). Those with an antenatal diagnosis required fewer hours of
      mechanical ventilation (P = .02) and had shorter durations of hospital stay (P =
      .05) compared with those diagnosed >48 hours after birth. CONCLUSIONS: The
      mortality risk for transposition of the great arteries and critical aortic arch
      obstruction is greatest before cardiac surgery. Improved antenatal detection
      allowing delivery at a surgical center is associated with reduced mortality.

PMID- 30292493
TI  - Fentanyl test strips as an opioid overdose prevention strategy: Findings from a
      syringe services program in the Southeastern United States.
AB  - BACKGROUND: In 2016, the number of overdose deaths involving illicitly
      manufactured fentanyl (IMF) surpassed heroin and prescription opioid deaths in
      the United States for the first time, with IMF-involved overdose deaths
      increasing more than 500% across 10 states from 2013 to 2016. IMF is an extremely
      potent synthetic opioid that is regularly mixed with heroin and often sold to
      unwitting consumers. Community-based organizations have started to distribute
      fentanyl test strips (FTS) as a strategy to identify IMF in street purchased
      products. We investigated the association between FTS use and changes in drug use
      behavior and perceived overdose safety among a community-based sample of people
      who inject drugs (PWID) in the United States. METHODS: Between September-October
      2017, a total of 125 PWID completed an online survey about their most recent FTS
      use in Greensboro, North Carolina. Our first outcome of interest included whether
      PWID engaged in any of the following changes in drug use behavior after using
      FTS: used less than usual, administered tester shot, pushed syringe plunger
      slower than usual, and snorted instead of injected. Our second outcome of
      interest was whether PWID felt that FTS use made them feel better able to protect
      themselves from overdose. We conducted bivariate and multivariate analyses to
      determine the association between FTS use and these two outcomes. RESULTS:
      Overall, 63% of the sample reported a positive FTS test result and 81% reported
      using FTS prior to consuming their drugs. For the outcomes, 43% reported a change
      in drug use behavior and 77% indicated increased perceived overdose safety by
      using FTS. In multivariable models adjusting for demographic and FTS correlates,
      PWID with a positive FTS test result had five times the odds of reporting changes
      in drug use behavior compared to those with a negative result. PWID who used the
      FTS after drug consumption were 70% less likely to report behavioral changes at
      subsequent drug consumption compared to those who used it before consumption.
      PWID who were not existing clients of the syringe services program had four times
      higher odds than existing clients to report increased overdose safety from using
      FTS. CONCLUSIONS: We found that using FTS and receiving a positive test result
      was associated with changes in drug use behavior and perceptions of overdose
      safety. FTS may represent an effective addition to current overdose prevention
      efforts when included with other evidence-based strategies to prevent opioid
      overdose and related harm.

PMID- 30292494
TI  - National survey of fiducial marker insertion for prostate image guided
      radiotherapy.
AB  - INTRODUCTION: In the United Kingdom fiducial marker IGRT is the second most
      common verification method employed in radical prostate radiotherapy yet little
      evidence exists to support centres introducing or developing this practice. We
      developed a survey to elicit current fiducial marker practices adopted in the UK,
      to recommend standardisation of practice. METHODS: A 16 question survey was
      distributed across UK Radiotherapy centres via promotion at the British Uro
      Oncology Group Conference, 2016. Included were questions relating to workforce
      planning, patient preparation, insertion procedure and verification methods. The
      survey was open from September 2016 to January 2017. RESULTS: Results from 15
      centres routinely inserting fiducial markers for prostate IGRT are presented.
      Eleven professional groups insert fiducial markers across the UK. Fourteen
      centres insert fiducial markers trans-rectally; one trans-perineally. Centres
      adopting a trans-rectal approach administer prophylactic ciprofloxacin as a
      single agent or combined with gentamicin or metronidazole; poor agreement between
      regimes presented. One centre has introduced targeted antibiotic prophylaxis.
      Five brands of fiducial markers are utilised nationally. Fourteen centres
      standardly insert three single fiducial markers, two common configurations
      emerged. Coupled fiducial markers are routinely implanted by one centre. All
      centres delay at least one week between fiducial marker insertion and planning
      CT; seven centres wait two weeks. The most common fiducial verification method is
      two-dimensional, paired kilo Voltage imaging. CONCLUSION: Variation in fiducial
      marker practice across the UK is considerable. Standardisation is required to
      support centres and healthcare professionals developing this service. Seven
      recommendations, to unify practice, have been proposed based on survey results
      and literature.

PMID- 30292495
TI  - Magnetic Resonance Imaging of synovitis in knees of patients with osteoarthritis
      without injected contrast agents using T1 quantification.
AB  - INTRODUCTION: To measure the range of T1 values of synovitis using three Tesla (3
      T) magnetic resonance imaging (MRI) in patients with osteoarthritis to assess the
      potential of T1 mapping for identifying synovitis from other features in the knee
      on unenhanced magnetic resonance scans. METHODS: After receiving institutional
      ethical approval, 83 patients who met the American College of Rheumatology
      criteria for diagnosis of osteoarthritis of the knee were scanned using a 3 T
      Magnetic Resonance Imaging scanner. T1 maps were calculated from spoiled gradient
      echo images acquired with five different flip angles of 5 degrees -25 degrees .
      Mean values for the T1 measurements were calculated and compared to existing data
      from the published literature for anatomical and pathological structures of the
      knee. RESULTS: T1 values recorded in patients suffering from osteoarthritis
      demonstrated that T1 values for synovitis (confirmed on gadolinium enhanced
      images) fall in a narrow range (849-1277 ms, mean 1005 ms SD 91) delineating this
      from other structures of the knee such as muscle (T1 value range 1305-2638 ms,
      mean 1785 ms SD 304) and synovial fluid (T1 value range 3867-4129 ms, mean 3915
      SD 899) at 3 T. CONCLUSION: T1 values measured in synovitis in patients with
      osteoarthritis of the knee demonstrated a range of values distinct to those
      measured in muscle and synovial fluid at 3 T. This offers potential for the use
      of T1 maps to delineate or quantify synovitis in patients who are unwilling or
      unable to receive injectable contrast agents.

PMID- 30292496
TI  - Embedding consultant radiographer roles within radiology departments: A framework
      for success.
AB  - INTRODUCTION: Many organisations struggle to clearly differentiate the
      radiographer consultant role from advanced or specialist practice, with newly
      appointed consultant practitioners often ill-prepared for working at this level.
      This article discusses the design, implementation and validation of an outcomes
      framework for benchmarking competencies for trainee or new-in-post consultant
      radiographers. METHODS: Five experienced radiographers from different clinical
      specialisms were seconded to a twelve month consultant trainee post, guided by a
      locally-devised outcomes framework. A longitudinal qualitative study explored,
      from the radiographers' perspective, the impact of the outcomes framework on the
      transition to consultant practice and beyond. Data collection included semi
      structured interviews (months 1, 6 and 12), validation via a focus group (month
      18) and a group interview (5 years). RESULTS: Early interactions with framework
      objectives were mechanistic, but as participants better understood the role more
      creative approaches emerged. Despite diverse clinical expertise, the framework
      facilitated parity between participants, promoting transparency and credibility
      which was important in how the consultant role was perceived. All participants
      achieved all framework outcomes and were subsequently appointed to substantive
      consultant radiographer positions. CONCLUSION: This outcomes framework
      facilitates experienced radiographers to successfully transition into consultant
      radiographers, enabling them to meet multiple non-clinical targets while
      continuing to work effectively within a changing clinical environment. It is the
      first validated benchmarking tool designed to support the transition to
      radiographer consultant practice. Adoption of the tool will provide a
      standardised measure of consultant radiographer outcomes that will promote inter
      organisational transferability hitherto unseen in the UK.

PMID- 30292497
TI  - TRUFU: Therapeutic radiographer undertaking follow up for prostate cancer
      patients.
AB  - INTRODUCTION: A study was proposed to examine the impact to patients and the
      Oncology review team, of extending the role of the Therapeutic Radiographer to
      undertake follow up review of prostate cancer patients who have completed a
      radical course of external beam radiotherapy treatment. METHOD: A total of 30
      patients attending for routine radiotherapy follow up were included in an
      observational study. Patients were assigned for review with a Doctor or a
      Therapeutic Radiographer using 1:1 randomisation and a number of time points were
      recorded and analysed. RESULTS: Of the 44 patients screened, 30 patients were
      recruited. Average time from scheduled appointment time to departure from clinic
      was 36 min for both the doctor and Therapeutic Radiographer. The average length
      of Consultation was 19 min for the Therapeutic Radiographer and 10 min for the
      Doctor. Average length of wait for patients from scheduled appointment time to
      being taken for review was 17 min for the Therapeutic Radiographer and 25 min for
      the Doctor. Of the patients who completed questionnaires, 23/28 had no preference
      of reviewer, 2/28 declared a preference to be seen by a doctor, whilst 3/28
      stated a preference for review with a Therapeutic Radiographer. CONCLUSION: The
      results of the study are encouraging and should be further investigated in an
      attempt of developing what would be a very rewarding aspect of the Therapeutic
      Radiographers role.

PMID- 30292498
TI  - Running water sound technique in contrast-based voiding cystourethrogram: A case
      control study.
AB  - BACKGROUND: An intervention that can reduce the patient void time during a
      voiding cystourethrogram (VCUG) procedure can reduce the total radiation dose to
      the patient. This is because a delay in voiding leads to a high number of
      intermittent screenings to monitor if voiding occurs. This study assessed the
      impact of running-water sound (RWS) upon patients' voiding parameters and
      fluoroscopy screening times during VCUG examinations among children and adults.
      MATERIALS AND METHODS: A case-control study involving 252 patients was undertaken
      which consisted two groups (control and test) of adults and children. The test
      groups underwent VCUG with RWS technique while the control groups underwent the
      procedure normally. T-test was used to compare the study parameters between the
      two groups and a p-value less than 0.05 was interpreted as significant. RESULTS:
      The mean screening times (s) for children who underwent VCUG with and without RWS
      were 17.15 +/- 2.5s and 30.61 +/- 5.1s respectively (p = 0.0024). For adults, the
      RWS technique recorded a mean screening time of 37.36 +/- 4.4s while the non-RWS
      procedures recorded 49.80 +/- 5.2s (p = 0.001). The participants who received RWS
      intervention also felt the urge to void earlier than those who received no RWS
      intervention. The differences were also statistically significant for both
      children and adults. CONCLUSION: The study being one of the first in this subject
      area indicates that the application of RWS technique induces early urge of
      iodinated-contrast voiding, and reduces voiding and fluoroscopy screening times
      during VCUG among children and adults. This simple technique can potentially
      enhance current practice.

PMID- 30292499
TI  - Breast compression techniques in screening mammography - A Maltese evaluation
      project.
AB  - INTRODUCTION: In screening mammography, the radiographer should be responsible
      for providing mammograms of high diagnostic value, possibly without subjecting
      clients to a painful experience. This skill is demonstrated via the technique of
      breast compression and is explored in this study by analysing insights about
      methods and underlying principles in regards to this procedure. METHODS: One-to
      one semi-structured interviews were conducted with radiographers who perform
      screening mammography in Malta. For data analysis, a descriptive phenomenological
      approach following a simplified version of Hycner's (1985) method was adopted.
      RESULTS: Five general themes were extracted from the data; meeting the client,
      preparing the client, the mammography procedure, pain from compression and client
      turnout. It was determined that the participants alter their breast compression
      technique according to the client rather than following a rigid step-by-step
      process and that explanation and requesting client feedback are essential to
      obtain cooperation. Additionally, mammography positioning and compression
      application are tailored in a way that encourage compliance, however not at the
      expense of degrading image quality. Ultimately, it is also believed that a proper
      breast compression technique positively influences client turnout. CONCLUSION:
      The results of this study demonstrate that radiographers should be flexible in
      their approach in order to carry out a successful breast compression technique.
      However, it has also been shown that such effectiveness in practice is gained
      from experience rather than initial training. If exposed to this study's
      findings, new mammographers would be able to form a robust core of knowledge
      before embarking on the challenging specialisation of mammography.

PMID- 30292500
TI  - An evaluation of online information available for women with breast implants aged
      47-73 who have been invited to attend the NHS Breast Screening Programme.
AB  - INTRODUCTION: The Internet has become an innovative instrument older adults
      utilise to obtain health-related information. Poor quality health information may
      cause harm to individuals. If not accessible, or at a level comprehended by
      target audiences, this does not support the development of their knowledge and
      subsequently hinders patient's ability to make informed-decisions. AIM: evaluate
      quality, readability, accessibility and usability of online information for women
      with breast implants invited to attend the NHSBSP. METHODS: Eight websites were
      evaluated for quality and accessibility/usability using uniquely developed
      evaluation tools. The 'three-click' rule was used to assess usability and SMOG
      tool to measure readability. Quality and accessibility/usability scores were
      combined to give an overall score, which were then converted into percentages. A
      percentage categorisation system ranked the percentage scores from poor to
      excellent. Readability scores were represented in number of years of education
      required to read/understand text. RESULTS: Average quality score = 14 (66.6%).
      Average accessibility/usability score = 9 (56.6%). 7 websites achieved an overall
      score in the poor percentage category (below 75%). Over 50% of websites had
      readability levels higher than the recommended level for online health
      information. 100% were above the UK average reading age. CONCLUSION: Websites
      providing information on breast screening with implants are not easily
      accessible, are of poor quality and too difficult to be read by most people. The
      quality, readability and accessibility of each website's content should be
      improved to help support women make informed decisions relating-to breast
      screening attendance, increase their understanding and lessen their anxiety.

PMID- 30292501
TI  - A questionnaire study of radiography educator opinions about patient lead
      shielding during digital projection radiography.
AB  - BACKGROUND: In projection radiography, lead rubber shielding has long been used
      to protect the gonads both within and outside the collimated field. However, the
      relative radio-sensitivity of the gonads is considered lower than previously, and
      doses from digital projection radiography are reported as being lower than in
      previous eras. These factors, along with technical difficulties encountered in
      placing lead shielding effectively, lead to varied opinions on the efficacy of
      such shielding in peer reviewed literature. This current study has investigated
      what is currently being taught as good practice concerning the use of lead
      shielding during projection radiography. METHOD: An online questionnaire was
      distributed to a purposive sample of 44 radiography educators across 15
      countries, with the aim of establishing radiography educators' opinions about
      patient lead shielding and its teaching. RESULTS: From the 27 responding
      educators, 57% (n = 15) teach students to apply gonadal shielding across a range
      of radiographic examinations; only 22% (n = 6) do the same for the breast,
      despite respondents being aware that the breast has higher relative radio
      sensitivity than the gonads. Radiation protection was the primary reason given
      for using shielding. Students are generally expected to apply patient lead
      shielding during assessments, although a small number of respondents report that
      students must justify whether or not to apply lead shielding. Educators generally
      held the opinion that no matter what they are taught, students are influenced by
      what they see radiographers do in clinical practice. CONCLUSIONS: The current
      study has not found consensus in literature or in radiography educators' opinions
      concerning the use of patient lead shielding. Findings suggest that a large scale
      empirical study to establish a specific evidence base for the appropriate use of
      lead shielding across a range of projection radiography examinations would be
      useful.

PMID- 30292502
TI  - Assessment of isocenter alignment during CT colonography: Implications for
      clinical practice.
AB  - INTRODUCTION: Optimization of image quality and patient radiation dose is
      achieved in part by positioning the patient at the isocenter of the CT gantry.
      The aim of this study was to establish whether there was increased isocenter
      misalignment (IM) in CT colonography (CTC) scans by comparing patient position
      during the prone part of a CTC to patient position during renal stone protocol CT
      (CT-KUB) and patient position during the supine part of a CTC to patient position
      during abdominopelvic CT (CT-AP). METHODS: Two hundred and twenty two consecutive
      outpatient adult CTC studies performed between January and December 2016 were
      retrospectively analyzed. Automated dose-tracking software was used to quantify
      IM in the x and y planes. Renal stone CT-KUB (n = 100) and standard CT-AP (n =
      100) were used as comparison studies. RESULTS: IM during CTC was significantly
      greater in the y-axis compared with the x-axis for both prone (p = 0.002) and
      supine (p < 0.001) scanning. IM was significantly greater during prone CTC
      compared with CT-KUB (p = 0.008) and during supine CTC compared with CT-AP (p =
      0.0001). IM was shown to be slightly greater in studies performed by more
      experienced radiographers (p = 0.04). IM was not associated with patient age,
      gender or size (p > 0.05 for all). CONCLUSION: Isocenter misalignment is greater
      during CT colonography compared with CT-KUB or CT-AP. Strategies for improving
      patient positioning could include radiographer education and automated patient
      centering solutions.

PMID- 30292503
TI  - The detection of wooden foreign bodies: An experimental study comparing direct
      digital radiography (DDR) and ultrasonography.
AB  - INTRODUCTION: This experimental study compares the appropriateness of direct
      digital radiography (DDR) and ultrasonography at detecting soft-tissue wooden
      foreign bodies (FBs) in extremities. METHODS: Varying wooden FB splinters (2 mm,
      5 mm and 10 mm) were inserted into eight porcine feet to simulate a patient
      presenting with a soft-tissue FB injury. Each of the FBs was placed in muscle
      distant, behind and near bone in the porcine feet. Control groups were used to
      check for false-positive diagnoses and, based on the presence of FBs; images were
      given a score depending on the level of visibility by the researcher. RESULTS: A
      higher detection rate was achieved for all FBs in muscle distant from bone using
      ultrasound. All of the 2 mm and 5 mm wooden FBs were not detected using DDR. The
      sensitivity in detecting the FBs was 5.8% and 30% in DDR and ultrasound
      respectively. CONCLUSION: Poor sensitivities and specificities were identified in
      this study. However, this study shows that ultrasound remains superior to DDR at
      identifying small foreign body objects. This study demonstrates that ultrasound
      can be a clinically effective tool for detecting suspected wooden FBs >5 mm in
      the foot and thus should be considered as the primary imaging modality of choice
      for referring clinicians.

PMID- 30292504
TI  - A phantom study of the performance of model-based iterative reconstruction in low
      dose chest and abdominal CT: When are benefits maximized?
AB  - INTRODUCTION: The aim of this study was to assess and compare the effects of CT
      image reconstruction techniques on low-dose CT image quality using phantoms.
      METHODS: Anthropomorphic torso and spatial/contrast-resolution phantoms were
      scanned at decreasing tube currents between 400 and 10 mA. CT thorax and
      abdomen/pelvis series were reconstructed with filtered back projection (FBP)
      alone, combined 40% adaptive statistical iterative reconstruction & FBP (ASIR40),
      and model-based iterative reconstruction (MBIR) [(resolution-preference 05 (RP05)
      and RP20 in the thorax and RP05 and noise-reduction 05 (NR05) in the abdomen)].
      Two readers rated image quality quantitatively and qualitatively. RESULTS: In
      thoracic CT, objective image noise on MBIR RP05 data sets outperformed FBP at
      200, 100, 50 and 10 mA and outperformed ASIR40 at 50 and 10 mA (p < 0.001). MBIR
      RP20 outperformed FBP at 50 and 10 mA and outperformed ASIR40 at 10 mA (p <
      0.001). Compared with both FBP and ASIR40, MBIR RP05 demonstrated significantly
      better signal-to-noise ratio (SNR) at 10 mA. In abdomino-pelvic CT, MBIR RP05 and
      NR05 outperformed FBP and ASIR at all tube current levels for objective image
      noise. NR05 demonstrated greater SNR at 200, 100, 50 and 10 mA and RP05
      demonstrated greater SNR at 50 and 10 mA compared with both FBP and ASIR. MBIR
      images demonstrated better subjective image quality scores. Spatial resolution,
      low-contrast detectability and contrast-to-noise ratio (CNR) were comparable
      between image reconstruction techniques. CONCLUSION: CTs reconstructed with MBIR
      have lower image noise and improved image quality compared with FBP and ASIR.
      These effects increase with reduced radiation exposure confirming optimal use for
      low-dose CT imaging.

PMID- 30292505
TI  - Undergraduate use of medical radiation science mobile applications.
AB  - INTRODUCTION: Despite the technologically intense nature of the medical radiation
      science (MRS) profession, literature specifically supporting the adoption of
      mobile learning in MRS education is scarce. To this aim, we explored student
      utilization of and influences for choosing MRS applications (apps, a specific
      type of mobile learning) within the Bachelor of Medical Radiation Science course
      at Charles Sturt University (CSU), Australia. Secondary objectives briefly
      investigated content reliability within selected chosen apps and overall student
      willingness to embrace this methodology prior to mainstream integration. METHODS:
      A mixed-method census survey was delivered to 415 enrolled students using the
      software Survey Monkey to compile responses to 28 questions. Inclusion criteria
      included students who owned a smartphone or tablet and who used any apps listed
      on the survey. RESULTS: Among the 97 students who completed the survey, 37%
      (36/97) freely use MRS apps at least weekly (70%, 21/30), of which anatomy
      atlases were reported as most popular. Peer recommendation influenced 67% (20/30)
      of students to choose the MRS apps used. Thirty-seven percent (11/30) of students
      integrated only one method to check the accuracy of app content prior to
      download. Students who do not use MRS apps (78%, 76/97) stated they were unaware
      of this resource; however, 91% (80/88) of the respondents indicated they would
      use MRS apps if incorporated into the curriculum. CONCLUSION: The majority of CSU
      students agreed that apps offer a convenient way to engage in a variety of
      interactive content both in the classroom and on-the-go, using apps most
      pertinent to their specific curriculum and/or for revision. Students preferred to
      use MRS apps if integrated as supplemental study tools vetted by the lecturer.

PMID- 30292506
TI  - Barriers and incentives for choosing to specialise in mammography- A survey of
      Australian undergraduate diagnostic radiography students.
AB  - INTRODUCTION: There is a projected shortage of radiographers working in breast
      screening in Australia. This study aimed to examine the perceived barriers and
      potential incentives among current undergraduate diagnostic radiography students
      to train, specialise and work in mammography. METHODS: A survey was undertaken to
      assess students' experience of six modalities during both University study and
      clinical practice. Students were asked to rank their priority of which they would
      want to specialise and if training and working in mammography was an option.
      RESULTS: From 248 students invited to participate, 101 students replied to the
      survey. Students indicated that they had been taught all modalities, however not
      all students had experienced them on clinical placement. Most students had
      observed or performed ultrasound (US) (90%, 90%), Computed Tomography (CT) (97%,
      75%) and fluoroscopy (80%, 52%), though very few had experience of mammography
      (55%, 8%). US, CT, and MRI were the modalities that most students would like to
      specialise in. Male students reported being discriminated against working in
      mammography as this is "female only" work. CONCLUSION: Students have more
      clinical access to the major modalities of US, CT and MRI, and this appears to be
      a major factor into why student wish to specialise in these modalities. Role
      extension and higher wages were given as possible incentives that would make
      specialising in Mammography more appealing. The gender divide may have to be
      bridged to enable crucial recruitment as male students feel discriminated
      against.

PMID- 30292492
TI  - Behavioral Deficits at 18-22 Months of Age Are Associated with Early Cerebellar
      Injury and Cognitive and Language Performance in Children Born Extremely Preterm.
AB  - OBJECTIVE: To investigate associations in toddlers born extremely preterm (<28
      weeks) between neonatal neuroimaging and 18- to 22-month developmental and
      behavioral outcomes. STUDY DESIGN: Cohort analysis from the Eunice Kennedy
      Shriver National Institute of Child Health and Human Development Neonatal
      Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Trial
      Neuroimaging and Neurodevelopmental Outcomes Study of infants born extremely
      preterm. Subjects underwent cranial ultrasonography and near-term magnetic
      resonance imaging (MRI). At 18-22 months of corrected age, the assessment
      included the Brief Infant Toddler Social Emotional Assessment (BITSEA) Problem
      and Competence Scale scores and the Bayley Scales of Infant Development, Third
      Edition (Bayley-III). The BITSEA Problem Scale assesses dysregulation; the
      Competence Scale assesses social-emotional competence. We examined associations
      of Problem and Competence scores and positive screen rates with cranial
      ultrasonography and near-term MRI. Mean BITSEA and Bayley-III scores were
      compared using ANOVA and positive screen rates with the chi2 test. We computed
      correlations between BITSEA and Bayley-III scores. RESULTS: Of the 397 children,
      positive BITSEA screens were found in 34% for the Problem score and 26% for the
      Competence score. Presence of lesions on near-term MRI that included cerebellar
      lesions were significantly associated with lower BITSEA Competence but not with
      Problem scores; Competence scores were inversely related to the
      presence/significance of lesions. Positive screens on Competence scores and on
      both Competence and Problem scores were significantly associated with Bayley-III
      cognitive and language scores <85 (P < .001). CONCLUSIONS: Social-emotional
      competence contributes to deficits in cognitive and language development.
      Presence of injury on near-term MRI that includes cerebellar lesions is
      associated with later social-emotional competence and may be a useful predictor
      to guide early assessment and intervention. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT00063063 and NCT00233324.

PMID- 30292507
TI  - Radiographer reporting of neurological magnetic resonance imaging examinations of
      the head and cervical spine: Findings of an accredited postgraduate programme.
AB  - INTRODUCTION: To analyse the objective structured examination (OSE) results of
      the first cohorts of radiographers (n = 13) who successfully completed an
      accredited postgraduate programme in clinical reporting of neurological magnetic
      resonance imaging (MRI) examinations of the head and cervical spine. METHODS:
      Forty MRI examinations were used in the OSE which included a range of abnormal
      cases (prevalence of abnormal examinations approximated 50%) and included:
      haemorrhage, infarction, demyelination disease, abscess, mass lesions (metastatic
      deposits, meningioma, glioma, astrocytoma); and disc disease, cord compression,
      stenosis, ligament rupture, syringomyelia appearances on patients referred from a
      range of referral sources. Normal variants and incidental findings were also
      included. True/false positive and negative fractions were used to mark the
      responses which were also scored for agreement with the previously agreed
      expected answers based on agreement between three consultant radiologists'
      reports. RESULTS: The mean sensitivity, specificity and agreement rates for all
      head and cervical spine investigations (n = 520) combined were 98.86%, 98.08% and
      88.37%, respectively. The highest scoring cases were cases which included
      astrocytoma, disc protrusion with cord compression and glioma. The most common
      errors were related to syringomyelia, ligament rupture and vertebral fracture.
      CONCLUSIONS: These OSE results suggest that in an academic setting, and following
      an accredited postgraduate education programme, this group of radiographers has
      the ability to correctly identify normal MRI examinations of the head/cervical
      spine and are able to provide a report on the abnormal appearances to a high
      standard. Further work is required to confirm the clinical application of these
      findings.

PMID- 30292508
TI  - Image interpretation by radiographers in brain, spine and knee MRI examinations:
      Findings from an accredited postgraduate module.
AB  - INTRODUCTION: The aim of the study was to evaluate the performance of
      radiographers in image interpretation of magnetic resonance imaging (MRI) brain,
      spine and knee examinations following a nine-month work based postgraduate MRI
      module. METHODS: Twenty-seven participants each submitted 60 image commentaries
      taken from prospective clinical workloads. The image interpretations (n = 1620)
      comprised brain, spine, and knee MRI examinations. Prevalence of abnormal
      examinations approximated 53% (brain), 74% (spine), and 73% (knee), and included
      acute and chronic pathology, normal variants and incidental findings. Each image
      interpretation was graded against reference standard consultant radiologist
      definitive report. RESULTS: The radiographer's performance on brain image
      interpretations demonstrated mean accuracy at 86.7% (95% CI 83.4-89.3) with
      sensitivity and specificity of 84% (95% CI 80.9-86.4) and 89.7% (95% CI 86.2
      92.6) respectively. For spinal interpretations the mean accuracy was 86.4% (95%
      CI 83.4-89.0), sensitivity was 90.2% (95% CI 88.2-92), mean specificity was 75.3%
      (95% CI 69.4-80.4). The mean results for knee interpretation accuracy were 80.9%
      (95% CI 77.3-84.1), sensitivity was 83.3% (95% CI 80.8-85.5), with 74.3%
      specificity (95% CI 67.4-80.4). CONCLUSIONS: The radiographer's demonstrated
      skills in brain, spine and knee MRI examination image interpretation. These
      skills are not to replace radiologist reporting but to meet regulating body
      standards of proficiency, and to assist decision making in communicating
      unexpected serious findings, and/or extend scan range and sequences. Further
      research is required to investigate the impact of these skills on adjusting scan
      protocols or flagging urgent findings in clinical practice.

PMID- 30292509
TI  - Development and evaluation of a deep knowledge and skills based assignment: Using
      MRI safety as an example.
AB  - INTRODUCTION: Using magnetic resonance imaging (MRI) safety as an example, this
      paper discusses the development of an innovative multiple-step assignment task
      designed to increase student engagement and learning of important concepts. The
      paper also summarises student feedback about the assessment as well as thematic
      analysis of categories thought important to students. METHOD: A multi-step
      assignment was designed. Step one was the reading of a MRI safety article, step
      two was the construction and submission of 5 short answer questions believed to
      be important concepts of understanding and step three was the answering of 15
      questions compiled from all student questions by the course coordinator. The
      motivation to answer the course coordinator compiled questions was the knowledge
      that five of these questions would be in the end of course examination. At the
      completion of the assignment, students were asked to complete an anonymous on
      line questionnaire about the assignment task. Thematic analysis was used to
      gather data on what students perceived to be the most and least important
      concepts in the article. RESULTS: All students replying to the survey stated that
      they understood why MRI safety is an important topic and 79% reported this
      assignment was both a positive learning experience and provided understanding of
      the topic. Only 18% of students believed that they would have learned more
      through a formal lecture. CONCLUSION: The design of this assignment task can be
      used in any course, not just in medical radiation science, where student learning
      and understanding is critical.

PMID- 30292510
TI  - Variation in the length and structure of reports written by reporting
      radiographers: A retrospective study.
AB  - INTRODUCTION: The literature suggests that there is variation in various features
      of the written radiology report for a range of body areas and imaging modalities.
      The retrospective study presented here aims to determine if similar variation is
      demonstrated in a group of 5 reporting radiographers in a UK NHS Trust. METHODS:
      Full reports for 1530 knee radiographic examinations performed from accident and
      emergency referrals were extracted for a 12-month period from a Radiology
      Information System (RIS) into Excel. Copied into Word, the word count function
      was used for each report and the number of words and characters (without spaces)
      was returned into Excel. Average word count and word length per report, by
      radiographer, were calculated for the following sections of the report: report
      title, main body and signature. SPSS was used to perform inferential statistical
      analysis. RESULTS: A wide range in the maximum and minimum average report lengths
      (60.88 v 17.83 words) was demonstrated. Statistically significant differences (p
      < 0.05) were seen between all but one pair-wise comparison (Rad 2 v Rad 4; p =
      0.98) for the overall report length; for the length of the findings section, four
      pair-wise comparisons did not reach significance. Average word length
      demonstrated less variation. 4 out of 5 radiographers always included a report
      title; 3 out of 5 never included a report signature. There was a strong negative
      correlation between experience and report length. CONCLUSION: Variation in report
      structure and length, as well as word length, was seen, comparable to studies of
      radiologist reports. Further research is required to investigate the drivers of
      this variation, and determine if there is any clinical significance.

PMID- 30292511
TI  - An evaluation of Fracture Liaison Services in the detection and management of
      osteoporotic fragility fractures: A narrative review.
AB  - OBJECTIVES: To evaluate the current evidence for whether Fracture Liaison
      Services are being utilised effectively in the UK to aid in the prevention of
      fragility fractures. KEY FINDINGS: Radiological under-reporting and non
      standardised assessment of fragility fractures still persist, with low numbers of
      patients undergoing a risk assessment and treatment for secondary prevention of
      fracture. In order to improve care for these patients, the reporting of vertebral
      fractures must be improved and standardised in order to identify patients at
      increased risk of secondary fragility fractures. Fracture Liaison Services
      determine the need for anti-resorptive therapy for the prevention of future
      fragility fractures. Targeted treatment of at-risk patient groups has been shown
      to reduce the risk of further fracture. CONCLUSION: Fracture Liaison Services
      have been shown to be cost effective, while reducing the risk of secondary
      fractures, but they are not currently offered by all NHS providers.

PMID- 30292512
TI  - The experiences of women receiving brachytherapy for cervical cancer: A
      systematic literature review.
AB  - OBJECTIVES: To determine women's experiences of brachytherapy for cervical
      cancer. KEY FINDINGS: Nineteen studies were included for data
      extraction/synthesis. Twelve studies focussed on psychological issues, seven on
      pharmacological aspects of women's experiences. Themes of anxiety, distress,
      pain, informational needs and non-pharmacological interventions were found. Nine
      out of ten psychological studies described brachytherapy as a distressing
      experience causing anxiety and distress for most women. Non-pharmacological
      interventions were found to be effective and inexpensive adjuncts. Peri and post
      operative pharmacological management was variable, but duration of procedure was
      an important factor. CONCLUSION: Brachytherapy for gynaecological cancer causes
      varying levels of pain, anxiety and distress. To improve women's experiences
      there needs to be better pain management, patient information and the development
      of non-pharmacological interventions. Future recommendations are to develop
      clinical support guidelines, audit the quality of services and develop effective
      interventions to improve women's experiences of brachytherapy for locally
      advanced cervical cancer.

PMID- 30292513
TI  - Perspectives on the development of professionalism as experienced by radiography
      students.

PMID- 30292514
TI  - Insights into the methodology of radiography science.
AB  - INTRODUCTION: The aim of this article is to give an insight into radiography as a
      science and a discipline from the viewpoints of knowledge interest and
      methodological approach and design. METHODS: Original articles published in
      Radiography (n = 184) and the Journal of Clinical Radiography and Radiotherapy (n
      = 10) at the timeline 2015 to 3/2017 were reviewed for research focus and the
      methodology used. To abstract the results, thematisation analysis was used.
      RESULTS: Out of 194 studies analysed, 99 (50%) were found to have a technical, 80
      (42%) a practical and 15 (8%) a critical interest of knowledge. The research
      methodologies used did not rigorously fit into the methodological approach
      expected on the basis of the interest of knowledge. CONCLUSION: Radiography as a
      science seems to have mostly a technical and practical interest of knowledge, but
      somewhat critical research is also being made. It seems to be a remarkably open
      and flexible science when it comes to the use of research methodologies. More
      discussion and research on the science name and paradigm is needed in order to
      strengthen the scientific status of radiography.

PMID- 30292515
TI  - Diagnostic accuracy of Magnetic Resonance Imaging using liver tissue specific
      contrast agents and contrast enhanced Multi Detector Computed Tomography: A
      systematic review of diagnostic test in Hepatocellular Carcinoma (HCC).
AB  - OBJECTIVES: The aim of this systematic review is to investigate diagnostic
      accuracy of Magnetic Resonance Imaging (MRI) scans using liver specific tissue
      contrast media over contrast enhanced Multi Detector CT (MDCT) in diagnoses of
      Hepatocellular Carcinoma (HCC) in patients with chronic liver disease. KEY
      FINDINGS: A total of 8 diagnostic studies were identified and generally
      considered of high quality. The studies reported sufficient evidence on
      sensitivity and specificity, which was synthesised and summarised providing an
      overview of the evidence. Findings indicate that MRI scans using liver specific
      tissue contrast have a better diagnostic performance compared to contrast
      enhanced MDCT in diagnostic work-up of HCC in patients with chronic liver
      disease. CONCLUSION: The current review identified sufficient high quality
      studies reporting statistical difference (P < 0.05), to establish the superiority
      of gadoxetetic acid enhanced MRI for sensitivity and specificity in comparison to
      MDCT in the diagnosis of HCC in chronic liver disease.

PMID- 30292516
TI  - Atraumatic musculocutaneous neuropathy: A rare case caused by a proximal humeral
      bone spur.

PMID- 30292517
TI  - Muscle thickness and echo-intensity changes of the quadriceps femoris muscle
      during a strength training program.
AB  - INTRODUCTION: Ultrasound (US) has an important role in musculoskeletal (MSK)
      evaluation, allowing the study of muscle morphology and function. Muscle
      thickness (MT) and muscle echo-intensity (EI) are two important parameters that
      may quantify muscle structural adaptations to a variety of stimuli. The aim was
      to explore the potential of quantitative US imaging for assessing the adaptations
      and responses of the muscle tissue to increased contractile activity using B-mode
      US. This study was centred on the quadriceps femoris muscle contractile activity
      on MT and EI. METHODS AND MATERIALS: Twenty-eight young male adults participated
      in the study, divided in a control group and two training groups performing
      concentric or eccentric strength training, respectively. The effect of a 15-week
      strength program was studied on MT and EI in several regions of the heads of the
      quadriceps femoris using B-mode US. All images acquisitions and measurements were
      done by the same experience sonographer. RESULTS: Strength training resulted in
      an increase of MT at all muscles and sites (p < 0.05), except the VM. Strength
      training failed in changing EI in most of the quadriceps femoris, except in the
      VI and some regions of the VL. No statistically significant differences were
      observed in our quantitative US parameters between concentric and eccentric
      training (p > 0.05). CONCLUSION: These results emphasise the value of MT as a
      quantifiable muscle US method for evaluating muscle adaptation to exercise
      training. However, the inconsistency of the EI values indicates that more studies
      are needed to develop it as an accurate diagnostic tool.

PMID- 30292519
TI  - A comparative study about motivations, expectations and future plans for
      professional development in four European radiography programs.
AB  - INTRODUCTION: This study aims to compare motivations, expectations and work plans
      of students and teaching-staff from four different European radiography programs,
      it aims also to explore areas that could be included to advance post graduate
      studies. METHODS: Two different questionnaires (open- and closed-end questions)
      were applied to key-informants, students who had just completed their bachelor
      thesis and teaching-staff, to collect data regarding motivations, expectations,
      challenges and potentials for radiography education and, plans for further work.
      Descriptive statistics and thematic analysis were performed according to the
      nature of the questions. RESULTS: The response rates were 45% (students) and 68%
      (teaching-staff). The motivations to study radiography were similar between
      students: to work in a healthcare-service, helping people, manipulating high-end
      technologies, providing service while combining different knowledge (physics,
      patient-care, physiology, anatomy). 75% of the students did not reach all their
      expectations due to the lack of focused and updated content for some areas. The
      teaching-staff were expecting an extension of the radiographers' role. The
      development of advance studies in computed tomography and magnetic resonance was
      highlighted as important by students. Future work plans included: self
      improvement, continuation of studies, specialization, research and
      collaborations. CONCLUSIONS: This study increased the understanding of
      radiography education and provides insights into future perspectives.
      Participants have similar motivations, expectations and future plans.
      Improvements in education should focus on technological developments and meeting
      job market demands. Further studies should be performed to identify approaches
      that acknowledge the specific needs of each country, while also providing
      strategies to harmonize radiography education in Europe.

PMID- 30292518
TI  - Assessment of left ventricular ejection fraction with late-systolic and mid
      diastolic cardiac phases using multi-slice computed tomography.
AB  - INTRODUCTION: Multi-slice computed tomography (MSCT) is an accurate tool for the
      assessment of left ventricular ejection fraction (LVEF). However, in order to
      reduce radiation dose, prospective acquisition protocols are currently used, in
      which the end-systole and end-diastole are not scanned. Our aim was to study the
      accuracy of the assessment of LVEF using fixed late-systolic and mid-diastolic
      cardiac phases compared with echocardiography. METHODS: MSCT-derived LVEF was
      measured with off-line commercially available software packages, and compared
      with echocardiography-derived LVEF using the Simpson's method. LVEF was
      categorized as normal vs. abnormal (50% cut-off) and was also analyzed as a
      quantitative parameter. Bland-Altman plots and Pearson correlations were used for
      inter-technique comparisons. RESULTS: 58 patients were included. The sensitivity
      and specificity of fixed-phase MSCT when compared with echocardiography for
      detection of LVEF <=50% was 79% (95% CI = 65-89%) and 43% (10-82%).
      Misclassification was associated with older age (68 +/- 12 vs. 54 +/- 13 years, p
      < 0.01), faster heart rate (79 +/- 14 vs. 68 +/- 10 bpm, p = 0.01), and LV
      hypertrophy (86% vs. 52%, p = 0.03). The quantitative comparison revealed no
      correlation (r = 0.095, p = 0.478) and a significantly different LVEF
      (median[IQR], 57.0[50.5-63.1]% vs. 61.0[57.3-64.3]%, p = 0.03). The observed bias
      between the two methods was -3.7% with broad limits of agreement (+/-25.5%).
      CONCLUSIONS: Fixed-phase MSCT assessment using late-systole and mid-diastole
      agreed in defining normal and abnormal LVEF in 76% of patients when compared with
      echocardiography. Quantitation of LVEF by this method yielded significantly lower
      values of LVEF and showed no correlation. Thus, accurate quantitation of LVEF by
      MSCT requires the acquisition of end-systolic and end-diastolic phases.

PMID- 30292520
TI  - A study to explore opinions and attitudes of Saudi Arabian MR professionals on
      the current status of routine MR scanner quality assurance testing in the Kingdom
      of Saudi Arabia.
AB  - INTRODUCTION: Internationally it is recommended that quality assurance (QA)
      testing of MR systems is the responsibility of MR professionals to ensure
      efficient scanner performance. This study aims to explore the opinions and
      attitudes of MR professionals in the Kingdom of Saudi Arabia (KSA) regarding the
      current status of routine QA testing within MRI departments. METHODS: A
      qualitative approach was adopted, with MR professionals working in public, semi
      public and private hospitals in the KSA invited to participate in this interview
      based study. A total of 52 individual semi-structured interviews were conducted
      with purposive sampling of MR radiographers and medical physicists based at 19
      major centres across the three main geographical regions in the KSA. Data went
      through duration of coding following qualitative data analysis framework based on
      Miles and Huberman's philosophical underpinnings. RESULTS: The findings
      demonstrated that 89.5% (n = 17) of the MRI departments surveyed rely on the
      service provided by the equipment vendor in order to ensure ongoing MR scanner
      performance. Overall, the level of MR radiographer participation in weekly MR
      scanner QA testing was low (13.3%, n = 3). Lack of legal requirement,
      professional organisation and knowledge were highlighted as the principal factors
      limiting radiographer involvement in the weekly MR QA in the KSA. CONCLUSION: The
      results of this study support the establishment of a legal requirement and
      national policy in order to encourage radiographers in the KSA to take an active
      role in MRI QA testing to enable suboptimal MR scanner performance to be
      identified before it becomes clinically evident.

PMID- 30292521
TI  - Advances in offline approaches for chemically speciated measurements of trace gas
      phase organic compounds via adsorbent tubes in an integrated sampling-to-analysis
      system.
AB  - Gas-phase organic compounds across a range of volatilities, including volatile
      organic compounds (VOCs), are key components of outdoor air, indoor spaces, and a
      variety of other anthropogenic and biogenic systems. The collection of offline
      samples on adsorbent-packed tubes for analysis on laboratory instrumentation has
      been in use for decades, but with limited sensitivities and compound coverage. We
      present and evaluate our integrated sampling-to-analysis system that enables
      offline detailed chemical characterization of multi-faceted organic mixtures at
      trace concentrations. Its capabilities extend across a diverse variety of VOCs
      with different molecular features, as well as intermediate and semivolatile
      organic compounds (I/SVOCs). Samples can be collected manually or via automated
      devices that have been applied in chamber, field, and aircraft platforms. The
      laboratory instrumentation can be coupled to both a high resolution mass
      spectrometer (MS) and a traditional quadrupole MS, though performance metrics
      presented in this study are determined via the traditional MS. We demonstrate
      capabilities for detailed chemical characterization and routine performance for a
      wide range of compound functionalities at sub-part per trillion (ppt)
      concentrations, and as low as <100 parts per quadrillion (ppq), yielding 3300
      observed unique compound peaks in a single indoor air sample. These limits of
      detection and compound coverage were accomplished through a holistic optimization
      of the entire system and lifecycle of adsorbent tubes. We present our best
      practices for all aspects of tube production, handling, sampling, and analysis,
      and an examination of commercially-available materials and our custom adsorbent
      tubes using a diverse mix of VOC, IVOC, and SVOC standards, including difficult
      to measure analytes across a range of polarities and functionalities. In many
      aspects, the commercially-available materials and tube conditioners tested were
      insufficient for achieving low-ppt measurements.

PMID- 30292522
TI  - A fully automated approach for the analysis of 37 psychoactive substances in raw
      wastewater based on on-line solid phase extraction-liquid chromatography-tandem
      mass spectrometry.
AB  - This work presents a multi-residue method for the simultaneous determination of
      37 legal and illicit psychoactive substances in wastewater, including the most
      common illicit drugs (cocaine-related compounds, amphetamine-type stimulants,
      hallucinogens, opiates/opioids, and cannabinoids), new psychoactive substances
      (two synthetic cathinones, the synthetic opioid AH-7921, and the
      arylcyclohexylamine methoxetamine), and legal but controlled psychoactive
      substances (stimulants, benzodiazepines, antidepressants, sedatives,
      antipsychotics, and hypnotics). To this end a fully automated analytical approach
      based on solid phase extraction coupled in series to liquid chromatography tandem
      mass spectrometry detection (on-line SPE- LC-MS/MS) was used. The methodology
      developed was validated in terms of linearity, recovery, repeatability, and
      sensitivity in wastewater. Method linearity was between 0.1 ng/L (or the analyte
      limit of quantification if higher) and 2,000 ng/L (10,250 ng/L in the case of
      caffeine). Absolute recoveries were variable (between 5% and 132%), depending on
      the analyte. However, the use of isotopically labeled compounds corrected for
      analyte losses during the extraction process and matrix effects (relative
      recoveries within the range of 80-120%). Repeatability of the method was
      satisfactory for all analytes, with RSD values lower than 13% for most compounds.
      Limits of detection and quantification in wastewater were below 7 and 23 ng/L,
      respectively, for all analytes except lormetazepam (10 and 32 ng/L), caffeine (13
      and 44 ng/L), and the cannabinoids 11-nor-9-carboxy- Delta9-tetrahydrocannabinol
      (18 and 61 ng/L) and 11-hydroxy-Delta9- tetrahydrocannabinol (69 and 228 ng/L).
      The method was applied to the analysis of wastewater samples collected daily in
      Barcelona for one week. Twenty-five of the 37 analytes were detected in the
      samples analyzed. Average concentrations ranged from 7 ng/L in the case of
      zolpidem to 54 MUg/L in the case of caffeine.

PMID- 30292523
TI  - Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after
      exercise.
AB  - OBJECTIVE: Hypothalamic Pro-opiomelanocortin (POMC) and Neuropeptide Y/Agouti
      Related Peptide (NPY/AgRP) neurons are critical nodes of a circuit within the
      brain that sense key metabolic cues as well as regulate metabolism. Importantly,
      these neurons retain an innate ability to rapidly reorganize synaptic inputs and
      electrophysiological properties in response to metabolic state. While the
      cellular properties of these neurons have been investigated in the context of
      obesity, much less is known about the effects of exercise training. METHODS: In
      order to further investigate this issue, we utilized neuron-specific transgenic
      mouse models to identify POMC and NPY/AgRP neurons for patch-clamp
      electrophysiology experiments. RESULTS: Using whole-cell patch-clamp
      electrophysiology, we found exercise depolarized and increased firing rate of
      arcuate POMC neurons. The increased excitability of POMC neurons was concomitant
      with increased excitatory inputs to these neurons. In agreement with recent work
      suggesting leptin plays an important role in the synaptic (re)organization of
      POMC neurons, POMC neurons which express leptin receptors were more sensitive to
      exercise-induced changes in biophysical properties. Opposite to effects observed
      in POMC neurons, NPY neurons were shunted toward inhibition following exercise.
      CONCLUSIONS: Together, these data support a rapid reorganization of synaptic
      inputs and biophysical properties in response to exercise, which may facilitate
      adaptations to altered energy balance and glucose metabolism.

PMID- 30292524
TI  - Nebulized Tranexamic Acid Use for Pediatric Secondary Post-Tonsillectomy
      Hemorrhage.
AB  - Post-tonsillectomy hemorrhage is a frequent occurrence in the emergency
      department, and management of potentially life-threatening and ongoing bleeding
      by the emergency physician is challenging. Limited evidence-based guidelines
      exist, and practice patterns vary widely. We administered nebulized tranexamic
      acid to achieve hemostasis in a pediatric patient with associated bleeding
      cessation prior to definitive operative management.

PMID- 30292525
TI  - Native english speakers and English as a Foreign Language (EFL) students'
      performance and notetaking in a Doctor of pharmacy health systems course.
AB  - BACKGROUND: Academic pharmacy programs continue to diversify in student
      population. While the challenges of non-native language speakers have been
      opined, there is scant research on their performance in comparison with native
      language speakers nor is there much information on differences in the processes
      used in academic preparation, such as on note-taking. OBJECTIVE: The objectives
      of this study were to: (1) identify differences in test performance between
      native English speakers and students for whom English is a foreign language (EFL)
      in a health systems PharmD course, and (2) examine differences between these two
      groups in note-taking attitudes and behaviors. METHODS: Students' self-reported
      data as native English-speaking or EFL were acquired from the University Office
      of Admissions. Students' performance was measured on examinations covering
      lecture content, with independent-sample t tests discerning differences on all 3
      examinations. T-tests were also used to ascertain differences on examination
      scores by student race/ethnicity and on differences in their response to a survey
      on attitudes, behaviors, and satisfaction with note-taking. RESULTS: EFL students
      scored significantly lower on the latter two examinations and on the average of
      the three examinations by over 7%. EFL students reported lower satisfaction with
      the accuracy and completeness of their notes and indicated that peers were less
      likely to borrow their notes. They also reported being more likely to be
      distracted in class by peers' laptop note-taking, even though there were many
      similarities between the two groups in how they approached note-taking.
      CONCLUSIONS: EFL student performance was lower than that of native English
      speakers on examinations. EFL students were less satisfied with the quality of
      their notes. Further research is needed to identify effective strategies for
      improving the learning experience of EFL students. Academic administration can
      identify mechanisms to facilitate a learning environment conducive for their
      success.

PMID- 30292526
TI  - Management of bleeding in major burn surgery.
AB  - Major burn surgery is often associated with excessive bleeding and massive
      transfusion, and the development of a coagulopathy during major burn surgery is
      associated with increased morbidity and mortality. The aim of this study was to
      review the literature on intraoperative haemostatic resuscitation of burn
      patients during necrectomy to reveal strategies applied for haemostatic
      monitoring and resuscitation. We searched PubMed, EMBASE, and CENTRAL for studies
      published in the period 2006-2017 concerning bleeding issues related to burn
      surgery i.e. coagulopathy, transfusion requirements and clinical outcomes. In a
      broad search, a total of 1375 papers were identified. 124 of these fulfilled the
      inclusion criteria, and six of these were included for review. The literature
      confirmed that transfusion requirements increases with burn injury severity and
      that haemostatic monitoring by TEG(r) (thrombelastography) or ROTEM(r)
      (rotational thromboelastometry) significantly decreased intraoperative
      transfusions and was useful in predicting and goal-directing haemostatic therapy
      during excision surgery. Resuscitation of bleeding during major burn surgery in
      many instances was neither standardized nor haemostatic. We suggest that
      resuscitation should aim for normal haemostasis during the bleeding phase through
      close haemostatic monitoring and resuscitation. Randomised controlled trials are
      highly warranted to confirm the benefit of this concept.

PMID- 30292527
TI  - Correction to Lancet Oncol 2018; 19: 1289-306.

PMID- 30292528
TI  - Effect of nurse staffing on rehospitalizations and emergency department visits
      among short-stay nursing home residents: A Cross-sectional study using the US
      Nursing Home Compare database.
AB  - The aim of this study was to examine the effect of nurse staffing on both
      rehospitalizations and emergency department emergency department visits among
      short-stay nursing home residents in the United States. Data for 11,132 US
      nursing homes were drawn from the 2016 Nursing Home Compare. We found that the
      Five-Star Quality Rating System's staffing rating is a significant predictor for
      the rates of rehospitalization and emergency department visit among short-stay
      nursing home residents. The results also showed the importance of registered
      nurse staffing in nursing home caring for short-stay residents. Administrators
      and policy-makers can employ the findings to formulate management strategies that
      will reduce rehospitalizations and emergency department visits among nursing home
      residents.

PMID- 30292529
TI  - The influence of the middle hepatic vein and its impact on outcomes in right lobe
      living donor liver transplantation.
AB  - BACKGROUND: In adult right lobe living donor liver transplantation, the decision
      to include the middle hepatic vein (MHV) remains controversial. METHODS: A
      retrospective analysis of 50 R-LDLTs between January 2008 and June 2016 was
      performed. RESULTS: Twenty-one procedures were performed using a MHV+ graft
      (42.0%) and 29 procedures using a MHV- graft (58%). MHV- donors were taller (173
      vs 166 cm, p = 0.004) with a larger standard liver volume (1351 vs 1245 mls, p =
      0.014) compared to MHV+ donors. The duration of operation for donors was
      significantly longer in the MHV+ group (530 (313-975) mins) compared to the MHV-
      group (489 (336-708) mins) (p = 0.029). Similarly, the operative time for
      recipients was longer in the MHV+ group (660 (428-831) mins) compared to MHV-
      (579 (359-1214) mins) (p = 0.023). MHV- grafts were heavier compared to MHV+
      grafts (918 vs 711 g, p = 0.017). Recipient mortality rates and Kaplan-Meier
      survival analysis were comparable (p = 0.411). All donors were well at last
      review. CONCLUSION: Both MHV+ and MHV- grafts are safe for the donor and
      recipient. The decision to take the MHV should be based on specific donor
      recipient characteristics.

PMID- 30292530
TI  - Novel method of fitting of children with auditory brainstem implants.
AB  - OBJECTIVES: To develop a reliable and objective fitting method for use with young
      children with an auditory brainstem implant (ABI). MATERIALS AND METHODS:
      Subjects were 17 young children implanted with an ABI with the mean age 2 years
      and 4 months (8-64 months). Evoked auditory brainstem response (eABR)
      measurements were performed intraoperatively and at activation in order to record
      the auditory response and non-auditory side effects. Each child was tested to
      observe any subjective responses to the electric stimuli and non-auditory side
      effects. All children were fitted based on the postoperative eABR. The minimum
      follow up time was 12 months. RESULTS: Intraoperatively an eABR could be obtained
      in all children. The responses were recordable from 75-100% of all electrodes. At
      initial stimulation eABR were recordable in all children. The eABR was obtained
      in 79.7% of all electrodes (25-100%) with a mean eABR threshold of 22.3 nC. eABR
      without any non-auditory stimulation was recorded on all electrodes in 11
      children. Mixed eABR and non-auditory responses were recorded on 2-6 electrodes
      in 6 children. The subjective auditory responses for at least 1 electrode were
      noted in 15 children. In the 2 remaining cases the auditory response was obtained
      only when the device was activated. In all children the subjective responses were
      within the estimated dynamic range for each electrode. Each child was able to
      accept up to 100% of volume of the created map. The non-auditory response was
      observed only on children and electrodes with mixed eABR and non-auditory
      responses. The mean CAP score at 6 months after the activation was 2.4 (1-4).
      CONCLUSIONS: eABR seems to be a reliable tool to judge ABI electrode placement
      and a reliable method for fitting of young children with an ABI. The data suggest
      that eABR-based fitting helps children to more quickly achieve auditory
      perception and development.

PMID- 30292531
TI  - Corrigendum to "Filtered sunlight, solar powered phototherapy and other
      strategies for managing neonatal jaundice in low-resource settings" [Early Hum.
      Dev. 114 (2017 Nov) 11-15].

PMID- 30292532
TI  - A mathematical model of the biochemical network underlying left-right asymmetry
      establishment in mammals.
AB  - The expression of the TGF-beta protein Nodal on the left side of vertebrate
      embryos is a determining event in the development of internal-organ asymmetry. We
      present a mathematical model for the control of the expression of Nodal and its
      antagonist Lefty consisting entirely of realistic elementary reactions. We
      analyze the model in the absence of Lefty and find a wide range of parameters
      over which bistability (two stable steady states) is observed, with one stable
      steady state a low-Nodal state corresponding to the right-hand developmental
      fate, and the other a high-Nodal state corresponding to the left. We find that
      bistability requires a transcription factor containing two molecules of
      phosphorylated Smad2. A numerical survey of the full model, including Lefty,
      shows the effects of Lefty on the potential for bistability, and on the
      conditions that lead to the system reaching one or the other steady state.

PMID- 30292533
TI  - Increasing complexity: Mechanical guidance and feedback loops as a basis for self
      organization in morphogenesis.
AB  - The article is devoted to physical views on embryo development as a combination
      of structurally stable dynamics and symmetry-breaking events in the general
      process of self-organization. The first corresponds to the deterministic aspect
      of embryo development. The second type of processes is associated with sudden
      increase of variability in the periods of symmetry-breaking, which manifests
      unstable dynamics. The biological basis under these considerations includes
      chemokinetics (a system of inductors, repressors, and interaction with their next
      surrounding) and morphomechanics (i.e. mechanotransduction, mechanosensing, and
      related feedback loops). Although the latter research area is evolving rapidly,
      up to this time the role of mechanical properties of embryonic tissues and
      mechano-dependent processes in them are integrated in the general picture of
      embryo development to a lesser extent than biochemical signaling. For this
      reason, the present article is mostly devoted to experimental data on
      morphomechanics in the process of embryo development, also including analysis of
      its limitations and possible contradictions. The general system of feedback-loops
      and system dynamics delineated in this review is in large part a repetition of
      the views of Lev Beloussov, who was one of the founders of the whole areas of
      morphomechanics and morphodynamics, and to whose memory this article is
      dedicated.

PMID- 30292534
TI  - A fiduciary marker-based framework to assess heterogeneity and anisotropy of
      right ventricular epicardial strains in the beating ovine heart.
AB  - Quantifying ventricular deformation in health and disease is critical to our
      understanding of normal heart function, heart disease mechanisms, and the effect
      of medical treatments. Imaging modalities have been developed that can measure
      ventricular deformation non-invasively. However, because of the small thickness,
      complex shape, and anatomic position of the right ventricle, using these
      technologies to determine its deformation remains challenging. Here we develop a
      first fiduciary marker-based method to assess heterogeneity and anisotropy of
      right ventricular epicardial strain across the entire free wall. To this end, we
      combine a high-density array of sonomicrometry crystals implanted across the
      entire right ventricular epicardial surface with a subdivision surface algorithm
      and a large deformation kinematics framework. We demonstrate our approach on four
      beating ovine hearts and present a preliminary regional analysis of
      circumferential, longitudinal, and areal strain. Moreover, we illustrate maps of
      the same strains across the entire right ventricular epicardial surface to
      highlight their spatial heterogeneity and anisotropy. We observe in these animals
      that RV epicardial strains vary throughout the cardiac cycle, are heterogeneous
      across the RV free wall, and are anisotropic with larger compressive strains,
      i.e., contraction, in the longitudinal direction than in the circumferential
      direction. Average peak compressive strains vary by region between -3.34% and 
      8.29% in circumferential direction, and -4.02% and -10.57% in longitudinal
      direction. In summary, we introduce an experimental framework that will allow us
      to study disease- and device-induced deformations, and long-term consequences of
      these deformations, including heterogeneous and anisotropic effects.

PMID- 30292535
TI  - Interpersonal brain synchronization associated with working alliance during
      psychological counseling.
AB  - The mechanisms underlying behavioral synchrony during psychological counseling
      are not clear. Recent research has provided evidence that pervasive synchrony is
      associated with interpersonal brain synchronization (IBS) and possibly
      contributes to the positive working alliance-the degree to which the counseling
      dyads engage in collaborative and purposive work. Our study explored the IBS
      between the clients and the counselors using functional near-infrared
      spectroscopy (fNIRS)-based hyperscanning. Thirty-four participants (as clients)
      were randomly assigned either to the psychological counseling group or to the
      chatting group; three female professional counselors provided them with 40
      minutes of psychological counseling or chatting. We found better working
      alliances and increased IBS in the right temporo-parietal junction (rTPJ) between
      clients and counselors during psychological counseling (versus chatting). Such
      IBS also correlated with the bond of working alliance. To our knowledge, our work
      represents the first demonstration of fNIRS-hyperscanning measurements for
      synchronous brain activity between the clients and counselors. This study refines
      the neural explanation of behavioral synchrony during psychological counseling.

PMID- 30292536
TI  - Polymorphism of Foxp3 gene affects the frequency of regulatory T cells and
      disease activity in patients with rheumatoid arthritis in Iranian population.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease that mainly affects
      joints and characterized by chronic joint inflammation and infiltration of
      various immune cells in the synovium. Forkhead box P3 (Foxp3)-expressing
      regulatory T cells (Tregs) play a crucial role in preventing autoimmunity and
      undesirable T cell responses. However, there are controversial reports regarding
      the defective function or frequency of these cells in various studies, which may
      be in part related to different polymorphisms of FoxP3 and influence of ethnicity
      on these differences. Therefore, the main subject of this study was to evaluate
      the association of Foxp3 gene polymorphism and Treg frequency in Iranian patients
      with RA. Accordingly, 240 RA patients diagnosed according to American college of
      rheumatology 2010 criteria and 240 normal subjects were recruited for this study.
      Genomic DNA was genotyped for -3279 C/A Foxp3 gene SNP using the PCR-RFLP. The
      frequency of Tregs and serum levels of interleukin (IL)-10, transforming growth
      factor (TGF)-beta, anti-cyclic citrullinated peptide (CCP) and rheumatoid factor
      (RF) were determined by flow cytometry and ELISA methods, respectively. The
      results showed a significant association of Foxp3 -3279 A allele with augmented
      risk of RA in Iranian patients compared to wild-type allele. While the
      frequencies of CA and AA genotypes were significantly higher in patients, RA
      patients with AA genotype had a significant lower frequency of Tregs compared to
      patients with CC and CA genotypes. Consistently, TGF-beta and IL-10 significantly
      diminished in patients with AA genotype compared to patients with CA and CC
      genotypes. Our findings indicated that the AA genotype of Foxp3 in RA patients is
      associated with downregulation of Tregs and susceptibility to RA in the Iranian
      population.

PMID- 30292537
TI  - Predicting hospital associated disability from imbalanced data using supervised
      learning.
AB  - Hospitalization of elderly patients can lead to serious adverse effects on their
      functional capability. Identifying the underlying factors leading to such adverse
      effects is an active area of medical research. The purpose of the current paper
      is to show the potential of artificial intelligence in the form of machine
      learning to complement the existing medical research. This is accomplished by
      studying the outcome of hospitalization of elderly patients as a supervised
      learning task. A rich set of features characterizing the medical and social
      situation of elderly patients is leveraged and using confusion matrices,
      association rule mining, and two different classes of supervised learning
      algorithms, it is shown that the need for help and supervision are the most
      important features predicting whether these patients will return home after
      hospitalization. Such findings can help to improve hospitalization and
      rehabilitation of elderly patients.

PMID- 30292538
TI  - Towards a modular decision support system for radiomics: A case study on rectal
      cancer.
AB  - Following the personalized medicine paradigm, there is a growing interest in
      medical agents capable of predicting the effect of therapies on patients, by
      exploiting the amount of data that is now available for each patient. In
      disciplines like oncology, where images and scans are available, the exploitation
      of medical images can provide an additional source of potentially useful
      information. The study and analysis of features extracted by medical images,
      exploited for predictive purposes, is termed radiomics. A number of tools are
      available for supporting some of the steps of the radiomics process, but there is
      a lack of approaches which are able to deal with all the steps of the process. In
      this paper, we introduce a medical agent-based decision support system capable of
      handling the whole radiomics process. The proposed system is tested on two
      independent data sets of patients treated for rectal cancer. Experimental results
      indicate that the system is able to generate highly performant centre-specific
      predictive model, and show the issues related to differences in data sets
      collected by different centres, and how such issues can affect the performance of
      the generated predictive models.

PMID- 30292539
TI  - The Birth of the 3D Genome during Early Embryonic Development.
AB  - The 3D structure of chromatin in the nucleus is important for the regulation of
      gene expression and the correct deployment of developmental programs. The
      differentiation of germ cells and early embryonic development (when the zygotic
      genome is activated and transcription is taking place for the first time) are
      accompanied by dramatic changes in gene expression and the epigenetic landscape.
      Recent studies used Hi-C to investigate the 3D chromatin organization during
      these developmental transitions, uncovering remarkable remodeling of the 3D
      genome. Here, we highlight the changes described so far and discuss some of the
      implications that these findings have for our understanding of the mechanisms and
      functionality of 3D chromatin architecture.

PMID- 30292540
TI  - Corrigendum to 'Epidemiological characteristics of pediatric epistaxis presenting
      to the emergency department' International Journal of Pediatric
      Otorhinolaryngology (2017) 121-124.

PMID- 30292541
TI  - Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients
      with Macular Telangiectasia Type 2: A Randomized Clinical Trial.
AB  - PURPOSE: To test the effects of an encapsulated cell-based delivery of a
      neuroprotective agent, ciliary neurotrophic factor (CNTF), on progression of
      macular telangiectasia type 2, a neurodegenerative disease with no proven
      effective therapy. DESIGN: Randomized sham-controlled clinical trial.
      PARTICIPANTS: Ninety-nine study eyes of 67 eligible participants were enrolled.
      METHODS: Single-masked randomized clinical trial of 24 months' duration conducted
      from May 2014 through April 2017 in 11 clinical centers of retinal specialists in
      the United States and Australia. Participants were randomized 1:1 to surgical
      implantation of intravitreal sustained delivery of human CNTF versus a sham
      procedure. MAIN OUTCOME MEASURES: The primary outcome was the difference in the
      area of neurodegeneration as measured in the area of the ellipsoid zone
      disruption (or photoreceptor loss) measured on spectral-domain (SD) OCT images at
      24 months from baseline between the treated and untreated groups. Secondary
      outcomes included comparison of visual function changes between treatment groups.
      RESULTS: Among the 67 participants who were randomized (mean age, 62+/-8.9 years;
      41 women [61%]; 58 white persons [86%]), 65 (97%) completed the study. Two
      participants (3 study eyes) died and 3 participants (4 eyes) were found
      ineligible. The eyes receiving sham treatment had 31% greater progression of
      neurodegeneration than the CNTF-treated eyes. The difference in mean area of
      photoreceptor loss was 0.05+/-0.03 mm2 (P = 0.04) at 24 months. Retinal
      sensitivity changes, measured using microperimetry, were correlated highly with
      the changes in the area of photoreceptor loss (r = 0.86; P < 0.0001). The mean
      retinal sensitivity loss of the sham group was 45% greater than that of the
      treated group (decrease, 15.81+/-8.93 dB; P = 0.07). Reading speed deteriorated
      in the sham group (-13.9 words per minute) with no loss in the treated group (P =
      0.02). Serious adverse ocular effects were found in 2 of 51 persons (4%) in the
      sham group and 2 of 48 persons (4%) in the treated group. CONCLUSIONS: In
      participants with macular telangiectasia type 2, a surgical implant that released
      CNTF into the vitreous cavity, compared with a sham procedure, slowed the
      progression of retinal degeneration. Further research is needed to assess longer
      term clinical outcomes and safety.

PMID- 30292542
TI  - Risk of Systemic Adverse Events Associated with Intravitreal Anti-VEGF Therapy
      for Diabetic Macular Edema in Routine Clinical Practice.
AB  - PURPOSE: Intravitreal anti-vascular endothelial growth factor (VEGF)
      pharmacotherapy has become standard of care for the management of diabetic
      macular edema (DME). The systemic safety profile of this treatment in routine
      clinical practice remains incompletely understood. We used a large claims
      database to investigate the risk of systemic serious adverse events (SAEs) in
      patients receiving anti-VEGF for DME compared with controls treated with macular
      laser photocoagulation or intravitreal corticosteroid. DESIGN: Retrospective
      cohort study. PARTICIPANTS: By using a large U.S. insurance database, we
      identified privately insured and Medicare Advantage patients aged >=18 years
      treated with anti-VEGF for DME between January 1, 2006, and December 31, 2015,
      along with control patients receiving macular laser or corticosteroid. We
      included patients with 1 year of medical coverage before initial DME treatment.
      METHODS: We assessed associations between treatment modalities and predefined
      systemic outcomes using Cox proportional hazards regression. We performed 2
      separate comparisons, one between anti-VEGF and macular laser and one between
      anti-VEGF and corticosteroid. We used inverse propensity score weighting for the
      first comparison to account for treatment selection bias. For the second, we used
      2:1 propensity score matching on demographics, year, and baseline comorbidities
      because of the smaller number of corticosteroid-treated patients. MAIN OUTCOME
      MEASURES: Risk of cerebrovascular disease, myocardial infarction, major bleeding,
      and all-cause hospitalization occurring within 6 months of initial DME treatment
      as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of
      23 348 patients receiving treatment for DME met inclusion criteria; 13 365
      received macular laser, 9219 received intravitreal anti-VEGF, and 764 received
      intravitreal corticosteroid as initial treatment. Anti-VEGF pharmacotherapy was
      not associated with an increased hazard of cerebrovascular disease (HR, 0.96; 95%
      CI, 0.65-1.41; P = 0.83), major bleeding (HR, 1.23; 95% CI, 0.76-1.99; P = 0.41),
      or myocardial infarction (HR, 1.03; 95% CI, 0.73-1.44; P = 0.88) when compared
      with macular laser for DME; however, there was an increased hazard of post
      treatment all-cause hospital admission (HR, 1.17; 95% CI, 1.05-1.30; P = 0.01).
      The rates of all primary systemic SAE outcomes were similar after treatment with
      anti-VEGF versus corticosteroid (P > 0.05 for all). CONCLUSIONS: We identified no
      increased risk of cerebrovascular disease, myocardial infarction, or major
      bleeding within 6 months after intravitreal anti-VEGF pharmacotherapy for the
      treatment of DME in routine clinical practice. A potential difference in all
      cause hospitalization may merit further investigation.

PMID- 30292543
TI  - The analysis of cell-free DNA concentrations and integrity in serum of initial
      and treated of lymphoma patients.
AB  - OBJECTIVE: To evaluate cell-free DNA (cfDNA) in plasma as a promising biomarker
      for lymphoma, altered levels of cfDNA and its association with clinical
      parameters are investigated in patients suffered from lymphomas. METHODS:
      Peripheral blood specimens were collected from 60 patients with lymphoma during
      initial diagnosis and those of another 107 patients with lymphoma during treated
      stage were also collected, 93 healthy volunteers were selected as control group.
      Quantitative PCR was used to detect cfDNA level in each group, cfDNA level in
      different groups was analyzed to understand its relationship with lymphoma
      patients' clinical features. After correlation analysis between cfDNA and
      clinical characteristics, Receiver operator characteristic curve was performed to
      analyze sensitivity and specificity of cfDNA and LDH. RESULTS: cfDNA
      concentration and integrity in initial stage of lymphoma patients were
      significantly higher than those in treated stage, and cfDNA concentration in
      treated phase was significantly higher than cfDNA concentration in control group.
      There was no significant difference in cfDNA integrity at treated stage compared
      with control group. There was no significant correlation between patient's age,
      gender, extranodal invasion and lymphoma pathological type and cfDNA
      concentration and integrity; In contrast, there was a significant correlation
      between ECOG score, LDH content, Ann Arbor stage, IPI, B-symptoms, Ki-67
      expression and radiotherapy and cfDNA concentration and integrity, both at the
      time of initial diagnosis and treated stage. cfDNA concentration detection is an
      optimal diagnostic indicator, followed by cfDNA integrity detection, the
      sensitivity and specificity of both are superior to the traditional LDH
      detection. CONCLUSION: cfDNA level is significantly increased in lymphomas
      patient plasma and may help lymphoma screening. cfDNA level may serve as a
      potential indicator of lymphomas treatment efficacy.

PMID- 30292544
TI  - Short communication: Effect of refrigerated storage on the pH and bacterial
      content of pasteurized human donor milk.
AB  - Once pasteurized donor milk is thawed for its administration to a preterm or sick
      neonate, and until it is administered, it is kept refrigerated at 4 to 6 degrees
      C for 24 h. After this time, unconsumed milk is discarded. This time has not been
      extended, primarily because of the concern of bacterial contamination. The aim of
      this study was to determine the changes in pH and bacterial count when
      pasteurized donor milk was kept under refrigeration for a prolonged period (14
      d). In this prospective study, 30 samples of pasteurized donor milk from 18
      donors were analyzed. Milk was handled following the regular operating protocols
      established in the neonatal unit and was kept refrigerated after thawing. pH
      measurements and bacteriology (on blood agar and MacConkey agar plates) were
      performed on each sample at time 0 (immediately after thawing) and then every day
      for 14 d. Changes in pH of samples over time were evaluated with linear mixed
      effects regression models. A slow but gradual increase in milk pH was observed
      starting from the first day [mean (+/-SD) pH of 7.30 (+/-0.18) at time 0 and 7.69
      (+/-0.2) on d 14]. No bacterial growth was observed in any of the samples
      throughout the complete trial except in one sample, in which Bacillus flexus was
      isolated. In conclusion, pasteurized human donor milk maintains its
      microbiological quality when properly handled and refrigerated (4-6 degrees C).
      The slight and continuous increase in milk pH after the first day could be due to
      changes in the solubility of calcium and phosphate during refrigerated storage.

PMID- 30292545
TI  - Supplementation effects of pomegranate by-products on oxidative status, metabolic
      profile, and performance in transition dairy cows.
AB  - Recent studies demonstrated a high antioxidant capacity for pomegranate
      components due to their rich bioactive compounds, such as conjugated fatty acids
      and phenolics. The objective of the present study was, therefore, to assess
      whether pomegranate seed or pomegranate seed pulp (peel + seed) supplementation
      could be effective to improve antioxidant status, and hence metabolic profile and
      performance in periparturient dairy cows. After a 1-wk pretreatment period,
      Holstein cows (primiparous n = 12, multiparous n = 18) were assigned to 3 dietary
      treatments from 25 d before expected calving through 25 d postcalving. The
      dietary treatments included (1) control (CON); (2) diet supplemented with
      pomegranate seeds (PS; 400 g/cow per day); and (3) diet supplemented with
      pomegranate seed pulp (PSP; 400 g of seeds/cow per day + 1200 g of peels/cow per
      day). Compared with CON, supplementation with either PS or PSP had no effects on
      dry matter intake, rumen fermentation, and plasma concentrations of cholesterol,
      total protein, globulin, and aspartate amino transferase, but enhanced plasma
      total antioxidant activity, and lowered triacylglycerol, free fatty acids (FFA),
      and beta-hydroxybutyrate at both pre- and postpartum periods. Plasma
      concentration of glucose, albumin, malondialdehyde (MDA) and blood superoxide
      dismutase (SOD) activity were not affected by dietary treatments at prepartum,
      whereas SOD activity increased and glucose, albumin, MDA, and FFA-to-albumin
      ratio decreased by feeding both by-products at postpartum period. In contrast to
      PS, supplementing PSP resulted in a greater decrease in plasma glucose and
      triacylglycerol concentration and higher increase in SOD activity. Energy- and
      fat-corrected milk yields were higher in cows fed PSP diet compared with those
      fed CON or PS diets, but content of milk fat, protein, and lactose were similar
      across the dietary treatments. These findings indicated that dietary pomegranate
      by-products supplementation, in particular PSP, could improve antioxidant status,
      which was associated with a decline in lipid oxidation (FFA and beta
      hydroxybutyrate) and peroxidation (MDA) and an enhancement in glucose utilization
      as well as fat-corrected milk yield.

PMID- 30292546
TI  - Estimation of circulating bovine leukemia virus levels using conventional blood
      cell counts.
AB  - Bovine leukemia virus (BLV) is widely prevalent in Japanese dairy farms. To
      control BLV infections in Japan, segregating or managing cows according to their
      proviral load (PVL) is a rational strategy. This study was conducted to establish
      a quantitative procedure for estimating blood PVL per microliter using a
      statistical model to offer a cost-effective alternative to the conventional
      quantitative real-time PCR method. In total, 250 Holstein cows infected with BLV
      were identified from 10 commercial dairy farms. Information on age was collected
      and blood samples were tested for white blood cell and lymphocyte counts and PVL
      using PCR. Generalized linear models with quasi-Poisson errors were used to
      estimate PVL by selecting age, logarithm of lymphocyte count, and their
      interaction term as explanatory variables. To evaluate the model, blood samples
      of 92 BLV-infected Holstein cows from 2 other commercial dairy farms were tested,
      and measured PVL values were compared with estimated PVL values by the model. The
      logPVL per microliter was modeled by positive associations with log lymphocyte
      count and age and a negative association with the interaction term. In the
      evaluation, measured PVL values had a strong correlation with estimated PVL
      values (Spearman's rho = 0.87). In conclusion, our model provides a cost
      effective and more rapid alternative to the conventional method to facilitate
      test and segregation or management of BLV-suspected cows.

PMID- 30292547
TI  - Short communication: Multi-component interactions causing solidification during
      industrial-scale manufacture of pre-crystallized acid whey powders.
AB  - Acid whey (AW) is the liquid co-product arising from acid-induced precipitation
      of casein from skim milk. Further processing of AW is often challenging due to
      its high mineral content, which can promote aggregation of whey proteins, which
      contributes to high viscosity of the liquid concentrate during subsequent lactose
      crystallization and drying steps. This study focuses on mineral precipitation,
      protein aggregation, and lactose crystallization in liquid AW concentrates (~55%
      total solids), and on the microstructure of the final powders from 2 independent
      industrial-scale trials. These AW concentrates were observed to solidify either
      during processing or during storage (24 h) of pre-crystallized concentrate. The
      more rapid solidification in the former was associated with a greater extent of
      lactose crystallization and a higher ash-to-protein ratio in that concentrate.
      Confocal laser scanning microscopy analysis indicated the presence of a loose
      network of protein aggregates (<=10 um) and lactose crystals (100-300 um)
      distributed throughout the solidified AW concentrate. Mineral-based precipitate
      was also evident, using scanning electron microscopy, at the surface of AW powder
      particles, indicating the formation of insoluble calcium phosphate during
      processing. These results provide new information on the composition- and process
      dependent physicochemical changes that are useful in designing and optimizing
      processes for AW.

PMID- 30292548
TI  - Optimized cultural conditions of functional yogurt for gamma-aminobutyric acid
      augmentation using response surface methodology.
AB  - Yogurt, a functional dairy food product, is an effective medium for delivering
      beneficial functional ingredients. One ingredient, gamma-aminobutyric acid
      (GABA), has growing appeal in the development of functional foods for its
      potential in reducing the risk of diabetes, hypertension, and stress as a
      bioactive agent. However, the concentration of GABA in existing food products is
      remarkably low. We developed a functional yogurt rich in GABA using Streptococcus
      thermophilus fmb5. The GABA yield of yogurt was enhanced by optimization of
      culture conditions using single factor and response surface methods. The results
      showed that culture temperature, monosodium glutamate concentration, and culture
      time are the 3 main factors that affect GABA yield. The optimal culture
      conditions were determined as follows: 38.8 degrees C for culture temperature, 20
      g/L of monosodium glutamate, and 120 h of culture time. Under the above optimal
      conditions, the actual yield of GABA production was maximized at 9.66 g/L, which
      was 1.2 times or higher than that of from any single factor treatment. The GABA
      concentration, viable bacteria number, and water-holding capacity of GABA-rich
      yogurt were stable throughout the whole storage time. The results show that
      producing yogurt with Streptococcus thermophilus fmb5 and the optimized culture
      conditions will achieve high GABA concentrations that maximize health benefits to
      consumers.

PMID- 30292549
TI  - Randomized clinical trial to evaluate the efficacy of prostaglandin F2alpha to
      treat purulent vaginal discharge in lactating dairy cows.
AB  - The objectives of this study were (1) to assess the effect of purulent vaginal
      discharge (PVD) on reproductive performance using a 4-point vaginal discharge
      score (VDS) and (2) to evaluate the effect of PGF2alpha treatment in cows with
      PVD on reproductive performance. Holstein cows (n = 2,473) from 1 commercial
      dairy farm had their vaginal discharge scored at 32 +/- 3 d in milk (DIM) using a
      4-point scale. Cows were also scored for body condition score and had their
      ovaries examined using transrectal ultrasound. A VDS-2 or greater was used to
      define PVD. Cows with PVD were assigned to receive 2 doses of 500 ug of PGF2alpha
      analogue (n = 277; Cloprostenol; PGF Veyx forte, Veyx Pharma Ltd., Schwarzenborn,
      Germany) 14 d apart (odd ear tag number) or remained untreated (n = 272; even ear
      tag number). All cows not detected in estrus at 90 +/- 3 DIM were enrolled into a
      timed artificial insemination (AI) protocol. The effect of VDS and the effect of
      PGF2alpha in cows with PVD on reproductive performance were evaluated separately.
      First service conception risk (FSCR), time to first AI, and time to pregnancy
      were used as indicators for reproductive performance. Data were analyzed with
      Cox's regression and mixed logistic models. The prevalence of PVD was 22.2%
      (548/2,473). We detected an interaction of parity and VDS for FSCR and time to
      pregnancy. In primiparous cows, VDS had no effect on FSCR and time to pregnancy.
      In multiparous cows, VDS had an effect on FSCR and time to pregnancy. Multiparous
      cows having a VDS-2 or a VDS-3 had decreased odds of pregnancy at first AI
      compared with cows having a VDS-0. Multiparous cows with VDS-1 or VDS-3 had a
      decreased hazard of conceiving within 200 DIM. The treatment effect of PGF2alpha
      was conditional on parity. In primiparous animals with PVD without a corpus
      luteum present at 32 DIM, treatment with PGF2alpha reduced FSCR. Irrespective of
      the presence of a corpus luteum, treatment with PGF2alpha decreased the hazard of
      conceiving within 200 DIM in primiparous cows. Although multiparous cows with PVD
      treated with PGF2alpha had increased odds of pregnancy at first AI, no treatment
      effect was observed on the hazard of conceiving within 200 DIM. Our results do
      not support the blanket use of PGF2alpha as a treatment option in postpartum
      dairy cows having PVD.

PMID- 30292550
TI  - Production of dairy cows fed distillers dried grains with solubles in low- and
      high-forage diets.
AB  - The objective of the study was to investigate the effects of dietary forage and
      distillers dried grains with solubles (DDGS) concentration on the performance of
      lactating dairy cows. Twelve Holstein cows were blocked by parity and milk
      production and assigned to replicated 4 * 4 Latin squares with a 2 * 2 factorial
      arrangement of treatments. Diets were formulated to contain low forage [LF; 17%
      forage neutral detergent fiber (NDF)] or high forage (HF; 24.5% forage NDF) and
      DDGS at 0 or 18% of diet dry matter. The forage portion of the diet consisted of
      80% corn silage and 20% alfalfa hay (dry matter basis). A portion of the ground
      corn and all of the expeller soybean meal and extruded soybeans from 0% DDGS
      diets were replaced with DDGS to formulate 18% DDGS diets. Overall, we found no
      interactions of forage * DDGS concentrations for any of the production measures.
      We observed no effect of diet on dry matter intake. Milk yield was greater when
      cows were fed LF diets compared with HF diets (43.3 vs. 41.5 kg/d). Milk fat
      concentration (3.03 vs. 3.38%) was lower for cows fed LF diets compared with HF
      diets, whereas protein concentration (3.11 vs. 2.98%) and yield (1.34 vs. 1.24
      kg/d) were greater for cows fed LF diets compared with HF diets. Yields of fat,
      total solids, energy-corrected milk, and feed efficiency were not affected by
      diets. Cows partitioned equally for milk, maintenance, and body reserves.
      Replacing starch from ground corn and protein from soybean feeds with DDGS at
      either 17 or 24.5% of forage NDF concentration in the diet was cost-effective and
      did not affect the production performance of lactating dairy cows.

PMID- 30292551
TI  - Lactobacillus paracasei ssp. paracasei YBJ01 reduced d-galactose-induced
      oxidation in male Kuming mice.
AB  - We investigated in vitro and in vivo antioxidant activity of Lactobacillus
      paracasei ssp. paracasei YBJ01 (LPSP-YBJ01) isolated and identified from
      fermented yogurt. Strain LPSP-YBJ01 had stress tolerance against acidity, bile
      salt, and osmotic pressure. Five in vitro antioxidant assays were used to
      evaluate antioxidant activity of LPSP-YBJ01, which could scavenge free radicals
      (2,2-diphenyl-1-picrylhydrazyl and hydroxyl) and superoxide anion in vitro. In
      addition, strain LPSP-YBJ01 had stronger antilipid peroxidation activity and weak
      reducing power in vitro. We measured in vivo antioxidant activity of LPSP-YBJ01
      in an oxidation mouse model induced by d-galactose injection. Strain LPSP-YBJ01
      significantly increased serum superoxide dismutase (SOD), glutathione peroxidase,
      and total-antioxidant capability, and inhibited generation of malondialdehyde in
      a dose-dependent manner. In addition, strain LPSP-YBJ01 also increased the
      hepatic and splenic protein expressions of some antioxidant enzymes such as
      catalase, Cu/Zn-SOD, and Mn-SOD in mice treated with d-galactose. Thus, LPSP
      YBJ01 had antioxidant activity in vitro and in vivo and may be a useful
      probiotic.

PMID- 30292552
TI  - Is rumination time an indicator of methane production in dairy cows?
AB  - As long as large-scale recording of expensive-to-measure and labor-consuming
      traits, such as dry matter intake (DMI) and CH4 production (CH4P), continues to
      be challenging in practical conditions, alternative traits that are already
      routinely recorded in dairy herds should be investigated. An ideal indicator
      trait must, in addition to expressing genetic variation, have a strong
      correlation with the trait of interest. Our aim was to estimate individual level
      and phenotypic correlations between rumination time (RT), CH4P, and DMI to
      determine if RT could be used as an indicator trait for CH4P and DMI. Data from
      343 Danish Holstein cows were collected at the Danish Cattle Research Centre for
      a period of approximately 3 yr. The data set consisted of 14,890 records for DMI,
      15,835 for RT, and 6,693 for CH4P. Data were divided in primiparous cows only
      (PC) and all cows (MC), and then divided in lactation stage (early, mid, late,
      and whole lactation) to analyze the changes over lactation. Linear mixed models,
      including an animal effect but no pedigree, were used to estimate the
      correlations among traits. Phenotypic and individual level correlations between
      RT and both CH4P and DMI were close to zero, regardless of lactation stage and
      data set (PC or MC). However, CH4P and DMI were highly correlated, both across
      lactation stages and data sets. In conclusion, RT is unsuitable to be used as an
      indicator trait for either CH4P or DMI. Our study failed to validate RT as a
      useful indicator trait for both CH4P and DMI, but more studies with novel
      phenotypes can offer different approaches to select and incorporate important yet
      difficult to record traits into breeding goals and selection indexes.

PMID- 30292553
TI  - Invited review: Microbiota of the bovine udder: Contributing factors and
      potential implications for udder health and mastitis susceptibility.
AB  - Various body sites of vertebrates provide stable and nutrient-rich ecosystems for
      a diverse range of commensal, opportunistic, and pathogenic microorganisms to
      thrive. The collective genomes of these microbial symbionts (the microbiome)
      provide host animals with several advantages, including metabolism of
      indigestible carbohydrates, biosynthesis of vitamins, and modulation of innate
      and adaptive immune systems. In the context of the bovine udder, however, the
      relationship between cow and microbes has been traditionally viewed strictly from
      the perspective of host-pathogen interactions, with intramammary infections by
      mastitis pathogens triggering inflammatory responses (i.e., mastitis) that are
      often detrimental to mammary tissues and cow physiology. This traditional view
      has been challenged by recent metagenomic studies indicating that mammary
      secretions of clinically healthy quarters can harbor genomic markers of diverse
      bacterial groups, the vast majority of which have not been associated with
      mastitis. These observations have given rise to the concept of "commensal mammary
      microbiota," the ecological properties of which can have important implications
      for understanding the pathogenesis of mastitis and offer opportunities for
      development of novel prophylactic or therapeutic products (or both) as
      alternatives to antimicrobials. Studies conducted to date have suggested that an
      optimum diversity of mammary microbiota is associated with immune homeostasis,
      whereas the microbiota of mastitic quarters, or those with a history of mastitis,
      are considerably less diverse. Whether disruption of the diversity of udder
      microbiota (dysbiosis) has a role in determining mastitis susceptibility remains
      unknown. Moreover, little is known about contributions of various biotic and
      abiotic factors in shaping overall diversity of udder microbiota. This review
      summarizes current understanding of the microbiota within various niches of the
      udder and highlights the need to view the microbiota of the teat apex, teat
      canal, and mammary secretions as interconnected niches of a highly dynamic
      microbial ecosystem. In addition, host-associated factors, including
      physiological and anatomical parameters, as well as genetic traits that may
      affect the udder microbiota are briefly discussed. Finally, current understanding
      of the effect of antimicrobials on the composition of intramammary microbiota is
      discussed, highlighting the resilience of udder microbiota to exogenous
      perturbants.

PMID- 30292554
TI  - Immunoreactive properties of alpha-casein and kappa-casein: Ex vivo and in vivo
      studies.
AB  - The aim of this study was to evaluate the ex vivo and in vivo studies immune
      potential of alpha- and kappa-casein. Ex vivo, naive mouse splenocytes were
      stimulated with alpha- or kappa-casein. After 120 h of culture, the proliferation
      index (PI), determined by 3-(4,5 dimethylthiazol-2yl)-2,5-diphenyl tetrazolium
      bromide (MTT) assay and carboxyfluorescein diacetate N-succinimidyl ester (CFSE)
      staining, did not vary for either antigen, suggesting similar ex vivo immunogenic
      potential of both casein fractions. In vivo, BALB/ccmdb mice were sensitized with
      alpha- or kappa-casein and then gavaged with primary antigen. Mice immunized with
      alpha-casein had higher levels of IgG (216.33) and IgA (210.22) in serum at the
      end of the experiment compared with mice immunized with kappa-casein (215 and
      29.3 for IgG and IgA, respectively). The use of alpha-casein for mouse
      immunization and ex vivo lymphocyte stimulation resulted in higher concentrations
      of secreted cytokines (IL-4, IL-10) compared with kappa-casein stimulation. This
      is consistent with increasing regulatory T cell (Treg) lymphocyte populations,
      independent of the antigen used for stimulation. In summary, the immunogenic
      potential of alpha- and kappa-casein was similar. Humoral and cellular immune
      responses confirmed their strong, independent potential to induce B and T cells.
      We propose that the lymphocyte proliferation index be used as an initial
      screening for protein immunogenicity.

PMID- 30292555
TI  - Short communication: The effect of diarrhea and navel inflammation on the lying
      behavior of veal calves.
AB  - Many veal calves arrive to growing facilities with diseases, including diarrhea
      and navel inflammation. Observing neonatal calf behavior, such as lying behavior,
      can be used to better detect and determine the implications of these diseases.
      The aim of this study was to determine the effect of navel inflammation and
      diarrhea on lying behavior in neonatal veal calves. This study was part of a
      larger experiment that included a total of 360 male Holstein calves from 3
      cohorts; from these calves, we selected a subset of 125 calves (every third calf
      as they entered the barn) to be fitted with 3-dimensional accelerometers (Hobo
      Pendant G data loggers; Onset Computer Corp., Bourne, MA) on 1 hind leg to
      continuously measure lying time, number of lying bouts, and lying bout duration.
      Calves were housed individually on slatted flooring (Tenderfoot; Tandem Products
      Inc., Minneapolis, MN) in 3 rooms of a mechanically ventilated barn. Health exams
      were conducted twice weekly for 2 wk starting the day after arrival. Exams
      included rectal temperature, navel score (0 = normal, 1 = mildly inflamed, 2 =
      moderately inflamed, 3 = severely inflamed), and fecal score (0 = normal, 1 =
      semiformed, 2 = loose, 3 = watery). Calves were considered to have navel
      inflammation (n = 22) or diarrhea (n = 15) if they scored >=2 during at least 3
      of the 4 health exams. The lying behavior of these calves was compared with that
      of normal calves (n = 18) that had no signs of illness and rectal temperatures
      <39.4 degrees C during at least 3 of the 4 health exams. Data were analyzed using
      a repeated-measures ANOVA; models included cohort (1, 2, or 3), health status
      (normal, navel inflammation, or diarrhea), week (1 or 2), and a health by week
      interaction. There was an effect of health status on lying time, whereby normal
      calves spent more time lying compared with calves with inflamed navels and tended
      to spend more time lying compared with calves with diarrhea. There was no effect
      of health status on the number of lying bouts per day or on the duration of lying
      bouts. There were no health by week interactions. Results indicate that neonatal
      veal calves with navel inflammation and diarrhea may be less comfortable than
      calves without these conditions. Veal producers should consider adapting their
      facilities to create more comfortable lying environments to help calves better
      recover from disease, such as by adding a hospital pen with comfortable bedding.

PMID- 30292556
TI  - Effects of dry period energy intake on insulin resistance, metabolic adaptation,
      and production responses in transition dairy cows on grass silage-based diets.
AB  - High energy intake in the dry period has reportedly had adverse effects on
      mobilization of body reserves, dry matter intake, and productivity of dairy cows.
      We investigated whether grass silage (GS) fed ad libitum (high energy intake,
      HEI; 141% of daily metabolizable energy requirements) in an 8-wk dry period
      affects metabolic adaptation-specifically, peripheral insulin resistance-compared
      with a total mixed ration consisting of GS, wheat straw, and rapeseed meal
      (55/40/5%; controlled energy intake, CEI; 108% of metabolizable energy/d) fed ad
      libitum. Multiparous Ayrshire dairy cows (n = 16) were used in a randomized
      complete block design until 8 wk after parturition. Commercial concentrates were
      fed 1 and 2 kg/d during the last 10 to 6 and 5 to 0 d before the expected calving
      date, respectively. Postpartum, a similar lactation diet with ad libitum access
      to GS and increasing concentrate allowance (maximum of 16 kg/d) was offered to
      all. The HEI group gained more body weight and had higher plasma insulin,
      glucose, and beta-hydroxybutyrate concentrations than the CEI group prepartum.
      Postpartal plasma glucose tended to be higher and milk yield was greater from wk
      5 onward for HEI compared with CEI cows. An intravenous glucose tolerance test
      (IVGTT) was performed at -13 +/- 5 d and 9 +/- 1 d relative to calving. The HEI
      cows had greater insulin response to glucose load and smaller area under the
      response curve for glucose than CEI cows in prepartal IVGTT. Thus, compensatory
      insulin secretion adapted to changes in insulin sensitivity of the peripheral
      tissues, preserving glucose tolerance of HEI cows. Higher insulin levels were
      needed in HEI cows than in CEI cows to elicit a similar decrement of
      nonesterified fatty acid concentration in prepartal IVGTT, suggesting reduced
      inhibition of lipolysis by insulin in HEI cows before parturition. In conclusion,
      high energy intake of moderately digestible GS with low concentrate feeding in
      the close-up dry period did not have adverse effects on metabolic adaptation,
      insulin sensitivity, and body mobilization after parturition. Instead, this
      feeding regimen was more beneficial to early-lactation performance than GS-based
      total mixed ration diluted with wheat straw.

PMID- 30292557
TI  - Characteristics of diffusion-weighted images and apparent diffusion coefficients
      of ranulas and other masses in and around the floor of the mouth.
AB  - OBJECTIVE: The aim of this study was to evaluate the characteristics of diffusion
      weighted imaging (DWI) and apparent diffusion coefficient (ADC) values of
      ranulas. In addition, to elucidate DWI findings and ADC values of other
      representative masses in and around the floor of the mouth. STUDY DESIGN: DWI
      findings and ADC values in 35 patients with ranulas and 33 patients with other
      masses were retrospectively reviewed with a central focus on cystic masses or
      lesions that may have cyst-like components in and around the floor of the mouth
      based on the diagnosis of each respective disease. RESULTS: Ranulas were all well
      defined, homogeneous masses with high signal intensity on DWI. The mean +/-
      standard deviation ADC value of the 35 ranulas was 2.59 +/- 0.31 * 10-3 mm2/s.
      There was a significant difference in ADC values between simple and plunging
      ranulas. On DWI, most other masses were heterogeneous, and most ADC values,
      except those for thyroglossal duct cysts, hemangiomas, and pleomorphic adenomas,
      were significantly lower than those for ranulas. CONCLUSIONS: The characteristic
      DWI and ADC findings of ranulas can be determined accurately, and these data can
      be significantly useful in the differential diagnosis of many kinds of diseases
      in and around the oral floor.

PMID- 30292558
TI  - Evolving radiation therapy techniques for scalp angiosarcoma.

PMID- 30292559
TI  - Normalizing glucocorticoid levels attenuates metabolic and neuropathological
      symptoms in the R6/2 mouse model of huntington's disease.
AB  - Huntington's disease (HD) is a fatal genetic neurological disorder caused by a
      mutation in the human Huntingtin (HTT) gene. This mutation confers a toxic gain
      of function of the encoded mutant huntingtin (mHTT) protein, leading to
      widespread neuropathology including the formation of mHTT-positive inclusion
      bodies, gene dysregulation, reduced levels of adult dentate gyrus neurogenesis
      and neuron loss throughout many regions of the brain. Additionally, because HTT
      is ubiquitously expressed, several peripheral tissues are also affected. HD
      patients suffer from progressive motor, cognitive, psychiatric, and metabolic
      symptoms, including weight loss and skeletal muscle wasting. HD patients also
      show neuroendocrine changes including a robust, significant elevation in
      circulating levels of the glucocorticoid, cortisol. Previously, we confirmed that
      the R6/2 mouse model of HD exhibits elevated corticosterone (the rodent homolog
      of cortisol) levels and demonstrated that experimentally elevated corticosterone
      exacerbates R6/2 HD symptomology, resulting in severe and rapid weight loss and a
      shorter latency to death. Given that efficacious therapeutics are lacking for HD,
      here we investigated whether normalizing glucocorticoid levels could serve as a
      viable therapeutic approach for this disease. We tested the hypothesis that
      normalizing glucocorticoids to wild-type levels would ameliorate HD symptomology.
      Wild-type (WT) and transgenic R6/2 mice were allocated to three treatment groups:
      1) adrenalectomy with normalized, WT-level corticosterone replacement (10
      MUg/ml), 2) adrenalectomy with high HD-level corticosterone replacement (35
      MUg/ml), or 3) sham surgery with no corticosterone replacement. Normalizing
      corticosterone to WT levels led to an improvement in metabolic rate in male R6/2
      mice, as indicated by indirect calorimetry, including a reduction in oxygen
      consumption and normalization of respiratory exchange ratio values (p < .05 for
      both). Normalizing corticosterone also ameliorated brain atrophy in female R6/2
      mice and skeletal muscle wasting in both male and female R6/2 mice (p < .05 for
      all). Female R6/2 mice given WT-level corticosterone replacement also showed a
      reduction in HD neuropathological markers, including a reduction in mHTT
      inclusion burden in the striatum, cortex, and hippocampus (p < .05 for all). This
      data illustrates that ameliorating glucocorticoid dysregulation leads to a
      significant improvement in HD symptomology in the R6/2 mouse model and suggests
      that cortisol-reducing therapeutics may be of value in improving HD patient
      quality of life.

PMID- 30292560
TI  - Venomous Snakebites in Canada: A National Review of Patient Epidemiology and
      Antivenom Usage.
AB  - INTRODUCTION: There are 3 pit viper species in Canada. Limited Canadian
      literature exists on the epidemiology of venomous snakebites and the treatment
      patterns with antivenom. This study described the epidemiology, the utilization
      of antivenom, and estimated expenditures due to forfeited antivenom for pit viper
      envenomations in Canada. METHODS: A retrospective review of the Health Canada
      Special Access Program records to generate descriptive statistics. Data are
      presented as mean+/-SD (range), as appropriate. RESULTS: The geographic
      distribution of Canadian pit viper species is presented. There were 99
      envenomations reported in Canada from January 2009 to December 2015. The number
      of envenomations per year was 14+/-6 (6-21). CroFab and Antivipmyn are used in
      Canada to treat envenomations. The number of vials for patient treatment was 17+/
      12 (3-66) and 16+/-9 (6-42) for CroFab and Antivipmyn, respectively. Antivenom
      stock usage for patient treatment varied across the country with provincial means
      reported for British Columbia (33%), Alberta (37%), Saskatchewan (27%), and
      Ontario (71%). The costs incurred secondary to forfeited stock where estimated
      as: $1,280,000 USD in British Columbia, $255,000 in Alberta, $60,000 in
      Saskatchewan, and $0 in Ontario. CONCLUSIONS: The absolute number of annual
      envenomations is small and the 3 Crotalinae species are limited to relatively
      narrow geographic areas in British Columbia, Alberta, Saskatchewan, and Ontario.
      The utilization of antivenom in the treatment of patients revealed that regions
      where the western and prairie rattlesnake reside forfeited a substantial amount
      of antivenom from 2009 to 2015. Organizations responsible for maintaining
      antivenom supplies on a provincial or regional level could use these data to
      guide antidote stocking and reduce costs.

PMID- 30292562
TI  - NR3C2 Gene is Associated with Susceptibility to High-Altitude Pulmonary Edema in
      Han Chinese.
AB  - INTRODUCTION: The mineralocorticoid receptor is encoded by the NR3C2 gene and
      plays an important role in regulating vascular tone in high-altitude pulmonary
      edema (HAPE). This study aimed to investigate the association of the
      polymorphisms in the NR3C2 gene with HAPE susceptibility in Han Chinese. METHODS:
      We enrolled 133 HAPE patients and 131 matched healthy Han Chinese from the Yushu
      area in Qinghai, where the altitude is greater than 3500 m. Two single nucleotide
      polymorphisms (SNPs) of the NR3C2 gene, rs2070951 and rs5522, were genotyped by
      the Sequenom MassARRAY SNP assay. RESULTS: The genotypic distributions and allele
      frequencies of NR3C2 SNP rs5522 were significantly different between the HAPE and
      control groups (P<0.05). The frequency of the A allele of rs5522 was
      significantly higher in the HAPE group than in the control group (P<0.05) with an
      odds ratio of 1.7 (95% CI: 1.0-2.8). There were no significant differences in the
      genotypic distributions and allele frequencies of NR3C2 SNP rs2070951 between the
      HAPE and control groups. The frequencies of the C-A and C-G haplotypes were
      significantly higher in the HAPE group than in control group. CONCLUSIONS: The
      rs5522 polymorphism of the NR3C2 gene was associated with HAPE susceptibility in
      Chinese subjects. The A allele may contribute to the susceptibility to HAPE. The
      frequency of the C-A and C-G haplotypes of rs2070951 and rs5522 in the NR3C2 gene
      may increase the risk of HAPE.

PMID- 30292563
TI  - High Altitude Illness: Knowledge, Practice, and Attitudes of Porters in Nepal.
AB  - INTRODUCTION: Porters working at high altitude face a number of preventable
      health risks ranging from frostbite to potentially fatal high-altitude pulmonary
      and cerebral edema. Porters are often recruited from impoverished low-altitude
      areas, poorly equipped in terms of protective clothing, and tasked with carrying
      loads that equal or exceed their body mass to high elevations. Despite a large
      population of porters working throughout mountainous parts of the world, there is
      little documentation regarding knowledge levels, attitudes, and practices related
      to the prevention of altitude illness in this population. Much of the literature
      focuses on biomechanics of load carrying for porters or altitude issues for
      trekkers. METHODS: A cross-sectional survey was developed using a modified Delphi
      technique. The survey was administered to a convenience sample of porters (n=146)
      from diverse cultural groups between Lukla (2774 m) and Everest Base Camp (5361
      m). RESULTS: Many of the porters started at a young age, carried heavy loads, and
      had difficulty identifying symptoms of high altitude illness, and less than 20%
      correctly identified preventive measures for high-altitude illness. CONCLUSIONS:
      Porters in the Khumbu region continue to face hazards in their working
      environment. Future research and health education campaigns should address
      knowledge deficits and help with the design of tailored interventions.

PMID- 30292564
TI  - Discrimination of Pulmonary Nodule Volume Change for Low- and High-contrast Tasks
      in a Phantom CT Study with Low-dose Protocols.
AB  - RATIONALE AND OBJECTIVES: The quantitative assessment of volumetric CT for
      discriminating small changes in nodule size has been under-examined. This phantom
      study examined the effect of imaging protocol, nodule size, and measurement
      method on volume-based change discrimination across low and high object to
      background contrast tasks. MATERIALS AND METHODS: Eight spherical objects ranging
      in diameter from 5.0 mm to 5.75 mm and 8.0 mm to 8.75 mm with 0.25 mm increments
      were scanned within an anthropomorphic phantom with either foam-background (high
      contrast task, ~1000 HU object to background difference)) or gelatin-background
      (low-contrast task, ~50 to 100 HU difference). Ten repeat acquisitions were
      collected for each protocol with varying exposures, reconstructed slice
      thicknesses and reconstruction kernels. Volume measurements were obtained using a
      matched-filter approach (MF) and a publicly available 3D segmentation-based tool
      (SB). Discrimination of nodule sizes was assessed using the area under the ROC
      curve (AUC). RESULTS: Using a low-dose (1.3 mGy), thin-slice (<=1.5 mm) protocol,
      changes of 0.25 mm in diameter were detected with AU = 1.0 for all baseline sizes
      for the high-contrast task regardless of measurement method. For the more
      challenging low-contrast task and same protocol, MF detected changes of 0.25 mm
      from baseline sizes >=5.25 mm and volume changes >=9.4% with AUC>=0.81 whereas
      corresponding results for SB were poor (AUC within 0.49-0.60). Performance for SB
      was improved, but still inconsistent, when exposure was increased to 4.4 mGy.
      CONCLUSION: The reliable discrimination of small changes in pulmonary nodule size
      with low-dose, thin-slice CT protocols suitable for lung cancer screening was
      dependent on the inter-related effects of nodule to background contrast and
      measurement method.

PMID- 30292565
TI  - Dermal injuries caused by purse seine capture result in lasting physiological
      disturbances in coho salmon.
AB  - Fish vitality can be measured by classifying reflex impairments (i.e., a visual
      impression of the ability to respond to induced stimuli) and visible injuries.
      These metrics can predict survival probability following release from fisheries,
      and monitoring physiological disturbances following capture can help understand
      mechanisms of mortality. To test the hypothesis that severity of injury and
      reflex impairment influences the time course of physiological recovery, coho
      salmon (Oncorhynchus kisutch) were held for up to 84-h following capture by purse
      seine. We classified reflex impairments and visible dermal injuries, and through
      repeated blood sampling, assessed metrics indicative of stress, exhaustion, and
      osmoregulatory disturbances. Reflex-impairments and blood lactate levels
      suggested fish were exhausted upon capture but recovered after 48 h. Conversely,
      fish with dermal injuries showed disruptions to ion homeostasis that were greater
      in more severely injured fish and increased over time. While reflex impairments
      may predict short term post-release mortality, the prolonged physiological
      disturbances caused by dermal injuries are likely to be responsible for delayed
      mortality; our results suggest that disruptions to ion homeostasis is a possible
      mechanism of post-release mortality.

PMID- 30292566
TI  - Association between diastolic cardiac dysfunction and nonalcoholic fatty liver
      disease: A systematic review and meta-analysis.
AB  - BACKGROUND/OBJECTIVES: Recent studies have suggested an association between
      nonalcoholic fatty liver disease (NAFLD) and diastolic cardiac dysfunction,
      although the results were inconsistent. This study was conducted to investigate
      this possible association. METHODS: A comprehensive literature review was
      conducted utilizing the MEDLINE and Embase databases from inception through May
      2018 to identify all cross-sectional studies that compared the prevalence of
      diastolic cardiac dysfunction among patients with NAFLD to individuals without
      NAFLD. Effect estimates from each study were extracted and combined using the
      random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS:
      A total of 12 studies with 280,645 participants fulfilled the eligibility
      criteria and were included in the meta-analysis. There was a significant
      association between NAFLD and diastolic cardiac dysfunction with a pooled odds
      ratio (OR) of 2.02 (95% confidence interval (CI), 1.47-2.79; I2 89%). Subgroup
      analysis based on the country of origin continued to demonstrate a significant
      association in subgroups of both Western and Eastern countries with pooled ORs of
      1.76 (95% CI, 1.14-2.72; I2 85%) and 2.59 (95% CI, 1.42-4.69; I2 87%),
      respectively. Limitations included high between-study heterogeneity, lack of
      unified definition of diastolic dysfunction and presence of publication bias.
      CONCLUSIONS: A significant association between diastolic cardiac dysfunction and
      NAFLD was observed in this meta-analysis. This observation could suggest the need
      for careful cardiovascular surveillance among patients with NAFLD.

PMID- 30292567
TI  - Sex differences in psychomotor development during the preschool period: A
      longitudinal study of the effects of environmental factors and of emotional,
      behavioral, and social functioning.
AB  - We sought to determine the extent to which sex differences in psychomotor
      development during the preschool period can be explained by differential exposure
      to environmental factors and/or differences in emotional, behavioral, or social
      functioning. Children from the EDEN mother-child cohort were assessed for
      language, gross motor, and fine motor skills at 2, 3, and 5-6 years of age using
      parental questionnaires and neuropsychological tests. Structural equation models
      examining the associations between sex and language, gross motor, and fine motor
      skills at 2, 3, and 5-6 years were performed while adjusting for a broad range of
      pre- and postnatal environmental factors as well as emotional, behavioral and
      socialization difficulties. Girls (n = 492) showed better fine motor skills than
      boys (n = 563) at 2 years (Cohen's d = 0.67 in the fully adjusted models), at 3
      years (d = 0.72), and to a lesser extent at 5-6 years (d = 0.29). Girls also
      showed better language skills at 2 years (d = 0.36) and 3 years (d = 0.37) but
      not at 5-6 years (d = 0.04). We found no significant differences between girls
      and boys in gross motor skills at 2, 3, or 5-6 years. Similar results were found
      in the models unadjusted and adjusted for pre- and postnatal environmental
      factors as well as emotional, behavioral, and socialization difficulties. Our
      findings are consistent with the idea that sex differences in fine motor and
      language skills at 2 and 3 years of age are not explained by differential
      exposure to environmental factors or by sex differences in emotional, behavioral,
      or social functioning.

PMID- 30292568
TI  - A systematic assessment of socioeconomic status and executive functioning in
      early childhood.
AB  - Lower socioeconomic status (SES) consistently relates to poorer executive
      function (EF). This study used a systematic and nuanced approach to understand
      how SES relates to children's EF at a process level. We assessed children aged
      4.5-5.5 years. This is a key developmental period because EF is no longer a
      unitary construct but rather EF components statistically load on separate factors
      and index distinct aspects of EF. Children completed a working memory task that
      involved a cognitive load component and a go/no-go task to assess inhibitory
      control and vigilance. Accuracy and reaction time were assessed, and each task
      involved four blocks to assess performance over time. Lower SES related to lower
      accuracy for working memory, inhibitory control, and vigilance as well as slower
      reaction time for working memory. SES did not relate to go/no-go reaction time.
      For working memory, lower SES related to poorer accuracy on lower cognitive load
      trials, but there were no SES differences on higher cognitive load trials. SES
      did not relate to maintenance of performance over time. Results suggest that for
      this age group the majority of domains showed SES differences. However, there
      were no SES differences in performance for remembering two items and maintaining
      performance. Thus, although overall lower SES related to poorer EF performance,
      there were no SES effects for skills that are still emerging for all children,
      namely, maintaining task performance across time and remembering two items at
      once. Results highlight the importance of assessing EF as a multidimensional
      construct and may help to identify targets for intervention.

PMID- 30292569
TI  - Cheating behavior in children: Integrating gaze allocation and social awareness.
AB  - Children's cheating and factors supporting honesty are not well understood. The
      current work explored variables involved in children's cheating through eye
      tracking and an implicit manipulation in which extrinsic awareness of the effects
      of one's behaviors on others was primed. Participants played a computer game with
      the option for a monetary gain in which they could earn more if they selectively
      erred in response to more profitable stimuli. Results show that children cheat by
      making selective effort toward more profitable errors; however, extrinsic
      awareness inhibits these cheating behaviors. Importantly, gaze toward children's
      earnings mediates this relationship, suggesting that extrinsic awareness
      mitigates an impulsive looking pattern, which in turn results in less cheating.
      Findings suggest that an implicit manipulation, highlighting the potential
      implications of one's actions for others, seems to effectively suppress cheating
      among children. Furthermore, attention toward earnings offers a cognitive process
      that acts to mediate the effect of this manipulation on cheating. Taken together,
      this framework suggests psychoneurocognitive and social processes that influence
      cheating in children, offering a direction for future implicit intervention
      techniques to support honest performance.

PMID- 30292570
TI  - A Novel Morphological Analysis of DXA-DICOM Images by Artificial Neural Networks
      for Estimating Bone Mineral Density in Health and Disease.
AB  - One of the best methods for diagnosing bone disease in humans is site-specific
      and total bone mineral density (BMD) measurements by Dual-energy X-ray
      Absorptiometry (DXA) machines. The basic disadvantage of this technology is
      inconsistent BMD measurements among different DXA machines from different
      manufacturers due to different image analysis algorithms. The objective of the
      present study was to apply artificial neural networks (ANNs) to estimate total
      BMD for diagnosing a population of Egyptians with and without pathology, using
      extracted features from DXA-DICOM images based on the Histogram and Binary
      algorithms as compared to reference BMD measurements by DXA machine. The sample
      size comprised 3000 male and female participants with an age range 22-49years,
      who were referred to us for diagnosis and/or treatment and for DXA total body
      scans in the period from January 2016 till December 2017. We constructed an entry
      computer data-logging visible unit, where we applied morphological operations to
      get a specific bone image, and used their extracted feature vectors as inputs to
      ANNs with cascade training, gathering, and testing for DXA-DICOM image
      processing. The multilayer feed-forward ANN set up its initial weights, carried
      out training and initiated the recall mode, and finally observed its decision and
      interaction based on estimated BMD. The ANN construction was carried out using a
      3-layer architecture, with one hidden layer of 85 neurons. The input layer has
      neuron numbers equal to 256 for the Histogram and 77,365 for Binary algorithms,
      respectively. Total BMD estimation performance based on the Binary algorithm was
      capable of identifying all DXA-DICOM images with an accuracy of 100% for the
      training, cross-validation, and testing of the ANN phases. We believe this
      strategy will represent the means for standardizing bone measurements of all DXA
      machines, regardless of the manufacturer.

PMID- 30292571
TI  - Identification and expression of prostaglandin E synthase (PGES) gene in the
      central nervous system and ovary during ovarian maturation of the female mud
      crab, Scylla olivacea.
AB  - Prostaglandins have important physiological roles in marine invertebrates,
      including larval development and reproduction. The prostaglandin E concentration
      fluctuates during the ovarian development of crustaceans. The biosynthetic
      pathway of prostaglandin, however, has not been well studied in portunid crabs,
      including in the mud crab, Scylla olivacea. In this study, the aim was to
      investigate the presence of prostaglandin E synthase (PGES), enzyme that
      catalyzes the terminal conversion in the prostaglandin E2 (PGE2) biosynthesis,
      and its gene expression in the central nervous system (CNS) and ovary during
      ovarian maturation of S. olivacea. cDNA sequence encoding PGES was cloned from
      the S. olivacea ovary. The PGES transcript of S. olivacea (Scyol-PGES) consists
      of 1258 nucleotides, which encodes for 420 amino acid PGES protein precursor.
      Investigation of gene expression by RT-PCR indicated that Scyol-PGES was detected
      in all organs studied. Based on in situ hybridization, Scyol-PGES was detected in
      the I to III stages for oocyte development of Stage 3 of ovarian development, and
      in the CNS, including the various neuronal clusters of the brain. In the ventral
      nerve cord, the Scyol-PGES gene was expressed in the neurons within the
      subesophageal, thoracic and abdominal ganglia. The Scyol-PGES gene expression as
      indicated by relative abundance of mRNA in the Stage 4 of ovarian development was
      greater than that at Stages 1 to 3 of ovarian development. This is the first
      report on PGES in the mud crab, S. olivacea, and its gene expression suggested
      the involvement of PGES in the ovarian development of this species.

PMID- 30292572
TI  - In vitro developmental competence of horse embryos derived from oocytes with a
      different corona radiata cumulus-oocyte morphology.
AB  - The increase in demand for in vitro produced horse embryos is fostering the
      development of commercial laboratories for this purpose. Nevertheless, blastocyst
      production after intracytoplasmic sperm injection (ICSI) is still not as great as
      desired in most of these laboratories. In relation to horse oocyte
      classification, both expanded and compact cumulus-oocyte-complexes (COCs) are
      used for in vitro embryo production. The aim of this study was to compare in
      vitro embryo developmental capacity of COCs from horses including those with only
      the corona radiata, frequently collected after aspiration procedures. Horse
      oocytes were collected by follicular aspiration of abattoir-derived ovaries.
      After classification as expanded, compact or corona radiata COCs, these were in
      vitro matured, fertilized by ICSI and in vitro cultured for 7.5 days. Maturation
      rate, cleavage rate and morula/blastocyst rates were recorded. No significant
      differences (P > 0.05) were detected among groups in maturation rate. Cleavage
      rate was less (P < 0.05) for embryos derived from oocytes with a corona radiata
      as compared to compact-derived embryos, but embryo development after 7.5 days of
      culture was similar among groups (P > 0.05). In conclusion, even if embryos
      derived from oocytes with corona radiata had a lesser cleavage rate after ICSI,
      the developmental capacity was similar to embryos derived from oocytes with a
      compact and expanded cumulus morphology, indicating these can be an useful source
      of embryos in horses.

PMID- 30292573
TI  - How to implement directed acyclic graphs to reduce bias in addiction research.

PMID- 30292574
TI  - A systematic review into the incidence, severity and duration of antidepressant
      withdrawal effects: Are guidelines evidence-based?
AB  - INTRODUCTION: The U.K.'s current National Institute for Health and Care
      Excellence and the American Psychiatric Association's depression guidelines state
      that withdrawal reactions from antidepressants are 'self-limiting' (i.e.
      typically resolving between 1 and 2weeks). This systematic review assesses that
      claim. METHODS: A systematic literature review was undertaken to ascertain the
      incidence, severity and duration of antidepressant withdrawal reactions. We
      identified 24 relevant studies, with diverse methodologies and sample sizes.
      RESULTS: Withdrawal incidence rates from 14 studies ranged from 27% to 86% with a
      weighted average of 56%. Four large studies of severity produced a weighted
      average of 46% of those experiencing antidepressant withdrawal effects endorsing
      the most extreme severity rating on offer. Seven of the ten very diverse studies
      providing data on duration contradict the UK and USA withdrawal Guidelines in
      that they found that a significant proportion of people who experience withdrawal
      do so for more than two weeks, and that it is not uncommon for people to
      experience withdrawal for several months. The findings of the only four studies
      calculating mean duration were, for quite heterogeneous populations, 5days,
      10days, 43days and 79weeks. CONCLUSIONS: We recommend that U.K. and U.S.A.
      guidelines on antidepressant withdrawal be urgently updated as they are clearly
      at variance with the evidence on the incidence, severity and duration of
      antidepressant withdrawal, and are probably leading to the widespread
      misdiagnosing of withdrawal, the consequent lengthening of antidepressant use,
      much unnecessary antidepressant prescribing and higher rates of antidepressant
      prescriptions overall. We also recommend that prescribers fully inform patients
      about the possibility of withdrawal effects.

PMID- 30292575
TI  - The consequences of overcoming the human skin barrier by siloxanes (silicones)
      Part 1. Penetration and permeation depth study of cyclic methyl siloxanes.
AB  - Dynamic production of cyclic siloxanes: octamethylcyclotetrasiloxane D4,
      decamethylcyclopentasiloxane D5 and dodecamethylcyclohexasiloxane D6 increases
      their concentrations in environment. It is considered that both environmental
      pollution and the usage of personal care products and cosmetics containing cyclic
      siloxanes can be the main source of the human exposure by transdermal route. The
      aim of the study was to verify the possibility to overcome the skin barrier by
      cyclic siloxanes (ATR-FTIR and GC-FID), evaluation of diffusion pathway to
      stratum corneum SC (Fluorescence microscopy), and determination of depth of
      permeation to deeper skin layers: epidermis and dermis (ATR-FTIR) and also of
      potential interaction with SC lipids and proteins (Fluorescence microscopy, ATR
      FTIR) and the cytotoxicity studies against HaCaT cells (MTT test). The results
      show that D4, D5 and D5 can penetrate to SC and permeate into the deeper layers
      of the skin: epidermis and dermis. The quantitative analysis (GC-FID) showed that
      total cumulative doses for D4, D5 and D6 were: 42.50; 95.37 and 77.19 MUg/cm2/24
      h, respectively. The microscopic analysis proved, transepidermal route through
      the lipid matrix as well as through the canyons (intercluster spaces) were a
      diffusion pathway to the SC as well as disruption of human SC lipid structure by:
      D4 (the most), D5 and D6 (the least). The cytotoxicity studies demonstrated that
      the tested range of concentrations of D5 and D6 (up to 300 mM, 111 300 mg and 133
      500 mg respectively) did not impaired the HaCaT growth, while D4 had IC50 value
      of 40 098 mM +/- 7.94 (10 906 +/- 872,5 mg).

PMID- 30292576
TI  - UN High-Level Meeting to end tuberculosis disappointing.

PMID- 30292577
TI  - Department of Error.

PMID- 30292579
TI  - Enlarging the loop: closed-loop insulin delivery for type 1 diabetes.

PMID- 30292580
TI  - Corrigendum to 'Pre-operative Color Doppler Ultrasonography Predicts Endovenous
      Heat Induced Thrombosis After Endovenous Radiofrequency Ablation' [European
      Journal of Vascular & Endovascular Surgery 56/1 (2018) 94-100].

PMID- 30292581
TI  - Social support and chronic disease management among older adults of Mexican
      heritage: A U.S.-Mexico perspective.
AB  - This study explores the association between social support and chronic disease
      self-management among older adults of Mexican heritage who live in the U.S. and
      Mexico. We hypothesize that social support increases the ability to manage
      hypertension and Type 2 (T2) diabetes, regardless of place of residence. We also
      investigate if differences in country of residence and health system factors
      influence the ability to manage chronic conditions. Older adults 65 years or
      older from Los Angeles (LA) and Mexico City (CDMX), with diagnosed hypertension
      or T2 diabetes (self-reported), attending government agencies, participated in
      the study. The statistical analyses investigate differences between older adults
      in LA and CDMX; identify the association between social support and chronic
      disease self-management; and examine the role of T2 diabetes treatment, testing
      and complications on self-management. Our study findings show that social support
      was a statistically significant predictor of improved T2 diabetes self-management
      (37%-51%, p < 0.05). The association between social support and hypertension self
      management was only significant (90% confidence level) for adherence to weight
      management and increased alcohol consumption. Our study did not identify
      statistically significant differences in social support between LA and CDMX.
      However, almost 40% of sampled older adults were at risk of social isolation,
      signaling a vulnerable population that needs to be targeted by health and social
      systems in the U.S. and Mexico. Our study also shows that social support is a
      strong predictor of improved T2 diabetes management in the U.S. and Mexico. While
      older adults in the U.S. and Mexico reported similar access to care and health
      insurance coverage, higher adherence to low salt diets in LA and reduced coverage
      of glucose testing in CDMX could signal areas of opportunity for policymakers.
      Health care providers in both countries need to identify ways of improving
      adherence to physical activity and weight management.

PMID- 30292578
TI  - Closed-loop insulin delivery in suboptimally controlled type 1 diabetes: a
      multicentre, 12-week randomised trial.
AB  - BACKGROUND: The achievement of glycaemic control remains challenging for patients
      with type 1 diabetes. We assessed the effectiveness of day-and-night hybrid
      closed-loop insulin delivery compared with sensor-augmented pump therapy in
      people with suboptimally controlled type 1 diabetes aged 6 years and older.
      METHODS: In this open-label, multicentre, multinational, single-period, parallel
      randomised controlled trial, participants were recruited from diabetes outpatient
      clinics at four hospitals in the UK and two centres in the USA. We randomly
      assigned participants with type 1 diabetes aged 6 years and older treated with
      insulin pump and with suboptimal glycaemic control (glycated haemoglobin [HbA1c]
      7.5-10.0%) to receive either hybrid closed-loop therapy or sensor-augmented pump
      therapy over 12 weeks of free living. Training on study insulin pump and
      continuous glucose monitoring took place over a 4-week run-in period. Eligible
      subjects were randomly assigned using central randomisation software. Allocation
      to the two study groups was unblinded, and randomisation was stratified within
      centre by low (<8.5%) or high (>=8.5%) HbA1c. The primary endpoint was the
      proportion of time that glucose concentration was within the target range of 3.9
      10.0 mmol/L at 12 weeks post randomisation. Analyses of primary outcome and
      safety measures were done in all randomised patients. The trial is registered
      with ClinicalTrials.gov, number NCT02523131, and is closed to accrual. FINDINGS:
      From May 12, 2016, to Nov 17, 2017, 114 individuals were screened, and 86
      eligible patients were randomly assigned to receive hybrid closed-loop therapy
      (n=46) or sensor-augmented pump therapy (n=40; control group). The proportion of
      time that glucose concentration was within the target range was significantly
      higher in the closed-loop group (65%, SD 8) compared with the control group (54%,
      SD 9; mean difference in change 10.8 percentage points, 95% CI 8.2 to 13.5;
      p<0.0001). In the closed-loop group, HbA1c was reduced from a screening value of
      8.3% (SD 0.6) to 8.0% (SD 0.6) after the 4-week run-in, and to 7.4% (SD 0.6)
      after the 12-week intervention period. In the control group, the HbA1c values
      were 8.2% (SD 0.5) at screening, 7.8% (SD 0.6) after run-in, and 7.7% (SD 0.5)
      after intervention; reductions in HbA1c percentages were significantly greater in
      the closed-loop group compared with the control group (mean difference in change
      0.36%, 95% CI 0.19 to 0.53; p<0.0001). The time spent with glucose concentrations
      below 3.9 mmol/L (mean difference in change -0.83 percentage points, -1.40 to 
      0.16; p=0.0013) and above 10.0 mmol/L (mean difference in change -10.3 percentage
      points, -13.2 to -7.5; p<0.0001) was shorter in the closed-loop group than the
      control group. The coefficient of variation of sensor-measured glucose was not
      different between interventions (mean difference in change -0.4%, 95% CI -1.4% to
      0.7%; p=0.50). Similarly, total daily insulin dose was not different (mean
      difference in change 0.031 U/kg per day, 95% CI -0.005 to 0.067; p=0.09) and
      bodyweight did not differ (mean difference in change 0.68 kg, 95% CI -0.34 to
      1.69; p=0.19). No severe hypoglycaemia occurred. One diabetic ketoacidosis
      occurred in the closed-loop group due to infusion set failure. Two participants
      in each study group had significant hyperglycaemia, and there were 13 other
      adverse events in the closed-loop group and three in the control group.
      INTERPRETATION: Hybrid closed-loop insulin delivery improves glucose control
      while reducing the risk of hypoglycaemia across a wide age range in patients with
      suboptimally controlled type 1 diabetes. FUNDING: JDRF, NIHR, and Wellcome Trust.

PMID- 30292582
TI  - Prevalence of liver steatosis and its relation to liver function tests and lipid
      profile in patients at medical check-up.
AB  - INTRODUCTION AND AIMS: Nonalcoholic fatty liver disease has now become a
      worldwide health problem, and its dramatic increase is due to the prevalence of
      diseases such as obesity, type 2 diabetes mellitus, and metabolic syndrome. The
      aim of our study was to publish the current prevalence of liver steatosis in a
      Mexican population undergoing routine medical check-up, as well as to analyze its
      relation to BMI, liver function tests, and lipid profile. MATERIALS AND METHODS:
      An observational, retrospective, cross-sectional study was conducted on patients
      that underwent medical check-up within the time frame of January 2011 and
      December 2015 at the Hospital San Javier. Patients included in the study were
      those with somatometry measurements (BMI), lipid profile, liver function tests,
      and abdominal ultrasound with a multi-frequency convex transducer. RESULTS: We
      found that 65% of the patients presented with overweight or obesity and there was
      a 49.19% prevalence of liver steatosis in the study population. That prevalence
      was more frequent in men and liver steatosis was strongly linked to an increase
      in triglycerides, AST, and GGT and a decrease in HDL. CONCLUSIONS: Establishing
      the technical aspects of the study was an important aid to having better
      correlation with and standardization of the accepted definitions, given that
      ultrasound is an adequate screening technique for an open population. Our results
      clearly showed a direct relation between liver steatosis and alterations in BMI,
      triglycerides, HDL, ALT, and GGT.

PMID- 30292583
TI  - Dietary management and supplementation with branched-chain amino acids in
      cirrhosis of the liver.
AB  - One of the most important characteristics of malnutrition is the loss of muscle
      mass and the severe depletion of the protein reserve, secondarily affecting
      energy metabolism. That impacts nutritional status and the progression of disease
      related complications. Nutritional treatment is one of the main factors in the
      comprehensive management of those patients. Achieving adequate energy intake that
      provides the macronutrients and micronutrients necessary to prevent or correct
      malnutrition is attempted through dietary measures. ESPEN, the European Society
      for Clinical Nutrition and Metabolism, recommends a caloric intake of 30
      40kcal/kg/day, in which carbohydrates provide 45-60% of the daily energy intake
      and proteins supply 1.0-1.5g/kg/day. The remaining portion of the total energy
      expenditure should be covered by lipids. The administration of branched-chain
      amino acids has been shown to be beneficial not only in counteracting
      malnutrition, but also as a coadjuvant treatment in specific complications, thus
      playing a favorable role in outcome and quality of life. Therefore, branched
      chain amino acids should be considered part of nutritional treatment in patients
      with advanced stages of cirrhosis of the liver, particularly in the presence of
      complications.

PMID- 30292585
TI  - Purinergic Signaling: A New Pharmacological Target Against Viruses?
AB  - Viral diseases represent a major global problem in human health, with high
      morbidity and mortality. Despite recent progress in antiviral treatments, several
      viral diseases are still not controlled and millions suffer from them every year.
      It has recently emerged that purinergic signaling participates in viral infection
      and replication. Furthermore, stimulation of purinergic receptors in infected
      cells also induces inflammatory and antiviral responses, thus contributing to the
      host antiviral defense. Here we review the multiple roles played by the
      purinergic signaling network in cell-virus interactions that can lead either to
      viral maintenance in the cells or, by contrast, to stronger antiviral responses,
      and discuss potential future applications of purinergic signaling modulation for
      the treatment of viral diseases.

PMID- 30292586
TI  - Pyrus pyrifolia fruit peel as sustainable source for spherical and porous network
      based nanocellulose synthesis via one-pot hydrolysis system.
AB  - In the present study, we attempted revalorization of pear (Pyrus pyrifolia L.)
      peel residue into high value-added nanomaterials. A green and facile one-pot
      isolation procedure was designed to simplify the isolation process of
      nanocellulose directly from pear peel residue. The one-pot approach employed in
      this work is interesting as the reaction involved less harmful chemicals usage
      and non-multiple steps. The reaction was carried out by adding hydrogen peroxide
      as an oxidant and chromium (III) nitrate as catalyst in the acidic medium under
      mild process conditions. FTIR spectroscopy proved that the pear peel derived
      nanocellulose was purely cellulose phases without the presence of non-cellulosic
      layer. XRD study indicated that the isolated nanocellulose possessed of cellulose
      I polymorph with high crystallinity index of 85.7%. FESEM analysis clearly
      revealed that the considerable size reduction during one-pot process. Remarkably,
      TEM analysis revealed that the isolated nanocellulose consisted of network-liked
      nature and spherical shaped morphologies with high aspect ratio of 24.6. TGA
      showed nanocellulose has lower thermal stability compared to pear peel residue.
      This study provided a cost-effective method and straightforward one-pot process
      for fabrication of nanocellulose from pear peel residue. This is the first
      investigation on the nanocellulose extraction from pear fruit.

PMID- 30292584
TI  - Prevalence of eosinophilic esophagitis: A multicenter study on a pediatric
      population evaluated at thirty-six Latin American gastroenterology centers.
AB  - INTRODUCTION AND OBJECTIVE: Eosinophilic esophagitis is a chronic, immune
      mediated disease described in case series and publications worldwide. Over the
      past twenty years, the authors of different studies have attempted to evaluate
      its incidence and prevalence. The objetive of the present study was to estimate
      the prevalence of eosinophilic esophagitis in a group of children seen at 36
      pediatric gastroenterology centers in ten Latin American countries. MATERIALS AND
      METHODS: A multicenter, observational, and cross-sectional study was conducted
      that estimated the period prevalence of eosinophilic esophagitis in children seen
      at outpatient consultation and that underwent diagnostic upper gastrointestinal
      endoscopy for any indication at 36 centers in 10 Latin American countries, within
      a 3-month time frame. RESULTS: Between April and June 2016, 108 cases of
      eosinophilic esophagitis were evaluated. Likewise, an average of 29,253
      outpatient consultations and 4,152 diagnostic upper gastrointestinal endoscopies
      were carried out at the 36 participating centers. The period prevalence of
      eosinophilic esophagitis in the population studied (n=29,253) was 3.69
      cases*1,000 (95% CI: 3.04 to 4.44), and among the children that underwent routine
      upper gastrointestinal endoscopy (n=4,152), it was 26x1,000 (95% CI: 22.6 to
      29.4). CONCLUSIONS: The general period prevalence of eosinophilic esophagitis in
      a group of children evaluated at 36 Latin American pediatric gastroenterology
      centers was 3.69*1,000, and in the children that underwent endoscopy, it was
      26*1,000. There was important prevalence variability between the participating
      countries and centers. The present analysis is the first study conducted on the
      prevalence of pediatric eosinophilic esophagitis in Latin America.

PMID- 30292587
TI  - Effect of zero-valent iron/starch nanoparticle on nitrate removal using MD
      simulation.
AB  - In this study, the efficacy of zero-valent iron nanostructure modified by starch
      for removal of nitrate was investigated. Effect of zero-valent iron/starch
      nanoparticle in the presence of Thiobacillus dinitrificans for removal of nitrate
      was simulated via material studio software. Thermodynamic principles and proper
      equations were used via molecular dynamic (MD) simulation. The results of
      software predictions were demonstrated by radial distribution function (RDF),
      density, potential energy and temperature graphs. According to the graphs, the
      simultaneous in the presence of zero-valent iron/starch nanoparticle and
      Thiobacillus dinitrificans increase the removal efficiency of nitrate reached 91%
      and in the absence of nanoparticle was 44.44%.

PMID- 30292588
TI  - Intramedullary nailing of forearm shaft fractures by biodegradable compared with
      titanium nails: Results of a prospective randomized trial in children with at
      least two years of follow-up.
AB  - There are disadvantages in Elastic Stable Intramedullary Nailing (ESIN) of
      forearm-shaft fractures, such as the need of implant removal. Biodegradable
      Intramedullary Nailing (BIN) is a new technique developed for these fractures. We
      hypothesized that there is no difference in rotational ROM between the patients
      treated by BIN vs. ESIN. A randomized, controlled clinical trial included
      patients, aged 5-15 years, requiring surgery for forearm-shaft fractures.
      Biodegradable polylactide-co-glycolide (PLGA) nails (Activa IM-NailTM, Bioretec
      Ltd., Finland) were used in 19 and titanium nails (TEN(r), SynthesDePuy Ltd.,
      USA) in 16 patients. Rotational ROM of forearm after two years was the primary
      outcome. Elbow and wrist ROM, pain and radiographic bone healing were secondary
      outcomes. Forearm rotation was mean 162 degrees  and 151 degrees  in BIN and ESIN
      groups, respectively (P = 0.201). No difference between the groups was found in
      any other ROMs. Three cases in the ESIN vs. none in the BIN group reported pain
      (P = 0.113). There was no clinically significant residual angulation in
      radiographs. Two adolescents in the BIN group vs. none in the ESIN (P = 0.245)
      were excluded because of implant failure; another two with complete bone union
      suffered from re-injury. Therefore, satisfactory implant stability among older
      children needs to be studied.

PMID- 30292589
TI  - Lixisenatide and renal outcomes in patients with type 2 diabetes and acute
      coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo
      controlled trial.
AB  - BACKGROUND: The results of the ELIXA trial demonstrated the cardiovascular safety
      of lixisenatide, a short-acting glucagon-like peptide-1 receptor agonist, in
      patients with type 2 diabetes and acute coronary syndrome. In this exploratory
      analysis of ELIXA, we investigate the effect of lixisenatide on renal outcomes.
      METHODS: ELIXA was a randomised, double-blind, placebo-controlled trial, done at
      828 sites in 49 countries. Patients with type 2 diabetes and a recent coronary
      artery event were randomly assigned (1:1) to a daily subcutaneous injection of
      lixisenatide (10-20 MUg) or volume-matched placebo, in addition to usual care,
      until at least 844 patients had an adjudicated major adverse cardiovascular event
      included in the primary outcome. Patients, study staff, and individuals involved
      in analysis of trial data were masked to treatment assignment. The primary and
      secondary endpoints of this trial have been reported previously. Here, in an
      exploratory analysis of ELIXA, we investigated percentage change in urinary
      albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate
      (eGFR) according to prespecified albuminuria status at baseline (normoalbuminuria
      [UACR <30 mg/g]; microalbuminuria [>=30 to <=300 mg/g]; and macroalbuminuria
      [>300 mg/g]) using a mixed-effect model with repeated measures. Time to new-onset
      macroalbuminuria and doubling of serum creatinine were also assessed with Cox
      proportional hazards models. The ELIXA trial is registered with
      ClinicalTrials.gov, number NCT01147250, and is completed. FINDINGS: Of 6068
      patients randomly allocated between July 9, 2010, and Aug 2, 2013, baseline UACR
      data were available for 5978 (99%). Median follow-up time was 108 weeks. 4441
      (74%; 2191 assigned to placebo and 2250 assigned to lixisenatide) had
      normoalbuminuria, 1148 (19%; 596 assigned to placebo and 552 assigned to
      lixisenatide) had microalbuminuria, and 389 (7%; 207 assigned to placebo and 182
      assigned to lixisenatide) had macroalbuminuria. After 108 weeks, the placebo
      adjusted least-squares mean percentage change in UACR from baseline with
      lixisenatide was -1.69% (95% CI -11.69 to 8.30; p=0.7398) in patients with
      normoalbuminuria, -21.10% (-42.25 to 0.04; p=0.0502) in patients with
      microalbuminuria, and -39.18% (-68.53 to -9.84; p=0.0070) in patients with
      macroalbuminuria. Lixisenatide was associated with a reduced risk of new-onset
      macroalbuminuria compared with placebo when adjusted for baseline HbA1c (hazard
      ratio [HR] 0.808 [95% CI 0.660 to 0.991; p=0.0404]) or baseline and on-trial
      HbA1c (HR 0.815 [0.665 to 0.999; p=0.0491]); point estimates were similar when
      adjusted for other traditional renal risk factors. At week 108, the largest eGFR
      decline from baseline was observed in the macroalbuminuric group, but no
      significant differences were observed between the two treatment groups. No
      significant differences in eGFR decline were identified between treatment groups
      in any UACR subgroup. In the trial safety population, doubling of serum
      creatinine occurred in 35 (1%) of 3032 patients in the placebo group and 41 (1%)
      of 3031 patients in the lixisenatide group (HR 1.163, 95% CI 0.741-1.825;
      p=0.5127). As previously reported in the ELIXA trial, the proportion of patients
      with renal adverse events was low (48 [1.6%] of 3032 patients in the placebo
      group vs 48 [1.6%] of 3031 patients in the lixisenatide group) and did not
      significantly differ between treatment groups. INTERPRETATION: Lixisenatide
      reduces progression of UACR in macroalbuminuric patients, and is associated with
      a lower risk of new-onset macroalbuminuria after adjustment for baseline and on
      trial HbA1c and other traditional renal risk factors. FUNDING: Sanofi.

PMID- 30292590
TI  - Glucose lowering and the kidney: are all drug classes equal?

PMID- 30292591
TI  - Early and Delayed Meniscal Shrinkage After Fresh-Frozen Lateral Meniscal
      Allograft Transplantation: Magnetic Resonance Imaging Study With a Midterm Follow
      up.
AB  - PURPOSE: To evaluate whether fresh-frozen meniscal allograft shrinkage occurs
      only during the first year of the early remodeling period or progresses over the
      delayed period of midterm years and to determine whether these changes were
      associated with certain clinical and radiologic outcomes. METHODS: We
      retrospectively reviewed meniscal allograft transplantations (MATs) performed by
      1 senior surgeon (S-I.B.) using fresh-frozen allograft from 2008 to 2013. The
      inclusion criteria were the patients who had midterm follow-up magnetic resonance
      imaging (MRI) scans between 3 and 6 years after isolated lateral MATs. We
      excluded the graft tears found on the 1-year or midterm MRI scans. MATs were
      indicated for the treatment persistent compartmental pain in young to middle
      aged, physically active patients who had well-aligned nonarthritic joint without
      ligament insufficiency. The meniscal width of the transplants at the midbody and
      posterior horn was measured on day 2 (as a reference), at 1 year (after early
      remodeling period), and after 3 to 6 years (delayed period) postoperatively.
      Joint space width changes during each interval were measured on 45 degrees 
      flexion posteroanterior views. The Lysholm score and Tegner activity scale were
      used to evaluate clinical outcomes. RESULTS: Eighty-four isolated lateral MATs
      with the midterm MRI scans were identified. Of these, 17 graft tears were found;
      therefore, we analyzed 67 patients (32 male and 35 female patients) with a mean
      age of 30.9 years (range, 15-52 years). The mean relative meniscal width at the
      midbody decreased to 93.7% (95% confidence interval [CI], 91.8%-95.6%; P < .001)
      at 1 year postoperatively and to 88.0% (95% CI, 85.6%-90.3%; P < .001) at the
      midterm follow-up of 4.0 +/- 1.0 years. The posterior horn shrank less than the
      midbody during the same period (96.0%; 95% CI, 94.8%-97.1%) at 1 year (P < .001)
      and 92.5% (95% CI, 91.0%-94.1%) at the last follow-up (P < .001). Although there
      was no severe shrinkage (>50% of the initial size), the incidence of moderate
      (25%-50%) changes at the midbody increased from 1 (1.5%) at 1 year to 5 (7.5%) at
      the last follow-up, respectively. We could not find any significant positive
      correlations between the relative meniscal width and patient-reported outcomes or
      joint space width changes after 1 year or at the last follow-up. CONCLUSIONS:
      Shrinkage of fresh-frozen meniscal transplants occurred during both the early
      remodeling and delayed midterm periods. Although the changes were greater in the
      midbody than in the posterior horn, the overall changes were less than those of
      the previous studies using cryopreserved grafts. We could not find that the
      meniscal shrinkage over the midterm period were significantly associated with
      inferior outcomes in this series. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 30292592
TI  - Prognostic Factors of Arthroscopic Debridement for Central Triangular
      Fibrocartilage Complex Tears in Adults Younger Than 45 Years: A Retrospective
      Case Series Analysis.
AB  - PURPOSE: The purpose of this study was to analyze factors that affect the
      treatment outcomes of arthroscopic debridement for central triangular
      fibrocartilage complex (TFCC) lesions in adults <45 years of age. METHODS: A
      total of 71 patients (mean age, 39 years; range, 20-44 years) who had been
      arthroscopically diagnosed with central TFCC tears were treated with arthroscopic
      debridement. Demographic, clinical, and arthroscopic findings were examined and
      analyzed. The response to treatment, including pain numeric rating scale on an
      ulnar provocation test; Disability of the Arm, Shoulder, and Hand score; and
      satisfaction with treatment, was assessed at 12-month follow-up. RESULTS: The
      mean pain numeric rating scale (6.6 +/- 3.6 to 2.4 +/- 2.0, P < .01) and
      Disability of the Arm, Shoulder, and Hand (59.3 +/- 15.0 to 33.7 +/- 14.1, P <
      .01) scores exhibited significant clinical improvement at 12-month follow-up. In
      terms of satisfaction, 43 patients (70.5%) were satisfied (enthusiastic or
      satisfied) and 18 (29.5%) were dissatisfied (noncommittal or disappointed). In
      the satisfied group, there were 24 flap and 19 wearing tears, whereas in the
      dissatisfied group, there were 4 flap and 14 wearing tears (P = .02). The extent
      of ulnar plus variance on preoperative radiographs also differed between the 2
      groups (0.5 +/- 1.2 vs 1.7 +/- 1.1, P < .01). There were no significant
      differences in age, gender, hand dominance, or work level between the groups.
      After controlling for confounding variables, the wearing type tears (odds ratio,
      3.4) and greater ulnar plus variance (odds ratio, 2.0) were associated with a
      higher likelihood of dissatisfaction after arthroscopic TFCC debridement.
      CONCLUSIONS: Although clinical outcome scores showed significant improvement
      after arthroscopic debridement for central TFCC tears, wearing type tears and
      greater ulnar plus variance were associated with dissatisfaction and poorer
      postoperative outcomes after the procedure. LEVEL OF EVIDENCE: Level IV, case
      series.

PMID- 30292593
TI  - Arthroscopic Double-Layer Lasso Loop Technique to Repair Delaminated Rotator Cuff
      Tears.
AB  - PURPOSE: To evaluate the arthroscopic double-layer lasso loop repair technique
      for delaminated posterosuperior rotator cuff tears. METHODS: Forty-one patients
      underwent arthroscopic rotator cuff repair of a delaminated posterosuperior
      rotator cuff tear by the double-layer lasso loop technique. Their preoperative
      and postoperative clinical and functional scores were compared to evaluate
      surgical outcomes. The prerequisite for inclusion was a minimum follow-up period
      of 2 years. We excluded patients with a history of shoulder surgery before the
      double-layer lasso loop repair. RESULTS: Statistically significant improvements
      (P < .001) were found in the Constant score (54 vs 83) and University of
      California, Los Angeles functional score (6.4 vs 9.5). Pain and strength improved
      according to the Jobe test, bear-hug test, belly-press test, Gerber lift-off
      test, and external rotation test (P < .001). No significant difference in
      strength was noted between the operated and nonoperated sides. There was only 1
      complete rerupture (3.1%), whereas 5 patients (15.6%) had partial ruptures.
      CONCLUSIONS: The arthroscopic double-layer lasso loop repair technique for
      delaminated posterosuperior rotator cuff tears is an effective procedure. Our
      series showed a low rerupture rate. At a mean follow-up of 44 months,
      postoperative recovery with resultant functional, pain, and patient satisfaction
      scores was good to excellent and was comparable with the nonoperated side. LEVEL
      OF EVIDENCE: Level IV, case series.

PMID- 30292594
TI  - Revision Anterior Cruciate Ligament Reconstruction With Hamstrings and Extra
      articular Tenodesis: A Mid- to Long-Term Clinical and Radiological Study.
AB  - PURPOSE: To present the mid- to long-term clinical and radiographic outcomes of a
      series of patients who underwent revision anterior cruciate ligament (ACL)
      reconstruction with doubled gracilis and semitendinosus (DGST) autograft and a
      lateral extra-articular tenodesis (LET). METHODS: Patients who underwent revision
      ACL reconstruction with DGST and LET by a single surgeon between January 1997 and
      December 2013 were included. Revision was indicated by ACL failure noted on
      magnetic resonance imaging, persistent clinical instability, or laxity on
      clinical exam. Patients were evaluated preoperatively and at latest follow-up by
      an independent board-certified orthopaedic surgeon. Outcomes included Lachman and
      pivot shift tests, validated clinical and patient reported outcomes scores, and
      radiographic analysis. The presence of previous meniscectomy or chondral injury
      was recorded intraoperatively. RESULTS: A total of 118/132 potential patients
      (89.4%) was available for follow-up at a mean 10.6 years (3-19 years)
      postoperatively. Lachman and pivot shift examinations as well as the side-to-side
      difference on an KT-1000 arthrometer demonstrated significant improvement at
      latest follow-up (P < .05) versus preoperative evaluation. Severe degenerative
      disease was present in 25% of patients on radiograph and correlated with worsened
      clinical outcomes. Previous meniscectomy was the only risk factor analyzed that
      correlated with worsened radiographic grade. No patients had a graft tear based
      on clinical and/or magnetic resonance imaging evaluation, but 9 (7.6%) failed
      based on a side-to-side difference of >5 mm on the KT-1000, a grade >=2+ on pivot
      shift, or report of continued instability. CONCLUSIONS: Revision ACL
      reconstruction with DGST and LET at mid- to long-term follow-up provides
      continued improvement in clinical and radiological outcomes from preoperative
      assessment. Meniscectomy was the only factor related to worsened radiological
      grades and clinical outcomes. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 30292595
TI  - Predictive Factors for and Detection of Lateral Hinge Fractures Following Open
      Wedge High Tibial Osteotomy: Plain Radiography Versus Computed Tomography.
AB  - PURPOSE: To compare the accuracy of plain radiography and computed tomography
      (CT) in detecting lateral hinge fractures and to identify predictive factors of
      the lateral hinge fractures after open wedge high tibial osteotomy (HTO).
      METHODS: This study included patients who underwent isolated primary open wedge
      HTO for medial compartment degenerative arthritis from 2015 to 2016 and were
      evaluated by postoperative CT scans and followed for a minimum of 1 year. This
      study involved 48 patients (48 knees) undergoing open wedge HTO for primary
      medial osteoarthritis. Lateral hinge fractures were evaluated on immediate plain
      radiographs and CT scans according to the Takeuchi classification. Predictive
      factors of plain radiograph-based hinge fracture and CT-based hinge fracture were
      investigated. RESULTS: The detection rate of lateral hinge fracture was
      significantly higher on CT scans than on plain radiographs (50% vs 14.6%; P <
      .001). Seven knees (14.6%) showed lateral hinge fractures on postoperative plain
      radiographs, including 6 with type I and 1 with type III fractures; 24 (50.0%)
      showed lateral hinge fractures on postoperative CT scans, including 20 with type
      I, 2 with type II, and 2 with type III fractures. CT scans detected 14 type I, 2
      type II, and 1 type III hinge fractures not detected by plain radiographs. The
      medial opening gap width was the only predictor of lateral hinge fracture on CT
      scans (adjusted odds ratio, 1.565; P =.034). CONCLUSIONS: The incidence of
      lateral hinge fracture of the knee after open wedge HTO was higher on CT scans
      than on plain radiographs. The medial opening gap width was the only predictor of
      lateral hinge fractures, suggesting a need for care when spreading the gap to
      avoid lateral hinge fractures. LEVEL OF EVIDENCE: Level III, cross-sectional
      study.

PMID- 30292596
TI  - Biomechanical Analysis of Single-, Double-, and Triple-Bundle Configurations for
      Coracoclavicular Ligament Reconstruction Using Cortical Fixation Buttons With
      Suture Tapes: A Cadaveric Study.
AB  - PURPOSE: To compare the acromioclavicular (AC) joint stability of single-bundle
      (SB), double-bundle with an anterolateral limb (DBa), double-bundle with a
      posterolateral limb (DBp), and triple-bundle (TB) coracoclavicular (CC) ligament
      reconstructions using cortical fixation buttons with suture tapes. METHODS: Eight
      cadaveric shoulders were used. AC joint translation and rotational stability were
      tested for intact and following 4 different CC reconstruction techniques: SB,
      DBa, DBp, and TB configurations using cortical fixation buttons with suture
      tapes. For each reconstruction and native AC joint as control, anteroposterior
      (AP) and superoinferior translations were quantified using 10- and 15-N
      translational loads and anterior and posterior rotations were measured using 0.16
      and 0.32-Nm rotational torque. RESULTS: DBp reconstruction showed significantly
      better AP stability compared with SB and DBa reconstruction at 10 and 15 N (DBp:
      4.1 +/- 0.6 mm, SB: 7.8 +/- 1.1 mm, P < .001; DBa: 6.5 +/- 0.7 mm, P = .02 at 10
      N; DBp: 5.5 +/- 0.8 mm, SB: 10.1 +/- 1.0 mm, P = .003; DBa: 9.1 +/- 0.7 mm, P =
      .02 at 15 N). The degree of total rotation showed tendency to decrease according
      to increasing number of bundles; however, there were no significant differences
      (SB: 43.1 +/- 9.2 degrees , DBa: 37.9 +/- 7.3 degrees , DBp: 33.9 +/- 6.8 degrees
      , TB: 32.2 +/- 6.6 degrees , P = .37 at 0.32 Nm). CONCLUSIONS: An additional
      posterolateral clavicular hole for CC ligament reconstruction using cortical
      fixation buttons with suture tapes resulted in better AP stability compared with
      SB reconstruction, whereas use of additional anterolateral clavicular hole did
      not show any improvement compared with SB reconstruction. Reconstruction using
      both anterolateral and posterolateral clavicular holes did not guarantee better
      stability compared with SB reconstruction. There was an increasing tendency of
      rotational stability with number of bundle increases, although they did not reach
      statistical difference. CLINICAL RELEVANCE: When surgeons consider double-bundle
      CC ligament reconstruction using cortical fixation buttons with suture tapes, it
      is better to position the lateral clavicular hole posteriorly to restore AP
      stability.

PMID- 30292597
TI  - Remplissage Using Interconnected Knotless Anchors: Superior Biomechanical
      Properties to a Knotted Technique?
AB  - PURPOSE: To evaluate the biomechanical fixation strength and gap formation of 2
      different remplissage fixation methods (double pulley knotted construct and
      interconnected knotless repair construct) in cadaver specimens. METHODS: Seven
      matched pairs of human cadaveric shoulders were used for testing (mean age, 56 +/
      10 years). A shoulder from each matched pair was randomly selected to receive a
      Hill-Sachs remplissage using either a knotted (No. 2 FiberWire double pulley with
      3.0-mm SutureTak anchors) or knotless (coreless No. 2 FiberWire interconnected
      between 3.9-mm knotless CorkScrew anchors) double mattress construct. The tendon
      was cycled between 10 and 100 N at 1 Hz for 100 cycles, followed by a single
      cycle pull to failure at 33 mm/s. Cyclic displacement, load to clinical failure
      (5 mm), yield load, and mode of failure were recorded. RESULTS: Neither construct
      demonstrated clinical failure under cyclic loading. Load to clinical failure was
      higher for the knotless repair than that of the knotted repair (788 +/- 162 N vs
      488 +/- 227 N; P = .003). The yield load was higher for the knotless repair than
      that of the knotted repair (1,080 +/- 298 N vs 591 +/- 265 N; P = .008). The most
      common failure mode for the knotted repair was knot failure or tendon tearing,
      whereas the failure mode for the knotless repair was by anchor pull-out or tendon
      tear with no failures occurring via the interconnected suture construct
      mechanism. CONCLUSIONS: In this biomechanical study comparing cyclic and ultimate
      loading for 2 double mattress remplissage repairs, the construct using
      interconnected, knotless sutures outperformed the knotted construct. No failure
      of the interconnected suture construct mechanism by slippage or breakage was
      observed in the knotless group. CLINICAL RELEVANCE: The use of the interconnected
      knotless suture technique might improve the biomechanical strength of
      arthroscopic remplissage repairs in treating shoulder instability.

PMID- 30292598
TI  - Does hip center location affect the recovery of abductor moment after total hip
      arthroplasty?
AB  - BACKGROUND: In total hip arthroplasty (THA), placing the cup in an anatomic
      position is not always possible in case of deformities related to developmental
      dysplasia of the hip (DDH). Thus far, the influence of a hip center on the
      abductor moment after THA has not been clearly elucidated. Therefore, we
      performed a retrospective study to assess (1) how abductor muscle moment recovers
      postoperatively in THA and (2) whether acetabular cup position affects the
      recovery of abductor moment. HYPOTHESIS: A high hip center affects the recovery
      of abductor moment of a dysplastic hip after THA. PATIENTS AND METHODS: We
      evaluated 100 patients, who underwent unilateral primary THA, at 12 months
      postoperatively. The study included 86 women and 14 men, with a mean age of
      65.5+/-9.9 years (range, 40 to 86 years). Patients with secondary osteoarthritis
      due to DDH were included (Crowe 1: 76; Crowe 2: 15, Crowe 3:9, and Crowe 4:
      none). A cementless straight stem was implanted in all hips. Hip abductor moment
      was measured using a belt-stabilized hand-held dynamometer. The ratio of moment
      of the affected side to that of the contralateral side was calculated as moment
      ratio. The horizontal and vertical centers of rotation (H-COR and V-COR) (with
      respect to the inter teardrop line) and vertical shift (V-shift) (difference in V
      COR between the affected hip and the contralateral normal hip) were determined.
      RESULTS: At 6 and 12 months postoperatively, the abductor moment ratios were 95.1
      and 94.7%, respectively. Significant negative correlation was observed between
      the postoperative abductor moment ratio and V-COR at 6 months postoperatively (r=
      0.2436, p=0.0238). Significant delay in the recovery of abductor moment ratio was
      observed in the groups with higher hip center (V-shift>15mm) (odds ratio=12.7;
      95% CI: 2.11-232.1, p=0.0034) at 6 months postoperatively, which was fully
      recovered at 12 months postoperatively. DISCUSSION: Superior placement of a hip
      center, more than 15mm above the true hip center, delayed the recovery of
      abductor muscle moment after THA. LEVEL OF EVIDENCE: III, retrospective
      comparative study.

PMID- 30292599
TI  - Editorial.

PMID- 30292600
TI  - Mindfulness for Healthcare Providers: The Role of Non-Reactivity in Reducing
      Stress.
AB  - CONTEXT: There is strong evidence in the literature that the cultivation of
      mindfulness through programs such as Mindfulness-Based Stress Reduction (MBSR)
      has a profound impact on perceived stress for healthcare providers. The mechanism
      of the latter association is still being studied. However, it has been
      hypothesized that in particular, the cultivation of non-reactivity as a
      mindfulness skill may be particularly associated with the salutary effect of MBSR
      to reduce stress in health care providers even if adjusted for the benefit on
      quality of life gained after MBSR. The latter may represent important mechanistic
      information to build customized mindfulness interventions for health care
      providers. OBJECTIVE: Determine whether the change in non-reactivity to inner
      experience after MBSR is associated with the adjusted changes in perceived stress
      after MBSR. DESIGN: a Cross-sectional study. SETTING: A large, Midwestern
      teaching hospital. PARTICIPANTS: 100 health care providers. INTERVENTION: 8-week
      standard MBSR course. MAIN OUTCOME MEASURES: Perceived Stress Scale-10, Linear
      Analog Scale Assessment to measure Quality of life, and the mindfulness domain
      non-reactivity to inner experience was assessed by the non-reactivity subscale of
      the Five Facet Mindfulness Questionnaire. All measures were administered at
      baseline and completion of the intervention. RESULTS: The change from baseline to
      completion of MBSR was significant for all variables, with moderate-to-robust
      effect sizes. There was a significant negative correlation between non-reactivity
      and perceived stress both at baseline (p < 0.0001) and when comparing changes in
      scores from baseline to post-intervention (p < 0.0001). Change in non-reactivity
      to inner experience was robustly associated with the change in perceived stress
      (p < 0.0001) after MBSR (97% in 5000 bootstrapped models). CONCLUSION: Non
      reactivity to inner experience is a key aspect of MBSR that is independently
      associated with a change in perceived stress in health care providers.

PMID- 30292601
TI  - The association between diabetes and thoracic aortic aneurysms.
AB  - OBJECTIVE: The negative correlation between diabetes mellitus (DM) and abdominal
      aortic aneurysms (AAAs) is well described. The etiologic similarities and
      differences between AAAs and thoracic aortic aneurysms (TAAs) have also been
      documented. We aimed to evaluate the relationship between DM and TAA by
      performing a meta-analysis of contemporary clinical studies. METHODS: A
      systematic search of the literature was performed in accordance with the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to
      investigate the relationship of DM and TAA. Data from population cohort and case
      control studies were extracted and computed together to determine a pooled
      unadjusted odds ratio (OR) with corresponding 95% confidence intervals (CIs)
      using random-effects meta-analysis. RESULTS: Five population cohort studies and
      five case-control studies involving 1,006,360 patients met eligibility
      requirement and were included. Unadjusted pooled analysis of all 10 studies
      demonstrated an inverse association of DM with TAA (OR, 0.77; 95% CI, 0.61-0.98).
      Primary analysis of the five cohort studies demonstrated a statistically
      significant negative association between DM and TAA (OR, 0.70; 95% CI, 0.59
      0.84). However, primary analysis of the five case-control studies demonstrated a
      negative association between DM and TAA (OR, 0.86; 95% CI, 0.50-1.47) with no
      statistical significance. CONCLUSIONS: This meta-analysis demonstrated a
      statistically significant inverse association between DM and TAA, similar to that
      of AAA. Further research is required into the potentially protective mechanisms
      that DM may confer and whether there is biologic plausibility to exploit these
      mechanisms further to prevent aneurysm expansion and rupture.

PMID- 30292602
TI  - Not all lightweight lead aprons and thyroid shields are alike.
AB  - OBJECTIVE: With the explosion of minimally invasive surgery, the use of
      fluoroscopy has significantly increased. Concurrently, there has been a demand
      for lighter weight aprons. The industry answered this call with the development
      of lightweight aprons. Our goal was to see whether lighter weight garments
      provide reduced protection. METHODS: Dry laboratory testing was performed in a
      standard X-ray room, using a standard fluoroscopy table and standard acrylic
      blocks. A commercial-grade pressurized ion chamber survey meter (Ludlum Model
      9DP; Ludlum Measurements, Inc, Sweetwater, Tex) was used to detect gamma rays and
      X-rays above 25 keV. Nonlead aprons from several manufacturers were tested for
      scatter radiation penetration above the table at a fixed distance (3 feet) and
      compared with two standard 0.5-mm lead aprons of different manufacturers.
      RESULTS: Scatter measurements were made at 60 kVp and 70 kVp for pure lead (0.5
      mm), mixed, and nonlead protective garments. Scatter penetration for the nonlead
      blends and barium aprons was 292% and 258%, respectively, at 60 kVp compared with
      the pure lead apron. At the higher beam quality of 70 kVp, the scatter
      penetration was 214% and 233% for the blend and barium aprons, respectively,
      compared with the pure lead apron. Our measurements demonstrate a noticeable
      difference in scatter reduction between pure lead and nonlead garments. Pure
      barium aprons and nonlead aprons from certain companies demonstrated scatter
      penetration that is inconsistent with the 0.5 mm of lead equivalence as claimed
      on the label. In addition, there was an incidental finding of a handful of
      lightweight aprons with significant tears along the seams, leaving large gaps in
      protection. Our study also demonstrates that several companies rate their
      lightweight garments as 0.5 mm lead equivalent, when actually only a small area
      on the chest and abdomen where the garment overlapped was 0.5 mm, leaving the
      rest of the garment with half the protection at 0.25 mm. CONCLUSIONS: Our
      reliance on protective lead garments to shield us from the biologic effects of
      radiation exposure and the inferiority of some lightweight garments necessitate a
      streamlining of the testing methods and transparency in data reporting by
      manufacturers.

PMID- 30292603
TI  - Open staged repair of splenic and extensive superior mesenteric artery aneurysms.
AB  - A 31-year-old man with a history of multiple strokes of unknown etiology
      presented with multiple asymptomatic visceral artery aneurysms including a 3.3-cm
      bilobed splenic artery aneurysm and a 3.1-cm fusiform superior mesenteric artery
      aneurysm. He had no family history of aneurysms, and there was no evidence of
      collagen disease. He underwent open splenic artery aneurysm resection without
      splenectomy and had an uneventful recovery. Seven months later, he had open
      repair of his 14.6-cm-long fusiform superior mesenteric artery aneurysm with a 15
      cm-long collagen-coated polyester interposition graft with multiple visceral
      branch reimplantations into the graft. The postoperative course was uneventful,
      and computed tomography confirmed patent graft and side branches. Two years
      later, the patient remained free of abdominal symptoms, although he suffered
      another episode of a mild stroke.

PMID- 30292604
TI  - Outcomes and cost of fenestrated versus standard endovascular repair of intact
      abdominal aortic aneurysm in the United States.
AB  - BACKGROUND: Fenestrated endovascular aneurysm repair (FEVAR) has expanded the
      indications of this minimally invasive procedure to include patients with
      pararenal aneurysms. The actual cost of this relatively newer technology compared
      with standard endovascular aneurysm repair (EVAR) has not been studied before.
      Thus, the aim of this study was to analyze in-hospital costs and adverse outcomes
      in patients undergoing FEVAR vs EVAR for intact abdominal aortic aneurysms
      (AAAs). METHODS: Using the Premier Healthcare Database (2012-2015), we identified
      all patients who underwent elective EVAR and FEVAR. Univariable (chi2 test,
      Student t-test, median test) and multivariable (logistic regression and
      generalized linear modeling) analyses were implemented to examine in-hospital
      cost and adverse outcomes adjusting for patients' demographics, comorbidities,
      and regional characteristics. RESULTS: A total of 17,689 elective endovascular
      AAA repairs were performed; 1641 patients underwent FEVAR (9%), and the remaining
      16,048 patients underwent standard EVAR (91%). Patients undergoing FEVAR were
      more likely to be white (86.3% vs 84.3%; P = .03). Both groups had similar
      comorbidities except for cerebrovascular disease, which was higher among patients
      undergoing FEVAR (8.4% vs 6.7%; P = .01). The total length of hospital stay was
      slightly higher in patients undergoing FEVAR compared with EVAR (mean [standard
      deviation], 2.40 [3.39] days vs 2.23 [3.10] days; P = .03). The rates of any
      complication (11.3% vs 9.6%), renal injury (5.8% vs 4.3%), and neurologic injury
      (0.7% vs 0.4%) were significantly higher in the FEVAR group (all P < .05). No
      differences were seen in mortality (0.8% vs 0.5%) or cardiac (4.9% vs 4.4%),
      pulmonary (2.4% vs 2.2%), and bowel (1.5% vs 1.2%) complications between the two
      groups (all P > .05). In multivariable logistic regression analysis, FEVAR was
      associated with 40% increased odds of renal failure (odds ratio, 1.40; 95%
      confidence interval [CI], 1.11-1.76; P = .004) and 91% increased odds of
      neurologic injury (odds ratio, 1.91; 95% CI, 1.02-3.57; P = .04). The median
      total cost of the treatment was also significantly higher among patients
      undergoing FEVAR ($28,227 vs $26,781; P < .001). After adjustment, generalized
      linear modeling analysis showed that the cost of FEVAR was on average $1612
      higher than the cost of EVAR (adjusted cost, $1612; 95% CI, $1123-$2101; P <
      .001). CONCLUSIONS: In this large cohort of elective endovascular AAA repairs,
      compared with standard EVAR, FEVAR is associated with significantly increased
      odds of renal and neurologic injury. In addition, despite adjusting for patients'
      demographics, comorbidities, and major complications, total cost of FEVAR was
      significantly higher compared with standard EVAR. This is likely driven by the
      additional cost of fenestrated endografts and by the increased rate of
      complications related to FEVAR.

PMID- 30292605
TI  - Long-term outcomes after pediatric peripheral revascularization secondary to
      trauma at an urban level I center.
AB  - OBJECTIVE: The purpose of this investigation was to determine our limb-related
      contemporary pediatric revascularization perioperative and follow-up outcomes
      after major blunt and penetrating trauma. METHODS: A retrospective review was
      performed of a prospectively maintained pediatric trauma database spanning
      January 2010 to December 2017 to capture all level I trauma activations that
      resulted in a peripheral arterial revascularization procedure. All preoperative,
      intraoperative, and postoperative continuous variables are reported as a mean +/-
      standard deviation; categorical variables are reported as a percentage of the
      population of interest. RESULTS: During the study period, 1399 level I trauma
      activations occurred at a large-volume, urban children's hospital. The vascular
      surgery service was consulted in 2.6% (n = 36) of these cases for suspected
      vascular injury based on imaging or physical examination. Our study population
      included only patients who received an arterial revascularization, which was
      performed in 23 of the 36 consultations (1.6% of total traumas; median age, 11
      years). These injuries were localized to the upper extremity in 60.9% (n = 14),
      lower extremity in 30.4% (n = 7), and neck in 8.7% (n = 2). The mean Injury
      Severity Score in the revascularized cohort was 14.0 (+/-7.6). Bone fractures
      were associated with 39.1% of the vascular injuries (90% of blunt injuries).
      Restoration of in-line flow was achieved by an endovascular solution in one
      patient and open surgery in the remainder, consisting of arterial bypass in 59.1%
      and direct repair in 40.9%. Within 30 days of the operation, we observed no
      deaths, no infections of the arterial reconstruction, and no major amputations.
      One patient required perioperative reintervention by the vascular team secondary
      to the development of a superficial seroma without evidence of graft involvement.
      Mean follow-up in our cohort was 43.3 (+/-35.4) months. During this phase, no
      additional deaths, amputations, chronic wounds, or limb length discrepancies were
      observed. All vascular repairs were patent, and all but one patient reported
      normal function of the affected limb at the latest clinic visit. CONCLUSIONS:
      Traumatic peripheral vascular injury is rare in the pediatric population but is
      often observed secondary to a penetrating force or after long bone fracture.
      However, contemporary perioperative and long-term outcomes after surgical
      revascularization are excellent as demonstrated in this institutional case
      series.

PMID- 30292606
TI  - Contemporary outcomes of thoracofemoral bypass.
AB  - OBJECTIVE: Thoracofemoral bypass (TFB) is an alternative to aortofemoral bypass
      (AFB) or extra-anatomic bypass for severe aortoiliac occlusive disease (AIOD).
      TFB may be particularly useful in select patients with concurrent visceral aortic
      branch vessel disease, infrarenal aortic occlusions, or after failed AFB.
      However, there are few contemporary series describing the indications and
      outcomes for TFB. Therefore, the purpose of this analysis was to review our
      experience with TFB. METHODS: All patients undergoing TFB for occlusive disease
      from 2002 to 2017 were reviewed. All patients underwent left
      thoracoretroperitoneal exposure of the supraceliac aorta with division of the
      diaphragmatic crus and supraceliac cross-clamping. An end-to-side aortic
      anastomosis was created and each graft limb was tunneled in the retroperitoneum
      to the femoral bifurcation. Adjunctive visceral/infrainguinal revascularization
      was performed selectively based on symptoms, end-organ function, and/or
      preoperative imaging. The primary end points were major complications and 30-day
      mortality. Secondary end points included limb patency, freedom from major adverse
      limb events, and survival. Kaplan-Meier methodology was used to characterize the
      end points. RESULTS: Forty-one patients (age 61 +/- 9 years; 54% female; 7% in a
      hypercoaguable state) underwent TFB. The mean preoperative ankle-brachial index
      was 0.4 bilaterally. Indications included critical limb ischemia (56%),
      claudication (30%), acute limb ischemia (7%), and combined AIOD and mesenteric
      ischemia (7%). Seven patients (17%) had previously undergone AFB and 15 (38%) had
      previously undergone any prior aortic operation. Adjunctive visceral bypass
      occurred in 8 patients (20%; N = 14 grafts, n = 6 renal, n = 5 superior
      mesenteric artery, and n = 3 celiac). The postoperative duration of stay was 11
      days (interquartile range [IQR], 7-16 days) and the 30-day mortality was 5% (n =
      2). Major complications occurred in 34% of patients (N = 14; pulmonary, 15%;
      cardiac, 12%; bleeding, 7%; accidental splenectomy, 5%; renal, 5%; wound, 2%).
      The mean postoperative ankle-brachial index was 0.9 bilaterally. At a median
      follow-up of 7 months (IQR, 1-17 months), 5 patients (12%) underwent some form of
      reintervention (graft/limb related, n = 4 [n = 2 graft thrombosis, n = 2 graft
      infection], n = 1 mesenteric bypass revision). The estimated 3-year primary limb
      patency and freedom from major adverse limb events were 80 +/- 10%, and 70 +/-
      10%, respectively. The estimated 5-year survival was 93 +/- 5% (median, 27.3;
      IQR, 14.5-35.2; 95% confidence interval, 17.9-32.8). CONCLUSIONS: This experience
      represents one of the largest and most current series of retroperitoneal TFB. We
      demonstrate that TFB can be performed with good outcomes for patients with severe
      AIOD, especially if concomitant visceral/infrainguinal reconstruction is
      warranted. These results support a continued role for TFB in select patients.

PMID- 30292607
TI  - Open versus endovascular treatment of subclavian artery atherosclerotic disease.
AB  - OBJECTIVE: The aim of this study was to compare open and endovascular treatment
      of patients with subclavian artery atherosclerotic disease (SAAD) as far as early
      and late outcomes are concerned. METHODS: A systematic literature review
      conforming to established criteria was conducted to identify eligible articles
      published before January 2018. The following online search engines were used:
      PubMed, Embase, Scopus, and Cochrane Library (search conducted between December
      2017 and January 2018). Eligible studies compared early and late major outcomes
      between open and endovascular therapy for patients suffering from SAAD. RESULTS:
      Overall, seven clinical studies included 731 patients undergoing 760 procedures
      in total (297 endovascular and 463 open procedures). The majority of procedures
      (99.7%) referred to symptomatic patients, and more patients undergoing open
      surgery had an occlusion compared with patients undergoing endovascular repair,
      the majority of whom had a stenosis. Regarding early outcomes (30-day death,
      cardiac events, technical success, and central nervous system events), there was
      no difference between the two methods. Only peripheral nervous system
      complications were more prevalent in patients undergoing open repair (odds ratio
      [OR], 7.01; 95% confidence interval [CI], 2.142-22.921; P = .001). Regarding late
      outcomes, open repair was associated with significantly higher 1-year (OR, 4.33;
      95% CI, 1.954-9.619; P = .0003), 3-year (OR, 5.67; 95% CI, 2.881-11.167; P <
      .0001), and 5-year (OR, 4.27; 95% CI, 1.906-9.567; P = .0004) primary patency
      rates compared with endovascular therapy. However, 5-year freedom from recurrent
      symptoms as well as 5-year overall survival showed no difference. CONCLUSIONS:
      Open repair and endovascular repair in patients with SAAD do not show any
      difference concerning the majority of early major outcomes, although more
      patients undergoing open repair had an occlusion. However, open surgery seems to
      prevail regarding long-term primary patency, although long-term survival and
      freedom from recurrent symptoms show no difference.

PMID- 30292608
TI  - Near-instant noninvasive optical imaging of tissue perfusion for vascular
      assessment.
AB  - BACKGROUND: Noninvasive vascular tests are critical for identifying patients who
      may benefit from surgical revascularization, but current tests have significant
      limitations in people with diabetes. This study aimed to evaluate the ability of
      spatial frequency domain imaging (SFDI), an optical imaging method capable of
      measuring tissue oxygen saturation (StO2) and tissue hemoglobin, to assess lower
      extremity blood supply. METHODS: Ankle-brachial index, toe-brachial index, pedal
      Doppler waveforms, and SFDI images were prospectively evaluated in 47 consecutive
      patients with and without diabetes in whom there was concern for peripheral
      artery disease (PAD). SFDI is a noncontact optical imaging technology that uses
      structured illumination to quantify subsurface (2-3 mm in depth) StO2 and tissue
      hemoglobin in the dermal microcirculation (HbT1) and macrocirculation (HbT2) over
      a large field of view (15 * 20 cm) within 10 seconds. RESULTS: This demonstrates
      the ability of SFDI to capture reliable clinical measurements of perfusion in
      plantar aspects of the feet. SFDI StO2 values differentiate nondiabetic patients
      with and without arterial disease, defined as ankle-brachial index <0.9 (P =
      .06), but are limited in those with diabetes (P = .43). An elevated StO2 and
      reduced HbT1 are observed in people with diabetes compared with nondiabetic
      patients (P < .05). An SFDI-derived HbT2/HbT1 index differentiates diabetics with
      PAD vs no PAD (P < .01) using toe-brachial index <0.7 as a cutoff for PAD in
      diabetes. CONCLUSIONS: SFDI is a feasible, rapid, and easy to use widefield
      measurement of perfusion in a clinical setting. This first-of-use study suggests
      that the technology has potential to evaluate lower extremity perfusion in people
      with and without diabetes. Further studies with increased numbers of patients and
      end points including wound healing will need to be designed to fully evaluate the
      applicability of this new technology.

PMID- 30292609
TI  - Impact of routine completion angiography on outcome after carotid endarterectomy.
AB  - OBJECTIVE: The objective of this study was to analyze the impact of completion
      digital subtraction angiography (cDSA) after carotid endarterectomy (CEA) on
      technical and early clinical results. METHODS: This retrospective study included
      consecutive patients undergoing CEA from January 2011 to January 2015. Routine
      cDSA was performed in all patients. Study end points were the incidence of
      pathologic findings on completion angiography necessitating intraoperative
      revision, type of revision, periprocedural stroke rate, mortality, morbidity, and
      recurrent stenosis rate during follow-up (median, 5 months; range, 0-39 months).
      RESULTS: There were 827 procedures performed in 770 patients (male, 72.5%; median
      age, 70.6 years) with extracranial internal carotid artery (ICA) stenosis
      (asymptomatic, 57.3%); 426 patients underwent conventional endarterectomy (cCEA)
      with patch angioplasty (51.6%), 393 patients (47.5%) received an eversion
      technique (eCEA), and 8 patients (1%) underwent other revascularization.
      Immediate surgical revision based on angiographic findings after CEA was
      performed in 6.9% (57/827) of cases. Reasons for revision of the ICA were mural
      thrombus in 7.0% (4/57), dissections in 7.0% (4/57), residual stenosis in 8.7%
      (5/57), and intimal flaps of ICA in 1.8% (1/57). In six cases, combined
      pathologic changes of the ICA and external carotid artery led to revision. Thirty
      five revisions (4.2%) were performed for isolated pathologic angiographic
      findings of the external carotid artery; in two cases, revision was performed for
      residual stenosis of the common carotid artery. There was no significant
      difference regarding the frequency of revision between surgical techniques (cCEA,
      56.4%; eCEA, 63.6%; P = .76). However, mural thrombus as a reason for revision
      was more common in the cCEA group; plaque residues were more common in the eCEA
      group. Periprocedural (30-day) stroke rate was 0.5% (4/827); six additional
      patients suffered transient ischemic attack (0.7%). The mortality rate within 30
      days was 0.1% (1/827); 30-day morbidity was 4.2% (35/827). The rate of recurrent
      stenosis (>50%) during follow-up was 0.8%. There was no significant correlation
      between pathologic findings on cDSA with consecutive revision and perioperative
      stroke rate, recurrent stenosis rate, mortality, or morbidity. CONCLUSIONS: In
      this study, cDSA after CEA detected findings leading to immediate intraoperative
      surgical revision in a relevant proportion of cases. Therefore, cDSA represents a
      reasonable quality control without being associated with significantly prolonged
      operating times. Whether cDSA reduces perioperative stroke rate, procedure
      related mortality, morbidity, or incidence of early recurrent stenosis cannot be
      proven with the current study design.

PMID- 30292610
TI  - Increased hospital costs are associated with low skeletal muscle mass in patients
      undergoing elective open aortic surgery.
AB  - OBJECTIVE: Low psoas muscle area is shown to be an indicator for worse
      postoperative outcome in patients undergoing vascular surgical. Additionally, it
      has been associated with longer durations of hospital stay in patients with
      cancer who undergo surgery and subsequently greater health care costs in Europe
      and the United States. We sought to evaluate this effect on hospital expenditure
      for patients undergoing vascular repair in a health care system with universal
      access. METHODS: Skeletal muscle mass was assessed on preoperative abdominal
      computed tomography scans of patients undergoing open aortic aneurysm repair in a
      retrospective fashion. The skeletal muscle index (SMI) was used to define low
      muscle mass. Health care costs were obtained for all patients and the
      relationship between a low SMI and higher costs was explored using linear
      regression and cross-sectional analysis. RESULTS: We included 156 patients (81.5%
      male) with a median age of 72 years undergoing elective surgery for infrarenal
      abdominal aortic aneurysm in this analysis. The median SMI for patients with low
      skeletal muscle mass was 53.21 cm2/kg and for patients without, 70.07 cm2/kg.
      Hospital duration of stay was 2 days longer in patients with low skeletal muscle
      mass as compared with patients with normal (14 days vs 11 days; P = .001), as was
      duration of intensive care stay (3 days vs 1 day; P = .01). The median overall
      hospital costs were ?10,460 higher for patients with a low SMI as compared with
      patients with a normal physical constitution (?53,739 [interquartile range,
      ?45,007-?62,471] vs ?43,279 [interquartile range, ?39,509-?47,049]; P = .001).
      After confounder adjustment, a low SMI was associated with a 14.68% cost increase
      in overall hospital costs, for a cost increase of ?6521. CONCLUSIONS: Low
      skeletal muscle mass is independently associated with higher hospital as well as
      intensive care costs in patients undergoing elective aortic aneurysm repair.
      Strategies to reduce this risk factor are warranted for these patients.

PMID- 30292611
TI  - Metabolic syndrome is associated with increased cardiac morbidity after
      infrainguinal bypass surgery irrespective of the use of cardiovascular risk
      modifying agents.
AB  - BACKGROUND: The burden of metabolic syndrome (MetS) is increasing in the United
      States and is pervasive among patients with peripheral arterial disease. Whereas
      MetS has been implicated in the development of all types of cardiovascular
      disease and adverse outcomes after vascular interventions, little is known about
      how MetS influences perioperative outcomes of lower extremity bypass surgery and
      whether any negative effects can be modified by use of cardiovascular risk
      modifying medications. METHODS: We used the National Surgical Quality Improvement
      Program vascular procedure-targeted database to capture patients undergoing
      infrainguinal bypass surgery between 2011 and 2015. We defined MetS using the
      modified MetS criteria: concomitant diabetes, hypertension, and body mass index
      >30 kg/m2. We used multivariable logistic regression analyses to examine the
      association between MetS and 30-day postoperative morbidity and mortality. We
      also examined whether preoperative aspirin, statin, and beta blockade modify the
      effects of MetS on 30-day postoperative outcomes. RESULTS: Of 10,053 patients who
      underwent infrainguinal bypass, 16% (1693) met criteria for MetS. After adjusting
      for covariates, MetS was significantly (P <= .05) associated with higher odds of
      postoperative myocardial infarction (odds ratio [OR], 1.66), infection (OR,
      1.76), renal dysfunction (OR, 2.42), and length of stay (0.34 days). Within the
      MetS subgroup, there were no significant associations between use of preoperative
      cardiovascular risk-modifying agents and postoperative outcomes, with the
      exception of beta blockade and an increase in length of stay (0.33 days).
      CONCLUSIONS: Patients with MetS undergoing infrainguinal bypass surgery are at an
      increased risk of postoperative complications, including myocardial infarction.
      This elevated risk persists despite medical therapy with preoperative aspirin,
      statin, and beta blockade.

PMID- 30292612
TI  - Aortoiliac calcification correlates with 5-year survival after abdominal aortic
      aneurysm repair.
AB  - BACKGROUND: An anatomic severity grade (ASG) score to categorize and to define
      anatomic factors for abdominal aortic aneurysm (AAA) repair was proposed. Other
      studies have previously reported that aortic anatomic complexity is a marker of
      survival and resource utilization after repair, although it remains unclear
      whether individual components of the ASG score independently contribute to
      survival. This study analyzed and validated an aortic and iliac artery calcium
      scoring system that can potentially predict survival after AAA repair. METHODS:
      Patients who underwent infrarenal AAA repairs from July 2007 to May 2012 were
      analyzed using complete 5-year records. Those who died <=30 days of surgery were
      excluded. Calcium score (CS) was defined using the ASG scoring system for its
      basis by preoperative imaging <6 months before surgery. A CS for any patient was
      0 to 5 points, the sum of the points assigned to aortic neck (2 points total) and
      iliac artery (3 points total) calcification. A receiver operating characteristic
      curve was used to determine a CS threshold for mortality. The 5-year survivors
      and deaths were compared in regard to comorbidities, pharmacology, and CS at or
      above the defined threshold. Each variable with a P value <.1 between the groups
      was then placed into a Cox proportional hazards model, with statistical
      significance of P < .05. RESULTS: There were 356 patients who underwent AAA
      repair with complete 5-year follow-up data; 26% died within 5 years of surgery.
      Of these, 13% had CS of 0 with 15% mortality, 28% had CS of 1 with 21% mortality,
      24% had CS of 2 with 24% mortality, 23% had CS of 3 with 35% mortality, 10% had
      CS of 4 with 40% mortality, and 2% had CS of 5 with 17% mortality. The receiver
      operating characteristic curve demonstrated an appropriate threshold of CS 3. Of
      these patients, 65% had a CS <3, whereas 35% had a CS >=3. Patients with a CS >=3
      had a lower 5-year survival probability (P = .003). Comparing 5-year survivors
      and deaths in a Cox proportional hazards analysis, CS >=3 was associated with a
      hazard ratio of 1.579 (95% confidence interval, 1.038-2.402; P = .0328).
      CONCLUSIONS: A CS >=3 is linked to a lower 5-year survival after AAA repair in
      our population. This system potentially can be another measure for risk
      stratification and serve as a means to predict midterm mortality in AAA repairs.
      Future study will be needed for further validation to predict midterm mortality
      and to better guide surgical decision-making.

PMID- 30292613
TI  - Randomized multicenter trial on percutaneous versus open access in endovascular
      aneurysm repair (PiERO).
AB  - BACKGROUND: In endovascular valve and aortic repair, vascular access through a
      percutaneous approach has become the competing technique to an open surgical
      approach. The effect on postoperative complications and surgical site infections
      (SSIs) has been investigated, but randomized evidence is lacking. The objective
      was to investigate whether percutaneous access of the common femoral artery (CFA)
      with a percutaneous closure device would decrease the number of SSIs compared
      with open surgical access of the CFA in endovascular aneurysm repair (EVAR).
      METHODS: Patients with an abdominal aortic aneurysm suitable for EVAR were
      randomized to open or percutaneous access of the main device (MD) through the
      CFA. Through the contralateral side, access was obtained with the other technique
      than the one for which the MD was randomized. The primary outcome was number of
      SSIs. Secondary outcomes were wound complications, visual analog scale for pain
      scores, and standardized wound assessment scores during follow-up. Preoperative
      screening culture and groin biopsy specimens were obtained from all patients.
      RESULTS: Both groups contained 137 groins. SSI rate was 1.5% in the open group vs
      0% in the percutaneous group. For MDs only, SSI rate was 3.1% (odds ratio, 3.3;
      95% confidence interval, 0.31-347; P = .34). Wound complications were comparable
      in both groups. Neither nasal nor groin Staphylococcus aureus carriage had a
      significant effect on SSIs, Southampton Wound Assessment score, or visual analog
      scale score. Adjusted pain score was 0.69 lower, in favor of percutaneous access.
      Wound assessment was better after 2 weeks (odds ratio, 3.57; 95% confidence
      interval, 1.02-12.44; P = .046), also in favor of percutaneous access.
      CONCLUSIONS: Percutaneous access of the CFA does not reduce the number of SSIs.
      It does, however, reduce pain and improve wound healing with less inflammation 1
      day and 2 weeks after EVAR, respectively.

PMID- 30292614
TI  - Patients with large neck diameter have a higher risk of type IA endoleaks and
      aneurysm rupture after standard endovascular aneurysm repair.
AB  - OBJECTIVE: Standard endovascular aneurysm repair (EVAR) is the most common
      treatment of abdominal aortic aneurysms (AAAs). EVAR has been increasingly used
      in patients with hostile neck features. This study investigated the outcomes of
      EVAR in patients with neck diameters >=30 mm in the prospectively maintained
      Endurant Stent Graft Natural Selection Global Postmarket Registry (ENGAGE).
      METHODS: This is a retrospective study comparing patients with neck diameters
      >=30 mm with patients with neck diameters <30 mm. The primary end point was type
      IA endoleak (EL1A). Secondary end points included secondary interventions to
      correct EL1A, aneurysm rupture, and survival. RESULTS: This study included 1257
      patients (mean age, 73.1 years; 89.4% male) observed for a median 4.0 years
      (interquartile range, 2.7-4.8 years). A total of 97 (7.7%) patients had
      infrarenal neck diameters >=30 mm and were compared with the remaining 1160
      (92.3%) with neck diameters <30 mm. At baseline, there were no differences
      between groups regarding demographics and comorbidities other than cardiac
      disease, which was more frequent in the >=30-mm neck diameter group (P = .037).
      There were no significant differences between the groups regarding neck length,
      angulation, thrombus, or calcification. Mean preoperative AAA diameter was 64.6
      +/- 11.3 mm in the >=30-mm neck diameter group and 60.0 +/- 11.6 mm in the <30-mm
      neck diameter group (P < .001). Stent graft oversizing was significantly less in
      the >=30-mm neck diameter group (12.2% +/- 8.9% vs 22.1% +/- 11.9%; P <. 001).
      Five patients (5.2%) in the >=30-mm neck diameter group and 30 (2.6%) with neck
      diameters <30 mm developed EL1A, yielding a 4-year freedom from EL1A of 92.4% vs
      96.6%, respectively (P = .09). Oversizing was 21.8% +/- 13.0% for patients
      developing EL1A and 21.3% +/- 12.4% for the remaining cohort (P = .99). In
      adjusting for neck length, AAA diameter, and device oversizing, patients with
      neck diameter >=30 mm were at greater risk for development of EL1A (hazard ratio,
      3.0; 95% confidence interval, 1.0-9.3; P = .05). Secondary interventions due to
      EL1A did not differ between groups (P = .36). AAA rupture occurred in three
      patients with neck diameter >=30 mm (3.1%) and in eight patients with neck
      diameter <30 mm (0.7%; hazard ratio, 5.1; 95% confidence interval, 1.4-19.2; P =
      .016); two cases were EL1A related in each group. At 4 years, overall survival
      was 61.6% for the >=30-mm neck diameter group and 75.2% for the <30-mm neck
      diameter group (P = .009), which remained significant on correcting for sex and
      AAA diameter (P = .016). CONCLUSIONS: In this study, patients with infrarenal
      neck diameter >=30 mm had a threefold increased risk of EL1A and fivefold risk of
      aneurysm rupture after EVAR as well as worse overall survival. This may influence
      the choice of AAA repair and underlines the need for regular computed tomography
      based imaging surveillance in this subset of patients. Furthermore, these results
      can serve as standards with which new, possibly improved technology, such as
      EndoAnchors (Medtronic, Santa Rosa, Calif), can be compared.

PMID- 30292615
TI  - The distance of the primary intimal tear from the left subclavian artery predicts
      aortic growth in uncomplicated type B aortic dissection.
AB  - OBJECTIVE: Controversy exists about the optimal treatment of acute uncomplicated
      type B aortic dissection (auTBAD). Optimal medical therapy (OMT) provides
      excellent short-term outcomes, but long-term results are poor. Ideally, auTBAD
      patients who will fail to respond to OMT in the chronic phase could be identified
      and undergo thoracic endovascular aortic repair. The purpose of this study was to
      identify radiographic predictors of auTBAD patients who will fail to respond to
      OMT. METHODS: A review of the Emory aortic database from 2000 to 2017 identified
      320 auTBAD patients initially treated with OMT. From this cohort, 121 patients
      with two or more contrast-enhanced imaging scans were available for analysis.
      These patients were initially divided into groups based on growth of the thoracic
      aorta >=10 mm or intervention due to aneurysmal growth: growth (n = 72) and no
      growth (n = 49). TeraRecon (Foster City, Calif) imaging software was used to
      analyze characteristics of the primary intimal tear (PIT), false lumen, and
      overall aortic size. Finally, Cox proportional hazards models were constructed to
      estimate hazard ratios and to identify predictors of OMT failure. RESULTS: The
      mean age of all patients was 54 +/- 11 years, and 67% were male. Thirty-eight
      patients (53%) in the growth group underwent intervention. There were no
      differences between groups in age, hypertension, diabetes mellitus, tobacco
      abuse, or chronic obstructive pulmonary disease. The distance of the PIT from the
      left subclavian artery in patients with auTBAD was significantly shorter in the
      growth group (growth, 27 mm [9-66 mm]; no growth, 77 mm [26-142 mm]; P < .01).
      Multivariable Cox regression analysis identified the distance of the PIT from the
      left subclavian artery and a thoracic aortic diameter >45 mm as independent
      predictors of failure of OMT. Partial false lumen thrombosis was not a predictor
      of aortic growth. CONCLUSIONS: The distance of the PIT from the left subclavian
      artery is a predictor of aortic growth in auTBAD. Patients with a primary tear
      located in zone 3 of the proximal descending thoracic aorta should be monitored
      closely and may be considered for early thoracic endovascular aortic repair in
      the setting of auTBAD.

PMID- 30292616
TI  - Contrast-induced nephropathy after peripheral vascular intervention: Long-term
      renal outcome and risk factors for progressive renal dysfunction.
AB  - OBJECTIVE: Contrast-induced nephropathy (CIN) is a frequently used quality
      outcome marker after peripheral vascular interventions (PVIs). Whereas the
      factors associated with CIN development have been well documented, the long-term
      renal effects of CIN after PVI are unknown. This study was undertaken to
      investigate the long-term (1-year) renal consequences of CIN after PVI and to
      identify factors associated with renal function deterioration at 1-year follow
      up. METHODS: From 2008 to 2015, patients who had PVI at our institution (who were
      part of a statewide Vascular Interventions Collaborative) were queried for those
      who developed CIN. CIN was defined by the Collaborative as an increase in serum
      creatinine concentration of at least 0.5 mg/dL within 30 days after intervention.
      Preprocedural dialysis patients or patients without postprocedural creatinine
      values were excluded. Preprocedural, postprocedural, and 1-year serum creatinine
      values were abstracted and used to estimate glomerular filtration rate (GFR).
      DeltaGFR was defined as preprocedural GFR minus 1-year GFR. Univariate and
      multivariate analyses for DeltaGFR were performed to determine factors associated
      with renal deterioration at 1 year. RESULTS: From 2008 to 2015, there were 1323
      PVIs performed; 881 patients met the inclusion criteria. Of these, 57 (6.5%)
      developed CIN; 47% were male, and 51% had baseline chronic kidney disease. CIN
      resolved by discharge in 30 patients (53%). Using multivariate linear regression,
      male sex (P = .027) and congestive heart failure (P = .048) were associated with
      1-year GFR decline. Periprocedural variables related to 1-year GFR decline
      included percentage increase in 30-day postprocedural creatinine concentration (P
      = .025), whereas CIN resolution by discharge (mean, 13.1 days) was protective for
      renal function at 1 year (P = .02). A post hoc analysis was performed with 50 PVI
      patients (randomly selected) who did not develop CIN, comparing their late renal
      function with that of the CIN group stratified by the periprocedural 30-day
      variables. Patients with CIN resolution at discharge had similar 1-year renal
      outcomes to non-CIN patients, whereas the CIN-persistent (at discharge) patients
      had greater renal deterioration at 1 year compared with non-CIN patients (P =
      .016). CONCLUSIONS: Male sex and congestive heart failure are risk factors for
      further renal function decline in patients developing CIN after PVI. The
      magnitude and duration of increase in creatinine concentration (CIN persistence
      at discharge) correlated with late progressive renal dysfunction in CIN patients,
      suggesting that early-resolving CIN is relatively benign.

PMID- 30292617
TI  - Lateral femoral bypass for prosthetic arterial graft infections in the groin.
AB  - OBJECTIVE: Prosthetic arterial graft infections (PAGIs) in the groin pose
      significant challenges in terms of revascularization options and risk of limb
      loss as well as associated morbidities. Although obturator canal bypass (OCB) has
      been suggested for revascularization of the extremity in these cases, moderate
      success rates and technical challenges have limited widespread use. Our study
      analyzed lateral femoral bypass (LFB) as an alternative approach for the
      treatment of groin PAGIs. METHODS: This is a retrospective review of a
      prospectively maintained database of patients who underwent LFB for groin PAGIs
      at a single center from 2000 to 2017. Patients' data including demographics,
      comorbidities, perioperative complications, graft patency, and need for
      reintervention were used. Patients were observed after LFB with duplex ultrasound
      surveillance in an accredited noninvasive vascular laboratory every 3 months
      during the first year, followed by every 6 months for the second year and yearly
      thereafter. After isolation of the infected wound with sterile dressings, remote
      proximal and distal arterial exposure incisions were made. LFBs were tunneled
      under the inguinal ligament and lateral to the infected wound from an uninvolved
      inflow artery or bypass graft to an uninvolved outflow vessel. RESULTS: A total
      of 19 LFBs were performed in 16 patients (mean age, 69 +/- 12.6 years). Three
      LFBs were performed urgently for acute bleeding. Choice of conduit included 6
      (31.6%) autogenous vein grafts, 10 (52.6%) cadaveric grafts, 2 (10.5%) rifampin
      soaked Dacron grafts, and 1 (5.3%) polytetrafluoroethylene graft. Average follow
      up was 33 months (range, 0-103 months). Major adverse events occurring within 30
      days of the operation included one (5.3%) death and one (5.3%) graft excision for
      pseudoaneurysm. Primary patency and primary assisted patency at 12 and 24 months
      were 73% and 83%, respectively. One patient required an amputation 17 months
      after surgery after failure of repeated revascularization attempts. Overall limb
      salvage was 93.8% during this follow-up period. CONCLUSIONS: In this series, LFB
      for management of groin PAGIs demonstrated higher patency and limb salvage rates
      compared with previous reports of OCB. Diligent postoperative duplex ultrasound
      surveillance is critical to the achievement of limb salvage and maintenance of
      graft patency. These results suggest that LFB, which is technically less complex
      than OCB, should be considered the first choice for revascularization in select
      cases of PAGIs involving the groin.

PMID- 30292618
TI  - Serum resistin is associated with impaired endothelial function and a higher rate
      of adverse cardiac events in patients with peripheral artery disease.
AB  - OBJECTIVE: Resistin is a hormone that has been associated with metabolic syndrome
      and cardiovascular disease. The role of resistin in patients with peripheral
      artery disease (PAD) has not been fully explored. This study seeks to understand
      the relationship between serum resistin, vascular function, and cardiovascular
      outcomes in patients with PAD. METHODS: There were 106 patients with PAD who were
      recruited between 2011 and 2016. Patients attended a baseline visit during which
      a comprehensive vascular physiology assessment including medical and surgical
      history, radial artery tonometry, and flow mediated-vasodilation (FMD) was
      completed. A blood sample was drawn, and serum resistin was assayed using enzyme
      linked immunosorbent assay kits. Using the time of study enrollment as the time
      of origin, incident major adverse cardiac events (MACEs) were identified by
      subsequent chart review and defined as a composite end point of myocardial
      infarction, coronary revascularization, transient ischemic attack, stroke, or
      death from a cardiac cause. RESULTS: Patients had a mean age of 68 +/- 8 years,
      were largely white (75%), and had comorbidities commonly associated with PAD
      including hypertension (92%), hyperlipidemia (87%), coronary artery disease
      (37%), and diabetes mellitus (38%). After stratification by resistin quartile,
      higher resistin quartiles were significantly associated with an older age, a
      greater number of pack-years smoked, and a lower estimated glomerular filtration
      rate. Despite similar comorbidities and medication use, endothelial function, as
      measured by FMD, was significantly lower with increasing resistin quartile (I,
      9.1% +/- 3.3%; II, 7.1% +/- 3.5%; III, 5.8% +/- 4.0%; IV, 5.6% +/- 3.5%; P =
      .002). In multivariable linear regression, higher resistin quartiles (III and IV)
      were associated with lower FMD relative to quartile I after adjusting for several
      patient characteristics, medications, and comorbidities (III, -2.26 [95%
      confidence interval (CI), -4.51 to -0.01; P = .05]; IV, -2.53 [95% CI, -4.87 to 
      0.20; P = .03]). During a median follow-up period of 36 months (interquartile
      range, 29-45 months), 21 patients experienced the primary end point. In a Cox
      proportional hazards model adjusted for smoking status, coronary artery disease,
      and age, each 1 ng/mL increase in resistin was associated with a 10% increased
      risk of MACEs (hazard ratio, 1.10; 95% CI, 1.00-1.20; P = .04). CONCLUSIONS: In
      patients with PAD, higher levels of resistin were associated with impaired
      endothelial function and an increased rate of MACEs. These results suggest that
      resistin may be a marker or effector of impaired vascular physiology and adverse
      cardiac outcomes in patients with PAD. Further research is needed to determine
      the potential mechanisms by which resistin may impair endothelial function and
      increase MACEs in this population.

PMID- 30292619
TI  - Gender-related outcomes after open repair of descending thoracic and
      thoracoabdominal aortic aneurysms.
AB  - OBJECTIVE: Female sex has been associated with greater morbidity and mortality
      for a variety of major cardiovascular procedures. We sought to determine the
      influence of female sex on early and late outcomes after open descending thoracic
      aortic aneurysm (DTA) and thoracoabdominal aortic aneurysm (TAAA) repair.
      METHODS: We searched our aortic surgery database to identify patients having open
      DTA or TAAA repair. Logistic regression and Cox regression analyses were used to
      assess the effect of sex on perioperative and long-term outcomes. RESULTS: From
      1997 until 2017, there were 783 patients who underwent DTA or TAAA repair. There
      were 462 male patients and 321 female patients. Female patients were
      significantly older (67.6 +/- 13.9 years vs 62.6 +/- 14.7 years; P < .001), had
      more chronic pulmonary disease (47.0% vs 35.7%; P = .001) and forced expiratory
      volume in 1 second <50% (28.3% vs 18.2%; P < .001), and were more likely to have
      degenerative aneurysms (61.7% vs 41.6%; P < .001). Operative mortality was not
      different between women and men (5.6% vs 6.2%; P = .536). However, women were
      more likely to require a tracheostomy after surgery (10.6% vs 5.0%; P = .003)
      despite a reduced incidence of left recurrent nerve palsy (3.4% vs 7.8%; P =
      .012). Logistic regression found female sex to be an independent risk factor for
      a composite of major adverse events (odds ratio, 2.68; confidence interval, 1.41
      5.11) and need for tracheostomy (odds ratio, 3.73; confidence interval, 1.53
      9.10). Women also had significantly lower 5-year survival. CONCLUSIONS: Women
      undergoing open DTA or TAAA repair are not at greater risk for operative
      mortality than their male counterparts are. Reduced preoperative pulmonary
      function may contribute to an increased risk for respiratory failure in the
      perioperative period.

PMID- 30292620
TI  - Toxicogenomic responses to zearalenone in Caenorhabditis elegans reveal possible
      molecular mechanisms of reproductive toxicity.
AB  - In this study, the possible molecular mechanisms of zearalenone (ZEA)-induced
      reproductive and developmental toxic effects in Caenorhabditis elegans (C.
      elegans) were investigated. Differential gene expression profiles were
      identified, and 171, 245, and 3149 genes were down- or up-regulated (>2.0 fold)
      in 10, 20, and 40 MUg/ml ZEA treated groups, respectively, as compared to
      untreated controls. Pathway specific mapping showed that the major differentially
      expressed genes were collagen synthetic pathways regulating genes, col-121 and
      dpy-17. Real-time PCR reconfirmation of key genes, related to cuticle collagen
      synthetic pathway, found dramatic changes in the expression of the genes dpy-31,
      sqt-3, col-121, and dpy-17 following exposure to ZEA (40 MUg/ml), which indicated
      the significance of these genes in ZEA-induced toxicity. Cuticle collagen plays
      many key roles in the development and reproduction of C. elegans. The
      hypersensitive responses in transgenic and mutant worms also confirmed the roles
      of these genes in lethality and reproductive response to ZEA exposure, which
      indicates that ZEA blocked the normal collagen processing and cuticle formation.
      Taken together, our results demonstrate that disruption of the collagen
      biosynthetic pathway might be a key mechanism in ZEA-induced reproductive and
      developmental toxic effects in C. elegans.

PMID- 30292621
TI  - RIFM fragrance ingredient safety assessment, methyl phenylacetate, CAS Registry
      Number 101-41-7.

PMID- 30292622
TI  - Hypocholesterolaemic and antioxidant properties of Olea europaea L. leaves from
      Chlef province, Algeria using in vitro, in vivo and in silico approaches.
AB  - Aqueous and ethanol extracts prepared from leaves of Olea europaea L. were
      evaluated for in vitro antioxidant and in vivo hypocholesterolemic effect. The
      result of administration of O. europaea leaf extracts on serum total cholesterol,
      triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and
      very low-density lipoprotein (VLDL) in hypercholesterolaemic mice was evaluated.
      In addition, rutin and luteolin, reported to occur naturally in O. europaea
      leaves, were docked against HMG-CoA reductase, the rate-limiting enzyme in
      cholesterol metabolism. Mice treated with both extracts showed reduced total
      cholesterol (246.6 and 163.4 mg/dl, for mice groups treated with respective
      extracts) and LDL (150.16 and 81.28 mg/dl, for mice groups treated with
      respective extracts) levels as compared to the hypercholesterolaemic group (total
      cholesterol 253.00 mg/dl and LDL 160.00 mg/dl). Mice treated with aqueous extract
      (200 mg/kg body weight) showed significantly reduced triglyceride and VLDL levels
      as compared to the group treated with atorvastatine. HDL level of mice
      administered with O. europaea aqueous extract was comparable to the atorvastatine
      treated group. The ethanol extract of O. europeae leaves was a potent antioxidant
      (IC50 69.15 mg/ml, % inhibition 54.98, 82.63 mg ascorbic acid equivalent/g
      extract, 7.53 mol of Fe2+/g extract, and % inhibition 49.71, for the DPPH, beta
      carotene bleaching, total antioxidant capacity, FRAP, and ferric thiocyanate
      assays, respectively). Docking studies revealed that rutin showed higher binding
      affinity with HMG-CoA reductase as compared to luteolin. Data gathered from this
      study support the development of a prophylactic biomedicine from O. europaea
      leaves for the management of hypercholesterolemia and atherosclerosis.

PMID- 30292623
TI  - RIFM fragrance ingredient safety assessment, endo-1,2,3,3
      tetramethylbicyclo[2.2.1]heptan-2-ol, CAS Registry Number 28462-85-3.

PMID- 30292624
TI  - Radical Mastectomy Increases Psychological Distress in Young Breast Cancer
      Patients: Results of A Cross-sectional Study.
AB  - INTRODUCTION: The present study aimed to detect the factors associated with
      psychological distress (PD) in young Moroccan patients with breast cancer, with a
      special focus on the type of surgical procedure. PATIENTS AND METHODS: We
      collected social, demographic, and clinical data from female patients, aged < 45
      years, with localized stage breast cancer who had undergone either radical
      mastectomy or conservative surgery and for whom adjuvant chemotherapy was
      indicated. We used the Hospital Anxiety and Depression Scale (HADS) to assess the
      psychological status. The relationship between the variables and PD was analyzed
      using simple and multiple logistic regression analyses. RESULTS: A total of 122
      women were enrolled, of whom 41 (33.6%) had a HADS global score >= 15. The HAD
      anxiety and depression subscores were >= 11 for 10 (8.2%) and 8 (6.6%) patients,
      respectively. On multivariate analysis, adjusted for marital status and receipt
      of analgesic and/or anxiolytic treatment, we found that radical mastectomy (odds
      ratio [OR], 5.747; 95% confidence interval [CI], 1.342-24.608), living in a
      difficult emotional (OR, 7.366; 95% CI, 1.727-31.41) and/or financial (OR,
      16.521; 95% CI, 3.574-76.36) situation, and a lack of social and/or family
      support (OR, 19.617; 95% CI, 3.549-108.43) were independent factors associated
      with PD. CONCLUSION: Breast-conserving surgery should be performed whenever
      possible for young women to avoid the psychological repercussions of radical
      procedures.

PMID- 30292625
TI  - Real-World Experience of Palbociclib-Induced Adverse Events and Compliance With
      Complete Blood Count Monitoring in Women With Hormone Receptor-Positive/HER2
      Negative Metastatic Breast Cancer.
AB  - BACKGROUND: The cyclin-dependent kinase 4/6 inhibitor palbociclib has emerged as
      a novel therapeutic agent in metastatic breast cancer. Neutropenia is commonly
      observed, and thus stringent treatment guidelines regarding complete blood count
      (CBC) monitoring have been developed. The aim of this study was to provide a real
      world experience of the toxicities associated with palbociclib therapy and to
      evaluate compliance with CBC monitoring. PATIENTS AND METHODS: We performed a
      retrospective single-center audit of hormone receptor-positive metastatic breast
      cancer patients treated with palbociclib over a 6-month period in an Irish
      tertiary referral hospital. RESULTS: A total of 64 patients were included in the
      analysis. Palbociclib was most commonly used in combination with letrozole (n =
      40). A total of 28 patients (44%; 95% confidence interval, 31.2-56.2) had
      treatment deferrals due to neutropenia, with a median time to first deferral of 4
      weeks. Fifteen patients (23%; 95% confidence interval, 15.4-37.7) required dose
      adjustments; however, there was no association with an increased risk of
      progressive disease (P = .56). Only 3 patients discontinued treatment as a result
      of poor tolerance. Adverse events were as expected; however, 7 venous
      thromboembolic events were reported. CONCLUSION: Compliance was good with
      existing CBC monitoring guidelines. We observed an 11% incidence of venous
      thromboembolic events, a significant increase from 2% reported in the PALOMA-3
      trial. Further studies are recommended to determine if prophylactic
      anticoagulation may benefit these patients.

PMID- 30292626
TI  - Hydropic leiomyoma: a distinct variant of leiomyoma closely related to HMGA2
      overexpression.
AB  - Hydropic leiomyoma (HLM) is a variant of uterine leiomyoma with characteristic
      features of zonal distributions of edema, increased vascularity, and tumor cells
      arranged in nodules or cords. Diagnostic difficulty and patient management are
      further complicated by a lack of studies and unknown cause of the disease. To
      study this tumor's nature, 24 HLM cases were selected for analysis of cyto
      histologic features, immunohistochemical profile (HMGA2, FH, CD34, pAKT, p16, ER,
      SMA and Ki-67), and molecular alterations of HMGA2 by fluorescence in-situ
      hybridization (FISH) and MED12 mutations. HLM showed large tumor size (average
      14.4cm) and unique histology, characterized by edematous areas of tumor cells
      with mostly round-oval nuclei, arranged in cords and/or with perinodular growth
      around vessels, and increased thick-walled vessels (average 17 vessels/10x medium
      power field). Immunohistochemistry revealed that 76% (18/24) of HLM had HMGA2
      overexpression, 32% (6/19) of which harbored HMGA2 rearrangement detected by
      FISH. Thick-walled vessels in HLM were composed of mostly HMGA2 positive tumor
      cells; and HLM with HMGA2 overexpression also showed CD34 positive tumor vessel
      supporting pericytes. In contrast to usual type leiomyoma with a high frequency
      of MED12 mutations, no MED12 mutations were found in any HLM. HLM showed
      increased pAKT activity, indicating a strong contribution of AKT pathway
      signaling in HLM promoting tumor growth. Our findings suggest that HLM is a
      distinct variant of uterine smooth muscle tumor likely driven by HMGA2
      overexpression.

PMID- 30292627
TI  - Is immunohistochemical staining for beta-catenin the definitive pathological
      diagnostic tool for desmoid-type fibromatosis?: a multi-institutional study.
AB  - Immunohistochemical staining with anti-beta-catenin antibody has been applied as
      a diagnostic tool for desmoid-type fibromatoses (DF). In recent years, specific
      gene mutation (CTNNB1) analysis has also been reported to be useful for diagnosis
      of DF, however the association between CTNNB1 mutation status and
      immunohistochemical staining pattern of beta-catenin is rarely reported. The
      purpose of this study is to clarify the relationship of the staining pattern of
      beta-catenin with the CTNNB1 mutation status and various clinical variables, and
      investigate the significance of immunohistochemical staining of beta-catenin in
      cases diagnosed with DF. Between 1997 and 2017, 104 cases diagnosed with DF from
      6 institutions in Japan were enrolled in this study: Nagoya University; National
      Cancer Center Hospital; Niigata University; Okayama University; Kyushu
      University, and Cancer Institute Hospital. For all cases, immunohistochemical
      staining of beta-catenin and gene mutation analysis of CTNNB1 were performed. Of
      104 cases, 87 (84%) showed nuclear staining of beta-catenin, and 95 (91%)
      positive staining in cytoplasm. The proportion of cases showing strong nuclear
      staining of beta-catenin was significantly higher in the cases with S45F than in
      those with T41A or wild type (WT). The proportion of cases stained strongly in
      the cytoplasm rather than in the nucleus was significantly higher in the group of
      T41A than that of S45F or WT. Among 17 cases in which nuclear immunostaining were
      absent, CTNNB1 mutation was observed in 5 cases (29.4%). There were unignorable
      cases of DF with negative beta-catenin immunostaining despite a definitive
      clinical and pathological diagnosis of DF and/or positive CTNNB1 mutation.

PMID- 30292628
TI  - Development of a Prediction Tool for Exclusive Locoregional Recurrence After
      Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer.
AB  - BACKGROUND: Limited information is available about the pattern of relapse after
      perioperative chemotherapy with radical cystectomy (RC) vs. RC alone in muscle
      invasive bladder cancer. PATIENTS AND METHODS: Data from 1082 patients of the
      Retrospective International Study of Invasive/Advanced Cancer of the Urothelium
      database, treated from February 1990 to December 2013 at 27 centers in the United
      States, Europe, Israel, and Canada, were collected. Locoregional relapse was
      defined as any pelvic lymph node or soft tissue-only recurrences. Cumulative
      incidence methods were used to estimate time to locoregional relapse (TTRL). Cox
      regression analyses were performed and a nomogram for 12-month locoregional
      relapse-free survival (RFS) was developed. The nomogram was applied to an
      external data set (n = 1021). RESULTS: A total of 517 patients (47.8%) developed
      a relapse: 177 (16.4%) exclusive locoregional relapse. In multivariable analyses,
      perioperative chemotherapy was associated with longer TTRL (P < .001). Other
      factors were nonurothelial histology (P = .013), pT-stage (P < .001), and
      surgical margins (P < .001). The concordance index of the model was 0.681 (95%
      bootstrapped confidence interval, 0.666-0.716). Risk group categories were
      obtained according to nomogram tertiles. Despite, overall, observed locoregional
      RFS in the validation cohort exceeding predicted results, for high-risk patients
      (80 points or less, lowest nomogram tertile) observed 12-month RFS was similar
      between development and validation cohorts (60.1% and 66.6%). The study is
      limited by its retrospective nature. CONCLUSION: In the largest study, to our
      knowledge, that analyzed locoregional recurrences after RC, we propose a risk
      prediction tool for exclusive locoregional failures that might be suitable for
      clinical studies. Patients best suited for adjuvant radiotherapy might be those
      within the lowest nomogram tertile. Prospective trials are needed to validate
      findings.

PMID- 30292629
TI  - Establishment of a protein biochip to detect serum IgG antibodies against IL-2
      and soluble CD25 in hemophagocytic lymphohistiocytosis.
AB  - BACKGROUND: Interleukin-2 (IL-2) and soluble CD25 (sCD25) are among the most
      important cytokines and diagnostic biomarkers in hemophagocytic
      lymphohistiocytosis (HLH). Detecting serum level of IL-2 and sCD25 is valuable
      for making clinical diagnosis and treatment decision in HLH. METHODS: Since tests
      showing serum IgG antibody against IL-2 or sCD25 have never been carried out, a
      new protein biochip, which was modified with cysteine and activated sophorolipid
      (Cys-SL), was developed. RESULTS: Limits of detection on the biochip were 78
      pg/ml for IL-2 and 39 pg/ml for sCD25, respectively. The data showed that on-chip
      seroimmunological responses to IL-2 and sCD25 proteins were 20.8% and 83.1% and
      the seroprevalence of IL-2 and sCD25 IgG antibodies were 45.5% and 57.2%,
      respectively. Data collection for the seroprevalence of serum antigen-antibody
      complex of sCD25 was 68.8%. The new biochip model shared similar sensitivity and
      specificity to chemiluminescent immunoassay (CLIA) in its measuring capacity of
      serum sCD25. CONCLUSIONS: We addressed and confirmed the involvement of serum IgG
      antibodies against IL-2 and sCD25 as well as Ag-Ab complex of sCD25 in HLH
      patients. Therefore, this biochip platform would offer a new technological
      substitution for clinical serological diagnosis of HLH.

PMID- 30292630
TI  - Targeted exome sequencing identified a novel mutation hotspot and a deletion in
      Chinese primary hypertrophic osteoarthropathy patients.
AB  - BACKGROUND: Primary hypertrophic osteoarthropathy (PHO) is a genetically and
      clinically heterogeneous systematic disorder caused by mutations in genes HPGD
      and SLCO2A1. The purpose of the present study is to provide useful information
      for the early and precise diagnosis of PHO and identify causative mutations in
      Chinese PHO children. METHODS AND RESULTS: The clinical manifestations,
      radiographic features of seven Chinese pediatric patients were systematically
      analyzed. Targeted exome sequencing identified a previously reported
      c.310_311delCT mutation and a novel common splicing site mutation c.324 + 5G > A
      in the HPGD gene. Relative quantitative real time PCR validated a novel deletion
      of the exon 4 in the same gene. Neither mutations nor structural variations in
      the gene SLCO2A1 were detected. CONCLUSIONS: In the present study, homozygous or
      compound heterozygous HPGD mutations were identified in seven Chinese pediatric
      patients, suggesting an autosomal recessive inheritance. The c.310_311delCT
      mutation and the splicing site mutation c.324 + 5G > A were likely to be
      mutational hotspots in Chinese PHO patients. For the first time, a structural
      variation of the HPGD gene was reported. Homozygous, compound heterozygous
      mutations or structural variation identified in the HPGD gene proposed that
      targeted exome sequencing may be a preferable method for pediatric PHO diagnosis
      and mutation analysis.

PMID- 30292631
TI  - Quality specifications and their daily application to evaluate the accuracy of
      reference measurements for serum concentrations of 25-hydroxyvitamin D3 and 25
      hydroxyvitamin D2.
AB  - BACKGROUND: Reference measurement procedures (RMP) have rigorous accuracy
      specifications. For total 25-hydroxyvitamin D, 25(OH)D, bias <=1.7% and CV <=5%
      are recommended. These quality specifications are impractical for minor analytes,
      such as 25(OH)D2. Furthermore, documentation on RMP quality performance
      specifications for the individual 25(OH)D metabolites and their daily application
      are missing. METHODS: To assess accuracy, we used zeta-scores. Daily, 5-10
      specimens (duplicate) and 3 reference materials (singleton or duplicate) were
      measured for 25(OH)D3 and 25(OH)D2 using JCTLM-accepted LC-MS/MS RMPs. Protocols
      were repeated on 3-4 occasions to generate campaign results. We used separate
      zeta-score acceptability criteria for daily (<=|2|) and campaign (<=|1|)
      evaluations. Allowable imprecision was determined experimentally. RESULTS: Across
      7 campaigns, unacceptable daily zeta-scores required repeating 2 runs for
      25(OH)D3 and 5 runs for 25(OH)D2. Hence, the zeta-scores of acceptable reference
      material results indicated high accuracy. The allowable imprecision for the RMPs
      was <=5% (daily) and <= 3% (campaign) for 25(OH)D3 and <= 7% (daily) and <= 4%
      (campaign) for 25(OH)D2, respectively. CONCLUSIONS: Using zeta-scores and
      experimentally derived imprecision, we developed a straightforward approach to
      assess the acceptability of individual 25(OH)D reference measurements, providing
      also much-needed practical accuracy specifications for 25(OH)D2.

PMID- 30292632
TI  - Is capillary zone electrophoresis a suitable method for estimating serum albumin:
      A comparison of four methods.
AB  - BACKGROUND: The capillary zone electrophoresis method of albumin measurement is
      frequently used for oncologic and haematologic patients but few data exist about
      the agreement between the albumin measurements performed by capillary zone
      electrophoresis and other methods. The aim of this study was to analyse the
      agreement between human serum albumin measurements by capillary zone
      electrophoresis and by the nephelometry, bromocresol purple and turbidimetry
      methods. METHOD: We prospectively measured 100 freshly collected non-frozen
      patient serum samples, by using four different methods: the capillary zone
      electrophoresis method performed with a CAPILLARYS 2 instrument, the bromocresol
      purple dye method performed with an Advia XPT analyser, the nephelometric method
      performed with a BN ProSpec analyser and the turbidimetric method with reagents
      from DiAgam and performed with the Advia XPT analyser. RESULTS: A bias towards
      higher values in the lower range of albumin concentrations was observed with
      capillary zone electrophoresis compared to immunonephelometry: correlation
      coefficient r2 = 0.925; slope of 0.86 (0.82-0.89, 95% confidence interval), which
      is significantly different from 1; and an intercept of 4.94 g/L (3.67-6.16, 95%
      confidence interval). Similar results were observed when comparing capillary zone
      electrophoresis to the bromocresol purple and immunoturbidimetry methods. The
      capillary electrophoresis method overestimated low albumin levels by up to 25% (5
      g/L). CONCLUSION: Compared to the nephelometry, turbidimetry and bromocresol
      purple methods, the capillary zone electrophoresis method tends to overestimate
      human serum albumin concentrations for levels below 30 g/L. This discrepancy
      could lead to an overestimation of the nutritional status, an inappropriate
      scoring of the disease and a delay in nutritional treatment.

PMID- 30292633
TI  - Endoplasmic reticulum stress induces inverse regulations of major functions in
      portal myofibroblasts during liver fibrosis progression.
AB  - Portal myofibroblasts (PMF) form a sub-population of highly proliferative and
      proangiogenic liver myofibroblasts that derive from portal mesenchymal
      progenitors. Endoplasmic reticulum (ER) stress was previously shown to modulate
      fibrogenesis, notably in the liver. Our aim was to determine if ER stress
      occurred in PMF and affected their functions. PMF were obtained after their
      expansion in vivo from bile duct-ligated (BDL) rats and referred to as BDL PMF.
      Compared to standard PMF obtained from normal rats, BDL PMF were more
      myofibroblastic, as assessed by higher alpha-smooth muscle actin expression and
      collagen 1 production. Their proangiogenic properties were also higher, whereas
      their proliferative and migratory capacities were lower. CHOP expression was
      detected in the liver of BDL rats, at the leading edge of portal fibrosis where
      PMF accumulate. BDL PMF displayed ER dilatation and an overexpression of the PERK
      pathway downstream targets, Chop, Gadd34 and Trb3, in comparison with standard
      PMF. In vitro, the induction of ER stress by tunicamycin in standard PMF, caused
      a decrease in their proliferative and migratory activity, and an increase in
      their proangiogenic activity, without affecting their myofibroblastic
      differentiation. Conversely, the treatment of BDL PMF with the PERK inhibitor
      GSK2656157 reduced ER stress, which caused a decrease in their angiogenic
      properties, and restored their proliferative and migratory capacity. In
      conclusion, PMF develop ER stress as they expand with the progression of
      fibrosis, which further increases their proangiogenic activity, but also inhibits
      their proliferation and migration. This phenotypic switch may restrict PMF
      expansion while they support angiogenesis.

PMID- 30292634
TI  - IL-23 production of liver inflammatory macrophages to damaged hepatocytes
      promotes hepatocellular carcinoma development after chronic hepatitis B virus
      infection.
AB  - Liver inflammation after chronic hepatitis B virus (HBV) infection is essential
      for hepatocellular carcinoma (HCC) development. We did a nested case-control
      study based on QBC chronic HBV infection cohort to identify HCC-related
      inflammatory cytokines. Serum levels of distinct Th-cell representative cytokines
      at varied periods before HCC diagnosis were determined in 50 HCC cases and 150
      age- and gender-matched controls who did not develop HCC in 8-10 years. The
      individuals with HCC outcome had statistically higher serum levels of IL-23 than
      controls (P < 0.01). Further analysis in HCC tissues showed that CD14+
      inflammatory macrophages were the major IL-23 producers. Monocytes-derived
      macrophages generated more amount of IL-23 after being stimulated with cell
      associated HBV core antigen from damaged HBV-infected hepatocytes than the cells
      being stimulated with HBV-S and HBV e antigen, which are secreted from infected
      hepatocytes. IL-23 upregulated IL-23 receptor expressions on macrophages,
      enhanced macrophage-mediated angiogenesis. In HBV-transgenic (Alb1HBV) mice,
      administration of diethylnitrosamine induced more liver tumors than in wild-type
      mice. The livers of Alb1HBV mice had higher concentrations of IL-23 and vascular
      endothelial growth factor (VEGF) than the wild-type mice. Neutralizing IL-23
      activity, diethylnitrosamine-treated Alb1HBV mice developed significantly less
      tumors and produced less VEGF, tumor angiogenesis was inhibited with dramatically
      decreased CD31+ cells within tumor mass (all P < 0.01). CONCLUSION: Persistent IL
      23 generation of liver inflammatory macrophages responding to damaged hepatocytes
      after chronic HBV infection altered macrophage function for HCC promotion.
      Blocking IL-23 activity might be helpful for the intervention in chronic
      hepatitis B patients who had high risk to HCC.

PMID- 30292636
TI  - mTOR inhibitor INK128 attenuates systemic lupus erythematosus by regulating
      inflammation-induced CD11b+Gr1+ cells.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by
      systemic chronic inflammation that can affect multiple major organ systems.
      Although the etiology of SLE is known to involve a variety of factors such as the
      environment, random factors and genetic susceptibility, the exact role of
      CD11b+Gr1+ myeloid cells in lupus progression is not fully understood. Myeloid
      derived CD11b+Gr1+ cells are thought to be a heterogeneous group of immature
      myeloid cells with immune function. Some studies have reported that CD11b+Gr1+
      cells and the activation of mTOR pathway are involved in the pathogenesis of
      systemic lupus erythematosus (SLE). However, it is still not clarified about the
      mechanism of influence of lupus microenvironment and mTOR signaling on CD11b+Gr1+
      cells. In the present study, we found that the percentage of CD11b+Gr1+ cells
      increased prior to the abnormal changes of Th17, Treg, T and B cells during lupus
      development. TLR7 and IFN-alpha signaling synergized to promote CD11b+Gr1+ cell
      accumulation in an mTOR-dependent manner. Moreover, compared to a traditional
      mTOR inhibitor, INK128 inhibited more effectively the disease activity via
      regulating CD11b+Gr1+ cell expansion and functions. Furthermore, TLR7/IFN-alpha
      modified CD11b+Gr1+ cells promoted unbalance of Th17/Tregs and were inclined to
      differentiate into macrophages via the mTOR pathway. In conclusion, CD11b+Gr1+
      cells increased in the early stages of the lupus progression and mTOR pathway was
      critical for CD11b+Gr1+ cells in lupus development, suggesting the changes of
      inflammation-induced CD11b+Gr1+ cells initate lupus development. We also provide
      evidence for the first time that INK128, a second generation mTOR inhibitor, has
      a good therapeutic action on lupus development by regulating CD11b+Gr1+ cells.

PMID- 30292635
TI  - Differential expression of tumor-associated genes and altered gut microbiome with
      decreased Akkermansia muciniphila confer a tumor-preventive microenvironment in
      intestinal epithelial Pten-deficient mice.
AB  - Phosphatase and tensin homolog (Pten) antagonizes PI3K-Akt signaling; therefore,
      Pten impairment causes tumorigenesis. However, the correlation between Pten
      deficiency and colon cancer has remained elusive due to numerous opposite
      observations. To study this correlation, we examined whether Pten deficiency in
      intestinal epithelial cells (IECs) induces tumorigenesis. With mucosal biopsies
      of human colon cancer and normal colon, Pten mRNA was evaluated by quantitative
      PCR. Using IEC-specific Pten knockout mice (PtenDeltaIEC/DeltaIEC), we examined
      the mitotic activity of IECs; and PtenDeltaIEC/DeltaIEC; Apcmin/+ mice were
      generated by combining PtenDeltaIEC/DeltaIEC with Apcmin/+ mice. Tumor-associated
      gene was evaluated by micro-array analysis. Fecal microbiome was analyzed through
      16S rRNA gene sequencing. We found that Pten mRNA level was reduced in human
      colon cancer relative to normal tissues. Augmented chromatids, increased Ki-67
      and PCNA expression, and enhanced Akt activation were identified in IECs of
      PtenDeltaIEC/DeltaIEC mice compared to Pten+/+ littermate. Combining
      PtenDeltaIEC/DeltaIEC with Apcmin/+ condition caused rapid and aggressive
      intestinal tumorigenesis. However, PtenDeltaIEC/DeltaIEC mice did not develop any
      tumors. While maintaining the tumor-driving potential, these data indicated that
      IEC-Pten deficiency alone did not induce tumorigenesis in mice. Furthermore, the
      expression of tumor-promoting and tumor-suppressing genes was decreased and
      increased, respectively, in the intestine of PtenDeltaIEC/DeltaIEC mice compared
      to controls. The abundance of Akkermansia muciniphila, capable of inducing
      chronic intestinal inflammation, was diminished in PtenDeltaIEC/DeltaIEC mice
      compared to controls. These findings suggested that altered tumor-associated gene
      expression and changed gut microbiota shape a tumor-preventive microenvironment
      to counteract the tumor-driving potential, leading to the tumor prevention in
      PtenDeltaIEC/DeltaIEC mice.

PMID- 30292637
TI  - Intracellular cholesterol accumulation and coenzyme Q10 deficiency in Familial
      Hypercholesterolemia.
AB  - Familial Hypercholesterolemia (FH) is an autosomal co-dominant genetic disorder
      characterized by elevated low-density lipoprotein (LDL) cholesterol levels and
      increased risk for premature cardiovascular disease. Here, we examined FH
      pathophysiology in skin fibroblasts derived from FH patients harboring
      heterozygous mutations in the LDL-receptor. Fibroblasts from FH patients showed a
      reduced LDL-uptake associated with increased intracellular cholesterol levels and
      coenzyme Q10 (CoQ10) deficiency, suggesting dysregulation of the mevalonate
      pathway. Secondary CoQ10 deficiency was associated with mitochondrial
      depolarization and mitophagy activation in FH fibroblasts. Persistent mitophagy
      altered autophagy flux and induced inflammasome activation accompanied by
      increased production of cytokines by mutant cells. All the pathological
      alterations in FH fibroblasts were also reproduced in a human endothelial cell
      line by LDL-receptor gene silencing. Both increased intracellular cholesterol and
      mitochondrial dysfunction in FH fibroblasts were partially restored by CoQ10
      supplementation. Dysregulated mevalonate pathway in FH, including increased
      expression of cholesterogenic enzymes and decreased expression of CoQ10
      biosynthetic enzymes, was also corrected by CoQ10 treatment. Reduced CoQ10
      content and mitochondrial dysfunction may play an important role in the
      pathophysiology of early atherosclerosis in FH. The diagnosis of CoQ10 deficiency
      and mitochondrial impairment in FH patients may also be important to establish
      early treatment with CoQ10.

PMID- 30292638
TI  - The deficiency of macrophage erythropoietin signaling contributes to delayed
      acute inflammation resolution in diet-induced obese mice.
AB  - Obesity has been linked with altered acute inflammation resolution which
      contributes to obesity-related clinical complications; however, the mechanisms
      that contribute to obesity-related unresolved inflammation are not fully known.
      Here we demonstrated that the deficiency of macrophage erythropoietin (EPO)
      signaling contributed to delayed acute inflammation resolution in diet-induced
      obese mice. In zymosan-induced acute peritonitis, in line with the delayed
      resolution of inflammation, the induction of macrophage EPO signaling was
      significantly reduced in obese mice relative to normal mice. Exogenous EPO
      induced macrophage EPO signaling and promoted acute inflammation resolution in
      obese mice. Efferocytosis of apoptotic cells by macrophages which is central in
      inflammation resolution was impaired in obese mice and restored by exogenous EPO.
      Mechanistically, macrophage peroxisome proliferator-activated receptor-gamma
      (PPARgamma) was greatly reduced in obese mice and EPO increased macrophage
      PPARgamma to promote efferocytosis in obese mice. Together, our results identify
      an important mechanism underlying aberrant acute inflammation resolution in
      obesity, with important implications for regulating unresolved acute inflammation
      and normalizing macrophage defects in obese and diabetic individuals.

PMID- 30292639
TI  - Corrigendum to "CHST3 and CHST13 polymorphisms as predictors of bosentan-induced
      liver toxicity in Japanese patients with pulmonary arterial hypertension"
      [Pharmacol. Res. 135 (2018) 259-264].

PMID- 30292640
TI  - HIV-1 Latency Is Maintained by the Estrogen Receptor.
AB  - Persistence of the latent reservoir remains a challenge to curing HIV infection.
      Using shRNA screening, new insights into the molecular mechanisms underlying
      latency regulation indicate that the estrogen receptor is a potent repressor of
      proviral reactivation and may serve as a promising therapeutic target in
      combination with other latency-reversing agents.

PMID- 30292641
TI  - Oesophageal cicatricial pemphigoid.

PMID- 30292642
TI  - Translation and Validation of the Multidimensional Dyspnea-12 Questionnaire.

PMID- 30292643
TI  - Diagnosis and management of pancreatic cancer in adults: A summary of guidelines
      from the UK National Institute for Health and Care Excellence.
AB  - To enable standardisation of care of pancreatic cancer patients and facilitate
      improvement in outcome, the United Kingdom's National Institute for Health and
      Care Excellence (NICE) developed a clinical guideline for the diagnosis and
      management of pancreatic cancer in adults. Systematic literature searches,
      systematic review and meta-analyses were undertaken. Recommendations were drafted
      on the basis of the group's interpretation of the best available evidence of
      clinical and cost effectiveness. There was patient involvement and public
      consultation. Recommendations were made on: diagnosis; staging; monitoring of
      inherited high risk; psychological support; pain; nutrition management; and the
      specific management of people with resectable-, borderline-resectable- and
      unresectable-pancreatic cancer. The guideline committee also made recommendations
      for future research into neoadjuvant therapy, cachexia interventions, minimally
      invasive pancreatectomy, pain management and psychological support needs. These
      NICE guidelines aim to promote best current practice and support and stimulate
      research and innovation in pancreatic cancer.

PMID- 30292644
TI  - Organotypic slice cultures of pancreatic ductal adenocarcinoma preserve the tumor
      microenvironment and provide a platform for drug response.
AB  - BACKGROUND: /Objective: The conventional models currently used to evaluate
      various anti-tumor therapeutic agents are not sufficient for representing human
      pancreatic ductal adenocarcinoma (PDA), which has a unique tumor
      microenvironment. We aimed to produce an organotypic slice culture model from
      human PDA that resembles the in vivo situation and to evaluate the responses of
      PDA slices to established cytotoxic drugs. METHODS: PDA tissues were obtained
      from 10 patients who underwent pancreatic resection. The tissues were sliced by a
      vibratome, and the tumor slices were then cultured. The viability of tumor slices
      during slice culture was evaluated using H&E and immunohistochemical staining,
      and stromal cells were demonstrated. The effects of cytotoxic drugs on PDA cell
      lines and slices were analyzed. RESULTS: Tumor slices maintained their surface
      areas and tissue viability for at least five days during culture. Preserved
      proliferation and apoptosis in tumor slices were observed by the expression of Ki
      67 and cleaved caspase-3. Stromal cells including macrophages (CD68+ and CD163+),
      T cells (CD3+, CD8+, and FOXP3+), and myeloid cells (CD11b+) were present
      throughout the culture period. Staurosporine, gemcitabine, and cisplatin
      treatment of PDA cell lines and tumor slices exerted proportional cytotoxic
      effects in terms of MTT viability, tumor cell number, and Ki-67 and cleaved
      caspase-3 expression. CONCLUSIONS: Organotypic human PDA slice cultures preserved
      their viability and tumor microenvironment for at least five days during slice
      culture. PDA slice culture appears to be a feasible preclinical test model to
      assess the response to anti-tumor agents.

PMID- 30292645
TI  - Perceived control and quality of life among recipients of implantable
      cardioverter defibrillator.
AB  - BACKGROUND: Perceived control is strongly associated with health-related quality
      of life (HRQOL) among patients with chronic conditions, and it is possible to
      increase perceived control with appropriate intervention. Little is known about
      the relationship between perceived control and HRQOL in implantable cardioverter
      defibrillator (ICD) recipients. OBJECTIVES: To determine the relationship of
      perceived control with quality of life in ICD recipients and to determine
      predictors of perceived control in this population. METHODS: A total of 263 ICD
      recipients (63% male, age 61 +/- 14 years) completed the Control Attitude Scale
      Revised to measure perceived control and completed self-reported measures on
      potential correlates of perceived control (i.e., depressive symptoms, anxiety,
      social support, and ICD concerns). The EuroQol-5D was used to measure HRQOL.
      Regression analysis was used to determine predictors of perceived control and its
      relationship to HRQOL, controlling for covariates. RESULTS: Lower perceived
      control (beta = 0.30, p < .01), and higher levels of depression (beta = -0.30, p
      < .01) and anxiety (beta = -0.18, p < .05) predicted lower levels of HRQOL.
      Higher anxiety (beta = -0.17, p < .05), higher depression (beta = -0.23, p <
      .05), lower social support (beta = 0.26, p < .01), and higher ICD-related
      concerns (beta = -0.16, p < .05) independently predicted lower perceived control.
      CONCLUSIONS: Interventions targeting patients' ICD concerns and psychosocial
      factors before, and continuing after, ICD insertion are needed to improve ICD
      recipients' perceived control and, in turn, their HRQOL.

PMID- 30292646
TI  - Upregulation of miR-132 contributes to the pathophysiology of COPD via targeting
      SOCS5.
AB  - The role of microRNAs has been recently identified in chronic obstructive
      pulmonary disease (COPD). This study aimed to examine the role of miR-132 in the
      pathophysiology of COPD and to explore the underlying molecular mechanisms of miR
      132 in COPD. MiR-132 and suppressor of cytokine signaling 5 (SOCS5) mRNA
      expression were detected by qRT-PCR. The number of CD4+ and CD8+ T cells was
      analyzed by flow cytometry. SOCS5 and epidermal growth factor receptor (EGFR)
      protein levels were determined by western blot. Interleukin-1beta (IL-1beta) and
      tumor necrosis factor-alpha (TNF-alpha) concentrations were measured by ELISA.
      MiR-132 expression was up-regulated in the serum from COPD patients and smokers
      compared with nonsmoker controls. The number of CD8+ T cells was significantly
      increased in the serum from COPD patients and smokers. MiR-132 expression was
      negatively correlated with FEV1/FVC%, and positively correlated with CD8+ T cells
      (%). MiR-132 overexpression repressed SOCS5 expression via directly targeting
      SOCS5 3'UTR in human monocyte-like cells (THP-1), which was confirmed by
      luciferase reporter assay. MiR-132 overexpression increased EGFR protein levels
      and the concentrations of inflammatory cytokines (IL-1beta and TNF-alpha) in THP
      1 cells, and these effects were attenuated by enforced expression of SOCS5.
      Further, cigarette smoke extract (CSE) treatment up-regulated miR-132 expression,
      down-regulated SOCS5 expression, and increased inflammatory cytokines levels,
      which was attenuated by miR-132 knockdown in THP-1 cells. Consistent findings
      were also found in the human bronchial epithelial cells (BEAS-2B). Collectively,
      our data implicated that miR-132 may promote inflammation in THP-1 and BEAS-2B
      cells at least via targeting SOCS5 in COPD.

PMID- 30292647
TI  - Structural and functional profiles of the gut microbial community in polycystic
      ovary syndrome with insulin resistance (IR-PCOS): a pilot study.
AB  - Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder
      that affects 9-21% of reproductive-aged women. Affected women frequently display
      obesity, insulin resistance, and inflammation. Altered gut microbial community
      has been reported in PCOS and obese PCOS patients. However, the profile of the
      gut microbial community in insulin resistant PCOS (IR-PCOS) patients still
      remains unknown. In this study, next-generation sequencing based on the 16S rRNA
      gene was used to compare the gut microbial composition of women with IR-PCOS (n =
      9, PCOS with insulin resistance), NIR-PCOS (n = 8, PCOS alone) and healthy
      controls (n = 8, HC). We assessed that the composition of the gut microbial
      communities in NIR-PCOS and IR-PCOS patients were significantly altered. The
      family Bacteroidaceae was prolific in the NIR-PCOS group and reached its highest
      level in the IR-PCOS group, while the Prevotellaceae dramatically decreased in
      PCOS patients, especially in the IR-PCOS group. Subsequent correlation analysis
      revealed that the increased clinical parameter levels, including insulin
      resistance, sex-hormones and inflammation, were positively associated with the
      abundance of Bacteroidaceae, but negatively associated with that of
      Prevotellaceae. In addition, IR-PCOS patients also displayed a significant
      difference in their amounts of Ruminococcaceae and Lachnospiraceae when compared
      to the NIR-PCOS group. Moreover, the functional prediction from PICRUSt revealed
      that 73 pathways are significantly changed in the gut microbial communities of
      PCOS patients. Specifically, 21 metabolism-associated pathways, including the
      steroid hormone biosynthesis and lipopolysaccharide biosynthesis pathways, are
      obviously changed in IR-PCOS when compared to NIR-PCOS and HC groups. Taking this
      into consideration, our present study suggests that the dysbiosis of gut
      microbial communities occurred most notably in IR-PCOS patients, and the
      difference in gut dysbiosis profile between the IR-PCOS and NIR-PCOS should be
      considered in clinical treatment for PCOS patients and future drugs development.

PMID- 30292648
TI  - Metabolic comparison of one-anastomosis gastric bypass, single-anastomosis
      duodenal-switch, Roux-en-Y gastric bypass, and vertical sleeve gastrectomy in
      rat.
AB  - BACKGROUND: One-anastomosis gastric bypass (OAGB) and single-anastomosis duodenal
      switch (SADS) have become increasingly popular weight loss strategies. However,
      data directly comparing the effectiveness of these procedures with Roux-en-Y
      gastric bypass (RYGB) and vertical sleeve gastrectomy (SG) are limited.
      OBJECTIVES: To examine the metabolic outcomes of OAGB, SADS, RYGB, and SG in a
      controlled rodent model. SETTING: Academic research laboratory, United States.
      METHODS: Surgeries were performed in diet-induced obese Long-Evans rats, and
      metabolic outcomes were monitored before and for 15 weeks after surgery. RESULTS:
      All bariatric procedures induced weight loss compared with sham that lasted
      throughout the course of the study. The highest percent fat loss occurred after
      OAGB and RYGB. All bariatric procedures had improved glucose dynamics associated
      with an increase in insulin (notably OAGB and SADS) and/or glucagon-like protein
      1 secretion. Circulating cholesterol was reduced in OAGB, SG, and RYGB. OAGB and
      SG additionally decreased circulating triglycerides. Liver triglycerides were
      most profoundly reduced after OAGB and RYGB. Circulating iron levels were
      decreased in all surgical groups, associated with a decreased hematocrit value
      and increased reticulocyte count. The fecal microbiome communities of OAGB, SADS,
      and RYGB were significantly altered; however, SG exhibited no change in
      microbiome diversity or composition. CONCLUSIONS: These data support the use of
      the rat for modeling bariatric surgical procedures and highlight the ability of
      the OAGB to meet or exceed the metabolic improvements of RYGB. These data point
      to the likelihood that each surgery accomplishes metabolic improvements through
      both overlapping and distinct mechanisms and warrants further research.

PMID- 30292649
TI  - Sexual Health Education for Adolescent Males Who Are Interested in Sex With
      Males: An Investigation of Experiences, Preferences, and Needs.
AB  - PURPOSE: There is a dearth of research to inform sexual education programs to
      address sexual health disparities experienced by adolescent males who are
      interested in sex with males (AMSM). The current study sought to determine where
      AMSM receive sexual health information, clarify their preferences, and explore
      relations with sexual behavior. METHODS: AMSM (N = 207; ages 14-17) in the United
      States completed an online sexual health survey. Bivariate associations between
      sexual education exposure/preferences by sexual behavior were assessed using
      Fisher's exact tests and one-way analyses of variance. RESULTS: Eighty-nine (43%)
      participants reported no sexual contact with male partners, 77 (37%) reported
      sexual contact without condomless anal sex, and 41 (20%) reported condomless anal
      sex. Participants received sexual health information from their parents/guardians
      (n = 122, 59%), formal sources (n = 160, 78%), and the Internet (n = 135, 65%).
      The most commonly covered topics by parents/guardians and formal sources were how
      to say no to sex, how to prevent HIV and other sexually transmitted infections,
      and methods of birth control. The most common online-researched topics were how
      to safely have anal sex, the types of sex you can have with a male partner, how
      to use a condom, and how to use lubrication. Participants noted preferring a
      sexually-explicit online sexual health program that addresses male-male sex.
      CONCLUSIONS: Online sexual education programs that explicitly address male-male
      sex are needed. Tailored programs can help AMSM develop healthy sexual behaviors
      and decrease their HIV/STI risk.

PMID- 30292650
TI  - Endocrine and psychological stress response in simulated doctor-patient
      interactions in medical education.
AB  - BACKGROUND: Training of doctor-patient interactions by means of patient actors is
      considered a useful didactic tool in medical education. However, though students
      report it as being highly stressful little systematic research has verified this
      notion. AIMS: To assess the endocrine and psychological stress responses of
      students in the doctor vs. the observer role in simulated doctor-patient
      interactions. METHODS: Salivary cortisol and anxiety was assessed in N = 86
      participants of a mandatory course on doctor-patient interactions on three
      consecutive days. During two of these days they were in the observer role and
      gave feedback to another student and on one of these days they were in the doctor
      role and were being given feedback. Saliva was sampled at 4 points in time per
      day: prior to interaction (T1); after watching the video of the interaction (T2);
      after feedback (T3); after observation of another interaction (T4). Assessments
      on observer days took place at the respective time points and at the same time of
      the day. 3-way mixed ANOVAs were computed with the factors "day of data sampling"
      (F1); "day with doctor role" (F2); "measurement time"(F3). RESULTS: Significant
      two-way interactions F1 * F2 and three-way interactions F1 * F2 * F3 were
      observed both for cortisol and for anxiety (all p < .001). Neither cortisol nor
      anxiety were related to task severity. Anxiety at T1 correlated with cortisol
      increase from T1 to T2 (r = .266; p = .013). DISCUSSION: Results confirm that
      playing the doctor role in a simulated doctor-patient interaction represents a
      significant stressor in medical students. Effect sizes considerably exceed those
      observed in laboratory stress. This brings about new questions regarding
      moderating factors, effects of repetitions and relationship to medical
      performance. The ecological validity of this stressor can also make it a useful
      tool in basic endocrine research.

PMID- 30292651
TI  - Genetic variation of the mineralocorticoid receptor gene (MR, NR3C2) is
      associated with a conceptual endophenotype of "CRF-hypoactivity".
AB  - Recently, the "conceptual endophenotype" approach has been proposed as a means to
      identify subgroups of patients affected by stress-related psychiatric disorders.
      Conceptual endophenotypes consist of patterns of psychological, biological, and
      symptomatic elements. We studied a sample of patients seeking help for
      psychosomatic and stress-related disorders (total N = 469), who were evaluated
      with a diagnostic instrument that integrates psychological and biological data to
      derive 13 endophenotypes, or Neuropattern. The goal of this study was to explore
      associations between common variations of the mineralocorticoid receptor gene
      (MR, NR3C2), and the 13 conceptual endophenotypes of Neuropattern, as well as
      with the respective biological and symptom measures. A common haplotype of the
      MR, comprised of two functional single nucleotide polymorphism (rs2070951 G/C &
      rs5522 A/G), was associated with the conceptual endophenotype CRF-hypoactivity,
      characterized by low cortisol levels at awakening and a symptom constellation
      often observed in atypical depression. Homozygous carriers of the G-A haplotype
      (haplotype 1), previously associated with reduced dispositional optimism,
      increased levels of rumination and higher risk for depression, more frequently
      endorsed this Neuropattern. In addition to the overall association between MR
      variation and CRF hypoactivity, we observed in the whole sample significant
      associations between MR haplotypes and cortisol awakening response patterns, as
      well as with symptoms that characterize the CRF hypoactivity endophenotype. If
      replicated, MR haplotype 1 might serve as a vulnerability marker for a disorder
      class characterized in biological terms by reduced cortisol levels, and in terms
      of symptom constellation by features often observed in atypical depression.

PMID- 30292652
TI  - The investigation of the pyrethroid insecticide lambda-cyhalothrin (LCT)-affected
      Ca2+ homeostasis and -activated Ca2+-associated mitochondrial apoptotic pathway
      in normal human astrocytes: The evaluation of protective effects of BAPTA-AM (a
      selective Ca2+ chelator).
AB  - Exposure to insecticides has been found to have deleterious effects on human
      health. Lambda-cyhalothrin (LCT), a mixture of isomers of cyhalothrin, is a
      pyrethroid insecticide routinely used in pest control programs. LCT was reported
      to cause neurotoxic effects in various models. However, the mechanism of
      underlying effect of LCT on cytotoxicity in normal human brain cells is still
      elusive. This study examined whether LCT affected Ca2+ homeostasis and Ca2+
      related physiology in Gibco(r) Human Astrocytes (GHA cells), and explored whether
      BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid), a selective
      Ca2+ chelator, has protective effects on LCT-treated GHA cells. The data show
      that LCT (10-15 MUM) concentration-dependently induced cytotoxicity in both GHA
      cells and DI TNC1 normal rat astrocytes but only induced intracellular Ca2+
      concentration ([Ca2+]i) rises in GHA cells. In terms of Ca2+ signaling in GHA
      cells, LCT-induced [Ca2+]i rises were reduced by removing extracellular Ca2+ and
      were inhibited by store-operated Ca2+ channel modulators (2-APB, econazole or
      SKF96365). In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+
      pump inhibitor thapsigargin abolished LCT-induced [Ca2+]i rises. Conversely,
      incubation with LCT abolished thapsigargin-induced [Ca2+]i rises. Regarding
      cytotoxicity, LCT evoked apoptosis by regulating apoptotic protein expressions
      (Bax, BCl-2, cleaved caspase-9/-3). This apoptotic response was significantly
      inhibited by prechelating cytosolic Ca2+ with BAPTA-AM. Together, in GHA cells,
      LCT induced [Ca2+]i rises by inducing Ca2+ entry via store-operated Ca2+ channels
      and Ca2+ release from the endoplasmic reticulum. Moreover, BAPTA-AM has a
      protective effect on inhibiting LCT-activated mitochondrial apoptotic pathway.
      This study provided new insights into the molecular protective mechanism of LCT
      induced cytotoxicity in normal human astrocytes.

PMID- 30292653
TI  - Differential copper-induced death and regeneration of olfactory sensory neuron
      populations and neurobehavioral function in larval zebrafish.
AB  - Fish rely heavily on their sense of smell to maintain behaviors essential for
      survival, such as predator detection and avoidance, prey selection, social
      behavior, imprinting, and homing to natal streams and spawning sites. Due to its
      direct contact with the outside environment, the peripheral olfactory system of
      fish is particularly susceptible to dissolved contaminants. In particular,
      environmental exposures to copper (Cu) can cause a rapid loss of olfactory
      function. In this study, confocal imaging of double-transgenic zebrafish larvae
      with differentially labeled ciliated and microvillous olfactory sensory neurons
      (OSNs) were used to examine cell death and regeneration following Cu exposure.
      Changes in cell morphologies were observed at varying degrees within both
      ciliated and microvillous OSNs, including the presence of round dense cell
      bodies, cell loss and fragmentation, retraction or loss of axons, disorganized
      cell arrangements, and loss of cells and fluorescence signal intensity, which are
      all indicators of cell death after Cu exposure. A marked loss of ciliated OSNs
      relative to microvillous OSNs occurred after exposure to low Cu concentrations
      for 3 h, with some regeneration observed after 72 h. At higher Cu concentrations
      and 24-h exposures, ciliated and microvillous OSNs were damaged with increased
      severity of injury with longer Cu exposures. Interestingly, microvillous, but not
      ciliated OSNs, regenerated rapidly within the 72-h time period of recovery after
      death from Cu exposure, suggesting that microvillous OSNs may be replaced in lieu
      of ciliated OSNs. An increase in bromodeoxyuridine labeling was observed 24 h
      after Cu-induced OSN death, suggesting that increased proliferation of the
      olfactory stem cells replaced the damaged OSNs. Olfactory behavioral analyses
      supported our imaging studies and revealed both initial loss and restoration of
      olfactory function after Cu exposures. In summary, our studies indicate that
      following zebrafish OSN damage by Cu, regeneration of microvillous OSNs may occur
      exceeding ciliated OSNs, likely via increased proliferation of the cellular
      reservoir of neuronal OSC precursors. Transgenic zebrafish are a valuable tool to
      study metal olfactory injury and recovery and to characterize sensitive olfactory
      neuron populations in fish exposed to environmental pollutants.

PMID- 30292654
TI  - Prenatal exposure to organochlorine pesticides and early childhood communication
      development in British girls.
AB  - BACKGROUND: The developing brain is susceptible to exposure to neurodevelopmental
      toxicants such as pesticides. AIMS: We explored associations of prenatal serum
      concentrations of hexachlorobenzene (HCB), beta-Hexachlorocyclohexane (beta-HCH),
      2,2-Bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE) and 2,2-Bis(4-chlorophenyl
      1,1,1-trichloroethane (p,p'-DDT) with maternal-reported measures of verbal and
      non-verbal communication in young girls. STUDY DESIGN AND METHODS: We studied a
      sample of 400 singleton girls and their mothers participating in the Avon
      Longitudinal Study of Parents and Children (ALSPAC) using multivariable linear
      regression models adjusting for parity, Home Observation Measurement of the
      Environment (HOME) score, maternal age and education status, and maternal tobacco
      use during the first trimester of pregnancy. EXPOSURE AND OUTCOME MEASURES:
      Maternal serum samples (collected at median 15 wks. gestation [IQR 10, 28]) were
      assessed for selected organochlorine pesticide levels. Communication was assessed
      at 15 and 38 months, using adapted versions of the MacArthur Bates Communicative
      Development Inventories for Infants and Toddlers (MCDI). RESULTS: At 15 months,
      girls born to mothers with prenatal concentrations of HCB in the highest tertile
      had vocabulary comprehension and production scores approximately 16% (p = 0.007)
      lower than girls born to mothers with concentrations in the lowest tertile. This
      association varied by maternal parity in that the evidence was stronger for
      daughters of nulliparous mothers. At 38 months, girls born to mothers with
      prenatal concentrations of HCB in the highest tertile had mean adjusted
      intelligibility scores that were 3% (p = 0.03) lower than those born to mothers
      with concentrations in the lowest tertile; however, results did not vary
      significantly by parity. Maternal concentrations of beta-HCH and p,p'-DDE were
      not significantly associated with MCDI scores at 15 or 36 months. p,p'-DDT had an
      inconsistent pattern of association; a significant positive association was
      observed between p,p'-DDT with verbal comprehension scores at 15 months; however,
      at 38 months a significant inverse association was observed for p,p'-DDT with
      communicative scores. This inverse association for p,p'-DDT among older girls
      tended to be stronger among daughters of mothers who had lower depression scores.
      CONCLUSIONS: Organochlorine pesticide exposure in utero may affect communication
      development.

PMID- 30292655
TI  - Fluid-fluid level in postpartum pituitary microadenoma necrosis on MRI.

PMID- 30292656
TI  - Knee crepitus is not associated with the occurrence of total knee replacement in
      knee osteoarthritis - a longitudinal study with data from the Osteoarthritis
      Initiative.
AB  - OBJECTIVE(S): To investigate whether the presence of knee crepitus is associated
      with the occurrence of total knee replacement (TKR), quality of life and deficits
      in physical function at long-term. METHODS: Setting - This observational study
      uses longitudinal data (up to 4-year follow-up) from the Osteoarthritis
      Initiative (OAI). Participants - 4566 participants. Main Outcome Measure(s) -
      Logistic regression models were used to test if baseline knee crepitus is
      associated with the occurrence of TKR. Linear mixed models with adjustment for
      confounding variables (age, gender, BMI and Kellgren-Lawrence grade) were used to
      test the association between baseline knee crepitus and longitudinal changes in
      the pain, self-reported physical function, quality of life and performance-based
      function. RESULTS: The presence of knee crepitus at baseline does not predict the
      occurrence of TKR at 36 months (p=0.58 and 0.67 for right and left knees,
      respectively). The crepitus group presented a slightly knee extension strength
      decline from baseline to 48 months (p=0.03 for the right and 0.01 for the left
      knee; between group difference=2% for both right [95%CI=-0.12; -0.01] and left
      knees [95%CI=-0.13; -0.02]). CONCLUSION: The presence of knee crepitus is not
      associated with the occurrence of TKR in the following three years. Knee crepitus
      is associated with slightly declines in knee extension strength, but this does
      not seem to affect physical function and quality of life at long-term.

PMID- 30292658
TI  - Patients' expectations and satisfaction in subthalamic nucleus deep brain
      stimulation for Parkinson disease: 6-year follow-up.
AB  - OBJECTIVE: Patients' expectations are considered to play an important role in STN
      DBS. We explored the relationship between expectations, satisfaction and outcome
      6 years after surgery. METHODS: 15 patients with Parkinson disease (9 males, mean
      age 60.5 +/- 6.4 years) undergoing STN DBS completed a modified PDQ-39
      questionnaire (incorporating an assessment of patients' expected changes in
      addition to the standard quality of life items) preoperatively and at 6 years
      postoperatively. A satisfaction questionnaire accompanied the postoperative
      questionnaire. RESULTS: At 6 years follow-up, PDQ-39 scores were unchanged from
      preoperative scores except in the stigma domain which showed a significant
      improvement. There was no significant difference between the postoperatively
      rated expected PDQ-39 summary score and the postoperative actual PDQ-39 summary
      score. However, there was a significant difference between the preoperatively
      rated expected PDQ-39 summary score and the postoperative actual PDQ-39 summary
      score. Patients remained highly satisfied with the outcome of surgery (mean
      satisfaction score 83%). Satisfaction did not correlate with PDQ-39 summary
      scores, domain scores or fulfilment of expectations. The more satisfied patients
      (satisfaction >= 80%) changed their expectations so that their postoperatively
      rated expectations reflected a less favorable condition whereas no such change
      was seen in the less satisfied (satisfaction < 80%) patients. CONCLUSIONS:
      Patients remain highly satisfied with STN DBS 6 years after surgery although
      quality of life assessed by the PDQ-39 may return to baseline levels. Patients'
      expectations change over time and may influence patient satisfaction. Managing
      expectations before and after surgery plays an essential role in STN DBS.

PMID- 30292657
TI  - Long-Term Results After Endoscopic Resection of Colloid Cysts.
AB  - BACKGROUND: Endoscopic resection of colloid cysts is a widely accepted treatment
      option instead of microsurgery. However, there is still a debate about a
      potentially higher rate of incomplete resections and recurrence. OBJECTIVE: The
      aim of this retrospective study was to evaluate long-term results after
      endoscopic removal of colloid cysts. METHODS: Twenty patients underwent
      endoscopic treatment in our department. Eighteen patients agreed to follow-up
      examinations. In 17 patients, magnetic resonance images were obtained. RESULTS:
      Total cyst resection was achieved in 16 procedures. In 1 patient, only plexus
      coagulation and widening of the ipsilateral foramen of Monro were performed. In 3
      patients, small remnants of the cyst membrane were left behind. Conversion to
      microsurgery became necessary in 1 patient. Mild temporary complications occurred
      in 6 patients. Preoperative symptoms were completely relieved in 16 patients and
      improved in 2 patients. The average follow-up period was 188 months. In the
      patient with plexus coagulation, the cyst did not change. Recurrence occurred in
      2 of 3 patients with cyst remnants. To date, no cyst remnant or recurrence has
      caused any symptoms or required surgical treatment. CONCLUSIONS: Our results
      indicate that endoscopic treatment of colloid cysts is a safe and effective
      treatment option that provides excellent long-term results. However, we
      determined that a significant risk for recurrence exists when even small parts of
      the cyst capsule were left behind. Therefore, we advocate an attempt at total
      endoscopic cyst resection.

PMID- 30292659
TI  - Chiari 1 Malformation Surgery: Comparing Non-violation of the Arachnoid versus
      Arachnoid Opening and Thermocoagulation of the Tonsils.
AB  - OBJECTIVE: Evidence is lacking concerning the myriad surgical techniques for type
      1 Chiari malformation. This study evaluated the impact of arachnoid violation
      with tonsil thermocoagulation during surgical craniovertebral junction
      decompression. METHODS: The evaluation included aspects of the neurologic
      examination and parameters of cerebrospinal fluid flow on magnetic resonance
      imaging during preoperative and postoperative periods. All patients underwent
      craniovertebral junction decompression and opening of the dura mater. Patients
      were divided into 2 study groups. Patients in group 1 did not undergo arachnoid
      violation. Patients in group 2 underwent tonsil manipulation and systematic
      opening of the fourth ventricle outlet. RESULTS: There were 16 patients enrolled
      in each group (total of 32 patients). Regarding clinical improvement, there were
      no significant differences between groups in the postoperative period. Group 2
      had more adverse events (relative risk 2.45, 95% confidence interval 1.55-3.86).
      In terms of cerebrospinal fluid flow parameter analyses, patients in group 1
      achieved better results (P < 0.05). CONCLUSIONS: For treatment of symptomatic
      type 1 Chiari malformation, craniovertebral junction decompression with arachnoid
      preservation (i.e., without tonsillar manipulation) seems more suitable than the
      addition of arachnoid opening and thermocoagulation of the tonsils.

PMID- 30292660
TI  - The Need For Grass Root Innovation In Developing Countries: A Case For Stationary
      Binder Clips In Scalp Hemostasis.

PMID- 30292661
TI  - Hemorrhagic Atypical Planum Sphenoidale Meningioma with Intermittent Vision Loss
      A Rare Presentation of Apoplexy.
AB  - BACKGROUND: Symptoms that mimic pituitary apoplexy may be encountered with other
      neoplastic or infectious lesions. CASE DESCRIPTION: This 38-year-old man
      presented with severe sudden-onset headache and relapsing and remitting vision
      loss. Radiographic imaging studies demonstrated radiographic features of a
      hyperdense, hemorrhagic mass in the sellar region. MRI revealed a 4-cm mass
      abutting the optic chiasm and compressing the pituitary. After 4-week follow-up
      surveillance MRI demonstrated near-complete resolution of the previously
      identified planum sphenoidale and suprasellar mass, the patient re-presented 13
      months later with recurrent symptoms. MRI demonstrated recurrence of the mass.
      Given the broad differential diagnosis, an endoscopic endonasal biopsy was
      obtained; the findings were suggestive of a high-grade meningioma. The patient
      underwent elective resection of the extra-axial lesion via a frontotemporal
      approach. The lesion was identified as a hemorrhagic suprasellar atypical planum
      sphenoidale meningioma. Postoperatively, the patient's headaches improved
      significantly and his right-sided visual changes resolved. After adjuvant
      radiotherapy (5400 cGy in 30 fractions) to the surgical cavity 3 months later, at
      last follow-up 5 months postoperatively, the patient was at his neurologic
      baseline and denied any headaches or visual sequelae. CONCLUSIONS: As the most
      common benign intracranial tumors, meningiomas should remain in the differential
      for patients presenting with apoplectiform symptoms.

PMID- 30292662
TI  - Transsphenoidal Approach for Pituitary Adenomas in Elderly Patients.
AB  - INTRODUCTION: With a rapidly expanding elderly population in the United States,
      the incidence of pituitary adenomas in elderly will continue to rise. In this
      study, we aim to evaluate the safety and efficacy of transsphenoidal endoscopic
      endonasal resection for pituitary adenomas in the elderly population. METHODS: A
      retrospective review of 131 consecutive patients who underwent transsphenoidal
      endoscopic endonasal resection for pituitary adenomas at the University of Miami
      Hospital between 2012 and 2016 was performed. Preoperative, intraoperative, and
      surgical outcomes were analyzed in elderly (>70 years) versus nonelderly (<70
      years) patients. RESULTS: Of the 131 patients, 23 of them were >70 years (18%),
      of which 14 were septuagenarians and 9 were octogenarians. Elderly patients were
      more likely to present with vision loss (80.8% vs. 56.6%; P = 0.013) and larger
      tumors on imaging (2.7 +/- 1.0 cm vs. 2.4 +/- 1.3 cm; P = 0.042). Overall
      surgical and endocrinologic outcomes between the 2 groups were similar. However,
      patients <70 years old were more likely to have a gross total resection (86.7%
      vs. 65.4%; P = 0.011), as well as transient diabetes insipidus (54.3% vs. 26.9% P
      = 0.012) and intraoperative cerebrospinal fluid leak (83.5% vs. 58.5%; P =
      0.013). However, permanent postoperative complication rates were similar
      including rate of permanent diabetes insipidus (4.3% elderly vs. 12.1% adult),
      cerebrospinal fluid leak (8.7% elderly vs. 8.4% adult), and meningitis (4.3%
      elderly vs. 2.8% adult). There were no medical complications or deaths in our
      cohort. CONCLUSION: The transsphenoidal endoscopic endonasal approach can be a
      safe and effective technique for resection of pituitary adenomas in patients >70
      years old with appropriate patient selection.

PMID- 30292663
TI  - Biomechanical Study of Novel Unilateral Fixation Combining Unilateral Pedicle and
      Contralateral Translaminar Screws in the Subaxial Cervical Spine.
AB  - INTRODUCTION: In several situations, the stability of the subaxial cervical spine
      is damaged and involves the lateral mass of 1 side; in these cases, a pedicle
      screw (PS) or lateral mass screw (LMS) may not be suitable for placement on the
      affected side. Therefore, salvage short-segment fixation with satisfactory
      stability is needed when bilateral fixation is not feasible. METHODS: Seven fresh
      frozen human cervical spine specimens were used to test the 3-plane range of
      motion (ROM) of the C4-C5 segment. Quasistatic 2-Nm flexibility testing was
      performed in the following sequence: 1) intact; 2) destabilization (using 3
      column injury models) treated with bilateral mass screws (BMSs); 3)
      destabilization treated with a unilateral PS combined with a contralateral
      translaminar screw (UPS+CTLS); and 4) destabilization treated with bilateral PSs
      (BPSs). Then, a pullout strength test was performed for the PSs, LMSs, and
      translaminar screws (TLSs) using 7 isolated C4 and C5 vertebrae. RESULTS: The
      UPS+CTLS group showed no significant difference from the BMS group in the 3-plane
      ROM or from the BPS group in the axial rotation or flexion-extension ROM but
      showed a significantly greater lateral bending ROM than did the BPS group. The
      pullout strength test showed that both C4 and C5 TLSs had strength similar to
      that of LMSs but poorer than that of PSs. CONCLUSIONS: Fixation with the hybrid
      UPS+CTLS construct performed as well as BMS fixation in our biomechanical tests
      and may play a clinical role when BPS or BMS placement is not feasible for short
      segment fixation.

PMID- 30292665
TI  - Hypoxia-Inducible Factor 1alpha and AT-Rich Interactive Domain-Containing Protein
      1A Expression in Pituitary Adenomas: Association with Pathological, Clinical, and
      Radiological Features.
AB  - BACKGROUND: Hypoxia-inducible factor (HIF) plays a major role in tumorigenesis
      and cancer progression. In hypoxic conditions, HIF is upregulated and has been
      shown to activate multiple genes required for cells to adapt to hypoxia. AT-rich
      interactive domain-containing protein 1A (ARID1A), a SWI/SNF (switch/sucrose
      nonfermentable) chromatin remodeling gene has context-dependent tumor-suppressive
      and oncogenic roles in cancer. We assessed the correlations between the
      expression and mutations of HIF1A and ARID1A in histopathologically confirmed
      pituitary adenomas. METHODS: We performed a retrospective analysis of 71 patients
      who had undergone surgery for pituitary adenoma. Patient demographic,
      radiological, and histopathological features were correlated with HIF1A and
      ARID1A expression. RESULTS: Most cases were HIF1A positive (62%). No significant
      correlation was found between HIF1A expression and age, gender, tumor size, bone
      erosion, hemorrhage, or Ki-67 index. An inverse correlation was demonstrated
      between HIF1A and cavernous sinus invasion (P = 0.035). ARID1A loss was found in
      28.2% of pituitary adenomas. No significant correlation was found between ARID1A
      and any of the assessed variables. CONCLUSIONS: In our patient cohort, we found
      that most pituitary adenomas expressed HIF1A. To the best of our knowledge, we
      are the first to assess the presence of ARID1A loss in pituitary adenomas, which
      occurred in 28.2% of cases. No individual demographic, imaging, or
      histopathological feature was predictive of ARID1A. Likewise, with the exception
      of an increased incidence of cavernous sinus invasion, no correlation was found
      with HIF1A. Given the prognostic value of these markers in other malignancies,
      their frequency in pituitary adenomas warrants further exploration of their
      potential role in pituitary adenoma treatment and outcome.

PMID- 30292664
TI  - Disturbed Consciousness and Coma: Diagnosis and Management of Intracranial
      Hypotension Caused by a Spinal Cerebrospinal Fluid Leak.
AB  - OBJECTIVE: The diagnosis and treatment of intracranial hypotension associated
      with a spinal cerebrospinal fluid (CSF) leak, especially in comatose patients,
      have yet to be established. METHODS: Clinical manifestations, neuroimaging
      findings, and treatment outcomes in 11 patients (Glasgow Coma Scale score 10 +/-
      4) were described and compared with 36 patients with normal consciousness.
      RESULTS: Patients with disturbed consciousness were diagnosed at a significantly
      older age (55 +/- 11 years; P < 0.001) than those without (42 +/- 8.8 years).
      Neuroimaging findings in patients with disturbed consciousness were characterized
      by a smaller midbrain-pons angle (7.8 +/- 10 degrees ; P < 0.001), brainstem
      swelling (122%; P = 0.002), and thicker subdural hematomas (16 +/- 7.0 mm degrees
      ; P < 0.001). Epidural blood patch (EBP) alone did not achieve sustained
      improvements in patients with disturbed consciousness but did in most patients
      without (94%; P = 0.001). Over the treatment course, 5 patients progressed to
      coma, which correlated with a high signal intensity on T2-weighted magnetic
      resonance imaging in the brainstem. Hematoma drainage before EBP caused
      neurologic deterioration in 2 patients. Simultaneous EBP after hematoma drainage
      achieved sustained improvements in 5 of 6 patients. Simultaneous microsurgical
      dural repair after hematoma drainage achieved more rapid improvements in 3 of 3
      patients. CONCLUSIONS: Among patients with intracranial hypotension caused by a
      spinal CSF leak, disturbed consciousness may occur in elderly patients because of
      severe diencephalic-mesencephalic deformities. Simultaneous EBP after safe
      hematoma drainage is indicated for these patients. Alternatively, dural repair is
      indicated for patients for whom the spinal level of dural disease has been
      identified. Hematoma drainage before EBP is not recommended because it caused
      deterioration.

PMID- 30292666
TI  - Cord Splitting Access to Ventral Intradural Cysts of Cervicothoracic Junction and
      Thoracic Spine.
AB  - OBJECTIVE: Surgical treatment of ventrally located intradural cysts is difficult
      and controversial. Laminectomy with division of the denticulate ligaments and
      gentle cord mobilization remains the standard approach but risks further
      neurologic deterioration secondary to cord manipulation. Our purpose is to
      evaluate the safety and effectiveness of a midline cord-splitting approach as an
      alternative for treating ventral thoracic intradural cysts. METHODS: We describe
      2 patients who were treated for ventral intradural cysts causing progressive and
      severe myelopathy. Under general anesthesia and continuous neurophysiologic
      monitoring, laminectomy, durotomy, and cord splitting through a midline approach
      gave direct access to both lesions. Cyst drainage was supplemented by a
      cystopleural shunt in 1 case. RESULTS: Cyst collapse and cord reexpansion were
      documented in both patients with a magnetic resonance imaging scan 1 week after
      surgery. In both cases there was a significant neurologic improvement, which was
      maintained 2 years postoperatively. Intraoperative monitoring recorded no loss of
      somatosensory or motor potentials during surgery. Follow-up magnetic resonance
      imaging scans 2 years postoperatively showed no evidence of cyst recurrence, and
      both patients remained neurologically improved and stable. CONCLUSIONS: We have
      been able to drain 2 ventral intradural cysts using a cord-splitting technique.
      This has allowed safe access to purely ventrally located lesions, which were
      inaccessible dorsally or dorsolaterally. By using this method we have been able
      to avoid a more invasive ventral transthoracic approach necessitating
      vertebrectomy and reconstruction and risking serious complications.

PMID- 30292667
TI  - Investigation of the Effect of Alemtuzumab in an Experimental Spinal Cord Trauma
      Model in Rats.
AB  - OBJECTIVE: Spinal cord injuries generate the most negative response to medical
      treatment among all general body injuries. This important morbidity is thought to
      be caused by a complex secondary damage mechanism. In the present study, we
      examined the neuroprotective effects of alemtuzumab in a spinal cord trauma
      model. METHODS: We divided 24 Long-Evans male rats into 4 groups (n = 6 per
      group). Laminectomy was performed at T5-T8 in all groups. Trauma was applied
      using the Yasargil temporary aneurysm clip for 60 seconds at these spinal cord
      levels in all groups, except for group 1. Next, 1 mg/kg of alemtuzumab was
      administered to each rat in groups 3 and 4. A functional evaluation was performed
      on days 1, 3, and 5 in groups 1, 2, and 4, and the rats were then sacrificed. The
      rats in group 3 were sacrificed on the third postoperative day to observe the
      early effects of alemtuzumab. The biochemical examination findings of
      malondialdehyde and glutathione in plasma and tissue samples and
      histopathological findings of the spinal cord were evaluated and compared by
      statistical analysis. RESULTS: The inflammatory findings in the trauma group were
      not seen in either group treated with alemtuzumab. The clinical motor examination
      and inclined plane test results were also significantly better in these groups.
      CONCLUSION: Our results have shown that alemtuzumab might prevent spinal cord
      injury after trauma and is a histopathologically and biochemically strong anti
      inflammatory, antioxidant, and neuroprotective agent.

PMID- 30292668
TI  - The Application of FLOW 800 ICG Videoangiography Color Maps for Neurovascular
      Surgery and Intraoperative Decision Making.
AB  - BACKGROUND: Indocyanine green (ICG) videoangiography can assess cerebral blood
      flow, but results are primarily qualitative. FLOW 800 software measures
      fluorescence dynamics and creates a semiquantitative color delay map for
      assessment of relative sequence of blood flow within the vasculature. METHODS: We
      retrospectively reviewed 23 consecutive patients for whom FLOW 800 ICG
      videoangiography was used. They harbored aneurysms, arteriovenous malformations
      (AVMs), dural arteriovenous fistula (dAVF), or hemangioblastoma. Patients'
      characteristics, FLOW 800 data, and clinical findings were recorded. Color map
      data were readily available intraoperatively and guided surgery. RESULTS: The
      cohort included 10 patients with AVMs, 11 with aneurysms, 1 with dAVF, and 1 with
      hemangioblastoma. Approximately two thirds of patients underwent intraoperative
      angiography. FLOW 800 data provided semiquantitative data regarding localization,
      flow status in major feeding arteries, and dominance of the arterialized draining
      veins for AVMs, more than data from ICG videoangiography alone. For complex
      aneurysms, color maps confirmed relative adequate flow in parent and branching
      vessels. For the foramen magnum dAVF, the location of the dominant transdural
      connection was appreciated only via flow analysis. Flow analysis created the
      blood flow map of a large complex solid brainstem hemangioblastoma and guided
      devascularization. All FLOW 800 findings agreed with intraoperative and
      postoperative angiography. CONCLUSIONS: ICG videoangiography with FLOW 800
      analysis can provide semiquantitative and relative flow magnitude data that are
      efficient and noninvasive. This process helps identify early arterialized veins
      and their flow status during AVM and dAVF surgery and can confirm adequate
      relative flow within branching vessels during aneurysm surgery when clip-induced
      stenosis is suspected.

PMID- 30292669
TI  - Regional Variation in Opioid Use After Lumbar Spine Surgery.

PMID- 30292670
TI  - Enhanced exopolysaccharide production by Cordyceps militaris using repeated batch
      cultivation.
AB  - Cordyceps militaris exo-polysaccharides (EPS) have been reported to possess many
      benefits, such as anti-tumor, anti-inflammatory and antioxidant activities. In
      this study, the production of EPS via cultivation in a bioreactor was
      investigated. Glucose and yeast extract were determined to be the most suitable
      carbon and nitrogen sources for EPS production. The appropriate levels of glucose
      and yeast extract were 40 g/L and 10 g/L, respectively, resulting in EPS
      production of 1.686 g/L in a submerged culture. In the stirred-tank fermentor, an
      agitation rate of 150 rpm and aeration rate of 1.5 vvm were the most effective
      for EPS production. Due to the anchoring of mycelial cells on the wall of
      fermentor, a repeated batch approach was used. EPS production of C. militaris
      could be enhanced to a maximum of 5.713 g/L, with a productivity of 476 mg/L/day
      in the second run. The repeated batch approach was expected to generate higher
      EPS production, increase EPS yield and productivity and further simplify
      cultivation operations for bio-industrial application.

PMID- 30292671
TI  - Optimization of the treatment conditions with glycogen synthase kinase-3
      inhibitor towards enhancing the proliferation of human induced pluripotent stem
      cells while maintaining an undifferentiated state under feeder-free conditions.
AB  - The small molecule inhibitor CHIR99021 (CHIR) is well known as a selective
      glycogen synthase kinase-3 inhibitor. The purpose of our study was to optimize
      the conditions of CHIR supplementation that will enhance the proliferation of
      human induced pluripotent stem cells (hiPSCs) while maintaining their
      undifferentiated state under feeder-free conditions in adherent cultures for 4
      days. Our results revealed that both of the timing and concentration of CHIR
      affected cell behaviors of hiPSCs, such as colony formation, cell proliferation,
      and differentiation. The addition of 1-3 MUM CHIR to hiPSCs cultures in the late
      2-day period of a 4-day cultivation was effective in enhancing cell
      proliferation. Treatment with 3 MUM CHIR significantly enhanced cell
      proliferation, but led to differentiation of hiPSCs when the treatment was
      carried out over 4 days. Treatment with higher concentration of CHIR was also
      conducive to deviating hiPSCs from their undifferentiated state. Treatment with
      10 MUM CHIR led to decreased expression of pluripotency-associated genes and
      increased level of mesoderm marker genes, but failed to provided any growth
      promoting effect. Interestingly, when treatment with 1 MUM CHIR was confined to
      the late 2-day period of a 4-day cultivation, cell proliferation was enhanced
      without detectable deviation from the undifferentiated state as evidenced by the
      expression levels of pluripotency-associated genes, e.g., OCT3/4, NANOG, SOX2,
      and REX1. Repeated use of 1 MUM CHIR in subcultures provided no adverse effect on
      the proliferation of hiPSCs. Our results indicated that carefully designed CHIR
      treatment allows for enhanced proliferation of hiPSCs.

PMID- 30292672
TI  - The use of a standardized Chinese herbal formula in patients with advanced lung
      cancer: a feasibility study.
AB  - OBJECTIVE: Increasing numbers of cancer patients are using Chinese herbs (CHs).
      However, differences among prior studies make it difficult to draw firm
      conclusions about the clinical usefulness of any specific CH formula. The primary
      objective of this study was to establish the acceptability of taking a
      standardized CH formula for patients with advanced lung cancer. The secondary
      objective was to identify any toxicities attributable to this CH formula and to
      measure changes in quality of life. METHODS: A single-arm, prospective study of a
      6-week intervention with a selected CH formula in 15 patients with stage 4
      nonsmall-cell lung cancer (NSCLC, Seventh American Joint Committee on Cancer TNM
      staging system). RESULTS: Patients with advanced lung cancer were interested in
      using the CH formula. Completion (93%) and adherence (98%) levels were very high
      and most patients perceived the CH treatment as easy to take and were willing to
      take the CHs used in the study again if it was available. About half of the
      patients reported adverse events, all of which were mild (Grade 1 or 2) and only
      a small minority (8%) were potentially related to CHs. No biochemical or
      hematological evidence of toxicity was observed. Overall, there were improvement
      in quality of life, and reduced feelings of tiredness and sleepiness. CONCLUSION:
      This study provides preliminary evidence that short-term use of a carefully
      selected and prepared CH formula in patients with stage 4 NSCLC is acceptable and
      safe.

PMID- 30292673
TI  - A mechanistic model for thiol redox dynamics in the organogenesis stage rat
      conceptus.
AB  - Precise control of the glutathione/glutathione disulfide (GSH/GSSG) redox balance
      is vital for the developing embryo, but regulatory mechanisms are poorly
      understood. We developed a novel, mechanistic mass-balance model for GSH
      metabolism in the organogenesis stage (gestational day 10.0-11.13) rat conceptus
      predicting the dynamics of 8 unique metabolites in 3 conceptal compartments: the
      visceral yolk sac (VYS), the extra-embryonic fluid (EEF) and the embryo proper
      (EMB). Our results show that thiol concentrations in all compartments are well
      predicted by the model. Protein synthesis is predicted to be a major efflux
      pathway for all amino acid precursors of GSH synthesis and an essential model
      element. Our model provides quantitative insights in the transport fluxes and
      enzymatic fluxes needed to maintain thiol redox balances under normal
      physiological conditions. This is crucial to further elucidate the mechanisms
      through which chemical exposure can perturb redox homeostasis, causing oxidative
      stress, and potentially birth defects.

PMID- 30292674
TI  - Erythropoietin-producing hepatocellular A7 triggering ovulation indicates a
      potential beneficial role for polycystic ovary syndrome.
AB  - BACKGROUND: The ovulatory dysfunction mechanisms underlying polycystic ovary
      syndrome (PCOS) are not completely understood. And the roles of EPHA7 and EPHA7
      regulated pathway factors in the pathogenesis of anovulation remain to be
      elucidated. METHODS: We used human granulosa cells (hGCs) of PCOS and non-PCOS
      patients to measure EPHA7 and other target gene expressions. We performed in
      vitro experiments in KGN cells to verify the molecular mechanisms. Additionally,
      we conducted in vivo loss- and gain-of-function studies using EPHA7 shRNA
      lentivirus and recombinant EPHA7-Fc protein injection to identify the ovulation
      effects of EPHA7. FINDINGS: EPHA7 functions as a critically positive upstream
      factor for the expression of ERK1/2-mediated C/EBPbeta. This protein, in turn,
      induced the expression of KLF4 and then ADAMTS1. Moreover, decreased abundance of
      EPHA7 was positively correlated with that of its downstream factors in hGCs of
      PCOS patients. Additionally, a 1-week functional EPHA7 shRNA lentivirus in rat
      ovaries contributed to decreased numbers of retrieved oocytes, and a 3-week
      functional lentivirus led to menstrual disorders and morphological polycystic
      changes in rat ovaries. More importantly, we found that EPHA7 triggered ovulation
      in rats, and it improved polycystic ovarian changes induced by DHEA in PCOS rats.
      INTERPRETATION: Our findings demonstrate a new role of EPHA7 in PCOS, suggesting
      that EPHA7 is an effective target for the development of innovative medicines to
      induce ovulation. FUND: National Key Research and Development Program of China,
      National Natural Science Foundation, Shanghai Municipal Education Commission-
      Gaofeng Clinical Medicine, and Shanghai Commission of Science and Technology.

PMID- 30292676
TI  - Determination of the microbiological contamination in minced pork by culture
      dependent and 16S amplicon sequencing analysis.
AB  - Routine evaluation of bacterial contamination in minced pork is still mainly
      performed by the enumeration of indicator bacteria, including total aerobic
      colony count and E. coli, using standardized isolation methods. However, the
      bacterial community structure as well as the effect of the storage time and
      temperature on the aerobic plate count are largely unknown for this matrix. The
      aim of the study was to characterize the microbial community in minced pork by
      16S rRNA amplicon sequencing compared to classical isolation methods combined
      with identification by Matrix-assisted laser desorption ionization-time of flight
      mass spectrometry (MALDI TOF MS) and 16S rRNA gene sequencing. Analysis of 14
      unrelated samples showed that total aerobic counts determined at 30  degrees C
      and 7  degrees C showed no significant difference, but the richness was higher on
      PCA at 30  degrees C for 7 samples, equal in 5, and higher at 7  degrees C for 2
      samples. Members of the genus Pseudomonas, along with the genera Brochothrix and
      Carnobacterium were commonly identified among both the mesophilic and
      psychrotrophic population. Comparing to 16S rRNA amplicon sequencing, some
      contrasting data were obtained. Except for Brochothrix spp. and Pseudomonas spp.,
      that were abundant and always detected, genera obtained with the two methods in
      the same sample were not always the same. Comparison of different sample
      preparation techniques and DNA extraction methods demonstrated also in this
      matrix that different results on the microbial composition and complexity are
      obtained. Present data illustrate that the combined isolation and identification
      of isolates using MALDI TOF MS and 16S gene sequencing and overall community
      profiling using 16S rRNA amplicon sequencing provides complementary results and
      yields important insights into the complex relationship between microorganisms in
      a food.

PMID- 30292677
TI  - Predicting heat process efficiency in thermal processes when bacterial
      inactivation is not log-linear.
AB  - The food industry widely uses the F-value which considers microbial log-linear
      inactivation, while microbial heat inactivation may result in a non-log-linear
      inactivation pattern due to genetic or phenotypical heterogeneity. This may yield
      discrepancies in predicting microbial heat inactivation under dynamic conditions
      of heat treatment. In this paper, we suggest the calculation of the equivalent
      time of heat treatment at a given temperature to overcome these constraints. To
      validate our proposal, the heat inactivation of Bacillus pumilus, showing non-log
      linear behavior, was predicted for 4 different heat inactivation profiles and
      bacterial enumeration was performed to determine whether prediction errors were
      acceptable. When the proportion of residuals in an acceptable zone from 1 log
      (fail safe) to 0.5 log (fail dangerous) was greater or equal to 70%, the model
      was considered as acceptable for predictions of the tested data. The new approach
      gave four different temperature profiles, with 96, 85, 85 and 100% of the
      residuals in the acceptable zone, indicating satisfactory prediction. Thus the
      proposed practical alternative to simulate microbial heat inactivation kinetics
      is able to extend the F-value to non-log-linear inactivation patterns.

PMID- 30292678
TI  - Development and optimization of antifungal packaging for sliced pan loaf based on
      garlic as active agent and bread aroma as aroma corrector.
AB  - The aim of the present work was the development of antimicrobial films containing
      garlic extract to be applied as active packaging for preservative-free sliced pan
      loaf, with the goal of extending its shelf-life. First, the antimicrobial
      capacity of garlic extract, a compound used as active agent, was tested against
      Penicillium expansum by the disc diffusion method. The extract showed high
      antimicrobial activity, 0.1 MUL per Petri dish being the minimum inhibitory
      amount, and 0.25 MUL the minimum fungicidal amount. Bread aroma was also used to
      mask the pungent odour of garlic and it was confirmed to have no antimicrobial
      activity. Subsequently, polyethylene (PE) aqueous emulsion and ethylene-vinyl
      alcohol copolymer (EVOH) and zein hydroalcoholic solutions containing 0.25 and
      0.5% (w/w per dry polymer) of garlic extract and bread aroma were used to coat PE
      films, producing PE/PE, PE/EVOH and PE/zein active films. The antimicrobial
      capacity of the films was studied in vitro against Penicillium expansum, and in
      vivo with natural sliced bread. The results showed that all the films presented
      some antimicrobial activity, PE film coated with zein containing 0.5% of garlic
      extract and bread aroma being the film presenting the best results, maintaining
      bread free of mould infection for 30 days. Sensory tests showed that the addition
      of 1% of bread aroma improved the sensory experience of consumers and also
      revealed good purchase intention.

PMID- 30292675
TI  - Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in
      multiple sclerosis.
AB  - BACKGROUND: Adapted ketogenic diet (AKD) and caloric restriction (CR) have been
      suggested as alternative therapeutic strategies for inflammatory,
      hyperproliferative and neurodegenerative diseases. Pro-inflammatory eicosanoids
      have been implicated in the pathogenesis of multiple sclerosis since they augment
      vascular permeability and induce leukocyte migration into the brain. We explored
      the impact of ketogenic diets on gene expression of biosynthetic enzymes for pro-
      (ALOX5, COX1, COX2) and anti-inflammatory (ALOX15) eicosanoids in patients with
      relapsing-remitting multiple sclerosis. METHODS: 60 adults were prospectively
      recruited for this six months randomized controlled trial and the impact of
      dietary treatment on the Multiple Sclerosis Quality of Life-54 index
      (ClinicalTrials.gov (NCT01538355) has previously been published. Here we explored
      24 patients (8 controls, 5 on CR and 11 on AKD). For statistical analysis we
      combined the two diet groups to a single pooled treatment group. FINDINGS: Inter
      group comparison indicated that expression of the pro-inflammatory ALOX5 in the
      pooled treatment group was significantly (p < 0.05) reduced when compared with
      the control group. Moreover, intra-group comparison (same individuals before and
      after dietary treatment) suggested significantly impaired expression of other pro
      inflammatory enzymes, such as COX1 (p < 0.001) and COX2 (p < 0.05). Finally,
      pretreatment cross-group analysis revealed a significant positive correlation
      between expression of pro-inflammatory ALOX5 and COX2 and an inverse correlation
      of ALOX5 and COX1 expression with the MSQoL-54 index. INTERPRETATION: Ketogenic
      diets can reduce the expression of enzymes involved in the biosynthesis of pro
      inflammatory eicosanoids. Pharmacological interference with eicosanoid
      biosynthesis might constitute a strategy supplementing current therapeutic
      approaches for MS.

PMID- 30292679
TI  - Micro patterning of hydroxyapatite by soft lithography on hydrogels for selective
      osteoconduction.
AB  - Mechanically robust hydrogels are promising biomaterials as artificial supportive
      tissue. These applications require selective and robust bonding of the hydrogels
      to living tissue. Recently, we achieved strong in vivo bone bonding of a tough
      double network (DN) hydrogel, a potential material for use as artificial
      cartilage and tendon, by hybridizing osteoconductive hydroxyapatite (HAp) in the
      gel surface layer. In this work, we report micro patterning of HAp at the surface
      of the DN hydrogel for selective osteoconduction. Utilizing the dissolution of
      HAp in an acidic environment, the soft lithography technique using an acid gel
      stamp was adopted to form a high-resolution HAp pattern on the gel. The HAp
      patterned gel showed well-regulated migration and adhesion of cells in vitro.
      Moreover, the HAp-patterned gel showed selective and robust bonding to the rabbit
      bone tissue in vivo. This HAp soft lithography technique allows for simple and
      quick preparation of tailor-made osteoconductive hydrogels and can be applied to
      other hydrogels for selective bone bonding. STATEMENT OF SIGNIFICANCE: Hydrogels,
      preserving large amount of water, have been studied for next-generation
      artificial soft tissues. However, fixation of hydrogels to living tissue was
      unsolved issue for clinical application. Recently, we achieved robust bonding of
      a tough double network gel to bone in vivo by coating of osteoconductive
      hydroxyapatite in the gel surface layer. For further progress for practical use,
      we report the micro patterning of HAp at the surface of the DN hydrogel by using
      soft lithography technique, to perform selective bonding to only objective area
      without unnecessary coalescence. The HAp lithography technique is simple, quick
      and non-toxic method to prepare tailor-made osteoconductive hydrogels and has
      universality of species of hydrogels.

PMID- 30292680
TI  - Significance of preoperative acute kidney injury in patients with acute type A
      aortic dissection.
AB  - BACKGROUND/PURPOSE: Acute type A aortic dissection (AAD) is a medical emergency
      with high mortality even with emergency repair. We explored the risk factors for
      in-hospital mortality and the impact of preoperative acute kidney injury (AKI) in
      patients with AAD. METHODS: Our hospital database contained records for 156
      consecutive patients who underwent AAD repair between March 2000 and February
      2013. They were assigned to the in-hospital mortality or the survival group. All
      data were collected retrospectively. RESULTS: The 30-day mortality, including
      intraoperative deaths, was 14.1% (22/156). Total in-hospital mortality was 19.2%
      (30/156). Patients who required preoperative cardiopulmonary resuscitation (CPR)
      (16.7 vs 3.2%; P = 0.012), or who presented with preoperative cardiac tamponade
      (46.7 vs 19.0%; P = 0.002), shock/hypotension (56.7 vs 21.4%; P < 0.001), or coma
      (20.0 vs 6.3%; P = 0.019) had a higher in-hospital mortality rate. There was no
      difference in in-hospital mortality rate between patients with preoperative AKI
      or not. Mortality and major complications were significantly correlated with the
      severity of AKI. Multivariate analysis confirmed that preoperative shock or
      hypotension (odds ratio = 5.2; 95% CI = 2.2-12.3), and preoperative AKI stage 3
      (odds ratio = 4.9; 95% CI = 1.3-19.3) were independent preoperative prognostic
      factors of in-hospital mortality. CONCLUSION: On the basis of our results,
      preoperative stage 3 AKI is a crucial prognostic risk factor for patients with
      AAD repair, Cardiac surgeons should be aware of this condition when dealing with
      AAD patients.

PMID- 30292681
TI  - Skewed ratio between type 1 and type 2 calreticulin mutations in essential
      thrombocytosis patients with concomitant Janus kinase 2 V617F mutation.
AB  - Detection of somatic mutations in cardinal driver genes is a strong argument for
      diagnosis in classical Philadelphia-negative myeloproliferative neoplasms (MPNs).
      Driver mutations in Janus kinase 2 (JAK2), calreticulin (CALR), and XXXX (MPL),
      are generally considered mutually exclusive, but several reports have suggested
      that they coexist in a small subgroup of patients. In this study, we
      retrospectively searched for CALR mutations in 136 suspected MPN patients with
      low allelic burden (<=5%) JAK2 V617F. Fifteen patients with concomitant JAK2
      V617F and CALR mutations were identified, of whom 10 were diagnosed with
      essential thrombocytosis (ET). More than 50 different indel mutations in exon 9
      of CALR have been reported, with type 1 (52 bp deletion) and type 2 (5 bp
      insertion) accounting for more than 80% of CALR-mutated MPN cases. Type 1 is
      generally considered the most common mutation, but, interestingly, our double
      mutated ET patients seem to have an inversed ratio between type 1 and type 2 CALR
      mutations. Our findings support the possibility of coexisting JAK2 V617F and CALR
      mutations and stress the importance of further molecular screening in MPN
      patients with low allele frequencies of JAK2 V617F.

PMID- 30292682
TI  - 2-Cys Peroxiredoxins Participate in the Oxidation of Chloroplast Enzymes in the
      Dark.
AB  - Most redox-regulated chloroplast enzymes are reduced during the day and oxidized
      during the night. While the reduction mechanism of light-dependent enzymes is
      well known, the mechanism mediating their oxidation in the dark remains unknown.
      The thiol-dependent peroxidases, 2-Cys peroxiredoxins (Prxs), play a key role in
      light-dependent reduction of chloroplast enzymes. Prxs transfer reducing
      equivalents of thiols to hydrogen peroxide, suggesting the participation of these
      peroxidases in enzyme oxidation in the dark. Here, we have addressed this issue
      by analyzing the redox state of well-known redox-regulated chloroplast enzymes in
      response to darkness in Arabidopsis thaliana mutants deficient in chloroplast
      localized Prxs (2-Cys Prxs A and B, Prx IIE, and Prx Q). Mutant plants lacking 2
      Cys Prxs A and B, and plants overexpressing NADPH-dependent thioredoxin (Trx)
      reductase C showed delayed oxidation of chloroplast enzymes in the dark. In
      contrast, the deficiencies of Prx IIE or Prx Q exerted no effect. In vitro assays
      allowed the reconstitution of the pathway of reducing equivalents from reduced
      fructose 1,6-bisphosphatase to hydrogen peroxide mediated by Trxs and 2-Cys Prxs.
      Taken together, these results suggest that 2-Cys Prxs participate in the short
      term oxidation of chloroplast enzymes in the dark.

PMID- 30292683
TI  - Medicago AP2-Domain Transcription Factor WRI5a Is a Master Regulator of Lipid
      Biosynthesis and Transfer during Mycorrhizal Symbiosis.
AB  - Most land plants have evolved a mutualistic symbiosis with arbuscular mycorrhiza
      (AM) fungi that improve nutrient acquisition from the soil. In return, up to 20%
      of host plant photosynthate is transferred to the mycorrhizal fungus in the form
      of lipids and sugar. Nutrient exchange must be regulated by both partners in
      order to maintain a reliable symbiotic relationship. However, the mechanisms
      underlying the regulation of lipid transfer from the plant to the AM fungus
      remain elusive. Here, we show that the Medicago truncatula AP2/EREBP
      transcription factor WRI5a, and likely its two homologs WRI5b/Erf1 and WRI5c, are
      master regulators of AM symbiosis controlling lipid transfer and periarbuscular
      membrane formation. We found that WRI5a binds AW-box cis-regulatory elements in
      the promoters of M. truncatula STR, which encodes a periarbuscular membrane
      localized ABC transporter required for lipid transfer from the plant to the AM
      fungus, and MtPT4, which encodes a phosphate transporter required for phosphate
      transfer from the AM fungus to the plant. The hairy roots of the M. truncatula
      wri5a mutant and RNAi composite plants displayed impaired arbuscule formation,
      whereas overexpression of WRI5a resulted in enhanced expression of STR and MtPT4,
      suggesting that WRI5a regulates bidirectional symbiotic nutrient exchange.
      Moreover, we found that WRI5a and RAM1 (Required for Arbuscular Mycorrhization
      symbiosis 1), which encodes a GRAS-domain transcription factor, regulate each
      other at the transcriptional level, forming a positive feedback loop for
      regulating AM symbiosis. Collectively, our data suggest a role for WRI5a in
      controlling bidirectional nutrient exchange and periarbuscular membrane formation
      via the regulation of genes involved in the biosynthesis of fatty acids and
      phosphate uptake in arbuscule-containing cells.

PMID- 30292684
TI  - New insights into the pathophysiology of fasciculations in amyotrophic lateral
      sclerosis: An ultrasound study.
AB  - OBJECTIVE: To describe the fasciculation pattern in ALS and to analyse its
      clinical and pathophysiological significance. METHODS: Ultrasound of 19 muscles
      was performed in 44 patients with a recent diagnosis (<90 days) of ALS. The
      number of fasciculations was recorded in each muscle and the muscle thickness and
      strength were additionally measured in limb muscles. A subgroup of patients were
      electromyographically assessed. RESULTS: US was performed in 835 muscles and EMG
      was available in 263 muscles. US detected fasciculations more frequently than
      EMG. Fasciculations were widespread, especially in upper limbs onset patients and
      in the cervical region. Fasciculations' number inversely associated with ALSFR-R
      and body mass index (BMI) and directly with BMI loss and upper motor neuron (UMN)
      impairment. Our statistical model suggest that fasciculations increase with the
      initial lower motor neuron (LMN) degeneration, reach their peak when the muscle
      became mildly to moderately weak, decreasing afterwards with increasing muscle
      weakness and atrophy. CONCLUSIONS: Our study suggests that both UMN and LMN
      degeneration trigger fasciculations causing BMI loss. The degree of LMN
      impairment could account for differences in fasciculations' rates within and
      between muscles. SIGNIFICANCE: In ALS, fasciculations could explain the link
      between hyperexcitability and BMI loss.

PMID- 30292685
TI  - Criteria wanted. Is the brain dead or alive?

PMID- 30292686
TI  - Corrigendum to "Allantoin contributes to the stress response in cadmium-treated
      Arabidopsis roots" [Plant Physiol. Biochem. 119 (October 2017) 103-109].

PMID- 30292687
TI  - The increased severity of acute pancreatitis in the elderly is mainly related to
      intestinal barrier dysfunction.

PMID- 30292688
TI  - Nickel spiking to improve the methane yield of sewage sludge.
AB  - The presence of micro-nutrients can be stimulatory for the anaerobic digestion
      (AD) of hardly degradable wastes and thus, improve process performance. Among the
      essential trace elements, nickel is involved in multiple important enzymes
      necessary for efficient AD. The present study investigates the effect of nickel
      spiked sewage sludge on batch and continuous mode operation. Metal spiking was
      conducted in the form of nanoparticles (Ni-NPs) and salt (NiCl2.6H2O). Results
      from batch assays showed that 5 mgNi-Salt/kgVS in the presence of
      Nitrilotriacetic acid (NTA) enhanced the methane yield by ~10% compared to the
      untreated sample. The impact of Ni-NPs in the AD process was also positive, but
      slightly lower compared to the effect of NiCl2.6H2O. The stimulatory impact of Ni
      was also revealed in continuously fed digester boosting the methane yield by ~8%.
      Overall, the improved methane production indicated that methanogenic archaea were
      favoured by the simultaneous supplementation of Ni and NTA.

PMID- 30292689
TI  - Bidirectional extracellular electron transfers of electrode-biofilm: Mechanism
      and application.
AB  - The extracellular electron transfer (EET) between microorganisms and electrodes
      forms the basis for microbial electrochemical technology (MET), which recently
      have advanced as a flexible platform for applications in energy and environmental
      science. This review, for the first time, focuses on the electrode-biofilm
      capable of bidirectional EET, where the electrochemically active bacteria (EAB)
      can conduct both the outward EET (from EAB to electrodes) and the inward EET
      (from electrodes to EAB). Only few microorganisms are tested in pure culture with
      the capability of bidirectional EET, however, the mixed culture based
      bidirectional EET offers great prospects for biocathode enrichment, pollutant
      complete mineralization, biotemplated material development, pH stabilization, and
      bioelectronic device design. Future efforts are necessary to identify more EAB
      capable of the bidirectional EET, to balance the current density, to evaluate the
      effectiveness of polarity reversal for biocathode enrichment, and to boost the
      future research endeavors of such a novel function.

PMID- 30292690
TI  - Replicative aging as a source of cell heterogeneity in budding yeast.
AB  - While deviations from the optimal phenotype are deleterious, increased variation
      can prevent population extinction under severe stresses. Cell division asymmetry
      is an important source of microbial phenotypic heterogeneity. A consecutive set
      of asymmetric divisions can cause the gradual accumulation of deleterious factors
      and, at late stages, the death of old pole (mother) cells. This phenomenon is
      known as replicative aging. As the old cells are constantly being diluted by the
      progeny, the majority of a microbial population is represented by replicatively
      young cells. Therefore, early-age changes in yeast mother cells have a much
      greater impact on the integral performance of the microbial population than does
      functional deterioration at later ages. Here, we review the early manifestations
      of replicative aging in Saccharomyces cerevisiae mother cells that occur during
      the first ten cell cycles. Early age-dependent changes occur in stress
      resistance, genomic instability, protein aggregate levels, redox balance and
      metabolism. We speculate that some of these manifestations can be beneficial
      during stress exposure; therefore, early aging may be a bet-hedging mechanism.
      Together, the data suggest that the age component of variation in populations of
      asymmetrically dividing microorganisms is substantial and may play an important
      role in adaptations to changing environments.

PMID- 30292691
TI  - Toxicity of lupane derivatives on anionic membrane models, isolated rat
      mitochondria and selected human cell lines: Role of terminal alkyl chains.
AB  - Triterpenoids have multiple biological properties, although little information is
      available regarding their toxicity. The present study evaluates the toxicity of
      two new synthetic lupane derivatives using distinct biological models including
      synthetic lipids membranes, isolated liver and heart mitochondria fractions, and
      cell lines in culture. The two novel triterpenoids caused perturbations in the
      organization of synthetic lipid bilayers, leading to changes in membrane
      fluidity. Inhibition of cell proliferation and mitochondrial and nuclear
      morphological alterations were also identified. Inhibition of mitochondrial
      oxygen consumption, transmembrane electric potential depolarization and induction
      of the mitochondrial permeability transition pore was observed, although effects
      on isolated mitochondrial fractions were tissue-dependent (e.g. liver vs. heart).
      The size and length of hydrocarbon chains in the two molecules appear to be
      determinant for the degree of interaction with mitochondria, especially in the
      whole cell environment, where more barriers for diffusion exist. The results
      suggest that the positively charged triterpenoids target mitochondria and disrupt
      bioenergetics.

PMID- 30292692
TI  - Reliability of microvascular responsiveness measures derived from near-infrared
      spectroscopy across a variety of ischemic periods in young and older individuals.
AB  - BACKGROUND: Cardiovascular disease (CVD) is associated with impairments in
      microvascular responsiveness. Therefore, reliably assessing microvascular
      function is clinically relevant. Thus, this study aimed to examine the
      reliability of the near-infrared spectroscopy (NIRS)-derived oxygen saturation
      (StO2) reperfusion slope, a measure of microvascular responsiveness, to four
      different vascular occlusion tests (VOT) of different durations in young and
      older participants. METHODS: Eight healthy young (29 +/- 5 yr) and seven older
      (67 +/- 4 yr) men participated in four NIRS combined with VOT (NIRS-VOT; 30 s, 1,
      3, and 5 min) in the leg microvasculature on two visits separated by 1-2 weeks.
      Vascular responsiveness was determined by the StO2 reperfusion slope. The
      coefficient of variation (CV), repeatability, reliability (ICC), and the limits
      of agreement (LOA) were calculated for the NIRS-derived reperfusion slopes for
      each occlusion duration and visit. RESULTS: CV for the StO2 reperfusion slope
      following 30 s, 1, 3 and 5 min of occlusion were 33 +/- 29%, 19 +/- 21%, 14 +/-
      12%, and 12 +/- 10%, respectively. Repeatability values following 30 s, 1, 3 and
      5 min occlusions were 20%, 1%, 4% and 21%, respectively. The ICC for the StO2
      reperfusion slopes for each occlusion duration were 0.29, 0.42, 0.84, and 0.88
      following 30 s, 1, 3 and 5 min of occlusion, respectively. LOA values between
      visit 1 and 2 for occlusions were not different from zero. There were no age
      related differences for all variables of the study. CONCLUSION: NIRS-derived StO2
      reperfusion slope, has good reliability across a range of occlusion durations
      with the strongest reliability during longer occlusion durations.

PMID- 30292693
TI  - Ragweeds and relatives: Molecular phylogenetics of Ambrosiinae (Asteraceae).
AB  - Ambrosiinae are one of the most distinct subtribes in the Heliantheae alliance
      (Asteraceae), mainly due to specialization toward wind pollination. Taxa of the
      subtribe are principally native to the Americas, although some species have
      attained a cosmopolitan distribution. Members of subtribe Engelmanniinae are
      considered close to Ambrosiinae, due to shared morphological traits. However, the
      placement of Ambrosiinae within the Heliantheae alliance has not yet been
      corroborated by phylogenetic analyses. In the present study, we test the
      circumscription of subtribe Ambrosiinae and examine relationships among its
      genera. We used sequence information from three plastid (psbA-trnH, trnQ-rps16
      and trnL-F) and two nuclear (ITS and D35) marker regions. Phylogenetic inference
      analyses were conducted, applying Bayesian Inference (BI) and Maximum Likelihood
      (ML). Subtribe Ambrosiinae is found monophyletic or nearly so in all analyses.
      The genera Dugesia and Rojasianthe (previously considered part of subtribe
      Engelmanniinae) in some cases cluster together with Ambrosiinae; these genera are
      clearly not part of Engelmanniinae. Within Ambrosiinae, the genera Parthenium and
      Parthenice occupy basal positions, whereas members of the genus Ambrosia are the
      most derived representatives of the subtribe. Previous subdivision of Ambrosiinae
      into "Iveae" (members having androgynous capitula and free achenes) and
      "Ambrosieae" (genera with unisexual heads and achenes enclosed in burs) is not
      corroborated. Results also allow consideration of relationships among species and
      subgeneric groups within Parthenium, Iva, and Ambrosia.

PMID- 30292694
TI  - Phenotypic and life-history diversification in Amazonian frogs despite past
      introgressions.
AB  - The advent of genomics in phylogenetics and population genetics strengthened the
      perception that conflicts among gene trees are frequent and often due to
      introgression. However, hybridization occurs mostly among species that exhibit
      little phenotypic differentiation. A recent study delineating species in
      Anomaloglossus, a frog genus endemic to the Guiana Shield, identified an
      intriguing pattern in the A. baeobatrachus species complex. This complex occurs
      in French Guiana and Amapa (Brazil) and comprises two sympatric phenotypes
      contrasting not only in body size, habitat, and advertisement call, but also in
      larval development mode (endotrophic vs exotrophic tadpoles). However, molecular
      and phenotypic divergences are, in some cases, incongruent, i.e specimens sharing
      mtDNA haplotypes are phenotypically distinct, suggesting a complex evolutionary
      history. Therefore, we genotyped 106 Anomaloglossus individuals using ddRADseq to
      test whether this phenotype/genotype incongruence was a product of phenotypic
      plasticity, incomplete lineage sorting, multiple speciation events, or admixture.
      Based on more than 16,000 SNPs, phylogenetic and population genetic approaches
      demonstrated that exotrophic populations are paraphyletic. Species tree and
      admixture analyses revealed a strikingly reticulate pattern, suggesting multiple
      historical introgression events. The evolutionary history of one exotrophic
      population in northern French Guiana is particularly compelling given that it
      received genetic material from exotrophic ancestors but shows very strong genetic
      affinity with the nearby endotrophic populations. This suggests strong selection
      on larval development and mating call after secondary contact and hybridization.
      The case of A. baeobatrachus represents a striking example of introgression among
      lineages that are phenotypically distinct, even in their larval development mode,
      and highlights how high-resolution genomic data can unravel unexpectedly complex
      evolutionary scenarios.

PMID- 30292695
TI  - Corrigendum to " An extra priming dose of hepatitis A vaccine to adult patients
      with rheumatoid arthritis and drug induced immunosuppression - A prospective,
      open-label, multi-center study" [Trav. Med. Infect. Dis. 21, January-February
      2018, 43-50].

PMID- 30292697
TI  - The dynamic-lymphaticovenular anastomosis method for breast cancer treatment
      related lymphedema: Creation of functional lymphaticovenular anastomoses with use
      of preoperative dynamic ultrasonography.
AB  - BACKGROUND: Lymphaticovenular anastomosis (LVA) is generally an effective
      procedure for breast cancer treatment-related upper extremity lymphedema (UEL).
      Clinical improvement is, however, limited by the degree of sclerosis of the
      lymphatic vessels. We have developed a method by which we use dynamic
      ultrasonography to depict vessels through which lymph can be propelled into the
      LVA under the power of the patient's natural hand movements. METHODS: We assessed
      the dynamic-LVA method by comparing clinical details of 15 cases of breast cancer
      treatment-related lymphedema treated by dynamic LVA and 15 corresponding cases
      treated by conventional LVA. RESULTS: Placement of incisions at a total of 90
      forearm sites (three per patient) yielded 90 LVAs (32 in "linear ICG lymphography
      pattern incisions" and 58 in "stardust pattern incisions"). Sclerotic lymphatic
      vessels were encountered at greater frequency in "linear pattern incisions" in
      the dynamic LVA group than in the conventional LVA group (7.1% vs. 38.9%, P =
      0.030). Postoperative volume reduction was significantly greater in the dynamic
      LVA group than in the conventional LVA group; the UEL index at 1 month was 8.12
      +/- 3.08 vs. 3.74 +/- 5.82, respectively (P = 0.018), and at 1 year was 10.23 +/-
      6.16 vs. 2.03 +/- 9.36, respectively (P = 0.014). CONCLUSIONS: Dynamic LVA is
      clinically beneficial because the imaging guides decisions over the locations
      where the incisions should be placed so that a patient's natural hand motions can
      be used to propel lymph into the anastomosis despite the presence of sclerosis
      and because even early improvements are obtained.

PMID- 30292696
TI  - Variation in the perioperative care of women undergoing abdominal-based
      microvascular breast reconstruction in the United Kingdom (The optiFLAPP Study).
AB  - INTRODUCTION: Abdominal-based microvascular breast reconstruction constitutes
      approximately one-fifth of reconstructions following mastectomy for breast
      cancer. Enhanced recovery after surgery (ERAS) protocols have been implemented to
      improve patient care. The aim of this project was to identify variation in the
      perioperative care of women undergoing microvascular breast reconstruction to
      inform development of an ERAS protocol. METHODS: Surveys were developed for
      plastic surgeons, anaesthetists and the lead clinician for breast reconstruction
      at each unit. These assessed most aspects of perioperative care. A team of
      medical student collaborators was identified. This team created a list of
      surgeons and anaesthetists in the United Kingdom by unit. REDCap was used to
      record their responses. RESULTS: Nineteen (19/39, 49%) lead clinicians, 83
      (83/134, 62%) plastic surgeons and 71 (71/100, 71%) anaesthetists from units
      across the UK completed the surveys. Marked variation was identified in the
      clinician responses when compared with the national and international guidelines.
      This variation covered many aspects of patient care including antibiotic and
      fluid prescribing, surgical technique, post-operative care and recording of
      patient outcomes. CONCLUSIONS: The optiFLAPP national practice survey has
      demonstrated variation in the perioperative care of women undergoing abdominal
      based microvascular breast reconstruction. We propose a large prospective audit
      to assess current protocols and support development of randomised controlled
      trials.

PMID- 30292698
TI  - A CT-image based pig atlas model and its potential applications in the meat
      industry.
AB  - In this communication we present a novel pig atlas model which is represented by
      a parametric linear Lagrange or cubic Hermite mesh. The model is developed from
      data points digitized from a 3D pig CT image. In total 84 muscles and 121 bones
      are included in the atlas, representing the tissue structures most relevant to
      the industry. We discuss its potential applications in virtual meat cuts and
      statistical shape analysis for pig breeding and genetics companies.

PMID- 30292699
TI  - Influence of extending the pre-slaughter interval after second vaccination on the
      carcass cutting yield and the quality of meat from immunocastrated lambs.
AB  - The influence of extending the vaccination-to-slaughter interval of
      immunocastrated lambs on carcass cutting yield and meat quality of the
      Longissimus thoracis (LT) muscle was investigated in forty Dohne Merino lambs
      (8.5 months old; 53.7 +/- 4.8 kg). Immunocastration booster vaccination intervals
      of six (IC6; n = 10) and four (IC4; n = 10) weeks prior to the slaughter age were
      used, with two weeks between primary and secondary vaccinations. A further 10
      lambs were Burdizzo-castrated at 6.5 months old (B). The control treatment
      remained intact (R; n = 10). Prime cutting yields, LT muscle area, LT
      subcutaneous fat thickness and instrumental meat quality were accessed. Both
      castration methods increased LT fat thickness and decreased meat CIE a* (redness)
      values. Extending the vaccination-to-slaughter interval of immunocastrates
      increased the gastrointestinal tract fat and decreased meat redness.
      Immunocastration of male lambs can thus be used to manipulate backfat without
      negatively influencing carcass weight, cutting yield or meat quality.

PMID- 30292700
TI  - Special-Fed Veal: Separable components, proximate composition, and nutrient
      analysis of selected raw and cooked, wholesale and retail cuts.
AB  - Nutrition research continues to be important for consumers to make informed food
      purchasing decisions and is used in nutrition policy decisions. The objective of
      this study was to analyze the nutrient concentration of raw and cooked cuts from
      special-fed veal calves to update nutrient data in the USDA National Nutrient
      Database for Standard Reference (SR) Release 27. Packages of wholesale (whole
      loin roasts, center-cut hindshanks and ground veal) and retail veal cuts (osso
      buco foreshanks, loin chops, leg cutlets and shoulder blade chops) were randomly
      collected in original vacuum packaging from six U.S. suppliers. Packages were
      shipped to the Colorado State University Meat Laboratory for cut dissection,
      cooking, and nutrient analysis. Composites of lean, external fat and seam fat
      were formed for analysis of proximate, fatty acid, vitamin and mineral
      composition. Results from this study identified additional fatty acids,
      established choline concentration, and provided updated veal nutrient composition
      information for inclusion in USDA SR 27.

PMID- 30292701
TI  - Comparison of a computer vision system vs. traditional colorimeter for color
      evaluation of meat products with various physical properties.

PMID- 30292702
TI  - The external genitalia in juvenile Caiman latirostris differ in hormone sex
      determinate-female from temperature sex determinate-female.
AB  - The broad-snouted caiman (Caiman latirostris) is a crocodilian species that
      inhabits South American wetlands. As in all other crocodilians, the egg
      incubation temperature during a critical thermo-sensitive window (TSW) determines
      the sex of the hatchlings, a phenomenon known as temperature-dependent sex
      determination (TSD). In C. latirostris, we have shown that administration of 17
      beta-estradiol (E2) during the TSW overrides the effect of the male-producing
      temperature, producing phenotypic females (E2SD-females). Moreover, the
      administration of E2 during TSW has been proposed as an alternative way to
      improve the recovery of endangered reptile species, by skewing the population sex
      ratio to one that favors females. However, the ovaries of E2SD-female caimans
      differ from those of TSD-females. In crocodilians, the external genitalia (i.e.
      clitero-penis structure or phallus) are sexually dimorphic and hormone-sensitive.
      Despite some morphological descriptions aimed to facilitate sexing, we found no
      available data on the C. latirostris phallus histoarchitecture or hormone
      dependence. Thus, the aims of this study were: (1) to establish the temporal
      growth pattern of the phallus in male and female caimans; (2) to evaluate histo
      morphological features and the expression of estrogen receptor alpha (ERalpha)
      and androgen receptor (AR) in the phallus of male and female pre-pubertal
      juvenile caimans; and (3) to determine whether the phallus of TSD-females differs
      from the phallus of E2SD-females. Our results demonstrated sexually dimorphic
      differences in the size and growth dynamics of the caiman external genitalia,
      similarities in the shape and spatial distribution of general histo-morphological
      compartments, and sexually dimorphic differences in innervation, smooth muscle
      fiber distribution, collagen organization, and ERalpha and AR expressions. The
      external genitalia of E2SD-females differed from that of TSD-females in many
      histological features and in the expression of ERalpha and AR, resembling
      patterns described in males. Our results alert on the effects of estrogen agonist
      exposure during TSW and suggest that caution must be taken regarding the use of
      E2SD as a procedure for wildlife population management.

PMID- 30292703
TI  - Diversity of aminoglycoside modifying enzymes and 16S rRNA methylases in
      Acinetobacter baumannii and Acinetobacter nosocomialis species in Iran; wide
      distribution of aadA1 and armA.
AB  - PURPOSE: Acinetobacter baumannii-calcoaceticus complex (ABC) make a great burden
      on health-care systems due to hospital-acquired infections and antibacterial
      resistance. Aminoglycoside in combination with other antibacterials used as
      treatment options. However, ABC species overcome this class of antibacterials in
      different ways. This study provides a comprehensive report on the distribution of
      aminoglycoside modifying enzymes (AMEs) and 16S rRNA methylase in Acinetobacter
      baumannii and Acinetobacter nosocomialis isolated from various provinces in Iran.
      METHODS: During six month of study, from eight referral centers in seven
      provinces across the country, Iran, 178 A. baumannii and 43 A. nosocomialis
      isolates were collected. The minimum inhibitory concentration of amikacin,
      gentamicin, netilmicin, kanamycin and tobramycin were measured by microbroth
      dilution method. AMEs and 16S rRNA methylase variants were sought by PCR.
      RESULTS: High rates of resistance were seen in all centers. MIC50 and MIC90 for
      all A. baumannii and A. nosocomialis isolates from different centers were > 512
      mg/L. The most frequent AME was ant(3")-Ia (aadA1) in both of A. baumannii
      (74.1%) and A. nosocomialis (86%). armA was detected in A. baumannii and A.
      nosocomialis at the frequency of 41.6% and 67.4%, respectively. rmtA, B, C, D,
      aac(3)-Ia (aacC1) and aac(6')-Im were not detected, neither in A. baumannii nor
      A. nosocomialis. Moreover, aac(6')-Ih was only found in A. baumannii isolates.
      The distribution of some of the ARGs was limited to a definite center.
      CONCLUSION: The overall high-level carriage of ARGs in Acinetobacter species may
      limited usage of this class of antibacterials as a treatment option.

PMID- 30292706
TI  - Vaccination in Patients With Heart Disease. How Long Should We Wait?

PMID- 30292704
TI  - Combined Experimental and System-Level Analyses Reveal the Complex Regulatory
      Network of miR-124 during Human Neurogenesis.
AB  - Non-coding RNAs regulate many biological processes including neurogenesis. The
      brain-enriched miR-124 has been assigned as a key player of neuronal
      differentiation via its complex but little understood regulation of thousands of
      annotated targets. To systematically chart its regulatory functions, we used
      CRISPR/Cas9 gene editing to disrupt all six miR-124 alleles in human induced
      pluripotent stem cells. Upon neuronal induction, miR-124-deleted cells underwent
      neurogenesis and became functional neurons, albeit with altered morphology and
      neurotransmitter specification. Using RNA-induced-silencing-complex
      precipitation, we identified 98 high-confidence miR-124 targets, of which some
      directly led to decreased viability. By performing advanced transcription-factor
      network analysis, we identified indirect miR-124 effects on apoptosis, neuronal
      subtype differentiation, and the regulation of previously uncharacterized zinc
      finger transcription factors. Our data emphasize the need for combined
      experimental- and system-level analyses to comprehensively disentangle and reveal
      miRNA functions, including their involvement in the neurogenesis of diverse
      neuronal cell types found in the human brain.

PMID- 30292705
TI  - Geometry-Dependent Arrhythmias in Electrically Excitable Tissues.
AB  - Little is known about how individual cells sense the macroscopic geometry of
      their tissue environment. Here, we explore whether long-range electrical
      signaling can convey information on tissue geometry to individual cells. First,
      we studied an engineered electrically excitable cell line. Cells grown in
      patterned islands of different shapes showed remarkably diverse firing patterns
      under otherwise identical conditions, including regular spiking, period-doubling
      alternans, and arrhythmic firing. A Hodgkin-Huxley numerical model quantitatively
      reproduced these effects, showing how the macroscopic geometry affected the
      single-cell electrophysiology via the influence of gap junction-mediated
      electrical coupling. Qualitatively similar geometry-dependent dynamics were
      observed in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes.
      The cardiac results urge caution in translating observations of arrhythmia in
      vitro to predictions in vivo, where the tissue geometry is very different. We
      study how to extrapolate electrophysiological measurements between tissues with
      different geometries and different gap junction couplings.

PMID- 30292707
TI  - Carbon/Nitrogen Metabolic Balance: Lessons from Cyanobacteria.
AB  - Carbon and nitrogen are the two most abundant nutrient elements for all living
      organisms, and their metabolism is tightly coupled. What are the signaling
      mechanisms that cells use to sense and control the carbon/nitrogen (C/N)
      metabolic balance following environmental changes? Based on studies in
      cyanobacteria, it was found that 2-phosphoglycolate derived from the oxygenase
      activity of Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase) and 2
      oxoglutarate from the Krebs cycle act as the carbon- and nitrogen-starvation
      signals, respectively, and their concentration ratio likely reflects the status
      of the C/N metabolic balance. We will present and discuss the regulatory
      principles underlying the signaling mechanisms, which are likely to be conserved
      in other photosynthetic organisms. These concepts may also contribute to
      developments in the field of biofuel engineering or improvements in crop
      productivity.

PMID- 30292708
TI  - What to do if A + B doesn't work.
AB  - The majority of newborn resuscitations require very little beyond simple airway
      management and assisted ventilation. If cardiovascular collapse is serious enough
      to warrant additional support, resuscitation algorithms recommend moving to chest
      compressions and then on to medications and possibly volume replacement if vital
      signs remain marginal or absent. The evidence base upon which this part of the
      neonatal resuscitation algorithm is structured is sparse. Chest compressions and
      medications are rare interventions that do not lend themselves easily to clinical
      trials. Slowly but surely, however, the genesis of an empirical evidence base for
      this part of the algorithm is beginning to appear.

PMID- 30292709
TI  - Genetic predisposition to necrotizing enterocolitis in premature infants: Current
      knowledge, challenges, and future directions.
AB  - The role of genetics in the pathogenesis of necrotizing enterocolitis (NEC) was
      initially informed by epidemiological data indicating differences in prevalence
      among different ethnic groups as well as concordance in twins. These early
      observations, together with major advances in genomic research, paved the way for
      studies that begin to reveal the contribution of genetics to NEC. Using the
      candidate gene or pathway approach, several potential pathogenic variants for NEC
      in premature infants have already been identified. More recently, genome-wide
      association studies and exome-sequencing based studies for NEC have been
      reported. These advances, however, are tempered by the lack of adequately powered
      replication cohorts to validate the accuracy of these discoveries. Despite many
      challenges, genetic research in NEC is expected to increase, providing new
      insights into its pathogenesis and bringing the promise of personalized care
      closer to reality. In this review we provide a summary of genetic studies in NEC
      along with defining the challenges and possible future approaches.

PMID- 30292710
TI  - Sublingual Swelling due to Sublingual Immunotherapy.

PMID- 30292711
TI  - Failure of Adjustably Aligned Modular Radial Head Arthroplasty With Head-Neck
      Dissociation and Metallosis.
AB  - Radial head arthroplasty was introduced in 1941 and the literature supports
      satisfactory overall midterm patient outcomes and acceptable complication
      profiles with several models. There are several previously described mechanisms
      by which radial head complications typically occur. We present the case of a
      rarely described mechanism of radial head implant failure: elbow synovitis and
      pain from partial dissociation and metallosis in an adjustably aligned, modular,
      monopolar, mixed metal, press-fit radial head arthroplasty.

PMID- 30292712
TI  - Distal Dorsal Dimelia: A Disturbance of Dorsal-Ventral Digit Development.
AB  - PURPOSE: Congenital palmar nail (distal dorsal dimelia [dDD]) of the hand is a
      rare malformation most commonly affecting the little finger. The purpose of this
      report was to review the features and associations of this rare disorder and
      discuss the suspected underlying etiology in light of our current understanding
      of developmental biology. METHODS: In this retrospective cohort study from 3
      practices, we describe our collective experience and review the reported
      literature on this disorder both as an isolated condition and in conjunction with
      other anomalies. RESULTS: We examined 15 fingers with dDD, 5 of which involved
      little fingers. We also found dDD in 6 cases with radial polydactyly (preaxial
      polydactyl type II [PPD2]) and in 1 case of cleft hand involving digits adjacent
      to the clefted web space (the index and middle fingers). Cases of little finger
      dDD were also associated with prominent clefting of the adjacent web space in 4
      of 5 cases. All cases had stiffness of the interphalangeal joints and loss of
      palmar creases consistent with dorsalization of the palmar aspect of the digit.
      When combined with 63 fingers reported in the literature with dDD, 3 patterns
      were evident. The most common form occurred in little fingers (n = 50; 64%;
      dDDu). The next most common form was reported in association with cleft hands (n
      = 16; 21%; dDDc). Radial digits in association with either radial polydactyly
      (PPD2) or radial longitudinal deficiency were also susceptible to dDD (n = 12;
      15%; dDDr). CONCLUSIONS: Congenital dDD is a disturbance of terminal dorsal
      ventral digit patterning. The distribution of this condition with little fingers,
      clefting, and altered radial digit formation (PPD2 or radial longitudinal
      deficiency), as well as recent genetic and animal studies, suggests that dDD and
      altered dorsal-ventral patterning are linked to abnormal apical ectodermal ridge
      boundary formation. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.

PMID- 30292713
TI  - Multiple Stab Incisions and Evacuation Technique for Contrast Extravasation of
      the Hand and Forearm.
AB  - Extravasation of intravenous contrast agents in the hand and forearm during
      computed tomography scanning is rising with the use of automated pressure
      injectors. The main concern in such a situation is progression to acute
      compartment syndrome and necrosis of the overlying skin. Management has been
      mainly nonsurgical comprising upper limb elevation and orthosis, with surgical
      techniques such as liposuction and saline evacuation mainly used for large volume
      (>50 mL) extravasations. We have developed a technique of multiple stab incisions
      and drainage for the treatment of contrast extravasations.

PMID- 30292715
TI  - Thumb Amputations in Children: Classification and Reconstruction by Microsurgical
      Toe Transfers.
AB  - PURPOSE: Traumatic amputations of the thumb are rare in children compared with
      adults, but hand surgeons remain reticent to consider microsurgical
      reconstruction with toe-to-thumb transfers. This study reports the functional
      outcomes and complications of children with traumatic thumb amputations who
      underwent toe-to-thumb reconstruction. METHODS: A retrospective review of
      children who sustained thumb amputations and whose parents elected for their
      child to undergo reconstruction by toe-to-thumb transfer was performed. Details
      of the level of thumb amputation, whether other fingers were also amputated,
      which toe was transferred on which vascular pedicle, survival of the transfer,
      and complications, were collected. Opposition, sensation, and growth of the toe
      to-thumb transfers was measured. Functional and psychosocial outcomes were
      evaluated by both the parents and the older children using the Pediatric Outcomes
      Data Collection Instrument questionnaire. RESULTS: Twenty-one thumb amputations
      in 19 children between the ages of 2 and 17 years were referred for secondary
      reconstruction. Ten were isolated thumb amputations and 11 were combined thumb
      and multiple finger amputations. Two children had bilateral thumb amputations.
      Twenty-one toe-to-thumb transfers were performed: 14 second toe transfers and 7
      great toe transfers (3 great toe and 2 trimmed and 2 Morrison wraparound
      variations). There were no immediate postoperative reexplorations of the
      microsurgical anastomoses and all toe transfers survived completely. All children
      regained pinch and grasp function and sensation. There were no gait problems in
      the donor feet. CONCLUSIONS: Microsurgical toe-to-thumb transfers should be
      offered as an alternative option to the traditional techniques of distraction
      lengthening and pollicization, for posttraumatic thumb reconstruction in children
      for any level of amputation from just distal to the carpometacarpal joint to the
      interphalangeal joint. Toe-to-thumb transfer provides length, opposition, and
      sensation without disturbing ambulation and is associated with excellent
      psychosocial outcomes as evaluated by both parents and older children. TYPE OF
      STUDY/LEVEL OF EVIDENCE: IV.

PMID- 30292714
TI  - Factors Accounting for Variation in the Biomechanical Properties of Flexor Tendon
      Repairs.
AB  - PURPOSE: To investigate factors that cause variation in the mechanical properties
      of flexor tendon repairs. METHODS: One surgeon repaired 50 homogeneous absorbent
      sticks and 40 porcine flexor tendons with a simple loop, an Adelaide repair, a
      peripheral over-and-over repair, or a combination of the latter 2 repairs. Ten
      hand surgeons repaired 1 porcine flexor tendon with the combined Adelaide core
      and over-and-over peripheral repair. We loaded the samples statically until
      failure and calculated the variations caused by the testing process, tendon
      substance, and surgical performance in terms of yield and ultimate load. RESULTS:
      Tendon material and surgical performance both caused about half of the variation
      in the yield load of the combined repair. Surgical performance caused all
      variations observed in the ultimate load of the combined, peripheral-only, and
      core repairs. The effect of the tendon material was negligible in ultimate load.
      The intersurgeon variation was present only in yield load, and it represented one
      tenth of the total variation. CONCLUSIONS: The effect of tendon substance on
      variation of the ultimate load is minimal. In yield load, both tendon and
      surgical performance are responsible for the variation. CLINICAL RELEVANCE: In
      clinical realm, variation caused by testing is not present, but intersurgeon
      variation may cause additional variation in yield load. A hand surgeon cannot
      change the variation due to tendon properties, but with a more meticulous
      surgical technique, the variation related to the surgical performance can
      probably be diminished.

PMID- 30292716
TI  - Contact Mechanics of Anatomic Radial Head Prosthesis: Comparison Between Native
      Radial Head and Anatomic Radial Head Prostheses in the Dynamic Mode.
AB  - PURPOSE: The biomechanical characteristics of anatomic radial head prostheses
      have not been completely investigated. We compared and analyzed the contact
      kinematic characteristics of the native radial head and radial head prostheses
      replicating the native head contour, using a real-time flexion simulation model.
      METHODS: Ten fresh-frozen cadavers were used in this pilot study. A simulating
      dynamic motion mode from 0 degrees  to 130 degrees  of elbow flexion was applied.
      Radiocapitellar contact pressure and area were measured using a real-time
      digitized pressure sensor. Further, contact area and pressure curves were
      obtained during flexion, using a motion-tracking device. RESULTS: The mean
      contact area, mean contact pressure, and peak contact pressure of the native
      radial head and radial head prosthesis were 39 mm2, 0.0078 kgf/mm2, 0.0123
      kgf/mm2, and 33 mm2, 0.0093 kgf/dm2, 0.0148 kgf/mm2, respectively. The contact
      area and pressure curves were parabolic nonlinear for the radial head prosthesis
      and more linear for the native radial head. CONCLUSIONS: The radial head
      prosthesis mimics the mechanics of the native radial head in terms of mean
      contact area, mean contact pressure, and peak contact pressure; however,
      different patterns of contact pressure and area curves during elbow flexion
      extension were observed. CLINICAL RELEVANCE: We found that the biomechanics of
      the anatomic radial head prostheses used in the study were similar to those of
      the native radial head.

PMID- 30292717
TI  - Anatomy, Etiology, and Management of Scapular Winging.
AB  - Scapular winging is a painful and debilitating condition. The composite scapular
      motion of rotation, abduction, and tilting is necessary for proper shoulder
      function. Weakness or loss of scapular mechanics can lead to difficulties with
      elevation of the arm and lifting objects. The most common causes reported in the
      literature for scapular winging are dysfunction of the serratus anterior from
      long thoracic nerve injury causing medial winging or dysfunction of the trapezius
      from spinal accessory nerve injury causing lateral winging. Most reviews and
      teaching focus on these etiologies. However, acute traumatic tears of the
      serratus anterior, trapezius, and rhomboids off of the scapula are important and
      under-recognized causes of scapular winging and dysfunction. This article will
      review the relevant anatomy, etiology, clinical evaluation, diagnostic testing,
      and treatment of scapular winging. It will also discuss the differences in
      diagnosis and management between scapular winging arising from neurogenic causes
      and traumatic muscular detachment.

PMID- 30292718
TI  - H-reflex disinhibition by lumbar muscle inflammation in a mouse model of spinal
      cord injury.
AB  - Inflammation is a common comorbidity in patients with traumatic spinal cord
      injury (SCI). Recent reports indicate that inflammation hinders functional
      recovery in animal models of SCI. However, the spinal mechanisms underlying this
      alteration are currently unknown. Considering that spinal plasticity is a
      therapeutic target in patients and animal models of SCI, these mechanisms remain
      to be clarified. Using injections of complete Freund's adjuvant (CFA) in lumbar
      muscles as a model of persistent inflammation, the objective of this study was to
      assess the impact of inflammation on spinal reflex excitability after a complete
      midthoracic spinal transection in mice. To this end, the excitability of spinal
      reflexes was examined by measuring H-reflex frequency-dependent depression (FDD)
      on days 7, 14 and 28 following a complete spinal transection. H-reflex parameters
      were compared between spinal mice with CFA and control spinal mice. On day 7,
      lumbar muscle inflammation disinhibited the H-reflex, reflected by an attenuation
      of H-reflex FDD (p < 0.01), although this effect did not persist later on, either
      on day 14 or day 28. These results indicate that lumbar muscle inflammation
      alters spinal reflex excitability transiently in spinal mice. Considering that
      changes in spinal reflex excitability are associated with poor functional
      recovery after SCI, this implies that inflammation should be treated effectively
      to promote optimal recovery following SCI.

PMID- 30292719
TI  - A preliminary examination of the relation between neural sensitivity to reward
      and history of alcohol use disorder among adults with internalizing
      psychopathologies.
AB  - Decreased reward responsiveness, as demonstrated utilizing the event-related
      potential (ERP) component the reward positivity (RewP), is an established
      correlate of internalizing psychopathologies (IPs), such as depressive and
      anxiety disorders. Although IPs are highly comorbid with alcohol use disorders
      (AUDs) and despite evidence that AUDs are also characterized by aberrant reward
      processing styles, no studies have examined how AUD history impacts the RewP
      among adults with IPs. The current preliminary study sought to examine this
      question in a sample of 65 adults with 1) current IPs (i.e., depression, social
      anxiety, and/or generalized anxiety, 2) current IPs with a history of an AUD (IP
      + Past AUD), and 3) no history of a DSM-IV disorder. Participants completed a
      guessing reward task while electroencephalogram (EEG) was recorded. Results
      indicated that participants in the IP group exhibited a more attenuated RewP
      relative to IP + Past AUD and healthy control individuals. Findings from this
      study highlight the importance of examining diagnostic subgroups among adults
      with anxiety and depressive disorders, and suggest that a history of AUD may
      enhance reward reactivity at the neural level in individuals with IPs.

PMID- 30292720
TI  - Chronic antidepressant-like effect of EMD386088, a partial 5-HT6 receptor
      agonist, in olfactory bulbectomy model may be connected with BDNF and/or CREB
      signalling pathway.
AB  - BACKGROUND: The removal of the olfactory bulbs has been attributed to behavioral
      changes and neuroplasticity manifesting themselves among others like increases in
      brain neurotrophin expression and neurogenesis. Earlier data presented that
      EMD386088, a 5-HT6 receptor partial agonist, exerts antidepressant-like
      properties after chronic administration in olfactory bulbectomy (OB) model as was
      it compared with amitriptyline (AMI). The aim of this study was to compare acute
      and chronic biochemical effects of EMD386088, administered in its antidepressant
      active (2.5 mg/kg) and non-active (1.25 mg/kg) doses, found in the open field
      test in OB rats, with those of AMI (10 mg/kg).The levels of 5-HT6 receptor
      protein and selected neurotrophins in prefrontal cortex (PFC) and hippocampus
      (Hp) of rats have been examined. METHODS: 5-HT6 receptor protein and selected
      neurotrophins: brain-derived neurotrophic factor (BDNF), cAMP-response element
      binding protein (CREB), the product of the immediate early gene c-fos (cFos)
      protein levels were assessed using a Western blot analysis in PFC and Hp of
      bulbectomized rats after acute or chronic (14-day) EMD386088 or AMI
      intraperitoneal (ip) treatment. RESULTS: The acute treatment with EMD386088
      caused significant increases in CREB and BDNF protein levels in PFC, and an
      increase in BDNF in Hp of OB rats, while AMI injection decreased CREB and did not
      change BDNF levels. After the chronic administration of EMD386088, the increasing
      levels of BDNF and CREB were still observed in PFC and Hp. CONCLUSIONS: The
      antidepressant-like effect of EMD386088 may be associated with the
      neuroplasticity activation in PFC and Hp in rats.

PMID- 30292721
TI  - Involvement of transcription-coupled repair factor Mfd and DNA helicase UvrD in
      mutational processes in Pseudomonas putida.
AB  - Stalled RNA polymerases (RNAPs) pose an obstacle for the replicating complexes,
      which could lead to transcription-replication conflicts and result in genetic
      instability. Stalled RNAPs and DNA lesions blocking RNAP elongation are removed
      by transcription-coupled repair (TCR), the process which in bacteria is mediated
      by TCR factor Mfd and helicase UvrD. Although the mechanism of TCR has been
      extensively studied, its role in mutagenesis is still obscure. In the current
      study we have investigated the role of Mfd and UvrD in mutational processes in
      soil bacterium Pseudomonas putida. Our results revealed that UvrD helicase is
      essential to prevent the emergence of mutations, as the loss of uvrD resulted in
      elevated mutant frequency both in exponential- and stationary-phase bacterial
      cultures. UvrD was also found to be necessary to survive DNA damage, but NER or
      MMR pathways are not completely abolished in UvrD-deficient P. putida. Mfd
      deficiency had a moderate impact on surviving DNA damage and did not influence
      the frequency of mutations occurred in exponentially growing bacteria. However,
      the absence of Mfd caused approximately a two-fold decline in stationary-phase
      mutant frequency compared to the P. putida wild-type strain and suppressed the
      elevated mutant frequency observed in the DeltauvrD strain. Remarkably, the Mfd
      deficient strain also formed less UV-induced mutants. These results suggest that
      in P. putida the Mfd-mediated TCR could be associated with UV- and stationary
      phase mutagenesis.

PMID- 30292722
TI  - Effects of beta-subunit on gating of a potassium ion channel: Molecular
      simulations of cardiac IKs activation.
AB  - Dynamic conformational changes of ion channel proteins during activation gating
      determine their function as carriers of current. The relationship between these
      molecular movements and channel function over the physiological timescale of the
      action potential (AP) has not been fully established due to limitations of
      existing techniques. We constructed a library of possible cardiac IKs protein
      conformations and applied a combination of protein segmentation and energy
      linearization to study this relationship computationally. Simulations reproduced
      the effects of the beta-subunit (KCNE1) on the alpha-subunit (KCNQ1) dynamics and
      function, observed in experiments. Mechanistically, KCNE1 increased the
      probability of "visiting" conducting pore conformations on activation
      trajectories, thereby increasing IKs current. KCNE1 slowed IKs activation by
      impeding the voltage sensor (VS) movement and reducing its coupling to pore
      opening. Conformational changes along activation trajectories determined that the
      S4-S5 linker (S4S5L) plays an important role in these modulatory effects by
      KCNE1. Integration of these molecular structure-based IKs dynamics into a model
      of human cardiac ventricular myocyte, revealed that KCNQ1-KCNE1 interaction is
      essential for normal AP repolarization.

PMID- 30292723
TI  - Curcumin protects against diabetic cardiomyopathy by promoting autophagy and
      alleviating apoptosis.
AB  - The effects of curcumin on regulating cardiac apoptosis and autophagy were
      analyzed in diabetic models both in vivo and in vitro. In vivo, experimental
      diabetes was induced in mice by low-dose STZ injection combined with a high-fat
      diet. In vitro, cultured H9c2 cardiomyoblasts were exposed to high d-glucose
      concentrations combined with palmitate. Our results showed that apoptosis was
      increased and autophagy was suppressed in the hearts of diabetic mice, which was
      ameliorated by curcumin treatment, ultimately improving cardiac function.
      Moreover, the inhibition of autophagy exacerbated apoptotic death in cardiac
      cells under diabetic condition. Curcumin activated AMPK and JNK1, which
      phosphorylated Bcl-2 and Bim and subsequently disrupted their interactions with
      Beclin1, thereby promoting autophagy and alleviating apoptosis respectively. In
      addition, AMPK-mediated inhibition of mTORC1 pathway likely played a role in
      regulating autophagy by curcumin under diabetic condition. Our study suggests
      that curcumin protects against diabetic cardiomyopathy by modulating the
      crosstalk between autophagic and apoptotic machinery. Modulation of autophagy may
      be an effective strategy for the treatment of cardiovascular diseases associated
      with diabetes.

PMID- 30292724
TI  - Benefits of low vision aids to reading accessibility.
AB  - The Reading Accessibility Index (ACC) has been proposed as a single-value reading
      parameter that can capture information on both reading speed and print sizes that
      can be read. It is defined as the average reading speed across a relevant range
      of print sizes (1.3-0.4logMAR), normalised by typical young-adult reading speed
      of 200 wpm, and with values typically in the range of 0-1. This study determines
      the impact of low vision aids (LVAs) on reading by evaluating ACC values for
      visually impaired observers reading both without and with an optical LVA. A
      secondary analysis of previously published data obtained from 100 visually
      impaired observers attending low vision assessments was undertaken. Observers had
      mixed causes of visual impairment but predominantly macular degeneration. All
      used an LVA for reading, with 88% using it 'often' or 'very often'. MNREAD
      reading parameters, including ACC, were determined both for reading without an
      LVA (clinical function) and with the LVA habitually used for reading (aided
      function). There was a significant improvement in ACC from clinical (0.31) to
      aided conditions (0.47). Average improvement in ACC with an LVA was 0.16, but the
      benefits of LVAs in terms of improvement in ACC could not be predicted from
      clinical visual function. Even with an LVA reading accessibility is, on average,
      markedly reduced from normal levels. The ACC is a potentially valuable outcome
      measure for reading rehabilitation interventions.

PMID- 30292725
TI  - A comparison of tests for quantifying sensory eye dominance.
AB  - Clinicians rely heavily on stereoacuity to measure binocular visual function, but
      stereo-vision represents only one aspect of binocularity. Lab-based tests of
      sensory eye dominance (SED) are commonplace, but have not been translated to
      wider clinical practice. Here we compare several methods of quantifying SED in a
      format suitable for clinical use. We tested 30 participants with ostensibly
      normal vision on eight tests. Seven tests (#1-7) were designed to quantify SED in
      the form of an interocular balance-point (BP). In tests #1-6, we estimated a
      contrast-BP, the interocular difference in contrast required for observers to be
      equally likely to base their judgement on either eye, whereas in test #7 we
      measured binocular rivalry (interocular ratio of sensory dominance duration). We
      compare test-retest reliability (intra-observer consistency) and test-validity
      (inter-observer discriminatory power) and compare BP to stereoacuity (test #8).
      The test that best preserved inter-observer differences in contrast balance while
      maintaining good test-retest reliability was a polarity judgement using
      superimposed opposite-contrast polarity same-identity optotypes. A reliable and
      valid measure of SED can be obtained rapidly (20 trials) using a simple contrast
      polarity judgement. Tests that use polarity-rivalrous stimuli elicit more
      reliable judgments than those that do not. SIGNIFICANCE STATEMENT: Although
      sensory eye dominance is central to understanding normal and disordered binocular
      vision, there is currently no consensus as to the best way to measure it. Here we
      compare several candidate measures of sensory eye dominance and conclude that a
      reliable measure of SED can be achieved rapidly using a judgement of stimulus
      contrast-polarity.

PMID- 30292726
TI  - [Neonatal haemochromatosis: 10 years into a paradigm shift].

PMID- 30292727
TI  - [Neonate with cervical tumours].

PMID- 30292728
TI  - Promising neural diagnostic biomarkers and predictors of treatment outcomes for
      psychiatric disorders: Novel neuroimaging approaches.

PMID- 30292729
TI  - Association between increased retinal background noise and co-occurrent regular
      cannabis and alcohol use.
AB  - BACKGROUND: Cannabis consumption is widespread across the world, and the co
      occurrence of cannabis use and alcohol consumption is common. The study of
      background noise - resting-state neural activity, in the absence of stimulation -
      is an approach that could enable the neurotoxicity of these substances to be
      explored. Preliminary results have shown that delta-9-tetrahydrocannabinol
      (Delta9-THC) causes an increase in neural noise in the brain. Neurons in the
      brain and the retina share a neurotransmission system and have similar anatomical
      and functional properties. Retinal function, evaluated using an electroretinogram
      (ERG), may therefore reflect central neurochemistry. This study analyses retinal
      background noise in a population of regular co-occurrent cannabis and alcohol
      consumers. METHODS: We recorded the flash ERGs of 26 healthy controls and 45
      regular cannabis consumers, separated into two groups based on their alcohol
      consumption: less than or equal to 4 glasses per week (CU <= 4) or strictly >4
      glasses per week (CU >4). In order to extract the background noise, the Fourier
      transform of the pseudo-periodic and sinusoidal signals of the 3.0 flicker
      response sequence was calculated. This sequence represents the vertical
      transmission of the signal from cones to bipolar cells. The magnitude of the
      background noise is defined as the average of the magnitudes of the two
      neighbouring harmonics: harmonic -1 (low frequency noise) and harmonic +1 (high
      frequency noise). RESULTS: The magnitude of harmonic -1 was significantly
      increased between the groups CU > 4 (6.78 (+/-1.24)) and CU <= 4 (5.69 (+/-1.80))
      among regular users of cannabis and alcohol. A significant increase in the
      average magnitude of the two harmonics was found between the groups CU > 4 (5.12
      (+/-0.92)) and CU <= 4 (4.36 (+/-1.14)). No significant difference was observed
      with regard to the magnitude of the harmonic +1. CONCLUSIONS: The increase in
      background noise may reflect the neurotoxicity of cannabis, potentiated by
      alcohol consumption, on retinal neurons dynamic. This neural disruption of the
      response generated by retinal stimulation may be attributable to altered
      neurotransmitter release.

PMID- 30292730
TI  - Cooperation of the vestibular and cerebellar networks in anxiety disorders and
      depression.
AB  - The discipline of affective neuroscience is concerned with the neural bases of
      emotion and mood. The past decades have witnessed an explosion of research in
      affective neuroscience, increasing our knowledge of the brain areas involved in
      fear and anxiety. Besides the brain areas that are classically associated with
      emotional reactivity, accumulating evidence indicates that both the vestibular
      and cerebellar systems are involved not only in motor coordination but also
      influence both cognition and emotional regulation in humans and animal models.
      The cerebellar and the vestibular systems show the reciprocal connection with a
      myriad of anxiety and fear brain areas. Perception anticipation and action are
      also major centers of interest in cognitive neurosciences. The cerebellum is
      crucial for the development of an internal model of action and the vestibular
      system is relevant for perception, gravity-related balance, navigation and motor
      decision-making. Furthermore, there are close relationships between these two
      systems. With regard to the cooperation between the vestibular and cerebellar
      systems for the elaboration and the coordination of emotional cognitive and
      visceral responses, we propose that altering the function of one of the systems
      could provoke internal model disturbances and, as a result, anxiety disorders
      followed potentially with depressive states.

PMID- 30292731
TI  - Sleep Disorders.
AB  - Sleep disorders are frequent and can have serious consequences on patients'
      health and quality of life. While some sleep disorders are more challenging to
      treat, most can be easily managed with adequate interventions. We review the main
      diagnostic features of 6 major sleep disorders (insomnia, circadian rhythm
      disorders, sleep-disordered breathing, hypersomnia/narcolepsy, parasomnias, and
      restless legs syndrome/periodic limb movement disorder) to aid medical
      practitioners in screening and treating sleep disorders as part of clinical
      practice.

PMID- 30292732
TI  - Predictors of simulated driving performance in Huntington's disease.
AB  - BACKGROUND: As the disease progresses, patients with Huntington's disease (HD),
      an inherited neurodegenerative disorder, become less independent in their daily
      life activities and have to consider if they can still drive a car. For most
      patients, the decision to quit driving is difficult and affects their
      independence and social activities. OBJECTIVE: To investigate if cognitive,
      motor, or psychiatric symptoms can predict driving performance in HD gene
      carriers using a simulator situation. METHODS: Twenty-nine controls, 28
      premanifest HD, and 30 manifest HD participated in this observational, cross
      sectional study and underwent neuropsychological, motor, and psychiatric
      evaluations. All participants drove a motorway scenario in a driving simulator to
      evaluate driving performance. Group differences were analyzed using Analysis of
      Covariance and stepwise forward linear regression analysis was used to
      investigate which clinical assessments were predictors of driving simulator
      outcomes. RESULTS: Manifest HD drove slower and had less vehicle control in the
      driving simulator compared to controls and premanifest HD. They also performed
      worse on all clinical assessments compared to controls. Postural sway and slower
      speed of information processing were predictors of the driving simulator outcome
      measures. Psychiatric symptoms were unrelated to simulated driving. There were no
      significant differences between premanifest HD and controls. CONCLUSIONS:
      Increased postural sway and slower speed of processing are predictive of driving
      simulator performance in manifest HD. Worse performance on these clinical tasks
      might be useful as a first screening and could assist clinicians in their
      referral for an official on-road driving test.

PMID- 30292733
TI  - Single center experience with medical cannabis in Gilles de la Tourette syndrome.
AB  - INTRODUCTION: Patients with Gilles de la Tourette syndrome (GTS) experience
      reduced function and impaired quality of life. The current medical treatments for
      this syndrome can cause significant side effects and offer partial symptomatic
      relief. In a few small trials medical cannabis (MC) has been suggested to offer
      symptomatic relief with a relatively benign side effect profile. We conducted a
      real-life assessment of clinical benefit and adverse effects of chronic MC
      treatment among patients with GTS. METHODS: GTS patients treated with MC were
      interviewed via phone regarding treatment efficacy and side effect profile from
      chronic MC consumption. Global efficacy was rated on a Likert scale of 1-5 and
      side effects of treatment were recorded. RESULTS: Forty-Two GTS patients (33
      males, mean age 34.5) were interviewed for this study. The total global
      impression score of efficacy was 3.85 out of a total 5 possible points. Patients
      reported during the free discussion part of the interview about reduction in tic
      severity, better sleep and improved mood as positive effects of MC. Thirty-eight
      patients reported any kind of benefit from treatment while 10 patients with more
      than one year of consumption elected to stop treatment with MC for various
      reasons including severe side effects as psychosis in one patient. CONCLUSION: MC
      seems to hold promise in the treatment of GTS as it demonstrated high subjective
      satisfaction by most patients however not without side effects and should be
      further investigated as a treatment option for this syndrome.

PMID- 30292734
TI  - Impact of dyskinesia on activities of daily living in Parkinson's disease:
      Results from pooled phase 3 ADS-5102 clinical trials.
AB  - INTRODUCTION: In Parkinson's disease, dyskinesias result from disease progression
      and chronic levodopa therapy. Using Unified Dyskinesia Rating Scale (UDysRS) data
      pooled from two pivotal trials of ADS-5102 (amantadine) extended-release capsules
      in dyskinetic patients, we assessed the impact of dyskinesia on activities of
      daily living (ADLs), and the effects of ADS-5102 versus placebo. METHODS:
      Patients had troublesome dyskinesia (>=1 h/day) and at least mild functional
      impact of dyskinesia per Movement Disorder Society Unified Parkinson's Disease
      Rating Scale, Part IV, item 4.2. UDysRS Parts 1B, 3, and 4 scores at baseline
      were summarized descriptively. Twelve-week changes in score distributions and
      total scores were tested for significant differences between treatments. RESULTS:
      Among 196 patients, the majority (63%-73%) characterized their dyskinesia at
      baseline as having at least a mild impact on walking and balance; public and
      social settings; exciting or emotional settings; doing hobbies and other
      activities; handwriting; and dressing (six of ten ADLs in UDysRS Part 1B). By
      clinician ratings (in Parts 3 and 4), greatest impairment was most often observed
      in the trunk (62% of patients) and occurred most often for the ADL of dressing
      (64% had at least moderate impairment). ADS-5102 significantly reduced the
      patient-rated impact of dyskinesia on six of ten ADLs in Part 1B, the clinician
      rated intensity of dyskinesia in all seven body regions assessed in Part 3, and
      the clinician-rated disability during three of four ADL tasks assessed in Part 4.
      Improvements in Parts 1B, 3, and 4 total scores were also statistically
      significant. CONCLUSION: Dyskinesia can impair multiple tasks of daily living.
      Further studies may help characterize its underreported impact. By several
      measures, ADS-5102 treatment was associated with significant improvement of
      dyskinesias.

PMID- 30292735
TI  - A punch in the gut - Intestinal inflammation links environmental factors to
      neurodegeneration in Parkinson's disease.
AB  - Parkinson's disease (PD) is an etiologically heterogeneous disorder.
      Experimental, clinical and epidemiological data suggest that intestinal
      inflammation contributes to the pathogenesis of PD. This article reviews recent
      literature on gut microbiota and intestinal inflammation in PD. We propose that
      intestinal inflammation links environmental factors (e.g. an altered gut
      microbiota composition) to neurodegeneration in (genetically susceptible) PD
      patients. In addition, there is an epidemiological and genetic overlap between PD
      and inflammatory bowel disease. This overlap provides an opportunity to develop
      new treatment strategies for at least a subgroup of PD patients.

PMID- 30292736
TI  - Health-Related Quality of Life of Patients With Multiple Myeloma Treated in
      Routine Clinical Practice in France.
AB  - INTRODUCTION: New therapies for multiple myeloma (MM) have improved life
      expectancy, but health-related quality of life (HRQoL) data from patients with MM
      in the real-world setting are lacking. This study, conducted in France, explored
      the associations between treatment outcomes and HRQoL in patients with MM.
      PATIENTS AND METHODS: This observational, cross-sectional, multicenter study
      enrolled patients (>= 18 years old) with symptomatic MM who had consulted a
      physician at least once between February and March 2016. HRQoL was assessed using
      the European Organization for Research and Treatment of Cancer (EORTC) Core
      Quality of Life questionnaire (QLQ-C30) and the Quality of Life Multiple Myeloma
      module (QLQ-MY20). RESULTS: In total, 445 patients were included in the study;
      402 (90%) completed the EORTC QLQ-C30 and QLQ-MY20 questionnaires. HRQoL
      decreased significantly with treatment line. Patients in the first treatment-free
      interval had relatively high scores. At later lines, patients receiving active
      treatment had better scores than those whose treatment had ended. High EORTC QLQ
      C30 global health status scores were associated with good treatment response, few
      adverse events, and long duration of treatment, and were strongly influenced by
      the Eastern Cooperative Oncology Group performance status. Global health status
      scores correlated well with the 4 items of the QLQ-MY20 (future perspective,
      0.46; body image, 0.41; disease symptoms, -0.57; side effects of treatment, 
      0.53). CONCLUSION: Effective treatment options in MM can help maintain HRQoL by
      influencing treatment response levels and delaying disease progression.

PMID- 30292737
TI  - Interim Functional Imaging Is an Independent Predictor of Progression-free
      Survival in Advanced Classical Hodgkin Lymphoma - A Real-world Analysis.
AB  - BACKGROUND: Response-adapted therapy in advanced classical Hodgkin lymphoma (cHL)
      using interim functional imaging (IFI) is under active investigation. PATIENTS
      AND METHODS: We retrospectively examined patients with advanced cHL receiving 2
      front-line regimens stratified by IFI results at our institution. Time to
      endpoint analysis was estimated using the method of Kaplan-Meier with log ranks.
      Cox regression modeling was computed for multivariable analysis. RESULTS: A total
      of 124 patients with advanced cHL with a median follow up of 40.9 months were
      included. A total of 84 (67.7%) received ABVD (doxorubicin, bleomycin,
      vinblastine, and dacarbazine), whereas the remaining 40 (32.3%) received
      ABVD/eBEACOPP (escalated bleomycin, etoposide, doxorubicin, cyclophosphamide,
      vincristine, procarbazine, and prednisone). A positive IFI was seen in 36 (29%)
      patients. The corresponding 3-year progression free survival (PFS) stratified by
      IFI was 81.7% (95% confidence interval [CI], 70.1%-88.8%) versus 48.3% (95% CI,
      30.4%-64.1%) (P < .0001) for patients with negative or positive scan,
      respectively. Escalation to eBEACOPP from ABVD following a positive IFI resulted
      in a significantly higher 3-year PFS at 58.7% (95% CI, 0.3-0.79) versus 39.7%
      (95% CI, 0.18-0.61) respectively (P = .00015). Overall survival (OS) was similar
      across the groups (P = .44) irrespective of therapy received. At multivariable
      analysis, IFI was the only predictor of PFS with a hazard ratio of 4.6 (95% CI,
      1.9-10.8; P = .0008) whereas therapy escalation had a hazard ratio of 0.66 (95%
      CI, 0.14-3.4; P = .62). CONCLUSION: IFI is an independent predictor of PFS in
      advanced cHL and can guide therapeutic decisions in the real world. Given the
      inferior outcome seen in patients with a positive IFI, novel approaches of
      therapy are warranted.

PMID- 30292738
TI  - Persistent hypoxia following transvenous lead extraction with excimer laser.

PMID- 30292739
TI  - The beach chair position for shoulder surgery in intravenous general anesthesia
      and controlled hypotension: Impact on cerebral oxygenation, cerebral blood flow
      and neurobehavioral outcome.
AB  - STUDY OBJECTIVES: The aim of this study was to assess the impact of intravenous
      general anesthesia and controlled hypotension on cerebral saturation (rScO2),
      cerebral blood flow measured as middle cerebral artery blood flow velocity (Vmax
      MCA) and neurobehavioral outcome in patients scheduled for shoulder surgery in
      beach chair position. DESIGN: Prospective, assessor-blinded observational study.
      SETTING: University hospital, shoulder surgery operating room. PATIENTS: Forty
      ASA I-II patients scheduled for shoulder surgery in beach chair position and
      controlled hypotension. INTERVENTIONS: Neurological and neurobehavioral tests
      were performed prior and the day after surgery. The baseline data for near
      infrared spectroscopy, bispectral index, cerebral blood flow, PaCO2 and invasive
      blood pressure (radial artery) were taken prior anesthesia and after anesthesia
      induction, after beach chair positioning and all 20 min after surgery start until
      discharge of the patient. MEASUREMENTS: Neurological and neurobehavioral tests,
      cerebral saturation (rScO2) using near-infrared spectroscopy, BIS, cerebral blood
      flow using Doppler of the middle cerebral artery (Vmax MCA), PaCO2 and invasive
      blood pressure assessed at heart and at the external acoustic meatus level. MAIN
      RESULTS: The incidence of cerebral desaturation events (CDEs) was 25%. The blood
      pressure drop 5 min after beach chair position measured at the acoustic meatus
      level in the CDE group was higher compared to patients without CDEs (p = 0.009)
      as was the rScO2 (p = 0.039) and the Vmax MCA (p = 0.002). There were no
      neurological deficits but patients with CDEs showed a greater negative impact on
      neurobehavioral tests 24 h after surgery compared to patients without CDEs (p =
      0.001). CONCLUSIONS: In ASA I-II patients intravenous general anesthesia and
      controlled hypotension in the beach chair position affects cerebral blood flow
      and cerebral oxygenation with impact on the neurobehavioral outcome.

PMID- 30292740
TI  - PACU anesthesia liability data indicate safety of electroconvulsive therapy
      (ECT).

PMID- 30292741
TI  - Successful erector spinae plane block without ultrasound guidance in a severely
      cardiovascular compromised patient.

PMID- 30292742
TI  - Noradrenergic modulation determines respiratory network activity during
      temperature changes in the in vitro brainstem of bullfrogs.
AB  - Among vertebrate ectotherms, air breathing frequency is generally constrained
      across warmer temperatures, but decreases during cooling. The brainstem
      mechanisms that give rise to this ventilatory strategy are unclear.
      Neuromodulation has recently been shown to stabilize motor circuit output across
      temperatures. Therefore, we tested the hypothesis that an important
      neuromodulatory system in respiratory control network, norepinephrine, produces
      this pattern of respiratory motor activity across temperatures. To this end, we
      used in vitro brainstem-spinal cord preparations from adult bullfrogs, Lithobates
      catesbeianus, to assess the role of noradrenergic signaling in shaping the
      frequency response of the respiratory network during temperature changes. We
      identified that noradrenergic signaling through the alpha1 adrenergic receptor
      constrains motor output from the respiratory network across warm temperatures. In
      contrast, the alpha2 adrenergic receptor actively inhibits respiratory motor
      output during cooling. These results indicate that noradrenergic tuning, rather
      than passive thermal responses, produces temperature responses of the respiratory
      circuits.

PMID- 30292743
TI  - Adults with Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia:
      Considerations for Allogeneic Hematopoietic Cell Transplantation in First
      Complete Remission.
AB  - Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a
      subset of high-risk B cell ALLs. A large proportion of Ph-like ALL cases carry
      activating kinase mutations that could potentially allow them to be targeted by
      tyrosine kinase inhibitors. Ph-like ALL is not an uncommon entity, especially
      among adults, with a frequency exceeding 20%, including in older patients (>60
      years old) with ALL. Ph-like ALL is associated with inferior outcomes across all
      ages, and studies have consistently shown a higher incidence of persistent
      postinduction minimal residual disease in patients carrying Ph-like ALL compared
      with other subgroups of ALL, and this translates into inferior leukemia-related
      outcomes. The inferior outcome of conventional chemotherapy for Ph-like ALL in
      adults raises the fundamental question of whether all adults with Ph-like ALL
      require an allogeneic hematopoietic cell transplantation (HCT) in first complete
      remission (CR1) regardless of other presenting features and treatment response
      parameters. Here we present and discuss several scenarios in which adults with Ph
      like ALL underwent or were considered for HCT in CR1 for various reasons.
      Although the decision to proceed with HCT was clear and indisputable in some of
      these situations, in others we struggled with the decision to transplant in CR1
      because of the lack of published data regarding the efficacy of allogeneic HCT as
      consolidation for Ph-like ALL. We emphasize the urgent need for developing well
      designed studies to address this important question.

PMID- 30292744
TI  - A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Oral
      Brincidofovir for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell
      Transplantation.
AB  - Cytomegalovirus (CMV) infection is a common complication of allogeneic
      hematopoietic cell transplantation (HCT). In this trial, we randomized adult CMV
      seropositive HCT recipients without CMV viremia at screening 2:1 to receive
      brincidofovir or placebo until week 14 post-HCT. Randomization was stratified by
      center and risk of CMV infection. Patients were assessed weekly through week 15
      and every third week thereafter through week 24 post-HCT. Patients who developed
      clinically significant CMV infection (CS-CMVi; CMV viremia requiring preemptive
      therapy or CMV disease) discontinued the study drug and began anti-CMV treatment.
      The primary endpoint was the proportion of patients with CS-CMVi through week 24
      post-HCT; patients who discontinued the trial or with missing data were imputed
      as primary endpoint events. Between August 2013 and June 2015, 452 patients were
      randomized at a median of 15 days after HCT and received study drug. The
      proportion of patients who developed CS-CMVi or were imputed as having a primary
      endpoint event through week 24 was similar between brincidofovir-treated patients
      and placebo recipients (155 of 303 [51.2%] versus 78 of 149 [52.3%]; odds ratio,
      .95 [95% confidence interval, .64 to 1.41]; P = .805); fewer brincidofovir
      recipients developed CMV viremia through week 14 compared with placebo recipients
      (41.6%; P < .001). Serious adverse events were more frequent among brincidofovir
      recipients (57.1% versus 37.6%), driven by acute graft-versus-host disease (32.3%
      versus 6.0%) and diarrhea (6.9% versus 2.7%). Week 24 all-cause mortality was
      15.5% among brincidofovir recipients and 10.1% among placebo recipients.
      Brincidofovir did not reduce CS-CMVi by week 24 post-HCT and was associated with
      gastrointestinal toxicity.

PMID- 30292745
TI  - Over-expression of PD-1 Does Not Predict Leukemic Relapse after Allogeneic Stem
      Cell Transplantation.
AB  - Blockade of the T-cell exhaustion marker PD-1 to re-energize the immune response
      is emerging as a promising cancer treatment. Relapse of hematologic malignancy
      after allogeneic stem cell transplantation limits the success of this approach,
      and PD-1 blockade may hold therapeutic promise. However, PD-1 expression and its
      relationship with post-transplant relapse is poorly described. Because the donor
      immunity is activated by alloresponses, PD-1 expression may differ from
      nontransplanted individuals, and PD-1 blockade could risk graft-versus-host
      disease. Here we analyzed T-cell exhaustion marker kinetics and their
      relationship with leukemia relapse in 85 patients undergoing myeloablative T-cell
      depleted HLA-matched stem cell transplantation. At a median follow-up of 3.5
      years, 35 (44%) patients relapsed. PD-1 expression in CD4 and CD8 T cells was
      comparably elevated in relapsed and nonrelapsed cohorts. Helios+ regulatory T
      cells and CD8 effector memory cells at day 30 emerged as independent predictors
      of relapse. Although leukemia antigen-specific T cells did not overexpress PD-1,
      single-cell analysis revealed LAG3 and TIM3 overexpression at relapse. These
      findings indicate that PD-1 is an unreliable marker for leukemia-specific T-cell
      exhaustion in relapsing patients but implies other exhaustion markers and
      suppressor cells as relapse biomarkers.

PMID- 30292746
TI  - Late Mortality after Allogeneic Blood or Marrow Transplantation for Inborn Errors
      of Metabolism: A Report from the Blood or Marrow Transplant Survivor Study-2
      (BMTSS-2).
AB  - Allogeneic blood or marrow transplantation (BMT) is currently considered the
      standard of care for patients with specific inborn errors of metabolism (IEM).
      However, there is a paucity of studies describing long-term survival and cause
      specific late mortality after BMT in these patients with individual types of IEM.
      We studied 273 patients who had survived >=2 years after allogeneic BMT for IEM
      performed between 1974 and 2014. The most prevalent IEM in our cohort were X
      linked adrenoleukodystrophy (ALD; 37.3%), Hurler syndrome (35.1%), and
      metachromatic leukodystrophy (MLD; 10.2%). Conditional on surviving >=2 years
      after BMT, the overall survival for the entire cohort was 85.5 +/- 2.4% at 10
      years and 73.5 +/- 3.7% at 20 years. The cohort had a 29-fold increased risk of
      late death compared with an age- and sex-matched cohort from the general US
      population (95% CI, 22- to 38-fold). The increased relative mortality was highest
      in the 2- to 5-year period after BMT (standardized mortality ratio [SMR], 207;
      95% confidence interval [CI], 130 to 308) and declined with increasing time from
      BMT, but remained elevated for >=21 years after BMT (SMR, 9; 95% CI, 4 to 18).
      Sequelae from the progression of primary disease were the most common causes of
      late mortality in this cohort (76%). The use of T cell-depleted grafts in
      patients with ALD and Hurler syndrome was a risk factor for late mortality.
      Younger age at BMT and use of busulfan and cyclosporine were protective in
      patients with Hurler syndrome. Our findings demonstrate relatively favorable
      overall survival in >=2-year survivors of allogeneic BMT for IEM, although
      primary disease progression continues to be responsible for the majority of late
      deaths.

PMID- 30292747
TI  - Survival and Functional Outcomes in Boys with Cerebral Adrenoleukodystrophy with
      and without Hematopoietic Stem Cell Transplantation.
AB  - Cerebral adrenoleukodystrophy (CALD) is a rapidly progressing, often fatal
      neurodegenerative disease caused by mutations in the ABCD1 gene, resulting in
      deficiency of ALD protein. Clinical benefit has been reported following
      allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a large
      multicenter retrospective chart review to characterize the natural history of
      CALD, to describe outcomes after HSCT, and to identify predictors of treatment
      outcomes. Major functional disabilities (MFDs) were identified as having the most
      significant impact on patients' abilities to function independently and were used
      to assess HSCT outcome. Neurologic function score (NFS) and Loes magnetic
      resonance imaging score were assessed. Data were collected on 72 patients with
      CALD who did not undergo HSCT (untreated cohort) and on 65 patients who underwent
      transplantation (HSCT cohort) at 5 clinical sites. Kaplan-Meier (KM) estimates of
      5-year overall survival (OS) from the time of CALD diagnosis were 55% (95%
      confidence interval [CI], 42.2% to 65.7%) for the untreated cohort and 78% (95%
      CI, 64% to 86.6%) for the HSCT cohort overall (P = .01). KM estimates of 2-year
      MFD-free survival for patients with gadolinium-enhanced lesions (GdE+) were 29%
      (95% CI, 11.7% to 48.2%) for untreated patients (n = 21). For patients who
      underwent HSCT with GdE+ at baseline, with an NFS <=1 and Loes score of 0.5 to
      <=9 (n = 27), the 2-year MFD-free survival was 84% (95% CI, 62.3% to 93.6%).
      Mortality rates post-HSCT were 8% (5 of 65) at 100 days and 18% (12 of 65) at 1
      year, with disease progression (44%; 7 of 16) and infection (31%; 5 of 16) listed
      as the most common causes of death. Adverse events post-HSCT included infection
      (29%; 19 of 65), acute grade II-IV graft-versus-host disease (GVHD) (31%; 18 of
      58), and chronic GVHD (7%; 4 of 58). Eighteen percent of the patients (12 of 65)
      experienced engraftment failure after their first HSCT. Positive predictors of OS
      in the HSCT cohort may include donor-recipient HLA matching and lack of GVHD, and
      early disease treatment was predictive of MFD-free survival. GdE+ status is a
      strong predictor of disease progression in untreated patients. This study
      confirms HSCT as an effective treatment for CALD when performed early. We propose
      survival without MFDs as a relevant treatment goal, rather than solely assessing
      OS as an indicator of treatment success.

PMID- 30292748
TI  - Process control and in vitro/in vivo evaluation of aripiprazole sustained-release
      microcrystals for intramuscular injection.
AB  - This work describes the preparation of aripiprazole sustained-release
      microcrystals for intramuscular injection, through recrystallization, drying, wet
      grinding, and solidification steps, which had a great impact on the product
      quality. Here, we evaluated the crystal form of the drug in each step by
      differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and
      fourier transform infrared spectroscopy (FT-IR), demonstrating that there is no
      change in the crystal form of aripiprazole monohydrate (H1) during grinding and
      freeze-drying. Microscopy and scanning electron microscopy (SEM) data showed that
      freeze-drying had no effect on the morphology of milled H1, and thermal
      gravimetric analysis (TGA) results showed that the freeze-dried formulation had
      acceptable water content. In particular, in this study, a similarity factor
      fitting was applied to determine the similarity of the particle size cumulative
      distribution curve, and the similarity factor value (99.00) showed that there was
      no change in the particle size distribution before and after freeze-drying. A two
      chamber transmembrane method was used to investigate the in vitro release of the
      aripiprazole sustained-release microcrystal (ALSI) and commercial preparations
      (Abilify Maintena(r)). The similarity factor fitting of in vitro release profiles
      and drug cumulative release curves in vivo yielded similarity factor values of
      98.00 and 95.43, respectively, indicating similar in vitro release and in vivo
      bioavailability of rats between the ALSI and Abilify Maintena(r). A single-dose
      administration could produce long-term effects for a month. For a
      microcrystalline suspension, in addition to the conventional quality control
      indicators, the similarity of the cumulative particle size distribution, the in
      vitro release profile, and the similarity of the drug release percentage in vivo
      can be used to reflect product quality and process control.

PMID- 30292749
TI  - A novel multivalent DNA helix-based inhibitor showed enhanced anti-HIV-1 fusion
      activity.
AB  - DNA helix-based HIV-1 fusion inhibitors have been discovered as potent drug
      candidates, but further research is required to enhance their efficiency. The
      trimeric structure of the HIV-1 envelope glycoprotein provides a structural basis
      for multivalent drug design. In this work, a "multi-domain" strategy was adopted
      for design of an oligodeoxynucleotide with assembly, linkage, and activity
      domains. Built on the self-assembly of higher-order nucleic acid structure, a
      novel category of multivalent DNA helix-based HIV-1 fusion inhibitor could be
      easily obtained by a simple annealing course in solution buffer, with no other
      chemical synthesis for multivalent connection. An optimized multivalent molecule,
      M4, showed significantly higher anti-HIV-1 fusion activity than did corresponding
      monovalent inhibitors. Examination of the underlying mechanism indicated that M4
      could interact with HIV-1 glycoproteins gp120 and gp41, thereby inhibiting 6HB
      formation in the fusion course. M4 also showed anti-RDDP and anti-RNase H
      activity of reverse transcriptase. Besides, these assembled molecules showed
      improved in vitro metabolic stability in liver homogenate, kidney homogenate, and
      rat plasma. Moreover, little acute toxicity was observed. Our findings aid in the
      structural design and understanding of the mechanisms of DNA helix-based HIV-1
      inhibitors. This study also provides a general strategy based on a new structural
      paradigm for the design of other multivalent nucleic acid drugs.

PMID- 30292750
TI  - Nanostructured lipid carriers versus solid lipid nanoparticles for the potential
      treatment of pulmonary hypertension via nebulization.
AB  - With the non-selective vasodilating action, short half-life and first-pass
      metabolism of sildenafil (SC), local application in the lung for pulmonary
      arterial hypertension is of high demand. Although several nanosystems have been
      lately investigated, nanostructured lipid carriers (NLCs) give promises of
      potential safety, biodegradability and controlled drug release. In the current
      study, NLCs comprising either precirol, stearic acid or beeswax as solid lipid in
      presence of oleic acid as liquid lipid and PVA or poloxamer as emulsifier were
      prepared. Optimized NLCs (200-268 nm in size) were appraised versus SLNs both in
      vitro and in vivo. Precirol/PVA-based SLNs and NLCs ensued high entrapment
      efficiencies (EE > 95%) and controlled release behaviour over 6 h even though
      NLCs showed higher release profile. Stability studies at 4  degrees C indicated
      potential colloidal and entrapment stability over 3 months. Interestingly, NLCs
      demonstrated efficient nebulization, low interaction with mucin and higher
      viability of A549 cells (3-fold increase in IC50 relative to SLNs) providing good
      aptitudes for pulmonary application. In vivo administration of free SC in rats
      revealed localized intra-alveolar bleeding, presumably related to excessive
      vasodilatation. Meanwhile, the nanoencapsulated drug confirmed normal lung
      parenchyma with minimal incidence of bleeding. Inspiring results highlight the
      potential of sildenafil-laden nanostructured lipid carriers as pulmonary drug
      delivery system.

PMID- 30292751
TI  - Risk analysis and seroprevalence of HEV in people living with HIV/AIDS in Brazil.
AB  - Acute Hepatitis E virus (HEV) infection in people living with HIV/AIDS (PLHA) can
      lead to fulminant hepatic failure, cirrhosis and death. The prevalence of anti
      HEV antibodies within this group varies according to the geographical area.
      However, in South America, studies concerning the detection of HEV in PLHA are
      rare. Here, we investigated the presence of HEV by serological and molecular
      detection and evaluated the risk factors associated with infection in PLHA in
      Pernambuco state, Brazilian Northeast. Serological and molecular detection of HEV
      was performed in 366 samples of PLHA by ELISA for anti-HEV IgG and RT-PCR,
      respectively. Anti-HEV IgG prevalence was 4.1% (15/366) and no HEV RNA was
      detected. Concerning the risk factors, we evaluated, in multivariable analysis,
      age, years of school, sexual orientation, oral-anal sex, use of injectable drugs
      and piped water. Among them, only piped water availability could be associated
      with the HEV infection in PLHA (OR: 0.08; CI 95%: 0.01-0.66; p = 0.0182). This
      study showed for the first time the association of piped water as protection
      factor for HEV infection in PLHA. Finally, this is also the first report of HEV
      seroprevalence in PLHA in the Northeast Brazil.

PMID- 30292752
TI  - Resorption behaviour of the articular surface dome and functional outcome after
      open reduction and internal fixation of mandibular condylar head fractures using
      small-fragment positional screws.
AB  - PURPOSE: The aim of the study was to evaluate the resorption of the mandibular
      condylar head after open reduction and internal fixation of fractures with small
      fragment screws and to evaluate the functional outcome. PATIENTS AND METHOD:
      Forty-eight patients (55 condylar head fractures) underwent surgical treatment.
      All kinds of complications were recorded. In a subgroup of 20 patients, the
      average loss of bone height of the condylar head joint surface was gauged by
      measuring the vertical distances from 3 selected reference points of the fixation
      hardware to the vertex of the condyle in views of multiplanar radiographs after 6
      months. Functional outcome was analysed by Helkimo index score. RESULTS:
      Complication rates were low. Osteosynthesis loosening occurred in 4 cases. The
      mean bone resorption along the condylar head joint surface in the subgroup of 20
      patients (with 23 joints) was 0.7 mm. Functional outcome was rated as follows: 8
      patients - good, 11 patients - slightly impaired, 1 patient - moderately
      impaired. CONCLUSION: Open reduction and internal fixation of condylar head
      fractures with small-fragment screws leads to reliable results in terms of joint
      surfaces relatively resistant to resorption and function. Low bone resorption on
      the joint surface of the condylar head can be expected.

PMID- 30292753
TI  - Expression of the alternative splicing variants of bcl6b in medaka Oryzias
      latipes.
AB  - Bcl6B, also known as BAZF, plays important roles in the immune response,
      repression of cancers, and maintenance of spermatogonial stem cells in mammals.
      In this study, the homologous gene bcl6b and its 5 alternative splicing variants,
      namely bcl6bX1 to bcl6bX5, were isolated from medaka fish, Oryzias latipes.
      Medaka bcl6b possesses conserved domains such as BTB domain, RD2 domain and four
      zinc fingers. Medaka bcl6bX1 to bcl6bX3 possess all three previously mentioned
      domains with minor differences in sequences. Medaka bcl6bX4 possesses only the
      BTB domain due to premature stopping, and bcl6bX5 possesses both the BTB domain
      and zinc fingers without the RD2 domain. Medaka bcl6b was expressed in the
      tissues including the brain, heart, gill, muscle, spleen, kidney, intestine,
      ovary and testes of adult fish. Medaka bcl6b was expressed in the embryos from
      very early stage, and could be detected clearly in the developing eyes by RT-PCR
      and in situ hybridization. Medaka bcl6b could respond to the stimuli of polyI:C
      and LPS in the kidney and spleen. Medaka bcl6bX1 to bcl6bX3 were the majority of
      the variants expressed in the adult tissues and the embryos, and were the major
      response to the stimulation of polyI:C and LPS in the spleen. These results
      suggested that bcl6b, including its isoforms, could function in various tissues
      and embryogenesis. Moreover, bcl6b might be a factor for immune response in
      medaka.

PMID- 30292754
TI  - Expression patterns and ligand binding characterization of Plus-C odorant-binding
      protein 14 from Adelphocoris lineolatus (Goeze).
AB  - Odorant-binding proteins (OBPs) can bind and transport hydrophobic odorants
      across the sensillum lymph to the olfactory receptors (ORs) and play crucial
      roles in insect chemosensory systems. Although the ligand spectra of classical
      OBPs have been extensively characterized, little is known about OBPs in the Plus
      C subgroup. Here, we focus on AlinOBP14, a Plus-C OBP from the hemipteran mirid
      bug pest Adelphocoris lineolatus (Goeze). Quantitative real-time PCR experiments
      suggest that AlinOBP14 is ubiquitously expressed at different developmental
      stages but is highly expressed in the adult head, the non-chemosensory organ.
      Fluorescence-based competitive binding assays show that beta-ionone, nerolidol,
      farnesol and insect juvenile hormone III (JHIII) strongly bind to AlinOBP14. No
      significant internal binding pocket is predicted by homology modeling. Instead,
      the long N-terminal and C-terminal regions and parts of several alpha-helixes
      form a cupped cavity to accommodate ligands. Molecular docking reveals that the
      four potential ligands have distinct binding orientations, implying different
      roles of the N-terminal extension in ligand recognition. This hypothesis is
      further confirmed via a ligand binding assay in which the recombinant N-terminal
      mutant AlinOBP14 displays comparable binding affinities for beta-ionone and
      trans, trans-farnesol but decreased binding affinities for nerolidol and JHIII.
      Thus, our current study is the first to characterize the ligand binding spectra
      of a Plus-C OBP in hemipteran insect species and reveals that N-terminal
      extensions could be required for its recognition of putative ligands.

PMID- 30292755
TI  - A novel selenonucleoside suppresses tumor growth by targeting Skp2 degradation in
      paclitaxel-resistant prostate cancer.
AB  - Prostate cancer (PC) is the most common disease in men over age 50, and its
      prevalence rate has been gradually increasing since 1980. Taxane-derived
      anticancer agents are the primary agents used to treat metastatic prostate cancer
      patients; however, the side effects and acquired drug resistance limit the
      success of these therapies. Because there is no specific treatment for paclitaxel
      resistant prostate cancer, it is necessary to develop new targets and therapeutic
      strategies to overcome the acquired resistance. In this study, the antitumor
      activity of a novel selenonucleoside (4'-selenofuranosyl-2,6-dichloropurine, LJ
      2618), a third-generation nucleoside, and its plausible mechanisms of action in
      paclitaxel-resistant prostate cancer (PC-3-Pa) cells were investigated. The
      established PC-3-Pa cells exhibited over 100-fold resistance against paclitaxel
      compared to the paclitaxel-sensitive PC-3 cells. LJ-2618, however, effectively
      inhibited the proliferation of both cell lines with similar IC50 values in vitro.
      In PC-3-Pa cells, the activated PI3K/Akt signaling pathway was suppressed by LJ
      2618 treatment. In addition, Skp2 was found to be over-expressed in paclitaxel
      resistant cells, and the transfection of Skp2 siRNA recovered the sensitivity of
      paclitaxel in PC-3-Pa cells. Furthermore, LJ-2618 significantly down-regulated
      Skp2 expression in PC-3-Pa cells by promoting degradation and inducing
      destabilization of Skp2, which triggers G2/M cell cycle arrest. In a xenograft
      mouse model implanted with PC-3-Pa cells, LJ-2618 (3 or 10 mg/kg) effectively
      inhibited tumor growth with the enhancement of Skp2 degradation and induction of
      p27 expression in tumor tissues. These findings suggest that LJ-2618 may have
      potential for overcoming paclitaxel resistance via promoting Skp2 degradation and
      stabilizing p27 expression in PC-3-Pa cells. Therefore, the novel
      selenonucleoside LJ-2618 may lead to the development of a new treatment strategy
      for patients with paclitaxel-resistant, castration-resistant prostate cancer.

PMID- 30292756
TI  - Probing structure-activity relationship in beta-arrestin2 recruitment of
      diversely substituted adenosine derivatives.
AB  - In the adenosine receptor (AR) subfamily of G protein-coupled receptors (GPCRs),
      biased agonism has been described for the human A1AR, A2BAR and A3AR. While
      diverse A3AR agonists have been evaluated for receptor binding and Gi-mediated
      cAMP signalling, the beta-arrestin2 (betaarr2) pathway has been left largely
      unexplored. We screened nineteen diverse adenosine derivatives for betaarr2
      recruitment using a stable hA3AR-NanoBit(r)-betaarr2 HEK293T cell line. Their
      activity profiles were compared with a cAMP accumulation assay in stable hA3AR
      CHO cells. Structural features linked to betaarr2 activation were further
      investigated by the evaluation of an additional ten A3AR ligands. The A3AR
      selective reference agonist 2-Cl-IB-MECA, which is a full agonist in terms of
      cAMP inhibition, only showed partial agonist behaviour in betaarr2 recruitment.
      Highly A3AR-selective (N)-methanocarba 5'-uronamide adenosine derivatives
      displayed higher potency in both cAMP signalling and betaarr2 recruitment than
      reference agonists NECA and 2-Cl-IB-MECA. Their A3AR-preferred conformation
      tolerates C2-position substitutions, for increased betaarr2 efficacy, better than
      the flexible scaffolds of ribose derivatives. The different amino functionalities
      in the adenosine scaffold of these derivatives each seem to be important for
      signalling as well. In conclusion, we have provided insights into ligand features
      that can help to guide the future therapeutic development of biased A3AR ligands
      with respect to G-protein and betaarr2 signalling.

PMID- 30292757
TI  - C-terminal degradation of PYY peptides in plasma abolishes effects on satiety and
      beta-cell function.
AB  - The importance of dipeptidyl peptidase-4 mediated N-terminal metabolism of the
      enteroendocrine-derived hormone, peptide YY (PYY), for receptor binding and
      subsequent biological action profile is well established. However, an intact C
      terminus may be fundamental also for bioactivity of PYY peptides. The current
      study has demonstrated C-terminal degradation of the major recognised circulating
      forms of PYY, PYY(1-36) and PYY(3-36), in plasma, resulting in production of
      PYY(1-34) and PYY(3-34). Interestingly, the angiotensin-converting-enzyme (ACE)
      inhibitor, captopril, blocked formation of PYY(3-34) from PYY(3-36) in plasma,
      but did result in the appearance of PYY(3-35). In addition, we were able to
      evidence C-terminal truncation of PYY(1-35) and PYY(3-35) to PYY(1-34) and PYY(3
      34), respectively. As expected, PYY(1-36) and PYY(3-36) inhibited (P < 0.05-P <
      0.001) glucose- and alanine-stimulated insulin secretion from BRIN-BD11 beta
      cells. In contrast, PYY(1-34), PYY(3-34), PYY(1-35) and PYY(3-35) were devoid of
      insulinostatic actions. Both PYY(1-36) and PYY(3-36), but not related PYY
      metabolites, significantly (P < 0.05-P < 0.001) enhanced proliferation of BRIN
      BD11 and 1.1B4 beta-cell lines, and protected (P < 0.01-P < 0.001) these cell
      lines against cytokine-induced apoptosis. As expected, PYY(3-36) induced clear (P
      < 0.05-P < 0.01) appetite suppressive effects in mice, but this action was
      eliminated by mono- or di-peptide C-terminal truncation. Interestingly, captopril
      significantly (P < 0.05) augmented the anorexigenic effects of PYY(3-36) in mice.
      PYY(1-36), PYY(3-36), PYY(1-34) and PYY(3-34) lacked effects on in vivo glucose
      tolerance or glucose-induced insulin release. Taken together, these data
      highlight the unrecognised importance of C-terminal integrity of PYY peptides for
      biological activity and therapeutic usefulness in obesity-diabetes.

PMID- 30292758
TI  - CT Imaging-Based Low-Attenuation Super Clusters in Three Dimensions and the
      Progression of Emphysema.
AB  - BACKGROUND: Distributions of low-attenuation areas in two-dimensional (2-D) CT
      lung slices are used to quantify parenchymal destruction in patients with COPD.
      However, these segmental approaches are limited and may not reflect the true
      three-dimensional (3-D) tissue processes that drive emphysematous changes in the
      lung. The goal of this study was to instead evaluate distributions of 3-D low
      attenuation volumes, which we hypothesized would follow a power law distribution
      and provide a more complete assessment of the mechanisms underlying disease
      progression. METHODS: CT scans and pulmonary function test results were acquired
      from an observational database for N = 12 patients with COPD and N = 12 control
      patients. The data set included baseline and two annual follow-up evaluations in
      patients with COPD. Three-dimensional representations of the lungs were
      reconstructed from 2-D axial CT slices, with low-attenuation volumes identified
      as contiguous voxels < -960 Hounsfield units. RESULTS: Low-attenuation sizes
      generally followed a power law distribution, with the exception of large,
      individual outliers termed "super clusters," which deviated from the expected
      distribution. Super cluster volume was correlated with disease severity (% total
      low attenuation, rho = 0.950) and clinical measures of lung function including
      FEV1 (rho = -0.849) and diffusing capacity of the lung for carbon monoxide Dlco
      (rho = -0.874). To interpret these results, we developed a personalized
      computational model of super cluster emergence. Simulations indicated disease
      progression was more likely to occur near existing emphysematous regions, giving
      rise to a biomechanical, force-induced mechanism of super cluster growth.
      CONCLUSIONS: Low-attenuation super clusters are defining, quantitative features
      of parenchymal destruction that dominate disease progression, particularly in
      advanced COPD.

PMID- 30292759
TI  - A simple clinical risk score (C2HEST) for predicting incident atrial fibrillation
      in Asian subjects: Derivation in 471,446 Chinese subjects, with internal
      validation and external application in 451,199 Korean subjects.
AB  - BACKGROUND: The incidence of atrial fibrillation (AF) is increasing, conferring a
      major healthcare issue in Asia. No risk score for predicting incident AF has been
      specifically developed in Asian subjects. Our aim was to investigate risk factors
      for incident AF in Asian subjects and to combine them into a simple clinical risk
      score. METHODS: Risk factors for incident AF were analyzed in 471,446 subjects
      from the Chinese Yunnan Insurance Database (internal derivation cohort), and then
      combined into a simple clinical risk score. External application of the new score
      was performed in 451,199 subjects from the Korean National Health Insurance
      Service (external cohort). RESULTS: In the internal cohort, structural heart
      disease (SHD), heart failure (HF), age>=75 years, coronary artery disease (CAD),
      hyperthyroidism, chronic obstructive pulmonary disease (COPD) and hypertension
      were associated with incident AF. Given the low prevalence and the strong
      association of SHD with incident AF (hazard ratio: 26.07 [18.22-37.30], p<0.001),
      these patients should be independently considered as 'high-risk' for AF and were
      excluded from the analysis. The remaining predictors were combined into the new
      simple C2HEST score: C2: CAD / COPD (1 point each); H: Hypertension; E: Elderly
      (Age>=75, doubled); S: Systolic HF (doubled); T: Thyroid disease
      (hyperthyroidism). The C2HEST score showed good discrimination with AUC 0.75
      [0.73-0.77] and had good calibration (p=0.774). The score was internally
      validated by bootstrap sampling procedure, giving an AUC of 0.75 [0.73-0.77].
      External application gave an AUC of 0.65 [0.65-0.66]. The C2HEST score was
      superior to CHADS2 and CHA2DS2VASc scores in both cohorts in predicting incident
      AF. CONCLUSIONS: We have developed and validated the C2HEST score as a simple
      clinical tool to assess the individual risk of developing AF in the Asian
      population without SHD.

PMID- 30292760
TI  - Safety and Efficacy of Remimazolam Compared to Placebo and Midazolam for Moderate
      Sedation during Bronchoscopy.
AB  - BACKGROUND: While the complexity of flexible bronchoscopy has increased, standard
      options for moderate sedation medications have not changed in three decades.
      There is need to improve moderate sedation while maintaining safety. Remimazolam
      was developed to address shortcomings of current sedation strategies. METHODS: A
      prospective, double-blind, randomized, multi-center, parallel group trial was
      performed at 30 U.S. sites. The efficacy and safety of remimazolam for sedation
      during flexible bronchoscopy were compared to placebo and open-label midazolam.
      RESULTS: The success rates were 80.6% in the remimazolam arm, 4.8% in the placebo
      arm (p<0.0001), and 32.9% in the midazolam arm. Bronchoscopy was started sooner
      in the remimazolam arm (mean 6.4+/-5.82 minutes) compared to placebo (17.2+/-4.15
      minutes, p<0.0001), and midazolam (16.3+/-8.60 minutes). Time to full alertness
      after the end of bronchoscopy was significantly shorter in patients treated with
      remimazolam (median 6.0 minutes, 95% CI: 5.2; 7.1) compared to those treated with
      placebo (13.6 minutes, 95% CI: 8.1; 24.0; p=0.0001) and midazolam (12.0 minutes,
      95% CI: 5.0; 15.0). Remimazolam registered superior restoration of
      neuropsychiatric function compared to placebo and midazolam. Safety was
      comparable among all 3 arms, and 5.6% of the patients in the remimazolam group
      had serious Treatment Emergent Adverse Events (TEAEs) as compared to 6.8% in the
      placebo group. CONCLUSIONS: Remimazolam administered under supervision of a
      pulmonologist was effective and safe for moderate sedation during flexible
      bronchoscopy. In an exploratory analysis, it demonstrated a shorter onset of
      action and faster neuropsychiatric recovery than midazolam.

PMID- 30292762
TI  - Asthma and immunology: a call for papers for AAAAI.

PMID- 30292761
TI  - Evidence for an Association Between Intrahepatic Vascular Changes and the
      Development of Hepatopulmonary Syndrome.
AB  - BACKGROUND: Hepatopulmonary syndrome (HPS) is characterized by an arterial
      oxygenation defect, defined by an increased alveolar-arterial oxygen gradient,
      induced by pulmonary vascular dilatations in the context of liver disease. The
      pathogenesis of HPS is poorly understood. Morphologic changes associated with HPS
      are unknown. This study aimed at describing imaging and pathology changes
      associated with HPS. METHODS: We performed a case-control study in candidates for
      transplant with suspicion of cirrhosis. Each patient with HPS (Pao2 <= 70 mm Hg)
      was matched to three control subjects for age, cause, and liver disease severity.
      Pretransplant thoracic and abdominal imaging and explanted livers were reviewed.
      RESULTS: CT scans and Doppler ultrasounds from 21 patients with HPS were compared
      with those from 63 control subjects. HPS was associated with a two- to threefold
      higher prevalence of obstructed intrahepatic portal branches, of slowed or
      hepatofugal portal blood flow, and of large abdominal portosystemic shunts.
      Hepatic artery diameter was also larger in patients with HPS. Explanted livers
      from 19 patients with HPS were compared with those from 57 control subjects. HPS
      was associated with a fourfold higher prevalence of portal venule thrombosis and
      a ninefold higher prevalence of extensive vascular proliferation within fibrous
      septa. Obstruction of centrilobular venules, sinusoidal dilatation, and liver
      parenchymal extinction were also more common in patients with HPS. CONCLUSIONS:
      HPS is associated with intrahepatic vascular changes and with features suggesting
      severe portal hypertension. These results raise the hypothesis that intrahepatic
      vascular changes precipitate the development of HPS, opening new therapeutic
      perspectives for HPS.

PMID- 30292763
TI  - Prevalence and molecular characteristics of methicillin-resistant Staphylococcus
      aureus among nasal carriage strains isolated from emergency department patients
      and healthcare workers in central Taiwan.
AB  - BACKGROUND AND OBJECTIVE: Screening and identification of methicillin-resistant
      Staphylococcus aureus (MRSA) carriage are helpful for controlling MRSA
      dissemination in hospitals. The aim of our study was to determine the prevalence
      of nasal carriages and diversity of MRSA among patients and healthcare workers
      (HCWs) at two regional hospitals in Taiwan. METHODS: Nasal swabs were obtained
      prospectively from 204 patients visiting the emergency department (ED) and 326
      HCWs in two regional hospitals in Changhua, Taiwan, between February 2015 and
      June 2015. All the MRSA isolates were further molecularly characterized. RESULTS:
      Of the 204 participating patients, the nasal carriage rates of S. aureus and MRSA
      were 22.1% and 7.8%, respectively. For HCWs, the S. aureus and MRSA carriage
      rates were 26.1% and 6.1%, respectively. There was no statistically significant
      difference in MRSA carriage rate between patients and HCWs (P = 0.447). Patients
      receiving hemodialysis were significantly associated with MRSA colonization (P =
      0.012). The leading three sequence types (ST) were ST59 (16, 44.4%), ST45 (11,
      30.6%), and ST239 (3, 8.3%) for all 36 MRSA isolates. ST59/SCCmec IV/t437/PVL
      negative and ST45/SCCmec V/t1081/PVL-negative were the predominant clones among
      HCWs (30%) and participating patients (19%), respectively. CONCLUSION: Overall, a
      substantial proportion of patients visiting the ED and HCWs harbored CA-MRSA,
      mostly ST59 strains, in their nares. It is noteworthy that MRSA ST45 strains
      supplanted ST239 as the second leading nasal MRSA colonization strain in our
      study.

PMID- 30292764
TI  - Long-term Object Discrimination at Several Viewpoints Develops Neural Substrates
      of View-invariant Object Recognition in Inferotemporal Cortex.
AB  - Object recognition requires differentiation across different objects and
      generalization across views of the same object. We previously demonstrated that
      discrimination of object images at several views without any possibility of
      association was enough to achieve object recognition within a certain range of
      viewing angles and confirmed the response tolerance of monkey inferotemporal
      cells within a similar range of viewing angles. However, neither behavioral
      object recognition nor electrophysiological response tolerance was complete
      across views. In the present study, we extended such learning past performance
      saturation and recorded neuronal activity during the further learning period.
      When monkeys were trained to discriminate objects at several views, we found that
      they could discriminate the trained objects regardless of the eventual change in
      viewing angle, and confirmed a response tolerance at the population level over a
      large viewing angle range covering all the viewpoints experienced. At the cell
      population level, such overtraining leads to significantly higher neural response
      similarity for views of the same objects than for views of different objects
      regardless of the extent of viewing angle separation. These results suggest a
      possible method of view-invariant object recognition development.

PMID- 30292765
TI  - Testing the Central Gain Model: Loudness Growth Correlates with Central Auditory
      Gain Enhancement in a Rodent Model of Hyperacusis.
AB  - The central gain model of hyperacusis proposes that loss of auditory input can
      result in maladaptive neuronal gain increases in the central auditory system,
      leading to the over-amplification of sound-evoked activity and excessive loudness
      perception. Despite the attractiveness of this model, and supporting evidence for
      it, a critical test of the central gain theory requires that changes in sound
      evoked activity be explicitly linked to perceptual alterations of loudness. Here
      we combined an operant conditioning task that uses a subject's reaction time to
      auditory stimuli to produce reliable measures of loudness growth with chronic
      electrophysiological recordings from the auditory cortex and inferior colliculus
      of awake, behaviorally-phenotyped animals. In this manner, we could directly
      correlate daily assessments of loudness perception with neurophysiological
      measures of sound encoding within the same animal. We validated this novel
      psychophysical-electrophysiological paradigm with a salicylate-induced model of
      hearing loss and hyperacusis, as high doses of sodium salicylate reliably induce
      temporary hearing loss, neural hyperactivity, and auditory perceptual disruptions
      like tinnitus and hyperacusis. Salicylate induced parallel changes to loudness
      growth and evoked response-intensity functions consistent with temporary hearing
      loss and hyperacusis. Most importantly, we found that salicylate-mediated changes
      in loudness growth and sound-evoked activity were correlated within individual
      animals. These results provide strong support for the central gain model of
      hyperacusis and demonstrate the utility of using an experimental design that
      allows for within-subject comparison of behavioral and electrophysiological
      measures, thereby making inter-subject variability a strength rather than a
      limitation.

PMID- 30292766
TI  - Exploiting Drug-Apolipoprotein E Gene Interactions in Hypertension to Preserve
      Cognitive Function: The 3-City Cohort Study.
AB  - OBJECTIVES: The objective was to test the hypothesis that antihypertensive drugs
      have a differential effect on cognition in carriers and noncarriers of the
      apolipoprotein epsilon4 (APOE4) polymorphism. DESIGN: Prospective population
      based cohort, France. SETTING AND PARTICIPANTS: A total of 3359 persons using
      antihypertensive drugs (median age 74 years, 62% women) were serially assessed up
      to 10 years follow-up. MEASURES: Exposure to antihypertensive drug use was
      established in the first 2 years. Cognitive function was assessed at baseline, 2,
      4, 7, and 10 years with a validated test battery covering global cognition,
      verbal fluency, immediate visual recognition memory, processing speed, and
      executive function. Clinically significant change in cognitive function was
      determined using reliable change indices represented as z scores and analyzed
      with linear mixed-models. RESULTS: From 3359 persons exposed to antihypertensive
      drugs, 653 were APOE4 carriers (5.1% homozygous, 94.9% heterozygous) and median
      follow-up was 5.2 years (interquartile range 3.7-8.0). In APOE4 carriers,
      improved general cognitive function over time was associated with exposure to
      angiotensin converting enzyme inhibitors [beta = .14; 95% confidence interval
      (CI) .06-.23, P = .001] and angiotensin receptor blockers (beta = .11; 95% CI .02
      .21, P = .019). Improved verbal fluency was associated with angiotensin
      converting enzyme inhibitors (beta = .11; 95% CI .03-.20, P = .012). CONCLUSIONS:
      Renin-angiotensin-system blockade was associated with improved general cognitive
      function in APOE4 carriers. Findings did not support renin-angiotensin-system
      drugs' lipophilicity or ability to cross the blood-brain barrier as potential
      mechanisms. The findings have implications for selecting the optimal
      antihypertensive drug in older populations at risk of cognitive decline and
      dementia.

PMID- 30292767
TI  - The prevalence of low serum free testosterone and the short-term effect of anti
      retroviral therapy in male Japanese treatment-naive HIV patients.
AB  - OBJECTIVES: The prevalence of hypogonadism in HIV patients is still a matter of
      debate. Today, serum free testosterone (fTST) is thought to be more important
      than serum testosterone in the diagnosis of hypogonadism in patients with HIV.
      This study aimed to determine the prevalence of low fTST levels and the effects
      of anti-retroviral therapy (ART) on fTST levels in treatment-naive male Japanese
      patients with HIV. METHODS: Patients who visited Teikyo University Hospital,
      Japan between 2010 and 2016 were enrolled. Patients' fTST levels were evaluated
      twice with a radioimmunoassay in the morning, at the onset of ART and one year
      later. Clinical factors were also reviewed. The patients were divided into two
      groups ('hypogonadism' and 'normal') based on Japanese criteria. To determine
      factors related to low fTST in treatment-naive patients, the Mann-Whitney U test
      and a multiple-regression analysis were used. Changes in fTST levels after ART
      initiation were evaluated with a paired t-test. RESULTS: Data from 25 patients
      were collected. Their median age was 36.0 years, and the median fTST level was
      8.00 pg/ml in the treatment-naive state. Thirteen patients (52%) were in the
      hypogonadism group. Low levels of fibroblast growth factor 23 were significantly
      related to low fTST levels. After the start of ART, fTST levels increased
      significantly (median 8.00 interquartile range [6.40-9.70] to 9.60 [7.60-13.10]
      pg/ml, p = 0.0081). CONCLUSIONS: Subnormal fTST levels occurred frequently among
      the present study patients in treatment-naive settings. Free testosterone levels
      in patients with HIV were significantly increased one year after the start of
      ART.

PMID- 30292768
TI  - Characterization of CTX-M type ESBL-producing Enterobacteriaceae isolated from
      asymptomatic healthy individuals who live in a community of the Okinawa
      prefecture, Japan.
AB  - This study was performed to characterize CTX-M type extended spectrum beta
      lactamase (ESBL)-producing Enterobacteriaceae carriage in asymptomatic health
      individuals, which has not been well investigated, in a community of the Okinawa
      prefecture, Japan. Fecal samples were voluntary collected from asymptomatic
      healthy individuals who were going to take a routine medical checkup. The
      collected fecal samples were inoculated on MacConkey agar supplemented with 2
      MUg/ml of cefotaxime and incubated at 37  degrees C. Randomly selected three
      lactose-fermented colonies per each sample were analyzed. Genetic relatedness
      among the CTX-M type ESBL-producing Enterobacteriaceae isolates were performed by
      pulsed-field gel electrophoresis (PFGE) after confirmation of ESBL phenotype and
      determination of bacterial species. Location of blaCTX-M was confirmed by S1
      PFGE, I-CeuI-PFGE and the Southern blotting hybridization. ESBL-producing
      Enterobacteriaceae was isolated from 32 (12.2%) of the collected 263 fecal
      samples, and 96 ESBL-producing Enterobacteriaceae isolates were obtained. CTX-M
      type ESBL-producing Escherichia coli B2 were major (67 isolates, 72.0%) and 40
      (59.7%) of the 67 CTX-M type ESBL -producing E. coli B2 were E. coli B2-ST131.
      Three CTX-M type ESBL-producing E. coli B2-ST131 isolates from asymptomatic
      healthy individuals showed similar PFGE band patterns as five CTX-M type ESBL 
      producing E. coli B2-ST131 isolates from a hospital locates in the same area of
      the target community. Chromosomally-transferred blaCTX-M was observed in 10.0% of
      the examined CTX-M type ESBL-producing Enterobacteriaceae isolates. We report
      current situation CTX-M type ESBL-producing Enterobacteriaceae carriage in
      asymptomatic healthy individuals of the Okinawa prefecture, Japan. In addition,
      our results indicated that worldwide distributed CTX-M type ESBL-producing E.
      coli B2-ST131 has been spread in a community. Therefore monitoring of ESBL
      producing Enterobacteriaceae in healthy individuals is important.

PMID- 30292769
TI  - Exploring microRNA profiles for circadian clock and flowering development
      regulation in Himalayan Rhododendron.
AB  - miRNA is a non-coding, yet crucial entity in remodeling the genetic architecture.
      Rhododendron arboreum of Himalayas grows and even flower under fluctuating
      climate. sRNA from leaves of vegetative and reproductive periods was sequenced to
      elucidate its seasonal associations. Conserved (256) and novel (210) miRNAs and
      their precursors were located based on homology with plant databases and
      transcriptome of the species. 27,139 predicted targets were involved with
      metabolism, reproduction, and response to abiotic stimuli. A comparative analysis
      showed differential expression of 198 miRNAs with season-specific abundance of
      103 miRNAs. Specific isoforms of 11 miRNA families exhibited a temporal
      expression and targeted different genes implying a complex regulation. The
      variable miRNA expression among the tissues of different conditions can be
      associated with the adaptability of the species, which will prove essential for
      further study on miRNAs mediating seasonal response. Moreover, exogenous cues
      also mediate phase transition via networking of flowering pathways and their
      components. In this context, 18 known families and 77 novel miRNAs modulating 117
      genes crucial in circadian entrainment were filtered. A negative correlation was
      obtained between the expression of 18 of these miRNAs and their targets when
      tested through quantitative-PCR. It highlighted the role of miRNA-target pairs in
      perceiving environmental variabilities and monitoring flowering growth.
      Furthermore, a phylogenetic clustering was performed, which supported the lineage
      specific evolution and function of putative miR156 sequence in the species. This
      documentation of genome-wide profiling of miRNA, their targets, and expression
      will enhance the understanding of developmental and climate-tolerance strategies
      in high-altitude trees.

PMID- 30292770
TI  - NO-sGC-cGMP signaling influence the anxiolytic like effect of lithium in mice in
      Light and dark box and elevated pus maze.
AB  - Glutamate is an excitatory neurotransmitter implicated in the pathogenesis of
      psychiatric disorders. Glutamate results in the activation of an enzyme called
      glycogen synthase kinase-3 (GSK-3) acting through N-methyl-D-aspartate (NMDA)
      receptors. Impaired expression of GSK-3 affects behavior and neurochemicals level
      in the brain responsible for the pathogenesis of mood disorders. It has been
      reported that lithium acts as an inhibitor of GSK-3 and inhibit the enzyme GSK-3
      in an uncompetitive manner. In the present study, anxiolytic like effect of
      lithium in mice is investigated through light and dark box (LDB) and elevated pus
      maze (EPM). Lithium (50, 100 and 200 mg/kg, i.p.) was administered to the mice to
      determine the anxiety related behavior. Results obtained suggests that the
      administration of lithium (100 mg/kg, i.p.) reversed the anxiety related behavior
      of mice and decreased the levels of glutamate and nitrite as compared to control.
      Glutamate acting through the NMDA receptor has been found to regulate the
      expression of enzyme neuronal nitric oxide synthase (nNOS), which is responsible
      for the release of nitric oxide (NO), suggesting a possible link between NO and
      GSK-3 also. Therefore, to determine the possible interaction with NO, sub
      effective dose of lithium was administered in combination with NO donor i.e. L
      Arginine (50 mg/kg, i.p.), NOS and soluble guanylate cyclase (sGC) inhibitor i.e.
      methylene blue (1 mg/kg, i.p.) and phosphodiesterase inhibitor i.e. sildenafil (1
      mg/kg, i.p.). The results obtained demonstrated that the anxiolytic like effect
      of lithium was abolished by the pretreatment with NO donor and potentiated by the
      pretreatment with NOS inhibitor. Therefore, it is suggested that NO signaling
      pathway influence the anxiolytic like activity of lithium in mice, further
      suggesting the link between the GSK-3 and NO signaling in the regulation of
      anxiety related behavior.

PMID- 30292771
TI  - The decline of whole-body glucose metabolism in ovariectomized rats.
AB  - Age is a major risk factor for developing chronic diseases, including type 2
      diabetes and osteoporosis. Emerging evidences suggest that the disorder of bone
      metabolism in osteoporosis is involved in the pathogenesis of glucose
      intolerance, insulin resistance and type 2 diabetes. However, their etiology and
      relative regulatory factors still remain elusive to clinicians and researchers.
      In this study, rats were divided into two groups: normal sham surgery control and
      ovariectomized (OVX) groups. We evaluated the global bone parameters, glucose
      metabolism, protein and gene expressions in both skeletal muscle and adipocytes.
      The present findings showed that the bone mineral density (BMD) and compression
      load of bone were markedly reduced in OVX rats as revealed by micro-CT, dual
      energy X-ray absorptiometry and bone biomechanics analysis. Besides, plasma
      estrogen, total alkaline phosphatase (TALP) and osteocalcin levels were
      significantly decreased in the OVX rats, but body weight, fat mass and plasma
      tartrate-resistant acid phosphatase (TRAP) and chemerin levels were significantly
      increased in the OVX rats. More interestingly, we found that p-AKT, p-P38MAPK,
      glucose transporter 4 (GLUT4) and peroxisome proliferator-activated receptor
      gamma coactivator 1 alpha (PGC-1alpha) contents as well as GLUT4 and PGC-1alpha
      mRNA expression were significantly decreased in skeletal muscle and adipocytes of
      OVX rats. In conclusion, our results indicated that whole-body glucose metabolism
      and glucose intolerance in OVX rats was degressive, suggesting there was a novel
      link between osteoporosis and whole body glucose homeostasis, which are
      controlled by the P38MAPK/PGC-1alpha/GLUT4 signaling pathway.

PMID- 30292772
TI  - Patterns of healthy lifestyle behaviours in older adults: Findings from the
      Chilean National Health Survey 2009-2010.
AB  - The purpose of this study was to investigate healthy lifestyle behaviours across
      age categories in the older population in Chile. Data from 1390 older adults
      (>=60 years), in the 2009-2010 Chilean National Health Survey were analyzed. We
      derived the following age categories: 60-65, 66-70, 71-75, 76-80 and >80 years.
      The associations between age and compliance with healthy lifestyle behaviours
      (smoking, sitting time, physical activity, sleep duration and intake of salt,
      alcohol, fruit and vegetables) were investigated using logistic regression. The
      probability of meeting the guidelines for alcohol intake (OR trend: 1.35 [95% CI:
      1.11; 1.64], p = 0.001) and smoking (OR trend: 1.23 [95% CI: 1.13; 1.33], p <
      0.0001) increased with age, whereas spending <4 h per day sitting time or
      engaging in at least 150 min of physical activity per week or sleep on average
      between 7 and 9 h per day were less likely to be met with increasing age (OR
      trend: 0.77 [95% CI: 0.71; 0.83], p < 0.000; OR trend: 0.73 [95% CI: 0.67; 0.79],
      p < 0.0001, and OR trend: 0.89 [95% CI: 0.82; 0.96], p = 0.002, respectively). No
      significant trend across age categories was observed for fruit and vegetables,
      and salt intake. The probability of meeting at least 3 out of 7 healthy lifestyle
      behaviours across the age categories was also lower in older age categories
      compared to those aged 60 to 65 years. Overall, in older adults the probability
      of having the healthy lifestyle behaviours of physical activity, sitting time and
      sleeping behaviours was low but not for smoking or alcohol consumption. With an
      increasingly ageing population, these findings could inform stakeholders on which
      lifestyle behaviours could be targeted in the older adults and therefore which
      interventions should take place to promote healthy ageing.

PMID- 30292773
TI  - Pragmatic Trial to Evaluate the Effect of a Promotora Telephone Intervention on
      the Duration of Breastfeeding.
AB  - OBJECTIVE: To evaluate the effectiveness of a telephone intervention delivered by
      promotoras (lay health care workers) to increase the duration of exclusive
      breastfeeding (EBF) in Hispanic women at 12 weeks postpartum. Secondary
      objectives were to assess breastfeeding duration (BFD) and to evaluate background
      variables that may be associated with EBF and BFD. DESIGN: Pragmatic trial.
      SETTING: Two obstetric clinics affiliated with a community medical center in
      Southern California. PARTICIPANTS: We recruited 61 participants from the two
      clinics. Participants were 18 to 45 years old and planned to breastfeed their
      infants. Women who showed interest in the study were sequentially divided into an
      intervention (n = 31) or a control group (n = 30). METHODS: The intervention
      consisted of telephone support for breastfeeding provided by certified and
      trained promotoras. RESULTS: Fourteen out of 31 (45%) participants in the
      intervention group continued to practice EBF compared with 4 out of 30 (13%) in
      the control group (odds ratio = 3.39, p = .04). Breastfeeding duration in days
      was significantly longer for the participants in the intervention group (F =1/59
      = 29.88, p < .01). The positive predictors of EBF at 12 weeks after birth were
      prior breastfeeding experience, perceived breastfeeding support, promotora
      telephone support, and higher scores on the acculturation scale. Positive
      predictors of BFD were breastfeeding support, promotora telephone support, and
      higher scores on breastfeeding self-efficacy. A negative predictor was lower
      household income. CONCLUSION: Our results indicate that a telephone support
      intervention delivered by promotoras may increase the rates of EBF by threefold
      at 12 weeks after birth.

PMID- 30292774
TI  - Relationship Between Mindfulness and Posttraumatic Stress in Women Who
      Experienced Stillbirth.
AB  - OBJECTIVE: To explore the potential factors that mediate the relationship between
      mindfulness and symptoms of posttraumatic stress (PTS) in women who experienced
      stillbirth. DESIGN: A cross-sectional analysis of baseline data before women's
      participation in an online mindfulness intervention (i.e., online yoga). SETTING:
      This was a national study, and women participated in their own homes.
      PARTICIPANTS: Women who experienced stillbirth (N = 74) within the past 2 years
      and resided in the United States. METHODS: Women were recruited nationally,
      primarily through social media. Participants (N = 74) completed baseline
      assessments (self-report mental and physical health surveys) via a Web-based
      survey tool. We conducted an exploratory factor analysis of the COPE Inventory
      subscales to reduce the number of variables before entry into a mediation model.
      We then tested the mediation effects of sleep quality, self-esteem, resilience,
      and maladaptive coping on the relationship between mindfulness and PTS symptoms.
      RESULTS: Through the exploratory factor analysis we identified a two-factor
      solution. The first factor included nine subscales that represented adaptive
      coping strategies, and the second factor included five subscales that represented
      maladaptive coping strategies. Results from multiple mediation analysis suggested
      that mindfulness had a significant inverse relationship to PTS symptoms mediated
      by sleep quality. CONCLUSION: Mindfulness practices may have potential benefits
      for grieving women after stillbirth. Evidence-based approaches to improve sleep
      quality also may be important to reduce PTS symptoms in women after stillbirth.

PMID- 30292775
TI  - Implementation of Delayed Cord Clamping in Vigorous Preterm Neonates.
AB  - OBJECTIVE: To adopt evidence-based recommendations to delay cord clamping in
      vigorous preterm neonates. DESIGN: Evidence-based practice change project with
      quantitative data. SETTING/LOCAL PROBLEM: Delayed cord clamping (DCC) was not a
      usual practice at the hospital where this project took place, despite research
      findings that show benefits of DCC for preterm neonates. PARTICIPANTS: Vigorous
      neonates born before 37 weeks completed gestation. INTERVENTION/MEASUREMENT: An
      interprofessional obstetric team of obstetricians and registered nurses
      implemented DCC for up to 1 minute for vigorous preterm neonates. RESULTS: We
      found that Apgar scores at 1 minute (mean [M] = 8.35, standard deviation [SD] =
      .551, n = 31) were statistically significantly higher with DCC than at 1 minute
      with immediate cord clamping (M = 7.16, SD = 1.834, n = 19) at t (20.008) =
      1.197, p = .012. The Apgar scores at 5 minutes (M = 9.00, SD = 0.258, n = 31)
      were statistically significantly higher with DCC than at 5 minutes with immediate
      cord clamping (M = 8.58, SD = .838, n = 19) at t (20.116) = 2.130, p = 0.046.
      CONCLUSION: Delayed cord clamping was adopted as a usual clinical practice, and
      implementation of this practice in vigorous preterm neonates increased their
      Apgar scores. The obstetric team's awareness, experience, and professional
      perspectives about DCC improved.

PMID- 30292776
TI  - Using Mobile Technologies to Improve Women's Health.

PMID- 30292777
TI  - The role of genetics in stress effects on health and addiction.
AB  - Advances in stress research have yielded new insights into how stress exposure,
      in combination with genetics, can contribute to poor health outcomes. We review
      these topics with a special emphasis on early life stress and vulnerability to
      addiction. The direct effects of stress and our compensatory responses can modify
      our physiology and behavior during future stress episodes. These consequences can
      influence health, including an increased propensity for addiction. The relation
      between stress and health is not uniform across individuals. Some people succumb
      to stress-related disorders while others are resilient. Specific genetic
      polymorphisms affect how an individual appraises and responds to stress,
      potentially mediating the impact of stress on health. These genetic
      vulnerabilities can influence responses to the external environment, shape
      motivated behavior, and have an impact on health throughout life.

PMID- 30292778
TI  - Liposomal bupivacaine reduces narcotic use and time to flatus in a retrospective
      cohort of patients who underwent laparotomy.
AB  - INTRODUCTION: Sustained release liposomal bupivacaine (LB) is a new pain control
      option that can reduce opioid use after laparotomy, which is known to prolong
      ileus, length of stay. METHODS: Sixty-one consecutive patients undergoing
      laparotomy were treated with a standardized multi-modal therapy (MMT) consisting
      of IV tylenol, toradol, and morphine/dilaudid PCA. Thirty-one of those patients
      were additionally treated with LB infiltrated during fascial closure. Endpoints
      were opioid use, time to flatus, length of stay, and complications. RESULTS:
      Overall opioid use for 72 h was 78 mg of morphine for the MMT + LB group and 112
      mg in the MMT control group (p = 0.04). During 0-24 h s PCA use was similar.
      However, during 24-48 h PCA use was decreased by 46% in the MMT + LB group (p =
      0.038), and decreased by 55% during the 48-72 h period (p = 0.019). Time to
      flatus was decreased by 1.0 days in the MMT + LB group (p = 0.005). CONCLUSION:
      Use of LB in laparotomy patients decreases opioid use, time to flatus, and should
      be considered as a component of post-operative pain control.

PMID- 30292779
TI  - Views of the importance of psychiatric genetic research by potential volunteers
      from stakeholder groups.
AB  - Few studies have explored potential volunteers' attitudes toward genetic
      research. To address this gap in the literature, we developed an empirical
      project to document views held by individuals who may wish to enroll in genetic
      studies involving mental disorders. People living with mental illness, family
      members of people with mental illness, and community comparison volunteers were
      queried regarding their views on the importance of genetic research generally, in
      comparison with medical research, and in relation to 12 health conditions
      categorized in four types. T-tests and univariate and multivariate analysis of
      variance were used as appropriate. Participants expressed support for the
      importance of genetic research (mean = 9.43, scale = 1-10) and endorsed genetic
      research more highly compared with non-genetic medical research (mean = 9.43 vs.
      8.69, P value = <0.001). The most highly endorsed genetic research was for
      cognitive disorders, followed by mental illness disorders, physical illness
      disorders, and addiction disorders (means = 8.88, 8.26, 8.16 and 7.55,
      respectively, P value = <0.001). Overall, this study provides evidence of strong
      endorsement of genetic research over non-genetic research by potential
      volunteers.

PMID- 30292780
TI  - Free thyroxine and thyroid-stimulating hormone in severe mental disorders: A
      naturalistic study with focus on antipsychotic medication.
AB  - BACKGROUND: Disturbances in thyroid function have been associated with use of
      psychotropic drugs, including antipsychotics. Still, the thyroid function in
      relation to commonly prescribed antipsychotic drugs and polypharmacy is not fully
      known. We investigated thyroid function associated with use of antipsychotics in
      patients with psychotic disorders compared with healthy controls. METHODS: We
      included 1345 patients and 989 healthy controls from the Thematically Organized
      Psychosis (TOP) study, recruiting participants between 18 and 65 years of age in
      the Oslo-area. All patients underwent a thorough clinical investigation and
      assessment of medication data. Thyroid function was determined from plasma levels
      of free thyroxin (fT4) and thyroid-stimulating hormone (TSH). Multiple linear
      regression analyses were performed to evaluate the association between thyroid
      parameters and use of antipsychotics, and monotherapy users of olanzapine,
      quetiapine, aripiprazole or risperidone (N = 473) were investigated separately.
      RESULTS: We found lower levels of fT4 (median 13.70 vs 14.00, p < 0.001) in
      patients compared to healthy controls, and a prevalence of 12.9% of previously
      undiagnosed deviant thyroid states in the patient group. Lower fT4 levels was
      associated with use of antipsychotics in general (p = 0.001), and quetiapine (p =
      0.003) and olanzapine (p = 0.018) in particular, while the associations with TSH
      were non-significant. Using antipsychotics in combination with other psychotropic
      drugs, and with antidepressants in particular, was associated with lower fT4
      level (p < 0.001) than use of antipsychotics alone. CONCLUSIONS: Our findings
      indicate an association between use of antipsychotics and lower fT4. Clinicians
      should be aware that patients using quetiapine, olanzapine or antipsychotics in
      psychotropic polypharmacy are especially at risk.

PMID- 30292781
TI  - Use of disposable blade for harvesting epidermal skin graft.

PMID- 30292782
TI  - Missed Hepatitis B Birth Dose Vaccine Is a Risk Factor for Incomplete Vaccination
      at 18 and 24 Months.
AB  - OBJECTIVES: To determine whether missing the HepB birth dose vaccine is a risk
      factor for incomplete vaccination later in childhood. METHODS: This was a
      retrospective cohort study of infants born over one year at an academic medical
      center. The "not vaccinated at birth" group consisted of all infants who did not
      receive the HepB birth dose vaccine by seven days of life, while the "vaccinated
      at birth" group included infants who did receive the birth dose. The primary
      outcome was vaccination status at 18 months of age, determined from the state
      vaccination registry. RESULTS: Infants "not vaccinated at birth" had lower
      vaccination rates. At 18 months, 44% of the "vaccinated at birth" group received
      all recommended vaccines, compared with 23% of the "not vaccinated at birth"
      group (p<0.001); at 24 months, rates were 65% and 45%, respectively (p<0.001).
      Over 80% of the variability in vaccination completions were related to a single
      latent variable, which is most likely vaccine hesitancy/refusal. CONCLUSIONS:
      Infants who miss the HepB birth dose vaccine are at risk for under-immunization
      by 18 and 24 months of age. This suggests that parents likely form opinions about
      vaccines long before the birth of their child; therefore, efforts to influence
      attitudes must begin earlier.

PMID- 30292783
TI  - Similar distraction, but differential suppression, for faces and non-face
      objects: Evidence from behaviour and event-related potentials.
AB  - In everyday life we constantly experience distractions. Some distractors might be
      more distracting than others, for example the human face, which has been shown to
      be very efficient in attracting attention. Here, we employed the irrelevant
      distractor paradigm (Forster & Lavie, 2016) to measure behavioural and neural
      distraction by completely irrelevant faces or non-faces (cars), while
      participants performed a letter search task that was more (high-load) or less
      (low-load) demanding. Under low load conditions, faces and cars equally slowed
      responses on trials with distractors as compared to those without. In high load
      conditions, neither faces nor cars were distracting. However, event-related
      potentials revealed larger face-sensitive N170 responses to faces than cars under
      both load conditions, suggesting that early face-specific processing is present
      even under high load. A subsequent Pd modulation between 200 and 300 ms
      contralateral to the distractor position, which has been linked to the active top
      down suppression of lateral distractors (Hickey et al., 2009) was stronger for
      faces compared to cars. Overall, the EEG data indicate early face-specific
      processes to irrelevant faces irrespective of attentional load, coupled with
      stronger top-down suppression for faces. Together, these processes might reduce
      the influence of irrelevant face distractors on behavioural performance.

PMID- 30292784
TI  - The importance of precision to updating models of the sensory environment.
AB  - The existence and updating of "sensory beliefs" or internal models can be studied
      using auditory evoked potentials (AEPs) when there is some form of predictable
      pattern in sound. Internal models are proposed to enable predictions about the
      most likely next sound-activation-state leading to small AEPs to standard sounds
      matching model predictions, and larger AEPs to sound that deviate. Internal
      models are precision-weighted with the standard-deviant difference being largest
      when precision is high (variability is low). Here we expose how order-effects
      determine whether a change in variability impacts model-precision estimates.
      Thirty participants heard 3000 t (30 ms standard p = 0.90 and 60 ms deviant p =
      0.10) that either moved from a more precise stimulus onset asymmetry (n = 15,
      first 1000 tones 500 ms +/- 10 ms) to a more variable one (n = 15, subsequent
      2000 tones 500 ms +/- 200 ms) or from variable (first 1000 t) to more precise
      (subsequent 2000 t). AEPs were equivalent between groups for the first 1000 tones
      but differed dramatically in the face of timing changes. Where timing precision
      decreased, the standard-deviant difference was impervious to the change but where
      precision increased, the standard-deviant difference increased dramatically after
      the timing change signalling a transient increase in model precision that
      subsided over the final 1000 tones. The results support contemporary models
      proposing that updates to an active internal model will be a function of the
      quality of the evidence upon which it has been built and the information value of
      subsequent errors in improving the predictive success of the active model.

PMID- 30292785
TI  - The Neurobiology of Reduced Autobiographical Memory Specificity.
AB  - There has been a recent growth in investigations into the neural mechanisms
      underlying the problems recalling specific autobiographical events that are a
      core feature of emotional disorders. In this review we provide the first
      synthesis of this literature, taking into account brain as well as cognitive
      mechanisms. We suggest that these problems are driven by idiosyncratic activation
      in areas of the brain associated with assigning salience and self-relevance to
      emotional memories. Other areas associated with inhibiting distraction and
      constructing vivid memory representations are also important. Each of these
      mechanisms may work independently or in concert with one another. Importantly,
      this interaction between mechanisms may differ between diagnostic and demographic
      groups such that similar problems in specificity may be characterised by
      different mechanisms. Given this challenge, neuroimaging may prove useful in
      identifying patient-specific biomarkers for interventions.

PMID- 30292786
TI  - Loss of Tbx3 in murine neural crest reduces enteric glia and causes cleft palate,
      but does not influence heart development or bowel transit.
AB  - Transcription factors that coordinate migration, differentiation or proliferation
      of enteric nervous system (ENS) precursors are not well defined. To identify
      novel transcriptional regulators of ENS development, we performed microarray
      analysis at embryonic day (E) 17.5 and identified many genes that were enriched
      in the ENS compared to other bowel cells. We decided to investigate the T-box
      transcription factor Tbx3, which is prominently expressed in developing and
      mature ENS. Haploinsufficiency for TBX3 causes ulnar-mammary syndrome (UMS) in
      humans, a multi-organ system disorder. TBX3 also regulates several genes known to
      be important for ENS development. To test the hypothesis that Tbx3 is important
      for ENS development or function, we inactivated Tbx3 in all neural crest
      derivatives, including ENS progenitors using Wnt1-Cre and a floxed Tbx3 allele.
      Tbx3 fl/fl; Wnt1-Cre conditional mutant mice die shortly after birth with cleft
      palate and difficulty feeding. The ENS of mutants was well-organized with a
      normal density of enteric neurons and nerve fiber bundles, but small bowel glial
      cell density was reduced. Despite this, bowel motility appeared normal.
      Furthermore, although Tbx3 is expressed in cardiac neural crest, Tbx3 fl/fl; Wnt1
      Cre mice had structurally normal hearts. Thus, loss of Tbx3 within neural crest
      has selective effects on Tbx3-expressing neural crest derivatives.

PMID- 30292787
TI  - TRPV1 modulates morphine self-administration via activation of the CaMKII-CREB
      pathway in the nucleus accumbens.
AB  - Opioid addiction is a growing problem for public health, and opioids have
      correspondingly become more heavily regulated over time. We have previously shown
      that TRPV1 plays a critical role in morphine addiction using a self
      administration paradigm in rats, and the current study evaluates the effects of
      the TRPV1 signaling pathway on morphine self-administration (SA). We found that
      treatment with a selective TRPV1 antagonist, SB366791, significantly decreased
      the morphine SA-induced activation of Ca2+/calmodulin-dependent protein kinase II
      (CaMKII), Akt and the cAMP response element binding protein (CREB) in the nucleus
      accumbens (NAc). In addition, phospho-PKA and phospho-PKC expression levels were
      significantly increased in the NAc of the morphine-SA groups, regardless of
      SB366791 treatment. Finally, local microinjection of SB366791 into the NAc
      significantly suppressed the maintenance of morphine SA. Taken together, our
      findings highlight that TRPV1 plays an important role in morphine addiction,
      likely via activation of the CaMKII-CREB pathway in the NAc.

PMID- 30292788
TI  - Multiscale heterogeneity in filamentous microbes.
AB  - Microbial cells within clonal populations can display different morphologies or
      carry out different tasks. This heterogeneity is beneficial at the population
      level and allows microbes to spread risk or separate incompatible activities.
      Heterogeneity is also evident in filamentous bacteria and fungi, which form
      mycelial networks consisting of interconnected hyphae. Here, heterogeneity is
      observed between clonal mycelial particles, between different zones of colonies,
      between adjacent hyphae and even between adjacent compartments of individual
      hyphae. In this review, we compare this multiscale heterogeneity in filamentous
      bacteria and fungi and discuss the underlying mechanisms. These mechanisms might
      provide targets to improve the exploitability of these organisms as cell
      factories in the biotech sector.

PMID- 30292789
TI  - Evaluation of microbiological screening in a neonatal intensive care unit to
      optimize empiric antibiotic use.

PMID- 30292790
TI  - Highlights of the thirteenth annual scientific meeting of the Society of
      Cardiovascular Computed Tomography.
AB  - The 13th Annual Scientific Meeting of the SCCT, held from July 13 to July 15 in
      Dallas, TX, was attended by 690 attendees from 39 countries, 55 sessions with 140
      speakers, and 18 exhibitors with the abstracts of all scientific posters
      published in the Journal of the Cardiovascular Computed Tomography. This article
      summarizes the many themes and topics of presentation and discussion in this
      meeting, and the many technical advances that are likely to impact future
      clinical practice in cardiac computed tomography and feature in future meetings.

PMID- 30292791
TI  - CGPS: A machine learning-based approach integrating multiple gene set analysis
      tools for better prioritization of biologically relevant pathways.
AB  - Gene set enrichment (GSE) analyses play an important role in the interpretation
      of large-scale transcriptome datasets. Multiple GSE tools can be integrated into
      a single method as obtaining optimal results is challenging due to the plethora
      of GSE tools and their discrepant performances. Several existing ensemble methods
      lead to different scores in sorting pathways as integrated results; furthermore,
      it is difficult for users to choose a single ensemble score to obtain optimal
      final results. Here, we develop an ensemble method using a machine learning
      approach called Combined Gene set analysis incorporating Prioritization and
      Sensitivity (CGPS) that integrates the results provided by nine prominent GSE
      tools into a single ensemble score (R score) to sort pathways as integrated
      results. Moreover, to the best of our knowledge, CGPS is the first GSE ensemble
      method built based on a priori knowledge of pathways and phenotypes. Compared
      with 10 widely used individual methods and five types of ensemble scores from two
      ensemble methods, we demonstrate that sorting pathways based on the R score can
      better prioritize relevant pathways, as established by an evaluation of 120
      simulated datasets and 45 real datasets. Additionally, CGPS is applied to
      expression data involving the drug panobinostat, which is an anticancer treatment
      against multiple myeloma. The results identify cell processes associated with
      cancer, such as the p53 signaling pathway (hsa04115); by contrast, according to
      two ensemble methods (EnrichmentBrowser and EGSEA), this pathway has a rank
      higher than 20, which may cause users to miss the pathway in their analyses. We
      show that this method, which is based on a priori knowledge, can capture valuable
      biological information from numerous types of gene set collections, such as KEGG
      pathways, GO terms, Reactome, and BioCarta. CGPS is publicly available as a
      standalone source code at ftp://ftp.cbi.pku.edu.cn/pub/CGPS_download/cgps
      1.0.0.tar.gz.

PMID- 30292792
TI  - Impact of pretransplant CMV-specific T-cell immune response in the control of CMV
      infection after solid organ transplantation: a prospective cohort study.
AB  - INTRODUCTION: Although solid organ transplant (SOT) recipients with pretransplant
      serology for cytomegalovirus (CMV-R+) are considered at intermediate risk for CMV
      infection post transplantation, CMV infection remains a major cause of morbidity
      in this population. We prospectively characterized whether having pretransplant
      CMV-specific cellular immunity is independently associated with controlling
      infection after transplantation in R + SOT recipients. METHODS: A prospective
      cohort of consecutive R + SOT recipients that received pre-emptive treatment for
      CMV infection was monitored after transplantation and variables were recorded
      during the follow-up. The cytomegalovirus-specific T-cell immune response was
      characterized by intracellular cytokine staining and viral loads determined using
      real-time PCR. RESULTS: One hundred and thirty-five R + SOT recipients were
      included (67 kidney, 64 liver, four liver-kidney). Only one-third of the patients
      (42; 31.85%) had CMV-specific T-cell immunity (CD8+CD69+INF-gamma+ T cells
      >0.25%) before transplantation. Patients with negative pretransplant immunity had
      more CMV infection (49, 52.7% vs. 15, 35.7%; p 0.07) and received more antiviral
      therapy than those with immunity (32, 34.4% vs. 6, 14.3%, p 0.016). Having CMV
      specific immunity was an independent factor for protection from developing
      viraemia >=2000 IU/mL (OR 0.276, 95% CI 0.105-0.725, p < 0.01) and lower
      administration of treatment (OR 0.398, 95% CI 0.175-0.905, p 0.028). Only
      patients with no pretransplant CMV-specific T-cell response were diagnosed with
      CMV-disease (8, 8.6% vs. 0, 0%, p 0.05). DISCUSSION: Our results show that having
      a pretransplant CMV specific T-cell response may be associated with a lower rate
      of CMV viraemia and less antiviral treatment after transplantation; however, more
      prospective studies are needed to confirm these findings.

PMID- 30292793
TI  - Characteristics Associated With High-Impact Pain in People With Temporomandibular
      Disorder: A Cross-Sectional Study.
AB  - High-impact (disabling) pain diminishes the quality of life and increases health
      care costs. The purpose of this study was to identify the variables that
      distinguish between high- and low-impact pain among individuals with painful
      temporomandibular disorder (TMD). Community-dwelling adults (N = 846) with
      chronic TMD completed standardized questionnaires that assessed the following: 1)
      sociodemographic characteristics, 2) psychological distress, 3) clinical pain,
      and 4) experimental pain. We used high-impact pain, classified using the Graded
      Chronic Pain Scale, as the dependent variable in logistic regression modeling to
      evaluate the contribution of variables from each domain. Cross-validated area
      under the receiver operating characteristic curve (AUC) quantified model
      discrimination. One-third of the participants had high-impact pain.
      Sociodemographic variables discriminated weakly between low- and high-impact pain
      (AUC = .61, 95% confidence interval [CI] = 0.57, 0.65), with the exception of
      race. An 18-variable model encompassing all 4 domains had good discrimination
      (AUC = 0.79, 95% CI = 0.75, 0.82), as did a simplified model (sociodemographic
      variables plus catastrophizing, jaw limitation, and number of painful body sites)
      (AUC = 0.79, 95% CI = 0.76, 0.82). Duration of pain, sex, and experimental pain
      testing results were not associated. The characteristics that discriminated most
      effectively between people with low- and high-impact TMD pain included clinical
      pain features and the ability to cope with pain. PERSPECTIVE: This article
      presents the results of a multivariable model designed to discriminate between
      people with high- and low-impact pain in a community-based sample of people with
      painful chronic TMD. The findings emphasize the importance of catastrophizing,
      jaw limitation, and painful body sites associated with pain-related impact.

PMID- 30292794
TI  - Drug delivery to the eye anterior chamber by intraocular lenses: An in vivo
      concentration estimation model.
AB  - Drug loaded intraocular lenses have been proposed as an alternative to the
      conventional post-cataract removal prophylaxis through topical drug
      administration, since the drug or combination of drugs released from the lenses
      are delivered directly to the target site. In this work, a mathematical model to
      estimate the concentration of drug released from such lenses in the eye aqueous
      humor was developed. To attain these estimated concentration profiles, partition
      and effective diffusivity coefficients for the specific lens material were
      obtained from standard in vitro release experiments. The model was validated by
      comparing the predicted aqueous humor concentrations with those obtained in in
      vivo studies where hydrophilic acrylic intraocular lens loaded with an antibiotic
      (moxifloxacin) were implanted in rabbits. Subsequently, other partition and
      effective diffusivity values were determined for levofloxacin, diclofenac and
      ketorolac in the same hydrophilic acrylic and in a second material, a silicone
      hydrogel. Predicted drug concentrations in the aqueous humor allowed an initial
      screening and evaluation of the most promising system for post-cataract removal
      prophylaxis, with the hydrophilic acrylic material presenting promising results,
      especially for moxifloxacin and diclofenac controlled release.

PMID- 30292795
TI  - Bispecific anti-mPDGFRbeta x cotinine scFv-Ckappa-scFv fusion protein and
      cotinine-duocarmycin can form antibody-drug conjugate-like complexes that exert
      cytotoxicity against mPDGFRbeta expressing cells.
AB  - Antibody selection for antibody-drug conjugates (ADCs) has traditionally depended
      on its internalization into the target cell, although ADC efficacy also relies on
      recycling of the receptor-ADC complex, endo-lysosomal trafficking, and subsequent
      linker/antibody proteolysis. In this study, we observed that a bispecific anti
      murine platelet-derived growth factor receptor beta (mPDGFRbeta) x cotinine
      single-chain variable fragment (scFv)-kappa constant region (Ckappa)-scFv fusion
      protein and cotinine-duocarmycin can form an ADC-like complex to induce
      cytotoxicity against mPDGFRbeta expressing cells. Multiple anti-mPDGFRbeta
      antibody candidates can be produced in this bispecific scFv-Ckappa-scFv fusion
      protein format and tested for their ability to deliver cotinine-conjugated
      cytotoxic drugs, thus providing an improved approach for antibody selection in
      ADC development.

PMID- 30292796
TI  - Shedding light on microRNA function via microscopy-based screening.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally modulate
      gene expression and orchestrate a wide range of biological and pathological
      processes. The use of high-throughput screening technologies, in particular
      microscopy-based screenings (also known as high-content screenings), coupled with
      genome-wide libraries for modulation of miRNA levels, allow for comprehensive
      functional analysis of each member of the miRNome in different phenotypic cell
      based assays. The wealth of information obtained from such screenings spans
      across various fields of research, including cancer, cardiovascular, cell
      reprogramming, and infection biology. Here, we provide an overview of the
      rationale for performing screenings using synthetic libraries of miRNA mimics and
      inhibitors, and of the microscopy-based miRNA screenings performed to date.
      Moreover, a list of resources available for such endeavor is provided. Finally,
      we describe a detailed procedure for a case study where microscopy-based
      screening using a library of miRNA mimics was performed to identify miRNAs that
      control infection of epithelial cells by the bacterial pathogen Salmonella. The
      methodologies described here can be easily adapted for screenings addressing
      other biological questions.

PMID- 30292797
TI  - Sensitization Profiles to Hazelnut Allergens across the United States of America.

PMID- 30292798
TI  - Level of competence of primary and secondary school teachers in the management of
      anaphylaxis.

PMID- 30292799
TI  - Lupin: An emerging food allergen in the United States.

PMID- 30292800
TI  - Long-distance seed dispersal affects the resilience of banded vegetation patterns
      in semi-deserts.
AB  - Landscape-scale vegetation stripes (tiger bush) observed on the gentle slopes of
      semi-arid regions are useful indicators of future ecosystem degradation and
      catastrophic shifts towards desert. Mathematical models like the Klausmeier model
      a set of coupled partial differential equations describing vegetation and water
      densities in space and time-are central to understanding their formation and
      development. One assumption made for mathematical simplicity is the local
      dispersal of seeds via a diffusion term. In fact, a large amount of work focuses
      on fitting dispersal 'kernels', probability density functions for seed dispersal
      distance, to empirical data of different species and modes of dispersal. In this
      paper, we address this discrepancy by analysing an extended Klausmeier model that
      includes long-distance seed dispersal via a non-local convolution term in place
      of diffusion, and assessing its effect on the resilience of striped patterns.
      Many authors report a slow uphill migration of stripes; but others report no
      detectable migration speed. We show that long-distance seed dispersal permits the
      formation of patterns with a very slow (possibly undetectable) migration speed,
      and even stationary patterns which could explain the inconsistencies in the
      empirical data. In general, we show that the resilience of patterns to reduced
      rainfall may vary significantly depending on the rate of seed dispersal and the
      width of the dispersal kernel, and compare a selection of ecologically relevant
      kernels to examine the variation in pattern resilience.

PMID- 30292801
TI  - Parameter identification of a model for prostate cancer treated by intermittent
      therapy.
AB  - Adenocarcinoma is the most frequent cancer affecting the prostate walnut-size
      gland in the male reproductive system. Such cancer may have a very slow
      progression or may be associated with a "dark prognosis" when tumor cells are
      spreading very quickly. Prostate cancers have the particular properties to be
      marked by the level of prostate specific antigen (PSA) in blood which allows to
      follow its evolution. At least in its first phase, prostate adenocarcinoma is
      most often hormone-dependent and, consequently, hormone therapy is a possible
      treatment. Since few years, hormone therapy started to be provided intermittently
      for improving patient's quality of life. Today, durations of on- and off
      treatment periods are still chosen empirically, most likely explaining why there
      is no clear benefit from the survival point of view. We therefore developed a
      model for describing the interaction between the tumor environment, the PSA
      produced by hormone-dependent and hormone-independent tumor cells, respectively,
      and the level of androgens. Model parameters were identified using a genetic
      algorithm applied to the PSA time series measured in a few patients who initially
      received prostatectomy and were then treated by intermittent hormone therapy
      (LHRH analogs and anti-androgen). The measured PSA time series is quite correctly
      reproduced by free runs over the whole follow-up. Model parameter values allow
      for distinguishing different types of patient (age and Gleason score) meaning
      that the model can be individualized. We thus showed that the long-term evolution
      of the cancer can be affected by durations of on- and off-treatment periods.

PMID- 30292802
TI  - Prediction of neurological outcomes following the return of spontaneous
      circulation in patients with out-of-hospital cardiac arrest: Retrospective fast
      and-frugal tree analysis.
AB  - AIM: Although various quantitative methods have been developed for predicting
      neurological prognosis in patients with out-of-hospital cardiac arrest (OHCA),
      they are too complex for use in clinical practice. We aimed to develop a simple
      decision rule for predicting neurological outcomes following the return of
      spontaneous circulation (ROSC) in patients with OHCA using fast-and-frugal tree
      (FFT) analysis. METHODS: We performed a retrospective analysis of prospectively
      collected data archived in a multi-centre registry. Good neurological outcomes
      were defined as cerebral performance category (CPC) values of 1 or 2 at 28-day.
      Variables used for FFT analysis included age, sex, witnessed cardiac arrest,
      bystander cardiopulmonary resuscitation, initial shockable rhythm, prehospital
      defibrillation, prehospital ROSC, no flow time, low flow time, cause of arrest
      (cardiac or non-cardiac), pupillary light reflex, and Glasgow Coma Scale score
      after ROSC. RESULTS: Among the 456 patients enrolled, 86 (18.9%) experienced good
      neurological outcomes. Prehospital ROSC (true = good), prompt or sluggish light
      reflex response after ROSC (true = good), and presumed cardiac cause (true =
      good, false = poor) were selected as nodes for the decision tree. Sensitivity,
      specificity, positive predictive value, and negative predictive value of the
      decision tree for predicting good neurological outcomes were 100% (42/42), 64.0%
      (119/186), 38.5% (42/109), and 100% (119/119) in the training set and 95.5%
      (42/44), 57.6% (106/184), 35.0% (42/120), and 98.1% (106/108) in the test set,
      respectively. CONCLUSION: A simple decision rule developed via FFT analysis can
      aid clinicians in predicting neurological outcomes following ROSC in patients
      with OHCA.

PMID- 30292803
TI  - Global resuscitation alliance consensus recommendations for developing emergency
      care systems: Reducing perinatal mortality.
AB  - Perinatal and neonatal deaths account for an increasing proportion of deaths
      under 5 years old. We present essential elements to reduce perinatal mortality,
      barriers to establishing these elements, and the role of developing emergency
      care systems. Essential elements for prompt perinatal and postnatal care are
      categorised based on care-seeking behaviours, access to a primary care facility
      and for the severely ill, access to advanced neonatal care. The role of emergency
      care systems is key to overcoming obstacles currently faced in countries with
      high perinatal and neonatal mortality rates.

PMID- 30292804
TI  - Identification of an anti-lipopolysaccharide factor AV-R isoform (LvALF AV-R)
      related to Vp_PirAB-like toxin resistance in Litopenaeus vannamei.
AB  - Acute hepatopancreatic necrosis disease (AHPND) is a shrimp farming disease,
      caused by the pathogenic Vibrio parahaemolyticus carrying a plasmid encoding
      Vp_PirAB-like toxins. Formalin-killed cells of V. parahaemolyticus AHPND-causing
      strain D6 (FKC-VpD6) were used to select Vp_PirAB-like toxin-resistant
      Litopenaeus vannamei by oral administration. Stomach and hepatopancreas tissues
      of shrimps that survived for one week were subjected to RNA sequencing.
      Differentially expressed genes (DEGs) between surviving shrimp, AHPND-infected
      shrimp, and normal shrimp were identified. The expressions of 10 DEGs were
      validated by qPCR. Only one gene (a gene homologous to L. vannamei anti
      lipopolysaccharide factor AV-R isoform (LvALF AV-R)) was expressed significantly
      more strongly in the hepatopancreas of surviving shrimp than in the other groups.
      Significantly higher expression of LvALF AV-R was also observed in shrimp that
      survived two other trials of FKC-VpD6 selection. Recombinant ALF AV-R bound to
      LPS, PGN, Gram-negative bacteria, and some Gram-positive bacteria in ELISAs. ALF
      AV-R recombinant protein did not interact with native Vp_PirAB-like toxin in an
      ELISA or a Far-Western blot. For L. vannamei orally fed ALF AV-R protein for 3
      days, the survival rate following challenge with VpD6-immersion was not
      significantly different from that of shrimp fed two control diets. These results
      suggest that LvALF AV-R expression was induced in the hepatopancreas of shrimp in
      response to the presence of Vp_PirAB-like toxin, although other factors might
      also be involved in the resistance mechanism.

PMID- 30292805
TI  - Thymosins participate in antibacterial immunity of kuruma shrimp, Marsupenaeus
      japonicus.
AB  - Thymosins beta are actin-binding proteins that play a variety of different
      functions in inflammatory responses, wound healing, cell migration, angiogenesis,
      and stem cell recruitment and differentiation. In crayfish, thymosins participate
      in antiviral immunology. However, the roles of thymosin during bacterial
      infection in shrimp remain unclear. In the present study, four thymosins were
      identified from kuruma shrimp, Marsupenaeus japonicus, and named as Mjthymosin2,
      Mjthymosin3, Mjthymosin4, and Mjthymosin5 according the number of their thymosin
      beta actin-binding motifs. Mjthymosin3 was selected for further study because its
      expression level was the highest in hemocytes. Expression analysis showed that
      Mjthymosin3 was upregulated in hemocytes after challenged by Vibrio anguillarum
      or Staphylococcus aureus. The recombinant Mjthymosin3 protein could inhibit the
      growth of certain bacteria in an in vitro antibacterial test. Mjthymosins could
      facilitate external bacterial clearance in shrimp, and were beneficial to shrimp
      survival post V. anguillarum or S. aureus infection. The results suggested that
      Mjthymosins played important roles in the antibacterial immune response of kuruma
      shrimp.

PMID- 30292806
TI  - Expression and purification of a new lectin from mussel Mytilus trossulus.
AB  - The gene of mtl from the mussel Mytilus trossulus was cloned into pET-40b(+)
      expression vector. After expression in E. coli using designed MX-medium an
      instable soluble form of MTL was obtained. The developed isolation method of the
      recombinant protein in "semi-denatured" conditions allowed obtaining an active
      soluble form of the homogenous lectin from the mussel M. trossulus (r-MTL). Both
      of the lectins had similar antigenic and spatial structures.

PMID- 30292807
TI  - High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in
      Pichia pastoris and bioactivity assays in vivo.
AB  - Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria
      nigriventer can be prepared by reversed-phase high-performance liquid
      chromatography (HPLC) fractionation of PhTx4, but this is difficult and
      represents an obstacle preventing analyses of its insecticidal activity against
      agricultural insect pests. Herein, we performed secretory expression of
      recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened
      transformants using enzyme-linked immunosorbent assay (ELISA). In flasks, ~5 mg/l
      rTx4(6-1) was expressed as a secreted protein following induction with methanol,
      and this was increased to 45 mg/l rTx4(6-1) in a fed-batch reactor. Approximately
      4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture
      supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by
      carboxymethyl (CM) sepharose ion-exchange chromatography. Purified rTx4(6-1) was
      determined by mass spectrometry (MS) analysis, revealing a molecular weight (MW)
      of 7660.5 Da, larger than the expected size due to O-linked glycosylation. Insect
      bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori
      Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal
      contraction, and mouth movement syndrome, with a half lethal dose at 12 h post
      injection of ~4.5-8.5 MUg/g body weight. Dietary toxicity was not observed in
      silkworm larvae.

PMID- 30292808
TI  - Alterations in Resting-State Networks Following In Utero Selective Serotonin
      Reuptake Inhibitor Exposure in the Neonatal Brain.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly used to
      treat depression during pregnancy. SSRIs cross the placenta, inhibit serotonin
      reuptake, and thereby are thought to alter central fetal serotonin signaling.
      Both prenatal maternal mood disturbances and in utero SSRI exposure have been
      associated with altered fetal and infant behavior. Resting-state functional
      magnetic resonance imaging has identified resting-state networks (RSNs) in
      newborns, reflecting functional capacity of auditory and visual networks and
      providing opportunities to examine early experiences effects on neurodevelopment.
      We sought to examine the effect of in utero SSRI exposure on neonatal RSN
      functional organization. We hypothesized that prenatal SSRI exposure would be
      associated with alterations in neonatal RSNs compared with healthy control
      infants and infants exposed to mothers with depression. METHODS: Clinician-rated
      Hamilton Depression Rating Scale and self-reported Pregnancy Experiences Scale
      were completed during the third trimester. Control (n = 17), maternal depression
      exposed (Hamilton Depression Rating Scale >=8 without SSRI exposure, n = 16), and
      SSRI-exposed (n = 20) 6-day-old neonates underwent resting-state functional
      magnetic resonance imaging. Independent component analysis was used as a data
      driven approach to extract 22 RSNs. RESULTS: SSRI-exposed neonates had higher
      connectivity in a putative auditory RSN compared with depressed-only (p = .01)
      and control (p = .02) infants (corrected for multiple comparisons), controlling
      for sex, age at the magnetic resonance imaging, and Pregnancy Experiences Scale
      score. CONCLUSIONS: Hyperconnectivity in auditory RSN in neonates with in utero
      SSRI exposure relative to neonates of depressed but not pharmacologically treated
      mothers and control infants may offer an insight into the functional organization
      origins of shifts in language perception and altered language development,
      previously reported in infants and children with prenatal SSRI exposure.

PMID- 30292809
TI  - Preschool Executive Function Predicts Childhood Resting-State Functional
      Connectivity and Attention-Deficit/Hyperactivity Disorder and Depression.
AB  - BACKGROUND: Measures of executive function (EF), such as the Behavior Rating
      Inventory of Executive Function, distinguish children with attention
      deficit/hyperactivity disorder (ADHD) from control subjects, but less work has
      examined relationships to depression or brain network organization. This study
      examined whether early childhood EF predicted new onset or worsening of ADHD
      and/or depression and examined how early childhood EF related to functional
      connectivity of brain networks at school age. METHODS: Participants included 247
      children who were enrolled at 3 to 6 years of age from a prospective study of
      emotion development. The Behavior Rating Inventory of Executive Function Global
      Executive Composite score was used as the measure of EF in early childhood to
      predict ADHD and depression diagnoses and symptoms across school age. Resting
      state functional magnetic resonance imaging network analyses examined global
      efficiency in the frontoparietal, cingulo-opercular, salience, and default mode
      networks and six "hub" seed regions selected to examine between-network
      connectivity. RESULTS: Early childhood EF predicted new onset and worsening of
      ADHD and depression symptoms across school age. Greater EF deficits in preschool
      predicted increased global efficiency in the salience network and altered
      connectivity with four regions for the dorsal anterior cingulate cortex hub and
      one region with the insula hub at school age. This altered connectivity was
      related to increasing ADHD and depression symptoms. CONCLUSIONS: Early executive
      deficits may be an early common liability for risk of developing ADHD and/or
      depression and were associated with altered functional connectivity in networks
      and hub regions relevant to executive processes. Future work could help clarify
      whether specific EF deficits are implicated in the development of both disorders.

PMID- 30292810
TI  - Post rapid freezing growth of Antarctic strain of Heterococcus sp. monitored by
      cell viability and chlorophyll fluorescence.
AB  - The soil microalgae of the genus Heterococcus are found in cold environments and
      have been reported for the terrestrial ecosystems of several Sub-Antarctic and
      Antarctic Islands. This study focused on resistance of Heterococcus sp. to sub
      zero temperature. Heterococcus sp. was isolated from soil samples from James Ross
      Island, Antarctica. Culture of Heterococcus sp. grown in liquid medium were used
      to study ribitol effects at sub-zero temperatures on the species resistance to
      rapid freezing (RF, immersion of a sample into liquid nitrogen) and consequent
      cultivation on agar. Before the experiment, Heterococcus sp. was cultured in
      liquid medium for 11 months and then treated in ribitol concentrations of 32 or
      50 mM for 2 h. Then, 1 ml samples were frozen to -196  degrees C in liquid
      nitrogen (day 0) and inoculated on BBM agar after thawing. Number of living and
      dead cells was evaluated and the cell viability (Pnu) was calculated repeatedly
      using the optical microscopy approach. The addition of ribitol caused a noticable
      increase in Pnu on days 9, 12, 14 (with a Pnu of 25-45% in ribitol-treated
      samples compared to 10% in the untreated control). In the following period (d 16
      19), the positive effect of ribitol on Pnu was less pronounced but still
      statistically significant. To evaluate the negative effects of RF on chlorophyll
      fluorescence parameters, the potential yield of photochemical reactions in PS II
      (FV/FM), and the effective quantum yield of photochemical reactions in PS II
      (FPSII) were measured immediately before and after RF. Consequently, FV/FM and
      FPSII of agar inoculates were measured repeatedly for 30 d cultivation in 3 d
      interval. Both the 32 and the 50 mM addition of ribitol caused earlier detection
      of the parameters (d 16) compared to the control measurements (d 23) as well as
      reaching the maximum values of the chlorophyll fluorescence parameters earlier (d
      23 in ribitol-treated samples compared to d 25 in control samples). Heterococcus
      sp. proved to be a species resistant to rapid freezing. The ability may help the
      species to survive in harsh Antarctic environments typified by rapid fluctuations
      in temperature that may bring a rapid freezing of the alga.

PMID- 30292811
TI  - Cryopreservation of human umbilical vein and porcine corneal endothelial cell
      monolayers.
AB  - Cryopreservation of endothelium is one of the major challenges in the
      cryopreservation of complex tissues. Human umbilical vein endothelial cells
      (HUVECs) in suspension are available commercially and recently their post-thaw
      cell membrane integrity was significantly improved by cryopreservation in 5%
      dimethyl sulfoxide (Me2SO) and 6% hydroxyethyl starch (HES). However,
      cryopreservation of cells in monolayers has been elusive. The exact mechanisms of
      damage during cell monolayer cryopreservation are still under investigation.
      Here, we show that a combination of different factors contribute to significant
      progress in cryopreservation of endothelial monolayers. The addition of 2%
      chondroitin sulfate to 5% Me2SO and 6% HES and cooling at 0.2 or 1  degrees C/min
      led to high membrane integrity (97.3 +/- 3.2%) immediately after thaw when HUVECs
      were cultured on a substrate with a coefficient of thermal expansion similar to
      that of ice. The optimized cryopreservation protocol was applied to monolayers of
      primary porcine corneal endothelial cells, and resulted in high post-thaw
      viability (95.9 +/- 3.7% membrane integrity) with metabolic activity 12 h post
      thaw comparable to unfrozen control.

PMID- 30292812
TI  - Hypothermic pulsatile perfusion of human pancreas: Preliminary technical
      feasibility study based on histology.
AB  - BACKGROUND: There are currently two approaches to hypothermic preservation for
      most solid organs: static or dynamic. Cold storage is the main method used for
      static storage (SS), while hypothermic pulsatile perfusion (HPP) and other
      machine perfusion-based methods, such as normothermic machine perfusion and
      oxygen persufflation, are the methods used for dynamic preservation. HPP is
      currently approved for kidney transplantation. METHODS: We evaluated, for the
      first time, the feasibility of HPP on 11 human pancreases contraindicated for
      clinical transplantation because of advanced age and/or history of severe
      alcoholism and/or abnormal laboratory tests. Two pancreases were used as SS
      controls, pancreas splitting was performed on 2 other pancreases for SS and HPP
      and 7 pancreases were tested for HPP. HPP preservation lasted 24 h at 25 mmHg.
      Resistance index was continuously monitored and pancreas and duodenum histology
      was evaluated every 6 h. RESULTS: The main finding was the complete absence of
      edema of the pancreas and duodenum at all time-points during HPP. Insulin,
      glucagon and somatostatin staining was normal. Resistance index decreased during
      the first 12 h and remained stable thereafter. CONCLUSION: 24 h hypothermic
      pulsatile perfusion of marginal human pancreas-duodenum organs was feasible with
      no deleterious parenchymal effect. These observations encourage us to further
      develop this technique and evaluate the safety of HPP after clinical
      transplantation.

PMID- 30292813
TI  - Brain functional and effective connectivity underlying the information processing
      speed assessed by the Symbol Digit Modalities Test.
AB  - Delayed Information Processing Speed (IPS) often underlies attention deficits and
      is particularly evident in patients with traumatic brain injury, Parkinson's
      disease, depression, dementia, and multiple sclerosis. Therefore, it is of
      interest to determine the brain network that is responsible for such essential
      cognitive function to understand IPS deficits and to develop effective
      rehabilitation programs. We assessed brain functional connectivity and effective
      connectivity during the performance of an adapted version of the Symbol Digit
      Modalities Test. Using dynamic causal modeling, we focused on obtaining a network
      model for IPS function in healthy subjects. Sixteen right-handed volunteers
      (seven women, age: 29.7 +/- 5.0 years) were included in the study after giving
      written consent for participating. Functional magnetic resonance images were
      acquired in a 3T scanner. According to our results, two systems interact during
      the IPS task performance. One is formed by frontoparietal and fronto-occipital
      networks, related to the control of goal-directed (top-down) selection for
      stimuli and response, while the second is composed of the temporoparietal and
      inferior frontal cortices, which are associated with stimulus-driven attention in
      the brain. Additionally, the default-mode network showed a significant
      correlation with networks positively associated with the task, mainly those
      related to visual detection and processing, indicating its relevant role in
      functional integration involving IPS. Therefore, an IPS-related network was
      proposed through a methodology that may be useful for future studies considering
      other cognitive functions and tasks, clinical groups, and longitudinal
      assessments.

PMID- 30292814
TI  - Dynamic 23Na MRI - A non-invasive window on neuroglial-vascular mechanisms
      underlying brain function.
AB  - A novel magnetic resonance imaging (MRI) acquisition and reconstruction method
      for obtaining a series of dynamic sodium 23Na-MRI acquisitions was designed to
      non-invasively assess the signal variations of brain sodium during a hand motor
      task in 14 healthy human volunteers on an ultra high field (7T) MR scanner.
      Regions undergoing activation and deactivation were identified with reference to
      conventional task-related BOLD functional MRI (fMRI). Activation observed in the
      left central regions, the supplementary motor areas and the left cerebellum
      induced an increase in the sodium signal observed at ultra short echo time and a
      decrease in the 23Na signal observed at long echo time. Based on a simple model
      of two distinct sodium pools (namely, restricted and mobile sodium), the ultra
      short echo time measures the totality of sodium whereas the long echo time is
      mainly sensitive to mobile sodium. This activation pattern is consistent with
      previously described processes related to an influx of Na+ into the intracellular
      compartments and a moderate increase in the cerebral blood volume (CBV). In
      contrast, deactivation observed in the right central regions ipsilateral to the
      movement, the precuneus and the left cerebellum induced a slight decrease in
      sodium signal at ultra short echo time and an increase of sodium signal at longer
      echo times. This inhibitory pattern is compatible with a slight decrease in CBV
      and an efflux of intracellular Na+ to the extracellular compartments that may
      reflect neural dendritic spine and astrocytic shrinkage, and an increase of
      sodium in the extracellular fraction. In conclusion, cerebral dynamic 23Na MRI
      experiments can provide access to the ionic transients following a functional
      task occurring within the neuro-glial-vascular ensemble. This has the potential
      to open up a novel non-invasive window on the mechanisms underlying brain
      function.

PMID- 30292815
TI  - On the scaling behavior of water diffusion in human brain white matter.
AB  - Development of therapies for neurological disorders depends on our ability to non
      invasively diagnose and monitor the progression of underlying pathologies at the
      cellular level. Physics and physiology limit the resolution of human MRI to be
      orders of magnitude coarser than cell dimensions. Here we identify and quantify
      the MRI signal coming from within micrometer-thin axons in human white matter
      tracts in vivo, by utilizing the sensitivity of diffusion MRI to Brownian motion
      of water molecules restricted by cell walls. We study a specific power-law
      scaling of the diffusion MRI signal with the diffusion weighting, predicted for
      water confined to narrow axons, and quantify axonal water fraction and
      orientation dispersion.

PMID- 30292816
TI  - Proteomic and metabolomic approaches in the search for biomarkers in chronic
      kidney disease.
AB  - Chronic kidney disease (CKD) is an aging-related disorder that represents a major
      global public health burden. Current biochemical biomarkers, such as serum
      creatinine and urinary albumin, have important limitations when used to identify
      the earliest indication of CKD or in tracking the progression to more advanced
      CKD. These issues underline the importance of finding and testing new molecular
      biomarkers that are capable of successfully meeting this clinical need. The
      measurement of changes in nature and/or levels of proteins and metabolites in
      biological samples from patients provide insights into pathophysiological
      processes. Proteomic and metabolomic techniques provide opportunities to record
      dynamic chemical signatures in patients over time. This review article presents
      an overview of the recent developments in the fields of metabolomics and
      proteomics in relation to CKD. Among the many different proteomic biomarkers
      proposed, there is particular interest in the CKD273 classifier, a urinary
      proteome biomarker reported to predict CKD progression and with implementation
      potential. Other individual non-invasive peptidomic biomarkers that are
      potentially relevant for CKD detection include type 1 collagen, uromodulin and
      mucin-1. Despite the limited sample sizes and variability of the metabolomics
      studies, some metabolites such as trimethylamine N-oxide, kynurenine and
      citrulline stand out as potential biomarkers in CKD.

PMID- 30292817
TI  - Associations of dietary protein intake with bone mineral density: An
      observational study in 70,215 UK Biobank participants.
AB  - PURPOSE: Adequate dietary protein intake is important for the maintenance of bone
      health; however, data in this area is ambiguous with some suggestion that high
      protein intake can have deleterious effects on bone health. The aim of the
      current study was to explore the associations of protein intake with bone mineral
      density (BMD). METHODS: We used baseline data from the UK Biobank (participants
      aged 40-69 years) to examine the association of protein intake with BMD (measured
      by ultrasound). These associations were examined, in women (n = 39,066) and men
      (n = 31,149), after adjustment for socio-demographic and lifestyle confounders
      and co-morbidities. RESULTS: Protein intake was positively and linearly
      associated with BMD in women (beta-coefficient 0.010 [95% CI 0.005; 0.015, p <
      0.0001]) and men (beta-coefficient 0.008 [95% CI 0.000; 0.015, p = 0.044]); per
      1.0 g/kg/day increment in protein intake, independently of socio-demographics,
      dietary factors and physical activity. CONCLUSIONS: The current data have
      demonstrated that higher protein intakes are positively associated with BMD in
      both men and women. This indicates that higher protein intakes may be beneficial
      for both men and women.

PMID- 30292818
TI  - Denosumab effects on bone density and turnover in postmenopausal women with low
      bone mass with or without previous treatment.
AB  - PURPOSE: Prior osteoporosis therapies may affect the skeletal response to
      denosumab. We compared the effect of denosumab (60 mg every 6 months for 12
      months) on bone mineral density and bone metabolism parameters in postmenopausal
      women with low bone mass who were either treatment-naive (n = 30), or previously
      treated either with zoledronic acid (n = 30), or teriparatide (n = 22). METHODS:
      We assessed lumbar spine bone mineral density (BMD) and measured serum
      concentrations of the bone turnover markers pro-collagen type 1 N-terminal
      propeptide (PINP) and C-terminal-cross-linking telopeptide of type 1 collagen
      (CTX), as well as sclerostin, dickkopf-1 (Dkk-1), and myostatin. RESULTS: Lumbar
      spine BMD increased equivalently in all three groups after 12 months of denosumab
      compared to baseline (p < 0.001). Serum PINP and CTX decreased significantly with
      denosumab in pre-treated women reaching the same nadir levels as in treatment
      naive patients (p < 0.001). Women pre-treated with teriparatide displayed lower
      baseline myostatin concentrations as compared to the other two groups (p <
      0.001). Changes in lumbar spine BMD in teriparatide pre-treated women correlated
      with changes in bone turnover markers and myostatin. CONCLUSIONS: Denosumab
      induced similar increases in lumbar spine BMD in treatment-naive and pre-treated
      patients and suppressed serum PINP and CTX to the same levels regardless of prior
      treatments. In teriparatide pre-treated patients the magnitude of change in bone
      turnover markers is associated with BMD response.

PMID- 30292819
TI  - Biochemical and Structural Characterization of TesA, a Major Thioesterase
      Required for Outer-Envelope Lipid Biosynthesis in Mycobacterium tuberculosis.
AB  - With the high number of patients infected by tuberculosis and the sharp increase
      of drug-resistant tuberculosis cases, developing new drugs to fight this disease
      has become increasingly urgent. In this context, analogs of the naturally
      occurring enolphosphates Cyclipostins and Cyclophostin (CyC analogs) offer new
      therapeutic opportunities. The CyC analogs display potent activity both in vitro
      and in infected macrophages against several pathogenic mycobacteria including
      Mycobacterium tuberculosis and Mycobacterium abscessus. Interestingly, these CyC
      inhibitors target several enzymes with active-site serine or cysteine residues
      that play key roles in mycobacterial lipid and cell wall metabolism. Among them,
      TesA, a putative thioesterase involved in the synthesis of phthiocerol
      dimycocerosates (PDIMs) and phenolic glycolipids (PGLs), has been identified.
      These two lipids (PDIM and PGL) are non-covalently bound to the outer cell wall
      in several human pathogenic mycobacteria and are important virulence factors.
      Herein, we used biochemical and structural approaches to validate TesA as an
      effective pharmacological target of the CyC analogs. We confirmed both
      thioesterase and esterase activities of TesA, and showed that the most active
      inhibitor CyC17 binds covalently to the catalytic Ser104 residue leading to a
      total loss of enzyme activity. These data were supported by the X-ray structure,
      obtained at a 2.6-A resolution, of a complex in which CyC17 is bound to TesA. Our
      study provides evidence that CyC17 inhibits the activity of TesA, thus paving the
      way to a new strategy for impairing the PDIM and PGL biosynthesis, potentially
      decreasing the virulence of associated mycobacterial species.

PMID- 30292820
TI  - Regulation of Mitochondrial Electron Transport Chain Assembly.
AB  - Mitochondrial function depends on the correct synthesis, transport, and assembly
      of proteins and cofactors of the electron transport chain. The initial idea that
      the respiratory chain protein complexes (RCCs) were independent structures in the
      inner mitochondrial membrane evolved after the identification of higher
      quaternary structures called supercomplexes (SCs), whose formation is dynamically
      regulated in order to accommodate cellular metabolic demands. Due to the dual
      genetic origin of the mitochondrial proteome, electron transport chain and SCs
      formation must be tightly regulated to coordinate the expression and assembly of
      components encoded by both genomes. This regulation occurs at different levels
      from gene transcription to protein, complex or SCs assembly, and might involve
      the participation of factors that contribute to the formation and stability of
      the RCCs and SCs. Here we review the cellular pathways and assembly factors that
      regulate RCCs and SCs formation.

PMID- 30292821
TI  - Biofilm-derived spores of Clostridioides (Clostridium) difficile exhibit
      increased thermotolerance compared to planktonic spores.
AB  - Biofilm-derived spores of strains of four ribotypes (001, 020, 027 & 078) of
      Clostridioides (Clostridium) difficile were found to exhibit increased
      thermotolerance compared to spores produced in planktonic culture. In addition,
      'thick' and 'thin' exosporium morphotypes described previously were visualised by
      electron microscopy in both biofilm and planktonic spores.

PMID- 30292822
TI  - The non-toxigenic strain of Clostridioides difficile Z31 can prevent infection by
      C. difficile in experimental model piglets.
AB  - One of the main challenges associated with Clostridioides difficile infection
      (CDI) in humans and domestic animals is the lack of an effective preventive
      strategy. One strategy with promising results is the oral administration of non
      toxigenic strains of C. difficile (NTCD). Recently, Z31, a NTCD strain isolated
      from a healthy dog, showed promising results to prevent CDI in hamsters. Thus,
      the present study aimed to evaluate the capacity of Z31 to prevent CDI in piglets
      using an experimental model. Twenty neonatal piglets were randomly distributed in
      three groups: G1 - 106 spores of Z31 followed by 107 spores of a toxigenic C.
      difficile strain (n = 7), G2 (positive control) - 107 spores of a toxigenic C.
      difficile strain (n = 7), and G3 (negative control) - no biological inoculum (n =
      6). All animals were kept in individual insulators and observed for 60 h. Data
      regarding clinical signs, macro and microscopic lesions, toxigenic culture of C.
      difficile, and detection of A/B toxins in the feces were evaluated. All evaluated
      parameters were significantly lower in animals that received Z31 compared to the
      positive control. Thus, oral administration of Z31 was able to prevent CDI in
      piglets in an experimental model.

PMID- 30292823
TI  - A quantitative method for evaluating cortical responses to electrical
      stimulation.
AB  - BACKGROUND: Electrical stimulation of the cortex using subdurally implanted
      electrodes can causally reveal structural connectivity by eliciting cortico
      cortical evoked potentials (CCEPs). While many studies have demonstrated the
      potential value of CCEPs, the methods to evaluate them were often relatively
      subjective, did not consider potential artifacts, and did not lend themselves to
      systematic scientific investigations. NEW METHOD: We developed an automated and
      quantitative method called SIGNI (Stimulation-Induced Gamma-based Network
      Identification) to evaluate cortical population-level responses to electrical
      stimulation that minimizes the impact of electrical artifacts. We applied SIGNI
      to electrocorticographic (ECoG) data from eight human subjects who were implanted
      with a total of 978 subdural electrodes. Across the eight subjects, we delivered
      92 trains of approximately 200 discrete electrical stimuli each (amplitude 4-15
      mA) to a total of 64 electrode pairs. RESULTS: We verified SIGNI's efficacy by
      demonstrating a relationship between the magnitude of evoked cortical activity
      and stimulation amplitude, as well as between the latency of evoked cortical
      activity and the distance from the stimulated locations. CONCLUSIONS: SIGNI
      reveals the timing and amplitude of cortical responses to electrical stimulation
      as well as the structural connectivity supporting these responses. With these
      properties, it enables exploration of new and important questions about the
      neurophysiology of cortical communication and may also be useful for pre-surgical
      planning.

PMID- 30292824
TI  - Quantitative and qualitative assessment of glymphatic flux using Evans blue
      albumin.
AB  - BACKGROUND: The glymphatic system is a proposed pathway for clearance of proteins
      and macromolecules from brain, and disrupted glymphatic flux is implicated in
      neurological disease. We capitalized on colorimetric, fluorescent, and protein
      binding properties of Evans blue to evaluate glymphatic flux. NEW METHOD: Twenty
      five MUL of 1% Evans blue-labeled albumin (EBA) in artificial cerebrospinal fluid
      (aCSF) was injected into the intracisternal space of anesthetized postnatal day
      17 rats. Serum was collected at various time points after injection (n = 37) and
      EBA was measured spectrophotometrically. In separate rats (n = 3), a cranial
      window was placed over the parietal cortex and EBA transit was evaluated using in
      vivo multiphoton microscopy. Separate rats (n = 6) were processed for
      immunohistochemistry to examine localization of EBA. In some rats, intracranial
      pressure (ICP) was increased via intracisternal injection of aCSF. RESULTS: EBA
      was detected in serum as early as 30 min, was maximal at 4 h, and was
      undetectable at 72 h after intracisternal injection. Using intra-vital microscopy
      and immunohistochemistry EBA could be tracked from CSF to perivascular locations.
      Consistent with removal via glymphatic flux, increasing ICP to 40 mmHg
      accelerated transit of EBA from CSF to blood. COMPARISON WITH EXISTING METHODS:
      Transit of EBA from CSF to serum could be quantified spectrophotometrically
      without radioactive labeling. Glymphatic flux could also be qualitatively
      evaluated using EBA fluorescence. CONCLUSION: We present a novel technique for
      simultaneous quantitative and qualitative evaluation of glymphatic flux in rats.

PMID- 30292825
TI  - Oral health and microbiota status in professional rugby players: A case-control
      study.
AB  - OBJECTIVE: Elite athletes are prone to develop oral diseases, which could
      increase the risk for injuries. The aim of this study was to evaluate the oral
      health and the composition of oral microbiota of elite rugby players compared to
      the general population. METHODS: We set up a case-control study by screening 24
      professional rugby players (PRG) and 22 control patients (CG) for dental and
      gingival examinations and performed a taxonomic analysis and a predicted
      functional analysis of oral microbiota. RESULTS: The Decay, Missing and Filled
      (DMF) teeth index (5.54 +/- 6.18 versus 2.14 +/- 3.01; p = 0.01) and the
      frequency of gingivitis (58,33% versus 13.63%) were significantly increased in
      PRG compared to CG. PRG were characterized by a dysbiotic oral microbiota
      (Shannon Index: 3.32 +/- 0.62 in PRG versus 3.79 +/- 0.68 in CG; p = 0.03) with
      an increase of Streptococcus (58.43 +/- 16.84 versus 42.60 +/- 17.45; p = 0.005),
      the main genus implicated in caries. Predicted metagenomics of oral microbiota in
      rugby players was suggestive of a cariogenic metagenome favourable to the
      development of caries. CONCLUSIONS: Our study shows that the oral health of PRG
      was poorer than the general population. PRG are characterized by a dysbiotic oral
      microbiota with an increase of the relative abundance of Streptococcus genus,
      positively correlated to the weight and negatively correlated to the diversity of
      oral microbiota. CLINICAL SIGNIFICANCE: Dental screening should be included in
      the medical follow-up of professional rugby players as a part of their health
      management. New strategies such as using probiotics like Lactobacillus could help
      to control the dysbiosis of oral microbiota.

PMID- 30292826
TI  - Influence of corticosterone on growth, home-cage activity, wheel running, and
      aerobic capacity in house mice selectively bred for high voluntary wheel-running
      behavior.
AB  - Glucocorticoids, a class of metabolic hormones, impact a wide range of traits
      (e.g., behavior, skeletal growth, muscle maintenance, glucose metabolism), and
      variation in concentrations of circulating glucocorticoids (such as
      corticosterone), at the level of natural individual variation, in relation to
      endocrine disorders, or from exogenous supplementation, have manifold effects.
      Changes in circulating corticosterone concentrations can also impact multiple
      aspects of locomotor behavior, including both motivation and physical ability for
      exercise. To examine further the role of corticosterone in locomotor behavior and
      associated traits, we utilized laboratory house mice from a long-term experiment
      that selectively breeds for high levels of voluntary exercise. As compared with
      four non-selected control (C) lines, mice from the four replicate High Runner
      (HR) lines have ~2-fold higher baseline circulating corticosterone concentrations
      as well as ~3-fold higher voluntary wheel running on a daily basis, higher home
      cage activity when deprived of wheels, higher maximal aerobic capacity, and
      smaller body size; potentially, all of these differences could be modulated by
      circulating corticosterone. We administered 50 MUg/mL corticosterone-21
      hemisuccinate in the drinking water of both HR and C male mice from weaning
      through ~8 weeks of age. As compared with mice from C lines, HR mice had higher
      endogenous corticosterone levels; higher daily wheel-running distance, duration,
      and speed; higher maximal oxygen consumption during forced exercise (VO2max);
      spent more time in the closed arms of an elevated plus maze; and had larger
      reproductive fat pads. For both HR and C mice, corticosterone treatment strongly
      suppressed endogenous circulating corticosterone levels, decreased growth rate
      and adult body mass, increased food and water consumption (both adjusted for body
      mass), increased entries into closed arms of an elevated plus maze, decreased
      home-cage activity (total and average intensity), decreased wheel-running
      distance and maximum speed, and decreased VO2max. At the suborganismal level,
      corticosterone treatment decreased relative adrenal, liver, and triceps surae
      muscle mass, as well as tail length, but increased both subdermal and
      reproductive fat pad masses, as well as hematocrit. Overall, the responses of
      both HR and C mice to corticosterone supplementation were "negative" from a
      health perspective. These results have significant implications for understanding
      both the evolution of baseline corticosterone levels and stress-related effects
      on activity levels. They also suggest that patients experiencing extended periods
      of glucocorticoid treatment might benefit from attempts to increase their
      physical activity as an adjuvant.

PMID- 30292827
TI  - Effects of ovarian hormones on emotional behaviors in dopamine D3 receptor
      knockout mice.
AB  - Ovarian hormones reportedly have beneficial effects on affective behaviors.
      However, the functions of ovarian hormones in neurotransmitter signaling must be
      identified to understand their role in anxiety and depression. Several studies
      have provided evidence of the relationship between ovarian hormones and the
      dopaminergic system, but the interaction between ovarian hormones and dopamine D3
      receptor (DRD3) is poorly understood. The aim of the present study was to examine
      the role of DRD3 in the anxiety-like and depression-like behavioral changes
      induced by estrogen and progesterone. We subjected D3 receptor knockout (D3KO)
      and wild-type (WT) mice to a series of behavioral tests. Mice were ovariectomized
      4 weeks before testing, and we randomly administered 17beta-estradiol (E2, 0.2
      mg/kg), progesterone (P4, 10 mg/kg), E2 (0.2 mg/kg) plus P4 (10 mg/kg) or vehicle
      (VEH, corn oil, 0.2 ml) subcutaneously daily for 9 consecutive days, starting 4
      days before the testing day. On the testing day, the mice were injected 30 min
      prior to behavioral testing. Compared with WT mice in the same treatment group,
      D3KO mice displayed hyperactivity in the light-dark box test (LDBT) but lower
      activity in the open field test (OFT). In addition, D3KO mice but not their WT
      littermates showed behavioral changes after E2 treatment compared with those
      after VEH treatment in the LDBT only. In depression tests, D3KO-VEH mice
      displayed significantly longer immobility times than did WT-VEH mice. In
      addition, only D3KO mice exhibited an obvious decrease in immobility time after
      E2 and P4 administration. These results indicate that the anxiolytic and
      antidepressant effects of ovarian hormones can be influenced by DRD3 expression
      and that DRD3 knockout may induce varying sensitivities to ovarian hormones that
      depend on various factors, including test paradigms and experiences in animal
      models. Our research provides a novel insight, i.e., DRD3 may play a role in the
      efficacy of hormone therapy.

PMID- 30292828
TI  - Alpha pinene modulates UVA-induced oxidative stress, DNA damage and apoptosis in
      human skin epidermal keratinocytes.
AB  - AIMS: This study aims to evaluate the protective effect of alpha pinene (AP), an
      essential oil monoterpene, against ultraviolet-A (UVA; 320-400 nm) induced
      cellular damages in human skin epidermal keratinocytes (HaCaT cells). MATERIALS
      AND METHODS: In this study, HaCaT cells were subjected to single UVA-irradiation
      (10 J/cm2) in the presence and absence of AP (30 MUM) then different cellular end
      points were analyzed. The protective effect of AP against UVA-induced
      cytotoxicity was evaluated by MTT-based metabolic assay. Generation of reactive
      oxygen species (ROS), alteration of mitochondrial membrane potential (MMP), DNA
      single- and double strand breaks (SSBs and DSBs) and apoptotic morphological
      changes during different treatment conditions were measured by fluorescence
      microscopy and spectrofluorometry. Modulatory role of AP against UVA-mediated
      inflammatory markers expression, nucleotide excision repair (NER) proteins and
      apoptotic markers expression during AP and/or UVA treatment were studied by
      western blot. KEY FINDINGS: Pretreatment with AP prevented UVA-induced
      cytotoxicity, generation of ROS, lipid peroxidation and DNA stand breaks probably
      through its antioxidant property. AP also inhibited UVA-induced inflammatory
      mediators such as NF-kappaB, TNF-alpha and IL-6 expression in HaCaT cells.
      Further, AP modulates NER proteins via activation of p53 and p21 thereby
      subsequently prevent the formation of UVA-induced cyclobutane pyrimidine dimers
      (CPDs). We also noticed that AP inhibits apoptotic cell death by preventing UVA
      induced loss of mitochondrial membrane potential through modulating Bax/Bcl-2
      expression in HaCaT cells. SIGNIFICANCE: The present findings suggest that AP
      prevent UVA-induced oxidative stress, inflammation, DNA damages and apoptosis in
      human skin cells.

PMID- 30292829
TI  - Hepatic injury induced by thioacetamide causes aortic endothelial dysfunction by
      a cyclooxygenase-dependent mechanism.
AB  - : Liver cirrhosis is associated with a wide range of cardiovascular abnormalities
      including hyperdynamic circulation and cirrhotic cardiomyopathy. The pathogenic
      mechanisms of these cardiovascular changes are multifactorial and include
      vascular dysregulations. AIM: The present study tested the hypothesis that the
      systemic vascular hyporesponsiveness in thioacetamide (TAA)-induced liver injury
      model is dependent on nitric oxide (NO) and cyclooxygenase (COX) derivatives.
      MAIN METHODS: Wistar rats were treated with TAA for eight weeks to induce liver
      injury. KEY FINDINGS: The maximal contractile response in concentration-effect
      curves to phenylephrine was decreased in aorta from TAA-treated rats, but no
      differences were found in aorta without endothelium, suggesting an endothelium
      dependent mechanism in decreased contractile response. There was no difference in
      the contractile response with and without L-NAME (N(omega)-nitro-l-arginine
      methyl ester) in rats with liver injury, showing that the TAA treatment impairs
      NO synthesis. Pre-incubation of the aorta with indomethacin, a COX-inhibitor,
      normalized the reduced contractile response to phenylephrine in arteries from TAA
      group. Also, COX-2 and iNOS (inducible nitric oxide syntase) protein expression
      was increased in aorta from TAA group compared to control group. Animals
      submitted to TAA treatment had a reduction in systolic blood pressure. Our
      findings demonstrated that liver injury induced by TAA caused a decrease in
      aortic contractile response by a COX-dependent mechanism but not by NO release.
      Also, it was demonstrated an inflammatory process in the aorta of TAA-treated
      rats by increased expression of COX-2 and iNOS. SIGNIFICANCE: Therefore, there is
      an essential contribution of COX-2 activation in extra-hepatic vascular
      dysfunction and inflammation present in cirrhosis induced by TAA.

PMID- 30292830
TI  - Sirtuin-1 protects hair follicle stem cells from TNFalpha-mediated inflammatory
      stress via activating the MAPK-ERK-Mfn2 pathway.
AB  - OBJECTIVE: Stem cell transplantation is a promising tool to treat burn injuries.
      However, the inflammatory microenvironment in damaged skin limits the efficiency
      of stem cell-based therapy via poorly understood mechanisms. The aim of our study
      is to explore the contribution and mechanism of Sirtuin-1 (Sirt1) in TNFalpha
      mediated inflammatory stress in hair follicle stem cells (HFSCs). METHODS:
      Cellular viability was determined using the MTT assay, TUNEL staining, western
      blot analysis and LDH release assay. Adenovirus-loaded Sirt1 was transduced into
      HFSCs to overexpress Sirt1 in the presence of TNFalpha. Mitochondrial function
      was determined using JC-1 staining, mitochondrial ROS staining,
      immunofluorescence staining and western blotting. RESULTS: Sirt1 was
      downregulated in response to the TNFalpha treatment. Additionally, TNFalpha
      stress reduced the viability, mobility and proliferation of HFSCs, and these
      effects were reversed by the overexpression of Sirt1. At the molecular level,
      Sirt1 overexpression attenuated TNFalpha-mediated mitochondrial damage, as
      evidenced by increased mitochondrial energy metabolism, decreased mitochondrial
      ROS generation, stabilized mitochondrial potential and blockage of the
      mitochondrial apoptotic pathway. Furthermore, Sirt1 modulated mitochondrial
      homeostasis by activating the MAPK-ERK-Mfn2 axis; inhibition of this pathway
      abrogated the protective effects of Sirt1 on HFSC survival, migration and
      proliferation. SIGNIFICANCE: Based on our results, the inflammatory stress
      mediated HFSC injury may be associated with a decrease in Sirt1 expression and
      subsequent mitochondrial dysfunction. Accordingly, strategies designed to enhance
      Sirt1 expression would be an effective approach to enhance the survival of HFSCs
      in the inflammatory microenvironment.

PMID- 30292831
TI  - Inhibition of SRC/FAK cue: A novel pathway for the synergistic effect of
      rosuvastatin on the anti-cancer effect of dasatinib in hepatocellular carcinoma.
AB  - PURPOSE: Statins extended their hypocholestremic effect to show a promising
      anticancer activity. Hepatocellular carcinoma (HCC), the third common cause of
      cancer-related death, responded positively to statins. Some in-vitro studies
      reveal the rosuvastatin antitumor effect, but barely in-vivo studies. Hence, we
      evaluated the antitumor potential of rosuvastatin in a HCC model, the possible
      signaling cues involved, and whether it augments the dasatinib anticancer effect.
      METHOD: For the in-vitro study, the IC50 and the combination (CI)/dose reduction
      (DRI) indices were determined for HCC cell line (HepG2) treated with dasatinib
      and/or rosuvastatin. For the in-vivo study, mice with diethylnitrosamine-induced
      HCC were treated for 21 days with dasatinib and/or rosuvastatin (10 and 20 mg/kg,
      respectively). The p-focal adhesion kinase/p-rous sarcoma oncogene cellular
      homolog (p-FAK/p-Src) cascade and its downstream molecules were assessed.
      RESULTS: The in-vitro study confirmed the synergistic effect of rosuvastatin with
      dasatinib, which entailed the in-vivo results. The two drugs decreased the p
      FAK/p-Src cue along with p-Ras/c-Raf, p-STAT-3, and p-Akt levels to enhance
      apoptosis by an increase in caspase-3 level and a decline in survivin level.
      Additionally, they inhibited HGF, VEGF, and the MMP-9. Moreover, the different
      treatments downregulated the expression of proliferative cell nuclear antigen
      (PCNA) and Ki-67. The best effect was mediated by the combination regimen that
      surpassed the effect of either drug alone. CONCLUSION: Our results highlighted
      some of the signals involved in rosuvastatin antitumor effect and nominate it as
      an adds-on therapy with dasatinib to yield a better effect in HCC through
      inhibiting the FAK/Src cascade.

PMID- 30292832
TI  - FAK alleviates radiation-induced rectal injury by decreasing apoptosis.
AB  - Radiation-induced rectal injury is closely related with radiotherapy efficiency.
      Here, we investigated the effect of focal adhesion kinase (FAK) in radiation
      induced rectal injury. Peripheral blood samples of patients with rectal cancer
      were collected prior to radiotherapy. Differentially expressed genes and copy
      number variations (CNVs) were analyzed by microarray analysis. The CTCAE v3.0
      toxicity grades were used to assess acute rectal injury. The radiosensitivity of
      human intestinal epithelial crypt (HIEC) cells were assayed by colony formation,
      mitochondrial membrane potential, flow cytometry and western blotting. The
      rectums of C57BL/6 mice were X-irradiated locally with a single dose of 15 Gy.
      The effect of FAK on radiation-induced injury was investigated by hematoxylin
      eosin (H&E) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling (TUNEL), immunohistochemistry (IHC) and quantitative real-time PCR
      (qRT-PCR). FAK mRNA level was inversely correlated with rectal injury severity in
      patient samples. A CNV amplification located on chromosome 8 was closely related
      with FAK. Further functional assays revealed increased levels of gammaH2AX
      expression and apoptosis-related proteins in FAK-silenced HIEC cells. The ratio
      of TUNEL, cl-caspase-3, cyto-c and bax/bcl-2 expression in the rectum mucosa
      treated with a FAK inhibitor increased significantly. These results demonstrated
      that FAK reduced radiation-induced rectal injury by decreasing apoptosis.

PMID- 30292833
TI  - Nicotinamide mononucleotide alleviates Aluminum induced bone loss by inhibiting
      the TXNIP-NLRP3 inflammasome.
AB  - Aluminum (Al) recognized as a persistent environmental contaminant is associated
      with bone diseases. Nicotinamide mononucleotide (NMN) is an intermediate of
      nicotinamide adenine dinucleotide (NAD+) biosynthesis widely used to replenish
      NAD+. Increasing evidences demonstrated that replenishment of NAD+ can protect
      against bone loss. However, the potentially protective effects of NMN against Al
      induced bone impairment and the underlying mechanisms remain unknown. In the
      present study, we sought to investigate the protective effects of NMN on Al
      induced bone damages and elucidate the potential mechanisms. We orally exposed
      AlCl3 (10 mg/L) to Sprague-Dawley rats in drinking water for 12 weeks while NMN
      (20 mg/kg) were intraperitoneally injected in last 4 weeks. We found that Al
      could induce bone damages, bone loss and oxidative stress. In addition, we showed
      that Al triggered inflammatory responses, which is mediated by the NOD-like
      receptor pyrin domain containing 3 (NLRP3) inflammasome activation. However, NMN
      treatment significantly alleviated Al-induced bone injuries by decreasing bone
      loss, suppressing oxidative stress as well as inhibiting Thioredoxin-interacting
      protein (TXNIP)-NLRP3 inflammasome pathway and pro-inflammatory cytokine
      production in vivo and in vitro. Meanwhile, treatment with TXNIP siRNA performed
      the same protective effects as NMN in Al-treated MC3T3-E1 cells. Collectively,
      our results suggest that NMN may reduce Al-induced bone loss partly by
      suppression of the TXNIP-NLRP3 inflammasome pathway.

PMID- 30292834
TI  - Solubility changes of promyelocytic leukemia (PML) and SUMO monomers and dynamics
      of PML nuclear body proteins in arsenite-treated cells.
AB  - Promyelocytic leukemia (PML) and a suite of other proteins form nuclear bodies
      (NBs) where SUMOylation of PML and tumor suppression events occur in response to
      arsenite (As3+) treatment. Soluble PML is rapidly modified to the insoluble form
      in response to As3+, yet the relationship between the solubility change and
      nuclear localization of PML and PML-nuclear body (PML-NB) proteins remained
      elusive. We have investigated differences in the solubility change of well-known
      PML-NB proteins such as death-associated protein 6 (DAXX), SUMO, and PML in
      genetically engineered HEK293, and Jurkat and HL60 cells. The solubility of PML
      and SUMO2/3 monomers in RIPA solution decreased in 2 h in response to As3+. Live
      image analysis of GFP-PML revealed that extranuclear PML was insoluble in RIPA
      irrespective of the As3+-treatment and PML in PML-NBs, which was soluble in the
      untreated cells, was converted to insoluble forms by As3+. The solubility of DAXX
      was not changed by As3+, even though PML and DAXX co-localized completely in the
      subcellular compartments. Murine double mutant 2 (MDM2), which is known to
      interacts with intranuclear PML, did not affect the As3+-induced solubility
      change of PML. These results indicate that As3+ selectively reorganizes PML and
      SUMO2/3 monomers into insoluble forms in PML-NBs, and then PML SUMOylation
      proceeds.

PMID- 30292835
TI  - TFG-RARA: A novel fusion gene in acute promyelocytic leukemia that is responsive
      to all-trans retinoic acid.

PMID- 30292836
TI  - Body appreciation in British men: Correlates and variation across sexual
      orientation.
AB  - Investigations of positive body image among men and across various social
      identities are lacking, and could contribute to a more complete understanding of
      the construct, including how positive body image can be improved. This study
      addressed this gap by investigating correlates of body appreciation - a key facet
      of positive body image - in men, and testing whether levels of body appreciation
      vary across sexual orientation. Data from a British community sample of 439 men
      (Mage = 39.13) showed that body appreciation inversely correlated with conformity
      to masculine norms and upward appearance-based social comparisons, and positively
      correlated with physical activity. Body appreciation was lower among sexual
      minority compared to heterosexual men, and athletic appearance-ideal
      internalisation and upward appearance-based social comparisons mediated this
      relationship. Replicating prior research among men, body appreciation positively
      correlated with body satisfaction, and inversely correlated with perceived
      appearance pressures from media and eating pathology. These findings have
      implications for interventions addressing body image among men.

PMID- 30292837
TI  - Quantitative MRI analysis of infrapatellar and suprapatellar fat pads in normal
      controls, moderate and end-stage osteoarthritis.
AB  - The aim of this study was to analyze the magnetic resonance imaging (MRI)
      volumetric and morphometric characteristics of the infrapatellar fat pad (IFP)
      and the suprapatellar fat pad (SFP) in normal controls, moderate and end-stage
      osteoarthritis (OA) patients. Forty-four MRI images of the three groups were
      collected: a) 17 patients undergoing meniscectomy with Outerbridge score 0
      (control group); b) 15 patients undergoing meniscectomy with Outerbridge score
      3/4 (moderate OA group); and c) 12 patients undergoing total knee replacement
      (end-stage OA group). Volume, depth, femoral and tibial arch lengths of IFP were
      quantified. The hypointense IFP signals were also scored. The SFP volume,
      oblique, antero-posterior and cranio-caudal lengths were determined. IFP and SFP
      characteristics were compared between groups. A decrease of IFP volume, depth,
      femoral, and tibial arch lengths in moderate and end-stage OA compared to
      controls were observed. A difference in IFP hypointense signal was found between
      groups. No differences were found in SFP characteristics between the groups. In
      controls and moderate OA patients, correlations were found among the different
      MRI characteristics of both IFP and SFP, while in the end-stage OA group
      correlations were found only in SFP. We evidenced differences of the IFP MRI
      morphometric characteristics between the groups analyzed, supporting an important
      role of IFP in OA pathology and progression. On the contrary, no differences were
      highlighted in SFP analysis suggesting that this fat pad is not clearly involved
      in OA, probably due to its peculiar localization and different function.

PMID- 30292838
TI  - New triterpenoid saponins from the leaves of Ilex chinensis.
AB  - Eight new triterpenoid saponins, including four ursane-type saponins,
      ilexchinenosides J-M (1-4), and four oleanane-type saponins, ilexchinenosides N-Q
      (5-8), along with three known triterpenoid saponins (9-11) were isolated from the
      leaves of Ilex chinensis Sims. Their structures were established by 1D, 2D NMR
      and MS spectroscopic analyses and through comparisons with known compounds.
      Moreover, compounds 1, 3, 5, 7-9 and 11 exhibited significant levels of
      hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2
      cell damage in in vitro assays while compound 10 had moderately inhibitory
      effects on the NO production of lipopolysaccharide (LPS)-induced murine
      macrophages.

PMID- 30292839
TI  - Bisphenol S (BPS) triggers the migration of human non-small cell lung cancer
      cells via upregulation of TGF-beta.
AB  - As one of the leading causes of cancer deaths world-wide, the progression of
      human non-small cell lung cancer (NSCLC) can be regulated by estrogenic signals.
      Our present data showed that an industrial endocrine disrupting chemical,
      bisphenol S (BPS), can promote the in vitro migration of NSCLC cells, which was
      evidenced by the upregulation of vimentin and matrix metalloproteinase-2 (MMP-2).
      BPS can increase the mRNA and protein expression of IL-10 and TGF-beta. While
      only targeted inhibition of TGF-beta can block BPS induced migration of NSCLC
      cells. The upregulation of TGF-beta can further activate the Smad-2/3 pathways.
      Further, BPS induced expression of TGF-beta was ERalpha/beta or G protein-coupled
      estrogen receptor (GPER) independent, since targeted inhibition of ERalpha/beta
      or GPER had no effect on BPS induced transcription of TGF-beta. We identified
      that the inhibitor of ERK1/2 can attenuate BPS induced expression of TGF-beta and
      activation of Smad-2/3 pathways. Collectively, we found that nanomolar BPS can
      trigger the in vitro migration of NSCLC cells via ERK1/2 mediated activation of
      TGF-beta/Smad-2/3 pathways.

PMID- 30292840
TI  - Widespread distribution of tauopathy in preclinical Alzheimer's disease.
AB  - The objective of this study was to examine the distribution and severity of tau
      PET binding in cognitively normal adults with preclinical Alzheimer's disease as
      determined by positive beta-amyloid PET. 18F-AV-1451 tau-PET data from 109
      cognitively normal older adults were processed with 34 cortical and 9 subcortical
      FreeSurfer regions and averaged across both hemispheres. Individuals were
      classified as being beta-amyloid positive (N = 25, A+) or negative (N = 84, A-)
      based on a 18F-AV-45 beta-amyloid-PET standardized uptake value ratio of 1.22. We
      compared the tau-PET binding in the 2 groups using covariate-adjusted linear
      regressions. The A+ cohort had higher tau-PET binding within 8 regions:
      precuneus, amygdala, banks of the superior temporal sulcus, entorhinal cortex,
      fusiform gyrus, inferior parietal cortex, inferior temporal cortex, and middle
      temporal cortex. These findings, consistent with preclinical involvement of the
      medial temporal lobe and parietal lobe and association regions by tauopathy,
      emphasize that therapies targeting tauopathy in Alzheimer's disease could be
      considered before the onset of symptoms to prevent or ameliorate cognitive
      decline.

PMID- 30292841
TI  - Exploring Shared Mental Models of surgical teams in Video-Assisted Thoracoscopic
      Surgery lobectomy.
AB  - BACKGROUND: Non-technical skills are important for safe and efficient surgery.
      Teams performing Video-Assisted Thoracoscopic Surgery (VATS) lobectomy express
      that it is of utmost importance to have a Shared Mental Model (SMM) of the
      patient, current situation, and team resources. However, these SMMs have never
      been explored in a clinical setting. The aim of this observational study was to
      measure the similarity of SMMs within teams performing VATS lobectomy. METHODS:
      In this national, multi-center study, SMMs of teams performing VATS lobectomy
      (n=64) were measured by pre- and postoperative questionnaires that were completed
      by all team members (n=172). Participants' responses were compared within each
      team to explore SMMs of risk assessment, familiarity, technical skills, non
      technical skills, and problems. RESULTS: Analysis showed poor agreement between
      team members with respect to risk assessment, but higher levels of agreement were
      found for assessments of familiarity, technical and non-technical skills within
      the team (Cronbach's alpha=0.90), most notably for surgical subteams
      (=surgeon+assistant surgeon+surgical nurses). During the surgical procedure, the
      most frequent problems were related to anesthesia, and these were most often
      recognized by the surgeons. The operating room nurses were the least aware of
      each other's and the surgeons' problems. CONCLUSIONS: Significant variation
      exists in the SMMs among VATS team members, with poor agreement regarding the
      patient and current situation, but better agreement with respect to team
      resources. Focus on pre-operative and peri-operative team reflexivity, in
      addition to explicit communication within unfamiliar teams, may provide
      opportunities to enhance SMMs, with possible downstream effects on team
      performance.

PMID- 30292842
TI  - Predictors of Failure of Medical Management in Uncomplicated Type B Aortic
      Dissection.
AB  - BACKGROUND: Optimal medical therapy (OMT) for uncomplicated type B aortic
      dissection (uTBAD) provides excellent short-term outcomes but is associated with
      a high incidence of failure. This study identified predictors of aortic
      intervention and mortality in uTBAD patients undergoing OMT. METHODS: A
      retrospective review of the Emory aortic database from 2000-2016 identified 314
      uTBAD patients undergoing OMT. Two hundred and sixty-three (84%) patients had
      imaging at presentation analyzed for maximum aortic diameters (AD), false lumen
      (FL) status, and visceral vessel perfusion. Cox proportional hazards models were
      constructed to estimate hazards ratios (HR) and identify predictors of OMT
      failure. RESULTS: The mean age of patients was 58+/-12 years, and 67% were male.
      FL status was patent in 59.4%, partially thrombosed in 39.8%, and completely
      thrombosed in 0.8% of patients. Over a median follow-up of 5.6 [IQR: 1.4-8.5]
      years, 44.9% of patients failed OMT and underwent intervention: n=58 open, n=83
      endovascular. The estimated incidence of OMT failure was 46%. Multivariate
      analysis identified the presence of diabetes, renal failure, DeBakey 3B
      dissection and a descending thoracic AD of >=4.5cm [HR: 1.39 (1.24, 1.56),
      p<0.001] to be independent predictors of failure of OMT. FL status or the
      distribution of visceral vessels arising from the FL did not predict OMT failure.
      CONCLUSIONS: There is a significant incidence of OMT failure in uTBAD patients. A
      descending thoracic AD of >=4.5cm at the time of diagnosis is an independent
      predictor of failure of OMT.

PMID- 30292843
TI  - Toll-Like Receptor-4 Is a Mediator of Proliferation in Esophageal Adenocarcinoma.
AB  - BACKGROUND: Chronic inflammation from reflux disease has been implicated as part
      of the development of esophageal adenocarcinoma. Toll-like receptors (TLRs), a
      component of the innate immune system, have been implicated in mediating
      hyperplasia and metaplasia in response to inflammatory stimuli. Increased TLR4 in
      human esophageal cancer has been correlated with its carcinogenesis. We
      hypothesized that TLR4 mediates proliferation of human esophageal adenocarcinoma
      cells. METHODS: Normal human esophageal (HET1A) and adenocarcinoma (OE33, FLO-1)
      cell lines were cultured using standard techniques. TLR4 was measured at baseline
      and in response to reflux stimuli. All cell lines were treated with the TLR4
      agonist lipopolysaccharide for 48 hours, and growth response was measured.
      Changes in myeloid differentiation primary response 88 (MyD88), tumor necrosis
      factor receptor associated factor 6 (TRAF6), and nuclear factor-kappaB (NF
      kappaB) activity were measured during lipopolysaccharide treatment. All cell
      lines had NF-kappaB inhibited, and growth rate response was measured. RESULTS:
      TLR4 was expressed in all cell lines, with increased baseline expression in
      adenocarcinoma cell lines (p < 0.05). Reflux stimuli increased TLR4 expression (p
      < 0.01) in normal esophageal cells. After treatment with lipopolysaccharide, all
      cell lines showed significant increases in proliferation (p < 0.05) due to the NF
      kappaB pathway, and their growth rate was reduced with NF-kappaB inhibition (p <
      0.05). CONCLUSIONS: TLR4 is consistently detectable in esophageal cell lines and
      most highly expressed in adenocarcinoma. TLR4 expression increases in an
      inflammatory model of reflux disease. TLR4 activation results in increased
      proliferation due to the TLR4-MyD88-TRAF6-NF-kappaB signaling pathway, and
      inhibition of NF-kappaB leads to decreased esophageal cell growth. These findings
      suggest TLR4 may be a target to suppress esophageal cancer growth.

PMID- 30292844
TI  - Feasibility and Outcomes of TAVI using the Left Axillary Artery as Primary Access
      Site.
AB  - BACKGROUND: The femoral artery is generally used as primary access for TAVI.
      However, peripheral artery disease often precludes femoral access. The purpose of
      this study was to describe clinical outcome of TAVI using the left axillary
      artery (LAA) as primary access site. METHODS: From December 2008 until June 2016,
      data on all consecutive patients treated with a Medtronic device via the LAA at
      our hospital were registered and outcome was prospectively collected according to
      the updated VARC-2 criteria. Mortality check was performed nationally. RESULTS:
      In total 362 patients were included (median age 80[76-84] years, logistic
      Euroscore 17+/-12%). Successful axillary access was achieved in 99%. Medtronic
      CoreValve(86%) and Evolut R(14%) (Medtronic, Minneapolis, Minnesota, USA) were
      implanted. Major vascular complications occurred in 5% of patients, 1% was LAA
      related. Life-threatening and major bleeding was observed in 2% and 10%,
      respectively. Additional complications were: new LBBB (30%), new permanent
      pacemaker (11%) and stroke (1%). There were 6(2%) procedural deaths and 19(5%)
      deaths within 30 days. One-year mortality rate was 19%. CONCLUSIONS: This is the
      first study reporting on outcome after TAVI using the LAA as default access. We
      conclude that it is highly feasible and safe with low rates of major vascular
      complications, bleeding and stroke.

PMID- 30292845
TI  - Valve Sparing Root Replacement Provides Excellent Mid-Term Outcomes for Bicuspid
      Valve Aortopathy.
AB  - BACKGROUND: Standard therapy for aortic root dilation in the setting of bicuspid
      aortic valves remains use of a composite valve conduit. The long-term durability
      of valve sparing root replacement (VSRR) in bicuspid aortopathy is presently
      unclear. In this study, the mid-term results of performing VSRR in the setting of
      a bicuspid valve was analyzed. METHODS: A single institutional database
      identified 280 patients who underwent VSRR from 2005-2016. Outcomes were analyzed
      in 60 consecutive patients undergoing a VSRR in the setting of a bicuspid aortic
      valve with aortic insufficiency (AI). Patients were followed prospectively and
      had annual echocardiograms. RESULTS: The average age in this series was 42+/-11
      years. Eighty percent were male and 33% had NYHA Class III-IV symptoms. More than
      2+ AI was present in 42% of patients preoperatively. The incidence of operative
      death, stroke, and renal failure was 0%. Mean follow-up was 39+/-30 months. At
      latest follow-up, 62% of patients had zero AI and 87% of patients had <1+ AI. At
      5 years, freedom from >2+ AI was 97% and freedom from AVR was 96%. Preoperative
      AI was not found to be a significant risk factor for postoperative >2+ AI
      (p=0.61) or AVR (p=0.61). CONCLUSIONS: VSRR can be safely and effectively
      performed in young patients with bicuspid valve anatomy regardless of degree of
      pre-operative AI. Valve function is durable and the incidence of valve-related
      complications is low. VSRR is an attractive and potentially superior option to
      conventional root replacement in appropriately selected patients with bicuspid
      aortopathy.

PMID- 30292846
TI  - Combining Cerebral Perfusion with Retrograde Inferior Vena Caval Perfusion for
      Aortic Arch Surgery.
AB  - Hypothermic circulatory arrest and selective cerebral perfusion are standard
      procedures during total arch replacement to treat acute type A aortic dissection.
      However, organ ischemia during anastomosis between the graft and descending aorta
      contribute to high risk of mortality and morbidity. Here we describe the
      combination of antegrade cerebral perfusion and retrograde inferior vena caval
      perfusion as a way to ensure continual perfusion of the brain, abdominal viscera
      and spinal cord during anastomosis and thereby improve outcomes of total arch
      replacement.

PMID- 30292847
TI  - Comparing Two Imaging Methods for Follow-up of Lung Cancer Treatment: A
      Randomized Pilot Study.
AB  - BACKGROUND: Scientific data on the image modality to be used in post-curative
      treatment surveillance of non-small-cell lung cancer patients are scarce. This
      prospective randomized pilot trial aimed to compare the performance of integrated
      18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT)
      and contrast-enhanced computed tomography (CE-CT).. METHODS: After termination of
      curative-intent treatment, patients were randomly assigned to either the PET-CT
      or the CE-CT group. Imaging procedures were performed every 6 months for 2 years.
      If suspicious radiologic findings were detected or patients became symptomatic, a
      diagnostic work-up was initiated. Sensitivity, specificity, and positive
      predictive value for detecting cancer recurrence were calculated for both imaging
      procedures. RESULTS: There were 96 patients enrolled in the study. In 14 of 50
      patients (28%) in the PET-CT group and in 14 of 46 patients (30%) in the CE-CT
      group, a suspicious radiologic finding was confirmed as cancer recurrence after
      diagnostic work-up. False positive findings were detected in 11 patients (22%) of
      the PET-CT and 8 patients (17%) of the CE-CT group. The sensitivity, specificity,
      and positive predictive value for detecting cancer recurrence were 0.88 (95% CI:
      0.62-0.98), 0.62 (0.42-0.79), and 0.56 (0.35-0.76) for PET-CT and 0.93 (0.68
      1.00), 0.72 (0.53-0.87), and 0.64 (0.41-0.83) for CE-CT, respectively.
      CONCLUSIONS: The results of our study suggest that PET-CT is not superior to CE
      CT in detecting cancer recurrence during 2 years following curative-intent
      treatment of non-small-cell lung cancer.

PMID- 30292848
TI  - SAMHD1 and the innate immune response to cytosolic DNA during DNA replication.
AB  - Cytosolic DNA of endogenous or exogenous origin is sensed by the cGAS-STING
      pathway to activate innate immune responses. Besides microbial DNA, this pathway
      detects self-DNA in the cytoplasm of damaged or abnormal cells and plays a
      central role in antitumor immunity. The mechanism by which cytosolic DNA
      accumulates under genotoxic stress conditions is currently unclear, but recent
      studies on factors mutated in the Aicardi-Goutieres syndrome cells, such as
      SAMHD1, RNase H2 and TREX1, are shedding new light on this key process. In
      particular, these studies indicate that the rupture of micronuclei and the
      release of ssDNA fragments during the processing of stalled replication forks and
      chromosome breaks represent potent inducers of the cGAS-STING pathway.

PMID- 30292849
TI  - Measurement of Multiple Solid Portions in Part-Solid Nodules for T
      Categorization: Evaluation of Prognostic Implication.
AB  - INTRODUCTION: Our study aimed to analyze the prognostic implication of the
      multiplicity of solid portions in part-solid nodules (PSNs) on computed
      tomography scans and compare the prognostic performance of various measures of
      solid portions, including the single largest solid portion, solid proportion, and
      summated multiple solid portion measurements. METHODS: The cases of a total of
      345 patients with surgically resected stage IA adenocarcinomas manifesting as
      PSNs were retrospectively reviewed. The multiplicity of the solid portion in PSNs
      was determined and the diameter of each solid portion was measured. The
      prognostic implication of the multiplicity of the solid portion and other
      clinical variables in relation to disease-free survival (DFS) was analyzed by
      using Cox regression. In addition, risk stratification based on the single
      largest solid portion, sum of the solid portions, single solid proportion, and
      sum of the solid proportions was conducted. Next, concordance indices (C-indices)
      for DFS were obtained for each measure and compared. Intrareader and interreader
      measurement variability was assessed. RESULTS: Multiplicity of the solid portion
      did not have a significant effect on DFS; clinical T category was the only
      independent risk factor for tumor recurrence (p < 0.05). The C-index of the
      single solid portion (conventional clinical T category) was 0.817 (95% confidence
      interval: 0.691-0.942). There were no significant differences (p > 0.05) between
      the C-indices of the single solid portion and other solid portion measures.
      Interreader measurement variability was substantial. CONCLUSIONS: The current
      clinical T categorization of PSNs based on the single solid portion measurement
      is appropriate.

PMID- 30292850
TI  - Prophylactic Cranial Irradiation for Limited-Stage Small-Cell Lung Cancer
      Patients: Secondary Findings From the Prospective Randomized Phase 3 CONVERT
      Trial.
AB  - INTRODUCTION: The impact of the dose and fractionation of thoracic radiotherapy
      on the risk of developing brain metastasis (BM) has not been evaluated
      prospectively in limited stage SCLC patients receiving prophylactic cerebral
      irradiation (PCI). METHODS: Data from patients treated with PCI from the CONVERT
      trial were analyzed. RESULTS: Four hundred forty-nine of 547 patients (82%)
      received PCI after completion of chemoradiotherapy. Baseline brain imaging
      consisted of computed tomographic scans in 356 of 449 patients (79%) and magnetic
      resonance imaging in 83 of 449 (18%) patients. PCI was delivered to 220 of 273
      participants (81%) in the twice-daily (BD) group and 229 of 270 in the once-daily
      (OD) group (85%; p = 0.49). Total median PCI dose was 25 Gy in both the BD and OD
      groups (p = 0.74). In patients who received PCI, 75 (17%) developed BM (35 [8%]
      in OD and 40 [9%] in BD) and 173 (39%) other extracranial progression. In the
      univariate analysis, gross tumor volume (GTV) was associated with an increased
      risk of BM (p = 0.007) or other radiological progression events (p = 0.006),
      whereas in a multivariate analysis both thoracic GTV (tGTV) and ECOG performance
      score (PS) were associated with either progression type. The median overall
      survival (OS) of patients treated with PCI was 29 months. In the univariate
      analysis of OS, PCI timing from end of chemotherapy, weight loss of more than
      10%, and tGTV were prognostic factors associated with OS. In the multivariate
      analysis, only tGTV was associated with OS. Delay between end of chemotherapy and
      PCI was not associated with OS. CONCLUSIONS: Patients receiving OD or BD thoracic
      radiotherapy have the same risk of developing BM. Larger tumors are associated
      with a higher risk of BM.

PMID- 30292851
TI  - Minimally Invasive Approaches Do Not Compromise Outcomes for Pneumonectomy: A
      Comparison Using the National Cancer Database.
AB  - INTRODUCTION: Minimally invasive approaches are increasingly being used for the
      conduct of complex surgical procedures. Whether the benefits of minimally
      invasive approaches compared to thoracotomy for sublobar and lobar lung resection
      for NSCLC are realized for patients undergoing pneumonectomy is not clear.
      METHODS: The National Cancer Database was queried for patients who underwent
      pneumonectomy for NSCLC from 2010 to 2014. Case data from patients who underwent
      resection by minimally invasive surgery (MIS) were compared with those from
      patients who received thoracotomy (open) in an intention-to-treat analysis.
      Associations between potential covariates and treatment were analyzed using the
      Pearson chi-square test for categorical variables and Wilcoxon rank sum test for
      continuous variables. Univariable and multivariable logistic models and
      proportional hazards model were used to assess the effect of surgical approach on
      30-day and 90-day mortality and overall survival. Relative prognosis was
      summarized using odds ratios and hazards ratios estimates and 95% confidence
      limits. RESULTS: A total of 4,938 patients underwent pneumonectomy during the
      study period, of which 755 (15.3%) were completed by MIS. No difference was noted
      in 30- and 90-day mortality rates for MIS compared to open approaches (6.8% and
      12.3% versus 6.7% and 11.9%, respectively; p = 0.9 and 0.86, respectively). Tumor
      histology and stage characteristics were similar between the two groups. The mean
      number of lymph nodes examined was higher in the MIS group compared to the open
      thoracotomy group (17.1 +/- 0.4 versus 16.1 +/- 0.2, p = 0.034). The conversion
      rate for the MIS cohort was 36.7%. Surgical approach was not associated with any
      difference in perioperative mortality with univariable or multivariable analysis.
      MIS was associated with improved overall survival on univariable analysis, but
      this was not evident with multivariable analysis. CONCLUSIONS: Pneumonectomy
      performed by minimally invasive approaches does not compromise perioperative
      mortality or long-term outcomes. Further investigation into the impact of
      minimally invasive approaches on perioperative outcomes for whole-lung resection
      is warranted.

PMID- 30292852
TI  - Toxicity Related to Radiotherapy Dose and Targeting Strategy: A Pooled Analysis
      of Cooperative Group Trials of Combined Modality Therapy for Locally Advanced Non
      Small Cell Lung Cancer.
AB  - OBJECTIVE: Concurrent chemoradiotherapy (CRT) was the standard treatment for
      locally advanced NSCLC (LA-NSCLC). This study was performed to examine thoracic
      radiotherapy (TRT) parameters and their impact on adverse events (AEs). METHODS:
      We collected individual patient data from 3600 patients with LA-NSCLC who
      participated in 16 cooperative group trials of concurrent CRT. The TRT parameters
      examined included field design strategy (elective nodal irradiation [ENI] versus
      involved-field [IF] TRT [IF-TRT]) and TRT dose (60 Gy versus >=60 Gy). The
      primary end point of this analysis was the occurrence of AEs. ORs for AEs were
      calculated with univariable and multivariable logistic models. RESULTS: TRT doses
      ranged from 60 to 74 Gy. ENI was not associated with more grade 3 or higher AEs
      than IF-TRT was (multivariable OR = 0.77, 95% confidence interval [CI]: 0.543
      1.102, p = 0.1545). Doses higher than 60 Gy (high-dose TRT) were associated with
      significantly more grade 3 or higher AEs (multivariable OR = 1.82, 95% CI: 1.501
      2.203, p < 0.0001). In contrast, ENI was associated with significantly more grade
      4 or higher AEs (multivariable OR = 1.33, 95% CI: 1.035-1.709, p = 0.0258). Doses
      higher than 60 Gy were also associated with more grade 4 or higher AEs
      (multivariate OR = 1.42, 95% CI: 1.191-1.700, p = 0.0001). Grade 5 AEs plus
      treatment-related deaths were more frequent with higher-dose TRT (p = 0.0012) but
      not ENI (p = 0.099). CONCLUSIONS: For patients with LA-NSCLC treated with
      concurrent CRT, IF-TRT was not associated with the overall risk of grade 3 or
      higher AEs but was associated with significantly fewer grade 4 or higher AEs than
      ENI TRT. This is likely the result of irradiation of a lesser amount of adjacent
      critical normal tissue. Higher TRT doses were associated significantly with grade
      3 or higher and grade 4 or higher AEs. On the basis of these findings and our
      prior report on survival, CRT using IF-TRT and 60 Gy (conventionally
      fractionated) were associated with more favorable patient survival and less
      toxicity than was the use of ENI or higher radiotherapy doses.

PMID- 30292853
TI  - Atlas of Axial Spondyloarthritis in Spain 2017: Study Design and Population.
AB  - OBJECTIVE: Atlas of Axial Spondyloarthritis in Spain 2017 aims to better
      understand the reality of the patients suffering from this disease from an
      integrated approach. METHODS: The Atlas 2017 based its results on an extensive
      cross-sectional patient survey conducted in Spain (2016), validated by a
      multidisciplinary group of experts on spondyloarthritis. RESULTS: Data from 680
      patients with axSpA were obtained, most of them suffered from AS, were HLA-B27
      positive, older than 45 years, and live as part of a couple. A large percentage
      had university studies, were disabled and members of a patient association.
      Patients reported a diagnostic delay of 8.5 years, high disease activity (BASDAI
      5.5+/-2.2), moderate-important stiffness (61.0%), medium-high functional
      limitation (74.9%), and psychological distress (GHQ 5.7+/-4.5). A total of 54.7%
      reported taking NSAIDs, 28.4% DMARDs, 36.3% biological therapy and 32.2% were not
      receiving pharmacological treatment. CONCLUSIONS: The Atlas survey data reveals
      still a long diagnostic delay, high disease activity, psychological distress,
      while an important proportion could be undertreated.

PMID- 30292854
TI  - Utilizing soft constraints to enhance medical relation extraction from the
      history of present illness in electronic medical records.
AB  - Relation extraction between medical concepts from electronic medical records has
      pervasive applications as well as significance. However, previous researches
      utilizing machine learning algorithms judge the semantic types of medical concept
      pair mentions independently. In fact, different concept pair mentions in the same
      context are of dependencies which can provide beneficial evidences for
      identifying their relation types. To the best of our knowledge, only one study
      has considered such dependencies in discharge summaries. However, its hard
      constraints are not applied effectively to the History of Present Illness (HPI)
      in electronic Medical Records. According to the writing characteristics of HPI
      records, we generalize two regularities of dependencies among concept pairs
      mentioned in an HPI record to enhance the performance of relation extraction. We
      incorporate the two soft constraints corresponding to the regularities and the
      posterior probabilities returned by a local classifier into a joint inference
      process which applies Integer Quadratic Programming method to carry out
      collective classification for all concept pair mentions in an HPI record. We
      implement four local classification models including support vector machine,
      logistics regression, random forest and piecewise convolutional neural networks
      to examine the performance of our approach. A series of experimental results
      demonstrate that our collective classification method has made a principal
      improvement and outperforms the other state-of-the-art methods.

PMID- 30292855
TI  - Social media mining for birth defects research: A rule-based, bootstrapping
      approach to collecting data for rare health-related events on Twitter.
AB  - BACKGROUND: Although birth defects are the leading cause of infant mortality in
      the United States, methods for observing human pregnancies with birth defect
      outcomes are limited. OBJECTIVE: The primary objectives of this study were (i) to
      assess whether rare health-related events-in this case, birth defects-are
      reported on social media, (ii) to design and deploy a natural language processing
      (NLP) approach for collecting such sparse data from social media, and (iii) to
      utilize the collected data to discover a cohort of women whose pregnancies with
      birth defect outcomes could be observed on social media for epidemiological
      analysis. METHODS: To assess whether birth defects are mentioned on social media,
      we mined 432 million tweets posted by 112,647 users who were automatically
      identified via their public announcements of pregnancy on Twitter. To retrieve
      tweets that mention birth defects, we developed a rule-based, bootstrapping
      approach, which relies on a lexicon, lexical variants generated from the lexicon
      entries, regular expressions, post-processing, and manual analysis guided by
      distributional properties. To identify users whose pregnancies with birth defect
      outcomes could be observed for epidemiological analysis, inclusion criteria were
      (i) tweets indicating that the user's child has a birth defect, and (ii)
      accessibility to the user's tweets during pregnancy. We conducted a semi
      automatic evaluation to estimate the recall of the tweet-collection approach, and
      performed a preliminary assessment of the prevalence of selected birth defects
      among the pregnancy cohort derived from Twitter. RESULTS: We manually annotated
      16,822 retrieved tweets, distinguishing tweets indicating that the user's child
      has a birth defect (true positives) from tweets that merely mention birth defects
      (false positives). Inter-annotator agreement was substantial: kappa = 0.79
      (Cohen's kappa). Analyzing the timelines of the 646 users whose tweets were true
      positives resulted in the discovery of 195 users that met the inclusion criteria.
      Congenital heart defects are the most common type of birth defect reported on
      Twitter, consistent with findings in the general population. Based on an
      evaluation of 4169 tweets retrieved using alternative text mining methods, the
      recall of the tweet-collection approach was 0.95. CONCLUSIONS: Our contributions
      include (i) evidence that rare health-related events are indeed reported on
      Twitter, (ii) a generalizable, systematic NLP approach for collecting sparse
      tweets, (iii) a semi-automatic method to identify undetected tweets (false
      negatives), and (iv) a collection of publicly available tweets by pregnant users
      with birth defect outcomes, which could be used for future epidemiological
      analysis. In future work, the annotated tweets could be used to train machine
      learning algorithms to automatically identify users reporting birth defect
      outcomes, enabling the large-scale use of social media mining as a complementary
      method for such epidemiological research.

PMID- 30292857
TI  - Testosterone, androstenedione and dehydroepiandrosterone concentrations in
      pregnant Spanish Purebred mare.
AB  - Androgens modulate maternal ovarian activity, embryo implantation and correct
      placental development. The objective of this study was to establish reference
      values for testosterone (T), androstenedione (A4) and dehydroepiandrosterone
      (DHEA) concentrations in pregnant mares. A total of 30 healthy Spanish Purebred
      mares with an age range of 9.33 +/- 3.31 years, were studied during the 11 months
      of gestation. T, A4 and DHEA concentrations were determined using EIA validated
      specifically for equines. T increased in the 2nd and 3rd month (P < 0.05),
      showing a plateau between the 4th and 6th month, decreased from the 7th to the
      9th month (P < 0.05) and increased in the 10th month (P < 0.05), reaching the
      maximum value in the last month of pregnancy (P < 0.05). A4 increased in the 2nd
      month (P < 0.05), reaching the maximum value in the 3rd month (P < 0.05),
      decreased in the 4th month, increasing in the 5th and 6th month (P < 0.05). From
      the 7th month the average values decreased until reaching the minimum at the end
      of gestation. DHEA progressively increased from the 1st to the 5th month, at
      which time the maximum mean value was reached (P < 0.05), after a decrease in the
      6th and 7th month occurred (P < 0.05), reaching the minimum value in the last
      month of gestation. T, A4 and DHEA were positive and significantly correlated (P
      < 0.05). The androgens analyzed in this study can be used as predictive markers
      of pregnancy in the mare.

PMID- 30292856
TI  - Differences in the thermal sensitivity and seminal quality of distinct ovine
      genotypes raised in tropical conditions.
AB  - For different ovine breeds to maximize their reproductive capacity in countries
      with tropical climate, it is important to evaluate their potential for thermal
      resilience and consequences on their reproductive traits. Therefore, the
      objective of this study was to evaluate the effect of thermal environment
      temperatures of climate seasons in a tropical climate region on the surface
      temperatures of the scrotum, testicular biometric characteristics, seminal
      quality and serum testosterone concentration of rams of different genotypes.
      Breeders of four different genotypes (Dorper, n = 8, Texel, n = 8, Santa Ines, n
      = 9 and Morada Nova, n = 8) were used throughout the four climate seasons. Higher
      thermal challenge was recorded in the spring and summer. In the summer increase
      in scrotal surface temperature was detected by infrared thermography (P < 0.05),
      mainly in the regions of the distal testicular pole and tail of the epididymis.
      The animals of the Texel genotype had higher rectal temperature in the summer. In
      spring, this genotype also had the highest testicular pole (32.2 +/- 0.5  degrees
      C; P < 0.05) and distal (29.9 +/- 0.4  degrees C; P < 0.05) temperatures and a
      higher mean testicular temperature (31.7 +/- 0.4  degrees C; P < 0.05). The
      Morada Nova genotype showed a higher surface temperature gradient between
      testicular poles (2.96 +/- 0.1  degrees C; P < 0.05), especially in spring.
      Genotype-dependent thermal sensitivity was detected for the thermal gradient
      between the testicular poles, reflecting the seminal quality. There was a
      positive correlation of the thermal gradient between testicular poles with sperm
      membrane integrity and negative correlation with total sperm defects. The Texel
      genotype showed less progressive motility and higher percentage of sperm defects.
      There was no difference in testosterone concentration between genotypes and in
      the different seasons (P > 0.05). Thus, the indigenous genotypes showed a greater
      capability to maintain the scrotum-testicular thermoregulation. Dorper animals
      resembled the indigenous sheep genotypes, in terms of seminal characteristics,
      unlike Texel animals, which showed lower adaptability and lower seminal quality.

PMID- 30292858
TI  - Monthly changes in testicular blood flow dynamics and their association with
      testicular volume, plasma steroid hormones profile and semen characteristics in
      rams.
AB  - The present detailed study aimed to establish for the first time reference values
      for ultrasound measures of testicular dimensions and Doppler measures of blood
      flow in the testicular artery of rams over a 12-month period, and to investigate
      a possible association between monthly changes in dynamics of testicular blood
      flow from one hand and testicular volume, plasma testosterone and estradiol 
      17beta concentrations as well as semen characteristics from the other hand. Five
      fat-tailed rams weighing 45-60 kg and aging 2-4 years old were subjected to semen
      collection, jugular blood sampling, ultrasonographic scanning of the testes and
      Doppler examination of testicular artery twice monthly for a period of one year.
      The overall mean (+/-SD) values for testicular volume as well as RI (resistive
      index) and PI (pulsatility index), respectively were 71.84 +/- 5.33 mm3, 0.378 +/
      0.102 and 0.642 +/- 0.208. Average testicular volume was the lowest in June
      (59.44 +/- 5.83 mm3) and reached its maximum (84.43 +/- 8.52 mm3) in November
      after 42.2% increase (p < 0.01). Mean values of RI were lowest between September
      and March, increasing significantly (p < 0.01) in April (+53%) reaching highest
      value in June (0.564 +/- 0.158). From the lowest value recorded in October
      through February, the average PI values increased significantly (p < 0.05) in
      March (+41%) to reach maximum value in July (0.940 +/- 0.368). In parallel with
      the substantial decrease in Doppler measurements, all parameters analyzed during
      the breeding season (October-March) were positively affected. In conclusion, the
      monthly definite changes in the studied parameters evidenced three novel
      findings: (1) plasma testosterone concentration, which increased significantly (p
      < 0.05) at late summer (August), was the potential initiator for resuming the
      breeding season in rams via triggering spermatogenic activity and maximum
      testicular volume during this period, (2) resulting values of testicular volume
      and testicular blood flow profiles all year round provide useful reference values
      for predicting testicular function in rams, (3) the marked increase in testicular
      blood flow volume, i.e. remarkable decrease in both RI and PI values, during the
      breeding season could be regulated by the marked increase in testicular volume
      and plasma estradiol -17beta levels during this period.

PMID- 30292859
TI  - Derivation of chicken primordial germ cells using an indirect Co-culture system.
AB  - Primordial germ cells (PGCs) are promising genetic resources for avian studies
      including modified animals. However, chicken PGCs are slow to proliferate and
      gradually lose germline competency after long-term culture, which hinders their
      application in avian biotechnology. Thus, we developed a robust method for the
      isolation and rapid propagation of PGCs using an indirect co-culture system. PGCs
      derived from a pair of embryonic chicken gonads were expanded to 1 * 106 within 2
      weeks, and no sex bias was observed in. These PGCs presented high capacity of
      germline transmission and produced donor-derived offspring after injection into
      the chicken embryos. This system allows the efficient gene-banking of chicken
      species and can facilitate the production of chickens bearing a desired phenotype
      via genomic editing.

PMID- 30292860
TI  - Estrous detection by continuous measurements of vaginal temperature and
      conductivity with supervised machine learning in cattle.
AB  - This study aimed to evaluate the effectiveness of estrous detection technique
      based on continuous measurements of vaginal temperature (VT) and conductivity
      (VC) with supervised machine learning in cattle. The VT and VC of 17 cows in tie
      stalls were measured using our developed wearable vaginal sensor from Day 11 (Day
      0 = ovulation day) to Day 11 of the subsequent estrous cycle at 15-min interval.
      After the maximum VT and VC were extracted hourly, their changes were expressed
      as residual VT (rVT = actual VT - mean VT for the same time on the previous 3
      days) and as VC ratio (VCr = actual VC/mean VC for the same time on Day 11-13),
      respectively, and were used for analysis. Trans-rectal ultrasonography was
      performed to monitor ovarian structure changes. The plasma concentrations of
      reproductive hormones (progesterone: P4, estradiol-17beta: E2, and LH) were
      measured in the experimental period. Standing estrus was confirmed by testing
      with herd mates at 3-h interval. The rVT decreased transiently, which coincided
      with decreasing P4 a few days before estrus, and a sharp increase was associated
      with LH surge during estrus. The VCr increased as estrus approached,
      corresponding with decreasing P4 and increasing E2 and LH. After noise reduction,
      features, possible to follow-up estrus-associated changes in rVT and VCr, were
      extracted and used for developing estrous detection models; 9 models were
      developed with 3 feature sets (features extracted from rVT alone, VCr alone, and
      combination of rVT and VCr) and 3 machine learning algorithms (decision tree: DT,
      support vector machine: SVM, and artificial neural network: ANN). Cross
      validation showed that models using the features from the combination of rVT and
      VCr showed better performance in terms of sensitivity and precision than those
      using features from VCr alone, and precision than those of using features from
      rVT alone. Within the models using the features from the combination of rVT and
      VCr, sensitivity and precision of the model generated by ANN were numerically,
      but not statistically, higher than those generated by DT and SVM. Of 17 estruses,
      16 were detected, with one false positive, when the best model was used.
      Furthermore, both mean and variance of the interval from the beginning of the
      estrous detection alert to ovulation (27.3 +/- 6.7 h, mean +/- SD of 16 estruses)
      were not significantly different to those from the onset of standing estrus to
      ovulation (30.8 +/- 5.8 h, n = 17), indicating that the estrus can be detected
      real-time by the present technique. Hence, the estrous detection technique based
      on continuous measurements of VT and VC with supervised machine learning has a
      potential for efficient and accurate estrous detection in cattle.

PMID- 30292861
TI  - A novel tool to evaluate the implant position and predict defibrillation success
      of the subcutaneous implantable cardioverter-defibrillator: The PRAETORIAN score.
AB  - BACKGROUND: Suboptimal positioning of the subcutaneous implantable cardioverter
      defibrillator (S-ICD) increases the defibrillation threshold and risk of
      conversion failure. OBJECTIVE: Our objective is to develop a tool to evaluate the
      implant position and predict defibrillation success of the S-ICD: the PRAETORIAN
      score. METHODS: The PRAETORIAN score is based on clinical and computer modeling
      knowledge of determinants affecting the defibrillation threshold: subcoil fat,
      subgenerator fat, and anterior positioning of the S-ICD generator. The score
      evaluates these determinants on the postoperative anterior-posterior and lateral
      chest radiographs and has 3 categories: 30-<90 points representing a low risk, 90
      <150 points representing an intermediate risk, and >=150 points representing a
      high risk of conversion failure. The score was developed using 2 separate S-ICD
      data sets for derivation and validation. The performance metrics are the positive
      and negative predictive values. RESULTS: The development data set consisted of
      181 patients with S-ICD, and the validation cohort consisted of 321 patients from
      the S-ICD Investigational Device Exemption trial. The distribution of scores was
      93%-98% low risk (<90 points), 2%-5% intermediate risk (90-<150 points), and 1%
      high risk (>=150 points). The positive predictive value for an intermediate or
      high PRAETORIAN score for a failed conversion test was 51%, while a low
      PRAETORIAN score predicted a successful conversion in 99.8% of patients.
      CONCLUSION: The PRAETORIAN score allows the identification of patients with high
      defibrillation thresholds by using the routine chest radiograph and provides
      feedback to implanters on S-ICD positioning. The PRAETORIAN-DFT trial will
      prospectively validate the score by randomizing to standard conversion testing vs
      using the score without conversion testing.

PMID- 30292862
TI  - Three-dimensional reconstruction and quantification of dislocation substructures
      from transmission electron microscopy stereo pairs.
AB  - A great amount of material properties is strongly influenced by dislocations, the
      carriers of plastic deformation. It is therefore paramount to have appropriate
      tools to quantify dislocation substructures with regard to their features, e.g.,
      dislocation density, Burgers vectors or line direction. While the transmission
      electron microscope (TEM) has been the most widely-used equipment implemented to
      investigate dislocations, it usually is limited to the two-dimensional (2D)
      observation of three-dimensional (3D) structures. We reconstruct, visualize and
      quantify 3D dislocation substructure models from only two TEM images (stereo
      pairs) and assess the results. The reconstruction is based on the manual
      interactive tracing of filiform objects on both images of the stereo pair. The
      reconstruction and quantification method are demonstrated on dark field (DF)
      scanning (S)TEM micrographs of dislocation substructures imaged under diffraction
      contrast conditions. For this purpose, thick regions (>300 nm) of TEM foils are
      analyzed, which are extracted from a Ni-base superalloy single crystal after high
      temperature creep deformation. It is shown how the method allows 3D
      quantification from stereo pairs in a wide range of tilt conditions, achieving
      line length and orientation uncertainties of 3% and 7 degrees , respectively.
      Parameters that affect the quality of such reconstructions are discussed.

PMID- 30292863
TI  - Bacterial replisomes.
AB  - Bacterial replisomes are dynamic multiprotein DNA replication machines that are
      inherently difficult for structural studies. However, breakthroughs continue to
      come. The structures of Escherichia coli DNA polymerase III (core)-clamp-DNA
      subcomplexes solved by single-particle cryo-electron microscopy in both
      polymerization and proofreading modes and the discovery of the stochastic nature
      of the bacterial replisomes represent notable progress. The structures reveal an
      intricate interaction network in the polymerase-clamp subassembly, providing
      insights on how replisomes may work. Meantime, ensemble and single-molecule
      functional assays and fluorescence microscopy show that the bacterial replisomes
      can work in a decoupled and uncoordinated way, with polymerases quickly
      exchanging and both leading-strand and lagging-strand polymerases and the
      helicase working independently, contradictory to the elegant textbook view of a
      highly coordinated machine.

PMID- 30292864
TI  - Use of Virtual Surgical Planning and Virtual Dataset With Intraoperative
      Navigation to Guide Revision of Complex Facial Fractures: A Case Report.
AB  - The use of intraoperative navigation has become prevalent in multiple surgical
      fields, including neurosurgery, orthopedic surgery, spine surgery, and head and
      neck surgery. In the past decade, its use also has become popular in oral and
      maxillofacial surgery. Previous studies have suggested the use of intraoperative
      navigation improves surgical precision and accuracy and decreases intraoperative
      risks and postsurgical morbidity. This report presents a case in which
      intraoperative navigation was used for revision and secondary reconstruction of
      multiple facial fractures. Preoperative virtual surgical planning allowed
      customization of osteotomies of multiple bony segments and virtual reduction of
      these segments to their anatomically correct position. Then, the newly
      reconstructed 3-dimensional virtual computed tomographic dataset was used as a
      template in the navigation system to guide the osteotomies and precisely
      reposition bony fragments during surgery. This report describes the workflow
      necessary to use this technology.

PMID- 30292865
TI  - Before-after safety analysis using extreme value theory: A case of left-turn bay
      extension.
AB  - There is growing interest in the use of traffic conflicts in before and after
      safety evaluations because of well-recognized quality and quantity problems
      associated with historical crash records. Most of these studies apply statistical
      techniques to compare the number of conflicts before and after the implementation
      of safety countermeasures. However, to identify the number of conflicts, a
      specific threshold for various conflict indicators needs to be used and the
      results of the evaluation can vary significantly depending on the selection of
      this threshold. As well, there is an issue with how to account for conflict
      severity in the evaluation. This study proposes adopting the extreme value theory
      approach to overcome these two issues. The approach was applied to a case of left
      turn bay extension at three signalized intersections, and the automated traffic
      conflict technique was used to identify conflicts with TTC values from the video
      data collected from treatment sites and matching control sites. Generalized
      extreme value (GEV) models with different covariates were developed and compared.
      The results show that there are apparent shape change in the GEV distribution
      (i.e., from narrow peak up to high severities to wide spread with fewer conflicts
      at high severity levels) after the treatment, indicating reduction in conflict
      severity. The safety improvement is further confirmed by the total reduction of
      63.9% in estimated crashes. Moreover, with the aid of GEV model, the most severe
      conflicts that are also rare and random are included into the OR calculation, and
      a significant reduction of 73.2% is found in the estimated most severe conflicts.

PMID- 30292866
TI  - Gaze doesn't always lead steering.
AB  - In car driving, gaze typically leads the steering when negotiating curves. The
      aim of the current study was to investigate whether drivers also use this gaze
      leads-steering strategy when time-sharing between driving and a visual secondary
      task. Fourteen participants drove an instrumented car along a motorway while
      performing a secondary task: looking at a specified visual target as long and as
      much as they felt it was safe to do so. They made six trips, and in each trip the
      target was at a different location relative to the road ahead. They were free to
      glance back at the road at any time. Gaze behaviour was measured with an eye
      tracker, and steering corrections were recorded from the vehicle's CAN bus. Both
      in-car 'Fixation' targets and outside 'Pursuit' targets were used. Drivers often
      used a gaze-leads-steering strategy, glancing at the road ahead 200-600 ms before
      executing steering corrections. However, when the targets were less eccentric
      (requiring a smaller change in glance direction relative to the road ahead), the
      reverse strategy, in which glances to the road ahead followed steering
      corrections with 0-400 ms latency, was clearly present. The observed use of
      strategies can be interpreted in terms of predictive processing: The gaze-leads
      steering strategy is driven by the need to update the visual information and is
      therefore modulated by the quality/quantity of peripheral information.
      Implications for steering models are discussed.

PMID- 30292867
TI  - Seatbelt wearing rate in a Chinese city: Results from multi-round cross-sectional
      studies.
AB  - OBJECTIVE: Road traffic crashes impose a heavy burden in China's most populous
      city, Shanghai. Since early 2016, Shanghai police have started deploying high
      resolution cameras and an object-detection algorithm in seatbelt enforcement.
      Around the same time, an international consortium on road safety launched a
      series of capacity trainings for law enforcement accompanied by infrastructure
      renovation and social marketing campaigns in Shanghai. Our objective is to assess
      the level and trend of seatbelt use in Shanghai over 2015-2017. METHODS: Ongoing
      observational studies evaluate seatbelt use within the city. Data are collected
      at eight randomly selected locations throughout the city, stratified by road type
      and geographic locations. Data collection covers most times of the day on both
      business days and weekends, providing a full representation of varying traffic
      models during both rush hours and non-rush hours. At each site, trained field
      workers observe seatbelt use of occupants in all passing motorized vehicles. A
      multivariate logistic regression model was developed to analyze the data.
      FINDINGS: From October 2015 to December 2017, six rounds of data collection were
      completed with a total sample size of 77,641 drivers and passengers of motor
      vehicles. The seatbelt use rate has steadily increased over time, from 60.8% (95%
      CI: 59.9%-61.7%) in round 1 to 84.9% (84.3%-85.4%) in round 6 (p-value < 0.01).
      The increase is substantial and statistically significant for both drivers and
      passengers (p-value < 0.01). Results from the multivariate logistic regression
      show an annual growth rate of seatbelt use of 8.8% (8.4%-9.1%); the wearing rate
      was 49.8% (49.0%-50.5%) lower among passengers than drivers; 3.5% (2.9%-4.1%)
      lower in peri-urban areas than central urban areas; 16.3% (14.3%-18.4%) higher
      among 18-24-year and 18.9% (17.0%-20.9%) higher among 25-59-year olds than other
      age groups. CONCLUSION AND POLICY IMPLICATIONS: Seatbelt use in Shanghai has been
      boosted during a short period of time through a combined strategy that includes
      training of police, social marketing campaign, and the deployment of computer
      vision assisted enforcement. Large cities in China and other countries facing
      similar challenges with seatbelt wearing may learn from Shanghai's experience.

PMID- 30292868
TI  - Bayesian approach to model pedestrian crashes at signalized intersections with
      measurement errors in exposure.
AB  - This study intended to identify the potential factors contributing to the
      occurrence of pedestrian crashes at signalized intersections in a densely
      populated city, based on a comprehensive dataset of 898 pedestrian crashes at 262
      signalized intersections during 2010-2012 in Hong Kong. The detailed geometric
      design, traffic characteristics, signal control, built environment, along with
      the vehicle and pedestrian volumes were elaborately collected. A Bayesian
      measurement errors model was introduced as an alternative method to explicitly
      account for the uncertainties in volume data. To highlight the role played by
      exposure, models with and without pedestrian volume were estimated and compared.
      The results indicated that the omission of pedestrian volume in pedestrian crash
      frequency models would lead to reduced goodness-of-fit, biased parameter
      estimates, and incorrect inferences. Our empirical analysis demonstrated the
      existence of moderate uncertainties in pedestrian and vehicle volumes. Six
      variables were found to have a significant association with the number of
      pedestrian crashes at signalized intersections. The number of crossing
      pedestrians, the number of passing vehicles, the presence of curb parking, and
      the presence of ground-floor shops were positively related with pedestrian crash
      frequency, whereas the presence of playgrounds near intersections had a negative
      effect on pedestrian crash occurrences. Specifically, the presence of exclusive
      pedestrian signals for all crosswalks was found to significantly reduce the risk
      of pedestrian crashes by 43%. The present study is expected to shed more light on
      a deeper understanding of the environmental determinants of pedestrian crashes.

PMID- 30292869
TI  - Target-mimicry based diminution of miRNA167 reinforced flowering-time phenotypes
      in tobacco via spatial-transcriptional biases of flowering-associated miRNAs.
AB  - Evolutionarily conserved microRNAs such as miR156, miR159, miR167 and miR172
      tightly regulate the extensive array of gene expression during flowering in
      plants, through instant and long-term alterations in the expression of their
      target genes. Here we employed a novel target-mimicry approach for the diminution
      of auxin signalling regulator miRNA167 by developing mimic-transgenic lines in
      tobacco, to investigate the transcriptional biases of flowering-associated miRNAs
      in apical and floral meristematic tissues and their phenotypic implications.
      Recorded morpho-alterations such as uneven flowering-time phenotypes, anomalous
      floral organ formation, and large variations in the seed forming characteristics
      permitted us to determine the consequence of the extent of miR167 expression
      diminution accompanying the transcriptional biases of interrelated miRNAs. We
      demonstrate that percent diminution of miR167 gene expression is proportionally
      associated with both early and late flowering-time phenotypes in mimic lines.
      Also, the associated miRNAs, miR156, miR159, and miR172 showed >90%
      transcriptional diminution in at least 'early-flowering' miR167 mimic lines. On
      contrary, low percentages of their respective diminution were recorded in 'late
      flowering' lines. Evidently, the misexpression of miR156, miR159, and miR172 led
      to the over-expression of their respective target genes SPL9, AtMYB33-like and
      AP2 genes in mimic lines which resulted in assorted phenotypes. We describe the
      scope of spatial regulation of these microRNAs in floral bud tissues of mimic
      lines which showed negative- or very low (<25%) misexpression levels in
      early/late-flowering lines highlighting their roles in the acquisition of
      flowering mechanism. To our knowledge, this study represents the first
      characterization of transcriptional biases of flowering associated miRNAs in
      miR167-mimic lines and certainly augments our understanding of the importance of
      microRNA-mediated regulation of flowering in plants.

PMID- 30292870
TI  - Molecular cloning, characterization and expression analysis of ARMC6, ARMC7,
      ARMC8 from Pacific white shrimp, Litopenaeus vannamei.
AB  - Armadillo repeat-containing proteins (ARMCs) comprise a large family that is
      widely distributed in eukaryotes and plays prominent roles in cell-cell adhesion,
      intracellular signaling, and cytoskeletal regulation. In this study, three ARMC
      genes, termed LvARMC6, LvARMC7 and LvARMC8, were identified and characterized
      from Litopenaeus vannamei. The complete cDNAs open reading frames (ORF) of
      LvARMC6, LvARMC7, and LvARMC8 (GenBank accession no. MG735126, MG728109 and
      KX058562) were 1410 bp, 570 bp and 2046 bp, encoding 469, 189, and 681 amino
      acids, respectively. Topology analysis indicated that three ARM domains were
      present in LvARMC6, one in LvARMC7 and six in LvARMC8. The identities of all the
      three LvARMCs with other species were between 50% and 71%. Phylogenetic analysis
      illustrated that different subtype of ARMCs formed their own separate branches
      and LvARMCs were placed in branch of invertebrates respectively with strong
      bootstrap support. The constitutive expressions of LvARMCs were confirmed by real
      time quantitative PCR. LvARMC6, LvARMC7 and LvARMC8 were expressed highest in
      heart, gills and epithelium, respectively. After challenge with either white spot
      syndrome virus (WSSV), Vibrio parahemolyticus, or Staphylococcus aureus, all of
      the LvARMCs demonstrated differential expression profiles in hemocytes,
      hepatopancreas, intestine and gills. Taken together, our results suggest that
      LvARMCs may play a role in the innate immune defense against pathogenic viral and
      bacterial infections of L. vannamei.

PMID- 30292871
TI  - Clinical significance of aberrant cyclin-dependent kinase-like 2 methylation in
      hepatocellular carcinoma.
AB  - BACKGROUND AND AIMS: Aberrant DNA methylation of cyclin-dependent kinase-like 2
      (CDKL2) had been observed in several types of tumors. Herein, the present study
      was aimed to explore the epigenetic and expression status of CDKL2 and evaluate
      the diagnostic potential of CDKL2 methylation in hepatocellular carcinoma (HCC).
      METHODS: The methylation status of CDKL2 was detected by methylation-sensitive
      restriction enzyme based quantitative PCR (MSRE-qPCR) and bisulfite genomic
      sequencing (BGS). The mRNA expression of CDKL2 was measured using real-time
      quantitative PCR (qPCR). The correlations between the methylation of CDKL2 and
      mRNA expression, clinicopathological features were evaluated. RESULTS: Compared
      with normal liver tissues, the methylation levels of CDKL2 were significantly
      increased in the HCC tissues and cell lines (All p < 0.05). And the receiver
      operating characteristic (ROC) analysis showed that the hypermethylation of CDKL2
      had a high specificity and sensitivity to distinguish adjacent non-tumor tissues
      from HCC tissues. Additionally, the mRNA expression levels of CDKL2 were
      decreased both in HCC tissues and cell lines than those in normal liver tissues
      (All p < 0.05), and the expression could be upregulated by 5-aza-2'-deoxycytidine
      treatment in HCC cell lines. Furthermore, the methylation of CDKL2 was negatively
      correlated with its mRNA expression (p < 0.001, rs = -0.513), and was associated
      with gender (p = 0.023), age (p = 0.001) and tumor size (p = 0.016). CONCLUSIONS:
      Our results showed that CDKL2 promoter hypermethylation played an important role
      in hepatocarcinogenesis and might be a valuable biomarker for HCC diagnosis.

PMID- 30292872
TI  - Dual functions of microglia in the formation and refinement of neural circuits
      during development.
AB  - Microglia colonize the central nervous system (CNS) parenchyma during
      embryogenesis and contribute to various developmental processes leading to the
      formation of refined neural circuits. In this review, we focus on the
      bidirectional function of microglia during normal CNS development and discuss
      recent perspectives on the functions of microglia in neural circuit formation.
      Microglia participate in neurogenesis, migration, axonal growth, and synapse
      formation and remodeling, all of which are fundamental for the establishment of
      neural networks, by secreting a variety of molecules toward neurons and
      phagocytosing both live and dying neurons or their debris. Intriguingly,
      microglia play dual roles in each of the neurodevelopmental processes that they
      affect. For instance, microglia modulate synapse numbers by both promoting the
      formation of new synapses and eliminating unnecessary synapses. The study of the
      developmental roles of microglia is essential not only for understanding normal
      CNS development but also for preventing developmental brain disorders caused by
      microglial dysfunction.

PMID- 30292873
TI  - Effect of harvest timing on the dynamics of the Ricker-Seno model.
AB  - The moment of intervention is a key question in harvest programmes and is
      currently generating an increasing interest. However, little is known about its
      effect on the population stability. This lack of knowledge is greater in the case
      of global stability, which is always desirable as it allows to predict the fate
      of populations regardless of the initial size. Here we use a discrete-time
      equation to model the dynamics of populations harvested at any time during the
      reproductive season. We study the effect of the time of intervention on the
      global stability of populations governed by the Ricker model, which is one of the
      most relevant models in discrete-time population dynamics. We prove that harvest
      timing never has a negative effect on the global stability of these populations,
      extending recent results in the literature. We also study the effect of delayed
      harvesting on the constancy stability of the controlled populations.

PMID- 30292874
TI  - Asymptotic stability of delayed consumer age-structured population models with an
      Allee effect.
AB  - In this article we study a nonlinear age-structured consumer population model
      with density-dependent death and fertility rates, and time delays that model
      incubation/gestation period. Density dependence we consider combines both
      positive effects at low population numbers (i.e., the Allee effect) and negative
      effects at high population numbers due to intra-specific competition of
      consumers. The positive density-dependence is either due to an increase in the
      birth rate, or due to a decrease in the mortality rate at low population numbers.
      We prove that similarly to unstructured models, the Allee effect leads to model
      multi-stability where, besides the locally stable extinction equilibrium, there
      are up to two positive equilibria. Calculating derivatives of the basic
      reproduction number at the equilibria we prove that the upper of the two non
      trivial equilibria (when it exists) is locally asymptotically stable
      independently of the time delay. The smaller of the two equilibria is always
      unstable. Using numerical simulations we analyze topologically nonequivalent
      phase portraits of the model.

PMID- 30292875
TI  - The effect of affordable daycare on women's mental health: Evidence from a
      cluster randomized trial in rural India.
AB  - Access to affordable daycare might improve population mental health. However,
      evidence is sparse and restricted to middle- and high-income country settings. We
      conducted a cluster-randomized controlled trial in one low-income setting, rural
      Rajasthan, India. Communities lacking daycare facilities were identified (n =
      160) and randomly selected for assistance in setting up a community-based daycare
      program (n = 80) or not (n = 80). Women eligible for the daycare program living
      in these communities completed structured interviews before the intervention
      (participation rate = 89%) and approximately one year after rollout of the
      intervention (participation rate = 96%), resulting in a final analytic sample of
      3041. Mental distress was measured with the Hindi version of the 12-item General
      Health Questionnaire (score range: 0-12). We modeled the relation between access
      to daycare and number of mental distress symptoms (GHQ-12 score) with negative
      binomial regression using an intention-to-treat approach, which groups women
      according to if they lived in communities randomized to affordable daycare. We
      also evaluated the effect of access to daycare on secondary outcomes that may be
      related to mental distress, including women's work burden, agency, and intimate
      partner violence (IPV). We found that access to daycare resulted in modest
      reductions in symptoms of mental distress (mean difference = 0.21, 95% CI: -0.43,
      0.02). We found some evidence that daycare reduced IPV, but virtually no change
      in women's work burden or agency. Our results provide some indication that access
      to affordable daycare might be one policy lever to improve population mental
      health.

PMID- 30292876
TI  - Neighborhood effects on body mass: Temporal and spatial dimensions.
AB  - Research examining the effects of neighborhood characteristics on obesity and
      excess body weight has generally neglected the influence of both life-course
      exposure and geographically-proximate communities. Using data on 9357 respondents
      to the National Longitudinal Survey of Youth, 1979 Cohort, in conjunction with
      tract-level data from the 1980-2010 U.S. censuses, this study examines how black,
      Hispanic, and white individuals' cumulative exposure to varying levels of
      neighborhood poverty and co-ethnic density from their mid-teens through mid
      adulthood, as well as the levels of poverty and co-ethnic density in nearby, or
      "extralocal," neighborhoods, are associated with their body mass index (BMI).
      Fixed-effect regression models show that, among Hispanics and whites, cumulative
      exposure to co-ethnic neighbors is a stronger positive predictor of BMI than the
      co-ethnic density of the immediate, point-in-time neighborhood. Among whites,
      cumulative exposure to neighborhood poverty is a stronger positive predictor of
      BMI than is the poverty rate of the current neighborhood of residence. And among
      both blacks and whites, the distance-weighted poverty rate of extralocal
      neighborhoods is significantly and inversely related to BMI, suggesting that
      relative affluence in nearby neighborhoods engenders relative deprivation among
      residents of the focal neighborhood, leading to increased BMI. Overall, the
      results suggest that greater attention to both the temporal and spatial
      dimensions of neighborhood effects has the potential to enhance our understanding
      of how neighborhoods affect obesity and related health outcomes.

PMID- 30292877
TI  - Production of bioactive cyclotides in somatic embryos of Viola odorata.
AB  - Viola odorata L. (Violaceae), an Indian medicinal plant, contains a plethora of
      cyclotides, which are a class of cyclic peptides derived from plants, possessing
      several applications. Somatic embryo culture of V. odorata was developed, via
      indirect somatic embryogenesis, to serve as an alternative to natural plant
      biomass for sustainable and continuous production of its bioactive ingredients,
      such as cyclotides. Among the various combinations of phytohormones tested,
      Murashige and Skoog medium supplemented with 1 mg/l thidiazuron gave rise to the
      maximum frequency of induction (86.7%) and a high number of somatic embryos (3)
      from an embryogenic callus. Identification and characterization of cyclotides in
      the somatic embryos were carried out using a Fourier transform mass spectrometer
      coupled with liquid chromatography (LC-FTMS). Among the cyclotides identified in
      the study, few were found to be exclusively present in the somatic embryo
      culture. Furthermore, the relative abundance of the cyclotides was higher in
      somatic embryo extract than in the natural plant extract. The biological
      activities (cytotoxic, haemolytic and antimicrobial) of the somatic embryos and
      the parent plant were compared. Unlike the natural plants, the somatic embryo
      extracts demonstrated specificity i.e. they were found to be potent against
      cancerous cells but not against non-cancerous cell line or red blood cells. In
      contrast to the plant extract, the somatic embryos extracts were found to be
      potent against Escherichia coli and Staphylococcus aureus. These results suggest
      that somatic embryos of V. odorata (rich in cyclotides) can be used as an
      alternative to plant biomass for its therapeutic applications and germplasm
      conservation.

PMID- 30292878
TI  - Job satisfaction among critical care nurses: A systematic review.
AB  - BACKGROUND: Nursing shortages, particularly in critical care units, are a major
      concern worldwide. Job satisfaction is a key factor associated with the high
      turnover of critical care nurses. OBJECTIVES: The purpose of this systematic
      review was to synthesize the evidence on critical care nurses' job satisfaction.
      Specific research questions were: 1. How is job satisfaction defined and measured
      in studies of critical care nurses? 2a. What is the level of job satisfaction
      among critical care nurses? 2b. How has it changed over time? 2c. Do nurses'
      levels of job satisfaction differ by type of critical care unit? 3. What factors
      are associated with critical care nurses' job satisfaction? DESIGN: Systematic
      review. DATA SOURCES: We searched five electronic databases from January 1980 to
      May 2015: MEDLINE, CINAHL, PsychINFO, EMBASE, and Proquest Nursing & Allied
      Health Source. REVIEW METHODS: Two team members independently screened all titles
      and abstracts and extracted data and assessed methodological quality on all
      included papers. A narrative synthesis with vote counting was undertaken.
      RESULTS: A total of 1995 titles were identified, of which 61 satisfied our
      inclusion criteria. Only 24 (39%) of the included studies reported a conceptual
      definition of job satisfaction. Forty-two different quantitative measures of job
      satisfaction were identified, of which only 10 (24%) were used in multiple
      studies. The weighted mean job satisfaction score for critical care nurses across
      all studies was 56% satisfied and demonstrated fluctuations over time. Four
      factors showed significant positive relationships to job satisfaction: 1. shift
      worked - rotating 8- to 12-h and rotating days, evenings or nights; 2. Autonomy;
      3. personnel resources and staffing; and 4. teamwork and cohesion; while two
      factors showed significant negative relationships to job satisfaction: 1. job
      stress; and 2. burnout-emotional exhaustion. CONCLUSION: From this review, we did
      not find any evidence to support relationships between individual (socio
      demographic) factors and critical care nurses' job satisfaction. We did however
      find evidence to support relationships between several employment and
      organizational factors and job satisfaction. Several of these factors are
      different from those reported among general hospital nurses and long-term care
      nursing staff, supporting the need for differential strategies to improve
      critical care nurses' job satisfaction. While the findings from this review hold
      promise as potential targets of future job satisfaction interventions, there were
      several methodological problems inherent in many of the studies.

PMID- 30292879
TI  - Tumor necrosis factor receptor superfamily members 1a and 1b contribute to
      exacerbation of atherosclerosis by Chlamydia pneumoniae in mice.
AB  - The host immune responses that mediate Chlamydia-induced chronic disease sequelae
      are incompletely understood. The role of TNF-alpha, TNF receptor 1 (TNFR1), and
      TNF receptor 2 (TNFR2), in Chlamydia pneumoniae (CPN)-induced atherosclerosis was
      studied using the high-fat diet-fed male C57BL/6J mouse model. Following
      intranasal CPN infection, TNF-alpha knockout (KO), TNFR1 KO, TNFR2 KO, and TNFR
      1/2 double-knockout, displayed comparable serum anti-chlamydial antibody
      response, splenic antigen-specific cytokine response, and serum cholesterol
      profiles compared to wild type (WT) animals. However, atherosclerotic pathology
      in each CPN-infected KO mouse group was reduced significantly compared to WT
      mice, suggesting that both TNFR1 and TNFR2 promote CPN-induced atherosclerosis.

PMID- 30292880
TI  - Relationship between genome packaging and Gag translation/AUG of primate
      lentiviruses.
AB  - About the relationship between retroviral genome packaging and translation, three
      possible modes (random-, trans-, and cis-) of packaging process could be assumed.
      In this report, we developed an assay system based on the RT-qPCR to measure the
      packaging efficiency of primate lentiviruses. With this system, we analyzed the
      genome packaging modes of primate lentiviruses such as HIV-1, 2, SIVmac and
      SIVagm. The data suggested that the modes of all viruses analyzed were very
      similar. In addition, we observed that the Gag-AUG sequences of them played
      important roles for maintaining efficient packaging, other than the initiation of
      translation.

PMID- 30292881
TI  - Generation of CSi001-A, a transgene-free, induced pluripotent stem cell line
      derived from a Parkinson Disease (PD) patient.
AB  - Peripheral blood mononuclear cells (PBMC) were collected from a 70-year old
      Parkinson Disease patient. The PBMCs were reprogrammed with the human OKSM
      transcription factors using the non-integrating episomal vector system. The
      transgene-free iPSC showed pluripotency verified by immunocytochemistry for
      pluripotency markers and differentiated directly toward the 3 germ layers in
      vitro. Furthermore, the iPSC line showed normal karyotype.

PMID- 30292882
TI  - Generation of an induced pluripotent stem cell (iPSC) line from a patient with
      developmental and epileptic encephalopathy carrying a KCNA2 (p.Leu328Val)
      mutation.
AB  - Mutations in the KCNA2 gene, coding for the voltage-gated K+ channel Kv1.2, can
      cause developmental and epileptic encephalopathies. Kv1.2 channels play an
      important role in the repolarization phase of an action potential in nerve cells.
      Here, we reprogrammed human skin fibroblasts from a 13-year-old male patient with
      developmental and epileptic encephalopathy carrying a point mutation (c.982T>G,
      p.Leu328Val) in KCNA2 to human induced pluripotent stem cells (iPSCs) (HIHDNEi001
      A). The cells maintained a normal karyotype and their pluripotency state was
      verified by the expression and staining of several pluripotency markers and
      capability to differentiate into all three germ layers.

PMID- 30292883
TI  - Urine collection methods for non-toilet-trained children in biological monitoring
      studies: Validation of a disposable diaper for characterization of tebuconazole
      exposure.
AB  - Young children differ from adults in their exposure and susceptibility to
      environmental chemicals (e.g. pesticides) because of various factors such as
      behavior, diet and physiology. Their heightened vulnerability to environmental
      stressors makes it important to obtain appropriate urine samples for exposure
      characterization. However, collecting urine from non-toilet-trained children has
      been shown to be methodologically and practically challenging. Four urine
      collection approaches were tested: a disposable diaper, a urine bag, a collection
      pad and the clean catch. The success rate and the user rating of each method was
      evaluated. The success rates were 67%, 21%, 17% and 4% for the disposable diaper,
      urine bag, collection pad and clean catch, respectively. The average user ratings
      on a 0-10 (0 = inconvenient, 10 = convenient) scale were 9.0, 4.7, 7.3 and 2.5,
      respectively. Subsequently, the best rated method, the disposable polyacrylate
      diaper was tested with hydroxy-tebuconazole as an exposure biomarker for the
      fungicide tebuconazole and creatinine for urine density adjustment. After LC
      MS/MS analysis, the recoveries of hydroxy-tebuconazole in the range of 0.05-25
      ng/mL were on average 106%, and for creatinine 87%. Precisions (relative standard
      deviation) were for both 3%. The overall procedure including collection and
      extraction was assessed, resulting in three out of seven positive samples. Based
      on this study, the disposable diaper is a suitable method for urine collection of
      non-toilet-trained children for biomonitoring of tebuconazole. This method can
      serve as a basis for extension to other substances of interest.

PMID- 30292885
TI  - Characterization of acute intrastriatal effects of paraoxon on in vivo
      dopaminergic neurotransmission using microdialysis in freely moving rats.
AB  - Paraoxon (POX) is an extremely neurotoxic organophosphorous compound (OP) which
      main toxic mechanism is the irreversible inhibition of cholinesterase. Although
      the cholinergic system has always been linked as responsible for its acute
      effects, experimental studies have suggested that the dopaminergic system also
      may be a potential target for OPs. Based on this, in this study, the acute
      intrastriatal effects of POX on dopaminergic neurotransmission were characterized
      in vivo using brain microdialysis in freely moving rats. In situ administration
      of POX (5, 25 and 50 nmol, 60 min) significantly increased the striatal dopamine
      overflow (to 435 +/- 79%, 1066 +/- 120%, and 1861 +/- 332%, respectively),
      whereas a lower concentration (0.5 nmol) did not affect dopamine levels.
      Administration of POX (25 nmol) to atropine (15 nmol) pretreated animals,
      produced an increase in dopamine overflow that was ~63% smaller than those
      observed in animals not pretreated. Administration of POX (25 nmol) to
      mecamylamine (35 nmol) pretreated animals did not significantly affect the POX
      induced dopamine release. Our results suggest that acute administration of POX
      increases the dopamine release in a concentration-dependent way, being this
      release dependent on acetylcholinesterase inhibition and mediated predominantly
      by the activation of striatal muscarinic receptors, once the muscarinic
      antagonist atropine partially blocks the POX-induced dopamine release.

PMID- 30292886
TI  - Diagnosis of Cryptococcus gattii Infection Based on Endoscopic Ultrasound and
      Fine Needle Aspiration of a Lung Mass.

PMID- 30292884
TI  - Role of body composition and physical activity on permethrin urinary biomarker
      concentrations while wearing treated military uniforms.
AB  - Wearing of permethrin treated clothing is becoming more prevalent in military and
      outdoor occupational and recreational settings, as a personal protection measure
      against vector borne diseases transmitted through arthropods (e.g., malaria, Lyme
      disease). The goal of the study was to prospectively examine permethrin exposure
      among new U.S. Army recruits who had just been issued permethrin-treated uniforms
      over a 10-week military training period and whether individual body composition
      (percent body fat, %BF) and physical workload (total energy expenditure, TEE)
      influenced the exposure. Exposure was assessed by quantification in urine of
      three permethrin metabolites, 3-phenoxybenzoic acid (3-PBA), and cis- and trans-3
      (2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid. Although there
      was individual variability, urinary concentrations and estimated dose levels
      decreased over the 10-week period. Mixed models demonstrated that 10% higher %BF
      was significantly associated with 4.42% higher 3-PBA concentrations and a 10%
      higher daily TEE was significantly associated with a 10.57% higher 3-PBA
      concentrations. Additional factors influencing exposure included sex, number of
      uniform launderings, and wear- time (hours per previous day).

PMID- 30292887
TI  - Identifying Outcomes in Clinical Trials of Fistulizing Crohn's Disease for the
      Development of a Core Outcome Set.
AB  - Fistulizing complications develop in approximately one third of patients with
      Crohn's disease (CD), resulting in morbidity and impaired quality of life.1 Sites
      of fistulae most commonly include perianal fistulae, but also enterocutaneous,
      enteroenteric, enterovesical, and rectovaginal. Its management requires combined
      medical and surgical strategies to prevent abscess formation and induce healing.
      Biologic agents have improved the medical treatment of CD-related fistulae, but
      many patients still require surgical intervention. Hence, there is considerable
      interest in the development of novel pharmaceutical agents to treat fistulizing
      CD.

PMID- 30292888
TI  - The Gut-Brain Axis and the Microbiome: Mechanisms and Clinical Implications.
AB  - BACKGROUND & AIMS: Based largely on results from preclinical studies, the concept
      of a brain-gut microbiome axis has been established, mediating bidirectional
      communication between the gut, its microbiome, and the nervous system. Limited
      data obtained in human beings suggest that alterations in these interactions may
      play a role in several brain-gut disorders. METHODS: We reviewed the preclinical
      and clinical literature related to the topic of brain-gut microbiome
      interactions. RESULTS: Well-characterized bidirectional communication channels,
      involving neural, endocrine, and inflammatory mechanisms, exist between the gut
      and the brain. Communication through these channels may be modulated by
      variations in the permeability of the intestinal wall and the blood-brain
      barrier. Brain-gut microbiome interactions are programmed during the first 3
      years of life, including the prenatal period, but can be modulated by diet,
      medications, and stress throughout life. Based on correlational studies,
      alterations in these interactions have been implicated in the regulation of food
      intake, obesity, and in irritable bowel syndrome, even though causality remains
      to be established. CONCLUSIONS: Targets within the brain-gut microbiome axis have
      the potential to become targets for novel drug development for brain-gut
      disorders.

PMID- 30292889
TI  - Low Rates of Linkage and Retention Into Care Among Patients With Chronic HBV
      Infection.
AB  - Successful linkage and retention of newly diagnosed hepatitis B virus (HBV)
      patients is critical for disease monitoring. Existing studies have demonstrated
      significant gaps in the HBV care continuum among U.S. veterans1 and have mostly
      focused on adherence to laboratory testing or initial linkage. However, retention
      is especially important, given that decisions to start antiviral therapies are
      often not made until subsequent evaluation, and studies report high rates of
      becoming treatment-eligible among patients who were not eligible at initial
      evaluation.2 Given the existing system and socioeconomic barriers in access to
      care, understanding contributors to gaps and delays in HBV linkage and retention
      among safety-net populations is critical. We aim to evaluate prevalence and
      predictors of linkage and retention among HBV patients at an urban safety-net
      hospital.

PMID- 30292890
TI  - Unlocked potential of dynamic elements in protein structures: channels and loops.
AB  - Enzymes are nature's powerful catalytic proteins to perform reactions with often
      outstanding activity, selectivity and specificity. Moreover, the access to non
      natural functions of biocatalysts can be facilitated by enzyme engineering. While
      rational approaches are often focused on an enzyme's active site, from random
      directed evolution we know that further functional hotspots must exist beyond the
      active site. Addressing flexible structural elements of these biocatalysts like
      loops and channels in enzyme engineering has the potential to fill this knowledge
      gap. The structural dynamics of enzyme catalysts are vital to promote their
      remarkable functions. This influences for example the access, recognition and
      orientation of substrates. Herein, we review recent examples of loop and channel
      engineering and classify them according to their use of simulation methodologies,
      predictions prior to engineering, the engineering methodologies themselves and
      discoveries found after the engineering. Thereby we highlight current
      possibilities and make suggestions to further unlock the potential of this yet
      underexplored strategy.

PMID- 30292891
TI  - Does the use of adjunct urine LAM in HIV-infected hospitalized patients reduce
      the utilization of health care resources? A post hoc analysis of the LAM multi
      country randomized control trial.
AB  - BACKGROUND: The World Health Organisation (WHO) recommends the use of adjunctive
      urine lipopolysaccharide lipoarabinomannan (LAM) testing in hospitalized HIV
      infected persons with suspected tuberculosis (TB) and a CD4 count <100 cells/ml.
      However, the recommendation is conditional and uptake by individual treatment
      programs depends on perceived additional benefit. The aim of this study was to
      determine if adjunctive LAM testing had additional clinical benefits including
      reduction in health care-related use of resources. METHODS: We performed a post
      hoc analysis of a published multicenter multinational randomized control trial
      that showed an ~20% mortality benefit in HIV-infected hospitalized patients who
      underwent adjunctive LAM testing as part of their diagnostic workup. In that
      parent study adult HIV-infected hospitalized patients with suspected TB (n=2528)
      were randomly allocated to either routine diagnostics (smear-microscopy, Xpert
      MTB/RIF, and culture; n=1271), or routine diagnostics plus adjunctive urine LAM
      testing (n=1257). Data were further analyzed to determine if there were other
      potential benefits of LAM usage based on CD4 count and illness severity. Aspects
      evaluated included: (i) reduction in the number of diagnostic sputum samples
      tested, (ii) utilization of additional imaging, (III) disease resolution based on
      follow-up signs and symptoms of illness severity, and (IV) reduction in hospital
      readmission. RESULTS: Adjuvant LAM did not reduce the number of diagnostic sputum
      samples requested, the need for additional imaging, or the hospital readmission
      rate. However, adjunctive LAM was associated with a more rapid rate of disease
      resolution (dyspnea) in the severely ill subgroup. Higher LAM grade (grade 4-5),
      compared to lower grade positivity (<=3), was associated with lower use of
      ultrasound, lower Karnovsky performance score, lower CD4 cell count, and shorter
      time to culture positivity. CONCLUSIONS: Although, in the parent study adjunct
      LAM was associated with a mortality benefit, in the secondary analysis, no
      benefit could be demonstrated with respect to the number of diagnostic sputum
      samples requested, the use of additional imaging, or hospital readmission rates.
      However, given the limitations of the present study, further appropriately
      designed studies are required to determine the effect of adjunct urine LAM on
      utilization of health care resources. TRIAL REGISTRATION: This trial is
      registered with ClinicalTrials.gov, number NCT01770730.

PMID- 30292892
TI  - The impact of earlier intervention by an antimicrobial stewardship team for
      specific antimicrobials in a single weekly intervention.
AB  - OBJECTIVE: The objective of this study was to evaluate the effects of earlier
      intervention by an antimicrobial stewardship team (AST) on antimicrobial use,
      antimicrobial resistance rates, and the clinical outcomes, without changing the
      weekly intervention schedule. METHODS: A retrospective study was conducted at
      Fukuoka University Hospital between April 2013 and March 2016. The effects were
      compared among three study periods (SP): SP1 (patients receiving anti-methicillin
      resistant Staphylococcus aureus agents and carbapenems for >=14 days), SP2
      (patients receiving specific antimicrobials for >=14 days), and SP3 (patients
      receiving specific antimicrobials regardless of the duration of treatment).
      RESULTS: The timing of AST intervention was shortened from an average of 15.5days
      after administration in SP1 to 4.2 days in SP3. The antimicrobial use density
      (AUD) of carbapenems and piperacillin-tazobactam decreased significantly (SP2 vs.
      SP3, p<0.05), and the costs of specific antimicrobials decreased (SP1, US$
      1080000; SP2, US$ 944000; SP3, US$ 763000). The rates of carbapenem resistance
      among Pseudomonas aeruginosa isolates showed a significant reduction from 16.2%
      in SP2 to 8.7% in SP3 (p<0.05). The mortality rate and length of stay did not
      change during the study period. CONCLUSIONS: Earlier intervention by an AST could
      contribute to the proper use of antimicrobials without adversely affecting
      patient outcomes.

PMID- 30292893
TI  - Towards a better understanding of dry binder functionality.
AB  - It is of great importance to get a deeper understanding of the binding behaviour
      and functionality of different types of dry binders, since dry binders are
      crucial to ensure appropriate properties of dry granules and tablets. Based on
      previous studies, the most effective dry binders of chemically different types
      have been chosen to apply a new approach analysing the compressibility of tablets
      made from pure dry binders. Therefore, tablets were compressed at different
      tableting speeds to reveal binding behaviour of dry binders. Viscoelasticity,
      plasticity or abrasiveness were derived from force-displacement curves of
      tablets, which were manufactured at varying tableting pressure. In addition,
      elastic recovery, tabletability, fracture energy and out-of-die Heckel analysis
      were performed in order to get a comprehensive understanding on mechanical
      properties of dry binder for tableting. The new approach indicated explanations
      for results of previous studies in terms of tablet tensile strength, friability
      and dry granule properties. It enables a rational selection of dry binders for
      certain processes.

PMID- 30292894
TI  - Improved oral bioavailability of notoginsenoside R1 with sodium glycocholate
      mediated liposomes: Preparation by supercritical fluid technology and evaluation
      in vitro and in vivo.
AB  - The chief objective of this research was to appraise liposomes embodying a bile
      salt, sodium glycocholate (SGC), as oral nanoscale drug delivery system to
      strengthen the bioavailability of a water-soluble and weakly penetrable
      pharmaceutical, notoginsenoside R1 (NGR1). NGR1-loaded liposomes were prepared
      with the improved supercritical reverse evaporation (ISCRPE) method and the
      preparation conditions were optimized with response surface methodology (RSM).
      The mean encapsulation efficiency (EE), particle size, and polydispersity index
      (PDI) of the optimized liposomal formulation (NGR1@Liposomes) were 49.49%, 308.3
      nm, and 0.229, respectively. SGC-mediated liposomes (NGR1@SGC-Liposomes) were
      formulated based on the optimal preparation conditions and the mean EE, particle
      size, and PDI were 41.51%, 200.1 nm, and 0.130, respectively. The in vitro Caco-2
      cellular uptake of fluorescent marker was increased by loading into NGR1@SGC
      Liposomes as compared with the conventional liposomes. Furthermore, the
      intestinal permeability as well as the intestinal absorption of NGR1 were both
      significantly improved with NGR1@SGC-Liposomes as the nanovesicles. The in vivo
      pharmacokinetic study results showed that AUC0-t value of NGR1@SGC-Liposomes and
      NGR1@Liposomes was 2.68- and 2.03-fold higher than that of NGR1 aqueous solution,
      respectively. The AUC0-t of the NGR1@SGC-Liposomes group was significantly higher
      than that of NGR1@Liposomes. Thus, ISCRPE method is a feasible method for the
      preparation of water-soluble drug-loaded liposomes and bile salt-mediated
      liposomes may enhance the oral absorption of water-soluble and poorly permeable
      drugs.

PMID- 30292895
TI  - Inhibition of LDL oxidation and inflammasome assembly by nitroaliphatic
      derivatives. Potential use as anti-inflammatory and anti-atherogenic agents.
AB  - We have previously shown the antioxidant and anti-inflammatory properties of
      several para-substituted arylnitroalkenes. Since oxidative stress and
      inflammation are key processes that drive the initiation and progression of
      atherosclerosis, in the present work the antioxidant, anti-inflammatory and anti
      atherogenic properties of an extended library of aryl-nitroaliphatic derivatives,
      including several newly designed nitroalkanes, was explored. The antioxidant
      capacity of the nitroaliphatic compounds, measured using the oxygen radical
      absorbance capacity assay (ORAC) showed that the p-methylthiophenyl-derivatives
      were about three times more effective than Trolox to prevent fluorescein
      oxidation, independently of the presence or the absence of the double bond next
      to the nitro group. The peroxyl radical scavenger capacity of the p
      dimethylaminophenyl-derivatives was even higher, being the reduced form of these
      compounds even more active. In fact, while the antioxidant capacity of 1
      dimethylamino-4-(2-nitro-1Z-ethenyl)benzene and 1-dimethylamino-4-(2-nitro-1Z
      propenyl)benzene was 4.2 +/- 0.1 and 5.4 +/- 0.1 Trolox Eq/mol, respectively;
      ORAC values obtained with the ethyl and the propyl derivatives were 10 +/- 1 and
      13 +/- 2 Trolox Eq/mol, respectively. The p-dimethylamino-derivatives, especially
      the nitroalkanes, were also able to prevent LDL oxidation mediated by peroxyl
      radicals. Oxygen consumption due to the oxidation of fatty acids was delayed in
      the presence of the dimethylamino substituted compounds, only the alkanes
      interrupted the chain of lipid oxidations decreasing the rate of oxygen
      consumption. Although the formation of foam cells in the presence of oxidized-LDL
      (oxLDL) remained unaffected, the molecules containing the dimethylamino moiety
      were able to decrease the expression of IL-1beta in LPS/INF-gamma challenged
      macrophages.

PMID- 30292896
TI  - Activity-guided development of potent and selective toll-like receptor 9
      antagonists.
AB  - TLR9 is one of the major innate immune receptors expressed in the endosomes of
      pDCs and B cells in humans. Aberrant TLR9 activation is implicated in several
      autoimmune and metabolic disorders as well as in sepsis, making this receptor an
      important therapeutic target, though specific TLR9 antagonists are yet to be
      available for clinical use. Here we elucidate the importance of specific
      physiochemical properties through substitution patterns in quinazoline scaffold
      to achieve potent hTLR9 inhibition at < 50 nM as well as > 600 fold selectivity
      against hTLR7, another closely related TLR that shares downstream signaling with
      TLR9 but plays distinct roles in physiology and pathology. Assays were performed
      using hPBMC and reporter cell lines. Favorable in vitro ADME profile,
      pharmacokinetics as well as validation in a clinically relevant in vivo TLR9
      inhibition efficacy model in mice establish these novel TLR9-antagonists as
      candidate therapeutic agents in relevant clinical contexts.

PMID- 30292897
TI  - Synthesis and structure-activity relationship study of arylsulfonamides as novel
      potent H5N1 inhibitors.
AB  - H5N1 virus, one subtype of highly pathogenic influenza A virus in human
      infection, has recently received attention due to its unpredictable and high
      mortality. In this study, a series of arylsulfonamide derivatives were identified
      as improved H5N1 inhibitors for the influenza treatment by systematic structure
      activity relationship investigation. Among them, the most potent H5N1 inhibitor
      3h exhibited excellent antiviral activity against H5N1 virus with EC50 value of
      0.006 MUM and selectivity index 33543.3. Moreover, the molecular docking of 3h
      with M2 proton channel protein provides practical way for understanding the
      inhibition of H5N1 with this kind of compounds.

PMID- 30292899
TI  - Three years of colorectal cancer screening in Denmark.
AB  - BACKGROUND: The Danish National Colorectal Cancer Screening Programme was
      implemented in March 2014 and is offered free of charge to all residents aged 50
      74 years. The aim of this study is to compare performance indicators from the
      Danish National Colorectal Cancer Screening Programme to the recommendations from
      European Guidelines in order to assure the quality of the programme and to
      provide findings relevant to other population-based colorectal cancer screening
      programmes. METHODS: Based on data from the Danish Colorectal Cancer Screening
      Database, we evaluated all performance indicators for which the European
      Guidelines provided acceptable level, desirable level or the level from first
      screening rounds in population-based studies using FIT. RESULTS: All performance
      indicators were above the acceptable level and/or in line with the level from the
      first screening round in population-based studies using FIT. Whenever the
      European Guidelines provided a desirable level for a performance indicator, the
      Danish National Colorectal Cancer Screening Programme was close to or above this
      desirable level. CONCLUSIONS: Compared to the European Guidelines, all
      performance indicators were above the acceptable level and close to the desirable
      level. Based on these findings, the implementation of the National Danish
      Colorectal Cancer Screening Programme is considered a success and the programme
      is hopefully in the process of reducing colorectal cancer morbidity and mortality
      in Denmark. This study provides relevant information for comparisons to other
      population-based public service colorectal cancer screening programmes as well as
      for future revisions of guidelines.

PMID- 30292898
TI  - In search of constrained FTY720 and phytosphingosine analogs as dual acting
      anticancer agents targeting metabolic and epigenetic pathways.
AB  - A series of compounds containing pyrrolidine and pyrrolizidine cores with
      appended hydrophobic substituents were prepared as constrained analogs of FTY720
      and phytosphingosine. The effect of these compounds on the viability of cancer
      cells, on downregulation of the nutrient transport systems, and on their ability
      to cause vacuolation was studied. An attempt to inhibit HDACs with some phosphate
      esters of our analogs was thwarted by our failure to reproduce the reported
      inhibitory action of FTY720-phosphate.

PMID- 30292900
TI  - A systematic review of shunt-related extraneural metastases of primary central
      nervous system tumors.
AB  - Extraneural metastasis (ENM) of primary central nervous system (CNS) tumors is an
      uncommon occurrence. Case reports and case series describe ENM after shunting,
      but this phenomenon has not been well characterized. In this review we aim to
      better understand the risk factors and clinical implications of ENM associated
      with shunting. A literature search of cases of ENM related to shunt placement in
      patients with primary CNS tumors reported through January 2018 was performed
      using PubMed and Google Scholar. We identified 106 cases of ENM of primary CNS
      tumors related to shunt placement. The three most common tumor histologies
      resulting in ENM were germinoma (24%), medulloblastoma (21%), and glioblastoma
      (11%). Of the patients with ENM, 48% had leptomeningeal spread and 37% had brain
      or spinal cord metastasis. Mean survival time from shunt placement was 13 months.
      Ventriculoatrial-shunted cases had higher rates of widespread metastasis and
      shorter average survival time from shunt placement (2 months) than the average of
      all types of shunts. Given the known association with ENM, careful consideration
      should be given to shunt placement in patients with primary CNS tumors,
      especially germinomas, medulloblastomas, and glioblastomas. Appropriate
      surveillance should be instituted after shunt placement, and leptomeningeal or
      neural metastasis should prompt the consideration of potential ENM. When
      considering distal shunt options, our review suggests that ventriculoatrial
      shunts should be avoided if possible. For truly obstructive pathologies, the risk
      of ENM is a further indication to consider other treatment options such as
      endoscopic third ventriculostomy rather than shunt placement.

PMID- 30292901
TI  - Physical intensity of stimuli modulates motor inhibition by affecting response
      selection processes in right inferior frontal regions.
AB  - Response inhibition is a central aspect of cognitive control. Yet, only recently
      the role of sensory mechanisms for response inhibition has been addressed and
      neurophysiological mechanisms are far from being understood. Here we ask in how
      far the physical intensity of stimuli is a relevant perceptual factor modulating
      motor inhibitory control. We investigated how different physical (objective)
      stimulus and the subjectively perceived stimulus magnitude modulated response
      inhibition and its neurophysiological correlates. To this end we used a
      somatosensory GO/NOGO task in combination with EEG recordings and applied
      temporal signal decomposition and source localization methods. The behavioral
      (false alarm) data clearly demonstrated that response inhibition performance was
      worse in the subjective and objective stimulation condition as compared to the
      reference stimulation condition with higher stimulus magnitude. Despite primary
      perceptual aspects were manipulated, neurophysiological correlates of lower-level
      perceptual and attentional selection processes did not explain effects on overt
      response inhibition behavior. Rather, neurophysiological processes at the
      response selection level were modulated. These were associated with activation
      differences in the right inferior frontal gyrus and suggest that "braking
      processes" enabling the inhibition of a to-be-executed motor response were
      modulated. The modulation of these braking processes depends on objective
      physical magnitude of incoming sensory information and not the subjectively
      perceived stimulus magnitude.

PMID- 30292902
TI  - Effects of cognitive judgement bias and acute antidepressant treatment on
      sensitivity to feedback and cognitive flexibility in the rat version of the
      probabilistic reversal-learning test.
AB  - Depressive disorders are often associated with cognitive biases. In this study,
      we investigated, in an animal model, whether cognitive judgement bias, measured
      as a stable and enduring behavioural trait, could modulate the effects of
      antidepressant drugs on other cognitive processes associated with depression. For
      this purpose, we identified rats displaying 'pessimistic' and 'optimistic' traits
      in a series of ambiguous-cue interpretation (ACI) tests. Subsequently, in the
      preclinical version of the probabilistic reversal-learning (PRL) test, allowing
      multiple reversals within a test session, we compared the effects of acute
      administration of 5 different antidepressant (AD) drugs (agomelatine,
      escitalopram, clomipramine, mirtazapine and venlafaxine) on cognitive flexibility
      and sensitivity to positive/negative feedback in optimistic and pessimistic
      animals. We report that, following acute treatment with agomelatine, the
      proportion of lose-shift behaviours in the PRL test was significantly reduced in
      pessimistic animals compared to optimists. We also demonstrate that acute
      treatment with another antidepressant drug, mirtazapine, significantly increased
      the sensitivity of rats to positive feedback, as indexed by the increased
      proportion of win-stay behaviour following probabilistic reward. This effect was
      independent of cognitive bias and was associated with a reduced number of
      reversals made by the animals. Three other tested drugs had no significant
      effects on behavioural measures assessed in our study.

PMID- 30292903
TI  - rTMS pre-treatment effectively protects against cognitive and synaptic plasticity
      impairments induced by simulated microgravity in mice.
AB  - During space flight, microgravity has several negative effects on cognitive
      functions and learning and memory abilities. However, there are few effectively
      preventive methods that have been developed yet. Previous studies showed that
      repetitive transcranial magnetic stimulation (rTMS), as a novel non-invasive
      technique, alleviated cognitive dysfunctions and facilitated synaptic plasticity.
      In the present study, we used a hindlimb unloading (Hu) mouse model to simulate
      microgravity conditions. And then, we investigated whether rTMS played a
      neuroprotective role in a Hu mouse model. Behavioral experiments including Open
      field test and Novel object recognition test were performed. These results showed
      that spontaneous activity and recognition memory were reduced by Hu, while rTMS
      significantly protected against the harmful effect. Furthermore,
      electrophysiological recordings were performed to examine the level of synaptic
      plasticity including paired-pulse facilitation (PPF) and long-term potentiation
      (LTP). In the hippocampus DG and CA1 regions, dendritic spine density was
      measured using Golgi-Cox staining. Our data showed that rTMS effectively impeded
      the impairment of PPF and LTP, as well as the decrease of spine density induced
      by Hu. Subsequently, Western blot assay showed that rTMS inhibited the
      downregulation of CREB/BDNF signaling network associated proteins in Hu mice. It
      suggests that rTMS pre-treatment plays a neuroprotective role in protecting
      against cognitive impairments and synaptic plasticity deficits induced by
      microgravity stimulation.

PMID- 30292904
TI  - Atlantoaxial rotatory dislocation in a patient with psoriatic spondyloarthritis.

PMID- 30292905
TI  - Use Side Branch of the Aortic Graft to Facilitate Coronary Reconstruction During
      Complex Aortic Surgery.
AB  - The interposition graft could be used for difficult coronary reconstruction
      during aortic root replacement. We introduced a new technique that utilizes side
      branch of an aortic graft to facilitate coronary reconstruction. The present
      study describes this technique and its outcomes. We retrospectively reviewed 234
      patient charts of those who underwent aortic root replacement between January
      2013 and November 2017. Within this group, 6 patients required coronary
      reconstruction with branches of aortic graft and were included in this study. All
      patients were reoperative cases, 3 of which were for acute type A aortic
      dissection. The mean cardiopulmonary and aortic cross clamp times were 317.2 +/-
      35.1 minutes and 153.3 +/- 75.4 minutes, respectively. All patients survived to
      discharge with a median hospital stay of 20.5 days (interquartile range: 13.75
      27.75). During a median follow-up of 221 days (interquartile range: 197.78-1208),
      no patients experienced major adverse cardiovascular events. Four patients
      underwent radiographic follow-up, which confirmed patent interposition grafts
      (5/5). The use of branches from the aortic graft for coronary reconstruction is
      feasible with satisfactory outcomes.

PMID- 30292906
TI  - Raman investigation of the pigment families in recent and fossil brachiopod
      shells.
AB  - Shells of the three subphyla of extant and extinct representatives of the phylum
      Brachiopoda display coloured patterns with diverse shapes and at different
      degrees. These colourations are readily visible in natural light but are best
      revealed under UV light for the fossils concerned. To identify these pigments,
      Raman spectroscopy has been used for the first time on brachiopod shells. The
      widespread identified pigments belong to the carotenoid family, best represented
      in all the animal kingdom, the second one concerns the melanin/melanin-like
      pigments and, surprisingly, additional molecules of the cytochrome family are
      revealed for the first time in one of the brachiopod shells studied. The putative
      functions of shell pigmentation, still under debate, are discussed.

PMID- 30292907
TI  - Fourier transform infrared spectroscopy based spectral biomarkers of metastasized
      breast cancer progression.
AB  - Breast cancer is a global health issue and the second leading cause of cancer
      death in women. Breast cancer tends to migrate to bone and causes bone metastases
      which is ultimately the cause of death. Here, we report the use of FTIR to
      identify spectral biomarkers of cancer progression on 3D in vitro model of breast
      cancer bone metastasis. Our results indicate that the following spectral
      biomarkers can monitor cancer progression, for example, lipids (CH2
      asymmetric/CH2 symmetric stretch), Amide I/Amide II, and RNA/DNA. Principal
      component analysis also confirmed the involvement of protein, lipids and nucleic
      acids in cancer progression on sequential culture. The collective observations
      from this study suggest successful application of FTIR as a non-invasive and
      accurate method to identify biochemical changes in cancer cells during the
      progression of breast cancer bone metastasis.

PMID- 30292908
TI  - An evidence of chemically and physically mediated migration of 238U and its
      daughter isotopes in the vicinity of a former uranium mine.
AB  - The present study reports the evidence of a radioactive contamination in a
      wetland located downstream from a former French U mine in Brittany. This
      situation is demonstrated according to the measurements of gamma dose rates and
      activity ratios of 238U and 232Th-decay series nuclides, which give the
      justification regarding the accumulation of significant amounts of 238U, 230Th
      and 226Ra in this wetland. The dose rate map highlights an increase of radiation
      level along the former mine water pathway compared to the background value, with
      a maximum value of 1500 nSv.h-1 reached in the wetland. Activities of 238U, 230Th
      and 226Ra and 232Th/238U ratios measured in surface wetland soils are
      significantly higher than the geochemical background. 230Th/238U ratios less than
      unity suggest a preferential accumulation of U in the wetland, compared to its
      daughter isotopes. Moreover, the loss of 226Ra compared to 230Th raises its
      higher mobility compared to its parent isotope. In far-field sediments,
      226Ra/238U ratio of 1.76 implies a different geochemical behavior of U, which
      could be explained by the occurrence of mobile U species. The results suggest
      that contamination of wetland soils and far-field sediments could result from
      discharges of underground mine waters.

PMID- 30292909
TI  - Meteorological and soil surface effects in gamma radiation time series -
      Implications for assessment of earthquake precursors.
AB  - Monitoring of environmental radioactivity for the purpose of earthquake
      prediction requires the discrimination of anomalies of non-tectonic origin from
      seismically-induced anomalies. This is a challenging task as time series of
      environmental radioactivity display a complex temporal pattern reflecting a wide
      range of different physical processes, including meteorological and surface
      effects. The present study is based on the detailed time series of gamma
      radiation from the Eastern North Atlantic (ENA) site in the Azores, and on very
      high resolution precipitation intensity and soil moisture time series. The
      results show that an abrupt shift in the average level of the gamma radiation
      time series previously reported as a potential earthquake precursor can also be
      explained by a corresponding abrupt change in soil moisture. It was concluded
      that the reduction of false positive earthquake precursors requires the detailed
      assessment of both precipitation and soil moisture conditions at high temporal
      resolution.

PMID- 30292910
TI  - SD-CNN: A shallow-deep CNN for improved breast cancer diagnosis.
AB  - Breast cancer is the second leading cause of cancer death among women worldwide.
      Nevertheless, it is also one of the most treatable malignances if detected early.
      Screening for breast cancer with full field digital mammography (FFDM) has been
      widely used. However, it demonstrates limited performance for women with dense
      breasts. An emerging technology in the field is contrast-enhanced digital
      mammography (CEDM), which includes a low energy (LE) image similar to FFDM, and a
      recombined image leveraging tumor neoangiogenesis similar to breast magnetic
      resonance imaging (MRI). CEDM has shown better diagnostic accuracy than FFDM.
      While promising, CEDM is not yet widely available across medical centers. In this
      research, we propose a Shallow-Deep Convolutional Neural Network (SD-CNN) where a
      shallow CNN is developed to derive "virtual" recombined images from LE images,
      and a deep CNN is employed to extract novel features from LE, recombined or
      "virtual" recombined images for ensemble models to classify the cases as benign
      vs. cancer. To evaluate the validity of our approach, we first develop a deep-CNN
      using 49 CEDM cases collected from Mayo Clinic to prove the contributions from
      recombined images for improved breast cancer diagnosis (0.85 in accuracy, 0.84 in
      AUC using LE imaging vs. 0.89 in accuracy, 0.91 in AUC using both LE and
      recombined imaging). We then develop a shallow-CNN using the same 49 CEDM cases
      to learn the nonlinear mapping from LE to recombined images. Next, we use 89 FFDM
      cases from INbreast, a public database to generate "virtual" recombined images.
      Using FFDM alone provides 0.84 in accuracy (AUC = 0.87), whereas SD-CNN improves
      the diagnostic accuracy to 0.90 (AUC = 0.92).

PMID- 30292911
TI  - Production of various organic acids from different renewable sources by
      immobilized cells in the regimes of separate hydrolysis and fermentation (SHF)
      and simultaneous saccharification and fermentation (SFF).
AB  - The study was aimed at production of different organic acids (OA) (lactic,
      fumaric, or succinic) by various microbial cells (filamentous fungi Rhizopus
      oryzae (F-814, F-1127) and bacteria Actinobacillus succinogenes B-10111)
      immobilized into poly(vinyl alcohol) (PVA) cryogel from diverse renewable raw
      materials (wheat and rice straw, aspen and pine sawdust, Jerusalem artichoke
      stems and tubers, biomass of macro- and microalgae) under batch conditions. The
      process productivity, bulk output and OA concentrations were higher in case of
      using immobilized cells than in case of free cells under identical conditions. A
      higher OA productivity was reached via simultaneous enzymatic saccharification
      and microbial fermentation (SSF) of same raw materials as compared to their
      separate enzymatic hydrolysis and fermentation of accumulated reducing sugars
      (SHF). Maximal concentrations of all OAs studied were obtained for bioconversion
      of Jerusalem artichoke tubers. The immobilized cells were used in long-term
      conversion of various renewable materials to OAs in SSF.

PMID- 30292912
TI  - Biochar influences the succession of microbial communities and the metabolic
      functions during rice straw composting with pig manure.
AB  - The present study determined the dynamic changes of bacterial community
      structures and its metabolism functions in rice straw composting process with
      different types of biochar addition. Results showed that both wheat and maize
      straw biochar addition greatly increased the temperatures and germination index.
      Biochar addition influenced microbial community structure and metabolic
      characteristics of the compost. Firmicutes, Actinobacteria and Proteobacteria
      were the dominant phyla throughout the process, and both biochar addition
      significantly increased the relative abundance of Actinobacteria phylum,
      especially genus Saccharomonospora. The abundance of bacterial genes related to
      amino acid metabolism, carbohydrate metabolism and energy metabolism were also
      increased with biochar addition. Moreover, total nitrogen was strongly affected
      by biochar addition and had the greatest influence on the bacterial community
      structure. These results indicated that biochar addition improved the maturity
      and fertility of the compost product as well as significantly regulated the
      microbial community structure and functions during composting process.

PMID- 30292913
TI  - Validation of the stabilometer balance test: Bridging the gap between clinical
      and research based balance control assessments for stroke patients.
AB  - BACKGROUND: A pronounced discrepancy exists between balance assessments for
      stroke survivors that are used for clinical purposes and those used for research.
      Clinical assessments like the Berg Balance Scale generally have stronger
      ecological validity, whereas research-based assessments like posturography are
      generally more reliable and precise. We developed a stabilometer balance test
      (SBT) that aims to couple measurement reliability and precision to clinical
      meaningfulness by means of a personalized and adaptive test procedure. RESEARCH
      QUESTION: To examine the validity, reliability, and measurement error of the
      stabilometer balance test in inpatient stroke patients. METHODS: In this cross
      sectional study, inpatient stroke patients (FAC > 2) were tested on a
      stabilometer with adjustable resistance to mediolateral movement. A modified
      staircase procedure was used to adapt task difficulty (i.e., rotational
      stiffness) on a trial-by-trial basis. The main outcome was the threshold
      stiffness at which a patient could just stay balanced. Threshold stiffness was
      correlated with the Berg Balance Scale and posturography measurements to
      determine concurrent validity (N = 86). Test-retest reliability (N = 23) was
      analyzed with the Intraclass Correlation Coefficient (ICC). Floor and ceiling
      effects were assessed. The minimal detectable change was determined at individual
      and group level. RESULTS: Threshold rotational stiffness moderately correlated
      with the Berg Balance Scale (r=-0.559, p < 0.001), and the absolute path length
      of the center of pressure during posturography (r=0.348, p = 0.006). Test-retest
      reliability was good to excellent (ICC=0.869; 95%CI=0.696-0.944). There were no
      floor or ceiling effects. The minimal detectable change was sufficiently small to
      detect relevant changes in balance control both on individual and group level.
      RELEVANCE: The SBT is both a valid and reliable balance assessment in stroke
      patients. It is at least as precise as current clinically preferred measures and
      does not suffer from ceiling effects. Therefore, it is suitable for use in
      clinical practice as well as research.

PMID- 30292914
TI  - Mechanical work, kinematics, and kinetics during sit-to-stand in children with
      and without spastic diplegic cerebral palsy.
AB  - BACKGROUND: Sit-to-stand (STS) is one of the most common fundamental activity in
      daily life. The pathology of the neuromuscular control system in children with
      spastic diplegic cerebral palsy (SDCP) could contribute to atypical movement
      patterns leading to the inefficiency performance including the STS task. However,
      there was also a lack of evidence about kinematics, kinetics, and especially
      mechanical work during the STS task in children with SDCP aged 7-12 years old.
      RESEARCH QUESTION: What were the differences in mechanical work, kinematics and
      kinetics during STS task between children with SDCP and typically developing (TD)
      children? METHODS: Eleven children with SDCP (GMFCS I-II) and eleven age and
      gender-matched control TD children with an age range of 7-12 years were enrolled.
      Motion analysis and force plate systems were used to collect data. All
      participants performed the STS task from an adjustable chair. Independent sample
      t-test and two-way analysis of variance were used in this study. RESULTS: The
      children with SDCP took a longer time and used more mechanical work during STS
      than TD children. At the beginning of the STS task, children with SDCP showed
      more trunk flexion and posterior pelvic tilting; in addition, during the STS task
      they also presented more trunk, hip, and knee flexion than TD children. However,
      the children with SDCP showed less ankle dorsiflexion compared with TD children.
      For the kinetic variables, asymmetry was found in children with SDCP. The maximum
      hip and knee extension moment, plantar flexion moment, and peak vertical ground
      reaction force (GRF) of the non-dominant leg were higher than the values of the
      dominant leg in these children. SIGNIFICANCE: Even though, children with SDCP who
      are able to independently STS. They were also a mechanically less efficient
      performance during STS task. Therefore, this task still needs to be trained
      during rehabilitation sessions.

PMID- 30292915
TI  - Implications of human induced pluripotent stem cells in metabolic disorders: from
      drug discovery toward precision medicine.
AB  - Human induced pluripotent stem cells (hiPSCs) enable in vitro high-throughput
      pharmacological screening assays of diseased tissue. Together with recent genome
      wide association studies (GWAS), hiPSCs enable the identification of key
      mutations for the development of effective treatments based on precise drugs. In
      concert with CRISPR/Cas9 systems, hiPSC technology can reveal therapeutic targets
      in metabolic disorders. The ex vivo CRISPR correction of autologous patient
      derived hiPSCs has led to the development of replacement cell therapies,
      providing better patient prognoses.

PMID- 30292916
TI  - Design strategies for chemical-stimuli-responsive programmable nanotherapeutics.
AB  - Chemical-stimuli-responsive nanotherapeutics have gained great interest in drug
      delivery and diagnosis applications. These nanotherapeutics are designed to
      respond to specific internal stimuli including pH, ionic strength, redox,
      reactive oxygen species, glucose, enzymes, ATP and hypoxia for site-specific and
      responsive or triggered release of payloads and/or biomarker detections. This
      review systematically and comprehensively addresses up-to-date technological and
      design strategies, and challenges nanomaterials to be used for triggered release
      and sensing in response to chemical stimuli.

PMID- 30292917
TI  - Application of nanotechnology to improve the therapeutic benefits of statins.
AB  - Hyperlipidemia is defined as an elevated level of lipids and lipoproteins in the
      blood and is considered to be a significant risk factor for accelerating the
      process of atherosclerosis and, consequently, cardiovascular disease. The level
      of cholesterol, especially low-density lipoprotein cholesterol (LDL-C), is
      commonly elevated in hyperlipidemia and represents the primary therapeutic
      target. Statins are a group of drugs that function by inhibiting 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase and are extremely efficacious in
      reducing elevated LDL-C in the serum and preventing atherosclerotic
      cardiovascular disease. However, statins have some limitations, such as poor
      aqueous solubility, low oral absorption, and, consequently, limited
      bioavailability when administered by the oral route. The field of nanotechnology
      is now well developed and some of these newer nanotechnology strategies offer
      systems with enhanced aqueous solubility of the statin, increased absorption,
      bioavailability, and controlled release of the statin at the site of
      administration. Here, we discuss nano-sized drug delivery systems to enhance the
      therapeutic potential of statins.

PMID- 30292918
TI  - Evidence of prefrontal hyperactivation to food-cue reversal learning in
      adolescents with anorexia nervosa.
AB  - Food avoidance in anorexia nervosa (AN) has been hypothesized to occur as a
      result of deficits in reversal learning and altered neuronal processing of food
      cue relationships. Extant findings suggest that those with AN may rely on
      heightened recruitment of prefrontal regions during initial formation of food-cue
      learning and difficulty extinguishing these relationships may result from
      elevated insula activity. We tested this hypothesis by comparing behavioral and
      neuronal responses to food-cue acquisition and reversal between adolescents with
      AN and healthy controls. Compared to controls, acquisition of a food-cue
      association and its reversal were associated with elevated prefrontal activation
      in adolescents with AN. There were no significant differences between groups in
      insula activation and no behavioral differences in the ability to acquire or
      reverse the food-cue association. The results suggest that adolescents with AN
      recruit prefrontal regulatory networks to acquire and alter expectancies to food.
      This pattern of top-down prefrontal control suggests that clinical interventions
      that target changes in food-cue relationships and rely on cognitive control may
      be less effective. Interventions that alter behavior without reliance on this top
      down control may have advantages with this population.

PMID- 30292919
TI  - Role of Skin Tests in the Diagnosis of Immediate Hypersensitivity Reactions to
      Taxanes: Results of a Multicenter Study.
AB  - BACKGROUND: Immediate hypersensitivity reactions (HSRs) to taxanes have been
      increasing in recent years, but the importance of skin tests in allergological
      workup has not been established. OBJECTIVE: In our study we tried to evaluate the
      role of prick and intradermal tests in the diagnosis of HSRs to paclitaxel and
      docetaxel. METHODS: In this multicenter prospective study, we enrolled patients
      with immediate HSRs to the aforesaid agents. Skin tests were performed on these
      subjects and if results were negative, intradermal tests with the culprit drug
      were conducted. Patients with grade 1 reactions subsequently underwent graded
      challenge; in cases of grade 2 or 3 reactions and/or positive test results, the
      culprit drug was administered with a desensitization schedule. Skin tests were
      also performed in 30 control subjects exposed to the taxanes without HSRs.
      RESULTS: A total of 84 patients (63 with HSRs to paclitaxel and 21 to docetaxel)
      were recruited in the period July 2015 to July 2017 by 8 centers; 58 patients
      (69%) developed grade 2 or 3 reactions. Prick test results were negative in all
      the cases, whereas intradermal test results were positive in 14 patients (10 with
      paclitaxel [15.9%] and 4 with docetaxel [19%]). The positivity of skin tests
      significantly correlated with grade 3 reactions and cutaneous involvement during
      HSRs. Graded challenge was performed in 16 patients without problems and 58
      subjects underwent desensitization, which was well tolerated in all but 2 cases.
      In the control group, skin test results were negative in all the patients.
      CONCLUSIONS: Skin tests for taxanes seem useful and can be performed in the
      allergological workup of subjects with HSRs to these agents, especially in cases
      of severe reactions with cutaneous involvement.

PMID- 30292920
TI  - Desensitization to cross-reacting allergen in egg yolk and chicken meat.

PMID- 30292921
TI  - Risk of Postpartum Depression Among Women with Asthma.
AB  - BACKGROUND: Several epidemiological studies have suggested that the risk of
      depression is increased in patients with asthma, but the impact of asthma during
      pregnancy on postpartum depression remains unknown. OBJECTIVE: To assess the
      association between maternal asthma and postpartum depression in a population
      based cohort study retrieved from administrative databases. METHODS: A cohort of
      35,520 pregnancies in women with asthma during pregnancy and 197,057 pregnancies
      in women without asthma who delivered between 1998 and 2009 was extracted from
      the Quebec Asthma and Pregnancy Database. They were followed from the day of
      delivery up to 1 year postpartum. A generalized estimating equation model was
      used to estimate the adjusted odds ratios of postpartum depression with 95% CIs
      in women with asthma during pregnancy versus women without asthma. RESULTS:
      Postpartum depression within 1 year after delivery occurred in 6.1% of women with
      asthma versus 2.9% of women without asthma. After adjusting for several potential
      confounders, including depression/postpartum depression up to 10 years before
      pregnancy, we found that women with asthma were 58% more likely to experience
      postpartum depression within 1 year after delivery than women without asthma
      during pregnancy (adjusted odds ratio, 1.58; 95% CI, 1.50-1.67). CONCLUSIONS: Our
      findings suggest that women with asthma are more likely to suffer from postpartum
      depression. A close monitoring of signs of depression for pregnant women with
      asthma is indicated, allowing prompt and efficient interventions if needed.

PMID- 30292922
TI  - Drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: Proportion
      and determinants of underreporting to pharmacovigilance.

PMID- 30292923
TI  - Extended analysis of parent and child confidence in recognizing anaphylaxis and
      using the epinephrine autoinjector during oral food challenges.

PMID- 30292924
TI  - Does Changing Inhaler Device Impact Real-Life Asthma Outcomes? Clinical and
      Economic Evaluation.
AB  - BACKGROUND: Inhaler usability and deposition differ between devices. Change of
      device may therefore have an impact on clinical and economic outcomes. OBJECTIVE:
      To characterize clinical and economic asthma outcomes surrounding the change from
      a dry powder inhaler (DPI) to a pressurized metered-dose inhaler (pMDI) for fixed
      dose combination inhaled corticosteroid/long-acting beta agonist (FDC ICS/LABA)
      treatment. METHODS: Three retrospective cohort substudies using 2010 to 2015 data
      from the Korean Health Insurance and Review Assessment Service database were
      performed. Patients with asthma who received an FDC ICS/LABA pMDI for the first
      time after initially being on FDC ICS/LABA DPI were included. The following
      outcomes were assessed: (1) persistence of change to pMDI over 6 months, (2)
      clinical outcomes during the year after the change compared with the baseline
      year; and (3) noninferiority comparison of costs and effectiveness between
      patients changing to a pMDI and matched patients who continued their DPI.
      RESULTS: Patients who change inhalers seem to represent a more severe
      subpopulation. Fifty-eight percent of patients (95% CI, 56-60) persisted with the
      change. After the change in therapy, an increased proportion of patients (58.3%)
      remained free from severe exacerbations compared with the year before (47.4%; P <
      .001). Patients who changed to pMDIs had significantly less severe exacerbations,
      acute respiratory events, and lower short-acting beta agonist inhaler average
      daily dose, but higher average ICS daily dose (all P < .05), compared with
      matched patients remaining on a DPI. Total costs were similar between patients
      who changed to pMDI therapy compared with those remaining on a DPI. CONCLUSION:
      Changing from a DPI to a pMDI for FDC ICS/LABA asthma treatment can be as
      effective and cost-effective as remaining on a DPI.

PMID- 30292925
TI  - Visuomotor learning and unlearning in children and adolescents with tourette
      syndrome.
AB  - Tourette syndrome (TS) is a childhood-onset neurological condition characterised
      by an evolving repertoire of chronic motor tics and one or more phonic tics.
      Tics, like habits, are inflexible and repetitive behaviours that are acquired
      over a period of time. It has been proposed that tics arise in TS as a result of
      increased habit learning: which may bias the child to acquire automatic
      behaviours (i.e., tics) more readily than is normal and make it harder to unlearn
      maladaptive habits once they have been acquired. Using a well-established
      visuomotor adaptation task, we investigated motor learning in a group of children
      and adolescents with a clinical diagnosis of TS relative to a group of age and
      gender matched typically developing individuals. In particular, we quantified
      differences in the strength and quality of motor learning and unlearning in TS,
      and the consolidation of motor learning over a 24 h washout period. We
      demonstrated that there was a marginally significant decrease in learning rate in
      the individuals with TS relative to age and gender matched typically developing
      controls. However, this effect was not associated with tic severity and could be
      entirely accounted for by the severity of co-occurring ADHD symptoms. Thus, once
      ADHD symptoms had been accounted for, there were no between group differences in
      learning rate or the degree of learning observed. By contrast, and more
      importantly, we found that following learning the rate of forgetting (unlearning)
      was significantly negatively associated with motor tic severity, such that
      individuals with more severe tics took longer to unlearn previously learnt motor
      patterns of behaviour. This finding is consistent with the proposal that TS is
      associated with alterations in the striatal habit learning system and with the
      view that TS may make it harder to unlearn maladaptive motor habits once they
      have been acquired.

PMID- 30292926
TI  - Synthesis of the tetrasaccharide related to the repeating unit of the O-antigen
      from Azospirillum brasilense Jm125A2 in the form of its 2-aminoethyl glycoside.
AB  - Total chemical synthesis of the linear tetrasaccharide repeating unit beta-D-Glc
      (1 -> 2)-alpha-L-Rha-(1 -> 3)-alpha-L-Rha-(1 -> 2)-alpha-L-Rha-CH2CH2NH2 of the O
      antigen from Azospirillum brasilense Jm125A2 is accomplished through rational
      protecting group manipulations of commercially available monosaccharides and
      stereoselective glycosylations. The target tetrasaccharide in the form of its 2
      aminoethyl glycoside is obtained in ~24% yield over 10 steps following a linear
      strategy. The structure is particularly suitable for further glycoconjugate
      formation through the terminal free amine without hampering the reducing end
      stereochemistry.

PMID- 30292927
TI  - Synthesis and Photophysical Studies on N1-(2'-O,4'-C-Methyleneribofurano
      nucleoside-3'-yl)-C4-(coumarin-7-oxymethyl)-1,2,3-triazoles.
AB  - A series of eight N1-(2'-O,4'-C-methylene-beta-D-ribofuranonucleoside-3'-yl)-C4
      (coumarin-7-oxymethyl)-1,2,3-triazoles have been synthesized by Cu(I)-catalyzed
      azide-alkyne cycloaddition reaction of 3'-azido-3'-deoxy-2'-O,4'-C
      methyleneuridine and 3'-azido-3'-deoxy-2'-O,4'-C-methylene-5-methyluridine with 7
      propargyloxy coumarins in 82-88% yields. The synthesized coumarintriazolyl
      bicyclonucleoside conjugates possess an extra bridge between 2'-O and 4'-C in the
      nucleoside moiety, which facilitates its pre-organization into N-type sugar
      puckering. This was confirmed by X-ray crystal structure studies on one of the
      conjugates, i.e. on N1-(3'-deoxy-2'-O,4'-C-methylene-5-methyluridin-3'-yl)-C4-(4
      phenylcoumarin-7-oxymethyl)-1,2,3-triazole. Photophysical studies carried out on
      the synthesized compounds demonstrate that they possess useful level of
      fluorescence with Stokes shift of approximately 70 nm.

PMID- 30292928
TI  - Control of autoreactive B cells by IgM and IgD B cell receptors: maintaining a
      fine balance.
AB  - A substantial fraction of mature naive B cells recognize endogenous antigens, and
      this autoreactivity must be controlled to prevent autoantibody secretion.
      Selective downregulation of the IgM BCR on autoreactive B cells has long been
      appreciated, and recent findings illustrate how this might impose tolerance. The
      BCR isotype maintained on autoreactive B cells, IgD, is less sensitive to
      endogenous antigens than IgM. This reduced sensitivity may be conferred by
      structural properties of IgD and/or differential association with activating and
      inhibitory co-receptors. Once activated, autoreactive B cells are normally
      excluded from rapid plasma cell responses, but they can enter the germinal center
      and lose their autoreactivity through a mutation-selection process termed clonal
      redemption.

PMID- 30292929
TI  - Molecular and histological study on the effects of electrolytic electroporation
      on the liver.
AB  - This study examined the temporal physiological and molecular events following the
      treatment of the liver with a tissue ablation modality that combined
      electroporation with electrolysis (E2). Rat liver was treated with an E2 waveform
      and the tissue examined, 1 h, 3 h, 6 h and 24 h with: H&E, Masson Trichrome,
      TUNEL stains and Western blot. H&E and TUNEL stains have shown that cell death
      began to be evident 3 h and hepatocyte regeneration was seen 24 h after
      treatment. H&E and Masson trichrome have shown that the extracellular matrix and
      the large lumens, appeared intact after E2. Western blot has shown the following
      molecular events after E2: cleaved caspase 3-downgraded at 1 h, upgraded at 24 h
      (apoptosis); cleaved Caspase 1 and cleaved GSDMD-upgraded at 6 h (pyroptosis),
      RIP3-upgraded at 1 h, MLKL-upgraded at 3 h (necroptosis). The mechanism of cell
      death was possible initiated by necroptosis pathway. Pyroptosis pathway was also
      activated. The observation that cell death from E2 was by programed necrosis and
      the details on the temporal molecular pathways, may have value for the recent
      attempt to combine electroporation mediated ablation with immunological
      treatment, by demonstrating that the cell death from E2 involves an inflammatory
      response and by providing data that could be used to design the optimal timing
      for the injection of immunological adjuvants.

PMID- 30292930
TI  - Liquid crystals-based sensor for the detection of lithocholic acid coupled with
      competitive host-guest inclusion.
AB  - A simple, low-cost and label-free strategy for detecting lithocholic acid (LCA)
      was designed at the liquid crystals (LCs)/aqueous interface via competitive host
      guest inclusion. In this method, sodium dodecyl sulfate (SDS) was initially
      adsorbed on the fluid interface and induced LCs to adopt the homeotropic
      ordering. Inclusion complexation of SDS and beta-cyclodextrin (beta-CD) disturbed
      interaction between LCs and SDS and evoked LCs to keep a tilted alignment. When
      injecting LCA into the mixed solution of SDS and beta-CD, SDS excluded from the
      cavity of beta-CD by competitive host-guest inclusion and could be re-adsorbed at
      the LCs/aqueous interface, resulting in the orientational transition of LCs from
      tilted to homeotropic state. Correspondingly, a bright-to-dark optical response
      was observed under polarized optical microscope (POM). The as-prepared LCs-based
      sensor could detect LCA as low as about 2 MUM in aqueous solution. Moreover, the
      practicability of the approach was validated by monitoring the known amount of
      LCA in human urine. This work offers an appealing approach for the detection of
      LCA which has a great potentiality in clinical diagnosis.

PMID- 30292931
TI  - Hepatocyte culture on 3D porous scaffolds of PCL/PMCL.
AB  - The development of three-dimensional (3D) porous scaffolds for soft tissue
      engineering mainly focused on manipulation of scaffold properties with cell
      behaviors. By emulsion freeze-drying method, four types of porous scaffolds were
      prepared from amorphous poly(4-methy-epsilon-caprolactone) (PMCL) and semi
      crystalline poly(epsilon-caprolactone) (PCL) at different weight ratios, named as
      PMCL0, PMCL30, PMCL50 and PMCL70, respectively. Visual observation on cross
      sectional images of the scaffolds appeared as sponge-like materials with three
      dimensional and highly porous morphologies. However, the pore size, porosity and
      wettability of blends were not decreased linearly with increasing amorphous PMCL.
      Distinguished from PMCL30 or PMCL70, PMCL50 preserved intact PCL crystals
      distributed in amorphous matrix, resulting in the lowest Young's modulus (E) and
      relatively high wettability. From in vitro cell culture, it was observed that
      PMCL50 scaffold supported human induced hepatocytes (hiHeps) proliferation and
      function preservation best among all scaffolds. hiHeps on PMCL50 inclined to
      adopt fibroblastic morphology, whereas formed spheroidal morphology on PMCL0. It
      was suggested that our bare scaffolds with tailored properties have shown
      remarkable capability towards hiHep proliferation and function expression.

PMID- 30292932
TI  - Substrate topography interacts with substrate stiffness and culture time to
      regulate mechanical properties and smooth muscle differentiation of mesenchymal
      stem cells.
AB  - Substrate stiffness and topography are two powerful means by which mesenchymal
      stem cells (MSCs) activities can be modulated. The effects of substrate stiffness
      on the MSCs mechanical properties were investigated previously, however, the role
      of substrate topography in this regard is not yet well understood. Moreover, in
      vessel wall, these two physical cues act simultaneously to regulate cellular
      function, hence it is important to investigate their cooperative effects on
      cellular activity. Herein, we investigated the combined effects of substrate
      stiffness, substrate topography and culture time on the mechanical behavior of
      MSCs. The MSCs were cultured on the stiff and soft substrates with or without
      micro-grooved topography for 10 days and their viscoelastic properties and smooth
      muscle (SM) gene expression were investigated on days 2, 6 and 10. In general,
      substrate topography significantly interacted with substrate stiffness as well as
      culture time in the modulation of cell viscoelastic behavior and SM gene
      expression. The micro-grooved, stiff substrates resulted in the maximum cell
      stiffness and gene expression of alpha-actin and h1-calponin, and these values
      were detected to be minimum in the smooth, soft substrates. The findings can be
      helpful in the mechano-regulation of MSCs for vascular tissue engineering
      applications.

PMID- 30292933
TI  - Towards biomimics of cell membranes: Structural effect of phosphatidylinositol
      triphosphate (PIP3) on a lipid bilayer.
AB  - Phosphoinositide (PIP) lipids are anionic phospholipids playing a fundamental
      role for the activity of several transmembrane and soluble proteins. Among all,
      phosphoinositol-3',4',5'-trisphosphate (PIP3) is a secondary signaling messenger
      that regulates the function of proteins involved in cell growth and gene
      transcription. The present study aims to reveal the structure of PIP-containing
      lipid membranes, which so far has been little explored. For this purpose,
      supported lipid bilayers (SLBs) containing 1,2-dioleoyl-sn-glycero-3-phospho-(1'
      myo-inositol-3',4',5'-trisphosphate (DOPIP3) and 1-palmitoyl-2-oleoyl-sn-glycero
      3-phosphocholine (POPC) were used as mimics of biomembranes. Surface sensitive
      techniques, i.e. Quartz Crystal Microbalance with Dissipation monitoring (QCM-D),
      Atomic Force Microscopy (AFM) and Neutron Reflectometry (NR), provided detailed
      information on the formation of the SLB and the location of DOPIP3 in the lipid
      membrane. Specifically, QCM-D and AFM were used to identify the best condition
      for lipid deposition and to estimate the total bilayer thickness. On the other
      hand, NR was used to collect experimental structural data on the DOPIP3 location
      and orientation within the lipid membrane. The two bilayer leaflets showed the
      same DOPIP3 concentration, thus suggesting the formation of a symmetric bilayer.
      The headgroup layer thicknesses of the pure POPC and the mixed POPC/DOPIP3
      bilayer suggest that the DOPIP3-headgroups have a preferred orientation, which is
      not perpendicular to the membrane surface, but instead it is close to the
      surrounding lipid headgroups. These results support the proposed PIP3 tendency to
      interact with the other lipid headgroups as PC, so far exclusively suggested by
      MD simulations.

PMID- 30292934
TI  - Correspondence on: "Gas embolism as a potential cause of death by helium
      poisoning - Postmortem computed tomography changes in two cases of suicidal
      helium inhalation".

PMID- 30292935
TI  - An empirical cross-validation of denoising filters for PRNU extraction.
AB  - The present work is an empirical study to check the importance of widely used
      PRNU extraction de-noising filters at different stages of source camera
      identification procedure. The proposed work is unique in the sense that it gives
      an idea about the choice of the appropriate de-noising filters at the time of
      PRNU extraction for formation of unique identification pattern of digital camera
      and noise residue extraction of query image. Also in this work, we have suggested
      the best values of sigma (noise variance) for formation of unique identification
      pattern of digital camera and noise residue extraction of query image (based on
      empirical observations). This study has been performed to check that which part
      (camera unique identification pattern, noise residue, enhancement methods, and
      value of sigma) mostly dominates the performance of source camera identification.

PMID- 30292936
TI  - A multifactorial critical appraisal of substances found in drug facilitated
      sexual assault cases.
AB  - Drug-facilitated sexual assault (DFSA) is a sexual act in which the victim is
      unable to give or rescind consent due to intoxication with alcohol and/or drugs
      that have been self-administered (opportunistic DFSA) or covertly administered by
      the perpetrator (predatory DFSA). The drugs that are most commonly associated
      with DFSA are flunitrazepam and gamma-hydroxybutyric acid (GHB). They cause
      sedation and amnesia, are readily dissolved in beverages and are rapidly
      eliminated from the system. However, drugs such as amphetamine and cocaine, which
      are central nervous system (CNS) stimulants, have also been encountered in DFSA
      cases. This paper critically evaluates trend data from cohort studies,
      identifying drugs that have been detected in DFSA cases and reports on the
      differences in drugs used between opportunistic and predatory DFSA. This is the
      first time that a critical multifactorial review of drugs used in DFSA has been
      conducted. The pharmacology of each identified group of drugs is presented,
      showing why these compounds are of interest and used in the perpetration of DFSA.
      Furthermore, the pharmacology and mechanisms of action are described to explain
      how the drugs cause their effects. It is also apparent from this study that if
      meaningful data is to be exchanged between law enforcement agencies then it is
      necessary to agree on protocols for the collection of evidence and the drugs for
      which analysis should be performed and indeed on the analytical methods used.

PMID- 30292937
TI  - A comparative study of different laboratory storage conditions for enhanced DNA
      analysis of crime scene soil-blood mixed sample.
AB  - Crime scene investigation is an important step in the entire criminal
      investigation process because this is where evidence is gathered. Blood from the
      perpetrator or victim of a crime can be left at crime scenes or transferred to
      other materials such as clothing, knives and guns. Most often, this body fluid is
      contaminated with soil at outdoor crime scenes but this might be the only or the
      most important evidence in solving a crime. This work aimed at identifying the
      most appropriate method of storing crime scene soil-blood mixed sample prior to
      analysis at the laboratory. Human blood was mixed with soil and stored at three
      different storage conditions (i.e., Room temperature/25 degrees C, 4 degrees C
      and -20 degrees C). Samples stored at room temperature saw significant reduction
      in DNA concentration as storage time increased (P=0.001). Samples stored at 4
      degrees C saw a drastic decrease in DNA concentration just after two weeks of
      storage. By the eighth week of storage at 4 degrees C, there was no detectable
      DNA (P=0.000). Samples stored at -20 degrees C recorded no specific pattern in
      decrease or increase in DNA concentration for the entire 12week storage
      (P=0.324). There were full STR Profiles generated for room temperature stored
      samples and -20 degrees C stored samples throughout the study. There were full,
      partial and null Profiles generated for 4 degrees C stored samples depending on
      the sample storage duration. In conclusion, -20 degrees C was identified as the
      best storage condition for soil-blood mixed sample followed by room temperature
      and 4 degrees C, respectively.

PMID- 30292938
TI  - Corrigendum to "Nanoscaled red blood cells facilitate breast cancer treatment by
      combining photothermal/photodynamic therapy and chemotherapy" [Biomaterials 155C
      (2017) 25-40].

PMID- 30292939
TI  - A facile approach for development of a vaccine made of bacterial double-layered
      membrane vesicles (DMVs).
AB  - Bacterial infections cause acute and chronic diseases. Antimicrobial resistance
      and aging-related immune weakness remain challenging in therapy of infectious
      diseases. Vaccines are however an alternative to prevent bacterial infections.
      Here we report a facile method to rapidly generate bacterium-membrane-formed
      nanovesicles as a vaccine using nitrogen cavitation. The vaccine is comprised of
      double-layered membrane vesicles (DMVs) characterized by cryo-TEM, biochemistry
      and proteomics, showing DMVs possess the integrity of bacterial membrane and
      contain a wide range of membrane proteins required for vaccination. In the mouse
      sepsis model induced by Pseudomonas aeruginosa, we found that DMVs can improve
      mouse survival after mice were immunized with DMVs. The increased adaptive
      immunity and unique biodistribution of DMVs were responsible for enhanced
      protection of bacterial infection. Our studies demonstrate that this simple and
      innovative approach using nitrogen cavitation would be a promising technology for
      vaccine developments.

PMID- 30292941
TI  - Specific discrimination of gram-positive bacteria and direct visualization of its
      infection towards mammalian cells by a DPAN-based AIEgen.
AB  - The infections caused by gram-positive bacteria (G+) is a major threat to public
      health due to their high morbidity and mortality, and the identification of G+
      with high sensitivity and selectivity is urgently desirable. In this paper, a
      probe with aggregation-induced emission (AIE) characteristic is developed and
      used to discriminate G+ from other bacteria and fungus with excellent
      selectivity. Thanks for its AIE feature, this probe shows intense fluorescence
      when interacted with G+, and the signal can last for 24 h after incubating with
      S. aureus, which is benefit for long term tracing of translocation process with
      high contrast. Moreover, this probe can be used to visualize the infection
      processes of G+ towards mammalian cells, which provides valuable information for
      understanding the therapeutic mechanism.

PMID- 30292940
TI  - The effects of a functionally-graded scaffold and bone marrow-derived mononuclear
      cells on steroid-induced femoral head osteonecrosis.
AB  - Osteonecrosis of the femoral head (ONFH) is a debilitating disease that may
      progress to femoral head collapse and subsequently, degenerative arthritis.
      Although injection of bone marrow-derived mononuclear cells (BMMCs) is often
      performed with core decompression (CD) in the early stage of ONFH, these
      treatments are not always effective in prevention of disease progression and
      femoral head collapse. We previously described a novel 3D printed, customized
      functionally-graded scaffold (FGS) that improved bone growth in the femoral head
      after CD in a normal healthy rabbit, by providing structural and mechanical
      guidance. The present study demonstrates similar results of the FGS in a rabbit
      steroid-induced osteonecrosis model. Furthermore, the injection of BMMCs into the
      CD decreased the osteonecrotic area in the femoral head. Thus, the combination of
      FGS and BMMC provides a new therapy modality that may improve the outcome of CD
      for early stage of ONFH by providing both enhanced biological and biomechanical
      cues to promote bone regeneration in the osteonecrotic area.

PMID- 30292942
TI  - Nitric oxide as an all-rounder for enhanced photodynamic therapy: Hypoxia relief,
      glutathione depletion and reactive nitrogen species generation.
AB  - A glutathione (GSH)-sensitive supramolecular nitric oxide (NO) nanogenerator is
      developed as an all-rounder for enhanced photodynamic therapy (PDT). By
      integrating GSH-sensitive NO prodrug into the system via LEGO-like host-guest
      interaction, the nanocarrier could not only deplete intracellular GSH, but also
      relieve hypoxia at tumor sites through NO mediated blood vessel relaxation.
      Furthermore, reactive nitrogen species (RNS) with enhanced biocidal activity
      could be produced by the reaction between NO and reactive oxygen species (ROS),
      generated from alpha-cyclodextrin (alpha-CD) conjugated S-nitrosothiol and light
      activated chlorin e6 (Ce6) respectively. Due to multiple combined effects between
      NO and PDT, the NO acts as the loaded gunpowder inside a 'grenade', 'explosively'
      amplifying the therapeutic effects that the light responsive 'fuse' Ce6 could
      exert. The present work may well serve as an inspiration for future creative
      approaches of photodynamic cancer therapy.

PMID- 30292943
TI  - Corrigendum to "Let-7b ameliorates Crohn's disease-associated adherent-invasive E
      coli induced intestinal inflammation via modulating Toll-Like Receptor 4
      expression in intestinal epithelial cells" [Biochem. Pharmacol. 15 (2018) 196
      203].

PMID- 30292944
TI  - The mediating role of parenting behaviors in the relationship between early and
      late adolescent levels of anxiety: Specificity and informant effects.
AB  - INTRODUCTION: The role of parenting behavior is often highlighted in the
      development of anxiety in youth. However, previous reports are limited in terms
      of the specificity of relationships between different types of anxiety and
      parenting behaviors, informant effects on these relationships, and direction of
      effects. METHODS: This study investigates these questions using longitudinal data
      from 1350 Swedish adolescents and their parents. Adolescents' self-reports of six
      dimensions of anxiety and adolescents' and parents' reports of six dimensions of
      parenting behaviors were used in the analyses. Parallel multiple mediation models
      were employed to analyze specificity and informant effects within a reciprocal
      effects model. RESULTS: Overall, and irrespective of informant, this study found
      little support for a mediating role of parenting behaviors in the relationship
      between early and late adolescent levels of anxiety. Evidence for specificity
      within the parenting-anxiety relationship was scarce with specific mediating
      effects observed only for panic/agoraphobia and total anxiety through the
      parenting dimension of rejection. CONCLUSIONS: The findings of this study concern
      the un-conditional mediating role of parenting. Parenting behaviors may be more
      influential among some adolescents, depending on individual differences in other
      factors related to the development and course of adolescent anxiety. Thus,
      further research on moderating factors of the influence of parenting on
      adolescent anxiety is warranted.

PMID- 30292945
TI  - Homocysteine causes vascular endothelial dysfunction by disrupting endoplasmic
      reticulum redox homeostasis.
AB  - Endothelial dysfunction induced by hyperhomocysteinemia (HHcy) plays a critical
      role in vascular pathology. However, little is known about the role of
      endoplasmic reticulum (ER) redox homeostasis in HHcy-induced endothelial
      dysfunction. Here, we show that Hcy induces ER oxidoreductin-1alpha (Ero1alpha)
      expression with ER stress and inflammation in human umbilical vein endothelial
      cells and in the arteries of HHcy mice. Hcy upregulates Ero1alpha expression by
      promoting binding of hypoxia-inducible factor 1alpha to the ERO1A promoter.
      Notably, Hcy rather than other thiol agents markedly increases the GSH/GSSG ratio
      in the ER, therefore allosterically activating Ero1alpha to produce H2O2 and
      trigger ER oxidative stress. By contrast, the antioxidant pathway mediated by ER
      glutathione peroxidase 7 (GPx7) is downregulated in HHcy mice. Ero1alpha
      knockdown and GPx7 overexpression protect the endothelium from HHcy-induced ER
      oxidative stress and inflammation. Our work suggests that targeting ER redox
      homeostasis could be used as an intervention for HHcy-related vascular diseases.

PMID- 30292947
TI  - Comparison of 3-Tesla to 1.5-Tesla Magnetic Resonance Enterography to assess
      multifocal and multicentric bowel endometriosis: Results in routine practice.
AB  - STUDY OBJECTIVE: To compare 1.5-Tesla (1.5 T) to 3-Tesla (3 T) Magnetic resonance
      enterography (MRE) in assessing multifocal (multiple lesions affecting the same
      segment) and multicentric (multiple lesions affecting several digestive segments)
      bowel endometriosis in patients with suspected-colorectal endometriosis, in
      routine practice. STUDY DESIGN: We conducted a retrospective, comparative study
      in Tenon University Hospital, Paris, France. We included patients scheduled for
      colorectal resection from April 2014 to February 2018. All patients underwent 1.5
      T or 3 T MRE before surgery and endometriosis lesions were confirmed by surgery.
      The diagnostic performance of 1.5 T and 3 T MRE was evaluated by sensitivity,
      specificity, positive and negative predictive values (PPV and NPV), accuracy,
      positive and negative likelihood ratios (LR) and area under the curve of receiver
      operating curves (AUC ROC). RESULTS: Ninety-eight patients were included. Fifty
      two (53%) patients presented unifocal lesions, 31 (32%) multifocal lesions, and
      23 (24%) multicentric lesions. In assessment of multifocal lesions, the
      sensitivity, specificity, positive and negative LRs were 0.57 (12/21), 0.89
      (23/26), 4.95 and 0.58 for 1.5 T MRE, and 0.10 (1/10), 0.95 (39/41), 2.05 and
      0.95 for 3 T MRE. For the diagnosis of multicentric lesions, 1.5 T MRE showed
      sensitivity, specificity, positive and negative LRs of 0.46 (5 of 11), 0.92 (33
      of 36), 5.45 and 0.60 respectively and 3 T MRE showed sensitivity, specificity,
      and negative LRs of 0.33 (4/12), 1.00 (39/39), and 0.67, respectively. 1.5 T MRE
      was more accurate than 3 T MRE for diagnosing multifocal lesions (p = 0.02), but
      there was no difference for multicentric lesion assessment (p = 0.66).
      CONCLUSION: In routine conditions, 3 T MRE and 1.5 T MRE are of similar low
      performance for diagnosing multifocal and multicentric bowel endometriosis.

PMID- 30292946
TI  - The enzyme activity of histone deacetylase 8 is modulated by a redox-switch.
AB  - Enzymes from the histone deacetylase (HDAC) family are highly regulated by
      different mechanisms. However, only very limited knowledge exists about the
      regulation of HDAC8, an established target in multiple types of cancer. A
      previous dedicated study of HDAC class I enzymes identified no redox-sensitive
      cysteinyl thiol in HDAC8. This is in contrast to the observation that HDAC8
      preparations show different enzyme activities depending on the addition of
      reducing agents. In the light of the importance of HDAC8 in tumorigenesis a
      possible regulation by redox signaling was investigated using biochemical and
      biophysical methods combined with site directed mutagenesis. The occurrence of a
      characteristic disulfide bond under oxidizing conditions is associated with a
      complete but reversible loss of enzyme activity. Cysteines 102 and 153 are the
      integral components of the redox-switch. A possible regulation of HDAC8 by redox
      signal transduction is suggested by the observed relationship between inhibition
      of reactive oxygen species generating NOX and concomitant increased HDAC8
      activity in neuroblastoma tumor cells. The slow kinetics for direct oxidation of
      HDAC8 by hydrogen peroxide suggests that transmitters of oxidative equivalents
      are required to transfer the H2O2 signal to HDAC8.

PMID- 30292948
TI  - A simple and fast HPLC-MS/MS method for simultaneous determination of direct oral
      anticoagulants apixaban, dabigatran, rivaroxaban in human plasma.
AB  - Direct Oral Anticoagulants (DOACs) available for the treatment and prevention of
      thromboembolic diseases include dabigatran, a direct thrombin (IIa) inhibitor,
      and apixaban, edoxaban and rivaroxaban, which are direct inhibitors of Stuart
      factor (Xa). DOACs have a different pharmacokinetic and pharmacodynamics
      profiles, with less probable drug-drug interactions than vitamin K antagonists.
      They do not require systematic therapeutic monitoring except in specific clinical
      situations such as emergency procedures or drug non-compliance. Furthermore,
      anticoagulant effects of DOACs could be impacted by renal impairment, drug-drug
      interactions, food interactions, or pharmacogenetic variability. In this context,
      we developed a method for simultaneous determination of dabigatran, rivaroxaban
      and apixaban in human plasma using high performance liquid chromatography coupled
      with a mass spectrometry assay and applied it to 26 patient samples. Our method
      presents a total run time of 5 min and extends from 25 to 1000 MUg/L for apixaban
      and dabigatran; and from 5 to 1000 MUg/L for rivaroxaban. Intra- and inter-assay
      accuracy were between -22.3 and 25.4%; and - 23.7 and 3.8%, respectively.
      Precision at low and high concentrations were below 17.5%. Frozen samples were
      stable up to 3 months. No significant cross-contamination was observed. In
      conclusion, our assay can be used during clinical studies and in daily routine
      practice for the management of specific clinical situations at reasonable cost.

PMID- 30292949
TI  - Performance of 3-[4-(bromomethyl)phenyl]-7-(diethylamino) coumarin as a
      derivatization reagent for the analysis of medium and long chain fatty acids
      using HPLC with LIF detection.
AB  - Knowledge of the profile of fatty acids, including the profile of long chain
      fatty acids, is an important parameter for many areas like human health, food
      sciences, and the study of gene expression in plant tissues, among others.
      Moreover, very long chain fatty acids occur at low concentrations in many
      biological samples. The 3-[4-(bromomethyl)phenyl]-7-(diethylamino)coumarin (MPAC
      Br) reagent is an improved version of the coumarin bromomethyl-type reagents,
      used for the fluorescent labeling of carboxylic acids in a variety of sample
      types. Derivatization reactions are always a matter of concern in routine
      analyses, as they are seen as a time demanding step and a source of errors in
      analytical chemistry. MPAC-Br is studied in the present work, including the
      robustness of its derivatization reaction, the stability of its derivatives, the
      limits of its detection and the repeatability of its results. An optimized
      version of its protocol was applied to determine the content and profiles of both
      medium and long chain fatty acids in eight samples of oils and fats. It was shown
      that the proposed derivatization reaction is a reliable, robust, fast and
      convenient method for the analysis of these compounds.

PMID- 30292950
TI  - Development of a parallel microbore hollow fiber enzyme reactor platform for
      online 18O-labeling: Application to lectin-specific lung cancer N-glycoproteome.
AB  - We introduce a simple online 18O-labeling protocol for protein samples that uses
      a parallelizing microbore hollow fiber enzyme reactor (mHFER) as an alternative
      tool for online proteolytic digestion. Online 18O-labeling is performed by
      separately attaching two mHFERs in parallel to a 10-port switching valve with a
      high-pressure syringe pump and two syringes containing 16O- or 18O-water. 16O
      /18O-labeled peptides are formed in this manner and simultaneously analyzed
      online using nanoflow liquid chromatography-tandem mass spectrometry (nLC-MS/MS)
      without any residual trypsin activity. The usefulness of a parallel mHFER
      platform (P-mHFER) in 18O-labeling was tested using both cytochrome C and alpha-1
      acid-glycoprotein to verify the incorporation level of two 18O atoms into tryptic
      peptides and to provide a quantitative assessment with varied mixing ratios.
      Additionally, our 18O-labeling approach was used to study the serum N
      glycoproteome from lung cancer patients and controls to evaluate the
      applicability of lectin-based quantitative N-glycoproteomics. We successfully
      quantified 76 peptides (from 62 N-glycoproteins). Nineteen of these peptides from
      lung cancer serum were up-/down-regulated at least 2.5-fold compared to controls.
      As a result, the P-mHFER-based online 18O-labeling platform presented here can be
      a simple and reproducible way to allow quantitative proteomic analysis of diverse
      proteome samples.

PMID- 30292951
TI  - Direct recovery of malate dehydrogenase from highly turbid yeast cell homogenate
      using dye-ligand affinity chromatography in stirred fluidized bed.
AB  - Dye-ligand affinity chromatography in a stirred fluidized bed has been developed
      for the rapid recovery of malate dehydrogenase (MDH) from highly turbid baker's
      yeast cell homogenate in a single step. The most suitable dye, namely Reactive
      Orange 4, in its optimal immobilized concentration of 8.78 mg/mL was immobilized
      onto high-density STREAMLINE matrix. To further examine optimal adsorption and
      elution conditions, the enzyme recovery operation was carried out using
      unclarified cell homogenates in stirred fluidized bed system. Aiming to develop a
      non-specific eluent, namely NaCl, to effectively elute the MDH adsorbed, direct
      recovery of MDH from highly turbid cell homogenate (50% w/v) in a stirred
      fluidized bed adsorption system was performed. The proposed system successfully
      achieved a recovery yield of 73.6% and a purification factor of 73.5 in a single
      step by using 0.6 M NaCl as an eluent at a high liquid velocity of 200 cm/h.

PMID- 30292952
TI  - Screening bioactive compounds with multi-targets from Rhodiola crenulata by a
      single column containing co-immobilized beta2-adrenergic receptor and voltage
      dependent anion channel isoform 1.
AB  - The pursuit of drugs having improved therapeutic efficacy necessitates increasing
      research on new assays for screening bioactive compounds with multi-targets. This
      work synthesized a chromatographic stationary phase containing co-immobilized
      beta2-adrenergic receptor (beta2-AR) and voltage dependent anion channel isoform
      1 (VDAC-1) to achieve such purpose. Specific ligands of the two receptors (e.g.
      salbutamol, methoxyphenamine, ATP and NADH) were utilized to characterize the
      specificity and bioactivity of the column. Validated application of the
      stationary phase was performed by screening multi-target compounds of Rhodiola
      crenulata using high performance affinity chromatography coupled with ESI-Q-TOF
      MS. By zonal elution, we identified salidroside as a bioactive compound
      simultaneously binding to beta2-AR and VDAC-1. The compound exhibited the binding
      sites of 1.0 * 10-7 and 4.0 * 10-7 M on the beta2-AR and VDAC-1. On these sites,
      the association constants were calculated to be 3.3 * 104 and 1.0 * 104 M-1.
      Molecular docking indicated that the binding of salidroside to the two receptors
      occurred on Ser169 and Phe255of beta2-AR, and the channel wall of VDAC-1. Taking
      together, we concluded that the column containing co-immobilized receptors has
      potential for screening bioactive compounds with multi-targets from complex
      matrices including traditional Chinese medicines.

PMID- 30292953
TI  - Does articulatory rehearsal help immediate serial recall?
AB  - Articulatory rehearsal is assumed to benefit verbal working memory. Yet, there is
      no experimental evidence supporting a causal link between rehearsal and serial
      order memory, which is one of the hallmarks of working memory functioning. Across
      four experiments, we tested the hypothesis that rehearsal improves working memory
      by asking participants to rehearse overtly and by instructing different rehearsal
      schedules. In Experiments 1a, 1b, and 2, we compared an instructed cumulative
      rehearsal condition against a free-rehearsal condition. The instruction increased
      the prevalence of cumulative rehearsal, but recall performance remained unchanged
      or decreased compared to the free-rehearsal baseline. Experiment 2 also tested
      the impact of a fixed rehearsal instruction; this condition yielded substantial
      performance costs compared to the baseline. Experiment 3 tested whether
      rehearsals (according to an experimenter-controlled protocol) are beneficial
      compared to a matched articulatory suppression condition that blocked rehearsals
      of the memoranda. Again, rehearsing the memoranda yielded no benefit compared to
      articulatory suppression. In sum, our results are incompatible with the notion
      that rehearsal is beneficial to working memory.

PMID- 30292954
TI  - New phenolic halogenated disinfection byproducts in simulated chlorinated
      drinking water: Identification, decomposition, and control by ozone-activated
      carbon treatment.
AB  - Recently, 13 new phenolic halogenated disinfection byproducts (DBPs) were
      discovered and confirmed in chlorinated drinking water using ultra performance
      liquid chromatography/electrospray ionization-triple quadrupole mass spectrometry
      (UPLC/ESI-tqMS), which have been attracting a growing concern due to their higher
      chronic cytotoxicity, developmental toxicity, and growth inhibition compared with
      commonly known aliphatic DBPs. In this study, another 12 new phenolic halogenated
      DBPs were detected and identified in simulated chlorinated drinking water
      samples, including two monohalo-4-hydroxybenzaldehydes, two monohalo-4
      hydroxybenzoic acids, three monohalo-salicylic acids, and five mono/di/trihalo
      phenols. Decomposition mechanisms of these new phenolic halogenated DBPs during
      chlorination were speculated and partially verified by identifying intermediate
      products. These new DBPs could undergo hydrolysis, halogenation, substitution,
      addition, decarboxylation, and rearrangement reactions to form a series of
      decomposition products, including dihaloacetic acids, 2-halomaleic acids, and a
      group of new heterocyclic DBPs (trihalo-hydroxy-cyclopentene-diones). A bench
      scale ozone-granular activated carbon (GAC) treatment unit was designed and set
      up in the lab. It was found that ozonation and GAC filtration were effective in
      reducing dissolved organic carbon levels and aromaticity (DBP precursors) of
      simulated raw water samples, and thus were effective in decreasing the
      concentrations of these new phenolic DBPs by 82.5% and 88.6%, respectively.
      Furthermore, four different treatment scenarios (i.e., ozonation, GAC filtration,
      ozonation followed by GAC filtration, and GAC filtration followed by ozonation)
      were evaluated and compared. Results showed that ozonation followed by GAC
      filtration was most effective in precursor removal and could decrease the level
      of these new phenolic DBPs by up to 97.3%.

PMID- 30292955
TI  - Acidification and recovery of phosphorus from digested and non-digested sludge.
AB  - Acidification was used to dissolve phosphorus from digested and non-digested
      sludge from five wastewater treatment plants in order to make phosphorus
      accessible for subsequent recovery. More phosphorus was dissolved from digested
      sludge (up to 80%), with respect to non-digested sludge (~25%) and the highest
      release was observed at pH 2. The acid consumption for digested sludge was higher
      than for non-digested sludge due to the presence of the bicarbonate buffer
      system, thus CO2 stripping increased the acid consumption. In all the
      experiments, the sludge was exposed to acid for 1 h. For the five tested sludge
      types, 60-100 mmol o-P was released per added mol H2SO4. It was mainly iron and
      calcium compounds that accounts for the phosphorus release at low pH. The release
      of heavy metals was in general low (<30%) for all the wastewater treatment plant,
      as Zn, Cd and Ni showed the most critical release after acidification of non
      digested sludge.

PMID- 30292956
TI  - Determination of radiocesium depth profile by unfolding method with imaging
      plate.
AB  - Radiocesium depth profiles in Fukushima soil cores were derived with an unfolding
      method by using an imaging plate with a response matrix for 134Cs, 137Cs, and 40K
      radionuclides calculated by a PHITS simulation. The unfolded depth profiles were
      validated by comparison with profiles measured with a Ge detector. The unfolded
      depth profiles agreed well with those measured by the Ge detector. The depth
      profiles obtained were obtained with a 1 mm depth bin width and are useful for
      estimating the migration of radiocesium in soil.

PMID- 30292957
TI  - Simulating the radial dose distribution for charged particles in water medium by
      a semi-empirical model: An analytical approach.
AB  - A computational semi-empirical model based on electronic radiation damage to
      medium has been presented to simulate the radial dose distribution. An analytical
      approach was used to calculate the deposited energy in water per unit mass within
      a cylindrical shell of unit length around the ion path at a radial distance
      between r and r + dr, the so-called radial dose distribution, RDD. Detail steps
      were given and the final radial dose integration over the electron range between
      Rmin and Rmax was solved numerically using the Mid-Point Method. A validation for
      the present model was presented by integrating the RDD over all possible radial
      distances, r to yield the tabulated LET of the ion. The validation was presented
      for a range of proton ions of different energies. The RDD for heavy charged
      particles of proton, alpha, Carbon and Oxygen ions of different energies in
      liquid water were obtained. Good agreement between the present model and
      experimental, theoretical, and Monte Carlo (Geant4-DNA) data were obtained for
      all ions under investigations.

PMID- 30292958
TI  - In-vivo assessment of osseous versus non-osseous transmission pathways of
      vibratory stimuli applied to the bone and the dura in humans.
AB  - BACKGROUND: Bone conduction (BC) is an alternative to air conduction (AC) for
      stimulation of the inner ear. Stimulation for BC can occur directly on the skull
      bone, on the skin covering the skull bone, or on soft tissue (i.e., eye, dura).
      All of these stimuli can elicit otoacoustic emissions (OAE). This study aims to
      compare OAEs generated by different combinations of stimuli in live humans,
      including direct stimulation of the intracranial contents via the dura, measured
      intraoperatively. METHODS: Measurements were performed in five normal-hearing
      ears of subjects undergoing a neurosurgical intervention with craniotomy in
      general anesthesia. Distortion product OAEs (DPOAEs) were measured for f2 at 0.7,
      1, 2, 3, 4, and 6 kHz with a constant ratio of the primary frequencies (f2/f1) of
      1.22. Sound pressure L1 was held constant at 65 dB SPL, while L2 was decreased in
      10 dB steps from 70 to 30 dB SPL. A DPOAE was considered significant when its
      level was >=6 dB above the noise floor. Emissions were generated sequentially
      with different modes of stimulation: 1) pre-operatively in the awake subject by
      two air-conducted tones (AC-AC); 2) within the same session preoperatively by one
      air- and one bone-conducted tone on the skin-covered temporal bone as in
      audiometry (AC-BC); 3) intra-operatively by one air-conducted tone and one bone
      vibrator tone applied directly on the dura (AC-DC). A modified bone vibrator
      (Bonebridge; MED-EL, Innsbruck, Austria) was used for BC stimulation on the dura
      or skin-covered mastoid. Its equivalent perceived SPL was calibrated
      preoperatively for each individual by psychoacoustically comparing the level of a
      BC tone presented to the temporal region to an AC tone at the same frequency.
      Simultaneously with the DPOAEs, vibrations at the teeth were measured with an
      accelerometer attached using a custom-made holder. RESULTS: It was possible to
      record DPOAEs for all three stimulation modes. For AC-DC, DPOAEs were not
      detected above the noise floor below 2 kHz but were detectable at the higher
      frequencies. The best response was measured at or above 2 kHz with L2 = 60 dB
      SPL. The acceleration measured at the teeth for stimulation on the dura was lower
      than that for stimulation on the bone, especially below 3 kHz. CONCLUSION: We
      demonstrate a proof-of-concept comparison of DPOAEs and teeth acceleration levels
      elicited by a bone vibrator placed either against the skin-covered temporal bone,
      as in audiometry, or directly against the dura mater in patients undergoing a
      craniotomy. It was demonstrated that DPOAEs could be elicited via non-osseous
      pathways within the skull contents and that the required measurements could be
      performed intra-operatively.

PMID- 30292959
TI  - Cortical correlates of speech intelligibility measured using functional near
      infrared spectroscopy (fNIRS).
AB  - Functional neuroimaging has identified that the temporal, frontal and parietal
      cortex support core aspects of speech processing. An objective measure of speech
      intelligibility based on cortical activation in these brain regions would be
      extremely useful to speech communication and hearing device applications. In the
      current study, we used noise-vocoded speech to examine cortical correlates of
      speech intelligibility in normally-hearing listeners using functional near
      infrared spectroscopy (fNIRS), a non-invasive, neuroimaging technique that is
      fully-compatible with hearing devices, including cochlear implants. In twenty
      three normally-hearing adults we measured (1) activation in superior temporal,
      inferior frontal and inferior parietal cortex bilaterally and (2) behavioural
      speech intelligibility. Listeners heard noise-vocoded sentences targeting five
      equally spaced levels of intelligibility between 0 and 100% correct. Activation
      in superior temporal regions increased linearly with intelligibility. This
      relationship appears to have been driven in part by changing acoustic properties
      across stimulation conditions, rather than solely by intelligibility per se.
      Superior temporal activation was also predictive of individual differences in
      intelligibility in a challenging listening condition. Beyond superior temporal
      cortex, we identified regions in which activation varied non-linearly with
      intelligibility. For example, in left inferior frontal cortex, activation peaked
      in response to heavily degraded, yet still somewhat intelligible, speech.
      Activation in this region was linearly related to response time on a simultaneous
      behavioural task, suggesting it may contribute to decision making. Our results
      indicate that fNIRS has the potential to provide an objective measure of speech
      intelligibility in normally-hearing listeners. Should these results be found to
      apply similarly in the case of individuals listening through a cochlear implant,
      fNIRS would demonstrate potential for a clinically useful measure not only of
      speech intelligibility, but also of listening effort.

PMID- 30292960
TI  - Role of nesfatin-1 in anxiety, depression and the response to stress.
AB  - Nesfatin-1 has been discovered a decade ago and since then drawn a lot of
      attention. The initially proposed anorexigenic effect was followed by the
      description of several other involvements such as a role in gastrointestinal
      motility, glucose homeostasis, cardiovascular functions and thermoregulation
      giving rise to a pleiotropic action of this peptide. The recent years witnessed
      mounting evidence on the involvement of nesfatin-1 in emotional processes as
      well. The present review will describe the peptide's relations to anxiety,
      depressiveness and stress in animal models and humans and also discuss existing
      gaps in knowledge in order to stimulate further research.

PMID- 30292961
TI  - Stability of diurnal cortisol measures across days, weeks, and years across
      middle childhood and early adolescence: Exploring the role of age, pubertal
      development, and sex.
AB  - Effective regulation of the hypothalamic-pituitary-adrenal axis (HPA-axis) has
      been linked to numerous health outcomes. Within-person variation in diurnal
      measures of HPA-axis regulation assessed over days, months, and years can range
      between 50-73% of total variation. In this study of 59 youth (ages 8-13), we
      quantified the stability of the cortisol awakening response (CAR), the diurnal
      slope, and tonic cortisol concentrations at waking and bedtime across 8 days (2
      sets of 4 consecutive days separated by 3 weeks), 3 weeks, and 3 years. We then
      compared the stability of these indices across three key developmental factors:
      age, pubertal status, and sex. Youth provided 4 saliva samples per day (waking,
      30 min post-waking, before dinner, and before bedtime) for 4 consecutive days
      during the 3rd week of an ongoing 8-week daily diary study. Youth repeated this
      same sampling procedure 3 weeks and 3 years later. Using multi-level modeling, we
      computed the amount of variance in diurnal HPA-axis regulation that was accounted
      for by nesting an individual's diurnal cortisol indices within days, weeks, or
      years. Across days, diurnal slope was the most stable index, whereas waking
      cortisol and CAR were the least stable. All indices except bedtime cortisol were
      similarly stable when measured across weeks, and all indices were uniformly
      stable when measured across 3 years. Boys, younger participants, and youth
      earlier in their pubertal development at study enrollment exhibited greater HPA
      axis stability overall compared with females and older, more physically mature
      participants. We conclude that important within- and between-subjects questions
      can be answered about health and human development by studying HPA-axis
      regulation, and selection of the index of interest should be determined in part
      by its psychometric characteristics. To this end, we propose a decision tree to
      guide study design for research in pediatric samples by longitudinal timeframe
      and sample characteristics.

PMID- 30292962
TI  - To trust, or not to trust? Individual differences in physiological reactivity
      predict trust under acute stress.
AB  - The stress response represents an evolutionarily ancient array of biological
      responses to challenge or threat that facilitate survival by promoting adaptive
      behaviors. 'Adaptive' in the evolutionary sense, however, does not easily
      translate to explain stress' effect on human decisions. Much research
      demonstrates that acute stress alters decision-making, but outcomes are obscured
      by a range of methodological factors. Further, less is known about how stress
      affects decision-making in social contexts in which people so often act. This is
      of great importance in today's increasingly complex social environment, replete
      with potential stressors, where cooperation and trust are critical. Here the aim
      was to explore acute stress' effect on prosocial decision-making, while also
      controlling for methodological factors that may contribute to varied research
      outcomes. Ninety-six participants were exposed between-subjects to acute
      stressors with or without a significant social evaluative component, or a control
      procedure, after which they performed a variant of the Trust Game (a social
      decision-making task requiring cooperation and trust with a 'partner'). Task
      performance occurred at different times with respect to exposure to examine the
      roles of temporally distinct biological stress pathways. Overall acute stress was
      associated with reduced trust, but a more complex pattern emerged when accounting
      for individual differences in physiological stress responses via multivariate
      analysis. In keeping with the complexity of stress itself, acute stress may
      enhance or reduce propensity to trust based on an individual's unique pattern of
      physiological reactivity.

PMID- 30292963
TI  - Characterization of dog serum virome from Northeastern Brazil.
AB  - Domestic dogs share habitats with human, a fact that makes them a potential
      source of zoonotic viruses. Moreover, knowledge regarding possible bloodborne
      pathogens is important due to the increasing application of blood transfusion in
      dogs. In the present study, we evaluated the serum virome of 520 dogs using
      throughput sequencing (HTS). The serum samples were pooled and sequenced using an
      Illumina MiSeq platform. Our unbiased method identified prevalent canine
      pathogens as canine protoparvovirus 1 (canine parvovirus 2), undersearched agents
      as canine bocaparvovirus 1 (minute virus of canines) and canine circovirus,
      circular viruses closely related to viruses recently found in human samples, and
      new parvovirus and anelloviruses. The dog virome described in the present work
      furthers the knowledge concerning the viral population in domestic animals. The
      present data includes information regarding viral agents that are potentially
      transmitted through blood transfusion among dogs.

PMID- 30292964
TI  - Posttubercular syringomyelia in HIV-infected patients: A report of 10 cases and
      literature review.
AB  - OBJECTIVES: To describe the clinical presentation, spinal magnetic resonance
      imaging (MRI) findings and outcome of HIV-infected patients with tuberculosis
      (TB)-associated syringomyelia and to compare these findings between all HIV
      infected and -uninfected cases published in the literature. METHODS: A
      retrospective observational study conducted over a 12.5-year period at a public
      sector referral hospital in South Africa. HIV-infected adults with neurological
      TB in whom MRI confirmed a syrinx were included. We searched PubMed to identify
      all published syringomyelia cases. RESULTS: Ten patients were enrolled.
      Syringomyelia complicated neurological TB within four years of initial diagnosis
      in all patients (median: 21 months, range: 0-39) after initial diagnosis. Six
      patients were treated conservatively (TB treatment = 5, no treatment = 1); four
      improved, but only one was ambulant during follow-up. Four patients underwent
      syringoperitoneal shunting; three improved and one died three months later. Our
      literature review identified 50 additional cases (HIV-infected = 2, HIV
      uninfected = 9, HIV status not documented = 39 [presumed HIV-uninfected]).
      Clinical and imaging findings and outcomes were similar between HIV-infected and 
      uninfected cases, except for time of presentation following neurological TB
      diagnosis, which was delayed (>4 years) in 46% of HIV-uninfected cases, compared
      to 8% of HIV-infected cases. Conclusions Syringomyelia is a disabling
      complication of neurological TB that usually presents early after neurological TB
      diagnosis in HIV coinfected patients.

PMID- 30292965
TI  - Mitochondrial therapeutic interventions in Alzheimer's disease.
AB  - Alzheimer's Disease (AD) is one of the most common age-related neurodegenerative
      diseases in the developed world. Treatment of AD is particularly challenging as
      the drug must overcome the blood brain barrier (BBB) before it can reach its
      target. Mitochondria are recognized as one of the most important targets for
      neurological drugs as the organelle is known to play a critical role in diverse
      cellular processes such as energy production and apoptosis regulation.
      Mitochondrial targeting was originally developed to study mitochondrial
      dysfunction and the organelles interaction with other sub-cellular organelles.
      The purpose of this review is to provide an overview of mitochondrial dysfunction
      and its role in late onset AD pathology. We then highlight recent antioxidant and
      enzymatic treatments used to alleviate mitochondrial dysfunction. Finally, we
      describe current applications of targeted mitochondrial delivery in the treatment
      of AD.

PMID- 30292967
TI  - Brain modelling in the framework of anisotropic hyperelasticity with time
      fractional damage evolution governed by the Caputo-Almeida fractional derivative.
AB  - In this paper the human brain tissue constitutive model for monotonic loading is
      developed. The model in this work is based on the anisotropic hyperelasticity
      assumption (the transversely isotropic case) together with modelling of the
      evolving load-carrying capacity (scalar damage) whose change is governed by the
      Caputo-Almeida fractional derivative. This allows the brain constitutive law to
      include the memory during progressive damage, due to the characteristic time
      length scale which is an inherent attribute of the fractional operator.
      Furthermore, the rate dependence of the overall brain tissue model is included as
      well. The theoretical model is finally calibrated and validated with a set of
      experimental data.

PMID- 30292966
TI  - Incidence of dementia in patients with adult-onset epilepsy of unknown causes.

PMID- 30292968
TI  - One-year mortality of patients admitted to the intensive care unit after in
      hospital cardiac arrest: a retrospective study.
AB  - PURPOSE: Little is known about long-term survival after In-Hospital Cardiac
      Arrest (IHCA). The purpose of this study is to report the one-year survival of
      patients after IHCA and to identify predicting factors. METHODS: Single-center
      retrospective study of all adult in-hospital CPR attempts conducted between 2003
      and 2014 in a tertiary teaching hospital. Demographic and clinical variables of
      patients were obtained at 24 h pre-arrest, during CPR and post-CPR. All patients
      were tracked one year after discharge from hospital. RESULTS: CPR was performed
      for IHCA on 417 patients. Return of spontaneous circulation (ROSC) was achieved
      in 283 (68%) patients, 234 were admitted to ICU. Overall, 95 (23%) patients
      survived one year after discharge, The survival rate of patients who were
      admitted to ICU after IHCA was 38% (89/234) at hospital discharge and 26%
      (61/234) at one year. Univariate analysis showed numerous variables are
      associated with one-year survival, for example comorbidity index and time to
      ROSC. DISCUSSION: One-year survival of patients admitted to the ICU after IHCA
      was 26%. Severity of disease pre-arrest and at ICU-admission could prove useful
      in prognostication. No multivariate model could be constructed and large
      prospective studies are needed to elicit the role of pre-arrest factors on
      survival.

PMID- 30292969
TI  - Diabetes progression and alterations in gut bacterial translocation: prevention
      by diet supplementation with human milk in NOD mice.
AB  - Impaired intestinal barrier function occurs before type 1 diabetes (T1D) onset
      with a possible contribution of microbial translocation. Breastfeeding is
      associated with enhanced mucosal intestinal integrity and T1D protection. Our aim
      was to study the potential of human milk (HM) to prevent diabetes onset and
      modulate the translocation of gut bacteria susceptible to breastfeeding or
      associated to diabetes onset. We show that HM intake can prevent T1D in nonobese
      diabetic mice independently of bifidobacteria colonization. Prior to diabetes
      onset, HM mice harbored splenic bacterial counts and plasma lipopolysaccharides
      level similar to control mice but exhibited a reduced expansion of Anaerotruncus
      sp. in pancreas and Lactobacillus johnsonii and Barnesiella in Peyer's patches
      (PP). Surprisingly, pancreas and PP bacterial expansion did not correlate with
      their own gut localization but with ileal Escherichia coli and cecal HM
      susceptible bacteria (the promoted L. murinus and Bacteroides vulgatus, and the
      repressed B. fragilis and E. coli), respectively. Besides, higher colonic B.
      vulgatus counts induced by HM intake were associated with low islet infiltration
      and pancreatic E. coli expansion. On another hand, splenic dendritic cells (DCs)
      were identified as negative covariate of PP Barnesiella, suggesting a possible HM
      contribution to preserving splenic DCs through the reduction of Barnesiella
      translocation. Fecal B. vulgatus also negatively correlated with PP Barnesiella
      expansion, indicating that the mouse coprophagic behavior likely added to HM
      effect. Our findings provide evidence that HM has a multilevel impact and
      cooperates with some gut bacteria for controlling bacterial translocation at the
      earliest stage of insulitis.

PMID- 30292970
TI  - Pb (II) bioavailability to algae (Chlorella pyrenoidosa) in relation to its
      complexation with humic acids of different molecular weight.
AB  - Humic acid (HA) has a major influence on the environmental fate of metal ions due
      to its heterogeneity in chemical compositions, structure and functional groups.
      In this study, we investigated the effect of humic acid (HA) with different
      molecular weight (Mw) on the bioavailability of Pb for a representative algae
      Chlorella pyrenoidosa. The results showed that HA with larger Mw had stronger
      inhibitory effects on the bioavailability of Pb to algae, and the biosorption
      capacity of Pb decreased with increasing Mw, which is in accordance with the
      variations of complexation capacities of Pb for HA fraction. In addition, we
      found that HA with Mw lower than 10 kDa could increase the biosorption capacity
      of Pb. The considerable differences among the Mw fractions on Pb biosorption were
      mainly attributed to their properties and corresponding complexation capacities.
      Phenolic groups were responsible for the variations of binding capacities among
      different Mw fractions, and it could also better explain the bioaccumulation of
      Pb to the membranes of algae. By using NICA-Donnan model, we found that over 60%
      of Pb ions were bound by HAs through specific binding, and the formation of Pb
      HAs complex were non-bioavailable to algae, which was proved by the considerably
      decreasing percentage of internalized Pb. This study provided further insight
      into the bioavailability of Pb to algae as influenced by the complexation of HA
      with metal ion such as Pb.

PMID- 30292971
TI  - Exogenous foliar application of fulvic acid alleviate cadmium toxicity in lettuce
      (Lactuca sativa L.).
AB  - It was reported that fulvic acid (FA) has a positive effect on enhancing plant
      tolerance to various environmental stresses, including salinity stress and
      drought stress and so on. However, there is little study regarding the effects of
      FA on plants in response to heavy metal stress. Hence, the objective of this
      study was to investigate the potential effects of fulvic acid (FA) on cadmium
      (Cd) toxicity alleviation in lettuce seedlings. Our results showed that
      application of 0.5 g/L FA significantly mitigate Cd-induced toxic symptoms in
      lettuce seedlings. Cd stress triggered plant growth inhibition, photosynthetic
      pigment reduction, destruction of the photosynthesis apparatus, reactive oxygen
      species (ROS) accumulation, and nutrient elemental imbalance. We observed that FA
      promoted the growth in lettuce under Cd stress, mainly reflected in those
      alterations that the increase of biomass, chlorophyll content and photosynthesis
      capacity and reduction of the Cd content and lipid peroxidation in plant tissue.
      Foliar spraying of FA significantly alleviated these detrimental symptoms and
      facilitated nutrient element translocation from root to shoot, particularly the
      absorption of elements involved in photosynthesis, including iron (Fe), zinc
      (Zn), and manganese (Mn). In summary, foliar application of FA conferred Cd
      toxicity tolerance to lettuce by increasing ROS-scavenging capacity, inhibiting
      Cd uptake and the transport of elemental nutrients to shoots, which in turn
      protected the photosynthetic apparatus and promoted plant growth.

PMID- 30292972
TI  - Toxicity assay of lanthanum and cerium in solutions and soil.
AB  - Lanthanum (La) and cerium (Ce) are one of the most abundant rare earth elements
      (REEs). In spite of quite extensive studying of the effects of these lanthanides
      on biota, some contradictions remain in the results. Also little is known about
      the effect of lanthanum and cerium on plant cells and their mitotic cycle,
      especially in soils. In this study, the effects of La and Ce in solutions and
      soil samples on root growth, mitotic index (MI) and frequency of aberrant cells
      (FAC) were assayed using one of the most convenient objects for testing of
      cytotoxicity - onion Allium cepa L. Bulbs were germinated on media containing La
      and Ce in concentrations 0-200 mg/l and 0-50 mg/l respectively for solutions and
      0-200 mg/kg for soil samples. After 5 days of germination in solutions, a
      significant decrease in root elongation and MI in apical meristem cells are
      shown. We have also observed an increase in the number of cells with aberrations
      at 50 mg/l La and Ce concentration. The number of observed stickiness and
      disturbed metaphase has increased significantly. Soil samples turned out to be
      less toxic compared to the solutions probably due to the decreased availability
      of REEs. In spite of this, significant cytotoxicity of soil samples containing
      the highest concentration of La and Ce (200 mg/kg) is observed. The latter may
      indicate the importance of considering the cytotoxicity of soils containing high
      lanthanides concentrations - in extraction and production areas and actively
      fertilized fields.

PMID- 30292973
TI  - Lipid accumulation responses in the liver of Rana nigromaculata induced by
      perfluorooctanoic acid (PFOA).
AB  - Perfluorooctanoic acid (PFOA) is a perfluorinated compound that is widely
      distributed, is persistent in the environment, and has a low-level chronic
      exposure effect on human health. The aim of this study was to investigate the
      peroxisome proliferator activated receptors gamma (PPARgamma) and the sterol
      regulatory element-binding protein 2 (SREBP2) signaling pathways in regulating
      the lipid damage response to PFOA in the livers of amphibians. Male and female
      frogs (Rana nigromaculata) were exposed to 0, 0.01, 0.1, 0.5 and 1 mg/L PFOA.
      After treatment, we evaluated the pathological changes in the liver by Oil Red O,
      staining and examined the total cholesterol (T-CHO) and triglyceride (TG)
      contents. The mRNA expression levels of PPARgamma, Fatty acid synthase (FAS),
      Acetyl-CoA carboxylase (ACC), Glycerol-3-phosphate acyltransferase (GPAT), SREBP2
      and 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) were measured by quantitative real
      time polymerase chain reaction (qRT-PCR). The administration of PFOA caused
      marked lipid accumulation damage in the amphibian livers. The T-CHO contents were
      elevated significantly after PFOA treatment; these results show a dose-dependent
      manner in both sexes. The TG content showed a significant increase in male
      livers, while it was elevated significantly in female livers. The RT-PCR results
      showed that the mRNA expression levels of PPARgamma, ACC, FAS, GPAT, SREBP2 and
      HMG-CoA were significantly dose-dependently increased in the PFOA-treated groups
      compared with those of the control group. Our results demonstrated that PFOA
      induced lipid accumulation also affected the expression levels of genes FAS, ACC,
      GPAT and HMG-CoA in the PPARgamma and SREBP2 signaling pathways in the liver.
      These finding will provide a scientific theoretical basis for the protection of
      Rana nigromaculata against PFOA effects.

PMID- 30292974
TI  - Response of Pseudomonas fluorescens to dimethyl phthalate.
AB  - Dimethyl phthalate (DMP) is a ubiquitous pollutant that is very harmful to
      organisms due to its mutagenicity, teratogenicity and carcinogenicity.
      Pseudomonas fluorescens (P. fluorescens) is one of the most important bacteria in
      the environment. In this study, the response of P. fluorescens to DMP was
      investigated. It was found that DMP greatly inhibited the growth and glucose
      utilization of P. fluorescens when the concentration of DMP was ranged from 20 to
      40 mg/l. The surface hydrophobicity and membrane permeability of P. fluorescens
      were also increased by DMP. DMP could lead to the deformations of cell membrane
      and the mis-opening of membrane channels. RNA-Seq and RT-qPCR results showed that
      the expression of some genes in P. fluorescens were altered, including the genes
      involved in energy metabolism, ATP-binding cassette (ABC) transporting and two
      component systems. Additionally, the productions of lactic acid and pyruvic acid
      were reduced and the activity of hexokinase was inhibited in P. fluorescens by
      DMP. Clearly, the results suggested that DMP contamination could alter the
      biological function of P. fluorescens in the environment.

PMID- 30292975
TI  - Bacterial community variations in paddy soils induced by application of
      veterinary antibiotics in plant-soil systems.
AB  - Soil bacterial communities have complex regulatory networks, which are mainly
      associated with soil fertility and ecological functions, and are likely to be
      disturbed due to antibiotics applications. The impact of antibiotics,
      particularly in mixtures form, on bacterial communities in different paddy soils
      is poorly understood. Using pyrosequencing techniques of 16 S rRNA genes, this
      study investigated the synergistic effects of veterinary antibiotics
      (sulfadiazine, sulfamethoxazole, trimethoprim, florfenicol, and clarithromycin)
      on bacterial communities in a soil-bacteria-plant system. Rice was grown under
      controlled greenhouse conditions where unplanted and planted treatments were
      doped with 200 ug kg-1 of combined antibiotics over a period of 3 months.
      Bacterial richness remained unaltered, while a significant decline was observed
      in bacterial diversity due to antibiotics in the four paddy soils. Bacteroidetes
      and Acidobacteria were increased, while Actinobacteria and Firmicutes decreased
      under antibiotics exposure. Despite antibiotics perturbation, compositional
      variations were mainly attributed to the different paddy soils which harbor
      distinct bacterial communities. Haliangium and Gaiella were among the sensitive
      genera that were negatively correlated to antibiotics perturbation. Additionally,
      electrical conductivity, total organic carbon, and total nitrogen of soil
      solution were the key physiochemical indices which significantly influenced the
      structure of bacterial communities in the paddy soils. These findings expanded
      our knowledge of effects from synergistic antibiotics application and variations
      in bacterial communities among different paddy soils.

PMID- 30292976
TI  - Reliable model established depending on soil properties to assess arsenic uptake
      by Brassica chinensis.
AB  - Generally, prediction of arsenic (As) bioavailability, mobility and its transfer
      from soil to plant is very important with respect to management of environment
      and food safety. In this study, pakchoi (Brassica chinensis) was sown in a
      greenhouse to evaluate the As transfer characteristics from different soils to
      plant system, and to investigate the possible prediction equations and key
      factors involved in As bioavailability. The results showed that As uptake of
      plant and soil As concentration was significantly and positively correlated (R2 =
      0.778; P < 0.01). A log-transformed data provided a better correlation (R2 =
      0.901; P < 0.01). Results obtained from stepwise multiple linear regression
      (SMLR) showed that soil pH and total As were important variables involved in the
      contribution of As transfer to plant. The As accumulation in plant exhibited a
      positive correlation with soil As content and pH. Various prediction equations
      were obtained from different As sources, whereas the most favourable equation was
      screened by root mean square error (RMSE) between the measured and predicted Log
      [plant As] content. The prediction model (Log [plant As] =1.34 Log [soil As]
      +0.18pH-1.25) showed the greatest accuracy of R2 = 0.978 and RMSE = 0.11, by
      combining the data of three As treatments (45 observed data points). These
      current findings are quite useful and could be used for predicting the As
      transfer from soil to plant system.

PMID- 30292977
TI  - Neuropsychological assessment of patients undergoing surgery due to low-grade
      glioma involving the supplementary motor area.
AB  - OBJECTIVE: The aim of the study was to establish the usefulness of various
      neuropsychological tests in patients undergoing surgery due to low-grade glioma
      (LGG) involving supplementary motor area (SMA). PATIENTS AND METHODS: 21 patients
      diagnosed with LGG involving the SMA underwent, before and after surgery,
      screening tests (Mini Mental State Examination - MMSE, Montreal Cognitive
      Assessment - MoCA and Frontal Assessment Battery - FAB), tests to assess language
      functions (Addenbrook's Cognitive Examination-III - ACE-III, phonetic fluency
      tests and semantic fluency tests), tests to assess memory functions (Rey's 15
      word test - RAVLT and Diagnostic Test for Brain Damage by Hillers- DCS), tests to
      assess executive functions (Wisconsin Card Sorting Test - WCST, Ruff Figural
      Fluency Test - RFFT and Trail Making Test). RESULTS: Before surgery, in the
      screening tests the patients obtained below normal scores in the MoCA test only.
      After surgery, the scores of such tests were significantly worse than the scores
      before surgery, while the MMSE test scores continued to be within the normal
      range. In phonetic and semantic fluency tests, the patients obtained worse
      scores, both before and after surgery. The differences in the test scores between
      the two periods, i.e. before and after surgery, were statistically significant.
      Although the patients obtained worse scores both before and after surgery in the
      ACE III test, the differences in the test scores were not statistically
      significant. The scores obtained in all tests assessing the executive and memory
      functions before and after surgery were within the normal range. The scores in
      such tests (except the WCCT) dropped significantly after surgery. CONCLUSIONS:
      Patients diagnosed with LGG involving the SMA reveal the impairment of cognitive
      functions, in particular language functions. After surgery, a significant
      impairment of all elementary cognitive functions, such as attention, memory,
      language and executive functions and complex cognitive functions, occurs. The
      most sensitive tests to detect cognitive disorders, executive dysfunctions and
      speech disturbances in patients undergoing surgery due to glioma include the
      MoCA, FAB and Phonetic and Semantic Fluency Tests.

PMID- 30292978
TI  - Diffuse low grade glioma after the 2016 WHO update, seizure characteristics,
      imaging correlates and outcomes.
AB  - OBJECTIVES: The majority of patients with supratentorial diffuse grade II glioma
      present with seizures, which adversely affect quality of life. The exact
      mechanism of epileptogenesis is unknown and the influence of tumour
      characteristics, radiological and histological, are not well studied,
      particularly following the introduction of molecular genetics in the 2016 WHO
      reclassification of gliomas. We sought to define predictors of seizure
      development and outcome in low grade glioma. PATIENTS AND METHODS: A
      retrospective review of patients who underwent resection of a supratentorial
      grade II glioma in a single institution. All patients underwent surgery at
      initial presentation with the aim of maximal safe resection. Presenting symptoms
      and radiological variables were recorded, including eloquent location, cortical
      involvement, tumour margins and tumour volume. Extent of resection (EOR), surgery
      type (awake vs asleep) and seizure outcome were analysed. Using molecular
      genetics data the original histology was reclassified according to the 2016 WHO
      update. RESULTS: 63 patients were included, 45 (71%) presented with seizures. 36
      (57%) had oligodendroglioma and 27 astrocytoma. IDH-1 mutation was present in 53
      (84%). 18 (29%) had tumour in an eloquent location. 33 (73%) were Engel class I
      following surgery at median follow up of 43 months. 6 patients were Engel II, 6
      class III. Complete and near total resection were associated with improved Engel
      class compared to subtotal resection. No factors such as age, tumour location,
      tumour margins or tumour molecular genetics (including IDH-1 mutation) predicted
      better seizure outcome. Updated histological subtype did not predict the presence
      of seizures at initial diagnosis, only tumour heterogeneousity on initial MRI (p
      = 0.043). More patients who underwent awake craniotomy with intraoperative
      mapping were Engel class 1 post-operatively than those operated under general
      anaesthetic (84% vs 65%). Tumour volume at presentation did not correlate with
      seizure outcome but impacts on the EOR. CONCLUSION: Seizure outcome is directly
      related to EOR in low grade glioma, which can be predicted by the initial tumour
      volume. Tumour histological subtype, including updated molecular genetic
      classification did not predict seizure development or outcome in this series. The
      use of awake craniotomy results in greater EOR and improved Engel Class following
      surgery.

PMID- 30292979
TI  - Prognostic and predictive biomarkers for somatostatin analogs, peptide receptor
      radionuclide therapy and serotonin pathway targets in neuroendocrine tumours.
AB  - Neuroendocrine tumours (NETs) are a heterogeneous group of neoplasms regarding
      their molecular biology, clinical behaviour, prognosis and response to therapy.
      Several attempts to establish robust predictive biomarkers have failed. Neither
      tissue markers nor blood borne ones have proven to be successful yet. Circulating
      tumour cells (CTCs) as "liquid biopsies" could provide prognostic information at
      the time a therapeutic decision needs to be made and could be an attractive tool
      for tumour monitoring throughout the treatment period. However, "liquid biopsies"
      are far from becoming the standard biomarker in NETs. Promising results have been
      presented over the last few years using a novel biomarker candidate, a
      multianalyte algorithm analysis PCR-based test (NETest). New technologies will
      open the field to different ways of approaching the biomarker conundrum in NETs.
      However, the complications derived from being a heterogeneous group of
      malignancies will remain with us forever. In summary, there is an unmet need to
      incorporate new biomarker candidates into clinical research trials to obtain a
      robust prospective validation under the most demanding scenario.

PMID- 30292980
TI  - Transcriptomic view of survival during early seedling growth of the extremophyte
      Haloxylon ammodendron.
AB  - Seedling establishment in an extreme environment requires an integrated genomic
      and physiological response to survive multiple abiotic stresses. The
      extremophyte, Haloxylon ammodendron is a pioneer species capable of colonizing
      temperate desert sand dunes. We investigated the induced and basal transcriptomes
      in H. ammodendron under water-deficit stress during early seedling establishment.
      We find that not only drought-responsive genes, but multiple genes in pathways
      associated with salt, osmotic, cold, UV, and high-light stresses were induced,
      suggesting an altered regulatory stress response system. Additionally, H.
      ammodendron exhibited enhanced biotic stress tolerance by down-regulation of
      genes that were generally up-regulated during pathogen entry in susceptible
      plants. By comparing the H. ammodendron basal transcriptome to six closely
      related transcriptomes in Amaranthaceae, we detected enriched basal level
      transcripts in H. ammodendron that shows preadaptation to abiotic stress and
      pathogens. We found transcripts that were generally maintained at low levels and
      some induced only under abiotic stress in the stress-sensitive model, Arabidopsis
      thaliana to be highly expressed under basal conditions in the Amaranthaceae
      transcriptomes including H. ammodendron. H. ammodendron shows coordinated
      expression of genes that regulate stress tolerance and seedling development
      resource allocation to support survival against multiple stresses in a sand dune
      dominated temperate desert environment.

PMID- 30292981
TI  - Trans-aconitic acid inhibits the growth and photosynthesis of Glycine max.
AB  - Grasses producing trans-aconitic acid, a geometric isomer of cis-aconitic acid,
      are often used in Glycine max rotation systems. However, the effects of trans
      aconitic acid on Glycine max are unknown. We conducted a hydroponic experiment to
      evaluate the effects of 2.5-10 mM trans-aconitic acid on Glycine max growth and
      photosynthesis. The results revealed that the enhanced H2O2 production in the
      roots increased the membrane permeability and reduced the water uptake. These
      effects culminated with a reduced stomatal conductance (gs), which seems to be
      the main cause for a decreased photosynthetic rate (A). Due to low gs, the
      limited CO2 assimilation may have overexcited the photosystems, as indicated by
      the high production of H2O2 in leaves. After 96 h of incubation, and due to H2O2
      induced damage to photosystems, a probable non-stomatal limitation for
      photosynthesis contributed to reducing A. This is corroborated by the significant
      decrease in the quantum yield of electron flow through photosystem II in vivo
      (PhiPSII) and the chlorophyll content. Taken together, the damage to the root
      system and photosynthetic apparatus caused by trans-aconitic acid significantly
      reduced the Glycine max plant growth.

PMID- 30292982
TI  - Recurrent water deficit causes alterations in the profile of redox proteins in
      citrus plants.
AB  - Plant acclimation to recurrent stress involves profound alterations in multiple
      genetic, metabolic and physiological processes. Stressful conditions usually
      implicate imbalance in reactive oxygen species (ROS) production and removal
      rates, which may lead to oxidative stress. However, the primary cellular targets
      of oxidative stress and their relevance in plant acclimation to abiotic stresses
      remains poorly characterized. By comparing redox proteomic and sugar profiles in
      citrus Valencia (VO) scions grafted onto two rootstocks with different soil water
      extraction capacities - Rangpur Lime (RL) and Sunki Maravilha (SM) - here we
      demonstrate that both ROS-mediated post-translational protein modification and
      changes in sugar composition are associated with acclimation to recurrent drought
      in citrus. The redox proteomic analysis of the distinct scion/rootstock
      combinations exposed to one (WD1), two (WD2) or three (WD3) water deficit
      episodes revealed a total of 32 and 55 redox protein spots present in VO/RL and
      VO/SM plants, respectively. Mass spectrometry analysis of these protein spots
      revealed essential targets of ROS-mediated posttranslational protein modification
      in citrus plants challenged by recurrent drought. The oxidation of cysteine thiol
      groups into glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was shown to
      increase in WD3 samples of the VO/RL combination, whereas the opposite was
      observed for the VO/SM combination. Similarly, recurrent drought promoted the
      oxidation of catalase thiol groups in VO/SM, but not in VO/RL. Carbohydrate
      profiling revealed that glucose, fructose and galactose may also contribute to
      the phenotypic differences observed between the citrus genotypes exposed to
      drought. These findings reveal for the first time that recurrent drought
      differentially affects the profile of redox proteomics of citrus, suggesting that
      this alteration may be part of the stress memory in perennial plants.

PMID- 30292984
TI  - Metabolomic study of serum, urine and bronchoalveolar lavage fluid based on gas
      chromatography mass spectrometry to delve into the pathology of lung cancer.
AB  - This study explores for the first time the combination of serum, urine and
      bronchoalveolar lavage fluid (BALF) to deep insight into the pathology of lung
      cancer (LC) using a metabolomic platform based on gas chromatography mass
      spectrometry (GCMS). The study includes LC patients, healthy control group (HC)
      and a group of patients with noncancerous lung diseases (NCC) used as a control
      group respect to BALF because of the invasive nature this fluid collection. The
      metabolomic platform was applied to serum, urine and BALF samples in order to
      compare the metabolomic profiles of these biological fluids and establish
      metabolic similarities and differences between them. The application of PLS-DA
      presented a clear classification of groups for all types of samples, indicating
      the existence of altered metabolites in LC. Twenty six and thirty one perturbed
      metabolites in the LC were annotated in the comparison of serum and urine
      samples. On the other hand, sixteen metabolites were altered in BALF of LC
      patients compared to NCC. The pathway analysis indicated that several amino acid
      metabolic routes were the most affected in LC. Finally, ROC curves were applied
      to the dataset and metabolites with an AUC value higher than 0.75 were considered
      as relevant in the progression of LC.

PMID- 30292983
TI  - Isotope dilution LC-ESI-MS/MS and low resolution selected reaction monitoring as
      a tool for the accurate quantification of urinary testosterone.
AB  - A new analytical method for the quantification of testosterone in human urine
      samples by isotope dilution mass spectrometry is proposed. A standard solution of
      13C2-testosterone is added to the samples at the beginning of the sample
      preparation procedure and then the measurements are carried out by UHPLC-ESI
      MS/MS. In the proposed method, the resolution of the first quadrupole of the
      tandem MS instrument is reduced to transmit the whole precursor ion cluster to
      the collision cell and measure the isotopic distribution of the in-cell product
      ions with a small number of SRM transitions. The construction of a methodological
      calibration graph is avoided using a labelled analogue previously characterised
      in terms of concentration and isotopic enrichment in combination with multiple
      linear regression. In this way, the molar fractions of natural and labelled
      testosterone are calculated in each sample injection and the amount of endogenous
      testosterone computed from the known amount of labelled analogue. Recovery values
      between 97 and 107% and precisions between 0.4 and 3.7% (as %RSD) were obtained
      for testosterone concentrations in urine in the range of 1 to 8 ng g-1. The
      proposed low resolution SRM methodology was compared for the analysis of human
      urine samples with the traditional IDMS method based on a calibration graph and
      the IDMS method based on multiple linear regression combined with standard
      resolution SRM. A similar accuracy and precision was obtained by the three tested
      approaches. However, using the low resolution SRM method there was no need to
      resort to calibration graphs or to specific dedicated software to calculate
      isotopic distributions by tandem MS and a higher sensitivity was obtained. The
      proposed low resolution SRM method was successfully applied to the analysis of
      the certified freeze-dried human urine NMIA MX005.

PMID- 30292985
TI  - Two findings of gallstones in archaeological mummies from Colombia.
AB  - Results involving the analysis of gallstones found in two pre-Hispanic Colombian
      mummies are presented. By applying SEM, X-ray diffraction (XRD), sectioning, and
      CT-scan Hounsfield Units, we were able to identify these choleliths as mainly
      formed by cholesterol. The number of reports on gallstones in archaeological
      human remains from South America is very small, making these two cases an
      important addition to what little is known about ancient gallstone disease on the
      continent.

PMID- 30292986
TI  - "Aged" autopsy gallstones simulating dry bone context: A morphological,
      histological and SEM-EDS analysis.
AB  - OBJECTIVE: The aim of this paper is to provide information on the morphology and
      composition of gallstones based on clinical samples in order to assist
      paleopathologists and bioarchaeologists in recognizing their presence in
      archaeological contexts. MATERIALS AND METHODS: 270 gallstones were extracted and
      macerated from autopsies conducted at the Istituto di Medicina Legale in Milan
      (Italy) in order to simulate a dry bone recovered from archaeological contexts.
      Morphological, histological, and elemental variation was documented. RESULTS:
      Gallstones vary in size, shape, color and texture. The cross-sectional surface
      correlates with chemical composition and is a valuable tool for classification
      into subcategories of stones. Histological analysis can confirm the
      classification. Elemental analysis yielded a higher frequency of carbon, calcium
      and phosphorus. CONCLUSIONS: Although identification of gallstones in
      archaeological contexts can be challenging, familiarity with morphological,
      histological, and elemental variation can assist researchers in the field and
      laboratory. SIGNIFICANCE: Identifying gallstones in archaeological populations
      will assist researchers in estimating their frequency in the past and the
      environmental, cultural, and biological conditions leading to their presence.
      LIMITATIONS: Small sample size derived from a modern and limited autopsy
      population may minimize the types and degree of variation present in the past.
      Effects of climate, soil, and taphonomy were not evaluated. SUGGESTIONS FOR
      FURTHER RESEARCH: Examination of larger samples derived from diverse populations
      may reveal greater variation or more diagnostic aspects of stones.

PMID- 30292987
TI  - Preliminary evidence of an association between increased cortical inhibition and
      reduced suicidal ideation in adolescents treated for major depression.
AB  - BACKGROUND: Suicide is a leading cause of death among youth. Prior research using
      transcranial magnetic stimulation (TMS) has implicated deficits in GABAergic
      cortical inhibition in adolescent suicidal behavior, yet no studies have assessed
      whether cortical inhibition varies over time in conjunction with changes in
      suicidal ideation (SI). This study examined dynamic changes in long-interval
      intracortical inhibition (LICI), a TMS measure of GABAB-mediated inhibition, and
      their relationship with changes in SI in a small sample of adolescents undergoing
      pharmacologic treatment for depression. METHODS: Ten depressed adolescents (aged
      13-17) underwent clinical assessment and TMS testing at baseline and again at
      follow-up. All were treated with antidepressant medication in the interim. SI was
      measured with the Columbia Suicide Severity Rating Scale (C-SSRS) Intensity of
      Ideation subscale. LICI was measured at interstimulus intervals of 100 and 150
      ms. RESULTS: There was a significant partial correlation, controlling for change
      in depression severity, between DeltaLICI-100 and change in SI as measured by
      DeltaC-SSRS (rho = .746, df = 7, p = .021), which remained after also controlling
      for time to follow-up assessment (rho = .752, df = 6, p = .032). No significant
      correlation was observed between DeltaLICI-150 and change in SI. LIMITATIONS:
      Sample size; variable follow-up interval; inability to control for age, sex, and
      potential treatment effects. CONCLUSIONS: These data offer preliminary signal of
      an association between increases in GABAB-mediated cortical inhibition and
      reduction in SI over time in adolescents treated for depression. Further studies
      are warranted to explore the role of cortical inhibition in adolescent suicidal
      ideation and behavior.

PMID- 30292988
TI  - The effect of cancer on the labor supply of employed men over the age of 65.
AB  - This paper investigates the relationship between cancer diagnosis and the labor
      supply of employed men over the age of 65. While almost 60% of male cancers are
      diagnosed in men over the age of 65, no previous research has examined the effect
      that cancer has on this age group, which is surprising given the relevance of
      this group to public policy. With data from the Health and Retirement Study, I
      show that cancer has a significant negative effect on the labor supply of these
      workers. Using a combination of linear regression models and propensity score
      matching, I find that respondents who are diagnosed with cancer work 3 fewer
      hours per week than their non-cancer counterparts. They are also 10 percentage
      points more likely to stop working. This reduction seems to be driven by a
      deterioration in physical and mental health.

PMID- 30292989
TI  - Environmental monitoring and risk assessment of pesticide residues in surface
      waters of the Louros River (N.W. Greece).
AB  - Estuarine environments are being constantly stressed by new sources of pollution
      (e.g. pesticides) derived from activities of industry and intensive agriculture.
      The present study aims at quantify pesticides of three different categories
      (fungicides, herbicides and insecticides) in the Louros River (Epirus region,
      North-Western Greece). A monitoring study of 34 compounds was carried out in
      surface river waters from June 2011 until May 2012. Seven water sampling stations
      were established and 35 water samples were collected. A solid-phase extraction
      (SPE) method coupled with gas chromatography-mass spectrometry (GC-MS) and liquid
      chromatography-mass spectrometry (LC-MS), depending on the compound, was
      developed and validated. During the monitoring study 25 pesticides were detected
      (13 herbicides, 9 insecticides, 3 fungicides). The most commonly encountered
      pesticides were quizalofop-ethyl, trifluralin and pendimethaline. Tebufenpyrad
      was found in all sampling stations and seasons, with the highest concentrations
      of 0.330 MUg/L at Tsopeli Lagoon exceeding the rather low concentrations reported
      nationwide. Regarding the environmental risk due to the presence of target
      compounds in surface waters, this was estimated by calculating risk quotients
      (RQs) for different aquatic organisms (algae, zooplankton and fish). The results
      denoted a possible threat for the aquatic environment, rendering in this way the
      RQ method as a useful screening tool. In any case, further extensive study is
      needed for acetochlor, pirimiphos-methyl, endosulfan-a and azinphos-ethyl in
      order to better correlate their occurrence and potential toxic effects in aquatic
      life and humans.

PMID- 30292990
TI  - Ecological and socioeconomic effects of ecological restoration in China's Three
      Rivers Source Region.
AB  - The Three Rivers Source Region, in the central Qinghai-Tibet Plateau, has a
      sensitive and fragile ecological environment. Adverse changes in climate and
      human activities have degraded the grassland ecosystems. To mitigate or reverse
      the degradation, alleviate rural poverty, and stimulate economic development,
      ecological restoration projects have been implemented. In the present study, our
      goal was to assess the ecological and socioeconomic effects of these programs
      based on land-use change, grassland NPP, and household surveys. Household data
      were collected using structured questionnaires in 11 villages from three
      counties, with average elevation above 3773 m asl. We found that the grassland
      degradation had been mitigated, especially after the implementation of ecological
      restoration programs since 2005 in a regional nature reserve in Qinghai Province.
      Household income depends strongly on the region's natural resources, so the
      grassland ecosystems are still at risk of unsustainable use. A household that
      understood the effects of the ecological restoration programs and had received
      training to participate in the programs was more willing to participate in future
      programs. Our findings suggest that for successful restoration, it is essential
      to help residents of the study area thoroughly understand the ecological
      restoration programs and learn the restoration techniques before implementation
      of such programs. This is because the participation of the residents depended
      strongly on both their income and their satisfaction with the ecological
      restoration programs.

PMID- 30292991
TI  - Soil microbial community structure in the rhizosphere of Robinia pseudoacacia L.
      seedlings exposed to elevated air temperature and cadmium-contaminated soils for
      4 years.
AB  - The co-occurrence of heavy metal contamination of soils and increasing air
      temperature can affect the microbial community in rhizosphere soils by altering
      the allocation of plant photosynthates to roots. Here, we investigated the
      community structure of bacteria, fungi, ammonia oxidizing bacteria (AOB) and
      ammonia oxidizing archaea (AOA) in the rhizosphere of Robinia pseudoacacia L.
      seedlings exposed to elevated air temperature (+1.99  degrees C) and cadmium (Cd)
      for 4 years. Elevated temperature increased the richness of bacterial and AOA
      communities by 15.1% to 43.8% and by 1.4% to 18.6%, respectively, and decreased
      fungal and AOB richness by 3.7% to 28.7% and by 2.1% to 30.6%, respectively,
      under Cd exposure. Elevated temperature combined with Cd exposure decreased
      fungal diversity by 1.5% to 14.0%. However, elevated temperature decreased the
      diversity of bacteria, AOB and AOA by 1.4%, 17.4% and 10.1%, respectively, under
      1.0 mg Cd kg-1 dry soil and increased the diversity of these taxa by 1.5%, 15.3%
      and 9.2%, respectively, under 5.0 mg Cd kg-1 dry soil relative to Cd exposure
      alone. Elevated temperature led to increased abundance of genera such as
      Methylobacterium, Stenotrophomonas, and Archangium and decreased abundance of
      genera including Ramlibacter, Microascus and Nitrosospira under Cd exposure. Over
      all, 4 years of exposure to elevated temperature had a greater effect on the
      community structure of bacteria, fungi, AOB and AOA when combined with Cd
      pollution.

PMID- 30292992
TI  - Marine vegetation analysis for the determination of volatile methylsiloxanes in
      coastal areas.
AB  - Volatile methylsiloxanes (VMSs) are massively produced chemicals that comprise a
      wide range of industrial and household applications. The presence of cyclic and
      linear VMSs in several environmental matrices and ecosystems indicates
      persistence associated with a potential of (bio)accumulation and food web
      transfer with possible toxicological effects. Due to the high anthropogenic
      pressure in its vicinities particularly in summer, coastal areas in Southern
      European countries are potential hotspots for the presence of VMSs. The massive
      afflux of tourists and consequent increase of the use of personal care products
      (PCPs) with VMSs in their formulations highlight the importance of VMSs
      assessment in such areas. In this study, different species of marine vegetation
      (algae and seaweed) were collected in three different geographical areas,
      covering the Atlantic Ocean (North coast of Portugal), as well as the
      Mediterranean Sea (coasts of the Region of Murcia, Spain and of the city of
      Marseille, France). Samples were analysed for the determination of 4 cyclic (D3,
      D4, D5, D6) and 3 linear (L3, L4, L5) VMSs employing a QuEChERS extraction
      methodology, followed by gas chromatography/mass spectrometry (GC/MS)
      quantification. VMSs were detected in 92% of the 74 samples analysed, with the
      sum of the concentrations per sample ranging from below the limit of detection
      (LOD) to 458 +/- 26 ng.g-1dw (dry weight). A strong predominance of cyclic VMSs
      over linear ones was verified in almost all samples studied, with D5 and D6 found
      at higher concentrations. Seasonal variation was also assessed and despite higher
      levels of VMSs being identified mostly in summer months, clear seasonal trends
      were not perceived. It was also noted that generally the higher incidence of VMSs
      occurred in samples from urban and industrialized areas or in the vicinities of
      WWTPs, suggesting a direct input from these sources in the levels of siloxanes
      observed.

PMID- 30292993
TI  - Dynamic monitoring of aeolian desertification based on multiple indicators in
      Horqin Sandy Land, China.
AB  - Aeolian desertification has become one of the most serious environmental and
      socioeconomic problems facing the world today. Quantitative remote sensing
      technology is an important means to achieve the development trends of aeolian
      desertified land (ADL). To compensate for the shortcomings in the time scale of
      Landsat Thematic Mapper and other high-spatial-resolution remote sensing data,
      this study introduces Moderate Resolution Imaging Spectroradiometer time series
      data and products to invert the monitoring indicators of ADL. The QUEST (quick,
      unbiased, and efficient statistical tree) classification method was used to
      establish the extraction model of ADL based on multiple indicators. The ADL time
      series dataset was extracted from 2000 to 2015, and the characteristics of ADL
      and its spatial-temporal dynamics were analyzed. These results were combined with
      meteorological data and socioeconomic statistics to discuss the main factors
      influencing ADL. The results showed that, by the end of 2015, the total area of
      ADL was 32,633 km2, accounting for 26.02% of the study area. The slight,
      moderate, severe, and extremely severe ADL accounted for 51.39%, 34.11%, 10.31%,
      and 4.20%, respectively. The total area of ADL decreased significantly at a rate
      of 2388.60 km2 y-1 from 2000 to 2015. The decreasing area was dominated by the
      slight and moderate ADL. The reversal of ADL exhibited significant correlations
      with an increase of annual precipitation and a decrease of annual maximum wind
      velocity (p < 0.01). The impact of annual maximum wind velocity on ADL is more
      important than annual precipitation. Increases in population density and the
      number of livestock did not promote the development of ADL. A series of
      ecological protection projects and policies created advantageous conditions for
      the reversal of ADL. This research provides a new method for monitoring ADL and
      useful information for controlling and managing aeolian desertification in this
      region.

PMID- 30292994
TI  - Pollution and children's health.
AB  - FINDINGS: The Lancet Commission on Pollution and Health found that pollution -
      air, water, soil, and chemical pollution - was responsible in 2016 for 940,000
      deaths in children worldwide, two-thirds of them in children under the age of 5.
      Pollution is inequitably distributed, and the overwhelming majority of pollution
      related deaths in children occurred in low- and middle-income countries (LMICs).
      Most were due to respiratory and gastrointestinal diseases caused by polluted air
      and water. Pollution is linked also to multiple non-communicable diseases (NCDs)
      in children including low birth weight, asthma, cancer and neurodevelopmental
      disorders, and these diseases are on the rise. The full impact of pollution,
      especially chemical pollution on the global burden of pediatric disease is not
      yet known, but almost certainly is undercounted because patterns of chemical
      exposure are not well charted and the potential toxicity of many chemical
      pollutants has not been characterized. The list of pediatric NCDs attributed to
      pollution will likely expand as the health effects of newer chemical pollutants
      are better defined and additional associations between pollution and disease are
      discovered. CONCLUSION: Pollution prevention presents a major, largely
      unexploited opportunity to improve children's health and prevent NCDs, especially
      in LMICs. Failure to incorporate pollution prevention into NCD control programs
      is a major missed opportunity for disease prevention.

PMID- 30292995
TI  - Distinct community structure and microbial functions of biofilms colonizing
      microplastics.
AB  - Microplastics are frequently detected in freshwater environments, serving as a
      new factitious substrate for colonization of biofilm-forming microorganisms.
      Distinct microbial assemblages between microplastics and surrounding waters have
      been well documented; however, there is insufficient knowledge regarding biofilm
      colonization of plastic and non-plastic substrates, despite the fact that
      microbial communities generally aggregate on natural solid surfaces. In this
      study, the effects of substrate type on microbial communities were evaluated by
      incubation of biofilms on microplastic substrates (polyethylene and
      polypropylene) and natural substrates (cobblestone and wood) for 21 days under
      controlled conditions. Results from high-throughput sequencing of 16S rRNA
      revealed that the alpha diversity (richness, evenness, and diversity) was lower
      in the microplastic-associated communities than in those on the natural
      substrates, indicating substrate-type-coupled species sorting. Distinct community
      structure and biofilm composition were observed between these two substrate
      types. Significantly higher abundances of Pirellulaceae, Phycisphaerales,
      Cyclobacteriaceae, and Roseococcus were observed on the microplastic substrates
      compared with the natural substrates. Simultaneously, the functional profiles
      (KEGG) predicted by Tax4Fun showed that the pathways of amino acid metabolism and
      metabolism of cofactors and vitamins were increased in biofilms on the
      microplastic substrates. The findings illustrate that microplastic acts as a
      distinct microbial habitat (compared with natural substrates) that could not only
      change the community structure but also affect microbial functions, potentially
      impacting the ecological functions of microbial communities in aquatic
      ecosystems.

PMID- 30292996
TI  - Effects of the exposure to ultrafine particles on heart rate in a healthy
      population.
AB  - The correlation amongst exposure to ultrafine particle concentrations and heart
      rate in a large healthy population was investigated. The study was conducted by
      continuously monitoring for seven days fifty volunteers in terms of exposure to
      particle concentrations, heart rate and physical activity performed through
      portable monitors. Data were analyzed adopting a linear mixed model able to
      manage the obtained repeated measures and to recognize a general trend resulting
      from the subject-specific patterns. Results show that the short-term exposure to
      ultrafine particle concentrations is positively associated with the heart rate
      for the different physical activities of the subject investigated (laying down,
      sitting, standing positions). In particular, a logarithmic correlation was
      recognized with a sharper increase of about 4-6 bpm for a variation of the
      particle number concentration of 2 * 104 part/cm3 and a slighter effect for
      further increases of about 0.1-0.2 * 10-4 bpm/(part/cm). CAPSULE: A positive
      correlation can be associated between the exposure to ultrafine particles and the
      heart rate.

PMID- 30292997
TI  - Comparison of sustainable biosorbents and ion-exchange resins to remove Sr2+ from
      simulant nuclear wastewater: Batch, dynamic and mechanism studies.
AB  - Removal of Sr2+ from aqueous media presents particular challenges, especially in
      complex wastes such as nuclear industry liquors. Commercial sorbents while
      effective, can be highly expensive and subject to negative effects from competing
      ions. Here we evaluate two potential biosorbents (crab carapace and spent
      distillery grain) as potential alternatives and compare their performance to two
      commercial sorbents for Sr2+ removal at industrially relevant concentrations (low
      mg/L). Physical and structural characterization of the materials was undertaken,
      and batch and dynamic studies were performed on Sr2+ solutions and simulated
      nuclear wastewater. Sorption performance was quantified with respect to contact
      time, initial concentration and ion-competition. Removal efficiencies were 20-70%
      for the biosorbents compared to 55-95% for the commercial materials. Results
      indicated sorption was predominantly through monolayer coverage on homogenous
      sites and could be described using a pseudo-second-order kinetic model. Studies
      with the simulant liquor showed Sr2+ sorption was reduced by 10-40% due to ion
      competition for sites. Characterization of biosorbents before and after Sr2+
      sorption suggested that outer-sphere complexation and ion-exchange were the
      primary Sr2+ removal mechanisms. The efficiency of crab carapace for Sr2+ removal
      from aqueous media (with adsorption capacity 3.92 mg/g.) at industrially relevant
      concentrations, together with its mechanical stability, implementation and
      disposal cost, makes it a competitive option compared to other biosorbents and
      commercial materials reported in the literature.

PMID- 30292998
TI  - Testing the performance of one and two box models as tools for risk assessment of
      particle exposure during packing of inorganic fertilizer.
AB  - Modelling of particle exposure is a useful tool for preliminary exposure
      assessment in workplaces with low and high exposure concentrations. However,
      actual exposure measurements are needed to assess models reliability. Worker
      exposure was monitored during packing of an inorganic granulate fertilizer at
      industrial scale using small and big bags. Particle concentrations were modelled
      with one and two box models, where the emission source was estimated with the
      fertilizer's dustiness index. The exposure levels were used to calculate inhaled
      dose rates and test accuracy of the exposure modellings. The particle number
      concentrations were measured from worker area by using a mobility and optical
      particle sizer which were used to calculate surface area and mass concentrations.
      The concentrations in the worker area during pre-activity ranged 63,797-81,073 cm
      3, 4.6 * 106 to 7.5 * 106 MUm2 cm-3, and 354 to 634 MUg m-3 (respirable mass
      fraction) and during packing 50,300 to 85,949 cm-3, 4.3 * 106 to 7.6 * 106 MUm2
      cm-3, and 279 to 668 MUg m-3 (respirable mass fraction). Thus, the packing
      process did not significantly increase the exposure levels. Chemical exposure was
      also under control based on REACH standards. The particle surface area deposition
      rate in respiratory tract was up to 7.6 * 106 MUm2 min-1 during packing, with 52%
      61% of deposition occurring in the alveolar region. Ratios of the modelled and
      measured concentrations were 0.98 +/- 0.19 and 0.84 +/- 0.12 for small and big
      bags, respectively, when using the one box model, and 0.88 +/- 0.25 and 0.82 +/-
      0.12, when using the two box model. The modelling precision improved for both
      models when outdoor particle concentrations were included. This study shows that
      exposure concentrations in a low emission industrial scenario, e.g. during
      packing of a fertilizer, can be predicted with a reasonable accuracy by using the
      concept of dustiness and mass balance models.

PMID- 30292999
TI  - Characterizing the removal routes of seven pharmaceuticals in the activated
      sludge process.
AB  - The removal routes of pharmaceuticals especially biodegradation routes in the
      activated sludge process are still unclear. Some studies indicated
      pharmaceuticals were mainly removed via nitrification process (autotrophic
      biodegradation), while others suggested pharmaceuticals were mainly removed via
      COD degradation process (heterotrophic biodegradation). These unclear problems
      limited the improvements of pharmaceuticals removal. In this study, in order to
      elucidate three biodegradation routes (nitrification, COD degradation, or both
      nitrification and COD degradation), autotrophic and heterotrophic reactors were
      individually developed to separate nitrification and COD degradation form the
      activated sludge process (mix-trophic process including nitrification and COD
      degradation). Furthermore, the pharmaceuticals removal routes of adsorption,
      hydrolysis, and oxidation were also studied. Among six degradable
      pharmaceuticals, heterotrophic biodegradation and adsorption were the major
      removal routes. Two sulfonamides of five antibiotics were predominantly removed
      by COD degradation process, while nitrification and adsorption had no
      contributions. Adsorption, hydrolysis, nitrification, and COD degradation were
      the main elimination routes of cefalexin. COD degradation and adsorption were the
      dominant removal routes of norfloxacin. Tetracycline was mainly removed by the
      adsorption route, and hydrolysis and oxidation also played a role. For two drugs,
      ibuprofen was removed mainly via nitrification and COD degradation, and no
      adsorption occurred. Diclofenac could not be removed at all and was persistent in
      the aerobic conditions. Kinetic studies showed that biodegradation of the two
      sulfonamides, cefalexin, norfloxacin, and ibuprofen followed first-order kinetics
      rather than zero-order or second-order kinetics.

PMID- 30293000
TI  - The occurrence of contaminants of emerging concern in Slovenian and Croatian
      wastewaters and receiving Sava river.
AB  - This study investigated the occurrence of 48 contaminants of emerging concern
      (CECs) in wastewater effluents from three Slovenian and three Croatian waste
      water treatment plants (WWTPs) representing the major inputs into the upper and
      middle course of the Sava River and simultaneously in the Sava River itself. Two
      sampling campaigns were carried out (May and July 2017). Samples were extracted
      using solid-phase extraction and analysed by gas chromatography - mass
      spectrometry. In effluents, 23 CECs were >LOQ with caffeine and the UV-filter 4
      hydroxybenzophenone (H-BP) present in the highest concentrations (<49,600 ng L-1
      and <28,900 ng L-1, respectively) and most frequently detected (detection
      frequency; DFr > 83.3%). Bisphenol B and E were detected for the first time in WW
      from Velika Gorica (May) and Zapresic (July), respectively. In surface water
      (SW), 19 CECs were detected >LOQ with CAF again being the most abundant and most
      frequently detected (DFr = 92.9%). Bisphenols AP, CL2, P and Z were detected >LOQ
      for the first time in European SW. Active pharmaceutical ingredients naproxen,
      ketoprofen, carbamazepine and diclofenac; the preservative methyl paraben; CAF
      and UV-filter HM-BP were the most abundant CECs in SW and WW. An increasing trend
      in the total CEC load downstream was observed, indicating the cumulative effects
      of individual sources along the river. The Croatian Zapresic, Zagreb and Velika
      Gorica WWTP effluents contributed the most towards the enhanced loads of the CECs
      studied probably due to their size or insufficient treatment. HM-BP was the only
      compound found at a levels exhibiting high environmental risk (RQ = 1.13)
      downstream from Ljubljana and Domzale-Kamnik WWTPs. Other SW samples that
      contained HM-BP, ibuprofen (API) and/or benzyl paraben (preservative) posed a
      medium risk to the environment. The results suggest the need for further
      monitoring of CECs in the Sava River Basin.

PMID- 30293001
TI  - Trace metal characterization and fluxes from the Guadiana, Tinto-Odiel and
      Guadalquivir estuaries to the Gulf of Cadiz.
AB  - Metals transported into the coastal zone by the South Iberian rivers are key to
      understand the biogeochemical cycles and distribution of trace elements in the
      Gulf of Cadiz (GoC hereinafter) and the exchange with the Mediterranean Sea.
      Previous studies carried out in the 80s have suggested that metal enrichment in
      the Alboran Sea (Western Mediterranean) is related with fluvial inputs from acid
      mine drainage from the Tinto and Odiel rivers. The present study evaluates the
      contribution of dissolved trace metal concentrations (i.e. Cd, Co, Cu, Fe, Mo,
      Ni, Pb, V, Zn) from the three main rivers discharging into the GoC (i.e.
      Guadiana, Tinto-Odiel and Guadalquivir rivers). Our results show that the metal
      composition of water discharged from each river is impacted by the activities
      developed in the course of the rivers, which clearly influence the GoC coastal
      surface waters composition. Metal fluxes from the Guadalquivir river are
      quantitatively higher than those from the Tinto-Odiel (e.g. up to 73% and 19%
      higher for Ni and Cu, respectively). Although the metal concentrations spatial
      distributions in the GoC are dominated by the circulation pattern between the
      Atlantic and the Mediterranean Sea, the concentrations within the GoC continental
      shelf could be explained by a greater contribution from the Guadalquivir estuary
      (e.g. 80.5%, 54.6%, 56.5% and 56.6% for Ni, Cu, Mo, and V respectively).

PMID- 30293002
TI  - Zero-waste algal biorefinery for bioenergy and biochar: A green leap towards
      achieving energy and environmental sustainability.
AB  - In spite of tremendous efforts and huge investments on resources, biodiesel from
      oleaginous microalgae has not yet become a commercially viable and sustainable
      alternative to petro-diesel. This is mainly because of the technological and
      economic challenges hovering around large scale cultivation and downstream
      processing of algae, water and land usage, stabilized production technology,
      market forces and government policies on alternative energy and carbon credits.
      This review attempts to capture and analyse the global trends and developments in
      the areas of biofuel and bio-product of microalgae and proposes possible
      strategies that can be adopted to produce biofuel, biochar and bio-products
      utilizing wastewater in a bio-refinery model. The strategies include "Zero waste
      discharge" concept with process integration, wherein microalgae is grown
      strategically using different wastewater combined with flue gas in cultivation
      system for simultaneous production of 'high-value-low-volume' product and 'low
      value-high-volume' product with sharing of the remnant biomass to produce
      biochar. In addition, the CO2 present in the atmosphere is captured and
      sequestered long term in the form of biochar would help to attain carbon
      negativity, while remediating wastewater and balancing energy requirements.
      Therefore, "Zero waste discharge" concept holds the potential to make the process
      a sustainable one, while gaining on the carbon credits.

PMID- 30293003
TI  - Investigation of environmental Kuznets curve for ecological footprint: The role
      of energy and financial development.
AB  - Climate change has become a global phenomenon due to its threat to sustainable
      development. However, economic development plays a complementary role in both
      climate change and sustainability. Thus, the environmental Kuznets curve
      hypothesis is critical to climate change policy formulation and development
      strategies. Accordingly, this study examined the validity of environmental
      Kuznets curve hypothesis by investigating the relationship between economic
      growth, energy consumption, financial development, and ecological footprint for
      the period from 1977 to 2013 in 11 newly industrialized countries. For this
      purpose, the study employed both augmented mean group (AMG) estimator and
      heterogeneous panel causality method which are suitable for dependent and
      heterogeneous panels. The results of the estimator show that there is an inverted
      U-shaped relationship between economic growth and ecological footprint. According
      to the causality test results, it is concluded that there is bi-directional
      causality between economic growth and ecological footprint.

PMID- 30293004
TI  - Eco-friendly non-biocide-release coatings for marine biofouling prevention.
AB  - Environmental concerns have been changing the way of looking for solutions to
      problems. The hydrosphere, together with its biosphere, has been feeling the
      impact of many pollutants, used for instance in the marine industry for economic
      reasons or lack of knowledge of their effects. In particular biocides, applied as
      coatings in paints, are released into the waters becoming toxic and persistent
      extending their action to an area far beyond the initial coated surface they
      should protect. In order to minimize these side effects, two biocides, Irgarol
      (I) and Econea (E), were covalently attached to polyurethane (PU) and foul
      release silicone based (PDMS) marine paints through an isocyanate linker. Their
      antifouling bioactivity was better in PDMS coatings, both for single (Econea) and
      combined biocides (E/I ratio = 1.5) with contents lower than 0.6 wt%. The treated
      samples remained almost clean after more than one year immersion in the
      Portuguese shore of the Atlantic Ocean, and after about 24 weeks under the
      tropical conditions of Singapore (Fouling rate < 1%). Complementary biofilm
      adhesion susceptibility tests against Pseudoalteromonas tunicata D2 showed
      adhesion reduction higher than 90% for PU formulations containing single biocides
      and close to 100% for PDMS with combined biocides. The eco-toxicity assessment
      evidenced a low environmental impact, in accordance with the European standards.
      In addition, shipping field trial tests showed the best antifouling performance
      for the Econea-based PDMS formulations (E = 0.6 wt%), which remained clean for
      about nine months in open seawaters, proving the efficacy of this non-release
      strategy, when applied under dynamic conditions.

PMID- 30293005
TI  - Organotin contamination in commercial and wild oysters from China: Increasing
      occurrence of triphenyltin.
AB  - Organotin contamination in marine environment has been a public concern for many
      years due to its adverse impacts on biota and human health. This study
      investigated levels, distribution and health risks of six organotin compounds:
      tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT), triphenyltin (TPhT),
      diphenyltin (DPhT) and monophenyltin (MPhT) in commercial and wild oysters in
      China. The total organotin in commercial oysters ranged from 251 to 1949 ng Sn g
      1 dw (dry weight) >. Two endocrine disruptors TBT and TPhT were detected in these
      samples with the highest level of 68.1 +/- 20.1 ng Sn g-1 dw and 747 +/- 7.3 ng
      Sn g-1 dw, respectively. For wild oysters, the concentrations of total organotins
      varied from 33.3 to 2671 ng Sn g-1 dw. Butyltins were dominated by TBT with the
      mean level of 26.1 +/- 30.0 ng Sn.g-1 dw and showed no significant spatial
      variation between the southern and northern coastal zones (p > 0.05). However,
      compared with the north, phenyltin levels especially TPhT were much higher in the
      south coastline (246-1484 ng Sn.g-1 dw) due to the wider use of TPhT-based
      biocides in local mariculture and agriculture. Health risk assessment indicated
      that a daily exposure of TPhT-contaminated oysters (including commercial and wild
      ones) may pose adverse threats to human particularly children as the risk
      quotients (RQ) were higher than 1. Organotin contamination (e.g., TPhT) still
      occurs in the South China's coastal zones after the TBT ban, which deserves
      future research and effective measures to protect the marine ecosystem and human
      health.

PMID- 30293006
TI  - Mercury and other trace metals in lettuce (Lactuca sativa) grown with two low
      salinity shrimp effluents: Accumulation and human health risk assessment.
AB  - Shrimp farming effluents from two sources of low-salinity water, well water (WW)
      and diluted seawater (DSW) (salinity, 1.7 g L-1; electrical conductivity, 2.7 dS
      m-1), were used to grow lettuce (L. sativa) in order to assimilate the nutrients
      present in shrimp effluents and produce edible biomass. The two treatments, WW
      and DSW, were tested in triplicate. Additionally, one hydroponic system in
      triplicate was constructed to grow lettuce using a nutritive solution as the
      control treatment (HS). The production variables of lettuce in the two crop
      varieties (Parris Island (VPI) and Tropicana M1 (VTM1)) showed a general trend of
      DSW > HS > WW with regards to the size, weight and total foliage, except for the
      number of leaves, which was higher with HS treatment than with WW and DSW
      treatments. The accumulation of Cu, Hg, Mn and Zn in edible lettuce tissue and
      the health risk by the intake of lettuce were evaluated. Heavy metal
      concentrations in edible lettuce tissue for the three treatments showed the same
      trend of Mn > Zn > Cu > Hg, with concentration ranges of 47.1 to 188.7, 35.7 to
      66.2, 4.1 to 6.4, and 0.01 to 0.02 mg kg-1 (dry weight), respectively. Such
      concentrations did not exceed the safe limits (CAC, 1984). The health risk index
      and target hazard quotient were <1, which indicates that the population exposed
      to these metals due to intake from lettuce consumption is unlikely to have
      adverse health effects when shrimp farming effluents are used to grow lettuce
      plants.

PMID- 30293007
TI  - Pollution characteristics in a dusty season based on highly time-resolved online
      measurements in northwest China.
AB  - To investigate the pollution characteristics and potential sources in a dusty
      season, an online analyzer was used to measure trace gases and major water
      soluble ions in PM10 from April 1st to May 29th, 2011 in Lanzhou. The average
      concentrations of HONO, HNO3, HCl, SO2 and NH3 were 0.93, 1.16, 0.48, 9.29 and
      5.54 MUg/m3, respectively, and 2.8, 2.76, 8.28 and 2.48 MUg/m3 for Cl-, NO3-,
      SO42- and NH4+. In the non-dust period, diurnal variations of SO42-, NO3- and
      their gaseous precursors showed similar change trend. NH4+ showed unimodal
      pattern whereas NH3 illustrated a bimodal pattern. HCl and Cl- showed an opposite
      diurnal pattern. In the dust event, temporal profiles of HCl and Cl-, SO2 and
      SO42- all presented similar change trend, and SO42- and Cl- preceded dust ions
      (Ca2+ and Mg2+) 13 h. The ratios of NO3- to SO42- were 0.65 in the non-dust
      period and 0.31 in the dust event. In the dust event, the sulfur oxidation ratio
      (SOR) was a factor of 1.33 greater than that in the non-dust period, and [SO42
      ]/[SO2] was 2.31 times of that in the non-dust period. The source apportionment
      using Probabilistic Matrix Factorization (PMF) suggested that fugitive dust
      (58.09%), secondary aerosols (33.98%), and biomass burning (7.93%) were the major
      sources in the non-dust period whereas dust (67.01%), salt lake (29.68%), biomass
      burning (0.8%), and motor vehicle (2.51%) were the primary sources in the dust
      event. Concentration weighted trajectory (CWT) model indicated that NO3-, Cl- and
      K+ could be regarded as local source species, the potential sources of Na+, Mg2+
      and Ca2+ concentrated in the two large areas with the one covered in the junction
      areas of Xinjiang, Qinghai and Gansu and another one covered the places around in
      Lanzhou, the potential sources of SO42- were mainly localized in the areas
      adjacent to Lanzhou.

PMID- 30293008
TI  - In situ generation of H2O2 using MWCNT-Al/O2 system and possible application for
      glyphosate degradation.
AB  - Hydrogen peroxide (H2O2), as a green oxidant, has been widely applied into
      advanced oxidation processes (AOPs) for the degradation of toxic organic
      pollutants. The in situ generation of H2O2 can not only improve the storage and
      transportation safety of H2O2 but also reduce the capital and operation costs. In
      the present work, a novel system, i.e., multi-walled carbon nanotube-aluminum
      (MWCNT-Al) composite was used to in situ generate H2O2 through micro
      electrolysis. The MWCNT-Al composite was characterized and optimized. The
      accumulation concentration of H2O2 reached 947 mg/L at the initial pH of 9.0, the
      MWCNT-Al composite dosage of 8 g/L and oxygen gas flow rate of 400 mL/min after
      60 min. The in situ generation of H2O2 was achieved by MWCNT-Al/O2 system, mainly
      owing to the direct contact between Al0 and MWCNT in MWCNT-Al composite, which
      accelerated the transfer of electrons from Al0 to O2, as well as the excellent
      electrocatalytic activity of MWCNT toward the two-electron reduction of oxygen.
      When H2O2 in situ generation technology was used in peroxone process (O3/H2O2
      process) to degrade glyphosate in aqueous solution, the removal efficiency of TOC
      and total phosphorus was 68.35% and 73.27%, respectively. Finally, the possible
      mechanism of in situ generation of H2O2 in MWCNT-Al/O2 system was temporarily
      proposed.

PMID- 30293009
TI  - Linking global climate change to local water availability: Limitations and
      prospects for a tropical mountain watershed.
AB  - Bridging the gap between the predictions of coarse-scale climate models and the
      fine-scale climatic reality is a key issue of hydrological research and water
      management. While many advances have been realized in developed countries, the
      situation is contrastingly different in most tropical regions where we still lack
      information on potential discrepancies between measured and modeled climatic
      conditions. Consequently, water managers in these regions often rely on non
      academic expertise to help them plan their future strategies. This issue is
      particularly alarming in tropical mountainous areas where water demand is
      increasing rapidly and climate change is expected to have severe impacts. In this
      article, we addressed this issue by evaluating the limitations and prospects in
      using regional climate models for evaluating the impact of climate change on
      water availability in a watershed that provides Quito, the capital of Ecuador,
      with about 30% of its current water needs. In particular, we quantified the
      temporal and spatial discrepancies between predicted and observed precipitation
      and temperature, and explored underlying mechanisms at play. Our results provide
      a strong critique of the inappropriate use of regional models to inform water
      planning with regard to adaptation strategies to face climate change. As a
      multidisciplinary group composed of hydrologists, ecologists and water managers,
      we then propose a framework to guide future climate change impact studies in
      tropical mountain watersheds where hydro-climatological data are scarce.

PMID- 30293010
TI  - Understanding the global hydrological droughts of 2003-2016 and their
      relationships with teleconnections.
AB  - Droughts often evolve gradually and cover large areas, and therefore, affect many
      people and activities. This motivates developing techniques to integrate
      different satellite observations, to cover large areas, and understand spatial
      and temporal variability of droughts. In this study, we apply probabilistic
      techniques to generate satellite derived meteorological, hydrological, and hydro
      meteorological drought indices for the world's 156 major river basins covering
      2003-2016. The data includes Terrestrial Water Storage (TWS) estimates from the
      Gravity Recovery And Climate Experiment (GRACE) mission, along with soil
      moisture, precipitation, and evapotranspiration reanalysis. Different drought
      characteristics of trends, occurrences, areal-extent, and frequencies
      corresponding to 3-, 6-, 12-, and 24-month timescales are extracted from these
      indices. Drought evolution within selected basins of Africa, America, and Asia is
      interpreted. Canonical Correlation Analysis (CCA) is then applied to find the
      relationship between global hydro-meteorological droughts and satellite derived
      Sea Surface Temperature (SST) changes. This relationship is then used to extract
      regions, where droughts and teleconnections are strongly interrelated. Our
      numerical results indicate that the 3- to 6-month hydrological droughts occur
      more frequently than the other timescales. Longer memory of water storage changes
      (than water fluxes) has found to be the reason of detecting extended hydrological
      droughts in regions such as the Middle East and Northern Africa. Through CCA, we
      show that the El Nino Southern Oscillation (ENSO) has major impact on the
      magnitude and evolution of hydrological droughts in regions such as the northern
      parts of Asia and most parts of the Australian continent between 2006 and 2011,
      as well as droughts in the Amazon basin, South Asia, and North Africa between
      2010 and 2012. The Indian ocean Dipole (IOD) and North Atlantic Oscillation (NAO)
      are found to have regional influence on the evolution of hydrological droughts.

PMID- 30293011
TI  - Characterization of water soluble inorganic ions and their evolution processes
      during PM2.5 pollution episodes in a small city in southwest China.
AB  - PM2.5 samples were collected in four segregate one-month periods, each
      representing one season, for analyzing their contents of water soluble inorganic
      ions (WSIIs) in a small city inside Sichuan Basin. Daily PM2.5 concentrations
      ranged from 23.2 to 203.1 MUg m-3 with an annual mean of 66.9 +/- 33.6 MUg m-3.
      Annual mean concentrations of WSIIs was 28.8 +/- 20.3 MUg m-3, accounting for
      43.1% of PM2.5. Seasonal mean concentrations of WSIIs ranged from 17.5 +/- 9.3
      MUg m-3 in summer to 46.5 +/- 27.6 MUg m-3 in winter. Annual mean mass ratio of
      NO3-/SO42- was 0.49, demonstrating predominant stationary sources for secondary
      inorganic aerosols (SNA, including SO42-, NH4+ and NO3-); whereas annual mean
      molar ratio of [NH4+]/[NO3-] was 3.5, suggesting dominant agriculture emissions
      contributing to the total nitrogen. During a severe and long-lasting (13 days)
      winter pollution period when mean PM2.5 concentration reached to 132.5 MUg m-3,
      PM2.5 concentration was enhanced by a factor of 2.6 while that of SNA by a factor
      of 2.9 compared to those before the pollution event, and the fraction of SNA in
      PM2.5 only increased slightly (from 46.7% to 50.6%). Thus, local accumulation of
      pollutants under poor diffusion conditions played a major role causing the
      extremely high PM2.5 concentration, besides the contributions from the enhanced
      SNA formation under specific weather conditions.

PMID- 30293013
TI  - The role of gender in the structure of networks of childhood adversity.
AB  - The objective of present study is to investigate the relationship between
      different childhood adversities. The potential impact of early adversity on
      prevention programs is discussed. Data on twelve childhood adversities was
      collected from a representative sample of 5037 members of the general population
      living in a large metropolitan area. Data were analyzed through network analysis,
      to estimate and compare network connectivity and centrality measures by gender.
      Over half the respondents had been exposed to at least one adversity during their
      earlier developmental stage. Among adversity-exposed persons, 48.4% presented
      simultaneous adversities, most of which were related to 'family dysfunction' and
      'maltreatment' (mean = 2.9 adversities). Women reported more adversities than men
      (59.0% vs. 47.6%). Although the 'global' network connectivity across adversities
      was similar in both genders, 'regional' distinctions in the network structure
      were found. While 'neglect' and 'parental death' were more important for women
      than men, 'parental mental disorders' was more important for men. Gender-related
      childhood adversities were clustered experiences. Adversities related to 'early
      family dysfunction' and 'maltreatment' were prominent features in the networks of
      both boys and girls. Differential preventive and intervention programs should
      take into account gender-related patterns of exposure and reporting patterns of
      early adversity.

PMID- 30293012
TI  - M1 Macrophage Polarization Is Dependent on TRPC1-Mediated Calcium Entry.
AB  - Macrophage plasticity is essential for innate immunity, but in-depth signaling
      mechanism(s) regulating their functional phenotypes are ill-defined. Here we
      report that interferon (IFN) gamma priming of naive macrophages induces store
      mediated Ca2+ entry and inhibition of Ca2+ entry impairs polarization to M1
      inflammatory phenotype. In vitro and in vivo functional analyses revealed ORAI1
      to be a primary contributor to basal Ca2+ influx in macrophages, whereas IFNgamma
      induced Ca2+ influx was mediated by TRPC1. Deficiency of TRPC1 displayed
      abrogated IFNgamma-induced M1 inflammatory mediators in macrophages. In a
      preclinical model of peritonitis by Klebsiella pneumoniae infection, macrophages
      showed increased Ca2+ influx, which was TRPC1 dependent. Macrophages from
      infected TRPC1-/- mice showed inhibited expression of M1-associated signature
      molecules. Furthermore, in human patients with systemic inflammatory response
      syndrome, the level of TRPC1 expression in circulating macrophages directly
      correlated with M1 inflammatory mediators. Overall, TRPC1-mediated Ca2+ influx is
      essential for the induction/shaping of macrophage polarization to M1 inflammatory
      phenotype.

PMID- 30293014
TI  - Psychomotor agitation in subjects hospitalized for an acute exacerbation of
      Schizophrenia.
AB  - The aims of this study were to establish the prevalence of moderate and severe
      psychomotor agitation in patients hospitalized for an active phase of
      schizophrenia, the associations between psychomotor agitation and patients'
      demographic and clinical variables, the intra-individual stability of the
      agitated/non-agitated dichotomy in independent psychotic breakdowns. The study
      was performed on a database relative to 630 inpatients hospitalized with a
      diagnosis of schizophrenia. Psychomotor agitation was measured with the Positive
      and Negative Syndrome Scale - Excited Component (PANSS-EC). Prevalence of
      moderate and severe psychomotor agitation was 40.5% and 23.7%, respectively. Non
      agitated patients were older, with longer illness history and duration of
      untreated psychosis, were more frequently on antipsychotic medication, had lower
      incidence of recent use of substances, and functioned better before the index
      hospitalization than moderately and/or severely agitated patients. Non-agitated
      patients had lower scores for total PANSS and Emsley's positive and anxiety
      dimensions. Compared with the severely agitated group, non-agitated and
      moderately agitated patients scored more in Emsley's depression dimension. Poor
      functioning before index hospital admission, higher scores for negative subscale
      and Emsley's positive dimension and use of substances exerted an effect on risk
      of psychomotor agitation.

PMID- 30293016
TI  - PHACTR1 regulates oxidative stress and inflammation to coronary artery
      endothelial cells via interaction with NF-kappaB/p65.
AB  - BACKGROUND AND AIMS: Genome-wide association studies have showed that genetic
      variants in phosphatase and actin regulator 1 (PHACTR1) are associated with
      coronary artery disease and myocardial infarction. However, the underlying
      mechanism of PHACTR1 in atherosclerosis remains unknown. METHODS: Immunoblots
      were performed to evaluate the expression of PHACTR1 and phosphorylation of NF
      kappaB signaling. Reactive oxygen species (ROS) labeled with DCFH-DA were
      assessed by flow cytometry. Fluorescence microscope was used to detect the
      translocation of p65 in human coronary artery endothelial cells (HACECs). Co
      immunoprecipitation was performed to determine the interaction of PHACTR1 with
      MRTF-A. RESULTS: The mRNA and protein levels of PHACTR1 were markedly increased
      in carotid plaquescompared with normal carotid arteries. Immunofluorescence
      staining indicated that PHACTR1 was constitutively expressed in endothelial cells
      in carotid plaques. Knockdown of PHACTR1 reduced excessive ICAM-1, VCAM-1 and VE
      cadherin expression induced by oxidized low density lipoprotein (ox-LDL) in
      HCAECs. Additionally, silencing PHACTR1 alleviated p47phox phosphorylation and
      intracellular oxidative stress reflected by the reduction of ROS. Molecular
      experiments revealed that knockdown of PHACTR1 attenuated NF-kappaB activity
      without affecting IkappaBalpha and IKKalpha/beta phosphorylation. In contrast,
      nuclear translation of p65 was blocked by depletion of PHACTR1. Furthermore, co
      immunoprecipitation showed that PHACTR1 interacted with MRTF-A and p65 in HCAECs.
      Knockdown of MRTF-A suppressed the interaction of PHACTR1 with p65, subsequently
      blocking the nuclear translocation of p65. CONCLUSIONS: Our finding suggest that
      silencing PHACTR1 alleviates the nuclear accumulation of p65 and NF-kappaB via
      interaction with MRTF-A, ensuing attenuating oxidative stress and inflammation in
      HCAECs.

PMID- 30293015
TI  - Associations between prenatal maternal urinary concentrations of personal care
      product chemical biomarkers and childhood respiratory and allergic outcomes in
      the CHAMACOS study.
AB  - BACKGROUND: Personal care product chemicals may be contributing to risk for
      asthma and other atopic illnesses. The existing literature is conflicting, and
      many studies do not control for multiple chemical exposures. METHODS: We
      quantified concentrations of three phthalate metabolites, three parabens, and
      four other phenols in urine collected twice during pregnancy from 392 women. We
      measured T helper 1 (Th1) and T helper 2 (Th2) cells in their children's blood at
      ages two, five, and seven, and assessed probable asthma, aeroallergies, eczema,
      and lung function at age seven. We conducted linear and logistic regressions,
      controlling for additional biomarkers measured in this population as selected by
      Bayesian Model Averaging. RESULTS: The majority of comparisons showed null
      associations. Mono-n-butyl phthalate (MnBP) was associated with higher Th2% (RR:
      10.40, 95% CI: 3.37, 17.92), and methyl paraben was associated with lower Th1%
      (RR: -3.35, 95% CI: -6.58, -0.02) and Th2% at borderline significance (RR: -4.45,
      95% CI: -8.77, 0.08). Monoethyl phthalate was associated with lower forced
      expiratory flow from 25 to 75% of forced vital capacity (FEF25-75%) (RR: -3.22
      L/s, 95% CI: -6.02, -0.34). Propyl paraben (OR: 0.86, 95% CI: 0.74, 0.99) was
      associated with decreased odds of probable asthma. CONCLUSIONS: While some
      biomarkers, particularly those from low molecular weight phthalates, were
      associated with an atopic cytokine profile and poorer lung function, no
      biomarkers were associated with a corresponding increase in atopic disease.

PMID- 30293017
TI  - A facility location problem for sustainability-conscious power generation
      decision makers.
AB  - The practical implementation of a performance measurement system is an inevitable
      necessity for all levels of management to direct business operations towards
      maximal efficiency. In particular, academics' and practitioners' expectations
      have resulted in notable initiatives that incorporate sustainability assessment
      in managerial decision-making. The sustainability paradigm investigates practices
      and policies that simultaneously account for economic, environmental, and social
      aspects. Drawing on the perspective of a sustainability-conscious decision maker,
      this paper centers on the evaluation of logistical locations with capacitated
      production levels through a two-phase assessment procedure. To design a
      supervisory framework to measure the sustainability performance of the supplying
      facilities under investigation, we develop a double bootstrap data envelopment
      analysis model with undesirable factors in the first phase. We, then, use the
      obtained bias-corrected efficiency estimates in the second phase to establish
      sustainability-based policies in the context of facility location problems. The
      proposed model is applied to an energy case study of fossil fuel power plants in
      the United States. We present empirical evidence corroborating a considerable
      difference between the results of the case where the decision maker explores the
      environmental and social impacts of the power plants and the conventional
      formulation by which only financial outcomes are considered. Our numerical
      findings reveal that the proposed approach substantially diminishes greenhouse
      gas emissions at the cost of slight increases in total expenses. In addition to
      such an improvement in the environmental efficiency, we provide evidence of a
      dramatic enhancement in the social performance.

PMID- 30293018
TI  - Improving nature experience in cities: What are people's preferences for
      vegetated streets?
AB  - In the current context of strong urban sprawl, it becomes urgent to find urban
      approaches that simultaneously promote ecological functions and relationships
      between people and nature in cities. Streets are omnipresent urban elements that
      can deliver ecosystem services and facilitate people daily interactions with
      nature. Promoting vegetation in streets can take different forms which have to be
      combined with people's preferences. Based on photomontages, we assessed people's
      perceptions and valuations for herbaceous vegetation types associated to various
      managements and designs of pavements. Using a combination of a local field survey
      and a French national online survey, we collected a total of 3609 responses
      representing a large diversity of socio-demographic characteristics. The results
      of the field survey confirmed those of the online survey. Although there was
      variability among people valuations, we found that lowly managed pavements with
      spontaneous vegetation were in average higher valued than highly managed
      pavements without vegetation. Pavements with spontaneous vegetation were
      perceived as less kept than pavements without vegetation, but more beautiful and
      less boring. We found a consensus of high valuations towards pavements containing
      vegetation integrated in small design interventions (flowers seeded in foot of
      wall, design of a meadow strip along the pavement), suggesting that people
      generally accept vegetation with visible signs of human actions or managements.
      Socio-demographic characteristics partly explained variabilities in photo
      valuations. As expected, people frequently connected with nature had the highest
      preferences for vegetated pavements, spontaneous or integrated in designs. These
      results show that vegetated streets can become daily biodiversity-friendly urban
      greenspaces appreciated by urban dwellers. We provide recommendations for
      promoting vegetation in streets that will be useful for politics, urban designers
      and managers.

PMID- 30293019
TI  - Countries' classification by environmental resilience.
AB  - Rapid population growth, urbanization, and industrialization affect countries'
      vulnerability to future disasters. This study investigates the vulnerability of
      141 countries to natural and anthropogenic hazards using six environmental
      indicators including air pollution, greenhouse gas (GHG) emissions, access to
      drinking water, access to improved sanitation, environmental risks (total death
      and affected people), and energy use. Results confirm that the resilience varies
      by the location. Furthermore, this work delineates the World countries using the
      environmental resilience score. The most resilient countries are located in
      Europe and North America and the least resilient countries are in Africa and
      Asia. Based on the results, Estonia and Ethiopia are the most and the least
      resilient countries, respectively. Integrated results can highlight resilient
      cities as a guide for other regions.

PMID- 30293020
TI  - Influential parameters on natural weathering under harsh climatic conditions of
      mechanically recycled plastic film specimens.
AB  - In this work, real life reclaimed plastic solid waste (PSW) secured from the
      municipal sector was mechanically recycled and compounded with virgin linear low
      density polyethylene (LLDPE). The compounding of the plastic film samples
      utilised the means of extrusion and blown filming to produce various formulations
      of the blends containing up to 100% (by weight) of the PSW in the examined
      specimens. The film samples were compared to market products used in the State of
      Kuwait where PSW accumulation presents a major obstacle. Natural weathering under
      arid and harsh climatic conditions was also performed to determine the
      degradation extent of the film samples. Haze (%), light transmission (%) and the
      total change in colour (DeltaE) were measured as indicators to the degradation
      profile of the polymeric materials, in addition to tensile pull mechanical
      properties. Properties were noted to deteriorate as a function of weathering time
      and waste content. Statistical analysis was also performed on the properties
      measured and climatic conditions including airborne pollutants levels. The
      abundance of the secondary airborne pollutant (ozone) was determined to be a
      significant variable on the studied properties. This can be attributed to induced
      photo-oxidation the polymeric matrix is subjected to under such climatic
      conditions which increases oxygen diffusion throughout the polymeric matrix.
      Future development of the recycled blends studied in this work can be a route for
      the decrease of associated environmental stressors with virgin plastic resin
      conversion.

PMID- 30293021
TI  - Introduction of the circular economy within developing regions: A comparative
      analysis of advantages and opportunities for waste valorization.
AB  - The introduction of effective solid waste management strategies in developing
      countries should be considered for improving sustainability at global level. Many
      barriers should be overcome, concerning the introduction of environmental
      policies, effective investments, social inclusion and public awareness, which are
      significant issues in low-middle income countries. The Circular Economy could
      represent the answer for improving current solid waste management activities
      worldwide, since denote the principle of waste valorization and recycling for
      boosting developing economies. This paper is focused on this theme, analyzing
      main opportunities for improving the current state of solid waste management in
      developing big cities. The solid waste management of two countries are reviewed:
      Romania is the emerging country where Circular Economy is becoming a future
      objective due to economic aids and strength regulations which the European Union
      (EU) established for the nations forming parts the alliance; as a comparison,
      Bolivia is reported for evaluating main differences founded for developing
      recycling systems in a no-EU country. These two case studies could be of interest
      for highlighting main pros and cons of the participation into a wide organization
      like the EU for introducing in short terms Circular Economy principles. Moreover,
      a theoretical Circular Economy model for developing big cities in low-middle
      income countries is described within the study for effectively comparing which
      chances can spread for these countries as regard municipal solid waste
      exploitation. Despite the economic level, Romania and Bolivia are both facing
      with many solid waste management issues although in different magnitude. For the
      Romanian case study, it is visible how it cannot achieve the European goals for
      2020 due the need of change in public recycling behavior. Bolivia, instead,
      represents the case where international aids and new investments are required,
      considering the informal sector into the formal management system as a real
      opportunity for improving local recycling rate. In conclusion, the comparison
      suggests how external supports led to implement the principles of the Circular
      Economy within a developing region. The model of Circular Economy proposed is
      recommended for developing big cities in order to advance a new form of safe
      employment, encouraging the activities that are still in action (i.e. informal
      sector) and boosting the principles of sustainable development.

PMID- 30293022
TI  - Determinants of perceived risk and liability concerns associated with prescribed
      burning in the United States.
AB  - While prescribed burning is a proven tool in the management of forests and
      grasslands, its use has been limited due, in part, to potential risks that may
      result in legal liability, property damage, and personal injury. The purpose of
      this study is to understand the factors that shape landowners' and fire
      professionals' perceptions of risks associated with prescribed burning
      activities. The data for this study were collected from active prescribed fire
      professionals involved in Prescribed Burn Association (PBA) activities in 14
      Southern and Mid-western states. Perceived risk was higher among respondents with
      higher levels of concern related to safety and weather but lower among
      respondents with more experience in burning activities. Sociodemographic
      variables such as age and income were not significantly correlated with risk
      perception. These findings are useful for better understanding how landowners and
      fire professionals perceive risk and offer insight into how perceived risk
      affects decisions to apply prescribed burns.

PMID- 30293023
TI  - Elimination kinetics and detoxification mechanisms of microcystin-LR during
      UV/Chlorine process.
AB  - Microcystin-LR (MC-LR), a toxin produced by cyanobacteria, is very toxic and
      poses a threat to public health when entering water treatment works. In this
      study, UV/chlorine process, as an advanced oxidation process (AOP), has been
      demonstrated for effective elimination of MC-LR levels and associated toxicity.
      At a chlorine dose of 3.0 mg L-1 and UV fluence of 125 mJ cm-2, MC-LR (initial
      concentration 1.0 MUM) was reduced by 92.5%, which was much higher than 20.3%
      removal under UV irradiation alone and 65.1% removal during dark chlorination.
      Enhanced degradation was attributed by hydroxyl radicals (HO) and reactive
      chlorine species (RCS), mainly Cl2- and ClO. Increasing chlorine doses or
      lowering pH favored MC-LR removal. Increased bicarbonate and natural organic
      matter concentrations inhibited MC-LR removal, but bromide ions enhanced MC-LR
      removal instead. MC-LR elimination rates in natural waters were roughly two times
      smaller than those in ultrapure water. The reactive radicals promoted
      hydroxylation of both diene of Adda moiety and double bond of Mdha moiety in MC
      LR. UV exposure enhanced the dechlorination of chloro-MC-LR via the cleavage of
      CCl bond. The toxicity was evaluated by a protein phosphatase (PP2A) inhibition
      assay. At a chlorine dose of 3.0 mg L-1 and UV fluence of 125 mJ cm-2, the
      toxicity of the treated water was reduced by 75.0%, which was also higher than
      25.7% and 46.7% removal under UV irradiation alone and during dark chlorination,
      respectively. These results highlight UV/chlorine is an efficient AOP for MC-LR
      degradation and detoxification.

PMID- 30293024
TI  - Organic contaminated sediments remediation with active caps: Nonlinear adsorption
      unveiled by combined isotherm and column transportation studies.
AB  - Bench-scale column studies were performed with four cap materials (sand, apatite,
      organoclay and granular activated carbon) for five target compounds (toluene,
      naphthalene, phenanthrene, pyrene and dichlorobiphenyl) to represent a range of
      cap materials and pollutants (volatile & semi-volatile compounds) commonly found
      in sediments. Two moment-derived methods were used to model cap performance.
      Rough agreement was observed between the column experiments and modeling data
      with the fronting and tailing effects identified from certain breakthrough curves
      indicating a high potential of non-linear adsorption. Distribution coefficients
      (kd) were experimentally determined with isotherm studies together with
      measurements of surface area and microporosity of the cap materials via nitrogen
      adsorption porisimetry. These studies unveiled the occurrence of nonlinear
      adsorption by Freundlich simulation. The effects of nonlinear adsorption of the
      cap were further explored via modeling. Results suggested better prediction of
      cap performance assuming nonlinear adsorption instead of linear adsorption
      results based upon the risk of release for a 30-year period.

PMID- 30293025
TI  - Biodegradation study of methadone by adapted activated sludge: Elimination
      kinetics, transformation products and ecotoxicological evaluation.
AB  - The biotransformation study of difficult-to-degrade opioid analgesic methadone
      (MTHD) was performed by activated sludge culture adapted to high concentration of
      methadone (10 mg/L). The study included determination of elimination kinetics of
      the parent compound, taxonomic characterization of microbial culture,
      identification of biotransformation products (TPs) and assessment of
      ecotoxicological effects of biotransformation processes. The chemical analyses
      were performed by ultra-performance liquid chromatography/quadrupole-time-of
      flight mass spectrometry, whereas the ecotoxicological assessment was made based
      on determinations of toxicity to freshwater algae. Changes of the adapted sludge
      culture during the experiment were followed using the 16S rRNA gene amplicon
      sequencing. Depending on the experimental conditions, the elimination efficiency
      of methadone (10 mg/L) varied from 9% to 93% with the corresponding half-lives
      from 11.4 days to 1.5 days. A significantly faster elimination (t1/2 from 1.5
      days to 5.8 days) was achieved at cometabolic conditions, using glucose
      containing media, as compared to the experiments with MTHD as a single organic
      carbon source (t1/2 = 11.4 days). Moreover, increased biotransformation rate
      following the additional supplementation of ammonia, revealed a possible
      importance of nitrogen availability for the transformation at cometabolic
      conditions. The elimination of parent compound was associated with the formation
      of 3 different TPs, two of which were identical to main human metabolites of
      MTHD, 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5
      methyl-3,3-diphenyl-1-pyrroline (EMDP). EDDP represented over 90% of the total TP
      concentration at the end of experiment. The biodegradation of MTHD was associated
      with a pronounced drop in algal toxicity, confirming a rather positive
      ecotoxicological outcome of the achieved biotransformation processes.

PMID- 30293026
TI  - Deep seepage of per- and polyfluoroalkyl substances through the soil of a
      firefighter training site and subsequent groundwater contamination.
AB  - Per- and polyfluoroalkyl substances (PFASs) are utilized in specific firefighting
      foams. The objectives of this study were i) to map PFAS distribution in the soil
      and groundwater of a firefighter training site active for more than 3 decades,
      ii) to locate the main points of entry of PFASs into the aquifer and iii) to
      identify which PFASs seeped most deeply into the soil. A total of 44 soil cores
      and 17 groundwater samples were collected. Perfluorooctane sulfonate (PFOS), 6:2
      fluorotelomer sulfonic acid (6:2 FTSA) and 6:2 Fluorotelomer sulfonamide
      alkylbetaine (6:2 FTAB) were the most predominant PFASs in surface soil. The
      highest total PFAS concentrations (up to 357 MUg/g) were measured in two areas.
      Both areas were considered as potential points of entry of PFASs into the aquifer
      since PFASs were detected in soil 15 m below the surface, despite the presence of
      clay layers. The highest total PFAS concentrations were recorded in the
      monitoring wells located in the perimeter of the firefighter training site and in
      the spring located downgradient in the direction of groundwater flow. They ranged
      from 300 to 8300 ng/L. The fluorotelomer 6:2 FTAB was quantified in 6 monitoring
      wells, suggesting that this FT can reach a water table 20 m below the ground's
      surface.

PMID- 30293027
TI  - A biomimetic SiO2@chitosan composite as highly-efficient adsorbent for removing
      heavy metal ions in drinking water.
AB  - Highly efficient adsorbents for drinking water purification are demanded since
      the contaminants are generally in a low concentration which makes it difficult
      for conventional adsorbents. Herein, we present a novel biomimetic SiO2@chitosan
      composite as adsorbent with a high adsorption capability towards heavy metal ions
      including As(V) and Hg(II). The hollow leaf-like SiO2 scaffold within the
      adsorbent has a stable chemical property; while on the surface SiO2, the chitosan
      nanoparticle provide a large amount of active sites such as amino and hydroxyl
      groups for adsorbing heavy metal ions. The special SiO2 structure also prevents
      the agglomeration and loss of chitosan, which enables the efficient contact
      between the functional groups of chitosan and heavy metal ions. The SiO2@chitosan
      composite exhibits maximum adsorption capacities of 204.1 and 198.6 mg g-1
      towards Hg(II) and As(V), respectively. In addition, the removal efficiency
      reaches over 60% within 2 min. The adsorption performance enables the presented
      biomimetic adsorbent suitable for adsorbing low-concentration heavy metal ions,
      especially possessing a promising potential for drinking water purification.

PMID- 30293028
TI  - Designing biochar properties through the blending of biomass feedstock with
      metals: Impact on oxyanions adsorption behavior.
AB  - Metal-blending of biomass prior to pyrolysis is investigated in this work as a
      tool to modify biochar physico-chemical properties and its behavior as adsorbent.
      Six different compounds were used for metal-blending: AlCl3, Cu(OH)2, FeSO4, KCl,
      MgCl2 and Mg(OH)2. Pyrolysis experiments were performed at 400 and 700  degrees C
      and the characterization of biochar properties included: elemental composition,
      thermal stability, surface area and pore size distribution, Zeta potential, redox
      potential, chemical structure (with nuclear magnetic resonance) and adsorption
      behavior of arsenate, phosphate and nitrate. Metalblending strongly affected
      biochars' surface charge and redox potential. Moreover, it increased biochars'
      microporosity (per mass of organic carbon). For most biochars, mesoporosity was
      also increased. The adsorption behavior was enhanced for all metal-blended
      biochars, although with significant differences across species: Mg(OH)2-blended
      biochar produced at 400  degrees C showed the highest phosphate adsorption
      capacity (Langmuir Qmax approx. 250 mg g-1), while AlCl3-blended biochar produced
      also at 400  degrees C showed the highest arsenate adsorption (Langmuir Qmax
      approx. 14 mg g-1). Significant differences were present, even for the same
      biochar, with respect to the investigated oxyanions. This indicates that biochar
      properties need to be optimized for each application, but also that this
      optimization can be achieved with tools such as metal-blending. These results
      constitute a significant contribution towards the production of designer
      biochars.

PMID- 30293029
TI  - Bioethanol production from palm wood using Trichoderma reesei and Kluveromyces
      marxianus.
AB  - In the present work, palm wood was pretreated using hydrothermal technique in
      conjunction with chemical method for removal of lignin. Pretreated palm wood was
      subjected to hydrolysis using Trichoderma reesei MTCC 4876. Subsequently
      bioethanol was produced using palm wood hydrolysate by Kluveromyces marxianus
      MTCC 1389. RSM was used to identify the non-linear relationship and optimize
      various process parameters such as parameters such as pH, temperature, agitation
      rate, substrate concentration and inoculum size for bioethanol production. ANN
      constructed with 5-2-1 topology was also used to optimize process parameters. The
      experimental bioethanol yield of 22.90 g/l was obtained at ANN optimum conditions
      of temperature 45  degrees C, agitation rate 156 rpm, pH 5, substrate
      concentration 8% (v/v) and inoculum size 3.2% (v/v).

PMID- 30293030
TI  - Characterization of aerobic granular sludge used for the treatment of petroleum
      wastewater.
AB  - The application of aerobic granular sludge (AGS) is a promising biological method
      for wastewater treatment. In the present study, the AGS method was used for the
      treatment of petroleum wastewater. The granulation process and organic/nitrogen
      compound removal efficiencies were determined and correlated with the
      microbiological communities. Granulation of the aerobic sludge occurred after 35
      days of operation. The compacted granules had a diameter of 0.46-0.9 mm.
      Extracellular polymeric substances (EPS) contents increased as granulation
      progressed and reached 128 mg/g.VSS. The granulated sludge efficiently reduced
      COD by 95% and petroleum compound contents by 90%. NH4+-N and TN removal were
      inefficient due to the inhibition of nitrobacteria and denitrificans, but were
      significantly improved by the addition of glucose. The microorganisms in the
      granules capable of degrading petroleum chemicals consisted of the genera
      Propioniciclava, Micropruina, Alphaproteobacteria, Flavobacterium, and
      Sulfuritalea.

PMID- 30293031
TI  - A promising laccase immobilization approach for Bisphenol A removal from aqueous
      solutions.
AB  - The immobilization of crude laccase from Trametes pubescens by glutaraldehyde
      crosslinking prior to entrapment into Ca-alginate beads increased the
      immobilization yield by 30% and reduced the leaking by 7-fold compared to the
      immobilization with no crosslinking. The performance of the newly developed
      biocatalyst to degrade Bisphenol A (BPA) from aqueous solutions was tested. Thus,
      operating at optimal conditions (i.e. pH 5, 30  degrees C, 20 mg L-1 BPA and 1500
      U L-1 laccase), a BPA removal higher than 99% in 2 h was achieved. This value is
      higher than those reported to date for BPA removal by immobilized laccases. In
      addition, the biocatalyst was able to remove BPA in 10 successive batches with an
      efficiency higher than 70% at the end of the last batch. BPA adsorption on the
      alginate beads was negligible, therefore BPA removal was only due to laccase
      action. Moreover, Fourier-transform Infrared (FTIR) spectroscopy suggested BPA
      transformation by laccase.

PMID- 30293032
TI  - Targeted knockout of phospholipase A2 to increase lipid productivity in
      Chlamydomonas reinhardtii for biodiesel production.
AB  - Biofuel derived from microalgae have several advantages over other oleaginous
      crops, however, still needs to be improved with its cost aspect and can be
      achieved by developing of a strain with improved lipid productivity. In this
      study, the CRISPR-Cas9 system was incorporated to carry out a target-specific
      knockout of the phospholipase A2 gene in Chlamydomonas reinhardtii. The targeted
      gene encodes a key enzyme in the Lands cycle. As a result, the mutants showed a
      characteristic of increased diacylglycerol pool, followed by a higher
      accumulation of triacylglycerol without being significantly compensated with the
      cell growth. As a result, the overall lipid productivities of phospholipase A2
      knockout mutants have increased by up to 64.25% (to 80.92 g L-1 d-1). This study
      can provide crucial information for the biodiesel industry.

PMID- 30293033
TI  - Effects of biochar size and type on gaseous emissions during pig manure/wheat
      straw aerobic composting: Insights into multivariate-microscale characterization
      and microbial mechanism.
AB  - Greenhouse gas and ammonia emissions during composting with different biochar
      types and particle sizes were investigated. Compared with powder-biochar,
      granular-biochar improved pore connectivity and was benefit to methanotrophs
      activities, like Methylococcaceae, reducing CH4 emissions. At the same particle
      size, bamboo biochar (BB) had a higher pore volume and more aerobic
      microenvironment within the compost than rice straw biochar (RSB), reducing GHG
      emissions. Bamboo biochar had high aromatic compound and NO3- concentrations and
      therefore surface pi-pi electron donor/acceptor interactions, causing low N2O
      emissions and inhibiting denitrifying bacteria (e.g., Bacteroidales). More CO and
      CO bonds in rice straw biochar than bamboo biochar caused lower NH3 emissions
      using rice straw than bamboo biochar. Powdered biochar had more exposed reactive
      functional groups and decreased NH3 production better than granular biochar.
      Powdered bamboo biochar controls gaseous emissions better than other biochars
      during aerobic pig manure/wheat straw composting.

PMID- 30293034
TI  - The study of exercise tests in paroxysmal kinesigenic dyskinesia.
AB  - OBJECTIVE: To unravel if there was muscular ion channel dysfunction in paroxysmal
      kinesigenic dyskinesia (PKD) patients using the exercises tests (ET). METHODS:
      Sixty PKD patients including 28 PRRT2 mutations carriers were enrolled in this
      study, as well as 19 hypokalaemic periodic paralysis (HypoPP) patients as the
      positive controls and 45 healthy subjects as the negative controls. ET including
      long exercise test (LET) and short exercise test (SET) was performed in the
      corresponding subjects. RESULTS: In the LET, both the overall PKD patients and
      HypoPP patients had greater CMAP amplitude and area increments during exercise
      than healthy controls. At most 25% of PKD patients were identified from the
      normality with greater amplitude increment than the area. On the contrary, 50% of
      HypoPP patients were differentiated with greater area increment than the
      amplitude. More percentage of PRRT2- patients than PRRT2+ patients had abnormal
      average amplitude increment. Unexpectedly, five PKD patients had abnormal maximum
      CMAP amplitude decrements after exercise in the LET, and one had abnormal maximum
      immediate amplitude decrement in the SET. CONCLUSIONS: Distinct ET manifestations
      were found in PKD patients compared to normal controls and HypoPP patients.
      SIGNIFICANCE: Abnormal muscle membrane excitability might be involved in the
      mechanisms responsible for PKD.

PMID- 30293035
TI  - Chronic exposure to copper and zinc induces DNA damage in the polychaete Alitta
      virens and the implications for future toxicity of coastal sites.
AB  - Copper and zinc are metals that have been traditionally thought of as past
      contamination legacies. However, their industrial use is still extensive and
      current applications (e.g. nanoparticles and antifouling paints) have become
      additional marine environment delivery routes. Determining a pollutant's
      genotoxicity is an ecotoxicological priority, but in marine benthic systems
      putative substances responsible for sediment genotoxicity have rarely been
      identified. Studies that use sediment as the delivery matrix combined with
      exposures over life-history relevant timescales are also missing for metals. Here
      we assess copper and zinc's genotoxicity by exposing the ecologically important
      polychaete Alitta virens to sediment spiked with environmentally relevant
      concentrations for 9 months. Target bioavailable sediment and subsequent
      porewater concentrations reflect the global contamination range for coasts,
      whilst tissue concentrations, although elevated, were comparable with other
      polychaetes. Survival generally reduced as concentrations increased, but monthly
      analyses show that growth was not significantly different between treatments. The
      differential treatment mortality may have enabled the surviving worms in the high
      concentration treatments to capture more food thus removing any concentration
      treatment effects for biomass. Using the alkaline comet assay we confirm that
      both metals via the sediment are genotoxic at concentrations routinely found in
      coastal regions and this is supported by elevated DNA damage in worms from field
      sites. However, combined with the growth data it also highlights the tolerance of
      A. virens to DNA damage. Finally, using long term (decadal) monitoring data we
      show stable or increasing sediment concentrations of these metals for many areas.
      This will potentially mean coastal sediment is a significant mutagenic hazard to
      the benthic community for decades to come. An urgent reappraisal of the current
      input sources for these 'old pollutants' is, therefore, required.

PMID- 30293036
TI  - Spatial and temporal variations of bulk and colloidal dissolved organic matter in
      a large anthropogenically perturbed estuary.
AB  - In the present study, we characterized the sources of dissolved organic matter
      (DOM) and the processes controlling the evolution of DOM in a large
      anthropogenically perturbed estuary in Southern China. Three-dimensional
      excitation emission matrices (3D EEMs) revealed that DOM in the estuary was
      primarily from autochthonous origin although terrestrial sources also contributed
      to the DOM production. Parallel factor analysis (PARAFAC) of the EEMs dataset
      indicated that DOM in the estuary was a legacy from the upstream wastewater
      discharging activities, and estuarine mixing was the primary mechanism
      responsible for the decreasing concentrations of DOM components. However, non
      conservative behavior of DOM components was also observed along the center
      transect as a result of additional removal process and spatial heterogeneity in
      the distribution of DOM. Seasonal influence on the concentrations and
      compositions of colloidal DOM in the estuary was also found. Asymmetric flow
      field-flow fractionation (AF4) analysis showed distinct distribution patterns of
      the colloidal DOM during the dry and wet seasons. Behavior of colloidal DOM was
      size-independent and the distribution of colloidal DOM was controlled by multiple
      depletion and replenishment cycles in the dry season, in contrast to those
      observed in the wet season. By combining both EEMs-PARAFAC modeling and AF4
      technique, this study provided important information on the sources and fate of
      bulk and colloidal DOM in a large estuary with intensive anthropogenic
      influences.

PMID- 30293037
TI  - Enhanced bisphenol A removal from stormwater in biochar-amended biofilters:
      Combined with batch sorption and fixed-bed column studies.
AB  - A high-efficient, low-cost, and practical biochar implementation method is
      desired to extend biochar's powerful adsorption performance for environmental
      remediation. This study presents novel results with advanced biochar application
      by integrating biochar with biofilter for the removal of bisphenol A (BPA) from
      stormwater. Biochars derived from wood dust (BC0) at different pyrolytic
      temperatures (300, 500, and 700  degrees C, referred as, BC300, BC500, and BC700,
      respectively) were characterized and investigated for their adsorption of BPA
      under different pH levels and humic acid (HA) concentrations by batch sorption
      and fixed-bed column experiments. Microcosm biofilters vegetated with phragmites
      australis and amended with different biochars were constructed and used for BPA
      removal under different hydraulic loading rates (HLRs). Compared with other
      biochars, BC700 showed a high adsorption rate and capacity due to high specific
      surface area and pore volume. As a consequence, fixed-bed columns amended with
      BC700 can remove BPA more efficiently than columns with BC0, BC300, and BC500
      from synthetic stormwater, though the treatment performance was affected
      relatively by pH change and HA concentration. A high correlation (r2 = 0.899)
      between the breakthrough time and the product of adsorption rate (k2) and
      capacity (Qmax) was found, which suggests that batch sorption experiments could
      be an efficient tool for prediction of breakthrough time. The BPA removal
      efficiency of microcosm biofilters amended with BC0, BC300, BC500 and BC700 for
      real stormwater containing 200 MUg/L BPA at HLR of 40 cm/h averaged 4.1, 10.8,
      80.3, and 98.4%, which were about 6, 15, 115, and 141 times, respectively,
      compared to bilfitlers without biochar amendment. Moreover, biochar amendment not
      only enhanced the BPA removal but also promoted phragmites australis growth,
      elevated nutrients and increased the E. coli removal efficiency. Hence, biochar
      amended biofilters could be a promising approach for enhancing the elimination of
      endocrine-disrupting chemicals such as BPA from aqueous environments.

PMID- 30293038
TI  - DEHP toxicity on vision, neuromuscular junction, and courtship behaviors of
      Drosophila.
AB  - Bis(2-ethylhexyl) phthalate (DEHP) is the most common plasticizer. Previous
      studies have shown DEHP treatment accelerates neurological degeneration,
      suggesting that DEHP may impact retinal sensitivity to light, neurotransmission,
      and copulation behaviors. Although its neurotoxicity and antifertility properties
      have been studied, whether DEHP exposure disrupts vision and how DEHP influences
      neuromuscular junction (NMJ) have not been reported yet. Moreover, the impact of
      DEHP on insect courtship behavior is still elusive. Fruit flies (Drosophila
      melanogaster) were treated with series concentrations of DEHP and observed for
      lifespan, motor function, electroretinogram (ERG), electrophysiology of
      neuromuscular junction (NMJ), courtship behaviors, and relevant gene expression.
      Our results confirmed the DEHP toxicity on lifespan and capacity of motor
      function and updated its effect on copulation behaviors. Additionally, we report
      for the first time that DEHP exposure may harm vision by affecting the synaptic
      signaling between the photoreceptor and the laminar neurons. Further, DEHP
      treatment altered both spontaneous and evoked neurotransmission properties.
      Noteworthy, the effect of DEHP exposure on the copulation behavior is sex
      dependent, and we proposed potential mechanisms for future investigation.

PMID- 30293039
TI  - Contamination, health risk, mineralogical and morphological status of street
      dusts- case study: Erbil metropolis, Kurdistan Region-Iraq.
AB  - Street dusts contamination by heavy metals (HMs) and polycyclic aromatic
      hydrocarbons (PAHs), their mineralogical and morphological properties were
      investigated in Erbil metropolis. A total of 43 soil and street dust samples were
      collected and analyzed, and SPSS, ImageJ, X-powder and positive matrix
      factorization (PMF) software were used for data analyzing. Results showed the
      role of geology in mineralogical status of dusts. Based on ImageJ software
      processing, dust particles with diameters below 10 MUm and low circularity and
      roundness were dominant. The enrichments for Hg, Cu, Pb and Zn contents were
      observed in compare with their calculated local geochemical baselines and
      geoaccumulation index, while, Ni, Co and Cr were categorized as particularly
      unpolluted. However, Hg, Cu and Pb showed the highest ecological risk (Eji)
      values among the studied elements, and 25.80%, 25.80% and 12.90% of the samples
      were classified as very high, moderate and considerable potential ecological
      risks, respectively. Hazard index (HI) followed the decreasing order of Pb > Cr >
      Cu > Ni > Hg > Zn > Co, and ingestion was the main exposure route particularly
      for children. The concentrations of individual PAHs ranged from 1.06 to 1000
      ng/g, with the dominance of 3 and 4-ring compounds. Also, non-carcinogenic PAHs
      concentrations were higher than carcinogenic compounds and toxic equivalents
      (TEQs) ranged from 22.30 to 246.92 ng/g, with a max value in Northern industrial
      zone. Finally, source identification using multivariate statistics and PMF
      introduced three main PAHs and HMs sources in the study area including geogenic,
      traffic and industries, and incinerators (mainly for medical wastes).

PMID- 30293040
TI  - Primary biogenic and anthropogenic sources of organic aerosols in Beijing, China:
      Insights from saccharides and n-alkanes.
AB  - Sugars and n-alkanes are important organic constituents of atmospheric fine
      particulate matter (PM2.5). For better understanding their sources and seasonal
      variations in urban atmosphere, sugar compounds (anhydrosugars, sugars and sugar
      alcohols) and homologue n-alkanes (C18-C37) were studied in PM2.5 samples
      collected from September 2013 to July 2014 in Beijing, China. In general, all
      measured compounds showed the lowest levels in summer. Higher concentrations of
      sugar compounds and n-alkanes were observed in winter, probably due to elevated
      combustion emissions (e.g., coal, biofuel and agricultural residue burning) and
      stable meteorological conditions during heating season. Levoglucosan was the
      major sugar species in all seasons particularly in autumn and winter,
      highlighting the significant contribution of biomass burning to fine organic
      aerosols throughout the whole year especially in cold seasons. Plant waxes
      contributed to n-alkanes the most in late spring (54.5%) and the least in winter
      (11.6%); while fossil fuel combustion had the largest contribution in winter (385
      ng m-3). The weak odd-carbon predominance of n-alkanes in wintertime aerosols
      also suggests fossil fuel combustion as the important source of organic aerosols
      in the heating season. Soil resuspension, fossil fuel combustion and biomass
      burning, and secondary sources are the main sources of OC in PM2.5 at Beijing.
      The seasonal variation in source contributions indicates that meteorological
      condition is a key factor in controlling PM2.5 levels. Furthermore, dust storms
      in spring can strongly enhance the atmospheric level of fine organic matter in
      Beijing.

PMID- 30293041
TI  - Laying performance, blood profiles, nutrient digestibility and inner organs
      traits of hens fed an insect meal from Hermetia illucens larvae.
AB  - Given probable the increment in the nutritional needs of both humans and animals,
      animal production will have increased dramatically by 2050. Insect meals could be
      an alternative protein source for livestock, and they would also be able to
      reduce the environmental problems related to intensive animal production system.
      The aim of this study was to evaluate productive performance, blood analysis,
      nutrient digestibility, and changes in the internal organs of laying hens fed
      Hermetia illucens larvae meal (HI) at two different levels in substitution (25 or
      50%) of soybean meal (SBM). A total of 162 Hy-line Brown hens (sixteen weeks old)
      were equally divided into three experimental groups and fed isoprotein and
      isoenergetic diets. Egg weight, feed intake, and feed conversion rate were not
      affected by the soybean meal substitution at both inclusion levels of insect
      meal. Egg mass was positively affected by the insect meal diets, as was the lay
      percentage, although only at the lowest inclusion level. Dry matter, organic
      matter, and crude protein digestibility coefficients were lower for the HI50
      diet, probably due to the negative effect of chitin. A reduction in serum
      cholesterol and triglycerides was observed in both insect-meal fed groups, while
      serum globulin level increased only at the highest level of insect meal
      inclusion, and, consequently, the albumin to globulin ratio decreased. Overall, a
      protein replacement of 25% with an insect meal from Hermetia illucens larvae in
      the diet of laying hens seems to be more suitable and closer to the optimal
      level.

PMID- 30293042
TI  - First report on solution processed alpha-Ce2S3 rectangular microrods: An
      efficient energy storage supercapacitive electrode.
AB  - Rectangular shaped alpha-Ce2S3 microrods have been grown with the aid of a
      facile, efficient, low cost and low temperature chemical bath deposition (CBD)
      approach in thin film form. Characterizations of alpha-Ce2S3 have been performed
      through structural, morphological and surface wettability studies. Intermixed
      rectangular microrods with lower contact angle provide a reduction in intrinsic
      resistance and effective ion diffusion path during electrochemical activities
      ensuring maximum utilization of the active electrode species. This leads to
      achieve a remarkable specific capacitance of 726 F/g at 2 mV/s scan rate with the
      excellent electrochemical stability of 93% at 2000 CV cycles. Efficient
      electrochemical findings exhibit excellent scope of alpha-Ce2S3 towards next
      generation energy storage devices.

PMID- 30293043
TI  - Copper-indium-sulfide colloids on quantum dot sensitized TiO2 solar cell: Effects
      of capping with mercapto-acid linker molecules.
AB  - The copper-indium-sulfide (CIS) ternary colloids were synthesized in "green"
      water solvent at room temperature employing mercapto-alkyl carboxylic linker
      molecules such as thioglycolic acid (TGA), thioacetic acid (TAA), 2
      mercaptopropionic acid (2-MPA) and l-cysteine (Cys). The stability of the CIS
      colloids is strongly influenced by the structures of linker molecules, and short
      linker molecules induce strong adsorption of the CIS colloids on the TiO2,
      exhibiting strong visible-light absorption and high photo-conductivities. Effects
      of linker molecules capping CIS colloids on the solar cell performances were
      demonstrated. The solar cell performances for the CIS-TiO2 improve as an increase
      of photo-conductivity of the CIS-TiO2 electrodes. In particular, the CIS(TAA)
      TiO2 photoelectrode employing the shortest linker molecules (TAA) exhibited the
      highest PCE yielding with 6.33% (short-circuit current: 14.0 mA/cm2, open-circuit
      voltage: 0.91 V and fill factor: 48.0%).

PMID- 30293044
TI  - The effect of chelating anions on the retention of Co(II) by gamma-alumina from
      aqueous solutions under the unadjusted pH condition of supported catalyst
      preparation.
AB  - This study analyzes the effect of the addition of acetate, citrate, and
      nitrilotriacetate anions on the retention of Co(II) cations by the gamma-alumina
      surface in view of the preparation of alumina supported cobalt catalysts. The
      emphasis was placed on the way the Co(II) species attach to the solid surface
      when adsorbed from aqueous solutions under the unadjusted pH condition. The
      individual adsorption isotherms onto gamma-Al2O3 support for cobalt and a given
      ligand were determined by following the solution depletion method in single
      solute and bi-solute systems. These adsorption data were supplemented by the
      results of potentiometric titrations. In the case of bi-solute systems, the
      adsorption procedures allowed either co-impregnation of gamma-alumina with
      equimolar solutions of cobalt and ligand salts or pre-impregnation of gamma
      alumina with the ligand anions and the subsequent adsorption of cobalt. Changes
      in the pH of the equilibrium solid-liquid suspension were also monitored along
      the adsorption isotherms. The adsorption of Co(II) onto gamma-Al2O3 in the
      presence of acetate and nitrilotriacetate led to the formation of the type A
      (i.e., solid-metal-ligand) ternary complexes. The use of citrate anions together
      with Co(II) cations was shown to improve the impregnation process through the
      formation of ternary complexes of type B (i.e., solid-ligand-metal). The
      comparison with a system containing tricarballylate anions allowed concluding
      that the presence of the hydroxyl group in the citrate anion enhanced its
      affinity for the alumina surface by contributing to the inner-sphere character of
      its surface-bound complexes.

PMID- 30293045
TI  - Synthesis of NiGa2S4-rGO on nickel foam as advanced electrode for flexible solid
      state supercapacitor with superior energy density.
AB  - Pseudocapacitive electrode materials employed in supercapacitors may bring in
      high energy density (ED) and specific capacitance (Csc), which are critical for
      their practical applications. Accordingly, logical design of advanced electrode
      materials is highly demanded to progress high-performance supercapacitors. Here,
      for the first time, we suggest a straightforward route for the synthesis of
      NiGa2S4-rGO as an advanced cathode material supported on nickel foam (NF) for
      employed in flexible solid-state asymmetric supercapacitors (FSASCs). Due to an
      abundant ratio of active sites and large surface area of the NiGa2S4-rGO advanced
      material, the as-prepared NiGa2S4-rGO/NF electrode illustrates considerable
      electrochemical properties including remarkable specific capacitance (Csc) of
      2124.34 F g-1 with excellent rate capability of 73%, and exceptional durability,
      which are better than NiGa2S4/NF and previously reported transition metal
      sulfides (TMSs). Furthermore, for the first time a pseudocapacitive advanced
      anode material of FeSe2-rGO have been successfully fabricated on a nickel foam
      (NF) substrate by a facile strategy. Element Selenium as the favorable element
      was offered into the Fe for enhancement and adjustment of the anode material
      electrochemical performance. The FeSe2-rGO/NF advanced anode electrode presents
      satisfactory electrochemical properties containing an exceptional specific
      capacitance (Csc) of 432.40 F g-1, significant rate performance of 57.84% and
      superior durability, which are better than FeSe2/NF electrode and previously
      studied Fe-based anode material. Considering the remarkable electrochemical
      performance of the as-prepared pseudocapacitive advanced electrode materials, a
      FSASC based on the NiGa2S4-rGO/NF as the cathode electrode and FeSe2-rGO/NF as
      the anode electrode was assembled. The FSASC device delivers superior Csc of
      341.20 F g-1, outstanding energy density (ED) of 121.31 W h kg-1, remarkable
      cycle stability (only 7.30% damage after 5000 charge/discharge (CD) cycles).

PMID- 30293046
TI  - Understanding heat driven gelation of anionic cellulose nanofibrils: Combining
      saturation transfer difference (STD) NMR, small angle X-ray scattering (SAXS) and
      rheology.
AB  - A novel mechanism of heat-triggered gelation for oxidised cellulose nanofibrils
      (OCNF) is reported. We demonstrate that a synergistic approach combining
      rheology, small-angle X-ray scattering (SAXS) and saturation transfer difference
      NMR (STD NMR) experiments enables a detailed characterisation of gelation at
      different length scales. OCNF dispersions experience an increase in solid-like
      behaviour upon heating as evidenced by rheological studies, associated with
      enhanced interfibrillar interactions measured using SAXS. Interactions result in
      an increased fibrillar overlap and increased population of confined water
      molecules monitored by STD NMR. In comparison, cationic cellulose nanofibrils
      (produced by reaction of cellulose with trimethylglycidylammonium chloride) were
      found to be heat-unresponsive.

PMID- 30293047
TI  - Iron species supported on a mesoporous zirconium metal-organic framework for
      visible light driven synthesis of quinazolin-4(3H)-ones through one-pot three
      step tandem reaction.
AB  - A bioinspired iron(III)porphyrinic Zr-MOF, PCN-222(Fe), was modified by post
      synthetic cluster metalation with iron(III) chloride, as a cheap, earth-abundant,
      and environmentally friendly metal precursor, towards formation a new
      multifunctional MOF, namely Fe@PCN-222(Fe). The MOF consists of bimetallic (Zr
      oxo-Fe) nodes linked by Fe(III)porphyrin struts. The cluster metalation and pre
      activation treatment of PCN-222(Fe) were performed cooperatively using the FeCl3.
      The respective MOF was characterized through various techniques, such as FT-IR,
      PXRD, ICP-AES, BET surface area, SEM, UV-Vis DRS, TGA/DSC, PL, and XPS analyses.
      The solid showed catalytic activity for one-pot tandem synthesis of quinazolin
      4(3H)-ones from alcohols and 2-aminobenzamide through a three-consecutive-step
      reaction (oxidation-cyclization-oxidation) under visible light irradiation using
      air or oxygen without adding any additive. In addition, its catalytic performance
      was superior to that of the bare PCN-222(Fe) and the corresponding homogeneous
      catalysts. The experiments indicate that the solid MOF acts as both a photoredox
      and Lewis acid catalyst. Hot-filtration and Fe-leaching tests as well as
      reusability experiments confirm that the nominal MOF acts as an efficient
      reusable heterogeneous catalyst for at least three runs without significant
      decrease in its activity. This work demonstrates the potential of using MOFs as
      supports for single-site metal species towards preparation of multifunctional
      MOFs for modern organic transformations combining photocatalysis and catalysis.

PMID- 30293048
TI  - A systematic review of qualitative studies exploring peer learning experiences of
      undergraduate nursing students.
AB  - BACKGROUND: Peer learning experiences have been reported in previous qualitative
      studies, however individual findings could limit practical leverage due to small
      sample size. Thus it is necessary to integrate invaluable findings from various
      qualitative studies to consider appropriateness and acceptability of peer
      learning in professional nurse education. OBJECTIVE: To identify and synthesize
      qualitative evidence of peer learning experiences of undergraduate nursing
      students so as to understand their perceptions on peer learning experiences.
      DESIGN: A qualitative systematic review was conducted in accordance with the
      Enhancing Transparency in Reporting the Synthesis of Qualitative Research
      (ENTREQ) statement. DATA SOURCES: Database searching was conducted on electronic
      databases such as Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), Science Direct, and MEDLINE that published from 2007 to 2017. REVIEW
      METHODS: Qualitative studies were appraised using the Critical Appraisal Skills
      Programme (CASP). Thematic analysis was used to analyse the data using line by
      line coding, organising coding into descriptive themes, and interpreting further
      to generate new insights. RESULTS: Six studies were included in this review. The
      most common themes identified were integrated into two new insights including
      personal development and professional development. CONCLUSION: This review has
      revealed that peer learning experiences contribute to the learning process of
      undergraduate nursing students in preparing them to become professional nurses
      through personal development and professional development.

PMID- 30293049
TI  - Effects of sodium fluoride on the reproductive development of Bombyx mori.
AB  - Bombyx mori was used as a model to evaluate the reproductive toxicity of NaF in
      insects. Significant reduction in cocoon quality, survival rate, fecundity, and
      hatchability were observed upon NaF treatment groups. Fluoride determination
      indicated that F- has a cumulative effect on the gonad of silkworm. High
      performance liquid chromatography revealed that the testosterone content of males
      was decreased in NaF-treated groups, and enzyme-linked immunosorbent assay showed
      that the estradiol content was decreased in NaF-treated females. Ultrastructural
      observation of testicles of silkworm larvae revealed mitochondrial turgescence,
      endoplasmic reticulum destruction, the appearance of vacuoles and lysosomes, and
      apoptosis and necrosis of cells in NaF-treated groups. Altered tail length and
      tail DNA content in Comet assays further confirmed DNA damage in NaF-treated
      larvae. We demonstrated reproductive toxicity of fluoride toward silkworm at
      physiological and biochemical levels, and the results provide a theoretical basis
      for revealing the reproductive toxicity of fluoride in terrestrial insects.

PMID- 30293050
TI  - No regional gray matter volume reduction observed in young Japanese people at
      ultra-high risk for psychosis: A voxel-based morphometry study.
AB  - OBJECTIVES: Structural brain magnetic resonance imaging studies of individuals at
      ultra-high risk (UHR) for psychosis have shown subtle but widespread reductions
      in baseline gray matter volume (GMV) in the frontal, temporal, and limbic regions
      compared with healthy controls (HC). These regions coincide with regions of
      reduced GMV in patients with established psychosis and have led to the
      consideration of structural changes in UHR as a potential biomarker for future
      transition to psychosis. However, most studies have been from Europe, North
      America, and Australia, with few reports from other regions, and two recent
      studies from Asian countries have failed to detect regional GMV reduction in UHR,
      suggesting the need for further analysis of an Asian sample. In this study, we
      investigated GMV reduction in Japanese UHR subjects. RESULTS: The study used
      voxel-based morphometry to compare magnetic resonance imaging brain scans between
      45 UHR individuals recruited by a specialist and 33 HCs. This showed no
      significant GMV reduction in the UHR group compared with the healthy control
      group. This negative result may be attributable to characteristics of Asian
      samples, such as a low prevalence of illicit drug use, or to the heterogeneous
      nature of UHR subjects.

PMID- 30293051
TI  - Gallic acid inhibits the expression of keratin 16 and keratin 17 through Nrf2 in
      psoriasis-like skin disease.
AB  - Gallic acid (GA), a natural small molecule found in Radix Paeoniae Rubra, has a
      variety of favorable biological activities. However, the anti-psoriasis effect of
      GA has never been explored up to now. This study evaluates the protective effect
      of GA on psoriasis-like skin disease both in vitro and in vivo and explores the
      underlying mechanism. The results show that GA significantly decreases the mRNA
      and protein expression of keratin 16 and keratin 17 which are the markers of
      psoriasis. Additionally, GA obviously ameliorates psoriasis area and severity
      index scores and decreases the epidermal hyperplasia of psoriasis-like disease
      mice. The activity of Nrf2 which targets keratin 16 and keratin 17 is
      significantly downregulated by GA. Furthermore, the downregulation of keratin 16
      and keratin 17 induced by GA was abolished by the Nrf2-overexpression in vitro.
      This study initially elucidates the anti-psoriasis effect and mechanism of GA
      which hints that GA would be a potential candidate for the treatment of
      psoriasis.

PMID- 30293052
TI  - Critical thinking in midwifery practice: A conceptual model.

PMID- 30293053
TI  - Educational intervention to improve critical thinking for undergraduate nursing
      students: A randomized clinical trial.
AB  - The objective of this study was to compare the effectiveness of Problem Based
      Learning (PBL) versus PBL associated with the Active Learning Model for Critical
      Thinking (ALMCT) to improve critical thinking (CT) in nursing students in an
      educational intervention on Basic Life Support (BLS). A two-arm randomized,
      single-blinded, parallel clinical trial was carried out with 108 Brazilian
      undergraduate nursing students who participated in a BLS course. PBL + ALMCT was
      used in the control group (CG), and PBL was used in the experimental group (EG).
      Pre- and post-tests were used to evaluate CT dispositions using the California
      Critical Thinking Dispositions Inventory (CCTDI), and CT skills were evaluated
      using the California Critical Thinking Skills Test (CCTST). The results did not
      indicate significant differences between the CG and EG groups for total CCTDI and
      total CCTST scales and for most of their subscales. However, there was a
      significant difference in the EG when the mean scores on the pre- and post-test
      were compared on the CCTDI analyticity subscale (t = 2073; p = 0.043) and on the
      CCTST analysis subscale (t = 2302; p = 0.025). We strongly recommend further
      studies using PBL associated with ALMCT and randomized clinical trials that last
      more than one month.

PMID- 30293054
TI  - Rationale underpinning postgraduate student nurses' choice of research methods
      used for their masters' theses.
AB  - Many nurses in Taiwan use quantitative research for their master's thesis.
      However, qualitative research explores humankind in depth providing a more
      holistic approach relating to nursing. The purpose of this study was to explore
      the rationale postgraduate students used to choose the research methods for their
      masters' theses in Taiwan. A descriptive qualitative research design was used.
      Data were collected through semi-structured interviews of sixteen nursing
      students studying a master's from seven different Universities in Taiwan in 2016.
      Data were analyzed using thematic analysis. Finding revealed three themes (1)
      Students' personal and professional backgrounds; (2) Myths about quantitative
      research; (3) Misperceptions about qualitative research. Nurse educators could
      use these findings as a reference to design post-graduate nursing courses. It is
      essential to provide a balanced educative experience between delivering
      qualitative and quantitative modules to enhance respect of research method,
      knowledge and skills. Further, this could facilitate students' choice in research
      methods when designing their master's theses.

PMID- 30293055
TI  - Nuclear organization and morphology of cholinergic neurons in the brain of the
      rock cavy (Kerodon rupestris) (Wied, 1820).
AB  - The aim of this study was to conduct cytoarchitectonic studies and choline
      acetyltransferase (ChAT) immunohistochemical analysis to delimit the cholinergic
      groups in the encephalon of the rock cavy (Kerodon rupestris), a crepuscular
      Caviidae rodent native to the Brazilian Northeast. Three young adult animals were
      anesthetized and transcardially perfused. The encephala were cut in the coronal
      plane using a cryostat. We obtained 6 series of 30-MUm-thick sections. The
      sections from one series were subjected to Nissl staining. Those from another
      series were subjected to immunohistochemistry for the enzyme ChAT, which is used
      in acetylcholine synthesis, to visualize the different cholinergic neural centers
      of the rock cavy. The slides were analyzed using a light microscope and the
      results were documented by description and digital photomicrographs. ChAT
      immunoreactive neurons were identified in the telencephalon (nucleus accumbens,
      caudate-putamen, globus pallidus, entopeduncular nucleus and ventral globus
      pallidus, olfactory tubercle and islands of Calleja, diagonal band of Broca
      nucleus, nucleus basalis, and medial septal nucleus), diencephalon (ventrolateral
      preoptic, hypothalamic ventrolateral, and medial habenular nuclei), and brainstem
      (parabigeminal, laterodorsal tegmental, and pedunculopontine tegmental nuclei).
      These findings are discussed through both a functional and phylogenetic
      perspective.

PMID- 30293056
TI  - Intermittent voluntary ethanol consumption combined with ethanol vapor exposure
      during adolescence increases drinking and alters other behaviors in adulthood in
      female and male rats.
AB  - Epidemiological studies suggest that binge drinking is prevalent among
      adolescents, and may result in neurobehavioral consequences. Animal models
      provide the experimental control to investigate the consequences of "binge"
      alcohol exposure during this neurodevelopmental epoch. The current study used an
      animal model that combined an intermittent pattern of alcohol vapor exposure with
      voluntary drinking of 20% unsweetened alcohol in adolescent male and female
      Wistar rats (postnatal day [PD] 22-62), in order to test for potential
      differences in behavioral changes, ethanol drinking, and hypocretin/orexin
      (Hcrt/OX) signaling associated with exposure status. Two weeks after
      discontinuation of the alcohol vapor exposure and drinking during adolescence,
      rats were tested in adulthood for anxiety-like behaviors using a modified open
      field conflict task, pre-pulse facilitation of startle response, light/dark box,
      and marble burying test. Adolescent alcohol exposure led to overall decreased
      startle response and increased behavioral arousal in the light/dark chamber
      during adulthood. Additionally, male rats demonstrated more disinhibited behavior
      during the conflict task compared to females, and female rats exhibited more
      rearing behavior during the light/dark test. Rats were also given a 2-bottle
      choice test that resulted in adolescent alcohol-exposed rats drinking
      significantly more alcohol in adulthood. Further, female rats also consumed more
      alcohol in adulthood compared to males. Estrous cycle phase did not account for
      any of the sex differences observed in the behavioral measures. Histological
      results indicated that adolescent alcohol did not alter Hcrt/OX-1 or Hcrt/OX-2
      receptor mRNA expression levels in adult rats compared to control adults.
      However, female rats expressed a higher level of Hcrt/OX-1 and Hcrt/OX-2 receptor
      mRNA in the frontal cortex compared to males. These data suggest that our current
      model of intermittent ethanol exposure in adolescence can modestly affect both
      behavior and future consumption of alcohol and that Hcrt/OX receptor signaling
      differs between males and females.

PMID- 30293057
TI  - UDP-glycosyltransferase family in Haemonchus contortus: Phylogenetic analysis,
      constitutive expression, sex-differences and resistance-related differences.
AB  - UDP-glycosyltransferases (UGT), catalysing conjugation of UDP-activated sugar
      donors to small lipophilic chemicals, are widespread in living organisms from
      bacteria to fungi, plant, or animals. The progress of genome sequencing has
      enabled an assessment of the UGT multigene family in Haemonchus contortus (family
      Trichostrongylidae, Nematoda), a hematophagous gastrointestinal parasite of small
      ruminants. Here we report 32 putative UGT genes divided into 15 UGT families.
      Phylogenetic analysis in comparison with UGTs from Caenorhabditis elegans, a free
      living model nematode, revealed several single member homologues, a lack of the
      dramatic gene expansion seen in C. elegans, but also several families (UGT365,
      UGT366, UGT368) expanded in H. contortus only. The assessment of constitutive UGT
      mRNA expression in H. contortus adults identified significant differences between
      females and males. In addition, we compared the expression of selected UGTs in
      the drug-sensitive ISE strain to two benzimidazole-resistant strains, IRE and WR,
      with different genetic backgrounds. Constitutive expression of UGT368B2 was
      significantly higher in both resistant strains than in the sensitive strain. As
      resistant strains were able to deactivate benzimidazole anthelmintics via
      glycosylation more effectively then the sensitive strain, UGT368B2 enhanced
      constitutive expression might contribute to drug resistance in H. contortus.

PMID- 30293060
TI  - Researching policy impacts.

PMID- 30293058
TI  - Challenges in drug discovery targeting TriTryp diseases with an emphasis on
      leishmaniasis.
AB  - Tritryps diseases are devastating parasitic neglected infections caused by
      Leishmania spp., Trypanosoma cruzi and Trypanosoma brucei subspecies. Together,
      these parasites affect more than 30 million people worldwide and cause high
      mortality and morbidity. Leishmaniasis comprises a complex group of diseases with
      clinical manifestation ranging from cutaneous lesions to systemic visceral
      damage. Antimonials, the first-choice drugs used to treat leishmaniasis, lead to
      high toxicity and carry significant contraindications limiting its use. Drug
      resistant parasite strains are also a matter for increasing concern, especially
      in areas with very limited resources. The current scenario calls for novel and/or
      improvement of existing therapeutics as key research priorities in the field.
      Although several studies have shown advances in drug discovery towards
      leishmaniasis in recent years, key knowledge gaps in drug discovery pipelines
      still need to be addressed. In this review we discuss not only scientific and non
      scientific bottlenecks in drug development, but also the central role of public
      private partnerships for a successful campaign for novel treatment options
      against this devastating disease.

PMID- 30293059
TI  - Polyunsaturated fatty acid elongation and desaturation in activated human T
      cells: ELOVL5 is the key elongase.
AB  - PUFAs are important constituents of membrane glycerophospholipids. However,
      changes in the capacities to incorporate and metabolize PUFAs when cells enter
      the cell cycle have not been thoroughly studied. In this study, differences in
      the incorporation and metabolism of exogenous PUFAs in resting and proliferating
      primary human T-cells and in the Jurkat cell line were measured. Overall,
      proliferating T-cells and Jurkat cells had a greater capacity to incorporate and
      elongate exogenous 18- and 20-carbon PUFAs compared with resting T-cells.
      Proliferating T-cells and Jurkat cells also showed a greater capacity to
      desaturate 18-carbon PUFA substrates. Consistent with these observations, a
      significant increase in the expression of fatty acid desaturase (FADS) 1, FADS2,
      and elongation of very long chain fatty acids protein (ELOVL) 5 was measured in
      proliferating T-cells compared with resting T-cells. No quantifiable ELOVL2 was
      measured. Knockdown of ELOVL5 in T-cells and Jurkat cells significantly affected
      cellular monounsaturated and PUFA profiles and strongly impaired the elongation
      of 18- and 20-carbon PUFAs. In conclusion, the induction of proliferation in
      human T-cells is associated with a significant increase in the capacity to take
      up and metabolize exogenous PUFAs, and ELOVL5 is responsible for the elongation
      of 18- and 20-carbon PUFAs in these cells.

PMID- 30293061
TI  - Parasitoid Jewel Wasp Mounts Multi-Pronged Neurochemical Attack to Hijack a Host
      Brain.
AB  - The parasitoid emerald jewel wasp Ampulex compressa induces a compliant state of
      hypokinesia in its host, the American cockroach Periplaneta americana through
      direct envenomation of the central nervous system (CNS). To elucidate the
      biochemical strategy underlying venom-induced hypokinesia, we subjected the venom
      apparatus and milked venom to RNAseq and proteomics analyses to construct a
      comprehensive "venome", consisting of 264 proteins. Abundant in the venome are
      enzymes endogenous to the host brain, including M13 family metalloproteases,
      phospholipases, adenosine deaminase, hyaluronidase, and neuropeptide precursors.
      The amphipathic, alpha-helical ampulexins are among the most abundant venom
      components. Also prominent are members of the Toll/NF-kappaB signaling pathway,
      including proteases Persephone, Snake, Easter, and the Toll receptor ligand
      Spatzle. We find evidence that venom components are processed following
      envenomation. The acidic (pH~4) venom contains unprocessed neuropeptide
      tachykinin and corazonin precursors and is conspicuously devoid of the
      corresponding processed, biologically active peptides. Neutralization of venom
      leads to appearance of mature tachykinin and corazonin, suggesting that the wasp
      employs precursors as a prolonged time-release strategy within the host brain
      post-envenomation. Injection of fully processed tachykinin into host cephalic
      ganglia elicits short-term hypokinesia. Ion channel modifiers and cytolytic
      toxins are absent in A. compressa venom, which appears to hijack control of the
      host brain by introducing a "storm" of its own neurochemicals. Our findings
      deepen understanding of the chemical warfare underlying host-parasitoid
      interactions and in particular neuromodulatory mechanisms that enable
      manipulation of host behavior to suit the nutritional needs of opportunistic
      parasitoid progeny.

PMID- 30293063
TI  - Special Viral Clearance Issue and St Gallen PDA Collaboration Paper.

PMID- 30293064
TI  - Hemoglobin variants found in relation to HbA1c testing: high occurrence of Hb
      Athens-Georgia in the Northern Jutland, Denmark.

PMID- 30293062
TI  - Improvements to the rice genome annotation through large-scale analysis of RNA
      Seq and proteomics datasets.
AB  - Rice (Oryza sativa) is one of the most important worldwide crops. The genome has
      been available for over 10 years and has undergone several rounds of annotation.
      We created a comprehensive database of transcripts from 29 public RNA sequencing
      datasets, officially predicted genes from Ensembl plants, and common contaminants
      in which to search for protein-level evidence. We re-analysed nine publicly
      accessible rice proteomics datasets. In total, we identified 420K peptide
      spectrum matches from 47K peptides and 8,187 protein groups. 4168 peptides were
      initially classed as putative novel peptides (not matching official genes).
      Following a strict filtration scheme to rule out other possible explanations, we
      discovered 1,584 high confidence novel peptides. The novel peptides were
      clustered into 692 genomic loci where our results suggest annotation
      improvements. 80% of the novel peptides had an ortholog match in the curated
      protein sequence set from at least one other plant species. For the peptides
      clustering in intergenic regions (and thus potentially new genes), 101 loci were
      identified, for which 43 had a high-confidence hit for a protein domain. Our
      results can be displayed as tracks on the Ensembl genome or other browsers
      supporting Track Hubs, to support re-annotation of the rice genome.

PMID- 30293065
TI  - Cholesteryl Ester Transfer Protein Variant (RS1800777) with Liver Histology in
      Non-Alcoholic Fatty Liver Disease Patients.
AB  - INTRODUCTION AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of
      diseases ranging from simple steatosis without inflammation or fibrosis to
      nonalcoholic steatohepatitis and in the Western countries has become one of the
      most prevalent chronic liver diseases related to metabolic and lipid alterations.
      Cholesteryl ester transfer protein (CETP) participates in high density
      lipoprotein (HDL)-cholesterol metabolism. The aim of our study was to investigate
      the influence of polymorphism (rs1800777) of CETP gene on liver histological
      changes, biochemical parameters, and serum adipokines levels in patients with
      NAFLD. MATERIAL AND METHODS: A population of 90 patients with NAFLD was recruited
      in a cross-sectional study. A biochemical analysis (glucose, c-reactive protein,
      insulin, homeostasis model assessment-insulin resistance, total cholesterol, low
      density lipoprotein (LDL)-cholesterol, HDL-cholesterol, triglycerides blood, and
      adipokines (leptin, adiponectin, and resistin) was realized. Genotype of
      polymorphism (rs1800777) of CETP gene was studied. RESULTS: Eighty-three patients
      (92.2%) had the genotype GG (wild type group) and 7 patients (7.8%) had the
      genotype GA (n = 7) or AA (n = 0; mutant type group). Patients with A allele show
      significant decrease in liver biochemistry parameters - Alanine amino transferase
      (delta 10.1 +/- 9.9 UI/L; p = 0.01), aspartate aminotransferase activity (delta
      13.3 +/- 9.5 UI/L; p = 0.02), and gammaglutamine transferase levels (delta 39 +/-
      30.1 UI/L; p = 0.01). Logistic regression analysis indicated that subjects with A
      allele carriers were associated with a decreased risk of lobulillar inflammation
      (OR 0.18, 95% CI 0.04-0.95, p = 0.04) and a decreased risk of steatosis (OR 0.13,
      95% CI 0.02-0.89, p = 0.04). CONCLUSIONS: A variant of the polymorphism rs1800777
      of CETP gene is independently associated with the presence of steatosis and
      lobulillar inflammation in subjects with proven biopsy NAFLD.

PMID- 30293066
TI  - Assessment of Suspected Vascular Rings and Slings and/or Airway Pathologies Using
      Magnetic Resonance Imaging Rather Than Computed Tomography.
AB  - BACKGROUND: Congenital cardiovascular malformations (CCVM) may cause infrequently
      airway pathologies (AP) in children and are of prognostic and therapeutic
      relevance. While computed tomography (CT) is considered first-line imaging
      modality in many centres, we started using magnetic resonance imaging (MRI) more
      and more in the last years to detect CCVM and AP to avoid radiation in this
      patient group. OBJECTIVE: The aim of this retrospective study was to determine
      and to compare the diagnostic accuracy of CT and MRI when used to detect CCVM
      and/or AP. METHODS: All patients suspected to have CCVM and/or AP and examined
      either by CT or MRI between 2000 and 2013 in our hospital were included.
      Extension and type of CCVM, as well as their relationship to esophagus, trachea
      or bronchi were assessed and related to findings of tracheobronchoscopy, cardiac
      catheterization or surgery if available. RESULTS: One hundred six patients
      (median [range] 4 years [2 days to 66 years]) were examined by CT (n = 27) or MRI
      (n = 79). In 78 patients (74%), CCVM and/or AP were found with either of the
      imaging methods. CCVM were found in 63 subjects. Forty-six of 63 subjects had
      both, CCVM and AP. The presence of CCVM was always detected correctly by CT or
      MRI, although both techniques had a weakness detecting atretic segments directly.
      AP (n = 61) were correctly diagnosed in all patients not intubated for artificial
      ventilation by CT (n = 17) and in all but 2 patients by MRI (39 out of 41).
      CONCLUSIONS: MRI is sensitive to detect CCVM associated with AP equally to CT
      without any radiation exposure.

PMID- 30293067
TI  - Effect of Increased Convection Volume by Mid-Dilution Hemodiafiltration on the
      Subclinical Chronic Inflammation in Maintenance Hemodialysis Patients.
AB  - Mid-dilution hemodiafiltration (MID) is a dialytic technique that might improve
      systemic inflammation of patients in chronic hemodialysis (HD) by increasing
      substitution volumes. To verify this hypothesis, we performed a prospective cross
      over study comparing the effect on inflammatory biomarkers of higher convection
      by MID versus standard convection by post-dilution hemodiafiltration (HDF).
      Patients under chronic HD were therefore treated by MID and HDF by crossover
      design. Each treatment period lasted 4 months, with 1 month of wash-out where
      patients were treated by HD, for a total of 9 months. Primary outcome was the
      change of serum pre-dialytic C-Reactive Protein (CRP), interleukin 6 (IL-6), IL
      1, IL-10, transforming growth factor-beta (TGF-beta), tumor necrosis factor
      alpha, albumin and pre-albumin. Samples were obtained monthly. Ten HD patients
      were enrolled (age: 64.9 +/- 12.6 years; 70% males; dialytic vintage: 10.6 [2.7
      16.2] years). Mean convection volume was 40.1 +/- 2.5 L/session in MID and 20.1
      +/- 2.6 L/session in HDF. A significant reduction of beta2-Microglobulin was
      detected as a result of either treatment. In MID, CRP decreased from 11.3 (3.2
      31.0) to 3.1 (1.4-14.4) mg/L (p = 0.007), IL-6 from 12.7 (5.0-29.7) to 8.3 (4.4
      14.0) pg/mL (p = 0.003), and TGF-beta from 10.6 (7.4-15.6) to 7.4 (5.9-9.3) ng/mL
      (p = 0.001). A significant reduction of CRP from 8.5 (3.2-31.0) to 4.6 (3.2-31.0)
      mg/L was also detected in HDF (p = 0.037), whereas no significant reduction of IL
      6 (p = 0.147) and TGF-beta (p = 0.094) was found. Percentage reduction of IL-6
      correlated with mean convective volume in HDF (R = 0.666; p = 0.036) and in MID
      (R = 0.760; p = 0.020). Therefore, MID and HDF are associated with an attenuation
      of inflammatory pattern that is correlated with a high convective volume.

PMID- 30293068
TI  - Relation of the Ankle Brachial Index to Left Ventricular Ejection Fraction in
      Patients Without Coronary Artery Disease.
AB  - BACKGROUND: The low ankle brachial index (ABI) values are indicative of
      peripheral arterial disease, but have recently been found to be associated with
      reduced left ventricular ejection fraction (LVEF). This may relate to coexisting
      coronary artery disease (CAD). AIM: This study prospectively assessed a potential
      ABI-LVEF association in patients without CAD. METHODS AND RESULTS: We studied 55
      patients (age 57 +/- 13 years, 49% male) with normal coronary arteries with LVEF
      determination. ABI, pulse wave velocity (PWV), and augmentation index (AI) were
      performed after coronary angiography. ABI correlated with LVEF (r = 0.40, p =
      0.002), but not with PWV or AI. On linear regression analysis, ABI was
      independently associated with LVEF (B = 0.42, p = 0.004). The median LVEF was
      lower in subjects with low ABI values compared to those with normal ABI values
      (33 vs. 61%; p = 0.001). CONCLUSION: ABI may be influenced by LVEF independently
      of CAD, arterial stiffness or pressure wave reflection.

PMID- 30293069
TI  - Abstracts 18th ESASO Retina Academy.

PMID- 30293070
TI  - Title Page/ Table of Contents.

PMID- 30293071
TI  - Exercise Training After Pulmonary Endarterectomy for Patients with Chronic
      Thromboembolic Pulmonary Hypertension.
AB  - BACKGROUND: After undergoing a procedure of pulmonary endarterectomy (PEA),
      patients with chronic thromboembolic pulmonary hypertension (CTEPH) may still
      experience reduced exercise capacity. Data on effects of exercise training in
      these patients are scant. OBJECTIVES: To evaluate the effectiveness of exercise
      training after PEA for CTEPH and if the presence of "residual pulmonary
      hypertension" may affect the outcome. METHODS: Retrospective data analysis of
      CTEPH patients undergoing inpatient exercise training after PEA. According to
      predefined criteria, patients were divided into those with (group 1) and without
      (group 2) a "good" post-surgery hemodynamic response. Assessments of the 6-min
      walking distance test (6-min walking distance test [6 MWT]: primary outcome) were
      performed before and after surgery (before training), after training and at 3
      month follow-up. Hemodynamic and lung function data were also analyzed. RESULTS:
      Data of 84 and 26 patients of groups 1 and 2, respectively, were analyzed. After
      surgery patients showed a reduction in 6 MWT, which significantly reversed after
      training and further improved at 3 months (p = 0.0001), without any significant
      difference between groups. The percentage of patients reaching the minimal
      clinically important difference in 6 MWT was similar between groups. The
      sig<X00_Del_TrennDivis>-</X00_Del_TrennDivis>nificant (p = 0.0001) post-surgery
      improvement in hemodynamics was maintained at 3 months without any significant
      difference between groups. New York Heart Association functional class improved
      in parallel to the hemodynamic improvement. CONCLUSIONS: Exercise training in
      patients with CTEPH after PEA, an inpatient exercise training program, improves
      exercise capacity for up to 3 months, independently of the post-surgery
      hemodynamic response.

PMID- 30293072
TI  - Clinical and Sonographic Model to Predict Cesarean Delivery after Induction of
      Labor at Term.
AB  - OBJECTIVE: To develop a model combining clinical and sonographic features to
      predict the risk of cesarean delivery after the induction of labor (IOL).
      METHODS: We designed a prospective observational study involving women admitted
      for IOL. The main outcome was defined as cesarean delivery due to failed IOL or
      arrest of labor. Several clinical and ultrasonographic variables were collected.
      Seventy percent of the sample was used to build the predictive model, using
      stepwise logistic regression, while the remaining sample was used for validation.
      The final model was estimated and calibrated using all participants. RESULTS: We
      analyzed 477 pregnancies. The main outcome occurred in 102/477 (21.4%) women. The
      final model included previous vaginal delivery (odds ratio [OR] 0.088; 95%
      confidence interval [CI] 0.04-0.21), height (OR 0.904; 95% CI 0.87-0.94), body
      mass index before delivery (OR 1.084; 95% CI 1.02-1.15), ultrasonographic
      estimated fetal weight (OR 3.965; 95% CI 2.18-7.22), and ultrasonographic
      cervical length (OR 1.065; 95% CI 1.04-1.09) as predictors. Area under the
      receiver operating characteristics curve was 0.826 (95% CI 0.78-0.87). For a 5%
      false-positive rate, the sensitivity, specificity, and positive and negative
      likelihood ratios were 44.1%, 94.9%, 8.7, and 0.59, respectively. CONCLUSION: Our
      model combining clinical and ultrasonographic features might offer individualized
      counseling regarding risk of cesarean delivery to women who are candidates for
      IOL.

PMID- 30293073
TI  - Success Rates for Retinal Detachment Repair in Alberta: A Physician Learning
      Program Initiative.
AB  - OBJECTIVE: To identify primary surgical success rates for retinal detachment
      repair in Alberta and compare functional outcomes of methods of repair. METHODS:
      Data was retrospectively extracted from the Alberta Health Services Discharge
      Abstract Database and the National Ambulatory Care Reporting System for all
      patients diagnosed with retinal detachment and vitreoretinal procedures during
      the 2008/09 to 2012/13 fiscal years. RESULTS: Of the 5,433 surgeries for retinal
      detachment identified, 279 were excluded due to invalid provincial health
      numbers, unidentified procedure location, and/or treating physician other than an
      Alberta retina surgeon. The final analysis included 4,336 detachments in 4,020
      patients. The average primary retinal detachment success rate was 84.9%
      (3,680/4,336). Primary success rates varied between vitrectomy only (84.9%,
      2,149/2,532), vitrectomy and scleral buckle (85.5%, 818/957), and scleral buckle
      (84.4%, 702/832). CONCLUSIONS: Alberta retina surgeons have an average primary
      success rate of 84.9% (3,680/4,336) for repair of retinal detachments. This
      result is in keeping with other published retinal detachment success rate
      studies.

PMID- 30293074
TI  - Health-Related Quality of Life in Patients with Small Intestine Neuroendocrine
      Tumours.
AB  - BACKGROUND: The prevalence of small intestine neuroendocrine tumours (SI-NETs) is
      increasing. Disease progression is often slow and treatment options and long-term
      survival rates have improved, but little is known about health-related quality of
      life (HRQoL) in these patients. <br>Objective: To assess HRQoL and its predictors
      in SI-NET patients receiving contemporary treatments. <br>Methods: We measured
      HRQoL with 15D and SF-36 questionnaires in 134 SI-NET patients and compared the
      15D results to those of age- and gender-standardized general population (n =
      1153). In the patients, we studied impact of treatments, Ki67, liver metastases,
      circulating tumour markers, comorbidities and/or socioeconomic factors on HRQoL
      with linear regression analysis. <br>Results: Mean disease duration of the
      patients was 81 (4-468) months, 91% had metastatic disease and 79% received
      somatostatin analog treatment. Hepatic tumour load was 0% in 44.8%, <10-25% in
      44.0%, and >25% in 11.2%, respectively. Mean fP-CgA and S-5HIAA concentrations
      were 15 (1.3-250) nmol/l and 344 (24-7470) nmol/l, respectively. Overall HRQoL
      was significantly impaired in patients compared to controls (15D scores 0.864+/
      0.105 vs 0.905+/-0.028, p<0.001). SI-NET patients scored worse on 9 of 15
      dimensions (sleep, excretion (ie bladder and bowel function), depression,
      distress, vitality, sexual activity (p< 0.001), breathing, usual activities, and
      discomfort and symptoms (p< 0.01-0.05). SF-36 scores were impaired and highly
      correlated with 15D scores (p<0.001). HRQoL was impaired in patients with (n=85)
      compared to patients without (n=49) impaired excretion (0.828 vs 0.933, p<0.001).
      In the patient group, number of medications predicted impaired HRQoL.
      <br>Conclusions: Despite contemporary treatments, SI-NET patients have severely
      impaired HRQoL, including diarrhea, sleep, depression, vitality and sexual
      activity. <br>.

PMID- 30293075
TI  - Different Chemotherapy Regimens in the Management of Advanced or Metastatic
      Urothelial Cancer: a Bayesian Network Meta-Analysis of Randomized Controlled
      Trials.
AB  - BACKGROUND/AIMS: Urothelial cancer (UC) as a chemotherapy-sensitive tumor, has
      achieved remarkable progresses in therapeutic paradigm, particularly in the
      advanced/metastatic stages. However, both clinicians and patients are confused
      when it comes to choosing the optimal chemotherapy. Hence, this article was aimed
      to conduct a comprehensive comparison of different chemotherapy regimens for
      advanced or metastatic UC in terms of survival benefits or adverse events.
      METHODS: The online databases PubMed, EMBASE and Web of Science were searched
      systematically and comprehensively for randomized controlled trials (RCTs) up to
      September 15, 2017. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95%
      credible interval (CrI) were calculated by Markov chain Monte Carlo methods. The
      effectiveness and safety of included regimens were conducted to provide a
      hierarchy by means of rank probabilities with the help of "R-3.4.0" software and
      the "gemtc-0.8.2" package. The surface under the cumulative ranking curve (SUCRA)
      was also incorporated in our analysis for ranking the corresponding chemotherapy
      regimens. RESULTS: Ten different chemotherapy regimens involved in this article
      were predominantly of trials in a first-line setting, and eight clinical outcomes
      were ultimately analyzed in this study. In terms of Overall response rate (ORR),
      Overall survival (OS) or Progression-free survival (PFS)/Time to progression
      (TTP), the rank probabilities and SUCRA indicated that
      Paclitaxel/cisplatin/gemcitabine (PCG) was superior to gemcitabine/cisplatin (GC)
      or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), the traditional first
      line treatment for advanced/metastatic UC. In the case of ORR or PFS/TTP,
      GC+sorafenib also displayed its superiority in comparison with GC or MVAC.
      Despite their survival benefits, PCG or GC+sorafenib presented a relatively
      higher incidence of adverse events. CONCLUSION: Our results revealed that by
      adding a paclitaxel or sorafenib into the first-line GC, it could yield a better
      survival benefit, but also worsen adverse events for advanced/ metastatic UC.
      Clinically, physicians should weigh the merits of these approaches to maximize
      the survival benefits of eligible patients.

PMID- 30293076
TI  - Surfactant Proteins A and D: Trimerized Innate Immunity Proteins with an Affinity
      for Viral Fusion Proteins.
AB  - Innate recognition of viruses is an essential part of the immune response to
      viral pathogens. This is integral to the maintenance of healthy lungs, which are
      free from infection and efficient at gaseous exchange. An important component of
      innate immunity for identifying viruses is the family of C-type collagen
      containing lectins, also known as collectins. These secreted, soluble proteins
      are pattern recognition receptors (PRRs) which recognise pathogen-associated
      molecular patterns (PAMPs), including viral glycoproteins. These innate immune
      proteins are composed of trimerized units which oligomerise into higher-order
      structures and facilitate the clearance of viral pathogens through multiple
      mechanisms. Similarly, many viral surface proteins form trimeric configurations,
      despite not showing primary protein sequence similarities across the virus
      classes and families to which they belong. In this review, we discuss the role of
      the lung collectins, i.e., surfactant proteins A and D (SP-A and SP-D) in viral
      recognition. We focus particularly on the structural similarity and
      complementarity of these trimeric collectins with the trimeric viral fusion
      proteins with which, we hypothesise, they have elegantly co-evolved. Recombinant
      versions of these innate immune proteins may have therapeutic potential in a
      range of infectious and inflammatory lung diseases including anti-viral
      therapeutics.

PMID- 30293077
TI  - Difference in Stroke Knowledge between Rural and Urban Communities in a
      Developing Country after Community-Based Stroke Educational Campaigns: Results
      from a Cross-Sectional Study.
AB  - BACKGROUND: Ischemic stroke is a leading cause of disability and death in Mexico.
      Poor ability to identify signs and symptoms of ischemic stroke leads to longer
      hospital arrival times and precludes prompt treatment. The knowledge of stroke
      risk factors and warning signs in rural population is scarce. Since 2010, Stroke
      Education Campaigns are performed with a community-based approach. The aim of
      this study was to assess and compare stroke knowledge in rural and urban
      communities. METHODS: During World Stroke Campaign, a standardized questionnaire
      to assess knowledge of stroke risk factors and warning signs was applied in urban
      and non-urban communities of Nuevo Leon, Mexico. RESULTS: A total of 4,144
      surveys were collected. Mean age was 44.2 +/- 16.1 and 75.9% were women. People
      from rural and semi-urban areas mentioned > 3 risk factors (p < 0.001) and
      warning signs (p < 0.001) compared to the urban area. After logistic regression
      analysis, having received previous information about stroke remained significant
      for the knowledge of > 3 stroke risk factors and warning signs (p < 0.001; 95% CI
      1.997-2.727; p < 0.001; 95% CI 1.880-3.787) respectively. CONCLUSIONS: Rural and
      semi-urban regions performed better than the urban population. Receiving stroke
      information is a determinant factor for stroke knowledge. Stroke Educational
      Campaigns are a cost-effective method for raising stroke awareness, thus reducing
      stroke burden.

PMID- 30293078
TI  - Functional Outcome and Quality of Life after Ileal Pouch-Anal Anastomosis within
      a Defined Population in Sweden.
AB  - OBJECTIVE: The purpose of this population-based study was to present
      prospectively recorded functional data and health-related quality of life (HRQOL)
      questionnaire data to assess the long-term results of the first 100 consecutive
      ileal pouch-anal anastomosis (IPAA) performed chronologically by 3 surgeons in a
      single referral centre. METHODS: During 1993-2008, 100 patients underwent IPAA.
      The 90 patients still alive with an intact pouch were included (response rate =
      92%). Function was evaluated using St Mark's incontinence score, and HRQOL with
      SF-36. RESULTS: At 18 months after loop ileostomy closure, 63 patients (76%) had
      4-6 day-time and 47 patients (57%) had no night-time bowel movements. A stapled
      IPAA resulted in better St Mark's (p = 0.0064) and Wexner scores (p = 0.0019)
      than did a hand-sewn anastomosis. The younger the patients were at the onset of
      ulcerative colitis (UC) the better St Mark's (p = 0.0037) and Wexner scores (p =
      0.011) were. The patients scored significantly higher than did the general
      Swedish population adjusted by age-group and sex in 6 out of 7 SF-36 subscales.
      CONCLUSIONS: In the hands of experienced high-volume surgeons, IPAA is a safe
      procedure associated with good functional results that are stable over time.
      Stapled IPAA and younger age at onset of UC were correlated with better
      functional results. The HRQOL scores were high.

PMID- 30293079
TI  - Investigation of Therapeutic Effects of Erdosteine on Polycystic Ovary Syndrome
      in a Rat Model.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is a serious endocrine disorder. In
      the present study, we investigated the therapeutic effects of erdosteine in
      letrozole induced-PCOS in rats. <br><br>Methods: Thirty two wistar albino female
      rats were grouped as control group (C), PCOS group (PCOS), PCOS-metformin group
      (PCOS+MET), PCOS-erdosteine group (PCOS+Erd). Polycystic ovary syndrome was
      induced by administering letrozole; such rats presented with sex hormone
      disorder, abnormal estrous cycles determined by daily vaginal smear, large cystic
      follicles, and increasing fasting insulin levels. After induction of PCOS,
      Metformin (500 mg/kg/day) and Erdostein (100 mg/kg/day) were given orally to the
      treatment groups for 30 days. Serum concentrations of glucose, total cholesterol,
      low- and high-density lipoprotein, triglyceride, as well as the total oxidant and
      antioxidant status, oxidative stress index, circulating estrone (E1), estradiol
      (E2), testosterone, androstenedione were evaluated. The ovaries were graded
      histologically. RESULTS: Weights of ovarian tissues (p < 0.05) and the number of
      atretic follicles (p < 0.001) and cystic follicles (p < 0.01) decreased in
      PCOS+Erd group; the corpus luteum number was significantly higher in PCOS+Erd
      group (p < 0.01) as compared with PCOS group. Lipid parameters (Total-C, LDL-C
      and TG), E1 (Estrone), E1/E2 ratio, testosterone and androstenedione
      significantly decreased, while HDL-C, E2 (Estradiol) significantly increased in
      PCOS+Erd group as compared with PCOS group. Moreover glucose, insulin and HOMA-IR
      were reduced with treatment of Erdosteine (p > 0.05, p < 0.001, p < 0.001
      respectively). CONCLUSION: It is suggested that Erdosteine may be used in
      treatment of PCOS as an alternative to metformin. It appears that our findings
      might be supported by clinical and molecular studies. <br><br>.

PMID- 30293080
TI  - Epirubicin is More Effective than Miriplatin in Balloon-Occluded Transcatheter
      Arterial Chemoembolization for Hepatocellular Carcinoma.
AB  - BACKGROUND: Transcatheter arterial chemoembolization (TACE) is a standard therapy
      used in the treatment of intermediate hepatocellular carcinoma (HCC). Recently,
      balloon-occluded TACE (B-TACE) has been developed. PURPOSE: This study aimed to
      clarify the effects of B-TACE in patients with HCC, with a focus on which drug is
      suitable to suspend in Lipiodol for B-TACE. METHODS: We retrospectively evaluated
      35 patients with HCC treated with B-TACE. Factors associated with enhanced time
      to progression (TTP) after B-TACE were evaluated using univariate and
      multivariate analyses. RESULTS: A total of 35 patients with HCC (40 nodules) were
      treated with B-TACE between June 2013 and August 2016. Epirubicin was used in 25
      nodules and miriplatin was used in 15 nodules. Epirubicin (15.1 months) was
      significantly better than miriplatin (3.2 months) in prolonging the local TTP
      after B-TACE (p = 0.0293). Epirubicin showed a positive tendency in TE4 (100%
      tumor necrosis) rate when compared with miriplatin (p = 0.058). Achievement of
      TE4 was the only significant factor associated with better TTP after B-TACE.
      Epirubicin- and TACE-naive statuses were significant factors in achieving TE4
      with B-TACE. CONCLUSION: To enhance the TTP with B-TACE, TE4 should be achieved.
      Epirubicin is a more optimal anticancer drug (as a Lipiodol suspension) than
      miriplatin for achieving TE4 with B-TACE.

PMID- 30293081
TI  - High-Salt Diet Gets Involved in Gastrointestinal Diseases through the Reshaping
      of Gastroenterological Milieu.
AB  - BACKGROUND: Gastrointestinal (GI) diseases are known to be largely influenced by
      one's lifestyle and dietary uptake. A high-salt diet (HSD) is well recognized as
      a risk factor for cardiovascular complications, hypertension, and metabolic
      syndromes. However, the relationship between an HSD and the GI system, which is
      the compartment that comes in direct contact with exogenous stimulants, has not
      been fully explored. AIMS: We seek to better understand the complexity of the
      pathogenic effects of an HSD in the context of GI disorders. METHODS: By
      searching the PubMed and Web of science, the review of literature was performed
      using keywords: high-salt and GI, high-salt and immunity, salt and microbiota,
      salt and hormone. RESULTS: In this review, we concluded that high-salt intake
      potentially perturbs the local immune homeostasis, alters the gut microbiota
      composition and function, and affects the endocrine hormone profiling in the GI
      system. CONCLUSION: HSD might get involved in GI diseases through the reshaping
      of gastroenterological milieu, which could help to better understand the
      complexity of the pathogenic effects of an HSD in the context of GI disorders.

PMID- 30293082
TI  - The Effect of Autoantibody against M2-Muscarinic Acetylcholine Receptor in Heart
      Failure Patients on Digoxin Treatment.
AB  - BACKGROUND: Autoantibody against M2-muscarinic acetylcholine receptor (anti
      M2AChR) has a biological effect similar to a vagus agonist. Digoxin has a
      function of vagus nervous system stimulation. We hypothesized that anti-M2AChR is
      highly correlated with digoxin in patients with chronic heart failure (CHF).
      METHODS: Synthetic M2AChR peptides served as the target antigen in an ELISA were
      used to screen the sera of 80 CHF patients, who were separated into a negative (
      ) or positive (+) anti-M2AChR group according to their anti-M2AChR reactivity.
      Echocardiography and serum digoxin concentration (SDC) were performed at baseline
      and after 1 year of digoxin in combination with the standard treatment regime.
      The end-point events were compared over 1 year of follow-up. RESULTS: Seventy-two
      CHF patients completed the final data analysis, including 32 (+)anti-M2AChR and
      40 (-)anti-M2AChR patients. The resting heart rate of the positive group was
      higher than that of the negative group at baseline (p < 0.05; 89.0 +/- 1.6 vs.
      83.8 +/- 1.1 bpm). Both groups showed improvement in the left ventricular end
      diastolic and end-systolic dimensions and ejection fraction with digoxin in
      combination with the standard treatment regime for 1 year (all p < 0.01).
      However, the 32 patients with (-)anti-M2AChR had greater improvements than the 40
      patients with (+)anti-M2AChR, and this was accompanied by a marked decrease of
      rehospitalization (all p < 0.01) but not of cardiovascular mortality after 1
      year. The SDC of patients with (-)anti-M2AChR was significantly lower than that
      of patients with (+)anti-M2AChR (p < 0.05; 0.63 +/- 0.05 vs.1.16 +/- 0.06 ng/mL)
      and had a positive correlation with anti-M2AChR (r = 0.81, p < 0.001).
      CONCLUSION: These results suggested that anti-M2AChR could be a useful biomarker
      of vagus nerve overactivation and is associated with a poor response to digoxin
      treatment in CHF patients.

PMID- 30293083
TI  - Gambogic Acid Induces Apoptosis of Non-Small Cell Lung Cancer (NSCLC) Cells by
      Suppressing Notch Signaling.
AB  - BACKGROUND Activation of Notch signaling was found to be associated with cancer.
      Gambogic acid (GA) was reported to be an anti-cancer agent. This study
      investigated the anti-cancer effect of GA on human non-small cell lung cancer
      (NSCLC) cells. Involvement of the Notch pathway was also studied. MATERIAL AND
      METHODS GA at 0, 0.5, 0.75, and 1.0 MUmol/l was used to incubate A549 and SPC-A1
      cells. MTT assay was used to determine the cell viability. TUNEL assay was used
      to detect the apoptosis. Western blotting was used to evaluate protein expression
      levels, protein phosphorylation levels, and nuclear translocation levels. RESULTS
      Notch signaling pathway was activated in NSCLC cells. GA treatment significantly
      inhibited NSCLC cell viability and increased cell apoptosis. GA treatment
      significantly decreased the expression levels of DLL1, DLL3, DLL4, Jagged1,
      Jagged2, Bcl2, and PK3K, inhibited NICD nuclear translocation and Akt
      phosphorylation, and increased expression level of active caspase3. CONCLUSIONS
      GA inhibited NSCLC cell viability by inducing apoptosis. Inhibition of the Notch
      signaling pathway was the mechanism involved in the anti-proliferation effect of
      GA on NSCLC.

PMID- 30293084
TI  - Toll-Like Receptor 4 (TLR-4) Pathway Promotes Pulmonary Inflammation in Chronic
      Intermittent Hypoxia-Induced Obstructive Sleep Apnea.
AB  - BACKGROUND Studies have shown that intermittent hypoxia mimics obstructive sleep
      apnea in causing pulmonary inflammation, but the mechanism is not yet clear.TLR-4
      is a recognized proinflammatory factor, so the purpose of this study was to
      assess the function of TLR-4 in pulmonary inflammation induced by chronic
      intermittent hypoxia simulating obstructive sleep apnea. MATERIAL AND METHODS
      Healthy male Wistar rats were divided into 3 groups (8 in each group): the
      normoxia control group (CG), the intermittent hypoxia group (IH), and the TLR4
      antagonist TAK242 treatment group (3 mg/kg, daily), with exposure durations of 12
      weeks and 16 weeks (HI). The morphological changes of lung tissue were determined
      with hematoxylin-eosin (HE) staining. The expressions of the TLR-4 pathway in
      lung tissue were tested by Western blotting and RT-PCR. The levels of IL-6 and
      TNF-a in serum and lung tissue were detected by enzyme-linked immunosorbent assay
      (ELISA). The levels of SOD and MDA in lung tissue were detected by use of SOD and
      MDA kits, respectively. RESULTS After TAK242 treatment, damage to lung tissue was
      increased, and the expressions of TLR-4, MYD88, P65, IL-6, TNF-alpha, MDA, and
      SOD were decreased. Intermittent hypoxic exposure caused alveolar expansion,
      thickening of alveolar septum, and fusion of adjacent alveoli into larger cysts
      under intermittent hypoxia in a time-dependent manner. Compared with the CG and
      HI groups, the mean lining interval (MLI) become more thickened and the alveolar
      destruction index (DI) increased significantly in the IH group. CONCLUSIONS
      Chronic intermittent hypoxia causes pulmonary inflammatory response and the
      inflammatory pathway involved in TLR4 receptor may be one of the mechanisms that
      trigger lung inflammation.

PMID- 30293086
TI  - Shaping human evolution.

PMID- 30293085
TI  - MicroRNA-183-5p Inhibits Aggressiveness of Cervical Cancer Cells by Targeting
      Integrin Subunit Beta 1 (ITGB1).
AB  - BACKGROUND Accumulating studies demonstrate that microRNAs play crucial roles in
      multiple processes of cancer progression. Lower levels of miR-183 have been
      observed in diverse types of tumors but the mechanism and precise function of miR
      183-5p in cervical cancer have largely not been investigated. MATERIAL AND
      METHODS The level of miR-183-5p in different cervical cancer cell lines and
      clinical tissues was detected qRT-PCR assays. Transwell and wound-healing
      migration assays were conducted to assess the functional roles of miR-183-5p in
      over-expressing cervical cancer cells in vitro. Rescue assays were carried out to
      confirm the contribution of integrin subunit Beta 1 (ITGB1) to the aggressiveness
      of cancer cells regulated by miR-183-5p. RESULTS miR-183-5p was reduced in
      clinical tissues of cervical cancer and cell lines when compared to the normal
      subjects and normal cervical epithelial cell line, respectively. In addition,
      over-expression of miR-183-5p markedly inhibited migration and invasion in
      cervical cancer cells, and increased aggressiveness was observed in miR-183-5p
      inhibitor transfected cells. Furthermore, the luciferase reporter assays revealed
      that ITGB1 was the gene directly regulated by miR-183-5p. Notably, a negative
      association between the ITGB1 and miR-183-5p was found, and the gene expressions
      of ITGB1 was mediated by miR-183-5p in cervical cancer cells. CONCLUSIONS miR-183
      5p serves as a latent anti-oncogene by targeting the metastasis-promoter gene,
      ITGB1.

PMID- 30293087
TI  - Relapse to opioid seeking in rat models: behavior, pharmacology and circuits.
AB  - Lifetime relapse rates remain a major obstacle in addressing the current opioid
      crisis. Relapse to opioid use can be modeled in rodent studies where drug self
      administration is followed by a period of abstinence and a subsequent test for
      drug seeking. Abstinence can be achieved through extinction training, forced
      abstinence, or voluntary abstinence. Voluntary abstinence can be accomplished by
      introducing adverse consequences of continued drug self-administration (e.g.,
      punishment or electric barrier) or by introducing an alternative nondrug reward
      in a discrete choice procedure (drug versus palatable food or social
      interaction). In this review, we first discuss pharmacological and circuit
      mechanisms of opioid seeking, as assessed in the classical extinction
      reinstatement model, where reinstatement is induced by reexposure to the self
      administered drug (drug priming), discrete cues, discriminative cues, drug
      associated contexts, different forms of stress, or withdrawal states. Next, we
      discuss pharmacological and circuit mechanisms of relapse after forced or
      voluntary abstinence, including the phenomenon of "incubation of heroin craving"
      (the time-dependent increases in heroin seeking during abstinence). We conclude
      by discussing future directions of preclinical relapse-related studies using
      opioid drugs.

PMID- 30293088
TI  - The COSMIC Cancer Gene Census: describing genetic dysfunction across all human
      cancers.
AB  - The Catalogue of Somatic Mutations in Cancer (COSMIC) Cancer Gene Census (CGC) is
      an expert-curated description of the genes driving human cancer that is used as a
      standard in cancer genetics across basic research, medical reporting and
      pharmaceutical development. After a major expansion and complete re-evaluation,
      the 2018 CGC describes in detail the effect of 719 cancer-driving genes. The
      recent expansion includes functional and mechanistic descriptions of how each
      gene contributes to disease generation in terms of the key cancer hallmarks and
      the impact of mutations on gene and protein function. These functional
      characteristics depict the extraordinary complexity of cancer biology and suggest
      multiple cancer-related functions for many genes, which are often highly tissue
      dependent or tumour stage-dependent. The 2018 CGC encompasses a second tier,
      describing an expanding list of genes (currently 145) from more recent cancer
      studies that show supportive but less detailed indications of a role in cancer.

PMID- 30293089
TI  - Sex differences in mortality after heat waves: are elderly women at higher risk?
AB  - BACKGROUND AND OBJECTIVE: Climate change leads to more frequent, intense and
      longer-lasting heat waves which can have severe health outcomes. The elderly are
      a high-risk population for heat-related mortality and some studies suggested that
      elderly women are more affected by extreme heat than men. This study aimed to
      review the presence of sex-specific results in studies performed on mortality in
      elderly (> 65 years old) after heat waves in Europe. METHODS: A literature search
      was conducted in July 2017 on papers published in databases Pubmed and Web of
      Science between January 2000 and December 2016. RESULTS: 68 papers that included
      mortality data for elderly after heat waves were identified. The 13 of them which
      presented results distinguished by sex and age group were included in the review.
      Eight studies showed worse health outcome for elderly women compared to men. One
      study showed higher mortality rates for men, two found no sex differences and two
      studies presented inconsistent results. CONCLUSION: Studies that present sex
      stratified data on mortality after heat waves seem to indicate that elderly women
      are at higher risk than men. Future research is warranted to validate this
      finding. Furthermore, a better understanding on the underlying physiological or
      social mechanisms for possible sex and gender differences in excessive deaths for
      this vulnerable population is needed to set up appropriate policy measures.

PMID- 30293091
TI  - The internal nasal valve: a validated grading system and operative guide.
AB  - PURPOSE: Nasal obstruction is a highly subjective and commonly reported symptom.
      The internal nasal valve (INV) is the rate limiting step to nasal airflow. A
      static INV grading score was devised with regard to visibility of the middle
      turbinate. METHODS: A prospective study of all patients who underwent primary
      external functional septorhinoplasty in 2017 for nasal obstruction. All patients'
      INV score was assessed pre- and postoperatively in a blinded and independent
      fashion by surgeons of varying seniority. RESULTS: Twenty-eight patients were
      studied, with mean age 30.9 years and follow-up 18.8 weeks. Inter-rater and test
      retest reliability of INV grading were excellent, with Cronbach's alpha 0.936 and
      0.920, respectively. There was also statistically significant improvement in both
      subjective and objective postoperative outcome measures including nasal
      inspiratory peak flows. CONCLUSIONS: We demonstrate a novel, easy to interpret,
      clinically valuable grading system of the static internal nasal valve that is
      reliable and reproducible.

PMID- 30293092
TI  - The Bear Giant-Skipper genome suggests genetic adaptations to living inside yucca
      roots.
AB  - Giant-Skippers (Megathymini) are unusual thick-bodied, moth-like butterflies
      whose caterpillars feed inside Yucca roots and Agave leaves. Giant-Skippers are
      attributed to the subfamily Hesperiinae and they are endemic to southern and
      mostly desert regions of the North American continent. To shed light on the
      genotypic determinants of their unusual phenotypic traits, we sequenced and
      annotated a draft genome of the largest Giant-Skipper species, the Bear
      (Megathymus ursus violae). The Bear skipper genome is the least heterozygous
      among sequenced Lepidoptera genomes, possibly due to much smaller population size
      and extensive inbreeding. Their lower heterozygosity helped us to obtain a high
      quality genome with an N50 of 4.2 Mbp. The ~ 430 Mb genome encodes about 14000
      proteins. Phylogenetic analysis supports placement of Giant-Skippers with Grass
      Skippers (Hesperiinae). We find that proteins involved in odorant and taste
      sensing as well as in oxidative reactions have diverged significantly in
      Megathymus as compared to Lerema, another Grass-Skipper. In addition, the Giant
      Skipper has lost several odorant and gustatory receptors and possesses many fewer
      (1/3-1/2 of other skippers) anti-oxidative enzymes. Such differences may be
      related to the unusual life style of Giant-Skippers: they do not feed as adults,
      and their caterpillars feed inside Yuccas and Agaves, which provide a source of
      antioxidants such as polyphenols.

PMID- 30293090
TI  - Long non-coding RNA AFAP1-AS1 plays an oncogenic role in promoting cell migration
      in non-small cell lung cancer.
AB  - Long non-coding RNA (lncRNA) plays an important role in tumor progression and
      metastasis. Emerging evidence indicates that lncRNA actin filament-associated
      protein 1-antisense RNA 1 (AFAP1-AS1) is dysregulated in certain tumors. However,
      the function of AFAP1-AS1 in non-small cell lung cancer (NSCLC) remains elusive.
      In this study, we conducted global lncRNA profiling and identified that AFAP1-AS1
      is significantly upregulated in NSCLC, suggesting that AFAP1-AS1 may be important
      for lung cancer development. For the first time, the transcription initiation and
      termination sites of AFAP1-AS1 were identified by rapid amplification of cDNA
      ends technology, and the sequencing data indicated that AFAP1-AS1 in lung cancer
      cells is a novel transcript variant. Through gain- and loss-of-function studies,
      AFAP1-AS1 was demonstrated to promote cell migration and invasion.
      Mechanistically, AFAP1-AS1 functions through positively regulating the expression
      of AFAP1 protein. On the other hand, the expression of lncRNA AFAP1-AS1
      negatively correlates with CpG methylation status of its gene promoter,
      identified in both lung cancer cells and patient tissues, and treatment with DNA
      methyltransferase inhibitor decitabine significantly activates AFAP1-AS1
      expression, strongly supporting that AFAP1-AS1 expression is tightly regulated by
      DNA methylation. Taken together, this study demonstrates that AFAP1-AS1 acts as
      an oncogene in NSCLC to promote cell migration partly by upregulating AFAP1
      expression, while its own expression is controlled by DNA methylation, and
      highlights its diagnostic and therapeutic values for NSCLC patients.

PMID- 30293093
TI  - Peer support opportunities across the cancer care continuum: a systematic scoping
      review of recent peer-reviewed literature.
AB  - OBJECTIVE: Evidence suggests peer support (PS) is as an effective strategy for
      enhancing prevention and control of chronic and infectious diseases, including
      cancer. This systematic scoping review examines the range and variety of
      interventions on the use of PS across the cancer care continuum. METHOD: We used
      a broad definition of PS to capture a wide-range of interventions and
      characterize the current status of the field. Literature searches were conducted
      using PubMed, SCOPUS, and CINAHL to identify relevant articles published from
      January 2011 to June 2016. We screened the title and abstracts of 2087 articles,
      followed by full-text screening of 420 articles, resulting in a final sample of
      242 articles of which the most recent 100 articles were reviewed (published June
      2014 to May 2016). RESULTS: A number of the recent intervention studies focused
      on breast cancer (32%, breast cancer only) or multiple cancer sites (23%).
      Although the interventions spanned all phases of the cancer care continuum, only
      2% targeted end-of-life care. Seventy-six percent focused on clinical outcomes
      (e.g., screening, treatment adherence) and 72% on reducing health disparities.
      Interventions were primarily phone-based (44%) or delivered in a clinic setting
      (44%). Only a few studies (22%) described the impact of providing PS on peer
      supporters. CONCLUSION: PS appears to be a widely used approach to address needs
      across the cancer care continuum, with many opportunities to expand its reach.

PMID- 30293095
TI  - Prevalence and predictors of atrial arrhythmias in patients with sinus node
      dysfunction and atrial pacing.
AB  - PURPOSE: This study aimed to determine the incidence, prevalence, and predictors
      of atrial arrhythmias (AAs) in patients with symptomatic sinus node dysfunction
      (SND) who required permanent pacemaker implantation. Also, we evaluated the
      impact of atrial pacing (AP) on AAs. METHODS: All consecutive patients who
      underwent pacemaker implantation from 2005 to 2011 were included. Atrial
      fibrillation (AF), atrial flutter (AFL), atrial tachycardia (AT), and AV nodal
      reentrant tachycardia (AVNRT) were detected via pacemaker interrogation and
      clinical documentation. RESULTS: The study group included 322 patients (44% male)
      with mean age 68.8 +/- 15 years and followed for an average of 5.6 +/- 2.2 years
      (median 5.7 years). Overall, 61.8% were found to have any AA at follow-up.
      Individual prevalence of AAs was high as follows: AF 43.5%, AFL 6.5%, AT 25%, and
      AVNRT 6.8%. AF was documented in 23% of patients (n = 74) prior to pacemaker;
      among those, 15% (n = 11) had no recurrence of AF with average AP of 74%. The
      incidence of new-onset AF after pacemaker was 15.8%. In subgroup analysis,
      prevalence of AF was increased by 16% with high rate of AP (81-100%) and 17% with
      lower rate of AP (0-20%). Incidence of new-onset AF was not affected by AP.
      Diabetes, hypertension, and left atrial enlargement were predictors of AAs. White
      men and women had higher prevalence of AF. CONCLUSIONS: AAs are highly prevalent
      in SND, particularly in white patients. Paroxysmal AF is suppressed with AP in
      minority, but there is no impact of AP on new-onset AF. Patients with diabetes,
      hypertension, and dilated atria must be monitored closely for early detection of
      AAs.

PMID- 30293094
TI  - The Role of Tau Imaging in Parkinsonian Disorders.
AB  - PURPOSE OF REVIEW: Differential diagnosis of atypical Parkinson syndromes (APS)
      is difficult as clinical presentations may vary and as there is a strong overlap
      between disease entities. Aggregations of misfolded and hyperphosphorylated tau
      proteins are the common denominator of many of these diseases. RECENT FINDINGS:
      Several tau targeting positron emission tomography (PET) tracers have been
      evaluated as possible biomarkers in APS in the recent years. For Parkinson's
      disease, dementia with Lewy bodies, progressive supranuclear palsy, and
      corticobasal degeneration, promising results have been reported with regard to
      the ability to detect the presence of disease and to discriminate patients from
      controls. However, the discussion about the specificity of the first-generation
      radiotracers and their value in the clinical context is ongoing. A combined
      interpretation of signal strength and distribution pattern in PET scans with
      first- and second-generation tracers may be helpful in clinical diagnosis and
      follow-up of patients with APS.

PMID- 30293096
TI  - Let's Open the Decision-Making Umbrella: A Framework for Conceptualizing and
      Assessing Features of Impaired Decision Making in Addiction.
AB  - Decision-making impairments play a pivotal role in the emergence and maintenance
      of addictive disorders. However, a sound conceptualization of decision making as
      an umbrella construct, encompassing its cognitive, affective, motivational, and
      physiological subcomponents, is still lacking. This prevents an efficient
      evaluation of the heterogeneity of decision-making impairments and the
      development of tailored treatment. This paper thus unfolds the various processes
      involved in decision making by adopting a critical approach of prominent dual- or
      triadic-process models, which postulate that decision making is influenced by the
      interplay of impulsive-automatic, reflective-controlled, and interoceptive
      processes. Our approach also focuses on social cognition processes, which play a
      crucial role in decision making and addictive disorders but were largely ignored
      in previous dual- or triadic-process models. We propose here a theoretical
      framework in which a range of coordinated processes are first identified on the
      basis of their theoretical and clinical relevance. Each selected process is then
      defined before reviewing available results underlining its role in addictive
      disorders (i.e., substance use, gambling, and gaming disorders). Laboratory tasks
      for measuring each process are also proposed, initiating a preliminary process
      based decision-making assessment battery. This original approach may offer an
      especially informative view of the constitutive features of decision-making
      impairments in addiction. As prior research has implicated these features as risk
      factors for the development and maintenance of addictive disorders, our
      processual approach sets the scene for novel and transdiagnostic experimental and
      applied research avenues.

PMID- 30293098
TI  - Burden of Migraine in Europe Using Self-Reported Digital Diary Data from the
      Migraine Buddy(c) Application.
AB  - INTRODUCTION: Migraine is a neurological disease characterized by recurring
      attacks that can cause severe disabling pain. This study described the burden of
      migraine as reported by individuals with migraine in the real world using a
      mobile application. METHODS: A retrospective, cross-sectional analysis was
      conducted using data captured through the Migraine Buddy(c) smartphone
      application from adult, self-diagnosed individuals with migraine in 17 European
      countries. Data were analyzed descriptively for the most recent 28-day period
      reported by users (n = 3900) during the study period (June 2015-July 2016) who
      were randomly selected on the basis of data completeness (completion rates > 70%)
      and stratified by migraine headache days/month: 4-7 episodic migraine (EM; n =
      1500), 8-14 EM (n = 1500), and chronic migraine (>= 15; CM; n = 900). RESULTS:
      More than 95% of users reported that migraine negatively affected their daily
      activities during at least one migraine attack. Attacks affected 50.5% (184.4
      days/year), 26.9% (98 days/year), and 14.5% (53 days/year) of the year among CM,
      8-14 EM, and 4-7 EM groups, respectively. On average, 44.8% CM, 40.9% 8-14 EM,
      and 34.7% of 4-7 EM sufferers, respectively, reported anxiety and/or depression
      symptoms during migraine attacks. Social or home activities, productivity, and
      sleep were highly affected, regardless of migraine frequency. Employed
      respondents (n = 3106) reported an average of 2.3 workdays missed per month and
      that at least one in four migraines led to work absenteeism; these migraines were
      commonly reported to have at least moderate to severe levels of pain,
      corresponding to the inability of persons to perform some or even any activities.
      Triptans (68%), opioids (46%), and nonsteroidal anti-inflammatory drugs (45%)
      were self-reported as the most common medicines used. CONCLUSIONS: This study,
      leveraging patient-reported data collected through a mobile application,
      demonstrates the high burden and impact of migraine on health-related quality of
      life, work productivity, and overall well-being of individuals suffering from
      migraines. FUNDING: Novartis Pharma AG, Switzerland.

PMID- 30293099
TI  - Laryngopharyngeal motor dysfunction and obstructive sleep apnea in Parkinson's
      disease.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is a common sleep disorder in Parkinson's
      disease (PD), but the relationship between these two conditions remains
      uncertain. Upper airway (UA) dysfunction in PD is well documented in some
      patients and is believed to be a reflex of the motor involvement of
      laryngopharyngeal muscles. The aim of this study is to determine whether UA
      dysfunction and laryngopharyngeal motor dysfunction (LMD) are involved in the
      obstructive phenomenon of OSA in PD. METHODS: Forty-eight PD patients underwent
      polysomnography for OSA diagnosis, functional evaluation of the UA by spirometry
      and a clinical protocol for analysis of laryngopharyngeal muscles and physical
      examination. RESULTS: Thirty-one participants (64.6%) fulfilled the criteria for
      OSA according to the International Classification of Sleep Disorders- third
      edition (at least respiratory disturbance index of five or higher per hour of
      sleep plus specific symptoms). UA obstruction was observed in 25% of participants
      and LMD in 60.4%. Among the clinical indicators of LMD, hypophonia was the most
      common (58.3%). Participants with LMD had a threefold greater chance of
      presenting with OSA than those without LMD did (OR = 3.49; 95% CI, 1.01-12.1; p =
      0.044). Individuals with LMD had more UA dysfunction (37.9 vs 10.5%, p = 0.037),
      higher scores on UPDRS III (20 vs 15, p = 0.0005) and the Hoehn-Yahr scale (2.5
      vs 2.0, p = 0.008), and higher frequencies of postural changes (51.7 vs 21.1%, p
      = 0.033) and motor phenomena (65.5 vs 31.6%, p = 0.021). Obesity, snoring, neck
      circumference, and the Mallampati score did not correlate with OSA in PD.
      CONCLUSION: LMD should be considered a factor that is involved in the obstructive
      phenomenon of UA in patients with OSA and PD.

PMID- 30293100
TI  - Spontaneous cardiac baroreflex sensitivity is enhanced during post-exercise
      ischemia in men but not in women.
AB  - PURPOSE: To investigate the effect of isolated muscle metaboreflex activation on
      spontaneous cardiac baroreflex sensitivity (cBRS), and to characterize the
      potential sex-related differences in this interaction in young healthy subjects.
      METHODS: 40 volunteers (20 men and 20 women, age: 22 +/- 0.4 year) were
      recruited. After 5-min rest period, the subjects performed 90 s of isometric
      handgrip exercise at 40% of maximal voluntary contraction followed by 3 min of
      post-exercise ischemia (PEI). Beat-to-beat heart rate and arterial blood pressure
      were continuously measured by finger photopletysmography. Spontaneous cBRS was
      assessed using the sequence technique and heart rate variability was measured in
      time (RMSSD-standard deviation of the RR intervals) and frequency domains (LF-low
      and HF-high frequency power). RESULTS: Resting cBRS was similar between men and
      women. During PEI, cBRS was increased in men (Delta3.0 +/- 1.1 ms mmHg- 1, P =
      0.03) but was unchanged in women (Delta-0.04 +/- 1.0 ms mmHg- 1, P = 0.97). In
      addition, RMSSD and HF power of heart rate variability increased in women
      (Delta7.4 +/- 2.6 ms, P = 0.02; Delta373.4 +/- 197.3 ms2; P = 0.04, respectively)
      and further increased in men (Delta26.4 +/- 7.1 ms, P < 0.01; Delta1874.9 +/-
      756.2 ms2; P = 0.02, respectively). Arterial blood pressure increased from rest
      during handgrip exercise and remained elevated during PEI in both groups,
      however, these responses were attenuated in women. CONCLUSIONS: These findings
      allow us to suggest a sex-related difference in spontaneous cBRS elicited by
      isolated muscle metaboreflex activation in healthy humans.

PMID- 30293097
TI  - Suicide Risk and the Menstrual Cycle: a Review of Candidate RDoC Mechanisms.
AB  - PURPOSE OF REVIEW: Risk for suicidal behavior may fluctuate across the menstrual
      cycle. Here, we use the RDoC framework to review potential mechanisms by which
      the cycle may increase acute suicide risk. RECENT FINDINGS: The menstrual cycle
      impacts the majority of RDoC constructs linked to suicide risk, particularly
      among hormone-sensitive women, such as those with premenstrual dysphoric disorder
      or premenstrual exacerbation of a psychiatric disorder. Despite this, there are
      no published studies examining suicidal ideation, planning, or behavior
      longitudinally across the cycle. More work is needed to understand how hormone
      sensitivity may relate to both trait and state suicide risk. Intensive multilevel
      investigations of cyclical hormone effects on suicide risk through specific RDoC
      mechanisms are suggested. This is a fertile research area and may provide key
      insights regarding the mechanisms of acute suicide risk.

PMID- 30293101
TI  - Measurement properties of self-report questionnaires on health-related quality of
      life and functional health status in dysphonia: a systematic review using the
      COSMIN taxonomy.
AB  - PURPOSE: The current review was conducted to identify all self-report
      questionnaires on functional health status (FHS) and/or health-related quality-of
      life (HR-QoL) in adult populations with dysphonia (voice problems), and to
      evaluate the psychometric properties of the retrieved questionnaires. METHODS: A
      systematic review was performed in the electronic literature databases PubMed and
      Embase. The psychometric properties of the questionnaires were determined using
      the COnsensus-based Standards for the selection of health Measurement INstruments
      (COSMIN) taxonomy and checklist. Responsiveness was outside the scope of this
      review and as no agreed 'gold standard' measures are available in the field of
      FHS and HR-QoL in dysphonia, criterion validity was not assessed. Only
      questionnaires developed and published in English were included. RESULTS: Forty
      eight studies reported on the psychometric properties of 15 identified
      questionnaires. As many psychometric data were missing or resulted from biased
      study designs or statistical analyses, only preliminary conclusions can be drawn.
      Based on the current available psychometric evidence in the literature, the Voice
      Handicap Index seems to be the most promising questionnaire, followed by the
      Vocal Performance Questionnaire. CONCLUSIONS: More research is needed to complete
      missing data on psychometric properties of existing questionnaires in FHS and/or
      HR-QoL. Further, when developing new questionnaires, the use of item response
      theory is preferred above classical testing theory, as well as international
      consensus-based psychometric definitions and criteria to avoid bias in outcome
      data on measurement properties.

PMID- 30293102
TI  - Development of novel sericin and alginate-based biosorbents for precious metal
      removal from wastewater.
AB  - In this study, two novel low water-soluble sericin and alginate-based biosorbents
      were successfully developed for precious metal removal from wastewater: sericin
      and alginate particles chemically crosslinked by proantocyanidins (SAPAs) and
      sericin, alginate and polyvinyl alcohol particles (SAPVA). The proportions of
      proantocynidins (PAs) or polyvinyl alcohol (PVA) added to sericin (2.5% w/v) and
      alginate (2.0% w/v) blend were 0.5, 1.5, 2.5 and 3.5% w/v. Among these
      concentrations, particles produced with 0.5% w/v of PVA or 2.5% w/v of PAs
      presented the lowest water solubility percentages (3.74 +/- 0.05 and 3.56 +/-
      0.21%, respectively) and the following metallic affinity order: AuCl4- > PdCl42-
      > PtCl62- > Ag+. Then, gold biosorption kinetics by SAPAs was evaluated at three
      gold initial concentrations (72.88, 187.12, and 273.79 mg/L), and its performance
      was compared to activated carbon adsorbent uptake. The data modeling revealed
      that the process follows pseudo-first-order kinetics and is mainly controlled by
      external diffusion. SAPAs before and after gold biosorption (SAPAs-gold) were
      characterized by scanning electron microscopy coupled with energy dispersive X
      ray spectroscopy, optical microscopy, helium pycnometry, mercury porosimetry, N2
      physisorption, and Fourier-transform infrared spectroscopy.

PMID- 30293104
TI  - Adsorption of ibuprofen using cysteine-modified silane-coated magnetic
      nanomaterial.
AB  - Industrialization and growth of the pharmaceutical companies have been a boon to
      the mankind in our day to day life in myriad ways. However, due to the
      uninhibited release of these active pharmaceutical compounds into the water
      systems has caused detrimental effects to the genetic pool. In this study, L
      cysteine-modified 3-glycidyloxypropyltrimethoxysilane-coated magnetic
      nanomaterial showed a maximum removal of the efficiency of 82.90% for the
      nanomaterial dosage of 30 mg at an initial concentration of 50 mg L-1 at pH 6.0.
      Further, the nanomaterial showed reusability efficiency up to 80% for three
      cycles. The adsorption kinetics follow the pseudo-second-order reaction and the
      adsorption isotherm model best fits the Langmuir isotherm proving the adsorption
      process to be a monolayer sorption on a monolayer surface. This magnetic
      nanomaterial could serve as a promising tool for the removal of pharmaceutical
      compounds from aqueous solutions. Graphical abstract ?.

PMID- 30293103
TI  - Modelling as decision support for the localisation of submarine urban wastewater
      outfall: Venice lagoon (Italy) as a case study.
AB  - Microbiological impact is critical in coastal areas where tourism is particularly
      important for both the local and regional economy. Submarine outfalls are
      commonly used to enhance the dispersion of treated sewage thus avoiding pollution
      along the coast. The Venice lagoon (North Italy) has a very sensitive ecosystem,
      due to the morphological and natural characteristics of the basin and the co
      existence of human activities. To preserve the lagoon, the discharge from the
      treatment plant for urban wastewater collected from the Venezia-Mestre
      agglomeration, neighbouring areas and local industries (total of 400,000
      population equivalent-PE) has been moved from the lagoon to the open Adriatic Sea
      since November 2013 by means of an approximately 20-km pipeline. Microbiological
      pollution inside the lagoon can affect shellfish breeding areas instead, along
      the coast it affects the quality of bathing waters. In this study, and for the
      first time, a 3D hydrodynamic SHYFEM model (shallow water finite element model)
      with high spatial resolution coupled with a microbiological module has been
      applied to the lagoon and to the Adriatic Sea, to evaluate the effectiveness of
      the location of the submarine outfall. Microbiological data have been produced by
      the control Authority according to official analytic methods and by the plant
      operator. The module of survival of free Escherichia coli follows a variable rate
      in dependence of UV radiation, temperature and salinity in the water. Two
      scenarios were modelled: final discharge into the lagoon before November 2013 and
      after into the open sea. In the latter case, two situations have been considered,
      one with "Bora" and the other with "Scirocco" winds. Our results indicate that
      the model correctly simulates microbiological decay and dispersion. The
      transferral of the final discharge point far from the shoreline improves
      pollution dispersion, thus preserving the lagoon without evidence of impacts on
      the bathing waters in all meteorological conditions.

PMID- 30293105
TI  - Chitosan nanoparticles from Artemia salina inhibit progression of hepatocellular
      carcinoma in vitro and in vivo.
AB  - This study was conducted to evaluate the effect of chitosan nanoparticles (CNPs)
      isolated from Artemia salina against hepatocellular carcinoma (HCC) both in vitro
      (HepG2) and in vivo (diethylnitrosamine-induced HCC in rats) and to investigate
      the involved underlying mechanisms. Administration of CNPs decreased HCC
      progression as evidenced by (1) induced HepG2 cell death as detected by MTT
      assay; (2) induced necrosis as indicated by acridine orange/propidium iodide
      (AO/PI) red staining, annexin V/7-AAD positive staining (detected by flow
      cytometry), and upregulated expression of necrosis markers (PARP1 and its
      downstream target, RIP1 genes), but no effect on apoptosis as revealed by
      insignificant changes in caspase 3 activity and mRNA levels of Bax and AIF; (3)
      increased intracellular ROS and decreased mitochondrial membrane potential in
      HepG2; (4) decreased liver relative weight, serum levels of liver enzymes (ALT,
      AST, and ALP), total bilirubin, and cancer markers (AFP and GGT), number and area
      of GST-P positive tumor nodules; and (5) reduced oxidative stress (decrease in
      MDA levels) and increased activities of SOD, CAT, and GPx enzymes in rat liver.
      The preventive (pre-treatment) effect of CNPs was better than the therapeutic
      (post-treatment) effect. Collectively, administration of CNPs inhibited HCC
      progression in vitro and in vivo, possibly through induction of necrosis, rather
      than apoptosis, and induction of antioxidant enzyme activities in vivo, but with
      stimulation of ROS production in vitro. Thus, CNPs could be used as a promise
      agent for treating HCC after application of further confirmatory clinical trials.

PMID- 30293106
TI  - Molecular isolation and characterization of the kisspeptin system, KISS and GPR54
      genes in roach Rutilus rutilus.
AB  - The reproduction of vertebrates is regulated by endocrine and neuro-endocrine
      signaling molecules acting along the brain-pituitary-gonad (BPG) axis. The
      understanding of the neuroendocrine role played in reproductive function has been
      recently revolutionized since the KiSS1/GPR54 (KiSS1r) system was discovered in
      2003 in human and mice. Kisspeptins, neuropeptides that are encoded by the KiSS
      genes, have been recognized as essential in the regulation of the gonadotropic
      axis. They have been shown to play key roles in puberty onset and reproduction by
      regulating the gonadotropin secretion in mammals while physiological roles in
      vertebrates are still poorly known. In order to provide new knowledge on basic
      reproductive physiology in fish as well as new tools to assess impacts of
      endocrine disrupting compounds (EDCs), the neurotransmitter system, i.e.,
      gene/receptor, KISS/GPR54 might constitute an appropriate biomarker. This study
      provides new understandings on the neuroendocrine regulation of roach
      reproduction as well as new molecular tools to be used as biomarkers of endocrine
      disruption. This work completes the set of biomarkers already validated in this
      species.

PMID- 30293107
TI  - Effect of a 12-week mixed power training on physical function in dynapenic-obese
      older men: does severity of dynapenia matter?
AB  - INTRODUCTION: Mobility disability affects nearly 15% of people aged 65 or over
      worldwide. Excess weight or obesity (OB), along with an accentuated loss of
      muscle strength (dynapenia), is recognized to be one of the most common risk
      factors for mobility impairment among the elderly. OBJECTIVE: To investigate the
      effect of a 12-week mixed power training (MPT high-velocity resistance training
      mixed with functional exercises) on physical function in obese older men
      exhibiting different severities of dynapenia. METHODS: Community-dwelling older
      men (69 +/- 6 years) were assigned to the study if they were considered obese
      (OB, fat mass >= 25% body weight, BW) and to one of the two groups according to
      severity of dynapenia [(handgrip strength-HS)/BW]: type 1(OB-DY1) or type 2(OB
      DY2), < 1 or 2SD from a young reference group. Participants followed a 12-week
      MPT, three times/week, 75 min/session. Main outcomes included the performance on
      the 4-m and 6-min walking tests, Timed Up and Go, stair and balance tests.
      RESULTS AND DISCUSSION: At baseline, OB-DY1 performed better than OB-DY2 in all
      functional tests (p < 0.05). Following the intervention, medium-to-large training
      effect size (ES) were observed for fat (ES = 0.21) and lean (ES = 0.32, p <
      0.001) masses, functional performance (ES 0.11-0.54, p < 0.05), HS (ES = 0.10, p
      < 0.05) and lower limb muscle strength (ES = 0.67, p < 0.001) and power (ES =
      0.60, p < 0.05). Training-by-group interaction showed that OB-DY1 lost more FM
      (ES = 0.11, p = 0.03) and OB-DY2 improved more HS (ES = 0.19, p = 0.006) than
      their counterparts. CONCLUSIONS: Seniors with obesity and severe dynapenia have
      poorer physical function than those in the early stage of dynapenia. Both seem to
      benefit from a high-velocity resistance training mixed with functional exercises,
      although by slightly different pathways.

PMID- 30293108
TI  - Diurnal variation of renal resistive index over 24-hour period in hypertensive
      patients and healthy controls.
AB  - PURPOSE: There are no data in the literature to our knowledge related to changes
      in renal resistive index (RRI) values over 24-h period and the importance of
      detecting these changes in patients who have hypertension (HT). In this study, we
      aimed to investigate the variation of RRI values over 24-h period and its
      usability in hypertensive patients. METHODS: A total of 118 subjects (80 with HT
      and 38 healthy controls) were included in the study. Morning, midday, evening,
      and midnight RRI, renal pulsatility index, and accelerated time were measured by
      Doppler ultrasonography (US). B-mode US and elastograpic assessment were
      performed only in the morning. RESULTS: Temporal RRI varied significantly (p <
      0.001). The highest and lowest levels were found in the morning and evening,
      respectively. All temporal RRI levels were significantly higher in patients with
      HT (both p < 0.001). The absolute and relative increases in RRI (DeltaRRI) levels
      were similar in two groups. All temporal RRI measurements positively correlated
      with the patient age, pulse pressure, renal cortical thickness, and cortical
      stiffness. However, absolute-DeltaRRI and relative-DeltaRRI positively correlated
      with the age. Absolute-DeltaRRI positively correlated with the pulse pressure and
      cortical stiffness, and no correlation was observed between relative-DeltaRRI and
      these variables. Of the four temporal measurements, morning RRI were found to be
      independently associated with cortical stiffness (p < 0.001). CONCLUSIONS: RRI
      measurements varied over 24-h period in patients with HT and/or healthy controls.
      Morning RRI was significantly higher than other day time, and it is also related
      to renal cortical stiffness.

PMID- 30293109
TI  - Differentiation of duodenal gastrointestinal stromal tumors from hypervascular
      pancreatic neuroendocrine tumors in the pancreatic head using contrast-enhanced
      computed tomography.
AB  - PURPOSE: To determine useful contrast-enhanced computed tomography (CE-CT)
      features in differentiating duodenal gastrointestinal stromal tumors (duodenal
      GISTs) from hypervascular pancreatic neuroendocrine tumors in the pancreatic head
      (pancreatic head NETs). METHODS: Seventeen patients with pathologically confirmed
      duodenal GISTs and 25 with pancreatic NETs underwent preoperative CE-CT. CT image
      analysis included tumor size, morphology, and contrast enhancement. Receiver
      operating characteristic curves were performed, and cutoff values were calculated
      to determine CT findings with high sensitivity and specificity. RESULTS: CT
      imaging showed duodenal GISTs with higher frequencies of tumor central location
      close to the duodenum and a predominantly solid tumor type when compared with
      pancreatic head NETs (p < 0.05 for both). Duodenal GISTs were larger than
      pancreatic head NETs (3.3 +/- 0.9 cm vs. 2.5 +/- 1.1 cm, p = 0.03). Duodenal
      GISTs had significantly lower CT attenuation values (112.9 +/- 17.9HU vs. 137.4
      +/- 32.1HU, p < 0.01) at the arterial phase and higher CT attenuation values at
      the delayed phase (94.3 +/- 7.9HU vs. 84.9 +/- 10.4HU, p < 0.01) when compared
      with pancreatic head NETs. A CT attenuation value of <= 135 HU at the arterial
      phase (30 s) was 76% sensitive, 94.1% specific, and 83.3% accurate for the
      diagnosis of duodenal GISTs, while a CT attenuation value of >= 89.5 HU at the
      delayed phase (120 s) was 93.3% sensitive, 81.8% specific, and 76.2% accurate for
      the diagnosis of duodenal GISTs. CONCLUSION: Tumor central location, size,
      texture, and contrast enhancement are valuable characteristics for the
      differentiation between duodenal GISTs and hypervascular pancreatic head NETs
      during preoperative examination.

PMID- 30293110
TI  - Short-term and long-term effects of immunoadsorption in refractory chronic
      inflammatory demyelinating polyneuropathy: a prospective study in 17 patients.
AB  - OBJECTIVE: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare,
      autoimmune-inflammatory disease of the peripheral nervous system. Recently,
      various immunoglobulin G4 (IgG4) type auto-antibodies have been described in
      patients with CIDP which can effectively be removed by immunoadsorption (IA).
      Therefore, we prospectively evaluated the therapeutic effect of IA in 17 patients
      with progressive CIDP not responding to other treatment. METHODS: We
      prospectively evaluated the course of disease of 17 patients with CIDP who had
      insufficiently responded to steroids and/or IVIg previously and who received at
      least one cycle of IA. As clinical outcome parameter, we used a combined CIDP
      score of three validated scales comprising disability, motor score, and
      sensitivity. Seven patients received repeated treatments in regular intervals
      over a prolonged period up to 46 months. RESULTS: We observed a small, but
      significant improvement of the overall score after 2 weeks that mainly reflected
      an improvement of muscle strength. The median value of the combined CIDP score
      was 308.0 (266.0-374.5) points before IA and 330.0 (290.0-393.5) points 2 weeks
      after IA (p = 0.019). More importantly, all but one of seven progressive patients
      who received long-term immunoadsorption in regular intervals stabilized almost
      completely. Before IA, these patients lost 6.7 (3.0-13.1) points of combined CIDP
      score per month. During IA, they lost - 0.1 (0.0-0.8) points per month (p <
      0.0001). INTERPRETATION: Our results suggest that IA might constitute a promising
      and well-tolerated therapeutic alternative in CIDP for short-term and long-term
      treatment. We showed that long-term treatment with IA in regular intervals can
      stabilize the course of disease at least in a subgroup of patients.

PMID- 30293112
TI  - Basal fatty acid oxidation increases after recurrent low glucose in human primary
      astrocytes.
AB  - AIMS/HYPOTHESIS: Hypoglycaemia is a major barrier to good glucose control in type
      1 diabetes. Frequent hypoglycaemic episodes impair awareness of subsequent
      hypoglycaemic bouts. Neural changes underpinning awareness of hypoglycaemia are
      poorly defined and molecular mechanisms by which glial cells contribute to
      hypoglycaemia sensing and glucose counterregulation require further
      investigation. The aim of the current study was to examine whether, and by what
      mechanism, human primary astrocyte (HPA) function was altered by acute and
      recurrent low glucose (RLG). METHODS: To test whether glia, specifically
      astrocytes, could detect changes in glucose, we utilised HPA and U373 astrocytoma
      cells and exposed them to RLG in vitro. This allowed measurement, with high
      specificity and sensitivity, of RLG-associated changes in cellular metabolism. We
      examined changes in protein phosphorylation/expression using western blotting.
      Metabolic function was assessed using a Seahorse extracellular flux analyser.
      Immunofluorescent imaging was used to examine cell morphology and enzymatic
      assays were used to measure lactate release, glycogen content, intracellular ATP
      and nucleotide ratios. RESULTS: AMP-activated protein kinase (AMPK) was activated
      over a pathophysiologically relevant glucose concentration range. RLG produced an
      increased dependency on fatty acid oxidation for basal mitochondrial metabolism
      and exhibited hallmarks of mitochondrial stress, including increased proton leak
      and reduced coupling efficiency. Relative to glucose availability, lactate
      release increased during low glucose but this was not modified by RLG. Basal
      glucose uptake was not modified by RLG and glycogen levels were similar in
      control and RLG-treated cells. Mitochondrial adaptations to RLG were partially
      recovered by maintaining euglycaemic levels of glucose following RLG exposure.
      CONCLUSIONS/INTERPRETATION: Taken together, these data indicate that HPA
      mitochondria are altered following RLG, with a metabolic switch towards increased
      fatty acid oxidation, suggesting glial adaptations to RLG involve altered
      mitochondrial metabolism that could contribute to defective glucose
      counterregulation to hypoglycaemia in diabetes.

PMID- 30293113
TI  - A cost analysis of intensified vs conventional multifactorial therapy in
      individuals with type 2 diabetes: a post hoc analysis of the Steno-2 study.
AB  - AIMS/HYPOTHESIS: Long-term follow-up of the Steno-2 study demonstrated that
      intensified multifactorial intervention increased median lifespan by 7.9 years
      and delayed incident cardiovascular disease by a median of 8.1 years compared
      with conventional multifactorial intervention during 21.2 years of follow-up. In
      this post hoc analysis of data from the Steno-2 study, we aimed to study the
      difference in direct medical costs associated with conventional vs intensified
      treatment. METHODS: In 1993, 160 Danish individuals with type 2 diabetes and
      microalbuminuria were randomised to conventional or intensified multifactorial
      target-driven intervention for 7.8 years. Information on direct healthcare costs
      was retrieved from health registries, and the costs in the two groups of
      participants were compared by bootstrap t test analysis. RESULTS: Over 21.2 years
      of follow-up, there was no difference in total direct medical costs between the
      intensified treatment group, ?12,126,900, and the conventional treatment group,
      ?11,181,700 (p = 0.48). The mean cost per person-year during 1996-2014 was
      significantly lower in the intensified treatment group (?8725 in the intensive
      group and ?10,091 in the conventional group, p = 0.045). The main driver of this
      difference was reduced costs associated with inpatient admissions related to
      cardiovascular disease (p = 0.0024). CONCLUSIONS/INTERPRETATION: Over a follow-up
      period of 21.2 years, we found no difference in total costs and reduced cost per
      person-year associated with intensified multifactorial treatment for 7.8 years
      compared with conventional multifactorial treatment. Considering the substantial
      gain in life-years and health benefits achieved with intensified treatment, we
      conclude that intensified multifaceted intervention in high-risk individuals with
      type 2 diabetes seems to be highly feasible when balancing healthcare costs and
      treatment benefits in a Danish healthcare setting.

PMID- 30293114
TI  - Cinnamaldehyde inhibit Escherichia coli associated with membrane disruption and
      oxidative damage.
AB  - In this study, the antimicrobial mechanism of cinnamaldehyde (CIN) against Gram
      negative Escherichia coli ATCC 25922 (E. coli) based on membrane and gene
      regulation was investigated. Treatment with low concentration (0, 1/8, 1/4, 3/8
      MIC) of CIN can effectively suppress the growth of E. coli by prolonging its lag
      phase and Raman spectroscopy showed obvious distinction of the E. coli after
      being treated with these concentration of CIN. The determination of relative
      conductivity indicated that CIN at relatively high concentration (0, 1, 2, 4 MIC)
      can increase the cell membrane permeability, causing the leakage of cellular
      content. Besides, the content of malondialdehyde (MDA) and the activity of total
      superoxide dismutase (SOD) of E. coli increased with increasing treatment
      concentration of CIN, implying that CIN can cause oxidative damage on E. coli
      cell membrane and induce the increase of total SOD activity to resist this
      oxidative harm. Moreover, quantitative real-time RT-PCR (qRT-PCR) analysis
      revealed the relationship between expression of antioxidant genes (SODa, SODb,
      SODc) and treatment CIN concentration, suggesting that SOD, especially SODc,
      played a significant role in resistance of E. coli to CIN. The underlying
      inactivation processing of CIN on E. coli was explored to support CIN as a
      potential and natural antimicrobial agent in food industry.

PMID- 30293111
TI  - Management of patients with stroke treated with direct oral anticoagulants.
AB  - Since their market approval, direct oral anticoagulants (DOACs) are being
      increasingly used for stroke prevention in patients with atrial fibrillation.
      However, the management of DOAC-treated patients with stroke poses several
      challenges for physicians in everyday clinical practice, both in the acute
      setting and in long-term care. This has spurred extensive research activity in
      the field over the past few years, which we review here.

PMID- 30293115
TI  - Letter to Editor concerning "Comparative study of the efficacy of transdermal
      buprenorphine patches and prolonged-release tramadol tablets for postoperative
      pain control after spinal fusion surgery: a prospective, randomized controlled
      non-inferiority trial" by Kim HJ, Ahn HS, Nam Y, Chang BS, Lee CK, Yeom JS (2017)
      Eur Spine J 26:2961-2968.

PMID- 30293116
TI  - A review on iron chelators as potential therapeutic agents for the treatment of
      Alzheimer's and Parkinson's diseases.
AB  - Iron plays a vital role in several cellular functions due to its unique
      physiochemical properties. Iron concentration increases in the brain with age due
      to multiple factors. Excessive amount of iron can lead to formation of reactive
      oxygen species. Neurodegenerative disorders are characterized by iron
      supplemented increase in oxidative stress and cellular damage. There is an urgent
      need of novel therapies which should not only provide symptomatic relief but also
      be able to modulate iron accumulation in the brain. Therefore, the development of
      novel iron chelators as neuroprotective agents for the treatment of
      neurodegeneration is an emerging trend. Several iron chelators including 8
      hydroxyquinoline derivatives, dopaminergic agonists and natural products are
      under preclinical and clinical investigations for the treatment of
      neurodegenerative disorders.

PMID- 30293117
TI  - Apatinib as maintenance therapy in extensive-stage small-cell lung cancer:
      results from a single-center retrospective study.
AB  - PURPOSE: To evaluate the efficacy of maintenance apatinib after chemotherapy for
      extensive-stage (ED) small-cell lung cancer (SCLC). PATIENTS AND METHODS: This
      was a retrospective analysis of 23 cases of extensive-stage SCLC admitted to the
      Affiliated Cancer Hospital of Zhengzhou University from January 2015 to December
      2017. The patients without progression after induction chemotherapy received
      apatinib 250 mg per day until disease progression or unacceptable toxicity
      occurred. We analyzed the median progression-free survival (PFS), median overall
      survival (OS) and safety. RESULTS: Of 23 enrolled patients, 1 was lost to follow
      up. The median PFS from the time of maintenance therapy was 4.1 months (95% CI
      3.63-4.57 months). The median PFS from the time of induction chemotherapy was 8.3
      months (95% CI 7.20-9.40 months). The median OS from the time of maintenance
      therapy was 12.5 months (95% CI 5.51-19.49 months). The median OS from the time
      of induction chemotherapy was 17.0 months (95% CI 9.86-24.14 months). The most
      frequent treatment-related adverse events were hand-foot syndrome (43.5%, 10/23)
      and secondary hypertension (30.4%, 7/23), followed by fatigue, proteinuria,
      nausea, and oral mucositis (17.4%, 13.0%, 13.0%, and 8.7%, respectively).
      Hematologic toxicity included thrombocytopenia (30.4%), leucopenia (26.1%), and
      anemia (17.4%). The main grade 3 or 4 toxicities were hand-foot syndrome (8.7%,
      2/23) and hypertension (4.3%, 1/23). CONCLUSION: Maintenance apatinib was safe
      and achieved encouraging PFS and OS in extensive-stage SCLC.

PMID- 30293118
TI  - Progress in gene therapy using oncolytic vaccinia virus as vectors.
AB  - BACKGROUND: Vaccinia virus was widely used in the World Health Organization's
      smallpox eradication campaign and is currently a promising vector for gene
      therapy owing to its unique characteristics. Vaccinia virus can selectively
      replicate and propagate productively in tumor cells, resulting in oncolysis. In
      addition, rapid viral particle production, wide host range, large genome size
      (approximately 200 kb), and safe handling render vaccinia virus a suitable vector
      for gene therapy. MATERIALS AND METHODS: Cancer vaccines and gene therapy are
      being studied in clinical trials and experiment researches. However, we put
      forward unique challenges of optimal selection of foreign genes, administration
      and modification of VACV, personalized medicine, and other existing problems,
      based on current researches and our own experiments. CONCLUSION: This review
      presents an overview of the vaccinia virus from its mechanisms to medical
      researches and clinical trials. We believe that the solution to these problems
      will contribute to understanding mechanisms of VACV and provide a theoretical
      basis for clinical treatment.

PMID- 30293119
TI  - Pre-treatment metabolic tumor volume predicts tumor metastasis and progression in
      high-grade salivary gland carcinoma.
AB  - PURPOSE: High-grade salivary gland carcinoma (SGC) shows a high rate of
      metastasis and post-treatment recurrence, resulting in poor patient survival.
      Therefore, we evaluated the utility of pre-treatment 18F-FDG PET/CT parameters in
      predicting metastasis, tumor progression, and survival of high-grade SGC
      patients. METHODS: This observational study included 75 patients with previously
      untreated high-grade SGC who underwent pre-treatment 18F-FDG PET/CT scanning and
      subsequent treatment. Standardized uptake values (SUV), metabolic tumor volume
      (MTV), and total lesion glycolysis (TLG) were measured on pre-treatment 18F-FDG
      PET/CT. Logistic regression analysis was used to identify the relationship of
      these factors with metastasis. Cox proportional hazard regression analyses were
      used to identify associations between PET parameters and both progression-free
      survival (PFS) and overall survival (OS). RESULTS: A total of 36 (48%) patients
      had neck or distant metastases at initial staging. After controlling for clinical
      factors, MTV (> 8.8 mL) was an independent factor for initial metastasis
      (adjusted odds ratio 4.80, 95% confidence interval 1.09-21.20; P = 0.039). All
      PET parameters of SUVmax (> 4.3), SUVmean (> 3.0), SUVpeak (3.9), MTV (> 8.8 mL),
      and TLG (> 31.1 g) were significant variables for PFS (all P < 0.05), while MTV
      and TLG were significant factors for OS. After controlling for
      clinicopathological factors, MTV (adjusted hazard ratio 4.36, 95% confidence
      interval 1.69-11.26; P = 0.002) and TLG (3.41, 1.47-7.91; P = 0.004) were
      significantly associated with PFS, but not OS. CONCLUSIONS: MTV is useful among
      quantitative PET measurements for predicting initial metastasis and PFS in
      patients with high-grade SGC.

PMID- 30293121
TI  - Relative age and ADHD symptoms, diagnosis and medication: a systematic review.
AB  - There is a growing international literature investigating the relationship
      between attention-deficit/hyperactivity disorder (ADHD) and younger relative age
      within the school year, but results have been mixed. There are no published
      systematic reviews on this topic. This study aimed to systematically review the
      published studies on the relative age effect in ADHD. Systematic database
      searches of: Medline, Embase, PsycINFO, Web of Science, ERIC, Psychology and
      Behavioral Sciences Collection and The Cochrane Library were conducted. Studies
      were selected which investigated the relative age effect in ADHD in children and
      adolescents. Twenty papers were included in the review. Sixteen (of 20) papers
      reported a significantly higher proportion of relatively younger children being
      diagnosed with ADHD and/or receiving medication for this. Meta-analyses involving
      17 of these 20 papers revealed a modest relative age effect in countries with
      higher prescribing rates, risk ratio = 1.27 (95% CI 1.19-1.35) for receipt of
      medication. The relative age effect is well demonstrated in countries with known
      higher prescribing rates. Amongst other countries, there is also increasing
      evidence for the relative age effect, however, there is high heterogeneity
      amongst studies. Further research is needed to understand the possible reasons
      under-pinning the relative age effect and to inform attempts to reduce it.

PMID- 30293120
TI  - Kaposiform hemangioendothelioma without cutaneous involvement.
AB  - PURPOSE: We sought to characterize the clinical features and management of
      patients diagnosed as Kaposiform hemangioendothelioma (KHE) without cutaneous
      involvement. METHODS: The electronic patient chats at six Triple A hospitals in
      China were searched to find all patient diagnoses with KHE without cutaneous
      involvement. RESULTS: Of 30 patients (mean age at diagnosis, 55.6 months), 17
      (56.7%) were male. Fourteen (46.7%) patients were associated with Kasabach
      Merritt phenomenon (KMP). Patients with KMP were significantly more likely to
      have lesions involving truck compared to patients without KMP (odds ratio 10.000;
      95% confidence interval 1.641-60.921; P = 0.011). Other common complication
      included severe anemia and decreased range of motion. In the majority of cases
      (93.3%), the lesions were highly infiltrative and locally invasive with ill
      defined margins. Histological examination was required in all patients without
      KMP for precise diagnosis. In all, 16 (53.3%) patients received corticosteroid
      treatment, 19 (63.3%) received oral sirolimus treatment, 7 (23.3%) received
      intravenous vincristine, and 5 (16.7%) patients used propranolol. Patients had
      varied responses to conventional drugs, whereas all patients receiving sirolimus
      treatment had better response. In all, three patients (10%) died of disease, all
      presented with KMP. Feature of these recalcitrant cases (death) included young
      age, visceral location, extensive involvement, and lack of improvement with high
      dose corticosteroids. CONCLUSIONS: Our study clearly demonstrated that KHE
      without cutaneous involvement could be associated with important complication,
      which might result in death or severe morbidity. Increased awareness of KHE
      without cutaneous involvement is required for early diagnosis and aggressive
      therapy in an attempt to prevent complication.

PMID- 30293122
TI  - Suicidal behaviors and irritability in children and adolescents: a systematic
      review of the nature and mechanisms of the association.
AB  - While many psychiatric disorders are associated with an increased risk for
      suicidal behaviors (SB) in children and adolescents, a few studies have explored
      the role of clinical symptoms based on a dimensional approach. Irritability is
      seen as a marker, a general psychopathology, and a symptom of both externalizing
      and internalizing disorders. In this review, we are interested in determining
      whether and how irritability can predict SB in youth. First, we reviewed
      consistencies and variation in the literature linking irritability to suicidal
      ideation (SI) and suicide attempt (SA). Second, based on the available models, we
      proposed specific mechanistic pathways, whereby irritability may modulate the
      risk for SB. Irritability has been found associated with SB both in cross
      sectional and in longitudinal studies. The relation is consistent in different
      settings (i.e., general population and clinical settings) and across psychiatric
      disorders. The association is reduced but persists after adjusting for
      psychiatric disorder, including depression. On one hand, irritability constitutes
      a risk factor for SI via the onset of internalized disorder. On the other hand,
      irritable youth may be more prone to attempt suicide when experiencing SI. The
      measures for irritability were heterogeneous. A limited number of studies were
      designed to explore the role of mediators and/or moderators. Recognizing
      irritability in children and adolescents is a key issue with regards to suicide
      prevention.

PMID- 30293123
TI  - Low back pain in Brazilian medical students: a cross-sectional study in 629
      individuals.
AB  - Low back pain (LBP) is a common problem in the general population. Medical
      students may be at risk of LBP because of demanding curricula. To study the
      prevalence of LBP in Brazilian medical students and the associated factors. Six
      hundred twenty-nine medical students (72.8% females, mean age of 23 years old)
      answered a questionnaire containing epidemiological data; data on presence and
      frequency of LBP, use of painkillers, and LBP interference in daily activities;
      number of sitting and exercising hours/day, posture habits. They also filled a
      VAS (or visual analogic scale) on the own perception of anxiety, depression,
      fatigue, and the Roland Morris functional questionnaire for LBP. In this sample,
      81.7% had periods of recurrent LBP that was more common in females (77.6% vs
      51.3%; p < 0.0001) and associated with bad posture habits (p < 0.0001). Number of
      sitting hours, exercising, and study period at school could not be associated
      with LBP. The mean Roland Morris result was 4.0; IQR = 2-7 and its value showed a
      modest correlation with VAS of anxiety (rho = 0.21) and depression (rho = 0.33).
      LBP interfered with social activities in 20.5%, with physical activities in
      33.1%, and in school activities in 29.2%. There is a high prevalence of LBP in
      medical students, mainly females, associated with bad posture habits. Physical
      dysfunction for LBP showed correlation with anxiety and depression.

PMID- 30293125
TI  - Visfatin and insulin levels and cigarette smoking are independent risk factors
      for hidradenitis suppurativa: a case-control study.
AB  - Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. HS has been
      associated with obesity, adipokine imbalance, dyslipidemia, pro-inflammation, and
      metabolic syndrome (MS). The aim of this study was to determine the association
      between HS, and serum visfatin levels (SVLs), small-dense low-density lipoprotein
      cholesterol (sdLDL-C), and ischemia-modified albumin (IMA), as well as the
      association between HS, and smoking, alcohol consumption, anthropometric
      measurements, blood pressures (BPs), fasting blood glucose (FBG) and lipids,
      inflammatory markers, homocysteine, uric acid (UA), serum insulin levels (SILs),
      insulin resistance (IR) and MS, so as to identify relevant risk factors for HS.
      This case-control study included 40 patients (M/F: 23/17) and 40 age- and gender
      matched controls (M/F: 23/17). Demographic data, smoking status and alcohol
      consumption, personal and family medical history, previous and current treatments
      were noted. Anthropometric data, BPs, FBG and lipids, homocysteine, UA,
      erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and high
      sensitivity CRP (hs-CRP), hemoglobin A1c (HbA1c), SILs, SVLs, IMA and sdLDL-C
      were measured. Homeostasis model assessment for IR (HOMA-IR) was calculated. The
      associations were made by univariate and multivariate analyses. Univariate
      analysis showed that there was a significant association between HS and smoking,
      pack-years of smoking, weight, body mass index (BMI), waist circumference (WC),
      triglycerides (TGs), high-density lipoprotein cholesterol, very low-density
      lipoprotein cholesterol, SILs, CRP, hs-CRP, homocysteine, UA, ESR, HOMA-IR, SVLs,
      and MS. After adjusting for BMI and smoking status, the SVLs, SILs, and hs-CRP
      levels remained higher in the patients than in the controls (P = 0.02, P = 0.01,
      and P = 0.02, respectively). Multivariate analysis showed that there was a
      significant association between HS, and the SVLs and SILs, and smoking. Each unit
      increase in the SVL (P = 0.003, 95% CI 1.16-2.11) and SIL (P = 0.03, 95% CI 1.01
      1.17) increased the risk of HS 1.56- and 1.09-fold, respectively. Furthermore,
      smoking was associated with a 14.87-fold increase in the risk of HS (P = 0.001,
      95% CI 2.82-78.56). This study indicates that HS patients have higher SVLs, SILs,
      and hs-CRP levels than healthy controls-independent of BMI and smoking status.
      The SVL and SILs and smoking were independent risk factors for HS.

PMID- 30293124
TI  - Mono-exponential and bi-exponential model-based diffusion-weighted MR imaging and
      IDEAL-IQ sequence for quantitative evaluation of sacroiliitis in patients with
      ankylosing spondylitis.
AB  - To evaluate the utility of mono-exponential and bi-exponential model-based
      diffusion-weighted MR imaging and IDEAL-IQ sequence for differentiating the
      activity of sacroiliitis in ankylosing spondylitis (AS). AS patients were divided
      into active group (n = 30) and inactive group (n = 28) according to Ankylosing
      Spondylitis Disease Activity Score (ASDAS) with C-reactive protein (CRP). In
      addition, 30 healthy volunteers were chosen as healthy group. Subjects were
      scanned by conventional MRI, diffusion-weighted imaging, and IDEAL-IQ sequence.
      Apparent diffusion coefficient (ADC), true diffusion coefficient (D),
      pseudodiffusion coefficient (D*), perfusion fraction (f), and fat fraction (FF)
      values were measured, and their relative values (rADC, rD, rD*, rf) were
      calculated by the formula ADC (D,D*,f)lesion/ADC (D,D*,f)reference, respectively.
      The ADC, D, rADC, and rD of active group were the highest among the three groups,
      followed by inactive and healthy group. However, D* and rD* showed no significant
      difference among the three groups. FF was significantly higher in inactive group
      than in healthy and active group. ADC and D had significantly higher AUCs than f
      for differentiating active group from healthy group, while FF had the highest AUC
      for distinguishing inactive sacroiliitis from healthy group. DWI and IDEAL-IQ
      imaging are helpful in quantitatively assessing the activity of sacroiliitis in
      AS patients.

PMID- 30293126
TI  - Rivaroxaban versus Warfarin in Patients with Mechanical Heart Valve: Rationale
      and Design of the RIWA Study.
AB  - INTRODUCTION: Mechanical heart valves (MHV) are extremely durable, but they
      require permanent use of anticoagulation to prevent thromboembolic events. The
      only approved therapeutic options are vitamin K antagonists (VKAs), such as
      warfarin. As a drug class, clinical management is difficult, therefore new
      alternatives need to be evaluated. METHODS: RIWA is a phase II/III, prospective,
      open-label, randomized, pilot study designed to investigate oral rivaroxaban 15
      mg twice daily compared with dose-adjusted warfarin for the prevention of stroke
      (ischemic or hemorrhagic) and systemic embolism in patients with MHV, from August
      2018 to December 2019. Patients will undergo transesophageal echocardiography at
      the beginning and the end of the study (follow-up time 90 days). On an
      explanatory basis, all events will be analyzed, including stroke, peripheral
      systemic embolism, valve thrombosis, significant bleeding and death. DISCUSSION:
      Warfarin and similar VKAs are standard therapy for patients with an MHV. Even
      with the appropriate use of therapy, the incidence of thromboembolic events is
      high at 1-4% per year. Furthermore, bleeding risk is significant, ranging from 2
      to 9% per year. The new frontier to be overcome in relation to use of the new
      oral anticoagulants is undoubtedly in patients with MHV. A significant portion of
      people with MHV worldwide will benefit if noninferiority of these new agents is
      confirmed. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03566303.
      Recruitment Status: Recruiting. First Posted: 25 June 2018. Last Update Posted:
      25 June 2018.

PMID- 30293128
TI  - Functional Behavior-Based Cognitive-Behavioral Therapy for Obsessive Compulsive
      Behavior in Children with Autism Spectrum Disorder: A Randomized Controlled
      Trial.
AB  - Children with autism spectrum disorder (ASD) experience obsessions and
      compulsions similar to those specified in DSM-5 for obsessive compulsive disorder
      yet little controlled research exists on treating these behaviours. Thirty-seven
      children (7-13 years old) were randomly assigned to a 9-week functional behavior
      based cognitive behavior therapy (Fb-CBT) or Treatment As Usual. Independent
      assessors administered measures pre- and post-treatment and at 6-months. Two
      primary outcome measures indicated statistically significant differences between
      groups, with large corrected effect sizes (Hedge's g = 1.00 and 1.15,
      respectively). This is the first known RCT to exclusively treat obsessive
      compulsive behaviors (OCBs) in children and youth with high functioning (IQ >=
      70) ASD, and suggests that Fb-CBT treatment shows promise in decreasing these
      behaviors and improving quality of life. Trial Registration This trial was
      registered with ClinicalTrials.gov (ID: NCT03123146).

PMID- 30293129
TI  - Combination of Soy Protein, Amylopectin, and Chromium Stimulates Muscle Protein
      Synthesis by Regulation of Ubiquitin-Proteasome Proteolysis Pathway after
      Exercise.
AB  - The present study was undertaken to investigate the effect of the combination of
      soy protein, amylopectin, and chromium (SAC) on muscle protein synthesis and
      signal transduction pathways involved in protein synthesis (mTOR pathways, IGF-1,
      and AktSer473) and proteolysis (FOXO1Ser256; MURF1, MAFbx) after exercise. Thirty
      five Wistar rats were randomly divided into five groups: (1) control (C); (2)
      exercise (E); (3) exercise + soy protein (3.1 g/kg/day) (E + S); (4) exercise +
      soy protein + chromium (E + S + Cr); (5) exercise + soy protein + amylopectin +
      chromium (E + S + A + Cr). Post-exercise ingestion of SAC significantly increased
      the fractional rate of protein synthesis (FSR), insulin, glycogen, and amino acid
      levels with the highest effect observed in E + S + A + Cr group (P ? 0.05).
      However, SAC supplementation decreased the lactic acid concentration (P ? 0.05).
      A reduction in forkhead box protein O1 (FOXO1) and forkhead box protein O3
      (FOXO3) (regulators of ubiquitin-related proteolysis) and muscle atrophy F-box
      (MAFbx) levels was noted after treatment with SAC (P < 0.05). Insulin-like growth
      factor 1(IGF-1) level was increased in the E + S, E + S + Cr, and E + S + A + Cr
      groups (P < 0.05). While the phosphorylation of 4E-BP1Thr37/46, AktSer473,
      mTORSer2448, and S6K1Thr389 levels increased after SAC supplementation,
      phosphorylated muscle ring finger 1 (MuRF-1, an E3-ubiquitin ligase gene) was
      found to be significantly lower compared with the E group (P ? 0.05). These
      results indicate that SAC supplementation improves FSR, insulin, and glycogen
      levels after exercise. SAC improves protein synthesis by inhibiting the ubiquitin
      proteasome pathway and inducing anabolic metabolism.

PMID- 30293127
TI  - Coexpression of octopine and succinamopine Agrobacterium virulence genes to
      generate high quality transgenic events in maize by reducing vector backbone
      integration.
AB  - Agrobacterium-mediated transformation is a complex process that is widely
      utilized for generating transgenic plants. However, one of the major concerns of
      this process is the frequent presence of undesirable T-DNA vector backbone
      sequences in the transgenic plants. To mitigate this deficiency, a ternary strain
      of A. tumefaciens was modified to increase the precision of T-DNA border nicking
      such that the backbone transfer is minimized. This particular strain supplemented
      the native succinamopine VirD1/VirD2 of EHA105 with VirD1/VirD2 derived from an
      octopine source (pTi15955), the same source as the binary T-DNA borders tested
      here, residing on a ternary helper plasmid containing an extra copy of the
      succinamopine VirB/C/G operons and VirD1. Transformation of maize immature
      embryos was carried out with two different test constructs, pDAB101556 and
      pDAB111437, bearing the reporter YFP gene and insecticidal toxin Cry1Fa gene,
      respectively, contained in the VirD-supplemented and regular control ternary
      strains. Molecular analyses of ~ 700 transgenic events revealed a significant 2.6
      fold decrease in events containing vector backbone sequences, from 35.7% with the
      control to 13.9% with the VirD-supplemented strain for pDAB101556 and from 24.9%
      with the control to 9.3% with the VirD-supplemented strain for pDAB111437,
      without compromising transformation efficiency. In addition, while the number of
      single copy events recovered was similar, there was a 24-26% increase in backbone
      free events with the VirD-supplemented strain compared to the control strain.
      Thus, supplementing existing VirD1/VirD2 genes in Agrobacterium, to recognize
      diverse T-DNA borders, proved to be a useful tool to increase the number of high
      quality events in maize.

PMID- 30293130
TI  - Semen Uranium Concentrations in Depleted Uranium Exposed Gulf War Veterans:
      Correlations with Other Body Fluid Matrices.
AB  - Environmental metal exposure, as well as dietary metals, may adversely affect
      semen quality even as others play an essential role in normal spermatogenesis and
      fertility. Measures of seminal fluid metals have therefore been of high interest
      in the last several decades but have shown inconsistent results in correlations
      with some semen quality parameters. As well, environmental metal measures across
      various body fluid matrices have not been consistently correlated contrary to
      what one might hypothesize based on a systemic body burden of metal. This may be
      due to the body fluid matrices assessed and to other differences in laboratory
      methods and sample preparation. Measures of uranium, a potentially toxic metal in
      humans, have not previously been reported in the semen of environmentally metal
      exposed populations. We report here uranium seminal fluid results and the high
      correlation of uranium concentrations across several body fluid matrices in a
      cohort of military veterans exposed to depleted uranium in combat events during
      the Iraqi Gulf War. These results inform the risk communication conversation for
      exposed populations and broaden the public health assessments from various
      exposure scenarios.

PMID- 30293131
TI  - Enhancement in Iron Absorption on Intake of Chemometrically Optimized Ratio of
      Probiotic Strain Lactobacillus plantarum 299v with Iron Supplement Pearl Millet.
AB  - This research article aims to establish the intake ratio of probiotic
      Lactobacillus plantarum 299v with iron supplement pearl millet by central
      composite design of response surface methodology so as to enhance iron
      absorption. In anemic rat models, the food intake pattern, body weight,
      hemoglobin content, and hematocrit values were found to be significantly
      increased on treatment with pearl millet:probiotic; however, incorporation of
      probiotics at lower dose (0.5 g) was significantly (p < 0.05) effective in
      enhancing iron absorption, and further increment in probiotic doses (1.0 g) did
      not produce significant increase in hemoglobin and hematocrit values as evidenced
      by the experimental findings.

PMID- 30293132
TI  - A family case of X-linked Alport syndrome patients with a novel variant in
      COL4A5.
AB  - We herein report 2 Japanese patients with X-linked Alport syndrome (XLAS), with a
      novel variant in COL4A5. Patient 1 was a 16-year-old Japanese girl with a history
      of microscopic hematuria, without proteinuria, renal dysfunction, deafness, or
      ocular abnormalities. At 13 years of age, renal biopsy was performed; however, a
      diagnosis of AS was not considered. When her mother (patient 2) was 40 years of
      age (3 years after patient 1 underwent a renal biopsy), patient 2 was found to
      have asymptomatic hematuria, proteinuria, and an increased serum creatinine
      level, without deafness and ocular abnormalities. Subsequently,
      immunofluorescence staining for alpha 5 chains of type IV collagen was performed
      in patient 1. Pathological findings were consistent with AS, and genetic analysis
      demonstrated that both patients had a heterozygous mutation in COL4A5
      (NM_000495.4: exon41:c.C3769T: p.Q1257X). To date, more than 900 different COL4A5
      mutations have been identified; however, this variant has not been previously
      described. Physicians have to consider AS when they perform a renal biopsy in all
      patients with hematuria despite absent/present of family history, hearing loss,
      and ocular abnormality. Especially, when findings of light microscopy and
      immunofluorescence microscope are unclear, it should be considered carefully.
      Electron microscopy findings are very important.

PMID- 30293133
TI  - Gut Microbiota Imbalance Can Be Associated with Non-malabsorptive Small Bowel
      Shortening Regardless of Blind Loop.
AB  - INTRODUCTION: Some traditional bariatric surgery procedures may lead to
      functional gut shortening, which may unsettle the fine-tuned gastrointestinal
      physiology and affect gut microbiota balance. PURPOSE: Evaluate the gut
      microbiota behavior in rat models facing gut shortening due to intestinal bypass.
      MATERIALS AND METHODS: Wistar rats (n = 17) were randomly distributed in three
      groups: (1) sham group (n = 5); (2) blind loop group (n = 6); and (3) resection
      group (n = 6). Intestinal samples and feces were analyzed to measure bacterial
      concentrations (small intestinal bacterial overgrowth-SIBO) 12 weeks after the
      experimental procedures. Bacterial translocation (BT) was investigated in the
      mesenteric lymph node (MLN), liver, spleen, and lung of the animals. In addition,
      inflammatory aspects were investigated in their liver and small bowel through
      histological analysis. RESULTS: Regardless of blind loop, gut shortening groups
      recorded similar high level of bacterial concentrations in intestine
      compartments, greater than that of the sham group (p <= 0.05). BT was only
      observed in the MLN of gut shortening models, with higher percentage in the blind
      loop group (p <= 0.05). The gut and liver histopathological analysis showed
      similar low-grade chronic inflammation in both gut shortening groups, likely
      associated with SIBO/BT events. CONCLUSION: Sustained SIBO/BT was associated with
      proximal gut shortening in half regardless of blind loop, whereas the GI tract's
      ability to restore gut microbiota balance after a surgical challenge on the small
      bowel appears to be linked to the functional remaining gut.

PMID- 30293134
TI  - Long-Term Outcomes After Bariatric Surgery: a Systematic Review and Meta-analysis
      of Weight Loss at 10 or More Years for All Bariatric Procedures and a Single
      Centre Review of 20-Year Outcomes After Adjustable Gastric Banding.
AB  - INTRODUCTION: Durability is a key requirement for the broad acceptance of
      bariatric surgery. We report on durability at and beyond 10 years with a
      systematic review and meta-analysis of all reports providing data at 10 or more
      years and a single-centre study of laparoscopic adjustable gastric banding (LAGB)
      with 20 years of follow-up. METHODS: Systematic review with meta-analysis was
      performed on all eligble reports containing 10 or more years of follow-up data on
      weight loss after bariatric surgery. In addition, a prospective cohort study of
      LAGB patients measuring weight loss and reoperation at up to 20 years is
      presented. RESULTS: Systematic review identified 57 datasets of which 33 were
      eligible for meta-analysis. Weighted means of the percentage of excess weight
      loss (%EWL) were calculated for all papers included in the systematic review.
      Eighteen reports of gastric bypass showed a weighted mean of 56.7%EWL, 17 reports
      of LAGB showed 45.9%EWL, 9 reports of biliopancreatic bypass +/- duodenal switch
      showed 74.1%EWL and 2 reports of sleeve gastrectomy showed 58.3%EWL. Meta
      analyses of eligible studies demonstrated comparable results. Reoperations were
      common in all groups. At a single centre, 8378 LAGB patients were followed for up
      to 20 years with an overall follow-up rate of 54%. No surgical deaths occurred.
      Weight loss at 20 years (N = 35) was 30.1 kg, 48.9%EWL and 22.2% total weight
      loss (%TWL). Reoperation rate was initially high but reduced markedly with
      improved band and surgical and aftercare techniques. CONCLUSION: All current
      procedures are associated with substantial and durable weight loss. More long
      term data are needed for one-anastomosis gastric bypass and sleeve gastrectomy.
      Reoperation is likely to remain common across all procedures.

PMID- 30293135
TI  - Short-Term Outcomes of Conversion of Failed Gastric Banding to Laparoscopic
      Sleeve Gastrectomy or Roux-En-Y Gastric Bypass: a Meta-Analysis.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is associated with
      high long-term failure rates, often requiring conversion to an alternative
      bariatric procedure. The most efficacious procedure after failed LAGB is subject
      to debate. Our objective was to compare 12-month weight loss following
      laparoscopic sleeve gastrectomy (LSG) vs. laparoscopic Roux-en-Y gastric bypass
      (LRYGB) performed for insufficient weight loss or weight regain after LAGB.
      METHODS: A systematic search was conducted in PubMed and Medline for English
      language studies comparing weight loss after a conversion surgery for failed
      gastric banding. We examined studies with patients who had at least 1-year follow
      up and included conversions to both LSG and LRYGB. A fixed effects model was
      created, and variance measures were calculated to measure heterogeneity. Both
      were analyzed for significance. All statistical analyses were conducted with the
      "meta" package in R 3.3.2. RESULTS: The initial search produced 17 studies. Six
      studies, consisting of 205 LSG and 232 LRYGB patients, met our inclusion criteria
      and were included in the review. Heterogeneity among studies was high (Q = 23.1;
      p < 0.001). There was no statistically significant difference in weight loss
      after 12 months between the groups (p = 0.14). CONCLUSIONS: It remains unknown
      which conversion procedure is more appropriate to perform after a failed gastric
      band in order to achieve the highest weight loss potential. In our meta-analysis,
      there was no difference in weight loss after 12 months in patients who were
      converted to LSG or LRYGB. Further studies and longer follow-up comparisons are
      required before firm conclusions can be drawn.

PMID- 30293137
TI  - Fetal brain morphometry on prenatal magnetic resonance imaging in congenital
      diaphragmatic hernia.
AB  - BACKGROUND: Many infants with congenital diaphragmatic hernia (CDH) show brain
      abnormality on postnatal brain MRI related to severity of CDH, degree of lung
      hypoplasia, intrathoracic liver, right diaphragmatic hernia and large
      diaphragmatic defect. It is not known whether these factors affect brain growth
      in utero in CDH. OBJECTIVE: To assess prenatal brain morphometry and
      abnormalities on fetal MR in congenital diaphragmatic hernia. MATERIALS AND
      METHODS: We retrospectively reviewed 109 fetal MRIs in 63 fetuses with CDH from
      2009 to 2014 (27 died before discharge, 36 survived to discharge). We compared
      brain injury and gestational-age-corrected z-scores of brain measurements between
      survivors and non-survivors. We assessed correlations between brain abnormalities
      and CDH severity. RESULTS: Enlarged extraaxial space was the most common
      abnormality, frequently seen on fetal MRI at >28 weeks of gestation, similar in
      survivors versus non-survivors. Anteroposterior cerebellar vermis dimension at
      >28 weeks of gestation was smaller in non-survivors compared to survivors (P=.02)
      and positively correlated with observed/expected total fetal lung volume (P=.01).
      Transverse cerebellar diameter at >28 weeks of gestation was also positively
      correlated with observed/expected total fetal lung volume (P=.04). We did not
      identify maturational delay, abnormal parenchymal signal or intracranial
      hemorrhage on fetal MRI. CONCLUSION: Enlarged extraaxial spaces in the third
      trimester was the most common abnormality on fetal MRI in congenital
      diaphragmatic hernia. Cerebellar dimensions on fetal MRI are associated with CDH
      severity. There was no major brain parenchymal injury on fetal MRI, even in the
      third trimester, in CDH survivors and non-survivors.

PMID- 30293138
TI  - Pancreatic heterotopia in a neonatal abdominopelvic cyst.
AB  - Pancreatic heterotopia is a rare congenital anomaly more commonly incidentally
      found in adults. While intra-abdominal cysts found on prenatal imaging are not
      uncommon, we examine a case of pancreatic heterotopia presenting in an
      abdominopelvic cyst on prenatal imaging. At birth, the neonate was found to have
      hypoglycemia unresponsive to treatment that resolved after cyst resection. We
      will review the etiology, imaging findings and clinical course of this anomaly,
      which should be considered in the differential diagnosis of newborns presenting
      with unexplained hypoglycemia.

PMID- 30293136
TI  - Nuclear calcineurin is a sensor for detecting Ca2+ release from the nuclear
      envelope via IP3R.
AB  - In continuously beating cells like cardiac myocytes, there are rapid alterations
      of cytosolic Ca2+ levels. We therefore hypothesize that decoding Ca2+ signals for
      hypertrophic signaling requires intracellular Ca2+ microdomains that are partly
      independent from cytosolic Ca2+. Furthermore, there is a need for a Ca2+ sensor
      within these microdomains that translates Ca2+ signals into hypertrophic
      signaling. Recent evidence suggested that the nucleus of cardiac myocytes might
      be a Ca2+ microdomain and that calcineurin, once translocated into the nucleus,
      could act as a nuclear Ca2+ sensor. We demonstrate that nuclear calcineurin was
      able to act as a nuclear Ca2+ sensor detecting local Ca2+ release from the
      nuclear envelope via IP3R. Nuclear calcineurin mutants defective for Ca2+ binding
      failed to activate NFAT-dependent transcription. Under hypertrophic conditions
      Ca2+ transients in the nuclear microdomain were significantly higher than in the
      cytosol providing a basis for sustained calcineurin/NFAT-mediated signaling
      uncoupled from cytosolic Ca2+. Measurements of nuclear and cytosolic Ca2+
      transients in IP3 sponge mice showed no increase of Ca2+ levels during diastole
      as we detected in wild-type mice. Nuclei, isolated from ventricular myocytes of
      mice after chronic Ang II treatment, showed an elevation of IP3R2 expression
      which was dependent on calcineurin/NFAT signaling and persisted for 3 weeks after
      removal of the Ang II stimulus. These data provide an explanation how Ca2+ and
      calcineurin might regulate transcription in cardiomyocytes in response to
      neurohumoral signals independently from their role in cardiac contraction
      control. KEY MESSAGES: * Calcineurin acts as an intranuclear Ca2+ sensor to
      promote NFAT activity. * Nuclear Ca2+ in cardiac myocytes increases via IP3R2
      upon Ang II stimulation. * IP3R2 expression is directly dependent on
      calcineurin/NFAT.

PMID- 30293139
TI  - Anti-CD37 targeted immunotherapy of B-Cell malignancies.
AB  - CD37 is a member of tetra-spanning superfamily (characterized by their four
      transmembrane domains). It is one of the specific proteins for normal and
      malignant mature B cells. Anti CD37 monoclonal antibodies are reported to improve
      the overall survival in CLL. These therapeutics will increase the efficacy and
      reduce the toxicity in patients with both newly diagnosed and relapsed and
      refractory disease. Recent clinical trials have shown promising outcomes for
      these agents, administered both as monotherapy and in combination with standard
      chemotherapeutics. Long-term follow-up of combination regimens has even raised
      the question of whether the patients with CLL could be treated with intensive
      chemo-immunotherapy. In the present study, CD37 is introduced as an appealing
      target to treat B cell malignancies. The anti-CD37 antibodies as one of the most
      successful therapeutics against CD37 are introduced and the clinical outcomes of
      their exploitation are explained.

PMID- 30293141
TI  - Total knee arthroplasty in Italy: reflections from the last fifteen years and
      projections for the next thirty.
AB  - PURPOSE: Annual rates of knee arthroplasty are increasing in all developed
      countries, imposing a significant economic and organizational burden; it is
      crucial to forecast the future need for knee arthroplasty, to assist stakeholders
      in planning strategies and investments, especially in a country like Italy, with
      the largest proportion of elderly citizens in Europe. Few epidemiological studies
      have been performed worldwide to estimate the demand for future knee replacement,
      and a variety of methods have been proposed. METHODS: We investigated the
      epidemiology of knee arthroplasty performed in Italy in the last 15 years and
      projected incidence rates up to the year 2050, utilizing, comparing, and adapting
      the available methodologies. RESULTS: From 2001 to 2016, 812,639 primary TKA were
      performed in Italy on patients over 40. The total number of surgeries increased
      by 262% with an average annual growth rate of 6.6%. CONCLUSIONS: Adopting the
      best fitting projection method, an increase of 45% in incidence rate is expected
      for 2050.

PMID- 30293143
TI  - How neuraxial labor analgesia differs by approach: dural puncture epidural as a
      novel option.
AB  - BACKGROUND AND AIM: Neuraxial analgesia techniques are not limited to just
      standard epidural and CSE blocks. A novel approach called dural puncture epidural
      (DPE) which is a modification of CSE in terms of practice has gained popularity
      after its description and use in the obstetric population.  The aim of this
      review is to address the practice of DPE technique as a novel option by reviewing
      its benefits as well as side and/or adverse effects and to understand how
      neuraxial labor analgesia differs by approach based on the information available
      in the current literature DISCUSSION: Despite controversies and concerns, more
      rapid onset of analgesia, early bilateral sacral analgesia, lower incidence of
      asymmetric block and fewer maternal and fetal side effects are provided with DPE
      when compared to epidural. CONCLUSION: DPE offers a favorable risk-benefit ratio
      for management of neuraxial analgesia as a novel option.

PMID- 30293144
TI  - Uses of the Past: History as a Resource for the Present.
AB  - Collective memory has become an increasingly important topic in social and human
      sciences over the past thirty years. Beyond the interest for how we understand
      history, collective memory research has explored how the past has been used to
      defend certain understandings of the world (for instance nationalist ideologies),
      political actions (as in the case of intractable conflicts), or collective
      identities (particularly when they are seen as reflecting the historical
      'essence' of a national group). That is, how the history is used as a resource
      for the present. However, theoretical conceptualisations have more directly
      focused on how collective memory is produced, and less so on how it is mobilised
      for the present. In this paper, we propose to review the main conceptualisation
      of collective memory in psychology - as social thinking, as social identity, and
      as sense-making - and how they more or less implicitly understand the relations
      between past and present. In a final section, we argue that representations of
      history have mainly been seen, in collective memory research, as a source of
      meaning for the present or as a way to position oneself in the current social
      field. In conclusion, we propose a third way of understanding the relations
      between past and present, considering collective memory to be both transformative
      of the present and prospective for the future.

PMID- 30293145
TI  - Plain radiograghs of lumbar spine in patients with low back pain.
AB  - : Low back pain (LBP) is a common presenting complaint in our hospital in Enugu
      Nigeria. Three hundred thirty-three radiographs of patients with LBP were
      studied. A lot of them had bony outgrowths (osteophytes) on the spine. Plain
      radiograph of the spine is useful in studying these patients' condition.
      INTRODUCTION: Low back pain (LBP) is one of the common symptoms which bring
      patients to hospital and ultimately to radiology department for medical
      assistance. Plain radiographs of lumbar spine are usually the initial imaging
      tools requested by clinicians. The objective of this study is to evaluate
      commonest finding in patients with LBP to guide physicians for improved
      management. METHODS: This work was a retrospective study. Plain films of these
      patients with LBP at the University of Nigeria Teaching Hospital, Enugu, were
      assessed by two radiologists. Findings documented and analyzed using IBM'S SPSS
      22. Association was determined using chi-square with level of significance, p <
      0.05. RESULTS: Total number of radiographs reviewed was 333. One hundred and
      eighty-three (55.0%) patients were females. Age ranged from 14 to 101 years. Mean
      age of 53.4 +/- 15.9 years. Disc space was normal in majority (55.3%, 184/333) of
      patients; narrowing was observed in most others (43.2%, 144/333), about half of
      the narrowing occurring along with vacuum phenomenon. Osteophytes were commonest
      finding in a total of 284/333 (85.3%) existing alone or in combination with other
      findings. Proportion of patients with osteophytes was highest in sixth to eighth
      decade of life (98.8% of 61-80 age group), followed by 41-60 age group (92.9%).
      This association between age group and the presence of osteophytes was
      statistically significant (p < 0.000). Anterior vertebral body was affected in
      85.0% (284/333) of patients. CONCLUSIONS: Osteophytes are common radiologic
      features in LBP. Anterior vertebral body is most affected. It is commoner in the
      older age group. Plain radiograph is an invaluable imaging tool in the management
      of LBP in this part of the world.

PMID- 30293142
TI  - Angiotensin II-mediated suppression of synaptic proteins in mouse hippocampal
      neuronal HT22 cell was inhibited by propofol: role of calcium signaling pathway.
AB  - PURPOSE: Angiotensin II (Ang II) has been shown to be involved in neurological
      disorders. Propofol demonstrated neuroprotective effects in neurons. METHODS:
      Mouse hippocampal HT22 cells were pre-treated with propofol, followed by Ang II
      treatment. The expression of synaptic proteins (synapsin I and PSD95) was
      examined. The effects of propofol on Ang II-induced NADPH oxidase expression and
      superoxide anion generation were examined. The effects of propofol on
      intracellular calcium concentration, the activation of calcium/calmodulin
      dependent protein kinase II (CaMKII), and protein kinase C (PKC) were measured.
      RESULTS: Ang II reduced the expression of synapsin I and PSD95, which was
      attenuated by propofol. Ang II-induced effects were blocked by Ang II type 1
      receptor (AT1 receptor) blocker. Ang II induced the expression of NADPH oxidase
      and caused superoxide anion accumulation, which were attenuated by propofol. In
      addition, propofol induced intracellular calcium concentration, and activated
      CaMKII as well as PKCbeta. Importantly, the Ang II-mediated effects were
      diminished by alpha-tocopherol, and the propofol-mediated effects were alleviated
      by calcium chelator, CaMKII inhibitor, and PKCbeta inhibitor. CONCLUSION: Ang II,
      via AT1 receptor, induced oxidative stress and reduced the expression of synapsin
      I and PSD95 in HT22 cells. Propofol may increase synapsin I and PSD95 expression
      by inhibiting oxidative stress and stimulating calcium signaling pathway.

PMID- 30293146
TI  - The non-visualized appendix and secondary signs on ultrasound for pediatric
      appendicitis in the community hospital setting.
AB  - BACKGROUND: Secondary signs of appendicitis on ultrasound may aid with diagnosis
      in the setting of a non-visualized appendix (NVA). This role has not been shown
      in the community hospital setting. MATERIALS AND METHODS: All right lower
      quadrant ultrasounds performed in children for clinical suspicion of appendicitis
      over a 5-year period in a single community hospital were evaluated. Secondary
      signs of inflammation including free fluid, ileus, fat stranding, abscess, and
      lymphadenopathy were documented. Patients were followed for 1 year for the
      primary outcome of appendicitis. These data were analyzed to determine the
      utility of secondary signs in the diagnosis of acute appendicitis when an NVA is
      reported. RESULTS: Six hundred and seventeen ultrasounds were reviewed; 470 of
      these had an NVA. Of NVAs, 47 (10%) of patients were diagnosed with appendicitis.
      Sensitivity and specificity of having at least one secondary were 38.3% and 80%,
      respectively. The positive and negative predictive values of having at least one
      secondary sign were 17.3% and 92%, respectively. CONCLUSION: These data suggest
      that the absence of secondary signs has a strong negative predictive value for
      appendicitis in the community hospital setting; however, the full utility of
      secondary signs may be limited in this setting.

PMID- 30293148
TI  - The most recent concepts for the management of bacterial and fungal infections in
      ICU.

PMID- 30293140
TI  - Postoperative ileus concealing intra-abdominal complications in enhanced recovery
      programs-a retrospective analysis of the GRACE database.
AB  - PURPOSE: Postoperative ileus (POI) occurrence within enhanced recovery programs
      (ERPs) has decreased. Also, intra-abdominal complications (IAC) such as
      anastomotic leakage (AL) generally present late. The aim was to characterize the
      link between POI and the other complications occurring after surgery. METHODS:
      This retrospective analysis of a prospective database was conducted by the
      Francophone Group for Enhanced Recovery after Surgery. POI was considered to be
      present if gastrointestinal functions had not been recovered within 3 days
      following surgery or if a nasogastric tube replacement was required. RESULTS: Of
      the 2773 patients who took part in the study, 2335 underwent colorectal
      resections (83.8%) for cancer, benign tumors, inflammatory bowel disease, and
      diverticulosis. Among the 2335 patients, 309 (13.2%) experienced POI, including
      185 (59.9%) cases of secondary POI. Adjusted for well-known risk factors (male
      gender, need for stoma, right hemicolectomy, surgery duration, laparotomy, and
      conversion to open surgery), POI was associated with abdominal complications (OR
      = 4.55; 95% confidence interval (CI): 3.30-6.28), urinary retention (OR = 1.75;
      95% CI: 1.05-2.92), pulmonary complications (OR = 4.55; 95% CI: 2.04-9.97), and
      cardiological complications (OR = 3.01; 95% CI: 1.15-8.02). Among the abdominal
      complications, AL and IAC were most strongly associated with POI (respectively,
      OR = 5.97; 95% CI: 3.74-8.88 and OR = 5.76; 95% CI: 3.56-10.62). CONCLUSION:
      Within ERPs, POI should not be considered as usual. There is a significant link
      between POI and IAC. Since POI is an early-onset clinical sign, its occurrence
      should alert the physician and prompt them to consider performing CT scans in
      order to investigate other potential morbidities.

PMID- 30293147
TI  - Use of Physical Activity Monitors in Rheumatic Populations.
AB  - PURPOSE OF REVIEW: The purpose of this review paper is to provide an overview of
      the recent research using physical activity monitors in rheumatic populations
      including those with osteoarthritis, rheumatoid arthritis, systemic lupus
      erythematosus, and fibromyalgia. RECENT FINDINGS: Recent research demonstrates
      increased use of physical activity monitors in these populations, especially in
      those with osteoarthritis. Results from cross-sectional, longitudinal, and
      intervention studies highlight that physical activity levels are below
      recommended guidelines, yet evidence suggests benefits such as improving pain,
      fatigue, function, and overall well-being. While the use of physical activity
      monitors in rheumatic populations is increasing, more research is needed to
      better understand physical activity levels in these populations, the effects of
      activity on relevant clinical outcomes, and how monitors can be used to help more
      individuals reach physical activity guidelines.

PMID- 30293149
TI  - "Familial venoms": a thallium intoxication cluster.

PMID- 30293150
TI  - Identification and characterization of the 4-epimerase AglW from the archaeon
      Methanococcus maripaludis.
AB  - Archaea are ubiquitous single-cell microorganisms that have often adapted to
      harsh conditions and play important roles in biogeochemical cycles with potential
      applications in biotechnology. Methanococcus maripaludis, a methane-producing
      archaeon, is motile through multiple archaella on its cell surface. The major
      structural proteins (archaellins) of the archaellum are glycoproteins, modified
      with N-linked tetrasaccharides that are essential for the proper assembly and
      function of archaella. The aglW gene, encoding the putative 4-epimerase AglW,
      plays a key role in the synthesis of the tetrasaccharide. The goal of our work
      was to biochemically demonstrate the 4-epimerase activity of AglW, and to develop
      assays to determine its substrate specificity and properties. We carried out
      assays using UDP-Galactose, UDP-Glucose, UDP-N-acetylglucosamine, UDP-N
      acetylgalactosamine and N-acetylglucosamine/N-acetylgalactosamine-diphosphate -
      lipid as substrates, coupled with specific glycosyltransferases. We showed that
      AglW has a broad specificity towards UDP-sugars and that Tyr151 within a
      conserved YxxxK sequon is essential for the 4-epimerase function of AglW. The
      glycosyltransferase-coupled assays are generally useful for the identification
      and specificity studies of novel 4-epimerases.

PMID- 30293151
TI  - Propiconazole is an activator of AHR and causes concentration additive effects
      with an established AHR ligand.
AB  - Consumers are exposed to pesticide residues and other food contaminants via the
      diet. Both can exert adverse effects on different target organs via the
      activation of nuclear receptor pathways. Hepatotoxic effects of the widely used
      triazole fungicide propiconazole (Pi) are generally attributed to the activation
      of the constitutive androstane receptor (CAR) or the pregnane X receptor (PXR).
      We now investigated the effects of Pi on the aryl hydrocarbon receptor (AHR) and
      possible mixture toxicity when Pi is present in combination with BbF, an AHR
      ligand. In silico docking simulations indicate that Pi can bind to human AHR.
      Subsequent dual luciferase reporter gene assays in human HepG2 cells showed that
      Pi activates the AHR in vitro. This concentration-dependent activation was
      confirmed by real-time RT-PCR analyses of the model AHR target genes CYP1A1 and
      CYP1A2 in human HepaRG and HepG2 cells. In addition, induction of CYP1A1 protein
      levels and enzyme activity were recorded. Similarly, increased mRNA expression
      and enzyme activity of Cyp1a1 and Cyp1a2 was observed in livers of rats treated
      with Pi for 28 days via the diet. Gene expression analysis in AHR-knockout HepaRG
      cells showed no induction of CYP1A1 and CYP1A2, whereas gene expression in CAR-,
      and PXR-knockout cells was induced. Finally, mixture effects of Pi and BbF were
      analyzed in human cell lines: modeling of concentration-response curves revealed
      concentration additivity. In conclusion, our results demonstrate that the
      triazole Pi is an activator of AHR in silico, in vitro and in vivo and causes
      additive effects with an established AHR ligand.

PMID- 30293152
TI  - Detection of Babesia gibsoni in dogs by combining recombinase polymerase
      amplification (RPA) with lateral flow (LF) dipstick.
AB  - Babesia gibsoni is a protozoan parasite responsible for the majority of reported
      cases of canine babesiosis in China. Currently, microscopic examination of the
      Giemsa-stained thin blood smears is the main diagnosis method in clinic. Here, we
      report the recombinase polymerase amplification-lateral flow (LF-RPA) dipstick
      detection method for targeting B. gibsoni cytochrome c oxidase subunit I (cox I)
      gene. The reaction takes only 20-30 min under isothermal temperatures between 30
      and 45  degrees C. Specificity was evaluated using DNA from related apicomplexan
      parasites and their host, while the sensitivity was calculated based on the DNA
      from the experimental B. gibsoni-infected dogs. Results indicated that the LF-RPA
      method is 20 times more sensitive than the conventional PCR based on 18S rRNA and
      has no cross reaction with any other test DNAs. The applicability of the LF-RPA
      method was further evaluated using 15 samples collected from clinic. Thirteen of
      the 15 samples (86.67%) were detected as positive by LF-RPA, while 10 of them
      (66.67%) were found positive by conventional PCR. Overall, the novel LF-RPA assay
      is effective for the detection of B. gobsini and has considerable advantages over
      the conventional PCR in sensitivity, specificity, simplicity in operation, less
      time consumption, and visual detection. The LF-RPA method may facilitate the
      surveillance and early detection of B. gibsoni infection in dogs.

PMID- 30293154
TI  - I have back pain!

PMID- 30293153
TI  - Incorporating EBO-HSIC with SVM for Gene Selection Associated with Cervical
      Cancer Classification.
AB  - Microarray technology is utilized by the biologists, in order to compute the
      expression levels of thousands of genes. Cervical cancer classification utilizing
      gene expression data depends upon conventional supervised learning methods,
      wherein only labeled data could be used for learning. The previous methodologies
      had problem with appropriate feature selection as well as accurateness of
      classification outcomes. So, the entire performance of the cancer classification
      is decreased meaningfully. With the aim of overcoming the aforesaid problems,
      Enhanced Bat Optimization Algorithm with Hilbert-Schmidt Independence Criterion
      (EBO-HSIC) and Support Vector Machine (SVM) algorithm is presented in this
      research for identifying the specific genes from the gene expression dataset that
      belongs to cancer microarray. This proposed system contains phases of instance
      normalization, module detection, gene selection and classification. By Fuzzy C
      Means (FCM) algorithm, the normalization is performed for eliminating the
      inappropriate features from the gene dataset. Meanwhile, for effective feature
      selection, the EBO algorithm is used for producing more appropriate features via
      improved objective function values. For determining a subset of the most
      informative genes utilizing a rapid as well as scalable bat algorithm, this
      proposed method focuses on measuring the dependence amid Differentially Expressed
      Genes (DEGs) as well as the gene significance. The algorithm is dependent upon
      the HSIC and was partially enthused by EBO. With the help of SVM classifier,
      these gene features are categorized very precisely. Experimentation outcomes
      demonstrate that the presented EBO with SVM algorithm confirms a clear-cut
      classification performance for the given gene expression datasets. Hence the
      result provides higher performance by launching EBO with SVM algorithm to obtain
      greater accuracy, recall, precision, f-measure and less time complexity more
      willingly than the previous techniques.

PMID- 30293156
TI  - Protracted febrile myalgia as a challenging manifestation of familial
      Mediterranean fever: case-based review.
AB  - Protracted febrile myalgia syndrome (PFMS) in familial Mediterranean fever (FMF)
      patients is a vasculitic condition characterized by severe myalgia, fever,
      abdominal pain, diarrhea, and arthralgia/arthritis episodes lasting 4-6 weeks.
      Symptoms typically resolve with corticosteroid treatment. However, in recent
      years, corticosteroid-resistant PFMS patients have been reported. We herein
      report five pediatric FMF patients complicated with PFMS. In addition,
      demographic findings, Mediterranean fever (MEFV) gene analysis, symptoms at
      disease onset, time interval between the diagnoses of FMF and PFMS, co-existent
      diseases, and treatment responses were evaluated. Resolution of all PFMS symptoms
      was accepted as complete response, while decreased symptoms without full recovery
      as partial response. We searched PubMed using the keywords 'protracted febrile
      myalgia' and 'anakinra', and reviewed the literature. There were three male and
      two female patients. Median age at the diagnosis of FMF was 6 (3-10) years. The
      time from diagnosis of FMF to the development of PFMS was changed from 0 to 8
      (median: 2) years. All of the patients, except one, had homozygous M694V
      mutation. All patients were treated with corticosteroids and non-steroidal anti
      inflammatory drugs (NSAIDs) first. Two out of five patients were exhibited
      partial response, while others exhibited complete response. Patients with partial
      response to the conventional therapies were treated with anakinra, and achieved a
      great response after the first dose. Anti-interleukin-1 (IL-1) therapy may be a
      beneficial and a reasonable treatment option, when there is insufficient response
      to NSAID and corticosteroid therapies in pediatric PFMS patients.

PMID- 30293155
TI  - Discordance of global assessment by patients and physicians is higher in
      osteoarthritis than in rheumatoid arthritis: a cross-sectional study from routine
      care.
AB  - The study compares patient-physician discordance in global assessment in patients
      with osteoarthritis (OA) versus patients with rheumatoid arthritis (RA) seen in
      routine care. This is a cross-sectional study conducted at an academic
      rheumatology center at which all patients are asked to complete a Multi
      Dimensional Health Assessment Questionnaire (MDHAQ), which includes a patient
      global assessment (PATGL). Rheumatologists are encouraged to complete a physician
      questionnaire, which includes a physician global assessment (DOCGL). Patients
      with either OA or RA were identified using ICD9 codes and classified as positive
      discordance (PATGL-DOCGL >= 2), negative discordance (PATGL-DOCGL<= - 2), and
      concordance (absolute difference between the two assessments < 2). Discordance
      was assessed by diagnosis. Agreement between patient and physician global
      assessments was evaluated using intraclass correlations. Logistic regression was
      performed to identify explanatory variables for positive discordance. The
      analysis included 243 OA and 216 RA patients. Mean PATGL was higher in OA versus
      RA (5.4 versus 4.2, p = 0.005), while mean DOCGL was similar (4.0 versus 3.8, p =
      0.23) leading to a higher patient-physician discordance in OA (1.35 versus 0.43,
      p < 0.001). Positive discordance occurred in 34% of OA versus 18% of RA patients
      (p < 0.001). Intraclass correlation coefficients were 0.43 in OA versus 0.60 in
      RA patients. In logistic regressions, pain was the only statistically significant
      explanatory variable for discordance in both OA (OR 1.34, 95% CI 1.12-1.78) and
      RA (OR 1.47 95% CI 1.04-2.07). Patients with OA are more likely to be discordant
      with their rheumatologists than patients with RA because of a higher PATGL.
      Similarly to RA, the most important explanatory variable for discordance was
      higher pain.

PMID- 30293157
TI  - Etanercept-induced Crohn's disease in ankylosing spondylitis: a case report and
      review of the literature.
AB  - Tumor necrosis factor (TNF)-alpha is a cytokine that plays a well-established,
      key role as a central mediator of inflammation and immune regulation. TNF-alpha
      and its receptors are suggested to play a critical role in a number of chronic
      inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis,
      ankylosing spondylitis (AS), juvenile chronic arthritis, and inflammatory bowel
      disease (IBD). TNF-alpha inhibitors are currently used in the treatment of these
      diseases. We report a 29-year-old male with AS who developed Crohn's disease
      while taking etanercept. Etanercept treatment was interrupted and a switch to a
      monoclonal antibody-based anti-TNF treatment using adalimumab was started, which
      induced a prompt improvement of the gastrointestinal symptoms. We indicate the
      immunodysregulatory and proinflammatory effects of etanercept and discuss the
      potential pathogenic mechanisms of the paradoxical effect of TNF-alpha
      inhibitors. We also review the related literature on new-onset IBD following anti
      TNF treatment for AS.

PMID- 30293158
TI  - Spinal cord stimulation modulates descending pain inhibition and temporal
      summation of pricking pain in patients with neuropathic pain.
AB  - BACKGROUND: Spinal cord stimulation (SCS) is an established treatment option for
      patients with refractory chronic pain conditions. While effects of SCS on dorsal
      horn neuronal circuitries are intensively studied, current knowledge on the
      impact of SCS on descending pain pathways is scarce and relies on preclinical
      data. We aimed to address this topic and hypothesized a significant effect of SCS
      on descending pain modulation. In light of current efforts to determine the
      sensitivity of "static" versus "dynamic" somatosensory parameters to characterize
      pathophysiological pain conditions, all SCS patients were carefully investigated
      using both classes of somatosensory outcome parameters. METHODS: Descending pain
      pathways were investigated by using a "Cold Pressor Test." This test enables to
      evaluate the efficacy of conditioned pain modulation (CPM) at the individual
      level. CPM efficacy was assessed in eight neuropathic pain patients (age 55.5 +/-
      10.6) during the two conditions stimulator "ON" and "OFF." The impact of SCS on
      "static" and "dynamic" somatosensory parameters was explored by using a
      quantitative sensory testing (QST) battery. RESULTS: CPM efficacy on pressure
      pain sensitivity was nearly absent during "OFF" (- 1.2 +/- 5.6% facilitation),
      but increased significantly to 16.3 +/- 3.4% inhibition during "ON" (p = 0.03).
      While most "static" nociceptive QST parameters, represented by mechanical/thermal
      pain thresholds, exhibited only small effects of SCS (p > 0.05), the wind-up
      ratio was strongly reduced to within the normal range during "ON" (p = 0.04;
      Cohen's d = 1.0). Dynamic mechanical allodynia was abolished in six of seven
      patients. CONCLUSIONS: Our study provides first human evidence for an impact of
      SCS on descending pain pathways in the dorsolateral funiculus and emphasizes the
      significance of "dynamic" pain measures like "CPM"-efficacy and "temporal
      summation" to evaluate SCS treatment effects. Future prospective studies may use
      these measures of nociceptive processing to predict SCS therapy response.

PMID- 30293159
TI  - Correction to: Reassessing Coronary Artery Bypass Surgery Versus Percutaneous
      Coronary Intervention in Patients with Type 2 Diabetes Mellitus: A Brief Updated
      Analytical Report (2015-2017).
AB  - In the original publication, conclusion was incorrectly updated in the article
      main text. The complete statement is given below.

PMID- 30293161
TI  - Interactions between polycyclic aromatic hydrocarbons and epoxide hydrolase 1
      play roles in asthma.
AB  - Asthma, as one of the most common chronic diseases in children and adults, is a
      consequence of complex gene-environment interactions. Polycyclic aromatic
      hydrocarbons (PAHs), as a group of widespread environmental organic pollutants,
      are involved in the development, triggering and pathologic changes of asthma.
      Various previous studies reported the critical roles of PAHs in immune changes,
      oxidative stress and environment-gene interactions of asthma. EPHX1 (the gene of
      epoxide hydrolase 1, an enzyme mediating human PAH metabolism) had a possible
      association with asthma by influencing PAH metabolism. This review summarized
      that (1) the roles of PAHs in asthma-work as risk factors; (2) the possible
      mechanisms involved in PAH-related asthma-through immunologic and oxidative
      stress changes; (3) the interactions between PAHs and EPHX1 involved in asthma
      enzymatic activity of epoxide hydrolase 1, which affected by EPHX1
      genotypes/SNPs/diplotypes, could influence human PAH metabolism and people's
      vulnerability to PAH exposure. This review provided a better understanding of the
      above interactions and underlying mechanisms for asthma which help to raise
      public's concern on PAH control and develop strategies for individual asthma
      primary prevention.

PMID- 30293160
TI  - Wearable Sensors to Monitor, Enable Feedback, and Measure Outcomes of Activity
      and Practice.
AB  - PURPOSE OF REVIEW: Measurements obtained during real-world activity by wearable
      motion sensors may contribute more naturalistic accounts of clinically meaningful
      changes in impairment, activity, and participation during neurologic
      rehabilitation, but obstacles persist. Here we review the basics of wearable
      sensors, the use of existing systems for neurological and rehabilitation
      applications and their limitations, and strategies for future use. RECENT
      FINDINGS: Commercial activity-recognition software and wearable motion sensors
      for community monitoring primarily calculate steps and sedentary time. Accuracy
      declines as walking speed slows below 0.8 m/s, less so if worn on the foot or
      ankle. Upper-extremity sensing is mostly limited to simple inertial activity
      counts. Research software and activity-recognition algorithms are beginning to
      provide ground truth about gait cycle variables and reveal purposeful arm
      actions. Increasingly, clinicians can incorporate inertial and other motion
      signals to monitor exercise, activities of daily living, and the practice of
      specific skills, as well as provide tailored feedback to encourage self
      management of rehabilitation. Efforts are growing to create a compatible
      collection of clinically relevant sensor applications that capture the type,
      quantity, and quality of everyday activity and practice in known contexts. Such
      data would offer more ecologically sound measurement tools, while enabling
      clinicians to monitor and support remote physical therapies and behavioral
      modification when combined with telemedicine outreach.

PMID- 30293162
TI  - Cranioplasty following decompressive craniectomy: minor surgical complexity but
      still high periprocedural complication rates.
AB  - Cranioplasty following decompressive craniectomy is of low surgical complexity,
      so much so that it has become the "beginners" cranial case. However, these
      "simple" procedures may have high complication rates. Identification of specific
      risk factors would allow targeted intervention to lower the complication rates.
      The aim of this study was to assess the rate of complications and to evaluate
      potential risk factors. We conducted a review of all patients who underwent
      cranioplasty in our center following decompressive craniectomy for stroke or
      brain trauma between 2009 and 2016. One hundred fifty-two patients were
      identified. Fifty-three percent were male. Mean age was 48 (range 11-78). Median
      time from craniectomy until cranioplasty was 102 days (range 14-378). The overall
      rate of complications, such as postoperative bleeding, seizures, postoperative
      infection, and hydrocephalus, was 30%. The mortality rate was 1%. None of the
      following potential risk factors was associated with significantly increased risk
      of periprocedural complications: gender (p = 0.34), age (p = 0.39), cause of
      initial surgery (p = 0.08), duration of surgery (p = 0.59), time of surgery
      (0.24), surgical experience (p = 0.17), and time from craniectomy until
      cranioplasty (p = 0.27). The 30-day complication rate following cranioplasty is
      high, but serious permanent deficits from these complications were rare. We found
      no clear predictor for these 30-day complications, which renders its prevention
      difficult.

PMID- 30293164
TI  - Letter to the editor relating to Graefe's Arch Clin Exp Ophthalmol. 2018 May;
      256(5): 863-877. "Macular buckle technique in myopic traction maculopathy: a 16
      year review of the literature and a comparison with vitreous surgery".

PMID- 30293163
TI  - Risk factors for post-thrombotic syndrome in patients with deep vein thrombosis:
      from the COMMAND VTE registry.
AB  - Post-thrombotic syndrome (PTS) is the most common chronic complication of deep
      vein thrombosis (DVT). Identifying high-risk patients for the development of PTS
      might be useful for its prevention. The COMMAND VTE Registry is a multicenter
      registry that enrolled 3027 consecutive patients with acute symptomatic venous
      thromboembolisms (VTEs) in Japan between January 2010 and August 2014. The
      current study population consisted of 1298 patients with lower extremities DVTs
      who completed 3-year follow-up for those who developed PTS and those without PTS.
      We investigated risk factors for the development of PTS at the time of DVT
      diagnosis, using a multivariable logistic regression analysis. Of the entire 1298
      study patients, 169 (13%) patients were diagnosed with PTS within 3 years. The
      rate for anticoagulation discontinuation during follow-up was not significantly
      different between those with and without PTS. Chronic kidney disease (OR 2.21,
      95% CI 1.45-3.39, P < 0.001), leg swelling (OR 4.15, 95% CI 2.25-7.66, P <
      0.001), absence of transient risk factors for VTEs (OR 2.39, 95% CI 1.55-3.67, P
      < 0.001), active cancer (OR 3.66, 95% CI 2.30-5.84, P < 0.001), and thrombophilia
      (OR 2.07, 95% CI 1.06-4.04, P = 0.03) were independent risk factors for the
      development of PTS. In this real-world Japanese DVT registry, we could identify
      several important risk factors for the development of PTS at the time of DVT
      diagnosis.

PMID- 30293165
TI  - The potential role of folate metabolism in interstitial cystitis.
AB  - The topic of interstitial cystitis (IC), also known as painful bladder syndrome
      (PBS), and folate/one carbon metabolism has previously been unaddressed in
      research. This narrative review highlights a potential connection for those with
      mast cell-related IC and histamine-mediated pain that is explored through four
      conceptual sections. The first section focuses on the nature of mast cell
      involvement and histamine-mediated pain in some interstitial cystitis patients.
      The second section reviews the literature on folate status in wider allergic
      conditions. The third section addresses the role of folate and methylation in
      general in histamine excretion. Finally, folate metabolism and vascular function
      are addressed because of the vascular abnormalities present in some IC bladders.

PMID- 30293166
TI  - A randomized controlled trial comparing two voiding trials after midurethral
      sling with or without colporrhaphy.
AB  - INTRODUCTION AND HYPOTHESIS: To compare the force of the stream (FOS) voiding
      trial with the standard voiding trial (SVT) after outpatient midurethral sling
      (MUS) whether or not colporrhaphy was performed. METHODS: This is a randomized
      controlled non-inferiority trial of patients scheduled for MUS or colporrhaphy.
      Sample size of 102 patients was calculated for 80% power. Patients were
      randomized to FOS or SVT. Primary outcome was the number of unexpected
      postoperative visits (UPOVs) for voiding dysfunction (VD) or urinary tract
      infection (UTI). Voiding dysfunction was defined as urinary retention or post
      void residual (PVR) > 200 cc. Subjects rated FOS using a visual analog scale
      (VAS). Criterion for non-inferiority was an upper limit of < 10% for the 95% CI.
      Analyses were performed using SAS version 9.4 (SAS Institute. Cary, NC). RESULTS:
      One hundred two subjects were included (49 FOS, 53 SVT). Immediate postoperative
      catheterization for FOS and SVT was 8.2% (n = 4) and 9.4% (n = 5), respectively.
      Recovery time was significantly less for FOS versus SVT (p = 0.0002). Total UPOVs
      were five (10.2%) and two (3.8%) for FOS and SVT, respectively. Two FOS subjects
      who had MUS + colporrhaphy passed their VT and had subsequent UPOVs for VD. No
      evidence of non-inferiority was noted when comparing FOS to SVT for total UPOVs:
      CI: 6.0% (-5.2, 17.2) for postoperative VD [CI: 6.1% (-4.0, 16.2)] or UTIs [CI:
      0.3% (-9.4, 10.1)]. CONCLUSIONS: No evidence of non-inferiority was noted
      comparing FOS with SVT for unexpected postoperative visits for voiding
      dysfunction or UTI. This study shows the need for larger studies to assess the
      use of the FOS method in patients undergoing surgery for prolapse with or without
      MUS.

PMID- 30293167
TI  - Risk of new-onset urinary incontinence 3 and 12 months after vaginal or cesarean
      delivery of twins: Part I.
AB  - INTRODUCTION AND HYPOTHESIS: Our purpose was to compare the prevalence of urinary
      incontinence (UI) 3 and 12 months after vaginal vs cesarean delivery of twins
      after 34 weeks of gestation. METHODS: This was a multicenter prospective cohort
      study conducted at 172 French maternity units and included 2812 primiparous women
      with twins with no prior history of UI. Participants were enrolled at the time of
      delivery and followed up to 12 months postpartum. The primary outcome was the
      prevalence of UI, both stress and urge, 3 months postpartum, based on the patient
      reporting any frequency of urine leakage to the first question of the
      International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF).
      The Pelvic Floor Distress Inventory - Short Form 20 (PFDI-20), Pelvic Floor
      Impact Questionnaire - Short Form 7 (PFIQ-7), Pelvic Organ Prolapse/Urinary
      Incontinence Sexual Questionnaire (PISQ-12), and Medical Outcome Study Short Form
      12 (SF-12) were also used. RESULTS: The ICIQ-SF was completed by 1155 (39.8%) and
      800 (27.5%) women, respectively, at 3 and 12 months postpartum; 556 (48%) had
      delivered vaginally and 599 (52%) by cesarean section. The prevalence of UI at 3
      months was 26% overall and was significantly higher in the vaginal delivery group
      at both 3 months (35% vs 17% in the cesarean group, p < 0.0001) and 12 months
      postpartum (38% vs 24%, p < 0.0001). UI was predominantly stress or mixed. The
      risk factors for UI at 3 months, determined by multivariate modeling, were
      vaginal delivery [odds ratio (OR) 3.073, 95% confidence interval (CI) 2.3-4.105,
      p < 0.0001) and body mass index >25 in early pregnancy (OR 1.620, 95% CI 1.188
      2.209, p = 0.0023). CONCLUSIONS: Vaginal delivery is a risk factor for UI at 3
      months after twin birth.

PMID- 30293168
TI  - Complete labial fusion in a postmenopausal woman: unusual cause of urinary
      symptoms.

PMID- 30293169
TI  - Physiological response of crossbred sheep under nutritional scarcity.
AB  - Nutritional scarcity during summer and winter is a major constraint for sheep
      rearing in the semi-arid tropical region. In this region, a new crossbred sheep
      has been developed by the crossing of a native sheep breed Malpura with a breed
      of hot-humid coastal region breed Garole. A study was conducted for 9 weeks to
      assess the physiological response of crossbred (Garole x Malpura x Malpura, GMM)
      rams under nutritional scarcity in the semi-arid tropical region. Eighteen adult
      crossbred rams were randomly allocated into three groups of six animals each. The
      groups are G1 (control, ad libitum feeding), G2 (20% less than ad libitum
      feeding), and G3 (30% less than ad libitum feeding). The animals were stall-fed
      with a diet consisting of 70% roughage (Cenchrus ciliaris hay) and 30%
      concentrate feed. Body weight gain, average daily gain, and feed intake were
      significantly (P < 0.05) lower in G2 and G3 as compared to G1 rams. Water intake
      was significantly (P < 0.05) higher in G2 and G3. Physiological responses, blood
      biochemical and endocrine profile did not differ between the groups. The results
      indicate that the crossbred rams evolved through the crossing of the hot semi
      arid tropical region breed with hot humid coastal region breed are able to
      maintain their body homeostasis despite nutritional scarcity although their body
      weight decreased.

PMID- 30293170
TI  - Velocity Curvature Index: a Novel Diagnostic Biomarker for Large Vessel
      Occlusion.
AB  - Despite being a conveniently portable technology for stroke assessment,
      Transcranial Doppler ultrasound (TCD) remains widely underutilized due to complex
      training requirements necessary to reliably obtain and interpret cerebral blood
      flow velocity (CBFV) waveforms. The validation of objective TCD metrics for large
      vessel occlusion (LVO) represents a first critical step toward enabling use by
      less formally trained personnel. In this work, we assess the diagnostic utility,
      relative to current standard CT angiography (CTA), of a novel TCD-derived
      biomarker for detecting LVO. Patients admitted to the hospital with stroke
      symptoms underwent TCD screening and were grouped into LVO and control groups
      based on the presence of CTA confirmed occlusion. Velocity curvature index (VCI)
      was computed from CBFV waveforms recorded at multiple depths from the middle
      cerebral arteries (MCA) of both cerebral hemispheres. VCI was assessed for 66
      patients, 33 of which had occlusions of the MCA or internal carotid artery. Our
      results show that VCI was more informative when measured from the cerebral
      hemisphere ipsilateral to the site of occlusion relative to contralateral.
      Moreover, given any pair of bilateral recordings, VCI separated LVO patients from
      controls with average area under receiver operating characteristic curve of 92%,
      which improved to greater than 94% when pairs were selected by maximal velocity.
      We conclude that VCI is an analytically valid candidate biomarker for LVO
      diagnosis, possessing comparable accuracy, and several important advantages,
      relative to current TCD diagnostic methodologies.

PMID- 30293172
TI  - Tactile sensor-based real-time clustering for tissue differentiation.
AB  - PURPOSE: Reliable intraoperative delineation of tumor from healthy brain tissue
      is essentially based on the neurosurgeon's visual aspect and tactile impression
      of the considered tissue, which is-due to inherent low brain consistency contrast
      a challenging task. Development of an intelligent artificial intraoperative
      tactile perception will be a relevant task to improve the safety during surgery,
      especially when-as for neuroendoscopy-tactile perception will be damped or-as for
      surgical robotic applications-will not be a priori existent. Here, we present the
      enhancements and the evaluation of a tactile sensor based on the use of a
      piezoelectric tactile sensor. METHODS: A robotic-driven piezoelectric bimorph
      sensor was excited using multisine to obtain the frequency response function of
      the contact between the sensor and fresh ex vivo porcine tissue probes. Based on
      load-depth, relaxation and creep response tests, viscoelastic parameters E1 and
      E2 for the elastic moduli and eta for the viscosity coefficient have been
      obtained allowing tissue classification. Data analysis was performed by a
      multivariate cluster algorithm. RESULTS: Cluster algorithm assigned five clusters
      for the assignment of white matter, basal ganglia and thalamus probes. Basal
      ganglia and white matter have been assigned to a common cluster, revealing a less
      discriminatory power for these tissue types, whereas thalamus was exclusively
      delineated; gray matter could even be separated in subclusters. CONCLUSIONS:
      Bimorph-based, multisine-excited tactile sensors reveal a high sensitivity in ex
      vivo tissue-type differentiation. Although, the sensor principle has to be
      further evaluated, these data are promising.

PMID- 30293171
TI  - Measuring relative vibrotactile spatial acuity: effects of tactor type, anchor
      points and tactile anisotropy.
AB  - Vibrotactile displays can compensate for the loss of sensory function of people
      with permanent or temporary deficiencies in vision, hearing, or balance, and can
      augment the immersive experience in virtual environments for entertainment, or
      professional training. This wide range of potential applications highlights the
      need for research on the basic psychophysics of mechanisms underlying human
      vibrotactile perception. One key consideration when designing tactile displays is
      determining the minimal possible spacing between tactile motors (tactors), by
      empirically assessing the maximal throughput of the skin, or, in other words,
      vibrotactile spatial acuity. Notably, such estimates may vary by tactor type. We
      assessed vibrotactile spatial acuity in the lower thoracic region for three
      different tactor types, each mounted in a 4 * 4 array with center-to-center inter
      tactor distances of 25 mm, 20 mm, and 10 mm. Seventeen participants performed a
      relative three-alternative forced-choice point localization task with successive
      tactor activation for both vertical and horizontal stimulus presentation. The
      results demonstrate that specific tactor characteristics (frequency,
      acceleration, contact area) significantly affect spatial acuity measurements,
      highlighting that the results of spatial acuity measurements may only apply to
      the specific tactors tested. Furthermore, our results reveal an anisotropy in
      vibrotactile perception, with higher spatial acuity for horizontal than for
      vertical stimulus presentation. The findings allow better understanding of
      vibrotactile spatial acuity and can be used for formulating guidelines for the
      design of tactile displays, such as regarding inter-tactor spacing, choice of
      tactor type, and direction of stimulus presentation.

PMID- 30293173
TI  - Virtual downsizing for decision support in mitral valve repair.
AB  - PURPOSE: Various options are available for the treatment of mitral valve
      insufficiency, including reconstructive approaches such as annulus correction
      through ring implants. The correct choice of general therapy and implant is
      relevant for an optimal outcome. Additional to guidelines, decision support
      systems (DSS) can provide decision aid by means of virtual intervention planning
      and predictive simulations. Our approach on virtual downsizing is one of the
      virtual intervention tools that are part of the DSS workflow. It allows for
      emulating a ring implantation based on patient-specific lumen geometry and vendor
      specific implants. METHODS: Our approach is fully automatic and relies on a lumen
      mask and an annulus contour as inputs. Both are acquired from previous DSS
      workflow steps. A virtual surface- and contour-based model of a vendor-specific
      ring design (26-40 mm) is generated. For each case, the ring geometry is
      positioned with respect to the original, patient-specific annulus and additional
      anatomical landmarks. The lumen mesh is parameterized to allow for a vertex-based
      deformation with respect to the user-defined annulus. Derived from post
      interventional observations, specific deformation schemes are applied to atrium
      and ventricle and the lumen mesh is altered with respect to the ring location.
      RESULTS: For quantitative evaluation, the surface distance between the deformed
      lumen mesh and segmented post-operative echo lumen close to the annulus was
      computed for 11 datasets. The results indicate a good agreement. An arbitrary
      subset of six datasets was used for a qualitative evaluation of the complete
      lumen. Two domain experts compared the deformed lumen mesh with post
      interventional echo images. All deformations were deemed plausible. CONCLUSION:
      Our approach on virtual downsizing allows for an automatic creation of plausible
      lumen deformations. As it takes only a few seconds to generate results, it can be
      added to a virtual intervention toolset without unnecessarily increasing the
      pipeline complexity.

PMID- 30293174
TI  - Reducing carbapenem prescribing in high-use settings: it is possible, and it is
      good to talk.

PMID- 30293175
TI  - Fluorometric determination of doxycycline based on the use of carbon quantum dots
      incorporated into a molecularly imprinted polymer.
AB  - A fluorometric assay is described for doxycycline detection. It is based on the
      use of nitrogen-doped carbon quantum dots (NCQDs) coated with molecularly
      imprinted polymers (MIPs). The NCQDs were prepared by a one-step hydrothermal
      reaction using citric acid and ethylenediamine (EDA) as the starting materials.
      Afterwards, the NCQDs were incorporated into the polymer that was molecularly
      imprinted with doxycycline. It is found that doxycycline quenches the
      fluorescence of the NCQDs, and that the functional groups on the surface of NCQDs
      play an important role in terms of quenching efficiency. A larger fraction of
      carboxyl groups presented on the surface of NCQDs leads to a higher quenching
      efficiency due to the enhanced electron transfer from NCQD to doxycycline. The
      NCQDs@MIP composite can specifically and rapidly recognize doxycycline.
      Fluorescence drops linearly in the 5 to 50 MUM doxycycline concentration range,
      and the limit of detection is 87 nM. This method was successfully applied to the
      determination of doxycycline in spiked pig serum where it gave recovery rates of
      >94%. Graphical abstract Schematic illustration for fabricating a fluorescent
      sensor based on nitrogen-doped carbon quantum dots (NCQDs) and molecularly
      imprinted polymers (MIPs). The sensor integrates the merits of the high
      sensitivity of NCQD and good selectivity of MIPs, and can be significantly
      quenched upon interaction with doxycycline.

PMID- 30293176
TI  - Quality not quantity: loneliness subtypes, psychological trauma, and mental
      health in the US adult population.
AB  - PURPOSE: Loneliness is a recognised public-health concern that is traditionally
      regarded as a unidimensional construct. Theories of loneliness predict the
      existence of subtypes of loneliness. In this study, latent class analysis (LCA)
      was used to test for the presence of loneliness subtypes and to examine their
      association with multiple mental health variables. METHODS: A nationally
      representative sample of US adults (N = 1839) completed the De Jong Gierveld
      Loneliness Scale, along with self-report measures of childhood and adulthood
      trauma, psychological wellbeing, major depression, and generalized anxiety.
      RESULTS: When treated as a unidimensional construct, 17.1% of US adults aged 18
      70 were classified as lonely. However, the LCA results identified four loneliness
      classes which varied quantitatively and qualitatively: 'low' (52.8%), 'social'
      (8.2%), 'emotional' (26.6%), and 'social and emotional' (12.4%) loneliness. The
      'social and emotional' class were characterised by the highest levels of
      psychological distress, followed by the 'emotional' class. The 'social'
      loneliness class had similar mental health scores as the 'low' loneliness class.
      Childhood and adulthood trauma were independently related to the most distressed
      loneliness classes. CONCLUSIONS: Current findings provide support for the
      presence of subtypes of loneliness and show that they have unique associations
      with mental health status. Recognition of these subtypes of loneliness revealed
      that the number of US adults aged 18-70 experiencing loneliness was twice as high
      as what was estimated when loneliness was conceptualized as a unidimensional
      construct. The perceived quality, not the quantity, of interpersonal connections
      was associated with poor mental health.

PMID- 30293177
TI  - Mulching with coffee husk and pulp in strawberry affects edaphic predatory mite
      and spider mite densities.
AB  - Mulching of soil beds of strawberry fields is usually done with polyethylene film
      in southern Minas Gerais state, Brazil. This material is relatively expensive and
      difficult to discard after use. In some countries, mulching is done with the use
      of organic material that could have an advantage over the use of plastic for its
      easier degradation after use, and for favoring edaphic beneficial organisms.
      Predatory mites (especially Gamasina, Mesostigmata) may be abundant in the soil
      and could conceivably move to the soil surface and onto the short-growing
      strawberry plants at night, helping in the control or pest arthropods. The two
      spotted spider mite, Tetranychus urticae Koch, is considered an important
      strawberry pest in that region, where the fungus Neozygites floridana (Weiser and
      Muma) has been found to infect it. Different mulching types could affect the
      incidence of this pathogen. Dehydrated coffee husk and pulp (DCHP) is a byproduct
      readily available in southern Minas Gerais, where could be used as organic
      mulching in strawberry beds. The temporary contact of that material with the soil
      of a patch of natural vegetation could facilitate its colonization by edaphic
      predatory mites helpful in the control of strawberry pests. The objective of this
      work was to study the effect of mulching type on the population dynamics of the
      two-spotted spider mite, associate mites and N. floridana, in a greenhouse and in
      the field. The use of DCHP increased the number of edaphic Gamasina on strawberry
      plants-Proctolaelaps pygmaeus (Muller) (Melicharidae) and Blattisocius
      dentriticus (Berlese) (Blattisociidae) were observed on strawberry leaflets,
      mainly in nocturnal samplings, indicating their possible daily migration from
      soil to plants. Lower levels of two-spotted spider mite occurred on plants from
      pots or soil beds mulched with DCHP instead of polyethylene film, possibly
      because of the slightly higher levels of mites of the family Phytoseiidae and
      infection by N. floridana. Adding DCHP onto the floor of natural vegetation did
      not result in higher diversity or levels of gamasine mites on DCHP. Complementary
      studies should be conducted to find ways to increase diversity and density of
      those organisms in strawberry beds, in an attempt to improve biological control
      of strawberry pests. The decision to use DCHP for mulching should also take into
      account other factors such as strawberry yield, costs and efficiency of weed
      management, to be evaluated in subsequent studies.

PMID- 30293178
TI  - Quantitative assessment of dietary supplement intake in 77,000 French adults:
      impact on nutritional intake inadequacy and excessive intake.
AB  - BACKGROUND: Dietary supplements (DS) are largely consumed in Western countries
      without demonstrating their nutritional benefits and safety in the general
      population. The aims, in a large population-based study of French adults, were:
      (1) to compare the prevalence of nutrient intake inadequacy and the proportion of
      individuals exceeding tolerable upper intake levels (UL) between DS users and non
      users, and (2) to quantify the extent of potentially "at-risk" DS use practices
      (e.g., DS/drugs contraindicated association or use of beta-carotene DS in
      smokers). METHODS: 76,925 participants, 47.6% men and 52.4% women, mean age 46.9
      +/- 16.3 years were enrolled to the NutriNet-Sante cohort and they completed a
      quantitative DS questionnaire and three 24 h dietary records. A composition
      database including > 8000 DS was developed. Variance reduction was applied to
      estimate usual intakes and analyses were weighted according to the French census
      data. RESULTS: Among DS users of the specific nutrient, DS contributed to 41% of
      total intake for vitamin D in men, 55% in women; and to 20% of total intake for
      pyridoxine in men, 21% in women. Compared to dietary intakes only, their
      prevalence of inadequacy was reduced by 11% for vitamin C, 9% for magnesium, 6%
      for pyridoxine in men, and 19% for calcium, 12% for iron, and 11% for magnesium
      in women (p < 0.0001). The proportion of subjects exceeding UL reached 6% for
      iron and 5% for magnesium in men, and 9% for iron in women. 6% of DS users had
      potentially "at-risk" practices. CONCLUSION: While DS use contributed to decrease
      the prevalence of insufficient intake for several nutrients, it also conveyed
      excessive intake of iron and magnesium. Besides, a substantial proportion of
      potentially "at-risk" DS use practices was reported.

PMID- 30293179
TI  - Association of exclusive breastfeeding duration with consumption of ultra
      processed foods, fruit and vegetables in Brazilian children.
AB  - BACKGROUND: There has been little evidence of the influence of breastfeeding on
      childhood eating habits. AIM: To evaluate the association between duration of
      exclusive breastfeeding (EB) and consumption of ultra-processed foods, fruits and
      vegetables by Brazilian children. METHODS: This is a cross-sectional study nested
      in a cohort of 403 children age 4-7 years. Food consumption was evaluated by
      three food records and the foods were grouped by the amount of processing
      involved (minimal, including fruit and vegetables to ultra-processed foods).
      Adjusted linear and multinomial regression models were proposed to evaluate the
      association of EB with children's food intake. Median duration of EB was 4.0 (2.0
      6.0) months and the prevalence of EB of 4 months or more was 60.9%. RESULTS: Mean
      energy consumption was 1536 kcal/day, 38% of energy was from ultra-processed
      foods. Mean intake of fruit and vegetables was 130 g/day. For each 1-month
      increase in duration of EB there was a 0.7% decrease in energy from ultra
      processed foods (beta: - 0.7; 95% CI: - 1.3 to 0.1; p = 0.038). EB of less than 4
      months was associated with the child being in the lowest tercile for consumption
      of fruit and vegetables (Adjusted OR: 1.8; 95% CI: 1.1-3.0; p = 0.030) and the
      highest for consumption of ultra-processed foods (adjusted OR: 1.7; 95% CI: 1.1
      2.9; p = 0.040). CONCLUSIONS: In addition to other benefits of EB, we emphasize
      its importance for the formation of healthy eating habits, contributing to a
      higher consumption of fruit and vegetables and lower consumption of ultra
      processed foods in childhood.

PMID- 30293180
TI  - Abnormal Functional Connectivity Density in Post-Stroke Aphasia.
AB  - Post-stroke aphasia (PSA), which refers to the loss or impairment of language, is
      typically caused by left hemisphere lesions. Previous neuroimaging studies have
      indicated that the pathology of PSA may be related to abnormalities in functional
      integration. In this study, we used resting-state functional magnetic resonance
      imaging (rs-fMRI) to examine functional connectivity density (FCD) in PSA. We
      compared short- and long-range FCD between individuals with PSA (n = 17) and
      healthy controls (HC, n = 20). We then performed Pearson's correlation analysis
      on the FCD values from the affected brain regions and the speech scores in the
      PSA group. Compared with HCs, individuals with PSA showed increased short-range
      FCD in the contralesional temporal gyrus, the inferior frontal gyrus, the
      thalamus, the insula, and the mesial temporal gyrus [hippocampus/parahippocampus
      (HIP/ParaHIP)]. PSA demonstrated an increased long-range FCD in the
      contralesional mesial temporal gyrus (HIP/ParaHIP). PSA also displayed decreased
      short-range FCD in the ipsilesional part of the frontal gyrus, the caudate, the
      thalamus, the fusiform gyrus, and the mesial temporal gyrus (HIP/ParaHIP), and
      decreased long-range FCD in the ipsilesional superior temporal gyrus, the
      fusiform gyrus, and the mesial temporal gyrus (HIP/ParaHIP). The decreased long
      range FCD in the left superior temporal gyrus in PSA subjects was positively
      correlated with the spontaneous speech score. The altered FCD observed due to
      disrupted functional connectivity after stroke may lead to language production,
      semantic processing, and cognitive impairments. Our findings expand previous
      functional studies on stroke and provide new evidence of the intraregional and
      interregional interactions at the voxel level in the pathophysiology of PSA.

PMID- 30293181
TI  - Greater knee flexion excursion/moment in hopping is associated with better knee
      function following anterior cruciate ligament reconstruction.
AB  - PURPOSE: Individuals with impaired knee function after anterior cruciate ligament
      reconstruction (ACLR) may be at greater risk of developing knee osteoarthritis
      related to abnormal knee joint movement and loading. The aim of this study was to
      assess the association between knee biomechanics and knee laxity during hopping
      and clinically assessed knee function (i.e., patient-reported knee function and
      hop tests) following ACLR. METHODS: Sixty-six participants (23 women, mean age 28
      +/- 6 years, mean 18 +/- 3 months following ACLR) completed a standardized single
      leg hopping task. Three-dimensional movement analysis was used to assess knee
      flexion excursion and body weight/height normalized knee flexion moments during
      landing for the involved limb. Anterior-posterior knee laxity was assessed with a
      KT-1000 knee arthrometer. Participants then completed a patient-reported knee
      function questionnaire and three separate hop tests (% of uninvolved limb) and
      were divided into poor and satisfactory knee function groups (satisfactory: >=85%
      patient-reported knee function and >= 85% hop test symmetry). Associations
      between knee function and hop biomechanics/knee laxity were assessed using
      logistic regression and interquartile range scaled odds ratios (ORIQR). RESULTS:
      Greater knee flexion excursion (ORIQR 2.9, 95%CI 1.1-7.8), greater knee flexion
      moment (ORIQR 4.9, 95%CI 1.6-14.3) and lesser knee laxity (ORIQR 4.7, 95%CI 1.5
      14.9) were significantly associated with greater odds of having satisfactory knee
      function (>= 85% patient-reported knee function and >= 85% hop test symmetry).
      CONCLUSION: Greater knee flexion excursion/moment during hop-landing and lesser
      knee laxity is associated with better patient-reported knee function and single
      leg hop test performance following ACLR. Patients with lower levels of knee
      function following ACLR demonstrated hop-landing biomechanics previously
      associated with early patellofemoral osteoarthritis. Therefore, interventions
      aimed at improving hop landing biomechanics in people with poor knee function are
      likely required. LEVEL OF EVIDENCE: III, Cross-sectional study.

PMID- 30293182
TI  - The reversed dynamic patellar apprehension test mimics anatomical complexity in
      lateral patellar instability.
AB  - PURPOSE: To develop a dynamic physical examination test that functionally
      simulates actual patellar instability events and that mimics the range of
      patellar stabilizer insufficiency in an individual patient. METHODS: Seventy
      eight consecutive patients (male/female 35/43; mean age 22 +/- 7 years) with
      recurrent lateral patellar instability and 35 controls (male/female 16/19; mean
      age 31 +/- 14 years) were prospectively evaluated using the reversed dynamic
      patellar apprehension test (ReDPAT). Anatomical predisposition was assessed
      according to Dejour's classification of trochlear dysplasia, tibial tuberosity
      trochlear groove distance, tibial tuberosity-posterior cruciate ligament
      distance, patellar height, and varus/valgus malalignment. RESULTS: The study
      group had an average of 3.4 +/- 1.0 (1-6) anatomical risk factors for lateral
      patellar dislocation. Severe trochlear dysplasia (84%) and patella alta (49%)
      were the most common. Test sensitivity and specificity was 93.7% (95% CI 0.8584
      0.9791) and 88.2% (95% CI 0.7255-0.9670), respectively. The positive predictive
      value reached 94.9% (95% CI 0.8739-0.9859) and the negative predictive value was
      85.7% (95% CI 0.6974-0.9519). The ReDPAT results became positive at a mean knee
      flexion angle of 58 degrees  +/- 17 degrees  (20 degrees -90 degrees ). Knee
      flexion angle correlated significantly with the severity of trochlear dysplasia
      (p = 0.018), valgus deformity (p = 0.011), and the total number of anatomical
      risk factors (p = 0.02). CONCLUSION: This study introduced the reversed dynamic
      patellar apprehension test as a reliable clinical examination tool in the
      assessment of lateral patellar instability. The results of this study indicate
      that the degree of knee joint flexion at which the provocative sense of
      apprehension becomes positive correlates with severity of trochlear dysplasia,
      valgus deformity and the total number of anatomical risk factors for patellar
      instability. This test indicates the patient-specific end of stable patellar
      tracking and the beginning of patellar stabilizer insufficiency. Therefore, this
      test might be helpful in deciding for or against a bony procedure in the
      treatment of patellar dislocation. LEVEL OF EVIDENCE: II.

PMID- 30293183
TI  - Social connectivity among female Tibetan macaques (Macaca thibetana) increases
      the speed of collective movements.
AB  - Social network analysis provides insights into patterns of group movements in
      primates, but fewer studies to date have focused on the dynamics of how such
      movements occur. In this study, we proposed and tested two hypotheses about the
      influence of sex on social connectivity and group movement in Tibetan macaques
      (Macaca thibetana): (1) adult females are socially more connected than are adult
      males and (2) social connectivity facilitates the speed of collective decision
      making. We collected data from 128 successful collective movements (>= 2
      individuals followed an initiator within 5 min) over a 2-month period in a group
      of adult Tibetan macaques at Mt. Huangshan, China. Although high-ranking
      individuals of both sexes in our dataset were more central in their social
      network than were low-ranking individuals, our results show that affiliations
      between females were stronger, with more preferred associations than those
      between males. Groups with more females reached collective decisions faster than
      groups with fewer females. We conclude that female Tibetan macaques use their
      social networks to enhance the speed of collective decision-making, which may
      have associated fitness benefits.

PMID- 30293184
TI  - Clinical evaluation of a low-shrinkage resin composite in endodontically treated
      premolars: 3-year follow-up.
AB  - OBJECTIVES: This study compared the 3-year clinical performance of a low
      shrinkage silorane-based composite material with that of a methacrylate-based
      composite material in the restoration of endodontically treated premolar teeth.
      MATERIALS AND METHODS: A total of 70 patients requiring a Class II composite
      resin restoration of a premolar tooth following root-canal treatment participated
      in the study. Cavities were restored with either a silorane-based restorative
      (Filtek Silorane + Silorane System Adhesive) or a methacrylate-based restorative
      (Filtek Z250 + Clearfil SE Bond) system applied according to the manufacturer's
      instructions. Restorations were evaluated by two blinded observers at five
      different time intervals (baseline; 6 months; 1, 2, and 3 years) according to
      modified USPHS criteria. Pearson's chi-square tests were used to examine
      differences in the clinical performance of the materials (retention, color match,
      marginal discoloration, secondary caries, anatomical form, marginal adaptation,
      and surface roughness), and Friedman and Wilcoxon tests were used to compare
      changes between baseline and each recall time, with a level of 0.05 considered
      statistically significant. RESULTS: After 3 years, no statistically significant
      differences in clinical performance were observed between the two materials (p >
      0.05). Intra-system comparisons revealed a statistically significant
      deterioration in color match, marginal discoloration, anatomical form, marginal
      adaptation, and surface roughness scores after 3 years for both systems. Although
      the difference was not significant at 3 years of follow-up, the level of
      deterioration in marginal adaptation and surface roughness was greater for the
      Filtek Silorane restoration than for the Filtek Z250 restoration at the 1 year
      follow-up (p > 0.05). CONCLUSION: Restorations of both materials were clinically
      acceptable after 3 years. The Filtek Silorane system did not appear to offer any
      clinical advantages over the methacrylate-based system when used in the
      restoration of Class II cavities in endodontically treated premolars. CLINICAL
      RELEVANCE: The restoration of endodontically treated premolars with minor or
      moderate loss of tooth structure can be directly performed either with silorane
      or methacrylate-based composite resins.

PMID- 30293185
TI  - Retentive force of PEEK secondary crowns on zirconia primary crowns over time.
AB  - OBJECTIVES: The purpose of the present study was to evaluate the retentive forces
      of CAD/CAM-fabricated polyetheretherketone (PEEK) secondary crowns on zirconia
      primary crowns over an artificial aging period representing 10 years of clinical
      service and compare them to electroformed secondary crowns made from pure gold.
      MATERIAL AND METHODS: Implant-supported zirconia primary crowns (N = 20) were
      CAD/CAM milled and provided either with electroformed secondary crowns (group ZE;
      N = 10) or CAD/CAM-fabricated PEEK secondary crowns (group ZP; N = 10). All
      secondary crowns were attached to a casted tertiary structure to ensure adequate
      stability. A universal testing machine was used to determine the retentive force
      values at baseline and after 1, 3, 5, and 10 years of simulated aging in the
      presence of artificial saliva. Data were analyzed applying Kolmogorov-Smirnov,
      Kruskal-Wallis, and Mann-Whitney U test. Level of significance was set at p <
      0.05. RESULTS: Retentive forces were not different for the groups ZE and ZP at
      baseline (median ZE 2.85 N; ZP 2.8 N; p <= 0.218). Because retentive force values
      changed significantly over simulation time for group ZE (Kruskal-Wallis; p <=
      0.028), the values between the test groups ZE and ZP differed significantly (Mann
      Whitney U) at 5 years (ZE 3.03 N; ZP 2.76 N; p <= 0.003) and 10 years (ZE 3.1 N;
      ZP 2.78 N; p <= 0.011). CONCLUSIONS: PEEK secondary crowns exhibit stable
      retentive force values over 10 years of simulated aging showing no signs of
      deterioration while the retentive force values of electroformed secondary crowns
      increase over time. CLINICAL RELEVANCE: PEEK might be a suitable alternative to
      proven metallic materials for the fabrication of secondary crowns.

PMID- 30293187
TI  - Micron-scale crack propagation in laser-irradiated enamel and dentine studied
      with nano-CT.
AB  - OBJECTIVES: The aim of this study was to see the effect of Er:YAG laser
      irradiation in dentine and compare this with its effect in enamel. The mechanism
      of crack propagation in dentine was emphasised and its clinical implications were
      discussed. MATERIALS AND METHODS: Coronal sections of sound enamel and dentine
      were machined to 50-MUm thickness using a FEI-Helios Plasma (FIB). The specimen
      was irradiated for 30 s with 2.94-MUm Er:YAG laser radiation in a moist
      environment, using a sapphire dental probe tip, with the tip positioned 2 mm away
      from the sample surface. One of the sections was analysed as a control and not
      irradiated. Samples were analysed using the Zeiss Xradia 810 Ultra, which allows
      high spatial resolution, nanoscale 3D imaging using X-ray computed tomography
      (CT). RESULTS: Dentine: In the peritubular dentine, micro-cracks ran parallel to
      the tubules whereas in the inter-tubular region, the cracks ran orthogonal to the
      dentinal tubules. These cracks extended to a mean depth of approximately 10 MUm
      below the surface. On the dentine surface, there was preferential ablation of the
      less mineralised intertubular dentine, and this resulted in an irregular
      topography associated with tubules. Enamel: The irradiated enamel surface showed
      a characteristic 'rough' morphology suggesting some preferential ablation along
      certain microstructure directions. There appears to be very little subsurface
      damage, with the prismatic structure remaining intact. CONCLUSIONS: A possible
      mechanism is that laser radiation is transmitted down the dentinal tubules
      causing micro-cracks to form in the dentinal tubule walls that tend to be limited
      to this region. CLINICAL RELEVANCE: Crack might be a source of fracture as it
      represents a weak point and subsequently might lead to a failure in restorative
      dentistry.

PMID- 30293188
TI  - Impact of endodontic post material on longitudinal changes in interproximal bone
      level: a randomized controlled pilot trial.
AB  - OBJECTIVES: Aim was to evaluate the impact of glass fiber versus titanium
      endodontic posts on the interproximal bone level around severely damaged
      endodontically treated teeth. MATERIALS AND METHODS: Thirty-eight participants of
      a randomized controlled trial on glass fiber (n = 18) and titanium post
      endodontic restorations (n = 20) received radiographs at two different times
      after post placement (T0 = <12 months and T1 = 36-72 months after post
      placement). A total of 76 radiographs were analyzed with an image-editing
      software. Medians of changes in mesial and distal interproximal bone level (?MBL,
      ?DBL) were calculated and tested for statistical significance with respect to
      post material using Mann-Whitney U test (p < 0.05). Impact of post material on
      bone level changes was assessed in multilevel mixed-effect linear regression
      models. RESULTS: The mean observation period was 54 months for glass fiber and 50
      months for titanium posts. Interproximal bone loss was small in both groups
      during the study period with no significant differences between groups (glass
      fiber group, ?MBL = - 0.03 mm and ?DBL = - 0.06 mm; titanium group, ?MBL = - 0.07
      mm and ?DBL = - 0.17 mm; both p > 0.05). Overall, impact of post material on bone
      loss was almost negligible with a nonsignificant difference between materials of
      0.10 mm during the entire study period. CONCLUSION: The rigidity of endodontic
      post material has no impact on the level of alveolar bone support of severely
      damaged endodontically treated teeth. CLINICAL RELEVANCE: Post-endodontic
      restorations of severely damaged teeth can achieve steady levels of periodontal
      bone support as a parameter of periodontal health, irrespective of post material.

PMID- 30293186
TI  - Effect of EDTA root conditioning on the outcome of coronally advanced flap with
      connective tissue graft: a systematic review and meta-analysis.
AB  - OBJECTIVES: CAF in combination with a connective tissue graft (CTG) is considered
      the technique of choice for treating gingival recessions (GRs). Among the many
      recognized factors that can affect the outcomes, the use of chemical agents has
      been proposed. The effect of EDTA, as a commonly used agent, remains
      controversial. Therefore, the aim of this review was to assess the efficacy of
      EDTA root conditioning when combined to CAF + CTG. MATERIAL AND METHODS: A
      literature search was conducted to identify randomized clinical trials (RCTs)
      that performed CAF + CTG with and without EDTA for root coverage procedures. The
      following outcomes were assessed: recession reduction (Rec Red), complete root
      coverage (CRC), keratinized tissue gain (KT gain), clinical attachment level
      changes (CAL gain), and changes in pocket depth (PD changes). RESULTS: Fourteen
      RCTs (575 GRs) were included and analyzed. Six articles were included in the EDTA
      group, with 8 in the non-EDTA group. Meta-analyses revealed statistically
      significant differences for the outcomes of Rec Red (3.68 mm versus 3.07 mm), CAL
      gain (4.15 mm versus 3.07 mm), and PD changes (- 0.44 mm versus 0.27 mm) in favor
      of the EDTA group, while outcomes of CRC (odds ratio of 1.15) and KT gain (1.98
      mm versus 1.62 mm) were not significantly different. CONCLUSIONS: Limited
      evidence is available when evaluating the effectiveness of EDTA root conditioning
      with CAF + CTG. However, the adjunct application of EDTA with CAF + CTG appears
      to be beneficial. CLINICAL RELEVANCE: The adjunct application of EDTA may provide
      benefits when performing root coverage procedure via CAF + CTG.

PMID- 30293189
TI  - Screening of HNF1A and HNF4A mutation and clinical phenotype analysis in a large
      cohort of Chinese patients with maturity-onset diabetes of the young.
AB  - AIMS: The study aimed to screen the HNF1A and HNF4A mutation in a large Chinese
      cohort of high clinical suspicion of maturity-onset diabetes of the young (MODY)
      patients and characterize the clinical features of those patients. The
      performance of hsCRP as a biomarker to differentiate MODY3 from early onset T2DM
      was also evaluated. METHODS: A total of 74 patients with a strong clinical
      suspicion of MODY from 59 families and 33 newly diagnosed early-onset T2DM were
      included. HNF1A and HNF4A mutations were analyzed by Sanger sequencing. ROC
      curves were used to identify the optimal cutoff of hsCRP. RESULTS: One novel
      (c.864_865insG) and six recurrent HNF1A mutations (R203H, R263H, P379T, L422P,
      P519L and c.873delC) in 17 patients from 8 families (13.6%), as well as one novel
      HNF4A (R331H) mutation were identified. Nonspecific clinical presentations were
      observed in MODYX compared to MODY3 patients. MODY3 subjects exhibited with
      younger, lower BMI, TG, fasting and postprandial C-peptide, higher HDL than T2DM.
      Particularly, we confirmed serum hsCRP was lower in MODY3 than T2DM. ROC curve
      showed a good discrimination with an AUC of 0.852 and identified a cutoff hsCRP
      of 0.79 (75% sensitivity and 83% specificity). Good glycemic control was observed
      in all identified patients after switching to glimepiride therapy. CONCLUSIONS:
      The prevalence of HNF1A mutation was relatively lower in Mainland China and HNF4A
      mutation was rare. Serum hsCRP concentrations performed well in discriminating
      MODY3 from T2DM. Molecular diagnosis of MODY3/1 did transform management in
      clinical practice and facilitated the glycemic control.

PMID- 30293190
TI  - Periampullary Diverticula and ERCP Outcomes: A Systematic Review and Meta
      Analysis.
AB  - INTRODUCTION: Periampullary diverticulum (PAD) is most often asymptomatically
      found in elderly population. ERCP in the presence of PAD is technically
      challenging since the location and orientation of the ampulla could be altered.
      Various studies have reported differing results on the technical success and
      safety outcomes of ERCP in the presence of PAD. We aimed at a meta-analysis of
      such studies to assess the technical success and the occurrence of complications
      during ERCP in patients with PAD. METHODS: We conducted a comprehensive search of
      several databases and conference proceedings including PubMed, EMBASE, and Web of
      Science databases (earliest inception to October 2017). The search was done in
      accordance with PRISMA guidelines to identify studies. Studies that reported on
      the ERCP outcomes based on the presence of PAD were included. Both prospective
      and retrospective studies, manuscripts and abstracts were included. Only articles
      in English literature were included. The primary analysis focused on the overall
      technical success of ERCP in the presence of PAD, and the secondary analysis was
      to estimate the risk of occurrence of complications. RESULTS: Our search resulted
      in 16 studies that were included for final analysis. These 16 studies reported on
      2794 patients, who had PAD, and the control group included 13,032 patients, who
      did not have a PAD during ERCP. Our meta-analysis of this data showed an Odd's
      ratio estimate of having a successful ERCP procedure in patients with PAD to be
      0.51 [95% C.I. (0.35-0.72)] when compared to patients without it. This was
      statistically significant, with a p value 0.00. Considerable heterogeneity was
      noted among the studies. The heterogeneity proportion was quantified at 74.6%
      based on I2 statistic. The secondary outcomes measured were complications. We
      analyzed the pooled Post-ERCP Pancreatitis (PEP), cholangitis, perforation, and
      bleeding. Only those studies that had the data for these complications in both
      the study and the control groups were selected. PEP: The pooled Odd's estimate of
      having PEP was 1.28, [95% C.I (0.88-1.87)] from 12 studies reporting on 1863
      patients with PAD in comparison with 7803 patients without it. The risk of PEP
      occurrence tended to be more in the group without PAD, though it was not
      statistically significant, with a p value 0.20. There was some heterogeneity
      observed between the studies, with the quantification I2 statistic being 28.6%.
      Our analysis shows that having PAD does not put a patient at increased risk for
      PEP. Bleeding: The pooled Odds estimate was 1.69, 95% C.I. 0.88-3.25 from nine
      studies reporting on 1816 patients with PAD in comparison with 5327 patients
      without it. This was not statistically significant, p value 0.11. Considerable
      heterogeneity was noted, with I2 being 55.7%. The risk of having a bleed was
      noted to be more in control group, and having PAD did not put patients at
      increased risk for bleeding during an ERCP procedure. Perforation: Patients with
      PAD undergoing ERCP were not at increased risk for perforation. Seven studies
      reported on this complication. This was noted in seven patients out of 1245 in
      study group, and 19 patients out of 4912 in control group. The pooled Odd's
      estimate was 1.24, 95% C.I. 0.54-2.87. There was no statistical significance, p
      value 0.61. No heterogeneity was noted among the studies included in this
      analysis. Cholangitis: Only four studies reported on this complication. In a
      total of 778 patients in study group, four had cholangitis and eight had this
      complication out of 3886 patients in the control group. The pooled Odd's was
      2.12, 95% C.I. 0.61-7.33. There was no statistical significance, p value 0.24. No
      heterogeneity was noted. CONCLUSION: ERCP is technically feasible and
      increasingly successful when performed by experts in the presence of PAD. The
      risk of complications such as PEP, bleeding, perforation and cholangitis does not
      differ between ERCP done in patients with and without PAD.

PMID- 30293192
TI  - Biological studies of synthesized silver nanoparticles using Prosopis farcta.
AB  - The evaluation of cytotoxic and apoptotic activities of silver nanoparticles (Ag
      NPs) synthesized by aqueous extract of Prosopis farcta was investigated against
      lung (A549) and colon (HT-29) cell lines. The cytotoxic activity of nanoparticles
      was performed using MTT assay, while their apoptotic activity was tested using
      TUNEL method. The obtained results of MTT showed that the cell viability of A549
      was dependent on the nanoparticles concentration and incubation time. Therefore,
      although the cytotoxic effect increased as the Ag-NPs concentration and
      incubation time heightened, yet the viability of HT-29 cells seems to be
      dependent only on the incubation time. The apoptotic results of the nanoparticles
      showed more than 50% of apoptosis on A549 and HT-29 cell lines, which in this
      case, HT-29 demonstrated 100% apoptosis at concentrations of more than 400 ug/ml.
      It seems that Ag-NPs synthesized using P. farcta extract can serve as anti-cancer
      agent in the treatment many cancers through creating or discovering new drug
      forms.

PMID- 30293191
TI  - Pancreas Pathology During the Natural History of Type 1 Diabetes.
AB  - PURPOSE OF REVIEW: We provide an overview of pancreas pathology in type 1
      diabetes (T1D) in the context of its clinical stages. RECENT FINDINGS: Recent
      studies of pancreata from organ donors with T1D and non-diabetic donors
      expressing T1D-associated autoantibodies reveal pathological changes/disease
      mechanisms beyond the well-known loss of beta cells and lymphocytic infiltrates
      of the islets (insulitis), including beta-cell stress, dysfunction, and viral
      infections. Pancreas pathology evolves through disease stages, is asynchronous,
      and demonstrates a chronic disease that remains active years after diagnosis.
      Critically, beta-cell loss is not complete at onset, although young age is
      associated with increased severity. The recognition of multiple pathogenic
      alterations and the chronic nature of disease mechanisms during and after the
      development of T1D inform improved clinical trial design and reveal additional
      targets for therapeutic manipulation, in the context of an expanded time window
      for intervention.

PMID- 30293193
TI  - Successful radiofrequency catheter ablation of atrial fibrillation is associated
      with improvement in left ventricular energy loss and mechanics abnormalities.
AB  - Dissipative energy loss (EL), an index of inefficient blood flow, has not been
      studied in patients with atrial fibrillation (AF). We therefore assessed the
      effect of AF and of successful catheter ablation on left ventricular (LV) EL and
      global longitudinal strain (GLS) to explore the effect of inefficient blood flow
      on LV remodeling. In 53 patients undergoing catheter ablation for AF (AF group),
      LV EL (in mW/m) was evaluated by vector flow mapping (VFM) during systole
      (ELsys), early diastole (ELed) and atrial contraction phase (ELac), and GLS was
      calculated by two-dimensional tissue tracking (2DTT). Of the 53 patients, 37
      patients who sustained sinus rhythm and completed echocardiographic evaluation at
      baseline and at 3 and 6 months follow-up were examined for change in EL and GLS.
      The latter parameters also were assessed in 44 age- and sex-matched controls. At
      baseline in AF group, ELsys and ELed were significantly higher (3.97 +/- 2.29 vs.
      3.14 +/- 1.01; and 9.22 +/- 5.01 vs. 3.89 +/- 1.51; both P < 0.05, respectively),
      and GLS was lower (- 16.66 +/- 3.50 vs. - 19.95 +/- 2.40, P < 0.05) than in
      controls. During follow-up after catheter ablation, ELsys and ELed significantly
      improved at 3 months, and almost normalized at 6 months (both P < 0.05); GLS also
      improved significantly (P < 0.05). In multivariate logistic regression analysis,
      ELed was the only independent predictor for maintenance of sinus rhythm at 1-year
      follow-up (hazard ratio, 1.254; 95% confidence interval 1.073-1.467). VFM and
      2DTT revealed impaired LV EL and GLS in patients with AF. Successful catheter
      ablation appeared to ameliorate impairment in intraventricular flow and
      mechanics.

PMID- 30293195
TI  - Bioprocesses for 2-phenylethanol and 2-phenylethyl acetate production: current
      state and perspectives.
AB  - 2-Phenylethanol (2-PE) and 2-phenethyl acetate (2-PEA) are valuable generally
      recognized as safe flavoring agents widely used in industry. Perfumes,
      pharmaceuticals, polishes, and personal care products, are some of the final
      products using these compounds as additives due to their rose-like odor. Also, 2
      PE is used in disinfectants, pest control, and cleaning products due to its
      biocide capability. Although most of these additives production are derived from
      chemical synthesis, the current trend of consumers to prefer natural products has
      contributed to the development of biotechnological approaches as an alternative
      way to obtain natural 2-PE and 2-PEA. The most efficient route to bioproduce
      these compounds is through the bioconversion of L-phenylalanine via the Ehrlich
      pathway, and most of the advances have been focused on the development of this
      process. This review compiles the most recent developments in the
      biotechnological production of 2-PE and 2-PEA, indicating the most studied
      strains producing 2-PE and 2-PEA, the current advances in the in situ product
      recovery in liquid systems, an overview of the strain developments, and the
      progress in the use of residue-based systems. Future research should address the
      need for more sustainable and economic systems such as those using wastes as raw
      materials, as well as the scale-up of the proposed technologies.

PMID- 30293196
TI  - Biotransformation of industrial tannins by filamentous fungi.
AB  - Tannins are secondary metabolites that are widely distributed in the plant
      kingdom. They act as growth inhibitors for many microorganisms: they are released
      upon microbial attack, helping to fight infection in plant tissues. Extraction of
      tannins from plants is an active industrial sector with several applications,
      including oenology, animal feeding, mining, the chemical industry, and, in
      particular, the tanning industry. However, tannins are also considered very
      recalcitrant pollutants in wastewater of diverse origin. The ability to grow on
      plant substrates rich in tannins and on industrial tannin preparations is usually
      considered typical of some species of fungi. These organisms are able to tolerate
      the toxicity of tannins thanks to the production of enzymes that transform or
      degrade these substrates, mainly through hydrolysis and oxidation. Filamentous
      fungi capable of degrading tannins could have a strong environmental impact as
      bioremediation agents, in particular in the treatment of tanning wastewaters.

PMID- 30293197
TI  - PET imaging of noradrenaline transporters in Parkinson's disease: focus on scan
      time.
AB  - OBJECTIVE: In subjects with idiopathic Parkinson's disease (PD) the functional
      state of the locus coeruleus and the subtle derangements in the finely tuned
      dopamine-noradrenaline interplay are largely unknown. The PET ligand (S,S)-[11C]
      O-methylreboxetine (C-11 MRB) has been described to reliably bind noradrenaline
      transporters but long scanning protocols might hamper its use, especially in
      patients with PD. We aimed to assess the feasibility of reducing C-11 MRB scans
      to 30 min. METHODS: Ten patients with idiopathic PD underwent dynamic C-11 MRB
      PET (120 min duration) and brain magnetic resonance imaging. Model-based (i.e.,
      simplified and multilinear reference tissue model 2) non-displaceable binding
      potentials (BP) of selected brain regions were analyzed for a 90 min scan
      protocol and compared with BP derived from static 30-min data with different
      starting times (30, 40, 50 and 60 min) after C-11 MRB injection. Intraclass
      correlation coefficient and linear regression analysis were used to explore the
      association between BP of different scan durations. Spearman's rho served to
      describe the correlation of BP with demographic and clinical parameters. RESULTS:
      With respect to kinetic models, BP50-80 and BP60-90 showed the best correlation
      in several brain areas (R2 range 0.95-98; p < 0.001). The thalamus showed the
      highest BP on average. No correlation between BP, clinical and demographic
      characteristics was observed. CONCLUSIONS: An acquisition time of 30 min,
      starting 50 or 60 min after C-11 MRB injection, allows a reliable estimation of
      noradrenaline transporter binding values in Parkinsonian people. A short
      acquisition time can significantly reduce the discomfort of Parkinsonian patients
      and facilitate PET studies, especially in the medication-off-state.

PMID- 30293198
TI  - Bone Microstructure in Response to Vitamin D3 Supplementation: A Randomized
      Placebo-Controlled Trial.
AB  - Vitamin D supplementation is often used in the prevention and treatment of
      osteoporosis, but the role of vitamin D has lately been questioned. We aimed to
      investigate the effect of 3 months of daily vitamin D3 supplementation (70 ug
      [2800 IU] vs. placebo) initiated in winter months on bone health. This study is a
      double-blinded placebo-controlled randomized trial. Bone health was assessed by
      bone turnover markers, DXA, HRpQCT, and QCT scans. The participants were 81
      healthy postmenopausal women with low 25(OH)D (< 50 nmol/l) and high PTH levels
      (> 6.9 pmol/l) at screening. Vitamin D3 supplementation significantly increased
      levels of 25(OH)D and 1,25(OH)2D by 59 nmol/l and 19 pmol/l, respectively,
      whereas PTH was reduced by 0.7 pmol/l (all p < 0.0001). Compared with placebo,
      vitamin D3 did not affect bone turnover markers, aBMD by DXA or trabecular bone
      score. Vitamin D3 increased trabecular vBMD (QCT scans) in the trochanter region
      (0.4 vs. - 0.7 g/cm3) and the femoral neck (2.1 vs. - 1.8 g/cm3) pall < 0.05.
      HRpQCT scans of the distal tibia showed reduced trabecular number (- 0.03 vs.
      0.05 mm-1) and increased trabecular thickness (0.001 vs. - 0.005 mm), as well as
      an improved estimated bone strength as assessed by failure load (0.1 vs. - 0.1
      kN), and stiffness (2.3 vs. - 3.1 kN/mm pall <= 0.01). Changes in 25(OH)D
      correlated significantly with changes in trabecular thickness, stiffness, and
      failure load. Three months of vitamin D3 supplementation improved bone strength
      and trabecular thickness in tibia, vBMD in the trochanter and femoral neck, but
      did not affect aBMD.

PMID- 30293199
TI  - Posttraumatic stress disorder and development of premenstrual syndrome in a
      longitudinal cohort of women.
AB  - We examined the association between posttraumatic stress disorder (+PTSD)
      symptoms and incident premenstrual syndrome (PMS) in a longitudinal study with 14
      years follow-up of 2924 women aged 27-44. Compared to women with no trauma
      exposure, women with trauma/PTSD were at significantly increased risk of PMS (p
      trend < .001): 1) trauma/no PTSD odds ratio (OR) = 1.31 [95% confidence interval
      (CI) 1.05-1.63], 2) 1-3 PTSD symptoms OR = 1.71 [95% CI = 1.33-2.20], 3) 4-5 PTSD
      symptoms OR = 2.90 [95% CI = 2.07-4.05], and 4) 6-7 PTSD symptoms OR = 3.42 [95%
      CI = 2.18-5.36].

PMID- 30293200
TI  - Irritant Contact Dermatitis.
AB  - Contact dermatitis accounts for 95% of occupational skin disorders. Irritant
      contact dermatitis (ICD) is often caused by cumulative exposure to weak
      irritants, accounting for 80% of all cases of contact dermatitis. ICD can co
      exist with atopic dermatitis (AD) and allergic contact dermatitis (ACD). Patients
      with AD and ACD may have a lower inflammatory threshold for developing ICD.
      Therefore, it needs to be distinguished from lesions of AD and ACD. ICD Patients
      report stinging and burning in excess of pruritus. Pruritus is classically
      reported by patients with AD and ACD. ICD lesions are typically well-demarcated
      unlike AD and ACD. ICD is diagnosed by exclusion. Patients undergo testing to
      rule out type I and type IV hypersensitivity. Negative results suggest a
      diagnosis of ICD. Management consists of irritant identification and avoidance
      with regular emollient use. Although ICD is more common in certain occupations,
      genetics and environment play significant roles in its development.

PMID- 30293201
TI  - Characterization of Maf1 in Arabidopsis: function under stress conditions and
      regulation by the TOR signaling pathway.
AB  - MAIN CONCLUSION: Maf1 repressor activity is critical for plant survival during
      environmental stresses, and is regulated by its phosphorylation/dephosphorylation
      through the activity of TOR and PP4/PP2A phosphatases. Maf1 is a global repressor
      of RNA polymerase III (Pol III), and is conserved in eukaryotes. Pol III
      synthesizes small RNAs, 5S rRNA, and tRNAs that are essential for protein
      translation and cell growth. Maf1 is a phosphoprotein and dephosphorylation of
      Maf1 promotes its repressor activity in yeast and mammals. Plant Maf1 was
      identified in citrus plants as a canker elicitor-binding protein, and citrus Maf1
      represses cell growth associated with canker development. However, functions of
      plant Maf1 under diverse stress conditions and its regulation by the target of
      rapamycin (TOR) signaling components are poorly understood. In this study, the
      Arabidopsis maf1 mutants were more susceptible to diverse stresses and treatment
      with the TOR inhibitor Torin-1 than wild-type plants. The maf1 mutants expressed
      higher levels of Maf1 target RNAs, including 5S rRNA and pre-tRNAs in leaf cells,
      supporting Pol III repressor activity of Arabidopsis Maf1. Cellular stresses and
      Torin-1 treatment induced dephosphorylation of Maf1, suggesting Maf1 activation
      under diverse stress conditions. TOR silencing also stimulated Maf1
      dephosphorylation, while silencing of catalytic subunit genes of PP4 and PP2A
      repressed it. Thus, TOR kinase and PP4/PP2A phosphatases appeared to oppositely
      modulate the Maf1 phosphorylation status. TOR silencing decreased the abundance
      of the target RNAs, while silencing of the PP4 and PP2A subunit genes increased
      it, supporting the positive correlation between Maf1 dephosphorylation and its
      repressor activity. Taken together, these results suggest that repressor activity
      of Maf1, regulated by the TOR signaling pathway, is critical for plant cell
      survival during environmental stresses.

PMID- 30293202
TI  - Evolutionary and functional analyses of the 2-oxoglutarate-dependent dioxygenase
      genes involved in the flavonoid biosynthesis pathway in tobacco.
AB  - MAIN CONCLUSION: This study illustrates the differences in the gene structure of
      2-oxoglutarate-dependent oxygenase involved in flavonoid biosynthesis (2ODD-IFB),
      and their potential roles in regulating tobacco flavonoid biosynthesis and plant
      growth. Flavonol synthase (FLS), anthocyanidin synthase (ANS), and flavanone
      3beta-hydroxylase belong to the 2-oxoglutarate-dependent (2ODD) oxygenase family,
      and each performs crucial functions in the biosynthesis of flavonoids. We
      identified two NtFLS genes, two NtANS genes, and four NtF3H genes from Nicotiana
      tabacum genome, as well as their homologous genes in the N. sylvestris and N.
      tomentosiformis genomes. Our phylogenetic analysis indicated that these three
      types of genes split from each other before the divergence of gymnosperms and
      angiosperms. FLS evolved faster in the eudicot plants, whereas ANS evolved faster
      in the monocot plants. Gene structure analysis revealed two fragment insertions
      occurred at different times in the intron one position of tobacco FLS genes.
      Homologous protein modeling revealed distinct structures in the N terminus of the
      tobacco 2ODD oxygenases. We found that the expression patterns of genes encoding
      tobacco 2ODD oxygenases in flavonoids biosynthesis (2ODD-IFB) did not determine
      the accumulation patterns of flavonoids among various tobacco tissues, but
      strongly affected the concentration of flavonoids in the tissues, where they were
      biosynthesized. More carbon resource flowed to the flavonol biosynthesis when
      NtANS gene was silenced, otherwise more anthocyanidin accumulated when NtFLS gene
      was repressed. This study illustrates the 2ODD-IFB gene structure evolution,
      differences among their protein structures, and provides a foundation for
      regulating plant development and altering flavonoid content and/or composition
      through the manipulation of plant 2ODD-IFB genes.

PMID- 30293204
TI  - Role of prolonged blood culture incubation in infective endocarditis diagnosis.

PMID- 30293203
TI  - The application of finite element modelling based on clinical pQCT for
      classification of fracture status.
AB  - Fracture risk assessment using dual-energy X-ray absorptiometry (DXA) frequently
      fails to diagnose osteoporosis amongst individuals who later experience fragility
      fractures. Hence, more reliable techniques that improve the prediction of
      fracture risk are needed. In this study, we evaluated a finite element (FE)
      modelling framework based on clinical peripheral quantitative computed tomography
      (pQCT) imaging of the tibial epiphysis and diaphysis to predict the stiffness at
      these locations in compression, shear, torsion and bending. The ability of these
      properties to identify a group of women who had recently sustained a low-trauma
      fracture from an age- and weight-matched control group was determined and
      compared to clinical pQCT and DXA properties and structural properties based on
      composite beam theory. The predicted stiffnesses derived from the FE models and
      composite beam theory were significantly different (p < 0.05) between the control
      and fracture groups, whereas no meaningful differences were observed using DXA
      and for the stress-strain indices (SSIs) derived using pQCT. The diagnostic
      performance of each property was assessed by the odds ratio (OR) and the area
      under the receiver operating curve (AUC), and both were greatest for the FE
      predicted shear stiffness (OR 16.09, 95% CI 2.52-102.56, p = 0.003) (AUC: 0.80,
      95% CI 0.67-0.93). The clinical pQCT variable total density (rhotot) and a number
      of structural and FE-predicted variables had a similar probability of correct
      classification between the control and fracture groups (i.e. ORs and AUCs with
      mean values greater than 5.00 and 0.80, respectively). In general, the diagnostic
      characteristics were lower for variables derived using DXA and for the SSIs (i.e.
      ORs and AUCs with mean values of 1.65-2.98 and 0.64-0.71, respectively). For all
      properties considered, the trabecular-dominant tibial epiphysis exhibited
      enhanced classification characteristics, as compared to the cortical-dominant
      tibial diaphysis. The results of this study demonstrate that bone properties may
      be derived using FE modelling that have the potential to enhance fracture risk
      assessment using conventional pQCT or DXA instruments in clinical settings.

PMID- 30293205
TI  - Multimodal imaging of multifocal chorioretinitis secondary to endogenous candida
      infection.
AB  - PURPOSE: To present multimodal imaging of multifocal chorioretinitis secondary to
      endogenous candida infection in a young adult. METHODS: A 49-year-old woman who
      presented for evaluation of bilateral endogenous candida chorioretinitis
      underwent complete ophthalmic examination, in addition to fundus photography
      (FP), enhanced depth imaging optical coherence tomography, fundus
      autofluorescence (FAF), fluorescein angiography (FA), indocyanine green
      angiography (ICGA) and optical coherence tomography angiography (OCTA). RESULTS:
      Multimodal imaging of both eyes of the patient affected by endogenous candida
      chorioretinitis was performed. FP showed multiple white chorioretinal lesions at
      the posterior pole, FAF showed dark dot at the posterior pole surrounded by
      hyperautofluorescence area, FA showed early hyperfluorescence round perifoveal
      lesion at the posterior pole and small hyperfluorescence dots under the inferior
      retinal vessels. Early ICGA showed hypofluorescence dots at the posterior pole.
      Late ICGA showed dark hypofluorescence dots at the posterior pole surrounded by
      faint hyperautofluorescent ring. OCTA showed dark areas corresponded to
      hypoperfusion areas seen with early ICGA. CONCLUSION: We reported multimodal
      imaging of an unusual occurrence of multifocal chorioretinitis due to
      immunosuppression. These findings suggested that the infection resulted from
      choroidal infiltration via the short posterior ciliary arteries with resultant
      breakthrough into the retina, rather than via the central retinal artery. By
      comparing findings on OCTA with data obtained from traditional systems, we are
      gaining essential information on the pathogenesis of endogenous candida
      chorioretinitis.

PMID- 30293194
TI  - Safety of the fungal workhorses of industrial biotechnology: update on the
      mycotoxin and secondary metabolite potential of Aspergillus niger, Aspergillus
      oryzae, and Trichoderma reesei.
AB  - This review presents an update on the current knowledge of the secondary
      metabolite potential of the major fungal species used in industrial
      biotechnology, i.e., Aspergillus niger, Aspergillus oryzae, and Trichoderma
      reesei. These species have a long history of safe use for enzyme production. Like
      most microorganisms that exist in a challenging environment in nature, these
      fungi can produce a large variety and number of secondary metabolites. Many of
      these compounds present several properties that make them attractive for
      different industrial and medical applications. A description of all known
      secondary metabolites produced by these species is presented here. Mycotoxins are
      a very limited group of secondary metabolites that can be produced by fungi and
      that pose health hazards in humans and other vertebrates when ingested in small
      amounts. Some mycotoxins are species-specific. Here, we present scientific basis
      for (1) the definition of mycotoxins including an update on their toxicity and
      (2) the clarity on misclassification of species and their mycotoxin potential
      reported in literature, e.g., A. oryzae has been wrongly reported as an aflatoxin
      producer, due to misclassification of Aspergillus flavus strains. It is therefore
      of paramount importance to accurately describe the mycotoxins that can
      potentially be produced by a fungal species that is to be used as a production
      organism and to ensure that production strains are not capable of producing
      mycotoxins during enzyme production. This review is intended as a reference paper
      for authorities, companies, and researchers dealing with secondary metabolite
      assessment, risk evaluation for food or feed enzyme production, or considerations
      on the use of these species as production hosts.

PMID- 30293206
TI  - Aggressiveness of Localized Prostate Cancer: the Key Value of Testosterone
      Deficiency Evaluated by Both Total and Bioavailable Testosterone: AndroCan Study
      Results.
AB  - Failure rates after first-line treatment of localized prostate cancer (PCa)
      treatment remain high. Improvements to patient selection and identification of at
      risk patients are central to reducing mortality. We aimed to determine if cancer
      aggressiveness correlates with androgen levels in patients undergoing radical
      prostatectomy for localized PCa. We performed a prospective, multicenter cohort
      study between June 2013 and June 2016, involving men with localized PCa scheduled
      to undergo radical prostatectomy. Clinical and hormonal patient data
      (testosterone deficiency, defined by total testosterone (TT) levels < 300 ng/dL
      and/or bioavailable testosterone (BT) levels < 80 ng/dL) were prospectively
      collected, along with pathological assessment of preoperative biopsy and
      subsequent radical prostatectomy specimens, using predominant Gleason pattern
      (prdGP) 3/4 grading. Of 1343 patients analyzed, 912 (68%) had prdGP3 PCa and 431
      (32%) had high-grade (prdGP4, i.e., ISUP >= 3) disease on prostatectomy
      specimens. Only moderate concordance in prdGP scores between prostate biopsies
      and prostatectomy specimens was found. Compared with patients with prdGP3 tumors
      (i.e., ISUP <= 2), significantly more patients with prdGP4 cancers had
      demonstrable hypogonadism, characterized either by BT levels (17.4% vs. 10.7%, p
      < 0.001) or TT levels (14.2% vs. 9.7%, p = 0.020). BT levels were also lower in
      patients with prdGP4 tumors compared to those with prdGP3 disease. Testosterone
      deficiency (defined by TT and/or BT levels) was independently associated with
      higher PCa aggressiveness. BT is a predictive factor for prdGP4 disease, and
      evaluating both TT and BT to define hypogonadism is valuable in preoperative
      assessment of PCa (AndroCan Trial: NCT02235142).

PMID- 30293207
TI  - Nivolumab for Treating Metastatic or Unresectable Urothelial Cancer: An Evidence
      Review Group Perspective of a NICE Single Technology Appraisal.
AB  - As part of its single technology appraisal (STA) process, the National Institute
      for Health and Care Excellence (NICE) invited the manufacturer (Bristol-Myers
      Squibb) of nivolumab (Opdivo(r)) to submit evidence of its clinical and cost
      effectiveness for metastatic or unresectable urothelial cancer. Kleijnen
      Systematic Reviews Ltd, in collaboration with Maastricht University Medical
      Centre+, was commissioned to act as the independent Evidence Review Group (ERG),
      which produced a detailed review of the evidence for the clinical and cost
      effectiveness of the technology, based on the company's submission to NICE.
      Nivolumab was compared with docetaxel, paclitaxel, best supportive care and
      retreatment with platinum-based chemotherapy (cisplatin plus gemcitabine, but
      only for patients whose disease has had an adequate response in first-line
      treatment). Two ongoing, phase I/II, single-arm studies for nivolumab were
      identified, but no studies directly compared nivolumab with any specified
      comparator. Evidence from directly examining the single arms of the trial data
      indicated little difference between the outcomes measured from the nivolumab and
      comparator studies. A simulated treatment comparison (STC) analysis was used in
      an attempt to reduce the bias induced by naive comparison, but there was no clear
      evidence that risk of bias was reduced. Multiple limitations in the STC were
      identified and remained. The effect of an analysis based on different
      combinations of covariates in the prediction model remains unknown. The ERG's
      concerns regarding the economic analysis included the use of a non-established
      response-based survival analysis method, which introduced additional uncertainty.
      The use of time-dependent hazard ratios produced overfitting and was not
      represented in the probabilistic sensitivity analysis. The use of a treatment
      stopping rule to cap treatment cost left treatment effectiveness unaltered. A
      relevant comparator was excluded from the base-case analysis. The revised ERG
      deterministic base-case incremental cost-effectiveness ratios based on the
      company's Appraisal Consultation Document response were L58,791, L78,869 and
      L62,352 per quality-adjusted life-year gained versus paclitaxel, docetaxel and
      best supportive care, respectively. Nivolumab was dominated by cisplatin plus
      gemcitabine in the ERG base case. Substantial uncertainties about the relative
      treatment effectiveness comparing nivolumab against all comparators remained.
      NICE did not recommend nivolumab, within its marketing authorisation, as an
      option for treating locally advanced, unresectable or metastatic urothelial
      carcinoma in adults who have had platinum-containing therapy, and considered that
      nivolumab was not suitable for use within the Cancer Drugs Fund.

PMID- 30293208
TI  - Effect of Synbiotic and Probiotic Supplementation on Serum Levels of Endothelial
      Cell Adhesion Molecules in Hemodialysis Patients: a Randomized Control Study.
AB  - : The aim of this study was to investigate the effect of synbiotic and probiotic
      supplementation on serum vascular dysfunction and necrosis markers in
      hemodialysis (HD) patients. In this randomized, double-blind, placebo-controlled
      trial, 75 HD patients were randomly assigned to either the synbiotic or probiotic
      or placebo group. The patients in the synbiotic group received 15 g of prebiotics
      and 5 g probiotic powder containing Lactobacillus acidophilus strain T16 (IBRC
      M10785), Bifidobacterium bifidum strain BIA-6, Bifidobacterium lactis strain BIA
      6, Bifidobacterium longum strain LAF-5 (2.7 * 107 CFU/g each) in sachets (n =
      25), whereas the probiotic group received 5 g probiotics same to the first group
      with 15 g of maltodextrin powder in sachets (n = 25) and the placebo group
      received 20 g of maltodextrin powder in sachets (n = 25) for 12 weeks. At
      baseline and the end of the study, serum concentrations of soluble intercellular
      adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type
      1 (sVCAM-1), cytokeratin 18 (CK-18) as the necrosis marker, uric acid, and
      phosphate levels were measured. Feces also were collected for microbiota colony
      counting. Serum ICAM-1 level reduced significantly in the synbiotic group after
      the intervention period (P = 0.02), and this reduction was significantly
      different in the synbiotic group in comparison to the placebo group (P = 0.03).
      Serum levels of VCAM-1 and CK-18 were not significantly different between the
      groups. However, the reduction in serum levels of VCAM-1 in the synbiotic group
      was significantly higher in comparison to the placebo group (P = 0.01).
      Multivariate linear regression analysis revealed that ? phosphate was the sole
      independent determinant of ?ICAM-1 (P = 0 < 001). The study indicated that
      synbiotic supplementation reduced serum ICAM-1 level, which is a risk factor for
      cardiovascular diseases in HD patients, but has no effect on the necrosis marker.
      TRIAL REGISTRATION: www.irct.ir (IRCT2017041233393N1).

PMID- 30293210
TI  - Minimally invasive treatment of postsurgical biliary complications: the role of
      interventional radiology.

PMID- 30293209
TI  - Update on Vaccinating the Patient With Inflammatory Bowel Disease.
AB  - PURPOSE OF REVIEW: Patients with inflammatory bowel disease (IBD) are at
      increased risk of infectious diseases independent of their immunosuppression
      status, and yet, studies suggest that this population is not receiving standard
      vaccinations at the same rate as the general population. This review seeks to
      understand why IBD patients may not be receiving recommended immunizations and to
      provide guidelines on vaccinating this vulnerable population. RECENT FINDINGS:
      Inactive vaccines are recommended for patients with IBD regardless of
      immunosuppression status due to the increased risk for many vaccine-preventable
      illnesses. Certain live vaccines can be administered to the immunocompromised
      patient with IBD. Additionally, many patients with IBD will be immunosuppressed
      some time in their disease course, further increasing their risk for infection.
      Despite this understanding, patients with IBD have poor vaccination rates.
      Inadequate knowledge, limited time with patients, and lack of consensus as to who
      is responsible for identifying and administering vaccinations are some of the
      most important barriers to vaccinating the patient with IBD. In this review, we
      discuss guidelines for vaccinating both the immunocompetent and immunosuppressed
      patient with IBD as well as provide vaccine-specific recommendations. The
      evidence suggests that patients with IBD are not receiving recommended
      vaccinations because of misconceptions on the part of patients as well as a
      paucity of knowledge by their health care team. Educational programs can be
      successfully implemented to increase knowledge about appropriate vaccinations and
      can ultimately increase vaccine uptake among patients with IBD. In the end,
      gastroenterologists and primary care physicians must work together with their
      patients with IBD to ensure that recommended vaccinations are administered.

PMID- 30293211
TI  - BRCA mutations: is everything said?
AB  - BACKGROUND: Mutations in the BRCA1 and BRCA2 genes constitute a risk factor for
      breast cancer development. BRCA mutation research has been an active field since
      the discovery of the genes, and new mutations in both genes are constantly
      described and classified according to several systems. AIM: We intend to provide
      an overview of the current state of BRCA1 and BRCA2 mutation description and
      classification. We wanted to know whether there was a trend towards a more
      frequently described mutation type and what the proportion of pathogenic
      mutations was. RESULTS: We found that, although new mutations are described each
      year as reflected in current database records, very few of them are reported in
      papers. Classification systems are highly heterogeneous and a consensus among
      them is still under development. Regarding their function, a large number of
      mutations are yet to be analyzed, a very complex task, due to the great number of
      possible variations and their diverse effect in the BRCA gene functions. After
      individual analysis, many variants of unknown significance turn out to be
      pathogenic, and many can disrupt interactions with other proteins involved in
      mechanisms such as DNA damage repair pathways. Recent data suggest that looking
      for mutation patterns or combinations would shed a wider light on BRCA-derived
      cancer susceptibility in the upcoming years.

PMID- 30293212
TI  - Racial/ethnic differences in the outcomes of patients with metastatic breast
      cancer: contributions of demographic, socioeconomic, tumor and metastatic
      characteristics.
AB  - PURPOSE: Population-based estimates of racial disparities in metastatic breast
      cancer are lacking. We quantified the contributions of demographic,
      socioeconomic, tumor, and metastatic characteristics to racial differences in
      metastatic breast cancer and characterized the most disproportional subgroup.
      METHODS: Patients diagnosed with metastatic breast cancer between 2010 and 2014
      were identified using the Surveillance, Epidemiology, and End Results database. A
      multivariable Cox proportional hazards model was used to adjust each set of
      variables. The excess relative risk of cancer-specific and all-cause death in non
      Hispanic black (NHB) versus non-Hispanic white women diagnosed with metastatic
      breast cancer was expressed as a percentage and was stratified by the age at
      diagnosis. RESULTS: We identified 13,066 female patients. NHB women exhibited
      substantially higher morbidity and mortality than women of other
      races/ethnicities. The greatest excess mortality risk for NHB women was observed
      in the young-onset group (18-49 years; hazard ratio: 1.57), followed by the
      middle-age group (50-64 years; hazard ratio: 1.42); the trend was not significant
      among the elderly group. Socioeconomic factors stably explained one-half of the
      excess risk, whereas the contribution of tumor characteristics obviously
      decreased with age (18-49 years, 40.7%; 50-64 years, 33.9%), and the metastatic
      pattern accounted for approximately one-tenth of the excess risk. Additionally,
      the disproportional death burden of NHB women persisted in less aggressive
      subgroups. CONCLUSIONS: By providing a comprehensive assessment of racial
      differences in the incidence and outcomes of patients with metastatic breast
      cancer, we urge the implementation of targeted preventive efforts in both the
      public health and clinical arenas.

PMID- 30293214
TI  - Ex vivo visualization of the trigeminal pathways in the human brainstem using
      11.7T diffusion MRI combined with microscopy polarized light imaging.
AB  - Classic anatomical atlases depict a contralateral hemispheral representation of
      each side of the face. Recently, however, a bilateral projection of each hemiface
      was hypothesized, based on animal studies that showed the coexistence of an
      additional trigeminothalamic tract sprouting from the trigeminal principal
      sensory nucleus that ascends ipsilaterally. This study aims to provide an
      anatomical substrate for the hypothesized bilateral projection. Three post-mortem
      human brainstems were scanned for anatomical and diffusion magnetic resonance
      imaging at 11.7T. The trigeminal tracts were delineated in each brainstem using
      track density imaging (TDI) and tractography. To evaluate the reconstructed
      tracts, the same brainstems were sectioned for polarized light imaging (PLI).
      Anatomical 11.7T MRI shows a dispersion of the trigeminal tract (tt) into a
      ventral and dorsal portion. This bifurcation was also seen on the TDI maps,
      tractography results and PLI images of all three specimens. Referring to a
      similar anatomic feature in primate brains, the dorsal and ventral tracts were
      named the dorsal and ventral trigeminothalamic tract (dtt and vtt), respectively.
      This study shows that both the dtt and vtt are present in humans, indicating that
      each hemiface has a bilateral projection, although the functional relevance of
      these tracts cannot be determined by the present anatomical study. If both tracts
      convey noxious stimuli, this could open up new insights into and treatments for
      orofacial pain in patients.

PMID- 30293215
TI  - The association between urinary sodium excretion and blood pressure in a
      community-based population: the Yamagata (Takahata) study.
AB  - BACKGROUND: The association between salt intake and blood pressure levels is
      still inconclusive, and may be influenced by patient characteristics. We thus
      conducted a community-based cross-sectional study. METHODS: This study included
      2297 subjects aged >= 40 years not on antihypertensive medication at the time of
      a health check-up. We examined the association between blood pressure levels and
      the estimated amount of 24-h urinary sodium excretion (e24hUNa) stratified by
      background characteristics. The 24-h urinary excretion levels of sodium and
      potassium were estimated from Kawasaki's equation using a spot urine sample.
      RESULTS: The association of systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) with e24hUNa was significantly positive in a multiple linear
      regression model adjusted for confounders including age, sex, smoking, alcohol
      consumption, body mass index, diabetes, hypercholesterolemia, renal function, and
      potassium excretion. The regression coefficients of changes in SBP and DBP per 1
      SD increase in e24hUNa (53 mEq/day) were + 1.91 mmHg and + 0.94 mmHg,
      respectively. In the subgroup analyses, the increase in SBP was especially
      greater in the elderly, in subjects with diabetes, and in subjects with reduced
      renal function compared to those in the counterparts. The association between SBP
      and e24hUNa was insignificant in subjects with eGFR >= 90 ml/min/1.73m2, while
      the association with progression of renal dysfunction was stronger and
      significant. CONCLUSIONS: These results demonstrated that the association between
      blood pressure and urinary sodium excretion was strengthened by characteristics
      of subjects such as aging, presence of diabetes, and renal impairment in the
      community-based population.

PMID- 30293216
TI  - Clinical significance of mesangial IgM deposition in patients with IgA
      nephropathy.
AB  - BACKGROUND: Glomerular immunoglobulin G deposition in patients with
      immunoglobulin A nephropathy (IgAN) has been shown to be associated with adverse
      renal outcomes. Clinical significance of mesangial immunoglobulin M (IgM)
      deposition in these patients remains to be proven. METHODS: One hundred patients
      who had a diagnosis of IgAN between 2001 and 2017 were enrolled. Patients were
      divided into two groups based on mesangial IgM deposition status. Groups were
      compared for demographic, clinical, and pathologic variables at baseline and in
      follow-up. Cox regression analysis was performed to evaluate the effect of
      mesangial IgM positivity on renal survival. RESULTS: IgM-positive group included
      51% of participants. Baseline demographic and clinical parameters were not
      significantly different between groups. Mesangial IgM deposition was
      significantly associated with a higher segmental sclerosis score (p = 0.008). At
      last visit, median serum creatinine was higher (p = 0.021) and eGFR was lower (p
      = 0.006) in IgM-positive group. Nineteen (19%) of all patients reached the
      combined primary outcome which includes doubling in serum creatinine or evolution
      to ESRD. Cumulative renal survival was lower (p = 0.001) and resistant disease
      was more frequent in IgM-positive group (p = 0.026). Renal survival at 15 years
      was 94.2% and 59.7% in IgM-negative and IgM-positive groups, respectively (p =
      0.006). Time-averaged proteinuria (HR 2.9; 95% CI 1.9-4.5; p < 0.001) and
      mesangial IgM deposition (HR, 13.2; 95% CI 1.9-93.1; p = 0.01) were found to be
      independent predictors of unfavorable renal outcomes. CONCLUSIONS: In conclusion,
      we demonstrated that mesangial IgM deposition independently associated with worse
      renal outcomes in patients with IgA nephropathy.

PMID- 30293217
TI  - Massive bone marrow necrosis revealing an HIV-related primary bone marrow
      lymphoma: a diagnostic challenge.
AB  - Bone marrow necrosis (BMN) is a condition that can be difficult to diagnose,
      requiring a hematologist experienced in bone marrow morphology. This diagnostic
      challenge should alert the clinician of a severe disease or a possible underlying
      malignancy, either hematological or a solid tumor. We describe the concomitant
      presence of a primary bone marrow lymphoma (diffuse large B-cell lymphoma-DLBCL),
      along with an extensive BMN in an HIV patient for the first time in a living
      individual. HIV infection, BMN and DLBCL presented a multifactorial crossword of
      molecular events underlying the complex pathophysiology. The exact precipitating
      pathophysiological events resulting in BMN remain obscure and provide their clear
      impact for future research. The present report is instructive and also contains a
      critical review of the literature related to the case presented.

PMID- 30293213
TI  - Multilayered heterogeneity as an intrinsic hallmark of neuroendocrine tumors.
AB  - Neuroendocrine tumors (NETs) comprise a complex and highly heterogeneous group of
      neoplasms that can arise all over the body, originating from neuroendocrine
      cells. NETs are characterized by a general lack of symptoms until they are in
      advanced phase, and early biomarkers are not as available and useful as required.
      Heterogeneity is an intrinsic, pivotal feature of NETs that derives from diverse
      causes and ultimately shapes tumor fate. The different layers that conform NET
      heterogeneity include a wide range of distinct characteristics, from the mere
      location of the tumor to its clinical and functional features, and from its
      cellular properties, to the core signaling and (epi)genetic components defining
      the molecular signature of the tumor. The importance of this heterogeneity
      resides in that it translates into a high variability among tumors and, hence,
      patients, which hinders a more precise diagnosis and prognosis and more
      efficacious treatment of these diseases. In this review, we highlight the
      significance of this heterogeneity as an intrinsic hallmark of NETs, its
      repercussion on clinical approaches and tumor management, and some of the
      possible factors associated to such heterogeneity, including epigenetic and
      genetic elements, post-transcriptional regulation, or splicing alterations.
      Notwithstanding, heterogeneity can also represent a valuable and actionable
      feature, towards improving medical approaches based on personalized medicine. We
      conclude that NETs can no longer be viewed as a single disease entity and that
      their diagnosis, prognosis and treatment must reflect and incorporate this
      heterogeneity.

PMID- 30293218
TI  - Real-world Comparative Effectiveness of Tocilizumab Monotherapy vs. Tumor
      Necrosis Factor Inhibitors with Methotrexate in Patients with Rheumatoid
      Arthritis.
AB  - INTRODUCTION: Controlled clinical studies have shown that the efficacy of
      tocilizumab (TCZ) monotherapy is superior to that of tumor necrosis factor
      inhibitor (TNFi) monotherapy and comparable to that of TCZ plus methotrexate
      (MTX) for the treatment of rheumatoid arthritis (RA). This study compared the
      real-world effectiveness of TCZ monotherapy vs. TNFis plus MTX in US patients
      with RA. METHODS: TCZ-naive patients from the Corrona RA registry with prior
      exposure to >= 1 TNFi who initiated TCZ monotherapy or TNFi + MTX were included.
      Outcomes included mean change in Clinical Disease Activity Index (CDAI),
      achievement of low disease activity (LDA; CDAI <= 10), achievement of modified
      American College of Rheumatology (mACR) 20/50 responses, and mean change in
      modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients initiating
      TNFi + MTX were grouped by MTX dose (<= 10 mg; > 10 to <= 15 mg; > 15 to <= 20
      mg; > 20 mg); outcomes in each group were compared with TCZ monotherapy using
      trimmed populations (excluding patients outside the propensity score distribution
      overlap). RESULTS: Patients in all groups experienced improvement in CDAI at 6
      months (mean change, - 6.9 to - 9.7), with no significant differences between the
      TCZ monotherapy and TNFi + MTX groups. Achievement of LDA and mACR responses at 6
      months were comparable between the TCZ monotherapy and TNFi + MTX groups;
      overall, 26.8-38.0% of patients achieved LDA, 24.3-37.6% achieved mACR20 response
      and 13.2-20.8% achieved mACR50 response. The mean change in mHAQ at 6 months was 
      0.1 in all groups. CONCLUSIONS: In this real-world population of US patients
      with RA who had prior TNFi exposure, there was no evidence of a difference in the
      effectiveness of TCZ monotherapy compared with that of TNFi + MTX, regardless of
      MTX dose, at 6 months for improving RA disease activity. FUNDING: Corrona, LLC.
      Plain language summary available for this article.

PMID- 30293219
TI  - Left upper pulmonary vein connected to the persistent left superior vena cava and
      the left atrium.
AB  - Persistent left superior vena cava (PLSVC) is the most common anomalous thoracic
      venous drainage. A PLSVC usually drains into the right atrium through a dilated
      coronary sinus. It is rare that a PLSVC flows directly into the left atrium, and
      even rarer that it connects to the left upper pulmonary vein (LUPV). We report a
      case, wherein the LUPV connected to both the PLSVC and the left atrium.

PMID- 30293221
TI  - In order to ensure that evidence is unbiased it is sometimes necessary to retreat
      to the scientific ivory tower.

PMID- 30293220
TI  - Correction to: Release of overexpressed CypB activates ERK signaling through
      CD147 binding for hepatoma cell resistance to oxidative stress.
AB  - The original version of this article contained a mistake. The bands for HA Tag
      and t-ERK in Figs. 2d, 2h, 3d are incorrect. The author informs that these errors
      had no influence in the scientific content of the paper. The corrected figures
      (Figs. 2 and 3) are given below.

PMID- 30293222
TI  - Melioidosis mimicking miliary tuberculosis.
AB  - Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a gram
      negative intracellular bacillus. Tuberculosis, also an infectious disease, is
      caused by Mycobacterium tuberculosis, an acid fast bacillus. In both diseases,
      patients commonly present with fever and respiratory symptoms due to sepsis which
      might lead to respiratory failure or sudden death if left untreated. Not only are
      these two entities similar in clinical presentation, but the autopsy findings may
      mimic each other, giving rise to difficulties in determining the cause of death.
      We report a case of melioidosis and compare it to a typical case of miliary
      tuberculosis. Similarities between the cases on gross and histopathological
      examinations are discussed. In such circumstances, microbiological culture of
      bodily fluids and internal organs should be performed to ascertain the correct
      cause of death.

PMID- 30293223
TI  - Sodium nitrite food poisoning in one family.
AB  - Sodium nitrite is used as a coloring agent or preservative in food, as well as an
      antimicrobial agent in meat and fish and some cheeses. In high amounts it can be
      toxic for humans, causing methemoglobinemia. This is an unusual and potentially
      fatal condition in which hemoglobin is oxidized to methemoglobin (MHb), reducing
      the amount of oxygen that is released from hemoglobin, similar to carbon monoxide
      poisoning. MHb levels of 70% are generally lethal, but the existence of
      underlying anemia, acidosis, respiratory compromise, and cardiac disease may
      exacerbate the toxicity of MHb. We present a case of poisoning with sodium
      nitrite in three family members after eating homemade sausages given to them by
      their neighbor who was a butcher. According to the findings of the veterinary
      inspectorate in charge of food control in this case, the concentration of sodium
      nitrite in the homemade sausages was about 3.5 g per 1 kg of meat, almost 30
      times higher than allowed according to legislation. In this case report, a 70
      year-old man died about 7 h after consuming the meal, while two women, 53 and 67
      years of age, respectively, were admitted to a toxicology clinic the following
      day due to food poisoning, with the maximum concentration of MHb in blood of 33.7
      and 20.4%, respectively. They were discharged 3 days later. The autopsy of the
      deceased man showed sodium nitrite poisoning with a relatively low concentration
      of MHb in his blood - 9.87%. Death was attributed to the exacerbation of
      hypertensive and ischemic heart disease, resulting from accidental sodium nitrite
      poisoning. The presented cases illustrate the necessity of close cooperation
      between the authorities, medical staff, veterinary inspectorate, and forensic
      pathologists in determining the source of poisoning, the cause of death of the
      victim, and preventing the outbreak of poisoning among a greater number of
      consumers.

PMID- 30293224
TI  - Knowledge, attitude, and practice of healthcare professionals toward clinically
      applying graduated compression stockings: results of a Chinese web-based survey.
AB  - This study had three objectives: (1) to investigate healthcare professionals'
      knowledge, attitude, and practice toward clinically applying graduated
      compression stockings, (2) to analyze the influencing factors, and (3) to provide
      data to support departments that develop health policies. A self-administered web
      based survey was completed by 1,444 healthcare professionals, including
      physicians and nurses from 15tertiary hospitals and four secondary hospitals from
      10 provinces in China. Reliability analysis and exploratory factor analysis were
      used to evaluate the researcher-designed questionnaire's reliability and
      validity. The formal questionnaire, which included demographic data (eight
      items), knowledge (ten items), attitudes (four items), and clinical practice
      patterns (six items), was distributed among healthcare professionals. The
      relationships and mechanisms among the variables were explored using descriptive
      statistical analysis, Pearson's correlation coefficients, and multiple linear
      regression analysis. Of the 1,444 respondents, 31.2% had good knowledge of
      clinically applying graduated compression stockings, 83.5% had a positive
      attitude toward clinically applying them, and 30.4% of respondents exhibited
      normative behavior when applying them. The multiple linear regression analysis
      indicated that training was an important factor influencing the knowledge,
      attitude, and practice toward clinically applying graduated compression
      stockings. The healthcare professionals' attitude toward clinically applying
      graduated compression stockings was positive, but the related knowledge was poor,
      and the code of behavior was deficient. Medical institutions should improve
      training for clinically applying graduated compression stockings among healthcare
      professionals and standardize the use of graduated compression stockings to
      facilitate the prevention of hospital-acquired venous thromboembolism.

PMID- 30293225
TI  - Intraocular pressure and wound state immediately after long versus short clear
      corneal incision cataract surgery.
AB  - PURPOSE: To compare the intraocular pressure (IOP) and wound state immediately
      after cataract surgery for eyes with a long clear corneal incision (CCI) with
      those for eyes with a short CCI. STUDY DESIGN: Randomized clinical trial.
      METHODS: One hundred twenty-eight eyes of 128 patients scheduled for
      phacoemulsification were randomly assigned to undergo long (>= 1.75 mm) or short
      (< 1.75 mm) CCI (2.4-mm wide). IOP was measured using a rebound tonometer
      preoperatively, at the conclusion of surgery, and at 30 min, 60 min, 120 min, 180
      min, and 24 h postoperatively. Wound architecture determined using anterior
      segment-optical coherence tomography and flare intensity was examined at 60 min
      postoperatively. RESULTS: The mean incision length was significantly longer in
      the long CCI group (2.02 +/- 0.19 mm) than in the short CCI group (1.50 +/-
      0.13mm; P < .0001). The mean IOP significantly increased at 120 min and 180 min
      postoperatively (P <= .0005) and returned to the preoperative level within 24 h.
      The mean IOP did not differ significantly between the long and short CCI groups
      at any follow-up period. The incidence of IOP lower than 10 mmHg did not differ
      significantly between the groups. The mean flare intensity was significantly
      greater in the short CCI group than in the long CCI group (P = .0122). The wound
      architecture was similar between the groups. CONCLUSION: IOP and wound
      architecture were comparable between eyes with a long CCI and eyes with a short
      CCI in the immediate postoperative periods up to 24 h, suggesting that wound
      stability is equivalent when the CCI is securely closed with wound hydration.

PMID- 30293226
TI  - Automated segmentation of en face choroidal images obtained by optical coherent
      tomography by machine learning.
AB  - PURPOSE: To develop an automated method to segment the choroidal layers of en
      face optical coherent tomography (OCT) images by machine learning. STUDY DESIGN:
      A cross-sectional, prospective study of 276 eyes of 181 healthy subjects.
      METHODS: OCT en face images of the choroid were obtained every 2.6 MUm from the
      retinal pigment epithelium (RPE) to the chorioscleral border. The images at the
      start of the choriocapillaris, start of Sattler's layer, and start of Haller's
      layer were identified, and the image numbers from the RPE line were taken as the
      teacher data. Forty-one feature quantities of each image were extracted. A
      support vector machine (SVM) model was created from each feature value of the
      training data, and a coefficient of determination was calculated for each layer
      of the choroid by a fivefold cross validation. Next, the same evaluation was
      performed after creating a SVM model with selected effective feature quantities.
      RESULTS: The mean coefficient of determination using all features was 0.9853 +/-
      0.0012. Nine effective feature quantities (relative choroid thickness,
      mean/kurtosis/variance of brightness, FFT_ skewness, k0_vessel width,
      k1/k2/k4_vessel area) were selected, and the mean of the coefficient of
      determinations with these quantities In this model was 0.9865 +/- 0.0001. The
      number of errors in the image number at the start of each layer was 1.01 +/- 0.79
      for the choriocapillaris, 1.13 +/- 1.12 for Sattler's layer, and 3.77 +/- 2.90
      for Haller's layer. CONCLUSION: Automated stratification of the choroid in en
      face images can be done with high accuracy through machine learning.

PMID- 30293227
TI  - Pediatric endocrinology: an overview of the last decade.
AB  - Over the past decade, considerable progress has been made in the field of
      pediatric endocrinology. However, there is still a long way to go regarding the
      exploration of novel avenues, such as epigenetics, the changing views on the
      pathophysiology and derived therapy of specific disorders, and the prevention of
      prevalent diseases. The next decade will hopefully bring the consolidation of
      most of those achievements and the development of new pathways for further
      progress.

PMID- 30293229
TI  - Anti-tumor effect of endostatin in a sleep-apnea mouse model with tumor.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with cancer incidence and
      mortality. The underlying mechanism is unclear. This study aims to evaluate the
      influence of intermittent hypoxia (IH), a novel hallmark of OSA, on tumor and to
      access the anti-tumor effect of endostatin on a mouse model with OSA. METHODS:
      The C57BL/6 J mice were randomly classified into four groups: control (normoxia)
      (CTL), control plus endostatin (CTL + ED), IH, and IH plus endostatin (IH + ED).
      Mice in IH and IH + ED groups were subjected to IH 8 h per day in 5 weeks. Lewis
      lung cancer cells were injected into the flank of each mouse after 1 week of IH
      exposure. Endostatin was also intraperitoneally injected after tumor volume
      reached about 200 mm3. The maximum standard uptake values (SUVmax) were detected
      by micro-positron emission tomography-computed tomography (micro-PET-CT) imaging
      prior and post-endostatin administration. Microvessel density (MVD) and vascular
      endothelial growth factor (VEGF) were determined for evaluating the anti-tumor
      effect of endostatin among the normoxia and IH conditions. RESULTS: Mice had
      higher SUVmax in the IH group than the CTL group (p < 0.01). When compared with
      mice in the CTL group, those in the IH group had significantly greater MVD values
      (p < 0.001). The SUVmax can be attenuated by endostatin both in the CTL (p <
      0.01) and IH conditions (p < 0.001). When compared with CTL group, mice in the IH
      group had increased MVD values (p < 0.001) and VEGF expression both at mRNA (p <
      0.05) and protein levels (p < 0.001 in western blotting results). Treatment with
      endostatin attenuated serum and tissue VEGF levels, lowering the MVD values. As
      compared to normoxia condition, the endostatin-therapeutic effects were more
      significant under the IH condition (p < 0.05 in western blotting results).
      CONCLUSIONS: Micro-PET-CT imaging is a promising non-invasive technique to
      evaluate the tumor metabolic characteristics under IH condition in vivo. The anti
      tumor effect of endostatin under IH condition is superior to that of the normoxia
      condition.

PMID- 30293230
TI  - A combination of hydroxytyrosol, omega-3 fatty acids and curcumin improves pain
      and inflammation among early stage breast cancer patients receiving adjuvant
      hormonal therapy: results of a pilot study.
AB  - PURPOSE: Breast cancer patients receiving hormonal therapies face risks of
      relapse, increased rates of cardiovascular events, and toxicities of therapy such
      as aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS). C
      reactive protein (CRP), a marker for inflammation, is associated with breast
      cancer outcomes. We evaluated whether the olive-derived polyphenol hydroxytyrosol
      combined with omega-3 fatty acids and curcumin would reduce CRP and
      musculoskeletal symptoms in breast cancer patients receiving adjuvant hormonal
      therapies. EXPERIMENTAL DESIGN: This prospective, multicenter, open-label, single
      arm, clinical trial enrolled post-menopausal breast cancer patients (n = 45) with
      elevated C-reactive protein (CRP) taking predominantly aromatase inhibitors to
      receive a combination of hydroxytyrosol, omega-3 fatty acids, and curcumin for 1
      month. CRP, other inflammation-associated cytokines, and pain scores on the Brief
      Pain Inventory were measured before therapy, at the end of therapy and 1 month
      after completion of therapy. RESULTS: CRP levels declined during the therapy
      [from 8.2 +/- 6.4 mg/L at baseline to 5.3 +/- 3.2 mg/L (p = 0.014) at 30 days of
      treatment], and remained decreased during the additional 1 month off therapy.
      Subjects with the highest baseline CRP levels had the greatest decrease with the
      therapy. Pain scores also decreased during the therapy. There were no significant
      adverse events. CONCLUSIONS: The combination of hydroxytyrosol, omega-3 fatty
      acids, and curcumin reduced inflammation as indicated by a reduction in CRP and
      reduced pain in patients with aromatase-induced musculoskeletal symptoms. Longer
      studies comparing this combination to other anti-inflammatories in larger groups
      of patients with clinical outcome endpoints are warranted.

PMID- 30293231
TI  - Consensus on management of castration-resistant prostate cancer on behalf of the
      Urological Tumours Working Group (URONCOR) of the Spanish Society of Radiation
      Oncology.
AB  - BACKGROUND: The knowledge in the field of castration-resistant prostate cancer
      (CRPC) is developing rapidly, with emerging new therapies and advances in
      imaging. Nonetheless, in multiple areas there is still a lack of or very limited
      evidence, and clear guidance from clinicians regarding optimal strategy is
      required. METHODS: A modified Delphi method, with 116 relevant questions divided
      into 7 different CRPC management topics, was used to develop a consensus
      statement by the URONCOR group. RESULTS: A strong consensus or unanimity was
      reached on 93% of the proposed questions. The seven topics addressed were: CRPC
      definition, symptomatic patients, diagnosis of metastasis, CRPC progression, M0
      management, M1 management and sequencing therapy, and treatment monitoring.
      CONCLUSIONS: The recommendations based on the radiation oncology experts'
      opinions are intended to provide cancer specialists with expert guidance and to
      standardise CRPC patient management in Spain, facilitating decision-making in
      different clinically relevant issues regarding CRPC patients.

PMID- 30293232
TI  - Real-world data on the efficacy and safety of weekly oral vinorelbine in breast
      cancer patients previously treated with anthracycline or taxane-based regimens.
AB  - PURPOSE: To evaluate the efficacy and safety of oral weekly vinorelbine 60 mg/m2
      for metastatic breast cancer (MBC) in patients previously treated with
      anthracyclines or taxanes in routine clinical practice. MATERIALS AND METHODS:
      Fifty-five patients were enrolled in a prospective multicentre study conducted in
      Spain. Women >= 18 years of age with locally advanced breast cancer who were not
      candidates for surgical treatment with a radical intention or patients with stage
      IV disease, and who had received a prior taxane or anthracycline regimen were
      eligible for participation. RESULTS: Median age was 67 years. Median progression
      free survival was 3.7 months (95% CI 2.5-4.9), median overall survival 10 months
      (95% CI 6.6-13.5), and overall response rate and clinical benefit rate were 29.1%
      and 49.1%, respectively. Main grade 3 and 4 toxicities were neutropenia 9.1%,
      febrile neutropenia 3.6% and constipation 3.6%. In total, 86% of the patients
      received complete treatment without delays or dose reduction. Moreover, HER2
      positive patients who received oral vinorelbine concomitantly with trastuzumab
      showed better response (complete response: HER2-positive 14.3% vs. HER2-negative
      0%; partial response: HER2-positive 42.9% vs. HER2-negative 25.6%; p = 0.008),
      better disease control rate (HER2-positive 100% vs. HER2-negative 46.2%; p =
      0.011), and better values for the remaining analysed variables than HER2-negative
      patients. CONCLUSION: Our study provides real-world data on the use of oral
      weekly vinorelbine, which proves an effective and well-tolerated regimen for MBC
      patients previously treated with taxanes or anthracyclines. Patients with HER2
      positive disease could also benefit from this treatment in combination with
      trastuzumab.

PMID- 30293233
TI  - Valproate preparations for agitation in dementia.
AB  - BACKGROUND: Agitation has been reported in up to 90% of people with dementia.
      Agitation in people with dementia worsens carer burden, increases the risk of
      injury, and adds to the need for institutionalisation. Valproate preparations
      have been used in an attempt to control agitation in dementia, but their safety
      and efficacy have been questioned. OBJECTIVES: To determine the efficacy and
      adverse effects of valproate preparations used to treat agitation in people with
      dementia, including the impact on carers. SEARCH METHODS: We searched ALOIS - the
      Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 7
      December 2017 using the terms: valproic OR valproate OR divalproex. ALOIS
      contains records from all major health care databases (the Cochrane Library,
      MEDLINE, Embase, PsycINFO, CINAHL, LILACS) as well as from many trials databases
      and grey literature sources. SELECTION CRITERIA: Randomised, placebo-controlled
      trials that assessed valproate preparations for agitation in people with
      dementia. DATA COLLECTION AND ANALYSIS: Two review authors independently screened
      the retrieved studies against the inclusion criteria and extracted data and
      assessed methodological quality of the included studies. If necessary, we
      contacted trial authors to ask for additional data, including relevant subscales,
      or for other missing information. We pooled data in meta-analyses where possible.
      This is an update of a Cochrane Review last published in 2009. We found no new
      studies for inclusion. MAIN RESULTS: The review included five studies with 430
      participants. Studies varied in the preparations of valproate, mean doses (480
      mg/day to 1000 mg/day), duration of treatment (three weeks to six weeks), and
      outcome measures used. The studies were generally well conducted although some
      methodological information was missing and one study was at high risk of
      attrition bias.The quality of evidence related to our primary efficacy outcome of
      agitation varied from moderate to very low. We found moderate-quality evidence
      from two studies that measured behaviour with the total Brief Psychiatric Rating
      Scale (BPRS) score (range 0 to 108) and with the BPRS agitation factor (range 0
      to 18). They found that there was probably little or no effect of valproate
      treatment over six weeks (total BPRS: mean difference (MD) 0.23, 95% confidence
      interval (CI) -2.14 to 2.59; 202 participants, 2 studies; BPRS agitation factor:
      MD -0.67, 95% CI -1.49 to 0.15; 202 participants, 2 studies). Very low-quality
      evidence from three studies which measured agitation with the Cohen-Mansfield
      Agitation Index (CMAI) were consistent with a lack of effect of valproate
      treatment on agitation. There was variable quality evidence on other behaviour
      outcomes reported in single studies of no difference between groups or a benefit
      for the placebo group.Three studies, which measured cognitive function using the
      Mini-Mental State Examination (MMSE), found little or no effect of valproate over
      six weeks, but we were uncertain about this result because the quality of the
      evidence was very low. Two studies that assessed functional ability using the
      Physical Self-Maintenance Scale (PSMS) (range 6 to 30) found that there was
      probably slightly worse function in the valproate-treated group, which was of
      uncertain clinical importance (MD 1.19, 95% CI 0.40 to 1.98; 203 participants, 2
      studies; moderate-quality evidence).Analysis of adverse effects and serious
      adverse events (SAE) indicated a higher incidence in valproate-treated
      participants. A meta-analysis of three studies showed that there may have been a
      higher rate of adverse effects among valproate-treated participants than among
      controls (odds ratio (OR) 2.02, 95% CI 1.30 to 3.14; 381 participants, 3 studies,
      low-quality evidence). Pooled analysis of the number of SAE for the two studies
      that reported such data indicated that participants treated with valproate
      preparations were more likely to experience SAEs (OR 4.77, 95% CI 1.00 to 22.74;
      228 participants, 2 studies), but the very low quality of the data made it
      difficult to draw any firm conclusions regarding SAEs. Individual adverse events
      that were more frequent in the valproate-treated group included sedation,
      gastrointestinal symptoms (nausea, vomiting, and diarrhoea), and urinary tract
      infections. AUTHORS' CONCLUSIONS: This updated review corroborates earlier
      findings that valproate preparations are probably ineffective in treating
      agitation in people with dementia, but are associated with a higher rate of
      adverse effects, and possibly of SAEs. On the basis of this evidence, valproate
      therapy cannot be recommended for management of agitation in dementia. Further
      research may not be justified, particularly in light of the increased risk of
      adverse effects in this often frail group of people. Research would be better
      focused on effective non-pharmacological interventions for this patient group,
      or, for those situations where medication may be needed, further investigation of
      how to use other medications as effectively and safely as possible.

PMID- 30293228
TI  - Molecular Mechanisms Mediating Diabetic Retinal Neurodegeneration: Potential
      Research Avenues and Therapeutic Targets.
AB  - Diabetic retinopathy (DR) is a devastating complication of diabetes with a
      prevalence rate of 35%, and no effective treatment options. Since the most
      visible clinical features of DR are microvascular irregularities, therapeutic
      interventions often attempt to reduce microvascular injury, but only after
      permanent retinal damage has ensued. However, recent data suggests that diabetes
      initially affects retinal neurons, leading to neurodegeneration as an early
      occurrence in DR, before onset of the more noticeable vascular abnormalities. In
      this review, we delineate the sequence of initiating events leading to retinal
      degeneration in DR, considering neuronal dysfunction as a primary event. Key
      molecular mechanisms and potential biomarkers associated with retinal neuronal
      degeneration in diabetes are discussed. In addition to glial reactivity and
      inflammation in the diabetic retina, the contribution of neurotrophic factors,
      cell adhesion molecules, apoptosis markers, and G protein signaling to
      neurodegenerative pathways warrants further investigation. These studies could
      complement recent developments in innovative treatment strategies for diabetic
      retinopathy, such as targeting retinal neuroprotection, promoting neuronal
      regeneration, and attempts to re-program other retinal cell types into functional
      neurons. Indeed, several ongoing clinical trials are currently attempting
      treatment of retinal neurodegeneration by means of such novel therapeutic
      avenues. The aim of this article is to highlight the crucial role of
      neurodegeneration in early retinopathy progression, and to review the molecular
      basis of neuronal dysfunction as a first step toward developing early therapeutic
      interventions that can prevent permanent retinal damage in diabetes.
      ClinicalTrials.gov: NCT02471651, NCT01492400.

PMID- 30293234
TI  - Occupational therapy delivered by specialists versus non-specialists for people
      with schizophrenia.
AB  - BACKGROUND: Schizophrenia is a severe mental health condition that is
      characterised by positive symptoms, such as hallucinations and delusions;
      negative symptoms, such as flattened affect, thought disorder (disrupted speech),
      and lack of motivation; and cognitive symptoms, such as problems with memory and
      attention. Schizophrenia can occur as an isolated episode, or as a recurring
      cycle of remission and relapse, and is associated with impairment in psychosocial
      and occupational functioning.Although antipsychotic drugs are the main treatment
      for people with schizophrenia, in most countries mental health services usually
      provide a range of add-on interventions, including occupational therapy. This is
      a complex intervention designed to support and enable continued participation in
      daily life through engagement in activities and occupations meaningful to the
      individual. Occupational therapists are professionals trained to deliver therapy
      where the emphasis is on improving occupational function and participation rather
      than treating symptoms, and uses a wide range of methods based on the needs of
      individuals. However, similar interventions may also be delivered by staff not
      trained as occupational therapists. OBJECTIVES: To examine the effects of
      occupational therapy delivered by occupational therapists compared to
      occupational therapy delivered by any other person for people with schizophrenia.
      SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based
      Register of Trials (including trial registers) on 4 November 2016 and 26 July
      2018. SELECTION CRITERIA: All randomised controlled trials evaluating the
      functional or clinical outcomes of occupational therapy, or both, for people with
      schizophrenia delivered by occupational therapists compared with occupational
      therapy for people with schizophrenia delivered by anyone other than occupational
      therapists. DATA COLLECTION AND ANALYSIS: Review authors independently inspected
      citations, selected studies, extracted data, and appraised study quality. MAIN
      RESULTS: The search yielded 1633 records. Of these, we retrieved 17 full-text
      reports (14 studies) for further scrutiny, which we subsequently excluded as they
      did not meet our inclusion criteria. AUTHORS' CONCLUSIONS: Currently there are no
      randomised controlled trials comparing delivery of occupational therapy for
      people diagnosed with schizophrenia by occupational therapists with delivery of
      similar interventions by anyone other than occupational therapists. Research
      studies employing methodologically robust trial designs are needed to establish
      whether or not there are better outcomes for people with a diagnosis of
      schizophrenia with occupational therapy that is delivered by trained occupational
      therapists.

PMID- 30293235
TI  - Adjacent skin rotation flap for large defect in primary breast tumor.
AB  - BACKGROUNDS: Surgical resection of large primary breast tumor often results in
      large chest wall defects. The purpose of this study is to evaluate the
      feasibility of using adjacent skin rotation (ASR) flap in patients with giant
      primary breast tumor. METHODS: A total of 26 giant primary breast tumor patients
      treated with ASR flap were included in this study. The postoperative conditions,
      including operating time, blood loss, length of hospital stay, and clinical
      complications were observed. Meanwhile, the information on 17 breast tumor
      patients treated with transverse rectus abdominis myocutaneous (TRAM) flap were
      collected and assigned to a control group. RESULTS: The mean defect size after
      mastectomy was 16.7 * 13.4 cm, while the median follow-up period was 13 months
      after surgery. A total of 15.4% patients had developed with local complications,
      and one of them had more than one complication. When comparing the postoperative
      outcomes, statistically significant differences were found between the two groups
      with respect to operating time, blood loss, and length of hospital stay (P <
      0.001). CONCLUSIONS: ASR flap is a reliable technique for immediate
      reconstruction of massive chest wall defects in patients with giant primary
      breast tumor.

PMID- 30293236
TI  - Comparing two blood culture systems for the detection of bacterial contamination
      in platelet concentrates.
AB  - BACKGROUND: The transfusion of platelet concentrates (PCs) contaminated with
      bacteria may cause serious, and even fatal, septic reactions in patients. The aim
      of this study was to compare the VersaTREK with the BACTEC FX automated culture
      systems for screening bacterial contamination, directly after the delay of 24
      hours of preparation to obtain the final pooled buffy coat PCs, to prevent
      transfusion-transmitted bacterial infections. STUDY DESIGN AND METHODS: Seven
      bacterial strains were each inoculated into five replicate pooled buffy coat PCs
      at approximately 100 colony-forming units/unit, and 5- or 10-mL samples were
      inoculated into duplicate aerobic culture bottles. The time and detection rates
      were compared between BACTEC FX, as a reference method, and VersaTREK. RESULTS:
      Time to detection was significantly shorter using VersaTREK for most species
      detected by both systems for the volumes tested. Of 70 VersaTREK cultures, 69
      (98.57% detection rate) were positive after 24 hours of incubation with the 5-mL
      sample. In contrast, the BACTEC FX system detected all positive samples in PCs
      for the volume of 10 mL, although seven samples were false negatives for the 5-mL
      volume. CONCLUSION: The VersaTREK system compared favorably to the BACTEC FX
      system for 5-mL volumes (p < 0.05) and could be considered a potential method for
      detecting bacterial contamination in PC samples directly after 24 hours of
      preparation of the final pooled buffy coat PCs.

PMID- 30293237
TI  - In-situ microbially induced Ca2+ -alginate polymeric sealant for seepage control
      in porous materials.
AB  - This paper presents a novel approach of using in-situ microbially induced Ca2+ 
      alginate polymeric sealant for seepage control in porous materials. This process
      comprises two steps: (i) generation of insoluble calcium carbonate inside the
      pores of porous materials (such as sand) through a microbially induced carbonate
      precipitation (MICP) process in-situ and (ii) injection of sodium alginate for in
      situ gelation via reaction between alginate and Ca2+ ions. The experimental
      results showed that the hydraulic conductivity/permeability of sand decreased
      with the increase in alginate concentration. When 5% alginate was used with a
      CaCO3 concentration of 0.18 g g-1 sand, the permeability of the alginate-treated
      sand reduced from 5.0 * 10-4 to 2.2 * 10-9  m s-1 . The scanning electron
      microscopy images revealed that a film-type coating was formed around sand
      particles with spherical round crystals embedded. Furthermore, the in-situ formed
      Ca-alginate polymeric sealant can also be used for the removal of Cu2+ ion and
      suspended particles from contaminated water by more than 90%. Built on the
      current research, the envisioned practical application of the proposed method may
      include clogging fractured rock, reducing seepage and prevent piping through
      dams, excavation dewatering, and forming barriers for remediating specific
      contaminants.

PMID- 30293238
TI  - Estimating contribution of rare non-coding variants to neuropsychiatric
      disorders.
AB  - Owing to recent advances in DNA sequencing technology, a number of large-scale
      comprehensive analyses of genetic variations in protein-coding regions (i.e.,
      whole-exome sequencing studies), have been conducted for neuropsychiatric and
      neurodevelopmental disorders, such as autism spectrum disorders, intellectual
      disability, and schizophrenia. These studies, especially those focusing on de
      novo (newly arising) mutations and extremely rare variants, have successfully
      identified previously unrecognized disease genes/mutations with a large effect
      size and deepen our understanding of the biology of neuropsychiatric diseases.
      Along with the continuously dropping sequencing cost, now the target of
      sequencing studies is expanding from the exome to the whole human genome. Several
      pioneering works have provided important insights into the contribution of rare
      non-coding variants to neuropsychiatric diseases. At the same time, these studies
      highlight need for further larger sample sizes and improvement in annotation of
      non-coding regulatory variants. In this review, key findings from recent studies
      as well as likely future directions are overviewed.

PMID- 30293240
TI  - Editorial Comment from Dr Takagi to Acute kidney injury and intermediate-term
      renal function after clampless partial nephrectomy.

PMID- 30293239
TI  - Short-term outcomes of pleurectomy decortication and extrapleural pneumonectomy
      in mesothelioma.
AB  - BACKGROUND/OBJECTIVES: We evaluated postoperative mortality and complications
      after extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) to
      better understand their effectiveness in malignant pleural mesothelioma (MPM).
      METHODS: A meta-analysis was done to evaluate 30-day mortality and postoperative
      complications. In addition, in-patients data of 500 eligible patients with MPM
      who underwent EPP or P/D was extracted from the New York Statewide Planning and
      Research Cooperative System (SPARCS). Multivariate analyses and propensity
      matching were used to compare in-hospital mortality and postoperative
      complications in EPP vs P/D. RESULTS: The meta-analysis showed a statistically
      significant difference in 30-day mortality (5% [95% CI: 4-6] vs P/D 2% [95% CI: 1
      3]), proportion of complications (46% [95% CI: 36-56] vs 24% [95% CI: 15-34]) and
      postoperative arrhythmias (20% [95% CI: 12-31] vs 5% [95% CI: 2-8]) for EPP vs
      P/D. In-hospital mortality (OR adj : 2.6; 95% CI: 0.86-7.75) and postoperative
      complications (OR adj : 1.1; 95% CI: 0.68-1.86) were not different in EPP
      compared with P/D while supraventricular arrhythmia was significantly more
      frequent after EPP vs P/D (OR adj : 5.2; 95% CI: 2.34-11.33). CONCLUSIONS:
      Postoperative mortality, postoperative complications, and particularly
      supraventricular arrhythmia are less frequent after P/D vs EPP. P/D, a less
      invasive surgery, may provide a better option when technically feasible for
      patients with MPM.

PMID- 30293241
TI  - Does intra-operative margin assessment improve margin status and re-excision
      rates? A population-based analysis of outcomes in breast-conserving surgery for
      ductal carcinoma in situ.
AB  - BACKGROUND AND OBJECTIVES: Using a 2 mm margin criteria, we evaluated the effect
      of intra-operative margin assessment on margin status and re-excisions following
      breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). METHODS: We
      identified patients undergoing BCS for DCIS from a prospective, population-based
      database. Multivariable logistic regression was used to determine the effect of
      specimen mammography, ultrasound and macroscopic assessment by a pathologist on
      margins and re-excision rates. RESULTS: In 588 patients, 52% (95% confidence
      interval [CI], 48%-56%) had positive margins (<2 mm), 39% (95% CI, 35%-43%) had a
      re-excision and 15% (95% CI, 12%-18%) had completion mastectomy. There were few
      re-excisions for margins >=2 mm (2%). Adjusting for confounders, any margin
      assessment versus wire localization alone did not reduce positive margins (odds
      ratio [OR], 0.75; P = 0.202) or re-excisions (OR, 1.14; P = 0.564), however both
      outcomes varied by type of technique ( P < 0.001). Individually, only macroscopic
      assessment by pathologist reduced positive margins (OR, 0.54; P = 0.002) and re
      excisions (OR, 0.61; P = 0.036). CONCLUSIONS: Despite adherence to a 2 mm margin
      criteria, re-excision rates remain high following BCS for DCIS, with 39%
      converted to mastectomy when re-excision is required. Intra-operative margin
      assessment does not appear to reduce re-excisions; in particular, surgeons should
      be aware of the limitations of specimen mammography for margin assessment in
      DCIS.

PMID- 30293242
TI  - Hypertension and diabetes mellitus are not associated with worse renal functional
      outcome after partial nephrectomy in patients with normal baseline kidney
      function.
AB  - OBJECTIVE: To analyze the association of hypertension and/or diabetes mellitus on
      renal function after partial nephrectomy in patients with normal baseline kidney
      function. METHODS: We identified 453 patients with baseline estimated glomerular
      filtration rate >=60 that underwent robotic partial nephrectomy for a cT1 renal
      mass from 2008 to 2014 using a multi-institutional database. The association
      between estimated glomerular filtration rate and time (pre-partial nephrectomy to
      24 months post-partial nephrectomy) was compared between 269 (59.4%) patients
      with preoperative hypertension and/or diabetes mellitus and 184 (40.6%) patients
      with neither hypertension nor diabetes mellitus using a multivariable model
      adjusting for confounders. RESULTS: The estimated glomerular filtration rate
      significantly decreased over time for both groups compared with baseline (average
      units/month: 1.8974 hypertension/diabetes mellitus, 1.2163 no
      hypertension/diabetes mellitus; P < 0.0001), and the estimated glomerular
      filtration rate decrease per month reduced over time (P < 0.0001). The estimated
      glomerular filtration rate began to increase at approximately 12 months for the
      hypertension/diabetes mellitus group, and at approximately 18 months for the no
      hypertension/diabetes mellitus group. Although a greater initial decline in the
      estimated glomerular filtration rate after partial nephrectomy was observed for
      the hypertension/diabetes mellitus group (0.68 units/month), this was not
      statistically significant (P = 0.0842); and while the rate of recovery from this
      decline was faster for the hypertension/diabetes mellitus group, this also was
      not statistically significant (P = 0.0653). The predicted estimated glomerular
      filtration rate was similar (83 mL/min/1.73 m2 ) for both groups 24 months after
      partial nephrectomy. CONCLUSIONS: There seems to be no significant association
      between hypertension, diabetes mellitus and renal functional outcome after
      partial nephrectomy in patients with normal baseline glomerular filtration rate.
      Renal function declines after partial nephrectomy, but then it recovers,
      irrespective of the presence of hypertension or diabetes mellitus.

PMID- 30293243
TI  - Safety and feasibility of early postmastectomy discharge and home drain care in a
      low resource setting.
AB  - BACKGROUND: Early postmastectomy discharge with a drain in place is standard
      practice in most developed countries. Its feasibility has not been evaluated in
      low resource settings like Nigeria. METHODS: Consenting patients undergoing
      mastectomy were discharged on the third postoperative day and assessed as
      outpatients for wound complications as well as their experience at home. Wound
      outcomes were compared with patients who had traditional long stay. RESULTS:
      Forty-five of the 58 patients who had a mastectomy during the study period
      participated in the early discharge program (77.6%). Of these, four patients
      (8.9%) had drain malfunction, seroma occurred in eight patients (17.8%), eight
      patients (17.8%) had wound infection, and six patients (13.3%) had flap necrosis.
      There was no readmission. Compared with long stay patients, postoperative stay
      was significantly shorter (3 vs 11 days; P < 0.01) with significant cost savings,
      while complication rates were not statistically different. All the patients in
      the early discharge group were confident operating their drains and preferred
      early discharge. Being around relatives, reduced cost, and fear of the hospital
      environment were common reasons cited for their preference. CONCLUSION: Our
      results support the implementation of an early postmastectomy discharge program
      in a low resource setting.

PMID- 30293244
TI  - Primary tumors of the hand: Functional and restorative management.
AB  - Primary malignant tumors of the hand are rare. Most cases present to clinics
      unaffiliated with cancer centers, making it incumbent on all hand surgeons to
      understand the pathology indicative of malignancy and the proper course of
      treatment of hand neoplasms. In this review, we report, based on tumor type, the
      anatomical considerations, proper management, staging, surgical approaches,
      reconstructive considerations, and long-term surveillance of primary malignant
      tumors of the hand.

PMID- 30293245
TI  - Single-stage repair of obliterated anterior urethral strictures using buccal
      mucosa graft and dorsal penile skin flap.
AB  - OBJECTIVE: To present a single-stage repair of obliterative urethral strictures
      by simultaneous use of a buccal mucosa graft and longitudinal dorsal penile skin
      flap. METHODS: Between February 2007 and October 2016, 51 patients with
      obliterative anterior urethral stricture underwent single-stage substitution
      urethroplasty. A buccal mucosa graft was harvested and fixed to the corpora
      cavernosa as the dorsal part of the neourethra, and a vascularized dorsal penile
      skin flap was created, transposed ventrally and sutured to the buccal mucosa
      graft to form ventral part of the neourethra. RESULTS: The follow-up period was
      12-129 months (mean 49 months). The mean age of the patients was 48 years (range
      15-71 years). The mean length of the obliterated urethral segment, measured
      during the operative procedure, was 5.2 cm. The etiology of strictures was:
      unknown, hypospadias and trauma in 19, 27 and five patients, respectively. Five
      patients were lost to follow up, and 46 patients were analyzed for the outcome.
      At the end of the follow-up period, recurrence of the stricture occurred in seven
      (15.2%) patients, whereas 39 (84.8%) patients did not develop stricture. An
      additional three (6.5%) patients developed fistula, resulting in overall
      successful voiding in 36 (78.3%) patients. CONCLUSIONS: A combined buccal mucosa
      graft and longitudinal dorsal penile skin flap could be a good choice for one
      stage substitution urethroplasty in complex obliterative urethral strictures,
      with an acceptable complication rate.

PMID- 30293246
TI  - Outpatient surgical care in sub-Saharan Africa: Learning points for low- and high
      income settings.

PMID- 30293247
TI  - Virtual planning and navigational technology in reconstructive surgery.
AB  - Reconstructive technologies have expanded to include the use of virtual surgical
      planning (VSP) and computer-aided design and manufacturing (CAD-CAM), and 3
      Dimensional printing. The advantages of VSP over traditional techniques are
      highlighted in many scenarios: (a) delayed reconstruction, (b) maxillary
      reconstruction, (c) placement of dental implants, and (d) precision guided
      oncology. Microsurgery is undergoing a paradigm shift with virtual planning at
      its foreground. Herein, we describe the versatile uses for CAD-CAM and key
      operative steps.

PMID- 30293248
TI  - Contribution of next generation sequencing in pediatric practice in Lebanon. A
      Study on 213 cases.
AB  - BACKGROUND: According to the Catalogue of Transmission Genetics in Arabs, less
      than half of diseases reported in Lebanese patients are mapped. In the recent
      years, Next Generation Sequencing (NGS) techniques have significantly improved
      clinical diagnosis, compared to traditional sequencing methods. METHODS: A total
      of 213 analyses by NGS (167 by whole exome sequencing (WES) and 46 by multigene
      panels tests) were performed on pediatric patients across different regions of
      Lebanon over a period of two years (December 2015-December 2017). RESULTS:
      Neurological disorders were the most frequent referral demand for both WES and
      gene panels (122/213). Pathogenic, likely pathogenic, or variants of unknown
      significance were identified in 69.5% of the WES and panel patients combined.
      Over half of the patients with such variants had an autosomal recessive disorder.
      A definite molecular diagnosis (pathogenic or likely pathogenic variants) was
      achieved in 34.1% and 47.8% of the patients studied by WES and the multigene
      panels, respectively. Thirty-three novel variants were found in the cases that
      were molecularly solved; 26 of these being identified by WES and seven by the
      multigene panels. In three consanguineous families, autosomal recessive
      inheritance of genes previously reported as showing dominant inheritance patterns
      were found. Biallelism was found in six cases, digenism in four cases, and one
      case was trigenic. CONCLUSION: Our study thus suggests that NGS tools are
      valuable for an improved clinical diagnosis, and highlights that the increased
      adoption of such techniques will significantly further improve our understanding
      of the genetic basis of inherited diseases in Lebanon.

PMID- 30293249
TI  - Accuracy of actual resected liver volume in anatomical liver resections guided by
      3-dimensional parenchymal staining using fusion indocyanine green fluorescence
      imaging.
AB  - BACKGROUND: The aim of this study was to assess the accuracy of actual resected
      liver volume (ARLV) in anatomical liver resections (ALRs) guided by 3-dimensional
      parenchymal staining using fusion indocyanine green fluorescence imaging (IGFI).
      METHODS: Patients eligible for hepatic resection were enrolled in the current
      study from January 2016 to November 2017. All patients underwent surgery planning
      based on Medical Image Three-Dimensional Visualization System (MI-3DVS) before
      the operation, in which predicted resected liver volumes (PRLVs) were calculated.
      Under 3-dimensional guidance by fusion IGFI, ALRs were performed and ARLVs were
      measured. Simple linear regression, intra-class correlation coefficient (ICC) and
      Bland-Altman analysis were used to evaluate the relationship and agreement
      between PRLV and ARLV. RESULTS: Of the 27 patients who achieved valid demarcation
      by fusion IGFI, 12 (44.4%) received hemihepatectomy, while 10 (37.0%) and five
      (18.5%) underwent sectionectomy and segmentectomy, respectively. The relationship
      and agreement between PRLV (481.37 +/- 189.47 cm3) and ARLV (450.57 +/- 205.19
      cm3) were then evaluated. The simple regression equation obtained was PRLV =
      0.874 * ARLV + 87.75 (R = 0.946; P = 0.000). Meanwhile, ARLV (ICC = 0.943)
      achieved an excellent agreement with PRLV ( P < 0.001); 25 of 27 dots were in the
      range of 95% confidence interval in Bland-Altman analysis. CONCLUSIONS: In the
      study, these findings validated the consistency between PRLV calculated by MI
      3DVS and ARLV guided by fusion IGFI, which proved that IGFI can accurately guide
      anatomical hepatectomy. Generally, fusion IGFI can provide a valid, feasible and
      accurate demarcation line, which can confer precision to hepatic resection.

PMID- 30293251
TI  - Deficiency of Sphingosine-1-Phosphate Receptor 2 (S1P2) Attenuates Bleomycin
      Induced Pulmonary Fibrosis.
AB  - Sphingosine 1-phosphate (S1P) levels are often found to be elevated in serum,
      bronchoalveolar lavage, and lung tissue of idiopathic pulmonary fibrosis patients
      and experimental mouse models. Although the roles of sphingosine kinase 1 and S1P
      receptors have been implicated in fibrosis, the underlying mechanism of fibrosis
      via Sphingosine 1-phosphate receptor 2 (S1P2) has not been fully investigated.
      Therefore, in this study, the roles of S1P2 in lung inflammation and fibrosis was
      investigated by means of a bleomycin-induced lung fibrosis model and lung
      epithelial cells. Bleomycin was found to induce lung inflammation on day 7 and
      fibrosis on day 28 of treatment. On the 7th day after bleomycin administration,
      S1P2 deficient mice exhibited significantly less pulmonary inflammation,
      including cell infiltration and pro-inflammatory cytokine induction, than the
      wild type mice. On the 28th day after bleomycin treatment, severe inflammation
      and fibrosis were observed in lung tissues from wild type mice, while lung
      tissues from S1P2 deficient mice showed less inflammation and fibrosis. Increase
      in TGF-beta1-induced extracellular matrix accumulation and epithelial-mesenchymal
      transition were inhibited by JTE-013, a S1P2 antagonist, in A549 lung epithelial
      cells. Taken together, pro-inflammatory and pro-fibrotic functions of S1P2 were
      elucidated using a bleomycin-induced fibrosis model. Notably, S1P2 was found to
      mediate epithelial-mesenchymal transition in fibrotic responses. Therefore, the
      results of this study indicate that S1P2 could be a promising therapeutic target
      for the treatment of pulmonary fibrosis.

PMID- 30293250
TI  - Ex vivo indocyanine green fluorescence imaging for the detection of lymph node
      involvement in advanced-stage ovarian cancer.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the role of
      indocyanine green (ICG) fluorescence imaging (FI) for the ex vivo detection of
      metastatic lymph nodes (LNs) in advanced stage ovarian cancer (AOC). METHODS:
      Paraffin-embedded LNs from patients included in a previous ICG-FI study (Protocol
      NCT01834469) were further assessed for fluorescence. Intravenous injection of ICG
      was delivered intraoperatively. Tumor-to-background ratios (TBRs) were
      calculated. RESULTS: A total of 675 LNs from 19 patients were analyzed. The mean
      LN number per patient was 29.3 (median: 24; range 2-77). Seventy-three LNs were
      malignant (10.8%), 602 were benign (89.2%). The mean TBR of all LNs was 1.5 (SD
      0.8). With a cut-off TBR of 1.3, the sensitivity, specificity, positive
      predictive, and negative predictive values of ICG-FI for retroperitoneal LNs were
      80%, 41%, 2.8%, and 99%, respectively. On univariate analysis, only the
      fluorescence ratio (TBR >= 1.3) was correlated with malignancy at pathology (P =
      0.03). No predictive factors of pathological LN status were found on multivariate
      analysis. CONCLUSIONS: Ex vivo ICG-FI of retroperitoneal LNs in AOC had good
      sensitivity but poor specificity. However, its high negative predictive value
      could make it an appropriate complementary tool to focus pathological analysis on
      fluorescent LNs.

PMID- 30293252
TI  - Differential Gene Expression Common to Acquired and Intrinsic Resistance to BRAF
      Inhibitor Revealed by RNA-Seq Analysis.
AB  - Melanoma cells have been shown to respond to BRAF inhibitors; however, intrinsic
      and acquired resistance limits their clinical application. In this study, we
      performed RNA-Seq analysis with BRAF inhibitor-sensitive (A375P) and -resistant
      (A375P/Mdr with acquired resistance and SK-MEL-2 with intrinsic resistance)
      melanoma cell lines, to reveal the genes and pathways potentially involved in
      intrinsic and acquired resistance to BRAF inhibitors. A total of 546
      differentially expressed genes (DEGs), including 239 up-regulated and 307 down
      regulated genes, were identified in both intrinsic and acquired resistant cells.
      Gene ontology (GO) analysis revealed that the top 10 biological processes
      associated with these genes included angiogenesis, immune response, cell
      adhesion, antigen processing and presentation, extracellular matrix organization,
      osteoblast differentiation, collagen catabolic process, viral entry into host
      cell, cell migration, and positive regulation of protein kinase B signaling. In
      addition, using the PANTHER GO classification system, we showed that the highest
      enriched GOs targeted by the 546 DEGs were responses to cellular processes
      (ontology: biological process), binding (ontology: molecular function), and cell
      subcellular localization (ontology: cellular component). Ingenuity pathway
      analysis (IPA) network analysis showed a network that was common to two BRAF
      inhibitor-resistant cells. Taken together, the present study may provide a useful
      platform to further reveal biological processes associated with BRAF inhibitor
      resistance, and present areas for therapeutic tool development to overcome BRAF
      inhibitor resistance.

PMID- 30293253
TI  - [A brandnew concept for cochlear implantation: highlight on precision, minimal
      invasion, and individualization].

PMID- 30293255
TI  - [Clinical analysis of brain abscess after endoscopic repairment of cerebrospinal
      fluid rhinorrhea].
AB  - Objective: To explore the clinical characteristics of the complication of brain
      abscesses after cerebrospinal fluid rhinorrhea repairment. Methods: A
      retrospective analysis was conducted on 149 patients undergone endoscopic
      repairment of cerebrospinal fluid rhinorrhea from October 2007 to October 2017 in
      Department of Otorhinolaryngology Head and Neck Surgery, Tianjin HuanHu Hospital.
      The clinical characteristics and treating methods of 3 brain abscess cases were
      analyzed. Results: Of the 149 patients accepted the endoscopic repairment of
      cerebrospinal fluid rhinorrhea, 3 cases were complicated with postoperative brain
      abscesses, which showed as frontal lobe abscess by strengthened head MRI. The
      incidence of abscess was 2.0%. Abscess formation time was within 10 d after
      surgery. One case was treated with antibiotic and reducing intracranial pressure,
      while other 2 cases were treated with puncture drainage. After following-up of 1
      to 24 months, these 3 cases had no recurrence of cerebrospinal fluid rhinorrhea
      or abscess. Conclusions: The complication of brain abscess formation after
      endoscopic repairment of cerebrospinal fluid rhinorrhea is more common in frontal
      lobe, which may take place within 7-10 d postoperatively. Conservative treatment
      is the first choice. Under the condition of obvious symptoms and pus cavity
      fusion, puncture drainage can be performed.

PMID- 30293254
TI  - [Screening for hotspot mutations associated with genetic hearing impairment in
      pregnant women and subsequent prenatal diagnosis in high risk pregnancies].
AB  - Objective: To screen for hotspot gene mutations associated with genetic deafness
      in Chinese pregnant women, and to perform risk assessment and prenatal diagnosis
      in high-risk families. Methods: Between November 2012 and October 2017, 26 117
      pregnant women were screened by molecular hybridization microarray for 9 hot-spot
      mutations in 4 hereditary deafness related genes (GJB2 c. 35 del G, c. 176_191
      del 16 bp, c. 235 del G, c. 299_300 del AT, GJB3 c. 538 C>T, SLC26A4 c. 2168 A>G,
      IVS 7-2 A>G, mitochondrial DNA 12S rRNA m. 1494 C>T, m. 1555 A>G). Genotype
      analysis was carried out in husbands of women carrying mutations, and prenatal
      diagnosis was carried out in the fetuses with high risk of deafness. Results:
      Among all women tested, 1 208(4.63%) were carriers of genetic deafness mutations,
      7 with hearing impairment were affected by homozygous or compound heterozygous
      mutations, 51 were mitochondrial gene mutation carriers, 103 were carriers of
      GJB3 c. 538 C>T heterozygous mutation, 1 026 were carriers of GJB2 or SLC26A4
      heterozygous mutations, and 21 carried heterozygous mutations in two genes
      simultaneously. In 394 families, the husbands accepted gene sequence testing, and
      27 in which were determined as carriers of mutations in identical genes as their
      wives. Among which, 18 families received prenatal diagnosis, and 5 fetuses were
      diagnosed as hereditary deafness. In 9 families who did not receive prenatal
      diagnosis, 1 neonate was diagnosed as compound heterozygote after delivery.
      Conclusion: In order to prevent birth defects with congenital hearing problems,
      it is effective to provide screening for hotspot mutations in pregnant women and
      to perform prenatal diagnosis on high risk pregnancies.

PMID- 30293256
TI  - [The efficacy of ansa cervicalis anterior root for unilateral recurrent laryngeal
      nerve injury].
AB  - Objective: To discuss the long-term efficacy of laryngeal reinnervation using the
      anterior root of the ansa cervicalis in the treatment of unilateral vocal fold
      paralysis (UVFP) caused by thyroid surgery. Method: From January 2010 to January
      2016, a total of 39 UVFP patients who underwent ansa cervicalis anterior root-to
      recurrent laryngeal nerve (RLN) anastomosis and who had suffered nerve
      disfunction for 6 to 24 months were enrolled as UVFP group.Another 39 age and
      gender matched normal subjects served as control group. Videostroboscopy, vocal
      function assessment (acoustic analysis, perceptual evaluation and maximum
      phonation time), and laryngeal electromyography were performed preoperatively and
      postoperatively for assessing surgery efficacy. Paired sample t test was used for
      statistical analysis. Result: Videostroboscopic reports indicated that the
      glottic closure, vocal fold edge, vocal fold position, phase symmetry and
      regularity were significantly improved in the UVFP group (P<0.01, respectively,
      postoperative vs. preoperative)and showed no statistical differences compared to
      the control group (P>0.05, respectively). Both the postoperative GRBAS assessment
      and acoustic parameters were also significantly improved in the UVFP group, Pre
      operative acoustic parameters/Post-operative acoustic parameters were 1.68+/
      0.82/0.39+/-0.27, 10.08+/-2.56/4.58+/-2.96, 0.203+/-0.216/0.018+/-0.038, 5.96+/
      1.92/17.42+/-4.11(P<0.01, respectively) and Pre-operative acoustic
      parameters/Post-operative acoustic parameters were 0.39+/-0.27/0.32+/-0.19,
      4.58+/-2.96/3.32+/-1.27, 0.018+/-0.038/0.014+/-0.027, 17.42+/-4.11/18.76+/-5.29,
      which showed no statistical differences compared to the control group (P>0.05,
      respectively). Conclusion: Delayed laryngeal reinnervation with the anterior root
      of ansa cervicalis, it can restore the physiological laryngeal phonatory function
      to the normal or a nearly normal voice quality, which is a feasible and effective
      approach for the treatment of thyroid surgery-related UVFP.

PMID- 30293257
TI  - [Application of gastric pull up and complex laryngotracheal flap to reconstruct
      the circumferencial defect after resection of the hypopharyngeal and cervical
      esophageal cancers].
AB  - Objective: To evaluate the efficacy of gastric pull-up and complex
      laryngotracheal flap in reconstruction for circumferencial defects after
      resection of hypopharyngeal and cervical esophageal cancers. Methods: A total of
      163 cases (152 males, 11 females) with circumferencial defect after resection of
      hypopharyngeal and cervical esophageal cancers received reconstructive surgeries
      by gastric pull-up (42 cases) and complex laryngo-tracheal flaps (121 cases), of
      them 115 cases simultaneously underwent unilateral neck dissection and 20 cases
      had bilateral neck dissection. Postoperative radiotherapy was used in 67 cases,
      with a dosage of 40-60 Gy. Results: There were 127 (77.9%) cases with positive
      metastatic lymph nodes. Of 42 patients with gastric pull-up reconstruction, 39
      cases (92.8%) recovered the function of oral swallowing after operation, and 8
      cases with cervical esophageal cancer recovered the functions of oral swallowing
      and speech after gastroesophageal anastomosis reconstruction. There were 3 (7.1%)
      cases died of surgery and 8 cases with surgical complications. Reconstruction of
      upper digestive tract with combined laryngotracheal flap was successful in all
      121 cases, with recovered oral swallowing function after operation. No patient
      died of surgery but 24 cases had complications, mainly pharynx skin fistula or
      wound infection, which were cured by conservative treatments. The 1-, 3- and 5
      year survival rates for 163 patients were 69.8%, 50.5% and 34.3%, respectively.
      The independent factors for prognosis included T4 (P<0.001) and N+ (P=0.042).
      Conclusions: The complex of laryngotracheal flap with pectoralis major
      myocutaneous flap is suitable for most advanced hypopharyngeal cancer after
      resection of the tumor and reconstruction of circumferencial defect. It is simple
      technology, low and slight complication rate. The minority is not suitable for
      the application of pectoralis major myocutaneous flap can be used instead of free
      anterolateral thigh flap. Gastric pull-up for reconstruction of upper digestive
      tract is suitable for most patients with cervical esophageal cancer and
      hypopharyngeal carcinoma invading the cervical esophagus who are not suitable for
      laryngotracheal flap reconstruction, with good swallowing function after surgery.
      However, it is prudent to choose operative indications because of serious
      surgical trauma and risks for complications.

PMID- 30293258
TI  - [Clinical characteristic and prognostic analyses of 117 cases of head and neck
      mucosal melanoma].
AB  - Objective: To study the clinical characteristics of mucosal melanoma in the head
      and neck, including the risk factors affecting distant metastasis, recurrence and
      survival rate, and to provide the basis for the individualized treatment of
      mucosal melanoma in the head and neck. Methods: The clinical data of 117 cases of
      mucosal melanoma in the head and neck treated from January 2004 to June 2016 in
      Beijing Tongren Hospital were analyzed retrospectively, and the risk factors
      affecting the prognosis, distant metastasis and local recurrence were
      analyzed.Kaplan-Meier analysis was used for survival analysis, and Log-Rank test
      was used for comparison between groups. Results: The follow-up time was 5-139
      months, with a median of 32 months, and the median survival time was 34
      months.The 3 and 5 year cumulative survival rates were 47.0% and 25.0%,
      respectively.Local recurrence occurred in 27 patients (23.1%), and distant
      metastasis in 37 cases (31.6%). After the operation, 50 patients received
      radiotherapy.Multiple factor Cox regression analysis showed that distant
      metastasis, AJCC staging, and two operations were risk factors affecting survival
      (P<0.05), and immunologic/targeted therapy was a protective factor affecting
      survival prognosis(P=0.008). Postoperative radiotherapy and distant metastasis
      were important factors affecting recurrence (P<0.05). AJCC staging, pigmentation,
      and postoperative recurrence were risk factors for distant metastasis (P<0.05).
      Conclusion: The 3 and 5 year survival rates of primary mucosal melanoma in head
      and neck are low, and the incidence of local recurrence and distant metastasis
      are high. Surgery is the first choice and the integrity of the initial operation
      has an important impact on the prognosis of the patients. Postoperative adjuvant
      radiotherapy is recommended to improve the local control rate, and immunotherapy
      and targeted therapy should be applied in time to improve survival.

PMID- 30293259
TI  - [Experimental study on dendritic cells modified by dust mite allergen gene in the
      treatment of allergic rhinitis in mouse].
AB  - Objective: To explore the therapeutic effects of dendritic cells (DC) modified by
      the dust-mite-allergen(Der p1) gene on mouse model of allergic rhinitis (AR).
      Methods: DC modified by the Der p1 gene (Der p1-DC) were prepared.Using random
      number table, 24 Balb?c mice were divided into four groups: immature DC (imDC)/AR
      group, dexamethasone/AR group, Der p1-DC/AR group and control group, with 6 mice
      in each group.AR mouse model was built with Der p1 and the mouse model of AR was
      established.The AR mice were respectively given by abdominal injection of Der p1
      DC, imDC and dexamethasone.Normal control mice were treated with physiologic
      saline.ELISA method was used for determining the content of IgE, IgG1and
      histamine in blood.The relative expression of mRNA of IL-4 and IL-13 on nasal
      mucosa with protein was analyzed by RT-PCR and Westen blot methods.All the data
      were statistically analyzed by SPSS 19.0 statistical software, and the variance
      analysis was used in multiple groups of average samples. Results: The contents of
      IgE, IgG1 and histamine in the mice of Der p1-DC/AR group were lower than those
      in imDC/AR group ((0.560+/-0.110) OD 450 nm vs (1.150+/-0.280) OD 450 nm,
      (0.690+/-0.054) OD 450 nm vs (0.920+/-0.125) OD 450 nm, (4 145+/-670) pg/ml vs (7
      685+/-669) pg/ml, t value was 4.80, 4.14, 9.16, respectively, all P<0.05), and
      the expression of IL-4 and IL-13 on nasal mucosa in Der p1-DC/AR group was
      remarkedly lower than those in imDC/AR group (0.41+/-0.25 vs 1.59+/-1.02, 0.26+/
      0.01 vs 1.10+/-0.09, t value was 2.75, 22.72, respectively, all P<0.05). There
      was no statistically significant difference between the mice treated with Der p1
      DC and dexamethasone group. Conclusions: The results showed that Der p1-DC could
      reduce inflammation in AR mice and decrease the expression of IL-4 and IL-13. It
      suggested that Der p1-DC can be used in the immunotherapy of AR mouse.

PMID- 30293260
TI  - [Impact of blood eosinophils on clinical effect of endoscopic sinus surgery for
      chronic rhinosinusitis with nasal polyps].
AB  - Objective: To investigate the effect of blood eosinophils on clinical effect of
      endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps (CRSwNP).
      Methods: From March 2011 to March 2016, 72 cases with CRSwNP were treated by
      endoscopic sinus surgery in Department of Otorhinolaryngology Head and Neck
      Surgery, Peking University People's Hospital. The clinical records were
      retrospectively reviewed, and the cases were divided into eosinophilia elevated
      and non-elevated group according to blood eosinophils, and nasal polyps were
      evaluated for histopathology eosinophil count. Statistical analysis was performed
      to compare two groups' pre- and post-operative symptoms of VAS score, sinus
      computed tomography (CT) scans scores according to the Lund-Mackay system and the
      outcome of surgery. Both groups' factors that might have affected their outcome
      were analyzed by t-test, Chi square, Pearson Correlation Coefficient and
      Willcoxon rank sum test. Results: Seventy two cases were followed up from 24 to
      78 months.The average follow-up time was 56 months. The VAS score in the
      eosinophilia elevated group (n=16) was higher than that in the non-elevated
      group(n=56), and the difference was statistically significant (11.44+/-7.13 vs
      4.98+/-5.64, t=3.726, P<0.05). The control of symptoms in the peripheral blood
      eosinophilia elevated group was less than that in the non-elevated group, and the
      difference was statistically significant (Z=-1.979, P<0.05). There was a positive
      correlation between eosinophil counts in peripheral blood and tissues of 72 cases
      (r=0.429, P<0.05). Conclusion: There is a significant correlation between tissue
      and blood eosinophil counts, and eosinophilia group has poorer outcomes.

PMID- 30293262
TI  - [Two cases of intracranial complications of acute sinusitis].

PMID- 30293261
TI  - [Clinical analysis of malignant salivary gland tumors of the larynx].
AB  - Objective: To evaluate the clinical features, treatments and prognoses of
      malignant salivary gland tumors of the larynx. Methods: A total of 14 patients
      with malignant salivary gland tumors of the larynx diagnosed and treated in our
      hospital between 2003 and 2014 were analyzed retrospectively, and were compared
      with 62 patients from the Surveillance, Epidemiology, and End Results: (SEER)
      database of American for survival rates. Results Among 14 patients from our
      hospital, 9 males and 5 females, with a median of 66.5 years old; 8 patients with
      adenoid cystic carcinoma, 4 with mucoepidermoid carcinoma and 2 with
      adenocarcinoma; supraglottic, glottic and 4 subglottic malignancies respectively
      accounting for 5, 5 and 4 cases; 8 cases treated with surgery, 5 with surgery and
      postoperative radiotherapy and/or chemotherapy, and 1 with radiotherapy alone.
      The 14 patients showed a three-year overall survival rate of 50.0% and a five
      year overall survival rate of 42.9%, respectively in contrast with the rates of
      67.1% and 59.8% in SEER database. Conclusions: The malignant salivary gland tumor
      of the larynx is rare and it is difficult to be diagnosed early. It is more
      likely to occour local recurrence and distant metastasis. Extensive surgical
      resection with postoperative radiotherapy is advocated.

PMID- 30293263
TI  - [A case of esophagus foreign body misdiagnosed as foreign body aspiration].

PMID- 30293264
TI  - [Sudden asphyxia of foreign body in trachea and bronchus: experience from 3
      cases].

PMID- 30293265
TI  - [Reconstruction of the defect of hypopharyngeal carcinoma with radial forearm
      free flap without cephalic drainage: one case report].

PMID- 30293266
TI  - [One case of nasal angiomyolipoma].

PMID- 30293267
TI  - [Double-site ectopic thyroid: a case report].

PMID- 30293268
TI  - [Intra-thyroid thyroglossal duct cyst: a case report].

PMID- 30293269
TI  - [Research progress of the cholesteatoma and proliferation pathways].
AB  - Cholesteatoma is an abnormal formation of benign cystic lesions from the squamous
      epithelium of the temporal bone, and the local invasive growth could damage the
      structures of middle ear. Cholesteatoma has been the research focus in
      otorhinolaryngology, however the pathogenesis of it is still unclear. From the
      previous studies we found that the epidermal proliferation was one of the
      important factors in the pathogenesis of the cholesteatoma, which was also
      involved in multiple proliferation pathways. In this paper, we briefly reviewed
      the progress and the mechanisms of the actions of cholesteatoma in these
      pathways.

PMID- 30293270
TI  - [Complementary and alternative medicine for rhinitis and sinusitis].
AB  - Complementary and alternative medicine (CAM) describes a broad category of
      practices and treatments for the prevention or treatment of disease outside the
      realm of conventional medicine. CAM is widely used in the treatment of allergic
      rhinitis, acute and chronic rhinosinusitis. This article summarizes a variety of
      CAM and the efficacy in the treatment of rhinitis and sinusitis, with the purpose
      of increasing people's awareness of CAM and enriching the treatment of rhinitis
      and sinusitis, so that patients can benefit from it.

PMID- 30293271
TI  - [Laryngeal clefts: a review of current literature].
AB  - Laryngeal clefts as exceptionally rare congenital anomalies have been reported
      more and more recently. The clinical symptoms and presentations base on degree of
      clefts and variety of comorbidities. Mild types of clefts may have minimal
      clinical impact, whereas severe types may be life-threatening and even lead to
      death before diagnosis. With more attention of these anomalies and advances in
      endoscopy, the diagnosis, evaluation and surgery of laryngeal clefts have
      acquired great improvement, especially International Pediatric Otolaryngology
      Group(IPOG)have reported consensus guidelines on the diagnosis and management of
      type I laryngeal clefts in 2017. This review of laryngeal clefts may be
      beneficial to decrease missed diagnosis or misdiagnosis and to achieve individual
      based treatment.

PMID- 30293273
TI  - [Initiation of a crucial campaign for prevention and control of beta-thalassemia
      major].

PMID- 30293272
TI  - [Interpretation of the fourth edition of WHO pathological classification of the
      thyroid tumors in 2017].
AB  - In recent years, the incidence of thyroid carcinoma gradually increased in China.
      The pathology diagnosis and classification was based on WHO classification of
      Tumors of Endocrine Organs, the third edition which published in 2004. The fourth
      edition, WHO classification of Tumors of Endocrine Organs was published in July
      2017. Compared with the third, some important aspects (or points) were revised:
      the ICD-O code of hyalinizing trabecular tumor was changed from 0 to 1; three
      other encapsulated follicular-patterned thyroid tumors were added; the variants
      of well differentiation thyroid carcinoma (including papillary carcinoma and
      follicular carcinoma ) which was originated from thyroid epithelial cells were
      updated; oncocytic cell tumors were separated from follicular tumors; the ICD-O
      code of ectopic thymoma was changed from 1 to 3. Refinement and standardization
      part of the concepts and diagnostic criterias were done which can solve practical
      problems in pathology diagnosis.

PMID- 30293274
TI  - [Guidelines for diagnosis and treatment of beta-thalassemia major (2017)].

PMID- 30293275
TI  - [A long-term follow-up study of 82 children with acute myeloid leukemia].
AB  - Objective: To investigate the efficacy and the prognostic factors of Chinese
      Academy of Medical Sciences 2005 (CAMS-2005) regimen in the treatment of
      pediatric acute myeloid leukemia (AML). Methods: Eighty-eight cases of newly
      diagnosed AML patients, who were treated with the CAMS-2005 regimen from April
      2005 to July 2009, were enrolled in this case observational study. Clinical
      characteristics, long-term prognosis and prognostic factors were analyzed
      retrospectively. Overall survival (OS) and event free survival (EFS) rates were
      estimated by the Kaplan-Meier method. Rates of survival between the groups were
      compared by the Log-rank test. Prognostic factors were evaluated by COX
      regression analysis. Results: A total of 82 cases were enrolled in this study,
      including 34 core binding factor(CBF)-AML patients and 48 non-CBF-AML patients.
      There were 45 males and 37 females. The median age at diagnosis was 8.0 (0.7
      16.0) years. During the induction therapy, 3 patients (4%) developed treatment
      related early-death, while 63 patients (77%) achieved complete remission (CR) and
      53 patients (65%) achieved CR after 1 course. Twenty-one patients (33%) had
      relapsed disease. The CR rates of CBF-AML patients and non-CBF-AML patients were
      91% (31/34) and 67% (32/48) (chi(2)=5.410, P=0.020) , while the relapse rates
      were 29% (9/31) and 38% (12/32) (chi(2)=0.508, P=0.476) . The 8-year OS and EFS
      rates of all 82 patients were 59%(48/82) and 51%(42/82). The 8-year OS rates of
      CBF-AML patients and non-CBF-AML patients were 74% (25/34) and 48%(23/48)
      (chi(2)=5.812, P=0.016), while the 8-year EFS rates of CBF-AML patients and non
      CBF-AML patients were 71%(24/34) and 38%(18/48) (chi(2)=8.682, P=0.003). There
      were statistically significant differences between groups. The 8-year OS rates of
      patients who achieved CR after 1 course and other patients were 68% (36/53) and
      46% (12/26) (chi(2)=9.606, P=0.002), while the 8-year EFS rates were 66% (35/53)
      and 27% (7/26) (chi(2)=19.471, P=0.000), the differences were all statistically
      significant. COX multivariate analysis showed that CBF-AML or non-CBF-AML and
      whether achieved CR after 1 course were independent prognostic factors of OS
      rates (relative risk: 2.538, 2.561) and EFS rates (relative risk: 3.050, 3.686)
      (P <0.05). Conclusions: The efficacy of the CAMS-2005 regimen in the treatment of
      AML patients was well. CBF-AML or non-CBF-AML and whether achieved CR after 1
      course were independent prognostic factors for pediatric AML patients.

PMID- 30293276
TI  - [Expression and significance of programmed cell death ligand-1 in neuroblastoma
      tissues].
AB  - Objective: To investigate the relationship between expression of programmed cell
      death ligand-1(PD-L1) in the tissue of neuroblastoma (NB) and patient's clinical
      characteristics and prognosis. Methods: Clinical data and surgical tissue
      paraffin blocks of 100 newly diagnosed NB children at Sun Yat-sen University
      Cancer Center between January 2000 and December 2015 were collected and the
      expression level of PD-L1 and its' relationship with pathological parameters and
      survival rate were analyzed retrospectively. The ratio between groups was
      compared by chi-square test. Kaplan-Meier method was used for survival analysis
      and COX regression model was used for multivariate analysis. Results: Among 100
      cases, 71 were males and 29 females; there were 5 cases of stageI, 4 cases of
      stageII, 19 cases of stage III, 65 cases of stage IV and 7 cases of stage IVs.
      Ten out of 62 cases (16%) were N-MYC amplified; 15 cases were in low-risk group,
      18 were in medium-risk group and 67 were in high-risk group. The positive rate of
      PD-L1 in NB tumor tissue was 57% (57/100), of which 55 were weakly positive, 1
      was moderately positive and 1 was strongly positive. The positive rates of PD-L1
      expression in tumor tissues without bone metastasis were higher than those with
      bone metastasis(66%(39/59)vs.44%(18/41), chi(2)=4.864, P=0.027), the positive
      rates of PD-L1 expression in tumor tissues pathologically diagnosed as
      neuroblastoma were higher than those pathologically diagnosed as
      ganglioneuroblastoma (61%(53/87) vs.31%(4/13), chi(2)=4.195, P=0.041), the
      positive rates of PD-L1 expression in tumor tissues originated from abdominal
      cavity were higher than those originated from other places (61%
      (51/83)vs.35%(6/17), chi(2)=3.937,P=0.047).The 4-year event-free survival (EFS)
      rates of patients with PD-L1 negative and positive were 40% and 33%
      (chi(2)=0.009, P=0.923), respectively. The 4-year overall survival (OS) rates of
      patients with PD-L1 negative and positive were 62% and 58% (chi(2)=0.294,
      P=0.587). Among 33 non-high-risk patients, the 4-year EFS rates of patients with
      PD-L1 negative and positive were 89% and 78% (chi(2)=0.001, P=0.965), the 4-year
      OS rates of patients with PD-L1 negative and positive were 100% and 96%
      (chi(2)=0.500, P=0.480). Among 67 high-risk patients, the 4-year EFS rates of
      patients with PD-L1 negative and positive were 24% and 11% (chi(2)=1.154,
      P=0.282), the 4-year OS rates of patients with PD-L1 negative and positive were
      48% and 41% (chi(2)=0.692, P=0.405). Multivariate analysis showed that N-MYC gene
      amplification was an independent adverse prognostic factor for OS and EFS rates
      of NB patients (RR: 1.726,95%CI:1.209-2.466; RR:1.326,95%CI:1.014-1.736) and
      advanced clinical stage was an independent adverse prognostic factor for EFS
      rates of NB patients (RR: 26.498, 95%CI:3.518-199.614). Conclusions: The
      expression of PD-L1 in NB tumor tissues was correlated with the clinical
      characteristics of children. However, there were no significant differences in
      the prognosis of patients with or without PD-L1 expression.

PMID- 30293277
TI  - [Analysis of the arthropathies on no-bleeding history joints in pre-school age
      severe hemophilia A children].
AB  - Objective: To detect the arthropathies on no bleeding history joints in pre
      school hemophilia A children in order to provide evidence for further prevention
      and control of joint disease in children with hemophilia A. Methods: This study
      was a cross-sectional study based on China Hemophilia Individualized prophylaxis
      study (CHIPS). The basic data of outpatients with hemophilia in Beijing
      Children's Hospital and Chengdu Women's and Children's Central Hospital between
      August 2016 and June 2017 were collected and a three-month follow-up was
      conducted. The target joints (six joints of bilateral elbows, knees and ankles)
      of thirty-four children aged 1-7 years old with severe hemophilia A were examined
      by ultrasound, X-ray and joint function examination (4-7 years old, hemophilia
      joint health score (HJHS)). To find out whether there are arthropathies in
      patient's joints with no bleeding history and analyze the relevant factors by chi
      square test, rank sum test and other statistical methods. Results: There were 32
      analyzable cases with 112 no-bleeding history target joints, 42.9% (48/112) were
      elbow joints. Arthropathies were revealed in 34.8% (39/112) of them by joint
      structural and functional examination and 46.2% (18/39) were ankles
      (chi(2)=8.379, P=0.015) . Ultrasound showed abnormalities in 18.3% (20/109)
      joints, X-ray showed abnormalities in 3.8% (3/79) joints and HJHS showed
      abnormalities in 25.3% (20/79) joints. There was no correlation between
      ultrasound and HJHS (r=0.015, P=0.895), no correlation was found between X-ray
      and HJHS (r=-0.101, P=0.390) either, which suggested that joint structural and
      functional examination could not replace each other. The related risk factors of
      arthropathies in this group were >4.91 years old (OR=3.917, 95%CI:1.610-9.528)
      and combining with target joint (OR=3.530, 95%CI:1.316-9.465). Conclusions:
      Detecting the joint structure and function on no bleeding history joints in pre
      school hemophilia A children could reveal the arthropathies and majority of them
      were ankle arthropathies. Joint structural and functional examinations could not
      replace each other. For patients more than 5 years old and those with target
      joints, the joints with no complaint of bleeding should be examined regularly to
      reveal the arthropathies in time.

PMID- 30293278
TI  - [A national epidemiological survey on obesity of children under seven years of
      age in nine cities of China in 2016].
AB  - Objective: To investigate the prevalence and risk factors of obesity in 2016 and
      to determine secular trend of the prevalence between 1986 and 2016 among Chinese
      children under seven years of age. Methods: Data of a total of 110 485 children
      from 1 month to 7 years of age were collected by stratified-clustered-random
      sampling method in the nine cities (including northern China (Beijing, Harbin,
      Xi'an), Central (Shanghai, Nanjing, Wuhan), Southern (Guangzhou, Fuzhou,
      Kunming)) from June to November in 2016. Overweight and obesity were defined by
      the weight for height of the American National Center for Health Statistics/World
      Health Organization (NCHS/WHO) reference and be over 10% as overweight and over
      20% as obesity (20%-29% as mild, 30%-49% as moderate and over 50% as severe). The
      normal children were matched with obese children in sex, age and height in the
      case-control designs and the data were analyzed by chi(2) test and conditional
      Logistic regression model. Results: (1) The overall overweight prevalence was
      8.4% (9 317/110 485) with boys 8.4% (4 843/57 917) and girls 8.5% (4 474/52 568)
      and the overall obesity prevalence was 4.2% (4 712/110 485) with boys 4.9% (2
      860/57 917) and girls 3.6% (1 852/52 568). The obesity prevalence was
      significantly different across age groups (chi(2)=3 777.586, P<0.01), the lowest
      0.9% (144/16 380) (boys 1.1% (97/8 668), girls 0.6% (47/7 712)) at 1-<2 year and
      the highest 11.3% (1 248/11 072) (boys 14.0% (822/5 861), girls 8.2% (426/5 211))
      at 6-<7 years. The overall obesity prevalence was 4.6% (2 534/54 970) for
      suburban rural children and 4.0% (2 178/55 515) for urban children. The overall
      obesity prevalence in northern, central and southern China was 4.7% (1 985/42
      294), 4.4% (1 543/35 260) and 3.6% (1 184/32 931) respectively. The mild obesity
      prevalence was 2.8% (3 146/110 485) and the moderate 1.1% (1 272/110 485) and
      severe obesity 0.3% (294/110 485). (2) To ensure data comparability, the 2016
      urban data were compared with the previous survey urban data. Compared with the
      1986 and 2006 survey data, the obesity prevalence increased from 0.9% (660/71
      420) and 3.8%(2 227/59 302) to 4.6% (1 341/29 054) for boys, from 0.9% (596/66
      609) and 2.5%(1 323/53 643) to 3.1% (837/26 461) for girls. The increase in
      prevalence of obesity mainly appeared after 3 years of age. The obesity
      prevalence among north, central and south China increased from 1.8% (562/31 301)
      and 3.2% (1 137/35 439) to 4.2% (864/20 372), from 0.9% (464/52 138) and 3.9%(1
      412/37 031) to 4.2% (764/18 485), from 0.4% (230/54 590) and 2.5% (1 001/40 475)
      to 3.4% (550/16 658) when compared with 1986 and 2006. (3) Multivariate Logistic
      regression analysis showed that high birth weight (odds ratio (OR)=1.559 (1.038
      2.343), chi(2)=4.580, P<0.05), cesarean section (OR=1.651 (1.230-2.216),
      chi(2)=11.132, P<0.01), gestational diabetes (OR=3.364 (1.406-8.047),
      chi(2)=7.433, P<0.01), father overweight (OR=1.935 (1.417-2.642), chi(2)=17.267,
      P<0.01) or father obesity (OR=3.580 (2.304-5.561), chi(2)=32.196, P<0.01), mother
      overweight (OR=2.305 (1.611-3.298), chi(2)=20.854, P<0.01) or mother obesity
      (OR=5.232 (2.751-9.949), chi(2)=25.462, P<0.01), good appetite (OR=8.313 (5.385
      12.833), chi(2)=91.403, P<0.01), eating fast (OR=6.359 (4.539-9.010),
      chi(2)=112.513, P<0.01), eating shortly before sleeping (OR=1.553 (1.113-2.166),
      chi(2)=6.707, P<0.01), long screen watching duration (2-<3 hours: OR=1.973 (1.423
      2.736), chi(2)=16.594, P<0.01 or >=3 hours: OR=2.275 (1.413-3.661),
      chi(2)=11.448, P<0.01), short night sleep duration (8-<9 h/day) (OR=1.600 (1.074
      2.385), chi(2)=5.331, P<0.05), low education of mother (OR=1.589 (1.298-1.945),
      chi(2)=20.174, P<0.01) may be risk factors for children's obesity; moderate and
      excessive outdoor activities (e.g. running, jumping) may be protective factors
      against obesity (OR=0.540 (0.342-0.853), chi(2)=6.990, P<0.01). Conclusions: In
      recent ten years the rapidly increasing trend of children obesity has not been
      effectively curbed and there has been a new situation in the obesity prevalence
      of suburban rural children exceeding urban children. The key roles of mother in
      the early growth and development and family in the formation of good behavior
      habits of their children should be paid attention to, and family-based obesity
      prevention and control strategies for preschool children should be developed and
      improved to correct unhealthy family sharing environment and children's
      lifestyle.

PMID- 30293279
TI  - [Interleukin-10 receptor gene mutations induced very early onset inflammatory
      bowel disease in 6 infants].
AB  - Objective: To analyze the clinical features and interleukin-10 receptor gene
      mutations in six infants with very early onset inflammatory bowel disease (VEO
      IBD). Methods: Four girls and two boys with VEO-IBD admitted to Children's
      Hospital Affiliated to Capital Institute of Pediatrics from June 2016 to
      September 2017 were reviewed. The clinical data including general condition,
      clinical symptoms, laboratory tests, and colonoscopy and pathological results
      were collected and analyzed. Interleukin-10 receptor alpha subunit (IL-10RA) gene
      was examined in all patients. Results: Persistent diarrhea and fever were the
      most common symptoms and were found within 1 month after birth in all 6 patients.
      Anemia, oral ulcer or perianal lesions and growth retardation were common
      concomitant symptoms. All patients had colonoscopy examination and the results
      showed multiple ulcers affecting the colon with biopsies revealing acute and
      chronic inflammation. Three patients were found to have cryptitis and crypt
      abscesses. Gene sequencing revealed IL-10RA gene mutations in all six patients,
      including 3 cases with homozygous mutations (one with c.537G>A and two with
      c.301C>T) and 3 heterozygous mutations (paternal c.301C>T in all cases; maternal
      c.299T>G, c.350G>A and c.537G>A, respectively) . After conventional treatment,
      one got clinical and pathological improvement according to colonoscopy, three
      improved clinically, one worsened and died, and one died of septic shock
      secondary to intestinal perforation. Conclusions: VEO-IBD is associated with IL
      10RA mutation, usually with severe intestinal symptoms and significant extra
      intestinal symptoms, as well as varied responses to conventional treatment. In
      our study, c.301C>T and c.537G>A are the most common mutations.

PMID- 30293280
TI  - [Clinical and pathological features of 13 children with Epstein-Barr virus
      positive lymphoproliferative disease].
AB  - Objective: To summarize the clinical characteristics, virological and
      histopathological features, clinical outcome of Epstein-Barr virus-positive
      lymphoproliferative disease (EBV(+)LPD) in children. Methods: The clinical and
      follow-up data of 13 children histopathologically diagnosed as EBV(+)LPD in the
      Department of Infectious Disease of Beijing Children's Hospital between January
      2011 and December 2016 were summarized. Results: Of the 13 patients, 5 were males
      and 8 females. The median age of disease onset was 6.0 years (range 1.3 to 15.0
      years). The median duration between disease onset and diagnosis was 3 months
      (range 1 to 24 months). All the 13 patients had fever, 9 cases had
      hepatosplenomegaly and lymphoadenopathy, 4 cases had only lymphoadenopathy, 7
      cases had reduced peripheral blood cells, 7 cases had lung involvement, 3 cases
      had central nervous system involvement, 3 cases had cardiac involvement, 3 cases
      had intestinal involvement, 2 cases had skin involvement and 1 case had abdominal
      mass. All the 13 patients underwent whole blood EBV-DNA PCR examination and the
      copies ranged from 1*10(8)/L to 1*10(11)/L. Pathology of lymph node confirmed 6
      cases, skin pathology confirmed 2 cases, lung pathology, ileum mucosa pathology,
      liver pathology, abdominal mass pathology and bone marrow pathology confirmed 1
      case each. Among 13 patients, 9 cases presented with EBV-positive T cell
      lymphoproliferative disease(EBV(+) T-LPD), 2 cases with hydroa vacciniforme (HV)
      and 2 cases with EBV-positive diffuse large B-cell lymphoma (EBV(+) DLBCL) . All
      the patients were followed up for 2 days to 65 months after discharge. Among 9
      cases of EBV(+)T-LPD, 1 case died in a short time, 1 case died after evolved to T
      cell lymphoma, 2 cases recovered after hematopoietic stem cell transplantation, 1
      case recovered after the chemotherapy of hemophagocytic lymphohistiocytosis(HLH)
      2004 protocol and 4 cases were stable now. Of 2 cases of HV patients, 1 case died
      after evolved to HV like lymphoma and the other still have symptoms. Among 2
      cases of EBV(+) DLBCL, 1 case died shortly after discharge and the other was
      still stable after chemotherapy. Conclusions: Chronic recurrent fever,
      lymphadenopathy and hepatosplenomegaly are the most common clinical
      manifestations in children with EBV(+)LPD. Involvement of lung, central nervous
      system, intestinal tract, skin and other organs are also involved frequently. For
      children with chronic fever of unknown cause and accompanied by lymphadenopathy
      and (or) hepatosplenomegaly, EBV (+) LPD should be considered highly when the
      whole blood EBV-DNA load continues to increase significantly, early biopsy of the
      proliferative lesion should be performed to make a definite diagnosis. The
      prognosis of EBV (+) LPD is poor, and some evolve to lymphoma, hematopoietic stem
      cell transplantation is an effective way to treat this disease.

PMID- 30293281
TI  - [Diagnosis and treatment of five neonatal cerebral venous sinus thrombosis].
AB  - Objective: To summarize the clinical presentations and imaging features of
      cerebral venous sinus thrombosis (CVST) in 5 newborns. Methods: The clinical data
      of 5 newborns with CVST admitted to Department of Neonatology of Maternal and
      Children Hospital of Hubei Province from February 2017 to April 2018 were
      analyzed retrospectively. The risk factors, clinical presentations, imaging
      manifestations and treatment of CVST were investigated. Results: Of the 5 full
      term neonates, 4 were males and 1 female, with 4 aged less than 7 days and 1 more
      than 7 days; one with the history of maternal gestational diabetes mellitus, one
      with maternal gestational hypertension. The clinical presentations included
      seizures (3 cases), fever (3 cases), dehydration (1 cases), lethargy (2 cases),
      hypoglycemia (2 cases), thrombocytopenia (2 cases). Electroencephalogram (EEG)
      showed electrical seizures in 3 cases. Magnetic resonance imaging (MRI) and
      magnetic resonance venography (MRV) showed 4 cases of intracranial hemorrhage, 3
      cases of cerebral parenchymal infarction. For the sites of the thrombi, 4 were in
      the superior sagittal sinus, 3 in straight sinus, 2 in transverse sinus and 1 in
      sinus confluence. CT showed intracranial hemorrhage in 2 cases and venous sinus
      dilatation in 2 cases. Doppler ultrasound showed 2 cases of intraventricular
      hemorrhage and 2 cases of changes of venous sinus blood flow. Three neonates were
      treated with anticoagulant and thrombolytic therapy, followed by recanalization
      of the veins and discontinuing of seizures. Conclusions: Seizure is the main
      clinical presentation of CVST. The main radiologic manifestations are cerebral
      infarction and hemorrhage. Timely brain MRI and MRV are helpful in the early
      diagnosis and treatment of CVST.

PMID- 30293282
TI  - [Clinical and pathological features and mutational types of WT1 mutation
      associated nephropathy].
AB  - Objective: To explore the clinical and pathological features and mutational types
      and their relations with WT1 mutation-associated nephropathy (WT1MAN). Methods:
      The clinical and pathological data and the results of WT1 mutation analysis of
      the cases from Nanfang Hospital of Southern Medical University, Sun Yat-sen
      Memorial Hospital and The First Affiliated Hospital of Sun Yat-sen University
      whom we recruited recently and reported during the last ten years were analyzed.
      Results: Totally, 20 cases (6 males and 14 females), included 5 newly diagnosed
      cases, were recruited. (1) Ten children were diagnosed with Denys-Drash syndrome
      (DDS): The median onset age of proteinuria was 1 year and 7 months. Diffuse
      mesangial sclerosis (DMS) were revealed in 3 cases, minimal lesions (MCD) in 4
      cases, and focal segmental glomerulosclerosis (FSGS) in 1 case; renal pathology
      was not available in the other 2 cases. Glomerular basement membrane (GBM)
      thickening was observed in 2 cases. Calcineurin inhibitors (CNIs) were
      administered in 5 cases, complete remission of proteinuria was observed in 3
      cases, partial remission in the other 2 cases. Genetic analysis revealed that six
      cases had WT1 missense mutation, 3 had nonsense mutation, and 1 had frameshift
      mutation. (2) Two cases were diagnosed with Frasier syndrome (FS): proteinuria
      was observed at 1 year and 1 month of age and 1 year and 9 months of age,
      respectively. FSGS with GBM layering were observed in both cases. They progressed
      to ESRD at 1 year and 6 months of age and 6 years and 6 months of age,
      respectively. CNI was tried in 1 case with partial proteinuria remission. Both
      patients were detected to have WT1 splice mutation. (3) Isolated nephropathy (IN)
      was observed in 8 cases: three had splice mutation, 5 had missense mutation. Of
      the 3 patients with splice mutation, one was found to have nephropathy and renal
      failure at the age of 5 months. The other two cases (1 was FSGS and another MCD),
      both had GBM layering. CNIs were tried on both of them, one got partial remission
      with normal renal function at the age of fourteen years, the other one had no
      response and entered ESRD at the age of 6 years and 9 months. Of the 5 cases with
      missense mutation, 3 had DMS, 2 of them entered ESRD within 6 months of age,
      another case had DMS entered ESRD at 9 years of age. One case with FSGS, was
      treated with CNIs and got complete remission. Conclusions: Slow progression
      (7/10) nephropathy was observed in DDS patients. Missense mutation (11/20) was
      the most common type of WT1 variants, followed by splice mutation (5/20) in this
      group of patients. Early onset nephropathy (4/5), rapid progression (4/5) and GBM
      layering (4/4) wereobserved in patients with splice mutation. CNI was effective
      in reducing or even eliminating proteinuria in WT1 MAN patients (8/9).

PMID- 30293283
TI  - [No.145: fever, cough for 9 days, weakness, shortness of breath for 3 days].

PMID- 30293284
TI  - [Temporary neonatal cyanosis caused by heterozygous mutation of HBG2 gene].

PMID- 30293286
TI  - [Chronic granulomatous disease in aninfant with inflammatory bowel disease].

PMID- 30293285
TI  - [A novel compound heterozygous mutations in LAMC3 in a boy with infantile
      spasms].

PMID- 30293287
TI  - [Cytomegalovirus enteritis in an immunocompetent child].

PMID- 30293288
TI  - [Research progress in the risk factors of juvenile idiopathic arthritis
      associated uveitis and its severe visual outcome].

PMID- 30293290
TI  - [Influence factors of respiratory microbiota development in early infancy and its
      relationship with respiratory diseases].

PMID- 30293289
TI  - [Sleep problems in children with autism spectrum disorder].

PMID- 30293291
TI  - [Minutes of the National Neonatology Conference (2018)].

PMID- 30293292
TI  - [Expert consensus on the midterm pregnancy termination complicated with placenta
      previa status and increta after cesarean section].

PMID- 30293293
TI  - [Perinatal outcomes of thoraco-amniotic shunting for severe primary fetal
      hydrothorax].
AB  - Objective: To evaluate the safety and perinatal outcomes of thoracoamniotic
      shunting in the treatment of fetuses with severe primary hydrothorax. Methods: 22
      cases of suspected severe primary fetal hydrothorax which underwent thoraco
      amniotic shunting in Shanghai First Maternity and Infant Hospital, Fetal Medicine
      Unit and Prenatal Diagnosis Center from January 2012 to December 2017 were
      analyzed retrospectively. Hydrothorax associated with structural or chromosomal
      abnormalities, infections and immune fetal hydrops were excluded. Results:
      Totally, 28 shunts were placed in 22 fetuses. The median gestational age at TAS
      was 31.3 weeks. Preterm membrane rupture within 7 days after the procedure
      occurred in 9.1% (2/22) cases. Catheter displacement occurred in 18% (4/22)
      cases. The interval from shunting to delivery was 26.0 days. One fetus ended in
      induced abortion; 21 (95%, 21/22) babies were born alive, and their median
      gestational age at delivery was 34.4 weeks. 62% (13/21) newborns required
      ventilator supports; 4 neonatal deaths were attributed to pulmonary hypoplasia.
      The overall perinatal survival rate was 81% (17/21) . The perinatal survival rate
      with hydrops and without hydrops were 10/13 and 7/8 respectively. Conclusion:
      Thoraco-amniotic shunting is a safe procedure for intrauterine therapy and could
      improve the perinatal outcomes of severe primary fetal hydrothorax.

PMID- 30293294
TI  - [Relationship between thyrotropin and urine iodine in Han and Uygur nationalities
      pregnancy women in People's Hospital of Xinjiang Uygur Autonomous Region].
AB  - Objective: To investigate the relationship between thyrotropin (TSH) and urine
      iodine in pregnant women of Han and Uygur ethnic groups in People's Hospital of
      Xinjiang Uygur Autonomous Region. Methods: A total of 1 568 pregnant who
      completed screening of TSH and urine iodine in People's Hospital of Xinjiang
      Uygur Autonomous Region hospital from August 2014 to December 2017 were included
      in the study, 956 cases were Han and the other 612 were Uygur. Basic clinical
      data, serum TSH, thyroid peroxidase autoantibody (TPOAb) , and urine iodine
      levels were retrospectively analyzed. Results: (1) General results: The median
      urine iodine level was 162.6 MUg/L (53.4-539.3 MUg/L) , and the distribution of
      urine iodine classification was iodine deficiency 42.9% (672/1 568) , iodine
      appropriate 36.7% (576/1 568) , iodine slightly high 17.1% (268/1 568) and iodine
      excess 3.3% (52/1 568) respectively. (2) The median urine iodine levels of Han
      and Uygur pregnant women were 169.1 MUg/L (54.6-583.4 MUg/L) and 156.3 MUg/L
      (53.1-539.3 MUg/L) respectively, and the difference was statistically significant
      (P<0.05) .The distribution of urine iodine status in pregnancy between Han and
      Uygur was significantly different, which were 40.9% (391/956) vs. 45.9% (281/612)
      in iodine deficiency, 35.4% (338/956) vs. 38.9% (238/612) in iodine appropriate,
      20.2% (193/956) vs. 12.3% (75/612) in iodine slightly high and 3.6% (34/956) vs.
      2.9% (18/612) in iodine excess. (3) High serum TSH level proportion was
      significantly higher in Uygur ethnic group, early pregnancy, thyroid peroxidase
      antibody positive and anti-thyroglobulin antibody positive group when compared
      with Han, late pregnancy, thyroid peroxidase antibody negative and anti
      thyroglobulin antibody negative groups (all P<0.05) . There were no significant
      differences in different age groups and iodine nutrition groups (P>0.05) . (4)
      There was no correlation between urinary iodine and TSH levels in all pregnant
      women (P>0.05) , neither in Han or Uygur group. When further stratified by
      gestational age, age, and antibody level, there was a positive correlation
      between urine iodine and serum TSH level in Han pregnant women >30 years old
      (P<0.05) , and there was a negative correlation in the third trimester in Uygur
      (P<0.05) . When serum antibody level, gestational week and age were controlled.
      There was no correlation between urine iodine and serum TSH level in neither
      group. Conclusions: (1) In Han and Uygur pregnant women, the median urine iodine
      level and the distribution of urine iodine classification between two ethnic
      groups are significantly different. (2) The correlation between urine iodine and
      serum TSH is not identified in Han or Uygur pregnant women.

PMID- 30293295
TI  - [Clinical multicenter study of carboprost methylate suppository for cervical
      ripening prior to diagnostic hysteroscopy].
AB  - Objective: To evaluate the effectiveness of carboprost methylate suppository for
      cervical ripening before diagnostic hysteroscopy in premenopausal women. Methods:
      From July 2014 to July 2015, 1 614 women who were undergone diagnostic
      hysteroscopy in 12 hospitals were randomly assigned into study group (n=1 209)
      and control group (n=405) . The cases in study group were given 1 mg carboprost
      methylate suppository in vagina before hysteroscopy, the cases in control group
      were given 1 mg placebo. The extent of cervical ripening, the time of dilated
      cervix, pain scoring, incidence of drug side reactions after 24, 48, 72 hours,
      satisfaction degree of operators and patients, the time of hysteroscopy,
      incidence of complications between the two groups were observed and compared.
      Results: (1) Mean cervical widths in the study and control groups were 6.11+/
      1.11 and 5.95+/-1.11, and showed a significant difference (P=0.034) ; the
      percentage of women requiring cervical dilatation in study group was lower than
      the percentage in control group significantly [28.3% (342/1 209) versus 34.6%
      (140/405) , P=0.020]. (2) The time of dilated cervix in study group was shorter
      than the time in control group significantly [ (34+/-25) versus (52+/-49) s,
      P=0.028] for the patients whose mean cervical widths<=4. (3) There was no
      significant difference in pain scores between the two groups (P>0.05) . (4) The
      incidence of side reactions 24, 48, 72 hours after operation were no significant
      difference between the two groups (P>0.05) . (5) The satisfaction degree of
      operators and patients, the time of hysteroscopy, incidence of complications
      between the two groups were no singnifcant difference between the two groups (all
      P>0.05) . Conclusion: Application of carboprost methylate suppository by vagina
      before hysteroscopy is an effective and safe method of cervical ripening.

PMID- 30293296
TI  - [Method selection and perioperative management of termination of pregnancy during
      the first and second trimester of pregnancy with severe cardiovascular disease].
AB  - Objective: To summarize and analyze the methods of termination of pregnancy in
      the first and second trimester of pregnancy with severe cardiovascular disease.
      Methods: A retrospective analysis of 27 cases of termination of pregnancy in the
      first and second trimester of pregnancy in Beijing Anzhen Hospital from January
      1, 2016 to December 30, 2017. All of these pregnant women were pregnancy
      complicated with severe cardiovascular disease in grade V pregnancy risk.
      Results: (1) The age of 27 pregnant women was 22-40 years, gestational age was 6
      27 weeks; cardiac function grade before induced labor was: 5 cases of grade II,
      15 cases of grade III, 7 cases of grade IV. The cardiovascular diseases included
      ventricular septal defect in 9 cases, simple atrial septal defect in 3 cases,
      patent ductus arteriosus in 2 cases, tetralogy of Fallot in 2 cases, rheumatic
      valvular disease in 1 case,arrhythmia-paroxysmal atrial velocity in 2 cases,
      cardiomyopathy in 2 cases, hypertensive cardiopathy in 2 cases, primary pulmonary
      hypertension in 1 case, tissue disease complicated with pulmonary hypertension 1
      case, hyperthyroid heart disease in 1 case, coronary heart disease in 1 case.
      Among them, 21 cases were complicated with pulmonary hypertension, and 5 cases
      with Eisenmenger syndrome. (2) Methods of termination of pregnancy: in 27 cases,
      eight cases of vacuum curettage, and 2 cases of forceps curettage under general
      anesthesia without intubation; rivanol intraamniotic induction of labor in 1
      case; and hysterotomy delivery in 16 cases (11 cases were treated with continuous
      epidural anesthesia, 1 case was treated with combined spinal and epidural
      anesthesia, 4 cases were treated with spinal anesthesia) . (3) After termination
      of pregnancy, one patient with severe primary pulmonary hypertension at 19 weeks
      of gestation died on the 1st day postoperative. No significant changes in cardiac
      function were observed in other patients before and after termination of
      pregnancy, and all of them survived. Conclusions: In patients with severe
      cardiovascular disease, termination of pregnancy after pregnancy may result in
      maternal death even at the second trimester of pregnancy.It is strongly
      recommended that such patients undergo pre-pregnancy assessment and fertility
      counseling.If visiting doctor after pregnancy, we should organize a
      multidisciplinary consultation as soon as possible to assess the risk of
      continuing pregnancy and give medical advice. If the risk of pregnancy is high,
      we should terminate the pregnancy as early as possible, after making a suitable
      treatment plan. During termination of pregnancy, temporary or permanent
      contraception may be taken if the condition permits.

PMID- 30293297
TI  - [Analysis of the missed diagnosis of invasive carcinoma under the microscope in
      HSIL diagnosed by colposcopy-guided biopsy and related influencing factors].
AB  - Objective: To observe the missed diagnosis of invasive carcinoma under the
      microscope (ICUM) in high grade squamous intraepithelial neoplasia (HSIL) , and
      analyze associated factors influencing missed ICUM. Methods: A retrospective
      study was performed on patients diagnosed with HSIL by colposcopy-guided biopsy
      and treated with loop electrosurgical excision procedure (LEEP) at the First
      Affiliated Hospital of Nanjing Medical University, from December 2014 to December
      2016. They were non-pregnant, <=50 years old and the cervical volume without
      obvious enlargement and exogenous surface without and ulcerative lesions. A total
      of 283 cases with early cervical cytology results, never received cervical
      traumatic treatment or cervical biopsy in another hospital before, and their
      colposcopic images were clear enough to reevaluate. The ultimate pathological
      diagnosis was based on the higher-level pathological diagnosis between the
      results of cervical biopsy and LEEP to evaluate ICUM missed in HSIL and the risk
      factors. Results: (1) Among the 283 cases with HSIL diagnosed by colposcopy
      directed biopsy, 44 cases (15.5%, 44/283) were missed diagnosis of ICUM, which
      consisted of 29 cases I a1, 4 cases I a2 and 11 cases I b1 in the ultimate
      pathology. (2) Analysis of associated factors for missed ICUM: univariate
      analysis showed that, as the age increased, the risk of missed ICUM also
      increased (the rates of missed diagnosis for <30, 30-39, 40-50 years were 7.7%,
      11.5%, 22.0%, respectively; chi(2)=6.254, P=0.012 by trend test) . The more the
      number of high-grade features, the higher risks (the rates of missed diagnosis
      for 1, 2, 3, 4 high-grade features were 10.2%, 17.6%, 23.8%, 30.8%, respectively;
      chi(2)=7.686, P=0.006 by trend test) . The locations of HSIL were only
      endocervical, only ectocervical and mixed, the risk increased by this sequence
      (2.8%, 5.1%, 28.7%; chi(2)=26.193, P<0.01 by trend test) . The rate of missed
      diagnosis for not completely visible squamocolumnar junction (SCJ) was higher
      than that of the completely visible one (22.3% vs 2.1%; chi(2)=19.680, P<0.01) .
      The rate of missed diagnosis was higher for existing atypical vessels than those
      without (60.7% vs 10.6%; chi(2)=48.279, P<0.01) . The rate of missed diagnosis
      for visible lesion size >=40 mm(2) was higher than that of <40 mm(2) (27.3% vs
      4.2%; chi(2)=28.921, P<0.01) . The rate of missed diagnosis for the proportion of
      visible lesion size in ectocervical size >=0.75 was higher than that of <0.75
      (83.3% vs 14.1%; P<0.01) . The rate of missed diagnosis for the maximum linear
      length of visible lesion >=10 mm was higher than that of <10 mm (46.9% vs 9.0%;
      chi(2)=44.473, P<0.01) . But the different severity of cervical cytology before
      colposcopy was not associated with missed ICUM (P>0.05) . Multivariable analysis
      found that visibility of SCJ, atypical vessels, visible lesion size and maximum
      linear length of visible lesion were associated with missed diagnosis of ICUM
      (all P<0.05) . Conclusions: The diagnostic value of HSIL by colposcopy is
      limited. Meanwhile, for the patients who are <=50 years old with HSIL diagnosed
      by cervical biopsy, invisibility of SCJ, atypical vessels, visible lesion size
      and maximum linear length of visible lesion evaluated by colposcopy are the
      independent risk factors of missed ICUM. Thereby, it is necessary to take active
      intervention for HSIL with these risk factors.

PMID- 30293298
TI  - [Clinical management of 110 cases of polypropylene mesh and sling exposure after
      reconstructive pelvic floor surgery].
AB  - Objective: To explore the clinical management and outcomes of polypropylene mesh
      and sling exposure after reconstructive pelvic surgery (RPS) . Methods: A total
      of 110 cases of mesh and sling exposure after RPS were analyzed, who admitted
      between Jan. 2002 and Oct. 2017 in First Affiliated Hospital of PLA General
      Hospital, in which 3 cases were referred from other hospitals. Mesh and sling
      exposures were identified in the outpatient clinic and categorized and managed
      according to International Continence Society and International Urogynecology
      Association (ICS-IUGA) classification about category, time and site (CTS) of mesh
      complication. Outpatient management included observation, topical estrogen use
      and mesh removal. Management in hospital included surgical removal of exposed
      mesh and repair of the resulting defects under the anesthesia. Seventy-four cases
      were managed in the outpatient setting, and 36 cases required inpatient
      management. Follow-up was consecutively performed from 1 month to 10 years.
      Objective outcome included the surgeon's assessment of the healing state of the
      vaginal mucosa. Subjective outcome was evaluated with patient global impression
      of improvement questionnaire (PGI-I) . Results: One hundred and ten patients with
      mesh exposure were classified according to the different RPS underwent. There
      were 95 cases from transvaginal mesh surgery, 5 cases from anti-stress urinary
      incontinence sling surgery, and 10 cases from sacrocolpopxy. The outpatient group
      healed at an average of (3.0+/-1.8) months. Of the 36 patients who required
      inpatient management, 21 cases healed completely at an average of 7 days after
      one surgery. The remaining 8 cases required either two or three times surgeries
      or conservative management. In the outpatient group, the PGI-I scale very much
      better was found in 65 cases (87.8%) and much better in 9 cases (12.2%) . In the
      inpatient surgery group, the scale was very much better in 30 cases (83.3%) , and
      much better in 6 cases (16.7%) . Conclusions: Among patients with mesh exposure
      after mesh-augmented RPS, 2/3 of patients with a CTS classification 1-3 could be
      managed in the office, and remaining 1/3 with CTS classification 4-6 need
      operation under anesthesia in hospital. If the mesh and sling exposure could be
      scientifically classified, according to the size, site and accompany symptoms, as
      well as pain, most of the mesh complications after explosure could be resolved.
      Using the pelvic floor repair and polypropylene mesh sling, the majority of the
      patients could get a better outcome, without affecting the effect of the original
      operation.

PMID- 30293299
TI  - [Rupture of uterus and penetrated small intestine caused by placenta percreta: a
      case report].

PMID- 30293300
TI  - [Spatial epidemiology plays an important role in control and prevention of
      diseases].
AB  - Spatial epidemiology is a new branch of epidemiology that aims to map the spatial
      distribution and characteristics as well as to explore the associated influencing
      factors of diseases by using the geographic information system and other spatial
      technologies. In recent years, with the rapid development of information-related
      modern technology, improvement of accessibility on health - related services,
      natural environment, social and economic big data etc., spatial epidemiology has
      made considerable progress in both theory and practice and played more important
      roles in the public health area of China.

PMID- 30293301
TI  - [Epidemiological features of hepatitis C and its related influencing factors in
      Shandong province, 2007-2016].
AB  - Objective: To analyze the epidemiological characteristics, dynamic trend of
      development and related influencing factors of hepatitis C in Shandong, China,
      2007-2016, also to provide epidemiological evidence for prevention and control of
      HCV. Methods: National surveillance data of hepatitis C from 2007 to 2016 in
      Shandong was used, with distribution and clustering map of hepatitis C drawn at
      the county level. Panel Poisson regression was used to explore the influencing
      factors of hepatitis C at the city level. Results: The incidence of hepatitis C
      in Shandong increased from 1.49/100 000 in 2007 to 4.72/100 000 in 2016, with the
      high incidence mainly clustered in the urban regions in Jinan, Zibo, Weihai et
      al. and surrounding vicinities. Majority of the cases were young adults, with
      53.16% (14 711/27 671) of them being farmers. Results from the Multiple panel
      Poisson regression analysis indicated that factors as: population density
      (aIRR=1.07, 95%CI: 1.05-1.10), number of hospital per hundred thousand people
      shared (aIRR=1.16, 95%CI: 1.08-1.24), expenditure of medical fee in rural
      (aIRR=1.21, 95%CI: 1.08-1.37) and the proportion of the tertiary industry
      (aIRR=1.08, 95%CI: 1.07-1.09) were all correlated to the incidence of hepatitis
      C. Conclusions: The incidence of hepatitis C had been increasing rapidly in
      recent years, in Shandong. Prevention and control of HCV should focus on high
      risk population. In addition, rural, especially in areas with lower economics
      provision should be under more attentions, so as to find more concealed cases for
      early treatment.

PMID- 30293302
TI  - [Analysis on the spatial-temporal characteristics of hand-foot-mouth disease in
      Shaanxi province, 2009-2013].
AB  - Objective: To study the spatial-temporal dynamical features of hand-foot-mouth
      disease (HFMD) in Shaanxi Province, so as to provide evidence for the development
      of relative prevention and control programs on HFMD. Methods: Surveillance data
      of HFMD was collected from the China Information System for Diseases Control and
      Prevention from 2009 to 2013. Related data on population and gross domestic
      product (GDP) was obtained from Shaanxi Statistical Yearbook. Statistical tools
      as R3.4.1, ArcGIS 10.2 and SaTScan 9.2 software were used to describe the spatial
      temporal distribution of the disease. Power-law method on spatial-temporal
      multicomponent model was used to analyze the spatial-temporal evolution of the
      HFMD epidemics in Shaanxi Province. Results: A total of 229 904 cases of HFMD
      were reported in Shaanxi Province from 2009 to 2013, with an average annual
      incidence as 122.50 per 100 000. Obvious seasonal characteristics were noticed,
      with 71.71% of the total cases identified between April and July. Counties with
      high incidence were mainly distributed in the mid-and east parts of Guanzhong
      area. Through temporal and spatial scan statistics, we identified that ClassI
      clustering area was fixed to the central and southeast regions of Shaanxi
      province which were around Xi'an City between 2009 and 2013, with the relative
      risk (RR) as 2.24, ranging from 2.18 to 3.08. Results from Power-law analysis
      showed that the continuous follow-up impact from the previous HFMD epidemics
      appeared strong in Tongguan, Pucheng districts of Weinan City and Weiyang
      district of Xi'an, with autoregressive components as 1.14, 0.97 and 0.89,
      respectively. The risk of HFMD seemed high in Huayin city, Changan and Yanta
      districts and with the endemic components as 5.08, 4.12 and 4.08, respectively.
      Impact of the epidemics on nearby districts was largely seen in Lianhu district
      of Xi'an, Wugong district of Xianyang and Gaoling district of Xi'an with epidemic
      components as 2.12, 2.08 and 1.77, respectively. The etiological constituents of
      HFMD were mainly Enterovirus 71 between 2009 and 2012, while HFMD was mainly
      caused by other entero-viruses, in 2013. Conclusion: Significant spatial-temporal
      heterogeneity of HFMD was seen in Shaanxi province, which called for specific
      strategies to be developed in the highly endemic areas.

PMID- 30293303
TI  - [Epidemiological characteristics and environmental risk factors of hemorrhagic
      fever with renal syndrome in Wei River basin, China, 2005-2015].
AB  - Objective: To understand the epidemiological characteristics of hemorrhagic fever
      with renal syndrome (HFRS) in Wei River Basin from 2005 to 2015, and analyze the
      environmental factors that cause the differences of spatial distribution.
      Methods: HFRS reported cases in Wei River Basin from 2005 to 2015 were collected
      form "National Disease Reporting Information System" , and the epidemiological
      features of HFRS were analyzed. Boosted regression trees (BRT) model was applied
      to evaluate the environment factors on the geographical distribution of HFRS in
      Wei River basin at 5 km*5 km gird scale. Results: The number of HFRS cases was 18
      629, and the average annual incidence from 2005-2015 in Wei River basin was
      7.24/100 000. The highest morbidity was 15.18/100 000 in 2012. The middle and
      lower reaches of Wei River basin had high incidence of HFRS, such as Xi'an,
      Weinan city. Patients' age was mainly between 16 to 60, and the largest morbidity
      occured in people over 60 years old. Boosted regression trees modle identified
      building land, farmland coverage percentage and altitude had higher contribution
      to the distribution of HFRS. Conclusions: The epidemiological characteristics of
      HFRS changed significantly. Patients older than 60 years old were having the
      highest incidence rates. Environmental factors such as buildup land, farmland and
      altitude played important roles in the geographical distribution of HFRS in the
      Wei River basin.

PMID- 30293304
TI  - [Characteristics on spatial and temporal distribution as well as the driving
      effect of meteorological factors on brucellosis in Datong city, Shanxi province,
      2005-2015].
AB  - Objective: To explore the spatio-temporal epidemic trends and related driving
      effects of meteorological factors on brucellosis in Datong city, Shanxi province,
      from 2005 to 2015. Methods: We collected the surveillance data on brucellosis and
      related meteorological data in Datong city from 2005 to 2015, to describe the
      epidemic characteristics of the disease. Quasi-Poisson distribution lag non-liner
      model (DLNM) was built to explore the driving effect of monthly meteorological
      data on the disease. Results: From 2005 to 2015, Datong city reported a total of
      17 311 cases of brucellosis including one death, with the annual average
      incidence as 47.43 per 100 000 persons. A rising trend was seen during the study
      period. The monthly incidence of Brucellosis presented an obvious curve with a
      major peak from March to June, accounted for 48.40% of the total cases. The high
      incidence areas in the city gradually expanded from the northeast and southeast
      to the western areas. Results from the DLNM studies suggested that seasonality of
      brucellosis in Datong was significantly affected by metrological factors such as
      evaporation, rainfall and temperature. The peak of delayed effect appeared the
      highest when the monthly cumulative evaporation capacity was 140-260 mm and the
      monthly cumulative rainfall was 20-60 mm with lag less than 1 month or the
      monthly temperature was -13 C with lag of 4-5 months. Conclusions: The incidence
      of human brucellosis in Datong city increased significantly from 2005 to 2015.
      Meteorological factors such as evaporation, rainfall, temperature all showed
      significant driving effects on the disease.

PMID- 30293306
TI  - [Epidemiologic survey on the prevalence and distribution of infants' common
      gastrointestinal symptoms in 7 cities in China: a population-based study].
AB  - Objective: Regurgitation, infantile colic, and functional constipation are common
      gastrointestinal symptoms in childhood, the aim of this study was to explore the
      prevalence and distribution of these symptoms in China. Methods: A screening
      program in infants aged 0 to 3 years selected through stratified cluster random
      sampling was carried out in 7 cities in China. Questionnaires were filled, and
      then diagnosis were made according to Rome IV criteria. Areas, (urban-rural), age
      and gender distribution of prevalence of childhood common gastrointestinal
      symptoms were analyzed. Results: Totally, 20 932 effective questionnaires were
      returned. The total number of infants aged 0 to 1 years was 10 193. Regurgitation
      was diagnosed in 1 960 infants, with the prevalence of 19.2%, among infants aged
      0 to 3 months that had highest prevalence (29.8%). The prevalence decreased with
      age, and differences among different age groups showed significant. For infantile
      colic, 4 470 infants aged 0 to 5 months were analyzed and the prevalence of
      infantile colic was 7.3%. The prevalence of infantile colic was the highest in
      infants aged 1 to 2 months (10.0%). Age specific difference was significant. Of
      all the infants, functional constipation was diagnosed in 1 755 infants with the
      prevalence of 8.4%, and the lowest prevalence was found in infants aged 0 to 3
      months (6.2%), and the highest prevalence was in infants aged 30 to 36 months
      (10.0%). The differences in different age group were significant. Conclusion:
      Symptoms of regurgitation, infantile colic, and functional constipation are
      common in infants in China, with age specific difference in prevalence of the
      symptoms.

PMID- 30293305
TI  - [Association between central obesity and risk for heart disease in adults in
      China: a prospective study].
AB  - Objective: To understand the association between central obesity, assessed by
      waist circumference, and the risks for ischemic heart disease (IHD), major
      coronary event (MCE), and IHD death. Methods: After excluding participants with
      heart disease, stroke, cancer, COPD, and diabetes at baseline survey, we included
      a total of 428 595 participants from the China Kadoorie Biobank for the analysis.
      The baseline survey was conducted from June 2004 to July 2008. We used Cox
      proportional hazards model to estimate the hazard ratio (HR) and 95%CI. Results:
      During an average 9.1 years of follow-up (3 803 637 person-years), we documented
      26 900 incident cases of IHD, 4 320 cases of MCE, and 2 787 of deaths from IHD.
      After adjustment for possible confounders and BMI, central obesity was found to
      be associated with increased risks for IHD, MCE, and IHD death. The adjusted HRs
      (for the participants who had waist circumference of 85.0-89.9 cm in men and 80.0
      84.9 cm in women were 1.13 (95%CI: 1.09-1.17) for IHD, 1.15 (95%CI: 1.05-1.26)
      for MCE and 1.11 (95%CI: 0.98-1.24) for IHD death. The respective HRs for those
      central obese participants (men >=90.0 cm, women >=85.0 cm) were 1.29 (95%CI:
      1.24-1.34), 1.30 (95%CI: 1.17-1.44) and 1.32 (95%CI: 1.16-1.51). Further
      stratification analysis according to BMI showed that the risks for incident IHD,
      MCE, and IHD death increased along with the increase of waist circumference even
      in the participants with normal weight. Conclusion: This large-scale prospective
      study revealed that central obesity was an independent risk factor for IHD in
      adults in China, and the risk of IHD would increase with the increase of waist
      circumference.

PMID- 30293308
TI  - [One year after the implementation of 2015 Tobacco Control Regulation on persons
      aged 15 years and over tobacco use in Beijing].
AB  - Objective: To understand the current status of smoking and smoking cessation in
      persons aged 15 years and over in Beijing and evaluate the effect of 2015 Beijing
      Tobacco Control Regulation. Methods: In 2014 and 2016, based on the principles
      and methodology of the Global Adult Tobacco Survey. A total of 50 communities or
      townships were selected from 324 communities or townships in Beijing through
      multistage cluster sampling, and 2 community (village) committees from each
      community or township were selected with the method of probability proportional
      to size (PPS). A total of 100 surveillance sites were set, and 100 households
      were selected from each surveillance site by using simple random sampling. Data
      were collected through face-to-face interview from the eligible family members
      aged 15 years and over with the assistance of a tablet computer. Statistical
      analyses were conducted by using complex sampling analyses module of SPSS 20.0,
      with weights as a combination of sampling weights, non-response weights and post-
      stratification weights, for the calculation of current smoking prevalence, daily
      smoking prevalence, smoking cessation rate, etc. Results: A total of 8 484 and 9
      372 valid questionnaires were obtained, respectively, in 2014 and 2016, with the
      response rate of 86.5% and 96.5%. The current smoking prevalence in persons aged
      15 years and over was 23.4% in 2014, and 22.3% in 2016. According to the 6(th)
      national census data, the current smoking population decreased by 199 000 in
      Beijing. The proportion of daily smokers declined from 20.7% in 2014 to 19.2% in
      2016. The daily number of cigarettes consumed by current smokers increased from
      14.6 in 2014 to 15.4 in 2016. The smoking cessation rate was 14.9% in 2014 and
      16.8% in 2016. The proportion of current smokers who had at least one smoking
      cessation attempt in the past 12 months increased from 22.3% in 2014 to 23.2% in
      2016, and the proportion of current smokers who planned to quit smoking increased
      from 11.6% to 15.5%. Among the current smokers who had visited doctors in the
      past 12 months, the proportion of those having smoking cessation advice was 58.9%
      in 2014 and 59.2% in 2016. In 2016, among the current smokers who had attempted
      to quit in the past 12 months, 36.8% were aware of the smoking cessation clinics,
      and 29.5%were aware of the quitline. Among those who were aware, only 7.7% had
      actually visited the cessation clinics, and 5.5% had used the quitline.
      Conclusions: After the implementation of 2015 Beijing Tobacco Control Regulation
      for 1 year, the current smoking prevalence in persons aged 15 years and over
      showed decreasing. It is necessary to further prompt the expansion of smoking
      cessation service to cover more current smokers.

PMID- 30293309
TI  - [Subjective well-being feelings and related factors in people aged 50 years or
      older in Shanghai: Based on Day Reconstruction Method].
AB  - Objective: To evaluate the subjective well-being feelings of people aged >=50
      years in Shanghai by using the Day Reconstruction Method (DRM) and explore the
      related factors. Methods: A cross-sectional survey was conducted from October
      2009 to June 2010 among people aged >=50 years selected through multistage random
      cluster sampling in Shanghai. DRM was used to assess participants' subjective
      well-being by net effect and U-index. Univariate and multivariate linear
      regression models were used to explore the related factors. Results: A total of 8
      075 participants were included, with average age of 63.1 years. The mean net
      effect value was 1.24 (95%CI:1.15-1.33), and the mean U-index was 1.55%
      (95%CI:1.10%-1.99%). After adjusted for demographic factors, univariate liner
      regression model indicated that age, education level, marital status, family
      wealth, residence, self-rated health status, WHODAS score and prevalence of
      chronic disease were associated with subjective well-being, and multivariate
      liner regression model indicated that higher WHODAS score was associated with
      lower net effect value (P<0.05). Conclusion: The subjective well-being feelings
      of people aged >=50 years in Shanghai might be associated with age, education
      level, marital status, family wealth, residence, self-rated health status and
      WHODAS score. Enhanced social support and appropriate social security system
      might facilitate the improvement of the subjective well-being of the elderly.

PMID- 30293307
TI  - [Prospective association between childhood abuse experiences and depressive
      symptoms in adolescence].
AB  - Objective: To evaluate the prospective association between childhood abuse
      experiences and depressive symptoms in adolescence. Methods: Students in grade 3
      and 4 from three primary schools were selected, with informed consent, through
      convenience cluster sampling in Bengbu, Anhui province in May 2013. The students'
      body height, weight were assessed. Childhood abuse experiences including
      emotional, physical or sexual abuses, as well as depressive symptoms were
      reported by children themselves. Data on parental educational background and
      household economic status were collected through parent questionnaire. A follow
      up was conducted 4 years later after baseline survey. Depressive symptoms were
      evaluated by using Children's Depression Inventory at baseline survey, and by
      using Mood and Feeling Questionnaire at follow-up. Logistic regression model was
      used to analyze the relationship between childhood abuse experiences and
      depressive symptoms in adolescence. Results: A total of 1 172 students were
      included in baseline survey, and a follow-up was conducted for 87.1% of them (n=1
      021). Among 1 126 students with complete information on childhood abuse
      experiences at baseline survey, the reported rates of physical, emotional and
      sexual abuses were 12.8% (144/1 126), 11.1% (125/1 126) and 10.9% (123/1 126),
      respectively. The prevalence of depressive symptoms at baseline survey and follow
      up was 7.0% (82/1 172) and 12.3% (126/1 021), respectively. After adjusted for
      baseline depressive symptoms, age at follow-up, sex, the only-child in family,
      household economic status, divorce of parents and BMI, childhood emotional and
      physical abuse experiences were significant risk factors for depressive symptoms
      in mid-adolescence, with the ORs were 1.86 (95%CI: 1.03-3.36, P=0.039) and 2.37
      (95%CI: 1.39-4.03, P=0.001), respectively. Conclusion: Childhood physical and
      emotional abuse might increase the risk of depressive symptoms in adolescence.

PMID- 30293310
TI  - [Association between tea drinking and stroke in adults in Zhejiang province: a
      prospective study].
AB  - Objective: To prospectively explore the association between tea drinking and
      incidence of stroke of adults of Zhejiang province. Methods: After excluding
      participants with heart disease, stroke, cancer and diabetes at baseline study,
      53 916 participants aged 30-79 years in the China Kadoorie Biobank (CKB) study
      from Tongxiang were included for final analysis. Cox regression model was used to
      estimate the hazard ratio (HR) for the association of tea drinking with incident
      stroke. Results: The main type of drinking tea was black tea (79.78%), followed
      by green tea (20.08%). Of the 53 916 participants, the proportion of participants
      who drank tea at least once per week was 31.27%. The corresponding proportions
      for men and women were 60.24% and 10.30%, respectively. Among 391 512 person
      years of the follow-up program (median 7.26 years), a total of 1 487 men and 1
      769 women were diagnosed with stroke. After adjusting for socio-demographic
      status, lifestyle, BMI, waist circumference, and systolic blood pressure, HR for
      incident stroke decreased with the increase of daily average tea consumption
      amount (P=0.000 6). Compared with participants who did not drink tea weekly, the
      HRs for incident stroke in those consuming tea 0.1-, 3.0- and >=5.0 g/d were 0.93
      (95%CI: 0.85-1.00), 0.88 (95%CI: 0.77-0.99) and 0.79 (95%CI: 0.69-0.89),
      respectively. The HRs for incident stroke in smokers and non-smokers who consumed
      tea >=5.0 g/d were 0.71 (95%CI: 0.59-0.86) and 0.97 (95%CI: 0.77-1.21),
      respectively, compared with current smokers and non-smokers who did not drink tea
      weekly (P=0.040 0). The corresponding HRs for alcohol drinkers and non-drinkers
      were 0.96 (95%CI: 0.76-1.22) and 0.70 (95%CI: 0.58-0.84), respectively (P=0.040
      0). The corresponding HRs for central obese persons and non-central obese persons
      were 0.60 (95%CI: 0.44-0.81) and 0.86 (95%CI: 0.73-1.01), respectively (P=0.040
      0). Conclusion: Tea drinking had an effect on reducing the possibility of
      incident stroke, especially among those who were current smokers, non-alcohol
      drinkers and central obese.

PMID- 30293311
TI  - [Prevalence of musculoskeletal disorders and related factors in female greenhouse
      workers in Shandong province].
AB  - Objective: To study the prevalence of musculoskeletal disorders (MSDs) and
      related factors in female greenhouse workers. Method: A questionnaire survey was
      conducted among 851 female greenhouse workers in Shandong province in 2015.
      Results: The incidence of MSDs among the female greenhouse workers was 82.79%.
      For the MSDs in female greenhouse workers, the top four affected body sites were
      low back (65.82%), knees (49.10%), neck (25.75%) and shoulder (23.47%).
      Multivariate logistic regression analysis showed that age >=50 years (OR=2.098,
      95%CI: 1.353-3.252), working years >=20 (OR=1.703, 95%CI: 1.116-2.599),
      repetitive work (OR=1.903, 95%CI: 1.183-3.061), standing for prolonged time
      (OR=2.902, 95%CI: 1.183-7.120) and frequent slightly bending down (OR=2.979,
      95%CI: 1.823-4.867) were the main risk factors for MSDs in female greenhouse
      workers. Aiding tools was the protective factor (OR=0.400, 95%CI:0.229-0.697).
      Conclusions: The findings showed a relatively higher prevalence of MSDs in female
      greenhouse workers. It is necessary to take appropriate measures to prevent and
      control the incidence of MSDs in female greenhouse workers.

PMID- 30293312
TI  - [Epidemiological characteristics of outbreaks of norovirus-GII.2, GII.17 and
      GII.4/Sydney in Guangdong province, 2013-2017].
AB  - Objective: To understand the epidemiologic characteristics of outbreaks, caused
      by norovirus-GII.2,GII.17 and GII.4/Sydney in Guangdong Province from 2013 to
      2017 and to provide scientific evidence for epidemic prevention and control.
      Methods: Incidence data of norovirus outbreaks in Guangdong from January 1(st)
      2013 to November 30(th) 2017 were collected from Public Health Emergency
      Management Information System. RT-PCR was performed for every case of each
      outbreak to detect norovirus nucleic acid and gene sequencing was conducted to
      identify the genotype of norovirus. Characteristics of norovirus GII.2, GII.17
      and GII.4/Sydney outbreaks were analyzed. Directly standardized method was used
      to calculate the proportion of symtoms as diarrhea and vomitting. Results: From
      January 1(st) 2013 to November 30(th) 2017, a total of 167 norovirus outbreaks
      were reported in Guangdong, and 115 outbreaks were caused by norovirus GII.2,
      GII.17 and GII.4/Sydney respectively. The outbreaks caused by norovirus GII.2
      accounted for 39.68% (25/63) in primary schools, 28.57% (18/63) in child care
      settings, 25.40% (16/63) in middle schools and 6.35% (4/63) in universities.
      Outbreaks caused by norovirus GII.17 accounted for 41.03% (16/39) in middle
      schools, 20.51% (8/39) at workplaces, 15.38% (6/39) in primary schools, 12.82%
      (5/39) in universities, 5.13% (2/39) in communities and child care settings
      respectively. The outbreaks caused by norovirus GII.4/Sydney accounted for 53.85%
      (7/13) in universities, 15.38% (2/13) in child care settings and at workplaces
      respectively, 7.69%(1/13) in primary schools and middle schools respectively. The
      outbreaks caused by norovirus GII.2 had 77.78% (49/63) of contact transmission,
      17.46% (11/63) of food-borne transmission. The outbreaks caused by norovirus
      GII.17 showed 53.85% (21/39) of food-borne transmission, 15.38% (6/39) of
      contract transmission, 12.82% (5/39) of water-borne transmission. The outbreaks
      caused by norovirus GII.4/Sydney had 53.85% (7/13) of food-borne transmission,
      38.46% (5/13) of the contact transmission. In terms of the clinical
      manifestations, the standardized proportion of vomit was 73.76% and the
      proportion of diarrhea was 42.85% in cases infected with norovirus GII.2, the
      proportion of standardized of vomit was 76.37% and the proportion of diarrhea was
      51.40% in cases infected with norovirus GII.17, with the standardized proportion
      of vomit was 54.10% and the proportion of diarrhea was 55.95% in cases infected
      with norovirus GII.4/Sydney. Conclusions: The outbreaks caused by norovirus GII.2
      through contact transmission mainly occurred in primary schools, child care
      settings and middle schools. The outbreaks caused by norovirus GII.17 through
      food-borne transmission mainly occurred in middle schools and at workplaces. The
      outbreaks caused by norovirus GII.4/Sydney food-borne transmission and contact
      mainly occurred in universities.

PMID- 30293313
TI  - [Effect of baseline CD(4)(+) T cell count on drop-out of antiretroviral therapy
      in HIV infected persons in Guangxi Zhuang Autonomous Region, 2008-2015].
AB  - Objective: To investigate the effect of baseline CD(4)(+) T cell count (CD(4)) on
      drop-out of antiretroviral therapy (ART) in HIV infected persons. Methods:
      Retrospective cohort was conducted in this study. HIV infected persons aged>=18
      years and receiving free ART for the first time in Guangxi Zhuang Autonomous
      Region (Guangxi) from 2008 to 2015 were selected from the antiretroviral
      treatment database of National Comprehensive HIV/AIDS Information System, with
      follow-up conducted till May 30, 2016. Cause-specific Cox proportional hazard
      models were used to evaluate effect of different CD(4) on the drop-out of ART in
      the HIV infected persons. Results: A total of 58 502 eligible study participants
      were included in this retrospective cohort study. The average drop-out ratio was
      4.8/100 person-years. After controlling the following baseline covariates: age,
      sex, marital status, route of HIV infection, WHO clinical stage before ART,
      initial/current ART regiment, ART regiment adjustment, and year of initiating ART
      for potential confounding, the adjusted HR of drop-out for HIV infected persons
      with 200- cells/MUl, 351-cells/MUl and >=500 cells/MUl were 1.110 (95%CI: 1.053
      1.171, P<0.001), 1.391 (95%CI: 1.278-1.514, P<0.001) and 1.695 (95%CI: 1.497
      1.918, P<0.001), respectively, in risk for drop-out compared with those with
      baseline CD(4)<200 cells/MUl. Among the HIV infected persons, 56.0% (1 601/2 861)
      of drug withdrawal was due to poor compliance with medication. Conclusions: With
      the increase of baseline CD(4) when initiating ART, the risk for the drop-out in
      HIV infected persons increased significantly. To further reduce the drop-out of
      ART, it is important to take CD(4) into account in initiating ART and to
      strengthen the health education on treatment compliancy and training for
      healthcare providers.

PMID- 30293315
TI  - [Evaluation on follow-up intervention program in men who have sex with men in
      Tianjin].
AB  - Objective: To evaluate the behavior intervention program on men who have sex with
      men (MSM) in Tianjin. Methods: From April 2013 to September 2017, MSM were
      enrolled from MSM gathering places and through mobile internet to establish an
      open prospective cohort. Interventions were conducted in every follow-up meeting,
      while the changes of behaviors and HIV infection and syphilis incidences in the
      MSM before and after intervention were compared. Results: A total of 1 822 MSM
      were interviewed at baseline survey, with 1 007 eligible MSM were enrolled in the
      cohort. A total of 39 new cases of HIV infection were reported, and the
      cumulative observation time on cohort follow-up was 2 216.96 person-year, with
      the HIV incidence rate as 1.76 per 100 person-years. Among them, 934 MSM were
      sero-negative for syphilis in baseline survey. A total of 100 new cases of
      syphilis were reported, and the cumulative observation time of cohort follow-up
      was 1 959.94 person-year, the syphilis incidence rate was 5.10 per 100 person
      years. With health education and intervention conducted, the awareness rate of
      AIDS related knowledge for MSM increased. Though the rate of anal sex increased
      after intervention, the rate of condom use in anal sex increased, too. The rate
      of condom use decreased after receiving more than 3 interventions. Data from the
      multivariate GEE analysis indicated that protective factors might be as follows:
      education level of college and above (aOR=0.81, 95%CI: 0.68-0.98), awareness of
      AIDS related knowledge (aOR=0.52, 95%CI: 0.36-0.75), ever receiving condom
      promotion and distribution in the past six months (aOR=0.60, 95%CI: 0.49-0.74),
      being recruited from mobile internet (aOR=0.85, 95%CI: 0.73-1.00) and times of
      cumulative intervention: one time (aOR=0.55, 95%CI: 0.45-0.66), two times
      (aOR=0.38, 95%CI: 0.30-0.49), three times (aOR=0.26, 95%CI: 0.20-0.35), four
      times and above (aOR=0.24, 95%CI: 0.17-0.33). Diagnoses of STDs in the past six
      months (aOR=1.43, 95%CI: 1.06-1.96), using rush-poppers (aOR=1.22, 95%CI: 1.02
      1.47) might be risk factors. Conclusions: After continuous behavior intervention,
      the incidence of HIV infection and syphilis were at a low level in the MSM cohort
      in Tianjin. Their awareness rate of AIDS related knowledge and the rate of condom
      use increased. But there are still many risk factors influencing the unprotected
      anal sex in MSM. We should continuously carry out behavioral intervention
      programs to prevent unprotected anal sex among MSM.

PMID- 30293314
TI  - [Abuse of diphenoxylate and related factors of forced drug abstainer in Gansu
      province].
AB  - Objective: To investigate the prevalence of diphenoxylate abuse and related
      factors of forced drug abstainer in Gansu province. Methods: By using a self
      designed questionnaire, an epidemiologic investigation was carried out among 2
      108 forced drug abstainer selected from the compulsory isolation detoxification
      center of Gansu province. A case-control study was conducted to analyze the
      factors related with diphenoxylate abuse. Results: The diphenoxylate abuse rate
      among forced drug abstainer in Gansu was 19.8% (406/2 046), ranking first in
      medical drug abuse. Multiple logistic regression analysis showed that factors as
      relieving withdrawal symptoms (OR=2.08, 95%CI: 1.01- 4.32), ways to obtain
      diphenoxylate (other ways: OR=1.00; regular clinic: OR=27.67, 95%CI: 2.64-289.82;
      friend: OR=0.01, 95%CI: 0.01-0.03), degree of euphoria (high: OR=1.00; medium: OR
      =3.36, 95%CI: 1.18-9.55; low: OR=26.16, 95%CI: 10.30-66.42), years of drug abuse
      (<5 years: OR=1.00; 10-15 years: OR=2.48, 95%CI: 1.02-6.04), abuse at home or in
      friend's house (OR=3.04, 95%CI: 1.08-8.68), abuse in car (OR=0.05, 95%CI: 0.00
      0.68) and detoxification for the first time (OR=0.61, 95%CI: 0.43-0.86) were the
      possible influencing factors for diphenoxylate abuse. Conclusions: The prevalence
      of diphenoxylate abuse in forced drug abstainer in Gansu was relatively high.
      Reasons of abusing, the way to obtain diphenoxylate, whether using drug together
      with friends, degree of euphoria, years of abuse, abuse place and times for
      detoxification were related factors influencing the abuse of diphenoxylate.

PMID- 30293316
TI  - [Current status of national free antiretroviral therapy in interprovincial
      migrating people living with HIV/AIDS and influencing factors, China, 2011-2015].
AB  - Objective: To understand the current status of national free antiretroviral
      therapy in interprovincial migrating people living with HIV/AIDS (PLWHA) and
      influencing factors in China. Methods: Descriptive and trend test analyses were
      performed to evaluate the historical characteristics and trends of main
      descriptive indicators on national free antiretroviral therapy for the
      interprovincial migrating PLWHA by using the data collected from National
      Comprehensive HIV/AIDS Information System from 2011 to 2015. Logistic regression
      model was used to explore the main factors that influencing the coverage of
      national free antiretroviral therapy among the interprovincial migrating PLWHA in
      China. Results: The proportion of interprovincial migrating PLWHA gradually
      increased in last 5 years from 7.1% (17 784/250 645) in 2011 to 10.3% (54 596/528
      226) in 2015 (Z=51.38, P<0.000 1) in China. The coverage rate of free
      antiretroviral therapy in interprovincial migrating PLWHA increased from 37.3% (6
      641/17 784) in 2011 to 71.0% (38 783/54 596) in 2015, showing a significant
      rising tendency (Z=96.23, P<0.000 1), but it was slightly lower than that in non
      interprovincial migrating PLWHA in 2015 (71.5%, 338 654/473 630). Multivariate
      logistic regression analysis showed that the PLWHA who were females, aged >=50
      years, of Han ethnic group, married or had spouse, had the educational level of
      high school or above, infected through homosexual intercourse, with CD(4)(+)T
      cells counts <=500 cells/MUl at the first visit, identified to be infected with
      HIV in medical setting, living in urban areas et al, were more likely to receive
      free antiretroviral therapy. Conclusions: The coverage rate of free
      antiretroviral therapy varied among the interprovincial migrating PLWHA with
      different characteristics. It is still necessary to take effective measures to
      further increase the coverage of free antiretroviral therapy in interprovincial
      migrating PLWHA and to include the free antiretroviral therapy in interprovincial
      migrating PLWHA into standardized management system as soon as possible.

PMID- 30293317
TI  - [Analysis on cardio-metabolic related risk factors in farmers of 15 provinces in
      China].
AB  - Objective: To analyze the prevalence and co-prevalence of cardio-metabolic
      related risk factors in farmers aged >=18 years in China, to explore the
      influence of population economic factors on them. Methods: A total of 3 367
      farmers, including fishermen or hunters, aged >=18 years were selected as study
      subjects from the database of Nutritional Status and Health Transition of Chinese
      Residents Project in 2015. Basic information (age, gender), data on
      anthropometric (body height, weight and waist size), blood biochemical and
      socioeconomic (occupation, income, education level and living area) were
      included. According to the definition of the metabolic syndrome released by the
      International Diabetes Federation (IDF) in 2005, five cardio-metabolic risk
      factors appeared as central obesity, increased triglycerides, decreased HDL-C,
      increased blood pressure and increased plasma glucose. Co-prevalence of risk
      factors was defined as detecting 2 or more risk factors in a person at the same
      time. Multivariate logistic regression model was used to analyze the relationship
      between socioeconomic factors and metabolic risk factors. Results: In 3 367
      framers of 15 provinces (autonomous region and municipality), the prevalence
      rates of central obesity, increased blood pressure, increased plasma glucose,
      increased triglycerides and decreased HDL-C were 51.8%, 59.0%, 17.0%, 25.5% and
      38.7% respectively. Multivariate logistic regression analysis showed that the
      risks for central obesity (OR=3.69, 95%CI: 3.17-4.28) and decreased HDL-C
      (OR=3.28, 95%CI: 2.81- 3.82) were higher in women than in men, and the risks for
      increased blood pressure (OR=0.73, 95%CI: 0.63-0.84), increased blood glucose
      (OR=0.80, 95%CI: 0.67-0.97) were lower in women than in men. Age was positively
      correlated with the prevalence or co-prevalence of metabolic risk factors (trend
      P<0.05). Framers in western China had obviously lower risk for central obesity
      compared with farmers in central China. No significant correlation was found
      between farmers' income level, education level or the prevalence of metabolic
      risk factors. Conclusion: In 15 provinces of China, the prevalence of at least 1
      kind of cardio-metabolic risk factor was found in 85.5% of the farmers, and the
      co-prevalence of cardio-metabolic risk factor was found in 60% of farmers. The
      prevalence and co-prevalence of cardio-metabolic risk factors were significantly
      associated with age and gender. It is suggested to take targeted nutritional
      intervention and health education according to the distribution characteristics
      of prevalence and co-prevalence of cardio-metabolic factors and strengthen the
      early prevention and control programs of the diseases.

PMID- 30293318
TI  - [Study on the status of frailty and related determinants among the elderly in
      China].
AB  - Objective: To investigate the frailty status and related determinants among the
      elderly in China. Methods: Frailty index (FI) was applied to evaluate the frailty
      status of the elderly. Data used in this study was from the China Health and
      Retirement Longitudinal Study (CHARLS) in 2011-2015. Binary logistic regression
      analysis was carried out to identify the determinants related to the status on
      frailty. Results: The prevalence rates of frailty in the elderly were 18.7%,
      20.6% and 28.4% in 2011, 2013 and 2015, respectively. Being female or elderly
      under advanced age, were both associated with the higher level of FI. Factors as
      hip fracture, falls, alcohol intake more than once a month, and less
      participation in social activities etc., might serve as the risk factors for
      frailty. Conclusion: Chinese elderly showed relatively high prevalence on frailty
      and with annual increasing trend. The status of frailty was related to factors as
      adverse events and unhealthy lifestyles. Comprehensive intervention strategies
      should be adopted in early life of the elderly to delay the development process
      of frailty.

PMID- 30293319
TI  - [Estimation on the health life expectancy of adults in Zhejiang province, 2016].
AB  - Objective: To estimate the health-adjusted life expectancy (HALE) of adults in
      Zhejiang province and evaluate the health status of the adults. Methods: This
      study was based on the mortality data collected from Zhejiang Chronic Disease
      Surveillance Information and Management System, and mortality rates from the
      underreporting survey and self-reported health data in 2016. Hierarchical Ordered
      Probit (HOPIT) model was used to estimate the severity-weighted prevalence of
      disability. Sullivan's method was used to calculate the HALE. Results: After
      adjustment by HOPIT model, the severity-weighted prevalence of disability
      increased significantly with age (chi(2)=5 795.81,P<0.001), and it was higher in
      females than in males (chi(2)=5 353.27, P<0.001). The life expectancy and self
      evaluated HALE were 59.08 years and 48.68 years, respectively, in those aged >=20
      years, the difference was 10.40 years due to disability. The proportion of HALE
      loss due to disability in the total life expectancy was 17.61%, and it increased
      with age. HALE was higher in males than in females (49.21 years vs. 48.14 years),
      and in urban residents than in rural residents (49.92 years vs. 47.43 years).
      Conclusion: The proportion of loss of HALE in the total life expectancy in adults
      was high in Zhejiang, and it higher in males than in females, in urban residents
      than rural residents. Programs on improving health care in women and rural
      residents should be promoted.

PMID- 30293320
TI  - [Analysis on influencing factors that leading to nonspecific responses to
      indeterminate results of HIV antibodies].
AB  - Objective: To identify the influencing factors that leading to nonspecific
      responses to indeterminate HIV antibody tests, to provide scientific evidence for
      the differential diagnosis of HIV infection and control strategy. Methods: A case
      control study was conducted. The samples of HIV antibody indeterminate in
      confirmed Western blot (WB) tests, but were negative in HIV nucleic acid tests,
      were collected as HIV antibody indeterminate group from WB results of HIV
      confirmatory laboratories of Fujian province in 2015-2016. The general population
      matched group with HIV antibody screening negative samples and WB negative
      matched group with WB negative samples were selected as the two compared groups
      by matching gender and age from HIV antibody screening in Fujian province in the
      same period. Blood concentrations of hepatitis B surface antigen (HBsAg), anti
      hepatitis C virus (HCV) antibody, anti-treponema pallidum (TP) antibody,
      antinuclear antibody (ANA), anti-human T-cell leukemia virus (HTLV) antibody, and
      alpha-fetoprotein (AFP) were detected by using enzyme-linked immunosorbent assay
      (ELISA). chi(2) test and multivariate non-conditional logistic regression
      analysis were performed to identify the influencing factors that leading to
      nonspecific responses, to indeterminate HIV antibody tests. Results: A total of
      13 WB band patterns were observed in 110 HIV antibody indeterminate samples, in
      which a single p24 band (58.18%, 64/110), a single gp160 band (17.27%, 19/110)
      and a single p17 band (7.27%, 8/110) were the three most common patterns. The
      positive rate of anti-TP antibody was significantly higher in HIV antibody
      indeterminate samples than general population control group and WB negative
      control group (10.91%, 12/110 vs. 1.77%, 4/226 and 3.64%, 4/110), compared with
      two control groups (chi(2)=13.627 and 4.314, P<0.05). The positive rate of AFP
      was significantly higher in HIV antibody indeterminate samples than general
      population control group (18.18%, 20/110 vs. 0.44%, 1/226, chi(2)=39.736,
      P<0.05), the different was not significant compared with WB negative control
      group (18.18%, 20/110 vs. 23.64%, 26/110, chi(2)=0.990, P>0.05) While no
      significant differences were found between HIV antibody indeterminate group and
      two control groups in terms of the positive rates of ANA, HBsAg, anti-HCV
      antibody or anti-HTLV antibody. Conclusions: The influencing factors that leading
      to nonspecific responses to indeterminate HIV antibody tests appeared complicate,
      and the anti-TP antibody positivity might be an influencing factor responsible
      for nonspecific responses to indeterminate HIV antibody tests.

PMID- 30293321
TI  - [Association between nuclear factor kappa-light-chain-enhancer of activated B
      cells genetic polymorphisms and HCV susceptibility among the Chinese population
      under high-risk].
AB  - Objective: To explore the association between nuclear factor kappa-light-chain
      enhancer of activated genetic polymorphisms in B cells (NF-kappaB) and the HCV
      susceptibility, among the Chinese population. Methods: A total of 1 679
      participants were enrolled; including 503 drug users and 1 176 other participants
      at risk under the exposure for blood. By using the logistic regression analysis,
      related risk factors for HCV infection among subjects were analyzed. Two NF
      kappaB pathway variants, NF-kappaB1 rs72696119 and REL rs13031237 were then
      genotyped by TaqMan assay method. Logistic regression analysis was performed to
      analyze the association between gene polymorphisms and the susceptibility on HCV.
      Results: Among the drug users, women (OR=0.408, 95%CI: 0.308-0.767) appeared to
      be associated with the decreased risk for HCV infection, while factors as drug
      injection (OR=8.817, 95%CI: 5.577-13.937) and the duration of drug-intake >5.5
      years (OR=2.891, 95%CI: 1.824-4.583) were associated with the increased risk for
      HCV infection. Among the participants who had been exposed to blood, women
      (OR=3.431, 95%CI: 2.360-4.988) were associated with the increased risk for HCV
      infection, while the levels of education beyond elementary school (OR=0.613,
      95%CI: 0.429-0.876) were associated with the decreased risk for HCV infection.
      Compared to the reference NF-kappaB1 rs72696119 CC genotype, the carriage of GG
      genotype was associated with an increased risk of susceptibility on HCV
      (OR=1.412, 95%CI: 1.035-1.927) among the total study population. Results from the
      interaction analysis showed that there was no interactive effects appeared
      between rs72696119 and route of infection, or between rs72696119 and gender among
      the total population under study (all P>0.05). Conclusion: NF-kappaB1
      polymorphism rs72696119 and related factors seemed associated with the
      susceptibility to HCV infection among high-risk Chinese populations.

PMID- 30293322
TI  - [Association between AOX1, IRF4 methylation in peripheral blood leukocyte DNA and
      the risks of breast cancer: a case-control study].
AB  - Objective: To understand the relationship between AOX1, IRF4 gene methylation
      status in peripheral blood leukocyte DNA, as well as its interaction with
      environmental factors, and the risk of breast cancer. Methods: A case-control
      study was conducted among 401 breast cancer patients and 555 cancer-free controls
      selected from 2010 to 2014. Methylation sensitive-high resolution melting curve
      analysis was used to detect the methylation status of AOX1 and IRF4. The
      multiplication interaction effect between genes' methylation and environmental
      factors on the risk of breast cancer was analyzed by using unconditional logistic
      regression, and Excel software was used to analyze the additive interaction
      effect. Results: Individuals without AOX1 methylation had a 1.37-fold (95%CI:
      1.02-1.84) higher breast cancer risk compared to individuals with AOX1
      methylation. AOX1 methylation interacted with fungi intake (OR=2.06, 95%CI: 1.12
      3.79) and physical activity (OR=2.18, 95%CI: 1.16-4.09) synergistically, on the
      risk for breast cancer, but no additive interaction effects were observed. Non
      methylation of IRF4 could increase the risk for breast cancer, with statistical
      significance (OR=1.71, 95%CI: 0.99-7.43). Neither multiplication nor additive
      interactions were observed between IRF4 methylation and environmental factors.
      Conclusion: Non-methylation of AOX1 and IRF4 were a risk factors for breast
      cancer.

PMID- 30293323
TI  - [Correlation between pregnancy-induced hypertension and age in pregnant women
      from Hebei province, 2016].
AB  - Objective: To analyze the correlation between age and pregnancy-induced
      hypertension (PIH) in pregnant women from Hebei province in 2016. Methods: A
      retrospective analysis was conducted by using the clinical data of 64 909
      pregnant women, delivering in 22 hospitals in Hebei in 2016. Descriptive
      statistics was used to describe the general data and pregnancy outcomes of
      pregnant women, and chi(2) test was used to compare the incidence of PIH in
      different age groups, and logistic regression analysis was used to analyze the
      risk factors for PIH. Results: The incidence of PIH was lowest in 20-29 year old
      women, and increased obviously in those aged<20 and>35 years (P<0.05), and the
      incidence was positively correlated with age. Logistic regression analysis showed
      that age, times of pregnancy, number of previous cesarean section and fetus
      number of current pregnancy were the risk factors for PIH (OR=1.293, 1.153,
      1.307, 3.607), while times of deliver and times of prenatal examination were the
      protective factors (OR=0.655, 0.951). Conclusion: Advanced age pregnancy and
      young age pregnancy would significantly increase the incidence of PIH. Prenatal
      care should be strengthened for pregnant women at risk for PIH.

PMID- 30293324
TI  - [A systematic review on blood biomarkers of neurocognitive disorders in HIV
      infected individuals].
AB  - Biomarkers are very useful in the diagnosis and identification of neurocognitive
      impairments (NCIs) or disorders (NCDs) in HIV-infected individuals, and in
      particular, blood biomarkers have become more promising because they are cheap
      and easy to obtain or accept. A systematically literature retrieval was conducted
      by using PubMed, CNKI, Wanfang and VIP databases for studies about blood
      biomarkers of neurocognitive impairment of HIV-infected individuals in 2008-2017,
      according to the inclusion and exclusion criteria. Finally, a total of 43 related
      articles were included for this systematic review for the purpose of providing
      scientific evidence for further research and clinical practices.

PMID- 30293325
TI  - [The Wuhan Twin Birth Cohort Study].
AB  - The prevalence of child and adolescent growth and mental-behavior related
      diseases are increasing, and the pathogenesis are complex. Twins are excellent
      natural resources for complex chronic diseases research as they share the
      maternal intrauterine environment, born at the same time and share the same
      family environment in early years, which could benefit the adjust ment of
      confounding factors, such as age, genetic factors and early family environmental
      factors. Birth cohort with twin families involved could be more effective in
      exploring the genetic and environmental factors for complex chronic diseases at
      the very beginning of life. This paper summarizes the objective, content,
      progress, strengths and potential problems of Wuhan Twin Birth Cohort, with
      emphasis on the overall design and progress of the study.

PMID- 30293327
TI  - [Artificial intelligence in neurology: present and future].

PMID- 30293326
TI  - [Discussion on implementation of public health standards adopted in centers for
      disease control and prevention].
AB  - As the most important phase in standardization activity, implementation saves as
      the essence. CDC in China are the major institutions undertaking disease control
      and prevention. Implementing the standards of public health provides technical
      basis for CDC to complete the task of disease control and prevention. In the
      study, spot conversation and questionnaire were used to investigate the
      implementation of standards on public health in CDC. Results showed that the
      staff of CDC got to know the standards through the Internet. The departments of
      CDC which conducted training and sent staff to attend training courses accounted
      for 50.00%(25/50) and 34.00%(17/50), respectively. State mandatory rule is still
      the main reason for relevant departments to implement the standards of the public
      health. Government promotion activities facilitate the implementation of
      Standards, and the degree of familiarity with Standards affects the
      implementation as well. The paper summarizes the existing problems, such as the
      lack of coordination between departments of public health at provincial level or
      below, lack of access to standards, and the need to strengthen the training of
      the standard implementation etc. It puts forward some suggestions to strengthen
      the implementation of public health Standards.

PMID- 30293328
TI  - [Tauopathy: the gradually concerned neurodegenerative diseases].

PMID- 30293329
TI  - [Turning the gaze: challenges of imaging differentiation and multidisciplinary
      combined diagnosis on tumefactive demyelinating lesions].

PMID- 30293330
TI  - [Guidelines on the management of hepatic encephalopathy in cirrhosis].
AB  - The Chinese Society of Hepatology developed the current guidelines on the
      management of hepatic encephalopathy (HE) in cirrhosis based on the published
      evidences and panelists' consensus. The guidelines provided recommendations for
      the diagnosis and management of hepatic encephalopathy including minimal hepatic
      encephalopathy (MHE) and overt hepatic encephalopathy (OHE) emphasizing the
      importance on screening MHE in patients with end-stage liver diseases. The
      guidelines emphasized that early identification and prompt treatment are
      essential to improve the prognosis of HE. The principles of treatment mainly
      consist of eliminating precipitating factors, treating hyperammonemia to improve
      acute neuropsychiatric abnormalities rapidly, primary and secondary prophylaxis.

PMID- 30293331
TI  - [Chinese expert-based consensus for methotrexate in rheumatic diseases].
AB  - To establish the experts consensus on the use of methotrexate in the treatment of
      rheumatic diseases. A consensus development panel was established. The panel of
      consensus was composed of 45 experts in rheumatology from the group of Chinese
      Association of Rheumatology and Immunology Physicians. The consensus development
      panel developed 7 recommendations, including the clinical status and application
      principles of methotrexate in the treatment of rheumatoid arthritis, optimal
      dosage and route, dosage adjustment, monitoring, long-term safety and management
      in the perioperative period and before/during pregnancy. This consensus was
      intended to standardize the use of methotrexate in rheumatic diseases and improve
      the management of rheumatoid arthritis and other rheumatic diseases.

PMID- 30293332
TI  - [The association of lipid profile and bleeding in patients with minor stroke or
      transient ischemic attack on antiplatelet therapy: subgroup analysis of CHANCE].
AB  - Objective: Abnormalities of lipid profile were considered as risk factors of
      hemorrhage after ischemic stroke. We aimed to determine the relationship between
      lipid levels and bleeding in minor stroke or transient ischemic attack (TIA)
      patients receiving antiplatelet therapy. Methods: Serum total cholesterol, low
      density lipoprotein cholesterol, high-density lipoprotein cholesterol and
      triglyceride were tested in a subgroup of 3 044 consecutive patients from
      Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events
      (CHANCE) trial. Patients were randomized to clopidogrel plus aspirin group or
      single aspirin group. The primary endpoint was any bleeding within 90 days. The
      secondary endpoint was severe bleeding according to the Global Utilization of
      Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries
      (GUSTO) definition. Cox proportional hazards models were used to assess the
      associations of lipid levels and outcomes. Results: A total of 59 (1.9%) bleeding
      events occurred at 90 days. High-density lipoprotein cholesterol (adjusted
      HR=2.16; 95%CI 1.17-4.00, P=0.014) and age (adjusted HR=1.04; 95%CI 1.01-1.06,
      P=0.006) were significantly associated with any bleeding. High-density
      lipoprotein cholesterol was also associated with severe bleeding (adjusted
      HR=3.05; 95%CI 1.39-6.68, per 1 mmol/L increase). No correlations between
      outcomes and levels of total cholesterol, low-density lipoprotein cholesterol and
      triglyceride were found. There was no interaction of any lipid component level
      with randomized antiplatelet therapy. Conclusions: Elevated high-density
      lipoprotein cholesterol is independently associated with any bleeding and severe
      bleeding in the patients with acute minor stroke or high-risk TIA on antiplatelet
      therapy.

PMID- 30293333
TI  - [The efficacy of cognitive behavioral therapy in insomnic patients with or
      without comorbidities: a pilot study].
AB  - Objectives: To evaluate the effectiveness of cognitive behavior therapy for
      insomnia (CBT-i) in chronic insomnia patients in terms of the improvements of
      psychological and sleep diary parameters. Methods: Patients who met the
      diagnostic criteria of chronic insomnia, were divided into primary group or
      comorbid group. Both groups received standard CBT-i interventions. Psychological
      scales and sleep diaries were used to evaluate participants' severity of insomnia
      and psychological conditions related to insomnia at four time points: before
      intervention (baseline), immediate after intervention, 4 weeks and 16 weeks after
      intervention. Results: Both groups achieved significant improvements after
      intervention on psychological measurements and sleep diary parameters. Such
      improvements were maintained at 4-week and 16-week follow-ups. The sleep diary
      data indicated that by the end of the intervention, there were significant
      differences on sleep onset latency (51.72 min to 10.53 min in primary group,
      P<0.01; 59.26 min to 15.67min in comorbid group, P<0.01) and sleep efficiency
      (71% to 95% in primary group, P<0.01; 68% to 90% in comorbid group, P<0.01).
      There were differences on sleep onset latency (10.00 min vs. 13.93 min, P<0.05),
      total sleep time (355.71 min vs. 327.85 min, P<0.05) and sleep efficiency (95%
      vs. 91%, P<0.01) in primary group and comorbid group respectively. No differences
      were found on wake after sleep onset in the two groups. Conclusions: Chronic
      insomnia patients with or without comorbidities both have improvements after CBT
      i. Sleep diary parameters rather than psychological measurements are different in
      two groups. Thus, CBT-i is an effective non-pharmaceutical therapy inpatients
      with chronic insomnia.

PMID- 30293334
TI  - [The clinical significance of circulating follicular helper T cells in patients
      with anti-neutrophil cytoplasmic myeloperoxidase antibody-associated vasculitis].
AB  - Objective: To investigate the change of circulating follicular helper T cells
      (cTfh) in patients with anti-neutrophil cytoplasmic myeloperoxidase antibody
      associated vasculitis (MPO-AAV), and to analyze the relationship between cTfh and
      disease activity. Methods: Thirty-eight untreated MPO-AAV patients (patient
      group) and thirty-eight healthy volunteers (control group) were enrolled in this
      study. cTfh and membrane expression of inducible co-stimulator (ICOS) and
      programmed cell death protein 1 (PD-1) were detected by flow cytometry (FCM).
      Serum anti-neutrophil cytoplasmic myeloperoxidase antibody (MPO-ANCA) was
      measured by ELISA. Disease activity was evaluated by Birmingham vasculitis
      activity score (BVAS). Results: Compared with those in control group, the
      proportions of cTfh, ICOS(+)Tfh and PD-1(+) Tfh cells in patient group were
      significantly higher [(25.9+/-3.8)% vs. (21.0+/-5.3)%, P<0.001; (1.8+/-0.8)% vs.
      (0.8+/-0.5)%, P<0.001 and (10.2+/-2.8)% vs. (8.2+/-2.2)%, P=0.001, respectively].
      Meanwhile, the expression of ICOS and PD-1 on cTfh in patient group was markedly
      more intensive (59.6+/-10.0 vs.49.2+/-6.9, P<0.001 and 532.6+/-104.2 vs. 485.1+/
      73.4, P=0.025, respectively). In patient group, the proportion of cTfh was
      positively correlated with the ratio of ICOS(+)Tfh, the expression of ICOS, the
      level of MPO-ANCA and BVAS (r=0.407, P=0.011; r=0.705, P<0.001; r=0.737, P<0.001
      and r=0.663, P<0.001, respectively). The expression intensity of ICOS on cTfh was
      positively associated with ICOS(+)Tfh ratio, serum MPO-ANCA and BVAS (r=0.388,
      P=0.016; r=0.645, P<0.001 and r=0.653, P<0.001, respectively). Nevertheless, the
      expression of PD-1 on cTfh was only positively correlated with the ratio of PD
      1(+) Tfh (r=0.473, P=0.003). Conclusions: Enhanced cTfh in patients with MPO-AAV
      might produce MPO-ANCA, which is related to the aggravation of MPO-AAV. Thus,
      cTfh and its ICOS could be potentially targeted for the treatment of MPO-AAV.

PMID- 30293335
TI  - [Diversity analysis of luminal and mucosa-associated microbial communities in
      obese mice].
AB  - Objective: Gut microbiota have been reported to be able to regulate host
      metabolism and is closely associated to obesity. The purpose of this study was to
      explore the differences between the diversity of luminal and mucosa-associated
      microbial communities in obese mice. Methods: Colonic luminal contents and
      colonic mucosa were separately collected from 10 obese mice fed with high-fat
      diet for 12 weeks. DNA of gut microbiota was extracted and micro flora
      populations were analyzed by Illumina sequencing. Species annotation, diversity
      analysis, and species difference analysis were conducted. Results: The microbial
      flora from colonic contents had similar richness, evenness and overall structure
      to those from colonic mucosa (ACE index 250 vs. 285, Chao index 257 vs. 291,
      Shannon index 3.84 vs. 3.97, Simpson index 0.05 vs. 0.06, all P>0.05). However,
      there were differences in the microbial composition on specific levels. At the
      phylum level, colonic contents had higher abundance of Bacteroidetes (56.08% vs.
      27.25%, P=3.21*10(-5)), while colonic mucosa had higher abundance of Firmicutes
      (49.09% vs. 34.27%, P=0.03) and proteobacteria (18.48% vs. 3.62%, P=0.000 9). At
      the genus level, butyrate-producing bacteria-Lactobacillus was more abundant in
      colonic content (LDA score=3.89), whereas gram-negative genus Helicobacter,
      Sphingomonas and Desulfovibrio were relatively abundant in colonic mucosa (LDA
      score=4.78, 3.59 and 4.11, respectively). Conclusion: There were differences in
      microbial composition at the phylum and genus levels between microbial flora from
      colonic contents and colonic mucosa, although they had similar richness, evenness
      and overall structure.

PMID- 30293336
TI  - [The clinical analysis of diabetic patients with chronic inflammatory
      demyelinating polyradiculoneuropathy].
AB  - To explore clinical characteristics, electrophysiological findings and treatment
      response in diabetic patients with chronic inflammatory demyelinating
      polyradiculoneuropathy (DM-CIDP). Thirty-six CIDP patients were identified, 10
      were DM-CIDP and 26 were non-DM-CIDP. Clinical medical records,
      electrophysiological data and treatment were retrospectively reviewed. DM-CIDP
      patients were significantly older than non-DM-CIDP patients [(56.7+/-10.0) years
      old vs. (40.4+/-16.9) years old, P=0.001]. However, clinical characteristics and
      abnormalities of electrophysiological tests in both groups were comparable. DM
      CIDP subjects responded to corticosteroids or intravenous immunoglobulin, thus
      with better prognosis.

PMID- 30293337
TI  - [The influence of gender on clinical manifestations of primary
      hyperparathyroidism].
AB  - To explore the impact of gender on presentation of primary hyperparathyroidism
      (PHPT), clinical data of 150 histopathologically proven PHPT patients were
      collected and retrospectively analyzed. Most of the patients (72.0%) were
      parathyroid adenoma (PA), and 9.3% of them were parathyroid carcinoma (PC). In PA
      patients, albumin-corrected serum calcium levels (TASC) were lower in women than
      in men [ (2.84+/-0.28) mmol/L vs. (3.03+/-0.34) mmol/L, P=0.006]. In all PHPT
      subjects, serum urea nitrogen, creatinine, uric acid levels were lower in women
      than in men. Bone pain was more frequent in women over 50 years old than in men
      (52.33% vs.29.17%, P=0.045). The incidence of PC was higher in men than in women
      (20.59% vs. 6.03%, P=0.010). In conclusion, there are gender differences in the
      clinical presentation of PHPT. TASC was high in men with PA compared to women
      with PA. Bone pain was more common in the woman patients over 50 years old, and
      PC was more common in men.

PMID- 30293338
TI  - [Necrotizing autoimmune myopathy associated with Sjogren syndrome: report of 2
      case].

PMID- 30293339
TI  - [Frequently asked questions of gout(2): prophylaxis and treatment of acute gout].

PMID- 30293340
TI  - [The diagnostic and therapeutic significance of quantitative detection of serum
      procalcitonin in patients with pulmonary infections].

PMID- 30293341
TI  - [Advances in globular glial tauopathies].

PMID- 30293342
TI  - [Airway driving pressure and lung protective ventilation in acute respiratory
      distress syndrome patients].

PMID- 30293343
TI  - [Comments on the Society of Thoracic Surgeons clinical practice guidelines on
      arterial conduits for coronary artery bypass grafting].

PMID- 30293344
TI  - [Study on the negative regulation of TIPE2 from peripheral blood mononuclear
      cells on tissue factor in patients with bronchial asthma].
AB  - Objective: To investigate the expression of tumor necrosis factor alpha-inducible
      protein 8 like-2 (TIPE2) and tissue factor (TF) in patients with bronchial
      asthma. And to explore the regulation of TIPE2 on TF. Methods: Sixty-five
      asthmatic patients and 40 healthy controls were selected from the First
      Affiliated Hospital of Zhengzhou University from July to November, 2017. The
      expression of TIPE2 and TF in peripheral blood mononuclear cells of asthmatic
      patients and healthy controls were detected by Western blot.The level of TF
      protein in plasma was detected by enzyme-linked immunosorbent assay. The changes
      of TIPE2 and TF mRNA expression in THP-1 cells stimulated by house dust mite
      extract were detected by real-time fluorescence quantitative PCR (RT-PCR). The
      recombinant adenovirus Adv-TIPE2 was constructed and transfected into THP-1 cells
      and the effect of over-expression TIPE2 on TF expression in THP-1 cells was
      detected by RT-PCR. Results: The relative level of TIPE2 protein in asthmatic
      patients and healthy controls was 0.025+/-0.010 and 0.087+/-0.070, while that of
      TF was 0.40+/-0.27 and 0.15+/-0.10, respectively. Compared with healthy controls,
      the levels of TIPE2 protein decreased and TF protein increased in asthmatic
      patients, the differences were statistically significant (t=-5.06, 9.04, P<0.05)
      . TIPE2 protein level was negatively correlated with TF protein level (r=-0.460
      3, P<0.05). The house dust mite extract reduced the expression level of TIPE2
      mRNA in THP-1 cells, but increased the level of TF mRNA expression. When the
      concentration was 1 MUg/ml, the change of TIPE2 mRNA was the most obvious at 4 h
      (P<0.05). The recombinant adenovirus Adv-TIPE2 was successfully constructed. The
      level of TF mRNA expression in THP-1 cells over-expressing TIPE2 gene was reduced
      (P<0.05). Conclusion: TIPE2, a negative regulator of inflammation, has a negative
      control effect on TF, and may be involved in the hyper-coagulable state of
      bronchial asthma by regulating TF expression.

PMID- 30293345
TI  - [Analysis on the distribution and drug resistance features of anaerobes isolated
      from clinical infectious specimens].
AB  - Objective: To clarify distribution and drug resistance characteristics of
      anaerobes isolated from clinical infectious samples, and to provide experimental
      data for guiding on treatment of infections caused by anaerobes. Methods: The
      anaerobes, isolated from 1 057 different clinical specimens from inpatients
      admitted to the Affiliated Hospital of Inner Mongolia Medical University from
      March 2016 to November 2017, were identified by VITEK-2 anaerobes and
      corynebacterium (ANC) card and bacteroides fragilis isolates were further
      verified by 16S-rRNA sequencing. Meanwhile, broth dilution method was employed to
      detect the drug sensititities of bacteroides fragilis and PCR method was used to
      detect the carbapenem resistance gene cfiA. Results: Totally 303 strains of
      anaerobic bacteria were isolated, among which 199 strains were gram-negative
      bacteria, accounted for 65.68%. Among the gram negative anaerobes, bacteroides
      species were the most common, accounted for 35.64%, followed by prevotella spp.,
      which accounted for 19.14%. B. fragilis were the most common among Bacteroides
      spp., accounted for 21.54%, followed by Prevotella bivia, accounted for 5.94%.
      The coincidence rate of 16S-rRNA sequencing results of Bacteroides fragilis and
      that of ANC card identification results was 100% (65/65). The drug resistance of
      B. fragilis to penicillin, clidamycin, ampicillin/sulbactam,
      amoxicillin/clavulanic, were 100%, 90.77%, 56.92% and 66.67%, respectively. The
      resitance rate of B. fragilis to chloramphenicol was the lowest, which was
      1.54%.Moreover, the resistance rate of B. fragilis to imipenem and metronidazole
      were both higher, which were 38.46%(25/65) and 23.08%(15/65), respectively, and
      the positive rate of beta lactamase was 100% (65/65). The carrying rate of
      carbapenems resistance gene cfiA for 65 strains of Bacteroides fragilis was 52.3%
      (34/65), and 72.00%(18/25)for imipenem resistant strains. Conclusions: The
      obligate anaerobic bacteria are widely distributed in clinical specimens, and the
      great majority are gram negative anaerobic bacteria, and the most frequently
      isolated one is Bacteroides fragilis. Bacteroides fragilis isolates are found to
      be resistant to several kinds of common antibiotics, especially for imipenem and
      metronidazole, which should be given more attention to.

PMID- 30293346
TI  - [Expression of stem cell markers CD44 and Lgr5 in colorectal cancer and its
      relationship with lymph node and liver metastasis].
AB  - Objective: To investigate the relationship between the expression of stem cell
      markers CD44 and Lgr5 and the clinicopathological features, lymph node and liver
      metastasis, and to analyse the value of both in evaluating the prognosis of
      colorectal cancer. Methods: A total of 90 cases of colorectal cancer, 20 cases of
      adjacent tissues, 30 cases of lymph node metastases, 28 cases of cancer nodules
      and 30 cases of liver metastasis of colorectal cancer were collected from
      Department of Pathology of the Second Hospital of Tianjin Medical University from
      January 2011 to June 2016. The expression of CD44 and Lgr5 protein was detected
      by immunohistochemistry, and the relationship between them and clinical
      pathological data, lymph node metastasis and liver metastasis were analyzed.
      Results: The positive expression rates of CD44 and Lgr5 in colorectal cancer
      tissues were 68.9% and 62.2%, which were significantly higher than 30.0% and
      15.0% of adjacent tissues(P=0.001 and P<0.001). The expression of CD44 and Lgr5
      in colorectal cancer was associated with histological differentiation, depth of
      tumor invasion, lymph node metastasis, soft tissue nodules, hepatic metastasis,
      and TNM staging(P=0.021, 0.032, 0.030, 0.011, 0.015, 0.007 and P=0.011, 0.027,
      0.017, 0.008, 0.011, 0.021). The positive rates of CD44 and Lgr5 expression in
      lymph node metastases, cancer nodules and liver metastases (93.3%, 89.3%, 90.0%,
      and 83.3%, 89.3%, 86.7%) were higher than those in the primary lesions(68.9% and
      62.2%)(P=0.007, 0.032, 0.022 and P=0.033, 0.007, 0.013). There is a positive
      correlation between the expression of CD44 and Lgr5 in colorectal cancer(r=0.615,
      P<0.001), and both positive expression of CD44 and Lgr5 is associated with
      histological differentiation, lymph node metastasis and cancer nodules, liver
      metastasis and TNM staging(P=0.005, 0.003, 0.003, 0.026, 0.014). The Kaplan-Meier
      survival curve showed that the survival rate of positive expression of CD44 and
      both positive expression of CD44 and Lgr5 in patients with colorectal cancer was
      low(P=0.030 and 0.001). Log-rank univariate survival analysis showed that
      histological differentiation, depth of invasion, lymph node metastasis, liver
      metastasis, and clinical stage were the influencing factors of postoperative
      survival time(P=0.035, 0.035, 0.018, 0.016, 0.004). Cox proportional hazards
      regression model multivariate analysis showed that both positive expression of
      CD44 and Lgr5, lymph node metastasis, liver metastasis, and clinical stage were
      independent factors affecting the prognosis of patients with colorectal
      cancer(P=0.004, 0.044, 0.031, 0.008). Conclusions: The expression of CD44 and
      Lgr5 is related to the malignant biological behavior of colorectal cancer, and
      they are important factors in promoting local and distant metastases. Both
      positive expression of them have a hint of bad prognosis.

PMID- 30293347
TI  - [Associated factors of intraoperative hemodynamic instability in patients with
      incidental pheochromocytomas].
AB  - Objective: To analyze the associated factors of intraoperative hemodynamic
      instability (HI) in patients with incidental pheochromocytomas. Methods: The data
      of 104 patients with a pathological diagnosis of pheochromocytoma at Chinese PLA
      General Hospital between January 2011 and December 2016 was retrospectively
      analyzed. The patients were divided into hemodynamic stability (HS) group (n=56)
      and HI group (n=48) according to hemodynamic characteristics. The clinical
      features, biochemical test, preoperative and intraoperative hemodynamics were
      analyzed. Multivariate logistic regression analysis was used to explore the
      associated factors of HI. Results: The age [(44.7+/-12.7) years vs (52.1+/-12.8)
      years], tumor diameter [(47.9+/-16.3) mm vs (57.9+/-21.6) mm], preoperative blood
      pressure [(121.3+/-11.5) mmHg vs (127.2+/-13.3) mmHg] in HS group were less than
      those in HI group (all P<0.05). The proportion of age >= 50 years (28.6% vs
      64.6%), tumor diameter >= 45 mm (48.2% vs 68.8%) and hematocrit < 0.38 (25.0% vs
      51.3%) in HS group were less than that in HI group (all P<0.05). Multivariate
      logistic regression analysis indicated that age >= 50 years (OR=7.940, 95% CI:
      2.480-25.417, P<0.001), tumor diameter >= 45 mm (OR=5.042, 95% CI: 1.482-17.156,
      P=0.010), blood pressure >= 130/80 mmHg (OR=3.127, 95% CI: 1.034-9.463, P=0.044)
      and hematocrit < 0.38 (OR=6.273, 95% CI: 1.893-20.788, P=0.003) were independent
      associated factors of HI. The proportion of HI ( chi(2)=9.033, P=0.003) and
      intensive care unit (ICU) admission ( chi(2)=16.641, P<0.001) increased along
      with increasing associated factors. Conclusion: Adequate preoperative medical
      preparation and volume expansion for appropriate blood pressure are important for
      elder patients with large tumor to prevent HI in patients with incidental
      pheochromocytomas.

PMID- 30293348
TI  - [Clinicopathologic features of lipoprotein glomerulopathy: observation of 6
      cases].
AB  - Objective: To investigate the clinicopathologic features of lipoprotein
      glomerulopathy (LPG). Methods: A total of 6 cases (5 males and 1 female, with a
      mean age of 27.5 years and age range of 11-53 years) of lipoprotein
      glomerulopathy with complete clinicopathologic data were enrolled. Except for
      light microscope, immunofluorescence and electron microscopic examination, renal
      biopsy tissues were checked by oil red O staining. The gene map of apolipoprotein
      E (ApoE) of 2 cases were analyzed. Results: All 6 cases presented with heavy
      proteinuria or nephrotic syndrome, and high level of low-density lipoprotein
      (LDL), very low-density lipoprotein (vLDL), ApoE. Family history of LPG was found
      in 3 cases, and 2 patients progressed to uremia, or even to death. Pathologic
      features showed that lipoprotein deposited in glomerulus capillary lumen and
      renal tubular epithelial cells. Gene analysis demonstrated that 2 cases expressed
      abnormal ApoE gene (162G>C and 455G>C). Conclusions: Lipoprotein glomerulopathy
      is autosomal-recessive disease with mutation of ApoE. Common clinical
      manifestations of LPG are heavy proteinuria or nephrotic syndrome, with a poor
      prognosis. Renal biopsy pathologic diagnosis can confirm this kidney disease.
      Emboli of lipoprotein being observed in glomerulus capillary lumen is the
      pathological feature of LPG.

PMID- 30293349
TI  - [Impact of multiple morphological anomalies of the flagella on the outcomes of
      intracytoplasmic sperm injection for males with infertility].
AB  - Objective: To evalute the clinical outcomes of intracytoplasmic sperm
      injection(ICSI) for infertility male with severe asthenospermia induced by
      multiple morphological anomalies of the flagella (MMAF). Methods: The clinical
      data of 15 patient with MMAF were retrospectively analyzed, who underwent ICSI
      treatment using hyponotic swelling test the "live" sperm in the Department of
      Reproductive Medicine of Yantai Yuhuangding Hospital from January 2011 to
      December 2016. Another 30 obstructive azoospermia (OA)patients are matched
      strictly who also accepted ICSI in the same treatment time. The two groups were
      compared in the couples'age, the body mass index(BMI), the duration of
      infertility, the retrieved oocytes, the number of ICSI oocytes, and the rates of
      fertilization, cleavage, transferrable embryos, good embryos, embryos implanted,
      clinical pregncncy, early abortion, singleton and twins. Results: After 27 cycles
      of ICSI, all of the MMAF patients achieved clinical pregnancy, including 11 cases
      of live birth, 2 cases of spontaneous abortion, and 2 cases of pregnancy
      maintenance. There were no significant difference between MMAF and OA groups in
      the couples'age and BMI, or the numbers of retrieved oocytes and ICSI
      oocytes(P>0.05), but the differences in the infertility duration had statistical
      meaning(P<0.001). No statistical differences were observed among groups in ICSI
      fertility rate(92.0% vs 91.6%), clesvage rate(95.4% vs 96.5%), high-quality
      embryonic rate(56.5% vs 57.5%), good blastocyst rate(23/61 vs 35/94), embryo
      implantation rate(20/48 vs 35/75), early abortion rate(4/19 vs 8/36), clinical
      pregncncy rate(15/27 vs 28/50), singleton rate (10/13 vs 20/25)and twinning
      rate(3/13 vs 5/25)(P>0.05). Conclusions: MMAF may not affect ICSI treatment
      outcomes, but genetic defects can be transmitted through ICSI. The affected
      couples should be informed of the necessity of prenatal genetic diagnosis before
      embryo implantation and the inevitable vertical transmission of genetic problems
      to the offspring.

PMID- 30293350
TI  - [Clinical analysis of hereditary coagulation factor V deficiency].
AB  - Objective: To analyze the clinical characteristics of hereditary coagulation
      factor V deficiency (FVD) and to improve the diagnosis and treatment ability of
      hereditary FVD. Methods: A total of 17 patients with hereditary FVD admitted to
      the Department of Hematology, Peking University People's Hospital from February
      2013 to January 2018 were selected, and their clinical characteristics,
      laboratory examination, treatment and prognosis were retrospectively analyzed.
      Results: There were 9 males and 8 females patients with FVD, the median age was
      36 (1-72 ) years. The median age of men was 39 (1-72)years, and the median age of
      women was 33 (8-56)years. There was no significant difference between them
      (P=0.793). The median prothrombin time(PT) and activated partial thromboplastin
      time(APTT) values were 21.0(13.0-39.6) s and 54.6(38.2-121.2) s, and the median
      level of plasma FV was 8.2% (0.9%-39%). Thirteen cases (13/17) were mild, 3 cases
      (3/17) were moderate, and only 1 case (1/17) was severe according to the FV
      level. Five cases (5/17) had bleeding, including 3 cases with skin ecchymosis, 1
      case with vaginal bleeding, and 1 case with gastrointestinal bleeding. According
      to the severity of bleeding, 1 case (1/17) had severe bleeding, and the other 4
      cases (4/17) were mild bleeding. Conclusions: Patients with hereditary FVD either
      have or do not have bleeding symptoms, with prolonged PT and APTT and decreased
      plasma of FV activity. There is no need for treatment for those without bleeding
      symptoms. Fresh frozen plasma is the first choice for patients who have bleeding,
      and the overall prognosis is good.

PMID- 30293351
TI  - [The epidemiological and clinical characteristics of liver hemangioma in health
      adults].
AB  - Objective: To report the epidemiological and clinical characteristics of liver
      hemangioma in health adults from a large sample of Health Examination Database.
      Methods: A retrospective study was performed to analyze the epidemiological and
      clinical Characteristics of liver hemangioma from people who underwent
      examination in China-Japan friendship hospital from 2014 to 2016. The analysis
      was also included the relationship between gender or age and the incidence and
      tumor size. Results: A total of 83 964 healthy adults (age>=18) were included in
      the study. The overall incidence of liver hemangioma was 2.95%. There was no
      significant difference of liver hemangiomas incidence between male which was
      3.03%, and which was 2.88% in female. Liver hemangiomas incidence had shown
      obviously increased with patients' age, as the evidence indicating that the
      prevalence of liver hemangioma in <30 age group was only 1.87%, and the
      prevalence of liver hemangioma in 41-50 age group raised to 3.72%. While the size
      of liver hemangioma in different genders was also increasing with age, the tumor
      size of liver hemangioma in <30 age group was the smallest. Under 50 years old,
      the size of female patients' liver hemangioma was larger than that of male
      patients in each age group. The size of female patients' liver hemangioma had
      obviously decreased over 60 years old. Conclusion: The progress of liver
      hemangioma was highly influenced by age and gender.

PMID- 30293352
TI  - [Effect of dexmedetomidine on perioperative inflammatory response and cellular
      immune in patients undergoing radical operation of thoracoscopic lung cancer].
AB  - Objective: To evaluate the effect of dexemdetomidine on perioperative
      inflammatory response and cellular immune in patients undergoing radical
      operation of thoracoscopic lung cancer. Methods: One hundred and twenty patients
      undergone radical operation of thoracoscopic lung cancer were randomly divided
      into control group(group B) and dexemdetomidine group(group A), 60 patients in
      each group. They were all implemented one-lung ventilation. In group A,
      dexmedetomidine at a loading dose of 1.0 MUg/kg was intravenously infused
      starting from 20 min before anesthesia induction, followed by continuous infusion
      of 0.5 MUg.kg(-1).h(-1) until 20 min before the end of operation. The equal
      volume of normal saline was given in group B. venous blood samples were collected
      for determination of the serum concentrations of TNF-alpha, IL-6 and IL-8.
      peripheral blood T-lymphocyte subsets(CD(3)(+), CD(4)(+), CD(8)(+),
      CD(4)(+)/CD(8)(+)) and NK cell were also detected at 30 min before anesthesia
      induction(T(0)), at the end of operation(T(1)), 12 h after operation(T(2)) and 24
      h after operation(T(3)). Results: Compared with the T(0, )the plasma
      concentration of TNF-alpha , IL-6 and IL-8 were increased(P<0.05). The levels of
      CD(3)(+) and CD(4)(+), CD(4)(+)/CD(8)(+) ratio and NK cells were decreased in
      both groups at T(1)-T(3)(P<0.05). Compared with group B, the plasma concentration
      of TNF-alpha , IL-6 and IL-8 were decreased more obviously in group A(P<0.05).
      The levels of CD(3)(+) and CD(4)(+), CD(4)(+)/CD(8)(+) ratio and NK cells were
      significantly increased in group A at T(1)-T(3)(P<0.05). Conclusion:
      Dexemdetomidine can decrease perioperative inflarnmatory response and improve
      cellular immune function in the patients undergoing radical operation of
      thoracoscopic lung cancer.

PMID- 30293353
TI  - [Totally endoscopic sublay repair (TES)--a novel approach to repair midline
      ventral hernia].
AB  - Objective: Investigating a novel approach to treat a midline ventral hernia-
      totally endoscopic sublay repair (TES). The procedure will be described in detail
      and the safety and efficacy evaluated. Methods: During July and December 2017,
      eleven consecutive cases of primary and secondary epigastric midline ventral
      hernias were repaired using the TES procedure. A large mesh should be placed in
      the retrorectus position using this minimally invasive procedure. The indications
      for this procedure include umbilical, epigastric and incisional hernia equal in
      length to the rectus diastasis. Results: All operations were successful without
      open conversion. The mean operation time was 120 mins(80-205 min), postoperative
      pain was mild and the mean VAS was 2.5 on first postoperative day. The average
      postoperative stay in hospital was 3.3 days (2-5 days). 2 cases experienced
      postoperative seroma but without adverse effect on the final outcome and no
      recurrences during the follow-up period of 1 to 6 months. Conclusions: TES
      procedure is safe, practical and minimally invasive requiring no specific device
      and highly reproducible. Besides there is no need for expensive anti-adhesion
      mesh and fixation tacker which make it more cost effective. TES is a good
      technique for the surgical treatment of midline ventral hernia.

PMID- 30293354
TI  - [MicroRNA-1249 regulates the apoptosis of myocardial cells in rats with chronic
      intermittent hypoxia by autophagy].
AB  - Objective: To investigate the regulation and possible mechanism of microRNA (miR)
      1249 on myocardial apoptosis in chronic intermittent hypoxia rats. Methods: A
      total of 16male SD rats aged 8 weeks were randomly divided into 2 groups by the
      random number table: normoxia control group and chronic intermittent hypoxia
      group (CIH) (n=8 each). The CIH group was exposed to intermittent hypoxia every
      day from 9: 00 to 17: 00 for 8 consecutive weeks, while the control group
      received the same frequency of pulse air. Hemodynamic values were measured via a
      cannula inserted into right common carotid artery. The expressions of miR-1249
      and microtubule-associated protein light chain 3 (LC3) mRNA were observed by real
      time PCR. The expressions of LC3 and Cleaved Caspase-3 were detected by Western
      bolt. TUNEL staining was performed to detect myocardial apoptosis. The rat
      cardiomyocyte cell H9C2 was divided into normoxia group, intermittent hypoxia
      (IH) group and miR-1249 inhibitor transfected and IH treatment group (inhibitor
      group). At the end of the experiment, the activation of LC3 protein in each group
      of cells was determined. Results: Compared with normoxia control group, left
      ventricle end diastolic pressure (LVEDP) increased [(4.6+/-0.4) vs (2.2+/-0.1)
      mmHg (1 mmHg=0.133 kPa)], left ventricular systolic pressure (LVSP) , maximal
      rate of pressure decline (-dp/dtmax), and maximal rate of pressure development (+
      dp/dtmax) decreased in CIH group [(92.7+/-4.1) vs (135.3+/-3.2) mmHg, (4 247+/
      108) vs (7 626+/-235) mmHg/s, and (3 168+/-105) vs (6 028+/-81) mmHg/s] (all
      P<0.001). The expression of miR-1249 and LC3 mRNA were significantly higher in
      CIH group than that in normoxia control group (all P<0.001), and a positive
      correlation was found between the expression of LC3 mRNA and miR-1249. The
      expression of LC3 and Cleaved Caspase-3 protein in myocardial tissue of CIH rats
      were significantly higher than that of the normoxia control group (all P<0.001).
      The proportion of myocardial cell apoptosis in CIH rats was significantly higher
      than that in the normoxia control group [(23.84+/-4.94)% vs (2.93+/-0.73)%]
      (P<0.001). The activation of LC3 in myocardial cells of inhibitor group was
      significantly lower than that of IH group, but higher than that in normoxia
      group. Conclusions: CIH could induce LC3 by raising the expression of miR-1249,
      and then induce the activation of apoptosis protein Caspase3. It ultimately
      induces myocardial apoptosis.

PMID- 30293355
TI  - [Development of burn medicine in the world and in China: a celebration of the
      60th anniversary of Chinese modern burn medicine].
AB  - In order to celebrate the 60th anniversary of Chinese modern burn medicine, the
      advancing history of burns in the world and in China were reviewed. Moreover, the
      rescuing abilities and levels of burns were compared between abroad and in China,
      clarifying the advantages and disadvantages of Chinese burn medicine. Finally,
      the challenges and development in the future of Chinese burn medicine were
      analyzed and addressed in this article.

PMID- 30293356
TI  - [Greeting the new era: reflection on the 60 years of Chinese burn medicine].
AB  - As an initial member of burn medicine in China, I am lucky to participate in the
      activity of writing paper for the journal to celebrate the 60th anniversary of
      the founding of burn medicine in China. It is a chance to introduce my clinical
      work, laboratory study, and teaching. I review the development of burn surgery to
      make some points in the transformation and development of burn surgery, some
      suggestions for better coordination between burn surgery and critical care
      medicine during emergency support for mass burn casualties. Furthermore, I wish
      that some of the differences in opinions and experience in burn care could be
      studied and conformed in order to form relatively uniform opinion which might
      benefit the successors.

PMID- 30293357
TI  - [Review of sixty years of Department of Burns of the 159th Hospital of PLA].
AB  - This paper describes the development of Department of Burns of the 159th Hospital
      of PLA in the past 60 years and shows their spirit of hard working and
      achievements of several generations.

PMID- 30293358
TI  - [Review of sixty years of burn discipline in Shanghai Ruijin Hospital].
AB  - Department of Burns and Plastic Surgery of Ruijin Hospital Affiliated to the
      Medical School of Shanghai Jiao Tong University is derived from the group of
      severe burn treatment in Surgical Department of Kuang-Ci Hospital in Shanghai in
      1958. In three score years, they created and developed distinctive technologies
      in treatment of massive deep burns, including early eschar excision on deep burn
      wound by stages and batches, taking the scalp as a donor site, wound covering
      with the large sheet of allo- or xeno-skin graft with small holes covered by
      small pieces of autoskin, the Ruijin formula for fluid resuscitation in early
      stage post burn and the " hibernation remedy" , which achieved actual effects in
      clinic, and they summed up academically the experiences of their clinical
      practice and researches. These technologies with other creations by Chinese burn
      surgeons have been named as " Chinese method" of burn treatment.

PMID- 30293359
TI  - [Retrospect of development and progress over the past 60 years and going further
      while carrying out practice].
AB  - This article briefly describes the establishment and development of Department of
      Burns and Reconstructive Surgery of Xiangya Hospital of Central South University.
      Over the past 60 years, our department has achieved great achievements in the
      treatment of burns by the combination of traditional Chinese medicine with
      western medicine, treatment of severe burns, and burn wounds repaired by flaps,
      and established Hunan burn rescue medical collaboration network. With the
      development of society and the change of disease spectrum, the future development
      direction of our department mainly focuses on treatment of severe burns, scar
      prevention, and treatment of acute and chronic wounds.

PMID- 30293360
TI  - [Brief review on four strategies for the development of burn discipline].
AB  - Discipline construction is the basis and grasp of hospital management, which is
      the cornerstone of brand, reputation and status at the same time. Strong
      discipline system, innovative research direction, and solid talent cultivation
      environment are the foundation and key to realize the sustainable development of
      hospitals, which have constituted the core competitiveness of the hospital. At
      present, the development of burn discipline faces many opportunities and
      challenges. This article discusses some thoughts on the construction and
      development of burn discipline, basing on the experience of construction and
      management of burn department in the author's unit.

PMID- 30293361
TI  - [Consensus on treatment of skin traumatic scars with photoelectric therapy and
      radio-frequency technology (2018 version)].
AB  - Traumatic scars not only affect local appearance and function, but also may be
      accompanied by pain, itching, and even psychological problems, which seriously
      affect the quality of patients' life. The prevention and treatment of scars are
      still quite challengeable for plastic and cosmetic surgery. Recently,
      photoelectric therapy and radio-frequency technology have brought breakthroughs
      in the clinical prevention and treatment of traumatic scars due to the
      developments of theory and practice on selective photothermolysis and fractional
      photothermolysis. Based on the analysis and summary of experience of treatment of
      traumatic scars with photoelectric therapy and radiofrequency technology in the
      past 5 years, the experts in the Department of Plastic and Reconstructive Surgery
      of Shanghai Ninth People's Hospital of Shanghai Jiao Tong University School of
      Medicine, together with expert consensus on treatment of scar using laser at home
      and abroad, organize the experts in the field of scar management from different
      regions in China to discuss and write the consensus on treatment of skin
      traumatic scars with photoelectric therapy and radio-frequency technology (2018
      version). This consensus is suitable for currently medical environment in China
      and aimed to provide standardized protocols for the treatment of skin traumatic
      scars in clinic.

PMID- 30293362
TI  - [Laser and related photoelectric therapies for scar worth expecting].
AB  - Effects of non-operative therapies for scar are very limited, and operative
      treatments are also often difficult to get satisfactory results. Safe, effective,
      simple, and feasible therapy for scar is urgently needed in clinic. Laser has
      been used for scar treatment for more than 30 years. There are many kinds of
      lasers, many of which have been reported to be used for scar treatment. Laser and
      related photoelectric therapies for scar have experienced long period of
      exploration, from the initial laser of continuous wavelength to the later pulsed
      laser, from ordinary spot laser in the early period to the present fractional
      laser. And there are intense pulsed light closely related to laser and non-light
      energy of micro-plasma radio-frequency technology. In recent years, with in-depth
      research of related theories, progress of technology and equipment, as well as
      accumulation of clinical experience, a great progress has been made in laser
      treatment for scar. In this article, related theories of photothermal interaction
      on skin tissue of laser, the present lasers and related photoelectric therapies
      often used for scar are introduced, and the existing problems and further
      development directions are also discussed.

PMID- 30293363
TI  - [Clinical comparative study of pulsed dye laser and ultra-pulsed fractional
      carbon dioxide laser in the treatment of hypertrophic scars after burns].
AB  - Objective: To compare the efficacy and safety of pulsed dye laser (PDL) and ultra
      pulsed fractional carbon dioxide laser (UFCL) in treating hypertrophic scars
      after burns. Methods: Two hundred and twenty one patients with hypertrophic scar
      after burns conforming to the study criteria were admitted to our unit from
      February 2015 to October 2017, and their data were retrospectively analyzed.
      Patients were divided into group PDL (n=122) and group UFCL (n=99) according to
      the treatment method. Patients in group PDL were treated with PDL once every 3-4
      weeks. Patients in group UFCL were treated with UFCL once every 6-12 weeks.
      Patients in both groups were treated until 12 months after having scar. Scars
      were scored by Vancouver Scar Scale (VSS) before and after treatment. Patients'
      pain was evaluated by Visual Analogue Scale (VAS) method before and after
      treatment. Blood flow in scar was monitored and recorded before treatment and in
      treatment months 6 and 12. Satisfaction degree of patients was recorded 3-6
      months after treatment, and the satisfaction rate was calculated. Adverse
      reactions including duration of erythema/purpura, VAS in treatment, and loss of
      working time were recorded. Data were processed with one-way analysis of
      variance, t test, and Chi-square test. Results: (1) VSS scores of patients in
      groups PDL and UFCL after treatment were significantly lower than those before
      treatment in the same group (t=11.34, 12.77, P<0.05). The decreasing VSS scores
      of patients after treatment in groups PDL and UFCL were (5.8+/-1.1) and (6.0+/
      1.4) points, respectively, and there was no statistically significant difference
      between the two groups (t=1.91, P>0.05). (2) VAS of patients in groups PDL and
      UFCL after treatment were significantly lower than those before treatment in the
      same group (t=7.12, 5.23, P<0.05). The decreasing VAS of patients after treatment
      in groups PDL and UFCL were (4.0+/-0.6) and (3.2+/-1.3) points, respectively, and
      there was no statistically significant difference between the two groups (t=1.93,
      P>0.05). (3) Scar blood flow of patients in group PDL in treatment months 6 had
      no obvious change compared with that before treatment (t=1.59, P>0.05), while
      that in treatment months 12 significantly decreased compared with that before
      treatment and that in treatment months 6 (t=3.17, 6.96, P<0.05). Scar blood flow
      of patients in group UFCL in treatment months 6 significantly increased compared
      with that before treatment (t=6.01, P<0.05), while that in treatment months 12
      significantly decreased compared with that in treatment months 6 (t=4.52,
      P<0.05), but had no obvious change compared with that before treatment (t=0.92,
      P>0.05). (4) The satisfaction degree of patients in group PDL was 80.3% (98/122),
      which in group UFCL was 76.8% (76/99), and there was no statistically significant
      difference between the two groups (chi(2)=0.97, P>0.05). (5) The duration of
      erythema/purpura of patients in group PDL was (5.2+/-0.7) d, significantly
      shorter than (6.1+/-0.5) d in group UFCL (t=2.49, P<0.05). The VAS of patients in
      group PDL during treatment was (1.9+/-0.9) points, significantly lower than
      (4.7+/-0.4) points in group UFCL (t=4.85, P<0.05). Loss of working time of
      patients in group UFCL was (9.17+/-0.72) d, which was significantly longer than
      (3.96+/-0.23) d in group PDL (t=3.17, P<0.05). Conclusions: PDL and UFCL have
      definite effects on hypertrophic scar, while PDL with light pain, minor wound,
      and fast recovery time, is safe and effective for treatment of early hypertrophic
      scar and worthy of clinical promotion and application, especially for children
      and patients with poor pain tolerance.

PMID- 30293364
TI  - [Clinical effects of a combination treatment with narrow-spectrum intense pulsed
      light and fractional carbon dioxide laser on hypertrophic scar pruritus].
AB  - Objective: To observe the effects of a combination treatment with narrow-spectrum
      intense pulsed light and fractional carbon dioxide laser on hypertrophic scar
      pruritus in clinic. Methods: A prospective randomized controlled study was
      conducted. A total of 90 patients with hypertrophic scars conforming to the
      inclusion criteria who were hospitalized in our ward from March to December 2017
      were divided into combination treatment group and control group according to the
      random number table, with 45 patients in each group. For scar pruritus, patients
      in control group were treated twice by narrow-spectrum intense pulsed light with
      a one-month interval, while patients in combination treatment group were firstly
      treated by narrow-spectrum intense pulsed light combined with fractional carbon
      dioxide laser once, and with narrow-spectrum intense pulsed light once one month
      later. Before and 3 months after treatment, scar pruritus was evaluated by the
      Visual Analogue Scale and the Four-item Itch Questionnaire, and the improvement
      of scar was assessed by photography. Three months after treatment, the treatment
      satisfaction of scar pruritus was self-rated by patients. Meanwhile, adverse
      effects were recorded during the procedures and follow-up periods. Data were
      processed with Chi-square test, paired t test, Wilcoxon rank-sum test, and
      Fisher's exact probability test. Results: Before treatment, there was no
      statistically significant difference in scar pruritus degree evaluated by the
      Visual Analogue Scale and score distribution of scar pruritus location, extent,
      frequency, and sleep effect of the Four-item Itch Questionnaire between patients
      of two groups (Z=-1.08, -0.91, -0.03, -0.69, -1.49, P>0.05). Three months after
      treatment, there was reducing degree of scar pruritus of patients evaluated by
      the Visual Analogue Scale in control group or combination treatment group
      compared with before treatment within the same group (Z=-1.98, -4.65, P<0.05 or
      P<0.01), while the latter was more obvious than the former (Z=-2.14, P<0.05).
      There were reducing scores of scar pruritus extent and frequency of patients in
      control group, along with location, extent, frequency, and sleep effect of
      patients in combination treatment group compared with those before treatment
      within the same group (Z=-2.33, -2.34, -3.53, -4.96, -3.32, -4.84, P<0.05 or
      P<0.01). However, scores of scar pruritus location and sleep effect of patients
      in control group were similar to those before treatment within the same group (Z=
      0.58, -1.34, P>0.05). The scores of scar pruritus location, extent, frequency,
      and sleep effect of patients were obviously lower in combination treatment group
      compared with control group (Z=-2.09, -2.69, -1.99, -2.23, P<0.05 or P<0.01). It
      was much better of scar improvement of patients in combination treatment group
      compared with control group (Z=-4.00, P<0.01). The percentages of treatment
      satisfaction of scar pruritus of patients with 0, 1%-25%, 26%-50%, 51%-75%, 76%
      100% were 0, 2.2% (1/45), 17.8% (8/45), 48.9% (22/45), and 31.1% (14/45)
      respectively in combination treatment group, which were obviously better than 0,
      11.1% (5/45), 53.3% (24/45), 28.9% (13/45), and 6.7% (3/45) in control group (Z=
      4.42, P<0.01). During the treatment and follow-up periods, the adverse effect
      ratio of patients in control group was 6.7% (3/45), similar to 2.2% (1/45) of
      combination treatment group (P>0.05). Conclusions: The combination of narrow
      spectrum intense pulsed light and fractional carbon dioxide laser can greatly
      reduce pruritus, improve effect of scar treatment, and bring higher patient
      satisfaction compared with narrow-spectrum intense pulsed light alone in treating
      hypertrophic scar pruritus. Clinical trial registration: Chinese Clinical Trial
      Registry, ChiCTR-ONH-17012350.

PMID- 30293365
TI  - [Clinical effects of sequential laser treatments on early stage hypertrophic burn
      scars].
AB  - Objective: To observe the clinical effects of sequential treatments of pulsed dye
      laser (PDL) and ablative fractional carbon dioxide laser on early stage
      hypertrophic burn scars. Methods: From January 2016 to December 2017, 221
      patients with 228 hypertrophic scars in all parts of body within 6 months post
      healing, conforming to the study criteria and treated in our department, were
      included in this prospective study. They were first treated by PDL, repeated at
      an interval of one month until the vascularity score of scar fell below 2 points,
      and then treated by ablative fractional carbon dioxide laser, repeated at an
      interval of 3 months. Their start time and numbers of treatment and follow-up
      time were recorded. Before the first treatment (hereinafter referred to as before
      treatment) and at the last follow-up (hereinafter referred to as after
      treatment), the vascularity, thickness, and pliability of scars were scored by a
      self-made scar rating scale. The scores of patients with the observation time
      between 6 to18 months post healing were compared among scars of patients grouped
      by age, body site of scar, starting time of treatment and numbers of treatment.
      The laser speckle contrast imaging technique was used to measure the blood flow
      value of scars. The itching symptom of the scars was evaluated by the Verbal
      Rating Scale. The satisfaction to the final effects of the doctors and patients
      was investigated and scored separately by Likert scale after treatment. The
      therapeutic or adverse reactions were recorded during the treatment. Data were
      processed with paired t test, Mann-Whitney U test, Wilcoxon signed rank sum test,
      Kruskal-Wallis H test, and Spearman rank correlation analysis. Results: (1) The
      patients were treated on (64+/-36) d post healing, by PDL for (2.5+/-1.3) times
      and by ablative fractional carbon dioxide laser for (2.2+/-1.2) times. The follow
      up time was (331+/-189) d. (2) The vascularity, thickness, pliability scores and
      total scores of scars were (1.4+/-0.9), (2.0+/-0.8), (1.7+/-0.8), and (5.0+/-2.1)
      points respectively after treatment, which were significantly lower than those
      before treatment [(4.1+/-0.7), (3.1+/-0.8), (3.0+/-0.9), and (10.2+/-2.0) points
      respectively, t=43.332, 24.968, 28.063, 46.394, P<0.01]. (3) Among the 123 scars
      from 120 patients with observation time between 6 to 18 months post healing,
      there were no statistically significant differences in the vascularity,
      thickness, pliability scores and total scores of scars among patients with
      different ages after treatment (chi(2)=4.339, 1.826, 1.375, 2.879, P>0.05). There
      was only significant difference in the pliability scores of scars among different
      body sites (chi(2)=13.530, P<0.05). There were statistically significant
      differences in the vascularity, thickness, pliability scores and total scores of
      scars with different starting time of treatment (chi(2)=30.725, 25.233, 25.119,
      35.798, P<0.01). There were significantly positive correlation between starting
      time of treatment and the vascularity, thickness, pliability scores and total
      scores of scars (r=0.492, 0.442, 0.446, 0.532, P<0.01). There were statistically
      significant differences in the vascularity, pliability scores and total scores of
      scars with different numbers of treatment (Z=4.883, 4.910, 5.049, P<0.05). There
      were significantly negative correlation between number of treatment and the
      vascularity, thickness, pliability scores and total scores of scars (r=-0.176, 
      0.131, -0.191, -0.201, P<0.05). (4) The blood flow values were determined in 18
      scars of 18 patients. The results showed that the blood flow values of scars
      after treatment were significantly decreased compared with those before treatment
      (t=7.230, P<0.01). (5) The pruritus scores of scars of patients after treatment
      were significantly decreased compared with those before treatment (Z=12.818,
      P<0.01). (6) There were significant differences between the satisfaction scores
      of doctors and the scores of patients after treatment (t=12.130, P<0.01). (7)
      After PDL treatment, there were some edema and purpura reactions for all the
      patients, and 11 (5.0%) patients had blisters. After ablative fractional carbon
      dioxide laser treatment, 4 (1.8%) patients had blisters, 5 (2.3%) patients
      suffered inflammatory reaction and erosion, and 9 (4.1%) patients suffered
      pigmentation. Conclusions: The scores of hypertrophic burn scars can be obviously
      improved by sequential treatments of PDL and ablative fractional carbon dioxide
      laser. The effects can be more obvious with the earlier starting time and more
      numbers of treatment. The laser treatments can also decrease the blood flow
      values and alleviate the pruritus of scars, with high satisfaction of both
      patients and doctors.

PMID- 30293366
TI  - [Occupational activity disorders of extremely severe mass burn patients in
      recovery period after injury: a cross-sectional survey].
AB  - Objective: To observe the distribution of occupational activity disorders of
      extremely severe mass burn patients in recovery period after injury. Methods:
      From December 2014 to December 2015, 65 extremely severe burn patients conforming
      to the inclusion criteria involved in August 2 Kunshan factory aluminum dust
      explosion accident were admitted to Kunshan Rehabilitation Hospital. They
      received comprehensive rehabilitation treatment after burns, including wearing
      pressure clothes, ultrasound treatment, semiconductor laser and red light
      irradiation, motor function training, and so on. Over 2 years after injury, a
      cross-sectional survey was conducted on the patients' occupational activity
      disorders. Modified Barthel index (MBI) was used to assess the degree of
      activities of daily living (ADL) disorder of patients and to grade the
      independent level of completing each item of MBI, and then the independent level
      of patients completing self-care MBI items (bathing, dressing, grooming, eating,
      going to the toilet, urine control, and stool control) was compared with that of
      mobility items (going up and down stairs, bed and chair transfer, and walking).
      The Canadian Occupational Performance Measure (COPM) was used to assess the
      distribution of occupational activity disorders of patients. The distribution of
      the five most serious occupational activity disorders was counted, then the
      frequency and probability of which with frequency greater than or equal to 16
      times were calculated. Data were processed with Pearson Chi-square test. Results:
      Over 2 years after injury, the MBI score of patients was (76+/-22) points, and
      the ADL of 83.08% (54/65) patients reached completely self-care or light ADL
      disorder level. The MBI items arranged according to the completing independent
      level of patients from high to low were urine control/stool control, walking, bed
      and chair transfer, going up and down stairs, going to the toilet, eating,
      grooming, dressing, and bathing. The independent level of patients completing
      self-care MBI items was lower than that of mobility items (chi(2)=62.298,
      P<0.001). Over 2 years after injury, the five most serious occupational activity
      disorders in COPM dimension were mainly concentrated in the self-care dimension,
      accounting for 55.38% (180/325), followed by 22.46% (73/325) of production
      activities and 22.15% (72/325) of recreational activities, and the centrally
      distributed item was the personal self-care item under self-care dimension,
      accounting for 42.46% (138/325). Over 2 years after injury, the five most serious
      occupational activity disorders with frequency greater than or equal to 16 times
      were dressing and undressing, bathing, perineal cleaning, wearing pressure
      clothes, caring for children, visiting relatives and friends, 31, 25, 16, 17, 18,
      and 22 times respectively, with a probability of 47.69%, 38.46%, 24.62%, 26.15%,
      27.69%, and 33.85% respectively. Conclusions: Over 2 years after injury, most of
      the patients with extremely severe burns caused by the aluminum dust explosion
      were completely or basically self-care in their daily life. The disorder of self
      care ADL was more serious than that of mobility, and the disorder of individual
      self-care activity was still the most serious occupational activity disorder of
      patients in this stage. Clinical trial registration: Chinese clinical trial
      registry, ChiCTR-OOC-16009188.

PMID- 30293367
TI  - [Influences of hydrogen-rich saline on acute kidney injury in severely burned
      rats and mechanism].
AB  - Objective: To explore the influences of hydrogen-rich saline on acute kidney
      injury in severely burned rats and to analyze the related mechanism. Methods:
      Fifty-six Sprague Dawley rats were divided into sham injury group (n=8), burn
      group (n=24), and hydrogen-rich saline group (n=24) according to the random
      number table. Rats in sham injury group were treated by 20 C water bath on the
      back for 15 s to simulate injury, and rats in burn group and hydrogen-rich saline
      group were inflicted with 30% total body surface area (TBSA) full-thickness scald
      (hereinafter referred to as burns) by 100 C water bath on the back for 15 s.
      Immediately after injury, hydrogen-rich saline at the dose of 10 mL/kg were
      intraperitoneally injected to the rats in hydrogen-rich saline group at one time,
      while normal saline with the same dose were intraperitoneally injected to the
      rats in sham injury group and burn group. At post injury hour (PIH) 6, rats in
      the 3 groups were intraperitoneally injected with 4 mL.kg(-1).%TBSA(-1) lactated
      Ringer's solution for resuscitation. Eight rats from sham injury group at PIH 72
      and eight rats from burn group and hydrogen-rich saline group at PIH 6, 24, and
      72 were sacrificed respectively after their blood samples from abdominal aorta
      were collected. Then their kidney tissue was harvested for histopathological
      observation and renal tubular injury scoring by hematoxylin and eosin staining,
      serum creatinine and blood urea nitrogen were detected by the clinical blood
      biochemical analyzer, expression distribution and mRNA expressions of tumor
      necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in
      renal tissue were evaluated by immunohistochemical staining and real time
      fluorescent quantitive reverse transcription polymerase chain reaction
      respectively, and protein expression of high mobility group protein 1 (HMGB1) was
      detected by Western blotting. Data were processed with Kruskal-Wallis H test,
      Dunn test, one-way analysis of variance, Bonferroni test. Results: (1) The renal
      tubular structure of rats in sham injury group at PIH 72 was complete with no
      inflammatory cell infiltration and no cellular degeneration or necrosis. Since
      PIH 6, the changes such as vacuolation and shape change of cells and aggregation
      of broken protein in renal tubules were observed in rats of burn group, and all
      these changes deteriorated with time. The renal injury of rats in hydrogen-rich
      saline group at different post injury time points were relieved compared with
      those of rats in burn group at the corresponding time points. The renal tubular
      injury scores of rats in burn group and hydrogen-rich saline group at PIH 6, 24,
      and 72 were significantly higher than the score in sham injury group at PIH 72
      (P<0.05). The renal tubular injury scores of rats in hydrogen-rich saline group
      were significantly lower than those in burn group at PIH 6, 24, and 72 (P<0.05).
      (2) Except for those in hydrogen-rich saline group at PIH 6 and 72 (P>0.05), the
      levels of serum creatinine of rats in burn group at all the time points and
      hydrogen-rich saline group at the other time points were significantly higher
      than the level of serum creatinine of rats in sham injury group at PIH 72
      (P<0.01). The levels of blood urea nitrogen of rats in burn group and hydrogen
      rich saline group at PIH 6, 24, and 72 were significantly higher than the level
      of blood urea nitrogen of rats in sham injury group at PIH 72 (P<0.01). The
      levels of serum creatinine and blood urea nitrogen of rats in hydrogen-rich
      saline group at PIH 6, 24, and 72 were significantly lower than those in burn
      group at the corresponding time points (P<0.05). (3) There were certain degree of
      positive expressions of TNF-alpha, IL-1beta, and IL-6 in renal tissue of rats in
      sham injury group at PIH 72, which were mainly observed in the cytoplasm of renal
      tubular epithelium cell. The expressions of above-mentioned inflammatory
      cytokines in renal tissue of rats in burn group at PIH 6, 24, and 72 were higher
      than those in sham injury group. The expressions of above-mentioned inflammatory
      cytokines in renal tissue of rats in hydrogen-rich saline group at all the time
      points were less than those in burn group at the corresponding time points. (4)
      Compared with those in sham injury group at PIH 72, the mRNA expression levels of
      TNF-alpha, IL-1beta, and IL-6 of rats in burn group at PIH 6, 24, and 72 were
      significantly increased (P<0.01). The mRNA expression levels of TNF-alpha were
      significantly increased in hydrogen-rich saline group at PIH 6 and 24 (P<0.05 or
      P<0.01), and the mRNA expression level of IL-6 was significantly increased in
      hydrogen-rich saline group at PIH 6 (P<0.01). Compared with those at the
      corresponding time points in burn group, except for the mRNA expression level of
      TNF-alpha in hydrogen-rich saline group at PIH 6 showed no significant
      differences (P>0.05), and the mRNA expression levels of TNF-alpha, IL-1beta, and
      IL-6 at the other time points in hydrogen-rich saline group were significantly
      decreased (P<0.05). (5) Compared with 0.39+/-0.03 in sham injury group at PIH 72,
      the protein expression of HMGB1 of rats in burn group at PIH 6, 24, and 72
      (1.19+/-0.07, 1.00+/-0.06, 0.80+/-0.05) were significantly increased (P<0.05),
      while the protein expression of HMGB1 of rats in hydrogen-rich saline group at
      PIH 6, 24, and 72 (0.35+/-0.08, 0.47+/-0.06, 0.42+/-0.06) showed no significant
      differences (P>0.05). Compared with those in burn group, the protein expressions
      of HMGB1 of rats in hydrogen-rich saline group at PIH 6, 24, and 72 were
      significantly decreased (P<0.05). Conclusions: Hydrogen-rich saline can alleviate
      the acute kidney injury in severely burned rats through regulating the release of
      inflammatory cytokines in renal tissue.

PMID- 30293368
TI  - [Clinical application of platelet-rich fibrin in chronic wounds combined with
      subcutaneous stalking sinus].
AB  - Objective: To investigate the clinical effect of platelet-rich fibrin (PRF) in
      the treatment of chronic wounds combined with subcutaneous stalking sinus caused
      by various kinds of reasons. Methods: The clinical data of 72 patients with
      chronic wounds and combined with subcutaneous stalking sinus caused by various
      kinds of reasons admitted to our unit from June 2015 to February 2017, conforming
      to the study criteria, were collected and retrospectively analyzed. Patients were
      divided into group PRF (n=39) and routine dressing change (RDC) group (n=33)
      according to their treatment. The subcutaneous stalking sinuses of patients in
      group PRF were filled with PRF 1 or 2 times after debridement, while the surface
      of wound was covered by vaseline gauze and aseptic dressing, and dressing change
      was performed once per 2-3 days. The wounds of patients in group RDC were filled
      with iodine gauze after debridement of wounds and wrapped up with conventional
      aseptic dressing, and dressing change was performed once per 0.5-2.0 days. The
      times of operation, the times of dressing change, the time for negative
      conversing of bacteria culture in the secretion of wound, the time of
      subcutaneous stalking sinus closure, and the complete healing time of wounds of
      patients in two groups were recorded. Data were processed with Chi-square test
      and independent sample t test. Results: The operation times of patients in two
      groups were close (t=0.565, P>0.05). The dressing changes of patients in group
      PRF were (6.4+/-2.1) times, significantly less than (19.2+/-6.2) times in group
      RDC, t=12.107, P<0.01. The time for negative-conversing of bacteria culture in
      the secretion of wound of patients in group PRF was (15+/-5) d, significantly
      shorter than (25+/-9) d in group RDC, t=6.087, P<0.01. The time of subcutaneous
      stalking sinus closure of patients in group PRF was (12+/-5) d, significantly
      shorter than (24+/-8) d in group RDC, t=7.315, P<0.01. The complete healing time
      of wounds of patients in group PRF was (23+/-7) d, significantly shorter than
      (35+/-10) d in group RDC, t=5.924, P<0.01. All the chronic wounds of patients in
      two groups were completely healed, and there were no break or new sinus formed
      during the follow-up of 4-12 months after discharge. Conclusions: The application
      of PRF in the treatment of chronic wounds combined with subcutaneous stalking
      sinus caused by various reasons can bring about rapidly healing of wounds,
      definite effect, and convenient operation, thus is worth promoting and applying
      in clinic.

PMID- 30293369
TI  - [Mutations in A((8)) and A((9)) loci of exon 8 of retinoblastoma protein
      interacting zinc finger gene of keloid patients].
AB  - Objective: To study the situation of the mutations in the A((8)) and A((9)) loci
      of exon 8 of retinoblastoma protein-interacting zinc finger gene (RIZ) of keloid
      patients. Methods: From January 2003 to December 2007, 19 outpatient and
      hospitalized keloid patients of our hospital were conforming to the inclusion
      criteria. Both 3-5 g keloid tissue and 3 mL peripheral venous blood were
      collected from each patient to extract their genomic DNA, and the concentration
      was determined. The A((8)) and A((9)) loci fragments of exon 8 of RIZ were
      amplified by polymerase chain reaction (PCR). The length of product was detected
      by agarose gel electrophoresis, and DNA sequencing was performed after column
      chromatography. The mutations of A((8)) and A((9)) loci fragments were searched,
      and the types of mutations were determined. The consistency of genetic mutations
      of the keloid tissue and peripheral venous blood were compared. Data were
      processed with McNemar test. Results: The DNA concentrations of the extracted
      keloid tissue and peripheral venous blood were 0.54 and 0.37 MUg/MUL,
      respectively, which were above 0.10 MUg/MUL. The lengths of PCR products of
      A((8)) locus fragment DNA of exon 8 of RIZ from keloid tissue and peripheral
      venous blood were 235 and 238 bp, respectively, and those of A((9)) locus were
      242 and 244 bp, respectively, which were basically the same as the designed DNA
      fragments. PCR products purity of A((8)) locus fragment DNA of exon 8 of RIZ from
      keloid tissue and peripheral venous blood were 1.81 and 1.75, respectively, and
      those of A((9)) locus were 1.82 and 1.78, respectively, which were above 1.50.
      Mutations in the A((8)) locus of exon 8 of RIZ were observed in keloid tissue of
      18 patients, totally 6 gene mutations, including 4 point mutations and 2
      frameshift mutations. Mutations in the A((9)) locus of exon 8 of RIZ were
      observed in keloid tissue of 9 patients, totally 9 gene mutations, including 7
      point mutations and 2 frameshift mutations. No patient had a mutation in the
      A((8)) or A((9)) locus of exon 8 of RIZ in peripheral venous blood. Compared with
      those of peripheral venous blood, the mutations in the A((8)) and A((9)) loci of
      exon 8 of RIZ in keloid tissue of patients were statistically significant
      (chi(2)=16.06, 7.11, P<0.05). Conclusions: Point mutations and frameshift
      mutations occur in the A((8)) and A((9)) loci of exon 8 of RIZ in keloids of
      patients, which may be associated with the occurrence of keloids.

PMID- 30293370
TI  - [Influences of comprehensive nursing intervention on the caregivers of severely
      burned children].
AB  - Objective: To explore the influences of comprehensive nursing intervention on the
      caregivers of severely burned children. Methods: Eighty severely burned children,
      admitted to our department from November 2016 to November 2017 and conforming to
      the study criteria, were included in this study. They were divided into
      comprehensive group and control group according to the random number table, with
      40 children in each group. One caregiver for each child was included in the same
      group. Children and caregivers in control group had routine nursing care while
      children and caregivers in comprehensive group had comprehensive nursing care on
      the base of routine nursing care, including comprehensive psychological nursing
      of children and caregivers, guidance of rehabilitation for caregivers throughout
      the entire recovery process, individualized propaganda and education for
      caregivers on account of disease of children, perfecting social support system,
      sustained attention of children during follow-up. Anxiety self-rating scale and
      social support rating scale were used to assess the levels of anxiety and social
      support of caregivers of children in the two groups at the time of admission
      (before intervention) and the second month after discharge (the third time follow
      up, after intervention). On the day of discharge, the nursing service
      satisfaction questionnaire of our department was used to evaluate the nursing
      service satisfaction of caregivers of children. Data were processed with chi
      square test and independent sample t test. Results: (1) Before intervention, the
      anxiety and social support scores of caregivers of children in control group were
      respectively (64.5+/-3.8) and (40.4+/-2.5) points, similar to (63.5+/-4.9) and
      (40.5+/-2.6) points in comprehensive group (t=0.988, 0.177, P>0.05). After
      intervention, the anxiety score [(47.2+/-1.9) points] of caregivers of children
      in comprehensive group was significantly lower than that of control group
      [(57.6+/-4.3) points, t=13.917, P<0.01], and the social support score [(45.3+/
      1.9) points] was significantly higher than (35.9+/-2.1) points in control group
      (t=-21.282, P<0.01). After intervention, scores of objective support, subjective
      support, and social support utilization in the social support evaluation rating
      of caregivers of children in comprehensive group were significantly higher than
      those in control group (t=12.678, -11.079, -10.031, P<0.01). (2) At the time of
      discharge, scores of clinical care, propaganda and education content and form in
      the nursing service satisfaction questionnaire of caregivers of children in
      comprehensive group were significantly higher than those of control group (t=
      14.757, -15.627, -33.221, P<0.01). Conclusions: Comprehensive nursing
      intervention method can effectively reduce the anxiety of the caregivers of
      severely burned children, help them to make better use of social support system,
      and improve the satisfaction of caregivers in nursing services.

PMID- 30293372
TI  - [The blood pressure between 130-139/80-89 mmHg should be seriously considered].

PMID- 30293371
TI  - [Advances in the research of influence of diabetes in biological function of
      adipose-derived stem cells].
AB  - Adipose-derived stem cells (ADSCs) are adult mesenchymal stem cells in adipose
      tissue with self-renewal and multi-directional differentiation potential. The
      application of ADSCs in the treatment of wounds has achieved good results.
      Because of its extensive sources, high content in vivo, low immunogenicity,
      slight injury to body when obtained, the clinical application prospect of ADSCs
      is promising. The reasons why diabetic wound is difficult to heal may be closely
      related to the increase of advanced glycation end products, long-term chronic
      inflammatory response, and peripheral neurologic dysfunction. The abnormal
      internal environment of diabetic patients can affect the biological function of
      ADSCs, which further affects wound healing. This article reviews the general
      feature, differentiation, proliferation, migration, secretion, and pro-angiogenic
      function of diabetic ADSCs.

PMID- 30293373
TI  - [Is hyperhomocysteinaemia an independent risk factor for cardiovascular and
      cerebrovascular diseases?]

PMID- 30293374
TI  - [Guideline on the diagnosis and treatment of stable coronary artery disease].

PMID- 30293375
TI  - [Association between long-term blood pressure change and the incidence of
      cardiovascular diseases: a population-based cohort study].
AB  - Objective: To explore the association between long-term changes in blood pressure
      (BP) levels and the incidence of cardiovascular diseases (CVD). Methods: A total
      of 5 752 participants, who participated baseline examination in 1992-1993 and re
      examination in 2007, were followed up till December 31, 2013 according to the
      study protocol of the Chinese Multi-provincial Cohort Study. Participants were
      stratified by baseline BP and re-examination BP and cross-combined into 9
      subgroups. The 20-year incidence of acute cardiovascular events, acute coronary
      heart disease (CHD) and acute stroke events were analyzed and association between
      disease incidence and 15-year changes in BP were determined using the competing
      risk regression model. Results: (1) There were 523 CVD events (170 CHD, 373
      stroke) during the 20 years follow up. The number of participants with baseline
      systolic blood pressure (SBP)/diastolic blood pressure (DBP) of <130/80 mmHg (1
      mmHg=0.133 kPa), 130-139/80-89 mmHg, and hypertension were 2 892 (50.3%), 1 328
      (23.1%) and 1 532 (26.6%), respectively. (2) Among participants with baseline SBP
      of 130-139 mmHg or DBP of 80-89 mmHg, 870 (65.5%) progressed to hypertension and
      279 (21.0%) maintained at the same stratum over a 15-year follow up period. (3)
      After adjustment for age, sex, body mass index, smoking status, diabetes, total
      cholesterol, and high-density lipoprotein cholesterol at baseline, participants
      maintained SBP/DBP at 130-139/80-89 mmHg had a higher risk of developing acute
      cardiovascular events, CHD and stroke with the hazard ratios (HR) and 95%
      confidence interval (95%CI) of 2.04 (1.16, 3.57), 3.29 (1.30, 8.35) and 1.63
      (0.80, 3.33), compared with those who maintained their SBP < 130 mmHg and DBP <80
      mmHg. Participants whose BP increased from 130-139/80-89 mmHg to hypertension
      over the follow up period had 2.81-fold (1.84, 4.29), 3.17-fold (1.43, 7.03) and
      2.71-fold (1.65, 4.44) higher risk for the incidence of acute cardiovascular
      events, CHD, and stroke, respectively, compared with participants who maintained
      their SBP <130 mmHg and DBP <80 mmHg. Conclusions: Participants with SBP/DBP of
      130-139/80-89 mmHg have a high long-term risk for progression to hypertension.
      Sustained exposure to SBP/DBP of 130-139/80-89 mmHg or higher increases the risk
      of CVD incidence, and our results highlight the importance of early prevention
      for participants with this BP stratum.

PMID- 30293376
TI  - [Mediating effect of hemoglobin and hematocrit on the association between alcohol
      consumption and blood pressure among middle-aged and elderly male residents in
      Guangzhou].
AB  - Objective: To explore the mediating effect of hemoglobin (Hb) and hematocrit
      (HCT) on the association between alcohol consumption and blood pressure, and
      provide evidence for the prevention and control of alcohol-attributed
      hypertension. Methods: 1 091 male (age >50 years old) participants with drinking
      habit were selected from the Guangzhou biobank cohort study (GBCS). Mediation
      analysis was used to evaluate the mediating effect of Hb and HCT on the
      association of alcohol consumption (unit/day) with systolic blood pressure (SBP),
      diastolic blood pressure(DBP), pulse pressure(PP) and mean arterial pressure
      (MAP). Results: After adjusting for age, body mass index, education level,
      personal annual income, smoking, occupation and physical activity, the
      associations of alcohol consumption with SBP, DBP, PP and MAP were partly
      mediated by Hb, the proportion of mediating effect was 11.8% (95%CI 4.8%-24.7%),
      15.3% (95%CI 6.5%-32.0%), 8.4% (95%CI 2.2%-22.5%) and 13.5% (95%CI 5.9%-27.5%),
      respectively. The associations of alcohol consumption with SBP, DBP, and MAP were
      also partly mediated by HCT, the proportion of mediating effect was 6.3% (95%CI
      1.0%-16.0%), 8.7% (95%CI 1.4%-21.4%), and 7.5% (95%CI 1.0%-18.6%), respectively.
      Conclusion: There is a significant mediating effect of Hb and HCT on the
      association between alcohol consumption and blood pressure. Besides efforts on
      alcohol control, the potential effects of alcohol-induced increase on Hb and HCT,
      which might also increase the blood pressure, need to be considered to achieve
      optimal monitoring and prevention of alcohol-related hypertension.

PMID- 30293377
TI  - [Analysis of structural features of gut microbiota in two-kidney-one-clip
      hypertensive rats based on high-throughput sequencing technology].
AB  - Objective: To characterize the gut microbial community structure of two-kidney
      one-clip (2K1C) hypertensive rats, provide new evidences for prevention and
      treatment of hypertension. Methods: Adult male SD rats were divided into 2K1C
      hypertensive model group and sham operation group (n=8 each). Blood pressure was
      recorded by tail-cuff technique weekly for 4 weeks. Then, the total fecal DNA of
      rats in 2K1C model group and sham operation group were extracted. The structure
      and principal components of intestinal flora in 2K1C model rats and sham operated
      rats were analyzed using Hiseq3000 sequencing platform. Additionally, real time
      fluorescent quantitative polymerase chain reaction technology was used to detect
      the content of predominant bacteria, including Escherichia, Bifidobacterium,
      Lactobacillus and Bacteroides. Results: Compared with sham operation group,
      significant reduction in the relative abundance of Firmicutes (31.72 (30.06,
      32.18) vs. 40.99 (38.78, 44.41), U=0.00, P<0.05) and increase in Bacteroidetes
      (48.13(41.16,50.25) vs. 27.81(25.84,31.38),U=0.00, P<0.05) were observed in the
      fecal samples from model group. The relative abundance of Escherichia coli
      (0.08(0.07,0.11) vs. 0.07(0.06,0.08),U=12.50, P<0.05) was increased and the short
      chain fatty acid producing strains such as Coprococcus, Roseburia, Blautia,
      Clostridium and Bacteroides was reduced in 2K1C model group than in sham
      operation group (all P<0.05). Moreover, the relative abundance of Prevotella
      (Bacteroidetes) was also significantly higher in 2K1C model group than in sham
      operation group (18.14(17.78,18.75) vs.1.83(1.50,5.19), U=0.00, P<0.05).
      Moreover, the relative abundance of Ruminococcus (Firmicutes) was significant
      higher in 2K1C model group than in sham operation group (7.73(6.04,9.34) vs.
      3.68(2.46,4.67),U=0.00, P<0.05). Principal coordinate analysis showed that there
      was significant difference in the gut microbial community structure between 2K1C
      model group and sham operation group. Conclusion: There are significant changes
      in the gut microbial community structure in 2K1C model group as compared to sham
      operation group, indicating renovascular hypertension might affect gut microbial
      community structure in this rat model.

PMID- 30293378
TI  - [Association between platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte
      ratio with disease activity in Takayasu arteritis patients].
AB  - Objective: To explore the relation between platelet-to-lymphocyte ratio (PLR) or
      neutrophil-to-lymphocyte ratio (NLR) with disease activity in Takayasu arteritis
      (TA) patients. Methods: Present retrospective study involved 289 patients with
      TA, who were hospitalized in our department between January 2010 and October
      2017, and 280 age and gender matched healthy controls,who underwent thealth
      examination in our health examination center during the same period (control
      group). TA patients were further divided into active and inactive groups (180 and
      109 cases respectively) according to Kerr scores. The clinical data were compared
      between groups. Pearson correlation analysis was used to evaluate the
      relationship between PLR or NLR and disease activity (Kerr score or C-reactive
      protein or erythrocyte sedimentation rate). Receiver operating characteristic
      (ROC) curve was employed to judge the cut-off value of disease activity for TA
      patients. Results: PLR and NLR were significantly higher in TA group than in
      control group(137.33 (97.38, 193.37) vs. 120.55 (96.86, 144.60) and 2.38 (1.76,
      3.57) vs. 1.66 (1.35, 2.08) , respectively, all P<0.001). PLR and NLR were
      significantly higher in active TA group than in inactive TA group (163.43
      (123.64, 224.15) vs. 110.53 (84.22, 147.24) and 2.59 (1.96, 3.94) vs. 1.95 (1.53,
      2.86) respectively, all P<0.001). PLR and NLR of active group were significantly
      decreased after 6 months treatment (164.05 (123.29, 226.29) vs. 104.67 (77.22,
      138.43) and 2.58 (1.96, 3.91) vs. 2.15 (1.67, 2.60) respectively, all P<0.001).
      PLR was positively correlated with Kerr score (r=0.439, P<0.001), C-reactive
      protein (r=0.328, P<0.001) and erythrocyte sedimentation rate (r=0.410, P<0.001).
      NLR also exhibited a positive relationship with Kerr score (r=0.235, P<0.001), C
      reactive protein (r=0.169, P=0.005) and erythrocyte sedimentation rate (r=0.123,
      P=0.037). A PLR level of 176.709 was shown to be the best predictive cut-off
      value for TA disease activity (sensitivity 44.6%, specificity 93.0%, and area
      under the curve=0.766).A NLR level of 2.128 was shown to be the best predictive
      cut-off value for TA disease activity (sensitivity 70.9%, specificity 47.7%, and
      area under the curve=0.691). Conclusion: PLR and NLR are useful markers for
      predicting disease activity of TA patients.

PMID- 30293379
TI  - [Paclitaxel enhances the protective effect of myocardial ischemia preconditioning
      on ischemia/reperfusion injury in aged rat].
AB  - Objective: To investigate if paclitaxel can enhance the protective effect of
      myocardial ischemia preconditioning on ischemia/reperfusion injury in aged ratand
      explore related mechanism. Methods: Primary cardiomyocytes of Sprague-Dawley rats
      were isolated by trypsin and divided into 5 groups(n=6 each): control group,
      hypoxia injury group, hypoxia preconditioning group, paclitaxel group,and
      paclitaxel+hypoxia preconditioning group. The structure of microtubules and the
      expression of hypoxia-inducible factor-1alpha(HIF-1alpha) were analyzed by
      immunofluorescence staining. The Langendorff isolated heart perfusion model was
      applied in 4 groups: hypoxia reperfusion injury group, hypoxia preconditioning
      group, paclitaxel group, and paclitaxel+hypoxia preconditioning group. Each group
      was further divided into elderly subgroup and adult subgroup (n=6 each). Left
      ventricular developed pressure and maximum rate of rise in left ventricular
      pressure were analyzed. Results: (1) Primary cardiomyocyte experiments showed
      that the myocardial tubular microtubule structure in control group was intact and
      evenly stained; most of the microtubules in the hypoxia-injured group were absent
      and the tubular tissue was broken; the hypoxia-induced damage on microtubule
      structure was smaller in the hypoxic preconditioning group compared with the
      hypoxic injury group (microtubule staining was not uniform, and the lattice
      structure was broken, but not that obvious as in the hypoxia group); the tubular
      structure of the microtubules of the paclitaxel group was basically complete, and
      the staining was basically uniform.The integrity of tubular structure was
      maintained to some extent, similar to a normal microtubule structure in
      paclitaxel+hypoxia preconditioning group. The expression of HIF-1alpha in the
      cytoplasm and nucleus was very low in the control group, which was evidenced in
      both cytoplasm and nucleus in the hypoxic injury group.The expression was further
      increased in hypoxic preconditioning group, significant nuclear HIF-1 expression
      was found in the paclitaxel group, the expression was aggregated in the nucleus
      in the Paclitaxel+ hypoxia preconditioning group. (2)In Langendorff isolated
      heart perfusion model, left ventricular developed pressure was similar between
      the elderly subgroup and the adult subgroup at the end of the infusion,after
      precondition, 5 minutes of reperfusion, 30 minutes of reperfusion, and 60 minutes
      of reperfusion in the hypoxic injury group (all P> 0.05).In the hypoxic injury
      group, both the elderly subgroup and the adult subgroup had lower left
      ventricular developed pressure at 30 minutes of reperfusion when compared with
      the end of the infusion((15.63+/-4.88) mmHg (1 mmHg=0.133 kPa) vs. (95.63+/
      22.14)mmHg and (17.31+/-2.75)mmHg vs. (91.00+/-9.58)mmHg, respectively,all
      P<0.05). In the hypoxic preconditioning group, the adult subgroup had higher left
      ventricular developed pressure at 5 and 30 minutes of reperfusion when compared
      with the elderly subgroup((7.13+/-1.02) mmHg vs. (3.75+/-1.06)mmHg and (43.94+/
      3.21)mmHg vs.(16.31+/-1.54)mmHg, respectively,all P<0.01). In the paclitaxel
      group, the adult subgroup had higher left ventricular developed pressure at 30
      and 60 minutes of reperfusion when compared with the elderly subgroup((44.31+/
      7.59)mmHg vs. (5.44+/-1.21)mmHg, (51.56+/-6.03)mmHg vs. (22.19+/-5.14)mmHg,
      respectively, all P<0.01). In the paclitaxel+hypoxia preconditioning group, both
      the elderly subgroup and the adult subgroup had lower left ventricular developed
      pressure at 30 minutes of reperfusion when compared with the end of the
      infusion((18.63+/-4.30)mmHg vs. (99.94+/-8.23) mmHg, P<0.01; (49.69+/-5.34)mmHg
      vs. (95.31+/-5.26)mmHg, P<0.05). Meanwhile, the adult subgroup had higher left
      ventricular developed pressure at 30 minutes of reperfusion when compared with
      the elderly subgroup((49.69+/-5.34)mmHg vs. (18.63+/-4.33)mmHg, P<0.01).The adult
      subgroup had higher change rate of maximum rate of rise in left ventricular
      pressure at 60 minutes of reperfusion when compared with the elderly subgroup in
      hypoxia preconditioning group, paclitaxel group, and paclitaxel combined hypoxia
      preconditioning group((62.83+/-3.92)% vs. (33.33+/-3.20)%, (44.17+/-2.32)% vs.
      (36.67+/-2.88)%, (72.50+/-2.66)% vs. (53.17+/-2.56)%, respectively,all P<0.01).
      Conclusion: Paclitaxel can enhance the myocardial protective effect of myocardial
      ischemia preconditioning through stabilizing microtubules of cardiomyocytes and
      promoting HIF-1alpha localization in the nucleus.

PMID- 30293381
TI  - [A case of acute myocardial infarction with downsloping ST segment depression and
      tall peaked T wave].

PMID- 30293380
TI  - [Analysis on the gender-specific risk factors of new-onset cerebral hemorrhage].
AB  - Objective: To explore the gender-specific risk factors of new-onset cerebral
      hemorrhage. Methods: In this prospective cohort study,a total of 98 961
      participants((51.1+/-12.6)years old), who underwent the 2006 to 2007 physical
      examination and met the inclusion criteria, were enrolled from the Kailuanstudy
      cohort. There were 78 908 (79.7%) male,and 20 053 (20.3%) female.The incidence of
      cerebral hemorrhage was observed once per year until December 31, 2016.The
      difference on the incidence of cerebral hemorrhage between male and female was
      compared. Multivariate Cox regression analysis was applied to analyze therisk
      factors of cerebral hemorrhage events among different genders. Results: The
      participants were followed up for(10.00+/-0.73) years,and 860 cerebral hemorrhage
      events were recorded during follow up. The incidence of cerebral hemorrhage in
      the population was 86.90/10 million person years (standardized incidence rate of
      47.85/10 million person years). The incidence of cerebral hemorrhage was
      significantly higher in male (49.61/10 million person years) than in female
      (34.07/10 million person years, P<0.05). Multivariate Cox regression analysis
      showed that 45-59 years old, >= 60 years old, diabetes,and waist-hip ratio were
      more strongly related to new-onset of cerebral hemorrhage events in female than
      in male, and the hazard ratios(95%CI) were 2.33 (1.23-4.43) ,2.71 (1.30-5.66)
      ,2.16 (1.24-3.74) and 8.79 (1.42-54.32) in female versus 1.55 (1.21-1.97) ,2.16
      (1.68-2.78) ,1.19 (0.93-1.53) and 3.21 (1.09-9.41) in male, respectively. The
      risk of male cerebral hemorrhage increased by 29% (HR=1.29, 95%CI 1.19-1.40) in
      male and 24% (HR=1.24, 95%CI 1.20-1.28) in female,when the systolic blood
      pressure increased 10 mmHg (1 mmHg=0.133 kPa). Conclusions: The incidence of
      cerebral hemorrhage is higher in male than in female in this cohort.The
      association between systolic blood pressure and cerebral hemorrhage is stronger
      in male than that in female.The associations between age, waist-hip ratio,
      diabetes and cerebral hemorrhage are stronger in female than in male. Trial
      Registration: Chinese Clinical Trail Registry, ChiCTR-TNC-11001489.

PMID- 30293382
TI  - [A case of congenital pulmonary vein malformations undergoing interventional
      treatment].

PMID- 30293383
TI  - [Update on the role of innate immune signaling molecules on myocardial remodeling
      in systemic hypertension].

PMID- 30293384
TI  - [Mechanisms and pathophysiological significance of endothelial injury on
      superficial erosion of atherosclerotic plaque].

PMID- 30293385
TI  - [Research update on the AGE/RAGE signaling mediated vascular calcification in
      diabetes].

PMID- 30293386
TI  - [Research progression on triage of human papillomavirus positive women].
AB  - Persistently high risk human papillomavirus (HPV) infection is one of the
      indispensable factors of cervical cancer, which is the secondly most common
      cancer of women in developing countries. Nowadays HPV DNA detection has been more
      frequently used in cervical cancer initial screening. However, the specificity
      and sensitivity of HPV DNA detection are low and the triage of HPV positive women
      is necessary to identify the authentically high-risk population, and avoid the
      waste of health care resource and excessive treatment. There are different
      advantages and disadvantages in triage methods including the cytology, HPV DNA
      genotype, HPV mRNA detection and biological markers such as p16/Ki-67,
      respectively. Here we briefly describe and evaluate each triage method.

PMID- 30293387
TI  - [Incidence and mortality of bladder cancer in China, 2014].
AB  - Objective: To estimate the incidence and mortality of bladder cancer in China
      based on the cancer registration data in 2014, collected by the National Central
      Cancer Registry (NCCR). Methods: There were 449 cancer registries submitted
      bladder cancer new cases and deaths occurred in 2014 to NCCR. After evaluating
      the data quality, 339 registries' data were finally accepted for analysis.
      According to the national population data of 2014, the nationwide incidence and
      mortality of bladder cancer were estimated by stratification in the area (urban
      or rural), gender, and age. Chinese population census in 2000 and Segi's
      population were used for age-standardized incidence/mortality rates. Results: All
      339 cancer registries covered a total of 288 243 347 populations (144 061 915 in
      urban and 144 181 432 in rural areas). The percentage of morphologically verified
      cases and death certificate-only cases were 74.86% and 1.45%, respectively. The
      mortality to incidence ratio was 0.41. The estimates of new bladder cancer cases
      were 78 100 in China in 2014, with a crude incidence rate of 5.71/100 000. The
      age-standardized incidence rates by China standard population (ASR China) and
      world standard population (ASR world) of bladder cancer were 3.61/100 000 and
      3.56/100 000, respectively. Cumulative incidence rate of bladder cancer in China
      was 0.41%. The crude and ASR China incidence rates in urban areas were 6.88/100
      000 and 4.07/100 000, respectively, whereas those were 4.29/100, 000 and 2.96/100
      000 in rural areas. The estimates of bladder cancer deaths caused by bladder
      cancer were about 32 100 in China in 2014, with a crude mortality rate of
      2.35/100 000. The ASR China and ASR world mortality rates were both 1.30/100 000
      with a cumulative mortality rate (0-74 years old) of 0.12%. The crude and ASR
      China mortality rates were 2.79/100 000 and 1.41/100 000 in urban areas,
      respectively, whereas those were 1.81/100 000 and 1.14/100 000 in rural areas.
      Conclusions: The incidence and mortality pattern of bladder cancer were different
      in urban and rural areas. The incidence and mortality were higher in urban areas
      than that in rural areas, and higher for male than for female. We should focus on
      strengthening the prevention and control of bladder cancer in key population,
      especially men in urban areas.

PMID- 30293388
TI  - [Expression of granulocyte colony-stimulating factor receptor in colitis
      associated colonic carcinogenesis].
AB  - Objective: To investigate the expression of granulocyte-colony stimulating factor
      receptor (G-CSFR) in a mouse model of colitis-associated cancer (CAC), and the
      roles of G-CSFR positive immune cells in the development of CAC. Methods: The
      C57BL/6 mouse model of CAC was established by azoxymethane and dextran sulphate
      sodium. Three different stages in the development of CAC, including inflammation
      (AD1), mild dysplasia (AD2) and adenocarcinoma (AD3) were simulated. Colon tissue
      was digested into single cell suspension and the expressions of G-CSF and G-CSFR
      were analyzed by real-time PCR and fluorescence activated cell sorter (FACS). The
      expressions of G-CSFR on T cell, macrophage and neutrophil were analyzed by FACS.
      Results: The establishment of mouse model can effectively simulate the disease
      progression of CAC. The results of real-time PCR detection showed that the
      expression level of G-CSF mRNA in AD1, AD2 and AD3 groups were 1.2, 7.3 and 18.0
      fold changes of the control group, respectively. The differences between AD2, AD3
      and control groups were statistically significant (P<0.05). G-CSFR mRNA levels in
      AD1, AD2 and AD3 groups were 1.5, 2.2 and 4.5-fold changes of the control group,
      respectively. The difference between AD3 and control groups was statistically
      significant (P<0.05). FACS showed that the percentages of CD45(+) G-CSFR(+) cells
      in colorectal tissues of the control group, AD1, AD2 and AD3 groups were (21.84+/
      1.77)%, (41.48+/-4.15)%, (44.84+/-8.54)% and (57.76+/-1.95)%, respectively.The
      percentages of CD45(+) G-CSFR(+) cells in AD2 and AD3 groups were significantly
      higher than that of control group (P<0.05). The percentages of CD45(+) G-CSFR(+)
      macrophage in the colorectal tissues of the control group, AD1, AD2 and AD3
      groups were (21.54+/-5.88)%, (47.14+/-5.25)%, (42.49+/-7.80)% and (29.25+/
      8.24)%, respectively. The percentages of CD45(+) G-CSFR(+) T cells in these
      groups were (30.04+/-6.87)%, (29.65+/-8.08)%, (33.75+/-7.37)% and (33.32+/
      9.85)%, respectively. The percentages of CD45(+) G-CSFR(+) granulocyte were
      (2.39+/-2.10)%, (4.05+/-1.56)%, (3.62+/-2.67)% and (2.26+/-0.85)%, respectively
      (P<0.05). The percentages of G-CSFR(+) macrophage and G-CSFR(+) T cells were
      significantly higher than that of G-CSFR(+) granulocyte (P<0.05). The differences
      between AD1 and control group, AD2 and control group, AD1 and AD2 group, AD2 and
      AD3 group were statistically significant (P<0.05). Conclusions: The expression of
      G-CSFR is significantly up-regulated in the development of CAC. The enrichment of
      G-CSFR(+) macrophages in the colon tissue suggests G-CSFR(+) macrophages
      participate in the development of CAC.

PMID- 30293389
TI  - [Effects of FPR2 gene silencing on the proliferation, migration and invasion of
      human glioma U87 cells].
AB  - Objective: To investigate the effects of formyl peptide receptor 2 (FPR2)
      silencing on the proliferation, migration and invasion of human glioma U87 cells
      and its possible mechanisms. Methods: The expression of FPR2 was detected in
      normal glial cells, glioma cells, normal brain tissues and glioma tissues using
      Western blot and immunohistochemistry staining. A synthesized siRNA duplex was
      employed to inhibit FPR2 in human glioma cells (U87). The knockdown efficiency
      was evaluated by real-time reverse transcription-polymerase chain reaction (RT
      qPCR) and Western blot. MTT, transwell assays and flow cytometry analyses were
      used to determine the cell proliferation, migration, invasion and apoptotic rates
      of U87 cells, respectively. Mice xenograft experiments were used to observe the
      effect of FPR2 silencing on the tumorigenesis of U87 cells in vito. Western blot
      and enzyme-linked immunosorbent assays were performed to detect the expression
      and release of cell cycle and migration-related proteins. Results: The expression
      of FPR2 was significantly higher in glioma cell lines and glioma tissues than
      that in normal glial cells and brain tissues. Compared with blank control and
      negative control, FPR2 mRNA and protein levels in siRNA group were significantly
      downregulated. The cell proliferation inhibitory rates in FPR2 siRNA group were
      (23.1+/-5.1)%, (39.6+/-5.6)% and (44.4+/-6.7)% at 24 h, 48 h and 72 h,
      respectively, which were significantly increased than those in negative control
      group [(3.2+/-0.6)%, (5.7+/-0.8)% and (7.9+/-0.9)%, respectively; P<0.05]. The
      apoptosis rate in FPR2 siRNA group was (17.4+/-2.1)%, which was significantly
      elevated than that in the negative control group with (5.4+/-0.5)% and blank
      control group with (3.8+/-0.3)% (all P<0.05). In addition, the numbers of
      migrated cells were 108.7+/-9.5 in FPR2 siRNA group, which was significantly
      lower than that in blank control group 312.9+/-17.5 and negative control group
      (304.4+/-15.7, all P<0.05). Likewise, the numbers of invaded cells were 19.3+/
      3.2 in FPR2 siRNA group, which was significantly lower than that in blank control
      group 106.9+/-8.5 and negative control group (102.4+/-7.4, all P<0.05). Moreover,
      the growth of FPR2 siRNA transfected U87 cells in vivo was remarkably decreased
      comparing with the negative group (P<0.05). Furthermore, the expression of cyclin
      D1 and VEGF in FPR2 silencing U87 cells was suppressed mainly through beta
      catenin signaling pathway. Conclusions: FPR2 silencing by siRNA can inhibit the
      growth, migration and invasion ability, but promote the apoptosis of U87 cells.
      The possible mechanisms might be associated with the inhibitory expression of
      cyclin D1 and VEGF.

PMID- 30293390
TI  - [Relationship between c-kit mRNA expression and prognosis in patients with rectal
      carcinoma].
AB  - Objective: To investigate the correlation between c-kit mRNA expression and
      prognosis in patients with rectal carcinoma. Methods: The expression of c-kit
      mRNA in rectal carcinoma tissues(n=66) was detected by multiplex branched-DNA
      liquid chip method. According to the expression level, the patients were
      classified into the c-kit mRNA high expression group and the low group. We
      analyzed the relationship between the c-kit mRNA expression and the
      clinicopathological characteristics of patients, as well as the factors affecting
      patients'prognosis. Results: Of the 66 rectal carcinoma patients, 18(27.3%)cases
      were c-kit mRNA high expression. No significant correlation was found between the
      c-kit mRNA expression and gender, age, preoperative carcinoembryonic antigen,
      preoperative hemoglobin, distance to verge, lymph node metastasis, tumor
      thrombus, T stage, TNM stage and tumor differentiation (P>0.05). In follow-up, 34
      patients died, 32 patients and 36 patients were recurrence or metastasis. The 1-,
      3-, 5-year overall survival(OS) of c-kit mRNA high expression group were 100.0%,
      77.8%, 77.8%, respectively, while those of the low one were 93.8%, 56.3%, 45.8%,
      respectively. The difference was statistically significant(P=0.025). Lymph node
      metastasis, T stage and TNM stage were also significant associated with
      OS(P<0.05). The 1-, 3-, 5-year disease free rate (DFS)of the c-kit mRNA high
      expression group were 100.0%, 77.8% and 77.8%, respectively, while those of the
      low one were 77.1%,43.8% and 41.7%, respectively, and the difference between the
      two groups was significant (P=0.044). As a reslut, c-kit mRNA expression
      (P=0.038) and TNM stage (P=0.039) were the independent prognostic factors
      affecting the OS in rectal cancer patients. Conclusions: Low expression of c-kit
      was associated with poor prognosis of rectal carcinoma. And the mechanism
      underlying this phenomenon deserves further exploration.

PMID- 30293391
TI  - [The value of ultrasound classification in BI-RADS category 4 of breast complex
      cystic masses].
AB  - Objective: To analyze the feature of breast complex cystic masses and to classify
      it at ultrasonography (US), which applied to the Breast Imaging Reporting and
      Data System (BI-RADS) categories 4a to 4c with pathological results as the golden
      standards. Methods: The ultrasonographic data and clinical features of 78
      patients with complex cystic masses confirmed by pathology in Cancer Hospital
      from July 2014 to June 2017 were retrospectively reviewed. The complex cystic
      breast masses were divided into four classes on the basis of their US features:
      type 1 [thick wall and (or) thick septa (> 0.5 mm)], type 2 (one or more intra
      cystic masses), type 3 (mixed cystic and solid components with cystic components
      more than 50%) and type 4 (mixed cystic and solid components with solid
      components more than 50%). Positive values (PPVs) were calculated for each type.
      Multiple linear regression analysis was used to analyze the ultrasonographic
      features of the masses (lesion size, margins, blood flow resistance index,
      calcification, and axillary lymph nodes, etc.) with malignant correlation.
      Results: There were 81 lesions in 78 patients. Among the 81 masses based on US
      appearance, 14 (17.3%) were classified as type I, 18 (22.2%) as type II, 18
      (22.2%) as type III, and 31 (38.3%) as type IV. The positive predictive values of
      the malignant lesions of type I, type II, III and IV were 7.1%, 16.7%, 61.1% and
      48.3%, respectively (P=0.040). In all the 81 masses, 14 were BI-RADS categories
      4a, 18 were BI-RADS categories 4b and 49 were BI-RADS categories 4c. Masses with
      maximum diameter equal to or larger than 2.0 cm, unclear margins, RI>=0.7 and
      presence of abnormal axillary nodes assessment had a high probability of
      malignancy (P=0.030, 0.038, <0.001 and 0.025, respectively). Conclusion:
      Ultrasound typing is helpful for differentiating benign and malignant breast
      complex cysts and classifying BI-AIDS 4a to 4c, thus providing clearer treatment
      for clinical practice.

PMID- 30293392
TI  - [Relationship of CXCL14 level and the prognosis of patients with stage I-IIIA non
      small cell lung cancer after radical resection].

PMID- 30293393
TI  - [The association of metastasis-related indexes of lymph nodes and the prognosis
      of stage N2b colorectal cancer patients].
AB  - Objective: To evaluate the prognostic value of lymph node metastasis-related
      indexes in patients with stage N2b colorectal cancer. Methods: Clinicopathologic
      data of 245 patients with stage N2b colorectal cancer who initially underwent
      radical operation in Cancer Hospital, Chinese Academy of Medical Sciences between
      January 2007 and December 2012 were retrospectively analyzed. The prognostic
      values of several indexes, including number of positive lymph nodes, number of
      negative lymph nodes, lymph node ratio (LNR) and log odds of positive lymph nodes
      (LODDS) were analyzed. Results: The 5-year overall survival rate of 245 patients
      with colorectal cancer was 54.0%, and the 5-year recurrence-free survival rate
      was 48.5%.Univariate analysis showed that perineural or blood vessel invasion, T
      stage, postoperative adjuvant therapy, number of positive lymph nodes, number of
      negative lymph nodes, LNR, and LODDS were significantly associated with the 5
      year overall survival of colorectal cancer patients (P<0.05). Multivariate cox
      regression analysis showed that, number of positive lymph nodes, number of
      negative lymph nodes, LNR, LODDS were all independent prognostic factors for
      stage N2b colorectal cancer patients (P<0.05). The areas under the receiver
      operating characteristic curve (ROC) curves of number of positive lymph node,
      number of negative lymph nodes, LNR and LODDS were 0.649, 0.667, 0.690 and 0.683,
      respectively, however, no statistical significance was observed between the
      number of negative lymph nodes (P=0.622), LNR (P=0.178) or LODDS (P=0.272) and
      the number of positive lymph nodes. Conclusion: The number of positive lymph
      nodes, number of negative lymph nodes, LNR and LODDS were all independent
      prognostic factors for patients with stage N2b colorectal cancer.

PMID- 30293394
TI  - [Primary clear cell sarcoma of calcaneus: a rare case report].

PMID- 30293395
TI  - [Analysis of clinicopathological characteristics and prognostic factors of foot
      and ankle soft tissue and bone tumors].
AB  - Objective: To evaluate the clinicopathological characteristics of foot and ankle
      soft tissue and bone tumor, and to analyze the prognosis and the related factors
      of malignant tumors in this site. Methods: 74 patients with soft tissue and bone
      tumors of foot and ankle from January 2006 to February 2017 were retrospectively
      analyzed. The clinicopathological characteristics, the treatment and survival
      status of malignant tumors were followed up, and the clinical and therapeutic
      factors related to prognosis were analyzed. Results: Of the 74 patients, 34 were
      males and 40 were females. The male to female ratio was 1?1.18; the age ranged
      from 12 to 64 years and the median age was 42 years. Tumors located in forefoot
      of 22 cases, 22 in midfoot, 10 in hind foot, 14 in ankle joint and 6 in multiple
      sites. 14 cases were bone tumors, including 7 benign and 7 malignant, and 60
      cases were soft tissue tumors, including 14 benign and 46 malignant. The most
      common malignant soft tissue tumors were synovial sarcomas (13 cases), and the
      most common benign soft tissue tumors were hemangiomas (4 cases). 44 cases of
      malignant tumors underwent surgery were followed up, of which were 7 bone and 37
      soft tissue malignant tumors. Limb salvage surgeries were performed in 33 cases
      and amputation in 11 cases. The median follow-up time was 69.8 months, and the
      median survival time was 40.7 months. The 1-year, 3-year and 5-year survival rate
      of soft tissue malignant tumors was 88.0%, 73.0%, and 63.0%, respectively. The 1
      year, 3-year and 5-year survival rate of bone malignant tumors was 86.0%, 57.0%
      and 57.0%, respectively. Univariate analysis showed that the prognostic factors
      affecting 5-year survival rate were tumor size and adjuvant therapy (P<0.05).
      Patient's gender, age, tumor location, histological type and surgical procedure
      had no effect on overall survival(P>0.05). Multivariate analysis showed that
      tumor size was an independent prognostic factor (RR=7.262, P=0.005). Conclusions:
      Forefoot and midfoot are more common in foot and ankle soft tissue and bone
      tumors. Synovial sarcoma is the most common diagnosis in malignant soft tissue
      tumors, and hemangioma is the most common diagnosis in benign soft tissue tumors.
      The prognostic factor of malignant soft tissue and bone tumors in foot and ankle
      is tumor size. Patients with the tumor size of 5 cm or more have a worse
      prognosis.

PMID- 30293396
TI  - [Oncological safety and prognosis factors analysis of immediate breast
      reconstruction after nipple-areola-complex sparing mastectomy].
AB  - Objective: To explore the oncological safety of immediate breast reconstruction
      after nipple-areola complex(NAC) sparing mastectomy(NSM+ IBR) in patients with
      early stage breast cancer, and to analyze the prognostic factors of NSM+ IBR.
      Methods: From January 2004 to December 2015, the clinical data of 118 cases of
      stage I-IIA breast cancer who had undergone NSM+ IBR in Tianjin Tumor Hospital
      were collected, comparing with 75 cases of I-IIA breast cancer patients who had
      undergone immediate breast reconstruction after modified radical mastectomy (MRM+
      IBR) at the same period. In addition to the prognosis of these two groups, the
      prognostic factors were also retrospectively analyzed. Results: The median follow
      up were 53 months in the NSM+ IBR group and 51 months in the MRM+ IBR group,
      respectively. In the NSM+ IBR group, local recurrence, distant metastasis, death
      and NAC necrosis occurred in 4, 6, 9 and 4 cases during 3 years after operation,
      respectively. The local recurrence rate (LRR) was 3.4%, 3-year disease-free
      survival (DFS) rate was 91.5%, and the overall survival (OS) rate was 92.4%. In
      the MRM+ IBR group, local recurrence, distant metastasis, and death occurred in
      1, 4, and 3 cases during 3 years after operation, respectively. The LRR was 1.3%,
      3-year DFS was 93.3%, whereas the OS rate was 96.0%. No statistical difference
      was noted between the two groups (all P>0.05). That HER-2 positive and molecular
      type correlated with the 3-year DFS (P<0.05) independently and molecular type
      correlated with OS (P<0.05) independently in the NSM+ IBR group. Conclusions: NSM
      does not impair patients' prognosis and could ensure oncological safety of
      patients with early stage breast cancer. IBR could improve female patients'
      figure and ensure the quality of life. HER-2 status and molecular type are the
      independent prognostic factors of the 3-year DFS. Molecular type is the
      independent prognosis factor of OS.

PMID- 30293397
TI  - [Efficacy of lobaplatin plus S-1 and the predictive value of circulating tumor
      cell in patients with advanced gastric cancer].
AB  - Objective: To investigate the efficacy and safety of lobaplatin (LBP) plus S-1
      for advanced gastric cancer (AGC) and determine the potential role of circulating
      tumor cells (CTC) for predicting the therapeutic response and prognosis. Methods:
      From January 2014 to February 2015, 64 consecutive patients with AGC received
      lobaplatin plus S-1 chemotherapy in Liaocheng People's Hospital. The clinical
      features, clinical response, adverse effects, prognosis and CTC pre- and post
      treatment were retrospectively analyzed. The correlation between CTC and
      patients' disease control rate (DCR), objective response rate (ORR), progression
      free survival (PFS) as well as overall survival (OS) were investigated. Results:
      All 64 patients completed 2 cycles of chemotherapy.The number of patients who
      achieved complete regression, partial regression, stable and progression were 0,
      24 (37.5%), 18 (28.1%) and 22 (34.4%), respectively. ORR was 37.5% and DCR was
      65.6%. The median PFS was 10.8 months(95%CI 7.1-12.0) and the median OS was 16.1
      months(95%CI 12.4-18.8). The ORR and PFS were not significantly different between
      patients with baseline CTC>=2 and CTC<2 (25.0% vs 53.6%, P=0.150; 6.2 months vs
      7.5 months, P=0.780), while the DCR and OS were significantly different (45.9% vs
      90.0%, P=0.008; 10.5 months vs 17.2 months, P<0.001). After 2 cycles of
      chemotherapy, the ORR and DCR in patients with CTC>=2 were 16.7% and 45.9%,
      respectively, which were significantly lower than those observed in patients with
      CTC<2 (50.0% and 90.0%, respectively). The former also had shorter median PFS and
      OS (6.6 months vs 8.9 months, 8.4 months vs 15.0 months, respectively). Patients
      with persistently CTC<2 or those exhibiting an conversion to CTC<2 following
      chemotherapy had an improved PFS and OS, while patients with persistently CTC>=2
      or those exhibiting an conversion to CTC>=2 following therapy had shorter PFS and
      OS.The most frequent adverse effects were grade 1 or 2 gastrointestinal
      discomfort and myelosuppression. No patients discontinued chemotherapy because of
      adverse events. Conclusions: Lobaplatin plus S-1 had manageable safety profile
      and promising antitumor activity in patients with AGC. CTC could be used as a
      biomarker in evaluating therapeutic response and predicting their prognosis.

PMID- 30293398
TI  - [Chinese expert consensus on the clinical diagnosis and treatment of advanced
      breast carcinoma(2018)].
AB  - Breast cancer is the most common malignant tumor among women in the world. In
      2015, there were about 272 000 new diagnosed cases and over 70 000 deaths of
      breast cancer in China. In new cases of breast cancer each year, about 3 to 10
      percent have distant metastases at the time of diagnosis. Among the early-stage
      patients, 30%-40% will develop into advanced breast cancer. The 5-year survival
      rate of patients with the advanced breast cancer is only 20%, and the overall
      median survival is 2-3 years. Although advanced breast cancer is still difficult
      to cure at present, we can relieve the clinical symptoms, improve the quality of
      life and further prolong the survival time through development of new drugs and
      the optimization model of treatment. Patients with advanced breast cancer have
      their own particularity in the choice of treatment options. Moreover, there is no
      standard recommendation for the treatment of refractory breast cancer after
      multiline therapy. In order to offer reference for clinicians, the Chinese expert
      group has analyzed, summarized and discussed the related research data of
      diagnosis, treatment and prognosis of inoperable locally advanced breast cancer
      and recurrent or metastatic breast cancer, and developed the Chinese expert
      consensus on the clinical diagnosis and treatment of advanced breast carcinoma
      (2018).

PMID- 30293399
TI  - [Consensus on clinical diagnosis, treatment and prevention management of
      chemotherapy induced thrombocytopenia in China(2018)].
AB  - Chemotherapy induced thrombocytopenia (CIT) is a common side-effect of
      chemotherapy in cancer patients, which lead to dose and cycle reduction or
      chemotherapy delay, or even the need of platelet transfusion. Therefore, CIT
      significantly increases the cost of treatment, reduces the efficacy of
      chemotherapy and the quality of life, and shortens the survival time of patients.
      The main treatments of CIT include transfusion of platelets, recombinant human
      thrombopoietin (rhTPO), and recombinant human interleukin-11 (rhIL-11). RhIL-11
      is the first approved thrombocytopoietic cytokine. Interleukin-11 has been shown
      to be effective in the treatment of thrombocytopenia. RhTPO is a recombinant full
      length glycosylated thrombopoietin, which is a ligand for c-Mpl protein. Several
      observations indicated that administration of rhTPO before and after chemotherapy
      might be beneficial to patients, which enhances platelet recovery and reduces
      thrombocytopenia after moderately myelosuppressive regimens. In recent years, the
      application of rhTPO in CIT treatment has dramatically changed the management and
      treatment plan of CIT. The China Society of Clinical Oncology (CSCO) published a
      consensus on CIT in 2014. Based on this, the expert committee updated "Consensus
      on clinical diagnosis, treatment and prevention management of chemotherapy
      induced thrombocytopenia in China (2018)" according to the recent literature and
      clinical research. The new evidence-based practice consensus for CIT aims to
      provide more reasonable diagnosis, treatment of prevention regimens for CIT
      patients to maintain the normal platelet counts.

PMID- 30293400
TI  - Postpartum stretchmarks: repairing activity of an oral Centella asiatica
      supplementation (Centellicum(r)).
AB  - BACKGROUND: This registry study evaluates the effects of oral Centellicum(r), a
      new preparation of Centella asiatica (CA) on cutaneous stretchmarks (SMs) on the
      lower abdominal wall in comparison with the topical treatment with a specific
      antistretch cream. This cream is used for pregnancy SMs. The aim of the
      management was to give back to the structurally damaged skin areas (apparent as
      SMs) a normal elasticity and resistance and improving the local microcirculation.
      METHODS: We selected 78 healthy women with SMs at least 6 months postpartum
      available to follow the registry plan. The subjects were evaluated in three
      treatment groups: Clarins, stretch mark minimizer, the hydrating control cream
      and Centellicum(r) 3X225 mg/day for 6 weeks. RESULTS: The three registry groups
      of otherwise healthy subjects were comparable at inclusion and 6 weeks: 25 women
      used the SMs cream 1 (mean age 34.4;3.2); 28 control women (age 35.2;2) used the
      hydrating control cream. The third group (25 women; mean age 35.3;1.5) used the
      hydrating control cream and oral Centellicum(r) as a supplementary management.
      Standard management was used in all groups. As for the safety issue, no allergy,
      no side effects and no tolerability problems were observed. The compliance was
      very good and there were no drop outs. No other drug or treatment was used during
      the registry period. Skin thickness (ultrasound, measuring at the edge of at the
      largest visible stretchmark) increased significantly more at 6 weeks with
      Centellicum(r) in comparison with both controls (P<0.05). Skin thickness at the
      center of the SM (skin was less dense at this level) was also increased more with
      the supplement in comparison with the other managements (P<0.05). The grey scale
      median improved more (increased) with Centellicum at 6 weeks (P<0.05). The skin
      included more collagen components and become whiter or denser at ultrasound. Skin
      perfusion measured by laser Doppler showed a higher improvement with
      Centellicum(r) (P<0.05). Skin temperature, considered a function of nutritional
      and thermoregulatory dermal perfusion, improved more with the supplement
      (P<0.05). Elasticity (measured by elastosonography) was improved more with the
      supplement (P<0.05). The subjective evaluation with an analogue score resulted
      better (the SMs were less visible and the score decreased) with Centellicum(r)
      (P<0.05). The number of visible SMs was decreased more with Centellicum(r)
      (P<0.05). CONCLUSIONS: Oral supplementation with Centellicum(r) appears to
      improve SMs in a relatively short period of time. Larger studies are needed to
      evaluate the protective and repairing potentials of CA.

PMID- 30293401
TI  - An innovative approach to evaluate preeclampsia risk in the first trimester of
      pregnancy.

PMID- 30293402
TI  - Novel sonographic method for the evaluation of the defects in the pubocervical
      fascia in patients with genital prolapse.

PMID- 30293403
TI  - Changes in rectus femoris architecture induced by the reverse nordic hamstring
      exercises.
AB  - BACKGROUND: Injuries and mechanical stimuli alter the muscle architecture and,
      therefore, its function. The changes in the architecture of the Rectus Femoris
      (RF) induced by an eccentric training protocol with Reverse Nordic Hamstring
      exercises (RNHE) have never been studied. Therefore, the aim of the present study
      was to determine the architectural adaptations of the Rectus Femoris (RF) after
      an eccentric training with Reverse Nordic Hamstring exercises (RNHE), followed by
      a subsequent detraining period. METHODS: The 26 subjects performed a first week
      of control, 8 weeks of eccentric training, concluding with a 4-week period of
      detraining. The architectural characteristics of the RF were evaluated using 2D
      ultrasound at rest (pretest - week 1), after the training (posttest - week 9),
      and at the end of the detraining period (retest - week 13). RESULTS: At the end
      of the training period, a significant increase in the muscle fascicle length (FL)
      (t=-8.96, d=2.22, P< 0.001), muscle thickness (MT) (t=-8.76, d=2.219, P< 0.001),
      pennation angle (PA) (t=-9.83, d=2.49, P< 0.05) and cross-sectional area (CSA)
      (t=- 13.06, d=3.06, P< 0.001) was observed. After the detraining period FL, MT,
      PA and CSA showed a significant decrease. CONCLUSIONS: The eccentric training
      with RNHE may cause changes in the architectural conditions of RF, which, in
      addition, are also reversible after a 4-week detraining period. The adaptations
      produced by RNHE may have practical implications for injury prevention and
      rehabilitation programs, which include the changes in muscle architecture
      variables.

PMID- 30293404
TI  - Changes in diet, and the relationship between diet and physical activity, within
      and across the lifetime of current ultra-endurance exercisers.
AB  - BACKGROUND: There is currently no information on the lifetime diet of ultra
      endurance exercisers. This study describes changes in diet across the lifetime of
      current ultra-endurance exercisers and the relationship between diet and physical
      activity (specifically ultra-endurance exercise [UEE]). METHODS: Lifetime
      physical activity and diet were assessed in current ultra-endurance exercisers
      (n=120; ages 21-74 years) over six life periods (5-12, 13-18, 19-30, 31-45, 46
      60, 61-75 years). Using the life period having the largest absolute increase in
      UEE (IUEE), diet was assessed according to food category scores and dietary
      patterns. Changes in lifetime diet were described by comparing food category
      scores between adjacent life periods. Differences in food category scores were
      investigated between the life period for each IUEE group and the preceding life
      period and associations between dietary patterns and UEE were investigated within
      each IUEE group. Relationships between lifetime diet and UEE were investigated by
      examining associations between lifetime food category scores and lifetime UEE.
      RESULTS: The participant group had significant increases in all food category
      scores from 13-18 to 19-30 years and significant decreases in all food category
      scores from 19-30 to 31-45 years. UEE correlated negatively with the Western
      style dietary pattern in the IUEE19- 30 group and positively with the fruit and
      vegetable dietary pattern in the IUEE31-45 group. There was a positive
      correlation between lifetime UEE and lifetime vegetables and fruit category
      scores. CONCLUSIONS: The ultra-endurance exercisers in this study exhibited
      changes in diet similar to general populations, which appear to reflect typical
      nutritional requirements across the lifespan.

PMID- 30293405
TI  - Therapeutic validity of exercise interventions in the management of fibromyalgia.
AB  - BACKGROUND: This study aimed (1) to evaluate the therapeutic validity of exercise
      interventions included in a previous umbrella systematic review of high-quality
      randomized controlled trials (RCTs) in the management of fibromyalgia; and (2) to
      explore whether exercise interventions with high therapeutic validity and that
      meet the 2013 American College of Sports Medicine (ACSM) guidelines are
      positively associated with greater pain relief. METHODS: Therapeutic validity was
      evaluated based on the CONsensus on Therapeutic Exercise and Training (CONTENT)
      scale, in high methodological quality RCTs found in the nine systematic reviews
      of a previous umbrella review on exercise interventions in the management of
      fibromyalgia. Additionally, the compliance of the 2013 ACSM exercise
      recommendations for fibromyalgia was analyzed. The effect size for pain relief
      after the exercise programs was also considered. RESULTS: The CONTENT mean total
      score was 4.42 out of 9, demonstrating generally low therapeutic validity of the
      28 included RCTs. There was poor concordance between therapeutic validity and
      pain relief (Kappa values ranging between -0.6 to 0.57). Kappa statistic results
      showed poor concordance (k=0.01) between statistically significant (p<0.05) pain
      relief values and achievement of 2013 ACSM exercise recommendations. CONCLUSIONS:
      The therapeutic validity of exercise intervention programs in fibromyalgia is
      low. This is mainly due to incomplete descriptions of exercise interventions and
      adherence. Poor concordance is found between high therapeutic validity and
      accomplishment of the ACSM exercise recommendations with pain relief. Improved
      standardized reporting is recommended to identify optimal exercise prescription
      for fibromyalgia.

PMID- 30293406
TI  - Effects of a home based exercise rehabilitation program for cancer survivors.
AB  - BACKGROUND: Aerobic and resistance exercises have been promoted recently to
      improve quality of life in cancer patients. Most cancer survivorship
      rehabilitation programs consists of supervised exercise programs; however, less
      data is available on the effects of unsupervised or home-based exercise
      interventions. The study aimed to compare the physical and physiologic changes in
      a group of cancer survivors (CS) and a control group of non-cancer, health
      controls (HC) who participated in individualized home-based aerobic and
      resistance exercises for 12 months. METHODS: Thirty-three surviving cancer
      survivors (CS) aged 55.6+/-3 y were enrolled for 1 year of unsupervised exercise
      prescription programs. Anthropometric parameters hydration status, fitness, and
      echocardiographic examination were measured every six month and compared to10 HC
      (aged 52.6 +/- 7.7 y) individuals prior to starting the program (t0) and at 6
      (t6) and 12 (t12) months. RESULTS: Among the CS subjects a significant reductions
      in waist circumference t0: 97.5 +/-15.2; t6: 86.6 +/-13.5; t12: 85.8 +/- 13.9,
      p<0.05; body cell mass% t0: 50.9+/-4.7; t6: 52.3+/-4.4; t12: 53.7+/-3.7; p<0.05
      and extracellular mass %, t0: 49.1+/-4.7 t6; 47.6+/-4.4, t12: 46.2+/-3.7, p <
      0.05, were observed as well significant improvements in lower body muscle
      strength (chair test t0:13.3+/-4.1, t6: 14.2+/-3.5, t12: 15.1+/-3.2; p<0.05).
      Changes in functionality and heart function were similar between CS and HC's.
      CONCLUSIONS: Individually prescribed home-based exercise programs were cost
      effective, safe and resulted in modest improvements in body composition,
      strength, and total body water distribution with little to no adverse effect on
      cardiac function.

PMID- 30293407
TI  - Nutrition, hydration and ergogenic aids strategies in ultraendurance mountain
      events.
AB  - BACKGROUND: The purpose of the present research was to analyze nutrition,
      hydration and ergogenic aids strategies in ultraendurance mountain events.
      METHODS: A total of 386 ultra endurance mountain races finishers were analyzed.
      They were divided into three groups according to their race distance: G1:
      distance less than 45 km (n: 250); G2 distances between 45 and 90 km (n: 71); G3
      distances longer than 90 km (n: 65). The ergogenic, nutritional and hydration
      strategies were quantified after each race by a questionnaire. RESULTS: We found
      a higher ingestion of (0.56 +/- 0.95), caffeine (G3 M+/-SD; 203.8+/-211.5 mg),
      water (G3 M+/-SD; 7.1+/-3.7 l) and Portion of Sandwich (nutrition 5.3+/-7.4)
      NSAID in longer distance probes. Higher performance runners in low and medium
      distances consumed a significantly (p>0.05) lower quantity of gels (higher 0.76+/
      0.98 vs lower 1.38+/-1.38), and muesli bar (higher 1.09+/-1.13 vs lower 2.04+/
      1.94), and in long distances. Higher performance consumed more water (M+/-SD;
      higher 8.23+/-3.92 vs lower 6.12+/-3.28) than lower performance ones. They also
      could maintain a higher rated of perceived exertion than lower performance (G3
      M+/-SD; higher 16.7+/-2.28 vs lower 18.2+/-1.71). CONCLUSIONS: Higher distance
      presented higher nutritional, caffeine and NSAIDs ingestion than lower distances,
      also, higher performance athletes of higher distance presenter higher water and
      nutritional ingestion than lower performance ones. In Lower distance probes,
      higher performance athletes presented lower hydration and nutritional ingestion
      than lower performance athletes.

PMID- 30293408
TI  - Bench press performance during an intermittent hypoxic resistance training to
      muscle failure.
AB  - BACKGROUND: Resistance training performed under hypoxia conditions has been shown
      to cause major metabolic and hormonal responses. However, the influence of
      hypoxia on an acute session has been barely studied. The aim of this study was to
      evaluate the acute effects of an intermittent hypoxic resistance training (IHRT)
      to muscle failure on bench press performance. METHODS: A randomized crossover
      design was performed, and 25 untrained men performed a resistance training under
      two different conditions: normoxia (FIO2=21%) and high-level hypoxia (FIO2=13%).
      Resistance training consisted of 3 sets of 75% 1RM to muscle failure, with a 2
      minute rest between sets. Physical performance were assessed by quantifying total
      repetitions, concentric velocity and power variable during all sets. Arterial
      oxygen saturation, heart rate, rating of perceived exertion (RPE), capillary
      blood lactate and muscle soreness were also assessed after training. RESULTS:
      Physical performance during bench press did not differ under hypoxic conditions
      (p>0.05). However, there were significant increases (p<0.05) of RPE (from 7.5 +/-
      0.8 to 7.9 +/- 0.8) and blood lactate concentrations (from 5.5 +/- 1.2 to 6.2 +/-
      1.5 mmol/L) in the hypoxia group. CONCLUSIONS: These findings suggest that
      hypoxic resistance exercise does not affect exercise performance during bench
      press exercise. However, influence to perceived exercise intensity and blood
      lactate concentrations, suggesting that hypoxic resistance training may add
      substantially to the training dose experienced.

PMID- 30293409
TI  - Pre-cancer diagnosis cardiorespiratory fitness, physical activity and cancer
      mortality in men.
AB  - BACKGROUND: The preventive role of pre-cancer diagnosis cardiorespiratory fitness
      (CRF) and physical activity (PA) in cancer mortality is poorly characterized.
      AIM: To assess the association between CRF, PA at pre-cancer-diagnosis and cancer
      mortality in men who diagnosed with cancer later in life. METHODS: A total of 699
      men (63+/-10 years) who were diagnosed with cancer during 7.5+/-4.9 years from a
      baseline treadmill exercise test and reported PA were analyzed. Multivariate Cox
      models for CRF and univariate model for PA were conducted. Population
      Attributable Risks (PARs%) and Exposure Impact Number (EIN) of low CRF (<5 METs)
      and inactivity were determined. RESULTS: During 6.5+/-5.2 years from cancer
      diagnosis, 56% died from cancer. CRF was inversely, graded and independently
      associated with cancer death. A 1-MET increase and categories of moderate and
      high CRF were associated with 7%, 28% and 51% reductions in risk of cancer death,
      respectively. Active compared to inactive individuals had a 23% reduced risk of
      cancer mortality [HR=0.77, 95% CI (0.63-0.94), p=0.01]. PARs% of low CRF and
      inactivity were 4.8% and 9.4%, respectively, while the respective EIN were 3 and
      9. CONCLUSIONS: Higher CRF and being active at pre-cancer-diagnosis were
      associated with lower cancer mortality and longer survival time in men who
      developed cancer later in life. Screening and intervening for low CRF and
      inactivity as risk factors during middle-age and maintaining at least moderate
      CRF and activity levels may be effective strategies for prevention of cancer
      mortality.

PMID- 30293410
TI  - The provision of simple written material does not significantly improve physical
      activity rates in a population with musculoskeletal problems, a double-blinded
      randomised controlled trial.
AB  - BACKGROUND: Physical activity has been shown to have significant health benefits
      to individuals, being effective in the treatment and prevention of multiple
      different conditions. However, despite these benefits, rates of physical activity
      remain low in the western world and less than 40% of people in the UK meet
      physical activity recommendations. Musculoskeletal pain can be a barrier to
      activity, and patients with pain can stop all activity out of fear of harm. This
      project seeks to see if simple written advice can influence activity rates and
      behaviours. METHODS: A double-blinded randomised controlled trial was conducted
      to assess any impact of simple written material on physical activity rates in
      patients attending a single UK National Health Service (NHS) Sports Medicine
      Department. 546 consecutive patients with a range of musculoskeletal problems
      were randomised to either an "intervention group" (n=235) or "control group"
      (n=311). Patients in the intervention group received simple written material
      encouraging of the benefits of physical activity for general aspects of health,
      including practical steps to increase regular activity in daily life such as
      commuting, and work. RESULTS: No significant difference in activity rates were
      seen between the members of the two groups in any of the outcome measures used.
      These measures included the short-form/7-day recall version of the International
      Physical Activity Questionnaire (IPAQ), the General Practitioner Physical
      Activity Questionnaire (GPPAQ), and the "Vital Signs" questions. There were no
      differences seen in transport choices. Overall physical activity levels were low
      among both groups, with only one-third reaching national targets of 150minutes of
      moderate-level physical activity per week, and one in five patients undertaking
      no regular physical activity. CONCLUSIONS: The provision of simple written
      material does not significantly improve physical activity rates in patients
      referred to this NHS Sports Medicine Clinic in the UK. Consideration must be
      given to more tailored and individualised approached to physical activity
      promotion.

PMID- 30293411
TI  - Extracorporeal shock wave therapy for isokinetic muscle strength around the knee
      joint in athletes with patellar tendinopathy.
AB  - BACKGROUND: The aim of this study was to explore the efficacy of 16 weeks of
      extracorporeal shockwave therapy in athletes with patellar tendinopathy. METHODS:
      Athletes with patellar tendinopathy were matched for age, height and body weight
      and assigned to the experimental group (n=26) or control group (n=25). Subjects
      in the experimental group received 16 rounds (once per week) of extracorporeal
      shockwave therapy (2,000 single shocks; strength, 1.5 to 3.0 bar; shock
      frequency, 9 to 12 Hz). Subjects in the control group received physical
      treatments, such as acupuncture, ultrasonic wave, and microwave therapy. RESULTS:
      After 16 weeks, VAS score in the experimental group was reduced by 69.4% (P<0.01)
      compared with that at 0 weeks. Knee joint 60 degrees /s and 240 degrees /s peak
      torques were increased by 17.2% (P<0.01) and 7.2% (P<0.05), respectively, and
      extensor endurance by 17.4% (P<0.05). VAS score in the control group was reduced
      by 16.9% (P<0.01) at 16 weeks compared with 0 weeks, and the knee joint 60
      degrees /s peak torque was increased by 8.2% (P<0.05). For between-groups
      comparisons, the VAS score in the experimental group was reduced by 62.7%
      (P<0.01); whereas knee joint 60 degrees /s and 240 degrees /s peak torques
      increased by 8.8% and 5.8%, respectively, and extensor endurance by 12.5%
      (P<0.05). There were no significant differences between male and female subjects
      (P>0.05). CONCLUSIONS: Extracorporeal shock wave therapy has a positive effect on
      patellar tendinopathy in athletes, with no gender differences in therapeutic
      effect. Extracorporeal shock wave therapy may be used to alleviate pain and
      improve knee joint extensor strength and endurance.

PMID- 30293412
TI  - Injury patterns in professional motorbike racing: a retrospective analysis of 728
      falls.
AB  - BACKGROUND: In professional motorbike racing falls with high velocities are
      common. Nonetheless, severe injuries or deaths are rare when compared to regular
      road traffic. METHOD: In this study, falls in all courses of the largest German
      race series IDM*Superbike between 2007 and 2013 were analyzed regarding injury
      patterns and hospital admissions. All races were accompanied by a medical team,
      including at least one physician who assessed every patient. RESULTS: 728 falls
      were included. A specific fall mechanism could be determined in 45.5% of the
      cases. 40.5% were admitted to a trauma center for further diagnostics. A
      definitive diagnosis was found in 45.4%. In most cases (29.9%) the injury pattern
      was a fracture of the extremities. In collisions a significantly higher odds
      ratio of 2.52 (p=0.0001) and in indeterminate falls a significantly lower odds
      ratio of 0.47 (p<0.0001) was observed. CONCLUSIONS: Fall patterns in professional
      motorbike racing do not significantly correlate with the severity of the injury.
      Thus, as in regular patient evaluation, each patient has to be examined
      thoroughly to avoid misinterpretation.

PMID- 30293413
TI  - Radiofrequency hemorrhoidectomy: less is less? Results of a comparative study.
AB  - BACKGROUND: Radiofrequency has been introduced as an instrument conceived to
      upgrade the conventional treatment of hemorrhoidectomy. To reduce the economic
      aspect, recently has been introduced a new radiofrequency device: VojantTM. Aim
      was to compare clinical outcomes of hemorrhoidectomy with LigaSureTM and
      VojantTM, performed with the Milligan- Morgan technique, in medium-term
      perspective. METHODS: Between January 2016 and December 2016, 50 consecutive
      patients with symptomatic grade III and IV were scheduled for surgical treatment.
      Patients were assigned randomly to undergo either VojantTM or LigaSureTM
      haemorrhoidectomy. All preoperative and postoperative data were collected.
      RESULTS: Patients in the LigaSureTM group experienced less pain than those
      treated by VojantTM, (p<0.05). In VojantTM group one patient developed immediate
      postoperative bleeding (within 48 h), the other one seven days after surgery.
      Complete wound healing and return to work activities was faster in LigasureTM
      group (p<0.05). One stenosis in LigasureTM group and two cases in VojantTM group
      were detected (p>0.05). CONCLUSIONS: Radiofrequency hemorrhoidectomy with
      VojantTM seems a valid alternative to Ligasure hemorrhoidectomy.

PMID- 30293414
TI  - Negative payoffs of upper gastrointestinal endoscopy in patients admitted under
      observation status.
AB  - BACKGROUND: More than 70 million americans (23% of the US population) have non
      cardiac chest pain at least once in their lifetime with gastroesophageal reflux
      disease (GERD) being the leading cause (37-66%). Current guidelines support the
      use of a proton pump inhibitor (PPI) prior to invasive or noninvasive testing as
      a diagnostic, therapeutic and cost effective method as a part of High Value Care
      recommendations. METHODS: We performed a chart review of 126 patients admitted to
      the hospital under observation status who underwent upper GI endoscopies in the
      hospital at 3 different urban community hospitals. This was compared with 260
      patients admitted who didn't have this procedure done. We calculated the
      healthcare burden including length of stay, reimbursement and complications from
      the procedures/extra stay in the hospital. RESULTS: The direct cost per case was
      almost two times in the group that underwent the procedure as compared to the
      group that did not. The mean LOS was higher in the group that underwent the
      endoscopies. There were no complications and there was no difference in
      mortality. CONCLUSIONS: Upper gastrointestinal endoscopy in patients with
      atypical chest pain of GI origin as an initial step is a significant healthcare
      burden and contradicts the currently recommended High Value Care recommendations.
      Our study delineates this large negative financial impact when performing upper
      endoscopies under observation status. Such patients should be started on an
      empirical trial of PPI, and endoscopy should be reserved for patients whose
      symptoms are unresponsive to PPIs or have alarm features.

PMID- 30293415
TI  - Symptoms and dietary practices of irritable bowel syndrome patients compared to
      controls: results of a United States National survey.
AB  - BACKGROUND: Little is known regarding the dietary behaviors and epidemiology of
      irritable bowel syndrome (IBS) patients in the United States (US). METHODS: This
      was an IRB-approved cross-sectional survey conducted via a secured online server
      (SurveyMonkey(r)). A representative sample of the US population were queried
      regarding demographics, gastrointestinal (GI) symptoms, treatments and dietary
      practices. Of 1,718 respondents, 161 reported IBS. These were compared to 1,116
      subjects reporting no GI diagnosis (controls). RESULTS: Overall, 9% reported a
      diagnosis of IBS. When compared to controls, IBS patients were more likely over
      45 years (p<0.001) and female (p<0.001). IBS patients more frequently noted
      abdominal pain, constipation, diarrhea, gas/bloating and GERD/heartburn (all
      p<0.001) than controls. Regarding therapeutic measures, IBS patients were more
      likely to cite food avoidance, over-the-counter remedies, probiotics,
      consultation with doctor/dietitian, and prescriptions (all p<0.001). However,
      they were less likely to believe their strategies were effective. While the
      majority of subjects believed food contributed to their symptoms, those with IBS
      listed more dietary triggers. IBS patients were more likely to follow a dietary
      'plan' with 21% citing lactose-free, 17% gluten-free and 9% low-FODMAP (all
      p<0.001). Nevertheless, 47% with IBS denied following any dietary plans. A
      minority, (24%), of IBS patients was aware of the low- FODMAP diet. CONCLUSIONS:
      In this US survey, IBS was reported by 9% of the population, most often females
      over 45 years. IBS patients were more likely to implement therapeutic strategies
      and cite food triggers, yet few were aware of the low-FODMAP diet. Outreach
      programs could improve awareness of this substantiated intervention.

PMID- 30293416
TI  - Diverticulosis today.
AB  - The incidence of diverticulosis and diverticular disease of the colon is
      increasing worldwide. Although the majority of patients remains asymptomatic long
      life, the prevalence of diverticular disease of the colon, including acute
      diverticulitis, is substantial and is becoming a significant burden on National
      Health Systems in terms of direct and indirect costs. Fiber, non-absorbable
      antibiotics and probiotics seem to be effective in treating symptomatic and
      uncomplicated patients, and 5-aminosalicylic acid might help prevent acute
      diverticulitis. Unfortunately, robust evidence on the effectiveness of a medical
      strategy to prevent acute diverticulitis recurrence is still lacking. Focus is
      now being drawn on identifying a new endoscopic classification of the disease to
      evaluate the correct therapeutic approach by testing various treatments.

PMID- 30293417
TI  - Prevalence of Helicobacter pylori infection among dyspeptic patients with and
      without type 2 diabetes mellitus in South-West and South-South regions of
      Nigeria.
AB  - BACKGROUND: This multicenter study was undertaken to determine the prevalence of
      Helicobacter pylori (H. pylori) infection among dyspeptic patients with and
      without type 2 diabetes mellitus (T2DM). METHODS: Patients with dyspepsia were
      recruited from tertiary teaching hospitals, three in the South-West and one in
      the South-South regions of Nigeria, between November 2016 and August 2017. The
      participants had breath samples analyzed for H. pylori by the Urea Breath Test
      (UBT) following manufacturer's instructions. Dyspeptic patients who were
      diagnosed previously with T2DM were recorded. Crosstab using chi-square and
      correlation analyses were used to test (hypothesis) variables. RESULTS: The
      entire cohort included 471 dyspeptics, 19 (4%) of whom had T2DM. H. pylori
      infection was reported in 232/471 (49.3%) dyspeptics and 13/19 T2DM patients,
      without significant difference between diabetics and nondiabetics. The majority
      (84.6%) of those positive for UBT and T2DM were in the age group 52-71 years,
      while none was in the age group 72-91 years. There was no statistical
      significance (p>0.05) between the age group, UBT and T2DM positive. CONCLUSIONS:
      Our study showed that, in Nigeria, there is no difference in prevalence of H.
      pylori in dyspeptic patients with and without T2DM.

PMID- 30293418
TI  - Single Molecule Profiling of Molecular Recognition at a Model Electrochemical
      Biosensor.
AB  - The spatial arrangement of target and probe molecules on the biosensor is a key
      aspect of the biointerface structure that ultimately determines the properties of
      interfacial molecular recognition and the performance of the biosensor. However,
      the spatial patterns of single molecules on practical biosensors have been
      unknown, making it difficult to rationally engineer biosensors. Here, we have
      used high-resolution atomic force microscopy to map closely spaced individual
      probes as well as discrete hybridization events on a functioning electrochemical
      DNA sensor surface. We also applied spatial statistical methods to characterize
      the spatial patterns at the single molecule level. We observed the emergence of
      heterogeneous spatiotemporal patterns of surface hybridization of hairpin probes.
      The clustering of target capture suggests that hybridization may be enhanced by
      proximity of probes and targets that are about 10 nm away. The unexpected
      enhancement was rationalized by the complex interplay between the nanoscale
      spatial organization of probe molecules, the conformational changes of the probe
      molecules, and target binding. Such molecular level knowledge may allow one to
      tailor the spatial patterns of the biosensor surfaces to improve the sensitivity
      and reproducibility.

PMID- 30293419
TI  - Sealable Spherical Mesoporous Silica Shell Nanoreactors as Fiducial Nanoscale
      Probes for X-rays.
AB  - Molecular reactions in aqueous solutions are often used as dosimetric probes. A
      major problem with this approach is that other species such as nanoparticles or
      radical scavenging chemicals can often interfere with these reactions. The
      results measured in the presence of nanomaterials and scavengers therefore cannot
      correctly indicate the true dose based on the calibrated results obtained in
      solutions free of the interfering species. Storing these molecular probes in
      nanoreactors can overcome this problem. Here we demonstrate for the first time
      that it is possible to place common probe molecules inside spherical mesoporous
      silica shells and seal the pores after impregnation for the purpose of using the
      so-formed nanoreactors as X-ray dose probes. The reactions are isolated from the
      external environment, while the sealed shells still allow X-rays to freely
      penetrate through the walls of the nanoreactors. These nanoreactor probes can
      therefore fiducially report the dose of X-rays, whether the nanoreactors are in
      solutions, in dry form, or in the presence of scavengers and catalysts in
      solution.

PMID- 30293420
TI  - From Acetoin to ( Z)-3-Hexen-1-ol: The Diversity of Volatile Organic Compounds
      that Induce Plant Responses.
AB  - Evidence that plants can respond to volatile organic compounds (VOCs) was first
      presented 35 years ago. Since then, over 40 VOCs have been found to induce plant
      responses. These include VOCs that are produced not only by plants but also by
      microbes and insects. Here, we summarize what is known about how these VOCs are
      produced and how plants detect and respond to them. In doing so, we highlight
      notable observations we believe are worth greater consideration. For example, the
      VOCs that induce plant responses appear to have little in common. They are
      derived from many different biosynthetic pathways and have few distinguishing
      chemical or structural features. Likewise, plants appear to use several
      mechanisms to detect VOCs rather than a single dedicated "olfactory" system.
      Considering these observations, we advocate for more discovery-oriented
      experiments and propose that future research take a fresh look at the ways plants
      detect and respond to VOCs.

PMID- 30293421
TI  - Only Para-Hydrogen Spectroscopy (OPSY) Revisited: In-Phase Spectra for Chemical
      Analysis and Imaging.
AB  - We revisited only para-hydrogen spectroscopy (OPSY) for the analysis of para
      hydrogen-enhanced NMR spectra at high magnetic fields. We found that the sign of
      the gradients and interpulse delays are pivotal for the performance of the
      sequence: the variant of double-quantum filter OPSY, where the second time
      interval is twice as long as the first one (OPSYd-12) converts the antiphase
      spectrum to in-phase and efficiently suppresses the background signal in a single
      scan better than the other variants. OPSYd-12 strongly facilitates the analysis
      of para-hydrogen-derived NMR spectra in homogeneous and inhomogeneous magnetic
      fields. Furthermore, the net magnetization produced is essential for subsequent
      applications such as imaging, e.g., in a reaction chamber or in vivo.

PMID- 30293422
TI  - Comprehensive Molecular Characterization of Atmospheric Brown Carbon by High
      Resolution Mass Spectrometry with Electrospray and Atmospheric Pressure
      Photoionization.
AB  - Light-absorbing components of atmospheric organic aerosols, which are
      collectively termed "brown carbon" (BrC), are ubiquitous in the atmosphere. They
      affect absorption of solar radiation by aerosols in the atmosphere and human
      health as some of them have been identified as potential toxins. Understanding
      the sources, formation, atmospheric evolution, and environmental effects of BrC
      requires molecular identification and characterization of light-absorption
      properties of BrC chromophores. Identification of BrC components is challenging
      due to the complexity of atmospheric aerosols. In this study, we employ two
      complementary ionization techniques, atmospheric pressure photo ionization (APPI)
      and electrospray ionization (ESI), to obtain broad coverage of both polar and
      nonpolar BrC components using high-resolution mass spectrometry (HRMS). These
      techniques are combined with chromatographic separation of BrC compounds with
      high performance liquid chromatography (HPLC), characterization of their light
      absorption with a photodiode array (PDA) detector, and chemical composition with
      HRMS. We demonstrate that this approach enables more comprehensive
      characterization of BrC in biomass burning organic aerosols (BBOAs) emitted from
      test burns of sage brush biofuel. In particular, we found that nonpolar BrC
      chromophores such as PAHs are only detected using positive mode APPI. Meanwhile,
      negative mode ESI results in detection of polar compounds such as nitroaromatics,
      aromatic acids, and phenols. For the BrC material examined in this study, over
      40% of the solvent-extractable BrC light absorption is attributed to water
      insoluble, nonpolar to semipolar compounds such as PAHs and their derivatives,
      which require APPI for their identification. In contrast, the polar, water
      soluble BrC compounds, which are detected in ESI, account for less than 30% of
      light absorption by BrC.

PMID- 30293423
TI  - Hyporheic Exchange Controls Fate of Trace Organic Compounds in an Urban Stream.
AB  - First-order half-lives for 26 trace organic compounds (TrOCs) were determined in
      the hyporheic zone (HZ) and along a 3 km reach of a first-order stream in South
      Australia during both dry and wet seasons. Two salt tracer experiments were
      conducted and evaluated using a transient storage model to characterize seasonal
      differences in stream residence time and transient storage. Lagrangian and time
      integrated surface water sampling were conducted to calculate half-lives in the
      surface water. Half-lives in the HZ were calculated using porewater samples
      obtained from a modified mini-point sampler and hyporheic residence times
      measured via active heat-pulse sensing. Half of the investigated TrOCs (e.g.,
      oxazepam, olmesartan, candesartan) were not significantly removed along both the
      investigated river stretch and the sampled hyporheic flow paths. The remaining
      TrOCs (e.g., metformin, guanylurea, valsartan) were found to be significantly
      removed in the HZ and along the river stretch with relative removals in the HZ
      correlating to reach-scale relative removals. Using the modeled transport
      parameters, it was estimated that wet season reach-scale removal of TrOCs was
      predominately caused by removal in the HZ when the intensity of hyporheic
      exchange was also higher. Factors that increase HZ exchange are thus likely to
      promote in-stream reactivity of TrOCs.

PMID- 30293424
TI  - A Correlated Series of Au/Ag Nanoclusters Revealing the Evolutionary Patterns of
      Asymmetric Ag Doping.
AB  - Doping of metal nanoclusters is an effective strategy for tailoring their
      functionalities for specific applications. To gain fundamental insight into the
      doping mechanism, it is of critical importance to have access to a series of
      correlated bimetal nanoclusters with different doping levels and further reveal
      the successive transformations. Herein, we report asymmetric doping of Ag into an
      Au21 nanocluster to form a series of new Au/Ag bimetal nanoclusters and the
      effects of doping on the evolution of size, structure, and properties based upon
      X-ray crystallography and optical spectroscopy analyses. The asymmetric doping
      discovered in the series reveals two important rules. First, the heteroatom
      doping-induced kernel transformation mechanism is revealed, explaining the
      successive conversions from Au21(S-Adm)15 with an incomplete cuboctahedral kernel
      to Au20Ag1(S-Adm)15 with a complete cuboctahedral Au12Ag1 kernel and then to
      Au19Ag4(S-Adm)15 with an icosahedral Au10Ag3 kernel. The electron density
      accumulated on the central Au atom(s) is rationalized to force an expansion of
      radial metal-metal bond angles, which triggers the cuboctahedral-to-icosahedral
      kernel conversion. This mechanism is generalized by elucidating several other
      cases. Second, through comparison of a series of seven nanoclusters (all
      protected by adamantanethiolate), we find that the unit cell symmetry of their
      crystals is correlated with the symmetry of the cluster's kernel. Specifically,
      we observe a sequential change from triclinic to monoclinic to trigonal unit cell
      in the series with increasing kernel symmetry. The kernel structure-dependent
      optical properties are also discussed.

PMID- 30293425
TI  - Low-Temperature Oxidation of Ethylene by Ozone in a Jet-Stirred Reactor.
AB  - Ethylene oxidation initiated by ozone addition (ozonolysis) is carried out in a
      jet-stirred reactor from 300 to 1000 K to explore the kinetic pathways relevant
      to low-temperature oxidation. The temperature dependencies of species' mole
      fractions are quantified using molecular-beam mass spectrometry with electron
      ionization and single-photon ionization employing tunable synchrotron-generated
      vacuum-ultraviolet radiation. Upon ozone addition, significant ethylene oxidation
      is found in the low-temperature regime from 300 to 600 K. Here, we provide new
      insights into the ethylene ozonolysis reaction network via identification and
      quantification of previously elusive intermediates by combining experimental
      photoionization energy scans and ab initio threshold energy calculations for
      isomer identification. Specifically, the C2H4 + O3 adduct C2H4O3 is identified as
      a keto-hydroperoxide (hydroperoxy-acetaldehyde, HOOCH2CHO) based on the
      calculated and experimentally observed ionization energy of 9.80 (+/-0.05) eV.
      Quantification using a photoionization cross-section of 5 Mb at 10.5 eV results
      in 5 ppm at atmospheric conditions, which decreases monotonically with
      temperature until 550 K. Other hydroperoxide species that contribute in larger
      amounts to the low-temperature oxidation of C2H4, like H2O2, CH3OOH, and C2H5OOH,
      are identified and their temperature-dependent mole fractions are reported. The
      experimental evidence for additional oxygenated species such as methanol, ketene,
      acetaldehyde, and hydroxy-acetaldehyde suggest multiple active oxidation routes.
      This experimental investigation closes the gap between ozonolysis at atmospheric
      and elevated temperature conditions and provides a database for future modeling.

PMID- 30293426
TI  - Trianglamine-Based Supramolecular Organic Framework with Permanent Intrinsic
      Porosity and Tunable Selectivity.
AB  - Here we introduce for the first time a metal-free trianglamine-based
      supramolecular organic framework, T-SOF-1, with permanent intrinsic porosity and
      high affinity to CO2. The capability of tuning the pore aperture dimensions is
      also demonstrated by molecular guest encapsulation to afford excellent CO2/CH4
      separation for natural gas upgrading.

PMID- 30293427
TI  - Exciton-Phonon Interactions Govern Charge-Transfer-State Dynamics in CdSe/CdTe
      Two-Dimensional Colloidal Heterostructures.
AB  - CdSe/CdTe core-crown type-II nanoplatelet heterostructures are two-dimensional
      semiconductors that have attracted interest for use in light-emitting
      technologies due to their ease of fabrication, outstanding emission yields, and
      tunable properties. Despite this, the exciton dynamics of these complex
      materials, and in particular how they are influenced by phonons, is not yet well
      understood. Here, we use a combination of femtosecond vibrational spectroscopy,
      temperature-resolved photoluminescence (PL), and temperature-dependent structural
      measurements to investigate CdSe/CdTe nanoplatelets with a thickness of four
      monolayers. We show that charge-transfer (CT) excitons across the CdSe/CdTe
      interface are formed on two distinct time scales: initially from an ultrafast
      (~70 fs) electron transfer and then on longer time scales (~5 ps) from the
      diffusion of domain excitons to the interface. We find that the CT excitons are
      influenced by an interfacial phonon mode at ~120 cm-1, which localizes them to
      the interface. Using low-temperature PL spectroscopy we reveal that this same
      phonon mode is the dominant mechanism in broadening the CT PL. On cooling to 4 K,
      the total PL quantum yield reaches close to unity, with an ~85% contribution from
      CT emission and the remainder from an emissive sub-band-gap state. At room
      temperature, incomplete diffusion of domain excitons to the interface and
      scattering between CT excitons and phonons limit the PL quantum yield to ~50%.
      Our results provide a detailed picture of the nature of exciton-phonon
      interactions at the interfaces of 2D heterostructures and explain both the broad
      shape of the CT PL spectrum and the origin of PL quantum yield losses.
      Furthermore, they suggest that to maximize the PL quantum yield both improved
      engineering of the interfacial crystal structure and diffusion of domain excitons
      to the interface, e.g., by altering the relative core/crown size, are required.

PMID- 30293429
TI  - Topological Characterization of Rigid-Nonrigid Transition across the Frenkel
      Line.
AB  - The dynamics of supercritical fluids, a state of matter beyond the gas-liquid
      critical point, changes from diffusive to oscillatory motions at high pressure.
      This transition is believed to occur across a locus of thermodynamic states
      called the Frenkel line. The Frenkel line has been extensively investigated from
      the viewpoint of the dynamics, but its structural meaning is still not well
      understood. This Letter interprets the mesoscopic picture of the Frenkel line
      entirely based on a topological and geometrical framework. This discovery makes
      it possible to understand the mechanism of rigid-nonrigid transition based not on
      the dynamics of individual atoms but on their instantaneous configurations. The
      topological classification method reveals that the percolation of solid-like
      structures occurs above the rigid-nonrigid crossover densities.

PMID- 30293428
TI  - In-Search Assignment of Monoisotopic Peaks Improves the Identification of Cross
      Linked Peptides.
AB  - Cross-linking/mass spectrometry has undergone a maturation process akin to
      standard proteomics by adapting key methods such as false discovery rate control
      and quantification. A poorly evaluated search setting in proteomics is the
      consideration of multiple (lighter) alternative values for the monoisotopic
      precursor mass to compensate for possible misassignments of the monoisotopic
      peak. Here, we show that monoisotopic peak assignment is a major weakness of
      current data handling approaches in cross-linking. Cross-linked peptides often
      have high precursor masses, which reduces the presence of the monoisotopic peak
      in the isotope envelope. Paired with generally low peak intensity, this generates
      a challenge that may not be completely solvable by precursor mass assignment
      routines. We therefore took an alternative route by '"in-search assignment of the
      monoisotopic peak" in the cross-link database search tool Xi (Xi-MPA), which
      considers multiple precursor masses during database search. We compare and
      evaluate the performance of established preprocessing workflows that partly
      correct the monoisotopic peak and Xi-MPA on three publicly available data sets.
      Xi-MPA always delivered the highest number of identifications with ~2 to 4-fold
      increase of PSMs without compromising identification accuracy as determined by
      FDR estimation and comparison to crystallographic models.

PMID- 30293430
TI  - Influence of the SPR Experimental Conditions on the G-Quadruplex DNA Recognition
      by Porphyrin Derivatives.
AB  - Surface plasmon resonance (SPR) is a powerful technique to study the interactions
      of ligands with analytes and therefore a number of biosensor surfaces and
      injection methods have been developed so far. However, many experimental
      parameters can affect the interactions and consequently the affinity
      measurements. In particular, the interactions of positively charged analytes
      (often used for anionic nucleic acids targets) can be influenced by the sensing
      surfaces (e.g., negatively charged), leading to significant nonspecific
      interactions as well as regeneration problems. The aim of the present work is to
      investigate the effect of different parameters, including ionic strength, SPR
      biosensor (i.e., nature of the surfaces), and the injection method on the
      recognition of porphyrin G-quadruplex ligands. We demonstrate that the injection
      method does not influence the affinity whereas the ionic strength and the nature
      of the surface impact the recognition properties of the porphyrin for the G
      quadruplex DNA. We also found that self-assembled monolayer coating surface
      presents many advantages in comparison with carboxymethylated dextran surface for
      SPR studies of G-quadruplex DNA/ligand interactions: (i) the electrostatic
      interaction with charged analytes is less important, (ii) its
      structure/composition is less sensitive to the ionic concentration and less prone
      to unspecific adsorption, (iii) it is easily homemade, and (iv) the cost is
      approximately 10 times cheaper.

PMID- 30293431
TI  - Polyelectrolyte Composite Membranes Containing Electrospun Ion-Exchange
      Nanofibers: Effect of Nanofiber Surface Charges on Ionic Transport.
AB  - Poly(vinyl alcohol) (PVA)-based ion-exchange nanofibers (IEX-NFs) and their
      composite polyelectrolyte membranes were prepared and characterized. The PVA
      based NFs are well dispersed and form a three-dimensional network structure in
      the polymer matrix, Nafion. All of the prepared membranes show a similar ion
      exchange capacity of ~1.0 mmol g-1. The ionic conductivities through the PVA- b
      PSS-NF/Nafion composite membranes are superior to that of the Nafion membranes,
      but the conductivity through the PVA-NF/Nafion composite membrane is half that of
      the Nafion membrane. Our electrokinetic measurements clearly indicate that a high
      density of ion-exchange groups on the NF surface results in a continuous ionic
      transport path in the polymer matrix. In addition, the mechanical strength of all
      of the NF-composite membranes is improved compared with that of the membranes
      without NF.

PMID- 30293432
TI  - Driving a Liquid Crystal Phase Transition Using a Photochromic Hydrazone.
AB  - The dynamic manipulation of the properties of soft matter can lead to adaptive
      functional materials that can be used in advanced applications. Here we report on
      a new chiral dopant, built on an isosorbide scaffold attached to two bistable
      hydrazone-based light switches that can be used to control the self-assembly, and
      hence photophysical properties, of nematic liquid crystals (LCs). The bistability
      of the switch allows kinetic trapping of various helical assemblies as a function
      of the photostationary states, resulting in the reflection of different
      wavelengths of light. Surprisingly, doping 5CB with the chiral switch, followed
      by irradiation with blue light, triggers an isothermal phase change from the
      helical cholesteric phase to the untwisted lamellar smectic A* phase. This
      transition was used to modulate the transparency of a LC film, resulting in a
      light-gated optical window.

PMID- 30293433
TI  - Development of a Highly Sensitive Direct Competitive Fluorescence Enzyme
      Immunoassay Based on a Nanobody-Alkaline Phosphatase Fusion Protein for Detection
      of 3-Phenoxybenzoic Acid in Urine.
AB  - 3-Phenoxybenzoic acid (3-PBA) is a human urinary metabolite of many pyrethroid
      insecticides and can be used as a biomarker to monitor human exposure to these
      pesticides. A rapid and sensitive direct competitive fluorescence enzyme
      immunoassay (dc-FEIA) for detecting 3-PBA on the basis of a nanobody (Nb)
      alkaline phosphatase (AP) fusion protein was developed. The anti-3-PBA Nb-AP
      fusion protein was expressed and purified. The 50% inhibitory concentration
      (IC50) and linear range of dc-FEIA were 0.082 and 0.015-0.447 ng/mL,
      respectively, with a detection limit of 0.011 ng/mL. The IC50 of dc-FEIA was
      improved by nearly ten times compared with those of one-step and three-step
      direct competitive enzyme-linked immunosorbent assay (dc-ELISA). Spiked urine
      samples were detected by both dc-FEIA and liquid chromatography-mass spectrometry
      (LC-MS), and the results showed good consistency between the two analysis
      methods, indicating the reliability of dc-FEIA based on the Nb-AP fusion protein
      for detecting 3-PBA in urine.

PMID- 30293434
TI  - Emanating Jets As Shaped by Surface Tension Forces.
AB  - We show that emanating jets can be regarded as growing liquid towers, which are
      shaped by the twofold action of surface tension: first the emanated fluid is
      being accelerated back by surface tension force, herewith creating the boundary
      conditions to solve the shape of the liquid tower as a solution of an equation
      mathematically related to the hydrostatic Young-Laplace equation, known to give
      solutions for the shape of pending and sessile droplets, and wherein the only
      relevant forces are gravity g and surface tension gamma. We explain that for an
      emanating jet under specific constraints all mass parts with density rho will
      experience a uniform time dependent acceleration a( t). An asymptotic solution is
      subsequently numerically derived by making the corresponding Young-Laplace type
      equation dimensionless and by dividing all lengths by a generalized time
      dependent capillary length lambdac( t) = [Formula: see text]. The time dependent
      surface tension gamma( t) can be derived by measuring both time dependent
      acceleration a( t) and time dependent capillary length lambdac( t). Jetting
      experiments with water and coffee show that the dynamic surface tension behavior
      according to the emanating jet method and with the well-known maximum bubble
      pressure method are the same, herewith verifying the proposed model.

PMID- 30293435
TI  - Keeping them interested: a national study of factors that change medical student
      interest in working rurally.
AB  - INTRODUCTION: In most countries it remains a challenge to sustain the rural
      medical workforce. Based on evidence that medical students with rural backgrounds
      are more likely than their urban peers to enter rural practice, medical schools
      may have rural entry pathways. It is less well established what happens to career
      intentions during medical school. This study assessed how rural intentions
      persist or change during medical school and sought factors associated with either
      persistence or change in rural intention. METHODS: Students who participate in
      the Medical Schools Outcomes Database and Longitudinal Tracking project complete
      surveys at entry to and exit from medical school. They are asked about
      demographics, career intentions and influencing factors. This study used data
      from students at both of New Zealand's medical schools from 2006 to 2016.
      Participants were placed into one of four groups: rural intention at entry and
      rural intention at exit (R-R), urban at entry and rural at exit (U-R), rural at
      entry and urban at exit (R-U) or urban at entry and urban at exit (U-U). 'Rural'
      was defined as an area with a population of 100 000 or fewer. Differences among
      the groups in demographics and influencing factors were analysed. RESULTS:
      Overall, 4368 students completed an entry survey (response rate 85.9%), and 2243
      students completed an exit survey (response rate 66.4%). A third intended to work
      in a rural area; of these, 49% had a rural background and 51% an urban
      background. From the linked entry and exit data (n=1114), there were 239 (21.4%),
      188 (16.8%), 135 (12.1%) and 552 (49.5%) students in the R-R, U-R, R-U and U-U
      groups respectively (p<0.001). Most students had a stable geographical career
      intention. Of those who changed, more moved towards a rural intention than away
      from it. Medical students with a persistent rural pattern had characteristics of
      a rural background (70%), being female (68%), New Zealand European (76%) or
      having involvement with a rural club for at least 1 year (45%). These students
      were also more likely to express a GP career intention as their first choice
      (25%). There were small differences in age, but otherwise no particular
      demographic factors were associated with students who changed intention.
      Similarly there were only small differences in perceived career influencing
      factors among groups. CONCLUSION: This large national study shows a stability of
      career location intention for the majority of students. It confirms earlier
      findings of the importance of rural background in rural career preference, but
      shows that women may have a higher propensity for a persisting rural interest.
      Apart from providing quality experience in rural areas for all students, and
      facilitating rural clubs, the study did not reveal any other strategies that
      might be used by medical schools to either increase or prevent the loss of rural
      interest.

PMID- 30293436
TI  - Reducing Telemetry Use Is Safe: A Retrospective Analysis of Rapid Response Team
      and Code Events After a Successful Intervention to Reduce Telemetry Use.
AB  - Interventions guiding appropriate telemetry utilization have successfully reduced
      use at many hospitals, but few studies have examined their possible adverse
      outcomes. The authors conducted a successful intervention to reduce telemetry use
      in 2013 on a hospitalist service using educational modules, routine review, and
      financial incentives. The association of reduced telemetry use with the incidence
      of rapid response team (RRT) and code activations was assessed in a retrospective
      cohort study of 210 patients who experienced a total of 233 RRT and code events
      on the inpatient internal medicine services from January 2012 through March 2015
      at a tertiary care center. The incidence of adverse events for the hospitalist
      service was not significantly different during the intervention and
      postintervention period as compared to the preintervention period. Reducing
      inappropriate telemetry use was not associated with an increase in the incidence
      rates of RRT and code events.

PMID- 30293437
TI  - Investigational drugs in phase II clinical trials for moderate to severe plaque
      psoriasis - potential new treatments on the horizon.
AB  - INTRODUCTION: Psoriasis is a common immune disorder for which there are many FDA
      approved therapies. Older oral drugs had limited efficacy and considerable side
      effects. Biologics have been a major advance but require self-administered
      injections, and many patients prefer oral options. Because many patients fear
      needles, oral drugs are a welcome option. This review provides an update on oral
      drugs in Phase II development for psoriasis. Areas covered: A literature review
      was performed to identify these drugs by using search terms such as 'psoriasis',
      'agents', 'drugs', and 'phase 2 development'. Baricitinib and KDO 25 are the oral
      drugs that appear to hold the most promise due to the balance they maintain
      between efficacy and adverse effects. If a RORgammat inhibitor can be identified
      that has no hepatotoxicity, then that may be the most promising new oral
      treatment. Expert opinion: Several new oral psoriasis medications are currently
      being investigated. One major challenge remains medication cost and insurance
      coverage. Phase III studies are needed to determine efficacy and safety in large
      cohorts of psoriasis patients. An increase in the number of approved oral
      medications for psoriasis would mean more choice for psoriasis patients.

PMID- 30293438
TI  - Synthesis of natural product inulavosin via Ga(OTf)3-Catalyzed Hetero Diels-Alder
      Dimerization of salicyl alcohol derivative.
AB  - Inulavosin, a natural melanogenesis inhibitor, has been synthesized smoothly from
      readily available and inexpensive starting materials by using a Ga(OTf)3
      catalyzed room temperature hetero Diels-Alder dimerization of salicyl alcohol
      derivative and a regioselective phenol monobromination as the key steps.

PMID- 30293439
TI  - Rituximab Exhibits Altered Pharmacokinetics in Patients With Membranous
      Nephropathy.
AB  - BACKGROUND: Rituximab (RTX) is a chimeric monoclonal anti-CD20 antibody used off
      label in the treatment of membranous nephropathy (MN). Unfortunately, limited
      information is available on the pharmacokinetics of therapeutic proteins such as
      RTX in patients with glomerular kidney diseases. OBJECTIVE: The current study
      evaluated RTX pharmacokinetics in patients with MN (n = 20) who received 4 RTX
      weekly intravenous infusions (375 mg/m2) over a month, with a repeat of the
      identical treatment at 6 months. Baseline patient characteristics were gender (17
      male/3 female), age (49 +/- 13 years), and body surface area (2.2 +/- 0.24 m2).
      METHODS: Compartmental pharmacokinetic analyses were conducted using Phoenix, and
      comparisons of these parameters were made between the MN patients and published
      data from 2 reference populations without kidney diseases (follicular lymphoma
      and autoimmune disorders). RESULTS: Patients with MN exhibited a shorter half
      life, reduced volume of central compartment, decreased area under the serum
      concentration-time curve (exposure), and increased RTX clearance from the central
      compartment versus previous reports in the reference patient populations.
      CONCLUSIONS AND RELEVANCE: These results suggest that shorter half-life and lower
      exposures to RTX in patients with MN may necessitate higher doses and/or changes
      to dosing frequency to optimize the relationships between serum concentrations
      and therapeutic effects.

PMID- 30293440
TI  - A Chinese cross-sectional study on depression and anxiety symptoms in patients
      with psoriasis vulgaris.
AB  - Previous studies have reported a higher incidence of depression and anxiety in
      psoriasis patients compared to the general population, which has important
      implications for assessment and treatment. In this study, we determined the
      frequency of depression and anxiety in Chinese patients with psoriasis and its
      relationship with disease severity and other demographic variables. The study
      included 208 Chinese patients with psoriasis vulgaris. The Patient Health
      Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7) were used to
      screen for depression and anxiety. The Psoriasis Area and Severity Index (PASI)
      was used to assess the severity of psoriasis. Of the 208 patients included in the
      study, 29 patients (13.9%) were positive for moderate-to-severe depression (PHQ-9
      >= 10) and 22 patients (10.6%) were positive for anxiety (GAD-7 >= 10) symptoms.
      Both positive stress reactors who perceived stress as an exacerbating factor of
      psoriasis and moderate-to-severe psoriasis were found to be positive predictors
      for the presence of moderate-to-severe depression or anxiety symptoms while
      longer duration and late onset age played a protective role. In the sample of
      Chinese patients with psoriasis there was a clinically significant prevalence of
      depression and anxiety. Our study suggests that Chinese psoriasis patients should
      be screened for psychiatric comorbidities.

PMID- 30293441
TI  - Risk factors for antenatal anxiety: A systematic review of the literature.
AB  - BACKGROUND: Given the prevalence of antenatal anxiety and its consistent
      associations with adverse pregnancy and child outcomes, early detection and
      management of anxiety are essential. OBJECTIVE: The aim was to identify risk
      factors for anxiety among pregnant women by systematically reviewing original
      research. METHODS: Cross-sectional, case-control and cohort studies that examined
      associations between antenatal anxiety and at least one potential risk factor
      prospectively or retrospectively and measured anxiety independent from other
      mental health conditions were included. Studies rated strong/moderate in
      methodological quality appraisal were used to synthesise the evidence. RESULTS:
      Factors associated with greater risk of anxiety included previous pregnancy loss,
      medical complications, childhood abuse, intimate partner violence,
      denial/acceptance coping styles, personality traits, inadequate social support,
      history of mental health problems, high perceived stress and adverse life events.
      CONCLUSIONS: Several risk factors identified in this review are detectable in
      routine prenatal care visits (e.g. previous pregnancy loss, pregnancy
      complications), potentially modifiable (e.g. coping styles, social support,
      partner factors) and can be identified prior to pregnancy (e.g. psychosocial
      factors), underlining the significance of pre-conception mental health screening.

PMID- 30293443
TI  - Landscapes of tomorrow: Precision psychiatry and beyond.

PMID- 30293442
TI  - Psychiatry trainee welfare - from words to action.
AB  - OBJECTIVE: To review selected literature available on trainee welfare and reflect
      on our own experiences to provide practical advice to our colleagues and suggest
      strategies to enhance trainee welfare. CONCLUSIONS: Promoting the welfare of
      psychiatry trainees requires a three-pronged approach. We must care for ourselves
      through individual strategies; we must advocate for optimization of the systems
      we work in to minimize modifiable factors associated with burnout; and we must
      continue on the perennial challenge of culture change to reduce stigma around
      stress and mental illness and promote a healthier workplace.

PMID- 30293444
TI  - Giving G a Meaning: An Application of the Bifactor-(S-1) Approach to Realize a
      More Symptom-Oriented Modeling of the Beck Depression Inventory-II.
AB  - The Beck Depression Inventory-II is one of the most frequently used scales to
      assess depressive burden. Despite many psychometric evaluations, its factor
      structure is still a topic of debate. An increasing number of articles using
      fully symmetrical bifactor models have been published recently. However, they all
      produce anomalous results, which lead to psychometric and interpretational
      difficulties. To avoid anomalous results, the bifactor-(S-1) approach has
      recently been proposed as alternative for fitting bifactor structures. The
      current article compares the applicability of fully symmetrical bifactor models
      and symptom-oriented bifactor-(S-1) and first-order confirmatory factor analysis
      models in a large clinical sample ( N = 3,279) of adults. The results suggest
      that bifactor-(S-1) models are preferable when bifactor structures are of
      interest, since they reduce problematic results observed in fully symmetrical
      bifactor models and give the G factor an unambiguous meaning. Otherwise, symptom
      oriented first-order confirmatory factor analysis models present a reasonable
      alternative.

PMID- 30293445
TI  - Convergent, Discriminant, and Concurrent Validity of Nonmemory-Based Performance
      Validity Tests.
AB  - To supplement memory-based Performance Validity Tests (PVTs) in identifying
      noncredible performance, we examined the validity of the two most commonly used
      nonmemory-based PVTs-Dot Counting Test (DCT) and Wechsler Adult Intelligence
      Scale-Fourth edition (WAIS-IV) Reliable Digit Span (RDS)-as well as two
      alternative WAIS-IV Digit Span (DS) subtest PVTs. Examinees completed DCT, WAIS
      IV DS, and the following criterion PVTs: Test of Memory Malingering, Word Memory
      Test, and Word Choice Test. Validity groups were determined by passing 3 (valid;
      n = 69) or failing ?2 (noncredible; n = 30) criterion PVTs. DCT, RDS, RDS-Revised
      (RDS-R), and WAIS-IV DS Age-Corrected Scaled Score (ACSS) were significantly
      correlated (but uncorrelated with memory-based PVTs). Combining RDS, RDS-R, and
      ACSS with DCT improved classification accuracy (particularly for DCT/ACSS) for
      detecting noncredible performance among valid-unimpaired, but largely not valid
      impaired examinees. Combining DCT with ACSS may uniquely assess and best
      supplement memory-based PVTs to identify noncredible neuropsychological test
      performance in cognitively unimpaired examinees.

PMID- 30293446
TI  - How secure are the secure psychiatric units in New South Wales?
AB  - OBJECTIVES: To evaluate the therapeutic security characteristics of the secure
      forensic mental health inpatient units in New South Wales, Australia. METHODS:
      This study evaluated all eight secure inpatient units in New South Wales using a
      validated tool, the Security Needs Assessment Profile. RESULTS: A pattern of
      decreasing therapeutic security across the secure units was found, consistent
      with their intended security levels, from high security through to open security.
      However, important inconsistencies across and between levels of security were
      highlighted. CONCLUSIONS: This study clarifies the therapeutic security structure
      of the New South Wales forensic mental health service, which is an essential
      first step in service development and reform.

PMID- 30293447
TI  - The mutagenic effect of psychostimulant modafinil in Wistar rats in vivo.
AB  - The demands imposed by today's world require a fast and efficient society, then,
      significant section of the population looks for support from psychotropic
      medicine. Modafinil is a psychostimulant that promotes wakefulness, it being
      recommended for treatment of narcolepsy, obstructive sleep apnea, and shift-work
      sleep disorder, besides being a cognitive function potentiator. However, chemical
      components of drugs can alter genetic material. Thus, the present study evaluated
      the cytotoxic and clastogenic/mutagenic potential of 0.25, 0.50, and 0.75 mg of
      Modafinil/mL of corn oil/100g body weight in acute treatments and subacute
      treatments, 15 days, to Rattus norvegicus, treated via gavage in a single daily
      dose. The drug was not cytotoxic at any of the evaluated doses in either of the
      treatments. However, the medicine showed clastogenic/mutagenic activity in the
      acute treatment group at the standard dose and at double dose. Data from the
      present study indicates that there should be greater caution as to the use of
      this psychostimulant by human beings.

PMID- 30293448
TI  - Alosetron versus traditional pharmacotherapy in clinical practice: effects on
      resource use, health-related quality of life, safety and symptom improvement in
      women with severe diarrhea-predominant irritable bowel syndrome.
AB  - OBJECTIVE: Severe diarrhea-predominant irritable bowel syndrome (IBS-D) is
      associated with decreased health-related quality of life (HRQOL) and increased
      health care costs. Treatment recommendations for IBS-D often start with
      traditional pharmacotherapy (TP), with escalation to alosetron, rifaximin or
      eluxadoline if there is no success. There has been no previous head-to-head
      clinical trial comparing IBS-D treatment outcome for alosetron versus TP. This
      study, GSK protocol S3B30020, evaluated resource use, work productivity, health
      related quality of life and global symptom response in women with IBS-D who were
      treated with alosetron or TP. METHODS: A total of 1956 patients who met criteria
      for severe IBS-D were randomized to treatment with alosetron 1 mg twice daily
      (BID) or only TP for up to 24 weeks. Work productivity and resource use were
      evaluated by standard questionnaires, HRQOL by the IBSQOL instrument and IBS
      symptoms by the Global Improvement Scale (GIS). RESULTS: Compared to only TP,
      alosetron-treated patients reported: (1) fewer clinic/office visits for any
      health problem (p = .0181) or for IBS-D (p = .0004); (2) reduced use of over-the
      counter medications for IBS-D (p < .0001); (3) fewer days of lost work
      productivity (p < .0001); (4) decreased restriction of social and outdoor
      activities (p < .0001); and (5) greater global improvement in IBS-D symptoms (p <
      .0001). Alosetron treatment improved HRQOL scores for all domains (p < .0001).
      Incidence of adverse events during alosetron use was not remarkable and was
      similar to that previously reported. CONCLUSIONS: Alosetron 1 mg BID
      significantly reduced health care utilization and lost productivity, and
      significantly improved global IBS symptoms, HRQOL, and participation in outdoor
      and social activities compared with treatment response to TP.

PMID- 30293449
TI  - Extended-release morphine sulfate and naltrexone hydrochloride (EMBEDA):
      naltrexone-associated withdrawal and abuse-related effects in patients with
      chronic pain and recreational opioid users.
AB  - OBJECTIVE: To review the effects of naltrexone on withdrawal-related adverse
      events (AEs) and euphoria-related effects, and the relationship between plasma
      naltrexone concentrations and withdrawal across EMBEDA (MSN; extended-release
      morphine sulfate with sequestered naltrexone) studies. METHODS: Five studies in
      pain patients and a safety review summarizing AE reports during the first year
      following approval of MSN were assessed for withdrawal reports. Three of these
      studies also assessed Clinical Opiate Withdrawal Scale (COWS) scores. Plasma
      naltrexone concentrations of MSN-treated individuals were summarized. Abuse
      potential was assessed in four studies in non-dependent recreational opioid
      users. RESULTS: Withdrawal AEs occurred in 13/1781 patients across five MSN
      studies, and 25/182 cases involving withdrawal were reported in the safety
      review. In three of these studies, 11/964 patients experienced moderate
      withdrawal (COWS score = 13-24) and 1/964 patients experienced moderately severe
      withdrawal (score = 28); all were either non-compliant with study drug, had
      undetectable plasma naltrexone concentrations, or were tapering to placebo. In
      >=89% of plasma naltrexone concentration samples from patients who took MSN (n =
      166), naltrexone was below the limit of quantification (4.0 pg/mL). In four
      studies with non-dependent recreational opioid users (n = 118), crushed MSN was
      associated with significantly lower scores of drug liking, high, and take drug
      again than crushed morphine sulfate (p <= 0.005). CONCLUSIONS: When taken intact
      as directed, naltrexone in MSN does not precipitate withdrawal. However, when MSN
      is crushed, naltrexone mitigates, but does not eliminate, the euphorigenic
      effects of crushed morphine sulfate.

PMID- 30293450
TI  - Butea monosperma (Lam.) Taub. Bark fractions protect against free radicals and
      induce apoptosis in MCF-7 breast cancer cells via cell-cycle arrest and ROS
      mediated pathway.
AB  - Butea monosperma (Lam.) Taub. is an ethnomedicinal tree of remedial value in the
      treatment of diabetes, bone fractures, and liver and neurological disorders.
      However, the information available on DNA-protective and anti-proliferative
      potential of bark of this tree is scarce. In the present study, the
      extract/fractions obtained from bark of B. monosperma were evaluated for
      antioxidant, DNA-protective, and anti-proliferative activities, along with their
      phytochemical profiling for identifying major constituents present in them.
      Different extract/fractions, namely, Bmth (methanol), Bhex (hexane), Bchl
      (chloroform), and Beac (ethyl acetate), were prepared and evaluated for
      antioxidant activity using in vitro assays. Extract/fractions were also evaluated
      for anti-proliferative and apoptotic activity in human breast carcinoma cell line
      MCF-7, using in vitro assays, namely, MTT, clonogenic, and neutral comet assay,
      along with confocal microscopy and flow cytometry. Among all extract/fractions, a
      pronounced antioxidant activity was exhibited by Bchl and Beac fractions, in
      DPPH. (EC50 213.2 and 161.5 ug/mL, respectively), ABTS+. (EC50 139.3 and 44.1
      ug/mL, respectively), and reducing power assay (EC50 86.7 and 84.5 ug/mL,
      respectively). Both fractions protected plasmid DNA against hydroxyl radical
      induced damage in plasmid nicking assay. Bchl and Beac were also observed to
      inhibit the growth of MCF-7 cells (GI50 203.7 and 246.5 ug/mL, respectively).
      Both fractions induced apoptosis in MCF-7 cells, by arresting the cell cycle in
      G1 and sub-G1 phase, respectively, enhancing ROS levels, decreasing mitochondrial
      membrane potential, and inducing double-strand DNA breaks. HPLC analysis revealed
      high kaempferol content in Bchl, and catechin, epicatechin, and gallic acid in
      Beac.

PMID- 30293451
TI  - Assessment of Bony Subfibular Impingement in Flatfoot Patients Using Weight
      Bearing CT Scans.
AB  - BACKGROUND:: Lateral hindfoot pain in patients with flatfoot deformity is
      frequently attributed to subfibular impingement. It remains unclear whether this
      is primarily due to bony or soft-tissue impingement. No studies have used weight
      bearing CT scans to evaluate subfibular impingement. METHODS:: Patients with
      posterior tibial tendonitis were retrospectively searched and reviewed. Subjects
      had documented flatfoot deformity, posterior tibial tenderness, weight-bearing
      plain radiographs, and a weight-bearing CT scan. CT scans were evaluated for
      calcaneofibular impingement on the coronal view and talocalcaneal impingement on
      the sagittal view. The distance between these structures was measured, along with
      the sinus tarsi volume. In the second part of this study, 6 normal volunteers
      underwent weight-bearing CT scans on a platform that held both feet in 20 degrees
      of varus, followed by 20 degrees of valgus. The same measurements were performed.
      RESULTS:: Thirty-five percent of flatfoot patients with posterior tibial
      tendonitis had bony impingement between the fibula and calcaneus on the coronal
      view. Thirty-eight percent had bony impingement between the talus and calcaneus
      on the sagittal view. Subjects with bony impingement based on CT scan had
      significantly higher talonavicular abduction angles on plain radiographs than
      those without impingement. Sinus tarsi volume decreased by more than half when
      the subtalar joint moved from varus to valgus in normal controls. CONCLUSION::
      Bony subfibular impingement in patients with flatfeet was less common than
      previously reported. Accurate diagnosis of bony impingement may be useful for
      surgical decision-making. LEVEL OF EVIDENCE:: Level III, retrospective
      comparative study.

PMID- 30293452
TI  - Five alternative splicing variants of the TYR gene and their different roles in
      melanogenesis in the Muchuan black-boned chicken.
AB  - 1. The TYR gene encodes tyrosinase, a multifunctional enzyme that is essential
      for melanin biosynthesis in melanocytes. This experiment involved the cloning and
      characterisation of the TYR gene in chicken. Five alternative splice variants
      were identified in the black feather bulb and designated as TYR-AS1, TYR-AS2, TYR
      AS3, TYR-AS4 and TYR-AS5. 2. Among the 11 chicken tissues examined, the feather
      bulb, comb and skin showed higher levels of all TYR variants. All TYR variants
      were expressed at significantly different levels in black and white feather bulbs
      (P < 0.05) and may be involved in melanin formation in plumage. Only TYR-AS1,
      which plays an important role in muscle melanogenesis, was significantly
      differentially expressed between black and white muscle (P < 0.01). All TYR
      variants were expressed at significantly different levels in black and white skin
      (P < 0.01). 3. The mRNA expression levels of the 5 variants were closely
      associated with skin melanogenesis in the chicken. These findings provide new
      clues to the molecular mechanism of melanin formation in the Muchuan black-boned
      chicken.

PMID- 30293453
TI  - Pancreatic islet dysfunction in type 2 diabetes mellitus.
AB  - Islet dysfunction is a hallmark of type 2 diabetes mellitus (T2DM). Compelling
      evidence suggests that accumulation of islet amyloid in the islets of Langerhans
      significantly contribute to beta-cell dysfunction and diabetes. Emerging evidence
      implicates a role for cystic fibrosis transmembrane-conductance regulator in the
      regulation of insulin secretion from pancreatic islets. Impaired first-phase
      insulin responses and glucose homeostasis have also been reported in cystic
      fibrosis patients. The transforming growth factor-beta protein superfamily is
      central regulators of pancreatic cell function, and has a key role in pancreas
      development and pancreatic disease, including diabetes and islet dysfunction. It
      is also becoming clear that islet inflammation plays a key role in the
      development of islet dysfunction. Inflammatory changes, including accumulation of
      macrophages, have been documented in type 2 diabetic islets. Islet dysfunction
      leads to hyperglycemia and ultimately the development of diabetes. In this
      review, we describe these risk factors and their associations with islet
      dysfunction.

PMID- 30293454
TI  - No gold medals: Assessing Australia's international mental health performance.
AB  - OBJECTIVE: The objective of this study was to present an assessment of
      Australia's mental health system performance, within its social context, by
      comparison with other countries. METHOD: A review of existing literature and
      databases from both Australia and overseas was undertaken. Systems permitting
      international comparison of mental health and its social context are few. The
      review is limited in scope. RESULTS: Although Australia was one of the first
      nations to develop and adopt a national mental health policy (in 1992), the data
      that are available suggest that we are not World leaders across the identified
      domains. CONCLUSIONS: While international benchmarking can play an important role
      in fostering quality improvement, there are only limited mental health or social
      system performance data sources to utilise. It would be desirable for a more
      systematic international process to be established to review existing approaches
      and design a new multilateral strategy. It would be important that this new
      strategy reflected the full experience of mental health and its broader social
      context.

PMID- 30293455
TI  - Intensive suicide prevention: Provide Intensive Contact and Start 2
      antidepressants.

PMID- 30293456
TI  - Value of perceived support on depressive symptoms and hazardous drinking among
      underserved HIV+ adults 50 and older.
AB  - The current study examined the association between perceived social support,
      depressive symptoms and alcohol use among people living with HIV (PLWH) 50 and
      older who identified as Black. Participants included 96 men and women ages 50 and
      older. Participants completed an interviewer-administered assessment examining
      mental and behavioral health functioning. Mediation analyses examined whether
      perceived support mediated the association between depressive symptoms and
      hazardous drinking. Depressive symptoms were significantly associated with
      hazardous drinking (B = .068, SE = .035, t = 1.92, p = 0.05) and negatively
      associated with having the desired amount of contact with a primary supporter (B
      = -.072, SE = .018, z = -3.96, p < 0.001). In addition, having the desired amount
      of contact with a confidant was negatively associated with hazardous drinking (B
      = -.543, SE = .208, t = -2.61, p 0 < .01). The effect of depressive symptoms on
      hazardous drinking when controlling for having adequate contact with a primary
      supporter was not significant (B = .033, SE = .04, t = .829, p = 0.41). Having a
      valued confidant mediated the association between depressive symptoms and
      hazardous drinking. Thus, social support interventions may be an effective method
      of reducing hazardous drinking among older PLWH.

PMID- 30293457
TI  - The effects of vest type dynamic elastomeric fabric orthosis on sitting balance
      and gross manual dexterity in children with cerebral palsy: a single-blinded
      randomised controlled study.
AB  - PURPOSE: To evaluate the effects of vest type dynamic elastomeric fabric orthosis
      on posture and balance during sitting and gross manual dexterity and to compare
      the efficacy of daily wearing time of 2 h versus 6 h. METHOD: Twenty-four
      children with cerebral palsy (CP) aged 3-9 years with GMFCS levels III and IV
      were randomised to either of three groups: (i) a control group who received only
      conventional exercise therapy, (ii) dynamic elastomeric fabric orthosis 2 h group
      who wore the orthosis for 2 h during therapy and dynamic elastomeric fabric
      orthosis 6 h group who wore the orthosis for 4 h in addition to the 2 h of wear
      along with therapy during hospital inpatient stay for 2 weeks. Children continued
      to use dynamic elastomeric fabric orthosis during the post-discharge period. The
      primary outcome measure was the Sitting Assessment Scale. The secondary outcome
      measurements were the sitting dimension of Gross Motor Function Measure, Box and
      Block Test and Parent Satisfaction Survey. Assessments were made before
      treatment, at post-treatment, at 1-month post-treatment, and at 3-months post
      treatment. Sitting Assessment Scale and Box and Block Test were also assessed
      when immediately after wearing the orthosis. This trial is registered with
      Clinicaltrials.gov, under number NCT03191552. RESULTS: All groups showed similar
      improvements except the control group which showed less improvement in Sitting
      Assessment Scale scores compared to the dynamic elastomeric fabric orthosis
      groups. Dynamic elastomeric fabric orthosis groups showed greater improvements
      compared to the control group in the Sitting Assessment Scale but not in the
      sitting dimension of Gross Motor Function Measure and Box and Block Test at post
      treatment, at 1-month post-treatment and at 3-months post-treatment. When the
      dynamic elastomeric fabric orthosis groups (2 h versus 6 h) were compared, there
      were no significant differences in any of the assessments. The Sitting Assessment
      Scale and Box and Block Test scores also improved immediately after the patients
      put on the orthosis. At 1-month post-treatment, parents of children in the
      control group reported less satisfaction than parents of the children in dynamic
      elastomeric fabric orthosis groups. CONCLUSIONS: Dynamic elastomeric fabric
      orthosis vest has an immediate effect on the sitting balance and gross manual
      dexterity. It also provides improvements in posture and balance during sitting.
      Wearing dynamic elastomeric fabric orthosis vest for 2 h during therapy is as
      much effective as wearing it for 6 h in children with CP in addition to therapy
      to improve sitting balance. Implications for rehabilitation Dynamic elastomeric
      fabric orthosis vest provides improvements in sitting balance when used in
      addition to conventional therapy in children with cerebral palsy. Wearing dynamic
      elastomeric fabric orthosis for 2 h and wearing dynamic elastomeric fabric
      orthosis vest for 6 h resulted in similar clinical outcomes. Dynamic elastomeric
      fabric orthosis vest has an immediate effect on sitting balance and gross manual
      dexterity in children with cerebral palsy.

PMID- 30293458
TI  - An exercise program for people with severe peripheral neuropathy and diabetic
      foot ulcers - a case series on feasibility and safety.
AB  - PURPOSE: To examine a non-weightbearing exercise program for persons with severe
      peripheral neuropathy (PN) and a diabetic foot ulcer in terms of feasibility and
      safety. MATERIALS AND METHODS: Five men (mean (SD) age of 68.2 (7.1) years) with
      diabetes, severe peripheral neuropathy and an active foot ulcer, participated in
      a 10-week exercise program. Program adherence, patient satisfaction, healing of
      foot ulcers, adverse advents, ability to perform activities of daily life, and
      changes in muscle strength were assessed. RESULTS: All participants completed the
      program with a session attendance from 85 to 95%, and with high satisfaction (>=9
      points on a 10-point numeric rating scale). Only minor adverse events occurred,
      and ulcers were reduced for all participants, from a median of 1.9 (IQR, 1.1-7.3)
      cm2 to 0.0 (0.0-3.0) cm2. The distance on stationary bike was improved from a
      mean (SD) of 3.30 (1.1) to 5.36 (0.5) kilometers, and strength training loads
      were progressed. Ability to perform in self-selected activities of daily living
      improved from a median of 4.3 (2-5) to 6.7 (5-8) on the Patient Specific
      Functional Scale (0-10 points), while maximal isometric knee-extension muscle
      strength improved with 23%. CONCLUSIONS: A non-weightbearing exercise program for
      people with diabetes, severe peripheral neuropathy and foot ulcers seems feasible
      and safe. Further studies are needed to confirm these findings. Implications for
      rehabilitation An exercise program designed for people with severe peripheral
      neuropathy and diabetic foot ulcers can be safe by means of not compromising
      healing of foot ulcers. Feasible in terms of attendance and progression. An
      alternative to passive waiting for ulcer to heal in a population already
      deconditioned.

PMID- 30293459
TI  - Why it's time to focus on masculinity in mental health training and clinical
      practice.
AB  - OBJECTIVE: Men present with complex, diverse and often contradictory expressions
      of masculinity that are relevant to their health status. This article argues for
      the inclusion of masculinity into mental health curricula in Australia.
      Masculinity mediates health outcomes by influencing help seeking and engagement
      with treatment. CONCLUSION: An online curricula audit of publicly available
      information from Australian medical programs and their professional bodies
      reveals increasing awareness of the needs, but limited practical inclusion of
      masculinity models in training and practice. Described are the elements essential
      to training and subsequent clinical practice to curb the poor mental health
      outcomes of Australian men.

PMID- 30293460
TI  - Corrigendum.

PMID- 30293461
TI  - Design, synthesis, and biological evaluation of novel iso-flavones derivatives as
      H3R antagonists.
AB  - Histamine H3 receptor (H3R), a kind of G-protein coupled receptor (GPCR), is
      expressed mainly in the central nervous system (CNS) and plays a vital role in
      homoeostatic control. This study describes the design and synthesis of a series
      of novel H3R antagonists based on the iso-flavone scaffold. The results of the
      bioactivity evaluation show that four compounds (1c, 2c, 2h, and 2o) possess
      significant H3R inhibitory activities. Molecular docking indicates that a salt
      bridge, pi-pi T-shape interactions, and hydrophobic interaction all contribute to
      the interaction between compound 2h and H3R.

PMID- 30293462
TI  - Interleukin-6 measured using the automated electrochemiluminescence immunoassay
      method for the identification of intra-amniotic inflammation in preterm prelabor
      rupture of membranes.
AB  - INTRODUCTION: We aimed to compare the amniotic fluid interleukin (IL)-6
      concentrations measured using the automated electrochemiluminescence immunoassay
      method and ELISA, and to establish an IL-6 concentration cut-off value for intra
      amniotic inflammation (IAI) in preterm prelabor rupture of membranes (PPROM),
      which can be used in the automated electrochemiluminescence immunoassay method.
      MATERIALS AND METHODS: A total of 120 women with PPROM were included in this
      study. Amniotic fluid samples were obtained via transabdominal amniocentesis. IL
      6 concentrations were assessed using both the automated electrochemiluminescence
      immunoassay method and ELISA, the current gold standard. IAI was defined as an
      amniotic fluid IL-6 concentration of >= 2600 pg/mL measured using ELISA. RESULTS:
      A correlation between both assays was found (Spearman's rho = 0.97; p < 0.0001).
      Based on the receiver-operating characteristic curve for the identification of
      IAI (area under the curve = 0.99), a cut-off value of >= 3000 pg/mL was selected
      for the automated electrochemiluminescence immunoassay method with a sensitivity
      of 88%, specificity of 99%, positive predictive value of 97%, negative predictive
      value of 96%, and likelihood ratio of 76.

PMID- 30293463
TI  - Auditory brainstem response in full-term neonates born to mothers with iron
      deficiency anemia: relation to disease severity.
AB  - BACKGROUND: Iron is crucial for fetal brain development; however, there are
      insufficient data regarding the effects of maternal iron deficiency anemia (IDA)
      on auditory neural maturation. AIM: We evaluated the effect of maternal IDA on
      auditory brainstem response (ABR) in full-term neonates. METHODS: Out of 223
      pregnant women, 50 were diagnosed as having IDA and 50 healthy mothers were
      enrolled as controls. ABR test was done for the studied neonates within 48 hours
      after birth and at 3 months. RESULTS: We found that hemoglobin and iron profile
      were lower in neonates born to anemic mothers compared with controls. Of 100
      neonates screened for ABR, 25 failed the test (all of them were born to anemic
      mothers). The majority of neonates who failed the screening ABR test (88%) had
      latent iron deficiency (cord blood ferritin 11-75 ug/L). After 3 months, 85
      neonates underwent diagnostic ABR test which revealed significantly prolonged
      interpeak latencies I-III, III-V, and I-V among neonates born to IDA mothers
      compared with the control group. Within the IDA group, all interpeak latencies
      were more prolonged in neonates with latent iron deficiency and in those born to
      mothers with serum ferritin <15 ug/L. Logistic regression analysis showed that
      maternal hemoglobin and mean corpuscular volume could predict neonatal ABR
      results. CONCLUSIONS: IDA during late pregnancy adversely affects cord blood iron
      and hearing status. ABR results are closely related to the severity of maternal
      and neonatal iron status. Antenatal screening of pregnant mothers is needed to
      improve fetal iron status and prevent abnormal auditory maturation.

PMID- 30293465
TI  - Local recurrence of brain metastasis reduced by intra-operative hyperthermia
      treatment.
AB  - PURPOSE: Brain metastasis is a common complication in cancer patients. Local
      recurrence after total resection of metastatic brain tumor has been frequently
      reported. In this study, we developed a new hyperthermia device and applied it to
      metastatic brain tumor patients intra-operatively to study if hyperthermia
      treatment could reduce local tumor recurrence. MATERIALS AND METHODS: A total of
      63 metastatic brain patients were enrolled in the study with an informed consent
      obtained from every patient. After total resection of the tumor, the hyperthermia
      device was applied intra-operatively to the resection cavity. The surrounding
      brain tissue at 5 mm in depth from the tumor resection margin was raised to 42.5 
      degrees C for a total of 60 minutes (Clinical Research Information Service
      Registration Number: KCT0001308). RESULTS: A total of 10 local recurrences were
      observed in 63 patients who received hyperthermia treatment showing a local
      recurrence rate of 15.8%. It was significantly lower than the local recurrence
      rate of those who received conventional treatment (34%) when analyzed with one
      tailed z-test (p value: .001). Kaplan-Meier analysis also showed a significantly
      lower recurrence rate in the hyperthermia treatment group (p value: .0003).
      Complications included two cases of seizures and two cases of wound infection.
      CONCLUSIONS: Results of this study suggest that intra-operative hyperthermia
      treatment after total resection of metastatic brain tumor could reduce local
      recurrence of tumor. We believe that intra-operative hyperthermia treatment could
      be used as an adjuvant therapy to surgery and post-operative radiotherapy, or as
      a salvage treatment in patients who cannot receive further radiotherapy.

PMID- 30293464
TI  - A clinically oriented computer model for radiofrequency ablation of hepatic
      tissue with internally cooled wet electrode.
AB  - PURPOSE: To improve the computer modelling of radiofrequency ablation (RFA) by
      internally cooled wet (ICW) electrodes with added clinically oriented features.
      METHODS: An improved RFA computer model by ICW electrode included: (1) a
      realistic spatial distribution of the infused saline, and (2) different domains
      to distinguish between healthy tissue, saline-infused tumour, and non-infused
      tumour, under the assumption that infused saline is retained within the tumour
      boundary. A realistic saline spatial distribution was obtained from an in vivo
      pig liver study. The computer results were analysed in terms of impedance
      evolution and coagulation zone (CZ) size, and were compared to the results of
      clinical trials conducted on 17 patients with the same ICW electrode. RESULTS:
      The new features added to the model provided computer results that matched well
      with the clinical results. No roll-offs occurred during the 4-min ablation. CZ
      transversal diameter (4.10 +/- 0.19 cm) was similar to the computed diameter
      (4.16 cm). Including the tumour and saline infusion in the model involved (1) a
      reduction of the initial impedance by 10 - 20 Omega, (2) a delay in roll-off of
      20 s and 70 - 100 s, respectively, and (3) 18 - 31% and 22 - 36% larger CZ size,
      respectively. The saline spatial distribution geometry was also seen to affect
      roll-off delay and CZ size. CONCLUSIONS: Using a three-compartment model and a
      realistic saline spatial distribution notably improves the match with the outcome
      of the clinical trials.

PMID- 30293466
TI  - The direct and indirect costs of epilepsy in Poland estimates for 2014-2016
      years.
AB  - BACKGROUND: According to the current data, around 1% of the Poland population
      have epilepsy, which comprises about 400,000 people. This group of patients
      requires life-long therapy including both drug therapy and hospitalization. The
      character of the epilepsy has a significant impact on the expenses borne by
      individual patients, and the prevalence of the disease has a significant impact
      on the health care system. METHODS: This article aims to measure the direct and
      indirect costs of epilepsy in Poland estimates for the years 2014-2016 (top-down
      approach). We use a modified human capital approach and a unique dataset provided
      by the number of Polish institutions including National Health Fund, Social
      Insurance Institution, and Central Statistical Office. RESULTS: Epilepsy burden
      in Poland is significant. In the years 2014-2016, the total direct cost of
      epilepsy amounted to, respectively, 355 mln PLN (84 mln EUR), 368 mln PLN (87 mln
      EUR), and 373 mln PLN (88 mln EUR), but the total indirect cost amounted to 1 bn
      PLN (239 mln EUR), 949 mln PLN (224 mln EUR), and 848 mln PLN (200 mln EUR).
      CONCLUSIONS: Direct and indirect costs of epilepsy can be a useful input for
      health technology analyses of drugs or economic impact assessments of public
      health programs.

PMID- 30293467
TI  - Analgesic effect of preoperative dezocine-based local anesthesia in patients
      undergoing inguinal hernia repair.
AB  - Objective This study was performed to investigate the analgesic effects of
      intramuscular injection of dezocine-based local anesthesia in patients undergoing
      inguinal hernia repair. Methods A total of 120 patients underwent local
      herniorrhaphy from July 2015 to December 2016 and were randomly divided into 2
      groups: the dezocine group, in which a preoperative intramuscular injection of
      dezocine was administered, and the control group, in which no dezocine injection
      was administered. The patients' pain and comfort levels were evaluated at 30
      minutes, 2 hours, 6 hours, 12 hours, and 24 hours postoperatively. Results The
      visual analog scale scores at 30 minutes, 2 hours, 6 hours, 12 hours, and 24
      hours were significantly lower in the dezocine than control group. In the
      Bruggemann comfort scale evaluation, patients who received dezocine injections
      showed significantly greater comfort than those in the control group at 30
      minutes, 2 hours, 6 hours, 12 hours, and 24 hours. No adverse reactions occurred
      in the dezocine group. Conclusions Dezocine-based local anesthesia can attenuate
      postoperative pain and increase the comfort level during and after herniorrhaphy.

PMID- 30293469
TI  - Making the most of lecture recordings; a student's perspective.

PMID- 30293468
TI  - Impact of oocyte donation on obstetric and perinatal complications in twin
      pregnancies.
AB  - AIM: To evaluate obstetric and perinatal outcomes of twin pregnancies obtained
      after in vitro fertilization with donated oocytes. METHODS: This is a case
      control study comparing 50 women with twin pregnancies after oocyte donation (OD)
      and 50 women after in vitro fertilization with autologous oocytes. Clinical
      records were reviewed and obstetric and perinatal outcome variables including
      rates of preeclampsia, gestational diabetes, pregnancy-induced hypertension,
      preterm delivery, premature rupture of membranes, cesarean delivery, birth
      weight, Apgar score, pH test were compared. RESULTS: Women in the OD group were
      significantly older than those in the AO group (mean 40.8 versus 36 years old, p
      < .001). There were a higher risk of preeclampsia (OD 24% versus AO 8%), cesarean
      delivery (OD 90% versus AO 66%), and preterm birth before 37 weeks (OD 52% versus
      AO 32%). After adjustment for maternal age, only the risk of preterm birth
      remained significantly higher (OR 3.2 (1.15-8.86); p = .025). Comparing neonatal
      outcomes, there were no differences in birth weight, pH or Apgar score at birth.
      CONCLUSIONS: Twin pregnancies after OD are associated with a higher risk of
      preterm birth before 37 weeks of gestation. However, this did not translate into
      increased rate of adverse perinatal outcomes.

PMID- 30293470
TI  - Risk factors related to unnecessary emergency medical services transport for
      pediatric patients.
AB  - Objectives This study evaluated unnecessary emergency medical services (EMS)
      transport for pediatric patients depending on whether they received emergency
      department (ED) treatment after EMS transport. Methods Pediatric patients were
      divided into two groups according to whether they received treatment at the ED
      (ED treatment) or did not receive treatment at the ED (non-ED treatment). Results
      The non-ED treatment group comprised 65 of the total 794 patients. The elapsed
      time from scene to arrival at the ED was longer in the non-ED treatment group
      than in the ED treatment group. Weekdays as the days of EMS transport, ground
      falls rather than traffic accidents as the reason for non-disease-related
      symptoms, and no immobilization for prehospital treatment were risk factors for
      non-ED treatment in EMS-transported patients. Causes of not receiving ED
      treatment for the non-ED treatment group were the patient's or caregiver's
      decision (12%) and the doctor's suggestion (88%). Conclusions Weekdays rather
      than weekends, ground falls rather than traffic accidents, and no immobilization
      before hospital are risk factors for not receiving ED treatment. The most common
      cause of not receiving ED treatment is the doctor's suggestion.

PMID- 30293471
TI  - Stability of plasma proteins and factors in Chinese universal pooled plasma.
AB  - Objective This study aimed to determine the precision dose of Chinese universal
      pooled plasma (CUPP) developed by our laboratory, and the stability of plasma
      proteins and factors. Methods A total of 100 single fresh-frozen plasma (FFP)
      units were selected to test plasma proteins, including total protein, albumin,
      fibrinogen, factor V, factor VIII, antithrombin-III, and protein C. Different
      pooling protocols with 20, 40, 60, 80, and 100 units were used to optimize the
      number of pooled units. The pooled plasma was then used to further evaluate the
      optimal storage conditions and duration at 22 degrees C, 4 degrees C, and -20
      degrees C. Results There were considerable differences in plasma protein levels
      among single units of FFP. After different pooling protocols, the mean value of
      plasma proteins did not significantly change. However, with a larger number of
      pooled samples, plasma proteins were more stable with a smaller standard
      deviation. Acceptable storage for CUPP was achieved with storage for 1 day at 22
      degrees C, 4 days at 4 degrees C, and 3 months at -20 degrees C. Conclusion A
      uniform level of plasma proteins and factors in CUPP appears to support
      establishment of a precise dose of plasma.

PMID- 30293472
TI  - Associations between socioeconomic status, atrial fibrillation, and outcomes: a
      systematic review.
AB  - BACKGROUND: Atrial fibrillation (AF) is a growing epidemic and evidence of a
      relationship to socioeconomic status (SES) is inconsistent. We aimed to summarize
      the literature about SES and AF and defined two objectives: (1) To examine the
      association between SES and the risk of AF; (2) To examine the association
      between SES and AF-related outcomes in an AF-population. METHODS: We performed a
      separate search for each objective in Ovid-MEDLINE and Ovid-Embase. For objective
      1, the population included was healthy participants and outcome of interest was
      AF. For objective 2, the population included were patients with AF and outcome of
      interest was mortality, treatment, ablation for AF, knowledge about AF, and
      morbidity. RESULTS: For objective 1, 12 studies were included. No consistent
      pattern for an association between SES and the risk of AF was discovered. For
      objective 2, 39 studies comprising 42 outcomes were included. The majority of
      studies showed an association between low SES and increased mortality and
      morbidity. CONCLUSION: Low SES was associated with poorer outcomes when AF was
      present. These findings may imply that health-care professionals and policy
      interventions should focus on the promotion of AF-education and management among
      patients with AF and low SES.

PMID- 30293473
TI  - Prostate shape significantly affects the HoLEP procedure time and energy usage: A
      retrospective pilot study.
AB  - INTRODUCTION: In this study we evaluate the influence of longitudinal and
      transverse length of prostate size measured on the magnetic resonance imaging
      (MRI) scan on the overall outcomes of HoLEP. MATERIAL AND METHODS: The patients
      were divided into two groups based on the shape of the prostate. Group 1 had a
      longitudinal shape with a longitudinal diameter greater than the transverse
      diameter, whereas group 2 had an oval shape with a transverse diameter greater
      than the longitudinal diameter. The pre-operative, peri-operative and the one
      month post-operative data along with the urinary parameters were then evaluated.
      RESULTS: The two groups were comparable with regard to their pre-operative
      values. While the median lobe enucleation time and morcellation time showed no
      difference, group 1 showed a significantly shorter (p < 0.01) operative time for
      lateral lobe enucleation, lower laser energy usage and better enucleation
      efficiency. However, there was no difference in the median lobe enucleation time,
      morcellation time, haemoglobin drop, duration of urethral catheterization and
      hospital stay. The groups were also comparable with regard to the improvement in
      urinary parameters and complications. CONCLUSION: Prostate shape plays a
      significant role in the surgical treatment of BPH.

PMID- 30293474
TI  - Changes of arterial pressure following relief of obstruction in adults with
      hydronephrosis.
AB  - BACKGROUND: As much as 20% of all cases of hypertension are associated with
      kidney malfunctions. We have previously demonstrated in animals and in pediatric
      patients that hydronephrosis causes hypertension, which was attenuated by
      surgical relief of the ureteropelvic junction (UPJ) obstruction. This
      retrospective cohort study aimed to investigate: (1) the proposed link between
      hydronephrosis, due to UPJ obstruction, and elevated arterial pressure in adults;
      and (2) if elevated blood pressure in patients with hydronephrosis might be
      another indication for surgery. MATERIALS AND METHODS: Medical records of 212
      patients undergoing surgical management of hydronephrosis, due to UPJ
      obstruction, between 2000 and 2016 were assessed. After excluding patients with
      confounding conditions and treatments, paired arterial pressures (i.e.
      before/after surgery) were compared in 49 patients (35 years old; 95% CI 29-39).
      Split renal function was evaluated by using mercaptoacetyltriglycine (MAG3)
      renography before surgical management of the hydronephrotic kidney. RESULTS:
      Systolic (-11 mmHg; 95% CI 6-15 mmHg), diastolic (-8 mmHg; 95% CI 4-11 mmHg), and
      mean arterial (-9 mmHg; 95% CI 6-12) pressures were significantly reduced after
      relief of the obstruction (p < 0.001). Split renal function of the hydronephrotic
      kidney was 39% (95% CI 37-41). No correlations were found between MAG3 and blood
      pressure level before surgery or between MAG3 and the reduction of blood pressure
      after surgical management of the UPJ obstruction. CONCLUSIONS: In adults with
      hydronephrosis, blood pressure was reduced following relief of the obstruction.
      Our findings suggest that elevated arterial pressure should be taken into account
      as an indication to surgically correct hydronephrosis.

PMID- 30293475
TI  - A standardised database of Chinese emotional film clips.
AB  - Film clips are widely used in emotion research due to their relatively high
      ecological validity. Although researchers have established various film clip sets
      for different cultures, the few that exist related to Chinese culture do not
      adequately address positive emotions. The main purposes of the present study were
      to establish a standardised database of Chinese emotional film clips that could
      elicit more categories of reported positive emotions compared to the existing
      databases and to expand the available film clips that can be used as neutral
      materials. Two experiments were conducted to construct the database. In
      experiment 1, 111 film clips were selected from more than one thousand Chinese
      movies for preliminary screening. After 315 participants viewed and evaluated
      these film clips, 39 excerpts were selected for further validation. In experiment
      2, 147 participants watched and rated these 39 film clips, as well as another 8
      excerpts chosen from the existing databases, to compare their validity.
      Eventually, 22 film excerpts that successfully evoked three positive emotions
      (joy, amusement, and tenderness), four negative emotions (moral disgust, anger,
      fear, and sadness), and neutrality formed the standardised database of Chinese
      emotional film clips.

PMID- 30293476
TI  - A case report of TB versus idiopathic granulomatous mastitis with erythema
      nodosum, reactive arthritis, cough, and headache.
AB  - Tuberculous mastitis (TBM) is relatively rare disease with an incidence ranging
      between 0.1 and 4%. Most of the cases are culture negative and often mistaken
      with chronic benign idiopathic granulomatous mastitis (IGM). It is very crucial
      to distinguish culture negative TBM from other causes of mastitis as the
      treatment differs tremendously. We describe here in a young woman originally from
      India and residing in Qatar; a non endemic area of tuberculosis; for more then
      fifteen years. She presented with 2 months history of right breast mass, followed
      by low grade fever, dry cough, headache, erythema nodosum, arthritis, and
      arthralgia. In view of the origin of the patient, positive family history for
      tuberculosis and positive quantiferon, the patient was started empirically on
      anti-tuberculous treatment (ATT). One week later she developed paradoxical
      reaction to ATT. This case illustrates unusual and rare manifestations of primary
      TBM and highlights the importance of differentiating and treating culture
      negative TBM from IGM.

PMID- 30293478
TI  - Examining Validity of the Print Tool Compared With Test of Handwriting Skills
      Revised.
AB  - Handwriting assessments offer practitioners an objective measure to determine
      handwriting deficits, track student progress, and provide evidence for the use of
      occupational therapy intervention. This study determines the concurrent validity
      of the Print Tool with the Test of Handwriting Skills-Revised (THS-R) and
      examines the alignment of teacher perception with the Print Tool. Participants
      included 46 first- and second-grade students. All participants completed both
      handwriting assessments, and classroom teachers ( n = 4) rated each students'
      overall handwriting performance and potential areas of concern addressed by the
      Print Tool. The Print Tool overall scores have a strong correlation ( r = .606)
      with THS-R standard scores, suggesting good concurrent validity. Median Print
      Tool overall scores increased with each successive teacher rating classification,
      supporting alignment with teacher perception. This study provides preliminary
      evidence for the use of the Print Tool by occupational therapy practitioners to
      identify potential handwriting deficits that also align with teacher perception
      of performance.

PMID- 30293477
TI  - Words in larger font are perceived as more important: explaining the belief that
      font size affects memory.
AB  - Words presented in larger font size are considered more memorable and rated with
      higher judgments of learning (JOLs). One explanation for this phenomenon is that
      people believe that font size affects memory. However, it is not clear why people
      hold this belief. One alternative is that font size represents importance, with
      larger fonts implying more relevant information. More important information is
      judged as more memorable and is, in fact, better remembered. In Experiments 1 and
      2 we presented words in small (18 points) and extra-large font (250 points) and
      found higher JOLs and higher judgments of importance with extra-large fonts. A
      mediation analysis showed that importance accounted for 21-23% of the effect of
      font size on JOLs. In Experiment 3, we tested whether processing fluency was
      higher with the extra-large font. In a lexical decision task, participants were
      slower at detecting words and non-words with extra-large than small font, which
      is the opposite of what the processing fluency hypothesis predicts. This result
      shows that the font-size effect persists even in conditions in which perceived
      fluency should be lower. In sum, this research explained the belief that font
      size affects memory because words in larger fonts are considered more important.

PMID- 30293479
TI  - Negev Bedouin Teachers' Attitudes Toward ADHD and Its Pharmacological Treatment.
AB  - Little is known about the attitudes of Negev Bedouin toward attention
      deficit/hyperactivity disorder (ADHD) and its pharmacological treatment. This
      study examines the perspectives of Negev Bedouin teachers on pharmacological
      treatment. Thirty-six teachers are asked to consider how their views influence
      the way they relate to pupils' parents. A grounded-theory analysis of
      semistructured interviews illuminates ambivalence in teachers' attitudes.
      Teachers, like the rest of their community, when asked about the implications of
      an ADHD evaluation for their children, respond that ADHD and its pharmacological
      treatment cause dishonor. When asked what ADHD means when it is their pupils who
      are diagnosed and treated, however, teachers, like the education establishment,
      accept the need for medication. However, they fail to communicate this need to
      parents because their attempts to do so show parents that they consider their
      children "flawed"-causing parents to oppose treatment even more lest they succumb
      to social stigma.

PMID- 30293480
TI  - How Funerals Accomplish Family: Findings From a Mass-Observation Study.
AB  - The article analyses how potentially conflicting frames of grief and family
      operate in a number of English funerals. The data come from the 2010 Mass
      Observation directive "Going to Funerals" which asked its panel of correspondents
      to write about the most recent funeral they had attended. In their writings,
      grief is displayed through conventional understandings of family. Drawing on
      Randall Collins, we show how the funeral stratifies mourners into family or
      nonfamily, a stratification accomplished-by family and nonfamily-through both
      outward display and inner feeling. The funerals described were more about a very
      traditional notion of family than about grief; family trumped grief, or at least
      provided the frame through which grief could be written about; and perceptions of
      "family" prompted emotions which in turn defined family. The funerals were
      portrayed as a distinct arena privileging family over the fluid and varied
      personal attachments highlighted in both the new sociology of personal life and
      in the concept of disenfranchised grief.

PMID- 30293481
TI  - Niraparib - A promising drug with hematological toxicity.
AB  - Ovarian cancer is the second most common and the most lethal gynecological
      malignancy in the western world. Unfortunately, there are lack of methods for
      early screening and diagnosis of the disease. Because of this, most of the cases
      are diagnosed at an advanced stage and have poor prognosis. The standard
      treatment of ovarian cancer is maximal cytoreductive surgical debulking followed
      by platinum-based chemotherapy. There are new molecular agents available for
      maintenance therapy of ovarian cancer including anti-angiogenic therapies, poly
      adenosine diphosphate ribose polymerase inhibitors, inhibitors of growth factor
      signaling, or folate receptor inhibitors, as well as several immunotherapeutic
      approaches. Niraparib is a poly adenosine diphosphate ribose polymerase inhibitor
      that has shown to be clinically effective as maintenance therapy in patients with
      platinum sensitive, recurrent ovarian cancer. Studies have shown the median
      duration of progression-free survival was significantly longer among those
      receiving niraparib than among those receiving placebo, regardless of presence or
      absence of BRCA gene mutations or homologous recombination deficiency status.
      Studies have shown that treatment-emergent Grade 3 or Grade 4 hematological
      events were observed in patients receiving niraparib including thrombocytopenia
      (33.8%), anemia (25.3%) and neutropenia (19.6%). Most of the hematological
      laboratory abnormalities occurred within the first three treatment cycles. After
      dose adjustment, the incidence of hematological abnormalities was infrequent
      beyond cycle 3. We are reporting two cases of Grade III/IV neutropenia and
      thrombocytopenia in patients treated with niraparib in our institution.
      Unfortunately, one of the patients succumbed to septic shock secondary to right
      lower lobe pneumonia while severely neutropenic. The second patient's blood
      counts improved after discontinuing the medication and with supportive
      transfusions during the hospitalization.

PMID- 30293482
TI  - Attribution of intentions and context processing in psychometric schizotypy.
AB  - INTRODUCTION: Impairment in Theory of mind (TOM) has frequently been associated
      with schizophrenia and with schizotypy. Studies have found that a tendency to
      over-attribute intentions and special meaning to events and to people is related
      to positive psychotic symptoms. Further, it has been suggested that this
      intentionality bias may be due to a broader deficit in context processing (CP).
      The aim of the present study was thus to investigate the relationship between
      positive schizotypy and both over-attribution of intentions and contextual
      processing. METHODS: One-hundred and nineteen healthy individuals completed the
      Schizotypal Personality Questionnaire and were assessed with tasks measuring
      contextual treatment and ToM. RESULTS: Results revealed that positive schizotypy
      was significantly related to an over-attribution of intentions on the ToM task
      and with a faster processing of implicit context. Partial correlational analyses
      indicated that the association between the attribution of intentions and positive
      schizotypy was not explained by a deficit of CP. In contrast, stepwise multiple
      regression analyses showed that both an over-attribution of intentions and a
      faster processing of implicit context significantly predicted positive
      schizotypy. CONCLUSIONS: These results show that an over-attribution of intention
      is independent from a broader deficit in context information processing and that
      they both possibly contribute to the development and maintenance of positive
      psychotic symptoms.

PMID- 30293484
TI  - Multiscale molecular interactions of tendon.

PMID- 30293483
TI  - Young Muslim Pakistani Women's Lived Experiences of Izzat, Mental Health, and
      Well-Being.
AB  - This article explores how six Pakistani Muslim women interpret cultural concepts
      of izzat (honor and self-respect); what role, if any, it has in their lives; and
      whether there is interplay between upholding izzat and the participants' help
      seeking strategies for mental health and well-being. Semistructured interviews
      were conducted and analyzed with an interpretative phenomenological analytic
      framework. Three themes were identified: (a) "the rules of izzat," (b)
      "negotiating tensions," and (c) "speaking out/breaking the 'rules.'" Findings
      highlighted new insights into the understanding of izzat and the implications
      these cultural concepts have for strategies in managing or silencing of
      psychological distress. Interviews illustrated tensions the participants
      experience when considering izzat, how these are negotiated to enable them to
      self-manage or seek help, and possible life experiences that might lead to self
      harm and attempted suicide. Notably, cultural codes, in particular izzat, appear
      to vary over the life course and are influenced by migration.

PMID- 30293485
TI  - What's ours is yours: recall of history for lesser-known countries is guided by
      one's own national history.
AB  - The present studies examine how people recall history. Sometimes, certain
      national histories are well known and sometimes they are not. We propose that,
      under certain circumstances, culturally distinctive representations of typical
      national histories can be used to guide recall, particularly in cases where the
      history is not well known. We focus on three national samples with varied levels
      of knowledge about each history: Great Britain, India, and the United States. In
      Study 1, we establish typical historical event templates for each nation
      consisting of events that a large proportion of participants from each sample
      identify as important in a typical nation's history. We examine points of
      divergence between the different groups' typical event templates and the valences
      of these events. In Study 2, we test and find that, in conditions of less
      knowledge, participants tend to refer to particular historical events that
      coincide with events unique to their own group's typical history. In Study 3, we
      demonstrate that this effect can be found even when a group possesses a
      reasonable amount of knowledge about the target country. We conclude by
      discussing the implications in relation to how such a retrieval strategy might
      inform interpretations of events in the present.

PMID- 30293486
TI  - Correlation of imaging and intraoperative findings in Pott's puffy tumour.
AB  - Introduction Pott's puffy tumour is characterised by frontal bone osteomyelitis
      accompanied by subperiosteal abscess. It can be further complicated by
      intracranial extension of the infectious process. Case presentation A 12-year-old
      boy initially presented with signs and imaging findings of pan-sinusitis. Despite
      antibiotic therapy, there was progressive swelling of the forehead region.
      Subsequent imaging studies revealed osteomyelitis of frontal bone, subcutaneous
      abscess and extension into intracranial space. The abscesses were surgically
      drained, and craniectomy for osteomyelitis was carried out. Conclusion The
      initial symptoms of Pott's puffy tumour can be subtle, and antibiotic use may
      mask the underlying sinister involvement of intracranial structures. Imaging
      plays an important role both in diagnosis and detection of possible intracranial
      complications.

PMID- 30293487
TI  - Living Arrangements, Offspring Migration, and Health of Older Adults in Rural
      China: Revelation From Biomarkers and Propensity Score Analysis.
AB  - OBJECTIVE: We examine the combined effects of living arrangements and
      outmigration of adult children on rural older adults' health profiles, measured
      by biomarker data from the China Health and Retirement Longitudinal Study 2011.
      METHOD: We employ biomarker data and propensity score analysis which allows us to
      effectively deal with selection issues that are commonly observed in the
      literature. RESULTS: We show complex health implications of living arrangements
      and offspring migration. Living in a traditional multigenerational household has
      limited health benefits to older adults. However, older parents of migrants who
      live in a multigenerational household have better fitness in blood pressure.
      Their advantage over parents of migrants in other living arrangements suggests
      added benefits of the presence of grandchildren. DISCUSSION: This study bridges
      the living arrangement and migration literature on health by showing that health
      effects of adult children's migration on older adults are contingent upon their
      living arrangements.

PMID- 30293489
TI  - Translation and validation of the Chinese version of the Cancer Stigma Scale.
AB  - Purpose To test the reliability and validity of the Chinese version of the Cancer
      Stigma Scale (CASS). Methods After translation, back-translation and cross
      cultural adaptation of the CASS into Chinese (C-CASS), a random online survey of
      the general population in China was conducted. Reliability was analyzed by
      internal consistency (Cronbach's alpha) and construct validity was analyzed by
      confirmatory factor analysis. The C-CASS was evaluated in a sample of 382 non
      cancer patients through online format. Results The study found that the C-CASS
      had satisfactory internal reliability (Cronbach's alpha of the overall scale and
      six components was 0.88 and 0.70-0.89, respectively). Confirmatory factor
      analysis confirmed the six-factor structure (chi2/df = 2.2, GFI = 0.91, CFI =
      0.94, RMSEA = 0.056, SRMR = 0.065). Younger individuals and those who had less
      knowledge of cancer showed more negative attitudes towards cancer. Conclusion The
      C-CASS had adequate internal consistency, reliability and indices of model fit,
      allowing its feasible use to assess levels of cancer stigma in Chinese
      populations.

PMID- 30293488
TI  - Anti-NMDA receptor encephalitis presenting as isolated aphasia in an adult.
AB  - Anti-NMDA receptor (NMDA-r) encephalitis is a relatively rare cause of autoimmune
      encephalitis with divergent clinical presentations. We report a case of an adult
      patient with anti-NMDA-r encephalitis presenting with isolated, abrupt-onset
      aphasia. Her condition remained unaltered over a period of 6 months. The
      patients' electroencephalogram findings were typical for NMDA-r encephalitis;
      however, her magnetic resonance imaging and cerebrospinal fluid analysis were
      normal. She responded well to immunotherapy, and aphasia eventually resolved. The
      natural course of the present case contradicts the rapidly progressive nature of
      typical NMDA-r encephalitis. Furthermore, it broadens the clinical spectrum of
      anti-NMDA-r encephalitis, to incorporate isolated, nonprogressive aphasia.

PMID- 30293490
TI  - Adaptive non-inferiority margins under observable non-constancy.
AB  - A central assumption in the design and conduct of non-inferiority trials is that
      the active-control therapy will have the same degree of effectiveness in the
      planned non-inferiority trial as in the prior placebo-controlled trials used to
      define the non-inferiority margin. This is referred to as the 'constancy'
      assumption. If the constancy assumption fails, decisions based on the chosen non
      inferiority margin may be incorrect, and the study runs the risk of approving an
      inferior product or failing to approve a beneficial product. The constancy
      assumption cannot be validated in a trial without a placebo arm, and it is
      unlikely ever to be met completely. When there are strong, observable predictors
      of constancy, such as dosing and adherence to the active-control product, we can
      specify conditions where the constancy assumption will likely fail. We propose a
      method for using measurable predictors of active-control effectiveness to specify
      non-inferiority margins targeted to the planned study population characteristics.
      We describe a pre-specified method, using baseline characteristics or post
      baseline predictors in the active-control arm, to adapt the non-inferiority
      margin at the end of the study if constancy is violated. Adaptive margins can
      help adjust for constancy violations that will inevitably occur in real clinical
      trials, while maintaining pre-specified levels of Type I error and power.

PMID- 30293491
TI  - The elderly as a target for obesity treatment.
AB  - The prevalence of obesity is increasing in the elderly population. The primary
      goal of obesity therapy in elderly is the improvement of metabolic complications
      and the prevention of severe functional limitations. Clinical studies could
      demonstrate that the combination of nutritional intervention and physical
      exercise is of advantage to improve the functional status. Study evidence about
      the efficacy and safety of medication for weight reduction in elderly is limited,
      and the risks of bariatric surgery outweigh the possible benefits. The test
      battery of the comprehensive geriatric assessment is an important tool to
      determine body composition, nutritional status as well as functional and
      cognitive capacities of the elderly patient. These results are of central
      importance for the treatment plan and goals.

PMID- 30293492
TI  - PEGylated insulin Lispro (LY2605541): clinical overview of a new long-acting
      basal insulin analog in the treatment of Type 2 diabetes mellitus.
AB  - Neutral Protamine Hagedorn insulin with an intermediate action profile has been
      in use for many years for the treatment of Type 1 diabetes and as an option for
      Type 2 diabetes. It is efficacious in reducing blood sugars, but shows
      substantial variability and risk of hypoglycemia. Basal insulin analogs have been
      developed in recent years to overcome these issues. Three basal insulin analogs
      are currently in the market in Europe. PEGylated insulin lispro is a new second
      generation basal insulin analog which most likely will undergo review in 2016 by
      the US FDA and EMA in Europe for possible approval for marketing. Phase III
      trials are finalized, but not yet published. Phase II studies suggest
      antiglycemic efficacy, possible with a preferential hepato-specific action, a low
      rate of hypoglycemia, minor weight loss and acceptable tolerability. The benefit
      risk profile needs, however, to be established.

PMID- 30293493
TI  - Anti-inflammatory effects of gastric bypass surgery and their association with
      improvement in metabolic profile.
AB  - Obesity is associated with chronic inflammation and metabolic disease. Bariatric
      surgery offers a treatment that can effectively reduce weight and improve the
      metabolic function. However, the effect of bariatric surgery on chronic
      inflammation in obesity is under-investigated. In this expert review, the authors
      outline the effect of Roux-en-Y gastric bypass, the most commonly performed
      bariatric surgery in current practice, on the markers of inflammation. They
      include a discussion of the relationship between inflammation and weight loss
      after surgery, the interaction between these markers and metabolic disease, and
      the effect on adipose tissue inflammation. They also briefly explore the role of
      glucagon-like-peptide 1 in remediating inflammation and the changes in gut
      microbiota after Roux-en-Y gastric bypass, and how they may be important in
      inflammation.

PMID- 30293494
TI  - Polemics of pioglitazone: an appraisal in 2015.
AB  - Pioglitazone is an inexpensive and effective oral drug for the treatment of Type
      2 diabetes. It addresses insulin resistance, one of the core pathophysiological
      defects in Type 2 diabetes, at both the adipose tissue and skeletal muscle level.
      As a majority of Type 2 diabetics classically exhibit higher insulin resistance,
      pioglitazone may strike exactly at the Achilles heel in this core pathogenesis.
      However, with the emerging association of bladder cancer with pioglitazone,
      French and German regulators were the first to ban or restrict pioglitazone use
      in 2011. The Indian regulators also suspended pioglitazone, although this ban was
      revoked within a month. Recently, a 10-year longitudinal study commissioned by US
      FDA found no association between bladder cancer and pioglitazone. Nevertheless,
      this controversy created a huge outcry in the medical fraternity. This review
      article is an overview of the development of this topic and an attempt to provide
      perspective on this contemporary issue.

PMID- 30293495
TI  - Reducing diabetic limb amputations in developing countries.
AB  - Among all the diabetes complications, diabetic foot complications are associated
      with the highest morbidity and mortality. Across the globe, 40-60% of all lower
      extremity non-traumatic amputations are performed in patients with diabetes. The
      most important intervention in reducing diabetic limb amputation in developing
      countries is the education of patients about proper limb care. Cost-effective
      education should be targeted for both healthcare workers and patients. One of
      these programs is the Step by Step Foot Project, which was piloted and carried
      out in Tanzania and India. In this review, the author explores the feasible ways
      of reducing diabetic limb amputation which can be achieved through a trained
      diabetes workforce working in an effective system of care that focuses on the
      education of both the healthcare provider and the patient.

PMID- 30293496
TI  - Guiding diabetes screening and prevention: rationale, recommendations and
      remaining challenges.
AB  - Advances made in diabetes management are not sufficient to reduce morbidity,
      mortality and cost without making prevention efforts at various levels imperative
      for substantial impact. Research has demonstrated the efficacy of lifestyle
      intervention and medications in preventing type 2 diabetes among diverse high
      risk groups commonly identified with oral glucose tolerance testing. Efficacy,
      sustainability and safety data are most comprehensive for lifestyle and
      metformin, with other medications also demonstrating efficacy and potential in
      the pharmacoprevention of diabetes. Subsequent implementation studies have
      demonstrated feasibility of lifestyle intervention programs at health centers,
      communities, and at local and national government levels. Challenges remain in
      widespread translation and reaching and engaging at-risk individuals and
      populations.

PMID- 30293497
TI  - Utility of sentinel lymph node biopsy for thyroid cancer: a comprehensive review.
AB  - Sentinel lymph node biopsy (SLNB) is a minimally invasive lymphatic mapping
      technique, used to identify lymph node micrometastases and stage multiple cancer
      types. Despite the performance of SLNB for thyroid cancer having been under study
      since 1998, its role has remained controversial. The objective of this review is
      to summarize current research reporting on SLNB for thyroid cancer, focusing on
      recent studies of its application to differentiated thyroid cancer. The technique
      and potential benefits of SLNB are reviewed with regards to its ability to
      identify lymph node metastases, aid in cancer prognostication, and direct
      surgical and medical treatment.

PMID- 30293498
TI  - Linagliptin/metformin HCl (fixed combination therapy) for the treatment of Type 2
      diabetes mellitus.
AB  - By the year 2030, diabetes mellitus will globally become the seventh leading
      cause of death. Currently, 382 million individuals worldwide have diabetes
      mellitus, with 80% residing in low- and middle-income countries. At present, Type
      2 diabetes mellitus (T2DM) accounts for 85-95% of the diabetes burden in high
      income countries. Alarmingly, this figure may be higher in the low- and middle
      income nations. In an effort to combat this silent but deadly disease,
      pharmaceutical manufacturers have developed a host of different agents, each
      targeting a specific biochemical pathway. Among the most recent additions to this
      armament is linagliptin/metformin HCl, a fixed combination therapy compound
      manufactured by Boehringer Ingelheim. This novel formulation combines metformin,
      an insulin sensitizer, with linagliptin, a dipeptidyl peptidase-4 enzyme
      inhibitor. This review will discuss the pharmacokinetic properties of this
      molecule, assess clinical efficacy and gauge its place in the treatment algorithm
      for T2DM.

PMID- 30293499
TI  - The role of genetic screening in medullary thyroid cancer: a clinician's view on
      the recent ATA guidelines.
AB  - The American Thyroid Association recently released its revised guidelines on the
      management of medullary thyroid carcinoma. This editorial highlights the American
      Thyroid Association recommendations on genetic screening for medullary thyroid
      carcinoma and briefly discusses the future perspectives from the clinician's
      standpoint.

PMID- 30293500
TI  - Local recurrence of papillary thyroid cancer.
AB  - Management of advanced papillary thyroid cancer (PTC >10 mm) is changing its
      focus. Mortality was the main outcome measure for patients treated before the
      90s. In the past two decades, however, most patients diagnosed with PTC belong to
      the very low risk of death group. On the other hand, local recurrence of PTC
      remains a clinical problem, with rates up to 25% depending on the presence of
      nodal metastasis, tumor diameter, and the skill of the surgeon to completely
      remove the primary tumor and the associated lymph node metastasis at first-time
      thyroidectomy. After optimized surgery (total thyroidectomy plus central neck
      dissection), radioiodine ablation has very little influence on lymph node
      recurrence that now presents mostly as lateral neck node metastasis that was
      overlooked or incompletely resected at the time of initial surgery.

PMID- 30293501
TI  - Feasibility of Motivational Interviewing and Physical Activity Counseling
      Sessions for Improving Physical Activity Self-Management for Latina Women Either
      at Risk for or Diagnosed With Type 2 Diabetes Mellitus.
AB  - INTRODUCTION: Latinas have a greater chance of dying from diabetes than non
      Latina Whites. As a population group, the literature has shown that Latinas do
      not meet physical activity (PA) guidelines. Motivational interviewing (MI) is a
      patient-centered counseling method that promotes self-efficacy for behavior
      change. The purpose of the study was to examine the feasibility of using MI/PA
      counseling for self-management of type 2 diabetes mellitus with Latinas. METHODS:
      Latinas ( n = 12) were recruited from an occupational program in Southern
      California. Two MI and PA sessions were conducted over 2 months. Feasibility
      measures included recruitment, retention, protocol adherence, and attrition.
      Impact outcomes included PA, PA stage of change, and waist circumference.
      RESULTS: Participants attended all sessions and completed all questionnaires.
      Half progressed into a later stage of change for PA. DISCUSSION: Results suggest
      MI and PA counseling is feasible for improving PA with Latinas at risk/diagnosed
      with type 2 diabetes mellitus.

PMID- 30293502
TI  - Benefits of combining prevalent and incident cohorts: An application to myotonic
      dystrophy.
AB  - It is frequently of interest to estimate the time that individuals survive with a
      disease, that is, to estimate the time between disease onset and occurrence of a
      clinical endpoint such as death. Epidemiologic survival data are commonly
      collected from either an incident cohort, whose members' disease onset occurs
      after the study baseline date, or from a cohort with prevalent disease that is
      followed forward in time. Incident cohort survival data are limited by study
      termination, while prevalent cohort data provide biased (left-truncated) survival
      data. In this article, we investigate the advantages of a study design featuring
      simultaneous follow-up of prevalent and incident cohorts to the estimation of the
      survivor function. Our analyses are supported by simulations and illustrated
      using data on survival after myotonic dystrophy diagnosis from the United Kingdom
      Clinical Practice Research Datalink (CPRD). We demonstrate that the NPMLE using
      combined incident and prevalent cohort data estimates the true survivor function
      very well, even for moderate sample sizes, and ameliorates the disadvantages of
      using a purely incident or prevalent cohort.

PMID- 30293503
TI  - Dental age assessment on panoramic radiographs: Comparison between two
      generations of young Finnish subjects.
AB  - Objective To analyse the accuracy of a meta-analysis-based dental age assessment
      (DAA) method in Finnish paediatric patients and to compare the dental development
      between two generations of Finnish children. Methods Panoramic radiographs of
      Finnish Caucasian healthy children from two generations (early: born 1981-1984;
      subsequent: born 1996-2008) were analysed. All developing teeth on the left
      maxilla and mandible as well as the third permanent molars were analysed
      following Demirjian's classification. For each patient, dental age was calculated
      and compared with chronological age. Dental maturation patterns between the two
      groups were compared. Results The study included 200 Finnish Caucasian healthy
      children from two generations (early: aged 7-13 years; subsequent: aged 6-15
      years). In the early generation, DAA underestimated the chronological age by a
      mean of 3.15 years. The underestimation was only 0.11 years in patients < 10
      years, but 3.86 years in patients >= 10 years. In the subsequent generation, the
      dental age was overestimated by a mean of 0.34 years; by 0.40 years in patients <
      10 years and by 0.08 years in patients >= 10 years. Conclusions The present DAA
      method is applicable to current Finnish children. Differences in dental
      development between two generations of Finnish children were detected.

PMID- 30293504
TI  - Empiric antimicrobial treatment for asymptomatic sexual contacts of sexually
      transmitted infection in the era of antimicrobial resistance: time to rethink?
AB  - Prudent prescribing of antimicrobials is essential in ameliorating the public
      health problem of antimicrobial resistance. This retrospective audit assesses
      whether empiric antimicrobial treatment for asymptomatic sexual contacts of
      sexually transmitted infection is appropriate based on laboratory confirmation.

PMID- 30293505
TI  - Cuba's Strategy Toward Universal Health.
AB  - After 40 years of the Alma Ata Declaration on primary health care, the Pan
      American Journal of Public Health published an actualized overview of Cuban
      policies on health and well-being. It describes the longstanding and successful
      experience of this socialist country, developed in adverse and complex
      circumstances. The Cuban case remains one of the leading examples of a
      comprehensive governmental approach toward population health and well-being. The
      analysis underscores the essential role of continued political will toward
      population health.

PMID- 30293506
TI  - Osteoporosis in pituitary diseases: lessons for the clinic.
AB  - Osteoporosis is a systemic disease characterized by bone mass and density loss
      leading to fragility fractures. Osteoporosis due to endocrine disorders is an
      example of secondary osteoporosis. The harmful effects on bones are common in
      patients harboring pituitary tumors (acromegaly, prolactinoma, Cushing's disease)
      and suffering from hypopituitarism. Increased fracture risk and high healthcare
      costs of fractured patients are their consequences. The coexistence of some of
      these disorders and hypogonadism results in severe osteoporosis. The influence of
      the certain diseases, their activity and therapy and accompanying hypogonadism on
      bone turnover, bone mineral density and fracture incidence is presented.

PMID- 30293507
TI  - Review of growth hormone therapy in adolescents and young adults with Prader
      Willi syndrome.
AB  - Consensus guidelines from the Growth Hormone Research Society Workshop recommend
      growth hormone therapy in all children with genetically confirmed Prader-Willi
      syndrome (PWS) in combination with dietary, lifestyle and environmental
      interventions. As yet, however, there are limited published data regarding the
      use of growth hormone therapy in adolescents and young adults with PWS. This
      review focuses on the advantages and disadvantages of growth hormone therapy in
      this particular group. The risk of complications, challenges with consent for
      therapy, the need for contraception in females with PWS and the appropriate
      monitoring required are all factors which must be carefully considered in this
      challenging patient group. Transition from paediatric to adult services can be
      difficult for most adolescents, but especially so for PWS adolescents and should
      be undertaken under the care of experienced paediatric and adult endocrinologists
      and a multidisciplinary team approach. Further research is, however, still
      required in the management of PWS patients during adolescence.

PMID- 30293508
TI  - Potential novel therapeutic strategies from understanding adipocyte
      transdifferentiation mechanisms.
AB  - Brown adipocytes are located in discrete anatomical locations in both small
      mammals and in humans. 'Brown-like' adipocytes, also known as brite (brown in
      white) or beige adipocytes are found interspersed among white adipocytes in
      several fat depots. From a functional point of view, the activity of brown and
      brite cells is similar, that is, heat production mediated by uncoupling protein
      1. The morphology and expression of 'thermogenic' genes is also very similar in
      these two cell types. The origin of brite adipocytes is under intense
      investigation because enhancing their presence and activity has the potential to
      promote a healthy metabolic profile. Transdifferentiation mechanisms as well as
      de novo recruitment have been investigated. The characterization of the
      mechanisms involved in the recruitment and activation of brown/brite adipocytes
      in adult humans, could open the avenue for promising therapeutic strategies to
      curb metabolic diseases.

PMID- 30293509
TI  - Oral antidiabetic agents in gestational diabetes: a narrative review of current
      evidence.
AB  - Gestational diabetes mellitus (GDM) classically occurs when maternal glucose
      metabolism is unable to compensate the progressive development of insulin
      resistance that arises from the continuously rising diabetogenic placental
      hormones. Although most women can be treated satisfactorily with diet alone, some
      require more intensive treatment. Insulin has been the most reliable treatment
      strategy in GDM over several decades. Although a long time has passed since the
      publication of two randomized controlled trials suggesting comparable efficacy
      and safety of metformin and glibenclamide, international bodies have not yet
      approved these oral agents. However, with the consistently emerging efficacy and
      safety data of these two drugs in the past decade, they may perhaps open a rather
      new door. The aim of this narrative review is to critically evaluate the existing
      evidence regarding safety and efficacy of oral drugs in GDM accumulated since the
      first publication in year 2000, suggesting clinical equivalency of glibenclamide
      (glyburide).

PMID- 30293510
TI  - Endocrinology of bone/brain crosstalk.
AB  - Bone metabolism is regulated by the action of two skeletal cells: osteoblasts and
      osteoclasts. This process is controlled by many genetic, hormonal and lifestyle
      factors, but today more and more studies have allowed us to identify a neuronal
      regulation system termed 'bone-brain crosstalk', which highlights a direct
      relationship between bone tissue and the nervous system. The first documentation
      of an anatomic relationship between nerves and bone was made via a wood cut by
      Charles Estienne in Paris in 1545. His diagram demonstrated nerves entering and
      leaving the bones of a skeleton. Later, several studies were conducted on bone
      innervation and, as of today, many observations on the regulation of bone
      remodeling by neurons and neuropeptides that reside in the CNS have created a new
      research field, that is, neuroskeletal research.

PMID- 30293511
TI  - Colestilan for the treatment of hyperphosphatemia in chronic kidney disease
      patients on dialysis.
AB  - Chronic kidney disease in the later stages poses many treatment challenges.
      Hyperphosphatemia is one that is well-known and is often linked to increased
      cardiovascular morbidity/mortality. Currently, a number of phosphate binders are
      available that act to conserve serum phosphate at normal or near normal levels.
      However, it is the overall profile of all binders that needs to be taken into
      account and the risks and the potential benefits associated with each agent must
      be balanced when selecting a particular phosphate binder. It is known that
      calcium-based binders, although effective phosphate binders, may lead to
      hypercalcemia and/or positive calcium balance and cardiovascular calcification.
      One, new non-calcium phosphate binder, recently approved in Europe, is
      colestilan. Colestilan possesses a range of properties that may afford further
      advantages over simply reducing serum phosphate. This review assesses the
      pharmacology and clinical data of colestilan used to treat hyperphosphatemia in
      chronic kidney disease stage 5 patients on dialysis. The article was written
      based on literature searches using PubMed to find articles published on phosphate
      binders or colestilan over the last 10 years.

PMID- 30293512
TI  - An update on diabetes related skeletal fragility.
AB  - There are several mechanisms by which diabetes could affect bone mass and
      strength. These mechanisms include insulin deficiency; hyperglycemia; the
      accumulation of advanced glycation end products that may influence collagen
      characteristics; marrow adiposity and bone inflammation. Furthermore, associated
      diabetic complications and treatment with thaizolidinediones may also increase
      risk of fracturing. The following article provides its readers with an update on
      the latest information pertaining to diabetes related bone skeletal fragility. In
      the authors' opinion, future studies are needed in order to clarify the impact of
      different aspects of diabetes metabolism, glycemic control, and specific
      treatments for diabetes on bone. Given that dual energy x-ray absorptiometry is a
      poor predictor of bone morbidity in this group of patients, there is a need to
      explore novel approaches for assessing bone quality. It is important that we
      develop a better understanding of how diabetes affects bone in order to improve
      our ability to protect bone health and prevent fractures in the growing
      population of adults with diabetes.

PMID- 30293513
TI  - Cardiovascular risk profiles in Type 2 diabetes and the impact of geographical
      setting.
AB  - Cardiovascular (CV) disease is a leading morbidity and mortality in Type 2
      diabetes (T2DM). Previous studies have shown geographic differences in the
      prevalence of CV and renal diseases. A literature review of longitudinal (>=5
      years) studies including >=1000 T2DM patients and reporting CV endpoints was
      performed to compare risk profiles. Key differences between geographies included
      a relatively higher prevalence of microalbuminuria in East Asian relative to
      North American and European patients, which in turn is an important CV risk
      factor. Patients from East Asia also have a relatively higher incidence of stroke
      and lower incidence of coronary heart disease. Overall, there are differences in
      CV risk in T2DM patients between different regions and that long-term studies
      from Africa, the Middle East and Latin America are lacking.

PMID- 30293514
TI  - Improving diabetes diagnosis and management in myocardial infarction patients:
      overcoming clinical inertia.
AB  - Diabetes is underdiagnosed and undertreated among acute myocardial infarction
      (AMI) patients. The early diagnosis and treatment of diabetes during AMI
      facilitates improved risk stratification, use of appropriate revascularization
      strategies and secondary prevention medications, and timely initiation of
      glycemic therapy. Accurate diagnostic methods, such as hemoglobin A1c, should be
      evaluated for hospitalized AMI patients. In addition, efforts to improve the
      uptake of diabetes screening and management in the hospitalized setting should
      occur. Possible actions include the use of clinical information systems to
      generate physician reminders for diabetes detection and management, audit and
      feedback programs, and professional society initiatives to address diabetes
      screening and therapy initiation through clinical guidelines and performance
      measures. Through the application of both these and other efforts listed in the
      manuscript, the rates of undiagnosed and undertreated diabetes among AMI patients
      can be significantly reduced, which would lead to an improvement in both diabetic
      and cardiovascular outcomes.

PMID- 30293515
TI  - The neuropeptide Y-ergic system: potential therapeutic target against bone loss
      with obesity treatments.
AB  - Obesity is no longer considered to provide protection against osteoporosis.
      Moreover, treatments for obesity are now suspected of reducing bone mass. With
      the escalating incidence of obesity, combined with increases in the frequency,
      duration and intensity of interventions used to combat it, we face a potential
      increase in health burden due to osteoporotic fractures. The neuropeptide Y-ergic
      system offers a potential target for the prevention and anabolic treatment of
      bone loss in obesity, due to its dual role in the regulation of energy
      homeostasis and bone mass. Although the strongest stimulation of bone mass by
      this system appears to occur via indirect hypothalamic pathways involving Y2
      receptors (one of the five types of receptors for neuropeptide Y), Y1 receptors
      on osteoblasts (bone-forming cells) induce direct effects to enhance bone mass.
      This latter pathway may offer a suitable target for anti-osteoporotic treatment
      while also minimizing the risk of adverse side effects.

PMID- 30293516
TI  - Synthesizing Qualitative Data Sets to Improve the Design of Trials and Complex
      Health Interventions: A Worked Example.
AB  - Qualitative researchers are increasingly reanalyzing and synthesizing data sets
      from different studies, and this method has now been used across trials to inform
      trial methodology and delivery. Despite this work, however, limited guidance
      exists about how this method should be employed. This article details an example
      in which interview data collected during three primary care depression trials
      were brought together to explore trial participants' study and treatment
      journeys. It details the process involved and the decisions made. It also
      presents findings from this synthesis to illustrate how this method can be used
      to inform the development of future trials and complex interventions, through
      raising questions about how researchers currently define and design treatment
      arms and indicating what factors may improve or hinder participants' engagement
      with their allocated treatment.

PMID- 30293518
TI  - Autoimmune haemolytic anaemia associated with P. vivax malaria.
AB  - Autoimmune haemolytic anaemia due to malaria or following its treatment with
      artesunate is rare. A child presented with severe anaemia after being treated
      with artesunate for P. vivax malaria. Blood transfusion was difficult as cross
      matching showed major incompatibility; group O negative blood under the cover of
      steroids was transfused. Oral steroids were given for six weeks. The patient made
      a complete recovery.

PMID- 30293517
TI  - Verbal adynamia in parkinsonian syndromes: behavioral correlates and
      neuroanatomical substrate.
AB  - Verbal adynamia (impaired language generation, as during conversation) has not
      been assessed systematically in parkinsonian disorders. We addressed this in
      patients with Parkinson's dementia, progressive supranuclear palsy and
      corticobasal degeneration. All disease groups showed impaired verbal fluency and
      sentence generation versus healthy age-matched controls, after adjusting for
      general linguistic and executive factors. Dopaminergic stimulation in the
      Parkinson's group selectively improved verbal generation versus other cognitive
      functions. Voxel-based morphometry identified left inferior frontal and posterior
      superior temporal cortical correlates of verbal generation performance. Verbal
      adynamia warrants further evaluation as an index of language network dysfunction
      and dopaminergic state in parkinsonian disorders.

PMID- 30293519
TI  - The small RNA, SdsR, acts as a novel type of toxin in Escherichia coli.
AB  - Most small noncoding RNAs (sRNAs) are known to base pair with target mRNAs and
      regulate mRNA stability or translation to trigger various changes in the cell
      metabolism of Escherichia coli. The SdsR sRNA is expressed specifically during
      the stationary phase and represses tolC and mutS expression. However, it was not
      previously known whether the growth-phase-dependent regulation of SdsR is
      important for cell growth. Here, we ectopically expressed SdsR during the
      exponential phase and examined cell growth and survival. We found that ectopic
      expression of SdsR led to a significant and Hfq-dependent cell death with
      accompanying cell filamentation. This SdsR-driven cell death was alleviated by
      overexpression of RyeA, an sRNA transcribed on the opposite DNA strand,
      suggesting that SdsR/RyeA is a novel type of toxin-antitoxin (T/A) system in
      which both the toxin and the antitoxin are sRNAs. We defined the minimal region
      required for the SdsR-driven cell death. We also performed RNA-seq analysis and
      identified 209 genes whose expression levels were altered by more than two-fold
      following pulse expression of ectopic SdsR at exponential phase. Finally, we
      found that that the observed SdsR-driven cell death was mainly caused by the SdsR
      mediated repression of yhcB, which encodes an inner membrane protein.

PMID- 30293520
TI  - Lexical prediction in the aging brain: The effects of predictiveness and
      congruency on the N400 ERP component.
AB  - Although the N400 ERP component has been extensively studied in younger adults,
      the underlying mechanisms are still unclear. In older adults, N400 ERP studies
      have shown less efficient use of context compared to younger adults. Here, we
      asked whether the mechanisms underlying the N400 effect are the same in terms of
      predictiveness and congruency in younger and older adults. We used a simple
      picture-word matching task in which we crossed predictiveness and congruency. Our
      results indicate a three-way interaction between predictiveness, congruency, and
      age, in that, younger adults showed an N400 effect only in strongly constrained
      conditions; whereas, older adults showed an effect in both strongly- and weakly
      constrained conditions. This interaction was not modulated by language experience
      or cognitive decline. Our results support either two separate mechanisms (lexical
      access and integration) that run in parallel and are modulated by age or a common
      prediction error mechanism that changes with age.

PMID- 30293521
TI  - A Rigorous Approach to Large-Scale Elicitation and Analysis of Patient
      Narratives.
AB  - Patient narratives have emerged as promising vehicles for making health care more
      responsive by helping clinicians to better understand their patients'
      expectations, perceptions, or concerns and encouraging consumers to engage with
      information about quality. A growing number of websites incorporate patients'
      comments. But existing comments have fragmentary content, fail to represent less
      vocal patients, and can be manipulated to "manage" providers' reputations. In
      this article, we offer the first empirical test of the proposition that patient
      narratives can be elicited rigorously and reliably using a five-question protocol
      that can be incorporated into large-scale patient experience surveys. We tested
      whether elicited narratives about outpatient care are complete (report all facets
      of patient experience), balanced (convey an accurate mix of positive and negative
      events), meaningful (have a coherent storyline), and representative (draw fulsome
      narratives from all relevant subsets of patients). The tested protocol is strong
      on balance and representativeness, more mixed on completeness and meaningfulness.

PMID- 30293522
TI  - Patterns of recognition of Arabic consonants by non-native children with cochlear
      implants and normal hearing.
AB  - OBJECTIVE: This study examined the patterns of recognition of Arabic consonants,
      via information transmission analysis for phonological features, in a group of
      Malay children with normal hearing (NH) and cochlear implants (CI). METHOD: A
      total of 336 and 616 acoustic tokens were collected from six CI and 11 NH Malay
      children, respectively. The groups were matched for hearing age and duration of
      exposure to Arabic sounds. All the 28 Arabic consonants in the form of consonant
      vowel /a/ were presented randomly twice via a loudspeaker at approximately 65 dB
      SPL. The participants were asked to repeat verbally the stimulus heard in each
      presentation. RESULTS: Within the native Malay perceptual space, the two groups
      responded differently to the Arabic consonants. The dispersed uncategorized
      assimilation in the CI group was distinct in the confusion matrix (CM), as
      compared to the NH children. Consonants /h/, /t?/, /s?/ and /?/ were difficult
      for the CI children, while the most accurate item was /k/ (84%). The CI group
      transmitted significantly reduced information, especially for place feature
      transmission, then the NH group (p < 0.001). Significant interactions between
      place-hearing status and manner-hearing status were also obtained, suggesting
      there were information transmission differences in the pattern of consonants
      recognition between the study groups. CONCLUSION: CI and NH Malay children may be
      using different acoustic cues to recognize Arabic sounds, which contribute to the
      different assimilation categories' patterns within the Malay perceptual space.

PMID- 30293524
TI  - Pacing profile in the main international open-water swimming competitions.
AB  - PURPOSE: Different aspects of pacing in endurance events have been investigated,
      however, there are very limited information on pacing strategies during open
      water swimming. The aim was to describe and compare the pacing profile used by
      male and female open-water swimmers (OW-swimmers) during the 5-, 10- and 25 km
      races in the main international competitions. METHODS: A total of 438
      performances were analysed for 5 km, 579 for 10 km and 189 for 25 km, from 2012
      to 2017. Swimmers were divided into four groups based on finishing time. G1 whose
      finishing times were within 0.5% of the winner's time, G2 between 0.51% and 1%
      slower than winner's time; G3 between 1.1% and 2% slower than winner's time; G4
      over 2% of winner's time. Kolmogorov-Smirnov test was used to verify the normal
      distribution of data and repeated measures ANOVA was performed. RESULTS: G1
      adopted a negative pacing and significantly increased the speed in the last split
      compared with the other groups during the 5-, 10- and 25-km races in both males
      and females (p < .001). During the 5- and 10-km race, the last split speed of G1
      was significantly faster compared to the other groups in both males and females
      (p < .05). CONCLUSIONS: OW-swimmers that used a conservative approach remaining
      in G1 until the finish of the race, increase the possibility to win a medal in
      the main international competitions.

PMID- 30293523
TI  - Are professional young rugby league players eating enough? Energy intake,
      expenditure and balance during a pre-season.
AB  - Due to the unique energetic demands of professional young collision sport
      athletes, accurate assessment of energy balance is required. Consequently, this
      is the first study to simultaneously investigate the energy intake, expenditure
      and balance of professional young rugby league players across a pre-season
      period. The total energy expenditure of six professional young male rugby league
      players was measured via doubly labelled water over a fourteen-day assessment
      period. Resting metabolic rate was measured and physical activity level
      calculated. Dietary intake was reported via Snap-N-Send over a non-consecutive
      ten-day assessment period, alongside changes in fasted body mass and hydration
      status. Accordingly, energy balance was inferred. The mean (standard deviation)
      difference between total energy intake (16.73 (1.32) MJ.day-1) and total energy
      expenditure (18.36 (3.05) MJ.day-1) measured over the non-consecutive ten-day
      period was unclear (-1.63 (1.73) MJ.day-1; ES = 0.91 +/- 1.28; p = 0.221). This
      corresponded in a most likely trivial decrease in body mass (-0.65 (0.78) kg; ES
      = 0.04 +/- 0.03; p = 0.097). Resting metabolic rate and physical activity level
      across the fourteen-day pre-season period was 11.20 (2.16) MJ.day-1 and 1.7
      (0.2), respectively. For the first time, this study utilises gold standard
      assessment techniques to elucidate the distinctly large energy expenditures of
      professional young rugby league players across a pre-season period, emphasising a
      requirement for equally large energy intakes to achieve targeted body mass and
      composition adaptations. Accordingly, it is imperative that practitioners
      regularly assess the energy balance of professional young collision-sport
      athletes to ensure their unique energetic requirements are achieved.

PMID- 30293525
TI  - Author's reply.

PMID- 30293526
TI  - Language bias and comprehensive meta-analysis of folate for unipolar depression.

PMID- 30293527
TI  - Age-specific response of skeletal muscle extracellular matrix to acute resistance
      exercise: A pilot study.
AB  - The extracellular matrix (ECM) plays an essential role in the development, growth
      and repair of skeletal muscles and serves to transmit contractile force. However,
      its regulation is poorly understood. This study investigates the age-specificity
      of the effects of acute resistance exercise on ECM gene expression. To this
      purpose, five young (YM, 23.8 +/- 2.2 yrs.) and 5 elderly (EM, 66.8 +/- 4.1 yrs.)
      men performed one session of unilateral leg press and leg extension exercises.
      Six hours post-exercise, biopsies were taken from the vastus lateralis muscles of
      both legs. A PCR array was used to profile the expression of 84 ECM-related
      genes, of which 6 were validated by qPCR. The PCR array found 9 and 4 ECM
      associated genes to be selectively altered (>1.5-fold change) in YM or EM only.
      Four further genes were upregulated in YM but downregulated in EM. Of the 6 genes
      validated on individual samples MMP9 expression increased in YM (9.7-fold) and
      decreased (0.2-fold) in EM. MMP15 was downregulated in EM only (0.6-fold). A
      significant correlation between leg extension 1 RM and changes in COL7A1
      expression (rho = 0.71) suggests a potential influence of fitness levels. In
      conclusion, acute resistance exercise affects ECM gene expression at least partly
      in an age-specific manner. The altered expression of genes encoding matrix
      metalloproteinases (MMP3, MMP9, MMP15) highlights the role of remodelling
      processes in the response to an acute bout of resistance exercise. Larger studies
      are required to verify the age-associated differences in gene expression profiles
      and establish their functional implications.

PMID- 30293528
TI  - Addressing disrespect and abuse during childbirth in facilities.

PMID- 30293530
TI  - Onchocerca volvulus as a risk factor for developing epilepsy in onchocerciasis
      endemic regions in the Democratic Republic of Congo: a case control study.
AB  - BACKGROUND: A high prevalence of epilepsy has been observed in onchocerciasis
      endemic areas in the Democratic Republic of Congo (DRC). With this study we aimed
      to investigate whether Onchocerca volvulus infection is a risk factor for
      developing epilepsy in onchocerciasis endemic regions in the DRC. METHODS:
      Between October and December 2015, a multi-centre case control study was
      performed in onchocerciasis endemic health zones (HZ) in the DRC: one study site
      was situated in Tshopo Province in the HZ of Wanierukula (village of Salambongo)
      where there had been 13 annual community distributions of treatment with
      ivermectin (CDTI), a second was situated in Ituri Province in the HZ of Logo
      (village of Draju) where ivermectin had never been distributed and in the HZ of
      Rethy (village of Rassia) where there had been THREE CDTI annual campaigns before
      the study. Individuals with unprovoked convulsive epilepsy of unknown etiology
      were enrolled as cases (n = 175). Randomly selected healthy members of families
      without epilepsy cases from the same village and age-groups and were recruited as
      controls (n = 170). RESULTS: Onchocerciasis associated symptoms (e.g., itching
      and abnormal skin) were more often present in cases compared to controls
      (respectively, OR = 2.63, 95% CI: 1.63-4.23, P <  0.0001 and OR = 3.23, 95% CI:
      1.48-7.09, P = 0.0034). A higher number of cases was found to present with
      microfilariae in skin snips and with O. volvulus IgG4 antibodies in the blood
      compared to controls. Moreover, the microfilariae load in skin snips was 3-10
      times higher in cases than controls. CONCLUSIONS: This case control study
      confirms that O. volvulus is a risk factor for developing epilepsy in
      onchocerciasis endemic regions in the DRC.

PMID- 30293532
TI  - The first case of thrombocytopenia, anasarca, fever, renal impairment or
      reticulin fibrosis, and organomegaly (TAFRO) syndrome with unilateral adrenal
      necrosis: a case report.
AB  - BACKGROUND: TAFRO syndrome, which was first reported in 2010 in Japan, is a
      relatively rare disease characterized by thrombocytopenia, anasarca, fever, renal
      impairment, reticulin fibrosis, and organomegaly. Although this disease is
      considered similar to multicentric Castleman disease, some of the clinical
      features, such as thrombocytopenia, are different from typical cases of
      multicentric Castleman disease. In addition, the etiology of TAFRO syndrome
      remains unknown and controversial. There have only been a few cases of TAFRO
      syndrome complicated with adrenal gland lesions, and all of them have had
      hemorrhagic involvement. CASE PRESENTATION: This report describes the case of a
      46-year-old Asian man who presented with fever, epigastric pain, and back pain
      for 1 month. A computed tomographic scan revealed ascites, mild lymphadenopathy,
      and left adrenal necrosis without hemorrhage. A blood test showed
      thrombocytopenia, anemia, and elevated C-reactive protein, alkaline phosphatase,
      and creatinine levels. Based on the edema, severe thrombocytopenia, fever,
      reticulin myelofibrosis shown by bone marrow biopsy, mild lymphadenopathy, and
      progressive renal insufficiency, we diagnosed this patient as having TAFRO
      syndrome. He was successfully treated by immediate administration of
      glucocorticoids and tocilizumab. CONCLUSIONS: There have been no previous reports
      of a case of TAFRO syndrome complicated with adrenal necrosis. Because the biopsy
      of the left adrenal gland revealed necrosis without any evidence of hemorrhage,
      we concluded that the unilateral adrenal necrosis in this case was caused by
      either ischemia from infarction or organomegaly itself under severe
      hypercytokinemia. This unusual clinical course is useful for further analysis of
      the etiology of TAFRO syndrome.

PMID- 30293531
TI  - Vaccination with chemically attenuated Plasmodium falciparum asexual blood-stage
      parasites induces parasite-specific cellular immune responses in malaria-naive
      volunteers: a pilot study.
AB  - BACKGROUND: The continuing morbidity and mortality associated with infection with
      malaria parasites highlights the urgent need for a vaccine. The efficacy of sub
      unit vaccines tested in clinical trials in malaria-endemic areas has thus far
      been disappointing, sparking renewed interest in the whole parasite vaccine
      approach. We previously showed that a chemically attenuated whole parasite
      asexual blood-stage vaccine induced CD4+ T cell-dependent protection against
      challenge with homologous and heterologous parasites in rodent models of malaria.
      METHODS: In this current study, we evaluated the immunogenicity and safety of
      chemically attenuated asexual blood-stage Plasmodium falciparum (Pf) parasites in
      eight malaria-naive human volunteers. Study participants received a single dose
      of 3 * 107 Pf pRBC that had been treated in vitro with the
      cyclopropylpyrolloindole analogue, tafuramycin-A. RESULTS: We demonstrate that Pf
      asexual blood-stage parasites that are completely attenuated are immunogenic,
      safe and well tolerated in malaria-naive volunteers. Following vaccination with a
      single dose, species and strain transcending Plasmodium-specific T cell responses
      were induced in recipients. This included induction of Plasmodium-specific
      lymphoproliferative responses, T cells secreting the parasiticidal cytokines, IFN
      gamma and TNF, and CD3+CD45RO+ memory T cells. Pf-specific IgG was not detected.
      CONCLUSIONS: This is the first clinical study evaluating a whole parasite blood
      stage malaria vaccine. Following administration of a single dose of completely
      attenuated Pf asexual blood-stage parasites, Plasmodium-specific T cell responses
      were induced while Pf-specific antibodies were not detected. These results
      support further evaluation of this chemically attenuated vaccine in humans. TRIAL
      REGISTRATION: Trial registration: ACTRN12614000228684 . Registered 4 March 2014.

PMID- 30293533
TI  - Transmission of resistant Gram-negative bacteria to healthcare personnel gowns
      and gloves during care of residents in community-based nursing facilities.
AB  - OBJECTIVE: To estimate the risk of transmission of antibiotic-resistant Gram
      negative bacteria (RGNB) to gowns and gloves worn by healthcare personnel (HCP)
      when providing care to residents of community-based nursing facilities to
      identify the types of care and resident characteristics associated with
      transmission. DESIGN: Prospective observational study.Settings and
      participantsResidents and HCP from 13 community-based nursing facilities in
      Maryland and Michigan. METHODS: Perianal swabs were collected from residents and
      cultured to detect RGNB. HCP wore gowns and gloves during usual care activities,
      and at the end of each interaction, these were swabbed in a standardized manner.
      Transmission of RGNB from a colonized resident to gowns and gloves was estimated.
      Odds ratios (ORs) of transmission associated with type of care or resident
      characteristic were calculated. RESULTS: We enrolled 403 residents and their HCP
      in this study. Overall, 19% of enrolled residents with a perianal swab (n=399)
      were colonized with at least 1 RGNB. RGNB transmission to either gloves or gowns
      occurred during 11% of the 584 interactions. Showering the resident, hygiene or
      toilet assistance, and wound dressing changes were associated with a high risk of
      transmission. Glucose monitoring and assistance with feeding or medication were
      associated with a low risk of transmission. Residents with a pressure ulcer were
      3 times more likely to transmit RGNB than residents without one (OR, 3.3; 95%
      confidence interval [CI], 1.0-11.1). CONCLUSIONS: Gown and glove use in community
      nursing facilities should be prioritized for certain residents and care
      interactions that are deemed a high risk for transmission.

PMID- 30293534
TI  - Temporal dynamics of Middle East respiratory syndrome coronavirus in the Arabian
      Peninsula, 2012-2017.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) remains a notable disease
      and poses a significant threat to global public health. The Arabian Peninsula is
      considered a major global epicentre for the disease and the virus has crossed
      regional and continental boundaries since 2012. In this study, we focused on
      exploring the temporal dynamics of MERS-CoV in human populations in the Arabian
      Peninsula between 2012 and 2017, using publicly available data on case counts and
      combining two analytical methods. Disease progression was assessed by quantifying
      the time-dependent reproductive number (TD-Rs), while case series temporal
      pattern was modelled using the AutoRegressive Integrated Moving Average (ARIMA).
      We accounted for geographical variability between three major affected regions in
      Saudi Arabia including Eastern Province, Riyadh and Makkah. In Saudi Arabia, the
      epidemic size was large with TD-Rs >1, indicating significant spread until 2017.
      In both Makkah and Riyadh regions, the epidemic progression reached its peak in
      April 2014 (TD-Rs > 7), during the highest incidence period of MERS-CoV cases. In
      Eastern Province, one unique super-spreading event (TD-R > 10) was identified in
      May 2013, which comprised of the most notable cases of human-to-human
      transmission. Best-fitting ARIMA model inferred statistically significant
      biannual seasonality in Riyadh region, a region characterised by heavy seasonal
      camel-related activities. However, no statistical evidence of seasonality was
      identified in Eastern Province and Makkah. Instead, both areas were marked by an
      endemic pattern of cases with sporadic outbreaks. Our study suggested new
      insights into the epidemiology of the virus, including inferences about epidemic
      progression and evidence for seasonality. Despite the inherent limitations of the
      available data, our conclusions provide further guidance to currently implement
      risk-based surveillance in high-risk populations and, subsequently, improve
      related interventions strategies against the epidemic at country and regional
      levels.

PMID- 30293535
TI  - Preventing hospital-acquired Legionnaires' disease: A snapshot of clinical
      practices and water management approaches in US acute-care hospitals.
AB  - In 2017, we surveyed 101 SHEA Research Network hospitals regarding Legionnaires'
      disease (LD). Of 29 respondents, 94% have or are developing a water management
      plan with varying characteristics and personnel engaged. Most LD diagnostic
      testing is limited to urine antigen testing. Many opportunities to improve LD
      prevention and diagnosis exist.

PMID- 30293536
TI  - The changing epidemiology worldwide of Mycobacterium ulcerans.
AB  - Mycobacterium ulcerans is recognised as the third most common mycobacterial
      infection worldwide. It causes necrotising infections of skin and soft tissue and
      is classified as a neglected tropical disease by the World Health Organization
      (WHO). However, despite extensive research, the environmental reservoir of the
      organism and mode of transmission of the infection to humans remain unknown. This
      limits the ability to design and implement public health interventions to
      effectively and consistently prevent the spread and reduce the incidence of this
      disease. In recent years, the epidemiology of the disease has changed. In most
      endemic regions of the world, the number of cases reported to the WHO are
      reducing, with a 64% reduction in cases reported worldwide in the last 9 years.
      Conversely, in a smaller number of countries including Australia and Nigeria,
      reported cases are increasing at a rapid rate, new endemic areas continue to
      appear, and in Australia cases are becoming more severe. The reasons for this
      changing epidemiology are unknown. We review the epidemiology of M. ulcerans
      disease worldwide, and document recent changes. We also outline and discuss the
      current state of knowledge on the ecology of M. ulcerans, possible transmission
      mechanisms to humans and what may be enabling the spread of M. ulcerans into new
      endemic areas.

PMID- 30293537
TI  - A Further Comment on 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue
      Specific Neural Expression and Potential Nootropic Drug Targets' by Lam et al.
AB  - Lam et al. (2018) respond to a commentary of their paper entitled 'Large-Scale
      Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and
      Potential Nootropic Drug Targets' Lam et al. (2017). While Lam et al. (2018) have
      now provided the recommended quality control metrics for their paper, problems
      remain. Specifically, Lam et al. (2018) do not dispute that the results of their
      multi-trait analysis of genome-wide association study (MTAG) analysis has
      produced a phenotype with a genetic correlation of one with three measures of
      education, but do claim the associations found are specific to the trait of
      cognitive ability. In this brief paper, it is empirically demonstrated that the
      phenotype derived by Lam et al. (2017) is more genetically similar to education
      than cognitive ability. In addition, it is shown that of the genome-wide
      significant loci identified by Lam et al. (2017) are loci that are associated
      with education rather than with cognitive ability.

PMID- 30293538
TI  - Maternal antenatal daytime sleepiness and child neuropsychiatric and
      neurocognitive development.
AB  - BACKGROUND: The prevalence of sleep problems among pregnant women is over 50%,
      and daytime sleepiness is among the most common sleep problems. Previous studies
      have associated antenatal sleep problems with adverse maternal health and
      neonatal outcomes, but the consequences of antenatal sleep problems and
      particularly daytime sleepiness on child psychological development have not been
      assessed prospectively. METHODS: In this prospective cohort study including 111
      mother-child dyads, we examined the associations of maternal daytime sleepiness
      during pregnancy, assessed at 17 and 28 weeks of gestation using the Epworth
      Sleepiness Scale, with child neuropsychiatric problems and neuropsychological
      development, assessed with mother-rated questionnaires and individually
      administered neuropsychological tests, at child age 2.6-5.7 years (mean = 4.3
      years). RESULTS: Independently of sociodemographic and perinatal covariates and
      maternal depressive and anxiety symptoms during and/or after pregnancy, maternal
      antenatal daytime sleepiness was associated with increased total [unstandardized
      regression coefficient (B) = 0.25 standard deviation (s.d.) units; 95% confidence
      interval (CI) 0.01-0.48] and internalizing (B = 0.25 s.d.s: 95% CI 0.01-0.49)
      psychiatric problems and ADHD symptoms (B = 0.27 s.d.s: 95% CI 0.04-0.50) in
      children, and with poorer executive function, particularly in the areas of
      attention, working memory and inhibitory control (B = -0.39 s.d.s: 95% CI -0.69
      to -0.10). CONCLUSIONS: Maternal antenatal daytime sleepiness carries adverse
      consequences for offspring psychological development. The assessment of sleep
      problems may be an important addition to standard antenatal care.

PMID- 30293539
TI  - The limitations of equivalence and non-inferiority trials.
AB  - Equivalence and non-inferiority trials are becoming more and more popular.
      Typically, they compare the effects of a treatment of interest with the current
      gold-standard treatment as the comparator. However, for this approach, the
      definition of equivalence or non-inferiority margins (NIM) is crucial, and no
      clear rules for their definition exist. We criticized the practice of these
      trials of being over-inflationary in favor of (erroneous) equivalence, and we
      outlined our critique with some study examples comparing psychodynamic treatments
      with current first-line treatments for mental disorders. Here we answer to a
      commentary of Leichsenring et al. to our paper. Although focusing on our
      commentary, these authors are less arguing against our conclusions, but they
      address issues of study conduct, and lack of appreciation of our examples.
      However, the crucial question is: What is the risk of erroneous equivalence
      conclusions that we want to accept as responsible clinicians and scientists? We
      conclude that the scientific community has to define better and clearer criteria
      for NIMs. We do not believe that it is ethically justifiable to recommend a
      treatment that is 10 or 20% less effective than the current gold standard
      interventions.

PMID- 30293540
TI  - New product, old problem(s): multistate outbreak of Salmonella Paratyphi B
      variant L(+) tartrate(+) infections linked to raw sprouted nut butters, October
      2015.
AB  - A cluster of Salmonella Paratyphi B variant L(+) tartrate(+) infections with
      indistinguishable pulsed-field gel electrophoresis patterns was detected in
      October 2015. Interviews initially identified nut butters, kale, kombucha, chia
      seeds and nutrition bars as common exposures. Epidemiologic, environmental and
      traceback investigations were conducted. Thirteen ill people infected with the
      outbreak strain were identified in 10 states with illness onset during 18 July-22
      November 2015. Eight of 10 (80%) ill people reported eating Brand A raw sprouted
      nut butters. Brand A conducted a voluntary recall. Raw sprouted nut butters are a
      novel outbreak vehicle, though contaminated raw nuts, nut butters and sprouted
      seeds have all caused outbreaks previously. Firms producing raw sprouted
      products, including nut butters, should consider a kill step to reduce the risk
      of contamination. People at greater risk for foodborne illness may wish to
      consider avoiding raw products containing raw sprouted ingredients.

PMID- 30293541
TI  - Age, Gender and Mechanism of Injury Interactions in Post-Concussion Syndrome.
AB  - BACKGROUND: Certain factors such as age and gender seem to affect the risk of
      developing post-concussion syndrome (PCS). We assessed the interactions between
      age, gender, concussion history and mechanism of injury in PCS patients so that a
      better understanding could guide the development of targeted prevention
      strategies. METHODS: Demographic data including age, gender, concussion mechanism
      of injury and concussion history were collected from (1) a prospective study
      evaluating PCS biomarkers and (2) a retrospective chart review of PCS patients. A
      total of 437 PCS patients who were assessed at the Canadian Concussion Centre or
      Toronto Western Hospital, Toronto, ON, were included. RESULTS: Overall, there
      were more men with PCS; however, a greater percentage of women had PCS after a
      single concussion. The results showed that age, gender and concussion history are
      conditionally dependent on the mechanism of injury, and independent of one
      another. The relative frequency of having PCS was greater in the following
      instances: (1) being a woman and having had concussion from a fall or motor
      vehicle collision (MVC), (2) being older and having had concussion from a fall or
      MVC or (3) having a single concussion with cause being MVC or fall. CONCLUSION:
      In patients with PCS, age and gender interact with the mechanism of injury to
      influence the risk of concussion. Targeted prevention strategies may be essential
      to prevent injuries leading to PCS.

PMID- 30293542
TI  - Dietary starch and rhubarb supplement increase ruminal dissolved hydrogen without
      altering rumen fermentation and methane emissions in goats.
AB  - Hydrogen is an important intermediate that is produced during carbohydrate
      fermentation to volatile fatty acid and utilized by methanogens to produce
      methane in the rumen. Ruminal volatile fatty acid and dissolved methane
      concentrations are more than 500 times greater than dissolved hydrogen
      concentration. Therefore, we hypothesized that dissolved hydrogen might have a
      higher sensitivity in response to dietary changes compared with volatile fatty
      acid and dissolved methane. Using goats, we investigated the effects of
      increasing dietary starch content (maize replaced with wheat bran) and
      supplementing with rhubarb rhizomes and roots on the relationships among
      dissolved hydrogen, dissolved methane and other fermentation end products. The
      study was conducted in a replicated 4*4 Latin square with a 2*2 factorial
      arrangement of four treatments: two starch levels (220 v. 320 g/kg dry matter
      (DM)), without and with rhubarb supplement (0% v. 2.8% of total mixed ration).
      Increased dietary starch and rhubarb supplementation did not alter volatile fatty
      acid concentrations or methane emissions in terms of g/day, g/g DM intake and g/g
      organic matter digested. However, goats fed the high-starch diet had greater
      dissolved hydrogen (P=0.005) and relative abundance of Selenomonas ruminantium
      (P<0.01), and lower (P=0.02) copy number of protozoa than those fed the low
      starch diet. Rhubarb increased ruminal dissolved H2 (P=0.03) and total volatile
      fatty acid concentration (P<0.001), but decreased copies of bacteria (P=0.002).
      In conclusion, dissolved hydrogen appears to be more sensitive to dietary changes
      with starch content and rhubarb supplementation, when compared with volatile
      fatty acid concentrations and methane production.

PMID- 30293543
TI  - Multilocus sequencing-based evolutionary analysis of 52 strains of Burkholderia
      pseudomallei in Hainan, China.
AB  - Previously, we reported a phylogenetic study of 98 Burkholderia pseudomallei
      clinical isolates from Hainan, China. Here, we update the B. pseudomallei strain
      library with 52 strains from newly identified cases dating from 2014 to 2017,
      analysed by multilocus sequence typing. Twenty-two sequence types (STs) were
      identified from the 52 cases, illustrating high genetic diversity; five of them
      (ST1480, ST1481, ST1482, ST1483 and ST1484) were novel. ST46, ST50 and ST58
      predominated (34.6%) as was the case in the previous study (35.7%). An e-BURST
      map of the ST profiles of the two collections of isolates showed their genetic
      foundation to be largely unchanged. Neighbour-joining tree analysis was
      suggestive of a close phylogenetic relationship between the novel STs from this
      series and those first reported from Hainan (ST1105, ST1099, ST55 and ST1095).
      Moreover, the two novel STs (1481 and 1483) showed close similarity to ST58 which
      originated in Thailand indicating a close relationship between B. pseudomallei
      strains from both countries. The previously described allele profiles gmhD-36 and
      lepA-68 were found for the first time in our strain collections. Our study
      emphasises the importance of monitoring the epidemiological status and
      evolutionary trends of B. pseudomallei in China.

PMID- 30293544
TI  - Effects of Virtual Reality Simulation on Worker Emergency Evacuation of Neonates.
AB  - OBJECTIVE: This study examined differences in learning outcomes among newborn
      intensive care unit (NICU) workers who underwent virtual reality simulation (VRS)
      emergency evacuation training versus those who received web-based clinical
      updates (CU). Learning outcomes included a) knowledge gained, b) confidence with
      evacuation, and c) performance in a live evacuation exercise. METHODS: A
      longitudinal, mixed-method, quasi-experimental design was implemented utilizing a
      sample of NICU workers randomly assigned to VRS training or CUs. Four VRS
      scenarios were created that augmented neonate evacuation training materials.
      Learning was measured using cognitive assessments, self-efficacy questionnaire
      (baseline, 0, 4, 8, 12 months), and performance in a live drill (baseline, 12
      months). Data were collected following training and analyzed using mixed model
      analysis. Focus groups captured VRS participant experiences. RESULTS: The VRS and
      CU groups did not statistically differ based upon the scores on the Cognitive
      Assessment or perceived self-efficacy. The virtual reality group performance in
      the live exercise was statistically (P<.0001) and clinically (effect size of
      1.71) better than that of the CU group. CONCLUSIONS: Training using VRS is
      effective in promoting positive performance outcomes and should be included as a
      method for disaster training. VRS can allow an organization to train, test, and
      identify gaps in current emergency operation plans. In the unique case of
      disasters, which are low-volume and high-risk events, the participant can have
      access to an environment without endangering themselves or clients. (Disaster Med
      Public Health Preparedness. 2018; page 1 of 8).

PMID- 30293545
TI  - Human Umbilical Cord Blood Plasma Alleviates Age-related Olfactory Dysfunction by
      Attenuating Peripheral TNF-alpha expression.
AB  - Social requirements are needed for living in an aging society and individual
      longevity. Among them, improved health and medical cares, appropriate for an
      aging society are strongly demanded. Human cord blood-derived plasma (hUCP) has
      recently emerged for its unique anti-aging effects. In this study, we
      investigated brain rejuvenation, particularly olfactory function, that could be
      achieved by a systemic administration of young blood and its underlying
      mechanisms. Older than 24-month-old mice were used as an aged group and
      administered with intravenous injection of hUCP repetitively, eight times. Anti
      aging effect of hUCP on olfactory function was evaluated by buried food finding
      test. To investigate the mode of action of hUCP, brain, serum and spleen of mice
      were collected for further ex vivo analyses. Systemic injection of hUCP improved
      aging-associated olfactory deficits, reducing time for finding food. In the
      brain, although an infiltration of activated microglia and its expression of
      cathepsin S remarkably decreased, significant changes of proinflammatory factors
      were not detected. Conversely, peripheral immune balance distinctly switched from
      predominance of Type 1 helper T (Th1) cells to alternative regulatory T cells
      (Tregs). These findings indicate that systemic administration of hUCP attenuates
      age-related neuroinflammation and subsequent olfactory dysfunction by modulating
      peripheral immune balance toward Treg cells, suggesting another therapeutic
      function and mechanism of hUCP administration.

PMID- 30293546
TI  - Interferon-gamma-mediated Secretion of Tryptophanyl-tRNA Synthetases Has a Role
      in Protection of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells
      Against Experimental Colitis.
AB  - Mesenchymal stem cells (MSCs) are multipotent adult stem cells that present
      immunosuppressive effects in experimental and clinical trials targeting various
      rare diseases including inflammatory bowel disease (IBD). In addition, recent
      studies have reported tryptophanyl-tRNA synthetase (WRS) possess uncanonical
      roles such as angiostatic and anti-inflammatory effects. However, little is known
      about the function of WRS in MSC-based therapy. In this study, we investigated if
      a novel factor, WRS, secreted from MSCs has a role in amelioration of IBD
      symptoms and determined a specific mechanism underlying MSC therapy. Experimental
      colitis was induced by administration of 3% DSS solution to 8-week-old mice and
      human umbilical cord blood-derived MSCs (hUCB-MSCs) were injected
      intraperitoneally. Secretion of WRS from hUCB-MSCs and direct effect of WRS on
      isolated CD4+ T cells was determined via in vitro experiments and hUCB-MSCs
      showed significant therapeutic rescue against experimental colitis. Importantly,
      WRS level in serum of colitis induced mice decreased and recovered by
      administration of MSCs. Through in vitro examination, WRS expression of hUCB-MSCs
      increased when cells were treated with interferon-gamma (IFN-gamma). WRS was
      evaluated and revealed to have a role in inhibiting activated T cells by inducing
      apoptosis. In summary, IFN-gamma-mediated secretion of WRS from MSCs has a role
      in suppressive effect on excessive inflammation and disease progression of IBD
      and brings new highlights in the immunomodulatory potency of hUCB-MSCs.

PMID- 30293547
TI  - Overexpression of CXCL2 inhibits cell proliferation and promotes apoptosis in
      hepatocellular carcinoma.
AB  - C-X-C motif chemokine ligand 2 (CXCL2) is a small secreted protein that exhibits
      a structure similar to the proangiogenic subgroup of the CXC chemokine family.
      Recently, accumulating evidence suggests that chemokines play a pivotal role in
      cancer progression and carcinogenesis. We examined the expression levels of 7
      types of ELR+ CXCLs messenger RNA (mRNA) in 264 clinical samples. We found that
      CXCL2 expression was stably down-regulated in 94% of hepatocellular carcinoma
      (HCC) specimens compared with paired adjacent normal liver tissues and some HCC
      cell lines. Moreover, CXCL2 overexpression profoundly attenuated HCC cell
      proliferation and growth and induced apoptosis in vitro. In animal studies, we
      found that overexpressing CXCL2 by lentivirus also apparently inhibited the size
      and weight of subcutaneous tumours in nude mice. Furthermore, we demonstrated
      that CXCL2 induced HCC cell apoptosis via both nuclear and mitochondrial
      apoptosis pathways. Our results indicate that CXCL2 negatively regulates the cell
      cycle in HCC cells via the ERK1/2 signalling pathway. These results provide new
      insights into HCC and may ultimately lead to the discovery of innovative
      therapeutic approaches of HCC.

PMID- 30293548
TI  - Leptin stimulates IGF-1 transcription by activating AP-1 in human breast cancer
      cells.
AB  - Leptin, an adipokine regulating energy metabolism, appears to be associated with
      breast cancer progression. Insulin-like growth factor-1 (IGF-1) mediates the
      pathogenesis of breast cancer. The regulation of IGF-1 expression by leptin in
      breast cancer cells is unclear. Here, we found that leptin upregulates IGF-1
      expression at the transcriptional level in breast cancer cells. Activating
      protein-1 (AP-1)-binding element within the proximal region of IGF-1 was
      necessary for leptin-induced IGF-1 promoter activation. Forced expression of AP-1
      components, c-FOS or c-JUN, enhanced leptin-induced IGF-1 expression, while
      knockdown of c-FOS or c-JUN abrogated leptin responsiveness. All three MAPKs
      (ERK1/2, JNK1/2, and p38 MAPK) mediated leptin-induced IGF-1 expression. These
      results suggest that leptin contributes to breast cancer progression through the
      transcriptional upregulation of leptin via the MAPK pathway.

PMID- 30293549
TI  - Enhanced Delivery of Protein Fused to Cell Penetrating Peptides to Mammalian
      Cells.
AB  - Recent progress in cellular reprogramming technology and lineage-specific cell
      differentiation has provided great opportunities for translational research.
      Because virus-based gene delivery is not a practical reprogramming protocol,
      protein-based reprogramming has been receiving attention as a safe way to
      generate reprogrammed cells. However, the poor efficiency of the cellular uptake
      of reprogramming proteins is still a major obstacle. Here, we reported key
      factors which improve the cellular uptake of these proteins. Purified red
      fluorescent proteins fused with 9xLysine (dsRED-9K) as a cell penetrating peptide
      were efficiently delivered into the diverse primary cells. Protein delivery was
      improved by the addition of amodiaquine. Furthermore, purified dsRED-9K was able
      to penetrate all cell lineages derived from mouse embryonic stem cells
      efficiently. Our data may provide important insights into the design of protein
      based reprogramming or differentiation protocols.

PMID- 30293550
TI  - Functions of DEAD box RNA helicases DDX5 and DDX17 in chromatin organization and
      transcriptional regulation.
AB  - RNA helicases DDX5 and DDX17 are multitasking proteins that regulate gene
      expression in different biological contexts through diverse activities. Special
      attention has long been paid to their function as coregulators of transcription
      factors, providing insight about their functional association with a number of
      chromatin modifiers and remodelers. However, to date, the variety of described
      mechanisms has made it difficult to understand precisely how these proteins work
      at the molecular level, and the contribution of their ATPase domain to these
      mechanisms remains unclear as well. In light of their association with long
      noncoding RNAs that are key epigenetic regulators, an emerging view is that DDX5
      and DDX17 may act through modulating the activity of various ribonucleoprotein
      complexes that could ensure their targeting to specific chromatin loci. This
      review will comprehensively describe the current knowledge on these different
      mechanisms. We will also discuss the potential roles of DDX5 and DDX17 on the 3D
      chromatin organization and how these could impact gene expression beyond the
      transcriptional and post-transcriptional levels.

PMID- 30293551
TI  - Cellular machinery for sensing mechanical force.
AB  - For mechanical force to induce changes in cellular behaviors, two main processes
      are inevitable; perception of the force and response to it. Perception of
      mechanical force by cells, or mechanosensing, requires mechanical force-induced
      conformational changes in mechanosensors. For this, at least one end of the
      mechanosensors should be anchored to relatively fixed structures, such as
      extracellular matrices or the cytoskeletons, while the other end should be pulled
      along the direction of the mechanical force. Alternatively, mechanosensors may be
      positioned in lipid bilayers, so that conformational changes in the embedded
      sensors can be induced by mechanical force-driven tension in the lipid bilayer.
      Responses to mechanical force by cells, or mechanotransduction, require
      translation of such mechanical force-induced conformational changes into
      biochemical signaling. For this, protein-protein interactions or enzymatic
      activities of mechanosensors should be modulated in response to force-induced
      structural changes. In the last decade, several molecules that met the required
      criteria of mechanosensors have been identified and proven to directly sense
      mechanical force. The present review introduces examples of such mechanosensors
      and summarizes their mechanisms of action.

PMID- 30293552
TI  - [Cow's milk protein allergy with skin lesions. Is it always necessary to refer to
      a dermatologist?]

PMID- 30293553
TI  - Functional Surgery for Malignant Subungual Tumors: A Case Series and Literature
      Review.
AB  - BACKGROUND AND OBJECTIVES: Amputation is the conventional treatment for malignant
      subungual tumors (MSUTs), namely, subungual squamous cell carcinoma (SUSCC) and
      subungual melanoma (SUM). Functional surgery consisting of wide local excision
      (WLE) of the nail unit can preserve function without modifying prognosis in such
      cases. We present a series of MSUTs treated with WLE of the nail unit, describe
      the technique, and review its indications. MATERIAL AND METHODS: Retrospective
      observational study of MSUTs treated with WLE of the nail unit between 2008 and
      2017. The technique consisted of en bloc supraperiosteal excision of the nail
      unit with a margin of 5mm followed by repair with a full-thickness graft.
      RESULTS: Eleven MSUTs were treated in the study period: 7 SUMs (4 in situ; mean
      thickness, 1.17mm; range, 0-4mm) and 4 SUSCCs (mean thickness, 3.4mm; range, 1.6
      6mm). WLE of the nail unit was performed in 9 patients and amputation in 2
      patients with invasive SUM. Mean follow-up was 39 months (range, 12-96 months)
      and no local or regional recurrences were detected. One of the 2 patients who
      underwent amputation developed metastasis to the brain and died. In our review of
      the literature, we identified 5 series of patients with SUSCC treated with WLE of
      the nail unit (105 patients) and 14 series of patients with SUM (243 patients).
      Based on an analysis of these cases and ours, it would appear that WLE of the
      nail unit is associated with a very low rate of local recurrence (<7%) and offers
      better functional and cosmetic outcomes than amputation. CONCLUSIONS: WLE of the
      nail unit is the treatment of choice for SUSCC without bone involvement and for
      thin noninvasive SUM (Breslow depth <1mm). It is also feasible in intermediate
      thickness SUMs when detailed histologic examination of the margins confirms
      complete resection. Amputation, by contrast, is the treatment of choice for
      SUSCCs with bone involvement, very thick SUMs (>4mm), and recurrent tumors.

PMID- 30293554
TI  - Systemic Treatment of Moderate to Severe Psoriasis in Pediatric Patients in
      Galicia, Spain: A Descriptive Study.
AB  - BACKGROUND AND OBJECTIVE: Studies on the use of systemic therapy for psoriasis in
      pediatric patients are scarce. The main aim of this study was to describe the
      systemic treatments used for moderate to severe psoriasis in pediatric clinical
      settings. The second aim was to describe the effectiveness and safety of these
      treatments. MATERIAL AND METHODS: Descriptive, cross-sectional, multicenter study
      of patients under 18 years of age with moderate to severe psoriasis who were
      being treated or had been treated with a systemic drug (conventional or biologic)
      or phototherapy. We recorded demographic and clinical information, treatments
      received, tolerance, adverse effects, and response to treatment. RESULTS: Data
      were collected for 40 patients (60% female; mean age, 13 years) who had received
      63 treatments in total. The most common first treatment (n=40) was phototherapy
      (administered to 68% of patients), followed by acitretin (15%). The most common
      treatments overall (n=63) were phototherapy (57%) and methotrexate (16%). At week
      12 (evaluation of systemic treatment and phototherapy), 66% of the patients were
      classified as good responders and 22% as partial responders. The respective rates
      for week 24 (evaluation of systemic treatment only) were 36% and 32%. The
      treatments were well tolerated (97%) and adverse effects were reported in just
      11% of cases. There were no treatment discontinuations because of adverse
      effects. CONCLUSIONS: Phototherapy, followed by methotrexate, was the most common
      treatment for moderate to severe psoriasis in this series of patients under 18
      years. The treatments showed a favorable safety profile and were associated with
      a good response rate of 66% at week 12 (systemic treatment and phototherapy) and
      36% at week 24 (systemic treatment only).

PMID- 30293555
TI  - Clopidogrel Partially Counteracts Adenosine-5'-Diphosphate Effects on Blood
      Pressure and Renal Hemodynamics and Excretion in Rats.
AB  - BACKGROUND: Adenosine-5'-diphosphate (ADP) can influence intrarenal vascular tone
      and tubular transport, partly through activation of purine P2Y12 receptors (P2Y12
      R), but their actual in vivo role in regulation of renal circulation and
      excretion remains unclear. METHODS: The effects of intravenous ADP infusions of 2
      8mg/kg/hour were examined in anesthetized Wistar rats that were untreated or
      chronically pretreated with clopidogrel, 20mg/kg/24hours, a selective P2Y12-R
      antagonist. Renal blood flow (transonic probe) and perfusion of the superficial
      cortex and medulla (laser-Doppler fluxes) were measured, together with urine
      osmolality (Uosm), diuresis (V), total solute (UosmV), sodium (UNaV) and
      potassium (UKV) excretion. RESULTS: ADP induced a gradual, dose-dependent 15%
      decrease of mean arterial pressure, a sustained increase of renal blood flow and
      a 25% decrease in renal vascular resistance. Clopidogrel pretreatment attenuated
      the mean arterial pressure decrease, and did not significantly alter renal blood
      flow or renal vascular resistance. Renal medullary perfusion was not affected by
      ADP whereas Uosm decreased from 1,080 +/- 125 to 685 +/- 75 mosmol/kg H20. There
      were also substantial significant decreases in UosmV, UNaV and UKV; all these
      changes were attenuated or abolished by clopidogrel pretreatment. Two-weeks'
      clopidogrel treatment decreased V while UosmUosmV and UNaV increased, most
      distinctly after 7 days. Acute clopidogrel infusion modestly decreased mean
      arterial pressure and significantly increased outer- and decreased inner
      medullary perfusion. CONCLUSIONS: Our functional studies show that ADP can cause
      systemic and renal vasodilation and a decrease in mean arterial pressure, an
      action at least partly mediated by P2Y12 receptors. We confirmed that these
      receptors exert tonic action to reduce tubular water reabsorption and urine
      concentration.

PMID- 30293556
TI  - Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative
      Colitis (GETECCU) on the utility of the determination of faecal calprotectin in
      inflammatory bowel disease.
AB  - The management of inflammatory bowel disease (IBD) is currently based on the
      objective evaluation of intestinal lesions. It would therefore be interesting to
      have access to simple and non-invasive tools to monitor IBD activity and to
      identify the presence of lesions. Faecal calprotectin (FC) is the main cytosolic
      protein of neutrophils, it is resistant to bacterial degradation and it is stable
      at room temperature for several days, characteristics that make it suitable for
      use in clinical practice. It can be used to differentiate between inflammatory
      and functional processes, it correlates with endoscopic activity, it is
      associated with clinical and endoscopic response to treatment and it has short
      term prognostic value. This paper offers an up-to-date perspective on the
      information that FC can provide clinicians to aid diagnosis, monitoring and
      management of IBD.

PMID- 30293557
TI  - Hypertension guidelines: How do they apply to kidney transplant recipients.
AB  - Hypertension is common among kidney transplant recipients and may result from
      traditional risk factors or transplant specific variables, which commonly include
      donor associated causes, immunosuppression, or transplant renal artery stenosis.
      Uncontrolled blood pressure in this patient population is associated with
      increased cardiovascular mortality and morbidity, and decreased graft survival.
      Despite these negative associations, there are no randomized controlled trials
      looking at the optimal blood pressure targets and identifying the best
      antihypertensive regimen for this special patient population. Multiple
      hypertension guidelines have been published in the last 10 years, but the Kidney
      Disease: Improving Global Outcomes (KDIGO) and American Society of
      Transplantation (AST) guidelines are the only to recommended a target blood
      pressure in kidney transplant recipients. In this manuscript, we will review the
      available evidence based on randomized clinical trials and large observational
      studies in kidney transplant recipients. Pending new interventional trials, we
      believe that: a) a blood pressure target of <=130/80 is a reasonable goal as
      suggested by KDIGO; b) the choice of antihypertensive agent should be based on
      the patients' other comorbidities; and c) achieving good blood pressure control
      is more important than the choice of the antihypertensive agent; however, the
      initial choice of antihypertensive medications should be calcium channel
      blockers, beta-blockers, diuretics, and angiotensin converting enzyme
      inhibitors/angiotensin receptor blockers as they have all been shown to reduce
      cardiovascular events in the general population.

PMID- 30293558
TI  - Overall and Cause-Specific Mortality of Inflammatory Bowel Disease in Olmsted
      County, Minnesota, From 1970 Through 2016.
AB  - OBJECTIVE: To determine the mortality of Crohn disease (CD) and ulcerative
      colitis (UC) and temporal trends in mortality. PATIENTS AND METHODS: All 895
      residents of Olmsted County, Minnesota, first diagnosed as having inflammatory
      bowel disease (IBD) (411 with CD and 484 with UC) from January 1, 1970, through
      December 31, 2010, were followed through June 30, 2016. Standardized mortality
      ratios (SMRs) were computed-expected rates were derived from the US 2010
      background population. To determine overall and cause-specific mortality, each
      patient with IBD was matched with 5 county residents, and Cox regression analysis
      was used to assess time to death. RESULTS: A total of 895 patients with IBD and
      4475 patients without IBD were included. Seventy-four patients with CD died
      compared with 59.2 expected (SMR, 1.25; 95% CI, 0.98-1.57), and 77 patients with
      UC died compared with 108.1 expected (SMR, 0.71; 95% CI, 0.56-0.89). In CD, the
      risk of dying was significantly associated with diagnosis from 1970 through 1979
      (SMR, 1.90; 95% CI, 1.24-2.78). Of those diagnosed after 1980, the risk of dying
      in patients with CD was similar to the US background population. In UC, the risk
      of dying was less than expected in all periods of diagnosis. In the Cox
      regression analysis, overall mortality was not significantly higher in CD (hazard
      ratio [HR], 1.26; 95% CI, 0.97-1.63) or UC (HR, 0.89; 95% CI, 0.70-1.14) compared
      with the comparison cohort. The risk of dying of digestive diseases (HR, 3.70;
      95% CI, 1.24-11.0) and respiratory diseases (HR, 2.72; 95% CI, 1.36-5.44) was
      increased in CD but not UC. CONCLUSION: In this cohort, overall mortality in
      patients with CD diagnosed after 1980 did not differ from that in the US
      background population. Overall mortality in patients with UC diagnosed from 1970
      through 2010 was lower than the expected mortality.

PMID- 30293561
TI  - Correction.

PMID- 30293559
TI  - Clockwork allergy: How the circadian clock underpins allergic reactions.
AB  - Allergic disease is characterized by marked day-night changes in the clinical
      symptoms and laboratory parameters of allergy. Recent reports suggest that the
      circadian clock, which drives a biological rhythm with a periodicity of
      approximately 24 hours in behavior and physiology, underpins a time of day
      dependent variation in allergic reactions. New studies also suggest that
      disruption of clock activity not only influences temporal variation but can also
      enhance the severity of allergic reactions and even increase susceptibility to
      allergic disease. These findings suggest that the circadian clock is a potent
      regulator of allergic reactions that plays more than a simple circadian
      timekeeping role in allergy. A better understanding of these processes will
      provide new insight into previously unknown aspects of the biology of allergies
      and can lead to the application of clock modifiers to treat allergic disease.
      Finally, this area of research provides a novel opportunity to consider how
      modern lifestyles in the developed world are changing the clinical manifestations
      of allergy as our society quickly transforms into a circadian rhythm-disrupted
      society in which sleeping, working, and eating habits are out of sync with
      endogenous circadian rhythmicity. Such findings might reveal lifestyle
      interventions that enable us to better control allergic disease.

PMID- 30293562
TI  - Is multiple-site colonization with Candida spp. related to inadequate response to
      individualized fluconazole maintenance therapy in women with recurrent Candida
      vulvovaginitis?
AB  - OBJECTIVE: Although most women on fluconazole maintenance therapy for recurrent
      vulvovaginal candidosis experience a substantial improvement in quality of life,
      some do not respond to therapy. Is candidal colonization of extragenital sites
      related to suboptimal response to maintenance therapy? PATIENTS AND METHODS:
      Women included in a multicenter follow-up study (ReCiDiF) were evaluated for
      clinical signs and presence of yeasts in nose, mouth, anus, perineum, and urine.
      Candida was diagnosed by positive microscopy, confirmed by positive culture or
      polymerase chain reaction. After treatment, women were divided into groups
      according to their response to a fluconazole maintenance regimen (optimal,
      suboptimal, and nonresponders). RESULTS: The most frequent extravaginal Candida
      spp. were detected in urine (79.5%), perineum (78.6%), and anus (56.4%). Carriers
      of Candida in the mouth were more likely to have it in the anus (OR 3.2; 95% CI
      1.4-7.7). Colonization in anus (OR 3.3; 95% CI 1.3-8.1) or in multiple
      extravaginal sites (OR 3.0; CI95% 1.2-7.4) was related to nonresponse to therapy.
      Candidal carriage in the anus did not increase anal and perianal symptoms.
      CONCLUSION: Women with anal carriage and multiple-site candidal colonization are
      less likely to respond to individualized decreasing dose fluconazole therapy.

PMID- 30293563
TI  - Myopericarditis with preserved left ventricular function secondary to Neisseria
      meningitidis.
AB  - Cardiac involvement can occur following bacteremia secondary to Neisseria
      meningitidis (Garcia et al. Rev Soc Bras Med Trop. 1999;32(5):517-5122) and is
      likely underrecognized. However, meningococcal disease presenting as primary
      myopericarditis in immunocompetent adults is a relatively rare phenomenon. We
      discuss an unusual presentation of meningococcal disease and the investigation
      and treatment strategies implemented.

PMID- 30293565
TI  - ANKRD9 is associated with tumor suppression as a substrate receptor subunit of
      ubiquitin ligase.
AB  - BACKGROUND: Human ANKRD9 (ankyrin repeat domain 9) expression is altered in some
      cancers. METHODS: We tested genetic association of ANKRD9 with gastric cancer
      susceptibility and examined functional association of ANKRD9 with altered
      proliferation of MKN45 gastric cancer cells. We then identified ANKRD9-binding
      partners in HEK 293 embryonic kidney cells using quantitative proteomics, western
      blotting and complex reconstitution assays. We finally demonstrated ANKRD9's role
      of recognizing substrates for ubiquitination using in vitro ubiquitylation assay.
      RESULTS: ANKRD9 is associated with cancer susceptibility in a comparison of
      single-nucleotide polymorphisms between 1092 gastric cancer patients and 1206
      healthy controls. ANKRD9 depletion accelerates tumor progression by increasing
      cellular proliferation, piling up, and anchorage-independent growth of MKN45
      cells. We discovered that ANKRD9 is a ubiquitin ligase substrate receptor subunit
      and has an anti-proliferative activity. ANKRD9 associates with CUL5 (not CUL2),
      ELOB, ELOC, and presumably RNF7 subunits, which together assemble into a cullin
      RING superfamily E3 ligase complex. ANKRD9 belongs to the ASB family of proteins,
      which are characterized by the presence of ankyrin repeats and a SOCS box. In
      addition to its interactions with the other E3 ligase subunits, ANKRD9 interacts
      with two isoforms of inosine monophosphate dehydrogenase (IMPDH). These IMPDH
      isoforms are cognate substrates of the ANKRD9-containing E3 enzyme, which
      ubiquitinates them for proteasomal degradation. Their ubiquitination and turnover
      require the presence of ANKRD9. CONCLUSION: ANKRD9, a previously unidentified E3
      substrate receptor subunit, functions in tumor suppression by recognizing the
      oncoprotein IMPDH isoforms for E3 ubiquitination and proteasomal degradation.

PMID- 30293566
TI  - PERK inhibition attenuates the abnormalities of the secretory pathway and the
      increased apoptotic rate induced by SIL1 knockdown in HeLa cells.
AB  - Loss-of-function mutations in the SIL1 gene are linked to Marinesco-Sjogren
      syndrome (MSS), a rare multisystem disease of infancy characterized by cerebellar
      and skeletal muscle degeneration. SIL1 is a ubiquitous adenine nucleotide
      exchange factor for the endoplasmic reticulum (ER) chaperone BiP. The complexity
      of mechanisms by which loss of SIL1 causes MSS is not yet fully understood. We
      used HeLa cells to test the hypothesis that impaired protein folding in the ER
      due to loss of SIL1 could affect secretory trafficking, impairing the transport
      of cargoes essential for the function of MSS vulnerable cells. Immunofluorescence
      and ultrastructural analysis of SIL1-knocked-down cells detected ER chaperone
      aggregation, enlargement of the Golgi complex, increased autophagic vacuoles, and
      mitochondrial swelling. SIL1-interefered cells also had delayed ER-to-plasma
      membrane transport with retention of Na+/K+-ATPase and procollagen-I in the ER
      and Golgi, and increased apoptosis. The PERK pathway of the unfolded protein
      response was activated in SIL1-interfered cells, and the PERK inhibitor
      GSK2606414 attenuated the morphological and functional alterations of the
      secretory pathway, and significantly reduced cell death. These results indicate
      that loss of SIL1 is associated with alterations of secretory transport, and
      suggest that inhibiting PERK signalling may alleviate the cellular pathology of
      SIL1-related MSS.

PMID- 30293567
TI  - BRG1 regulates NOX gene transcription in endothelial cells and contributes to
      cardiac ischemia-reperfusion injury.
AB  - Excessive accumulation of reactive oxygen species (ROS) is considered a major
      culprit for a host of cardiovascular diseases. In vascular endothelial cells, ROS
      production is mediated by NAPDH oxidases (NOX). In the present study we
      investigated the role of the chromatin remodeling protein BRG1 in NOX trans
      activation as well as its implication in cardiac ischemia-reperfusion injury. We
      report that in response to hypoxia-reoxygenation (HR) BRG1 was recruited to the
      NOX promoter regions in both immortalized endothelial cells and primary
      microvascular endothelial cells. BRG1 knockdown attenuated the induction of NOX
      genes by HR stimulation. Suppression of NOX trans-activation by BRG1 silencing
      was paralleled by the loss of active histone modifications (acetylation of
      histones H3 and H4) and the re-appearance of repressive histone modification
      (dimethylation of histone H3K9) surrounding the NOX promoter. Of interest, the
      H3K9 demethylase KDM3A bound to the NOX promoters with kinetics similar to BRG1
      and interacted with BRG1 to activate NOX transcription. KDM3A depletion
      ameliorated NOX induction and ROS production in endothelial cells exposed to HR.
      Finally, mice with endothelial-specific deletion of BRG1 were protected from
      cardiac ischemia-reperfusion injury. In conclusion, our data suggest that BRG1
      may link epigenetic activation of NOX transcription in endothelial cells to
      cardiac ischemia reperfusion injury.

PMID- 30293568
TI  - The chromatin remodeling protein BRG1 regulates APAP-induced liver injury by
      modulating CYP3A11 transcription in hepatocyte.
AB  - Acetaminophen (APAP) overdose represents the most frequent cause of acute liver
      failure. The underlying epigenetic mechanism is not fully understood. In the
      present study we investigated the mechanism whereby the chromatin remodeling
      protein brahma related gene 1 (Brg1) regulates APAP induced liver injury in mice.
      We report that hepatocyte-specific deletion of Brg1 attenuated APAP induced liver
      injury in mice as evidenced by reduced plasma ALT and AST levels, decreased liver
      necrosis, amelioration of GSH depletion, and prolonged survival. Brg1 regulated
      APAP-induced liver injury likely by stimulating the transcription of Cyp3a11, a
      key cytochrome enzyme involved in APAP metabolism. Immunoprecipitation coupled
      with DNA affinity microarray identified hepatocyte nuclear factor 4 (HNF4) as a
      novel binding partner for Brg1. HNF4 recruited Brg1 to the Cyp3a11 promoter and
      formed a complex with Brg1 to trans-activate Cyp3a11. In contrast, BRG1
      deficiency attenuated HNF4 binding to the Cyp3a11 promoter and dampened Cyp3a11
      transcription. Therefore, our data suggest that Brg1 might play an essential role
      mediating APAP induced liver injury in vivo.

PMID- 30293569
TI  - Deciphering OPA1 mutations pathogenicity by combined analysis of human, mouse and
      yeast cell models.
AB  - OPA1 is the major gene responsible for Dominant Optic Atrophy (DOA) and the
      syndromic form DOA "plus". Over 370 OPA1 mutations have been identified so far,
      although their pathogenicity is not always clear. We have analyzed one novel and
      a set of known OPA1 mutations to investigate their impact on protein functions in
      primary skin fibroblasts and in two "ad hoc" generated cell systems: the
      MGM1/OPA1 chimera yeast model and the Opa1-/- MEFs model expressing the mutated
      human OPA1 isoform 1. The yeast model allowed us to confirm the deleterious
      effects of these mutations and to gain information on their
      dominance/recessivity. The MEFs model enhanced the phenotypic alteration caused
      by mutations, nicely correlating with the clinical severity observed in patients,
      and suggested that the DOA "plus" phenotype could be induced by the combinatorial
      effect of mitochondrial network fragmentation with variable degrees of mtDNA
      depletion. Overall, the two models proved to be valuable tools to functionally
      assess and define the deleterious mechanism and the pathogenicity of novel OPA1
      mutations, and useful to testing new therapeutic interventions.

PMID- 30293570
TI  - Combined effects of aquaporin-4 and hypoxia produce age-related hydrocephalus.
AB  - Aquaporin-4, present in ependymal cells, in glia limiting and abundantly in
      pericapillary astrocyte foot processes, and aquaporin-1, expressed in choroid
      plexus epithelial cells, play an important role in cerebrospinal fluid production
      and may be involved in the pathophysiology of age-dependent hydrocephalus. The
      finding that brain aquaporins expression is regulated by low oxygen tension led
      us to investigate how hypoxia and elevated levels of cerebral aquaporins may
      result in an increase in cerebrospinal fluid production that could be associated
      with a hydrocephalic condition. Here we have explored, in young and aged mice
      exposed to hypoxia, whether aquaporin-4 and aquaporin-1 participate in the
      development of age-related hydrocephalus. Choroid plexus, striatum, cortex and
      ependymal tissue were analyzed separately both for mRNA and protein levels of
      aquaporins. Furthermore, parameters such as total ventricular volume,
      intraventricular pressure, cerebrospinal fluid outflow rate, ventricular
      compliance and cognitive function were studied in wild type, aquaporin-1 and
      aquaporin-4 knock-out animals subjected to hypoxia or normoxia. Our data
      demonstrate that hypoxia is involved in the development of age-related
      hydrocephalus by a process that depends on aquaporin-4 channels as a main route
      for cerebrospinal fluid movement. Significant increases in aquaporin-4 expression
      that occur over the course of animal aging, together with a reduced cerebrospinal
      fluid outflow rate and ventricular compliance, contribute to produce more severe
      hydrocephalus related to hypoxic events in aged mice, with a notable impairment
      in cognitive function. These results indicate that physiological events and/or
      pathological conditions presenting with cerebral hypoxia/ischemia contribute to
      the development of chronic adult hydrocephalus.

PMID- 30293572
TI  - Adiponectin inhibits hepatic stellate cell activation by targeting the PTEN/AKT
      pathway.
AB  - Adiponectin inhibits hepatic stellate cell (HSC) activation and subsequent
      development of liver fibrosis via multiple mechanisms. Phosphatase and tensin
      homolog deletion 10 (PTEN) plays a crucial role in suppression of HSC activation,
      but its regulation by adiponectin is not fully understood. Here, we investigated
      the effect of adiponectin on PTEN in LX-2 cells, a human cell line and examined
      the underlying molecular mechanisms involved in adiponectin-mediated upregulation
      of PTEN activity during fibrosis. PTEN expression was found to be significantly
      reduced in the livers of mice treated with CCl4, whereas its expression was
      rescued by adiponectin treatment. The DNA methylation proteins DNMT1, DNMT3A, and
      DNMT3B are all highly expressed in activated primary HSCs compared to quiescent
      HSCs, and thus represent additional regulatory targets during liver fibrogenesis.
      Expression of DNMT proteins was significantly induced in the presence of fibrotic
      stimuli; however, only DNMT3B expression was reduced in the presence of
      adiponectin. Adiponectin-induced suppression of DNMT3B was found to be mediated
      by enhanced miR-29b expression. Furthermore, PTEN expression was significantly
      increased by overexpression of miR-29b, whereas its expression was markedly
      reduced by a miR-29b inhibitor in LX-2 cells. These findings suggest that
      adiponectin-induced upregulation of miR-29b can suppress DNMT3B transcription in
      LX-2 cells, thus resulting in reduced methylation of PTEN CpG islands and
      ultimately suppressing the PI3K/AKT pathway. Together, these data suggest a
      possible new explanation for the inhibitory effect of adiponectin on HSC
      activation and liver fibrogenesis.

PMID- 30293571
TI  - Mechanisms underlying modulation of podocyte TRPC6 channels by suPAR: Role of
      NADPH oxidases and Src family tyrosine kinases.
AB  - The soluble urokinase receptor (suPAR) has been implicated in the pathogenesis of
      chronic kidney diseases (CKD) and may function as a circulating "permeability
      factor" driving primary focal and segmental glomerulosclerosis (FSGS). Here we
      examined the mechanisms whereby suPAR causes mobilization and increased
      activation of Ca2+-permeable TRPC6 channels, which are also implicated in FSGS.
      Treatment of immortalized mouse podocytes with recombinant suPAR for 24 h caused
      a marked increase in cytosolic reactive oxygen species (ROS) that required
      signaling through integrins. This effect was associated with increased assembly
      of active cell surface NADPH oxidase 2 (Nox2) complexes and was blocked by the
      Nox2 inhibitor apoycynin. Treatment with suPAR also evoked a functionally
      measurable increase in TRPC6 channels that was blocked by concurrent treatment
      with the ROS-quencher TEMPOL as well as by inhibition of Rac1, an essential
      component of active Nox2 complexes. Elevated ROS evoked by exposing cells to
      suPAR or H2O2 caused a marked increase in the abundance of tyrosine
      phosphorylated proteins including Src, and suPAR-evoked Src activation was
      blocked by TEMPOL. Moreover, mobilization and increased activation of TRPC6 by
      suPAR or H2O2 was blocked by concurrent exposure to PP2, an inhibitor of Src
      family tyrosine kinases. These data suggest that suPAR induces oxidative stress
      in podocytes that in turn drives signaling through Src family kinases to
      upregulate TRPC6 channels. The combination of oxidative stress and altered Ca2+
      signaling may contribute to loss of podocytes and progression of various forms of
      CKD.

PMID- 30293573
TI  - Chemical chaperone 4-phenylbutyric acid alleviates the aggregation of human
      familial pulmonary fibrosis-related mutant SP-A2 protein in part through effects
      on GRP78.
AB  - G231V and F198S mutations in surfactant protein A2 (SP-A2) are associated with
      familial pulmonary fibrosis. These mutations cause defects in dimer/trimer
      assembly, trafficking, and secretion, as well as cause mutant protein
      aggregation. We investigated the effects and mechanisms of chemical chaperones on
      the cellular and biochemical properties of mutant SP-A2. Chemical chaperones,
      including 4-phenyl butyric acid (4-PBA), could enhance secretion and decrease
      intracellular aggregation of mutant SP-A2 in a dose-dependent manner.
      Interestingly, increased levels of aggregated mutant SP-A2, resulting from MG-132
      mediated proteasome inhibition, could also be alleviated by 4-PBA. 4-PBA
      treatment reduced the degradation of mutant SP-A2 to chymotrypsin digestion in
      CHO-K1 cells and up-regulated GRP78 (BiP) expression. Overexpression of GRP78 in
      SP-A2 G231V- or F198S-expressing cells reduced, whereas shRNA-mediated knockdown
      of GRP78 enhanced aggregation of mutant SP-A2, suggesting that GRP78 regulates
      aggregation of mutant SP-A2. Together, these data indicate chemical chaperone 4
      PBA and upregulation of GRP78 can alleviate aggregation to stabilize and
      facilitate secretion of mutant SP-A2. The up-regulation expression of GRP78 might
      partially contribute to the aggregate-alleviating effect of 4-PBA.

PMID- 30293574
TI  - N-methyl-D-aspartate receptor-mediated calcium influx connects amyloid-beta
      oligomers to ectopic neuronal cell cycle reentry in Alzheimer's disease.
AB  - INTRODUCTION: Alzheimer's disease (AD) symptoms reflect synaptic dysfunction and
      neuron death. Amyloid-beta oligomers (AbetaOs) induce excess calcium entry into
      neurons via N-methyl-D-aspartate receptors (NMDARs), contributing to synaptic
      dysfunction. The study described here tested the hypothesis that AbetaO
      stimulated calcium entry also drives neuronal cell cycle reentry (CCR), a prelude
      to neuron death in AD. METHODS: Pharmacologic modulators of calcium entry and
      gene expression knockdown were used in cultured neurons and AD model mice.
      RESULTS: In cultured neurons, AbetaO-stimulated CCR was blocked by NMDAR
      antagonists, total calcium chelation with 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM), or knockdown of the
      NMDAR subunit, NR1. NMDAR antagonists also blocked the activation of calcium
      calmodulin-dependent protein kinase II and treatment of Tg2576 AD model mice with
      the NMDAR antagonist, memantine, prevented CCR. DISCUSSION: This study
      demonstrates a role for AbetaO-stimulated calcium influx via NMDAR and CCR in AD
      and suggests the use of memantine as a disease-modifying therapy for
      presymptomatic AD.

PMID- 30293575
TI  - Consent recommendations for research and international data sharing involving
      persons with dementia.
AB  - Consent is generally required for research and sharing rich individual-level data
      but presents additional ethical and legal challenges where participants have
      diminished decision-making capacity. We formed a multi-disciplinary team to
      develop best practices for consent in data-intensive dementia research. We
      recommend that consent processes for research and data sharing support decision
      making by persons with dementia, protect them from exploitation, and promote the
      common good. Broad consent designed to endure beyond a loss of capacity and
      combined with ongoing oversight can best achieve these goals. Persons with
      dementia should be supported to make decisions and enabled to express their will
      and preferences about participation in advance of a loss of capacity. Regulatory
      frameworks should clarify who can act as a representative for research decisions.
      By promoting harmonization of consent practices across institutions, sectors, and
      countries, we hope to facilitate data sharing to accelerate progress in dementia
      research, care, and prevention.

PMID- 30293576
TI  - Human metabolomics reveal daily variations under nutritional challenges specific
      to serum and skeletal muscle.
AB  - OBJECTIVE: Advances in the field of metabolomics and the concomitant development
      of bioinformatics tools constitute a promising avenue towards the development of
      precision medicine and personalized profiling for numerous disease states.
      Studies in animal models have strengthened this concept, but the application in
      human subjects is scarce. METHODS: Utilizing high-throughput metabolomics, we
      have analyzed the metabolome levels of human serum and skeletal muscle in the
      morning and evening in response to divergent nutritional challenges in order to
      identify unique signatures present in serum and muscle. RESULTS: We reveal
      dynamic daily variation of human metabolome unique to serum and muscle. The
      overall effect of nutritional challenges on the serum and muscle metabolome
      results in a profound rewiring of morning-evening metabolic profiles in human
      participants in response to the timing and type of dietary challenge. CONCLUSION:
      We highlight time-of-day and meal-composition dependence of reprogramming of
      human metabolome by nutritional challenges.

PMID- 30293579
TI  - Implications of the local hemodynamic forces on the formation and destabilization
      of neoatherosclerotic lesions.
AB  - OBJECTIVE: To examine the implications of endothelial shear stress (ESS)
      distribution in the formation of neoatherosclerotic lesions. METHODS: Thirty six
      patients with neoatherosclerotic lesions on optical coherence tomography (OCT)
      were included in this study. The OCT data were used to reconstruct coronary
      anatomy. Blood flow simulation was performed in the models reconstructed from the
      stent borders which it was assumed that represented the lumen surface at
      baseline, immediate after stent implantation, and the estimated ESS was
      associated with the neointima burden, neoatherosclerotic burden and neointima
      characteristics. In segments with neointima rupture blood flow simulation was
      also performed in the model representing the lumen surface before rupture and the
      ESS was estimated at the ruptured site. RESULTS: An inverse association was noted
      between baseline ESS and the incidence and the burden of neoatherosclerotic (beta
      = -0.60, P < 0.001, and beta = -4.05, P < 0.001, respectively) and lipid-rich
      neoatherosclerotic tissue (beta = -0.54, P < 0.001, and beta = -3.60, P < 0.001,
      respectively). Segments exposed to low ESS (<1 Pa) were more likely to exhibit
      macrophages accumulation (28.2% vs 10.9%, P < 0.001), thrombus (11.0% vs 2.6%, P
      < 0.001) and evidence of neointima discontinuities (8.1% vs 0.9%, P < 0.001)
      compared to those exposed to normal or high ESS. In segments with neointima
      rupture the ESS was high at the rupture site compared to the average ESS over the
      culprit lesion (4.00 +/- 3.65 Pa vs 3.14 +/- 2.90 Pa, P < 0.001). CONCLUSIONS:
      Local EES is associated with neoatherosclerotic lesion characteristics, which
      suggests involvement of ESS in the formation of vulnerable plaques in stented
      segments.

PMID- 30293577
TI  - Maternal exercise intervention in obese pregnancy improves the cardiovascular
      health of the adult male offspring.
AB  - OBJECTIVE: Obesity during pregnancy is associated with an elevated risk of
      cardiovascular disease in the offspring. With increased numbers of women entering
      pregnancy overweight or obese, there is a requirement for targeted interventions
      to reduce disease risk in future generations. Using an established murine model
      of maternal obesity during pregnancy, we investigated if a treadmill exercise
      intervention in the mother could improve offspring cardiac health and explored
      potential underlying mechanisms. METHODS: A 20-minute treadmill exercise
      intervention protocol was performed 5 days a week in diet-induced obese female
      C57BL/6 mice 1 week prior to, and up to E17 of pregnancy. All male offspring were
      weaned onto a control diet and studied at 8 weeks of age when their
      cardiovascular physiology was assessed by in vivo echocardiography and non
      invasive tail cuff plethysmography. Cardiomyocyte cell area, re-expression of
      fetal genes and the expression of calcium handling and sympathetic activation
      proteins were determined. RESULTS: At 8 weeks, there was no difference in
      bodyweight or fat mass between groups. Offspring of obese dams developed
      pathologic cardiac hypertrophy, hypertension and cardiac dysfunction
      characterized by reduced ejection fraction (p < 0.001). Maternal exercise
      prevented cardiac hypertrophy and dysfunction but failed to prevent hypertension.
      These offspring of exercised dams also had enhanced (p < 0.001) levels of calcium
      handling proteins and a sympathetic-activated inotropic response. CONCLUSIONS:
      Exercise in obese pregnancy was beneficial to offspring cardiac function and
      structure but did not influence hypertension suggesting they are programmed by
      separate mechanistic pathways. These data suggest combination interventions in
      obese pregnancies will be required to improve all aspects of the cardiovascular
      health of the next generation.

PMID- 30293581
TI  - Message from Dean of Faculty of Medicine, Khon Kaen University.

PMID- 30293580
TI  - Ocular tuberculosis - A closer look to an increasing reality.
AB  - INTRODUCTION: Ocular tuberculosis (OTB) is a rare form of tuberculosis. Diagnosis
      is usually presumptive based on epidemiology, clinical findings and positivity of
      immune response. The aim of the study was to characterize the OTB cases
      identified in Lisbon. METHODS: Retrospective study on OTB cases diagnosed in
      Lisbon from 2012 to 2015. The authors gathered data regarding demographic
      characteristics, diagnostic criteria, type of treatment as well as therapeutic
      results. RESULTS: There were 39 reported cases of presumed OTB which accounted
      for 12.2% of all reported TB cases. Patients had a mean age of 55.5 years. All
      had ocular manifestations (mainly uveitis). Diagnostic criteria included positive
      tuberculin skin test (TST) and/or Interferon Gamma Release Assay (IGRA). Culture
      testing or PCR could not be determined in any patient. Patients had OTB treatment
      for an average of 9.08 months. Clinical improvement was reported in 91.4% of
      treated patients. There were no relapses. CONCLUSION: This is the first published
      series about OTB in Lisbon. All cases had a presumptive diagnosis made through
      TST and/or IGRA testing. Most of treated patients improved, with no signs of
      relapse and a median 29.9-month follow up. OTB seems to be a growing diagnosis
      and treatment may be beneficial even in patients with a presumptive diagnosis.

PMID- 30293583
TI  - Editorial for BBRC lipidomics special issue.

PMID- 30293582
TI  - Message from Permanent Secretary of Public Health.

PMID- 30293584
TI  - The Current Global Reality: Poverty and Income Inequality.
AB  - The distribution of wealth within and between countries is unequal, a reality
      that has preoccupied economists since their discipline's origins. Poverty and
      income inequality are intimately tied to health outcomes, including for pediatric
      neurologic disease. This article provides an overview of the distribution of the
      global poor and global poverty reduction efforts. The emergence of a global
      middle class is discussed, as are issues related to income inequality within
      wealthy nations.

PMID- 30293585
TI  - Global Burden of Pediatric Neurological Disorders.
AB  - Neurological conditions in children represent a significant proportion of the
      global burden of disease, since they contribute to premature mortality and years
      lived with disability. The burden of neurological conditions, as measured by the
      total disability adjusted live years has decreased significantly over the last 25
      years (1990-2015), mainly due to the reduction in the mortality, as the years
      lived with disability has increased slightly. However, in some regions of the
      world, notably South Asia and sub-Saharan Africa, the burden remains high, driven
      by the high incidence of prematurity, neonatal encephalopathy and infections of
      the central nervous system.

PMID- 30293586
TI  - Socioeconomic Status and Pediatric Neurologic Disorders: Current Evidence.
AB  - Socioeconomic status (SES) is an important risk factor for many neurological
      disorders and a determinant of health outcomes and quality of life, especially
      for individuals with neurologic disorders and developmental disabilities. This
      article focuses on the relationship between SES and pediatric epilepsy, cerebral
      palsy, autism spectrum disorder, and intellectual disability. Disparities in the
      prevalence and long-term impact of SES on functioning in persons with
      disabilities are observed worldwide. Clinicians can use the information presented
      in the article to target early identification and interventions for improving
      outcomes in populations most at risk for these disorders and for poor health,
      social, and economic outcomes.

PMID- 30293587
TI  - Imaging Evidence of the Effect of Socio-Economic Status on Brain Structure and
      Development.
AB  - Numerous studies have shown an association between children's socio-economic
      status (SES) and disparities in neurocognitive development, achievements, and
      function later in life. Research focus has recently shifted to imaging of the
      brain's response to the child's environment. This review summarizes the emerging
      studies on the influences of early-life SES on brain structure and development,
      and addresses the relation between brain development and enriched environments.
      The studies provide evidence of significant associations between SES and brain
      structure, growth and maturation, not only in healthy infants and children but
      also in infants with medical conditions. This suggests that the relation between
      SES and later-life function and achievements operates through alterations in
      brain maturation. Although the brain changes seem to persist without
      intervention, animal models of environmental enrichment show the potential of SES
      related brain changes to be reversible and dynamic. This review underscores the
      critical need for reducing the impact of socio-economic disparities and early
      targeted and prolonged interventions, and highlights the potential of these
      interventions leading to optimal opportunities for our youngest.

PMID- 30293588
TI  - A Developmental Social Neuroscience Model for Understanding Pathways to Substance
      Use Disorders During Adolescence.
AB  - Adolescence is a transitional period of development characterized by critical
      changes in physical, neural, cognitive, affective, and social functions. Studies
      investigating the underlying mechanisms of substance use at levels of self
      report, brain response, and behavioral data are generally consistent with
      suggestions from dual-process model that differential growth rates of frontally
      mediated control and striato-frontal reward processing are related to a
      heightened risk of substance use during adolescence. However, social theories
      highlight the important role of social context and environment in which
      adolescents grow up and suggest that growing up in an unfavorable environment and
      in particular exposure to adverse childhood experiences play a huge role in how
      this vulnerability is translated into actual risk. In this review, we provide a
      summary of recent theories that examine a number of key individual and social and
      environmental risk factors underlying risk for early initiation and escalation of
      substance misuse. We also present a model that expands the dual-process model to
      incorporate the role of negative self-concept and negative affect associated with
      growing up in an unfavorable environment and their interactions with cognitive
      control and inhibition to further explain vulnerability to early initiation and
      development of substance misuse in adolescents.

PMID- 30293589
TI  - Justice and Neurodevelopmental Disability: Moral-Political Philosophies,
      Policies, and Their Outcomes.
AB  - Neurodevelopmental disabilities, such as cerebral palsy and autism, touch a
      population which has been dubbed to be "doubly vulnerable." Individuals with
      neurodevelopmental disability have conditions that impair their cognition,
      communication, mobility, or social interactions, and they also rely on others to
      make decisions on their behalf. Accordingly, these children-as described in other
      contributions of this special issue-are particularly prone to suffer from
      systemic (ie, social, economic, and political) conditions that give or prevent
      access to quality and timely health care and social services as well as economic
      opportunities. In this article, we expose 2 different views on the principle of
      justice (justice as equality and justice as fairness). We then examine policy
      approaches and general outcomes of 3 countries (Sweden, the United States of
      America, and the United Kingdom), which have opted for different policy
      orientations. The United Kingdom's targeted approach to neurodevelopmental
      disability seems to be generating interesting results while the more general
      Swedish approach is not without merits, although perhaps more difficult to apply
      to other countries. Given knowledge gaps, there is great need to compare
      different policy approaches to neurodevelopmental disability and their real-world
      implications on the life of individuals and their families.

PMID- 30293590
TI  - Promoting the Human Rights of Children With Neurologic Conditions.
AB  - Children with neurologic conditions benefit from international conventions, and
      national treaties, policies and regulations that safeguard their human rights.
      These regulations also exist to serve as guidance in the creation of
      comprehensive systems of care, inclusive environments, accessible societies and
      communities that allow these children to thrive and to achieve the best of their
      capacities. This narrative review of issues related to human rights and advocacy
      in pediatric neurologic disabilities will provide an overview of the human rights
      conventions that relate to children with disabilities, and the most current
      approaches implicating health care providers in rights promotion for these
      individuals and their families. We also suggest venues for professionals to
      advocate for their patients, and suggest strategies to consider rights-based
      approaches as a mean to provide holistic care in a social neurology framework.

PMID- 30293591
TI  - N-docosahexaenoylethanolamine detected in human breast milk.
AB  - PURPOSE: Measure concentrations of the neurogenic, pro-neurogenic, pro
      synaptogenic and anti-inflammatory mediator N-docosahexaenoylethanolamine
      (synaptamide) in relation to its precursor docosahexaenoic acid (DHA) in breast
      milk. DESIGN AND METHODS: Postpartum women were recruited prior to discharge. We
      supplemented half the subjects with omega-3 fatty acids. Breast milk samples were
      collected at 1, 4 and 8 weeks. Synaptamide and DHA concentrations were determined
      by liquidchromatography/tandem mass spectrometry (LC-MS/MS) and gas
      chromatography, respectively. RESULTS: Synaptamide was detected in all breast
      milk samples. The concentration ranged from 44 to 257 fmol/mL. Omega-3 fatty acid
      supplementation did not affect DHA or synaptamide concentration in breast milk
      due to a high-DHA-containing diet self-selected by control mothers. Nevertheless,
      synaptamide levels significantly correlated with DHA concentration in breast milk
      (r = 0.624, P < 0.001). CONCLUSION: This is the first demonstration of detectable
      concentrations of synaptamide in human breast milk. Although the attempt to raise
      the milk DHA content by omega-3 fatty acid supplementation was not successful in
      the current study, the positive correlation observed between synaptamide and DHA
      concentration suggests that synaptamide levels in human milk can be raised by
      proper omega-3 fatty acid supplementation that is known to increase DHA.

PMID- 30293592
TI  - A stable method for routine analysis of oxylipins from dried blood spots using
      ultra-high performance liquid chromatography-tandem mass spectrometry.
AB  - Oxylipins are biologically important lipid mediators that are derived
      enzymatically from polyunsaturated fatty acids (PUFA) and have a major role in
      regulating inflammatory processes. The currently available methods for measuring
      oxylipins from human biological samples have limitations, which restricts their
      use in large studies. We have developed a novel method for measuring 21 oxylipins
      from dried blood spot (DBS) using ultra-high performance liquid chromatography
      tandem mass spectrometry (UHPLC-MS/MS) and stable isotope dilution analysis. Our
      new method is reproducible and precise and enables the high throughput analysis
      and quantitation of bioactive oxylipins in small volumes of blood. In the future,
      this new method can be readily applied to measure oxylipins in large studies.
      Abstract Oxylipins are downstream lipid mediators enzymatically-produced from
      polyunsaturated fatty acids (PUFA) that are implicated as the biological
      effectors of these fatty acids. Recently reported methods for the quantitation of
      oxylipins require complex extraction procedures. In this study, we report the
      development and validation of a novel system for the quantitation of 21
      individual oxylipins from a dried blood spot (DBS) using ultra-high performance
      liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and stable isotope
      dilution analysis. Linearity and precision of the method were determined and the
      stabilities of the 12 most abundant oxylipins were tested during 2 months of
      storage at room temperature, after being spiked into blood and prepared as DBS on
      PUFAcoatTM paper. Responses were linear across the concentration range analysed
      for all oxylipins (r2 values ranged from 0.953 to 0.998). Intra-day and inter-day
      variations were <=16% for all oxylipins. Recovery of oxylipins from the DBS
      ranged from 80 - 115%. The 12 spiked oxylipins were stable for 2 months when
      stored as DBS at room temperature. Our method is reproducible and precise, and
      provides the opportunity to accurately quantitate these oxylipins in a small
      sample volume.

PMID- 30293593
TI  - Moderating effect of PLIN4 genetic variant on impulsivity traits in 5-year-old
      children born small for gestational age.
AB  - Poor fetal growth is associated with long-term behavioral, metabolic and
      psychiatric alterations, including impulsivity, insulin resistance, and mood
      disorders. However, the consumption of omega-3 polyunsaturated fatty acid (n-3
      PUFA) seems to be protective for this population, improving inhibitory control
      and behavioral reactivity. We investigated whether the presence of the A allele
      of rs8887 SNP (PLIN4 gene), known to be associated with increased sensitivity to
      the consumption of n-3 PUFAs, interacts with fetal growth influencing inhibitory
      control. 152 five-year-old children were genotyped and performed the Stop Signal
      Task (SSRT). There was a significant interaction between birth weight and the
      presence of the A allele on SSRT performance, in which lower birth weight
      associated with poorer inhibitory control only in non-carriers. These results
      suggest that a higher responsiveness to n-3 PUFAS protects small for gestational
      age children from developing poor response inhibition, highlighting that
      optimizing n-3 PUFA intake may benefit this population.

PMID- 30293594
TI  - An overview of the biologic effects of omega-6 oxylipins in humans.
AB  - Oxylipins are lipid mediators produced from polyunsaturated fatty acid (PUFA)
      metabolism, and are thought to be a molecular explanation for the diverse
      biological effects of PUFAs. Like PUFAs, oxylipins are distinguished by their
      omega-6 (n6) or omega-3 (n3) chemistry. We review the use of n6 oxylipins as
      biomarkers of disease and their use in diagnosis and risk assessment. We show
      cases where oxylipins derived from linoleate (LA) or arachidonate (AA) produced
      by the activities of lipoxygenase, cyclooxygenase, epoxygenase, omega/omega-1
      hydroxylase, and autooxidation are useful as biomarkers or risk markers. HODEs,
      KODEs, EpOMEs, DiHOMEs, and other metabolites of LA as well as prostanoids,
      HETEs, KETEs, EpETrEs, and DiHETrEs, and other metabolites of AA were useful for
      understanding the different signaling environments in conditions from traumatic
      brain injury, to major coronary events, dyslipidemia, sepsis, and more. We next
      evaluate interventions that alter the concentrations of n6 oxylipins in plasma.
      We note the utility and response of each plasma fraction, and the generally
      increasing utility from the non-esterified, to the esterified, to the lipoprotein
      fractions. Finally, we review the effects which are specifically related to n6
      oxylipins and most likely to be beneficial. Both n6 and n3 oxylipins work
      together in an exceedingly complex matrix to produce physiological effects. This
      overview should provide future investigators with important perspectives for the
      emerging utility of n6 oxylipins as products of n6 PUFAs in human health.

PMID- 30293595
TI  - Genetic variant in the 3'-untranslated region of the COX2 gene is associated with
      type 2 diabetes: A hospital-based case-control study.
AB  - Type 2 diabetes (T2DM) is caused by the decreased beta-cell mass and insulin
      deficiency, and disease is characterized by hypoglycemia. The insulin resistance
      also plays an important role in T2DM pathogenesis. Insulin resistance is the
      reduced biological response to insulin at the normal concentration in the
      circulation and develops with the influence of environmental factors with genetic
      abnormalities. In recent years, it has been reported that inflammatory pathway
      causes activation of the insulin resistance. Chronic inflammation inhibits the
      insulin sensitivity through activation of signaling pathways which are directly
      associated with the key components of insulin signaling pathway. Cyclooxygenase
      (COX) enzymes are key enzymes that catalysis prostaglandin synthesis from
      arachidonic acid. COX2 is an inducible COX isoform and that plays an important
      role in inflammatory process by leading the synthesis of pro- and anti-
      inflammatory prostaglandins. In our study, we aimed to investigate the
      relationship between variants of COX-2 gene which is one of the key components of
      the inflammatory pathway, and T2DM risks. In this study, we evaluated rs5275 and
      rs689466 variants located on the COX-2 gene by PCR-RFLP in 100 T2DM patients and
      100 control subjects. The interaction among COX2 variants and T2DM was analyzed
      using appropriate methods. The both variants were in Hardy-Weinberg equilibrium
      in patients and controls (p > 0.05). A significant association was observed for
      genotype distribution of COX2 rs5275 site between control and T2DM cases (p =
      0.042). In a dominant model, the cases who had at least one copy of allele C,
      were at increased risk of T2DM (p = 0.016). We found no significant association
      for the COX2 rs689466 domain by evaluating homozygous, heterozygous, dominant,
      and recessive models (p > 0.05). According to our data, the rs5275 variant of the
      COX2 in the 3'-UTR may contribute to the etiology or modulate the risk of T2DM,
      whereas the rs689466 variant of the COX2 gene is not associated with T2DM risk.

PMID- 30293596
TI  - A diet enriched in longer chain omega-3 fatty acids reduced placental
      inflammatory cytokines and improved fetal sustainability of C57BL/6 mice.
AB  - Omega (n)-3 polyunsaturated fatty acids (PUFA) are important regulators of
      inflammatory response that may impact pregnancy outcome. The effects of breeding
      chow diets containing n-3 PUFA from either fish oil (FO) or soybean oil (SO) were
      investigated on tissue fatty acid composition, inflammatory cytokines and
      pregnancy outcome. Female C57BL/6 mice (7 weeks old) were fed FO or SO diets for
      2 weeks before mating and throughout pregnancy. Animals were sacrificed before
      and during pregnancy at day 6.5, 12.5 and 18.5. The FO diet increased the
      incorporation of n-3 PUFA in placenta, with a concomitant decrease in the
      concentration of pro-inflammatory cytokines. The FO diet increased the mRNA
      expression of placental specific PUFA transporter, which coincided with accretion
      of n-3 PUFA in fetal brain. Sites of fetal resorption were noticeable in the SO
      group but not in the FO group. N-3 PUFA may improve fetal sustainability via
      altering cytokine levels.

PMID- 30293597
TI  - Acute fish oil supplementation modulates the inflammatory response after
      strenuous exercise in obese men: A cross-over study.
AB  - AIM: To evaluate the effects of acute fish oil supplementation (FOS) in DNA
      damage, lymphocyte phenotype and cytokines production after strenuous exercise in
      obese individuals. METHODS: Sixteen sedentary obese (BMI >30.0 to <35.0 kg/m2)
      men performed two sessions of exhaustive exercise and consumed 2000 mg of either
      placebo or fish oil one hour before the exercise session; trials were separated
      by 14 days. Peripheral blood mononuclear cells were collected pre, immediately
      after and 1 h after both exercise sessions and stimulated in vitro with 2%
      phytohemagglutinin for cytokines secretion (IL-6, IL-8, TNF-alpha). Analysis of
      DNA damage index on total lymphocytes and the peripheral frequency of T helper
      CD4+ cells, T cytotoxic CD8+ cells, and CD19+ B cells were also performed.
      RESULTS: FOS prevented the increase in serum cortisol levels and the production
      of TNF-alpha and IL-8 after strenuous exercise. The DNA damage index decreased 1
      h after exercise in FOS trial. Moreover, a lymphocytosis, i.e. increases in the
      frequency of CD4+ and CD8+ T cells was observed immediately after exercise bout
      in both trials. Moreover, FOS prevented the decrease in CD8+ T cells below to
      baseline value 1 h after strenuous exercise. CONCLUSION: Acute supplementation
      with fish oil attenuates the proinflammatory cytokine response and diminished the
      DNA damage after strenuous exercise in obese individuals, suggesting a possible
      protective effect against the exacerbation of systemic damage induced by
      exhaustive exercise in obese individuals.

PMID- 30293598
TI  - Full Bayesian conflict-based models for real time safety evaluation of signalized
      intersections.
AB  - Existing advanced traffic management and emerging connected vehicles (CVs)
      technology can generate considerable amount of data on vehicle positions and
      trajectories. This data can be used for real-time safety optimization of
      intersections. To achieve this, it is essential to first understand how changes
      in signal control affect safety in real-time. This paper develops conflict-based
      safety performance functions (SPFs) of signalized intersections at the cycle
      level using multiple traffic conflict indicators. The developed SPFs relate
      various dynamic traffic parameters to the number of rear-end conflicts at the
      signal cycle. The traffic parameters included: queue length, shock wave speed and
      area, and the platoon ratio. The Time-to-Collision, the Modified-Time-to
      Collision, and the Deceleration Rate to Avoid the Crash were used as traffic
      conflict indicators. Traffic video-data collected from six signalized
      intersections was used in the analysis. The SPFs were developed using the Full
      Bayesian approach to address the unobserved heterogeneity and the variation among
      different sites. Overall, the results showed that all the developed SPFs have
      good fit with all explanatory variables being statistically significant. Also,
      the highest conflict frequency was noticed at the beginning of the green time,
      while the highest conflict severity was noticed at the beginning of the red time.
      Lastly, the results can be used most beneficially in real-time safety
      optimization of signalized intersection.

PMID- 30293599
TI  - Ten Steps to Improve Cardiac Arrest Survival in Your Community.
AB  - Creating a system of care for out of hospital cardiac arrest (OHCA) is not a
      simple task. It must be a multifaceted approach that encompasses a variety of
      teams from call takers, to bystanders, to emergency medical service (EMS)
      personnel, to hospital personnel. All of these teams must line up and perform
      their individual task successfully to yield a survivor of OHCA and return a loved
      one to his or her family. Various best practices have been collected and are
      highlighted here. Implementation of these concepts in one's system of care for
      OHCA will not be easy but will result in a greater number of survivors returning
      to their family in the community.

PMID- 30293600
TI  - The Critical Role of Dispatch.
AB  - There are 240 million 9-1-1 calls in the United States every year. The burden of
      managing these emergencies until first responders can arrive is on the
      dispatchers working in the 5806 public safety answering points, more commonly
      known as dispatch centers. They are the first link in the chain of survival
      between the public and the remainder of the health care system. Dispatchers play
      a critical role in the early identification of emergencies, assignment of
      appropriate emergency resources, and provision of life-sustaining interventions
      like dispatcher-assisted cardiopulmonary resuscitation and disaster management.

PMID- 30293601
TI  - Cardiopulmonary Resuscitation Quality Issues.
AB  - Much of the current evidence and many of the recent treatment recommendations for
      increasing survival from cardiac arrest revolve around improving the quality of
      cardiopulmonary resuscitation during resuscitation. A focus on providing
      treatments proved beneficial and providing these treatments reliably, using
      measurement, monitoring, and implementation of quality-improvement strategies,
      will help eliminate variation in outcomes and provide a foundation from which
      future improvements in resuscitation care can be developed. Using the knowledge
      and tools available today will help reduce the ambiguity and variability that
      exists in resuscitation today and provide the ability to save more lives in
      communities.

PMID- 30293602
TI  - Drugs in Out-of-Hospital Cardiac Arrest.
AB  - Managing out-of-hospital cardiac arrest involves unique challenges, including
      delays in the initiation of advanced interventions and a limited number of
      trained personnel on scene. Recent out-of-hospital randomized controlled trials,
      systematic reviews, and metaanalyses provide key insights into what interventions
      are best proven to positively impact patient outcomes from out-of-hospital
      cardiac arrest. We review the literature on medications used in out-of-hospital
      cardiac arrest and summarize evidence-based guidelines from the American Heart
      Association that form the basis for most emergency medical services cardiac
      arrest protocols across the United States.

PMID- 30293603
TI  - Controversial Issues: Pro Mechanical Cardiopulmonary Resuscitation.
AB  - High-quality cardiopulmonary resuscitation, in particular chest compressions, is
      a key aspect of out-of-hospital cardiac arrest (OHCA) resuscitation. Manual chest
      compressions remain the standard of care; however, the extrication and transport
      of patients with OHCA undermine the quality of manual chest compressions and risk
      the safety of paramedics. Therefore, in circumstances whereby high-quality manual
      chest compressions are difficult or unsafe, paramedics should consider using a
      mechanical device. By combining high-quality manual chest compressions and
      judicious application of mechanical chest compressions, emergency medical service
      agencies can optimize paramedic safety and patient outcomes.

PMID- 30293604
TI  - Manual Versus Mechanical Cardiopulmonary Resuscitation: A Case Against the
      Machine.
AB  - Cardiopulmonary resuscitation (CPR) quality, including chest compression rate,
      depth, and fraction of hands-on time, is integral to cardiac arrest survival.
      Introducing mechanized devices to target these measures of quality in the
      challenging prehospital environment holds great promise. Comparing mechanical to
      manual CPR, animal models deliver favorable results on markers of perfusion and
      manikin studies demonstrate improved consistency of high-quality CPR performance
      with device use. Factoring in real-world application with prospective randomized
      human trials; however, repeatedly fails to show improvements in patient-centered
      outcomes and thus cannot be supported by current scientific evidence.

PMID- 30293605
TI  - Double Sequential Defibrillation.
AB  - Ventricular fibrillation (VF) is the most commonly encountered arrhythmia
      following out-of-hospital cardiac arrest. Previous studies have demonstrated
      early defibrillation and bystander cardiopulmonary resuscitation as essential in
      reducing patient mortality. What remains a clinical concern, however, is the
      treatment of patients experiencing VF refractory to defibrillation. Although
      current guidelines advocate pharmacotherapy for the management of shock
      refractory VF, double sequential defibrillation has become a popular topic of
      discussion. This article provides a discourse regarding refractory VF, and a
      review of double sequential defibrillation literature. Further study is required
      before the recommendation for widespread implementation of this defibrillation
      technique.

PMID- 30293606
TI  - Management of Refractory Ventricular Fibrillation (Prehospital and Emergency
      Department).
AB  - Ventricular fibrillation is a life-threatening cardiac arrhythmia that leads to a
      loss of cardiac function and sudden cardiac death. In this review, we summarize
      therapeutic interventions and guidelines for providers managing patients with out
      of-hospital cardiac arrest and refractory ventricular fibrillation in prehospital
      and emergency settings. Additionally, we review invasive management, including
      urgent coronary angiography, extracorporeal membrane oxygenation, and novel
      strategies for managing refractory ventricular fibrillation arrest. Although the
      majority of patients with refractory VF do not respond to conventional therapy,
      recent trials of novel strategies demonstrate encouraging results.

PMID- 30293607
TI  - The Role of Medical Direction in Systems of Out-of-Hospital Cardiac Arrest.
AB  - Survival for out-of-hospital cardiac arrest (OHCA) is, on average, approximately
      10% but considerable variability exists among emergency medical services (EMS)
      systems across the United States. The medical director of an EMS system has
      considerable control and influence over outcomes in a system by developing
      evidence-based protocols and overseeing a robust system of quality assurance. A
      vision for system-level oversight of care that includes continuous data
      collection and assessment, personally delivered and constructive feedback to
      providers, and a constant drive for improvement can result in improvements in
      both processes and patient-centered outcomes.

PMID- 30293608
TI  - Critical Care of the Post-Cardiac Arrest Patient.
AB  - The post-cardiac arrest syndrome is a highly inflammatory state characterized by
      organ dysfunction, systemic ischemia and reperfusion injury, and persistent
      precipitating pathology. Early critical care should focus on identifying and
      treating arrest etiology and minimizing further injury to the brain and other
      organs by optimizing perfusion, oxygenation, ventilation, and temperature.
      Patients should be treated with targeted temperature management, although the
      exact temperature goal is not clear. No earlier than 72 hours after rewarming,
      prognostication using a multimodal approach should inform discussions with
      families regarding likely neurologic outcome.

PMID- 30293609
TI  - Emerging and Future Technologies in Out-of-Hospital Cardiac Arrest Care.
AB  - The care for victims of out-of-hospital cardiac arrest is evolving and will be
      influenced by future and emerging technologies that will play a role in the
      systems of care for these patients. Recent advances in extracorporeal life
      support and point-of-care ultrasound imaging, both in-hospital and out-of
      hospital, may offer a therapeutic solution in some systems for patients with
      refractory or recurrent cardiac arrest. Drones capable of delivering automated
      external defibrillators to the scene of an out-of-hospital cardiac arrest,
      advances in digital and mobile technologies to notify and leverage bystander
      response, and wearable life detection technologies may improve survival.

PMID- 30293610
TI  - A Window into Cutting Edge Prehospital Care of the Cardiac Arrest Patient.

PMID- 30293611
TI  - Increasing complexity of thoracic transplantation and the rise of multiorgan
      transplantation around the world: Insights from the International Society for
      Heart and Lung Transplantation Registry.

PMID- 30293612
TI  - The International Thoracic Organ Transplant Registry of the International Society
      for Heart and Lung Transplantation: Thirty-fifth Adult Heart Transplantation
      Report-2018; Focus Theme: Multiorgan Transplantation.

PMID- 30293613
TI  - The International Thoracic Organ Transplant Registry of the International Society
      for Heart and Lung Transplantation: Thirty-fifth adult lung and heart-lung
      transplant report-2018; Focus theme: Multiorgan Transplantation.

PMID- 30293614
TI  - The International Thoracic Organ Transplant Registry of the International Society
      for Heart and Lung Transplantation: Twenty-first pediatric heart transplantation
      report-2018; Focus theme: Multiorgan Transplantation.

PMID- 30293615
TI  - The International Thoracic Organ Transplant Registry of the International Society
      for Heart and Lung Transplantation: Twenty-first Pediatric Lung and Heart-Lung
      Transplantation Report-2018; Focus Theme: Multiorgan Transplantation.

PMID- 30293616
TI  - Changes in renal function after left ventricular assist device placement in
      pediatric patients: A Pedimacs analysis.
AB  - BACKGROUND: Renal dysfunction (RD) is prevalent among pediatric patients with
      advanced heart failure. Data are limited regarding changes in renal function
      after left ventricular assist device (LVAD) placement in this population.
      METHODS: Pediatric LVAD recipients enrolled in the Pediatric Interagency Registry
      for Mechanical Circulatory Support (Pedimacs) between September 19, 2012 and June
      30, 2016 were included. Longitudinal changes in renal function were analyzed for
      the entire cohort as well as subgroups stratified by patient and device
      characteristics. Logistic regression was used to attempt to identify factors
      associated with lack of improvement in renal function after LVAD placement. Post
      LVAD outcomes were assessed using the Kaplan-Meier method. RESULTS: Data from 247
      patients from 39 centers were analyzed. Baseline RD (estimated glomerular
      filtration rate [eGFR] <90 ml/min/1.73 m2) was present in 150 (61%) patients.
      Overall, eGFR improved post-LVAD, peaking at 1 month post-implant. There was an
      inverse relationship between baseline eGFR and the degree of improvement at 1
      month. Degree of improvement in eGFR at 1 month was not impacted by device type,
      age, Interagency Registry for Mechanically Assisted Circulatory Support
      (INTERMACS) profile, or diagnosis. Failure to normalize renal function at 1 week
      was correlated with persistent RD at 1 month. Post-implant outcomes did not
      differ among patients stratified by pre-implant renal function. CONCLUSIONS:
      Renal function improves post-LVAD placement in pediatric patients regardless of
      age, diagnosis, illness severity, or device type, with improvement most
      pronounced in patients with baseline RD. Identifying patients with irreversible
      renal dysfunction before LVAD placement remains difficult. Pre-LVAD renal
      function does not appear to impact survival to transplant.

PMID- 30293617
TI  - Long-term safety and outcome of intravenous treprostinil via an implanted pump in
      pulmonary hypertension.
AB  - BACKGROUND: We examined safety and long-term outcomes of intravenous treprostinil
      administered via the implantable LENUS Pro pump in patients with severe pulmonary
      hypertension (PH). METHODS: Patients with PH undergoing pump implantation between
      December 2009 and October 2016 in German referral centers were retrospectively
      analyzed (end of follow-up: May 2017). The primary objective was to determine
      long-term safety of the implantable pump. Secondary end points were 3-year
      survival and prognostic relevance of pre-implantation hemodynamics. RESULTS: We
      monitored 129 patients (120 with pulmonary arterial hypertension, 1 with PH due
      to lung diseases, and 8 with inoperable chronic thromboembolic PH) for 260
      patient-years (median follow-up, 19 months; interquartile range, 11-34 months).
      There were 82 complications/peri-procedural events in 60 patients; of these, 57
      were serious adverse events (0.60 per 1,000 treatment-days), including 2
      periprocedural deaths due to right heart failure. The incidence of complications
      related to the pump, catheter, infection, and pump pocket per 1,000 treatment
      days was 0.074, 0.264, 0.032 (3 local infections; no bloodstream infections), and
      0.380, respectively. Three-year overall and transplant-free survival were 66.5%
      and 55.7%, respectively (39 patients died; 16 underwent lung transplantation).
      Baseline cardiac index independently predicted transplant-free survival
      (multivariate hazard ratio, 1.90; 95% confidence interval, 1.11-3.28; p = 0.019;
      n = 95). CONCLUSIONS: Our data suggest that intravenous treprostinil via the
      LENUS Pro pump in advanced PH is associated with a very low risk of bloodstream
      infections, but other serious adverse events may occur. Therefore, this therapy
      needs standardization and should be offered in specialized PH centers only.
      Further technical advances of the pump system and prospective studies are needed.

PMID- 30293618
TI  - Frailty and clinical benefits with lung transplantation.
AB  - BACKGROUND: The Fried frailty phenotype is associated with morbidity and
      mortality in lung transplant (LTx) candidates, but its clinical application and
      association with post-transplant outcomes are not well defined. We assessed 2
      alternate frailty indices in LTx candidates and evaluated associations of frailty
      with early post-transplant outcomes and 1-year mortality. METHODS: Frailty was
      prospectively evaluated in 50 LTx candidates using the Fried and 2 alternate
      phenotypic indices, one using variables readily available to clinicians and one
      using variables from an existing data set. Agreement between indices and
      associations with related measures were assessed to establish validity. The data
      set index was then applied retrospectively to 221 LTx patients. Post-transplant
      outcomes were compared between frail and non-frail patients using t-tests and
      multivariable regression analysis. RESULTS: Frailty prevalence among the 3
      indices was 26% to 30%, and the kappa agreement was 0.38 to 0.41. All indices had
      moderate correlations with London Chest Activity of Daily Living (r = 0.48-0.62)
      and Short-Physical Performance Battery (r = -0.43 to -0.52). In the retrospective
      cohort, frail LTx candidates had a worse St. George's Respiratory Questionnaire
      total score (73 +/- 12vs 62 +/- 12, p < 0.001). Frail candidates had a larger
      improvement with transplant in the St. George's Respiratory Questionnaire (-52 +/
      19vs -43 +/- 18, p = 0.002) and 6-minute walk distance (191 +/- 119vs 129 +/-
      94m, p = 0.001). Frailty was not associated with hospital length of stay or 1
      year mortality. CONCLUSIONS: There was good construct validity and acceptable
      agreement among the frailty indices. Despite significant disability pre
      transplant, frail LTx candidates derived significant benefit with
      transplantation.

PMID- 30293619
TI  - Response by Netuka et al regarding the article "Evaluation of low-intensity anti
      coagulation with a fully magnetically levitated centrifugal-flow circulatory pump
      the MAGENTUM 1 study".

PMID- 30293620
TI  - Value-Added Electrodiagnostics: Targeting Interventions for Fall Risk Reduction.
AB  - Walking confers numerous health benefits, particularly for middle-aged and older
      patients with diabetes and metabolic syndrome. Nevertheless, it brings a risk of
      injurious falls, especially among populations with diabetes and metabolic
      syndrome-related distal neuromuscular decline and frank neuropathy. Those who
      stand to benefit most from walking are at greatest risk. Development of practical
      clinical tools to more precisely quantify neuromuscular function and link it to
      mobility outcomes will help clinicians target interventions toward those at risk
      for falls. Electrodiagnosis, with inclusion of several newer techniques, serves
      as a promising tool for objective evaluation of distal neuromuscular function.

PMID- 30293621
TI  - Detecting Toxic Myopathies as Medication Side Effect.
AB  - The goal of this article is to provide physiatrists, neurologists, and
      neuromuscular medicine physicians a framework that can be easily used in the
      process of evaluating, identifying, and treating patients with toxic myopathies.
      This review attempts to classify these rare but potentially deadly conditions in
      clinical patterns and distinguishes the cellular mechanisms in which the
      offending agents tend to impact the structure and function of myocytes.

PMID- 30293622
TI  - Electrodiagnostic Testing for the Diagnosis and Management of Amyotrophic Lateral
      Sclerosis.
AB  - Electrodiagnostic testing provides insight into subclinical aspects of disease in
      amyotrophic lateral sclerosis and helps to diagnose and exclude other diagnoses.
      It may also help to manage or track disease progression. Mapping the extent of
      subclinical disease may guide the clinician to supportive interventions. There is
      considerable interest in establishing electrodiagnostic biomarkers to monitor
      disease progression. This article details the usefulness of electrodiagnostic
      testing across the disease spectrum. A review of clinical presentations and
      differential diagnoses, diagnostic evaluation, and emerging applications of
      electrodiagnostic studies to guide management and assess response to treatment
      interventions are presented with considerations for clinical practice.

PMID- 30293623
TI  - The Value of Electrodiagnostic Studies in Predicting Treatment Outcomes for
      Patients with Spine Pathologies.
AB  - The utility of electrodiagnostic testing for spine pathologies varies based on
      the underlying suspected pathology. This article reviews the data on
      electrodiagnostic testing for common spine pathologies, with a specific focus on
      the prognostic data with regard to treatment outcomes. This information is placed
      into context of diagnostic confidence, which is derived from the combination of
      disease prevalence and the sensitivity and specificity of a test.

PMID- 30293624
TI  - Planning Interventions to Treat Brachial Plexopathies.
AB  - This article reviews the electrodiagnosis of brachial plexus injury, factors that
      predict outcome, the utility electrodiagnostic evaluation of potential nerve
      donors, and commonly used surgical interventions. Electrodiagnostic evaluation
      begins with a detailed understanding of brachial plexus anatomy and uses a
      complement of motor and sensory nerve conduction studies and needle
      electromyography to determine the location of injury and predict severity.
      Several factors are used to predict prognosis. In injuries with poor prognosis,
      surgical intervention is indicated. Nerve transfers are increasingly employed to
      improve functional outcomes. Electrodiagnosis is key to evaluating the viability
      of potential nerve donors.

PMID- 30293626
TI  - Predicting Recovery from Peripheral Nerve Trauma.
AB  - We enhance the value of electrodiagnostic studies when we discuss prognosis after
      nerve injuries. Nerves are variable in their mechanism, location, and
      pathophysiology of injury. Several factors currently known to influence prognosis
      include the nature of the nerve trauma, amount of axon loss, recruitment in
      muscles supplied by the nerve, extent of demyelination, and distance to
      reinnervate functional muscles. Generally, findings of large motor responses,
      intact recruitment in muscles supplied distal to the injury, and the presence of
      a conduction block are associated with a better prognosis. This article discusses
      nerve-specific information as well.

PMID- 30293625
TI  - Minimizing Risk of Cancer Therapeutics.
AB  - Cancer treatments continue to advance the management and survival of patients.
      However, use of these regimens can lead to significant side effects both
      temporary and permanent. Neuromuscular side effects include chemotherapy-induced
      peripheral neuropathy and radiation fibrosis syndrome. At this time, the only way
      to resolve the neurotoxicity is reduction or discontinuation of the offending
      agent. In an attempt to limit interference with a patient's chemotherapy regimen
      and mitigate chronic disability, efforts for early detection through subjective
      clinical evaluations and objective measurement with electrodiagnostics can help
      to improve symptom management and minimize alteration in treatment.

PMID- 30293627
TI  - Electrodiagnosis in the Patient with Metabolic Syndrome: Adding Value to Patient
      Care.
AB  - Patients with metabolic syndrome are at increased risk of peripheral neuropathy;
      entrapment neuropathies, such as carpal tunnel syndrome; and spine disease that
      can lead to radiculopathy or spinal stenosis. Electrodiagnostic studies are a
      valuable part of patient care in this population. They can confirm suspected
      diagnoses, uncover additional conditions, and lead to the diagnosis of other
      causes of neuropathy that require treatment. By assessing the severity of
      neuropathy, patients at high risk for falls, functional decline, and foot ulcers
      are identified to guide prevention, treatment, and patient education.

PMID- 30293628
TI  - Guiding Treatment for Carpal Tunnel Syndrome.
AB  - Making the correct carpal tunnel syndrome diagnosis is the most important step in
      treatment. Electrodiagnosis can confirm carpal tunnel syndrome and eliminate
      mimicking diseases from the differential. Treatment should provide satisfactory
      pain relief and protection of the median nerve from further deterioration.
      Electrodiagnosis testing provides information on focal median mononeuropathy at
      the wrist that could be used to classify carpal tunnel syndrome from mild to
      severe. The information obtained can help patients to understand and choose
      treatment in a patient-centered fashion. False positives can cause more harm than
      false negatives in the case of carpal tunnel syndrome.

PMID- 30293629
TI  - Steering Peripheral Neuropathy Workup.
AB  - Learning to recognize the various clinical and electrodiagnostic patterns of
      peripheral neuropathy enables a targeted approach to etiologic investigation, and
      subsequently guides patient discussions of self-management, disease course, and
      prognosis. Moreover, as advancements in neuropathology and pharmacotherapy inform
      the many etiologies of polyneuropathy, it is imperative for clinicians to
      identify the underlying etiology to appropriately guide treatment options and
      prevent complications.

PMID- 30293630
TI  - Elucidating the Cause of Pelvic Pain.
AB  - Chronic pelvic pain is a common condition. Establishing a diagnosis can be
      complicated by the interplay between various organ systems, including urologic,
      gynecologic, gastrointestinal, neurologic, endocrinological, psychological, and
      musculoskeletal. Frequently, the patient will have seen multiple providers and
      undergone multiple tests, as well as invasive procedures, before the
      musculoskeletal system is even considered in the differential diagnosis.
      Typically, the musculoskeletal and nervous systems become suspected culprits only
      once all other potential etiologies have been eliminated.

PMID- 30293631
TI  - Guiding Treatment for Foot Pain.
AB  - In the electrodiagnostic (EDX) approach of the patient who presents with foot
      pain, numbness, and/or tingling, it is important to consider a broad differential
      diagnosis of both neuropathic and nonneuropathic conditions, including focal and
      systemic causes. This article assists the electromyographer in the selection and
      utilization of the most appropriate EDX studies for evaluation. The EDX findings
      and impression can then help guide potential treatment options for the patient
      with foot pain and other symptoms. Moreover, this discussion demonstrates the
      added value that EDX evaluation of the foot provides to the comprehensive
      assessment of foot pain.

PMID- 30293632
TI  - Taking Electrodiagnostics a Step Further.

PMID- 30293633
TI  - The Value Electrodiagnosis Adds to Patient Care: Making It Transparent.

PMID- 30293634
TI  - Assessing outpatient follow-up care compliance, complications, and sequelae in
      children hospitalized for isolated traumatic abdominal injuries.
AB  - BACKGROUND: Currently there is limited knowledge on compliance with follow-up
      care in pediatric patients after abdominal trauma. The Indiana Network for
      Patient Care (INPC) is a large regional health information exchange with both
      structured clinical data (e.g., diagnosis codes) and unstructured data (e.g.,
      provider notes). The objective of this study is to determine if regional health
      information exchanges can be used to evaluate whether patients receive all follow
      up care recommended by providers. METHODS: We identified 61 patients treated at a
      Pediatric Level I Trauma Center who were admitted for isolated abdominal
      injuries. We analyzed medical records for two years following initial hospital
      discharge for injury using the INPC. The encounters were classified by the type
      of encounter: outpatient, emergency department, unplanned readmission, surgery,
      imaging studies, and inpatient admission; then further categorized into injury-
      and non-injury-related care, based on provider notes. We determined compliance
      with follow-up care instructions given at discharge and subsequent outpatient
      visits, as well as the prevalence of complications and sequelae. RESULTS: After
      reviewing patient records, we found that 78.7% of patients received all
      recommended follow-up care, 6.6% received partial follow-up care, and 11.5% did
      not receive follow-up care. We found that 4.9% of patients developed
      complications after abdominal trauma and 9.8% developed sequelae in the two years
      following their initial hospitalization. CONCLUSIONS: Our findings suggest that
      health information exchanges such as the INPC are useful in evaluation of follow
      up care compliance and prevalence of complications/sequelae after abdominal
      trauma in pediatric patients. LEVEL OF EVIDENCE: Level IV.

PMID- 30293635
TI  - A statistic to avoid being misled by the "winners curse".

PMID- 30293636
TI  - New-Onset Blistering Eruption in a Young Child.

PMID- 30293637
TI  - Sharing Data to Accelerate Medicine Development and Improve Neonatal Care: Data
      Standards and Harmonized Definitions.

PMID- 30293638
TI  - Factors Associated with Breastfeeding Initiation and Continuation: A Meta
      Analysis.
AB  - OBJECTIVE: To use a quantitative approach to evaluate the literature for
      quantity, quality, and consistency of studies of maternal and infant
      characteristics in association with breastfeeding initiation and continuation,
      and to conduct a meta-analysis to produce summary relative risks (RRs) for
      selected factors. STUDY DESIGN: A systematic review using PubMed and CINAHL
      through March 2016 was conducted to identify relevant observational studies in
      developed nations, reporting a measure of risk for 1 or more of 6 quantitatively
      derived, high impact factors in relation to either breastfeeding initiation or
      continuation. One author abstracted data using a predesigned database, which was
      reviewed by a second independent author; data evaluation and interpretation
      included all co-authors. These factors were summarized using standard meta
      analysis techniques. RESULTS: Six high impact factors were identified (smoking
      [39 papers], mode of delivery [47 papers], parity [31 papers], dyad separation
      [17 papers], maternal education [62 papers], and maternal breastfeeding education
      [32 papers]). Summary RR from random-effects models for breastfeeding initiation
      were highest for high vs low maternal education (RR 2.28 [95% CI 1.92-2.70]),
      dyad connection vs not (RR 2.01 [95% CI 1.38-2.92]), and maternal nonsmoking vs
      smoking (RR = 1.76 [95% CI 1.59-1.95]); results were similar for breastfeeding
      continuation. CONCLUSIONS: Despite methodological heterogeneity across studies,
      relatively consistent results were observed for these perinatally identifiable
      factors associated with breastfeeding initiation and continuation, which may be
      informative in developing targeted interventions to provide education and support
      for successful breastfeeding in more families.

PMID- 30293639
TI  - Understudied and Under-Reported: Fertility Issues in Transgender Youth-A
      Narrative Review.

PMID- 30293640
TI  - Thoraco-Abdominal Abnormalities in Bardet-Biedl Syndrome: Situs Inversus and
      Heterotaxy.
AB  - OBJECTIVES: To characterize the diversity and prevalence of thoraco-abdominal
      abnormalities in Bardet-Biedl syndrome (BBS), a model ciliopathy for
      understanding the role of cilia in human health. STUDY DESIGN: The Clinical
      Registry Investigating BBS, a worldwide registry exploring the phenotype and
      natural history of BBS, was used to conduct the study. Protected health
      information was obtained by subject or family interview and Health Insurance
      Portability and Accountability Act-approved release of data including imaging
      studies and genetic testing. Echocardiography and imaging findings were
      independently confirmed by 2 cardiologists. RESULTS: Thoraco-abdominal
      abnormalities were identified in 6 of 368 (1.6%) subjects with a minimum
      prevalence of 1 in 60 Clinical Registry Investigating BBS participants. Diverse
      laterality defects were observed suggesting that the underlying ciliopathy
      randomly alters embryonic left-right axis orientation. Congenital heart disease,
      common in heterotaxy, was present in 2 subjects. Additional defects, uncommonly
      reported in BBS, were observed in the central nervous, genitourinary,
      gastrointestinal, and musculoskeletal systems in the subjects. No BBS genotype
      was favored in the cohort. One subject had genetic and clinical phenotype
      diagnostic of both primary ciliary dyskinesia and BBS. CONCLUSIONS: The variety
      of thoraco-abdominal abnormalities in BBS suggests the pleiotropic nature of
      these anomalies is not confined to a single pattern or genotype. Clinicians
      providing care to individuals with BBS should consider the increased prevalence
      of thoraco-abdominal anomalies in BBS. Individuals with features suggestive of
      other ciliopathies, such as primary ciliary dyskinesia, should undergo further
      evaluation for additional genetic disorders. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT02329210.

PMID- 30293641
TI  - Risk of Developmental Disorders in Children of Immigrant Mothers: A Population
      Based Data Linkage Evaluation.
AB  - OBJECTIVES: To evaluate the prevalence and risks of developmental disability
      (autism spectrum disorder, intellectual disability, and cerebral palsy) in
      Western Australian children of different groups of foreign-born women. STUDY
      DESIGN: Western Australian population-based linked data of 764 749 singleton live
      births from 1980 to 2010 were used to compare disability outcomes among children
      of foreign-born, Australian-born non-Indigenous, and Indigenous women. The risk
      of disability was assessed using multinomial logistic regression. RESULTS:
      Overall, the prevalence of any disability was lowest for the children of foreign
      born mothers. From 1980 to 1996 but not from 1997 to 2010, children born to
      mothers from foreign-born low-income countries had an increased relative risk of
      autism spectrum disorder with intellectual disability, and children born to
      foreign-born mothers from upper-middle-income countries had an increased risk of
      cerebral palsy with intellectual disability. After adjusting for smoking, the
      relative risks of intellectual disability and cerebral palsy with intellectual
      disability were markedly decreased in children of Australian-born Indigenous
      mothers. CONCLUSIONS: Although we did not find among children born to foreign
      born women an increased prevalence across all the measured developmental
      outcomes, we did observe an increased risk of autism spectrum disorder with
      intellectual disability and cerebral palsy with intellectual disability for
      mothers of some foreign-born groups. Our findings related to smoking in the
      Indigenous population underscore its possible role on the causal pathway to
      intellectual disability. Maternal migration is considered a factor on the causal
      pathway to intellectual disability. Maternal migration may be either a risk or a
      protective factor on the causal pathway to developmental disabilities and the
      direct role of migration is inconclusive in our study.

PMID- 30293642
TI  - Estimating Risk of Pneumonia in a Prospective Emergency Department Cohort.
AB  - OBJECTIVE: To improve the prediction of pediatric pneumonia by developing a
      series of models based on clinically distinct subgroups. We hypothesized that
      these subgroup models would provide superior estimates of pneumonia risk compared
      with a single pediatric model. STUDY DESIGN: We conducted a secondary analysis of
      a prospective cohort being evaluated for radiographic pneumonia in an urban
      pediatric emergency department (ED). Using multivariate modeling, we created 4
      models across subgroups stratified by age and presence of wheezing to predict the
      risk of pneumonia. RESULTS: A total of 2351 patients were included in the study.
      In this series, the prevalence of pneumonia was 8.5%, and 21.6% were
      hospitalized. The highest prevalence of pneumonia was in children aged >2 years
      without wheezing (13.3%). Children aged <2 years with wheezing had the lowest
      prevalence of pneumonia (4.0%). The most accurate model was for children aged <2
      years with wheezing (area under the curve [AUC], 0.80), and the poorest
      performing model was for those aged <2 years without wheezing (AUC, 0.64). The
      AUC of a combination of the 4 subgroup models was 0.76 (95% CI, 0.72-0.80). The
      precision of the models' estimates (expected vs observed) was +/- 3.7%.
      CONCLUSIONS: Using 4 complementary prediction models for pediatric pneumonia, an
      accurate risk of pneumonia can be calculated. These models can provide the basis
      for clinical decision making support to guide the use of chest radiographs and
      promote antibiotic stewardship.

PMID- 30293643
TI  - FMISO-PET-based lymph node hypoxia adds to the prognostic value of tumor only
      hypoxia in HNSCC patients.
AB  - PURPOSE: This secondary analysis of the prospective study on repeat
      [18F]fluoromisonidazole (FMISO)-PET in patients with locally advanced head and
      neck squamous cell carcinomas (HNSCC) assessed the prognostic value of
      synchronous hypoxia in primary tumor (Tu) and lymph node metastases (LN), and
      evaluated whether the combined reading was of higher prognostic value than that
      of primary tumor hypoxia only. METHODS: This analysis included forty-five LN
      positive HNSCC patients. FMISO-PET/CTs were performed at baseline, weeks 1, 2 and
      5 of radiochemotherapy. Based on a binary scale, Tu and LN were categorized as
      hypoxic or normoxic, and two prognostic parameters were defined: Tu-hypoxia
      (independent of the LN oxygenation status) and synchronous Tu-and-LN-hypoxia. In
      fifteen patients with large LN (N = 21), additional quantitative analyses of
      FMISO-PET/CTs were performed. Imaging parameters at different time-points were
      correlated to the endpoints, i.e., locoregional control (LRC), local control
      (LC), regional control (RC) and time to progression (TTP). Survival curves were
      estimated using the cumulative incidence function. Univariable and multivariable
      Cox regression was used to evaluate the prognostic impact of hypoxia on the
      endpoints. RESULTS: Synchronous Tu-and-LN-hypoxia was a strong adverse prognostic
      factor for LC, LRC and TTP at any of the four time-points (p <= 0.004), whereas
      Tu-hypoxia only was significantly associated with poor LC and LRC in weeks 2 and
      5 (p <= 0.047), and with TTP in week 1 (p = 0.046). The multivariable analysis
      confirmed the prognostic value of synchronous Tu-and-LN-hypoxia regarding LRC (HR
      = 14.8, p = 0.017). The quantitative FMISO-PET/CT parameters correlated with
      qualitative hypoxia scale and RC (p < 0.001, p <= 0.033 at week 2, respectively).
      CONCLUSIONS: This secondary analysis suggests that combined reading of primary
      tumor and LN hypoxia adds to the prognostic information of FMSIO-PET in
      comparison to primary tumor assessment alone in particular prior and early during
      radiochemotherapy. Confirmation in ongoing trials is needed before using this
      marker for personalized radiation oncology.

PMID- 30293645
TI  - Foreword to the Free Radical Biology and Medicine Special Issue on Current
      fluorescence and chemiluminescence approaches in free radical and redox biology.

PMID- 30293644
TI  - Complications after stereotactic radiosurgery for brain metastases: Incidences,
      correlating factors, treatments and outcomes.
AB  - BACKGROUND AND PURPOSE: Complications after stereotactic radiosurgery (SRS) for
      brain metastases (BMs) were analyzed in detail using our database including
      nearly 3000 BM patients. MATERIALS AND METHODS: This was an institutional review
      board-approved, retrospective cohort study using our prospectively accumulated
      database including 3271 consecutive patients who underwent gamma knife SRS for
      BMs during the 1998-2016 period. Excluding four patients lost to follow-up, 112
      with three-staged treatment and 189 with post-operative irradiation, 2966 who
      underwent a single-session of SRS only as radical irradiation were studied.
      RESULTS: The overall median survival time after SRS was 7.8 (95% CI; 7.4-8.1)
      months. Post-SRS complications occurred in 86 patients (2.9%) 1.9-211.4 (median;
      24.0, IQR; 12.0-64.6) months after treatment. RTOG neurotoxicity grades were 2, 3
      and 4 in 58, 25 and 3 patients, respectively. Cumulative incidences determined
      with a competing risk analysis were 1.4%, 2.2%, 2.4%, 2.6% and 2.9% at the 12th,
      24th, 36th, 48th and 60th post-SRS month, respectively. Among various pre-SRS
      clinical factors and radiosurgical parameters, multivariable analyses
      demonstrated solitary tumor (Adjusted HR; 0.584, 95% CI; 0.381-0.894, p =
      0.0133), controlled primary cancer (Adjusted HR; 2.595, 95% CI; 1.646-4.091, p <
      0.0001), no extra-cerebral metastases (Adjusted HR; 1.608, 95% CI; 1.028-2.514, p
      = 0.0374), KPS >=80% (Adjusted HR; 2.715, 95% CI; 1.245-5.924, p = 0.0121) and
      largest tumor volume >=3.3 cc (Adjusted HR; 0.516, 95% CI; 0.318-0.836, p =
      0.0072) to be independently significant predictors of a higher incidence of
      complications. CONCLUSION: The post-SRS complication incidence is acceptably low
      (2.9%). Meticulous long-term follow-up after SRS is crucial for all patients.

PMID- 30293646
TI  - Agriculture R&D Implications of the CJEU's Gene-Specific Mutagenesis Ruling.
AB  - On 25 July 2018, the Court of Justice of the European Union (CJEU) ruled that
      gene-specific mutagenesis must be regulated as genetically modified organism
      (GMO) technologies. However, the costs to agricultural research and development
      (R&D) innovation will be staggering, not to mention the brain drain to other
      countries. As a result, Europe can now be known as the deathplace of agricultural
      breeding innovations.

PMID- 30293647
TI  - Perinatal Nutrition and Programmed Risk for Neuropsychiatric Disorders: A Focus
      on Animal Models.
AB  - Maternal nutrition is critically important for fetal development. Recent human
      studies demonstrate a strong connection between diet during pregnancy and
      offspring risk for neuropsychiatric disorders including depression, anxiety, and
      attention-deficit/hyperactivity disorder. Animal models have emerged as a crucial
      tool for understanding maternal nutrition's contribution to prenatal programming
      and the later development of neuropsychiatric disorders. This review highlights
      preclinical studies examining how maternal consumption of the three
      macronutrients (protein, fats, and carbohydrates) influence offspring negative
      valence behaviors relevant to neuropsychiatric disorders. We highlight the
      translational aspects of animal models and so examine exposure periods that
      mirror the neurodevelopmental stages of human gestation. Because of our emphasis
      on programmed changes in neurobehavioral development, studies that continue diet
      exposure until assessment in adulthood are not discussed. The presented research
      provides a strong foundation of preclinical evidence of nutritional programming
      of neurobehavioral impairments. Alterations in risk assessment and response were
      observed alongside neurodevelopmental impairments related to neurogenesis,
      synaptogenesis, and synaptic plasticity. To date, the large majority of studies
      utilized rodent models, and the field could benefit from additional study of
      large-animal models. Additional future directions are discussed, including the
      need for further studies examining how sex as a biological variable affects the
      contribution of maternal nutrition to prenatal programming.

PMID- 30293648
TI  - Use of processing fluids and serum samples to characterize porcine reproductive
      and respiratory syndrome virus dynamics in 3 day-old pigs.
AB  - Collection of serum samples of pigs at weaning to monitor for porcine
      reproductive and respiratory syndrome virus (PRRSV) has become a common practice
      to determine PRRSV herd infection status. Diagnostic sensitivity of this practice
      is low in herds undergoing PRRSV elimination once prevalence of infection is near
      zero. Thus, the goal of this study was to characterize the dynamics of PRRSV
      infection in 3 day-old pigs overtime using serum and serosanguineous fluids
      obtained as part of castration and tail docking practices (processing fluids
      (PF)). Secondary goal was to estimate sensitivity and specificity of PF in the 3
      day old population. A 6000 breed-to-wean sow herd was monitored every three weeks
      for 23 weeks after a PRRSV outbreak by collecting both PF and individual serum
      samples from all pigs in the selected litters. Out of the 77 litters tested, 23
      (29.8%) were identified as positive using the PF and the serum samples, with a
      Cohen's kappa statistic of 0.81 (95% CI: 0.59-1) between the results obtained in
      each sample type. The sensitivity and specificity of the PF relative to the
      results in serum was 87% (95% CI: 66%-97%) and 94% (95% CI: 85%-99%)
      respectively. The percentage of PRRSV positive litters decreased over time and
      litters from gilts were more likely to test positive than those from older sows.
      Overall, the study demonstrates that PF can be a convenient and reliable specimen
      to monitor PRRSV infection in breeding herds.

PMID- 30293649
TI  - Nutrition and oral health.
AB  - To maintain health, the human body needs daily nourishment in the form of
      carbohydrates, proteins and minerals. The associations between oral health
      conditions, dietary practices and nutritional status, and general health status
      are complex with many interrelating factors. Inadequate nutrition can affect the
      oral health including dental caries, periodontal diseases, diseases of oral
      mucosa and infectious diseases. Compromised oral health can alter food choices
      and negatively impact food intake leading to suboptimal nutritional status which
      can lead to chronic systemic diseases. Recognizing and treating oral health and
      nutrition problems are important in improving the health and quality of life.

PMID- 30293650
TI  - Frequency of Complications Including Death from Coronary Artery Bypass Grafting
      in Patients With Hepatic Cirrhosis.
AB  - Advanced liver disease is a risk factor for cardiac surgery. However, liver
      dysfunction is not included in cardiac risk assessment models. We sought to
      identify trends in utilization, complications, and outcomes of patients with
      cirrhosis who underwent coronary artery bypass graft surgery (CABG). Using the
      National Inpatient Sample database, we identified patients with cirrhosis who
      underwent CABG from 2002 to 2014. Propensity-score matching was used to identify
      differences in in-hospital mortality and postoperative complications in cirrhosis
      and noncirrhosis patients. We identified a total of 698,799 CABG admissions of
      which 2,231 (0.3%) had cirrhosis (mean age 63.6 +/- 9.6 years, 74% men, 63%
      white, mean Charlson co-morbidity index 3.3 +/- 1.8). Cardiopulmonary bypass was
      used in 71% of patients. Mean length of stay was 13.7 +/- 11.4 days and
      hospitalization cost $67,744.6 +/- 58,320.4. One or more complications occurred
      in 44% of cases. After propensity-score matching, patients with cirrhosis had a
      higher rate of complications (43.9% vs 38.93%; p < 0.001) and in-hospital
      mortality (7.2% vs 4.07%; p < 0.001) than noncirrhosis patients. On multivariate
      analysis, cirrhosis and ascites were associated with increased in-hospital
      mortality (odds ratio 2.87; 95% confidence intervals 2.37 to 3.48) and
      postoperative complications (odds ratio 5.11; 95% confidence intervals 3.88 to
      6.72). In conclusion, patients with cirrhosis constitute a small portion of
      patients who underwent CABG in the United States but have a higher rate of
      complications and in-hospital mortality compared with noncirrhosis patients. In
      hospital mortality remains high for this subset of patients but has decreased in
      recent years.

PMID- 30293652
TI  - Right-Sided Heart Structural and Functional Remodeling in Mitral Regurgitation
      Secondary to Mitral Valve Prolapse.
AB  - Preoperative evaluation of the mitral valve but also of tricuspid valve and right
      ventricular (RV) function is mandatory in primary mitral regurgitation (MR)
      secondary to mitral valve prolapse (MVP). Tricuspid annulus (TA) diameter plays a
      pivotal role in the surgical decision to perform preventive combined tricuspid
      valve annuloplasty. Cardiac magnetic resonance (CMR) is the gold standard for the
      assessment of RV size and function. Based on 70 consecutive patients (17 women;
      mean age 64 +/- 12) with severe MR secondary to MVP referred for CMR, we sought
      to assess RV geometry and function and TA dimensions and to study the interaction
      between TA dilatation and right-sided cardiac chambers. Frequency of RV
      dilatation, RV systolic dysfunction, and TA dilatation (TA diameter >= 40 or 21
      mm/m2) were 11%, 51%, and 49%, respectively. Left ventricular (LV) end-diastolic
      volume index was the only independent predictor of RV dilatation. Presence of
      symptoms, larger LV end-diastolic volume index, and LV ejection fraction <60%
      were independently associated with RV dysfunction. Absolute TA diameter was 36 +/
      6 mm and TA diameter index was 20 +/- 3 mm/m2. Reproducibility TA diameter
      measurement was excellent (coefficient of variation <=10%). TR velocity >220 cm/s
      (odds ratio = 20.17; [3.57 to 113.90]; p = 0.001 and right atrial volume index >=
      38 ml/m2 (odds ratio = 13.44; [3.57 to 50.54]; p = 0.0001) were independent
      predictors of TA diameter >=40 or 21 mm/m2. CMR provides accurate right-sided
      cardiac chambers assessment and may help surgical planning of concomitant
      tricuspid valve annuloplasty before mitral valve repair in severe MR secondary to
      MVP. In conclusion, TA dilatation, RV enlargement, and dysfunction are related to
      pulmonary pressure and left-sided cardiac chambers enlargement, reflecting the
      long-standing consequences of severe MR.

PMID- 30293651
TI  - Meta-analysis of Prevalence and Risk Factors for Delirium After Transcatheter
      Aortic Valve Implantation.
AB  - Delirium is a severe and common complication following transcatheter aortic valve
      implantation (TAVI). We sought to identify the prevalence and risk factors
      associated with the development of postprocedural delirium in patients aged over
      60 years who underwent elective TAVI for aortic stenosis. Overall, 1,051 articles
      were searched, from which 9 studies were included. The prevalence of delirium
      following TAVI was higher in studies that assessed delirium for a minimum of 3
      consecutive days (24.9%) compared with the studies that did not (2%). There were
      large effect sizes (d > 0.8) for 3 risk factors: acute kidney injury (odds ratio
      [OR] 5, p < 0.001), transapical approach (OR 4, p < 0.001) and carotid artery
      disease (OR 4, p < 0.001), whilst small effect sizes were found for a history of
      atrial fibrillation, prior stroke/transient ischemic attack, peripheral artery
      disease, hypertension, and prior cognitive impairment. In conclusion, 23% of
      patients 60 years and over who underwent TAVI experience delirium, a preventative
      cause of cognitive impairment and dementia. Recognition of risk factors for
      delirium after TAVI, such as a history of carotid artery disease, development of
      acute kidney injury, or use of a transapical approach, provides an opportunity to
      implement proven delirium preventative measures.

PMID- 30293653
TI  - Influence of Baseline Platelet Count on Outcomes in Patients With Venous
      Thromboembolism (from the COMMAND VTE Registry).
AB  - The influence of thrombocytopenia on the long-term clinical outcomes has not been
      thoroughly evaluated in patients with venous thromboembolism (VTE). This study
      sought to elucidate association of baseline thrombocytopenia with bleeding,
      recurrent VTE, and mortality risk. We evaluated the influence of baseline
      thrombocytopenia among 3,012 patients whose baseline platelet counts were
      available in the COMMAND VTE Registry in Japan with a median follow-up period of
      1,219 days. Baseline thrombocytopenia was classified as follows: mild: 100,000 to
      150,000/MUl; moderate: 50,000 to 99,999/MUl; and severe: <50,000/MUl. The primary
      outcome measurement was International Society of Thrombosis and Hemostasis major
      bleeding, and the secondary outcome measurements were recurrent VTE and all-cause
      death. There were 167 patients (5.5%) with moderate or severe thrombocytopenia
      (moderate: 144 patients and severe: 23 patients), 523 patients (17.4%) with mild
      thrombocytopenia, and 2,322 patients (77.1%) without thrombocytopenia. The
      cumulative 5-year incidence of major bleeding was markedly higher in patients
      with moderate or severe thrombocytopenia (moderate or severe 29.4% vs mild: 14.1%
      vs no thrombocytopenia: 10.6%, p <0.001). After adjusting the confounders, the
      risk of or thrombocytopenia relative to no thrombocytopenia for major bleeding
      remained significant (adjusted hazard ratio [HR] 2.15, 95% confidence interval
      [CI] 1.43 to 3.13, p <0.001). The excess risk of moderate or severe
      thrombocytopenia relative to no thrombocytopenia was also significant for
      mortality (adjusted HR 1.54, 95% CI 1.18 to 1.97, p = 0.002), but the risk was
      neutral for recurrent VTE (adjusted HR 1.05, 95% CI 0.55 to 1.81, p = 0.87). In
      conclusion, VTE patients with baseline moderate or severe thrombocytopenia had
      higher risk for major bleeding events and mortality without significant excess
      risk for recurrent VTE events.

PMID- 30293654
TI  - Validation of the 2014 European Society of Cardiology Sudden Cardiac Death Risk
      Prediction Model Among Various Phenotypes in Japanese Patients With Hypertrophic
      Cardiomyopathy.
AB  - Risk stratification for sudden cardiac death (SCD) is essential in the management
      of hypertrophic cardiomyopathy (HC). The 2014 European Society of Cardiology SCD
      risk prediction model (Risk-SCD) is a novel risk scoring system; however, whether
      it can be applied to Japanese HC and its usefulness among various HC phenotypes
      remain unclear. The aim of this study was to validate the Risk-SCD model in
      Japanese HC, and to evaluate its usefulness among various HC phenotypes. We
      studied 370 consecutive Japanese HC patients evaluated for primary SCD prevention
      at our tertiary referral center. The Risk-SCD model was validated in 289 HC
      patients with ejection fraction (EF) >=50% (including left ventricular outflow
      tract obstruction [LVOTO], mid ventricular obstruction [MVO], apical hypertrophy,
      and nonobstructive phenotypes), and 81 end-stage HC patients (EF <50%). The end
      point of the study was SCD or an equivalent event (appropriate implantable
      cardioverter defibrillator therapy or successful resuscitation after cardiac
      arrest). Thirty-one SCD events were observed during a median follow-up of 5.2
      (interquartile range 3.5 to 6.9) years. The Risk-SCD model showed improved risk
      prediction in HC with EF >=50% compared with the previous 2011 American College
      of Cardiology Foundation/American Heart Association and 2003 American College of
      Cardiology/European Society of Cardiology guideline approaches (number needed to
      treat = 3.8 at Risk-SCD >6%) regardless of phenotypes; LVOTO, MVO, apical, and
      nonobstructive, but misclassified SCD risk in end-stage HC. In the current
      external validation of the Risk-SCD model in Japanese HC, the model improved SCD
      prediction compared with previous approaches, and was also shown to be useful in
      LVOTO, MVO, apical, and nonobstructive phenotypes.

PMID- 30293655
TI  - Normalization of N-Terminal Pro-B-Type Natriuretic Peptide After Cardiac Surgery
      Among Children With Tetralogy of Fallot.
AB  - The aim of this study was to temporally measure N-terminal pro-B-type natriuretic
      peptide (NT-proBNP) levels over a period of 18 months after corrective surgery
      among children with tetralogy of Fallot (TOF) and to explore how commonly used
      pharmaceuticals (i.e., spironolactone and digoxin) might affect the normalization
      pattern. This retrospective study included 136 children with a median age of 7
      months who underwent cardiac surgery for TOF. NT-proBNP level was measured at 1,
      3, 6, 12, and 18 months after the surgery. Normalization of NT-proBNP was defined
      as an NT-proBNP level <=250 pg/ml. The commonly used pharmaceuticals
      spironolactone and digoxin after discharge were collected. The normalization
      pattern, normalization time, and potential influence of the pharmaceuticals were
      determined. The rate of normalization was 24.2% (95% confidence interval [CI]
      8.58% to 68.4%) per 100 person-days. Kaplan-Meier survival analysis showed a
      median normalization time of 517 (95% CI 429.6 to 604.3) days. The children whose
      NT-proBNP level did not normalize had a significantly higher readmission rate
      than those whose NT-proBNP level normalized (19.0% vs 2.8%, p = 0.018).
      Multivariable logistic regression models confirmed that the regular users of
      spironolactone, alone (odds ratio = 1.45, 95% CI 1.15 to 1.83) or in combination
      with digoxin (odds ratio = 1.28, 95% CI 1.03 to 1.58), had markedly faster
      recovery trajectories for measures of NT-proBNP than the irregular users of both.
      In conclusion, NT-proBNP normalization after cardiac surgery for TOF is a lengthy
      process, and irregular use of spironolactone could lead to failure in recovery
      and hospital readmission.

PMID- 30293656
TI  - Trends in Incidence, Characteristics, and In-Hospital Outcomes of Patients
      Presenting With Spontaneous Coronary Artery Dissection (From a National
      Population-Based Cohort Study Between 2004 and 2015).
AB  - Though infrequent, spontaneous coronary artery dissection (SCAD) is increasingly
      recognized as an important cause of acute coronary syndrome (ACS), particularly
      in young healthy women. However, the population-based incidence of SCAD is
      unknown. We evaluated the incidence, patient characteristics, clinical
      characteristics, and mortality of SCAD-related hospitalizations using data from a
      national population-based cohort study from January 1, 2004, to September 30,
      2015. In 13,573,200 patients who presented with an acute coronary syndrome,
      66,360 (0.49%) of patients were diagnosed with SCAD. The mean age was 63.1 +/-
      13.2 years and 44.2% were women. In-hospital mortality of SCAD patients was 4.2%:
      5.03% in females and 3.55% in males (p < 0.001). In conclusion, SCAD is an
      uncommon diagnosis that should be considered in males and older patients in
      addition to females presenting with ACS. Most SCAD patients today are managed
      medically. In-hospital mortality is comparable to that of other patients who
      present with ACS.

PMID- 30293657
TI  - Chronic Kidney Disease as a Possible Predictor of Left Atrial Thrombogenic Milieu
      Among Patients with Nonvalvular Atrial Fibrillation.
AB  - Patients with chronic kidney disease (CKD) experiencing atrial arrhythmia are
      hypothesized to have elevated CHADS2 and CHA2DS2-VASc scores, thereby predisposed
      to left atrial (LA) thrombus formation and subsequent thromboembolism. We
      examined possible association of LA thrombogenic milieu (TM) with CKD in patients
      with nonvalvular atrial fibrillation. A total of 581 patients (181 women; mean
      age, 67 years) who underwent transesophageal echocardiography were examined.
      Patients were divided into 4 groups based on the estimated glomerular filtration
      rate (eGFR) (ml/min/1.73 m2): eGFR >=90 (n = 29), 60<= eGFR <90 (n = 329), 30<=
      eGFR <60 (n = 209), and eGFR <30 (n = 14). TM was defined as the presence of LA
      thrombus, dense spontaneous echo contrast, or LA appendage velocity <=25 cm/s. Of
      581 patients, 147 (25%) had TM. The prevalence of TM increased with decreasing
      eGFR (4%, 18%, 36%, and 86% for each group, p <0.001). Similar trends were
      observed for some of the clinical and echocardiographic variables including
      CHA2DS2-VASc score and LA size. Multivariate logistic regression analysis
      revealed that every 10 ml/min/1.73 m2 decrement in eGFR was a significant
      independent correlate of TM (odds ratio 0.80, p = 0.005), along with
      nonparoxysmal atrial fibrillation (AF) (odds ratio 0.45, p = 0.004), higher
      CHA2DS2-VASc score (odds ratio 1.24, p = 0.012), every 5 ml/m2 increment in LA
      volume index (odds ratio 1.57, p <0.001), and every 10% decrement in left
      ventricular ejection fraction (odds ratio 0.51, p <0.001). In conclusion, CKD may
      be a significant risk factor for LA thrombus formation in patients with
      nonvalvular atrial fibrillation.

PMID- 30293658
TI  - Long-Term Left Ventricular Remodeling of Patients With Hypertrophic
      Cardiomyopathy.
AB  - In hypertrophic cardiomyopathy (HC), a process of left ventricular (LV)
      remodeling carrying an adverse prognosis has been described. Conversely, a
      gradual and benign LV wall thinning has been suggested but never investigated.
      Therefore, we studied a HC cohort over a long period of time to evaluate the
      occurrence of a LV remodeling with a benign clinical course. Data of HC patients
      aged 18 to 65 years and without any condition known to influence LV remodeling
      were analyzed over a mean follow-up of 7.6 +/- 5.7 years. Of 231 HC patients (65%
      males, mean age 46 +/- 12 years), 47 (20%) developed LV remodeling, of whom 23
      (10%) had a thinning >=15% of LV maximal wall thickness from baseline without
      systolic dysfunction (MWT thinning); 13 (6%) progressed to a LV ejection fraction
      <50% (end-stage HC) and 11 (5%) developed an apical aneurysm. Follow-up length
      (odds ratio 1.07, 95% confidence interval 1.00 to 1.15, p = 0.06) and maximal LV
      wall thickness at baseline (odds ratio 1.14, 95% confidence interval 1.04 to
      1.25, p = 0.004) were the main predictors of MWT thinning. Compared with patients
      with end-stage HC and apical aneurysm, those with MWT thinning showed lower HC
      related morbidity (92% and 36% vs 22%, p = 0.003) and mortality (31% and 27% vs
      4%, p = 0.02). Furthermore, they showed a combined HC-related morbidity and
      mortality similar to patients without LV remodeling (incidence 29/1000 vs 26/1000
      patient-year, p = 0.77). In conclusion, a process of LV wall thinning with a
      benign outcome can occur over the long term in patients with HC. The prognostic
      importance of LV remodeling varies in relation to the different changes in LV
      morphology and function.

PMID- 30293659
TI  - Diversity of Quaternary Structures Regulates Nuclear Receptor Activities.
AB  - Nuclear receptors (NRs) form homo- and/or heterodimers as central scaffolds of
      multiprotein complexes, which activate or repress gene transcription to regulate
      development, homeostasis, and metabolism. Recent studies on NR quaternary
      structure reveal novel mechanisms of receptor dimerization, the existence of
      tetrameric chromatin-bound NRs, and previously unanticipated protein
      protein/protein-DNA interactions.

PMID- 30293660
TI  - Physiological and biochemical responses of a coralline alga and a sea urchin to
      climate change: Implications for herbivory.
AB  - Direct responses to rising temperatures and ocean acidification are increasingly
      well known for many single species, yet recent reviews have highlighted the need
      for climate change research to consider a broader range of species, how stressors
      may interact, and how stressors may affect species interactions. The latter point
      is important in the context of plant-herbivore interactions, as increasing
      evidence shows that increasing seawater temperature and/or acidification can
      alter algal traits that dictate their susceptibility to herbivores, and
      subsequently, community and ecosystem properties. To better understand how marine
      rocky shore environments will be affected by a changing ocean, in the present
      study we investigated the direct effects of short-term, co-occurring increased
      temperature and ocean acidification on a coralline alga (Jania rubens) and a sea
      urchin herbivore (Echinometra lucunter) and assessed the indirect effects of
      these factors on the algal-herbivore interaction. A 21-day mesocosm experiment
      was conducted with both algae and sea urchins exposed to ambient (24  degrees C,
      Low CO2), high-temperature (28  degrees C, Low CO2), acidified (24  degrees C,
      High CO2), or high-temperature plus acidified (28  degrees C, High CO2)
      conditions. Algal photosynthesis, respiration, and phenolic content were
      unaffected by increased temperature and CO2, but calcium carbonate content was
      reduced under high CO2 treatments in both temperatures, while total sugar content
      of the algae was reduced under acidified, lower temperature conditions. Metabolic
      rates of the sea urchin were elevated in the lower temperature, high CO2
      treatment, and feeding assays showed that consumption rates also increased in
      this treatment. Despite some changes to algal chemical composition, it appears
      that at least under short-term exposure to climate change conditions, direct
      effects on herbivore metabolism dictated herbivory rates, while indirect effects
      caused by changes in algal palatability seemed to be of minor importance.

PMID- 30293661
TI  - Hierarchical structuring of genetic variation at differing geographic scales in
      the cultivated sugar kelp Saccharina latissima.
AB  - The cultivation of macroalgae for biofuels, food and fertilisers has increased
      dramatically in recent years. The demand for such algal-derived products means
      that large scale cultivation in coastal waters will become necessary to provide
      sufficient algal biomass. As part of the process of establishing new macroalgal
      farms, the potential for gene flow between cultivated specimens and natural
      populations needs to be taken into consideration. Consequently, in the present
      study we have used a combined population genetic and hydrodynamic modelling
      approach to determine potential levels and patterns of gene flow in the kelp
      Saccharina latissima. Microsatellite analysis of 14 populations sampled across
      the northern part of the Irish Sea indicated four distinct genetic clusters.
      These were consistent with dispersal patterns indicated by the particle tracking
      model and show a combination of isolation by distance and genetic structuring due
      to local hydrodynamic conditions. At smaller scales (less than a few 10s of km),
      gene flow appears to be fairly extensive, with evidence of local population
      connectivity due to local currents. At larger scales, however, factors such as
      freshwater efflux and open water would appear to represent barriers to gene flow.
      Together, these patterns suggest that factors other than simple geographical
      distance and proximity need to be taken into account when planning the siting of
      kelp farms with the aim of minimizing gene flow to and from natural populations.

PMID- 30293662
TI  - Increased maternal Body Mass Index is associated with congenital heart defects:
      An updated meta-analysis of observational studies.
AB  - PURPOSE: To review and summarize the epidemiologic evidence on the association of
      maternal Body Mass Index (BMI) with risk of congenital heart defects (CHDs) and
      to assess the possible dose-response patterns. METHODS: Six electronic databases
      were searched for eligible studies up to April 2018. The summary risk estimates
      were calculated using either the fixed-effect models or random-effect models. A
      dose-response meta-analysis was also performed to capture the shape of the
      observed association. Subgroup and sensitivity analysis were conducted to explore
      the potential heterogeneity moderators. RESULTS: Twenty-nine studies involving
      99,205 CHDs cases among 6,467,422 participants were included in the meta
      analysis. Mothers who were overweight (odds ratio [OR] = 1.07; 95% confidence
      intervals [CI]: 1.00-1.13) and obese (OR = 1.32; 95% CI: 1.21-1.43) had a
      significantly higher risk of total CHDs in their offspring when compared with
      those with normal weight. When obesity was further divided into class I (OR =
      1.15; 95% CI: 1.11-1.20), class II (OR = 1.26; 95% CI: 1.18-1.34) and class III
      (OR = 1.42; 95% CI: 1.33-1.51) obesity, a significantly increased risk of total
      CHDs persisted. Different risks for specific CHD phenotypes were also found in
      different BMI categories. Furthermore, a nonlinear dose-response relationship
      between maternal BMI and risk of total CHDs was observed. Subgroup and
      sensitivity analyses identified the most relevant heterogeneity moderators.
      CONCLUSION: The increased maternal BMI is associated with the risk of developing
      CHDs in offspring. Severe obesity can play an independent role in the observed
      association, but the effect may be mediated by diabetes mellitus. Preventing
      obesity or excessive weight gain is a priority for CHDs prevention.

PMID- 30293663
TI  - Clinical impact of advanced chronic kidney disease on outcomes and in-hospital
      complications of Takotsubo Syndrome (broken-heart-syndrome): Propensity-matched
      national study.
AB  - Multiple studies evaluated the outcomes and complications rate of Takotsubo
      Syndrome (TTS) in patients with and without advanced chronic kidney disease
      (CKD), revealed conflicting results. This study aims to assess the clinical
      outcomes and impact of advanced CKD on patients hospitalized with Takotsubo
      Syndrome. Patients who presented with Takotsubo cardiomyopathy between 2010 and
      2014 were identified in the National Inpatient Sample (NIS) database using the
      International Classification of Diseases, 9th Revision, Clinical Modification
      (ICD-9-CM), and subsequently were divided into two groups, with advanced CKD and
      without advanced CKD. NIS is the largest all-payer inpatient stays database in
      the United States. The primary outcome was the effect of advanced CKD on
      inpatient mortality in comparison to the non-advanced CKD group. Secondary
      outcomes were the impact of CKD on TTS in-hospital complications. We also
      evaluated the length of hospital stay and the cost of hospitalization. Propensity
      score-matched analysis was performed to address potential confounding. The
      advanced CKD group had no significant increase in the risk of In-hospital
      mortality (OR 0.99; 95% CI 0.75-1.31, P = 0.269). However, advanced CKD patients
      were more likely to develop acute kidney injury (AKI) requiring dialysis (OR:
      5.12, 95% CI: 3.16-8.30, P = <0.0001), and were more likely to stay longer at the
      hospital (OR 1.12; 95% CI 1.03 to 1.22, P 0.010). In conclusion, advanced chronic
      kidney disease does not increase immediate in-hospital mortality, neither most of
      the TTS in-hospital complications, apart from AKI and hospital length of stay, in
      comparison to the patients with non-advanced CKD.

PMID- 30293664
TI  - Late sodium channel blockade improves angina and myocardial perfusion in patients
      with severe coronary microvascular dysfunction: Women's Ischemia Syndrome
      Evaluation-Coronary Vascular Dysfunction ancillary study.
AB  - BACKGROUND: In a prior trial of late sodium channel inhibition (ranolazine) among
      symptomatic subjects without obstructive coronary artery disease (CAD) and
      limited myocardial perfusion reserve index (MPRI), we observed no improvement in
      angina or MPRI, overall. Here we describe the clinical characteristics and
      myocardial perfusion responses of a pre-defined subgroup who had coronary flow
      reserve (CFR) assessed invasively. METHODS: Symptomatic patients without
      obstructive CAD and limited MPRI in a randomized, double-blind, crossover trial
      of ranolazine vs. placebo were subjects of this prespecified substudy. Because we
      had previously observed that adverse outcomes and beneficial treatment responses
      occurred in those with lower CFR, patients were subgrouped by CFR <2.5 vs >=2.5.
      Symptoms were assessed using the Seattle Angina Questionnaire and the SAQ-7, and
      left-ventricular volume and MPRI were assessed by magnetic resonance imaging
      (MRI). Coronary angiograms, CFR, and MRI data were analyzed by core labs masked
      to treatment and patient characteristics. RESULTS: During qualifying coronary
      angiography, 81 patients (mean age 55 years, 98% women) had invasively determined
      CFR 2.69 +/- 0.65 (mean +/- SD; range 1.4-5.5); 43% (n = 35) had CFR <2.5.
      Demographic and symptomatic findings did not differ comparing CFR subgroups.
      Those with low CFR had improved angina (p = 0.04) and midventricular MPRI (p =
      0.03) with ranolazine vs placebo. Among patients with low CFR, reduced left
      ventricular end-diastolic volume predicted a beneficial angina response.
      CONCLUSIONS: Symptomatic patients with CFR <2.5 and no obstructive CAD had
      improved angina and myocardial perfusion with ranolazine, supporting the
      hypothesis that the late sodium channel is important in management of coronary
      microvascular dysfunction. TRIAL REGISTRATION: clinicaltrials.gov Identifier
      NCT01342029.

PMID- 30293665
TI  - Impact of increasing dose of intracoronary adenosine on peak hyperemia duration
      during fractional flow reserve assessment.
AB  - BACKGROUND: Fractional Flow Reserve (FFR) is currently indicated as a first line
      strategy for the functional assessment of intermediate coronary stenoses.
      However, the protocol for inducing hyperemia still lacks standardization.
      Intracoronary adenosine boli, with a progressive increase to high-dosage, have
      been proposed as a sensitive and accurate strategy for the classification of
      coronary stenoses, although being potentially affected by the achievement of
      plateau of the effect and by a less prolonged and stable hyperemia as compared to
      intravenous administration. Therefore, the aim of the present study was to define
      the conditioning parameters and assess the impact of increasing-dose
      intracoronary adenosine on peak hyperemia duration in patients undergoing FFR for
      intermediate coronary stenoses. METHODS: FFR was assessed in patients with
      intermediate (40 to 70%) lesions by pressure-recording guidewire (Prime Wire,
      Volcano), after induction of hyperemia with intracoronary boli of adenosine (from
      60 to 1440 MUg, with dose doubling at each step). Hyperemic duration was defined
      as the time for the variation form minimum FFR +/- 0.02 and time to recovery till
      baseline values. RESULTS: We included 87 patients, undergoing FFR evaluation of
      101 lesions. Mean peak hyperemia duration and time to recovery significantly
      increased with adenosine doses escalation (p = 0.02 and p < 0.001). Peak
      hyperemia duration and time to recovery with 1440 MUg adenosine were 14.5 +/-
      12.6 s and 45.2 +/- 30.7 s, respectively. Hyperemia duration was not related to
      Quantitative Coronary Angiography (QCA) parameters or FFR values. In fact, a
      similar increase in the time of hyperemic peak was noted when comparing patients
      with positive or negative FFR (pbetween = 0.87) or patients with lesions < or
      >=20 mm (pbetween = 0.92) and lesions involving left main coronary or proximal
      left anterior descending artery (LAD) (pbetween = 0.07). A linear relationship
      was observed between time to recovery and FFR variations, with a greater time to
      baseline required in patients with FFR <= 0.80 (p = 0.003) and in lesions >= 20
      mm (p = 0.006), but not in LAD/LM lesions (p = 0.55). CONCLUSIONS: The present
      study shows a progressive raise in the duration of peak hyperemia and time to
      recovery, after the administration of increasing doses of intracoronary adenosine
      for the assessment of FFR. Therefore, considering the potential advantages of a
      high-dose adenosine protocol, allowing a more prolonged hyperemia and a more
      precise and reliable measurement of FFR, further larger studies with such FFR
      strategy should certainly be advocated to confirm its safety and benefits, before
      its routinely use recommendation.

PMID- 30293666
TI  - Impact of angiographic coronary artery disease complexity on ischemic and
      bleeding risks and on the comparative effectiveness of zotarolimus-eluting vs.
      bare-metal stents in uncertain drug-eluting stent candidates.
AB  - BACKGROUND: The impact of coronary artery disease (CAD) extension/complexity on
      outcomes and on the comparative benefits/risks of zotarolimus-eluting stent (ZES)
      versus bare-metal stents (BMS) remains unclear in patients at high risk of
      bleeding or thrombosis or at low restenosis risk. METHODS: We performed a post
      hoc analysis of the ZEUS trial. The impact of coronary anatomic complexity
      measured by the SYNTAX score on the differences in outcomes following ZES and BMS
      was assessed at 1 year. RESULTS: The mean SYNTAX score was 16.3 +/- 13.1 with a
      median of 12 (IQR: 7 to 22). We stratified patients according to SYNTAX tertiles
      (0-8: n = 563; >8-19 n = 532; >19: n = 511), and observed that the higher the
      score, the correspondingly higher was the rate of the primary endpoint of major
      adverse cardiovascular events (MACE) and other ischemic events, but not bleeding
      after adjustment. The superior efficacy of ZES versus BMS for MACE was consistent
      across SYNTAX tertiles (tertile 1: HR 0.71, 95% CI 0.44-1.13; tertile 2: HR 0.71,
      95% CI 0.46-1.09; tertile 3: HR 0.83, 95% CI 0.61-1.10) without significant
      heterogeneity (p for trend = 0.55). This between-groups difference mainly
      reflected a reduction in MI and TVR without effect on mortality. There was no
      significant interaction between the SYNTAX score and allocated stent type with
      respect to ischemic and bleeding endpoints. CONCLUSIONS: The SYNTAX score was
      predictor of major adverse cardiovascular events but not bleeding and ZES
      provided superior efficacy and safety than BMS across the whole spectrum of CAD
      complexity. SYNTAX score may be routinely used for the assessment of the ischemic
      risk (but not bleeding) after PCI and should not guide the decision-making for
      DES versus BMS in patients undergoing PCI.

PMID- 30293667
TI  - ECG left ventricular hypertrophy as a risk predictor of sudden cardiac death.
AB  - BACKGROUND: Electrocardiographic (ECG) left ventricular hypertrophy (LVH) is an
      established risk factor for cardiovascular events. However, limited data is
      available on the prognostic values of different ECG LVH criteria specifically to
      sudden cardiac death (SCD). Our goal was to assess relationships of different ECG
      LVH criteria to SCD. METHODS: Three traditional and clinically useful (Sokolow
      Lyon, Cornell, RaVL) and a recently proposed (Peguero-Lo Presti) ECG LVH voltage
      criteria were measured in 5730 subjects in the Health 2000 Survey, a national
      general population cohort study. Relationships between LVH criteria, as well as
      their selected composites, to SCD were analyzed with Cox regression models. In
      addition, population-attributable fractions for LVH criteria were calculated.
      RESULTS: After a mean follow-up of 12.5 +/- 2.2 years, 134 SCDs had occurred.
      When used as continuous variables, all LVH criteria except for RaVL were
      associated with SCD in multivariable analyses. When single LVH criteria were used
      as dichotomous variables, only Cornell was significant after adjustments. The
      dichotomous composite of Sokolow-Lyon and Cornell was also significant after
      adjustments (hazard ratio for SCD 1.82, 95% confidence interval 1.20-2.70, P =
      0.006) and was the only LVH measure that showed statistically significant
      population-attributable fraction (11.0%, 95% confidence interval 1.9-19.2%, P =
      0.019). CONCLUSIONS: Sokolow-Lyon, Cornell, and Peguero-Lo Presti ECG, but not
      RaVL voltage, are associated with SCD risk as continuous ECG voltage LVH
      variables. When SCD risk assessment/adjustment is performed using a dichotomous
      ECG LVH measure, composite of Sokolow-Lyon and Cornell voltages is the preferred
      option.

PMID- 30293668
TI  - The asymmetry of dermatoglyphic finger ridge counts and the geographic altitude
      of the Jujenean population in northwest Argentina.
AB  - Asymmetry is omnipresent in the living world and therefore is a measure of
      developmental noise and instability. The main stressing agent in high-altitude
      ecosystems is hypobaric hypoxia. The variation in bilateral dermatoglyphic
      symmetry in populations from the Province of Jujuy in northwest Argentina is
      analyzed, and these results are compared to those for other populations with
      different ethnic and environmental backgrounds. Fingerprints were collected from
      310 healthy students (140 males and 170 females) aged 18-20 years from three
      localities in Jujuy Province-Abra Pampa (3484 m above sea level), Humahuaca (2939
      m above sea level), and San Salvador de Jujuy (1260 m above sea level). Asymmetry
      by sex was assessed based on radial and ulnar ridge counts to determine its
      pattern of variability (directional asymmetry [DA], fluctuating asymmetry [FA]
      and antisymmetry), and asymmetry and diversity indices were calculated. A
      bivariate plot and principal component analysis (PCA) were used to compare these
      indices with those for other populations. Homogeneity was found between
      populations and sexes when radial and ulnar ridges were counted. FA values did
      not show significant differences by locality or side (ulnar and radial), but
      significant differences were found by finger and sex, with males showing
      significantly greater FA values. The asymmetry and diversity indices clearly
      group the Andean populations and separate them from populations of different
      ethnic and geographic origin. Only the diversity index showed significant
      differences by locality in males, which suggests a substantially different
      genetic component in Abra Pampa male samples.

PMID- 30293669
TI  - Psychosocial Health and Lifestyle Behaviors in Young Adults Receiving Renal
      Replacement Therapy Compared to the General Population: Findings From the SPEAK
      Study.
AB  - RATIONALE & OBJECTIVE: Patients in late adolescence and early adulthood receiving
      renal replacement therapy (RRT) face disruption to normal activities, which
      affects well-being. We aimed to define psychosocial and lifestyle outcomes for
      young adults on RRT compared to the general population. STUDY DESIGN: We
      undertook a cross-sectional survey (the SPEAK [Surveying Patients Experiencing
      Young Adult Kidney Failure] Study) using validated measures and general
      population comparator data from the Health Survey for England and Avon
      Longitudinal Study of Parents and Children. Additional clinical information was
      obtained from the UK Renal Registry. SETTING & PARTICIPANTS: 16- to 30-year-olds
      receiving RRT. OUTCOMES: Psychosocial health and lifestyle behaviors. ANALYTICAL
      APPROACH: We compared outcomes between populations using age- and sex-adjusted
      regression models, weighted to account for response bias by sex, ethnicity, and
      socioeconomic status. Our findings were used to update recent meta-analyses.
      RESULTS: We recruited 976 young adults and 64% responded to the survey: 417 (71%)
      with kidney transplants and 173 (29%) on dialysis therapy. Compared to the
      general population, young adults on RRT were less likely to be in a relationship
      and have children and more likely to live in the family home, receive no income,
      and be unable to work due to health. They had poorer quality of life, worse well
      being, and twice the likelihood of a psychological disturbance (OR, 2.7; 95% CI,
      2.0-3.7; P<0.001). They reported less smoking, alcohol and drug abuse, and crime.
      In a meta-analysis, our study showed the greatest differences in quality of life
      compared to the general population. LIMITATIONS: Cross-sectional study design,
      meaning that we could not track the impact of treatment changes on the outcomes.
      CONCLUSIONS: This study involving a large cohort of young adult transplant
      recipients and dialysis patients provides evidence of worse psychosocial outcomes
      but more positive lifestyle behaviors in young adults on RRT compared to the age
      matched general population.

PMID- 30293670
TI  - Finding fibroblast growth factor 19 during cholestasis: Does x mark the spot?

PMID- 30293671
TI  - Venous-arterial CO2 to arterial-venous O2 differences: A physiological meaning
      debate.

PMID- 30293672
TI  - Transcriptome analysis of the midgut gland of the brown shrimp Crangon crangon
      indicates high polymorphism in digestive enzymes.
AB  - Tolerance of organisms towards heterogeneous and variable environments is highly
      related to physiological flexibility. An effective strategy to enhance
      physiological flexibility is the expression of polymorphic enzymes. This seems to
      be the case in the brown shrimp Crangon crangon. It shows high reproduction
      rates, feeds opportunistically on endo- and epibenthic organisms, and is
      apparently well adapted to variable environmental conditions. Previous
      electrophoretic studies revealed a high level of polymorphism and no consistent
      phenotype of digestive enzymes between individuals. In order to understand the
      underlying biochemical processes, we carried out a transcriptome-based study of
      digestive enzymes of C. crangon. Detailed sequence analyses of triacylglycerol
      lipase, phospholipase A2, alpha amylase, chitinase, trypsin and cathepsin L were
      performed to identify putative isoforms. The number of isoforms, and thus the
      degree of polymorphism varied among enzymes: lipases and carbohydrases showed
      higher numbers of isoforms in enzymes that besides their extracellular function
      also have diverse intracellular functions. Furthermore, cysteine proteinases
      showed a lower polymorphism than serine proteinases. We suggest that the
      expression of enzyme isoforms improves the efficiency of C. crangon in gaining
      energy from different food sources.

PMID- 30293673
TI  - Transcriptomic and metabolic response to chronic and acute thermal exposure of
      juvenile geoduck clams Panopea globosa.
AB  - The Cortes geoduck Panopea globosa is a large bivalve with a high commercial
      value distributed from the southern Pacific coast of the Baja California
      Peninsula to the northern Gulf of California, inhabiting a wide range of
      subtropical temperatures. A new record of this species in shallower waters
      suggests that it can tolerate a warmer environment than previously thought. To
      better understand the whole-body and molecular response mechanisms to different
      temperatures, we assessed the metabolic rate of juvenile individuals exposed to
      chronic and acute thermal conditions and analyzed the transcriptomic response in
      ctenidial tissues. Whole-body metabolic rate measurements showed that juveniles
      were able to acclimate at least partially within three weeks from 20  degrees C
      (C20) to 29  degrees C (C29), while organisms acutely exposed to 29  degrees C
      (A29) significantly increased their metabolic rate. This was coincident with
      transcriptomic results, as similar gene expression patterns were found in clams
      chronically exposed to C29 and C20, but different from those acutely exposed to
      29  degrees C (A29) and 31  degrees C (A31). High degree of expression of genes
      involved in DNA repair and transcription regulation were found in C29 juveniles,
      whereas protective genes against oxidative stress were highly expressed in A29
      organisms. A high expression of genes involved in protein re-folding was also
      observed in A31 juveniles. In conclusion, the combined results of whole-body
      metabolism and transcriptomic expression patterns suggest that P. globosa
      juveniles have a high physiological plasticity and are well adapted to inhabit an
      environment with broad temperature fluctuations.

PMID- 30293674
TI  - Triple therapy: A review of antithrombotic treatment for patients with atrial
      fibrillation undergoing percutaneous coronary intervention.
AB  - In patients with atrial fibrillation (AF), concomitant coronary artery disease is
      often present, and vice versa. Optimal antithrombotic treatment for patients with
      AF undergoing percutaneous coronary intervention (PCI) is one of the major
      concerns in the field of cardiology. Triple therapy, a combination of oral
      anticoagulant (OAC) plus dual antiplatelet therapy with aspirin and P2Y12
      inhibitor, has been used for patients with AF undergoing PCI in recent decades to
      reduce ischemic events under guideline recommendations. However, triple therapy
      is well-known to induce severe bleeding events. Recently, the results of several
      clinical trials have been published, and the latest guidelines recommend that
      most patients should undergo dual therapy (i.e. OAC plus P2Y12 inhibitor) from
      the beginning of PCI, or triple therapy only peri-PCI period and immediately
      shift to dual therapy after hospital discharge. Although these recommendations
      are useful and appear to be reasonable, no studies have validated this. In
      addition, there are a number of unresolved issues regarding the antithrombotic
      treatment for patients with AF undergoing PCI such as risk prediction models and
      the best combination of OAC with antiplatelet agents, and prospective trials are
      ongoing. This review article will summarize current evidence and focus on the
      optimal regimen of antithrombotic treatment for patients with AF undergoing PCI.

PMID- 30293676
TI  - Safety of fertility preservation in women with breast cancer.

PMID- 30293675
TI  - Silicosis: A former occupational disease with new occupational exposure
      scenarios.
AB  - BACKGROUND: Recent studies have shown an increase in the prevalence of silicosis
      due to the use of artificial quartz aggregates (AQA). The aim of this study was
      to assess the cases of silicosis in our area reported to the Healthcare
      Information System for Occupational Epidemiological Surveillance of the
      Autonomous Community of Valencia to detect new agents of exposure to silica and
      working conditions that promote its onset. MATERIAL AND METHOD: A descriptive
      study was conducted of cases of silicosis reported to the Healthcare Information
      System for Occupational Epidemiological Surveillance of the Autonomous Community
      of Valencia from January 2009 to September 2016. The data sources include
      epidemiological-occupational surveys and medical reports. RESULTS: Nineteen cases
      of silicosis were reported, 74% of which were diagnosed using high-resolution
      computed tomography. Some 68.4% of the cases were related to the handling of AQA,
      as assemblers/cutters/sanders of countertops. The subgroup's mean age was 46.62+/
      13.33 years, and the mean exposure was 11.00+/-3.58 years. The rest of the
      patients worked in companies with no AQA exposure, with a mean age of 62.33+/
      16.22 years and a mean exposure of 27.16+/-8.44 years (P<.05). Four cases
      presented complicated forms (3 exposed to AQA). CONCLUSIONS: The work of
      assembling/cutting/sanding AQA countertops presents a high risk of developing the
      disease. The mean age at onset and the exposure time for this group is lower, and
      the percentage of complicated clinical forms is higher. Improvements need to be
      made in preventive planning for companies with exposure to these new agents.

PMID- 30293677
TI  - Activity of fixed direct electrical current in experimental Staphylococcus aureus
      foreign-body osteomyelitis.
AB  - Fixed DC was compared to ceftriaxone, ceftriaxone with 200 MUA fixed DC, or no
      treatment in a rat model of methicillin-susceptible Staphylococcus aureus foreign
      body osteomyelitis. After 3 weeks, fewer bacteria were present in bones of the
      ceftriaxone group (5.71 log10cfu/g [P = 0.0004]) and the ceftriaxone/DC group
      (3.53 log10cfu/g [P = 0.0002]) than untreated controls (6.70 log10cfu/g). Fewer
      bacteria were present in the ceftriaxone/DC group than in the ceftriaxone-alone
      and DC-alone groups (P = 0.0012 and 0.0008, respectively). There were also fewer
      bacteria on the implanted wires in the groups treated with ceftriaxone (5.47
      log10cfu/cm2) or ceftriaxone/DC (2.82 log10cfu/cm2) than in the untreated
      controls (6.44 log10cfu/cm2 [P = 0.0003 and 0.0002, respectively]). There were
      fewer bacteria in the ceftriaxone/DC rats than in the ceftriaxone-alone- and
      fixed DC-alone-treated rats (P = 0.0017 and 0.0016, respectively). Fixed DC with
      an antibiotic may be useful for treating foreign-body infections caused by S.
      aureus.

PMID- 30293678
TI  - Relevance or performance: potential savings associated with verification of prior
      results before performing microbiology analysis.
AB  - OBJECTIVE: In an era of rising healthcare expenditures, it is critical to find
      ways to decrease cost. The objective of this study is to evaluate the number of
      repeated tests and the associated cost savings in a university-affiliated
      hospital. METHODS: The following 7 microbiology analysis were assessed for
      nonrepeat testing: HCV antibody, HBV core antibody, CMV IgG, rubella IgG,
      Treponema pallidum antibodies, Clostridioides difficile toxin detection, and
      vancomycin-resistant enterococci PCR. Presence of a prior positive result leads
      to the cancellation of subsequent orders. RESULTS: Percentages of not repeated
      test ranged from 0.1% to 21.4%. Rubella IgG had the highest proportion of
      unnecessary repeat testing. Total cost savings were estimated at $33,627 for
      2016. CONCLUSION: Unnecessary repeated microbiologic test can account for a non
      negligible part of total volume test. Use of an automated software to detect
      unnecessary repeated microbiologic test through laboratory information system can
      generate important savings.

PMID- 30293679
TI  - Numerical and analytical investigation of the possibilities to enhance the
      thermal conductivity of core-shell particle packed beds.
AB  - We report on a numerical study of the thermal conductivity of core-shell particle
      packed bed columns. Covering a variety of packing structures and a broad range of
      mobile phase and porous zone conductivities, it was in all cases found that
      switching to particles with a highly conducting core (e.g., with a gold or copper
      core instead of a silica core) would produce a much smaller increase of the
      effective heat conductivity of the bed (keff) than previously expected in
      literature. We found maximal increases on the order of some 20-70%, which is much
      lower than the potential increases up to 2000% assumed in literature. The
      overestimation in literature could be attributed to the fact that this literature
      was based on an incorrect extrapolation of the Zarichnyak-model which was the
      heat conductivity model predominantly used up till now. On the other hand, the
      computed relationships between keff and the core conductivity obtained in the
      present study are in good agreement with an analytical solution derived from the
      effective medium theory, a theory which is physically much more relevant for the
      case at hand than the Zarichnyak-model. The results also show that the observed
      increase in effective bed conductivity between fully porous and core-shell
      particle beds frequently observed in literature is not only due to the presence
      of the core, but that differences in the shell layer conductivity can play an
      equally important role. In addition, it could also be demonstrated that, if ways
      could be found to increase the conductivity of the shell layer, this would
      produce a much stronger increase of the overall bed conductivity than will ever
      be possible by increasing the conductivity of the cores.

PMID- 30293680
TI  - Co3O4 nanoparticles at sublethal concentrations inhibit cell growth by impairing
      mitochondrial function.
AB  - Co3O4 nanoparticles (NPs) are one kind of the important nanomaterials that have
      the application potential in catalyst, electrochromic devices, sensors, etc.
      However, their biological effect remains to be detailed. In this study, we
      investigated the effect of the as-synthesized Co3O4 NPs (15-30 nm) on the growth
      of mammalian cells, and found that the NPs severely inhibited cell growth at the
      sublethal concentrations from 12.5 to 200 mg/L. Interestingly, the NPs did not
      cause obvious cell death and ROS accumulation, indicating that their inhibitory
      effect was not attributed to both apoptosis- or necrosis-related cell death and
      ROS accumulation. Transcription profiling analysis revealed that the NPs caused
      remarkable down regulation of the genes involved in mitochondrial functions.
      Transmission electron microscopy (TEM) and biochemical analysis further showed
      that the NPs might interact with the mitochondria, impairing the mitochondrial
      membrane potential (MMP) and ATP production. This study uncovers a mitochondrial
      respiratory chain-related and ROS-independent toxicity mechanism of Co3O4 NPs in
      eukaryotic cells.

PMID- 30293681
TI  - Crystal structure of an ENT domain from Trypanosoma brucei.
AB  - Trypanosoma brucei (T. brucei) is a parasitic protozoan causing human sleeping
      sickness and related animal diseases. ENT (EMSY N-terminal) domain was first
      found in EMSY protein which has been proved to be involved in multiple biological
      processes such as DNA repair, tumorigenesis, and transcriptional regulation. So
      far, little is known about the function and structure of ENT domains from
      protozoan. Q385P5 from T. brucei, containing an ENT domain at its N-terminus, is
      a conserved protein in related kinetoplastid parasites. In this work, the crystal
      structure of ENT domain of Q385P5 (TbENT) was solved at a resolution of 2.3 A.
      TbENT adopts a club-like shape consisting of five helixes, which is similar to
      the structure of human EMSY ENT domain (HsENT). Interestingly, TbENT shows
      significantly different orientation on the fifth alpha-helix compared with HsENT.
      Meanwhile, human HP1 interacts with a conserved motif adjacent to EMSY ENT
      domain. However, this conserved binding motif is absent in Q385P5. These
      differences may imply the different protein interactions and roles of Q385P5 and
      its ENT domain in T. brucei.

PMID- 30293682
TI  - Three-dimensional model of intracellular and intercellular Ca2+ waves propagation
      in endothelial cells.
AB  - Intracellular and intercellular Ca2+ waves play key roles in cellular functions,
      and focal stimulation triggers Ca2+ wave propagation from stimulation points to
      neighboring cells, involving localized metabolism reactions and specific
      diffusion processes. Among these, inositol 1,4,5-trisphosphate (IP3) is produced
      at membranes and diffuses into the cytoplasm to release Ca2+ from endoplasmic
      reticulum (ER). In this study, we developed a three-dimensional (3D) simulation
      model for intercellular and intracellular Ca2+ waves in endothelial cells (ECs).
      3D model of 2 cells was reconstructed from confocal microscopic images and was
      connected via gap junctions. Cells have membrane and cytoplasm domains, and
      metabolic reactions were divided into each domain. Finally, the intracellular and
      intercellular Ca2+ wave propagations were induced using microscopic stimulation
      and were compared between numerical simulations and experiments. The experiments
      showed that initial sharp increases in intracellular Ca2+ occurred approximately
      0.3 s after application of stimuli. In addition, Ca2+ wave speeds remained
      constant in cells, with intracellular and intercellular speeds of approximately
      35 and 15 MUm/s, respectively. Simulations indicated initial increases in Ca2+
      concentrations at points of stimulation, and these were then propagated across
      stimulated and neighboring cells. In particular, initial rapid increases in
      intracellular Ca2+ were delayed and subsequent intracellular and intercellular
      Ca2+ wave speeds were approximately 25 and 12 MUm/s, respectively. Simulation
      results were in agreement with those from cell culture experiments, indicating
      the utility of our 3D model for investigations of intracellular and intercellular
      messaging in ECs.

PMID- 30293683
TI  - Corrigendum to "A transient post-translational modification of active site
      cysteine alters binding properties of the parkinsonism protein DJ-1" [Biochem.
      Biophys. Res. Commun. 504 (1) (2018 Sep 26) 328-333].

PMID- 30293684
TI  - NFAT5 promotes in vivo development of murine melanoma metastasis.
AB  - Malignant melanoma is one of the most fatal and aggressive skin cancers,
      originating from pigment-containing melanocytes. Despite progress in clinical
      research, treatment options for malignant melanoma have been limited. The nuclear
      factor of activated T-cell 5 (NFAT5), originally identified as tonicity regulated
      transcription factor Ton/EBP, is now known as a carcinogenic gene in several
      types of cancer pathology. In this study, we knocked down NFAT5 to investigate
      its role in melanoma cancer. shRNA-mediated knockdown of NFAT5 led to a
      significant decrease in cell proliferation in vitro. Additionally, depletion of
      NFAT5 inhibited the cell migratory ability of B16BL6 melanoma cells and led to
      more accumulation at the G2/M phase of the cell cycle. Furthermore, NFAT5 was
      essential for the development of melanoma cancer pathophysiology in an in vivo
      mouse model. NFAT5 knockdown-induced tumor growth was slow and tumor volume was
      significantly reduced compared to mock controls. Moreover, NFAT5 knockdown was
      associated with a low number of metastatic nodules on the lung and liver. To our
      knowledge, our data demonstrate for the first time a role of NFAT5 in the
      development of melanoma. We provide evidence for NFAT5 as a marker of cell
      migration and metastasis, indicating that NFAT5 represents a novel therapeutic
      target in melanoma.

PMID- 30293685
TI  - Oral administration of indole substituted dipyrido[2,3-d]pyrimidine derivative
      exhibits anti-tumor activity via inhibiting AKT and ERK1/2 on hepatocellular
      carcinoma.
AB  - Development of an effective and safe anti-cancer drug is an urgent request for
      hepatocellular carcinoma (HCC). In this study, we synthesized a series of novel
      indole substituted dihydropyrido[2,3-d]pyrimidines through the multicomponent
      reactions to connect pyrido[2,3-d]pyrimidine and indole moities via an one-pot
      three-component reaction of 3-cyanoacetyl indoles 1, various aromatic aldehyde 2,
      and 2,6-diaminopyrimidin-4(3H)-one 3. Subsequently, we screened their
      cytotoxicity via CCK-8 assay in HepG2 cells, a human hepatoma cell line and chose
      compound 4p that showed the lowest dosage of IC50 to study the antitumor
      activities to HCC. Interestingly, 4p significantly induced the cell cycle arrest
      and apoptosis of HepG2 via targeting AKT and ERK1/2 signaling pathways in vitro.
      To improve the solubility of compound 4p, we hosted this compound into the
      substituted glucopyranose ring of (2-Hydroxypropyl)-beta-cyclodextrin (HBC), a
      cosolvent approved by FDA with the help of ultrasonication and heating. Finally,
      we showed that oral administration of HBC-hosted 4p effectively inhibited tumor
      growth and prolonged the survival time of tumor-bearing mice in subcutaneously
      xenografted model. These results suggest that multicomponent reactions connecting
      pyrido[2,3-d]pyrimidine and indole moities is a productive and economical method
      for the synthesis of anticancer compound, and oral administration of HBC-hosted
      4p is an effective and safe agents for treatment of HCC, whose clinical
      application potency warrant further studies.

PMID- 30293686
TI  - Intrusive memories of trauma: A target for research bridging cognitive science
      and its clinical application.
AB  - Intrusive memories of a traumatic event can be distressing and disruptive, and
      comprise a core clinical feature of post-traumatic stress disorder (PTSD).
      Intrusive memories involve mental imagery-based impressions that intrude into
      mind involuntarily, and are emotional. Here we consider how recent advances in
      cognitive science have fueled our understanding of the development and possible
      treatment of intrusive memories of trauma. We conducted a systematic literature
      search in PubMed, selecting articles published from 2008 to 2018 that used the
      terms "trauma" AND ("intrusive memories" OR "involuntary memories") in their
      abstract or title. First, we discuss studies that investigated internal (neural,
      hormonal, psychophysiological, and cognitive) processes that contribute to
      intrusive memory development. Second, we discuss studies that targeted these
      processes using behavioural/pharmacological interventions to reduce intrusive
      memories. Third, we consider possible clinical implications of this work and
      highlight some emerging research avenues for treatment and prevention,
      supplemented by new data to examine some unanswered questions. In conclusion, we
      raise the possibility that intrusive memories comprise an alternative, possibly
      more focused, target in translational research endeavours, rather than only
      targeting overall symptoms of disorders such as PTSD. If so, relatively simple
      approaches could help to address the need for easy-to-deliver, widely-scalable
      trauma interventions.

PMID- 30293687
TI  - Retrospective study of the incidence of portal vein thrombosis after splenectomy
      in hematological disorders: Risk factors and clinical presentation.
AB  - OBJECTIVE: Portal vein thrombosis (PVT) has been described as a rare complication
      after splenectomy. PVT associated risk factors after splenectomy in hematological
      disorders are poorly recognized. The aim of this study was to assess the
      prevalence and risk factors of PVT incidence in splenectomized patients. METHODS:
      One hundred twelve splenectomized patients with various hematologic diseases
      between 2008 and 2018 were enrolled in this study. Diagnosis was confirmed by
      Doppler ultrasonography (DUSG) and risk factors for PVT were sought based on the
      comparison of clinical and laboratory features between patients without and with
      PVT. RESULT: PVT was diagnosed in 4 (3.57%) patients in spite of receiving
      antiplatelet therapy. Patients with PVT were beta-thalassemia major (n = 2) and
      beta-thalassemia intermedia (n = 2). beta-thalassemia patients had a 3.5 times
      higher odds for PVT (95% CI: 2.41-5.33). No significant differences between
      patients with and without PVT in terms of age, gender and laboratory features
      were found. CONCLUSION: According to our data, beta-thalassemia, especially
      intermediate form, may be a risk factor for PVT and it can occur in spite of
      receiving antiplatelet therapy. Given that beta-thalassemia patients are at risk,
      early PVT detection may be useful for reduction of fatal PVT complication in
      splenectomized patients.

PMID- 30293688
TI  - Objects build orientation, positioning, and curing influence dimensional accuracy
      and flexural properties of stereolithographically printed resin.
AB  - OBJECTIVE: To evaluate the influence of printing parameters on flexural
      properties and accuracy of SLA-printed standard objects. METHODS: Thirty
      specimens were printed in 0 degrees , 45 degrees  and 90 degrees  orientation.
      Fourth nine more specimens were printed evenly on the build platform. forty more
      specimens were printed and polymerized with three curing unit. Length, height and
      width was measured three times for each specimen and compared to the original
      dimensions. Afterwards all specimens underwent a three-point-bending test to
      assess their flexural properties. One way ANOVA and the Post-Hoc all pairs Tukey
      Kramer HSD test were used for data evaluation. RESULTS: The print orientation
      influences the printing accuracy. The parameters printed along the Z-axis are
      particularly prone to inaccuracies. Specimens with 45 degrees  orientation were
      found to be the most accurate. Object printed on the borders of build platform a
      rather prone to inaccuracies than those in the center. The 90 degrees  specimens
      with layer orientation parallel to the axial load showed the superior flexural
      strength and flexural modulus. The use of different curing unit is unlikely to
      affect the objects printing accuracy and flexural properties. SIGNIFICANCE: The
      anisotropical behavior of printed specimens with regards to build orientation and
      positioning was revealed. The understanding of how the adjustable printing
      parameter influence the printing outcome is important for a precise fabrication
      of surgical guides. Inaccuracies up to 10% along the Z-axis, as revealed in the
      present study,may restrict an accurate implant placement.

PMID- 30293689
TI  - Do collagen cross-linkers improve dentin's bonding receptiveness?
AB  - OBJECTIVES: Dentin biomodification using collagen cross-linkers has been proposed
      as one of the strategies to improve bond durability of adhesives to dentin.
      However, literature is not very consistent regarding their benefit, in particular
      when cross-linkers are applied in clinically realistic application times. This
      study investigated the effect of three cross-linkers on the mini-interfacial
      fracture toughness (mini-iFT) of four adhesives bonded to dentin following either
      etch&rinse (E&R) or self-etch (SE) modes. METHODS: 60 molars were randomly
      divided in accordance with the three variables: cross-linker, adhesive and
      bonding mode (n=5). The cross-linkers glutaraldehyde (5wt%; GA), proanthocyanidin
      (6.5wt%; PA), or UVA-activated riboflavin (0.5wt%; RB), and distilled water
      (control) were applied on dentin for 60s after acid-etching (E&R) or before self
      etching (SE). The 3-step E&R adhesive (3E&Ra) OptiBond FL (Kerr), the 2-step SE
      adhesive (2SEa) Clearfil SE Bond 2 (Kuraray Noritake) and the universal adhesives
      G-Premio Bond (GC) and Prime&Bond Active (Dentsply), the latter two employed in
      both E&R and SE modes, were applied following the respective manufacturer's
      instructions. Composite buildups (8*8*8mm) were made using Filtek Supreme XTE
      (3M) prior to 1-week storage in artificial saliva. After the teeth were sectioned
      into mini-specimens (1.5*2.0*18mm), a single notch was prepared at the adhesive
      dentin interface. Half of the specimens were immediately loaded until failure by
      4-point bending to determine the mini-iFT, while the remaining specimen set was
      tested upon 6-month aging. Data were statistically analyzed with a linear model
      (p<0.05). RESULTS: No significant decrease in mini-iFT was noted only for PA
      (p<0.05), while the mini-iFT decreased for both other cross-linkers and in quite
      a similar way as when solely water (Wa) was applied. SIGNIFICANCE: The cross
      linker proanthocyanidin (PA) applied in clinically relevant conditions was able
      to maintain a stable mini-iFT after 6-month aging. The incorporation of UVA
      activated riboflavin (RB) and glutaraldehyde (GA) in the dentin-bonding protocol
      appeared not effective to improve the stability of adhesive-dentin interfaces.

PMID- 30293690
TI  - The effect of the conductivity of a film located near a piezoelectric resonator
      with a lateral electric field based on the PZT ceramics on its characteristics.
AB  - In this paper, we investigated theoretically and experimentally the effect of the
      conductivity of the film located in the immediate vicinity of the free side of a
      piezoelectric resonator based on the PZT ceramics on its characteristics. It is
      shown that with increasing the conductivity of the film at first the parallel
      resonant frequency does not change, then it decreases in a certain interval and
      after that remains practically constant. With increasing the width of the gap
      between the film and the resonator, the resonant frequency increases and reaches
      the saturation. At that the degree of the total frequency change decreases with
      decreasing the conductivity of the film. We also investigated the dependence of
      the maximum value of the real part of the electrical impedance on the film
      conductivity at the different values of the width of the gap between the film and
      the resonator. The dependences of the maximum value of the real part of the
      electrical impedance on the width of the gap between the film and the resonator
      are also obtained for different values of the film conductivity. A comparison of
      the theoretical and experimental data showed their good qualitative agreement.

PMID- 30293691
TI  - Signal noise based transfer function approach for reliability estimation of
      ultrasonic inspection.
AB  - In recent years several methods for reducing the burden of experimentation for
      obtaining Probability of Detection (PoD) curves have been proposed, especially
      involving the use of numerical simulation. In particular, there is much interest
      in being able to estimate the PoD capabilities of a given NDE method, target
      embodiment and material, provided this is known for some canonical material for
      the same combination of method/embodiment. Ultrasonic experiments on materials
      with low signal to noise ratio (SNR) are often difficult and time consuming since
      the higher signal noise causes serious complications. Set in this context, this
      paper proposes an approach for transferring PoD curves among materials with
      different SNR values. The classical transfer function PoD approach is based on
      the hypothesis that the ratio of signals in related quadrants is equal, which
      requires large datasets for multiple quadrants. The approach proposed here
      directly deals with SNR instead of the ratio of signals, and thus requires only
      the experimental data of the parent application. The new approach is illustrated
      through example cases involving the prediction of PoD curves for ultrasonic
      inspection of an aluminium plate using the empirical PoD data for the same in
      austenitic stainless steel and mild steel. The approach is also demonstrated in
      each of the possible combinations among these three materials.

PMID- 30293692
TI  - Phantom limb sensations in the ear of a patient with a brachial plexus lesion.
AB  - Referred phantom sensations are frequently reported following a peripheral
      injury. However, very few cases describe such sensations of the ear, and it
      remains unclear how the aural nerve territory can be remapped to one specific
      peripheral nerve region. We report on a patient with brachial plexus avulsion who
      underwent sensory testing and was asked to report the location of the stimulated
      site and any other sensations experienced. The patient spontaneously described
      the sensation of his arm being separate from his body. Despite visual input, he
      felt that his fist was closed, with his thumb pointing inward. Importantly, he
      felt clear and reproducible sensations from the affected arm when the ipsilateral
      ear was touched. These referred sensations were noted just 15 days after
      sustaining the injury. The arm nerve territory was systematically remapped to a
      specific aural nerve territory by applying both manual and electrical
      stimulation. Stimulation of the external ear, which is innervated by the vagus
      nerve, showed high spatial specificity for the dorsal and volar skin surfaces of
      the limb, and clearly delineated digits. Somatosensory-evoked potentials
      indicated that cortical adaptation in the somatosensory stream transferred a
      spatially organized map of the limb to the skin of the outer ear. This referral
      of sensations to the ear, as distinct from the face, provides evidence of highly
      specific topographical reorganization of the central nervous system following
      peripheral injury. Rapid map changes in the phantom sensation to the ear as a
      function of stimulation of vagus nerve suggest that the reorganization process
      can occur in cortex rather than in the brainstem.

PMID- 30293693
TI  - Compensatory Cognitive Training for psychosis: Effects on negative symptom
      subdomains.
AB  - Research identifying the effects of cognitive training on negative symptoms of
      psychosis is limited. We examined the effects of Compensatory Cognitive Training
      (CCT) on expressive deficits and social amotivation in a randomized controlled
      trial comparing CCT to standard pharmacotherapy alone in 43 individuals with
      psychosis. ANCOVA analyses demonstrated significant CCT-associated effects on
      both expressive deficits and social amotivation. Moreover, improvements in both
      sub-domains were associated with improvements in global life satisfaction, with
      improvements in social amotivation also related to increased social contact. CCT
      appears to be a beneficial treatment approach for improving multiple aspects of
      negative symptoms.

PMID- 30293695
TI  - Searle on the biology of seeing.
AB  - Searle offers an account of seeing as a conscious state not constituted by the
      object(s) seen. I focus in this article on his biological case for this thesis,
      and argue that the biological considerations he adduces neither establish his own
      position nor defeat a rival object-inclusive view. I show (among other things)
      that taking seeing to be a biological state is compatible with its being
      (partially) constituted by the object(s) seen.

PMID- 30293696
TI  - Metformin Ameliorates Periapical Lesions through Suppression of Hypoxia-induced
      Apoptosis of Osteoblasts.
AB  - INTRODUCTION: Intramuscular injection of metformin has been shown to inhibit the
      progression of periapical lesions in rats by decreasing the number of receptor
      activator of nuclear factor-kappabeta ligand- and tartrate-resistant acid
      phosphatase-positive cells. In this study, we investigated the effect of
      metformin on hypoxia-induced apoptosis of osteoblasts and the therapeutic
      activity of intracanal metformin in induced periapical lesions in rats. METHODS:
      The influence of metformin on hypoxia-induced mitochondrial superoxide production
      in human osteoblasts was examined by using MitoSOX (Invitrogen, Carlsbad, CA)
      fluorescence dye signaling. The release of cytochrome c from mitochondria and the
      cleavage of procaspase-9 and poly(adenosine diphosphate-ribose) polymerase were
      evaluated by Western blot analysis. Apoptotic cell fraction was assessed by DNA
      content flow cytometry. In a rat model of induced periapical lesions, the effect
      of intracanal metformin on disease progression was appraised by 2-dimensional
      radiography and micro-computed tomographic imaging. Oxidative lesions and
      apoptotic activity of osteoblasts in vivo were estimated, respectively, by 8
      hydroxy-2'-deoxyguanosine staining and terminal deoxynucleotidyl transferase dUTP
      nick end labeling. RESULTS: Metformin inhibited hypoxia-enhanced mitochondrial
      superoxide production in osteoblasts. Metformin suppressed hypoxia-induced
      cytochrome c release from mitochondria and the cleavage of procaspase-9 and
      poly(adenosine diphosphate-ribose) polymerase. Metformin repressed hypoxia
      augmented apoptotic cell fraction. In a rat model, intracanal metformin
      diminished the size of periapical lesions and the oxidative damage and apoptotic
      activity in osteoblasts. CONCLUSIONS: Hypoxia increased oxidative stress in
      osteoblasts and enhanced cell death through activation of the mitochondrial
      pathway of apoptosis. Metformin attenuated the oxidative and cytotoxic action of
      hypoxia. The therapeutic effect of metformin on periapical lesions is partially
      caused by its antioxidative activity.

PMID- 30293697
TI  - New developments in liquid-liquid extraction, surface modification and
      agglomerate-free processing of inorganic particles.
AB  - This review describes new methods for the particle extraction through liquid
      liquid interface (PELLI). The discovery of new surface modification techniques,
      advanced extractors and new adsorption mechanisms enabled novel applications of
      PELLI in nanotechnology of metals, quantum dots, oxides and hydroxides. Colloidal
      and interface chemistry of PELLI is emerging as a new area of technological and
      scientific interest. The progress achieved in the understanding of particle
      behavior and interactions at the liquid-liquid interface, phase transfer and
      interface reactions allowed for the development of new extraction mechanisms. An
      important breakthrough was the development of surface modification techniques for
      extraction of functional oxides. Especially important is the possibility of
      particle transfer from the synthesis medium to the device processing medium,
      which facilitates agglomerate-free processing of functional nanoparticles.
      Multifunctional extractor molecules were discovered and used as capping and
      reducing agents for particle synthesis or dispersing and charging agents for
      colloidal processing. The progress achieved in the development of extractors and
      extraction mechanisms has driven the advances in the surface modification and
      functionalization of materials. New PELLI techniques were used for the
      development of advanced materials and devices for optical, photovoltaic, energy
      storage, electronic, biomedical, sensor and other applications.

PMID- 30293698
TI  - Apostle Islands National Lakeshore: A Review of Search and Rescue and Emergency
      Medical Services Operations, 2006-2015.
AB  - INTRODUCTION: Apostle Islands National Lakeshore (APIS) lies at the northern tip
      of Wisconsin and is home to a network of 21 islands along Lake Superior. The goal
      of this report is to investigate search and rescue (SAR) and emergency medical
      services (EMS) trends at APIS in an effort to improve visitor safety and resource
      allocation. METHODS: This study is a retrospective analysis reviewing APIS SAR
      reports and annual EMS summary reports from January 1, 2006, to December 31,
      2015. Information related to incident type, incident date, individual demographic
      characteristics and activities, injury/illness type, cost, and contributing
      factors were recorded and analyzed in frequency tables. RESULTS: From 2006 to
      2015, APIS SAR conducted 133 total missions assisting 261 individuals-200 not
      injured/ill, 57 injured/ill, and 4 fatalities. Median cost per SAR incident
      involving aircraft totaled $21,695 (range: $2,993-141,849), whereas incidents not
      involving aircraft had a median cost of $363 (range: $35-8,830). Nonmotorized
      boating was the most common activity resulting in SAR incidents. All 4 fatalities
      were attributed to drowning while kayaking or swimming. Cold-related
      injury/illness accounted for nearly half of all injuries/illnesses (45%) with the
      most commonly reported contributing factor being high winds. EMS responded to a
      total of 134 incidents. Trauma and first aid accounted for 43% and 34% of EMS
      workload, respectively. CONCLUSIONS: Overall, this study highlights the hazards
      associated with the frigid and rough conditions of Lake Superior. The reported
      results aim to help APIS personnel more saliently convey risks to visitors and
      plan appropriately in an effort to decrease the need for future rescues.

PMID- 30293699
TI  - Emerging immunotherapeutic strategies targeting telomerases in genitourinary
      tumors.
AB  - Telomerase activity and telomere length are essential for the pathogenesis of
      several human diseases, including genitourinary tumors. Telomerase constitutes a
      complex system that includes human telomerase reverse transcriptase (hTERT),
      human telomerase RNA component (hTR) and telomerase associated protein 1 (TEP1),
      which are overexpressed in tumor cells compared to normal cells and are involved
      in the carcinogenesis and progression of renal cell carcinoma (RCC), bladder (BC)
      and prostate cancer (PCa). In addition, telomerase degraded peptide fragments
      expressed on the surface of tumor cells lead to their recognition by immune
      cells. On this scenario, in vitro and in vivo studies have shown effective anti
      tumor activity of hTERT-tailored strategies in genitourinary tumors, including
      active immunotherapy with hTERT-peptide vaccines and passive immunotherapy with
      hTERT-transduced T cell infusion. This review emphasizes the role of telomerase
      in the carcinogenesis and progression of genitourinary tumors, thus underlying
      the potential of emerging telomerase-tailored immunotherapies in these patients.

PMID- 30293700
TI  - Chondrosarcoma: An overview of clinical behavior, molecular mechanisms mediated
      drug resistance and potential therapeutic targets.
AB  - Sarcomas are known as a heterogeneous class of cancers arisen in the connective
      tissues and demonstrated various histological subtypes including both soft tissue
      and bone origin. Chondrosarcoma is one of the main types of bone sarcoma that
      shows a considerable deficiency in response to chemotherapy and radiotherapy.
      While conventional treatment based on surgery, chemo-and radiotherapy are used in
      this tumor, high rate of death especially among children and adolescents are
      reported. Due to high resistance to current conventional therapies in
      chondrosarcoma, there is an urgent requirement to recognize factors causing
      resistance and discover new strategies for optimal treatment. In the past decade,
      dysregulation of genes associated with tumor development and therapy resistance
      has been studied to find potential therapeutic targets to overcome resistance. In
      this review, clinical aspects of chondrosarcoma are summarized. Moreover, it
      gives a summary of gene dysregulation, mutation, histone modifications and non
      coding RNAs associated with tumor development and therapeutic response
      modulation. Finally, the probable role of tumor microenvironment in
      chondrosarcoma drug resistance and targeted therapies as a promising molecular
      therapeutic approach are summarized.

PMID- 30293701
TI  - Can we avoid the toxicity of chemotherapy in elderly cancer patients?
AB  - Although approximately 50% of cancer patients are 70 years of age or older,
      cancer treatment in the elderly remains a therapeutic challenge. The elderly form
      a very heterogeneous group in relation to their general health state, degree of
      dependence, comorbidities, performance status, physical reserve and geriatric
      situation, for which therapeutic decisions must be made in an individualized
      manner. In addition, changes in pharmacokinetics and pharmacodynamics of the
      drugs occur with age, as well as the tolerance of the tissues, leading to a
      narrowing of the therapeutic margin and an increase in toxicity. In the general
      population, Performace Status (PS) has traditionally been used to estimate
      tolerance to chemotherapy, but in the elderly population it is not useful. In
      this review we summarize the current knowledge about the pharmacology of
      antineoplastic drugs in the elderly and the tools available to help us identify
      risk of chemotherapy toxicity in these patients.

PMID- 30293702
TI  - Stereotactic body radiation therapy (SBRT) on renal cell carcinoma, an overview
      of technical aspects, biological rationale and current literature.
AB  - BACKGROUND: Stereotactic body radiotherapy (SBRT) is characterized by the
      delivery of high doses of ionizing radiation in few fractions. It is highly
      effective in achieving local control, and, due to the high biological effective
      dose administered, it seems to overcome the radioresistance of renal cell
      carcinoma (RCC). Thus, SBRT could constitute a treatment option for the
      management of localized RCC in patients who are not surgical candidates. In this
      paper, we report an overview about data from the current evidence about SBRT in
      patients affected by localized RCC. MATERIALS AND METHODS: A non-systematic
      review was performed, including data from both retrospective and prospective
      studies focusing on the use of SBRT for localized RCC and its biological
      rationale. Furthermore, ongoing trials on this issue are reported. CONCLUSION:
      Currently, SBRT might be considered a treatment alternative in inoperable
      patients affected by primary RCC. Currently, dose-escalation to 48 Gy in 3-4
      fractions are effective and well tolerated. Emerging role of immune therapies in
      RCC patients warrant further studies to explore interactions between SBRT and
      immune response.

PMID- 30293703
TI  - Criteria for eligibility to cisplatin in the curative treatment of head and neck
      cancer: Consensus opinion from a panel of experts.
AB  - Squamous-cell carcinoma of the head and neck (SCCHN) is an important problem in
      Brazil, where epidemiological and socioeconomic features often create barriers to
      the implementation of combined modalities with curative potential. Cisplatin
      improves the efficacy of radiotherapy in the adjuvant treatment of localized
      SCCHN and in the definitive therapy of locally advanced disease. However, the
      addition of high-dose cisplatin to radiotherapy increases treatment toxicity and
      is not always warranted. A panel of experts convened in Sao Paulo, Brazil, for
      discussions and recommendations regarding the use of high-dose cisplatin in
      combination with radiotherapy in SCCHN. In addition to discussing their
      professional experience, panel members used the current literature to provide
      evidence-based, practical recommendations regarding sociodemographic or medical
      criteria that may preclude safe administration of cisplatin. It is hoped that the
      application of these recommendations in clinical practice may improve therapeutic
      results in Brazil and other countries with similar health-care environments.

PMID- 30293704
TI  - Revisiting the dynamic cancer stem cell model: Importance of tumour edges.
AB  - The lack of an effective treatment against cancer is not only due to its huge
      heterogeneity, but also to the fact that we don't have an answer to the question
      on how cancer originates. Among the proposed models to explain the development of
      cancer, the hierarchical model has been widely accepted. Nevertheless, this model
      fails to explain several experimental observations such as the cancer stem cells
      (CSCs) location inside a tumour or the differences between primary and metastatic
      tumours. Moreover, increasing evidence shows that the CSC phenotype is not a
      rigid state. Here, we present a critical review on the assumed tumour development
      models emphasizing the relevance of the dynamic and changing nature of cancer and
      the CSCs population in which the tumour microenvironment plays a crucial role and
      we propose a new model of tumour origin that could have an impact on new
      therapeutic strategies.

PMID- 30293705
TI  - The role of PDGF-B/PDGFR-BETA axis in the normal development and carcinogenesis
      of the breast.
AB  - PDGFs/PDGFRs axis is documented as an important tumor-promoting agent and
      potential therapeutic target for several human carcinomas, including breast
      cancer. However, little is known about the role played by the PDGF family members
      in the normal development of the breast tissue, breast carcinogenesis and tumor
      microenvironment dynamics Despite its potent pro-lymphangiogenic effects, PDGF
      B/PDGFR-beta axis remains controversial and incompletely elucidated in the field
      of breast cancer, with emphasis to its differential implications in breast cancer
      molecular subtypes. Although some data are available concerning this aspect,
      little or no information is found regarding the role of the PDGF-B/PDGFR-beta
      axis in rare and aggressive types of breast cancers, such as triple negative
      breast cancers (TNBCs) and its associated subtypes This review attempted to
      gather as many data as possible concerning PDGFs family members in the normal
      breast tissue and in breast carcinogenesis with special focus on their role in
      diagnosis and therapeutic approach.

PMID- 30293706
TI  - Duration of first-line treatment for metastatic colorectal cancer: Translating
      the available evidence into general recommendations for routine practice.
AB  - Over the last two decades the number of front-line regimens for metastatic
      colorectal cancer has progressively increased. Nevertheless, there is still no
      consensus on the optimal duration of treatment or the role of de
      escalated/maintenance strategies after induction chemotherapy. In this article we
      provide an overview of the studies that addressed the duration of first-line
      systemic treatment with cytotoxic agents plus or minus targeted therapies
      highlighting caveats and limitations of the same. Also, we try to translate the
      available evidence into practical recommendations that can be used in everyday
      practice to inform treatment decisions. The main conclusion of our review article
      is that continuing induction treatment until progression may improve disease
      control but there is no evidence to suggest that adopting this practice can
      prolong survival. On the other hand, de-escalated treatment strategies offer an
      opportunity to reduce the burden of toxicity while maintaining satisfactory
      oncological outcomes.

PMID- 30293707
TI  - Critical appraisal of oncological safety of stent as bridge to surgery in left
      sided obstructing colon cancer; a systematic review and meta-analysis.
AB  - This meta-analysis aims to determine the long-term oncological outcomes of SEMS
      as bridge to surgery (BTS) versus emergency surgery (ES). A systematic search
      without restrictions was conducted, and all studies comparing SEMS with ES
      reporting on long-term outcomes were included. Methodological quality was
      assessed using the appropriate tools. Twenty-one comparative studies were
      selected, reporting on 1919 patients. Meta-analysis showed no significant
      difference regarding three- and five-year overall survival (OR = 0.85 (0.68-1.08)
      and OR = 1.04 (0.68-1.57), respectively), disease-free survival (OR = 0.96 (0.73
      1.26) and OR = 0.86 (0.54-1.36), respectively) and local recurrence rate (OR =
      1.32 (0.78-2.23)). Permanent stomas were significantly lower in the SEMS group
      (OR 0.49 (0.32-0.74)). Sensitivity analysis on three-year survival showed
      opposite outcomes, with a trend towards worse survival in the SEMS group when
      only RCTs are taken into account. In conclusion, when in experienced hands, SEMS
      placement as BTS seems oncologically safe.

PMID- 30293708
TI  - C-MET as a potential target therapy toward personalized therapy in some pediatric
      tumors: An overview.
AB  - Althoughpediatric tumors represent less than 1% of all new cancer diagnoses, they
      still rank the second in the list of disease-related morbidity and mortality in
      children in the US. Combining biomarker-driven targeted therapy with
      individualized genomic analysis is the principle of precision medicine trials.
      The cellular-mesenchymal-epithelial transition (c-MET) factor receptor signaling
      pathway plays an important role in many physiological functions including
      embryological development. It, tightly, regulates changes in cell growth and
      survival, it also defines the general pattern of invasive growth during normal
      development. Aberrant MET signaling is the fundamental cause of carcinogenesis of
      many pediatric tumors and it may play a role in tumor metastasis that leads to
      the poor prognosis in most cancer patients. This review describes c
      MET/hepatocyte growth factor (HGF) signaling pathway relevance to pediatric
      tumors. Also, it discusses the pre-clinical and clinical studies for inhibitors
      of this pathway.

PMID- 30293709
TI  - The effects of mitochondria-associated long noncoding RNAs in cancer
      mitochondria: New players in an old arena.
AB  - LncRNAs, as new players in the old battle against cancer, are significant
      components of gene regulatory networks. Mitochondria-associated lncRNAs have
      newly been discovered to work in concert with transcription factors and
      epigenetic regulators to modulate mitochondrial gene expression and mitochondrial
      function. Many mitochondria-associated lncRNAs regulate mitochondrial
      biosynthesis, bioenergetics, apoptosis and possibly govern the cross-talk of
      mitochondria with nuclei. The complexity of mitochondria-associated lncRNAs is
      now just starting to envisage. In this review, we collected available evidence
      that reinforces the importance of mitochondria-associated lncRNA in cancer
      metabolism, apoptosis, and cell senescence. For the non-exhaustive list of
      mitochondria-associated lncRNAs, we identified 18 lncRNAs in total (mitochondria
      encoded lncRNAs or nuclei encoded mitochondria function associated lncRNAs) as
      emerging new players in cancer mitochondrial function. As lncRNAs exhibit cancer
      type-specific expression patterns, they are attractive targets for selective
      therapeutic interventions. Manipulation of their function may thus represent a
      valuable strategy for future cancer treatment.

PMID- 30293710
TI  - The Era of PARP inhibitors in ovarian cancer: "Class Action" or not? A systematic
      review and meta-analysis.
AB  - INTRODUCTION: Carboplatin is the milestone of epithelial ovarian cancer (EOC)
      treatment, thus response to platinum is the major prognostic factor. Among
      platinum-sensitive patients, 40% carry a germline or somatic BRCA1/2 mutation. In
      this scenario a new class of drugs, the PARP inhibitors (PARPis), produced a
      significant improvement in long-term disease control. In order to make an
      aggregate evaluation of the impact of these agents, we performed a systematic
      review and meta-analysis. PATIENTS AND METHODS: Clinical trials were selected by
      searching "Pubmed" database and abstracts from major cancer meetings. We
      considered the January 2008 - April 2018 time frame. Progression free survival
      (PFS) was the primary end-point, toxicities were secondary end-points. Hazard
      ratios (HRs) of PFS, with confidence intervals, and risk ratios of grade 3-4
      toxicity rates, were extracted from retrieved studies and included in the current
      analysis. Meta-analysis was carried out by the fixed and random effect models. We
      conducted this meta-analysis to also compare indirectly the efficacy of different
      PARPis in EOC patients. RESULTS: Five randomized trials for a total of 1839
      patients were selected and included in the final analysis. In particular, we
      evaluated a BRCA-mutant cohort (871 patients) with a pooled HR 0.25 (95%CI 0.21
      0.31) and the BRCA-wild type cohort (836 patients) with a pooled HR 0.41 (95%CI
      0.31-0.55), respectively. Regarding safety profile, no significant differences
      were detected in all grade toxicities, however, taking into account 3-4 grade
      toxicities and SAEs (severe adverse events), we show that rucaparib-treated
      patients reported major abdominal pain events, while niraparib-treated patients
      were associated with the highest percentage of haematological toxicities,
      hypothesizing a drug effect for the safety analysis. In the indirect comparisons,
      significant differences were not detected on PFS for the different agents.
      CONCLUSIONS: We confirm a significant benefit in survival outcome of PARPis for
      EOC patients with a "class effect" on the bases of narrow CI and indirect
      comparisons in the different groups. Therefore, we underline that this strategy
      is of special value in BRCA-mutated patients because genetic testing allows best
      patient selection for all PARPis with the added value of individualized
      prevention in familiars.

PMID- 30293711
TI  - Supporting Supportive Care in Cancer: The ethical importance of promoting a
      holistic conception of quality of life.
AB  - Advances in anticancer therapies and increasing attention towards patient quality
      of life make Supportive Care in Cancer (SCC) a key aspect of excellence in
      oncological care. SCC promotes a holistic conception of quality of life
      encompassing clinical, ethical/existential, and spiritual dimensions. Despite the
      calls of international oncology societies empirical evidence shows that SCC has
      not yet been implemented. More efforts are needed given the clinical and ethical
      value of SCC not only for patients, but also for clinicians and hospitals.
      Drawing on different literature sources, we identify and discuss three important
      barriers to the implementation of SCC: 1) organisational - lack of adequate
      resources and infrastructures in over-stretched clinical environments, 2)
      professional- burnout of cancer clinicians; and 3) cultural - stigma towards
      death and dying. We add an ethical counselling framework to the SCC
      implementation toolkit- which, could offer a flexible and resource-light way of
      embedding SCC, addressing these barriers.

PMID- 30293712
TI  - Radiotherapy in triple-negative breast cancer: Current situation and upcoming
      strategies.
AB  - Triple-negative breast cancer (TNBC) (estrogen receptor-negative, progesterone
      receptor-negative, and HER2-negative) is viewed as an aggressive subgroup of
      breast cancer. Treating patients with TNBC remains clinically challenging. It's
      now well established than radiation therapy is able to improve locoregional
      control in breast cancer patients both after breast conserving surgery or
      mastectomy, with positive impact in high-risk patients for long-term survival.
      Biologic characterization of breast tumor different subtypes, in particular the
      heterogeneous subtype of TNBC could permit to adapt the treatment plan. In the
      present review, summarizing the molecular types, we describe clinical features
      and postoperative radiotherapy current situation for TNBC, and we provide new
      strategies and directions through an adapted radiation therapy.

PMID- 30293713
TI  - Treatment of gynaecological cancer related lower limb lymphoedema with
      liposuction.
AB  - OBJECTIVE: To evaluate outcomes in patients with gynaecological cancer related
      lymphoedema treated with liposuction. METHODS: A prospective analysis of 21
      patients who underwent liposuction followed by compression therapy for chronic
      unilateral lower limb lymphoedema with up to 8 years follow up was performed.
      RESULTS: Duration of lymphoedema prior to liposuction ranged from 4 to 28 years
      (mean 15.2 years). The mean age at time of liposuction was 52 years (range 37
      67). Estimated volume excess in the affected limb ranged from 1.6 to 12 l (mean
      4.7 l). The mean percentage reduction was 92.6% at 6 months (range 59.4-159.9)
      and 88.9% (range 60.9-127.5) at 1 year. Longer term follow-up of 6 patients at 5
      years post-liposuction revealed a mean percentage reduction of 113.6% (range 83.5
      155.5). CONCLUSION: Our experience of liposuction combined with compression
      garments has demonstrated significant and sustainable reduction in limb volume in
      patients with lower limb lymphoedema secondary to gynaecological malignancy.

PMID- 30293714
TI  - Influence of dietary protein intake on body composition in chronic kidney disease
      patients in stages 3-5: A cross-sectional study.
AB  - INTRODUCTION: A controlled protein intake has shown beneficial effects to
      preserve renal function and nutritional status in chronic kidney disease (CKD)
      patients. This study aimed to analyze usual dietary protein intake and its
      potential contribution to body composition in CKD patients in stages 3-5. METHOD:
      Cross-sectional study in 134 CKD patients in stages 3-5 (mean e-GFR: 19.4+/
      8.7ml/min/1.73m2; males 68.7% and primary CKD etiology was diabetes mellitus,
      35.8%). Demographic, clinical and nutritional parameters were evaluated.
      Normalized protein nitrogen appearance (nPNA), was used as a surrogate marker of
      dietary protein intake. The sample was classified into three nPNA groups (Gn):
      G1: <0.8g/kg/day; G2: 0.8-1g/kg/day and, G3: >=1g/kg/day. Assessment of
      nutritional status using the malnutrition-inflammation score (MIS),
      anthropometric measures and laboratory parameters. Analysis of body composition
      and hydration status by bioelectrical impedance analysis (BIVA-101-RJL system).
      Statistical analysis by SPSS v.20. RESULTS: Overall mean nPNA values were 0.91+/
      0.23g of protein/kg BW/day and only 32.1% had a dietary protein intake <0.8g of
      protein/kg BW/day. Most of the CKD patients (65.5%) were in stages 4 or 5.
      Prevalence of protein-energy-wasting (PEW) syndrome measured by MIS was 15%. By
      analyzing differences between nPNA groups, body weight (BW), BMI and triceps
      skinfold (TSF) thickness were significantly higher in the group with nPNA >=1g/kg
      BW/day (G3), whereas a significant inverse relationship was found with the
      percentages of body cell mass (BCM%), fat-free mass (FFM%), muscle mass (MM%) and
      phase angle (PA) in the group with the lowest nPNA (G1). Analysis of gender among
      subjects showed significant differences with BW, FFM%, TSF and mid-arm muscle
      circumference (MAMC%). Linear regression analysis showed that resistance, BCM%,
      MM%, and serum albumin were significant predictors of nPNA as a surrogate marker
      of daily protein intake (R=0.51; R2=0.29; R2 adjusted=0.23; p<0.001). CONCLUSION:
      Controlled protein intake is one of the cornerstones of treatment in CKD
      patients. A low protein intake in patients with CKD stages 3 and 4-5 was
      associated with loss of muscle mass in the advanced-CKD unit. The loss of muscle
      mass appears as an early indicator of nutritional comprised. Factors such,
      elderly age and loss of eGFR, showed lower protein intake and were associated
      with muscle loss, especially in women. Further longitudinal studies are required
      to evaluate the contribution of different protein intakes to uremic symptoms,
      nutritional status, body composition and CKD progression.

PMID- 30293715
TI  - Warburg Effect Metabolism Drives Neoplasia in a Drosophila Genetic Model of
      Epithelial Cancer.
AB  - Cancers develop in a complex mutational landscape. Genetic models of tumor
      formation have been used to explore how combinations of mutations cooperate to
      promote tumor formation in vivo. Here, we identify lactate dehydrogenase (LDH), a
      key enzyme in Warburg effect metabolism, as a cooperating factor that is both
      necessary and sufficient for epidermal growth factor receptor (EGFR)-driven
      epithelial neoplasia and metastasis in a Drosophila model. LDH is upregulated
      during the transition from hyperplasia to neoplasia, and neoplasia is prevented
      by LDH depletion. Elevated LDH is sufficient to drive this transition. Notably,
      genetic alterations that increase glucose flux, or a high-sugar diet, are also
      sufficient to promote EGFR-driven neoplasia, and this depends on LDH activity. We
      provide evidence that increased LDHA expression promotes a transformed phenotype
      in a human primary breast cell culture model. Furthermore, analysis of publically
      available cancer data showed evidence of synergy between elevated EGFR and LDHA
      activity linked to poor clinical outcome in a number of human cancers. Altered
      metabolism has generally been assumed to be an enabling feature that accelerates
      cancer cell proliferation. Our findings provide evidence that sugar metabolism
      may have a more profound role in driving neoplasia than previously appreciated.

PMID- 30293716
TI  - Intraflagellar Transport Complex A Genes Differentially Regulate Cilium Formation
      and Transition Zone Gating.
AB  - Cilia are found on most eukaryotic cell types, serving motility, environment
      sensing, and signaling (cell-cell) functions, and defects cause genetic diseases
      (ciliopathies), affecting the development of many tissues [1]. Cilia are built by
      intraflagellar transport (IFT), a bidirectional microtubule-based motility driven
      by kinesin-2 anterograde (toward ciliary tip) and IFT-dynein retrograde (toward
      ciliary base) motors together with IFT-A and IFT-B cargo adaptor complexes that
      control retrograde and anterograde IFT, respectively [2]. Ciliary composition is
      also facilitated by the transition zone (TZ) at the ciliary base and the
      associated Meckel-Gruber syndrome (MKS) and nephronophthisis (NPHP) modules that
      establish protein diffusion barriers and regulate cilium structure [3]. Although
      the molecular architecture of the IFT machine is emerging [2], how individual
      components contribute to cilium subtype formation and IFT remains relatively
      unexplored, especially in vivo. In addition, little is known about functional
      interactions between IFT and TZ modules. Here, in Caenorhabditis elegans
      (roundworms), we identify cell-type-specific mechanisms by which IFT-A sculpts
      the structures of discrete ciliary subtypes and regulates IFT. We also uncover
      differential roles for IFT-A subunits in controlling the TZ restriction of MKS
      module components and ciliary exclusion (gating) of periciliary membrane
      proteins, with IFT-140 controlling their ciliary entry and IFT-43/121/139
      controlling their ciliary removal. Furthermore, we determine that IFT-A and MKS
      module components synergistically interact to determine cilium structure.
      Overall, this work provides insight into the functional architecture of a
      metazoan IFT-A complex in different cell types and uncovers new relationships
      between ciliopathy-associated IFT-A and TZ modules.

PMID- 30293717
TI  - Distinct Predatory Behaviors in Scimitar- and Dirk-Toothed Sabertooth Cats.
AB  - Over the Cenozoic, large cat-like forms have convergently evolved into
      specialized killers of "megaherbivores" that relied on their large, and laterally
      compressed (saber-like) canines to rapidly subdue their prey [1-5]. Scimitar- and
      dirk-toothed sabertooths are distinct ecomorphs that differ in canine tooth
      length, degree of serration, and postcranial features indicative of dissimilar
      predatory behavior [6-13]. Despite these differences, it is assumed that they
      used a similar "canine-shear" bite to kill their prey [14, 15]. We investigated
      the killing behavior of the scimitar-toothed Homotherium serum and the dirk
      toothed Smilodon fatalis using a comparative sample of living carnivores and a
      new quantitative approach to the analysis of skull function. For the first time,
      we quantified differences in the relative amount and distribution of cortical and
      trabecular bone in coronal sections of skulls to assess relative skull stiffness
      and flexibility [16-19]. We also use finite element analysis to simulate various
      killing scenarios that load skulls in ways that likely favor distinct proportions
      of cortical versus trabecular bone across the skull. Our data reveal that S.
      fatalis had an extremely thick skull and relatively little trabecular bone,
      consistent with a large investment in cranial strength for a stabbing canine
      shear bite. However, H. serum had more trabecular bone and most likely deployed
      an unusual predatory behavior more similar to the clamp-and-hold technique of the
      lion than S. fatalis. These data broaden the killing repertoire of sabertooths
      and highlight the degree of ecological specialization among members of the large
      carnivore guild during the Late Pleistocene of North America.

PMID- 30293718
TI  - Modularity and Overcompensatory Growth in Ediacaran Rangeomorphs Demonstrate
      Early Adaptations for Coping with Environmental Pressures.
AB  - The first known diverse, complex, macroscopic benthic marine ecosystems (late
      Ediacaran, ca. 571-541 Ma) were dominated by the Rangeomorpha, an enigmatic group
      of extinct frondose eukaryotes that are candidate early metazoans [1, 2]. The
      group is characterized by a self-similar branching architecture that was most
      likely optimized for exchange, but nearly every other aspect of their biology is
      contentious [2-4]. We report locally enhanced, aberrant growth ("eccentric
      branching") in a stalked, multifoliate rangeomorph-Hylaecullulus fordi n. gen.,
      n. sp.-from Charnwood Forest (UK), confirming the presence of true biological
      modularity within the group. Random branches achieve unusually large proportions
      and mimic the architecture of their parent branch, rather than that of their
      neighbors (the norm). Their locations indicate exceptional growth at existing
      loci, rather than insertion at new sites. Analogous overcompensatory branching in
      extant modular organisms requires the capacity to orchestrate growth at specific
      sites and occurs most frequently in response to damage or environmental stress,
      allowing regeneration toward optimum morphology (e.g., [5-7]). Its presence in
      rangeomorphs indicates a hitherto unappreciated level of control to their growth
      plan, a previously unrecognized form of morphological plasticity within the
      group, and an ability to actively respond to external physical stimuli. The trait
      would have afforded rangeomorphs resilience to fouling and abrasion, partially
      accounting for their wide environmental tolerance, and may have pre-adapted them
      to withstand predation, weakening this argument for their extinction. Our
      findings highlight that multiple, phylogenetically disparate clades first
      achieved large size through modularity.

PMID- 30293719
TI  - Prevalence of Mutation-Prone Microhomology-Mediated End Joining in a Chordate
      Lacking the c-NHEJ DNA Repair Pathway.
AB  - Classical non-homologous end joining (c-NHEJ), a fundamental pathway that repairs
      double-strand breaks in DNA, is almost universal in eukaryotes and involves
      multiple proteins highly conserved from yeast to human [1]. The genes encoding
      these proteins were not detected in the genome of Oikopleura dioica, a new model
      system of tunicate larvaceans known for its very compact and highly rearranged
      genome [2-4]. After showing their absence in the genomes of six other larvacean
      species, the present study examined how O. dioica oocytes and embryos repair
      double-strand DNA breaks (DSBs), using two approaches: the injection of
      linearized plasmids, which resulted in their rapid end joining, and a newly
      established CRISPR Cas9 technique. In both cases, end joining merged short
      microhomologous sequences surrounding the break (mainly 4 bp long), thus inducing
      deletions larger than for the tunicate ascidian Ciona intestinalis and human
      cells. A relatively high frequency of nucleotide insertions was also observed.
      Finally, a survey of genomic indels supports the involvement of microhomology
      mediated repair in natural conditions. Overall, O. dioica repairs DSBs as other
      organisms do when their c-NHEJ pathway is experimentally rendered deficient,
      using another mode of end joining with the same effect as alternative NHEJ (a
      NHEJ) or microhomology-mediated end joining (MMEJ) [5-7]. We discuss how the
      exceptional loss of c-NHEJ and its replacement by a more mutation-prone mechanism
      may have contributed to reshaping this genome and even been advantageous under
      pressure for genome compaction.

PMID- 30293720
TI  - Wild Birds Learn Songs from Experimental Vocal Tutors.
AB  - In eight groups of animals, including humans and songbirds, juveniles are
      understood to learn vocalizations by listening to adults [1-4]. Experimental
      studies of laboratory-reared animals support this hypothesis for vocal learning
      [5-7], yet we lack experimental evidence of vocal learning in wild animals. We
      developed an innovative playback technology involving automated loudspeakers that
      broadcast songs with distinctive acoustic signatures. We used this technology to
      simulate vocal tutors in the wild and conducted year-long tutoring sessions to
      five cohorts of free-living migratory Savannah Sparrows in eastern Canada. We
      confirm that wild birds learn songs by listening to adult conspecific animals,
      and we show that they pass these songs on to subsequent generations. Further, we
      provide the first experimental evidence in the wild that the timing of exposure
      to tutor song influences vocal learning: wild Savannah Sparrows preferentially
      learn songs heard during both their natal summer and at the outset of their first
      breeding season. This research provides direct experimental evidence of song
      learning by wild animals and shows that wild birds learn songs during two
      critical stages of development early in life. VIDEO ABSTRACT.

PMID- 30293722
TI  - A Human Polymorphism in CHRNA5 Is Linked to Relapse to Nicotine Seeking in
      Transgenic Rats.
AB  - Tobacco addiction is a chronic and relapsing disorder with an important genetic
      component that represents a major public health issue. Meta-analysis of large
      scale human genome-wide association studies (GWASs) identified a frequent non
      synonymous SNP in the gene coding for the alpha5 subunit of nicotinic
      acetylcholine receptors (alpha5SNP), which significantly increases the risk for
      tobacco dependence and delays smoking cessation. To dissect the neuronal
      mechanisms underlying the vulnerability to nicotine addiction in carriers of the
      alpha5SNP, we created rats expressing this polymorphism using zinc finger
      nuclease technology and evaluated their behavior under the intravenous nicotine
      self-administration paradigm. The electrophysiological responses of their neurons
      to nicotine were also evaluated. alpha5SNP rats self-administered more nicotine
      at high doses and exhibited higher nicotine-induced reinstatement of nicotine
      seeking than wild-type rats. Higher reinstatement was associated with altered
      neuronal activity in several discrete areas that are interconnected, including in
      the interpeduncular nucleus (IPN), a GABAergic structure that strongly expresses
      alpha5-containing nicotinic receptors. The altered reactivity of IPN neurons of
      alpha5SNP rats to nicotine was confirmed electrophysiologically. In conclusion,
      the alpha5SNP polymorphism is a major risk factor for nicotine intake at high
      doses and for relapse to nicotine seeking in rats, a dual effect that reflects
      the human condition. Our results also suggest an important role for the IPN in
      the higher relapse to nicotine seeking observed in alpha5SNP rats.

PMID- 30293721
TI  - Shugoshin Is Essential for Meiotic Prophase Checkpoints in C. elegans.
AB  - The conserved factor Shugoshin is dispensable in C. elegans for the two-step loss
      of sister chromatid cohesion that directs the proper segregation of meiotic
      chromosomes. We show that the C. elegans ortholog of Shugoshin, SGO-1, is
      required for checkpoint activity in meiotic prophase. This role in checkpoint
      function is similar to that of conserved proteins that structure meiotic
      chromosome axes. Indeed, null sgo-1 mutants exhibit additional phenotypes similar
      to that of a partial loss-of-function allele of the axis component, HTP-3:
      premature synaptonemal complex disassembly, the activation of alternate DNA
      repair pathways, and an inability to recruit a conserved effector of the DNA
      damage pathway, HUS-1. SGO-1 localizes to pre-meiotic nuclei when HTP-3 is
      present but not yet loaded onto chromosome axes and genetically interacts with a
      central component of the cohesin complex, SMC-3, suggesting that it contributes
      to meiotic chromosome metabolism early in meiosis by regulating cohesin. We
      propose that SGO-1 acts during pre-meiotic replication to ensure fully functional
      meiotic chromosome architecture, rendering these chromosomes competent for
      checkpoint activity and normal progression of meiotic recombination. Given that
      most research on Shugoshin has focused on its regulation of sister chromatid
      cohesion during chromosome segregation, this novel role may be conserved but
      previously uncharacterized in other organisms. Further, our findings expand the
      repertoire of Shugoshin's functions beyond coordinating regulatory activities at
      the centromere.

PMID- 30293723
TI  - Spillovers from the Patient Protection and Affordable Care Act to employer
      sponsored dental insurance enrollment.
AB  - BACKGROUND: Previous study results have indicated that the Patient Protection and
      Affordable Care Act (ACA) health insurance expansion for dependents (called the
      dependent coverage expansion) also led to a dental insurance expansion for
      dependents. In this study, the author examines whether this expansion is due to
      changes in employer-sponsored dental insurance. METHODS: The author compared
      enrollment and oral health care use between 2 groups of young adults in employer
      sponsored dental plans managed by Delta Dental of Michigan before and after the
      initial implementation of the ACA: adults aged 20 through 24 years (eligible for
      the expansion) and adults aged 30 through 34 years (ineligible). RESULTS: The ACA
      dependent coverage expansion led to an increase in both dental plan enrollment
      rates (5.38%; P < .01) and oral health care use rates (3.57%; P < .1) among
      adults aged 20 through 24 years relative to adults aged 30 through 34 years.
      CONCLUSIONS: Although the ACA's dependent coverage expansion led to an increase
      in dental plan enrollment and oral health care use in Michigan, the effects seen
      by other insurers and states are yet to be determined, although the direction
      likely is similar. PRACTICAL IMPLICATIONS: This study's results suggest that
      employers responded to the ACA dependent coverage expansion by expanding
      dependent oral health care coverage.

PMID- 30293724
TI  - APOE E4, rs405509, and rs440446 promoter and intron-1 polymorphisms and dementia
      risk in a cohort of elderly Finns-Helsinki Birth Cohort Study.
AB  - We tested if the epsilon4 major isoform of the APOE gene and rs405509 and
      rs440446 promoter and intron-1 polymorphisms predicted risk of any dementia or
      Alzheimer's disease with diagnoses derived from the Hospital Discharge and Causes
      of Death Registers in 1453 participants of the Helsinki Birth Cohort Study. We
      used Cox proportional hazard models adjusted for sex, year of birth, maximum
      lifetime occupational status and education, and diagnoses of stroke, coronary
      heart disease, mood disorders, and depressive symptoms. APOE epsilon4 predicted
      higher risk of any dementia (hazard ratios >3.68; 95% confidence interval [CI]
      1.76, 7.70) across all statistical models, and when adjusted for rs405509 and
      rs440446. The number of minor alleles in rs405509 or rs440446 was not associated
      with dementia risk (hazard ratios<1.43; 95% CI 0.87, 2.36). As rs405509 or
      rs440446 has been associated with nonpathological cognitive aging in this and
      other cohorts independent of the APOE major isoforms, these findings lend
      credence that APOE locus may be linked with dementia risk and nonpathological
      cognitive aging via separate mechanisms.

PMID- 30293725
TI  - Relationship between variants of 17 newly loci and Parkinson's disease in a
      Chinese population.
AB  - Genetic factors play significant roles in the causes of Parkinson's disease (PD).
      Recently, a meta-analysis of genome-wide association study (GWAS) has identified
      17 loci associated with PD. The objective of our study was to investigate the
      association of 17 single-nucleotide polymorphisms with the risk of PD in Chinese
      population. We performed a case-control association study, and 1189 subjects
      comprising 652 PD patients and 537 controls were genotyped by using a Mass ARRAY
      System or a TaqMan assay. We found that rs601999 (OR (95% CI) = 3.378 (2.273
      5.051), p < 0.001), rs11343 (OR (95% CI) = 0.426 (0.210-0.862), p = 0.018),
      rs353116 (OR (95% CI) = 0.738 (0.577-0.943), p = 0.015), and rs2280104 (OR (95%
      CI) = 1.371 (1.078-1.743), p = 0.010) were significantly associated with PD in
      Chinese population. However, no significant association was found in the
      remaining 13 single-nucleotide polymorphisms between both groups.

PMID- 30293727
TI  - Safety of Radioembolization in the Setting of Angiographically Apparent
      Arterioportal Shunting.
AB  - PURPOSE: To retrospectively analyze adverse events (AE) in patients with
      hepatocellular carcinoma (HCC) treated with yttrium-90 radioembolization in the
      setting of angiographically apparent arterioportal shunts (APSs). MATERIALS AND
      METHODS: Thirty-two patients with HCC underwent radioembolization with APSs from
      January 2011 to September 2016, totaling 34 administrations using resin (6) and
      glass (28) microspheres. APSs were graded angiographically as segmental (9),
      ipsilobar (15), contralobar (7), or main portal (2), according to portal
      perfusion. Tumors were categorized as solitary (9), multifocal (7), or
      infiltrative (16). Both unilobar (25) and bilobar (7) disease was treated. Child
      Pugh Score was A (22), B (10), or C (2), with a median Model for End-Stage Liver
      Disease (MELD)/Na-MELD of 8/8.5. Median procedure dose was 132.6 Gy. AEs were
      graded using Combined Terminology Criteria for Adverse Events (CTCAE) version
      4.0. Tumor response was assessed using the modified Response Evaluation Criteria
      in Solid Tumors (mRECIST). RESULTS: CTCAE grade >=3 AEs were observed in 22% of
      patients. Barcelona Clinic Liver Cancer (BCLC) C patients with nonsegmental
      shunts who received lobar administrations had a grade >=3 AE rate of 38% compared
      with the remaining cohort, which was 12% (P = .076). No events were reported in
      patients with segmental shunts (P = .023). Imaging analysis revealed mRECIST
      complete response (17), partial response (13), stable disease (3), and
      progressive disease (1). Overall survival at 6 months and 12 months was 72% and
      57%, respectively. CONCLUSIONS: Radioembolization in the setting of APS may have
      a higher AE profile than reported literature when BCLC-C patients with
      nonsegmental shunts receive lobar administrations. Segmental shunts are generally
      well tolerated.

PMID- 30293726
TI  - A Comparison between Prethoracoscopy Localization of Small Pulmonary Nodules by
      Means of Medical Adhesive versus Hookwire.
AB  - PURPOSE: To compare prethoracoscopy localization of small pulmonary nodules
      (SPNs) by means of medical adhesive versus hookwire. MATERIALS AND METHODS: One
      hundred seven patients who underwent video-assisted thoracoscopic surgery
      resection for SPNs were consecutively recruited in this retrospective cohort
      study. Patients were divided into 2 groups according to the material used for
      localization of the SPNs: the medical adhesive group (n = 88) and the hookwire
      group (n = 19). The baseline data were collected, and operation waiting time
      (OWT; the time gap between localization and surgery), wedge resection performing
      time (WRPT), pathologic result, and complications of the 2 groups were assessed.
      RESULTS: All SPNs were successfully marked. No differences in pathologic result
      (P = .676), wedge resection, or segmentectomy rate (P = .679) were observed. OWT
      was markedly longer in the medical adhesive group than in the hookwire group (P <
      .001), whereas WRPT was similar in the 2 groups (P = .926). There were
      significantly (P = .004) fewer complications in the medical adhesive group
      (37.42%) than in the hookwire group (15.79%). Regarding individual complications,
      hemorrhage occurred significantly less in the medical adhesive group than in the
      hookwire group (9% vs 68%; P < .001), and no differences of cough, pneumothorax,
      or chest pain were found between the 2 groups (all P > .05). Multivariate
      logistic regression analysis further validated that hookwire was independently
      correlated with a higher risk of complication occurrence (P = .008) and
      hemorrhage occurrence (P < .001) compared with medical adhesive. CONCLUSIONS:
      Compared with hookwire, localization via medical adhesive can achieve a flexible
      time gap between localization and surgery. It also decreases the complication
      rate and increases convenience owing to no need for an anchor hook.

PMID- 30293728
TI  - Para-Axial Central Venous Stent Placement in Patients with Malignant Central
      Venous Obstruction with a Venous Port.
AB  - The authors performed a para-axial central venous stent (p-CVS) placement in 38
      patients and implanted the stent without having to remove the functioning port.
      No difficulties were experienced in catheter function with p-CVS. In-stent
      stenosis was seen in 6 of 24 patients in the p-CVS group and in 6 of 18 patients
      in the intrastent venous stent placement group (P = .333). No complications
      occurred in any patient with p-CVS when the venous port was removed. Thus, p-CVS
      can be an alternative way to insert a CVS in patients who already have a
      functioning venous port.

PMID- 30293729
TI  - Characterizing the Impact of Women in Academic IR: A 12-Year Analysis.
AB  - PURPOSE: To determine the representation of female interventional radiology (IR)
      investigators and elucidate possible gender-specific disparities. MATERIALS AND
      METHODS: We analyzed 4,884 original, peer-reviewed articles from 2006-2017 in the
      Journal of Vascular and Interventional Radiology and CardioVascular and
      Interventional Radiology. Data abstraction and statistical analysis were
      performed for first and senior author gender, citations, and grants. RESULTS: We
      found that 84% of first authors and 91.4% of senior authors were male (P < .01).
      No significant difference was observed versus expected in terms of author gender
      collaboration combinations (P = 1.00). Each year reflected a 0.3%-0.4% increase
      in articles published by women (first author: B-value: 0.3, P = .05; senior
      author: B-value: 0.4, P = .01). No difference was observed in citations or grants
      received between genders. Female authors received increasing citations and grants
      each year (citations: first author: B-value: 0.24, P = .05; senior author: B
      value: 0.16, P = .15; grants: B-value: 0.88, P = .02). CONCLUSIONS: Women are
      equally as productive as men as determined by metrics such as number of
      publications, citations, and grants and are proportionally represented in the
      literature. No data indicating collaborative or citation/grant discrimination
      were observed, suggesting that the academic IR community is inclusive of its
      female constituents and equally respects their research contributions. Based on
      the statistically significant increases in female authorship observed in this 12
      year study, this article reports encouraging trends for the future of women in
      interventional radiology.

PMID- 30293730
TI  - Duplicated Prostate Artery Central Gland Blood Supply: A Retrospective Analysis
      and Classification System.
AB  - Angiograms and cone-beam computed tomography scans of 36 consecutive prostate
      artery embolization patients (72 hemipelves) between October 2014 and February
      2018 were reviewed. The hemipelves were classified according to the presence of
      dual central gland (CG) blood supply and the pattern of vascularization: Type 1
      with a single CG blood supply (83.3%; n = 60); Type 2 with 2 independent CG
      arteries with overlapping territories (9.7%; n = 7); and Type 3 with 2
      independent CG arteries with isolated territories (7%; n = 5). Up to 20% of
      pelvic sides may have more than 1 independent CG prostate artery that should be
      searched for during prostate artery embolization.

PMID- 30293731
TI  - Comparison between Surgical and Endovascular Hemodialysis Arteriovenous Fistula
      Interventions and Associated Costs.
AB  - PURPOSE: To compare: (i) rate of arteriovenous fistula (AVF) interventions in
      both incident and prevalent end-stage kidney disease patients; (ii) their
      associated costs; and (iii) intervention-free survival between patients with
      surgical hemodialysis arteriovenous fistula (SAVF) versus those with an
      endovascularly created fistula (endoAVF). MATERIALS AND METHODS: Data from the
      United States Renal Data System (USRDS) were abstracted to determine the rate of
      AVF interventions performed in the first year and associated costs (based on
      Medicare payment rates) for SAVFs created from 2011 to 2013 in the incident and
      prevalent patient cohorts. Comparative data for endoAVF were obtained from the
      Novel Endovascular Access Trial (NEAT). Event rates, intervention-free survival,
      and costs were compared between endoAVF and SAVF cohorts after 1:1 propensity
      score (PS) matching. RESULTS: In the matched incident patients, the event rate
      was 0.74 per patient-year (PY) for endoAVF versus 7.22/PY for SAVF (P < .0001),
      with a difference in expenditures of $16,494. Similarly, in matched prevalent
      patients the event rate was 0.46/PY for endoAVF vs 4.10/PY for SAVF (P < .0001),
      resulting in a cost difference of $13,389. Time-to-event analysis showed that at
      1 year, 70% of endoAVF patients experienced freedom from intervention versus only
      18% of SAVF patients for incident patients; these numbers were 62% and 18% for
      endoAVF and SAVF prevalent patients, respectively (P < .0001 for both).
      CONCLUSIONS: Both incident and prevalent patients with endoAVF required fewer
      interventions and had lower costs within the first year compared with matched
      patients with SAVF.

PMID- 30293732
TI  - Single-Center Retrospective Review of Radiofrequency Wire Recanalization of
      Refractory Central Venous Occlusions.
AB  - PURPOSE: To retrospectively review the effectiveness and safety of radiofrequency
      (RF) wire recanalization of refractory central venous occlusions (CVOs) and
      compare recurrent and nonrecurrent CVOs in terms of patient and occlusion
      characteristics. MATERIALS AND METHODS: Twenty CVOs were treated in 18 patients
      (age 40 y +/- 13; 9 women) with 11 superior vena cava (SVC) or brachiocephalic
      vein occlusions (ie, supradiaphragmatic) and 9 inferior vena cava or iliac vein
      occlusions (ie, infradiaphragmatic). Indications included pain, edema,
      ulceration, and/or dialysis arteriovenous fistula dysfunction peripheral to the
      CVO(s). All patients had multiple venous thrombotic risk factors, including
      mechanical venous compression, endothelial injury, and/or coagulopathies. CVO
      traversal was first attempted with standard and advanced techniques before RF
      wire recanalization and followed up with computed tomographic venography and
      clinic visits approximately 1, 3, 6, and 12 months after treatment. RESULTS:
      Sixteen CVOs (80%) were successfully transversed and associated with symptom
      relief. One major complication occurred involving SVC perforation into the
      pericardial space. Primary CVO patency rate was 56% at a median follow-up of 14.1
      months (interquartile range [IQR], 9.2-20.0 mo). Recurrent CVOs tended to be
      infradiaphragmatic (71% vs 12% for supradiaphragmatic; P = .02), longer (12.9 cm
      +/- 10.0 vs 2.3 cm +/- 1.3; P < .01), and associated with implanted venous
      stents, filters, or cardiac pacer/defibrillator leads (86% vs 22%; P = .01).
      Median time to restenosis/occlusion was 1.5 months (IQR, 1.1-6.1 mo).
      CONCLUSIONS: RF wire recanalization is a relatively effective and safe option for
      refractory CVOs. Patients with longer, infradiaphragmatic CVOs associated with
      indwelling devices may require closer follow-up for CVO recurrence.

PMID- 30293733
TI  - Modified Rat Hepatocellular Carcinoma Models Overexpressing Vascular Endothelial
      Growth Factor.
AB  - PURPOSE: To compare tumor vascularity in 4 types of rat hepatocellular carcinoma
      (HCC) models: N1S1, vascular endothelial growth factor (VEGF)-transfected N1S1
      (VEGF-N1S1), McA-RH7777, and VEGF-transfected McA-RH7777 (VEGF-McA-RH777) tumors.
      MATERIALS AND METHODS: The N1S1 and McA-RH7777 cell lines were transfected with
      expression vectors containing cDNA for rat VEGF. Eighty-eight male Sprague-Dawley
      rats (weight range, 400-450 g) were randomly divided into 4 groups (ie, 22 rats
      per model), and 4 types of tumor models were created by using the N1S1, VEGF
      N1S1, McA-RH7777, and VEGF-McA-RH777 cell lines. Tumor vascularity was evaluated
      by perfusion computed tomography (CT), enzyme-linked immunosorbent assay of VEGF,
      CD34 staining, angiography, and Lipiodol transarterial embolization. Intergroup
      discrepancies were evaluated by Kruskal-Wallis test. RESULTS: Arterial perfusion
      (P < .001), portal perfusion (P = .015), total perfusion (P < .001), tumor VEGF
      level (P = .002), and microvessel density (MVD; P = .007) were significantly
      different among groups. VEGF-McA-RH7777 tumors showed the greatest arterial
      perfusion (46.7 mL/min/100 mL +/- 15.5), total perfusion (60.7 mL/min/100 mL +/-
      21.8), tumor VEGF level (3,376.7 pg/mL +/- 145.8), and MVD (34.50/00 +/- 7.5).
      Whereas most tumors in the N1S1, VEGF-N1S1, and McA-RH7777 groups showed
      hypovascular staining on angiography and minimal Lipiodol uptake after
      embolization, 5 of 6 VEGF-McA-RH7777 tumors (83.3%) presented hypervascular tumor
      staining and moderate to compact Lipiodol uptake. CONCLUSIONS: McA-RH7777 tumors
      were more hypervascular than N1S1 tumors, and tumor vascularity was enhanced
      further by VEGF transfection. Therefore, the VEGF-McA-RH7777 tumor is recommended
      to mimic hypervascular human HCC in rats.

PMID- 30293734
TI  - Feasibility of Boosted Radioembolization for Hepatocellular Carcinoma Larger than
      5 cm.
AB  - PURPOSE: To address the feasibility of yttrium-90 (90Y) glass microspheres
      administered at a boosted dose in large hepatocellular carcinomas (HCCs).
      MATERIALS AND METHODS: From July 2016 to August 2017, 20 patients who underwent
      90Y radioembolization for treatment-naive HCC met the following inclusion
      criteria: (i) nodular tumor, (ii) tumor size > 5 cm, (iii) Barcelona Clinic Liver
      Cancer stage A/B disease, (iv) target perfused tissue dose > 150 Gy, and (v) all
      tumors treated in 1 session of radioembolization. Follow-up radiologic findings
      and clinical outcomes were retrospectively reviewed until May 2018. Tumor
      response was determined per modified Response Evaluation Criteria In Solid
      Tumors. RESULTS: Mean total radiation activity infused was 4.96 GBq +/- 1.82
      (median, 4.88 GBq; range, 1.63-9.15 GBq). Mean target perfused tissue dose was
      263.5 Gy +/- 95.2 (median, 241.6 Gy; range, 156.2-550.6 Gy). The mean number of
      vials used per treatment was 4.15 +/- 1.4 (median, 4; range, 2-7). Complete
      response rates were 25% at 1 month and 60% at 3 months. Complete response of the
      primary index tumor was achieved in 16 patients (80%) based on best tumor
      response. Local progression-free survival and progression-free survival rates
      were 94.1% and 85.0% at 6 mo and 94.1% and 74.7% at 1 year, respectively. Four
      patients (20%) had symptomatic (n = 3) or asymptomatic (n = 1) benign biliary
      strictures. CONCLUSIONS: Radioembolization with a boosted dose in patients with
      large HCCs may show favorable tumor response, but with considerable biliary
      complications.

PMID- 30293735
TI  - Patient and Facility Demographics Related Outcomes in Early-Stage Non-Small Cell
      Lung Cancer Treated with Radiofrequency Ablation: A National Cancer Database
      Analysis.
AB  - PURPOSE: To determine facility and patient demographics associated with survival
      in early-stage non-small cell lung cancer (NSCLC) treated with radiofrequency
      (RF) ablation. MATERIALS AND METHODS: The National Cancer Database was queried
      for cases of stage 1a NSCLC treated with RF ablation without chemotherapy or
      radiotherapy from 2004 to 2014. High-volume centers (HVCs) were defined as the
      top 95th percentile of facilities by number of procedures performed. Overall
      survival (OS) was estimated with the Kaplan-Meier method, and comparisons between
      survival curves were performed with the log-rank test. Propensity score-matched
      cohort analysis was performed. P values less than .05 were considered
      statistically significant. RESULTS: In the final cohort, 967 cases were included.
      Estimated median survival and follow-up were 33.1 and 62.5 months, respectively.
      Of 305 facilities, 15 were determined to be HVCs, treating 13 or more patients
      from 2004 to 2014. A total of 335 cases (34.6%) were treated at HVCs. On
      multivariate Cox regression analysis, treatment at an HVC was independently
      associated with improved OS (hazard ratio [HR] = 0.766; P = .006). After
      propensity score adjustment, 1-, 3-, and 5-year OS was 89.8%, 51.2%, and 27.7%,
      respectively, for patients treated at HVCs, compared to 85.2%, 41.5%, and 19.6%,
      respectively, for patients treated at non-HVCs (P = .015). Increasing age (HR =
      1.012; P = .013) and higher T-classification (HR = 1.392; P < .001) were
      independently associated with worse OS. CONCLUSION: Patients with early-stage
      NSCLC treated with RF ablation at HVCs experienced a significant increase in OS,
      suggesting regionalization of lung cancer management as a means of improving
      outcomes.

PMID- 30293736
TI  - Shoulder loading reliability in seated able-bodied subjects.
AB  - Shoulder performance and sensorimotor control assessments help to identify
      shoulder instabilities and document the rehabilitation progress. Testing seated
      subjects in a position of hand prehension requires less controlled adjustments to
      maintain body balance in a clinically relevant situation. The objective of this
      work was to determine the test-retest repeatability of a novel shoulder stability
      test in seated subjects with the ipsi-lateral hand in prehension during four arm
      loading conditions. Able-bodied subjects were seated on a rigid chair fixed to a
      force plate. A horizontally and posteriorly directed force was applied to the
      hand for four 4 loading conditions ranging from 0 to 3 kg. Ten postural balance
      parameters were calculated from the center of pressure displacements and its
      corresponding free moments. Intra-class correlation coefficients were calculated
      for three consecutive trials and for four loading conditions. Generally, the
      intra-class correlations values increased gradually with the load and varied from
      0.727 to 0.948. Tz values increased non-linearly with the applied load. The test
      retest reliability of a new shoulder stability test in seated able-bodied
      subjects was high with sufficient loading (3 kg) and 3 trials.

PMID- 30293737
TI  - Vacuum pretreatment coupled to ultrasound assisted osmotic dehydration as a novel
      method for garlic slices dehydration.
AB  - This study investigated the effects of multi-frequency mode ultrasound and vacuum
      technology on the water loss (WL) of garlic slices during osmotic dehydration
      (OD), and their effects on the microstructure of garlic. A new method of OD for
      garlic slices was proposed - Vacuum pretreatment coupled to ultrasound assisted
      osmotic dehydration (VUOD). The results indicated that the WL of the garlic
      slices treated with VUOD (21.12%) was significantly (p < 0.05) higher than slices
      treated with normally OD (NOD) (10.67%), vacuum pretreatment OD (VOD) (14.18%),
      and multi-frequency mode ultrasound assisted OD (UOD) (11.20-13.56%). A mass
      transfer mechanism of VUOD was proposed. Low-field nuclear magnetic resonance
      results quantified the moisture migration in the vacuole, cytoplasm and
      intercellular space, and the cell wall of garlic cells. The quality properties
      (allicin content, surface color change and firmness) of VUOD treated garlic
      slices are predominately better than NOD, VOD and UOD treated samples.

PMID- 30293738
TI  - Ultrasonic assisted fabrication of first MoO3/copper complex bio-nanocomposite
      based on Sesbania sesban plant for green oxidation of alcohols.
AB  - MoO3 nanoparticles were obtained using Sesbania sesban. Novel Schiff base ligand
      and its nanocomplex of copper were synthesized under ultrasonic irradiation.
      First MoO3/Copper Schiff base complex nanocomposite (NMCS) based on this natural
      plant was prepared and characterized by TEM, SEM, AFM, FT-IR, TGA, EDAX and
      elemental analysis. Then atom-efficient and selective oxidation of alcohols using
      hydrogen peroxide catalyzed by NMCS bio-nanocomposite under ultrasonic
      irradiation was reported. Structurally diverse set of alcohols was transformed
      into desired aldehyde and ketone products with high conversion and excellent
      selectivity under solvent free conditions. Products were isolated easily from
      green media, and the catalyst could be reused six times without any appreciable
      decrease in catalytic activity and selectivity.

PMID- 30293739
TI  - The ultrasound thermal cracking for the tar-sand bitumen.
AB  - The influence of ultrasonic irradiation on the tar-sand bitumen in the process of
      thermal cracking with an inert atmosphere was investigated thoroughly. The
      product distribution and coke characteristic produced by the conventional thermal
      cracking (CTC) and ultrasound thermal cracking (UTC) were invested at the
      following condition: ultrasound frequency 20 kHz, ultrasonic power 2000 W,
      reaction time 2 h, reaction temperature from 400 to 440  degrees C. The result of
      the liquid products distribution indicated that UTC can significantly increase
      gasoline yield and diesel yield, and dramatically reduce VGO (Vacuum Gas Oil)
      yield and residuum (greater than 500  degrees C) yield. The analysis of gas
      products showed that there were no significant differences for the gas
      distribution between the two reactions (methods), indicating that reaction of UTC
      still conformed to a radical chain mechanism, but the ratio of olefin/paraffin
      was greatly reduced in the process of UTC, which was attributed to the hydrogen
      transfer reaction promoted by ultrasound. The result of the analysis by SEM, FT
      IR, Raman, XRD and Zeta potential demonstrated that there was a significant
      difference for the morphology of cokes produced by the two methods. Mesocarbon
      microbeads (MCMB) was discovered in the process of UTC, which should be due to
      that the polymerization of the free macro-radicals produced from PAHs (Polycyclic
      Aromatic Hydrocarbons) promoted by ultrasonic cavitation. In addition, it can be
      inferred that the viscosity of the second liquid phase was reduced by ultrasonic
      mechanical function through the breakage of the stack of asphaltene molecules
      cross-linked by van der Waals force. According to the mesophase theory, the
      ultrasound irradiation promoted the formation of the second liquid phase,
      extended its existence time and reduced its viscosity, resulting in the formation
      of MCMB controlled by the surface tension during the process of UTC.

PMID- 30293740
TI  - A survey of infection prevention and control practices among solid organ
      transplantation centers.
AB  - There are no standard guidelines for infection prevention and control practices
      among solid organ transplantation centers. To characterize the differences in
      infection prevention and control strategies, an electronic survey was performed
      in 2015 among members of American Society of Transplantation Infectious Diseases
      Community of Practice. These results highlight notable practice differences.

PMID- 30293741
TI  - Factors influencing seasonal influenza vaccination uptake among health care
      workers in an adult tertiary care hospital in Singapore: A cross-sectional
      survey.
AB  - BACKGROUND: This study aimed to evaluate the factors influencing seasonal
      influenza vaccination uptake among different health care professional groups.
      METHODS: A single-center, cross-sectional survey using a standardized anonymous,
      self-administered questionnaire to assess knowledge, attitudes, and uptake of
      seasonal influenza vaccination was used. Associations between respective health
      care groups and vaccination acceptance were then assessed. RESULTS: In total,
      3,873 health care workers completed the questionnaire. Of these, 7% were
      administrative staff, 17% were allied health staff, 7% were ancillary staff, 11%
      were medical staff, and 58% were nursing staff. The overall vaccination rate for
      the Southern Hemisphere 2015 influenza season was 82%. In a multivariate logistic
      regression model, after controlling for gender and presence of chronic disease,
      associated factors for accepting influenza vaccination were age, education level
      of bachelor degree or higher, preference for vaccination provided by mobile
      teams, having 1-50 patient contacts per week, and belief in the potential
      severity of influenza and vaccine safety (P < .05). In contrast, factors
      negatively associated with vaccination acceptance included being a medical staff
      member or allied health staff member, living with family members under the age of
      16, fear of adverse reactions, and disbelief in vaccination effectiveness (P <
      .05). CONCLUSIONS: Although vaccine coverage in Singapore has been high, our
      findings provide guidance for the development of strategies to further improve
      vaccine coverage among different groups of health care workers.

PMID- 30293742
TI  - Shining a light on ultraviolet-C disinfection: No golden promises for infection
      prevention.

PMID- 30293743
TI  - Hands washing glove use, and avoiding recontamination before aseptic procedures
      at birth: A multicenter time-and-motion study conducted in Zanzibar.
AB  - BACKGROUND: Our primary objective was to assess hand hygiene (HH) compliance
      before aseptic procedures among birth attendants in the 10 highest-volume
      facilities in Zanzibar. We also examined the extent to which recontamination
      contributes to poor HH. Recording exact recontamination occurrences is not
      possible using the existing World Health Organization HH audit tool. METHODS: In
      this time-and-motion study, 3 trained coders used WOMBATv2 software to record the
      hand actions of all birth attendants present in the study sites. The percentage
      compliance and 95% confidence intervals (CIs) for individual behaviors (hand
      washing/rubbing, avoiding recontamination and glove use) and for behavioral
      sequences during labor and delivery were calculated. RESULTS: We observed 104
      birth attendants and 781 HH opportunities before aseptic procedures. Compliance
      with hand rubbing/washing was 24.6% (95% CI, 21.6-27.8). Only 9.6% (95% CI, 7.6
      11.9) of birth attendants also donned gloves and avoided recontamination. Half of
      the time when rubbing/washing or glove donning was performed, hands were
      recontaminated prior to the aseptic procedure. CONCLUSIONS: In this study, HH
      compliance by birth attendants before aseptic procedures was poor. To our
      knowledge, this is the first study in a low- to middle-income country to show the
      large contribution to poor HH compliance from hand and glove recontamination
      before the procedure. Recontamination is an important driver of infection risk
      from poor HH. It should be understood for the purposes of improvement and
      therefore included in HH monitoring and interventions.

PMID- 30293744
TI  - Oral caffeine administered during late gestation increases gestation length and
      piglet temperature in naturally farrowing sows.
AB  - Selection of sows for large litter size has adverse consequences including lesser
      and more variable birth weights, reduced piglet viability and greater peri- and
      post-natal piglet mortality. One approach to improve survival might be to feed
      caffeine to the sow, which improves piglet viability after induced farrowing, but
      has not been evaluated in sows which farrow naturally. Large White x Landrace
      sows were fed 0 (CON: n = 30) or 6 g/day caffeine (CAF: n = 34) with their daily
      feed from 3 days before expected parturition until farrowing. Numbers of piglets
      born alive and stillborn, as well as piglet vitality and meconium staining score
      were recorded at birth. Piglet rectal temperature was measured at 3 and 24 h and
      piglet survival was recorded through lactation. Compared with CON animals, sows
      of the CAF group had longer gestations (CON: 115.6 +/- 0.3 days; CAF: 116.6 +/-
      0.3 days, P = 0.01) and piglets of CAF sows had greater rectal temperatures 3 h
      after birth (CON: 37.6 +/- 0.2  degrees C, CAF 38.0 +/- 0.2  degrees C, P<0.05).
      Although there was no difference in the stillborn numbers per litter fewer CAF
      sows delivered stillborn piglets when compared to CON sows (CON: 43.3%, CAF:
      20.6%, P = 0.05). Piglet survival to day 18 of lactation was not altered by
      treatment (CON: 90.4 +/- 3.2%, CAF: 92.0 +/- 2.4%, P>0.05). The current data
      suggest that maternal supplementation with caffeine is a promising treatment to
      prevent premature farrowing and increase piglet temperature at birth, and may
      decrease the incidence of litters with stillborn piglets.

PMID- 30293746
TI  - Corrigendum.

PMID- 30293745
TI  - Triangular "shark fin-like" ST modification in takotsubo syndrome: Challenging
      the concept of ST-elevation patterns without coronary occlusion?

PMID- 30293747
TI  - Extracellular DAMPs in Plants and Mammals: Immunity, Tissue Damage and Repair.
AB  - Innate immune receptors, well known mediators of response to non-self-molecules
      and inflammation, also act as mediators of immunity triggered by 'damage
      associated molecular patterns' (DAMPs). Pathogen-associated molecular patterns
      (PAMPs) cause inflammation in mammals and a rapid immune response in plants,
      while DAMPs trigger more complex responses, including immunity, tissue
      maintenance and repair. DAMPs, their receptors and downstream transduction
      mechanisms are often conserved within a kingdom or, due to convergent evolution,
      are similar across the kingdoms of life. Herein, we describe the dynamics and
      functionality of specific extracellular DAMP classes and their receptors in
      immunity, inflammation and repair of tissue damage in plants and mammals.

PMID- 30293748
TI  - Comparison of the clinical effectiveness of Bone Morphogenic Protein (BMP) -2 and
      -7 in the adjunct treatment of lower limb nonunions.
AB  - BACKGROUND: Substantial evidence exists demonstrating the individual
      effectiveness of both rhBMP-2 and -7 in the treatment of nonunions, data
      comparing the clinical effectiveness of adjunct rhBMP-2 and -7 remains scarce.
      Therefore, we examined our large single-center case series to compare the
      clinical effectiveness of both rhBMP-2 and -7 in non-union therapy aiming to
      answer: - Does a certain type of BMP have an advantageous effect on radiological
      outcome of applied lower limb non-union therapy? - Does application of a certain
      type of BMP have an advantageous effect on radiological outcome of infected lower
      limb nonunions? - Are there any additional risk factors associated with inferior
      outcome in context with an adjunct BMP treatment? HYPOTHESIS: Both BMPs have the
      same effect on the radiological outcome of surgically treated lower limb
      nonunions. PATIENTS AND METHODS: Single-center retrospective database analysis of
      a case series of patients with lower limb long bone nonunions receiving either a
      one- or two-stage (Masquelet-) procedure based on the "diamond concept" with
      application of rhBMP-2 or -7. The "diamond concept" summarizes core factors that
      need to be present to achieve bone healing. In particular, these factors relate
      to the optimization of the mechanical (stability) and biological environment
      (sufficient osteogenic and angiogenic cells, osteoconductive scaffolds and growth
      factors). All medical data from patients that received surgical treatment between
      01/01/2010 and 31/12/2016 were assessed. In total, 356 patients were treated with
      BMPs and 156 patients 18 years or older with non-union of their tibia or femur
      having a follow-up of at least 1 year were included. Consolidation in context
      with type of rhBMP was compared and the influence of relevant risk factors
      assessed. RESULTS: Consolidation rate was significantly higher in patients
      treated with rhBMP-2 (rhBMP-2: 42/46 (91%) vs. rhBMP-7: 64/110 (58%); p<0.001).
      In particular, application of rhBMP-2 increased the likelihood of consolidation
      for tibial nonunions (OR 32.744; 95%CI: 2.909-368.544; p=0.005) and when used in
      two-stage therapy (OR 12.095; 95% CI: 2.744-53.314; p=0.001). Furthermore,
      regression modeling revealed a higher correlation between application of rhBMP-2
      and osseous consolidation in infected nonunions (OR 61.062; 95% CI: 2.208
      1688.475; p=0.015) than in aseptic nonunions (OR 4.787; 95% CI: 1.321-17.351;
      p=0.017). Risk factors negatively influencing the outcome of non-union treatment
      in context with rhBMPs were identified as active smoking (OR 0.357; 95% CI: 0.138
      0.927; p=0.024), atrophic nonunion (OR 0.23; 95% CI: 0.061-0.869; p=0.030),
      higher BMI (OR 0.919; 95% CI: 0.846-0.998; p=0.046) and a larger defect size (OR
      0.877; 95% CI: 0.784-0.98; p=0.021). DISCUSSION: Patients who received rhBMP-2
      for the treatment of tibial nonunions and as part of the two-stage treatment had
      a significantly higher rate of healing compared to patients treated with rhBMP-7
      regardless of infection. LEVEL OF EVIDENCE: III, retrospective case-control
      study.

PMID- 30293749
TI  - New scoring system at admission to predict walking ability at discharge for
      patients with hip fracture.
AB  - INTRODUCTION: A reliable scoring system that predicts the walking ability of hip
      fracture patients would be useful for clinicians. Here we developed a scoring
      system for hip fracture patients and evaluated its predictive ability.
      HYPOTHESIS: We hypothesized that age, sex, presence of dementia, walking ability
      before the injury, fracture type, serum hemoglobin level, serum albumin level and
      interval in days between admission and surgery would be the predictive factors of
      the walking ability at discharge. MATERIAL AND METHODS: Data from 409 patients
      who underwent hip fracture surgery were included. We analyzed factors that
      affected walking ability and developed a scoring system that predicts the
      probability of walking unaided or with a cane at discharge. RESULTS: The mean age
      of the patients was 81.3 years. A total of 164 (40%) patients could walk unaided
      or with a cane at discharge. Multivariate logistic regression analysis showed
      that the obstructive factors for the ability to walk unaided or with a cane at
      discharge were older age (odds ratio [OR]=0.962, p=0.002), dementia (OR=0.126,
      p<0.001), use of a cane before injury (OR=0.396, p<0.001), trochanteric fracture
      (OR=0.571, p=0.027) and low serum albumin level (OR=4.15, p<0.001) at admission.
      The scoring system used the following formula: Score=5-0.04*age+albumin-2(with
      dementia)- 1(with use of a cane before injury)-1(with trochanteric fracture). The
      C-statistics for the scoring system was 0.81 (95% confidence interval, 0.77
      0.85). DISCUSSION: This newly developed scoring system of information at
      admission predicted the discharge mobility of hip fracture patients. In addition
      to the previously known risk factors, serum albumin level at admission was
      detected as a new predictor for mobility at discharge. LEVEL OF PROOF: IV,
      retrospective study.

PMID- 30293750
TI  - Fibular non-union in distraction osteogenesis of the tibia.
AB  - INTRODUCTION: There is concern regarding potential non-union of the fibula
      following distraction osteogenesis and if non-union of the fibula leads to poor
      outcome. HYPOTHESIS: Assess the incidence of fibula non-union in patients
      undergoing distraction osteogenesis of the tibia and to report the effects on
      patient outcome. We also describe the management of this complication. MATERIALS
      AND METHODS: A consecutive series of patients undergoing distraction osteogenesis
      at a tertiary centre under a single surgeon. The amount of distraction, site of
      osteotomy, union of the fibula and tibia were recorded. RESULTS: Fifty-eight
      distraction procedures. Mean age was 37.2, 36 males and 22 females. Mean follow
      up 23.4 months. 49 (84.5%) achieved fibula union at frame removal, and 9 (15.5%)
      went on to non-union. Of the fibulas that united, the mean lengthening was
      9.25mm. In fibula non-union there was significantly greater lengthening (23.66mm)
      (p=0.004). Fifty-four (93.1%) of the tibias united following osteotomy and
      distraction, whilst 4 (6.9%) went onto non-union requiring operative treatment.
      Of the 4 tibias that did not unite, 3 (75%) also had fibula non-union (p=0.01).
      Three (33.3%) of the 9 fibulas that did not unite developed symptoms. Two of
      these required surgery in the form of fibula plating. Both of these patient's
      symptoms resolved following surgery. DISCUSSION: Fibula non-union is a relatively
      common complication following osteotomy in distraction osteogenesis. The length
      of fibula distraction and tibia non-union are significant risk factors. We
      recommend surgical intervention for those patients who have symptomatic fibula
      non-unions. LEVEL OF EVIDENCE: IV, case series.

PMID- 30293751
TI  - Total hip arthroplasty after failed transtrochanteric rotational osteotomy for
      osteonecrosis of the femoral head: A systematic review and meta-analysis.
AB  - BACKGROUND: Several studies have reported regarding total hip arthroplasty (THA)
      for osteonecrosis of the femoral head after failed transtrochanteric rotational
      osteotomy (TRO). However, to our knowledge, no formal systematic review and meta
      analysis have been published yet summarizing the clinical results of a THA after
      failed TRO. Therefore, we conducted a systematic review and meta-analysis of the
      THA outcomes after failed TRO. We focussed on the issue whether a previous TRO
      affects the results of subsequent THA, including operative time, operative blood
      loss, radiological parameters, postoperative complications, and clinical
      outcomes. METHODS: Literatures published up to January 2018 were searched in the
      PubMed, Web of Science, and Cochrane Library, and the pooling of data was
      performed using a RevMan software (version 5.3, Cochrane Collaboration, Oxford,
      UK). A p-value<0.05 was considered statistically significant. We calculated the
      mean differences (MD) for continuous data and the odds ratio (OR) for dichotomous
      data with 95% confidence intervals (CI) for each outcome. Statistical
      heterogeneity was assessed based on I2 using the standard Chi2. When I2>50%,
      significant heterogeneity was assumed, and a random-effects model was applied for
      the meta-analysis. A fixed-effects model was applied in the absence of
      significant heterogeneity. RESULTS: Five studies were included in this meta
      analysis. The results showed that operative time was significantly longer in the
      THA after the TRO than that for the THA without previous osteotomy (I2=92%;
      MD=31.62; 95% CI: 5.95 to 57.28; p=0.02). Operative blood loss was significantly
      greater in the THA after the TRO than that in the THA without previous osteotomy
      (I2=71%; MD=123.30; 95% CI: 22.21 to 224.39; p=0.02). The rate of stem
      malalignment was significantly higher in the THA after the TRO than that in the
      THA without previous osteotomy (I2=0%; OR=5.23, 95% CI: 1.95 to 14.06; p=0.001).
      There was no significant difference in the dislocation rate (I2=0%; OR=2.12; 95%
      CI: 0.64 to 6.99; p=0.22), and the postoperative Harris hip score at the final
      follow-up (I2=75%, MD=-0.46, 95% CI: -3.92 to 3.01, p=0.80) between the groups.
      CONCLUSION: The results demonstrate that, performing the THA after the TRO is
      technically more demanding than the THA without previous osteotomy. TRO does not
      affect the clinical results of future THA, and is a sufficient therapeutic
      alternative in younger patients. LEVEL OF EVIDENCE: III, systematic and meta
      analysis of case control studies.

PMID- 30293752
TI  - Mast Cells in Neuroimmune Interactions.
AB  - A major aspect of the regulatory function of mast cells appears to be their role
      as intermediaries between the nervous and immune systems. Mast cells are
      activated by neurotransmitters allowing neural control of innate and adaptive
      immunity. Conversely, mast cells secrete mediators including neurotransmitters
      and neurotrophic factors that directly influence nerves, causing acute activation
      and/or long-lasting changes in excitability and phenotype. While some basic
      mechanisms underlying mast cell-nerve communication are well-established, the
      full extent to which this relationship influences health and disease is unclear.
      Future studies of mast cell-nerve interactions may provide greater understanding
      of how immune and nervous systems coordinate multiple aspects of homeostatic
      control, and will potentially offer therapeutic targets in both immune and
      neurological disorders.

PMID- 30293753
TI  - The Usefulness of Practical Training in Awareness and Preference for the
      Respiratory Medicine Speciality among Undergraduate Students.

PMID- 30293754
TI  - Outcomes of Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell
      Transplantation for Hodgkin Lymphomas: A Retrospective Multicenter Experience by
      the Rete Ematologica Pugliese (REP).
AB  - BACKGROUND: Hodgkin lymphoma (HL) is a potentially curable disease, and modern
      therapy is expected to successfully cure more than 80% of the patients. However,
      patients progressing after intensive treatments, such as autologous stem cell
      transplantation (SCT), have a very poor outcome. Allogeneic SCT offers the only
      strategy with a curative potential for these patients. This study reports a
      retrospective multicenter experience of the Rete Ematologica Pugliese (REP) over
      the past 17 years, aiming to define the impact of each patient's disease and
      transplant-related characteristics on outcomes. PATIENTS AND METHODS: We
      retrospectively studied 72 patients with HL who received allogeneic SCT from 2000
      to 2017. At the time of allogeneic SCT, 33 (46%) patients had chemosensitive
      disease, and 39 (54%) were chemo-refractory. All patients received reduced
      intensity conditioning, 50% received grafts from a matched sibling donor, and 50%
      from a matched-unrelated donor. RESULTS: With a median follow-up of 48 months
      (range, 3-195 months), 30 patients are alive, and 42 have died. The Kaplan-Meier
      estimates of overall survival and progression-free survival at 5 years were 35%
      and 34%, respectively. Following transplantation, 12 (17%) patients died of non
      relapse mortality at a median of 90 days (range, 1 day-20 months). The causes of
      death included infection (n = 7), graft-versus-host disease (n = 3), and multi
      organ failure (n = 2). CONCLUSIONS: Allogeneic SCT results extend survival in
      selected patients with relapsed/refractory HL, showing low treatment-related
      mortality. Patients with active disease at the time of allogeneic transplantation
      have poor outcomes. Allogeneic SCT may be an effective salvage strategy for
      patients who relapse after an autologous SCT.

PMID- 30293755
TI  - Corrigendum to "Primary Total Knee Arthroplasty in Patients With Neuropathic
      (Charcot) Arthropathy: Contemporary Results" [Journal of Arthroplasty 33 (2018)
      2815-2820].

PMID- 30293756
TI  - What Is the Role of Repeat Aspiration in the Diagnosis of Periprosthetic Hip
      Infection?
AB  - BACKGROUND: The American Academy of Orthopedic Surgeons clinical practice
      guideline currently recommends repeat joint aspiration when workup of
      periprosthetic joint infection (PJI) reveals conflicting data. This guideline is
      based on a single study of 31 patients published 25 years ago. We sought to
      determine the correlation between first and second aspirations and factors that
      may play a role in variability between them. METHODS: Sixty patients with less
      than 90 days between aspirations and no intervening surgery were identified at
      our institution and classified by Musculoskeletal Infection Society (MSIS)
      criteria as infected, not infected, or not able to determine after both
      aspirations. Culture results from both aspirations were recorded. The rates of
      change and correlation in clinical diagnosis and culture results between
      aspirations were determined. RESULTS: Repeat aspiration changed the diagnosis in
      26 cases (43.3%, 95% confidence interval 31.6-55.9, kappa coefficient 0.32, P <
      .001), and the culture results in 25 cases (41.7%, 95% confidence interval 30.1
      54.3, kappa coefficient 0.27, P < .01). Among patients initially MSIS negative,
      the proportion who changed to MSIS positive was greater for those with a history
      of prior PJI compared to those without (66.7% vs 0%, P < .05), and the first
      aspiration mean volume was higher for those changed to MSIS positive compared to
      those that remained MSIS negative (12.0 vs 3.0 mL, P < .01). Among patients
      initially MSIS positive, the proportion of patients who changed to MSIS negative
      was greater for those with a history of adverse local tissue reaction (ALTR) to
      metal debris compared to patients without suspicion of ALTR (100% vs 7.7%, P <
      .05). CONCLUSION: Repeat aspiration is particularly useful in patients with
      conflicting clinical data and prior history of PJI, suspicion of ALTR, or with
      high clinical suspicion of infection.

PMID- 30293757
TI  - Wandering spleen and intestinal malrotation.

PMID- 30293758
TI  - First PIPAC treatment in a Spanish public hospital: A novel technique for the
      treatment of carcinomatosis.

PMID- 30293759
TI  - Acute gastrointestinal bleeding, multiple GIST and intestinal ganglioneuromatosis
      in a patient with neurofibromatosis.

PMID- 30293760
TI  - [Evaluation of infectious prevention practices in myeloma].

PMID- 30293761
TI  - The diversity of the proline-rich domain of pneumococcal surface protein A
      (PspA): Potential relevance to a broad-spectrum vaccine.
AB  - Pneumococcal surface protein A (PspA) is a surface exposed, highly immunogenic
      protein of Streptococcus pneumoniae. Its N-terminal alpha-helical domain
      (alphaHD) elicits protective antibody in humans and animals that can protect mice
      from fatal infections with pneumococci and can be detected in vitro with
      opsonophagocytosis assays. The proline-rich domain (PRD) in the center of the
      PspA sequence can also elicit protection. This study revealed that although the
      sequence of PRD was diverse, PRD from different pneumococcal isolates contained
      many shared elements. The inferred amino acid sequences of 123 such PRDs, which
      were analyzed by assembly and alignment-free (AAF) approaches, formed three PRD
      groups. Of these sequences, 45 were classified as Group 1, 19 were classified as
      Group 2, and 59 were classified as Group 3. All Group 3 sequences contained a
      highly conserved 22-amino acid non-proline block (NPB). A significant
      polymorphism was observed, however, at a single amino acid position within NPB.
      Each of the three PRD groups had characteristic patterns of short amino acid
      repeats, with most of the repeats being found in more than one PRD group. One of
      these repeats, PKPEQP as well as the NPB were previously shown to elicit
      protective antibodies in mice. In this study, we found that sera from 12 healthy
      human adult volunteers contained antibodies to all three PRD groups. This
      suggested that a PspA-containing vaccine containing carefully selected PRDs and
      alphaHDs could redundantly cover the known diversity of PspA. Such an approach
      might reduce the chances of PspA variants escaping a PspA vaccine's immunity.

PMID- 30293762
TI  - Non-clinical safety assessment of repeated intramuscular administration of an EV
      A71 VLP vaccine in rabbits.
AB  - A candidate hand, foot, and mouth disease vaccine comprising of human enterovirus
      A71 (EV-A71) virus-like particles (VLPs) was tested in rabbits to evaluate the
      potential local and systemic effects of this vaccine. The rabbits received more
      than double the full human dose and one additional dose according to the n + 1
      recommended scheme. The three doses were given mixed with Alhydrogel adjuvant as
      intramuscular (IM) injections. Vaccinations were well-tolerated, with no
      indication of overt toxicity in any parameter observed. An EV-A71 specific immune
      response in the form of antibodies that specifically reacted with the virus
      capsid proteins VP1 and VP0, the complete VLP, and EV-A71 viruses of different
      subgenotypes to that of the vaccine could be demonstrated. A boosting effect in
      the form of higher EV-A71 specific antibody titers was observed after the
      subsequent doses, and these enhanced titers were shown to be statistically
      significant in one-way ANOVA analyses. Fortnightly intramuscular administration
      of EV-A71 VLP vaccine did not result in any test article-related changes in
      immunotoxicity as defined by increased serum IL-6, and in general IL-6
      concentrations remained below the lower limit of quantitation for the majority of
      animals throughout the study. Although increased indicators of inflammation at
      the injection site were observed in animals sacrificed immediately after the last
      vaccination, these largely reversed at the end of the recovery phase. No findings
      suggestive of systemic or delayed toxicity were recorded in this independently
      conducted study. In conclusion, repeated IM administration of the EV-A71 VLP
      vaccine were locally and systemically well-tolerated in rabbits and immunogenic,
      supporting the clinical development of the vaccine.

PMID- 30293763
TI  - Co-delivery of amphipol-conjugated adjuvant with antigen, and adjuvant
      combinations, enhance immune protection elicited by a membrane protein-based
      vaccine against a mucosal challenge with Chlamydia.
AB  - INTRODUCTION: Chlamydial infections are spread worldwide and a vaccine is needed
      to control this pathogen. The goals of this study were to determine if the
      delivery of an adjuvant associated to the antigen, via a derivatized amphipol,
      and adjuvant combinations improve vaccine protection. METHODS: A novel approach,
      trapping the Chlamydia muridarum (Cm) native MOMP (nMOMP) with amphipols (A8-35),
      bearing a covalently conjugated peptide (EP67), was used. Adjuvants incorporated
      were: EP67 either conjugated to A8-35, which was used to trap nMOMP (nMOMP/EP67
      A8-35), or free as a control, added to nMOMP/A8-35 complexes (nMOMP/A8-35+EP67);
      Montanide ISA 720 to enhance humoral responses, and CpG-1826 to elicit robust
      cell-mediated immunity (CMI). BALB/c mice were immunized by mucosal and systemic
      routes. Intranasal immunization with live Cm was used as positive control and
      three negative controls were included. Mice were challenged intranasally with Cm
      and changes in body weight, lungs weight and number of Cm-inclusion forming units
      (IFU) recovered from the lungs were evaluated to establish protection. To assess
      local responses levels of IFN- gamma and Cm-specific IgA were determined in
      lungs' supernatants. RESULTS: Structural assays demonstrated that nMOMP secondary
      structure and thermal stability were maintained when A8-35 was covalently
      modified. Mice vaccinated with nMOMP/EP67-A8-35 were better protected than
      animals immunized with nMOMP/A8-35+EP67. Addition of Montanide enhanced Th2
      responses and improved protection. Including CpG-1826 further broadened,
      intensified and switched to Th1-biased immune responses. With delivery of nMOMP
      and the three adjuvants, as determined by changes in body weight, lungs weight
      and number of IFU recovered from lungs, protection at 10 days post-challenge was
      equivalent to that induced by immunization with live Cm. CONCLUSIONS: Covalent
      association of EP67 to A8-35, used to keep nMOMP water-soluble, improves
      protection over that conferred by free EP67. Adjuvant combinations including
      EP67+Montanide+CpG-1826, by broadening and intensifying cellular and humoral
      immune responses, further enhanced protection.

PMID- 30293764
TI  - Mitigating bias in observational vaccine effectiveness studies using simulated
      comparator populations: Application to rotavirus vaccination in the UK.
AB  - BACKGROUND: Measuring vaccine effectiveness (VE) relies on the use of
      observational study designs. However, achieving robust estimates of direct and
      indirect VE is frequently compromised by bias, particularly when using syndromic
      diagnoses of low-specificity. METHODS: In order to mitigate confounding between
      the measured outcome and vaccine uptake, we developed a method to balance
      comparator populations using individual-level propensity scoring derived from the
      vaccine-exposed population, and applied it to the unexposed comparator
      population. Indirect VE was estimated by comparing the unvaccinated vaccine
      exposed group with a propensity score-simulated unvaccinated, unexposed group.
      Direct VE was derived by removing indirect VE from the overall VE. We applied
      this method to an evaluation of the effectiveness of infant rotavirus vaccination
      in the UK. Using a general practice cohort of 45,259 live births between May 2010
      and December 2015, we calculated indirect and direct VE against consultations for
      acute gastroenteritis using conventional and vaccination-propensity adjustment
      comparator populations. RESULTS: The overall VE during the rotavirus-season
      (January-May) calculated using mixed-effects Cox regression was 30% [95%
      confidence intervals (95% CI: 25,35%)]. Use of conventional comparator
      populations resulted in implausible VE estimates -14% (95% CI: -41,7%) for direct
      and 29% (95% CI: 14,42%) for indirect effects. Applying our alternative method,
      direct VE was 26% (95% CI: 1,45%) and indirect VE was 8% (95% CI: -19,29%).
      CONCLUSIONS: Estimating VE using propensity score simulated comparator
      populations, particularly for studies using routine health data with syndromic,
      low-specificity endpoints will aid accurate measurement of the broader public
      health impact of a vaccine programme.

PMID- 30293765
TI  - Cost-effectiveness analysis of maternal immunisation against group B
      Streptococcus (GBS) disease: A modelling study.
AB  - BACKGROUND: There is a considerable global burden of invasive group B
      streptococcal (GBS) disease. Vaccines are being developed for use in pregnant
      women to offer protection to neonates. OBJECTIVE: To estimate the potential
      impact and cost-effectiveness of maternal immunisation against neonatal and
      maternal invasive GBS disease in the UK. METHODS: We developed a decision-tree
      model encompassing GBS-related events in infants and mothers, following a birth
      cohort with a time horizon equivalent to average life expectancy (81 years). We
      parameterised the model using contemporary data from disease surveillance and
      outcomes in GBS survivors. Costs were taken from NHS sources and research
      studies. Maternal immunisation in combination with risk-based intrapartum
      antibiotic prophylaxis (IAP) was compared to the current standard practice of
      risk-based IAP alone from an NHS and Personal Social Services (health-provider)
      perspective. We estimated the cases averted and cost per QALY gained through
      vaccination. One-way sensitivity analysis, scenario analysis and probabilistic
      sensitivity analysis were performed. RESULTS: An effective maternal immunisation
      programme could substantially reduce the burden of GBS disease. The deterministic
      analysis estimated the threshold cost-effective price for a GBS vaccine to be L54
      per dose at L20,000/QALY (L71 per dose at L30,000/QALY). Results were most
      sensitive to assumptions on disease incidence, sequelae rate and vaccine
      efficacy. Probabilistic analysis showed 90.66% of iterations fell under the
      L30,000 threshold at a vaccine price of L55. Inclusion of modest prevention of
      stillbirths and/or, preterm births, carer health impacts, maternal GBS deaths and
      1.5% discounting improved cost-effectiveness compared to the base case. Lowering
      vaccine strain coverage made the vaccine less cost-effective. A key limitation is
      that the properties of the final GBS vaccine are unknown. CONCLUSIONS: Maternal
      GBS immunisation is expected to be cost-effective, even at a relatively high
      vaccine price.

PMID- 30293766
TI  - CYTED Network to develop an immunogen compatible with integrated management
      strategies for tick control in cattle.
AB  - INCOGARR is a thematic network recently approved to be financially supported by
      the Ibero-American Program of Science and Technology for Development (CYTED). The
      objectives of this Network are the design and evaluation of an efficient and
      feasible anti-tick vaccine candidate from the technical and economical points of
      view and also sharing experiences in the immunological control of ticks as part
      of an Integrated Control Program. The Network consists of seven laboratories and
      one company from six countries. The first meeting of the Network took place with
      the representation of each laboratory involved. In the meeting, general and
      specific objectives and activities of the Network were discussed and it was a
      very nice example of international collaboration to address an unsolved worldwide
      topic on tick control in which laboratories with different competencies and
      expertise join their efforts in a common goal.

PMID- 30293767
TI  - Lipoprotein(a): lodestar for future clinical trials.

PMID- 30293768
TI  - Twice the benefits with twincretins?

PMID- 30293769
TI  - Baseline and on-statin treatment lipoprotein(a) levels for prediction of
      cardiovascular events: individual patient-data meta-analysis of statin outcome
      trials.
AB  - BACKGROUND: Elevated lipoprotein(a) is a genetic risk factor for cardiovascular
      disease in general population studies. However, its contribution to risk for
      cardiovascular events in patients with established cardiovascular disease or on
      statin therapy is uncertain. METHODS: Patient-level data from seven randomised,
      placebo-controlled, statin outcomes trials were collated and harmonised to
      calculate hazard ratios (HRs) for cardiovascular events, defined as fatal or non
      fatal coronary heart disease, stroke, or revascularisation procedures. HRs for
      cardiovascular events were estimated within each trial across predefined
      lipoprotein(a) groups (15 to <30 mg/dL, 30 to <50 mg/dL, and >=50 mg/dL, vs <15
      mg/dL), before pooling estimates using multivariate random-effects meta-analysis.
      FINDINGS: Analyses included data for 29 069 patients with repeat lipoprotein(a)
      measurements (mean age 62 years [SD 8]; 8064 [28%] women; 5751 events during 95
      576 person-years at risk). Initiation of statin therapy reduced LDL cholesterol
      (mean change -39% [95% CI -43 to -35]) without a significant change in
      lipoprotein(a). Associations of baseline and on-statin treatment lipoprotein(a)
      with cardiovascular disease risk were approximately linear, with increased risk
      at lipoprotein(a) values of 30 mg/dL or greater for baseline lipoprotein(a) and
      50 mg/dL or greater for on-statin lipoprotein(a). For baseline lipoprotein(a),
      HRs adjusted for age and sex (vs <15 mg/dL) were 1.04 (95% CI 0.91-1.18) for 15
      mg/dL to less than 30 mg/dL, 1.11 (1.00-1.22) for 30 mg/dL to less than 50 mg/dL,
      and 1.31 (1.08-1.58) for 50 mg/dL or higher; respective HRs for on-statin
      lipoprotein(a) were 0.94 (0.81-1.10), 1.06 (0.94-1.21), and 1.43 (1.15-1.76). HRs
      were almost identical after further adjustment for previous cardiovascular
      disease, diabetes, smoking, systolic blood pressure, LDL cholesterol, and HDL
      cholesterol. The association of on-statin lipoprotein(a) with cardiovascular
      disease risk was stronger than for on-placebo lipoprotein(a) (interaction
      p=0.010) and was more pronounced at younger ages (interaction p=0.008) without
      effect-modification by any other patient-level or study-level characteristics.
      INTERPRETATION: In this individual-patient data meta-analysis of statin-treated
      patients, elevated baseline and on-statin lipoprotein(a) showed an independent
      approximately linear relation with cardiovascular disease risk. This study
      provides a rationale for testing the lipoprotein(a) lowering hypothesis in
      cardiovascular disease outcomes trials. FUNDING: Novartis Pharma AG.

PMID- 30293770
TI  - Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in
      patients with type 2 diabetes: a randomised, placebo-controlled and active
      comparator-controlled phase 2 trial.
AB  - BACKGROUND: LY3298176 is a novel dual glucose-dependent insulinotropic
      polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that is
      being developed for the treatment of type 2 diabetes. We aimed to examine the
      efficacy and safety of co-stimulation of the GLP-1 and GIP receptors with
      LY3298176 compared with placebo or selective stimulation of GLP-1 receptors with
      dulaglutide in patients with poorly controlled type 2 diabetes. METHODS: In this
      double-blind, randomised, phase 2 study, patients with type 2 diabetes were
      randomly assigned (1:1:1:1:1:1) to receive either once-weekly subcutaneous
      LY3298176 (1 mg, 5 mg, 10 mg, or 15 mg), dulaglutide (1.5 mg), or placebo for 26
      weeks. Assignment was stratified by baseline glycated haemoglobin A1c (HbA1c),
      metformin use, and body-mass index (BMI). Eligible participants (aged 18-75) had
      type 2 diabetes for at least 6 months (HbA1c 7.0-10.5%, inclusive), that was
      inadequately controlled with diet and exercise alone or with stable metformin
      therapy, and a BMI of 23-50 kg/m2. The primary efficacy outcome was change in
      HbA1c from baseline to 26 weeks in the modified intention-to-treat (mITT)
      population (all patients who received at least one dose of study drug and had at
      least one postbaseline measurement of any outcome). Secondary endpoints, measured
      in the mITT on treatment dataset, were change in HbA1c from baseline to 12 weeks;
      change in mean bodyweight, fasting plasma glucose, waist circumference, total
      cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, and proportion
      of patients reaching the HbA1c target (<=6.5% and <7.0%) from baseline to weeks
      12 and 26; and proportion of patients with at least 5% and 10% bodyweight loss
      from baseline to 26 weeks. This study is registered with ClinicalTrials.gov,
      number NCT03131687. FINDINGS: Between May 24, 2017, and March 28, 2018, 555
      participants were assessed for eligibility, of whom 318 were randomly assigned to
      one of the six treatment groups. Because two participants did not receive
      treatment, the modified intention-to-treat and safety populations included 316
      participants. 258 (81.7%) participants completed 26 weeks of treatment, and 283
      (89.6%) completed the study. At baseline, mean age was 57 years (SD 9), BMI was
      32.6 kg/m2 (5.9), duration from diagnosis of diabetes was 9 years (6), HbA1c was
      8.1% (1.0), 53% of patients were men, and 47% were women. At 26 weeks, the effect
      of LY3298176 on change in HbA1c was dose-dependent and did not plateau. Mean
      changes from baseline in HbA1c with LY3298176 were -1.06% for 1 mg, -1.73% for 5
      mg, -1.89% for 10 mg, and -1.94% for 15 mg, compared with -0.06% for placebo
      (posterior mean differences [80% credible set] vs placebo: -1.00% [-1.22 to 
      0.79] for 1 mg, -1.67% [-1.88 to -1.46] for 5 mg, -1.83% [-2.04 to -1.61] for 10
      mg, and -1.89% [-2.11 to -1.67] for 15 mg). Compared with dulaglutide (-1.21%)
      the posterior mean differences (80% credible set) for change in HbA1c from
      baseline to 26 weeks with the LY3298176 doses were 0.15% (-0.08 to 0.38) for 1
      mg, -0.52% (-0.72 to -0.31) for 5 mg, -0.67% (-0.89 to -0.46) for 10 mg, and 
      0.73% (-0.95 to -0.52) for 15 mg. At 26 weeks, 33-90% of patients treated with
      LY3298176 achieved the HbA1c target of less than 7.0% (vs 52% with dulaglutide,
      12% with placebo) and 15-82% achieved the HbA1c target of at least 6.5% (vs 39%
      with dulaglutide, 2% with placebo). Changes in fasting plasma glucose ranged from
      -0.4 mmol/L to -3.4 mmol/L for LY3298176 (vs 0.9 mmol/L for placebo, -1.2 mmol/L
      for dulaglutide). Changes in mean bodyweight ranged from -0.9 kg to -11.3 kg for
      LY3298176 (vs -0.4 kg for placebo, -2.7 kg for dulaglutide). At 26 weeks, 14-71%
      of those treated with LY3298176 achieved the weight loss target of at least 5%
      (vs 22% with dulaglutide, 0% with placebo) and 6-39% achieved the weight loss
      target of at least 10% (vs 9% with dulaglutide, 0% with placebo). Changes in
      waist circumference ranged from -2.1 cm to -10.2 cm for LY3298176 (vs -1.3 cm for
      placebo, -2.5 cm for dulaglutide). Changes in total cholesterol ranged from 0.2
      mmol/L to -0.3 mmol/L for LY3298176 (vs 0.3 mmol/L for placebo, -0.2 mmol/L for
      dulaglutide). Changes in HDL or LDL cholesterol did not differ between the
      LY3298176 and placebo groups. Changes in triglyceride concentration ranged from 0
      mmol/L to -0.8 mmol/L for LY3298176 (vs 0.3 mmol/L for placebo, -0.3 mmol/L for
      dulaglutide). The 12-week outcomes were similar to those at 26 weeks for all
      secondary outcomes. 13 (4%) of 316 participants across the six treatment groups
      had 23 serious adverse events in total. Gastrointestinal events (nausea,
      diarrhoea, and vomiting) were the most common treatment-emergent adverse events.
      The incidence of gastrointestinal events was dose-related (23.1% for 1 mg
      LY3298176, 32.7% for 5 mg LY3298176, 51.0% for 10 mg LY3298176, and 66.0% for 15
      mg LY3298176, 42.6% for dulaglutide, 9.8% for placebo); most events were mild to
      moderate in intensity and transient. Decreased appetite was the second most
      common adverse event (3.8% for 1 mg LY3298176, 20.0% for 5 mg LY3298176, 25.5%
      for 10 mg LY3298176, 18.9% for 15 mg LY3298176, 5.6% for dulaglutide, 2.0% for
      placebo). There were no reports of severe hypoglycaemia. One patient in the
      placebo group died from lung adenocarcinoma stage IV, which was unrelated to
      study treatment. INTERPRETATION: The dual GIP and GLP-1 receptor agonist,
      LY3298176, showed significantly better efficacy with regard to glucose control
      and weight loss than did dulaglutide, with an acceptable safety and tolerability
      profile. Combined GIP and GLP-1 receptor stimulation might offer a new
      therapeutic option in the treatment of type 2 diabetes. FUNDING: Eli Lilly and
      Company.

PMID- 30293772
TI  - Lorcaserin: balancing efficacy with potential risks.

PMID- 30293773
TI  - Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth
      and Malignancy.
AB  - Dysregulation of extracellular matrix (ECM) deposition and cellular metabolism
      promotes tumor aggressiveness by sustaining the activity of key growth, invasion,
      and survival pathways. Yet mechanisms by which biophysical properties of ECM
      relate to metabolic processes and tumor progression remain undefined. In both
      cancer cells and carcinoma-associated fibroblasts (CAFs), we found that ECM
      stiffening mechanoactivates glycolysis and glutamine metabolism and thus
      coordinates non-essential amino acid flux within the tumor niche. Specifically,
      we demonstrate a metabolic crosstalk between CAF and cancer cells in which CAF
      derived aspartate sustains cancer cell proliferation, while cancer cell-derived
      glutamate balances the redox state of CAFs to promote ECM remodeling.
      Collectively, our findings link mechanical stimuli to dysregulated tumor
      metabolism and thereby highlight a new metabolic network within tumors in which
      diverse fuel sources are used to promote growth and aggressiveness. Furthermore,
      this study identifies potential metabolic drug targets for therapeutic
      development in cancer.

PMID- 30293774
TI  - Preserving Insulin Secretion in Diabetes by Inhibiting VDAC1 Overexpression and
      Surface Translocation in beta Cells.
AB  - Type 2 diabetes (T2D) develops after years of prediabetes during which high
      glucose (glucotoxicity) impairs insulin secretion. We report that the ATP
      conducting mitochondrial outer membrane voltage-dependent anion channel-1 (VDAC1)
      is upregulated in islets from T2D and non-diabetic organ donors under glucotoxic
      conditions. This is caused by a glucotoxicity-induced transcriptional program,
      triggered during years of prediabetes with suboptimal blood glucose control.
      Metformin counteracts VDAC1 induction. VDAC1 overexpression causes its
      mistargeting to the plasma membrane of the insulin-secreting beta cells with loss
      of the crucial metabolic coupling factor ATP. VDAC1 antibodies and inhibitors
      prevent ATP loss. Through direct inhibition of VDAC1 conductance, metformin, like
      specific VDAC1 inhibitors and antibodies, restores the impaired generation of ATP
      and glucose-stimulated insulin secretion in T2D islets. Treatment of db/db mice
      with VDAC1 inhibitor prevents hyperglycemia, and maintains normal glucose
      tolerance and physiological regulation of insulin secretion. Thus, beta cell
      function is preserved by targeting the novel diabetes executer protein VDAC1.

PMID- 30293775
TI  - Complement Component C3 Is Highly Expressed in Human Pancreatic Islets and
      Prevents beta Cell Death via ATG16L1 Interaction and Autophagy Regulation.
AB  - We show here that human pancreatic islets highly express C3, which is both
      secreted and present in the cytosol. Within isolated human islets, C3 expression
      correlates with type 2 diabetes (T2D) donor status, HbA1c, and inflammation.
      Islet C3 expression is also upregulated in several rodent diabetes models. C3
      interacts with ATG16L1, which is essential for autophagy. Autophagy relieves
      cellular stresses faced by beta cells during T2D and maintains cellular
      homeostasis. C3 knockout in clonal beta cells impaired autophagy and led to
      increased apoptosis after exposure of cells to palmitic acid and IAPP. In the
      absence of C3, autophagosomes do not undergo fusion with lysosomes. Thus, C3 may
      be upregulated in islets during T2D as a cytoprotective factor against beta cell
      dysfunction caused by impaired autophagy. Therefore, we revealed a previously
      undescribed intracellular function for C3, connecting the complement system
      directly to autophagy, with a broad potential importance in other diseases and
      cell types.

PMID- 30293777
TI  - Interventricular vessel of the heart and myocardial infarction-induced heart
      failure.

PMID- 30293776
TI  - The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune
      Tolerance and Trained Immunity.
AB  - Sepsis involves simultaneous hyperactivation of the immune system and immune
      paralysis, leading to both organ dysfunction and increased susceptibility to
      secondary infections. Acute activation of myeloid cells induced itaconate
      synthesis, which subsequently mediated innate immune tolerance in human
      monocytes. In contrast, induction of trained immunity by beta-glucan counteracted
      tolerance induced in a model of human endotoxemia by inhibiting the expression of
      immune-responsive gene 1 (IRG1), the enzyme that controls itaconate synthesis.
      beta-Glucan also increased the expression of succinate dehydrogenase (SDH),
      contributing to the integrity of the TCA cycle and leading to an enhanced innate
      immune response after secondary stimulation. The role of itaconate was further
      validated by IRG1 and SDH polymorphisms that modulate induction of tolerance and
      trained immunity in human monocytes. These data demonstrate the importance of the
      IRG1-itaconate-SDH axis in the development of immune tolerance and training and
      highlight the potential of beta-glucan-induced trained immunity to revert
      immunoparalysis.

PMID- 30293778
TI  - Associations between Race/Ethnicity, Uterine Fibroids, and Minimally Invasive
      Hysterectomy in the VA Healthcare System.
AB  - BACKGROUND: In the general population, Black and Latina women are less likely to
      undergo minimally invasive hysterectomy than White women, which may be related to
      racial/ethnic variation in fibroid prevalence and characteristics. Whether
      similar differences exist in the Department of Veterans Affairs Healthcare System
      (VA) is unknown. METHODS: Using VA clinical and administrative data, we
      identified all women veterans undergoing hysterectomy for benign indications in
      fiscal years 2012-2014. We identified hysterectomy route (laparoscopic
      with/without robot-assist, vaginal, abdominal) by International Classification of
      Diseases, 9th edition, codes. We used multinomial logistic regression to estimate
      associations of race/ethnicity with hysterectomy route and tested whether
      associations varied by fibroid diagnosis using an interaction term. Models
      adjusted for age, income, body mass index, gynecologic diagnoses, medical
      comorbidities, whether procedure was performed or paid for by VA, geographic
      region, and fiscal year. RESULTS: Among 2,744 identified hysterectomies, 53% were
      abdominal, 29% laparoscopic, and 18% vaginal. In multinomial models,
      racial/ethnic differences were present among veterans with but not without
      fibroid diagnoses (p value for interaction < .001). Among veterans with fibroids,
      Black veterans were less likely than White veterans to have minimally invasive
      hysterectomy (laparoscopic vs. abdominal relative risk ratio [RRR], 0.52; 95% CI,
      0.38-0.72; vaginal vs. abdominal RRR, 0.58; 95% CI, 0.43-0.73). Latina veterans
      were as likely as White veterans to have laparoscopic as abdominal hysterectomy
      (RRR, 1.34; 95% CI, 0.87-2.07) and less likely to have vaginal than abdominal
      hysterectomy (RRR, 0.32; 95% CI, 0.15-0.69). CONCLUSIONS: Receipt of minimally
      invasive hysterectomy among women veterans with fibroids varied by
      race/ethnicity. Further investigation of the underlying mechanisms and potential
      interventions to increase minimally invasive hysterectomy among minority women
      veterans is needed.

PMID- 30293779
TI  - Validation of a Holographic Display for Quantification of Mitral Annular Dynamics
      by Three-Dimensional Echocardiography.
AB  - BACKGROUND: Three-dimensional (3D) echocardiography with multiplanar
      reconstruction (MPR) is used clinically to quantify the mitral annulus. MPR
      images are, however, presented on a two-dimensional screen, calling into question
      their accuracy. An alternative to MPR is an autostereoscopic holographic display
      that enables in-depth visualization of 3D echocardiographic data without the need
      for special glasses. The aim of this study was to validate an autostereoscopic
      display using sonomicrometry as a gold standard. METHODS: In 11 anesthetized open
      chest pigs, sonomicrometric crystals were placed along the mitral annulus and
      near the left ventricular apex. High-fidelity catheters measured left atrial and
      ventricular pressures. Adjustments of pre- and afterload were done by
      constriction of the inferior vena cava and the ascending aorta, respectively.
      Three-dimensional epicardial echocardiography was obtained from an apical view
      and converted to the autostereoscopic display. A 3D virtual semitransparent
      annular surface (VSAS) was generated to measure commissure width (CW), septal
      lateral length, area of the mitral annular surface, nonplanarity angle, and the
      annular height-to-commissure width ratio in mid-systole and late diastole.
      RESULTS: Mitral annular measurements from the 3D VSAS derived from the 3D
      echocardiographic images and autostereoscopic display correlated well with
      sonomicrometry over a range of loading conditions: CW length (r = 0.98, P <
      .00001), septal-lateral length (r = 0.98, P < .00001), annular surface area (r =
      0.93, P < .001), nonplanarity angle (r = 0.87, P < .001), and annular height-to
      commissure width ratio (r = 0.85, P < .01). The 3D VSAS showed better agreement
      with the sonomicrometric measurements compared with MPR. CONCLUSIONS: Mitral
      annular measurements using 3D VSAS correlate well with sonomicrometry over a
      range of loading conditions and may represent a powerful tool for noninvasive
      quantification of mitral annular dynamics.

PMID- 30293782
TI  - Genetic Modulation of RNA Splicing with a CRISPR-Guided Cytidine Deaminase.
AB  - RNA splicing is a critical mechanism by which to modify transcriptome, and its
      dysregulation is the underlying cause of many human diseases. It remains
      challenging, however, to genetically modulate a splicing event in its native
      context. Here, we demonstrate that a CRISPR-guided cytidine deaminase (i.e.,
      targeted-AID mediated mutagenesis [TAM]) can efficiently modulate various forms
      of mRNA splicing. By converting invariant guanines to adenines at either 5' or 3'
      splice sites (SS), TAM induces exon skipping, activation of alternative SS,
      switching between mutually exclusive exons, or targeted intron retention.
      Conversely, TAM promotes downstream exon inclusion by mutating cytidines into
      thymines at the polypyrimidine tract. Applying this approach, we genetically
      restored the open reading frame and dystrophin function of a mutant DMD gene in
      patient-derived induced pluripotent stem cells (iPSCs). Thus, the CRISPR-guided
      cytidine deaminase provides a versatile genetic platform to modulate RNA splicing
      and to correct mutations associated with aberrant splicing in human diseases.

PMID- 30293781
TI  - Regulation of the Hippo Pathway by Phosphatidic Acid-Mediated Lipid-Protein
      Interaction.
AB  - The Hippo pathway plays a crucial role in organ size control and tumor
      suppression, but its precise regulation is not fully understood. In this study,
      we discovered that phosphatidic acid (PA)-related lipid signaling is a key
      regulator of the Hippo pathway. Supplementing PA in various Hippo-activating
      conditions activates YAP. This PA-related lipid signaling is involved in Rho
      mediated YAP activation. Mechanistically, PA directly interacts with Hippo
      components LATS and NF2 to disrupt LATS-MOB1 complex formation and NF2-mediated
      LATS membrane translocation and activation, respectively. Inhibition of
      phospholipase D (PLD)-dependent PA production suppresses YAP oncogenic
      activities. PLD1 is highly expressed in breast cancer and positively correlates
      with YAP activation, suggesting their pathological relevance in breast cancer
      development. Taken together, our study not only reveals a role of PLD-PA lipid
      signaling in regulating the Hippo pathway but also indicates that the PLD-PA-YAP
      axis is a potential therapeutic target for cancer treatment.

PMID- 30293780
TI  - Genomic Copy-Number Loss Is Rescued by Self-Limiting Production of DNA Circles.
AB  - Copy-number changes generate phenotypic variability in health and disease.
      Whether organisms protect against copy-number changes is largely unknown. Here,
      we show that Saccharomyces cerevisiae monitors the copy number of its ribosomal
      DNA (rDNA) and rapidly responds to copy-number loss with the clonal amplification
      of extrachromosomal rDNA circles (ERCs) from chromosomal repeats. ERC formation
      is replicative, separable from repeat loss, and reaches a dynamic steady state
      that responds to the addition of exogenous rDNA copies. ERC levels are also
      modulated by RNAPI activity and diet, suggesting that rDNA copy number is
      calibrated against the cellular demand for rRNA. Last, we show that ERCs reinsert
      into the genome in a dosage-dependent manner, indicating that they provide a
      reservoir for ultimately increasing rDNA array length. Our results reveal a DNA
      based mechanism for rapidly restoring copy number in response to catastrophic
      gene loss that shares fundamental features with unscheduled copy-number
      amplifications in cancer cells.

PMID- 30293784
TI  - The Proto-oncogene c-Kit Inhibits Tumor Growth by Behaving as a Dependence
      Receptor.
AB  - c-Kit is a classic proto-oncogene either mutated or upregulated in cancer cells,
      and this leads to its constitutive kinase activation and, thus, to uncontrolled
      proliferation. Although the pro-oncogenic role of c-Kit is of no doubt, some
      observations do not fit well with c-Kit solely as a tumor-promoting moiety. We
      show here that c-Kit actively triggers cell death in various cancer cell lines
      unless engaged by its ligand stem cell factor (SCF). This pro-death activity is
      enhanced when the kinase activation of c-Kit is silenced and is due to c-Kit
      intracellular cleavage by caspase-like protease at D816. Moreover, in vivo,
      overexpression of a c-Kit kinase-dead mutant inhibits tumor growth, and this
      intrinsic c-Kit tumor-suppressive activity is dependent on the D816 cleavage.
      Thus, c-Kit acts both as a proto-oncogene via its kinase activity and as a tumor
      suppressor via its dependence receptor activity.

PMID- 30293783
TI  - ZNF598 Is a Quality Control Sensor of Collided Ribosomes.
AB  - Aberrantly slow translation elicits quality control pathways initiated by the
      ubiquitin ligase ZNF598. How ZNF598 discriminates physiologic from pathologic
      translation complexes and ubiquitinates stalled ribosomes selectively is unclear.
      Here, we find that the minimal unit engaged by ZNF598 is the collided di
      ribosome, a molecular species that arises when a trailing ribosome encounters a
      slower leading ribosome. The collided di-ribosome structure reveals an extensive
      40S-40S interface in which the ubiquitination targets of ZNF598 reside. The
      paucity of 60S interactions allows for different ribosome rotation states,
      explaining why ZNF598 recognition is indifferent to how the leading ribosome has
      stalled. The use of ribosome collisions as a proxy for stalling allows the degree
      of tolerable slowdown to be tuned by the initiation rate on that mRNA; hence, the
      threshold for triggering quality control is substrate specific. These findings
      illustrate how higher-order ribosome architecture can be exploited by cellular
      factors to monitor translation status.

PMID- 30293787
TI  - Worsening alopecia in an elderly woman.

PMID- 30293786
TI  - Genome-wide Identification of Structure-Forming Repeats as Principal Sites of
      Fork Collapse upon ATR Inhibition.
AB  - DNA polymerase stalling activates the ATR checkpoint kinase, which in turn
      suppresses fork collapse and breakage. Herein, we describe use of ATR inhibition
      (ATRi) as a means to identify genomic sites of problematic DNA replication in
      murine and human cells. Over 500 high-resolution ATR-dependent sites were
      ascertained using two distinct methods: replication protein A (RPA)-chromatin
      immunoprecipitation (ChIP) and breaks identified by TdT labeling (BrITL). The
      genomic feature most strongly associated with ATR dependence was repetitive DNA
      that exhibited high structure-forming potential. Repeats most reliant on ATR for
      stability included structure-forming microsatellites, inverted retroelement
      repeats, and quasi-palindromic AT-rich repeats. Notably, these distinct
      categories of repeats differed in the structures they formed and their ability to
      stimulate RPA accumulation and breakage, implying that the causes and character
      of replication fork collapse under ATR inhibition can vary in a DNA-structure
      specific manner. Collectively, these studies identify key sources of endogenous
      replication stress that rely on ATR for stability.

PMID- 30293788
TI  - Bilateral hand edema: simply nothing or nothing simple?

PMID- 30293789
TI  - An unusual cause of intracranial hemorrhage.

PMID- 30293771
TI  - Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight
      and obese patients (CAMELLIA-TIMI 61): a randomised, placebo-controlled trial.
AB  - BACKGROUND: There is a direct relationship between bodyweight and risk of
      diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses
      appetite, has been shown to facilitate sustained weight loss in obese or
      overweight patients. We aimed to evaluate the long-term effects of lorcaserin on
      diabetes prevention and remission. METHODS: In this randomised, double-blind,
      placebo-controlled trial done in eight countries, we recruited overweight or
      obese patients (body-mass index >=27 kg/m2) with or at high risk for
      atherosclerotic vascular disease. Eligible patients were aged 40 years or older;
      patients at high risk for atherosclerotic vascular disease had to be aged 50
      years or older with diabetes and at least one other risk factor. Patients were
      randomly assigned to receive either lorcaserin (10 mg twice daily) or matching
      placebo. Additionally, all patients had access to a standardised weight
      management programme based on lifestyle modification. The prespecified primary
      metabolic efficacy endpoint of time to incident diabetes was assessed in patients
      with prediabetes at baseline. The prespecified secondary outcomes for efficacy
      were incident diabetes in all patients without diabetes, achievement of
      normoglycaemia in patients with prediabetes, and change in glycated haemoglobin
      (HbA1c) in patients with diabetes. Hypoglycaemia was a prespecified safety
      outcome. Analysis was by intention to treat, using Cox proportional hazard models
      for time-to-event analyses. This trial is registered with ClinicalTrials.gov,
      number NCT02019264. FINDINGS: Between Feb 7, 2014, and Nov 20, 2015, 12 000
      patients were randomly assigned to lorcaserin or placebo (6000 patients in each
      group) and followed up for a median of 3.3 years (IQR 3.0-3.5). At baseline, 6816
      patients (56.8%) had diabetes, 3991 (33.3%) prediabetes, and 1193 (9.9%)
      normoglycaemia. At 1 year, patients treated with lorcaserin had a net weight loss
      beyond placebo of 2.6 kg (95% CI 2.3-2.9) for those with diabetes, 2.8 kg (2.5
      3.2) for those with prediabetes, and 3.3 kg (2.6-4.0) for those with
      normoglycaemia (p<0.0001 for all analyses). Lorcaserin reduced the risk of
      incident diabetes by 19% in patients with prediabetes (172 [8.5%] of 2015 vs 204
      [10.3%] of 1976; hazard ratio 0.81, 95% CI 0.66-0.99; p=0.038) and by 23% in
      patients without diabetes (174 [6.7%] of 2615 vs 215 [8.4%] of 2569; 0.77, 0.63
      0.94; p=0.012). Lorcaserin resulted in a non-significant increase in the rate of
      achievement of normoglycaemia in patients with prediabetes (185 [9.2%] vs 151
      [7.6%]; 1.20, 0.97-1.49; p=0.093). In patients with diabetes, lorcaserin resulted
      in a reduction of 0.33% (95% CI 0.29-0.38; p<0.0001) in HbA1c compared with
      placebo at 1 year from a mean baseline of 53 mmol/mol (7.0%). In patients with
      diabetes at baseline, severe hypoglycaemia with serious complications was rare,
      but more common with lorcaserin (12 [0.4%] vs four [0.1%] events; p=0.054).
      INTERPRETATION: Lorcaserin decreases risk for incident diabetes, induces
      remission of hyperglycaemia, and reduces the risk of microvascular complications
      in obese and overweight patients, supporting the role of lorcaserin as an adjunct
      to lifestyle modification for chronic management of weight and metabolic health.
      FUNDING: Eisai.

PMID- 30293791
TI  - Lomustine in older patients with acute myeloid leukaemia.

PMID- 30293790
TI  - Brigatinib versus crizotinib for ALK-positive NSCLC.

PMID- 30293785
TI  - The Chromatin Reader ZMYND8 Regulates Igh Enhancers to Promote Immunoglobulin
      Class Switch Recombination.
AB  - Class switch recombination (CSR) is a DNA recombination reaction that diversifies
      the effector component of antibody responses. CSR is initiated by activation
      induced cytidine deaminase (AID), which targets transcriptionally active
      immunoglobulin heavy chain (Igh) switch donor and acceptor DNA. The 3' Igh super
      enhancer, 3' regulatory region (3'RR), is essential for acceptor region
      transcription, but how this function is regulated is unknown. Here, we identify
      the chromatin reader ZMYND8 as an essential regulator of the 3'RR. In B cells,
      ZMYND8 binds promoters and super-enhancers, including the Igh enhancers. ZMYND8
      controls the 3'RR activity by modulating the enhancer transcriptional status. In
      its absence, there is increased 3'RR polymerase loading and decreased acceptor
      region transcription and CSR. In addition to CSR, ZMYND8 deficiency impairs
      somatic hypermutation (SHM) of Igh, which is also dependent on the 3'RR. Thus,
      ZMYND8 controls Igh diversification in mature B lymphocytes by regulating the
      activity of the 3' Igh super-enhancer.

PMID- 30293792
TI  - Nurses' Knowledge, Attitudes, and Barriers Toward Pain Management Among
      Postoperative Patients in Jordan.
AB  - PURPOSE: The purpose of this study was to measure nurses' knowledge, attitudes,
      and barriers regarding pain management (PM) of postoperative patients in Jordan.
      DESIGN: A descriptive survey research design was used. METHODS: This descriptive
      study adopted a modified version of the "Knowledge and Attitudes Survey Regarding
      Pain" tool, administered to 120 nurses working in surgical wards. FINDINGS:
      Nurses had inadequate knowledge of PM, with a mean knowledge score of 63.9%.
      Knowledge of PM and attitudes toward PM were associated positively with the age
      of the participant (P = .001), years of experience in the surgical area (P =
      .026), and academic degree of participants (P = .026). CONCLUSIONS: Surgical
      nurses in this study had low knowledge levels and poor attitudes regarding PM in
      postoperative patients. Unless identified barriers to PM are seriously addressed,
      this vital aspect of holistic care will continue to be marginalized.

PMID- 30293793
TI  - Impact of diabetes on coronary artery plaque volume by coronary CT angiography
      and subsequent adverse cardiac events.
AB  - BACKGROUND: To investigate the impact of diabetes on coronary artery total plaque
      volume (TPV) and adverse events in long-term follow-up. METHODS: One-hundred-and
      eight diabetic patients were matched to 324 non-diabetic patients, with respect
      to age, sex, body-mass index, hypertension, smoking habits, LDL and HDL
      cholesterol, family history for CAD as well as aspirin and statin medication. In
      all patients, TPV was quantified from coronary CT angiographies (CTA) using
      dedicated software. All-cause mortality, acute coronary syndrome and late
      revascularisation (>90 days) served as combined endpoint. RESULTS: Patients were
      followed for 5.6 years. The endpoint occurred in 18 (16.7%) diabetic and 26
      (8.0%) non-diabetic patients (odds ratio 2.3, p = 0.03). Diabetic patients had
      significantly higher TPV than non-diabetic patients (55.1 mm3 [IQR: 6.2 and 220.4
      mm3] vs. 24.9 mm3 [IQR: 0 and 166.7 mm3], p = 0.02). A TPV threshold of 110.5 mm3
      provided good separation of diabetic and non-diabetic patients at higher and
      lower risk for adverse events. Noteworthy, diabetic and non-diabetic patients
      with a TPV<110.5 mm3 had comparable outcome (hazard ratio: 1.3, p = 0.59), while
      diabetic patients with TPV>110.5 mm3 had significantly higher incidence of
      adverse events (hazard ratio 2.3, p = 0.03) compared to non-diabetic patients
      with TPV>110.5 mm3. There was incremental prognostic value in diabetic and non
      diabetic patients over the Framingham Risk Score (Integrated Discrimination
      Improvement: 0.052 and 0.012, p for both <0.05). CONCLUSION: Diabetes is
      associated with significantly higher TPV, which is independent of other CAD risk
      factors. Quantification of TPV improves the identification of diabetic patients
      at higher risk for future adverse events.

PMID- 30293794
TI  - Design and synthesis of cell-permeable fluorescent nitrilotriacetic acid
      derivatives.
AB  - Fluorescence labeling of the target molecules using a small molecule-based probe
      is superior than a method using genetically expressed green fluorescence protein
      (GFP) in terms of convenience in its preparation and functionalization.
      Fluorophore-nitrilotriacetic acid (NTA) conjugates with several ester protecting
      groups were synthesized and evaluated for their cell membrane permeability by
      fluorescence microscopy analysis. One of the derivatives, acetoxymethyl (AM)
      protected NTA conjugate is hydrolyzed, resulting in intracellular accumulation,
      thus providing localized fluorescence intensity in cells. This modification is
      expected as an effective method for converting a non-cell membrane permeable NTA
      BODIPY conjugates to a cell membrane permeable derivatives.

PMID- 30293796
TI  - Discovery and anti-inflammatory evaluation of benzothiazepinones (BTZs) as novel
      non-ATP competitive inhibitors of glycogen synthase kinase-3beta (GSK-3beta).
AB  - Glycogen synthase kinase-3beta (GSK-3beta) has been identified to promote
      inflammation and its inhibitors have also been proven to treat some inflammatory
      mediated diseases in animal models. Non-ATP competitive inhibitors inherently
      have better therapeutical value due to their higher specificity than ATP
      competitive ones. In this paper, we designed and synthesized a series of new BTZ
      derivatives as non-ATP competitive GSK-3beta inhibitors. Kinetic analysis
      revealed two typical compounds 6j and 3j showed the different non-ATP competitive
      mechanism of substrate competition or allosteric modulation to GSK-3beta,
      respectively. As expected, the two compounds showed good specificity in a panel
      test of 16 protein kinases, even to the closest enzymes, like CDK-1/cyclin B and
      CK-II. The in vivo results proved that both compounds can greatly attenuate the
      LPS-induced acute lung injury (ALI) and diminish inflammation response in mice by
      inhibiting the mRNA expression of IL-1beta and IL-6. Western blot analysis
      demonstrated that they negatively regulated GSK-3beta, and the mechanism of the
      observed beneficial effects of the inhibitors may involve both the increased
      phosphorylation of the Ser9 residue on GSK-3beta and protein expression of
      Sirtuin 1 (SIRT1). The results support that such novel BTZ compounds have a
      protective role in LPS-induced ALI, and might be attractive candidates for
      further development of inflammation pharmacotherapy, which greatly thanks to
      their inherently high selectivities by the non-ATP competitive mode of action.
      Finally, we proposed suggesting binding modes by Docking study to well explain
      the impacts of compounds on the target site.

PMID- 30293795
TI  - Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and
      molecular docking study of indole-N-acylhydrazone derivatives.
AB  - The objective of this work was to obtain and evaluate anti-inflammatory in vitro,
      in vivo and in silico potential of novel indole-N-acylhydrazone derivatives. In
      total, 10 new compounds (3a-j) were synthesized in satisfactory yields, through a
      condensation reaction in a single synthesis step. In the lymphoproliferation
      assay, using mice splenocytes, 3a and 3b showed inhibition of lymphocyte
      proliferation of 62.7% (+/-3.5) and 50.7% (+/-2), respectively, while
      dexamethasone presented an inhibition of 74.6% (+/-2.4). Moreover, compound 3b
      induced higher Th2 cytokines production in mice splenocytes cultures. The results
      for COX inhibition assays showed that compound 3b is a selective COX-2 inhibitor,
      but with less potency when compared to celecoxib, and compound 3a not presented
      selectivity towards COX-2. The molecular docking results suggest compounds 3a and
      3b interact with the active site of COX-2 in similar conformations, but not with
      the active site of COX-1, and this may be the main reason to the COX-2
      selectivity of compound 3b. In vivo carrageenan-induced paw edema assays were
      adopted for the confirmation of the anti-inflammatory activity. Compound 3b
      showed better results in suppressing edema at all tested concentrations and was
      able to induce an edema inhibition of 100% after 5 h of carrageenan injection at
      the 30 mg kg-1 dosage, corroborating with the COX inhibition and
      lymphoproliferation results. I addition to our experimental results, in silico
      analysis suggest that compounds 3a and 3b present a well-balanced profile between
      pharmacodynamics and pharmacokinetics. Thus, our preliminary results revealed the
      potentiality of a new COX-2 selective derivative in the modulation of the
      inflammatory process.

PMID- 30293797
TI  - Design, synthesis, and systematic evaluation of 4-arylpiperazine- and 4
      benzylpiperidine napthyl ethers as inhibitors of monoamine neurotransmitters
      reuptake.
AB  - Two series of 4-arylpiperazine- and 4-benzylpiperidine naphthyl ethers were
      designed based on structure-activity relationship (SAR) and docking model of
      reported monoamine neurotransmitters reuptake inhibitors. The compounds were
      synthesized in 3-simple steps and their biological activities were evaluated.
      Several compounds were proven to be potent inhibitors of serotonin and
      norepinephrine reuptake. Computer docking was performed to study the interaction
      of the most potent compound 35 with human serotonin transporter. The results of
      the analyses suggest that 4-arylpiperazine- and 4-benzylpiperidine naphthyl
      ethers might be promising antidepressants worthy of further studies.

PMID- 30293798
TI  - [Evaluation of the quality of long-term anticoagulation therapy with antivitamin
      K in atrial fibrillation].
AB  - AIM: To assess the quality of long-term anticoagulation therapy with antivitamin
      K in patients with atrial fibrillation by measuring the TTR and to determine the
      factors associated with a good TTR. PATIENTS AND METHODS: This is an
      observational study conducted over a period of three years (from January 2013
      until December 2015) in the outpatient clinic of cardiology of Farhat Hached
      hospital of Sousse, Tunisia. Pre-established individual plugs were used for data
      collection. The data analysis was performed using the SPSS Software, version 20.
      RESULTS: Overall, 200 patients were eligible. Half of the patients did not know
      the risks of AVK and 29.1% were unaware of their interest. The average TTR was
      57.3+/-18.2%. Good control of anticoagulation was obtained in 24.5% of patients.
      Those with a>=70% were more autonomous, observant, of urban origin, living in
      Sousse and Kairouan, with good knowledge about AVK and having a small left
      atrium. The factors associated negatively with TTR were hypertension, diabetes,
      old AF, hematological diseases, high number of medications taken daily and the
      presence of mitral insufficiency, mitral valve replacement, a tricuspid
      insufficiency or a tricuspid plasty. CONCLUSION: The quality of AVK
      anticoagulation in AF patients is insufficient. Improving this indicator would
      reduce the morbidity and mortality associated with AVK treatment.

PMID- 30293799
TI  - Incidence and risk factors of peripheral venous catheter-related adverse events
      in cardiology department of a Tunisian university hospital: A prospective
      observational study.
AB  - AIM: The purpose of our study was to determine the incidence and risk factors of
      Peripheral Venous Catheter-Related Adverse Events (PVCAEs) in a cardiology
      department of a university hospital. PATIENTS AND METHODS: We carried out a
      prospective observational study from Mars 2017 to May 2017 in the cardiology
      department of the University Hospital of Farhat Hached in Sousse, Tunisia. During
      this period, we actively followed-up all inserted PVCs (every 12hours) from
      insertion up to 48hours after removal. Regression analyses were applied and
      significance limits were set at P<0.05. RESULTS: Data were analysed for 210 PVCs
      (794 PVC-days) in 148 patients. The incidence of PVCAEs was 33.33% with density
      of incidence of 8.81/1000 PVC-days. PVCAEs were mainly pain (50%) and mechanical
      events (31.42%). Infections accounted for 11.42%. The most frequent mechanical
      PVCAEs, was haematoma (15.71%). Multivariate analysis revealed as independent
      factors for the occurrence of PVCAEs: the hydro electrolytic nature of the
      injected product (OR=13.42, P<10-3), the medicinal nature of the injected product
      (OR=5.08, P=0.003), bad cutaneous state (OR=8.08, P=0.003), admission during
      nightshift (OR=3.76; P=0.014) and advanced age (OR=1.04, P=0.042). CONCLUSION:
      Multicenter studies would be very useful to better analyze risk factors
      associated with PVCAEs.

PMID- 30293800
TI  - Differentiation of focal organising pneumonia and peripheral adenocarcinoma in
      solid lung lesions using thin-section CT-based radiomics.
AB  - AIM: To evaluate the predictive role of radiomics based on computed tomography
      (CT) in discriminating focal organising pneumonia (FOP) from peripheral lung
      adenocarcinoma (LA). MATERIALS AND METHODS: Institutional research board approval
      was obtained for this retrospective study. One hundred and seventeen patients
      with FOP and 109 patients with LA who underwent thin-section CT from January 2011
      to August 2017 were reviewed systematically and analysed. The clinical and
      radiological features were established as model A and multi-feature-based
      radiomics as model B. The diagnostic performance of model A, model B, and model
      A+B were evaluated and compared via receiver operating characteristic (ROC) curve
      analysis and logistic regression analysis. RESULTS: Sex, symptoms, necrosis, and
      the halo sign were identified as independent predictors of LA. The area under the
      ROC curve (Az value), accuracy, sensitivity, and specificity of model A were
      0.839, 75.7%, 82.6%, and 69.2% respectively. Model B showed significantly higher
      accuracy than model A (83.6% versus 75.7%, p=0.032). The top four best-performing
      features, WavEnLH_s-3, WavEnHH_s-3, Teta3, and Volume, performed as independent
      factors for discriminating LA. Regression analysis indicated that model B had
      superior model fit than model A with Akaike information criterion (AIC) values of
      73.6% versus 59.1%, respectively. Combining model A with model B is useful in
      achieving better diagnostic performance in discriminating FOP from LA: the Az
      value, accuracy, sensitivity, and specificity were 0.956, 87.6%, 85.3%, and 89.7%
      respectively. CONCLUSIONS: Radiomics based on CT exhibited better diagnostic
      accuracy and model fit than clinical and radiological features in discriminating
      FOP from LA. Combination of both achieved better diagnostic performance.

PMID- 30293801
TI  - Total virtual workflow in CAD-CAM bony reconstruction with a single step free
      fibular graft and immediate dental implants.
AB  - The Surgical reconstruction of defects of the face is challenging. Local and
      regional flaps have an important part to play, but large defects of bone and soft
      tissue are a greater problem. Microvascular tissue transfer has become the
      standard for such patients, and preoperative planning of bony reconstructions is
      now common. To use these preplanning tools best the implants should be placed in
      the prosthetically ideal place, and the bone positioned to surround the implants 
      that is, truly backward planning of the position of the bone. The buccolingual
      angulation and the actual position of the implants during operation can be
      difficult to verify. Using commonly available software and 3-dimensional printing
      solutions, therefore, we have constructed an algorithm to optimise the position
      of these implants during the operation, and to get their position as close to the
      planned outcome as possible. This algorithm is adaptable to any implant system
      and is potentially possible in any implant or preplanning software unit.

PMID- 30293802
TI  - Transoral vertical ramus osteotomy fixed with Kirschner pins.
AB  - Transoral vertical ramus osteotomy (VRO) has been condemned because the condyle
      has the potential to sag, and because it needs lengthy maxillomandibular
      fixation. We have therefore introduced a simple method of fixation, and examined
      its effectiveness and complications. After the osteotomy, the proximal and distal
      segments are trimmed to adapt to each other. Four Kirschner (K) pins 0.9mm in
      diameter are inserted percutaneously from the proximal to the distal segment
      while the condyle is positioned in the glenoid fossa. This is followed by a brief
      period of maxillomandibular fixation. We have reviewed the records of 95 patients
      who had unilateral or bilateral vertical ramus osteotomy fixed with K pins, after
      which the mean (SD) period of fixation was 19 (11) days. Fixation failed in two
      patients because excursion of the jaw was either too heavy or too early. The
      fixations were redone. All other fixations remained stable, including the 20 dual
      jaw procedures in which VRO preceded maxillary osteotomy. The mean (SD) maximal
      mouth opening at final follow-up was 44 (7) mm, and in only one patient was it
      less than 30mm. Numbness of the lip or chin developed in seven patients, five of
      whom had other anterior mandibular procedures. Four patients had discomfort on
      palpation of the site of the pins, and one required removal. The new method was
      effective, and resulted in few complications within its limitations.

PMID- 30293803
TI  - Distribution of metastatic regional lymph nodes in squamous cell carcinoma of the
      oral commissure and its implications for treatment in the neck.

PMID- 30293805
TI  - Risk factors for bleeding after dental extractions in patients over 60 years of
      age who are taking antiplatelet drugs.
AB  - The aim of this retrospective, single-centre study was to identify the risk
      factors for bleeding after dental extractions in patients aged over 60 who were
      being treated with antiplatelet drugs. A total of 338 patients who fulfilled the
      inclusion criteria were enrolled, and their personal and clinical details, and
      complications with bleeding after extraction, were retrieved and recorded. There
      were 182 men and 156 women (mean (SD) age 72 (8) years). A total of 469 teeth
      were extracted, with a mean (SD) of 1.4 (0.6) teeth/patient. Seventy-seven
      patients (23%) developed mild, and 55 (16%) severe, bleeding postoperatively. No
      patient developed a major cardiovascular or cerebrovascular event. We calculated
      the significance of the association of different variables with the occurrence of
      postoperative haemorrhage using a multivariate stepwise logistic regression
      model. The presence of three or more coexisting conditions, a complicated tooth
      extraction, and the use of two antiplatelet drugs were independent risk factors,
      while discontinuation of antiplatelet treatment four or more days before the
      tooth was extracted was a protective factor. This suggests that clinicians should
      assess the thrombotic risk associated with the interruption of antiplatelet drugs
      as well as the risk of bleeding for each patient before dental extraction. Strong
      and effective measures for haemostasis may be preferred over blind
      discontinuation of antiplatelet drugs. This study is registered in the Chinese
      Clinical Trial Registry (No. ChiCTR1800014355).

PMID- 30293804
TI  - Accuracy of a CAD/CAM surgical template for mandibular distraction: a preliminary
      study.
AB  - We have assessed the accuracy and clinical validation of virtual planning using a
      surgical template in 16 patients with hemifacial microsomia being treated by
      mandibular distraction osteogenesis. Virtual planning and simulation were first
      done on three-dimensional models. Distraction was simulated on the virtual model
      and the new morphology of the mandible was previewed. Both the position and
      direction of the distractor were calculated to achieve the optimal morphology.
      The templates were designed based on the virtual planning, and manufactured using
      a 3-dimensional printing technique. The template was designed to assist the
      surgeon to make the osteotomy and predrill the screw-holes to guide the
      distractor into position. The outcome was evaluated by comparing planned with
      postoperative outcomes. The osteotomy was made and the distractor implanted
      successfully under the guidance of the template in all patients. The linear and
      angular differences for the distractor were measured and reported using the root
      mean square deviation. There was no difficulty in using the templates. The
      largest linear root mean square deviation between the planned and the
      postoperative distractors was 0.93mm in the anteroposterior direction, and the
      largest in the horizontal plane was 4.64 degrees . We suggest that the
      preoperative plan can be transferred accurately to a patient using the template.

PMID- 30293806
TI  - Outcome of salvage procedures for recurrent oral and oropharyngeal cancer.
AB  - Despite advances in the primary treatment of oral and oropharyngeal cancer, many
      patients develop local or regional recurrence, or both, and when radiotherapy has
      already been used, operation provides the best chance of salvage for these
      patients. We have looked at the outcomes of salvage procedures in a single unit,
      including improved survival, morbidity, and treatment-related quality of life.
      Patients treated with salvage procedures were identified from a prospectively
      completed database. Overall and disease-free survival were analysed using Kaplan
      Meier curves and logrank tests. Functional, social, and emotional outcomes were
      assessed using the University of Washington Quality of Life Questionnaires.
      Twenty-nine patients were identified, of whom 24 had free flap reconstructions,
      and their estimated mean overall survival was 25 months (95% CI 20.4 to 29.2).
      Disease-free survival was significantly worse in patients with stage IV
      recurrences or in whom resection margins were close or invaded. Permanent
      gastrostomy was required in 15/29 patients, and four/29 needed a permanent
      tracheostomy. Answers to questionnaires showed that a large proportion of
      patients had considerable problems with speech, chewing, swallowing, and
      appearance. The decision on whether to treat recurrent head and neck cancer is a
      balance between improving survival and poor functional outcomes. The extent of
      disease and whether clear surgical margins can be achieved should be considered
      when treatment is recommended.

PMID- 30293807
TI  - Impact of reconstructive microsurgery on patients with cancer of the head and
      neck: a prospective study of quality of life, particularly in older patients.
AB  - Treatment of cancer of the head and neck often requires extended resection and
      major reconstructive surgery, both of which can have great functional and
      emotional impact. It is fundamental to evaluate the outcome with respect not only
      to the clinical aspects but also to the quality of life (QoL) perceived by the
      patients. In the light of the reported increasing incidence of oral cancer in
      older patients, we decided to see if there was an association between QoL and
      age. Between June 2015 and December 2016 we submitted the Italian version of the
      36-item Short Form Health Survey (SF-36) to 30 patients (mean (range) age 65.5
      (23-87) years) who had had resection and microsurgical reconstruction at the
      Ospedale Maggiore Policlinico of Milan. The questionnaires were completed before
      operation, and 12 months afterwards, and clinical and personal data were also
      collected. From the results of SF-36 we obtained the Short Form 12 (SF-12),
      Physical Health Composite Score (PCS), and Mental Health Composite Score (MCS)
      and looked at how age influences the variation in QoL scores. The variation
      between SF-36 and SF-12 results (preoperatively and postoperatively) did not seem
      to correlate with age. Our study confirmed that reconstructive microsurgery can
      be realistically proposed to older as well as younger patients because, according
      to the QoL index, older patients are able to manage (and therefore take advantage
      of) this complex surgical technique.

PMID- 30293808
TI  - Impact of a Direct Bedding Initiative on Left Without Being Seen Rates.
AB  - BACKGROUND: Left without being seen (LWBS) rates have become a key metric of
      emergency department (ED) flow, and high rates have been associated with poor
      patient outcomes, especially at busy urban, academic hospitals. OBJECTIVE: To
      assess a triage intervention's impact on LWBS rates among Emergency Severity
      Index (ESI) level 2 patients especially at risk for adverse outcomes. METHODS: We
      conducted a retrospective review at an urban academic center of LWBS rates prior
      to and after a "direct bedding" intervention, which directed patients triaged to
      ESI level 2 to be immediately placed in any available ED area, including those
      typically reserved for lower-acuity complaints. Our primary analysis employs an
      adjusted difference-in-difference-in-difference (DDD) approach using controls
      from the previous year and a nearby affiliate community hospital that did not
      participate in the intervention. RESULTS: Mean daily patient volume increased
      from 275 to 298 arrivals after the intervention. In the primary DDD analysis,
      odds of LWBS were lower after the intervention (adjusted odds ratio [OR] 0.56,
      95% confidence interval [CI] 0.45-0.70, p < 0.001). LWBS was higher in the
      unadjusted analysis (unadjusted OR 1.39, 95% CI 1.31-1.49, p < 0.001), but still
      lower among ESI 1 or 2 patients targeted by the intervention (unadjusted OR 0.56,
      95% CI 0.43-0.74, p < 0.001). CONCLUSIONS: "Direct bedding" of ESI 2 patients may
      expedite care for the sickest patients, reducing potential harm to patients who
      might otherwise LWBS, without compromising care for patients triaged to less
      acute ESI levels.

PMID- 30293809
TI  - Genomic Clues for Crop-Weed Interactions and Evolution.
AB  - Agronomically critical weeds that have evolved alongside crop species are
      characterized by rapid adaptation and invasiveness, which can result in an
      enormous reduction in annual crop yield worldwide. We discuss here recent genome
      based research studies on agricultural weeds and crop-weed interactions that
      reveal several major evolutionary innovations such as de-domestication,
      interactions mediated by allelochemical secondary metabolites, and parasitic
      genetic elements that play crucial roles in enhancing weed invasiveness in
      agricultural settings. We believe that these key studies will guide future
      research into the evolution of crop-weed interactions, and further the
      development of practical applications in agricultural weed control and crop
      breeding.

PMID- 30293811
TI  - Molecular Basis for Membrane Recruitment by the PX and C2 Domains of Class II
      Phosphoinositide 3-Kinase-C2alpha.
AB  - Phosphorylation of phosphoinositides by the class II phosphatidylinositol 3
      kinase (PI3K) PI3K-C2alpha is essential for many processes, including
      neuroexocytosis and formation of clathrin-coated vesicles. A defining feature of
      the class II PI3Ks is a C-terminal module composed of phox-homology (PX) and C2
      membrane interacting domains; however, the mechanisms that control their specific
      cellular localization remain poorly understood. Here we report the crystal
      structure of the C2 domain of PI3K-C2alpha in complex with the phosphoinositide
      head-group mimic inositol hexaphosphate, revealing two distinct pockets for
      membrane binding. The C2 domain preferentially binds to phosphatidylinositol 4,5
      bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate, and low-resolution
      structures of the combined PX-C2 module by small-angle X-ray scattering reveal a
      compact conformation in which cooperative lipid binding by each domain binding
      can occur. Finally, we demonstrate an unexpected role for calcium in perturbing
      the membrane interactions of the PX-C2 module, which we speculate may be
      important for regulating the activity of PI3K-C2alpha.

PMID- 30293810
TI  - Hydrogen-Deuterium Exchange Coupled to Top- and Middle-Down Mass Spectrometry
      Reveals Histone Tail Dynamics before and after Nucleosome Assembly.
AB  - Until recently, a major limitation of hydrogen-deuterium exchange mass
      spectrometry (HDX-MS) was that resolution of deuterium localization was limited
      to the length of the peptide generated during proteolysis. However, electron
      transfer dissociation (ETD) has been shown to preserve deuterium label in the gas
      phase, enabling better resolution. To date, this technology remains mostly
      limited to small, already well-characterized proteins. Here, we optimize, expand,
      and adapt HDX-MS tandem MS (MS/MS) capabilities to accommodate histone and
      nucleosomal complexes on top-down HDX-MS/MS and middle-down HDX-MS/MS platforms
      and demonstrate that near site-specific resolution of deuterium localization can
      be obtained with high reproducibility. We are able to study histone tail dynamics
      in unprecedented detail, which have evaded analysis by traditional structural
      biology techniques for decades, revealing important insights into chromatin
      biology. Together, the results of these studies highlight the versatility,
      reliability, and reproducibility of ETD-based HDX-MS/MS methodology to
      interrogate large protein and protein/DNA complexes.

PMID- 30293813
TI  - Keys to optimize the operating room efficiency.
AB  - Healthcare is in constant transformation. Health systems should focus on
      improving efficiency to meet a growing demand for high-quality, low-cost health
      care. The operating room is one of the biggest sources of revenue and one of the
      largest areas of expense. Therefore, operating room management is a critical key
      to success. The aim of this article is to analyze the current principles of
      organization, optimization and clinical management of the operating room and its
      impact on the quality and safety of care.

PMID- 30293812
TI  - Automatic Inference of Sequence from Low-Resolution Crystallographic Data.
AB  - At resolutions worse than 3.5 A, the electron density is weak or nonexistent at
      the locations of the side chains. Consequently, the assignment of the protein
      sequences to their correct positions along the backbone is a difficult problem.
      In this work, we propose a fully automated computational approach to assign
      sequence at low resolution. It is based on our surprising observation that
      standard reciprocal-space indicators, such as the initial unrefined R value, are
      sensitive enough to detect an erroneous sequence assignment of even a single
      backbone position. Our approach correctly determines the amino acid type for 15%,
      13%, and 9% of the backbone positions in crystallographic datasets with
      resolutions of 4.0 A, 4.5 A, and 5.0 A, respectively. We implement these findings
      in an application for threading a sequence onto a backbone structure. For the
      three resolution ranges, the application threads 83%, 81%, and 64% of the
      sequences exactly as in the deposited PDB structures.

PMID- 30293814
TI  - Connecting Chronically Ill, Uninsured Patients Who Use the Emergency Department
      as a Medical Home: A Process Improvement Project.
AB  - INTRODUCTION: The use of the emergency department by uninsured patients with
      chronic health problems may adversely affect those patients' health outcomes.
      Successful interventions have involved the use of patient navigators to connect
      the uninsured adult population with medical coverage and a medical home. The aim
      of this project was to use principles of patient navigation in a nurse-led
      process improvement intervention to connect uninsured patients to medical homes.
      METHOD: ED nurses were trained to refer uninsured patients with chronic health
      problems to care coordinators when they were discharged from emergency
      departments. The care coordinator was provided by the Health Care District, a
      community-funded medical department. Patients were therefore connected to
      community-funded medical homes. RESULTS: ED nurses improved their knowledge about
      the overuse of the emergency department and successfully referred uninsured
      patients who were discharged. The referred patients successfully made contact
      with members of the Health Care District by phone or by attending their
      appointments. CONCLUSION: The role of patient navigators is essential in the
      emergency department. They assist patients to navigate through the various health
      care resources available in their communities, which can help to reduce ED
      overuse.

PMID- 30293815
TI  - Antidepressant Induced Hallucinations, Rhabdomyolysis, and Hyperkalemia in the
      Geriatric Population: A Case Overview.

PMID- 30293816
TI  - Does a Provider in Triage and Rapid Medical Evaluation Help With Left Without
      Being Seen Rates and ED Crowding?
AB  - INTRODUCTION: Attempting to reduce ED crowding, the ED team at a rural academic
      medical center and specialty hospital implemented rapid medical evaluation (RME)
      with and without a provider in triage (PIT). The purpose of this performance
      improvement project was to explore how these interventions affected crowding
      metrics of door-to-disposition time, ED length of stay (LOS), and left without
      being seen (LWBS) rates for all patients. METHODS: Using a prospective 2-group
      design, the pre-RME population served as the historical control group, and
      postintervention groups included both RME with and without PIT. Group comparisons
      of crowding metrics included pre- and post-RME with and without PIT. RESULTS:
      There were no statistically significant differences in any of the crowding
      metrics for the emergency severity index (ESI) 3 groups pre- or post-RME.
      However, mean door-to-disposition times for the post-RME ESI 5 population were
      shorter compared with the pre-RME ESI 5 patients (2:59:23 vs. 2:00: 42; P =
      0.037). Analysis of the post-RME population with and without PIT did not
      demonstrate significant differences across ESI 3 or 5 groups. Comparisons of post
      RME data revealed a significant increase in ED LOS for all admitted patients
      regardless of their ESI (P = 0.023) and also door-to-disposition times for ESI
      level-4 patient groups, both with and without PIT (P = 0.022). IMPLICATIONS FOR
      PRACTICE: The findings support other studies demonstrating that RME can have
      positive impact on ED crowding metrics for some patients. Although PIT took
      longer for some patients, anecdotal findings revealed benefits related to direct
      discharges and admission occurring during the RME process.

PMID- 30293817
TI  - Identification of Novel Cdc7 Kinase Inhibitors as Anti-Cancer Agents that Target
      the Interaction with Dbf4 by the Fragment Complementation and Drug Repositioning
      Approach.
AB  - BACKGROUND: Cdc7-Dbf4 is a conserved serine/threonine kinase that plays an
      important role in initiation of DNA replication and DNA damage tolerance in
      eukaryotic cells. Cdc7 has been found overexpressed in human cancer cell lines
      and tumor tissues, and the knockdown of Cdc7 expression causes an p53-independent
      apoptosis, suggesting that Cdc7 is a target for cancer therapy. Only a handful
      Cdc7 kinase inhibitors have been reported. All Cdc7 kinase inhibitors, including
      PHA-767491, were identified and characterized as ATP-competitive inhibitors.
      Unfortunately, these ATP-competitive Cdc7 inhibitors have no good effect on
      clinical trial. METHODS: Here, we have developed a novel drug-screening platform
      to interrupt the interaction between Cdc7 and Dbf4 based on Renilla reniformis
      luciferase (Rluc)-linked protein-fragment complementation assay (Rluc-PCA). Using
      drug repositioning approach, we found several promising Cdc7 inhibitors for
      cancer therapy from a FDA-approved drug library. FINDINGS: Our data showed that
      dequalinium chloride and clofoctol we screened inhibit S phase progression,
      accumulation in G2/M phase, and Cdc7 kinase activity. In addition, in vivo mice
      animal study suggests that dequalinium chloride has a promising anti-tumor
      activity in oral cancer. Interestingly, we also found that dequalinium chloride
      and clofoctol sensitize the effect of platinum compounds and radiation due to
      synergistic effect. In conclusion, we identified non-ATP-competitive Cdc7 kinase
      inhibitors that not only blocks DNA synthesis at the beginning but also
      sensitizes cancer cells to DNA damage agents. INTERPRETATION: The inhibitors will
      be a promising anti-cancer agent and enhance the therapeutic effect of
      chemotherapy and radiation for current cancer therapy. FUND: This work was
      supported by grants from the Ministry of Science and Technology, Ministry of
      Health and Welfare, and National Health Research Institutes, Taiwan.

PMID- 30293819
TI  - The role of diffusion weighted imaging as supplement to dynamic contrast enhanced
      breast MRI: Can it help predict malignancy, histologic grade and recurrence?
AB  - RATIONALE AND OBJECTIVES: To evaluate the value of adding Diffusion Weighted
      Imaging (DWI) with Apparent Diffusion Coefficient (ADC) mapping to dynamic
      contrast enhanced (DCE-MRI) to distinguish benign from malignant pathology
      subtypes and tumor recurrence. METHOD AND MATERIALS: In this retrospective IRB
      approved study, 956 consecutive patients underwent bilateral breast MRI between
      1/2015 and 12/2015, with 156 BIRADS 4, 5, or 6 lesions detected in 111 patients.
      DWI imaging at B0, B100, B600, B1000 was performed with DCE-MRI. Values for
      diffusion and ADC images were recorded by two fellowship-trained breast
      radiologists. Mean ADC and signal intensity (SI) values were correlated with
      histology, tumor grade, hormone receptors (ER, PR, and HER-2)and Oncotype DX
      scores, when available. p <= 0.05 was considered significant. RESULTS: Of 156
      lesions, there were 59 (38%) benign lesions, 24 (15%) Ductal Carcinoma In-Situ,
      47 (30%) Invasive Ductal Carcinoma (IDC), 15 (10%) Invasive Lobular Carcinoma
      (ILC) and 2 (2%) Mucinous carcinoma (MC), five (5%) mixed IDC and ILC, and four
      (4%) other, including tubular and rare types of malignancy. Mean ADC values for
      malignancy were significantly lower than for benign lesions (1085 +/- 343 * 10-6
      vs 1481 +/- 276 * 10-6 mm2/s), which is highly predictive (area under curve =
      0.82). In addition, tumors with PR negativity and Oncotype score >=18
      (intermediate to high risk for recurrence) demonstrated significantly lower ADC
      values. SI at B100 and B600 was helpful in distinguishing benign versus IDC.
      There was no significant correlation between ADC values and tumor grade or
      ER/HER2 status. CONCLUSION: ADC value is important factor in distinguishing
      malignancy, differentiating tumors with higher Oncotype score, and PR negativity.
      Therefore, it can be used as an important tool to assist appropriate treatment
      selection.

PMID- 30293818
TI  - Long non-coding RNA LINC-01572:28 inhibits granulosa cell growth via a decrease
      in p27 (Kip1) degradation in patients with polycystic ovary syndrome.
AB  - BACKGROUND: Disordered folliculogenesis is a key feature of polycystic ovary
      syndrome (PCOS), but the underlying molecular mechanism remains unclear. METHODS:
      Long non-coding RNA (lncRNA) expression in luteinized granulosa cells (hLGCs)
      derived from women with and without PCOS were analyzed using microarray and qRT
      PCR. Immortalized human granulosa cell lines were cultured for proliferation
      assays after transfection with the LINC-01572:28 over-expression vector in the
      presence or absence of p27 siRNA. Protein expression analysis, rescue assays, and
      RNA immunoprecipitation (RIP) were used to confirm the LINC-01572:28 substrate.
      FINDINGS: LINC-01572:28 and p27 protein were elevated whereas proliferating cell
      nuclear antigen protein was decreased in the hLGCs of women with PCOS. LINC
      01572:28 expression was positively correlated with basal testosterone levels.
      Over-expression of LINC-01572:28 inhibited cell proliferation and impeded G1/S
      transition, which were partially reversed by siRNA-mediated p27 knockdown.
      INTERPRETATION: Our findings, therefore, suggest that LINC-01572:28 suppresses
      cell proliferation and cell cycle progression by reducing the degradation of p27
      protein via SKP2 binding.

PMID- 30293820
TI  - Small signal averaged transfer function model and controller design of modular
      solid state transformers.
AB  - The prime objective of this paper is to design and develop simple and efficient
      closed loop controllers independently for each of the conversion stages of a
      Modular Solid State Transformer (MSST) for low/medium voltage applications. The
      controller design is based on small signal averaged transfer function model using
      topology independent black box approach. Hence it can be universally adopted for
      any choice of topologies. The independently designed controllers enhance the
      modularity of the apparatus such that extension and reduction of ac/dc voltage
      and power levels are possible by addition and removal of modules as and when
      required. This paves way for easy maintenance and replacement of modules.
      Further, the cost and complexity in control is reduced to enable large scale
      market penetration of the apparatus. Time and frequency response plots are
      illustrated to validate the performance of the individual converters with the
      designed closed loop controllers. The simple control design adopted for MSST is
      shown to mitigate power quality issues to a greater extent possible. Simulation
      and experimental results are presented which substantiate the appropriateness of
      the small signal model and hence the controllers designed for the MSST.

PMID- 30293821
TI  - Oxytocin Transforms Firing Mode of CA2 Hippocampal Neurons.
AB  - Oxytocin is an important neuromodulator in the mammalian brain that increases
      information salience and circuit plasticity, but its signaling mechanisms and
      circuit effect are not fully understood. Here we report robust oxytocinergic
      modulation of intrinsic properties and circuit operations in hippocampal area
      CA2, a region of emerging importance for hippocampal function and social
      behavior. Upon oxytocin receptor activation, CA2 pyramidal cells depolarize and
      fire bursts of action potentials, a consequence of phospholipase C signaling to
      modify two separate voltage-dependent ionic processes. A reduction of potassium
      current carried by KCNQ-based M channels depolarizes the cell; protein kinase C
      activity attenuates spike rate of rise and overshoot, dampening after
      hyperpolarizations. These actions, in concert with activation of fast-spiking
      interneurons, promote repetitive firing and CA2 bursting; bursting then governs
      short-term plasticity of CA2 synaptic transmission onto CA1 and, thus, efficacy
      of information transfer in the hippocampal network.

PMID- 30293822
TI  - Ephaptic Coupling Promotes Synchronous Firing of Cerebellar Purkinje Cells.
AB  - Correlated neuronal activity at various timescales plays an important role in
      information transfer and processing. We find that in awake-behaving mice, an
      unexpectedly large fraction of neighboring Purkinje cells (PCs) exhibit sub
      millisecond synchrony. Correlated firing usually arises from chemical or
      electrical synapses, but, surprisingly, neither is required to generate PC
      synchrony. We therefore assessed ephaptic coupling, a mechanism in which neurons
      communicate via extracellular electrical signals. In the neocortex, ephaptic
      signals from many neurons summate to entrain spiking on slow timescales, but
      extracellular signals from individual cells are thought to be too small to
      synchronize firing. Here we find that a single PC generates sufficiently large
      extracellular potentials to open sodium channels in nearby PC axons. Rapid
      synchronization is made possible because ephaptic signals generated by PCs peak
      during the rising phase of action potentials. These findings show that ephaptic
      coupling contributes to the prevalent synchronization of nearby PCs.

PMID- 30293823
TI  - Neural Coding of Leg Proprioception in Drosophila.
AB  - Animals rely on an internal sense of body position and movement to effectively
      control motor behavior. This sense of proprioception is mediated by diverse
      populations of mechanosensory neurons distributed throughout the body. Here, we
      investigate neural coding of leg proprioception in Drosophila, using in vivo two
      photon calcium imaging of proprioceptive sensory neurons during controlled
      movements of the fly tibia. We found that the axons of leg proprioceptors are
      organized into distinct functional projections that contain topographic
      representations of specific kinematic features. Using subclass-specific genetic
      driver lines, we show that one group of axons encodes tibia position
      (flexion/extension), another encodes movement direction, and a third encodes
      bidirectional movement and vibration frequency. Overall, our findings reveal how
      proprioceptive stimuli from a single leg joint are encoded by a diverse
      population of sensory neurons, and provide a framework for understanding how
      proprioceptive feedback signals are used by motor circuits to coordinate the
      body.

PMID- 30293824
TI  - Effects of freeze-thaw on the biomechanical and structural properties of the rat
      Achilles tendon.
AB  - Rodent models are commonly used to investigate tendon healing, with the
      biomechanical and structural properties of the healed tendons being important
      outcome measures. Tendon storage for later testing becomes necessary when
      performing large experiments with multiple time-points. However, it is unclear
      whether freezing rodent tendons affects their material properties. Thus the aim
      of this study was to determine whether freezing rat Achilles tendons affects
      their biomechanical or structural properties. Tendons were frozen at either -20 
      degrees C or -80  degrees C directly after harvesting, or tested when freshly
      harvested. Groups of tendons were subjected to several freeze-thaw cycles (1, 2,
      and 5) within 3 months, or frozen for 9 months, after which the tendons were
      subjected to biomechanical testing. Additionally, fresh and thawed tendons were
      compared morphologically, histologically and by transmission electron microscopy.
      No major differences in biomechanical properties were found between fresh tendons
      and those frozen once or twice at -20  degrees C or -80  degrees C. However,
      deterioration of tendon properties was found for 5-cycle groups and both long
      term freezing groups; after 9 months of freezing at -80  degrees C the tear
      resistance of the tendon was reduced from 125.4 +/- 16.4N to 74.3 +/- 18.4N (p =
      0.0132). Moreover, tendons stored under these conditions showed major disruption
      of collagen fibrils when examined by transmission electron microscopy. When
      examined histologically, fresh samples exhibited the best cellularity and
      proteoglycan content of the enthesis. These properties were preserved better
      after freezing at -80  degrees C than after freezing at -20  degrees C, which
      resulted in markedly smaller chondrocytes and less proteoglycan content. Overall,
      the best preservation of histological integrity was seen with tendons frozen once
      at -80  degrees C. In conclusion, rat Achilles tendons can be frozen once or
      twice for short periods of time (up to 3 months) at -20  degrees C or -80 
      degrees C for later testing. However, freezing for 9 months at either -20 
      degrees C or -80  degrees C leads to deterioration of certain parameters.

PMID- 30293825
TI  - Evaluation of pulmonary artery stenosis in congenital heart disease patients
      using functional diagnostic parameters: An in vitro study.
AB  - Congenital pulmonary artery (PA) stenosis is often associated with abnormal PA
      hemodynamics including increased pressure drop (Deltap) and reduced asymmetric
      flow (Q), which may result in right ventricular dysfunction. We propose
      functional diagnostic parameters, pressure drop coefficient (CDP), energy loss
      (Eloss), and normalized energy loss (E-loss) to characterize pulmonary
      hemodynamics, and evaluate their efficacy in delineating stenosis severity using
      in vitro experiments. Subject-specific test sections including the main PA (MPA)
      bifurcating into left and right PAs (LPA, RPA) with a discrete LPA stenosis were
      manufactured from cross-sectional imaging and 3D printing. Three clinically
      relevant stenosis severities, 90% area stenosis (AS), 80% AS, and 70% AS, were
      evaluated at different cardiac outputs (COs). A benchtop flow loop simulating
      pulmonary hemodynamics was used to measure Q and Deltap within the test sections.
      The experimental Deltap-Q characteristics along with clinical data were used to
      obtain pathophysiologic conditions and compute the diagnostic parameters. The
      pathophysiologic QLPA decreased as the stenosis severity increased at a fixed CO.
      CDPLPA, Eloss,LPA (absolute), and E-loss,LPA (absolute) increased with an
      increase in LPA stenosis severity at a fixed CO. Importantly, CDPLPA and E
      loss,LPA had reduced variability with CO, and distinct values for each LPA
      stenosis severity. Under variable CO, a) CDPLPA values were 14.5-21.0 (70% AS),
      60.7- 2.2 (80% AS), >= 261.6 (90% AS), and b) E-loss,LPA values (in mJ per QLPA)
      were -501.9 to -1023.8 (70% AS), -1247.6 to -1773.0 (80% AS), -1934.5 (90% AS).
      Hence, CDPLPA and E-loss,LPA are expected to assess the true functional severity
      of PA stenosis.

PMID- 30293826
TI  - Assessment of ocular redness measurements obtained with keratograph 5M and
      correlation with subjective grading scales.
AB  - OBJECTIVE: To examine correlations between ocular redness scores provided by the
      Keratograph 5M and those determined using two image-based grading scales.
      METHODS: Observational prospective cross-sectional study. Two hundred and twenty
      six eyes of two hundred and twenty six participants (175 patients using anti
      glaucoma eye drops and 51 subjects untreated). All subjects were scored
      automatically using the keratograph 5M. These redness scores (RS) were then
      correlated with the gradings provided by the Efron and McMonnies/Chapman-Davies
      scale (MC-D) scales (two observers). RESULTS: Excellent reproducibility was
      observed for both the Efron (weighted K=0.897, 95% CI 0.823-0.904) and MC-D
      (weighted K=0.783, 95% CI 0.752-0.795) scales. Keratograph RS and the scores
      obtained with both Efron (Spearman's Rho=0.43, P<0.001) and MC-D (Spearman's
      Rho=0.48, P<0.001) scales were significantly correlated. RS for the bulbar and
      limbal - nasal and temporal quadrants also correlated moderately with the two
      subjective scales. Through Bland Altman analysis, poor agreement was detected
      between the objective and subjective methods: agreement values for the Efron
      scale or MC-D scale (matching scorers between observers) versus overall RS showed
      high biases (-15.58 and -22.05 respectively) and wide limits of agreement (LOA) (
      46.169 to 15.005 and -52.534 to 8.19 respectively). Lowest bias was observed
      between temporal limbal RS and Observer 2 Efron score (-0.04). CONCLUSIONS:
      Although it emerged as a reliable objective method, the keratograph 5M
      overestimated the scores compared with the subjective grading scales when used to
      grade the degree of ocular redness. Therefore, they should not be interchangeable
      methods.

PMID- 30293827
TI  - Thoracolumbar Osteomyelitis Secondary to Systemic Mycobacterium Chimaera
      Infection Status Post Aortic Valve Replacement.

PMID- 30293828
TI  - Regional Versus General Anesthesia for Carotid Endarterectomy: Do We Need Another
      Randomized Trial?

PMID- 30293830
TI  - Practice Patterns for the Use of Perioperative Transesophageal Echocardiography:
      A Practice not yet Made Perfect.

PMID- 30293829
TI  - Predictors of Short-term Outcomes Following Repair of Anomalous Origin of the
      Left Coronary Artery From the Pulmonary Artery in Chinese Children: A Case
      Control Study.
AB  - OBJECTIVE: To analyze the predictive factors associated with prolonged mechanical
      ventilation (PMV) and prolonged duration of inotropic support (PDIS) following
      anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      surgery with possible concomitant mitral valve procedure (MVP) in a relatively
      young population. DESIGN: A retrospective case-control study. SETTING: Fuwai
      hospital. PARTICIPANTS: Pediatric patients with ALCAPA surgery from July 2010 to
      October 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PMV was defined
      as a mechanical ventilation time >=48 hours and PDIS as a duration of inotropic
      support >=6 days. Univariate analysis, logistic regression analysis, and receiver
      operating characteristic curve analysis were used to identify independent
      predictors of PMV and PDIS. The independent predictors of PMV were found to be
      the left ventricular end-diastolic diameter z-score (LVEDDz), estimate of
      glomerular filtration rate (eGFR) and maximum vasoactive-inotropic score (VISm).
      The odds ratios and 95% confidence intervals for these predictors of PMV were the
      following: LVEDDz, 1.58 (1.19-2.09); eGFR, 0.96 (0.93-0.998); and VISm, 1.08
      (1.01-1.17). The predictor of PDIS was LVEDDz at 1.65 (1.26-2.15). One patient
      died during hospitalization, and there was no reoperation. Thirty-seven patients
      received concomitant MVP with no hospital mortality. At discharge, mitral
      regurgitation (MR) had improved in all patients with MR. Patients with PMV were
      associated with more acute kidney injury, PDIS, and longer ICU and hospital
      stays. CONCLUSIONS: In relatively young individuals who received ALCAPA surgery
      and possible concomitant MVP, short-term outcomes are favorable. Based on their
      experience bias, the authors recommend combining LVEDDz, eGFR, and VISm to
      predict PMV and applying LVEDDz for PDIS.

PMID- 30293831
TI  - Continuous Ropivacaine Infusion Offers No Benefit in Treating Postoperative Pain
      After Cardiac Surgery.
AB  - OBJECTIVE: One multimodal pain management method for reducing postoperative
      opioid need after cardiac surgery is to continuously infuse local anesthetic into
      a median sternotomy wound. Previous studies have shown contradictory results with
      this method; therefore, no consensus exists on its effectiveness. The authors
      tested the effectiveness of continuous 0.2% ropivacaine infusion into a
      sternotomy wound after cardiac surgery. DESIGN: Prospective, randomized, double
      blinded, placebo-controlled trial. SETTING: Single-institution, tertiary-level,
      university hospital. PARTICIPANTS: Total of 90 patients undergoing coronary
      artery bypass grafting or heart valve surgery. INTERVENTIONS: Patients were
      assigned randomly to receive 0.2% ropivacaine or placebo into a sternotomy wound
      for 48 hours postoperatively. Pain was controlled with standardized oxycodone
      boluses after surgery and patient-controlled analgesia oxycodone after
      extubation; total oxycodone consumption was recorded. Pain was assessed 3  times
      daily, at rest and during deep breathing, with the visual analogue scale.
      MEASUREMENTS AND MAIN RESULTS: Forty-seven patients were assigned to receive
      ropivacaine and 43 to receive placebo infusion. Cumulative oxycodone consumption
      was 97 +/- 27 mg with ropivacaine and 96 +/- 29 mg with placebo (p = 0.813). Pain
      scores were similar between groups, both at rest (p = 0.630) and during deep
      breathing (p = 0.793). Adverse event incidences and surgical wound infection
      rates were similar between groups. CONCLUSION: Continuous 0.2% ropivacaine
      infusions at the median sternotomy wound did not reduce postoperative pain or
      opioid consumption during the first 48 hours after cardiac surgery. This
      technique apparently was not beneficial for post-sternotomy pain treatment.

PMID- 30293832
TI  - Between a Rock and a Hard Place: Coagulation Management in Venoarterial
      Extracorporeal Membrane Oxygenation Patients.

PMID- 30293833
TI  - Comparison of the Efficacy of Ultrasound-Guided Serratus Anterior Plane Block,
      Pectoral Nerves II Block, and Intercostal Nerve Block for the Management of
      Postoperative Thoracotomy Pain After Pediatric Cardiac Surgery.
AB  - OBJECTIVE: The aim of this study was to compare the relative efficacy of
      ultrasound-guided serratus anterior plane block (SAPB), pectoral nerves (Pecs) II
      block, and intercostal nerve block (ICNB) for the management of post-thoracotomy
      pain in pediatric cardiac surgery. DESIGN: A prospective, randomized, single
      blind, comparative study. SETTING: Single-institution tertiary referral cardiac
      center. PARTICIPANTS: The study comprised 108 children with congenital heart
      disease requiring surgery through a thoracotomy. INTERVENTIONS: Children were
      allocated randomly to 1 of the 3 groups: SAPB, Pecs II, or ICNB. All participants
      received 3 mg/kg of 0.2% ropivacaine for ultrasound-guided block after induction
      of anesthesia. Postoperatively, intravenous paracetamol was used for multimodal
      and fentanyl was used for rescue analgesia. MEASUREMENTS AND MAIN RESULTS: A
      modified objective pain score (MOPS) was evaluated at 1, 2, 4, 6, 8, 10, and 12
      hourspost-extubation. The early mean MOPS at 1, 2, and 4 hourswas similar in the
      3 groups. The late mean MOPS was significantly lower in the SAPB group compared
      with that of the ICNB group (p < 0.001). The Pecs II group also had a lower MOPS
      compared with the ICNB group at 6, 8, and 10 hours(p < 0.001), but the MOPS was
      comparable at hour 12 (p = 0.301). The requirement for rescue fentanyl was
      significantly higher in ICNB group in contrast to the SAPB and Pecs II groups.
      CONCLUSION: SAPB and Pecs II fascial plane blocks are equally efficacious in post
      thoracotomy pain management compared with ICNB, but they have the additional
      benefit of being longer lasting and are as easily performed as the traditional
      ICNB.

PMID- 30293834
TI  - Decannulation of a Ventricular Assist Device.

PMID- 30293835
TI  - [An atypical outcome of sporadic Creutzfeldt-Jakob disease in an elderly
      patient].

PMID- 30293836
TI  - Permanent prostate brachytherapy monotherapy with I-125 for low- and intermediate
      risk prostate cancer: Outcomes in 974 patients.
AB  - PURPOSE: To report outcomes of patients undergoing low-dose-rate (LDR)
      brachytherapy and investigate factors associated with biochemical failure and
      survival. METHODS: Consecutive patients undergoing LDR with I-125 at our
      institution between 1998 through 2013 for primary intact prostate cancer were
      examined. Those with low- and intermediate-risk disease receiving LDR with a
      minimum of 2 years followup and at least one post-LDR prostate-specific antigen
      (PSA) were included. RESULTS: About 974 patients satisfied inclusion criteria.
      With median followup of 72 months, biochemical failure occurred in 45 patients.
      Freedom from biochemical failure as defined by the Phoenix criterion was 96% and
      88% at 5 and 10 years, worse for intermediate risk as compared with low risk,
      with 10-year freedom from biochemical failure of 76% versus 92% (hazard ratio
      [HR] = 3.7, p < 0.001), respectively. On multivariable analysis, increased
      prebiopsy PSA, Gleason 4 + 3, and no androgen deprivation therapy were associated
      with biochemical failure. Gleason 4 + 3 was the factor most strongly associated
      with biochemical failure (HR = 7.01, p < 0.001). No examined factors were
      associated with local failure. Gleason 4 + 3 disease increased the likelihood of
      distant metastasis (HR = 12.4, p = 0.003) and prostate cancer-specific death (HR
      = 13.2, p < 0.001). No difference in outcomes between patients with Gleason 3 + 3
      versus 3 + 4 was observed. CONCLUSIONS: LDR brachytherapy provided excellent
      outcomes in this large series of patients treated for localized organ-confined
      prostate cancer. Local recurrence at 10 years was low at 2.1%. Primary Gleason 4
      + 3, higher pretreatment PSA, and no receipt of androgen deprivation therapy were
      the only factors associated with biochemical failure. Primary Gleason 4 disease
      was also predictive of distant metastases and decreased prostate cancer-specific
      survival.

PMID- 30293837
TI  - RSK-MASTL Pathway Delays Meiotic Exit in Mouse Zygotes to Ensure Paternal
      Chromosome Stability.
AB  - During vertebrate fertilization, sperm chromatin remodeling occurs concomitantly
      with maternal chromosome segregation at anaphase II, leading to simultaneous
      formation of two pronuclei. In mammals, these processes take much longer than in
      other vertebrates. Here, we explore the molecular basis and physiological
      importance of this mammalian-specific temporal regulation using mouse oocytes. We
      demonstrate the involvement of protein phosphatase in temporal regulation. Early
      onset of pronuclear formation causes paternal-biased abnormalities in pronuclear
      morphology and chromosome segregation at the first mitosis. After oocyte
      activation, CDK1-MASTL-ENSA, a protein phosphatase 2A-suppressive pathway,
      remains active despite the absence of cyclin B and contributes to delayed
      pronuclear formation. Sustained activation of MASTL involves ribosomal S6 kinase
      (RSK)-mediated phosphorylation of Thr297, which is conserved only among mammalian
      MASTLs. Our findings reveal the role of RSK in mouse oocytes, showing that the
      RSK-MASTL pathway allows mammalian-specific prolonged meiotic exit and ensures
      the faithful conversion from sperm to paternal pronuclei.

PMID- 30293840
TI  - Human SEIPIN Binds Anionic Phospholipids.
AB  - The biogenesis of lipid droplets (LDs) and the development of adipocytes are two
      key aspects of mammalian fat storage. SEIPIN, an integral membrane protein of the
      endoplasmic reticulum (ER), plays a critical role in both LD formation and
      adipogenesis. The molecular function of SEIPIN, however, has yet to be
      elucidated. Here, we report the cryogenic electron microscopy structure of human
      SEIPIN at 3.8 A resolution. SEIPIN exists as an undecamer, and this
      oligomerization state is critical for its physiological function. The
      evolutionarily conserved lumenal domain of SEIPIN forms an eight-stranded beta
      sandwich fold. Both full-length SEIPIN and its lumenal domain can bind anionic
      phospholipids including phosphatidic acid. Our results suggest that SEIPIN forms
      a scaffold that helps maintain phospholipid homeostasis and surface tension of
      the ER.

PMID- 30293841
TI  - Implementing an evidence-based psychological intervention for suicidal thoughts
      and behaviors on an inpatient unit: Process, challenges, and initial findings.
AB  - OBJECTIVE: Barriers to implementing evidence-based psychological treatments for
      suicidal thoughts and behaviors in busy hospital settings exist. Transdiagnostic
      interventions may serve to facilitate training in evidence-based treatment and
      more efficiently treat individuals with multiple psychiatric comorbidities. We
      describe the rationale for, process of, and initial data from implementing the
      Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) on an
      inpatient unit for adults with suicidal thoughts and behaviors and affective
      disorders. METHOD: We analyzed clinical intake and outcome data from a subsample
      of patients admitted during the six months before and six months after UP
      implementation (n = 133 and n = 61, respectively), and available acceptability
      and fidelity data from the month following UP implementation. RESULTS: Patients
      improved significantly over the course of inpatient treatment before and after UP
      implementation. Effects for depression, suicidal ideation, anxiety, and emotion
      regulation were similar before and after UP implementation. Patients generally
      reported high acceptability of the UP and clinician fidelity to the protocol was
      variable during the month following UP implementation. CONCLUSIONS: The UP may be
      a promising evidence-based intervention for inpatient settings that treat
      individuals with suicidal thoughts and behaviors. Well-controlled, randomized
      trials are needed to determine efficacy, particularly regarding suicidal behavior
      after discharge.

PMID- 30293838
TI  - Inheritance of CENP-A Nucleosomes during DNA Replication Requires HJURP.
AB  - Centromeric chromatin defines the site of kinetochore formation and ensures
      faithful chromosome segregation. Centromeric identity is epigenetically specified
      by the incorporation of CENP-A nucleosomes. DNA replication presents a challenge
      for inheritance of centromeric identity because nucleosomes are removed to allow
      for replication fork progression. Despite this challenge, CENP-A nucleosomes are
      stably retained through S phase. We used BioID to identify proteins transiently
      associated with CENP-A during DNA replication. We found that during S phase,
      HJURP transiently associates with centromeres and binds to pre-existing CENP-A,
      suggesting a distinct role for HJURP in CENP-A retention. We demonstrate that
      HJURP is required for centromeric nucleosome inheritance during S phase. HJURP co
      purifies with the MCM2-7 helicase complex and, together with the MCM2 subunit,
      binds CENP-A simultaneously. Therefore, pre-existing CENP-A nucleosomes require
      an S phase function of the HJURP chaperone and interaction with MCM2 to ensure
      faithful inheritance of centromere identity through DNA replication.

PMID- 30293839
TI  - A Membrane Transporter Is Required for Steroid Hormone Uptake in Drosophila.
AB  - Steroid hormones are a group of lipophilic hormones that are believed to enter
      cells by simple diffusion to regulate diverse physiological processes through
      intracellular nuclear receptors. Here, we challenge this model in Drosophila by
      demonstrating that Ecdysone Importer (EcI), a membrane transporter identified
      from two independent genetic screens, is involved in cellular uptake of the
      steroid hormone ecdysone. EcI encodes an organic anion transporting polypeptide
      of the evolutionarily conserved solute carrier organic anion superfamily. In
      vivo, EcI loss of function causes phenotypes indistinguishable from ecdysone- or
      ecdysone receptor (EcR)-deficient animals, and EcI knockdown inhibits cellular
      uptake of ecdysone. Furthermore, EcI regulates ecdysone signaling in a cell
      autonomous manner and is both necessary and sufficient for inducing ecdysone
      dependent gene expression in culture cells expressing EcR. Altogether, our
      results challenge the simple diffusion model for cellular uptake of ecdysone and
      may have wide implications for basic and medical aspects of steroid hormone
      studies.

PMID- 30293842
TI  - Emergency Department patients with suicide risk: Differences in care by acute
      alcohol use.
AB  - OBJECTIVE: To compare Emergency Department (ED) care of suicidal patients with
      and without documented acute alcohol use. METHODS: Retrospective chart review of
      randomly sampled patient visits (n = 800; January 2014 to December 2015) at an
      urban ED with universal screening for suicide risk. Eligible visits were by
      adults (18+ years) who screened positive for suicide risk at the ED visit (i.e.,
      suicidal ideation in past two weeks or suicide attempt in past six months).
      Analyses compared those with and without documentation of acute alcohol use.
      RESULTS: Among these patients with suicide risk, 19% had documented acute alcohol
      use (versus 43% with no use and 38% without documentation); individuals with
      acute alcohol use were more often male and aged 35-59 years. Overall, 62% were
      evaluated by a mental health professional in the ED. Individuals with acute
      alcohol use were significantly less likely (vs those without use) to be evaluated
      by a mental health professional in the ED (odds ratio 0.49, 95%CI 0.28-0.87)
      after adjustment for age, recent suicide ideation, current suicide plan, self
      harm as a chief complaint, contact with family, and ED disposition. CONCLUSIONS:
      Although alcohol use can increase suicide risk, ED patients with acute use appear
      to receive less thorough suicide risk assessments.

PMID- 30293843
TI  - Advanced airway management in out of hospital cardiac arrest: A systematic review
      and meta-analysis.
AB  - OBJECTIVES: To assess the difference in survival and neurological outcomes
      between endotracheal tube (ETT) intubation and supraglottic airway (SGA) devices
      used during out-of-hospital cardiac arrest (OHCA). METHODS: A systematic search
      of five databases was performed by two independent reviewers until September
      2018. Included studies reported on (1) OHCA or cardiopulmonary resuscitation, and
      (2) endotracheal intubation versus supraglottic airway device intubation.
      Exclusion criteria (1) stimulation studies, (2) selectively included/excluded
      patients, (3) in-hospital cardiac arrest. Odds Ratios (OR) with random effect
      modelling was used. Primary outcomes: (1) return of spontaneous circulation
      (ROSC), (2) survival to hospital admission, (3) survival to hospital discharge,
      (4) discharge with a neurologically intact state. RESULTS: Twenty-nine studies (n
      = 539,146) showed that overall, ETT use resulted in a heterogeneous, but
      significant increase in ROSC (OR = 1.44; 95%CI = 1.27 to 1.63; I2 = 91%; p <
      0.00001) and survival to admission (OR = 1.36; 95%CI = 1.12 to 1.66; I2 = 91%; p
      = 0.002). There was no significant difference in survival to discharge or
      neurological outcome (p > 0.0125). On sensitivity analysis of RCTs, there was no
      significant difference in ROSC, survival to admission, survival to discharge or
      neurological outcome (p > 0.0125). On analysis of automated chest compression,
      without heterogeneity, ETT provided a significant increase in ROSC (OR = 1.55;
      95%CI = 1.20 to 2.00; I2 = 0%; p = 0.0009) and survival to admission (OR = 2.16;
      95%CI = 1.54 to 3.02; I2 = 0%; p < 0.00001). CONCLUSIONS: The overall
      heterogeneous benefit in survival with ETT was not replicated in the low risk
      RCTs, with no significant difference in survival or neurological outcome. In the
      presence of automated chest compressions, ETT intubation may result in survival
      benefits.

PMID- 30293844
TI  - Emergency physicians and nurses can provide percutaneous cardiopulmonary support
      in emergency departments.

PMID- 30293845
TI  - On-pump beating CABG concomitant with bilateral living-donor lobar lung
      transplantation.

PMID- 30293846
TI  - Response to "High fatigue frequency in narcolepsy type 1 and type 2 in a
      Brazilian Sleep Center".

PMID- 30293847
TI  - Benzodiazepines and Z-drugs may cause prolonged cognitive issues in young adults 
      are hypnotics not only a geriatric dilemma?

PMID- 30293848
TI  - Symposium review: Embryo survival-A genomic perspective of the other side of
      fertility.
AB  - The majority of embryonic loss in cattle occurs within the first 3 to 4 wk of
      pregnancy, and there are currently no accurate predictors of pregnancy outcome.
      Existing embryo quality assessment methods include morphological evaluation and
      embryo biopsy. These methods are not accurate and carry some health risks to the
      developing embryo, respectively. Therefore, there is need to identify noninvasive
      biomarkers such as microRNA that can predict embryo quality and pregnancy
      outcome. Furthermore, researchers need a better understanding of the dynamic
      interaction between the mother and the embryo. The transcriptome of the uterus
      shows plasticity that depends on the embryo type so that the expression level of
      some genes for in vivo embryos would be different from that of in vitro-produced
      embryos. Similarly, the embryonic transcriptome and epigenome change in response
      to different environmental factors such as stress, diet, disease, and
      physiological status of the mother. This embryo-mother crosstalk could be better
      understood by investigating the molecular signaling that occurs at different
      stages of embryonic development. Although transcriptomics is a useful tool to
      assess the roles of genes and pathways in embryo quality and maternal
      receptivity, it does not provide the exact functions of these genes, and it shows
      correlation rather than causality. Therefore, an in-depth functional genomic
      analysis is needed for better understanding of the molecular mechanisms
      controlling embryo development. In this review, we discuss recent genomic
      technologies such as RNA interference, gapmer technology, and genome editing
      techniques used in humans and livestock to elucidate the molecular mechanisms of
      genes affecting embryo development.

PMID- 30293849
TI  - [Is cancer a factor or a marker of cardiovascular risk in women?]
AB  - Cardiovascular diseases and cancers are the 2 main causes of mortality in
      industrialized countries. Cancer and cardiovascular disease share molecular and
      pathophysiological mechanisms involved in both cardiovascular disease and cancer
      development. Some prescribed therapies for primary or secondary prevention of
      cardiovascular disease (statin, aspirin) may have effects on the cancer plan.
      Physical activity would be particularly beneficial in reducing the risk of
      colorectal cancer, breast and endometrial cancer in women. The control of risk
      factors is associated with a reduction in the incidence of cancers.

PMID- 30293850
TI  - [Place of natriuretic peptides in the early diagnosis of heart failure in
      community medicine].
AB  - Diagnosis of heart failure is too late. Symptoms of heart failure are non
      specific. Brain natriuretic peptides allow the diagnosis of heart failure in
      pauci-symptomatic patients, with a threshold of 35pg/mL for BNP and 125pg/mL for
      NT-proBNP. Left ventricular dysfunction, either diastolic or systolic, remains
      asymptomatic for a long time. In diabetic and/or hypertensive patients,
      natriuretic peptides, can be used to diagnose asymptomatic left ventricular
      dysfunction, with a threshold of 125pg/mL NT-proBNP. Treatment blocking the renin
      angiotensin-aldosterone system in diabetic patients with NT-proBNP levels of
      125pg/mL can prevent onset of heart failure. Screening of subjects at risk of
      heart failure (diabetics, hypertensive) is possible thanks to natriuretic
      peptides.

PMID- 30293851
TI  - [Arterial hypertension with multiple organ damage: A new entity?]
AB  - Hypertensive emergency. Stable incidence for several decades or even increasing
      (under diagnosed). Early and specific management improves prognosis. Absence of
      eye damage or lack of access to fundus should not delay or prevent the diagnosis.
      Multi Organ Damage Hypertension: new definition for an old entity: unusual,
      sudden and persistent blood pressure rise without threshold and ocular
      involvement or involvement of at least 3 target organs among brain, heart, kidney
      or endothelial disease.

PMID- 30293853
TI  - Development of a novel resection and cutting guide for mandibular reconstruction
      using free fibula flap.
AB  - INTRODUCTION: The authors developed a semi-standardised resection and cutting
      guide for mandibular reconstruction with free fibula flap based on data of
      mandible sizes and angles. METHODS: After analyzing the angles and lengths of
      mandibular angles and segments on computer tomography, a partly-adjustable
      resection guide for the mandible and cutting guide for the fibula were designed.
      RESULTS: After testing and optimizing the guides on plastic models and cadavers,
      the guides were successfully used for mandible resection and reconstruction with
      free fibula flap in 8 patients with segmental mandibulectomy. Application of the
      cutting and resection guides and functional results like occlusion and aesthetic
      appearence were satisfactory in all cases. CONCLUSIONS: The developed semi
      standardised device is a helpful instrument for facilitating reconstruction of
      segmental mandibular defects with free fibula flaps. No extensive preoperative
      preparation and 3D printing is necessary which can avoid additional costs for
      virtual planning. Especially for lower budget health systems this can be an
      alternative to virtual planning.

PMID- 30293852
TI  - Selective Elimination of Culture-Adapted Human Embryonic Stem Cells with BH3
      Mimetics.
AB  - The selective survival advantage of culture-adapted human embryonic stem cells
      (hESCs) is a serious safety concern for their clinical application. With a set of
      hESCs with various passage numbers, we observed that a subpopulation of hESCs at
      late passage numbers was highly resistant to various cell death stimuli, such as
      YM155, a survivin inhibitor. Transcriptome analysis from YM155-sensitive (YM155S)
      and YM155-resistant (YM155R) hESCs demonstrated that BCL2L1 was highly expressed
      in YM155R hESCs. By matching the gene signature of YM155R hESCs with the Cancer
      Therapeutics Response Portal dataset, BH3 mimetics were predicted to selectively
      ablate these cells. Indeed, short-course treatment with a sub-optimal dose of BH3
      mimetics induced the spontaneous death of YM155R, but not YM155S hESCs by
      disrupting the mitochondrial membrane potential. YM155S hESCs remained
      pluripotent following BH3 mimetics treatment. Therefore, the use of BH3 mimetics
      is a promising strategy to specifically eliminate hESCs with a selective survival
      advantage.

PMID- 30293854
TI  - Community-level social capital and cognitive decline after a natural disaster: A
      natural experiment from the 2011 Great East Japan Earthquake and Tsunami.
AB  - We examined prospectively whether community-level social capital can mitigate the
      adverse effects of natural disaster on cognitive decline in the aftermath of the
      2011 Great East Japan Earthquake and Tsunami. The baseline for our natural
      experimental study was established seven months before the disaster in a survey
      of older community-dwelling adults who lived in Iwanuma City, Japan, located 80
      km west of the epicenter. Two and a half years after the disaster, we conducted a
      follow-up survey of survivors to gather information about their personal
      experiences during the disaster (n = 3560; 82.1% follow-up rate). Our primary
      outcome was the level of cognitive disability (measured on an 8-level scale)
      assessed within people's homes. Factor analysis established two subscales of
      community social capital: a cognitive dimension (perceptions of community social
      cohesion) and a structural dimension (informal socializing and social
      participation). The prevalence of cognitive decline at follow-up (11.5%) was
      three times higher than at baseline (4.2%). Our multiple membership multilevel
      model indicated that pre-versus post-disaster increases in community-level
      informal socializing and social participation were associated with lower risk of
      cognitive decline (coefficient = -0.12, 95% confidence interval: -0.20 to -0.04).
      In addition, social capital mitigated the risk of cognitive decline due to
      housing damage (interaction effect coefficient = -0.07, 95% confidence interval: 
      0.14 to -0.01). Community-level informal socializing and social participation
      buffers the impact of housing damage on cognitive decline in the aftermath of
      natural disaster. Relocating residents together with other community members may
      help to preserve community social capital and improve the cognitive resilience of
      older survivors.

PMID- 30293855
TI  - Hygge but harmful? Wood-burning stoves under scrutiny.

PMID- 30293856
TI  - Corrections.

PMID- 30293857
TI  - Pro-resolving lipid mediators: Agents of anti-ageing?
AB  - Inflammation is an essential response to injury and its timely and adequate
      resolution permits tissue repair and avoidance of chronic inflammation. Ageing is
      associated with increased inflammation, sub-optimal resolution and these act as
      drivers for a number of ageing-associated pathologies. We describe the role
      played by specialised proresolving lipid mediators (SPMs) in the resolution of
      inflammation and how insufficient levels of these mediators, or compromised
      responsiveness may play a role in the pathogenesis of many ageing-associated
      pathologies, e.g. Alzheimer's Disease, atherosclerosis, obesity, diabetes and
      kidney disease. Detailed examination of the resolution phase of inflammation
      highlights the potential to harness these lipid mediators and or mimetics of
      their bioactions, in particular, their synthetic analogues to promote effective
      resolution of inflammation, without compromising the host immune system.

PMID- 30293858
TI  - Outcomes of revision arthroplasty for shoulder periprosthetic joint infection: a
      three-stage revision protocol.
AB  - BACKGROUND: This study evaluated outcomes after treatment of shoulder
      periprosthetic joint infection (PJI) with a 3-stage revision protocol consisting
      of (1) debridement, explantation, and cement spacer placement, followed by
      parenteral antibiotics; (2) open biopsy and debridement; and (3) reimplantation
      if cultures were negative. We hypothesized this protocol would eradicate
      persistent infection while producing excellent functional and subjective
      outcomes, and there would be no difference in these parameters for patients with
      shoulder PJI compared with patients with revision for aseptic indications.
      METHODS: We retrospectively analyzed a prospectively collected revision shoulder
      arthroplasty cohort to identify shoulder PJI patients treated with a 3-stage
      protocol. Demographics, culture data, range of motion, and patient-reported
      outcomes were collected. Outcomes for patients with shoulder PJI and revision to
      RTSA were compared with patients revised to RTSA for noninfectious indications.
      Significance was defined as P < .05. RESULTS: There were 28 cases of shoulder PJI
      in 27 patients (age, 66.4 +/- 11.2 years,); of these, 21 shoulders were revised
      to RTSA, and 7 shoulders were revised to hemiarthroplasty. There was no recurrent
      infection at a mean 32-month follow-up. One year after surgery, mean forward
      flexion was 110 degrees  +/- 41 degrees  and abduction was 106 degrees  +/- 42
      degrees . Mean final American Shoulder and Elbow Surgeons subjective score was
      66.5 +/- 23.3. The 21 shoulders with PJI revised to RTSA had no differences for
      functional and subjective outcomes compared with revised patients without
      shoulder PJI. CONCLUSIONS: A 3-stage revision protocol for shoulder PJI reliably
      eradicated infection. Patients with PJI revised to RTSA can have similar outcomes
      as patients with noninfectious revision to RTSA.

PMID- 30293859
TI  - Molecular mechanism underlying orofacial antinociceptive activity of
      Vanillosmopsis arborea Baker (Asteraceae) essential oil complexed with beta
      cyclodextrin.
AB  - BACKGROUND: Vanillosmopsis arborea Baker has recognized economic value owing to
      the high content of (-)-alpha-bisabolol (BISA) in the essential oil of its stem
      (EOVA). The antinociceptive effect of EVOA has already been demonstrated, and
      beta-cyclodextrin (betaCD) is known to improve the analgesic effect of various
      substances. PURPOSE: Thus, we aimed to evaluate the orofacial antinociceptive
      effect of a complex containing EOVA-betaCD in rodents. METHODS: EOVA was obtained
      by simple hydrodistillation, and the essential oil was complexed with betaCD. The
      animals (n = 6/group) were treated orally with EOVA-betaCD (10 or 50 mg/kg), or
      vehicle (control), and subjected to cutaneous orofacial nociception (formalin,
      capsaicin, acidic saline or glutamate), corneal (hypertonic saline) or
      temporomandibular (formalin) tests. The expression of FOS protein was analyzed in
      the spinal cord. Molecular docking was performed using the 5-HT3 and M2 receptors
      and BISA. RESULTS: The oral administration of EOVA-betaCD reduced nociceptive
      behaviour. Moreover, EOVA-betaCD decreased FOS expression. The molecular docking
      study indicates that BISA interacts with 5-HT3 and M2 receptors, indicating the
      potential mechanism of action of the tested compound. CONCLUSIONS: Our results
      indicate that EOVA-betaCD possesses orofacial antinociceptive effect, indicating
      that this complex can be used in analgesic drug development.

PMID- 30293860
TI  - Evaluation of a Tool to Identify Child Sex Trafficking Victims in Multiple
      Healthcare Settings.
AB  - PURPOSE: Estimate the prevalence of child sex trafficking (CST) among patients
      seeking care in multiple healthcare settings; evaluate a short screening tool to
      identify victims in a healthcare setting. METHODS: This cross-sectional
      observational study involved patients from 16 sites throughout the U.S.: five
      pediatric emergency departments, six child advocacy centers, and five teen
      clinics. Participants included English-speaking youth ages 11-17 years. For
      emergency department sites, inclusion criteria included a chief complaint of
      sexual violence. Data on several domains were gathered through self-report
      questionnaires and examiner interview. Main outcomes included prevalence of CST
      among eligible youth; sensitivity, specificity, positive/negative predictive
      values, and positive/negative likelihood ratios for a CST screening tool.
      RESULTS: Eight hundred and ten participants included 91 (11.52%) youth from
      emergency departments, 395 (48.8%) from child advocacy centers, and 324 (40.0%)
      from teen clinics. Overall prevalence of CST was 11.1%: 13.2% among emergency
      department patients, 6.3% among child advocacy center patients, and 16.4% among
      teen clinic patients, respectively. The screen had a sensitivity, specificity,
      and positive likelihood ratio of 84.44% (75.28, 91.23), 57.50% (53.80, 61.11),
      and 1.99% (1.76, 2.25), respectively. CONCLUSIONS: This study demonstrates a
      significant rate of CST among patients presenting to emergency departments (for
      sexual violence complaints), child advocacy centers, and teen clinics. A six-item
      screen showed relatively good sensitivity and moderate specificity. Negative
      predictive value was high. Intervention for a "positive" screen may identify
      victims and help prevent high-risk youth from becoming victimized. This is one of
      the first CST screening tools specifically developed and evaluated in the
      healthcare setting.

PMID- 30293861
TI  - Implementation of an Alcohol Medical Amnesty Policy at an Urban University With a
      Collegiate-Based Emergency Medical Services Agency.
AB  - PURPOSE: Medical amnesty policies (MAPs) at universities attemptto encourage
      students to seek emergency medical care by reducing disciplinary sanctions. This
      study analyzed how a MAP affected requests for emergency medical help to a
      collegiate-based emergency medical services (CBEMS) agency for alcohol-related
      issues. METHODS: This before-and-after study analyzed CBEMS call data for the 6
      semesters prior to and after MAP implementation. Extracted data included patient
      demographics, dispatch time, and requests for advanced life support (ALS)
      resources. RESULTS: Following MAP introduction, increases were observed in
      alcohol-related calls/day in the fall semesters (0.84 vs. 0.93; p < 0.01). The
      median time of calls decreased; 1:20 a.m. versus 12:59 a.m. (median difference 21
      minutes, p < 0.001). Finally, ALS was requested less often (9.0% vs. 3.7%; odds
      ratio 0.39; p < 0.01). CONCLUSIONS: MAP implementation at a university with a
      CBEMS is associated with a higher call volume, requests for service that occur
      earlier in the evening, and reduction in ALS requests for alcohol-related
      emergencies.

PMID- 30293862
TI  - Electronic Cigarette Use and Attempts to Quit Smoking Cigarettes Among
      Adolescents in Taiwan.
AB  - PURPOSE: This study assessed the relationship between electronic cigarette (e
      cigarette) use and attempts to quit smoking cigarettes by adolescent smokers in
      Taiwan. METHODS: Data were obtained from the cross-sectional Taiwan Global Youth
      Tobacco Survey conducted annually between 2014 and 2016, which included
      adolescents aged 12-18years. The independent variable was e-cigarette use in the
      previous 30days. The outcome variable was attempts to quit cigarette smoking
      during the previous 12 months. We controlled for the following variables: year of
      survey, gender, grade, monthly income/allowance, numbers of cigarettes per day,
      smoking status of parents and friends, use of other tobacco products, access to
      free tobacco products, assistance in quitting smoking, and exposure to anti
      tobacco campaigns. RESULTS: Among cigarettes smokers, the prevalence of current e
      cigarette use (in the previous 30 days) increased from 9.82% (2014) to 27.46%
      (2016), whereas attempts to quit smoking cigarettes decreased slightly from
      71.31% (2014) to 70.59% (2016). Current e-cigarette use (OR = 1.21) was
      positively associated with attempts to quit cigarette smoking. Smokers who
      observed anti-tobacco media messages (OR = 1.12), attended antismoking classes
      (OR = 1.17), were influenced by warnings on cigarette packages (OR = 3.32), or
      received help to quit (OR = 3.11) were more likely to have attempted to quit
      cigarettes. CONCLUSIONS: We identified factors correlated with attempts to quit
      smoking, and recommend that the government continue monitoring electronic
      cigarette use, combat smoking in the media, provide antismoking classes, and
      expand health warnings on cigarette packages.

PMID- 30293863
TI  - Negative Consequences Associated With Witnessing Severe Violent Events: The Role
      of Control-Related Beliefs.
AB  - PURPOSE: Control-related beliefs are defined as beliefs in one's ability to cause
      an effect in one's environment. With recent increases in violence in some cities,
      understanding the impact of exposure to violence on these beliefs is important.
      The present study examined whether witnessing severe community violence during
      early adolescence was associated with trajectories of control-related beliefs,
      and whether these trajectories were associated with mental and behavioral health
      outcomes in early adulthood. METHOD: Using data from a longitudinal preventive
      intervention study, we modeled trajectories of control-related beliefs using
      growth mixture modeling from 9th through 12th grade. The violence exposure of
      interest was witnessing severe community violence, defined as seeing someone
      being shot, stabbed, or killed. Early adulthood outcomes examined were post high
      school suicide attempt; having a criminal justice record; and having a diagnosis
      of substance use disorder, major depressive disorder, or antisocial personality
      disorder. RESULTS: The latent growth mixture model identified three trajectories
      of control-related beliefs: a low stable trajectory, a high increasing
      trajectory, and a moderate stable trajectory. Participants who were exposed to
      severe violent events were significantly more likely to be in the low trajectory.
      Further, those in the low trajectory were significantly more likely to experience
      several negative outcomes. CONCLUSION: Results suggest that witnessing severe
      forms of community violence impacts control-related belief trajectories and that
      trajectories characterized by low feelings of control are associated with adverse
      outcomes in early adulthood.

PMID- 30293864
TI  - A review on microelectrode recording selection of features for machine learning
      in deep brain stimulation surgery for Parkinson's disease.
AB  - OBJECTIVE: This study seeks to systematically review the selection of features
      and algorithms for machine learning and automation in deep brain stimulation
      surgery (DBS) for Parkinson's disease. This will assist in consolidating current
      knowledge and accuracy levels to allow greater understanding and research to be
      performed in automating this process, which could lead to improved clinical
      outcomes. METHODS: A systematic literature review search was conducted for all
      studies that utilized machine learning and DBS in Parkinson's disease. RESULTS:
      Ten studies were identified from 2006 utilizing machine learning in DBS surgery
      for Parkinson's disease. Different combinations of both spike independent and
      spike dependent features have been utilized with different machine learning
      algorithms to attempt to delineate the subthalamic nucleus (STN) and its
      surrounding structures. CONCLUSION: The state-of-the-art algorithms achieve good
      accuracy and error rates with relatively short computing time, however, the
      currently achievable accuracy is not sufficiently robust enough for clinical
      practice. Moreover, further research is required for identifying subterritories
      of the STN. SIGNIFICANCE: This is a comprehensive summary of current machine
      learning algorithms that discriminate the STN and its adjacent structures for DBS
      surgery in Parkinson's disease.

PMID- 30293866
TI  - Intestinal Dysmotility Syndromes following Systemic Infection by Flaviviruses.
AB  - Although chronic gastrointestinal dysmotility syndromes are a common worldwide
      health problem, underlying causes for these disorders are poorly understood. We
      show that flavivirus infection of enteric neurons leads to acute neuronal injury
      and cell death, inflammation, bowel dilation, and slowing of intestinal transit
      in mice. Flavivirus-primed CD8+ T cells promote these phenotypes, as their
      absence diminished enteric neuron injury and intestinal transit delays, and their
      adoptive transfer reestablished dysmotility after flavivirus infection.
      Remarkably, mice surviving acute flavivirus infection developed chronic
      gastrointestinal dysmotility that was exacerbated by immunization with an
      unrelated alphavirus vaccine or exposure to a non-infectious inflammatory
      stimulus. This model of chronic post-infectious gastrointestinal dysmotility in
      mice suggests that viral infections with tropism for enteric neurons and the
      ensuing immune response might contribute to the development of bowel motility
      disorders in humans. These results suggest an opportunity for unique approaches
      to diagnosis and therapy of gastrointestinal dysmotility syndromes.

PMID- 30293865
TI  - An Endothelial-to-Adipocyte Extracellular Vesicle Axis Governed by Metabolic
      State.
AB  - We have uncovered the existence of extracellular vesicle (EV)-mediated signaling
      between cell types within the adipose tissue (AT) proper. This phenomenon became
      evident in our attempts at generating an adipocyte-specific knockout of caveolin
      1 (cav1) protein. Although we effectively ablated the CAV1 gene in adipocytes,
      cav1 protein remained abundant. With the use of newly generated mouse models, we
      show that neighboring endothelial cells (ECs) transfer cav1-containing EVs to
      adipocytes in vivo, which reciprocate by releasing EVs to ECs. AT-derived EVs
      contain proteins and lipids capable of modulating cellular signaling pathways.
      Furthermore, this mechanism facilitates transfer of plasma constituents from ECs
      to the adipocyte. The transfer event is physiologically regulated by
      fasting/refeeding and obesity, suggesting EVs participate in the tissue response
      to changes in the systemic nutrient state. This work offers new insights into the
      complex signaling mechanisms that exist among adipocytes, stromal vascular cells,
      and, potentially, distal organs.

PMID- 30293867
TI  - Endoscopic versus percutaneous drainage of post-operative peripancreatic fluid
      collections following pancreatic resection.
AB  - BACKGROUND: Post-operative peripancreatic fluid collection (PFC) is a common
      complication following pancreatic resection which can be managed with endoscopic
      or percutaneous drainage. METHODS: Patients who underwent either endoscopic or
      percutaneous drainage of post-operative PFC were extracted from a prospectively
      maintained database. The two groups were matched for surgery type, presence of a
      surgical drain and timing of drainage. RESULTS: Thirty-nine matched patients were
      identified in each group with a median age of 62 years. For primary drainage,
      technical success was achieved in almost all patients in both endoscopic and
      percutaneous groups (100% and 97%, p = NS); clinical success was achieved in 67%
      and 59%, respectively (p = 0.63). At least one "salvage" drainage procedure was
      required in 13 endoscopic patients versus 16 in the percutaneous group. Clinical
      success was achieved following the first salvage. Procedure in 85% of the
      endoscopic patients and 88% of the percutaneous patients (p = 0.62). Stent/drain
      duration (59 vs 33 days, p < 0.001) and number of post-procedural CT studies (2
      vs 1, p = 0.02) were significantly higher in the endoscopic group. There was no
      difference in length of stay, complication, or recurrence between the two groups.
      CONCLUSION: Endoscopic drainage of post-operative PFC appears to be safe and
      effective with comparable success rates and outcomes to percutaneous drainage.

PMID- 30293868
TI  - Clinical criteria for integrated molecular pathology in intraductal papillary
      mucinous neoplasm: less is more.
AB  - BACKGROUND: For pancreatic cysts with negative cytology, Integrated Molecular
      Pathology (IMP) is a malignancy risk score integrating clinical criteria with
      pancreatic cyst fluid DNA profiling. Aside from main pancreatic duct (MPD)
      diameter, integrated clinical criteria are not International Consensus Guidelines
      High-Risk Stigmata. We predicted exclusion of clinical criteria except MPD
      diameter could simplify the IMP and better distinguish invasive/malignant
      disease. METHODS: Records of >1100 patients with IPMN were reviewed
      retrospectively. Sensitivity, specificity, and accuracy of conventional IMP for
      invasive/malignant disease was compared to DNA profile including only MPD >=10mm
      (IMP-10.) Invasive outcomes were invasive-IPMN/adenocarcinoma on surgical
      pathology, pathologic or radiographic evidence of invasive/metastatic disease
      during surveillance. Malignant outcomes included high grade dysplastic IPMN (HGD
      IPMN). RESULTS: 225 patients who met study criteria underwent 283 IMP
      evaluations: 98 followed by surgery, 185 followed by >= 23 months surveillance.
      IMP-10 had greater specificity (90.1% vs. 73.7%) and accuracy (89.8% vs. 74.2%)
      for invasive disease compared to IMP in surgery + surveillance patients, but
      lower sensitivity (77.8% vs. 88.9%). Trends were similar in surgery patients
      alone and malignant outcome analyses. CONCLUSION: IMP-10 excludes less-reliable
      clinical factors resulting in greater accuracy in predicting invasive/malignant
      disease and fewer patients with benign disease being recommended for surgery.

PMID- 30293869
TI  - Multiagent neoadjuvant chemotherapy and tumor response are associated with
      improved survival in pancreatic cancer.
AB  - BACKGROUND: Neoadjuvant therapy (NT) for borderline resectable pancreatic cancer
      (BRPC) has evolved to include multi-agent regimens and chemoradiation. We report
      our experience and compare outcomes of initially resectable pancreatic cancer
      (IRPC) vs BRPC receiving NT across two eras of chemotherapy regimens. METHODS:
      Data were collected retrospectively on pancreaticoduodenectomy patients between
      January 2008 and October 2015. Outcomes and survival were compared based on
      patient, laboratory and treatment factors. RESULTS: 195 patients were included
      and 133 had IRPC and 62 BRPC. IRPC operations were shorter (449 min vs 520 min, p
      = 0.003), had less blood loss (663 ml vs 954 ml, p = 0.002) and involved fewer
      vascular resections (29% vs 76%, p = 0.002). The rate of R0 resection was
      identical (82%, p = 1) and the IRPC group had higher node-positive ratio (19.3%
      vs 7.2% p < 0.0001). 15 patients received a single agent regimen while 47
      received multi-agent regimens with 90% receiving radiation.Survival was similar
      between BRPC and IRPC (log-rank p = 0.7). Histopathologic response (CAP grade 0
      or 1) was not associated with survival (p = 0.13), but completion of >=4 cycles
      of multi-agent pre-operative chemotherapy (p = 0.001) and complete response to NT
      (p = 0.04) were significant predictors of survival. CONCLUSIONS: BRPC patients
      treated with NT have similar morbidity and survival to their IRPC counterparts.
      Pathologic response and modern NT are associated with improved survival.

PMID- 30293870
TI  - The protective effect of Irisin against ischemia-reperfusion injury after
      perforator flap grafting in rats.
AB  - BACKGROUND: Ischemia-reperfusion injury is one of the reasons for failure of flap
      grafting. In the present study, we investigated the protective effect of irisin
      on the survival of perforator flaps in rats. METHODS: A total of 48 adult Sprague
      Dawley rats were divided into 2 groups and subjected to vascular clipping of
      perforator flap. Rats in the experimental group (n = 24) received daily tail
      intravenous injection of irisin (2 ng/g) for 3 days, while the rest rats in the
      control group (n = 24) received injection of saline solution of the same dose. On
      the 7th post-operative day, the surviving area of the flaps were recorded as the
      percentage of the total flap area. Histology study with haematoxylin and eosin
      staining were performed in all flaps. Flaps were also evaluated with lead oxide
      gelatine-enhanced flap angiography. Immunohistochemical study was performed to
      evaluate the expression of ErG, a marker of vascular endothelial cells. The
      tissue of "choke vessels" was excised for quantification of p-Akt/Akt by western
      blot assay on the 7th post-operative day. RESULTS: On the 7th post-operative day,
      the percentage of surviving flap area was significantly larger in the rats with
      irisin administration (experimental group), compared with the control group (P =
      0.011). The density of microvessels was significantly higher in the experimental
      group (P = 0.03) in the histological study and angiography, with a higher
      expression level of ErG in the immunochemical study (P = 0.01). The p-Akt/Akt was
      also higher in the experimental group in Western blotting analysis (P < 0.001).
      CONCLUSION: Irisin has a beneficial effect on protecting perforator flaps from
      ischemic-reperfusion injury following the flap grafting surgery. It was
      potentially achieved by promoting proliferation of vascular endothelial cells
      after flap revascularization. Upregulation of the PI3K/Akt signaling pathway was
      potentially related with this process.

PMID- 30293871
TI  - Early removal of metal stents in walled off pancreatic necrosis.

PMID- 30293872
TI  - Gene expression analysis of embryonic pancreas development master regulators and
      terminal cell fate markers in resected pancreatic cancer: A correlation with
      clinical outcome.
AB  - BACKGROUND: Despite the recent introduction of new drugs and the development of
      innovative multi-target treatments, the prognosis of pancreatic ductal
      adenocarcinoma (PDAC) remains very poor. Even when PDAC is resectable, the rate
      of local or widespread disease recurrence remains particularly high. Currently,
      reliable prognostic biomarkers of recurrence are lacking. We decided to explore
      the potential usefulness of pancreatic developmental regulators as biomarkers of
      PDAC relapse. METHODS: We analyzed by quantitative real-time PCR the mRNA of
      selected factors involved either in pancreatic organogenesis (ISL1, NEUROD1,
      NGN3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1 and PTF1alpha) or associated with
      terminally committed pancreatic cells (CHGA, CHGB, GAD2, GCG, HNF6alpha, INS,
      KRT19, SYP) in 17 PDAC cell lines and in frozen tumor samples from 41 PDAC
      patients. RESULTS: High baseline levels of the ISL1, KRT19, PAX6 and PDX1 mRNAs
      in PDAC cell lines, were risk factors for time-dependent xenograft appearance
      after subcutaneous injection in CD1-Nude mice. Consistently, in human PDAC
      samples, high levels of KRT19 mRNA were associated with reduced overall survival
      and earlier recurrence. Higher levels of PDX1 or PAX6 mRNAs were instead
      associated with a higher frequency of local recurrence. CONCLUSIONS: Our findings
      suggest that selected factors associated with pancreas development or its
      terminal differentiation might be implicated in mechanisms of PDAC progression
      and/or metastatic spread and that the measurement of their mRNA in tumors might
      be potentially used to improve patient prognostic stratification and prediction
      of the relapse site.

PMID- 30293873
TI  - Prognostic Effect of Adenosine-related Genetic Variants in Metastatic Colorectal
      Cancer Treated With Bevacizumab-based Chemotherapy.
AB  - BACKGROUND: Adenosine has an immunosuppressive and angiogenic modulation of the
      tumor microenvironment. The present study explored the efficacy of single
      nucleotide polymorphisms (SNPs) in adenosine-related molecules for patients with
      metastatic colorectal cancer treated with bevacizumab-based chemotherapy.
      PATIENTS AND METHODS: We analyzed genomic DNA extracted from 451 samples from 3
      independent cohorts: a discovery cohort of 107 patients treated with FOLFIRI (5
      fluorouracil, leucovorin, oxaliplatin, irinotecan) plus bevacizumab in FIRE-3
      (ClinicalTrials.gov identifier, NCT00433927); a validation cohort of 215 patients
      with FOLFIRI plus bevacizumab in TRIBE (ClinicalTrials.gov identifier,
      NCT00719797); and a control cohort of 129 patients treated with FOLFIRI plus
      cetuximab in FIRE-3. The relationship between the selected SNPs and clinical
      outcomes was analyzed. RESULTS: In the discovery cohort, patients with any C
      allele in CD39 rs11188513 had significantly shorter median progression-free
      survival compared with those with the T/T variant (11.3 vs. 13.1 months; hazard
      ratio [HR], 1.70; 95% confidence interval [CI], 1.04-2.77; P = .022) on
      univariate analysis. Also, their overall survival (OS) was shorter (27.4 vs. 49.9
      months; HR, 2.10; 95% CI, 1.07-4.10; P = .031) on univariate and multivariable
      analyses. The significant association between CD39 rs11188513 and OS was
      confirmed in the validation cohort (25.8 vs. 31.6 months; HR, 1.53; 95% CI, 1.09
      2.15; P = .013). CD73 rs2229523 and A2BR rs2015353 in the discovery cohort and
      CD39 rs2226163 in the validation cohort showed significant correlations with OS
      on univariate and multivariable analyses. None of SNPs were significant in the
      cetuximab control cohort. CONCLUSION: Selected SNPs in the adenosine pathway
      could affect the clinical outcomes of patients with metastatic colorectal cancer
      treated with FOLFIRI plus bevacizumab.

PMID- 30293874
TI  - Erratum to "Time trends and short term projections of cancer prevalence in
      France" [Cancer Epidemiol. 56 (2018) 97-105].

PMID- 30293875
TI  - A predictive method for hepatitis disease diagnosis using ensembles of neuro
      fuzzy technique.
AB  - BACKGROUND: Hepatitis is an inflammation of the liver, most commonly caused by a
      viral infection. Supervised data mining techniques have been successful in
      hepatitis disease diagnosis through a set of datasets. Many methods have been
      developed by the aids of data mining techniques for hepatitis disease diagnosis.
      The majority of these methods are developed by single learning techniques. In
      addition, these methods do not support the ensemble learning of the data.
      Combining the outputs of several predictors can result in improved accuracy in
      classification problems. This study aims to propose an accurate method for the
      hepatitis disease diagnosis by taking the advantages of ensemble learning.
      METHODS: We use Non-linear Iterative Partial Least Squares to perform the data
      dimensionality reduction, Self-Organizing Map technique for clustering task and
      ensembles of Neuro-Fuzzy Inference System for predicting the hepatitis disease.
      We also use decision trees for the selection of most important features in the
      experimental dataset. We test our method on a real-world dataset and present our
      results in comparison with the latest results of previous studies. RESULTS: The
      results of our analyses on the dataset demonstrated that our method performance
      is superior to the Neural Network, ANFIS, K-Nearest Neighbors and Support Vector
      Machine. CONCLUSIONS: The method has potential to be used as an intelligent
      learning system for hepatitis disease diagnosis in the healthcare.

PMID- 30293876
TI  - Candida auris: a global fungal public health threat.

PMID- 30293878
TI  - Long-term safety and efficacy of alirocumab in patients with heterozygous
      familial hypercholesterolemia: An open-label extension of the ODYSSEY program.
AB  - BACKGROUND AND AIMS: ODYSSEY OLE (open-label extension; NCT01954394) included
      patients diagnosed with heterozygous familial hypercholesterolemia (HeFH),
      receiving maximally tolerated statins, who had completed one of four Phase 3
      double-blind parent studies (all 18 months' duration), with the aim to assess
      longer-term safety and efficacy of alirocumab. METHODS: Patients received
      starting dose alirocumab 75 mg every 2 weeks (Q2W; patients from FH I, FH II, and
      LONG TERM) or alirocumab 150 mg Q2W (patients from HIGH FH). Low-density
      lipoprotein cholesterol (LDL-C) levels were blinded to the patient and physician
      until Week 8; from Week 8, LDL-C levels were communicated to physicians. From
      Week 12, dose adjustment from 75 to 150 mg Q2W, or vice versa, was possible per
      physician's clinical judgment according to patient's LDL-C levels. RESULTS:
      Patients who had received alirocumab (n = 655) compared with placebo (n = 330) in
      the parent studies exhibited similar rates of treatment-emergent adverse events
      (TEAEs; 87.3% vs. 83.9%) during OLE (2.5 years median alirocumab exposure).
      Overall, 33 patients (3.4%) experienced TEAEs leading to permanent treatment
      discontinuation. At Week 8, alirocumab reduced mean LDL-C by 44.2% (reduction
      from 151.9 mg/dL at parent study baseline to 84.9 mg/dL); reduction in LDL-C was
      consistent to Week 96 of OLE. Reductions in lipid parameters were similar
      regardless of treatment allocation in the parent study. CONCLUSIONS: In patients
      with HeFH, no unexpected long-term safety concerns were observed with alirocumab
      compared with previously published data; durability of LDL-C-lowering over 3
      years (including 1.5 years of parent trials) was demonstrated.

PMID- 30293877
TI  - Multiple introductions and subsequent transmission of multidrug-resistant Candida
      auris in the USA: a molecular epidemiological survey.
AB  - BACKGROUND: Transmission of multidrug-resistant Candida auris infection has been
      reported in the USA. To better understand its emergence and transmission dynamics
      and to guide clinical and public health responses, we did a molecular
      epidemiological investigation of C auris cases in the USA. METHODS: In this
      molecular epidemiological survey, we used whole-genome sequencing to assess the
      genetic similarity between isolates collected from patients in ten US states
      (California, Connecticut, Florida, Illinois, Indiana, Maryland, Massachusetts,
      New Jersey, New York, and Oklahoma) and those identified in several other
      countries (Colombia, India, Japan, Pakistan, South Africa, South Korea, and
      Venezuela). We worked with state health departments, who provided us with
      isolates for sequencing. These isolates of C auris were collected during the
      normal course of clinical care (clinical cases) or as part of contact
      investigations or point prevalence surveys (screening cases). We integrated data
      from standardised case report forms and contact investigations, including travel
      history and epidemiological links (ie, patients that had shared a room or ward
      with a patient with C auris). Genetic diversity of C auris within a patient, a
      facility, and a state were evaluated by pairwise differences in single-nucleotide
      polymorphisms (SNPs). FINDINGS: From May 11, 2013, to Aug 31, 2017, isolates that
      corresponded to 133 cases (73 clinical cases and 60 screening cases) were
      collected. Of 73 clinical cases, 66 (90%) cases involved isolates related to
      south Asian isolates, five (7%) cases were related to South American isolates,
      one (1%) case to African isolates, and one (1%) case to east Asian isolates. Most
      (60 [82%]) clinical cases were identified in New York and New Jersey; these
      isolates, although related to south Asian isolates, were genetically distinct.
      Genomic data corroborated five (7%) clinical cases in which patients probably
      acquired C auris through health-care exposures abroad. Among clinical and
      screening cases, the genetic diversity of C auris isolates within a person was
      similar to that within a facility during an outbreak (median SNP difference three
      SNPs, range 0-12). INTERPRETATION: Isolates of C auris in the USA were
      genetically related to those from four global regions, suggesting that C auris
      was introduced into the USA several times. The five travel-related cases are
      examples of how introductions can occur. Genetic diversity among isolates from
      the same patients, health-care facilities, and states indicates that there is
      local and ongoing transmission. FUNDING: US Centers for Disease Control and
      Prevention.

PMID- 30293879
TI  - Post-stroke follow-up: Time to organize.
AB  - BACKGROUND/OBJECTIVE: General practitioners (GPs) are pivotal in the organization
      of the entire post-stroke management system. This study aimed to examine the
      sequelae of chronic post-stroke patients and to assess whether the medical follow
      up organized by GPs is truly in accordance with current recommendations and
      patients' clinical needs. METHODS: This was an observational study including
      chronic post-stroke patients after a first stroke. Their post-stroke follow-ups
      (visits to GPs and specialist doctors) were compared with guidelines and with
      clinical needs as evaluated through a number of questionnaires. RESULTS: Overall,
      53.2% of patients visited a neurologist as recommended and, although 49.4% had
      neuropsychiatric consequences, only 6.3% visited a psychiatrist. Similarly, while
      34.2% had significant post-stroke disability, only 6.3% saw a rehabilitation
      physician. CONCLUSION: Taking into account not only cardiovascular prevention,
      but all post-stroke consequences, medical follow-ups as organized by GPs were not
      in accordance with recommendations and failed to take advantage of the currently
      available multidisciplinary resources required to improve patients' needs.

PMID- 30293880
TI  - Early contribution of Alexandria medical school to the anatomy, physiology and
      pathology of the nervous system.
AB  - Alexandria's famous medical school was established about 300 BC. It was the seat
      of learning for many Greco-Roman physicians. The physiologist Erasistratus, the
      anatomist Herophilus - named the Father of Anatomy were outstanding pioneers.
      Their work and discoveries of the nervous system, its structure and function, are
      described. In the 2nd century AD they were succeeded by Rufus of Ephesus - the
      medical link between Hippocrates and Galen, - and Aretaeus a leading anatomist
      and physician in this period.

PMID- 30293881
TI  - New findings in facial-onset sensory and motor neuronopathy (FOSMN) syndrome.
AB  - Facial-onset sensory and motor neuronopathy (FOSMN) syndrome represents a rare,
      slowly progressive, lower motor neuron disease with sensory compromise, involving
      mainly the face, bulbar region and upper limbs. However, non-motor symptoms and
      neurogenetic studies have rarely been evaluated in large case series. In the
      present study, 10 unrelated Brazilian patients with FOSMN syndrome underwent
      extensive clinical, laboratory, neurophysiological and neurogenetic assessment.
      Median age at symptom onset was 52.1 years, and men and women were equally
      affected. Patients presented with hemifacial or bilateral facial paresthesia and
      weakness, which evolved with dysphagia, dysphonia, and facial and tongue atrophy
      and, finally, a dropped-head, upper limb weakness and syringomyelia-like sensory
      disturbances in the upper limbs. All 10 patients showed chronic diffuse
      neurogenic compromise of bulbar, cervical and thoracic myotomes, and abnormal
      blink reflex tests. A positive family history of neurodegeneration was identified
      in six cases, and revealed pathogenic gene variants in three families (involving
      VCP, TARDBP and CHCHD10). Thus, our case series has revealed new findings
      regarding FOSMN syndrome: (i) its clinical course is not always benign, with
      poorer prognoses associated with dropped-head syndrome and early bulbar
      compromise; (ii) FOSMN syndrome may be part of a complex familial
      neurodegenerative spectrum; and (iii) a definite genetic basis may be observed in
      some cases.

PMID- 30293882
TI  - Myelin oligodendrocyte glycoprotein antibodies in neuromyelitis optica spectrum
      disorder.
AB  - Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory disease
      of the central nervous system characterized, in particular, by disabling episodes
      of optic neuritis and longitudinal extensive transverse myelitis. Its main
      pathogenic characteristic is the presence of anti-aquaporin-4 antibodies (AQP4
      Abs) in the serum of affected patients. However, a proportion of patients with
      the typical NMOSD phenotype are, in fact, negative (seronegative) for AQP4-Abs
      and, within this category of patients, a proportion of them instead express
      antibodies to myelin oligodendrocyte glycoprotein (MOG-Abs). The presence of MOG
      Abs in the sera of seronegative NMOSD patients is more frequently associated with
      monophasic disease and moderate symptom severity, and also appears to predict a
      better outcome. The present report is a review of the clinical and immunological
      features of MOG-Ab-positive NMOSD.

PMID- 30293883
TI  - Acute brachial plexus lesion complicating a stun-gun assault.

PMID- 30293884
TI  - Clinical efficacy of tacrolimus for treating myasthenia gravis and its influence
      on lymphocyte subsets.
AB  - BACKGROUND: This study aimed to determine the clinical efficacy and effects of
      tacrolimus in treating myasthenia gravis (MG). METHODS: A total of 45 outpatients
      and inpatients were divided into a tacrolimus group (n=15) and non-tacrolimus
      group (n=30): those in the former group were treated with 3mg/day of tacrolimus
      for 24 weeks, while those in the latter (control) group took other
      immunosuppressants (prednisone, azathioprine combined with prednisone). Each
      group was evaluated at weeks 4, 8, 12, 16, 20 and 24 by Myasthenia Gravis
      Foundation of America Quantitative Myasthenia Gravis (MGFA-QMG) Test, activities
      of daily living (ADL) profiles, and manual muscle (MMT) and fatigue tests.
      Dynamic changes in CD4+CD25+high cells were tested by flow cytometry.
      Inflammatory cytokines were also evaluated in the tacrolimus group. RESULTS:
      Efficacy index scores decreased significantly compared with baseline at every
      test week in both groups (P<0.01), although improvements were more evident with
      than without tacrolimus treatment (F=9.312, P<0.01 vs. F=24.551, P<0.01 and
      F=10.710, P<0.01). At week 24, peripheral blood CD4+CD25+high T cells with
      tacrolimus decreased significantly (P<0.01), but increased significantly without
      tacrolimus (P<0.01). During treatment, CD19+BAFF-R B cells in peripheral blood
      decreased in both groups (P<0.05). Interferon (IFN)-gamma concentrations in
      peripheral blood also diminished significantly with tacrolimus (P<0.01).
      CONCLUSION: A relatively low dose of tacrolimus can affect multiple immune-system
      targets and, thus, can treat MG effectively in terms of both clinical symptoms
      and immunological responses.

PMID- 30293885
TI  - Danish Trends in Major Amputation After Vascular Reconstruction in Patients With
      Peripheral Arterial Disease 2002-2014.
AB  - INTRODUCTION: Contemporary information on major amputations after
      revascularisation in Denmark is sparse. This population based national study
      aimed to determine outcomes following revascularisation for PAD and to identify
      predictors of major amputation after revascularisation, including geographical
      variation. METHODS: Data on patients with PAD undergoing revascularisation
      (endovascular, open, and hybrid procedures) from 2002 to 2014 were obtained from
      the Danish Vascular Registry and linked with information from population based
      healthcare and administrative databases. Cox proportional hazards regression was
      used to assess the relationship between major amputation and the various
      associated factors. RESULTS: In all 25,982 first time vascular reconstructions
      for PAD were performed between 2002 and 2014 and major amputations were performed
      in 2883 (11.1%) of the patients. The total number of revascularisations increased
      up to 2010 and thereafter numbers decreased slightly. A trend towards
      endovascular revascularisation as first time revascularisation was seen (36.6% in
      2002 vs. 59.0% in 2014, p < .001). Median time from first revascularisation to
      major amputation was 4.66 months (range 0.03-146.88 months), and 63.1% of major
      amputations were performed within one year following revascularisation. No change
      in the number of amputations performed within one year after revascularisation
      was found during the study (p = .251). The strongest predictor for major
      amputations was ulcers/gangrene (HR 8.06, CI 7.11-9.13, p < .001) at the time of
      revascularisation. Geographic variation for intensity of revascularisation was
      observed and geographic differences in amputation free survival for patients with
      intermittent claudication and ulcers/gangrene were found. CONCLUSION: Although
      more patients with PAD undergo revascularisation, one in 10 still ends up with a
      major amputation of the lower limb. The risk of amputation was highly associated
      with the severity of the vascular disease at the time of revascularisation, with
      ulcers/gangrene as the strongest predictor. Geographic differences in vascular
      treatment intensity were found, but these failed to explain the differences in
      risk of major amputation after revascularisation across catchment areas.

PMID- 30293886
TI  - Acute Mesenteric Ischaemia and Coralliform Aorta.

PMID- 30293887
TI  - Long-term Survival and Risk Analysis in 136 Consecutive Patients With Type B
      Aortic Dissection Presenting to a Single Centre Over an 11 Year Period.
AB  - OBJECTIVES: To evaluate, in patients with acute type B aortic dissection, the
      results of medical and endovascular treatment in a large single centre experience
      and to investigate the clinical and imaging features on presentation that relate
      to poor outcome. METHODS: This was a retrospective analysis of prospectively
      collected clinical and CT imaging data. Consecutive patients (136) with acute
      type B aortic dissection were included in the study over an 11 year period. The
      characteristics of patients receiving endovascular (complicated) or medical
      treatment (uncomplicated) were compared. Kaplan-Meier estimators were used to
      estimate cumulative overall survival and survival free of aortic events. Factors
      associated with overall and aortic event free survival were also explored using
      Cox proportional hazards models. RESULTS: The mean follow up was 51 months (1
      132), during which time 33 deaths and 48 aortic events occurred. At one and five
      years, overall survival was 94.0% and 74.8%, respectively, and freedom from
      aortic events was 75.6% and 58.7%. There was no difference in all cause survival
      and aortic event free survival at one and five years between the patients treated
      endovascularly and those receiving medical treatment alone. Risk analysis for
      aortic events demonstrated the maximum size of the proximal entry tear, the
      maximum thoracic aortic diameter, and the thoracic aortic false lumen maximum
      diameter to have a significant effect on the incidence of aortic events.
      CONCLUSIONS: Active management of patients with type B aortic dissection results
      in good long-term survival even in the presence of features traditionally
      associated with adverse outcomes. All patients require close lifetime
      surveillance as aortic events continue to occur during follow up even after
      endografting.

PMID- 30293888
TI  - Management of Limb Thrombosis After Endovascular Aneurysm Repair: An Endovascular
      Solution for an Endovascular Problem.

PMID- 30293889
TI  - Correcting for Body Surface Area Identifies the True Prevalence of Abdominal
      Aortic Aneurysm in Screened Women.
AB  - OBJECTIVE/BACKGROUND: Recently, the prevalence of abdominal aortic aneurysm (AAA)
      using screening strategies based on elevated cardiovascular disease (CVD) risk
      was reported. AAA was defined as a diameter >=30 mm, with prevalence of 6.1% and
      1.8% in men and women respectively, consistent with the widely reported AAA
      predominant prevalence in males. Given the obvious differences in body size
      between sexes this study aimed to re-evaluate the expanded CVD risk based AAA
      screening dataset to determine the effect of body size on sex specific AAA
      prevalence. METHODS: Absolute (26 and 30 mm) and relative (aortic size index
      [ASI] equals the maximum infrarenal aorta diameter (cm) divided by body surface
      area (m2), ASI >= 1.5) thresholds were used to assess targeted AAA screening
      groups (n = 4115) and compared with a self reported healthy elderly control group
      (n = 800). RESULTS: Male AAA prevalence was the same using either the 30 mm or
      ASI >=1.5 aneurysm definitions (5.7%). In females, AAA prevalence was
      significantly different between the 30 mm (2.4%) and ASI >= 1.5 (4.5%) or the 26
      mm (4.4%) thresholds. CONCLUSION: The results suggest the purported male
      predominance in AAA prevalence is primarily an artefact of body size differences.
      When aortic size is adjusted for body surface area there is only a modest sex
      difference in AAA prevalence. This observation has potential implications in the
      context of the ongoing discussion regarding AAA screening in women.

PMID- 30293890
TI  - [Angiomatoid fibrous histiocytoma of the radial pulse groove].
AB  - BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a slowly progressing rare
      soft-tissue tumour of moderate malignant potential. It is most commonly seen in
      children and young adults. Clinically, the lesion is easily confused with a
      haematoma or soft-tissue haemangioma, and the radiological aspects are not
      specific. PATIENTS AND METHODS: A 16-year-old male patient presented with a
      nodular lesion situated very close to the right radial artery, vein and nerve and
      which had been developing for several years. Surgical resection was carried out
      with sparing of vasculonervous and functional structures. Histological
      examination revealed a tumour of plurinodular architecture, surrounded by a
      fibrous pseudocapsule consisting of histiocytoid or fusiform cells in short
      bundles associated with a mononuclear inflammatory reaction of nodular
      architecture. The tumour cells expressed the following immunomarkers: desmin,
      smooth muscle actin, CD99, and epithelial membrane antigen. Fusion transcript
      EWSR1-ATF1 was found. DISCUSSION: In this case, as occurs in the literature, a
      diagnosis of AFH was not made on clinical examination or imaging. The enlarged
      excision normally recommended was greatly restricted in our patient due to the
      complex localization of the lesion, which was in contact with major anatomical
      structures. The diagnosis was based on histological examination of the surgical
      excision and identification of the fusion gene. Long-term follow-up is required
      to detect local recurrence or metastasis. Management is decided in
      multidisciplinary meetings.

PMID- 30293891
TI  - Indeterminate biliary strictures differential diagnosis: Back to the future.

PMID- 30293892
TI  - Which heart rate variability index is an independent predictor of mortality in
      cirrhosis.
AB  - BACKGROUND: Liver cirrhosis is associated with reduced heart rate variability
      (HRV), which indicates impaired integrity of cardiovascular control in this
      patient population. There are several different indices for HRV quantification.
      The present study was designed to: 1) determine which of the HRV indices is best
      at predicting mortality in patients with cirrhosis; 2) verify if such ability to
      predict mortality is independent of the severity of hepatic failure. METHODS: Ten
      minutes electrocardiogram was recorded in 74 patients with cirrhosis. Heart rate
      fluctuations were quantified using statistical, geometrical and non-linear
      analysis. The patients were followed-up for 18 months and information was
      collected on the occurrence of death/liver transplantation. RESULTS: During the
      follow-up period, 24 patients (32%) died or were transplanted for hepatic
      decompensation. Cox's regression analysis showed that SDNN (total HRV), cSDNN
      (corrected SDNN), SD1 (short-term HRV), SD2 (long-terms HRV) and spectral indices
      could predict survival in these patients. However, only SD2 and cSDNN were shown
      to be independent of MELD in predicting survival. The prognostic value of HRV
      indices was independent of age, gender, use of beta blockers, and the aetiology
      of liver disease. CONCLUSION: Two HRV indices were identified that could predict
      mortality in patients with cirrhosis, independently of MELD. These indices are
      potentially useful tools for survival prediction.

PMID- 30293893
TI  - Ghrelin transport across the blood-brain barrier can occur independently of the
      growth hormone secretagogue receptor.
AB  - OBJECTIVE: The blood-brain barrier (BBB) regulates the entry of substrates and
      peptides into the brain. Ghrelin is mainly produced in the stomach but exerts its
      actions in the central nervous system (CNS) by crossing the BBB. Once present in
      the CNS, ghrelin can act in the hypothalamus to regulate food intake, in the
      hippocampus to regulate neurogenesis, and in the olfactory bulb to regulate food
      seeking behavior. The goal of this study was to determine whether the primary
      signaling receptor for ghrelin, the growth hormone secretagogue receptor (GHSR),
      mediates the transport of ghrelin from blood to brain. METHODS: We utilized the
      sensitive and quantitative multiple-time regression analysis technique to
      determine the transport rate of mouse and human acyl ghrelin (AG) and desacyl
      ghrelin (DAG) in wildtype and Ghsr null mice. We also measured the regional
      distribution of these ghrelin peptides throughout the brain. Lastly, we
      characterized the transport characteristics of human DAG by measuring the
      stability in serum and brain, saturability of transport, and the complete
      transfer across the brain endothelial cell. RESULTS: We found the transport rate
      across the BBB of both forms of ghrelin, AG, and DAG, were not affected by the
      loss of GHSR. We did find differences in the transport rate between the two
      isoforms, with DAG being faster than AG; this was dependent on the species of
      ghrelin, human being faster than mouse. Lastly, based on the ubiquitous
      properties of ghrelin throughout the CNS, we looked at regional distribution of
      ghrelin uptake and found the highest levels of uptake in the olfactory bulb.
      CONCLUSIONS: The data presented here suggest that ghrelin transport can occur
      independently of the GHSR, and ghrelin uptake varies regionally throughout the
      brain. These findings better our understanding of the gut-brain communication and
      may lead to new understandings of ghrelin physiology.

PMID- 30293894
TI  - The regulation of insulin secretion via phosphoinositide-specific phospholipase
      Cbeta signaling.
AB  - Phospholipase Cbeta (PLCbeta) is a membrane-associated enzyme activated by
      membrane receptors, especially G-protein coupled receptors (GPCRs). It propagates
      intracellular signaling by mediating phospholipid metabolism and generating key
      second messengers, such as inositol triphosphate and diacylglycerol, leading to
      intracellular Ca2+ mobilization and activation of kinases, such as protein
      kinases C. In pancreatic beta-cells, PLCbeta-mediated signaling activated by
      various factors, such as free fatty acids and neuronal and hormonal ligands, has
      been confirmed as being involved in the regulation of insulin secretion, and
      PLCbetas have been regarded as essential mediators for augmenting insulin
      secretion. In this review, we describe the physiological function of PLCbetas in
      the regulation of glucose-stimulated insulin secretion and discuss emerging data
      on GPCR/PLCbeta signaling that is being developed as a target for the treatment
      of diabetes mellitus.

PMID- 30293895
TI  - Analysis of clinical characteristics and S gene sequences in chronic asymptomatic
      HBV carriers with low-level HBsAg.
AB  - BACKGROUND: During the natural hepatitis B virus (HBV) infection process, some
      infected subjects are characterized by a sustained low serum HBV surface antigen
      (HBsAg) expression level. Most members in this population are chronic
      asymptomatic HBV carriers (ASCs). To elucidate the mechanism underlying low-level
      HBsAg expression in ASCs, we sequenced the HBV S gene in these patients to reveal
      specific sequence characteristics. METHODS: Overall, 1308 cases of chronic ASCs
      were grouped according to their HBsAg serum expression levels (10 IU/mL). The
      clinical characteristics of the population were analysed in detail. The HBV S
      gene was sequenced from 276 ASC cases with low-level HBsAg expression.
      Additionally, 100 of 1032 ASC cases with high-level HBsAg expression were
      randomly selected for HBV S gene sequencing based on age matching according to
      the low-level HBsAg group. A comparative analysis was conducted with the HBV S
      gene sequences from ASCs with low HBsAg expression and the HBV reference S gene
      sequences from ASCs with high HBsAg expression. RESULTS: The population with low
      level HBsAg expression displayed the following primary clinical characteristics:
      mostly chronic asymptomatic HBV carriers, older age (mean age 55.09 years),
      HBsAg/anti-HBe/anti-HBc (core) positivity as the main serological pattern
      (97.1%), low HBV DNA replication (1.32 +/- 1.60 log10 IU/mL), a low HBV-DNA
      positive rate (45.65%) and primarily genotype B (82.54%) and serotype adw
      (84.13%). The comparative analysis of the HBV S gene sequences from ASCs with low
      level HBsAg showed significant mutations (including co-mutations) on both sides
      of the main hydrophilic region (MHR). CONCLUSION: Significant mutations in
      multiple regions and at multiple sites (including co-mutations) on both sides of
      the MHR may be one cause of the low HBsAg expression level in this population.

PMID- 30293896
TI  - Evidence of HCV recovery after therapy of hepatitis C virus infection by direct
      acting antivirals.

PMID- 30293897
TI  - Commentary: Evidence based interventions for children and adolescents with Autism
      Spectrum Disorders.

PMID- 30293898
TI  - Late growth of infantile hemangiomas in children >3 years of age: A retrospective
      study.
AB  - BACKGROUND: The proliferative phase of infantile hemangiomas (IHs) is usually
      complete by 9 months of life. Late growth beyond age 3 years is rarely reported.
      OBJECTIVE: To describe the demographic and clinic characteristics of a cohort of
      patients with late growth of IH, defined as growth in a patient >3 years of age.
      METHODS: A multicenter, retrospective cohort study. RESULTS: In total, 59
      patients, 85% of which were female, met the inclusion criteria. The mean first
      episode of late growth was 4.3 (range 3-8.5) years. Head and neck location
      (55/59; 93%) and presence of deep hemangioma (52/59; 88%) were common
      characteristics. Posterior fossa malformations, hemangiomas, arterial anomalies,
      cardiac defects, eye abnormalities (PHACE) syndrome was noted in 20 of 38 (53%)
      children with segmental facial IH. Systemic therapy (corticosteroid or beta
      blocker) was given during infancy in 58 of 59 (98%) and 24 of 59 (41%) received
      systemic therapy (beta-blockers) for late IH growth. LIMITATIONS: The
      retrospective nature and ascertainment by investigator recall are limitations of
      the study. CONCLUSION: Late IH growth can occur in children after 3 years of age.
      Risk factors include head and neck location, segmental morphology, and
      involvement of deep dermal/subcutaneous tissues.

PMID- 30293900
TI  - Variation of surgery clerkship grades in US medical schools.
AB  - BACKGROUND: Despite efforts at standardization, evaluation and reporting of
      clerkships remains highly variable. This study reviews the current spectrum of
      surgical clerkship grading. METHODS: Data were reviewed for every medical school
      from which an application was received to a single surgery residency program in
      2017 and were evaluated for core surgical clerkship grading systems,
      distributions, and components. Fischer's exact tests and Wilcoxon-Mann-Whitney
      tests were used for analysis. RESULTS: 133 (49 private) schools were evaluated.
      Geographic distribution:34 Northeast, 50 South, 31 Midwest and 18 West. 120
      reported grading tiers, with public schools (95%) more likely than private (80%)
      to report this (p = 0.02). The number of grading categories ranged from 2 to 11;
      90% with 3-5. Over 25% of the schools gave >=40% of students the highest grade;
      median of 30% in the highest tier. CONCLUSIONS: Significant variation exists in
      core surgery clerkship grading between schools. Similarly, a sizeable difference
      exists in how grades are calculated and the reporting systems used. Standardizing
      grading schemes across medical schools would be beneficial.

PMID- 30293899
TI  - Hospitalized patients with stress hyperglycemia: incidence of diabetes and
      mortality on follow-up.
AB  - INTRODUCTION: The study objective was to estimate during post-discharge follow-up
      the incidence of diabetes and to ascertain mortality in hospitalized patients,
      classified during follow-up as having stress hyperglycemia (SH) or normoglycemia
      (NG) based on blood glucose levels. MATERIAL AND METHODS: A retrospective cohort
      of non-diabetic adults with SH (> 140mg/dl and HbA1c <6.5%) or NG (all blood
      glucose values <= 140mg/dl) was used. RESULTS: There were 3981 patients with NG
      and 884 with SH. During the observation period (median follow-up of 1.83 years),
      there were 255 cases of diabetes and 831 deaths. The cumulative incidence of
      diabetes per year was 1.59% (95% CI: 1.23-2.06) in patients with NG and 7.39%
      (95% CI: 5.70-9.56) in those with SH. SH was significantly associated to diabetes
      (crude HR 1.33, 95% CI: 1.13-1.73, p .025), even after adjusting for age and sex
      (adjusted HR 1.38, 95% CI 1.06-1.78, p .014). The mortality rate at one year was
      10.07% (95% CI: 9.18-11.05) in NG patients and 13.24% (95% CI: 11.17-15.65) in SH
      patients. The sub-hazard ratio of developing diabetes considering death as a
      competitive event was 1.41 (95% CI 1.29-1.53, p <.001). CONCLUSIONS: SH is a risk
      factor for diabetes. There were no differences in mortality during follow-up, but
      death appears to be a competitive event in development of diabetes in this
      population.

PMID- 30293901
TI  - Circulating Thrombospondin-2 enhances prediction of malignant intraductal
      papillary mucinous neoplasm.
AB  - BACKGROUND: IPMNs are cystic pancreatic lesions with variable malignant
      potential. Thrombospondin-2 (THBS2)-an endogenous, anti-angiogenic matrix
      glycoprotein-may modulate tumor progression. We hypothesized that circulating
      levels of THBS2 could aid in preoperative prediction of malignant IPMN. METHODS:
      Preoperative serum/plasma samples were procured from patients undergoing surgery.
      Circulating levels of THBS2 were measured (enzyme-linked immunosorbent assay) and
      compared to surgical pathology IPMN dysplastic grade. RESULTS: 164 patients
      underwent THBS2 testing (100 Low/Moderate-IPMN; 64 High-Grade/Invasive-IPMN).
      Circulating THBS2 (mean +/- SD) was greater in High-Grade/Invasive-IPMN than
      Low/Moderate-grade IPMN (26.6 +/- 12.7 ng/mL vs. 20.4 +/- 8.2 ng/mL; P < 0.001).
      THBS2 (AUC = 0.65) out-performed CA19-9 (n = 144; AUC = 0.59) in predicting IPMN
      grade. The combination of THBS2, CA19-9, radiographic main-duct involvement, main
      duct diameter, age, sex, and BMI (AUC 0.82; n = 137) provided a good prediction
      model for IPMN grade. CONCLUSION: Circulating THBS2 is correlated with IPMN
      dysplasia grade. THBS2 alone did not strongly predict IPMN grade but rather
      strengthened prediction models for High-Grade/Invasive IPMN when combined with
      other clinical/biomarker data.

PMID- 30293902
TI  - Identification of Potential Novel Candidates for Understanding Racial Differences
      in Prostate Cancer.

PMID- 30293903
TI  - Radiofrequency-induced Thermochemotherapy for Recurrent Non-muscle-invasive
      Bladder Cancer: A New Treatment for an Unmet Need?

PMID- 30293904
TI  - Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer
      Glutamine Addiction with Immune Evasion.
AB  - BACKGROUND: Glutamine addiction is a hallmark of clear cell renal cell carcinoma
      (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is
      unclear. This knowledge may yield novel immunotherapeutic opportunities.
      OBJECTIVE: To seek a potential therapeutic target in glutamine-addicted ccRCC.
      DESIGN, SETTING, AND PARTICIPANTS: Tumors from ccRCC patients from a Shanghai
      cohort and ccRCC tumor data from The Cancer Genome Atlas (TCGA) cohort were
      analyzed. In vivo and in vitro studies were conducted with fresh human ccRCC
      tumors and murine tumor cells. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Immune cell numbers and functions were analyzed by flow cytometry. Glutamine and
      cytokine concentrations were determined. Survival was compared between different
      subpopulations of patients using Kaplan-Meier and Cox regression analyses.
      RESULTS AND LIMITATIONS: We found that in ccRCC, high interleukin (IL)-23
      expression was significantly associated with poor survival in both TCGA (overall
      survival [OS] hazard ratio [HR]=2.04, cancer-specific survival [CSS] HR=2.95; all
      p<0.001) and Shanghai (OS HR=2.07, CSS HR=3.92; all p<0.001) cohorts. IL-23
      blockade prolongs the survival of tumor-bearing mice, promotes T-cell
      cytotoxicity in in vitro cultures of human ccRCC tumors, and augments the
      therapeutic benefits of anti-PD-1 antibodies. Mechanistically, glutamine
      consumption by ccRCC tumor cells results in the local deprivation of
      extracellular glutamine, which induces IL-23 secretion by tumor-infiltrating
      macrophages via the activation of hypoxia-inducible factor 1alpha (HIF1alpha). IL
      23 activates regulatory T-cell proliferation and promotes IL-10 and transforming
      growth factor beta expression, thereby suppressing tumor cell killing by
      cytotoxic lymphocytes. The positive correlations between glutamine metabolism, IL
      23 levels, and Treg responses are confirmed in both TCGA cohort and tumors from
      Shanghai ccRCC patients. Study limitations include the unclear impacts of
      glutamine deprivation and IL-23 on other immune cells. CONCLUSIONS: Macrophage
      secreted IL-23 enhanced Treg functions in glutamine-addicted tumors; thus, IL-23
      is a promising target for immunotherapy in ccRCC. PATIENT SUMMARY: In this study,
      we analyzed the immune components in glutamine-addicted clear cell renal cell
      carcinoma (ccRCC) tumors from two patient cohorts and conducted both in vitro and
      in vivo studies. We found that ccRCC tumor cell-intrinsic glutamine metabolism
      orchestrates immune evasion via interleukin (IL)-23, and IL-23-high patients had
      significantly poorer survival than IL-23-low patients. IL-23 should thus be
      considered a therapeutic target in ccRCC, either alone or in combination with
      immune checkpoint inhibitors.

PMID- 30293905
TI  - Efficacy of Radium-223 in Bone-metastatic Castration-resistant Prostate Cancer
      with and Without Homologous Repair Gene Defects.
AB  - BACKGROUND: Pathogenic mutations in genes mediating homologous recombination (HR)
      DNA repair are present in 20-30% of men with metastatic castrate-resistant
      prostate cancer (mCRPC). Radium-223 is a bone-seeking alpha-emitter that induces
      double-strand DNA breaks, thereby killing cancer cells in the bone
      microenvironment. OBJECTIVE: To evaluate the potential impact of germline or
      somatic HR-deficiency (HRD) mutations on radium-223 efficacy in mCRPC with bone
      metastasis. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective single
      institution study. Medical records of 190 mCRPC patients for whom germline and/or
      somatic DNA sequencing data were available were reviewed. Of these patients, 28
      had received standard-of-care radium-223 at Johns Hopkins between February 2013
      and February 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Alkaline
      phosphatase (ALP) responses and time-to-ALP-progression were the coprimary
      endpoints. Prostate-specific antigen (PSA) responses, overall survival (OS), and
      time to next systemic therapy were also evaluated. RESULTS AND LIMITATIONS: Of
      the 28 patients included, 10 men (35.7%) had a germline/somatic HRD mutation
      (three in BRCA2, and one each in ATM, ATR, CHEK2, FANCG, FANCI, FANCL, and PALB2)
      and 18 (64.3%) did not. Men with HRD mutations (HRD+) had numerically lower ages
      (66 vs 73yr, p=0.25), more soft-tissue metastases (50% vs 38%, p=0.43), and
      higher baseline ALP levels (130 vs 108 U/l, p=0.84). Compared with HRD(-) men,
      HRD(+) patients showed greater ALP responses (80% vs 39%, p=0.04), longer time to
      ALP progression (median10.4 vs 5.8mo, hazard ratio [HR] 6.4, p=0.005), and a
      trend toward longer OS (median 36.9 vs 19.0mo, HR 3.3, p=0.11). PSA responses (0%
      vs 0%, p>0.99) and time to next systemic therapy (HR 1.5, p=0.39) were similar
      between the two groups. Results are limited by the retrospective nature of the
      analysis and the small sample size. CONCLUSIONS: In this exploratory study, bone
      metastatic CRPC patients with inactivating HRD mutations demonstrated
      significantly improved ALP responses and time to ALP progression. These results
      should motivate prospective validation of the "synthetic lethality" hypothesis
      between HRD mutations and radium-223 activity. PATIENT SUMMARY: In this report,
      we retrospectively examined outcomes to metastatic prostate cancer in patients
      with and without DNA repair mutations who received radium-223, a therapy that
      kills cancer cells by causing direct DNA damage. Our study suggested that
      patients who have inherited or acquired DNA repair gene mutations derived greater
      benefit from radium-223 when compared with patients without these mutations. We
      concluded that radium-223 might have an important role in this setting; however,
      prospective studies are needed to confirm whether DNA repair mutations truly make
      radium-223 work better or not.

PMID- 30293906
TI  - Systematic Review of Combination Drug Therapy for Non-neurogenic Lower Urinary
      Tract Symptoms.
AB  - CONTEXT: Several drugs are approved and available for the treatment of lower
      urinary tract symptoms (LUTS) in men and women. However, the vast majority of
      available data, upon which the approval and recommendation in guidelines are
      based, considered only the role of the monotherapies and did not evaluate
      possible combination therapies. OBJECTIVE: This systematic review analyzes the
      efficacy and adverse events of combination therapies for male and female LUTS.
      EVIDENCE ACQUISITION: A systematic literature search in the PubMed/Medline, Web
      of Science, and Cochrane databases was performed according to the Preferred
      Reporting Items for Systematic Reviews and Meta-analysis statement to identify
      clinical trials, randomized controlled trials, meta-analyses, and guidelines on
      male and female LUTS combination therapy published from March 2012 to December
      2017 for men (in order to update a previous men-focused work) and from January
      1988 to December 2017 for women. A total of 58 papers were identified. EVIDENCE
      SYNTHESIS: The most studied combination therapy for the treatment of male LUTS is
      the alpha1-adrenoceptor antagonist/5alpha-reductase inhibitor combination. This
      combination seems to be more efficacious in terms of several outcome variables,
      in particular in men who have moderate-to-severe LUTS and are at risk of disease
      progression. Also in terms of nocturia improvements, this combination is
      significantly more effective than the monotherapy. The other often studied
      combination treatment, in both male and female patients with LUTS, was the
      combination of antimuscarinics (in particular solifenacin) and mirabegron. This
      combination seems to be more effective in comparison with the monotherapies with
      respect to urinary incontinence and urgency urinary incontinence episodes and
      several other objective and subjective parameters, without relevant increase of
      adverse events. The combination of hormone therapy and antimuscarinics in women
      with LUTS does not seem to be useful. CONCLUSIONS: For the treatment of LUTS in
      men and women, combination therapy appears to be a promising option to optimize
      the efficacy of the available drugs for those who do not experience sufficient
      benefit with monotherapy. This add-on scenario offers the possibility to have a
      more tailored approach to the management of LUTS, always seeking the optimal
      balance between efficacy and tolerability for a given patient. PATIENT SUMMARY:
      Some combination of drugs may offer advantages over monotherapies for the
      treatment of voiding and storage complaints in men and women.

PMID- 30293907
TI  - Was it All Useless?

PMID- 30293908
TI  - External Beam Radiotherapy Increases the Risk of Bladder Cancer When Compared
      with Radical Prostatectomy in Patients Affected by Prostate Cancer: A Population
      based Analysis.
AB  - BACKGROUND: Long-term survival can be achieved in patients affected by localized
      prostate cancer (PCa) treated with either radical prostatectomy (RP) or external
      beam radiotherapy (EBRT). However, development of a second primary tumor is still
      poorly investigated. OBJECTIVE: To investigate the impact of RP and EBRT on
      subsequent risk of developing bladder (BCa) and/or rectal cancer (RCa) among PCa
      survivors. DESIGN, SETTING, AND PARTICIPANTS: A total of 84397 patients diagnosed
      with localized PCa, treated with RP or EBRT between 1988 and 2009, and older than
      65 yr of age were identified in the Surveillance, Epidemiology, and End Results
      Medicare insurance program-linked database. Our primary objective was to
      investigate the effect of EBRT and RP on the second primary BCa and RCa
      incidence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable competing
      risk regression analyses were performed to assess the risk of developing a second
      primary BCa or RCa. RESULTS AND LIMITATIONS: Of the 84397 individuals included in
      the study, 33252 (39%) were treated with RP and 51145 (61%) with EBRT. Median
      follow-up was 69 months, and follow-up periods for patients who did not develop
      BCa, RCa, or pelvic cancer were 68, 69, and 68 mo, respectively. A total of 1660
      individuals developed pelvic tumors (1236 BCa and 432 RCa). The 5- and 10-yr
      cumulative BCa incidence rates were 0.75% (95% confidence interval [CI]: 0.64
      0.85%) and 1.63% (95% CI: 1.45-1.80%) versus 1.26% (95% CI: 1.15-1.37%) and 2.34%
      (95% CI: 2.16-2.53%) for patients treated with RP versus EBRT, respectively. The
      5- and 10-yr cumulative RCa incidence rates were 0.32% (95% CI: 0.25-0.39%) and
      0.73% (95% CI: 0.61-0.85%) versus 0.36% (95% CI: 0.30-0.41%) and 0.69% (95% CI:
      0.60-0.79%) for patients treated with RP versus EBRT, respectively. On
      multivariable competing risk regression analyses, treatment with EBRT was
      independently associated with the risk of developing a second primary BCa (hazard
      ratio: 1.35, CI: 1.18-1.55; p<0.001), but not RCa (p=0.4). Limitations include
      lack of information regarding the dose of radiotherapy and the retrospective
      nature with the implicit risk of selection bias. CONCLUSIONS: Patients treated
      with EBRT are at increased risk of developing a second primary BCa compared with
      those treated with RP. However, no differences were found considering RCa
      incidence in patients treated with RP or EBRT within the first 5 yr after primary
      therapy. These results need to be validated in a well-designed randomized
      prospective trial. PATIENT SUMMARY: We retrospectively analyzed the risk of
      developing a second primary bladder or rectal cancer during follow-up for
      patients treated with radical prostatectomy or external beam radiotherapy for a
      localized prostate cancer. We found that those treated with external beam
      radiotherapy are at an increased risk of developing a second primary bladder
      cancer tumor.

PMID- 30293909
TI  - Effects of vitamin D supplementation on musculoskeletal health: a systematic
      review, meta-analysis, and trial sequential analysis.
AB  - BACKGROUND: The effects of vitamin D on fractures, falls, and bone mineral
      density are uncertain, particularly for high vitamin D doses. We aimed to
      determine the effect of vitamin D supplementation on fractures, falls, and bone
      density. METHODS: In this systematic review, random-effects meta-analysis, and
      trial sequential analysis, we used findings from literature searches in
      previously published meta-analyses. We updated these findings by searching
      PubMed, Embase, and Cochrane Central on Sept 14, 2017, and Feb 26, 2018, using
      the search term "vitamin D" and additional keywords, without any language
      restrictions. We assessed randomised controlled trials of adults (>18 years) that
      compared vitamin D with untreated controls, placebo, or lower-dose vitamin D
      supplements. Trials with multiple interventions (eg, co-administered calcium and
      vitamin D) were eligible if the study groups differed only by use of vitamin D.
      We excluded trials of hydroxylated vitamin D analogues. Eligible studies included
      outcome data for total or hip fractures, falls, or bone mineral density measured
      at the lumbar spine, total hip, femoral neck, total body, or forearm. We
      extracted data about participant characteristics, study design, interventions,
      outcomes, funding sources, and conflicts of interest. The co-primary endpoints
      were participants with at least one fracture, at least one hip fracture, or at
      least one fall; we compared data for fractures and falls using relative risks
      with an intention-to-treat analysis using all available data. The secondary
      endpoints were the percentage change in bone mineral density from baseline at
      lumbar spine, total hip, femoral neck, total body, and forearm. FINDINGS: We
      identified 81 randomised controlled trials (n=53 537 participants) that reported
      fracture (n=42), falls (n=37), or bone mineral density (n=41). In pooled
      analyses, vitamin D had no effect on total fracture (36 trials; n=44 790,
      relative risk 1.00, 95% CI 0.93-1.07), hip fracture (20 trials; n=36 655, 1.11,
      0.97-1.26), or falls (37 trials; n=34 144, 0.97, 0.93-1.02). Results were similar
      in randomised controlled trials of high-dose versus low-dose vitamin D and in
      subgroup analyses of randomised controlled trials using doses greater than 800 IU
      per day. In pooled analyses, there were no clinically relevant between-group
      differences in bone mineral density at any site (range -0.16% to 0.76% over 1-5
      years). For total fracture and falls, the effect estimate lay within the futility
      boundary for relative risks of 15%, 10%, 7.5%, and 5% (total fracture only),
      suggesting that vitamin D supplementation does not reduce fractures or falls by
      these amounts. For hip fracture, at a 15% relative risk, the effect estimate lay
      between the futility boundary and the inferior boundary, meaning there is
      reliable evidence that vitamin D supplementation does not reduce hip fractures by
      this amount, but uncertainty remains as to whether it might increase hip
      fractures. The effect estimate lay within the futility boundary at thresholds of
      0.5% for total hip, forearm, and total body bone mineral density, and 1.0% for
      lumbar spine and femoral neck, providing reliable evidence that vitamin D does
      not alter these outcomes by these amounts. INTERPRETATION: Our findings suggest
      that vitamin D supplementation does not prevent fractures or falls, or have
      clinically meaningful effects on bone mineral density. There were no differences
      between the effects of higher and lower doses of vitamin D. There is little
      justification to use vitamin D supplements to maintain or improve musculoskeletal
      health. This conclusion should be reflected in clinical guidelines. FUNDING:
      Health Research Council of New Zealand.

PMID- 30293910
TI  - Vitamin D and bone density, fractures, and falls: the end of the story?

PMID- 30293911
TI  - Neu3CA-RT: A framework for real-time fMRI analysis.
AB  - Real-time functional magnetic resonance imaging (rtfMRI) allows visualisation of
      ongoing brain activity of the subject in the scanner. Denoising algorithms aim to
      rid acquired data of confounding effects, enhancing the blood oxygenation level
      dependent (BOLD) signal. Further image processing and analysis methods, like
      general linear models (GLM) or multivariate analysis, then present application
      specific information to the researcher. These processes are typically applied to
      regions of interest but, increasingly, rtfMRI techniques extract and classify
      whole brain functional networks and dynamics as correlates for brain states or
      behaviour, particularly in neuropsychiatric and neurocognitive disorders. We
      present Neu3CA-RT: a Matlab-based rtfMRI analysis framework aiming to advance
      scientific knowledge on real-time cognitive brain activity and to promote its
      translation into clinical practice. Design considerations are listed based on
      reviewing existing rtfMRI approaches. The toolbox integrates established SPM
      preprocessing routines, real-time GLM mapping of fMRI data to a basis set of
      spatial brain networks, correlation of activity with 50 behavioural profiles from
      the BrainMap database, and an intuitive user interface. The toolbox is
      demonstrated in a task-based experiment where a subject executes visual, auditory
      and motor tasks inside a scanner. In three out of four experiments, resulting
      behavioural profiles agreed with the expected brain state.

PMID- 30293912
TI  - [Clinical and pathological profile of the pleural malignant mesothelioma: A
      retrospective study about 30 cases].
AB  - BACKGROUND: The malignant pleural mesothelioma (MPM) is a rare tumour usually
      associated to asbestos exposure. The delay between the exposure and the
      occurrence of the cancer can reach 40 years. This caused the pick of incidence
      described in many countries including Tunisia. The diagnosis is suspected based
      on clinical features but positive diagnosis is microscopic. Our aim was to
      describe the clinical and microscopic features of MPM through a single
      institution experience. PATIENTS AND METHODS: We conducted a retrospective study
      about 30 MPM diagnosed over a 20-year-period (1995-2015). We included only
      patients with complete records including clinical, radiologic and microscopic
      features. All the microscopic diagnoses were reviewed by 2 pathologists. A mean
      of 12 slides per case was reviewed. The diagnosis was based on the 2015 WHO
      classification. RESULTS: The mean age of the patients was 61 years, average 22 to
      80 years. The sex ratio was 6,5. An asbetose exposition was reported in 21 cases.
      The most frequent symptoms was chest pain reported in 25 cases. Physical exam was
      normal in 9 cases. It revealed pleural syndorm in most patients (60 %). Imaging
      findings consisted mainly in diffuse pleural thickening in 17 cases. Twelve
      tumours were classified as stage I, 3 stage II, 14 stage III et 1 stage IV.
      Pleural biopsy was performed using needle in 18 cases, through thoracoscopy in 16
      cases, thoracotomy in 3 cases and allowed the diagnosis in respectively 7
      cases/18, 16 cases/16 and 3 cases/3. A lymph node biopsy was performed through
      mediastinoscopy in one case and yelded the diagnosis. The diagnosis was performed
      on surgical specimen in 2 patients: one bullectomy and one right upper lobectomy.
      The microscopic exam concluded to an EM in 17 cases, sarcomatoid mesothelioma
      (SM) in 4 cases and biphasic mesothelioma (BM) in 9 cases. Pan-cytokeratin
      antibody was used in all cases in association with 2 antibodies with positive
      diagnostic value and 2 antibodies with negative diagnostic value. It was repeated
      in 15 cases and the most used antibodies were the anti-calretinin and the TTF1.
      This was due to the lack of fixation in one case and in order to reach a quality
      criteria in the other cases. Surgical resection was possible in 2 patients. 15
      patients were lost of view after a mean follow-up period of 3 months. Thirteen
      patients died before or during the follow-up. CONCLUSION: This work was about a
      Tunisian experience in the diagnosis and management of MPM. The major limits
      faced were the incomplete databases, the small number of patients included.
      Microsocpic positive diagnosis necessitates a degree of expertise and every
      laboratory has to determine the most valuable antibodies through its experience
      in order to optimize the diagnosis and to reduce the delay of diagnosis.

PMID- 30293913
TI  - Management of acute severe ulcerative colitis in Spain: A nationwide clinical
      practice survey.
AB  - INTRODUCTION: Ulcerative colitis (UC) is a chronic disease of the digestive tract
      and up to 20-30% of UC patients may suffer a severe flare-up during the course of
      the disease. Although there are national and international recommendations about
      its clinical management, there is not enough information about the treatment of
      acute severe UC in clinical practice. METHODS: An electronic and anonymous survey
      with 51 multiple-choice questions was performed among all the members of the
      Spanish Crohn's Disease and Ulcerative Colitis Working Group (GETECCU). RESULTS:
      Out of the 164 responders (20%), most were gastroenterologists (95%), with 59%
      from tertiary hospitals treating a median of 5 patients per year (IQR: 3-8) with
      a severe flare-up of ulcerative colitis. An endoscopic examination was routinely
      performed in 86% of patients (62% at admission). The most commonly used
      corticosteroid was methylprednisolone, usually at a dose of 60mg/day, and its
      response was assessed after a median of 3days (IQR: 3-5). Both in thiopurine
      naive and thiopurine-refractory patients, infliximab was the drug most frequently
      prescribed as rescue therapy. Half of responders (55%) had ever prescribed a
      first dose of infliximab higher than 5 mg/kg, and a higher proportion (73%) had
      ever prescribed an earlier dose of infliximab in the second or third infusion.
      CONCLUSIONS: Acute severe UC is generally managed according to current treatment
      guidelines in our setting. The rescue therapy most commonly prescribed is
      infliximab, and the use of intensified or accelerated regimens with this
      biological drug is not unusual.

PMID- 30293914
TI  - Elimination of hepatitis C virus infection from a hemodialysis unit and impact of
      treatment on the control of anemia.
AB  - INTRODUCTION: In the interferon era, the treatment of hepatitis C virus (HCV)
      infection in patients on haemodialysis (HD) was limited due to the significant
      number of treatment-related adverse events (AEs). Direct-acting antivirals (DAAs)
      have demonstrated their efficacy and safety in the treatment of HCV in patients
      with advanced chronic kidney disease on haemodialysis. The objective of the study
      was to evaluate the success in eliminating HCV infection from our dialysis unit
      using DAAs, and to assess the impact of HCV elimination on clinical and
      analytical outcomes. PATIENTS AND METHODS: This is a prospective, interventional,
      single-center study at Hospital Clinic de Barcelona. All HCV-RNA positive
      patients who received antiviral therapy with DAAs within a 3-year period (2014
      2017) were analyzed (n=20). Data on virologic response, adverse events, and
      biochemical and hematological parameters during and after DAA therapy were
      analyzed. RESULTS: All patients achieved sustained virologic response (SVR) and
      only 40% of patients presented with mild AEs. None of the patients presented with
      HCV reinfection after a 1-year follow-up period, and thus HCV was eliminated from
      our HD unit. SVR was associated with a significant increase in hemoglobin and
      hematocrit, and a tendency toward the need for lower doses of iron
      supplementation with no changes in darbepoetin dose. CONCLUSION: HCV infection
      can be safely eliminated from HD units with the use of DAAs, preventing new
      infections in patients and healthcare staff. In the short term, the achievement
      of SVR is associated with an improvement in the control of anemia.

PMID- 30293915
TI  - Targeted sequencing and molecular profiling of a papillary and cribriform clear
      cell intrahepatic cholangiocarcinoma reveals absence of selectable mutations.

PMID- 30293916
TI  - Dr. Hyacinthe Guilleminot and the first respiratory and cardiac synchronisation
      systems for obtaining radiological images.
AB  - In an era when it was not possible to achieve quality x-rays with short exposure
      times, the need to obtain chest images without movement led the French doctor
      Emre Hyacinthe Guilleminot to construct a machine that repeatedly emitted x-rays
      only when desired during the respiratory cycle. His aim was to create a
      satisfactory radiograph from multiple short bursts performed at the moment of
      inhalation or exhalation, based on Charles Bouchard's research on heart disease.
      He extended his idea to radiography of the heart, creating a system that enabled
      images to be obtained disassociating the phases of heartbeat. This article seeks
      to explain the basic functioning of these mechanisms, and to recover previous
      research papers that led to their creation. We will also retrieve biographical
      and personal data of the two people involved - one directly, the other indirectly
      - in these novel inventions.

PMID- 30293917
TI  - Successful resuscitation from cardiac arrest due to histologically revealed tumor
      embolism following bilateral intramedullary nailing of metastatic femoral
      lesions.

PMID- 30293918
TI  - Two-stage revision using antifungal-loaded cement beads for the treatment of
      Candida infection following revision total hip arthroplasty: A case report.

PMID- 30293919
TI  - The balance of sleep: Role of the vestibular sensory system.
AB  - The vestibular system encodes linear and angular head motion supporting numerous
      functions from gaze stabilization and postural control, to high-level cortical
      functions involving spatial cognition, including self-body perception,
      verticality perception, orientation, navigation and spatial memory. At the
      brainstem and mesencephalic levels, the vestibular organs also influence postural
      blood pressure regulation, bone density and muscle composition via specific
      vestibulo-sympathetic efferences and have been shown to act as a powerful
      synchronizer of circadian rhythms. Here, we review the evidence that sleep
      deprivation and sleep apnea syndrome alter vestibular-related oculo-motor and
      postural control, and that, in turn, vestibular pathologies induce sleep
      disturbances. We suggest that sleep-related neuroplasticity might serve the
      adaptation and compensation processes following vestibular lesions in patients.
      Interestingly, a reciprocal neuroanatomical route between the vestibular nuclei
      and the orexinergic neurons has been reported. While orexinergic modulation of
      the vestibular nuclei related to postural control has been suggested, we
      postulate that vestibular inputs might in turn influence the sleep-wake state
      switch, informing the brain about the daily quantity of motion.

PMID- 30293920
TI  - Methods of gestational age assessment influence the observed association between
      antiretroviral therapy exposure, preterm delivery, and small-for-gestational age
      infants: a prospective study in Cape Town, South Africa.
AB  - PURPOSE: Heterogeneous findings exist on antiretroviral therapy (ART) use in
      pregnancy and preterm delivery (PTD) or infants born small-for-gestational age
      (SGA). Whether reported differences may be explained by methods used to ascertain
      gestational age (GA) has not been explored. METHODS: We enrolled consecutive
      pregnant women attending a large primary care antenatal clinic in South Africa.
      Public-sector midwives assessed GA by last menstrual period (LMP) and symphysis
      fundal height (SFH). Separately, if clinical GA was less than 24 weeks,
      ultrasound (US) was performed by a research sonographer blinded to midwife
      assessments. In analysis, the impact of measurement error on the association
      between HIV/ART status and birth outcome by GA method was assessed, and factors
      associated with clinical GA underestimation or overestimation identified.
      RESULTS: In 1787 women included overall, estimated PTD incidence was 36% by LMP,
      17% by SFH, and 11% by US. PTD risk was higher for HIV-infected than HIV
      uninfected women using US-GA (adjusted odds ratio [aOR] 1.95; 95% CI 1.10-3.46);
      for LMP/SFH-GA, the associations were smaller and not significant. These findings
      persisted after adjustment for age, parity, height, and previous PTD. PTD risk
      did not vary by timing of ART initiation (before or during pregnancy) for any
      method. Elevated BMI and older age were associated with decreased risk of
      underestimation by both LMP and SFH; HIV status and obesity were associated with
      increased risk of overestimation by SFH. There were no differences in SGA
      incidence across GA methods. CONCLUSIONS: Findings for an association between
      HIV/ART and birth outcomes are substantially influenced by GA assessment method.
      With growing public health interest in this association, future research efforts
      should seek to standardize optimal measures of gestation.

PMID- 30293921
TI  - In situ bioremediation of 1,2-dibromoethane (EDB) in groundwater to part-per
      trillion concentrations using cometabolism.
AB  - 1,2-Dibromoethane (ethylene dibromide; EDB) is a probable human carcinogen that
      was historically added to leaded gasoline as a scavenger to prevent the build-up
      of lead oxide deposits in engines. Studies indicate that EDB is present at
      thousands of past fuel spill sites above its stringent EPA Maximum Contaminant
      Level (MCL) of 0.05 MUg/L. There are currently no proven in situ options to
      enhance EDB degradation in groundwater to meet this requirement. Based on
      successful laboratory studies showing that ethane can be used as a primary
      substrate to stimulate the aerobic, cometabolic biodegradation of EDB to <0.015
      MUg/L (Hatzinger et al., 2015), a groundwater recirculation system was installed
      at the FS-12 EDB plume on Joint Base Cape Cod (JBCC), MA to facilitate in situ
      treatment. Groundwater was taken from an existing extraction well, amended with
      ethane, oxygen, and inorganic nutrients and then recharged into the aquifer
      upgradient of the extraction well creating an in situ reactive zone. The
      concentrations of EDB, ethane, oxygen, and anions in groundwater were measured
      with time in a series of nested monitoring wells installed between the extraction
      and injection well. EDB concentrations in the six monitoring wells that were
      hydraulically well-connected to the pumping system declined from ~ 0.3 MUg/L (the
      average concentration in the recirculation cell after 3 months of operation
      without amendment addition) to <0.02 MUg/L during the 4-month amendment period,
      meeting both the federal MCL and the more stringent Massachusetts MCL (0.02
      MUg/L). The data indicate that cometabolic treatment is a promising in situ
      technology for EDB, and that low regulatory levels can be achieved with this
      biological approach.

PMID- 30293922
TI  - Solitary Mucinous Prostate Adenocarcinoma Lung Metastasis Detected by 68Ga-PSMA
      11 PET/CT.

PMID- 30293923
TI  - Quality of Life in Long-Term Testicular Cancer Survivors With Compensated Leydig
      Cell Dysfunction.
AB  - BACKGROUND: Compensated Leydig cell (LC) dysfunction, defined by elevated serum
      levels of luteinizing hormone (LH) in combination with normal total testosterone
      levels, is common in testicular cancer (TC) survivors. The association between
      this condition and quality of life is unknown. We aimed to clarify if TC
      survivors with compensated LC dysfunction have impaired quality of life. PATIENTS
      AND METHODS: In total, 147 long-term TC survivors were included. On the basis of
      a single measurement of testosterone and LH, compensated LC dysfunction was
      defined by age-adjusted levels of LH above normal range combined with
      testosterone levels within the normal range. Quality-of-life outcomes including
      sexual function, anxiety and depression, fatigue, and overall self-evaluated
      quality of life were compared between patients with and without compensated LC
      dysfunction with adjustment for age. RESULTS: In total, 60 TC survivors had
      compensated LC dysfunction and 87 TC survivors had normal LC function. TC
      survivors with compensated LC dysfunction had lower serum levels of total
      testosterone (11 vs. 13 nmol/L, P = .016). There were no significant differences
      in the investigated quality-of-life outcomes (anxiety, depression, sexual
      function, fatigue) between the 2 groups. CONCLUSION: Compensated LC dysfunction
      in TC survivors was not associated with symptoms of depression, anxiety, sexual
      dysfunction, fatigue, or impaired overall self-evaluated quality of life.
      Limitations include the few cases of symptoms of depression (n = 7). Our findings
      do not suggest that testosterone substitution is indicated in TC survivors with
      compensated LC dysfunction.

PMID- 30293924
TI  - The C-Reactive Protein to Albumin Ratio Predicts Acute Kidney Injury in Patients
      With ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous
      Coronary Intervention.
AB  - BACKGROUND: The relationship between acute kidney injury (AKI) and C-reactive
      protein (CRP) and albumin has been previously demonstrated in patients with ST
      elevation myocardial infarction (STEMI) treated with primary percutaneous
      coronary intervention (pPCI). However, to our knowledge, CRP to albumin ratio
      (CAR), a newly introduced inflammation-based risk score, has not yet been
      studied. In this study, we aimed to investigate the possible relationship between
      the CAR and AKI. METHOD: A total of 815 consecutive STEMI patients treated with
      pPCI were reviewed. RESULTS: 110 (13.5%) patients developed AKI in the study
      population. The subjects were divided into two groups according to AKI
      development. The in-hospital mortality rate was higher in patients with AKI than
      those without AKI (15.5% vs. 1.3%; p<0.001). The patients with AKI had
      significantly higher mean value of CRP and CAR (0.29 [0.16-0.50] vs. 0.55 [0.37
      1.05]; p<0.001) and lower mean levels of albumin than those without AKI. Age,
      diabetes mellitus, haematocrit, left ventricular ejection fraction, hypotension,
      and CAR (Odd's ratio [OR]2.307, 95% confidence interval [CI] 1.397-3.809,
      p=0.001) were independent predictors of AKI. CONCLUSION: The CAR may be a useful
      inflammation-based risk score to predict AKI development in STEMI patients
      treated with pPCI.

PMID- 30293925
TI  - Concurrent Campylobacter jejuni bacteremia and intussusception in an
      immunocompetent five-year-old child.
AB  - Bacterial enteritis has been reported to be a risk factor for childhood
      intussusception. However, no case report concerning children with concurrent
      Campylobactor bacteremia and intussusception were found in the literature.
      Herein, we report a 5-year-old male preschool child who presented symptoms of
      infectious diarrhea, and ileocecal type intussuscepton and Campylobactor jejuni
      bacteremia were found after a series of investigations.

PMID- 30293926
TI  - Monitoring early developed low bone mineral density in HIV-infected patients by
      intact parathyroid hormone and circulating fibroblast growth factor 23.
AB  - BACKGROUND/PURPOSE: HIV-infected patients have a high prevalence of low bone
      mineral density (BMD), but BMD changes remain unclear. This cross-sectional
      retrospective observational study aimed to characterize the prevalence and
      associated factors of low BMD in HIV patients. METHODS: Between 1 January 2015
      and 31 December 2016, all patients aged 20 years or greater who sought for HIV
      care were included. BMD was measured by dual-energy X-ray absorptiometry.
      Multivariable analyses of the association with HIV disease status, treatment and
      anthropometric parameters were performed. Circulating fibroblast growth factor 23
      and intact parathyroid hormone were measured. RESULTS: A total of 137 patients
      was included; their median age was 39 years old; 97.8% were treated with
      combination antiretroviral therapy (cART); Body mass index (BMI) was 21.97 kg/m2.
      Sixty-one patients (44.5%) showed low BMD (osteopenia and osteoporosis) based on
      the WHO criteria. The median BMD was -0.80 g/cm2 (IQR, -1.5 to -0.2). The
      prevalence rate of low BMD was 37% in those who were aged 20-29 years, 45.2% in
      those who were aged 30-39 years, 45.2% in those who were aged 40-49 years, 45.8%
      in those who were aged 50-59 years, and 53.8% in those who were aged ?60 years.
      More than half of patients (50.4%, 69/137) were younger than 40 years. Compared
      with normal BMD group, the low BMD group has a higher proportion of secondary
      hyperparathyroidism (18.0% vs 5.3%, p: 0.026) and a lower median C-terminal FGF23
      level (48.92 vs 62.61 pg/ml, p: 0.008). Univariate and multivariate analyses of
      the factors associated with low BMD. We found that only serum intact-parathyroid
      hormone (iPTH) > 69 pg/ml (OR, 3.86; 95% CI, 1.14-13.09) was statistically
      significant associated with low BMD in multivariate analysis. CONCLUSIONS: This
      cohort-based survey showed a high prevalence of low BMD among HIV-infected adults
      which included young-age patient in an university hospital. Secondary
      hyperparathyroidism was significantly associated with low BMD. There was no
      association between FGF23 and low BMD.

PMID- 30293927
TI  - Outcome and prognostic factors of patients treated in the intensive care unit for
      carbon monoxide poisoning.
AB  - BACKGROUND: Carbon monoxide (CO), a colorless and odorless gas, is one of the
      common causes of poisoning-related deaths worldwide. CO poisoning can result in
      hypoxic brain damage and death, but intensive care can improve the likely outcome
      for critically ill patients. However, there is a paucity of clinical data
      regarding the prognostic factors and association between organ dysfunction and
      clinical outcome of patients treated for CO poisoning in the intensive care unit
      (ICU). METHODS: We performed a retrospective study of patients admitted to a
      university affiliated hospital ICU between July 2001 and December 2010 following
      CO poisoning. Outcomes were survival to ICU discharge and to hospital discharge.
      RESULTS: Seven hundred and eighty-seven patients were admitted to the university
      hospital following CO poisoning, of which 140 (17.8%) were admitted to the
      hospital ICU. The overall mortality rate of the patients admitted to the ICU was
      14.3% (20/140). Univariate analysis indicated that non-surviving patients with CO
      poisoning were more likely to have initial blood carboxyhemoglobin (COHb) level >
      30%, shock, acute respiratory failure, Acute Physiology and Chronic Health
      Evaluation II (APACHE II) score >= 25, Glasgow coma scale (GCS) score of 3, acute
      renal failure, dysfunction or failure of more than 3 organs, low blood pH, low
      HCO3- level, high potassium level, and high glucose level. They were also more
      likely to have not received hyperbaric oxygen (HBO) intervention. Multivariate
      logistical regression analysis indicated that the mortality rate of patients
      treated in the ICU for CO poisoning was higher if their initial APACHE II score
      was >=25, GCS was 3, and more than 3 organs were dysfunctional. Moreover, HBO
      intervention in ICU significantly decreased patients' risk of mortality due to CO
      poisoning. CONCLUSION: In conclusion, we observed that APACHE II score >25, GCS
      3, and dysfunction of more than 3 organ systems on admission to emergency
      department was associated with a significant mortality risk in patients treated
      in the ICU for CO poisoning. Moreover, HBO therapy could reduce the risk of
      mortality in patients with CO poisoning in ICU.

PMID- 30293928
TI  - Early percutaneous cholecystostomy versus antibiotic treatment for mild and
      moderate acute cholecystitis: A retrospective cohort study.
AB  - BACKGROUND: Percutaneous cholecystostomy (PC) is an effective treatment for
      severe acute cholecystitis (AC). Guidelines recommend PC as rescue therapy for
      patients with mild or moderate AC who do not receive emergent cholecystectomy.
      This study aims to investigate whether PC could be a first-line treatment for
      these patients. METHODS: Adult patients admitted through the emergency department
      between October 2004 and December 2013 were retrospectively reviewed. Patients
      with mild or moderate AC who did not undergo emergent cholecystectomy were
      included. Early PC was defined as a PC tube inserted within 24 h of diagnosis.
      The outcomes were compared between patients who received antibiotics plus early
      PC (early PC group) and those who received antibiotic treatment alone (antibiotic
      group). RESULTS: A total of 698 patients were included. The mean age was 63.4
      years. There were 171 patients in the early PC group and 527 patients in the
      antibiotic group. Multivariable logistic regression analyses indicated that early
      PC was significantly associated with a decreased rate of prolonged fever (odds
      ratio [OR], 0.31; 95% confidence interval [CI], 0.16-0.57; p < 0.001). Early PC
      also correlated with both increased short-term (OR, 15.95; 95% CI, 5.73-44.38; p
      < 0.001) and long-term treatment success (OR, 4.27; 95% CI, 2.55-7.15; p <
      0.001). CONCLUSION: For patients with mild/moderate AC without emergent
      cholecystectomy, early PC might expedite sepsis resolution and improve the
      treatment success rate compared with antibiotic treatment alone. This result
      should be deemed as hypothesis-generating and should be examined in a randomized
      controlled trial.

PMID- 30293929
TI  - Short-term heart rate variability as a predictor of long-term survival in
      patients with chronic hemodialysis: A prospective cohort study.
AB  - BACKGROUND: Heart rate variability (HRV), a non-invasive measurement of the
      sympathetic-vagal balance, has been demonstrated as a predictor of long-term
      survival in various patient populations. However, its predictive value in
      patients with end-stage renal disease (ESRD) has not been evaluated in a long
      term follow-up study. METHODS: Prospective data collected for 41 patients with
      chronic hemodialysis (age 59 +/- 10 years, men 51.3%, diabetes mellitus 31%, and
      duration of dialysis 64 +/- 50 months) who underwent a 5-minute electrocardiogram
      (ECG) recording as a baseline for frequency domain HRV analysis. RESULTS: During
      a median follow-up of 150.2 months from 2003 to 2014, 15 (35.7%) patients died (3
      due to cardiac causes and 12 due to non-cardiac causes). The Cox proportional
      hazards model suggested that the low frequency versus high frequency signal
      (LF/HF) of a high ratio for the HRV and diabetes mellitus were two independent
      predictors of mortality (hazard ratios 3.028 and 3.494; p = 0.033 and 0.022,
      respectively). Less reduction in MAP during dialysis showed borderline
      significance of long-term survival than those with larger drop (p = 0.058).
      CONCLUSION: A short ECG recording and an analysis of the frequency domain of the
      HRV is clinically predictive of the long-term survival of patients with chronic
      hemodialysis.

PMID- 30293930
TI  - Exploring the half-life of glyphosate in human urine samples.
AB  - BACKGROUND: The International Agency for Research on Cancer (IARC) has recently
      classified glyphosate as a Group 2A 'probably carcinogenic to humans'. Due to
      this carcinogenic classification and resulting international debate, there is an
      increased demand for studies evaluating human health effects from glyphosate
      exposures. There is currently limited information on human exposures to
      glyphosate and a paucity of data regarding glyphosate's biological half-life in
      humans. OBJECTIVE: This study aims to estimate the human half-life of glyphosate
      from human urine samples collected from amenity horticulture workers using
      glyphosate based pesticide products. METHODS: Full void urine spot samples were
      collected over a period of approximately 24 h for eight work tasks involving
      seven workers. The elimination time and estimation of the half-life of glyphosate
      using three different measurement metrics: the unadjusted glyphosate
      concentrations, creatinine corrected concentrations and by using Urinary
      Excretion Rates (UER) (MUg L-1, MUmol/mol creatinine and UER MUg L-1) was
      calculated by summary and linear interpolation using regression analysis.
      RESULTS: This study estimates the human biological half-life of glyphosate as
      approximately 5 1/2, 10 and 7 1/4 hours for unadjusted samples, creatinine
      corrected concentrations and by using UER (MUg L-1, MUmol/mol creatinine, UER MUg
      L-1), respectively. The approximated glyphosate half-life calculations seem to
      have less variability when using the UER compared to the other measuring metrics.
      CONCLUSION: This study provides new information on the elimination rate of
      glyphosate and an approximate biological half-life range for humans. This
      information can help optimise the design of sampling strategies, as well as
      assisting in the interpretation of results for human biomonitoring studies
      involving this active ingredient. The data could also contribute to the
      development or refinement of Physiologically Based PharmacoKinetic (PBPK) models
      for glyphosate.

PMID- 30293931
TI  - Safety, tolerability, and effectiveness of oral zonisamide therapy in comparison
      with intramuscular adrenocorticotropic hormone therapy in infants with West
      syndrome.
AB  - West syndrome is a distinct, infantile onset, epileptic encephalopathy,
      associated with poor neurodevelopmental outcome. The present study was designed
      as a randomized, open-label, pilot study to evaluate the safety, feasibility, and
      effectiveness of oral zonisamide therapy in comparison with adrenocorticotropic
      hormone therapy in infants with West syndrome. Thirty infants with West syndrome
      were randomized to receive treatment with either synthetic, intramuscular
      adrenocorticotropic hormone (30-60 IU) or oral zonisamide (4-25 mg/kg/day). The
      study participants had a long treatment lag and preponderance of male sex (90%).
      The primary effectiveness outcome measure was the cessation of epileptic spasms
      at 2 weeks of initiation of therapy and persistent till 6 weeks as per West
      Delphi consensus statement recommendations. Comparison of efficacies of
      zonisamide versus adrenocorticotropic hormone was as following: the cessation of
      epileptic spasms (27% vs. 40%, p = 0.70), resolution of hypsarrhythmia at 14 days
      (20% vs. 33%, p = 0.68) and resolution of hypsarrhythmia at 6 weeks (36% vs. 71%,
      p = 0.14). Overall, the study observed a poor efficacy of both
      adrenocorticotropic hormone and zonisamide therapy, which is probably due to long
      treatment lag and a high proportion of structural aetiology. However, oral
      zonisamide appeared to be safe and tolerable in the study.

PMID- 30293932
TI  - Prediction of lowest nocturnal blood glucose level based on self-monitoring of
      blood glucose in Japanese patients with type 2 diabetes.
AB  - AIMS: Continuous glucose monitoring (CGM) is not available for all patients with
      type 2 diabetes (T2D) at risk of nocturnal hypoglycemia (NH). This study was
      performed to predict the lowest nocturnal blood glucose (LNBG) levels. METHODS:
      An LNBG prediction formula was developed by multivariate analysis using the data
      including self-monitoring of blood glucose from a formula making (FM) group of 29
      insulin-treated T2D patients with CGM. The validity of the formula was assessed
      by nonparametric regression analysis of actual and predicted values in a formula
      validation group consisting of 21 other insulin-treated patients. The clinical
      impact on prediction was evaluated using a Parkes error grid. RESULTS: In the FM
      group with a median age of 64.0, the following formula was established: Predicted
      LNBG (mg/dL) = 127.4-0.836 * Age (y) + 0.119 * Self-monitored fasting blood
      glucose (mg/dL) + 0.717 * Basal insulin dose (U/day) (standard error of
      calibration 17.2 mg/dL). Based on the validation results, standard error of
      prediction was 31.0 mg/dL. All predicted values fell within zones A (no effect on
      clinical action) and B (little or no effect on clinical outcome) on the grid.
      CONCLUSIONS: LNBG could be predicted, and may be helpful for NH prevention.

PMID- 30293933
TI  - Relationship between physicians' death anxiety and medical communication and
      decision-making: A systematic review.
AB  - OBJECTIVE: To examine the relationship between physicians' death anxiety and
      medical communication and decision-making. It was hypothesized that physicians'
      death anxiety may lead to the avoidance of end-of-life conversations and a
      preference for life-prolonging treatments. METHODS: PubMed and PsycInfo were
      systematically searched for empirical studies on the relation between physicians'
      death anxiety and medical communication and decision-making. RESULTS: This review
      included five quantitative and two qualitative studies (N = 7). Over 38 relations
      between death anxiety and communication were investigated, five were in line with
      and one contradicted our hypothesis. Physicians' death anxiety seemes to make end
      of-life communication more difficult. Over 40 relations between death anxiety and
      decision-making were investigated, three were in line with and two contradicted
      the hypothesis. Death anxiety seemes related to physicians' guilt or doubt after
      a patient's death. CONCLUSIONS: There was insufficient evidence to confirm that
      death anxiety is related to more avoidant communication or decision-making.
      However, death anxiety does seem to make end-of-life communication and decision
      making more difficult for physicians. PRACTICE IMPLICATIONS: Education focused on
      death and dying and physicians' emotions in medical practice may improve the
      perceived ease with which physicians care for patients at the end of life.

PMID- 30293934
TI  - Sociodemographic and clinical correlates of key outcomes from a Mobile Insulin
      Titration Intervention (MITI) for medically underserved patients.
AB  - BACKGROUND: Insulin titration is typically done face-to-face with a clinician;
      however, this can be a burden for patients due to logistical issues associated
      with in-person clinical care. The Mobile Insulin Titration Intervention (MITI)
      used basic cell phone technology including text messages and phone calls to help
      patients with diabetes find their optimal basal insulin dose (OID). OBJECTIVE: To
      evaluate sociodemographic and clinical correlates of reaching OID, text message
      response rate, and days needed to reach OID. METHODS: Primary care providers
      referred patients to MITI and nurses delivered the program. Three multivariable
      regression models quantified relationships between various correlates and primary
      outcomes. RESULTS: The sample included 113 patients from 2 ambulatory clinics,
      with a mean age of 50 years (SD = 10), 45% female, 79% Hispanic, 43% unemployed,
      and 46% uninsured. In regression models, baseline fasting blood glucose (FBG) was
      negatively associated with odds of reaching OID and 100% text responses, and
      positively associated with days to reach OID, p < .05). CONCLUSIONS: Patients
      with higher baseline FBG levels were less successful across outcomes and may need
      additional supports in future mHealth diabetes programs. PRACTICAL IMPLICATIONS:
      Basic cell phone technology can be used to adjust patients' insulin remotely,
      thereby reducing logistical barriers to care.

PMID- 30293935
TI  - Preferences for surrogate designation and decision-making process in older versus
      younger adults with cancer: A comparative cross-sectional study.
AB  - OBJECTIVE: To compare the preferences of older (>=70 years old) versus younger
      (<70 years old) cancer patients regarding surrogate designation and decision
      making. METHODS: A cross-sectional survey. Patient characteristics and
      information about surrogacy and involvement in decision making were collected.
      Associations between patient characteristics and preferences were examined.
      RESULTS: The study included 130 patients aged >=70 years (mean age 80 years) and
      102 patients aged <70 years (mean age 55) and. Factors independently associated
      with surrogate knowledge (66%): younger age, more children living nearby, high
      income; factors associated with having already designated a surrogate (62%):
      younger age, decreased number of daily medications; factors associated with
      designating a surrogate after questionnaire administration (40%): low education,
      metastasis. Patients requiring an informed consent for any intervention was
      associated with older age (adjusted OR [aOR]per year = 1.04[95% confidence
      interval 1.00-1.08]), not living alone (aOR = 2.52[1.00-6.36]), and having
      children (aOR = 4.49[1.13-17.81]). CONCLUSION: All cancer patients, wanted to be
      fully informed and 72% wanted to be involved in medical decisions. Preferences
      for decision control vary between age groups, depending on family members'
      presence and living alone. PRACTICE IMPLICATIONS: Sharing complete and clear
      information should be an important key in the process of cancer patients' care,
      regardless of patient age.

PMID- 30293936
TI  - Autosomal dominant hypercholesterolemia in Catalonia: Correspondence between
      clinical-biochemical and genetic diagnostics in 967 patients studied in a
      multicenter clinical setting.
AB  - BACKGROUND: Autosomal dominant hypercholesterolemia (ADH) is associated with
      mutations in the low-density lipoprotein (LDL) receptor (LDLR), apolipoprotein B
      (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) genes, and it is
      estimated to be greatly underdiagnosed. The most cost-effective strategy for
      increasing ADH diagnosis is a cascade screening from mutation-positive probands.
      OBJECTIVE: The objective of this study was to evaluate the results from 2008 to
      2016 of ADH genetic analysis performed in our clinical laboratory, serving most
      lipid units of Catalonia, a Spanish region with approximately 7.5 million
      inhabitants. METHODS: After the application of the Dutch Lipid Clinic Network
      (DLCN) clinical diagnostic score for ADH, this information and blood or saliva
      from 23 different lipid clinic units were investigated in our laboratory. DNA was
      screened for mutations in LDLR, APOB, and PCSK9, using the DNA-array LIPOchip,
      the next-generation sequencing SEQPRO LIPO RS platform, and multiplex ligation
      dependent probe amplification (MLPA). The Simon Broome Register Group (SBRG)
      criteria was calculated and analyzed for comparative purposes. RESULTS: A total
      of 967 unrelated samples were analyzed. From this, 158 pathogenic variants were
      detected in 356 patients. The main components of the DLCN criteria associated
      with the presence of mutation were plasma LDL cholesterol (LDLc), age, and the
      presence of tendinous xanthomata. The contribution of family history to the
      diagnosis was lower than in other studies. DLCN and SBRG were similarly useful
      for predicting the presence of mutation. CONCLUSION: In a real clinical practice,
      multicenter setting in Catalonia, the percentage of positive genetic diagnosis in
      patients potentially affected by ADH was 38.6%. The DLCN showed a relatively low
      capacity to predict mutation detection but a higher one for ruling out mutation.

PMID- 30293937
TI  - Short- and long-term association of lipid-lowering drug treatment and
      cardiovascular disease by estimated absolute risk in the Second Australian
      National Blood Pressure study.
AB  - BACKGROUND: There is currently insufficient evidence to support the use of lipid
      lowering drug treatment (LLT) for primary prevention of cardiovascular disease
      (CVD) in the elderly. OBJECTIVES: We examined the relationship of early
      initiation of LLT with short- and long-term all-cause and CVD mortality in
      persons older than 65 years in this post hoc study from the Second Australian
      National Blood Pressure study (ANBP2). METHODS: This was an in- and post-trial
      observational study. About 4257 hypertensive participants aged 65 to 84 years
      within Australian family practices were randomized to an angiotensin-converting
      enzyme inhibitor or a diuretic treatment group. After excluding participants with
      a prior history of CVD, the cohort was stratified into "LLT" and "no LLT"
      subgroups based on LLT status at randomization. RESULTS: At randomization, the
      participants had a mean age of 72 years, average blood pressure of 168/91 mm Hg
      and estimated 5-year CVD risk of 18.7 +/- 8.3%. In the overall study population,
      the association of LLT with long-term (11-years) all-cause and non-CVD mortality
      was significant (hazard ratio [HR] 0.78 [95% confidence interval {CI} 0.66-0.92,
      P = .003] and HR 0.70 [95% CI 0.54-0.90, P = .006], respectively). Magnitudes of
      the association of LLT with long-term mortality and the association with short
      term mortality were similar; however, no statistically significant association
      with short-term mortality was observed. In the subgroup analysis by baseline 5
      year CVD risk, LLT participants in the highest risk tertile had a substantially
      lower relative risk for short-term all-cause mortality (HR 0.31, 95% CI 0.13
      0.71, P for interaction .02) compared to those with lower estimated CVD risk. All
      analyses were adjusted for baseline and in-trial characteristics. CONCLUSION: Our
      study showed a strong association between LLT and reduced long-term all-cause
      mortality. Thus, our findings support recommendations of the use of LLT in
      patients over 65 years, particularly those with high CVD risk who were more
      likely to obtain additional benefits in the short term. The findings also
      suggested that mortality benefits of LLT for the elderly may take longer to
      become evident.

PMID- 30293939
TI  - A Small Molecule Targeting the Transmembrane Domain of Death Receptor p75NTR
      Induces Melanoma Cell Death and Reduces Tumor Growth.
AB  - Small molecules offer powerful ways to alter protein function. However, most
      proteins in the human proteome lack small-molecule probes, including the large
      class of non-catalytic transmembrane receptors, such as death receptors. We
      hypothesized that small molecules targeting the interfaces between transmembrane
      domains (TMDs) in receptor complexes may induce conformational changes that alter
      receptor function. Applying this concept in a screening assay, we identified a
      compound targeting the TMD of death receptor p75NTR that induced profound
      conformational changes and receptor activity. The compound triggered apoptotic
      cell death dependent on p75NTR and JNK activity in neurons and melanoma cells,
      and inhibited tumor growth in a melanoma mouse model. Due to their small size and
      crucial role in receptor activation, TMDs represent attractive targets for small
      molecule manipulation of receptor function.

PMID- 30293938
TI  - ALDH1 Bio-activates Nifuroxazide to Eradicate ALDHHigh Melanoma-Initiating Cells.
AB  - 5-Nitrofurans are antibiotic pro-drugs that have potential as cancer
      therapeutics. Here, we show that 5-nitrofurans can be bio-activated by aldehyde
      dehydrogenase (ALDH) 1A1/1A3 enzymes that are highly expressed in a subpopulation
      of cancer-initiating (stem) cells. We discover that the 5-nitrofuran,
      nifuroxazide, is selective for bio-activation by ALDH1 isoforms over ALDH2,
      whereby it both oxidizes ALDH1 and is converted to cytotoxic metabolites in a two
      hit pro-drug mechanism. We show that ALDH1High melanoma cells are sensitive to
      nifuroxazide, while ALDH1A3 loss-of-function mutations confer drug resistance. In
      tumors, nifuroxazide targets ALDH1High melanoma subpopulations with the
      subsequent loss of melanoma-initiating cell potential. BRAF and MEK inhibitor
      therapy increases ALDH1 expression in patient melanomas, and effectively combines
      with nifuroxazide in melanoma cell models. The selective eradication of ALDH1High
      cells by nifuroxazide-ALDH1 activation goes beyond current strategies based on
      inhibiting ALDH1 and provides a rational basis for the nifuroxazide mechanism of
      action in cancer.

PMID- 30293940
TI  - Decoding Transcriptome Dynamics of Genome-Encoded Polyadenylation and
      Autoregulation with Small-Molecule Modulators of Alternative Polyadenylation.
AB  - Alternative polyadenylation (APA) plays a critical role in regulating gene
      expression. However, the balance between genome-encoded APA processing and
      autoregulation by APA modulating RNA binding protein (RBP) factors is not well
      understood. We discovered two potent small-molecule modulators of APA (T4 and T5)
      that promote distal-to-proximal (DtoP) APA usage in multiple transcripts.
      Monotonically responsive APA events, induced by short exposure to T4 or T5, were
      defined in the transcriptome, allowing clear isolation of the genomic sequence
      features and RBP motifs associated with DtoP regulation. We found that longer
      vulnerable introns, enriched with distinctive A-rich motifs, were preferentially
      affected by DtoP APA, thus defining a core set of genes with genomically encoded
      DtoP regulation. Through APA response pattern and compound-small interfering RNA
      epistasis analysis of APA-associated RBP factors, we further demonstrated that
      DtoP APA usage is partly modulated by altered autoregulation of polyadenylate
      binding nuclear protein-1 signaling.

PMID- 30293941
TI  - Antiarrhythmic Drugs Are not the Only Option in Electrical Storm: Extracorporeal
      Membrane Oxygenation as a Life-saving Alternative. Response.

PMID- 30293942
TI  - School Lunch Environmental Factors Impacting Fruit and Vegetable Consumption.
AB  - OBJECTIVE: Assess impact of school lunch environmental factors on fruit and
      vegetable (F&V) consumption in second and third grade students. DESIGN: Cross
      sectional observations in 1 school year. PARTICIPANTS: Students from 14
      elementary schools in 4 New York City boroughs (n = 877 student-tray
      observations). MAIN OUTCOME MEASURE(S): Dependent variables were F&V consumption
      collected by visual observation. Independent variables included school lunch
      environmental factors, and individual-level and school-level demographics.
      ANALYSIS: Hierarchical linear modeling was used with F&V consumption as the
      outcome variable, and relevant independent variables included in each model.
      RESULTS: Slicing or precutting of fruits and having lunch after recess were
      positively associated (P < .05) with .163- and .080-cup higher fruit consumption
      across all students, respectively. Preplating of vegetables on lunch trays,
      having 2 or more vegetable options, and having lunch after recess were positively
      associated (P < .05) with .024-, .009-, and .007-cup higher vegetable consumption
      across all students, respectively. CONCLUSIONS AND IMPLICATIONS: Although there
      was a small increase in intake, results of the study support that some school
      lunch environmental factors affect children's F&V consumption, with some factors
      leading to more impactful increases than others. Slicing of fruits seems most
      promising in leading to greater fruit consumption and should be further tested.

PMID- 30293943
TI  - Resistance to molecularly targeted therapy in non-small-cell lung cancer.
AB  - The discovery of oncogenic driver gene mutations, including epidermal growth
      factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion, ROS
      proto-oncogene 1 (ROS1) fusion, and ret proto-oncogene (RET) fusion, has led to
      the development of molecularly targeted therapy for non-small-cell lung cancer
      (NSCLC). This therapy has changed the standard of care for NSCLC. Despite the
      dramatic response to molecularly targeted therapy, almost all patients ultimately
      develop resistance to the drugs. To understand the mechanisms of resistance to
      molecularly targeted agents, it is essential to understand the molecular pathways
      of NSCLC. Here, we review the mechanisms of resistance to molecularly targeted
      therapy and discuss strategies to overcome drug resistance.

PMID- 30293944
TI  - Pemetrexed and carboplatin combination therapy followed by pemetrexed maintenance
      in Japanese patients with non-squamous non-small cell lung cancer: A subgroup
      analysis of elderly patients.
AB  - BACKGROUND: The combination of pemetrexed and carboplatin is commonly used for
      the treatment of advanced non-squamous non-small cell lung cancer (NSCLC), mainly
      because it is comparatively effective and less toxic than other platinum-doublet
      therapies. Using the JMII (JACAL) study, we report the efficacy and safety of
      this treatment followed by pemetrexed maintenance in the elderly population (>=70
      years of age). METHODS: The JMII study was a multicenter, post-marketing study
      that assessed the efficacy and safety of carboplatin (AUC6) and pemetrexed (500
      mg/m2, given on Day 1 of a 21-day cycle, 4 cycles) followed by pemetrexed (500
      mg/m2) maintenance in advanced non-squamous NSCLC patients (n = 109).
      Retrospective subgroup analyses were performed in elderly patients aged >=70.
      RESULTS: The study includes younger (<70 years, n = 84) and elderly (>=70 years,
      n = 25) patients who received induction therapy. Median progression-free survival
      and overall survival from the start of the induction phase were 5.2 (95% CI: 3.5,
      8.2) and 16.8 (95% CI: 10.3, NC) months for the elderly patients compared with
      5.8 (95% CI: 4.3, 7.4) and 20.5 (95% CI: 16.7, NC) months for the younger
      patients, respectively. Grade 3/4 hematologic toxicities were more frequent in
      the elderly patients. Non-hematologic toxicities in the elderly patients were
      comparable to those in younger patients. Dose reduction was more common in the
      elderly (44% vs 23%), due to hematologic toxicities. CONCLUSIONS: There was no
      difference in efficacy (evaluated by progression-free survival) between elderly
      and younger patients. Although grade 3/4 hematologic toxicities were frequently
      observed in the elderly patients, they were easily managed with dose adjustment.

PMID- 30293945
TI  - First-in-man Safety and Efficacy of the ClearRing Implant for the Treatment of
      Benign Prostatic Hyperplasia.
AB  - BACKGROUND: Although effective for benign prostatic hyperplasia (BPH),
      transurethral resection of the prostate (TURP) can be associated with side
      effects including prolonged recovery, storage and voiding symptoms, and a risk of
      acute urinary retention. OBJECTIVE: To test a new minimally invasive device for
      the treatment of lower urinary tract symptoms (LUTS) due to BPH, involving
      implantation of a C-shaped nitinol ring (ClearRing) in a circular incision in the
      prostatic tissue using an electrocuting blade over a dilatation balloon. DESIGN,
      SETTING, AND PARTICIPANTS: This was a multicenter single-arm clinical trial
      involving 29 men with severe symptomatic BPH. INTERVENTION: Implantation of a
      ClearRing device under regional anesthesia. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Effectiveness in alleviating LUTS was assessed in terms of
      International Prostate Symptom Score (IPSS) at baseline and 3, 6, and 12 mo after
      the procedure. To evaluate changes from baseline, a general estimating equation
      model was fitted to IPSS, the Quality of Life (QOL) scale, Benign Prostatic
      Hyperplasia Impact Index, maximum flow rate (Qmax), and postvoid residual volume.
      Statistical significance was defined as p<0.05. RESULTS AND LIMITATIONS: The
      average age was 71.4 yr, prostate size was 35-50cm3, and IPSS was 21.6. All
      procedures were successfully completed with one implant in 28 patients and two
      implants in one patient. No serious complications occurred. Patients experienced
      symptom relief by 3 mo that was sustained to 12 mo. Mean IPSS, QOL, and Qmax
      improved by 45%, 41%, and 40% by 3 mo, and 53%, 52%, and 49% by 12 mo,
      respectively (p<0.05). Adverse events were mild and transient. There were no
      reports of loss of antegrade ejaculation or any effects on erectile function.
      Implantation positioning failed in 11/29 patients, who then underwent uneventful
      TURP. After modification of the delivery device, the success rate for implant
      positioning improved from 5/13 patients to 13/16 patients. Study limitations
      include the single-arm nature and the low patient number. CONCLUSIONS: We
      demonstrated preliminary feasibility of the ClearRing device for minimally
      invasive treatment of BPH in men. Further studies are needed to confirm the
      safety and efficacy of this approach. PATIENT SUMMARY: In this study we tested
      outcomes after implantation of a ClearRing device in patients with benign
      prostatic hyperplasia. We found that the device was safe and effective. However,
      there was a high rate of implantation failure due to malpositioning, which was
      significantly improved following modification of the delivery device.

PMID- 30293946
TI  - Current Use of Three-dimensional Model Technology in Urology: A Road Map for
      Personalised Surgical Planning.
AB  - CONTEXT: Despite the current era of "precision surgery", an unmet need for an
      optimal surgical planning and navigation still remains for most genitourinary
      malignancies. In this setting, the 3D virtual reconstruction of 2D cross
      sectional imaging has been increasingly adopted to facilitate the surgeon in
      better understanding the surgical anatomy. OBJECTIVE: To provide a short overview
      of the most recent evidences on the current applications of 3D virtual and
      printed reconstructions in urologic surgery. EVIDENCE ACQUISITION: A non
      systematic review of the literature was performed. Medline, PubMed, the Cochrane
      Database and Embase were screened for studies regarding the use of 3D models in
      urology. EVIDENCE SYNTHESIS: 3D reconstruction technology has been primarily
      implemented with the purpose of surgical planning and navigation, especially in
      the management of prostate and kidney cancer. Augmented reality is still in a
      rudimental phase, especially in the field of prostate cancer. The (poor)
      Literature already published suggests that the 3D virtual and printed models
      could be helpful for the comprehension and learning of the surgical strategy by
      the young urologists and, at the meantime, could enhance the quality of the
      dialog with the patients, giving them a direct perception of the disease and its
      treatment. CONCLUSION: Notwithstanding the current limitations and the sporadic
      experiences available in the Literature, 3D models technology is perceived as a
      useful tool for the surgical planning, especially in the field of kidney and
      prostate cancer, physician education/training and patient counselling. PATIENT
      SUMMARY: In the field of prostate and kidney cancer, the optimal surgical
      planning and the patient counselling seems to be improved by the use of 3D
      reconstruction technology based on the preoperative imaging.

PMID- 30293947
TI  - [Obstetrical anal sphincter injuries and vacuum-assisted delivery at term in
      primiparas].
AB  - OBJECTIVES: Operative Vaginal Delivery (OVD) is subject to a risk of perineal
      tears especially of Obstetrical Anal Sphincter Injuries (OASIS) that are
      associated with more complications and impaired quality of life. The main
      objective of this study was to compare the rate of OASIS in primipara at term
      with fetus in cephalic presentation depending on the type of delivery: OVD using
      vacuum extractor and spontaneous delivery. METHODS: This is a single-center
      retrospective study between 01/01/2010 and 12/31/2014 including all primipara who
      delivered vaginally at term, a single and living fetus in cephalic presentation.
      Perineal lesions were classified according to the WHO classification. The primary
      endpoint was the proportion of OASIS. RESULTS: 3552 patients were included: 2496
      spontaneous deliveries (SD) and 1056 OVD (29.72 %). There were twenty sphincter
      tears (0.56 %): 7 in SD group (0.28 %) and 13 in OVD (1.23 %), P<0.0001, OR=5.10
      [2.00; 12.99]. Other risk factors associated with OASIS in univariable analysis
      were: maternal age (>=30 years), duration of expulsive efforts (>=20min) and a
      birth weight>=4000g. CONCLUSION: In these patients, the risk of OASIS in case of
      AI increases by a factor of 5;10. The high rate of AI in these patients exposes
      them to a real risk of OASIS. However, the proportion of OASIS in this group
      remains lower than those reported in the literature and is barely higher than the
      national overall rate, despite a very restrictive policy of the use of
      episiotomy.

PMID- 30293948
TI  - [Ulipristal acetate and SPRM: A new entity for the therapeutic strategy for
      symptomatic myomas].

PMID- 30293949
TI  - [Uterine rupture of the unscarred uterus: A report of 10 cases].
AB  - INTRODUCTION: Uterine rupture in the healthy uterus is a rare obstetrical
      complication, not much suspected and with badly identified risk factors. Thus,
      there exists frequent delay for treatment and therefore fetal-maternal important
      morbidity and mortality. This article describes clinical signs and symptoms,
      management, and maternal and neonatal prognosis of uterine rupture. METHODS:
      Descriptive retrospective study within 13 maternity hospitals, reporting 10
      series of cases of uterine rupture on gravid healthy uterus during the third
      trimester of pregnancy. RESULT: The incidence was 2.8/100,000 births. Surgical
      treatment was conservative in 9 out of 10 cases, the maternal prognosis was good
      with no maternal deaths and 6 out of 7 patients had at least one subsequent
      pregnancy. The fetal prognosis was more reserved, with 2 fetal or neonatal deaths
      and 1 with motor disability. 6/6 patients (100%) had at least one iterative
      Caesarean section during the following pregnancies with healthy fetuses.
      CONCLUSION: In this series of 10 cases over 25years, maternal-fetal morbidity and
      mortality were significant, in agreement with the literature. Maternal prognosis
      remained favorable. When surgical treatment is conservative a subsequent
      pregnancy is possible and an iterative cesarean section must be performed.

PMID- 30293950
TI  - The promising role of miR-296 in human cancer.
AB  - MicroRNAs (MiRNAs) are small non-protein-coding RNA molecules that silence mRNA
      translation; they have emerged as key players in nearly all biological processes
      in the past few decades. In particular, miRNAs are involved in carcinogenic
      processes, with either oncogenic or tumor suppressive roles in human cancers. The
      abnormal expression of miR-296 has important roles in various cellular processes
      inhuman malignancies, including cell proliferation, apoptosis, invasion, and
      epithelial-mesenchymal transition. Epigenetic mechanisms and upstream
      transcription factors are responsible for the regulation of miR-296 expression in
      cancer. In this review, we summarize and discuss the most recent findings
      regarding miR-296 in cancer, including its downstream targets, functional
      effects, underlying regulatory mechanisms, and therapeutic potentials.

PMID- 30293951
TI  - Strong androgen receptor expression is not useful in distinguishing GATA3 +
      metastases.
AB  - GATA binding protein 3 (GATA3) immunohistochemical expression is commonly
      considered to be a sensitive and specific diagnostic marker for breast and
      urothelial carcinomas in surgical pathology practice. However, since its
      expression has been also demonstrated in other tumors, GATA3 should be better
      used in conjunction with other immunohistochemical markers to establish tumor
      primitivity in metastatic setting. Interestingly, GATA3 expression seems to be
      significantly correlated with androgen receptor (AR) expression in breast
      carcinoma. In addition, strong AR expression -defined as immunohistochemical
      positivity in more than 60% of tumor cells- was suggested to be 100% specific for
      breast origin in GATA3+ metastases. The aim of this study was to verify whether
      strong AR expression may actually be useful to determine primivity in GATA3+
      metastatic setting. Thus, we investigated AR and GATA3 immuno-expression in a
      cohort of metastatic tumors derived from urothelial, breast, endometrial and
      salivary gland carcinomas. We did not find any GATA3 or AR expression in the
      metastases from endometrial or salivary gland carcinomas, while GATA3 expression
      was seen in the majority of metastases from urothelial or breast carcinomas. In
      addition, strong AR expression was seen in 73% and in 47% of metastatic breast
      and urothelial carcinomas, respectively. On the whole, our findings confirm that
      GATA3 is sensitive and specific for breast and urothelial origin in metastatic
      setting. According to our results, strong AR expression is not useful to
      distinguish breast from urothelial primitivity, as previously suggested.

PMID- 30293952
TI  - Clear cell dysplasia in a sessile serrated adenoma.

PMID- 30293953
TI  - FITC-labeled d-glucose analog is suitable as a probe for detecting insulin
      dependent glucose uptake.
AB  - The detection of the insulin-dependent glucose uptake is a vital part in the
      research of diabetes. To establish a sensitive assay for measuring glucose uptake
      in living cells, we synthesized a FITC linked d-glucosamine 2 as a probe. 2 was
      obtained by the reaction of commercially available d-glucosamine hydrochloride
      and FITC and was determined as a single anomeric form by 1H NMR and 13C NMR. 2
      exhibited good water solubility and stability. An uptake assay in HepG2 cells
      with or without insulin demonstrated that FITC showed strong cellular uptake,
      whereas uptake of 2 is much less but is insulin dependent. This suggests that 2
      is specifically transported into cells through a receptor that is regulated by
      insulin and has potential application in screening of compounds or genes that
      regulate the insulin-dependence in cell-based assays.

PMID- 30293955
TI  - Examination procedures and interventions for the hip in the management of low
      back pain: a survey of physical therapists.
AB  - OBJECTIVES: The main research aims were to investigate whether physical
      therapists are examining the hip(s) in individuals with a primary complaint of
      low back pain (LBP) and if so, the interventions being provided that target the
      hip(s). METHODS: An anonymous electronic survey was distributed to the membership
      of the American Physical Therapy Association Orthopaedic and Sports Sections, as
      well as that of the American Academy of Orthopaedic Manual Physical Therapists.
      Participant demographics and survey responses were analyzed using descriptive
      statistics. Associations between variables were examined using chi-square
      analysis. RESULTS: The estimated response rate was 18.4% (n=1163, mean age 40.5+/
      11.4 years). The majority of respondents (91%, n=1059) reported they always or
      most of the time examined the hip(s) in individuals with LBP. The most common
      examination items utilized were hip strength testing (94%, n=948), passive range
      of motion (91%, n=921) and muscle flexibility testing (90%, n=906). The most
      common interventions included hip strengthening (94%, n=866) and hip flexibility
      exercises (90%, n=814). Respondents enrolled in or having completed a post
      professional fellowship were more likely to utilize hip joint manual therapy
      techniques (x2=25.3, p=<0.001) and less likely to prescribe hip flexibility
      exercises (x2=7.9, p=0.005) or use electrophysical modalities (x2=4.3, p=0.039).
      CONCLUSIONS: Physical therapists commonly examine and provide interventions
      directed at the hip(s) for individuals with LBP. Post-professional fellowship
      training appears to influence the intervention selection of the physical
      therapist, with an increase in usage of hip joint manual therapy and a decrease
      in hip muscle flexibility and modality usage.

PMID- 30293954
TI  - Can high-intensity interval training change cardiac autonomic control? A
      systematic review.
AB  - BACKGROUND: High intensity interval training (HIIT) has been used as a
      cardiovascular exercise strategy to promote greater adherence in cardiovascular
      rehabilitation. However, little is known about the effect of this training
      modality on cardiac autonomic control. OBJECTIVE: To perform a systematic review
      to evaluate the effects of HIIT on cardiac autonomic responses in humans.
      METHODS: PEDro, SCOPUS and PubMed were searched from the inception to March 29th,
      2018. Moreover, the methodological quality and statistical reporting from all
      eligible clinical trials were assessed by the PEDro scale. The articles were
      eligible if: The primary objective was related to the effects of HIIT on the
      cardiac autonomic nervous system. Outcomes evaluated were indirect measures of
      cardiac autonomic control, represented by HRV indexes. RESULTS: The search
      strategies resulted in 339 citations and 2 additional citations were identified
      through other sources. After deleting the duplicate articles and revising the
      full text, 6 articles were included. Overall, the results showed an improvement
      in parasympathetic and/or sympathetic modulation after HIIT, when evaluated by
      linear and non-linear indexes of HRV. CONCLUSIONS: HIIT is a promising tool to
      improve the cardiac autonomic control, with more recommendation in healthy
      individuals and patients with metabolic syndrome.

PMID- 30293956
TI  - Associations between type and severity of hip pathology with pre-operative
      patient reported outcome measures.
AB  - BACKGROUND: The relationship between hip pathology and patient reported outcome
      responses following hip surgery has been previously investigated. No studies have
      investigated the relationship between pathology and patient reported outcome
      responses prior to surgery. OBJECTIVES: (1) Determine the prevalence of chondral
      and labral pathology identified during hip arthroscopy. (2) Determine the
      association between intra-articular findings and patient reported outcome scores
      in a pre-arthroscopy hip pain population. METHODS: Sixty-seven (22 female)
      participants scheduled for hip arthroscopy after clinical examination and
      radiographic assessment completed a series of patient reported outcomes (Hip
      Disability and Osteoarthritis Outcome Score; International Hip Outcome Tool; Pain
      on Activity; Visual Analogue Scale). Pathology discovered/addressed during
      arthroscopy was classified. Univariable and multivariable linear regression
      models were used to assess the relationship between demographics, pathology and
      patient reported outcome responses. RESULTS: Ninety-one percent of participants
      had labral pathology; 76% had acetabular chondropathy and 31% had femoral head
      chondropathy. Across the ten patient reported outcome subscales, severe femoral
      head chondropathy and large labral tears had the greatest number of significant
      associations with patient reported outcome scores. The strongest association was
      with 'Hip Disability and Osteoarthritis Outcome Score symptoms and stiffness'
      subscale, where severe femoral head chondropathy explained 22% of variability in
      symptoms and stiffness, when adjusted for Body Mass Index and presence of pincer
      morphology (p=0.002). CONCLUSION: Severe femoral head chondropathy and large
      labral tears along with a high prevalence of labral pathology and acetabular
      chondropathy were relatively common findings during hip arthroscopy. Severe
      femoral head chondropathy and large labral tears are most associated with patient
      reported outcome's, however, at best only explain 22% of the variability.

PMID- 30293957
TI  - Paediatric auditory brainstem implantation: The South Asian experience.
AB  - INTRODUCTION: Paediatric Auditory Brainstem Implantation (ABI) is indicated for
      children with congenital cochlear aplasia, absent/hypoplastic vestibulocochlear
      nerve, for whom cochlear implantation is not possible. Knowledge of the
      anatomical landmarks and variants in anatomy of the brainstem is vital for ABI
      surgery. METHOD: Study was done at Auditory implant centre in Madras ENT research
      foundation, which includes 24 children who had undergone ABI surgery and are
      being followed up for 1 year, post operatively. Aims were to study the anatomical
      variants and the outcomes of ABI implantation. To determine if different
      anatomical variants effect placement of ABI electrode. To assess the patient
      outcomes by Categories of auditory Performance (CAP) scores and Speech
      Intelligibility Ratings (SIR) scores. RESULTS: All the candidates showed gradual
      improvement in audiological and verbal outcomes after the ABI. The mean CAP and
      SIR scores after 6 months of AVHT were 2.07 and 1.37 respectively. After 1 year
      of auditory verbal rehabilitation therapy CAP was 3.42 and SIR was 2.33.
      Flocculus of the cerebellum can be of different grades. Though, there was
      difficulty in insertion of the electrode in subjects with anatomical variants,
      the outcomes were comparable with other subjects. CONCLUSION: ABI surgery
      involves frequent anatomical variations surrounding the lateral recess which
      makes the positioning of the auditory prosthesis difficult. Variants during the
      surgery can make the placement of ABI electrodes difficult, but promising results
      were seen all the implantees.

PMID- 30293958
TI  - Strategy for facial nerve management during surgical removal of benign jugular
      foramen tumors: Outcomes and indications.
AB  - OBJECTIVE: Classical surgical management of jugular foramen (JF) tumors usually
      requires facial nerve rerouting which results in permanent facial palsy in most
      patients. The purpose of the article is to study the outcomes of different
      rerouting techniques, and to discuss their indications. MATERIAL AND METHODS: We
      retrospectively reviewed 98 patients with JF tumors operated at our center
      between January 2008 and December 2016 using different surgical approaches with
      the following procedures for facial nerve management: total anterior rerouting
      (TR), partial anterior rerouting (PR), and fallopian bridge (FB) technique. The
      data for facial nerve management, surgical outcome and postoperative facial nerve
      function were collected from the medical records. RESULTS: In the study, there
      were 48 males and 50 females. Of them, 61 (62.2%) were jugular paragangliomas, 22
      (22.4%) schwannomas, and 15 (15.3%) meningiomas. Total tumor removal was achieved
      in 95 (96.9%) patients, while near-total removal was achieved in 3 (3.1%)
      paragangliomas. TR was applied in 31 (31.6%) patients with PR in 26 (26.5%)
      patients, and FB in 41 (41.8%) patients. The mean follow-up duration was 39.4+/
      22.6 months, and 2 recurrences of paragangliomas were observed. Seventy-five
      patients (76.5%) had good facial function (HB I-II) at 1 year after surgery, the
      patients who received a TR approach presented significantly less HB I-II FN
      function (48.4%) than those with PR (82.6%, P<0.05) or those with FB technique
      (95.1%, P<0.001). 21 patients (21.4%) presented new-onset lower cranial nerve
      dysfunction of which 13 recovered at 1 year after surgery. CONCLUSION: Facial
      nerve management in JF tumors should be tailored individually. No-rerouting
      methods, such as the fallopian bridge technique, bring significantly better
      results in terms of facial nerve function, which might be performed first during
      surgery; its indication is based mainly on the tumor type and extent.

PMID- 30293959
TI  - Resolvin E3 attenuates lipopolysaccharide-induced depression-like behavior in
      mice.
AB  - Eicosapentaenoic acid (EPA)-derived resolvin E1 (RvE1) and E2 (RvE2) have
      antidepressant effects. Here, we investigated the antidepressant effects of
      resolvin E3 (RvE3) in a mouse model of lipopolysaccharide (LPS)-induced
      depression. We observed that LPS (0.8 mg/kg, i.p.) significantly increased
      immobility time on the tail suspension test, and this depression-like behavior
      was dose-dependently attenuated by intracerebroventricular infusion of RvE3 (10
      or 100 ng). No effects of LPS or intracerebroventricular infusion of RvE3 on
      locomotor activity were observed. These results indicate that RvE3, as well as
      RvE1 and RvE2, have antidepressant effects.

PMID- 30293960
TI  - Anti-tumor activity of Escherichia coli Shiga toxin A subunit delivered by SF9
      insect cells.
AB  - Cancer remains a major health problem around the world. A Shiga toxin is a
      bacterial toxin often produced by Shigella dysenteriae and Escherichia coli. A
      subunit of the Shiga toxin (StxA) is a cytotoxic agent which could be used to
      induce death in cancer cells. StxA expressed from baculovirus was evaluated in a
      pTriExTM expression vector. The baculovirus vector was used for the A subunit
      delivery of StxA. StxA cell cytotoxicity was induced by the virus and assessed in
      the MCF7 and HeLa cell lines. In addition, the breast cancer cytotoxicity of the
      expressed StxA was also assessed in a cancer induced in mice. The cytotoxicity of
      the recombinant StxA baculovirus with different multiplicities of infection (MOI)
      was measured. The results showed that significant cytotoxicity can be induced on
      the mammalian epithelial breast cancer cell lines, MCF7 and HeLa cells with MOI
      >= 2. The results also showed that a malignant tumor induced by MCF7 could be
      inhibited in a mouse cancer model. Therefore, it can be concluded that StxA,
      expressed by baculovirus, could be used for in vitro and in vivo gene delivery.
      In this study StxA, delivered by the baculovirus inhibited cell proliferation,
      and eliminated HeLa and MCF7 cells, in vitro. In conclusion, this method can be
      used as a safe alternative for anticancer drug delivery inside cancer cells.

PMID- 30293961
TI  - Relationship between the fluorescence intensity of rhodamine-labeled orexin A and
      the calcium responses in cortical neurons: An in vivo two-photon calcium imaging
      study.
AB  - Neural responses to a ligand vary widely between neurons; however, the mechanisms
      underlying this variation remain unclear. One possible mechanism is a variation
      in the number of receptors expressed in each neural membrane. Here, we
      synthesized a rhodamine-labeled orexin A compound, enabling us to quantify the
      amount of orexin binding to its receptors, OX1 and OX2, which principally couple
      to the Gq/11 protein. The rhodamine intensity and calcium response were measured
      under tetrodotoxin application from insular cortical glutamatergic neurons in
      Thy1-GCaMP6s transgenic mice using an in vivo two-photon microscope. Applying
      rhodamine-labeled orexin A (10 MUM) to the cortical surface gradually and
      heterogeneously increased both the intensity of the rhodamine fluorescence and
      [Ca2+]i. Calcium responses started simultaneously with the increase in rhodamine
      labeled orexin fluorescence and reached a plateau within several minutes. We
      classified neurons as high- and low-responding neurons based on the peak
      amplitude of the [Ca2+]i increase. The rhodamine fluorescence intensity was
      larger in the high-responding neurons than the low-responding neurons.
      Preapplication of SB334867 and TCS-OX2-29, OX1 and OX2 antagonists, respectively,
      decreased the proportion of high-responding neurons. These results suggest that
      the diverse receptor expression level in neural membranes is involved in
      mechanisms underlying varied neural responses, including [Ca2+]i increases.

PMID- 30293962
TI  - Outcomes of shoulder abduction after nerve surgery in patients over 50 years
      following traumatic brachial plexus injury.
AB  - PURPOSE: There is controversy regarding the effectiveness of brachial plexus
      reconstruction in older patients, as outcomes are thought to be poor. The aim of
      this study is to determine the outcomes of shoulder abduction obtained after
      nerve reconstruction in patients over the age of 50 years and factors related to
      success. METHODS: Forty patients over the age of 50 years underwent nerve surgery
      to improve shoulder function after a traumatic brachial plexus injury. Patients
      were evaluated pre- and postoperatively for shoulder abduction strength and range
      of motion (ROM); Disability of the Arm, Shoulder and Hand (DASH) scores; pain;
      age bracket; gender; body mass index (BMI); delay from injury to operation;
      concomitant trauma; severity of trauma; and type of reconstruction. RESULTS: The
      average age was 58.2 years (range 50-77 years) with an average follow-up of 18.8
      months. The average modified British Medical Research Council (BMRC) shoulder
      abduction grade improved significantly from 0.23 to 2.03 (p < 0.005). Fourteen
      patients achieved functional shoulder abduction of >= M3 postoperatively. There
      was no correlation between age or age range stratification and BMRC grade or
      those obtaining useful shoulder abduction >= M3. Active shoulder abduction
      improved significantly from 18.25 degrees  to 40.64 degrees , with no difference
      on the basis of age or age stratification. There were improved modified BMRC
      grades with nerve transfers versus nerve grafts. Less patients achieved >= M3
      function if surgery was delayed > 6 months. The mean DASH score decreased from
      45.3 to 40.7 postoperatively, and the average pain score decreased from 3.7 to
      3.0. Patients with a higher postoperative BMRC grade for shoulder abduction had
      improved postoperative DASH scores and VAS for pain (p = 0.011 and 0.005,
      respectively). CONCLUSION: Brachial plexus nerve reconstruction for shoulder
      abduction in patients over the age of 50 years can yield useful BMRC scores and
      ROM, and age should not be used to exclude nerve reconstruction in these
      patients.

PMID- 30293963
TI  - Adipose-derived regenerative cells and fat grafting for treating breast cancer
      related lymphedema: Lymphoscintigraphic evaluation with 1 year of follow-up.
AB  - BACKGROUND: Breast cancer-related lymphedema (BCRL) is a feared late
      complication. Treatment options are lacking at present. Recent studies have
      suggested that mesenchymal stromal cells can alleviate lymphedema. Herein, we
      report the results from the first human pilot study with adipose-derived
      regenerative cells (ADRCs) for treating BCRL with 1 year of follow-up. MATERIAL
      AND METHODS: We included 10 patients with BCRL. ADRCs were injected directly into
      the axillary region together with a scar-releasing fat grafting procedure.
      Primary endpoint was change in arm volume. Secondary endpoints were change in
      patient-reported outcomes, changes in lymph flow, and safety. RESULTS: During
      follow-up, no significant change in volume was noted. Patient-reported outcomes
      improved significantly with time. Five patients reduced their use of conservative
      management. Quantitative lymphoscintigraphy did not improve on the lymphedema
      affected arms. ADRCs were well tolerated, and only minor transient adverse events
      related to liposuction were noted. CONCLUSIONS: In this pilot study, a single
      injection of ADRCs improved lymphedema based on patient-reported outcome
      measures, and there were no serious adverse events during the follow-up period.
      Lymphoscintigraphic evaluation showed no improvement after ADRC treatment. There
      was no change in excess arm volume. Results of this trial need to be confirmed in
      randomized clinical trials.

PMID- 30293964
TI  - Loss of cytosolic Mg2+ binding sites in the Thermotoga maritima CorA Mg2+ channel
      is not sufficient for channel opening.
AB  - The CorA Mg2+ channel is a homopentamer with five-fold symmetry. Each monomer
      consists of a large cytoplasmic domain and two transmembrane helices connected
      via a short periplasmic loop. In the Thermotoga maritima CorA crystal structure,
      a Mg2+ is bound between D89 of one monomer and D253 of the adjacent monomer (M1
      binding site). Release of Mg2+ from these sites has been hypothesized to cause
      opening of the channel. We generated mutants to disrupt Mg2+ interaction with the
      M1 site. Crystal structures of the D89K/D253K and D89R/D253R mutants, determined
      to 3.05 and 3.3 A, respectively, showed no significant structural differences
      with the wild type structure despite absence of Mg2+ at the M1 sites. Both
      mutants still appear to be in the closed state. All three mutant CorA proteins
      exhibited transport of 63Ni2+, indicating functionality. Thus, absence of Mg2+
      from the M1 sites neither causes channel opening nor prevents function. We also
      provide evidence that the T. maritima CorA is a Mg2+ channel and not a Co2+
      channel.

PMID- 30293966
TI  - The oligomeric plasticity of Hsp20 of Sulfolobus acidocaldarius protects
      environment-induced protein aggregation and membrane destabilization.
AB  - Small heat shock proteins (sHsps) are a ubiquitous family of molecular chaperones
      that rescue misfolded proteins from irreversible aggregation during cellular
      stress. Many such sHsps exist as large polydisperse species in solution, and a
      rapid dynamic subunit exchange between oligomeric and dissociated forms modulates
      their function under a variety of stress conditions. Here, we investigated the
      structural and functional properties of Hsp20 from thermoacidophilic crenarchaeon
      Sulfolobus acidocaldarius. To provide a framework for investigating the structure
      function relationship of Hsp20 and understanding its dynamic nature, we employed
      several biophysical and biochemical techniques. Our data suggested the existence
      of a ~24-mer of Hsp20 at room temperature (25  degrees C) and a higher oligomeric
      form at higher temperature (50  degrees C-70  degrees C) and lower pH (3.0-5.0).
      To our surprise, we identified a dimeric form of protein as the functional
      conformation in the presence of aggregating substrate proteins. The hydrophobic
      microenvironment mainly regulates the oligomeric plasticity of Hsp20, and it
      plays a key role in the protection of stress-induced protein aggregation. In
      Sulfolobus sp., Hsp20, despite being a non-secreted protein, has been reported to
      be present in secretory vesicles and it is still unclear whether it stabilizes
      substrate proteins or membrane lipids within the secreted vesicles. To address
      such an issue, we tested the ability of Hsp20 to interact with membrane lipids
      along with its ability to modulate membrane fluidity. Our data revealed that
      Hsp20 interacts with membrane lipids via a hydrophobic interaction and it lowers
      the propensity of in vitro phase transition of bacterial and archaeal lipids.

PMID- 30293965
TI  - The importance of the membrane interface as the reference state for membrane
      protein stability.
AB  - The insertion of nascent polypeptide chains into lipid bilayer membranes and the
      stability of membrane proteins crucially depend on the equilibrium partitioning
      of polypeptides. For this, the transfer of full sequences of amino-acid residues
      into the bilayer, rather than individual amino acids, must be understood. Earlier
      studies have revealed that the most likely reference state for partitioning very
      hydrophobic sequences is the membrane interface. We have used MUs-scale
      simulations to calculate the interface-to-transmembrane partitioning free
      energies DeltaGS->TM for two hydrophobic carrier sequences in order to estimate
      the insertion free energy for all 20 amino acid residues when bonded to the
      center of a partitioning hydrophobic peptide. Our results show that prior single
      residue scales likely overestimate the partitioning free energies of
      polypeptides. The correlation of DeltaGS->TM with experimental full-peptide
      translocon insertion data is high, suggesting an important role for the membrane
      interface in translocon-based insertion. The choice of carrier sequence greatly
      modulates the contribution of each single-residue mutation to the overall
      partitioning free energy. Our results demonstrate the importance of quantifying
      the observed full-peptide partitioning equilibrium, which is between membrane
      interface and transmembrane inserted, rather than combining individual water-to
      membrane amino acid transfer free energies.

PMID- 30293967
TI  - Pharmacological inhibition of autophagy by 3-MA attenuates hyperuricemic
      nephropathy.
AB  - Autophagy has been identified as a cellular process of bulk degradation of
      cytoplasmic components and its persistent activation is critically involved in
      the renal damage induced by ureteral obstruction. However, the role and
      underlying mechanisms of autophagy in hyperuricemic nephropathy (HN) remain
      unknown. In the present study, we observed that inhibition of autophagy by 3
      methyladenine (3-MA) abolished uric acid-induced differentiation of renal
      fibroblasts to myofibroblasts and activation of transforming growth factor-beta1
      (TGF-beta1), epidermal growth factor receptor (EGFR), and Wnt signaling pathways
      in cultured renal interstitial fibroblasts. Treatment with 3-MA also abrogated
      the development of HN in vivo as evidenced by improving renal function,
      preserving renal tissue architecture, reducing the number of autophagic vacuoles,
      and decreasing microalbuminuria. Moreover, 3-MA was effective in attenuating
      renal deposition of extracellular matrix (ECM) proteins and expression of alpha
      smooth muscle actin (alpha-SMA) and reducing renal epithelial cells arrested at
      the G2/M phase of cell cycle. Injury to the kidney resulted in increased
      expression of TGF-beta1 and TGFbeta receptor I, phosphorylation of Smad3 and TGF
      beta-activated kinase 1 (TAK1), and activation of multiple cell signaling
      pathways associated with renal fibrogenesis, including Wnt, Notch, EGFR, and
      nuclear factor-kappaB (NF-kappaB). 3-MA treatment remarkably inhibited all these
      responses. In addition, 3-MA effectively suppressed infiltration of macrophages
      and lymphocytes as well as release of multiple profibrogenic cytokines/chemokines
      in the injured kidney. Collectively, these findings indicate that hyperuricemia
      induced autophagy is critically involved in the activation of renal fibroblasts
      and development of renal fibrosis and suggest that inhibition of autophagy may
      represent a potential therapeutic strategy for HN.

PMID- 30293968
TI  - Spatial distribution of endogenous tissue protease activity in gastric carcinoma
      mapped by MALDI mass spectrometry imaging.
AB  - Aberrant protease activity has been implicated in the etiology of various
      prevalent diseases including neurodegeneration and cancer, in particular
      metastasis. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry
      imaging (MSI) has recently been established as a key technology for bioanalysis
      of multiple biomolecular classes such as proteins, lipids, and glycans. However,
      it has not yet been systematically explored for investigation of a tissue's
      endogenous protease activity. In this study, we demonstrate that different
      tissues, spray-coated with substance P as a tracer, digest this peptide with
      different time-course profiles. Furthermore, we reveal that distinct cleavage
      products originating from substance P are generated transiently and that
      proteolysis can be attenuated by protease inhibitors in a concentration-dependent
      manner. To show the translational potential of the method, we analyzed protease
      activity of gastric carcinoma in mice. Our MSI and quantitative proteomics
      results reveal differential distribution of protease activity - with strongest
      activity being observed in mouse tumor tissue, suggesting the general
      applicability of the workflow in animal pharmacology and clinical studies.

PMID- 30293971
TI  - Open-Label Placebo: Reflections on a Research Agenda.
AB  - Open-label placebos (OLP)-placebo pills honestly prescribed-have challenged the
      notion that placebos require either deception or concealment to evoke salubrious
      benefits. This essay describes how the author arrived at the counter-intuitive
      OLP hypothesis, discusses evidence for OLP effectiveness, and examines
      mechanistic explanations for OLP. Current dominant theories such as expectation
      and conditioning are found to be insufficient or inaccurate. The author proposes
      that emerging concepts of prediction and error processing (PEP), Bayesian brain,
      and embodied cognition are more appropriate models for understanding OLP. As a
      neural processing model, PEP argues that sensory predictions are embedded in and
      inseparable from perceptions; PEP circumvents mind-body dualism. The author
      discusses how OLP, mostly non-consciously, might perturb aberrant symptom
      amplifications and central sensitization resulting in perceptions of improvement
      in symptoms. Placebo effects are neurologically encoded predictions, less what
      patients think and more what they enact and perform.

PMID- 30293969
TI  - Effects of mipomersen, an apolipoprotein B100 antisense, on lipoprotein (a)
      metabolism in healthy subjects.
AB  - Elevated lipoprotein (a) [Lp(a)] levels increase the risk for CVD. Novel
      treatments that decrease LDL cholesterol (LDL-C) have also shown promise for
      reducing Lp(a) levels. Mipomersen, an antisense oligonucleotide that inhibits
      apoB synthesis, is approved for the treatment of homozygous familial
      hypercholesterolemia. It decreases plasma levels of LDL-C by 25% to 39% and
      lowers levels of Lp(a) by 21% to 39%. We examined the mechanisms for Lp(a)
      lowering during mipomersen treatment. We enrolled 14 healthy volunteers who
      received weekly placebo injections for 3 weeks followed by weekly injections of
      mipomersen for 7 weeks. Stable isotope kinetic studies were performed using
      deuterated leucine at the end of the placebo and mipomersen treatment periods.
      The fractional catabolic rate (FCR) of Lp(a) was determined from the enrichment
      of a leucine-containing peptide specific to apo(a) by LC/MS. The production rate
      (PR) of Lp(a) was calculated from the product of Lp(a) FCR and Lp(a)
      concentration (converted to pool size). In a diverse population, mipomersen
      reduced plasma Lp(a) levels by 21%. In the overall study group, mipomersen
      treatment resulted in a 27% increase in the FCR of Lp(a) with no significant
      change in PR. However, there was heterogeneity in the response to mipomersen
      therapy, and changes in both FCRs and PRs affected the degree of change in Lp(a)
      concentrations. Mipomersen treatment decreases Lp(a) plasma levels mainly by
      increasing the FCR of Lp(a), although changes in Lp(a) PR were significant
      predictors of reductions in Lp(a) levels in some subjects.

PMID- 30293970
TI  - Pharmacotherapy of pain in cancer patients - recommendations of the Polish
      Association for the Study of Pain, Polish Society of Palliative Medicine, Polish
      Society of Oncology, Polish Society of Family Medicine, Polish Society of
      Anaesthesiology and Intensive Therapy and Association of Polish Surgeons.
AB  - Guidelines for the pharmacotherapy of pain in cancer patients were developed by a
      group of 21 experts of the Polish Association for the Study of Pain, Polish
      Society of Palliative Medicine, Polish Society of Oncology, Polish Society of
      Family Medicine, Polish Society of Anaesthesiology and Intensive Therapy and
      Association of Polish Surgeons. During a series of meetings, the experts carried
      out an overview of the available literature on the treatment of pain in cancer
      patients, paying particular attention to systematic reviews and more recent
      randomized studies not included in the reviews. The search was performed in the
      EMBASE, MEDLINE, and Cochrane Central Register of Controlled Trials databases
      using such keywords as "pain", "cancer", "pharmacotherapy", "analgesics", and
      similar. The overviewed articles included studies of pathomechanisms of pain in
      cancer patients, methods for the assessment of pain in cancer patients, and drugs
      used in the pharmacotherapy of pain in cancer patients, including non-opioid
      analgesics (paracetamol, metamizole, non-steroidal anti-inflammatory drugs),
      opioids (strong and weak), coanalgesics (glucocorticosteroids, alpha2-adrenergic
      receptor agonists, NMDA receptor antagonists, antidepressants, anticonvulsants,
      topical medications) as well as drugs used to reduce the adverse effects of the
      analgesic treatment and symptoms other than pain in patients subjected to opioid
      treatment. The principles of opioid rotation and the management of patients with
      opioidophobia were discussed and recommendations for the management of opioid
      induced hyperalgesia were presented. Drugs used in different types of pain
      experienced by cancer patients, including neuropathic pain, visceral pain, bone
      pain, and breakthrough pain, were included in the overview. Most common
      interactions of drugs used in the pharmacotherapy of pain in cancer patients as
      well as the principles for the management of crisis situations. In the final part
      of the recommendations, the issues of pain and care in dying patients are
      discussed. Recommendations are addressed to physicians of different specialties
      involved in the diagnostics and treatment of cancer in their daily practice. It
      is the hope of the experts who took part in the development of these
      recommendations that the recommendations would become helpful in everyday medical
      practice and thus contribute to the improvement in the quality of care and the
      efficacy of pain treatment in this group of patients.

PMID- 30293972
TI  - Reining in the Placebo Effect.
AB  - What is known as the "placebo effect" has received increasing attention in recent
      years in scientific investigation and the news media. The concept of the placebo
      effect, however, is subject to confusion and misleading implications, especially
      when applied broadly. This essay argues that it is desirable to confine the
      concept, as applied to biomedicine, to the therapeutic effects of deliberate
      placebo interventions. The author examines in detail the conceptual problems in
      characterizing the therapeutic benefits that flow from communication in the
      clinician-patient relationship as placebo effects.

PMID- 30293973
TI  - Editors' Introduction to Special Section on Meaning Response and the Placebo
      Effect.

PMID- 30293974
TI  - Meaning and an Overview of the Placebo Effect.
AB  - The placebo effect can be defined as a bodily change due to the symbolic effects
      of a treatment or treatment situation. It is further explained by the meaning
      model: a positive placebo response is most likely to occur when the meaning of
      the illness is altered for the patient in a positive direction. Moerman's
      suggestion that "placebo effect" be replaced by "meaning response" is based in
      part on dissatisfaction with the characterization of placebo, which is avoided
      when one focuses instead more comprehensively on placebo effect. The placebo
      effect can then be explained by the mental processes of expectancy or
      conditioning and their effect on specific neuro-chemical processes that bring
      about end-organ changes.

PMID- 30293975
TI  - The Meaning Response, "Placebo," and Methods.
AB  - In 2002, Dan Moerman outlined three candidate explanations for the "placebo
      response": the "conditioned stimulus-response," Irving Kirsch's "response
      expectancy" explanation, and the "meaning response." The meaning response,
      Moerman argued, was the only one of the three candidate explanations that could
      cover all the data, gained from decades of RCTs and centuries of historical
      record. Moerman went so far as to propose replacing the term "placebo
      effect/response" with the term "meaning response," because people are not
      responding to placebos, since there is nothing to respond to; people are
      responding to meanings. There is evidence of medically significant meaning
      responses where there is no evidence for conditioning. Similarly, there is
      evidence for such responses where those subject to them lack the knowledge
      epistemic capital-required to form the beliefs which might constitute an
      expectation. Something else, neither conditioning nor propositional attitudes,
      explained placebo responses, and Moerman proposed the meaning response. While the
      authors consider the meaning response to avoid the pitfalls of conditioning and
      response-expectancy, it has been subject to criticism. The criticisms have
      focused on what is seen as the explanation falling foul of the naturalistic
      demand and not fitting with prevalent predilections in the philosophy of mind and
      cognitive science. This article seeks to allay these worries and proposes the
      inclusion of ethnomethodological fieldwork in future research.

PMID- 30293976
TI  - A Critical (and Cautiously Optimistic) Appraisal of Moerman's "Meaning Response".
AB  - In this article we propose a critical reassessment of Daniel Moerman's "meaning
      response." First, we reconstruct and criticize Moerman's original proposal of
      introducing the "meaning response" as a way of clarifying some terminological and
      conceptual issues in the placebo debate. Next we evaluate the criticisms that
      Moerman's proposal is epistemically moot since other existing and more
      empirically grounded models already account for all the phenomena that fall under
      the concept of the "meaning response." We conclude that Moerman's original
      proposal is inherently problematic and that, in order to be instrumentally useful
      in the future, the meaning response must be reconceived so that it may finally
      support, rather than oppose, other theoretical and empirical lines of research
      currently ongoing in the field of placebo studies.

PMID- 30293978
TI  - What Are the Benefits of a New Placebo Language?
AB  - This article examines three common strategies for dealing with the problems
      generated by the terms placebo and "placebo effect." These strategies are to
      redefine, to reconceptualize, and to eliminate our placebo language. The promise
      of these strategies is that a new language for talking about placebo phenomena
      may deliver clinical, ethical, and methodological advances. However, the nature
      and impact of these advances is rarely explored in detail. This article surveys
      some of the promised benefits of new terms such as "meaning response" and
      "contextual healing." The benefits are broadly similar across these strategies,
      but while they allow for clearer descriptions of phenomena and wider appreciation
      of the contextual aspects of medical practice, the open challenge for these
      strategies is not just to promise, but to show, the practical significance of
      their approaches to understanding placebo phenomena.

PMID- 30293979
TI  - Consensus in Placebo Studies: Lessons from The Philosophy of Science.
AB  - In the relatively nascent field of placebo studies, empirical studies have
      burgeoned. Yet debate about how to define the terms placebo and "placebo effect"
      has not abated. A number of prominent scholars (drawn from medical practice, as
      well as philosophy, psychology, and anthropology) continue to propose and defend
      different conceptual models for these terms, and the perception that conceptual
      debate persists is often given as one justification for new definitions.
      Paradoxically-in spite of this lively debate-this article finds considerable
      underlying agreement about definitional matters within placebo studies. Drawing
      on key insights from philosophy of science, and by exploring the nature of
      scientific consensus and normal scientific research, this paper argues that well
      developed placebo concepts form the basis for a placebo paradigm and that
      conceptual disagreement is overstated.

PMID- 30293977
TI  - The Placebo Phenomenon: A Narrow Focus on Psychological Models.
AB  - The placebo effect is a complex phenomenon that can be described from
      neurobiological, psychosocial, and epistemological perspectives. Different
      leaders in the field have proposed multiple theories and models that attempt to
      describe both the nature and the mechanisms of action underlying placebo effects.
      This article focuses on the most relevant psychological models that have been
      suggested for characterizing the different mechanisms underlying the placebo
      effect. We outline how the dynamic psychoneurobiological aspects of the placebo
      phenomenon can be a potential reliable and useful tool in daily clinical practice
      for illness and symptom management within a wide variety of specialties and
      health-care practices.

PMID- 30293980
TI  - 200 Years After Frankenstein.
AB  - Mary Shelley's Frankenstein is 200 years old and remains relevant to 21st-century
      scientific experimentation. Molecular biologists today have become especially
      bold in their attempts to cure diseases while remaining mindful of the real
      dangers of their research. Scientists presumably share an abiding concern about
      producing uncontrollable mutations in people, animals, and the wider environment,
      yet a sense of urgency appears to inform the current scientific willingness to
      take risks, especially in the realm of embryology and germ-line modification.
      This willingness to go more boldly than before could be influenced by the
      unprecedented ability of such gene-cutting technologies as CRISPR to make
      immediate and lasting improvements to persons suffering from certain diseases and
      other physical malignancies, but also by an acculturated sense that such persons
      deserve to participate more fully in broader society.

PMID- 30293981
TI  - Who's Winning the IRB Wars? The Struggle for the Soul of Human Research.
AB  - The origins and aspirations of institutional review boards (IRBs), the American
      oversight system for research with human subjects, are well known, and their
      failures have been documented and disputed for decades. Contention about IRBs is
      often ideological and unsatisfying, but their shortcomings are real. A new wave
      of attention to the promise and problems of this oversight system has coincided
      with the years-long effort to update the federal "Common Rule." Three very
      different recent books-Rebecca Dresser's Silent Partners, Robert Klitzman's
      Ethics Police, and Carl Schneider's The Censor's Hand-draw from a wealth of
      experiential, empirical, and rhetorical resources to triangulate this long
      standing set of concerns and tensions at individual, institutional, and system
      levels. Schneider's volume exemplifies anti-government critiques of the
      regulation of science; Klitzman's catalogues IRB members' reflections on the
      ambiguities inherent in their regulatory role; and, by far the most
      interestingly, Dresser examines the potential contributions of experienced
      research subjects to the oversight process. Taken together, these books can help
      refocus the IRB wars on the ever-challenging relationships among goals,
      uncertainties, and practicalities, and move us toward understanding and
      addressing those relationships in their current (and rapidly changing) scientific
      and societal context. Some real progress might even result.

PMID- 30293982
TI  - Job Satisfaction Among Doctors from Jiangsu Province in China.
AB  - BACKGROUND Doctors' job satisfaction has an important effect on medical and
      health services. This study assessed the level of job satisfaction in Chinese
      doctors and explored how influencing factors differ between general practitioners
      and specialists. MATERIAL AND METHODS The Minnesota Satisfaction Questionnaire
      (MSQ) on job satisfaction was distributed to 1883 doctors in Jiangsu province,
      including 850 general practitioners and 1033 specialists. Data analysis was
      performed with SPSS 20.0. A one-way ANOVA was used to analyze doctors' job
      satisfaction and logistic regression analysis was used for multivariate analysis.
      Correlation analysis was done on the 5 dimensions of satisfaction. RESULTS The
      average MSQ score of all surveyed doctors was 3.11+/-0.87, with general
      practitioners (GPs) and specialists scores of 2.81+/-0.84 and 3.35+/-0.82,
      respectively. Analysis of doctor satisfaction indicated that gender, age, marital
      status, educational attainment, professional title, and seniority were
      statistically significant (P<0.05). Overall satisfaction was most closely related
      to the job itself (r=0.96); work, work environment, and interpersonal
      relationship were closely related with lead management. CONCLUSIONS The level of
      job satisfaction of Chinese doctors, especially general practitioners, needs to
      be improved. Measures such as improving education levels, work environment, and
      relationships should to be taken soon to improve doctors' job satisfaction in
      China.

PMID- 30293983
TI  - Eosinophilic Granulomatosis with Polyangiitis (EGPA) with an Unusual
      Manifestation of Mid-Ventricular Obstruction Caused by Endocardial Thrombus.
AB  - BACKGROUND Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare
      systemic vasculitis of unknown cause accompanied by prominent eosinophilia.
      Intracardiac thrombosis is one of the major cardiac complications in EGPA that
      may cause thromboembolism. CASE REPORT A 46-year-old male presenting with
      intermittent chest pain and numbness of the lower extremities was admitted to our
      center. His case was complicated by multiple brain infarcts and endocardial
      thrombosis in the left ventricle. A condition of restrictive cardiomyopathy was
      also found. After a thorough workup, he was diagnosed with antineutrophil
      cytoplasmic antibody (ANCA) positive EGPA. Interestingly, the thrombus was
      accompanied by a pressure gradient producing mid-ventricular obstruction. The
      patient improved reasonably with immunosuppression and anticoagulation treatment,
      in addition to heart failure treatment, and had a concomitant regression of the
      thrombus and reduction of the pressure gradient. CONCLUSIONS For an EGPA patient
      complicated by intraventricular obstruction caused by endocardial thrombosis,
      which could accelerate the release of the thrombus into the systemic circulation
      resulting in a life-threating condition, timely and aggressive measures against
      cardioembolic complications should be considered.

PMID- 30293984
TI  - Long-range PCR libraries and next-generation sequencing for pharmacogenetic
      studies of patients treated with anti-TNF drugs.
AB  - Biological therapy with anti-tumor necrosis factor-alpha (anti-TNF-alpha)
      monoclonal antibodies significantly increased the effectiveness of autoimmune
      disease treatment compared with conventional medicines. However, anti-TNF-alpha
      drugs are relatively expensive and a response to the therapy is reported in only
      60-70% of patients. Moreover, in up to 5% of patients adverse drug reactions
      occur. The various effects of biological treatment may be a potential consequence
      of interindividual genetic variability. Only a few studies have been conducted in
      this field and which refer to single gene loci. Our aim was to design and
      optimize a methodology for a broader application of pharmacogenetic studies in
      patients undergoing anti-TNF-alpha treatment. Based on the current knowledge, we
      selected 16 candidate genes: TNFRSF1A, TNFRSF1B, ADAM17, CASP9, FCGR3A, LTA, TNF,
      FAS, IL1B, IL17A, IL6, MMP1, MMP3, S100A8, S100A9, and S100A12, which are
      potentially involved in the response to anti-TNF-alpha therapy. As a research
      model, three DNA samples from Crohn's disease (CD) patients were used. Targeted
      genomic regions were amplified in 23 long-range (LR) PCR reactions and after
      enzymatic fragmentation amplicon libraries were prepared and analyzed by next
      generation sequencing (NGS). Our results indicated 592 sequence variations
      located in all fragments with coverage range of 5-1089. We demonstrate a highly
      sensitive, flexible, rapid, and economical approach to the pharmacogenetic
      investigation of anti-TNF-alpha therapy using amplicon libraries and NGS
      technology.

PMID- 30293985
TI  - The IICR and the non-stationary structured coalescent: towards demographic
      inference with arbitrary changes in population structure.
AB  - In the last years, a wide range of methods allowing to reconstruct past
      population size changes from genome-wide data have been developed. At the same
      time, there has been an increasing recognition that population structure can
      generate genetic data similar to those produced under models of population size
      change. Recently, Mazet et al. (Heredity 116:362-371, 2016) showed that, for any
      model of population structure, it is always possible to find a panmictic model
      with a particular function of population size changes, having exactly the same
      distribution of T2 (the coalescence time for a sample of size two) as that of the
      structured model. They called this function IICR (Inverse Instantaneous
      Coalescence Rate) and showed that it does not necessarily correspond to
      population size changes under non-panmictic models. Besides, most of the methods
      used to analyse data under models of population structure tend to arbitrarily fix
      that structure and to minimise or neglect population size changes. Here, we
      extend the seminal work of Herbots (PhD thesis, University of London, 1994) on
      the structured coalescent and propose a new framework, the Non-Stationary
      Structured Coalescent (NSSC) that incorporates demographic events (changes in
      gene flow and/or deme sizes) to models of nearly any complexity. We show how to
      compute the IICR under a wide family of stationary and non-stationary models. As
      an example we address the question of human and Neanderthal evolution and discuss
      how the NSSC framework allows to interpret genomic data under this new
      perspective.

PMID- 30293986
TI  - Copy-number variants in clinical genome sequencing: deployment and interpretation
      for rare and undiagnosed disease.
AB  - PURPOSE: Current diagnostic testing for genetic disorders involves serial use of
      specialized assays spanning multiple technologies. In principle, genome
      sequencing (GS) can detect all genomic pathogenic variant types on a single
      platform. Here we evaluate copy-number variant (CNV) calling as part of a
      clinically accredited GS test. METHODS: We performed analytical validation of CNV
      calling on 17 reference samples, compared the sensitivity of GS-based variants
      with those from a clinical microarray, and set a bound on precision using
      orthogonal technologies. We developed a protocol for family-based analysis of GS
      based CNV calls, and deployed this across a clinical cohort of 79 rare and
      undiagnosed cases. RESULTS: We found that CNV calls from GS are at least as
      sensitive as those from microarrays, while only creating a modest increase in the
      number of variants interpreted (~10 CNVs per case). We identified clinically
      significant CNVs in 15% of the first 79 cases analyzed, all of which were
      confirmed by an orthogonal approach. The pipeline also enabled discovery of a
      uniparental disomy (UPD) and a 50% mosaic trisomy 14. Directed analysis of select
      CNVs enabled breakpoint level resolution of genomic rearrangements and phasing of
      de novo CNVs. CONCLUSION: Robust identification of CNVs by GS is possible within
      a clinical testing environment.

PMID- 30293987
TI  - Identification of clinically actionable variants from genome sequencing of
      families with congenital heart disease.
AB  - PURPOSE: Congenital heart disease (CHD) affects up to 1% of live births. However,
      a genetic diagnosis is not made in most cases. The purpose of this study was to
      assess the outcomes of genome sequencing (GS) of a heterogeneous cohort of CHD
      patients. METHODS: Ninety-seven families with probands born with CHD requiring
      surgical correction were recruited for genome sequencing. At minimum, a proband
      parents trio was sequenced per family. GS data were analyzed via a two-tiered
      method: application of a high-confidence gene screen (hcCHD), and comprehensive
      analysis. Identified variants were assessed for pathogenicity using the American
      College of Medical Genetics and Genomics-Association for Molecular Pathology
      (ACMG-AMP) guidelines. RESULTS: Clinically relevant genetic variants in known and
      emerging CHD genes were identified. The hcCHD screen identified a clinically
      actionable variant in 22% of families. Subsequent comprehensive analysis
      identified a clinically actionable variant in an additional 9% of families in
      genes with recent disease associations. Overall, this two-tiered approach
      provided a clinically relevant variant for 31% of families. CONCLUSIONS:
      Interrogating GS data using our two-tiered method allowed identification of
      variants with high clinical utility in a third of our heterogeneous cohort.
      However, association of emerging genes with CHD etiology, and development of
      novel technologies for variant assessment and interpretation, will increase
      diagnostic yield during future reassessment of our GS data.

PMID- 30293989
TI  - Long-term follow-up in PMM2-CDG: are we ready to start treatment trials?
AB  - PURPOSE: PMM2-CDG is the most common congenital disorder of glycosylation (CDG),
      which presents with either a neurologic or multisystem phenotype. Little is known
      about the longitudinal evolution. METHODS: We performed data analysis on PMM2-CDG
      patients' clinical features according to the Nijmegen CDG severity score and
      laboratory data. Seventy-five patients (28 males) were followed up from 11.0 +/-
      6.91 years for an average of 7.4 +/- 4.5 years. RESULTS: On a group level, there
      was no significant evolution in overall clinical severity. There was some
      improvement in mobility and communication, liver and endocrine function, and
      strabismus and eye movements. Educational achievement and thyroid function
      worsened in some patients. Overall, the current clinical function, the system
      specific involvement, and the current clinical assessment remained unchanged. On
      follow-up there was improvement of biochemical variables with (near)
      normalization of activated partial thromboplastin time (aPTT), factor XI, protein
      C, antithrombin, thyroid stimulating hormone, and liver transaminases.
      CONCLUSION: PMM2-CDG patients show a spontaneous biochemical improvement and
      stable clinical course based on the Nijmegen CDG severity score. This information
      is crucial for the definition of endpoints in clinical trials.

PMID- 30293988
TI  - De novo missense variants in RAC3 cause a novel neurodevelopmental syndrome.
AB  - PURPOSE: RAC3 is an underexamined member of the Rho GTPase gene family that is
      expressed in the developing brain and linked to key cellular functions. De novo
      missense variants in the homolog RAC1 were recently associated with developmental
      disorders. In the RAC subfamily, transforming missense changes at certain shared
      residues have been observed in human cancers and previously characterized in
      experimental studies. The purpose of this study was to determine whether
      constitutional dysregulation of RAC3 is associated with human disease. METHODS:
      We discovered a RAC3 variant in the index case using genome sequencing, and
      searched for additional variants using international data-sharing initiatives.
      Functional effects of the variants were assessed using a multifaceted approach
      generalizable to most clinical laboratory settings. RESULTS: We rapidly
      identified five individuals with de novo monoallelic missense variants in RAC3,
      including one recurrent change. Every participant had severe intellectual
      disability and brain malformations. In silico protein modeling, and prior in vivo
      and in situ experiments, supported a transforming effect for each of the three
      different RAC3 variants. All variants were observed in databases of somatic
      variation in cancer. CONCLUSIONS: Missense variants in RAC3 cause a novel brain
      disorder, likely through a mechanism of constitutive protein activation.

PMID- 30293990
TI  - Molecular autopsy by trio exome sequencing (ES) and postmortem examination in
      fetuses and neonates with prenatally identified structural anomalies.
AB  - PURPOSE: To determine the diagnostic yield of combined exome sequencing (ES) and
      autopsy in fetuses/neonates with prenatally identified structural anomalies
      resulting in termination of pregnancy, intrauterine, neonatal, or early infant
      death. METHODS: ES was undertaken in 27 proband/parent trios following full
      autopsy. Candidate pathogenic variants were classified by a multidisciplinary
      clinical review panel using American College of Medical Genetics and Genomics
      (ACMG) guidelines. RESULTS: A genetic diagnosis was established in ten cases
      (37%). Pathogenic/likely pathogenic variants were identified in nine different
      genes including four de novo autosomal dominant, three homozygous autosomal
      recessive, two compound heterozygous autosomal recessive, and one X-linked. KMT2D
      variants (associated with Kabuki syndrome postnatally) occurred in two cases.
      Pathogenic variants were identified in 5/13 (38%) cases with multisystem
      anomalies, in 2/4 (50%) cases with fetal akinesia deformation sequence, and in
      1/4 (25%) cases each with cardiac and brain anomalies and hydrops fetalis. No
      pathogenic variants were detected in fetuses with genitourinary (1), skeletal
      (1), or abdominal (1) abnormalities. CONCLUSION: This cohort demonstrates the
      clinical utility of molecular autopsy with ES to identify an underlying genetic
      cause in structurally abnormal fetuses/neonates. These molecular findings
      provided parents with an explanation of the developmental abnormality, delineated
      the recurrence risks, and assisted the management of subsequent pregnancies.

PMID- 30293991
TI  - Pitfalls of clinical exome and gene panel testing: alternative transcripts.
AB  - PURPOSE: Clinical exome and gene panel testing can provide molecular diagnoses
      for patients with rare Mendelian disorders, but for many patients these tests are
      nonexplanatory. We investigated whether interrogation of alternative transcripts
      in known disease genes could provide answers for additional patients. METHODS: We
      integrated alternative transcripts for known neonatal epilepsy genes with RNA-Seq
      data to identify brain-expressed coding regions that are not evaluated by popular
      neonatal epilepsy clinical gene panel and exome tests. RESULTS: We found brain
      expressed alternative coding regions in 89 (30%) of 292 neonatal epilepsy genes.
      The 147 regions encompass 15,713 bases that are noncoding in the primary
      transcripts analyzed by the clinical tests. Alternative coding regions from at
      least 5 genes carry reported pathogenic variants. Three candidate variants in
      these regions were identified in public exome data from 337 epilepsy patients.
      Incorporating alternative transcripts into the analysis of neonatal epilepsy
      genes in 44 patient genomes identified the pathogenic variant for the epilepsy
      case and 2 variants of uncertain significance (VUS) among the 43 control cases.
      CONCLUSION: Assessment of alternative transcripts in exon-based clinical genetic
      tests, including gene panel, exome, and genome sequencing, may provide diagnoses
      for patients for whom standard testing is unrevealing, without introducing many
      VUS.

PMID- 30293992
TI  - Variant data sharing by clinical laboratories through public databases: consent,
      privacy and further contact for research policies.
AB  - Access to detailed variant data is key to inform and verify the interpretation of
      genomic data. Clinical laboratories can play a significant role in sharing
      patients' data through public variant databases. To facilitate data sharing,
      various public databases, such as ClinVar and DECIPHER have been established,
      which accept data submission from laboratories, clinicians, researchers, and
      patients. Despite clear benefits to sharing, questions may arise about the
      adequate form of consent to be obtained from patients when sharing data from
      their clinical tests through public databases. In this paper, we provide an
      overview and critical analysis of the relevant consent policies of the major
      public databases, and of the consent forms of clinical laboratories that share
      variant data via ClinVar.

PMID- 30293993
TI  - First Degree Relatives of Patients with Celiac Disease Harbour an Intestinal
      Transcriptomic Signature that Might Protect them from Enterocyte Damage.
AB  - INTRODUCTION: Celiac disease (CeD) is an autoimmune enteropathy which affects
      approximately 0.7% of the global population. While first-degree relatives (FDR)
      of patients with CeD have a 7.5% risk of developing enteropathy, many remain
      protected. Therefore, intestinal mucosa of FDR might have protective compensatory
      mechanisms against immunological injury. We have explored the protective
      mechanisms that may be active in intestinal mucosa of FDR. METHODS: Intestinal
      mucosal biopsies (4-5 pieces) from treatment naive patients with CeD (n = 12),
      FDR (n = 12) (anti-tTG negative) and controls (n = 12) (anti-tTG negative) were
      obtained from each individual and subjected to microarray analysis using HT-12-v4
      Human Expression BeadChips (Illumina). Differential gene expression analysis was
      carried out among CeD, FDR and controls; and resulting gene lists were analyzed
      using gene ontology and pathway enrichment tools. RESULTS: Patients with CeD, FDR
      and control groups displayed significant differential gene expression. Thirty
      seven genes were upregulated and 372 were downregulated in the intestinal mucosa
      of FDR in comparison to CeD and controls. Pseudogenes constituted about 18%
      (315/1751) of FDR differentially expressed genes, and formed "clusters" that
      associated uniquely with individual study groups. The three study groups
      segregated into distinct clusters in unsupervised (PCA) and supervised (random
      forests) modelling approaches. Pathways analysis revealed an emphasis on crypt
      villous maintenance and immune regulation in the intestinal mucosa of FDR.
      CONCLUSIONS: Our analysis suggests that the intestinal mucosa of celiac FDR
      consist of a unique molecular phenotype that is distinct from CeD and controls.
      The transcriptomic landscape of FDR promotes maintenance of crypt-villous axis
      and modulation of immune mechanisms. These differences clearly demonstrate the
      existence of compensatory protective mechanisms in the FDR intestinal mucosa.

PMID- 30293995
TI  - Phase II trial of palbociclib in patients with metastatic urothelial cancer after
      failure of first-line chemotherapy.
AB  - BACKGROUND: The majority of urothelial cancers (UC) harbor alterations in
      retinoblastoma (Rb) pathway genes that can lead to loss of Rb tumour suppressor
      function. Palbociclib is an oral, selective inhibitor of CDK 4/6 that restores Rb
      function and promotes cell cycle arrest. METHODS: In this phase II trial,
      patients with metastatic platinum-refractory UC molecularly selected for p16 loss
      and intact Rb by tumour immunohistochemistry received palbociclib 125 mg p.o.
      daily for 21 days of a 28-day cycle. Primary endpoint was progression-free
      survival at 4 months (PFS4) using a Simon's two-stage design. Next-generation
      sequencing including Rb pathway alterations was conducted. RESULTS: Twelve
      patients were enrolled and two patients (17%) achieved PFS4 with insufficient
      activity to advance to stage 2. No responses were seen. Median PFS was 1.9 months
      (95% CI 1.8-3.7 months) and median overall survival was 6.3 months (95% CI 2.2
      12.6 months). Fifty-eight percent of patients had grade >=3 hematologic toxicity.
      There were no CDKN2A alterations found and no correlation of Rb pathway
      alterations with clinical outcome. CONCLUSIONS: Palbociclib did not demonstrate
      meaningful activity in selected patients with platinum-refractory metastatic UC.
      Further development of palbociclib should only be considered with improved
      integral biomarker selection or in rational combination with other therapies.

PMID- 30293994
TI  - MicroRNA-transcription factor network analysis reveals miRNAs cooperatively
      suppress RORA in oral squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) represents over 90% of oral cancer incidence,
      while its mechanisms of tumorigenesis remain poorly characterized. In this study,
      we applied RNA-seq and microRNA-seq methodologies in four pairs of cancer and
      adjacent normal tissues to profile the contribution of miRNAs to tumorigenesis
      altered functional pathways by constructing a comprehensive miRNA-mediated mRNA
      regulatory network. There were 213 differentially expressed (DE) miRNAs and 2172
      DE mRNAs with the involvement of negative miRNA-mRNA interactions identified by
      at least two pairs of cancerous tissues. GO analysis revealed that the
      upregulated microRNAs significantly contributed to a global down-regulation of a
      number of transcription factors (TFs) in OSCC. Among the negative regulatory
      networks between the selected miRNAs (133) and TFs (167), circadian rhythm genes
      (RORA, RORB, RORC, and CLOCK) simultaneously regulated by multiple microRNAs were
      of particular interest. For instance, RORA transcript was predicted to be
      targeted by 25 co-upregulated miRNAs, of which, miR-503-5p, miR-450b-5p, miR-27a
      3p, miR-181a-5p and miR-183-5p were further validated to directly target RORA,
      resulting in a stronger effect on RORA suppression together. In addition, we
      showed that the mRNA and protein expression levels of RORalpha were significantly
      decreased in most OSCC samples, associated with advanced clinical stage and poor
      prognosis. RORalpha significantly suppressed the proliferation of OSCC cells in
      vitro and in vivo. Attenuated RORalpha decreased p53 protein expression and
      suppressed p53 phosphorylation activity. Altogether, our results strongly suggest
      the importance of the role of miRNAs in regulating the activity of circadian
      rhythm-related TFs network during OSCC tumorigenesis, and provide further clues
      to understand the clinical link between circadian rhythm and cancer therapy.

PMID- 30293996
TI  - A minority-group of renal cell cancer patients with high infiltration of CD20+B
      cells is associated with poor prognosis.
AB  - BACKGROUND: The role of B-lymphocytes in solid tumours is unclear. Tumour biology
      studies have implied both anti- and pro-tumoural effects and prognostic studies
      have mainly linked B-cells to increased survival. This study aimed to analyse the
      clinical relevance of B-lymphocytes in renal cell cancer (RCC), where information
      on the prognostic impact is lacking. METHODS: Following immunohistochemistry
      (IHC) stainings with a CD20 antibody, density of CD20+ B-cells was quantified in
      an RCC discovery- and validation cohort. Associations of B-cell infiltration,
      determined by CD20 expression or a B-cell gene-signature, and survival was also
      analysed in 14 publicly available gene expression datasets of cancer, including
      the kidney clear cell carcinoma (KIRC) dataset. RESULTS: IHC analyses of the
      discovery cohort identified a previously unrecognised subgroup of RCC patients
      with high infiltration of CD20+ B-cells. The B-cell-high subgroup displayed
      significantly shorter survival according to uni- and multi-variable analyses. The
      association between poor prognosis and high density of CD20+ B-cells was
      confirmed in the validation cohort. Analyses of the KIRC gene expression dataset
      using the B-cell signature confirmed findings from IHC analyses. Analyses of
      other gene expression datasets, representing 13 different tumour types, indicated
      that the poor survival-association of B-cells occurred selectively in RCC.
      CONCLUSION: This exploratory study identifies a previously unrecognised poor
      prognosis subset of RCC with high density of CD20-defined B-cells.

PMID- 30293997
TI  - Ovarian tumours of different histologic type and clinical stage induce similar
      changes in lipid metabolism.
AB  - BACKGROUND: Previous results obtained from serum samples of late-stage, high
      grade serous ovarian carcinoma patients showed large alterations in lipid
      metabolism. To validate and extend the results, we studied lipidomic changes in
      early-stage ovarian tumours. In addition to serous ovarian cancer, we
      investigated whether these changes occur in mucinous and endometrioid
      histological subtypes as well. METHODS: Altogether, 354 serum or plasma samples
      were collected from three centres, one from Germany and two from Finland. We
      performed lipidomic analysis of samples from patients with malignant (N = 138) or
      borderline (N = 25) ovarian tumours, and 191 controls with benign pathology.
      These results were compared to previously published data. RESULTS: We found 39
      lipids that showed consistent alteration both in early- and late-stage ovarian
      cancer patients as well as in pre- and postmenopausal women. Most of these
      changes were already significant at an early stage and progressed with increasing
      stage. Furthermore, 23 lipids showed similar alterations in all investigated
      histological subtypes. CONCLUSIONS: Changes in lipid metabolism due to ovarian
      cancer occur in early-stage disease but intensify with increasing stage. These
      changes occur also in other histological subtypes besides high-grade serous
      carcinoma. Understanding lipid metabolism in ovarian cancer may lead to new
      therapeutic and diagnostic alternatives.

PMID- 30293999
TI  - Treating cue-reactivity with brain stimulation: a new (transdiagnostic) approach.

PMID- 30294000
TI  - Sex differences in schizophrenia: estrogen and mitochondria.

PMID- 30293998
TI  - Glucose homeostasis dependency on acini-islet-acinar (AIA) axis communication: a
      new possible pathophysiological hypothesis regarding diabetes mellitus.
AB  - Studies have highlighted the existence of two intra-pancreatic axes of
      communication: one involved in the regulation of enzyme production by insulin-the
      insular-acinar axis; and another involved in the regulation of insulin release by
      pancreatic enzymes-the acini-insular axis. Previous studies by our laboratory
      show that pancreatic enzymes can affect blood glucose homeostasis and insulin
      secretion independently of their digestive functions, both from the gut lumen and
      probably from the blood. As a result we would like to introduce here the concept
      of acini-islet-acinar (AIA) axis communication (feedback), which could play an
      important role in the development of obesity and diabetes type 2. The AIA
      feedback links the endocrine and exocrine parts of the pancreas and emphasizes
      the essential role that the pancreas plays, as a single organ, in the regulation
      of glucose homeostasis by amylase most probably in gut epithelium and by insulin
      and glucagon in peripheral blood.

PMID- 30294001
TI  - An emerging epigenetic framework of systemic and central mechanisms underlying
      stress-related disorders.

PMID- 30294002
TI  - Publisher Correction: Exosomes maintain cellular homeostasis by excreting harmful
      DNA from cells.
AB  - This Article contains errors in Fig. 4. In panel d, the lanes of the western blot
      should have been labeled '1.05','1.06, '1.09', '1.11' '1.13', '1.16', '1.19',
      '1.22', '1.24', '1.25'. The correct version of Figure 4 appears in the associated
      Publisher Correction.

PMID- 30294004
TI  - SEC Separation of Polysaccharides Using Macroporous Spherical Silica Gel as a
      Stationary Phase.
AB  - Abstract: Meso- and macroporous spherical silica gels of pore sizes in the range
      of 60-1000 A and 40-75 um particle size were investigated as a stationary phase
      for the separation and purification of polysaccharides and poly(ethylene glycols)
      (PEGs) of various MWs using an aqueous mobile phase. Sephadex and Bio-Gel were
      used for comparison as the most common stationary phases for similar purposes.
      The separation of dextrans of a mean MW = 31 kDa from small molecules (NaCl) was
      possible with SiO2 with a pore size of 60-300 A, but the observed efficiencies of
      a column of the same size were lower comparing with Sephadex or Bio-Gel. In the
      case of oxidized alginic acid only SiO2 of the 60 A pore size was suitable, while
      Sephadex, Bio-Gel and other investigated silicas were not efficient. Sephadex and
      300-1000 A SiO2 offered the possibility of dividing dextrans with MW within the
      range of 1 MDa-10 kDa into fractions of various MWs, while Bio-Gel and 60 A SiO2
      were not suitable. The investigated silica gels strongly adsorbed PEGs of MW 2-20
      kDa. The amount adsorbed decreased with the increase of pore size and they were
      not useful as a stationary phase for this class of polymers. An advantage of SiO2
      of the investigated particle size was a very low back pressure comparing with
      Sephadex. A considerably lower price of silica offers time- and cost-efficient
      separation of polysaccharides. Graphical Abstract: 

PMID- 30294005
TI  - Malaria and Early African Development: Evidence from the Sickle Cell Trait.
AB  - We examine the effect of malaria on economic development in Africa over the very
      long run. Using data on the prevalence of the mutation that causes sickle cell
      disease, we measure the impact of malaria on mortality in Africa prior to the
      period in which formal data were collected. Our estimate is that in the more
      afflicted regions, malaria lowered the probability of surviving to adulthood by
      about ten percentage points, which is twice the current burden of the disease.
      The reduction in malaria mortality has been roughly equal to the reduction in
      other causes of mortality. We then ask whether the estimated burden of malaria
      had an effect on economic development in the period before European contact.
      Using data at the ethnic group level, we find little evidence of a negative
      relationship between malaria burden and population density or other measures of
      development.

PMID- 30294003
TI  - Movies promote tobacco use amongst adolescents: The need for policies to prevent
      this phenomenon.
AB  - Tobacco use is the primary preventable cause of death and disability in the
      world. To combat the tobacco epidemic, most countries have signed and ratified
      the World Health Organzation's Framework Convention on Tobacco Control (WHO
      FCTC). Article 13 of this treaty requires implementation of a comprehensive ban
      on tobacco advertising, promotion and sponsorship. Implementation guidelines for
      Article 13 recognize that the depiction of tobacco use in commercially-produced
      films promotes tobacco use amongst young people. In this article we review the
      relationship between the tobacco industry and the movie industry over the past
      100 years; the cross sectional and longitudinal studies that demonstrate a causal
      relationship between exposure to movie smoking depictions and youth smoking
      initiation; and the policy interventions recommended by the WHO to limit youth
      exposure to tobacco in movies.

PMID- 30294006
TI  - Improving Performance and Retention in Introductory Biology with a Utility-Value
      Intervention.
AB  - One way to encourage performance and persistence in STEM fields is to have
      students write about the utility value (UV) or personal relevance of course
      topics to their life. This intervention has been shown to increase engagement and
      performance in introductory courses. However, questions remain about the
      longevity of the effects and how best to implement the intervention in terms of
      dosage and timing. We tested a UV intervention in the first semester of a two
      semester introductory biology sequence. For each of three units across the
      semester, students (N = 577) were randomly assigned to receive either a UV
      writing assignment, in which they explained why course material was useful to
      them personally, or a control assignment, in which they summarized course
      material. This fully crossed design tested the effect of UV dosage level (0, 1,
      2, or 3 UV assignments) as well as the effect of timing (e.g., UV first, control
      first). We found that students exposed to any dosage of UV earned higher grades
      in the course, were more likely to enroll in the second course of the biology
      sequence, and were less likely to abandon their STEM major than students who did
      not receive any UV assignments. In terms of timing, students with a history of
      poor performance benefitted from writing a UV essay in the beginning of the
      semester, whereas higher-performing students benefitted from a UV essay at the
      end of the semester. Recommendations for practice are discussed.

PMID- 30294007
TI  - Interactive effects of herbivory and substrate orientation on algal community
      dynamics on a coral reef.
AB  - Herbivory is a significant driver of algal community dynamics on coral reefs.
      However, abiotic factors such as the complexity and orientation of the benthos
      often mediate the impact of herbivores on benthic communities. We experimentally
      evaluated the independent and interactive effects of substrate orientation and
      herbivorous fishes on algal community dynamics on a coral reef in the Florida
      Keys, USA. We created horizontal and vertical substrates, mimicking the trend in
      the reduction of vertical surfaces of coral reefs, to assess how algal
      communities developed either with herbivory (open areas) or without herbivory
      (herbivore exclosures). We found that substrate orientation was the dominant
      influence on macroalgal community composition. Herbivores had little impact on
      community development of vertical substrates as crustose algae dominated these
      substrates regardless of being in exclosures or open areas. In contrast,
      herbivores strongly impacted communities on horizontal substrates, with upright
      macroalgae (e.g., Dictyota spp., articulated coralline algae) dominating
      herbivore exclosures, while filamentous turf algae and sediment dominated open
      areas. Outside of exclosures, differences between vertical and horizontal
      substrates exposed to herbivores persisted despite similar intensity of
      herbivory. Our results suggest that the orientation of the reef benthos has an
      important impact on benthic communities. On vertical surfaces, abiotic factors
      may be more important for structuring algal communities while herbivory may be
      more important for controlling algal dynamics in flatter areas. Thus, the decline
      in structural complexity of Caribbean coral reefs and the flattening of reef
      substrates may fundamentally alter the impact that herbivores have on benthic
      community dynamics.

PMID- 30294008
TI  - Bathyal and abyssal demersal bait-attending fauna of the Eastern Mediterranean
      Sea.
AB  - Baited cameras were deployed over a depth range of 532-5111 m in the Ionian Sea
      to characterise the large mobile fauna. The planned installation of a neutrino
      telescope also offers the potential for biological observatories. The current
      study was intended to aid observatory placement. At increasing depths, sediment
      was observed to become more uniform and animal burrows and tracks reduced. A
      total of 10 species of deep-sea fishes were identified from images; four
      elasmobranchs, which were not recorded deeper than 1841 m, and six teleosts. At
      depths > 3000 m, including Calypso Deep, the deepest point in the Mediterranean,
      only one fish species was observed; the Mediterranean grenadier, Coryphaenoides
      mediterraneus (3400-5111 m), extending this species' maximum recorded depth to
      5111 m. Four species of decapod crustacea could be identified from images. The
      dressed deep-sea shrimp, Acanthephyra eximia (1346-5111 m) was the only
      invertebrate recorded at abyssal depths, including the deepest point. A faunal
      change was detected at ~ 1000 m depth. Incorporating other studies from the
      Eastern Mediterranean identified additional faunal boundaries at ~ 1500 m and ~
      2500 m. The time from landing the observation equipment to the arrival of the
      first fish increased exponentially with depth at a slower rate to that observed
      in the Atlantic Ocean. The estimated density of bait-attending deep-sea fish was,
      therefore, significantly impoverished compared to the Atlantic Ocean at
      equivalent depth. Barriers to colonisation, low resource input, and high
      temperature at depth relative to the Atlantic Ocean are probable causes of the
      impoverished fauna.

PMID- 30294010
TI  - MMPAC Information.

PMID- 30294009
TI  - Short & Sweet: Make Your Mark on November 2014 Election.

PMID- 30294011
TI  - Center for Vaccine Development More Important Now More Than Ever.

PMID- 30294013
TI  - News From Missouri Medicine.

PMID- 30294012
TI  - Doctor's Desk For Next Generation.

PMID- 30294014
TI  - Contributors to the MPHP 2014 Fund Raising Campaign.

PMID- 30294015
TI  - Annual Convention, April 17 - April 19, 2015 ? Westin Crown Center ? Kansas City
      Preliminary Program.

PMID- 30294016
TI  - 2015 Annual Convention General Session Topics & Special Events.

PMID- 30294017
TI  - New Missouri Medicine Editorial Board Member.

PMID- 30294018
TI  - Near-Death Experiences.

PMID- 30294019
TI  - News from Missouri Medicine.

PMID- 30294021
TI  - Missouri Physicians Health Foundation 2014.

PMID- 30294020
TI  - Missouri State Medical Association Balance Sheet 2014.

PMID- 30294022
TI  - The Retirement Doc's Quiz.

PMID- 30294023
TI  - New Book Compiles Writings by Arthur Gale, MD.

PMID- 30294024
TI  - Missouri Medicine in the News.

PMID- 30294025
TI  - Meet MSMA's 2015-2016 President.

PMID- 30294027
TI  - Recipients of the 50-Year Physician Pin.

PMID- 30294026
TI  - Sue Ann Greco to Lead Medical Alliance.

PMID- 30294028
TI  - House of Delegates Votes on Resolutions.

PMID- 30294029
TI  - Awards: Arthur Gale Freedom of Expression.

PMID- 30294030
TI  - Sponsors & Exhibit Partners.

PMID- 30294031
TI  - Summary of Council Actions: 2014-2015.

PMID- 30294032
TI  - Reports of the Delegate Handbook: 2014-2015.

PMID- 30294033
TI  - MSMA Elects Leadership.

PMID- 30294034
TI  - 2015 Annual Convention Attendance.

PMID- 30294035
TI  - Sexual and Gender Minority Identity Disclosure During Undergraduate Medical
      Education: "In the Closet" in Medical School: MEDSCAPE 2/18/2015.
AB  - Overview: Of sexual minority respondents, 29.5% said they concealed their sexual
      identify in medical school. Although most (67.5%) were "out" about their
      identity, the authors note that this is not all that much better than the
      estimate of 44% 2 decades ago. (Some respondents declined to answer this
      question).Sexual identity concealment was lowest among gay and lesbian (14.7%)
      and queer (22.2%) respondents. Most bisexuals (53.9%) and questioning (92.0%)
      respondents reported concealing their sexual identify in medical school. Purpose:
      To assess identity disclosure among sexual and gender minority (SGM) students
      pursuing undergraduate medical training in the United States and Canada. Method:
      From 2009 to 2010, a survey was made available to all medical students enrolled
      in the 176 MD-and DO-granting medical schools in the United States and Canada.
      Respondents were asked about their sexual and gender identity, whether they were
      "out" (i.e., had publicly disclosed their identity), and, if they were not, their
      reasons for concealing their identity. The authors used a mixed-methods approach
      and analyzed quantitative and qualitative survey data. Results: Of 5,812
      completed responses (of 101,473 eligible respondents; response rate 5.7%), 920
      (15.8%) students from 152 (of 176; 86.4%) institutions identified as SGMs. Of the
      912 sexual minorities, 269 (29.5%) concealed their sexual identity in medical
      school. Factors associated with sexual identity concealment included sexual
      minority identity other than lesbian or gay, male gender, East Asian race, and
      medical school enrollment in the South or Central regions of North America. The
      most common reasons for concealing one's sexual identity were "nobody's business"
      (165/269; 61.3%), fear of discrimination in medical school (117/269; 43.5%), and
      social or cultural norms (110/269; 40.9%). Of the 35 gender minorities, 21
      (60.0%) concealed their gender identity, citing fear of discrimination in medical
      school (9/21; 42.9%) and lack of support (9/21; 42.9%). Conclusions: SGM students
      continue to conceal their identity during undergraduate medical training. Medical
      institutions should adopt targeted policies and programs to better support these
      individuals.

PMID- 30294036
TI  - Former Missouri Medicine Editor Jordan W. Burkey, MD, Dies: Dr. Burkey was Editor
      of the MSMA Journal from 1982-1988.

PMID- 30294037
TI  - Physician of the Day.

PMID- 30294038
TI  - Get to Know Your Physician Legislators.

PMID- 30294039
TI  - BEWARE: Tax Identity Theft Scam Targets Physicians Again.

PMID- 30294040
TI  - MSMA Members in the News.

PMID- 30294041
TI  - 1 Picture = 1,000 Words.

PMID- 30294042
TI  - Welcome New Members!: (Joined before December 8, 2015).

PMID- 30294043
TI  - It's Important To Be 'Well-versed" About the Panniculus.

PMID- 30294044
TI  - Missouri State Medical Association Alliance Holiday Sharing Card.

PMID- 30294045
TI  - 158th Missouri State Medical Association, March 18-20, 2016 ? St. Louis
      Renaissance Airport Hotel.

PMID- 30294046
TI  - Missouri State Medical Association, 158th Annual Convention, March 18-20, 2016 |
      St. Louis Renaissance Airport Hotel.

PMID- 30294047
TI  - Discussion of Laber et al. "Optimal treatment allocations in space and time for
      on-line control of an emerging infectious disease".

PMID- 30294048
TI  - Aerobic oxidation of alcohols in visible light on Pd-grafted Ti cluster.
AB  - The titanium cluster with the reduced band gap has been synthesized having the
      palladium nanoparticles over the surface, which not only binds to the atmospheric
      oxygen but also catalyzes the oxidation of alcohols under visible light.

PMID- 30294049
TI  - Scale of Small Particle Population in Activated Sludge Flocs.
AB  - The light scattering method is a valuable tool for accessing particle size and
      structure mainly due to fast and the nonintrusive nature of the measurement. The
      method is based on a scattered intensity pattern and depends on particle volume,
      particle morphology, the light wavelength and the scattering angle. The light
      scattering model, for particles characterised by a fractal structure, is enabled
      with the use of the Rayleigh-Gans-Debye theory under constrained assumptions. The
      range of validity of the Rayleigh-Gans-Debye is limited when primary particles
      constituting aggregate have a size close to the wavelength. In this work, a range
      of particle sizes was characterised in order to achieve a better understanding of
      the relationship between flocs size and its fractal dimension. Hence, the width
      of the power law regime is discussed. What is more, a specific fractal dimension
      value of activated sludge flocs was found for each of the analysed wastewater
      treatment plant, which suggests that the spatial structure of suspensions
      constituting the activated sludge is an individual characteristic of each
      treatment facility. It has been shown that activated sludge consists of
      microflocs from the range of 1-10 MUm, which constitute approximately 90% of all
      the population.

PMID- 30294050
TI  - ASSESSING ROBUSTNESS OF CLASSIFICATION USING ANGULAR BREAKDOWN POINT.
AB  - Robustness is a desirable property for many statistical techniques. As an
      important measure of robustness, breakdown point has been widely used for
      regression problems and many other settings. Despite the existing development, we
      observe that the standard breakdown point criterion is not directly applicable
      for many classification problems. In this paper, we propose a new breakdown point
      criterion, namely angular breakdown point, to better quantify the robustness of
      different classification methods. Using this new breakdown point criterion, we
      study the robustness of binary large margin classification techniques, although
      the idea is applicable to general classification methods. Both bounded and
      unbounded loss functions with linear and kernel learning are considered. These
      studies provide useful insights on the robustness of different classification
      methods. Numerical results further confirm our theoretical findings.

PMID- 30294052
TI  - Sentence interpretation by typically developing Vietnamese-English bilingual
      children.
AB  - We examined developing bilinguals' use of animacy and word order cues during
      sentence interpretation tasks administered in each of their languages.
      Participants were 6- to 8-year-old children who learned Vietnamese as a first
      language and English as a second language (n = 23). Participants listened to
      simple sentences and identified the agent or "doer" of the action. English-only
      peers (n = 23) served as a comparison group. Results indicated that the bilingual
      group relied more on animacy than the English-only group when interpreting
      sentences in English and that the bilingual group used a blending or
      "amalgamation" of cues to interpret English and Vietnamese sentences. Significant
      within-group variation in cue preference was investigated as a function of age
      and proficiency in the first language and second language.

PMID- 30294053
TI  - A longitudinal analysis of sentence interpretation in bilingual children.
AB  - This longitudinal study used sentence interpretation tasks to consider growth in
      language processing among school-aged children learning Vietnamese and English.
      Thirty-two children participated yearly over three time points. Children were
      asked to identify the agent of sentences that manipulated linguistic cues
      relevant to Vietnamese (animacy) and English (word order). Hierarchical linear
      modeling was used to examine change in cue use over time as well as the relation
      between cue use and proficiency in each language. Findings include exclusive
      reliance on word order by the end point, nearly identical group-level cue-use
      patterns across languages with individual variation, and positive relationships
      between language proficiency and cue use. Findings are discussed within the
      unified competition model (MacWhinney, 2004) and the literature on sequential
      bilingualism.

PMID- 30294051
TI  - Climate Migration at the Height and End of the Great Mexican Emigration Era.
AB  - Previous research has linked increasing climate-change-related variability to
      Mexico-US migration, but only under particular climatic/social conditions and
      periods of high irregular migration. Using the 2000 and 2010 Mexican censuses, we
      examine this environment-migration nexus across a broader set of socioecological
      contexts and during periods of both increasing (1995-1999) and declining (2005
      2009) migration. Consistent with the notion that climate can "trap" populations
      in place, we find that frequent/severe bouts of hot or dry conditions are
      associated with lower US-bound migration from most of rural Mexico. However, we
      do find higher climate outmigration during episodes hot and dry climate, or out
      of places with lower vulnerability. Our comparisons across periods suggest that
      climate migration is affected by conditions in the U.S. in a similar or slightly
      weaker manner as other forms of migration are. Altogether, our findings suggest
      that rural Mexico is unlikely to push large numbers of international "climate
      refugees" and that climate migration is indeed sensitive to conditions in sending
      and destination areas.

PMID- 30294054
TI  - Modeling Heterogeneity in Healthcare Utilization Using Massive Medical Claims
      Data.
AB  - We introduce a modeling approach for characterizing heterogeneity in healthcare
      utilization using massive medical claims data. We first translate the medical
      claims observed for a large study population and across five years into
      individual-level discrete events of care called utilization sequences. We model
      the utilization sequences using an exponential proportional hazards mixture model
      to capture heterogeneous behaviors in patients' healthcare utilization. The
      objective is to cluster patients according to their longitudinal utilization
      behaviors and to determine the main drivers of variation in healthcare
      utilization while controlling for the demographic, geographic, and health
      characteristics of the patients. Due to the computational infeasibility of
      fitting a parametric proportional hazards model for high-dimensional, large
      sample size data we use an iterative one-step procedure to estimate the model
      parameters and impute the cluster membership. The approach is used to draw
      inferences on utilization behaviors of children in the Medicaid system with
      persistent asthma across six states. We conclude with policy implications for
      targeted interventions to improve adherence to recommended care practices for
      pediatric asthma.

PMID- 30294055
TI  - Accounting for non-response bias using participation incentives and survey
      design: An application using gift vouchers.
AB  - Standard corrections for missing data rely on the strong and generally untestable
      assumption of missing at random. Heckman-type selection models relax this
      assumption, but have been criticized because they typically require a selection
      variable which predicts non-response but not the outcome of interest, and can
      impose bivariate normality. In this paper we illustrate an application using a
      copula methodology which does not rely on bivariate normality. We implement this
      approach in data on HIV testing at a demographic surveillance site in rural South
      Africa which are affected by non-response. Randomized incentives are the ideal
      selection variable, particularly when implemented ex ante to deal with potential
      missing data. However, elements of survey design may also provide a credible
      method of correcting for non-response bias ex post. For example, although not
      explicitly randomized, allocation of food gift vouchers during our survey was
      plausibly exogenous and substantially raised participation, as did effective
      survey interviewers. Based on models with receipt of a voucher and interviewer
      identity as selection variables, our results imply that 37% of women in the
      population under study are HIV positive, compared to imputation-based estimates
      of 28%. For men, confidence intervals are too wide to reject the absence of non
      response bias. Consistent results obtained when comparing different selection
      variables and error structures strengthen these conclusions. Our application
      illustrates the feasibility of the selection model approach when combined with
      survey metadata.

PMID- 30294056
TI  - A Two-Scale Model of Radio-Frequency Electrosurgical Tissue Ablation.
AB  - Radio-frequency electrosurgical procedures are widely used to simultaneously
      dissect and coagulate tissue. Experiments suggest that evaporation of cellular
      and intra-cellular water plays a significant role in the evolution of the
      temperature field at the tissue level, which is not adequately captured in a
      single scale energy balance equation. Here, we propose a two-scale model to study
      the effects of microscale phase change and heat dissipation in response to
      radiofrequency heating on the tissue level in electrosurgical ablation
      procedures. At the microscale, the conservation of mass along with thermodynamic
      and mechanical equilibrium is applied to obtain an equation-of-state (EOS)
      relating vapor mass fraction to temperature and pressure. The evaporation losses
      are incorporated in the macro-level energy conservation and results are validated
      with mean experimental temperature distributions measured from electrosurgical
      ablation testing on ex vivo porcine liver at different power settings of the
      electrosurgical instrument. Model prediction of water loss and its effect on the
      temperature along with the effect of the mechanical properties on results are
      evaluated and discussed.

PMID- 30294057
TI  - The Big Five, Everyday Contexts and Activities, and Affective Experience.
AB  - Prior research shows that personality traits predict time spent with different
      people and frequency of engagement in different activities. Further, personality
      traits, company, and activity are related to the experience of affect. However,
      little research has examined personality, context, and affect together in the
      same study. In the current study, 78 people described their Big Five traits and
      took part in a 1-week experience sampling study using mobile phones as a means
      for data collection. Participants indicated their current company, activity, and
      momentary affect along the dimensions of energetic arousal (EA), tense arousal
      (TA), and hedonic tone (HT). Poisson regressions revealed that traits predicted
      higher frequencies of trait-consistent contexts: for example, extraversion was
      related to more frequently being with various types of company. Results
      predicting contexts from multilevel logistic regressions were sparser. Multilevel
      models revealed that traits and contexts had main effects on affect, yet there
      were relatively few interactions of traits X contexts predicting affect. We
      discuss more specific implications of these findings.

PMID- 30294058
TI  - Investigation of Chiral Recognition by Molecular Micelles with Molecular Dynamics
      Simulations.
AB  - Molecular dynamics simulations were used to characterize the binding of the
      chiral drugs chlorthalidone and lorazepam to the molecular micelle poly-(sodium
      undecyl-(L)-leucine-valine). The project's goal was to characterize the nature of
      chiral recognition in capillary electrophoresis separations that use molecular
      micelles as the chiral selector. The shapes and charge distributions of the
      chiral molecules investigated, their orientations within the molecular micelle
      chiral binding pockets, and the formation of stereoselective intermolecular
      hydrogen bonds with the molecular micelle were all found to play key roles in
      determining where and how lorazepam and chlorthalidone enantiomers interacted
      with the molecular micelle.

PMID- 30294059
TI  - When equity matters for marital stability: Comparing German and U.S. couples.
AB  - Comparing West Germany and the United States, we analyze the association between
      equity - in terms of the relative gender division of paid and unpaid work hours -
      and the risk of marriage dissolution. Our aim is to identify under what
      conditions equity influences couple stability. We apply event-history analysis to
      marriage histories using data from the German Socio-Economic Panel for Western
      Germany and the Panel Study of Income Dynamics for the United States for the
      period 1986 to 2009. For the United States, we find that deviation from equity is
      particularly destabilizing when the wife under-benefits, and when both partners'
      paid work hours are similar. In West Germany, equity is less salient. Instead we
      find that the male breadwinner model remains the single most stable arrangement.

PMID- 30294060
TI  - Genomic Feature Selection by Coverage Design Optimization.
AB  - We introduce a novel data reduction technique whereby we select a subset of tiles
      to "cover" maximally events of interest in large-scale biological datasets (e.g.,
      genetic mutations), while minimizing the number of tiles. A tile is a genomic
      unit capturing one or more biological events, such as a sequence of base pairs
      that can be sequenced and observed simultaneously. The goal is to reduce
      significantly the number of tiles considered to those with areas of dense events
      in a cohort, thus saving on cost and enhancing interpretability. However, the
      reduction should not come at the cost of too much information, allowing for
      sensible statistical analysis after its application. We envisage application of
      our methods to a variety of high throughput data types, particularly those
      produced by next generation sequencing (NGS) experiments. The procedure is cast
      as a convex optimization problem, which is presented, along with methods of its
      solution. The method is demonstrated on a large dataset of somatic mutations
      spanning 5000+ patients, each having one of 29 cancer types. Applied to these
      data, our method dramatically reduces the number of gene locations required for
      broad coverage of patients and their mutations, giving subject specialists a more
      easily interpretable snapshot of recurrent mutational profiles in these cancers.
      The locations identified coincide with previously identified cancer genes.
      Finally, despite considerable data reduction, we show that our covering designs
      preserve the cancer discrimination ability of multinomial logistic regression
      models trained on all of the locations (> 1M).

PMID- 30294062
TI  - Comments on "Tutorial on statistical considerations on subgroup analysis in
      confirmatory clinical trials".
AB  - This paper is the letter to the editor regarding several comments on 'Tutorial on
      statistical considerations on subgroup analysis in confirmatory clinical trials.'

PMID- 30294061
TI  - Nonlocal low-rank and sparse matrix decomposition for spectral CT reconstruction.
AB  - Spectral computed tomography (CT) has been a promising technique in research and
      clinic because of its ability to produce improved energy resolution images with
      narrow energy bins. However, the narrow energy bin image is often affected by
      serious quantum noise because of the limited number of photons used in the
      corresponding energy bin. To address this problem, we present an iterative
      reconstruction method for spectral CT using nonlocal low-rank and sparse matrix
      decomposition (NLSMD), which exploits the self-similarity of patches that are
      collected in multi-energy images. Specifically, each set of patches can be
      decomposed into a low-rank component and a sparse component, and the low-rank
      component represents the stationary background over different energy bins, while
      the sparse component represents the rest of different spectral features in
      individual energy bins. Subsequently, an effective alternating optimization
      algorithm was developed to minimize the associated objective function. To
      validate and evaluate the NLSMD method, qualitative and quantitative studies were
      conducted by using simulated and real spectral CT data. Experimental results show
      that the NLSMD method improves spectral CT images in terms of noise reduction,
      artifacts suppression and resolution preservation.

PMID- 30294064
TI  - Cine Cardiac MRI Slice Misalignment Correction Towards Full 3D Left Ventricle
      Segmentation.
AB  - Accurate segmentation of the left ventricle (LV) blood-pool and myocardium is
      required to compute cardiac function assessment parameters or generate
      personalized cardiac models for pre-operative planning of minimally invasive
      therapy. Cardiac Cine Magnetic Resonance Imaging (MRI) is the preferred modality
      for high resolution cardiac imaging thanks to its capability of imaging the heart
      throughout the cardiac cycle, while providing tissue contrast superior to other
      imaging modalities without ionizing radiation. However, there exists an
      inevitable misalignment between the slices in cine MRI due to the 2D + time
      acquisition, rendering 3D segmentation methods ineffective. A large part of
      published work on cardiac MR image segmentation focuses on 2D segmentation
      methods that yield good results in mid-slices, however with less accurate results
      for the apical and basal slices. Here, we propose an algorithm to correct for the
      slice misalignment using a Convolutional Neural Network (CNN)-based regression
      method, and then perform a 3D graph-cut based segmentation of the LV using atlas
      shape prior. Our algorithm is able to reduce the median slice misalignment error
      from 3.13 to 2.07 pixels, and obtain the blood-pool segmentation with an accuracy
      characterized by a 0.904 mean dice overlap and 0.56 mm mean surface distance with
      respect to the gold-standard blood-pool segmentation for 9 test cine MR datasets.

PMID- 30294063
TI  - Tumor margin assessment of surgical tissue specimen of cancer patients using
      label-free hyperspectral imaging.
AB  - We are developing label-free hyperspectral imaging (HSI) for tumor margin
      assessment. HSI data, hypercube (x,y,lambda), consists of a series of high
      resolution images of the same field of view that are acquired at different
      wavelengths. Every pixel on the HSI image has an optical spectrum. We developed
      preprocessing and classification methods for HSI data. We used spectral features
      from HSI data for the classification of cancer and benign tissue. We collected
      surgical tissue specimens from 16 human patients who underwent head and neck
      (H&N) cancer surgery. We acquired both HSI, autofluorescence images, and
      fluorescence images with 2-NBDG and proflavine from the specimens. Digitized
      histologic slides were examined by an H&N pathologist. The hyperspectral imaging
      and classification method was able to distinguish between cancer and normal
      tissue from oral cavity with an average accuracy of 90+/-8%, sensitivity of 89+/
      9%, and specificity of 91+/-6%. For tissue specimens from the thyroid, the method
      achieved an average accuracy of 94+/-6%, sensitivity of 94+/-6%, and specificity
      of 95+/-6%. Hyperspectral imaging outperformed autofluorescence imaging or
      fluorescence imaging with vital dye (2-NBDG or proflavine). This study suggests
      that label-free hyperspectral imaging has great potential for tumor margin
      assessment in surgical tissue specimens of H&N cancer patients. Further
      development of the hyperspectral imaging technology is warranted for its
      application in image-guided surgery.

PMID- 30294065
TI  - Family Structure and Child Food Insecurity: Evidence from the Current Population
      Survey.
AB  - Food insecurity-the lack of consistent access to adequate amounts of food-remains
      a reality for many American families. Although children are usually protected
      from reductions in food intake even in households with low food security, about 8
      percent of all households with children also experienced reduced food intake and
      disrupted eating patterns. The research on child food insecurity and family
      structure is limited and the findings are mixed. Given the increasing complexity
      of families in the U.S., combined with sustained high levels of food insecurity
      during the last decade, a closer examination of this relationship is warranted.
      Using data from multiple years of the Current Population Survey Food Security
      Supplement (N=39,619 households) this study finds that children growing up in
      complex family households are more vulnerable to food insecurity, on average,
      than children growing up in two biological married-parent households. The results
      also show higher odds of child food insecurity among single mother households
      than among married biological or married stepfamilies suggesting a protective
      effect of marriage beyond economic resources.

PMID- 30294066
TI  - Irradiation effects in monazite-(Ce) and zircon: Raman and photoluminescence
      study of Au-irradiated FIB foils.
AB  - Lamellae of 1.5 um thickness, prepared from well-crystallised monazite-(Ce) and
      zircon samples using the focused-ion-beam technique, were subjected to triple
      irradiation with 1 MeV Au+ ions (15.6% of the respective total fluence), 4 MeV
      Au2+ ions (21.9%) and 10 MeV Au3+ ions (62.5%). Total irradiation fluences were
      varied in the range 4.5 * 1012 - 1.2 * 1014 ions/cm2. The highest fluence
      resulted in amorphisation of both minerals; all other irradiations (i.e. up to
      4.5 * 1013 ions/cm2) resulted in moderate to severe damage. Lamellae were
      subjected to Raman and laser-induced photoluminescence analysis, in order to
      provide a means of quantifying irradiation effects using these two micro
      spectroscopy techniques. Based on extensive Monte Carlo calculations and
      subsequent defect-density estimates, irradiation-induced spectroscopic changes
      are compared with those of naturally self-irradiated samples. The finding that
      ion irradiation of monazite-(Ce) may cause severe damage or even amorphisation,
      is in apparent contrast to the general observation that naturally self-irradiated
      monazite-(Ce) does not become metamict (i.e. irradiation-amorphised), in spite of
      high self-irradiation doses. This is predominantly assigned to the continuous low
      temperature damage annealing undergone by this mineral; other possible causes are
      discussed. According to cautious estimates, monazite-(Ce) samples of
      Mesoproterozoic to Cretaceous ages have stored only about 1% of the total damage
      experienced. In contrast, damage in ion-irradiated and naturally self-irradiated
      zircon is on the same order; reasons for the observed slight differences are
      discussed. We may assess that in zircon, alpha decays create significantly less
      than 103 Frenkel-type defect pairs per event, which is much lower than previous
      estimates. Amorphisation occurs at defect densities of about 0.10 dpa
      (displacements per lattice atom).

PMID- 30294067
TI  - The influence of lithology on surface water sources.
AB  - Understanding the temporal and spatial variability of water sources within a
      basin is vital to our ability to interpret hydrologic controls on biogeochemical
      processes and to manage water resources. Water stable isotopes can be used as a
      tool to determine geographic and seasonal sources of water at the basin scale.
      Previous studies in the Coastal Range of Oregon reported that the variation in
      the isotopic signatures of surface water did not conform to the commonly observed
      "elevation effect", which exhibits a trend of increasing isotopic depletion with
      rising elevation. The primary purpose of this research is to investigate the
      mechanisms governing seasonal and spatial variations in the isotopic signature of
      surface waters within the Marys River Basin, located in the leeward side of the
      Oregon Coastal Range. Surface water and precipitation samples were collected
      every 2-3 weeks for isotopic analysis for one year. Our results confirmed the
      lack of elevational variation of surface water isotopes within this leeward
      basin. While we find elevational variation in precipitation in the eastern
      portion of the watershed, this elevation effect is counteracted by rainout with
      distance from the Pacific coast. In addition we found significant variation in
      surface water isotope values between catchments underlain predominantly by basalt
      or sandstone. The degree of separation was strongest during the summer when low
      flows reflect deeper groundwater sources. This indicates that baseflow within
      streams drained by each lithology is being supplied from two distinctly separate
      water sources. In addition, the flow of the Marys River is dominated by water
      originating from the sandstone water source, particularly during the low flow
      summer months. We interpreted that the difference in water source results from
      sandstone catchments having highly fractured geology or locally tipping to the
      east facilitating cross-basin water exchange from the windward to the leeward
      side of the Coast Range. Our results challenge topographic derived watershed
      boundaries in permeable sedimentary rocks; highlighting the overwhelming
      importance of underlying geology.

PMID- 30294068
TI  - The impact of culture conditions on growth and metabolomic profiles of freshwater
      cyanobacteria.
AB  - Cultured cyanobacteria produce secondary metabolites with a wide range of
      biological activities and are an important source of natural products. In the
      context of secondary metabolite discovery, microbial culture conditions are
      expected to support optimum growth, induce maximum chemical diversity, and be
      suitable for the majority of cyanobacterial strains. We investigated the effect
      of nitrate and phosphate on biomass production and metabolomic profiles of three
      filamentous freshwater cyanobacterial strains: cf. Oscillatoria sp. UIC 10045,
      Scytonema sp. UIC 10036, and Nostoc sp. UIC 10110. A standardized inoculation
      procedure allowed for the assessment of cell mass production. Dried
      cyanobacterial cell mass was extracted and analyzed by liquid chromatography
      coupled with high resolution mass spectrometry (UPLC-HRMS), followed by
      comparative metabolomics analysis using XCMS Online. Results showed that low
      nitrate media significantly reduced cell mass production for all three strains.
      Low nitrate also induced production of primary metabolites (heterocyst
      glycolipids) in strains UIC 10036 and UIC 10110. Changes in phosphate levels
      affected each strain differently. Strain UIC 10110 showed a significant increase
      in production of merocyclophane C when cultivated in low phosphate, while strain
      UIC 10036 displayed higher production of tolytoxin under high phosphate.
      Additionally, these experiments led to the identification of a potentially new
      peptide produced by strain UIC 10036.

PMID- 30294069
TI  - Color Doppler ultrasonography targeted reconstruction using pedicled perforator
      flaps-a systematic review and meta-analysis.
AB  - Background: Flaps are increasingly popularized in reconstructive surgery and
      there is need to test and increase their reliability. Color Doppler ultrasound
      has been stated to be valuable in flap planning. The aim of this study was to
      conduct a systematic review and meta-analysis of the literature of Color Doppler
      ultrasound targeted pedicled perforator flaps and provide information on outcomes
      and complication rates. Method: A systematic review and meta-analysis were
      conducted for articles published until April 2017 in PubMed and Embase. We aimed
      to include randomized clinical trials, meta-analysis, prospective studies, case
      control studies, and cohort studies written in English. We included studies where
      CDU was used to identify the perforator(s) prior to surgery. We evaluated the
      quality of the included studies using checklists recommended by the Cochrane
      group. Results: From the initial 219 studies, only 12 studies using Color Doppler
      targeted pedicled perforator flaps in 252 cases met the inclusion and exclusion
      criteria. Eleven of these were case series and one a prospective study. The
      incidence of major complications was 8% (21/252) and minor complications was 14%,
      comprising of mostly necrosis 8% (24/252) and venous congestion 8% (21/252).
      Conclusions: The reconstructive success rate following pedicled perforator flap
      reconstruction targeted by CDU appears to be high and the procedure provides a
      wide scope of applications and margin of safety. It is evident that the risk of
      venous congestion is 11 times greater in the lower extremities than the truncus,
      a finding that needs further attention in future studies.Level of Evidence: Level
      IV, risk/prognostic study.

PMID- 30294070
TI  - Poly Implant Prothese silicone breast implants: implant dynamics and capsular
      contracture.
AB  - Background: The Poly Implant Prothese (PIP) implants were withdrawn from the
      market in 2010 due to the use of low-grade silicone, causing a high risk for
      implant rupture. The aim of this study was to investigate the implant dynamics of
      PIP breast implants, as well as to determine the rate and predictors of implant
      gel bleeding, rupture, and capsular contracture in PIP implants. Methods: Eighty
      women with a total of 152 PIP implants who underwent a reoperation in 2012 were
      enrolled in this study. Physical investigation included assessing the Baker score
      and demographics were retrospectively traced in medical records. The pre- and
      post-operative volumes of the implants were calculated and their state was
      determined intraoperatively by the surgeon. Results: The implants were removed
      after a mean implant duration of 11 +/- 2.1 years. Gel bleed and implant rupture
      occurred in respectively 42 and 25% of the implants. Intact implants had post
      operative volume increase as well as decrease. There was a correlation between
      gel bleeding and more post-operative implant volume increase (P <= 0.05).
      Capsular contracture had a protective effect against post-operative implant
      volume increase (P <= 0.05), while a post-operative implant volume increase
      provided a protective influence in developing capsular contracture (P <= 0.05).
      Additionally, implant rupture led to a higher risk of capsular contracture (P <=
      0.05). Conclusions: We managed to illustrate that PIP implant shells were too
      permeable and that there is a correlation between gel bleeding and the increase
      of the post-operative implant volume. Implant rupture led to a higher risk for
      developing capsular contracture.Level of evidence: Level III, risk / prognostic
      study.

PMID- 30294071
TI  - Applications and limitations of using patient-specific 3D printed molds in
      autologous breast reconstruction.
AB  - Background: Over the last years, several techniques have been proposed to improve
      the outcome of autologous breast reconstruction procedures. One of these
      innovations describes patient-specific, three-dimensional (3D) printed breast
      molds for intraoperative use based on 3D stereophotogrammetry. In this article,
      we want to share our preliminary experiences with producing such templates, its
      clinical possibilities and limitations in practice. Methods: Patient-specific
      templates were designed based on 3D stereophotogrammetry images. The 3D template
      was fabricated using a 3D printer. During breast reconstruction, the autologous
      flap was placed inside the printed template to aid the surgeon in determining the
      shape and volume of the autologous flap creating the desired breast dimensions.
      Patients were 3D-photographed 6 to 9 months post-operatively. Results: Three
      patients with unilateral breast reconstructions showed a width difference of 0.5
      cm and mean volume difference of 211 ml between the reconstructed and
      contralateral breasts. In the three bilateral reconstructed patients, a mean
      difference in breast width and volume of respectively 0.5 cm and 16 ml was found.
      Conclusions: Patient-specific breast templates are inexpensive and relatively
      easy to design, while being practical and convenient to obtain insight in the
      dimensions of the desired breast during reconstruction, according to the
      operating surgeons. Patient selection is however critical, as patients must have
      sufficient donor volume and/or satisfying breast shape to be able to use the
      template to its full potential.Level of evidence: Level IV, therapeutic study.

PMID- 30294072
TI  - Integrated emergy and economic evaluation of lotus-root production systems on
      reclaimed wetlands surrounding the Pearl River Estuary, China.
AB  - Lotus (Newnbo nucifera, Gaertn) is the most important aquatic vegetable in China,
      with a cultivation history of over 3000 years. The emergy, energy, material, and
      money flows of three lotus root cultivation modes in Wanqingsha, Nansha District,
      Guangzhou, China were examined using Energy Systems Language models and emergy
      evaluation to better understand their ecological and economic characteristics on
      multiple spatial and temporal scales. The natural resource foundations, economic
      characteristics and sustainability of these modes were evaluated and compared.
      The results showed that although all three modes were highly dependent on
      purchased emergy inputs, their potential impacts as measured by the local (ELRL)
      and global (ELRW) environmental loading ratios were less than 1.2 and 0.7,
      respectively. The lotus-fish mode was the most sustainable with its emergy index
      of sustainable development (EISD) 2.09 and 2.13 times that of the pure lotus and
      lotus-shrimp modes, respectively. All three lotus-root production modes had
      superior economic viability, since their Output/Input ratio ranged from 2.56 to
      4.95. The results indicated that agricultural systems may have different
      environmental impacts and sustainability characteristics at different spatial and
      temporal scales, and that these impacts and characteristics can be simultaneously
      explored using integrated emergy and economic evaluations.

PMID- 30294073
TI  - CYCLIC SULFONE-3-CARBOXAMIDES AS NOVEL P2-LIGANDS FOR Ro 31-8959 BASED HIV-1
      PROTEASE INHIBITORS.
AB  - Cyclic sulfone-3-carboxamides are effective P2-1igands for HIV-1 protease
      inhibitors. Incorporation of 3S-tetrahydro-2H-thiopyrancarboxamide-l, l-dioxide
      in the hydroxyethylamine series resulted in inhibitor 14 (IC50=9 nM, CIC95=200
      nM) with improved potency compared to its corresponding urethane derivative 18
      (IC50=2.0 MUM).

PMID- 30294074
TI  - Changing Tides: Mothers' Supportive Emotion Socialization Relates Negatively to
      Third-Grade Children's Social Adjustment in School.
AB  - Parents' supportive reactions to children's negative emotions are thought to
      promote children's social adjustment. Research heretofore has implicitly assumed
      that such reactions are equally supportive of children's adjustment across ages.
      Recent findings challenge this assumption, suggesting that during middle
      childhood, socialization practices previously understood as supportive may in
      fact impede children's social adjustment. We explored this possibility in a
      sample of 203 third-grade children and their mothers. Using structural equation
      modeling, we tested associations between mothers' supportive (i.e., problem- and
      emotion-focused) reactions to children's negative emotions and children's social
      skills and problems as reported by mothers and teachers. Mothers' supportive
      reactions predicted greater social adjustment in children as reported by mothers.
      Inverse associations, however, were found with teachers' reports of children's
      social adjustment: mothers' supportive reactions predicted fewer socioemotional
      skills and more problem behaviors. These contrasting patterns suggest potential
      unperceived costs associated with mothers' supportiveness of children's negative
      emotions for third-grade children's social adjustment in school and highlight the
      importance of considering associations between socialization practices and
      children's various social contexts. The findings also highlight a need for
      greater consideration of what supportiveness means across different developmental
      periods.

PMID- 30294075
TI  - Challenges to Healthcare in India - The Five A's.

PMID- 30294076
TI  - Capacity Building of Private Sector Workforce for Public Health Services in
      India: Scope and Challenges.
AB  - Indian health sector is a complex admixture of public and private providers, but
      several lacunae of public health service delivery system in terms of human
      resource, access, and quality have resulted in unprecedented growth of private
      sector. Although seamless delivery of services at rural and urban areas, timely
      approach, and improved information technology system are the strength of the
      private sector, this package comes at the cost of high out-of-pocket expenditure.
      Mobilization of private sector health workforce by their capacity building in
      terms of orientation toward public health services is one of the available
      solutions to move toward wider coverage of public health services. However,
      numerous challenges need to be addressed before realization of this vision.

PMID- 30294077
TI  - Assessment of Functioning of Village Health Nutrition and Sanitation Committees
      in a District in Maharashtra.
AB  - Background: Community participation is one of the core principles of primary
      healthcare. The village health nutrition and sanitation committee (VHNSC), one of
      the elements in implementation of the National Health Mission (NHM), is an
      example of community participation. There are not many studies conducted to
      assess the actual participation of VHNSC in health-care delivery at the village
      level. Objective: The objective of the study is to develop a VHNSC Maturity Index
      (VMI) and pilot it to assess the institutional maturity of VHNSC. Materials and
      Methods: This community-based, cross-sectional study was conducted in 83 villages
      under four Primary Health Centres (PHCs) of the Wardha Community Development
      block. VMI was developed, Through several discussion sessions with VHNSC members
      and staff of the DCM; observations of VHND; attending VHNSC monthly meetings; the
      VMI was finalized after piloting it in all the four PHC areas. Results: All the
      83 VHNSCs were constituted as per norms led down under NHM. Forty-eight (57.8%)
      VHNSCs had developed an annual Village Health Action Plan, 72 (86.7%) VHNSCs had
      >=4 meetings held in the past 6 months, and >=70% attendance in the past 6 months
      was observed in 40 (48.2%) VHNSCs. A majority of 82 (98.8%) VHNSCs helped in
      organizing the village health and nutrition day, 59 (71.1%) VHNSCs monitored the
      implementation of national health programs. The entire untied fund received in
      the previous year was utilized by 68 (81.9%) VHNSCs. Conclusion: The study shows
      that VMI can be used for continuous monitoring and assessment tool for VHNSC to
      evaluate and plan different health activities.

PMID- 30294078
TI  - India has Reached on the Descending Limb of Tobacco Epidemic.
AB  - Introduction: Till 2016, India was the second largest consumer of tobacco in the
      world, second only to China. However, in June 2017, the factsheet release of
      Global Adult Tobacco Survey-2 showed a 6% point decline in the prevalence of
      tobacco use among adults (>15 years) in the country. Materials and Methods: This
      is a form of ecological study where trends in aggregate prevalence of tobacco use
      at country level (using secondary data) were studied in relation to corresponding
      policy actions over a period of two decades. Results: The results have shown that
      initial policy actions since the cigarettes act of 1975 till prevention of food
      adulteration Amendment act of 1995 were largely targeting cigarettes, and so
      smoking prevalence among men was constantly declining. On the other hand,
      smokeless tobacco use was increasing among both men and women and reached a peak
      in 2009-2010. After that, the government took strict policy actions including
      Food Safety and Standards Authority of India Gutka ban in 2011. There were other
      persistent efforts, which are discussed in this paper. As a result, a transition
      has occurred in relation to tobacco epidemic in India. Conclusion: The paper has
      been concluded with a note that there is no room for complacence and we have a
      noncommunicable disease action goal to further decline the prevalence of tobacco
      use in the country to <24.22% by the year 2025.

PMID- 30294079
TI  - An Epidemiological Study of Blood Pressure and Its Relation with Anthropometric
      Measurements among Schoolboys of Burdwan Municipal Area, West Bengal.
AB  - Background: High blood pressure (BP) is often an underdiagnosed problem, because
      of the asymptomatic nature in early phases of onset during adolescence. This
      increases the chances of developing complications later during adult life.
      Objective: The objective of this study was to find the relationship of BP with
      anthropometric measurements among school-going adolescent boys. Materials and
      Methods: It was a cross-sectional study conducted among 894 adolescent schoolboys
      aged 13 to 18 years from July 2013 to October 2014 in schools of Burdwan
      Municipal area, West Bengal. The required number of students from each school was
      determined by proportional probability sampling. Then, the required number of
      students from each school was selected by systematic random sampling technique.
      BP and anthropometric measurements such as weight, height, and waist
      circumference were done using standard guidelines. Results: The mean systolic and
      mean diastolic BP in the study participants was significantly higher with an
      increase in weight, height, waist circumference, and body mass index (BMI) (P <
      0.05). BP was found to be positively correlated with different anthropometric
      measurements such as weight, height, waist circumference, and BMI, which were
      statistically significant. Conclusion: Early detection of high BP and application
      of lifestyle modification among adolescents will be helpful in reducing the
      burden of high BP in adult life.

PMID- 30294080
TI  - Relationships between Positive Deviant Behaviors and Children of Normal Growth
      Pattern in Poorly Resourced Rural Communities.
AB  - Background: Promotion of positive deviant behaviors (PDBs) can be crucial to
      bring sustainable change as these behaviors are likely to be affordable and
      acceptable by the wider community. Objectives: The objective of this study was to
      assess if any PDBs exist among poorly resourced rural mothers with young children
      near Vadodara. Materials and Methods: Mothers of children <5 years (n = 160) were
      enrolled from four rural clusters near Vadodara based on their current growth
      status (weight-for-age) and were categorized as PD (n = 65) and negative deviant
      (ND; n = 95), as per the WHO Anthro Software. Personal interviews were conducted
      through household (HH) visits using a semistructured questionnaire. Data were
      elicited on HH socioeconomic status, infant and young child feeding practices,
      diet pattern, and hygiene-sanitation practices. HH dietary diversity score was
      calculated individually after collecting data through food frequency
      questionnaire. Results: Mothers had several significant PDBs (P < 0.05), PD group
      vs. ND group, less use prelacteals to children (53% vs. 71%) and had more
      exclusive breastfeeding rates (44% vs. 26%), provided cleaner clothing to
      children (52% vs. 28%), had sufficient intra-HH food distribution (30% vs. 18%),
      and scored better in dietary diversity at HH level (52% vs. 28%). Conclusions:
      PDBs and normal growth patterns do exist in poorly resourced areas, and these
      mothers can be used as "change agents" by the practicing pediatricians of rural
      communities for improving child health and nutrition.

PMID- 30294081
TI  - Association of Physical Problems and Depression with Elder Abuse in an Urban
      Community of North India.
AB  - Context: Elder abuse is a serious problem that has adverse consequence on health.
      Still, research on elder abuse is sparse in India. Aims: This study aimed to find
      the nature, prevalence, and factors such as depression and physical problems
      associated with elder abuse in an urban North Indian community. Materials and
      Methods: A cross-sectional study was conducted with 222 elders with 97 males,
      aged 60 years or older residing in an urban community of Delhi. Elders were
      assessed for abuse by modified Vulnerability to Abuse Screening Scale
      questionnaire, Geriatric Depression Scale, and self-reported questions on health
      problems. Results: Mean age of the study population was 66.3 +/- 4.2 years. The
      overall prevalence of any type of elder abuse was 24.3%. Psychological abuse was
      the most common type (22.9%) followed by financial abuse (5.8%), physical abuse
      (1.4%), and anti-constitutional abuse (nil). Among the abused, nearly 20%
      experienced more than one type of abuse. Thirty-seven women (30%) and 17 men
      (18%) reported elder abuse. Low income (<Rs. 10,000/month), female gender, and
      visual and hearing problems were risk factors for elder abuse while socially
      active and good health were protective against abuse. Depression and alcohol
      consumption were associated with elder abuse. Conclusion: Elder abuse is common
      in urban North India and is underreported. Appropriate interventions are required
      to ameliorate the problem.

PMID- 30294082
TI  - Ambiguity about Selection of Cardiovascular Risk Stratification Tools: Evidence
      from a North Indian Rural Population.
AB  - Background: Several nonlaboratory based cardiovascular disease (CVD) risk scoring
      tools are available for resource-limited settings, but the performance of these
      tools remains to be established in Indian population. This study aimed to assess
      and compare the performance of the World Health Organization (WHO)/International
      Society for Hypertension (ISH) risk prediction chart and the Framingham Risk
      Score (FRS) calculator in an Indian setting. Materials and Methods: This cross
      sectional study was carried out among 283 participants aged 30-74 years who
      attended screening camps in the rural area of Punjab from October to December
      2015. Nonlaboratory-based WHO/ISH risk prediction chart for South-East Asia
      Region and FRS calculator was used to assess the 10-year risk of cardiovascular
      event. Chi-square test for trend and quadratic weighted kappa were used for
      analysis. Results: Of total participants, 67.1% were female. Mean age of the
      study participants was 52.1 (standard deviation +/- 11.6) years. Using the
      WHO/ISH risk prediction chart, 11.3% and 4.9% of the participants were found to
      have high and very high risk, respectively, whereas, FRS calculator predicted
      high risk in 13.8% and very high risk in 12.0% for developing CVD in next 10
      years. Agreement level between two risk prediction tools was good (67.8%).
      Conclusion: Although the good agreement was seen between WHO/ISH risk prediction
      chart and FRS calculator, the proportions of participants having a high and very
      high risk of CVD identified by these risk prediction tools are significantly
      different. In resource constraint setting like India, CVD risk prediction tools
      should be validated for local population by prospective cohort studies to ensure
      judicious use of resources.

PMID- 30294083
TI  - Knowledge and Skills of Ayurvedic and Homeopathic Practitioners to Provide
      Skilled Birth Attendance in India: An Observational Study.
AB  - Background: To overcome the dearth of trained skilled birth attendants,
      mainstreaming of doctors from the alternative systems of medicine has been
      adopted by some states in India. Objectives: The objectives of the study were to
      explore the adequacy of knowledge and clinical skills of AYUSH practitioners
      (APs) (ayurvedic and homeopathic) engaged by the state governments to provide
      maternity care services, with a view to identify gaps if any, and to suggest
      measures for improvement. Materials and Methods: A cross-sectional observational
      study was conducted in three states of India (Maharashtra, Rajasthan, and
      Odisha). The APs were assessed for (a) knowledge of essential obstetric care and
      identification and management of complications of pregnancy and (b) clinical
      skills during provision of antenatal and postnatal care (PNC) and during the
      conduct of deliveries. Adequate knowledge or skill demonstration was defined as a
      score of 70% or more. Results: A total of 109 APs engaged in 37 peripheral level
      facilities were assessed. Nearly 76% of APs had adequate theoretical knowledge of
      essential obstetric care and identification and management of complications of
      pregnancy. Most APs demonstrated adequate skills while providing antenatal care
      but were deficient in taking past history and counseling pregnant women for
      danger signs during pregnancy and childbirth. APs in Maharashtra and Rajasthan
      had adequate skills for conducting vaginal deliveries but performed poorly in
      Odisha. Skills for resuscitation of newborn were deficient. Skills for providing
      PNC were adequate only among APs in Maharashtra. Conclusion: Through provision of
      appropriate in-service training and an enabling environment, APs may be a useful
      human resource for providing maternity care in the primary health-care settings
      in India.

PMID- 30294084
TI  - A Comparative Study on Social Media Usage and Health Status among Students
      Studying in Pre-University Colleges of Urban Bengaluru.
AB  - Introduction: Social Media usage is a "global consumer phenomenon" with an
      exponential rise within the past few years. The use of social media websites is
      among the common activity for today's adolescents, they are sometimes
      overused/misused, which may lead to social media addiction. Objectives: The
      objective of this study was to assess and compare the prevalence of social media
      addiction between Government and Private Pre-University (PU) college study
      subjects, to assess the health problems related to social media usage among the
      study subjects, and to assess the various factors associated with social media
      addiction. Materials and Methods: This cross-sectional study was conducted in
      Government and Private PU colleges situated in a selected ward of urban Bengaluru
      city through multistage sampling. A total of 1870 study subjects were recruited.
      A scale was developed to assess social media addiction. Results: The prevalence
      of social media addiction was 36.9% among users, distributed equally among
      private and Government PUs. The most common health problem identified was strain
      on eyes (38.4%), anger (25.5%), and sleep disturbance (26.1%). Being a male, the
      habit of smoking, alcohol, and tobacco, consumption of junk food, having
      ringxiety and selfitis were found to be significant risk factors for social media
      addiction. Conclusion: Social media addiction was found in over one-thirds of
      subjects and majority had mild addiction.

PMID- 30294085
TI  - Assessment of Tuberculosis Prevalence in Newly Diagnosed Human Immunodeficiency
      Virus-Infected Adults Attending Care and Treatment Center in Gujarat, India.
AB  - Background: Tuberculosis (TB) is first opportunistic infection and leading cause
      of death among human immunodeficiency virus (HIV)/AIDS. Certainly, the prevalence
      of TB is expected to differ between general population and HIV-infected persons.
      This study was conducted to determine the prevalence of TB among newly diagnosed
      HIV-infected adults attending antiretroviral therapy (ART) center in the state of
      Gujarat, India. Materials and Methods: Cross-sectional study was carried out
      among newly diagnosed HIV-infected persons attending ART center from July 2012 to
      September 2012. Screening of TB symptoms and chest X-ray was done for those who
      consented. Sputum samples were collected for microscopy with Ziehl-Neelsen method
      for all presumptive TB cases and those diagnosed as pulmonary TB, culture, and
      drug susceptibility test was done. Blood samples were collected for CD4+ T-cells
      count and hemoglobin. Results: Out of 2021 eligible HIV-infected persons, 63.5%
      were males and 68.2% were in the age group of 26-45 years. The prevalence of TB
      was 17.8%. Among 360 patients with TB, 102 (28%) had smear positive TB, 86 (24%)
      had smear-negative TB, and 172 (48%) were diagnosed as extrapulmonary TB. Two
      hundred and thirty-eight (27%) TB patients with CD4+ T-Cell count below 200
      compared to 122 (11%) patients above 200. Conclusion: A high prevalence of TB was
      found among newly diagnosed HIV-infected adults attending ART center for care and
      treatment. The prevalence of pulmonary and extrapulmonary TB was almost equal.
      Chances of TB disease were more with depletion of CD4 counts. The study
      highlights urgent need of intensive case finding as well as periodic screening of
      newly diagnosed HIV-infected individuals.

PMID- 30294086
TI  - Comparison between Weight-for-Height Z-Score and Mid Upper Arm Circumference to
      Diagnose Children with Acute Malnutrition in five Districts in India.
AB  - Background: The World Health Organization recommends weight-for-height Z-score
      (WHZ) or mid-upper arm circumference (MUAC) and bilateral pitting edema to
      diagnose acute malnutrition among children aged 6-59 months. WHZ and MUAC
      identify different sets of children with acute malnutrition, and overlap between
      their prevalence varies greatly among countries. Objective: The objective of the
      study was to determine the degree of overlap and agreement between WHZ and MUAC
      to diagnose children with acute malnutrition in India. Methods: Five nutrition
      surveys using Standardized Monitoring and Assessment of Relief and Transitions
      methodology were conducted in four Indian states. A total of 2127 children aged 6
      59 months were analyzed. All anthropometric indices were calculated using
      emergency nutrition assessment software and analyzed in Epi-Info 3.5.4. Results:
      Of total global acute malnutrition (GAM) cases, 96% and 28.4% cases were
      diagnosed with WHZ and MUAC, respectively. Similarly, of total severe acute
      malnutrition (SAM) cases, 95.1% were identified using WHZ and 30% using MUAC. The
      proportion of overlap between the two criteria for GAM and SAM cases was 24.5%
      and 25.2%, respectively. The analysis showed that MUAC was comparatively more
      sensitive to identify acute malnutrition among 6-23-month aged children and
      females. Conclusion: One-fourth of GAM and SAM cases were identified with both
      criteria. MUAC identified approximately 30% of the total SAM cases which was
      lower than other countries. MUAC identified more number of females and younger
      children, who may have higher mortality risk and would result significantly
      smaller caseload (68% smaller) that requires intervention compared to when using
      WHZ.

PMID- 30294087
TI  - Devadasi and Their Intimate Partners: Dynamics of Relationship.
AB  - Background: Devadasi practice is still prevalent in some parts of North
      Karnataka; most of the Devadasis get into sex work for their survival. During sex
      work, devadasis would get close to their customer, as they feel secure and
      emotionally satisfied. Objectives: The present study aims at understanding the
      Devadasi sex worker (DSW) and their intimate partners' (IPs) relationship and
      knowing the reasons for continuing the relationship even though they experience
      violence and abuse from their IP. Methods: Exploratory research design was
      adopted. Purposive sampling was used for the field visits. Data were gathered
      through personal interviews during field visits along with the counselors who
      were capacitated to deal with the relationship issues of DSWs and their IPs.
      Modified thematic analysis was used to analyze twenty field visit reports.
      Results: This study analyzed the quality and dynamics of the relationship between
      DSWs and their IP. DSWs and their IP define their relationship as "like marriage"
      without legal recognition. DSWs accept the violence from their IP as a symbol of
      love. Violence was identified as a key concern for the sex workers and is often
      acceptable in their relationship. Conclusion: The relationship between DSWs and
      their IPs needs to be understood before arriving at the care plan to deal with
      the relationship issues. There is an urgent need for developing an interventional
      model for the counselors and equip them to deal with the relationship issues of
      DSWs.

PMID- 30294088
TI  - Spatio-Temporal Risk-Analysis of Cancer Endemicity in Sulthan Bathery Taluk of
      Wayanad District of Kerala-A Geo-Informatics Approach.
AB  - Context: Asian countries have to confront with the global burden of cancer and
      various environmental factors predisposing the incidence. Geoinformatics can
      assist in spatial autocorrelation and statistical analysis in determining
      environmental and demographic correspondence to endemicity. What is of prime
      importance is the availability of the spatial datasets of cancer cases. Aims: The
      aim of this study was to reveal the distribution pattern of cancer and its
      magnitude in the eight panchayats of Sulthan Bathery Taluk of Wayanad district.
      The present study also attempted to develop and implement a data frame
      facilitating better data collection. Settings and Design: This was a taluk-level
      cross-sectional retrospective analysis and interventional study. Subjects and
      Methods: A retrospective survey created a geodatabase with 547 cancer cases
      registered along the timeline of 2015-2016. Input datasets were geocoded using
      Google Earth Pro software. Statistical Analysis Used: The analysis was performed
      using ArcMap-10.2 version. Results: Registration revealed the high breast cancer
      incidences and temporal increment mainly in town areas. The incidence depicted
      male predominance and prevalence along the age group of 30-69 years. The pattern
      showed cancer incidence at a proximity to state borders and forest regions
      (Noolpuzha) which are high population density regions, instantiated relation of
      geographic variables, and cancer incidences. The implementation of data frame
      ensured structured data collection. Conclusions: This study concluded the spatial
      association of cancer incidence demonstrating the high-risk regions with male
      predominance and role spatial risk analysis in cancer database management.

PMID- 30294089
TI  - Prediction Model of Tuberculosis Transmission Based on Its Risk Factors and
      Socioeconomic Position in Indonesia.
AB  - Context: The current evidence shows that people in low-socioeconomic positions
      tend to be at high risk for tuberculosis (TB) transmission. Aims: The aim of this
      study is to identify the significance of socioeconomic position and TB risk
      factors to TB transmission, particularly in Bandar Lampung, Indonesia. Settings
      and Design: This cross-sectional study, conducting in January-November 2017,
      included 166 samples of smear-positive TB patients collected from 30 community
      health centers across the city that had implemented DOTS strategy. Subjects and
      Methods: The latent variables consisted of the following: socioeconomic position,
      housing, nutritional, healthcare access, and TB transmission, which was measured
      through corresponding indicators. The data were collected through in-depth
      interviews. Statistical Analysis Used: Data analyzed using the partial least
      square method. Results: Determinants of socioeconomic position through housing
      determinants significantly influence TB transmission with R 2 of 42.3%. They also
      show that education, housing density index, and internal house transmission are
      the strongest indicators in explaining their associated latent variables.
      Conclusions: TB control program should be integrated with education improvement,
      a reduction of housing density index, and strengthened examinations of internal
      house contacts. These programs should be supported by health institutions and
      other related institutions. The findings will improve TB control programs,
      especially in low- and middle-income countries with high-socioeconomic disparity.

PMID- 30294090
TI  - District Level Analysis of Routine Immunization in Haryana State: Implications
      for Mission Indradhanush under Universal Immunization Programme.
AB  - Background: The immunization coverage in India is far away from satisfactory with
      full immunization coverage being only 62% at national level. Targeting the
      intensive efforts to poor performing areas and addressing the determinants of
      nonimmunization and dropouts offers a quick solution. In this paper, we assess
      the inter-district variations in Haryana state, and the association of social
      determinants with partial and no immunization. Methodology: This analysis is
      based on data collected as part of a large household survey undertaken in the
      state of Haryana to measure the extent of Universal Health Coverage. A multistage
      stratified random sampling design was used to select primary sampling units
      (i.e., subcenters), villages, and households. A total of 11,594 mothers with a
      child between 12 and 23 months were interviewed on receipt of immunization
      services. Determinants of nonimmunization and partial immunization were assessed
      using multiple logistic regression. Results: About 21% of children aged 12-23
      months were partially immunized, while 4.3% children aged 12-23 months had
      received "no immunization." While the coverage of full immunization was 74.7% at
      the state level, it varied from 95% in best performing district to 38% in poorest
      performing district. Odds of a partially immunized child were significantly
      higher in urban area (odds ratio [OR] = 1.23; 95% confidence interval [CI] = 1.1
      1.38), among Muslim household (OR = 3.52; 95% CI = 3.03-4.11), children of
      illiterate parents (OR = 1.58; 95% CI = 1.22-2.05), and poorest quintile (OR =
      1.61; 95% CI = 1.36-1.89). Conclusions: Wide interdistrict variations call for a
      need to consider changes in resource allocation and strengthening of the
      government initiatives to improve routine immunization in these districts.

PMID- 30294091
TI  - Analysis of Out-of-Pocket Expenditure in Utilization of Maternity Care Services
      in Urban Slums of Rajkot City, Gujarat.
AB  - Background: India contributes 20% global maternal deaths every year. An important
      reason of such maternal mortality is due to cost of maternity services which
      makes it in accessible to the poor. Knowledge of maternity-related expense and
      its determinants is useful for health authorities to focus public resources and
      target financial assistance or exemption guidelines toward the "neediest."
      Methodology: It was a cross-sectional descriptive study conducted amongst 180
      women living in urban slums and who had delivered a baby within 1 year of the
      interview date. Results: The mean cost of delivery was around Rs. 8880. The
      average delivery cost of private institutions was significantly higher than that
      of government hospitals or home delivery. Around 75% of women delivered in
      private institution had health expenditure of more than 10% of total annual
      family income - catastrophic expenditure. Conclusion: In spite of significantly
      higher maternity care-related costs in private institutes than government
      hospitals, majority of mothers had utilized services from private clinics and had
      suffered catastrophic expenditures during utilization of maternity care services.
      This study highlights the need for birth preparedness counseling as well as
      effective implementation of maternity benefit schemes to prevent families from
      pushing downward to the poverty line.

PMID- 30294092
TI  - Nicotine Dependence, Its Risk Indicators, and Exhaled Carbon Monoxide Levels
      among the Smokers in Bengaluru, India.
AB  - Background: Tobacco is the significant cause of preventable death worldwide. The
      prevalence of smoking in India is 13.3%. Among the chemical constituents in the
      cigarette, nicotine is the one most often associated with dependence resulting in
      increased consumption of them. Studies have proven the dose-dependent
      relationship of cigarette smoking with lung and oropharyngeal cancer. Hence,
      assessment of nicotine dependence among the smokers is essential as it influences
      the tailor-made intervention. Objectives: The objectives of this study were to
      assess the nicotine dependence and exhaled carbon monoxide (CO) levels among the
      smokers in Bengaluru. Materials and Methods: A cross-sectional survey was
      conducted among 396 smokers selected using probability proportional to size
      sampling technique. Fagerstrom Test for Nicotine Dependence was used to assess
      the levels of nicotine dependence. Exhaled CO levels were measured using the
      Smokerlyzer to indicate the nicotine dependence. Results: About 23.7% of the
      participants had the very low dependence on nicotine. Nearly 26% and 22.5% of the
      participants had the high and very high dependence on nicotine correspondingly.
      The number of years of smoking was found as a significant risk indicator for
      nicotine dependence. Exhaled CO levels were significantly correlated with the
      nicotine dependence (P = 0.000) indicating it as a marker for nicotine
      dependence. Conclusion: The high nicotine dependence among the participants
      warrants effective public health policies to prevent tobacco-related diseases.
      Considering the risk indicator, the number of years of smoking, smoking cessation
      programs should target the participants with the habit of continuous smoking with
      tailor-made interventions to prevent the relapse among them.

PMID- 30294093
TI  - Quality of Free Delivery Care among Poor Mothers in Gujarat, India: A Community
      Based Study.
AB  - Background: Government of Gujarat introduced a public-private partnership scheme
      called the Chiranjeevi Yojana (CY) in 2005, to improve access to delivery care
      for poor women. Till date, more than 1 million deliveries have been conducted
      under CY. Although CY has been evaluated, this is the only study using primary
      data to evaluate the quality of care. Objective: The objective of this study was
      to (i) determine the quality of free delivery care and (ii) examine the
      differences in the quality of care between public sector facilities and
      accredited private sector facilities. Methodology: The community-based survey was
      conducted in three districts of Indian state of Gujarat. Trained data collectors
      used pretested questionnaire in vernacular language between 7th and 10th days of
      delivery. Overall surveyed mothers were 3858 in the prospective study; analytic
      sample was 1616 mothers. Statistical analysis includes Chi-square test using IBM
      SPSS version 20. Results: Quality of care was perceived to be good in both public
      sector and accredited private sector. When free delivery care was compared
      between two sectors, private sector was perceived to have better quality of care.
      This difference was statistically significant for indicators, such as
      infrastructure, allowed to eat/change positions, application of pressure on
      abdomen, and weighing of baby. Conclusion: The study highlights the need for
      engaging private sector to improve access to delivery care for poor women.
      Quality assurance programs in Gujarat need to address respectful care issues in
      the public sector. Future research should include qualitative study to understand
      the drivers of quality delivery care.

PMID- 30294094
TI  - Morbidity Pattern and Role of Community Health Workers in Urban Slums of Durg and
      Bhilai City of Chhattisgarh.
AB  - Introduction: In 2002, the Government of Chhattisgarh initiated a Community
      Health Worker program called the Mitanin Program, to strengthen the health system
      of Chhattisgarh. The current study was conducted with the twin objectives to
      assess morbidity pattern and health-seeking behavior in urban slums of Durg and
      Bhilai to understand the role of Mitanins in health seeking of their slum
      population. Methods: Ten urban slums, five each from Durg and Bhilai were
      selected through simple random sampling for the study. Household survey was done
      using prestructured questionnaire. A total of 1025 households representing 4997
      family members were surveyed. Results: The study found that diseases which were
      most prevalent in the urban slums of Durg and Bhilai are blood pressure and
      diabetes mellitus. Diseases such as diarrhea, typhoid, hepatitis, tuberculosis,
      leprosy, and filariasis which have strong association with safe drinking water
      and sanitation are prevalent. For chronic communicable disease and reproductive
      and child health (RCH), people from both cities prefer going to public health
      care facilities. About a fourth of the population came in contact with the
      Mitanins to seek health care mostly in relation to chronic communicable diseases
      and RCH. Conclusion: The study shows an increase in the prevalence of chronic
      lifestyle diseases among the slum population. There is a case for inclusion of
      chronic conditions, as specified under Comprehensive Primary Health Care. There
      is a need to reprioritize Mitanin's role in early diagnosis through point-of-care
      diagnostics and ensuring prompt referrals and follow-up.

PMID- 30294095
TI  - Journey to Death: Are Health Systems Failing Mothers?
AB  - Background: Annually, about 44,000 maternal deaths occur in India, which is 20%
      of the global burden. Despite persistent efforts, India failed to meet the fifth
      millennium development goal by 2015. Lack of reliable data on maternal mortality
      demands utilization of tools for counting maternal deaths which is vital to
      implement preventative actions. Objectives: Our study aims to determine health
      system-related issues of maternal mortality using the WHO validated tool -
      Maternal Death Review and demonstrates usefulness of maternal death surveillance
      and review as a monitoring tool. Methods: Fourteen maternal deaths were evaluated
      through community based and facility-based audits from July 2013 to June 2014 in
      three districts of Gujarat. Pathways to death were traced through Global
      Positioning System (GPS). Factors contributing to the three delays were analyzed.
      Results: Type III delay, that is, delay in receiving adequate care was frequently
      observed in our review including weak referral linkages, lack of blood banking
      services, inadequate surgical facilities. and staff shortages. Mothers succumbed,
      not because they did not seek treatment or reach facilities in time but because
      facilities were incapable of providing appropriate medical care. Conclusion:
      Scaling up of maternal death audits and subsequent use of these findings will
      help to reduce maternal mortality in India. As we continue to push for
      institutional deliveries, we need to reevaluate if our health system is prepared
      to manage an increasing number of facility births and obstetric complications.

PMID- 30294096
TI  - Sexual and Reproductive Health Concerns of Adolescents Living with Perinatally
      Infected HIV in India.
AB  - Background: With improved access to highly active antiretrieval treatment, many
      children with perintally acquired HIV are now able live longer. These children
      are now reaching into adolescence and sexually active. This qualitative,
      explorative study examines the sexual and reproductive health (SRH) needs and
      concerns of adolescents living with HIV (ALHIV) in India. Materials and Methods:
      We used qualitative research design to collect the data. Twenty participants were
      recruited from two nongovernmental organizations which provide shelter care,
      education, and emotional and social support to HIV/AIDS orphan children located
      in Bengaluru District of Karnataka State using purposive sampling. In-depth
      interview guide was prepared and used to elicit the adolescents' concerns,
      knowledge, and perspective related to sexuality, marriage, child bearing, and
      barriers in availing SRH services in the context of HIV. Results: Totally, four
      themes were emerged from that qualitative data based on thematic analysis, which
      are as follows: "Perceived challenges in relation to romantic relationship;"
      "Confusion regarding whether to marry person with HIV positive or HIV negative;"
      "Aspiration to have children," and "Perspective of ALHIV in relation to SRH needs
      and concerns." Conclusion: The findings of the research brought out the need for
      policies and guidelines specifically targeting the SRH needs and concerns of
      ALHIV.

PMID- 30294097
TI  - Maternal Mortality Audit in Delhi: Further Perspectives.

PMID- 30294098
TI  - Response from the Authors (Singla et al)[1].

PMID- 30294099
TI  - Effect of Counseling on Newly Diagnosed Type 2 Diabetes Mellitus Patients
      Visiting a Tertiary Care Hospital: A Randomized Control Trial.

PMID- 30294100
TI  - Open Defecation-Free India by 2019: How Villages are Progressing?

PMID- 30294101
TI  - Health-Care Services Utilization Among Diabetes Patients Enrolled in Tertiary
      Care Hospital of East Delhi.

PMID- 30294102
TI  - Heartiset greetings from the editorial team.

PMID- 30294103
TI  - Apexification: A systematic review.
AB  - Pulpal necrosis in permanent teeth that have not completed their root development
      leads to teeth with a very short root, roots with very thin walls, and an
      inadequate crown-root ratio, which overshadows their survival prognosis.
      Currently, there are various therapies to treat immature permanent teeth with
      pulpal pathology such as the case of apexification. An electronic search was
      performed in the PubMed database (www.ncbi.nlm.nih.gov), Scopus (www.scopus.com),
      Cochrane (www.cochrane.org) to identify the clinical investigations related to
      evolution of the cases. The search of the literature of clinical studies on
      permanent teeth with open apex that present pulpar pathology and that need
      treatment, have been found 11 clinical studies of treatments with apexification.
      The apexification by calcium hydroxide has been applied for many years back to
      the present as a valid therapy to perform the treatment of apexification.

PMID- 30294104
TI  - Biodentine versus mineral trioxide aggregate as a direct pulp capping material
      for human mature permanent teeth - A systematic review.
AB  - Background: Biodentine is comparatively a new biomaterial claimed to have
      properties comparable to mineral trioxide aggregate (MTA). Biodentine and MTA are
      effectively used for direct pulp capping (DPC), and they are capable of
      regenerating relatively damaged pulp and formation of hard dentine bridge.
      Objectives: The aim of this systematic review was to test the null hypothesis of
      no difference between Biodentine and MTA as DPC materials for human permanent
      mature teeth, against the alternative hypothesis of a difference. Data Sources:
      Clinical trials were identified by electronic databases searches of Midline,
      CENTRAL Cochrane Library, Latin American and Caribbean Health Sciences
      Literature, Scopus, Scientific Electronic Library Online, evidence-based
      endodontics literature, KoreaMed, and Google Scholar. The literature search was
      performed from January 2010 to February 2018. Hand searches were also performed
      for relevant abstracts, books, and reference lists. Titles and abstracts of
      studies identified using the above-described protocol were independently screened
      by two authors. Full texts of studies judged by title and abstracts to be
      relevant were independently evaluated by two authors for stated eligibility
      criteria. Study Eligibility Criteria: The eligibility criteria included
      randomized clinical trials (RCTs) and non-RCTs. Participants: Patients with
      permanent mature molars indicated for surgical extraction or molars that have
      symptomless exposure of vital pulp tissue by caries or trauma. In both cases, the
      molars were subjected to DPC. Interventions: The pulp exposures were directly
      treated by Biodentine or MTA. Study Appraisal: To assess article quality, two
      authors independently used the risk of bias in nonrandomized studies - of
      interventions. Methods: Qualitative metasynthesis was used to analyze data across
      qualitative studies. Results: The initial search identified 8725 unique
      references through the search process. No additional studies were identified
      through handsearching. After filtering, 915 references were recorded and
      screened. After the eligibility criteria were applied, seven unduplicated
      prospective and retrospective cohort studies were included in the qualitative
      metasynthesis. Limitations: Further RCTs with much larger sample size and proper
      methodology with longer observational time are still in need to adequately
      address the questions of the present systematic review. Conclusion and
      Implications of Key Findings: Within the limitations of this review, it may be
      concluded that Biodentine had a similar effect on dentin bridge formation likely
      to MTA. However, this conclusion is based on only very few well-conducted
      prospective and retrospective cohort studies. Systematic Review Registration
      Number: The review had been registered with PROSPERO (registration number
      CRD42018089302).

PMID- 30294105
TI  - The influence of ProTaper and WaveOne on apically extruded debris: A systematic
      review and meta-analysis.
AB  - Background: Apically extruded debris produced during root canal preparation can
      induce postoperative inflammation and subsequent failure of root canal treatment.
      Therefore, debris production must be reduced to improve the outcome of root canal
      treatment. Aim: This study aimed to provide a theoretical basis for the
      improvement of root canal treatment by comparing the difference in the amount of
      apically extruded debris produced during the root canal preparation of extracted
      human teeth with ProTaper Universal (PTU), ProTaper Next (PTN), and WaveOne (WO).
      Materials and Methods: On March 30, 2017, three researchers searched five
      electronic databases (PubMed/Medline, Cochrane, Science Direct Online, Embase,
      and Web of Science) with no time limitations. Only articles written in English
      were retrieved, and 150 articles were obtained. Then, the three researchers
      independently selected articles in accordance with previously established
      inclusion and exclusion criteria, and inconsistent results were discussed. Data
      were analyzed through meta-analysis for standardized mean difference (SMD).
      Results: Eight studies met the inclusion criteria and were subjected to
      qualitative analysis. Four articles showed that PTU produced higher amounts of
      apical debris than WO; two articles showed that PTU produced lower amounts of
      apical debris than WO; and three articles showed that PTN produced lower amounts
      of apical debris than WO. Moreover, one article demonstrated that PTU produced
      higher amounts of apical debris than PTN. A meta-analysis showed that PTU and WO
      did not produce significantly different amounts of apically extruded debris: SMD
      = -0.26, Z = 0.50 (P > 0.05). PTU produced lower amounts of apically extruded
      debris than WO: SMD = -4.98, Z = 2.79 (P < 0.05). However, results were
      significantly heterogeneous among all the included studies (I 2= 97%). No
      significant difference was found between PTU and WO in the amounts of apically
      extruded debris: SMD = 0.47, Z = 1.06 (P > 0.05). Conclusion: Currently available
      evidence shows that PTN can produce lower amounts of apical debris than WO (P <
      0.05). Moreover, the amounts of apically extruded debris produced by PTU and WO
      are not significantly different (P > 0.05). Nevertheless, given the limited
      number of studies reviewed, a definitive conclusion cannot be reached.

PMID- 30294106
TI  - The internal anatomy of danger zone of mandibular molars: A cone-beam computed
      tomography study.
AB  - Aim: The aim of this study was the assessment of the anatomical thickness of
      danger zone in the cervical third of mesial canals of mandibular molars.
      Materials and Methods: Fifty mandibular molars were selected and scanned with
      cone-beam computed tomography. Data were compared using a length tool provided by
      scanner software. The measured areas were the mesial and distal walls of the
      cervical third of the mesial roots, which correspond to the safety and danger
      zones, respectively. In addition, dentin thickness at the furcation was
      evaluated. Results: Dentin thicknesses of the safety zone were higher than in the
      danger zone in all teeth examined. The thinnest dentin of the safety zone was
      found at a point located 4 mm below the canal orifice, with a mean value of 1.03
      mm; conversely, in the danger zone, the thinnest point was located 3 mm below the
      orifice, with a mean value of 0.81 mm. As for the distance from the pulp chamber
      floor to the furcation, the average value was 2.23 mm. Conclusion: These results
      show that mean thicknesses at the danger zone of mandibular molar mesial roots
      were <1.0 mm. These data reinforce the importance of understanding anatomy and
      the need for conservative preparations when assessing and instrumenting these
      root canals.

PMID- 30294107
TI  - Clinical evaluation of self-adhering flowable composite versus conventional
      flowable composite in conservative Class I cavities: Randomized controlled trial.
AB  - Background: Self-adhering flowable composite (SAFC) minimized the time-consuming
      application procedures encountered with the traditional adhesive systems and
      restorative materials. Self-adhering composite combines the merits of both
      adhesive and restorative material technologies (8th generation) in a single
      product, bringing new horizons, and ambitions to restorative procedures. Aim: The
      aim of this study was to evaluate the clinical performance of SAFC compared to
      conventional flowable composite in conservative Class I cavities. Materials and
      Methods: In a split-mouth design, after cavity preparation, 18 patients with
      conservative Class I cavities received randomly two pairs of restorations, either
      VertiseTM flow or FiltekTM Z350 XT Flowable combined with ScotchbondTM Universal
      Etchant and Single Bond Universal, all materials were applied according to the
      manufacturer's instructions. Restorations were evaluated at baseline and after 6
      months by two calibrated assessors using the modified United States Public Health
      Service criteria measuring (retention, postoperative hypersensitivity, color
      match, marginal adaptation, and marginal discoloration). Statistical Analysis:
      Chi-square test was used to compare between flowable composite materials after
      different follow-up periods, Wilcoxon signed-rank test was used to explore
      changes over follow-up periods. A value of P <= 0.05 was considered statistically
      significant. Results: At baseline and 6 months, there was no statistically
      significant difference between both materials for all tested outcomes.
      Conclusions: SAFC has shown clinical performance similar to conventional flowable
      composite after 6 months of clinical service.

PMID- 30294108
TI  - Porosity analysis of mineral trioxide aggregate Fillapex and BioRoot cements for
      use in endodontics using microcomputed tomography.
AB  - Aim: The purpose of this study is to compare the porosity of two sealant cements,
      mineral trioxide aggregate (MTA) Fillapex(r) and BioRoot(r) root canal sealer
      (RCS). These samples were analyzed using microcomputed tomography. Materials and
      Methods: Sixteen samples were used in the study that were divided according to
      the composition of the materials used. MTA Fillapex(r) (n = 8) and BioRoot(r) RCS
      (n = 8) were the samples prepared according to the manufacturer's instructions.
      They were placed in silicone molds of 5 +/- 0.1 mm in height and an internal
      diameter of 5 +/- 0.1 mm; 24 h after its preparation, the samples were scanned
      through a microcomputed tomography, and the porosity results were analyzed
      statistically by independent t-tests. Results: It is evident that MTA Fillapex(r)
      has better porosity properties than BioRoot(r) RCS. The results of the study
      quantify a smaller number of pores per surface, a smaller volume in each pore per
      mm3, and a lower total porosity present in samples of MTA Fillapex(r) unlike
      BioRoot(r) RCS samples which is larger in both. Conclusions: The results obtained
      in computerized microtomography endodontic biomaterial samples concluded that MTA
      Fillapex(r) has a lower porosity than BioRoot(r) RCS.

PMID- 30294109
TI  - Comparative evaluation of a low-level laser and topical desensitizing agent for
      treating dentinal hypersensitivity: A randomized controlled trial.
AB  - Aim: The aim of this randomized, controlled, double-blinded, clinical study is to
      evaluate and compare the clinical effectiveness of low-level diode GaAlAs laser
      and glutaraldehyde-based topical desensitizing agent on cervical dentin
      hypersensitivity with the help of visual analog scale (VAS). Materials and
      Methods: Fifty teeth of patients aged between 20 and 50 years were included, and
      VAS was used to assess the dentin hypersensitivity. The teeth were randomly
      allocated to either Group 1 or 2 using flip coin technique. Group 1 received
      glutaraldehyde desensitizer and Group 2 received 905 nm low-level laser. The
      sensitivity scores were recorded, immediately, after1 week and 3 months after
      therapy. Data was analyzed using Mann-Whitney U test for intergroup comparison
      and Friedman's test for intragroup comparison. Results: There was a significant
      reduction in pain in both the groups at 3 months evaluation (P = 0.001).However,
      Group 2 showed a significant decrease in mean VAS scores when compared with Group
      1 at both the one week and three month follow ups (P = 0.04, P = 0.03,
      respectively). Conclusion: Although topical desensitizer and Low Level Laser are
      both effective in reducing dentinal hypersensitivity, Low Level Lasers are
      comparatively more effective at the studied time intervals.

PMID- 30294110
TI  - Effect of different concentrations of carbamide peroxide on the staining
      susceptibility of resin composites.
AB  - Context: Bleaching can affect the surface properties of resin composites. Aims:
      The aim of this study was to evaluate the effect of three regimens of carbamide
      peroxide (CP) on staining susceptibility of silorane and methacrylate-based resin
      composites. Methods: In this study, 80 composite disks were prepared from A2
      shade of P90 and Z250 composite resins (40 each). Samples were divided into three
      test groups based on the CP concentration (10%, 16%, and 22%) and bleached for 14
      days. Controls were kept in distilled water. Then, specimens were immersed in a
      tea solution for 14 consecutive days. A spectrophotometer was used to measure the
      specimen colors in CIE L*a*b system, initially and after staining. Data were
      analyzed using SPSS 16 software using two-way ANOVA, t-test, and Tukey honestly
      significant difference tests at alpha = 0.05. Results: The color susceptibility
      of Z250 samples were significantly affected in groups bleached with 22% CP
      compared to the controls (P = 0.001). The different concentrations of CP did not
      affect the staining susceptibility of the P90 samples (P > 0.05). Conclusions:
      Bleaching of the tested resin composites did not increase their susceptibility to
      extrinsic staining in vitro except for the Z250 samples bleached with 22% CP.

PMID- 30294111
TI  - Stress distribution in a tooth treated through minimally invasive access compared
      to one treated through traditional access: A finite element analysis study.
AB  - Introduction: The purpose of this study was to compare the stress distributions
      in the teeth treated through minimally invasive access (MIA) designs to those of
      the teeth treated through traditional straight-line access and their relationship
      to the final restoration using three-dimensional finite element analysis (FEA).
      Materials and Methods: Four FEA models of an extracted mandibular first molar
      were constructed. An intact model served as the control, whereas the other three
      were prepared with either an MIA or traditional straight-line access. Simulated
      composite access fillings with or without a simulated gold crown were applied to
      the models, followed by application of an occlusal load of 100 N. Von Mises
      stresses in the teeth were then calculated and analyzed. Results: Stress values
      within the dentin for baseline, MIA with composite filling, MIA with composite
      filling and crown, and traditional access with composite filling and crown were
      10.14 MPa, 6.98 MPa, 11.79 MPa, and 16.81 MPa, respectively. Higher stress values
      indicate that the tooth is more prone to fracture. Conclusions: A traditional
      endodontic access cavity may render a tooth more susceptible to fracture compared
      with an MIA design.

PMID- 30294112
TI  - Clinical performance of resin-modified glass ionomer cement, flowable composite,
      and polyacid-modified resin composite in noncarious cervical lesions: One-year
      follow-up.
AB  - Background: The restoration of noncarious cervical lesions (NCCLs) often poses a
      challenge to the clinician. Various restorative materials are available in the
      market for the restoration of the same. Each material has various advantages and
      shortcomings. Aim: The aim of this study was to compare and to evaluate the
      clinical performance of capsulated resin-modified glass ionomer cement (RMGIC),
      flowable composite, and polyacid-modified composite resin (PMCR) in NCCLs.
      Materials and Methods: A total of 101 restorations were placed among healthy
      controls in this clinical trial. A total of 101 restorations were divided into
      three groups with n = minimum 32 per group (Group 1: 33 restorations, Group 2: 34
      restorations, and Group 3: 34 restorations). The restorative materials used were
      capsulated RMGIC, flowable composite and PMCR. After the placement, the
      restorations were evaluated for the United States Public Health Services criteria
      for six parameters, namely retention, marginal adaptation, marginal
      discoloration, color stability, surface roughness, and sensitivity. The
      restorations were evaluated at baseline, 6 and 12 months. Statistical Analysis:
      Statistics was performed using SPSS 21.0 version. Chi-square test was done to
      compare the proportions between groups. Fisher's exact test was used to compare
      proportion change between time points. Results: There was no statistically
      significant difference seen among the three groups for retention, color
      stability, surface roughness, and hypersensitivity. RMGIC had shown superior
      characteristics in marginal adaptation and marginal discoloration compared to
      flowable composite and PMCR, and the difference was statistically significant.
      Conclusion: Within the limitations of this study, all the three restorative
      materials are clinically acceptable for the restoration of NCCLs. RMGIC is
      superior regarding marginal adaptation and esthetics for restoring NCCLs.

PMID- 30294113
TI  - Comparative evaluation of grape seed and cranberry extracts in preventing enamel
      erosion: An optical emission spectrometric analysis.
AB  - Introduction: Dental erosion is defined as the loss of tooth structure due to
      chemical process that does not involve bacteria. The management of such a
      condition calls for a comprehensive approach to identifying the cause and
      treating it. Aim: The aim of this study is to comparatively evaluate the role of
      grape seed extract (GSE) and cranberry extract (CE) in preventing dental erosion
      using optical emission spectrometry. Materials and Methods: Prepared enamel
      specimens were subjected to the erosive challenge using HCl for 10 s, followed by
      immersion in experimental natural groups and control fluoride group for 30 s and
      artificial saliva for 60 min. This cycle was repeated three times. The amounts of
      calcium and phosphorous present in the acid solution after 1st, 2nd, and 3rd
      erosive challenges were determined for each group using induced coupled plasma
      optical emission spectrometry. Results: The cumulative calcium and phosphorous
      release after the 1st, 2nd, and 3rd erosive challenges were found to be the least
      in SnF2 group, followed by GSE group and then in CE group. Conclusion: The
      protective of GSE and CE was inferior to the gold standard control group of
      stannous fluoride role, against enamel erosion. GSE showed better remineralizing
      effect; however, there was no statistically significant difference between the
      two groups.

PMID- 30294114
TI  - Effect of root canal preparation, obturation, and retreatment on the induction of
      dentinal microcracks: A microcomputed tomography study.
AB  - Introduction: This study evaluated the effect of root canal preparation,
      obturation, and different techniques of retreatment on the percentage increase in
      the number of dentinal microcracks using microcomputed tomography (CT) analysis.
      Materials and Methods: Forty-five mandibular premolars after micro-CT scanning
      were prepared using Protaper universal files up to F4 and obturated. After the
      second micro-CT scanning again, the samples were randomly divided into three
      groups (n = 15) for retreatment procedure. In Group 1, retreatment was done with
      Protaper universal D1, D2, and D3 retreatment files followed by Protaper
      universal file till F4. In Group 2, retreatment was performed with R-Endo
      reciprocating motion, Re, R1, R2, R3, and Rs followed by Hero Shaper size #40. In
      Group 3, retreatment was performed with H-files and xylene till size #40. After
      gutta percha removal, the samples were again scanned for micro-CT for the
      evaluation of percentage increase in dentinal microcracks. Data were analyzed
      using "Kruskal-Wallis test ANOVA" and "student t-test" at 5% level of
      significance. Results: Few unprepared samples showed preexisting microcracks.
      There were statistically significant percentage increase dentinal cracks after
      root canal preparation and obturation as well as after retreatment procedure with
      statistically significant percentage increase in the number of dentinal
      microcracks between all three groups. Conclusion: Intraradicular procedures such
      as shaping and cleaning and obturation as well as the use of retreatment file
      lead to the induction and propagation of dentinal microcracks. In the present
      study, the maximum microcracks were produced with Protaper universal retreatment
      file system followed by R-Endo system. H-files produced minimum cracks during
      retreatment procedures.

PMID- 30294115
TI  - Cone-beam computed tomographic analysis of middle mesial canals and isthmus in
      mesial roots of mandibular first molars-prevalence and related factors.
AB  - Context: The internal anatomy of mandibular first molars has been studied in
      depth in different populations. However, limited information is present in
      differentiating a true middle mesial (MM) canal from an isthmus. Aims: The
      primary aim of this study was to identify the prevalence of a true MM canal and
      isthmus by retrospectively analyzing cone-beam computed tomography (CBCT) images
      in vivo. The secondary aim was to determine any correlation between related
      factors such as sex and age. Materials and Methods: CBCT images of 130 patients
      with the age group of 13-70 years were selected. Findings of MM canals and
      isthmus were recorded along with variables such as age and sex. Prevalence was
      compared using the Chi-square test (P < 0.05). Results: Out of 143 mandibular
      first molars, the prevalence of the MM canal was 18.2%. There was no
      statistically significant difference between sex and prevalence of the MM canal
      and isthmus. The prevalence of isthmi in the mesial roots was 78.4%. Their
      presence was significantly higher in the apical third area (37.1%) (P < 0.05).
      Both MM canal and isthmus were seen significantly higher in the age group of 31
      50 years (P < 0.05). Conclusions: This study showed a high prevalence of MM
      canals (18.2%) and isthmus (78.4%). The prevalence of the MM canal and isthmi was
      significantly higher in the middle age groups. This knowledge may direct the
      clinicians in locating them leading to good endodontic prognosis.

PMID- 30294116
TI  - Spectrophotometric evaluation of white spot lesion treatment using novel resin
      infiltration material (ICON(r)).
AB  - Aims and Objectives: The aim of this study is to compare the esthetic improvement
      of white spot lesions (WSLs) treated by icon, sodium fluoride (NaF), and
      bioactive glass using VITA Easyshade(r) spectrophotometer. Methodology: Ninety
      intact human maxillary central incisors were collected and artificial WSLs were
      created on facial surface having dimensions of 4 mm * 4 mm by immersing in
      demineralized solution for 4 days, baseline comparisons were performed by
      measuring the color of the WSLs compared to the adjacent sound enamel. All
      samples were divided into three groups of 30 each. Three groups were Group 1:
      Treated by NaF, Group 2: Treated by the bioactive glass, and Group 3: ICON(r)-DMG
      America (Resin infiltration). After treatment, the specimens of all groups were
      stored in artificial saliva and reevaluated at 4 and 8 weeks after the beginning
      of the treatments with VITA Easyshade(r) spectrophotometer. Results: Statistical
      analysis was performed with One-way analysis of variance. Post hoc analysis with
      the Tukey's honest significant difference test was used to compare the data
      between the groups. Among three groups, resin infiltration has significant color
      change (DeltaE) of infiltrated lesions when compared to other treatment groups (P
      < 0.001). Conclusion: Within the limitations of this study, it can be concluded
      resin infiltration (ICON(r)) can improve the esthetic characteristics of WSLs.
      Resin (ICON(r)) is a better treatment option when compared to bioactive glass and
      NaF as concerned to esthetics.

PMID- 30294117
TI  - Comparative evaluation of remineralizing efficacy of biomimetic self-assembling
      peptide on artificially induced enamel lesions: An in vitro study.
AB  - Background: The biomimetic self-assembling peptide technology is a paradigm for
      dental hard tissue regeneration. Aim: To investigate the efficacy of biomimetic
      self-assembling peptide (P11-4) on enamel remineralization compared to casein
      phosphopeptide-amorphous calcium phosphate fluoride (CPP-ACPF) and fluoride-based
      delivery systems. Materials and Methods: Artificial enamel lesions were created
      on buccal surfaces of 40 extracted human molars. Specimens were randomly assigned
      to four groups (n = 10) according to the remineralizing agent used: G1 - control:
      artificial saliva, G2 - fluoride varnish, G3 - CPP-ACPF varnish, G4 - self
      assembling peptide agent. All products were applied according to the
      manufacturer's instructions and the specimens were stored in daily renewed
      artificial saliva. Surface microhardness (SMH) was assessed at baseline, after
      demineralization, after 1 week and after 4 weeks storage. SMH values were
      analyzed using ANOVA and Tukey's post hoc test. Results: Self-assembling peptide
      showed the highest statistically significant mean SMH followed by fluoride and
      CPP-ACPF while the lowest mean SMH was found in artificial saliva. However, no
      statistically significant difference was found between fluoride and CPP-ACPF.
      Higher statistically significant mean SMH was found after 4 weeks compared to 1
      week remineralization in all groups. Conclusions: Self-assembling peptide confers
      the highest remineralizing efficacy compared to fluoride and CPP-ACPF, showing a
      promising, noninvasive regeneration potential. Furthermore, extended period of
      time helped attain more benefits from the remineralizing regimens applied.

PMID- 30294118
TI  - Effect of alcoholic beverages on shear bond strength of composites to enamel.
AB  - Background: Longevity of composite restoration in the oral cavity is dependent on
      various factors. One such factor is exposure to various foods and beverages which
      could alter the properties of the material. Aim: The aim of this in vitro study
      was to evaluate the effect of most widely consumed alcoholic beverages on shear
      bond strength of composites to enamel. Material and Methods: A total of seventy
      human premolars were embedded in acrylic resin blocks. Labial enamel surfaces was
      flattened, etched, bonded, and restored with composite resin (Tetric N Ceram -
      Ivoclar Vivadent AG, Schaan, Liechtenstein). The specimens were randomly divided
      into four groups: Group I: beer; Group II: wine; Group III: whiskey, and Group
      IV: artificial saliva. Group I to Group III were again divided into moderate
      (Group IA, IIA, and IIIA) and heavy (Group IB, IIB, and IIIB) consumption
      subgroups. The specimens were soaked in their respective groups for 90 min daily
      in Group IA, IIA, and IIIA and for 30 min every alternate day in Group IB, IIB,
      and IIIB until 30 days. Universal testing machine was used to determine the shear
      bond strength of composite with enamel. Statistical Analysis Used: The values
      obtained were statistically analyzed using two-way analysis of variance followed
      by post hoc test with the significant level set at P < 0.05, using GraphPad prism
      software version 6.01. Results: Group IIB showed the highest reduction in shear
      bond strength, with a mean value of 6.6 +/- 1.2 Mpa in comparison to control with
      a mean value of 21.8 +/- 1.6 Mpa. Conclusion: As the content of alcohol and time
      of exposure increased along with a decrease in the pH of alcoholic beverages,
      shear bond strength between composite and enamel decreased.

PMID- 30294119
TI  - Assessment of pain and dissolution of apically extruded sealers and their effect
      on the periradicular tissues.
AB  - Aim: This study aimed to evaluate the intensity of pain after unintentional
      extrusion of resin-based and calcium hydroxide (Ca[OH]2)-based endodontic sealers
      as well as their influence on the periradicular tissues. Materials and Methods: A
      total of 120 single-rooted teeth exhibiting extrusion of sealer in the
      postoperative radiographs were included in the study. According to the sealers
      used, the teeth were divided into four groups (n = 30): Group I - AH Plus(r),
      Group II - Resino Seal, Group III - SealapexTM, and Group IV - Apexit(r) Plus.
      Postoperative pain was assessed at 0-6 h, 6-12 h, 12-24 h, and 24-48 h of
      obturation using Visual Analog Scale. Radiographs were taken at 3, 6, and >=9
      months to 1-year follow-up and compared with baseline radiographs to assess the
      dissolution of extruded sealers and healing of periradicular tissues. Statistical
      Analysis: ANOVA, Kruskal-Wallis, and Pearson's Chi-square test were used.
      Statistical significance level was set at P <= 0.05. Results: Postoperative pain
      intensity was higher in case of AH Plus(r) sealer followed by SealapexTM up to 12
      h of obturation and was statistically nonsignificant. Apexit(r) Plus at all time
      intervals showed statistically significant less pain intensity than AH Plus(r)
      and SealapexTM but not from Resino Seal group. At 9-month follow-up, better
      healing of periradicular tissues was shown by AH Plus(r) (48.1%) followed by
      Apexit(r) Plus (44.4%) and SealapexTM (41.2%) with statistically nonsignificant
      difference. Conclusion: In case of periapical extrusion, both resin-based and
      Ca(OH)2-based sealers caused postoperative pain. Both Ca(OH)2- and resin-based
      sealers did not influence the treatment outcome.

PMID- 30294120
TI  - Effect of ultrasonic activation on calcium ion quantification, smear layer
      removal, and canal cleaning efficacy of demineralizing irrigants.
AB  - Background: Effective removal of smear layer ensures better penetration of
      irrigants ensuring root canal disinfection and has the potential of sealing
      dentinal tubules during obturation. Aim: The aim of this study is to evaluate the
      canal cleaning efficacy and calcium ion liberation with the use of demineralizing
      irrigants, namely, 17% ethylenediaminetetraacetic acid (EDTA), 7% maleic acid,
      and 10% citric acid with or without ultrasonic (US) activation. Materials and
      Methods: Crowns of 62 extracted maxillary central incisors were decoronated and
      root canals prepared. Based on the final irrigant teeth were divided into
      following groups (n = 10), namely, 10% citric acid, 7% maleic acid, 17% EDTA, and
      10% citric acid with US activation, 7% maleic acid with US activation, and 17%
      EDTA with US activation. Irrigants were subjected to inductively coupled plasma
      atomic emission spectroscopy followed by debris scoring and scanning electron
      microscope analysis. Statistical Analysis: One-way analysis of variance with the
      Bonferroni's correction for multiple testing was employed. Results: About 10%
      citric acid with US activation liberated the highest calcium ions and removed the
      maximum smear layer. Conclusions: Citric acid with US activation is a potentially
      effective irrigation regimen with sodium hypochlorite.

PMID- 30294121
TI  - Stress distribution in endodontically treated abfracted mandibular premolar
      restored with different cements and crowns: A three-dimensional finite element
      analysis.
AB  - Context: Noncarious cervical lesions may penetrate the pulp and require root
      canal treatment followed by crown placement. Such teeth may be susceptible to
      fracture, especially at the cervical area. Aims: To estimate which combination of
      restorative material and crown resulted in homogenous stress-strain distribution
      of endodontically treated abfracted mandibular premolar using three-dimensional
      finite element model (FEM). Settings and Design: A three-dimensional model of
      mandibular single-rooted premolar along with alveolar bone was created in finite
      element analysis (FEA) software preprocessor ANSYS rel 14.5 FEM software (ANSYS
      Inc., Houston, USA, 1994). Cervical lesion was created in the model with specific
      dimensions, 3 mm mesiodistally and 2 mm gingivoocclusally with enamel occlusal
      margin and dentin gingival margin. Materials and Methods: Tooth was simulated to
      be root canal treated and restored with different types of cements and crowns
      followed by placing a static load of 300 N at an angle of 135 degrees . Analysis
      was run and stress distribution pattern was studied. Results: Cervical region of
      an endodontically treated tooth is subjected to stresses, irrespective of
      restorative material used. Porcelain fused to metal (PFM) crowns showed least
      strain values with different postendodontic, restorative materials. Conclusions:
      FEA is a predictable and reproducible model to predict stress-strain behavior.
      PFM crowns with different postendodontic restorative materials showed least
      strain values in the cervical area of abfracted, endodontically treated
      premolars.

PMID- 30294122
TI  - Prevention of coronal discoloration induced by root canal sealer remnants using
      Dentin Bonding agent: An in vitro study.
AB  - Introduction: Among the various causes of tooth discoloration after root canal
      treatment, percolation of sealer remnants into the dentinal tubules of the pulp
      chamber is the most common cause. Objectives: The aim of this study is to
      evaluate the efficacy of dentin bonding agent (DBA) in preventing coronal
      discoloration caused by four different root canal sealers- MTA Fillapex,
      Sealapex, Zical and Z. O. B seal at different time intervals by measuring
      chromatic alterations using digital images analysis method. Methodology: Ninety
      mandibular premolars were collected and sectioned at 1 mm below the cementoenamel
      junction. Standard access cavity preparations of dimensions (depth-3 mm, width
      0.8 mm, and length-3 mm) were prepared with a No. 245 bur through the cervical
      access. Following the standard irrigation protocol, specimens were then randomly
      divided into nine groups (four groups without DBA [1-4] +4 groups with DBA [5-8]
      +1 negative control [9]). In Groups 1-4, four different root canal sealers (MTA
      Fillapex, Sealapex, Zical, and Z.O.B seal) were applied to the walls of the pulp
      chamber. For Groups 5-8, the samples were etched with 37% phosphoric acid and DBA
      application was done before the respective root canal sealer application. The
      cervical access in all specimens was sealed using glass ionomer cement. Digital
      photographs were taken under standard lighting and environmental conditions at
      different time intervals: preprocedural, postprocedural, and after 1, 2, 3, and 4
      months. These images were analyzed using Adobe Photoshop CS6 from which
      laboratory values and subsequently Delta E values were obtained. Results:
      Statistical analysis performed using repeated measures ANOVA and post hoc Tukey's
      tests show that the groups with DBA application had significantly lower mean
      Delta E values (P < 0.05) compared to the groups without DBA application.
      Conclusion: DBAs applied to the dentinal walls of the pulp chamber before
      obturation can effectively reduce the sealer-induced coronal discoloration.

PMID- 30294123
TI  - Intracanal heating of sodium hypochlorite: Scanning electron microscope
      evaluation of root canal walls.
AB  - Introduction: The aim of this study is to evaluate the surface of root canals
      dentine using scanning electron microscope (SEM) after instrumentation with
      rotary Nickel-Titanium systems and two different protocols of activation of
      sodium hypochlorite (NaOCl) (extracanal heating at 50 degrees C and intracanal
      heating at 180 degrees C), to assess the presence/absence of smear layer and also
      the presence/absence of open dentinal tubules along the walls at the coronal,
      middle, and apical third of each sample. Materials and Methods: Thirty-six single
      rooted teeth were selected, divided into three groups and shaped with ProTaper
      Universal instruments following irrigation protocols with 5.25% NaOCl. At the end
      of the preparation, three different protocols of activation were used: nonheated
      NaOCl in Group A, extra-canal heated NaOCl at 50 degrees C for Group B and
      intracanal heated NaOCl at 180 degrees C for Group C. Specimens were cut
      longitudinally and analyzed by SEM at standard magnification of *1000. The
      presence/absence of the smear layer as well as the presence/absence of open
      tubules at the coronal, middle, and apical third of each canal were estimated
      using a five-step scale for scores. Numeric data were analyzed using Kruskal
      Wallis and Mann-Whitney U statistical tests and significance was predetermined at
      P < 0.05. Results: Kruskal-Wallis analysis of variance (ANOVA) for debris score
      showed significant differences among the Ni-Ti systems (P < 0.05). Mann-Whitney
      test confirmed that Group A presented significantly higher score values than
      other Ni-Ti systems. The same results were assessed considering the smear layer
      scores. ANOVA confirmed that the apical third of the canal maintained a higher
      quantity of debris and smear layer after preparation of all the samples.
      Discussion and Conclusions: Intra-canal heating of NaOCl at 180 degrees C proved
      to be more effective in obtaining clean canal walls. On the other hand, extra
      canal heating at 50 degrees C of NaOCl left a higher quantity of debris and the
      smear layer was widely represented.

PMID- 30294124
TI  - Endodontic management of double dens invaginatus in maxillary central incisor.
AB  - This case report deals with the successful endodontic treatment of double dens
      invaginatus in maxillary left central incisor. Dens invaginatus is a rare
      developmental anomaly that is challenging to diagnose and treat. A patient
      reported with unesthetic appearance and previously attempted endodontic treatment
      of tooth #21. Cone beam computed tomography revealed the presence of a complex
      invagination communicating with the periodontium. A combination of techniques
      enhanced the debridement of the complex invagination. Obturation was performed
      using warm vertical compaction. The patient was asymptomatic during the follow-up
      period of 12 months.

PMID- 30294125
TI  - Endodontic management of invasive cervical resorption: Report of two cases.
AB  - Invasive cervical resorption of the tooth is a relatively rare and uncommon
      phenomenon where the etiology remains idiopathic and unclear, and if not treated
      may lead to ultimate loss of tooth structure. Advancements in digital imaging
      have made the clinician to diagnose the pathological changes with great
      precision. Proper diagnosis and management of this condition is key to the
      successful outcome. The aim of this article was to elaborate two case reports of
      invasive cervical root resorption with surgical management using biocompatible
      restorative material.

PMID- 30294126
TI  - Deducing a surgical dilemma using a novel three dimensional printing technique.
AB  - Persistent apical periodontitis even after nonsurgical retreatment demands for a
      surgical approach. This requires a thorough diagnosis and planning to eliminate
      the pathology and induce healing. This is sometimes challenging when the
      pathology is present in close relationship to the vital structures. In such
      cases, modern, sophisticated technology such as three-dimensional (3D) printing
      can come very handy in patient education as well as for planning and mock-up
      preparation of the surgery. In this case, a nonhealing persistent apical
      periodontitis in relation to 16 was surgically treated. However, the pathology
      was in close association with the maxillary sinus hence fused deposition modeling
      based 3D printed models were fabricated for patient education and to locate and
      determine the extent of the lesion. This was followed by the surgical enucleation
      of the lesion and apicectomy of mesiobuccal and distobuccal roots and mineral
      trioxide aggregate retro-filling and as the symptoms subsided after the follow-up
      full coverage metal crown was fabricated and cemented. This technology has opened
      a new horizon for the use of 3D printing in conjugation with endodontic
      principles for more predictable endodontic success.

PMID- 30294127
TI  - The Importance of Serial Time Point Quantitative Assessment of Cardiac Troponin I
      in the Diagnosis of Acute Myocardial Damage.
AB  - Objective: The present study was aimed to establish a threshold value for cardiac
      troponin I (cTnI) for nonacute coronary syndrome (ACS) participants from the
      local population and also to determine the importance of serial time point
      estimation of cTnI in acute myocardial infarction (AMI), non-ST-elevated MI
      (NSTEMI), and unstable angina cases. Methods: The present study included 194
      cases, admitted in ICCU with the complaint of anginal pain; 31 were diagnosed
      with AMI with typical electrocardiography (ECG) changes; whereas, 48 cases were
      diagnosed with NSTEMI. The latter group of cases was selected for the time point
      study of cTnI release at 0-4 h, 6-12 h, 72 h, and 144 h of admission. cTnI levels
      were assessed using the Abbott ARCHITECT i1000SR system. Results: ACS was
      clinically ruled out in 98 cases, and cTnI level for them was used to decide cTnI
      threshold for the non-ACS group. cTnI level was checked in 17 cases of unstable
      angina. The threshold value of cTnI for non-ACS participants was 0.1 ng/ml and
      can be considered as cut-off value for the regional population. The data
      suggested that the peak of cTnI levels in most of the AMI cases reached during 6
      12 h. The cTnI levels were lower than 0.1 ng/ml, and no significant change in ECG
      was noticed in 17 cases of unstable angina. Conclusion: The present study
      suggested that the repeat of cTnI assay after 4-6 h of admission is required if
      the initial value is <3 ng/ml.

PMID- 30294128
TI  - Non- Neurological Complications after Traumatic Brain Injury: A Prospective
      Observational Study.
AB  - Introduction and Aims: Recognizing and treating nonneurological complications
      occurring in traumatic brain injury (TBI) patients during intensive care unit
      (ICU) stay are challenging. The aim is to estimate various nonneurological
      complications in TBI patients. The secondary aim is to see the effect of these
      complications on ICU stay, disability, and mortality. Materials and Methods: This
      was a prospective observational study at the neuro-ICU of a Level-I trauma
      center. A total of 154 TBI patients were enrolled. The period of the study was
      from admission to discharge from ICU or demise. Inclusion criteria were patients
      aged >16 years and patients with severe TBI (Glasgow coma score [GCS] <=8).
      Nonneurological complications were frequent in TBI patients. Results: We observed
      respiratory complications to be the most common (61%). Other complications, in
      the decreasing order, included dyselectrolytemia (46.1%), cardiovascular (34.4%),
      coagulopathy (33.1%), sepsis (26%), abdominal complications (17.5%), and acute
      kidney injury (AKI, 3.9%). The presence of systemic complications except AKI was
      found to be significantly associated with increased ICU stay. Most of the
      patients of AKI died early in ICU. Respiratory dysfunction was found to be
      independently associated with 3.05 times higher risk of worsening clinical
      condition (disability) (P < 0.018). The presence of cardiovascular complications
      during ICU stay (4.2 times, P < 0.005), AKI (24.7 times, P < 0.02), coagulopathy
      (3.13 times, P < 0.047), and GCS <6 (4.2 times, P < 0.006) of TBI was
      independently associated with significantly increased risk of ICU mortality.
      Conclusion: TBI patients tend to have poor outcome due to concomitant
      nonneurological complications. These have significant bearing on ICU stay,
      disability, and mortality.

PMID- 30294129
TI  - Targeted-Volume Noninvasive Ventilation Reduces Extubation Failure in
      Postextubated Medical Intensive Care Unit Patients: A Randomized Controlled
      Trial.
AB  - Purpose: Till date, the benefit of using noninvasive ventilation (NIV) routinely
      after extubation to prevent reintubation has been conflicting. We aim to
      demonstrate the effect of targeted-volume NIV for the prevention of reintubation
      and extubation failure after planned extubation in medical intensive care unit
      (ICU) patients. Study Design: This was a prospective, randomized controlled
      study. Materials and Methods: Patients on invasive mechanical ventilation for
      more than 48 hrs for acute respiratory failure, who were ready for extubation,
      were randomized into targeted-volume NIV (intervention group) or oxygen mask
      (controlled group) immediately after extubation and continuously for 24 hrs.
      Results: A total of 58 patients were enrolled in this study. The targeted-volume
      NIV group was observed to have a trend toward lower reintubation rate within 48
      hrs compared to oxygen mask group (0% vs. 17.2%; P = 0.052). Extubation failure
      rate within 48 hrs was significantly lower in targeted-volume NIV group compared
      to oxygen mask group (0% vs. 41.38%; P < 0.001). There was a trend toward lower
      ICU length of stay (6[5] days vs. 10[8] days (median interquartile range [IQR]);
      P = 0.053) as well as shorter hospital length of stay after extubation (10[19]
      days vs. 18[15] days (median [IQR]); P = 0.059). There were no differences in the
      incidence of ventilator-associated pneumonia (VAP)/hospital-acquired pneumonia
      (HAP) (6.90% vs. 20.69%;P = 0.253) and 28 day-mortality (13.79% vs. 20.69%; P =
      0.487). Conclusions: Our study is the first study to demonstrate the benefit of
      application of targeted-volume NIV immediately after extubation in reducing
      extubation failure rate. There was a trend toward lowering reintubation rate and
      shorter ICU length of stay and hospital length of stay after extubation in mixed
      medical ICU patients.

PMID- 30294130
TI  - Sonographic Measurement of Optic Nerve Sheath Diameter: How Steep is the Learning
      Curve for a Novice Operator?
AB  - Background: Transbulbar sonography for measuring optic nerve sheath diameter
      (ONSD) is noninvasive bedside technique for detection of raised intracranial
      pressure. This study aims to evaluate the number of sonographic evaluations
      required for a novice operator to learn proper measurement of ONSD after a formal
      training and supervised scanning session. Methods: Three novice operators and one
      expert operator measured ONSD of 27 healthy volunteers using linear array
      transducer HFL38x (frequency range of 6-13 MHz) (MicroMaxx(r); SonoSite, USA). In
      each eye, ONSD was measured three times by each observer and mean value was
      determined. Correlation coefficient was calculated between the novice and the
      experienced operator and in between the novice operators. Number of scans, after
      which the significant correlation developed between novice and the experienced
      operator and between the novice operators, was analyzed. Results: Cronbach's
      alpha was tested to evaluate the reliability of the values obtained from intra-
      and interobservations. For all 27 cases, the value of Cronbach's alpha was high:
      0.80-0.99 for the right eye and 0.69-0.97 for the left eye. The mean
      interobserver variations were plotted on a graph which fluctuated largely in the
      first 17 cases but oscillated around 0.5-0.30 in the last 10 cases. Conclusion:
      Learning curve for novice operators to measure ONSD is steep and they can be
      taught to measure ONSD in healthy volunteers by sonography in supervised clinical
      session with an acceptable clinical precision and accuracy comparable to an
      experienced operator.

PMID- 30294131
TI  - Evaluating Extravascular Lung Water in Sepsis: Three Lung-Ultrasound Techniques
      Compared against Transpulmonary Thermodilution.
AB  - Background: Excessive extravascular lung water (EVLW) is associated with
      increased morbidity and mortality. We compared three lung-ultrasound (L-US)
      techniques against the reference-standard transpulmonary thermodilution (TPTD)
      technique to access EVLW. Materials and Methods: This was a prospective, single
      blind, cross-sectional study. Forty-four septic patients were enrolled. EVLW
      index was measured by the TPTD method, and an index of >=10 mL/kg was considered
      diagnostic of pulmonary edema. EVLW index was then compared to three established
      bedside L-US protocols that evaluate sonographic B-lines: (1) a 28-zone protocol
      (total B-line score [TBS]) (2) a scanning 8-region examination, and (3) a 4-point
      examination. Results: Eighty-nine comparisons were obtained. A statistically
      significant positive correlation was found between L-US TBS and an EVLW index
      >=10 mL/kg (r = 0.668,P < 0.001). The 28-zone protocol score >=39 has a
      sensitivity of 81.6% and a specificity of 76.5% to define EVLW index >=10 mL/kg.
      In contrast, the positive 4-point examination and scanning 8-regions showed low
      sensitivity (23.7% and 50.0%, respectively) but high specificity (96.1% and
      88.2%, respectively). Ten patients with a total of 21 comparisons met criteria
      for acute respiratory distress syndrome (ARDS). In this subgroup, only the TBS
      had statistically significant positive correlation to EVLW (r = 0.488,P = 0.025).
      Conclusion: L-US is feasible in patients with severe sepsis. In addition, L-US 28
      zone protocol demonstrated high specificity and better sensitivity than
      abbreviated 4- and 8-zone protocols. In ARDS, the L-US 28-zone protocol was more
      accurate than the 4- and 8-zone protocols in predicting EVLW. Consideration of
      limitations of the latter protocols may prevent clinicians from reaching
      premature conclusions regarding the prediction of EVLW. Trial Registration:
      ISRCTN11419081. Registered 4 February 2015 retrospectively.

PMID- 30294132
TI  - Survey on Perceived Impact of Religion, Culture, and Social Network Information
      on Surrogate Decision-making in a South Asian Developed Country.
AB  - Introduction: Relatives often have to assume responsibility for making end of
      life choices as surrogate decision-makers for patients with diminished or are
      lacking capacity. Our aim was to study the influence of religion, culture and
      social network information on surrogate decision making. Methods: This study was
      an exploratory, prospective, survey. Questions addressed the role of surrogates
      in decision making and the importance and influence of religion, culture and
      social media on such decisions. Results: 34 respondents filled out the anonymous
      survey. Surrogate decision making is a complex process and influenced by many
      factors. Conclusion: This survey points to a need for wider studies looking at
      the factors influencing people when making such important decisions and further
      social psychology interventions to evaluate whether such decisions can be made
      more consistent and patient centred.

PMID- 30294133
TI  - Diagnostic and Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Early and
      Late Phase of Sepsis.
AB  - Objective: Early diagnosis of sepsis is necessary to decrease morbidity and
      mortality. This study aims to evaluate neutrophil-to-lymphocyte ratio (NLR) as
      diagnostic and prognostic of early and late phase of sepsis. Methods: It was a
      prospective, observational study, conducted in Intensive Care and High Dependency
      Unit (Daycare) of the Department of Pulmonary and Critical Care Medicine
      (tertiary care center), Rohtak, from January 2017 to December 2017. A total of 56
      cases of newly diagnosed cases of sepsis were included in the study and 20
      healthy adults were taken as controls. Daily NLR was calculated in cases till the
      primary outcome. Results: The results suggested that NLR seems to have promising
      role as diagnostic and prognostic marker (with P = 0.001 and P = 0.045,
      respectively) in sepsis. Conclusion: The study suggests that NLR can be a useful
      diagnostic and prognostic marker in sepsis.

PMID- 30294134
TI  - Hypernatremia due to Urea-Induced Osmotic Diuresis: Physiology at the Bedside.
AB  - Hypernatremia secondary to urea-induced solute diuresis is due to the renal
      excretion of electrolyte-free water. This concept is explained here step-wise
      physiologically with the help of a clinical vignette.

PMID- 30294135
TI  - Hepatitis A Virus-induced Severe Hemolysis Complicated by Severe Glucose-6
      Phosphate Dehydrogenase Deficiency.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an x-linked recessive
      genetic disorder with mutation in the G6PD gene. Defect in the enzyme G6PD causes
      red blood cells (RBCs) to breakdown prematurely causing hemolytic anemia.
      Hemolytic anemia is also a known hematological complication associated with viral
      hepatitis. In such patients, hemolysis may be more severe if there is any
      secondary injury to RBC in the form of membrane defect, oxidative stress, or
      enzyme deficiency like in G6PD deficiency. Here, we present a case of an adult,
      not previously diagnosed with G6PD deficiency, who presented with viral
      hepatitis, severe hemolysis, and multiorgan failure.

PMID- 30294136
TI  - Severe Hypokalemia Mimicking Brain Death.
AB  - We discuss a case of a 20-year-old female who presented with history of fever,
      vomiting, and decreased oral intake for 10 days followed by one episode of
      generalized tonic-clonic seizure and altered sensorium for 5-6 h. On arrival in
      the emergency room, she had Glasgow Coma Scale 3 (E1V1M1), both pupils fixed and
      dilated, low blood pressure, low oxygen saturation, and few gasping breaths. She
      appeared to be brain dead and was assumed to have a very poor prognosis.
      Investigations revealed severe hypokalemia. She had also suffered acute hypoxic
      ischemic injury to the brain. However, she recovered and was discharged about 2
      weeks later.

PMID- 30294137
TI  - A Rare Case of Localized Tetanus.
AB  - Tetanus is a severe and potentially fatal infection caused by the bacterium
      Clostridium tetani. Presentations of tetanus include generalized tetanus,
      neonatal tetanus, cephalic tetanus, and localized tetanus, the latter two being
      much rarer. We present case of a 55-year-old male farmer, presented with an
      injury to the left toe. A surgical wound exploration and washout with
      administration of human tetanus immunoglobulin and tetanus toxoid were given as
      treatment with antibiotic support. This case report points out the importance of
      the early recognition of a rare form of this fatal infectious disease, which may
      present with prodromal symptoms before the generalized form shows its clinical
      effects. Successful management includes prompt diagnosis, neutralization of
      circulating toxin and elimination of C. tetani infection, control of spasms,
      maintenance of the airway, and management of respiratory failure and autonomic
      dysfunction.

PMID- 30294138
TI  - Verapamil as an Adjuvant Treatment for Drug-Resistant Epilepsy.
AB  - Almost one-third of the people suffering from epilepsy continue to have seizures
      in spite of using appropriate antiepileptics. Pharmacoresistance is defined as
      the failure to achieve seizure control with two or more anticonvulsant
      medications at appropriate daily dosage. Here, we discuss one such gentleman
      whose seizures had been intractable despite multiple antiepileptic drugs in
      maximum tolerable doses. Verapamil, a calcium channel blocker, was used for its P
      glycoprotein inhibition properties to overcome the pharmacoresistance in this
      patient with satisfactory seizure control. There are a few studies with limited
      patients on the successful usage of verapamil in a patient with pharmacoresistant
      status epilepticus (SE). We intend to publish this case report to draw interest
      among the critical care physicians on pharmacoresistant SE, the different
      hypotheses that prevail, its causes and the available management strategies.

PMID- 30294139
TI  - Speech and Swallowing Function Outcome Following Early Tracheostomy in Patients
      Who Underwent Neurosurgical Intervention.

PMID- 30294140
TI  - Echographic Comparison of Optic Nerve Sheath Diameter between Both Eyes.

PMID- 30294141
TI  - Organ Donation Rate in Brain-Dead Patients in a Tertiary Referral Center.

PMID- 30294143
TI  - Competence and Transformation of Oral Streptococcus sobrinus in Dental Caries.

PMID- 30294142
TI  - Government Policy, Clean Fuel Access, and Persistent Fuel Stacking in Ecuador.
AB  - After more than three decades of access to low-cost liquefied petroleum gas (LPG)
      financed by large direct government subsidies, more than 90% of Ecuadorian
      households cook primarily with LPG. Due to the large fiscal burden of the LPG
      subsidy, increases in electricity from hydropower, and other sociopolitical
      factors, the Government of Ecuador launched a major induction stove program (PEC)
      to reduce the demand for LPG. We assess the effects of the LPG subsidies and PEC
      using government records, interviews, academic literature, newspaper reports,
      household surveys, and focus groups. Household surveys, conducted in rural,
      northern Ecuadorian households (n=383), characterized cooking patterns and fuel
      access. Focus groups (n=6) were carried out with a subset of surveyed households
      to better characterize survey findings. The LPG subsidy was developed as part of
      broad social support reforms in the early 1970s, without specific aims to reduce
      the health impacts of household air pollution from woodfuel or provide economic
      benefits as part of the transition to a clean cooking fuel. Nonetheless, the
      subsidy has resulted in nearly all Ecuadorian households cooking primarily with
      LPG. PEC has generated the sale of 740,000 induction stoves since its inception
      in 2014, short of the goal of 3.5 million. Among the rural households surveyed,
      LPG use, acceptance, and satisfaction was high, however, more than three-quarters
      of those surveyed reported weekly woodfuel use. Induction stove ownership (17%)
      and use as a primary cooking fuel (1%) was low among the rural households
      surveyed; furthermore, households owning induction stoves reported very low
      satisfaction with the stoves. Here we show that nationally-representative surveys
      reporting only "primary cooking fuef" use may underestimate solid fuel use as a
      supplemental household cooking energy, particularly in rural areas where fuel
      availability issues play a stronger role in decisions about what fuels to use.

PMID- 30294144
TI  - A Comparison of Oral Midazolam-ketamine, Dexmedetomidine-fentanyl, and
      Dexmedetomidine-ketamine Combinations as Sedative Agents in Pediatric Dentistry:
      A Triple-Blinded Randomized Controlled Trial.
AB  - Introduction: It is common to encounter a patient who is anxious to the magnitude
      that precludes the possibility of provision of dental treatment. This study aims
      to evaluate and compare the sedative effect of oral combinations of midazolam
      ketamine (MK), dexmedetomidine-fentanyl (DF), and dexmedetomidine-ketamine (DK)
      in a group of uncooperative children requiring dental treatment. Methodology:
      This was a prospective, randomized, triple-blind study where 36 children who were
      3-9 year old with American Society of Anesthesiologists -I status and presenting
      early childhood caries were randomly assigned to: Group A - 0.3 mg/kg of M and 5
      mg/kg K, Group B - 2 ug/kg of D with 3 ug/kg of F, and Group C - 2ug/kg of D with
      5 mg/kg of K in 1 mL honey. Patients' blood pressure, heart rate, and oxygen
      saturation were recorded from the start of the procedure till discharge.
      Patients' behavior, sedation status, and wake-up behavior were evaluated with
      Modified Observer Assessment of Alertness and Sedation Scale and ease of
      treatment completion by Houpt scale. Results: Hemodynamic changes were
      statistically insignificant in all three groups. 72.8% of patients in Group A and
      58.3% of patients in Group B were successfully sedated during treatment. Behavior
      improvement was seen in all three groups during treatment with statistically
      insignificant difference in behavior scores produced by Group C. Ease of
      treatment completion was moderately better with Group A. Conclusion: Oral DK has
      a comparable sedative property with oral MK combination. Oral DF promises to be a
      potential sedative agent for children due to its successful anxiolysis.

PMID- 30294145
TI  - Comparative Evaluation of Antimicrobial Efficacy of Silver Nanoparticles and 2%
      Chlorhexidine Gluconate When Used Alone and in Combination Assessed Using Agar
      Diffusion Method: An In vitro Study.
AB  - Context: Silver nanoparticle (AgNP) is a potent antimicrobial that is widely used
      in several fields of medicine. Chlorhexidine (CHX) gluconate is a well-known
      agent used in dentistry to eliminate oral microbial flora. Aims: The aim of this
      study is to evaluate the efficacy of AgNPs, 2% CHX gluconate, and the combination
      of two solutions against endodontic pathogens such as Enterococcus faecalis,
      Klebsiella pneumoniae, and Candida albicans. These organisms are frequently found
      in the root canal space and their persistence may lead to endodontic failure. The
      synergistic effect of the two solutions has been evaluated in this study. The
      antibiotic gentamycin was taken as the control group. Settings and Design: Agar
      well diffusion method was used and minimum inhibitory concentration of AgNP was
      found to be 15 MUg/mL. AgNPs were synthesized from the aqueous plant extract of
      Cassia roxburghii. The combination of CHX-AgNP solution was stirred together by a
      glass rod. The values were tabulated and subjected to statistical analysis using
      the SPSS software version 20. One-way ANOVA test was used to compare within the
      groups and between groups. The level of significance was set at 5%. Results: CHX
      AgNP combined solution exhibited the highest efficacy in comparison to these
      solutions used alone. They showed the highest efficacy against C. albicans among
      the three organisms tested. Conclusion: The present study demonstrates the
      antimicrobial efficacy of a novel mixture of CHX-AgNP solution, and it may be
      developed as a promising antimicrobial agent against endodontic flora.

PMID- 30294146
TI  - Evaluation of Serum Leptin and Adiponectin in Obese Individuals with Chronic
      Periodontitis.
AB  - Objectives: Studies have reported changes in leptin and adiponectin levels in the
      gingival crevicular fluid, saliva, and blood serum of obese patients with
      periodontal disease. The aim of the study is to evaluate serum leptin and
      adiponectin levels in obese and nonobese individuals with chronic periodontitis
      and to deduce a relationship between the clinical parameters and the inflammatory
      biochemical parameters. Materials and Methods: In this case-control study, a
      total of fifty individuals were selected based on the body mass index (BMI):
      Group I of obese individuals with chronic periodontitis and Group II of nonobese
      individuals with chronic periodontitis. Periodontal parameters used in this study
      were plaque index, gingival index, probing pocket depth, and clinical attachment
      level. The effects of obesity and periodontal status on serum leptin and
      adiponectin levels of both groups were statistically analyzed using an
      independent t- test. Results: Statistical analysis showed that the effect of BMI
      on serum leptin and adiponectin levels was statistically significant (P < 0.01),
      and the effect of chronic periodontitis on the serum leptin and adiponectin
      levels was also statistically significant compared to nonobese individuals (P <
      0.0001). However, there is no statistically significant correlation between serum
      leptin and adiponectin, which indicates that both are independent to each other.
      Conclusions: In obese individuals with chronic periodontitis, serum leptin levels
      were significantly high compared to nonobese individuals and serum adiponectin
      levels were significantly lower in obese individuals compared to nonobese
      individuals with periodontitis, though both the parameters were independent of
      each other.

PMID- 30294147
TI  - Comparative Evaluation of Apical Transportation and Canal Centric Ability in
      Apical Region of Newer nickel-titanium File Systems Using cone-beam computed
      tomography on Extracted Molars: An In Vitro Study.
AB  - Background: Objective in root canal preparation is to develop a shape that tapers
      from apical to coronal, maintaining the original canal shape. With advent of
      instruments manufactured from nickel-titanium (NiTi) alloys, there was a
      significant improvement of quality of root canal shaping, with predictable
      results and less iatrogenic damage. Aim: The aim of the study was to evaluate the
      canal centric ability and apical transportation in apical region of newer NiTi
      file system in root canal using cone-beam computed tomography (CBCT) on extracted
      molars. Materials and Methods: Root canal of thirty extracted human permanent
      teeth with mature root apices with 20 degrees -40 degrees  of curvature were
      collected and divided into three groups after initial bio-mechanical preparation:
      Group 1: canal prepared using ProTaperNext (PTN) file system; Group 2: canal
      prepared using Mani silk system; and Group 3: canal prepared using V-taper file
      system. All samples were scanned before and after biomechanical preparation using
      CBCT. The data collected were evaluated using the Kruskal-Wallis analysis of
      variance test and Mann-Whitney U-test. Results: It was observed that in apical
      region Group I (PTN) showed significantly lower mean apical transportation and
      canal centric ability as compared to Group II (Mani Silk) and Group III (V
      taper). Conclusion: It was concluded that PTN rotary system has no canal
      transportation and maintained centric ability in comparison to Mani and V-taper
      rotary file system in apical region of curved root canal.

PMID- 30294148
TI  - Prevalence of Pneumatized Articular Tubercle Using Panoramic Radiography and Cone
      Beam-Computed Tomography: A Retrospective Study.
AB  - Context: In 1985, Tyndall and Matteson first described the air cells that occur
      in the root of zygomatic arch and in the articular eminence of the temporal bone
      but do not extend beyond the zygomaticotemporal suture. Aims: The aim is to study
      the prevalence and patterns of pneumatized articular tubercle (PAT)
      retrospectively using two different imaging modalities, i.e., digital panoramic
      radiography and cone-beam computed tomography (CBCT). Subjects and Methods: Total
      3000 panoramic radiographs belonging to 1291 females and 1709 males and CBCT
      scans of 200 patients belonging to 62 females and 138 males were studied
      retrospectively and investigated for radiographic features of pneumatized
      articular tubercle. Results: Prevalence found by using panoramic radiography is
      1.96% and by using CBCT is 12.5%. Conclusions: This research scrutinizes the
      prevalence of pneumatized articular tubercle and establishes the prevalence of
      the same among the studied population, using panoramic radiography and CBCT.

PMID- 30294149
TI  - Evaluation of Antimicrobial Efficacy of Nanosilver Solution, Sodium Hypochlorite
      and Normal Saline in Root Canal Irrigation of Primary Teeth.
AB  - Background: Bacteria are the main etiological factors in the development of
      dentinal caries and its progression to pulpal and periapical disease.
      Enterococcus faecalis is the bacterial species most frequently recovered from the
      root-filled teeth. Aim: This study aimed to evaluate the antimicrobial
      effectiveness of nanosilver (NS) solution as an endodontic irrigation solution of
      primary teeth against E. faecalis. Settings and Design: Thirty-six canals of
      primary teeth were selected for this ex vivo study. Methods and Materials: Thirty
      six canals of primary teeth were prepared up to the file #35 and all of the
      specimens were sterilized. Then, root canals were inoculated with a suspension
      containing E. faecalis bacteria. The teeth were then randomly divided into three
      groups. Antimicrobial effectiveness was evaluated immediately after dividing into
      groups by counting colony-forming units on brain heart infusion broth plates.
      Statistical Analysis: Data were analyzed using Kolmogorov-Smirnov, Welch, and
      Dunnett's T3 tests. Results: Sodium hypochlorite showed the highest antimicrobial
      effectiveness against E. faecalis and showed significant differences compared
      with normal saline and NS solution (P < 0.001). Conclusion: Based on the results
      of this study, solution of NS particles can be used as an alternative to other
      root canal irrigating solutions.

PMID- 30294150
TI  - Comparative Evaluation of Retention, Cariostatic Effect and Discoloration of
      Conventional and Hydrophilic Sealants - A Single Blinded Randomized Split Mouth
      Clinical Trial.
AB  - Introduction: Pit and fissures are approximately eight times vulnerable than the
      smooth surface caries lesion. Sealants are effective in preventing, arresting,
      and progression of pit-and-fissure occlusal caries lesions. The failure of
      sealant resin-based retention is mainly attributed to the moisture contamination.
      To overcome this drawback, UltraSeal XT(r) hydro, a moisture-friendly sealant,
      has been introduced. Aim: This study aimed to compare and evaluate the retention,
      cariostatic effect, and discoloration of conventional ClinproTM 3MTM ESPETM and
      hydrophilic UltraSeal XT(r) sealants among 12 to 15-year-old schoolchildren for 3
      months. Materials and Methods: A single-blinded, randomized, split-mouth clinical
      trial was conducted among thirty schoolchildren aged 12-15 years. Sealants used
      in the present study were Group I - ClinproTM and Group II - UltraSeal XT(r)
      hydro. Sealants were provided in the school by two operators based on the
      computer-generated random sequence and the study participants were evaluated
      after 3 months for sealant coverage, caries incidence, and discoloration using
      Color, Coverage and Caries sealant evaluation system. Sealant coverage between
      the two sealants was compared using Mann-Whitney U-test and Z-test for
      proportions. Results: A total of 47 teeth (78.3%) with UltraSeal XT(r) Hydro had
      the sealant covering in all the fissures compared to ClinproTM 3MTM ESPETM which
      was 46.7% (28 teeth) and the difference was observed to be statistically
      significant. Conclusion: Hydrophilic UltraSeal XT(r) Hydro yielded better sealant
      coverage (retention) compared to the conventional ClinproTM 3MTM ESPETM. No
      difference was observed with regard to cariostatic effect and discoloration.

PMID- 30294151
TI  - Evaluation of Marginal Adaptation of a Self-Adhering Flowable Composite Resin
      Liner: A Scanning Electron Microscopic Study.
AB  - Background: "Self-adhering composite resins," are claimed to eliminate the need
      for a separate acid etching and bonding agent application step, thus simplifying
      the direct restorative procedure, both regarding the technique sensitivity and
      the duration of treatment. Aim: The aim of this study is to evaluate the marginal
      adaptation of self-adhering flowable composite (Dyad flow) in comparison to the
      conventional flowable composite (Tetric N-flow) under scanning electron
      microscope (SEM). Settings and Design: This in vitro study was conducted on 44
      extracted human maxillary premolars. Materials and Methods: Box-only Class II
      cavities on the distal surface were prepared with the dimensions of 4 mm
      buccolingual width, 2 mm mesiodistal depth, and gingival margin at the
      cementoenamel junction. They were divided into two groups of 22 teeth each and
      were restored accordingly: Group I - Gingival floor lined with Tetric N-Flow and
      were restored with Tetric N-Ceram; Group II - Gingival floor lined with Dyad flow
      and were restored with Herculite Precis. After thermal cycling, the sectioned
      tooth-restoration interfaces were evaluated for the marginal adaptation under SEM
      at *200 magnification. Statistical Analysis Used: The resultant data were
      statistically analyzed by applying Chi-square test, using the SPSS (version 16.0)
      software. Results and Conclusion: There was no statistically significant
      difference between the study groups regarding the marginal adaptation. The
      marginal adaptation of the self-adhering flowable composite when used as a liner
      in Class II restorations was comparable to that of the conventional flowable
      composite.

PMID- 30294152
TI  - Molar Incisor Hypomineralization and Its Prevalence.
AB  - Background: Molar incisor hypomineralization (MIH) is the hypomineralization of
      systemic origin of one to four permanent first molars, frequently associated with
      affected incisors. It is presented as demarcated enamel opacities of different
      colors, occasionally undergoing posteruptive breakdown. The characteristic
      feature of MIH is the clear demarcation between the affected and sound enamel.
      There is asymmetry of defects present in the molars and incisors where one molar
      or incisor can be severely affected, while the contralateral tooth may be
      clinically sound or have only minor defects. Aim and Objective: The aim of this
      study is to evaluate schoolchildren of 7-12 years of age with at least one of the
      first permanent molars fully or partially erupted from randomly selected
      government and private schools in Chennai using the European Academy of Pediatric
      Dentistry (EAPD) criteria for MIH, to determine the prevalence and
      characteristics of MIH. Materials and Methods: The dental examinations were
      performed in the classroom using a mouth mirror and explorer under a headlight.
      Teeth were wiped with gauze when necessary to remove plaque or the food
      accumulations. Surfaces that were examined were the buccal, lingual, palatal, and
      occlusal surfaces of permanent first molars and labial surfaces of upper and
      lower incisors. A single examiner was involved to avoid interexaminer bias. All
      the data were collected and scored using the EAPD criteria for MIH. Results: A
      total of 22 (12.9%) children out of the examined 170 had MIH. Conclusion:
      Distribution of MIH was more in males, more in 9 years of age. A total of 13
      children had first molars affected and 9 children had both incisors and molars
      affected. Molars were affected more than the incisors. Mandible was affected more
      in comparison with the maxilla. Right side was affected more than the left side.
      The distribution of MIH was more in government schools compared to private
      schools.

PMID- 30294153
TI  - Physical Properties of Heat Cure Denture Base Resin after Incorporation of
      Methacrylic Acid.
AB  - Introduction: Heat cure acrylic resins are the most commonly used denture base
      materials. The important limitation is they may act as reservoir of
      microorganisms. The adherence of microorganisms can be reduced by chemical
      modification of the surface charge of denture base resin. Incorporation of
      methacrylic acid (MA) in the denture base resin gives a negative surface charge.
      A denture base having a negative surface charge may hinder the initial adhesion
      of microorganisms through repulsive electrostatic forces. Aims and Objectives:
      The present in vitro study was performed to determine the effect of addition of
      antimicrobial agent MA on the flexural strength and surface roughness of heat
      cure denture base resin. Materials and Methods: A total of 90 heat cure acrylic
      specimens were prepared. Of 90 specimens, 30 were prepared as Group I control
      group without addition of MA. Groups II and III specimens were prepared by adding
      10% and 20% MA, respectively. Using universal testing machine and surface
      roughness tester, flexural strength and surface roughness of specimens measured.
      Results: In the present study, decrease in the flexural strength was observed
      when the concentration of the MA increased in the denture base resin. A slight
      increase in the surface roughness was observed as the concentration of MA
      increased.

PMID- 30294154
TI  - Burning Mouth Syndrome: A Comparative Cross-sectional Study.
AB  - Background and Aim: Burning mouth syndrome (BMS) may be defined as a burning
      sensation in the oral mucosa usually unaccompanied by clinical signs. Multiple
      conditions have been attributed to a burning sensation. The aim of this study was
      to determine the role of age and sex in BMS. Materials and Methods: A total of
      195 consecutive patients with BMS and 95 healthy patients without burning
      sensation were recruited in this study. Patients with BMS had experienced oral,
      burning sensations for at least 6 months without oral clinical signs, and with a
      normal blood count. Multiple logistic regression analyses were utilized to define
      the main predictors. Results: Menopause, candidiasis, psychological disorders,
      job status, denture, and dry mouth were significantly frequent in BMS patients.
      Multivariate logistic regression indicated age (odds ratio (OR) =1.12, 95%
      confidence interval (CI): 1.08-1.15, P < 0.0001) and sex (OR = 3.14, 95% CI: 1.4
      6.7, P < 0.002) significantly increase the odds of BMS. Psychological disorders
      (OR = 3.39, 95% CI: 1.2-9.5, P < 0.02) and candidiasis remain as predictive
      factors. Ultimately, age was defined as a critical predictor. Moreover, we can
      therefore predict that a 60-year-old woman with psychological disorders is 25
      times more likely to suffer from BMS than a man 10 years younger who has no
      psychological disorder. Conclusion: Age and sex were the main predictors in BMS.
      Psychological disorders and candidiasis were significantly associated with the
      occurrence of BMS.

PMID- 30294155
TI  - Comparative Study of the Effect on Apical Sealability with Different Levels of
      Remaining Gutta-Percha in Teeth Prepared to Receive Posts: An in vitro Study.
AB  - Objective: The objective of this study is to compare the apical sealability of
      mineral trioxide aggregate (MTA) Fillapex and Endosequence BC sealer at three
      different lengths of remaining gutta-percha after postspace preparation.
      Materials and Methods: A total of 80 freshly extracted human maxillary anterior
      teeth were decoronated, biomechanically prepared, and randomly divided into four
      groups; Group A and Group B served as positive and negative control with 10 teeth
      each. The teeth in Group C and Group D (with 30 teeth each) were obturated with
      gutta-percha using MTA Fillapex sealer and Endosequence BC sealer, respectively.
      Teeth in Group C and Group D were further subdivided into three subgroups
      depending on the length of remaining apical gutta-percha, i.e., 3, 4, and 5 mm
      after postspace preparation. Apical leakage was assessed using dye penetration
      method under stereomicroscope. Results: In both the Groups C and D, there was
      overall no statistically significant difference in leakage; however, Group C
      showed slightly more leakage than Group D. There was a statistically significant
      difference in leakage at 3 mm and 5 mm level in both groups. Conclusion: Although
      less microleakage occurred, the bioceramic sealers could not totally eliminate
      leakage.

PMID- 30294156
TI  - Effect of Preetching on Microleakage with All-In-One Adhesives Using Calcium
      Based Desensitizers: An In vitro Study.
AB  - Objectives: The aim of this study was to evaluate the effect of calcium-based
      desensitizers on the microleakage with and without preetching enamel in Class V
      cavities restored with all-in-one adhesives. Materials and Methods: Class V
      cavities were prepared on the buccal surfaces of 100 extracted human premolars. A
      total of 100 box-shaped cavities were divided into five groups (n = 20). Group 1 
      no desensitizer was applied and Groups 2 and 4 - desensitizer (CCP-ACP and
      Novamin) was applied, respectively, followed by the application of G-Bond and
      restored with composite restoration. Groups 3 and 5 are same as Group 2 and 4,
      but preetching of enamel was done for 3 s after desensitizers application. The
      teeth were thermocycled and the specimens were examined for microleakage using
      methylene blue as a marker. The teeth were sectioned buccolingually and evaluated
      for microleakage under stereomicroscope and the scores obtained were analyzed
      with Kruskal-Wallis and Mann-Whitney tests. Results: Statistically significant
      difference existed between Groups 2 and 3 (P < 0.05). There was also
      statistically significant difference between Groups 4 and 5 (P < 0.05). Groups 3
      and 5 showed significantly less microleakage (P < 0.05). No statistically
      significant difference in microleakage values was observed between the two
      desensitizers CCP-ACP and Novamin. Conclusion: The application of calcium
      containing desensitizers with selective etch enamel technique in all-in-one
      adhesives could be considered an advisable procedure to minimize microleakage.

PMID- 30294157
TI  - Efficacy of Intraosseous Local Anesthesia for Restorative Procedures in Molar
      Incisor Hypomineralization-Affected Teeth in Children.
AB  - Background: Treatment of teeth affected with molar incisor hypomineralization
      (MIH) in young patients is challenging due to chronic subclinical pulpal
      inflammation caused by porous enamel and exposed dentin. Hypersensitivity of the
      teeth and difficulty in achieving local anesthesia due to altered nerve potential
      affects the successful completion of the treatment. Aim: The aim of the study was
      to compare the anesthetic efficacy of the intraosseous (IO) anesthetic technique
      with conventional local infiltration technique in anesthetizing first permanent
      molars (FPMs) affected by MIH for restorative procedures in children. Materials
      and Methods: This randomized controlled clinical trial recruited 54 MIH-affected
      mandibular or maxillary FPMs requiring restorations or stainless steel crowns.
      The teeth were randomly allocated to two equal groups to receive either IO
      injection or buccal infiltration (control), both using 4% articaine. Onset, time
      required, and pain experienced for administration, need for repeat, efficacy of
      anesthetic technique, heart rate, and postoperative complications were recorded
      in both the groups. Collected data were subjected to statistical analysis.
      Results: Onset was significantly faster and pain experienced during
      administration was significantly lower with IO technique. Need for repeat of
      anesthesia was significantly more with infiltration (44.4% vs. 7.4% in IO, P =
      0.004). Local infiltration failed to produce profound anesthesia in 74.1% MIH
      affected teeth. IO anesthesia profoundly anesthetized 88.9% MIH-affected teeth.
      Anesthetic efficacy was significantly better with IO anesthesia (P < 0.001).
      Postoperative complications were significantly lower with IO anesthesia (P =
      0.003). Conclusion: IO local anesthesia was found to be an effective and safe
      technique to achieve profound anesthesia in MIH-affected teeth in children in
      comparison to local infiltration.

PMID- 30294158
TI  - Assessment of Survival Rate of Dental Implants in Patients with Bruxism: A 5-year
      Retrospective Study.
AB  - Background: Dental implants are associated with failure such as early or late
      failure. Systemic conditions such as diabetes, hypertension, and bruxism affect
      the success rate. The present study was conducted to assess complications in
      dental implants in bruxism patients. Materials and Methods: This 5-year
      retrospective study was conducted on 450 patients (640 dental implants) who
      received implants during the period and followed up for 5 years from June 2010 to
      June 2016. Among these patients, 124 had bruxism habit. Dental radiographs or
      patients' recalled records were evaluated for the presence of complications such
      as fracture of implant, fracture of ceramic, screw loosening, screw fracture, and
      decementation of unit. Results: In 240 males and 210 females, 380 implants and
      260 implants were inserted, respectively. The difference was statistically
      nonsignificant (P = 0.1). A total of 145 screw-type and 130 cemented-type
      fixations had complications. The difference was statistically nonsignificant (P =
      0.5). Complications were seen in single crown (45), partial prostheses (125), and
      complete prostheses (105). The difference was statistically significant (P =
      0.012). The common complication was fracture of ceramic (70) in cemented-type
      fixation and fracture of ceramic (85) in screw-type fixation. The difference was
      statistically significant (P = 0.01). Forty-two single crowns showed
      decementation, 85 partial prostheses had fracture of ceramic/porcelain, and 50
      complete prostheses showed fracture of ceramic/porcelain. The failure rate was
      42.9%. Survival rate of dental implants in males with bruxism habit was 90% after
      1 year, 87% after 2 years, 85% after 3 years, 75% after 4 years, and 72% after 5
      years. Survival rate of dental implants in females with bruxism habit was 92%
      after 1 year, 90% after 2 years, 85% after 3 years, 75% after 4 years, and 70%
      after 5 years. The difference among genders was statistically nonsignificant (P =
      0.21). Conclusion: Bruxism is a parafunctional habit which affects the survival
      rate of dental implants. There is requirement to follow certain specific
      protocols in bruxism patients to prevent the developing complications.

PMID- 30294160
TI  - Dermatoglyphic Analysis in Parents with Cleft Children: A Comparative Study.
AB  - Background and Objective: There were studies in the literature which showed the
      altered dermatoglyphics in the cleft children. But it would be beneficial if
      probable expression can be proved in prior generations, so that genetic
      counseling and other preventive measures can be undertaken. The aim of the study
      is to determine variations in dermatoglyphics of prior generations which would
      serve as bench markers to predict the occurrence of cleft in off springs.
      Materials and Methods: A total of 400 parents aged between 25-45 years were
      selected and divided into two groups - Group A consisted of parents with cleft
      children and Group B comprised of parents with at least 2 healthy children who
      met the inclusion criteria. Dermatoglyphic prints were collected by ink method
      and evaluated for pattern types, total ridge count and palm prints were evaluated
      for a-b ridge count, atd angle and asymmetry. Results: Significant difference was
      observed between Group A and B with reference to pattern types; TRC and a-b ridge
      count and atd angle. Absence of t point was variably noticed in the mothers of
      affected children. Conclusion: Dermatoglyphics can be used as tool to study the
      developmental instability of cleft anomalies and provides data to assess the
      genetic etiology of clefting.

PMID- 30294159
TI  - Effect of Laser Etching and Spark Erosion on Retention and Resistance of Partial
      Veneer Crown Copings Luted with Adhesive Resin Cement.
AB  - Purpose: There has been less focus on methods to improve the clinical performance
      of partial veneer crowns. In this study, we wanted to explore the potential of
      two new surface treatment modalities (laser etching and spark erosion) for
      improving the longevity of partial veneer crowns. Material and Methods:
      Conventional partial veneer crown preparation was done on 90 extracted premolars
      by a single operator. All the samples used in the study were divided into three
      groups. Group A were samples to be treated by sandblasting alone, Group B were
      samples to be treated by sandblasting followed by laser etching, and Group C were
      samples to be treated by sandblasting followed by spark erosion. Each group
      consisted of two Sub Groups: Sub Group I-Retention test group, Sub Group: II
      Resistance test group. The prepared teeth were randomly allotted to the three
      groups and subgroups using lot method. Partial veneer crown copings were
      fabricated for testing retention and resistance. Castings in each subgroup were
      luted with resin cement to their respective tooth preparations. Retention and
      resistance testing of samples were done with the use of an Instron Universal
      testing machine. Results: The two surface treatments, laser etching and spark
      erosion (Groups B and C) of metal copings significantly improved the retention
      and resistance compared to sandblasted surfaces alone (P <= 0.05). Retention and
      resistance of copings which were sandblasted and spark eroded (Group C) were
      found to be highest among the three groups (P <= 0.05). Conclusion: Within the
      limitation of this study, it can be concluded that the combination of spark
      erosion and sandblasting significantly improves the retention and resistance
      values of partial veneer crown. This study helps to provide better knowledge
      about the surface treatment required for success of partial veneer crowns.

PMID- 30294161
TI  - Association of Stress, Salivary Cortisol, and Chronic Periodontitis: A Clinico
      biochemical Study.
AB  - Background: Periodontitis and stress are among the areas of increasing interest
      over the past two decades. Early detection of these diseases plays a crucial role
      in successful therapy. Cortisol is a protein which was found to be consistently
      associated with both. Aim: The present study was aimed to evaluate saliva
      cortisol levels (SCLs) in chronic periodontitis (CP) patients with and without
      stress. Materials and Methods: In this cross-sectional study, saliva samples were
      collected and cortisol levels were determined using ELISA method in 92
      participants. The participants were divided into four groups based on periodontal
      condition (number of teeth present, plaque index (PI), bleeding on probing (BOP),
      probing pocket depth, and clinical attachment level) and stress levels into Group
      1 (no periodontitis and no stress), Group 2 (with periodontitis and no stress),
      Group 3 (without periodontitis and with stress), and Group 4 (with periodontitis
      and stress). Results: Overall, 92 adult participants (41 males and 51 females)
      were included in the study. Participants with stress and periodontitis have high
      mean SCL when compared to other groups (Group 1: 15.01 +/- 2.62, Group 2: 31.92
      +/- 6.80, Group 3: 34.47 +/- 13.47, and Group 4: 60.13 +/- 6.68). Group I shows a
      significant negative correlation of cortisol to BOP, stress to PI, and stress to
      cortisol level, whereas there is a positive correlation of SCL to PD in Group 4
      which is not statistically significant. Conclusion: SCL showed difference among
      the groups. SCL were associated with both CP and psychological stress. Increase
      in inflammation and stress levels enhances the SCL.

PMID- 30294162
TI  - Unrevealed Caries in Unerupted Teeth: A Prevalence Study.
AB  - Background: Preeruptive caries are an abnormal, well-circumscribed, radiolucent
      area, occurring within the coronal dentinal tissue close to the dentinoenamel
      junction of unerupted teeth. OPGs are commonly taken in children for assessing
      the dental age and eruption sequence. It can be used as a good diagnostic source
      for detection of PEIR defects. Aim: The aim of this study is to determine the
      prevalence of Preeruptive intracoronal dentin radiolucencies in unerupted
      permanent teeth from orthopantomogram. Settings and Design: A total of 1000
      standard orthopantomographs of children below 12 years of age were collected and
      examined. Methodology: The OPGs were examined for PIER defects in the unerupted
      teeth. The prevalence of PEIR defects was assessed with respect to age, sex,
      tooth, and the arch involved. Statistical Analysis: The data obtained were
      tabulated and analyzed. The prevalence was calculated in percentage. Results: The
      participant prevalence was 13.6%. The teeth prevalence was 1.20%. The majority
      (38.9%) of defects were seen in the in the mandibular first premolar. Almost half
      of the lesions were located on the mesial side (52.3%), with a size less than one
      third of dentine thickness (53%). Conclusion: PIER defects constitutes an
      important part of anomalies associated with unerupted teeth and thus needs a
      proper understanding of its prevalence, etiology, manifestations, and
      complications. These defects are usually overlooked by clinicians while
      interpreting radiographs; however, it is of utmost importance to promptly
      diagnose these defects thus preventing further complications.

PMID- 30294163
TI  - Candidal Species Identification in Malignant and Potentially Malignant Oral
      Lesions with Antifungal Resistance Patterns.
AB  - Objective: Candidal species identification in malignant and potentially malignant
      oral lesions with antifungal susceptibility. Materials and Methods: Oral candidal
      carriage, strain diversity, and antifungal susceptibility of Candida were checked
      for the patients having oral cancer or precancer reporting to the clinics for
      11/2 year. Statistically significant patients were selected and a control group
      was taken. A total of 105 individuals were selected and divided into three
      different groups. Salivary samples were taken from all the individuals. Candida
      detection was done using Sabouraud's agar and candidal species detection on
      CHROMagar. In vitro antifungal sensitivity was done using antifungal disc
      diffusion method. Results: Candida was isolated from 88.6% of patients with oral
      cancer and 45.7% in oral precancerous group. C. albicans was the predominant
      species found in 100% of oral precancerous and 71% in oral cancerous patients.
      Other Candid a species found were C. tropicalis (9.7%) and C. krusei (19.6%).
      Antifungal susceptibility showed 4.3% sensitivity to fluconazole and 100%
      sensitivity to amphotericin B and nystatin. Conclusion: Oral Candida carriage was
      higher in oral cancerous group and majority of them were sensitive to
      amphotericin B and nystatin.

PMID- 30294164
TI  - Dental Caries Experience, Dental Anomalies, and Morphometric Analysis of Canine
      among Monozygotic and Dizygotic Twins.
AB  - Background: The study of twins is a well-known and a unique method that is used
      to investigate the genetic contributions to physical features and diseases in
      human. Aim: To estimate the relative contributions of genetic and environmental
      influence to observed variations in different dental features or traits.
      Methodology: Thirty twins in the age group of 15-30 years were selected for the
      study, and the dental caries experience scores, dental anomalies, and
      morphometric analysis of monozygotic (MZ) and dizygotic (DZ) twins were compared.
      Results: MZ twins unlike DZ twins showed within-pair resemblance in decayed,
      decayed missing and filled teeth (DMFT), and molar relation. No morphometric
      analysis parameters and dental anomalies had significant mean difference between
      the groups. Decay, filling, DMFT, spacing, mandibular irregularity, open bite,
      and mesiodistal width of the right and left canine showed a higher positive
      correlation in MZ than DZ twins. Heritability estimate was low for morphometric
      analysis parameters. There is genetic dominance in decay, DMFT, spacing, molar
      relation, and diastema. Pearson's correlation revealed a positive and
      statistically significant correlation among all morphometric analysis parameters
      for MZ twins, but not DZ twins. Dental caries has a higher concordance rate
      (87.5%), correlation (71.6%), and heritability (87.8%). Conclusion: Most of the
      dental parameters are significantly heritable with up to 85% of the variance
      attributable to genetic factors. Environmental factors play a major role in
      developing malocclusion and causing dental caries. Morphology of canines can be
      used as a supplementary tool to determine zygosity.

PMID- 30294165
TI  - Comparison of Surgical Outcome after Impacted Third Molar Surgery Using Piezotome
      and a Conventional Rotary Handpiece.
AB  - Background and Aim: One of the most commonly performed surgical procedures by
      oral and maxillofacial surgeons all over the world is the removal of impacted
      teeth. The most critical and important steps in third molar extraction are bone
      cutting or osteotomy. Many techniques are used for this purpose including chisels
      and mallet, rotary instruments, and ultrasonic-based bone cutting instruments.
      Piezotome is newer and innovative device for osteotomy based on piezoelectric
      vibrations. Piezotome is considered very efficient in performing osteotomy
      because of its selective cutting; being inert against soft tissues, including
      nerves and blood vessels. The aim of this study was to compare the surgical
      outcome of third molar surgery using conventional handpiece and piezotome with
      all other criteria remaining same for all the individuals. Materials and Methods:
      All patients reporting to the Department of Oral and Maxillofacial surgery,
      Manipal College of Dental Sciences, Mangalore, for impacted mandibular third
      molar removal were screened. A total of 30 patients with same Pederson difficulty
      index for bilateral impacted third molar were selected for the study. The study
      involved the use of piezotome on one side (Side A) and rotary technique (Side B)
      on the other side for osteotomy on the same patient with an interval of 1 month.
      Therapeutic management was same for both the sides. Operating time was recorded
      in each surgery. Patients were examined postoperatively on 1st, 3rd, and 7th day
      and pain, edema, trismus, paresthesia, and dry socket were evaluated and compared
      on both the sides. Data collected were analyzed statistically. Results: The mean
      operating time was 48.13 min in piezotome (Side A) and 32.90 min in conventional
      handpiece (Side B) which was statistically significant (P < 0.001). Furthermore,
      there was statistically significant difference (P < 0.001) in the level of pain
      (P < 0.001), number of analgesics taken (P < 0.001), and trismus (P < 0.01) on
      1st, 3rd, and 7th days postoperatively. There was no statistically significant
      difference in edema between the two sides. Paresthesia was present in one patient
      (3.3%) in Side B, while no paresthesia was present in Side A. No incidence of
      alveolar osteitis was reported on both the sides. Conclusion: Operating time with
      piezotome was more than that of conventional handpiece, but the postoperative
      responses such as pain, trismus, and edema were less in piezotome. Hence, despite
      being a slower procedure, piezotome can be an effective alternative for osteotomy
      in impacted third molar surgery. We recommend using piezotome for bone cutting
      and conventional rotary handpiece for tooth sectioning in order to obtain
      favorable outcomes as well as decreasing the operating time.

PMID- 30294166
TI  - Comparative Evaluation of Antimicrobial Efficacy of Platelet-rich Plasma,
      Platelet-rich Fibrin, and Injectable Platelet-rich Fibrin on the Standard Strains
      of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans.
AB  - Context: Platelet concentrates are commonly used to promote periodontal soft- and
      hard-tissue regeneration. Recently, their antimicrobial efficacy is also
      explored. Various platelet concentrates have evolved which differ in the
      centrifugation protocols. Porphyromonas gingivalis (Pg) and Aggregatibacter
      actinomycetemcomitans (Aa) have been found to have an important role in
      periodontal pathology. Aims: In this study, PRP, PRF, and I-PRF are compared for
      their antibacterial effect against Pg and Aa. Materials and Methods: Blood
      samples were obtained from ten systemically and periodontally healthy
      individuals. Platelet concentrates were prepared using standardized
      centrifugation protocol. Antimicrobial activity was examined on standard strains
      of Pg and Aa using well diffusion method. Statistical Analysis Used: Means for
      the width of zones of inhibition were calculated along with standard deviations,
      and the comparison was made using Wilcoxon signed-rank test. Results: In case of
      Pg, I-PRF had the widest zone of inhibition which was significantly wider as
      compared to PRF. Furthermore, PRP had significantly wider zone of inhibition
      against PRF. In case of Aa, PRP had wider zone of inhibition which was
      significantly wider as compared to that of PRF and I-PRF. Conclusions: All the
      three platelet concentrates PRP, PRF, and I-PRF have antibacterial activity, but
      PRP and I-PRF are more active as compared to PRF. I-PRF being autologous and easy
      to prepare can be a very useful adjunct to the surgical therapy in bringing down
      the bacterial count helping in wound healing and regeneration.

PMID- 30294167
TI  - Comparative Evaluation of Frictional Resistance of Silver-Coated Stainless Steel
      Wires with Uncoated Stainless Steel Wires: An In vitro Study.
AB  - Background: Silver is known for its antimicrobial activity. Silver coating
      effectively reduces Lactobacillus acidophilus and Streptococcus mutans count,
      thus reducing chances of dental plaque and caries. This silver coating may have
      effect on frictional property of orthodontic wires. Aim: The aim of this study is
      to evaluate and compare frictional resistance of silver-coated and uncoated
      stainless steel (SS) wires. Methods: Forty SS wires were divided into four groups
      of 10 each: Group 1 - 0.017 * 0.025 inch SS wires (silver coated), Group 2 -
      0.017 * 0.025 inch SS wires (control), Group 3 - 0.019 * 0.025 inch SS wires
      (silver coated), and Group 4 - 0.019 * 0.025 inch SS wires (control). Surface
      modification of wires was carried out by the thermal vacuum evaporation method
      with silver (10 nm size) using vacuum-coating unit model. The frictional
      resistances of all forty wires were checked on forty 0.022 * 0.028 inch slot
      central incisor brackets (SS wires and brackets from American Orthodontics, St
      Paul, USA) mounted on metal plates using universal testing machine. Results:
      There was no significant difference found in frictional resistance between silver
      coated and uncoated 0.017 * 0.025 inch SS wires group (P = 0.854). Statistically
      significant reduction in frictional resistance was observed in 0.019 * 0.025 inch
      coated SS wires in comparison to uncoated wires (P = 0.032). Conclusion: Overall
      silver coating either did not affect the frictional resistance (0.017 * 0.025
      inch SS wires) or reduced it (0.019 * 0.025 inch coated SS wires) compared to
      uncoated wires. Findings suggest that the use of silver-coated SS wires in
      routine orthodontic practice can be implemented after further in vivo human
      clinical trials.

PMID- 30294168
TI  - Neovascular Pattern in Wound Healing after Zinc Oxide and Curcuma longa Rhizome
      Extract Dressing Application.
AB  - Introduction: Zinc oxide-eugenol dressing is widely used in the dentistry field.
      Eugenol in wound dressing acts as an antibacterial and analgesic agent but known
      to cause hypersensitivity reaction and allergies. Curcuma longa rhizome extract
      could perform as a substitute of eugenol as its active compounds have an anti
      inflammation, antioxidant, anticancer, and antibacterial properties. It has also
      been shown to have proangiogenic and promote wound healing. This study aimed to
      discover the number of neovascular in the wound healing process after the
      application of zinc oxide and C. longa rhizome extract wound dressing. Materials
      and Methods: Full-thickness excision wound of 6 mm * 6 mm was made in the dorsal
      of 32 Wistar strains Rattus norvegicus, before being equally divided into eight
      groups (n = 4): four control groups (C3, C5, C7, and C14) without any dressing
      and 4 treatment groups (T3, T5, T7, and T14) were dressed with zinc oxide and C.
      longa extract wound dressing. The rats consecutively sacrificed on day 3 (C3,
      T3), day 5 (C5, T5), day 7 (C7, T7), and day 14 (C14, T14) to observe the
      neovascular pattern and number using H and E staining. Obtained data were
      analyzed using ANOVA. Results: The neovascular growth in both control and
      treatment groups have the same pattern, while the number of neovascular in
      treatment groups significantly higher than the control groups (P < 0.05).
      Conclusions: Wound dressing combination of zinc oxide and C. longa extract can
      increase the number of neovascular in the wound healing process, while the
      optimum duration of application is 14 days.

PMID- 30294169
TI  - Cephalometric Characteristic of Skeletal Class II Malocclusion in Javanese
      Population at Universitas Airlangga Dental Hospital.
AB  - Introduction: To describe the cephalometric characteristic of skeletal Class II
      malocclusion in Javanese Population at Universitas Airlangga Dental Hospital.
      Methods: A total of 118 lateral cephalograms of preorthodontic patients with
      skeletal Class II malocclusion were obtained from Universitas Airlangga Dental
      Hospital. The lateral cephalograms were analyzed using digital cephalometric
      analysis to determine the ANB, mandibular length, facial axis, Y-axis, sella to
      nasion-mandibular plane (SN-MP), and lower anterior facial height (LAFH).
      Correlation between mandibular length and other variables was analyzed using
      Pearson correlation test with P < 0.05. Results: There was an increase of ANB, Y
      axis, SN-MP, and LAFH. While SNB was decrease and mandibular length was
      shortened. There was a significant correlation between mandibular length and
      other variables, such as facial axis, SN-MP, LAFH, and ANB. Conclusions: Skeletal
      Class II malocclusion in Javanese Population at Universitas Airlangga Dental
      Hospital was characterized by short mandibular length and large ANB mostly not by
      the increased of SNA but by the lack of SNB. The length of mandible correlated
      with facial axis angle, lower anterior facial height, and mandibular plane angle.

PMID- 30294170
TI  - Flexural Strength of Surface-Treated Heat-Polymerized Acrylic Resin after Repair
      with Aluminum Oxide-Reinforced Autopolymerizing Acrylic Resin.
AB  - Background: A fracture of denture base in situ often occurs through a fatigue
      mechanism, which over a period of time leads to the formation of small cracks,
      resulting in fracture. Aim and Objective: To evaluate the flexural strength of
      repaired heat-polymerized acrylic resin, with different percentage of aluminum
      oxide (Al2O3) added to the repair resin and effect of two different surface
      treatments on the flexural strength of repaired heat-polymerized acrylic resin
      and also to evaluate quantification of filler particles using scanning electron
      microscopy. Materials and Methodology: Fifty specimens of heat-polymerized
      acrylic resin were prepared according to the American Dental Association
      specification no. 12 (65 mm * 10 mm * 2.5 mm). Al2O3<50 nm particle size was
      silanized using metal alloy primer before incorporation in polymer. Two different
      percentages of Al2O3 nanoparticles, that is, 1% and 1.5% were added to
      autopolymerizing acrylic resin which was used as repairing material. Results: The
      study showed that repair resin incorporated with 1.5% Al2O3 in the group surface
      treated with silicon carbide paper improved the flexural strength of denture base
      resin. A proper filler distribution and deep penetration within the polymer
      matrix were observed by scanning electron microscope in the same group.

PMID- 30294171
TI  - Assessment of Relation of Orofacial Structures with Pharynx among Males and
      Females: A Lateral Cephalometric Study.
AB  - Aim: This study aimed to determine the correlation between orofacial structure
      and oropharyngeal airway space. Materials and Methods: It comprised of 160
      individuals aged 14-24 years (males: 80 and females: 80), in which digital
      lateral cephalograms were taken. Linear and cephalometric analyses were performed
      in all cases. Results: Ba-PNS, apw2-ppw2, hy-apw2, distance between tongue and
      posterior pharyngeal wall (t-ppw), and Hormion perpendicular and anterior nasal
      spine-posterior nasal spine (ANS-PNS) showed significant difference between males
      and females (P < 0.05). Other distances such as Ba-ad1, Ba-ad2, Ptm-ad1, Ptm-ad2,
      PNS-ppw1, and apw4-ppw4 were statistically nonsignificant (P > 0.05). Conclusion:
      Linear and cephalometric measurements showed that Ba-PNS, t-ppw, Hy-ppw2,
      distance between Ho perpendicular and ANS-PNS plane, and apw2-ppw2 were higher in
      males as compared to females. Lateral cephalograms are useful in orthodontics in
      performing tracings in individuals with a potential risk of malocclusion.

PMID- 30294172
TI  - An Innovative Appliance for the Simultaneous Treatment of Premolar Space Loss and
      Lip Sucking Habit.
AB  - The active lingual arch (LA) and the lip bumper (LB) are popular appliances used
      for maintaining or increasing arch length. This article highlights an innovative
      appliance that incorporates the LA and the LB, indicated for the simultaneous
      treatment of space loss and lip sucking habit.

PMID- 30294173
TI  - Efficacy of Lesion Sterilization and Tissue Repair in Primary Tooth with Internal
      Resorption: A Case Series.
AB  - Lesion sterilization and tissue repair (LSTR) treatment involves the use of a
      triple antibiotic mixture in a suitable vehicle, which is used to disinfect root
      canal systems. This report highlights three cases where LSTR therapy using triple
      antibiotic paste was attempted in primary molars exhibiting gross periradicular
      pathosis and internal resorption. Follow-up examinations revealed reduction of
      periradicular pathosis and reversal of internal resorption in all the three
      cases. This case series opens a perspective on the use of LSTR therapy as an
      alternative option to extraction in treating primary teeth with gross
      periradicular pathosis and internal resorption.

PMID- 30294174
TI  - Rhinoscleroma: Report of an Erratic Palatal Swelling.
AB  - Clinicians come across cases of palatal swellings that present with ambiguous
      features. They may vary in their etiology from numerous infectious and
      noninfectious causes to a wide array of neoplasms. Accurate diagnosis of such
      lesions is vital for their prompt and precise management. Rhinoscleroma (RS), as
      its name suggests, is a persistent, specific, granulomatous disease that results
      in sclerosis of the affected organ - most frequently the nose. Although its
      occurrence in the adjacent sites has been reported, the clinical findings did not
      offer much deviation from the expected. Reported here is a case of RS involving
      the palate which not only detoured from its usual site and course of spread but
      also gave off a confusing facade in terms of its clinical presentation.

PMID- 30294175
TI  - The Efficacy of Low-Level Laser Therapy in Treating Oral Papilloma: A Case
      Reporting A Lingual Location.
AB  - Oral papilloma is a benign proliferation of the stratified epithelium, which
      results in a papillary or verrucous exophytic mass, which can be induced by human
      papillomavirus. These oral mucosa lesions are most often asymptomatic and have
      small progression. Laser-assisted surgery is common nowadays with several
      advantages including successful hemostasis, devoid of sutures, wound
      sterilization and minimal postoperative pain, and edema. The aim of this report
      is to present the oral papilloma in a 40-year-old female patient and its
      treatment with soft-tissue laser. The lesion was excised with diode laser, and
      the healing was uneventful in a follow-up visit after 1 month. Oral papillomas
      can be found in young adult patient's oral cavity, and laser dentistry can be
      used by dental clinicians to treat these kinds of oral lesions and should be
      considered as an alternative to conventional surgery.

PMID- 30294176
TI  - Childhood Pemphigus Vulgaris: Report of Two Cases with Emphasis on Diagnostic
      Approach.
AB  - Childhood pemphigus vulgaris (CPV) is a rare entity with clinical features and
      management primarily similar to those of adults; diagnosis may be difficult due
      to clinical similarity to other disorders such as herpetic gingivostomatitis
      which is more prevalent in this age group. We report two cases of CPV with
      emphasis on diagnostic approach. While treating such patients, it is imperative
      to diagnose CPV in the early stages to prevent serious morbidity and to adjust
      drug dosage to minimize side effects.

PMID- 30294177
TI  - Combined Periodontal-Orthodontic Treatment of Pathologic Tooth Migration: A Case
      Study with 10-Year Follow-Up.
AB  - Pathologic tooth migration is a change in tooth position resulting from
      disruption of the forces that maintain teeth in a normal position in relation to
      their arch. The disruption of the equilibrium in tooth position may be caused by
      various etiologic factors. Loss of attachment apparatus along with a non
      periodontal related condition such as excess occlusal force, a progressive
      migration of tooth may take place. Mostly this migration can be associated with
      aesthetic damage of the smile line. To solve these issues, a combination of
      periodontal and orthodontic treatment is often needed. In this presentation a 23
      year-old, systemically healthy, non-smoking female presented with the complaint
      of bleeding gums, mobility and increased space between upper and lower front
      teeth causing un-aesthetic appearance and low self esteem. She was treated with
      interdisciplinary approach of orthodontic and periodontal intervention.
      Improvement of facial esthetics contributed to the self-confidence of an adult
      periodontal patient with pathologic tooth migration. Follow up at 10 years post
      treatment confirmed the good choice of treatment planning and the tendency to
      improve the results over time. Periodontally compromised orthodontic patients can
      be satisfactorily treated, achieving correction of the malocclusion and a marked
      improvement in esthetics when an interdisciplinary approach is used.

PMID- 30294178
TI  - Surgical Management of Hyperdivergent Class II Malocclusion with Vertical
      Maxillary Excess: A 2-year Follow-up.
AB  - Skeletal Class II malocclusions with vertical maxillary excess (VME) present with
      an amalgamation of several problems pertaining to psychological, esthetics, and
      function. The optimal treatment plan in such cases includes a synchronized
      orthodontic-surgical approach through superior repositioning and setback of
      maxilla by means of Le Fort I osteotomy and augmentation genioplasty. This case
      report describes a multidisciplinary approach in the successful management of a
      patient with VME to achieve superior esthetics and function.

PMID- 30294179
TI  - Surgical Management of Complex Odontoma Associated with Agenesis of a Molar.
AB  - Odontomas are mixed odontogenic tumors composed of mineralized tissue of
      ectomesenchymal origin. These are usually detected in routine radiographs and may
      have a variable etiology such as local trauma, genetic mutation, or infection.
      They are classified into two main types: complex and compound. Complex odontomas
      are rare and they rarely erupt into the oral cavity as they lack periodontal
      ligament. This is the report of one such case of complex odontoma where an 11
      year-old girl reported with an asymptomatic swelling, in relation to the left
      angle of the mandible. The case report highlights the clinical and radiographic
      findings, investigations done to arrive at the diagnosis and the treatment
      rendered. This report is of clinical importance because of its rare association
      with the agenesis of a molar tooth.

PMID- 30294180
TI  - The Metabolic Syndrome and Menopause.

PMID- 30294181
TI  - Analyzing Thyroid Dysfunction in the Climacteric.
AB  - Introduction: Perimenopause and menopause is an integral part of every woman's
      life constituting about 30% of the Indian female population. Hypothyroidism is a
      condition that can mimic menopausal symptoms very often. Therefore, routine
      screening of thyroid function in the climacteric and menopausal period to
      determine subclinical thyroid disease can be recommended. Materials and Methods:
      With this background, we conducted a prospective study in our institute, North
      Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, to
      evaluate the abnormal thyroid function tests in perimenopausal and postmenopausal
      women aged 40-80 years. Results and Observations: Subclinical hypothyroidism
      status increases from the age group of 40-70 years and hypothyroidism increases
      in slow frequency from 40 to 70 years after that there is plateauing.
      Interestingly, the frequency of hyperthyroidism remains same in all the age
      groups. Conclusion: Looking at the increased risks of thyroid disorders with age,
      screening of thyroid disorders can be started at the age of 40 years with
      estimation of serum levels of TSH. This gives us the opportunity to treat both
      subclinical and clinical hypothyroidism and hyperthyroidism women.

PMID- 30294182
TI  - Prevalence of Osteoporosis in Peri- and Post-menopausal Women in Slum Area of
      Mumbai, India.
AB  - Objective: We conducted our study involving 1400 peri- and post-menopausal women
      who live in a slum area of Mumbai to determine the prevalence of osteoporosis,
      awareness about osteoporosis, education (knowledge regarding osteoporosis),
      treatment and prevention of osteoporosis. Material and Methods: A detailed
      medical, surgical, obstetrical & gynecological, menstrual, and drug history was
      recorded in a predesigned questionnaire designated for the study. Height and
      weight and body mass index were measured, physical activity level especially load
      bearing exercise was recorded, and amount of sunlight exposure per day was also
      recorded. Food intake was estimated using the 24 h dietary recall method and
      calcium and Vitamin D consumption pattern was assessed. We used calcaneum
      quantitative ultrasound to assess bone mineral density (BMD) for such large
      population. Results: The prevalence of low BMD was found in more than half of
      this population (81%). The mean age in Group I was found to be 36.50 +/- 2.74
      years as compared to 37.5 +/- 3.44 years in Group II with low BMD, which was
      statistically significant (P = 0.02). The average age at menopause was 51.62 +/-
      5.72 years in Group I and 49.43 +/- 4.52 years in Group II. The number of
      children and type of menopause has been found to be associated with low BMD in
      our study. Lack of physical exercise and low-calcium diet were significantly
      associated with low BMD. Conclusion: Our study showed that there is a high
      prevalence of Vitamin D deficiency and Osteoporosis even in adult women who live
      in a slum area. The findings from the study also suggest the need for large
      community-based studies so that high-risk population can be picked up early and
      early interventions and other lifestyle changes can be instituted so that no
      delay in implementing state and national or international health policy to tackle
      this increasing global health problem. The public awareness is important, and
      strategies to identify and manage low BMD in the primary care setting needs to be
      established and implemented.

PMID- 30294183
TI  - Evaluation of Cardiovascular Risk in Climacteric Women: A Cross-Sectional Study.
AB  - Purpose: To identify cardiovascular risk factors in women between 40 and 65 years
      old in two private clinic of gynecology in Minas Gerais. Methods: Cross-sectional
      study from January/2016 to January/2017 in 137 climacteric women. A standardized
      questionnaire was used to evaluate socio-demographic characteristics, climacteric
      phases, cardiovascular risk factors, menopause (age, time and type), number of
      pregnancies, normal births, abortions, partners and hormonal therapy. The
      evaluation model was used according to the Framingham risk score. Results: The
      median age was 47 years, and 35% were postmenopausal. The majority were married
      and 42.3% caucasian. Abdominal circumference greater than 80 cm was observed in
      87.6%, and greater than 88 cm in 67.2%. High total cholesterol (TC) was observed
      in 48.2%. Low levels of high-density lipoprotein (HDL-c) were observed in 42.3%.
      Elevated levels were observed for low density lipoprotein (LDL-c) in 39.4%,
      triglycerides in 29.9%, and fasting glucose in 8.8%. Also, systolic and diastolic
      blood pressure were considered high in 25.5% cases. Postmenopausal women
      presented higher values of TC and HDL-c. Analysis of the Framingham risk score
      revealed a higher cardiovascular risk for postmenopausal women. Higher values of
      waist circumference, glycemia and triglycerides were observed for women with
      higher cardiovascular risk. Conclusions: Postmenopausal women had a higher risk
      of cardiovascular events when compared to premenopausal ones.

PMID- 30294184
TI  - Study on Prevalence and Severity of Urogenital Complaints in Postmenopausal Women
      at a Tertiary Care Hospital.
AB  - Objective: The objective of this study was (1) to find the prevalence of
      urogenital (UG) complaints after menopause, (2) to evaluate the various risk
      factors for UG problems in postmenopausal women, and (3) to assess the severity
      of the symptoms depending on the duration of menopause. Materials and Methods:
      This study is a prospective study conducted at the Specialty Outpatient
      Department in Safdarjung Hospital over a period of 1 year. Two hundred
      postmenopausal women during this period were screened for UG complaints by
      eliciting detailed history in a pro forma and were divided into two groups based
      on the duration of menopause. Women with preexisting complaints before menopause
      and those with some medical disorders such as diabetes, stroke, or neurological
      problems were excluded from the study. Data were analyzed by standard statistical
      analytical tests. Results: The prevalence of UG symptoms in our study was 67%.
      Group A constitutes 127 (63.5%) participants in which menopause attained was of 1
      5-year duration. Group B comprises the women with >5-year duration of menopause
      and it includes 73 (36.5%) patients. Among the genital complaints, vaginal
      dryness was the most common complaint in both the groups (Group A: 62% and Group
      B: 48%) followed by vaginal discharge or infection (Group A: 28% and Group B:
      25%). Around 19 (15%) in Group A and 10 (13.6%) in Group B were having burning
      micturition (dysuria), the most common complaint encountered. The UG complaints
      were not statistically significantly different in both the groups. The severity
      of the symptoms was significantly different in two groups with more severe
      complaints in Group A as compared to Group B. Conclusion: UG complaints
      associated with estrogen loss can occur episodically throughout a women's life,
      but it is most common and chronic in the duration in postmenopausal women.

PMID- 30294185
TI  - A Prospective, Randomized, Open-Label Study Comparing the Efficacy and Safety of
      Clonazepam versus Nortriptyline on Quality of Life in 40+ Years old Women
      Presenting with Restless Leg Syndrome.
AB  - Introduction: Restless legs syndrome (RLS) is a neurological disorder
      characterized by an urge to move the legs usually accompanied by unpleasant leg
      sensations. RLS also impacts health related quality of life (QOL) in patients
      suffering from it. Further, it affects women more than men. Although a voluminous
      literature of studies is available evaluating the role of benzodiazepines
      (clonazepam and antidepressant (nortriptyline) in the treatment of RLS, but to
      the best of our knowledge, no comparative study is available comparing both of
      these drugs for efficacy and safety for the treatment of RLS QoL among 40 + years
      old women. Materials and Methods: A prospective, randomized, open label
      comparative study was conducted in Postgraduate Department of Pharmacology in
      collaboration with the Department of General Medicine, Government Medical
      College, Jammu, a tertiary care teaching hospital for 1 year. Conclusion:
      Clonazepam proved to be significantly better in improving RLSQoL score.
      Difference between respective baselines of both groups was statistically
      insignificant.

PMID- 30294186
TI  - Diagnostic Utility of Endometrial Aspiration Cytology in Women with Abnormal
      Uterine Bleeding.
AB  - Context: Abnormal uterine bleeding (AUB) is a common problem for which women seek
      gynecological consultation. Endometrial aspiration cytology (EAC) has emerged as
      a minimally invasive and cost-effective diagnostic procedure for screening the
      endometrial status of these patients that can aid in diagnosis in high-burden and
      resource-limited settings. Aims: The study was conducted to evaluate the utility
      of EAC in women with AUB, and the cytological diagnosis was compared with the
      histopathology. Materials and Methods: A total of 100 patients presenting with
      AUB were subjected to EAC using a 4-mm Karman's cannula. Later, they also
      underwent endometrial dilation and curettage. The cytology smears were evaluated
      for architectural and cytomorphological features. The cytological diagnoses
      henceforth made were compared with the histopathological diagnosis to calculate
      sensitivity, specificity, and diagnostic accuracy of EAC. Results: EAC showed a
      sample adequacy of 89% viz a viz 90% for histopathology. EAC showed a sensitivity
      of 87.5% and 100% for diagnosing benign and malignant conditions, respectively.
      There was a good overall agreement between cytological and histopathological
      diagnosis (kappa = 0.585). Conclusions: EAC is an effective and minimally
      invasive procedure for the primary investigation of women with AUB.

PMID- 30294187
TI  - Knowledge and Attitude of Adolescent Girls and Their Mothers Regarding Cervical
      Cancer: A Community-Based Cross-Sectional Study.
AB  - Background: Cervical cancer is the second most commonly diagnosed cancer in
      India. The mother's awareness about the symptoms and risk factors has a large
      impact on the daughter's knowledge and attitude. Mother and adolescent daughter
      duos were selected as the sample as they are the target population at risk for
      suffering from carcinoma cervix. Mothers are the prime information providers and
      in an excellent position to aware their adolescent daughters about cervical
      cancer. Objectives: The aim of this study is to determine knowledge and attitude
      of adolescent girls and their mothers regarding cervical cancer and to find the
      association between the education of the mothers and their knowledge about risk
      factors. Materials and Methods: A community-based cross-sectional study was
      conducted among 100 duos of adolescent daughters along with their mothers
      residing in Balmiki Basti (Delhi), using a predesigned, pretested, semi
      structured interview schedule. The collected data were analyzed using SPSS-22
      version. Results: Only 61% of mothers and 52% of daughters have heard about
      cervical cancer. Inter-menstrual bleeding was the most common symptom recognized
      by the mother (50%) and daughter (44%) duos followed by postmenopausal bleeding
      (47% of mothers and 33% of daughters). Most common risk factors recognized by
      mothers and their daughters were promiscuity and tobacco and smoking. About 81%
      of mothers and 68% of daughters have a positive attitude toward internal
      examination by a gynecologist at least once in 3 years. Human papillomavirus
      infection was recognized as a risk factor by 13 among which 8 were educated till
      graduation (P < 0.05). Conclusions: Study revealed a low-level knowledge about
      cervical cancer among adolescent daughters and their mothers. Therefore, there is
      an urgent need to empower the women by educating them on this issue. Furthermore,
      there is a need to encourage the mothers to communicate the right information to
      their adolescent daughters.

PMID- 30294188
TI  - An Overview of Menopausal Symptoms Using the Menopause Rating Scale in a Tertiary
      Care Center.
AB  - Context: Due to increased life expectancy worldwide, women are expected to spend
      a significant portion of their lives in menopause. Proven prevention strategies
      against serious risks and tested effective treatments for common symptoms may
      remain unutilized in our population if these women are not asked about these
      symptoms. Aim: This study aims to assess the prevalence of different menopausal
      symptoms and their severity according to menopause rating scale (MRS) in women.
      Setting and Design: The present study was a cross-sectional survey, conducted in
      the outpatient department of gynecology and obstetrics. Subjects and Methods:
      After written and informed consent, 121 women having their last menstrual period
      at least 1 year ago were included. The menopausal symptoms were assessed using
      the MRS. The primary outcome measure in this study was the prevalence of
      menopausal symptoms in these women according to MRS and the severity of these
      symptoms. Statistical Analysis Used: Data were analyzed using the SPSS software
      program, version 15.0 (IBM, Armonk, New York, USA). Results: The most common
      symptom was mental and physical exhaustion which was reported by 88 (72%) women,
      followed by joint and muscular discomfort which was reported by 83 (68.59%). Hot
      flushes were reported by 54 (44.62%) respondents. Majority of women reported mild
      to-moderate symptoms. Conclusions: The prevalence of menopausal symptoms is high,
      and a health policy needs to be generated for the region.

PMID- 30294189
TI  - Patterns of Age- and Sex-Related Variations in Bone Mineral Density of Lumbar
      Spine and Total Femur: A Retrospective Diagnostic Laboratory-Based Study.
AB  - Background: Osteoporosis is a major public health problem and should be a
      priority for healthcare providers and policymakers as it is an important reason
      of morbidity, mortality, and high-cost incurred in the management of its
      complications such as hip fractures. This study is designed to assess the bone
      mineral density (BMD) variation with age, site, and sex. Study is based on
      diagnostic laboratory data of BMD. Methods: A retrospective analysis was
      conducted on a sample population of 935 persons (73.5% women, 26.4% men), who
      underwent dual-energy X-ray absorptiometry scan between 2015 and 2017 in a
      National Accreditation Board for Testing and Calibration Laboratories accredited
      Mumbai (Maharashtra, India) based diagnostic laboratory. Lumbar spine, right and
      left total femur, BMD were analyzed across age, sex, and sites. The prevalence of
      low BMD and osteoporosis at these sites has been estimated as per the World
      Health Organization criteria of osteoporosis diagnosis using T scores. Results:
      Overall the prevalence of osteoporosis was found to be 6.4%, 5.5%, and 16.4%,
      while the prevalence of low BMD was 32.6%, 32.8%, and 31.2% at right total femur,
      left total femur, and lumbar spine, respectively. The decline in BMD at lumbar
      spine is more among women and it was a consistent decline with age, while among
      men' decline rate was less at all three sites. Conclusion: Our study highlighted
      the variation of BMD at different sites of body and higher vulnerability of spine
      for fragility fractures. Our study has shown a sharp decline in BMD among women
      during transition from 5th to 6th decade which signifies association of menopause
      with osteoporosis. Major limitation of the study is unavailability of clinical
      profiles of the subjects because of which it is difficult to ascertain whether
      BMD estimation was a diagnostic or screening procedure. In addition, study is
      conducted in diagnostic lab settings, due to which it is possible to overestimate
      prevalence of low BMD and osteoporosis by extrapolating these findings to the
      community.

PMID- 30294190
TI  - Retained Fetal Bones: An Unusual Cause of Granulomatous Reaction on Papanicolaou
      Smear.
AB  - Granulomas are a rare finding on Papanicolaou (Pap) smear which if encountered
      are usually attributed to tuberculosis, especially in an endemic country like
      India. Here, we report an interesting case of a 40-year-old female presenting
      with blood-stained discharge and chronic pelvic pain for 8 years. She was advised
      Pap smear which showed granulomatous inflammation suggestive of tuberculosis. The
      patient was worked up for tuberculosis which was noncontributory. Dilatation and
      curettage was done which revealed multiple small bones and bony chips in the
      endometrial cavity. Following the removal of bones, the patient showed
      considerable symptomatic improvement. Repeat Pap smear did not reveal any
      evidence of granuloma. Even after extensive search of literature, we did not come
      across any such case report in which intrauterine retention of fetal bones evoked
      a granulomatous response in cervical smears though the presence of uterine
      granulomas in response to foreign body has been well documented.

PMID- 30294191
TI  - Low-Grade Endometrial Stromal Sarcoma in a Postmenopausal Woman with Third-Degree
      Uterovaginal Prolapse: A Rare Case with Review of the Literature.
AB  - Endometrial stromal sarcomas (ESSs) are rare malignant tumors of the uterus that
      arise from the endometrial stroma, the annual incidence of ESS being 1-2/million
      women. Patients present with nonspecific complaints of abnormal uterine bleeding,
      pelvic pain, and pressure symptoms. Postmenopausal women rarely present with a
      low-grade ESS, as it is more common in younger women. ESS is usually confused
      with leiomyomas radiologically. Histopathological examination and
      immunohistochemistry are essential for the diagnosis. We, herein, report a case
      of a postmenopausal female who presented with something coming out per vagina.
      The clinical impression was that of a third-degree uterovaginal prolapse that on
      histopathological examination was diagnosed as a low-grade ESS.

PMID- 30294192
TI  - Asymptotic Behavior of Cox's Partial Likelihood and its Application to Variable
      Selection.
AB  - For theoretical properties of variable selection procedures for Cox's model, we
      study the asymptotic behavior of partial likelihood for the Cox model. We find
      that the partial likelihood does not behave like an ordinary likelihood, whose
      sample average typically tends to its expected value, a finite number, in
      probability. Under some mild conditions, we prove that the sample average of
      partial likelihood tends to infinity at the rate of the logarithm of the sample
      size, in probability. We apply the asymptotic results on the partial likelihood
      to study tuning parameter selection for penalized partial likelihood. We find
      that the penalized partial likelihood with the generalized cross-validation (GCV)
      tuning parameter proposed in Fan and Li (2002) enjoys the model selection
      consistency property, despite the fact that GCV, AIC and Cp , equivalent in the
      context of linear regression models, are not model selection consistent. Our
      empirical studies via Monte Carlo simulation and a data example confirm our
      theoretical findings.

PMID- 30294193
TI  - Activity evaluation of some psychoactive drugs with the application of QSAR/QSPR
      modeling methods.
AB  - A set of psychoactive drugs has been analyzed with the use of quantitative
      structure-activity/property relationships methods. The purpose of this study was
      to demonstrate both the common and differentiating characteristics of the above
      mentioned chemical compounds, physicochemical as well as pharmacological based on
      the quantum chemical calculations and selected biological activity data and
      chromatographic retention parameters. During the study, the ab initio model of
      molecular modeling was performed and PCA, FA, and MLR as the types of chemometric
      approach. QSAR/QSPR models were proposed based on chosen statistically
      significant descriptors. The relationship between the structure and biological
      activity data was able to class and describe the psychoactive properties of the
      molecules studied. The applied chemometric approaches revealed the influential
      features of tested structures responsible for their pharmacological activity
      together with some additional physicochemical properties.

PMID- 30294194
TI  - Family Matters: The Nurse's Role in Assessing Family Health History in Ocular
      Disease.

PMID- 30294195
TI  - Cost Effectiveness of Strategies for Recruiting Low-Income Families for
      Behavioral Parent Training.
AB  - The goal of this study was to assess cost, effectiveness, and cost-effectiveness
      of recruitment strategies used to engage low-income families of young children
      with disruptive behavior disorder to participate in a Behavioral Parent Training
      (BPT) program. For this analysis, we used data on labor and non-labor resources
      associated with 13 recruitment strategies implemented in February 2014 through
      February 2016. We assessed the effectiveness of each strategy as the number of
      families that enrolled into the study. Cost-effectiveness of each recruitment
      strategy was expressed as cost per family enrolled; analysis was conducted in
      2016. We calculated the cost of total recruitment effort for 13 strategies during
      the 2-year period to be $11,496 with an average cost of $885 per recruitment
      strategy or $255 per enrolled family. Across strategies, total costs ranged from
      $25 to $2,540. "University mass e-mail" and "school flyers" resulted in the most
      phone screens (34 each); however, only 10% of these families enrolled in the
      study (3 and 4 families, respectively). "Craigslist" was the most effective
      strategy with 30 families screened and 11 of them enrolling. Three strategies did
      not yield any participants. The four strategies with the lowest cost per family
      enrolled were "Facebook page," "Craigslist," "university mass e-mail," and
      "organization/agency" (< $90). In conclusion, we found that some recruitment
      strategies were more successful at engaging low-income families to participate in
      a BPT program than others. Our results indicate that using a combination of
      recruitment strategies may be the optimal approach for recruiting low-income
      families.

PMID- 30294196
TI  - Change in Maternal Stress for Families in Treatment for their Children with
      Oppositional Defiant Disorder.
AB  - Our objective was to predict change in maternal stress over the course of a
      randomized clinical trial comparing the efficacy of two interventions for
      Oppositional Defiant Disorder (ODD): Parent Management Training and Collaborative
      & Proactive Solutions. In a secondary analysis of data collected from this
      randomized clinical trial, we examined whether children's self-reported positive
      relations with their parents impacted responsiveness to treatment, which in turn
      impacted maternal stress. One hundred thirty-four children and their parents
      (38.1% female, ages 7-14, M age = 9.51, SD = 1.77) were tracked across three time
      points: pre-treatment; one-week post-treatment; and six-month post-treatment.
      Hierarchical linear models tested change in children's reports of positive
      relations with parents, clinician reports of ODD severity, and maternal reports
      of parenting stress. Models then tested multilevel mediation from positive
      relations with parents, through ODD severity, onto maternal stress. Hypothesized
      indirect effects were supported such that children's reports of positive views
      toward parents uniquely predicted reductions in ODD severity over time, which in
      turn uniquely predicted reductions in maternal stress. Results highlight the
      promise of potential secondary benefits for parents following interventions for
      children with oppositional problems. Furthermore, results underscore the
      importance of the parent-child relationship as both a protective factor and as an
      additional target to complement interventions for child disruptive behaviors.

PMID- 30294197
TI  - When the Alpha is the Omega: P-Values, "Substantial Evidence," and the 0.05
      Standard at FDA.
AB  - A prominent feature of statistical reasoning for nearly a century, the p-value
      plays an especially vital role in the clinical testing of new drugs. Over the
      last fifty years, the U.S. Food and Drug Administration (FDA) has relied on p
      values and significance testing to demonstrate the efficacy of new drugs in the
      premarket approval process. This article seeks to illuminate the history of this
      statistic and explain how the statistical significance threshold of 0.05,
      commonly decried as an arbitrary cutoff, is a useful tool that came to be the
      cornerstone of FDA decision-making.

PMID- 30294198
TI  - Sarcoidosis-associated Pulmonary Hypertension: Pathophysiology, Diagnosis, and
      Treatment.
AB  - Clinicians in pulmonary medicine frequently confront the challenge of screening,
      diagnosis and management of pulmonary hypertension (PH) in sarcoidosis patients
      who present with unexplained dyspnea. Sarcoidosis associated pulmonary
      hypertension (SAPH) is most prevalent in patients with pulmonary fibrosis, though
      it can be independent of airflow obstruction or restriction. SAPH independently
      associates with significantly increased mortality and decreased functional
      capacity, outcomes which can be mitigated by early detection and focused
      treatment. In this review, we discuss the pathophysiology of SAPH, which may
      resemble pulmonary arterial hypertension as well as secondary causes of PH. We
      offer a screening algorithm for SAPH, and advocate for detailed assessment of the
      cause of PH in each patient prior to choice of an individualized treatment plan.
      We note that treatment of sarcoidosis via immune suppression is typically
      insufficient to adequately treat SAPH. We discuss secondary causes of SAPH such
      as left heart disease, sleep disordered breathing, and thromboembolic disease,
      and the evidence for use of PH-specific therapy in select cases of SAPH.
      Management of SAPH by clinicians experienced in PH, with early referral to
      transplantation in refractory cases is advised.

PMID- 30294199
TI  - Field Investigation of Ambulatory Clinic Exam Room Design with respect to
      Computing Devices: A Pilot Study.
AB  - The Department of Veterans Affairs (VA) has developed a new exam room design
      standard that is intended to facilitate a greater degree of patient centeredness.
      This new design includes a wall-mounted monitor on an armature system and a
      moveable table workspace. To date, however, this design has not been formally
      evaluated in a field setting. We conducted observations and interviews with
      primary care providers and their patients from three locations within the Phoenix
      VA Health Care System, in a pilot study comparing the new exam room design
      standard with the older legacy exam rooms. When using the new exam room layout,
      providers spent a greater proportion of time focused on the patient, spent more
      time in screen-sharing activities with the patient, and had a higher degree of
      self-reported situation awareness. However, the legacy exam rooms were perceived
      as better facilitating workflow integration. Provider and patient debrief
      interviews were supportive of the new exam room design. Overall, our field study
      results suggest that the new exam room design does contribute to a greater degree
      of patient centeredness, though more thorough evaluations are required to support
      these preliminary results.

PMID- 30294200
TI  - Adversity and children experiencing family homelessness: Implications for health.
AB  - This study tests links between adversity and health problems among children in
      family emergency housing. Children who experience family homelessness are at risk
      to also experience high levels of stress, health problems, and need for pediatric
      care. Understanding the connection between stress and health holds the potential
      to reduce persistent health disparities. Analyses tested whether experiencing a
      greater number of stressful life events during the early years of life was
      related to worse health conditions, emergency health care utilization, and
      hospitalizations. Parents noted children's experience of negative stressful life
      events, health problems, emergency room (ER) use, and hospitalization. Two
      cohorts of kindergarten-aged children staying in emergency family housing
      participated in the study in 2006-07 (n = 104) and in 2008-09 (n = 138), with the
      results examined separately. In both cohorts, more health problems were
      acknowledged for children exposed to more negative stressful life events.
      Stressful life events were not related to ER use but did relate to
      hospitalization for the 2006-07 cohort. Results affirm links between stress in
      early childhood and health problems among children living in emergency housing.
      Findings are consistent with the hypothesis that adversity in early childhood
      contributes to income and racial disparities in health.

PMID- 30294201
TI  - Bilberry extract and anthocyanins suppress unfolded protein response induced by
      exposure to blue LED light of cells in photoreceptor cell line.
AB  - Purpose: The purpose of this study was to investigate the effects of bilberry
      extract with its anthocyanins on retinal photoreceptor cell damage and on the
      endoplasmic reticulum (ER) stress induced by exposure to blue light-emitting
      diode (LED) light. Methods: Cultured murine photoreceptor cells (661W) were
      exposed to blue LED light with or without bilberry extract or its anthocyanins in
      the culture media. Aggregated short-wavelength opsin (S-opsin) in murine
      photoreceptor cells was observed with immunostaining. The expression of factors
      involved in the unfolded protein response was examined with immunoblot analysis
      and quantitative real-time reverse transcription (RT)-PCR. Furthermore, cell
      death was observed with double staining with Hoechst 33342 and propidium iodide
      after dithiothreitol (DTT) treatment. Results: Bilberry extract and anthocyanins
      suppressed the aggregation of S-opsin, activation of ATF4, and expression of the
      mRNA of the factors associated with the unfolded protein response (UPR). In
      addition, bilberry extract and the anthocyanins inhibited the death of
      photoreceptor cells induced by DTT, an ER stress inducer. Conclusions: These
      findings suggest that bilberry extract containing anthocyanins can alter the
      effects of blue LED light and DTT-induced retinal photoreceptor cell damage.
      These effects were achieved by modulating the activation of ATF4 and through the
      suppression of the abnormal aggregation of S-opsin.

PMID- 30294203
TI  - DETENTION OUTLET RETROFIT IMPROVES THE FUNCTIONALITY OF EXISTING DETENTION BASINS
      BY REDUCING EROSIVE FLOWS IN RECEIVING CHANNELS.
AB  - By discharging excess stormwater at rates that more frequently exceed the
      critical flow for stream erosion, conventional detention basins often contribute
      to increased channel instability in urban and suburban systems that can be
      detrimental to aquatic habitat and water quality, as well as adjacent property
      and infrastructure. However, these ubiquitous assets, valued at approximately
      $600,000 per km2 in a representative suburban watershed, are ideal candidates to
      aid in reversing such cycles of channel degradation because improving their
      functionality would not necessarily require property acquisition or heavy
      construction. The objective of this research was to develop a simple, cost
      effective device that could be installed in detention basin outlets to reduce the
      erosive power of the relatively frequent storm events (~ < two-year recurrence)
      and provide a passive bypass to maintain flood control performance during
      infrequent storms (such as the 100-year recurrence). Results from a pilot
      installation show that the Detain H2O device reduced the cumulative sediment
      transport capacity of the preretrofit condition by greater than 40%, and
      contributed to reduced flashiness and prolonged baseflows in receiving streams.
      When scaling the strategy across a watershed, these results suggest that
      potential gains in water quality and stream channel stability could be achieved
      at costs that are orders of magnitude less than comparable benefits from newly
      constructed stormwater control measures.

PMID- 30294202
TI  - Effects of aging and environmental tobacco smoke exposure on ocular and plasma
      circulatory microRNAs in the Rhesus macaque.
AB  - Purpose: To identify changes induced by environmental tobacco smoke (ETS) in
      circulatory microRNA (miRNA) in plasma and ocular fluids of the Rhesus macaque
      and compare these changes to normal age-related changes. Tobacco smoke has been
      identified as the leading environmental risk factor for age-related macular
      degeneration (AMD). Methods: All Rhesus macaques were housed at the California
      National Primate Research Center (CNPRC), University of California, Davis. Four
      groups of animals were used: Group 1 (1-3 years old), Group 2 (19-28 years old),
      Group 3 (10-16 years old), and Group 4 (middle aged, 9-14 years old). Group 4 was
      exposed to smoke for 1 month. Ocular fluids and plasma samples were collected,
      miRNAs isolated, and expression data obtained using Affymetrix miRNA GeneTitan
      Array Plates 4.0. Bioinformatics analysis was done on the Affymetrix Expression
      Console (EC), Transcriptome Analysis Software (TAS) using ANOVA for candidate
      miRNA selection, followed by Ingenuity Pathway Analysis (IPA). Results: The
      expression of circulatory miRNAs showed statistically significant changes with
      age and ETS. In the plasma samples, 45 miRNAs were strongly upregulated (fold
      change >+/-1.5, p<0.05) upon ETS exposure. In the vitreous, three miRNAs were
      statistically significantly downregulated with ETS, and two of them (miR-6794 and
      miR-6790) were also statistically significantly downregulated with age. Some
      retinal layers exhibited a thinning trend measured with optical coherence
      tomography (OCT) imaging. The pathways activated were IL-17A, VEGF, and
      recruitment of eosinophils, Th2 lymphocytes, and macrophages. Conclusions: ETS
      exposure of Rhesus macaques resulted in statistically significant changes in the
      expression of the circulatory miRNAs, distinct from those affected by aging. The
      pathways activated appear to be common for ETS and AMD pathogenesis. These data
      will be used to develop an animal model of early dry AMD.

PMID- 30294204
TI  - Serum insulin-like growth factor 1 (IGF-1) in multiple sclerosis: relation to
      cognitive impairment and fatigue.
AB  - Background: Multiple sclerosis (MS) is a chronic demyelinating central nervous
      system (CNS) disease. Changes in insulin growth factor 1 (IGF-1) input to the
      brain can affect survival of myelin and CNS cells. The study aims to investigate
      the relation of serum IGF-1 levels with cognitive impairment and fatigue in MS
      patients. Methods: This study was conducted on 46 MS patients and 46 healthy
      controls. All participants were subjected to clinical assessment, serum IGF-1
      levels, expanded disability status scale (EDSS), modified fatigue impact scale
      (MFIS), and Montreal cognitive assessment (MoCA) scale. Results: There was no
      significant difference between patients and controls regarding serum IGF-1 levels
      (P = 0.19). However, low serum levels of IGF-1 have significantly greater odds
      for fatigue (P = 0.002) and cognitive impairment (P < 0.001). Also, serum IGF-1
      levels have a significant negative correlation with MFIS (r = - 0.701 and P <
      0.001) and a significant positive correlation with MoCA scale (r = + 0.84 and P <
      0.001). Conclusions: The results, specifically that low levels of serum IGF-1 was
      associated with cognitive impairment and fatigue in MS, suggest that IGF-I may be
      involved in the pathogenesis of cognitive deficits and fatigue in MS disease.

PMID- 30294206
TI  - A review of the family Trichopolydesmidae in North Africa with a description of a
      new species from Tunisia.
AB  - A new species of the genus Haplocookia Brolemann, 1915 is described from Cap Bon
      Peninsula in Tunisia (North Africa) and a historical account of the poorly
      understood genera Haplocookia and Heterocookia Silvestri, 1898 is provided.
      Comments on the taxonomy of the family Trichopolydesmidae are presented, as well
      as an identification key to the trichopolydesmid species hitherto known from
      North Africa and an updated list of the Polydesmida in the region.

PMID- 30294205
TI  - The relationship between the severity of disability and serum IL-8 in acute
      ischemic stroke patients.
AB  - Background: Stroke is the third leading cause of death and leading cause of adult
      disability worldwide. Long-term disability is a significant problem among
      survivors; post-stroke inflammation is well known to contribute to the expansion
      of the ischemic lesion resulting in significant morbidity and disability. To
      study the impact of serum level of IL-8 on severity of disability in patients
      with acute ischemic stroke in the first 48 h post stroke. Methods: A cross
      sectional case control study was conducted on 44 patients with acute ischemic
      stroke (in the first 48 h). The patients were subjected to full neurological
      examination, computed tomography (CT) and magnetic resonance imaging (MRI) of the
      brain, and assessment of stroke disability using the National Institute of Health
      Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Measurement of the serum
      levels of IL-8, erythrocyte sedimentation rate, and C-reactive protein (CRP) was
      done. Forty-four matched control subjects for their age and sex were included for
      comparison of serum level of IL-8. Results: The level of IL-8 was significantly
      higher in the patients than in the control subjects (p < 0.001).There was a
      statistically significant positive correlation between serum level of IL-8 and
      disability assessed by NIHSS (r = 0.42, p = 0.004). The patients with moderate
      disability showed significant higher IL-8 levels than those with minor disability
      (p = 0.02). Conclusion: The severity of disability in early acute ischemic stroke
      is highly correlated to the serum level of IL-8.

PMID- 30294207
TI  - Additions to the leafhopper genus Mimotettix (Hemiptera, Cicadellidae,
      Deltocephalinae) from Yunnan Province, China.
AB  - Two new leafhopper species: Mimotettixmultispinosus sp. n. and M.sinuatus sp. n.
      are described and illustrated from Yunnan, China. A checklist to the species of
      Mimotettix from Yunnan and a key to species from the region are also provided.

PMID- 30294208
TI  - Evaluation of the population dynamics of microalgae isolated from the state of
      Chiapas, Mexico with respect to the nutritional quality of water.
AB  - As Chiapas state, Mexico, counts on an extensive hydrography with diverse
      nutrimental and climatic characteristics, it therefore allows isolating and
      identifying microalgae with bioenergetics potential. For this purpose, samples
      from 8 locations were collected, corresponding to 6 rivers, a wastewater and a
      springwater. The isolation of microalgae was developed for 4 weeks with 12:12
      light/dark cycles. We demonstrated that the most efficient means for the
      isolation of microalgae of the hydrographic areas evaluated was the medium BG11
      with 80.53% effectiveness. Of the microalgal consortium identified, 90% are
      composed of microalgae belonging to the class Chlorophycear. It was shown that
      another factor favouring the richness of morphotypes identified in the Santo
      Domingo River is associated with adequate concentrations of macroelements such as
      nitrates, nitrites, ammonium, phosphorus, sodium, potassium, magnesium and
      calcium at concentrations of 0.03 mg/l, 0.0006 mg/l, 0.08 mg/l, 0.03 mg/l, 62.93
      mg/l, 5.46 mg/l, 34.52 mg/l and 48.78 mg/l respectively and microelements such as
      copper, zinc, iron, andmanganese at concentrations less than 0.2 mg/l in all
      microelements. The identified morphotypes, according to literature, have lipid
      contents ranging from 2 to 90%; this is of biotechnological importance for the
      production of biodiesel.

PMID- 30294209
TI  - Three new species of Krogia (Ramalinaceae, lichenised Ascomycota) from the
      Paleotropics.
AB  - Krogiaborneensis Kistenich & Timdal, K.isidiata Kistenich & Timdal and
      K.macrophylla Kistenich & Timdal are described as new species, the first from
      Borneo and the two latter from New Caledonia. The new species are supported by
      morphology, secondary chemistry and DNA sequence data. Krogiaborneensis and
      K.isidiata contain sekikaic and homosekikaic acid, both compounds reported here
      for the first time from the genus. Krogiamacrophylla contains an unknown compound
      apparently related to boninic acid as the major compound. DNA sequences (mtSSU
      and nrITS) are provided for the first time for Krogia and a phylogeny of the
      genus based on 15 accessions of five of the six accepted species is presented.
      Krogiaantillarum is reported as new to Brazil, Guatemala and Mexico.

PMID- 30294211
TI  - Growth dynamics of Dracaena cinnabari under controlled conditions as the most
      effective way to protect endangered species.
AB  - Dracaena cinnabari Balf. fil. is an endangered endemic species growing on the
      Yemeni island of Soqotra. Dracaena woodlands are considered as one of the oldest
      forest communities on Earth. Uncontrolled grazing unfortunately caused a lack of
      naturally occurring regeneration. Our two-year research was focused on the growth
      dynamics of Dracaena seedlings from two separate populations. One hundred of
      germinated seeds from two different altitudes from the island were sown and
      planted under the same conditions. Average increment and difference between the
      growth dynamics of plants from the two localities were investigated. The observed
      data on this plant species revealed very interesting, hitherto unknown results.
      (1) The seedlings germinated within a time period from four to ten weeks.
      Germination rate was 90% on the Firmihin highland plateau and 78% on the Scand
      Mountain. (2) Average plant length from both localities was almost the same (24.9
      cm) at the end of measurement. Differences in values between the two populations
      proved as non-significant. (3) A significant difference was found in the number
      of leaves and in the sum of lengths of all leaves on one plant. While the
      seedlings from Firmihin featured a wide spreading above-ground part with a large
      number of leaves, the plants from Scand invested more energy into faster leaves
      elongation rate. (4) Growth dynamics reflected seasonal changes. Increments were
      slower or ceased during the period of vegetative rest from autumn to spring. (5)
      Average mortality rate was 13%. Most of the plants died during the period of
      vegetative rest. Further study on germination and regeneration under artificial
      conditions seems like the only way to prevent species extinction.

PMID- 30294210
TI  - Morphological characteristics of worm lizard, Diplometopon zarudnyi (Squamata:
      Trogonophidae), in the central region of Saudi Arabia.
AB  - We report morphometric data for 133 specimens of Diplometopon zarudnyi (Squamata:
      Trogonophidae) collected across its range within Riyadh province of Saudi Arabia.
      One-way analyses of variance revealed that differences exist in most characters.
      Snout-vent length and vent-tail length showed slight and inconsistent differences
      among samples. D. zarudnyi is characterized by 164-175 body annuli; 165-178
      dorsal annuli; 13-17 caudal annuli with absence of caudal autotomy. In addition,
      2-4 lateral annuli; 45-54 mid-body segments; 39-50 posterior segments; 4-5 head's
      plates and 4-6 pre-cloacal pores were recorded in both males and females without
      gender difference. The present study revealed the widespread distribution of this
      species in the studied region, since land topography in this area is
      characterized by the absence of any natural barriers which could restrict the
      spread of this amphisbaenian lizard D. zarudnyi.

PMID- 30294212
TI  - Effect of gastric and small intestinal digestion on lactic acid bacteria activity
      in a GIS1 simulator.
AB  - The selection of probiotic strains resistant to gastrointestinal transit is an
      important stage when developing supplements that contain viable biomass. A total
      of six strains belonging to different genotypes were tested and compared with
      both a positive and negative control (Lactobacillus plantarum 5s). Significant
      differences were found between strains as a result of gastrointestinal transit
      using the in vitro GIS1 static simulator. The Lactobacillus rhamnosus 428ST
      strain showed maximum viability as a result of in vitro transit, featuring a
      survival capacity value, Cs, of over 50 +/- 0.01%. The remaining genotypes that
      were tested showed significant reductions in the enzymes and bile salts at the
      time of action. The value of the survivability capacity was directly correlated
      with the synthesis of exopolysaccharides and lactic acid. The test results of the
      GIS1 system have been compared with those of other studies on gastrointestinal
      transit resistance that used dynamic models.

PMID- 30294213
TI  - Biological activity of Cymbopogon schoenanthus essential oil.
AB  - Introduction: A number of plant species, including Cymbopogon schoenanthus, are
      traditionally used for the treatment of various diseases. C. schoenanthus is
      currently, traded in the Saudi markets, and thought to have medicinal value. This
      study aimed at investigating the biological activities of C. schoenanthus against
      both Gram-positive and Gram-negative bacteria and to identify its chemical
      ingredients. Materials and methods: The inhibitory effects of water extracts of
      C. schoenanthus essential oils were evaluated against ten isolates of both Gram
      positive and Gram-negative bacteria using the agar well diffusion and dilution
      methods. The minimum inhibitory concentration (MIC) was assayed using the Broth
      microdilution test on five of the ten isolates. The death rates were determined
      by the time kill assay, done according to the Clinical Laboratory Standards
      Institute (CLSI) guidelines. The chemical composition of the essential oils of
      the plant was performed using GC/MS. Results: The C. schoenanthus essential oil
      was effective against Escherichia coli, Staphylococcus aureus, methicillin
      sensitive (MSSA) S. aureus (MRSA) and Klebsiella pneumoniae. The essential oil
      was not effective against Staphylococcus saprophyticus at the highest
      concentration applied of >150 MUg/ml. The MIC values were as follows: 9.37 MUg/ml
      for E. coli 4.69 MUg/ml for S. aureus (MRSA), 2.34 mg/ml for MSSA and 2.34 MUg/ml
      for K. pneumoniae. The time-kill assay indicated that there was a sharp time
      dependent decline in K. pneumoniae counts in the presence of the oil. This is in
      contrast to a gradual decline in the case of S. aureus under the same conditions.
      The eight major components of the essential oil were: piperitone (14.6%),
      cyclohexanemethanol (11.6%), beta-elemene (11.6%), alpha-eudesmol (11.5%), elemol
      (10.8%), beta-eudesmol (8.5%), 2-naphthalenemethanol (7.1%) and gamma-eudesmol
      (4.2%). Conclusion: The results of the present study provide a scientific
      validation for the traditional use of C. schoenanthus as an antibacterial agent.
      Future work is needed to investigate and explore its application in the
      environmental and medical fields. In addition, to evaluating the efficacy of the
      individual ingredients separately to better understand the underlying mechanism.

PMID- 30294215
TI  - Spatial and seasonal variations in the biofunctional lipid substances
      (fucoxanthin and fucosterol) of the laboratory-grown edible Japanese seaweed
      (Sargassum horneri Turner) cultured in the open sea.
AB  - This work studied the effect of spatial and seasonal differences on the
      accumulation of functional lipid components in Sargassum horneri (Turner), an
      edible Japanese seaweed popularly called Akamoku. S. horneri obtained from
      Samenoura bay area of Japan was laboratory cultured to evaluate the effect of
      temperature on the accumulation of total lipids (TL), fucoxanthin (Fx) and
      fucosterol (Fs) by the alga. The laboratory cultured 3 month old S. horneri were
      cultured in the open sea in two different geographical locations off Usujiri and
      Matsushima to evaluate the monthly variations, over a year, in their TL, Fx and
      Fs contents. S. horneri grown off the Usujiri area accumulated the maximum TL
      close to 193 mg g-1 dry weight during the coldest part of the year. Fx and Fs
      contributed 5.6% and 16.2% of the TL in S. horneri harvested off Usujiri in
      February. Further, in spite of being the same species and parent stock, S.
      horneri grown off the Matsushima area accumulated less TL, Fx and Fs as compared
      to their Usujiri counterparts. Our study clearly indicates the role of
      temperature and light apart from nutritional profile and depth of waters where
      the seaweed was grown on the accumulation of functional lipid components in S.
      horneri.

PMID- 30294214
TI  - Optimization of conditions to extract high quality DNA for PCR analysis from
      whole blood using SDS-proteinase K method.
AB  - In case of studies associated with human genetics, genomics, and pharmacogenetics
      the genomic DNA is extracted from the buccal cells, whole blood etc. Several
      methods are exploited by the researchers to extract DNA from the whole blood. One
      of these methods, which utilizes cell lysis and proteolytic properties of sodium
      dodecyl sulfate (SDS) and proteinase K respectively, might also be called SDS-PK
      method. It does not include any hazardous chemicals such as phenol or chloroform
      and is inexpensive. However, several researchers report the same method with
      different formulas and conditions. During our experiments with whole blood DNA
      extraction we experienced problems such as protein contamination, DNA purity and
      yield when followed some SDS-PK protocols reported elsewhere. A260/A280 and
      A260/A230 ratios along with PCR amplification give a clear idea about the
      procedure that was followed to extract the DNA. In an effort to increase the DNA
      purity from human whole blood, we pointed out some steps of the protocol that
      play a crucial role in determining the extraction of high quality DNA.

PMID- 30294216
TI  - Growth inhibitory properties of lactose fatty acid esters.
AB  - Sugar esters are biodegradable, nonionic surfactants which have microbial
      inhibitory properties. The influence of the fatty acid chain length on the
      microbial inhibitory properties of lactose esters was investigated in this study.
      Specifically, lactose monooctanoate (LMO), lactose monodecanoate (LMD), lactose
      monolaurate (LML) and lactose monomyristate (LMM) were synthesized and dissolved
      in both dimethyl sulfoxide (DMSO) and ethanol. Minimum inhibitory concentrations
      (MIC) and minimum bactericidal concentrations (MBC) were determined in growth
      media. LML was the most effective ester, exhibiting MIC values of <0.05 to <5
      mg/ml for each Gram-positive bacteria tested (Bacillus cereus, Mycobacterium KMS,
      Streptococcus suis, Listeria monocytogenes, Enterococcus faecalis, and
      Streptococcus mutans) and MBC values of <3 to <5 mg/ml for B. cereus, M. KMS, S.
      suis, and L. monocytogenes. LMD showed MIC and MBC values of <1 to <5 mg/ml for
      B. cereus, M. KMS, S. suis, L. monocytogenes, and E. faecalis, with greater
      inhibition when dissolved in ethanol. LMM showed MIC and MBC values of <1 to <5
      mg/ml for B. cereus, M. KMS, and S. suis. LMO was the least effective showing a
      MBC value of <5 mg/ml for only B. cereus, though MIC values for S. suis and L.
      monocytogenes were observed when dissolved in DMSO. B. cereus and S. suis were
      the most susceptible to the lactose esters tested, while S. mutans and E.
      faecalis were the most resilient and no esters were effective on Escherichia coli
      O157:H7. This research showed that lactose esters esterified with decanoic and
      lauric acids exhibited greater microbial inhibitory properties than lactose
      esters of octanoate and myristate against Gram-positive bacteria.

PMID- 30294217
TI  - In vivo fertilizing ability of stallion spermatozoa processed by single layer
      centrifugation with Androcoll-ETM.
AB  - A colloid with a species specific silane-coated, silica-based formulation,
      optimized for stallion (Androcoll-ETM), enables a better sub-population of
      spermatozoa to be selected from stallion ejaculates. However, such a practice has
      not been critically evaluated in stallions with fertility problems. In this study
      we evaluate whether single-layer centrifugation (SLC) through Androcoll-ETM could
      be used to enhance fertility rates in a subfertile stallion. Ejaculates were
      obtained from two different stallions, one Lusitano (fertile) and one Sorraia
      (subfertile), with distinct sperm characteristics and fertility. Motility,
      morphology, plasma membrane structural (eosin-nigrosin) and functional integrity
      (HOS test), mitochondrial functionality (Deltapsim; JC-1) and longevity (motility
      after 72 h cooling) after centrifugation in Androcoll-ETM, as well as pregnancy
      rates obtained after artificial insemination (AI), with and without (control
      group) SLC-treated sperm were assessed. The effect of SLC on sperm
      characteristics, and fertility results were evaluated by ANOVA and Fisher
      procedures, respectively. Our results showed that SLC-selected sperm did not
      differ from the raw semen in terms of viability, morphology, response to hypo
      osmotic conditions (HOS test) and mitochondrial membrane potential (?DeltaPsimit;
      JC-1). Sperm motility in cooled samples was not improved by SLC treatment. Our
      data show that SLC through Androcoll-ETM has no effect on pregnancy rates in the
      stallions used in this trial.

PMID- 30294218
TI  - Expression of variable viruses as herpes simplex glycoprotein D and varicella
      zoster gE glycoprotein using a novel plasmid based expression system in insect
      cell.
AB  - Several prokaryotic and eukaryotic expression systems have been used for in vitro
      production of viruses' proteins. However eukaryotic expression system was always
      the first choice for production of proteins that undergo post-translational
      modification such as glycosylation. Recombinant baculoviruses have been widely
      used as safe vectors to express heterologous genes in the culture of insect
      cells, but the manipulation involved in creating, titrating, and amplifying viral
      stocks make it time consuming and laborious. Therefore, to facilitate rapid
      expression in insect cell, a plasmid based expression system was used to express
      herpes simplex type 1 glycoprotein D (HSV-1 gD) and varicella zoster glycoprotein
      E (VZV gE). Recombinant plasmids were generated, transfected into insect cells
      (SF9), and both glycoproteins were expressed 48 h post-infection. A protein with
      approximately molecular weight of 64-kDa and 98-kDa for HSV-1 gD and VZV gE
      respectively was expressed and confirmed by SDS. Proteins were detected in insect
      cells cytoplasm and outer membrane by immunofluorescence. The antigenicity and
      immunoreactivity of each protein were confirmed by immunoblot and ELISA. Results
      suggest that this system can be an alternative to the traditional baculovirus
      expression for small scale expression system in insect cells.

PMID- 30294219
TI  - Effects of water-deficit stress and paclobutrazol on growth, relative water
      content, electrolyte leakage, proline content and some antioxidant changes in
      Curcuma alismatifolia Gagnep. cv. Chiang Mai Pink.
AB  - Effects of water-deficit stress and paclobutrazol (PBZ) on the physiological and
      biochemical changes in Curcuma alismatifolia Gagnep. cv. Chiang Mai Pink
      (Zingiberaceae) were investigated. One hundred rhizomes were grown for 30-35 days
      and then divided into the following 4 treatments: (1) well-watered, (2) not
      watered, (3) well-watered and treated with 1500 ppm PBZ being applied once to the
      soil, and (4) not watered but treated with 1500 ppm PBZ. After 50 days of growth,
      watering was withheld for 30 days. After water stress was initiated, plant
      height, plant fresh weight, soil water content, relative water content (RWC),
      electrolyte leakage (EL), proline content, vitamin C and E content, as well as
      the activities of catalase (CAT) and superoxide dismutase (SOD) in the leaves
      were determined every 10 days. The results showed that water-deficit stress
      decreased plant height and plant fresh weight, whereas this stress and PBZ did
      not result in a decrease in these parameters. Water stress reduced RWC, but
      induced EL and proline content in the leaves. However, the leaves showed opposite
      results when PBZ was added to the treatments. Some antioxidants such as vitamin
      C, vitamin E, and the activities of CAT and SOD were induced in the leaves by
      PBZ. Moreover, the content of vitamin C, vitamin E and CAT activity were higher
      in relation to water-deficit stress and PBZ treatments. This indicates that PBZ
      induced a number of some physiological and biochemical adaptations (maintaining
      growth and RWC, decreasing EL and proline content, increasing the vitamin C and
      vitamin E levels, and CAT and SOD activities) that enable the Curcuma plant to
      tolerate drought.

PMID- 30294220
TI  - Phytochemical and taxonomic evaluation of Rhazya stricta in Saudi Arabia.
AB  - Rhazya stricta Decne is an important medicinal species used in indigenous
      medicinal herbal drugs to cure various diseases in South Asia (Pakistan, India
      and Afghanistan) and in the Middle East (e.g. Saudi Arabia, Qatar, United Arab
      Emirates (UAE), Iran and Iraq). Some of its alkaloids have been reported to have
      anticancerous properties. The aim of our study is to examine the morphological
      and taxonomical parameters for R. stricta in the Saudi Arabia; concentrations and
      distributions of some secondary metabolites; and also to determine the
      antioxidant and free radical scavenging activity. The results of present study
      showed that there was no influence of environment on the structure of stomata and
      trichomes as studying species with R. stricta. In conclusion our study shows no
      trichomes on leaf of R. stricta it is glabrous, whereas, variations between many
      secondary metabolites such as flavonoids and phenolic compounds occurred in
      response to changing climatic conditions.

PMID- 30294221
TI  - Bioengineered silver nanoparticles using Curvularia pallescens and its fungicidal
      activity against Cladosporium fulvum.
AB  - Microorganisms based biosynthesis of nanomaterials has triggered significant
      attention, due to their great potential as vast source of the production of
      biocompatible nanoparticles (NPs). Such biosynthesized functional nanomaterials
      can be used for various biomedical applications. The present study investigates
      the green synthesis of silver nanoparticles (Ag NPs) using the fungus Curvularia
      pallescens (C. pallescens) which is isolated from cereals. The C. pallescens cell
      filtrate was used for the reduction of AgNO3 to Ag NPs. To the best of our
      knowledge C. pallescens is utilized first time for the preparation of Ag NPs.
      Several alkaloids and proteins present in the phytopathogenic fungus C.
      pallescens were mainly responsible for the formation of highly crystalline Ag
      NPs. The as-synthesized Ag NPs were characterized by using UV-Visible
      spectroscopy, X-ray diffraction and transmission electron microscopy (TEM). The
      TEM micrographs have revealed that spherical shaped Ag NPs with polydisperse in
      size were obtained. These results have clearly suggested that the biomolecules
      secreted by C. pallescens are mainly responsible for the formation and
      stabilization of nanoparticles. Furthermore, the antifungal activity of the as
      prepared Ag NPs was tested against Cladosporium fulvum, which is the major cause
      of a serious plant disease, known as tomato leaf mold. The synthesized Ag NPs
      displayed excellent fungicidal activity against the tested fungal pathogen. The
      extreme zone of reduction occurred at 50 MUL, whereas, an increase in the
      reduction activity is observed with increasing the concentration of Ag NPs. These
      encouraging results can be further exploited by employing the as synthesized Ag
      NPs against various pathogenic fungi in order to ascertain their spectrum of
      fungicidal activity.

PMID- 30294222
TI  - Changes in protein quantities of phosphoenolpyruvate carboxylase and Rubisco
      activase in various wheat genotypes.
AB  - In early seedlings of wheat genotypes two isoforms of Rubisco activase with
      molecular weights of 42 and 46 kDa are expressed. Amounts of both isoforms
      significantly increase in early seedlings of the durum wheat genotype Barakatli
      95 exposed to salt stress. But at the beginning of the tillering stage, the
      changes in quantities of both RCA isoforms are different in durum and bread wheat
      genotypes subjected to a 3-day drought stress. In the leaves of the early
      seedlings of the studied wheat genotypes exposed to drought stress quantities of
      PEPC subunits increase compared to the control but they remain relatively stable
      in early roots and germinating seeds. However, quantities of its subunits
      decrease sharply in roots and germinating seeds of early seedlings under the
      influence of 100 mM NaCl. In flag leaves and ear elements of the Barakatli-95
      genotype grown under normal water supply conditions protein quantities of PEPC
      subunits change differently depending on time. Changes in protein quantities of
      RCA, PEPC and Rubisco enzymes have been studied comparatively in ear elements and
      flag leaves after the fourth day of anthesis.

PMID- 30294223
TI  - Changes in radical scavenging activity of normal, endoreduplicated and
      depolyploid root tip cells of Allium cepa.
AB  - The plant cell responds to abiotic stress conditions by adjusting its cellular
      metabolism and various defensive mechanisms. Cellular metabolism involves changes
      in the cell cycle, in which the cell undergoes repeated rounds of endocycles
      leading to polyploidization. Defense mechanisms such as role of antioxidants are
      a key to understand plant adaptation. The present work describes
      endoreduplication and radical scavenging activity as two different defense
      mechanisms adapted by plants for their survival under stress condition. The work
      describes linkage of these two processes with each other under abiotic stress.
      Endoreduplicated root tip cells of Allium cepa were depolyploidized by exogenous
      phytohormones. Further, free radical scavenging activity from normal,
      endoreduplicated and depolyploidized root tips cells was observed to understand
      the role of phytohormones. Elevated free radical scavenging potential was
      observed in endoreduplicated cells compared to normal and depolyploidized cells.
      Based on these results, it was concluded that endoreduplication and antioxidant
      pathways are linked with each other through phytohormonal activities. The
      concentration of auxin and cytokinin regulates the activity of ascorbate oxidase
      enzyme, which in turn maintains the concentration of AsA within the cell. AsA
      level directs the prolyl-hydroxylation process of cell division proteins in
      quiescent center cells either toward endoreduplication process or cell division
      process.

PMID- 30294224
TI  - Effects of hematite and ferrihydrite nanoparticles on germination and growth of
      maize seedlings.
AB  - Engineered iron oxide nanoparticles (IO-NPs) have been used extensively for
      environmental remediation. It may cause the release IO-NPs to the environment
      affecting the functions of ecosystems. Plants are an important component of
      ecosystems and can be used for the evaluation of overall fate, transport and
      exposure pathways of IO-NPs in the environment. In this work, the effects of
      engineered ferrihydrite and hematite NPs on the germination and growth of maize
      are studied. The germination and growth of maize were done with treatments at
      different concentrations of hematite and ferrihydrite NPs, namely 1, 2, 4, and 6
      g/L. Biological indicators of toxicity or stress in maize seedlings were not
      observed in treatments with engineered hematite and ferrihydrite NPs. In
      contrast, the NPs treatments increased the growth of maize and the chlorophyll
      content, except for hematite NPs at 6 g/L, where non-significant effects were
      found. The translocation of engineered ferrihydrite and hematite NPs in maize
      stems was demonstrated using confocal laser scanning microscopy.

PMID- 30294225
TI  - A herbal formula, comprising Panax ginseng and bee-pollen, inhibits development
      of testosterone-induced benign prostatic hyperplasia in male Wistar rats.
AB  - A recent study reported that Panax ginseng (P. ginseng) has a protective effect
      on the development of benign prostatic hyperplasia (BPH). KH053 is used as a new
      herbal prescription consisting of P. ginseng and bee-pollen. The present study
      aimed to investigate whether the KH053 has inhibition effects on the development
      of benign prostatic hyperplasia (BPH) using an animal model with testosterone
      induced BPH. The experiment was carried out in forty male Wistar 7 week old rats
      that were divided into four groups (control group, BPH group, positive group, and
      KH053 group). One group was used as the control and the three groups received
      subcutaneous injections of testosterone 20 mg/kg for 4 weeks to induce BPH. One
      of them received KH053 by oral gavage daily at doses of 200 mg/kg concurrently
      with the testosterone. The positive group received finasteride at a dose of 1
      mg/kg with testosterone. After 4 weeks, all rats were sacrificed and analyzed for
      prostate weight, and growth factors. Results revealed that, compared to rats in
      the BPH group, KH053 showed that the prostate weight and dihydrotestosterone
      (DHT) levels in serum were significantly decreased and the decreases in
      hyperplasia in prostate were also observed. In addition, immunohistochemistry
      (IHC) also revealed that the protein expressions of growth factors [transforming
      growth factor beta1 (TGF-beta1) and vascular endothelial growth factor (VEGF)] in
      prostate tissue were decreased in the KH053 group. In conclusion, these results
      suggest that KH053, comprising P. ginseng and bee-pollen, inhibits the
      development of BPH in Wistar rat model and might be used as functional food for
      BPH.

PMID- 30294226
TI  - Berberine improves the intestinal antioxidant status of laboratory mice, Mus
      musculus.
AB  - Oral administration of berberine chloride to mice induced an obvious enhancement
      in jejunal health status as expressed by the significant reduction of apoptotic
      cells within the intestinal villi from 15.5 to 8.3 apoptotic cell/10 VCU. In
      addition, jejunal antioxidant biomarkers were significantly improved as revealed
      by the increase in the activities of catalase and glutathione peroxidase enzymes
      with a concurrent increase in reduced glutathione levels and total antioxidant
      capacity. Also, it was associated with a significant decrease in oxidative damage
      biomarkers of hydrogen peroxides, malondialdehyde, nitrite/nitrate, inducible
      nitric oxide synthase and protein carbonyl content. Moreover, BBR treatment
      induced a reduction in the pro-inflammatory cytokine, TNF-alpha by about 40%. It
      is highly recommended to use berberine as food supplements or as natural drug
      therapy to enhance the antioxidant status within the intestinal tissue.

PMID- 30294227
TI  - Systematic studies on the Zygophyllaceae of Saudi Arabia: A new variety and new
      variety combination in Tetraena.
AB  - During 2013-2014, fresh material of Tetraena alba was collected from two
      localities in Saudi Arabia. Detailed morphological examination of these specimens
      revealed that there is a new variety of this species, for which the name T. alba
      var. arabica is proposed. Fresh material of Zygophyllum amblyocarpum was also
      collected from a different locality, and based on its characteristics is
      transferred to Tetraena with the new combination T. alba var. amblyocarpa. T.
      alba and its varieties are illustrated and morphological characters supplied to
      differentiate among them.

PMID- 30294228
TI  - Alteration in antioxidant genes expression in some fish caught from Jeddah and
      Yanbu coast as a bio-indicator of oil hydrocarbons pollution.
AB  - The mRNA expression profile of some antioxidant genes in skin, gills, livers, and
      muscles of Siganus canaliculatus and Epinephelus morio was used as an indicator
      of petroleum hydrocarbons pollution in six areas at Jeddah and Yanbu coasts in
      KSA. Total petroleum hydrocarbons (TPHs) were determined in both sea water and
      sediments collected from the studied areas. The mRNA expression levels of
      superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR),
      glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were determined.
      The highest level of total petroleum hydrocarbons was observed in front of the
      petromine refinery at Jeddah and in S. canaliculatus when compared to E. morio.
      There was a significant high expression level of studied antioxidant enzymes
      genes in the polluted areas and the level of the expression profile tended to
      correlate with the degree of pollution and fish species feed habit. This was
      confirmed by the level of MDA which in the same way increased with an increase in
      the level of total hydrocarbons. In conclusion; the expression profile of
      antioxidant enzymes of S. canaliculatus and E. morio tissues can be used as a
      strong bio-indicator of total hydrocarbons pollution especially in S.
      canaliculatus.

PMID- 30294229
TI  - A re-examination of the Salicornias (Amaranthaceae) of Saudi Arabia and their
      polymorphs.
AB  - During the period from 1964 to 1999 Saudi Arabian species of Salicornia were
      wrongly treated under the European species, S. europaea L. Recent explorations
      proved that there are two separate allopatric species of Salicornia in Saudi
      Arabia, one inhabiting the inland salt-marshes of the Najd (highlands) and the
      other inhabiting the Arabian Gulf Coast (lowlands). Morphological, ecological and
      exploratory studies confirm that they are two distinct species. The two species
      differ in features of bark, axillary spikes, basal vegetative segment(s) of
      spike, fertile segments, colour of senescent plants, and flowering, fruiting and
      germination phenology. As both the species have been described earlier from Iran,
      they are now new records for Saudi Arabia. The species are, S. persica ssp.
      iranica (Akhani) Kadereit & Piirainen and S. sinus-persica Akhani. S. sinus
      persica, of which the status was thought doubtful has been confirmed. Both the
      species have been described and illustrated. Each species comprises a number of
      polymorphs. As leaves and flowers are rudimentary, confusing species
      circumscriptions, a proliferation of binomials has resulted in the taxonomy of
      Salicornia. To mitigate such confusion, the full range of variability of the
      Saudi Arabian species has been documented.

PMID- 30294230
TI  - BmNPV-miR-415 up-regulates the expression of TOR2 via Bmo-miR-5738.
AB  - MicroRNAs (miRNAs) have emerged as key players in host-pathogen interaction and
      many virus-encoded miRNAs have been identified (computationally and/or
      experimentally) in a variety of organisms. A novel Bombyx mori nucleopolyhedrosis
      virus (BmNPV)-encoded miRNA miR-415 was previously identified through high
      throughput sequencing. In this study, a BmNPV-miR-415 expression vector was
      constructed and transfected into BmN cells. The differentially expressed protein
      target of rapamycin isoform 2 (TOR2) was observed through two-dimensional gel
      electrophoresis and mass spectrometry. Results showed that TOR2 is not directly a
      target gene of BmNPV-miR-415, but its expression is up-regulated by BmNPV-miR-415
      via Bmo-miR-5738, which could be induced by BmNPV.

PMID- 30294231
TI  - Extreme effects of Seabuckthorn extracts on influenza viruses and human cancer
      cells and correlation between flavonol glycosides and biological activities of
      extracts.
AB  - Seabuckthorn is a medicinal plant that is used to prevent cold. It was tested for
      its metabolic content followed by activity against cancer and virus. The
      metabolic distribution of different polarity solvent extractions from the leaves
      was analyzed by LC-MS/MS. Flavonol glycoside contents in EA and Bu extracts were
      higher than MeOH and DW was observed. MeOH and EA extracts recorded high activity
      against influenza A/PR virus with IC50 of 7.2 MUg/mL and 10.3 MUg/mL compared
      with known drug Oseltamivir of 60.3 MUg/mL. A similar trend showed in influenza
      A/Victoria virus. In case of influenza B viruses such as B/Lee and B/Maryland, EA
      extract (2.87 MUg/mL and 4.5 MUg/mL of IC50) emerged strongest among other
      extracts and Oseltamivir (103.73 MUg/mL and 71.6 MUg/mL). Each extract showed
      potent anticancer activities. Interestingly, Bu extract showed stronger
      anticancer activity against human cancer cells such as NCL-H1299, HeLa, SKOV and
      Caski (8.2 MUg/mL, 8.6 MUg/mL, 18.2 MUg/mL and 9.2 MUg/mL of IC50) respectively.
      Correlation study reveals that aglycones and flavonol mono-glycosides highly
      correlated with anti-influenza activities but not correlated with anticancer
      activities. Reversely, di-glycosides and tri-glycosides have a high correlation
      with cytotoxic effect with both normal and cancer cells. Therefore, this study
      provides significant information concerning Seabuckthorn for further medicinal
      drug development.

PMID- 30294232
TI  - Alterations in the antibacterial potential of Synechococcus spp. PCC7942 under
      the influence of UV-B radiations on skin pathogens.
AB  - Marine organisms are seen as a source of novel drugs and the discovery of new
      pharmaceutical is increasingly in demand. Cyanobacteria are regarded as a
      potential target for this as antibacterial, antiviral, antifungal, algicide and
      cytotoxic activities have been reported in these organisms. They have been
      identified as a new and rich source of bioactive compounds belonging to
      diversified groups. Radiation in the UV-B range interferes with various metabolic
      reactions by generating free radicals and active oxygen species. These
      deleterious compounds are inactivated by antioxidants. Among them are the
      carotenoids and phycocyanin which protect against photodynamic action in
      different ways. Stress plays an important role in the production of bioactive
      metabolites from organisms. Synechococcus spp. PCC7942 was studied for
      antibacterial activity against various pathogenic bacteria resistant to a number
      of available antibiotics after being exposed to UV-B radiation. The antibacterial
      activity of Synechococcus spp. PCC7942 was studied on five potent skin pathogens.
      The highest antibacterial activity was seen the methanol extracts of 24 h UV-B
      exposed cultures of Synechococcus spp. PCC7942. It can be concluded that there
      was moderate antibacterial activity. Results showed stress, solvent and dose
      dependent activity. This antibacterial activity might be due to the enhanced
      synthesis of carotenoids and phycocyanin under UV-B stress. The purpose of the
      present study was to relate the inhibitory effects of the cyanobacterial
      compounds specifically on skin pathogens with exposure to UV-B radiation as UV
      protecting compounds are already reported in these organisms.

PMID- 30294233
TI  - Foot care practices of diabetic patients in Saudi Arabia.
AB  - Diabetic foot is a serious complication that causes lower extremity amputations.
      The aim of this study was to identify the patient's awareness about risk factors
      for diabetic foot disease and to explore the knowledge and foot care practices
      among diabetic patients in a Saudi population. This cross-sectional study was
      conducted in King Khalid University Hospital (KKUH), King Abdulaziz University
      Hospital (KAUH), King Fahad Medical City, National Guard Hospital, Military
      Hospital, and Prince Salman Hospital capital city of Saudi Arabia. Patients were
      eligible if they had diabetes foot disease, signed the consent form, and
      completed the questionnaire. We selected 350 patients from different hospitals
      between November-2011 and April-2012. The majority of patients (68%) were
      selected from King Saud University hospitals. The mean age of patients was 50.87
      +/- 15.9 years with a range of 20-90 years. The majority of patients were male
      (64.3%) and had a family history of hypertension (55.4%), high total cholesterol
      (58.6%), and other diabetes (58.9%). A family history of smoking, a major risk
      factor for diabetic foot, was found in 20.3% of cases. Sixty percent of the
      patients were using oral medications, 27.1% were using insulin therapy, 10% were
      using both oral and insulin therapies, and 10% were on diet. In our study, 19.4%
      of participants were illiterate while 80.6% had a high school or university level
      education. Our findings also revealed that some patients had a lack of knowledge
      concerning diabetic foot disease and future complications. Patients are unaware
      of the risk factors for diabetes foot and practice poor foot care. Awareness
      programs should be mandatory in all hospitals and diabetes clinics to help
      compensate for the lack of awareness and lack of podiatric educational services.
      Such programs may decrease the risk of diabetes foot disease.

PMID- 30294234
TI  - Effect of Zinc nanoparticles on oxidative stress-related genes and antioxidant
      enzymes activity in the brain of Oreochromis niloticus and Tilapia zillii.
AB  - This study was carried out to determine the median lethal concentrations (LC50)
      of Zinc nanoparticles (ZnNPs) on Oreochromis niloticus and Tilapia zillii. The
      biochemical and molecular potential effects of ZnNPs (500 and 2000 MUg L-1) on
      the antioxidant system in the brain tissue of O. niloticus and T. zillii were
      investigated. Four hundred fish were used for acute and sub-acute studies. ZnNP
      LC50 concentrations were investigated in O. niloticus and T. zillii. The effect
      of 500 and 2000 MUg L-1 ZnNPs on brain antioxidants of O. niloticus and T. zillii
      was investigated. The result indicated that 69 h LC50 was 5.5 +/- 0.6 and 5.6 +/-
      0.4 for O. nilotica and T. zillii, respectively. Fish exposed to 500 MUg L-1
      ZnNPs showed a significant increase in reduced glutathione (GSH), total
      glutathione (tGSH) levels, superoxide dismutase (SOD), catalase (CAT),
      glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S
      transferase (GST) activity and gene expression. On the contrary, malondialdehyde
      (MDA) levels significantly decreased. Meanwhile, fish exposed to 2000 MUg L-1
      ZnNPs showed a significant decrease of GSH, tGSH levels, SOD, CAT, GR, GPx and
      GST activity and gene expression. On the contrary, MDA levels significantly
      increased. It was concluded that, the 96 h LC50 of ZnNPs was 5.5 +/- 0.6 and 5.6
      +/- 0.4 for O. nilotica and T. zillii, respectively. ZnNPs in exposure
      concentrations of 2000 MUg/L induced a deleterious effect on the brain
      antioxidant system of O. nilotica and T. zillii. In contrast, ZnNPs in exposure
      concentrations of 500 MUg L-1 produced an inductive effect on the brain
      antioxidant system of O. nilotica and T. zillii.

PMID- 30294235
TI  - Superintendence of antimicrobial resistance observed in bacterial flora isolated
      from human faecal carriage in Vellore, India.
AB  - A frequent cross-sectional study was conducted to determine the patterns of
      antimicrobial resistance in 296 bacterial strains isolated from in-patient faecal
      samples of Government Vellore Medical College and Hospital, Vellore. Isolation
      and identification of bacterial strains were done using enrichment media,
      selective media, and biochemical tests. Antimicrobial susceptibility testing by
      the disc diffusion method and minimal inhibitory concentration method was
      conducted and the strains were subjected to extended spectrum beta-lactamases
      screening. Antibiotic sensitivity pattern of Staphylococcus spp. showed oxacillin
      resistance. Almost all the strains were sensitive to linezolid, vancomycin,
      gentamycin and chloramphenicol. In gram negative isolates ciprofloxacin and
      tobramycin showed better sensitivity and ceftazidime showed a higher percentage
      of resistance by MIC. Out of 250 isolates, Enterobacteriaceae showed positive for
      86/250, 82/250 and 94/250 isolates and 3/10, 4/10 and 4/10 non-Enterobacteriaceae
      isolates were found to be positive for CTX-M gene, TEM gene and SHV gene,
      respectively. This study helps to assess/analyse the relation between the
      spectrum of microorganisms present in various grades of faecal carriage and their
      susceptibility pattern in this part of the Vellore town.

PMID- 30294236
TI  - Pod, seed traits and cytotaxonomic studies of some Vicia narbonensis L.
      accessions (Fabaceae).
AB  - This study aimed to characterize eight accessions of Vicia narbonensis L.
      originated from different Mediterranean countries. The cytology of these species
      is rarely known despite the fact of its great socio-economical and ecological
      interest in these arid and semi-arid zones. This work aimed mainly to
      characterize the karyotype, morphological pod and seed traits of the species.
      Karyotypes of all accessions were similar to a diploid number of 2n = 2x = 14.
      All the accessions have submetacentric chromosomes with a secondary constriction
      attached to the long arm of pair VII close to the centromere. Variation in
      chromosome size was observed; it ranged from 5.86 MUm to 7.62 MUm. Indices of
      karyotype asymmetry were calculated as the total form percentage (TF%) and
      symmetric indices (Syi) which ranged from 33.75% to 35.42% and from 51.01% to
      54.85%, respectively. The predominance of submetacentric chromosomes indicated
      that the karyotype is symmetrical and can be considered as primitive. However,
      the analysis of quantitative parameters measured on pods and seeds showed a
      significant variation between accessions. A relationship between centromeric
      index and the pod beak length was found. Estimation of phenotypic diversity using
      the Shannon diversity index (H') showed that the length, the seed color and the
      number of seeds per pod are the most polymorphic traits with respectively, H' =
      0.92, 0.80 and 0.83. Cluster analysis of karyological, pod and seed traits showed
      four groups of accessions. This clustering is partially due to the geographical
      origin of the studied accessions. The variation in chromosome size, pod and seed
      traits could offer potentially valuable genetic resources for the improvement of
      V. narbonensis which is considered as neglected and underutilized crop species
      (NUCS).

PMID- 30294237
TI  - Molecular typing of phlebotomine sand flies in al-madinah and asir regions, Saudi
      Arabia using PCR-RFLP of 18S ribosomal RNA gene.
AB  - Studies on the distribution of sand flies are important for the control of
      leishmaniasis in endemic and neighboring areas. In the present study polymerase
      chain reaction (PCR)-restriction fragment length polymorphism (RFLP) was used to
      identify the distribution of sand flies in Al-Madinah and Asir Regions of Saudi
      Arabia using PCR-RFLP of 18S ribosomal RNA gene. Based on the morphological
      characteristics, the sand flies were differentiated into seven species viz.,
      Phlebotomus papatasi, Phlebotomus sergenti, Phlebotomus bergeroti, Sergentomyia
      clydei, Sergentomyia antennata, Sergentomyia fallax and Sergentomyia schwetzi.
      PCR-RFLP of 18S ribosomal RNA (rRNA) genes with eight different restriction
      enzymes resulted in species-specific agarose gel electrophoresis banding
      patterns. Of the eight restriction enzymes used, not a single restriction enzyme
      by itself could separate species belonging to the same genera (like P. papatasi
      and P. sergenti by AseI) as well as those belonging to different genera (like P.
      papatasi and S. clydei by AseI). We therefore conclude that the genetic diversity
      within sand fly species based on PCR-RFLP technique was nonspecific. Studies are
      in progress to study the viability of alternate techniques like low-stringency
      single specific primer polymerase chain reaction which can be used for molecular
      typing.

PMID- 30294238
TI  - Description of a methanotrophic strain BOH1, isolated from Al-Bohyriya well, Al
      Ahsa City, Saudi Arabia.
AB  - Methanotrophic bacteria have a unique ability to utilize methane as their carbon
      and energy sources. Therefore, methanotrophs play a key role in suppressing
      methane emissions from different ecosystems and hence in alleviating the global
      climate change. Despite methanotrophs having many ecological, economical and
      biotechnological applications, little is known about this group of bacteria in Al
      Ahsa. Therefore, the main objective of the current work was to expand our
      understanding of methane oxidizing bacteria in Al-Ahsa region. The specific aim
      was to describe a methanotrophic strain isolated from Al-Bohyriya well, Al-Ahsa
      using phenotypic, genotypic (such as 16S rRNA and pmoA gene sequencing) and
      phylogenetic characterization. The results indicated that the strain belongs to
      the genus Methylomonas that belongs to Gammaproteobacteria as revealed by the
      comparative sequence analysis of the 16S rRNA and pmoA genes. There is a general
      agreement in the profile of the phylogenetic trees based on the sequences of
      16srRNA and pmoA genes of the strain BOH1 indicating that both genes are
      efficient taxonomic marker in methanotrophic phylogeny. The strain possesses the
      particulate but not the soluble methane monooxygenase as a key enzyme for methane
      metabolism. Further investigation such as DNA:DNA hybridization is needed to
      assign the strain as a novel species of the genus Methyomonas and this will open
      the door to explore the talents of the strain for its potential role in
      alleviating global warming and biotechnological applications in Saudi Arabia such
      as bioremediation of toxic by-products released in oil industry. In addition, the
      strain enhances our knowledge of methanotrophic bacteria and their adaptation to
      desert ecosystems.

PMID- 30294239
TI  - Ultrastructural differentiation of spermiogenesis in Scincus scincus (Scincidae,
      Reptilia).
AB  - Background: Knowledge of spermiogenesis in reptiles, especially in lizards, is
      very limited. Lizards found in Arabian deserts have not been considered for
      detailed studies due to many reasons and the paucity of these animals. Therefore,
      we designed a study on the differentiation and morphogenesis of spermiogenesis,
      at an ultrastructural level, in a rare lizard species, Scincus scincus. Results:
      The spermiogenesis process includes the development of an acrosomal vesicle,
      aggregation of acrosomal granules, formation of subacrosomal nuclear space, and
      nuclear elongation. A role for manchette microtubules was described in nuclear
      shaping and organelle movement. During head differentiation, the fine granular
      chromatin of the early spermatid is gradually replaced by highly condensed
      contents in a process called chromatin condensation. Furthermore, ultrastructural
      features of sperm tail differentiation in S. scincus were described in detail.
      The commencement was with caudal migration toward centrioles, insertion of the
      proximal centriole in the nuclear fossa, and extension of the distal centrioles
      to form the microtubular axoneme. Subsequently, tail differentiation consists of
      the enlargement of neck portion, middle piece, the main and end pieces.
      Conclusions: This study aids in the understanding of different aspects of
      spermiogenesis in the lizard family and unfurls evolutionary links within and
      outside reptiles.

PMID- 30294240
TI  - Statistical optimization of antifungal iturin A production from Bacillus
      amyloliquefaciens RHNK22 using agro-industrial wastes.
AB  - Biosurfactants are secondary metabolites with surface active properties and have
      wide application in agriculture, industrial and therapeutic products. The present
      study was aimed to screen bacteria for the production of biosurfactant, its
      characterization and development of a cost effective media formulation for iturin
      A production. A total of 100 bacterial isolates were isolated from different
      rhizosphere soil samples by enrichment culture method and screened for
      biosurfactant activity. Twenty isolates were selected for further studies based
      on their biosurfactant activity [emulsification index (EI%), emulsification assay
      (EA), surface tension (ST) reduction] and antagonistic activity. Among them one
      potential isolate Bacillus sp. RHNK22 showed good EI% and EA with different
      hydrocarbons tested in this study. Using biochemical methods and 16S rRNA gene
      sequence, it was identified as Bacillus amyloliquefaciens. Presence of iturin A
      in RHNK22 was identified by gene specific primers and confirmed as iturin A by
      FTIR and HPLC. B. amyloliquefaciens RHNK22 exhibited good surface active
      properties and antifungal activity against Sclerotium rolfsii and Macrophomina
      phaseolina. For cost-effective production of iturin A, 16 different agro
      industrial wastes were screened as substrates, and Sunflower oil cake (SOC) was
      favouring high iturin A production. Further, using response surface methodology
      (RSM) model, there was a 3-fold increase in iturin A production (using SOC 4%,
      inoculum size 1%, at pH 6.0 and 37  degrees C temperature in 48 h). This is the
      first report on using SOC as a substrate for iturin A production.

PMID- 30294241
TI  - Pollination ecology of Acacia gerrardii Benth. (Fabaceae: Mimosoideae) under
      extremely hot-dry conditions.
AB  - Talh trees (Acacia gerrardii Benth.) are acacias that are native to the arid and
      semiarid Africa and west Asia. We investigated the flowering biology, pod set and
      flower visitors of Talh and discussed the role of these visitors in pollen
      transfer. The Talh trees blossomed laterally on the nodes of one-year-old twigs.
      Each node produced 21 flower buds seasonally. Each flower bud opened to a flower
      head (FH) of 60 florets. The bagged FHs podded significantly (p ? 0.05) less than
      did the unbagged FHs. The FHs were visited by 31 insect species (25 genera, 16
      families and 5 orders). The major taxa were honeybees, megachilids, butterflies,
      ants, beetles and thrips. Each of honeybees, megachilids and beetles showed a
      significant (p ? 0.05) hourly pattern, while each of butterflies, ants and thrips
      had no hourly pattern (p > 0.05). Furthermore, some birds and mammals touched the
      Talh FHs. Talh trees evolved a mass flowering behavior to face pre- and post
      flowering obstacles. Megachilids seemed to play the major effort of zoophily
      because of their relatively high numbers of individuals and species and their
      effective movement behavior on the FH surface. Nevertheless, honeybees and other
      insects and vertebrate taxa also contributed to the pollen transfer. These
      results greatly contribute to our understanding of the pollination ecology of
      acacias, especially Arabian acacias.

PMID- 30294242
TI  - A sustainable approach to empower the bio-based future: upgrading of biomass via
      process intensification.

PMID- 30294243
TI  - Indian philosophical foundations of spirituality at the end of life.
AB  - Growing understanding of spirituality at the end of life demands more theoretical
      research on the subject. Empirical studies have highlighted the need for
      exploring philosophical and cultural concepts to facilitate a fuller
      understanding of spirituality at the end of life. This paper explores Indian
      philosophy to inform the conceptualisation of spirituality at the end of life in
      the Indian context. Three key themes from discourses on spirituality at the end
      of life have been analysed: the concept of the human person, the purpose of life
      and the meaning of death. The human person is from and of the Divine, eternal and
      is capable of cognition and experience. The purpose of human life is to unite
      with the ultimate Reality, the Divine, by living life righteously according to
      prescribed ways and by achieving detachment from the illusion of the world. Death
      is part of life and not that which ends it. The moment of death is an opportunity
      for the ultimate transformation, Moksha. Analysing these philosophical
      foundations can provide the contextual frame for understanding the spiritual
      needs of palliative care patients and their families and the possibility of
      developing culturally relevant approaches to providing spiritual care at the end
      of life.

PMID- 30294244
TI  - Development of an epiphyte indicator of nutrient enrichment: threshold values for
      seagrass epiphyte load.
AB  - Metrics of epiphyte load on macrophytes were evaluated for use as quantitative
      biological indicators for nutrient impacts in estuarine waters, based on review
      and analysis of the literature on epiphytes and macrophytes, primarily
      seagrasses, but including some brackish and freshwater rooted macrophyte species.
      An approach is presented that empirically derives threshold epiphyte loads which
      are likely to cause specified levels of decrease in macrophyte response metrics
      such as biomass, shoot density, percent cover, production and growth. Data from
      36 studies of 10 macrophyte species were pooled to derive relationships between
      epiphyte load and -25 and -50% seagrass response levels, which are proposed as
      the primary basis for establishment of critical threshold values. Given multiple
      sources of variability in the response data, threshold ranges based on the range
      of values falling between the median and the 75th quantiles of observations at a
      given seagrass response level are proposed rather than single, critical point
      values. Four epiphyte load threshold categories - low, moderate, high, very high,
      are proposed. Comparison of values of epiphyte loads associated with 25 and 50%
      reductions in light to macrophytes suggest that the threshold ranges are
      realistic both in terms of the principle mechanism of impact to macrophytes and
      in terms of the magnitude of resultant impacts expressed by the macrophytes. Some
      variability in response levels was observed among climate regions, and additional
      data collected with a standardized approach could help in the development of
      regionalized threshold ranges for the epiphyte load indicator.

PMID- 30294245
TI  - Emergy-based indicators for evaluating ecosystem health: A case study of three
      benthic ecosystem networks influenced by coastal upwelling in northern Chile (SE
      Pacific coast).
AB  - It has been hypothesized that ecosystem health describes the state in which all
      processes operating within an ecosystem are functioning at a level of optimum
      efficiency to maximize system empower. In this study, systems analysis of
      networks and information flows is used within this definition of ecosystem health
      to assess the condition of the benthic ecosystems in three coastal bays in
      northern Chile. These highly productive ecosystems are characterized by the
      inflow of cold, nutrient-rich waters of low oxygen concentration derived from
      coastal upwelling of deep waters and the interruption of upwelling flow during El
      Nino events when warmer waters with higher oxygen and lower nutrient
      concentrations enter these coastal systems. Also, these ecosystems support
      important artisanal benthic fisheries and are affected by industrial activities
      in the coastal zone. Energy Systems Theory (EST) and Emergy Analysis (EA) were
      applied to quantify the health of these benthic ecosystems and evaluate
      differences in their structure, organization and functional capacities, which are
      related to their emergy signatures. The marked dominance of these benthic
      ecosystems by nitrate from upwelling resulted in unbalanced emergy signatures,
      suggesting less development and system diversity compared to other coastal
      ecosystems with more balanced emergy signatures. Macro-descriptors and network
      properties, such as emergy-based ascendency and the quality-adjusted Shannon
      diversity index were highest for Mejillones Bay, followed by Antofagasta and then
      Tongoy Bay. The Average Mutual Information (AMI) index adjusted for energy
      quality and the emergy-based A/C (ascendency to capacity) ratio, were higher for
      Tongoy Bay, suggesting functional differences in health among the three
      ecosystems. Thus, the emergy-based macro descriptors and other indicators used in
      our analysis indicate that the benthic networks examined have different
      structural and functional characteristics that lead to different
      characterizations of their states of health. As a result of this complexity,
      management policies should be implemented within a systemic context for analysis
      that considers all the factors determining the relative health of each ecosystem.

PMID- 30294246
TI  - A case-control study on the association of abdominal obesity and
      hypercholesterolemia with the risk of colorectal cancer.
AB  - BACKGROUND: Obesity has frequently been associated with the dyslipidemic state
      and with the risk of various chronic diseases. OBJECTIVE: The objective of this
      study was to determine the relationship between obesity and blood lipids with a
      risk of colorectal cancer (CRC). METHODOLOGY: Histologically confirmed CRC
      patients from five local hospitals were matched with cancer-free controls for
      age, gender, and ethnicity (n = 140: 280). The study participants underwent
      physical assessment for the presence of obesity and 10 mL of fasting blood was
      drawn for blood lipid analysis. RESULTS: In this study, abdominal obesity
      significantly doubled the risk of CRC (adjusted odds ratio [AOR] =1.69, 95%
      confidence interval [CI] = 1-2.83). Hypercholesterolemia and low high-density
      lipoprotein cholesterol (HDL) increased the risk of CRC more than twofolds (AOR =
      2.6, 95% CI = 1.7-3.9 and AOR = 3.8, 95% CI = 2.3-6.3, respectively). Abdominal
      obesity and hypercholesterolemia synergically doubled the risk of CRC (AOR = 2.0,
      95% CI = 1-4). Low-HDL has shown no synergic association with other dyslipidemic
      states with an increased CRC risk. CONCLUSION: Improving abdominal obesity,
      hypercholesterolemia, and low HDL may be a clinically relevant strategy to reduce
      the risk of CRC among Malaysians.

PMID- 30294247
TI  - Role of aberrant glycosylation enzymes in oral cancer progression.
AB  - BACKGROUND: Carcinogenesis, a multistep process involves sequential changes
      during neoplastic transformation. The various hallmarks of cancer aid in cell
      survival, proliferation, and dissemination. Aberrant glycosylation, a recently
      defined hallmark of cancer, is influenced by glycosylation enzymes during
      carcinogenesis. Therefore, the present study measured alpha-2,3 and alpha-2,6
      sialyltransferase (ST), sialidase, and alpha-L-fucosidase activity in patients
      with oral precancerous conditions (OPC) and oral cancer patients. SUBJECTS: The
      study enrolled 100 oral cancer patients, 50 patients with OPC, 100 healthy
      controls, and 46 posttreatment follow-ups of oral cancer patients. Blood and
      saliva were collected from all the participants. MATERIALS AND METHODS: Sialidase
      activity was measured by spectrofluorimetric method, alpha-2,3 and alpha-2,6 ST
      by ELISA using biotinylated lectins, and alpha-L-fucosidase by spectrophotometric
      method. RESULTS: The results depicted increased levels of sialidase, alpha-2,3
      and alpha-2,6 ST, alpha-L-fucosidase in patients with OPC and oral cancer
      patients. Receiver operating characteristic curve indicated significant
      discriminatory efficacy in distinguishing controls and oral cancer patients for
      serum and salivary sialidase and alpha-L-fucosidase activity, and serum alpha-2,6
      ST. Furthermore, serum and salivary alpha-L-fucosidase activity and serum
      sialidase activity significantly distinguished controls and patients with OPC.
      Serum and salivary sialidase, alpha-L-fucosidase, and serum alpha-2,3 ST activity
      were higher in patients with metastasis as compared to nonmetastatic patients.
      Higher values of serum alpha-L-fucosidase activity were significantly associated
      with low-overall survival. CONCLUSION: The increased levels of enzymes correlated
      with tumor initiation, progression, and metastasis in oral cancer patients. The
      alterations in glycosyltransferases/glycosidases thus support the view of
      glycosylation as a hallmark of cancer.

PMID- 30294249
TI  - Optimization and Validation of a Microscale In vitro Method to Assess ?alpha
      Glucosidase Inhibition Activity.
AB  - Background: Microscale in vitro assays are fast, simple, and inexpensive, with
      reduced reagent quantities, waste, and experimental animal use. However, they
      have low reproducibility and low correlation with the results of in vivo models,
      possibly due to differences in precision and accuracy in methodologies between
      laboratories. Objective: The objective was the optimization and validation of an
      in vitro assay, carried out on microscale, to assess the inhibition of alpha
      glucosidase activity, which is indicative of antihyperglycemic activity. Methods:
      The optimization was carried out using a fractional factorial design taking into
      account the best inhibition percentage and the absorbance of the controls. With
      the optimized experimental conditions in hand, we carried out method validation.
      Results: The optimized conditions were as follows: enzyme concentration, 0.55
      U/mL; substrate concentration, 111.5 MUM; and 17.5 min incubation at 37 degrees
      C. A linear range between 100 and 310.2 MUg/mL of acarbose (r2 0.994) was
      established. The RSD was <2% and the % error was <3%. The Z factor was >0.96.
      This method was applied to four plant extracts, one of which was found to be very
      active. Conclusion: The method was found to be accurate, precise, selective,
      linear, and reliable in evaluating the antihyperglycemic activity of natural
      extracts in vitro.

PMID- 30294248
TI  - The Role of Liver-Directed Therapy in Metastatic Colorectal Cancer.
AB  - Purpose of Review: Colorectal cancer liver metastasis is a major clinical
      problem, and surgical resection is the only potentially curative treatment. We
      seek to discuss various liver-directed therapy modalities and explore their roles
      in the evolving realm of treatment strategies for metastatic colorectal cancer.
      Recent Findings: Clinical outcomes for patients with colorectal cancer liver
      metastases have improved as more patients undergo potentially curative resection
      and as the armamentarium of systemic treatment and liver-directed therapies
      continues to expand. Liver-directed therapies have been developed as adjuncts to
      improve resectability, employed in the adjuvant setting to potentially reduce
      local recurrence rates, and utilized in the palliative setting with the aim to
      improve overall survival. Summary: Ongoing research is expected to validate the
      role of these evolving therapeutic options, and determine how best to sequence
      and when to apply these therapies.

PMID- 30294250
TI  - Spatio-Temporal Dynamics of Intrinsic Networks in Functional Magnetic Imaging
      Data Using Recurrent Neural Networks.
AB  - We introduce a novel recurrent neural network (RNN) approach to account for
      temporal dynamics and dependencies in brain networks observed via functional
      magnetic resonance imaging (fMRI). Our approach directly parameterizes temporal
      dynamics through recurrent connections, which can be used to formulate blind
      source separation with a conditional (rather than marginal) independence
      assumption, which we call RNN-ICA. This formulation enables us to visualize the
      temporal dynamics of both first order (activity) and second order (directed
      connectivity) information in brain networks that are widely studied in a static
      sense, but not well-characterized dynamically. RNN-ICA predicts dynamics directly
      from the recurrent states of the RNN in both task and resting state fMRI. Our
      results show both task-related and group-differentiating directed connectivity.

PMID- 30294252
TI  - The Small World of Adult Hippocampal Neurogenesis.
AB  - Making mechanistic sense of genetically complex biological systems such as adult
      hippocampal neurogenesis poses conceptual and many practical challenges.
      Transcriptomics studies have helped to move beyond single-gene approaches and
      have greatly enhanced the accessibility to effects of greater numbers of genes.
      Typically, however, the number of experimental conditions compared is small and
      the conclusions remain correspondingly limited. In contrast, studying complex
      traits in genetic reference populations, in which genetic influences are varied
      systematically, provides insight into the architecture of relationships between
      phenotypes and putative molecular mechanisms. We describe that the correlation
      network among transcripts that builds around the adult neurogenesis phenotype and
      its endophenotypes is, as expected, a small-world network and scale free. The
      high degree of connectivity implies that adult neurogenesis is essentially an
      "omnigenic" process. From any gene of interest, a link to adult hippocampal
      neurogenesis can be constructed in just a few steps. We show that, at a minimum
      correlation of 0.6, the hippocampal transcriptome network associated with adult
      neurogenesis exhibits only two "degrees of separation." This fact has many
      interesting consequences for our attempts to unravel the (molecular) causality
      structure underlying adult neurogenesis and other complex biological systems. Our
      article is not written with the expert on network theory in mind but rather aims
      to raise interest among neurobiologists, active in neurogenesis and related
      fields, in network theory and analysis as a set of tools that hold great promise
      for coping with the study of "omnigenic" phenotypes and systems.

PMID- 30294251
TI  - Selective Depletion of CREB in Serotonergic Neurons Affects the Upregulation of
      Brain-Derived Neurotrophic Factor Evoked by Chronic Fluoxetine Treatment.
AB  - Neurotrophic factors are regarded as crucial regulatory components in neuronal
      plasticity and are postulated to play an important role in depression pathology.
      The abundant expression of brain-derived neurotrophic factor (BDNF) in various
      brain structures seems to be of particular interest in this context, as
      downregulation of BDNF is postulated to be correlated with depression and its
      upregulation is often observed after chronic treatment with common
      antidepressants. It is well-known that BDNF expression is regulated by cyclic AMP
      response element-binding protein (CREB). In our previous study using mice lacking
      CREB in serotonergic neurons (Creb1TPH2CreERT2 mice), we showed that selective
      CREB ablation in these particular neuronal populations is crucial for drug
      resistant phenotypes in the tail suspension test observed after fluoxetine
      administration in Creb1TPH2CreERT2 mice. The aim of this study was to investigate
      the molecular changes in the expression of neurotrophins in Creb1TPH2CreERT2 mice
      after chronic fluoxetine treatment, restricted to the brain structures implicated
      in depression pathology with profound serotonergic innervation including the
      prefrontal cortex (PFC) and hippocampus. Here, we show for the first time that
      BDNF upregulation observed after fluoxetine in the hippocampus or PFC might be
      dependent on the transcription factor CREB residing, not within these particular
      structures targeted by serotonergic projections, but exclusively in serotonergic
      neurons. This observation may shed new light on the neurotrophic hypothesis of
      depression, where the effects of BDNF observed after antidepressants in the
      hippocampus and other brain structures were rather thought to be regulated by
      CREB residing within the same brain structures. Overall, these results provide
      further evidence for the pivotal role of CREB in serotonergic neurons in
      maintaining mechanisms of antidepressant drug action by regulation of BDNF
      levels.

PMID- 30294253
TI  - Glycine-Histidine-Lysine (GHK) Alleviates Neuronal Apoptosis Due to Intracerebral
      Hemorrhage via the miR-339-5p/VEGFA Pathway.
AB  - Glycine-histidine-lysine (GHK) is a human tripeptide that enhances wound healing,
      exerts neuroprotective effects against neurodegenerative disease, and improves
      tissue regeneration. This study examined whether GHK can alleviate injury due to
      intracerebral hemorrhage (ICH). Briefly, adult Wistar rats in GHK pretreatment
      groups were injected with GHK (1 or 10 mg/kg, i.p.) every 24 h for 3 days. Water
      content and intact neurons were detected in the rats 3 days after ICH, and the
      neurological deficit scores were examined in the rats at 4, 24, 72, and 168 h
      after ICH. Apoptosis was evaluated via caspase-3 immunohistochemistry, Nissl
      staining, and TUNEL assay. We also examined the effect of GHK on the expression
      of related proteins in SH-SY5Y cells via Western blotting. The expression of miR
      339-5p was examined via real-time polymerase chain reaction analyses. GHK
      improved neurological deficits, reduced water content in the brain and inhibited
      neuronal apoptosis in ICH rats. It also prevented the apoptosis of SH-SY5Y cells
      with hemin treatment. Furthermore, GHK downregulated miR-339-5p expression, and
      overexpression of miR-339-5p partially reversed the anti-apoptotic effects of GHK
      in SH-SY5Y cells. Our findings suggest that the p38 MAPK pathway is involved in
      the GHK-induced downregulation of miR-339-5p, and that the miR-339-5p/VEGFA axis
      plays a role in preventing neuronal apoptosis following ICH injury. These
      findings indicate that GHK may represent a novel therapeutic strategy for ICH.

PMID- 30294254
TI  - Do Complexity Measures of Frontal EEG Distinguish Loss of Consciousness in
      Geriatric Patients Under Anesthesia?
AB  - While geriatric patients have a high likelihood of requiring anesthesia, they
      carry an increased risk for adverse cognitive outcomes from its use. Previous
      work suggests this could be mitigated by better intraoperative monitoring using
      indexes defined by several processed electroencephalogram (EEG) measures.
      Unfortunately, inconsistencies between patients and anesthetic agents in current
      analysis techniques have limited the adoption of EEG as standard of care. In
      attempts to identify new analyses that discriminate clinically-relevant
      anesthesia timepoints, we tested 1/f frequency scaling as well as measures of
      complexity from nonlinear dynamics. Specifically, we tested whether analyses that
      characterize time-delayed embeddings, correlation dimension (CD), phase-space
      geometric analysis, and multiscale entropy (MSE) capture loss-of-consciousness
      changes in EEG activity. We performed these analyses on EEG activity collected
      from a traditionally hard-to-monitor patient population: geriatric patients on
      beta-adrenergic blockade who were anesthetized using a combination of fentanyl
      and propofol. We compared these analyses to traditional frequency-derived
      measures to test how well they discriminated EEG states before and after loss of
      response to verbal stimuli. We found spectral changes similar to those reported
      previously during loss of response. We also found significant changes in 1/f
      frequency scaling. Additionally, we found that our phase-space geometric
      characterization of time-delayed embeddings showed significant differences before
      and after loss of response, as did measures of MSE. Our results suggest that our
      new spectral and complexity measures are capable of capturing subtle differences
      in EEG activity with anesthesia administration-differences which future work may
      reveal to improve geriatric patient monitoring.

PMID- 30294256
TI  - Andrographolide Alleviates Acute Brain Injury in a Rat Model of Traumatic Brain
      Injury: Possible Involvement of Inflammatory Signaling.
AB  - Neuroinflammation plays an important role in secondary injury after traumatic
      brain injury (TBI). Andrographolide (Andro), a diterpenoid lactone isolated from
      Andrographis paniculata, has been demonstrated to exhibit anti-inflammatory
      activity in neurodegenerative disorders. This study therefore aimed to
      investigate the potential neuroprotective effects of Andro after TBI and explore
      the underlying mechanisms. In our study, we used a weight-dropped model to induce
      TBI in Sprague-Dawley rats, the neurological deficits were assessed using
      modified neurological severity scores, Fluoro-Jade B (FJB) and terminal
      deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining were
      employed to examine neuronal degeneration and apoptosis after TBI,
      immunofluorescence was designed to investigate microglial activation.
      Quantitative Real-time PCR and ELISA were conducted to detect the expression
      levels of pro-inflammatory cytokines, Western blot was used to examine the
      expression level of proteins of relative signaling pathway. Our results showed
      that after Andro administration, the neurological deficit was attenuated, and the
      cerebral edema and apoptosis in brain tissues were also decreased following TBI.
      Both microglial activation and the expression of pro-inflammatory cytokines were
      significantly inhibited by Andro after TBI. Moreover, Andro inhibited NF-kappaB
      p65 subunit translocation and decreased the expression levels of phosphorylated
      extracellular signal regulated kinase (ERK) and p38 MAPK after TBI. Altogether,
      this study suggests that Andro could improve neurobehavioral function by
      inhibiting NF-kappaB and MAPK signaling pathway in TBI, which might provide a new
      approach for treating brain injury.

PMID- 30294257
TI  - The Association Between Genetic Variation in FOXP2 and Sensorimotor Control of
      Speech Production.
AB  - Significant advances have been made in understanding the role of auditory
      feedback in sensorimotor integration for speech production. The neurogenetic
      basis of this feedback-based control process, however, remains largely unknown.
      Mutations of FOXP2 gene in humans are associated with severe deficits in speech
      motor behavior. The present study examined the associations between a FOXP2
      common variant, rs6980093 (A/G), and the behavioral and event-related potential
      (ERP) responses to -50 and -200 cents pitch perturbations during vocal production
      in a sample of 133 Chinese adults. Behaviorally, the GG genotype was associated
      with significantly smaller vocal compensations for -200 cents perturbations
      relative to the AA and AG genotypes. Furthermore, both the AA and AG genotypes
      exhibited significant positive correlations between the degree of vocal
      compensation for -50 and -200 cents perturbations and the variability of normal
      voice fundamental frequency, whereas no such correlation existed for the GG
      genotype. At the cortical level, significantly larger P2 responses to -200 cents
      perturbations were associated with the GG genotype as compared to the AA and AG
      genotypes due to increased left-lateralized activity in the superior, middle, and
      inferior frontal gyrus, precentral gyrus, anterior cingulate cortex, middle
      temporal gyrus, and insula. The neurobehavioral responses to -50 cents
      perturbations, however, did not vary as a function of genotype. These findings
      present the first neurobehavioral evidence for an association between FOXP2
      genetic variant and auditory-motor integration for vocal pitch regulation. The
      differential effects of FOXP2 genotypes at rs6980093 may reflect their influences
      on the weighting of feedback and feedforward control of speech production.

PMID- 30294258
TI  - Negative Allosteric Modulators of mGlu7 Receptor as Putative Antipsychotic Drugs.
AB  - The data concerning antipsychotic-like activity of negative allosteric modulators
      (NAMs)/antagonists of mGlu7 receptors are limited. The only available ligands for
      this receptor are MMPIP and ADX71743. In the present studies, we used stable cell
      line expressing mGlu7 receptor and it was shown that both compounds dose
      dependently potentiated forskolin elevated cAMP concentration in the T-REx 293
      cells, showing their inverse agonist properties. Subsequently, pharmacokinetic
      studies were performed. Both compounds were given intraperitoneally (i.p.) at the
      dose of 10 mg/kg and reached Cmax 0.25-0.5 h after administration, and then they
      declined rapidly, ADX71743 being almost undetectable 2 h after administration,
      while the concentration of MMPIP was still observed, suggesting that the
      concentration of MMPIP was more stable. Finally, we investigated the role of both
      mGlu7 receptor NAMs in animal models of schizophrenia. Behavioral tests commonly
      used in antipsychotic drug discovery were conducted. Both tested compounds dose
      dependently inhibited MK-801-induced hyperactivity (MMPIP at 15 mg/kg; ADX at 5
      and 15 mg/kg) and DOI-induced head twitches (MMPIP at 5, 10, 15 mg/kg; ADX at
      2.5, 5, 10 mg/kg). Moreover, the same effects were noticed in novel object
      recognition test, where MMPIP (5, 10, 15 mg/kg) and ADX71743 (1, 5, 15 mg/kg)
      reversed MK-801-induced disturbances. In the social interaction test,
      antipsychotic activity was observed only for ADX71743 (5, 15 mg/kg). ADX71743 at
      the dose 2.5 mg/kg reversed MK-801-induced disruption in prepulse inhibition
      while MMPIP at 10 mg/kg reversed MK-801-induced disruption in spatial delayed
      alternation. The present studies showed that mGlu7 receptor may be considered as
      a putative target for antipsychotic drugs, though more studies are needed due to
      limited number of available ligands.

PMID- 30294260
TI  - Commentary: Multiscale Analysis of Independent Alzheimer's Cohorts Finds
      Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus.

PMID- 30294255
TI  - Pluripotent Stem Cell-Based Approaches to Explore and Treat Optic Neuropathies.
AB  - Sight is a major sense for human and visual impairment profoundly affects quality
      of life, especially retinal degenerative diseases which are the leading cause of
      irreversible blindness worldwide. As for other neurodegenerative disorders,
      almost all retinal dystrophies are characterized by the specific loss of one or
      two cell types, such as retinal ganglion cells, photoreceptor cells, or retinal
      pigmented epithelial cells. This feature is a critical point when dealing with
      cell replacement strategies considering that the preservation of other cell types
      and retinal circuitry is a prerequisite. Retinal ganglion cells are particularly
      vulnerable to degenerative process and glaucoma, the most common optic
      neuropathy, is a frequent retinal dystrophy. Cell replacement has been proposed
      as a potential approach to take on the challenge of visual restoration, but its
      application to optic neuropathies is particularly challenging. Many obstacles
      need to be overcome before any clinical application. Beyond their survival and
      differentiation, engrafted cells have to reconnect with both upstream synaptic
      retinal cell partners and specific targets in the brain. To date, reconnection of
      retinal ganglion cells with distal central targets appears unrealistic since
      central nervous system is refractory to regenerative processes. Significant
      progress on the understanding of molecular mechanisms that prevent central
      nervous system regeneration offer hope to overcome this obstacle in the future.
      At the same time, emergence of reprogramming of human somatic cells into
      pluripotent stem cells has facilitated both the generation of new source of cells
      with therapeutic potential and the development of innovative methods for the
      generation of transplantable cells. In this review, we discuss the feasibility of
      stem cell-based strategies applied to retinal ganglion cells and optic nerve
      impairment. We present the different strategies for the generation,
      characterization and the delivery of transplantable retinal ganglion cells
      derived from pluripotent stem cells. The relevance of pluripotent stem cell
      derived retinal organoid and retinal ganglion cells for disease modeling or drug
      screening will be also introduced in the context of optic neuropathies.

PMID- 30294259
TI  - Gadolinium Deposition in Brain: Current Scientific Evidence and Future
      Perspectives.
AB  - In the past 4 years, many publications described a concentration-dependent
      deposition of gadolinium in the brain both in adults and children, seen as high
      signal intensities in the globus pallidus and dentate nucleus on unenhanced T1
      weighted images. Postmortem human or animal studies have validated gadolinium
      deposition in these T1-hyperintensity areas, raising new concerns on the safety
      of gadolinium-based contrast agents (GBCAs). Residual gadolinium is deposited not
      only in brain, but also in extracranial tissues such as liver, skin, and bone.
      This review summarizes the current evidence on gadolinium deposition in the human
      and animal bodies, evaluates the effects of different types of GBCAs on the
      gadolinium deposition, introduces the possible entrance or clearance mechanism of
      the gadolinium and potential side effects that may be related to the gadolinium
      deposition on human or animals, and puts forward some suggestions for further
      research.

PMID- 30294262
TI  - Bessel Beam Illumination Reduces Random and Systematic Errors in Quantitative
      Functional Studies Using Light-Sheet Microscopy.
AB  - Light-sheet microscopy (LSM), in combination with intrinsically transparent
      zebrafish larvae, is a method of choice to observe brain function with high frame
      rates at cellular resolution. Inherently to LSM, however, residual opaque objects
      cause stripe artifacts, which obscure features of interest and, during functional
      imaging, modulate fluorescence variations related to neuronal activity. Here, we
      report how Bessel beams reduce streaking artifacts and produce high-fidelity
      quantitative data demonstrating a fivefold increase in sensitivity to calcium
      transients and a 20-fold increase in accuracy in the detection of activity
      correlations in functional imaging. Furthermore, using principal component
      analysis, we show that measurements obtained with Bessel beams are clean enough
      to reveal in one-shot experiments correlations that can not be averaged over
      trials after stimuli as is the case when studying spontaneous activity. Our
      results not only demonstrate the contamination of data by systematic and random
      errors through conventional Gaussian illumination and but,furthermore, quantify
      the increase in fidelity of such data when using Bessel beams.

PMID- 30294261
TI  - Sigma-1 Receptor-Modulated Neuroinflammation in Neurological Diseases.
AB  - A large body of evidence indicates that sigma-1 receptors (Sig-1R) are important
      drug targets for a number of neuropsychiatric disorders. Sig-1Rs are enriched in
      central nervous system (CNS). In addition to neurons, both cerebral microglia and
      astrocytes express Sig-1Rs. Activation of Sig-1Rs is known to elicit potent
      neuroprotective effects and promote neuronal survival via multiple mechanisms,
      including promoting mitochondrial functions, decreasing oxidative stress and
      regulating neuroimmnological functions. In this review article, we focus on the
      emerging role of Sig-1Rs in regulating neuroinflammation and discuss the recent
      advances on the Sig-1R-modulating neuroinflammation in the pathophysiology and
      therapy of neurodegenerative disorders.

PMID- 30294263
TI  - A Comparison of Machine Learning Classifiers for Energy-Efficient Implementation
      of Seizure Detection.
AB  - The closed-loop application of electrical stimulation via chronically implanted
      electrodes is a novel approach to stop seizures in patients with focal-onset
      epilepsy. To this end, an energy efficient seizure detector that can be
      implemented in an implantable device is of crucial importance. In this study, we
      first evaluated the performance of two machine learning algorithms (Random Forest
      classifier and support vector machine (SVM)) by using selected time and frequency
      domain features with a limited need of computational resources. Performance of
      the algorithms was further compared to a detection strategy implemented in an
      existing closed loop neurostimulation device for the treatment of epilepsy. The
      results show a superior performance of the Random Forest classifier compared to
      the SVM classifier and the reference approach. Next, we implemented the feature
      extraction and classification process of the Random Forest classifier on a
      microcontroller to evaluate the energy efficiency of this seizure detector. In
      conclusion, the feature set in combination with Random Forest classifier is an
      energy efficient hardware implementation that shows an improvement of detection
      sensitivity and specificity compared to the presently available closed-loop
      intervention in epilepsy while preserving a low detection delay.

PMID- 30294264
TI  - Precision and False Perceptual Inference.
AB  - Accurate perceptual inference fundamentally depends upon accurate beliefs about
      the reliability of sensory data. In this paper, we describe a Bayes optimal and
      biologically plausible scheme that refines these beliefs through a gradient
      descent on variational free energy. To illustrate this, we simulate belief
      updating during visual foraging and show that changes in estimated sensory
      precision (i.e., confidence in visual data) are highly sensitive to prior beliefs
      about the contents of a visual scene. In brief, confident prior beliefs induce an
      increase in estimated precision when consistent with sensory evidence, but a
      decrease when they conflict. Prior beliefs held with low confidence are rapidly
      updated to posterior beliefs, determined by sensory data. These induce much
      smaller changes in beliefs about sensory precision. We argue that pathologies of
      scene construction may be due to abnormal priors, and show that these can induce
      a reduction in estimated sensory precision. Having previously associated this
      precision with cholinergic signaling, we note that several neurodegenerative
      conditions are associated with visual disturbances and cholinergic deficits;
      notably, the synucleinopathies. On relating the message passing in our model to
      the functional anatomy of the ventral visual stream, we find that simulated
      neuronal loss in temporal lobe regions induces confident, inaccurate, empirical
      prior beliefs at lower levels in the visual hierarchy. This provides a plausible,
      if speculative, computational mechanism for the loss of cholinergic signaling and
      the visual disturbances associated with temporal lobe Lewy body pathology. This
      may be seen as an illustration of the sorts of hypotheses that may be expressed
      within this computational framework.

PMID- 30294265
TI  - When Does Oxytocin Affect Human Memory Encoding? The Role of Social Context and
      Individual Attachment Style.
AB  - The neuropeptide oxytocin plays an essential role in regulating social behavior
      and has been implicated in a variety of human cognitive processes in the social
      domain, including memory processes. The present study investigates the influence
      of oxytocin on human memory encoding, taking into account social context and
      personality, which have previously been neglected as moderators for how oxytocin
      affects memory encoding. To examine the role of social context of encoding, we
      employed an established experimental paradigm in which participants perform a
      word-categorization task in either a joint (social) or individual (non-social)
      setting. To investigate the role of socially relevant personality factors,
      participants' adult attachment style (AAS) was assessed. Previous research has
      identified attachment style as a potent moderator of oxytocin effects in the
      social-cognitive domain, but here we investigated for the first time its role in
      memory encoding. Participants were invited in pairs and received either placebo
      or oxytocin intranasally. Forty-five minutes later, they were instructed to react
      to different word categories within a list of successively presented words. This
      task was performed individually in the non-social condition and simultaneously
      with the partner in the social condition. After a 24-h delay, memory for all
      words was tested individually in a surprise recognition memory test. Oxytocin
      effects on memory accuracy depended on participants' AAS. Specifically, oxytocin
      positively affected memory for participants who scored low on attachment
      dependence (who find dependence on others uncomfortable), but negatively affected
      memory for high scorers (who are comfortable depending on others). Oxytocin
      effects were not moderated by social vs. non-social context at encoding, and we
      discuss reasons for this outcome. Regardless of encoding condition or
      personality, oxytocin led to more liberal responding in the recognition memory
      test, which was also reflected in significantly higher false alarm rates (FARs)
      and a trend towards higher hit rates (HRs) compared to placebo. Overall, our
      results are consistent with an interactionist view on oxytocin effects on human
      cognitive functioning. Future research should further examine how oxytocin
      affects response biases via previous encoding and the ways in which biological
      dispositions linked to attachment style affect the process of memory encoding.

PMID- 30294267
TI  - Out of the Loop, in Your Bubble: Mind Wandering Is Independent From Automation
      Reliability, but Influences Task Engagement.
AB  - This study examined the influence of automation reliability on task-unrelated
      mind wandering (MW) frequency and the impact of MW on task engagement. Automated
      environment features make it particularly prone to increase MW frequency. Through
      mechanisms like complacency or agency, automating a task could increase MW
      frequency for the operator. For safety-critical industries, the lower perception
      and degraded stimuli processing associated with MW, summarized by the term
      "decoupling hypothesis," are particularly concerning. Sixteen participants
      supervised an autopilot avoiding obstacles with two levels of reliability. Each
      condition lasted 45 min. We recorded thoughts as either pertaining to being
      focused, task-related MW or task-unrelated MW. We also recorded perceived mental
      demand, trust regarding the autopilot and oculometric measures. Based on
      questionnaire results, our protocol succeeded in inducing more mental demand and
      lower trust when the automation was unreliable. Attentional states were not
      correlated, nor did it influence trust in the system reliability. On the
      contrary, mental demand ratings and pupil diameter were lower during both task
      related and task-unrelated MW, compared to those during the focus attentional
      state. This shows that perceptual decoupling also affects the engagement of
      operators in automated environments, which may dramatically lower their ability
      to supervise automation efficiently. This research informs human-automation
      designers to consider operator engagement when creating automated systems.

PMID- 30294266
TI  - Cognitive Fatigue, Sleep and Cortical Activity in Multiple Sclerosis Disease. A
      Behavioral, Polysomnographic and Functional Near-Infrared Spectroscopy
      Investigation.
AB  - Patients with multiple sclerosis (MS) disease frequently experience fatigue as
      their most debilitating symptom. Fatigue in MS partially refers to a cognitive
      component, cognitive fatigue (CF), characterized by a faster and stronger than
      usual development of the subjective feeling of exhaustion that follows sustained
      cognitive demands. The feeling of CF might result from supplementary task-related
      brain activity following MS-related demyelination and neurodegeneration. Besides,
      CF in MS disease might also stem from disrupted sleep. The present study
      investigated the association between the triggering of CF, task-related brain
      activity and sleep features. In a counterbalance mixed design, 10 patients with
      MS and 11 healthy controls were exposed twice for 16 min to a CF-inducing dual
      working memory updating task (TloadDback) under low or high cognitive demands
      conditions, counterbalanced. Considering known inter-individual differences and
      potential cognitive deficits in MS, the maximal cognitive load of the task was
      individually adapted to each participant's own upper limits. During the
      experimental sessions, cortical brain activity was measured using near-infrared
      spectroscopy (NIRS) during the CF-induction task, and in a resting state
      immediately before and after. Ambulatory polysomnography recordings were obtained
      on the nights preceding experimental sessions. When cognitive load was
      individually adapted to their processing capabilities, patients with MS exhibited
      similar than healthy controls levels of subjectively perceived CF, evolution of
      performance during the task, and brain activity patterns. Linear mixed models
      indicate a negative association between oxygenation level changes in the
      dorsolateral prefrontal cortex (DLPFC) and the triggering of subjective CF in
      patients with MS only. Longer total sleep time was also associated with higher CF
      in MS patients. These results suggest that controlling for cognitive load between
      individuals with and without MS results in a similar task-related development of
      subjective CF. Besides comparable performance and cortical brain activity between
      groups, mixed model analyses suggest a possible association between CF, DLPFC
      activity and sleep duration in MS disease.

PMID- 30294268
TI  - A Computational Model of Deep-Brain Stimulation for Acquired Dystonia in
      Children.
AB  - The mechanism by which deep brain stimulation (DBS) improves dystonia is not
      understood, partly heterogeneity of the underlying disorders leads to differing
      effects of stimulation in different locations. Similarity between the effects of
      DBS and the effects of lesions has led to biophysical models of blockade or
      reduced transmission of involuntary activity in individual cells in the pathways
      responsible for dystonia. Here, we expand these theories by modeling the effect
      of DBS on populations of neurons. We emphasize the important observation that the
      DBS signal itself causes surprisingly few side effects and does not normally
      appear in the electromyographic signal. We hypothesize that, at the population
      level, massively synchronous rhythmic firing caused by DBS is only poorly
      transmitted through downstream populations. However, the high frequency of
      stimulation overwhelms incoming dystonic activity, thereby substituting an
      ineffectively transmitted exogenous signal for the endogenous abnormal signal.
      Changes in sensitivity can occur not only at the site of stimulation, but also at
      downstream sites due to synaptic and homeostatic plasticity mechanisms. The
      mechanism is predicted to depend strongly on the stimulation frequency. We
      provide preliminary data from simultaneous multichannel recordings in basal
      ganglia and thalamus in children with secondary dystonia. We also provide
      illustrative simulations of the effect of stimulation frequency on the
      transmission of the DBS pulses through sequential populations of neurons in the
      dystonia pathway. Our experimental results and model provide a new hypothesis and
      computational framework consistent with the clinical features of DBS in childhood
      acquired dystonia.

PMID- 30294269
TI  - Accurate Reconstruction of Image Stimuli From Human Functional Magnetic Resonance
      Imaging Based on the Decoding Model With Capsule Network Architecture.
AB  - In neuroscience, all kinds of computation models were designed to answer the open
      question of how sensory stimuli are encoded by neurons and conversely, how
      sensory stimuli can be decoded from neuronal activities. Especially, functional
      Magnetic Resonance Imaging (fMRI) studies have made many great achievements with
      the rapid development of deep network computation. However, comparing with the
      goal of decoding orientation, position and object category from human fMRI in
      visual cortex, accurate reconstruction of image stimuli is a still challenging
      work. Current prevailing methods were composed of two independent steps, (1)
      decoding intermediate features from human fMRI and (2) reconstruction using the
      decoded intermediate features. The new concept of 'capsule' and 'capsule' based
      neural network were proposed recently. The 'capsule' represented a kind of
      structure containing a group of neurons to perform better feature representation.
      Especially, the high-level capsule's features in the capsule network (CapsNet)
      contains various features of image stimuli such as semantic class, orientation,
      location, scale and so on, and these features can better represent the processed
      information inherited in the fMRI data collected in visual cortex. In this paper,
      a novel CapsNet architecture based visual reconstruction (CNAVR) computation
      model is developed to reconstruct image stimuli from human fMRI. The CNAVR is
      composed of linear encoding computation from capsule's features to fMRI data and
      inverse reconstruction computation. In the first part, we trained the CapsNet
      model to obtain the non-linear mappings from images to high-level capsule's
      features, and from high-level capsule's features to images again in an end-to-end
      manner. In the second part, we trained the non-linear mapping from fMRI data of
      selected voxels to high-level capsule's features. For a new image stimulus, we
      can use the method to predict the corresponding high-level capsule's features
      using fMRI data, and reconstruct image stimuli with the trained reconstruction
      part in the CapsNet. We evaluated the proposed CNAVR method on the open dataset
      of handwritten digital images, and exceeded about 10% than the accuracy of all
      existing state-of-the-art methods on the structural similarity index (SSIM). In
      addition, we explained the selected voxels in specific interpretable image
      features to prove the effectivity and generalization of the CNAVR method.

PMID- 30294270
TI  - Isoliquiritigenin Inhibits Cigarette Smoke-Induced COPD by Attenuating
      Inflammation and Oxidative Stress via the Regulation of the Nrf2 and NF-kappaB
      Signaling Pathways.
AB  - Chronic obstructive pulmonary disease (COPD) is the major leading cause of
      disease with high-mortality worldwide. Cigarette smoke (CS) is a major factor for
      COPD. CS causes chronic inflammation and oxidative stress, which contributes to
      lung dysfunction in COPD. Isoliquiritigenin (ILG), a natural flavonoid derived
      from the root of liquorice, has been reported to possess antiinflammatory and
      antioxidant activity. In the present study, we tested the mechanism and
      protective effects of ILG on CS-induced COPD. Mice were exposed to CS for 2 h
      twice a day for 4 weeks. ILG was given orally 1 h before CS exposure twice a day
      for 4 weeks. The bronchial alveolar lavage fluid was collected to test the levels
      of inflammatory cytokines and the number of inflammatory cells. The lung tissues
      were obtained to evaluate the pathological changes, lung edema, myeloperoxidase
      (MPO) activity, malondialdehyde (MDA) level, as well as the expression of the
      nuclear factor-erythroid 2 (Nrf2) and nuclear factor kappaB (NF-kappaB) signaling
      pathways. The results showed that ILG reduced the infiltration of inflammatory
      cells and the production of inflammatory cytokines. ILG also reversed CS-induced
      lung pathological injuries, wet/dry ratio, MPO activity, and MDA level. Further
      research also showed that ILG dose-dependently up-regulated the expression of
      Nrf2 and down-regulated the expression of NF-kappaB signaling pathways induced by
      CS. In conclusion, ILG protected against CS-induced COPD by inhibiting
      inflammatory and oxidative stress via the regulation of the Nrf2 and NF-kappaB
      signaling pathways.

PMID- 30294271
TI  - Identification of Antioxidant Proteins With Deep Learning From Sequence
      Information.
AB  - Antioxidant proteins have been found closely linked to disease control for its
      ability to eliminate excess free radicals. Because of its medicinal value, the
      study of identifying antioxidant proteins is on the upsurge. Many machine
      learning classifiers have performed poorly owing to the nonlinear and unbalanced
      nature of biological data. Recently, deep learning techniques showed advantages
      over many state-of-the-art machine learning methods in various fields. In this
      study, a deep learning based classifier was proposed to identify antioxidant
      proteins based on mixed g-gap dipeptide composition feature vector. The
      classifier employed deep autoencoder to extract nonlinear representation from raw
      input. The t-Distributed Stochastic Neighbor Embedding (t-SNE) was used for
      dimensionality reduction. Support vector machine was finally performed for
      classification. The classifier achieved F 1 score of 0.8842 and MCC of 0.7409 in
      10-fold cross validation. Experimental results show that our proposed method
      outperformed the traditional machine learning methods and could be a promising
      tool for antioxidant protein identification. For the convenience of others'
      scientific research, we have developed a user-friendly web server called IDAod
      for antioxidant protein identification, which can be accessed freely at
      http://bigroup.uestc.edu.cn/IDAod/.

PMID- 30294273
TI  - The Pathways for Layered Double Hydroxide Nanoparticles to Enhance Antigen
      (Cross)-Presentation on Immune Cells as Adjuvants for Protein Vaccines.
AB  - Nanoparticles (NPs) are intensively investigated as adjuvants in new generation
      vaccines, while how these NPs promote the immune responses has not been well
      understood. In this research, we have tried to elucidate the possible pathways
      for layered double hydroxide (LDH) NPs to provoke immune responses. As previously
      reported, LDH NPs efficiently deliver antigens to antigen presenting cells
      (APCs). In this research, we have found that these internalized LDH NPs are not
      released by these APCs within 8 h. We have for the first time found that
      macrophage cells exchange the internalized LDH NPs with other surrounding ones,
      which may promote immune responses in an additional way. Moreover, the
      internalized LDH-antigen NPs significantly facilitate the maturation of immature
      DCs and enhance cross-presentation of epitope/MHC class I complexes on the DC
      surface. This research would help understand the NP adjuvant mechanism and
      further assist the design of new specific NPs as more efficient nano-adjuvants.

PMID- 30294274
TI  - Editorial: Drug Repositioning: Current Advances and Future Perspectives.

PMID- 30294275
TI  - Comparative Price Analysis of Biological Products for Treatment of Rheumatoid
      Arthritis.
AB  - Biological products for treatment of rheumatoid arthritis usually are cost
      effective for healthcare systems in Europe, but they are huge financial burden
      due to the high number of patients and the significant budget impact. The
      expected saving from introduction on the market of biosimilars are significant
      and are linked to better access and affordability. The aim of this study was to
      conduct comparative price analysis of biological products for rheumatoid
      arthritis therapy among seventeen EU countries. The point of view is that of the
      Bulgarian pricing and reimbursement system and the chosen countries are those
      from external reference basket for prices comparison at manufacturing level. All
      authorized biological products by EMA with therapeutic indication rheumatoid
      arthritis were selected. The access for treatment is evaluated as the
      availability of the product on the market and the prices level. We assessed the
      availability of all trade names in the price lists of the observed countries. The
      prices data was obtained from the official web pages of the responsible
      institutions up to date December 2017. The results show that four out of all six
      INNs have authorized biosimilars in EMA. Despite its earlier authorization
      biosimilar adalimumab is not present in any of the price lists of countries. From
      all eighteen countries only in Lithuania and Estonia there were no published
      prices of any of the selected medicinal products. Countries with higher number of
      biosimilar prices are Spain and France. Differences in manufacturers' prices of
      reference biological products in selected countries in comparison with the lowest
      manufacturer price are higher with 22 to 69% while the retail prices between 62
      and 95%. Differences are mostly notable for rituximab, and less notable for
      tocilizumab. Manufacturers' and retail prices of biosimilar products were
      established only for three INNs (etanercept, rituximab, and infliximab).
      Manufacturers' prices differ between 26 and 75%, while retail prices differ
      between 40 and 92% for biosimilars. Comparison of the differences between
      manufacturer prices of reference biological product and biosimilars shows 36%
      difference for etanercept, 39% for rituximab, and 31% for infliximab, while at
      retail level the differences are 11, 86, and 143%, respectively. The limitation
      of the study is that the prices are the official ones without discounts due to
      confidentiality and the real prices may be lower. The second limitation is that
      the methodology for pricing differs in the countries and this could also
      influence the prices on both levels (manufacturer and retail). Introduction of
      biosimilars on the national markets led to significant decrease in reimbursed
      prices paid by public funds and thus might benefit the patients' access to
      biological therapy. The decrease of prices after biosimilars entrance on the
      market is not as notable as for commodity generics.

PMID- 30294272
TI  - Prognostic Factors for Checkpoint Inhibitor Based Immunotherapy: An Update With
      New Evidences.
AB  - Checkpoint inhibitor (CPI) based immunotherapy (i.e., anit-CTLA-4/PD-1/PD-L1
      antibodies) can effectively prolong overall survival of patients across several
      cancer types at the advanced stage. However, only part of patients experience
      objective responses from such treatments, illustrating large individual
      differences in terms of both efficacy and adverse drug reactions. Through the
      observation on a series of CPI based clinical trials in independent patient
      cohorts, associations of multiple clinical and molecular characteristics with CPI
      response rate have been determined, including microenvironment, genomic
      alterations of the cancer cells, and even gut microbiota. A broad interest has
      been drawn to the question whether and how these prognostic factors can be used
      as biomarkers for optimal usage of CPIs in precision immunotherapy. Therefore, we
      reviewed the candidate prognostic factors identified by multiple trials and the
      experimental investigations, especially those reported in the recent 2 years, and
      described the possibilities and problems of them in routine clinical usage of
      cancer treatment as biomarkers.

PMID- 30294276
TI  - Common Traits Spark the Mitophagy/Xenophagy Interplay.
AB  - Selective autophagy contributes to the wellbeing of eukaryotic cells by recycling
      cellular components, disposing damaged organelles, and removing pathogens,
      amongst others. Both the quality control process of selective mitochondrial
      autophagy (Mitophagy) and the defensive process of intracellular pathogen
      engulfment (Xenophagy) are facilitated via protein assemblies which have shared
      molecules, a prime example being the Tank-Binding Kinase 1 (TBK1). TBK1 plays a
      central role in the immunity response driven by Xenophagy and was recently shown
      to be an amplifying mechanism in Mitophagy, bring to attention the potential
      cross talk between the two processes. Here we draw parallels between Xenophagy
      and Mitophagy, speculating on the inhibitory mechanisms of specific proteins
      (e.g., the 18 kDa protein TSPO), how the preferential sequestering toward one of
      the two pathways may undermine the other, and in this way impair cellular
      response to pathogens and cellular immunity. We believe that an in depth
      understanding of the commonalities may present an opportunity to design novel
      therapeutic strategies targeted at both the autonomous and non-autonomous
      processes of selective autophagy.

PMID- 30294277
TI  - Characterization of Simultaneous Pressure Waves as Biomarkers for Colonic
      Motility Assessed by High-Resolution Colonic Manometry.
AB  - Simultaneous pressure waves (SPWs) in manometry recordings of the human colon
      have been associated with gas expulsion. Our hypothesis was that the SPW might be
      a critical component of most colonic motor functions, and hence might act as a
      biomarker for healthy colon motility. To that end, we performed high-resolution
      colonic manometry (HRCM), for the first time using an 84-sensor (1 cm spaced)
      water-perfused catheter, in 17 healthy volunteers. Intraluminal pressure patterns
      were recorded during baseline, proximal and rectal balloon distention, after a
      meal and following proximal and rectal luminal bisacodyl administration.
      Quantification was performed using software, based on Image J, developed during
      this study. Gas expulsion was always associated with SPWs, furthermore, SPWs were
      associated with water or balloon expulsion. SPWs were prominently emerging at the
      termination of proximal high amplitude propagating pressure waves (HAPWs); we
      termed this motor pattern HAPW-SPWs; hence, SPWs were often not a pan-colonic
      event. SPWs and HAPW-SPWs were observed at baseline with SPW amplitudes of 12.0
      +/- 8.5 mmHg and 20.2 +/- 7.2 mmHg respectively. The SPW occurrence and amplitude
      significantly increased in response to meal, balloon distention and luminal
      bisacodyl, associated with 50.3% anal sphincter relaxation at baseline, which
      significantly increased to 59.0% after a meal, and 69.1% after bisacodyl. Often,
      full relaxation was achieved. The SPWs associated with gas expulsion had a
      significantly higher amplitude compared to SPWs without gas expulsion. SPWs could
      be seen to consist of clusters of high frequency pressure waves, likely
      associated with a cluster of fast propagating, circular muscle contractions. SPWs
      were occasionally observed in a highly rhythmic pattern at 1.8 +/- 1.2
      cycles/min. Unlike HAPWs, the SPWs did not obliterate haustral boundaries thereby
      explaining how gas can be expelled while solid content can remain restrained by
      the haustral boundaries. In conclusion, the SPW may become a biomarker for normal
      gas transit, the gastrocolonic reflex and extrinsic neural reflexes. The SPW
      assessment reveals coordination of activities in the colon, rectum and anal
      sphincters. SPWs may become of diagnostic value in patients with colonic
      dysmotility.

PMID- 30294278
TI  - Cell-Free Circulating Nucleic Acids as Early Biomarkers for NAFLD and NAFLD
      Associated Disorders.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the worldwide most common cause of
      chronic liver pathology, which prevalence strongly correlates with the increasing
      incidence of diabetes, obesity and metabolic syndrome in the general population.
      Simple steatosis, the earliest NAFLD stage, usually remains asymptomatic, and
      appropriate changes in the lifestyle, as well as the diet, can reverse the
      affected liver into the healthy state. The potential of simple steatosis to
      progress into severe fibrotic stages and to facilitate carcinogenesis
      necessitates timely NAFLD detection and risk stratification in community-based
      healthcare settings. Since their initial discovery a decade ago, extracellular
      circulating miRNAs have been found in all human biological fluids including blood
      and shown to hold great promises as non-invasive biomarkers. Normally,
      intracellular miRNAs participate in the regulation of gene expression, but once
      released by dying/dead cells they remain highly stable in the extracellular
      environment for prolonged periods. Therefore, circulating miRNA profiles can
      reflect the ongoing pathogenic processes in body's tissues and organs, and enable
      highly sensitive non-invasive diagnosis of multiple disorders. A non-urgent
      character of the NAFLD-related decision-making justifies the use of chronic liver
      diseases as an excellent test case for examining the practical utility of
      circulating miRNAs as biomarkers for longitudinal monitoring of human health. In
      this review, we summarize the state-of-the-art in the field of early diagnosis of
      NAFLD using circulating blood miRNAs, and stress the necessity of additional
      experimental validation of their diagnostic potential. We further emphasize on
      the potential diagnostics promises of other cell-free RNA species found in human
      biological fluids.

PMID- 30294280
TI  - Investigation of the Syncytial Nature of Detrusor Smooth Muscle as a Determinant
      of Action Potential Shape.
AB  - Unlike most excitable cells, certain syncytial smooth muscle cells are known to
      exhibit spontaneous action potentials of varying shapes and sizes. These
      differences in shape are observed even in electrophysiological recordings
      obtained from a single cell. The origin and physiological relevance of this
      phenomenon are currently unclear. The study presented here aims to test the
      hypothesis that the syncytial nature of the detrusor smooth muscle tissue
      contributes to the variations in the action potential profile by influencing the
      superposition of the passive and active signals. Data extracted from experimental
      recordings have been compared with those obtained through simulations. The
      feature correlation studies on action potentials obtained from the experimental
      recordings suggest the underlying presence of passive signals, called spontaneous
      excitatory junction potentials (sEJPs). Through simulations, we are able to
      demonstrate that the syncytial organization of the cells, and the variable
      superposition of the sEJPs with the "native action potential", contribute to the
      diversity in the action potential profiles exhibited. It could also be inferred
      that the fraction of the propagated action potentials is very low in the
      detrusor. It is proposed that objective measurements of spontaneous action
      potential profiles can lead to a better understanding of bladder physiology and
      pathology.

PMID- 30294279
TI  - Pathogenesis and Treatment Options of Cancer Related Anemia: Perspective for a
      Targeted Mechanism-Based Approach.
AB  - Cancer-related anemia (CRA) is a common sign occurring in more than 30% of cancer
      patients at diagnosis before the initiation of antineoplastic therapy. CRA has a
      relevant influence on survival, disease progression, treatment efficacy, and the
      patients' quality of life. It is more often detected in patients with advanced
      stage disease, where it represents a specific symptom of the neoplastic disease,
      as a consequence of chronic inflammation. In fact, CRA is characterized by
      biological and hematologic features that resemble those described in anemia
      associated to chronic inflammatory disease. Proinflammatory cytokine, mainly IL
      6, which are released by both tumor and immune cells, play a pivotal action in
      CRA etiopathogenesis: they promote alterations in erythroid progenitor
      proliferation, erythropoietin (EPO) production, survival of circulating
      erythrocytes, iron balance, redox status, and energy metabolism, all of which can
      lead to anemia. The discovery of hepcidin allowed a greater knowledge of the
      relationships between immune cells, iron metabolism, and anemia in chronic
      inflammatory diseases. Additionally, chronic inflammation influences a
      compromised nutritional status, which in turn might induce or contribute to CRA.
      In the present review we examine the multifactorial pathogenesis of CRA
      discussing the main and novel mechanisms by which immune, nutritional, and
      metabolic components affect its onset and severity. Moreover, we analyze the
      status of the art and the perspective for the treatment of CRA. Notably, despite
      the high incidence and clinical relevance of CRA, controlled clinical studies
      testing the most appropriate treatment for CRA are scarce, and its management in
      clinical practice remains challenging. The present review may be useful to
      indicate the development of an effective approach based on a detailed assessment
      of all factors potentially involved in the pathogenesis of CRA. This mechanism
      based approach is essential for clinicians to plan a safe, targeted, and
      successful therapy, thereby promoting a relevant amelioration of patients'
      quality of life.

PMID- 30294281
TI  - Validation and Opportunities of Electrocardiographic Imaging: From Technical
      Achievements to Clinical Applications.
AB  - Electrocardiographic imaging (ECGI) reconstructs the electrical activity of the
      heart from a dense array of body-surface electrocardiograms and a patient
      specific heart-torso geometry. Depending on how it is formulated, ECGI allows the
      reconstruction of the activation and recovery sequence of the heart, the origin
      of premature beats or tachycardia, the anchors/hotspots of re-entrant arrhythmias
      and other electrophysiological quantities of interest. Importantly, these
      quantities are directly and non-invasively reconstructed in a digitized model of
      the patient's three-dimensional heart, which has led to clinical interest in
      ECGI's ability to personalize diagnosis and guide therapy. Despite considerable
      development over the last decades, validation of ECGI is challenging. Firstly,
      results depend considerably on implementation choices, which are necessary to
      deal with ECGI's ill-posed character. Secondly, it is challenging to obtain
      (invasive) ground truth data of high quality. In this review, we discuss the
      current status of ECGI validation as well as the major challenges remaining for
      complete adoption of ECGI in clinical practice. Specifically, showing clinical
      benefit is essential for the adoption of ECGI. Such benefit may lie in patient
      outcome improvement, workflow improvement, or cost reduction. Future studies
      should focus on these aspects to achieve broad adoption of ECGI, but only after
      the technical challenges have been solved for that specific
      application/pathology. We propose 'best' practices for technical validation and
      highlight collaborative efforts recently organized in this field. Continued
      interaction between engineers, basic scientists, and physicians remains essential
      to find a hybrid between technical achievements, pathological mechanisms
      insights, and clinical benefit, to evolve this powerful technique toward a useful
      role in clinical practice.

PMID- 30294284
TI  - One Year of Yoga Training Alters Ghrelin Axis in Centrally Obese Adults With
      Metabolic Syndrome.
AB  - Introduction: Metabolic syndrome (MetS) is a multiplex cardiometabolic
      manifestation associated with type 2 diabetes mellitus and cardiovascular
      diseases. Yoga training has been shown to alleviate MetS. Recently, circulatory
      ghrelin profile was demonstrated to be associated with MetS. This study examined
      the effects of 1 year of yoga training on beta-cell function and insulin
      resistance, and the involvement of metabolic peptides, including unacylated
      ghrelin (UnAG), acylated ghrelin (AG), obestatin, growth hormone (GH), and
      insulin, in the beneficial effects of yoga training in centrally obese adults
      with MetS. Methods: This was a follow up study, in which data of risk factors of
      MetS, physical performance tests [resting heart rate (HR), chair stand test (CS),
      chair sit and reach test (CSR), back scratch test (BS), and single leg stand
      tests (SLS)] and serum samples of 79 centrally obese MetS subjects aged 58 +/- 8
      years (39 subjects received 1-year yoga training and 40 subjects received no
      training) were retrieved for analyses. beta-cell function and insulin resistance
      were examined by Homeostasis Model Assessment (HOMA). Circulating levels of UnAG,
      AG, obestatin, GH, and insulin were determined by enzyme-linked immunosorbent
      assay using fasting serum samples. Generalized estimating equation analysis and
      Mann-Whitney U-test were used to detect statistically significant differences
      between groups. Results: Waist circumference (WC) was significantly decreased
      after yoga intervention (control: +2%; yoga: -4%). Significant improvements in HR
      (control: +2%; yoga: -5%), CS (control: -1%; yoga: +24%), CSR left (control:
      worsen by 0.90 cm; yoga: improved by 4.21 cm), CSR right (control: worsen by 0.75
      cm; yoga: improved by 4.28 cm), right side of BS (control: improved by 0.19 cm;
      yoga: improved by 4.31 cm), SLS left (control: -10%; yoga: +86%), and SLS right
      (control: -6%; yoga: +47%) were observed after 1-year yoga training. No
      significant difference was found between the two groups in insulin, HOMA indices,
      and disposition index. Yoga training significantly increased circulating GH
      (control: -3%; yoga: +22%), total circulating ghrelin (control: -26%; yoga:
      +13%), and UnAG (control: -27%; yoga: +14%), whereas decreased AG (control: -7%;
      yoga: -33%) and obestatin (control: +24%; yoga: -29%). Conclusion: One-year of
      yoga training modulated total ghrelin, UnAG, AG, obestatin, and GH while exerting
      beneficial effects on physical functions and central obesity in adults with MetS.
      The beneficial effects of yoga may be associated with the alteration of ghrelin
      gene product and GH.

PMID- 30294283
TI  - RBPs Play Important Roles in Vascular Endothelial Dysfunction Under Diabetic
      Conditions.
AB  - Diabetes is one of the major health care problems worldwide leading to huge
      suffering and burden to patients and society. Diabetes is also considered as a
      cardiovascular disorder because of the correlation between diabetes and an
      increased incidence of cardiovascular disease. Vascular endothelial cell
      dysfunction is a major mediator of diabetic vascular complications. It has been
      established that diabetes contributes to significant alteration of the gene
      expression profile of vascular endothelial cells. Post-transcriptional regulation
      by RNA binding proteins (RBPs) plays an important role in the alteration of gene
      expression profile under diabetic conditions. The review focuses on the roles and
      mechanisms of critical RBPs toward diabetic vascular endothelial dysfunction.
      Deeper understanding of the post- transcriptional regulation by RBPs could lead
      to new therapeutic strategies against diabetic manifestation in the future.

PMID- 30294285
TI  - Current Perspectives on Role of MSC in Renal Pathophysiology.
AB  - In the course of the development and worsening of kidney disease, the treatments
      available are expensive and may cause adverse effects such as immune rejection,
      inadequate renal resources, or post-operative complications. Therefore, there is
      an urgent to develop more effective treatments. The advent of mesenchymal stem
      cells (MSCs) represents a new direction in this context. The current use of MSCs
      for the treatment of kidney disease has mostly involved experimental studies on
      animals and only a few clinical trials have been conducted. This review focused
      on the mechanisms of MSC involvement from different sources in the improvement of
      renal pathophysiology in recent years. These mechanisms include homing to damaged
      kidney tissue, and differentiating into or fusing with the innate cells of the
      kidney. The paracrine or endocrine action through secreting protective cytokines
      and/or releasing microvesicle from MSCs also plays a critical role in
      amelioration of kidney disease. With modern engineering technology like microRNA
      delivery and a combinational therapy approach such as reduction of renal fibrosis
      in obstructive nephropathy with MSCs and serelaxin, MSC may make great
      contribution to the improvement of renal pathophysiology. However, the
      therapeutic effects of MSC are still controversial and several problems remain
      unsolved. While it is too early to state that MSCs are useful for the treatment
      of renal diseases in clinic, it is thought that solutions to the existing
      problems will enable effective modulation of the biological characteristics of
      MSCs, thereby providing new and effective approaches for the treatment of renal
      diseases.

PMID- 30294282
TI  - Membrane Proteins Mediating Reception and Transduction in Chemosensory Neurons in
      Mosquitoes.
AB  - Mosquitoes use chemical cues to modulate important behaviors such as feeding,
      mating, and egg laying. The primary chemosensory organs comprising the paired
      antennae, maxillary palps and labial palps are adorned with porous sensilla that
      house primary sensory neurons. Dendrites of these neurons provide an interface
      between the chemical environment and higher order neuronal processing. Diverse
      proteins located on outer membranes interact with chemicals, ions, and soluble
      proteins outside the cell and within the lumen of sensilla. Here, we review the
      repertoire of chemosensory receptors and other membrane proteins involved in
      transduction and discuss the outlook for their functional characterization. We
      also provide a brief overview of select ion channels, their role in mammalian
      taste, and potential involvement in mosquito taste. These chemosensory proteins
      represent targets for the disruption of harmful biting behavior and disease
      transmission by mosquito vectors.

PMID- 30294286
TI  - Dose Reduction/Discontinuation of Antipsychotic Drugs in Psychosis; Effect on
      Cognition and Functional Outcomes.
AB  - Backgrounds: There is a debate regarding the optimal timing of discontinuation of
      antipsychotic drugs in patients with first episode psychosis (FEP) or
      schizophrenia. We aimed to provide a review of the literature on which strategy
      (medication maintenance vs. dose reduction/discontinuation) is more likely to
      maximize outcomes, such as cognition and social function. Methods: Using PubMed,
      the Cochrane Library and systematic reviews, articles published between 2007 and
      2018 were reviewed, which investigated the effect of dose
      reduction/discontinuation vs. maintenance treatment on measures of cognition
      and/or social function in FEP and schizophrenia. Results: Six studies were
      identified; 2 studies reported on cognition while 4 studies concern social
      function. All studies except one reported that improvement of functional outcomes
      in remitted patients with FEP or schizophrenia allocated to a dose
      reduction/discontinuation arm was equal to or better than that in patients for
      whom medication doses were maintained. One trial of social function with a 1-year
      follow-up period found a greater improvement in the medication maintenance group,
      while no group difference was observed with 3-year and 10-year follow-up periods.
      On the other hand, a 7-year follow-up study found a superiority for the dose
      reduction/discontinuation regimen in terms of social outcome. Two studies on
      cognition with a short follow-up period reported a greater improvement for the
      dose reduction/discontinuation group. Conclusions: Information on cognition and
      social function has been relatively sparse. These measures of functional outcome
      should be considered in deciding which strategy of antipsychotic treatments is
      beneficial in individual cases with FEP or schizophrenia.

PMID- 30294287
TI  - Creative Arts-Based Therapies for Stroke Survivors: A Qualitative Systematic
      Review.
AB  - Background: Stroke is a life-threating cerebrovascular disease. Without proper
      and immediate treatment, it can cause long-term disabilities and even death.
      While current rehabilitation focuses on functional needs, it does not fully
      address the psychosocial issues. Creative arts-based therapies, however, may have
      the potential to be of assistance. Methods: A systematic review was conducted to
      synthesize the qualitative findings of the stroke survivors' positive and
      negative experiences in participating in creative arts-based therapies. A
      systematic literature search was conducted across diverse databases. A thematic
      synthesis was adopted to analyze the results from different qualitative studies
      and mix-method studies. Results: Among the 367 studies extracted from various
      databases, 11 studies met the inclusion criteria and were of acceptable quality.
      The following five analytical themes were identified: functional restoration,
      psychological support, social engagement, spiritual experience, and short-comings
      and barriers. Conclusion: Creative arts-based therapies have demonstrated their
      strengths in addressing psychosocial needs for stroke survivors. Different art
      modalities are perceived to be useful in achieving different therapeutic goals.
      Therapies based on a single art modality or combined modalities have different
      specialties and characteristics. Further research is needed to demonstrate the
      differential benefits or special advantages of using single or multiple art
      modalities as well as having qualified therapists in creative arts-based
      therapies.

PMID- 30294288
TI  - Microexpressions Are Not the Best Way to Catch a Liar.

PMID- 30294289
TI  - Perpetuating Inequality: Junior Women Do Not See Queen Bee Behavior as Negative
      but Are Nonetheless Negatively Affected by It.
AB  - Previous research has revealed that women may attempt to avoid negative gender
      stereotypes in organizations through self-group distancing, or "queen bee",
      behaviors: emphasizing masculine qualities, distancing themselves from other
      women, and legitimizing organizational inequality. Factors that increase self
      group distancing have been identified (e.g., existing discrimination and low
      group identification), but it is unknown how self-group distancing by an ingroup
      leader is perceived by and affects subordinates of the negatively stereotyped
      group. In the current study, female participants received ambiguous negative
      feedback from a male versus female leader displaying queen bee-type versus
      neutral behavior. As expected, a male leader displaying queen bee-type behavior
      was seen as having less positive intent than a male leader displaying neutral
      behavior, which in turn increased how sexist he was perceived to be. A female
      leader displaying queen bee (vs. neutral) behavior was not seen as having less
      positive intent, which thus did not indirectly influence perceived sexism.
      Behavior of both male and female leaders did affect junior women: participants
      exposed to a leader displaying queen bee-type behavior reported more anger,
      sadness, and anxiety than participants exposed to a leader displaying neutral
      behavior. These data provide further evidence that simply adding more women or
      minorities in key senior positions is insufficient to change inequality if bias
      in the organization is not tackled. Specifically, exposure to gender inequality
      can steer female leaders to endorse-rather than change-stereotypes about women,
      and this behavior is particularly consequential because it (a) might not be
      recognized as bias and (b) exerts negative effects.

PMID- 30294290
TI  - Context-Sensitivity and Individual Differences in the Derivation of Scalar
      Implicature.
AB  - The derivation of scalar implicatures for the quantifier some has been widely
      studied to investigate the computation of pragmatically enriched meanings. For
      example, the sentence "I found some books" carries the semantic interpretation
      that at least one book was found, but its interpretation is often enriched to
      include the implicature that not all the books were found. The implicature is
      argued to be more likely to arise when it is relevant for addressing a question
      under discussion (QUD) in the context, e.g., when "I found some books" is uttered
      in response to "Did you find all the books?" as opposed to "Did you find any
      books?". However, most experimental studies have not examined the influence of
      context on some, instead testing some sentences in isolation. Moreover, no study
      to our knowledge has examined individual differences in the ability to utilize
      context in interpreting some, whereas individual variation in deriving
      implicatures for some sentences in isolation is widely attested, with alternative
      proposals attributing this variation to individual differences in cognitive
      resources (e.g., working memory) or personality-based pragmatic abilities (e.g.,
      as assessed by the Autism-Spectrum Quotient). The current study examined how
      context influences the interpretation of some in a story-sentence matching task,
      where participants rated some statements ("I cut some steaks") uttered by one
      character, in response to another character's question (QUD) that established the
      implicature as relevant ("Did you cut all the steaks?") or irrelevant ("Did you
      cut any steaks?"). We also examined to what extent individuals' sensitivity to
      QUD is modulated by individual differences via a battery of measures assessing
      cognitive resources, personality-based pragmatic abilities, and language
      abilities (which have been argued to modulate comprehension in other domains).
      Our results demonstrate that QUD affects the interpretation of some, and reveal
      that individual differences in sensitivity to QUD are modulated by both cognitive
      resources and personality-based pragmatic abilities. While previous studies have
      argued alternatively for cognitive resources or personality-based pragmatic
      abilities as important for deriving implicatures for some in isolation, we argue
      that arriving at a context-sensitive interpretation for some depends on both
      cognitive and personality-based properties of the individual.

PMID- 30294291
TI  - A Developmental Perspective on the Origins of Morality in Infancy and Early
      Childhood.
AB  - Key constituents of morality emerge during the first 4 years of life. Recent
      research with infants and toddlers holds a promise to explain the origins of
      human morality. This article takes a constructivist approach to the acquisition
      of morality, and makes three main proposals. First, research on moral development
      needs an explicit definition of morality. Definitions are crucial for scholarly
      communication and for settling empirical questions. Second, researchers would
      benefit from eschewing the dichotomy between innate and learned explanations of
      morality. Based on work on developmental biology, we propose that all
      developmental transitions involve both genetic and environmental factors. Third,
      attention is needed to developmental changes, alongside continuities, in the
      development of morality from infancy through childhood. Although infants and
      toddlers show behaviors that resemble the morally relevant behaviors of older
      children and adults, they do not judge acts as morally right or wrong until later
      in childhood. We illustrate these points by discussing the development of two
      phenomena central to morality: Orientations toward helping others and developing
      concepts of social equality. We assert that a constructivist approach will help
      to bridge research on infants and toddlers with research on moral developmental
      later in childhood and into adulthood.

PMID- 30294292
TI  - Spousal Support for Patients With Rheumatoid Arthritis: Getting the Wrong Kind Is
      a Pain.
AB  - Research indicates that perceived support availability is beneficial, with
      support available from the spouse particularly important for well-being. However,
      actual support mobilization has shown mixed associations with recipient well
      being. The primary goal of the present study was to go beyond examining the
      effects of global perceptions of support on recipient outcomes. Instead, we
      examined the effects of several specific types of support that have been found to
      be important in the clinical literature. In this study, we followed both members
      of couples in which one partner was diagnosed with rheumatoid arthritis. Patients
      provided reports on pain for both mornings and evenings across 1 week. Both
      partners also reported esteem, solicitous, and negative support mobilization
      received by the patient. We found that patient pain tended to increase across the
      day following increases in patient reports of negative support receipt and
      partner reports of solicitous support provision. We also found that patient pain
      tended to decrease across the day when partners reported increased levels of
      esteem support provision. Reverse causation analyses indicated higher levels of
      patient pain may lead partners to increase solicitous support mobilization to the
      patient. Findings underscore the importance of examining both partners' reports
      of support within a dyadic coping framework. They further suggest that not all
      forms of support are equally beneficial, calling for a finer grained assessment
      of specific support transactions.

PMID- 30294293
TI  - Role of the Cingulate Cortex in Dyskinesias-Reduced-Self-Awareness: An fMRI Study
      on Parkinson's Disease Patients.
AB  - Objectives: The detection of dyskinesias-reduced-self-awareness (DRSA), in
      Parkinson's disease (PD), was previously associated to executive and
      metacognitive deficits mainly due to dopaminergic overstimulation of
      mesocorticolimbic circuits. Response-inhibition dysfunction is often observed in
      PD. Apart from being engaged in response-inhibition tasks, the anterior cingulate
      cortex (ACC), is part of a functional system based on self-awareness and engaged
      across cognitive, affective and behavioural contexts. The purpose of the study
      was to examine the relationship between response-inhibition disabilities and DRSA
      using whole-brain event-related functional magnetic resonance imaging (fMRI),
      over the course of a specific executive task. Methods: Twenty-seven cognitively
      preserved idiopathic PD patients - presenting motor fluctuations and dyskinesias 
      were studied. They underwent a neurological and neuropsychological evaluation.
      The presence of DRSA was assessed using the Dyskinesias Subtracted-Index (DS-I).
      Cingulate functionality was evaluated with fMRI, while patients performed an ACC
      sensitive GO-NoGO task. Association between blood oxygenation level dependent
      response over the whole-brain during the response-inhibition task and DS-I scores
      was investigated by regression analysis. Results: The presence of DRSA was
      associated with reduced functional recruitment in the bilateral ACC, bilateral
      anterior insular cortex and right dorsolateral prefrontal cortex (pFWE <0.05).
      Moreover, DS-I scores significantly correlated with percent errors on the NoGO
      condition (r = 0.491, pFWE = 0.009). Discussion: These preliminary findings add
      evidence to the relevant role of executive dysfunctions in DRSA pathogenesis
      beyond the effects of chronic dopaminergic treatment, with a key leading role
      played by ACC as part of a functionally impaired response-inhibition network.
      Imaging biomarkers for DRSA are important to be studied, especially when the
      neuropsychological assessment seems to be normal.

PMID- 30294294
TI  - Single Dose of the Attention Training Technique Increases Resting Alpha and Beta
      Oscillations in Frontoparietal Brain Networks: A Randomized Controlled
      Comparison.
AB  - The Attention Training Technique (ATT) was developed with the aim of reducing
      self-focused attention and increasing executive control as part of metacognitive
      therapy. So far there is a paucity of data on the neurophysiological effects of
      ATT. In the present study we tested for specific effects to determine if
      attention control components of ATT elicit a specific signature that is different
      from passive listening. Thirty-six healthy volunteers were randomized to an
      active (follow instructions) or control (ignore instructions) condition. Resting
      state EEG was recorded for 3 min with eyes open and eyes closed before and after
      exposure to training, and the power of the theta, alpha, and beta-bands were
      analyzed in frontal, midline, and posterior electrodes. The active ATT condition
      enhanced alpha and beta-band activity during eyes-open, and frontal alpha during
      eyes-closed (p < 0.005). Frontoparietal changes in Alpha were generally
      accompanied by changes in Beta in the same brain regions of interest. However,
      these associations were largely significant in the active ATT rather than the
      control condition. No between-group differences were observed in the Theta-band.
      These results suggest a single dose of attention training increases alpha and
      beta-oscillations in frontoparietal networks. These networks are associated with
      top-down attentional or executive control.

PMID- 30294295
TI  - Different Mechanisms of Two Subtypes of Perforating Artery Infarct in the Middle
      Cerebral Artery Territory: A High-Resolution Magnetic Resonance Imaging Study.
AB  - Purpose: Perforating Artery Infarcts (PAIs) can be divided into two subtypes
      based on their etiologies: branch Atheromatous Disease (BAD) and Lacunar Infarct
      (LI). Recent studies have shown that while both subtypes can be caused by large
      artery lesions, the different mechanisms that underlie their development are not
      clear. This study was designed to use High-Resolution Magnetic Resonance Imaging
      (HRMRI) to explore the differences that contribute to the occurrence of these two
      subtypes in large artery lesions in the anterior circulation. Methods: Fifty
      patients with an acute PAI in the anterior circulation were enrolled (32 BAD and
      18 LI patients). The ipsilateral middle cerebral artery (MCA) was scanned with
      HRMRI to analyze the atherosclerosis plaques. Artery remodeling and plaque
      characteristics of MCA lesions were compared between the two subtypes. Results:
      The rate of MCA lesions was significantly higher in BAD and substantially lower
      in LI (P = 0.033). LAs for the lumen areas in Bad, they were smaller than LI (P <
      0.001), Additionally, the plaque area (P = 0.001) and plaque burden (P < 0.001)
      were superior in the BAD group. Most BAD patients displayed non-positive
      remodeling, while the great majority of LI patients showed positive remodeling (P
      < 0.001). Conclusion: In the anterior circulation, a considerable amount of BAD
      and LI share similarities with atherosclerotic plaques in large arteries. BAD
      patients mainly showed relatively large and stable atherosclerotic plaques in
      large arteries, while LI patients mainly exhibited relatively small and unstable
      atherosclerotic plaques. Clinical Trial Registration: This clinical trial is a
      retrospective study and therefore does not require registration.

PMID- 30294296
TI  - The Importance of Inter-Species Variation in Traumatic Brain Injury-Induced
      Alterations of Microglial-Axonal Interactions.
AB  - Interactions between microglia and neuronal components are important for normal
      CNS function. They are also associated with neuroinflammation and many
      pathological processes and several studies have explored these interactions in
      terms of phagocytic engulfment. Much progress has also been made in understanding
      the consequences of chronic neuroinflammatory changes following trauma. However,
      little is known about acute alterations to these physical non-phagocytic
      microglial-neuronal interactions following traumatic brain injury (TBI), and
      particularly to what degree these post-injury interactions may be influenced by
      the animal species utilized in pre-clinical models of TBI. To investigate these
      problems, we evaluated the physical interactions between microglia and injured
      axons acutely (6 h and 1 day) following central fluid percussion injury (cFPI) in
      both rats and micro pigs. The physical interactions between Iba-1+ microglia and
      either normal MBP+ myelinated fibers or APP+ injured axonal swellings in the
      thalamus were assessed following injury or sham via quantitative image analysis
      of 3D confocal micrographs. The results indicated that the physical interactions
      between microglia and injured axonal swellings decreased by nearly half in rats 6
      h following cFPI but was consistent with sham control at 1 day post-cFPI. This
      reduction was also observed in non-injured intact fibers at both timepoints
      following TBI in the rat. Microglial process interactions with injured axons in
      the micro pig, however, increased nearly 2-fold compared to interactions with
      intact axonal segments 1 day post-cFPI. This study shows that the species
      utilized for in vivo pre-clinical studies influences the manner in which
      microglial-axonal interactions change following TBI. These species differences
      can be leveraged to further our understanding of the mechanisms involved in
      microglial process convergence and how these neuro-immune interactions alter the
      progression of axonal injury following TBI.

PMID- 30294297
TI  - Effects of Dehydration on Brain Perfusion and Infarct Core After Acute Middle
      Cerebral Artery Occlusion in Rats: Evidence From High-Field Magnetic Resonance
      Imaging.
AB  - Background: Dehydration is common among ischemic stroke patients and is
      associated with early neurological deterioration and poor outcome. This study
      aimed to test the hypothesis that dehydration status is associated with decreased
      cerebral perfusion and aggravation of ischemic brain injury. Methods: Diffusion
      weighted imaging and arterial spin labeling perfusion MR imaging were performed
      on rats with middle cerebral artery occlusion (MCAO) by using a 9.4T MR imaging
      scanner to measure the volume of infarction and relative cerebral blood flow
      (rCBF) after infarction. Twenty-five rats were assigned to either a dehydration
      group or normal hydration group, and dehydration status was achieved by water
      deprivation for 48 h prior to MCAO. Results: The volume of the infarction was
      significantly larger for the dehydration group at the 4th h after MCAO (p =
      0.040). The progression in the infarct volume between the 1st and 4th h was also
      larger in the dehydration group (p = 0.021). The average rCBF values of the
      contralateral normal hemispheres at the 1st and the 4th h were significantly
      lower in the dehydration group (p = 0.027 and 0.040, respectively). Conclusions:
      Our findings suggested that dehydration status is associated with the progression
      of infarct volume and decreases in cerebral blood flow during the acute stage of
      ischemic stroke. This preliminary study provided an imaging clue that more
      intensive hydration therapies and reperfusion strategies are necessary for the
      management of acute ischemic stroke patients with dehydration status.

PMID- 30294298
TI  - Editorial: Beyond Borders: Myotonic Dystrophies-A European Perception.

PMID- 30294299
TI  - Caffeine Consumption and Mortality in Diabetes: An Analysis of NHANES 1999-2010.
AB  - Aim: An inverse relationship between coffee consumption and mortality has been
      reported in the general population. However, the effect of coffee consumption in
      diabetes remains unclear. We aimed to evaluate the association of caffeine
      consumption and caffeine source with mortality among patients with diabetes.
      Methods: We examined the association of caffeine consumption with mortality among
      1974 women and 1974 men with diabetes, using the National Health and Nutrition
      Examination Survey (NHANES) 1999-2010. Caffeine consumption was assessed at
      baseline using 24 h dietary recalls. Cox proportional hazard models were fitted
      to estimate hazard ratios (HR) for all-cause, cardiovascular, and cancer-related
      mortality according to caffeine consumption and its source, adjusting for
      potential confounders. Results: A dose-dependent inverse association between
      caffeine and all-cause mortality was observed in women with diabetes. Adjusted HR
      for death among women who consumed caffeine, as compared with non-consumers,
      were: 0.57 (95% CI, 0.40-0.82) for <100 mg of caffeine/day, 0.50 (95% CI, 0.32
      0.78) for 100 to <200 mg of caffeine/day, and 0.39 (95% CI, 0.23-0.64) for >=200
      mg of caffeine/day (p = 0.005 for trend). This association was not observed in
      men. There was a significant interaction between sex and caffeine consumption (p
      = 0.015). No significant association between total caffeine consumption and
      cardiovascular or cancer mortality was observed. Women who consumed more caffeine
      from coffee had reduced risk of all-cause mortality (p = 0.004 for trend).
      Conclusion: Our study showed a dose-dependent protective effect of caffeine
      consumption on mortality among women with diabetes.

PMID- 30294301
TI  - Vitamin D Toxicity-A Clinical Perspective.
AB  - Confusion, apathy, recurrent vomiting, abdominal pain, polyuria, polydipsia, and
      dehydration are the most often noted clinical symptoms of vitamin D toxicity
      (VDT; also called vitamin D intoxication or hypervitaminosis D). VDT and its
      clinical manifestation, severe hypercalcemia, are related to excessive long-term
      intake of vitamin D, malfunctions of the vitamin D metabolic pathway, or the
      existence of coincident disease that produces the active vitamin D metabolite
      locally. Although VDT is rare, the health effects can be serious if it is not
      promptly identified. Many forms of exogenous (iatrogenic) and endogenous VDT
      exist. Exogenous VDT is usually caused by the inadvertent or improper intake of
      extremely high doses of pharmacological preparations of vitamin D and is
      associated with hypercalcemia. Serum 25-hydroxyvitamin D [25(OH)D] concentrations
      higher than 150 ng/ml (375 nmol/l) are the hallmark of VDT due to vitamin D
      overdosing. Endogenous VDT may develop from excessive production of an active
      vitamin D metabolite - 1,25(OH)2D in granulomatous disorders and in some
      lymphomas or from the reduced degradation of that metabolite in idiopathic
      infantile hypercalcemia. Endogenous VDT may also develop from an excessive
      production of 25(OH)D and 1,25(OH)2D in congenital disorders, such as Williams
      Beuren syndrome. Laboratory testing during routine clinical examinations may
      reveal asymptomatic hypercalcemia caused by the intake of vitamin D even in doses
      recommended for the general population and considered safe. That phenomenon,
      called hypersensitivity to vitamin D, reflects dysregulated vitamin D metabolism.
      Researchers have proposed many processes to explain VDT. Those processes include
      elevated activity of 1alpha-hydroxylase or inhibited activity of 24-hydroxylase,
      both leading to increased concentration of 1,25(OH)D; increased number of vitamin
      D receptors; and saturation of the capacity of vitamin D binding protein.
      Increased public awareness of vitamin D-related health benefits might increase
      the risk of VDT due to self-administration of vitamin D in doses higher then
      recommended for age and body weight or even higher than the established upper
      limit intake values. Consequently, the incidence of hypercalcemia due to
      hypervitaminosis D might increase.

PMID- 30294300
TI  - Developmental Exposure to 2,2',4,4'-Tetrabromodiphenyl Ether Permanently Alters
      Blood-Liver Balance of Lipids in Male Mice.
AB  - Polybrominated diphenyl ethers (PBDEs) were used as flame-retardant additives
      starting 1965 and were recently withdrawn from commerce in North America and
      Europe. Approximately 1/5 of the total U.S. population were born when
      environmental concentrations of PBDE plateaued at their maximum. Accumulating
      evidence suggests that developmental exposures to PBDE may result in long-lasting
      programming of liver metabolism. In this study, CD-1 mice were exposed prenatally
      or neonatally to 1 mg/kg body weight of 2,2',4,4'-tetrabromodiphenyl ether (BDE
      47), and changes in liver histology, transcriptome, and liver-blood balance of
      triglycerides were analyzed in 10 months old male offspring. In both exposure
      groups, long-term reprogramming of lipid metabolism was observed, including
      increased liver triglycerides and decreased blood triglycerides, and altered
      expression of metabolic genes in the liver. Significant upregulation of lipid
      influx transporter Cd36 2.3- and 5.7-fold in pre- and neonatal exposure groups,
      respectively was identified as a potential mechanism of blood/liver imbalance of
      triglycerides. Analysis of our and previously published all-genome gene
      expression data identified changes in expression of ribosomal protein genes as a
      transcriptomic signature of PBDE exposure. Further comparison of our new data and
      published data demonstrate that low doses (0.2 mg/kg body weight) of PBDE induce
      long-lasting up-regulation of ribosomal genes, suppression of Cd36 in liver and
      increase circulating triglycerides in blood, while moderated doses (>=1 mg/kg
      body weight) produce opposite long-lasting effects. To conclude, this study shows
      that an environmentally relevant developmental exposures to BDE-47 permanently
      alter lipid uptake and accumulation in the liver, with low and moderate doses
      having opposite effect on liver transcriptomics and triglyceride balance. Similar
      effects of pre- and neonatal exposures point at hepatocyte maturation as a
      sensitive window of the liver metabolism programming. These results suggest that
      PBDE exposure may be an important factor increasing risks of cardio-vascular
      disease and non-alcoholic fatty liver disease via modulation of liver/blood
      balance of lipids. The translational relevance of these findings for human remain
      to be studied.

PMID- 30294302
TI  - Associations Between C-Reactive Protein, Insulin Sensitivity, and Resting
      Metabolic Rate in Adults: A Mediator Analysis.
AB  - Objective: Long-term positive energy balance promotes the development of obesity,
      a main risk factor for type 2 diabetes mellitus (T2DM). While an association
      between increased resting metabolic rate (RMR) and insulin sensitivity (IS) was
      shown previously, the underlying mechanisms remain unclear. Aim of the mediator
      analysis was to investigate the role of inflammation within the association
      between RMR and IS. Methods: Anthropometric, clinical, and lifestyle data were
      collected according to standard operating procedures. RMR was measured using
      indirect calorimetry. Homeostasis model assessment for insulin resistance (HOMA
      IR) was used as an IS parameter and C-reactive protein (CRP) was measured to
      represent the inflammatory status. Statistical analyses were performed using
      SPSS. Results: The analysis included 782 adults (517 females) with a mean age of
      32.4 +/- 12.0 years and a mean body mass index (BMI) of 24.6 +/- 5.2 kg/m2.
      Regression analysis indicated a significant evidence for associations between RMR
      and HOMA-IR (beta = 39.3 +/- 7.3 kcal/d; p <= 0.001) and CRP and HOMA-IR (beta =
      0.5 +/- 0.1; p <= 0.001) after adjustment for fat-free mass, sex, age, and study
      site. Results of the mediator analysis did not support the hypothesis that CRP is
      a mediator for the association between RMR and HOMA-IR. These results did not
      change after participant stratification according to sex or BMI. Conclusion: A
      significant evidence for an association between RMR and IS was shown in a large
      cohort. However, the inflammatory status, determined via CRP levels, was not a
      mediator within this association.

PMID- 30294303
TI  - An Association of PTPN11 and SHOX Mutations in a Male Presenting With Syndromic
      Growth Failure.
AB  - In children with genetic syndromes, short stature is frequently a characteristic
      feature that, when associated with other specific manifestations, significantly
      aids in clinical diagnosis. In this report, an atypical case of Noonan syndrome
      (NS) in a 5.5-year-old child with mesomelic short stature is described. Genetic
      tests revealed two different mutations in this child. As expected in an NS case,
      a mutation in PTPN11 gene related to the RAS/MAPK signal transduction pathway was
      identified. Moreover, a mutation in the SHOX gene that was able to cause
      disproportionate short stature was detected. A clinical picture of NS with
      mesomelic short stature makes the diagnosis even more difficult as
      haploinsufficiency and complete loss of function of SHOX gene are associated with
      the typical differentiation and proliferation of chondrocytes, leading to
      mesomelic appearance. This case exemplifies the difficulties that can be
      encountered in achieving proper diagnoses for children with syndromic diseases
      and highlights the role of genetic tests in identifying final diagnoses in these
      patients.

PMID- 30294305
TI  - Desiccation- and Saline-Tolerant Bacteria and Archaea in Kalahari Pan Sediments.
AB  - More than 41% of the Earth's land area is covered by permanent or seasonally arid
      dryland ecosystems. Global development and human activity have led to an increase
      in aridity, resulting in ecosystem degradation and desertification around the
      world. The objective of the present work was to investigate and compare the
      microbial community structure and geochemical characteristics of two
      geographically distinct saline pan sediments in the Kalahari Desert of southern
      Africa. Our data suggest that these microbial communities have been shaped by
      geochemical drivers, including water content, salinity, and the supply of organic
      matter. Using Illumina 16S rRNA gene sequencing, this study provides new insights
      into the diversity of bacteria and archaea in semi-arid, saline, and low-carbon
      environments. Many of the observed taxa are halophilic and adapted to water
      limiting conditions. The analysis reveals a high relative abundance of halophilic
      archaea (primarily Halobacteria), and the bacterial diversity is marked by an
      abundance of Gemmatimonadetes and spore-forming Firmicutes. In the deeper, anoxic
      layers, candidate division MSBL1, and acetogenic bacteria (Acetothermia) are
      abundant. Together, the taxonomic information and geochemical data suggest that
      acetogenesis could be a prevalent form of metabolism in the deep layers of a
      saline pan.

PMID- 30294304
TI  - Grow With the Challenge - Microbial Effects on Epithelial Proliferation,
      Carcinogenesis, and Cancer Therapy.
AB  - The eukaryotic host is in close contact to myriads of resident and transient
      microbes, which influence the crucial physiological pathways. Emerging evidence
      points to their role of host-microbe interactions for controlling tissue
      homeostasis, cell fate decisions, and regenerative capacity in epithelial barrier
      organs including the skin, lung, and gut. In humans and mice, it has been shown
      that the malignant tumors of these organs harbor an altered microbiota.
      Mechanistic studies have shown that the altered metabolic properties and secreted
      factors contribute to epithelial carcinogenesis and tumor progression. Exciting
      recent work points toward a crucial influence of the associated microbial
      communities on the response to chemotherapy and immune-check point inhibitors
      during cancer treatment, which suggests that the modulation of the microbiota
      might be a powerful tool for personalized oncology. In this article, we provide
      an overview of how the bacterial signals and signatures may influence epithelial
      homeostasis across taxa from cnidarians to vertebrates and delineate mechanisms,
      which might be potential targets for therapy of human diseases by either
      harnessing barrier integrity (infection and inflammation) or restoring
      uncontrolled proliferation (cancer).

PMID- 30294307
TI  - Dispersal Modifies the Diversity and Composition of Active Bacterial Communities
      in Response to a Salinity Disturbance.
AB  - Dispersal can influence the response of bacterial communities to environmental
      changes and disturbances. However, the extent to which dispersal contributes to
      the community response in dependence of the character and strength of the
      disturbance remains unclear. Here, we conducted a transplant experiment using
      dialysis bags in which bacterioplankton originating from brackish and marine
      regions of the Saint Lawrence Estuary were reciprocally incubated in the two
      environments for 5 days. Dispersal treatments were set-up by subjecting half of
      the microcosms in each environment to an exchange of cells between the marine and
      brackish assemblages at a daily exchange rate of 6% (v/v), and the other half of
      microcosms were kept as the non-dispersal treatments. Bacterial 16S rRNA
      sequencing was then used to examine the diversity and composition of the active
      communities. Alpha diversity of the marine communities that were exposed to the
      brackish environment was elevated greatly by dispersal, but declined in the
      absence of dispersal. This indicates that dispersal compensated the loss of
      diversity in the marine communities after a disturbance by introducing bacterial
      taxa that were able to thrive and coexist with the remaining community members
      under brackish conditions. On the contrary, alpha diversity of the brackish
      communities was not affected by dispersal in either environment. Furthermore,
      dispersal led to an increase in similarity between marine and brackish
      communities in both of the environments, with a greater similarity when the
      communities were incubated in the brackish environment. These results suggest
      that the higher initial diversity in the brackish than in the marine starting
      community made the resident community less susceptible to dispersing bacteria.
      Altogether, this study shows that dispersal modifies the diversity and
      composition of the active communities in response to a salinity disturbance, and
      enables the local adjustment of specific bacteria under brackish environmental
      conditions.

PMID- 30294306
TI  - Determinants of Deadwood-Inhabiting Fungal Communities in Temperate Forests:
      Molecular Evidence From a Large Scale Deadwood Decomposition Experiment.
AB  - Despite the important role of wood-inhabiting fungi (WIF) in deadwood
      decomposition, our knowledge of the factors shaping the dynamics of their species
      richness and community composition is scarce. This is due to limitations
      regarding the resolution of classical methods used for characterizing WIF
      communities and to a lack of well-replicated long-term experiments with
      sufficient numbers of tree species. Here, we used a large scale experiment with
      logs of 11 tree species at an early stage of decomposition, distributed across
      three regions of Germany, to identify the factors shaping WIF community
      composition and Operational Taxonomic Unit (OTU) richness using next generation
      sequencing. We found that tree species identity was the most significant factor,
      corresponding to (P < 0.001) and explaining 10% (representing 48% of the
      explainable variance) of the overall WIF community composition. The next
      important group of variables were wood-physicochemical properties, of which wood
      pH was the only factor that consistently corresponded to WIF community
      composition. For overall WIF richness patterns, we found that approximately 20%
      of the total variance was explained by wood N content, location, tree species
      identity and wood density. It is noteworthy that the importance of determinants
      of WIF community composition and richness appeared to depend greatly on tree
      species group (broadleaved vs. coniferous) and it differed between the fungal
      phyla Ascomycota and Basidiomycota.

PMID- 30294308
TI  - Diversity of Bradyrhizobia in Subsahara Africa: A Rich Resource.
AB  - Making use of biological nitrogen fixation (BNF) with pulses and green manure
      legumes can help to alleviate nitrogen deficiencies and increase soil fertility,
      problems faced particularly in smallholder agriculture in Subsahara Africa (SSA).
      The isolation of indigenous rhizobia provides a basis for the formulation of
      rhizobial inoculants. Moreover, their identification and characterization
      contribute to the general understanding of species distribution and ecology. Here
      we discuss global species discovery of Bradyrhizobium spp. Although recently the
      number of validly published Bradyrhizobium species is rapidly increasing, their
      diversity in SSA is not well-represented. We summarize the recent knowledge on
      species diversity in the Bradyrhizobium yuanmingense lineage to which most SSA
      isolates belong, and their biogeographic distribution and adaptations. Most
      indigenous rhizobia appear to differ from species found on other continents. We
      stress that an as yet hidden diversity may be a rich resource for inoculant
      development in future. As some species are exceptionally temperature tolerant,
      they may be potential biofertilizer candidates for global warming scenarios.

PMID- 30294309
TI  - Efficiency of Biosynthesized Silver and Zinc Nanoparticles Against Multi-Drug
      Resistant Pathogens.
AB  - Biosynthesis of metallic nanoparticles has acquired particular attention due to
      its economic feasibility, low toxicity, and simplicity of the process. In this
      study, extracellular synthesis of silver and zinc nanoparticle was carried out by
      Pseudomonas hibiscicola isolated from the effluent of an electroplating industry
      in Mumbai. Characterization studies revealed synthesis of 40 and 60 nm
      nanoparticles of silver (AgNP) and zinc (ZnNP), respectively, with distinct
      morphology as observed in TEM and its crystalline nature confirmed by XRD. DLS,
      zeta potential, NTA, and FTIR studies further characterized nanoparticles giving
      data about its size, stability, and functional groups. Considering the toxicity
      of nanoparticles the evaluation of antimicrobial activity was studied in the
      range of non-toxic concentration for normal cell lines. Silver nanoparticles were
      found to be the most effective antimicrobial against all tested strains and drug
      resistant clinical isolates of MRSA, VRE, ESBL, MDR, Pseudomonas aeruginosa with
      MIC in the range of 1.25-5 mg/ml. Zinc nanoparticles were found to be
      specifically active against Gram-positive bacteria like Staphylococcus aureus
      including its drug-resistant variant MRSA. Both AgNP and ZnNP were found to be
      effective against Mycobacterium tuberculosis and its MDR strain with MIC of 1.25
      mg/ml. The synergistic action of nanoparticles assessed in combination with a
      common antibiotic gentamicin (590 MUg/mg) used for the treatment of various
      bacterial infections by Checker board assay. Silver nanoparticles profoundly
      exhibited synergistic antimicrobial activity against drug-resistant strains of
      MRSA, ESBL, VRE, and MDR P. aeruginosa while ZnNP were found to give synergism
      with gentamicin only against MRSA. The MRSA, ESBL, and P. aeruginosa strains
      exhibited MIC of 2.5 mg/ml except VRE which was 10 mg/ml for both AgNPs and
      ZnNPs. These results prove the great antimicrobial potential of AgNP and ZnNP
      against drug-resistant strains of community and hospital-acquired infections and
      opens a new arena of antimicrobials for treatment, supplementary prophylaxis, and
      prevention therapy.

PMID- 30294310
TI  - Genomic Characterization and Probiotic Potency of Bacillus sp. DU-106, a Highly
      Effective Producer of L-Lactic Acid Isolated From Fermented Yogurt.
AB  - Bacillus sp. DU-106, a newly isolated member of Bacillus cereus group, exhibits
      the predominant ability to produce L-lactic acid. The probiotic potency of test
      strain revealed its survivability at acidic pH, bile salts and viability in
      simulated gastric juice in vitro. The acute oral toxicity test indicated its no
      toxicity to laboratory mice in vivo. We further determined the complete genome of
      strain DU-106 to understand genetic basis as a potential probiotic. It has a
      circular chromosome and three plasmids for a total genome 5,758,208 bp in size
      with a G + C content of 35.10%. Genes associated with lactate synthesis were
      found in the DU-106 genome. We also annotated various stress-related, bile salt
      resistance, and adhesion-related domains in this strain, which likely provide
      support in exerting probiotic action by enabling adhesion to host epithelial
      cells and survival under gastrointestinal tract. Moreover, strain DU-106 genome
      lacks the virulence genes encodes cereulide synthetase, enterotoxin FM, and
      cytotoxin K. These phenotypic and genomic probiotic potencies facilitate its
      potential candidate as probiotic starter in food industry.

PMID- 30294312
TI  - Characterization of Cell Envelope Multiple Mutants of Brucella ovis and
      Assessment in Mice of Their Vaccine Potential.
AB  - Brucella ovis is a non-zoonotic Brucella species lacking specific vaccine. It
      presents a narrow host range, a unique biology relative to other Brucella
      species, and important distinct surface properties. To increase our knowledge on
      its peculiar surface and virulence features, and seeking to develop a specific
      vaccine, multiple mutants for nine relevant cell-envelope-related genes were
      investigated. Mutants lacking Omp10 plus Omp19 could not be obtained, suggesting
      that at least one of these lipoproteins is required for viability. A similar
      result was obtained for the double deletion of omp31 and omp25 that encode two
      major surface proteins. Conversely, the absence of major Omp25c (proved essential
      for internalization in HeLa cells) together with Omp25 or Omp31 was tolerated by
      the bacterium. Although showing important in vitro and in vivo defects, the
      Deltaomp10Deltaomp31Deltaomp25c mutant was obtained, demonstrating that B. ovis
      PA survives to the simultaneous absence of Omp10 and four out seven proteins of
      the Omp25/Omp31 family (i.e., Omp31, Omp25c, Omp25b, and Omp31b, the two latter
      naturally absent in B. ovis). Three multiple mutants were selected for a detailed
      analysis of virulence in the mouse model. The Deltaomp31Deltacgs and
      Deltaomp10Deltaomp31Deltaomp25c mutants were highly attenuated when inoculated at
      106 colony forming units/mouse but they established a persistent infection when
      the infection dose was increased 100-fold. The Deltaomp10DeltaugpBDeltaomp31
      mutant showed a similar behavior until week 3 post-infection but was then totally
      cleared from spleen. Accordingly, it was retained as vaccine candidate for mice
      protection assays. When compared to classical B. melitensis Rev1 heterologous
      vaccine, the triple mutant induced limited splenomegaly, a significantly higher
      antibody response against whole B. ovis PA cells, an equivalent memory cellular
      response and, according to spleen colonization measurements, better protection
      against a challenge with virulent B. ovis PA. Therefore, it would be a good
      candidate to be evaluated in the natural host as a specific vaccine against B.
      ovis that would avoid the drawbacks of B. melitensis Rev1. In addition, the lack
      in this attenuated strain of Omp31, recognized as a highly immunogenic protein
      during B. ovis infection, would favor the differentiation between infected and
      vaccinated animals using Omp31 as diagnostic target.

PMID- 30294311
TI  - Characterization and Salt Response in Recurrent Halotolerant Exiguobacterium sp.
      SH31 Isolated From Sediments of Salar de Huasco, Chilean Altiplano.
AB  - Poly-extremophiles microorganisms have the capacity to inhabit hostile
      environments and can survive several adverse conditions that include as
      variations in temperature, pH, and salinity, high levels UV light and atmospheric
      pressure, and even the presence of toxic compounds and the formation of reactive
      oxygen species (ROS). A halotolerant Exiguobacterium strain was isolated from
      Salar de Huasco (Chilean Altiplano), a well-known shallow lake area with variable
      salinity levels, little human intervention, and extreme environmental conditions,
      which makes it ideal for the study of resistant mechanisms and the evolution of
      adaptations. This bacterial genus has not been extensively studied, although its
      cosmopolitan location indicates that it has high levels of plasticity and
      adaptive capacity. However, to date, there are no studies regarding the tolerance
      and resistance to salinity and osmotic pressure. We set out to characterize the
      Exiguobacterium sp. SH31 strain and describe its phenotypical and genotypical
      response to osmotic stress. In this context, as a first step to characterize the
      response to the SH31 strain to salinity and to establish the bases for a
      molecular study, we proposed to compare its response under three salt conditions
      (0, 25, and 50 g/l NaCl). Using different physiology, genomic, and transcriptomic
      approaches, we determined that the bacterium is able to grow properly in a NaCl
      concentration of up to 50 g/l; however, the best growth rate was observed at 25
      g/l. Although the presence of flagella is not affected by salinity, motility was
      diminished at 25 g/l NaCl and abolished at 50 g/l. Biofilm formation was induced
      proportionally with increases in salinity, which was expected. These phenotypic
      results correlated with the expression of related genes: fliG and fliS Motility);
      opuBA and putP (transport); glnA, proC, gltA, and gbsA (compatible solutes);
      ywqC, bdlA, luxS y pgaC (biofilm and stress response); and therefore, we conclude
      that this strain effectively modifies gene expression and physiology in a
      differential manner when faced with different concentrations of NaCl and these
      modifications aid survival.

PMID- 30294314
TI  - Surveillance for Azole-Resistant Aspergillus fumigatus in a Centralized
      Diagnostic Mycology Service, London, United Kingdom, 1998-2017.
AB  - Background/Objectives: Aspergillus fumigatus is the leading cause of invasive
      aspergillosis. Treatment is hindered by the emergence of resistance to triazole
      antimycotic agents. Here, we present the prevalence of triazole resistance among
      clinical isolates at a major centralized medical mycology laboratory in London,
      United Kingdom, in the period 1998-2017. Methods: A large number (n = 1469) of
      clinical A. fumigatus isolates from unselected clinical specimens were identified
      and their susceptibility against three triazoles, amphotericin B and three
      echinocandin agents was carried out. All isolates were identified phenotypically
      and antifungal susceptibility testing was carried out by using a standard broth
      microdilution method. Results: Retrospective surveillance (1998-2011) shows
      5/1151 (0.43%) isolates were resistant to at least one of the clinically used
      triazole antifungal agents. Prospective surveillance (2015-2017) shows 7/356
      (2.2%) isolates were resistant to at least one triazole antifungals demonstrating
      an increase in incidence of triazole-resistant A. fumigatus in our laboratory.
      Among five isolates collected from 2015 to 2017 and available for molecular
      testing, three harbored TR34/L98H alteration in the cyp51A gene that are
      associated with the acquisition of resistance in the non-patient environment.
      Conclusion: These data show that historically low prevalence of azole resistance
      may be increasing, warranting further surveillance of susceptible patients.

PMID- 30294313
TI  - Optimization and Lead Selection of Benzothiazole Amide Analogs Toward a Novel
      Antimycobacterial Agent.
AB  - Mycobacteria remain an important problem worldwide, especially drug resistant
      human pathogens. Novel therapeutics are urgently needed to tackle both drug
      resistant tuberculosis (TB) and difficult-to-treat infections with nontuberculous
      mycobacteria (NTM). Benzothiazole adamantyl amide had previously emerged as a
      high throughput screening hit against M. tuberculosis (Mtb) and was subsequently
      found to be active against NTM as well. For lead optimization, we applied an
      iterative process of design, synthesis and screening of several 100 analogs to
      improve antibacterial potency as well as physicochemical and pharmacological
      properties to ultimately achieve efficacy. Replacement of the adamantyl group
      with cyclohexyl derivatives, including bicyclic moieties, resulted in advanced
      lead compounds that showed excellent potency and a mycobacteria-specific spectrum
      of activity. MIC values ranged from 0.03 to 0.12 MUg/mL against M. abscessus
      (Mabs) and other rapid- growing NTM, 1-2 MUg/mL against M. avium complex (MAC),
      and 0.12-0.5 MUg/mL against Mtb. No pre-existing resistance was found in a
      collection of n = 54 clinical isolates of rapid-growing NTM. Unlike many
      antibacterial agents commonly used to treat mycobacterial infections,
      benzothiazole amides demonstrated bactericidal effects against both Mtb and Mabs.
      Metabolic labeling provided evidence that the compounds affect the transfer of
      mycolic acids to their cell envelope acceptors in mycobacteria. Mapping of
      resistance mutations pointed to the trehalose monomycolate transporter (MmpL3) as
      the most likely target. In vivo efficacy and tolerability of a benzothiazole
      amide was demonstrated in a mouse model of chronic NTM lung infection with Mabs.
      Once daily dosing over 4 weeks by intrapulmonary microspray administration as 5%
      corn oil/saline emulsion achieved statistically significant CFU reductions
      compared to vehicle control and non-inferiority compared to azithromycin. The
      benzothiazole amides hold promise for development of a novel therapeutic agent
      with broad antimycobacterial activity, though further work is needed to develop
      drug formulations for direct intrapulmonary delivery via aerosol.

PMID- 30294315
TI  - Engineering Heterologous Production of Salicylate Glucoside and Glycosylated
      Variants.
AB  - Salicylate 2-O-beta-D-glucoside (SAG) is a plant-derived natural product with
      potential utility as both an anti-inflammatory and as a plant protectant
      compound. Heterologous biosynthesis of SAG has been established in Escherichia
      coli through metabolic engineering of the shikimate pathways and introduction of
      a heterologous biosynthetic step to allow a more directed route to the salicylate
      precursor. The final SAG compound resulted from the separate introduction of an
      Arabidopsis thaliana glucosyltransferase enzyme. In this study, a range of
      heterologous engineering parameters were varied (including biosynthetic pathway
      construction, expression plasmid, and E. coli strain) for the improvement of SAG
      specific production in conjunction with a system demonstrating improved plasmid
      stability. In addition, the glucoside moiety of SAG was systematically varied
      through the introduction of the heterologous oliose and olivose deoxysugar
      pathways. Production of analogs was observed for each newly constructed pathway,
      demonstrating biosynthetic diversification potential; however, production titers
      were reduced relative to the original SAG compound.

PMID- 30294316
TI  - Acyl Carrier Protein 3 Is Involved in Oxidative Stress Response in Pseudomonas
      aeruginosa.
AB  - The human opportunistic pathogen Pseudomonas aeruginosa expresses three acyl
      carrier proteins (ACPs): AcpP, Acp1, and Acp3. The function of AcpP in membrane
      fatty acid synthesis (FAS) was confirmed recently, but the physiological roles of
      Acp1 and Acp3 remain unclear. To address this, we investigated the physiological
      role of Acp3 in P. aeruginosa. We found that expression of Acp3 dramatically
      increases in the log phase of cell growth and that its transcription is under the
      control of the QS regulators LasR and RhlR. Deletion of acp3 from P. aeruginosa
      strain PAO1 results in thicker biofilm formation, increased resistance of the
      strain to hydrogen peroxide, and higher persistence in a mouse infection model.
      Tandem affinity purification (TAP) experiments revealed several novel protein
      binding partners of Acp3, including KatA, the major catalase in P. aeruginosa.
      Acp3 was found to repress the catalase activity of KatA and, consistent with
      inhibition by Acp3, less reactive oxygen species are present in the acp3 deletion
      strain. Overall, our study reveals that Acp3 has a distinct function from that of
      the canonical AcpP and may be involved in the oxidative stress response.

PMID- 30294317
TI  - A Nematode of the Mid-Atlantic Ridge Hydrothermal Vents Harbors a Possible
      Symbiotic Relationship.
AB  - Deep-sea hydrothermal vent meiofauna have been the focus of recent research and
      the discovery of an abundant well-adapted free-living marine nematode on the Mid
      Atlantic Ridge offers new perspectives on adaptations to the vent environment.
      Indeed, knowledge concerning biological interactions of microbes and meiofauna in
      marine extreme environments is scarce, especially for nematodes. In this study,
      we used microscopic observations [fluorescence in situ hybridization (FISH) and
      scanning electron microscopy (SEM)] and metabarcoding of 16S rRNA to characterize
      the bacterial community of the nematode species Oncholaimus dyvae, an overlooked
      but ecologically important vent organism. Detection of bacteria in the buccal
      cavity and on the cuticle (SEM) and epibionts in its intestine (FISH) suggests
      that O. dyvae harbors its own bacterial community. Molecular results and
      phylogenetic analysis show that bacteria associated with this species are related
      to symbiotic lineages typical of hydrothermal vent fauna, such as sulfur
      oxidizing bacteria related to Epsilonproteobacteria and Gammaproteobacteria. This
      multi-approach study suggests a potential symbiotic role of bacteria with its
      nematode host and opens new research perspectives on vent meiofauna.

PMID- 30294319
TI  - Gene Expression Order Attributed to Genome Reduction and the Steady Cellular
      State in Escherichia coli.
AB  - Transcriptomes not only reflect the growth status but also link to the genome in
      bacteria. To investigate if and how genome or cellular state changes contribute
      to the gene expression order, the growth profile-associated transcriptomes of an
      assortment of genetically differentiated Escherichia coli either exponentially
      growing under varied conditions or in response to environmental disturbance were
      analyzed. A total of 168 microarray data sets representing 56 transcriptome
      variations, were categorized by genome size (full length or reduced) and cellular
      state (steady or unsteady). At the genome-wide level, the power-law distribution
      of gene expression was found to be significantly disturbed by the genome size but
      not the cellular state. At the regulatory network level, more networks with
      improved coordination of growth rates were observed in genome reduction than at
      the steady state. At the single-gene level, both genome reduction and steady
      state increased the correlation of gene expression to growth rate, but the
      enriched gene categories with improved correlations were different. These
      findings not only illustrate the order of gene expression attributed to genome
      reduction and steady cellular state but also indicate that the accessory
      sequences acquired during genome evolution largely participated in the
      coordination of transcriptomes to growth fitness.

PMID- 30294318
TI  - Accessory Toxins of Vibrio Pathogens and Their Role in Epithelial Disruption
      During Infection.
AB  - Gastrointestinal episodes associated with Vibrio species have been rising
      worldwide in the last few years. Consequently, it is important to comprehend how
      occurs the production of diarrhea, to establish new preventive and therapeutic
      measures. Besides the classical CT and TCP toxins, Zot, RTX, and Ace among others
      have been deeply studied in V. cholerae. However, in other Vibrio species of
      clinical interest, where some of these toxins have been reported, there is
      practically no information. Zot activates a cascade of signals inside of the cell
      that increase the permeability of epithelial barrier, while RTX causes
      depolymerization of the actin cytoskeleton and Ace increases the permeability of
      intestinal cell monolayers. The goal of this study is to acquire information
      about the distribution of these toxins in human pathogenic Vibrios and to review
      the progress in the study of their role in the intestinal epithelium during
      infection.

PMID- 30294320
TI  - Functional Characterization of Cryptococcal Genes: Then and Now.
AB  - Site-directed mutagenesis enables researchers to switch a gene of interest off
      for functional characterization of the gene. In the pathogenic yeasts,
      Cryptococcus neoformans and sister species C. deneoformans, this is almost
      exclusively achieved by introducing DNA into cells through either biolistic
      transformation or electroporation. The targeted gene is then disrupted by
      homologous recombination (HR) between the gene and the transforming DNA. Both
      techniques have downsides; biolistic transformation equipment is very expensive,
      limiting the use thereof to well-resourced laboratories, and HR occurs at
      extremely low frequencies in electroporated cryptococcal cells, making this
      method unappealing for gene targeting when not making use of additional
      modifications or methods to enhance HR in these cells. One approach to increase
      the frequency of HR in electroporated cryptococcal cells have recently been
      described. In this approach, CRISPR-Cas9 technology is utilized to form a double
      strand break in the targeted gene where after the occurrence of HR seems to be
      higher. The less expensive electroporation technique can therefore be used to
      deliver the CRISPR-Cas9 components into cells to disrupt a gene of interest, but
      only if the CRISPR components can be maintained for long enough in cells to
      enable their expression. Maintenance of episomal DNA occurs readily in C.
      deneoformans, but only under certain conditions in C. neoformans. In addition,
      CRISPR-Cas9 allows for gene complementation in order to fulfill Falkow's
      molecular Koch's postulates and adds other novel methods for studying genes as
      well, such as the addition of a fluorophore to an inactive Cas9 enzyme to
      highlight the location of a gene in a chromosome. These developments add less
      expensive alternatives to current methods, which could lead to more research on
      this yeast in developing countries where cryptococcal infections are more
      prevalent and researchers have access to more clinical isolates.

PMID- 30294321
TI  - Occurrence of Highly Conjugative IncX3 Epidemic Plasmid Carrying bla NDM in
      Enterobacteriaceae Isolates in Geographically Widespread Areas.
AB  - The emergence of New Delhi metallo-beta-lactamase (NDM) in common enterobacterial
      species is a major concern for healthcare. Early reports have revealed that the
      spread of NDM involved diverse and heterogeneous plasmids. Recently, the
      involvement of a rare, IncX3 subtype plasmid has been increasingly recognized.
      Here, we studied the prevalence of IncX plasmid subtypes in 198 carbapenem
      resistant Enterobacteriaceae, originating from a territory-wide active
      surveillance in Hong Kong in 2016. The complete sequences and biological features
      of the bla NDM-carrying plasmids were investigated. A total of 62 NDM-type, 21
      OXA-48 type, 14 IMP-type, 8 KPC-type, 4 IMI-type producers, and 89 non
      carbapenemase-producers were tested for presence of IncX subtypes. IncX3 (n = 60)
      was the most common subtype, followed by IncX4 (n = 6) and IncX1 (n = 2). The
      prevalence of IncX3 subtype in isolates producing NDM, other carbapenemase types
      and non-carbapenemase producers were 75.8, 21.3, and 3.4%, respectively (P <
      0.001). An IncX3 plasmid (size ~50 kb) was confirmed to carry bla NDM in 47
      isolates of different enterobacterial species. Thirteen IncX3 plasmids
      originating from six healthcare regions in Hong Kong were completely sequenced.
      The results showed that the IncX3 plasmids carrying bla NDM share a high degree
      of sequence identity with a previously reported plasmid, pNDM-HN380 (GenBank
      accession JX104760), over the backbone and genetic load regions. A blast search
      further revealed the occurrence of identical or nearly identical IncX3 plasmids
      carrying bla NDM in other part of China, Korea, Myanmar, India, Oman, Kuwait,
      Italy, and Canada. Two IncX3 carrying bla NDM were investigated further.
      Conjugation experiments demonstrated that the IncX3 plasmids could be efficiently
      transferred to multiple enterobacterial species at frequencies that are
      comparable or higher than the epidemic IncFII plasmid carrying bla CTX-M (pHK01).
      In addition, efficient transfer of the NDM plasmids occurred over a range of
      temperatures. In conclusion, this study demonstrated the important role played by
      IncX3 in the dissemination of NDM and the occurrence of pNDM-HN380-like plasmids
      in geographically widespread areas. The high mobility of IncX3 plasmid across
      different enterobacterial species highlights the ability of this plasmid replicon
      to be an important vehicle in worldwide dissemination of NDM.

PMID- 30294324
TI  - A Novel Antigen-Sampling Cell in the Teleost Gill Epithelium With the Potential
      for Direct Antigen Presentation in Mucosal Tissue.
AB  - In mammals, M cells can take up antigens through mucosal surfaces of the gut and
      the respiratory tract. Since M cells are deficient of lysosomes and phagosomes,
      the antigens are directly delivered to the mucosa-associated lymphoid tissue
      (MALT) without degradation. In teleost fish, the entire body surface (gills,
      skin, and intestinal system) is covered by mucus; however, specific antigen
      sampling cells have not yet been identified in their mucosal tissues. Here, we
      show that two phenotypes of antigen-sampling cells take up antigens through
      epithelial surfaces of the rainbow trout gill. One phenotype of antigen-sampling
      cells has features of monocyte/macrophage/dendritic cell-type cells; they have
      large vacuoles in the cytoplasm and express PTPRC (CD45), CD83, IL-1beta, and IL
      12p40b. The second phenotype exhibits similar characteristics to mammalian M
      cells; the corresponding cells bind the lectin UEA-1 but not WGA and show
      expression of M cell marker gene Anxa5. In contrast to mammalian M cells, teleost
      M-type cells were found to exhibit small vacuoles in their cytoplasm and to
      express almost all genes related to the "phagosome", "lysosome," and "antigen
      processing and presentation" pathways. Furthermore, MHC class II was
      constitutively expressed on a fraction of M-type cells, and this expression was
      significantly increased after antigen uptake, suggesting that the MHC class II is
      inducible by antigen stimulation. Here, we suggest that teleost M-type cells play
      a role in the phylogenetically primitive teleost immune system, similar to bona
      fide M cells. In addition, the presence of MHC class II expression suggests an
      additional role in antigen presentation in the gills, which are an organ with
      high T cell abundance, especially in interbranchial lymphoid tissue. The present
      results suggest an unconventional antigen presentation mechanism in the primitive
      mucosal immune system of teleosts, which generally lack highly organized lymphoid
      tissues. Moreover, the results of this work may be valuable for the development
      of mucosal vaccines that specifically target M-type cells; mucosal vaccines
      significantly reduce working costs and the stress that is usually induced by
      vaccination via injection of individual fish.

PMID- 30294325
TI  - Anaphylatoxin Receptors C3aR and C5aR1 Are Important Factors That Influence the
      Impact of Ethanol on the Adipose Secretome.
AB  - Background and aims: Chronic ethanol exposure results in inflammation in adipose
      tissue; this response is associated with activation of complement as well as the
      development of alcohol-related liver disease (ALD). Adipose communicates with
      other organs, including liver, via the release of soluble mediators, such as
      adipokines and cytokines, characterized as the "adipose secretome." Here we
      investigated the role of the anaphaylatoxin receptors C3aR and C5aR1 in the
      development of adipose tissue inflammation and regulation of the adipose
      secretome in murine ALD (mALD). Methods: Wild-type C57BL/6 (WT), C3aR -/-, and
      C5aR1 -/- mice were fed Lieber-DeCarli ethanol diet for 25 days (6% v/v, 32%
      kcal) or isocaloric control diets; indicators of inflammation and injury were
      assessed in gonadal adipose tissue. The adipose secretome was characterized in
      isolated adipocytes and stromal vascular cells. Results: Ethanol feeding
      increased the expression of adipokines, chemokines and leukocyte markers in
      gonadal adipose tissue from WT mice; C3aR -/- were partially protected while
      C5aR1 -/- mice were completely protected. In contrast, induction of CYP2E1 and
      accumulation of TUNEL-positive cells in adipose in response to ethanol feeding
      was independent of genotype. Bone marrow chimeras, generated with WT and C5aR1 -/
      mice, revealed C5aR1 expression on non-myeloid cells, likely to be adipocytes,
      contributed to ethanol-induced adipose inflammation. Chronic ethanol feeding
      regulated both the quantity and distribution of adipokines secreted from
      adipocytes in a C5aR1-dependent mechanism. In WT mice, chronic ethanol feeding
      induced a predominant release of pro-inflammatory adipokines from adipocytes,
      while the adipose secretome from C5aR1 -/- mice was characterized by an anti
      inflammatory/protective profile. Further, the cargo of adipocyte-derived
      extracellular vesicles (EVs) was distinct from the soluble secretome; in WT EVs,
      ethanol increased the abundance of pro-inflammatory mediators while EV cargo from
      C5aR1 -/- adipocytes contained a greater diversity and more robust expression of
      adipokines. Conclusions: C3aR and C5aR1 are potent regulators of ethanol-induced
      adipose inflammation in mALD. C5aR1 modulated the impact of chronic ethanol on
      the content of the adipose secretome, as well as influencing the cargo of an
      extensive array of adipokines from adipocyte-derived EVs. Taken together, our
      data demonstrate that C5aR1 contributes to ethanol-mediated changes in the
      adipose secretome, likely contributing to intra-organ injury in ALD.

PMID- 30294323
TI  - Going to Bat(s) for Studies of Disease Tolerance.
AB  - A majority of viruses that have caused recent epidemics with high lethality rates
      in people, are zoonoses originating from wildlife. Among them are filoviruses
      (e.g., Marburg, Ebola), coronaviruses (e.g., SARS, MERS), henipaviruses (e.g.,
      Hendra, Nipah) which share the common features that they are all RNA viruses, and
      that a dysregulated immune response is an important contributor to the tissue
      damage and hence pathogenicity that results from infection in humans.
      Intriguingly, these viruses also all originate from bat reservoirs. Bats have
      been shown to have a greater mean viral richness than predicted by their
      phylogenetic distance from humans, their geographic range, or their presence in
      urban areas, suggesting other traits must explain why bats harbor a greater
      number of zoonotic viruses than other mammals. Bats are highly unusual among
      mammals in other ways as well. Not only are they the only mammals capable of
      powered flight, they have extraordinarily long life spans, with little detectable
      increases in mortality or senescence until high ages. Their physiology likely
      impacted their history of pathogen exposure and necessitated adaptations that may
      have also affected immune signaling pathways. Do our life history traits make us
      susceptible to generating damaging immune responses to RNA viruses or does the
      physiology of bats make them particularly tolerant or resistant? Understanding
      what immune mechanisms enable bats to coexist with RNA viruses may provide
      critical fundamental insights into how to achieve greater resilience in humans.

PMID- 30294327
TI  - Functional Inhibitory Siglec-6 Is Upregulated in Human Colorectal Cancer
      Associated Mast Cells.
AB  - Mast cells (MC) accumulate in colorectal cancer (CRC) and the relationship
      between MC density and cancer progression has been well recognized. MC can be
      either pro-tumor or anti-tumor players, depending on the local factors present in
      the tumor microenvironment. Upon malignant transformation, cancer cells express
      high levels of sialic acids on cell membrane or by secretion. Siglecs are a
      family of immunoglobulin-like receptors that bind sialic acids and each subtype
      has a distinct pattern of expression on immune cells. Among them, Siglec-6 is
      expressed predominately by MC. However, the function of Siglec-6 in MC is largely
      unexplored and whether it is expressed by CRC-associated MC remains unknown. In
      this study, we explored the function of Siglec-6 in CD34+ derived human MC. MC
      activation was initiated by IgE crosslinking with or without preincubation of
      anti-Siglec-6 Ab. Siglec-6 engagement significantly attenuated IgE-dependent MC
      degranulation as measured by beta-hexosaminidase release and CD63 expression.
      Interestingly, the production of GM-CSF was also shown reduced upon Siglec-6
      engagement. To mimic the milieu of CRC, we cultured primary human MC with colon
      cancer cells or under hypoxia and Siglec-6 was then measured on these conditioned
      MC. Coculture with colon cancer cells (HT29 and Caco2) induced upregulation of
      Siglec-6 on MC. In comparison, normal colon cells (CCD841) had no effect. Also, a
      time-dependent increase of Siglec-6 by MC was observed under 1% O2.
      Immunohistochemistry of CRC tissue showed expression of Siglec-6 by MC in
      submucosa. Lectin immunochemistry revealed the presence of actual ligands for
      Siglec-6 in human CRC tissues. Together, our findings illustrate that Siglec-6 is
      a functionally inhibitory receptor on MC and suggest that Siglec-6 expression may
      be relevant for MC activity in the tumor microenvironment of CRC.

PMID- 30294326
TI  - CD38 Antibodies in Multiple Myeloma: Mechanisms of Action and Modes of
      Resistance.
AB  - MM cells express high levels of CD38, while CD38 is expressed at relatively low
      levels on normal lymphoid and myeloid cells, and in some non-hematopoietic
      tissues. This expression profile, together with the role of CD38 in adhesion and
      as ectoenzyme, resulted in the development of CD38 antibodies for the treatment
      of multiple myeloma (MM). At this moment several CD38 antibodies are at different
      phases of clinical testing, with daratumumab already approved for various
      indications both as monotherapy and in combination with standards of care in MM.
      CD38 antibodies have Fc-dependent immune effector mechanisms, such as complement
      dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC),
      and antibody-dependent cellular phagocytosis (ADCP). Inhibition of ectoenzymatic
      function and direct apoptosis induction may also contribute to the efficacy of
      the antibodies to kill MM cells. The CD38 antibodies also improve host-anti-tumor
      immunity by the elimination of regulatory T cells, regulatory B cells, and
      myeloid-derived suppressor cells. Mechanisms of primary and/or acquired
      resistance include tumor-related factors, such as reduced cell surface expression
      levels of the target antigen and high levels of complement inhibitors (CD55 and
      CD59). Differences in frequency or activity of effector cells may also contribute
      to differences in outcome. Furthermore, the microenvironment protects MM cells to
      CD38 antibody-induced ADCC by upregulation of anti-apoptotic molecules, such as
      survivin. Improved understanding of modes of action and mechanisms of resistance
      has resulted in rationally designed CD38-based combination therapies, which will
      contribute to further improvement in outcome of MM patients.

PMID- 30294328
TI  - Avelumab, an IgG1 anti-PD-L1 Immune Checkpoint Inhibitor, Triggers NK Cell
      Mediated Cytotoxicity and Cytokine Production Against Triple Negative Breast
      Cancer Cells.
AB  - The standard treatment for Triple Negative Breast Cancer (TNBC) patients is
      cytotoxic chemotherapy, but it is restricted since the duration of response is
      usually short. Blocking the PD-1/PD-L1 pathway through monoclonal antibodies
      (mAbs) appears to be a promising therapeutic strategy for TNBC patients. Avelumab
      is a human IgG1 anti-PD-L1 mAb being tested in clinical trials that may also
      trigger antibody-dependent cell-mediated cytotoxicity (ADCC) against cancer cells
      as an additional antitumor activity. In the present work, we studied in vitro
      Avelumab-mediated ADCC against a panel of TNBC cells with different PD-L1
      expression using peripheral blood mononuclear cells (PBMC) or purified NK cells
      from healthy donors. We determined that Avelumab significantly enhanced NK-cell
      mediated cytotoxicity against TNBC cells and that tumor cells expressing higher
      levels of PD-L1 were more sensitive to Avelumab-mediated ADCC. IFN-gamma
      treatment upregulated PD-L1 expression in tumor cells but had a variable impact
      on Avelumab-mediated ADCC, which could be related to the simultaneous effect of
      IFN-gamma on the expression of NK cell ligands. Moreover, IL-2 and IL-15
      stimulation of NK cells enhanced Avelumab-triggered cytokine production and
      degranulation along with increased lytic activity against tumor cells. Improving
      the treatment of TNBC remains still a considerable challenge. This in vitro study
      suggests that Avelumab-mediated ADCC, independently of the blockade of the PD
      1/PD-L1 pathway, could be a valuable mechanism for tumor cell elimination in
      TNBC. Avelumab combination with immunomodulators such as IL-15 or IL-2 could be
      taken into consideration to increase the therapeutic efficacy of Avelumab in
      TNBC.

PMID- 30294322
TI  - Genetic Alterations of TRAF Proteins in Human Cancers.
AB  - The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of
      cytoplasmic adaptor proteins regulate the signal transduction pathways of a
      variety of receptors, including the TNF-R superfamily, Toll-like receptors
      (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and cytokine
      receptors. TRAF-dependent signaling pathways participate in a diverse array of
      important cellular processes, including the survival, proliferation,
      differentiation, and activation of different cell types. Many of these TRAF
      dependent signaling pathways have been implicated in cancer pathogenesis. Here we
      analyze the current evidence of genetic alterations of TRAF molecules available
      from The Cancer Genome Atlas (TCGA) and the Catalog of Somatic Mutations in
      Cancer (COSMIC) as well as the published literature, including copy number
      variations and mutation landscape of TRAFs in various human cancers. Such
      analyses reveal that both gain- and loss-of-function genetic alterations of
      different TRAF proteins are commonly present in a number of human cancers. These
      include pancreatic cancer, meningioma, breast cancer, prostate cancer, lung
      cancer, liver cancer, head and neck cancer, stomach cancer, colon cancer, bladder
      cancer, uterine cancer, melanoma, sarcoma, and B cell malignancies, among others.
      Furthermore, we summarize the key in vivo and in vitro evidence that demonstrates
      the causal roles of genetic alterations of TRAF proteins in tumorigenesis within
      different cell types and organs. Taken together, the information presented in
      this review provides a rationale for the development of therapeutic strategies to
      manipulate TRAF proteins or TRAF-dependent signaling pathways in different human
      cancers by precision medicine.

PMID- 30294329
TI  - Systemic ST6Gal-1 Is a Pro-survival Factor for Murine Transitional B Cells.
AB  - Humoral immunity depends on intrinsic B cell developmental programs guided by
      systemic signals that convey physiologic needs. Aberrant cues or their improper
      interpretation can lead to immune insufficiency or a failure of tolerance and
      autoimmunity. The means by which such systemic signals are conveyed remain poorly
      understood. Hence, further insight is essential to understanding and treating
      autoimmune diseases and to the development of improved vaccines. ST6Gal-1 is a
      sialyltransferase that constructs the alpha2,6-sialyl linkage on cell surface and
      extracellular glycans. The requirement for functional ST6Gal-1 in the development
      of humoral immunity is well documented. Canonically, ST6Gal-1 resides within the
      intracellular ER-Golgi secretory apparatus and participates in cell-autonomous
      glycosylation. However, a significant pool of extracellular ST6Gal-1 exists in
      circulation. Here, we segregate the contributions of B cell intrinsic and
      extrinsic ST6Gal-1 to B cell development. We observed that B cell-intrinsic
      ST6Gal-1 is required for marginal zone B cell development, while B cell non
      autonomous ST6Gal-1 modulates B cell development and survival at the early
      transitional stages of the marrow and spleen. Exposure to extracellular ST6Gal-1
      ex vivo enhanced the formation of IgM-high B cells from immature precursors, and
      increased CD23 and IgM expression. Extrinsic sialylation by extracellular ST6Gal
      1 augmented BAFF-mediated activation of the non-canonical NF-kB, p38 MAPK, and
      PI3K/AKT pathways, and accelerated tyrosine phosphorylation after B cell receptor
      stimulation. in vivo, systemic ST6Gal-1 did not influence homing of B cells to
      the spleen but was critical for their long-term survival and systemic IgG levels.
      Circulatory ST6Gal-1 levels respond to inflammation, infection, and malignancy in
      mammals, including humans. In turn, we have shown previously that systemic ST6Gal
      1 regulates inflammatory cell production by modifying bone marrow myeloid
      progenitors. Our data here point to an additional role of systemic ST6Gal-1 in
      guiding B cell development, which supports the concept that circulating ST6Gal-1
      is a conveyor of systemic cues to guide the development of multiple branches of
      immune cells.

PMID- 30294331
TI  - Role of Matrix Metalloproteinase-2 in Eosinophil-Mediated Airway Remodeling.
AB  - Airway remodeling is responsible for the progressive decline of lung function in
      bronchial asthma. Matrix metalloproteinase-2 and fibroblast-to-myofibroblast
      transition are involved in tissue remodeling. Here we evaluated whether
      eosinophils play a role in fibroblasts-to-myofibroblasts transition and in the
      expression of matrix metalloproteinase-2. We co-cultured human eosinophils with
      human fetal lung fibroblast-1 cells, assessed the expression of remodeling
      associated molecules by immunoassays and polymerase-chain reaction, and
      eosinophils-mediated migration of human fetal lung fibroblast-1 cells using a
      Boyden chamber. To clarify the participation of matrix metalloproteinase-2 in
      airway remodeling we administered bone marrow-derived eosinophils by intra
      tracheal route to transgenic mice overexpressing the human matrix
      metalloproteinase-2. The expression of alpha-smooth muscle actin significantly
      increased in human fetal lung fibroblast-1 cells co-cultured with human
      eosinophils compared to controls. There was enhanced expression of matrix
      metalloproteinase-2 during fibroblast-to-myofibroblast transition. An inhibitor
      of matrix metalloproteinases blocked eosinophils-associated fibroblast-to
      myofibroblast transition and increased migration of fibroblasts. The human matrix
      metalloproteinase-2 transgenic mice receiving adoptive transfer of mouse
      eosinophils exhibited increased inflammation and advanced airway remodeling
      compared to wild type mice. This study demonstrated that eosinophils induce
      fibroblast-to-myofibroblast transition, secretion of matrix metalloproteinase-2,
      accelerated migration of fibroblasts, and promote matrix metalloproteinase-2
      related airway remodeling. These findings provide a novel mechanistic pathway for
      eosinophil-associated airway remodeling in bronchial asthma.

PMID- 30294330
TI  - The Role of Complement Activating Collectins and Associated Serine Proteases in
      Patients With Hematological Malignancies, Receiving High-Dose Chemotherapy, and
      Autologous Hematopoietic Stem Cell Transplantations (Auto-HSCT).
AB  - We conducted a prospective study of 312 patients (194 with multiple myeloma, 118
      with lymphomas) receiving high-dose conditioning chemotherapy and autologous
      hematopoietic stem cell transplantation (auto-HSCT). Polymorphisms of MBL2 and
      MASP2 genes were investigated and serial measurements of serum concentrations of
      mannose-binding lectin (MBL), CL-LK collectin and MASP-2 as well as activities of
      MBL-MASP-1 and MBL-MASP-2 complex were made. Serum samples were taken before
      conditioning chemotherapy, before HSCT and once weekly after (totally 4-5
      samples); in minority of subjects also 1 and/or 3 months post transplantation.
      The results were compared with data from 267 healthy controls and analyzed in
      relation to clinical data to explore possible associations with cancer and with
      chemotherapy-induced medical complications. We found a higher frequency of MBL
      deficiency-associated genotypes (LXA/O or O/O) among multiple myeloma patients
      compared with controls. It was however not associated with hospital infections or
      post-HSCT recovery of leukocytes, but seemed to be associated with the most
      severe infections during follow-up. Paradoxically, high MBL serum levels were a
      risk factor for prolonged fever and some infections. The first possible
      association of MBL2 gene 3'-untranslated region polymorphism with cancer
      (lymphoma) in Caucasians was noted. Heterozygosity for MASP2 gene +359 A>G
      mutation was relatively frequent in lymphoma patients who experienced bacteremia
      during hospital stay. The median concentration of CL-LK was higher in myeloma
      patients compared with healthy subjects. Chemotherapy induced marked increases in
      serum MBL and MASP-2 concentrations, prolonged for several weeks and relatively
      slighter decline in CL-LK level within 1 week. Conflicting findings on the
      influence of MBL on infections following chemotherapy of myeloma and lymphoma
      have been reported. Here we found no evidence for an association between MBL
      deficiency and infection during the short period of neutropenia following
      conditioning treatment before HSCT. However, we noted a possible protective
      effect of MBL during follow-up, and suspected that to be fully effective when
      able to act in combination with phagocytic cells after their recovery.

PMID- 30294332
TI  - Anti-glucocorticoid-induced Tumor Necrosis Factor-Related Protein (GITR) Therapy
      Overcomes Radiation-Induced Treg Immunosuppression and Drives Abscopal Effects.
AB  - Despite the potential to cure metastatic disease, immunotherapy on its own often
      fails outright or early on due to tumor immune evasion. To address this obstacle,
      we investigated combinations of anti-GITR, anti-PD1 and radiation therapy (XRT)
      in our previously developed anti-PD1 resistant 344SQ non-small cell lung
      adenocarcinoma preclinical tumor model. We hypothesized that targeting multiple
      mechanisms of immune evasion with this triple therapy would lead to an enhanced
      tumor-specific immune response and improve survival more so than any mono- or
      dual therapy. In a two tumor 344SQR murine model, treatment with anti-GITR, anti
      PD1, and XRT led to significantly improved survival and an abscopal response,
      with half of the mice becoming tumor free. These mice showed durable response and
      increased CD4+ and CD8+ effector memory on tumor rechallenge. Regulatory T cells
      (Tregs) expressed the highest level of GITR at the tumor site and anti-GITR
      therapy drastically diminished Tregs at the tumor site. Anti-tumor effects were
      largely dependent on CD4+ T cells and partially dependent on CD8+ T cells. Anti
      GITR IgG2a demonstrated superior efficacy to anti-GITR IgG1 in driving antitumor
      effects. Collectively, these results suggest that combinatorial strategies
      targeting multiple points of tumor immune evasion may lead to a robust and
      lasting antitumor response.

PMID- 30294333
TI  - Effect of Soil pH on the Growth, Reproductive Investment and Pollen Allergenicity
      of Ambrosia artemisiifolia L.
AB  - Despite the importance of soil reaction for alien plant establishment, few and
      incomplete studies have included this key factor so far. In this study, we
      investigated the effects of soil pH on the germination, growth (plant height,
      width, dry weight, etc.) and reproductive investment (inflorescence size and n
      degrees  of flowers) of Ambrosia artemisiifolia (common ragweed), an allergenic
      species that is highly invasive and alien in Europe, through a replicated
      experiment in controlled conditions. In addition, we determined if soil pH has an
      effect on the total pollen allergenicity of the species. After preliminary
      germination tests on agar at different pH (from pH4 to pH8), plants were grown in
      natural soils with pH values of 5 (acid), 6 (sub-acid) and 7 (neutral) obtained
      by modifying a natural soil by liming methods (calcium hydroxide solution).
      Results showed that plants grown at pH7 were shorter and developed leaves at a
      slower rate than those grown at pH5 and pH6; plants grown at pH7 did not produce
      flowers and pollen. We also observed that, at pH5 and pH6, larger plants (as
      assessed by the dry weight of the aerial biomass) had both larger and more
      numerous inflorescences and emitted pollen earlier. Finally, the IgE-binding
      signal was higher in pollen samples collected from plants grown at pH5
      (Integrated Optical Density, IOD, range: 1.12-1.25) than in those grown at pH6
      (IOD range: 0.86 -1.03). Although we acknowledge the limitations of only testing
      the effects of pH in controlled conditions, this study suggests that soil pH
      greatly affects the growth and development of A. artemisiifolia and indicates
      that it may have a role in limiting the distribution and hazardousness of this
      plant. Future field tests should therefore assess the effectiveness of liming in
      the management and control of ragweed and other alien species.

PMID- 30294334
TI  - Identification of the Bisabolol Synthase in the Endangered Candeia Tree
      (Eremanthus erythropappus (DC) McLeisch).
AB  - Candeia (Eremanthus erythropappus (DC) McLeisch, Asteraceae) is a Brazilian tree,
      mainly occurring in the cerrado areas. From ethnobotanical information its
      essential oil is known to have wound healing and nociceptive properties. These
      properties are ascribed to result from a sesquiterpene alcohol, (-)-alpha
      bisabolol, which is present at high concentrations in this oil. Bisabolol is
      highly valued by the cosmetic industry because of its antibacterial, anti
      inflammatory, skin-smoothing and wound healing properties. Over the past decades,
      Candeia timber has been collected at large scale for bisabolol extraction from
      wild reserves and the species is thereby at risk of extinction. To support the
      development of breeding and nursing practices that would facilitate sustainable
      cultivation of Candeia, we identified a terpene synthase gene, EeBOS1, that
      appears to control biosynthesis (-)-alpha-bisabolol in the plant. Expression of
      this gene in E. coli showed that EeBOS1 protein is capable of producing (-)-alpha
      bisabolol from farnesyl pyrophosphate in vitro. Analysis of gene expression in
      different tissues from Candeia plants in different life stages showed a high
      correlation of EeBOS1 expression and accumulation of (-)-alpha-bisabolol. This
      work is the first step to unravel the pathway toward (-)-alpha-bisabolol in
      Candeia, and in the further study of the control of (-)-alpha-bisabolol
      production.

PMID- 30294335
TI  - Genome-Wide Association Mapping in a Rice MAGIC Plus Population Detects QTLs and
      Genes Useful for Biofortification.
AB  - The development of rice genotypes with micronutrient-dense grains and disease
      resistance is one of the major priorities in rice improvement programs. We
      conducted Genome-wide association studies (GWAS) using a Multi-parent Advanced
      Generation Inter-Cross (MAGIC) Plus population to identify QTLs and SNP markers
      that could potentially be integrated in biofortification and disease resistance
      breeding. We evaluated 144 MAGIC Plus lines for agronomic and biofortification
      traits over two locations for two seasons, while disease resistance was screened
      for one season in the screen house. X-ray fluorescence technology was used to
      measure grain Fe and Zn concentrations. Genotyping was carried out by genotype by
      sequencing and a total of 14,242 SNP markers were used in the association
      analysis. We used Mixed linear model (MLM) with kinship and detected 57
      significant genomic regions with a -log10 (P-value) >= 3.0. The PH 1.1 and Zn 7.1
      were consistently identified in all the four environments, ten QTLs qDF 3.1, qDF
      6.2 qDF 9.1 qPH 5.1 qGL 3.1, qGW 3.1, qGW 11.1, and qZn 6.2 were detected in two
      environments, while two major loci qBLB 11.1 and qBLB 5.1 were identified for
      Bacterial Leaf Blight (BLB) resistance. The associated SNP markers were found to
      co-locate with known major genes and QTLs such as OsMADS50 for days to flowering,
      osGA20ox2 for plant height, and GS3 for grain length. Similarly, Xa4 and xa5
      genes were identified for BLB resistance and Pi5(t), Pi28(t), and Pi30(t) genes
      were identified for Blast resistance. A number of metal homeostasis genes OsMTP6,
      OsNAS3, OsMT2D, OsVIT1, and OsNRAMP7 were co-located with QTLs for Fe and Zn. The
      marker-trait relationships from Bayesian network analysis showed consistency with
      the results of GWAS. A number of promising candidate genes reported in our study
      can be further validated. We identified several QTLs/genes pyramided lines with
      high grain Zn and acceptable yield potential, which are a good resource for
      further evaluation to release as varieties as well as for use in breeding
      programs.

PMID- 30294336
TI  - Cloning and Characterization of TpNRAMP3, a Metal Transporter From Polish Wheat
      (Triticum polonicum L.).
AB  - Essential transition metals and non-essential metals often co-exist in arable
      soils. In plants, some transition metal transporters, such as the natural
      resistance-associated macrophage proteins (NRAMPs), poorly selectively transport
      metals with similar chemical properties whether they are essential or non
      essential. In this study, a member of the NRAMP transporter family, TpNRAMP3, was
      identified from dwarf Polish wheat (Triticum polonicum L.). TpNRAMP3 encodes a
      plasma membrane-localized protein and was highly expressed in leaf blades and
      roots at the jointing and booting stages, and in the first nodes at the grain
      filling stage. Expression of TpNRAMP3 increased sensitivity to Cd and Co, but not
      Zn, and increased the Cd and Co concentrations in yeast. TpNRAMP3 expression in
      Arabidopsis increased concentrations of Cd, Co, and Mn, but not Fe or Zn, in
      roots, shoots, and whole plant. However, TpNRAMP3 did not affect translocation of
      Cd, Co, or Mn from roots to shoots. These results suggest that TpNRAMP3 is a
      transporter for Cd, Co, and Mn accumulation, but not for Fe or Zn. However, Cd
      and Co are non-essential toxic metals; selective genetic manipulation of TpNRAMP3
      will help breed low Cd- and Co-accumulating cultivars.

PMID- 30294338
TI  - Overexpression of RsMYB1 Enhances Anthocyanin Accumulation and Heavy Metal Stress
      Tolerance in Transgenic Petunia.
AB  - The RsMYB1 transcription factor (TF) controls the regulation of anthocyanin in
      radishes (Raphanus sativus), and its overexpression in tobacco and petunias
      strongly enhances anthocyanin production. However, there are no data on the
      involvement of RsMYB1 in the mechanisms underlying abiotic stress tolerance,
      despite strong sequence similarity with other MYBs that confer such tolerance. In
      this study, we used the anthocyanin-enriched transgenic petunia lines PM6 and
      PM2, which overexpress RsMYB1. The tolerance of these lines to heavy metal stress
      was investigated by examining several physiological and biochemical factors, and
      the transcript levels of genes related to metal detoxification and antioxidant
      activity were quantified. Under normal conditions (control conditions),
      transgenic petunia plants (T2-PM6 and T2-PM2) expressing RsMYB1, as well as wild
      type (WT) plants, were able to thrive by producing well-developed broad leaves
      and regular roots. In contrast, a reduction in plant growth was observed when
      these plants were exposed to heavy metals (CuSO4, ZnSO4, MnSO4, or K2Cr2O7).
      However, T2-PM6 and T2-PM2 were found to be more stress tolerant than the WT
      plants, as indicated by superior results in all analyzed parameters. In addition,
      RsMYB1 overexpression enhanced the expression of genes related to metal
      detoxification [glutathione S-transferase (GST) and phytochelatin synthase (PCS)]
      and antioxidant activity [superoxide dismutase (SOD), catalase (CAT), and
      peroxidase (POX)]. These results suggest that enhanced expression levels of the
      above genes can improve metal detoxification activities and antioxidant activity,
      which are the main components of defense mechanism included in abiotic stress
      tolerance of petunia. Our findings demonstrate that RsMYB1 has potential as a
      dual-function gene that can have an impact on the improvement of anthocyanin
      production and heavy metal stress tolerance in horticultural crops.

PMID- 30294337
TI  - Genetic and Systematic Approaches Toward G Protein-Coupled Abiotic Stress
      Signaling in Plants.
AB  - Heterotrimeric G protein, composed of Galpha, Gbeta, and Ggamma subunits,
      modulates plant adaptations to environmental stresses such as high salinity,
      drought, extreme temperatures and high light intensity. Most of these evidence
      were however derived solely from conventional genetics methods with which stress
      associated phenotypes were compared between wild type and various G protein
      mutant plants. Recent advances in systematic approaches, mainly transcriptome and
      proteome, have contributed to in-depth understanding of molecular linkages
      between G proteins and environmental changes. Here, we update our knowledge on
      the roles of G proteins in abiotic stress responses. Furthermore, we highlight
      the current whole genome studies and integrated omics approach to better
      understand the fundamental G protein functions involved in abiotic stress
      responses. It is our purpose here to bridge the gap between molecular mechanisms
      in G protein science and stress biology and pave the way toward crop improvement
      researches in the future.

PMID- 30294339
TI  - Increased Gibberellins and Light Levels Promotes Cell Wall Thickness and Enhance
      Lignin Deposition in Xylem Fibers.
AB  - Light intensity and hormones (gibberellins; GAs) alter plant growth and
      development. A fine regulation triggered by light and GAs induces changes in stem
      cell walls (CW). Cross-talk between light-stimulated and GAs-induced processes as
      well as the phenolic compounds metabolism leads to modifications in lignin
      formation and deposition on cell walls. How these factors (light and GAs) promote
      changes in lignin content and composition. In addition, structural changes were
      evaluated in the stem anatomy of tobacco plants. GA3 was sprayed onto the leaves
      and paclobutrazol (PAC), a GA biosynthesis inhibitor, via soil, at different
      irradiance levels. Fluorescence microscopy techniques were applied to detect
      lignin, and electron microscopy (SEM and TEM) was used to obtain details on cell
      wall structure. Furthermore, determination of total lignin and monomer contents
      were analyzed. Both light and GAs induces increased lignin content and CW
      thickening as well as greater number of fiber-like cells but not tracheary
      elements. The assays demonstrate that light exerts a role in lignification under
      GA3 supplementation. In addition, the existence of an exclusive response
      mechanism to light was detected, that GAs are not able to replace.

PMID- 30294340
TI  - Cold Hardiness in Trees: A Mini-Review.
AB  - Significant advances have been made in our understanding of the regulation of
      cold hardiness. The existence of numerous biophysical and biochemical adaptive
      mechanisms in perennial woody plants and the complexity their regulation has made
      the development of methods for managing and improving cold hardiness in perennial
      woody plants has been very difficult. This may be partially attributed to viewing
      cold hardiness as a single dimensional response, rather than as a complex
      phenomenon, involving different mechanisms (avoidance and tolerance), different
      stages (mid-winter vs. late winter), and having an intimate overlap with the
      genetic regulation of dormancy. In particular separating the molecular regulation
      of cold hardiness from growth processes has been challenging. ICE and C-repeat
      binding factor (CBF), transcription factors (Inducer of CBF expression and CRT
      binding factor) have been shown to be an important aspect in the regulation of
      cold-induced gene expression. Evidence has emerged, however, that they are also
      intimately involved in the regulation of growth, flowering, dormancy, and
      stomatal development. This evidence includes the presence of CBF binding motifs
      in genes regulating these processes, or through cross-talk between the pathways
      that regulate them. Recent changes in climate that have resulted in erratic
      episodes of unseasonal warming followed by more seasonal patterns of low
      temperatures has also highlighted the need to better understand the genetic and
      molecular regulation of deacclimation, a topic of research that is only more
      recently being addressed. Environmentally-induced epigenetic regulation of stress
      responses and seasonal processes such as cold acclimation, deacclimation, and
      dormancy have been documented but are still poorly understood. Advances in the
      ability to efficiently generate large DNA and RNA datasets and genetic
      transformation technologies have greatly increased our ability to explore the
      regulation of gene expression and explore genetic diversity. Greater knowledge of
      the interplay between epigenetic and genetic regulation of cold hardiness, along
      with the application of advanced genetic analyses, such as genome-wide
      association-studies (GWAS), are needed to develop strategies for addressing the
      complex processes associated with cold hardiness in woody plants. A cautionary
      note is also indicated regarding the time-scale needed to examine and interpret
      plant response to freezing temperatures if progress is to be made in developing
      effective approaches for manipulating and improving cold hardiness.

PMID- 30294341
TI  - Differential Regulation of PIWI-LIKE 2 Expression in Primordial Germ Cell Tumor
      Cell Lines by Promoter Methylation.
AB  - PIWI-LIKE 2, a member of the ARGONAUTE protein family, is exclusively expressed
      in pre-pachytene and pachytene stages of spermatogenesis. PIWI-LIKE 2 acts in the
      germ cell development and the silencing of retrotransponsons to maintain the
      genomic integrity and stem cell character. In the present study we investigated
      DNA methylation as potential mechanism for the regulation of human PIWI-LIKE 2
      expression in cell lines related to spermatozoa precursor cells. We detected a
      high methylation of the PIWI-LIKE 2 promoter in TCam-2 cells, while in NT2/D1
      cells the promoter was hypomethylated. Concordantly, PIWI-LIKE 2 expression is
      higher in NT2/D1 cells than in TCam-2 cells. By demethylation of the promoter
      with 5'-Aza-2'-deoxycytidine, PIWI-LIKE 2 expression in TCam-2 was increased,
      while in NT2/D1 no alterations in PIWI-LIKE 2 expression could be detected. In
      conclusion, we analyzed the DNA methylation driving PIWI-LIKE 2 expression in
      undifferentiated germ cell tumors and demonstrated an epigenetic basis for PIWI
      LIKE 2 expression in this cell type.

PMID- 30294342
TI  - Lead Modulates trans- and cis-Expression Quantitative Trait Loci (eQTLs) in
      Drosophila melanogaster Heads.
AB  - Lead exposure has long been one of the most important topics in global public
      health because it is a potent developmental neurotoxin. Here, an eQTL analysis,
      which is the genome-wide association analysis of genetic variants with gene
      expression, was performed. In this analysis, the male heads of 79 Drosophila
      melanogaster inbred lines from Drosophila Synthetic Population Resource (DSPR)
      were treated with or without developmental exposure, from hatching to adults, to
      250 MUM lead acetate [Pb(C2H3O2)2]. The goal was to identify genomic intervals
      that influence the gene-expression response to lead. After detecting 1798 cis
      eQTLs and performing an initial trans-eQTL analysis, we focused our analysis on
      lead-sensitive "trans-eQTL hotspots," defined as genomic regions that are
      associated with a cluster of genes in a lead-dependent manner. We noticed that
      the genes associated with one of the 14 detected trans-eQTL hotspots, Chr 2L:
      6,250,000 could be roughly divided into two groups based on their differential
      expression profile patterns and different categories of function. This trans-eQTL
      hotspot validates one identified in a previous study using different recombinant
      inbred lines. The expression of all the associated genes in the trans-eQTL
      hotspot was visualized with hierarchical clustering analysis. Besides the overall
      expression profile patterns, the heatmap displayed the segregation of
      differential parental genetic contributions. This suggested that trans-regulatory
      regions with different genetic contributions from the parental lines have
      significantly different expression changes after lead exposure. We believe this
      study confirms our earlier study, and provides important insights to unravel the
      genetic variation in lead susceptibility in Drosophila model.

PMID- 30294343
TI  - Identification and Functional Analysis of Two New Mutant BnFAD2 Alleles That
      Confer Elevated Oleic Acid Content in Rapeseed.
AB  - Rapeseed (Brassica napus L.) is a vital oil crop worldwide. High oleic acid
      content is a desirable quality trait for rapeseed oil, which makes it more
      beneficial to human health. However, many germplasm resources with high oleic
      acid content in rapeseed have not been evaluated with regard to their genotypes,
      making it difficult to select the best strains with this trait for the breeding
      of high oleic acid rapeseed variety. This work was to explore the gene-regulation
      mechanism of this trait using a new super-high oleic acid content (~85%) line
      N1379T as genetic material. In this study, the sequences of four homologous fatty
      acid desaturase (BnFAD2) genes were compared between super-high (~85%, N1379T)
      and normal (~63%) oleic acid content lines. Results showed that there were two
      single-nucleotide polymorphisms (SNPs) in BnFAD2-1 and BnFAD2-2, respectively,
      which led to the amino acid changes (E106K and G303E) in the corresponding
      proteins. Functional analysis of both genes in yeast confirmed that these SNPs
      were loss-of-function mutations, thus limiting the conversion of oleic acid to
      linoleic acid and resulting in the considerable accumulation of oleic acid.
      Moreover, two specific cleaved amplified polymorphic sequences (CAPS) markers for
      the two SNPs were developed to identify genotypes of each line in the F2 and BC1
      populations. Furthermore, these two mutant loci of BnFAD2-1 and BnFAD2-2 genes
      were positively associated with elevated oleic acid levels and had a similar
      effect with regard to the increase of oleic acid content. Taken together, these
      two novel SNPs in two different BnFAD2 genes jointly regulated the high oleic
      acid trait in this special germplasm. The study provided insight into the genetic
      regulation involved in oleic acid accumulation and highlighted the use of new
      alleles of BnFAD2-1 and BnFAD2-2 in breeding high oleic acid rapeseed varieties.

PMID- 30294344
TI  - Taxonomically Restricted Genes Are Fundamental to Biology and Evolution.
AB  - Genes limited to particular clades, taxonomically restricted genes (TRGs), are
      common in all sequenced genomes. TRGs have recently become associated with the
      evolution of novelty, as numerous studies across the tree of life have now linked
      expression of TRGs with novel phenotypes. However, TRGs that underlie ancient
      lineage specific traits have been largely omitted from discussions of the general
      importance of TRGs. Here it is argued that when all TRGs are considered, it is
      apparent that TRGs are fundamental to biology and evolution and likely play many
      complementary roles to the better understood toolkit genes. Genes underlying
      photosynthesis and skeletons, for example, are examples of commonplace
      fundamental TRGs. Essentially, although basic cell biology has a highly conserved
      genetic basis across the tree of life, most major clades also have lineage
      specific traits central to their biology and these traits are often based on
      TRGs. In short, toolkit genes underlie what is conserved across organisms, while
      TRGs define in many cases what is unique. An appreciation of the importance of
      TRGs will improve our understanding of evolution by triggering the study of
      neglected topics in which TRGs are of paramount importance.

PMID- 30294345
TI  - Applicability of a shortened interpretation model for intraoperative parathyroid
      hormone monitoring in patients with primary hyperparathyroidism in an endemic
      goiter region.
AB  - Background: In primary hyperparathyroidism (pHPT), quick intraoperative
      parathyroid hormone monitoring (IOPTH) is performed to predict complete excision
      of hyperfunctioning tissue and therefore cure. In recent years, efforts have been
      made to make this prediction more accurate and to shorten the duration of the
      test, respectively, and therefore reduce waiting and total operating time. The
      aim of this study was to evaluate the practicability and safety of a time-reduced
      criterion (decline >= 35% after 5 min) in a large cohort of patients. Methods: In
      an 11-year period, all patients operated for pHPT were analyzed. After
      preoperative localization studies, hyperfunctioning parathyroid tissue was
      removed and IOPTH monitoring was performed. Intraoperatively, a decline of >=50%
      from baseline 10 min after excision of the gland predicted cure. The performance
      of an interpretation model, using an earlier PTH level was analyzed
      retrospectively (decline >= 35% from baseline 5 min after excision). Differences
      in sensitivity, specificity, positive/negative predictive value and accuracy were
      calculated. Results: According to the inclusion criteria, 1018 patients were
      analyzed. IOPTH predicted cure in 854 patients (83.9%) 10 min after gland
      excision with a false positive decline in 13 patients (1.5%). Applying the
      modified criterion (>=35% decline within 5 min), 814 patients (80%) showed an
      appropriate decline (false positive in 18 [2.2%]). Overall, multiple gland
      disease would have been missed in 7 patients. McNemar's test showed a
      significantly lower sensitivity, specificity and accuracy applying the "35%"
      criterion. Conclusions: In an endemic goiter region, a criterion, demanding a >=
      35% decline 5 min after excision can not be recommended for IOPTH monitoring in
      patients with pHPT.

PMID- 30294346
TI  - Is there any relationship between human foamy virus infections and familial
      Mediterranean fever?
AB  - Background: Familial Mediterranean fever (FMF) is generally defined as an
      autosomal recessive disease, characterized by the automatic activation of the
      innate immune system in the absence of a detectable pathogenic stimulant. We
      hypothesize that the pathogenic factors, besides the genetic causes, may affect
      the development of FMF symptoms. To test this hypothesis, we examined the effects
      of human foamy virus (HFV) positivity on the occurrence of the clinical symptoms
      of FMF. Materials and Methods: Two hundred and twenty-two FMF patients with
      definitive diagnosis according to Tel Hashomer criteria (study group 1 [SG1]),
      205 symptomatic FMF patients who had definitive diagnosis according to the same
      criteria but did not carry any of the 12 most commonly occurring MEFV gene
      mutations (study group 2 [SG2]), and 200 healthy individuals were included as
      control group (study group 3 [SG3]) in the study. The genetic analysis was
      applied in the Molecular Genetics Laboratory of the Department of Medical
      Biology, Faculty of Medicine, Ondokuz Mayis University. This study was designed
      as a case-control study. HFV positivity was tested by amplifying the HFV bel1
      gene sequence with polymerase chain reaction technique. Statistical analyses were
      conducted using SPSS version 23.0 software. Results: HFV positivity showed
      significant differences between the study groups (P = 0.002). While 43 (19.02%)
      of the 222 SG1 patients were positive for the HFV bel1 gene sequence, 33 (16.09%)
      of the 205 SG2 patients were positive for the same sequence. Only 15 (7.5%) of
      the SG3 participants were positive for the presence of HFV bel1 gene sequence.
      Conclusion: The results of our study suggested that HFV positivity can be a
      stimulant pathogenic factor of natural immune system which can cause the
      emergence of FMF symptoms.

PMID- 30294347
TI  - High seroprevalence of anti-Helicobacter pylori antibodies in patients with
      ventilator-associated pneumonia.
AB  - Background: The pathogenesis of ventilator-associated pneumonia (VAP) is not
      clearly known. Recently, the role of gastric bacterial colonization has been
      proposed. The role of gastric colonization with Helicobacter pylori in
      pathogenesis of VAP was determined by comparing the prevalence of H. pylori in
      patients with VAP and control participants. Materials and Methods: One hundred
      and eighteen mechanically ventilated patients were divided into two groups; 59
      participants with VAP and 59 without VAP. Serologic tests for H. pylori were
      registered. Results: Mean age in seropositive patients was significantly higher.
      About 71.2% in VAP group and 61.01% in controls were IgG seropositive (P = 0.24).
      IgM seropositivity was 23.73% versus 8.47% in VAPs and controls, respectively (P
      = 0.024). By increasing the time of intubation, more patients became seropositive
      for IgM (Pearson's correlation coefficient = 0.4, P = 0.002). Conclusion: IgM
      seropositivity and serum levels were significantly higher in VAP patients.
      Furthermore, by increasing the duration of intubation, serum levels for IgM
      increased significantly.

PMID- 30294348
TI  - Cancer trends in a province of Southwest of Iran, 2003-2016.
AB  - Background: Awareness of the trends of cancer incidence in each geographic region
      is an important. The aim of present study was to determine the incidence trends
      of cancer in Chaharmahal and Bakhtiari (Ch and B) province in Southwest of Iran.
      Materials and Methods: In this secondary data analysis, retrospective existing
      data were used from cancer registry reports in Ch and B in Southwest of Iran in
      2003-2016. Data on epidemiologic trend were analyzed using Joinpoint software
      package and annual percentage change (APC) with 95% confidence interval (95% CI)
      was computed. Results: Age-standardized incidence rate per 100,000 persons in the
      province in 2003 was 31.74 that increased to 147.14 in 2016. APC during 2003-2016
      was 12.58% (CI: 9.3-16) and significant, which was 10.22% (7.4-13.1) and 14.47%
      (10.2-18.9) in men and women, respectively. Incidence of the stomach, breast,
      colorectal, thyroid, lymph node, and ovarian cancers is increasing and the
      highest incidence was observed in two age groups of 25-34 and 55-64 years.
      Conclusion: In general, cancers are of increasing trend. Surveillance and
      monitoring the incidence of cancer and studying the causes of environmental or
      genetic in the cancer changes can help for cancer prevention and control.

PMID- 30294349
TI  - Effect of extracorporeal shock wave therapy on improving burn scar in patients
      with burnt extremities in Isfahan, Iran.
AB  - Background: Pathologic scarring is a common problem after burn injury that has
      functional and esthetic limitations. Conservative and surgical treatments
      available for these scars are not always satisfactory. Extracorporeal shock wave
      therapy (ESWT) is a noninvasive modality that has proven positive effects on burn
      scars and wound healing in few studies. This study was conducted to evaluate the
      effects of ESWT on improving burn scar in extremities. Materials and Methods:
      This study was a prospective quasi-experimental on burn patients with burn scar
      in their extremities that underwent ESWT sessions once a week for 6 weeks. For
      evaluating pain and itching, visual analog scale (VAS) and for scar appearance,
      Vancouver Scar Scale (VSS) were used. These scales were measured and compared at
      the beginning of the treatment, at the end of the treatment, and 1 and 3 months
      after the end of the intervention. Results: In this study, 17 patients were
      treated with ESWT with a mean age of 37.94 +/- 7.25 years that 47.1% of them were
      male. The mean of VAS score for pain and itching and VSS score were decreased
      significantly after the treatment and during follow-ups (All P < 0.001).
      Conclusion: ESWT can improve the pain, itching, and appearance of the burn scar
      in human extremities in burn patients.

PMID- 30294350
TI  - The prognostic values of beta-2 microglobulin for risks of cardiovascular events
      and mortality in the elderly patients with isolated systolic hypertension.
AB  - Background: The present study aimed to investigate the effects of serum beta-2
      microglobulin (B2M) on the risks of major cardiovascular events (MACEs) and all
      cause death in Chinese elderly isolated systolic hypertension (ISH) patients
      without severe renal insufficiency (estimated glomerular filtration rate [eGFR]
      <30 ml/min/1.73 m2). Materials and Methods: Serum B2M concentration, creatinine
      eGFR, and blood pressure variability were evaluated in 460 elderly patients (mean
      age, 82.6 years; 28 women) with ISH in this observational study. The Cox
      proportional hazard model was adopted to calculate adjusted hazard ratios (HRs)
      of risk factors for cardiovascular events and all-cause deaths. Results: During a
      median follow-up period of 37.6 months, 63 patients (13.7%) died, and 65 patients
      (14.1%) had MACEs. Multivariable analysis showed that the higher serum B2M
      concentration (B2M >=0.28 mg/dl) was an independent predictor of increased risk
      of MACEs (nonfatal acute myocardial infarction, acute heart failure, ischemic
      stroke, and cardiovascular deaths) and all-cause death (HR: 2.62, 95% confidence
      interval [CI]: 1.46-4.69, P = 0.001 and HR: 3.40, 95% CI: 1.78-6.48, P < 0.001,
      respectively) adjusting for other multiple confounders including creatinine-eGFR
      and cystatin C. In addition, blood pressure variability derived from ambulatory
      blood pressure measurement was not associated with incidence of MACEs and all
      cause mortality (P > 0.05). Conclusion: Our data suggest that serum B2M
      concentration may be individually associated with MACEs and all-cause death in
      elderly ISH patients without severe renal insufficiency even after adjusted for
      creatinine-eGFR and cystatin C.

PMID- 30294351
TI  - G6PD deficiency and aluminum phosphide poisoning.
AB  - Aluminum phosphide (ALP) poisoning is one of the fatal poisonings in the world.
      Hemolysis is a rare presentation of this poisoning. Here, we report an episode of
      hemolysis due to G6PD deficiency after ingestion of ALP and also the patient
      survived.

PMID- 30294352
TI  - One-anastomosis gastric bypass as an alternative procedure of choice in morbidly
      obese patients.
AB  - One-anastomosis gastric bypass is an attractive bariatric procedure. It is
      effective in weight loss and comorbidity resolution. It is a relatively simple
      and fast operation with low complication rates that make it a suitable option in
      super-obese individuals. Although not proven yet, there are some concerns about
      its long-term safety profile in terms of biliary reflux, marginal ulcer, and
      esophagogastric malignancy. In this article, we review the technique of this
      procedure and discuss about some practical surgical highlights. Furthermore, we
      overview studies performed about this procedure and compare it to some other well
      established bariatric operations, while providing a detailed study about the
      facts related to its outcomes and complications.

PMID- 30294353
TI  - Changes in the hemoglobin level after one unit of packed red blood cell
      transfusion in Intensive Care Unit patients.
AB  - Background: Blood transfusion is essential in severely ill patients whose
      hemoglobin (Hb) levels are low, but there are some factors that inhibit optimal
      increase in Hb. The aim of this study was to evaluate the amount of increase in
      Hb levels after packed red blood cell (PRBC) transfusions in the Intensive Care
      Unit (ICU) patients and its related factors. Materials and Methods: This cross
      sectional study included 124 patients admitted to the ICU, and needed PRBC
      transfusion. Demographic information, Hb on the 1st day of admission, blood
      volume transfusions during the 7 days, and the 7th day of admission Hb level were
      extracted from patients' records. Results: The average initial Hb level of
      patients was reported as 6.17 +/- 1.43 g/dl, and after administrating PRBC (4.23
      +/- 1.87 units during 7 days), the Hb level was 8.09 +/- 1.66 g/dl after 7 days
      (mean difference was 1.91 +/- 1.93, t = 11.06, P < 0.001). No significant
      differences were found between change in Hb level in the terms of age, gender,
      underlying illness, body mass index, hospitalization history, fever, and duration
      of hospitalization (P > 0.05). However, the mean increased Hb level in
      hospitalized patients with internal disorders was the lowest (0.25 g/dl, P =
      0.002). Conclusion: The results of our study showed that the increased Hb level
      based on one unit of received PRBC was low, especially in patients with internal.
      Therefore, based on high frequency of anemia in ICU patients and relative
      complications, physicians should pay attention to factors affecting Hb levels
      after PRBC transfusion such as medical history.

PMID- 30294354
TI  - The Papanicolaou Society of Cytopathology guidelines for respiratory cytology:
      Reproducibility of categories among observers.
AB  - Introduction: The Papanicolaou Society of Cytopathology (PSC) has developed a set
      of guidelines for reporting respiratory cytology. While the malignancy risk for
      each category is known, the interobserver reproducibility of these diagnostic
      categories has not been well described. Methods: Fifty-five cytologic specimens
      obtained by fine needle aspiration from the pulmonary nodules were independently
      reviewed by four board-certified cytopathologists and assigned to the diagnostic
      categories described by the PSC guidelines for respiratory specimens. Statistical
      analysis for diagnostic accuracy was performed for absolute agreement and chance
      corrected agreement (kappa). Differences in frequency of distribution of
      diagnoses between raters were assessed using the Kruskal-Wallis test. Results: No
      significant differences in distribution of scores by raters were observed. On
      average, the absolute agreement was 49.5% and the chance-corrected agreement
      (kappa) was 20%. 34.5% of interrater comparisons were in full agreement, and
      total lack of agreement between the four categories was found in 3% of cases.
      Combining the "suspicious for malignancy" category with the "malignant" category
      did not significantly alter interrater agreement statistics. Conclusions: The PSC
      categories showed only fair reproducibility among four cytopathologists.
      Agreement between raters was at best fair and did not improve significantly when
      the categories "suspicious for malignancy" and "malignant" were combined. The
      most common source of disagreement appeared to be between the categories
      "suspicious" and "malignant."

PMID- 30294355
TI  - Not all neck mass fine-needle aspirations with squamous cells are squamous cell
      carcinoma; report of a case of recurrent thyroid carcinoma with papillary and
      squamous components.
AB  - We report a case of a 65-year-old female who had a total thyroidectomy 12 years
      ago for papillary thyroid carcinoma (PTC) who presented with a recurrent thyroid
      bed mass. Fine-needle aspiration biopsy yielded malignant cells, consistent with
      squamous cell carcinoma (SCCa). Surgical resection was performed, and histologic
      evaluation of the mass showed mixed PTC and SCCa. The tumor cells were positive
      for BRAF V600E mutation. Thyroid carcinomas with admixed papillary carcinoma and
      SCCa are rare and are associated with aggressive behavior, high rates of
      metastasis, and poor outcomes. Although SCCa presenting as a neck mass is
      relatively common, clinical history and appropriate workup are essential for
      accurate diagnosis and determination of origin.

PMID- 30294356
TI  - Personality Traits in Fibromyalgia (FM): Does FM Personality Exists? A Systematic
      Review.
AB  - Introduction: Fibromyalgia (FM) is the second most common rheumatic disease with
      many effects on patient's quality of life. It has been described as a chronic
      condition characterized by widespread musculo-skeletal pain, sleep disorders and
      prominent fatigue. Regarding the role of personality factors in fibromyalgia,
      researchers have focused both on personality traits and psychopathological
      aspects showing inconsistent results. In particular, several studies have
      examined the role of alexithymia in FM patients, a trait of personality
      characterized by difficulty in identification, recognition and description of
      emotions and feelings, while others have focused on a specific type of
      personality, such as type D personality (distressed personality). Other studies
      investigated personality in FM patients referring to Cloninger's model, a
      psychobiological model of personality that includes both temperamental and
      character dimensions of personality. Analyzing scientific literature on this
      subject seems well suited to provide a critical review of the latest studies and
      their results. Methods: The method used for this review satisfies the Preferred
      Reporting Items for Systematic Review and Meta-Analyses (PRISMA). We identified
      PsycInfo and PubMed as databases for our research. Results: Personality is
      studied under many aspects and a reference model is not always present. Many
      studies underline high levels of alexithymia and type D personality in FM
      patients but when depression is controlled, these results do not differ from
      those of healthy controls. Conclusion: Studies that use a comprehensive model of
      personality present a different theoretical approach and use alternatively the
      Big-Five model, Eysenck's and Cloninger's models. The use of a comprehensive
      model of personality and the control of psychopathological disorders, such as
      anxiety and depression, seem to be very relevant for a better understanding of a
      specific personality profile associated with fibromyalgia.

PMID- 30294357
TI  - Exploring the Role of Sedentary Behavior and Physical Activity in Depression and
      Anxiety Symptom Severity among Patients with Substance Use Disorders.
AB  - Research has consistently shown that regular physical activity may protect
      against the development and maintenance of depression and anxiety, whereas
      sedentary behavior may exacerbate depression and anxiety. However, much of the
      past research in this area has focused on non-clinical populations. Therefore,
      the goal of this study was to examine the relations of physical activity and
      sedentary behavior to depression and anxiety symptom severity among an
      understudied patient population, patients in residential substance use disorder
      (SUD) treatment. This study also sought to determine the extent to which physical
      activity and sedentary behavior relate to depression and anxiety symptom severity
      above and beyond an established transdiagnostic risk factor for depression and
      anxiety, emotion dysregulation. A sample of 41 patients from a residential SUD
      treatment facility completed a variety of self-report measures focused on
      physical activity, sedentary behavior, emotion dysregulation, and depression and
      anxiety symptom severity. Physical activity, but not sedentary behavior, was
      found to significantly predict depression symptom severity above and beyond
      emotion dysregulation. Physical activity and sedentary behavior did not
      significantly predict anxiety symptom severity above and beyond emotion
      dysregulation. In addition to providing additional support for the relevance of
      emotion dysregulation to depression and anxiety symptom severity, results suggest
      that physical activity may be another factor to consider in evaluating risk for
      depression among patients with SUDs. Although additional research in this area is
      warranted, results also suggest the potential utility of targeting physical
      activity in reducing risk for depression among patients with SUDs.

PMID- 30294358
TI  - Empirical Evaluation of a Conceptual Model for the Perceived Value of Health
      Services.
AB  - Introduction: Perceived value and its antecedents and consequences have been
      claimed to be important in industries with higher customer involvement. The aim
      of this paper is therefore to empirically assess the conceptual model, with
      perceived service value as its central component. It also investigates how it
      affects loyalty and satisfaction, how it is influenced by its antecedents, and to
      compare with other studies investigating partial relationship between variables.
      Methods: A total of 800 patients were enrolled in the main study, and the data
      was analysed using exploratory and confirmatory factor analyses. By modelling
      linear structural equations, we assessed reliability and established the
      convergent and discriminant validity of the questionnaire in the same way as in
      the pilot study. Results: In the conceptual model for testing our hypotheses, we
      also included the relationship between patient satisfaction and loyalty. In this
      manner, the fitting of data to the model was significantly improved. After
      including the additional relationship, global fit indices had the following
      values: Chi-square=349.6 (sig.=0.00), df=143, RMSEA=0.05, NFI=0.96, CFI=0.97. All
      relationships between the constructs were statistically significant, thus
      confirming all our hypotheses. Conclusions: The major conclusion of this paper is
      that an especially higher reputation and higher perceived service quality can
      contribute to perceived service value and therefore to more satisfied patients.
      The research approach has a few limitations. In the future, the model of
      perceived service value can be extended with variables such as emotions, patient
      trust, and commitment as well.

PMID- 30294359
TI  - Outpatient Antibiotic Consumption for Urinary Infections in Croatia 2005 - 2014:
      What can be Learned from Utilization Trends.
AB  - Aim: The aim of this study was to determine quantities of antibiotics used mainly
      or exclusively for urinary tract infections in Croatia between 2005 and 2014, to
      describe utilisation trends, and general consequences of antibiotic consumption
      on antimicrobial resistance. Methods: Antibiotic utilisation data were obtained
      from annual reports of both the Croatian Drug Agency and Croatian Academy of
      Medical Sciences. Antibiotic consumption was expressed in DDD/1000
      inhabitants/day (DDD TID). Antimicrobial resistance was analysed for E. coli, E.
      faecalis, E. faecium, P. aeruginosa, Klebsiella spp., P. mirabilis. Descriptive
      statistics were used to process data and calculate trends. Results: Overall,
      utilisation of antibacterials decreased by 4.8% (from 3,35 to 3,19 DDD TID),
      while trends of individual agents varied substantially - from 87% decline for
      ceftibuten to 160% rise for levofloxacin. The consumption of quinolones increased
      by 32.3%. This was mostly due to increased ciprofloxacin consumption (144%
      raise). Sulfamethoxazole-trimethoprim declined by 57%, while nitrofurantoin
      increased by 86%. The use of fosfomycin was marginal. Antimicrobial resistance of
      E. coli increased against quinolones by 54.5%, and against nitrofurantoin by 2
      3%. Quinolone resistance of other pathogens (Klebiella spp, Proteus mirabilis),
      increased variably - between 17.2% (Klebsiella) and 90% (Proteus), while for P.
      aeruginosa remained the same at 22%. Conclusion: High rates of antimicrobial
      utilisation require prescribing restrictions and educational interventions. The
      increased use of fluoroquinolones is a potentially serious public health threat
      due to the rapid development of resistance among uropathogens. This threat can be
      avoided by greater use of nitrofurantoin and fosfomycin.

PMID- 30294360
TI  - Work-Related Stress Factors in Nurses at Slovenian Hospitals - A Cross-sectional
      Study.
AB  - Background: Surveys conducted among healthcare workers revealed that nursing
      staff often face various stressors associated with occupational activities, which
      reduce their work efficiency. The aim of the study was to establish the level of
      stress in nurses working at hospitals in Slovenia and to identify stress-related
      factors. Methods: A cross-sectional epidemiological design and a standardized
      instrument called the "Nursing stress scale" were used. The sample included 983
      nurses from 21 Slovenian hospitals. The research was conducted in 2016. Results:
      Prevalence of high level of stress was 56.5% of respondents (M (median)=75).
      Prevalence of high level of stress and stress factors may be statistically
      significant attributable to dissatisfaction at work (p<0.001), disturbing factors
      at work (p<0.001), inability to take time off in lieu after working on weekend
      (p=0.003), shorter serving (p=0.009), fixed-term work (p=0.007), and an increased
      number of workdays on Sunday (p=0.030). Conclusion: The stress rate and stress
      factors are substantially influenced by variables reflecting work organization,
      competences and skills of healthcare management to work with people. Results
      reflect the need for nursing management and policy makers to design strategies to
      ensure adequate staffing, efficient organization and an encouraging work
      environment.

PMID- 30294361
TI  - Validation of the Slovenian Version of Motor Imagery Questionnaire 3 (MIQ-3):
      Promising Tool in Modern Comprehensive Rehabilitation Practice.
AB  - Purpose: The high rate of injury incidence and its severity is estimated to cause
      approximately 9% of global mortality, while a large proportion of people
      surviving their injuries experience temporary or permanent disabilities. To
      reduce the occurrence of disability and improve general health of survivors, a
      more comprehensive rehabilitation approach is needed. Motor imagery is recognized
      as the promising cognitive strategy to counteract impaired functional capacity of
      the neuromuscular system. Thus, we aimed to provide to the Slovenian-speaking
      community a valid and reliable version of Motor Imagery Questionnaire - 3 [MIQ
      3], that consists of kinaesthetic imagery [KI] and visual [i.e., Internal Imagery
      [IMI] and external imagery [EVI]] items. Methods: We investigated both absolute
      and relative test-retest repeatability; construct validity and internal
      consistency of the KI, IMI and EMI items of the Slovenian version of MIQ-3 in 86
      healthy adult subjects. Results: Results showed high to very high average intra
      class correlation coefficient [ICC] for the visual items [ICC=0.89] and KI items
      [ICC=0.92], whilst the measure of absolute variability presented as coefficient
      of variation [CV%] ranged from 4.9% [EVI] to 6.7% [KI]. The internal consistency
      was satisfactory [Cronbach alpha=0.91 [KI] and 0.89]) for both visual items.
      Confirmatory analysis confirmed a two-factorial structure of MIQ-3. Conclusion:
      Understanding the content of the questionnaire is of utmost importance to ensure
      its effectiveness in rehabilitation practice. The Slovenian translation of the
      MIQ-3 is culturally and linguistically equivalent to the original English
      version.

PMID- 30294362
TI  - Surgical Site Infections in Slovenian Acute Care Hospitals: Surveillance Results,
      2013-2016.
AB  - Introduction: The objective was to present the results of the Slovenian National
      surgical site infections (SSIs) surveillance system from 2013 to 2016 and to
      compare them to the reference data for the European Union (EU) and European
      Economic Area (EEA) countries. Methods: Surveillance was conducted according to
      the Slovenian protocol consistent with the European Centre for Disease Prevention
      and Control protocol. Descriptive analyses were performed. Results: Data were
      collected for 1080 patients of whom 57.4% were patients with cholecystectomy
      (from three hospitals), 29.0% with caesarean sections (from four hospitals) and
      4.7%, 4.5% and 4.4% patients with hip prosthesis, knee prosthesis and colon
      surgery (each surgical category from one hospital). The pooled in-hospital SSI
      incidence density for caesarean section was 3.7 (95% CI: 1.4-8.1; inter-hospital
      range: 0.0-11.5) and for cholecystectomy 6.8 (95% CI: 3.5-11.9; inter-hospital
      range: 4.1-11.9) per 1000 post-operative patient-days. The in-hospital SSI
      incidence density for colon surgery was 24.8 (95% CI: 12.5-44.0) and for hip
      prosthesis 2.6 (95% CI: 0.1-14.2) per 1000 post-operative patient-days. No SSIs
      were reported among the 49 patients with knee prostheses. Conclusions: The
      estimated SSIs incidence rates varied between different surgical categories and
      the different participating hospitals. In some of the participating hospitals and
      for some of the surgical procedures under surveillance they were rather high in
      comparison to the reference data for hospitals from EU/EEA countries. It is
      urgent to expand standardised SSIs surveillance to all Slovenian acute care
      hospitals with surgical wards to contribute to evidence-based SSIs prevention and
      control in Slovenia.

PMID- 30294363
TI  - Correlation between the DAI and ICON Indices used for Assessment of Orthodontic
      Treatment need in Croatian Schoolchildren.
AB  - Introduction: The aims were: evaluation of the correlation between the Dental
      Aesthetic Index (DAI) and Index of Complexity, Outcome and Need (ICON); the
      assessment of orthodontic treatment need for schoolchildren in a population with
      two indices, separately for schoolchildren with mixed and permanent dentition;
      the estimation of the population share that could not receive orthodontic
      treatment because of the presence of caries and/or gingivitis. Methods: A total
      of 2652 Zagreb school children (7 - 19 years old, 52.4% of them were females)
      completed a questionnaire regarding previous orthodontic treatment and the type
      of appliance used. Their oral cavity was also inspected. The DAI and ICON indices
      were used for the assessment of malocclusion prevalence. Results: The subjects
      with mixed dentition had a greater need for orthodontic treatment, when compared
      to subjects with permanent dentition, when using the DAI index (p<0.001). When
      using the ICON index, 11.7% of subjects with mixed dentition had very severe
      malocclusion, as opposed to 5.8% of subjects with permanent dentition. The DAI
      and ICON scores correlated positively linearly (r=0.521; p<0.001). A higher
      prevalence of both gingivitis and caries was recorded more often in boys; caries
      more often in the group with the mixed dentition, and gingivitis in the group
      with permanent dentition (p<0.05). Conclusion: The DAI and ICON indices have
      moderate agreement in assessment of malocclusion severity scores. One third of
      all schoolchildren with various degrees of both ICON and DAI indices have
      gingivitis, and half of them have caries.

PMID- 30294364
TI  - Analysis of 22 Years of Surveillance for Prion Diseases in Slovenia, 1996 to
      2017.
AB  - Introduction: The objective was to present the results of surveillance of prion
      diseases in Slovenia that was established in 1996 and then to assess the
      interdisciplinary approach according to the algorithm of case management and
      reporting data to the National Register at the National Institute of Public
      Health. Methods: A descriptive study of Creutzfeldt-Jakob disease (CJD) recorded
      in the period from 1996 to 2017 was carried out. Results: A total of 123 cases of
      prion disease were notified between 1996 and 2017. Out of these, 68 were recorded
      and confirmed by autopsy as sporadic CJD with an average incidence rate of 1,5
      cases per million population per year. In one case a gene analysis showed
      mutation E200K in prion protein gene, PRNP. Two cases of the Gerstman-Straussler
      Scheinker syndrome and one clinical case of fatal insomnia with new PRNP
      mutation, N181S, were notified. Diagnostic value of protein 14-3-3 analysis in
      the liquor reached 82% sensitivity and 71% specificity. 25 cases of notified
      clinically possible/probable CJD were disproved after autopsy. In eleven notified
      possible CJD cases the autopsy had not been performed. Variant CJD has not yet
      been proven in Slovenia. Conclusion: Incidence rates were comparable with other
      European countries. Completeness of reporting and proper management of CJD cases
      according to the algorithm of reporting, management and case confirmation would
      need some improvement. A well-functioning surveillance system, including timely
      notifications, would enable an appropriate epidemiological investigation and an
      effective response to public health risks, thus the awareness of prion diseases
      should not decline.

PMID- 30294365
TI  - Selective dorsal rhizotomy in ambulant children with cerebral palsy.
AB  - Background: Selective dorsal rhizotomy (SDR) is a surgical procedure for treating
      spasticity in ambulant children with cerebral palsy (CP). However, controversies
      remain regarding indications, techniques and outcomes. Current evidence summary:
      Because SDR is an irreversible procedure, careful patient selection, a multi
      disciplinary approach in assessment and management and division of the
      appropriate proportion of dorsal rootlets are felt to be paramount for maximizing
      safety. Reliable evidence exists that SDR consistently reduces spasticity, in a
      predictable manner and to a substantial degree. However, functional improvements
      are small in the short-term with long-term benefits difficult to assess. Future
      outlook: There is a need for high-quality studies utilizing long-term functional
      outcomes and well-matched control groups. Collaborative, multicentre efforts are
      required to further define the role of SDR as part of the management paradigm in
      maximizing physical function in spastic CP.

PMID- 30294366
TI  - Trends in slipped capital femoral epiphysis: is the rate declining?
AB  - Purpose: Slipped capital femoral epiphysis (SCFE) is an adolescent hip condition
      with a high risk of complication. The purpose of this study was to evaluate
      trends in treatment using a prospectively collected paediatric nationally
      representative database. Methods: A total of 9034 patients undergoing treatment
      for idiopathic SCFE were selected by querying the Healthcare Cost and Utilization
      Project's Kids' Inpatient Database for the years 1997, 2000, 2003, 2006, 2009 and
      2012. The selected patients were separated based on operative approach and these
      cohorts were analyzed based on temporal and categorical differences in operative
      approach, patient demographics and clinical characteristics. Univariate and
      multivariate analyses were used when appropriate and the Mantel-Haenszel test for
      trend was used in temporal analysis. Results: Overall SCFE procedures have
      decreased 27.5% (p < 0.001). Closed procedures have decreased 28.5% (p < 0.001),
      while open procedures have decreased 44.8% (p < 0.001). Bilateral closed
      procedures have increased 7.2% (p < 0.001). The ratio of open to closed
      procedures decreased in patients aged nine to 12 years and increased in patients
      aged 13 to 16 years (p < 0.001). Conclusion: Here we report age stratified trends
      in treatment for idiopathic SCFE using nationally representative data and show an
      overall decrease in admissions and procedures over time. Level of Evidence: Level
      III, retrospective comparison study.

PMID- 30294367
TI  - Outcomes after slipped capital femoral epiphysis: a population-based study with
      three-year follow-up.
AB  - Purpose: To evaluate outcomes three years after treatment for slipped capital
      femoral epiphysis (SCFE): development of avascular necrosis (AVN), subsequent
      surgery, hip function and the contralateral hip. Methods: This prospective cohort
      study included a total national population of 379 children treated for SCFE
      between 2007 and 2013. A total of 449 hips treated for SCFE and 151 hips treated
      with a prophylactic fixation were identified. The Barnhoft questionnaire, a valid
      patient-reported outcome measure (PROM), was used. Results: In all, 90 hips had a
      severe slip, 61 of these were clinically unstable. AVN developed in 25 of the 449
      hips. Six of 15 hips treated with capital realignment developed AVN. A peri
      implant femur fracture occurred in three slipped hips and in two prophylactically
      pinned hips. In three of these five hips technical difficulties during surgery
      was identified. In 43 of 201 hips scheduled for regular follow-up a subsequent
      SCFE developed in the contralateral hip. Implant extraction after physeal closure
      was performed in 156 of 449 hips treated for SCFE and in 51 of 151
      prophylactically fixed hips. Children with impaired hip function could be
      identified using the Barnhoft questionnaire. Conclusion: Fixation in situ is
      justified to remain as the primary treatment of choice in SCFE. Overweight is
      more common in children with SCFE than in the average population. Prophylactic
      fixation is a safe procedure when performed using a correct technique. The number
      of patients who developed AVN after capital realignment is of concern. We
      recommend rigorous follow-up of both hips, including PROM evaluation, until
      physeal closure. Level of Evidence: II - prospective cohort study.

PMID- 30294368
TI  - Acetabular morphology in slipped capital femoral epiphysis: comparison at
      treatment onset and skeletal maturity.
AB  - Purpose: To investigate changes in acetabular morphology during the follow-up of
      slipped capital femoral epiphysis (SCFE) and search for factors associated with
      acetabular dysplasia at skeletal maturity. Methods: We evaluated 108 patients
      with unilateral SCFE (mean age at slip, 12.3 years sd 1.7) to skeletal maturity,
      with a minimum follow-up of two years (median 4.5 years; interquartile range 3.2
      to 6.2). Acetabular parameters obtained from initial and most recent radiographs
      included the lateral centre-edge angle (LCEA), Tonnis angle (TA) and acetabular
      depth-width ratio (ADR). Acetabular dysplasia was considered for LCEA < 20
      degrees  or TA > 10 degrees . Femoral parameters consisted of the most recent
      head diameter, neck-shaft angle, neck length, articulotrochanteric distance and
      alpha angle. Results: At SCFE onset, the affected hip showed a slightly lower
      LCEA (26.4 degrees  sd 6.1 degrees  versus 27.3 degrees  sd 5.7 degrees ; p =
      0.01) and ADR (330 sd 30 versus 340 sd 30; p < 0.001) compared with the
      uninvolved hip. At final follow-up, the affected hip showed lower LCEA (24.5
      degrees  sd 7.6 degrees  versus 28.8 degrees sd 6.6 degrees ; p < 0.001) and ADR
      (330 sd 40 versus 350 sd 40; p < 0.001), and TA was larger (5.5 degrees  sd 5.4
      degrees  versus 2.3 degrees  sd 4.2 degrees ; p < 0.001) compared with the
      uninvolved hip. Acetabular dysplasia was observed in 27 (25%) of 108 hips with
      SCFE. Femoral head overgrowth, age at slip and SCFE severity were independent
      factors associated with acetabular dysplasia (p < 0.05). Conclusion: Acetabular
      coverage and depth are not increased in SCFE, and the acetabular coverage tends
      to decrease up to skeletal maturity. A potential disturbance in the acetabular
      growth and remodelling exists mainly for young children with severe SCFE, and a
      potential for acetabular insufficiency may be observed at the diagnosis and
      follow-up of SCFE. Level of Evidence: Prognostic Level IV.

PMID- 30294369
TI  - MRI in idiopathic, stable, slipped capital femoral epiphysis: evaluation of
      contralateral pre-slip.
AB  - Purpose: Early diagnosis and treatment of slipped capital femoral epiphysis
      (SCFE) is important to prevent slip progression and avoid complications. We
      sought to determine if MRI findings in patients with unilateral SCFE could
      indicate 'pre-slip' or predict future SCFE in the contralateral hip. Methods: A
      prospective study evaluated patients with unilateral SCFE over a two-year period.
      MRI of the asymptomatic hip was performed within the perioperative period.
      Patients were followed with radiographs until a contralateral slip occurred or
      until physeal closure. Demographics, clinical stability, severity, posterior
      slope angle (PSA), modified Oxford Bone Score (mOBS) and patency of the
      triradiate cartilage were recorded and statistical analysis performed. Results:
      In all, 33 of 54 patients with unilateral SCFE were enrolled into the study. In
      all, 29 (87.8%) had complete follow-up. Five of the enrolled patients (15.2%)
      developed a sequential slip requiring in situ pinning. Six of 33 (18.2%) patients
      had positive MRI findings: four of which proceeded to sequential SCFE and two
      which did not. One sequential slip had a negative MRI. PSA predicted 1/11
      sequential slips (sensitivity 9.09%, specificity 81.4%, positive predictive value
      (PPV) 11.1%, negative predictive value (NPV) 77.8%) and mOBS predicted 5/11
      sequential slips (sensitivity 45.5%, specificity 93%, PPV 62.5%, NPV 87%). An
      open triradiate cartilage was present in 8/11 patients with sequential slips
      (sensitivity 72.7%, specificity 81.4%, PPV 50%, NPV 92.1%). Conclusion: MRI
      findings consistent with 'pre-slip' were present in 66.7% of patients who
      developed a sequential SCFE. Further study on the utility/sensitivity of MRI in
      predicting sequential SCFE is warranted. Level of Evidence: II, diagnostic.

PMID- 30294370
TI  - San Diego pelvic osteotomy in patients with closed triradiate cartilage.
AB  - Purpose: A San Diego pelvic osteotomy is frequently used as part of the surgical
      treatment of neuromuscular patients with hip displacement. This short-term follow
      up study assesses the effectiveness of this osteotomy in patients with closed
      triradiate cartilage compared with open triradiates. Methods: Retrospective
      review of 43 patients (44 hips) with neuromuscular hip disease who underwent a
      San Diego pelvic osteotomy to correct hip displacement. In all 24 hips had open
      triradiate cartilage at the time of surgery and 20 hips were closed. Centre edge
      angle (CEA), acetabular angle (AA) and Reimer's index (RI) were recorded from
      preoperative, postoperative and the latest follow-up radiographs and statistical
      analysis was performed. Results: CEA improved by 39 degrees  (7 degrees  to 69
      degrees ) in the open group and 30 degrees  (9 degrees  to 80 degrees ) in the
      closed group from preoperative radiographs to postoperative, with no significant
      difference in improvement between groups (p = 0.084). There was no significant
      difference in AA between the open (improved by 11 degrees  (3 degrees  to 23
      degrees )) and closed (improved by 10 degrees  (4 degrees  to 21 degrees ))
      groups (p = 0.65). RI improved from 61% to 11% in the open group and 51% to 12%
      in the closed group. There was no statistically significant difference between
      groups in RI at preoperative, immediate postoperative and final follow-up
      radiographs. At latest follow-up, CEA, AA and RI all remained relatively stable
      in both groups. Conclusions: San Diego pelvic osteotomy is equally effective in
      improving radiographic parameters in neuromuscular patients with both open and
      closed triradiate cartilage. This study challenges the notion that closed
      triradiate cartilage is a contraindication to a San Diego pelvic osteotomy. Level
      of Evidence: III.

PMID- 30294371
TI  - MRI and sonography in Legg-Calve-Perthes disease: clinical relevance of
      containment and influence on treatment.
AB  - Purpose: The containment orientated treatment of Legg-Calve-Perthes disease
      (LCPD) affected hip joints is broadly accepted in the literature. The
      prerequisite is early recognition of loss of containment. An often-used
      quantitative MRI containment parameter is the cartilaginous acetabulum-head-index
      (CAHI). Based on ultrasound (US), we analyzed the newly created 'femoral head
      extrusion angle' (HA) as a containment parameter in comparison with the CAHI in
      severe LCPD. Methods: In a prospective study with 40 children (mean age 5.8 years
      sd 2.3) with unilateral LCPD classified as Catterall group III/IV, we measured
      the CAHI versus HA to assess the containment of the femoral head. HA in US was
      determined by the tangent from the bony acetabular rim to the cartilaginous
      cranio-lateral femoral head. Results: The HA was significantly higher in LCPD
      affected hip joints (25 degrees  sd 7 degrees ) than in healthy ones (13 degrees 
      sd 5 degrees ; p < 0.001). Correlation analysis of all hip joints revealed a
      significant correlation between HA and CAHI (r = -0.69; p < 0.001). Hip joints
      with a low CAHI indicating loss of containment showed a higher HA in sonography.
      Conclusion: The results of our study suggest that the HA in US is a reliable
      containment parameter in severe LCPD with a HA > 22 degrees  defining a
      pathologic value. In comparison with the CAHI, HA measurement in ultrasound is
      easier than the assessment of various parameters to calculate an index. Frequent
      sonographical follow-up assessment in critical joints is an alternative if MRI is
      not available, helping to detect an impending loss of containment early enough.
      Level of Evidence: Level II.

PMID- 30294372
TI  - Early morbidity associated with fasciotomies for acute compartment syndrome in
      children.
AB  - Purpose: Acute compartment syndrome (ACS) requires urgent fasciotomy to
      decompress the relevant muscle compartment/s prior to onset of irreversible
      myonecrosis and nerve injury. A fasciotomy is not a benign procedure. This study
      aims to describe and quantify early morbidity directly associated with
      fasciotomies for ACS in children. Methods: Clinical charts of 104 children who
      underwent 112 fasciotomies over a 13-year period at a tertiary children's
      hospital were reviewed. The following were analyzed: ACS aetiology, fasciotomy
      site, number of subsequent procedures, method of wound closure, short-term
      complications and length of hospital stay. Results: Short-term complications
      included wound infections (6.7%) and the need for blood transfusion (7.7%).
      Median number of additional operations for wound closure was two (0 to 10) and
      median inpatient stay was 12 days (3 to 63; SD 11.7). After three unsuccessful
      attempts at primary closure, likelihood of needing skin grafting for coverage
      exceeded 80%. Analyses showed that fasciotomy-wound infections were associated
      with higher risk for four or more closure procedures. Number of procedures
      required for wound closure correlated with longer inpatient stay as did ACS
      associated with non-orthopaedic causes. Conclusion: Fasciotomy is associated with
      significant early morbidity, the need for multiple closure operations, and
      prolonged hospital stay. The decision for fasciotomy needs careful consideration
      to avoid unnecessary fasciotomies, without increasing the risk of permanent
      injury from missed or delayed diagnosis. Skin grafting should be considered after
      three unsuccessful closure attempts. Less invasive tests or continuous monitoring
      (for high-risk patients) for compartment syndrome may help reduce unnecessary
      fasciotomies. Level of Evidence: Level IV, Case series.

PMID- 30294373
TI  - Submuscular plates versus flexible nails in preadolescent diaphyseal femur
      fractures.
AB  - Purpose: To compare patient characteristics, operative time, estimated blood loss
      (EBL), postoperative length of hospital stay (LOS) and complications after
      insertion and removal of submuscular plates (SMPs) versus flexible nails (FNs)
      for paediatric diaphyseal femur fractures. Methods: We reviewed records of 58
      children (mean age, 7.7 years SD 2.0) with diaphyseal femur fractures who
      underwent treatment with SMPs (n = 30) or FNs (n = 28) from 2005 to 2017 (mean
      follow-up, 22 months SD 28). Patients with pathological fractures or
      musculoskeletal comorbidities were excluded. Alpha = 0.05. Results: Insertion of
      FNs was associated with shorter operative time (beta = -24 mins) and less EBL
      (beta = -38 mL) (both, p < 0.001) compared with insertion of SMPs, after
      adjusting for fracture type and time from beginning of study period. Removal of
      FNs was also associated with shorter operative time (beta = -15 min) compared
      with removal of SMPs (p < 0.001). EBL during removal was similar between groups
      (p = 0.080). The FN group had a shorter LOS after insertion (beta = -0.2 d)
      compared with the SMP group (p = 0.032). Four patients treated with SMPs and
      three treated with FNs developed surgical site infections. Two patients treated
      with SMPs and seven treated with FNs experienced implant irritation that resolved
      with removal. No other complications occurred. Conclusion: Compared with SMPs,
      FNs were associated with shorter operative time (for insertion and removal), less
      EBL (for insertion) and shorter post-insertion LOS in patients with diaphyseal
      femur fractures. Level of Evidence: III.

PMID- 30294374
TI  - No incidence of glenohumeral joint dislocation in a review of 220 paediatric
      proximal humerus fractures.
AB  - Purpose: Proximal humerus fractures in adults are approached with a high
      suspicion for potential associated glenohumeral dislocation. Axillary views of
      the shoulder can be painful and possibly even lead to dynamic angulation of the
      proximal humerus fracture. The incidence of associated glenohumeral dislocation
      in the paediatric population is unclear and it would be useful to determine
      whether children with proximal humerus fracture require specific axillary view
      imaging to rule out dislocation. Methods: We retrospectively reviewed 220
      proximal humerus fractures in 218 total children. Imaging and follow-up clinic
      notes were reviewed for potential glenohumeral dislocation. Results: Average
      patient age was 9.8 years SD 3.8 with 55% of the patients male and a wide variety
      of mechanisms of injury. None of the 220 fractures evaluated showed radiographic
      evidence of a shoulder dislocation, and all 218 children had a follow-up
      appointment at least 21 days after the injury without any clinical concern of a
      missed shoulder dislocation. Conclusion: No paediatric patients presenting with
      proximal humerus fractures had a corresponding glenohumeral joint dislocation in
      our relatively large series. We recommend obtaining this additional imaging only
      in cases with higher energy mechanisms, if there is suspicion of subluxation or
      dislocation on anteroposterior and scapular-Y views or if there is clinical
      concern. Level of Evidence: Level III Diagnostic.

PMID- 30294375
TI  - Olecranon fractures in children and adolescents: outcomes based on fracture
      fixation.
AB  - Purpose: Open reduction and internal fixation with a tension band construct is
      the standard treatment for displaced transverse intra-articular olecranon
      fractures. The purpose of this study is to describe the outcomes of tension band
      fixation of olecranon fractures in children, specifically assessing the need for
      revision fixation and hardware removal. Methods: Patients less than 18 years of
      age diagnosed with a displaced transverse intra-articular olecranon fracture and
      treated with tension band fixation between 2008 and 2017 were retrospectively
      enrolled. Operative treatment was with tension band wire (TBW) or tension band
      suture (TBS) constructs. Results: A total of 46 patients, 36 male and ten female
      with a mean age of 12.3 years (6 to 17), were included. Surgical fixation was
      with TBW in 17 patients and TBS in 29 patients. Revision fixation due to failure
      and fracture displacement was required in 6% of the TBW group and 14% of the TBS
      group (p = 0.19). The patients who required revision fixation in the TBS group
      were older (14.7 years versus 11.6 years, p = 0.05) and heavier (70.5 kg versus
      48.5 kg, p = 0.05) than those in the same group who did not require revision
      fixation. Conclusion: Paediatric olecranon fractures treated with TBW or TBS
      fixation unite in the majority of patients with similar need for hardware removal
      due to prominence and/or pain between fixation techniques. In a select group of
      older patients weighing greater than 50 kg, TBS constructs demonstrate increased
      failure rates, requiring revision fixation, and should be avoided in this
      population group. Level of Evidence: IV.

PMID- 30294376
TI  - Is less more? Assessing the utility of early clinical and radiographic follow-up
      for operative supracondylar humerus fractures.
AB  - Purpose: Postoperative protocols following surgical management of supracondylar
      humerus fractures (SCFs) are often based upon surgeon preference rather than
      clinical merit. The purpose of this study is to determine the utility of early
      clinical and radiographic follow-up. Methods: A retrospective review of patients
      who underwent closed reduction and percutaneous pinning (CRPP) for SCF between
      2009 and 2015 was performed using a database of prospectively-collected
      consecutive patient data. Previously undiagnosed neuropathies documented at the
      first postoperative visit were identified. Unscheduled visits and postoperative
      complications were compared between patients who were seen at one week and those
      with delayed first clinic visits. Results: Of 873 patients, 823 (94.3%) were seen
      within ten days of surgery (early follow-up) and 50 (5.7%) had a delayed first
      clinic appointment. Among patients seen for early follow-up, 12 (1.5%) had a
      previously undocumented neuropathy diagnosed but only eight (1%) had an
      alteration of management secondary to clinical findings. Greater than 90% of
      patients seen for early follow-up had radiographs performed, but only one had an
      alteration in management due to radiographic findings. Patients seen for early
      follow-up had the same rate of unscheduled visits (2.9% versus 4%, p = 0.66) and
      postoperative complications (1.6% versus 0%, p > 0.99) as those with delayed
      first appointments. Radiographic parameters were comparable at final follow-up
      (Baumann's angle 74.5 degrees  versus 73.7 degrees , p = 0.40; lateral humeral
      condylar angle 40.2 degrees  versus 41.2 degrees , p = 0.53). Conclusion: The
      early follow-up visit after CRPP of SCF rarely leads to alterations in care and
      does not reduce unscheduled visits or late complications. Level of Evidence:
      Level IV.

PMID- 30294377
TI  - A comparison of screw versus drill and curettage epiphysiodesis to correct leg
      length discrepancy.
AB  - Purpose: To compare two common surgical techniques of epiphysiodesis:
      drill/curettage epiphysiodesis (PDED) versus cross screw epiphysiodesis (PETS).
      The hypothesis is that the two techniques have similar efficacy but demonstrate
      differences in length of hospital stay (LOS), time to return to activity and
      complication rates. Methods: A retrospective review of growing children and
      adolescents less than 18 years old who required an epiphysiodesis with leg-length
      discrepancy (LLD) of 2 cm to 6 cm with minimum two years of follow-up was
      conducted. Characteristics including age at surgery, gender, epiphysiodesis
      location, side, operative time, LOS and hardware removal were compared across
      treatment groups. LLD, expected growth remaining (EGR) and bone age were
      determined preoperatively and at most-recent visit. The correction ratio (change
      in EGR) was calculated along with a 95% confidence interval (CI) to assess if
      correction in leg length was achieved. Results: A total of 115 patients underwent
      epiphysiodesis in the femur (53%), tibia (24%) or a combination (24%). The cohort
      was 47% male, with a mean age of 12.6 years (7.7 to 17.7) at surgery. Median
      follow-up was 3.7 years (2.0 to 12.7). In all, 23 patients underwent PETS and 92
      patients had PDED. Both treatment groups achieved expected LLD correction. There
      was no significant difference in median operative time, complication rates or
      LOS. PETS patients returned to activity at a mean 1.4 months (interquartile range
      (IQR) 0.7 to 2.1) while PDED patients returned at a mean 2.4 months (IQR 1.7 to
      3) (p < 0.001). Conclusion: Effectiveness in achieving expected correction, LOS
      and operative time are similar between screw and drill/curettage epiphysiodesis.
      Patients undergoing PETS demonstrated a faster return to baseline activity than
      patients with PDED. Level of Evidence: III.

PMID- 30294378
TI  - A new technique for correction of leg length discrepancies in combination with
      complex axis deformities of the lower limb using a lengthening nail and a locking
      plate.
AB  - Purpose: Intramedullary lengthening nails are an accepted alternative to external
      fixators but are limited by anatomical preconditions. Therefore, to date the use
      of external fixators is sometimes inevitable. We report on a new technique for
      correction of combined limb length discrepancies and complex axis deformities
      using solely internal devices - a lengthening nail and a locking plate. Methods:
      Between October 2008 and November 2011 five patients (two femora, three tibias)
      with a mean leg length discrepancy of 36 mm (25 to 50) and a complex angular
      deformity were treated with a fully implantable motorized lengthening nail
      (Fitbone) and a locking plate. All patients were evaluated with regards to the
      pre- and postoperative leg length as well as axis alignment, functional outcome,
      lengthening indices and complications. Results: A successful leg length
      equalization was achieved in all cases and physiological joint orientation angles
      in all but one case. The mean distraction index was 1.2 mm/day, the maturation
      index 24 days/cm and the consolidation index 35 days/cm. The functional outcome
      was very encouraging in all cases with bilateral free range of movement. In
      total, two complications were observed, one nonunion and one loss of leg length
      after an early locking bolt removal in a peripheral hospital. Conclusion: The
      combination of a fully implantable motorized lengthening nail and a locking plate
      is a valuable alternative option for treating selected cases with limb length
      discrepancies in combination with a complex deformity of the lower leg. However,
      the reported technique puts high demands on the preoperative planning, operative
      technique as well as surgeon's skills. Level of evidence: IV (retrospective
      series).

PMID- 30294379
TI  - Range of motion in the talo-navicular and the calcaneo-cuboid joints evaluated by
      ultrasound during clubfoot treatment with normal references up to the age of four
      years.
AB  - Purpose: Previous ultrasound studies of clubfeet have mainly focused on the first
      year of life. The purpose of this study was to improve the evaluation of the talo
      navicular and calcaneo-cuboid joints by adding new variables, evaluating the
      repeatability of ultrasound measurements for normal feet and clubfeet and
      establishing values for normal feet up to four years of age. Methods: A control
      group of 105 children divided into ten age groups, and 71 clubfeet in 46 children
      were examined. Four new variables were introduced: medial malleolus-Talar head
      Navicular distance, medial tangent of the talus to the medial border of the
      navicular distance, the angle between the longitudinal axis of the talus and a
      line from the centre of the talar head to the medial corner of the navicular, the
      angle between the lateral borders of the calcaneus and the cuboid. The mobility
      in the talo-navicular and the calcaneo-cuboid joints was assessed by comparing
      measurements with the foot in adduction and abduction. Results: The variables
      could be assessed with fair to very good intra- and inter-observer repeatability
      (intraclass correlation coefficient > 0.8 and >= 0.6, respectively), with a few
      exceptions. There was less movement in talo-navicular and calcaneo-cuboid joints
      in clubfeet than in controls. Conclusion: Morphology of normal feet and clubfeet,
      as well as mobility in the talo-navicular and calcaneo-cuboid joints, can be
      assessed by ultrasound with a fair to very good reliability from birth to the age
      of four years. Level of Evidence: III.

PMID- 30294380
TI  - Stomaching the pain of spinal fusion: gastrointestinal discomfort is as severe as
      back pain in 50% of adolescent idiopathic scoliosis patients following posterior
      spinal fusion.
AB  - Purpose: There have been no prospective studies investigating gastrointestinal
      (GI) symptoms of patients with adolescent idiopathic scoliosis (AIS) following
      posterior spinal fusion (PSF). The purpose of this study was to evaluate the
      incidence and severity of self-reported GI symptoms following PSF. Methods: In
      all, 40 AIS patients undergoing PSF were prospectively enrolled between March
      2015 and October 2016. Patients completed a survey on each postoperative,
      inpatient day regarding nausea, emesis, constipation, abdominal pain and back
      pain, rating their pain on a scale of 1 to 10. Results: Abdominal pain (50%),
      emesis (63%), nausea (65%) and constipation (68%) were experienced by the
      majority of patients. Of those reporting back pain, the mean pain level during
      the postoperative period was 5.1 (0.2 to 9.6). Of those reporting abdominal pain,
      the mean pain level during the postoperative period was 5.5 (1.4 to 8.6), which
      was not different than the severity of their back-pain levels (mean = 6.0, p =
      0.31). Conclusions: Gastrointestinal issues in AIS patients following PSF are
      common. Abdominal pain was as severe as the back pain for half of the patients.
      Level of Evidence: II.

PMID- 30294381
TI  - What influences contracture formation in lower motor neuron disorders, severity
      of denervation or residual muscle function? An analysis of the elbow contracture
      in 100 children with unilateral Brachial Plexus Birth Injury.
AB  - Purpose: As in other neuromuscular disorders, both denervation and muscle
      paresis/imbalance are implicated as aetiological factors for contractures in
      children with a Brachial Plexus Birth Injury (BPBI). Although both factors are
      related, it is unclear which factor is dominant. The aim of this study is to
      assess whether contracture formation in children is predominantly related to
      denervation or to residual muscle function/imbalance. This might be relevant for
      understanding contracture formation in other neuromuscular disorders. Methods: A
      total of 100 children (61 boys; mean age 10.4 years, 4 to 18) with unilateral
      BPBI were included in this cross-sectional study. Severity of the denervation was
      classified according to Narakas. Muscle function of flexors and extensors of both
      elbows was measured (in Newtons) using a hand-held dynamometer and flexion
      contractures were measured with a goniometer. The relation between denervation,
      muscle function/muscle balance and flexion contracture was assessed using
      univariate and multivariate analysis. Results: Of the children, 57 were Narakas
      class I, 13 class II and 30 class III. Mean flexion contracture was 25 degrees 
      (90 degrees  to -5 degrees ). At the affected side the forearm flexion force was
      47% and extension force was 67% of the force of the unaffected side. Contractures
      were more severe in children with higher Narakas classifications (p = 0.001),
      after neurosurgery (Mann-Whitney U test, p = 0.009) and were related to age
      (Spearman's Rho = -0.3, p = 0.008) and to paresis of the extensors (Rho = 0.4, p
      = 0.000). Flexor paresis as a percentage of unaffected side (Rho = 0.06, p = 0.6)
      and muscle balance had no influence. Conclusion: In BPBI, elbow contractures are
      related to the severity of the neurological lesion, not to residual muscle
      function. Level of evidence: Level II - prognostic study.

PMID- 30294382
TI  - Intraoperative 2D C-arm and 3D O-arm in children: a comparative phantom study.
AB  - Purpose: Exposure to ionizing radiation is a concern for children during
      intraoperative imaging. We aimed to assess the radiation exposure to the
      paediatric patient with 2D and 3D imaging. Methods: To evaluate the radiation
      exposure, patient absorbed doses to the organs were measured in an
      anthropomorphic phantom representing a five-year-old child, using
      thermoluminescent dosimeters. For comparative purposes, organ doses were measured
      using a C-arm for one minute of fluoroscopy and one acquisition with an O-arm.
      The cone-beam was centred on the pelvis. Direct and scattered irradiations were
      measured and compared (Student's t-test). Skin entrance dose rates were also
      evaluated. Results: All radiation doses were expressed in uGy. Direct radiation
      doses of pelvic organs were between 631.22 and 1691.87 for the O-arm and between
      214.08 and 737.51 for the C-arm, and were not significant (p = 0.07). Close
      scattered radiation on abdominal organs were between 25.11 and 114.85 for the O
      arm and between 8.03 and 55.34 for the C-arm, and were not significant (p =
      0.07). Far scattered radiation doses on thorax, neck and head varied from 0.86 to
      6.42 for the O-arm and from 0.04 to 3.08 for the C-arm, and were significant (p =
      0.02). The dose rate at the skin entrance was 328.58 uGy.s-1 for the O-arm and
      1.90 with the C-arm. Conclusion: During imaging of the pelvis, absorbed doses for
      a 3D O-arm acquisition were higher than with one minute fluoroscopy with the C
      arm. Further clinical studies comparing effective doses are needed to assess
      ionizing risks of the intraoperative imaging systems in children.

PMID- 30294383
TI  - Population and forest dynamics during the Central European Eneolithic (4500-2000
      BC).
AB  - The population boom-and-bust during the European Neolithic (7000-2000 BC) has
      been the subject of lively discussion for the past decade. Most of the research
      on this topic was carried out with help of summed radiocarbon probability
      distributions. We aim to reconstruct population dynamics within the catchment of
      a medium sized lake on the basis of information on the presence of all known past
      human activities. We calculated a human activity model based on Monte Carlo
      simulations. The model showed the lowest level of human activity between 4000 and
      3000 BC. For a better understanding of long-term socio-environmental dynamics, we
      also used the results of a pollen-based quantitative vegetation model, as well as
      a local macrophysical climate model. The beginning of the decline of
      archaeologically visible human activities corresponds with climatic changes and
      an increase in secondary forest taxa probably indicating more extensive land-use.
      In addition, important social and technological innovations, such as the
      introduction of the ard, wheel, animal traction and metallurgy, as well as
      changes in social hierarchy characterizing the same period.

PMID- 30294384
TI  - Efficient two-stage designs and proper inference for animal studies.
AB  - Cost-effective yet efficient designs are critical to the success of animal
      studies. We propose a two-stage design for cost-effectiveness animal studies with
      continuous outcomes. Given the data from the two-stage design, we derive the
      exact distribution of the test statistic under null hypothesis to appropriately
      adjust for the design's adaptiveness. We further generalize the design and
      inferential procedure to the K-sample case with multiple comparison adjustment.
      We conduct simulation studies to evaluate the small sample behavior of the
      proposed design and test procedure. The results indicate that the proposed test
      procedure controls the type I error rate for the one-sample design and the family
      wise error rate for K-sample design very well; whereas the naive approach that
      ignores the design's adaptiveness due to the interim look severely inflates the
      type I error rate or family-wise error rate. Compared with the standard one-stage
      design, the proposed design generally requires a smaller sample size.

PMID- 30294385
TI  - Mindfulness-Based Interventions for Young Offenders: a Scoping Review.
AB  - Youth offending is a problem worldwide. Young people in the criminal justice
      system have frequently experienced adverse childhood circumstances, mental health
      problems, difficulties regulating emotions and poor quality of life. Mindfulness
      based interventions can help people manage problems resulting from these
      experiences, but their usefulness for youth offending populations is not clear.
      This review evaluated existing evidence for mindfulness-based interventions among
      such populations. To be included, each study used an intervention with at least
      one of the three core components of mindfulness-based stress reduction (breath
      awareness, body awareness, mindful movement) that was delivered to young people
      in prison or community rehabilitation programs. No restrictions were placed on
      methods used. Thirteen studies were included: three randomized controlled trials,
      one controlled trial, three pre-post study designs, three mixed-methods
      approaches and three qualitative studies. Pooled numbers (n = 842) comprised 99%
      males aged between 14 and 23. Interventions varied so it was not possible to
      identify an optimal approach in terms of content, dose or intensity. Studies
      found some improvement in various measures of mental health, self-regulation,
      problematic behaviour, substance use, quality of life and criminal propensity. In
      those studies measuring mindfulness, changes did not reach statistical
      significance. Qualitative studies reported participants feeling less stressed,
      better able to concentrate, manage emotions and behaviour, improved social skills
      and that the interventions were acceptable. Generally low study quality limits
      the generalizability of these findings. Greater clarity on intervention
      components and robust mixed-methods evaluation would improve clarity of reporting
      and better guide future youth offending prevention programs.

PMID- 30294386
TI  - Intervention Integrity in Mindfulness-Based Research.
AB  - Assessing program or intervention fidelity/integrity is an important
      methodological consideration in clinical and educational research. These critical
      variables influence the degree to which outcomes can be attributed to the program
      and the success of the transition from research to practice and back again.
      Research in the Mindfulness-Based Program (MBP) field has been expanding rapidly
      over the last 20 years, but little attention has been given to how to assess
      intervention integrity within research and practice settings. The proliferation
      of different program forms, inconsistency in adhering to published curriculum
      guides, and variability of training levels and competency of trial teachers all
      pose grave risks to the sustainable development of the science of MBPs going
      forward. Three tools for assessing intervention integrity in the MBP field have
      been developed and researched to assess adherence and/or teaching competence: the
      Mindfulness-Based Cognitive Therapy-Adherence Scale (MBCT-AS), the Mindfulness
      Based Relapse Prevention-Adherence and Competence Scale (MBRP-AC), and the
      Mindfulness-Based Interventions: Teaching Assessment Criteria (MBI:TAC). Further
      research is needed on these tools to better define their inter-rater reliability
      and their ability to measure elements of teaching competence that are important
      for participant outcomes. Research going forward needs to include systematic and
      consistent methods for demonstrating and verifying that the MBP was delivered as
      intended, both to ensure the rigor of individual studies and to enable different
      studies of the same MBP to be fairly and validly compared with each other. The
      critical variable of the teaching also needs direct investigation in future
      research. We recommend the use of the "Template for Intervention Description and
      Replication" (TIDieR) guidelines for addressing and reporting on intervention
      integrity during the various phases of the conduct of research and provide
      specific suggestions about how to implement these guidelines when reporting
      studies of mindfulness-based programs.

PMID- 30294387
TI  - Towards an Objective Measure of Mindfulness: Replicating and Extending the
      Features of the Breath-Counting Task.
AB  - Despite calls for objective measures of mindfulness to be adopted in the field,
      such practices have not yet become established. Recently, a breath-counting task
      (BCT) was proposed as a reliable and valid candidate for such an instrument. In
      this study, we show that the psychometric properties of the BCT are reproducible
      in a sample of 127 Asian undergraduates. Specifically, accuracy on the BCT was
      associated with everyday lapses and sustained attention, and weakly associated
      with subjectively measured mindfulness. BCT metrics also showed good test-retest
      reliability. Extending the use of the paradigm, we further found that two
      different types of task errors-miscounts and resets-were correlated with
      different aspects of cognition. Miscounts, or errors made without awareness, were
      associated with attentional lapses, whereas resets, or self-caught errors, were
      associated with mind-wandering. The BCT may be a suitable candidate for the
      standardized measurement of mindfulness that could be used in addition to
      mindfulness questionnaires.

PMID- 30294388
TI  - A Close Examination of the Relationship Between Self-Compassion and Depressive
      Symptoms.
AB  - Self-compassion has shown to be beneficial for individuals' wellbeing; in
      particular, it has been associated with lower levels of depressive symptoms. The
      purpose of this study was to further explore the association between self
      compassion, as measured by the Self-Compassion Scale (SCS), and depressive
      symptoms, in a large representative sample of community adults (n = 734, Mean age
      = 55.7, SD = 15.2). We examined the association of depressive symptoms with the
      SCS total score, the SCS six subscales (i.e., self-kindness, common humanity,
      mindfulness, self-judgment, isolation, and over-identification), and the SCS
      positive and negative items (referred to as self-compassion and self-coldness,
      respectively). In addition, we explored the predictive ability of self
      compassion, self-coldness, and the SCS six subscales on depressive symptoms both
      cross-sectionally and over a 1-year period of time. Finally, we sought to test
      the moderating role of self-compassion on the association between self-coldness
      and depressive symptoms. Results showed that the SCS negative items and subscales
      were more strongly related to depressive symptoms than the SCS positive items and
      subscales. Accordingly, self-coldness was a stronger predictor of depressive
      symptoms, cross-sectionally and over a 1-year timeframe, when compared with self
      compassion. Particularly, the feeling of being isolated was shown to be strongly
      associated with depressive symptoms. We did not find substantial evidence for a
      moderating role of self-compassion on the association between self-coldness and
      depressive symptoms. Future research needs to determine the added value of
      assessing self-coldness and whether or not it is an essential part of self
      compassion.

PMID- 30294389
TI  - On the Association Between Mindfulness and Romantic Relationship Satisfaction:
      the Role of Partner Acceptance.
AB  - In three studies, it was investigated whether trait mindfulness is positively
      associated with partner acceptance, defined as the ability and willingness to
      accept the partner's imperfections, and whether partner acceptance explains the
      association between trait mindfulness and relationship satisfaction. Trait
      mindfulness, partner acceptance and relationship satisfaction were assessed in
      two MTurk samples (n 1 = 190; n 2 = 140) and a sample of participants of a
      mindfulness-based stress reduction course (n 3 = 118) and their partners (53
      complete couples), using self-report measures. In all three samples, trait
      mindfulness was related to partner acceptance and in two out of three studies
      trait mindfulness was directly positively related to relationship satisfaction.
      Also, the results provided initial support for the mediating role of partner
      acceptance in the association between mindfulness and relationship satisfaction.
      Dyadic data further suggested that the benefits of mindfulness and partner
      acceptance on relationship satisfaction extend from the individual to the partner
      through increased partner acceptance. Together, the results provide initial
      support for the hypothesis that partner acceptance may be an important mechanism
      through which mindfulness promotes relationship satisfaction in both partners of
      a romantic couple.

PMID- 30294390
TI  - Improvements in Stress, Affect, and Irritability Following Brief Use of a
      Mindfulness-based Smartphone App: A Randomized Controlled Trial.
AB  - Mindfulness training, which involves observing thoughts and feelings without
      judgment or reaction, has been shown to improve aspects of psychosocial well
      being when delivered via in-person training programs such as mindfulness-based
      stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT). Less is
      known about the efficacy of digital training mediums, such as smartphone apps,
      which are rapidly rising in popularity. In this study, novice meditators were
      randomly allocated to an introductory mindfulness meditation program or to a
      psychoeducational audiobook control featuring an introduction to the concepts of
      mindfulness and meditation. The interventions were delivered via the same
      mindfulness app, were matched across a range of criteria, and were presented to
      participants as well-being programs. Affect, irritability, and two distinct
      components of stress were measured immediately before and after each intervention
      in a cohort of healthy adults. While both interventions were effective at
      reducing stress associated with personal vulnerability, only the mindfulness
      intervention had a significant positive impact on irritability, affect, and
      stress resulting from external pressure (between group Cohen's d = 0.44, 0.47,
      0.45, respectively). These results suggest that brief mindfulness training has a
      beneficial impact on several aspects of psychosocial well-being, and that
      smartphone apps are an effective delivery medium for mindfulness training.

PMID- 30294392
TI  - Accessing the elite figured world of science.
AB  - This review explores Jackson and Seiler's "I am smart enough to study post
      secondary science: A critical discourse analysis of latecomers' identity
      construction in an online forum" by considering the analytic framework for
      figured worlds guiding this study. We consider the specific affordances of
      cultural production theory for examining how sociohistorical and cultural
      discourses of science as elite impact individuals at every level of education. We
      then extend this discussion by exploring how an informal learning space at a
      prestigious science museum was designed to explicitly tackle cultural discourses
      of science as elite that act as barriers to identification with science.

PMID- 30294391
TI  - High-Risk Acute Promyelocytic Leukemia with Unusual T/Myeloid Immunophenotype
      Successfully Treated with ATRA and Arsenic Trioxide-Based Regimen.
AB  - We describe two patients with acute promyelocytic leukemia (APL) with an unusual
      immunophenotype with co-expression of myeloperoxidase (MPO) with cytoplasmic CD3
      (cCD3) representing myeloid and T-lineage differentiation. Both harbored FLT3-ITD
      mutations. One additionally had a deletion in the PML gene affecting the primer
      binding site, thus limiting measurable residual disease (MRD) analysis during
      follow-up. Both patients achieved durable remission with all-trans retinoic acid
      (ATRA) and arsenic trioxide (ATO)-based therapy, thus mitigating the need for
      repetitive conventional chemotherapy cycles and allogeneic stem cell
      transplantation. Our report highlights the complexity and challenge of diagnosis
      and management of APL due to the variant immunophenotype and genetics, and
      underscores the importance of synthesizing information from all testing
      modalities. The association of the unusual immunophenotype and FLT3-ITD mutation
      illustrates the plasticity of the hematopoietic stem cell and the pathobiology of
      leukemia with mixed lineage or lineage infidelity.

PMID- 30294393
TI  - Outcomes of Wavefront-Optimized Laser-Assisted In-Situ Keratomileusis and
      Photorefractive Keratectomy for correction of Myopia and Myopic Astigmatism over
      One Year Follow-Up.
AB  - Background: Laser corneal refractive surgery suits, technology and nomograms are
      improving with time. This may improve the refractive and visual outcomes of the
      patients. Objectives: To evaluate the safety, efficacy, stability, and
      predictability of wavefront-optimized photorefractive keratectomy and Laser
      assisted in-situ keratomileusis in patients with myopia and myopic astigmatism
      over 1-year using WaveLight(r) EX500 Excimer Laser machine. Methods: In this
      prospective cohort study, refractive and visual outcomes in 596 eyes (365
      patients), either having myopia or myopic astigmatism were assessed. Patients
      were divided into Two groups: 1) Patients who underwent PRK (53 eyes have myopia
      and 217 eyes have myopic astigmatism), 2) Patients who underwent LASIK (53 eyes
      have myopia and 273 eyes have myopic astigmatism). Results: At 12 months
      postoperatively 94.3% of the myopic patients reached their preoperative best
      corrected distance visual acuity at the final one year follow up visit post PRK
      and LASIK. In patients with myopic astigmatism who underwent LASIK and PRK,
      95.2%, and 96.3% of the patients reached their preoperative best corrected
      distance visual acuity at the final one year follow up visit post LASIK and PRK,
      respectively. The efficacy and safety indices were 1.00 or more for all groups
      with no eye lost any line of best corrected distance visual acuity. Conclusion:
      Our study results confirm the excellent efficacy, safety, good predictability and
      stability of myopia / myopic astigmatism correction by either wavefront-
      optimized LASIK or PRK over 1-year follow-up without significant differences
      between them using the WaveLight(r) EX500 excimer laser system.

PMID- 30294394
TI  - Effectiveness of the "Create Sensitivity" Caring Model on Blood Glucose/
      Glycosylated Hemoglobin and Quality of Life in Patients With Type 2 Diabetes.
AB  - Objective: This study aimed to determine the effectiveness of the "Create
      Sensitivity" caring model on blood glucose/ glycosylated hemoglobin and quality
      of life in patients with type 2 Diabetes. Methods: This study enrolled 70
      patients from an educational hospital in Kurdistan, Iran. The model was
      implemented among the test group over a period of 3 months. Blood glucose/
      glycosylated hemoglobin and patients' quality of life were measured before and
      after intervention. Data were analyzed using version 21 of the statistical
      software SPSS. Results: After the intervention, significant differences existed
      between the test and control groups both in blood glucose levels (means, 146.4 +/
      51.3 mg/dl and 175.6 +/- 59.8 mg/dl, respectively; P=0.032) and in glycosylated
      hemoglobin (means, 67.89 +/- 13.34 mmol/mol and 80.03 +/- 17.234 mmol/mol,
      respectively; P= 0.002). Additionally, there was also a significant difference
      between the quality of life of the patients in test group (mean, 58.25 +/- 5.3)
      and that in the control group (mean, 47.02 +/- 4.5) (P= 0.0001). Conclusion: Use
      of this model was associated with reducing fasting blood glucose and glycosylated
      hemoglobin and increasing the total mean of quality of life in the patients in
      the test group. So, the application of this model is recommended.

PMID- 30294395
TI  - Structural and electronic properties of CdTe1-xSex films and their application in
      solar cells.
AB  - The performance improvement of conventional CdTe solar cells is mainly limited by
      doping concentration and minority carrier life time. Alloying CdTe with an
      isovalent element changes its properties, for example its band gap and behaviour
      of dopants, which has a significant impact on its performance as a solar cell
      absorber. In this work, the structural, optical, and electronic properties of
      CdTe1-xSex films are examined for different Se concentrations. The band gap of
      this compound changes with composition with a minimum of 1.40 eV for x = 0.3. We
      show that with increasing x, the lattice constant of CdTe1-xSex decreases, which
      can influence the solubility of dopants. We find that alloying CdTe with Se
      changes the effect of Cu doping on the p-type conductivity in CdTe1-xSex,
      reducing the achievable charge carrier concentration with increasing x. Using a
      front surface CdTe1-xSex layer, compositional, structural and electronic grading
      is introduced to solar cells. The efficiency is increased, mostly due to an
      increase in the short-circuit current density caused by a combination of lower
      band gap and a better interface between the absorber and window layer, despite a
      loss in the open-circuit voltage caused by the lower band gap and reduced charge
      carrier concentration.

PMID- 30294396
TI  - Risk factors for hospital readmission among Swedish older adults.
AB  - Introduction: Hospital readmissions of older persons are common and often
      associated with complex health problems. The objectives were to analyze risk
      factors for readmission within 30 days from hospital discharge. Methods: A
      prospective study with a multifactorial approach based on the population-based
      longitudinal Swedish Adoption/Twin Study of Aging (SATSA) was conducted. During 9
      years of follow-up, information on hospitalizations, readmissions and associated
      diagnoses were obtained from national registers. Logistic regression models
      controlling for age and sex were conducted to analyze risk factors for
      readmissions. Results: Of the 772 participants, [mean age 69.7 (+/- 11.1), 84
      (63%)] were hospitalized and among these 208 (43%) had one or several
      readmissions within 30 days during the follow-up period. Most of the readmissions
      (57%) occurred within the first week; mean days from hospital discharge to
      readmission was 7.9 (+/- 6.2). The most common causes of admission and
      readmission were cardiovascular diseases and tumors. Only 8% of the readmissions
      were regarded as avoidable admissions. In a multivariate logistic regression,
      falling within the last 12 months (OR 0.57, p = 0.039) and being a male (OR 1.84,
      p = 0.006) increased the risk of readmission. Conclusions: Most older persons
      that are readmitted return to hospital within the first week after discharge.
      Experiencing a fall was a particular risk factor of readmission. Preventive
      actions should preferably take place already at the hospital to reduce the
      numbers of readmission. Still, it should be remembered that most readmissions
      were considered to be necessary.

PMID- 30294397
TI  - Urinary tract infections in a geriatric sub-acute ward-health correlates and
      atypical presentations.
AB  - Purpose: Bacterial urinary tract infections (UTIs) are the most frequently
      occurring infectious diseases in the geriatric population. The aim of the study
      was to determine the prevalence and clinical features of UTIs in geriatric in
      patients and their association with health and functional ability
      characteristics. Methods: A prospective cross-sectional cohort study was
      conducted among patients hospitalized on the geriatric ward. Patients were
      interviewed, examined, and had their hospital records analyzed. An uncontaminated
      midstream urine sample was collected and cultured in all of the cases suspected
      for UTI. Relative risks for UTI were counted and multivariable logistic
      regression model was built. Results: 246 patients were included, 179 (72.8%)
      women, 210 (85.4%) 75 + -year-olds. Bacterial UTIs occurred in 18.3% of the
      patients. The main etiological agent was Escherichia coli (73.3%). The most
      significant predictors of UTI were recurrent UTI and urinary catheter. The
      typical clinical UTI symptoms occurred in less than half of the cases (only in
      11.1% of cases fever was observed). More often, than in patients without UTIs,
      they reported symptoms such as delirium (28.9% vs. 18%), tachycardia (11.1% vs.
      1.5%) or hypotension (20% vs. 12.1%). Conclusions: Bacterial UTIs affect about
      1/5 of hospitalized geriatric patients. The clinical picture of these infections
      very often is atypical and it indicates a need for diagnostic vigilance.

PMID- 30294398
TI  - Utilization of medical rehabilitation services among older Poles: results of the
      PolSenior study.
AB  - Background: Rehabilitation tailored to older adults' needs might improve their
      functional performance and quality of life, as well as increase social
      participation. The aim of the study was to evaluate the use of medical
      rehabilitation services among older Poles in relation to socio-economic and
      health-related determinants. Materials and methods: Data regarding medical
      rehabilitation were obtained from the nationwide, multidisciplinary PolSenior
      project (2007-2012) conducted on representative sample of 4813 respondents (48.3%
      women) aged 65+ years. Socio-economic status, physical functioning, falls,
      chronic pain, and formal disability occurrence, as well as self-rated health were
      accounted for. Results: One in six respondents (18.9% women vs. 15.8% men, p <
      0.005) underwent medical rehabilitation during 12 months prior to the survey.
      Respondents mostly received electrotherapy or light radiation therapy (61.3%).
      Multivariate logistic regression analysis revealed that women aged 80+ years and
      men aged 90+ years had a significantly lower chance of using rehabilitation
      services compared to the youngest study participants (65-69 y.o.). City dwellers
      used rehabilitation services nearly twice as frequently as rural dwellers.
      Respondents with university education level were most likely to take part in
      these services. Dependence in IADL decreased participation in medical
      rehabilitation, while formal disability and chronic pain promoted utilization of
      rehabilitation services. Conclusions: Younger age, city dwelling, higher
      education, functional independence, formal disability certificate, and chronic
      pain increased participation in medical rehabilitation. Such results of the study
      should be considered in planning actions towards reducing health inequalities at
      the national level and promoting health and well-being among older adults.

PMID- 30294399
TI  - Clinical factors increasing discrepancies of renal function assessment with MDRD
      and Cockcroft-Gault equations in old individuals.
AB  - Abstract: In a daily clinical practice, glomerular filtration rate (GFR) is still
      estimated on the basis of short MDRD formula, whereas medications' Summaries of
      Product Characteristics suggest that GFR used for the dosage adjustment should be
      estimated based on the Cockcroft-Gault (C-G) equation. The aim of the study was
      to compare eGFR values calculated on the basis of short and full MDRD and C-G
      equations in PolSenior study participants with decreased eGFR. Methods: We have
      assessed differences in the estimation of GFR between short and full MDRD, as
      well as C-G formula, all equations utilizing non-isotope-dilution mass
      spectrometry-calibrated measurements of serum creatinine, in the community-based
      population of 760 persons aged 65 years or above (mean age 82 +/- 8 years) with
      estimated GFR < 60 ml/min/1.73 m2 (according to short MDRD). In addition, in our
      analysis, we have included the detailed characteristics of comorbidities and
      different aspects of mobility and functional performance. Results: The better
      concordance, precision, and accuracy with MDRD short formula were found for
      MDRDfull than C-G equation. In logistic regression analysis, female gender,
      activities in daily living (ADL) <= 4, and age > 80 years diminished, while
      visceral obesity improved accuracy (P30) of eGFR calculated according to C-G
      equation as compared to MDRDshort. Similar analysis did not found factors
      influencing P30 for MDRDfull equation. Conclusions: In very old subjects,
      especially females, dependent patients and those with visceral obesity,
      estimation of GFR based on short MDRD formula should not be used interchangeably
      with Cockcroft-Gault equation for the medicines dose tailoring.

PMID- 30294401
TI  - Chylothorax in Patients with Chronic Lymphocytic Leukemia: A Case Series.
AB  - Chylothorax, which is defined as the presence of chyle in the pleural space, is
      often caused by malignancy. However, chylothorax as a result of underlying CLL is
      exceedingly rare in the literature. Chyle contains fat soluble vitamins and
      lymphocytes, meaning that its collection into the pleural space may further
      exacerbate the immunosupressed state of an individual with CLL. Here, we report
      three cases of patients with CLL who developed chylothorax, and their management.
      Chylothorax, although rare with CLL, should be considered in the differential
      diagnosis when patients with CLL present with pleural effusions, especially if
      recurrent. Discovery of a chylothorax may indicate the need for further treatment
      of CLL.

PMID- 30294402
TI  - Perihepatic abscesses caused by dropped appendicoliths in a child.
AB  - A dropped appendicolith is a well-known complication of laparoscopic appendectomy
      that may occur because of stone expulsion from the appendix, before or during
      surgery, and typically manifests as a focal, subcentimeter area of high
      attenuation with or without associated abscess. Dropped appendicoliths may act as
      niduses for infection and may result in the future development of abscess
      formation. We report the case of a 10-year-old pediatric patient who developed 2
      perihepatic abscesses caused by 2 appendicoliths that were inadvertently dropped
      during laparoscopic surgery.

PMID- 30294400
TI  - Antipsychotic Drug Dispensations in Older Adults, Including Continuation After a
      Fall-Related Hospitalization: Identifying Adherence to Screening Tool of Older
      Persons' Potentially Inappropriate Prescriptions Criteria Using the Nova Scotia
      Seniors' Pharmacare Program and Canadian Institute for Health's Discharge
      Databases.
AB  - Purpose: Despite well-established concerns regarding adverse drug effects,
      antipsychotics are frequently prescribed for older adults. Our first objective
      was to identify trends in antipsychotic dispensations to older Nova Scotians.
      STOPP (Screening Tool of Older Persons' Potentially Inappropriate Prescriptions)
      criteria identify antipsychotic use in those with a history of falls as
      potentially inappropriate. Our second objective was to identify trends,
      predictors, and adherence with this STOPP criteria by identifying continued
      antipsychotic dispensations following a fall-related hospitalization. Methods: A
      descriptive cross-sectional cohort study of Nova Scotia Seniors' Pharmacare
      Program (NSSPP) beneficiaries >= 66 years with at least one antipsychotic
      dispensation annually from April 1, 2009 to March 31, 2014 was completed. As
      well, unique beneficiaries with at least one antipsychotic dispensation in the
      four-year period between April 1, 2009 and March 31, 2013 were linked to fall
      related hospitalizations recorded in the Canadian Institute for Health
      Information Discharge Abstract Database. The relationship of age, sex, fiscal
      year, days supply and length-of-stay were studied to identify predictors of
      continued antipsychotic dispensation post-discharge. Descriptive statistics and
      multivariate logistic analysis were performed. Odds ratios for the association of
      risk factors and adherence to STOPP criteria were calculated. Findings: We
      identified that in each year observed, there were 6% of eligible NSSPP
      beneficiaries that received at least one antipsychotic dispensation.
      Approximately 70% of antipsychotic dispensations were for second generation
      agents, primarily quetiapine and risperidone. Of the unique beneficiaries with at
      least one antipsychotic dispensation in the four-year period between April 1,
      2009 and March 31, 2013 who survived a fall-related hospitalization over 75% were
      dispensed an antipsychotic in the 100 days following hospital discharge. Logistic
      regression showed no statistically significant association between potentially
      inappropriate therapy and potential predictors in multivariate analysis.
      Implications: In each year from 2009 to 2014, 6% of Nova Scotia Seniors'
      Pharmacare beneficiaries were dispensed at least one antipsychotic prescription.
      Over 75% of the older adults who received an antipsychotic dispensation in the
      100 days prior to a fall-related hospitalization, continued the drug class after
      discharge. This demonstrates that despite the recommendations of quality
      indicators such as the STOPP criteria, antipsychotics are continued in
      individuals at a high risk of falling. Future investigations are needed to inform
      health team, system, and policy interventions to improve concordance with this
      antipsychotic specific STOPP criterion when appropriate.

PMID- 30294403
TI  - Luxury perfusion: A paradoxical finding and pitfall of CT perfusion in subacute
      infarction of brain.
AB  - In the context of recent guidelines for stroke management, application of
      computed tomographic perfusion (CTP) is anticipated to increase, especially
      within 6-24 hours after stroke onset. There are commercially available software
      packages to help to detect the infarct core and the penumbra, however, the
      results of these software are not always straightforward that might cause
      incorrect CTP interpretation. We present here a case of acute ischemic stroke in
      which the CTP software misinterpreted the results by labeling the normal
      hemisphere as infarction and ischemia due to luxury perfusion of the infarcted
      hemisphere. Awareness of laterality of the patient's symptoms and the
      understanding of functioning of perfusion analysis software is necessary to avoid
      this pitfall.

PMID- 30294404
TI  - COMPLEX-VALUED TIME SERIES MODELING FOR IMPROVED ACTIVATION DETECTION IN FMRI
      STUDIES.
AB  - A complex-valued data-based model with pth order autoregressive errors and
      general real/imaginary error covariance structure is proposed as an alternative
      to the commonly-used magnitude-only data-based autoregressive model for fMRI time
      series. Likelihood-ratio-test-based activation statistics are derived for both
      models and compared for experimental and simulated data. For a dataset from a
      right-hand finger-tapping experiment, the activation map obtained using complex
      valued modeling more clearly identifies the primary activation region (left
      functional central sulcus) than the magnitude-only model. Such improved accuracy
      in mapping the left functional central sulcus has important implications in
      neurosurgical planning for tumor and epilepsy patients. Additionally, we develop
      magnitude and phase detrending procedures for complex-valued time series and
      examine the effect of spatial smoothing. These methods improve the power of
      complex-valued data-based activation statistics. Our results advocate for the use
      of the complex-valued data and the modeling of its dependence structures as a
      more efficient and reliable tool in fMRI experiments over the current practice of
      using only magnitude-valued datasets.

PMID- 30294406
TI  - Double Sparsity Kernel Learning with Automatic Variable Selection and Data
      Extraction.
AB  - Learning in the Reproducing Kernel Hilbert Space (RKHS) has been widely used in
      many scientific disciplines. Because a RKHS can be very flexible, it is common to
      impose a regularization term in the optimization to prevent overfitting. Standard
      RKHS learning employs the squared norm penalty of the learning function. Despite
      its success, many challenges remain. In particular, one cannot directly use the
      squared norm penalty for variable selection or data extraction. Therefore, when
      there exists noise predictors, or the underlying function has a sparse
      representation in the dual space, the performance of standard RKHS learning can
      be suboptimal. In the literature, work has been proposed on how to perform
      variable selection in RKHS learning, and a data sparsity constraint was
      considered for data extraction. However, how to learn in a RKHS with both
      variable selection and data extraction simultaneously remains unclear. In this
      paper, we propose a unified RKHS learning method, namely, DOuble Sparsity Kernel
      (DOSK) learning, to overcome this challenge. An efficient algorithm is provided
      to solve the corresponding optimization problem. We prove that under certain
      conditions, our new method can asymptotically achieve variable selection
      consistency. Simulated and real data results demonstrate that DOSK is highly
      competitive among existing approaches for RKHS learning.

PMID- 30294405
TI  - Role of Serological Tests in the Diagnosis of Mold Infections.
AB  - Purpose of Review: To understand the role of antibody detection in the diagnosis
      of infections caused by filamentous fungi (molds). Rapid and accurate profiling
      of infection-causing fungal pathogens remains a significant challenge in modern
      health care. Classical fungal culture and serology continue to be relevant even
      though over the past few decades, antigen (biomarker) assays such as ELISA and
      lateral flow devices have been developed and validated. Recent Findings: This
      article reviews the current antibody detection systems (serological tests) for
      the diagnosis of mold infections associated with pulmonary disease and introduces
      new developments. Classic and more recently developed serological techniques and
      their performance characteristics, including immunodiffusion, complement
      fixation, and ELISA. Summary: The diseases covered are allergic bronchopulmonary
      aspergillosis, chronic pulmonary aspergillosis, invasive aspergillosis,
      mucormycosis, diseases caused by filamentous basidiomycetes, infection caused by
      Talaromyces marneffei and pythiosis. Serology remains a cornerstone for fungal
      diagnostic testing.

PMID- 30294407
TI  - The effect of shear waves in an elastic sphere on the radiation force from a
      quasi-Gaussian beam.
AB  - Ultrasound beams are capable of exerting radiation force on scattering or
      absorbing obstacles. Previously, our team developed a technology to reposition
      kidney stones using this approach. It is convenient to study the influence of
      different parameters using a theoretical model based on a spherical shape stone
      and a quasi-Gaussian acoustic beam. In such an approach, only two geometrical
      parameters are involved, namely the beam width and the sphere diameter. The
      radiation force depends on their ratio, as well as on the elastic properties of
      the liquid and the stone. In this work, numerical modeling was performed to
      calculate the force acting on an elastic sphere using previously developed
      theory. Our numerical modeling indicates that the force on a stone is strongest
      when the beam is slightly wider than the stone. Also, the force created by a
      narrow beam appears to be the strongest when the beam is targeted to the side of
      the sphere. These peculiarities of the radiation force are explained by more
      effective generation of shear waves inside the stone resulting from their
      effective coupling with the acoustic waves in liquid at the stone edge.

PMID- 30294408
TI  - Non-Uniform Microphone Arrays for Robust Speech Source Localization for
      Smartphone-Assisted Hearing Aid Devices.
AB  - Robust speech source localization (SSL) is an important component of the speech
      processing pipeline for hearing aid devices (HADs). SSL via time direction of
      arrival (TDOA) estimation has been known to improve performance of HADs in noisy
      environments, thereby providing better listening experience for hearing aid
      users. Smartphones now possess the capability to connect to the HADs through
      wired or wireless channel. In this paper, we present our findings about the non
      uniform non-linear microphone array (NUNLA) geometry for improving SSL for HADs
      using an L-shaped three-element microphone array available on modern smartphones.
      The proposed method is implemented on a frame-based TDOA estimation algorithm
      using a modified Dictionary-based singular value decomposition method (SVD)
      method for localizing single speech sources under very low signal to noise ratios
      (SNR). Unlike most methods developed for uniform microphone arrays, the proposed
      method has low spatial aliasing as well as low spatial ambiguity while providing
      a robust low-error with 360 degrees  DOA scanning capability. We present the
      comparison among different types of microphone arrays, as well as compare their
      performance using the proposed method.

PMID- 30294409
TI  - New Trends in Quantitative Nuclear Cardiology Methods.
AB  - Purpose of review: The use of quantitative analysis in single photon emission
      computed tomography (SPECT) and positron emission tomography (PET) has become an
      integral part of current clinical practice and plays a crucial role in the
      detection and risk stratification of coronary artery disease. Emerging
      technologies, new protocols, and new quantification methods have had a
      significant impact on the diagnostic performance and prognostic value of nuclear
      cardiology imaging, while reducing the need for clinician oversight. In this
      review, we aim to describe recent advances in automation and quantitative
      analysis in nuclear cardiology. Recent Findings: Recent publications have shown
      that fully automatic processing is feasible, limiting human input to specific
      cases where aberrancies are detected by the quality control software.
      Furthermore, there is evidence indicating that fully quantitative analysis of
      myocardial perfusion imaging is feasible and can achieve at least similar
      diagnostic accuracy as visual interpretation by an expert clinician. In addition,
      the use of fully automated quantification in combination with machine learning
      algorithms can provide incremental diagnostic and prognostic value over the
      traditional method of expert visual interpretation. Summary: Emerging
      technologies in nuclear cardiology focus on automation and the use of artificial
      intelligence as part of the interpretation process. This review highlights the
      benefits and limitations of these applications, and outlines future directions in
      the field.

PMID- 30294410
TI  - Cancer-related cognitive impairment in breast cancer survivors: An examination of
      conceptual and statistical cognitive domains using principal component analysis.
AB  - There is a great deal of variability in the composition of neuropsychological
      test batteries used in the assessment of cancerrelated cognitive impairment
      (CRCI). Not only the development of a gold standard approach for CRCI assessment
      would allow for easier identification of women suffering from CRCI but it would
      also promote optimal care for survivors. As a first step towards the development
      of a valid and reliable unified test battery, the objective of this study was to
      verify whether the theoretical domains commonly used in CRCI assessment are
      statistically supported, before and after breast cancer treatment. Principal
      component analyses (PCA) were performed on the results from 23 neuropsychological
      tests grouped into eight conceptual domains. For baseline data, the Kaiser-Meyer
      Olkin was .82 and Bartlett's X2(253, N=95) = 949.48, P<0.001. A five-component
      solution explained 60.94% of the common variance. For the post-treatment data,
      the Kaiser-Meyer-Olkin was .83 and Bartlett's X2(253, N=95) = 1007.21, P<0.001
      and a five component solution explained 62.03% of the common variance. Although a
      visual comparison of the theoretical model with those determined via PCA
      indicated important overlap between conceptual domains and statistical
      components, significant dissimilarities were also observed.

PMID- 30294411
TI  - Light-induced decarboxylation in a photo-responsive iron-containing complex based
      on polyoxometalate and oxalato ligands.
AB  - A new photoresponsive molecular polyanion in which two Fe(iii) ions are
      simultaneously coordinated by two [A-alpha-PW9O34]9- polyoxometalate units and
      two oxalato ligands has been obtained. When irradiated with UV light its
      potassium salt, 1, exhibits a remarkable photocoloration effect, attributable to
      the partial reduction of the POM units to give rise to a mixed-valence species.
      The photoinduced process is intramolecular and involves electron transfer from
      the oxalato ligands, which partially decompose releasing CO2, towards the Fe(iii)
      and the POM. This mechanism has been confirmed by DRS, IR, XPS and Mossbauer
      spectroscopy, magnetism and elemental analysis. An analogous derivative of 1
      containing malonato ligands does not exhibit such photoactive behaviour, which is
      evidence that the oxalate ligand is essential for the photoactivity of 1. To our
      knowledge, 1 represents the first POM-based compound in which the photocoloration
      effect does not require the presence of intermolecular short interactions.

PMID- 30294412
TI  - Correction: Bioinspired M-13 bacteriophage-based photonic nose for differential
      cell recognition.
AB  - [This corrects the article DOI: 10.1039/C6SC02021F.].

PMID- 30294413
TI  - Erratum: Further correction: Cobalt co-catalysis for cross-electrophile coupling:
      diarylmethanes from benzyl mesylates and aryl halides.
AB  - [This corrects the article DOI: 10.1039/C4SC03106G.].

PMID- 30294414
TI  - Correction: Hypoxia inducible factor (HIF) as a model for studying inhibition of
      protein-protein interactions.
AB  - [This corrects the article DOI: 10.1039/C7SC00388A.].

PMID- 30294415
TI  - Correction: A simple and traceless solid phase method simplifies the assembly of
      large peptides and the access to challenging proteins.
AB  - [This corrects the article DOI: 10.1039/C7SC01912B.].

PMID- 30294416
TI  - Correction: Tailored theranostic apolipoprotein E3 porphyrin-lipid nanoparticles
      target glioblastoma.
AB  - [This corrects the article DOI: 10.1039/C7SC00732A.].

PMID- 30294417
TI  - Supercooling of functional alkyl-pi molecular liquids.
AB  - Metastable states of soft matters are extensively used in designing stimuli
      responsive materials. However, the non-steady properties may obstruct consistent
      performance. Here we report an approach to eradicate the indistinguishable
      metastable supercooled state of functional molecular liquids (FMLs), which
      remains as a liquid for weeks or months before crystallizing, via rational
      molecular design. The phases (solid, kinetically stable liquid, and supercooled
      liquid) of a model FML, branched alkyl chain-substituted 9,10-diphenylanthracene
      (DPA), are found to be governed by subtle alterations of the molecular structure
      (alkyl-DPA ratio and bulkiness of the DPA unit). We thus outline molecular design
      principles to avoid supercooled FML formation. Moreover, we demonstrate a
      practical technique to rapidly discriminate supercooled FMLs (within 5 h) by
      accelerating their crystallization in differential scanning calorimetry heating
      via pre-annealing or relatively slow scanning.

PMID- 30294418
TI  - Facile room temperature synthesis of large graphene sheets from simple molecules.
AB  - The largest graphene sample obtained through a chemical reaction under ambient
      conditions (temperature and pressure), using simple molecules such as benzene or
      n-hexane as precursors, is reported. Starting from a heterogeneous reaction
      between solid iron chloride and the molecular precursor (benzene and n-hexane) at
      a water/oil interface, graphene sheets with micrometric lateral size are obtained
      as a film deposited at the liquid/liquid (L/L) interface. The pathway involving
      the cyclization and aromatization of n-hexane to benzene at the L/L interface,
      and the sequence of conversion of benzene to biphenyl and biphenyl to condensed
      rings (which originates the graphene structures) was followed by different
      characterization techniques and a mechanistic proposal is presented. Finally, we
      demonstrate that this route can be extended for the synthesis of N-doped
      graphene, using pyridine as the molecular precursor.

PMID- 30294419
TI  - Direct evidence for heme-assisted solid-state electronic conduction in multi-heme
      c-type cytochromes.
AB  - Multi-heme cytochrome c (Cytc) proteins are key for transferring electrons out of
      cells, to enable intracellular oxidation to proceed in the absence of O2. In
      these proteins most of the hemes are arranged in a linear array suggesting a
      facile path for electronic conduction. To test this, we studied solvent-free
      electron transport across two multi-heme Cytc-type proteins: MtrF (deca-heme
      Cytc) and STC (tetra-heme Cytc). Transport is measured across monolayers of these
      proteins in a solid state configuration between Au electrodes. Both proteins
      showed 1000* higher conductance than single heme, or heme-free proteins, but
      similar conductance to monolayers of conjugated organics. Conductance is found to
      be temperature-independent (320-80 K), suggesting tunneling as the transport
      mechanism. This mechanism is consistent with I-V curves modelling, results of
      which could be interpreted by having protein-electrode coupling as rate limiting,
      rather than transport within the proteins.

PMID- 30294420
TI  - Genome mining, isolation, chemical synthesis and biological evaluation of a novel
      lanthipeptide, tikitericin, from the extremophilic microorganism
      Thermogemmatispora strain T81.
AB  - Genome mining of the New Zealand extremophilic microorganism Thermogemmatispora
      strain T81 indicated the presence of biosynthetic machinery to produce several
      different peptidic natural products. Solid-phase culture of T81 led to the
      isolation of tikitericin 1, a new lanthipeptide characterised by four
      (methyl)lanthionine bridges. The mass-guided isolation and structural elucidation
      of tikitericin 1 is described together with its total synthesis via Fmoc-solid
      phase peptide synthesis (SPPS). The key non-canonical (methyl)lanthionine
      residues were synthesised in solution phase via an improved synthetic route and
      subsequently assembled to construct the peptide backbone using Fmoc-SPPS. N
      Terminal truncated analogues of tikitericin (2-5) were also prepared in order to
      evaluate the contribution of each sequential ring of the polycyclic lanthipeptide
      to the antibacterial activity.

PMID- 30294421
TI  - Copper catalyzed photoredox synthesis of alpha-keto esters, quinoxaline, and
      naphthoquinone: controlled oxidation of terminal alkynes to glyoxals.
AB  - Herein, we report a facile visible light induced copper catalyzed controlled
      oxidation of terminal C[triple bond, length as m-dash]C alkynes to alpha-keto
      esters and quinoxalines via formation of phenylglyoxals as stable intermediates,
      under mild conditions by using molecular O2 as a sustainable oxidant. The current
      copper catalysed photoredox method is simple, highly functional group compatible
      with a broad range of electron rich and electron poor aromatic alkynes as well as
      aliphatic alcohols (1 degrees , 2 degrees  and 3 degrees  alcohols), providing an
      efficient route for the preparation of alpha-keto esters (43 examples),
      quinoxaline and naphthoquinone with higher yields than those in the literature
      reported thermal processes. Furthermore, the synthetic utility of the products
      has been demonstrated in the synthesis of two biologically active molecules, an
      E. coli DHPS inhibitor and CFTR activator, using the current photoredox process.
      In addition, we applied this methodology to the one-pot synthesis of a
      heterocyclic compound (quinoxaline, an FLT3 inhibitor) by trapping the
      intermediate phenylglyoxal with O-phenylenediamine. The intermediate
      phenylglyoxal can also be isolated and further reacted with an internal alkyne to
      form naphthoquinone. This process can be readily scaled up to the gram scale.

PMID- 30294422
TI  - Hyaluronic acid hydrogel scaffolds loaded with cationic niosomes for efficient
      non-viral gene delivery.
AB  - The lack of ideal non-viral gene carriers has motivated the combination of
      delivery systems and tissue-engineered scaffolds, which may offer relevant
      advantages such as enhanced stability and reduced toxicity. In this work, we
      evaluated a new combination between niosome non-viral vectors and hyaluronic acid
      (HA) hydrogel scaffolds, both widely studied due to their biocompatibility as
      well as their ability to incorporate a wide variety of molecules. We evaluated
      three different niosome formulations (niosomes 1, 2 and 3) varying in composition
      of cationic lipid, helper lipid and non-ionic tensioactives. Niosomes and
      nioplexes obtained upon the addition of plasmid DNA were characterized in terms
      of size, polydispersity, zeta potential and ability to transfect mouse bone
      marrow cloned mesenchymal stem cells (mMSCs) in 2D culture. Niosome 1 was
      selected for encapsulation in HA hydrogels due to its higher transfection
      efficiency and the formulation was concentrated in order to be able to
      incorporate higher amounts of DNA within HA hydrogels. Nioplex-loaded HA
      hydrogels were characterized in terms of biomechanical properties, particle
      distribution, nioplex release kinetics and ability to transfect encapsulated
      mMSCs in 3D culture. Our results showed that nioplex-loaded HA hydrogel scaffolds
      presented little or no particle aggregation, allowed for extensive cell spreading
      and were able to efficiently transfect encapsulated mMSCs with high cellular
      viability. We believe that the knowledge gained through this in vitro model can
      be utilized to design novel and effective platforms for in vivo local and non
      viral gene delivery applications.

PMID- 30294423
TI  - Generation of controllable gaseous H2S concentrations using microfluidics.
AB  - Hydrogen sulfide (H2S) plays an important role as an intercellular and
      intracellular signaling molecule, yet its targets are not well understood. As a
      molecule it easily evaporates and it is hard to acquire stable concentration for
      in vitro studies, constituting a major problem for the field to identify its
      downstream targets and function. Here we develop a microfluidic system that can
      provide consistent and controllable H2S levels in contrast to the current method
      of delivering large bolus doses to cells. The system relies on the permeability
      of H2S gas through a polydimethylsiloxane thin membrane. A hydrogen sulfide
      donor, sodium hydrosulfide, is perfused in the microchannels below the gas
      permeable membrane and gaseous H2S diffuses across the membrane, providing a
      stable concentration for up to 5 hours. Using electrochemical sensors within 3
      ppm range, we found that H2S concentration was dependent on two parameters, the
      concentration of H2S donor, sodium hydrosulfide and the flow rate of the solution
      in the microchannels. Additionally, different H2S concentration profiles can be
      obtained by alternating the flow rate, providing an easy means to control the H2S
      concentration. Our approach constitutes a unique method for H2S delivery for in
      vitro and ex vivo studies and is ideally suited to identify novel biological
      processes and cellular mechanisms regulated by H2S.

PMID- 30294424
TI  - A framework to determine when liver transplantation is futile.

PMID- 30294425
TI  - Infographic: Reporting the right information for stem cell studies is important.

PMID- 30294426
TI  - Is patellofemoral pain a precursor to osteoarthritis?: Patellofemoral
      osteoarthritis and patellofemoral pain patients share aberrant patellar shape
      compared with healthy controls.
AB  - Objectives: It has been hypothesized that patellofemoral pain, a common knee
      condition in adolescents and young adults, may be a precursor of degenerative
      joint changes and may ultimately lead to patellofemoral osteoarthritis. Since
      both conditions share several mechanical disease characteristics, such as altered
      contact area between the femur and patella and increased joint stress, we
      investigated whether these conditions share similar and different shape
      characteristics of the patella compared with normal controls. Methods: This cross
      sectional study compared three different study populations: 32 patellofemoral
      pain subjects (mean age, 32 years (22 to 45); 72% female); 56 isolated
      radiological patellofemoral osteoarthritis subjects (mean age, 54 years (44 to
      58); 89% female); and 80 healthy control subjects (mean age, 52 years (44 to 58);
      74% female). Measurements included questionnaires, and lateral and skyline
      radiographs of the knee. Two separate 30-point 2D statistical shape models of the
      patella were created from the lateral and skyline radiographs. A general linear
      model was used to test for differences in standardized shape modes (a specific
      shape variant of the patella) between patellofemoral osteoarthritis,
      patellofemoral pain, and controls, using Bonferroni correction and adjustment for
      body mass index and gender. Results: Five shape modes showed statistically
      significant differences between groups: skyline modes 1 (p < 0.001), 8 (p =
      0.004), and 10 (p < 0.001); and lateral modes 5 (p = 0.002) and 7 (p = 0.002).
      Skyline mode 8 and lateral mode 5 were similar for patellofemoral osteoarthritis
      and patellofemoral pain populations, while being statistically significant
      different from the control group. Conclusion: Our results indicate that
      patellofemoral pain and patellofemoral osteoarthritis share similar shape
      characteristics, which are different from control subjects. These findings
      support the proposed continuum disease model of patellofemoral pain predisposing
      to the development of patellofemoral osteoarthritis.Cite this article: J. F. A.
      Eijkenboom, J. H. Waarsing, E. H. G. Oei, S. M. A. Bierma-Zeinstra, M. van
      Middelkoop. Is patellofemoral pain a precursor to osteoarthritis? Patellofemoral
      osteoarthritis and patellofemoral pain patients share aberrant patellar shape
      compared with healthy controls. Bone Joint Res 2018;7:541-547. DOI: 10.1302/2046
      3758.79.BJR-2018-0112.R1.

PMID- 30294427
TI  - Bilirubin, urobilinogen, pancreas elastase and bile acid in drain fluid. The GBUP
      study: Analysis of biomarkers for a colorectal anastomotic leakage.
AB  - Purpose: A colorectal anastomotic leakage (CAL) is a major complication after
      colorectal surgery and leads to high rates of morbidity and prolonged hospital
      stay. The study aims to evaluate the benefit of using bilirubin, urobilinogen,
      pancreas elastase and bile acid in the drain fluid (DF) as a predictive marker
      for the CAL. Methods: From June 2015 to October 2017 100 patients, who underwent
      left hemicolectomy (LH), sigma resection (SR), high anterior resection (HAR), low
      anterior resection (LAR) or reversal of Hartmann's Procedure (ROHP) were included
      in this monocentric non-randomized prospective clinical trial. During the first
      four postoperative days (POD) the concentration of bilirubin, urobilinogen,
      pancreas elastase and bile acid in the DF was measured. Results: In total 100
      patients were recruited. 17 were excluded due to intraoperative decisions to
      conduct a protective stoma. 6 patients had a CAL. The patients of the control
      group (n = 77) and the patients who suffered from a CAL (n = 6) had no increased
      concentration of urobilinogen and pancreas elastase in the DF. The concentration
      of bile acid in the DF of the patients who suffered from a CAL differed from
      those of the control group on the 4th POD (p = 0.055).The concentration of
      bilirubin in the DF of the patients who suffered from a CAL significantly
      differed from those of the control group on the 1st POD (p = 0.031) and on the
      3rd POD (p = 0.041). Conclusion: Bilirubin and bile acid in the DF may function
      as a predictive marker for a CAL.

PMID- 30294428
TI  - A novel device in parathyroid autotransplantation for 6 patients with secondary
      hyperparathyroidism - Case series.
AB  - Background: Secondary hyperparathyroidism(sHPT) is one of the most serious
      complications in long-term hemodialysis patients. Patients may suffer from
      metabolic bone diseases, severe atherosclerosis and undesirable cardiovascular
      events. Endoscopic parathyroidectomy with autotransplantation is a treatment
      option for those who do not respond to clinical management. Methods: 6 patients
      with secondary hyperparathyroidism were treated with endoscopic parathyroidectomy
      and autotransplantation. Pieces of parathyroid tissue were squeezed in our novel
      self-made device and injected into brachioradialis. Results: Preoperative
      symptoms were alleviated, and the serum PTH and alkaline phosphatase levels,
      hyperphosphatemia, and hypercalcemia were improved or normalized in all 6
      patients. The preparation time of parathyroid fragments for autotransplantation
      was less than 10 min in all 6 patients.Pathological examinations revealed
      parathyroid cells remains active. Conclusion: Application of the novel squeezing
      device is an economic, effective and safe way in endoscopic parathyroidectomy and
      autotransplantation for patients with secondary hyperparathyroidism.

PMID- 30294429
TI  - A single epitope of Epstein-Barr Virus stimulate IgG production in mice.
AB  - Background: Epstein-Barr virus (EBV) is closely associated with the high
      incidence of nasopharyngeal carcinoma in worldwide. Vaccination is one strategy
      with the potential to prevent the occurrence of EBV-associated cancers, but a
      suitable vaccine is yet to be licensed. Much vaccine development research focuses
      on the GP350/220 protein of EBV as it contains an immunogenic epitope at residues
      147-165, which efficiently stimulates IgG production in vitro. We examined the
      ability of this epitope (EBVepitope) to induce IgG production in mice. Methods:
      The antibody binding pattern of the epitope was analyzed using bioinformatics
      tools. The IgG production in mice were examined by FACS CaliburTM Flow cytometer.
      Results: The epitope bound the 72A1 monoclonal antibody at the same site as
      GP350/220 protein, indicating that the epitope should stimulate B cells to
      produce antibody. Moreover, in vivo administration of EBVepitope successfully
      induced IgG expression from B cells, compared with controls. Further
      investigation indicated that the relative number of B cells expressing IgE in
      EBVepitope-treated mice was lower than controls. Conclusions: Our data suggest
      that this EBV GP350 epitope is able to induce IgG expression in vivo without
      causing allergic reactions, and represents a potential EBV vaccine candidate.

PMID- 30294430
TI  - A new clinical-ultrasound score to predict difficult
      videolaparocholecystectomies: A prospective study.
AB  - Background: The gold standard treatment of symptomatic cholelithiasis is
      videolaparoscopic cholecystectomy (VLC). The aim of this study is to produce a
      predictive clinical ultrasound (US) score for difficult VLC to reduce the rate of
      conversion to open cholecystectomy surgery and intra and/or post-operative
      complications. Methods: In this prospective study carried out in 2017 we enrolled
      135 patients (pts) who underwent VLC in our General Surgery Unit. A specific pre
      operative abdominal ultrasound scan was performed to assess gallbladder
      characteristics for each patient. All US and patients' characteristics were
      recorded in a standard form in order to obtain a preoperative score and were then
      added to the intra-operative variables. Results: The analysis revealed a
      statistical significance between post-operative characteristics and parietal
      thickness, adhesions, stratifications and volume of gallstones. Comparing the
      degree of difficulty VLC assessed in the pre-operative stage to the
      intraoperative score, the sensitivity of the preoperative US scan test is 91.8%
      while the specificity is 76.7%. Conclusions: The variables which proved
      statistically significant in predicting a difficult cholecystectomy were: age,
      parietal thickness >3 mm, adhesions, stratifications, gallstones >2 cm and fixed
      gallstones. We have definitively defined a predictive score for difficult VLC for
      which a VLC is to be considered potentially difficult whenever it presents a pre
      operative score equal or greater than 4 (and a "easy" one with a pre-operative
      score less than 4). These findings may prove helpful in further reducing the
      conversion rate and the rate of intra- and/or post-operative complications.

PMID- 30294431
TI  - Case report: Laparoscopic approach in the treatment of presacral lipoma.
AB  - Retrorectal lipoma, as well as other retrorectal tumours, is a relatively rare
      disorder. Retrorectal tumours accounted for 1 in 40,000 hospital admissions. We
      present a case of retrorectal lipoma, 15 cm * 10 cm * 8 cm in size, treated by
      the laparoscopic approach. The preoperative magnetic resonance imaging visualised
      a mass, 12 cm * 6.7 cm * 8.6 cm in diameter, in the retrorectal space, spreading
      toward the left obturator foramen. Surgery was indicated due to exclude malignant
      process certainly, because it is difficult to differentiate lipoma from low-grade
      liposarcoma on non invasive imaging. Laparoscopic extirpation of the tumour was
      performed. The overall operative time was 80 min. The diagnosis of lipoma was
      established on histological examination. The patient was discharged from hospital
      on the 2nd day after the surgery. We have found this minimally invasive operation
      to be an effective and well-tolerated treatment option, determined by the
      experience of the surgeon.

PMID- 30294432
TI  - Patient's views of the consent process for groin hernia repair: Use of consent
      template improves compliance with best practice (Original research).
AB  - Background: Informed consent obtained for day case surgery has been historically
      incomplete. An assessment of consenting practice for groin hernia was performed
      relative to existing gold standards and patient's perception of the consent
      process was evaluated with a questionnaire. The aim of the study was to identify
      areas of improvement to comply with best practice. Methods: A retrospective audit
      of adult patients undergoing groin hernia repair (June-November 2016) at a
      tertiary care centre was performed. The same cohort of patients was surveyed with
      a self-administered questionnaire to identify their view on consenting practice.
      Results: 113 patients were identified who underwent groin hernia repair during
      the study period. Pre-printed consent templates-stickers (as opposed to hand
      written) were used in 53(47%) cases. In 75(66%) cases, there was complete
      documentation of the risks and benefits of surgery. 81(72%) patients received
      information about the full benefits of surgery. 27(23%) patients received partial
      information and 7(6%) patients had no mention of benefit recorded. Postoperative
      recovery was fully explained to 85(75%) patients. Use of pre-printed templates
      ensured 100% documentation compared to handwritten consent forms (risks 37%,
      benefits 47%, and recovery 53%). Preference for the timing of consent was in
      clinic (64%), day of surgery (25%). 34(56%) felt the choice for the technique and
      22(36%) felt the choice for anaesthesia. Satisfaction was non-significantly
      better in those consented in clinic (87% versus 76% p = 0.74). 49(80%) felt happy
      with the overall consent process. 57(93%) felt that they received support and
      advice. 60(98%) responders felt confidence in the National Health Service and
      59(97%) would recommend treatment to family and friends. Conclusions: The use of
      pre-printed consent and discharge summary templates improve compliance with best
      practice. Whilst patient preference favours consent in the outpatient clinic,
      satisfaction levels were high wherever consent was obtained. Patients should have
      more choice.

PMID- 30294433
TI  - Does pisiform subluxation affect the postoperative outcomes in a cohort of
      patients with distal radius fractures?
AB  - Background: In this study, we retrospectively surveyed the presence or absence of
      pisiform subluxation in surgically treated distal radius fractures (DRF) cases.
      In addition, we investigated whether or not the postoperative short-term
      treatment outcome differs due to the presence of pisiform subluxation. Materials
      and methods: The subjects were 134 DRF patients treated with volar locking plate
      fixation (53 males and 81 females, mean age: 64 years old). The pisotriquetral
      joint was observed on a preoperative CT to investigate the presence or absence of
      pisiform subluxation according to the criteria reported by Vasilas. 134 patients
      divided into subluxation group and non-subluxation group, and the clinical
      outcomes were compared between these groups. Results: Pisiform subluxation was
      noted in 23.1% (31 patients, 15 males and 16 females, mean age 61 years). No
      significant difference was noted in patient background in both groups. The
      postoperative pronation angle in the non-subluxation group was significantly
      greater than that in the subluxation group, but there was no significant
      difference in any other parameter (the range of motion of the wrist, grip
      strengths, VAS, Q-DASH scores, and Mayo score) between these 2 groups. However it
      concomitantly occurred in 23.1% of DRF cases in our series, there was no
      significant difference in the postoperative treatment outcome between these 2
      groups. Conclusions: Therapeutic intervention of pisiform subluxation is
      unnecessary during treatment of DRF, since pisiform subluxation does not affect
      the postoperative clinical outcomes of distal radius fractures.

PMID- 30294434
TI  - Experimental comparative study of thrombogenicity of two differently luminal
      heparinized ePTFE vascular prosthetics.
AB  - Introduction: ; Heparin bonded grafts have proven to improve patency, at least
      transiently.Two different heparin bonded expanded polytetrafluoroethylene (ePTFE)
      grafts produced by different technologies are currently available.This pilot
      primary goal was to test these commonly used, but differently heparinized ePTFE
      grafts for differences in primary patency after a 6-months follow-up in a sheep
      model. Secondly, the aim was to establish a large animal model to enable future
      translational studies and further graft development. Method: ; End-to-side bypass
      of the common carotid artery was performed bilaterally in sheep. Either a Gore(r)
      Propaten heparinized graft or a Jotec(r) Flowline Bipore heparinized graft was
      used, both 5 mm in diameter.Following graft implantation, the sheep were kept on
      pasture for 6 months, with monthly duplex scans to determine patency. At
      termination, the grafts were duplex scanned a final time, with the animals
      sedated, and the grafts were removed for heparin activity analysis. Results: ; 14
      sheep were operated, 11 survived total follow-up time. At final follow-up, 4
      patent Gore(r) grafts, and 6 Jotec(r) remained. Mean patency time was 106.7 +/-
      21.9(SD) days and 96.2 +/- 25.9(SD) days for Gore(r) and Jotec(r), respectively.
      Log-rank test showed no significant difference at final follow-up after 6 months.
      Post mortem heparin analysis showed no significant difference in mean activity.
      Conclusion: ; Based on patency data alone, no significant difference between
      these grafts were found. In accordance, heparin activity analysis showed no
      difference between the grafts. The model itself, proved easily implementable, and
      provides many possibilities for future studies, though some adjustments should be
      made to improve survival.

PMID- 30294435
TI  - Complete resection of an anterior mediastinal tumor by total arch replacement and
      pulmonary artery trunk plasty with a pericardial patch: A case report.
AB  - Introduction: Patients with undiagnosed anterior mediastinal tumors commonly
      undergo surgery for diagnosis and treatment. However, determining the optimal
      therapeutic strategy is difficult for tumors with substantial invasion, such as
      lesions touching the aortic arch (AA). Case presentation: A 76-year-old man of
      Asian descent presented to our hospital because chest computed tomography (CT)
      revealed an anterior mediastinal tumor. This tumor surrounded the left subclavian
      vein and touched the AA. We suspected the tumor to be malignant. We therefore
      decided to resect the tumor with preparation for total arch replacement (TAR).
      The operation was performed in three steps. First, we performed a mediastinal
      sternotomy. However, the tumor had invaded the subclavian vein, so we resected
      this vein after adding a transmanubrial approach. However, because of invading
      the AA we needed next step. Second, we shifted the patient to the right lateral
      decubitus position. We performed partial resection of the left upper lobe and
      exfoliated the distal AA. Third, we shifted the patient to the dorsal position
      and implanted an artificial cardiopulmonary device, after which we performed TAR,
      and pulmonary artery (PA) trunk plasty with a pericardial patch. The operation
      was successful, with no major adverse events. Pathologically, the tumor was
      diagnosed as diffuse large B-cell lymphoma. Discussion: If oncologically complete
      resection is preferable for tumors with substantial invasion, complete resection
      should be attempted even if the surgery is difficult. Conclusion: We performed
      complete resection of an anterior mediastinal tumor with TAR and PA trunk plasty
      using a pericardial patch.

PMID- 30294436
TI  - Absence of cognitive symptoms in a 6-year-old male with post-traumatic increased
      intracranial pressure - A case report.
AB  - Introduction: Traumatic Brain Injuries (TBIs) can range from mild to severe, and
      may result in increased intracranial pressure (ICP). Increased ICP causes
      hallmark physical signs, such as diaphoresis, emesis, fixed pupils, and altered
      mental status. Monitoring the patient's score on the Glasgow Coma Scale (GCS) and
      cranial CT scans are routine measures used in clinical practice to monitor the
      development of a TBI. Presentation of the case: A 6-year-old male fell off his
      father's shoulders and subsequently presented to ED for suspected head trauma. He
      was transferred to our Level 1 Trauma Center after a head CT scan demonstrated a
      subdural hematoma. His GCS score remained 15. The next day he began to have
      episodes of apnea and desaturation. Further imaging indicated expansion of the
      hematoma with a 5mm midline shift. He remained consistently alert and a
      neurological exam revealed cranial nerves to be grossly intact. Increased ICP was
      reduced with several days of hypertonic saline treatment without surgical
      intervention. Discussion: TBIs can have long-lasting effects in pediatric
      patients and are typically assessed using both diagnostic imaging and clinical
      judgment. CT scans are used to assess for hematoma development, while loss of
      consciousness (LOC) and altered mental status are standard clinical diagnostic
      indicators of increased ICP. This patient remained alert with a GCS score of 15,
      although he had clinical signs of increased ICP including apnea and bradycardia
      with a midline shift confirmed on imaging. Conclusion: While GCS is an important
      prognostic indicator in TBI, patients should still be monitored to assure
      resolution of all symptoms.

PMID- 30294437
TI  - Neuromuscular electrical stimulation is ineffective for treating quadriceps
      muscle wasting with ruptured aneurysm: A case report.
AB  - Introduction: Neuromuscular electrical stimulation (NMES) is a preventive
      intervention for muscle wasting in patients with aneurysms during the acute
      phase; however, its efficacy still remains unclear. In this case study, we report
      the effects of NMES on quadriceps muscle wasting for a patient with ruptured
      middle cerebral artery aneurysms during the acute phase. Presentation of case: A
      66-year-old woman was admitted because of a ruptured middle cerebral artery
      aneurysm resulting from intracerebral hematoma with subarachnoid hemorrhage. The
      following day, the patient started undergoing 60-120-min NMES treatment for both
      her quadriceps muscles, which was continued for 10 days in 2 weeks. Quadriceps
      muscle thickness as measured by ultrasonography was decreased in both sides (26%
      and 35% for the right and left sides, respectively). The compound muscle action
      potential (CMAP) amplitude in the peroneal nerve was also decreased in both sides
      (73% vs 76%). Discussion: The lack of efficacy of NMES in preventing muscle
      wasting is the decreased CMAP amplitude in this patient, which showed the
      possibility of existence of critical illness polyneuropathy. Conclusion: NMES had
      no effect on quadriceps muscle wasting in a patient with ruptured middle cerebral
      artery aneurysms who had decreased CMAP amplitude in the peroneal nerve during
      the acute phase. NMES is not effective for patients with peripheral nerve
      conduction abnormalities.

PMID- 30294438
TI  - Preliminary radiological result after establishment of hospital-based trauma
      registry in level-1 trauma hospital in developing country setting, prospective
      cohort study.
AB  - Introduction: Injuries are the second most common cause of disability, the fifth
      most common cause of healthy years of life lost per 1000 people and unfortunately
      90% of mortality takes place in low-to middle-income countries. Trauma registries
      guide policymakers and health care providers in decision making in terms of
      resource allocation as well as enhancing trauma care outcomes. Furthermore data
      from these registries inform policy makers to decrease the rate of death and
      disability occurring as a result of injuries. We present our experience in
      setting up an orthopedic trauma registry and the first short term follow-up of
      radiological outcomes. Materials and methodology: Our study is a non-funded, non
      commercial, prospective cohort study that was registered at Research Registry.
      The primary objectives of our study included assessing pattern of injuries in
      patients with upper and lower limb skeletal trauma presenting to our tertiary
      care academic university hospital and their respective outcomes. Data was
      collected by the musculoskeletal service line team members supervised by an
      experienced research associate and trauma consultants. The work has been reported
      in line with the STROCSS criteria. Results: A total of 177 patients were included
      in this analysis, of whom 101 (57.1%) patients had lower limb fractures,
      64(36.1%) patients ad upper limb fractures and 12 (6.8%) patients had both upper
      and lower limbs involved. A total of 189 upper and lower limb fracture cases were
      recorded. 176 patients (93.1%) underwent surgeries and 13(6.9%) were managed
      nonoperatively. Roentgenographic outcomes were assessed using radiological
      criteria for each bone fractured. Conclusion: Establishing a trauma registry
      assists in identification of the pattern of injuries presenting to the hospital
      which helps in priority setting, care management and planning. This continuous
      audit of outcomes in turn, plays a significant role in quality improvement.

PMID- 30294439
TI  - Small bowel obstruction from migrated intragastric balloon.
AB  - Intestinal obstruction resulted from balloon migration is an extremely rare but
      serious late complication of the intragastric balloon (IGB). The aim of this
      study is to report a case of small bowel obstruction occurring in a middle age
      corpulent female following embedding of IGB. A 47-year-old obese female presented
      with abdominal pain, nausea, and vomiting for two days. She had a history of an
      endoscopically placed IGB nine months before presentation. Physical examination
      showed an obese woman with mild distress, and the right upper abdomen was tender.
      The plain abdominal radiograph showed gas shadow in the stomach and the duodenum,
      esophago-gastro-duodenoscopy showed an empty stomach and balloon migration from
      the stomach. Under general anesthesia, laparotomy was performed, a three
      centimeter antimesenteric enterotomy was done and the balloon extracted from the
      proximal jejunum. Intestinal obstruction is an extremely rare complication of
      IGB. It should be managed by laparotomy and extraction of the balloon.

PMID- 30294440
TI  - Rare case of symmetrical peripheral gangrene due to septic shock, disseminated
      intravascular coagulation and inotropic use.
AB  - Introduction: Symmetrical peripheral gangrene (SPG) is a rare syndrome defined by
      the peripheral ischemic lesion of two or more extremities in the absence of major
      vascular obstructive disease. Presentation of case: A 45yo woman, admitted in
      intensive care unit due to urinary septic shock, in need of high doses of amines,
      developed cold extremities with acrocyanosis that rapidly progressed to gangrene.
      Laboratory analysis revealed increased inflammatory parameters, liver shock,
      thrombocytopenia, prolonged coagulation times, increased D-Dimers and isolation
      of Acinetobacter baumanni in urine culture. An intravenous vasodilator was
      initiated with clinical benefits. After improvement and delimitation of the
      lesions, the patient underwent the amputation of the distal phalanges of the 2nd,
      3rd and 4th fingers of the right hand and the toes of both feet.
      Discussion/conclusion: Even though there is no consensus regarding SPG treatment,
      consequences should be mitigated, particularly when vasodilators are used, in
      order to avoid major amputation.

PMID- 30294441
TI  - How to approach Monteggia-like lesions in adults: A review.
AB  - Monteggia-like lesions encompass a wide spectrum of fractures of the forearm and
      elbow associated with dislocations, subluxations and ligamentous lesions. Many
      attempts have been made to classify these injuries, not only to understand their
      pathology but also to develop optimal treatments. Unfortunately, although some of
      these classifications are complete, they are either complex, not immediately
      usable, or not exhaustive. An orthopedic surgeon who aims to rapidly treat this
      kind of injury needs a visual classification, and knowledge of the best surgical
      approach. Monteggia like lesions do not allow for mistakes during surgery, as
      even a minor error could be prove detrimental to performing and completing all
      surgical steps. In this paper, based on our extensive experience in treating
      these rare lesions, we suggest a practical guide to the best surgical approach
      for various types of Monteggia like lesions. Some technical tips and pitfalls are
      also described.

PMID- 30294442
TI  - Gallbladder cancer in Eastern Province of Saudi Arabia: A retrospective cohort
      study.
AB  - Background: There is paucity in the literature regarding gallbladder cancer in
      Saudi Arabia, possibly because it is not among the top 10 cancers diagnosed
      nationwide according to the Saudi Cancer Registry. Moreover, national or regional
      data on gallbladder cancer in Saudi Arabia have not been analyzed. The purpose of
      this study was to describe the presentation, disease stage, histology, and
      survival rates for gallbladder cancer in Saudi patients at a single institution
      between January 1, 2010 and December 31, 2017. Materials and methods: This was a
      retrospective study of 76 patients who presented to our hospital between January
      1, 2010 and December 31, 2017, with established diagnosis of gallbladder
      carcinoma. The diagnosis was made either histopathologically following simple
      laparoscopic cholecystectomy or biopsy from metastatic liver lesion in patients
      with gallbladder mass, or the high suspicion of gallbladder carcinoma based on
      incidental radiological findings. Presentation, disease stage, histology, and
      treatment modalities were analyzed using descriptive statistics and frequency
      distributions. Survival rates were analyzed and presented using Kaplan-Meier
      curves. Results: Based on initial analyses the disease was more frequent among
      women (62.0%) than men (39.0%). Surgical resection was attempted in 40.8%
      patients. The average age at presentation and diagnosis of gallbladder carcinoma
      was 62.4 years. The disease had two peaks, one at 51.0 years and the other
      between 66.0 and 70.0 years. The median survival time for the overall at-risk
      patients was only 1.0 year, while for stage IVB patients was 7.2 months.
      Adenocarcinoma not otherwise specified (NOS) was the most common histopathology
      type (75.0%), with most patients presenting with stage IVB disease (75.0%).
      Gallbladder carcinoma was incidentally detected in 42.1%, including three cases
      (3.9%) diagnosed at our hospital. Conclusions: Gallbladder cancer is a rare type
      of cancer in Saudi Arabia, and most patients are treated surgically, despite
      being mostly diagnosed at the advanced stage of the disease.

PMID- 30294443
TI  - Postoperative complications following tonsil and adenoid removal in Kuwaiti
      children: A retrospective study.
AB  - Background: Adenoidectomy and adenotonsillectomy are two of the most common
      procedures that are performed by otolaryngologists around the world.
      Complications, ranging from major to minor ones, are affected by the preoperative
      symptoms and health status of the patient. We aimed to identify the prevalence of
      major postadenoidectomy and adenotonsillectomy complications, including bleeding,
      and minor complications, including malodor, fever, and snoring. Materials and
      methods: We conducted a retrospective chart review of 825 patients who underwent
      surgery between January 2002 and 30 December 2016 at our institution. Results:
      The bleeding complications prevalence was 4.1% (14/344) among patients with
      adenotonsillectomy and 1.3% (6/480) among those who underwent adenoidectomy.
      Results revealed that tonsil grade 3 patients were at a reduced risk (86% reduced
      risk) of developing bleeding complications, compared to those with tonsil grade 2
      [odds ratio (OR) = 0.141, 95% confidence interval (CI): (0.028, 0.715)]. Grade C
      tympanogram patients had ten times the odds of bleeding complications compared to
      those with tympanogram grade A [OR = 10.6, 95% CI: 0.917, 122.54], a marginally
      significant difference (probability value (PV) = 0.054). Upper respiratory tract
      infections (URTIs) patients had three times the odds of bleeding complications
      compared to those without URTIs [OR = 3.03, 95% CI: (0.979, 9.439)], also a
      marginally significant difference (PV = 0.055). Postoperatively, 71% experienced
      no malodor, 23% had malodor lasting 3-7 days, and 1% had malodor for 7-10 days.
      Our analysis showed that 71% of the patients did not complain of snoring, 25% had
      snoring for 3-7 days, and 2% had snoring for 7-10 days. 80% of the patients did
      not develop fever, 13% had fever for 3-7 days, and no patients experienced fever
      for longer than 7 days. Conclusions: Nearly 4% of the patients developed bleeding
      after adenotonsillectomy and only 2% of the patients had only bleeding after
      adenoidectomy. Conversely, 15-25% of the patients developed minor complications,
      including malodor, snoring, and fever, independent of their preoperative
      symptoms.

PMID- 30294444
TI  - The role of stable isotopes in understanding rainfall interception processes: A
      review.
AB  - The isotopic composition of water transmitted by the canopy as throughfall or
      stemflow reflects a suite of processes modifying rainfall. Factors that affect
      isotopic composition of canopy water include fractionation, exchange between
      liquid and vapor, and selective transmittance of temporally varying rainfall
      along varying canopy flowpaths. Despite frequent attribution of canopy effects on
      isotopic composition of throughfall to evaporative fractionation, data suggest
      exchange and selection are more likely the dominant factors. Temporal variability
      in canopy effects is generally consistent with either exchange or selection, but
      spatial variability is generally more consistent with selection. However, most
      investigations to date have not collected data sufficient to unambiguously
      identify controlling processes. Using isotopic data for improved understanding of
      physical processes and water routing in the canopy requires recognizing how these
      factors and processes lead to patterns of isotopic variability, and then applying
      this understanding towards focused data collection and analysis.

PMID- 30294445
TI  - The in vivo fates of plant viral nanoparticles camouflaged using self-proteins:
      overcoming immune recognition.
AB  - Nanoparticles offer a promising avenue for targeted delivery of therapies. To
      slow clearance, nanoparticles are frequently stealth-coated to prevent
      opsonization and immune recognition. Serum albumin (SA) has been used as a bio
      inspired stealth coating. To develop this shielding strategy for clinical
      applications, it is critical to understand the interactions between the immune
      system and SA-camouflaged nanoparticles. This work investigates the in vivo
      processing of SA-coated nanoparticles using tobacco mosaic virus (TMV) as a model
      system. In comparing four different SA-formulations, the particles with high SA
      coverage conjugated to TMV via a short linker performed the best at preventing
      antibody recognition. Irrelevant of the coating chemistry, all formulations led
      to similar levels of TMV-specific antibodies after repeat administration in mice;
      importantly though, SA-specific antibodies were not detected and the TMV-specific
      antibodies were unable to recognize shielded SA-coated TMV. Upon uptake in
      macrophages, the shielding agent and nanoparticle separate, where TMV trafficked
      to the lysosome and SA appears to recycle. The distinct intracellular fates of
      the TMV carrier and SA shielding agent explain why anti-TMV but not SA-specific
      antibodies are generated. This work characterizes the outcomes of SA-camouflaged
      TMV after immune recognition, and highlights the effectiveness of SA as a
      nanoparticle shielding agent.

PMID- 30294446
TI  - Controlling excimer formation in indolo[3,2,1-jk]carbazole/9H-carbazole based
      host materials for RGB PhOLEDs.
AB  - Three novel materials (5CzICz, Cz2ICz and Cz3ICz), based on the indolo[3,2,1
      jk]carbazole and 9H-carbazole building blocks, with high triplet energies (E T >
      2.80 eV) and good thermal stability (T g > 101  degrees C) were synthesized,
      characterized and applied as host materials in PhOLED devices. In course of the
      preparation of the materials, an improved protocol for the synthesis of the
      indolo[3,2,1-jk]carbazole moiety has been developed. The careful molecular design
      of the title compounds allowed to avoid excimer formation of the indolo[3,2,1
      jk]carbazole subunits in thin films. Therefore, the improved molecular design
      broadened the applicability of indolo[3,2,1-jk]carbazole host materials and
      significantly enhanced the efficiency of PhOLED devices based on these
      derivatives compared to previously reported indolo[3,2,1-jk]carbazole based
      compounds. Accordingly, employing the newly developed materials red (CEmax: 32.7
      cd A-1, PEmax: 31.0 lm W-1, EQEmax: 20.4%), green (CEmax: 81.0 cd A-1, PEmax:
      87.4 lm W-1, EQEmax: 21.5%) and blue (CEmax: 35.5 cd A-1, PEmax: 39.9 lm W-1,
      EQEmax: 18.0%) PhOLED devices with a remarkably low efficiency roll-off at 1000
      cd m-2 (Cz2ICz - red: 5%; green: 0%; blue: 6%) were fabricated.

PMID- 30294447
TI  - Approach to the Synthesis of the C1-C11 and C14-C18 portion of Leucascandrolide
      A.
AB  - An asymmetric synthesis of the C1 to C11 and C14 to C18 fragments of the
      macrocyclic portion of the antibiotic Leucascandrolide A was achieved in 21 total
      steps from an achiral dienoate. The key 4-hydroxy-2,5-pyran portion of the
      natural product was established by oxy-Michael cyclization of a 5,7,9,11-tetraol
      intermediate, which in turn was established by an iterative asymmetric-hydration
      of dienoates. Alternative strategies for establishing the polyol stereochemistry
      were explored.

PMID- 30294448
TI  - Metacognitive therapy versus cognitive-behavioural therapy in adults with
      generalised anxiety disorder.
AB  - Background: Cognitive-behavioural therapy (CBT) is the treatment of choice for
      generalised anxiety disorder (GAD), yielding significant improvements in
      approximately 50% of patients. There is significant room for improvement in the
      outcomes of treatment, especially in recovery. Aims: We aimed to compare
      metacognitive therapy (MCT) with the gold standard treatment, CBT, in patients
      with GAD (clinicaltrials.gov identifier: NCT00426426). Method: A total of 246
      patients with long-term GAD were assessed and 81 were randomised into three
      conditions: CBT (n = 28), MCT (n = 32) and a wait-list control (n = 21).
      Assessments were made at pre-treatment, post-treatment and at 2 year follow-up.
      Results: Both CBT and MCT were effective treatments, but MCT was more effective
      (mean difference 9.762, 95% CI 2.679-16.845, P = 0.004) and led to significantly
      higher recovery rates (65% v. 38%). These differences were maintained at 2 year
      follow-up. Conclusions: MCT seems to produce recovery rates that exceed those of
      CBT. These results demonstrate that the effects of treatment cannot be attributed
      to non-specific therapy factors. Declaration of interest: A.W. wrote the
      treatment protocol in MCT and several books on CBT and MCT, and receives
      royalties from these. T.D.B. wrote the protocol in CBT and has published several
      articles and chapters on CBT and receives royalties from these. All other authors
      declare no competing interests.

PMID- 30294449
TI  - Deaths in custody in the Irish prison service: 5-year retrospective study of drug
      toxicology and unnatural deaths.
AB  - : Mental health and substance misuse disorders are associated with unnatural
      deaths in prisoners. Deaths in Irish prisons between 2009 and 2014 were
      retrospectively analysed using coroner's findings, including post-mortem
      toxicology. There were 69 deaths in custody, 38 of which met inclusion criteria.
      All deaths by overdose (16) were positive for illicit drugs; 53% of deaths (8 of
      15) due to hanging were also positive for illicit drugs, and 29% of deaths (2 of
      7) from other causes were toxicology positive. In conclusion, 26 unnatural deaths
      (68%) were associated with use of illicit drugs, which are a major contributory
      factor to deaths of prisoners. Declaration of interest: None.

PMID- 30294450
TI  - Development and clinimetric assessment of a nurse-administered screening tool for
      movement disorders in psychosis.
AB  - Background: Movement disorders associated with exposure to antipsychotic drugs
      are common and stigmatising but underdiagnosed. Aims: To develop and evaluate a
      new clinical procedure, the ScanMove instrument, for the screening of
      antipsychotic-associated movement disorders for use by mental health nurses.
      Method: Item selection and content validity assessment for the ScanMove
      instrument were conducted by a panel of neurologists, psychiatrists and a mental
      health nurse, who operationalised a 31-item screening procedure. Interrater
      reliability was measured on ratings for 30 patients with psychosis from ten
      mental health nurses evaluating video recordings of the procedure. Criterion and
      concurrent validity were tested comparing the ScanMove instrument-based rating of
      13 mental health nurses for 635 community patients from mental health services
      with diagnostic judgement of a movement disorder neurologist based on the
      ScanMove instrument and a reference procedure comprising a selection of commonly
      used rating scales. Results: Interreliability analysis showed no systematic
      difference between raters in their prediction of any antipsychotic-associated
      movement disorders category. On criterion validity testing, the ScanMove
      instrument showed good sensitivity for parkinsonism (90%) and hyperkinesia (89%),
      but not for akathisia (38%), whereas specificity was low for parkinsonism and
      hyperkinesia, and moderate for akathisia. Conclusions: The ScanMove instrument
      demonstrated good feasibility and interrater reliability, and acceptable
      sensitivity as a mental health nurse-administered screening tool for parkinsonism
      and hyperkinesia. Declaration of interest: None.

PMID- 30294451
TI  - Demographic and clinical predictors of response to internet-enabled cognitive
      behavioural therapy for depression and anxiety.
AB  - Background: Common mental health problems affect a quarter of the population.
      Online cognitive-behavioural therapy (CBT) is increasingly used, but the factors
      modulating response to this treatment modality remain unclear. Aims: This study
      aims to explore the demographic and clinical predictors of response to one-to-one
      CBT delivered via the internet. Method: Real-world clinical outcomes data were
      collected from 2211 NHS England patients completing a course of CBT delivered by
      a trained clinician via the internet. Logistic regression analyses were performed
      using patient and service variables to identify significant predictors of
      response to treatment. Results: Multiple patient variables were significantly
      associated with positive response to treatment including older age, absence of
      long-term physical comorbidities and lower symptom severity at start of
      treatment. Service variables associated with positive response to treatment
      included shorter waiting times for initial assessment and longer treatment
      durations in terms of the number of sessions. Conclusions: Knowledge of which
      patient and service variables are associated with good clinical outcomes can be
      used to develop personalised treatment programmes, as part of a quality
      improvement cycle aiming to drive up standards in mental healthcare. This study
      exemplifies translational research put into practice and deployed at scale in the
      National Health Service, demonstrating the value of technology-enabled treatment
      delivery not only in facilitating access to care, but in enabling accelerated
      data capture for clinical research purposes. Declaration of interest: A.C., S.B.,
      V.T., K.I., S.F., A.R., A.H. and A.D.B. are employees or board members of the
      sponsor. S.R.C. consults for Cambridge Cognition and Shire. Keywords: Anxiety
      disorders; cognitive behavioural therapies; depressive disorders; individual
      psychotherapy.

PMID- 30294453
TI  - WHEN SCIENTIFIC PARADIGMS LEAD TO TUNNEL VISION: LESSONS FROM THE STUDY OF FEAR.
AB  - For the past 30 years, research on the amygdala has largely focused on the
      genesis of defensive behaviors as its main function. This focus originated from
      early lesion studies and was supported by extensive anatomical, physiological,
      and pharmacological data. Here we argue that while much data is consistent with
      the fear model of amygdala function, it has never been directly tested, in part
      due to overreliance on the fear conditioning task. In support of the fear model,
      amygdala neurons appear to signal threats and/or stimuli predictive of threats.
      However, recent studies in a natural threat setting show that amygdala activity
      does not correlate with threats, but simply with the movement of the rat,
      independent of valence. This was true for both natural threats as well as
      conditioned stimuli; indeed there was no evidence of threat signaling in amygdala
      neurons. Similar findings are emerging for prefrontal neurons that modulate the
      amygdala. These recent developments lead us to propose a new conceptualization of
      amygdala function whereby the amygdala inhibits behavioral engagement. Moreover,
      we propose that the goal of understanding the amygdala will be best served by
      shifting away from fear conditioning toward naturalistic approach and avoidance
      paradigms that involve decision making and a larger repertoire of spontaneous and
      learned behaviors, all the while keeping an open mind.

PMID- 30294454
TI  - Malignant Pleural Mesothelioma presenting with Cardiac Tamponade- A Rare Case
      report and Review of the literature.
AB  - Mesothelioma is a rare tumor of the pleura, peritoneum, pericardium or tunica
      vaginalis. About 2,500 cases are diagnosed annually in the United States.
      Mesothelioma often presents with pleuritic chest pain and dyspnea related to
      local invasion; distal metastasis and lymphadenopathy at the time of diagnosis is
      rare. Pericardial involvement in mesothelioma is related to direct invasion of
      the tumor. We here present a 71 year-old-male who presented with pleuritic chest
      pain and dyspnea, noted to have diffuse ST-segment elevation in EKG and cardiac
      tamponade physiology on 2D echocardiogram in who imaging subsequently revealed
      left upper lung mesothelioma. A pericardial window was created following which
      tamponade resolved. The pericardial biopsy did not show any mesothelioma cells or
      fibrous plaques. Computer tomography revealed regional lymphadenopathy in the
      chest. Disrupted cardiac lymphatic flow due to tumor mesothelioma induced
      lymphadenopathy is likely cause of the cardiac tamponade in this patient. This is
      the second ever reported case of pleural mesothelioma without a direct
      pericardial invasion that presented with cardiac tamponade.

PMID- 30294455
TI  - Using strategic information for action: lessons from the HIV/AIDS response in
      Vietnam.

PMID- 30294452
TI  - Common oscillatory mechanisms across multiple memory systems.
AB  - The cortex, hippocampus, and striatum support dissociable forms of memory. While
      each of these regions contains specialized circuitry supporting their respective
      functions, all structure their activities across time with delta, theta, and
      gamma rhythms. We review how these oscillations are generated and how they
      coordinate distinct memory systems during encoding, consolidation, and retrieval.
      First, gamma oscillations occur in all regions and coordinate local spiking,
      compressing it into short population bursts. Second, gamma oscillations are
      modulated by delta and theta oscillations. Third, oscillatory dynamics in these
      memory systems can operate in either a 'slow' or 'fast' mode. The slow mode
      happens during slow-wave sleep (SWS) and is characterized by large irregular
      activity in the hippocampus and delta oscillations in cortical and striatal
      circuits. The fast mode occurs during active waking and REM and is characterized
      by theta oscillations in the hippocampus and its targets, along with gamma
      oscillations in the rest of cortex. In waking, the fast mode is associated with
      the efficacious encoding and retrieval of declarative and procedural memories.
      Theta and gamma oscillations have the similar relationships with encoding and
      retrieval across multiple forms of memory and brain regions, despite regional
      differences in microcircuitry and information content. Differences in the
      oscillatory coordination of memory systems during sleep might explain why the
      consolidation of some forms of memory is sensitive to SWS, while others depend on
      REM. In particular, theta oscillations appear to support the consolidation of
      certain types of procedural memories during REM, while delta oscillations during
      SWS seem to promote declarative and procedural memories.

PMID- 30294456
TI  - Data for decision making: using a dashboard to strengthen routine immunisation in
      Nigeria.
AB  - Availability of reliable data has for a long time been a challenge for health
      programmes in Nigeria. Routine immunisation (RI) data have always been
      characterised by conflicting coverage figures for the same vaccine across
      different routine data reporting platforms. Following the adoption of District
      Health Information System version 2 (DHIS2) as a national electronic data
      management platform, the DHIS2 RI Dashboard Project was initiated to address the
      absence of some RI-specific indicators on DHIS2. The project was also intended to
      improve visibility and monitoring of RI indicators as well as strengthen the
      broader national health management information system by promoting the use of
      routine data for decision making at all governance levels. This paper documents
      the process, challenges and lessons learnt in implementing the project in
      Nigeria. A multistakeholder technical working group developed an implementation
      framework with clear preimplementation; implementation and postimplementation
      activities. Beginning with a pilot in Kano state in 2014, the project has been
      scaled up countrywide. Nearly 34 000 health workers at all administrative levels
      were trained on RI data tools and DHIS2 use. The project contributed to the
      improvement in completeness of reports on DHIS2 from 53 % in first quarter 2014
      to 81 % in second quarter 2017. The project faced challenges relating to primary
      healthcare governance structures at the subnational level, infrastructure and
      human resource capacity. Our experience highlights the need for early and
      sustained advocacy to stakeholders in a decentralised health system to promote
      ownership and sustainability of a centrally coordinated systems strengthening
      initiative.

PMID- 30294457
TI  - Population surveillance of cardiovascular diseases in low-income to middle-income
      countries should leverage existing international collaborations.

PMID- 30294458
TI  - Plain packaging of tobacco products: the logical next step for tobacco control
      policy in India.
AB  - India implemented larger 85% pictorial health warnings on all tobacco products
      from 1 April 2016. However, to remove the last bit of glamour and attraction from
      the tobacco packs, it must now embrace plain packaging. Plain packaging prevents
      tobacco packs from carrying the tobacco industry brand imagery as mobile
      billboards. Postimplementation of larger 85% pictorial health warnings on all
      tobacco products, this analysis was undertaken to assess the feasibility of plain
      packaging as the next logical tobacco control policy measure in India. As part of
      this analysis, the research team reviewed the available literature on legal and
      policy challenges to plain packaging as a tobacco control policy initiative for
      India. Literature from 2010 to 2016 in English language was reviewed, which
      reveals that, India has taken several preparatory steps implemented by other
      countries like Australia and the UK that have introduced plain packaging, for
      example, stronger smoke-free laws, ban on tobacco advertising, promotion and
      sponsorship, increase in taxes and a report from civil society task force on
      plain packaging. The trade and investment agreements signed by India are also
      within the international trade norms relating to public health. A Private
      Member's Bill on plain packaging is also pending in the Parliament of India.
      Other potential challenges against such policy decision, for example, freedom of
      trade, right to property, violation of competition law and other laws including
      consumer protection laws, were found unsubstantiated by the research team. Plain
      packaging is the next logical step for tobacco control policy in India.

PMID- 30294459
TI  - Time to include burden of surgical injuries after disasters in the Global Surgery
      agenda? An assessment of DALYs and averted burden by surgery after the 2008
      Wenchuan earthquake.
AB  - Unlike other disasters, injury rates after earthquakes are still on the rise at a
      global scale. With an estimated one million people injured by earthquakes in the
      last decade, the burden of injury is considerable. Importantly, the surgical
      procedures carried out by healthcare facilities are capable to avert part of this
      burden. Yet both burdens remain unquantified using understandable metrics. We
      explored in this analysis a method to calculate them using disability-adjusted
      life years (DALYs), an internationally accepted measure expressing years of
      healthy life lost due to a health condition. We used data from a large
      standardised hospital database of earthquake-related injuries with complete
      information on International Classification of Diseases for injury and surgical
      procedures, sex and age information. DALYs and averted DALYs were calculated by
      injury types and per patient using disability weights available in the literature
      and expert opinion. We also suggested how DALYs might be further converted into
      an economic measure using approaches in the published literature. We estimated 10
      397 DALYs as the earthquake surgical-injury burden produced in 1861 hospitalised
      patients treated in a single hospital (on average, 5.6 DALYs per patient). Our
      study also assessed that 4379 DALYs, or 2.4 DALYs per patient, were averted by
      surgery (42%). In economic terms, DALY losses amounted to US$36.1 million, from
      which US$15.2 million were averted by surgery in our case study. We urge to
      systematically estimate these impacts through improvements in the routine
      reporting of injury diagnoses and surgical procedures by health systems,
      potentially improving prevention policies and resource allocation to healthcare
      facilities.

PMID- 30294461
TI  - Performance-based financing versus improving salary payments to workers: insights
      from the Democratic Republic of Congo.

PMID- 30294460
TI  - Health system governance following devolution: comparing experiences of
      decentralisation in Kenya and Indonesia.
AB  - Introduction: Devolution reforms in Indonesia and Kenya have brought extensive
      changes to governance structures and mechanisms for financing and delivering
      healthcare. Community health approaches can contribute towards attaining many of
      devolution's objectives, including community participation, responsiveness,
      accountability and improved equity. We set out to examine governance in two
      countries at different stages in the devolution journey: Indonesia at 15 years
      postdevolution and Kenya at 3 years. Methods: We collected qualitative data
      across multiple levels of the health system in one district in Indonesia and ten
      counties in Kenya, through 80 interviews and six focus group discussions (FGD) in
      Indonesia and 269 interviews and 14 FGDs in Kenya. Qualitative data were
      digitally recorded, transcribed and coded before thematic framework analysis.
      Common themes between contexts were identified inductively and deductively, and
      similarities and differences critically analysed during an inter-country analysis
      workshop. Results: Following devolution both Indonesia and Kenya experienced
      similar challenges ensuring good governance for health. Devolution reforms
      transformed power relationships, increasing responsibilities at subnational
      levels and introducing opportunities for citizen participation. In both contexts,
      the impact of these mechanisms has been undermined by insufficiently clear
      guidance; failure to address pre-existing negative contextual norms and practices
      varied decision-maker values, limited priority-setting capacity and limited
      genuine community accountability. As a consequence, priorities in both contexts
      are too often placed on curative rather than preventive health services.
      Conclusion: We recommend consideration of increased intersectoral actions that
      address social determinants of health, challenge negative norms and practices and
      place emphasis on community-based primary health services.

PMID- 30294462
TI  - Integrated health system strengthening can generate rapid population impacts that
      can be replicated: lessons from Rwanda to Madagascar.

PMID- 30294463
TI  - Lies, damned lies and epidemiology: why global health needs good epidemiological
      practice guidelines.

PMID- 30294464
TI  - Towards constructive rethinking of PBF: perspectives of implementers in sub
      Saharan Africa.

PMID- 30294465
TI  - A planetary vision for one health.

PMID- 30294466
TI  - Developing and Piloting a Community Scientist Academy to Engage Communities and
      Patients in Research.
AB  - Introduction: Effective translational research requires engagement and
      collaboration between communities, researchers, and practitioners. We describe a
      community scientist academy (CSA) developed at the suggestion of our CTSA's
      community advisory board to engage and capacitate community members by 1)
      increasing community members' and patients' understanding about the research
      process and 2) increasing their access to opportunities to influence and
      participate in research. A joint CTSA/community planning committee developed this
      8-hour workshop including sessions on: 1) research definitions and processes; 2)
      study design; 3) study implementation; and 4) ways to get involved in research.
      The workshop format includes interactive exercises, content slides and videos,
      and researcher and community presenters. Methods: Community-based information
      sessions allowed assessment of community interest before piloting. Two pilots of
      the CSA were conducted with community members and patients. Participant data and
      a pre/post knowledge and feedback survey provides evaluation data. Results: The
      pilot included 24 diverse participants, over half of whom had not previously
      participated in research. Evaluation data suggest knowledge gains. Post- CSA, one
      third have reviewed CTSA pilot grants and over 80% want to attend further
      training. Conclusions: The CSA can demystify the research process for those
      underrepresented in research and facilitate their engagement and influence within
      CTSAs.

PMID- 30294467
TI  - Guidelines for evaluation and management of cerebral collateral circulation in
      ischaemic stroke 2017.
AB  - Collateral circulation plays a vital role in sustaining blood flow to the
      ischaemic areas in acute, subacute or chronic phases after an ischaemic stroke or
      transient ischaemic attack. Good collateral circulation has shown protective
      effects towards a favourable functional outcome and a lower risk of recurrence in
      stroke attributed to different aetiologies or undergoing medical or endovascular
      treatment. Over the past decade, the importance of collateral circulation has
      attracted more attention and is becoming a hot spot for research. However, the
      diversity in imaging methods and criteria to evaluate collateral circulation has
      hindered comparisons of findings from different cohorts and further studies in
      exploring the clinical relevance of collateral circulation and possible methods
      to enhance collateral flow. The statement is aimed to update currently available
      evidence and provide evidence-based recommendations regarding grading methods for
      collateral circulation, its significance in patients with stroke and methods
      under investigation to improve collateral flow.

PMID- 30294468
TI  - Contribution of diffusion, perfusion and functional MRI to the disconnection
      hypothesis in subcortical vascular cognitive impairment.
AB  - Vascular cognitive impairment (VCI) describes all forms of cognitive impairment
      caused by any type of cerebrovascular disease. Early identification of VCI is
      quite difficult due to the lack of both sensitive and specific biomarkers.
      Extensive damage to the white matter tracts, which connect the cortical and
      subcortical regions, has been shown in subcortical VCI (SVCI), the most common
      subtype of VCI that is caused by small vessel disease. Two specific MRI
      sequences, including diffusion tensor imaging (DTI) and functional MRI (fMRI),
      have emerged as useful tools for identifying subtle white matter changes and the
      intrinsic connectivity between distinct cortical regions. This review describes
      the advantages of these two modalities in SVCI research and the current DTI and
      fMRI findings on SVCI. Using DTI technique, a variety of studies found that white
      matter microstructural damages in the anterior and superior areas are more
      specific to SVCI. Similarly, functional brain abnormalities detected by fMRI have
      also been mainly shown in anterior brain areas in SVCI. The characteristic
      distribution of brain abnormalities in SVCI interrupts the prefrontal-subcortical
      loop that results in cognitive impairments in particular domains, which further
      confirms the 'disconnection syndrome' hypothesis. In addition, another MRI
      technique, arterial spin labelling (ASL), has been used to describe the
      disconnection patterns in a variety of conditions by measuring cerebral blood
      flow. The role of the ASL technique in SVCI research is also assessed. Finally,
      the review proposes the application of multimodality fusion in the investigation
      of SVCI pathogenesis.

PMID- 30294469
TI  - Stenting for intracranial stenosis: potential future for the prevention of
      disabling or fatal stroke.
AB  - Intracranial stenosis is a common cause of ischaemic strokes, in particular, in
      the Asian, African and Hispanic populations. The randomised multicentre study
      Stenting and Aggressive Medical Management for the Prevention of Recurrent stroke
      in Intracranial Stenosis (SAMMPRIS) showed 14.7% risk of stroke or death in the
      stenting group versus 5.8% in the medical group at 30 days, and 23% in the
      stenting group versus 15% in the medical group at a median follow-up of 32.4
      months. The results demonstrated superiority of medical management over stenting
      and have almost put the intracranial stenting to rest in recent years. Of note,
      16 patients (7.1%) in the stenting group had disabling or fatal stroke within 30
      days mostly due to periprocedural complications as compared with 4 patients
      (1.8%) in the medical group. In contrast, 5 patients (2.2%) in the stenting group
      and 14 patients (6.2%) in the medical group had a disabling or fatal stroke
      beyond 30 days, indicating significant benefit of stenting if periprocedural
      complications can be reduced. Recently, the results of the Chinese Angioplasty
      and Stenting for Symptomatic Intracranial Severe Stenosis trial and the Wingspan
      Stent System Post Market Surveillance Study (WEAVE trial) showed 2%-2.7%
      periprocedural complications. It is time to evaluate the role of intracranial
      stenting for the prevention of disabling or fatal stroke.

PMID- 30294470
TI  - Registry report on prediction by Pocock cardiovascular score of cerebral
      microemboli acutely following carotid endarterectomy.
AB  - Background: Cerebral microemboli may lead to ischaemic neurological complications
      after carotid endarterectomy (CEA). The association between classical
      cardiovascular risk factors and acute cerebral microemboli following carotid
      surgery has not been studied. The aim of this study was to explore whether an
      established cardiovascular risk score (Pocock score) predicts the presence of
      cerebral microemboli acutely after CEA. Subjects and methods: Pocock scores were
      assessed for the 670 patients from the Carotid Surgery Registry (age 71+/-1 (SEM)
      years, 474 (71%) male, 652 (97%) Caucasian) managed from January 2002 to December
      2012 in the Regional Vascular Centre at University Hospitals Coventry and
      Warwickshire NHS Trust, which serves a population of 950 000. CEA was undertaken
      in 474 (71%) patients for symptomatic carotid stenosis and in 196 (25%)
      asymptomatic patients during the same period. 74% of patients were hypertensive,
      71% were smokers and 49% had hypercholesterolaemia. Results: A high Pocock score
      (>=2.3%) was significantly associated with evidence of cerebral microemboli
      acutely following CEA (P=0.039, Mann-Whitney (MW) test). A Pocock score (>=2.3%)
      did not predict patients who required additional antiplatelet therapy
      (microemboli signal (MES) rate >50 hour-1: P=0.164, MW test). Receiver operating
      characteristic analysis also showed that the Pocock score predicts acute
      postoperative microemboli (area under the curve (AUC) 0.546, 95% CI 0.502 to
      0.590, P=0.039) but not a high rate of postoperative microemboli (MES >50 hour-1:
      AUC 0.546, 95% CI 0.482 to 0.610, P=0.164). A Pocock score >=2.3% showed a
      sensitivity of 74% for the presence of acute postoperative cerebral microemboli.
      A Pocock score >=2.3% also showed a sensitivity of 77% and a negative predictive
      value of 90% for patients who developed a high microembolic rate >50 hour-1 after
      carotid surgery. Conclusion: These findings demonstrate that the Pocock score
      could be used as a clinical tool to identify patients at high risk of developing
      acute postoperative microemboli.

PMID- 30294471
TI  - Post-stroke mRNA expression profile of MMPs: effect of genetic deletion of MMP
      12.
AB  - Background and purpose: Recent reports from our laboratory demonstrated the post
      ischaemic expression profile of various matrix metalloproteinases (MMPs) in rats
      and the detrimental role of MMP-12 in post-stroke brain damage. We hypothesise
      that the post-stroke dysregulation of MMPs is similar across species and that
      genetic deletion of MMP-12 would not affect the post-stroke expression of other
      MMPs. We tested our hypothesis by determining the pre-ischaemic and post
      ischaemic expression profile of MMPs in wild-type and MMP-12 knockout mice.
      Methods: Focal cerebral ischaemia was induced in wild-type and MMP-12 knockout
      mice by middle cerebral artery occlusion procedure by insertion of a monofilament
      suture. One hour after ischaemia, reperfusion was initiated by removing the
      monofilament. One day after reperfusion, ischaemic brain tissues from various
      groups of mice were collected, and total RNA was isolated and subjected to cDNA
      synthesis followed by PCR analysis. Results: Although the post-stroke expression
      profile of MMPs in the ischaemic brain of mice is different from rats, there is a
      clear species similarity in the expression of MMP-12, which was found to be
      predominantly upregulated in both species. Further, the post-stroke induction or
      inhibition of various MMPs in MMP-12 knockout mice is different from their
      respective expression profile in wild-type mice. Moreover, the brain mRNA
      expression profile of various MMPs in MMP-12 knockout mice under normal
      conditions is also different to their expression in wild-type mice. Conclusions:
      In the ischaemic brain, MMP-12 upregulates several fold higher than any other
      MMP. Mice derived with the genetic deletion of MMP-12 are constitutive and have
      altered MMP expression profile both under normal and ischaemic conditions.

PMID- 30294472
TI  - Association between admission haematocrit and mortality among men with acute
      ischaemic stroke.
AB  - Objective: Anaemia is associated with higher mortality among patients with non
      stroke cardiovascular conditions; less is known regarding the relationship
      between anaemia and mortality among patients with acute ischaemic stroke.
      Methods: Medical records were abstracted for n=3965 veterans from 131 Veterans
      Health Administration facilities who were admitted with ischaemic stroke in
      fiscal year 2007. Haematocrit values within 24 hours of admission were classified
      as <=27%, 28%-32%, 33%-37%, 38%-42%, 43%-47% or >=48%. Multivariate logistic
      regression was used to examine the relationship between anaemia and in-hospital,
      30-day, 6-month and 1-year mortality, adjusting for age, medical comorbidities,
      modified Acute Physiology and Chronic Health Evaluation-III and stroke severity.
      Impact factors were calculated to standardise comparisons between haematocrit
      tier and other covariates. Results: Among n=3750 patients included in the
      analysis, the haematocrit values were <=27% in 2.1% (n=78), 28%-32% in 6.2%
      (n=234), 33%-37% in 17.9% (n=670), 38%-42% in 36.4% (n=1366), 43%-47% in 28.2%
      (n=1059) and >=48% in 9.1% (n=343). Patients with haematocrit <=27%, compared
      with patients in the 38%-42% range, were more likely to have died across all
      follow-up intervals, with statistically significant adjusted ORs (aORs) ranging
      from 2.5 to 3.5. Patients with polycythaemia (ie, haematocrit >=48%) were at
      increased risk of in-hospital mortality (aOR=2.9; 95% CI 1.4 to 6.0), compared
      with patients with mid-range admission haematocrits. Pronounced differences
      between patients receiving and not receiving blood transfusion limited our
      ability to perform a propensity analysis. Impact factors in the 1-year mortality
      model were 0.46 (severe anaemia), 0.06 (cancer) and 0.018 (heart disease).
      Conclusions: Anaemia is independently associated with an increased risk of death
      throughout the first year post stroke; high haematocrit is associated with early
      poststroke mortality. Severe anaemia is associated with 1-year mortality to a
      greater degree than cancer or heart disease. These data cannot address the
      question of whether interventions targeting anaemia might improve patient
      outcomes.

PMID- 30294473
TI  - Procedural complexity independent of P2Y12 reaction unit (PRU) values is
      associated with acute in situ thrombosis in Pipeline flow diversion of cerebral
      aneurysms.
AB  - Background: Acute in situ thrombosis is an ischaemic phenomenon during Pipeline
      embolisation device (PED) procedures with potentially high morbidity and
      mortality. There is controversy regarding the role of platelet function testing
      with P2Y12 assay as a predictor of intraprocedural thromboembolic events. There
      is limited knowledge on whether procedural complexity influences these events.
      Methods: Data were collected retrospectively on 742 consecutive PED cases at a
      single institution. Patients with intraprocedural acute thrombosis were compared
      with patients without these events. Results: A cohort of 37 PED cases with acute
      in situ thrombosis (mean age 53.8 years, mean aneurysm size 8.4 mm) was matched
      with a cohort of 705 PED cases without intraprocedural thromboembolic events
      (mean age 56.4 years, mean aneurysm size 6.9 mm). All patients with in situ
      thrombosis received intra-arterial and/or intravenous abciximab. The two groups
      were evenly matched in patient demographics, previous treatment/subarachnoid
      hemorrhage (SAH) and aneurysm location. There was no statistical difference in
      postprocedural P2Y12 reaction unit (PRU) values between the two groups, with a
      mean of 156 in the in situ thrombosis group vs 148 in the control group
      (p=0.5894). Presence of cervical carotid tortuosity, high cavernous internal
      carotid artery grade, need for multiple PED and vasospasm were not significantly
      different between the two groups. The in situ thrombosis group had statistically
      significant longer fluoroscopy time (60.4 vs 38.4 min, p<0.0001), higher
      radiation exposure (3476 vs 2160 mGy, p<0.0001), higher rates of adjunctive
      coiling (24.3% vs 8.37%, p=0.0010) and higher utilisation of balloon angioplasty
      (37.8% vs 12.2%, p<0.0001). Clinically, the in situ thrombosis cohort had higher
      incidence of major and minor stroke, intracerebral haemorrhage and length of
      stay. Conclusions: Predictors of procedural complexity (higher radiation
      exposure, longer fluoroscopy time, adjunctive coiling and need for balloon
      angioplasty) are associated with acute thrombotic events during PED placement,
      independent of PRU values.

PMID- 30294475
TI  - PED Flex with Shield Technology: a feasible alternative for fusiform MCA
      aneurysms.

PMID- 30294476
TI  - Correction: Ginkgo biloba extract improved cognitive and neurological functions
      of acute ischaemic stroke: a randomised controlled trial.
AB  - [This corrects the article DOI: 10.1136/svn-2017-000104.].

PMID- 30294474
TI  - Stenting for symptomatic intracranial arterial stenosis in China: 1-year outcome
      of a multicentre registry study.
AB  - Background and purpose: A multicentre prospective registry study of individually
      tailored stenting for a patient with symptomatic intracranial atherosclerotic
      stenosis (ICAS) combined with poor collaterals in China showed that the short
      term safety and efficacy of stenting was acceptable. However, it remained
      uncertain whether the low event rate could be of a long term. We reported the 1
      year outcome of this registry study to evaluate the long-term efficacy of
      individually tailored stenting for patients with severe symptomatic ICAS combined
      with poor collaterals. Methods: Patients with symptomatic ICAS caused by 70%-99%
      stenosis located at the intracranial internal carotid, middle cerebral,
      intracranial vertebral or basilar arteries combined with poor collaterals were
      enrolled. Balloon-mounted stent or balloon plus self-expanding stent were
      selected based on the ease of vascular access and lesion morphology determined by
      the operators. The primary outcome was the rate of 30-day stroke, transient
      ischaemic attack and death, and 12-month ischaemic stroke within the same
      vascular territory, haemorrhagic stroke and vascular death after stenting.
      Results: From September 2013 to January 2015, 300 patients (ages 58.3+/-9.78
      years) were recruited. Among them, 159 patients were treated with balloon-mounted
      stent and 141 with balloon plus self-expanding stent. During the 1-year follow
      up, 25 patients had a primary end point event. The probability of primary outcome
      at 1 year was 8.1% (95% CI 5.3% to 11.7%). In 76 patients with digital
      subtraction angiography follow-up, 27.6% (21/76) had re-stenosis >=50% and 18.4%
      (14/76) had re-stenosis >=70%. No baseline characteristic was associated with the
      primary outcome. Conclusion: The event rate remains low over 1 year of
      individually tailored stenting for patients with severe symptomatic ICAS combined
      with poor collaterals. Further randomised trial of comparing individually
      tailored stenting with best medical therapy is needed. Trial registration number:
      NCT01968122; Results.

PMID- 30294477
TI  - New Report of Three Unrecorded Species in Trichoderma harzianum Species Complex
      in Korea.
AB  - The genus Trichoderma (Hypocreaceae, Ascomycota) consists of globally distributed
      fungi. Among them, T. harzianum, one of the most commonly collected Trichoderma
      species, had been known as a polyphyletic or aggregate species. However, a total
      of 19 species were determined from the polyphyletic groups of T. harzianum. Thus,
      we explored Korean "T. harzianum" specimens that were collected in 2013-2014.
      These specimens were re-examined based on a recent study with translate
      elongation factor 1-alpha (EF1alpha) sequences to reveal cryptic Trichoderma
      species in Korea. As a result, four different species, T. afroharzianum, T.
      atrobruneum, T. pyramidale, and T. harzianum, were identified. Except T.
      harzianum, the other three species have not been reported in Korea. In this work,
      we describe these species and provide figures.

PMID- 30294478
TI  - New Species and New Record of Genus Chrysothrix (Chrysotrichaceae, Arthoniales)
      from South Korea and Chile.
AB  - The genus Chrysothrix is very common around the world and easy to be recognized
      by its bright yellowish granular thallus. In this study, investigations of lichen
      mycota in South Korea and Chile from 2010 to 2017 have been done, and some
      Chrysothrix specimens were collected, based on the morphological and chemical
      study on these specimens, five species were confirmed in this study, including
      one new species from Chile, Chrysothrix chilensis D. Liu & J.-S Hur, and one new
      record from South Korea, C. xanthina (Vain.) Kalb. Meanwhile, detail description
      and illustration for each species were present in this study.

PMID- 30294479
TI  - Taxonomy of the Golovinomyces cynoglossi Complex (Erysiphales, Ascomycota)
      Disentangled by Phylogenetic Analyses and Reassessments of Morphological Traits.
AB  - The name Golovinomyces cynoglossi s. lat. is traditionally applied to a complex
      of morphologically similar powdery mildews on hosts of the plant family
      Boraginaceae. The current species-level taxonomy within this complex is ambiguous
      due to the lack of phylogenetic examinations. The present study applied
      phylogenetic methods to clarify the taxonomy of G. cynoglossi s. lat.
      Phylogenetic analysis of rDNA ITS sequences retrieved from Asian, European and
      North American specimens revealed that G. cynoglossi s. lat. collections from
      different hosts involved several species in five clearly separated lineages.
      Clade I consists primarily of Golovinomyces cynoglossi s. str. on Cynoglossum.
      Clade III consists of Golovinomyces sequences retrieved from the host genera
      Symphytum and Pulmonaria. The taxa within clade III are now assigned to G.
      asperifoliorum comb. nov. Clade V encompasses G. cynoglossi s. lat. on the host
      genera Bothriospermum, Buglossoides, Echium, Myosotis, and Trigonotis. The taxa
      within clade V are now assigned to G. asperifolii comb. nov. The species
      concerned in this study were lecto- and epitypified to stabilize their
      nomenclature.

PMID- 30294481
TI  - Diversity and Ecology of Myxomycetes from Kutahya and Konya (Turkey) with Four
      New Records.
AB  - In this study, we examined myxomycetes that developed in moist chamber cultures
      of substrata material collected from Kutahya and Konya provinces in Turkey. We
      collected bark samples from living trees, plant litter from the ground, standing
      dead wood or stumps, and downed and decayed wood or bark and placed them in the
      moist chamber cultures. We identified 36 species belonging to 12 genera of
      myxomycetes. The species determined are listed, and four new records, Didymium
      balearicum Ing, Macbrideola oblonga Pando & Lado, Paradiacheopsis erythropodia
      (Ing) Nann-Bremek. and Perichaena pedata (Lister & G. Lister) G. Lister, are
      added to the mycoflora of Turkey.

PMID- 30294480
TI  - Isolation and Characterization of Two Rare Mucoralean Species with Specific
      Habitats.
AB  - The order Mucorales, the largest in number of species within the Mucoromycotina,
      comprises typically fast-growing saprotrophic fungi. During a study of the fungal
      diversity of undiscovered taxa in Korea, two novel mucoralean strains, CNUFC-GWD3
      9 and CNUFC-EGF1-4, were isolated from specific habitats including freshwater and
      fecal samples, respectively. On the basis of their morphological characteristics
      and sequence analyses of internal transcribed spacer and large subunit ribosomal
      DNA, the CNUFC-GWD3-9 and CNUFC-EGF1-4 isolates were confirmed to be Gilbertella
      persicaria and Pilobolus crystallinus, respectively. It is ecologically,
      pathologically, and mycologically significant to find such rare zygomycetous
      fungi in such specific habitats.

PMID- 30294483
TI  - LAMMER Kinase Lkh1 Is an Upstream Regulator of Prk1-Mediated Non-Sexual
      Flocculation in Fission Yeast.
AB  - The cation-dependent galactose-specific flocculation activity of the
      Schizosaccharomyces pombe null mutant of lkh1 +, the gene encoding LAMMER kinase
      homolog, has previously been reported by our group. Here, we show that disruption
      of prk1 +, another flocculation associated regulatory kinase encoding gene, also
      resulted in cation-dependent galactose-specific flocculation. Deletion of prk1
      increased the flocculation phenotype of the lkh1 + null mutant and its
      overexpression reversed the flocculation of cells caused by lkh1 deletion.
      Transcript levels of prk1 + were also decreased by lkh1 + deletion. Cumulatively,
      these results indicate that Lkh1 is one of the negative regulators acting
      upstream of Prk1, regulating non-sexual flocculation in fission yeast.

PMID- 30294484
TI  - The Major Postharvest Disease of Onion and Its Control with Thymol Fumigation
      During Low-Temperature Storage.
AB  - Onion (Allium cepa L.) is one of the major vegetable crops in Korea that are
      damaged and lost by pathogenic fungal infection during storage due to a lack of
      proper storage conditions. The aim of this study was to determine an appropriate
      control measure using thymol to increase the shelf life of onions. To control
      fungal infections that occur during low-temperature storage, it is necessary to
      identify the predominant fungal pathogens that appear in low-temperature storage
      houses. Botrytis aclada was found to be the most predominant fungal pathogen
      during low-temperature storage. The antifungal activity of the plant essential
      oil thymol was tested and compared to that of the existing sulfur treatments. B.
      aclada growth was significantly inhibited up to 16 weeks with spray treatments
      using a thymol solution. To identify an appropriate method for treating onions in
      a low-temperature storage house, thymol was delivered by two fumigation treatment
      methods, either by heating it in the granule form or as a solution at low
      temperature storage conditions (in vivo). We confirmed that the disease severity
      was reduced up to 96% by fumigating thymol solution compared to the untreated
      control. The efficacy of the fumigation of thymol solution was validated by
      testing onions in a low-temperature storage house in Muan, Jeollanam-do. Based on
      these results, the present study suggests that fumigation of the thymol solution
      as a natural preservative and fungicide can be used as an eco-friendly substitute
      for existing methods to control postharvest disease in long-term storage crops on
      a commercial scale.

PMID- 30294482
TI  - Influence of Temperature on the Bacterial Community in Substrate and
      Extracellular Enzyme Activity of Auricularia cornea.
AB  - Temperature is an important environmental factor that can greatly influence the
      cultivation of Auricularia cornea. In this study, lignin peroxidase, laccase,
      manganese peroxidase, and cellulose in A. cornea fruiting bodies were tested
      under five different temperatures (20  degrees C, 25  degrees C, 30  degrees C,
      35  degrees C, and 40  degrees C) in three different culture periods (10 days, 20
      days and 30 days). In addition, the V4 region of bacterial 16S rRNA genes in the
      substrate of A. cornea cultivated for 30 days at different temperatures were
      sequenced using next-generation sequencing technology to explore the structure
      and diversity of bacterial communities in the substrate. Temperature and culture
      days had a significant effect on the activities of the four enzymes, and changes
      in activity were not synchronized with changes in temperature and culture days.
      Overall, we obtained 487,694 sequences from 15 samples and assigned them to 16
      bacterial phyla. Bacterial community composition and structure in the substrate
      changed when the temperature was above 35  degrees C. The relative abundances of
      some bacteria were significantly affected by temperature. A total of 35 genera at
      five temperatures in the substrate were correlated, and 41 functional pathways
      were predicted in the study. Bacterial genes associated with the membrane
      transport pathway had the highest average abundance (16.16%), and this increased
      at 35  degrees C and 40  degrees C. Generally, different temperatures had impacts
      on the physiological activity of A. cornea and the bacterial community in the
      substrate; therefore, the data presented herein should facilitate cultivation of
      A. cornea.

PMID- 30294485
TI  - Verticillium Wilt of Okra Caused by Verticillium dahliae Kleb. in China.
AB  - Okra (Abelmoschus esculentus (L.) Moench) has gained more popularity as an
      economically significant plant for its nutritional and medicinal value,
      especially in China. During 2014-2016, the root disease of okra was discovered in
      four okra commercial fields surveyed in China. A fungul was isolated from the
      infected tissues, and was identified by Verticillium dahliae based on
      morphological characteristics. Pathogenicity test demonstrated that the fungus
      was pathogenic on okra, and fulfilled Koch's postulates. The analysis of three
      sequences revealed 99-100% identity with the reported V. dahliae strain in
      GenBank. Neighbor-joining analysis of the gene sequences revealed that the
      representative isolates were clustered with V. dahliae. To the best of our
      knowledge, this is the first report of Verticillium wilt of okra in China.

PMID- 30294486
TI  - Discovery of Two Chrysosporium Species with Keratinolytic Activity from Field
      Soil in Korea.
AB  - In an ongoing survey of Korean indigenous fungi, two fungal strains (KNU16-74 and
      KNU16-99) belonging to the genus Chrysosporium were isolated from field soil in
      Gyeongnam, Korea. Morphological characterization and phylogenetic analysis using
      sequence of the internal transcribed spacer regions were carried out to confirm
      its precise identification. These strains were identified as Chrysosporium
      indicum (KNU16-74) and Chrysosporium fluviale (KNU16-99). To examine the keratin
      degradation efficiency of these two fungal species, human hair strands were
      incubated with fungus culture. Results revealed that these two fungal species
      have the ability to degrade keratin substrate. This is the first report of these
      two species in Korea.

PMID- 30294488
TI  - Morphology and Molecular Characterization of Alternaria argyranthemi on
      Chrysanthemum coronarium in China.
AB  - Chrysanthemum coronarium is an economically important plant in Asia, and used
      medicinally, ornamentally and as a vegetable. In April 2017, leaf spot disease on
      C. coronarium was observed in Shiyan, Hubei, China. A single-spore isolate was
      obtained and identified based on morphology and sequence analysis using four
      regions (rDNA ITS, GAPDH, EF-1alpha, and RPB2). The results indicated that the
      fungus is Alternaria argyranthemi. The pathogenicity tests revealed that the
      species could cause severe leaf spot and blight disease on the host. This is the
      first report of leaf spot disease on C. coronarium caused by A. argyranthemi in
      the world, which is also a new record of Alternaria species in China.

PMID- 30294487
TI  - Investigation of Filamentous Fungi Producing Safe, Functional Water-Soluble
      Pigments.
AB  - The production of water-soluble pigments by fungal strains indigenous to South
      Korea was investigated to find those that are highly productive in submerged
      culture. Among 113 candidates, 34 strains that colored the inoculated potato
      dextrose agar medium were selected. They were cultured in potato dextrose broth
      and extracted with ethanol. The productivity, functionality (radical-scavenging
      activities), and color information (CIELAB values) of the pigment extracts were
      measured. Five species produced intense yellowish pigments, and two produced
      intense reddish pigments that ranked the highest in terms of absorbance units
      produced per day. The pigment extracts of Penicillium miczynskii, Sanghuangporus
      baumii, Trichoderma sp. 1, and Trichoderma afroharzianum exhibited high radical
      scavenging activity. However, the S. baumii extract showed moderate toxicity in
      the acute toxicity test, which limits the industrial application of this pigment.
      In conclusion, P. miczynskii KUC1721, Trichoderma sp. 1 KUC1716, and T.
      afroharzianum KUC21213 were the best fungal candidates to be industrial producers
      of safe, functional water-soluble pigments.

PMID- 30294489
TI  - Timing of Fusarium Head Blight Infection in Rice by Heading Stage.
AB  - Fusarium graminearum causes the devastating plant disease Fusarium head blight
      and produces mycotoxins on small cultivated grains. To investigate the timeframe
      of F. graminearum infection during rice cultivation, a spore suspension of F.
      graminearum was applied to the rice cultivars Dongjin 1 and Nampyeongbyeo before
      and after the heading stage. The disease incidence rate was the highest (50%)
      directly after heading, when the greatest number of flowers were present, while
      only 10% of the rice infected 30 days after heading showed symptoms. To
      understand the mechanism of infection, an F. graminearum strain expressing green
      fluorescent protein (GFP) was inoculated, and the resulting infections were
      visually examined. Spores were found in all areas between the glume and inner
      seed, with the largest amount of GFP detected in the aleurone layer. When the
      inner part of the rice seed was infected, the pathogen was mainly observed in the
      embryo. These results suggest that F. graminearum migrates from the anthers to
      the ovaries and into the seeds during the flowering stage of rice. This study
      will contribute to uncovering the infection process of this pathogen in rice.

PMID- 30294490
TI  - Effect of Temperature and Relative Humidity on Growth of Aspergillus and
      Penicillium spp. and Biocontrol Activity of Pseudomonas protegens AS15 against
      Aflatoxigenic Aspergillus flavus in Stored Rice Grains.
AB  - In this study, we evaluated the effect of different temperatures (10, 20, 30, and
      40  degrees C) and relative humidities (RHs; 12, 44, 76, and 98%) on populations
      of predominant grain fungi (Aspergillus candidus, Aspergillus flavus, Aspergillus
      fumigatus, Penicillium fellutanum, and Penicillium islandicum) and the biocontrol
      activity of Pseudomonas protegens AS15 against aflatoxigenic A. flavus KCCM 60330
      in stored rice. Populations of all the tested fungi in inoculated rice grains
      were significantly enhanced by both increased temperature and RH. Multiple linear
      regression analysis revealed that one unit increase of temperature resulted in
      greater effects than that of RH on fungal populations. When rice grains were
      treated with P. protegens AS15 prior to inoculation with A. flavus KCCM 60330,
      fungal populations and aflatoxin production in the inoculated grains were
      significantly reduced compared with the grains untreated with strain AS15
      regardless of temperature and RH (except 12% RH for fungal population). In
      addition, bacterial populations in grains were significantly enhanced with
      increasing temperature and RH, regardless of bacterial treatment. Higher
      bacterial populations were detected in biocontrol strain-treated grains than in
      untreated control grains. To our knowledge, this is the first report showing
      consistent biocontrol activity of P. protegens against A. flavus population and
      aflatoxin production in stored rice grains under various environmental conditions
      of temperature and RH.

PMID- 30294491
TI  - Laboratory testing of a shuttle car canopy air curtain for respirable coal mine
      dust control.
AB  - Canopy air curtain (CAC) technology has been developed by the National Institute
      for Occupational Safety and Health (NIOSH) for use on continuous miners and
      subsequently roof bolting machines in underground coal mines to protect operators
      of these machines from overexposure to respirable coal mine dust. The next
      logical progression is to develop a CAC for shuttle cars to protect operators
      from the same overexposures. NIOSH awarded a contract to Marshall University and
      J.H. Fletcher to develop the shuttle car CAC. NIOSH conducted laboratory testing
      to determine the dust control efficiency of the shuttle car CAC. Testing was
      conducted on two different cab configurations: a center drive similar to that on
      a Joy 10SC32AA cab model and an end drive similar to that on a Joy 10SC32AB cab
      model. Three different ventilation velocities were tested-0.61, 2.0, 4.3 m/s
      (120, 400, and 850 fpm). The lowest, 0.61 m/s (120 fpm), represented the
      ventilation velocity encountered during loading by the continuous miner, while
      the 4.3 m/s (850 fpm) velocity represented ventilation velocity airflow over the
      shuttle car while tramming against ventilation airflow. Test results showed an
      average of the dust control efficiencies ranging from 74 to 83% for 0.61 m/s (120
      fpm), 39%-43% for 2.0 m/s (400 fpm), and 6%-16% for 4.3 m/s (850 fpm).
      Incorporating an airflow spoiler to the shuttle car CAC design and placing the
      CAC so that it is located 22.86 cm (9 in.) forward of the operator improved the
      dust control efficiency to 51%-55% for 4.3 m/s (850 fpm) with minimal impact on
      dust control efficiencies for lower ventilation velocities. These laboratory
      tests demonstrate that the newly developed shuttle car CAC has the potential to
      successfully protect shuttle car operators from coal mine respirable dust
      overexposures.

PMID- 30294492
TI  - Infrared thermography brain mapping surveillance in vascular neurosurgery for
      anterior communicating artery aneurysm clipping.
AB  - Background: Infrared thermography (IT) is a noninvasive, real-time diagnostic
      method that requires no contact with the patient and has a broad spectrum of
      potential applications in neurosurgery. It has been previously demonstrated the
      high sensitivity and specificity that IT has to detect brain blood flow changes.
      Case Description: The case is based on a 64-year-old diabetic and hypertensive
      male, to whom an anterior communicating artery (ACoA) incidental aneurysm was
      discovered. We performed the basal infrared thermography mapping (ITM) and
      immediately after the transitory clip placement in both A1 segments of the
      anterior cerebral artery (A1-ACA), we performed a second ITM of the exposed brain
      cortex. After the definitive clip placement in the neck of the ACoA aneurysm, we
      removed the transitory clips of both A1-ACA and performed a third ITM of the
      cortical surface, without finding any cortical cooling or significative
      temperature differences (?t) compared to the basal ITM. The postoperatory
      computed tomography (CT) and angio-CT did not show any ischemic damage and
      confirmed the accurate aneurysm clipping. Conclusions: The ITM seems to be a real
      time, safe, and useful brain mapping method to identify different temperature
      zones and temperature dispersion gradients in the human brain cortex. More
      studies are needed to evaluate the potential applications of IT mapping of the
      human brain and its use in neurosurgery and vascular neurosurgery.

PMID- 30294494
TI  - Compartment syndrome of lumbar paraspinal musculature after percutaneous pedicle
      screw fixation.
AB  - Background: Compartment syndromes have been reported in nearly every anatomical
      area of the extremities. Similarly, in the lumbar spine, there is a risk of a
      compartment syndrome following either direct or indirect injury to the paraspinal
      muscles. In this study, we present a case of lumbar paraspinal compartment
      syndrome after percutaneous pedicle screw fixation for a spine fracture. Case
      Description: A 27-year-old obese female sustained a fall and an L1 fracture. Her
      neurological examination was normal. She underwent a minimally invasive
      percutaneous posterior pedicle screw fixation from T12 to L2 to stabilize the L1
      fracture. Postoperatively, the patient developed hypoesthesia in the back, and
      sterile serous wound discharge. Because of the persistent discharge, an open
      debridement was performed that revealed multiple cavities within the necrotic
      avascular paraspinal musculature. Once these were completely excised, the wounds
      healed uneventfully. Conclusion: Patients undergoing minimally invasive posterior
      thoracolumbar (TL) pedicle screw fixation can develop a compartment syndrome
      involving the TL paraspinal musculature. This case highlights the need for early
      consideration of a compartment syndrome when patients develop persistent sterile
      discharge after spine surgery. In this case, urgent decompression prevented any
      long-term sequelae.

PMID- 30294493
TI  - Fusiform aneurysms: A review from its pathogenesis to treatment options.
AB  - Background: This study aims to present the most important considerations when it
      comes to patients features, clinical presentation, localization, and morphology
      of the aneurysm and the treatments outcomes of the fusiform aneurysms. Methods:
      We performed a literature review using PubMed. The search was limited to the
      studies published in English, from 2003 to 2017. Results: The studies analyzed
      that showed data about the patient features, clinical presentation, the aneurysm
      localization, morphology, and pathogenesis didn't present much divergence. The
      surgical and the endovascular approach showed similar treatments outcomes. The
      reconstructive techniques seem to be safer than the deconstructive. The flow
      diversion is a technique that showed great results. Conclusion: Most of the
      patients are men, younger than 50 years old, pediatric patients are the most
      affected. Surgical procedures still have an important place in this field.
      Reconstructive and deconstructive techniques are both effective; the
      reconstructive techniques are possibly safer than deconstructive techniques. The
      most important feature of an aneurysm to predict a bad prognose is to determine
      if the aneurysm is ruptured. The reconstructive EVT accompanied by dual
      antiplatelet after and before the procedure showed the best results to treat the
      basilar fusiform aneurysms. Deconstructive treatment including posterior inferior
      cerebellar artery occlusion should be considered.

PMID- 30294495
TI  - Myxopapillary ependymoma with anaplastic features: A case report with review of
      the literature.
AB  - Background: Myxopapillary ependymoma (MPE) with anaplastic features is extremely
      rare, with only three case reports in the literature. Case Description: We report
      the case of a MPE with anaplastic features in a 24-year-old female who presented
      with a dominant lumbar mass along with intracranial and sacral metastases. Upon
      gross total resection of the dominant tumor located at L2-L3, it appeared to
      arise from the filum terminale, and had a solid component in addition to soft or
      necrotic areas. Histologically, the tumor was composed of the two classic
      components of MPE: (1) low-grade ependymal cells surrounding blood vessels,
      producing the papillary appearance and (2) perivascular myxoid material between
      blood vessels and ependymal cells, creating the myxopapillary appearance. The
      high-grade anaplastic component showed hypercellularity, brisk mitotic rate, and
      vascular proliferation, with frequent pleomorphic cells and atypical mitotic
      figures. It was positive for vimentin and glial fibrillary acidic protein (GFAP);
      negative for epithelial membrane antigen (EMA), CAM5.2, creatine kinase 7 (CK7),
      CK20; and the MIB-1 index (Ki-67) was 8-38%. Ten months after initial resection,
      follow-up magnetic resonance imaging revealed new lesions in (1) the
      hypothalamus, (2) the left pons, and (3) the left medial temporal lobe, which
      were treated with radiosurgery. Eight months later (18 months from initial
      surgery), the patient underwent thoracic laminectomy for a large leptomeningeal
      metastasis at T6 and T8. Conclusion: The present case of MPE with anaplastic
      features is the fourth case on record in the medical literature.

PMID- 30294496
TI  - Aneurysm of lenticulostriate artery in a patient presenting with hemorrhage in
      the caudate nucleus and lateral ventricle-delayed appearance and spontaneous
      resolution.
AB  - Background: An aneurysm of distal lenticulostriate artery is very rare. The
      natural course and management of this rare aneurysm are not clear. Case
      Description: An 81-year-old woman developed consciousness disturbance. Computed
      tomography revealed hemorrhage in the right caudate nucleus and lateral
      ventricles. Three-dimensional computed tomographic angiography demonstrated only
      an aneurysm at the basilar artery. On angiography, on the sixth day, an aneurysm
      at the right lenticulostriate artery was demonstrated. Then, the aneurysm
      disappeared on three-dimensional computed tomographic angiography on the 15th
      day. Subsequent radiological examinations revealed no vascular anomaly in the
      right lenticulostriate artery. Conclusion: An aneurysm at this location can show
      dynamic changes based on radiological findings. Close radiological observation is
      necessary.

PMID- 30294497
TI  - An unusual presentation of dystonia and chorea from intraventricular
      pneumocephalus.
AB  - Background: Pneumocephalus is a common finding following intracranial procedures,
      typically asymptomatic and resolves within several days. However, in some cases,
      pneumocephalus presents with headache, encephalopathy, or symptoms of elevated
      intracranial pressure. Here, we present a case of iatrogenic tension
      pneumocephalus following endoscopic sinus surgery, presenting as abnormal
      involuntary movements resembling a movement disorder with choreiform movements.
      Case Description: A 67-year-old previously healthy male presented with new onset
      chorea and dystonia associated with headache, encephalopathy, and postural
      instability 4 days after undergoing endoscopic sinus surgery for chronic
      sinusitis and nasal polyps. Computed tomography showed prominent intraventricular
      pneumocephalus causing enlargement of the anterior horns of both lateral
      ventricles with lateral displacement of the basal ganglia nuclei and a bony
      defect in the skull base. Neurosurgical correction of the cranial defect provided
      complete symptomatic resolution. Pneumocephalus as a result of an iatrogenic
      injury of the skull base manifesting as an acute movement disorder is a rare
      complication of a nasal sinus procedure. We speculate that compression of the
      caudate nucleus and striatum resulted in decreased pallidothalamic inhibition and
      thalamocortical disinhibition leading to the development of a hyperkinetic
      movement disorder. Conclusion: This unusual presentation of a common procedure
      illustrates a neurological emergency that requires prompt recognition and timely
      correction.

PMID- 30294498
TI  - A rare cause of thoracic cord compression.
AB  - Background: The posterior longitudinal ligament (PLL) extends from the foramen
      magnum to the sacrum. In some cases, it becomes calcified/ossified; the term for
      this is ossification of the PLL (OPLL). Case Description: A 50-year-old female
      presented with acute sphincter dysfunction and paraparesis attributed to T2-T4
      OPLL. The patient underwent a C7-T5 laminectomy to decompress the spinal cord.
      After 1 postoperative week, and certainly by 6 months postoperatively, the
      patient's motor and sensory deficits showed improvement. Conclusion: Surgery for
      thoracic OPLL includes laminoplasty, laminectomy with/without fusion, anterior
      decompression through a posterior approach (transpedicular,
      costotransversectomy), and circumferential decompression (e.g. combined
      anterior/posterior approaches). In cases like the one presented, patients who
      originally present with acute paraparesis/sphincter dysfunction may demonstrate
      postoperative improvement.

PMID- 30294499
TI  - Cerebrospinal fluid drainage and blood pressure elevation to treat acute spinal
      cord infarct.
AB  - Background: Current management of acute spinal cord infarction (SCI) is limited.
      Lumbar cerebrospinal fluid drainage (CSFD) with blood pressure augmentation is
      utilized in the thoracic/thoracoabdominal aortic repair and thoracic endovascular
      aortic repair (TEVAR) populations to increase spinal perfusion pressure. Case
      description: We identified 3 patients who sustained acute SCI and underwent CSFD
      and maintenance of elevated mean arterial pressure (MAP) within 24 hours of
      injury. The first patient exhibited delayed-onset ischemia after a TEVAR. The
      second patient presented with an acute type B aortic intramural hematoma. The
      third patient developed spinal cord ischemia following bronchial artery
      embolization. There was significant improvement in the motor examination (e.g.,
      ASIA impairment scale grade B or C) to grade D utilizing both blood pressure
      augmentation and CSFD. Conclusions: Lumbar CSFD with MAP elevation benefited 3
      patients with acute SCI of varying etiologies.

PMID- 30294500
TI  - Using Heatmaps to Identify Opportunities for Optimization of Test Utilization and
      Care Delivery.
AB  - Background: When a provider orders a test in a pattern that is substantially
      different than their peers, it may indicate confusion in the test name or
      inappropriate use of the test, which can be elucidated by initiating dialog
      between clinicians and the laboratory. However, the analysis of ordering patterns
      can be challenging. We propose a utilization index (UI) as a means to quantify
      utilization patterns for individual providers and demonstrate the use of heatmaps
      to identify opportunities for improvement. Materials and Methods: Laboratory test
      orders by all providers were extracted from the laboratory information system.
      Providers were grouped into cohorts based on the specialty and patient
      population. A UI was calculated for each provider's use of each test using the
      following formula: (UI = [provider volume of specific test/provider volume of all
      tests]/[cohort volume of specific test/cohort volume of all tests]). A heatmap
      was generated to compare each provider to their cohort. Results: This method
      identified several hot spots and was helpful in reducing confusion and
      overutilization. Conclusion: The UI is a useful measure of test ordering
      behavior, and heatmaps provide a clear visual illustration of the utilization
      indices. This information can be used to identify areas for improvement and
      initiate meaningful dialog with providers, which will ultimately bring
      improvement and reduction in costs. Our method is simple and uses resources that
      are widely available, making this method effective convenient for many other
      laboratories.

PMID- 30294502
TI  - Innovation in Transplantation: The Digital Era.
AB  - The international symposium entitled "Innovation in Transplantation: The Digital
      Era" took place on June 7 and 8, 2018 in Verona, Italy. This meeting was borne
      out of the productive collaboration between the Universities and Hospital Trusts
      of Verona and Padua in Italy, in the context of a vast regional project called
      Research and innovation project within the Health Technology Assessment. The
      project aimed to create an innovative digital platform for teleconsultation and
      delivering diagnostic second opinions in the field of organ transplantation
      within the Veneto region. This conference brought together pathologists, health
      informatics leaders, clinicians, researchers, vendors, and health-care planners
      from all around the globe. The symposium was conceived to promote the exchange of
      knowledge and kindle fertile discussion among the 130 attendees from 15 different
      countries. This article conveys the highlights of this symposium.

PMID- 30294501
TI  - Diagnostic Performance of Deep Learning Algorithms Applied to Three Common
      Diagnoses in Dermatopathology.
AB  - Background: Artificial intelligence is advancing at an accelerated pace into
      clinical applications, providing opportunities for increased efficiency, improved
      accuracy, and cost savings through computer-aided diagnostics. Dermatopathology,
      with emphasis on pattern recognition, offers a unique opportunity for testing
      deep learning algorithms. Aims: This study aims to determine the accuracy of deep
      learning algorithms to diagnose three common dermatopathology diagnoses. Methods:
      Whole slide images (WSI) of previously diagnosed nodular basal cell carcinomas
      (BCCs), dermal nevi, and seborrheic keratoses were annotated for areas of
      distinct morphology. Unannotated WSIs, consisting of five distractor diagnoses of
      common neoplastic and inflammatory diagnoses, were included in each training set.
      A proprietary fully convolutional neural network was developed to train
      algorithms to classify test images as positive or negative relative to ground
      truth diagnosis. Results: Artificial intelligence system accurately classified
      123/124 (99.45%) BCCs (nodular), 113/114 (99.4%) dermal nevi, and 123/123 (100%)
      seborrheic keratoses. Conclusions: Artificial intelligence using deep learning
      algorithms is a potential adjunct to diagnosis and may result in improved
      workflow efficiencies for dermatopathologists and laboratories.

PMID- 30294503
TI  - Ring Expansion of Bicyclic Methyleneaziridines via Concerted, Near-Barrierless
      [2,3]-Stevens Rearrangements of Aziridinium Ylides.
AB  - The synthesis of densely functionalized azetidinesin a highly stereocontrolled
      manner is challenging, but interest in the bioactivities of these small
      heterocycles has stimulated methods for their preparation. We recently reported a
      one-carbon ring expansion of bicyclic methylene aziridines under dirhodium
      catalysis capable of delivering enantioenriched azetidines. This work explores
      this ring expansion using computational and experimental studies. DFT
      computations indicate that the reaction proceeds through formation of an
      aziridinium ylide, which is precisely poised for concerted, asynchronous ring
      opening/closing to deliver the azetidines in a [2,3]-Stevens-type rearrangement.
      The concerted nature of this rearrangement is responsible for the
      stereospecificity of the reaction, where axial chirality from the initial allene
      substrate is transferred to the azetidine product with complete fidelity. The
      computed mechanistic pathway highlights the key roles of the olefin and the rigid
      structure of the methylene aziridine in differentiating our observed ring
      expansion from competing cheletropic elimination pathways noted with ylides
      derived from typical aziridines.

PMID- 30294504
TI  - Development of de Novo Copper Nitrite Reductases: Where We Are and Where We Need
      To Go.
AB  - The development of redox-active metalloprotein catalysts is a challenging
      objective of de novo protein design. Within this Perspective we detail our
      efforts to create a redox-active Cu nitrite reductase (NiR) by incorporating Cu
      into the hydrophobic interior of well-defined three-stranded coiled coils
      (3SCCs). The scaffold contains three histidine residues that provide a layer of
      three nitrogen donors that mimic the type 2 catalytic site of NiR. We have found
      that this strategy successfully produces an active and stable CuNiR model that
      functions for over 1000 turnovers. Spectroscopic evidence indicates that the
      Cu(I) site has a lower coordination number in comparison to the enzyme, whereas
      the Cu(II) geometry may more faithfully reproduce the NiR type 2 center.
      Mutations at the helical interface successfully produce a hydrogen bond between
      an interfacial Glu residue and the Culigating His residue, which allows for the
      tuning of the redox potential over a 100 mV range. We successfully created
      constructs with as much as a 120-fold improvement from the original design by
      modifying the steric bulk above or below the Cu binding site. These systems are
      now the most active water-soluble and stable artificial NiR catalysts yet
      produced. Several avenues for improving the catalytic efficiency of later designs
      are detailed within this Perspective, including adjustment of their resting
      oxidation state, the use of asymmetric scaffolds to allow for single amino acid
      mutation within the second coordination sphere, and the design of hydrogen
      bonding networks to tune residue orientation and electronics. Through these
      studies the TRI-H system has given insight into the difficulties that arise in
      creating a de novo redox active enzyme. Work to improve upon this model will
      provide strategies by which redox-active de novo enzymes may be tuned and detail
      how native enzymes accomplish catalytic efficiencies through proton gated redox
      catalysis.

PMID- 30294505
TI  - Impact of Infant-Polysomnography Studies on Discharge Management and Outcomes: A
      5 Year Experience from a Tertiary Care Unit.
AB  - Objective: To evaluate the impact of infant-polysomnography studies performed in
      the NICU on management and outcomes. Study design: Retrospective study to collect
      demographics and data on infant-polysomnography studies between Jan 2010 to Dec
      2014. Results: 110 premature neonates had polysomnography study performed at 36.9
      +/- 2.5 weeks post menstrual age. Almost all the studies were read as abnormal
      and 95% of the studied infants were discharged home on a cardiorespiratory
      monitor. 20% of the subjects had apnea >20 s, 18% had apnea of 15-20 s and 50% of
      infants had apnea of 10-15 s. 24.5% infants were discharged home on caffeine, 28%
      on metoclopramide and 24% on antacids. There were 11 readmissions for apparent
      life threatening events with no until 6 month-corrected age. There was no
      association between polysomnography results and readmission. There was a decline
      in polysomnography studies performed each year. Conclusion: Cardiorespiratory
      monitoring, medications and polysomnography studies do not predict outcomes.

PMID- 30294506
TI  - Microbial interactions with the intestinal epithelium and beyond: Focusing on
      immune cell maturation and homeostasis.
AB  - Microbial metabolites influence the function of epithelial, endothelial and
      immune cells in the intestinal mucosa. Microbial metabolites like SCFAs and B
      complex vitamins direct macrophage polarization whereas microbial derived
      biogenic amines modulate intestinal epithelium and immune response. Aberrant
      bacterial lipopolysaccharide-mediated signaling may be involved in the
      pathogenesis of chronic intestinal inflammation and colorectal carcinogenesis.
      Our perception of human microbes has changed from that of opportunistic pathogens
      to active participants maintaining intestinal and whole body homeostasis. This
      review attempts to explain the dynamic and enriched interactions between the
      intestinal epithelial mucosa and commensal bacteria in homeostasis maintenance.

PMID- 30294507
TI  - Can secondary contact following range expansion be distinguished from barriers to
      gene flow?
AB  - Secondary contact is the reestablishment of gene flow between sister populations
      that have diverged. For instance, at the end of the Quaternary glaciations in
      Europe, secondary contact occurred during the northward expansion of the
      populations which had found refugia in the southern peninsulas. With the advent
      of multi-locus markers, secondary contact can be investigated using various
      molecular signatures including gradients of allele frequency, admixture clines,
      and local increase of genetic differentiation. We use coalescent simulations to
      investigate if molecular data provide enough information to distinguish between
      secondary contact following range expansion and an alternative evolutionary
      scenario consisting of a barrier to gene flow in an isolation-by-distance model.
      We find that an excess of linkage disequilibrium and of genetic diversity at the
      suture zone is a unique signature of secondary contact. We also find that the
      directionality index psi, which was proposed to study range expansion, is
      informative to distinguish between the two hypotheses. However, although evidence
      for secondary contact is usually conveyed by statistics related to admixture
      coefficients, we find that they can be confounded by isolation-by-distance. We
      recommend to account for the spatial repartition of individuals when
      investigating secondary contact in order to better reflect the complex spatio
      temporal evolution of populations and species.

PMID- 30294508
TI  - Transkingdom network reveals bacterial players associated with cervical cancer
      gene expression program.
AB  - Cervical cancer is the fourth most common cancer in women worldwide with human
      papillomavirus (HPV) being the main cause the disease. Chromosomal amplifications
      have been identified as a source of upregulation for cervical cancer driver genes
      but cannot fully explain increased expression of immune genes in invasive
      carcinoma. Insight into additional factors that may tip the balance from immune
      tolerance of HPV to the elimination of the virus may lead to better diagnosis
      markers. We investigated whether microbiota affect molecular pathways in cervical
      carcinogenesis by performing microbiome analysis via sequencing 16S rRNA in tumor
      biopsies from 121 patients. While we detected a large number of intra-tumor taxa
      (289 operational taxonomic units (OTUs)), we focused on the 38 most abundantly
      represented microbes. To search for microbes and host genes potentially involved
      in the interaction, we reconstructed a transkingdom network by integrating a
      previously discovered cervical cancer gene expression network with our bacterial
      co-abundance network and employed bipartite betweenness centrality. The top
      ranked microbes were represented by the families Bacillaceae, Halobacteriaceae,
      and Prevotellaceae. While we could not define the first two families to the
      species level, Prevotellaceae was assigned to Prevotella bivia. By co-culturing a
      cervical cancer cell line with P. bivia, we confirmed that three out of the ten
      top predicted genes in the transkingdom network (lysosomal associated membrane
      protein 3 (LAMP3), STAT1, TAP1), all regulators of immunological pathways, were
      upregulated by this microorganism. Therefore, we propose that intra-tumor
      microbiota may contribute to cervical carcinogenesis through the induction of
      immune response drivers, including the well-known cancer gene LAMP3.

PMID- 30294509
TI  - Geopolitical species revisited: genomic and morphological data indicate that the
      roundtail chub Gila robusta species complex (Teleostei, Cyprinidae) is a single
      species.
AB  - The Gila robusta species complex in the Lower Colorado River Basin has a
      complicated taxonomic history. Recent authors have separated this group into
      three nominal taxa, G. robusta, G. intermedia, and G. nigra, however aside from
      location, no reliable method of distinguishing individuals of these species
      currently exists. To assess relationships within this group, we examined
      morphology of type specimens and fresh material, and used RADseq methods to
      assess phylogenetic relationship among these nominal species. Maximum likelihood
      and Bayesian inference tree building methods reveal high concordance between tree
      topologies based on the mitochondrial and nuclear datasets. Coalescent SNAPP
      analysis resolved a similar tree topology. Neither morphological nor molecular
      data reveal diagnostic differences between these species as currently defined. As
      such, G. intermedia and G. nigra should be considered synonyms of the senior G.
      robusta. We hypothesize that climate driven wet and dry cycles have led to
      periodic isolation of population subunits and subsequent local divergence
      followed by reestablished connectivity and mixing. Management plans should
      therefore focus on retaining genetic variability and viability of geographic
      populations to preserve adaptability to changing climate conditions.

PMID- 30294510
TI  - An adaptive scale Gaussian filter to explain White's illusion from the viewpoint
      of lightness assimilation for a large range of variation in spatial frequency of
      the grating and aspect ratio of the targets.
AB  - The variation between the actual and perceived lightness of a stimulus has strong
      dependency on its background, a phenomena commonly known as lightness induction
      in the literature of visual neuroscience and psychology. For instance, a gray
      patch may perceptually appear to be darker in a background while it looks
      brighter when the background is reversed. In the literature it is further
      reported that such variation can take place in two possible ways. In case of
      stimulus like the Simultaneous Brightness Contrast (SBC), the apparent lightness
      changes in the direction opposite to that of the background lightness, a
      phenomenon often referred to as lightness contrast, while in the others like neon
      colour spreading or checkerboard illusion it occurs opposite to that, and known
      as lightness assimilation. The White's illusion is a typical one which according
      to many, does not completely conform to any of these two processes. This paper
      presents the result of quantification of the perceptual strength of the White's
      illusion as a function of the width of the background square grating as well as
      the length of the gray patch. A linear filter model is further proposed to
      simulate the possible neurophysiological phenomena responsible for this
      particular visual experience. The model assumes that for the White's illusion,
      where the edges are strong and quite a few, i.e., the spectrum is rich in high
      frequency components, the inhibitory surround in the classical Difference-of
      Gaussians (DoG) filter gets suppressed, and the filter essentially reduces to an
      adaptive scale Gaussian kernel that brings about lightness assimilation. The
      linear filter model with a Gaussian kernel is used to simulate the White's
      illusion phenomena with wide variation of spatial frequency of the background
      grating as well as the length of the gray patch. The appropriateness of the model
      is presented through simulation results, which are highly tuned to the present as
      well as earlier psychometric results.

PMID- 30294511
TI  - De novo transcriptome sequencing and analysis of genes related to salt stress
      response in Glehnia littoralis.
AB  - Soil salinity is one of the major environmental stresses affecting plant growth,
      development, and reproduction. Salt stress also affects the accumulation of some
      secondary metabolites in plants. Glehnia littoralis is an endangered medicinal
      halophyte that grows in coastal habitats. Peeled and dried Glehnia littoralis
      roots, named Radix Glehniae, have been used traditionally as a Chinese herbal
      medicine. Although Glehnia littoralis has great ecological and commercial value,
      salt-related mechanisms in Glehnia littoralis remain largely unknown. In this
      study, we analysed the transcriptome of Glehnia littoralis in response to salt
      stress by RNA-sequencing to identify potential salt tolerance gene networks.
      After de novo assembly, we obtained 105,875 unigenes, of which 75,559 were
      annotated in public databases. We identified 10,335 differentially expressed
      genes (DEGs; false discovery rate <0.05 and |log2 fold-change| >= 1) between NaCl
      treatment (GL2) and control (GL1), with 5,018 upregulated and 5,317 downregulated
      DEGs. To further this investigation, we performed Gene Ontology (GO) analysis and
      the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. DEGs
      involved in secondary metabolite biosynthetic pathways, plant signal transduction
      pathways, and transcription factors in response to salt stress were analysed. In
      addition, we tested the gene expression of 15 unigenes by quantitative real-time
      PCR (qRT-PCR) to confirm the RNA-sequencing results. Our findings represent a
      large-scale assessment of the Glehnia littoralis gene resource, and provide
      useful information for exploring its molecular mechanisms of salt tolerance.
      Moreover, genes enriched in metabolic pathways could be used to investigate
      potential biosynthetic pathways of active compounds by Glehnia littoralis.

PMID- 30294513
TI  - Periwinkle climbing response to water- and airbone predator chemical cues may
      depend on home-marsh geography.
AB  - The salt marsh periwinkle, Littorina irrorata, exhibits a spatial refuge from
      predation by climbing the stems of Spartina alterniflora in order to avoid
      benthic predators. Salt marsh periwinkles have a broad geographic distribution,
      and for many species, responses to predators also varies with biogeography. This
      study sought to determine if the geographical location of the home marsh
      influenced the response of periwinkles (climbing height) to blue crab predator
      cues both via air and water. Snails from Louisiana (LA) climbed higher in general
      than those from North Carolina (NC), regardless of chemical cue. However, LA
      snails climbed 11 cm higher in the presence of waterborne predators than control
      snails with no cue, while NC snails only climbed five cm higher in the same
      comparisons. Airborne chemical cue tended to have snails climbing at intermediate
      heights. These responses were significantly enhanced when both populations of
      snails were housed together. Periwinkle response to predator cues was stronger in
      LA than NC, and so it is possible that the behavioral response of these snails to
      predators varies with biogeography of the home marsh. Also interestingly, the
      results of this study also suggest that cue delivery is probably occurring via
      mechanisms other than water, and potentially via airborne cues. Therefore, salt
      marsh periwinkles likely respond to numerous cues that initiate behavioral
      responses, including airborne cues, and these responses may vary by home-marsh
      geography.

PMID- 30294512
TI  - Age, but not short-term intensive swimming, affects chondrocyte turnover in
      zebrafish vertebral cartilage.
AB  - Both age and intensive exercise are generally considered critical risk factors
      for osteoarthritis. In this work, we intend to establish zebrafish models to
      assess the role of these two factors on cartilage homeostasis. We designed a
      swimming device for zebrafish intensive exercise. The body measurements, bone
      mineral density (BMD) and the histology of spinal cartilages of 4- and 12-month
      old zebrafish, as well the 12-month-old zebrafish before and after a 2-week
      exercise were compared. Our results indicate that both age and exercise affect
      the body length and body weight, and the micro-computed tomography reveals that
      both age and exercise affect the spinal BMD. However, quantitative analysis of
      immunohistochemistry and histochemistry indicate that short-term intensive
      exercise does not affect the extracellular matrix (ECM) of spinal cartilage. On
      the other hand, the cartilage ECM significantly grew from 4 to 12 months of age
      with an increase in total chondrocytes. dUTP nick end labeling staining shows
      that the percentages of apoptotic cells significantly increase as the zebrafish
      grows, whereas the BrdU labeling shows that proliferative cells dramatically
      decrease from 4 to 12 months of age. A 30-day chase of BrdU labeling shows some
      retention of labeling in cells in 4-month-old spinal cartilage but not in
      cartilage from 12-month-old zebrafish. Taken together, our results suggest that
      zebrafish chondrocytes are actively turned over, and indicate that aging is a
      critical factor that alters cartilage homeostasis. Zebrafish vertebral cartilage
      may serve as a good model to study the maturation and homeostasis of articular
      cartilage.

PMID- 30294514
TI  - Direct and indirect effects of pesticides on a benthic grazer during its life
      cycle.
AB  - Background: Macroinvertebrates in aquatic ecosystems are repeatedly exposed to
      pesticides during their life cycle. Effects of consecutive exposure during
      different life stages and possible synergistic effects are not addressed in the
      standardized hazard assessment. The present study investigated two
      environmentally relevant exposure scenarios in batch (microcosm) and artificial
      indoor stream (mesocosm) experiments using the larvae of the mayfly Rhithrogena
      semicolorata (grazer) and natural aufwuchs. Grazers were analysed regarding
      growth, physiological condition, and drift behaviour, while the aufwuchs was
      analysed in terms of biomass using the particulate organic carbon as well as the
      chlorophyll a content. The aim was to reveal direct and indirect effects of an
      herbicide exposure during autumn on juvenile grazers and an insecticide exposure
      during spring on semi-juvenile grazers. Results: Direct and indirect effects were
      found in both exposure scenarios at environmentally relevant concentrations. In
      the herbicide exposure scenario with terbutryn, clear direct effects on the
      aufwuchs community with a LOEC of 0.38 ug L-1 were found. Effect levels of
      grazers due to indirect effects were equal, with the overnight drift being the
      most sensitive grazer endpoint. In the insecticide exposure scenario, clear
      lethal and sub lethal effects of lambda-cyhalothrin were evident. Derived LC50
      values for the artificial indoor stream and batch experiment were 2.42 ug g-1 OC
      (69 days) and 1.2 ug g-1 OC (28 days), respectively. Sub lethal effects in terms
      of increased drift as well-reduced growth and triglyceride levels were found at
      concentrations of 1.4 and 0.09 ug g-1 OC (LOECs). These results were confirmed by
      the batch experiment, which revealed effect values in the similar range. Finally,
      a clear indirect effect of the insecticide on the aufwuchs was evident in the
      batch experiment with an LOEC at 0.9 ug g-1 OC. Conclusion: Toxicity Exposure
      Ratios calculated with the derived effect values indicate a risk for the
      investigated grazer by both pesticides. Moreover, observed indirect effects
      during the herbicide exposure seem to be able to affect the grazers during a
      second exposure with an insecticide, due to reduced physiological conditions. We
      suggest further research with time-shifted exposure scenarios to gain a better
      understanding of the complex interactions of pesticides with the life cycle and
      the food webs of macroinvertebrates.

PMID- 30294515
TI  - Modelling effects of time-variable exposure to the pyrethroid beta-cyfluthrin on
      rainbow trout early life stages.
AB  - Background: Available literature and regulatory studies show that the severity of
      effects of beta-cyfluthrin (a synthetic pyrethroid) on fish is influenced by the
      magnitude and duration of exposure. To investigate how the exposure pattern to
      beta-cyfluthrin (constant vs peak) may influence the response of the fish, we
      used a mechanistic effect model to predict the survival and growth of the rainbow
      trout over its early life stages (i.e. egg, alevin and swim-up fry). We
      parameterized a toxicokinetic-toxicodynamic (TKTD) module in combination with a
      dynamic energy budget model enabling us to describe uptake and elimination, as
      well as to predict the threshold concentration for survival and sublethal effects
      (feeding behaviour and growth). This effect model was calibrated using data from
      an early life stage experiment where trout was exposed to a constant
      concentration of cyfluthrin. The model was validated by comparing model
      predictions to independent data from a pulsed-exposure study with early life
      stages of rainbow trout. Results: The co-occurrence of effects on behaviour and
      growth raised the possibility that these were interrelated, i.e. impairment of
      feeding behaviour may have led to reduced food intake and slower growth. We,
      therefore, included 'effect on feeding' as mode of action in the TKTD module. At
      higher concentrations, the constant exposure led to death. The model was able to
      adequately capture this effect pattern in the calibration. The model was able to
      adequately predict the response of fish eggs, alevins and swim-up fry, from both
      the qualitative (response pattern) and quantitative points of view. Conclusions:
      Since the model was successfully validated, it can be used to predict survival
      and growth of early life stages under various realistic time-variable exposure
      profiles (e.g. profiles from FOCUS surface water modelling) of beta-cyfluthrin.

PMID- 30294516
TI  - Systematic miRNome profiling reveals differential microRNAs in transgenic maize
      metabolism.
AB  - Background: While some genetically modified organisms (GMOs) are created to
      produce new double-stranded RNA molecules (dsRNA), in others, such molecules may
      occur as an unintended effect of the genetic engineering process. Furthermore,
      GMOs might produce naturally occurring dsRNA molecules in higher or lower
      quantities than its non-transgenic counterpart. This study is the first to use
      high-throughput technology to characterize the miRNome of commercialized GM maize
      events and to investigate potential alterations in miRNA regulatory networks.
      Results: Thirteen different conserved miRNAs were found to be dys-regulated in GM
      samples. The insecticide Bt GM variety had the most distinct miRNome. These
      miRNAs target a range of endogenous transcripts, such as transcription factors
      and nucleic acid binding domains, which play key molecular functions in basic
      genetic regulation. In addition, we have identified 20 potential novel miRNAs
      with target transcripts involved in lipid metabolism in maize. isomiRs were also
      found in 96 conserved miRNAs sequences, as well as potential transgenic miRNA
      sequences, which both can be a source of potential off-target effects in the
      plant genome. We have also provided information on technical limitations and when
      to carry on additional in vivo experimental testing. Conclusions: These findings
      do not reveal hazards per se but show that robust and reproducible miRNA
      profiling technique can strengthen the assessment of risk by detecting any new
      intended and unintended dsRNA molecules, regardless of the outcome, at any stage
      of GMO development.

PMID- 30294517
TI  - Knowledge-based biomedical Data Science.
AB  - Computational manipulation of knowledge is an important, and often under
      appreciated, aspect of biomedical Data Science. The first Data Science initiative
      from the US National Institutes of Health was entitled "Big Data to Knowledge
      (BD2K)." The main emphasis of the more than $200M allocated to that program has
      been on "Big Data;" the "Knowledge" component has largely been the implicit
      assumption that the work will lead to new biomedical knowledge. However, there is
      long-standing and highly productive work in computational knowledge
      representation and reasoning, and computational processing of knowledge has a
      role in the world of Data Science. Knowledge-based biomedical Data Science
      involves the design and implementation of computer systems that act as if they
      knew about biomedicine. There are many ways in which a computational approach
      might act as if it knew something: for example, it might be able to answer a
      natural language question about a biomedical topic, or pass an exam; it might be
      able to use existing biomedical knowledge to rank or evaluate hypotheses; it
      might explain or interpret data in light of prior knowledge, either in a Bayesian
      or other sort of framework. These are all examples of automated reasoning that
      act on computational representations of knowledge. After a brief survey of
      existing approaches to knowledge-based data science, this position paper argues
      that such research is ripe for expansion, and expanded application.

PMID- 30294519
TI  - SCIT with a high-dose house dust mite allergoid is well tolerated: safety data
      from pooled clinical trials and more than 10 years of daily practice analyzed in
      different subgroups.
AB  - Background: Efficacy of house dust mite (HDM) allergen immunotherapy (AIT) in
      allergic rhinitis and controlled allergic asthma has been documented in
      controlled trials with adults and children. However, tolerability comparing
      clinical development and post marketing data, particularly in different
      subgroups, is missing. Methods: We performed an analysis of pooled safety data
      for subcutaneous AIT (SCIT) with a high-dose house dust mite allergoid from 6
      randomized, controlled trials (RCT) in HDM allergic respiratory disease (ARD) and
      of post marketing safety data from more than 10 years including different
      subgroups (age, gender, asthma status). Results: In all, 500 patients with ARD
      were treated in RCTs: 279 received the marketed dose of 1800 protein nitrogen
      units (PNU) high-dose HDM allergoid AIT (214 double-blind placebo controlled [HDM
      DBPC], 65 children/adolescents usual care controlled [HDM-RCT(UC)]), and 221
      placebo (PL). 38.8% adverse events (AEs) were observed with 1800 PNU in HDM-DBPC
      (31.2% PL, 35.5% HDM-ALL [1800 PNU]); the difference was primarily because of
      local reactions; there was no difference in systemic reactions (10.9% PL, 11.2%
      HDM-DBPC, 11.2% HDM-ALL); one out of 279 high-dose HDM allergoid-treated patients
      had a serious adverse event (SAE).Children (n = 39)/adolescents (n = 26) had
      fewer related AEs and local reactions compared to adults; systemic reactions:
      children 12.8%, adults 11.2% adolescents 7.7%. Females had slightly more AEs.
      Treatment was well tolerated in asthmatic patients (n = 267; GINA I n = 32, II n
      = 104, III n = 17, 114 no classification).In more than 10 years more than 100,000
      patients were treated with high-dose HDM allergoid (1800 PNU) under daily
      practice conditions. Adverse drug reactions (ADRs) were reported in 0.5% of
      patients. 94.6% of these ADRs were expected. Conclusion: SCIT with the marketed
      dose of high-dose HDM allergoid was well tolerated in clinical development and in
      daily practice. There was no increased risk for the investigated patient
      subgroups. Tolerability was comparable to HDM sublingual immunotherapy (SLIT)
      tablets.

PMID- 30294518
TI  - Strategies for the elimination of hepatitis C virus infection as a public health
      threat in the United States.
AB  - Purpose of Review: Direct-acting antiviral regimens for chronic hepatitis C virus
      (HCV) became available in 2014, and these highly curative therapies have the
      potential to reduce HCV-associated morbidity and mortality, decrease
      transmission, and eliminate HCV infection as a public health problem. This review
      summarizes the recommendations by the National Academies of Sciences,
      Engineering, and Medicine for a US strategy for HCV elimination. Recent Findings:
      To achieve proposed targets of reducing HCV incidence by 90% and decreasing HCV
      related mortality by 60% by 2030, there is a critical need to improve HCV
      diagnosis and linkage to care; reduce HCV-related disease by antiviral treatment
      scale-up; reduce HCV incidence; and strengthen HCV surveillance to determine
      achievement of HCV elimination targets over time. Summary: While HCV elimination
      is feasible, success of this national effort will require ongoing collaboration
      and critical resource investment by key stakeholders, including medical and
      public health communities, legislators, community organizers, and patient
      advocates.

PMID- 30294521
TI  - Hybrid control combined with a voluntary biosignal to control a prosthetic hand.
AB  - In this research, the combination of fuzzy/PD and EMG signals, as direct command
      control, is proposed. Although fuzzy/PD strategy was used to control force
      position of the artificial hand, the combination of that with EMG signaling to
      voluntary direct command control is a novel method. In this paper, the EMG signal
      and its role in effective communication between a DC motor with a voltage trigger
      and neurofeedback are initially explained. Moreover, by introducing a filtration
      method, EMG pulses are obtained as stepping pulses with a signal-specific height
      of a voltage between 0 and 6 V, according to EMG domain voltage, with a time
      interval adapted from the EMG stimulus pulses. Two data points from each channel
      of EMG were extracted. The domain of the voltage of the EMG signal is impacted on
      the output of the fuzzy logic unit, and also the time amount between each
      stimulus of the EMG signal is the input of the PD controller. By this method, a
      user can influence grip position and grasping force of his/her prosthesis.

PMID- 30294522
TI  - Intelligence and global health: assessing the role of open source and social
      media intelligence analysis in infectious disease outbreaks.
AB  - Purpose: Open Source Intelligence (OSINT) and Signals Intelligence (SIGINT) from
      the clandestine intelligence sector are being increasingly employed in infectious
      disease outbreaks. The purpose of this article is to explore how such tools might
      be employed in the detection, reporting, and control of outbreaks designated as a
      'threat' by the global community. It is also intended to analyse previous use of
      such tools during the Ebola and SARS epidemics and to discuss key questions
      regarding the ethics and legality of initiatives that further blur the military
      and humanitarian spaces. Methods: We undertake qualitative analysis of current
      discussions on OSINT and SIGINT and their intersection with global health. We
      also review current literature and describe the debates. We built on quantitative
      and qualitative research done into current health collection capabilities.
      Results: This article presents an argument for the use of OSINT in the detection
      of infectious disease outbreaks and how this might occur. Conclusion: We conclude
      that there is a place for OSINT and SIGINT in the detection and reporting of
      outbreaks. However, such tools are not sufficient on their own and must be
      corroborated for the intelligence to be relevant and actionable. Finally, we
      conclude that further discussion on key ethical issues needs to take place before
      such research can continue. In particular, this involves questions of
      jurisdiction, data ownership, and ethical considerations.

PMID- 30294520
TI  - Non-celiac gluten/wheat sensitivity (NCGS)-a currently undefined disorder without
      validated diagnostic criteria and of unknown prevalence: Position statement of
      the task force on food allergy of the German Society of Allergology and Clinical
      Immunology (DGAKI).
AB  - Within the last decade, non-celiac gluten/wheat sensitivity (NCGS) has been
      increasingly discussed not only in the media but also among medical specialties.
      The existence and the possible triggers of NCGS are controversial. Three
      international expert meetings which proposed recommendations for NCGS were not
      independently organized and only partially transparent regarding potential
      conflicts of interest of the participants. The present position statement
      reflects the following aspects about NCGS from an allergist's and nutritionist's
      point of view: (A) Validated diagnostic criteria and/or reliable biomarkers are
      still required. Currently, this condition is frequently self-diagnosed, of
      unknown prevalence and non-validated etiology. (B) Gluten has not been reliably
      identified as an elicitor of NCGS because of high nocebo and placebo effects.
      Double-blind, placebo-controlled provocation tests are of limited value for the
      diagnosis of NCGS and should be performed in a modified manner (changed relation
      of placebo and active substance). (C) Several confounders hamper the assessment
      of subjective symptoms during gluten-reduced or gluten-free diets. Depending on
      the selection of food items, e.g., an increased vegetable intake with soluble
      fibers, diets may induce physiological digestive effects and can modify
      gastrointestinal transit times independent from the avoidance of gluten. (D) A
      gluten-free diet is mandatory in celiac disease based on scientific evidence.
      However, a medically unjustified avoidance of gluten may bear potential
      disadvantages and risks. (E) Due to a lack of diagnostic criteria, a thorough
      differential diagnostic work-up is recommended when NCGS is suspected. This
      includes a careful patient history together with a food-intake and symptom diary,
      if necessary an allergy diagnostic workup and a reliable exclusion of celiac
      disease. We recommend such a structured procedure since a medically proven
      diagnosis is required before considering the avoidance of gluten.

PMID- 30294523
TI  - Using Mindfulness for the Treatment of Insomnia.
AB  - Purpose of review: The goal of this review is to provide an update on the use of
      mindfulness meditation for the treatment of insomnia, including conceptual models
      and empirical evidence from randomized controlled trials. Recent findings: A
      metacognitive model of insomnia has been proposed as a conceptual model to
      explain the application of mindfulness principles for reducing insomnia-related
      arousal. Furthermore, the evidence base for mindfulness-based therapies has grown
      with the results of several randomized controlled trials published in the past
      three years. Treatment effects appear to be strongest on self-report measures
      compared to objective measures of sleep. Summary: Treatment programs featuring
      mindfulness meditation appear to be viable treatment options for people with
      insomnia. Further research is needed to determine who is likely to benefit from
      mindfulness-based therapies and how these interventions work. Additionally,
      further work is needed to resolve issues related to the delivery and
      implementation of mindfulness-based therapies.

PMID- 30294524
TI  - Biologics for the treatment of noninfectious uveitis.

PMID- 30294525
TI  - Recommendation of using systemic anti-tumor necrosis factor-alpha for the
      treatment of noninfectious uveitis in Taiwan.
AB  - Noninfectious uveitis is a sight-threatening disease with an autoimmune or
      autoinflammatory basis. Systemic treatment is required if intraocular
      inflammation threatens a patient's vision or cannot be controlled locally and
      when it is associated with systemic rheumatic diseases. Corticosteroids and
      immunomodulatory chemotherapy are the conventional initial treatments. However,
      the various side effects of these therapies increase the burden on patients, not
      only physically but also mentally. Moreover, uncontrolled inflammation and poor
      visual outcomes have sometimes been recorded despite the combination of these
      medications or their high dosage. Antitumor necrosis factor-alpha (anti-TNF
      alpha) and other biologic agents have been widely used to treat rheumatic
      diseases for >15 years. Randomized controlled clinical trials have demonstrated
      that anti-TNF-alpha can reduce and delay episodes of intraocular inflammation not
      only in patients with active uveitis but also in corticosteroid-dependent
      patients with inactive uveitis. The Taiwan Food and Drug Administration approved
      the use of adalimumab, an anti-TNF-alpha agent, for treating nonanterior
      noninfectious uveitis (NANIU) in 2017. This report provides a recommendation and
      a proposed stepladder approach for using anti-TNF-alpha agents to treat NANIU in
      Taiwan.

PMID- 30294527
TI  - Dexamethasone implant (0.7 mg) in Indian patients with macular edema: Real-life
      scenario.
AB  - Context: Role of Ozurdex in macular edema due to various posterior segment
      pathologies. AIM: The aim of this study is to report outcome of Ozurdex implant
      in macular edema (ME) secondary to various posterior segment pathologies.
      SETTINGS AND DESIGN: This was a single-center, retrospective, interventional
      study. SUBJECTS AND METHODS: Patients of ME were treated with one or more Ozurdex
      implants (0.7 mg). Data collection included demographic details, best-corrected
      visual acuity (BCVA), central foveal thickness (CFT), duration of efficacy, and
      record of adverse events (if any) within 24 weeks. STATISTICAL ANALYSIS USED:
      Paired sample t-test, Stata data analysis, and statistical software, version
      12.1, StataCorp, College Station, TX, USA, were used in the study. RESULTS: One
      hundred and sixteen eyes of 104 patients were studied which had a diagnosis of
      diabetic ME (n = 46), retinal vein occlusion (n = 40), and uveitis (n = 30). The
      average age of patients (mean +/- standard deviation) was 50.2 +/- 21.9 years.
      Baseline mean +/- SD (standard deviation) logMAR BCVA, CFT, and intraocular
      pressure (IOP) were 0.636 +/- 0.4, 527.8 +/- 210.1 MUm, and 15.3 +/- 3.8 mmHg,
      respectively. The reinjection interval was around 12-18 weeks. Ozurdex proved its
      efficacy in improving mean logMAR visual acuity and reduction of CFT from
      baseline till 12 weeks' follow-up period (0.414 +/- 0.5 and 301.5 +/- 278.5,
      respectively; P < 0.05), and after 12 weeks' follow-up, it started worsening
      (0.530 +/- 0.9 and 444.8 +/- 375.2, respectively; P > 0.05). The most common
      reported adverse event was significant rise of IOP (>5 mmHg), with a total of 12
      cases followed by cataract 9 cases. CONCLUSION: Ozurdex implant leads to a
      significant improvement in BCVA and CFT values till 12 weeks, followed by a
      gradual decline for all the pathologies studied together. No new safety concerns
      were observed with the Ozurdex implant. The duration of efficacy was found to be
      <24 weeks.

PMID- 30294528
TI  - Photorefractive keratectomy for correcting residual refractive error following
      cataract surgery with premium intraocular lens implantation.
AB  - PURPOSE: The aim of this study is to evaluate the effectiveness and
      predictability of photorefractive keratectomy (PRK) for correcting residual
      refractive error following cataract surgery with premium intraocular lens (IOL)
      implantation. METHODS: We conducted a retrospective review of the medical records
      of patients who received PRK for correcting residual hyperopia, myopia, and/or
      astigmatism due to unsatisfied uncorrected distance visual acuity (UDVA) after
      cataract extraction with implantation of aspheric, diffractive multifocal, or
      toric IOL from September 2011 to December 2017. Pre-cataract surgery, pre- and
      post-PRK data including UDVA, best-corrected distance visual acuity, and
      refractive status were analyzed. RESULTS: A total of 18 consecutive eyes in 17
      patients were included in this study. The UDVA after PRK improved 1 line or more
      in 10 eyes, remained unchanged in five eyes, and decreased in three eyes. The
      overall improvement in the logarithm of minimal angle of resolution (logMAR) UDVA
      after PRK was significant (P < 0.05). While dividing patients into subgroups
      based on IOL type, significant improvement in logMAR UDVA was found in patients
      with aspheric IOL or diffractive multifocal IOL implantation (P < 0.05). No
      significant improvement of UDVA was found in patients with toric IOL
      implantation. All eyes achieved +/- 1.00 D of the attempted spherical correction,
      demonstrating good predictability of PRK. CONCLUSIONS: PRK was a safe and
      effective procedure to correct residual refractive error following cataract
      extraction with premium IOL implantation. Although satisfactory for all patients,
      the outcome is better and more predictable in patients with aspheric and
      diffractive multifocal IOL implantation and is less satisfactory and
      unpredictable in patients with toric IOL implantation.

PMID- 30294526
TI  - Correction of presbyopia: An integrated update for the practical surgeon.
AB  - Presbyopia results from loss or insufficiency of the eye's accommodative ability,
      and clinically manifests as the inability to focus near objects on the retina. It
      is one of the most common causes of visual impairment worldwide especially in
      adults of productive or working age. Various means of compensating for the loss
      of accommodative ability have been devised from optical tools such as spectacles
      and contact lenses, to topical medications and to surgical procedures. A
      comprehensive search on journal articles about topical and surgical correction of
      presbyopia was undertaken. The various techniques for presbyopia correction, as
      enumerated in these articles, are discussed in this paper with the addition of
      our personal experience and perspective on the future of these techniques.

PMID- 30294529
TI  - Ultra-widefield angiography in the diagnosis and management of uveitis.
AB  - PURPOSE: The aim of this study is to evaluate the clinical use of ultra-widefield
      angiography (UWFA) in uveitis. MATERIALS AND METHODS: We showed the UWFA and
      traditional 55 degrees  fluorescein angiography (FA) of four cases with Eales'
      disease, idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome,
      Behcet's disease, and idiopathic panuveitis in a tertiary medical center.
      Comparison of UWFA with traditional 55 degrees FA in the diagnosis and management
      of uveitis and review of the literature is also presented. RESULTS: Ultra
      widefield FA revealed far-peripheral vascular imaging. This information would not
      have been easily obtained from traditional FA. With more information of the
      peripheral retina, it may facilitate appropriate diagnosis and monitoring, and
      the management may be revised. CONCLUSION: University of Western Australia played
      an important role to confirm the diagnosis of uveitis and to determine the
      corresponding treatment.

PMID- 30294530
TI  - The rescue effect of adalimumab in the treatment of refractory pediatric
      panuveitis complicated with steroid-induced glaucoma.
AB  - We report the rescue effects of adalimumab (HUMIRA(r)) therapy in a case of
      refractory pediatric panuveitis complicated with steroid-induced glaucoma. A 13
      year-old girl had suffered from blurred vision since January 2013. Bilateral
      idiopathic panuveitis with macular edema (ME) was diagnosed. She had previously
      been treated with systemic steroids, methotrexate, cyclosporine, and
      mycophenolate. All treatments had failed to suppress the ocular inflammation and
      ME persisted. Intravitreal dexamethasone implant injections were given to both
      eyes and ME subsided; however, complications with steroid-induced glaucoma and
      cataract occurred. ME also recurred following absorbance of the dexamethasone
      implant. After administration of subcutaneous adalimumab injections every 2
      weeks, inflammatory activity was well controlled and ME subsided.
      Phacoemulsification and posterior intraocular lens implantation were performed in
      both eyes. Menorrhagia and anemia were noted 9 months after adalimumab treatment.
      Thereafter, adalimumab was reduced and her anemia improved. Her vision had
      remained 20/20 for 33 months. Refractory pediatric uveitis usually requires more
      aggressive treatment. Intraocular glucocorticoid releasing implant could be used
      to lessen the possible systemic side effects in children. Intravitreal
      dexamethasone implant was effective in treating the inflammatory ME but could be
      complicated with steroid glaucoma and cataract. Tumor necrosis factor-blocking
      agents have been used to treat chronic, refractory uveitis in adults as well as
      children. Adalimumab was a favorable biological agent in steroid-responding
      pediatric patient of refractory noninfectious uveitis but could be complicated
      with menorrhagia. Long-term follow-up and more cases are mandatory.

PMID- 30294531
TI  - Interferon-alpha2a treatment for refractory Behcet's disease.
AB  - We report a young male patient with Behcet's disease who suffered from sight
      threatening recurrences under treatment with azathioprine, cyclosporine, and
      prednisolone. His uveitis responded well to antitumor necrosis factor (TNF)-alpha
      (adalimumab) for 5 months subsequently. Severe uveitis recurred soon after
      discontinuation of anti-TNF alpha therapy and could not be controlled well with
      reinstitution of the anti-TNF alpha therapy. Interferon-alpha2a (IFN-alpha2a) was
      then given along with low-dose oral prednisone (10 mg/day), and the uveitis
      responded well to this therapy. We continued a maintenance dose with of IFN
      alpha2a three times/week for 2 years. Sight-threatening uveitis did not recur
      under IFN-alpha2a therapy, and the visual acuity improved from "counting fingers"
      to 20/100 in the right eye, while remaining stable with 20/20 vision in the left
      eye. The patient had flu-like symptoms, fever, and severe depression during IFN
      therapy, but an attempt to discontinue INF led to relapse within 1 month. This
      case report suggests that IFN-alpha2a could be an option for treatment in
      Behcet's uveitis. Further study is needed to clarify the efficacy and appropriate
      strategy for IFN-alpha2a therapy for Behcet's uveitis in Taiwan.

PMID- 30294532
TI  - Bilateral anterior uveitis after immunotherapy for malignant melanoma.
AB  - Immune checkpoint blockade therapy is relatively a new treatment for cancer which
      has shown promising results. However, immune-related side effects including
      uveitis have occasionally been reported during this therapy. Herein, we report
      the case of a 65-year-old male who suffered bilateral anterior uveitis after
      immune checkpoint blockade therapy with pembrolizumab and ipilimumab for
      malignant melanoma. His symptoms and signs improved after topical treatment with
      corticosteroids. Clinicians should be aware that uveitis can be an immune-related
      adverse event of immunotherapy.

PMID- 30294533
TI  - Acute syphilitic posterior placoid chorioretinopathy mimicking central serous
      chorioretinopathy: A case report.
AB  - A 51-year-old man had experienced declining visual acuity for 4 months. His best
      corrected visual acuity was 20/40 in both eyes. Ophthalmoscopic examination
      showed a yellowish placoid lesion over the macular area, and spectral-domain
      optical coherence tomography (SD-OCT) revealed subretinal fluid accumulation in
      the left eye, which resembled that seen with central serous chorioretinopathy
      (CSCR). Three days later, fluorescein angiography (FA) revealed fluorescein
      leakage, and indocyanine green angiography (ICGA) showed hypofluorescence over
      the lesion. Persistent ellipsoid zone loss as spontaneously resolved subretinal
      fluid was noted at the same time with SD-OCT. Laboratory examination disclosed
      positive rapid plasma reagin and Treponema pallidum particle agglutination tests
      (titer >1:1280), which confirmed the diagnosis of ocular syphilis. Acute
      syphilitic posterior placoid chorioretinopathy (ASPPC) could mimic CSCR with
      spontaneously resolved subretinal fluid observed in SD-OCT images. The acute loss
      of the ellipsoid zone, mismatched results from SD-OCT and FA, and picture of
      retinitis can also provide hints for differentiating the two diseases.

PMID- 30294534
TI  - Blastoschizomyces capitatus pneumonia in a patient with untreated chronic
      lymphocytic leukemia.
AB  - Several cases have been reported of B. capitatus infections in immunocompromised
      patients. Acute leukemia is the main predisposing factor. Chronic lymphocytic
      leukemia (CLL) is not usually associated with opportunistic infections. We report
      a case of pulmonary infection by B. capitatus in a patient with untreated chronic
      lymphocytic leukemia. Although the patient had a complete recovery, we believe
      that this report will alert clinicians to consider B. capitatus as possible cause
      of severe pneumonia in untreated CLL.

PMID- 30294535
TI  - Invasive rhinocerebral mucormycosis in a patient with liver cirrhosis leading to
      fatal massive stroke.
AB  - Immunocompromised status is associated with invasive fungal infections including
      mucormycosis. These infections are challenging to treat and associated with high
      overall mortality. Here we report a fatal case of invasive mucormycosis in a
      cirrhotic, diabetic patient. Despite the swift diagnosis and management; the
      fungal invasion of the right internal carotid artery lead to massive ischemic
      stroke. Timely diagnosis and management is crucial for management but it seems
      not always enough and new approaches for treatment must be sought.

PMID- 30294536
TI  - Dynamics of ecosystem services provided by subtropical forests in Southeast China
      during succession as measured by donor and receiver value.
AB  - The trends in the provision of ecosystem services during restoration and
      succession of subtropical forests and plantations were quantified, in terms of
      both receiver and donor values, based on a case study of a 3-step secondary
      succession series that included a 400-year-old subtropical forest and a 23-year
      history of growth on 3 subtropical forest plantations in Southeastern China. The
      'People's Republic of China Forestry Standard: Forest Ecosystem Service Valuation
      Norms' was revised and applied to quantify the receiver values of ecosystem
      services, which were then compared with emergy-based, donor values of the
      services. The results revealed that the efficiencies of subtropical forests and
      plantations in providing ecosystem services were 2 orders of magnitude higher
      than similar services provided by the current China economic system, and these
      efficiencies kept increasing over the course of succession. As a result, we
      conclude that afforestation is an efficient way to accelerate both the ability
      and efficiency of subtropical forests to provide ecosystem services. The ability
      of different ecosystems to provide services depends on the concentration of
      available natural resources in the system at a large scale, but also on the
      ability of the ecosystems to capture natural resources in the same or similar
      environments.

PMID- 30294537
TI  - Evaluation of Glypican-3 expression in benign and malignant salivary gland
      tumors.
AB  - Introduction: Glypican-3 (GPC3) is involved in regulation of cell proliferation
      and morphogenesis. It is abundant in embryonic tissue, but limited in most adult
      tissues. GPC3 deletion or mutation can disturb the balance between cell apoptosis
      and proliferation, which may result in tumorigenesis. This study aimed to
      investigate the GPC3 expression in salivary gland tumors (SGTs) and the adjacent
      non-neoplastic tissues. Methods: This study reviewed 50 samples of salivary
      tumors from the archive of Khalili Hospital, Shiraz, Iran, including 17 cases of
      pleomorphic adenoma (PA), 16 cases of mucoepidermoid carcinoma (MEC), and 17
      cases of adenoid cystic carcinoma (ACC); as well as a control group of 23 cases
      of normal salivary gland tissues. GPC3 expression was investigated through
      immunohistochemistry. Results: GPC3 expression was significantly higher in
      malignant tumors (MEC and ACC) than in PA, and higher in PA than in the normal
      salivary glands (P < 0.001). The expression intensity was moderate to strong in
      malignant tumors and weak to moderate in benign tumors. No strong positivity was
      observed in normal salivary gland tissues (P < 0.001). Nor was any association
      detected between the GPC3 expression and intensity with the clinicopathologic
      parameters. Conclusion: Although GPC3 overexpression was observed at the protein
      level in SGTs, and its expression was not related with the clinicopathologic
      factors, the potential use of GPC3 for diagnostic, therapeutic, and prognostic
      purposes requires further investigations.

PMID- 30294539
TI  - A devastating cardiovascular event in an adult cystic fibrosis patient: An
      unforeseen outcome of increasing life expectancy.
AB  - The improving life expectancy for CF is known to be one of the biggest success
      stories in medicine. Life expectancy has increased from 6 months during the early
      20th century to 42.7 years from in 2012-2016. As the life expectancy of CF
      patients has increased, it is important to consider other co-morbidities that
      these patients may encounter, and the impact this may have on their morbidity and
      mortality. We present a case of a 33-year-old male admitted to the hospital for a
      CF exacerbation who had an acute neurological decompensation due to an infarction
      of his right occipital and posterior temporal lobe.

PMID- 30294538
TI  - A clinico-microbiologic study comparing the efficacy of locally delivered
      chlorhexidine chip and diode LASER as an adjunct to non-surgical periodontal
      therapy.
AB  - Background: Considering the microbial etiology of the periodontal disease, the
      periodontal therapy aims to control or abolish the pathogenic microbes. The gold
      standard scaling and root planing procedure has been used since time immemorial
      but the drawbacks associated with it have led to the development of various
      adjunctive means. The current study was therefore, performed to comparatively
      assess the efficacy of local delivery of chlorhexidine and 808-nm diode LASER as
      an appurtenance to scaling and root planing in patients with chronic
      periodontitis. Methods: In a randomized split mouth evaluation, 30 patients
      having probing depth of >=5 mm which bled on probing at least at 3 different
      sites were included. At baseline, the evaluation of plaque index, bleeding index,
      probing pocket depth and clinical attachment level was done and the microbial
      samples were collected for the assessment of spirochetes, motile rods and coccoid
      cells. The 3 selected sites of each subject were allocated to 3 different groups
      A, B, C viz; Scaling and root planing (SRP) + chlorhexidine chip, SRP + diode
      LASER and SRP respectively. The patients were recalled after 4 weeks to re
      evaluate the clinical and microbiological parameters. Results: All the parameters
      significantly reduced from baseline to 4 weeks in all the 3 groups. Intergroup
      comparisons revealed remarkable difference between group A and C and group B and
      C, respectively; no notably significant difference was found between group A and
      B. Conclusion: The additional use of LASER and chlorhexidine chip assures anti
      inflammatory effect and anti-microbial effect that allows reduction in bacterial
      counts and promotes healing. The use of adjuncts have been found to be
      efficacious in controlling disease and promoting periodontal health and thereby
      reducing the need for surgical procedures to be undertaken.

PMID- 30294540
TI  - A simple technique for thoracoscopic assisted placement of the distal limb of
      syringopleural shunts.
AB  - Background: Syringomyelia is an unusual accumulation of fluid within the spinal
      cord that may be associated with significant neurologic symptoms. Surgical
      drainage using various techniques is often required to reduce the
      intraparenchymal pressure and to alleviate symptoms. Syringopleural shunting
      seems to produce best results. Patients and methods: A simple technique to insert
      the distal limb of the syringopleural shunt into the pleural space is described
      in detail. The patient is placed in prone position. The syrinx is accessed from a
      dorsal incision and the proximal limb is inserted into the fluid cavity. The tube
      is tunneled through the subcutaneous space laterally and caudally. A 5mm blunt
      port is inserted lateral to the scapula and advanced under visual control using a
      5mm 30 degrees  camera through the subcutaneous tissue and muscle and at the
      upper border of the 5th rib through the intercostals. With ventilation paused,
      the pleura is penetrated and CO2 is insufflated with a pressure of 8mm mercury.
      Under visual control the distal limb of the shunt is inserted at the pleural
      recessus and the tube is directed cranially. Positive airway pressure is applied
      re-expanding the lung. The trocar is removed from the pleural cavity and the skin
      is closed with subcuticular sutures. Results: The shunt was successfully placed
      in three consecutive cases including one redo case (1 male, 1 female aged 50 and
      51 years with post traumatic syrinx). Postoperative chest x-ray excluded
      pneumothorax and no chest tube was required. Neurologic improvement was achieved
      in both patients. Conclusions: General surgeons should be familiar with this
      simple technique similar to laparoscopic assisted placement of distal
      ventriculoperitoneal shunt catheters into the abdominal cavity.

PMID- 30294541
TI  - Infestation of introduced raccoons (Procyon lotor) with indigenous ixodid ticks
      on the Miura Peninsula, Kanagawa Prefecture, Japan.
AB  - Since the raccoon (Procyon lotor) was introduced to Japan, studies have
      established that they are infested with native Japanese tick species. However,
      the quantity of ticks infesting raccoons is unknown. We conducted a survey of
      ticks on invasive raccoons captured on the Miura Peninsula, Kanagawa Prefecture,
      Japan, from April 2015 through June 2016 to determine the species of ticks and to
      quantify the intensity of tick infestation in order to obtain basal information
      related to the ecology of host-parasite relationships among indigenous tick
      species and an alien mammalian species. We collected and identified 15,931 ticks
      of two genera and six species, namely, Haemaphysalis flava, H. megaspinosa, H.
      longicornis, H. japonica, Ixodes ovatus, and I. tanuki, from 100 out of 115
      raccoons. The dominant tick species was H. flava (96.8%) and individuals were
      mainly adults. Seasonal patterns of infestation intensity of adults and nymphs
      peaked in the autumn and winter and decreasing in the late spring and summer, May
      to August, while larvae peaked in August. Our results indicated that host
      parasite relationships between invasive raccoons and Japanese tick species,
      especially H. flava, were established in Kanagawa Prefecture. The ticks infest
      invasive raccoons for their blood-meal and also for overwintering. The results of
      this study extend our understanding of the ecology of tick-borne diseases.

PMID- 30294543
TI  - Stroke-like episodes in coenzyme-Q deficiency may respond to NO-precursors and
      non-mitochondrion-toxic antiepileptic drugs.

PMID- 30294542
TI  - The double-stage delay-multiply-and-sum image reconstruction method improves
      imaging quality in a LED-based photoacoustic array scanner.
AB  - Light-emitting diode-based photoacoustic imaging is more compact and affordable
      than laser-based systems, but it has low power and hence a high number of
      replicates. Here, we describe double-stage delay-multiply-and-sum (DS-DMAS) to
      improve image quality collected on a LED-based scanner. DS-DMAS was evaluated
      experimentally using point targets (in different laterals and depths) as well as
      a hair and a rabbit eye. This algorithm can compensate for the low SNR of LED
      based systems and offer better lateral resolution of about 60%, 25%, higher
      contrast ratio of about 97%, 34%, and better full-width-half-maximum of about
      60%, 25%, versus delay-and-sum) and delay-multiply-and-sum, respectively. More
      importantly, DS-DMAS offers this using a smaller number of frames (only 2% of all
      the frames). These results indicate that DS-DMAS might be a valuable tool in the
      translation of LED-based and other low power PAI systems.

PMID- 30294544
TI  - Cytokines levels in late-diagnosed Classical Homocystinuria patients.

PMID- 30294545
TI  - Antiepileptic treatment may determine the outcome of FARS2 mutation carriers.

PMID- 30294547
TI  - Transperitoneal laparoscopic nephrectomy for giant hydronephrotic non-functioning
      kidney.

PMID- 30294546
TI  - The first pediatric case of glucagon receptor defect due to biallelic mutations
      in GCGR is identified by newborn screening of elevated arginine.
AB  - Glucagon receptor (GCGR) defect (Mahvash disease) is an autosomal recessive
      hereditary pancreatic neuroendocrine tumor (PNET) syndrome that has only been
      reported in adults with pancreatic alpha cell hyperplasia and PNETs. We describe
      a 7-year-old girl with persistent hyperaminoacidemia, notable for elevations of
      glutamine (normal ammonia), alanine (normal lactate), dibasic amino acids
      (arginine, lysine and ornithine), threonine and serine. She initially was brought
      to medical attention by an elevated arginine on newborn screening (NBS) and
      treated for presumed arginase deficiency with a low protein diet, essential amino
      acids formula and an ammonia scavenger drug. This treatment normalized plasma
      amino acids. She had intermittent emesis and anorexia, but was intellectually
      normal. Arginase enzyme assay and ARG1 sequencing and deletion/duplication
      analysis were normal. Treatments were stopped, but similar pattern of
      hyperaminoacidemia recurred. She also had hypercholesterolemia type IIa, with
      only elevated LDL cholesterol, despite an extremely lean body habitus. Exome
      sequencing was initially non-diagnostic. Through a literature search, we
      recognized the pattern of hyperaminoacidemia was strikingly similar to that
      reported in the Gcgr -/- knockout mice. Subsequently the patient was found to
      have an extremely elevated plasma glucagon and a novel, homozygous c.958_960del
      (p.Phe320del) variant in GCGR. Functional studies confirmed the pathogenicity of
      this variant. This case expands the clinical phenotype of GCGR defect in children
      and emphasizes the clinical utility of plasma amino acids in screening, diagnosis
      and monitoring glucagon signaling interruption. Early identification of a GCGR
      defect may provide an opportunity for potential beneficial treatment for an adult
      onset tumor predisposition disease.

PMID- 30294548
TI  - A rare case of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome with solitary
      ectopic pelvic kidney and uretropelvic junction (UPJ) obstruction.

PMID- 30294549
TI  - Primary angiosarcoma of the testis with retroperitoneal metastasis.

PMID- 30294550
TI  - Transplanting a horseshoe kidney: A case report and review of surgical
      strategies.

PMID- 30294551
TI  - Human urinary myiasis by Psychoda albipennis: A case report and review of
      literature.

PMID- 30294552
TI  - Attitudes and habits of patients with type 1 diabetes during fasting Ramadan.
AB  - Objective: Fasting Ramadan is associated with changes in lifestyle patterns of
      patients with diabetes who choose to perform fasting. We aimed to determine the
      attitude and habits of patients with type 1 diabetes during fasting Ramadan.
      Methods: The study comprised a prospective cohort of patients with type 1
      diabetes who were on insulin pump or multiple daily insulin injections (MDI)
      regimen. Patient questionnaires included the frequency of self-monitoring of
      blood glucose (SMBG), the need to make changes in insulin regimen by patients,
      timings of insulin administration, performing carbohydrate counting and levels of
      physical activity. Results: A total of 156 patients were studied (61 patients on
      insulin pump and 95 patients on MDI). Patients on pump therapy performed SMBG
      more frequently than those on MDI regimen (4.8 +/- 1.4 and 3.7 +/- 1.7 times per
      day, respectively, P = 0.001) and were more likely to perform carbohydrate
      counting (32.7% and 8.4% of pump and MDI patients, respectively, P < 0.001).
      There was no difference in the percentage of patients who made changes in insulin
      doses (74.5% of the pump group and 77.3% of MDI patients) or those who had any
      level of physical activity (12.5% of the pump group and 21.1% of the MDI group).
      The timing of administering meal insulin in relation to sunset meal was variable
      with a preference to taking the injection immediately at sunset. There was no
      difference in glucose control between both groups as measured by frucotsamine
      levels or the number of days that patients have to stop fasting. Conclusion:
      Fasting Ramadan is associated with significant and variable changes in the
      attitude and behaviors of patients with type 1 diabetes with no difference in
      glucose control between patients on insulin pump or MDI regimen. Further studies
      are needed to define the role of education and its effect on these attitudes and
      patient care in this population.ClinicalTrials.gov Identifier: NCT01941238.

PMID- 30294553
TI  - Less known aspects of central hypothyroidism: Part 2 - Congenital etiologies.
AB  - Central hypothyroidism (CH) occurs approximately in 1:50,000, and therefore is
      expected to be one thousand times rarer compared with primary hypothyroidism.
      Despite its rarity in the general population, it is much more common in certain
      disorders, in which it is frequently associated with other pituitary hormone
      deficiencies. The aim of this paper is to provide an updated review on the
      frequency of congenital CH, which is <1:50,000, and on its etiology, disregarding
      CH caused by other genetic defects, such as mutations of transcription factors
      involved in pituitary organogenesis or mutations of the genes encoding TRH or TRH
      receptor.

PMID- 30294555
TI  - KALGAETM (Klebsormidium flaccidum var. ZIVO) dried algal biomass - 90-day dietary
      toxicity study and genotoxicity studies.
AB  - Consumers are demanding plant-based alternative protein sources to complement
      traditional animal-based protein sources to fulfill their dietary protein
      requirements. KALGAETM, a dried algal biomass derived from Klebsormidium
      flaccidum var. ZIVO, is a potential source of plant-based protein that has been
      evaluated for safety to support its use as a food ingredient. There were no
      treatment-related adverse effects observed in the 14-day palatability/toxicity or
      90-day dietary toxicity study in CRL Sprague-Dawley CD(r) IGS rats. In the 90-day
      study, KALGAETM was administered to rats in the diet at 0, 37,500, 75,000, or
      150,000 ppm. No adverse effects were attributed to the test substance for the
      following parameters: body weight, body weight gain, mean food consumption and
      efficiency, hematology, clinical chemistry, urinalysis, gross pathology,
      histopathology, or organ weights. Although some statistically significant effects
      were recorded, the effects were not considered to be of toxicological relevance.
      A No Observable Adverse Effect Level (NOAEL) of 150,000 ppm, equivalent to
      dietary intakes of 7895.2 (male) and 9708.09 (female) mg KALGAETM/kg body
      weight/day in rats was established. KALGAETM was non-mutagenic in the in vitro
      bacterial reverse mutation assay at concentrations up to 5000 MUg/plate (with or
      without S9 metabolic activation), nor was KALGAETM genotoxic in the in vivo
      mammalian erythrocyte micronucleus test in Swiss albino (ICR) mice. These results
      support the safe use of KALGAETM as an ingredient in foods.

PMID- 30294554
TI  - Therapeutic activity of sour orange albedo extract and abundant flavanones loaded
      silica nanoparticles against acrylamide-induced hepatotoxicity.
AB  - The current research aims to demonstrate the therapeutic effect of sour orange
      albedo extract (SOAE) and two flavanones loaded-tetraethylorthosilicate (TEOS)
      using sol-gel technique, in adose100 mg/kg body weight taken orally or45 days
      against acrylamide (ACR)toxicity in rats. This was achieved through measuring the
      activities of specific biochemical parameters related to liver functions in
      tissue of ACR intoxicated rats as compared to normal one. Liver functions
      included alanine and aspartate aminotransferases, antioxidants and oxidative
      stress biomarkers; superoxide dismutase, catalase, glutathione and lipid peroxide
      (malondialdehyde, MDA). Moreover, histological examination of liver was performed
      to confirm the biochemical findings. The present results clearly indicated
      disturbances in all biochemical parameters, such as increase in the liver
      function enzyme activities and MDA level. Results of ATPase enzyme activities
      revealed significant decrease in ACR intoxicated rats and liver biomarker enzymes
      declared significant decrease. On the other hand, treatment of intoxicated rats
      with the previous different nano-particles natural product demonstrated
      improvement in all biochemical parameters under investigation.

PMID- 30294556
TI  - Endophytic Fusarium solani: A rich source of cytotoxic and antimicrobial
      napthaquinone and aza-anthraquinone derivatives.
AB  - This study reports the chemical investigation and bioactivity of the secondary
      metabolites produced by the endophytic fungus Fusarium solani isolated from
      Cassia alata Linn. growing in Bangladesh. This plant was collected from
      conservation forest in Bangladesh and belongs to the Caesalpiniaceae family. The
      endophytic fungus Fusarium solani was isolated from the tissue of root of this
      plant. The fungal strain was identified by morphological characters and DNA
      sequencing. The crude organic extract of the fungal strain was proven to be
      active when tested for cytotoxicity against Brine Shrimp Lethality Bioassay,
      antimicrobial and antioxidant activity. The bioactivity guided fractionation of
      the ethyl acetate extract leads to the isolation of seven secondary metabolites
      in pure form. The structures of the isolated compounds were determined by the
      analysis of NMR and mass spectroscopic data. Bioassay investigation of the
      isolated secondary metabolites suggested aza-anthraquinones are more potent
      bioactive compounds as anticancer and antimicrobial agent.

PMID- 30294557
TI  - Fetal hyperthyroidism associated with maternal thyroid autoantibodies: A case
      report.
AB  - A 33-year-old Caucasian woman was referred at 24 + 3 weeks of gestation due to
      fetal tachycardia and hydrops. She had an uncomplicated pregnancy 16 years
      previously and was on levothyroxine after total thyroidectomy for Graves' disease
      6 years previously, when she developed moderate exophthalmos. Laboratory
      evaluation revealed appropriate thyroid function for this time of gestation:
      thyroid stimulating hormone (TSH) 1.7 MUU/ml (1-3), fT4 18.53 pmol/l (12-22),
      with positive antibodies: anti-TPO 157 U/ml (<35), TSH receptor antibodies (TRAb)
      171.95 U/l (<1.75). The diagnosis was fetal hyperthyroidism due to transplacental
      passage of stimulating maternal TRAb. Methimazole and digoxin were initiated. The
      patient remained euthyroid, with fT4 levels in the upper normal range. The fetus
      showed intrauterine growth retardation, oligohydramnios, aggravating hydrops,
      goiter with increased central vascularization and improved heart rate without
      signs of cardiac failure. At 30 + 3 weeks a hydropic hyperthyroid male newborn
      (birthweight 1560 g) was delivered by cesarean section and admitted to the
      neonatal intensive care unit. Cord serum showed neonatal hyperthyroidism.
      Methimazole and propranolol were administered to the newborn. On the 5th
      postnatal day the infant died because of severe infection inducing respiratory
      dysfunction, hemodynamic deterioration and cardiac asystole. Graves' disease
      occurs in about 0.2% of pregnancies. Hyperthyroidism occurs in 1-5% of neonates
      born to mothers with Graves' disease and the risk correlates with the maternal
      TRAb titer. Early diagnosis and treatment are crucial not only in pregnant women
      with active disease, but also in mothers with a history of Graves' disease, even
      after definitive treatment such as thyroidectomy or ablative therapy.

PMID- 30294558
TI  - Standard method for microCT-based additive manufacturing quality control 3:
      Surface roughness.
AB  - The use of microCT of 10 mm coupon samples produced by AM has the potential to
      provide useful information of mean density and detailed porosity information of
      the interior of the samples. In addition, the same scan data can be used to
      provide surface roughness analysis of the as-built surfaces of the same coupon
      samples. This can be used to compare process parameters or new materials. While
      surface roughness is traditionally done using tactile probes or with non-contact
      interferometric techniques, the complex surfaces in AM are sometimes difficult to
      access and may be very rough, with undercuts and may be difficult to accurately
      measure using traditional techniques which are meant for smoother surfaces. This
      standard workflow demonstrates on a coupon sample how to acquire surface
      roughness results, and compares the results from roughly the same area of the
      same sample with tactile probe results. The same principle can be applied to more
      complex parts, keeping in mind the resolution limit vs sample size of microCT.

PMID- 30294559
TI  - Standard method for microCT-based additive manufacturing quality control 2:
      Density measurement.
AB  - MicroCT is best known for its ability to detect and quantify porosity or defects,
      and to visualize its 3D distribution. However, it is also possible to obtain
      accurate volumetric measurements from parts - this can be used in combination
      with the part mass to provide a good measure of its average density. The
      advantage of this density-measurement method is the ability to combine the
      density measurement with visualization and other microCT analyses of the same
      sample. These other analyses may include detailed porosity or void analysis (size
      and distribution) and roughness assessment, obtainable with the same scan data.
      Simple imaging of the interior of the sample allows the detection of
      unconsolidated powder, open porosity to the surface or the presence of
      inclusions. The CT density method presented here makes use of a 10 mm cube sample
      and a simple data analysis workflow, facilitating standardization of the method.
      A laboratory microCT scanner is required at 15 MUm voxel size, suitable software
      to allow sub-voxel precise edge determination of the scanned sample and hence an
      accurate total volume measurement, and a scale with accuracy to 3 digits.
      *MicroCT-based mean density measurement method.*Accurate volume measurement and
      scale mass.*10 mm cube sample allows standardization and automation of workflow.

PMID- 30294560
TI  - Analytical methods for determination of bisphenol A, 4-tert-octylphenol and 4
      nonylphenol in herrings and physiological fluids of the grey seal.
AB  - *The aim of this work was to develop the methods of determination for phenol
      derivatives: bisphenol A (BPA), 4-tert-octylphenol (OP) and 4-nonylphenol (NP),
      in the whole body of herring Clupea harengus and in physiological fluids of the
      Baltic grey seal Halichoerus grypus grypus (blood and milk).*Methods were based
      on liquid chromatography coupled with a fluorescence detector (HPLC-FL).*These
      methods were satisfactorily validated, each showing good recovery (>80%) and
      precision (RSD < 15%). Regarding the limit of quantification (LOQ), this was
      established at <2 ng g-1 for herring, <0.07 ng cm-3 for blood and <0.1 ng cm-3
      for milk.

PMID- 30294561
TI  - Isolation and characterization of plumbagin (5- hydroxyl- 2- methylnaptalene-1,4
      dione) producing endophytic fungi Cladosporium delicatulum from endemic medicinal
      plants: Isolation and characterization of plumbagin producing endophytic fungi
      from endemic medicinal plants.
AB  - The rationale of the present study was to isolate and identify endophytic fungi
      from endemic medicinal plants in Eastern Ghats and screened for antimicrobial
      potential of isolated fungal crude extracts. A total of 329 endophytic strains
      were isolated from 600 infected leaves and stem cuttings of endemic plants. The
      diversity and species richness was analyzed statistically and found to be higher
      in leaf segments than in stem segments. From isolated fungal strains,
      Cladosporium delicatulum was identified using molecular identification methods
      and selected as the most potent plumbagin-producing endophytic strain. Further
      the isolation and structural characterization of endophytic fungal plumbagin (5
      hydroxyl-2-methylnaptalene-1,4-dione) was purified and confirmed through
      spectroscopy analysis. The molecular weight was determined as m/z 188 in positive
      mode by ESI-MS, which confirmed to be plumbagin which potentially inhibited all
      tested pathogens, therefore the endophytic fungal plumbagin from the current
      study possesses important biological activities against pathogens.

PMID- 30294562
TI  - Pan-Indian Reference Database for the Diagnosis of Osteoporosis: A Need Indeed.

PMID- 30294563
TI  - Influence of Different Reference Databases on Categorization of Bone Mineral
      Density: A Study on Rural Postmenopausal Women from Southern India.
AB  - Background and Objectives: Currently available DXA (Dual energy X-ray
      Absorptiometry) scanners utilise bone mineral density (BMD) of Caucasian
      population to calculate T scores and categorise BMD. We studied the influence of
      various databases on classification of BMD in south-Indian postmenopausal women
      aged above 50 years. Methodology: This was a cross-sectional study. Hologic DXA
      scanner was used to estimate BMD at lumbar spine (LS) and femoral neck (FN). T
      scores of <=-2.5, -2.4 to -1, -0.9 to +1 were diagnostic of osteoporosis,
      osteopenia and normal respectively. Three reference databases(Italian, Korean and
      north Indian) were used to recalculate T scores. The agreement (K=kappa) between
      manufacturer provided database and the other databases was studied. The impact of
      different databases in diagnosing osteoporosis in subjects with FN fracture was
      assessed. Results: A total of 1956 postmenopausal women with mean (SD) age of 62
      (4.3) years and 211 femoral neck(FN) fracture subjects with mean(SD) age of 68
      (7.2) years were recruited. In subjects with fracture, osteoporosis at FN was
      found in 72% with Caucasian, 88% with North Indian, 56% with Italian, and 45%
      with Korean database. On comparing manufacturer provided database with the other
      population-specific reference, there was perfect agreement with north Indian
      (kappa = 0.81 [FN], kappa = 0.82 [LS]) and good agreement with the Italian
      database (kappa = 0.78 [FN], kappa = 0.74 [LS]). Conclusion: North-Indian
      database identified most of the participants with FN fracture as having
      osteoporosis and had perfect agreement with the manufacturer's database. Follow
      up studies will further validate the impact of utilizing this database in
      clinical practice.

PMID- 30294564
TI  - The Effects of Vitamin D Supplementation on Thyroid Function in Hypothyroid
      Patients: A Randomized, Double-blind, Placebo-controlled Trial.
AB  - Background: Data on the effects of vitamin D supplementation on thyroid function
      in hypothyroid patients are scarce. Objective: This study was done to evaluate
      the effects of vitamin D supplementation on thyroid function in hypothyroid
      patients. Material and Methods: This randomized double-blind, placebo-controlled
      trial was conducted on 201 hypothyroid patients aged 20-60 years old. Subjects
      were randomly assigned into two groups to intake either 50,000 IU vitamin D
      supplements (n = 102) or placebo (n = 99) weekly for 12 weeks. Markers of related
      with thyroid function were assessed at first and 12 weeks after the intervention.
      Results: After 12 weeks of intervention, compared to the placebo, vitamin D
      supplementation resulted in significant increases in serum 25-hydroxyvitamin D
      (+26.5 +/- 11.6 vs. 0.0 +/- 0.0 ng/mL, P < 0.001) and calcium (+0.4 +/- 0.7 vs.
      0.1 +/- 0.6 mg/dL, P = 0.002), and a significant decrease in serum thyroid
      stimulating hormone (TSH) levels (-0.4 +/- 0.6 vs. +0.1 +/- 2.0 MUIU/mL, P =
      0.02). A trend towards a greater decrease in serum parathyroid hormone (PTH)
      levels was observed in vitamin D group compared to placebo group (-3.8 vs. +1.9,
      P = 0.07). We did not observe any significant changes in serum T3, T4, alkaline
      phosphatase (ALP) and albumin levels following supplementation of vitamin D
      compared with the placebo. Conclusion: Overall, the current study demonstrated
      that vitamin D supplementation among hypothyroid patients for 12 weeks improved
      serum TSH and calcium concentrations compared with the placebo, but it did not
      alter serum T3, T4, ALP, PTH, and albumin levels.

PMID- 30294565
TI  - Ultrasound Elastography is a Useful Adjunct to Conventional Ultrasonography and
      Needle Aspiration in Preoperative Prediction of Malignancy in Thyroid Nodules: A
      Northern India Perspective.
AB  - Introduction: Data on ultrasound elastography (USE) are scant from India. This
      study aimed to compare the sensitivity and specificity of USE with thyroid
      ultrasonography (USG) and fine-needle aspiration (FNA) as preoperative predictor
      of malignancy, using postoperative histopathology as gold standard. Materials and
      Methods: Consecutive patients with thyroid swelling/goiter underwent thyroid USG
      followed by USE. Patients with pure cystic nodules or eggshell calcification were
      excluded. Patients with nodules >10 mm with one or more high-risk USG features
      underwent FNA. Patients with no USG high-risk features, benign score on USE, and
      benign FNA were conservatively followed. All other patients underwent
      thyroidectomy. Results: 246 consecutive patients underwent USG. Data from 97
      patients (117 nodules) were analyzed. Median age of patients was 43 years with
      85.4% females. All patients with USE score-1 had benign USG and FNA
      characteristics. Of 86 nodules having USE score-2, 18.6% nodules were hypoechoic
      and 16.28% had microcalcification. Hypoechogenicity and microcalcifications were
      observed in 66.67% nodules with USE score-3. All nodules with USE score-4 and 5
      were hypoechoic and had microcalcifications. Histopathology was benign in 84 and
      malignant in 33 patients. Occurrence of malignancy in USE scores 1-5 was 0, 4.65,
      100, 90.5, and 100%, respectively. All eight nodules with diagnosis of follicular
      adenoma had preoperative USE score-2. The sensitivity of preoperative USG, USE,
      and FNA in picking up malignancy was 66.67, 87.88, and 69.70%, respectively.
      Specificity of USG, USE, and FNA in detecting thyroid malignancy was 88.10, 100,
      and 97.6%, respectively. False positivity rates for USG, USE, and FNA in
      diagnosing thyroid malignancy was 11.9, 0, and 2.4%, respectively. The overall
      diagnostic accuracy of USG, USE, and FNA cytology in this study was 82.05, 96.58,
      and 89.74%, respectively. Conclusion: USE may be better than USG for preoperative
      detection of malignancy in thyroid nodules.

PMID- 30294566
TI  - Ultrasound-guided Fine-needle Aspiration Cytology along with Clinical and
      Radiological Features in Predicting Thyroid Malignancy in Nodules >=1 cm.
AB  - Aims and Objectives: The aim of the study is to examine the adequacy and accuracy
      of ultrasound-guided fine-needle aspiration cytology (US-FNAC) in thyroid nodules
      >=1 cm and to analyze the clinical, sonological, and cytological features in
      predicting thyroid malignancy. Materials and Methods: US-FNAC was done on 290
      patients from December 2013 to December 2014 by the radiologist. The Thyroid
      Imaging Reporting and Data System (TIRADS) was used to record the sonological
      features. FNAC samples were reported by a dedicated cytopathologist. Accuracy was
      calculated by comparing US-FNAC, clinical features and ultrasound (US) features
      for those who had final histopathology till April 2017. Results: The adequacy of
      US-FNAC in this study was 80.2%. Thyroidectomy was performed in 128/290 (44.1%).
      The sensitivity and specificity of US-FNAC in this study is 83.9 and 76.3%,
      respectively, with a positive predictive value of 85.2%, negative predictive
      value of 74.4%, and an accuracy of 81% in predicting malignancy in thyroid
      nodules >=1 cm. The malignancy rate in benign FNAC sample was 25% (10/40), and
      was 69% (8/13) in those with a follicular lesion of undetermined significance
      (FLUS). Around 80% of benign and 89% of FLUS had follicular variant of papillary
      carcinoma of thyroid (FVPTC). US-FNAC, a high TIRADS score, and US features such
      as marked hypoechogenicity, taller than wide, irregular margins,
      microcalcification, and clinical features, such as hard in consistency and
      significant cervical lymph nodes, were important in predicting malignancy (P <
      0.001). Conclusions: The accuracy of US-FNAC in this study is 81%. The US-FNAC, a
      high TIRADS score, a hard thyroid nodule, and significant cervical lymph nodes
      are important in predicting malignancy. The accuracy rate in benign and atypia
      undetermined significance categories needs to improve in this study. Further
      research to help in decreasing false negative rates of FVPTC will help in
      increasing the accuracy of US-FNAC in the present study.

PMID- 30294567
TI  - Study of Pituitary Morphometry Using MRI in Indian Subjects.
AB  - Aim: To establish normative measurements of pituitary gland in Indian population.
      Material and Methods: In this cross-sectional study, we measured dimensions of
      pituitary gland in 482 (213 females and 269 males) Indian subjects with
      apparently normal pituitary gland function. Mid-sagittal T1-weighted image (T1
      WI) on magnetic resonance imaging (MRI) was used to measure height and length of
      pituitary gland. Pituitary gland width was measured using coronal T1-WI and
      pituitary gland volume was calculated. Results: Mean height, length and
      calculated volume of pituitary gland was significantly higher in females compared
      to males (p = <0.001, P = 0.03 and P = <0.001, respectively) when all age groups
      were combined but pituitary gland width was not statistically different in male
      and female subjects. When subjects were divided into different age groups, except
      for 10-14 years age group where pituitary height was significantly higher in
      females as compared to male, no significant difference was observed between male
      and female in any of the parameters (height, length, width and volume). The mean
      pituitary gland height was 5.80 +/- 1.32 mm and 5.37 +/- 1.25 mm in female and
      male subjects, respectively. Females achieved peak pituitary gland height in 10
      to 14-year age group, while males achieved their peak pituitary gland height in
      15 to 19-year age group. Conclusion: Our study provides age and sex wise
      normative data for pituitary measurements derived from Indian population.

PMID- 30294568
TI  - An observational Prospective Study to Evaluate the Preoperative Risk Factors of
      New-onset Diabetes Mellitus after Renal Transplantation in a Tertiary Care Centre
      in Eastern India.
AB  - Objectives: This study aimed to determine the pre-transplant risk factors as
      independent predictors on the new-onset of diabetes mellitus after renal
      transplants (NODATs). Materials and Methods: A single-centred prospective real
      world observational study of 100 subjects who underwent renal transplantation
      over a period of 2 years. All known patients with diabetes were excluded from the
      study. NODAT was defined according to the American Diabetes Association
      definition. In addition to pre-transplant workup 2 days prior to transplant, post
      transplant follow-up done on weekly basis for 1st month, every 15th day from 1st
      month to 3rd month, monthly from 3rd month to 12th month. Each transplant patient
      followed up for 1 year post-transplant or for 6 months post-development of NODAT,
      whichever was later. All the pre-transplant variables namely body mass index
      (BMI), family history of diabetes mellitus (DM), HbA1c, fasting insulin level,
      fasting c-peptide level, serology for hepatitis B, C, serum magnesium level and
      pre-operative insulin ressistance were further compared between NODAT and non
      NODAT groups at the end of the study to assess their strength of associations.
      Results: Among the 100 subjects included in the study, 24 developed NODAT. Risk
      factors namely age, family history of DM, BMI, hepatitis B and C infection, total
      cholesterol, triglyceride level, pre-operative HbA1c, pre-operative insulin
      resistance and pre-diabetes were significantly higher, whereas beta-cell
      function, ABO compatibility and magnesium levels being significantly lower in
      NODAT cohort. Conclusion: The incidence of NODAT is quite high (24%). Risk of
      development of NODAT was related to traditional as well as novel risk factors.
      Key aspects lies in identifying patients at risk of developing NODAT, using
      traditional risk factors for early diagnosis and introducing interventions on
      modifiable risk factors for prevention and timely intervention.

PMID- 30294569
TI  - Effect of Implementation of ADA/AACE Guidelines on the Management of Hospitalized
      Hyperglycemic Patients Through Training of Residents: A Tertiary Care Center
      Study.
AB  - Background: Hyperglycemia is a common comorbidity in hospitalized patients and
      may add to adverse outcomes. Various associations have issued guidelines for
      optimal management of hyperglycemia in ill patients. This study aims to assess
      the adherence to current guidelines in inpatient setting and the impact of
      educational interventions on the improvement in adherence to guidelines as well
      as its effect on the level of blood sugar control and patient outcomes. Materials
      and Methods: It was a quasi-experimental pretest and posttest study and was done
      in three phases, viz., observation of current practices, intervention in the form
      of educational interventions, and its effect on change in practices and patient
      outcomes. Results: There was statistically significant 22% increase in the use of
      recommended insulin regimens (P = 0.028). The proportion of blood sugars within
      recommended range in the first 48 h, mean daily blood sugars, and the incidence
      of severe hyperglycemia improved in phase 3 vs phase 1 and was statistically
      significant. On comparing the subgroups, viz., those who followed and those who
      did not follow the guidelines, the results of the proportion of blood sugar in
      recommended range and proportions of blood sugar of more than 250 were found to
      be statistically significant. Conclusion: Dedicated educational interventions
      help in improving healthcare practices. According to current guidelines, rapid
      improvement in hyperglycemia and better glycemic control occur with adherence to
      protocol-based management of hyperglycemia.

PMID- 30294570
TI  - Neonatal Glycemic Status of Infants of Diabetic Mothers in a Tertiary Care
      Hospital.
AB  - Background: Diabetes is a common medical complication during pregnancy that
      results in significant neonatal morbidities. In infants of diabetic mothers
      (IDMs), hypoglycemia is a common complication. Objective: To study the neonatal
      hypoglycemia in IDMs in a tertiary care hospital. Settings and Design: A cross
      sectional study was done in postnatal ward in Bangladesh Institute of Research
      and Rehabilitation in Diabetic, Endocrine and Metabolic Disorders from January to
      December 2009. Subjects and Methods: The data of IDMs were collected from
      postnatal ward. All IDMs delivered during this period staying in postnatal ward
      were included in this study. The outcomes were compared between the hypoglycemic
      and normoglycemic IDMs and between gestational diabetes mellitus (GDM) and pre
      GDM in hypoglycemic group using Chi-square test and Fisher's exact test. The data
      analysis was performed with Epi-enfo7 software. Statistical significance was set
      at P < 0.05. Results: A total of 363 IDMs were included in this study.
      Hypoglycemia developed in 38.3% IDMs and 43.2% mothers of hypoglycemic IDMs had
      GDM and 56.8% had pre-GDM. Duration of maternal diabetes (P = 0.04) and large for
      gestational age (P = 0.0001) were associated with hypoglycemia. Multigravidae
      (82.2% vs 68.3%, P = 0.03), prolonged duration of maternal diabetes (45.46 weeks
      vs 3.23 weeks, P = 0.00001), preterm babies (48.1% vs 28.3% P = 0.009), and
      control of diabetes by insulin (81% vs 46.7%, P = 0.001) were more in pre-GDM,
      and statistically significant. About 85% IDMs developed hypoglycemia within 6 h
      of birth (P-value 0.00001) and majority (68%) were at 2 h of age. Forty percent
      of hypoglycemic IDMs from postnatal ward were admitted in special care baby unit.
      Conclusion: Hypoglycemia observed in 38.3% IDMs and developed within 6 h of age
      and maximum were at 2 h. Early recognition and appropriate intervention are
      needed in IDMs.

PMID- 30294571
TI  - Comparison of Efficacy and Safety of Fixed Dose Combination of Rosuvastatin and
      Choline Fenofibrate to Fixed Dose Combination of Rosuvastatin and Fenofibrate in
      Patients of Mixed Dyslipidemia: A Randomized, Open-label, Multicentre Clinical
      Trial in Indian Population.
AB  - Introduction: This study was conducted to evaluate the safety and efficacy of
      fixed-dose combination (FDC) of rosuvastatin and choline fenofibrate in
      comparison to rosuvastatin and fenofibrate FDC among Indian patients of mixed
      dyslipidemia. This would be a first study evaluating FDC of rosuvastatin and
      choline fenofibrate in Indian population. Methods: A multicenter, open-label,
      randomized, active controlled, comparative, parallel-design study was conducted
      at 12 centers spread all across India. Mixed dyslipidemic patients aged 18-70
      years were randomized to FDC of rosuvastatin 10 mg and choline fenofibrate 135 mg
      (RCF group) and FDC of rosuvastatin 10 mg and fenofibrate 160 mg (RF group) once
      daily for approximately 180 days. The primary endpoint of study was percentage
      change in serum triglyceride level at the end of study from baseline. Results: Of
      290 patients screened, 240 patients were enrolled in this study (120 patients in
      each group). At the end of 180 days, there was a significant reduction in
      triglyceride level in both the groups (-37.7% in RCF group and -37.8% reduction
      in RF group; P < 0.0001 for both); however, the difference between both the
      groups was not statistically significant (P = 0.94). Similarly, there was
      significant increase (P < 0.0001 for both) in high-density lipoprotein
      cholesterol (HDL-C) in both groups (+17.8% in RCF group and +14.9% in
      rosuvastatin fenofibrate RF group). Low-density lipoprotein cholesterol (LDL-C),
      very low-LDL (VLDL-C), and total cholesterol were also reduced significantly in
      both groups (P < 0.0001). However, the difference between two groups for increase
      in HDL-C and decrease in LDL-C, VLDL-C, and total cholesterol was not
      significant. Both the treatments were safe and well tolerated. Conclusion:
      Overall, FDC of rosuvastatin and choline fenofibrate is as safe and effective as
      rosuvastatin and fenofibrate combination in Indian patients with mixed
      dyslipidemia with added advantage improved patient compliance as it can be taken
      irrespective of intake of food.

PMID- 30294572
TI  - Effect of Glycemic Variability on Mortality in ICU Settings: A Prospective
      Observational Study.
AB  - Background: Evidence suggests a role of glycemic variability in intensive care
      unit (ICU) mortality. Objective: To assess effect of glycemic variability and
      ICU/in-hospital mortality. Design: Prospective, observational study. Setting: A
      20-bedded medical/surgical ICU in a tertiary care hospital. Patients: Critically
      ill patients requiring life-support measures admitted to the ICU between November
      1, 2015 and December 30, 2016 with hyperglycemia [random blood sugar (RBS) >=200
      mg%] and sequential organ failure assessment (SOFA) scores <=9. Patients were put
      on predefined insulin infusion protocol, multiple glucose values were obtained,
      and mean blood glucose level (MGL) was calculated as their simple arithmetic
      mean. Standard deviation (SD) of MGL and coefficient of variation (CV) of glucose
      (derived as a percentage of SD to mean blood glucose) were then calculated for
      each patient and analyzed for all-cause death during hospitalization period.
      Results: A total of 123 patients having a mean age of 65.12 +/- 16.27 years, mean
      SOFA score of 5.76 +/- 1.76, and mean HbA1c of 6.22 +/- 0.73% were included. MGL
      was 160.65 +/- 24.19 mg/dl, SD 33.32 +/- 15.08 mg/dl, and CV 20.74 +/- 8.43.
      Deceased as compared to survivors had higher MGL (163.76 +/- 24.85 vs 155.62 +/-
      22.43 mg/dl, P = 0.068) and higher glycemic variability (SD 38.92 +/- 14.44 vs
      25.06 +/- 12.27 mg/dl; P < 0.001 and CV 23.69 +/- 7.9 vs 15.98 +/- 6.87; P <
      0.001). Interestingly, more patients having higher CV at lower MGL (85.7%) died
      as compared to those having lower CV at higher MGL (55.6%). Conclusions: High
      glycemic variability is associated with increased ICU/in-hospital mortality.
      Outcome of patients having less glycemic variability even with slight
      hyperglycemia may be better than those having tight glycemic control but higher
      glycemic variability. Insulin protocols need to be in place for management of
      hyperglycemia in critical care setting aiming for adequate glycemic control as
      well as minimizing glycemic variability.

PMID- 30294573
TI  - It is Time to Carpe Diem with Porcine ACTH - A Comparison of Porcine Sequence
      Corticotropin to Tetracosactide Hexaacetate in Testing the Hypothalamic Pituitary
      Adrenal Axis in Healthy Individuals.
AB  - Context: Our literature search revealed that the use of porcine sequence
      corticotropin has not been validated against tetracosactide hexaacetate in a
      healthy population. Aims: To study the efficacy of using porcine sequence
      corticotropin in comparison with tetracosactide hexaacetate in the evaluation of
      hypothalamo pituitary adrenal (HPA) axis. Materials and Methods: Fifteen healthy
      volunteers were enrolled. Serum cortisol was measured at 0 minute in all subjects
      and at 30 and 60 minutes after tetracosactide hexaacetate 250 MUg intravenously.
      Four weeks later, serum cortisol level was measured at 0 minute and at 30 and 60
      minutes following 24 units of porcine sequence corticotropin given
      intramuscularly. Results: Mean serum cortisol values with tetracosactide were
      30.3 (+/-7.83) MUg/dl and 31.27 (+/-7.36) MUg/dl at 30 and 60 minutes,
      respectively. The mean cortisol values with porcine sequence corticotropin were
      26.33 (+/-5.47) MUg/dl and 31.59 (+/-6.40) MUg/dl at 30 and 60 minutes,
      respectively. All subjects had a response qualified as normal or adequate at 30
      minutes itself. Mean peak serum cortisol response was 32.65 (+/-7.76) MUg/dl in
      tetracosactide group and 31.59 (+/-6.4) MUg/dl in porcine sequence corticotropin
      group, and the responses in two groups were comparable (P = 0.686). There were no
      immediate side effects in both groups, with a lower cost of procedure in the
      porcine corticotropin group. Conclusion: Our study established the efficacy of
      porcine sequence corticotropin in testing the adequacy of HPA axis in healthy
      individuals. Our study also revealed that, the intactness of the HPA axis could
      be confirmed as early as 30 minutes in healthy individuals.

PMID- 30294574
TI  - Epicardial Adipose Tissue Thickness and its Corelation with Metabolic Risk
      Parameters in People Living with HIV: A RIMS Study.
AB  - Context: Epicardial fat envelopes the coronary vessel adventitia without fascial
      separation, thus pathologic inflammation in the fat may promote the growth of
      atherosclerotic plaque in coronary arteries in an 'outside-in' fashion.
      Epicardial fat is quantitatively increased in HIV compared to un-infected people.
      Aims: 1. To assess Epicardial Adipose tissue (EAT) by Computed tomography (CT) in
      PLHIV receiving first line ART (antiretroviral therapy) 2. To correlate EAT with
      metabolic risk parameters. Material and Methods: 215 HIV-infected patients aged
      >18 years on first line ART were included in the cross sectional study. EAT
      thickness were measured by CT scan. Metabolic parameters were measured based on
      metabolic syndrome criteria. Statistical Analysis Used: Data analysis was done
      using IBM SPSS version ver. 21. Probability value of less than 0.5 was taken as
      significant. Ethical Issues: The study was carried out after obtaining approval
      from the Institutional Ethical Committee (IEC), Regional Institute of Medical
      Sciences, Imphal. Results: Half of the patients were found to have EAT thickness
      of 8.1-9 mm and 12.6% of cases had EAT of >9 mm. Mean epicardial thickness was
      8.3 mm +/- 0.7 mm for whole population. Triglyceride and high density lipoprotein
      (HDL) were also found to have positive correlation with EAT thickness (rp= 0.364,
      P = 0.04 and rp= 0.343, P = 0.05 respectively). Conclusion: Epicardial adipose
      tissue thickness is increased in PLHIV receiving highly active anti retroviral
      therapy (HAART) and positively co-related with parameters of metabolic syndrome
      such as waist circumference, HDL cholesterol and triglyceride level.

PMID- 30294575
TI  - A Study of Thyroid Dysfunction in Cirrhosis of Liver and Correlation with
      Severity of Liver Disease.
AB  - Introduction: Liver plays an important role in the metabolism of thyroid
      hormones, as it is the most important organ in the peripheral conversion of
      tetraiodothyronine (T4) to triiodothyronine (T3) by Type 1 deiodinase. Materials
      and Methods: This case-control study included 100 decompensated liver cirrhosis
      patients (71 males and 29 females) and 100 apparently healthy controls (71 male
      and 29 female). Serum FT3, FT4, and thyroid-stimulating hormone (TSH) levels were
      measured using electrochemiluminescence immunoassay and analyses between cases
      versus healthy controls (Group 1) and further analyses in subgroups, cirrhosis
      with hepatic encephalopathy (HE) cases (n = 38) versus cirrhosis without HE cases
      (Subgroup 1), cirrhosis survivors (n = 84) versus cirrhosis nonsurvivors
      (Subgroup 2), HE survivors (n = 23) versus HE nonsurvivors (Subgroup 3). Results
      were also analyzed for severity of liver disease according to Child-Turcotte-Pugh
      (CTP) (Class A, B, and C), model for end-stage liver disease (MELD) score, and HE
      grades. Results: Most common etiology was alcohol (46%) and presentation was
      gross ascites (74%). Cirrhosis patients had statistically significant lower level
      of FT3 (P < 0.0001) and FT4 (P < 0.0001) but had higher level of TSH (P < 0.0001)
      compared with the controls. Cirrhosis with HE (n = 38) had significantly lower
      lever of FT3 (P < 0.0001) compared with cirrhosis without HE (n = 62), whereas
      there was no statistically significant difference in FT4 (P < 0.09) and TSH (P <
      0.60) levels. FT3 level significantly low in HE Grade 4 patients compared with HE
      Grade 1 patients (P = 0.0001). In all cirrhotic patients, FT3 and FT4 were
      negatively correlated, but TSH level was positively correlated with total
      leukocyte counts, serum total bilirubin, aspartate transaminase, alanine
      transaminase, globulin, prothrombin time (PT), blood urea, serum creatinine, CTP,
      and MELD score. Overall, the most common abnormality seen was low T3 (low FT3)
      syndrome 41% (41 out of 100) in cases, 50% (19 out of 38) in cirrhosis with HE,
      and 32% (5 out of 16) in Non-survivors cases. Conclusion: The mean FT3 and FT4
      levels were significantly decrease and mean TSH levels were significantly
      increase in liver cirrhosis patients compared to healthy controls. Level of FT3,
      FT4, and TSH also correlate with the severity of liver disease, level of FT3 can
      be used as prognostic marker for liver cirrhosis patients.

PMID- 30294576
TI  - Correlation between Ultrasound-based TIRADS and Bethesda System for Reporting
      Thyroid-cytopathology: 2-year Experience at a Tertiary Care Center in India.
AB  - Background: In recent times, high-resolution ultrasound thyroid imaging has paved
      the way for significant transformation in clinical approach to thyroid nodule.
      There are several risk stratification systems in thyroid imaging, developed with
      an aim, not only to reduce the inter-observer variability but also to establish
      effective communication system. Thyroid image reporting and data system (TIRADS)
      classification system, which is similar to breast imaging reporting and data
      system for breast lesion, is the most useful of all. To our knowledge, there is
      just a handful published research articles available based on Indian population
      in this regard. In this article, we study the thyroid nodules using high
      resolution ultrasound in Indian population and we try to correlate the TIRADS and
      Bethesda system for reporting thyroid cytopathology. Materials and Methods: This
      prospective study includes 184 patients studied over a period of 2 years (April
      2015-April 2017). Patients having thyroid nodule in B-mode ultrasound and are
      scheduled to get a fine-needle aspiration cytology (FNAC) done. Bethesda
      classification of these nodules is tabulated in follow-up period simultaneously.
      By comparing these data, efficacy of TIRADS in differentiating benign from
      malignant nodules are assessed finally using accuracy, positive predictive value
      (PPV), cross-tabulation, and Chi-square tests. Results: Out of the 117 TIRADS 2
      nodules, none turned out to be Bethesda IV or higher, which means none of these
      nodules turned out to be malignant. The risk of malignancy for TIRADS 2, TIRADS
      3, TIRADS 4, and TIRADS 5 was 0, 2.2, 38.5, and 77.8%, respectively. The risk of
      malignancy percentage in our study is similar to those values obtained in other
      prominent studies. Conclusion: The probability of a particular nodule being
      malignant can be effectively inferred from the ultrasound-based TIRADS system
      with a certain level of confidence. Considering our results and other literature
      reviews, it be can be safely assumed that FNAC can be at least deferred in
      patients having TIRADS 2 nodules, which contribute to majority of newly detected
      cases. In our experience, there is a remarkable correlation exists between TIRADS
      ultrasound classification and Bethesda cytology, especially for benign nodules.

PMID- 30294577
TI  - Association of Hypomagnesemia with Hypocalcemia after Thyroidectomy.
AB  - Background: Hypocalcemia is one of the most common acceptable complications in
      postoperative period after thyroidectomy. Hypomagnesemia has been recognized
      after parathyroid surgery, and it has not been studied extensively after
      thyroidectomy. The aim of this study was to estimate magnesium and calcium ion
      levels in patients undergoing thyroidectomy and to evaluate the association of
      hypomagnesemia with hypocalcemia after thyroidectomy. A prospective study was
      conducted in Government Medical College, Calicut, from December 2012 to November
      2013. Materials and Methods: all patients had undergone total/near-total/subtotal
      thyroidectomy. Pre- and postoperative at 24 h and serum calcium and magnesium
      were measured by automate electrolyte analyzer. Clinical findings of hypocalcemia
      were recorded. Statistical analysis was done using SPSS software, version 17.0.
      Unpaired student t-test was used. Pearson Chi-square test or Fisher's exact test
      was used to compare the percentage for categorical variables. Results: In our
      study, 58% of the patients developed hypocalcemia, biochemical and/or symptomatic
      (S. Ca <8.5). About 34% of patients developed hypomagnesemia, biochemical and/or
      symptomatic (S. Mg <1.7). About 30% of patients developed both hypocalcemia and
      hypomagnesemia. About 24% of patients developed symptoms of both hypocalcemia and
      hypomagnesemia. Discussion: Thyroidectomy patients were at a risk of transient
      and permanent hypoparathyroidism because of chances of parathyroid resection
      during operation. Transient hypocalcemia and hypomagnesemia occur frequently
      after total thyroidectomy. It is important to monitor both calcium and magnesium
      levels after total thyroidectomy and to correct deficiencies to facilitate prompt
      resolution of symptoms. Conclusion: There is an association of hypomagnesemia
      with hypocalcemia after thyroidectomy.

PMID- 30294578
TI  - Effect of Physical Activity during Pregnancy on Gestational Diabetes Mellitus.
AB  - Aims: The present study evaluates association between physical activity and
      Gestational Diabetes Mellitus (GDM), for it can be an effective intervention for
      its management. Though physical activity helps maintain glucose homeostasis,
      evidences of GDM risk are less extensive. Therefore, this study also identifies
      its correlation with maternal blood glucose levels. Materials and Methods: A
      prospective case-control study was carried out among pregnant women attending
      regular antenatal clinic at two private hospitals. The study comprised of 100
      cases and 273 matched controls. Data was collected by personal interviews using a
      standard questionnaire. Physical activity was assessed using long form of
      International Physical Activity Questionnaire (IPAQ) reported as Metabolic
      Equivalent-Minutes per week (MET-Minutes/Week). Statistical Package for Social
      Sciences (SPSS) was used for analysis. Results: Results shows high exposure rates
      for low-to-moderate physical activity among cases, across all domains and sub
      activities. The odds of GDM engaged in domestic and gardening activities for
      <2999 MET-minutes per week are 10 times higher than involved for >=3000 MET
      minutes per week (P < 0.001). The study also shows poor or no correlation between
      physical activity during pregnancy and maternal blood glucose levels. Conclusion:
      Despite existence of poor or no relationship with maternal blood glucose levels,
      prolonged sedentary behavior and decreased physical activities, especially
      domestic, are potential risk factors for GDM, a major finding of the study.

PMID- 30294579
TI  - Impact of Glycemic Levels in Type 2 Diabetes on Periodontitis.
AB  - Aim: The aim is to study the effect of glycemic level in Type 2 diabetes and
      cardiovascular risk factors on periodontal health. Materials and Method: Type 2
      diabetic and nondiabetic patients in the age group of 35-80 years (n = 1700) were
      recruited for the study. Periodontal examination included as follows: Probing
      depth, clinical attachment level (CAL), gingival recession, and bleeding on
      probing. Periodontitis was diagnosed based on the CAL levels and diabetes was
      diagnosed based on glycated hemoglobin (HbA1c) levels. Body mass index, total
      cholesterol, triglyceride, and low-density lipoprotein (LDL) were assessed for
      cardiovascular risk. Patients were characterized into two groups as follows:
      diabetic (n = 1235) and nondiabetic (n = 465). Sociodemographic variables
      included were: age, sex, obesity, smoking, duration of diabetes, and
      periodontitis were assessed. SPSS version 20.0.1.0 was used for all the
      statistical assessments. Conclusion: HbA1c and lipid levels were statistically
      significant with the severity of periodontitis (odds ratio [OR] [95% confidence
      interval [CI]: HbA1c 1.34 [1.019-1.21]; Total cholesterol 1.01 [1.03-1.42];
      triglycerides 1.01 [1.01-1.14]; LDL 1.028 [1.08-1.71]). Smoking and obesity were
      also found to be significantly associated with the presence of periodontitis [OR
      (95% CI): smoking 1.35 (1.10-1.67); obesity 1.23 (1.73-2.05)]. The study
      concluded that uncontrolled HbA1c levels and elevated cardiovascular risk factors
      significantly increase the severity of periodontitis in Type 2 diabetes mellitus.

PMID- 30294580
TI  - Serum Uric Acid Levels in Type 2 Diabetes Mellitus: Is There a Linear
      Relationship with Severity of Carotid Atherosclerosis?
AB  - Aims: The aim of this study was to correlate serum uric acid (SUA) levels and
      carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus
      (DM). Settings and Design: This study was a cross-sectional observational study
      on 103 diabetic patients conducted from September 2015 to May 2017. Subjects and
      Methods: We screened 103 patients with type 2 DM between the ages of 30-65 years.
      SUA levels and the CIMT were measured. The patients were divided into quartiles
      based on uric acid level. The CIMT of the quartiles is compared and analyzed.
      Statistical Analysis Used: Chi-squared test, Analysis of Variance, and Pearson's
      correlation. Results: Uric acid levels were positively associated with CIMT (P =
      0.001). The association remained significant after further adjustment for
      potential confounders. Strong correlation was found among them as depicted by
      correlation coefficient (r = 0.779). Conclusions: Carotid atherosclerosis as
      measured by IMT is associated with SUA levels in patients with type 2 DM.

PMID- 30294581
TI  - Serum Amyloid P and Endocrine Markers in a Cohort of Obese Children.
AB  - Objectives: Obesity in children can lead to morbidity and mortality due to
      metabolic and inflammatory comorbidities. Aims: The objective of the study was to
      investigate the alterations in acute inflammatory markers, serum amyloid P (SAP)
      and cortisol, and endocrine markers, leptin and insulin, in obese children.
      Materials and Methods: Serum leptin, insulin, cortisol, and amyloid P
      concentrations were measured in obese (BMI percentile >85, n = 17) and nonobese
      (BMI percentile < 75, n = 20) children using ELISA and Bio-Plex Bead-based assay.
      Statistical Analysis Used: Serum concentrations of analytes were compared between
      normal and obese groups using 2-tailed student's t-test. Results: Mean leptin,
      insulin, and SAP serum concentrations were significantly higher in obese children
      as compared to the controls (97.19 vs. 4.06, P < 0.05; 21.31 vs 3.56, P < 0.05;
      46.77 vs. 17.89, P < 0.05; respectively). No difference was found in mean serum
      cortisol levels of the two groups. However, cortisol values were higher in obese
      subjects compared to the control group (7.89 vs 6.30, P = 0.15). Leptin corelated
      with insulin (r = 0.42, P = 0.043) and cortisol (r = 0.48, P = 0.025) levels in
      the obese group. Furthermore, leptin, insulin, and SAP levels were corelated with
      BMI (r = 0.80, P < 0.000; r = 0.67, P = 0.015, respectively) and body weight (r =
      0.52, P = 0.01; r = 0.52, P = 0.002; r = 0.54, P = 0.01, respectively) in the
      obese group but did not demonstrate a significant relationship in the nonobese
      group. Conclusion: Elevated SAP levels and increase in leptin and insulin
      indicated a preeminent disposition of morbidly obese children to the development
      of low-grade inflammation and metabolic syndrome.

PMID- 30294582
TI  - A Review on Cardiovascular Outcome Studies of Dipeptidyl Peptidase-4 Inhibitors.
AB  - The U.S. Food and Drug Administration issued a guidance for pharmaceutical
      industry defining preapproval and postapproval requirements for the demonstration
      of cardiovascular (CV) safety for all new medications developed for glycemic
      management in type 2 diabetes. However, results published from the studies of
      dipeptidyl peptidase-4 (DPP-4) inhibitors are conflicting with regard to
      different CV endpoints. Upcoming CV outcome studies perhaps will be able to
      provide additional insights related to diabetes management and help to provide
      the answers to some of these concerns. This article provides a brief overview
      regarding how various CV safety evidence of DPP-4 inhibitor evolved over time
      that highlights possible implication in clinical practice and translates them
      into effective diabetes management.

PMID- 30294584
TI  - PHPT Masquerading as Rickets in Children and Presenting with Rare Skeletal
      Manifestations: Report of Three Cases and Review of Literature.
AB  - Primary hyperparathyroidism (PHPT) is an uncommon condition in children and
      adolescents. However, rapid growth spurt during puberty may result in unmasking
      and development of certain skeletal manifestations of PHPT. We present three
      cases of PHPT associated with rare skeletal manifestations of rickets. All three
      patients had radiological evidence of rickets with primary hyperparathyroidism.
      All the three patients had single gland adenoma. Literature is sparse regarding
      reversal of features of rickets following parathyroidectomy. In all three
      patients of our series, there was a complete resolution of bone/joint pain.
      However, in two children only the genu valgum persisted but their growth was
      normal and they had no proximal muscle weakness. In another child multiple
      corrective surgeries were done to correct the deformities.

PMID- 30294585
TI  - Bilateral Femoral Head Avascular Necrosis with Physiological Doses of Steroids.

PMID- 30294586
TI  - Triple Ectopic Thyroid on Pertechnetate Scintigraphy.

PMID- 30294587
TI  - Occurrence of Subacute Thyroiditis following Influenza Vaccination.

PMID- 30294583
TI  - Emotional and Psychological Needs of People with Diabetes.
AB  - Diabetes is a chronic metabolic disorder that impacts physical, social and mental
      including psychological well-being of people living with it. Additionally,
      psychosocial problems that are most common in diabetes patients often result in
      serious negative impact on patient's well-being and social life, if left un
      addressed. Addressing such psychosocial aspects including cognitive, emotional,
      behavioral and social factors in the treatment interventions would help overcome
      the psychological barriers, associated with adherence and self-care for diabetes;
      the latter being the ultimate goal of management of patients with diabetes. While
      ample literature on self-management and psychological interventions for diabetes
      is available, there is limited information on the impact of psychological
      response and unmanaged emotional distresses on overall health. The current review
      therefore examines the emotional, psychological needs of the patients with
      diabetes and emphasizes the role of diabetologist, mental health professionals
      including clinical psychologists to mitigate the problems faced by these
      patients. Search was performed using a combination of keywords that cover all
      relevant terminology for diabetes and associated emotional distress. The
      psychological reactions experienced by the patient upon diagnosis of diabetes
      have been reviewed in this article with a focus on typical emotional distress at
      different levels. Identifying and supporting patients with psychosocial problems
      early in the course of diabetes may promote psychosocial well-being and improve
      their ability to adjust or take adequate responsibility in diabetes self
      management - the utopian state dreamt of by all diabetologists !.

PMID- 30294588
TI  - Vitamin D Deficiency in Children: Is There a Need for Routine Supplementation?

PMID- 30294589
TI  - Multiple impacted Permanent Teeth-An Indicator for Early Detection of
      Hypoparathyroidism: A Rare Case Report.

PMID- 30294590
TI  - Detection of the MYD88 p.L265P Mutation in the CSF of a Patient With Secondary
      Central Nervous System Lymphoma.
AB  - Primary Central Nervous System Lymphoma (PCNSL) and Metastatic (or Secondary)
      Central Nervous System Lymphoma (MCNSL) are rare central nervous system (CNS)
      malignancies that exhibit aggressive clinical behavior and have a poor prognosis.
      The majority of CNS lymphomas are histologically classified as diffuse large-B
      cell lymphoma (DLBCL). DLBCL harbors a high frequency of mutations in MYD88 and
      CD79b. The MYD88 p.L265P mutation occurs at high frequency in CNS lymphoma and is
      extremely rare in non-hematologic malignancies. Currently, brain biopsy is
      considered the gold standard for CNS lymphoma diagnosis. However, brain biopsy is
      invasive, carries a risk of complications, and can delay initiation of systemic
      therapy. Circulating tumor DNA (ctDNA) in the cerebrospinal fluid (CSF) can be
      utilized to detect tumor-derived mutations. Testing of CSF-ctDNA is a minimally
      invasive methodology that can be used to assess the genomic alterations present
      in CNS malignancies. We present a case of an 82-year-old man with a history of
      testicular lymphoma who presented with speech difficulty and a multifocal
      enhancing left inferior frontal mass. Analysis for both CSF-cytology and flow
      cytometry did not show evidence of neoplastic cells. A brain biopsy was performed
      and microscopic examination showed DLBCL. We isolated CSF-ctDNA and used droplet
      digital PCR (ddPCR) to detect the most common lymphoma-associated mutations in
      MYD88, L265P, and V217F. In conjunction, we evaluated the patient-matched CNS
      lymphoma tissue for MYD88 mutations. We detected the MYD88 p.L265P mutation in
      formalin fixed paraffin embedded (FFPE) tissue from the brain biopsy and the CSF
      ctDNA. In contrast, both the tumor tissue and the CSF ctDNA were negative for the
      MYD88 p.V217F mutation. This study shows that testing CSF ctDNA for MYD88
      mutations is a potentially minimally-invasive approach to diagnosing patients
      with suspected CNS lymphomas.

PMID- 30294591
TI  - The Formin mDia1 Regulates Acute Lymphoblastic Leukemia Engraftment, Migration,
      and Progression in vivo.
AB  - Leukemias typically arise in the bone marrow and then spread to the blood and
      into other tissues. To disseminate into tissues, leukemia cells migrate into the
      blood stream and then exit the circulation by migrating across vascular
      endothelial barriers. Formin proteins regulate cytoskeletal remodeling and cell
      migration of normal and malignant cells. The Formin mDia1 is highly expressed in
      transformed lymphocytes and regulates lymphocyte migration. However, the role of
      mDia1 in regulating leukemia progression in vivo is unknown. Here, we
      investigated how mDia1 mediates the ability of leukemia cells to migrate and
      disseminate in vivo. For these studies, we used a mouse model of Bcr-Abl pre-B
      cell acute lymphoblastic leukemia. Our data showed that mDia1-deficient leukemia
      cells have reduced chemotaxis and ability to complete transendothelial migration
      in vitro. In vivo, mDia1 deficiency reduced the ability of leukemia cells to
      engraft in recipient mice. Furthermore, leukemia dissemination to various tissues
      and leukemia progression were inhibited by mDia1 depletion. Finally, mDia1
      depletion in leukemia cells resulted in prolonged survival of recipient mice in a
      leukemia transfer model. Overall, our data show that the Formin mDia1 mediates
      leukemia cell migration, and drives leukemia engraftment and progression in vivo,
      suggesting that targeting mDia1 could provide a new method for treatment of
      leukemia.

PMID- 30294592
TI  - Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection
      Induced Endometritis in Women.
AB  - Sexually transmitted infection (STI) of the upper reproductive tract can result
      in inflammation and infertility. A biomarker of STI-induced upper tract
      inflammation would be significant as many women are asymptomatic and delayed
      treatment increases risk of sequelae. Blood mRNA from 111 women from three
      cohorts was profiled using microarray. Unsupervised analysis revealed a
      transcriptional profile that distinguished 9 cases of STI-induced endometritis
      from 18 with cervical STI or uninfected controls. Using a hybrid feature
      selection algorithm we identified 21 genes that yielded maximal classification
      accuracy within our training dataset. Predictive accuracy was evaluated using an
      independent testing dataset of 5 cases and 10 controls. Sensitivity was evaluated
      in a separate test set of 12 women with asymptomatic STI-induced endometritis in
      whom cervical burden was determined by PCR; and specificity in an additional test
      set of 15 uninfected women with pelvic pain due to unknown cause. Disease module
      preservation was assessed in 42 women with a clinical diagnosis of pelvic
      inflammatory disease (PID). We also tested the ability of the biomarker to
      discriminate STI-induced endometritis from other diseases. The biomarker was
      86.7% (13/15) accurate in correctly distinguishing cases from controls in the
      testing dataset. Sensitivity was 83.3% (5/6) in women with high cervical
      Chlamydia trachomatis burden and asymptomatic endometritis, but 0% (0/6) in women
      with low burden. Specificity in patients with non-STI-induced pelvic pain was
      86.7% (13/15). Disease modules were preserved in all 8 biomarker predicted cases.
      The 21-gene biomarker was highly discriminatory for systemic infections, lupus,
      and appendicitis, but wrongly predicted tuberculosis as STI-induced endometritis
      in 52.4%. A 21-gene biomarker can identify asymptomatic women with STI-induced
      endometritis that places them at risk for chronic disease development and
      discriminate STI-induced endometritis from non-STI pelvic pain and other
      diseases.

PMID- 30294593
TI  - OmpR-Mediated Transcriptional Regulation and Function of Two Heme Receptor
      Proteins of Yersinia enterocolitica Bio-Serotype 2/O:9.
AB  - We show that Yersinia enterocolitica strain Ye9 (bio-serotype 2/O:9) utilizes
      heme-containing molecules as an iron source. The Ye9 genome contains two
      multigenic clusters, hemPRSTUV-1 and hemPRST-2, encoding putative heme receptors
      HemR1 and HemR2, that share 62% amino acid identity. Expression of these proteins
      in an Escherichia coli mutant defective in heme biosynthesis allowed this strain
      to use hemin and hemoglobin as a source of porphyrin. The hemPRSTUV-1 and hemPRST
      2 clusters are organized as operons, expressed from the phem-1 and weaker phem-2
      promoters, respectively. Expression of both operons is negatively regulated by
      iron and the iron-responsive transcriptional repressor Fur. In addition, OmpR,
      the response regulator of two component system (TCSs) EnvZ/OmpR, represses
      transcription of both operons through interaction with binding sequences
      overlapping the -35 region of their promoters. Western blot analysis of the level
      of HemR1 in ompR, fur, and ompRfur mutants, showed an additive effect of these
      mutations, indicating that OmpR may regulate HemR expression independently of
      Fur. However, the effect of OmpR on the activity of the phem-1 promoter and on
      HemR1 production was observed in both iron-depleted and iron-replete conditions,
      i.e., when Fur represses the iron-regulated promoter. In addition, a hairpin RNA
      thermometer, composed of four uracil residues (FourU) that pair with the ribosome
      binding site in the 5'-untranslated region (5'-UTR) of hemR1 was predicted by in
      silico analysis. However, thermoregulated expression of HemR1 could not be
      demonstrated. Taken together, these data suggest that Fur and OmpR control
      iron/heme acquisition via a complex mechanism based on negative regulation of
      hemR1 and hemR2 at the transcriptional level. This interplay could fine-tune the
      level of heme receptor proteins to allow Y. enterocolitica to fulfill its
      iron/heme requirements without over-accumulation, which might be important for
      pathogenic growth within human hosts.

PMID- 30294594
TI  - Astragalus Oral Solution Ameliorates Allergic Asthma in Children by Regulating
      Relative Contents of CD4+CD25highCD127low Treg Cells.
AB  - Objective: To explore the effects of Astragalus oral solution (AOS) on allergic
      asthma in children by investigating relative contents of CD4+CD25highCD127low
      Treg cells. Methods: The contents of Astragaloside A in AOS were detected by
      using HPLC. Eighty children with allergic asthma were recruited from February
      2016 to June 2017, and randomly assigned into the control group (received
      placebo, 0.1% quinine chloride in deionized water, daily) and the AOS group
      (received 10 mL AOS daily). After 6-month treatment, therapeutic results were
      compared between the two groups. Serum levels of IL-10 and TGF-beta, Th1
      cytokines (IL-2 and IFN-gamma), and Th2 cytokines (IL-4 and IL-6) were measured
      by using ELISA kits. Relative contents of CD4+CD25highCD127low Treg cells were
      determined by using flow cytometry. Results: Astragaloside A was the main
      ingredient of AOS with 0.216 +/- 0.027 mg/mL from six-batch samples. After 6
      month therapy, the AOS group showed improved forced expiratory volume in 1 s
      (FEV1) and the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) scores
      compared with the control group (P < 0.05). Serum level of IL-10 was higher and
      the levels of TGF-beta, Th1 cytokines (IL-2 and IFN-gamma), and Th2 cytokines (IL
      4 and IL-6) were lower in the AOS group than in the control group (P < 0.05). AOS
      treatment increased the percentage of gated CD4+ T cells, CD4+CD25+ T cells,
      CD4+CD25high Treg cells, CD4+CD25+FoxP3+ Treg cells and CD4+CD25highCD127low Treg
      cells when compared with the control group (P < 0.05). Conclusions: Astragaloside
      A was the main component of AOS, and AOS ameliorated allergic asthma in children
      by regulating relative contents of CD4+CD25highCD127low Treg cells.

PMID- 30294595
TI  - Impact of Chronic Medical Conditions on Academics of Children in the Child
      Welfare System.
AB  - Objective: Children in the Child Welfare System (CWS) are at high risk for
      multiple adverse outcomes. Since involvement in CWS and having a chronic medical
      condition are both risk factors for poor academic achievement, a logical view is
      that the combination is additive, increasing the odds of poor performance.
      However, several factors may complicate such an association. This study explores
      negative and positive factors that could affect academic achievement in children
      in CWS with chronic medical conditions. Method: In a secondary data analysis of a
      nationally representative, longitudinal sample of children in CWS (N = 5,501),
      subjects were divided into three groups based on chronic medical condition: High
      Prevalence, Low Severity (HPLS; asthma, eczema, allergy, diabetes), Other (OTH;
      all other chronic conditions, including those with primary central nervous system
      involvement), and NONE (children with no chronic condition). Using weighted
      analyses, hierarchical logistic regression models addressed factors associated
      with academic achievement. Predictor variables included chronic condition group,
      sex, income level, case substantiation, home placement, and school engagement.
      Intelligence quotient was a covariate. Outcome variables were strong performances
      for reading and math, defined by standard score >=85. Results: In TOTAL group,
      80% had strong reading; more in HPLS (85%) vs. NONE (79%) and OTH (80%), adjusted
      F = 433, p < 0.001. In TOTAL group, 67% had strong math; more in NONE (68%) and
      HPLS (68%) vs. OTH (60%), adjusted F = 1,278, p < 0.001. Models predicting to
      strong reading and math achievement were significant, R 2 = 0.51, p < 0.001 and R
      2 = 0.43, p < 0.001, respectively. HPLS had increased odds of strong reading
      achievement (aOR 1.3, 95% CI 1.3-1.4); both HPLS and OTH had lower odds of strong
      math achievement (aOR 0.87 and 0.76), p < 0.001, respectively. Male sex had lower
      odds of strong reading (aOR 0.44) and math achievement (aOR 0.62); positive
      school engagement had higher odds of strong reading (aOR 1.18) and math
      achievement (aOR 2.04), all p < 0.001. Conclusion: If true, our findings
      challenge the general belief that chronic illness can only be associated with
      negative outcomes and that cumulative adversities are simply additive in terms of
      risk. Increased contact with the medical system may provide an opportunity for
      improving reading achievement for children in CWS and promoting positive school
      engagement.

PMID- 30294596
TI  - Producing 3D Biomimetic Nanomaterials for Musculoskeletal System Regeneration.
AB  - The human musculoskeletal system is comprised mainly of connective tissues such
      as cartilage, tendon, ligaments, skeletal muscle, and skeletal bone. These
      tissues support the structure of the body, hold and protect the organs, and are
      responsible of movement. Since it is subjected to continuous strain, the
      musculoskeletal system is prone to injury by excessive loading forces or aging,
      whereas currently available treatments are usually invasive and not always
      effective. Most of the musculoskeletal injuries require surgical intervention
      facing a limited post-surgery tissue regeneration, especially for widespread
      lesions. Therefore, many tissue engineering approaches have been developed
      tackling musculoskeletal tissue regeneration. Materials are designed to meet the
      chemical and mechanical requirements of the native tissue three-dimensional (3D)
      environment, thus facilitating implant integration while providing a good
      reabsorption rate. With biological systems operating at the nanoscale,
      nanoengineered materials have been developed to support and promote regeneration
      at the interprotein communication level. Such materials call for a great
      precision and architectural control in the production process fostering the
      development of new fabrication techniques. In this mini review, we would like to
      summarize the most recent advances in 3D nanoengineered biomaterials for
      musculoskeletal tissue regeneration, with especial emphasis on the different
      techniques used to produce them.

PMID- 30294598
TI  - Genome Editing Reveals Idiosyncrasy of CNGA2 Ion Channel-Directed Antibody
      Immunoreactivity Toward Oxytocin.
AB  - Presynaptic cGMP-gated ion (CNG) channels positively or negatively modulate
      neurotransmitter secretion as well as the strength of synaptic transmission.
      Zebrafish cGMP-gated ion channel, CNGA2a (a.k.a. CNGA5), was previously reported
      to be specifically enriched in synaptic terminals of zebrafish oxytocin (OXT)
      neurons. This conclusion was based on immunoreactivity of a monoclonal antibody
      (mAb) clone L55/54, which was directed against the carboxy terminal tail of the
      CNGA2a. To study the role of CNGA2a in oxytocin neurons function, we generated
      zebrafish mutants of cnga2a, cnga2b and oxt genes using clustered regularly
      interspaced short palindromic repeats (CRISPR)-mediated genome editing. We show
      that mAb L55/54 specifically recognizes CNGA2a protein when expressed in
      heterologous cell culture system. Surprisingly, anti-CNGA2a immunoreactivity was
      not eliminated following knockout of either cnga2a, cnga2b or both. However,
      knockout of oxt resulted in total loss of anti-CNGA2a mAb immunoreactivity
      despite the lack of sequence and structural similarities between OXT and CNGA2a
      proteins. Our results provide a noteworthy lesson of differences in antibody
      immunoreactivity, which could only be revealed using specific genetic tools.

PMID- 30294599
TI  - What Is Health Information Quality? Ethical Dimension and Perception by Users.
AB  - Introduction: The popularity of seeking health information online makes
      information quality (IQ) a public health issue. The present study aims at
      building a theoretical framework of health information quality (HIQ) that can be
      applied to websites and defines which IQ criteria are important for a website to
      be trustworthy and meet users' expectations. Methods: We have identified a list
      of HIQ criteria from existing tools and assessment criteria and elaborated them
      into a questionnaire that was promoted via social media and mainly the
      University. Responses (329) were used to rank the different criteria for their
      importance in trusting a website and to identify patterns of criteria using
      hierarchical cluster analysis. Results: HIQ criteria were organized in five
      dimensions based on previous theoretical frameworks as well as on how they
      cluster together in the questionnaire response. We could identify a top-ranking
      dimension (scientific completeness) that describes what the user is expecting to
      know from the websites (in particular: description of symptoms, treatments, side
      effects). Cluster analysis also identified a number of criteria borrowed from
      existing tools for assessing HIQ that could be subsumed to a broad "ethical"
      dimension (such as conflict of interests, privacy, advertising policies) that
      were, in general, ranked of low importance by the participants. Subgroup analysis
      revealed significant differences in the importance assigned to the various
      criteria based on gender, language and whether or not of biomedical educational
      background. Conclusions: We identified criteria of HIQ and organized them in
      dimensions. We observed that ethical criteria, while regarded highly in the
      academic and medical environment, are not considered highly by the public.

PMID- 30294600
TI  - Effects of Caffeine Ingestion on Anaerobic Capacity in a Single Supramaximal
      Cycling Test.
AB  - The aim of this study was to verify the effects of caffeine on anaerobic capacity
      estimated by the sum of the estimated glycolytic [E[La]] and phosphagen [EPCr]
      metabolism based on blood lactate and excess post-oxygen consumption responses
      (AC[La-]+EPOCfast). Fourteen male cyclists were submitted to a graded exercise
      test to determine the maximal oxygen uptake ( V degrees O2max ) and intensity
      associated with  V degrees O2max (i V degrees O2max ). Subsequently, the
      participants performed two supramaximal efforts at 115% of i V degrees O2max to
      determine the AC[La-]+EPOCfast, after previous supplementation with caffeine (6
      mg.kg-1) or a placebo (dextrose), in a cross over, randomized, double blind, and
      placebo-controlled design. The time to exhaustion was higher in the caffeine
      (186.6 +/- 29.8 s) than in the placebo condition (173.3 +/- 25.3 s) (p = 0.006)
      and a significant correlation was found between them (r = 0.86; P = 0.00008).
      Significant differences were not found between AC[La-]+EPOCfast values from the
      placebo (4.06 +/- 0.83 L and 55.2 +/- 5.7 mL.kg-1) and caffeine condition (4.00
      +/- 0.76 L and 54.6 +/- 5.4 mL.kg-1); however, a significant correlation was
      observed only for AC[La-]+EPOCfast expressed in absolute values (r = 0.74; p <
      0.002). The E[La] and EPCr also presented no significant differences and they
      were significantly correlated (r = 0.82 and r = 0.55, respectively; p < 0.05). We
      conclude based on the overall comparison of mean values between two treatments
      that acute caffeine ingestion improves the time to exhaustion but does not affect
      anaerobic capacity estimation.

PMID- 30294597
TI  - Genetic Models of Leukemia in Zebrafish.
AB  - The zebrafish animal model is gaining increasing popularity as a tool for
      studying human disease. Over the past 15 years, many models of leukemia and other
      hematological malignancies have been developed in the zebrafish. These confer
      some significant advantages over similar models in other animals and systems,
      representing a powerful resource for investigation of the molecular basis of
      human leukemia. This review discusses the various zebrafish models of lymphoid
      and myeloid leukemia available, the major discoveries that have been made
      possible by them, and opportunities for future exploration.

PMID- 30294601
TI  - Descending Perineum Associated With Pelvic Organ Prolapse Treated by Sacral
      Colpoperineopexy and Retrorectal Mesh Fixation: Preliminary Results.
AB  - Introduction and hypothesis: Descending Perineum Syndrome (DPS) is a
      coloproctologic disease and the best treatment for it is yet to be defined. DPS
      is frequently associated with pelvic organ prolapse (POP) and it is reasonable to
      postulate, that treatment of POP will also have an impact on DPS. We aimed to
      evaluate the subjective satisfaction and improvement of DPS for patients who have
      undergone a sacral colpoperineopexy associated with retrorectal mesh for
      concomitant POP. Methods: This retrospective cohort study, conducted between
      February 2010 and May 2016 included all women who had undergone surgery to treat
      POP and DPS. Improvement of POP was assessed clinically and subjective
      satisfaction was assessed with a survey. Results: Among the 37 operated patients,
      31 responded to the questionnaire and 77.4% were satisfied with this surgical
      procedure. 94.6% were objectively cured for POP. There was a 60% improvement rate
      for constipation, 63.5 and 68% were cured or improved for ODS and the need for
      digital maneuvers respectively. Conclusion: Sacral colpoperineopexy associated
      with retrorectal dorsal mesh appears to objectively and subjectively improve POP
      associated with DPS.

PMID- 30294602
TI  - Endovascular Neurosurgery in the Netherlands: Historical Developments and
      Achievements.
AB  - The historical developments of endovascular neurosurgery in the Netherlands are
      described.

PMID- 30294603
TI  - Microbiome and Blood Analyte Differences Point to Community and Metabolic
      Signatures in Lean and Obese Horses.
AB  - Due to modern management practices and the availability of energy dense feeds,
      obesity is a serious and increasingly common health problem for horses. Equine
      obesity is linked to insulin resistance and exacerbation of inflammatory issues
      such as osteoarthritis and laminitis. While the gut microbiome is thought to play
      a part in metabolic status in horses, bacterial communities associated with
      obesity have yet to be described. Here we report differences in metabolic factors
      in the blood of obese, normal and lean horses correlated with differences in gut
      microbiome composition. We report that obese horses had higher levels of leptin,
      triglycerides, glucose, and cortisol in their blood, and more diverse gut
      microbiome communities with higher relative abundance of Firmicutes, and lower
      numbers of Bacteroidetes and Actinobacteria. Network analyses of correlations
      between body condition, blood analytes, and microbial composition at the genus
      level revealed a more nuanced picture of microbe-host interactions, pointing to
      specific bacterial species and assemblages that may be signatures of obesity and
      leanness in the horse gut. In particular, bacteria groups positively associated
      with two blood analytes and obesity included Butyrivibrio spp., Prevotellaceae,
      Blautia spp., two members of Erysipelotrichaceae, and a Lachnospiraceae taxa.
      These results are an important first step in unraveling the metabolic differences
      between obese and lean horse gut communities, and designing targeted strategies
      for microbial intervention.

PMID- 30294604
TI  - Defensive medicine: It is time to finally slow down an epidemic.
AB  - Defensive medicine is widespread and practiced the world over, with serious
      consequences for patients, doctors, and healthcare costs. Even students and
      residents are exposed to defensive medicine practices and taught to take
      malpractice liability into consideration when making clinical decisions.
      Defensive medicine is generally thought to stem from physicians' perception that
      they can easily be sued by patients or their relatives who seek compensation for
      presumed medical errors. However, in our view the growth of defensive medicine
      should be seen in the context of larger changes in the conception of medicine
      that have taken place in the last few decades, undermining the patient-physician
      trust, which has traditionally been the main source of professional satisfaction
      for physicians. These changes include the following: time directly spent with
      patients has been overtaken by time devoted to electronic health records and desk
      work; family doctors have played a progressively less central role; clinical
      reasoning is being replaced by guidelines and algorithms; the public at large and
      a number of young physicians tend to believe that medicine is a perfect science
      rather than an imperfect art, as it continues to be; and modern societies do not
      tolerate the inevitable morbidity and mortality. To finally reduce the increasing
      defensive behavior of doctors around the world, the decriminalization of medical
      errors and the assurance that they can be dealt with in civil courts or by
      medical organizations in all countries could help but it would not suffice.
      Physicians and surgeons should be allowed to spend the time they need with their
      patients and should give clinical reasoning the importance it deserves. The
      institutions should support the doctors who have experienced adverse patient
      events, and the media should stop reporting with excessive evidence presumed
      medical errors and subject physicians to "public trials" before they are
      eventually judged in court.

PMID- 30294605
TI  - Web-based learning in inflammatory bowel diseases: General truths and current
      specifics.
AB  - In a field rapidly evolving over the past few years, the management of
      inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, is
      becoming increasingly complex, demanding and challenging. In the recent years,
      IBD quality measures aiming to improve patients' care have been developed,
      multiple new medical therapies have been approved, new treatment goals have been
      set with the "treat-to-target" concept and drug monitoring has been implemented
      into IBD clinical management. Moreover, patients are increasingly using Internet
      resources to obtain information about their health conditions. The healthcare
      professional with an interest in treating IBD patients should deal with all these
      challenges in everyday practice by establishing, enhancing and maintaining a
      strong core of knowledge and skills related to IBD. This is an ongoing process
      and traditionally these needs are covered with additional reading of textbook or
      journal articles, attendance at meetings or conferences, or at local rounds. Web
      based learning resources expand the options for knowledge acquisition and save
      time and costs as well. In the new era of communications technology, web-based
      resources can cover the educational needs of both patients and healthcare
      professionals and can contribute to improvement of disease management and patient
      care. Healthcare professionals can individually visit and navigate regularly
      relevant websites and tailor choices for educational activities according to
      their existing needs. They can also provide their patients with a few certified
      suitable internet resources. In this review, we explored the Internet using
      PubMed and Startpage (Google), for web-based IBD-related educational resources
      aiming to provide a guide for those interested in obtaining certified knowledge
      in this subject.

PMID- 30294606
TI  - Dual HER2 inhibition strategies in the management of treatment-refractory
      metastatic colorectal cancer: History and status.
AB  - Human epidermal growth factor receptor 2 (HER2) signaling pathway activation has
      been identified as a contributor to de novo or acquired resistance to epidermal
      growth factor receptor (EGFR) inhibitors in a small subset of patients with
      metastatic colorectal cancer (mCRC). Dual anti-HER2-targeted treatment exhibits
      strong antitumor activity in preclinical models of HER2-positive mCRC, supporting
      its testing in clinical trials. The HERACLES trial at four Italian academic
      cancer centers has confirmed the effectiveness of dual blockage of HER2 with
      trastuzumab plus lapatinib in patients with heavily pretreated HER2-positive
      mCRC, refractory to the anti-EGFR antibodies cetuximab or panitumumab. Here, we
      reviewed the preclinical studies exploring the role of HER2 signaling in the
      development of anti-EGFR therapy resistance and discussed the status of clinical
      trials assessing the activity of HER2 inhibitors in this setting.

PMID- 30294607
TI  - Isolation and characterization of a new candidate human inactivated rotavirus
      vaccine strain from hospitalized children in Yunnan, China: 2010-2013.
AB  - AIM: To determine the distribution of rotavirus VP7 gene in hospitalized children
      in Yunnan, China. METHODS: A total of 366 stool specimens were collected from
      hospitalized children in hospitals in Yunnan Province from September 2010 to
      December 2013. The genomic RNA electropherotypes and the G genotypes of the
      rotaviruses were determined. A phylogenetic analysis of the VP7 gene was
      performed. Rotavirus isolation was performed, and characterized by plaque,
      minimum essential medium, and all genes sequence analysis. Quantification of
      antibodies for inactivated vaccine prepared with ZTR-68 was examined by enzyme
      linked immunosorbent assay and microneutralization assay. RESULTS: Group A human
      rotavirus was detected in 177 of 366 (48.4%) stool samples using a colloidal gold
      device assay. The temporal distribution of rotavirus cases showed significant
      correlation with the mean air temperature. Rotaviruses were isolated from 13% of
      the rotavirus-positive samples. The predominant genotype was G1 (43.5%), followed
      by G3 (21.7%), G9 (17.4%), G2 (4.3%), G4 (8.7%), and mixed (4.3%) among a total
      of 23 rotavirus isolates. A rotavirus strain was isolated from a rotavirus
      positive stool sample of a 4-month-old child in The First People's Hospital of
      Zhaotong (2010) for use as a candidate human inactivated rotavirus vaccine strain
      and for further research, and was designated ZTR-68. The genotype of 11 gene
      segments of strain ZTR-68 (RVA/Human-wt/CHN/ZTR-68/2010/G1P[8]) was
      characterized. The genotype constellation of strain ZTR-68 was identified as G1
      P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. The VP7 and VP4 genotypes of strain ZTR-68 were
      similar to Wa-like strains.CONCLUSIONSA high prevalence of the G1, G2, and G3
      genotypes was detected from 2010 to 2012. However, a dominant prevalence of the
      G9 genotype was identified as the cause of gastroenteritis in children in Yunnan,
      China, in 2013. A candidate human inactivated rotavirus vaccine strain,
      designated ZTR-68 was isolated, characterized, and showed immunogenicity. Our
      data will be useful for the future formulation and development of a vaccine in
      China.

PMID- 30294608
TI  - Diagnostic value of elevated serum carbohydrate antigen 199 level in acute
      cholangitis secondary to choledocholithiasis.
AB  - AIM: To investigate the diagnostic value of abnormal serum carbohydrate antigen
      199 (CA199) level in acute cholangitis secondary to choledocholithiasis. METHODS:
      In this retrospective cohort study, the clinical data of 727 patients with
      choledocholithiasis admitted to the Third Affiliated Hospital of Zunyi Medical
      College from June 2011 to June 2017 were collected. Among these patients, 258
      patients had secondary acute cholangitis and served as observation group, and the
      remaining 569 choledocholithiasis patients served as the control group. Serum
      liver function indexes and tumor markers were detected in both groups, and the
      receiver operating characteristic (ROC) curves were constructed for markers
      showing statistical significances. The cutoff value, sensitivity, and specificity
      of each marker were calculated according to the ROC curves. RESULTS: The results
      of liver function tests showed no significant differences between the two groups
      (P > 0.05). Tumor markers including serum CA125, CA153, carcinoembryonic antigen,
      and alpha fetoprotein levels were also not significantly different (P > 0.05);
      however, the serum CA199 level was significantly higher in the observation group
      than in the control group (P < 0.05). The ROC curve analysis showed that the area
      under the curve was 0.885 (95%CI: 0.841-0.929) for CA199, and the cutoff value of
      52.5 kU/L had the highest diagnostic accuracy, with a sensitivity of 86.8% and a
      specificity of 81.6%. CONCLUSION: Abnormally elevated serum CA199 level has an
      important value in the diagnosis of acute cholangitis secondary to
      choledocholithiasis. It may be a specific inflammatory marker for acute
      cholangitis.

PMID- 30294610
TI  - Neurofibroma discharged from the anus with stool: A case report and review of
      literature.
AB  - Isolated neurofibromas that affect the gastrointestinal tract are rare and almost
      always manifest as neurofibromatosis type 1 or multiple endocrine neoplasia type
      2b. In this paper, we present a case of a 24-year-old female with abdominal pain
      who discharged a neurofibroma in her stool without any blood on it. A colonoscopy
      showed multiple small polyps in the sigmoid colon and a nodule in the ileocecus.
      The pathology results and the immunohistochemical stains of the removed neoplasm
      from the ileocecus confirmed the diagnosis was a bowel neurofibroma. We report a
      rare case of ileocecal neurofibroma due to the patient's affected
      gastrointestinal tract, without any associated systemic syndrome other than a
      neurofibroma discharged in the stool.

PMID- 30294609
TI  - Balo's concentric sclerosis in a patient with spontaneous remission based on
      magnetic resonance imaging: A case report and review of literature.
AB  - Balo's concentric sclerosis (BCS) is a rare monophasic demyelinating disease
      known as multiple sclerosis subtype and seen as a round lesion with variable
      hyper and hypo-detoxification layers. Characteristic appearance can be seen as
      "bulb eye" or "onion bulb". The initial terminology for this neurological
      disorder was leukoencephalitis periaxialis concentrica; this is defined as a
      disease in which the white matter of the brain is destroyed in concentric layers
      in such a way as to leave the axial cylinders intact. This report presents a case
      of BCS with spontaneous healing of the patient and a mass lesion with concentric
      rings adjacent to the left lateral ventricle and the posterior portion of the
      corpus callosum with peripheral vasogenic edema. The neurological lesion of the
      patient was similar to the magnetic resonance imaging and clinical findings of
      the BCS.

PMID- 30294611
TI  - Balloon dilator controls massive bleeding during endoscopic ultrasound-guided
      drainage for pancreatic pseudocyst: A case report and review of literature.
AB  - Pancreatic pseudocyst (PPC), a common sequela of acute or chronic pancreatitis,
      was defined by the revised Atlanta classification as "a collection." Endoscopic
      ultrasound (EUS)-guided drainage is often considered a standard first-line
      therapy for patients with symptomatic PPC. This effective approach exhibits 90%
      100% technical success and 85%-98% clinical success. Bleeding is a deadly adverse
      event associated with EUS-guided drainage procedures, and the bleeding rate
      ranges from 3% to 14%. Hemostasis involves conservative treatment, endoscopy,
      interventional radiology-guided embolization and surgery. However, few studies
      have reported on EUS-guided drainage with massive, multiple hemorrhages related
      to severe pancreatogenic portal hypertension (PPH). Thus, the aim of this case
      report was to present a case using a balloon dilator to achieve successful
      hemostasis for PPH-related massive bleeding in EUS-guided drainage of PPC. To our
      knowledge, this method has not been previously reported.

PMID- 30294612
TI  - Twin pregnancy with triple parathyroid adenoma: A case report and review of
      literature.
AB  - Primary hyperparathyroidism (PHPT) is rare during pregnancy. A case of twin
      pregnancy with three simultaneous parathyroid adenomas at the same time has not
      been reported. Multiple parathyroid lesions are difficult to diagnose, as
      pregnant women who insist upon continuing a pregnancy are not able to undergo
      99mTc-sestamibi scintigraphy, so cases of PHPT are easily unobserved and often
      can have serious consequences for the patient and the fetus. Therefore, we
      reported a case of a 28-year-old woman mid-pregnancy with twins, who had
      hypercalcemia and was eventually diagnosed with twin pregnancy with PHPT due to a
      triple parathyroid adenoma, had good pregnancy outcomes after undergoing surgery
      in mid-pregnancy. Twin pregnancy with PHPT due to a triple parathyroid adenoma,
      as presented in this case, is very rare and surgery in mid-pregnancy is
      demonstrated here as safe. Intraoperative parathormone monitoring was and remains
      key to a successful operation.

PMID- 30294613
TI  - Unusual cause of lesions in the descending duodenum and liver: A case report and
      review of literature.
AB  - The descending duodenum is rarely involved in Schistosoma japonicum (S.
      japonicum) infection. Here, we report a case of acute Schistosoma infection,
      which presented with abdominal pain, abdominal distension and irregular fever.
      Tumor-like lesions were observed in the descending duodenum. Simultaneously,
      heterogeneity in hepatic perfusion was demonstrated by dynamic computed
      tomography scanning. Biopsy of the descending duodenum showed the deposition of
      Schistosoma eggs. Following administration of the antihelminthic drug
      praziquantel, the patient showed rapid clinical improvement. In conclusion, we
      report a patient with acute S. japonicum infection presenting as tumor-like
      lesions in the descending duodenum and heterogeneity of blood perfusion in liver
      parenchyma.

PMID- 30294614
TI  - Isolated myeloid sarcoma in the pancreas and orbit: A case report and review of
      literature.
AB  - Myeloid sarcoma (MS) is a type of extramedullary solid haematological tumour.
      Myeloid sarcoma is classified into two types based on whether onset of the
      disease is complicated by haematologic diseases: extramedullary infiltration of
      leukaemia (leukaemic MS) and isolated myeloid sarcoma. The incidence of isolated
      myeloid sarcoma is low. In particular, isolated myeloid sarcoma involving the
      pancreas is extremely rare and prone to misdiagnosis. This case report describes
      the long and eventful diagnostic process of a case of myeloid sarcoma involving
      the pancreas and orbit. Due to a lack of typical clinical manifestations and
      imaging characteristics, the patient underwent several rounds of treatment
      without a confirmed diagnosis. Eventually, the final diagnosis was pathologically
      confirmed using several types of biopsies and immunohistochemical detection. To
      date, this type of disease has not been reported in the literature. This case
      report describes the detailed diagnostic process and discusses the strategies
      used for diagnosis, which will facilitate the diagnosis of such diseases in the
      future.

PMID- 30294615
TI  - Genotyping of Pulmonary Mycobacterium tuberculosis Isolates from Sudan Using
      Spoligotyping.
AB  - Tuberculosis (TB) remains a major public health problem worldwide due to its high
      risk of person-to-person transmission, morbidity and mortality [1]. Sudan has a
      high burden of tuberculosis. Spoligotyping (spacer oligonucleotide typing) a
      rapid method for genotyping of Mycobacterium tuberculosis using the principle of
      reverse hybridization. The ecology of the prevalent mycobacteria strain can vary
      depending on country and region. The aim of this study was to determine the
      genotyping of Mycobacterium tuberculosis isolated from Sudan using spoligotyping
      SPOLDB4. A total of 75 Mycobacterium tuberculosis sputum samples were collected
      from pulmonary Tuberculosis patients attending references Laboratories and
      diagnostic centers in Khartoum and Eastern Sudan in (2011-2013). The mycobacteria
      were genotyped using Spoligotyping technique and data obtained were analyzed and
      compared to the SPOLDB4 database. Among the 75 isolate analyzed, 57(76%) were
      identified by SPOLDB4 and 18 (24%) could not be matched to any lineages. The most
      prevalent genotype cluster was MANU2 38 (50.7%) followed by CASI Delhi 8 (10.7%).
      In the study SIT54 was the most common pattern 37 (49.3%) followed by SIT25
      6(8%).

PMID- 30294617
TI  - Infectious MERS-CoV Isolated From a Mildly Ill Patient, Saudi Arabia.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with a wide
      range of clinical presentations, from asymptomatic or mildly ill to severe
      respiratory illness including death. We describe isolation of infectious MERS-CoV
      from the upper respiratory tract of a mildly ill 27-year-old female in Saudi
      Arabia 15 days after illness onset.

PMID- 30294618
TI  - Validation of an Immunoassay for Anti-thymidine Phosphorylase Antibodies in
      Patients with MNGIE Treated with Enzyme Replacement Therapy.
AB  - Erythrocyte encapsulated thymidine phosphorylase is recombinant Escherichia coli
      thymidine phosphorylase encapsulated within human autologous erythrocytes and is
      under development as an enzyme replacement therapy for the ultra-rare inherited
      metabolic disorder mitochondrial neurogastrointestinal encephalomyopathy. This
      study describes the method validation of a two-step bridging
      electrochemiluminescence immunoassay for the detection of anti-thymidine
      phosphorylase antibodies in human serum according to current industry practice
      and regulatory guidelines. The analytical method was assessed for screening cut
      point, specificity, selectivity, precision, prozone effect, drug tolerance, and
      stability. Key findings were a correction factor of 129 relative light units for
      the cut-point determination; a specificity cut point of 93% inhibition; confirmed
      intra-assay and inter-assay precision; assay sensitivity of 356 ng/mL; no matrix
      or prozone effects up to 25,900 ng/mL; a drug tolerance of 156 ng/mL; and
      stability at room temperature for 24 hr and up to five freeze-thaws.
      Immunogenicity evaluations of serum from three patients who received erythrocyte
      encapsulated thymidine phosphorylase under a compassionate treatment program
      showed specific anti-thymidine phosphorylase antibodies in one patient. To
      conclude, a sensitive, specific, and selective immunoassay has been validated for
      the measurement of anti-thymidine phosphorylase antibodies; this will be utilized
      in a phase II pivotal clinical trial of erythrocyte encapsulated thymidine
      phosphorylase.

PMID- 30294616
TI  - Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion
      Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation.
AB  - Background: An outbreak of Middle East respiratory syndrome coronavirus (MERS
      CoV) in Jordan in 2015 involved a variant virus that acquired distinctive
      deletions in the accessory open reading frames. We conducted a molecular and
      seroepidemiologic investigation to describe the deletion variant's transmission
      patterns and epidemiology. Methods: We reviewed epidemiologic and medical chart
      data and analyzed viral genome sequences from respiratory specimens of MERS-CoV
      cases. In early 2016, sera and standardized interviews were obtained from MERS
      CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike
      protein enzyme immunoassays and microneutralization. Results: Among 16 cases, 11
      (69%) had health care exposure and 5 (31%) were relatives of a known case; 13
      (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13
      cases revealed 3 transmissible deletions associated with clinical illness during
      the outbreak. Deletion variant sequences were epidemiologically clustered and
      linked to a common transmission chain. Interviews and sera were collected from 2
      surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%)
      case, 2 (9%) household contacts, and 3 (1%) health care contacts tested
      seropositive. Conclusions: The MERS-CoV deletion variants retained human-to-human
      transmissibility and caused clinical illness in infected persons despite
      accumulated mutations. Serology suggested limited transmission beyond that
      detected during the initial outbreak investigation.

PMID- 30294619
TI  - Generation of Human Mesenchymal Stem Cell 3D Spheroids Using Low-binding Plates.
AB  - The 3D culture of human mesenchymal stem cells (hMSCs) represents a more
      physiological environment than classical 2D culture and has been used to enhance
      the MSC secretome or extend cell survival after transplantation. Here we describe
      a simple and affordable method to generate 3D spheroids of hMSCs by seeding them
      at high density in a low-binding 96-well plate. Spheroids of hMSCs cultured in
      low-binding 96-well plates can be used to study the basic biology of the cells
      and to generate conditioned media or spheroids to be used in transplantation
      therapeutic approaches. These MSCs or their secretome can be used as a
      regenerative therapy and for tissue repair across multiple disease areas,
      including neurodegeneration. In comparison to other methods (hanging drop, use of
      gels or biomaterials, magnetic levitation, etc.), the method described here is
      simple and affordable with no need to use specialized equipment, expensive
      materials or complex reagents.

PMID- 30294620
TI  - Hilly or mountainous surface: a new CT feature to predict the behavior of pure
      ground glass nodules?
AB  - Persistent pure ground-glass nodules (pGGNs) typically show an indolent course
      with very slow growth rates. These slow-growing lesions exhibit different growth
      patterns regardless of their initial computed tomography (CT) features.
      Therefore, predicting the aggressive behavior of pGGNs on initial CT remains a
      diagnostic challenge. The literature reports that computerized analysis and
      various quantitative features have been tested to improve the risk stratification
      for pGGNs. The present article describes the long-term follow-up of two pGGNs
      with different behavior and introduces, for the first time, a new computerized
      method of analysis that could be helpful for predicting the future behavior of
      pGGNs.

PMID- 30294621
TI  - Data on emerging sulfur dioxide in the emission of natural gas heater in winter.
AB  - Natural gas is a kind of fuel that is used in various heating systems for
      combustion processes. Combustion of natural gas produce such air pollutants as
      CO2, NOx, SOx, PM, CO, and HC. During cold days, total gas consumption in Iran
      goes up. Thus, in these days it is likely to make some changes in gas properties
      that can affect the emissions from gas heaters. Portable flue gas analyzer
      (LANCOM III) was used for, SO2, NOX, and CXHY measurement from December 2012 to
      April 2013. Data show that emissions of pollutants from the gas heater were
      different during the cold seasons. On colder days, total gas consumption in the
      country increased, SO2 emerged in heater stack, and the concentration of
      hydrocarbons (CXHY) significantly increased as well. This emergence could be
      attributed to the changes in gas properties in the colder days. In these days,
      the transient flow and high changes of speed and pressure in the gas pipes could
      lead to release of some deposited sulfur in gas flow. Therefore, sulfur dioxide
      will be generated in the combustion process.

PMID- 30294622
TI  - Two thermal performance test (TPT) datasets of a single U-tube borehole heat
      exchanger with inlet setpoint temperatures of 30  degrees C and 40  degrees C.
AB  - The presented thermal performance test (TPT) datasets were related to the
      research article "New perspectives in thermal performance test: Cost-effective
      apparatus and extended data analysis" (Choi et al., 2018), where a new TPT
      apparatus was developed by adding a solid-state-relay and a proportional-integral
      derivative (PID) controller to a thermal response test apparatus. Using the
      developed apparatus connected to a 50-m-long vertical ground heat exchanger, two
      TPTs were conducted for 144 h with inlet setpoint temperatures of 30  degrees C
      and 40  degrees C. The raw data were measured at 5 s intervals and consisted of
      the inlet, and outlet fluid temperatures, and the flow rate. The attached MATLAB
      script allows users to easily filter the data at user-specified time intervals.
      Moreover, the execution of code provides two additional quantities: heat
      injection rate and unit heat exchange rate. The datasets are shared for the
      following purposes: (1) performance comparison of various ground heat exchangers
      using the unit heat exchange rate (2) comparison of the control performance of a
      newly developed TPT apparatus, (3) validation of an analytical or numerical
      thermal response model, and (4) validation of a parameter estimation algorithm.

PMID- 30294623
TI  - The spectrogram data of quinazoline derivatives containing a dithioacetal moiety.
AB  - The nuclear magnetic resonance, and high-resolution mass spectrometry of
      quinazoline derivatives containing a dithioacetal moiety, which was hosted in the
      research article entitled "Syntheses, antiviral activities and induced resistance
      mechanisms of novel quinazoline derivatives containing a dithioacetal moiety".
      The data include 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic
      resonance (13C NMR), and high-resolution mass spectrometry. In this article, a
      more comprehensive data interpretation and analysis is explained.

PMID- 30294624
TI  - Data for the prevalence of nurses' burnout in Iran (a meta-analysis dataset).
AB  - The present dataset was carried out using meta-analysis method towards
      investigation of the prevalence of nurses' burnout in Iran. To this end, the
      keywords were searched in the Iranian databases such as Medlib, SID, Iranmedex,
      Magiran or even some international databases such as Cochrane, Science-Direct,
      Scopus, PubMed, and Google Scholar. The data were analysed using the STATA
      Software Version 12. In ten articles with a sample size of 1758 subjects, an
      average age of 30.73 (54%) and the confidence interval of 43-64, the prevalence
      of burnout was reported. The obtained data indicated that Fars and Zanjan
      Provinces had the highest and lowest rates of burnout (72% and 26%,
      respectively). According to the acquired data, the total prevalence of burnout
      among men and women measured 46% and 65%, respectively. Given the high prevalence
      of burnout among the Iranian nurses in this dataset and the importance of nursing
      in public health which requires highly motivated and committed nurses with high
      job satisfaction, it is recommended that the intensity of burnout be reduced
      through supervising the nurses' professional performance, supporting, paying
      attention to their problems, following up and providing the necessary strategies
      to improve their environmental, economic, and personal conditions.

PMID- 30294625
TI  - Data on links between structural and functional prokaryotic diversity in long
      term sewage sludge amended soil.
AB  - The application of sewage sludge to agricultural soil induces co-exposure of
      prokaryotic populations to antibiotics and heavy metals, thus exerting a
      selection pressure that may lead to the development of antibiotic resistance.
      Here, soil samples from a long-term factorial field experiment in which sewage
      sludge was applied to agricultural soil, at different rates (40 and 80 t ha-1)
      and frequencies (every 1, 2 and 4 years) of application, were studied to assess:
      (i) the effect of sewage sludge application on prokaryotic community composition,
      (ii) the links between prokaryotic community composition and antibiotic
      resistance profiles, and (iii) the links between antibiotic resistance and
      metal(oid) concentrations in amended soil. We found no significant impact of
      sewage sludge on prokaryotic community composition. Some antibiotic resistance
      genes (ARGs) correlated positively with particular prokaryotic taxa, being
      Gemmatimonadetes the taxon with the greatest number of positive correlations at
      phylum level. No positive correlation was found between prokaryotic taxa and
      genes encoding resistance to sulfonamides and FCA. All metal(oid)s showed
      positive correlations with, at least, one ARG. Metal(oid) concentrations in soil
      also showed positive correlations with mobile genetic element genes, particularly
      with the gene tnpA-07. These data provide useful information on the links between
      soil prokaryotic composition and resistome profiles, and between antibiotic
      resistance and metal(oid) concentrations, in agricultural soils amended with
      sewage sludge.

PMID- 30294626
TI  - Dataset on the response of Hut78 cells to novel rexinoids.
AB  - This article presents the experimental data supporting analysis of differential
      gene expression of human cutaneous T cell lymphoma (CTCL) cell culture cells
      (Hut78) treated with bexarotene or a variety of rexinoids, in conjunction with "A
      Novel Gene Expression Analytics-based Approach to Structure Aided Design of
      Rexinoids for Development as Next-Generation Cancer Therapeutics" (Hanish et al.
      2018). Data presented here include microarray gene expression analysis of a
      subset of genes. A novel method for analyzing gene expression in the context of a
      model of ligand mechanism, called the Divergence Score, is described. Analysis to
      identify the presence of potential retinoid response elements in putative
      promoter regions of the study genes is also presented.

PMID- 30294627
TI  - Data on aluminum concentration in drinking water distribution network of rural
      water supply in Sistan and Baluchistan province, Iran.
AB  - The aim of this study is to determine the Aluminum concentration in groundwater
      resources of Sistan and Baluchestan province, Iran. See the data in this article.
      For the purpose of this study, a total of 871 water samples were collected and
      values of quality parameters including pH, turbidity, total dissolved solids
      (TDS) and Aluminum concentration were measured (with two-time repetitions)
      according to Standard Methods for the Examination of Water and Wastewater, during
      the year 2016. The mean, maximum, minimum of Aluminum concentrations in all
      groundwater resources of Sistan and Baluchistan province, were: 0.015, 0.059,
      0.0004 mg/l, respectively and also, the standard deviation was 0.012. Moreover,
      employing GIS software, the geo-statistical distribution of Aluminum
      concentration in groundwater aquifer in Sistan and Baluchestan was mapped.

PMID- 30294628
TI  - Dataset on the current state of air pollution in Bussau-Guinea Bussau: A
      diagnostic approach.
AB  - Recent UN report shows that over 100,000 people die from air pollution. The
      general anthropoenic pollution from Sahara desert, fossil-fuel engines and bush
      burning needs to be reduced to avoid natural accidents, regional climate change
      etc. A fifteen years dataset was obtained from the Multi-angle Imaging Spectro
      Radiometer (MISR). The dataset generated from the primary dataset would assist to
      understand the state of air pollution over Bussau. It also serves as a reference
      to guide the choice of ground measuring equipments in the area. The aerosol
      constant and tunning constant over Bussau is 0.6694 and 0.1354 respectively. The
      maximum percentage aerosol loading is given as 14.8%.

PMID- 30294629
TI  - Spectroscopy (Raman, XPS, and GDMS) and XRD analysis for studying the interaction
      between nuclear grade graphite and molten 2LiF-BeF2 (FLiBe) at 700  degrees C.
AB  - FLiBe-exposed IG-110 graphite and a control IG-110 sample were analyzed by Raman,
      XPS, GDMS, and XRD, and the complete raw data sets are provided in the
      Supplementary Information. These data sets enable full reproducibility and
      transparency of the data analysis we reported in the accompanying research paper
      titled "Fluorination of Nuclear Graphite IG-110 in Molten FLiBe salt at 700 
      degrees C", published in the Journal of Fluorine Chemistry, and facilitates
      quantitative comparison with future similar studies by other research groups. In
      this data article, we provide plots of the peak fitting for all Raman spectra
      from each sampling point on the graphite surface. We also provide the measured
      impurity concentrations of the IG-110 samples, as measured by GDMS; this data was
      not reported nor discussed in the accompanying research paper. The method and
      software used for peak fitting for the spectra from Raman, XPS, and XRD are
      listed separately.

PMID- 30294630
TI  - Dataset on non-carcinogenic risk via nitrate and nitrite in the groundwater of
      Divandarreh County, Kurdistan province, Iran: A potential concern for drinking.
AB  - The presence of elevated nitrate (NO3-) and nitrite (NO2-) concentration in
      drinking water higher than the standard limits could endanger the health of
      consumers. For this data article, concentration of NO3- and NO2- was measured in
      118 samples collected from 59 active rural wells in Divandarreh County and the
      non-carcinogenic risk in the adults and children was estimated by Monte Carlo
      simulation (MCS). The obtained data showed that the average concentration of NO3-
      and NO2- was ranges from 31.37 +/- 18.87 mg/L and 1.45 +/- 0.90 mg/L
      respectively. Based on acquired data, NO3- concentrations were 37 times higher
      than NO2- with significant p value of < 0.05. The average concentration of NO3-
      and NO2- was lower than the national standard with p value < 0.05. However, the
      concentration of NO3- and NO2- in 23.7% and 13.5% of wells was higher than the
      national standard of Iran. Total target hazard quotient (TTHQ) in the adults and
      children was 1.78 and 1.54, respectively. Although, the average concentration of
      NO3- and NO2- in drinking water was lower than the national standard limits, but
      the non-carcinogenic risk assessment showed that the children and adults are at a
      significant risk via nitrate and nitrite in the rural Divandarreh County (TTHQ >
      1).

PMID- 30294631
TI  - Biosafety of citrate coated zerovalent iron nanoparticles for Magnetic Resonance
      Angiography.
AB  - Though nanoparticles are being used for several biomedical applications, the
      safety of the same is still a concern. It is very routine procedure to check the
      preliminary safety aspects of the particles intended for in vivo applications.
      The major tests include how the material reacts to a normal cell, how it behaves
      with the blood cells and also whether any lysis take place in the presence of
      these materials. Here we present these test data of two novel nanomaterials
      designed for its use as contrast agent for magnetic resonance imaging and a
      multimodal contrast agent for targeted liver imaging. On proving the biosafety,
      the materials were tested for Magnetic Resonance Angiography using normal rats as
      model. The data of the same were clear identification of the prominent vascular
      structures and is included as the colour coded MRI image. Lateral and oblique
      view data are also presented for visualizing other major blood vessels.

PMID- 30294632
TI  - Data of numerical simulation and experimental research on the design of a cyclone
      separator with a high flux density.
AB  - This article contains data related to the research article entitled "Cyclone
      separator for gas-liquid mixture with high flux density" (Mikheev et al., 2018
      [1]doi: 10.1016/j.powtec.2018.08.040). This work was aimed at the development of
      an effective gas-liquid cyclone separator at a high flux density. Within the
      implementation of the project, the goal was to choose the schematic construction
      of the separator provides the reduced dynamic head of flow in the zones with
      increased liquid phase concentration to prevent the entrainment of separated
      liquid and layer losses. The paper presents the numerical simulation data and
      experimental data allowed estimation of separation efficiency of the separator.

PMID- 30294633
TI  - Data on fluoride contamination in potable water in alluvial plains of district
      Panipat, Haryana, India.
AB  - This data set reveals the fluoride concentration level of an alluvial aquifer of
      Panipat district Haryana India. The whole district of Panipat relies on
      groundwater for its agricultural, industrial and domestic purposes. Fluoride
      concentration in the study area varied from 0.5 mg/L to 5.95 mg/L with an average
      of 1.6 mg/L. 42.9% of the groundwater samples have shown higher fluoride
      concentration in groundwater than the permissible level prescribed by World
      Health Organisation and Bureau of Indian Standards. The spatial distribution map
      of fluoride has interestingly shown contrast between western and eastern parts of
      the region. Higher fluoride concentration (1.00-5.95 mg/L) in groundwater is
      witnessed in western half whereas the eastern half had comparatively lower
      concentration of fluoride ranging from 0.5 mg/L to 3.0 mg/L with maximum area
      having concentrations up to 1.5 mg/L. Major part 52.23% of Panipat district has
      shown high fluoride concentration in groundwater than the permissible level. It
      is further suggested that prolonged intake of groundwater with fluoride
      concentration higher than the permissible levels may cause dental or skeletal
      fluorosis in the locals.

PMID- 30294634
TI  - Dataset on customer experience and satisfaction in healthcare sector of Nigeria.
AB  - The central aim of the study was to show a dataset that empirically examines the
      connection between customer experience (CE) and customer satisfaction (CS). Few
      or no research have investigated how customer experience can be used to improve
      customer satisfaction in the healthcare sector of Nigeria. The study therefore
      adopted a survey research and the data were generated via a structured
      questionnaire. A total of 365 copies of the questionnaire were retrieved from the
      customers of the selected four private hospitals in Lagos State. The
      questionnaire administered were analysed using SPSS (version 22). Using the
      descriptive and the Categorical Regression CATREG analysis, the data explained
      how customer experience have a significant relationship with customer
      satisfaction. The data gathered is provided openly so as to facilitate further
      analysis.

PMID- 30294635
TI  - Data sets of eQTL loci, correlation analysis, and overlapped genes among gene
      sets that their expression levels are closely related to genes of Vegf family.
AB  - This data is generated from the analysis of similarities and differences in gene
      expression levels and pathways among genes (VegfA, VegfB, VegfC, and Pgf) in Vegf
      family using whole genome expression data generated from normal retina of eighty
      strains of mice. The results have been published in
      doi:10.1016/j.exer.2018.06.024 (Cui et al., 2018) [1]. Fig. 1 shows the
      expression quantitative trait loci (eQTL) that regulate the expression level of
      each gene in the Vegf family. The other three figure show the overlapped genes
      among the top 500 genes that their expression levels are most closely correlated
      to each of the Vegf genes. The four tables contain the information of top 50
      genes that their expression levels are most closely correlated to each of the
      Vegf genes, and the correlation of the top 50 genes from one gene to the other
      genes in the Vegf family.

PMID- 30294636
TI  - Quantitative proteome of midgut, Malpighian tubules, ovaries and fat body from
      sugar-fed adult An. stephensi mosquitoes.
AB  - The data presented in this article is associated with the quantitative proteomic
      analysis of four mosquito tissues - midgut, Malpighian tubules, ovaries and fat
      body from female Anopheles stephensi mosquitoes. To identify the proteins that
      were expressed in a tissue-specific manner, the four mosquito tissues were
      labelled with iTRAQ labels and analyzed using a high-resolution mass
      spectrometer. Database searches of the 1,10,616 raw spectra from 23 peptide
      fractions resulted in the identification of 84,733 peptide spectrum matches
      corresponding to 16,278 peptides and 3372 proteins. Of these, 959 proteins were
      found to be differentially expressed across the tissues. Gene ontology-based
      bioinformatic analysis of the differentially expressed proteins are also provided
      in the article. The data in this article has been deposited in the
      (ProteomeXchange) Consortium via the PRIDE repository and can be accessed through
      the accession ID, PXD001128.

PMID- 30294637
TI  - Data on electronic structures for the study of ligand effects on the zirconocene
      mediated trimethylene carbonate polymerization.
AB  - The data presented in this paper are related to the research article entitled
      "Effect of ligand structure in the trimethylene carbonate polymerization by
      cationic zirconocene catalysts: A "naked model" DFT study" (Jitonnom and Meelua,
      2017) [1]. In this data article, we present 3D molecular information of 29
      zirconocene catalysts that differ in electronic and steric properties. The data
      contains all cationic species along the initiation and first propagation step of
      the polymerization, which are provided in a PDB format that can be used for
      further studies.

PMID- 30294638
TI  - Dataset on the expression level of the genes involved in the synthesis of
      structural molecules in carbon-deficient microalgae.
AB  - The data presented in this article are related to the research article entitled
      "Bicarbonate-rich wastewater as a carbon fertilizer for culture of
      Dictyosphaerium sp. of a giant pyrenoid" (Cheng et al., 2018) [1]. This article
      provides data about the expression levels of the genes involved in the synthesis
      of structural molecules in the carbon-deficient algal cell and the carbon-treated
      algal cell, which can be helpful for analyzing the observed disruption of the
      structural integrity in the carbon-deficient microalgae at molecular level.

PMID- 30294639
TI  - Data on COA-Cl administration to the APP/PS2 double-transgenic mouse model of
      Alzheimer's disease: Improved hippocampus-dependent learning and unchanged
      spontaneous physical activity.
AB  - We herein present behavioral data regarding whether COA-Cl, a novel adenosine
      like nucleic acid analog that promotes angiogenesis and features neuroprotective
      roles, improves cognitive and behavioral deficits in a murine model for
      Alzheimer's disease (AD). COA-Cl induced significant spatial memory improvement
      in the amyloid precursor protein/presenilin 2 double-transgenic mouse model of AD
      (PS2Tg2576 mice). Correspondingly, non-spatial novel object cognition test
      performance also significantly improved in COA-Cl-treated PS2Tg2576 mice;
      however, these mice demonstrated no significant changes in physical activity or
      motor performance. COA-Cl did not change the spontaneous activities and cognitive
      ability in the wild-type mice.

PMID- 30294640
TI  - Data on accessibility of corporate information and business transparency in
      Russia.
AB  - Empirically based, the data description covers business transparency in Russia
      and availability of corporate information for interested parties. Entry barriers
      in the form of a fee for hard copies of documents are perceptible as an important
      indicator of business publicity. The study made it possible to summarize current
      data on 5070 Russian enterprises in order to estimate document copying cost
      differentiation according to the developed model. The sample size made it also
      possible to ensure high levels of data quality and representativeness. Actual
      limiting average mean error Deltap was 3.47% with 99% of study validity. The
      analysis relied on regional and sectorial data groupings to show a strength of
      various impact factors. In view of this, correlation coefficients, average and
      weighted average cost values, and descriptive statistics became secondary
      indicators. The cost value distributed along an interval scale is a major
      empirical result of the research. The examination of the obtained data makes it
      possible to identify an availability level of corporate information for various
      stakeholders and the general public. This is a part of civil right enforcement in
      the field of information control and validity check. Conjugated scientific issues
      include pricing of non-core services of companies, corporate relations and
      modelling of market behaviours. By making a representative data set, authors make
      an effort to fill the fact-based gap available in other disciplines and related
      to business transparency in Russia.

PMID- 30294641
TI  - Sensitivity to imatinib of KCL22 chronic myeloid leukemia cell survival/growth
      and stem cell potential under glucose shortage.
AB  - The data presented here are related to the original research article entitled
      "Imatinib enhances the maintenance of Chronic Myeloid Leukemia (CML) stem cell
      potential in the absence of glucose" (Bono et al., 2018). The sensitivity to the
      tyrosine kinase inhibitor imatinib-mesylate (IM) of KCL22 CML cells cultured
      under glucose shortage have been determined by scoring cell survival/growth via
      trypan blue exclusion and stem cell potential via Culture Repopulation Ability
      (CRA) assay. Discussion of the data can be found in Bono et al. (2018).

PMID- 30294642
TI  - PM10 Plume dispersion data of the Zouk power plant in Lebanon.
AB  - Ambient air pollution is a major risk to the human health and to the environment.
      The data presented quantifies the (PM10) contribution of the Zouk Mikael power
      plant to the ambient air pollution in Lebanon for the year 2014. The data is the
      outcome of a computer simulation using The Air Pollution Model (TAPM), taking
      into account the emission source data, the spatio-temporal meteorological
      conditions, the terrain height, and the land cover characteristics. The data set
      presents the annual, seasonal and monthly averages of the spatial distribution of
      the ground-level particulate (PM10) concentrations in the ambient air. The data
      set also includes spatial distribution of the maximum concentrations, which
      revealed two zones of elevated concentrations. Monthly averages and maximum
      concentrations in these two zones are also reported. Analysis of the data can
      provide information on the health risk the residents in the affected areas are
      subjected to. The data can also provide insight on the impact of the
      meteorological conditions (temperature and velocity) and the topography on
      pollutant dispersion in regions bounded by the sea and by a mountain range.

PMID- 30294643
TI  - Crystallographic home-source X-ray data for the atomic-resolution experimental
      phasing of the Shank3 SH3 domain structure from pseudomerohedrally twinned
      crystals.
AB  - By far most macromolecular crystallographic data collection and experimental
      phasing is nowadays carried out using synchrotron radiation. Here, we present two
      crystallographic datasets collected on a home-source X-ray diffractometer, which
      can per se be use to experimentally solve the atomic-resolution crystal structure
      of the Src homology 3(SH3)-like domain from the postsynaptic protein Shank3. The
      refined structure was described in the article "Structure of an unconventional
      SH3 domain from the postsynaptic density protein Shank3 at ultrahigh resolution"
      (Ponna et al., 2017) [1]. Crystals of the Shank3 SH3 domain were derivatized
      through soaking in 1 M sodium iodide prior to diffraction data collection at a
      wavelength of 1.54 A. High-resolution data are reported for a native crystal to
      1.01 A and an iodide-derivatized one to 1.60 A. The crystals suffered from
      several anomalies affecting experimental phasing: a high fraction (34-40%) of
      pseudomerohedral twinning, significant pseudotranslational symmetry (> 15%) with
      the operator 0.5,0,0.5, and a low solvent content. Twinning with the operator h,
      k,-l is made possible by the space group P21 coupled with a unit cell beta angle
      of 90.0 degrees . The data can be used to repeat and optimize derivatization and
      phasing procedures, to understand halide interactions with protein surfaces, to
      promote the use of home X-ray sources for protein structure determination, as
      well as for educational purposes and protocol development.

PMID- 30294644
TI  - Data on evaluation of AQI for different season in Kerman, Iran, 2015.
AB  - The purpose of this data, was to evaluate the air quality index of Kerman city in
      different season of 2015. The data showed that the PM10 and O3 were highest in
      the winter season and PM2.5, CO, SO2 and NO2 in the spring season as the air
      quality indexes. The highest number of unhealthy days was observed in spring in
      relation to PM2.5 and PM10 pollutants. The data showed that 33 and 9 days of the
      spring season had unfavorable conditions in relation PM2.5 and PM10 pollutants
      respectively. Therefore, the pollutant responsible for air pollution in Kerman
      was PM2.5. By comparing the air quality index in different seasons of 2015 in
      terms of different pollutants, it was found that in most of the seasons, Kerman
      has a desirable air quality index.

PMID- 30294645
TI  - Consumer perception data and scientific arguments about food packaging
      functionalities for fresh strawberries.
AB  - This data article contains data characterizing consumer perception and scientific
      arguments about food packaging functionalities for fresh strawberries. These data
      are associated with the article "Choice of environment-friendly food packagings
      through argumentation systems and preferences" (see Yun et al., 2018). These data
      are stored in a public repository structured by an ontology. These data could be
      retrieved through the @Web tool, user-friendly interface to capitalize and query
      data (Buche et al., 2013; Guillard et al., 2017). The @Web tool is accessible
      online at http://pfl.grignon.inra.fr/atWeb/.

PMID- 30294646
TI  - Structural data of lanthanide complex constructed by 4-iodo-3-methyl benzoic acid
      and 4,7-dimethyl-1,10-phenanthroline.
AB  - In this data article, we present the FT-IR and PXRD data of the lanthanide
      complexes constructed by 4-iodo-3-methylbenzoic acid (IMBA) and 4,7-dimethyl-1,10
      phenanthroline (dmp). Detailed structure analysis, luminescence and sensing
      properties were discussed in our previous study, "Highly Luminescent Lanthanide
      Complexes as Bifunctional Sensor for Et2O and Fe2+" (Zhao et al., 2018). Also,
      the data include the bond lengths and angles of [Ln2(IMBA)6(dmp)2] (Ln=Eu3+, 1a;
      Ln=Gd3+, 1b; Ln=Tb3+, 1c).

PMID- 30294647
TI  - Inventory data on Brazilian Amazon's non-wood native biomass sources for
      bioenergy production.
AB  - This data article presents a set of non-wood native biomass sources identified
      for bioenergy production in isolated communities living in Amazon's extractive
      reserves. The data were inventoried using management plan documentation, which
      provides technical information on Amazon's protected areas. The sample was
      collected from a virtual database published by the Ministry of Environment, the
      federal body responsible for managing protected areas in Brazil. Five variables
      were extracted from the management plans to produce the inventory, which includes
      data on biomass typology, nomenclature and occurrence, as well as mode of access
      to communities and availability of energy sources in the protected areas.

PMID- 30294648
TI  - Data for efficiency comparison of raw pumice and manganese-modified pumice for
      removal phenol from aqueous environments-Application of response surface
      methodology.
AB  - Present deadest collection was aimed to evaluate the efficiency of raw pumice
      (RWP) and Mn-modified pumice (MMP). Response surface methodology (RSM) based on
      the central composite designs (CCD) was applied to evaluate the effects of
      independent variables including pH, adsorbents dosage, contact time and adsorbate
      concentration on the response function and the best response values were
      predicted. The Fourier transform infrared spectroscopy (FTIR), X-ray diffraction
      (XRD) and scanning electron microscopy (SEM) were used to characterize the
      adsorbents. Based on acquired data, the maximum efficiency removal of phenol was
      obtained 89.14% and 100% for raw and Mn-modified pumice respectively. The
      obtained data showed pH was effective parameter on phenol removal among the
      different variables. Evaluation of data using isotherms and kinetics models
      showed the fitted with Langmuir isotherm and pseudo second order kinetic for both
      adsorbents. According to obtained data was observed that modification of pumice
      can improve the efficiency removal of phenol to meet the effluent standards.

PMID- 30294649
TI  - Dataset for assessing the professional ethics of teaching by medical teachers
      from the perspective of students in Kermanshah University of Medical Sciences,
      Iran (2017).
AB  - The present data article was prepared with the aim of assessing the instructor's
      professional ethics of teaching in Kermanshah Medical Science University from the
      student's perspective in 2017. For this data article, 260 students in Kermanshah
      University of Medical Sciences (KUMS) were selected by a simple random sampling
      method. The data collection tool was based on "Ethical principles for college and
      university teaching" (Murray et al., 1996), teaching professional ethics
      questionnaire. The obtained data showed that the teachers have an average of
      (3.74 +/- 0.73) in terms of personality characteristic, (3.48 +/- 0.75) for
      dominating on content, (3.64 +/- 0.64) in terms of dominating on teaching
      practices, (3.65 +/- 0.63) for understanding the different learner's aspects,
      (3.65 +/- 0.71) in terms of teaching assessment and 4.41 +/- 0.78 for observing
      the educational regulations. These evaluated data were higher than the average
      level. The acquired data have shown that the instructors teaching professional
      ethic were higher than the average level, but still it was not ideal. Therefore,
      preparing and editing the teaching professional ethics charter and putting it in
      educational content during the teacher's service are suggested for the promotion
      of this status.

PMID- 30294650
TI  - Experimental data on the splitting tensile strength of bamboo reinforced
      lateritic concrete using different culm sizes.
AB  - In this data article, the splitting tensile strengths of bamboo reinforced
      lateritic concrete with varying bamboo culm sizes are presented and compared with
      bamboo reinforced pure concrete (i.e. no lateritic replacement for fine
      aggregate). 25% of fine aggregate was replaced with laterite and concrete
      cylinders were cast using bamboo reinforcements both full culm sizes and half
      culm sizes. The cylinders of 300 mm height and 150 mm diameter were cured for 28
      days and subjected to splitting tensile load at 7 days, 14 days and 28 days.
      Three samples were tested for each conditions and the average value computed.

PMID- 30294651
TI  - Data on B cell phenotypes in baboons with pig artery patch grafts receiving
      conventional immunosuppressive therapy.
AB  - This report is related to the research article entitled "B cell phenotypes in
      baboons with pig artery patch grafts receiving conventional immunosuppressive
      therapy" (Yamamoto et al., in press). Herein we provide the data regarding pig
      artery patch xenotransplantation into the baboon's aorta, trough levels of
      tacrolimus and rapamycin in the blood after transplantation, analysis of B cell
      phenotype on the basis of IgD and CD27 expression in the blood, and analysis of T
      cell phenotype on the basis of CD28 and CD95 expression in the blood.

PMID- 30294652
TI  - Data sets on delineation of groundwater potential zones identified by geospatial
      tool in Gudur area, Nellore district, Andhra Pradesh, India.
AB  - The data deals with the preparation of the groundwater potential zone map of
      gudur area, with the help of data like geology and geomorphology,
      structure/lineament, slope and drainage and the thematic layer were prepared
      through the Survey of India toposheet Nos. N/12,N/15,N/16 and IRS-P6 LISS
      III(RESOURCESAT-2) satellite data. The groundwater potential zones were obtained
      and classified into four categories, viz., very poor, poor, good, and very good
      zones. The data explains lateritic plain moderate basement with poor potential
      zones whereas secondarily occupies alluvial plain contains the good prospecting
      zone.

PMID- 30294654
TI  - Keratotic papules in an annular arrangement.

PMID- 30294655
TI  - Verrucous plaques on the nose and palate.

PMID- 30294656
TI  - Mullerian carcinosarcoma in the colon of a patient with history of endometrial
      carcinoma: A case report and insight into possible pathogenesis.
AB  - *Mullerian carcinosarcoma can occur in extragenital sites.*Malignant
      transformation of endometriosis is common in the rectosigmoid area.*MLH1
      hypermethylation has been implicated in endometriosis-associated
      carcinomas.*Adequate sampling is essential in determining the etiology of colonic
      tumors.

PMID- 30294653
TI  - Micronutrients in Nonalcoholic Fatty Liver Disease Pathogenesis.
AB  - Micronutrients include electrolytes, minerals, vitamins, and carotenoids, and are
      required in microgram or milligram quantities for cellular metabolism. The liver
      plays an important role in micronutrient metabolism and this metabolism often is
      altered in chronic liver diseases. Here, we review how the liver contributes to
      micronutrient metabolism; how impaired micronutrient metabolism may be involved
      in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a systemic
      disorder of energy, glucose, and lipid homeostasis; and how insights gained from
      micronutrient biology have informed NAFLD therapeutics. Finally, we highlight
      some of the challenges and opportunities that remain with investigating the
      contribution of micronutrients to NAFLD pathology and suggest strategies to
      incorporate our understanding into the care of NAFLD patients.

PMID- 30294657
TI  - Measuring social inequality in health amongst indigenous peoples in the Arctic. A
      comparison of different indicators of social disparity among the Inuit in
      Greenland.
AB  - The purpose of the article is to compare different indicators of social position
      as measures of social inequality in health in a population sample from an
      indigenous arctic people, the Inuit in Greenland. Data was collected during 2005
      2015 and consisted of information from 3967 adult Inuit from towns and villages
      in all parts of Greenland. Social inequalities for smoking and central obesity
      were analysed in relation to seven indicators of social disparity in four
      dimensions, i.e. education and employment, economic status, sociocultural
      position, and place of residence. For each indicator we calculated age-adjusted
      prevalence by social group, rate ratio and the concentration index. The
      indicators were correlated with Pearson's r ranging from 0.24 to 0.82.
      Concentration indices ranged from 0.01 to 0.17. We could not conclude that one
      indicator was superior to others. Most of the indicators were traditional
      socioeconomic indicators used extensively in research in western countries and
      these seemed to be useful among the Inuit too, in particular household assets and
      job. Two sociocultural indicators developed for use among the Inuit and which
      included parameters specific to the indigenous peoples in the transition from a
      traditional to a modern life style proved to be equally useful but not superior
      to the traditional socioeconomic indicators. The choice of indicator must depend
      on what it is realistic to collect in the actual research setting and the use of
      more than one indicator is recommended. It is suggested to further develop
      culture specific indicators of social position for indigenous peoples.

PMID- 30294658
TI  - Interlaboratory validation of cerebrospinal fluid alpha-synuclein quantification
      in the diagnosis of sporadic Creutzfeldt-Jakob disease.
AB  - Introduction: Cerebrospinal fluid alpha-synuclein level is increased in sporadic
      Creutzfeldt-Jakob disease cases. However, the clinical value of this biomarker
      remains to be established. In this study, we have addressed the clinical
      validation parameters and the interlaboratory reproducibility by using an
      electrochemiluminescent assay. Methods: Cerebrospinal fluid alpha-synuclein was
      quantified in a total of 188 sporadic Creutzfeldt-Jakob disease and non
      Creutzfeldt-Jakob-disease cases to determine sensitivity and specificity values
      and lot-to-lot variability. Two round robin tests with 70 additional cases were
      performed in six independent laboratories. Results: A sensitivity of 93% and a
      specificity of 96% were achieved in discriminating sporadic Creutzfeldt-Jakob
      disease. No differences were detected between lots. The mean interlaboratory
      coefficient of variation was 23%, and the intralaboratory coefficient of
      variations ranged 2.70%-11.39%. Overall, 97% of samples were correctly diagnosed.
      Discussion: The herein validated alpha-synuclein assay is robust, accurate, and
      reproducible in identifying Creutzfeldt-Jakob disease cases. Thus, it is ready
      for implementation in the clinical practice to support the diagnosis of
      Creutzfeldt-Jakob disease.

PMID- 30294659
TI  - Network-based assessment of collaborative research in neuroscience.
AB  - Introduction: The purpose of this study was to describe collaborative research in
      neuroscience within the context of the Center for Neurodegeneration and
      Translational Neuroscience (CNTN), a Center of Biomedical Research Excellence
      supported by the National Institute of General Medical Science. Drawing upon
      research on the science of team science, this study investigated the way that
      interactions around research emerged over the course of establishing a new
      research center. The objectives were to document changes in research activity and
      describe how human research support infrastructure functioned to support the
      production of science. Methods: Social network analyses were used to model
      coauthorship relationships based on publication histories from baseline (2014)
      through the current grant year (2017) for key personnel (n = 12), as well as
      survey data on collaborative engagement among CNTN members (n = 59). Results:
      Exponential random graph models indicated that over time, CNTN members were
      increasingly likely to form coauthorship relationships. Community detection
      algorithms and brokerage analyses suggested that the CNTN was functioning as
      intended to support scientific development. Discussion: Assessment of team
      science efforts is critical to evaluating and developing appropriate support
      structures that facilitate successful team science efforts in translational
      neuroscience.

PMID- 30294660
TI  - Genetic associations of bradykinin type 2 receptor, alpha-adrenoceptors and
      endothelial nitric oxide synthase with blood pressure and left ventricular mass
      in outpatients without overt heart disease.
AB  - Background: Physiological pathways such as bradykinin, renin-angiotensin,
      neurohormones and nitric oxide have been shown to play an important role in the
      regulation of cardiovascular function. Genetic variants of these pathways may
      impact blood pressure and left ventricular (LV) mass in different populations. To
      evaluate associations of genetic polymorphisms of bradykinin B2 receptor
      (BDKRB2), alpha-adrenergic receptors (ADRA) and endothelial nitric oxide synthase
      (eNOS) on the modulation of the blood pressure and the left ventricular mass.
      Methods: We enrolled 758 individuals without overt heart disease. Blood pressure
      was estimated by auscultatory method during the clinical examination. Left
      ventricular (LV) mass was assessed by echocardiography. Genotypes for ADRA1A
      rs1048101, ADRA2A rs553668, ADRA2B rs28365031, eNOS rs2070744, eNOS rs1799983,
      and BDKRB2 rs5810761 polymorphisms were assessed by high-resolution melting
      analysis. Results: BDKRB2 polymorphism rs5810761 was associated with blood
      pressure. Carriers of DD genotype had higher levels of SBP and DBP than carrier
      of II genotype (p = 0.013 and p = 0.007, respectively). eNOS polymorphism
      rs1799983 was associated with DBP. Carriers of GT genotype had lower levels of
      DBP than carriers of GG genotype (p = 0.018). eNOS polymorphism rs2070744 was
      associated with LV mass. Carriers of TC genotype had higher LV mass than carriers
      of TT genotype (p = 0.028). Conclusions: In a cohort of individuals without overt
      heart disease, the BDKRB2 rs5810761 polymorphism (DD genotype carriers) were
      associated higher systolic and diastolic blood pressures, and the eNOS rs1799983
      polymorphism (T allele carriers) were associated with lower diastolic blood
      pressure. The eNOS rs2070744 polymorphism (C allele carriers) was associated with
      higher left ventricular mass. These data suggest that eNOS and bradykinin
      receptor genetic variants may be potential markers of common cardiovascular
      phenotypes.

PMID- 30294661
TI  - Knowledge of HIV and Intention to Engage in Risky Sexual Behaviour and Practices
      among Senior School Adolescents in Ibadan, Nigeria.
AB  - A high proportion of adolescents still engage in risky sexual behaviours that put
      them at risk of infection complications of risky sexual behaviours including
      Human Immunodeficiency Virus (HIV) infection despite the different interventions
      already in place. This study was designed to determine the adolescents' knowledge
      of HIV, intention to engage in risky sexual behaviour and sexual practices. A 3
      stage sampling technique was used to select 240 adolescents in senior secondary
      schools in Ibadan, Nigeria. Data were obtained using a pretested, semi
      structured, self-administered questionnaire. Data were analysed using descriptive
      statistics and Chi-square test at 5% level of significance. The mean age of the
      respondents was 16.3+/-1.4 years and 126(52.5%) were females. Only 34.3% had good
      knowledge of HIV and there were misconceptions about its transmission. Most of
      the respondents (95.0%) had intention to engage in risky sexual behaviour and
      those with good knowledge of HIV were willing to engage in risky sexual behavour
      with familiar people. Good knowledge was associated with intention to engage in
      low risk sexual behaviour. Seventy-nine (32.9%) were sexually active and they had
      better knowledge of HIV. Knowledge of HIV was low among this study group and was
      not associated with their intention to engage in risky sexual behaviour. There is
      need for more effective and appropriate school and community-based intervention
      programmes which can impact positively on the adolescents' sexual behaviour.

PMID- 30294662
TI  - Human Papilloma Virus Vaccine Awareness and Vaccination History in Patients
      Attending STI Clinics in Lagos and Ibadan, Nigeria.
AB  - HPV is one of the most common causes of sexually transmitted disease in both men
      and women worldwide. It is transmitted through vaginal, anal, and oral sex. This
      study provided information on the Human Papilloma Virus (HPV) vaccine awareness
      and vaccination history in relation to the level of antibodies to (HPV) in the
      population at risk in Nigeria. Patients attending STI clinics at Lagos and Ibadan
      were recruited and informed consent was obtained from all the participants. Using
      semi structured questionnaire, vaccination history, demography and past
      experiences of the patients were obtained. Whole blood samples were obtained and
      the sera screened for specific antibodies to HPV using ELISA test kits for
      determination of IgG to HPV by DIA PRO Diagnostic Bioprobes Milano-Italy
      according to the manufacturer's instruction. Of the170 samples analysed 50
      (29.4%) samples were positive for HPV. Thirty (17.6%) were from females and 20
      (11.7%) of them were males. Thirty-five (35%) of the 100 women participants were
      aware of HPV vaccine. 15(15%) women did not take the vaccine because they did not
      know where to get it while 20 (20%) of them could not afford it. It was also
      noted that there is higher prevalence among the middle-aged women. A high
      prevalence of HPV antibodies was observed in the study yet none of the
      participants had received the HPV vaccine thus the antibodies may be from
      infection. Implication is that the 30 women who tested positive for the HPV
      antibodies may be at risk of cervical cancer.

PMID- 30294663
TI  - Synthesis and preliminary preclinical evaluation of fluorine-18 labelled isatin-4
      (4-methoxyphenyl)-3-thiosemicarbazone ([18F]4FIMPTC) as a novel PET tracer of P
      glycoprotein expression.
AB  - Background: Several P-glycoprotein (P-gp) substrate tracers are available to
      assess P-gp function in vivo, but attempts to develop a tracer for measuring
      expression levels of P-gp have not been successful. Recently, (Z)-2-(5-fluoro-2
      oxoindolin-3-ylidene)-N-(4-methoxyphenyl)hydrazine-carbothioamide was described
      as a potential selective P-gp inhibitor that is not transported by P-gp.
      Therefore, the purpose of this study was to radiolabel two of its analogues and
      to assess their potential for imaging P-gp expression using PET. Results: [18F]2
      (4-fluoro-2-oxoindolin-3-ylidene)-N-(4-methoxyphenyl)hydrazine-carbothioamide
      ([18F]5) and [18F]2-(6-fluoro-2-oxoindolin-3-ylidene)-N-(4
      methoxyphenyl)hydrazine-carbothioamide ([18F]6) were synthesized and both their
      biodistribution and metabolism were evaluated in rats. In addition, PET scans
      were acquired in rats before and after tariquidar (P-gp inhibitor) administration
      as well as in P-gp knockout (KO) mice.Both [18F]5 and [18F]6 were synthesized in
      2-3% overall yield, and showed high brain uptake in ex vivo biodistribution
      studies. [18F]6 appeared to be metabolically unstable in vivo, while [18F]5
      showed moderate stability with limited uptake of radiolabelled metabolites in the
      brain. PET studies showed that transport of [18F]5 across the blood-brain barrier
      was not altered by pre-treatment with the P-gp inhibitor tariquidar, and uptake
      was significantly lower in P-gp KO than in wild-type animals and indeed
      transported across the BBB or bound to P-gp in endothelial cells. Conclusion: In
      conclusion, [18F]5 and [18F]6 were successfully and reproducibly synthesized,
      albeit with low radiochemical yields. [18F]5 appears to be a radiotracer that
      binds to P-gp, as showed in P-gp knock-out animals, but is not a substrate for P
      gp.

PMID- 30294664
TI  - Screw theory based mathematical modeling and kinematic analysis of a novel ankle
      rehabilitation robot with a constrained 3-PSP mechanism topology.
AB  - As a common athletics injury in orthopedics clinic, ankle injury may affect a
      person's daily life and ankle injury rehabilitation has gained increasing
      interests from the medical and robotic societies. A novel hybrid ankle
      rehabilitation robot is proposed, which composing of a serial and a parallel
      part. In order to analyze its kinematic performances, the parallel part of the
      robot is simplified as a constrained 3-PSP parallel mechanism. A mathematical
      model for the parallel part of the robot is established based on the screw
      theory. Then the inverse kinematics is obtained, and the reciprocal twists,
      Jacobian matrices and the singularity of the robot are analyzed. Finally the
      workspace of the central point on the moving platform is predicted. The kinematic
      analyses manifest that the proposed hybrid rehabilitation robot not only can
      realize three kinds of ankle rehabilitation motions, but also can eliminate
      singularity with enhanced workspace. The workspace of the central point reveals
      that the hybrid robot can fully meet the demanded rehabilitation space by
      comparing with the clinic demands. Our results reveals the characteristic
      structure of the hybrid rehabilitation robot and its superiority, it offers some
      basis data for the future enhancement of the device.

PMID- 30294665
TI  - ParaStamp and Its Applications to Cell Patterning, Drug Synergy Screening, and
      Rewritable Devices for Droplet Storage.
AB  - Engineered materials have been employed as versatile tools to explore the
      fundamental cell biology/drug development as well as to approach the intelligent
      device, thereby becoming the key components in modern technology. Herein, a
      ParaStamp technique has been revealed to possess applications for cell
      patterning, drug screening, and rewritable functional patterning. The ParaStamp
      includes a micropatterned PDMS master and a liquid-phased paraffin oil generated
      at high temperature, which can transfer the patterned paramembrane onto varied
      material surfaces, such as glass, polystyrene, and flexible foil. This technique
      is simple and cost-effective to meet the high-throughput requirement for
      industries. Taken together, our findings herein should have general insights in
      cell biology, biodetection, and development of smart hydrophobic surface.

PMID- 30294666
TI  - APOBEC3 Mediates Resistance to Oncolytic Viral Therapy.
AB  - Tumor cells frequently evade applied therapies through the accumulation of
      genomic mutations and rapid evolution. In the case of oncolytic virotherapy,
      understanding the mechanisms by which cancer cells develop resistance to
      infection and lysis is critical to the development of more effective viral-based
      platforms. Here, we identify APOBEC3 as an important factor that restricts the
      potency of oncolytic vesicular stomatitis virus (VSV). We show that VSV infection
      of B16 murine melanoma cells upregulated APOBEC3 in an IFN-beta-dependent manner,
      which was responsible for the evolution of virus-resistant cell populations and
      suggested that APOBEC3 expression promoted the acquisition of a virus-resistant
      phenotype. Knockdown of APOBEC3 in B16 cells diminished their capacity to develop
      resistance to VSV infection in vitro and enhanced the therapeutic effect of VSV
      in vivo. Similarly, overexpression of human APOBEC3B promoted the acquisition of
      resistance to oncolytic VSV both in vitro and in vivo. Finally, we demonstrate
      that APOBEC3B expression had a direct effect on the fitness of VSV, an RNA virus
      that has not previously been identified as restricted by APOBEC3B. This research
      identifies APOBEC3 enzymes as key players to target in order to improve the
      efficacy of viral or broader nucleic acid-based therapeutic platforms.

PMID- 30294667
TI  - miR-93 Promotes the Growth and Invasion of Prostate Cancer by Upregulating Its
      Target Genes TGFBR2, ITGB8, and LATS2.
AB  - This study aimed to evaluate the effects of miR-93 on the growth and invasiveness
      of prostate cancer (PC) cells (PCCs). Real-time PCR was carried out to detect the
      expression of miR-93 in the PC tissues and cell lines. The adjacent normal
      tissues served as controls. For in vitro experiments, methyl thiazolyl
      tetrazolium, clone formation, tumor cell invasion assays, and western blot
      analysis (WBA) were performed to confirm the variations in the proliferation and
      invasiveness of PCCs, prior and subsequent to transfection with an miR-93
      antisense oligonucleotide (ASO), which blocks miR-93 binding to its target.
      Furthermore, the effect of miR-93 on the proliferation of PCCs was examined.
      Finally, the expression levels of the target genes of miR-93 were determined by
      WBA. miR-93 expression was higher in PC tissues than in the adjacent normal
      tissues, and a reduction in the miR-93 level remarkably inhibited the
      proliferation and invasiveness of PCCs. Moreover, miR-93 enhanced the expression
      of its target genes TGFBetaR2, ITGB8, and LATS2. The results of this study
      suggest that miR-93 may promote the proliferation and invasion of PCCs by
      upregulating its target genes TGFBR2, ITGB8, and LATS2.

PMID- 30294668
TI  - Systematic Analysis of Transmitter Coexpression Reveals Organizing Principles of
      Local Interneuron Heterogeneity.
AB  - Broad neuronal classes are surprisingly heterogeneous across many parameters, and
      subclasses often exhibit partially overlapping traits including transmitter
      coexpression. However, the extent to which transmitter coexpression occurs in
      predictable, consistent patterns is unknown. Here, we demonstrate that pairwise
      coexpression of GABA and multiple neuropeptide families by olfactory local
      interneurons (LNs) of the moth Manduca sexta is highly heterogeneous, with a
      single LN capable of expressing neuropeptides from at least four peptide families
      and few instances in which neuropeptides are consistently coexpressed. Using
      computational modeling, we demonstrate that observed coexpression patterns cannot
      be explained by independent probabilities of expression of each neuropeptide. Our
      analyses point to three organizing principles that, once taken into
      consideration, allow replication of overall coexpression structure: (1)
      peptidergic neurons are highly likely to coexpress GABA; (2) expression
      probability of allatotropin depends on myoinhibitory peptide expression; and (3)
      the all-or-none coexpression patterns of tachykinin neurons with several other
      neuropeptides. For other peptide pairs, the presence of one peptide was not
      predictive of the presence of the other, and coexpression probability could be
      replicated by independent probabilities. The stochastic nature of these
      coexpression patterns highlights the heterogeneity of transmitter content among
      LNs and argues against clear-cut definition of subpopulation types based on the
      presence of single neuropeptides. Furthermore, the receptors for all
      neuropeptides and GABA were expressed within each population of principal neuron
      type in the antennal lobe (AL). Thus, activation of any given LN results in a
      dynamic cocktail of modulators that have the potential to influence every level
      of olfactory processing within the AL.

PMID- 30294669
TI  - Idiosyncratic, Retinotopic Bias in Face Identification Modulated by Familiarity.
AB  - The perception of gender and age of unfamiliar faces is reported to vary
      idiosyncratically across retinal locations such that, for example, the same
      androgynous face may appear to be male at one location but female at another.
      Here, we test spatial heterogeneity for the recognition of the identity of
      personally familiar faces in human participants. We found idiosyncratic biases
      that were stable within participants and that varied more across locations for
      low as compared to high familiar faces. These data suggest that like face gender
      and age, face identity is processed, in part, by independent populations of
      neurons monitoring restricted spatial regions and that the recognition responses
      vary for the same face across these different locations. Moreover, repeated and
      varied social interactions appear to lead to adjustments of these independent
      face recognition neurons so that the same familiar face is eventually more likely
      to elicit the same recognition response across widely separated visual field
      locations. We provide a mechanistic account of this reduced retinotopic bias
      based on computational simulations.

PMID- 30294671
TI  - Marijuana Induced Type I Brugada Pattern: A Case Report.
AB  - Marijuana is the most common drug of abuse in the United States. Marijuana acts
      on cannabinoid receptors CB1, CB2 and another distinct endothelial receptor.
      Marijuana is known to cause tachycardia, hypotension and hypertension. Various
      arrhythmias including atrial fibrillation, atrial flutter, II degree AV block,
      ventricular fibrillation, ventricular tachycardia, asystole and brugada pattern
      associated with marijuana use have been reported. We here present an interesting
      case of Type I Brugada pattern in electrocardiography (ECG) in a 36 year old
      healthy African American male who presented after smoking four joints. Urine
      toxicology test proved marijuana use. Acute coronary syndrome was ruled out,
      coronary angiogram revealed normal coronaries, 2D echocardiogram showed no
      evidence of structural heart disease. Upon resolution of Brugada pattern in ECG,
      procainamide challenge performed in electrophysiology laboratory did not induce
      Brugada pattern. Patient was asked to return to hospital if he developed fever
      that did not resolve with antipyretics. Further studies are required to to
      understand the effect of marijuana on cardiac ion channels.

PMID- 30294670
TI  - Cocaine Exposure Modulates Perineuronal Nets and Synaptic Excitability of Fast
      Spiking Interneurons in the Medial Prefrontal Cortex.
AB  - We previously reported that perineuronal nets (PNNs) are required for cocaine
      associated memories. Perineuronal nets are extracellular matrix that primarily
      surrounds parvalbumin (PV)-containing, GABAergic fast-spiking interneurons (FSIs)
      in the medial prefrontal cortex (mPFC). Here we measured the impact of acute (1
      d) or repeated (5 d) cocaine exposure on PNNs and PV cells within the prelimbic
      and infralimbic regions of the mPFC. Adult rats were exposed to 1 or 5 d of
      cocaine and stained for PNNs (using Wisteria floribunda agglutinin) and PV
      intensity 2 or 24 h later. In the prelimbic and infralimbic PFC, PNN staining
      intensity decreased 2 h after 1 d of cocaine exposure but increased after 5 d of
      cocaine exposure. Cocaine also produced changes in PV intensity, which generally
      lagged behind that of PNNs. In the prelimbic PFC, both 1 and 5 d of cocaine
      exposure increased GAD65/67 puncta near PNN-surrounded PV cells, with an increase
      in the GAD65/67-to-VGluT1 puncta ratio after 5 d of cocaine exposure. In the
      prelimbic PFC, slice electrophysiology studies in FSIs surrounded by PNNs
      revealed that both 1 and 5 d of cocaine exposure reduced the number of action
      potentials 2 h later. Synaptic changes demonstrated that 5 d of cocaine exposure
      increased the inhibition of FSIs, potentially reducing the inhibition of
      pyramidal neurons and contributing to their hyperexcitability during relapse
      behavior. These early and rapid responses to cocaine may alter the network
      stability of PV FSIs that partially mediate the persistent and chronic nature of
      drug addiction.

PMID- 30294672
TI  - A Rare Case of Second Degree Mobitz Type II AV Block Associated with Cocaine Use.
AB  - Cocaine is a commonly abused illicit drug in the United States. The complex
      effects of cocaine on the conduction system of the human heart has not been
      completely understood. Cocaine acts as a sympathomimetic by inhibition of
      reuptake of neuronal catecholamines, leading mostly to tachyarrhythmias on
      presentation. However, cocaine also exerts other effects on the conduction system
      including sympathomimetic, sino-bradycardic as well as local anesthetic
      properties. While Multiple cases of atrioventricular (AV) conduction blocks
      including first degree AV block, Mobitz type I and third degree AV blocks have
      been previously reported, we hereby present the first case report of cocaine-
      induced Mobitz type II second degree AV block. This case occurred in a 55 year
      old woman who presented with retrosternal chest pressure and tested positive for
      cocaine abuse as documented by urine toxicology test. Patient spontaneously
      converted to normal sinus rhythm the following day post admission to the
      hospital. Cocaine is known to inhibit sodium channels and thus has been known to
      decrease SA node automaticity and conduction via AV node. Electrophysiology
      studies have previously confirmed cocaine mediated delay in impulse conduction
      and repolarization. Though rare, physicians should be aware of the possibility of
      bradyarrhythmias associated with cocaine abuse in order to apply standard therapy
      such as pacemaker in the event of non-resolution of this serious arrhythmia.

PMID- 30294674
TI  - MT-CYB deletion in an encephalomyopathy with hyperintensity of middle cerebellar
      peduncles.

PMID- 30294673
TI  - Recurrent STEMI Precipitated by Marijuana Use: Case Report and Literature Review.
AB  - Marijuana abuse is rapidly growing and currently it is the most coimnon drug of
      abuse in the United States due to increased legalization for recreational and
      medicinal use. Delta 9-tetrahydrocannibol, the main psychoactive compound in
      marijuana, acts via the endocannabinoid system to elicit various cardiovascular
      physiological effects, and has been associated with many adverse cardiovascular
      effects such as acute coronary syndrome, arrhythmias, and sudden cardiac death
      that have previously been reported by our group and others. We present a case of
      a 30-year-old African-American male with no cardiovascular disease (CVD) risk
      factors with recurrent ST-segment elevation myocardial infarctions (STEMI) whose
      coronary angiography revealed recurrent 100% occlusion of the left anterior
      descending artery (LAD) in the setting of marijuana smoking. It was the patient's
      third STEMI with 100% occlusion of the LAD with each STEMI secondary to
      thrombosis of a different region of the LAD. Marijuana use was confirmed by urine
      toxicology screening at each STEMI presentation. Coronary angiography on multiple
      occasions was negative for stenosis of other epicardial coronary arteries, and
      coronary calcimn scoring was zero. Evaluation for other cardiovascular risk
      factors including family history of premature coronary artery disease,
      dyslipidemia, diabetes, and hypercoagulable disorders was negative. Further
      studies are required to elucidate the mechanisms of marijuana-associated coronary
      thrombosis and myocardial infarction.

PMID- 30294675
TI  - Necroptosis: MLKL Polymerization.
AB  - Necroptosis is a subtype of regulated necrosis that occurs when caspases are
      inhibited or fail to activate. Stimulus of cell death receptors results in a
      signaling cascade that triggers caspase independent, immunogenic cell death. The
      core pathway relies on receptor interacting protein kinase (RIPK) 1 and 3, which
      interact through their receptor homotypic interacting motif (RHIM) domains, and
      form amyloid-like structures termed the necrosome. RIPK3 recruits and
      phosphorylates mixed lineage kinase domain-like pseudokinase (MLKL), the terminal
      mediator in the necroptotic pathway. MLKL polymerizes to form a second amyloid
      like structure that causes cell membrane disruption resulting in cell death.
      Although the core necroptosis pathway has been elucidated, the details of MLKL
      membrane translocation and membrane disruption remain an open area of research.

PMID- 30294676
TI  - Selectivity and Specificity: Pros and Cons in Sensing.
AB  - Sensing using specific and selective receptors provides two very different but
      complementary strategies. This Sensor Issues article will discuss the merits and
      challenges of specific sensors, and selective sensors based on synthetic arrays.
      We will examine where each has been successfully applied to a sensing challenge,
      and then look at how a combined approach could take elements of both to provide
      new sensor platforms.

PMID- 30294677
TI  - Developing a framework for integrating health equity into the learning health
      system.
AB  - While there have been gains in the overall quality of health care, racial and
      ethnic disparities in health outcomes continue to persist in the United States.
      The Learning Health System (LHS) has the potential to significantly improve
      health care quality using patient-centered design, data analytics, and continuous
      improvement. To ensure that health disparities are also being addressed, targeted
      approaches must be used. This document sets forth a practical framework to
      incorporate health equity into a developing LHS. Using a case study approach, the
      framework is applied to 2 projects focused on the reduction of health disparities
      to highlight its application.

PMID- 30294678
TI  - Partial Deletion of the Long Arm of Chromosome 7: A Case Report.
AB  - Study advances with a childhood case of partial deletion of the long arm of
      chromosome 7. The patient is a 36-month-old girl with growth retardation, mild
      mental retardation and delayed bone age. She showed no signs of hypotelorism,
      upslanting palpebral fissures, epicanthal folds, low-set ears, or flat and broad
      nasal bridge. Microarray testing using the Affymetrix CytoScan HD array revealed
      an approximately 58 kb deletion at 7q31.1 in the girl and her father, suggesting
      paternal origin. As the patient had no characteristic facial features, 7q
      deletions had not been considered. This case broadens the range of case
      presentations for microdeletions of chromosome 7.

PMID- 30294679
TI  - Crystallization and initial X-ray diffraction analysis of the multi-domain
      Brucella blue light-activated histidine kinase LOV-HK in its illuminated state.
AB  - The pathogenic bacterium Brucella abortus codes for a multi-domain dimeric
      cytoplasmic histidine kinase called LOV-HK, which is a key blue light-activated
      virulence factor in this microorganism. The structural basis of the light
      activation mechanism of this protein remains unclear. In this work, full-length
      LOV-HK was cloned, expressed and purified. The protein was activated by light and
      crystallized under a controlled illumination environment. The merge of 14
      individual native data sets collected on a single crystal resulted in a complete
      X-ray diffraction data set to a resolution of 3.70 A with over 2 million
      reflections. Crystals belong to space group P212121, with unit-cell parameters a
      = 95.96, b = 105.30, c = 164.49 A with a dimer in the asymmetric unit. Molecular
      replacement with Phaser using the individual domains as search models allowed for
      the reconstruction of almost the whole protein. Very recently, improved LOV-HK
      crystals led to a 3.25-A resolution dataset. Refinement and model building is
      underway. This crystal model will represent one of the very few examples of a
      multi-domain histidine kinase with known structure.

PMID- 30294680
TI  - Soyasapogenols reduce cellular triglyceride levels in 3T3-L1 mouse adipocyte
      cells by accelerating triglyceride lipolysis.
AB  - Soyasapogenol is a soyasaponin aglycone, which has been suggested to exert a more
      potent function than the glycoside form. In this study, the effect of
      soyasapogenol A and B on cultured adipocyte cell function was investigated using
      mouse 3T3-L1 adipocyte cells. 3T3-L1 cells were treated with insulin,
      dexamethasone, and 3-isobutyl-1-methylxanthine for differentiation to adipocytes,
      and the cells were then cultured in the presence of soyasapogenol A or B (6.25 or
      12.5 uM). The media were harvested and refreshed every 2 d. After a 10 d culture,
      the cells were harvested and the triglyceride content of the cells was
      determined. The triglyceride content of soyasapogenol B-treated cells was
      significantly lower than those of vehicle-treated cells. Glycerol and free fatty
      acid levels in the soyasapogenol-treated cell media were higher than those in
      vehicle cells. However, there was no difference in the level of adipose
      triglyceride lipase among soyasapogenol A-, soyasapogenol B-, and vehicle-treated
      cells. The secreted adiponectin and resistin levels of soyasapogenol-treated cell
      media were also different compared with those of vehicle-treated cells.
      Especially, the secreted resistin level in soyasapogenol B-treated cell media was
      obviously reduced compared with that of vehicle-treated cells. Taken together,
      these results suggest that soyasapogenol B exerted an anti-obesity and anti
      diabetic effect on adipocytes by lowering the cellular triglyceride level by
      accelerating triglyceride lipolysis with reduced resistin secretion.

PMID- 30294682
TI  - Pharmacokinetics and safety/efficacy of levodopa pro-drug ONO-2160/carbidopa for
      Parkinson's disease.
AB  - We conducted a phase I study investigating the efficacy, safety, and tolerability
      of ONO-2160, a newly developed levodopa pro-drug, and carbidopa compared with
      levodopa and carbidopa to stabilize levodopa plasma concentration fluctuations in
      Japanese patients with Parkinson's disease. In an open-label two-period design,
      patients (n = 12) with Parkinson's disease received levodopa and carbidopa for 3
      days before 7 days of treatment with ONO-2160 and carbidopa. Patients were
      primarily evaluated using the Unified Parkinson's Disease Rating Scale Part III,
      a Parkinson's disease symptom diary, and analysis of adverse events.
      Pharmacokinetic analysis of plasma levodopa concentration was also performed. ONO
      2160 and carbidopa therapy stabilized effective plasma levodopa concentration. No
      adverse events with safety concerns were observed. The combination of ONO-2160
      and carbidopa produced a prolonged and stable plasma levodopa concentration with
      a reduction in Unified Parkinson's Disease Rating Scale Part III total scores.
      The combination was well tolerated, with no safety concerns, when administered to
      Japanese patients with Parkinson's disease.

PMID- 30294681
TI  - Potentials and challenges of diffusion-weighted magnetic resonance imaging in
      radiotherapy.
AB  - Purpose: To review the potential and challenges of integrating diffusion weighted
      magnetic resonance imaging (DWI) into radiotherapy (RT). Content: Details related
      to image acquisition of DWI for RT purposes are discussed, along with the
      challenges with respect to geometric accuracy and the robustness of quantitative
      parameter extraction. An overview of diffusion- and perfusion-related parameters
      derived from mono- and bi-exponential models is provided, and their role as
      potential RT biomarkers is discussed. Recent studies demonstrating potential of
      DWI in different tumor sites such as the head and neck, rectum, cervix, prostate,
      and brain, are reviewed in detail. Conclusion: DWI has shown promise for RT
      outcome prediction, response assessment, as well as for tumor delineation and
      characterization in several cancer types. Geometric and quantification robustness
      is challenging and has to be addressed adequately. Evaluation in larger clinical
      trials with well designed imaging protocol and advanced analysis models is needed
      to develop the optimal strategy for integrating DWI in RT.

PMID- 30294683
TI  - Surgical Treatment of Jejunal Artery Aneurysm.
AB  - Introduction: A jejunal artery aneurysm (JAA) is rare and has few specific
      symptoms. Endovascular repair is widely used in the treatment of jejunal artery
      aneurysms; however, some patients still require open repair. Report: A 59 year
      old man underwent open surgery with resection of the aneurysm and reconstruction
      using a saphenous vein graft. Histopathological examination revealed heterotopic
      pancreas around the aneurysm. Discussion: Inflammation as a result of heterotopic
      pancreas was suspected as the cause of JAA. The advantage of open repair is to
      explore intestinal ischaemia directly. Furthermore, revascularisation with a
      saphenous vein graft may remove the possibility of post-operative intestinal
      ischaemia.

PMID- 30294684
TI  - A Missing Posterior Division of the Internal Iliac Artery.
AB  - Introduction: To date, multiple variations in the pelvic vasculature have been
      reported. In this case report, a rare, so far unreported, branching anomaly of
      the internal iliac artery on the left side of a male human pelvis is described.
      Report: The complete posterior division of the internal iliac artery was shown to
      be missing on dissection of a 73 year old male cadaver. The iliolumbar artery,
      the lateral sacral arteries, and the superior gluteal artery originated
      unilaterally (on the left pelvis) directly from the common iliac artery.
      Discussion: No alteration was observed in the supplied structures of the left
      pelvic region, including the respective muscles, the sacrum, or the hip joint.

PMID- 30294685
TI  - Kindred spirits?
AB  - In this commentary, I reflect on the connections and strains between various
      efforts to expand options for family-making, to reduce the inequities that
      structure family-making through assisted reproduction and adoption, to secure and
      protect reproductive rights, and to pursue reproductive justice. I suggest that
      two threads connect these various aspects of reproductive politics: the
      commitment to self-determination, and an expanded understanding of kinship beyond
      the nuclear and the biological. These two themes stand in complicated tension -
      visible in debates over the ethics of surrogacy, for instance, and in the ways
      that queer family-making is facilitated, in part, by class and racial
      inequalities - that need to be confronted head-on. I conclude with some examples
      of what political kinship built around family justice can and does look like at
      the level of concrete action.

PMID- 30294686
TI  - Corrigendum to "Gunshot-wound dynamics model for John F. Kennedy assassination"
      [Heliyon 4 (2018) e00603].
AB  - [This corrects the article DOI: 10.1016/j.heliyon.2018.e00603.].

PMID- 30294687
TI  - Stem cell factor induces polarization of microglia to the neuroprotective
      phenotype in vitro.
AB  - Microglia are classified mainly into the M1 or M2 phenotypes, which evoke either
      proinflammatory or neuroprotective responses. Given the association of microglia
      with the pathogenesis of neuronal diseases, they are in focus as therapeutic
      targets for the treatment of such conditions. Stem cell factor (SCF) is a ligand
      for the c-kit receptor, one of the differentiation factors for bone marrow cells.
      In this study, characteristics of SCF-activated microglia and their effects on
      neurons were analyzed to investigate the therapeutic potential of SCF in neuronal
      diseases. SCF was found to induce proliferation, migration, and phagocytosis of
      microglia. In addition, SCF-derived microglia showed a neuroprotective phenotype
      expressing anti-inflammatory cytokines, growth factors, and M2 markers as
      compared to the phenotype shown by granulocyte macrophage-colony stimulating
      factor-derived microglia expressing inflammatory cytokines and M1 markers.
      Furthermore, supernatant medium from SCF-activated microglia enhanced cell
      proliferation and protection from cell death in NSC-34 neuronal cells. We
      conclude that SCF modulates microglial functions and induces activation of the
      neuroprotective effects of microglia, which could be used for treatment of
      neuronal diseases.

PMID- 30294688
TI  - Calcined magnesite as an adsorbent for cationic and anionic dyes:
      characterization, adsorption parameters, isotherms and kinetics study.
AB  - The ability of calcined magnesite for Methylene Blue (MB), Direct Red 81 (DR81),
      Methyl Orange (MO) and Crystal Violet (CV) dye removal was evaluated in this
      study. The experiments were designed to test the hypothesis that alkaline earth
      carbonates can remove dyes from water through a combination of sorption and
      coagulative reactions involving Mg2+. To achieve that, several operational
      factors like residence time, dosage, adsorbent concentration and temperature were
      appraised. The batch study proved that calcined magnesite is effective in the
      treatment of MB, DR81, CV and MO contaminated water and moreover it performed
      well in terms of color removal. The adsorption equilibrium data were analysed by
      the Langmuir, Freundlich, Dubinin-Radushkevich and Temkin isotherm models, and
      the Dubinin-Radushkevich and Temkin models were found to be the most appropriate
      fit to MB and MO dyes respectively. The adsorption kinetics process primarily
      followed the Elovich and Pseudo-second order model, a possible indication that
      chemisorption was the rate limiting step during the dye uptake process. With the
      adsorption-desorption cycle repeated four times, the calcined magnesite
      regeneration efficiency for DR81 and MO loaded dyes remained very high. According
      to the results of this study, it can be concluded that calcined magnesite can be
      used effectively for the adsorption of MB, DR81, CV and MO from wastewater.

PMID- 30294689
TI  - Unknown genes, Cebelin and Cebelin-like, predominantly expressed in mouse brain.
AB  - We identified two genes, Cebelin and Cebelin-like, encoding unknown proteins in
      mice. Cebelin and Cebelin-like consist of 168 and 167 amino acids with putative
      secreted signal sequences. However, Cebelin and Cebelin-like are cellular
      proteins not secreted proteins. Cebelin and Cebelin-like were predominantly
      expressed in the brain among major tissues examined. The expression of Cebelin in
      the brain was predominantly detected in the internal granule layer of the
      cerebellum.

PMID- 30294690
TI  - A first step towards a model for teachers' adoption of ICT pedagogy in schools.
AB  - It is important to identify and understand important factors underpinning the
      integration of information and communication technology (ICT) in schools. And, it
      is important that ICT is adopted in a sound pedagogical manner. The aim with this
      study was to suggest a model for the actual use of ICT in schools and how it may
      be related to important factors such as technological pedagogical expectations.
      The design of the model was inspired by TAM2 and UTAUT models, but with some
      modifications. We have developed a model which highlight the pedagogical aspects
      beyond the technical ones. Furthermore, our suggested model also include the
      adoption of digital techniques in everyday life as a potential predictor of
      adoption of ICT at work. The sample consists of 122 teachers and we analyzed the
      model with a structural equation model. This study contributes with a suggested
      model including a new construct for measuring expected performance from a
      technological pedagogical point of view. This new construct was a significant
      predictor to actual use of ICT in school. Furthermore we also developed a new
      construct for adoption of ICT in everyday life, which also was a significant
      predictor to actual use of ICT in school.

PMID- 30294691
TI  - Resilience through risk management: cooperative insurance in small-holder
      aquaculture systems.
AB  - Aquaculture is a booming industry. It currently supplies almost half of all fish
      and shellfish eaten today, and it continues to grow faster than any other food
      production sector. But it is immature relative to terrestrial crop and livestock
      sectors, and as a consequence it lags behind in terms of the use of aquaculture
      specific financial risk management tools. In particular, the use of insurance
      instruments to manage weather related losses is little used. In the aquaculture
      industry there is a need for new insurance products that achieve both financial
      gains, in terms of reduced production and revenue risk, and environmental wins,
      in terms of incentivizing improved management practices. Here, we have developed
      a cooperative form of indemnity insurance for application to small-holder
      aquaculture communities in developing nations. We use and advance the theory of
      risk pools, applying it to an aquaculture community in Myanmar, using empirical
      data recently collected from a comprehensive farm survey. These data were used to
      parameterize numerical simulations of this aquaculture system with and without a
      risk pool. Results highlight the benefits and costs of a risk pool, for various
      combinations of key parameters. This information reveals a path forward for
      creating new risk management products for aquaculturalists around the world.

PMID- 30294693
TI  - Reducing electric energy consumption in linear Fresnel collector solar fields
      coupled to thermal desalination plants by optimal mirror defocusing.
AB  - In many parts of the world, desalination is the only viable and economic solution
      to the problem of fresh water shortage. The current commercial desalination
      technologies rely on fossil fuels and are thus associated with high greenhouse
      gas emissions that are a major cause of climatic changes. Solar thermal-driven
      multi-effect distillation with thermal vapor compression is a clean alternative
      to conventional desalination technologies. To comprehend this process, as well as
      its features and limitations, extensive modeling is required. In this work, we
      proposed a plant design based on a solar field with a linear Fresnel collector
      that supplies heat to a multi-effect distillation plant with thermal vapor
      compression. The solar desalination plant model is implemented in the Engineering
      Equation Solver (EES). The system performance is investigated and a control
      strategy for reducing electric pumping is proposed. Results showed that 1 m2 of
      the solar field produces 8.5 m3 of distillate per year. The proposed control
      strategy resulted in a 40% reduction in electric pumping energy. Our results
      highlight the versatility of the linear Fresnel collector when coupled with
      thermal desalination.

PMID- 30294692
TI  - In vitro alpha-amylase, alpha-glucosidase, lipase inhibitory and cytotoxic
      activities of tuber extracts of Kedrostis africana (L.) Cogn.
AB  - Kedrostis africana, is a tuberous plant commonly used by traditional healers in
      the Eastern Cape Province of South Africa for the management of obesity. The aim
      of this study was to investigate the antiobesity and cytotoxic effects of
      Kedrostis africana extracts in vitro The alpha-amylase, alpha-glucosidase and
      lipase inhibitory activities of aqueous and ethanol extracts of Kedrostis
      africana tuber were investigated while the cytotoxic effects of these extracts
      were analyzed using Hoechst 33342 and propidium iodide (PI) dual staining in
      combination with Molecular Devices ImageXpress Micro XLS Widefield microscope for
      high content analysis on human cervical (HeLa) cell line. The ethanol extract
      exhibited the strongest inhibitory effect on pancreatic lipase (IC50 = 381.86
      MUg/ml) and on alpha-glucosidase (IC50 = 157.99 MUg/mL) while the aqueous extract
      has strongest alpha-amylase (IC50 = 439.45 MUg/ml). Both tuber extracts were
      found nontoxic at tested concentrations on HeLa cell lines as confirmed by the
      Hoechst 33342 and propidium iodide dual staining respectively. This study
      revealed that both the aqueous and ethanol tuber extract of K. africana exerts a
      certain degree of inhibitory effect on alpha-amylase, alpha-glucosidase and
      lipase and were also nontoxic to HeLa cell line at tested concentrations.

PMID- 30294694
TI  - An updated review on factors and their inter-linked influences on photovoltaic
      system performance.
AB  - Globally installed solar photovoltaics (PV) capacity has crossed three hundred
      gigawatts and is increasing each year. As the share of solar PV in the energy mix
      of a country increases, forecasting PV power available will be crucial. To
      forecast the instantaneous and long-term PV power output, understanding the
      factors influencing them is necessary. In this view, this work elaborates on the
      factors that impact the PV system through tabulation and graphical explanation.
      Further, a discussion of the articles related to the dust-induced change in
      performance is made. To understand the impact of dust on solar PV systems in
      depth, advanced instrumentation and methodologies have been used in the past few
      years. One of the methods is the measurement of spectral
      transmittance/reflectance/absorptance of the dust layer on the PV panel. This has
      led to the question whether a thin layer of some specific dust can be beneficial
      by absorbing infrared (IR) heat and hence allowing the PV cells to operate at a
      lower temperature. Many controlled experiments in the laboratory have been made
      using the artificial dust and sun simulators; and such studies aid in the
      development of numerical models. Research in modeling, mathematical analysis
      (from first principles) of dust deposition, and calculation of its impact on
      panels have been given importance in recent years. Outdoor experiments are
      relatively more common than other modes of research in this field. Studies
      involving the interaction of deposited dust with spectral radiation, improving
      the correlation between artificial and natural dust deposition, the interplay
      between dust and atmospheric parameters are to be encouraged.

PMID- 30294695
TI  - Investigation of the stable and unstable states of seismographs using poles and
      zeros pattern.
AB  - In this study, a simple Simulink model was designed and presented which can
      describe the overall operation of seismograph based on the desired input and
      output response. By converting Laplace to seismograph equations and by defining
      Numerator and Denominator fractions to Num. and Den. (Numerator and Denominator)
      transfer WWSSN (World-Wide Standard Seismographic Network) functions, the
      changeability of pole-zero was taken into consideration which indicates the
      stability and instability of the system layout with respect to pole - zero
      layout. In fact, the poles and zeros are placed in the seismograph response based
      on frequency, amplitude and phase (FAP) and are analyzed well. Through this
      method can also be used to study seismograph transfer function to predict the
      seismograph output in environments with different seismic noise and to select the
      most appropriate value for the parameters controlling the output of the device.

PMID- 30294697
TI  - Flavonoids and tannin composition of Bambara groundnut (Vigna subterranea) of
      Mpumalanga, South Africa.
AB  - Bambara groundnut (Vigna subterranea) an indigenous legume proclaimed to have
      medicinal properties within rural areas. Therefore, this study aimed to identify
      possible medicinal properties of Bambara groundnut (BGN). Flavonoids and tannins
      were highly concentrated in the red and brown BGN hulls. Among the flavonoid
      compounds rutin was observed in highest concentrations in brown hull (24.458 +/-
      0.234 mg g-1) and myricetin (1.800 +/- 0.771 mg g-1). While among tannin
      compounds chlorogenic acid was found in highest concentrations (0.115 +/- 0.199
      mg g-1) and ellagic acid in red hull (0.105 +/- 0.082 mg g-1). The form and
      colour of the BGN were all important factors to optimize the best extraction
      yield of phytochemicals. Overall the hulls of the BGN were the optimum source of
      flavonoids and tannins.

PMID- 30294696
TI  - Intermittent administration of a leucine-deprived diet is able to intervene in
      type 2 diabetes in db/db mice.
AB  - Continuous deficiency of leucine, a member of branched chain amino acids, is able
      to reduce obesity and improve insulin sensitivity in mice. Intermittent fasting
      has been shown to be effective in intervention of metabolic disorders including
      diabetes. However, it is unknown whether intermittent leucine deprivation can
      intervene in type 2 diabetes progression. We administered leucine-deprived food
      every other day in db/db mice, a type 2 diabetes model, for a total of eight
      weeks to investigate the interventional effect of intermittent leucine
      deprivation. Intermittent leucine deprivation significantly reduces hyperglycemia
      in db/db mice independent of body weight change, together with improvement in
      glucose tolerance and insulin sensitivity. The total area of pancreatic islets
      and beta cell number are increased by intermittent leucine deprivation,
      accompanied by elevated proliferation of beta cells. The expression level of
      Ngn3, a beta cell progenitor marker, is also increased by leucine-deleted diet.
      However, leucine deficiency engenders an increase in fat mass and a decrease in
      lean mass. Lipid accumulation in the liver is elevated and liver function is
      compromised by leucine deprivation. In addition, leucine deficiency alters the
      composition of gut microbiota. Leucine deprivation increases the genera of
      Bacteroides, Alloprevotella, Rikenellaceae while reduces Lachnospiraceae and
      these changes are correlated with fasting blood glucose levels of the mice.
      Collectively, our data demonstrated that intermittent leucine deprivation can
      intervene in the progression of type 2 diabetes in db/db mice. However, leucine
      deficiency reduces lean mass and aggravates hepatic steatosis in the mouse.

PMID- 30294698
TI  - Two-step recruitment process optimizes retention in FLEX clinical trial.
AB  - Introduction: The Flexible Lifestyle Empowering Change Study (FLEX) is a multi
      site randomized controlled trial to test the efficacy of an adaptive behavioral
      intervention to promote self-management and improve glycemic control for
      adolescents with type 1 diabetes mellitus. A two-step recruitment process was
      used to optimize study retention by facilitating informed decision-making
      regarding participation. Methods: Those who expressed interest at first contact
      were given more detailed study information followed by telephone calls to the
      adolescents and their parents to answer questions and explore potential barriers
      to participation before making a decision regarding study enrollment. Results: Of
      694 eligible adolescents who were invited to participate, 397 (57.2%) expressed
      interest when initially contacted (Step 1). Upon completion of the follow-up
      telephone calls (Step 2), 276 (39.8%) still agreed to participate; and 258
      (37.2%) enrolled and completed a baseline visit with a parent/guardian.
      Completion rates for measurement visits remained high throughout the study, with
      an end-of-study retention rate of 93.4%; and only 12 (4.7%) families withdrew
      from the study. Conclusion: The two-step recruitment process encourages potential
      participants to thoughtfully evaluate their willingness to participate, as well
      as their ability to make a commitment to the full completion of study
      requirements. When demonstrating the efficacy of a randomized controlled trial,
      it may be preferable to accept lower recruitment rates in order to optimize
      retention rates. The additional time and effort required to implement this two
      step process is worthwhile. With a high retention rate, we can be more confident
      that the outcomes of the randomized controlled trial actually reflect the impact
      of the intervention.

PMID- 30294699
TI  - Filipinos Fit and Trim - A feasible and efficacious DPP-based intervention trial.
AB  - Introduction: Filipino Americans are at higher risk for obesity and related Type
      2 diabetes (T2D) compared to other Asian subgroups and non-Hispanic whites. Yet,
      there are limited research studies to reduce health disparities and improve
      health outcomes for Filipinos. Weight loss lifestyle intervention trials such as
      the Diabetes Prevention Program (DPP) can reduce obesity and T2D risks through
      physical activity and healthy eating. Methods: Thus, we conducted a pilot
      Fit&Trim (DPP-based) intervention study - a randomized controlled trial 3-month
      intervention augmented with mobile technology + 3-month maintenance follow-up
      with a waitlist control. The objective assessed the intervention feasibility and
      potential efficacy to reduce T2D risks in Filipino Americans with
      overweight/obesity. The overall study goal was a mean 5% weight reduction.
      Results: Sixty-seven eligible Filipino men and women were enrolled and randomized
      to either an intervention or waitlist control group. Participant retention was
      91%. In Phase 1 (baseline to 3-months), the intervention group had greater weight
      reduction compared to the waitlist control (-4.3% vs. -0.88%; cross-level
      interaction = -0.85 (-1.4, -0.35). In Phase 2 (3- to 6-months), after receiving
      the Fit&Trim intervention, the waitlist group also had similar significant weight
      reduction [-4.8% (- 0.75 (-0.92, -0.58)]. A majority of intervention group (57%)
      also maintained their weight loss. Overall, 41% of study participants achieved a
      5% weight loss. Conclusion: The Fit&Trim intervention demonstrated feasibility
      and potential efficacy for Filipino Americans. Findings warrant a further larger,
      longer trial to test the Fit&Trim feasibility and effectiveness in a real-world
      Filipino community setting. ClinicalTrialsgov registration number: NCT02278939.

PMID- 30294701
TI  - Editorial: Bridging Scales and Levels.
AB  - Network neuroscience strives to understand the networks of the brain on all
      spatiotemporal scales and levels of observation. Current experimental and
      theoretical capabilities are beginning to facilitate a more holistic perspective,
      uniting these networks. This focus feature, "Bridging Scales and Levels," aims to
      document current research and looks to future progress towards this vision.

PMID- 30294700
TI  - Bilateral pseudo-internuclear ophthalmoplegia in a patient with myasthenia
      gravis.
AB  - Purpose: To report a case of myasthenia gravis presenting with a false localizing
      sign, a bilateral pseudo internuclear ophthalmoplegia. Observations: A 61 year
      old male presented with a five-week history of painless binocular oblique
      diplopia that was associated with fatigue, vocal hoarseness and bilateral ptosis,
      the latter two of which worsened through the course of the day. Exam was
      remarkable for an apparent bilateral internuclear ophthalmoplegia (INO). MRI of
      the brain with and without contrast and MRA of the head and neck were within
      normal limits. Lab work was positive for anti-AChR binding, blocking, and
      modulating antibodies, as well as anti-striated muscle and anti-titin antibodies.
      The patient was initiated on therapy for myasthenia gravis. Conclusion and
      importance: Although myasthenia gravis often presents with ptosis or diplopia,
      rarely patients may develop pseudo-INO secondary to extraocular muscle weakness.
      True INO occurs with damage to the medial longitudinal fasciculus, a myelinated
      tract of fibers that controls yoked horizontal eye movements. Clinicians should
      be suspicious of the false localizing sign of a pseudo-INO associated with
      myasthenia gravis when more common causes of INO have been excluded.

PMID- 30294702
TI  - Potential role of a ventral nerve cord central pattern generator in forward and
      backward locomotion in Caenorhabditis elegans.
AB  - C. elegans locomotes in an undulatory fashion, generating thrust by propagating
      dorsoventral bends along its body. Although central pattern generators (CPGs) are
      typically involved in animal locomotion, their presence in C. elegans has been
      questioned, mainly because there has been no evident circuit that supports
      intrinsic network oscillations. With a fully reconstructed connectome, the
      question of whether it is possible to have a CPG in the ventral nerve cord (VNC)
      of C. elegans can be answered through computational models. We modeled a
      repeating neural unit based on segmentation analysis of the connectome. We then
      used an evolutionary algorithm to determine the unknown physiological parameters
      of each neuron so as to match the features of the neural traces of the worm
      during forward and backward locomotion. We performed 1,000 evolutionary runs and
      consistently found configurations of the neural circuit that produced
      oscillations matching the main characteristic observed in experimental
      recordings. In addition to providing an existence proof for the possibility of a
      CPG in the VNC, we suggest a series of testable hypotheses about its operation.
      More generally, we show the feasibility and fruitfulness of a methodology to
      study behavior based on a connectome, in the absence of complete
      neurophysiological details.

PMID- 30294703
TI  - NeuroCave: A web-based immersive visualization platform for exploring connectome
      datasets.
AB  - We introduce NeuroCave, a novel immersive visualization system that facilitates
      the visual inspection of structural and functional connectome datasets. The
      representation of the human connectome as a graph enables neuroscientists to
      apply network-theoretic approaches in order to explore its complex
      characteristics. With NeuroCave, brain researchers can interact with the
      connectome-either in a standard desktop environment or while wearing portable
      virtual reality headsets (such as Oculus Rift, Samsung Gear, or Google Daydream
      VR platforms)-in any coordinate system or topological space, as well as cluster
      brain regions into different modules on-demand. Furthermore, a default side-by
      side layout enables simultaneous, synchronized manipulation in 3D, utilizing
      modern GPU hardware architecture, and facilitates comparison tasks across
      different subjects or diagnostic groups or longitudinally within the same
      subject. Visual clutter is mitigated using a state-of-the-art edge bundling
      technique and through an interactive layout strategy, while modular structure is
      optimally positioned in 3D exploiting mathematical properties of platonic solids.
      NeuroCave provides new functionality to support a range of analysis tasks not
      available in other visualization software platforms.

PMID- 30294704
TI  - Effect of different spatial normalization approaches on tractography and
      structural brain networks.
AB  - To facilitate the comparison of white matter morphologic connectivity across
      target populations, it is invaluable to map the data to a standardized
      neuroanatomical space. Here, we evaluated direct streamline normalization (DSN),
      where the warping was applied directly to the streamlines, with two publically
      available approaches that spatially normalize the diffusion data and then
      reconstruct the streamlines. Prior work has shown that streamlines generated
      after normalization from reoriented diffusion data do not reliably match the
      streamlines generated in native space. To test the impact of these different
      normalization methods on quantitative tractography measures, we compared the
      reproducibility of the resulting normalized connectivity matrices and network
      metrics with those originally obtained in native space. The two methods that
      reconstruct streamlines after normalization led to significant differences in
      network metrics with large to huge standardized effect sizes, reflecting a
      dramatic alteration of the same subject's native connectivity. In contrast, after
      normalizing with DSN we found no significant difference in network metrics
      compared with native space with only very small-to-small standardized effect
      sizes. DSN readily outperformed the other methods at preserving native space
      connectivity and introduced novel opportunities to define connectome networks
      without relying on gray matter parcellations.

PMID- 30294705
TI  - Catecholaminergic manipulation alters dynamic network topology across cognitive
      states.
AB  - The human brain is able to flexibly adapt its information processing capacity to
      meet a variety of cognitive challenges. Recent evidence suggests that this
      flexibility is reflected in the dynamic reorganization of the functional
      connectome. The ascending catecholaminergic arousal systems of the brain are a
      plausible candidate mechanism for driving alterations in network architecture,
      enabling efficient deployment of cognitive resources when the environment demands
      them. We tested this hypothesis by analyzing both resting-state and task-based
      fMRI data following the administration of atomoxetine, a noradrenaline reuptake
      inhibitor, compared with placebo, in two separate human fMRI studies. Our results
      demonstrate that the manipulation of central catecholamine levels leads to a
      reorganization of the functional connectome in a manner that is sensitive to
      ongoing cognitive demands.

PMID- 30294706
TI  - Frequency-based brain networks: From a multiplex framework to a full multilayer
      description.
AB  - We explore how to study dynamical interactions between brain regions by using
      functional multilayer networks whose layers represent different frequency bands
      at which a brain operates. Specifically, we investigate the consequences of
      considering the brain as (i) a multilayer network, in which all brain regions can
      interact with each other at different frequency bands; and as (ii) a multiplex
      network, in which interactions between different frequency bands are allowed only
      within each brain region and not between them. We study the second-smallest
      eigenvalue lambda 2 of the combinatorial supra-Laplacian matrix of both the
      multiplex and multilayer networks, as lambda 2 has been used previously as an
      indicator of network synchronizability and as a biomarker for several brain
      diseases. We show that the heterogeneity of interlayer edge weights and,
      especially, the fraction of missing edges crucially modify the value of lambda 2,
      and we illustrate our results with both synthetic network models and real data
      obtained from resting-state magnetoencephalography. Our work highlights the
      differences between using a multiplex approach and a full multilayer approach
      when studying frequency-based multilayer brain networks.

PMID- 30294707
TI  - Regions of Interest as nodes of dynamic functional brain networks.
AB  - The properties of functional brain networks strongly depend on how their nodes
      are chosen. Commonly, nodes are defined by Regions of Interest (ROIs),
      predetermined groupings of fMRI measurement voxels. Earlier, we demonstrated that
      the functional homogeneity of ROIs, captured by their spatial consistency, varies
      widely across ROIs in commonly used brain atlases. Here, we ask how ROIs behave
      as nodes of dynamic brain networks. To this end, we use two measures:
      spatiotemporal consistency measures changes in spatial consistency across time
      and network turnover quantifies the changes in the local network structure around
      an ROI. We find that spatial consistency varies non-uniformly in space and time,
      which is reflected in the variation of spatiotemporal consistency across ROIs.
      Furthermore, we see time-dependent changes in the network neighborhoods of the
      ROIs, reflected in high network turnover. Network turnover is nonuniformly
      distributed across ROIs: ROIs with high spatiotemporal consistency have low
      network turnover. Finally, we reveal that there is rich voxel-level correlation
      structure inside ROIs. Because the internal structure and the connectivity of
      ROIs vary in time, the common approach of using static node definitions may be
      surprisingly inaccurate. Therefore, network neuroscience would greatly benefit
      from node definition strategies tailored for dynamical networks.

PMID- 30294708
TI  - Changes in health-related quality of life and work-related outcomes for patients
      with mild-to-moderate ulcerative colitis receiving short-term and long-term
      treatment with multimatrix mesalamine: a prospective, open-label study.
AB  - Background: Ulcerative colitis (UC) is associated with lower health-related
      quality of life (HRQoL), and with disease activity predicting lower HRQoL and
      worse work-related outcomes. The current study examined the burden of UC on
      patients' HRQoL, as well as changes in patients' HRQoL and work-related outcomes
      following short-term and long-term treatment with multimatrix mesalamine, and
      their correspondence with changes in disease activity. Methods: Data were from an
      open-label, multinational, prospective trial (ClinicalTrials.gov identifier:
      NCT01124149) of 717 adults with active mild-to-moderate UC who were treated with
      4.8 g/day multimatrix mesalamine tablets once daily for eight weeks (acute
      phase). Four-hundred sixty-one patients who achieved partial or complete clinical
      and endoscopic remission subsequently received treatment with daily 2.4 g/day
      multimatrix mesalamine for 12 months (maintenance phase). At baseline, Week 8,
      and Month 12, patients were administered patient-reported outcomes (PRO) measures
      of HRQoL (the SF-12v2(r) Health Survey [SF-12v2] and Short Inflammatory Bowel
      Disease Questionnaire) and work-related outcomes (Work Productivity and Activity
      Impairment questionnaire, UC-specific version). SF-12v2 scores were compared to
      the U.S. general population using Analysis of Variance models to assess burden of
      UC on HRQoL. Mixed-effects repeated-measures models compared PRO scores across
      visits to assess change in PRO scores over time. Correlations examined the
      correspondence of changes in PRO scores with changes on a modified UC disease
      activity index (UC-DAI). Results: Baseline burden of disease observed on all SF
      12v2 domains was partially eliminated at Week 8 and completely eliminated at
      Month 12. Statistically significant improvements from baseline were observed at
      both Week 8 and Month 12 for all PRO scores (all P < 0.001). Decreases in UC-DAI
      scores significantly predicted improvements in PRO scores during the acute
      treatment phase. Conclusions: Patients with UC receiving daily multimatrix
      mesalamine treatment showed significant improvements in all measured domains of
      HRQoL and work-related outcomes. Patients who achieved partial or complete
      clinical and endoscopic remission maintained these improvements for most of these
      domains over 12 months with continued daily treatment. Changes in HRQoL and work
      related outcomes were inversely related to changes in disease activity. Findings
      support the effectiveness of multimatrix mesalamine for improving, and sustaining
      improvements, in HRQoL and work-related outcomes.

PMID- 30294709
TI  - The relationship between comorbidity medication adherence and health related
      quality of life among patients with cancer.
AB  - Background: Studies have demonstrated that comorbidities compound the adverse
      influence of cancer on health-related quality of life (HRQoL). Comorbidities
      adversely impact adherence to cancer treatment. Additionally, adherence to
      medications for comorbidities is positively associated with HRQoL for various
      diseases. This study used the Center for Disease Control and Prevention's Healthy
      Days measure of HRQoL to explore the association between HRQoL and adherence to
      comorbidity medication for elderly patients with cancer and at least one comorbid
      condition. Methods: We conducted a cross-sectional survey combined with
      retrospective claims data. Patients with metastatic breast, lung or colorectal
      cancer were surveyed regarding their HRQoL, comorbidity medication adherence and
      cancer-related symptoms. Patients reported the number of physical, mental and
      total unhealthy days in the prior month. The Morisky Medication Adherence 8-point
      scale was differentiated into moderate/high (> 6) and low (<= 6) comorbidity
      medication adherence. Results: Of the 1847 respondents, the mean age was 69.2
      years, most were female (66.8%) and the majority of the sample had Medicare
      coverage (88.2%). Low comorbidity medication adherence was associated with
      significantly more total, mental and physical unhealthy days. Low comorbidity
      medication adherence was associated with the presence of patient-reported cancer
      related symptoms. Patients reporting low, as compared to moderate/high,
      comorbidity medication adherence had 23.4% more unhealthy days in adjusted
      analysis, P = 0.007. Conclusion: The positive association between low comorbidity
      medication adherence and the number of unhealthy days suggests that addressing
      barriers to comorbidity medication adherence during cancer treatment may be an
      avenue for improving or maintaining HRQoL for older patients with cancer and
      comorbid conditions.

PMID- 30294710
TI  - Burden of renal angiomyolipomas associated with tuberous sclerosis complex:
      results of a patient and caregiver survey.
AB  - Background: Tuberous sclerosis complex (TSC) is a rare genetic disorder
      characterized by benign tumors in multiple organs, including non-cancerous kidney
      lesions known as renal angiomyolipomas. This study's objective is to describe the
      age-stratified morbidity, treatment patterns, and health-related quality of life
      of TSC patients with renal angiomyolipomas in the United States. A cross
      sectional, anonymous web-based survey was conducted with a convenience sample of
      TSC patients and caregivers identified through a patient advocacy organization.
      Results: Out of the total sample of 676, 182 respondents reported having kidney
      complications with 33% of the pediatric group and 25% of the adult group with TSC
      reporting them. Of those with kidney complications, 110 (60%) reported a
      diagnosis of renal angiomyolipomas, of which 79 (72%) were adult patients and 31
      (28%) were pediatric age patients. Eighty-four percent of the pediatric group and
      76% of the adult group reported lesions on both kidneys. Of the patients
      experiencing involvement of only one kidney, 60% of the pediatric group and 21%
      of the adult group reported having multiple tumors within the affected kidney.
      Almost all of the sample (99%) reported seeing a physician and having a procedure
      or test for TSC in the past year. Less than half the respondents (44%) reported
      being hospitalized in the past year. Thirty-nine percent reported an emergency
      room visit as well. Compared to scores for patients with kidney disease, the
      angiomyolipoma adult patients reported significantly lower Mental Component
      Summary scores on the SF-12. Conclusions: Renal angiomyolipomas burden leads to
      frequent healthcare resource use including hospitalization, invasive treatments,
      and surgical procedures, which result in an impaired mental health related
      quality of life.

PMID- 30294711
TI  - Measurement properties of the German version of the IKDC subjective knee form
      (IKDC-SKF).
AB  - Purpose: To examine the measurement properties of the German International Knee
      Documentation Committee Subjective Knee Form (IKDC-SKF) in knee disorder
      patients. Methods: Three hundred twelve consecutive patients undergoing surgery
      for anterior cruciate ligament, meniscus and/or cartilage injuries completed the
      IKDC-SKF, Lysholm Score, Tegner Activity Scale, and Short Form-12 Health Survey
      before and 6 months post-surgery. IKDC-SKF measurement properties were calculated
      and patients were also asked to rate the relevance/comprehensibility of the
      questionnaire items. Results: Reliability was good with high Cronbach's alpha and
      intraclass correlation coefficients, and standard error of measurement values of
      4.4 to 6.0. The smallest detectable change (SDC) ranged from 12.3 to 16.7 points.
      Validity was good with 90% of all hypotheses confirmed. Confirmatory factor
      analysis did not show adequate fitting indices within the model. Over half of the
      items were rated as essential, and all were well comprehended. The majority of
      hypotheses for responsiveness were confirmed. No floor and ceiling effects were
      observed. The area under the curve ranged from 0.82 to 0.89 and the minimal
      important difference was smaller than the SDC. Conclusions: The German IKDC-SKF
      is a reliable outcome measure with good hypotheses testing and responsiveness,
      but its MIC and structural/content validity need further analysis.

PMID- 30294713
TI  - Development of the Diabetes Injection Device Experience Questionnaire (DID-EQ)
      and Diabetes Injection Device Preference Questionnaire (DID-PQ).
AB  - Background: Previous research has examined patient perceptions of insulin
      injection devices. However, injectable medications other than insulin are
      increasingly used to treat type 2 diabetes, including GLP-1 receptor agonists. No
      patient-reported outcome (PRO) instruments have been developed taking into
      account the experiences of patients using newer injection devices, which are
      often different from devices used for insulin. Therefore, the purpose of this
      qualitative study was to develop two draft PRO instruments focusing on patients'
      experiences with these newer injection devices (one instrument assessing
      perceptions of a single injection device, and another assessing preferences
      between two devices). Methods: Questionnaire development proceeded in six steps:
      literature review, interviews with six device experts, concept elicitation
      interviews with patients (N = 32), preliminary translatability assessment,
      cognitive interviews with patients (N = 20), and final translatability
      assessment. Results: Literature review and expert interviews were conducted to
      inform a concept elicitation interview guide. In concept elicitation in the US,
      UK, and Germany, patients with type 2 diabetes reported a range of injection
      features that influenced their perceptions of non-insulin injection devices
      (e.g., requirements for preparation of the medication/device, issues related to
      the needle, ease-of-use, portability). Two draft "item pools" were developed
      based on the literature review, expert interviews, and concept elicitation
      results. In cognitive interviews, patients recommended minor revisions and
      indicated that the draft instruments were generally clear, comprehensible, and
      relevant to their experience with non-insulin injectable medication. The
      instruments were refined based on the cognitive interviews and translatability
      assessment, resulting in two questionnaires. Conclusions: The various steps of
      qualitative research support the content validity of these new PRO instruments,
      which are the first developed specifically to assess perceptions of non-insulin
      injection delivery systems. Despite some overlap with insulin-focused
      questionnaires, the new instruments are distinct from previous instruments
      (omitting content that would not be relevant to patients receiving non-insulin
      injectable treatment, while including content that is not included in the insulin
      focused instruments). This qualitative research yielded two draft questionnaires
      that are grounded in patient perceptions and ready for psychometric validation
      studies with larger samples of patients with type 2 diabetes.

PMID- 30294714
TI  - Psychometric evaluation of the Diabetes Injection Device Experience Questionnaire
      (DID-EQ) and Diabetes Injection Device Preference Questionnaire (DID-PQ).
AB  - Background: Previous research has examined patient perceptions of insulin
      injection devices. However, a range of injectable medications other than insulin
      are now used to treat type 2 diabetes. No patient-reported outcome (PRO)
      instruments have been developed taking into account the perceptions of patients
      using newer injection devices, which are often different from those used in the
      past. Therefore, the primary purpose of this study was to evaluate a new PRO
      instrument focusing on patients' experiences with injection devices, including
      those used for newer treatments such as GLP-1 receptor agonists. Methods:
      Patients with T2D treated with non-insulin injectable medications were recruited
      via advertisements and six clinical sites in the US. All participants completed
      the draft Diabetes Injection Device - Experience Questionnaire (DID-EQ) and
      additional measures administered for validity assessment. Participants who had
      experience with two non-insulin injection devices also completed the draft
      Diabetes Injection Device - Preference Questionnaire (DID-PQ). Analyses focused
      on item reduction (item performance, exploratory factor analysis), reliability,
      and validity. Results: One hundred fourty two patients (mean age = 63.0y; 56.3%
      female) participated. Item reduction yielded a 10-item version of the DID-EQ,
      including a 7-item Device Characteristics subscale and three global items
      assessing satisfaction, ease of use, and convenience of the injection device. The
      DID-EQ demonstrated good internal consistency reliability (Cronbach's alpha of
      Device Characteristics subscale = 0.80) and 7-day test-retest reliability (ICCs:
      0.92 for Device Characteristics subscale; 0.65 to 0.91 for the three global
      items). Construct validity was demonstrated via correlations with previously
      validated instruments (e.g., correlations with the DTSQ treatment satisfaction
      subscale ranged from 0.56 to 0.60, all p < 0.0001; correlations with the TRIM-D
      Device ranged from 0.63 to 0.77, all p < 0.0001). Descriptive analyses of the DID
      PQ were conducted with a subset of 27 participants who were able to use it to
      compare two devices. Conclusions: This psychometric evaluation supports the
      reliability and validity of the DID-EQ, while providing initial information on
      the performance of the DID-PQ. These brief questionnaires complement measures of
      treatment efficacy and provide a more thorough picture of patients' experiences
      with non-insulin injectable treatments for type 2 diabetes.

PMID- 30294712
TI  - How do patient reported outcome measures (PROMs) support clinician-patient
      communication and patient care? A realist synthesis.
AB  - Background: In this paper, we report the findings of a realist synthesis that
      aimed to understand how and in what circumstances patient reported outcome
      measures (PROMs) support patient-clinician communication and subsequent care
      processes and outcomes in clinical care. We tested two overarching programme
      theories: (1) PROMs completion prompts a process of self-reflection and supports
      patients to raise issues with clinicians and (2) PROMs scores raise clinicians'
      awareness of patients' problems and prompts discussion and action. We examined
      how the structure of the PROM and care context shaped the ways in which PROMs
      support clinician-patient communication and subsequent care processes. Results:
      PROMs completion prompts patients to reflect on their health and gives them
      permission to raise issues with clinicians. However, clinicians found
      standardised PROMs completion during patient assessments sometimes constrained
      rather than supported communication. In response, clinicians adapted their use of
      PROMs to render them compatible with the ongoing management of patient
      relationships. Individualised PROMs supported dialogue by enabling the patient to
      tell their story. In oncology, PROMs completion outside of the consultation
      enabled clinicians to identify problematic symptoms when the PROM acted as a
      substitute rather than addition to the clinical encounter and when the PROM
      focused on symptoms and side effects, rather than health related quality of life
      (HRQoL). Patients did not always feel it was appropriate to discuss emotional,
      functional or HRQoL issues with doctors and doctors did not perceive this was
      within their remit. Conclusions: This paper makes two important contributions to
      the literature. First, our findings show that PROMs completion is not a neutral
      act of information retrieval but can change how patients think about their
      condition. Second, our findings reveal that the ways in which clinicians use
      PROMs is shaped by their relationships with patients and professional roles and
      boundaries. Future research should examine how PROMs completion and feedback
      shapes and is influenced by the process of building relationships with patients,
      rather than just their impact on information exchange and decision making.

PMID- 30294715
TI  - Functional connectome of the five-factor model of personality.
AB  - A key objective of the emerging field of personality neuroscience is to link the
      great variety of the enduring dispositions of human behaviour with reliable
      markers of brain function. This can be achieved by analyzing large sets of data
      with methods that model whole-brain connectivity patterns. To meet these
      expectations, we exploited a large repository of personality and neuroimaging
      measures made publicly available via the Human Connectome Project. Using
      connectomic analyses based on graph theory, we computed global and local indices
      of functional connectivity (e.g., nodal strength, efficiency, clustering,
      betweenness centrality) and related these metrics to the five-factor-model (FFM)
      personality traits (i.e., neuroticism, extraversion, openness, agreeableness, and
      conscientiousness). The maximal information coefficient was used to assess for
      linear and non-linear statistical dependencies across the graph 'nodes', which
      were defined as distinct brain circuits identified via independent component
      analysis. Multi-variate regression models and 'train/test' machine-learning
      approaches were also used to examine the associations between FFM traits and
      connectomic indices as well as to test for the generalizability of the main
      findings, whilst accounting for age and sex differences. Conscientiousness was
      the sole FFM trait linked to measures of higher functional connectivity in the
      fronto-parietal and default mode networks. This might provide a mechanistic
      explanation of the behavioural observation that conscientious people are reliable
      and efficient in goal-setting or planning. Our study provides new inputs to
      understanding the neurological basis of personality and contributes to the
      development of more realistic models of the brain dynamics that mediate
      personality differences.

PMID- 30294716
TI  - DNA damaging agent-based antibody-drug conjugates for cancer therapy.
AB  - Currently, four antibody-drug conjugates (ADCs) are approved by the Food and Drug
      Administration or the European Medicine Agency to treat cancer patients. More
      than 60 ADCs are in clinical development for cancer therapy. More than 60% of
      ADCs in clinical trials employ microtubule inhibitors as their payloads. A better
      understanding of payloads other than microtubule inhibitors, especially DNA
      damaging agents, is important for further development of ADCs. In this review, we
      highlight an emerging trend of using DNA-damaging agents as payloads for ADCs.
      This review summarizes recent advances in our understanding gained from ongoing
      clinical studies; it will help to define the utility of DNA-damaging payloads for
      ADCs as cancer therapeutics. Future directions of the development of ADCs are
      also discussed, focusing on targeting drug resistance and combination treatment
      with immunotherapy.

PMID- 30294717
TI  - Synthetic Peptide CK2.3 Enhances Bone Mineral Density in Senile Mice.
AB  - Background: Osteoporosis is a silent disease caused by low bone mineral density
      that results in bone fractures in 1 out of 2 women and 1 in 4 men over the age of
      50. Although several treatments for osteopenia and osteoporosis are available,
      they have severe side effects and new treatments are desperately needed. Current
      treatments usually target osteoclasts and inhibit their activity or
      differentiation. Treatments that decrease osteoclast differentiation and activity
      but enhance osteogenesis and osteoblast activity are not available. We recently
      developed a peptide, CK2.3, that induces bone formation and increases bone
      mineral density as demonstrated by injection over the calvaria of 6 to 9-day-old
      mice and tail vein injection of 8-week-old mice. CK2.3 also decreased osteoclast
      formation and activity. However, these studies raise questions: does CK2.3 induce
      similar results in old mice and if so, what is the effective CK2.3 concentration
      and, is the bone mineral density of vertebrae of the spinal column increased as
      well? Methods: CK2.3 was systematically injected into the tail vein of female 6
      month old mice with various concentrations of CK2.3: 0.76 MUg/kg, 2.3 MUg/kg, or
      6.9 MUg/kg per mice. Mice were sacrificed one week, two weeks, and four weeks
      after the first injection. Their spines and femurs were collected and analyzed
      for bone formation. Results: Femur and lumbar spine analyses found increased bone
      mineral density (BMD) and mineral apposition rate, with greater stiffness
      observed in femoral samples four weeks after the first injection. Histochemistry
      showed that osteoclastogenesis was suppressed in CK2.3 treated senile mice.
      Conclusions: For the first time, this study showed the increase of lumbar spine
      BMD by CK2.3. Moreover, it showed that enhancement of femur BMD was accompanied
      by increased femur stiffness only at medium concentration of CK2.3 four weeks
      after the first injection indicating the maintenance of bone's structural
      integrity by CK2.3.

PMID- 30294718
TI  - Seed-Layer Free Zinc Tin Oxide Tailored Nanostructures for Nanoelectronic
      Applications: Effect of Chemical Parameters.
AB  - Semiconductor nanowires are mostly processed by complex, expensive, and high
      temperature methods. In this work, with the intent of developing zinc tin oxide
      nanowires (ZTO NWs) by low-cost and low-complexity processes, we show a detailed
      study on the influence of chemical parameters in the hydrothermal synthesis of
      ZTO nanostructures at temperatures of only 200  degrees C. Two different zinc
      precursors, the ratio between zinc and tin precursors, and the concentration of
      the surfactant agent and of the mineralizer were studied. The type and the
      crystallinity of the nanostructures were found to be highly dependent on the used
      precursors and on the concentration of each reagent. Conditions for obtaining
      different ZTO nanostructures were achieved, namely, Zn2SnO4 nanoparticles and
      ZnSnO3 nanowires with length ~600 nm, with the latter being reported for the
      first time ever by hydrothermal methods without the use of seed layers. Optical
      and electrical properties were analyzed, obtaining band gaps of 3.60 and 3.46 eV
      for ZnSnO3 and Zn2SnO4, respectively, and a resistivity of 1.42 kOmega.cm for
      single ZnSnO3 nanowires, measured using nanomanipulators after localized
      deposition of Pt electrodes by e-beam assisted gas decomposition. The low
      temperature hydrothermal methods explored here proved to be a low-cost,
      reproducible, and highly flexible route to obtain multicomponent oxide
      nanostructures, particularly ZTO NWs. The diversity of the synthesized ZTO
      structures has potential application in next-generation nanoscale devices such as
      field effect nanotransistors, nanogenerators, resistive switching memories, gas
      sensors, and photocatalysis.

PMID- 30294720
TI  - Evaluating Effectiveness of Mass and Continuous Long-lasting Insecticidal Net
      Distributions Over Time in Madagascar: A Sentinel Surveillance Based
      Epidemiological Study.
AB  - Background: The reduction of global malaria burden over the past 15 years is much
      attributed to the expansion of mass distribution campaigns (MDCs) of long-lasting
      insecticidal nets (LLIN). In Madagascar, two LUN MDCs were implemented and one
      district also benefited from a community-based continuous distribution (CB-CD).
      Malaria incidence dropped but eventually rebounded after a decade. Methods: Data
      from a sentinel surveillance network over the 2009-2015 period was analyzed.
      Alerts were defined as w eekly number o f malaria cases exceeding the 90th
      percentile value for three consecutive weeks. Statistical analyses assessed the
      temporal relationship between LLIN MDCs and (i) number of malaria cases and (ii)
      malaria alerts detected, and (iii) the effect of a combination of MDCs and a CB
      CD in Toamasina District. Findings: Analyses showed an increase of 13.6 points
      and 21.4 points in the percentile value of weekly malaria cases during the second
      and the third year following the MDC of LLINs respectively. The percentage of
      alert-free sentinel sites was 98.2% during the first year after LLIN MDC, 56.7%
      during the second year and 31.5% during the third year. The number of weekly
      malaria cases decreased by 14% during the CB-CD in Toamasina District. In
      contrast, sites without continuous distribution had a 12% increase of malaria
      cases. Interpretation: These findings support the malaria-preventive
      effectiveness of MDCs in Madagascar but highlight their limited duration when not
      followed by continuous distribution. The resulting policy implications are
      crucial to sustain reductions in malaria burden in high transmission settings.

PMID- 30294721
TI  - Automatic Archiving versus Default Deletion: What Snapchat Tells Us About
      Ephemerality in Design.
AB  - Unlike most social media, where automatic archiving of data is the default,
      Snapchat defaults to ephemerality: deleting content shortly after it is viewed by
      a receiver. Interviews with 25 Snapchat users show that ephemerality plays a key
      role in shaping their practices. Along with friend-adding features that
      facilitate a network of mostly close relations, default deletion affords
      everyday, mundane talk and reduces self-consciousness while encouraging playful
      interaction. Further, although receivers can save content through screenshots,
      senders are notified; this selective saving with notification supports complex
      information norms that preserve the feel of ephemeral communication while
      supporting the capture of meaningful content. This dance of giving and taking,
      sharing and showing, and agency for both senders and receivers provides the basis
      for a rich design space of mechanisms, levels, and domains for ephemerality.

PMID- 30294719
TI  - Sex Differences in Genetic Associations With Longevity.
AB  - IMPORTANCE: Sex differences in genetic associations with human longevity remain
      largely unknown; investigations on this topic are important for individualized
      health care. OBJECTIVE: To explore sex differences in genetic associations with
      longevity. DESIGN SETTING AND PARTICIPANTS: This population-based case-control
      study used sex-specific genome-wide association study and polygenic risk score
      (PRS) analyses to examine sex differences in genetic associations with longevity.
      Five hundred sixty-four male and 1614 female participants older than 100 years
      were compared with a control group of 773 male and 1526 female individuals aged
      40 to 64 years. All were Chinese Longitudinal Healthy Longevity Study
      participants with Han ethnicity who were recruited in 1998 and 2008 to 2014. MAIN
      OUTCOMES AND MEASURES: Sex-specific loci and pathways associated with longevity
      and PRS measures of joint effects of sex-specific loci. RESULTS: Eleven male
      specific and 11 female-specific longevity loci (P < 10-5) and 35 male-specific
      and 25 female-specific longevity loci (10-5 <= P < 10-4) were identified. Each of
      these loci's associations with longevity were replicated in north and south
      regions of China in one sex but were not significant in the other sex (P = .13
      .97), and loci-sex interaction effects were significant (P < .05). The
      associations of loci rs60210535 of the LINC00871 gene with longevity were
      replicated in Chinese women (P = 9.0 * 10-5) and US women (P = 4.6 * 10-5) but
      not significant in Chinese and US men. The associations of the loci rs2622624 of
      the ABCG2 gene were replicated in Chinese women (P = 6.8 * 10-5) and European
      women (P = .003) but not significant in both Chinese and European men. Eleven
      male-specific pathways (inflammation and immunity genes) and 34 female-specific
      pathways (tryptophan metabolism and PGC-1alpha induced) were significantly
      associated with longevity (P < .005; false discovery rate < 0.05). The PRS
      analyses demonstrated that sex-specific associations with longevity of the 4
      exclusive groups of 11 male-specific and 11 female-specific loci (P < 10-5) and
      35 male-specific and 25 female-specific loci (10-5 <=P < 10-4) were jointly
      replicated across north and south discovery and target samples. Analyses using
      the combined data set of north and south showed that these 4 groups of sex
      specific loci were jointly and significantly associated with longevity in one sex
      (P = 2.9 * 10-70 to 1.3 * 10-39) but not jointly significant in the other sex (P
      = .11 to .70), while interaction effects between PRS and sex were significant (P
      = 4.8 * 10-50 to 1.2 * 10-16). CONCLUSION AND RELEVANCE: The sex differences in
      genetic associations with longevity are remarkable, but have been overlooked by
      previously published genome-wide association studies on longevity. This study
      contributes to filling this research gap and provides a scientific basis for
      further investigating effects of sex-specific genetic variants and their
      interactions with environment on healthy aging, which may substantially
      contribute to more effective and targeted individualized health care for male and
      female elderly individuals.

PMID- 30294723
TI  - Prevalence and factors associated with self-reported chronic obstructive
      pulmonary disease among adults aged 40-79: the National Health and Nutrition
      Examination Survey (NHANES) 2007-2012.
AB  - Introduction: Chronic obstructive pulmonary disease (COPD) is a respiratory
      disease that often goes undiagnosed, particularly in its early stages. Objective:
      To examine sociodemographic, general health, and COPD specific factors, including
      severity of lung obstruction, that are associated with healthcare provider
      diagnosed COPD among U.S. adults. Methods: NHANES cross-sectional data collected
      from 2007-2012 on adults aged 40-79 years (n=10,219) were analyzed. The primary
      outcome was self-reported COPD diagnosis with predictive factors analyzed via chi
      square and logistic regression analyses. Results: During 2007-2012, 5.2% of US
      adults aged 40-79 reported being diagnosed with COPD. Among those diagnosed,
      50.8% reported fair or poor health, 47.1% were currently smoking cigarettes,
      49.1% were taking prescription respiratory medication, 36.4% had moderate or
      worse lung obstruction, and nearly 90% had one or more respiratory symptoms.
      Logistic regression revealed positive associations between receiving a COPD
      diagnosis and the following: being white (AOR: 3.08, 95% CI: 1.82-5.20); being
      aged 60-79 years (AOR: 1.65, 95% CI: 1.07-2.53); reporting fair/poor health (AOR:
      2.91, CI: 1.55-5.46); having 4-9 (AOR: 3.5, CI: 1.3-9.4) or 10 or more healthcare
      visits in prior year (AOR: 5.06, CI: 1.62-15.77); being a former (AOR: 1.75, CI:
      1.2-2.5) or current smoker (AOR: 1.70, CI: 1.17-2.48); having more severe lung
      obstruction (AOR: 4.90, CI: 3.28-7.32); having 3 or more respiratory symptoms
      (AOR: 22.07, CI: 12.03-40.49). Conclusions: Multiple factors are associated with
      self-reported COPD diagnosis with number of reported respiratory symptoms having
      the strongest association. After controlling for other factors, having mild lung
      obstruction was not associated with being diagnosed.

PMID- 30294724
TI  - Transcriptome-Guided Imaging Genetic Analysis via a Novel Sparse CCA Algorithm.
AB  - Imaging genetics is an emerging field that studies the influence of genetic
      variation on brain structure and function. The major task is to examine the
      association between genetic markers such as single nucleotide polymorphisms
      (SNPs) and quantitative traits (QTs) extracted from neuroimaging data. Sparse
      canonical correlation analysis (SCCA) is a bi-multivariate technique used in
      imaging genetics to identify complex multi-SNP-multi-QT associations. In imaging
      genetics, genes associated with a phenotype should at least expressed in the
      phenotypical region. We study the association between the genotype and amyloid
      imaging data and propose a transcriptome-guided SCCA framework that incorporates
      the gene expression information into the SCCA criterion. An alternating
      optimization method is used to solve the formulated problem. Although the problem
      is not biconcave, a closed-form solution has been found for each subproblem. The
      results on real data show that using the gene expression data to guide the
      feature selection facilities the detection of genetic markers that are not only
      associated with the identified QTs, but also highly expressed there.

PMID- 30294725
TI  - Non-invasive pulmonary function test on Morquio patients.
AB  - Morquio patients, in many cases, present with severe tracheal narrowing and
      restrictive lung problems making them susceptible to high mortality arising from
      sleep apnea and related complications. Tracheal obstruction with growth
      imbalance, short neck, adeno and tonsillar hypertrophy, large mandible, and/or
      pectus carinatum also contributes to the challenges in managing the airway with
      intubation and extubation due to factors intrinsic to Morquio syndrome. Taken
      together, these issues lead to serious respiratory distress and life-threatening
      complications during anesthetic procedures. Furthermore, patients with Morquio
      syndrome frequently cannot perform standard pulmonary function tests as a result
      of their distinctive skeletal dysplasia and chest deformity, thus making
      diagnosis of incipient pulmonary disease difficult. In many cases, conventional
      spirometry is too difficult for patients to complete, deriving from issues with
      cooperation or clinical circumstance. Therefore, it is an unmet challenge to
      assess pulmonary insufficiency with standard pulmonary function test (PFT) with
      minimal effort. Non-invasive PFT such as respiratory inductance plethysmography,
      impulse oscillometry system, and pneumotachography were described in Morquio
      patients as compared with spirometry. Findings from our previous study indicate
      that these non-invasive tests are a reliable approach to evaluate lung function
      in a larger range of patients, and provide valuable clinical information
      otherwise unobtainable from invasive tests. In conclusion, the present study
      describes the utility of non-invasive (PFT) to accommodate a broad range of
      patients including intolerance to effort-dependent PFT.

PMID- 30294726
TI  - Tumor-aware, Adversarial Domain Adaptation from CT to MRI for Lung Cancer
      Segmentation.
AB  - We present an adversarial domain adaptation based deep learning approach for
      automatic tumor segmentation from T2-weighted MRI. Our approach is composed of
      two steps: (i) a tumor-aware unsupervised cross-domain adaptation (CT to MRI),
      followed by (ii) semi-supervised tumor segmentation using Unet trained with
      synthesized and limited number of original MRIs. We introduced a novel target
      specific loss, called tumor-aware loss, for unsupervised cross-domain adaptation
      that helps to preserve tumors on synthesized MRIs produced from CT images. In
      comparison, state-of-the art adversarial networks trained without our tumor-aware
      loss produced MRIs with ill-preserved or missing tumors. All networks were
      trained using labeled CT images from 377 patients with non-small cell lung cancer
      obtained from the Cancer Imaging Archive and unlabeled T2w MRIs from a completely
      unrelated cohort of 6 patients with pre-treatment and 36 on-treatment scans.
      Next, we combined 6 labeled pre-treatment MRI scans with the synthesized MRIs to
      boost tumor segmentation accuracy through semi-supervised learning. Semi
      supervised training of cycle-GAN produced a segmentation accuracy of 0.66
      computed using Dice Score Coefficient (DSC). Our method trained with only
      synthesized MRIs produced an accuracy of 0.74 while the same method trained in
      semi-supervised setting produced the best accuracy of 0.80 on test. Our results
      show that tumor-aware adversarial domain adaptation helps to achieve reasonably
      accurate cancer segmentation from limited MRI data by leveraging large CT
      datasets.

PMID- 30294727
TI  - Image Super-Resolution by Supervised Adaption of Patchwise Self-similarity from
      High-Resolution Image.
AB  - Image super-resolution is of great interest in medical imaging field. However,
      different from natural images studied in computer vision field, the low
      resolution (LR) medical imaging data is often a stack of high-resolution (HR) 2D
      slices with large slice thickness. Consequently, the goal of super-resolution for
      medical imaging data is to reconstruct the missing slice(s) between any two
      consecutive slices. Since some modalities (e.g., T1-weighted MR image) are often
      acquired with high-resolution (HR) image, it is intuitive to harness the prior
      self-similarity information in the HR image for guiding the super-resolution of
      LR image (e.g., T2-weighted MR image). The conventional way is to find the
      profile of patchwise self-similarity in the HR image and then use it to
      reconstruct the missing information at the same location of LR image. However,
      the local morphological patterns could vary significantly across the LR and HR
      images, due to the use of different imaging protocols. Therefore, such direct (un
      supervised) adaption of self-similarity profile from HR image is often not
      effective in revealing the actual information in the LR image. To this end, we
      propose to employ the existing image information in the LR image to supervise the
      estimation of self-similarity profile by requiring it not only being optimal in
      representing patches in the HR image, but also producing less reconstruction
      errors for the existing image information in the LR image. Moreover, to make the
      anatomical structures spatially consistent in the reconstructed image, we
      simultaneously estimate the self-similarity profiles for a stack of patches
      across consecutive slices by solving a group sparse patch representation problem.
      We have evaluated our proposed super-resolution method on both simulated brain MR
      images and real patient images with multiple sclerosis lesion, achieving
      promising results with more anatomical details and sharpness.

PMID- 30294722
TI  - Regulation of Immune Cell Migration by Sphingosine-1-Phosphate.
AB  - Sphingosine-1-phosphate [S1P] is a potent bioactive sphingolipid molecule. In
      response to a stimulus, S1P is produced intracellularly by the action of two
      sphingosine kinases, and then it is exported to the extracellular environment or
      acts as an intracellular second messenger. S1P binds to its cognate G-protein
      coupled receptors, which are known as S1P receptors. There are five S1P receptors
      that have been identified in vertebrates. By activating S1P receptors, S1P
      controls a variety of physiological and pathological processes including cell
      migration, angiogenesis, vascular maturation, inflammation, and invasion,
      metastasis, and chemoresistance in cancer. S1P has emerged as a critical
      regulator of leukocyte migration and plays a central role in lymphocyte egress
      from the thymus and secondary lymphoid organs. In the current review article, we
      summarize the current understanding of the emigration of lymphocytes and other
      leukocytes from bone marrow, thymus and secondary lymphoid organs to the
      circulation, as well as the clinical implications of modulating the activity of
      the major S1P receptor, S1PR1.

PMID- 30294728
TI  - Consistent Multi-Atlas Hippocampus Segmentation for Longitudinal MR Brain Images
      with Temporal Sparse Representation.
AB  - In this paper, we propose a novel multi-atlas based longitudinal label fusion
      method with temporal sparse representation technique to segment hippocampi at all
      time points simultaneously. First, we use groupwise longitudinal registration to
      simultaneously (1) estimate a group-mean image of a subject image sequence and
      (2) register its all time-point images to the estimated group-mean image
      consistently over time. Then, by registering all atlases with the group-mean
      image, we can align all atlases longitudinally consistently to each time point of
      the subject image sequence. Finally, we propose a longitudinal label fusion
      method to propagate all atlas labels to the subject image sequence by
      simultaneously labeling a set of temporally-corresponded voxels with a temporal
      consistency constraint on sparse representation. Experimental results demonstrate
      that our proposed method can achieve more accurate and consistent hippocampus
      segmentation than the state-of-the-art counterpart methods.

PMID- 30294729
TI  - Mindless Computing: Designing Technologies to Subtly Influence Behavior.
AB  - Persuasive technologies aim to influence user's behaviors. In order to be
      effective, many of the persuasive technologies de-veloped so far relies on user's
      motivation and ability, which is highly variable and often the reason behind the
      failure of such technology. In this paper, we present the concept of Mindless
      Computing, which is a new approach to persuasive technology design. Mindless
      Computing leverages theories and concepts from psychology and behavioral
      economics into the design of technologies for behavior change. We show through a
      systematic review that most of the current persuasive technologies do not utilize
      the fast and automatic mental processes for behavioral change and there is an
      opportunity for persuasive technology designers to develop systems that are less
      reliant on user's motivation and ability. We describe two examples of mindless
      technologies and present pilot studies with encouraging results. Finally, we
      discuss design guidelines and considerations for developing this type of
      persuasive technology.

PMID- 30294730
TI  - Cannabis and Myocardial Infarction: Risk Factors and Pathogenetic Insights.
AB  - Cannabis use in the US is rising with increased legalization. It has been noted
      that there is a five-fold increase risk of Myocardial Infarctions (MI) in the
      first hour after cannabis use. Traditional risk factors for MI include diabetes,
      hypertension and dyslipidemia. The rising use of cannabis may have ushered in an
      additional MI risk factor to be added to the list; that is cannabis. In this
      review, we discuss the growing use of cannabis and potential link with MI,
      highlighting the common pathogenic hypotheses linking these risk factors.

PMID- 30294731
TI  - FOXF2 differentially regulates expression of metabolic genes in non-cancerous and
      cancerous breast epithelial cells.
AB  - Forkhead box F2 (FOXF2) functions as a transcription factor and is critically
      involved in programming organogenesis and regulating epithelial-to-mesenchymal
      transition (EMT) and cell proliferation. We recently have revealed that FOXF2 can
      exert distinct functional effects on different molecular subtypes of breast
      cancer. We found that FOXF2 expression is epigenetically silenced in luminal
      breast cancers due to its tumor-suppressive role in DNA replication regulation.
      In contrast, FOXF2 is overexpressed in basal-like triple-negative breast cancers
      (TNBCs) due to its oncogenic role in promoting EMT. Although our and other
      studies have shown that FOXF2 dysregulation is critical for tumorigenesis of
      various tissue types, the role of FOXF2 in metabolic rewiring of cancer remains
      unknown. In this study, we analyzed our previous microarray data to understand
      the metabolic role of FOXF2 in non-cancerous and cancerous breast epithelial
      cells. Our studies showed that in non-cancerous breast epithelial cells FOXF2 can
      also play a dual role either in tumor suppression or in tumor promotion through
      regulating expression of tumor-suppressive and oncogenic metabolic genes.
      Furthermore, we found that FOXF2-regulated metabolic genes are not conserved
      between non-cancerous and cancerous breast epithelial cells and FOXF2 is involved
      in metabolic rewiring in breast cancer cells. This is the first report to explore
      the metabolic function of FOXF2 in breast cancer.

PMID- 30294732
TI  - Constructing multi-interface Mo2C/Co@C nanorods for a microwave response based on
      a double attenuation mechanism.
AB  - In this work, novel one-dimensional (1D) Mo2C/Co@C nanorods (MCRs), using a metal
      organic framework (zeolitic imidazolate framework; ZIF-67) as the coating layer
      to form multi-interfaces, were formed via a facile hard template method. Compared
      with previous works relating to porous-carbon-based Mo2C nanocomposites, the well
      designed MCRs in this study possess a double attenuation mechanism due to the
      existence of the dielectric materials Mo2C and remaining carbon (RC) and the
      magnetic compound Co. Thanks to a new design and the multiple useful compounds,
      the as-prepared MCRs have the features of demonstrating multi-interfacial
      polarization, a large surface area and highly isotropic dissipation. Hence, the
      samples not only inherit the excellent microwave absorbing abilities of Mo2C but
      they also have a broadened effective bandwidth. For example, the minimum
      reflection loss (RL) value of MCRs with 35% sample loading could reach -47.98 dB.
      More importantly, RL values of less than -10 dB can be observed from 11.08 to
      17.08 GHz (an effective bandwidth of 6.0 GHz) with a matching thickness of 1.6
      mm, which is much better than previous work involving porous-carbon-based Mo2C
      nanocomposites. Firstly, we have reasonably redesigned the samples to have good
      absorbing properties for practical applications. Secondly, we have paved a highly
      efficient and universal way to synthesize 1D microwave absorbers with multiple
      valuable interfaces.

PMID- 30294733
TI  - Selective monoalkylation of p-tert-butylcalix-[4]-arene in a methyl carbonate
      ionic liquid.
AB  - Methyl carbonate ionic liquids are shown to readily mono-deprotonate p-tert
      butylcalix-[4]-arenes initiating the formation of an organic mono-anionic p-tert
      butylcalix-[4]-arate salt, methanol and carbon dioxide. These calix-[4]-arate
      salts have been successfully used in alkylation reactions with dialkyl sulfates
      and alkyl halides to form a mono-alkylated single product with high yield. This
      method avoids the common use of alkali metal bases such as caesium fluoride hence
      providing a safer and more selective synthetic route.

PMID- 30294737
TI  - A four-state fluorescent molecular switch.
AB  - Four distinct fluorescent states are achieved in a single Weak-Link Approach
      (WLA) construct bearing pyrene and tetraphenylethene moieties. The fluorescence
      of the compound in both the solution and solid phases can be manipulated through
      reversible coordination chemistry at the PtII center.

PMID- 30294739
TI  - Dual plasmonically tunable slow light based on plasmon-induced transparency in
      planar graphene ribbon metamaterials.
AB  - We propose a simulated terahertz design based on planar graphene ribbons. With
      numerical simulation, we can achieve a very obvious dual plasmon-induced
      transparency phenomenon through the destructive interference in this structure.
      Moreover, due to the simple design of this structure and the complete continuous
      graphene ribbons, the Fermi level of graphene can be regulated by voltage. Thus,
      the dual plasmon-induced transparency phenomenon can be easily tuned in the
      numerical simulation. Further structural analysis shows that the two graphene
      chips on the side of the graphene ribbons play a crucial role in the dual plasmon
      induced transparency phenomenon. As the length of the two chips is close, the
      dual plasmon-induced transparency phenomenon gradually becomes a single plasmon
      induced transparency phenomenon. The theoretical analysis of this structure shows
      that this system has a very high group index, and its maximum value is 800, which
      is far greater than that of other types of slow light devices. This work may open
      up a new way for designing tunable terahertz graphene-based devices and slow
      light devices.

PMID- 30294740
TI  - Low temperature reaction dynamics for CH3OH + OH collisions on a new full
      dimensional potential energy surface.
AB  - Is the rise of the rate constant measured in laval expansion experiments of OH
      with organic molecules at low temperatures due to the reaction between the
      reactants or due to the formation of complexes with the buffer gas? This question
      has importance for understanding the evolution of prebiotic molecules observed in
      different astrophysical objects. Among these molecules methanol is one of the
      most widely observed, and its reaction with OH has been studied by several groups
      showing a fast increase in the rate constant under 100 K. Transition state theory
      doesn't reproduce this behavior and here dynamical calculations are performed on
      a new full dimensional potential energy surface developed for this purpose. The
      calculated classical reactive cross sections show an increase at low collision
      energies due to a complex forming mechanism. However, the calculated rate
      constant at temperatures below 100 K remains lower than the observed one. Quantum
      effects are likely responsible for the measured behavior at low temperatures.

PMID- 30294741
TI  - Intermolecular pi-hole/n->pi* interactions with carbon monoxide ligands in
      crystal structures.
AB  - A thorough analysis of the Cambridge Structure Database reveals that
      intermolecular pi-hole/n->pi* interactions with carbon monoxide ligands are
      abundant in the solid state and somewhat directional, particularly with fac-like
      M(CO)3 fragments (P < 4.0). High level DFT calculations suggest interacting
      energies up to about -10 kcal mol-1 for adducts of charge neutral complexes.

PMID- 30294742
TI  - Square-planar Co(iii) in {O4} coordination: large ZFS and reactivity with ROS.
AB  - Oxidation of distorted square-planar perfluoropinacolate Co compound
      [CoII(pinF)2]2-, 1, to [CoIII(pinF)2]1-, 2, is reported. Rigidly square-planar 2
      has an intermediate-spin, S = 1, ground state and very large zero-field splitting
      (ZFS) with D = 67.2 cm-1; |E| = 18.0 cm-1, (E/D = 0.27), g? = 2.10, g|| = 2.25
      and chiTIP = 1950 * 10-6 cm3 mol-1. This Co(iii) species, 2, reacts with ROS to
      oxidise two (pinF)2- ligands to form tetrahedral [CoII(Hpfa)4]2-, 3.

PMID- 30294743
TI  - Significant effect of Mg-pressure-controlled annealing: non-stoichiometry and
      thermoelectric properties of Mg2-deltaSi1-xSbx.
AB  - Non-stoichiometry related to such an element with high vapor pressure as Mg has
      been difficult to control, despite its significant influence on the
      thermoelectric properties of the material. Here, Mg non-stoichiometry and the
      thermoelectric properties of Mg2-deltaSi1-xSbx (0 <= x <= 0.60) are investigated
      systematically by tuning the Mg partial pressure during annealing. The range of
      Mg non-stoichiometry Deltadelta depends on x since the Sb dopant induces Mg
      vacancies, which are partly filled by Mg atoms in the gas phase according to an
      equilibrium reaction. The defect association between the Mg vacancies and the Sb
      dopant decreases Deltadelta at high Sb contents. The maximum Deltadelta of 0.016,
      which corresponds to a carrier concentration range Deltan of 4.9 * 1020 cm-3, is
      obtained at x = 0.10. The Seebeck coefficient shows a universal relationship with
      the carrier concentration, which can be explained by the DFT-calculated band
      structure within the rigid band approximation. The carrier mobility is reduced
      significantly as a result of carrier scattering at the Mg-poor grain boundaries.
      The vacancy formation at the Mg-site, in addition to Si-site substitution for Sb,
      effectively suppresses the lattice thermal conductivity. The low thermal
      conductivity on the Mg-poor side increases the maximum zT, while a high energy
      conversion efficiency is obtained on the Mg-rich side, owing to the high
      electrical conductivity and resultant large zT at low temperatures. Mg non
      stoichiometry is a key factor in tuning the thermoelectric properties of Mg2Si
      based materials and thus its control is essential.

PMID- 30294744
TI  - Reactivity of the O2+.(H2O)n and NO+.(H2O)n cluster ions in the D-region of the
      ionosphere.
AB  - The protonated water clusters present in the D-region of the ionosphere have been
      postulated to be formed from cluster ions such as O2+.(H2O)n and NO+.(H2O)n,
      although the detailed mechanism of the underlying reactions is not understood.
      Second order Moller-Plesset perturbation theory based Born-Oppenheimer ab initio
      molecular dynamics (AIMD) simulations of the reactions of the O2+.(H2O)n and
      NO+.(H2O)n cluster ions to form protonated water clusters reveal different
      mechanisms for the O2+ and NO+ based ions. AIMD simulations of O2+.(H2O)n=2-5
      with initial velocities of the atoms sampled from the Maxwell-Boltzmann
      distribution at 220 K show that following charge transfer, a reaction to form a
      protonated water cluster and OH occurs rapidly where the neutral O2 molecule is
      just a spectator. In contrast, the reaction of NO+.(H2O)n=4,5 has been
      hypothesised to involve an intracluster reaction, but no reaction is observed in
      AIMD simulations using thermal initial velocities. However, it is shown that
      reactions to form protonated water clusters do occur in simulations when a water
      molecule collides with a NO+.(H2O)4 cluster.

PMID- 30294747
TI  - Dental Pulp Stem Cells in Customized 3D Nanofibrous Scaffolds for Regeneration of
      Peripheral Nervous System.
AB  - Dental pulp stem cells (DPSCs) are adult multipotent stem cells of
      neuroectodermal origin; they provide an encouraging perspective in the domain of
      nerve tissue engineering. DPSCs could be transplanted in biodegradable
      electrospun neuro-supportive scaffold (optimized in various 3D geometries like
      coating on the surface of titanium implant, hollow/solid tubes, etc.) for
      enhanced in vivo recovery of peripheral nerves. Herein, we describe the
      fabrication of uniform bead-free nanofibrous scaffold which supports DPSCs,
      proliferation, and their subsequent neural differentiation and thus could be
      utilized for enhanced regeneration of peripheral nervous system.

PMID- 30294746
TI  - Validation of gallbladder absorbed radiation dose reduction simulation: human
      dosimetry of [18F]fluortriopride.
AB  - BACKGROUND: [18F]Fluortriopride (FTP) was developed as a dopamine D3-selective
      radiotracer, thought to be important to neurobiological reward pathways and
      implicated in drug addiction, Parkinson's disease, and schizophrenia. Preclinical
      radiation dosimetry studies found the gallbladder wall received the highest dose.
      A gallbladder dose reduction intervention was simulated using a novel reduction
      model for healthy adults following fatty-meal consumption. The goals of this
      study were to assess whole body FTP human dosimetry and determine the feasibility
      of reducing absorbed dose to the gallbladder wall. RESULTS: Effective dose
      without a fatty meal was 0.022 +/- 0.002 mSv/MBq (+/- standard deviation) with
      highest organ dose of 0.436 +/- 0.178 mSv/MBq to the gallbladder wall (n = 10).
      Predicted gallbladder dose reduction with fatty meal consumed was 67.4% (n = 10).
      Meal consumption by four repeat volunteers decreased average gallbladder dose by
      71.3% (n = 4) compared to the original ten volunteers. CONCLUSIONS: Observed
      effective doses were adequately low to continue studying FTP uptake in humans.
      Validated dosimetry simulations indicate up to a 71% reduction in gallbladder
      dose can be achieved by employing intrinsic physiology to contract the
      gallbladder via fatty meal ingestion. This methodology for predicting gallbladder
      absorbed dose reduction from fatty meal consumption can be applied to other
      radiopharmaceuticals and radiotherapies.

PMID- 30294748
TI  - Sphagnum Species Modulate their Phenolic Profiles and Mycorrhizal Colonization of
      Surrounding Andromeda polifolia along Peatland Microhabitats.
AB  - Sphagnum mosses mediate long-term carbon accumulation in peatlands. Given their
      functional role as keystone species, it is important to consider their responses
      to ecological gradients and environmental changes through the production of
      phenolics. We compared the extent to which Sphagnum phenolic production was
      dependent on species, microhabitats and season, and how surrounding dwarf shrubs
      responded to Sphagnum phenolics. We evaluated the phenolic profiles of aqueous
      extracts of Sphagnum fallax and Sphagnum magellanicum over a 6-month period in
      two microhabitats (wet lawns versus dry hummocks) in a French peatland. Phenolic
      profiles of water-soluble extracts were measured by UHPLC-QTOF-MS. Andromeda
      polifolia mycorrhizal colonization was quantified by assessing the intensity of
      global root cortex colonization. Phenolic profiles of both Sphagnum mosses were
      species-, season- and microhabitat- dependant. Sphagnum-derived acids were the
      phenolics mostly recovered; relative quantities were 2.5-fold higher in S. fallax
      than in S. magellanicum. Microtopography and vascular plant cover strongly
      influenced phenolic profiles, especially for minor metabolites present in low
      abundance. Higher mycorrhizal colonization of A. polifolia was found in lawns as
      compared to hummocks. Mycorrhizal abundance, in contrast to environmental
      parameters, was correlated with production of minor phenolics in S. fallax. Our
      results highlight the close interaction between mycorrhizae such as those
      colonizing A. polifolia and the release of Sphagnum phenolic metabolites and
      suggest that Sphagnum-derived acids and minor phenolics play different roles in
      this interaction. This work provides new insight into the ecological role of
      Sphagnum phenolics by proposing a strong association with mycorrhizal
      colonization of shrubs.

PMID- 30294749
TI  - Not scene learning, but attentional processing is superior in team sport athletes
      and action video game players.
AB  - We tested if high-level athletes or action video game players have superior
      context learning skills. Incidental context learning was tested in a spatial
      contextual cueing paradigm. We found comparable contextual cueing of visual
      search in repeated displays in high-level amateur handball players, dedicated
      action video game players and normal controls. In contrast, both handball players
      and action video game players showed faster search than controls, measured as
      search time per display item, independent of display repetition. Thus, our data
      do not indicate superior context learning skills in athletes or action video game
      players. Rather, both groups showed more efficient visual search in abstract
      displays that were not related to sport-specific situations.

PMID- 30294750
TI  - Linear-nonlinear-time-warp-poisson models of neural activity.
AB  - Prominent models of spike trains assume only one source of variability -
      stochastic (Poisson) spiking - when stimuli and behavior are fixed. However,
      spike trains may also reflect variability due to internal processes such as
      planning. For example, we can plan a movement at one point in time and execute it
      at some arbitrary later time. Neurons involved in planning may thus share an
      underlying time course that is not precisely locked to the actual movement. Here
      we combine the standard Linear-Nonlinear-Poisson (LNP) model with Dynamic Time
      Warping (DTW) to account for shared temporal variability. When applied to
      recordings from macaque premotor cortex, we find that time warping considerably
      improves predictions of neural activity. We suggest that such temporal
      variability is a widespread phenomenon in the brain which should be modeled.

PMID- 30294752
TI  - Correction to: Regenerative therapies increase survivorship of avascular necrosis
      of the femoral head: a systematic review and meta-analysis.
AB  - There is an error in the original publication. Affiliation of corresponding
      author (Giulia Merli) was incorrectly published. Correct presentation is Nano
      Biotechnology Laboratory-NaBi IRCCS- Istituto Ortopedico, Rizzoli, Italy.

PMID- 30294753
TI  - Biodegradation of sulfamethoxazole by a bacterial consortium of Achromobacter
      denitrificans PR1 and Leucobacter sp. GP.
AB  - In the last decade, biological degradation and mineralization of antibiotics have
      been increasingly reported feats of environmental bacteria. The most extensively
      described example is that of sulfonamides that can be degraded by several members
      of Actinobacteria and Proteobacteria. Previously, we reported sulfamethoxazole
      (SMX) degradation and partial mineralization by Achromobacter denitrificans
      strain PR1, isolated from activated sludge. However, further studies revealed an
      apparent instability of this metabolic trait in this strain. Here, we
      investigated this instability and describe the finding of a low-abundance and
      slow-growing actinobacterium, thriving only in co-culture with strain PR1. This
      organism, named GP, shared highest 16S rRNA gene sequence similarity (94.6-96.9%)
      with the type strains of validly described species of the genus Leucobacter. This
      microbial consortium was found to harbor a homolog to the sulfonamide
      monooxygenase gene (sadA) also found in other sulfonamide-degrading bacteria.
      This gene is overexpressed in the presence of the antibiotic, and evidence
      suggests that it codes for a group D flavin monooxygenase responsible for the
      ipso-hydroxylation of SMX. Additional side reactions were also detected
      comprising an NIH shift and a Baeyer-Villiger rearrangement, which indicate an
      inefficient biological transformation of these antibiotics in the environment.
      This work contributes to further our knowledge in the degradation of this
      ubiquitous micropollutant by environmental bacteria.

PMID- 30294754
TI  - Recent advances in experimental polyphosphazene adjuvants and their mechanisms of
      action.
AB  - Vaccination continues to be a very important public health intervention to
      control infectious diseases in the world. Subunit vaccines are generally poorly
      immunogenic and require the addition of adjuvants to induce protective immune
      responses. Despite their critical role in vaccines, adjuvant mechanism of action
      remains poorly understood, which is a barrier to the development of new, safe and
      effective vaccines. In the present review, we focus on recent progress in
      understanding the mechanisms of action of the experimental adjuvants
      poly[di(carboxylatophenoxy)phosphazene] (PCPP) and poly[di(sodiumcarboxylatoethyl
      phenoxy)phosphazene] (PCEP) (in this review, adjuvants PCPP and PCEP are
      collectively referred to as PZ denoting polyphosphazenes). PZs are high molecular
      weight, water-soluble, synthetic polymers that have been shown to regulate innate
      immune response genes, induce cytokines and chemokines secretion at the site of
      injection and, also, induce immune cell recruitment to the site of injection to
      create a local immune-competent environment. There is an evidence that as well as
      its role as an immunoadjuvant (that activate innate immune responses), PZ can
      also act as a vaccine carrier. The mechanism of action that explains how PZ leads
      to these effects is not known and is a barrier to the development of designer
      vaccines.

PMID- 30294756
TI  - Identifying core components and indicators of successful transitions from child
      to adult mental health services: a scoping review.
AB  - The aim of this scoping review was to identify the core components of
      interventions that facilitate successful transition from child and adolescent
      mental health services to adult mental health services. In the absence of
      rigorous evaluations of transition program effectiveness for transitioning youth
      with mental health care needs, these core components can contribute to informed
      decisions about promising program and intervention strategies. This review
      examined data from 87 peer-reviewed and non-academic documents to determine the
      characteristics that support the transition process and to identify opportunities
      for system and program improvement. Data were extracted and synthesized using a
      descriptive analytic framework. A major finding of this review is a significant
      lack of measurable indicators in the academic and gray literature. This review
      did identify 26 core components organized within the framework of the six core
      elements of healthcare transitions. Policy makers, practitioners, and
      administrators can use the core components to guide decisions about transition
      program and intervention content. Confirmation of the impact of these core
      program components on youth outcomes awaits the conduct of rigorous randomized
      trials. Future research also needs to explicitly focus on the development of
      indicators to evaluate transition programs and interventions.

PMID- 30294757
TI  - Development of an in silico prediction model for chemical-induced urinary tract
      toxicity by using naive Bayes classifier.
AB  - The urinary tract toxicity is one of the major reasons for investigational drugs
      not coming into the market and even marketed drugs being restricted or withdrawn.
      The objective of this investigation is to develop an easily interpretable and
      practically applicable in silico prediction model of chemical-induced urinary
      tract toxicity by using naive Bayes classifier. The genetic algorithm was used to
      select important molecular descriptors related to urinary tract toxicity, and the
      ECFP-6 fingerprint descriptors were applied to the urinary tract toxic/non-toxic
      fragments production. The established naive Bayes classifier (NB-2) produced
      87.3% overall accuracy of fivefold cross-validation for the training set and
      84.2% for the external test set, which can be employed for the chemical-induced
      urinary tract toxicity assessment. Furthermore, six important molecular
      descriptors (e.g., number of N atoms, AlogP, molecular weight, number of H
      acceptors, number of H donors and molecular fractional polar surface area) and
      toxic and non-toxic fragments were obtained, which would help medicinal chemists
      interpret the mechanisms of urinary tract toxicity, and even provide theoretical
      guidance for hit and lead optimization.

PMID- 30294755
TI  - Combination systemic therapies with immune checkpoint inhibitors in pancreatic
      cancer: overcoming resistance to single-agent checkpoint blockade.
AB  - Immune checkpoint inhibitors have demonstrated broad single-agent antitumor
      activity and a favorable safety profile that render them attractive agents to
      combine with other systemic anticancer therapies. Pancreatic cancer has been
      fairly resistant to monotherapy blockade of programmed cell death protein 1
      receptor, programmed death ligand 1, and cytotoxic T-lymphocyte associated
      protein 4. However, there is a growing body of preclinical evidence to support
      the rational combination of checkpoint inhibitors and various systemic therapies
      in pancreatic cancer. Furthermore, early clinical evidence has begun to support
      the feasibility and efficacy of checkpoint inhibitor-based combination therapy in
      advanced pancreatic cancer. Despite accumulating preclinical and clinical data,
      there remains several questions as to the optimal dosing and timing of
      administration of respective agents, toxicity of combination strategies, and
      mechanisms by which immune resistance to single-agent checkpoint blockade are
      overcome. Further development of biomarkers is also important in the advancement
      of combination systemic therapies incorporating checkpoint blockade in pancreatic
      cancer. Results from an impressive number of ongoing prospective clinical trials
      are eagerly anticipated and will seek to validate the viability of combination
      immuno-oncology strategies in pancreatic cancer.

PMID- 30294758
TI  - Parental Health Spillover in Cost-Effectiveness Analysis: Evidence from Self
      Harming Adolescents in England.
AB  - OBJECTIVE: This article presents alternative parental health spillover
      quantification methods in the context of a randomised controlled trial comparing
      family therapy with treatment as usual as an intervention for self-harming
      adolescents, and discusses the practical limitations of those methods. METHODS:
      The trial followed a sample of 754 participants aged 11-17 years. Health
      utilities are measured using answers to the EuroQoL 5 Dimensions 3 Levels (EQ-5D
      3L) for the adolescent and the Health Utility Index (HUI2) for one parent at
      baseline, 6 and 12 months. We use regression analyses to evaluate the association
      between the parent's and adolescent's health utilities as part of an explanatory
      regression model including health-related and demographic characteristics of both
      the adolescent and the parent. We then measure cost-effectiveness over a 12-month
      period as mean incremental cost-effectiveness ratios using various spillover
      quantification methods. We propose an original quantification based on the use of
      a household welfare function along with an equivalence scale to generate a health
      gain within the family to be added to the adolescent's quality-adjusted life-year
      gain. RESULTS: We find that the parent's health utility increased over the
      duration of the trial and is significantly and positively associated with
      adolescent's health utility at 6 and 12 months but not at baseline. When
      considering the adolescent's health gain only, the incremental cost-effectiveness
      ratio is L40,453 per quality-adjusted life-year. When including the health
      spillover to one parent, the incremental cost-effectiveness ratio estimates range
      from L27,167 per quality-adjusted life-year to L40,838 per quality-adjusted life
      year and can be a dominated option depending on the quantification method used.
      CONCLUSION: According to the health spillover quantification method considered,
      the incremental cost-effectiveness ratios vary from within the National Institute
      for Health and Care Excellence (NICE) cost-effectiveness threshold range to not
      being cost-effective.

PMID- 30294759
TI  - Gut microbiota and Hashimoto's thyroiditis.
AB  - About two third of the human microbial commensal community, namely the gut
      microbiota, is hosted by the gastrointestinal tract which represents the largest
      interface of the organism to the external environment. This microbial community
      co-evolved in a symbiotic relationship with the human beings. Growing evidence
      support the notion that the microbiota plays a significant role in maintaining
      nutritional, metabolic and immunologic homeostasis in the host. Microbiota,
      beside the expected role in maintaining gastrointestinal homeostasis also exerts
      metabolic functions in nutrients digestion and absorption, detoxification and
      vitamins' synthesis. Intestinal microbiota is also key in the correct development
      of the lymphoid system, 70% of which resides at the intestinal level. Available
      studies, both in murine models and humans, have shown an altered ratio between
      the different phyla, which characterize a" normal" gut microbiota, in a number of
      different disorders including obesity, to which a significant part of the studies
      on intestinal microbiota has been addressed so far. These variations in gut
      microbiota composition, known as dysbiosis, has been also described in patients
      bearing intestinal autoimmune diseases as well as type 1 diabetes mellitus,
      systemic sclerosis and systemic lupus erythematosus. Being Hashimoto's
      thyroiditis the most frequent autoimmune disorder worldwide, the analysis of the
      reciprocal influence with intestinal microbiota gained interest. The whole
      thyroid peripheral homeostasis may be sensitive to microbiota changes but there
      is also evidence that the genesis and progression of autoimmune thyroid disorders
      may be significantly affected from a changing intestinal microbial composition or
      even from overt dysbiosis. In this brief review, we focused on the main features
      which characterize the reciprocal influence between microbiota and thyroid
      autoimmunity described in the most recent literature.

PMID- 30294760
TI  - Diagnosis of diastolic dysfunction in the emergency department: really at reach
      for minimally trained sonologists? A call for a wise approach to heart failure
      with preserved ejection fraction diagnosis in the ER.

PMID- 30294761
TI  - Hopelessness and Delinquent Behavior as Predictors of Community Violence Exposure
      in Ethnic Minority Male Adolescent Offenders.
AB  - Justice-involved boys from urban communities are disproportionately impacted by
      community violence exposure (ECV) and despite decades of research, rates of ECV
      in youth continue to increase particularly for youth involved in the juvenile
      justice system. Despite the increased risk of exposure, the majority of research
      focuses on what may protect youth from the deleterious outcomes associated with
      violence exposure, rather than strategies that may prevent the violence exposure
      from occurring. The current study seeks to shift the focus of research in this
      area to examining factors that may predict future violence exposure.
      Specifically, the purpose of the current study is to examine the role of
      hopelessness as a predictor of the risk for violence exposure in a sample of 831
      justice-involved, urban boys ages 14-18 (52.2% African American, 42.1% Hispanic,
      5.7% other). Results revealed that baseline levels of low aspirations and
      hopelessness towards the future indirectly predicted violence exposure 1 year
      later through engagement in delinquent behavior. Clinical implications for
      targeting youth with elevated risk and preventing future violence exposure are
      discussed.

PMID- 30294762
TI  - Novel mixed hemimicelles based on nonionic surfactant-imidazolium ionic liquid
      and magnetic halloysite nanotubes as efficient approach for analytical
      determination.
AB  - The co-adsorption of mixed nonionic surfactant and imidazolium-based ionic
      liquid, Triton X100 (TX100), with 1-cetyl-3-methylimidazolium bromide (C16mimBr)
      adsorbed onto the surface of magnetic halloysite nanotubes (MHNTs) was used as an
      efficient adsorbent for simultaneous determination of amlodipine and nimodipine
      in urine. The designed adsorbent was characterized by TEM, TGA, FTIR, and DLS
      analysis methods. All the parameters that influence the extraction efficiency are
      optimized with the aid of response surface methodology (RSM). The effects of
      nonionic surfactant TX100 with different structures of ionic-liquid-coated MHNTs
      were investigated. Under optimum conditions, extraction recoveries of amlodipine
      and nimodipine were in the range of 73.8-81.2 and 94.3-96.1%, with RSDs (n = 3)
      of 2.6-5.5% in spiked urine samples, respectively. The adsorption mechanism
      principal of mixed hemimicelles was discussed in this study. The limit of
      detection obtained for analytes was < 0.002 MUg.mL-1. To our knowledge, this was
      the first attempt using a mixed hemimicelle solid-phase extraction (SPE) based on
      MHNTs and nonionic surfactant and imidazolium-based ionic liquid for the
      simultaneous determination of amlodipine and nimodipine in biological samples.
      Graphical abstract ?.

PMID- 30294764
TI  - Management of Late-Life Depression.
AB  - Depression is a common disorder in late life that is associated with poor quality
      of life, increased disability, and increased all-cause mortality. Rates of
      completed suicide are the highest in older depressed men compared with any other
      age group. In this age group, depression is often concurrent with medical illness
      and it can aggravate the course of medical illness. Cognitive impairment is
      frequently present and may be the result of the depression itself or may be the
      consequence of a neurodegenerative disorder such as Alzheimer's disease. Evidence
      based psychotherapies, antidepressants, and somatic treatments such as
      electroconvulsive therapy are employed in the treatment of older depressed
      adults. Treatment may be complicated by the presence of cognitive impairment,
      other comorbid medical disorders, and medications used to treat these disorders.
      Certain safety issues such as increased bleeding risk, hyponatremia, decreased
      bone density and falls may be associated with antidepressant treatment, may be
      more common in older depressed adults, and their consequences may be more severe
      in late life. These risks, however, need to be weighed against the hazards of
      untreated depression. With appropriate care, most older depressed patients can be
      successfully treated and a positive outcome can have a significant effect on the
      patient's quality of life.

PMID- 30294763
TI  - Diabetes and HIV.
AB  - PURPOSE OF REVIEW: This review seeks to address the epidemiology and
      pathophysiological basis of the interaction between HIV infection and diabetes
      and the implication for treatment. Its importance stems from the current context
      of the growing burden of both conditions and the possible mechanisms of
      interactions that may exist but not yet sufficiently examined. RECENT FINDINGS:
      HIV infection is associated with increased risk of insulin resistance, and ART is
      associated with metabolic derangement and the occurrence of type 2 diabetes. The
      increasing survival among people with HIV infection in developing countries is
      paralleled by a growing burden of chronic non-communicable diseases (NCDs)
      especially cardiovascular diseases and diabetes mellitus. The prevalence of
      diabetes mellitus is higher in HIV-positive persons compared to the general
      population, and especially those with associated hepatitis C virus (HCV) co
      infection. Antiretroviral therapy (ART) during chronic HIV infection is the most
      incriminated risk factor for the development of diabetes mellitus through diverse
      mechanisms depending on the ART leading to insulin resistance and increased
      inflammatory status. A staggering 629 million of people 20-79 years are projected
      to have diabetes by 2045 while the world will soon enter the fourth decade of the
      HIV infection. Classical risk factors for diabetes such as physical inactivity
      and unhealthy diet may not solely explain the current trends, suggesting the role
      of novel risk factors including infections/inflammation. HIV and its treatment
      have been identified as potential contributors. Co-infections frequently observed
      during HIV infection also significantly influence both the epidemiological and
      pathophysiological of the link between HIV and diabetes. Although the relative
      contribution of each risk factor has not yet been quantified, several lines of
      evidence suggest that ART is a major contributor to hyperglycemia in HIV
      infection. ARTs have also led to an increase in metabolic dysfunction, including
      insulin resistance syndromes, dyslipidemia, and lipodystrophy. The association
      between ARTs and the risk of developing diabetes therefore calls for a careful
      choice of medication and evaluation of the risk of developing diabetes.

PMID- 30294765
TI  - Neurostimulation Therapies.
AB  - Depression is one of the most disabling conditions in the world. In many cases
      patients continue to suffer with depressive disorders despite a series of
      adequate trials of medication and psychotherapy. Neuromodulation treatments offer
      a qualitatively different modality of treatment that can frequently prove
      efficacious in these treatment-refractory patients. The field of neuromodulation
      focuses on the use of electrical/electromagnetic energy, both invasively and
      noninvasively, to interface with and ultimately alter activity within the human
      brain for therapeutic purposes. These treatments provide another set of options
      to offer patients when clinically indicated, and knowledge of their safety, risks
      and benefits, and appropriate clinical application is essential for modern
      psychiatrists and other mental health professionals. Although neuromodulation
      techniques hold tremendous promise, only three such treatments are currently
      approved by the United States Food and Drug Administration (FDA) for the
      treatment of major depressive disorder: electroconvulsive therapy (ECT), vagus
      nerve stimulation (VNS), and repetitive transcranial magnetic stimulation (rTMS).
      Additionally, numerous other neurostimulation modalities (deep brain stimulation
      [DBS], magnetic seizure therapy [MST], transcranial electric stimulation [tES],
      and trigeminal nerve stimulation [TNS]), though currently experimental, show
      considerable therapeutic promise. Researchers are actively looking for ways to
      optimize outcomes and clinical benefits by making neuromodulation treatments
      safer, more efficacious, and more durable.

PMID- 30294766
TI  - The use of gasoline in a complex suicide.
AB  - This case represents a planned complex suicide in which the victim shot himself
      in the head after dousing his living quarters with gasoline. The spark induced
      ignition of gasoline vapors and led to an explosion. Liquid gasoline is not
      flammable, but the vapor/mixture of gases above the surface of the liquid is. In
      this case the victim might have counted on the resulting fire and/or explosion,
      but we are not able to tell that with certainty. We have assumed that the plan
      was for the gunshot to the head to lead to instantaneous death, and for the flame
      and/or explosion to lead to the destruction of the body. The explosion launched
      the body out of the apartment, meaning it did not get charred. It is also our
      assumption that the victim did not expect that the explosion would eject his body
      from the flames and lead to less severe burns than he had calculated, making this
      complex suicide "less successful" than he had planned.

PMID- 30294767
TI  - Incidence and costs of injuries to children and adults in the United States.
AB  - BACKGROUND: Injuries are a leading cause of death and acquired disability, and
      result in significant medical spending. Prior estimates of injury-related cost
      have been limited by older data, for certain population, or specific mechanisms.
      FINDINGS: This study estimated the incidence of hospital-treated nonfatal
      injuries in the United States (US) in 2013 and the related comprehensive costs.
      Injury-related emergency department (ED) visits and hospitalizations were
      identified using 2013 Healthcare Cost and Utilization Project (HCUP) data. Models
      estimated the costs of medical spending and lost future work due to injuries in
      2013 U.S. dollars. A total of 31,038,072 nonfatal injury-related hospitalizations
      and ED visits were identified, representing 9.8 per 100 people. Hospital-treated
      nonfatal injuries cost an estimated $1.853 trillion, including $168 billion in
      medical spending, $223 billion in work losses, and $1.461 trillion in quality of
      life losses. CONCLUSIONS: Approximately one in 10 individuals in the US is
      treated in the hospital for injury each year, with high corresponding costs.
      These data support priority-setting to reduce the injury burden in the US.

PMID- 30294768
TI  - Gastric Bypass as a Third Bariatric Procedure-Our Experience with 42 Cases.
AB  - BACKGROUND: It is not uncommon to encounter patients seeking a third, fourth, or
      even fifth bariatric procedure. With higher expected complication rates and
      questionable patient benefit, the indication for multiple revisions is still in
      doubt. To evaluate the perioperative and post-operative outcomes of patients
      undergoing gastric bypass after two previous bariatric surgeries or more.
      METHODS: We identified all patients that underwent gastric bypass following at
      least 2 previous bariatric surgeries. We looked at patient demographics, previous
      bariatric surgeries, pre-operative body mass index (BMI) and obesity-related co
      morbidities, perioperative complications, length of stay (LOS), re-admissions and
      re-operations, percentage of excess weight loss, and resolution or improvement in
      comorbidities. RESULTS: Forty-two patients met the inclusion criteria, the
      majority being females (31, 73.8%). Average age was 45.6 years (range 27-62),
      average weight and BMI was 116 kg (range 75-175 kg) and 41.1 kg/m2 (range 25.6
      58.7 kg/m2), respectively. Thirty-two patients had two previous bariatric
      surgeries (73.8%), and 10 patients had 3 former bariatric surgeries (23.8%), and
      for one patient, this was the fifth bariatric procedure (2.4%). Mean LOS was 10
      days (range 2-56 days). Eight patients (19%) needed re-admission and 5 (11.9%)
      needed re-operation. At a median follow up of 48 months (range 7-99 months), the
      average BMI was 34.5 kg/m2 (range 23.7-55.1 kg/m2) reflecting an excess BMI loss
      of 43.3%. CONCLUSIONS: Gastric bypass as a third or more bariatric procedure is
      effective yet associated with high complication rates, re-admissions, and re
      operations.

PMID- 30294769
TI  - The inflection point: a torque reference for lingual bracket positioning on the
      palatal surface curvature of the maxillary central incisor.
AB  - BACKGROUND: Contrary to buccal orthodontics, lingual orthodontics has no
      reference for vertical bracket positioning on the maxillary central incisor. The
      aim of this study was to provide a reference point in relation to torque for
      lingual bracket positioning on the palatal surface curvature (PSC) of the
      maxillary central incisor. METHODS: Cone beam computed tomography (CBCT)
      radiographs of 50 right maxillary central incisors from archives of a dental
      radiographic center were transferred to Photoshop, where their PSC was traced
      using pen-tool. The PSC torque angle values of the incisors were calculated in
      Excel using cubic poly-Bezier curves at 0.5-mm increments and at the inflection
      point of PSC. Descriptive statistics for the torque angle values of the
      increments and for the inflection point for the 50 incisors were then calculated.
      One-way ANOVA test was used to detect systematic differences between the
      increments, and Tukey test was used post-hoc. RESULTS: For all incisors,
      increments incisal to inflection point exhibited progressive decrease in torque
      angle values from the first-calculated increment to inflection point while
      increments cervical to inflection point exhibited progressive increase from
      inflection point to last-calculated increment. Mean torque angle values of all
      the increments and inflection point showed high standard deviations and vast
      range of values. One-way ANOVA test was highly statistically significant (p <
      0.0001) and most pairwise comparisons of the increments using Tukey test were
      significant. CONCLUSIONS: Inflection point can be used as a reference for bracket
      positioning on PSC. Cervically oriented shifts in vertical bracket position cause
      crown labial/root palatal movement cervical to inflection point and crown
      palatal/root labial movement incisal to it. A scientific mathematical
      justification for customized bracket torque prescriptions on PSC of maxillary
      central incisor was also provided.

PMID- 30294770
TI  - Correction to: Jeger V, et al. Is there a role for procalcitonin in
      differentiating uncomplicated and complicated diverticulitis in order to reduce
      antibiotic therapy?

PMID- 30294771
TI  - Effects of maternal caffeine consumption on the breastfed child: a systematic
      review.
AB  - BACKGROUND: Nutrition in the first 1000 days between pregnancy and 24 months of
      life is critical for child health, and exclusive breastfeeding is promoted as the
      infant's best source of nutrition in the first 6 months. Caffeine is a central
      nervous system stimulant occurring naturally in some foods and used to treat
      primary apnoea in premature babies. However high caffeine intake can be harmful,
      and caffeine is transmitted into breastmilk. AIM: To systematically review the
      evidence on the effects of maternal caffeine consumption during breastfeeding on
      the breastfed child. METHOD: A systematic search was conducted to October 2017 in
      MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane Library. The British
      Library catalogue, which covers doctoral theses, was searched and PRISMA
      guidelines followed. Two reviewers screened for experimental, cohort, or case
      control studies and performed independent quality assessment using the Newcastle
      Ottawa scale. The main reviewer performed data extraction, checked by the second
      reviewer. RESULTS: Two cohort, two crossover studies, and one N-of-1 trial were
      included for narrative synthesis. One crossover and two cohort studies of small
      sample sizes directly investigated maternal caffeine consumption. No significant
      effects on 24-hour heart rate, 24-hour sleep time, or frequent night waking of
      the breastfed child were found. One study found a decreased rate of full
      breastfeeding at 6 months postpartum. Two studies indirectly investigated
      caffeine exposure. Maternal chocolate and coffee consumption was associated with
      increased infant colic, and severe to moderate exacerbation of infant atopic
      dermatitis. However, whether caffeine was the causal ingredient is questionable.
      The insufficient and inconsistent evidence available had quality issues impeding
      conclusions on the effects of maternal caffeine consumption on the breastfed
      child. CONCLUSION: Evidence for recommendations on caffeine intake for
      breastfeeding women is scant, of limited quality and inconclusive. Birth cohort
      studies investigating the potential positive and negative effects of various
      levels of maternal caffeine consumption on the breastfed child and breastfeeding
      mother could improve the knowledge base and allow evidence-based advice for
      breastfeeding mothers. Systematic review registration number: CRD42017078790.

PMID- 30294772
TI  - Rethinking hospitalisations for substance use disorders.

PMID- 30294773
TI  - The immune influence of a parabiosis model on tumour-bearing mice.
AB  - AIM: The aim of this study was to analyse the immune influence of a parabiosis
      model on tumour-bearing mice. METHODS: Parabiosis was established between C57BL/6
      wild-type mice expressing green fluorescent protein (GFP+) and C57BL/6 wild-type
      mice without green fluorescent protein (GFP?) to ensure blood cross-circulation
      between animals, and then the expression of CD4+ T cells, CD8+ T cells and
      interleukins 2, 4 and 10, and interferon-gamma (INF-gamma) in spleen cells of
      parabiosis model mice were examined with flow cytometry. At day 8 and day 14
      after conjoined surgery, we were aiming to sample tumour tissue in the parabiosis
      mice and observe changes of CD3, CD4, CD8, CD31, IFN-gamma and vascular
      endothelial growth factor (VEGF) through immunohistochemical analysis. RESULTS:
      The interaction of blood was established on the third day with modelling rate of
      85.7% after blood interaction. The healthy cells of GFP+ C57 mice entered the
      blood circulation of tumour-bearing mice via a connecting capillary network,
      playing a role in stimulating CD4+ and CD8+ cells in the tumour-bearing mice so
      that CD4+ cells increased more in tumour-bearing mice than in the positive
      control group (p <0.05). The number of GFP+ cells that were detected in a tumour
      bearing mouse was small, but GFP+ cells can stimulate the mouse itself to
      generate more CD4+/interleukin (IL)-4, CD4+/IL-10 (p <0.05).The numbers of
      CD4+/IL-2, CD4+/IL-4 and CD4+/IL-10 among the GFP+ mice were higher than those in
      the negative control group(p <0.05).The levels of IFN-gamma in both mice in the
      parabiosis model were decreased (p <0.05). The rate of CD4+/CD8+ in parabiosis
      GFP+ mice was higher than in the negative control group (p <0.05). In
      immunohistochemical tests, the rates of CD3, CD4, CD8 and IFN-gamma positive
      cells was higher than in the positive control group, with their optical densities
      of 0.32 +/- 0.63, 0.33 +/- 0.00, 0.31 +/- 0.91 and 0.28 +/- 0.14 respectively (p
      <0.05). The expression of CD31 (0.19 +/- 0.50) and VEGF (0.19 +/- 0.21) were
      lower when compared with the positive control group, with no significant
      difference. CD31 and VEFG cell expression was low, at 0.19 +/- 0.50 and 0.19 +/-
      0.21, respectively, compared with the positive control group (p >0.05). Values
      for CD31 and VEGF cells in the positive control group were higher, at 0.32 +/-
      0.35 and 0.29 +/- 0.35, respectively, but when compared with the parabiosis
      tumour-bearing group, there was no significant difference. The expression of CD3,
      CD4, CD8 and IFN-gamma cells at day 8 was low: 0.22, 0.17, 0.15 and 0.16,
      respectively. When compared with the parabiosis tumour-bearing group, there was
      no significant difference. CONCLUSIONS: The established allogeneic parabiosis
      mice model can be well adapted to the conjoined state of mice and be applied in
      wide medical experiments. The parabiosis model has played an important role in
      studying immune regulation, which provides a basis for the future tumour
      immunotherapy. Parabiosis models can stimulate tumour-bearing mice to generate
      CD3, CD4, CD8 and IFN-gamma, and play a notable role in immune regulation and
      tumour destruction. The positive expression rates of CD31 and VEFG cells in the
      parabiosis tumour-bearing group were lower; however, when compared with the
      positive control group, there was no significant difference.

PMID- 30294774
TI  - Semispecific TPPII inhibitor Ala-Ala-Phe-chloromethylketone (AAF-cmk) displays
      cytotoxic activity by induction of apoptosis, autophagy and protein aggregation
      in U937 cells.
AB  - INTRODUCTION: The main component of extralysosomal proteolysis is the ubiquitin
      proteasome system (UPS), which is supplemented by tripeptidyl peptidase II
      (TPPII). That system is a target for anticancer strategies by using proteasome
      inhibitors. Data from several studies on leukemic cells share evidence for the
      beneficial and potential role of TPPII in cell survivability. Therefore, the aim
      of this work was to analyze the effect of AAF-cmk, a membrane permeable semi
      specific TPPII inhibitor, on human monocytic leukemic cells U937 for
      translational research. MATERIAL AND METHODS: We studied the viability of U937
      cells incubated with AAF-cmk using tetrazolium salt reduction assay (MTT) and
      apoptosis induction by assessing caspase activation by Western blotting and
      Annexin V binding assays. Transmission electron microscopy (TEM), a gold standard
      for apoptosis and autophagy detection, was used to assess the ultrastructure of
      U937 cells. RESULTS: Incubation of cells with AAF-cmk reduced their viability and
      induced apoptosis by intrinsic pathway. In groups treated with AAF-cmk,
      activation of caspases 9 and 3 was observed and caspase inhibition by zVDA
      restored cell viability. TEM revealed the presence of ultrastructural features of
      apoptosis. Moreover, we identified two types of protein aggregates. The first one
      was found in close proximity to the endoplasmic reticulum (ER) and corresponds to
      Aggresome-Like Structure (ALIS); however, the second novel type of aggregate was
      not related to ER-elements, but rather to free cytosolic ribosomes. This type did
      not correspond to the aggresome neither in localization nor the structure, thus
      we referred these aggregates as ALiSNER (Aggresome-Like Structure Not Associated
      with the ER). CONCLUSIONS: Our results provide novel and important findings about
      the role of TPPII in protein homeostasis and cell survival. Since semispecific
      TPPII inhibitor AAF-cmk displays cytotoxic activity against leukemic U937 cells
      in vitro it can be considered as a potential anticancer agent.

PMID- 30294775
TI  - Dealing with a first seizure: accurate diagnosis and good management.

PMID- 30294776
TI  - Self-care and manual ability in preschool children with cerebral palsy: a
      longitudinal study.
AB  - AIM: To describe longitudinal development of self-care and its relationship to
      manual ability in children with cerebral palsy (CP) aged 18 months to 5 years
      across all functional abilities. METHOD: This was a prospective longitudinal
      population-based study of 290 children with CP (178 [61%] males, 112 [39%]
      females). Self-care was assessed using the Pediatric Evaluation of Disability
      Inventory (PEDI). At 60 months (n=242), children were classified using the Manual
      Ability Classification System (MACS); 113 in level I (47%), 61 in MACS level II
      (25%), 24 in MACS level III (10%), 14 in MACS level IV (6%), and 30 in MACS level
      V (12%). Measures were taken at 18 months, 24 months, 30 months, 36 months, 48
      months, and 60 months of age. Longitudinal analyses were performed using mixed
      effects linear regression models. RESULTS: Self-care development achieved by 60
      months was negatively associated with the severity of manual ability impairment.
      Distinct self-care developmental trajectories were found with estimated changes
      in PEDI self-care scaled scores per month: 0.61 for MACS level I, 0.46 for MACS
      levels II, 0.31 for MACS level III, 0.16 for MACS level IV, and 0.03 for MACS
      level V. Children classified in MACS level V had the lowest level of self-care
      skills at 18 months and showed no progress in self-care development.
      INTERPRETATION: This study reports rate of self-care development in preschool
      children with CP. Self-care performance was highest in children with greatest
      manual ability. Clinicians may use rates of change to predict or monitor self
      care performance. PEDI trajectories inform goal setting in discussions with
      families regarding expected levels of independence in self-care. WHAT THIS PAPER
      ADDS: Distinct self-care developmental trajectories in children with cerebral
      palsy were found according to Manual Ability Classification System (MACS) levels.
      Children in MACS levels IV and V with epilepsy did not show any significant
      change in self-care. Children in MACS levels IV and V without epilepsy
      demonstrated small yet significant gains in self-care performance.

PMID- 30294777
TI  - Predictive validity of the General Movements Assessment: type of population
      versus type of assessment.

PMID- 30294778
TI  - Very early diagnosis of autism spectrum disorder.

PMID- 30294779
TI  - Protecting the developing brain: empowering child neurologists to become more
      preventative.

PMID- 30294780
TI  - The effect of political control on financial performance, structure, and outcomes
      of US nursing homes.
AB  - OBJECTIVE: To evaluate the effect of partisan political control on financial
      performance, structure, and outcomes of for-profit and not-for-profit US nursing
      homes. DATA SOURCES/STUDY SETTING: Nineteen-year panel (1996-2014) of state
      election outcomes, financial performance data from nursing home cost reports,
      operational and aggregate resident characteristics from OSCAR of 13 737 nursing
      homes. STUDY DESIGN: A linear panel model was estimated to identify the effect of
      Democratic and Republican political control on next year's outcomes. Nursing home
      outcomes were defined as yearly facility revenues, expenses, and profits; the
      number of Medicaid, Medicare, and private-pay residents; staffing levels; and
      selected resident outcomes. PRINCIPAL FINDINGS: Democratic political control
      leads to an increase in financial flows to for-profit nursing homes, boosting
      profits without producing observable improvements in resident outcomes.
      Republican political control leads to lower revenues and profits of for-profit
      nursing homes. A shift from Medicaid to more profitable private-pay residents
      following Republican political control is observed for all nursing homes.
      Financial performance of not-for-profit nursing homes is not significantly
      affected by changes in political control. CONCLUSION: Political control of the
      two legislative chambers-but not of the governorship-shapes the structure of the
      nursing home industry as seen in provider behavior.

PMID- 30294781
TI  - Improvement of alopecia areata with apremilast.

PMID- 30294782
TI  - Chondrodysplasia punctata (CDPX2) in a male caused by single-gene mosaicism: A 20
      year follow-up.

PMID- 30294783
TI  - Family-centred health care for children with cerebral palsy.
AB  - AIM: To identify characteristics of young children with cerebral palsy (CP), and
      intrinsic and extrinsic factors, that may be associated with parental perceptions
      regarding family-centred health care services. METHOD: We conducted a cross
      sectional study, drawing our sample from the Canadian Cerebral Palsy Registry
      (CCPR). Parents rated the extent of family-centred care provided by their child's
      health care teams using the 56-item Measures of Process of Care (MPOC)
      questionnaire. Environmental and CP phenotypic variables were extracted from the
      CCPR for group comparisons. Low and high MPOC-56 raters were also compared.
      RESULTS: Valid responses were obtained from 282 families (90%). All MPOC-56
      subscales were highly rated (median >=6.0), indicating satisfaction with health
      care services, with the exception of the Providing General Information subscale
      (median 4.8, interquartile range 3.2-6.0). Parents from Nova Scotia rated all
      subscales significantly higher than parents from other regions. CP subtype and
      severity were not significantly associated with MPOC-56 subscale scores. Higher
      socio-economic status was associated with lower MPOC-56 subscale scores. Higher
      paternal educational attainment and household income were significantly
      associated with lower scores on the Providing General Information and Providing
      Specific Information about the Child subscales respectively. INTERPRETATION:
      Participants affirmed the provision of family-centred services from Canadian
      pediatric rehabilitation centres. Sociodemographic factors were associated with
      parental perceptions of family-centred services. WHAT THIS PAPER ADDS:
      Sociodemographic factors were associated with parental perceptions of family
      centred care. Factors intrinsic to the child's cerebral palsy were not associated
      with parental perceptions.

PMID- 30294784
TI  - Rehospitalizations for complications and mortality following pacemaker
      implantation: A retrospective cohort study in an older population.
AB  - INTRODUCTION: A large number of older people receive pacemakers each year but
      broad population-based studies that describe complications following pacemaker
      implantation in this population are lacking. METHODS: We conducted a
      retrospective cohort study using data from the Australian Government Department
      of Veterans' Affairs database. The cohort consisted of patients who received a
      pacemaker from 2005 to 2014. The outcomes were subsequent rehospitalizations for
      infections, procedure-related complications, thromboembolism, cardiovascular
      events (heart failure, myocardial infarction, and atrial fibrillation), and
      reoperation of pacemaker, and mortality. RESULTS: There were 10 883 pacemakers
      recipients, the median age was 86 years (interquartile range 83-89), 61% were
      males, and 74% received a dual-chamber pacemaker. Within 90 days postdischarge,
      rehospitalizations were occasioned by pacemaker infection in 0.5%, device-related
      complications in 1.5%, cerebral infarction in 0.7%, and heart failure in 6% of
      single-chamber pacemaker recipients. In dual-chamber pacemaker recipients
      rehospitalizations were occasioned by pacemaker infection in 0.4%, septicemia in
      0.4%, device-related complications in 1.2%, cerebral infarction in 0.3%, and
      heart failure in 3%. Rehospitalizations for pacemaker adjustment occurred in 1.5%
      of patients. The 90-day postdischarge mortality was 5% and 3% in patients with
      single- and dual-chamber pacemaker, respectively. CONCLUSION: Rehospitalizations
      for infection, procedure-related complications, or thromboembolism occurred in 1%
      to 2% of patients within 90 days postdischarge, while 10% of single chamber and
      7% of dual-chamber recipients experienced a rehospitalization for a
      cardiovascular event.

PMID- 30294785
TI  - Serological and genetic characterization of Flavobacterium psychrophilum isolated
      from farmed salmonids in Turkey.
AB  - Turkey was the largest rainbow trout producer of the European countries in 2016,
      and the reason for this production is mainly attributed to its egg and fry
      production. Flavobacterium psychrophilum cause the highest rates of mortality in
      the starting to feeding stages of the fish. In the present study, twenty-five F.
      psychrophilum isolates recovered from rainbow trout, coruh trout and brook trout
      were analysed by RAPD-PCR, ERIC-PCR, REP-PCR and PCR-RFLP, including 16S rRNA,
      gyrA and gyrB gene regions and PCR-based serotyping method. The PCR-based
      molecular analysis showed that the isolates could not be differentiated exactly
      according to isolation source and geographical region. Most isolates were of type
      1 and type-2, and some of them were of type-0 and type-3; in addition, one
      isolate showed a unique serotype. The combined analysis results showed that F.
      psychrophilum isolates discriminated as five different genotypes and all isolates
      were successfully discriminated based on host.

PMID- 30294786
TI  - International validation of harmonized definitions for complications of blood
      donations.
AB  - BACKGROUND: In December 2014, a multinational collaboration of hemovigilance
      experts from the International Society of Blood Transfusion (ISBT), the
      International Hemovigilance Network, and AABB published harmonized definitions of
      complications related to blood donation titled "Standard for Surveillance of
      Complications Related to Blood Donation." Both mandatory and optional terms were
      included. The definitions are endorsed by the Alliance of Blood Operators and the
      European Blood Alliance. STUDY DESIGN AND METHODS: The objective of this study
      was to validate harmonized donor hemovigilance definitions with potential users.
      In June 2016, 30 real-world cases were sent to potential users around the world
      along with the definitions, an answer sheet, and instructions on how to complete
      the validation exercise. RESULTS: Overall, 54 responses from 25 countries were
      received, including over 400 comments. The results were presented for feedback at
      both ISBT and AABB meetings. Case diagnoses were consistent across most
      responders. Exceptions were rare adverse events, nonstandard presentations, or
      incomplete information. In general, the application of optional definitions,
      including severity grading and imputability, had the most variability.
      CONCLUSION: The use of standardized terms in the donor setting serves to increase
      focus on donor safety, facilitate conversation, foster exchange of information,
      and frame questions for future research. Overall, the definitions provide
      adequate coverage of donor reactions; however, some terms require clarification.
      Severity grading and imputability and other optional terms need clear and
      objective definitions and instructions on when and how to use them. Additional
      feedback and final recommendations are summarized in this report.

PMID- 30294787
TI  - Segmental morphometrics of bonobos (Pan paniscus): are they really different from
      chimpanzees (Pan troglodytes)?
AB  - The inertial properties of body segments reflect performance and locomotor habits
      in primates. While Pan paniscus is generally described as more gracile, lighter
      in body mass, and as having relatively longer and heavier hindlimbs than Pan
      troglodytes, both species exhibit very similar patterns of (quadrupedal and
      bipedal) kinematics, but show slightly different locomotor repertoires. We used a
      geometric model to estimate the inertial properties for all body segments (i.e.
      head, trunk, upper and lower arms, hand, thigh, shank and foot) using external
      length and diameter measurements of 12 anaesthetized bonobos (eight adults and
      four immatures). We also calculated whole limb inertial properties. When we
      compared absolute and relative segment morphometric and inertial variables
      between bonobos and chimpanzees, we found that adult bonobos are significantly
      lighter than adult chimpanzees. The bonobo is also shorter in head length, upper
      and lower arm lengths, and foot length, and is generally lighter in most absolute
      segment mass values (except head and hand). In contrast, the bonobo has a longer
      trunk. When scaled relative to body mass, most differences disappear between the
      two species. Only the longer trunk and the shorter head of the bonobo remain
      apparent, as well as the lighter thigh compared with the chimpanzee. We found
      similar values of natural pendular periods of the limbs in both species, despite
      differences in absolute limb lengths, masses, mass centres (for the hindlimb) and
      moments of inertia. While our data contradict the commonly accepted view that
      bonobos have relatively longer and heavier hindlimbs than chimpanzees, they are
      consistent with the observed similarities in the quadrupedal and bipedal
      kinematics between these species. The morphological differences between both
      species are more subtle than those previously described from postcranial
      osteological materials.

PMID- 30294788
TI  - Post-metamorphic ontogeny of Zoroaster fulgens Thomson, 1873 (Asteroidea,
      Forcipulatacea).
AB  - The complete ontogenetic development of an asteroid skeleton has never been
      described formally for any species. Here, we describe in detail the post
      metamorphic ontogeny of Zoroaster fulgens Thomson, 1873. The major novelty of our
      work is the description of patterns of plate addition, the ontogeny of the
      internal ossicles, as well as the variability of ossicles according to their
      position along series. Seven specimens collected in the Rockall Basin (North
      Atlantic) were dissected with bleach and their anatomy was documented using a
      scanning electron microscope. The external anatomy was additionally observed on
      more than 30 specimens. We found that the overall structure of the skeleton does
      not change much between juveniles and adults, but the shape of individual ossicle
      changes during growth. Allometric scaling was particularly visible on the orals,
      ambulacrals and adambulacrals. The shape of an ossicle is more dependent of its
      position along the arm series than of its individual size. Many morphological
      features differentiate progressively during ontogeny, while others are expressed
      consistently among specimens. The study of this ontogenetic series allows
      discussing the homology between the structures present on the ossicles of Z.
      fulgens in particular and other forcipulatacean sea stars in general (i.e.
      muscles insertions and articulation areas). The new data obtained in this study
      provide a comprehensive framework of the anatomy and ontogeny of Z. fulgens that
      will help resolve taxonomic and phylogenetic controversies in the future.

PMID- 30294790
TI  - Comparison of short-term complications between unilateral and single-session
      bilateral surgery for medial patellar luxation in small/medium breed dogs.
AB  - OBJECTIVES: To compare the short-term complications of unilateral versus single
      session bilateral medial patellar luxation surgery in small dogs. MATERIALS AND
      METHODS: The medical records of dogs weighing less than 13?6 kg that underwent
      medial patellar luxation surgery were reviewed. Dogs were included in one of two
      groups based on the type of surgery performed (unilateral or single-session
      bilateral). Postoperative patellar luxation grade and complications were compared
      between the groups. RESULTS: Two hundred and fifty-one dogs were included. In the
      bilateral treatment group, there was less improvement in patellar luxation grade
      and postoperative medial patellar luxation grade was higher. The frequency of
      major complications was higher in the bilateral group (23%) compared with the
      unilateral group (12%). CLINICAL SIGNIFICANCE: Single-session bilateral medial
      patellar luxation surgery was associated with a higher complication rate compared
      to unilateral surgery in this non-randomized observational study. Staged rather
      than single-session bilateral surgery should be considered in dogs with bilateral
      medial patellar luxation to improve clinical outcome and reduce the chance of
      major complications.

PMID- 30294791
TI  - Hypopigmented patches in childhood: do not forget mycosis fungoides.

PMID- 30294789
TI  - The development of the cloaca in the human embryo.
AB  - Subdivision of cloaca into urogenital and anorectal passages has remained
      controversial because of disagreements about the identity and role of the septum
      developing between both passages. This study aimed to clarify the development of
      the cloaca using a quantitative 3D morphological approach in human embryos of 4
      10 post-fertilisation weeks. Embryos were visualised with Amira 3D-reconstruction
      and Cinema 4D-remodelling software. Distances between landmarks were computed
      with Amira3D software. Our main finding was a pronounced difference in growth
      between rapidly expanding central and ventral parts, and slowly or non-growing
      cranial and dorsal parts. The entrance of the Wolffian duct into the cloaca
      proved a stable landmark that remained linked to the position of vertebra S3.
      Suppressed growth in the cranial cloaca resulted in an apparent craniodorsal
      migration of the entrance of the Wolffian duct, while suppressed growth in the
      dorsal cloaca changed the entrance of the hindgut from cranial to dorsal on the
      cloaca. Transformation of this 'end-to-end' into an 'end-to-side' junction
      produced temporary 'lateral (Rathke's) folds'. The persistent difference in
      dorsoventral growth straightened the embryonic caudal body axis and concomitantly
      extended the frontally oriented 'urorectal (Tourneux's) septum' caudally between
      the ventral urogenital and dorsal anorectal parts of the cloaca. The dorsoventral
      growth difference also divided the cloacal membrane into a well-developed ventral
      urethral plate and a thin dorsal cloacal membrane proper, which ruptured at 6.5
      weeks. The expansion of the pericloacal mesenchyme followed the dorsoventral
      growth difference and produced the genital tubercle. Dysregulation of dorsal
      cloacal development is probably an important cause of anorectal malformations:
      too little regressive development may result in anorectal agenesis, and too much
      regression in stenosis or atresia of the remaining part of the dorsal cloaca.

PMID- 30294792
TI  - Systematic review with meta-analysis: the efficacy of prebiotics, probiotics,
      synbiotics and antibiotics in irritable bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a chronic functional bowel
      disorder. Disturbances in the gastrointestinal microbiome may be involved in its
      aetiology. AIM: To perform a systematic review and meta-analysis to examine the
      efficacy of prebiotics, probiotics, synbiotics and antibiotics in IBS. METHODS:
      MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to
      July 2017). Randomised controlled trials (RCTs) recruiting adults with IBS,
      comparing prebiotics, probiotics, synbiotics or antibiotics with placebo or no
      therapy were eligible. Dichotomous symptom data were pooled to obtain a relative
      risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval
      (CI). Continuous data were pooled using a standardised mean difference with a 95%
      CI. RESULTS: The search identified 4017 citations. Data for prebiotics and
      synbiotics were sparse. Fifty-three RCTs of probiotics, involving 5545 patients,
      were eligible. Particular combinations of probiotics, or specific species and
      strains, appeared to have beneficial effects on global IBS symptoms and abdominal
      pain, but it was not possible to draw definitive conclusions about their
      efficacy. There were five trials of similar design that used rifaximin in non
      constipated IBS patients, which was more effective than placebo (RR of symptoms
      persisting = 0.84; 95% CI 0.79-0.90). Adverse events were no more common with
      probiotics or antibiotics. CONCLUSIONS: Which particular combination, species or
      strains of probiotics are effective for IBS remains, for the most part, unclear.
      Rifaximin has modest efficacy in improving symptoms in non-constipated IBS.

PMID- 30294793
TI  - Asymptomatic solitary mass on the sacral region.
AB  - Nuchal-type fibroma (NTF) is a rare, benign, tumour-like fibrous proliferation of
      unknown pathogenesis. Despite the name, approximately one-third of cases occur at
      extranuchal sites. We report a rare case of NTF of the sacral region, an
      extremely uncommon extranuchal site. As NTF is often misdiagnosed because of its
      rarity and histopathological similarity with other fibrous tumours, we present
      this case to increase understanding of this rare disease entity.

PMID- 30294794
TI  - Invasion and migration of MDA-MB-231 cells are inhibited by block of AhR and
      NFAT: role of AhR/NFAT1/beta4 integrin signaling.
AB  - Benzo[alpha]pyrene (BaP) can have significant role in the development of breast
      cancer via aryl hydrocarbon receptor (AhR) activation. AhR activation has been
      studied in several functions such as survival, migration and invasion of cancer
      cells. In cancer, integrins contribute to the migration/invasion process and are
      regulated by nuclear factor of activated T cells (NFAT) and transforming growth
      factor (TGF) beta pathways. The aim of the present study was to examine the
      effect of BaP, an activator of AhR and cyclosporine A (CsA), as inhibitor of NFAT
      on migration and invasion of MDA-MB-231 cells. Furthermore, the effects of BaP
      and CsA were evaluated regarding the crosstalk of AhR, NFAT1 and TGF-beta
      receptor 1 signaling. Treatment of MDA-MB-231 with BaP resulted in significantly
      more live cells in low doses; however, blocking NFAT with CsA decreased the
      viability of the cells. Activation of AhR by BaP induced invasion as well as
      migration in MDA-MB-231 cells, which was blocked by AhR antagonist. Unlike BaP,
      block of NFAT with CsA inhibited cell migration and cell invasion. In these
      cells, BaP significantly reduced AhR expression while this reduction was reversed
      by CH-223191; however, CsA treatment lowered the AhR expression only at low dose.
      The level of beta4 integrin was significantly reduced by CsA at 1 and 2.5 MUm.
      Protein levels of Snail and TGF-beta receptor 1 were not significantly altered by
      BaP and CsA treatments. Considering these findings, the low AhR expression and
      high beta4 integrin level following BaP and/or CsA treatments may contribute to
      the higher invasion/migration in MDA-MB-231 cells.

PMID- 30294795
TI  - A Potential Pitfall of Using Focused Assessment With Sonography for Trauma in
      Pediatric Trauma.
AB  - Prospective studies have shown sensitivities of 73% to 88% and specificities of
      98% to 100% for using the focused assessment with sonography for trauma (FAST)
      examination to identify free fluid in adult trauma patients. However, the
      efficacy of FAST examinations for pediatric trauma patients has not been well
      defined, and studies looking at diagnostic performance have had varied results.
      We describe 3 cases of the potential pitfalls of the pediatric FAST examination
      in pediatric trauma patients using an advanced-processing ultrasound machine. We
      hypothesize several etiologies for these false-positive findings in the setting
      of advanced image-processing capabilities of point-of-care ultrasound. We also
      discuss the reevaluation of clinical algorithms and interpretation practices when
      using the FAST examination in pediatric trauma.

PMID- 30294796
TI  - Proteomic fingerprinting of apple fruit, juice, and cider via combinatorial
      peptide ligand libraries and MS analysis.
AB  - Combinatorial peptide ligand libraries coupled to MS was applied to extensively
      map the proteome of apple fruit, and to detect its presence in commercial apple
      juice and cider to evaluate their authenticity and genuineness. Using the
      Uniprot_Malus database, 96 proteins were detected in apples, among which 30
      proteins were specifically captured via combinatorial peptide ligand libraries.
      Next, three proteins, previously recognized in fruits, were found in apple juice,
      which were involved in cellular metabolism of fruit maturation and in allergenic
      reactions. On the other hand, only one Malus allergen was identified in cider
      beads eluate, demonstrating that the industrial processes did not prevent any
      negative effects in sensitive subjects. Thus, the present study not only
      increases the knowledge of the apple proteome but also offers a reliable
      analytical method to assess quality and genuineness of commercial products, which
      could be also used to inform consumers about the presence of allergens.

PMID- 30294797
TI  - A method for quantitative 2-dimensional sonographic analysis of the fetal conus
      medullaris position.
AB  - OBJECTIVE: This study explored the use of 2-dimensional (2D) ultrasound scans for
      the quantitative assessment of the fetal conus medullaris (CM) position and its
      correlation with gestational age (GA). METHODS: This was a prospective study. We
      identified the first sacral vertebra (S1) by intersection of 2 lines in 2D scans,
      then counted upward from S1 to determine the CM level and recorded the number of
      ossified sacral vertebral bodies. A quantitative assessment of the CM position
      was performed by measuring the distance between the CM and the midpoint of the S1
      (CM-S1). The correlation between the CM-S1 distance and GA was evaluated.
      RESULTS: We determined the CM level by identifying S1 first in 521 fetuses (GA,
      20-38 weeks). The CM position in 70% of cases was at the L2 and L2-3 level, and
      at the L2 level or above after 37 weeks. The number of ossified sacral veterbral
      bodies was not consistent. CM-S1 measurements were easy to perform. A significant
      positive correlation between CM-S1 distance and GA was observed (R2  = .89, P <
      .05). The best-fit formula was: CM-S1 distance = 1.57 * GA - 16.43. The normal
      reference range was established and the fifth percentile was calculated for each
      GA. CONCLUSIONS: S1 was easily identified, and the CM position relative to S1 was
      useful. There was a substantial correlation between CM-S1 and GA. Below the fifth
      percentile it was suggested that tethered cord may exist.

PMID- 30294798
TI  - Chronic exposure to perfluorononanoic acid impairs spermatogenesis,
      steroidogenesis and fertility in male mice.
AB  - Perfluoroalkyl acids (PFAAs) are widely used in commercial applications and that
      they are ubiquitous and persistent in the environment. Perfluorononanoic acid
      (PFNA), a member of PFAAs, has been detected in human and wildlife. Previous
      acute exposure studies have shown the adverse effect of PFNA on the testis. The
      present study was aimed to examine the effect of chronic PFNA exposure, from
      prepuberty to adulthood, on testicular functions and fertility in Parkes (P) male
      mice and to investigate the possible mechanism(s) of its action. PFNA (0.2 and
      0.5 mg/kg) was orally administered to P male mice for 90 days from prepuberty
      (postnatal day [PND] 25) to adulthood (PND 114). Histologically, testes in PFNA
      treated mice showed non-uniform degenerative changes in the seminiferous tubules.
      The treatment also had adverse effects on testicular expression of steroidogenic
      markers, serum levels of cholesterol and testosterone, sperm parameters and on
      litter size. A marked increase in the level of lipid peroxidation and decrease in
      the activities of antioxidant enzymes were observed in the testis of PFNA-treated
      mice compared to controls. Further, a significant decrease in expression of
      proliferating cell nuclear antigen (PCNA) and in the number of PCNA-positive
      cells, and an increase in expression of caspase-3 were also noted in PFNA-treated
      mice testis. In conclusion, the results suggest that chronic exposure to PFNA in
      male mice interferes with testosterone biosynthesis and causes oxidative stress
      in the testis, leading to alterations in spermatogenesis, sperm quality and
      fertility potential.

PMID- 30294799
TI  - Long non-coding MEG3 is a marker for skeletal muscle development and meat
      production traits in pigs.
AB  - Long non-coding RNAmaternally expressed gene 3 (lncRNAMEG3) plays an important
      role in mammalian muscle development. Our previous transcriptome study showed
      that lncRNAMEG3 is differentially expressed during postnatal skeletal muscle
      development in pigs. The objective of the present study was to analyse the role
      of lncRNAMEG3 in prenatal and postnatal skeletal muscle development and
      investigate the association of MEG3 with meat production traits in pigs. We
      investigated the sequence conservation and temporal-spatial expression of
      lncRNAMEG3 and identified its core promoter and single nucleotide polymorphisms
      (SNPs). Our results show that MEG3 is conserved among pig, human and mouse and is
      expressed in a tissue-specific manner with high expression levels in kidney and
      leg and dorsal muscles. In addition, MEG3 is more abundant in prenatal muscle
      compared to postnatal muscle, and its expression peaks at gestational day 60.
      Notably, we observed almost no expression 40 days after birth. The core promoter
      of MEG3 is located upstream of the transcription initiation site between -447 and
      -40 bp. In our SNP linkage disequilibrium and association analyses, four of the
      10 potential polymorphism sites were found to be associated with corrected back
      fat thickness and age to reach 100 kg (rs325797437, rs344501106, rs81286029 and
      rs318656749). In addition, three haplotypes were found to be associated with
      differences in corrected age to reach 100 kg (AAAT, AAAT/GGGC, GAAT/GGGC). Our
      results indicate that MEG3 regulates skeletal muscle development and is a
      candidate gene for improving meat production traits in pigs.

PMID- 30294800
TI  - Corneal Confocal Microscopy: Neurologic Disease Biomarker in Friedreich's Ataxia.

PMID- 30294801
TI  - RNA-based markers in biopsy cores with atypical small acinar proliferation:
      Predictive effect of T2E fusion positivity and MMP-2 upregulation for a
      subsequent prostate cancer diagnosis.
AB  - BACKGROUND: Atypical small acinar proliferation (ASAP) is a precursor lesion of
      prostate cancer (PC), and PC develops from this suspicious focus or an unsampled
      malignant gland nearby. However, PC-related molecular alterations that could
      guide the timing of repeat biopsies and help monitor PC risk in ASAP-diagnosed
      patients have not been investigated. The purpose of this study was to first
      investigate the expression of seven different PC-related RNAs that included
      serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG) gene
      (TMPRSS2-ERG, T2E) fusion, alpha-methylacyl-CoA racemase (AMACR), kallikrein
      related peptidase 3 (KLK3), androgen receptor (AR), prostate cancer specific
      antigen 3 (PCA3), and matrix metalloproteinases (MMP)-2 and 9. METHODS: PC
      related RNAs were evaluated using a real-time quantitative reverse transcription
      polymerase chain reaction (RT-qPCR) system in pathologically ASAP-diagnosed
      prostate biopsy cores from 55 patients presenting with a normal digital rectal
      examination and a PSA level of 4-10 ng/mL. RESULTS: We detected that positive T2E
      fusion status (P = 0.013) and the expression of AMACR (P = 0.016), AR (P = 0.016)
      and MMP-2 (P = 0.013) were independently and significantly associated with PC
      risk in ASAP patients. There were also several statistically significant
      correlations between expression levels. Additionally, we demonstrated that T2E
      fusion positive ASAP patients with higher MMP-2 expression were more likely to be
      diagnosed with PC at a subsequent biopsy during the follow-up period (P = 0.003).
      CONCLUSIONS: Although, more clinical validations are needed for the
      stratification of PC risk in ASAP-diagnosed biopsy cores, our current results
      indicate that the coexistence of T2E fusion positivity with MMP-2 upregulation
      may help clinicians adjust their biopsy timetable and/or assessment of PC risk in
      ASAP-diagnosed patients with a PSA level of 4-10 ng/mL.

PMID- 30294802
TI  - Collagenous and elastotic marginal plaques of the hand: A potential clue to the
      diagnosis of alkaptonuria.
AB  - Collagenous and elastotic marginal plaques of the hand (CEMPH) is a rare, chronic
      keratoderma characterized by hyperkeratotic linear plaques located along the
      radial and ulnar aspects of the hands bilaterally. As an isolated finding, CEMPH
      occurs secondarily to chronic trauma and photodamage. Herein, CEMPH is described
      as a manifestation of alkaptonuria (AKU). In addition to keloidal collagen,
      ochronotic fibers and fragmented, thickened elastic fibers were observed.
      Additionally, mucin deposition-not previously described in this clinical context
      was also identified. Given their overlapping clinicopathologic features, CEMPH
      due to AKU should be distinguished from the acquired variant as well as
      acrokeratoelastoidosis.

PMID- 30294804
TI  - Coevolution of Lexical Meaning and Pragmatic Use.
AB  - According to standard linguistic theory, the meaning of an utterance is the
      product of conventional semantic meaning and general pragmatic rules on language
      use. We investigate how such a division of labor between semantics and pragmatics
      could evolve under general processes of selection and learning. We present a game
      theoretic model of the competition between types of language users, each endowed
      with certain lexical representations and a particular pragmatic disposition to
      act on them. Our model traces two evolutionary forces and their interaction: (i)
      pressure toward communicative efficiency and (ii) transmission perturbations
      during the acquisition of linguistic knowledge. We illustrate the model based on
      a case study on scalar implicatures, which suggests that the relationship between
      underspecified semantics and pragmatic inference is one of coevolution.

PMID- 30294803
TI  - Assessment of eosinophils in gastrointestinal inflammatory disease of dogs.
AB  - BACKGROUND: Accurate identification of eosinophils in the gastrointestinal (GI)
      tract of dogs with eosinophilic GI disease (EGID) by histological evaluation is
      challenging. The currently used hematoxylin and eosin (H&E) staining method
      detects intact eosinophils but does not detect degranulated eosinophils, thus
      potentially underrepresenting the number of infiltrating eosinophils. OBJECTIVE:
      To develop a more sensitive method for identifying and quantifying both intact
      and degranulated eosinophils to diagnose EGID more accurately. METHODS:
      Endoscopically obtained paraffin-embedded intestinal biopsy specimens from dogs
      with GI signs were examined. The study groups were dogs with eosinophilic
      enteritis (EE), lymphoplasmacytic and mixed enteritis, and control dogs with GI
      signs but no histologic changes on tissue sections. Consecutive sections were
      immunolabeled with monoclonal antibodies (mAbs) against the eosinophil granule
      protein eosinophil peroxidase (Epx) and stained by H&E, respectively. The number
      of eosinophils was manually quantified and classified as intact or degranulated.
      RESULTS: The number of intact eosinophils detected in Epx mAb-labeled duodenal
      sections was significantly higher compared with that in H&E-stained sections,
      with a similar relationship noted in the colon and stomach. The Epx mAb allowed
      the unique assessment of eosinophil degranulation. The number of intact and
      degranulated eosinophils was significantly higher in duodenal lamina propria of
      the EE and mixed group compared to the control group. CONCLUSION:
      Immunohistochemical detection of Epx provides a more precise method to detect GI
      tract eosinophils compared to H&E staining and could be used as an alternative
      and reliable diagnostic tool for assessment of biopsy tissues from dogs with
      EGID.

PMID- 30294805
TI  - GRAND CHALLENGES IN ASSESSING THE ADVERSE EFFECTS OF CONTAMINANTS OF EMERGING
      CONCERN ON AQUATIC FOOD WEBS.
AB  - Much progress has been made in the past decades to understand the sources,
      transport, fate and biological effects of contaminants of emerging concern (CECs)
      in aquatic ecosystems. Despite these advancements, significant obstacles remain
      to comprehensively assess the environmental risks associated with the presence of
      CECs. Many of these obstacles center around the extrapolation of effects of
      single chemicals observed in the laboratory or effects observed in individual
      organisms or species in the field to impacts of multiple stressors on aquatic
      food webs. In the current review, we identified five challenges that need to be
      addressed to advance studies of CECs from singular exposure events to multi
      species aquatic food web interactions: (i) more detailed information on the
      complexity of mixtures of CECs in the aquatic environment; (ii) understanding sub
      lethal effects of CECs on a wide range of aquatic organisms; (iii) ascertaining
      the biological consequences of variable duration CEC exposures within and across
      generations in aquatic species; (iv) linkage of multiple stressors with CEC
      exposure in aquatic systems; and (v) documenting the trophic consequences of CEC
      exposure across aquatic food webs. We review the current literature to
      demonstrate how these challenges can be addressed to fill knowledge gaps. This
      article is protected by copyright. All rights reserved.

PMID- 30294806
TI  - Event Structures Drive Semantic Structural Priming, Not Thematic Roles: Evidence
      From Idioms and Light Verbs.
AB  - What are the semantic representations that underlie language production? We use
      structural priming to distinguish between two competing theories. Thematic roles
      define semantic structure in terms of atomic units that specify event
      participants and are ordered with respect to each other through a hierarchy of
      roles. Event structures instead instantiate semantic structure as embedded sub
      predicates that impose an order on verbal arguments based on their relative
      positioning in these embeddings. Across two experiments, we found that priming
      for datives depended on the degree of overlap in event structures. Specifically,
      while all dative structures showed priming, due to common syntax, there was a
      boost for compositional datives priming other compositional datives. Here, the
      two syntactic forms have distinct event structures. In contrast, there was no
      boost in priming for dative light verbs, where the two forms map onto a single
      event representation. On the thematic roles hypothesis, we would have expected a
      similar degree of priming for the two cases. Thus, our results support event
      structural approaches to semantic representation and not thematic roles.

PMID- 30294807
TI  - Risk assessment communication difficulties: An empirical examination of the
      effects of categorical versus probabilistic risk communication in sexually
      violent predator decisions.
AB  - Expert testimony concerning risk and its communication to the trier of fact has
      important implications for some of the most significant legal decisions. In a
      simulated sexual violent predator hearing, we examined how mock jurors interpret
      and use recidivism risk expert testimony communicated either categorically, using
      verbal labels, or probabilistically, using numeric values. Based upon the STATIC
      99R, we compared mock jurors' decision-making and verdicts when we manipulated
      the style of risk communication across four different risk levels. In terms of
      verdict decisions, we found that higher risk levels were associated with more
      commitment decisions, but that this relationship only existed for the categorical
      risk-communication format. We also replicated previous research demonstrating
      that participants overestimate recidivism risk in general, especially when higher
      risk is communicated categorically. Finally, our participants did not
      differentiate well between the four levels of risk offered, instead apparently
      employing a more simplistic dichotomy between "low" or "high" risk for both their
      verdict decisions and their thresholds for commitment. The legal and policy
      implications of our findings are discussed, as well as suggestions for more
      effective presentation of expert risk testimony.

PMID- 30294808
TI  - Eye'll Help You Out! How the Gaze Cue Reduces the Cognitive Load Required for
      Reference Processing.
AB  - Referential gaze has been shown to benefit language processing in situated
      communication in terms of shifting visual attention and leading to shorter
      reaction times on subsequent tasks. The present study simultaneously assessed
      both visual attention and, importantly, the immediate cognitive load induced at
      different stages of sentence processing. We aimed to examine the dynamics of
      combining visual and linguistic information in creating anticipation for a
      specific object and the effect this has on language processing. We report
      evidence from three visual-world eye-tracking experiments, showing that
      referential gaze leads to a shift in visual attention toward the cued object,
      which consequently lowers the effort required for processing the linguistic
      reference. Importantly, perceiving and following the gaze cue did not prove
      costly in terms of cognitive effort, unless the cued object did not fit the verb
      selectional preferences.

PMID- 30294809
TI  - Malnutrition Risk in Hospitalized Children: A Descriptive Study of Malnutrition
      Related Characteristics and Development of a Pilot Pediatric Risk-Assessment
      Tool.
AB  - BACKGROUND: Underrecognition of pediatric malnutrition may affect nutrition
      interventions and outcomes. Pediatric malnutrition uses more specific etiology
      based criteria but lacks clarity in implementation guidelines. Study goals were
      to identify malnutrition and risk among hospitalized patients, characterize
      malnutrition risk factors, and assess reliability of criteria against outcome
      measures. MATERIALS AND METHODS: All children 44 weeks postmenstrual age-18
      years, admitted for 48 hours during a 16-day period, were included (n = 528).
      Trained dietitians assessed patients in physical assessments (PA), growth, energy
      intake, increased nutrient losses (IL), altered absorption of nutrients (AA),
      hypermetabolism and inflammation, laboratory information, micronutrient
      deficiency, and functional status. Outcome data assessed were length of stay
      (LOS), intensive care unit (ICU) LOS, ventilation days, nutrition support, and
      dietitian intervention. RESULTS: Malnutrition prevalence upon admission was
      19.7%. Weight/length or BMI/age z-score (ZS) had no effect on LOS. AA and IL upon
      admission were independently associated with malnutrition (both, P<.01). Wasting
      and hypermetabolism were independently associated with longer LOS (P<.01). Other
      factors associated with longer LOS included IL and inflammation (P < .05). Those
      with hypermetabolism had significant ZS improvements if followed by a dietitian
      (P < .05). Wasting via PA was the only factor associated with longer ICU LOS (P <
      .05). CONCLUSIONS: Identification of risk factors (wasting, hypermetabolism, AA,
      IL) beyond anthropometrics to define malnutrition and risk is important in
      prioritizing care in a tertiary pediatric facility. Of great significance is the
      ability of dietitian-based PA to predict LOS and need for intervention.

PMID- 30294810
TI  - Word Forms Are Structured for Efficient Use.
AB  - Zipf famously stated that, if natural language lexicons are structured for
      efficient communication, the words that are used the most frequently should
      require the least effort. This observation explains the famous finding that the
      most frequent words in a language tend to be short. A related prediction is that,
      even within words of the same length, the most frequent word forms should be the
      ones that are easiest to produce and understand. Using orthographics as a proxy
      for phonetics, we test this hypothesis using corpora of 96 languages from
      Wikipedia. We find that, across a variety of languages and language families and
      controlling for length, the most frequent forms in a language tend to be more
      orthographically well-formed and have more orthographic neighbors than less
      frequent forms. We interpret this result as evidence that lexicons are structured
      by language usage pressures to facilitate efficient communication.

PMID- 30294811
TI  - Novel MBTPS2 mutation causes a mild phenotype of ichthyosis follicularis with
      atrichia and photophobia syndrome in a Chinese pedigree.

PMID- 30294812
TI  - Programmable Coding Acoustic Topological Insulator.
AB  - Topological acoustics has recently revolutionized fundamental concepts of
      acoustic propagation, giving rise to strikingly unique acoustic edge modes immune
      to backscattering. Despite the rapid progress in this field, simultaneous
      realization of reconfigurability, intelligentization, and automatic control over
      acoustic propagation paths is posing a great challenge. This challenge is
      overcome by proposing the concept of a programmable acoustic topological
      insulator based on two digital elements "0" or "1," which consist of honeycomb
      lattice sonic crystals made of cylindrical rods with different diameters. The
      acoustic propagation paths in the topological insulators can be controlled
      automatically by programming different coding sequences, which arises from
      efficient transformation of pseudospin-dependent edge modes on both interfaces of
      the digital elements. More importantly, a unique unit is experimentally
      fabricated that has either a "0" or "1" response automatically manipulated by an
      air cylinder, and design topological insulators with programmable functionality,
      to realize three digital acoustic devices, such as a single-pole double-throw
      switch, a single-pole single-throw switch, and a tunable logic gate. The proposed
      programmable topological insulators may enable future intelligent acoustic
      devices with exciting reconfigurable and programmable functionalities, which may
      lead to important advances in various applications, such as integrated acoustics,
      acoustic security, and information processing.

PMID- 30294813
TI  - Practical tools and strategies for researchers to increase replicability.
AB  - A growing body of evidence indicates that the effects reported in many scientific
      fields may be overestimated or even false. This problem has gained a lot of
      attention in the field of psychology, where researchers have even started to
      speak of a 'replication crisis'. Fortunately, a number of measures to rectify
      this problem have already been proposed and implemented, some inspired by
      practices in other scientific fields. In this review, I briefly examine this
      issue in the field of psychology and suggest some practical tools and strategies
      that researchers can implement to increase replicability and the overall quality
      of their scientific research. WHAT THIS PAPER ADDS: Researchers can implement
      many practical tools and strategies to improve replicability of their findings.
      Strategies include improving statistical inference, pre-registration, multisite
      collaboration, and sharing data. Different scientific fields could benefit from
      looking at each other's best practices.

PMID- 30294814
TI  - Exploring Self-Healing Liquid Na-K Alloy for Dendrite-Free Electrochemical Energy
      Storage.
AB  - The development of high-performance dendrite-free liquid-metal anodes at room
      temperature is of great importance for the advancement of alkali metal batteries.
      Herein an intriguing self-healing liquid dendrite-free Na-K alloy, fabricated by
      a facile room-temperature alloying process, aiming for application in potassium
      ion batteries is reported. Through extensive investigation, its self-healing
      characteristics are rooted upon a thin solid K2 O layer (KOL) coated on the
      liquid Na-K alloy. The KOL not only acts as a protective layer to prevent the Na
      K alloy from making contact with the electrolyte, but also greatly improves the
      wetting capability and adhesion between the liquid alloy and the carbon matrix
      (e.g., carbon fiber cloth (CFC)) to form a stable interface. Consequently, the as
      prepared CFC/KOL@Na-K alloy anode exhibits prominent electrochemical performance
      with smaller hysteresis (less than 0.3 V beyond 140 cycles at 0.4 mA cm-2 ),
      better capacity retention, and higher Coulombic efficiency than the CFC/bare Na-K
      alloy counterpart. When coupled with a potassium Prussian blue (PPB) cathode, the
      full cell manifests higher capability retention and improved cycling stability.
      This research deepens the understanding of self-healing Na-K alloys and opens a
      new way to achieve high-performance dendrite-free alkali metal anodes for
      application in rechargeable batteries.

PMID- 30294815
TI  - Effects of capsaicin application on the skin during resting exposure to temperate
      and warm conditions.
AB  - We investigated thermoregulatory and cardiovascular responses at rest in a
      temperate (20 degrees C) and in a warm (30 degrees C) environment (40% RH)
      without and with the application of capsaicin on the skin. We hypothesized that
      regardless of environmental temperature, capsaicin application would stimulate
      heat loss and concomitantly deactivate heat conservation mechanisms, thus
      resulting in rectal temperature (Tre) and mean blood pressure decline due to
      excitation of heat-sensitive TRPV1. Ten male subjects were exposed, while seated,
      for 30 minutes to 20.8 +/- 1.0 degrees C or to 30.6 +/- 1.1 degrees C: without
      (NCA) and with (CA) application of capsaicin patches on the skin.
      Thermoregulatory (Tre, proximal-distal skin temperature gradient) and
      cardiovascular variables (modelflow technique) as well as oxygen uptake were
      continuously measured. The area under the curve for Tre decline at 20 degrees C
      was smaller in CA (-2.1 +/- 1.3 a.u.) than in NCA (-0.6 +/- 1.1 a.u., P < 0.01, r
      = 0.8). Likewise, at 30 degrees C it was smaller in CA (-2.2 +/- 2.1 a.u.)
      compared to NCA (-0.8 +/- 2.0 a.u., P = 0.02, r = 0.7). Local vasomotor tone and
      oxygen uptake, were significantly lower by 36.7% +/- 94.2% and 12.3% +/- 12.3%,
      respectively, with capsaicin compared to NCA (P = 0.05 and P < 0.01,
      respectively). Additionally, in 30 degrees C CA mean arterial pressure was lower
      by 10.7% +/- 5.9%, 8.9% +/- 5.9%, and 10.6% +/- 7.0% compared to 30 degrees C
      NCA, 20 degrees C NCA, and 20 degrees C CA, respectively (P < 0.01, P = 0.02, and
      P < 0.01, respectively, d = 1.4-1.8). In conclusion, capsaicin application on the
      skin induced vasodilation and Tre decline. At 30 degrees C CA, thermal responses
      were accompanied by arterial hypotension most likely due to the interactive
      effects of both stressors (warm environment and capsaicin) on cutaneous vascular
      regulation.

PMID- 30294816
TI  - Weight loss and breast cancer incidence in postmenopausal women.
AB  - BACKGROUND: Although obesity is an established risk factor for postmenopausal
      breast cancer, the results of weight loss and breast cancer studies are
      inconsistent. Therefore, we evaluated associations between weight change and
      breast cancer risk in postmenopausal women in the Women's Health Initiative
      Observational Study. METHODS: Postmenopausal women (n = 61,335) who had no prior
      breast cancer and a normal mammogram had body weight and height measured and body
      mass index (BMI) calculated at baseline and year 3. Weight change at year 3 was
      categorized as stable (<5%), loss (>=5%), or gain (>=5%) with further assessment
      of weight loss intentionality by self-report. Multivariable Cox proportional
      hazard regression models were used to evaluate relationships between weight
      change and subsequent breast cancer incidence. RESULTS: During a mean follow-up
      of 11.4 years with 3061 incident breast cancers, women with weight loss (n =
      8175) had a significantly lower risk of breast cancer compared with women whose
      weight remained stable (n = 41,139) (hazard ratio [HR], 0.88; 95% confidence
      interval [CI], 0.78-0.98; P = .02) with no interaction by BMI. Adjustment for
      mammography did not alter findings (HR, 0.88; 95% CI, 0.78-0.99) with no
      significant difference by weight loss intentionality. Weight gain (>=5%) (n =
      12,021) was not associated with breast cancer risk (HR, 1.02; 95% CI, 0.93-1.11)
      but was associated with higher triple-negative breast cancer incidence (HR, 1.54;
      95% CI, 1.16-2.05). CONCLUSIONS: Postmenopausal women who lose weight have lower
      breast cancer risk than those with stable weight. These findings suggest that
      postmenopausal women who lose weight may reduce their breast cancer risk.

PMID- 30294818
TI  - The advantages of proteomic investigation in the management of male accessory
      gland infection: A response to Grande et al.

PMID- 30294819
TI  - Histology and ultrastructure of hepatic nodular alterations in Clarias gariepinus
      (Burchell, 1822).
AB  - This study aimed to assess the macroscopic appearance, histology and
      ultrastructure of liver nodular alterations in sharptooth catfish Clarias
      gariepinus (Burchell, 1822) from a hyper-eutrophic freshwater impoundment. The
      livers of 25 fish were sampled for microscopy analyses, otoliths were collected
      for age estimation, and the hepatosomatic index (HSI) was calculated. The light
      microscopic analysis of the nodular tissue revealed hepatocellular and nuclear
      pleomorphism, pyknotic nuclei, variation in cytoplasmic appearance and focal
      areas of cellular alterations (FCAs). An increase in the size and number of
      melano-macrophage centres, intracellular deposits, steatosis and giant cells was
      also identified. The ultrastructural alterations identified included cell
      membrane disruption, irregular shaped nuclei with augmentation of the nucleolus
      and deformed nuclear envelopes. In addition, we found dilation, proliferation,
      fragmentation and vesiculation of the cisternae of the rough endoplasmic
      reticulum (RER). Furthermore, there was an increase in degenerative mitochondria
      (transparent matrix), swelling of mitochondria and proliferation of both
      peroxisomes and lysosomes. The histological and ultrastructural alterations
      identified did not explain the variation in macroscopic colour of the nodules. We
      did not find a strong positive correlation between age and HSI; however, the
      oldest fish (18 years) did present the most nodules.

PMID- 30294817
TI  - Diboron-Assisted Interfacial Defect Control Strategy for Highly Efficient Planar
      Perovskite Solar Cells.
AB  - Metal halide perovskite films are endowed with the nature of ions and
      polycrystallinity. Formamidinium iodide (FAI)-based perovskite films, which
      include large cations (FA) incorporated into the crystal lattice, are most likely
      to induce local defects due to the presence of the unreacted FAI species. Here, a
      diboron-assisted strategy is demonstrated to control the defects induced by the
      unreacted FAI both inside the grain boundaries and at the surface regions. The
      diboron compound (C12 H10 B2 O4 ) can selectively react with unreacted FAI,
      leading to reduced defect densities. Nonradiative recombination between a
      perovskite film and a hole-extraction layer is mitigated considerably after the
      introduction of the proposed approach and charge-carrier extraction is improved
      as well. A champion power conversion efficiency of 21.11% is therefore obtained
      with a stabilized power output of 20.83% at the maximum power point for planar
      perovskite solar cells. The optimized device also delivers negligible hysteresis
      effect under various scanning conditions. This approach paves a new way for
      mitigating defects and improving device performance.

PMID- 30294820
TI  - Versatility in the Brook Rearrangement for the Selective Ring-Opening of Three
      Membered Rings.
AB  - From a single alpha-silylated carbinol intermediate, easily accessible by
      carbometallation of cyclopropenes, various scaffolds featuring a quaternary
      carbon stereocenter could be obtained selectively. The selectivity towards these
      different products was achieved by either changing the experimental conditions or
      the nature of the organometallic species involved.

PMID- 30294821
TI  - The polarity effect of compact ionization chambers used for small field
      dosimetry.
AB  - PURPOSE: The recent developments of compact air-filled ionization chambers for
      use in small photon beams have raised the needs to address the associated
      polarity effect. The polarity effect of five compact ionization chambers has been
      quantified at small field sizes. The origins of the polarity effect are studied
      experimentally and through Monte-Carlo simulations. For this purpose, the one
      dimensional lateral dose-response functions were determined using positive and
      negative chamber's polarity. Monte-Carlo simulations were performed to study the
      underlying mechanism of the polarity effect by quantifying the charge imbalance
      in the collecting electrode and cable. METHODS: Five novel compact ionization
      chamber designs have been studied (PTW-Freiburg: Semiflex 3D 31021, PinPoint 3D
      31022 and PinPoint 31023; IBA Dosimetry: Razor chamber CC01-G and Razor Nano
      chamber CC003). Output ratios were measured down to a nominal field side length
      of 3 mm using both polarities to evaluate the polarity effect at different field
      sizes. The small field output correction factors were derived using a
      scintillator detector as reference. To identify the origins of the polarity
      effect, slit beam measurements were performed to obtain their lateral dose
      response functions. All measurements were performed using three chamber
      orientations: axial, radial crossplane, and radial inplane. The chambers were
      modeled according to the manufacturers' blueprints using the Monte-Carlo package
      EGSnrc. The charge imbalance due to electrons entering and leaving the inner
      electrode and cable was studied using an adapted user-code. RESULTS: The output
      ratios obtained using all five chambers show field size-dependent polarity
      effects at small field sizes in the axial orientation, whereas no significant
      field size dependence of the polarity effect has been observed in the radial
      orientations. The chambers' lateral dose-response functions reveal that the
      radiation-induced charge imbalance in the inner electrode and cable is the main
      cause of the observed polarity effect at small field sizes. The effect is weakest
      for the largest PTW 31021 chamber but intensifies for smaller chambers with
      decreasing sensitive air volume. Consistent results have been obtained between
      Monte-Carlo simulations and measurement data. CONCLUSIONS: Awareness needs to be
      raised so that the polarity effect of novel compact ionization chambers is
      appropriately accounted for in small field dosimetry. The results in this work
      are useful to identify the magnitude of the polarity effect correction and to
      assist in the decisions on choosing the appropriate chambers and setups during
      measurements. The origins of the observed polarity effect have been elucidated
      using the chambers' lateral dose-response functions. The adapted Monte-Carlo user
      code has been used to compute the radiation-induced charge imbalance in the
      chamber's components. It opens the possibility to study the chamber's design with
      the aim to minimize its polarity effect. Small field output correction factors
      computed according to TRS 483 have been reported for these investigated chambers.

PMID- 30294822
TI  - Factors influencing nursing home placement of patients with dementia: a
      retrospective, single-centre study in Japan.
AB  - AIM: This was an exploratory study to examine the factors influencing nursing
      home placement (NHP) in Japan. METHODS: For this analysis, 633 patients were
      selected. The data were collected from the clinical records of each patient. A
      log-rank test was performed. The time from the patient's first visit to the
      clinic until the nursing home placement was the independent variable. Age (<80 or
      >=80 years), biological sex (male or female), Clinical Dementia Rating scale
      (CDR) score (overall index 0.5, 1, 2, or 3), living situation (living alone or
      with someone), and voxel-based specific regional analysis systems for Alzheimer's
      disease Z-score (<2 or >=2) were the dependent variables. Survival curves were
      obtained by using the Kaplan-Meier estimate. After the log-rank test, we
      conducted a Cox proportional hazards regression analysis. RESULTS: The results of
      log-rank test indicated that all the variables could significantly influence time
      to NHP. Cox proportional hazards regression analysis suggested that CDR 3
      exhibited the highest hazard ratio and Z-score showed the lowest hazard ratio.
      There were significant differences in age, sex, CDR 2, CDR 3, and living
      situation. CONCLUSIONS: The results indicated that the voxel-based specific
      regional analysis systems for Alzheimer's disease Z-score is unlikely to
      influence NHP. This may suggest that even if the atrophy in the medial temporal
      lobe is rather progressed, patients can remain living at their own home with
      protective factors. Future studies need to investigate the risk and protective
      factors of time to NHP by combining the variables.

PMID- 30294823
TI  - Cluster analysis with MOODS-SR illustrates a potential bipolar disorder risk
      phenotype in young adults with remitted major depressive disorder.
AB  - OBJECTIVES: Delays in the diagnosis and detection of bipolar disorder can lead to
      adverse consequences, including improper treatment and increased suicide risk.
      The Mood Spectrum Self-Report Measure (MOODS-SR) was designed to capture the full
      spectrum of lifetime mood symptomology with factor scores for depression and
      mania symptom constellations. The utility of the MOODS-SR as a tool to
      investigate homogeneous subgroups was examined, with particular focus on a
      possible bipolar risk subgroup. Moreover, potential patterns of differences in
      MOODS-SR subtypes were probed using cognitive vulnerabilities, neuropsychological
      functioning, and ventral striatum connectivity. METHODS: K-mean cluster analysis
      based on factor scores of MOODS-SR was used to determine homogeneous subgroupings
      within a healthy and remitted depressed young adult sample (N = 86). Between
      group comparisons (based on cluster subgroupings) were conducted on measures of
      cognitive vulnerabilities, neuropsychological functioning, and ventral striatum
      rs-fMRI connectivity. RESULTS: Three groups of participants were identified: one
      with minimal symptomology, one with moderate primarily depressive symptomology,
      and one with more severe manic and depressive symptomology. Differences in
      impulsivity, neuroticism, conscientiousness, facial perception accuracy, and rs
      fMRI connectivity exist between moderate and severe groups. CONCLUSIONS: Within a
      sample of people with and without depression histories, a severe subgroup was
      identified with potentially increased risk of developing bipolar disorder through
      use of the MOODS-SR. This small subgroup had higher levels of lifetime depression
      and mania symptoms. Additionally, differences in traits, affective processing,
      and connectivity exist between those with a more prototypic unipolar subgrouping
      and those with potential risk for developing bipolar disorder.

PMID- 30294824
TI  - Responding to natural disasters: Examining identity and prosociality in the
      context of a major earthquake.
AB  - How does a major natural disaster relate to individuals' orientation towards
      society? We collected repeated cross-sectional surveys before (n = 644) and after
      the 2010 Chile earthquake (n = 1,389) to examine levels of national identity,
      prosocial values, helping motivations, and prosocial behaviours in the context of
      such a calamitous societal event. Our research questions, derived from the
      literature on helping in times of crisis, considered how natural disasters may
      implicate identity and prosociality, as well as how identity, prosocial values,
      and motivations are linked to prosocial action after a disaster. Higher levels of
      national identity, helping motivations, and disaster-related helping were found
      after the earthquake, suggesting that in the aftermath of a disaster, people
      unite under a common national identity and are motivated to take action related
      to disaster relief. National identity and prosocial values were closely linked to
      helping after the earthquake, but specific helping motivations rarely predicted
      prosocial behaviours. Additionally, proximity to the epicentre was related to
      higher levels of national identity and participation in reconstruction efforts.
      These findings contribute to our understanding of people's responses to natural
      disasters and suggest ways of encouraging prosocial behaviour in the aftermath of
      unexpected tragic events.

PMID- 30294825
TI  - Cardiac effects of 6 months' dietary nitrate and spironolactone in patients with
      hypertension and with/at risk of type 2 diabetes, in the factorial design, double
      blind, randomized controlled VaSera trial.
AB  - AIMS: The aims of the present study were to explore whether a long-term
      intervention with dietary nitrate [(NO3 - ), a potential tolerance-free source of
      beneficial vasoactive nitric oxide] and spironolactone (to oppose aldosterone's
      potential deleterious cardiovascular effects) improve cardiac structure/function,
      independently of blood pressure (BP), in patients with/at risk of type 2 diabetes
      (a population at risk of heart failure). METHODS: A subsample of participants in
      our double-blind, randomized, factorial-design intervention (VaSera) trial of
      active beetroot juice as a nitrate source (<=11.2 mmol) or placebo (nitrate
      depleted) beetroot juice, and either <=50 mg spironolactone or <=16 mg doxazosin
      (control), had transthoracic cardiac ultrasounds at baseline (n = 105), and at 3
      months and 6 months (n = 87) after the start of the intervention. Analysis was by
      modified intent-to-treat. RESULTS: Nitrate-containing juice (n = 40) decreased
      left ventricular (LV) end-diastolic volume {-6.3 [95% confidence interval (CI) 
      11.1, -1.6] ml} and end-systolic volume [-3.2 (95% CI -5.9, -0.5) ml], and
      increased end-diastolic mass/volume ratio [+0.04 (95% CI 0.00, 0.07)], relative
      to placebo juice (n = 47). Spironolactone (n = 44) reduced relative wall
      thickness compared with doxazosin (n = 43) [-0.01 (95% CI -0.02, -0.00)].
      Although spironolactone reduced LV mass index relative to baseline [-1.48 (95% CI
      -2.08, -0.88) g m-2.7 ], there was no difference vs. doxazosin [-0.85 (95% CI 
      1.76, 0.05) g m-2.7 ]. Spironolactone also decreased the E/A ratio [-0.12 (95% CI
      -0.19, -0.04)] and increased S' (a tissue-Doppler systolic function index) by
      0.52 (95% CI 0.05, 1.0) cm s-1 . BP did not differ between the juices, or between
      the drugs. CONCLUSIONS: Six months' dietary nitrate decreased LV volumes ~5%,
      representing new, sustained, BP-independent benefits on cardiac structure,
      extending mechanisms characterized in preclinical models of heart failure.
      Spironolactone's effects on cardiac remodelling and systolic-diastolic function,
      although confirmatory, were independent of BP.

PMID- 30294826
TI  - Improving the oral health of older people in hospital.
AB  - OBJECTIVE: To determine whether an oral health therapist daily oral hygiene
      intervention, compared with the same routine performed by nurses with some dental
      support, can improve the oral health of older inpatients. METHODS: A prospective
      study was conducted at two tertiary referral hospitals with three phases: (i) pre
      intervention (PI) usual oral care; (ii) oral health therapist intervention
      (OHTI); and (iii) nurse-led intervention (NI). Oral health was assessed with the
      Oral Health Assessment Tool. RESULTS: Three hundred and fifty nine patients
      participated across three phases (PI (n = 206); OHTI (n = 77); NI (n = 76)). In
      the intervention groups, there was a significant decrease in 'unhealthy' oral
      cleanliness at day 7, OHTI; 86 to 53% (P < 0.001), NI; 80 to 50% (P < 0.001)
      compared to PI; 78 to 72% (P > 0.14). Movement from 'unhealthy' oral cleanliness
      at day 1 to 'healthy' at day 7 was significantly higher in the OHTI (35%) and NI
      (37%) compared to PI (17%) (P < 0.001). CONCLUSION: With support, nurses can
      improve the oral health of older patients similarly to an oral health therapist.

PMID- 30294827
TI  - Primary tumor resection in metastatic breast cancer: A propensity-matched
      analysis, 1988-2011 SEER data base.

PMID- 30294828
TI  - Effect of methotrexate monotherapy on T-cell subsets in the peripheral
      circulation in psoriasis.
AB  - BACKGROUND: Psoriasis is a T-helper (Th)1/Th17-mediated chronic inflammatory
      disease. There is an increased population of Th cells in skin lesions and
      peripheral circulation of patients with psoriasis. Systemic methotrexate (MTX) is
      an effective treatment for moderate to severe psoriasis; however, its effect on
      different T-cell subsets is not yet clear. AIM: To study the effect of MTX
      monotherapy on the psoriatic T-cell profile in the peripheral circulation of
      patients with psoriasis. METHODS: This was a follow-up study involving 50
      patients with moderate to severe psoriasis treated with systemic MTX for 12
      weeks. Blood samples (5 mL) were collected from participants, from which PBMCs
      were isolated, and T-cell phenotyping was performed by flow cytometry. RESULTS:
      Following 12 weeks of MTX treatment, there was an increase in the percentages of
      Th2/Treg cells, and a relative decrease in the percentages of Th1/Th17 cells,
      along with a significant reduction in the median Psoriasis Area and Severity
      Index (PASI). CONCLUSION: MTX helps in the restoration of the immune balance by
      decreasing the numbers of Th1 and Th17 cells and increasing the numbers of Th2
      and Treg cells, thus resulting in a significant reduction in disease severity.
      MTX converts a proinflammatory T-cell phenotype to a protective anti-inflammatory
      phenotype, thus significantly suppressing the inflammation in psoriasis.

PMID- 30294829
TI  - Network-based integration of mRNA and miRNA profiles reveals new target genes
      involved in pancreatic cancer.
AB  - Pancreatic cancer is regarded as the most fatal and aggressive malignancy cancer
      due to its low 5-year survival rate and poor prognosis. The approaches of early
      diagnosis and treatment are limited, which makes it urgent to identify the
      complex mechanism of pancreatic oncogenesis. In this study, we used RNA-seq to
      investigate the transcriptomic (mRNA and miRNA) profiles of pancreatic cancer in
      paired tumor and normal pancreatic samples from ten patients. More than 1000
      differentially expressed genes were identified, nearly half of which were also
      found to be differentially expressed in the majority of examined patients.
      Functional enrichment analysis revealed that these genes were significantly
      enriched in multicellular organismal and metabolic process, secretion, mineral
      transport, and intercellular communication. In addition, only 24 differentially
      expressed miRNAs were found, all of which have been reported to be associated
      with pancreatic cancer. Furthermore, an integrated miRNA-mRNA interaction network
      was generated using multiple resources. Based on the calculation of disease
      correlation scores developed here, several genes present in the largest connected
      subnetwork, such as albumin, ATPase H+ /K+ exchanging alpha polypeptide and
      carcinoembryonic antigen-related cell adhesion molecule 1, were considered as
      novel genes that play important roles in the development of pancreatic cancer.
      Overall, our data provide new insights into further understanding of key
      molecular mechanisms underlying pancreatic tumorigenesis.

PMID- 30294830
TI  - The benefits of integrating dental and dental therapy and hygiene students in
      undergraduate curricula.
AB  - PURPOSE: The purpose of the current study was to evaluate the impact of
      integrating the teaching of Bachelor of Dental Surgery (BDS) and Bachelor of
      Dental Therapy and Hygiene (BScDTH) students in enquiry-based learning (EBL)
      sessions, using performance on multiple related integrated dental science (IDS)
      multiple-choice question assessments. METHOD: IDS assessments are sat twice in
      the first stages of both the BDS and BScDTH programmes. IDS scores from
      integrated and non-integrated cohorts were collated and compared across test
      occasions (first or second assessment of the stage) and programmes (BDS and
      BScDTH). RESULTS: The results revealed that IDS scores were, overall,
      significantly higher for students in integrated (M = 63.46, SD = 13.06) than non
      integrated EBL groups (M = 60.75, SD = 13.67; F(1,207) = 4.277, P = 0.040, 
      CONCLUSIONS: Integrating students from different programmes for the teaching of
      core dental knowledge in team environments improves student performance in
      subsequent dental science assessments-and more so for BScDTH than BDS students.
      The fact that both groups benefit from integration should go some way towards
      reassuring institutions that are considering integration but are cautious of
      threats to "established" programmes.

PMID- 30294831
TI  - Detection of MAPK/ERK pathway proteins and KRAS mutations in adenomatoid
      odontogenic tumors.
AB  - OBJECTIVE: This study aimed to assess the frequency of KRAS mutation and its
      association with the presence of the MAPK/ERK signaling pathway proteins in
      adenomatoid odontogenic tumors. STUDY DESIGN: Paraffin-embedded tissue samples
      from nine cases of adenomatoid odontogenic tumor were used. Genomic DNA was
      extracted from each sample; in one case, genetic mutations in 50 cancer
      associated genes were examined by next-generation sequencing. Hotspot mutations
      in the RAS family were analyzed by Luminex assay using the remaining eight cases.
      Subsequently, immunohistochemistry for KRAS, CRAF, BRAF, EGFR, ERK, MEK, and
      BRAFV600E was performed. RESULTS: A KRAS G12D missense mutation was detected in
      the DNA sequence of the tumor cells, but it was not detected in the stromal
      tissue. KRAS G12V and KRAS G12R mutations were detected in two and four cases,
      respectively. For immunohistochemistry, all the cases were EGFR, KRAS, BRAF, CRAF
      positive, one case was ERK negative,and one case was MEK and ERK negative, all
      the other remaining cases were MEK and ERK positive. CONCLUSION: KRAS mutation at
      codon 12 and the presence of MAPK/ERK pathway proteins were detected suggesting
      their association with tumorigenesis of adenomatoid odontogenic tumors.

PMID- 30294832
TI  - Bullous pyoderma gangrenosum secondary to underlying multiple myeloma: treated
      with ciclosporin.

PMID- 30294834
TI  - Could we do more?

PMID- 30294833
TI  - ACVECC-Veterinary Committee on Trauma Registry Report 2013-2017.
AB  - OBJECTIVE: To report summative data from the American College of Veterinary
      Emergency and Critical Care Veterinary Committee on Trauma (VetCOT) registry.
      DESIGN: Multi-institutional veterinary trauma registry data report. SETTING:
      VetCOT identified veterinary trauma centers (VTCs). ANIMALS: Dogs and cats with
      evidence of trauma presented to VTCs with data entered in the VetCOT registry
      September 1, 2013-March 31, 2017. INTERVENTIONS: VetCOT created a standardized
      data collection methodology for dog and cat trauma. Data were input to a web
      based data capture system (REDCap) by data entry personnel trained in data
      software use and operational definitions of data variables. Data on demographics,
      trauma type (blunt vs penetrating), preadmission care, hospitalization and
      intensive care requirement, trauma severity assessment at presentation (eg,
      modified Glasgow coma scale and animal trauma triage score), key laboratory
      parameters, necessity for surgical intervention, and case outcome were collected.
      Summary descriptive data for each species are reported. MEASUREMENTS AND MAIN
      RESULTS: Twenty-nine VTCs in North America, Europe, and Australia contributed
      information from 17,335 dog and 3,425 cat trauma cases during the 42-month
      reporting period. A large majority of cases presented directly to the VTC after
      injury (80.4% dogs and 78.1% cats). Blunt trauma was the most common source for
      injury in cats (56.7%); penetrating trauma was the most common source for injury
      in dogs (52.3%). Note that 43.8% of dogs and 36.2% of cats were reported to have
      surgery performed. The proportion surviving to discharge was 92.0% (dogs) and
      82.5% (cats). CONCLUSIONS: The VetCOT registry proved to be a powerful resource
      for collection of a large dataset on trauma in dogs and cats seen at VTCs. While
      overall survival to discharge was quite high, further evaluation of data on
      subsets of injury types, patient assessment parameters, interventions, and
      associated outcome are warranted.

PMID- 30294835
TI  - Pathophysiology and Treatment of Gastrointestinal Motility Disorders in the
      Acutely Ill.
AB  - Gastrointestinal dysmotility causes delayed gastric emptying, enteral feed
      intolerance, and functional obstruction of the small and large intestine, the
      latter functional obstructions being frequently termed ileus and Ogilvie
      syndrome, respectively. In addition to meticulous supportive care, drug therapy
      may be appropriate in certain situations. There is, however, considerable
      variation among individuals regarding what gastric residual volume identifies
      gastric dysmotility and would encourage use of a promotility drug. While the
      administration of either metoclopramide or erythromycin is supported by evidence
      it appears that, dual-drug therapy (erythromycin and metoclopramide) reduces the
      rate of treatment failure. There is a lack of evidence to guide drug therapy of
      ileus, but neither erythromycin nor metoclopramide appear to have a role. Several
      drugs, including ghrelin agonists, highly selective 5-hydroxytryptamine receptor
      agonists, and opiate antagonists are being studied in clinical trials.
      Neostigmine, when infused at a relatively slow rate in patients receiving
      continuous hemodynamic monitoring, may alleviate the need for endoscopic
      decompression in some patients.

PMID- 30294836
TI  - Community, Context, and Coping: How Social Connections Influence Coping and Well
      Being for Military Members and Their Spouses.
AB  - Military members and their spouses (n = 223 families) were selected from an
      Active Duty Army installation and assessed with regard to their connections with
      the military community, their levels of coping with military culture demands, and
      their reports of individual (depression and life satisfaction) and family well
      being. Guided by the contextual model of family stress and the social
      organization theory of action and change, results from a structural equation
      model indicated that military community connections, for both military members
      and their civilian spouses, were related to coping with the military culture and
      its demands, which in turn was related to both individual and family well-being.
      Unique actor and partner effects also emerged where both active duty military
      members' and their civilian spouses' perceptions of military community
      connections influenced the civilian spouses' satisfaction with military life, but
      only the active duty military members' community connections influenced their
      military-specific coping. Additionally, the associations between military
      specific coping and individual and family well-being only had actor effects. When
      examined within the context of important military culture elements, namely rank
      and extent of military transitions (deployment and relocation), these core
      findings linking communities to coping and well-being were unchanged.
      Implications for theory, future research, and practice are shared.

PMID- 30294837
TI  - Enzyme-mediated transglycosylation of rutinose (6-O-alpha-l-rhamnosyl-d-glucose)
      to phenolic compounds by a diglycosidase from Acremonium sp. DSM 24697.
AB  - The structure of the carbohydrate moiety of a natural phenolic glycoside can have
      a significant effect on the molecular interactions and physicochemical and
      pharmacokinetic properties of the entire compound, which may include anti
      inflammatory and anticancer activities. The enzyme 6-O-alpha-rhamnosyl-beta
      glucosidase (EC 3.2.1.168) has the capacity to transfer the rutinosyl moiety (6-O
      alpha-l-rhamnopyranosyl-beta-d-glucopyranose) from 7-O-rutinosylated flavonoids
      to hydroxylated organic compounds. This transglycosylation reaction was optimized
      using hydroquinone (HQ) and hesperidin as rutinose acceptor and donor,
      respectively. Since HQ undergoes oxidation in a neutral to alkaline aqueous
      environment, the transglycosylation process was carried out at pH values <=6.0.
      The structure of 4-hydroxyphenyl-beta-rutinoside was confirmed by NMR, that is, a
      single glycosylated product with a free hydroxyl group was formed. The highest
      yield of 4-hydroxyphenyl-beta-rutinoside (38%, regarding hesperidin) was achieved
      in a 2-h process at pH 5.0 and 30  degrees C, with 36 mM OH-acceptor and 5% (v/v)
      cosolvent. Under the same conditions, the enzyme synthesized glycoconjugates of
      various phenolic compounds (phloroglucinol, resorcinol, pyrogallol, catechol),
      with yields between 12% and 28% and an apparent direct linear relationship
      between the yield and the pKa value of the aglycon. This work is a contribution
      to the development of convenient and sustainable processes for the glycosylation
      of small phenolic compounds.

PMID- 30294839
TI  - A profile of the language and cognitive skills contributing to oral inferential
      comprehension in young children with developmental language disorder.
AB  - BACKGROUND: Children with developmental language disorder (DLD) demonstrate poor
      oral inferential comprehension. Research investigating the skills that underpin
      oral inferential comprehension in young children with DLD is necessary in order
      to better understand and improve inferential comprehension in this population.
      AIMS: To profile the language and cognitive skills that contribute to oral
      inferential comprehension in young children with DLD. METHODS & PROCEDURES:
      Seventy-six children aged 5-6 years with a diagnosis of DLD were assessed on a
      wide range of language and cognitive measures. Oral inferential comprehension of
      narrative was the primary outcome measure. OUTCOMES & RESULTS: Narrative
      macrostructure and microstructure, literal comprehension, vocabulary,
      phonological loop, and theory of mind were significant predictors of inferential
      comprehension in bivariate analyses. However, multivariate regression analysis
      indicated that only narrative retell macrostructure and theory of mind
      contributed a significant amount of unique variance to inferential comprehension.
      CONCLUSIONS & IMPLICATIONS: This study profiled the skills contributing to oral
      inferential comprehension in young children with DLD, to support the clinical and
      theoretical understanding of the ability in this population. The findings have
      implications for future intervention studies.

PMID- 30294838
TI  - On the improvement of CBCT image quality for soft tissue-based SRS localization.
AB  - PURPOSE: We explore the optimal cone-beam CT (CBCT) acquisition parameters to
      improve CBCT image quality to enhance intracranial stereotactic radiosurgery
      (SRS) localization and also assess the imaging dose levels associated with each
      imaging protocol. METHODS: Twenty-six CBCT acquisition protocols were generated
      on an Edge(r) linear accelerator (Varian Medical Systems, Palo Alto, CA) with
      different x-ray tube current and potential settings, gantry rotation
      trajectories, and gantry rotation speeds. To assess image quality, images of the
      Catphan 504 phantom were analyzed to evaluate the following image quality
      metrics: uniformity, HU constancy, spatial resolution, low contrast detection,
      noise level, and contrast-to-noise ratio (CNR). To evaluate the imaging dose for
      each protocol, the cone-beam dose index (CBDI) was measured. To validate the
      phantom results, further analysis was performed with an anthropomorphic head
      phantom as well as image data acquired for a clinical SRS patient. RESULTS: The
      Catphan data indicates that adjusting acquisition parameters had direct effects
      on the image noise level, low contrast detection, and CNR, but had minimal
      effects on uniformity, HU constancy, and spatial resolution. The noise level was
      reduced from 34.5 +/- 0.3 to 18.5 +/- 0.2 HU with a four-fold reduction in gantry
      speed, and to 18.7 +/- 0.2 HU with a four-fold increase in tube current. Overall,
      the noise level was found to be proportional to inverse square root of imaging
      dose, and imaging dose was proportional to the product of total tube current-time
      product and the cube of the x-ray potential. Analysis of the anthropomorphic head
      phantom data and clinical SRS imaging data also indicates that noise is reduced
      with imaging dose increase. CONCLUSIONS: Our results indicate that optimization
      of the imaging protocol, and thereby an increase in the imaging dose, is
      warranted for improved soft-tissue visualization for intracranial SRS.

PMID- 30294840
TI  - Strangulated obturator hernia as an unusual cause of small bowel obstruction.

PMID- 30294841
TI  - Can alternative epitope mapping approaches increase the impact of B-cell epitopes
      in food allergy diagnostics?
AB  - In vitro allergy diagnostics are currently based on the detection of specific IgE
      binding on intact allergens or a mixture thereof. This approach has drawbacks as
      it may yield false-negative and/or false-positive results. Thus, we reviewed the
      impact of known B-cell epitopes of food allergens to predict transience or
      persistence, tolerance or allergy and the severity of an allergic reaction and to
      examine new epitope mapping strategies meant to improve serum-based allergy
      diagnostics. Recent epitope mapping approaches have been worthwhile in epitope
      identification and may increase the specificity of allergy diagnostics by using
      epitopes predominately recognized by allergic patients in some cases. However,
      these approaches did not lead to discrimination between clinically relevant and
      irrelevant epitopes so far, since the polyclonal serum IgE-binding epitope
      spectrum seems to be too individual, independent of the disease status of the
      patients. New epitope mapping strategies are necessary to overcome these
      obstacles. The use of patient-derived monoclonal antibodies instead of patient
      sera for functional characterization of clinically relevant and irrelevant
      epitope combinations, distinguished by their ability to induce degranulation,
      might be a promising approach to gain more insight into the allergic reaction and
      to improve serum-based allergy diagnostics.

PMID- 30294842
TI  - Normal weight metabolically unhealthy phenotype in youth: do definitions matter?
AB  - BACKGROUND: Normal weight metabolically unhealthy (NWMU) adults are at increased
      risk of cardiometabolic disease, however little is known regarding NWMU children.
      OBJECTIVES: We examined the associations between existing definitions of NWMU in
      children aged 8-10 years and insulin sensitivity (IS) and secretion 2 years
      later. METHODS: Data stem from the QUALITY cohort of 630 Caucasian youth, 8-10
      years old at baseline, with at least one obese biological parent. Of these, 322
      normal weight children were classified as NWMU using 4 definitions. At 10-12
      years, IS was measured with the Matsuda-insulin sensitivity index; insulin
      secretion was measured with the ratio of the area under the curve (AUC) of
      insulin to the AUC of glucose over a 2-hour OGTT. Multiple linear regression
      models were used. RESULTS: Because few children met the existing definitions of
      metabolic syndrome, associations were examined for less stringent definitions
      (e.g. having 2 vs no risk factors). At baseline, IS was lower in NWMU children
      compared to children with no risk factors (virtually all definitions). Moreover,
      after 2 years, IS was 20.5% lower in NWMU children with 1 or more risk factors,
      and 30.4% lower in those with 2 or more risk factors compared to those with none.
      Insulin secretion was not predicted by components of the metabolic syndrome.
      CONCLUSION: Existing definitions of NWMU youth performed relatively similarly in
      predicting IS as youth entered puberty. Children with one or more components of
      metabolic syndrome - even when of normal weight - have significantly lower
      insulin sensitivity over time. This article is protected by copyright. All rights
      reserved.

PMID- 30294843
TI  - Evaluation of controlled-release devices for providing chromium sesquioxide and
      zinc in Huacaya alpacas at pasture.
AB  - OBJECTIVE: To assess the effectiveness of controlled-release devices (CRDs) for
      providing zinc and for estimating faecal output in alpacas and sheep at pasture.
      METHODS: The study groups of 10 alpacas and 10 sheep at pasture were paired
      within species and allocated at random to receive by mouth either one CRD
      containing chromium sesquioxide designed to function for at least 21 days or two
      CRDs, one containing chromium sesquioxide and the other zinc oxide designed to
      release over a nominal 60-day period. Faecal concentrations of chromium, zinc and
      ash, blood and plasma concentrations of zinc and plasma activity of alkaline
      phosphatase (ALP) were measured over a period of 117 days after treatment.
      RESULTS: The mean faecal chromium excretion profiles suggested that the CRDs
      performed in a similar manner in both species, releasing chromium for nearly 30
      days in alpacas and for slightly more than 30 days in sheep. Using a common
      predetermined release rate of chromium from the CRDs, the daily faecal outputs of
      alpacas and sheep were estimated to be 0.54 kg dry matter and 0.33 kg dry matter,
      respectively. The CRD containing zinc oxide provided after 1 week an estimated
      daily release rate of 40 mg zinc with a lifetime of between 60 and 70 days in
      both species. The additional zinc did not elicit a response in blood zinc
      concentrations or in plasma ALP activity. CONCLUSION: The CRDs were retained in
      the gastrointestinal tracts of the alpacas and sheep and both types functioned as
      expected. The CRD delivering chromium sesquioxide at a known release rate
      provided an estimate of faecal dry matter output over a period of almost 3 weeks
      and the CRD formulated to deliver supplementary zinc did so at the nominal
      release rate over a period of approximately 60 days in both species. These data
      indicated that the standard sheep CRD is applicable for use in alpacas.

PMID- 30294844
TI  - The community and ecosystem consequences of intraspecific diversity: a meta
      analysis.
AB  - Understanding the relationships between biodiversity and ecosystem functioning
      has major implications. Biodiversity-ecosystem functioning relationships are
      generally investigated at the interspecific level, although intraspecific
      diversity (i.e. within-species diversity) is increasingly perceived as an
      important ecological facet of biodiversity. Here, we provide a quantitative and
      integrative synthesis testing, across diverse plant and animal species, whether
      intraspecific diversity is a major driver of community dynamics and ecosystem
      functioning. We specifically tested (i) whether the number of
      genotypes/phenotypes (i.e. intraspecific richness) or the specific identity of
      genotypes/phenotypes (i.e. intraspecific variation) in populations modulate the
      structure of communities and the functioning of ecosystems, (ii) whether the
      ecological effects of intraspecific richness and variation are strong in
      magnitude, and (iii) whether these effects vary among taxonomic groups and
      ecological responses. We found a non-linear relationship between intraspecific
      richness and community and ecosystem dynamics that follows a saturating curve
      shape, as observed for biodiversity-function relationships measured at the
      interspecific level. Importantly, intraspecific richness modulated ecological
      dynamics with a magnitude that was equal to that previously reported for
      interspecific richness. Our results further confirm, based on a database
      containing more than 50 species, that intraspecific variation also has
      substantial effects on ecological dynamics. We demonstrated that the effects of
      intraspecific variation are twice as high as expected by chance, and that they
      might have been underestimated previously. Finally, we found that the ecological
      effects of intraspecific variation are not homogeneous and are actually stronger
      when intraspecific variation is manipulated in primary producers than in consumer
      species, and when they are measured at the ecosystem rather than at the community
      level. Overall, we demonstrated that the two facets of intraspecific diversity
      (richness and variation) can both strongly affect community and ecosystem
      dynamics, which reveals the pivotal role of within-species biodiversity for
      understanding ecological dynamics.

PMID- 30294845
TI  - Protection of brain development by antenatal magnesium sulphate for infants born
      preterm.
AB  - Cerebral palsy (CP) remains the most significant neurological disorder associated
      with preterm birth. It disrupts quality of life and places huge cost burdens on
      society. Antenatal magnesium sulphate administration to females before 32 weeks'
      gestation has proven to be an effective intervention to reduce the rate of CP. In
      models of hypoxia, hypoxia-ischemia, inflammation, and excitotoxicity in various
      animal species, magnesium sulphate preconditioning decreased the resulting lesion
      sizes and inflammatory cytokine levels, prevented cell death, and improved long
      term cognitive and motor behaviours. In humans, meta-analyses of five randomized
      controlled trials using magnesium sulphate as a neuroprotectant showed prevention
      of CP at 2 years. The benefit remained consistent regardless of gestational age,
      cause of preterm birth, and total dose received. Antenatal magnesium sulphate
      treatment is now recommended by the World Health Organization and by many
      obstetric societies. Its cost-effectiveness further justifies its widespread
      implementation. WHAT THIS PAPER ADDS: Neuroprotective effect of magnesium
      sulphate to reduce cerebral palsy in infants born preterm when administered to
      females at risk of imminent preterm birth. Neuroprotection regardless of
      gestational age, cause of preterm birth, and total dose. Antenatal magnesium
      sulphate treatment has good cost-effectiveness.

PMID- 30294846
TI  - Demographic and clinical features of hidradenitis suppurativa in Korea.
AB  - Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin
      disorder. Although several epidemiological studies have been conducted in Western
      countries, such data regarding Asian populations are scarce. In this study, we
      sought to investigate the demographic and clinical features of HS in Korea. A
      total of 438 patients, diagnosed with HS from May 2007 to April 2017, were
      enrolled and the electronic medical record of each patient was reviewed. Male
      patients were predominant with a male : female ratio of 2.5:1. Mean age of
      disease onset was 23.9 years and most patients had no family history. The most
      frequently affected area was the buttocks, followed by axillae and groin. Acne
      and diabetes mellitus were the most prevalent associated diseases and no patients
      with inflammatory bowel diseases were observed. In the univariable analysis, male
      patients had severe diseases compared with females with an odds ratio (OR) of
      1.790. Two or more affected body regions were associated with HS severity with an
      OR of 1.693. While involvement of the perineum (OR, 4.067) and buttocks (OR,
      1.471) tended to be associated with increased severity of the disease, the
      inguinal area (OR, 0.620) showed a tendency to be inversely associated with the
      severity. In multivariable analysis, identified risk factors were the involvement
      of the perineum (OR, 3.819) and buttocks (OR, 2.288). Smoking status and high
      body mass index seemed to be associated with more severe diseases. Our results
      will provide clinical characteristics of HS patients in Asia and help to broaden
      understanding of HS.

PMID- 30294847
TI  - Loop ileostomy reversal after laparoscopic versus open rectal resection.
AB  - BACKGROUND: One of the potential advantages of laparoscopic abdominal surgery is
      in reducing the development of adhesions, making later surgery easier. The
      purpose of this study is to determine whether using the laparoscopic versus open
      approach for a rectal resection with a diverting ileostomy affects the speed and
      safety of subsequent ileostomy reversal. METHODS: This is a retrospective study
      using patients who underwent ileostomy reversal following a rectal cancer
      resection with curative intent with a diverting ileostomy at the University
      Hospital Geelong between January 2006 and June 2017. Demographic information,
      operative technique and histological staging for the initial resection were
      recorded. Theatre time and complication rates for the ileostomy reversal were
      also recorded. RESULTS: A total of 82 patients were included in this study (22
      had laparoscopic resections as the primary operation, 50 had open resections and
      10 had laparoscopic converted to open resections). The three groups were similar
      in age, body mass index, American Society of Anesthesiologists score and
      proportion undergoing chemoradiotherapy. Median (range) theatre time for
      ileostomy reversal was 118 (50-200) min after a laparoscopic resection, 80 (30
      360) min after a laparoscopic converted to open resection and 65 (50-160) min
      after an open resection (P = 0.009). Complication rates after ileostomy reversal
      were similar between the three groups (P = 0.97). CONCLUSION: Ileostomy reversal
      took longer to perform if the primary rectal resection was performed
      laparoscopically.

PMID- 30294848
TI  - Use of gastrografin in the management of faecal impaction in patients with severe
      chronic constipation: a randomized clinical trial.
AB  - BACKGROUND/AIM: Faecal impaction (FI) is a common cause of lower gastrointestinal
      tract obstruction. Gastrografin is a water-soluble radiologic contrast agent that
      may be orally or rectally administered, with proved therapeutic benefits in
      adhesive small bowel obstruction. Enemas have long been advocated as the best
      treatment for FI. The purpose of this study was to demonstrate that enteral
      administration of gastrografin might be more effective than enema in FI treatment
      inducing intestinal obstruction. METHODS: A double-blinded, controlled and
      randomized trial was conducted. Participants received 100 mL of gastrografin
      (gastrografin group) through nasointestinal tube or enemas (enema group) once
      daily for six consecutive days. Successful faecal disimpaction, FI time to
      resolution, Bristol Stool Scale, constipation severity, symptom assessment and
      adverse events were evaluated. RESULTS: A total of 124 patients were eligible,
      but only 83 were enrolled to this trial (mean age: 44 +/- 15.8 years). Forty-two
      patients received enemas, and 41 patients received gastrografin, with six
      dropouts in each group. Successful disimpaction was achieved with enemas (69.44%)
      and gastrografin (88.57%; P = 0.034), mean duration of impaction was strikingly
      different between the two groups (67.13 versus 31.67, respectively; P < 0.01).
      Constipation severity and symptom assessment were significantly reduced in the
      gastrografin group. CONCLUSION: Gastrografin given through nasointestinal tube
      was more effective than enema in the treatment of FI inducing colon obstruction.
      Gastrografin might be taken into consideration as an effective and safe
      therapeutic option for FI.

PMID- 30294849
TI  - Intussusception of colonic lipoma with ischaemic necrosis: a new colonoscopic
      finding.

PMID- 30294850
TI  - Morbidity and mortality in cervical spine injuries in the elderly.
AB  - BACKGROUND: The aim of our study was to identify the demographics and
      complications in elderly cervical spine injuries and predictive factors for
      surgery, complications and mortality. We hypothesized younger healthier patients
      were more likely to undergo surgical intervention. METHODS: A retrospective
      review of 225 consecutive patients aged 65 years and over with cervical spine
      injuries was carried out over a 3-year period. RESULTS: There were 113 males and
      112 females with an average of 79.7 years (range 65-98). The most common fracture
      was C2 peg type (21.8%). Five patients had complete spinal cord injury (2.2%), 25
      had incomplete spinal cord injury (11.1%) and 84% were neurologically intact.
      Fifty-four patients were managed operatively (24%), while 171 patients were
      managed non-operatively (76%). The operative group had higher rates of pneumonia
      (odds ratio (OR) 5.3, 95% confidence interval (CI) 2.6-10.7, P < 0.01), cardiac
      arrhythmia (OR 4.1, 95% CI 1.5-11.2, P < 0.01) and respiratory failure (OR 2.6,
      95% CI 1.2-5.5, P < 0.05). There was no difference in mortality between the
      operative and non-operative group (18.5% and 12.9%, P = 0.3). Patients with
      complete spinal cord injury had 100% mortality. Significant predictive factors
      for complications and death were neurological deficits, comorbidities and the
      presence of other injuries (P < 0.05). Surgery was not predictive for death and
      the operative group was younger than the non-operative group (P < 0.05).
      CONCLUSIONS: In the setting of a high complication rate, consideration should be
      given to palliation in elderly patients with complete spinal cord injury and
      there must be good rational for surgery.

PMID- 30294852
TI  - Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles.
AB  - Targeted delivery of anticancer drugs with nanocarriers can reduce side effects
      and ameliorate therapeutic efficacy. However, poorly perfused and dysfunctional
      tumor vessels limit the transport of the payload into solid tumors. The use of
      tumor-penetrating nanocarriers might enhance tumor uptake and antitumor effects.
      A peptide containing a tissue-penetrating (TP) consensus motif, capable of
      recognizing neuropilin-1, is here fused to a neuroblastoma-targeting peptide
      (pep) previously developed. Neuroblastoma cell lines and cells derived from both
      xenografts and high-risk neuroblastoma patients show overexpression of neuropilin
      1. In vitro studies reveal that TP-pep binds cell lines and cells derived from
      neuroblastoma patients more efficiently than pep. TP-pep, after coupling to
      doxorubicin-containing stealth liposomes (TP-pep-SL[doxorubicin]), enhances their
      uptake by cells and cytotoxic effects in vitro, while increasing tumor-binding
      capability and homing in vivo. TP-pep-SL[doxorubicin] treatment enhances the
      Evans Blue dye accumulation in tumors but not in nontumor tissues, pointing to
      selective increase of vascular permeability in tumor tissues. Compared to pep
      SL[doxorubicin], TP-pep-SL[doxorubicin] shows an increased antineuroblastoma
      activity in three neuroblastoma animal models mimicking the growth of
      neuroblastoma in humans. The enhancement of drug penetration in tumors by TP-pep
      targeted nanoparticles may represent an innovative strategy for neuroblastoma.

PMID- 30294853
TI  - Ultrasound-guided catheterization of the femoral artery in a canine model of
      acute hemorrhagic shock.
AB  - OBJECTIVE: To describe a technique for gaining ultrasound-guided access to the
      femoral artery in an experimental model of acute hemorrhagic shock in
      anesthetized dogs. CASE SERIES SUMMARY: Five healthy, purpose-bred adult male
      intact Beagles were enrolled in a respiratory mechanics study under general
      anesthesia. Upon completion of the primary study a hypovolemic state was induced
      by blood removal to achieve a mean arterial pressure <= 55 mm Hg. Dogs were
      positioned in dorsal recumbency with the hind limb extended caudally. An
      ultrasound probe was applied to the medial aspect of the hind limb and positioned
      in the transverse orientation so that the femoral artery was visualized in its
      short axis. The artery was identified by lack of compression and presence of
      visible pulsation. The probe was rotated 90 degrees  into the longitudinal
      orientation such that the artery was visualized in its long axis. Under
      ultrasound guidance a 19-gauge introducer needle was advanced into the lumen of
      the femoral artery. Using a modified Seldinger technique the needle was removed
      and a catheter was placed in the femoral artery. Correct placement of the
      catheter was verified by observation of the characteristic arterial blood
      pressure waveform. Upon completion of the study dogs were humanely euthanized.
      The femoral artery was successfully catheterized in 4/5 dogs and a hematoma was
      reported in 1/5 dogs. NEW OR UNIQUE INFORMATION PROVIDED: Ultrasound-guided
      femoral artery catheterization is feasible on anesthetized dogs with concurrent
      acute hemorrhagic shock.

PMID- 30294851
TI  - Equine asthma: Integrative biologic relevance of a recently proposed
      nomenclature.
AB  - The term "equine asthma" has been proposed as a unifying descriptor of
      inflammatory airway disease (IAD), recurrent airway obstruction (RAO), and summer
      pasture-associated obstructive airway disease. Whilst the term will increase
      comprehensibility for both the lay and scientific communities, its biologic
      relevance must be compared and contrasted to asthma in human medicine,
      recognizing the limited availability of peer-reviewed equine-derived data, which
      are largely restricted to clinical signs, measures of airway obstruction and
      inflammation and response to therapy. Such limitations constrain meaningful
      comparisons with human asthma phenotypes. Suggested minimum inclusion criteria
      supporting the term asthma, as well as similarities and differences between IAD,
      RAO, and multiple human asthma phenotypes are discussed. Furthermore, differences
      between phenotype and severity are described, and typical features for equine
      asthma subcategories are proposed. Based on shared features, we conclude that
      mild/moderate (IAD) and severe (RAO) equine asthma are biologically appropriate
      models for both allergic and non-allergic human asthma, with RAO (severe equine
      asthma) also being an appropriate model for late-onset asthma. With the
      development of new biologic treatments in humans and the application of more
      targeted therapeutic approaches in the horse, it would appear appropriate to
      further investigate the allergic (Th-2) and non-allergic (non-Th-2) phenotypes of
      equine asthma. Further research is required to more fully determine the potential
      clinical utility of phenotype classification.

PMID- 30294854
TI  - Is obstructive sleep apnea associated with ventricular tachycardia? A
      retrospective study from the National Inpatient Sample and a literature review on
      the pathogenesis of Obstructive Sleep Apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a known independent risk factor for
      a multiple cardiovascular morbidities and mortality. The association of OSA and
      ventricular arrhythmias is less well understood. The aim of this analysis is to
      study the relationship between OSA and ventricular tachyarrhythmias. HYPOTHESIS:
      OSA is associated with increased ventricular arrhythmias. METHODS: Data from the
      national inpatient sample (NIS) 2012 to 2014, were reviewed. Discharges
      associated with OSA were identified as the target population using the relevant
      ICD-9-CM codes. The primary outcome was a diagnosis of ventricular tachycardia
      (VT) in the OSA population. Secondary outcomes include the rate of ventricular
      fibrillation (VF) and cardiac arrest. Multivariable analyses were performed to
      examine the association of VT with multiple potential confounding clinical
      variables. RESULTS: Of 18 013 878 health encounters, 943 978 subjects (5.24%) had
      a diagnosis of OSA. VT and VF were more prevalent among patients with OSA
      compared to those without a diagnosis of OSA (2.24% vs 1.16%; P < 0.001 and 0.3%
      vs 0.2%; P < 0.001, respectively). Odds ratio for cardiac arrest in OSA group was
      not statistically significant (1, 95% confidence interval 0.97-1.02, P < 0.76).
      In unadjusted analyses, all examined comorbidities were significantly more common
      in those with OSA, including diabetes mellitus, hypertension, chronic kidney
      disease, acute coronary syndrome, and heart failure. CONCLUSION: OSA is
      associated with increased rates of ventricular tachyarrhythmia.

PMID- 30294855
TI  - Regulation by biotic stress of tannins biosynthesis in Quercus ilex: crosstalk
      between defoliation and Phytophthora cinnamomi infection.
AB  - Sustainability of the Mediterranean forest is threatened by oak decline, a
      disease of holm oak and other Quercus species that is initiated by infection with
      the oomycete Phytophthora cinnamomi. Focusing on the role of tannins in the
      chemical defense of plants, this work investigated whether tannins content in
      Quercus ilex is regulated by biotic stress. Screening of published genomes
      allowed the identification of Quercus sequences encoding enzymes for early steps
      of the biosynthesis of phenolic compounds, like hydrolysable tannins and
      condensed tannins (CT) among others, plus genes involved in the late steps of CT
      biosynthesis. Four days after treatment of Q. ilex seedlings by mechanical
      defoliation, P. cinnamomi infection and both stressors simultaneously, mRNA
      concentrations for tannins biosynthesis enzymes were measured in leaves. Among
      the transcript amount for shikimate dehydrogenase (SDH, EC 1.1.1.25),
      anthocyanidin reductase (EC 1.3.1.77), anthocyanidin synthase (EC 1.14.11.19) and
      leucoanthocyanidine reductase (EC 1.17.1.3), defoliation induced gene expression
      for SDH2 isoenzyme. About 4 days after infection of roots by P. cinnamomi, this
      up-regulation was canceled and SDH enzyme activity decreased. Furthermore, during
      this late stage of biotrophic interaction the pathogen switched off the
      correlation engaged by defoliation between the expression of SDH1 and SDH2
      encoding genes and chemical defenses corresponding to total tannins, which were
      down-regulated. Thus, tannins biosynthesis in seedlings of Q. ilex is induced
      after mechanical defoliation whereas infection by the pathogen interferes with
      this regulation, potentially increasing the susceptibility of plants to herbivory
      and aggravating the impact of biotic stress.

PMID- 30294856
TI  - Current mismatch repair deficiency tumor testing practices and capabilities: A
      survey of Australian pathology providers.
AB  - AIM & METHODS: An electronic survey of the Royal College of Pathologists of
      Australasia accredited pathology services was conducted to assess Lynch syndrome
      tumor screening practices and to identify barriers and capabilities to screen
      newly diagnosed colorectal and endometrial tumors in Australia. RESULTS:
      Australia lacks a national policy for universal mismatch repair-deficient (dMMR)
      testing of incident colorectal and endometrial tumors cases. Routine Lynch
      syndrome tumor screening program for colorectal and/or endometrial tumors was
      applied by 95% (37/39) of laboratories. Tumor dMMR screening methods varied; MMR
      protein immunohistochemistry (IHC) alone was undertaken by 77% of 39
      laboratories, 18% performed both IHC and microsatellite instability testing, 5%
      did not have the capacity to perform in-house testing. For colorectal tumors, 47%
      (17/36) reported following a universal approach without age limit, 30% (11/36)
      tested only "red flag" cases; 6% (3/36) on clinician request only. For
      endometrial tumors, 37% (12/33) reported clinician request generated testing, 27%
      (9/33) were screening only "red flag" cases, and 12% (4/33) carried out universal
      screening without an age criteria. BRAF V600E mutation testing of colorectal
      tumors demonstrating aberrant MLH1 protein expression by IHC was the most common
      secondary tumor test, with 53% of laboratories performing the test; 15% of
      laboratories also applied the BRAF V600E test to endometrial tumors with aberrant
      MLH1 expression despite no evidence for its utility. Tumor testing for MLH1
      promoter methylation was performed by less than 15% laboratories. CONCLUSION:
      Although use of tumor screening for evidence of dMMR is widely available,
      protocols for its use in Australia vary widely. This national survey provides a
      snapshot of the current availability and practice of tumor dMMR screening and
      identifies the need for a uniform national testing policy.

PMID- 30294857
TI  - Assessment of plasma lactate and core-peripheral temperature gradient in
      association with stages of naturally occurring myxomatous mitral valve disease in
      dogs.
AB  - OBJECTIVE: To evaluate plasma lactate concentrations and core-peripheral
      temperature gradients as perfusion parameters in dogs with heart failure caused
      by myxomatous mitral valve disease (MMVD) and to determine whether the above
      perfusion parameters are correlated with disease stages. DESIGN: Prospective
      observational study. SETTING: University teaching hospital. ANIMALS: After
      excluding 129 dogs because of exclusion criteria, 7 dogs with heart failure
      classified as stage B2 and 10 dogs classified as stage C according to the
      American Heart Association (AHA)/American College of Cardiology (ACC) were
      included in the study. Six dogs without MMVD were evaluated as the control group.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the evaluated
      parameters, the plasma lactate concentrations were increased in stage C (median
      3.70 mmol/L [33.3 mg/dL], interquartile range (IQR) 0.72 mmol/L [6.5 mg/dL])
      compared with those in the control (median 2.80 mmol/L [25.2 mg/dL], IQR 0.8
      mmol/L [7.2 mg/dL]; P = 0.024) and stage B2 groups (median 2.70 mmol/L [24.3
      mg/dL], IQR 1.8 mmol/L [16.2 mg/dL]; P = 0.045). Significant differences were not
      observed in the core-peripheral temperature gradients among the control, stage
      B2, and stage C dogs. CONCLUSIONS: Dogs with structural heart disease as a result
      of MMVD may have occult tissue hypoperfusion in stage C that is demonstrated by
      hyperlactatemia.

PMID- 30294858
TI  - A NanoFlare-Based Strategy for In Situ Tumor Margin Demarcation and Neoadjuvant
      Gene/Photothermal Therapy.
AB  - Accurate tumor margin demarcation in situ remains a paramount challenge. Herein,
      a NanoFlare (also known as spherical-nucleic-acid technology) based strategy is
      reported for in situ tumor margin delineation by transforming and amplifying the
      pathophysiological redox signals of tumor microenvironment. The NanoFlare
      designed (named AuNS-ASON) is based on gold nanostar (AuNS) coated with a dense
      shell of disulfide bridge-inserted and cyanine dyes-labeled antisense
      oligonucleotides (ASON) targeting survivin mRNA. The unique anisotropic ASON
      spike nanostructure endows the AuNS-ASON with universal cellular internalization
      of tumor cells, while the disulfide bridge inserted confers response specificity
      toward redox activation. In vitro experiments demonstrate that the AuNS-ASON can
      discriminate tumor cells rapidly with activated fluorescence signals (>100-fold)
      in 2 h, and further achieve synergistic gene/photothermal tumor cells ablation
      upon near-infrared laser irradiation. Remarkably, in situ tumor margin
      delineation with high accuracy and outstanding spatial resolution (<100 um) in
      mice bearing different tumors is obtained based on the AuNS-ASON, providing
      intraoperative guidance for tumor resection. Moreover, the AuNS-ASON can enable
      efficient neoadjuvant gene/photothermal therapy before surgery to reduce tumor
      extent and increase resectability. The concept of NanoFlare-based
      microenvironment signal transformation and amplification could be used as a
      general strategy to guide the design of activatable nanoprobes for cancer
      theranostics.

PMID- 30294859
TI  - Expression of neutrophil surface markers in icteric neonates before and after
      phototherapy.
AB  - BACKGROUND: Jaundice due to indirect hyperbilirubinemia affects more than 60% of
      neonates and phototherapy is the treatment for severe types. There are no
      previous studies evaluating the effect of phototherapy on the function of
      neonates neutrophils. The aim of this study was to assess and compare the
      function of neutrophils by measuring the expression of neutrophils main surface
      markers in icteric neonates before and after phototherapy. METHODS: Neonates at a
      gestational age >=35 weeks and birth weight >=2,000 g who met the American
      Academy of Pediatrics criteria for phototherapy were included. Flow cytometry
      evaluation of the mean fluorescence intensities of CD10, CD11b, CD11c, CD15,
      CD16, CD18, CD62L, CD64, and CD66acde was performed before and 24 h after the
      initiation of phototherapy. RESULTS: Twenty-five neonates at a mean age of 53 h
      of life were included in the study with a mean bilirubin level of 13.60 +/- 2.85
      mg/dL. There was no statistical difference in the expression of CD11b, CD15,
      CD18, CD62L, and CD64 or in the percentage of neutrophils before and after 24 h
      of phototherapy. There was an increase in the expression of CD10 and CD16 and a
      decrease in the expression of CD11c and CD66acde after 24 h of phototherapy.
      CONCLUSIONS: Newborns submitted to phototherapy had an increase in the expression
      of CD10 and CD16 and a decreased in the expression of CD11c and CD66acde after 24
      h of treatment, which may be related to an anti-inflammatory effect of
      phototherapy.

PMID- 30294860
TI  - Ambient Air Condition for Room-Temperature Deposition of MAPbI3 Films in Highly
      Efficient Solar Cells.
AB  - The power conversion efficiency of perovskite solar cells has been boosted
      rapidly, it has so far exceeded that of commercial polycrystalline silicon solar
      cells. This has prompted great interest in large-scale production and deployment
      of perovskite solar cells. However, state-of-the-art perovskite solar cells are
      fabricated inside gloveboxes and further annealing at high temperatures
      (typically at >100  degrees C for 30 min) is needed. These two required
      conditions are not compatible with, either in the respect to high-throughput or
      thermal budget, a feasible industrial production process. By eliminating the two
      requirements, the deposition of perovskite films both at room temperature and
      under ambient air condition will make the scalable roll-to-roll fabrication
      scheme feasible. Here, the anti-solvent (chloroform) washing is introduced to the
      previously developed hydrochloride-assisted method and demonstrate that the room
      temperature method can be carried out under ambient air condition for MAPbI3 film
      deposition. Through this new procedure, a power conversion efficiency as high as
      17.72% is achieved for MAPbI3 planar devices fabricated under a relative humidity
      of 30% at room temperature. Further, it is revealed that the room-temperature
      process MAPbI3 films show a near monoexponential decay pathway with a long
      photoluminescence lifetime of >400 ns.

PMID- 30294861
TI  - Recombinant mouse calcitonin gene-related peptide secreted by Lactococcus lactis
      inhibits lipopolysaccharide-induced inflammatory response in macrophages.
AB  - We describe the development of a genetically modified strain of lactic acid
      bacteria (gmLAB) capable of producing a recombinant mouse calcitonin gene-related
      peptide (rCGRP). This strain (NZ-CGRP) was generated by introducing a CGRP
      secretion plasmid into Lactococcus lactis NZ9000. Western blotting confirmed the
      secretion of rCGRP in the presence of the inducer nisin. Highly purified rCGRP
      was obtained from the culture supernatants of NZ-CGRP. We demonstrated that
      prophylactic exposure of a culture of mouse peritoneal macrophages to rCGRP
      inhibited lipopolysaccharide (LPS) induction of tumor necrosis factor-alpha (TNF
      alpha). The rCGRP-secreting gmLAB strain holds promise for development as a new
      anti-inflammatory prophylactic.

PMID- 30294863
TI  - Linear nail bed dyschromia: a distinctive dermoscopic feature of nail lichen
      planus.

PMID- 30294862
TI  - Magnetic Shape Memory Turns to Nano: Microstructure Controlled Actuation of Free
      Standing Nanodisks.
AB  - Magnetic shape memory materials hold a great promise for next-generation
      actuation devices and systems for energy conversion, thanks to the intimate
      coupling between structure and magnetism in their martensitic phase. Here novel
      magnetic shape memory free-standing nanodisks are proposed, proving that the lack
      of the substrate constrains enables the exploitation of new microstructure
      controlled actuation mechanisms by the combined application of different stimuli
      i.e., temperature and magnetic field. The results show that a reversible areal
      strain (up to 5.5%) can be achieved and tuned in intensity and sign (i.e., areal
      contraction or expansion) by the application of a magnetic field. The mechanisms
      at the basis of the actuation are investigated by experiments performed at
      different length scales and directly visualized by several electron microscopy
      techniques, including electron holography, showing that thermo/magnetomechanical
      properties can be optimized by engineering the martensitic microstructure through
      epitaxial growth and lateral confinement. These findings represent a step forward
      toward the development of a new class of temperature-field controlled
      nanoactuators and smart nanomaterials.

PMID- 30294864
TI  - Silk Fibroin Microparticles with Hollow Mesoporous Silica Nanocarriers
      Encapsulation for Abdominal Wall Repair.
AB  - Therapeutic vascularization appears to be an effective way of repairing abdominal
      wall defects. Attempts to implement this treatment tend to focus on the
      generation of featured drug carriers with the ability effectively to encapsulate
      the angiogenesis-stimulating agents and control their release to maintain an
      appropriate concentration at the injured area. Here, a new type of composite
      microparticle (CM) composed of silk fibroin (SF) and hollow mesoporous silica
      nanocarriers (HMSNs) is presented for therapeutic agent delivery. The CMs are
      generated by drying microfluidic emulsion templates of HMSN-dispersed SF
      solution. The resultant CMs have a distinctive micro-nanostructure, in which two
      barriers control the drug release. The encapsulated HMSNs increase the drug
      carrying capacity of the CMs, and also form the first barrier via physical
      absorption. The microfluidic SF microparticles not only provide a shell with
      excellent monodispersity and biocompatibility but also form the second barrier
      via efficient encapsulation. Because of these superior properties of the CMs, the
      loaded drugs can be delivered with a satisfactory activity at the required rate,
      making them ideal for implementing therapeutic vascularization and repairing
      abdominal wall defects.

PMID- 30294865
TI  - Sexual activity and life satisfaction in older adults.
AB  - AIM: Based on the concept of successful ageing and research reports on the
      benefits of maintaining sexual activity in mid- to late life, the purpose of the
      current study was to examine the relationship between global life satisfaction
      and sexual satisfaction in adults older than 60 years. The study also analyzed
      the relationship between various forms of sexual activity (genital and non
      genital) and both types of satisfaction. METHODS: Thirty-three men and 50 women
      (N =83) were interviewed by using two structuralized questionnaires. Global life
      satisfaction was measured with Diener's Satisfaction with Life Scale, whereas
      sexual satisfaction and preferences regarding various intimate behaviours (i.e.
      kissing, cuddling, touching partner's intimate body parts, penetration, and
      masturbation) were assessed with a questionnaire devised for the purpose of the
      study. Statistical analyses were conducted to verify the relationships among the
      variables, group differences, and the statistical significance of sexual
      satisfaction as a predictor of global life satisfaction. RESULTS: Most of the
      interviewed subjects have had engaged in sexual activity in the last 1-6 months
      before the study (60%). Participants declared that they mostly engage in subtle
      forms of sexual activity rather than having intercourse. The level of sexual
      activity of older adults was positively associated with both sexual and global
      life satisfaction, but different forms of intimacy had a different impact on
      satisfaction. Gender was not correlated with the level of sexual and global life
      satisfaction. CONCLUSIONS: Sexual satisfaction was a good predictor of global
      life satisfaction in older adults in our study. The participants appeared less
      concerned with the frequency of their intimate activities and more with engaging
      in the type of behaviour they were able to enjoy, which shows that they were
      adapting to the ageing process and potential health issues.

PMID- 30294866
TI  - Transthoracic Echocardiographic Evaluation of Pulmonary Valve Anomalies in
      Pediatric Patients.
AB  - The pulmonary valve normally consists of 3 leaflets supported in a semilunar
      fashion within the sinuses of the pulmonary trunk. Pulmonary leaflet
      malformations, such as congenital single pulmonary cusp absence, bicuspid
      pulmonary valve, and quadricuspid pulmonary valve anomalies, as well as pulmonary
      valve commissural fusion, are seldom identified preoperatively on
      echocardiography. In this study, we report on 5 children with different types of
      pulmonary valve malformations diagnosed by transthoracic echocardiography.

PMID- 30294867
TI  - Photothermal Convection Lithography for Rapid and Direct Assembly of Colloidal
      Plasmonic Nanoparticles on Generic Substrates.
AB  - Controlled assembly of colloidal nanoparticles onto solid substrates generally
      needs to overcome their thermal diffusion in water. For this purpose, several
      techniques that are based on chemical bonding, capillary interactions with
      substrate patterning, optical force, and optofluidic heating of light-absorbing
      substrates are proposed. However, the direct assembly of colloidal nanoparticles
      on generic substrates without chemical linkers and substrate patterning still
      remains challenging. Here, photothermal convection lithography is proposed, which
      allows the rapid placement of colloidal nanoparticles onto the surface of diverse
      solid substrates. It is based on local photothermal heating of colloidal
      nanoparticles by resonant light focusing without substrate heating, which induces
      convective flow. The convective flow, then, forces the colloidal nanoparticles to
      assemble at the illumination point of light. The size of the assembly is
      increased by either increasing the light intensity or illumination time. It is
      shown that three types of colloidal gold nanoparticles with different shapes
      (rod, star, and sphere) can be uniformly assembled by the proposed method. Each
      assembly with a diameter of tens of micrometers can be completed within a minute
      and its patterned arrays can also be achieved rapidly.

PMID- 30294868
TI  - Benzoyl peroxide + chlorhexidine versus chlorhexidine alone skin preparation to
      reduce Propionibacterium acnes: a randomized controlled trial.
AB  - BACKGROUND: Traditional skin preparation for shoulder surgery is not specific for
      Propionibacterium acnes. Topical benzoyl peroxide for 48 h preoperatively has
      been shown to reduce the bacterial load of P. acnes on the skin. Our aim was to
      investigate whether skin preparation with a single application of benzoyl
      peroxide combined with 2% chlorhexidine/alcohol immediately prior to surgery was
      superior to 2% chlorhexidine/alcohol alone at inhibiting P. acnes. METHODS: We
      conducted a single-blinded interventional study. Each shoulder of the participant
      was assigned a different preparation through a randomization process. Two sites
      were assessed per shoulder. The intervention was the application of benzoyl
      peroxide followed by chlorhexidine/alcohol to the shoulder. The control was two
      applications of 2% chlorhexidine/alcohol. Superficial skin swabs for semi
      quantitative culture were taken pre- and post-skin preparation. RESULTS: A total
      of 22 male participants were randomized. All participants were colonized with P.
      acnes on baseline swabs. We found complete inhibition of P. acnes at 14 days at
      80% of sites prepared with benzoyl peroxide + chlorhexidine/alcohol compared with
      86% inhibition at shoulder sites prepared with chlorhexidine alone. CONCLUSION:
      There was no reduction in the growth of P. acnes over 14 days with
      chlorhexidine/alcohol and benzoyl peroxide compared with chlorhexidine alone. On
      the basis of these results, the addition of benzoyl peroxide at the time of
      surgery does not appear to increase the efficacy of the surgical preparation for
      inhibiting P. acnes growth.

PMID- 30294869
TI  - Autistic traits in neurotypical individuals are associated with increased
      landmark use during navigation.
AB  - People adopt two distinct learning strategies during navigation. "Spatial
      learners" navigate by building a cognitive map using environmental landmarks, and
      display more grey matter in the hippocampus. Conversely, "response learners"
      memorize a series of rigid turns to navigate and display more grey matter in the
      caudate nucleus of the striatum. Evidence has linked these two structures with
      autism spectrum disorder (ASD) and autistic traits in non-clinical populations.
      Both people with ASD and neurotypical people with higher levels of autistic
      traits have been shown to display more grey matter in the hippocampus and less
      functional activity in the caudate nucleus. We therefore tested 56 healthy
      participants who completed the Autism Quotient (AQ) Scale and the 4-on-8 Virtual
      Maze (4/8 VM), which determines the reliance on landmarks during navigation. We
      found that people who relied on landmarks during navigation also displayed
      significantly higher scores on the AQ Scale. Because spatial strategies are
      associated with increased attention to environmental landmark use and are
      supported by the hippocampus, our results provide a potential behavioral
      mechanism linking higher autistic traits (e.g., increased attention to detail and
      increased sensory processes) to increased hippocampal grey matter.

PMID- 30294870
TI  - Microbial translocation and T cell activation are modified by direct-acting
      antiviral therapy in HCV-infected patients.
AB  - BACKGROUND: Microbial translocation from the gut lumen has been involved in the
      pathogenesis of liver damage in hepatitis C virus (HCV) infection. AIM: To
      investigate the impact of direct-acting antiviral treatment on microbial
      translocation and T-cell activation, in patients with hepatitis C-related liver
      disease. METHODS: We enrolled two groups of HCV-infected patients undergoing
      direct-acting antiviral treatment: patients with fibrosis >=F3 according to
      Metavir (Group >=F3); patients with hepatitis C recurrence after liver
      transplantation and Metavir >=F2 (Group Liver Transplantation + >=F2). All
      patients were treated with direct-acting antivirals based on ongoing guidelines.
      Surrogate biomarkers of microbial translocation (plasma concentrations of soluble
      CD14, lipopolysaccharide-binding protein and intestinal fatty acid-binding
      protein) were evaluated at baseline, at first month, at the end of treatment and
      3 months later. T-cell activation was measured by expression of CD38+ HLA-DR at
      the same time points, only in Group >=F3. RESULTS: There were 32 patients in
      Group >=F3 and 13 in Group LT + >=F2. At baseline, levels of soluble-CD14 and
      lipopolysaccharide-binding protein were significantly higher in both groups vs
      healthy controls. Baseline soluble-CD14 correlated with glutamic-oxalacetic
      transaminase (r = 0.384, P = 0.009) and glutamic-pyruvic transaminase (r = 0.293,
      P = 0.05). A significant decrease in plasma levels of surrogate microbial
      translocation biomarkers was observed during and after treatment in the two
      groups although values were not normalised. In Group >=F3, CD38+ HLADR+ T-cell
      expression was significantly decreased by direct-acting antiviral treatment.
      Relapsers (9%) showed higher soluble-CD14 levels at baseline. CONCLUSION:
      Surrogate microbial translocation markers and T cell activation are increased in
      HCV-infected patients with liver fibrosis and decrease during direct-acting
      antiviral treatment.

PMID- 30294871
TI  - BRAF mutation in papillary thyroid cancer-Prevalence and clinical correlation in
      a South-East Asian cohort.
AB  - OBJECTIVE: BRAF mutation is the commonest mutation seen in papillary thyroid
      cancer (PTC), but its prevalence and clinical significance vary across countries.
      We aim to evaluate the prevalence and clinico-pathological correlation of BRAF
      mutation in PTC patients at our centre. STUDY DESIGN: Retrospective cohort study
      of 75 consecutive archival thyroid specimens, whereby BRAF mutation was detected
      using a polymerase chain reaction (PCR) technique and correlated with clinical
      and pathological features and outcomes. SETTING: Tertiary university hospital in
      Singapore. PARTICIPANTS: A total of 75 consecutive histologically proven archival
      thyroid specimens from patients who underwent thyroidectomy for PTC were accrued
      for this study. MAIN OUTCOME MEASURES: Main outcome is to determine the
      prevalence of the BRAF mutation in our South-East Asian population. Secondary aim
      is to correlate the mutational status with adverse pathological features like
      histological variants, multi-focality, lymphovascular invasion and extra
      thyroidal extension, clinical features like demographics, TNM stage, recurrence
      and survival, as well as treatment details like type of surgery performed and
      radioiodine doses. RESULTS: BRAF mutation was detected in 56% (42/75) of PTC. All
      but one BRAF-mutated PTC had the BRAFV600E mutation. BRAF-mutated tumours were
      associated with an advanced T-stage (P = 0.049) and were more likely to have a
      central neck dissection (P = 0.036). There was no significant correlation between
      BRAF mutation status and clinical outcomes. CONCLUSION: The prevalence of BRAF
      mutation is 56%. BRAF mutation-positive tumours were associated with locally
      advanced disease, but not poorer survival.

PMID- 30294872
TI  - The experience of maternity care for migrant women living with female genital
      mutilation: A qualitative synthesis.
AB  - BACKGROUND: Increasing numbers of childbearing women with a history of female
      genital mutilation (FGM) are accessing maternity services in high-income
      countries across the world. For many of these women, their first contact with the
      health services in their host country is when they are pregnant. While the
      clinical consequences of certain categories of FGM are well documented, how high
      risk maternity services - designed to mitigate the obstetric consequences of FGM 
      impact upon women's experience of childbearing is less clear. METHODS: Using a
      meta-synthesis approach, this paper synthesizes 12 qualitative research papers,
      conducted in 5 high-income countries, to explore how migrant women with a history
      of FGM experience maternity care in their host countries. RESULTS: One over
      arching theme and four discrete subthemes of migrant women's experience of the
      maternity services in their host country were identified: feelings of alienation;
      fatalism and divine providence, positive and negative feelings about maternity
      care, different understandings of the birthing process, and feelings about FGM.
      CONCLUSIONS: The findings illustrate that migrant women with a history of FGM
      frequently encounter negative attitudes when accessing the maternity services in
      their host countries. Women's experiences suggest a concerning absence of
      sensitive and empathetic care; a more woman-centered approach is recommended.

PMID- 30294873
TI  - Appropriateness of pediatric outpatient transthoracic echocardiogram orders
      following cessation of an active educational intervention.
AB  - OBJECTIVE: The educational intervention (EI) through the Pediatric Appropriate
      Use of Echocardiography (PAUSE) multicenter study resulted in improved
      appropriateness of transthoracic echocardiogram (TTE) orders at our center. The
      current study evaluated if this pattern persisted after cessation of EI and the
      potential physician characteristics influencing appropriateness. DESIGN:
      Outpatients (<=18 years old) seen for initial evaluation during the EI (July to
      October, 2015) and 6-month post-EI (May to August, 2016) phases were included.
      Comparison was made between TTE rates and appropriateness ratings during EI and
      post-EI phase. Association between TTE rate and appropriateness with physician
      characteristics (age, experience, patient volume, and area of practice) was
      determined using odds ratio. RESULTS: The study included 7781 patients (EI: N =
      4016; post-EI: N = 3765) seen by 31 physicians. Comparison of appropriateness
      ratings in a randomized sample (EI: N = 1270; post-EI: N = 1325 patients) showed
      no significant differences between the two phases (appropriate: 75.2% vs 74.9%, P
      = .960; rarely appropriate 4.1% vs 6.5%, P = .065). Though there was significant
      variability among physicians for TTE order appropriateness (P = .044) and
      ordering rate (P <.001), none of their characteristics were associated with
      appropriateness and only a higher patient volume was associated with decreased
      odds of TTE ordering (OR =0.7). CONCLUSION: The PAUSE study EI resulted in
      maintaining appropriate utilization of TTEs at our center for 6 months following
      its cessation. Though not statistically significant, there was a trend toward
      increase in the proportion of studies for indications designated rarely
      appropriate (R). There was significant physician variability in TTE ordering and
      appropriateness during both phases. Development of EI to reduce physician
      variability and integration of EI with provider workflow may help sustain
      appropriate TTE utilization.

PMID- 30294874
TI  - Organisational learning in hospitals: A concept analysis.
AB  - AIM: To provide a clear definition and description of organisational learning in
      hospitals. BACKGROUND: Organisational learning is a promising strategy nurse
      managers, and leaders can use to improve organisational performance. A clear
      definition and description of organisational learning is necessary to advance
      theory, research and practice in this field. METHODS: Walker & Avant's method was
      used to conduct a concept analysis of organisational learning in hospitals. Data
      sources included 147 empirical studies, 16 review articles, three dictionary
      entries and three book chapters. RESULTS: Organisational learning occurs when
      experiences are translated into positive changes in the organisation's collective
      knowledge, cognition and actions. Organisational context plays a key role in the
      learning process. Other manifestations of the concept are identified.
      CONCLUSIONS: This concept analysis provides a clear definition of organisational
      learning and a description of its defining attributes, antecedents, empirical
      referents and consequences. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers
      and leaders can improve patient and organisational outcomes by creating an
      environment conducive to translating experiences into organisational learning.
      Further research is needed to continue advancing the science of organisational
      learning in hospitals.

PMID- 30294875
TI  - Effect of electrode separation on high-resolution impedance manometry catheters
      for ex vivo animal experiments.
AB  - BACKGROUND: High-resolution impedance manometry (HRIM) catheters are used for
      esophageal reflux and bolus transit studies. Usually, these catheters have
      electrodes spaced at 20 mm intervals that are used for measuring electrical
      impedance between the consecutive electrodes and pressure sensors with 10 mm
      separation. Electrical impedance is a distributed measurement between the
      electrodes, unlike the point measurement of pressure sensors. Thus, the electrode
      separations affect the overall spatiotemporal resolution of the measurement.
      METHODS: A 3D model of the gastrointestinal tract, in which bolus shape and size
      can be modified, was used to simulate the admittance signal response of an
      intraluminal impedance catheter with 10 and 20 mm electrode separation to study
      the distributed sensitivity in the lumen to gain insight on the impedance
      measurement. In addition, experiments on sections of rabbit proximal colon were
      conducted with two catheters with electrode separations of 10 and 20 mm to
      compare the experimental data with the simulated data. KEY RESULTS: Reducing
      electrode spacing from 20 to 10 mm increased sensitivity to diameter change by a
      factor of ten. Admittance and diameter correlated strongly during a myogenic
      contraction with a Pearson's Correlation Coefficient of 0.86 for the custom
      catheter, in comparison with 0.56 for the commercial HRIM catheter. CONCLUSIONS:
      Ten millimeter electrode separation has a better spatiotemporal resolution, and
      unlike 20 mm electrode separation is able to identify myogenic contractions.
      Based on the numerical and experimental data, closer electrode separation should
      be considered for improved spatial resolution.

PMID- 30294876
TI  - Impact of cell cycle dynamics on pathology recognition: Raman imaging study.
AB  - Confocal Raman imaging combined with fluorescence-activated cell sorting was used
      for in vitro studies of cell cultures to look at biochemical differences between
      the cells in different cell phases. To answer the question what is the impact of
      the cell cycle phase on discrimination of pathological cells, the combination of
      several factors was checked: a confluency of cell culture, the cell cycle
      dynamics and development of pathology. Confluency of 70% and 100% results in
      significant phenotypic cell changes that can be also diverse for different
      batches. In 100% confluency cultures, cells from various phases become
      phenotypically very similar and their recognition based on Raman spectra is not
      possible. For lower confluency, spectroscopic differences can be found between
      cell cycle phases (G0 /G1 , S and G2 /M) for control cells and cells incubated
      with tumor necrosis factor alpha (TNF-alpha), but when the mycotoxin cytochalasin
      B is used the Raman signatures of cell phases are not separable. Generally, this
      work shows that heterogeneity between control and inflamed cells can be bigger
      than heterogeneity between cell cycle phases, but it is related to several
      factors, and not always can be treated as a rule.

PMID- 30294877
TI  - Editors' Introduction and Review: Sociolinguistic Variation and Cognitive
      Science.
AB  - Sociolinguists study the interaction between language and society. Variationist
      sociolinguistics - the subfield of sociolinguistics which is the focus of this
      issue - uses empirical and quantitative methods to study the production and
      perception of linguistic variation. Linguistic variation refers to how speakers
      choose between linguistic forms that say the same thing in different ways, with
      the variants differing in their social meaning. For example, how frequently
      someone says fishin' or fishing depends on a number of factors, such as the
      speaker's regional and social background and the formality of the speech event.
      Likewise, if listeners are asked to use a rating scale make judgements about
      speakers who say fishin' or fishing, their ratings depend on what other social
      characteristics are attributed to the speaker. This issue aims to reflect the
      growing number of interactions that bring variationist sociolinguistics into
      contact of different branches of cognitive science. After presenting current
      trends in sociolinguistics, we identify five areas of contact between the two
      fields: cognitive sociolinguistics, sociolinguistic cognition, acquisition of
      variation, computational modeling, and a comparative approach of variation in
      animal communication. We then explain the benefits of interdisciplinary work:
      fostering the study of variability and cultural diversity in cognition; bringing
      together data and modeling; understanding the cognitive mechanisms through which
      sociolinguistic variation is processed; examining indexical meaning; exploring
      links between different levels of grammar; and improving methods of data
      collection and analysis. Finally we explain how the articles in this issue
      contribute to each of these benefits. We conclude by suggesting that
      sociolinguistics holds a strategic position for facing the challenge of building
      theories of language through integrating its linguistic, cognitive, and social
      aspects at the collective and individual levels.

PMID- 30294878
TI  - Reciprocal relationships between self-efficacy, outcome satisfaction, and
      attendance at an exercise programme.
AB  - OBJECTIVES: The objectives of this study were to (i) investigate directional
      influences of self-efficacy, outcome satisfaction, and attendance during an
      exercise programme and (ii) examine the predictive capabilities of self-efficacy
      and outcome satisfaction on participant dropout. METHODS: Adults aged 35-65 years
      were recruited to a 12-month exercise programme. Self-efficacy was collected at
      baseline, three, six, nine, and 12 months, and outcome satisfaction at the same
      time-points except baseline. Cross-lagged panel analyses and logistic regression
      analyses were conducted to examine the primary and secondary objectives,
      respectively. RESULTS: Coping and scheduling self-efficacy had stronger
      reciprocal relationships with outcome satisfaction than task self-efficacy,
      although the strength of these relationships varied across time. Initially, task
      self-efficacy predicted programme attendance. Midway through the programme,
      outcome satisfaction predicted attendance, and by the end of the programme,
      coping self-efficacy was the strongest predictor of attendance. Self-efficacy and
      outcome satisfaction did not predict programme dropout. CONCLUSIONS: The results
      support the reciprocal relationship between outcome satisfaction and scheduling
      and coping self-efficacy and highlight the importance of sequentially targeting
      different beliefs and skills to facilitate successful initiation and maintenance
      of exercise behaviour. Statement of contribution What is already known on this
      subject? Self-efficacy and outcome satisfaction are related to exercise
      behaviour. The relationship between self-efficacy and outcome satisfaction are
      typically considered unidirectional. The longitudinal relationships among self
      efficacy, outcome satisfaction, and physical activity participation are unclear.
      What does this study add? Outcome satisfaction had reciprocal relationships with
      both coping and scheduling self-efficacy for exercise. The importance of self
      efficacy and outcome satisfaction to exercise attendance changes over time. Task
      self-efficacy was the strongest predictor of initial programme attendance. Midway
      through the programme, outcome satisfaction and task self-efficacy were the
      strongest predictors of attendance, and by the end of the programme, coping self
      efficacy was the strongest predictor.

PMID- 30294879
TI  - Cyano Modification on Uridine Decreases Base-Pairing Stability and Specificity
      through Neighboring Disruption in RNA Duplex.
AB  - 5-Cyanomethyluridine (cnm5 U) and 5-cyanouridine (cn5 U), the two uridine
      analogues, were synthesized and incorporated into RNA oligonucleotides. Base
      pairing stability and specificity studies in RNA duplexes indicated that cnm5 U
      slightly decreased the stability of the duplex but retained the base-pairing
      preference. In contrast, cn5 U dramatically decreased both base-pairing stability
      and specificity between U:A and other noncanonical U:G, U:U, and U:C pairs. In
      addition, the cn5 U:G pair was found to be stronger than the cn5 U:A pair and the
      other mismatched pairs in the context of a RNA duplex; this implied that cn5 U
      might slightly prefer to recognize G over A. Our mechanistic studies by molecular
      simulations showed that the cn5 U modification did not directly affect the base
      pairing of the parent nucleotide; instead, it weakened the neighboring base pair
      in the 5' side of the modification in the RNA duplexes. Consistent with the
      simulation data, replacing the Watson-Crick A:U pair to a mismatched C:U pair in
      the 5'-neighboring site did not affect the overall stability of the duplex. Our
      work reveals the significance of the electron-withdrawing cyano group in natural
      tRNA systems and provides two novel building blocks for constructing RNA-based
      therapeutics.

PMID- 30294881
TI  - Distribution of Pacini-Like Lamellar Corpuscles in the Vascular Sheath of the
      Femoral Artery.
AB  - Pacinian corpuscles are vibration-sensing mechanoreceptors that are densely
      distributed in the dermis of the human hand. Although they are also known to
      occur in various other regions/structures throughout the human body, including
      the adventitia of large vessels, their precise distribution and function in
      arteries remain unclear. In the present study, we identified Pacini-like lamellar
      corpuscles (LCs) adjacent to the femoral artery, and investigated their
      distribution with respect to that structure via a histological analysis. We
      identified nine LCs that were localized in the connective tissue surrounding the
      femoral artery and vein. We showed that although their distribution was
      heterogeneous, they were predominantly concentrated on the dorsal side of the
      femoral artery. Immunohistochemical analyses revealed that the identified femoral
      artery LCs exhibited features characteristic of typical LCs located in the dermis
      of the index finger. Thus, the results of the present study contribute to an
      improved understanding of the function of femoral artery LCs. Anat Rec, 301:1809
      1814, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30294880
TI  - MiR-409-3p and MiR-1896 co-operatively participate in IL-17-induced inflammatory
      cytokine production in astrocytes and pathogenesis of EAE mice via targeting
      SOCS3/STAT3 signaling.
AB  - Th17 cells and interleukin-17 (IL-17) have been found to play an important role
      in the pathology of multiple sclerosis (MS) and its animal model, experimental
      autoimmune encephalomyelitis (EAE). Response to IL-17, reactive astrocytes
      accompany with immune cells infiltration and axonal damage in MS/EAE. However,
      the role and the regulatory mechanism of IL-17-activated astrocytes in
      inflammation and in the EAE process still remain largely unknown. Here, we
      elucidated that miR-409-3p and miR-1896, as co-upregulated microRNAs in activated
      astrocytes and in EAE mice, targeted suppressor of cytokine signaling proteins 3
      (SOCS3). Overexpression of miR-409-3p or miR-1896 significantly reduced SOCS3
      expression and increased phosphorylation of STAT3 as well as induced the
      inflammatory cytokines production (IL-1beta, IL-6, IP-10, MCP-1, and KC), CD4+ T
      cells migration and demyelination, in turn aggravating EAE development.
      Importantly, the effects of co-overexpression of miR-409-3p and miR-1896 in vitro
      or in vivo are strongly co-operative. In contrast, simultaneously silenced miR
      409-3p and miR-1896 co-operatively ameliorates inflammation and demyelination in
      the central nervous system of EAE mice. Collectively, our findings highlight that
      miR-409-3p and miR-1896 co-ordinately promote the production of inflammatory
      cytokines in reactive astrocytes through the SOCS3/STAT3 pathway and enhance
      reactive astrocyte-directed chemotaxis of CD4+ T cells, leading to aggravate
      pathogenesis in EAE mice. Co-inhibition of miR-409-3p and miR-1896 may be a
      therapeutic target for treating MS and neuroinflammation.

PMID- 30294882
TI  - Understanding care and outcomes in adolescents and young adult with Cancer: A
      review of the AYA HOPE study.
AB  - Historically, adolescents and young adults (AYA) diagnosed with cancer have been
      an understudied population, and their unique care experiences, needs, and
      outcomes were not well understood. Thus, 10 years ago, the National Cancer
      Institute supported the fielding of the Adolescent and Young Adult Health
      Outcomes and Patient Experiences (AYA HOPE) study to address this gap. We
      recruited individuals diagnosed at ages 15 to 39 with germ cell, Hodgkin and non
      Hodgkin lymphoma, acute lymphoblastic leukemia, and sarcoma from Surveillance,
      Epidemiology, and End Results cancer registries into the first multicenter
      population-based study of medical care, physical, and mental health outcomes for
      AYAs with cancer in the United States. This review of the 17 published
      manuscripts showed low awareness of clinical trials and substantial impact of
      cancer on financial burden, education and work, relationships and family
      planning, and physical and mental health. It highlights the feasibility of a
      longitudinal population-based study and key lessons learned for research on AYAs
      with cancer in and beyond the United States.

PMID- 30294883
TI  - Tissue and organ decellularization in regenerative medicine.
AB  - The advancement and improvement in decellularization methods can be attributed to
      the increasing demand for tissues and organs for transplantation. Decellularized
      tissues and organs, which are free of cells and genetic materials while retaining
      the complex ultrastructure of the extracellular matrix (ECM), can serve as
      scaffolds to subsequently embed cells for transplantation. They have the
      potential to mimic the native physiology of the targeted anatomic site. ECM from
      different tissues and organs harvested from various sources have been applied.
      Many techniques are currently involved in the decellularization process, which
      come along with their own advantages and disadvantages. This review focuses on
      recent developments in decellularization methods, the importance and nature of
      detergents used for decellularization, as well as on the role of the ECM either
      as merely a physical support or as a scaffold in retaining and providing cues for
      cell survival, differentiation and homeostasis. In addition, application, status,
      and perspectives on commercialization of bioproducts derived from decellularized
      tissues and organs are addressed. (c) 2018 American Institute of Chemical
      Engineers Biotechnol. Prog., 2018.

PMID- 30294884
TI  - Biomimetic Nanoemulsions for Oxygen Delivery In Vivo.
AB  - Blood transfusion is oftentimes required for patients suffering from acute trauma
      or undergoing surgical procedures in order to help maintain the body's oxygen
      levels. The continued demand worldwide for blood products is expected to put
      significant strain on available resources and infrastructure. Unfortunately,
      efforts to develop viable alternatives to human red blood cells for transfusion
      are generally unsuccessful. Here, a hybrid natural-synthetic nanodelivery
      platform that combines the biocompatibility of the natural RBC membrane with the
      oxygen-carrying ability of perfluorocarbons is reported. The resulting
      formulation can be stored long-term and exhibits a high capacity for oxygen
      delivery, helping to mitigate the effects of hypoxia in vitro. In an animal model
      of hemorrhagic shock, mice are resuscitated at an efficacy comparable to whole
      blood infusion. By leveraging the advantageous properties of its constituent
      parts, this biomimetic oxygen delivery system may have the potential to address a
      critical need in the clinic.

PMID- 30294885
TI  - Effect of sulfadiazine and trimethoprim on activated sludge performance and
      microbial community dynamics in laboratory-scale membrane bioreactors and
      sequencing batch reactors at 8 degrees C.
AB  - The effect of antibiotics sulfadiazine and trimethoprim on activated sludge
      operated at 8 degrees C was investigated. Performance and microbial communities
      of sequencing batch reactors (SBRs) and Membrane Bioreactors (MBRs) were compared
      before and after the exposure of antibiotics to the synthetic wastewater. The
      results revealed irreversible negative effect of these antibiotics in
      environmentally relevant concentrations on nitrifying microbial community of SBR
      activated sludge. In opposite, MBR sludge demonstrated fast adaptation and more
      stable performance during the antibiotics exposure. Dynamics of microbial
      community was greatly affected by presence of antibiotics. Bacteria from classes
      Betaproteobacteria and Bacteroidetes demonstrated the potential to develop
      antibiotic resistance in both wastewater treatment systems while Actinobacteria
      disappeared from all of the reactors after 60 days of antibiotics exposure.
      Altogether, results showed that operational parameters such as sludge retention
      time (SRT) and reactor configuration had great effect on microbial community
      composition of activated sludge and its vulnerability to antibiotics. Operation
      at long SRT allowed archaea, including ammonium oxidizing species (AOA) such as
      Nitrososphaera viennensis to grow in MBRs. AOA could have an important role in
      stable nitrification performance of MBR-activated sludge as a result of tolerance
      of archaea to antibiotics. (c) 2018 American Institute of Chemical Engineers
      Biotechnol. Prog., 2018.

PMID- 30294886
TI  - A microfluidic chip with gravity-induced unidirectional flow for perfusion cell
      culture.
AB  - Perfusion flow is one of the essential elements and advantages of organ-on-a-chip
      technology. For example, microfluidics have enabled implementation of perfusion
      flow and recapitulation of fluidic environment for vascular endothelial cells.
      The most prevalent method of implementing flow in a chip is to use a pump, which
      requires elaborate manipulation and complex connections, and accompanies a large
      amount of dead volume. Previously we devised a gravity-induced flow system which
      does not require tubing connections, but this method results in bidirectional
      flow to enable recirculation, which is somewhat different from physiological
      blood flow. Here, we have developed a novel microfluidic chip that enables
      gravity-induced, unidirectional flow by using a bypass channel with geometry
      different from the main channel. Human umbilical vein endothelial cells were
      cultured inside the chip and the effect of flow direction was examined. (c) 2018
      American Institute of Chemical Engineers Biotechnol. Prog., 2018.

PMID- 30294887
TI  - Biogas purification via optimal microalgae growth: A literature review.
AB  - In this review, we compare works from the current decade that address the CO2 
      removal from biogas by means of microalgae. The microalgae culture process acts
      as a biochemical absorption process; it is potentially competitive with respect
      to classical and commercial absorption methods due to its additional benefits
      such as availing CO2 for the production of valuable microalgae biomass and being
      an environmentally friendly technique. Nevertheless, the low yield of biogas
      purification translates into the need to use optimal operation strategies that
      render the whole biogas production process economically feasible. A class of
      these strategies requires models capable of reproducing key traits of the
      dynamical behavior of microalgae growth. Thus, without overlooking the classical
      physico-chemical methods for biogas purification, our literature review
      addresses: (i) biogas purification via microalgae and different microalgae growth
      conditions, (ii) approaches that maximize microalgae growth, in order to increase
      CO2 -consumption, and (iii) different models that describe the representative
      characteristics of microalgae growth. This investigation traces a pathway to
      future considerations on optimal biogas purification alternatives by microalgae
      culture processes. (c) 2018 American Institute of Chemical Engineers Biotechnol.
      Prog., 2018.

PMID- 30294888
TI  - Money and relationships online: communication and norm formation in women's
      discussions of couple resource allocation.
AB  - Research on intra-household resource allocation practices has largely ignored the
      role of communication within but especially beyond the household. This article
      shows that discussions engaged in outside of the household shed light on intra
      household deliberation and also contribute to an understanding of how norms are
      formed and used in discussions and negotiations. Using data from the website
      Mumsnet, and grounding our analysis in a framework that combines the literature
      on gender norms in allocation practices with insights from the study of online
      communication, we contribute to the sociological literature on household
      distribution in three ways: first, we show that women use discussion sites like
      Mumsnet to clarify and sometimes contest social norms regarding money and
      relationships; second, we show that users conceive the ability to communicate
      with partners as a source of 'relationship power' and use online discussion with
      other women to develop that skill; third, we argue that sites like Mumsnet
      provide fresh insights into household resource allocation processes. The article
      concludes with a broader discussion of the role of communication in household
      distribution and the value of online data for understanding such processes.

PMID- 30294890
TI  - Arterial damage and cognitive impairment in patients with chronic kidney disease.

PMID- 30294889
TI  - Assessing Escherichia coli metabolism models and simulation approaches in
      phenotype predictions: Validation against experimental data.
AB  - Over the last years, several genome-scale metabolic models (GEMs) and kinetic
      models of Escherichia coli were published. Their predictive performance varies
      according to the evaluation metric considered, the computational simulation
      methods used, and the type/quality of experimental data available. However, the
      GEM approach is often not compared with the kinetic modeling framework. Also, the
      different genome-scale reconstruction versions and simulation methods of mutant
      phenotypes are usually not validated to predict intracellular fluxes using large
      experimental datasets. Here, we intended to (i) systematically evaluate the
      prediction performance of three E. coli GEMs (iJR904, iAF1260, and iJO1366)
      available in the literature according to predictive growth metrics (intracellular
      flux distribution); (ii) assess the reliability of a E. coli GEM in the
      prediction of gene knockout phenotypes when different simulation methods
      (parsimonious flux balance analysis, Minimization of Metabolic Adjustment, linear
      version of MoMA, Regulatory on/off minimization, and Minimization of Metabolites
      Balance) are used; and finally (iii) investigate the flux distribution predictive
      power of the constrained-based modeling approach (selected stoichiometric GEM)
      and compare it with the kinetic modeling approach (two published kinetic models)
      for E. coli central metabolism, in order to assess their accuracy. Results show
      that the phenotype predictions were not significantly sensitive to the metabolic
      models, although the GEM iAF1260 was more accurate in the prediction of central
      carbon fluxes at low dilution rates. Furthermore, we observed that the choice of
      the appropriate simulation method of mutant phenotypes depends on the biological
      question to be addressed. In terms of the two modeling approaches, none
      outperformed the other for all the tested scenarios. (c) 2018 American Institute
      of Chemical Engineers Biotechnol. Prog., 2018.

PMID- 30294891
TI  - Inhibition of key enzymes in the inflammatory pathway by hybrid molecules of
      terpenes and synthetic drugs: In vitro and in silico studies.
AB  - The aim of this work was to compare the anti-inflammatory activity of compounds
      prepared from terpenes and the synthetic drugs ibuprofen and naproxen. The anti
      inflammatory activity of the hybrid compounds was compared with the activity of
      the parent compounds. This was accomplished using in vitro inhibition of
      lipoxygenases (LOX) and COX-2, and in silico docking studies in 15-LOX and COX-2.
      The synthesized hybrids showed an inhibition of COX-2 and LOX between 9.8%-57.4%
      and 0.0%-97.7%, respectively. None of the hybrids showed an improvement in the
      inhibitory effect toward these pro-inflammatory enzymes, compared to the parent
      terpenes and non-steroidal anti-inflammatory drugs. The docking studies allowed
      us to predict the potential binding modes of hybrids 6-15 within COX-2 and 15-LOX
      active sites. The relative affinity of the compounds inside the binding sites
      could be explained by forming non-covalent interactions with most important and
      known amino acids reported for those enzymes. A good correlation (r2  = 0.745)
      between docking energies and inhibition percentages against COX-2 was found. The
      high inhibition obtained for compound 10 against COX-2 was explained by hydrogen
      bond interactions at the enzyme binding site. New synthetic possibilities could
      be obtained from our in silico models, improving the potency of these hybrid
      compounds.

PMID- 30294892
TI  - Unequally into "Us": Characteristics of Individuals in Asymmetrically Committed
      Relationships.
AB  - This study examined characteristics of individuals that are associated with being
      in asymmetrically committed relationships (ACRs), defined as romantic
      relationships in which there was a substantial difference in the commitment
      levels of the partners. These ACRs were studied in a national sample of
      unmarried, opposite-sex romantic relationships (N = 315 couples). Perceiving
      oneself as having more potential alternative partners was associated with
      increased odds of being the less committed partner in an ACR compared to not
      being in an ACR, as was being more attachment avoidant, having more prior
      relationship partners, and having a history of extradyadic sex during the present
      relationship. Additionally, having parents who never married was associated with
      being the less committed partner in an ACR but parental divorce was not. Although
      fewer characteristics were associated with being the more committed partner
      within an ACR, more attachment anxiety was associated with increased odds of
      being in such a position compared to not being in an ACR. We also address how
      some findings change when controlling for commitment levels. Overall, the
      findings advance understanding of commitment in romantic relationships,
      particularly when there are substantial asymmetries involved. Implications for
      both research on asymmetrical commitment as well as practice (e.g., therapy or
      relationship education) are discussed.

PMID- 30294893
TI  - The Effect of Prior Work Experiences on the Preparation and Employment of Early
      Career Midwives.
AB  - INTRODUCTION: Strategic recruitment, preparation, distribution, and retention of
      US midwives requires a solid body of knowledge about midwives' education and
      workforce experiences. Although half of US midwifery education programs currently
      require or prefer prior registered nurse (RN) employment, data are lacking about
      whether and how these criteria influence efforts to scale up the workforce to
      meet reproductive care workforce shortages and maldistributions. METHODS: This
      cross-sectional research used an online survey, developed using the framework of
      Social Cognitive Career Theory. Early-career midwives were contacted through the
      American College of Nurse-Midwives electronic mailing list and social media
      during the fall of 2016. Statistical analysis allowed for linkage of data related
      to the following constructs: personal characteristics, prior RN employment,
      educational experiences, employment situations, career perceptions, and future
      plans. RESULTS: All participants (N = 244) were certified nurse-midwives.
      Compared with those without prior RN employment, midwives with prior RN
      employment were more likely to enroll part-time in distance programs and complete
      single majors or degrees. During enrollment, the 2 groups experienced the same
      degree of mentorship and cultural support and were similarly likely to attend 30
      births and to pass the certification examination on first attempt. In the
      workforce, those with prior RN employment were 6 years older and more likely to
      work full-time. The 2 groups demonstrated no significant differences in their
      career perspectives or future career plans. DISCUSSION: Despite anecdotal
      concerns about training midwives who lack RN work experience, an individual
      without prior RN employment offers the workforce an employee who completes
      midwifery education at a younger age, may be educated more quickly, and is more
      likely to have earned a dual major or degree. Those with prior RN employment are
      more likely to work full-time. Both groups may offer benefits to education and
      the workforce.

PMID- 30294894
TI  - The tetrafascicular nature of the intraventricular conduction system.
AB  - The existence of a tetrafascicular intraventricular conduction system remains
      debatable. A consensus statement ended up with some discrepancies and, despite
      agreeing on the possible existence of an anatomical left septal fascicle, the
      electrocardiographic and vectorcardiographic characteristics of left septal
      fascicular block (LSFB) were not universally accepted. The most important
      criteria requested to confirm the existence of LSFB is its intermittent nature.
      So far, our group has published cases of transient ischemia-induced LSFB and
      phase 4 or bradycardia-dependent LSFB. Finally, anatomical, anatomopathological,
      histological, histopathological, electrocardiographic, vectorcardiographic, body
      surface potential mapping, and electrophysiology studies support the fact that
      the left bundle branch divides into three fascicles or a "fan-like interconnected
      network".

PMID- 30294895
TI  - Data-driven multi-objective optimization via grid compatible simplex technique
      and desirability approach for challenging high throughput chromatography
      applications.
AB  - Recently, a grid compatible Simplex variant has been demonstrated to identify
      optima consistently and rapidly in challenging high throughput (HT) applications
      in early bioprocess development. Here, this method is extended by deploying it to
      multi-objective optimization problems. Three HT chromatography case studies are
      presented, each posing challenging early development situations and including
      three responses which were amalgamated by the adoption of the desirability
      approach. The suitability of a design of experiments (DoE) methodology per case
      study, using regression analysis in addition to the desirability approach, was
      evaluated for a large number of weights and in the presence of stringent and
      lenient performance requirements. Despite the adoption of high-order models, this
      approach had low success in identification of the optimal conditions. For the
      deployment of the Simplex approach, the deterministic specification of the
      weights of the merged responses was avoided by including them as inputs in the
      formulated multi-objective optimization problem, facilitating this way the
      decision making process. This, and the ability of the Simplex method to locate
      optima, rendered the presented approach highly successful in delivering rapidly
      operating conditions, which belonged to the Pareto set and offered a superior and
      balanced performance across all outputs compared to alternatives. Moreover, its
      performance was relatively independent of the starting conditions and required
      sub-minute computations despite its higher order mathematical functionality
      compared to DoE techniques. These evidences support the suitability of the grid
      compatible Simplex method for early bioprocess development studies involving
      complex data trends over multiple responses. (c) 2018 The Authors Biotechnology
      Progress published by Wiley Periodicals, Inc. on behalf of American Institute of
      Chemical Engineers Biotechnol. Prog., 2018.

PMID- 30294896
TI  - Comparison of BMI, waist circumference, and waist-to-height ratio for
      identification of subclinical cardiovascular risk in pediatric kidney transplant
      recipients.
AB  - BACKGROUND: Kidney transplant recipients are at high risk for CV morbidity.
      However, the measure of obesity that best predicts CV risk has not been
      established. OBJECTIVE: A prospective, controlled study was conducted to compare
      the ability of BMI, WC, and WHr to identify CV risk in pediatric kidney
      transplant recipients. METHODS: Transplant recipients, aged 3-20 years, had
      echocardiogram, CIMT, BMI, WC, WHr, blood pressure, lipids, and leptin measured.
      Receiver operating characteristic analysis was used to compare the ability of
      BMI, WC, and WHr to detect a composite adverse CV outcome. Presence of the
      composite outcome was defined by >=3 of the following five criteria: (a) LVH, (b)
      high CIMT, (c) impaired myocardial strain, (d) dyslipidemia, and/or (e)
      hypertension. Multivariate analysis was conducted by generalized estimating
      equation regression. RESULTS: We analyzed 108 visits of 42 transplant recipients.
      Prevalence of obesity by WHr (43.5%) was higher than BMI (24.1%) and WC (12.0%).
      Proportion of WHr-obese who met criteria for the adverse CV outcome was higher
      (62.2%) than BMI (34.6%) and WC-obese (33.3%). Leptin levels were higher in
      children with obesity. Area under the ROC curve for WHr-obese (0.77) was higher
      compared to BMI (0.47) and WC (0.48) to detect the CV outcome, P = 0.0006. WHr
      obesity was associated with 5.72 increased odds of having the adverse CV outcome,
      P = 0.0001, while BMI and WC were not significant. CONCLUSION: WHr is more
      sensitive than BMI or WC to detect subclinical CV risk and should be included in
      screening of pediatric kidney transplant recipients.

PMID- 30294897
TI  - The risk of venous thromboembolism during and after hospitalisation in patients
      with inflammatory bowel disease activity.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) increases the risk of venous
      thromboembolism. AIMS: To determine when patients are at high risk of
      thromboembolic events, including after major surgery, and to guide timing of
      thromboprophylaxis. METHODS: Each IBD patient from Clinical Practice Research
      Datalink, linked with Hospital Episode Statistics, was matched to up to five non
      IBD patients in this cohort study. We examined their risk of thromboembolism in
      hospital and within 6 weeks after leaving hospital, with or without undergoing
      major surgery, and while ambulant. Hazard ratios were estimated using Cox
      regression, with adjustment for age, sex, body mass index, smoking and history of
      malignancy or thromboembolism. RESULTS: Overall 23 046 IBD patients had a
      thromboembolic risk 1.74-times (95% CI = 1.55-1.96) higher than 106 795 non-IBD
      patients. Among ambulant patients, the thromboembolic risk was raised during
      acute (hazard ratio = 3.94, 2.79-5.57) or chronic disease activity (3.97, 2.90
      5.45) but their absolute risk remained below 5/1000 person-years. The hazard
      ratio for thromboembolism among in-patients not undergoing major surgery was 1.13
      (0.63-2.02), compared to 2.43 (1.20-4.92) among surgical patients, with a near
      doubling of absolute risk associated with surgery (59.5/1000 person-years,
      compared with 31.1 without surgery). The absolute risk remained elevated within 6
      weeks after leaving hospital (18.6/1000 person-years in IBD patients after
      surgery). CONCLUSIONS: IBD patients are at an increased risk of venous
      thromboembolism. Absolute risks are raised during active disease, when in
      hospital, and after leaving hospital following major surgery.

PMID- 30294898
TI  - Direct Measurement of Electronic Band Structure in Single Quantum Dots of Metal
      Chalcogenide Composites.
AB  - Metal chalcogenide quantum dots (QDs) are among the most promising materials as
      light harvesters in all-inorganic systems for applications in solar cells and
      production of solar fuels. The electronic band structure of composite QDs formed
      by lead and cadmium chalcogenides directly grafted on highly oriented pyrolytic
      graphite surfaces through successive ionic layer absorption and reaction is
      investigated. Atomic force microscopy and Kelvin probe force microscopy (KPFM)
      are applied to investigate PbS, CdS, and PbS/CdS QD systems. The variation of the
      surface potential of individual QDs is measured, investigating the evolution of
      the electronic band structure as a function of QD size and composition. A shift
      of the Fermi level toward more negative values occurs when QD size is increased.
      The shift is more pronounced in CdS than in PbS, while the composite PbS/CdS
      exhibits an intermediate behavior. The calculated shift is in good agreement with
      the experiments. These results highlight the ability of KPFM to directly measure
      the electronic band structure in individual QDs of metal chalcogenide composites.
      This feature regulates charge dynamics in composite systems, thereby affecting
      device performance. This work provides valuable insights for applications in
      several fields, in which charge injection plays a major role.

PMID- 30294899
TI  - Discovery of Elusive K4 O6 , a Compound Stabilized by Configurational Entropy of
      Polarons.
AB  - Synthesis of elusive K4 O6 has disclosed implications of crucial relevance for
      new solid materials discovery. K4 O6 forms in equilibrium from K2 O2 and KO2 , in
      an all-solid state, endothermic reaction at elevated temperature, undergoing back
      reaction upon cooling to ambient conditions. This tells that the compound is
      stabilized by entropy alone. Analyzing possible entropic contributions reveals
      that the configurational entropy of "localized" electrons, i.e., of polaronic
      quasi-particles, provides the essential contribution to the stabilization. We
      corroborate this assumption by measuring the relevant heats of transformation and
      tracking the origin of entropy of formation computationally. These findings
      challenge current experimental and computational approaches towards exploring
      chemical systems for new materials by searching the potential energy landscape:
      one would fail in detecting candidates that are crucially stabilized by the
      configurational entropy of localized polarons.

PMID- 30294900
TI  - Hydrogen sulfide suppresses ghrelin secretion in vitro and delays postprandial
      ghrelin secretion while reducing appetite in mice.
AB  - Ghrelin is a stomach-derived hormone that regulates several metabolic functions
      including growth hormone release, appetite, adiposity, and gastric motility.
      Nutrients, the autonomic nervous system, and other metabolic hormones have all
      been implicated in the regulation of ghrelin secretion. Despite this, ongoing
      efforts to develop modulators of ghrelin secretion in human diseases are still
      underway. Hydrogen sulfide (H2 S) is a gaseous signaling molecule that is
      produced both endogenously in many tissues and by the gut microbiome. H2 S has
      established roles in cardiovascular and immune health, however, more recently H2
      S has been implicated in the regulation of metabolic hormone secretion. We
      hypothesized that H2 S is able to directly regulate ghrelin secretion and in
      turn, regulate appetite. We first demonstrated that GYY4137 (an H2 S donor
      molecule) directly suppresses ghrelin secretion in rat primary gastric culture,
      in part through the activation of the protein kinase B (AKT) pathway. We then
      demonstrated the colocalization of ghrelin-positive gastric cells with the H2 S
      producing enzyme cystathionine-gamma-lyase (CSE). While GYY4137 suppressed
      ghrelin secretion, inhibition of CSE caused a stimulation in ghrelin secretion in
      primary gastric culture. In mice, GYY4137 treatment prolonged the postprandial
      drop of circulating ghrelin and caused reduced food consumption up to 4 h after
      treatment. These results demonstrate for the first time a role for H2 S in the
      regulation of ghrelin and appetite. Modulating H2 S levels may be a novel
      approach to regulate ghrelin secretion in the treatment of metabolic diseases.

PMID- 30294901
TI  - Rapamycin and FK506 derivative TH2849 could ameliorate neurodegenerative diseases
      through autophagy with low immunosuppressive effect.
AB  - Autophagy is an essential cellular process concern with cellular homeostasis down
      regulated by mTOR, whose activity can be modulated by rapamycin, a kind of
      lipophilic macrolide antibiotic, through forming a complex with immunophilin
      FKBP12 essential for mTOR regulation to induce autophagy. Therefore, rapamycin is
      normally used as a neuron protective agent. The immunophilin FKBP12 binding
      ligand FK506 is well known as an immunosuppressive agent by inhibiting the
      calcineurin expression. In this study, we synthesized a series of modified
      compounds based on the FKBP12 binding moiety to as same as the binding structure
      of rapamycin and FK506 particularly. We removed the other binding regions of the
      complex that has the property of immunosuppression. We found that a novel small
      molecule named TH2849 from these derivative compounds has a significant binding
      connection with mTOR by comparing to calcineurin. The effects of TH2849 on
      calcineurin/NFAT were not as significant as FK506, and weak effects on
      IL2/p34cdc2 /cyclin signaling pathway were also found. Moreover, TH2849 also
      shows mitochondrial protective effect through stabilizing the mitochondrial
      structure and transmembrane potential (DeltaPsim) and could rescue dopaminergic
      neurons in MPTP-treated zebrafishes as well as mice models with less
      immunosuppressive effect. Our present study shows that TH2849 works as a
      neuroprotective agent possibly by inducing autophagy and low immunosuppressive
      effect.

PMID- 30294902
TI  - A comparison of the influence of three different lumbar interbody fusion
      approaches on stress in the pedicle screw fixation system: Finite element static
      and vibration analyses.
AB  - This study aimed to examine breakage risk of the bilateral pedicle screw (BPS)
      fixation system under static and vibration loadings after three different types
      of lumbar interbody fusion surgery. A previously validated intact L1-sacrum
      finite element model was modified to simulate anterior, posterior, and
      transforaminal lumbar interbody fusion (ALIF, PLIF, and TLIF, respectively) with
      BPS fixation system (consisting of pedicle screws and rigid connecting rods) at
      L4-L5. As a risk parameter for breakage, the von Mises stresses in the pedicle
      screws and the rods for the ALIF, PLIF, and TLIF models under static loading
      (flexion, extension, lateral bending, and axial torsion moments) and vibration
      loading (sinusoidal vertical load) were calculated and compared. The calculated
      von Mises stresses were different in the ALIF, PLIF, and TLIF models, but these
      stresses for all the fusion models were found to be concentrated in neck of the
      pedicle screw and middle of the rod under both the static and vibration loadings.
      The results from static analyses showed that the maximum stress in the BPS
      fixation system was greater in the TLIF model than in the ALIF and PLIF models
      under all the applied static loadings. The results from transient dynamic
      analyses also showed that the TLIF generated greater dynamic responses of the
      stress in the BPS fixation system to the vertical vibration compared with the
      ALIF and PLIF. It implies that the TLIF procedure might incur a higher risk of
      breakage for the BPS fixation system than the ALIF and PLIF procedures.

PMID- 30294903
TI  - Efficacy of interventions led by staff with geriatrics expertise in reducing
      hospitalisation in nursing home residents: A systematic review.
AB  - OBJECTIVE: To determine the efficacy of interventions, delivered by geriatrics
      trained staff for nursing home residents, in reducing hospitalisation. METHODS:
      Multiple databases and clinical trial registers were searched. Studies that
      provided comparative data and involved residents aged >=65 years evaluating
      patient-level interventions delivered by geriatrics-trained staff were included.
      The systematic review protocol was made available on PROSPERO (registration
      number CRD42017079928; www.crd.york.ac.uk/PROSPERO). RESULTS: Sixteen studies
      were included; six were randomised controlled trials. Studies were categorised
      according to intervention approaches into the following: (i) hospital prevention
      program; (ii) emergency department-based hospital avoidance program; and (iii)
      post-hospital supported discharge program. The Grading of Recommendations,
      Assessment, Development and Evaluation (GRADE) quality of evidence was low to
      moderate. Most studies demonstrated a favourable trend; however, only a few
      reported statistically significant reductions in hospitalisations. Results from
      the randomised studies were non-significant. CONCLUSIONS: Despite the
      heterogeneity of studies, there is limited evidence that interventions delivered
      by geriatrics-trained staff reduce hospitalisations in nursing home residents.
      Further work examining decision-making around hospital transfer may help inform
      future intervention design.

PMID- 30294904
TI  - Bone marrow mesenchymal stem cells stimulated with low-intensity pulsed
      ultrasound: Better choice of transplantation treatment for spinal cord injury:
      Treatment for SCI by LIPUS-BMSCs transplantation.
AB  - Stem cell transplantation, especially treatment with bone marrow mesenchymal stem
      cells (BMSCs), has been considered a promising therapy for the locomotor and
      neurological recovery of spinal cord injury (SCI) patients. However, the clinical
      benefits of BMSCs transplantation remain limited because of the considerably low
      viability and inhibitory microenvironment. In our research, low-intensity pulsed
      ultrasound (LIPUS), which has been widely applied to clinical applications and
      fundamental research, was employed to improve the properties of BMSCs. The most
      suitable intensity of LIPUS stimulation was determined. Furthermore, the
      optimized BMSCs were transplanted into the epicenter of injured spinal cord in
      rats, which were randomized into four groups: (a) Sham group (n = 10), rats
      received laminectomy only and the spinal cord remained intact. (b) Injury group
      (n = 10), rats with contused spinal cord subjected to the microinjection of PBS
      solution. (c) BMSCs transplantation group (n = 10), rats with contused spinal
      cord were injected with BMSCs without any priming. (d) LIPUS-BMSCs
      transplantation group (n = 10), BMSCs stimulated with LIPUS were injected at the
      injured epicenter after contusion. Rats were then subjected to behavioral tests,
      immunohistochemistry, and histological observation. It was found that BMSCs
      stimulated with LIPUS obtained higher cell viability, migration, and neurotrophic
      factors expression in vitro. The rate of apoptosis remained constant. After
      transplantation of BMSCs and LIPUS-BMSCs postinjury, locomotor function was
      significantly improved in LIPUS-BMSCs transplantation group with higher level of
      brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the
      epicenter, and the expression of neurotrophic receptor was also enhanced.
      Histological observation demonstrated reduced cavity formation in LIPUS-BMSCs
      transplantation group when comparing with other groups. The results suggested
      LIPUS can improve BMSCs viability and neurotrophic factors expression in vitro,
      and transplantation of LIPUS-BMSCs could promote better functional recovery,
      indicating possible clinical application for the treatment of SCI.

PMID- 30294905
TI  - Alteration of serum and tissue tumor necrosis factor alpha levels: A possible
      mechanism of action of oral pulse steroids in the treatment of alopecia areata.
AB  - BACKGROUND: Alopecia areata (AA) is a multifactorial disease in which tumor
      necrosis factor alpha (TNF-alpha) plays an important role. OBJECTIVE: To study
      the effect of oral pulse steroids on both serum and tissue levels of TNF-alpha in
      AA patients. METHODS: Skin biopsies and serum samples were collected from 20
      patients with patchy AA before and after treatment (oral prednisolone for two
      consecutive days every week for 3 months) for determination of the levels of TNF
      alpha levels using ELISA technique. RESULTS: Both serum and tissue levels of TNF
      alpha in AA patients were significantly higher than in controls before (P <
      0.001) as well as after treatment (P = 0.0169 and P = 0.3051), respectively. The
      duration of disease negatively correlated with tissue TNF-alpha before treatment
      (P < 0.0001). Serum and tissue levels of TNF-alpha dropped significantly after
      treatment (P < 0.0001). The percentage of reduction of both tissue and serum TNF
      alpha levels correlated positively with the percentage of clinical improvement (r
      = 0.682, P = 0.0009; r = 0.567, P = 0.009, respectively). CONCLUSION: TNF-alpha
      plays an important role in the evolution of AA lesions, and alteration in both
      serum and tissue levels of TNF-alpha could be considered one of the important
      mechanisms of action of systemic oral pulse steroids in the treatment of AA.

PMID- 30294907
TI  - Sentinel lymph node biopsy remains the most accurate method of obtaining staging
      and prognostic information for patients with primary cutaneous melanomas.

PMID- 30294906
TI  - N-acetylcysteine targets 5 lipoxygenase-derived, toxic lipids and can synergize
      with prostaglandin E2 to inhibit ferroptosis and improve outcomes following
      hemorrhagic stroke in mice.
AB  - OBJECTIVES: N-acetylcysteine (NAC) is a clinically approved thiol-containing
      redox modulatory compound currently in trials for many neurological and
      psychiatric disorders. Although generically labeled as an "antioxidant," poor
      understanding of its site(s) of action is a barrier to its use in neurological
      practice. Here, we examined the efficacy and mechanism of action of NAC in rodent
      models of hemorrhagic stroke. METHODS: Hemin was used to model ferroptosis and
      hemorrhagic stroke in cultured neurons. Striatal infusion of collagenase was used
      to model intracerebral hemorrhage (ICH) in mice and rats. Chemical biology,
      targeted lipidomics, arachidonate 5-lipoxygenase (ALOX5) knockout mice, and viral
      gene transfer were used to gain insight into the pharmacological targets and
      mechanism of action of NAC. RESULTS: NAC prevented hemin-induced ferroptosis by
      neutralizing toxic lipids generated by arachidonate-dependent ALOX5 activity. NAC
      efficacy required increases in glutathione and is correlated with suppression of
      reactive lipids by glutathione-dependent enzymes such as glutathione S
      transferase. Accordingly, its protective effects were mimicked by chemical or
      molecular lipid peroxidation inhibitors. NAC delivered postinjury reduced
      neuronal death and improved functional recovery at least 7 days following ICH in
      mice and can synergize with clinically approved prostaglandin E2 (PGE2 ).
      INTERPRETATION: NAC is a promising, protective therapy for ICH, which acted to
      inhibit toxic arachidonic acid products of nuclear ALOX5 that synergized with
      exogenously delivered protective PGE2 in vitro and in vivo. The findings provide
      novel insight into a target for NAC, beyond the generic characterization as an
      antioxidant, resulting in neuroprotection and offer a feasible combinatorial
      strategy to optimize efficacy and safety in dosing of NAC for treatment of
      neurological disorders involving ferroptosis such as ICH. Ann Neurol 2018;00:1
      19.

PMID- 30294908
TI  - Anticoagulant rodenticide toxicosis causing tracheal collapse in 4 small breed
      dogs.
AB  - OBJECTIVE: To describe 4 cases of tracheal narrowing attributed to tracheal
      mucosal hemorrhage caused by anticoagulant rodenticide toxicity in breeds
      predisposed to tracheal collapse. CASE SUMMARY: Over the years 2005-2014, 4 dogs
      were presented for respiratory distress secondary to diffuse tracheal narrowing.
      All dogs had possible anticoagulant rodenticide ingestion and prolonged
      prothrombin time. All dogs received fresh-frozen plasma transfusions, vitamin K1
      supplementation, and supportive care. Tracheal narrowing improved on follow-up
      radiographs in 3 of 4 patients. One of 4 did not have follow-up radiographs
      performed. All dogs survived. NEW OR UNIQUE INFORMATION PROVIDED: Anticoagulant
      rodenticide toxicity causing clinical signs consistent with tracheal collapse is
      a rare but recognized phenomenon that has not been previously reported in breeds
      prone to tracheal collapse.

PMID- 30294909
TI  - Vertebral column deformity in adult wild haddock (Melanogrammus aeglefinus).
AB  - This study describes radiological malformations in the vertebral column of adult
      sexually mature wild haddock, Melanogrammus aeglefinus collected from Masfjorden,
      Western Norway, in 2014 and 2015. There were seven deformed fish (33% of sampled
      fish), five with mild deformities and two with severe deformities. The deformity
      types discovered were lordosis, vertebra body asymmetry, compression, fusion
      (ankylosis), remodelling, and haemal spine hyperostosis. The two severely
      deformed fish were as follows: (a) one specimen with 29 deformed vertebrae within
      the region vertebrae nos. 1-30, including two sites of lordosis; (b) one specimen
      with 15 deformed vertebrae within the region vertebrae nos. 31-52 (most caudal
      vertebrae). The results of this study show that wild haddock can survive severe
      vertebra deformities, both in the trunk and tail region, and reach adulthood and
      sexual maturity. Whether normal nondeformed wild conspecifics would mate and
      spawn with these individuals and thereby complete the life cycle of the deformed
      individuals is, however, unknown. A possible link between bone fracture and fish
      hyperostosis is discussed.

PMID- 30294910
TI  - Cardiovascular disease and other childhood-onset chronic conditions in adults
      with cerebral palsy.

PMID- 30294911
TI  - CD36 is indispensable for nutrient homeostasis and endurance exercise capacity
      during prolonged fasting.
AB  - During fasting, most tissues including skeletal muscle heavily rely on
      utilization of fatty acids (FA) and minimize glucose use. In contrast, skeletal
      muscle prefers carbohydrate use as exercise intensity increases. In mice
      deficient for CD36 (CD36-/- mice), FA uptake is markedly reduced with a
      compensatory increase in glucose uptake in skeletal muscle even during fasting.
      In this study, we questioned how exercise endurance is affected during prolonged
      fasting in CD36-/- mice where glucose utilization is constantly increased. With
      or without a 24-h fast, a single bout of treadmill exercise was started at the
      speed of 10 m/min, and the speed was progressively increased up to 30 m/min until
      mice were exhausted. Running distance of wild type (WT) and CD36-/- mice was
      comparable in the fed state whereas that of CD36-/- mice was significantly
      reduced after a 24-h fast. Glycogen levels in liver and skeletal muscle were
      depleted both in WT and CD36-/- mice after a 24-h fast. In CD36-/- mice, FA
      uptake by skeletal muscle continued to be reduced during fasting. Glucose
      utilization also continued to be enhanced in the heart and oxidative skeletal
      muscle and glucose supply relative to its demand was diminished, resulting in
      accelerated hypoglycemia. Consequently, available energy substrates from serum
      and in muscle for exercise performance were very limited in CD36-/- mice during
      prolonged fasting, which could cause a remarkable reduction in exercise
      endurance. In conclusion, our study underscores the importance of CD36 for
      nutrient homeostasis to maintain exercise performance of skeletal muscle when
      nutrient supply is limited.

PMID- 30294912
TI  - Microbial contamination in methanol biofilters inoculated with a pure strain of
      Pichia pastoris: A potential limitation for waste revalorization.
AB  - Novel biotechnologies to valorize waste emissions are based on the use of
      specialized microbial groups that produce different compounds of industrial
      interest. On this scenario, the retention of such specific microorganisms in the
      system is of critical interest; however, the potential limitations of working
      with simplified cultures in a competitive open environment are neither fully
      explored nor well understood. In this work, a series of biofilters treating
      methanol vapors coupled with heterologous endochitinase production were used to
      evaluate the performance of a specialized microbial population during a typical
      open-to-environment operation. The biofilters were inoculated with a transformed
      strain of Pichia pastoris and were operated identically for about 90 days. The
      results showed that the biofiltration performance became diverse with time in
      terms of the elimination capacity (EC) shifting from a variation coefficient of
      1.5% (EC = 274 +/- 24, 279 +/- 5, and 281.9 +/- 25 g/[m3 h]) at the beginning of
      the operation to 33% (EC = 297 +/- 9, 338 +/- 7, and 341 +/- 2 g/[m3 h]) at the
      end of operation. Epifluorescence analysis and cloning-sequencing suggested that
      P. pastoris remained as the dominant microorganism of methanol degradation,
      whereas diverse airborne bacteria, including Ochrobactrum spp. and Klebsiella
      oxytoca, played a secondary role possibly associated with the consumption of
      intermediates. Overall, this study found that low diversity systems operated
      under non-sterile conditions could be susceptible to contamination with external
      microorganisms causing a diversifying behavior at the performance and microbial
      community levels. (c) 2018 American Institute of Chemical Engineers Biotechnol.
      Prog., 2018.

PMID- 30294913
TI  - The long non-coding RNA MALAT1 promotes ovarian cancer progression by regulating
      RBFOX2-mediated alternative splicing.
AB  - Ovarian cancer metastasizes via direct seeding, whereby cancer cells shed from
      the primary site, resist cell death in the peritoneal cavity, then metastasize to
      peritoneal organs. We sought to identify molecular mechanisms that facilitate
      ovarian cancer cell anchorage independent survival. Gene expression profiling was
      performed on ovarian cancer cells grown in attached or forced suspension culture
      and confirmed by RT-qPCR. Anoikis was measured by Caspase 3/7 assay. Since the
      long non-coding RNA Metastasis Associated Lung Adenocarcinoma transcript 1
      (MALAT1) was among the transcripts most highly increased in forced suspension
      culture, modified anti-sense oligonucleotides (ASO) were used to inhibit its
      expression. Knockdown of RBFOX2 and KIF1B was performed using shRNAs. Publically
      available datasets were analyzed for association of MALAT1 gene expression with
      clinicopathological variables. In multiple anoikis-resistant ovarian cancer cell
      lines MALAT1 expression increased after 24 and 48 h in forced suspension culture
      compared to attached culture. High MALAT1 is associated with increased stage,
      recurrence, and reduced survival in ovarian cancer, and in a small percentage of
      ovarian cancers MALAT1 is amplified. MALAT1 knockdown resulted in decreased
      proliferation, invasion, anchorage-independent growth, and increased anoikis.
      Suppression of MALAT1 also resulted in decreased expression of RBFOX2, and
      alternative processing of the pro-apoptotic tumor suppressor gene KIF1B. RBFOX2
      suppression resulted in preferential splicing of the pro-apoptotic isoform of
      KIF1B (KIFB1B-beta) and increased anoikis. The lncRNA MALAT1 facilitates a pro
      metastatic phenotype in ovarian cancer by promoting alternative RNA processing
      and differential expression of anti-apoptosis and epithelial to mesenchymal
      transition (EMT)-related genes.

PMID- 30294914
TI  - A role for surgery in the treatment of relapsed Hodgkin lymphoma.
AB  - Treatment of Hodgkin lymphoma (HL) has advanced over time, rendering a fatal
      disease now largely curable. Multiagent chemotherapy regimens, hematopoietic stem
      cell transplantation, and radiotherapy are the mainstays of care. Surgical
      intervention is rarely indicated other than for biopsy at diagnosis. However, for
      patients with recurrent relapsed HL isolated to one anatomical location,
      refractory to all other therapy, there may be a beneficial role for surgical
      excision. Herein, we report the surgical management of three relapsed patients
      with stage IVB HL who were refractory to multiple other therapeutic approaches,
      who all achieved good event-free survival after operative management.

PMID- 30294915
TI  - Hedgehog-Like Gold-Coated Magnetic Microspheres that Strongly Inhibit Tumor
      Growth through Magnetomechanical Force and Photothermal Effects.
AB  - Using magnetomechanical force to kill cancer cells has attracted great attention
      recently. This study presents novel hedgehog-like microspheres composed of needle
      like magnetic nanoparticles with carbon and gold double shells. Using a novel low
      frequency vibrating magnetic field (VMF), these microspheres with sharp surfaces
      can seriously damage cancer cells and strongly inhibit mouse tumor growth through
      mechanical force. The cell killing efficiency depends on VMF exposure time,
      frequency, strength, and microsphere concentration. The maximum mechanical force
      generated by one microsphere acting on a cancer cell under a VMF is about 35.79
      pN. The microspheres also induce photothermal ablation after being triggered by
      near-infrared laser irradiation. Mouse tumors could not be detected after
      treatment with the synergistic stimuli of mechanical force and photothermal
      ablation. These results reveal a simple and highly efficient strategy using
      magnetic microspheres for local treatment of solid tumors in a remote and
      noninvasive manner.

PMID- 30294916
TI  - Chinese Oak Tasar Silkworm Antheraea pernyi Silk Proteins: Current Strategies and
      Future Perspectives for Biomedical Applications.
AB  - Chinese nonmulberry temperate oak tasar/tussah, Antheraea pernyi (Ap) silk is a
      natural biopolymer that has attracted considerable attention as a biomaterial.
      The proteinaceous components of Ap silk proteins, namely fibroin and sericin may
      represent an alternative over mulberry Bombyx mori silk proteins. In fact, the
      silk fibroin (SF) of Ap is rich in Arginyl-Glycyl-Aspartic acid (RGD) peptides,
      which facilitate the adhesion and proliferation of various cell types. The
      possibility of processing Ap silk proteins into different distinct 2D- and 3D
      based matrices is described in earlier studies, such as membranes, nanofibers,
      scaffolds, and micro/nanoparticles, contributing to a different rate of
      degradation, mechanical properties, and biological performance useful for various
      biomedical applications. This review summarizes the current advances and
      developments on nonmulberry Chinese oak tasar silk protein (fibroin and sericin)
      based biomaterials and their potential uses in tissue engineering, regenerative
      medicine, and therapeutic delivery strategies.

PMID- 30294917
TI  - A survey of the treatment and management of patients with severe chronic
      spontaneous urticaria.

PMID- 30294918
TI  - Radiological changes during fracture and repair in neural and haemal spines of
      Atlantic cod (Gadus morhua).
AB  - Although spinal injuries in fish have been associated with electric stimuli
      applied during electrofishing and electrotrawling, bone fracture and repair in
      the axial skeleton have yet not been studied. To study this, we radiographed a
      group (n = 64) of individually tagged farmed cod twice, with a 1-year interval
      (~36 cm at first and ~ 50 cm at second inspection). The study focus was on the
      neural and haemal spines. These structures are un-paired and are not covered by
      other bones laterally, making them useful for radiological studies on axial
      skeletal fracture in live fish. At the first examination, four animals showed
      radiological changes in their neural and haemal spines. Two animals had
      fractures, and two had callus formations. One year later, at the second
      radiological examination, the fractures had developed into calluses or into
      normal morphology, and calluses either remained as calluses or had developed into
      normal morphology. A further 14 animals that were all normal at the first
      inspection had developed changes in their neural and haemal spines, both
      fractures and callus formations. This is the first record of spontaneous bone
      fracture in fish; the fractures observed occurred under normal farming conditions
      and were not induced. The results show that cod have a functional fracture
      healing mechanism in their neural and haemal spines. The findings are discussed
      in relation to fish hyperostosis.

PMID- 30294919
TI  - Can Living Transplant Donors Refuse Blood Transfusion? Case Reports of Living
      Kidney Transplantation From Jehovah's Witnesses.

PMID- 30294920
TI  - Vito Pistoia (1949-2018).

PMID- 30294921
TI  - Primary cutaneous lymphoma in Argentina: a report of a nationwide study of 416
      patients.
AB  - BACKGROUND: The aim of this study was to determine the relative frequency of
      primary cutaneous lymphoma (PCL) in Argentina according to the new World Health
      Organization (WHO)-European Organization for the Research and Treatment of Cancer
      (EORTC) classification system. METHODS: A total of 416 patients from 21
      dermatology services were included during a 5-year period (2010-2015); these
      patients were classified using WHO-EORTC criteria. RESULTS: There were 231
      (55.2%) males and 185 (44.8%) females; the male-to-female ratio was 1.35. The
      median age of the patients was 57 years (range, 0-90 years). Most patients were
      Caucasian (79%), and only 16% of patients were registered as Amerindian. Most
      patients (387/416, 93%) had cutaneous T-cell lymphoma (CTCL); 28 patients (6.7%)
      were diagnosed with cutaneous B-cell lymphoma (CBCL). The most frequent CTCL
      subtypes, in decreasing order of prevalence, were mycosis fungoides (MF),
      including its variants (75.7%); CD30+ primary cutaneous lymphoproliferative
      disorders (7.2%); and Sezary syndrome (SS) (3.1%). Cutaneous follicle center
      lymphoma was the most common CBCL subtype (2.9%). In the subset of patients <=20
      years of age, the most common condition was MF (57%), followed by extranodal NK-T
      nasal-type lymphoma (14%). CONCLUSIONS: This study revealed relatively higher
      rates of MF and lower rates of CBCL in Argentinean patients that have been
      reported in American and European countries.

PMID- 30294922
TI  - Re-Evaluating the Assistant Practitioner Role in NHS England: Survey Findings.
AB  - AIM AND BACKGROUND: In the absence of data providing an overview on the state of
      the assistant practitioner (AP) workforce, this study surveys trusts in NHS
      England with the aim of establishing how the role is viewed, used and managed.
      METHODS: Based on an earlier survey undertaken around a decade ago, an online
      questionnaire was sent to members of an assistant practitioner network,
      generating a response from over fifty different trusts, drawn from different
      regions and healthcare settings. RESULTS: The survey results highlight the
      increased use of assistant practitioners by trusts and in a more diverse range of
      clinical settings. This increase has been driven more by the apparent value of
      the APs in addressing issues of service design and quality, than by attempts to
      reduce costs through substitution and skill mix dilution. CONCLUSIONS: The AP
      role has retained value to nurse managers in developing and designing services,
      and indeed in establishing a career pathway for healthcare assistants. Most
      striking are future intentions to continue using APs, particularly within the
      context of the emerging nursing associate (NA) role. This suggests that the AP
      and NA are likely to be complementary rather than alternative roles. IMPLICATIONS
      FOR NURSING MANAGERS: Nurse managers might note the continuing use and value of
      the AP role, although as means of improving design and quality as well as
      providing career opportunities for healthcare assistants, rather than as a way of
      saving labour costs. Clearly the AP role has a future although there is scope to
      review its position in relation to the newly emerging nurse associate role. This
      article is protected by copyright. All rights reserved.

PMID- 30294924
TI  - Prevalence and clinical characteristics of refractoriness to optimal proton pump
      inhibitor therapy in non-erosive reflux disease.
AB  - BACKGROUND: The real size of the gastro-oesophageal reflux disease (GERD)
      population not responding to proton pump inhibitor (PPI) therapy has still not
      been fully elucidated. Causes of PPI refractoriness include incorrect diagnosis
      and lack of adherence to therapy, in terms of incorrect dosage and timing. AIMS:
      To evaluate the prevalence of refractoriness to optimal PPI therapy and the
      contribution of non-erosive reflux disease (NERD), reflux hypersensitivity, and
      functional heartburn, to PPI refractoriness. The association of functional GI
      symptoms in non-responders was evaluated. METHODS: Frequency and severity of GERD
      symptoms (heartburn, regurgitation, chest pain), dysphagia, belching, epigastric
      pain, postprandial distress, irritable bowel syndrome (IBS), globus, and ear nose
      and throat (ENT) symptoms were evaluated in patients previously classified as non
      responders. Patients with at least one of the oesophageal symptoms with a
      frequency >=3 /week were treated with esomeprazole 40 mg once daily for 8 weeks
      and then re-evaluated. Non-responders (patients with oesophageal symptoms >=3
      times per week) underwent 24 hour multichannel intraluminal impedance-pH
      monitoring. RESULTS: Of 573 consecutive patients, 92 with oesophageal symptoms
      and classified as PPI-refractory underwent the esomeprazole trial; 60 did not
      respond. IBS, epigastric pain, and post-prandial distress episodes were
      associated with a poor response on multivariate analysis. NERD, reflux
      hypersensitivity, and functional heartburn patients constituted 32%, 42%, and
      26%, respectively of the PPI-refractory group. CONCLUSIONS: True refractoriness
      in patients with GERD symptoms attending a secondary care setting is lower than
      previously reported. Following a careful history and optimal PPI dosing, the rate
      of refractoriness was 20%. True NERD constitutes only a third of the PPI
      refractory group.

PMID- 30294925
TI  - Increased risk of mycotic infections associated with sodium-glucose co
      transporter 2 inhibitors: a prescription sequence symmetry analysis.
AB  - AIMS: To determine the risk of mycotic infections associated with the use of
      sodium-glucose co-transporter 2 inhibitors (SGLT2i) in a real-world setting.
      METHODS: We conducted a prescription sequence symmetry analysis using data from
      Truven Health MarketScan (2009-2015). We selected continuously enrolled patients
      newly initiating both an SGLT2i and an antifungal between 1 April 2013 and 31
      December 2015 within time periods of 30, 60, 90, 180 or 365 days of each other.
      Adjusted sequence ratios (ASR) were calculated for each time period as the ratio
      of patients initiating SGLT2i first over those initiating an antifungal first
      adjusted for time trends in prescribing. Analyses were stratified by sex and type
      of SGLT2i. RESULTS: There were 23 276 patients who newly initiated both SGLT2i
      and an antifungal in our study period. These patients were further classified
      into those initiating the two drugs within 365 (n = 17 504), 180 (n = 11 873), 90
      (n = 7697), 60 (n = 5856) or 30 (n = 3650) days of each other. Increased risks of
      mycotic infections were present across all time periods, with the strongest
      effect observed in the 90-day interval [ASR 1.53 (confidence interval, CI 1.43
      1.60)]. Findings differed by sex [90-day ASR females: 1.65 (CI 1.56-1.74); males
      1.25 (CI 1.14-1.36)] and by SGLT2i [90-day ASR canagliflozin 1.57 (CI 1.49-1.66);
      non-canagliflozin 1.42 (CI 1.31-1.55)]. CONCLUSION: Initiation of SGLT2i was
      associated with an increased risk for mycotic infections. Findings from this
      commercially insured population in the real world are consistent with evidence
      available from clinical trials.

PMID- 30294923
TI  - Mitochondrial dysfunction and increased glycolysis in prodromal and early
      Parkinson's blood cells.
AB  - BACKGROUND: Although primarily a neurodegenerative process, there is increasing
      awareness of peripheral disease mechanisms in Parkinson's disease. To investigate
      disease processes in accessible patient cells, we studied peripheral blood
      mononuclear cells in recently diagnosed PD patients and rapid eye movement-sleep
      behavior disorder patients who have a greatly increased risk of developing PD. We
      hypothesized that peripheral blood mononuclear cells may recapitulate cellular
      pathology found in the PD brain and investigated these cells for mitochondrial
      dysfunction and oxidative stress. METHODS: Peripheral blood mononuclear cells
      were isolated and studied from PD patients, rapid eye movement-sleep behavior
      disorder patients and age- and sex-matched control individuals from the well
      characterized Oxford Discovery cohort. All participants underwent thorough
      clinical assessment. RESULTS: Initial characterization showed that PD patients
      had elevated levels of CD14 + monocytes and monocytes expressing C-C motif
      chemokine receptor 2. Mitochondrial dysfunction and oxidative stress were
      increased in PD patient peripheral blood mononuclear cells, with elevated levels
      of mitochondrial reactive oxygen species specifically in patient monocytes. This
      was combined with reduced levels of the antioxidant superoxide dismutase in blood
      cells from PD patients and, importantly, also in rapid eye movement-sleep
      behavior disorder patients. This mitochondrial dysfunction was associated with a
      concomitant increase in glycolysis in both PD and rapid eye movement-sleep
      behavior disorder patient blood cells independent of glucose uptake or monocyte
      activation. CONCLUSIONS: This work demonstrates functional bioenergetic deficits
      in PD and rapid eye movement-sleep behavior disorder patient blood cells during
      the early stages of human disease. (c) 2018 The Authors. Movement Disorders
      published by Wiley Periodicals, Inc. on behalf of International Parkinson and
      Movement Disorder Society.

PMID- 30294926
TI  - Fresh thoughts and perspectives on CARES study from viewpoint of an Asian
      physician: comment on the article by Choi et al.
AB  - Following the report of CARES study published on NEJM and associated U.S. FDA's
      safety alert concerning febuxostat for management of hyperuricemia in gout, Choi
      et al. provided a timely and insightful evaluation on CARES study, which well
      covered the significance of the trial, strength of the design, concerns on high
      discontinuation rate and so on. As a major urate-lowering therapy (ULT) drug
      which was used worldwide, release of CARES results and FDA alert had a profound
      impact on the society of gout and patient communities. This article is protected
      by copyright. All rights reserved.

PMID- 30294927
TI  - Co-administration of nuciferine reduces the concentration of metformin in liver
      via differential inhibition of hepatic drug transporter OCT1 and MATE1.
AB  - Nuciferine (NF), one of the main and effective components in Nelumbo nucifera
      Gaertn. leaf extracts, is a promising drug candidate for the treatment of obesity
      related diseases, while metformin is a first line therapeutic drug for type 2
      diabetes mellitus. Since nuciferine and metformin are likely to be co
      administered, the aim of the present study was to evaluate whether co
      administration of nuciferine would influence the liver (target tissue)
      distribution and the anti-diabetic effect of metformin by inhibiting hepatic
      organic cation transporter 1 (OCT1) and multidrug and toxin extrusion 1 (MATE1).
      The data demonstrated that nuciferine significantly reduced metformin
      accumulation in MDCK cells stably expressing human OCT1 (MDCK-hOCT1) or hMATE1
      (MDCK-hMATE1), and primary cultured mouse hepatocytes. Furthermore, the presence
      of nuciferine in the basal compartment caused a concentration-dependent reduction
      of intracellular metformin accumulation in MDCK-hOCT1/hMATE1 cell monolayers.
      Compared with the metformin treatment-alone group, co-administration of
      nuciferine (40 mg/kg) markedly reduced the metformin concentration in mouse
      livers at 30 and 60 min after a single oral dose of metformin (200 mg/kg), and
      subsequently impaired the glucose-lowering effect of metformin (200 mg/kg), but
      the glucose-lowering effect became no different at 90 and 120 min. Therefore,
      nuciferine influenced the liver concentration and glucose-lowering effect of
      metformin only for a period of time after dose, administration of nuciferine and
      metformin with an interval might prevent the drug-drug interaction mediated by
      OCT1 and MATE1.

PMID- 30294928
TI  - Using photo-elicitation to explore the lived experience of informal caregivers of
      individuals living with dementia.
AB  - OBJECTIVES: This study aims to explore the subjective lived experience of
      informal caregivers supporting an individual with dementia. DESIGN: This study
      uses the interpretive phenomenological approach utilizing the method of photo
      elicitation and in-depth semi-structured interviews. METHODS: Six individuals
      were given a disposable camera to capture photographs which they felt illustrated
      their own lived experiences of being a caregiver of an individual living with
      dementia. Photographs were printed and used to form discussion within an in-depth
      semi-structured interview. The photographs provided an innovative way of
      capturing the lived experiences of formal dementia caregivers and allowed the
      interview data to be grounded in their daily living, centring around their own
      lived experiences. RESULTS: Three themes emerged from data analysis:
      'conceptualising the role of informal caregiver', 'support for the informal
      caregiver', and 'the caregivers own needs'. CONCLUSIONS: Findings demonstrated
      the complexity of the relationship between the caregiver and the person living
      with dementia, and the shift in this relationship specifically due to the role of
      carer, with notable differences between spousal caregivers and adult-child
      caregivers. The importance of social, emotional, and practical support for
      caregivers was highlighted, as well as significance of the caregiver's individual
      needs. Statement of contribution What is already known on this subject? Informal
      caregivers of individuals living with dementia cover much of the associated
      health care costs. Informal caregiving of individuals living with dementia can
      lead to negative health outcomes of the carer. Health outcomes of informal
      caregivers living with dementia are grounded in culture and are influenced by
      multiple factors. What does this study add? The complexity of the transition from
      family member to informal caregiver has both a physical and emotional impact on
      caregivers. The transition, and experiences of informal caregiving, is dependent
      on the relationship to the individual living with dementia. Caregiver support and
      recognizing the caregiver's individual needs were imperative to caregiver well
      being.

PMID- 30294929
TI  - Bone Marrow Stem Cells-Seeded Polyethylene Terephthalate Scaffold in Repair and
      Regeneration of Rabbit Achilles Tendon.
AB  - The objective of this study was to evaluate the effect of bone marrow stem cells
      (BMSCs)-seeded polyethylene terephthalate (PET) scaffold for Achilles tendon
      repair in a rabbit model. The allogeneic BMSCs were seeded onto the PET scaffold
      and cultured in vitro for 14 days. Sixteen mature New Zealand rabbits underwent
      surgery to establish a 2-cm Achilles tendon defect model. The BMSCs-seeded PET
      scaffold was implanted into the defect of one limb (BMSCs-PET group), while the
      PET scaffold without BMSCs was implanted into the defect of contralateral limb as
      the control (PET group). All rabbits were sacrificed at 6 and 12 weeks after
      surgery. At 12 weeks after surgery, macroscopic and histological results showed
      formation of tendon-like tissues, and the structure was more mature in the BMSCs
      PET group. Immunohistochemical analysis and real-time polymerase chain reaction
      (RT-PCR) demonstrated that the collagen I and collagen III were significantly
      higher in the BMSCs-PET group compared with those in the PET group. Mechanically,
      both the failure load and the average stiffness were significantly higher in the
      BMSCs-PET group than those in the PET group. In conclusion, BMSCs-seeded PET
      scaffold could effectively facilitate the healing process after being implanted
      in a rabbit Achilles tendon defect model.

PMID- 30294930
TI  - Admission 25-Hydroxyvitamin D Levels Are Associated With Functional Status at
      Time of Discharge from Intensive Care Unit in Critically Ill Surgical Patients.
AB  - BACKGROUND: Vitamin D status is associated with length of stay (LOS) and
      discharge destination in critically ill patients. To further understand this
      relationship, we investigated whether admission 25-hydroxyvitaminD (25OHD) levels
      are associated with discharge functional status in the intensive care unit (ICU).
      METHODS: In this retrospective study, data from 2 surgical ICUs at a large
      teaching hospital were analyzed. 25OHD levels were measured within 24 hours of
      ICU admission and Functional Status Score for the ICU (FSS-ICU) was calculated
      within 24 hours of ICU discharge for all patients. To investigate the association
      of vitamin D status with FSS-ICU, we constructed linear and logistic regression
      models, controlling for body mass index, Nutrition Risk in the Critically Ill
      score, ICU LOS, and cumulative protein or caloric deficit during ICU admission.
      RESULTS: Mean 25OHD level and FSS-ICU was 19 (SD 8) ng/mL and 17 (SD 4),
      respectively, in the analytic cohort (n = 300). Each unit increase in 25OHD level
      was associated with a 0.2 increment in FSS-ICU (beta = .20; 95% CI 0.14-0.25).
      Patients with 25OHD levels <20 ng/mL had >3-fold risk of low FSS-ICU (<17)
      compared with patients with 25OHD >20 ng/mL (OR 3.45; 95% CI 1.96-6.08).
      CONCLUSIONS: Our results suggest that vitamin D status at admission is associated
      with discharge FSS-ICU in critically ill surgical patients. Future studies are
      needed to validate our results, to build upon our findings, and to determine
      whether optimizing 25OHD levels can improve functional status and other important
      clinical outcomes in ICU patients.

PMID- 30294931
TI  - Breast implant-associated anaplastic large cell lymphoma with lymph node
      localization: case report and review of literature.

PMID- 30294932
TI  - Modeling the Structure and Dynamics of Semantic Processing.
AB  - The contents and structure of semantic memory have been the focus of much recent
      research, with major advances in the development of distributional models, which
      use word co-occurrence information as a window into the semantics of language. In
      parallel, connectionist modeling has extended our knowledge of the processes
      engaged in semantic activation. However, these two lines of investigation have
      rarely been brought together. Here, we describe a processing model based on
      distributional semantics in which activation spreads throughout a semantic
      network, as dictated by the patterns of semantic similarity between words. We
      show that the activation profile of the network, measured at various time points,
      can successfully account for response times in lexical and semantic decision
      tasks, as well as for subjective concreteness and imageability ratings. We also
      show that the dynamics of the network is predictive of performance in relational
      semantic tasks, such as similarity/relatedness rating. Our results indicate that
      bringing together distributional semantic networks and spreading of activation
      provides a good fit to both automatic lexical processing (as indexed by lexical
      and semantic decisions) as well as more deliberate processing (as indexed by
      ratings), above and beyond what has been reported for previous models that take
      into account only similarity resulting from network structure.

PMID- 30294933
TI  - Acitretin: a promising therapy for localized childhood lichen myxoedematosus.

PMID- 30294934
TI  - What makes a biostatistician?
AB  - Biostatisticians play an important role in medical research. They are co
      responsible for an appropriate and efficient study design, they are involved in
      monitoring the study conduct, they plan and perform the data analysis, and they
      are involved in interpreting and publishing the results. However, how are the
      biostatisticians prepared for their tasks and responsibilities? Graduate programs
      in biostatistics are being offered, but some practicing biostatisticians
      completed their studies in a mathematical or epidemiological program, or obtained
      their degree in subject-specific fields (such as medicine or biology). Therefore,
      the expertise and the competencies can vary widely between the individual
      biostatisticians, also depending on the application field. In this article,
      focusing on European and US practices, we discuss the required professional
      expertise for the main areas of applications in the medical field as well as the
      necessary soft skill competencies of a biostatistician.

PMID- 30294935
TI  - Neuromuscular correlates of motor function in cerebral palsy: towards targeted
      treatment.

PMID- 30294936
TI  - Sporadic case of Darier disease caused by a novel splice-site mutation in the
      ATP2A2 gene.

PMID- 30294937
TI  - Resilience and mental health nursing: An integrative review of international
      literature.
AB  - Mental health nurses work in challenging and potentially high stress settings.
      Stressors can occur in the context of consumer, family, and/or staff
      relationships, as well as the work environment and organization. The cumulative
      effects of stress and professional challenges can lead to harmful impacts for
      mental health nurses including burnout and poorer physical and mental health.
      Resilience involves a process of positive adaptation to stress and adversity. The
      aims of this integrative review were to examine understandings and perspectives
      on resilience, and explore and synthesize the state of knowledge on resilience in
      mental health nursing. Following systematic search processes, screening, and data
      extraction, 12 articles were included. Constant comparative analysis and
      synthesis of the data resulted in two key categories: Theoretical concepts of
      resilience and Knowledge on mental health nurses' resilience. In mental health
      nursing, resilience has been variously constructed as an individual ability,
      collective capacity, or as an interactive person-environment process. Resilience
      was most often reported as low-moderate, with positive correlations with
      hardiness, self-esteem, life and job satisfaction, and negative correlations with
      depression and burnout. A resilience programme improved mental health nurses'
      coping self-efficacy and capacity to regulate thoughts and emotions and developed
      their resilient practice. Use of contemporary resilience definitions will inform
      more consistent investigation and progressively scaffold knowledge of this
      emergent construct in mental health nursing. Future research on the
      implementation of resilience programmes and resilience-building strategies for
      mental health nurses at the individual, work unit, and organizational levels is
      needed.

PMID- 30294938
TI  - A systematic review and meta-analysis of nutrition interventions for chronic
      noncancer pain.
AB  - BACKGROUND: This systematic review aimed to evaluate the impact of nutrition
      interventions on participant reported pain severity and intensity in populations
      with chronic pain. METHODS: Eight databases were systematically searched for
      studies that included adult populations with a chronic pain condition, a
      nutrition intervention and a measure of pain. Where possible, data were pooled
      using meta-analysis. Seventy-one studies were included, with 23 being eligible
      for meta-analysis. RESULTS: Studies were categorised into four groups: (i)
      altered overall diet with 12 of 16 studies finding a significant reduction in
      participant reported pain; (ii) altered specific nutrients with two of five
      studies reporting a significant reduction in participant reported pain; (iii)
      supplement-based interventions with 11 of 46 studies showing a significant
      reduction in pain; and (iv) fasting therapy with one of four studies reporting a
      significant reduction in pain. The meta-analysis found that, overall, nutrition
      interventions had a significant effect on pain reduction with studies testing an
      altered overall diet or just one nutrient having the greatest effect.
      CONCLUSIONS: This review highlights the importance and effectiveness of nutrition
      interventions for people who experience chronic pain.

PMID- 30294939
TI  - Obesity and loneliness. Findings from a longitudinal population-based study in
      the second half of life in Germany.
AB  - AIM: Little is known about whether changes to obesity are associated with changes
      in loneliness scores. Therefore, using a longitudinal approach, we aimed to
      determine whether the onset of obesity (explanatory variable) is associated with
      changes in loneliness (outcome measure) among older adults. METHODS: For the
      present study, data from wave 2 (2002) to wave 5 (2014) of the German Ageing
      Survey were analyzed. This is a representative sample of community-dwelling
      individuals in Germany (>=40 years). A validated six-item scale by Gierveld and
      van Tilburg was used to quantify loneliness. Obesity was defined as body mass
      index >=30 kg/m2 . Fixed effects regressions were used. RESULTS: Fixed effects
      regressions showed that loneliness increased with the onset of obesity among men
      but not among women. The sex * obesity interaction term was significant (P =
      0.02). CONCLUSIONS: Findings stress the importance of the onset of obesity for
      loneliness among older men. Weight management strategies might also be a
      promising strategy to reduce loneliness scores.

PMID- 30294941
TI  - How we approach: Severe congenital neutropenia and myelofibrosis due to mutations
      in VPS45.
AB  - Mutations in the VPS45 gene lead to a severe primary immune deficiency
      characterized by severe congenital neutropenia and primary myelofibrosis, leading
      to overwhelming infection and early death. This condition is exceedingly rare
      with only 16 patients previously reported, including four with successful
      hematopoietic stem cell transplantation. We review the pathophysiology underlying
      this condition and detail our approach to treatment, particularly vis-a-vis bone
      marrow transplantation and the challenges of transplanting into a diseased bone
      marrow niche. We provide an update on the progress of our three previously
      reported patients, and two additional patients transplanted at our center.

PMID- 30294940
TI  - Spontaneous primary hypothyroidism in 7 adult cats.
AB  - BACKGROUND: Naturally occurring hypothyroidism in adult cats is rare, with only 4
      cases reported. OBJECTIVES: To describe the historical, clinical, laboratory, and
      scintigraphic features of adult cats with spontaneous hypothyroidism. ANIMALS:
      Seven adult cats referred for suspected hypothyroidism. METHODS: Prospective case
      series. We collected data on cats' signalment, clinical signs, results of
      physical examination, routine laboratory and thyroid hormone testing, and thyroid
      imaging (thyroid scintigraphy or ultrasound). We subsequently treated cats with
      levothyroxine and evaluated their response to treatment. RESULTS: Cats ranged
      from 3.5 to 11 years, with no apparent breed predilection; 6/7 cats were male.
      Only 2/7 cats were initially tested because of signs of hypothyroidism (hair-coat
      changes, lethargy, obesity); others were tested for routine thyroid monitoring or
      palpable thyroid nodules. Four were azotemic (serum creatinine, 2.2-3.4 mg/dL).
      Six of the cats had low serum thyroxine (T4 ) and free T4 (fT4 ) concentrations,
      whereas all 7 cats had high thyroid-stimulating hormone (TSH) concentrations. In
      6/7 cats, thyroid scintigraphy revealed bilateral goiter with intense
      radionuclide uptake; imaging showed no visible thyroid tissue in the other. After
      levothyroxine treatment, serum concentrations of T4 and fT4 increased and TSH
      fell; high serum creatinine normalized in azotemic cats; and repeat imaging
      showed reduction in goiter size. CONCLUSIONS AND CLINICAL IMPORTANCE: Primary
      hypothyroidism develops in adult cats, with a higher prevalence than previously
      thought. Most cats appear to develop a goitrous form of hypothyroidism associated
      with thyroid hyperplasia, whereas thyroid atrophy appears to be less common. With
      levothyroxine replacement, clinical and laboratory abnormalities improve or
      resolve.

PMID- 30294942
TI  - Comprehensive analysis of aberrantly expressed profiles of messenger RNA in
      alcoholic liver disease.
AB  - BACKGROUND: Alcoholic liver disease (ALD) is one of the major cause of morbidity
      and mortality of clinical liver disease worldwide. Until today, although many
      general therapies are carried out and several molecular targets have been
      proposed to act as the potential therapeutic targets, more accurate molecular
      targets and more effective therapeutic methods remain needed. MATERIAL AND
      METHODS: In the study, we analyze the differential expression genes (DEGs)
      between the patients with ALD and healthy controls. Gene Ontology enrichment and
      KEGG signaling pathway analysis are performed to identify the function of DEGs.
      Some significant molecules are proposed to act as the potential therapeutic
      targets for ALD. RNA data of 15 ALD tissues and 7 normal tissues for RNA
      expression analysis were obtained. DEGs in ALD samples compared with normal
      tissues identified through the limma R package and subjected to network analysis.
      RESULTS: As a result, we obtained a total of 274 DEGs that mainly involved in
      biological processes related to the angiogenesis, stress reaction, synthesis, and
      metabolism of organic acids. Network analysis obtained several genes with high
      network degree and fold change. Some significant molecules are proposed to act as
      the potential therapeutic targets for ALD. CONCLUSIONS: Our research identified
      some new progression-related genes of alcohol liver diseases, which could be
      regarded as the new targets for the early diagnosis and therapeutic management in
      ALD.

PMID- 30294943
TI  - Hepatic copper concentrations in 546 dogs (1982-2015).
AB  - BACKGROUND: Copper associated hepatitis (CAH) has been increasingly recognized in
      dogs, and speculation exists that hereditary defects in copper metabolism have
      been exacerbated by increased environmental copper exposure. However, no broad
      epidemiological investigations have been performed to investigate quantitative
      hepatic copper concentrations ([Cu]H ) over time in both dogs that are
      (predisposed breed [PB]), and are not (non-predisposed breed [NPB]), considered
      at-risk for CAH. OBJECTIVES: To investigate [Cu]H in dogs and explore temporal,
      demographic, and histologic associations spanning 34 years. ANIMALS: 546 archived
      liver specimens. METHODS: Retrospective study. Searches of the Michigan State
      University Veterinary Diagnostic Laboratory database identified dogs that had
      undergone hepatic histopathologic assessment. Cases with archived tissue were
      reviewed and classified by breed, time period, and presence or absence of
      hepatitis. Inductively coupled plasma mass spectrometry was used to determine
      [Cu]H . RESULTS: In time period 2009-2015, median [Cu]H were 101 MUg/g and 313
      MUg/g greater than median [Cu]H in time period 1982-1988 for NPB and PB dogs,
      respectively (P < .001 for both comparisons). The proportion of dogs with [CU]H >
      300 MUg/g increased in NPB (28% to 49%) and PB dogs (48% to 71%) during these
      periods (P = .002 for both comparisons). Median [Cu]H in dogs with hepatitis
      increased 3-fold over time in both NPB (P = .004) and PB populations (P < .001).
      CONCLUSIONS AND CLINICAL IMPORTANCE: The frequent recognition of CAH in recent
      years is likely due to the observed increases in [Cu]H over time. Importantly,
      effects are not limited to PB dogs.

PMID- 30294944
TI  - Identification and frequency of the associated genes with virulence and
      antibiotic resistance of Escherichia coli isolated from cow's milk presenting
      mastitis pathology.
AB  - Antimicrobial resistance, genotype, and virulence gene content of Escherichia
      coli isolated from bovine clinical mastitis in Tehran Province, Iran, were
      studied. Two hundred seven (207) milk samples from individual cows presenting
      mastitis symptoms collected from different dairy farms were used to determine the
      presence of specific genes of E. coli responsible for this pathology. Multiplex
      PCR was used to differentiate E. coli isolates into different phylogenetic
      groups/subgroups and to detect their virulence and involved resistance genes. All
      the isolated strains were tested for the susceptibility to 21 antimicrobial
      agents. The results showed that E. coli was detected in 42 (20.3%) samples and
      69% of them belonged to the phylogenetic groups A and B1. The phylogenetic
      subgroup A1 (31%) and subgroup B1 (28.6%) demonstrated the highest prevalence of
      virulence genes (f17c-A, and eae (n = 6), f17b-A, and f17d-A (n = 5), afaD-8,
      afaE-8, aucD, and bfpA (n = 4), clpG and VT (n = 2), and LT and ST genes (n =
      1)). The highest antimicrobial resistance was observed for tetracycline (45.2%)
      followed by streptomycin (26.2%). The antimicrobial resistance genes tetB (31%),
      tetA (28.6%), and aadA (26.2%) were the most prevalent. Moreover, integron class
      1 and 2 were found in 24 (57.1%) and 8 (19%) of the E. coli isolates.

PMID- 30294945
TI  - PARENTS 2 Study: consensus report for parental engagement in the perinatal
      mortality review process.
AB  - OBJECTIVES: Following a perinatal death, a standardised multidisciplinary review
      should take place. Learning from these deaths and engaging parents in this
      process could help prevent future perinatal deaths in line with United Kingdom
      (UK) national and international targets to reduce the number of such deaths by
      2020. Moreover, it would support parents in understanding events around the death
      of their baby. An earlier study (Parents' Active Role and ENgagement in The
      review of their Stillbirth/perinatal death - PARENTS 1 study) found that parents
      would endorse the opportunity to give feedback into the perinatal mortality
      review process (PNMR). In subsequent focus groups, healthcare professionals were
      positive about parental engagement, although they considered there may be
      significant challenges. The objective of this study was to develop core
      principles and recommendations for parental engagement in PNMR in the UK.
      METHODS: We followed a two-round Delphi technique to reach a consensus on core
      principles; including a national consensus workshop and an online questionnaire.
      The consensus meeting was attended by a national panel of stakeholders (clinical
      and academic experts, parent support groups, managers and commissioners) in
      stillbirth, neonatal and bereavement care (n=22). To develop recommendations for
      parental engagement, participants discussed four key areas including: receiving
      feedback from parents; format of the PNMR meeting; the parental pathway; and
      challenging aspects of engaging with parents in reviews. Content analysis was
      conducted to generate recommendations from the meeting for a subsequent,
      anonymous web-based survey. Attendees of the consensus workshop and members of
      the PARENTS 2 Project Advisory Board were asked to rank recommendations using a 9
      point Likert scale from 1 (not important) to 9 (critical). It had been agreed a
      priori, in compliance with established Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) criteria, that 'Consensus' would be achieved
      if over 70% scored the principle as 'critical' (score 7 to 9) and less than 15%
      scored the principle as 'not important' (score 1 to 3). Principles where
      Consensus was achieved would be included in the core recommendations. RESULTS:
      Twenty-five of the 29 invited stakeholders participated in the consensus meeting
      and the subsequent online questionnaire in June 2017 (86.2% response rate).
      Consensus was agreed on 12 core principles. Ninety-six percent agreed that it was
      of critical importance that there should be a face-to-face explanation of the
      PNMR process; 72% considered parents should be offered the opportunity to
      nominate a suitable advocate; 92% believed responses to parents' comments should
      be formally documented; 96% indicated that it was vital for action plans to be
      translated into lessons learnt and that this process is monitored; and 100% of
      stakeholders voted that a plain English summary should be produced for the
      parents following the meeting. There was good agreement on a further seven
      principles. CONCLUSIONS: Key national stakeholders were unanimously supportive of
      parental engagement and agreed on core principles to make it feasible, meaningful
      and robust process. A six-month pilot of parental engagement in the perinatal
      mortality review process (PARENTS 2 Study) in two UK units took place after the
      consensus on core principles. In collaboration with the National Perinatal
      Epidemiology Unit, findings will inform the national standardised perinatal
      mortality review tool (PMRT). This article is protected by copyright. All rights
      reserved.

PMID- 30294946
TI  - Atypical Hemolytic-Uremic Syndrome: An Update on Pathophysiology, Diagnosis, and
      Treatment.
AB  - Atypical hemolytic uremic syndrome (aHUS), a rare variant of thrombotic
      microangiopathy, is characterized by microangiopathic hemolytic anemia,
      thrombocytopenia, and renal impairment. The condition is associated with poor
      clinical outcomes with high morbidity and mortality. Atypical HUS predominantly
      affects the kidneys but has the potential to cause multi-organ system
      dysfunction. This uncommon disorder is caused by a genetic abnormality in the
      complement alternative pathway resulting in over-activation of the complement
      system and formation of microvascular thrombi. Abnormalities of the complement
      pathway may be in the form of mutations in key complement genes or autoantibodies
      against specific complement factors. We discuss the pathophysiology, clinical
      manifestations, diagnosis, complications, and management of aHUS. We also review
      the efficacy and safety of the novel therapeutic agent, eculizumab, in aHUS,
      pregnancy-associated aHUS, and aHUS in renal transplant patients.

PMID- 30294947
TI  - Piezoelectric Biomaterials for Sensors and Actuators.
AB  - Recent advances in materials, manufacturing, biotechnology, and
      microelectromechanical systems (MEMS) have fostered many exciting biosensors and
      bioactuators that are based on biocompatible piezoelectric materials. These
      biodevices can be safely integrated with biological systems for applications such
      as sensing biological forces, stimulating tissue growth and healing, as well as
      diagnosing medical problems. Herein, the principles, applications, future
      opportunities, and challenges of piezoelectric biomaterials for medical uses are
      reviewed thoroughly. Modern piezoelectric biosensors/bioactuators are developed
      with new materials and advanced methods in microfabrication/encapsulation to
      avoid the toxicity of conventional lead-based piezoelectric materials.
      Intriguingly, some piezoelectric materials are biodegradable in nature, which
      eliminates the need for invasive implant extraction. Together, these advancements
      in the field of piezoelectric materials and microsystems can spark a new age in
      the field of medicine.

PMID- 30294948
TI  - Phosphine-Catalyzed Difunctionalization of beta-Fluoroalkyl alpha,beta-Enones: A
      Direct Approach to beta-Amino alpha-Diazo Carbonyl Compounds.
AB  - An efficient and practical phosphine-catalyzed vicinal difunctionalization of
      beta-fluoroalkyl alpha,beta-enones with TMSN3 has been developed. Using dppb as
      the catalyst, the reaction worked efficiently to yield various beta-amino alpha
      diazocarbonyl compounds in high yields (up to 94 %). This work marks the first
      efficient construction of alpha-diazocarbonyl compounds by phosphine catalysis.
      Meanwhile, the asymmetric variant induced by the nucleophilic bifunctional
      phosphine P4 led to various chiral fluoroalkylated beta-amino alpha-diazocarbonyl
      compounds in high yields and enantioselectivity. NMR and ESI-MS studies support
      the existence of the key reaction intermediates. In contrast, beta-azide carbonyl
      compounds would be furnished in good yields from beta-fluoroalkylated beta,beta
      disubstituted enones.

PMID- 30294949
TI  - Developmental gene expression patterns in the brain and liver of Xenopus
      tropicalis during metamorphosis climax.
AB  - Thyroid hormones (THs) induce metamorphosis in amphibians, causing dynamic
      changes, whereas mammalian newborns undergo environmental transition from
      placenta to open air at birth. The similarity between amphibian metamorphosis and
      the mammalian perinatal periods has been repeatedly discussed. However, a
      corresponding developmental gene expression analysis has not yet been reported.
      In this study, we examined the developmental gene expression profiles in the
      brain and liver of Xenopus tropicalis during metamorphosis climax and compared
      them to the respective gene expression profiles of newborn rodents. Many
      upregulated genes identified in the tadpole brain during metamorphosis are also
      upregulated in the rodent brain during the first three postnatal weeks when the
      TH surge occurs. The upregulation of some genes in the brain was inhibited in
      thyroid hormone receptor alpha (TRalpha) knockout tadpoles but not in TRbeta
      knockout tadpoles, implying that brain metamorphosis is mainly mediated by
      TRalpha. The expression of some genes was also increased in the liver during
      metamorphosis climax. Our data suggest that the rodent brain undergoes TH
      dependent remodeling during the first three postnatal weeks as observed in X.
      tropicalis during the larva-to-adult metamorphosis.

PMID- 30294950
TI  - Blood Concentrations of Complement Split Product iC3b and Serum C3 Associate with
      SLE Disease Activity.
AB  - OBJECTIVE: To examine correlations between blood levels of complement split
      product iC3b and serum component C3 with clinically meaningful changes in disease
      activity in patients with systemic lupus erythematosus (SLE). METHODS: 159
      consecutive subjects with American College of Rheumatology or Systemic Lupus
      International Collaborating Clinics classified SLE were enrolled into CASTLE
      (Complement Activation Signatures in Systemic Lupus Erythematosus), a prospective
      observational study. Patients with 1-7 study visits were included in this
      longitudinal analysis. 48 healthy volunteers were enrolled to establish the
      normal reference iC3b/C3 ratio. Serum C3 and C4 were measured by nephelometry and
      blood iC3b levels by a lateral flow assay. SLE disease activity was monitored
      utilizing the Systemic Lupus Erythematosus Disease Activity Index 2K Responder
      Index-50 instrument. RESULTS: iC3b/C3 ratio, double-stranded (ds)DNA antibodies
      (Abs), and supraphysiologic prednisone dose (>7.5 mg/day) each independently
      correlated with SLE disease activity, employing multilevel multiple logistic
      regression analysis. Only the iC3b/C3 ratio was significantly associated with
      clinically meaningful improvements in disease activity among subjects receiving
      supraphysiologic doses of prednisone. iC3b/C3 outperformed C3 and C4 levels
      discriminating both active versus inactive SLE disease and major flares versus no
      disease activity. iC3/C3, dsDNA Abs, ESR, and supraphysiologic prednisone dose
      were independently associated with lupus nephritis, while none were associated
      with SLE rash. The association of iC3b/C3 with nephritis was independent of other
      observed clinical manifestations. CONCLUSION: Blood iC3b/C3 correlates with SLE
      disease activity and clinically meaningful changes. Furthermore, it discriminates
      between active versus inactive SLE, and major flares compared to those patients
      without active disease. This article is protected by copyright. All rights
      reserved.

PMID- 30294951
TI  - Socially isolated older people with mental illness in Tokyo homeless shelters.

PMID- 30294952
TI  - Treating diabetic complications; from large randomized clinical trials to
      precision medicine.
AB  - In the last decades, many large randomized controlled trials have been conducted
      to assess the efficacy and safety of new interventions for the treatment of
      diabetic kidney disease (DKD). Unfortunately, these trials failed to demonstrate
      additional kidney or cardiovascular protection. One of the explanations for the
      failure of these trials appears to be the large variation in drug response
      between individual patients. All trials to date tested a drug which was targeted
      to a large heterogeneous population assuming that every individual will show a
      similar beneficial respond to the drug. Post hoc analyses from the past clinical
      trials, however, suggest that individual patients show a marked variation in drug
      response. This highlights the need to personalize treatment taking proper account
      of the characteristics and preferences of individual patients. Transitioning to a
      personalized therapy approach will have implications for clinical trial designs,
      drug registration and its use in clinical practice. Successful implementation of
      personalized medicine thus requires engagement of multiple stakeholders including
      academic community, pharmaceutical industry, regulatory agencies, health policy
      makers, physicians and patients. This supplement of Diabetes Obesity and
      Metabolism provides a summary on the state-of-the-art of personalized medicine in
      diabetic kidney disease from the views of various stakeholders.

PMID- 30294953
TI  - Precision medicine in diabetes and diabetic kidney disease: Regulatory
      considerations.
AB  - Over the past 15 years, three new classes of drugs, glucagon-like peptide-1 (GLP
      1) receptor agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium
      glucose cotransporter-2 (SGLT-2) inhibitors have been approved to treat type 2
      diabetes based on effects on glycemic control. Although large randomized
      controlled trials have played an important role in characterizing the efficacy
      and safety of these agents on a population level, questions remain about how best
      to individualize therapy and target the "right" medicine to the "right" patient.
      In contrast, few medicines have been approved to treat diabetic kidney disease
      and initiatives have been launched on both sides of the Atlantic to facilitate
      the development of effective personalized medicines for the treatment of diabetic
      kidney disease. Increasingly, "omics," imaging and other biomarkers will be used
      to match patients with therapies to which they are likely to respond best. This
      review addresses regulatory considerations related to precision medicine, draws
      lessons learned from other therapeutic areas and discusses efforts undertaken by
      the European (EMA) and United States (FDA) to facilitate the development of such
      therapies. Moving forward, an integrated approach that makes use of predictive
      preclinical models, innovative trial designs, observational "real-world" data and
      novel statistical methodologies will likely be needed to complement inherently
      smaller RCTs conducted in more selected populations. Patient involvement will
      also be critical. Regulatory agencies are ready to engage in such approaches.

PMID- 30294954
TI  - New clinical trial designs for establishing drug efficacy and safety in a
      precision medicine era.
AB  - Despite advances in pharmacotherapy, diabetic kidney disease (DKD) remains
      associated with a high burden of micro- and macrovascular complications often
      leading to premature mortality. New therapies are highly desirable to mitigate
      the burden of this disease. However, there are a number of barriers that hamper
      drug development in DKD. These include, amongst others, the lengthy and complex
      clinical trials required to prove drug efficacy and safety, inefficiencies in
      clinical trial conduct, and the high costs associated with these development
      programs. In this review a number of aspects are discussed, aiming to identify
      opportunities to transform and innovate drug development for DKD. Many clinical
      trials in DKD, as well as in other areas, face difficulties in timely and
      efficient enrolment of participants. To address this issue a network of sites
      should be created that are continuously recruiting individuals with DKD and
      collecting crucial information that can be used to understand prognosis and
      prognostic factors, and more importantly to serve as a pool of participants for
      recruitment to randomized trials. Second, the current clinical endpoints are late
      events in the progression of DKD. Endpoints based on lesser declines in estimated
      glomerular filtration rate (eGFR) or changes in albuminuria can shorten follow-up
      and/or lead to smaller and cheaper trials. Enrichment by enrolling clinical trial
      populations based on biomarker profiles is another approach that may facilitate
      clinical trial efficiency and conduct. Biomarkers can be used to individualize
      treatment by targeting populations more likely to respond leading to smaller and
      more efficient trials. Finally, using new trial design such as basket, umbrella
      or more broadly platform trials to assess a number of therapies simultaneously
      offers the potential to transform the drug development process in DKD. There are
      a number of opportunities to transform development approaches for new therapies
      for DKD. Platform trials along with appropriate biomarker-based enrichment
      strategies offer the possibility to foster drug development in a precision
      medicine era.

PMID- 30294955
TI  - Implementing personalized medicine in diabetic kidney disease: Stakeholders'
      perspectives.
AB  - The promise of personalized medicine to deliver "the right treatments at the
      right time to the right person" is the next frontier in healthcare. However, to
      implement personalized medicine in chronic diseases such as diabetes mellitus and
      diabetic kidney disease (DKD), a number of different aspects need to be taken
      into account. Better risk stratification and more precise options for treatment
      need to be developed and included in clinical practice guidelines. A patient's
      unique psychological, social and environmental situation also drive disease
      progression and outcomes. Appraising the cost effectiveness of precision
      medicines is necessary, not just as the cost of new therapies, but also the cost
      of diagnosis with novel methodologies and averted complications. As the
      prevalence of DKD grows worldwide to epidemic proportions, challenges such as
      global disparities in resources, access to healthcare and prevalence need to be
      addressed. This review considers these issues to achieve the short and longer
      term goals of implementing personalized medicine in clinical practice.

PMID- 30294956
TI  - An integrative systems biology approach for precision medicine in diabetic kidney
      disease.
AB  - Current therapeutic approaches are ineffective in many patients with established
      diabetic kidney disease (DKD), an epidemic affecting one in three patients with
      diabetes. Early identification of patients at high risk for progression and
      individualizing therapies have the potential to mitigate kidney complications due
      to diabetes. To achieve this, a better understanding of the complex
      pathophysiology of DKD is needed. A system biology approach integrating large
      scale omic data is well suited to unravel the molecular mechanisms driving DKD
      and may offer new perspectives how to personalize therapy. Recent studies indeed
      show that integrating genome scale data sets generated from prospectively
      designed clinical cohort studies with model systems using innovative
      bioinformatics analysis revealed critical molecular pathways in DKD and led to
      the development of candidate prognostic molecular biomarkers. This review seeks
      to provide an overview of the recent progress in the application of the
      integrative systems biology approaches specifically in the field of molecular
      biomarkers for DKD. We will mainly focus the discussion on how to use integrative
      system biology approach to first identify patients at high risk of progression,
      and second to identify patients who may or may not respond to treatment.
      Challenges and opportunities in applying precision medicine in DKD will also be
      discussed.

PMID- 30294957
TI  - Enhancement of transgene expression by nuclear transcription factor Y and CCCTC
      binding factor.
AB  - If a transgene is effectively delivered to a cell, its expression may still be
      limited by epigenetic mechanisms that silence the transgene. Indeed, once the
      transgene reaches the nucleus, it may be bound by histone proteins and condensed
      into heterochromatin or associated with repressor proteins that block
      transcription. In this study, we sought to enhance transgene expression by adding
      binding motifs for several different epigenetic enzymes either upstream or
      downstream of two promoters (CMV and EF1alpha). Screening these plasmids revealed
      that luciferase expression was enhanced 10-fold (10.4 +/- 5.8) by the addition of
      a CCAAT box just upstream of the EF1alpha promoter to recruit nuclear
      transcription factor Y (NF-Y), while inserting a CCCTC-binding factor (CTCF)
      motif downstream of the EF1alpha promoter enhanced expression at least 14-fold
      (14.03 +/- 6.54). ChIP assays confirmed that NF-Y and CTCF bound to the motifs
      that were added to each plasmid, but the presence of NF-Y and CTCF did not
      significantly affect the levels of histone acetylation (H3K9ac) or methylation
      (H3K9me3). Overall, these results show that transgene expression from the
      EF1alpha promoter can be significantly increased with motifs that recruit NF-Y or
      CTCF. (c) 2018 American Institute of Chemical Engineers Biotechnol. Prog., 1-8,
      2018.

PMID- 30294958
TI  - Physical health status of older adults with severe mental illness: The PHiSMI-E
      cohort study.
AB  - The objective was to use various somatic parameters as basis for investigating
      the physical health of older adults with severe mental illnesses (SMI). A cross
      sectional study design is performed by using baseline data from the Physical
      Health in SMI-elderly (PHiSMI-E) study. Data were collected using the Nursing
      Monitoring of Somatic Status and Lifestyle - Mental Health instrument in adults
      aged over 60 with SMI in a large Dutch mental health institute. Ninety-nine
      elderly SMI patients were included. Somatic comorbidity (84.8%), use of somatic
      medication (77.7%) and polypharmacy (67.7%) were prevalent. Extrapyramidal
      symptoms were experienced by 51% of patients, mainly in the subgroup with
      psychotic disorders (75.6%). Unhealthy diet was reported in 16.2%, obesity in
      27.3%, and physical inactivity in 57.6%. Fatigue (67.7%) and dry mouth (66.6%)
      were the commonest reported physical symptoms. Mean VAS score (scale 0-10)
      indicating participants' self-perceived physical health was 6.7 (SD +/- 1.6).
      After division of the total patient group into tertiles based on the VAS scores,
      the lowest tertile was characterized by less physical activity, unhealthier diet,
      more use of medication, more fatigue, somnolence, and inner agitation. In
      conclusion, impaired physical health status was common in these older patients
      with SMI. Although they had more psychiatric and somatic comorbidity than adult
      SMI patients described in the literature, they had a healthier lifestyle. To
      reduce morbidity and premature mortality in these frail patients, it is essential
      that healthcare providers are aware of the high prevalence of somatic comorbidity
      and symptoms, and of their interactions with the psychiatric disorders. This
      study improves our understanding of differences in vulnerability factors of older
      patients with SMI. The (early) detection of somatic comorbidities may improve
      long-term health outcomes of these patients.

PMID- 30294959
TI  - Arterial damage and cognitive impairment in patients with chronic kidney disease.

PMID- 30294961
TI  - Innate lymphoid cells, mediators of tissue homeostasis, adaptation and disease
      tolerance.
AB  - Innate lymphoid cells (ILC) are a recently identified group of tissue-resident
      innate lymphocytes. Available data support the view that ILC or their progenitors
      are deposited and retained in tissues early during ontogeny. Thereby, ILC become
      an integral cellular component of tissues and organs. Here, we will review the
      intriguing relationships between ILC and basic developmental and homeostatic
      processes within tissues. Studying ILC has already led to the appreciation of the
      integral roles of immune cells in tissue homeostasis, morphogenesis, metabolism,
      regeneration, and growth. This area of immunology has not yet been studied in
      depth but is likely to reveal important networks contributing to disease
      tolerance and may be harnessed for future therapeutic approaches.

PMID- 30294962
TI  - Type 2 innate lymphoid cells in the induction and resolution of tissue
      inflammation.
AB  - Type 2 immunity against pathogens is tightly regulated to ensure appropriate
      inflammatory responses that clear infection and prevent excessive tissue damage.
      Recent research has shown that type 2 innate lymphoid cells (ILC2s) contribute to
      steady-state tissue integrity and exert tissue-specific functions. However, upon
      exposure to inflammatory stimuli, they also initiate and amplify type 2
      inflammation by inducing mucus production, eosinophilia, and Th2 differentiation.
      In this review, we discuss the regulation of ILC2 activation by transcription
      factors and metabolic pathways, as well as by extrinsic signals such as
      cytokines, lipid mediators, hormones, and neuropeptides. We also review recent
      discoveries about ILC2 plasticity and heterogeneity in different tissues, as
      revealed partly through single-cell RNA sequencing of transcriptional responses
      to various stimuli. Understanding the tissue-specific pathways that regulate ILC2
      diversity and function is a critical step in the development of potential
      therapies for allergic diseases.

PMID- 30294963
TI  - The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying
      mechanisms.
AB  - Group 2 innate lymphoid cells (ILC2s) play critical roles in the induction of
      type 2 inflammation, response to parasite infection, metabolic homeostasis, and
      tissue repair. These multifunctional roles of ILC2s are tightly controlled by
      complex regulatory systems in the local microenvironment, the disruption of which
      may cause various health problems. This review summarizes up-to-date knowledge
      regarding positive and negative regulators for ILC2s based on their function and
      signaling pathways, including activating cytokines (IL-33, IL-25; MAPK, NF-kappaB
      pathways), co-stimulatory cytokines (IL-2, IL-7, IL-9, TSLP; STAT5, IL-4; STAT6,
      TNF superfamily; MAPK, NF-kappaB pathways), suppressive cytokines (type1 IFNs,
      IFN-gamma, IL-27; STAT1, IL-10, TGF-beta), transdifferentiation cytokines (IL-12;
      STAT4, IL-1beta, IL-18), lipid mediators (LTC4, LTD4, LTE4, PGD2; Ca2+ -NFAT
      pathways, PGE2, PGI2; AC/cAMP/PKA pathways, LXA4, LTB4), neuropeptides (NMU; Ca2+
      -NFAT, MAPK pathways, VIP, CGRP, catecholamine, acetylcholine), sex hormones
      (androgen, estrogen), nutrients (butyrate; HDAC inhibitors, vitamins), and cell
      to-cell interactions (ICOSL-ICOS; STAT5, B7-H6-NKp30, E-cadherin-KLRG1). This
      comprehensive review affords a better understanding of the regulatory network
      system for ILC2s, providing impetus to develop new treatment strategies for ILC2
      related health problems.

PMID- 30294960
TI  - Neuroendocrine regulation of innate lymphoid cells.
AB  - The activities of the immune system in repairing tissue injury and combating
      pathogens were long thought to be independent of the nervous system. However, a
      major regulatory role of immunomodulatory molecules released locally or
      systemically by the neuroendocrine system has recently emerged. A number of
      observations and discoveries support indeed the notion of the nervous system as
      an immunoregulatory system involved in immune responses. Innate lymphoid cells
      (ILCs), including natural killer (NK) cells and tissue-resident ILCs, form a
      family of effector cells present in organs and mucosal barriers. ILCs are
      involved in the maintenance of tissue integrity and homeostasis. They can also
      secrete effector cytokines rapidly, and this ability enables them to play early
      roles in the immune response. ILCs are activated by multiple pathways including
      epithelial and myeloid cell-derived cytokines. Their functions are also regulated
      by mediators produced by the nervous system. In particular, the peripheral
      nervous system, through neurotransmitters and neuropeptides, works in parallel
      with the hypothalamic-pituitary-adrenal and gonadal axis to modulate inflammatory
      events and maintain homeostasis. We summarize here recent findings concerning the
      regulation of ILC activities by neuroendocrine mediators in homeostatic and
      inflammatory conditions.

PMID- 30294964
TI  - Innate lymphoid cells in lung infection and immunity.
AB  - In recent years, innate lymphoid cells (ILCs) have emerged as key mediators of
      protection and repair of mucosal surfaces during infection. The lung, a dynamic
      mucosal tissue that is exposed to a plethora of microbes, is a playground for
      respiratory infection-causing pathogens which are not only a major cause of
      fatalities worldwide, but are also associated with comorbidities and decreased
      quality of life. The lung provides a rich microenvironment to study ILCs in the
      context of innate protection mechanisms within the airways, unraveling their
      distinct functions not only in health but also in disease. In this review, we
      discuss how pulmonary ILCs play a role in protection against viral, parasitic,
      bacterial, and fungal challenge, along with the mechanisms underlying this ILC
      mediated immunity.

PMID- 30294966
TI  - Deconstructing deployment of the innate immune lymphocyte army for barrier
      homeostasis and protection.
AB  - The study of the immune system has shifted from a purely dichotomous separation
      between the innate and adaptive arms to one that is now highly complex and
      reshaping our ideas of how steady-state health is assured. It is now clear that
      immune cells do not neatly fit into these two streams and immune homeostasis
      depends on continual dialogue between multiple lineages of the innate (including
      dendritic cells, innate lymphoid cells, and unconventional lymphocytes) and
      adaptive (T and B lymphocytes) arms together with a finely tuned synergy between
      the host and microbes which is essential to ensure immune homeostasis. Innate
      lymphoid cells are critical players in this new landscape. Here, we discuss
      recent studies that have elucidated in detail the development of ILCs from their
      earliest progenitors and examine factors that influence their identification and
      ability to drive immune homeostasis and long-term immune protection.

PMID- 30294967
TI  - Introduction: Basic and emerging concepts in ILC biology.

PMID- 30294968
TI  - Thinking differently about ILCs-Not just tissue resident and not just the same as
      CD4+ T-cell effectors.
AB  - Innate lymphoid cells (ILCs) resemble adaptive T lymphocytes based on
      transcription factor expression, cytokine production, and their presumptive roles
      in immunity, but are activated for effector function through cytokine signaling
      and not antigen-specific receptors. The prevailing view is that ILCs adapt to
      specific microenvironments during development and operate as tissue-resident
      cells in co-operation with antigen-specific T cells to provide host protection
      and contribute to tissue maintenance. In particular, conventional models equate
      the activity of different ILC subsets with CD4+ effector T-cell types based on
      corresponding transcription factor expression and a potential for comparable
      cytokine production. Based on recent data from our laboratory, we suggest that
      these views on tissue residence and parallel functioning to CD4+ T cells are too
      restrictive. Our findings show that ILC2s can be mobilized from the gut under
      inflammatory conditions and contribute to distal immunity in the lungs during
      infection, whereas gut-resident ILC3s operate in a quite distinct manner from
      Th17 CD4+ effector cells in responding to commensal microbes, with important
      implications for control of metabolic homeostasis. In this review, we discuss the
      recent advances leading to these revised views of ILC inter-organ trafficking and
      the distinct and complementary function of ILCs with respect to adaptive T cells
      in establishing and maintaining a physiologic host environment.

PMID- 30294969
TI  - New insights into the function, development, and plasticity of type 2 innate
      lymphoid cells.
AB  - Group 2 innate lymphoid cells (ILC2s) are the most well defined group of ILCs.
      ILC2 development is controlled by the GATA-3 transcription factor and these cells
      produce archetypal type 2 cytokines, such as IL-5 and IL-13. These cytokines
      mediate parasite expulsion and tissue repair, but also contribute to type 2
      inflammatory diseases, including allergy, asthma and chronic rhinosinusitis with
      nasal polyps. In response to tightly regulated local environmental cues ILCs can
      generate characteristics of other subtypes, a process known as plasticity. Recent
      advances in the ILC2 field has led to the discovery that ILC2s can promptly shift
      to functional IFN-gamma-producing ILC1s or IL-17-producing ILC3s, depending on
      the cytokines and chemokines produced by antigen presenting cells or epithelial
      cells. Due to yet unknown triggers, this complex network of signals may become
      dysregulated. In this review, we will discuss general ILC characteristic, ILC2
      development, plasticity, memory function, and implications in disease.

PMID- 30294965
TI  - JAK/STAT signaling in regulation of innate lymphoid cells: The gods before the
      guardians.
AB  - Immunity to pathogens is ensured through integration of early responses mediated
      by innate cells and late effector functions taking place after terminal
      differentiation of adaptive lymphocytes. In this context, innate lymphoid cells
      (ILCs) and adaptive T cells represent a clear example of how prototypical
      effector functions, including polarized expression of cytokines and/or cytotoxic
      activity, can occur with overlapping modalities but different timing. The ability
      of ILCs to provide early protection relies on their poised epigenetic state,
      which determines their propensity to quickly respond to cytokines and to activate
      specific patterns of signal-dependent transcription factors. Cytokines activating
      the Janus kinases (JAKs) and members of the signal transducer and activator of
      transcription (STAT) pathway are key regulators of lymphoid development and
      sustain the processes underlying T-cell activation and differentiation. The role
      of the JAK/STAT pathway has been recently extended to several aspects of ILC
      biology. Here, we discuss how JAK/STAT signals affect ILC development and
      effector functions in the context of immune responses, highlighting the molecular
      mechanisms involved in regulation of gene expression as well as the potential of
      targeting the JAK/STAT pathway in inflammatory pathologies.

PMID- 30294972
TI  - A 46,XX testicular disorder of sex development caused by a Wilms' tumour Factor-1
      (WT1) pathogenic variant.
AB  - Molecular diagnosis is rarely established in 46,XX testicular (T) disorder of sex
      development (DSD) individuals with atypical genitalia. The Wilms' tumour factor-1
      (WT1) gene is involved in early gonadal development in both sexes. Classically,
      WT1 deleterious variants are associated with 46,XY disorders of sex development
      (DSD) because of gonadal dysgenesis. We report a novel frameshift WT1 variant
      identified in an SRY-negative 46,XX testicular DSD girl born with atypical
      genitalia. Target massively parallel sequencing involving DSD-related genes
      identified a novel heterozygous WT1 c.1453_1456del; p.Arg485Glyfs*14 variant
      located in the fourth zinc finger of the protein which is absent in the
      population databases. Segregation analysis and microsatellite analysis confirmed
      the de novo status of the variant that is predicted to be deleterious by in
      silico tools and to increase WT1 target activation in crystallographic model.
      This novel and predicted activating frameshift WT1 variant leading to the 46,XX
      testicular DSD phenotype includes the fourth zinc-finger DNA-binding domain
      defects in the genetic aetiology of 46,XX DSD.

PMID- 30294973
TI  - A Density Functional Theoretical Study on the Charge-Transfer Enhancement in
      Surface-Enhanced Raman Scattering.
AB  - The chemical enhancement due to ground-state charge transfer (GSCT) and photon
      driven charge transfer (PDCT) in surface-enhanced Raman scattering (SERS) has
      been investigated by density functional theory. Para-substituted thiophenol
      derivatives adsorbed on silver and gold surfaces are selected as model systems to
      evaluate the chemical enhancement factor. By changing the functional groups on
      thiophenol, we are allowed to modulate the chemical interactions between the
      thiophenol and the metal cluster in both ground state and charge transfer excited
      state. Both off-resonance and pre-resonance SERS spectra are simulated to
      calculate the chemical enhancement factors. The GSCT enhancement factor, EFGSCT ,
      shows a roughly linear relationship to (omegaTP /omegaM-TP )4 , where omegaTP
      denotes the HOMO-LUMO gap of free molecule, and omegaM-TP denotes the energy
      difference between the HOMO of the molecule and the LUMO of the metal. The PDCT
      enhancement factor, EFPDCT , is governed by the energy difference between the
      incident light energy and the excitation energy to the CT excited state. EFPDCT
      first increases and then decreases with the increase of incident light energy.

PMID- 30294971
TI  - Metabolic regulation of innate and adaptive lymphocyte effector responses.
AB  - Innate and adaptive lymphocytes employ diverse effector programs that provide
      optimal immunity to pathogens and orchestrate tissue homeostasis, or conversely
      can become dysregulated to drive progression of chronic inflammatory diseases.
      Emerging evidence suggests that CD4+ T helper cell subsets and their innate
      counterparts, the innate lymphoid cell family, accomplish these complex
      biological roles by selectively programming their cellular metabolism in order to
      instruct distinct modules of lymphocyte differentiation, proliferation, and
      cytokine production. Further, these metabolic pathways are significantly
      influenced by tissue microenvironments and disease states. Here, we summarize our
      current knowledge on how cell-intrinsic metabolic factors modulate the context
      dependent bioenergetic pathways that govern innate and adaptive lymphocytes.
      Further, we propose that a greater understanding of these pathways may lead to
      the identification of unique features in each population and provoke the
      development of novel therapeutic strategies to modulate lymphocytes in health and
      disease.

PMID- 30294970
TI  - Spatial and temporal coordination of antiviral responses by group 1 ILCs.
AB  - Group 1 innate lymphocytes consist of a phenotypically, spatially, and
      functionally heterogeneous population of NK cells and ILC1s that are engaged
      during pathogen invasion. We are only beginning to understand the context
      dependent roles that different subsets of group 1 innate lymphocytes play during
      homeostatic perturbations. With a focus on viral infection, this review
      highlights the organization and regulation of spatially and temporally distinct
      waves of NK cell and ILC1 responses that collectively serve to achieve optimal
      viral control.

PMID- 30294975
TI  - Polyketide and Prenylxanthone Derivatives from the Endophytic Fungus Aspergillus
      sp. TJ23.
AB  - Eight secondary metabolites, including a new polyketide, named asperetide (1) and
      a new prenylxanthone derivative, called asperanthone (4), and six known
      compounds, (S)-3-butyl-7-methoxyphthalide (2), ruguloxanthone C (3), tajixanthone
      hydrate (5), tajixanthone methanoate (6), salimyxin B (7), and ergosterol (8),
      were isolated and identified from the medicinal plant-derived fungus, Aspergillus
      sp. TJ23. The new structures and their absolute configurations were elucidated
      via multiple methods, including 1D- and 2D-NMR, HR-ESI-MS, UV, IR, and the
      electronic circular dichroism (ECD) calculations. All of the isolates were
      characterized from the strain for the first time. The in vitro bioassay showed
      that compounds 3-5 and 8 exerted inhibitory activities against five cancer cell
      lines (B16, MDA-MB-231, 4T1, HepG2, and LLC) with IC50 values ranging from 5.13
      to 36.8 MUm.

PMID- 30294974
TI  - Exercise during hemodialysis does not affect the phenotype or prothrombotic
      nature of microparticles but alters their proinflammatory function.
AB  - Hemodialysis patients have dysfunctional immune systems, chronic inflammation and
      comorbidity-associated risks of cardiovascular disease (CVD) and infection.
      Microparticles are biologically active nanovesicles shed from activated
      endothelial cells, immune cells, and platelets; they are elevated in hemodialysis
      patients and are associated with chronic inflammation and predictive of CVD
      mortality in this group. Exercise is advocated in hemodialysis to improve
      cardiovascular health yet acute exercise induces an increase in circulating
      microparticles in healthy populations. Therefore, this study aimed to assess
      acute effect of intradialytic exercise (IDE) on microparticle number and
      phenotype, and their ability to induce endothelial cell reactive oxygen species
      (ROS) in vitro. Eleven patients were studied during a routine hemodialysis
      session and one where they exercised in a randomized cross-over design.
      Microparticle number increased during hemodialysis (2064-7071 microparticles/MUL,
      P < 0.001) as did phosphatidylserine+ (P < 0.05), platelet-derived (P < 0.01) and
      percentage procoagulant neutrophil-derived microparticles (P < 0.05), but this
      was not affected by IDE. However, microparticles collected immediately and 60 min
      after IDE (but not later) induced greater ROS generation from cultured
      endothelial cells (P < 0.05), suggesting a transient proinflammatory event. In
      summary IDE does not further increase prothrombotic microparticle numbers that
      occurs during hemodialysis. However, given acute proinflammatory responses to
      exercise stimulate an adaptation toward a circulating anti-inflammatory
      environment, microparticle-induced transient increases of endothelial cell ROS in
      vitro with IDE may indicate the potential for a longer-term anti-inflammatory
      adaptive effect. These findings provide a crucial evidence base for future
      studies of microparticles responses to IDE in view of the exceptionally high risk
      of CVD in these patients.

PMID- 30294976
TI  - Available and future treatments for atypical parkinsonism. A systematic review.
AB  - AIMS: Success in treating patients with atypical parkinsonian syndromes, namely
      progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), multiple
      system atrophy (MSA), Parkinson's disease with dementia (PDD), and Lewy body
      dementia with (LBD), remains exceedingly low. The present work overviews the most
      influential research literature collected on MEDLINE, ISI Web of Science,
      Cochrane Library, and Scopus for available treatment in atypical parkinsonisms
      without time restriction. DISCUSSION: Transdermal rotigotine, autologous
      mesenchymal stem cells, tideglusib, and coenzyme Q10 along with donepezil,
      rivastigmine, memantine, and the deep brain stimulation have shown some benefits
      in alleviating symptoms in APS. Moreover, many new clinical trials are ongoing
      testing microtubule stabilizer, antitau monoclonal antibody, tau acetylation
      inhibition, cell replacement, selective serotonin reuptake inhibitor, active
      immunization, inhibition of toxic alpha-synuclein oligomers formation, and
      inhibition of microglia. CONCLUSION: A detailed knowledge of the pathological
      mechanism underlying the disorders is needed, and disease-modifying therapies are
      required to offer better therapeutic options to physician and caregivers of APS
      patients.

PMID- 30294977
TI  - Towards take-all control: a C-21beta oxidase required for acylation of triterpene
      defence compounds in oat.
AB  - Oats produce avenacins, antifungal triterpenes that are synthesized in the roots
      and provide protection against take-all and other soilborne diseases. Avenacins
      are acylated at the carbon-21 position of the triterpene scaffold, a modification
      critical for antifungal activity. We have previously characterized several steps
      in the avenacin pathway, including those required for acylation. However,
      transfer of the acyl group to the scaffold requires the C-21beta position to be
      oxidized first, by an as yet uncharacterized enzyme. We mined oat transcriptome
      data to identify candidate cytochrome P450 enzymes that may catalyse C-21beta
      oxidation. Candidates were screened for activity by transient expression in
      Nicotiana benthamiana. We identified a cytochrome P450 enzyme AsCYP72A475 as a
      triterpene C-21beta hydroxylase, and showed that expression of this enzyme
      together with early pathway steps yields C-21beta oxidized avenacin
      intermediates. We further demonstrate that AsCYP72A475 is synonymous with Sad6, a
      previously uncharacterized locus required for avenacin biosynthesis. sad6 mutants
      are compromised in avenacin acylation and have enhanced disease susceptibility.
      The discovery of AsCYP72A475 represents an important advance in the understanding
      of triterpene biosynthesis and paves the way for engineering the avenacin pathway
      into wheat and other cereals for control of take-all and other diseases.

PMID- 30294979
TI  - The aggressive child.
AB  - Aggression in children is a common transdiagnostic symptom associated with a wide
      range of developmental and mental health problems. It emerges early and without
      intervention, may increase in severity as the child grows stronger. Aggressive
      children are more likely to experience physical and mental illness, unemployment,
      poverty and forensic problems as adults. Strategies to prevent aggression must
      address risk factors: low maternal education, adolescent pregnancy, in utero
      exposure to tobacco and alcohol, poverty, coercive parenting, childhood
      maltreatment and bullying victimisation. The aggressive child requires a
      comprehensive assessment to identify and manage underlying or comorbid problems,
      to understand the reasons for the aggressive behaviour and to detect modifiable
      factors that exacerbate or perpetuate the aggression. Psychosocial interventions
      include parenting skills training and child-directed cognitive behavioural
      therapy, whereas pharmacotherapy may be used to treat underlying developmental or
      mental health problems or to manage the aggression.

PMID- 30294978
TI  - Occupational radiation exposure to nursing staff during cardiovascular
      fluoroscopic procedures: A review of the literature.
AB  - Fluoroscopy is a method used to provide real time x-ray imaging of the body
      during medical procedures to assist with medical diagnosis and treatment. Recent
      technological advances have seen an increase in the number of fluoroscopic
      examinations being performed. Nurses are an integral part of the team conducting
      fluoroscopic investigations and are often located close to the patient resulting
      in an occupational exposure to radiation. The purpose of this review was to
      examine recent literature which investigates occupational exposure received by
      nursing staff during cardiovascular fluoroscopic procedures. Articles published
      between 2011 and 2017 have been searched and comprehensively reviewed on the
      referenced medical search engines. Twenty-four relevant studies were identified
      among which seventeen investigated nursing dose comparative to operator dose.
      Seven researched the effectiveness of interventions in reducing occupational
      exposure to nursing staff. While doctors remain at the highest risk of exposure
      during procedures, evidence suggests that nursing staff may be at risk of
      exceeding recommended dose limits in some circumstances. There is also evidence
      of inconsistent use of personal protection such as lead glasses and skull caps by
      nursing staff to minimize radiation exposure. Conclusions: The review has
      highlighted a lack of published literature focussing on dose to nurses. There is
      a need for future research in this area to inform nursing staff of factors which
      may contribute to high occupational doses and of methods for minimizing the risk
      of exposure, particularly regarding the importance of utilizing radiation
      protective equipment.

PMID- 30294980
TI  - Transgender adolescents and legal reform: How improved access to healthcare was
      achieved through medical, legal and community collaboration.
AB  - Transgender children and adolescents face hardships in all domains of their
      lives, with many experiencing family rejection, social exclusion, discrimination,
      bullying and assaults. The mental health implications of these experiences
      include high rates of depression, anxiety, self-harm and attempted suicide.
      Gender-affirming social support and medical treatment has been shown to
      ameliorate the poor mental health outcomes of transgender youth, with those who
      are supported in their social and medical transition reporting rates of
      depression and self-worth equivalent to general population levels. Advocacy
      efforts that improve access to support and medical treatment are therefore likely
      to produce significant positive health and well-being outcomes for this
      vulnerable population. The transgender community in Australia identified the
      legal restrictions placed on children and adolescents accessing medical treatment
      as a significant barrier to positive psychological well-being. Australian law,
      unique internationally, required the parents of transgender adolescents to apply
      for court authorisation prior to the commencement of their child's gender
      affirming medical treatment. Concerned by the harm created by this process, a
      coalition of experts, including transgender children, adolescents and their
      parents, as well as academic and clinical experts in the fields of law and
      medicine, was created to advocate for reform. Over a period of approximately 4
      years, a collaborative process was undertaken, which ultimately led to law reform
      and improved access to medical treatment for the transgender community.

PMID- 30294981
TI  - Sleep in children with neurodevelopmental difficulties.
AB  - Sleep disorders in children with neurodevelopmental disorders are complex and
      reflect underlying genetic/biological and behavioural components. The sleep
      disorders are the same as in the typically developing child, although there may
      be some modifications to the presentation or the frequency depending on the
      phenotype. Consideration of the known phenotypes and environmental issues are
      important in defining management strategies. Despite this complexity, defined
      behavioural strategies with good sleep hygiene can have a significant effect on
      the sleep problem and on parental management of the behaviours.

PMID- 30294982
TI  - Transition to adult mental health services for young people with an intellectual
      disability.
AB  - People with intellectual disabilities (ID) experience high rates of mental health
      problems, particularly during the period of transition to adulthood. It is
      therefore important that the transition from child- to adult-oriented health
      services for people with ID is well managed to ensure appropriate orientation to
      ongoing adult mental health care. The purpose of this paper is to summarise the
      impact and experience of transition to adult mental health care for people with
      ID and those who support them, as well as issues related to current policy and
      practice in this area. Several opportunities for improvement are identified in
      the broad areas of policy, service structure and organisation, research and
      workforce capacity. Enhancements in these areas will lead to improved outcomes
      for young people with ID transitioning from child- to adult-oriented mental
      health care.

PMID- 30294983
TI  - Specific learning disability.
AB  - Specific learning disabilities (SLD) have an impact on discrete areas of academic
      function. They result in a level of difficulty that is unexpected when considered
      in the context of a student's overall intellectual and academic competence. A
      common example is dyslexia, an SLD that affects the acquisition of literacy.
      Medical professionals have an important role to play in the evaluation and
      management of SLD. The medical role is founded on the fact that these conditions
      are biologically based and have the potential to cause significant harm for the
      developing child. Even if details of biological causation are not possible to
      demonstrate for individual children, medical professionals may, nevertheless,
      make an important judgement call regarding the likelihood of aetiology. When
      learning problems are medically based, it is clearly unreasonable to expect
      children to do more than they are able and to learn faster than is reasonable.
      Advocacy around these biological presumptions and their implications is a major
      contribution to the well-being of children who have SLD.

PMID- 30294984
TI  - Responding to fetal alcohol spectrum disorder in Australia.
AB  - Fetal alcohol spectrum disorder (FASD) is a significant public health issue in
      Australia that is poorly diagnosed, chronic and costly. FASD is a diffuse
      acquired brain injury secondary to prenatal alcohol exposure. The prevalence rate
      of FASD among the general population in Australia is currently unknown; however,
      an Australian study in a selected high-risk population reported some of the
      highest rates of FASD in the world. A common misconception among clinicians is
      that a child must have 'the face' of FASD to have the disorder. This is
      incorrect. The three sentinel facial features only occur in the minority of
      individuals with FASD. FASD should be considered as a 'whole body' disorder as
      increased susceptibility to chronic health problems suggests suboptimal in utero
      environments places the individual at risk of later disease. Clinicians are
      reluctant to consider FASD as a possible diagnosis because of the concern of
      inducing stigma; however, this concern is neither supported by the evidence nor
      patient stories. The Australian Guide to the Diagnosis of FASD is now available
      to assist health professionals in providing timely and accurate diagnoses, which
      can lead to improved outcomes via evidence-based intervention and is an important
      first step in future prevention.

PMID- 30294985
TI  - Models of care in neurodevelopmental-behavioural paediatrics.
AB  - In Australia, children with developmental-behavioural presentations experience
      large variations in both access to specialist health care and in the care they
      receive from specialists. A recent survey of members of the Neurodevelopmental
      and Behavioural Paediatric Society of Australasia confirmed that this variation
      persists even among public services provided by paediatric doctors with a special
      interest in this field. In this article, we discuss the challenges of
      establishing a single model of developmental-behavioural paediatric care and set
      out principles of best practice in the field. An essential part of working
      towards excellence in care involves defining our outcomes, utilising standardised
      measures, collecting systematic data, working in partnership with families to
      address their concerns and goals, participating in reflective practice and
      demonstrating a willingness to change current practice based on the results.

PMID- 30294986
TI  - Anxiety-related disorders: An overview.
AB  - Anxiety-related disorders are common in the child and adolescent population. They
      cause significant distress, which can affect social, emotional, family and
      academic functioning. They frequently present in general paediatric and primary
      care settings. Comprehensive assessment should include the child as well as
      parent and family functioning because anxiety-related disorders in other family
      members are common and, if untreated, can affect outcomes for the child. There
      are good evidence-based psychological interventions available, which should be
      the first line of treatment offered; accessing appropriate therapies for an
      adequate duration of treatment can, however, be challenging. Medication,
      particularly selective serotonin reuptake inhibitors, may have a role to play but
      should be used in the context of psychologically based therapies. Prevention of
      anxiety-related disorders in childhood is a major public health issue. Prevention
      programmes are available and should commence in the antenatal period through
      infancy, early childhood and adolescence, promoting positive attachments and
      resilience.

PMID- 30294987
TI  - Motor impairments in children: More than just the clumsy child.
AB  - Developmental co-ordination disorder is a motor skill disorder that affects an
      estimated 5-6% of children but lacks recognition and understanding, leading to
      under-diagnosis. Essential for diagnosis is a marked impairment in motor co
      ordination that significantly impacts daily living, including education. Although
      'clumsiness' is often dismissed, the impact of this disorder is significant and
      extends beyond motor skills into physical and psychological health and
      educational and vocational success. This is discussed here with regard to the
      framework of the International Classification of Functioning, Disability and
      Health. This review also discusses the importance of an accurate, early diagnosis
      and factors that inhibit this; dual diagnosis with comorbid neurodevelopmental
      disorders; the multidisciplinary approach to diagnosis and the role of the
      paediatrician within this; and current evidence regarding the most effective
      interventions.

PMID- 30294988
TI  - Child with multiple problems: Clinical complexity and uncertainty.
AB  - When practising neurodevelopmental-behavioural paediatrics, responsibility rests
      with the individual clinician to interpret research evidence in their daily work.
      This is not necessarily an easy task. Children do not usually present with
      single, easily definable problems. Complexity and uncertainty are present from
      the outset due to heterogeneity inherent in the diagnoses available, patterns of
      comorbid problems and the unique challenges of each child's social context. This
      article examines the resulting clinical challenge and offers potential responses.
      Rather than striving to eliminate uncertainty with strategies such as extensive
      assessment, the goal is to work effectively and efficiently within the limits of
      what can be readily known. Suggested strategies address complexity by considering
      the components of what is going on (biological, developmental, transactional) as
      hypotheses shared within each child's system of care. These hypotheses can then
      be tested and revised systematically as further information arises along the
      journey of treatment and longitudinal care.

PMID- 30294989
TI  - Children who soil: A review of the assessment and management of faecal
      incontinence.
AB  - Soiling is a common and distressing condition affecting children. In the vast
      majority of patients, it is associated with constipation. Most constipation is
      functional and is best thought of as difficulty achieving adequate bowel
      emptying. In a small minority of patients, there is no associated constipation,
      so-called non-retentive faecal incontinence. The aetiology of this latter
      condition in children remains unclear. The mainstay of management in all cases is
      a regular toileting programme, together with laxatives as required. This must be
      individualised considering the diagnosis, the age of the child and the
      psychosocial factors affecting the child and family. The diagnosis is made with a
      thorough history and examination, supplemented in some cases with targeted
      investigations. Engaging the child and family in a long-term treatment programme
      (at least 6 months to 2 years) is essential for treatment success. The following
      clinical practice guideline and algorithm for the assessment and management of
      children who soil represents consensus opinion using available evidence.

PMID- 30294990
TI  - Use of psychotropic medications in general paediatric practice.
AB  - Paediatricians contribute the greatest proportion of prescriptions for
      psychotropic medication to children between the ages of 3 and 14 years in
      Australia. Medications indicated for attention-deficit hyperactivity disorder are
      the most commonly prescribed, followed by antidepressants and antipsychotics.
      Outside treatment for attention-deficit hyperactivity disorder, most prescribing
      is 'off label'. There are few searchable, up-to-date resources to guide
      psychotropic prescribing to children. The skill level required to manage
      pharmacotherapy is determined by the condition and the characteristics of the
      patient. Psychotropic medication should always be considered within the context
      of other interventions and environmental factors that influence emotions,
      cognition and behaviour. Beware the 'medication fallacy' that arises out of a
      misconception that if one medication does not work, there must be another that
      will.

PMID- 30294991
TI  - Diagnosing cerebral palsy in full-term infants.
AB  - More than 50% of infants with cerebral palsy (CP) are born at or near term, with
      the vast majority having pre- or perinatally acquired CP. While some have a
      clinical history predictive of CP, such as neonatal encephalopathy or neonatal
      stroke, others have no readily identifiable risk factors. Paediatricians are
      often required to discriminate generalised motor delay from a variety of other
      diagnoses, including CP. This paper outlines known causal pathways to CP in term
      born infants with a focus on differential diagnosis. Early and accurate diagnosis
      is important as it allows prompt access to early intervention during the critical
      periods of brain development. A combination of clinical history taking, standard
      clinical examination, neuroimaging and genetic testing should be started at the
      time of referral. Attention to the investigation of common comorbidities of CP,
      including feeding and sleep difficulties, and referral to early intervention are
      recommended.

PMID- 30294992
TI  - Attention deficit hyperactivity disorder: Some challenging clinical scenarios.
AB  - Paediatricians generally have good skills in the assessment and management of
      attention deficit hyperactivity disorder. In most cases this is not difficult -
      the paediatrician's role is clear, and evidence-based treatment can be delivered.
      There are however some clinical situations which present diagnostic, ethical
      and/or management dilemmas for paediatricians in relation to possible attention
      deficit hyperactivity disorder. This Viewpoint article addresses some of these
      scenarios.

PMID- 30294993
TI  - Investigating the child with intellectual disability.
AB  - The search for causation is a key component of the assessment of the child with
      intellectual disability. Historically, a specific diagnosis has been achievable
      in only a small minority of these children, but over the last decade, this has
      changed dramatically such that a specific diagnosis is now possible in about half
      of all children with intellectual disability. This improvement has been driven by
      major advances in genetic-testing technologies, the most important of which are
      chromosome microarray and whole exome sequencing. Simultaneously, these
      technological advances have revealed many new genetic syndromes that had
      previously escaped clinical recognition, and demonstrated that the majority of
      severe intellectual disability is caused by pathogenic gene variants that arise
      de novo in the child. Although access to genomic testing is currently limited,
      evidence from health economic studies suggests that this testing is most cost
      effective when performed early in the patient's diagnostic journey.

PMID- 30294994
TI  - Aetiology of childhood apraxia of speech: A clinical practice update for
      paediatricians.
AB  - Childhood apraxia of speech (CAS) is a rare disorder of childhood that can leave
      a watermark of the impacts throughout the lifetime. Since being first described
      in the 1950s, aetiological insights have been limited. At a neurobiological
      level, clinical MRI scans fail to reveal overt neural anomalies in individual
      cases with CAS, although quantitative MRI methods have revealed subtle brain
      anomalies at a group level. Dramatic insights, however, occurred in the past
      decade from the discovery of genetic pathways underlying the phenotype. Several
      single genes and copy number-variant conditions are now associated with CAS
      either in relative isolation, as in the case of FOXP2 variants, or most typically
      in association with other neurodevelopmental conditions, such as epilepsy,
      intellectual disability, motor impairment and autism. CAS requires careful
      differential diagnosis from other childhood speech disorders, but when a severe
      and persistent diagnosis is confirmed, a genetic aetiology should increasingly be
      pursued.

PMID- 30294995
TI  - Recognition of attachment difficulties and developmental trauma is the
      responsibility of all paediatricians.
AB  - This article provides an overview of attachment theory, developmental trauma and
      trauma-informed care for paediatricians. The impact of difficult or impoverished
      parent-child relationships on brain development and long-term health is now well
      known. Recent neuroscience research reveals the adverse neurological impacts of
      developmental trauma and supports the biological basis of attachment theory.
      There is also an increasing body of evidence that childhood adversity is common
      and impacts physical and mental health throughout the life-span. Comprehensive
      paediatric assessment should include an understanding of attachment difficulties
      and developmental trauma. Viewing children and their families through a 'trauma
      informed lens' can provide critical insights into their clinical presentation and
      care needs. All paediatricians should be providing and practicing trauma-informed
      care.

PMID- 30294996
TI  - Tics and Tourette syndrome.
AB  - Tourette syndrome is a heterogeneous disorder. The genetic basis is complex, and
      both in utero and ex utero environmental factors may modify the phenotypic
      expression of the disorder. Inflammation related to aberrations in immune
      activation appears to play a pathogenic role in some cases. Multiple
      neurochemical pathways are involved. Rather than being a pure movement problem,
      tics are now understood to also have a sensory component. This has resulted in
      new psychological therapeutic strategies and other potential treatments.
      Furthermore, comorbidities are common, particularly attention-deficit
      hyperactivity disorder, anxiety and obsessive-compulsive disorder, and often
      cause more difficulties than the tics. The approach to treatment is dependent on
      the degree and types of impairment. For many patients, education, acceptance and
      understanding are all that is needed. In more severe cases, psychological and/or
      pharmacological interventions may be indicated. In this article, the clinical
      features and pathophysiology of Tourette syndrome are reviewed, and a pragmatic
      management approach is discussed.

PMID- 30294997
TI  - Autism: One or many spectrums?
AB  - Our conceptualisation of autism spectrum disorder has changed over time, with
      recent classifications reflecting a heterogeneous clinical presentation now
      regularly encountered in routine general paediatric practice. As the prevalence
      of autism and associated demands for services have increased so has research into
      understanding the cause and trials aimed at providing best care and intervention.
      However, the heterogeneity of autism has meant that no single aetiology can
      account for all differences in presentation, and not all children benefit from
      broad-based interventions. Now is the time to rethink how best to understand
      individual differences in order to focus research efforts and take steps towards
      more sophisticated strategies that go beyond the behaviours we look for when
      making an autism diagnosis. We suggest adopting a dimensional approach to autism
      assessment, with the consideration of eight spectrums of abilities, ways of
      thinking and behaviour. This eight-spectrum approach will assist clinicians to
      consider each individual's strengths and needs and personalise interventions and
      support accordingly. Profiling individual skills across these dimensions may also
      provide researchers with a greater capacity to link causal pathways with specific
      phenotypes, which is needed to develop precision medicine for autism.

PMID- 30294998
TI  - Developmental-behavioural paediatrics in the 21st century.

PMID- 30294999
TI  - Tips for managing treatment-resistant enuresis.
AB  - Enuresis (bedwetting) is common in school-aged children and can impact health,
      psychosocial well-being and quality of life. Although effective treatment is
      available, treatment resistance is encountered in about 50%. This paper discusses
      the management of treatment-resistant enuresis from a multidisciplinary
      perspective. Causes of treatment resistance include lower urinary tract problems,
      constipation, incorrect alarm training techniques, sleep disorders including
      sleep apnoea and psychological comorbidities. Practical suggestions to address
      treatment resistance are offered utilising expertise from clinicians from
      different disciplines.

PMID- 30295000
TI  - To go or not to go: School refusal and its clinical correlates.
AB  - Problematic school refusal that is child motivated is a serious but common
      presentation and a child psychiatric emergency. Mental health professionals,
      paediatricians, educators and parents are often required to work in tandem to
      alleviate concerns due to this. Prolonged absence from school may lead to
      immediate (educational backwardness) and far-reaching effects (psycho-social and
      educational maladjustment). Psychiatric morbidity is high in school-refusing
      children presenting to secondary and tertiary services and is associated with
      temperamental, family and environmental adversities. Outcomes can vary according
      to their age, duration of school refusal and environmental variables.

PMID- 30295001
TI  - Lactic acid production from sugarcane bagasse hydrolysates by Lactobacillus
      pentosus: Integrating xylose and glucose fermentation.
AB  - Lactic acid, traditionally obtained through fermentation process, presents
      numerous applications in different industrial segments, including production of
      biodegradable polylactic acid (PLA). Development of low cost substrate
      fermentations could improve economic viability of lactic acid production, through
      the use of agricultural residues as lignocellulosic biomass. Studies regarding
      the use of sugarcane bagasse hydrolysates for lactic acid production by
      Lactobacillus spp. are reported. First, five strains of Lactobacillus spp. were
      investigated for one that had the ability to consume xylose efficiently.
      Subsequently, biomass fractionation was performed by dilute acid and alkaline
      pretreatments, and the hemicellulose hydrolysate (HH) fermentability by the
      selected strain was carried out in bioreactor. Maximum lactic acid concentration
      and productivity achieved in HH batch were 42.5 g/L and 1.02 g/L h, respectively.
      Hydrolyses of partially delignified cellulignin (PDCL) by two different enzymatic
      cocktails were compared. Finally, fermentation of HH and PDCL hydrolysate
      together was carried out in bioreactor in a hybrid process: saccharification and
      co-fermentation with an initial enzymatic hydrolysis. The high fermentability of
      these process herein developed was demonstrated by the total consumption of
      xylose and glucose by Lactobacillus pentosus, reaching at 65.0 g/L of lactic
      acid, 0.93 g/g of yield, and 1.01 g/L h of productivity. (c) 2018 American
      Institute of Chemical Engineers Biotechnol. Prog., 2018.

PMID- 30295002
TI  - A micro-jet array for economic intensification of gas transfer in bioreactors.
AB  - Bioreactors are of interest for gas-to-liquid conversion of stranded or waste
      industrial gases, such as CO, CH4 , or syngas. Process economics requires
      reduction of bioreactor cost and size while maintaining intense production via
      rapid delivery of gases to the liquid phase (i.e., high kL a). Here, we show a
      novel bioreactor design that outperforms all known technology in terms of gas
      transfer energy efficiency (kL a per power density) while operating at high kL a
      (i.e., near 0.8 s-1 ). The reactor design uses a micro-jet array to break
      feedstock gas into a downward microbubble flow. Hydrodynamic and surfactant
      measurements show the reactor's advanced performance arises from its bubble
      breakage mechanism, which limits fluid shear to a thin plane located at an
      optimal location for bubble breakage. Power dissipation and kL are shown to scale
      with micro-jet diameter rather than reactor diameter, and the micro-jet array
      achieves improved performance compared to classical impinging-jets, ejector, or U
      loop reactors. The hydrodynamic mechanism by which the micro-jets break bubbles
      apart is shown to be shearing the bubbles into filaments then fragmentation by
      surface tension rather than "cutting in half" of bubbles. Guided by these
      hydrodynamic insights, strategies for industrial design are given. (c) 2018
      American Institute of Chemical Engineers Biotechnol. Prog., 2018.

PMID- 30295003
TI  - The "Plan" phase of a Deming cycle: Measurement of quality and outcome of root
      canal treatments in a university hospital.
AB  - INTRODUCTION: In many countries, dental students are taught in private or
      university hospitals where they treat patients under the supervision of teachers.
      Assessing the quality of root canal treatments (RCT) would provide information
      about the quality of care patients receive when treated by students. METHODS:
      This study describes the six-step "Plan" phase of a Plan-Do-Check-Act (PDCA)
      cycle that identifies and analyses clinical practices in endodontics in a
      university dental hospital service. RESULTS: Step 3 reported that the proportion
      of RCTs of adequate quality reached 57.1% and this proportion was significantly
      decreased when specific indicators for treatment difficulties were present. The
      proportion of successful RCTs after 1 year was 65.6%, and its variation was
      influenced by the preoperative periapical status rather than the quality of RCTs.
      The consensual meeting in Step 6 proposed to introduce three new procedures for
      the further Do, Check and Act phases of the PDCA cycle. CONCLUSION: This study
      encourages systematic evaluation of RCTs and provides the first step of the
      methodology that can be reproduced in private and hospital practices where
      students are asked to treat patients.

PMID- 30295005
TI  - Recent Advances in Polyesters for Biomedical Imaging.
AB  - Several synthetic materials exhibiting contrast imaging properties have become
      vital to the field of biomedical imaging. Polymeric biomaterials and metals are
      commonly used imaging agents and can assist in the monitoring of therapy
      response, migration, degradation, changes in morphology, defects, and image
      guided surgery. In comparison to metals, most bio and synthetic polymers lack
      inherent imaging properties. Polymeric biomaterials, specifically polyesters,
      have gained a considerable amount of attention due to their unique properties
      including biocompatibility, biodegradation, facile synthesis, and modification
      capability. Polyester implants and nanomaterials are available on the market or
      are in clinical trials for many applications including: dental implants, cranio
      maxilofacial implants, soft tissue sutures and staples, abdominal wall repair,
      tendon and ligament reconstruction, fracture fixation devices, and coronary drug
      eluting stents. This review aims to provide a summary of the recent developments
      of polyesters with bioimaging contrast properties. The three main approaches to
      prepare bioimaging polyesters (coating, encapsulation, and functionalization) are
      discussed in depth. Furthermore, commonly used imaging modalities including X-ray
      computed tomography, magnetic resonance imaging, ultrasound, fluorescence, and
      radionucleotide polyester contrast agents are highlighted. In each section,
      examples of impactful bioimaging polyesters in the five major imaging modalities
      are evaluated.

PMID- 30295004
TI  - Oxygenation time course and neuromuscular fatigue during repeated cycling sprints
      with bilateral blood flow restriction.
AB  - The aim was to evaluate changes in peripheral and cerebral oxygenation,
      cardiorespiratory, and performance differences, as well as neuromuscular fatigue
      across multiple levels of blood flow restriction (BFR) during a repeated cycling
      sprint test to exhaustion (RST). Participants performed three RST (10-sec maximal
      sprints with 20-sec recovery until exhaustion) with measurements of power output
      and VO2peak as well as oxygenation (near-infrared spectroscopy) of the vastus
      lateralis and prefrontal cortex. Neuromuscular fatigue was assessed by femoral
      nerve stimulation to evoke the vastus lateralis. Tests were conducted with
      proximal lower limb bilateral vascular occlusion at 0%, 45%, and 60% of resting
      pulse elimination pressure. Total work decreased with BFR (52.5 +/- 22.9% at 45%,
      68.6 +/- 32.6% at 60%, P < 0.01 compared with 0%) as VO2peak (12.6 +/- 9.3% at
      45%, 18.2 +/- 7.2% at 60%, compared with 0%, P < 0.01). Decreased changes in
      muscle deoxyhemoglobin (?[HHb]) during sprints were demonstrated at 60% compared
      to 0% (P < 0.001). Changes in total hemoglobin concentrations (?[tHb]) increased
      at both 45% and 60% compared with 0% (P < 0.001). Cerebral ?[tHb] increased
      toward exhaustion (P < 0.05). Maximal voluntary contraction (MVC), voluntary
      activation level (VAL), and root mean square (RMS)/M-wave ratio decreased at 60%
      compared with 0% (P < 0.001, all). MVC and VAL decreased between 45% and 60% (P <
      0.05, both). The application of BFR during RST induced greater changes in tissue
      perfusion (via blood volume, ?[tHb]) suggesting a possible stimulus for vascular
      blood flow regulation. Additionally, high-intensity sprint exercise with partial
      ischemia may challenge cerebral blood flow regulation and influence local fatigue
      development due to protection of cerebral function.

PMID- 30295006
TI  - Effect of ibuprofen on the efficacy of inferior alveolar nerve block in patients
      with irreversible pulpitis: A meta-analysis.
AB  - The aim of this study was to compare preventive ibuprofen administration to
      placebo on the efficacy of inferior alveolar nerve block in patients with
      irreversible pulpitis. A search was performed in PubMed, Scopus, Web of Science,
      LILACS, BBO, Cochrane Library, SIGLE, and grey literature. The risk of bias was
      evaluated through the Cochrane Collaboration's tool. The quality of evidence was
      assessed using the GRADE approach. Only seven studies remained for the meta
      analysis. Administering ibuprofen before anaesthesia increased the success rate
      of injectable anaesthesia (RR = 1.79; 95% confidence interval (CI) 1.32-2.42; P =
      0.0002) even in cases of symptomatic irreversible pulpitis (RR = 1.55; 95% CI
      1.05-2.29; P = 0.03). The intensity of pain was lower for ibuprofen (standardised
      difference means (SMD) = -3.73; 95% CI -6.43 to -1.04; P = 0.007). Ibuprofen as
      premedication is beneficial for the success of inferior alveolar nerve block.

PMID- 30295008
TI  - Different faces of neurodegeneration.
AB  - This Special Issue comprises nine reviews offering perspectives from the
      development of neurodegeneration in different pathologies to neuronal protection,
      providing new views on the mechanism of neurodegeneration and associated
      processes and a summary of the progress in neuroscience. We hope you find these
      reviews interesting and informative and we thank the authors for these excellent
      contributions to The FEBS Journal.

PMID- 30295009
TI  - The Impact of Nano- and Microstructure on the Stability of Perovskite Solar
      Cells.
AB  - Halide perovskites have emerged recently as a promising candidate for the next
      generation of photovoltaics. Power conversion efficiencies for laboratory-scale
      devices surpass those of established technologies, such as multicrystalline
      silicon. However, perovskite solar cells lose their initial efficiency rapidly
      due to the convolution of several degradation factors, which hinder the process
      of industrialization. In this review, the important role of the nano- and
      microstructure of the perovskite layer in the performance and stability of the
      device are discussed. The defects located predominantly at the grain boundaries
      within the perovskite film and at the interface of the perovskite with the other
      materials can compromise the devices' stability. Thus, lowering the surface and
      interface concentration of defects is a key approach toward long-term stable
      perovskite solar cells.

PMID- 30295010
TI  - Absorptive Hydrogen Scavenging for Enhanced Aromatics Yield During Non-oxidative
      Methane Dehydroaromatization on Mo/H-ZSM-5 Catalysts.
AB  - Addition of Zr metal particles to MoCx /ZSM-5 in interpellet mixtures (2:1 weight
      ratio) resulted in maximum single-pass methane conversion of 27 % for
      dehydroaromatization at 973 K (in significant excess of the equilibrium
      prescribed circa 10 % conversion at these conditions) and a concurrent 1.4-5.6
      fold increase in aromatic product yields due to circumvention of thermodynamic
      equilibrium limitations by absorptive H2 removal by Zr while retaining cumulative
      aromatic product selectivity. The absorptive function of the polyfunctional
      catalyst formulation can be regenerated by thermal treatment in He flow at 973 K,
      yielding above-equilibrium methane conversion in successive regeneration cycles.
      H2 uptake experiments demonstrate formation of bulk ZrH1.75 on hydrogen
      absorption by Zr at 973 K. Cooperation between absorption and catalytic centers
      distinct in location and function enables circumvention of persistent
      thermodynamic challenges in non-oxidative methane dehydrogenation.

PMID- 30295012
TI  - Stimuli-Responsive Supramolecular Hydrogels and Their Applications in
      Regenerative Medicine.
AB  - Supramolecular hydrogels are a class of self-assembled network structures formed
      via non-covalent interactions of the hydrogelators. These hydrogels capable of
      responding to external stimuli are considered to be smart materials due to their
      ability to undergo sol-gel and/or gel-sol transition upon subtle changes in their
      surroundings. Such stimuli-responsive hydrogels are intriguing biomaterials with
      applications in tissue engineering, delivery of cells and drugs, modulating
      tissue environment to promote innate tissue repair, and imaging for medical
      diagnostics among others. This review summarizes the recent developments in
      stimuli-responsive supramolecular hydrogels and their potential applications in
      regenerative medicine. Specifically, various structural aspects of supramolecular
      hydrogelators involved in self-assembly, the role of external stimuli in
      tuning/controlling their phase transitions, and how these functions could be
      harnessed to advance applications in regenerative medicine are focused on.
      Finally, the key challenges and future prospects for these versatile materials
      are briefly described.

PMID- 30295011
TI  - Arterial stiffness mediates the effect of salt intake on systolic blood pressure.
AB  - Accumulating evidence indicates that higher levels of salt intake are associated
      with higher blood pressure levels. The aim of our analysis was to test the
      hypothesis that the effect of urinary sodium excretion (UNaV) on systolic blood
      pressure (SBP) is mediated through estimated glomerular filtration rate (eGFR)
      and arterial stiffness and also to test the direction of the relationship between
      eGFR and arterial stiffness, in both hypertensive and normotensive patients. We
      assessed the potential for connection between UNaV and SBP and mediators (eGFR
      and pulse wave velocity [PWV]) of this relationship using structural equation
      models of data from 1599 adults >=18 years of age and without chronic kidney
      disease who participated in the Third Epidemiologic Study concerning the
      Prevalence of Arterial Hypertension and Cardiovascular Risk in Romania (SEPHAR
      III). In hypertensive patients, the indirect effect, mediated through PWV, of
      UNaV on SBP was 23.9% and 27.7% of the total effect of UNaV on SBP, while in
      normotensive patients the contribution of PWV to the total effect of UNaV on SBP
      was slightly lower (15.9% and 18.3% of the total effect of UNaV on SBP). Taken
      together, our findings support the conclusion that UNaV influences SBP, both
      directly and indirectly, through the effect on PWV.

PMID- 30295013
TI  - Disseminated Trichosporon asahii infection in a patient with acute myeloid
      leukemia.

PMID- 30295014
TI  - Common and distinct components of communication partner training programmes in
      stroke, traumatic brain injury and dementia.
AB  - BACKGROUND: Communication partner training (CPT) programmes for health and care
      staff working with people with the neurologically based communication disorders
      associated with stroke, traumatic brain injury (TBI) and dementia are efficacious
      in improving communication. However, current programmes are lengthy and disorder
      specific, and therefore may not be suitable as staff training tools in
      environments with people with multiple communication disorders, and services with
      a variety of neurological populations. AIMS: To identify common and distinct
      components of CPT programmes for stroke, TBI and dementia in order to determine
      whether there are common delivery methods and content that can be consolidated to
      improve implementation of CPT in health and care services. METHODS & PROCEDURES:
      A qualitative enquiry was used. Four CPT programmes targeting three disorders
      were identified from systematic reviews and literature searches. Programme data
      were recorded onto data sheets from manuals, study articles and supplementary
      materials, and were categorized using the Intervention Taxonomy (ITAX). Content
      analysis and elements of constant comparative analysis were employed to analyse
      the CPT programmes. OUTCOMES & RESULTS: Delivery characteristics were similar
      across all four programmes. All were delivered face to face in either group or
      individual contexts. However, duration varied from 1 to 35 h. Six of the 12
      categories of information provided were common across all programmes, including
      'strategy' 'background to disorder', 'information about communication',
      'information about program', 'negative behaviours to avoid' and 'purpose of
      program'. Programmes differed in the types of skill-building techniques used,
      with the most common being videos (3/4 programmes), discussions (2/4 programmes)
      and trainer demonstrations (2/4 programmes). While strategies provided to trained
      partners targeted similar domains of communication, only 3/96 individual
      strategies were common to all programmes. CONCLUSIONS & IMPLICATIONS: There are
      both common and distinct components in content and delivery methods across CPT
      programmes. Further research is needed to evaluate the distinct components of the
      programmes, to determine which individual strategies are efficacious, and which
      approach to skill-building techniques is most effective. The present study has
      contributed a comprehensive list of programme components, which can form a basis
      for describing and refining CPT programmes in future.

PMID- 30295015
TI  - Multifunctional, Superelastic, and Lightweight MXene/Polyimide Aerogels.
AB  - 2D transition metal carbides and nitrides (MXenes) have gained extensive
      attention recently due to their versatile surface chemistry, layered structure,
      and intriguing properties. The assembly of MXene sheets into macroscopic
      architectures is an important approach to harness their extraordinary properties.
      However, it is difficult to construct a freestanding, mechanically flexible, and
      3D framework of MXene sheets owing to their weak intersheet interactions. Herein,
      an interfacial enhancement strategy to construct multifunctional, superelastic,
      and lightweight 3D MXene architectures by bridging individual MXene sheets with
      polyimide macromolecules is developed. The resulting lightweight aerogel exhibits
      superelasticity with large reversible compressibility, excellent fatigue
      resistance (1000 cycles at 50% strain), 20% reversible stretchability, and high
      electrical conductivity of ~4.0 S m-1 . The outstanding mechanical flexibility
      and electrical conductivity make the aerogel promising for damping, microwave
      absorption coating, and flexible strain sensor. More interestingly, an
      exceptional microwave absorption performance with a maximum reflection loss of 
      45.4 dB at 9.59 GHz and a wide effective absorption bandwidth of 5.1 GHz are
      achieved.

PMID- 30295016
TI  - Combined therapy with osimertinib and afatinib in a lung adenocarcinoma patient
      with EGFR T790M mutation and multiple HER2 alterations after resistance to
      icotinib: A case report.
AB  - Acquired resistance inevitably occurs after initial treatment with first
      generation EGFR-tyrosine kinase inhibitors (TKIs). Several mechanisms have been
      identified, including EGFR T790M mutation and HER2 amplification. Herein, we
      present the case of a patient who progressed on first-generation EGFR-TKIs and
      developed EGFR T790M mutation, HER2 amplification, and HER2 mutation. The
      administration of single-agent osimertinib yielded an inconsistent response, with
      worsened pleural effusion and a reduction to lung metastases, but remarkably, a
      partial response was achieved after four weeks of treatment with combined
      osimertinib and afatinib, with grade 1 rash and grade 2 diarrhea. Our findings
      indicate an overlap of T790M, HER2 amplification, and HER2 mutation, which is
      rarely reported. Moreover, HER2 mutation was identified during the development of
      resistance, suggesting that HER2 mutation may cause resistance to first
      generation EGFR-TKIs.

PMID- 30295017
TI  - Exaggerated health news: association between exaggeration in university press
      releases and exaggeration in news media coverage
AB  - Objective: To determine how often press releases and news articles contain
      exaggeration and to locate its origin in the trajectory from research paper to
      news article. Design: Retrospective quantitative content analysis. Method: We
      analysed press releases on health-related research published by Dutch
      universities and university medical centres in 2015 (n = 129) as well as news
      media articles related to those press releases (n = 185). Results: 20% of press
      releases and 29% of news articles exaggerated the conclusion or causal claim.
      Explicit health advice was, when present, exaggerated in 7% of press releases and
      10% of news articles. When press releases exaggerated the conclusion or causal
      claim, 92% of associated news articles contained the same exaggeration. When the
      conclusion was not exaggerated in the press release, 6% of the news articles was
      exaggerated. The relative chance for exaggerated news associated with exaggerated
      press releases was 16.08 (95% CI: 7.35-35.18). Exaggerated press releases were
      associated with news articles more frequently. The relative chance for news
      articles to be associated with exaggerated press releases vs. a non-exaggerated
      press release was 1.45 (95% CI: 1.02-2.04). Conclusion: Exaggeration in health
      related news is strongly correlated with exaggeration in the original press
      release and occurs in more than 1 in 5 articles. Monitoring and, if necessary,
      improving the accuracy and correctness of academic press releases seem to be
      important measures to improve the quality of health related news. : Conflict of
      interest and financial support: I. Smeets is a columnist with one of the
      newspapers investigated. She was not involved in collecting, coding and analysing
      the relevant data. Additional potential conflicts of interest have been reported
      for this article. ICMJE forms provided by the authors are available online along
      with the full text of this article.

PMID- 30295018
TI  - Nonvolatile Memory Based on Molecular Ferroelectric/Graphene Field Effect
      Transistor.
AB  - Ferroelectric thin films are extensively attractive as next-generation
      nonvolatile memories. Recently, molecular ferroelectrics (MFe), as an emerging
      new class, have been a new research focus because of their desirable
      characteristics such as good solution processability, tunable chemical
      properties, and bio-friendly compositions. However, traditional uniaxial MFe only
      possess one polar axis which greatly limits their application, as it requires
      restricted orientational control in single crystal. To achieve macroscopic
      ferroelectricity and thus fully realize technological advantages of MFe,
      development of multiaxes is imperative to maximize effective polarization in
      specific crystallographic orientations. Herein, we present an early exploration
      on polycrystalline multiaxial MFe thin films of [Hdabco][ReO4] with a two
      dimensional graphene hybrid nonvolatile memory device. The polarization switching
      of MFe is experimentally realized by the nonvolatile modulation of two current
      states in graphene. Such a hybrid device can exhibit large memory window ~35 V
      implying its great potential in memory applications. Hence, by taking the
      advantages of multiple polarization axes of MFe, the low cost and large area
      MFe/graphene hybrid memory manifests new possibilities for the integration of
      these materials as flexible next generation memory devices.

PMID- 30295019
TI  - Carbonylative Synthesis of 3-Substituted Thiochromenones via Rhodium-Catalyzed [3
      + 2 + 1] Cyclization of Different Aromatic Sulfides, Alkynes, and Carbon
      Monoxide.
AB  - We have developed a rhodium-catalyzed carbonylative annulation methodology for
      the direct preparation of thiochromenones. With nonactivated aromatic sulfides
      and terminal alkynes as the substrates, the desired sulfur-containing six
      membered heterocycles were prepared effectively via [3 + 2+1]-type annulation.

PMID- 30295020
TI  - Acid-Induced Gelation of Caseins Glycated with Lactose: Impact of Maillard
      Reaction-Based Glycoconjugation and Protein Cross-Linking.
AB  - During food processing or storage, milk proteins can react with reducing sugars
      via the Maillard reaction (glycation), which may alter their techno-functional
      properties. The aim of this study was to investigate the relationship between
      molecular changes of casein occurring during different stages of the Maillard
      reaction and its acid-induced gelling properties. Therefore, sodium caseinate was
      heated in a dry state at 60  degrees C in the presence of lactose and analyzed
      for structural modifications by determining Amadori compounds (glycoconjugation)
      indirectly as furosine, the total lysine modification, and the extent of protein
      cross-linking. For techno-functional characterization, acid-induced gels were
      prepared by the addition of glucono-delta-lactone and evaluated by measuring pH
      kinetics during gel formation, gel strength, and water holding capacity. The time
      to reach pH 4.6 during the gelation process was significantly delayed with
      increasing extent of the Maillard reaction. Glycation with lactose also led to a
      significant increase in gel strength and water holding capacity. The increase in
      gel stability was rather independent from the amount of sugars covalently bound
      to the proteins during the early phase of the Maillard reaction but strongly
      correlated to the degree of protein polymerization. Small- and medium-sized
      casein oligomers, formed during advanced stages of the Maillard reaction,
      contributed considerably to the formation of stronger gels with higher water
      holding capacity, whereas a sharp increase in the relative amount of the polymer
      fraction observed during prolonged cross-linking processes caused a spontaneous
      destabilization of the gel network. Knowledge about structure-function
      relationships on a molecular level can provide useful information to control food
      texture by raw material quality.

PMID- 30295021
TI  - In Situ Formation of Micropore-Rich Titanium Dioxide from Metal-Organic Framework
      Templates.
AB  - Phase and porosity control in titanium dioxide (TiO2) is essential for the
      optimization of its photocatalytic activity. However, concurrent control over
      these two parameters remains challenging. Here, a novel metal-organic framework
      templating strategy is demonstrated for the preparation of highly microporous
      anatase TiO2. In situ encapsulation of Ti precursor in ZIF-8 cavities, followed
      by hydrolysis and etching, produces anatase TiO2 with a high Brunauer-Emmett
      Teller surface area of 335 m2.g-1 and a micropore surface area ratio of 48%.
      Photocatalytic hydrogen generation catalyzed by the porous TiO2 can reach a rate
      of 2459 MUmol.g-1.h-1. The measured photocatalytic activity is found to be
      positively correlated to the surface area, highlighting the importance of
      porosity control in heterogeneous photocatalysts.

PMID- 30295022
TI  - Carbon-Fiber Microbiosensor for Monitoring Rapid Lactate Fluctuations in Brain
      Tissue Using Fast-Scan Cyclic Voltammetry.
AB  - Recent studies have described a role for lactate in brain energy metabolism and
      energy formation, challenging the conventional view that glucose is the principle
      energy source for brain function. To date, lactate dynamics in the brain are
      largely unknown, limiting insight into function. We addressed this by developing
      and characterizing a lactate oxidase-modified carbon-fiber microelectrode coupled
      with fast-scan cyclic voltammetry. This new tool boasts a sensitivity for lactate
      of 22 +/- 1 nA.mM-1 and LOD of 7.0 +/- 0.7 MUM. The approach has enabled
      detection of rapid lactate fluctuations with unprecedented spatiotemporal
      resolution as well as excellent stability, selectivity, and sensitivity. The
      technology was characterized both in vitro and in vivo at discrete recording
      sites in rat striatum. We provide evidence that striatal lactate availability
      increases biphasically in response to electrical stimulation of the dopaminergic
      midbrain in the anesthetized rat. This new tool for real-time detection of
      lactate dynamics promises to improve understanding of how lactate availability
      underscores neuronal function and dysfunction.

PMID- 30295023
TI  - Organic Media Superwettability: On-Demand Liquid Separation by Controlling
      Surface Chemistry.
AB  - Superwettability involving water affinity has demonstrated prominent advantages
      in oil-water separation. However, superwetting surfaces in nonpolar liquid-polar
      liquid systems are rarely explored for the separation of organic liquids. In this
      work, a protocol of elaborately controlling surface chemistry is presented to
      construct dual superlyophobic surfaces for polar or nonpolar liquids in opposite
      organic media. On two kinds of silver-roughened copper coatings, a polar hydroxyl
      group is subtly integrated with nonpolar perfluoroalkyl chain at the nanoscale.
      Prewetted by one organic liquid, the obtained dual superlyophobic mesh can
      selectively intercept other immiscible organic liquids, realizing high-efficiency
      on-demand separation. In theory, the dual superlyophobic surfaces in organic
      media are strongly dependent on their affinity toward polar liquids and the
      surface roughness. The discovery may promote the development of organic liquid
      related interfacial materials.

PMID- 30295025
TI  - Modeling QCM-D Response to Deposition and Attachment of Microparticles and Living
      Cells.
AB  - Quartz crystal microbalance with dissipation monitoring (QCM-D) is a powerful
      tool for studying adhesion, yet its use for analyzing the deposition of
      microparticles and living cells on surfaces has been hampered by difficulties in
      interpretation. Here we report a new quantitative model of QCM-D response,
      presented as an equivalent acoustic impedance circuit. As an essential feature,
      the particle interaction with surrounding fluid is modeled by relations for a
      freely oscillating rotating and translating sphere in an unbounded fluid, which
      is a valid approximation for microparticles. This helps deduce from the measured
      reponse the parameters pertinent to the contact mechanics. We use the model to
      analyze deposition of different microparticles as well as Pseudomonas fluorescens
      bacteria on several substrates using QCM-D combined with real-time microscopy.
      The parameter space is increased by varying particle type and size, substrate
      surface chemistry and rigidity, and ionic strength of the solution, which allows
      observation of diverse responses and transition from inertial to elastic loading,
      including rarely observed resonant regimes. Ultimately, we find that the model
      describes reasonably well the observed response for different microparticles and
      substrates, as well as for bacteria, and enables extraction of the contact
      characteristics in elastic and mixed loading regimes. It also reveals
      discrepancies between measured and anticipated parameters for large particles.
      The new model can be a useful tool for interpreting and quantifying QCM-D data on
      the adhesion of particles and living cells to surfaces, including time-dependent
      adhesion phenomena.

PMID- 30295024
TI  - Synthesis of Piperine Analogs Containing Isoxazoline/Pyrazoline Scaffold and
      Their Pesticidal Bioactivities.
AB  - In continuation of our program to discover new potential pesticidal agents,
      thirty-one piperine analogs containing isoxazoline/pyrazoline scaffold were
      prepared, and confirmed by infrared spectra, proton/carbon-13 nuclear magnetic
      resonance spectra, and high-resolution mass spectra. The structures of compounds
      VIIb and VIIIc were further determined by 1H-1H COSY spectra. Especially the
      configuration of compound VIIIc was unambiguously confirmed by single-crystal X
      ray diffraction. Their pesticidal activities were evaluated against three serious
      and typically crop-threatening agricultural pests, Tetranychus cinnabarinus
      Boisduval (spider mite), Mythimna separata Walker (Oriental armyworm), and
      Plutella xylostella Linnaeus (diamondback moth). Compounds VIIIb and VIIIc
      exhibited greater than 40-fold more potent acaricidal activity than the lead
      compound piperine against T. cinnabarinus. Notably, compounds VIa-c exhibited
      more pronounced oral toxicity against P. xylostella than toosendanin; compounds
      VIb and VIc displayed more promising growth inhibitory activity against M.
      separata than toosendanin. It demonstrated that the methylenedioxy and
      isoxazoline scaffolds were important for the oral toxicity and growth inhibitory
      activity against P. xylostella and M. separata, respectively; the ethylenedioxy
      and isoxazoline scaffolds were vital for the acaricidal activity against T.
      cinnabarinus. Moreover, compounds VIb, VIIf, and VIIIc showed very low toxicity
      against NRK-52E cells.

PMID- 30295026
TI  - Propensity for Proton Relay and Electrostatic Impact of Protein Reorganization in
      Slr1694 BLUF Photoreceptor.
AB  - Photoreceptor proteins play a vital role in a wide range of light-regulated
      processes. The formation of the light-adapted state of blue light using flavin
      (BLUF) photoreceptors is thought to involve rearrangements of hydrogen-bonding
      networks upon photoexcitation. Free energy simulations with partial charges
      corresponding to relevant ground and excited states of the Slr1694 BLUF domain
      characterize conformations prior to and following photoexcitation. The
      simulations indicate that Trp91 is thermodynamically favored to be in the active
      site, although it is also able to sample conformations outside the active site.
      For experimentally observed conformations of Trp91, Gln50 is thermodynamically
      favored to be oriented for a proton relay bridging Tyr8 and the flavin. When
      Trp91 is rotated such that it can donate a hydrogen bond to Gln50, as observed in
      other BLUF domains, the proton relay is not thermodynamically favored in the
      ground state, providing a possible explanation for the relatively fast photocycle
      of the Slr1694 BLUF domain. Photoexcitation to the locally excited (LE) state of
      the flavin induces the formation of the proton relay if it is not already formed.
      Electrostatically embedded time-dependent density functional theory calculations
      indicate that the proton relay reduces the energy gap between the LE state and
      the charge-transfer (CT) state associated with electron transfer from Tyr8 to the
      flavin. Although the CT state is higher in energy than the LE state prior to
      photoexcitation, the protein environment can reorganize in a manner that
      stabilizes the CT state so that it is lower than the LE state, enabling the LE to
      CT state transition. An electrostatic analysis identifies motions of individual
      residues, such as Arg65, that stabilize electron transfer from Tyr8 to the
      flavin. These conformational changes facilitate the critical proton-coupled
      electron transfer reaction in the BLUF photocycle.

PMID- 30295027
TI  - Nitrogen-Doped Microporous Carbons Derived from Pyridine Ligand-Based Metal
      Organic Complexes as High-Performance SO2 Adsorption Sorbents.
AB  - Heteroatom-doped porous carbons are emerging as platforms for gas adsorption.
      Herein, N-doped microporous carbon (NPC) materials have been synthesized by
      carbonization of two pyridine ligand-based metal-organic complexes (MOCs) at high
      temperatures (800, 900, 1000, and 1100  degrees C). For NPCs (termed NPC-1- T and
      NPC-2- T, where T represents the carbonization temperature), the micropore is
      dominant, pyridinic-N and other N atoms of MOC precursors are mostly retained,
      and the N content reaches as high as 16.61%. They all show high Brunauer-Emmett
      Teller surface area and pore volume, in particular, NPC-1-900 exhibits the
      highest surface areas and pore volumes, up to 1656.2 m2 g-1 and 1.29 cm3 g-1,
      respectively, a high content of pyridinic-N (7.3%), and a considerable amount of
      SO2 capture (118.1 mg g-1). Theoretical calculation (int = ultrafine m062x)
      indicates that pyridinic-N acts as the leading active sites contributing to high
      SO2 adsorption and that the higher content of pyridinic-N doping into the
      graphite carbon layer structure could change the electrostatic surface potential,
      as well as the local electronic density, which enhanced SO2 absorption on carbon
      edge positions. The results show great potential for the preparation of
      microporous carbon materials from pyridine ligand-based MOCs for effective SO2
      adsorption.

PMID- 30295028
TI  - Light-Induced Printing of Protein Structures on Membranes in Vitro.
AB  - Reconstituting functional modules of biological systems in vitro is an important
      yet challenging goal of bottom-up synthetic biology, in particular with respect
      to their precise spatiotemporal regulation. One of the most desirable external
      control parameters for the engineering of biological systems is visible light,
      owing to its specificity and ease of defined application in space and time. Here
      we engineered the PhyB-PIF6 system to spatiotemporally target proteins by light
      onto model membranes and thus sequentially guide protein pattern formation and
      structural assembly in vitro from the bottom up. We show that complex micrometer
      sized protein patterns can be printed on time scales of seconds, and the pattern
      density can be precisely controlled by protein concentration, laser power, and
      activation time. Moreover, when printing self-assembling proteins such as the
      bacterial cytoskeleton protein FtsZ, the targeted assembly into filaments and
      large-scale structures such as artificial rings can be accomplished. Thus, light
      mediated sequential protein assembly in cell-free systems represents a promising
      approach to hierarchically building up the next level of complexity toward a
      minimal cell.

PMID- 30295030
TI  - Terarylenes as Photoactivatable Hydride Donors.
AB  - Terarylene frameworks containing benzothiazole as a photoprecursor of hydride
      donors are presented. We here report on two new scaffolds along with their
      photoreactivity in solution. Through use of selected external oxidants, the
      photogeneration of hydride donors is monitored using UV-visible, NMR, and TEM
      methods. As a proof-of-concept, photogeneration of hydride in the presence of Ag+
      gave rise to the formation of Ag nanoparticles.

PMID- 30295029
TI  - Structural Studies of Amyloid Fibrils by Paramagnetic Solid-State Nuclear
      Magnetic Resonance Spectroscopy.
AB  - Application of paramagnetic solid-state NMR to amyloids is demonstrated, using
      Y145Stop human prion protein modified with nitroxide spin-label or EDTA-Cu2+ tags
      as a model. By using sample preparation protocols based on seeding with preformed
      fibrils, we show that paramagnetic protein analogs can be induced into adopting
      the wild-type amyloid structure. Measurements of residue-specific intramolecular
      and intermolecular paramagnetic relaxation enhancements enable determination of
      protein fold within the fibril core and protofilament assembly. These methods are
      expected to be widely applicable to other amyloids and protein assemblies.

PMID- 30295031
TI  - Characterizing Novel Modifications of a Therapeutic Protein Using Ultra
      Performance Liquid Chromatography-Tandem Mass Spectrometry, Sedimentation
      Velocity Analytical Ultracentrifugation, and Structural Modeling.
AB  - Heterogeneity of biopharmaceutical products is common due to various co- and post
      translational modifications and degradation events that occur during the
      biological production process and throughout the shelf life. Product-related
      variants resulting from these modifications potentially affect a product's
      biological activity and safety, and thus, their detailed structure
      characterization is of great importance for successful development of protein
      therapeutics. Specifically, in this study, two novel low-level product variants
      in a recombinant therapeutic protein were characterized via chromatographic
      enrichment followed by proteolytic digestion and analysis using ultra performance
      liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). One of the variants
      was identified to be the therapeutic protein missing a 61-amino-acid fragment
      from its N-terminus. Consequently, the other variant was found to be the
      therapeutic protein carrying the 61-amino-acid long peptide. Furthermore,
      detailed structure at the modification site of the latter variant was determined
      as that amino group from the protein's N-terminus linked to side chain carbonyl
      carbon at Asp 61 residue of the peptide, based on the complementary information
      from collision induced dissociation and electron transfer dissociation MS/MS
      analysis. Results from sedimentation velocity analytical ultracentrifugation and
      computational structural modeling supported the hypothesis that formation of
      these two variants was a result of protein self-association. In dimeric state,
      the head-to-toe stacking conformation of two therapeutic protein molecules
      allowed spatial closeness between the N-terminus of one molecule and the 61st
      amino acid of the other molecule, resulting in a novel peptide transfer  between
      the two protein molecules.

PMID- 30295032
TI  - ProteomeGenerator: A Framework for Comprehensive Proteomics Based on de Novo
      Transcriptome Assembly and High-Accuracy Peptide Mass Spectral Matching.
AB  - Modern mass spectrometry now permits genome-scale and quantitative measurements
      of biological proteomes. However, analysis of specific specimens is currently
      hindered by the incomplete representation of biological variability of protein
      sequences in canonical reference proteomes and the technical demands for their
      construction. Here, we report ProteomeGenerator, a framework for de novo and
      reference-assisted proteogenomic database construction and analysis based on
      sample-specific transcriptome sequencing and high-accuracy mass spectrometry
      proteomics. This enables the assembly of proteomes encoded by actively
      transcribed genes, including sample-specific protein isoforms resulting from non
      canonical mRNA transcription, splicing, or editing. To improve the accuracy of
      protein isoform identification in non-canonical proteomes, ProteomeGenerator
      relies on statistical target-decoy database matching calibrated using sample
      specific controls. Its current implementation includes automatic integration with
      MaxQuant mass spectrometry proteomics algorithms. We applied this method for the
      proteogenomic analysis of splicing factor SRSF2 mutant leukemia cells,
      demonstrating high-confidence identification of non-canonical protein isoforms
      arising from alternative transcriptional start sites, intron retention, and
      cryptic exon splicing as well as improved accuracy of genome-scale proteome
      discovery. Additionally, we report proteogenomic performance metrics for current
      state-of-the-art implementations of SEQUEST HT, MaxQuant, Byonic, and PEAKS mass
      spectral analysis algorithms. Finally, ProteomeGenerator is implemented as a
      Snakemake workflow within a Singularity container for one-step installation in
      diverse computing environments, thereby enabling open, scalable, and facile
      discovery of sample-specific, non-canonical, and neomorphic biological proteomes.

PMID- 30295033
TI  - Egg White-Derived Tripeptide IRW (Ile-Arg-Trp) Is an Activator of Angiotensin
      Converting Enzyme 2.
AB  - Angiotensin converting enzyme 2 (ACE2) plays beneficial roles in the renin
      angiotensin aldosterone system. Our previous studies indicated that egg white
      derived antihypertensive peptide IRW (Ile-Arg-Trp) could upregulate ACE2 mRNA
      level in mesenteric artery of spontaneously hypertensive rats (SHRs), suggesting
      the potential of IRW as an in vivo ACE2 activator. In this study, the effects of
      IRW on activity and protein expression of ACE2 were investigated. Results
      indicated that IRW activated human recombinant ACE2 with an EC50 value of 7.24 *
      10-5 M. In rat aortic vascular smooth muscle cell line A7r5 cells, IRW treatment
      (50 MUM) significantly increased the expression and activity of ACE2. Oral
      administration of IRW to SHRs upregulated ACE2 protein levels in kidney and
      aorta. Molecular docking study suggested that IRW might activate ACE2 through
      interaction with the subdomain I near the active site through hydrogen bonds.
      Overall, this study established IRW as the first food-derived ACE2 activating
      peptide.

PMID- 30295034
TI  - Intact Human Alpha-Acid Glycoprotein Analyzed by ESI-qTOF-MS: Simultaneous
      Determination of the Glycan Composition of Multiple Glycosylation Sites.
AB  - Alpha-1-acid glycoprotein (AGP) is a highly glycosylated protein from human
      plasma with five N-type glycosylation sites carrying dominantly higher antennary
      structures and thus represents a challenging target for characterization of
      glycan heterogeneity. Here, we show that glycan composition over all five
      glycosylation sites can be determined quantitatively by ESI-qTOF-MS of the intact
      glycoprotein in negative ion mode. We find numerous glycan species extending the
      mass range of the glycoprotein species from 35.0 to 38.5 kDa. The dominant glycan
      compositions contain tri- and tetraantennary structures on all glycosylation
      sites. The mass degeneracy of two fucosyl units versus one sialic acid was
      resolved by treating the sample with sialidase and analyzing the resulting
      desialylated AGP by electrospray ionization-mass spectrometry in positive ion
      mode. The pattern of nonsialylated oligosaccharides was used for interpretation
      of the fully sialylated species using bioinformatics tools. From pooled human
      plasma, we find 90, 101, and 64 different glycan compositions for genetic
      variants ORM1*F1, ORM1*S, and ORM2, respectively. Glycan structures carry
      dominantly between 15 and 16 sialic acids indicating an almost complete
      termination of all antenae with sialic acid. AGP from human plasma samples of
      single individuals was analyzed as desialylated glycoproteins and showed
      variations in fucosylation and in the amount of antennary structures between
      individuals.

PMID- 30295035
TI  - Characterization of the Dynamic Growth of the Nanobubble within the Confined
      Glass Nanopore.
AB  - The evolution of the nanobubble from gas molecules in liquid phase is of
      fundamental interest. However, the lack of sensitive tools hinders the study of
      growth dynamic of the bubble at nanoscale. Here, we employed a confined glass
      nanopore to real-time monitor the dynamics behavior of a single nanobubble
      generated by the reaction between NaBH4 and H2O. By analyzing the characteristic
      ionic current signal, the formation time and growth time of a single nanobubble
      could be estimated as 200 and 21 ms, respectively. Further, the nanopore size has
      been altered to modulate the growth behavior of the nanobubble. The results
      demonstrate the capability of the nanopore for sensitively tracking the behavior
      of single nanobubbles in liquid phase, which provides a powerful method for
      further understanding nanobubble evolution.

PMID- 30295036
TI  - Formation of Phenolic Compounds from d-Galacturonic Acid.
AB  - Aqueous d-galacturonic acid (d-GalA) model systems treated at 130  degrees C at
      different pH values show an intense color formation, whereas other reducing
      sugars, such as d-galactose (d-Gal), scarcely react. GC-MS measurements revealed
      the presence of several phenolic compounds: e.g., 3,8-dihydroxy-2-methyl-4 H
      chromen-4-one (chromone) and 2,3-dihydroxybenzaldehyde (2,3-DHBA). These phenolic
      compounds, especially 2,3-DHBA, possess an intense browning potential and cannot
      be found within heated model solutions of reducing sugars. Investigations
      regarding the formation of these substances show that alpha-ketoglutaraldehyde
      plays an important role as an intermediate product. In addition, MS analysis of
      model systems of norfuraneol in combination with 2,3-DHBA showed the formation of
      oligomers that could also be detected in d-GalA model systems, leading to the
      assumption that, in addition to reductic acid, these compounds are jointly
      responsible for the strong color formation during the heat treatment of d-GalA.

PMID- 30295037
TI  - Evaluating the Benefits of the TimeSlips Creative Storytelling Program for
      Persons With Varying Degrees of Dementia Severity.
AB  - OBJECTIVES: To evaluate the benefits of TimeSlips, a group creative storytelling
      intervention used in residential care settings, on quality of life (QOL),
      interactions with caregivers, and Mini-Mental State Examination (MMSE) scores for
      persons with varying degrees of dementia severity. DESIGN: A mixed-methods
      approach was used weekly over a 6-month period to measure QOL and resident
      caregiver relationships. SETTING: A dementia care unit in Pennsylvania.
      PARTICIPANTS: Twenty-two residents with mild-to-severe dementia. MEASUREMENTS:
      Dementia severity and QOL were assessed using the MMSE and Greater Cincinnati
      Chapter Well-Being Observational Tool. Resident-caregiver interactions were
      analyzed using a modified version of the Quality of Interactions Schedule.
      Semistructured interviews were conducted upon the study's conclusion. RESULTS:
      Quantitatively, participants initially classified with mild-moderate dementia
      were significantly more likely to experience positive benefits compared to those
      initially classified with severe dementia. There were no significant changes in
      dementia severity over time. There was also no change in QOL or resident
      caregiver relationships for those with mild-moderate dementia over time, although
      there was a decrease in certain measures of QOL and resident-caregiver
      relationships for those with severe dementia. Qualitative analysis identified
      consistent benefits for residents with both mild-moderate and severe dementia
      over time. CONCLUSIONS: Mixed-methods analyses helped identify benefits of
      TimeSlips for persons at all levels of dementia severity, but particularly for
      those with milder dementia. Such an observation helps demonstrate how arts-based
      programs like TimeSlips can uniquely benefit people with advanced memory
      impairments and thereby support QOL.

PMID- 30295038
TI  - The Role of Gender in Shame, Hostility, and Aggression Experienced by Caregivers
      for Patients With Dementia.
AB  - The aim of this study was to investigate the differences between male and female
      caregivers for patients with dementia in the way they experience various
      psychosocial parameters such as shame, hostility, and aggression. The sample
      included 55 caregivers of patients with moderate and severe dementia, whereas the
      average age was 51 years. Female caregivers were found to experience
      significantly higher levels of external shame, measured by Other As Shamer scale,
      than male caregivers, t (53) = 2.54, P < .01. A significant difference was also
      found between the female and male caregivers regarding their recorded levels of
      internal shame, measured by Experience of Shame Scale, with female caregivers
      experiencing more internal shame than their male counterparts, t (53) = 2.11, P <
      .01. However, no significant differences were found in hostility and aggression
      between males and females. These results demonstrate the existence of gender
      differences in the levels of shame experienced by care providers for patients
      with dementia.

PMID- 30295039
TI  - In vitro bactericidal activity of 0.6% povidone-iodine eye drops formulation.
AB  - PURPOSE: To evaluate the bactericidal activity of a diluted povidone-iodine
      formulation (0.6%) in comparison with the most used 5% povidone-iodine solution
      ophthalmic preparation. METHODS: In vitro bactericidal activity comparison
      between 0.6% povidone-iodine versus 5% povidone-iodine formulations, against
      these bacteria: Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC
      43300, Staphylococcus epidermidis ATCC 12228, linezolid-resistant Staphylococcus
      epidermidis alpha99 strain, a clinical isolate, Pseudomonas aeruginosa ATCC
      27853, Escherichia coli ATCC 25922. RESULTS: About 0.6% povidone-iodine
      formulation was demonstrated to be faster than 5% povidone-iodine preparation in
      killing Gram-positive as well as Gram-negative bacteria. Against a linezolid
      resistant methicillin-resistant Staphylococcus epidermidis strain, 0.6% povidone
      iodine formulation showed the best antiseptic efficacy requirement of 3-log10
      reduction in bacterial load, if compared with the 5% povidone-iodine formulation.
      CONCLUSION: Our investigation has demonstrated that the more diluted 0.6%
      preparation was more rapidly bactericidal than the 5% povidone-iodine
      formulation, most probably due to the fact that dilution from 5% to 0.6%
      increases the amount of free iodine. While our finding must be confirmed by in
      vivo clinical studies, this fact constitutes an intriguing news for what concerns
      the use of povidone-iodine eye drops in the ocular surface treatment before
      intravitreal injections as well as ophthalmic surgery.

PMID- 30295041
TI  - [Miscellaneous].

PMID- 30295040
TI  - The Accuracy of Continuous Glucose Monitoring and Flash Glucose Monitoring During
      Aerobic Exercise in Type 1 Diabetes.

PMID- 30295042
TI  - [Possibilities for prolonging human lifespan].
AB  - The human lifespan in the developed countries significantly increased, from about
      40 years to 80 years, in the last hundred years. This change is due to multiple
      factors, however, the development of medicine and pharmacological research as
      well as social well-being and social care are primarily important. For aging, the
      attrition of the parts of the whole organism are responsible, which is caused by
      endogenous oxidation processes (free radicals), which can destroy any cells in
      the organism. The injury of the defense or regulatory organ systems (immune
      system, neuroendocrine system) influences the whole organism, causing its decline
      (aging), later complete loss of abilities (death). The organism has built-in
      mechanisms for defence (e.g., antioxidant enzymes), however, their functions are
      not enough in our modern, chemically seriously contaminated age and further
      support is needed. This support is represented by antioxidants, as vitamins A, C,
      and E, resveratrol, and pharmaceuticals as rapamycine and rapalogs, selegiline,
      metformin etc., which have important roles in the increase of lifespan and health
      span. The early start of treatments and the use of pharmaceutical combinations
      seem to be important. The paper introduces our today's' lifespan prolongers and
      discusses their effects as well as points to the ways of future development. Orv
      Hetil. 2018; 159(41): 1655-1663.

PMID- 30295043
TI  - [Modern treatment of metastatic hormone-sensitive prostate cancer].
AB  - The treatment of metastatic prostate cancer can be divided into two
      pathophysiological phases: hormone-sensitive and castration-resistant phases.
      Huggins' observation in the year 1941, which was awarded with the Nobel Prize in
      1966, has a key role in treatment during the hormone-sensitive phase, stating
      that if the testicles are removed, the size of the prostate cancer decreases.
      Inducing androgen deprivation, i.e., testosterone depletion is the basic
      treatment of metastatic prostate cancer that patients have to receive life-long.
      In the past eight years, five new agents have been approved besides docetaxel in
      the treatment of metastatic castration-resistant prostate cancer: sipuleucel-T,
      cabazitaxel, abiraterone, enzalutamide, and radium-223. With the sequential
      application of these agents, significant improvement can be achieved in survival.
      Besides the latest developments, the hormone-sensitive phase has become the focus
      of attention, especially in the treatment of patients with de novo metastases and
      poor prognosis. Many studies have proven the outstanding efficacy of adding early
      docetaxel and abiraterone to androgen deprivation therapy. The authors give a
      detailed overview of clinical studies leading to a paradigm change in treatment
      during the hormone-sensitive phase, and call attention to the difficulties
      encountered in Hungarian practice. Orv Hetil. 2018; 159(41): 1664-1671.

PMID- 30295044
TI  - [Possibilities for residual hearing preservation with Nucleus CI532 Slim Modiolar
      electrode array. Case report].
AB  - During the rehabilitation of hearing-impaired patients, the preservation of
      residual acoustic hearing following cochlear implantation by minimizing the
      implantation trauma allows for improved hearing performance. To achieve this,
      minimally invasive, soft surgery methods and thinner, atraumatic electrodes were
      required. In our present study, we reported a case where Cochlear(r) Nucleus
      CI532 Slim Modiolar electrode was implanted in a patient with residual hearing.
      Our aim was to study the possible preservation of postoperative acoustic residual
      hearing by audiological monitoring. Since childhood, due to her congenital
      hearing loss, she has been wearing a conventional, airborne hearing correction
      device on both ears. Six months before cochlear implantation, we measured the
      progression on both sides of the hearing loss, so we decided to perform cochlear
      implantation. The patient had residual hearing on both ears prior to surgery thus
      the Cochlear(r) Nucleus CI532 Slim Modiolar Implant was used. The minimally
      invasive surgery was performed on the patient's right ear through the round
      window approach. Compared to the preoperative hearing threshold (average 85 dBHL)
      in the 4th postoperative week, an initial hearing threshold progression of 20-25
      dBHL was observed between 0.25 and 1.0 kHz, while of 5-10 dBHL between 2.0-4.0
      kHz. Hearing threshold measured in the 6th month showed a slight progression in
      the range above 1 kHz, but improved by the 12th month, to the results achieved at
      the 4th week. The effects of cochlear implantation on residual hearing have been
      studied in numerous studies, in which several key surgical and technical factors
      have been identified. Nucleus CI532 is a Slim Modiolar electrode profile that is
      close to the modiolus, so it is expected to have a lower endocochlear
      hydrodynamic load since it lies in the covering of the osseus spiral lamina, thus
      less influencing the dynamics of the basilar membrane. However, the perimodiolar
      location of the electrode array allows the adjacent nerve elements of the spiral
      ganglion to be stimulated with a lower electrical intensity and a reduced surface
      that may be neuroprotective. Preservation of acoustic residual hearing following
      cochlear implantation improves the patient's speech perception and the sound
      localization skills, particularly in difficult circumstances. Long-term residual
      hearing preservation may also be of great importance in the subsequent
      feasibility for regenerative procedures and drug treatments. Orv Hetil. 2018;
      159(41): 1680-1688.

PMID- 30295046
TI  - Technological Support to Intensive Insulin Therapy by a Novel Smartphone
      Application in Young Adults With Type 1 Diabetes: One Center's Experience.

PMID- 30295045
TI  - [Follow-up study of extremely low birth weight preterm infants to preschool age
      in the light of perinatal complications].
AB  - INTRODUCTION: Owing to the rapid progress of the medical science and technology,
      the chances of survival of the extremely low birth weight (<1000 g) preterm
      babies have dramatically improved. Nevertheless, the research findings on their
      long-term developmental outcome are inconsistent. AIM: Our study has attempted to
      contribute to the understanding of the developmental mechanisms in the extremely
      low birth weight preterm infants and to the prediction of the developmental
      outcomes taking into account of the risk factors of development. METHOD: 34
      preterm children who were free of any major central nervous system injury were
      followed up from one to 5-6 years of age. The psychomotor development of the
      infants was assessed at 1 and 2 years of age and, at 5-6 years of age,
      intelligence tests were administered to the children. Perinatal and environmental
      factors were included in the data analysis. RESULTS: The extremely low birth
      weight preterm children as a group displayed no developmental delay at any of the
      measurement points. The mean developmental quotients were 98.6 and 106.6 at ages
      1 and 2 years, respectively. At 5-6 years of age, the mean verbal IQ was 101.4,
      while the mean performance IQ was 92.9. Behind the group means there was a wide
      range of individual variations. The most powerful contributors to the
      developmental outcomes were birth weight, bronchopulmonary dysplasia, intra
      uterine growth retardation, gender, and maternal education. The girls had a
      significant advantage over the boys in language development. Verbal intelligence
      was hampered by intracranial hemorrhage, while intrauterine growth restriction
      had a similar effect on the performance IQ. CONCLUSIONS: Our results suggest that
      even the extremely preterm infants may have rather good chances of satisfactory
      mental development. However, the individual developmental prospects are
      influenced by a great number of domain-specific risk- and protective factors.
      Although at a group-level, infant psychomotor development is a significant
      predictor of later intelligence quotient, the rate of development may change at
      any age. The phenomenon of "moving risk" underscores the importance of the long
      term follow-up of preterm infants. Orv Hetil. 2018; 159(41): 1672-1679.

PMID- 30295048
TI  - Burnout, perceived stress, and empathic concern: differences in female and male
      Millennial medical students.
AB  - The 'Millennial' generation faces medical education learning environment
      challenges differently. We explore gender differences in burnout, perceived
      stress, and empathic concern in third-year medical students. A sample size of 654
      third-year medical students completed an annual survey over 6 years. Survey items
      included: the Maslach Burnout Inventory-Student Scale (MBI-SS), Interpersonal
      Reactivity Index (IRI), and Perceived Stress Scale (PSS). We examined demographic
      differences using independent sample t-tests and performed a two-way ANOVA to
      test for potential interactions. Female students were more likely to have higher
      empathic concern compared to male students (IRI) (20.9+/-3.9 versus 19.1+/-4.1,
      p<0.001), and reported more personal distress (IRI) (9.0+/-4.4 versus 7.6+/-3.8,
      p<0.001), emotional exhaustion (MBI-SS) (15.6+/-5.9 versus 14.4+/-5.9, P<0.013),
      and perceived stress (PSS) (17.3+/-6.1 versus 15.2+/-6.7, p<0.001). Male students
      were more likely to have cynicism (MBI-SS) and lower professional efficacy (MBI
      SS) scores. Results of multivariate analyses yielded no significant interactions
      between gender, age, and ethnicity. Self-reported experiences of burnout and
      stress differed in male and female third-year medical students. Burnout and
      perceived stress scores while statistically significant were small. These
      findings suggest that support services should be made broadly available to all
      medical students, but should be targeted to the specific needs of male and female
      students.

PMID- 30295047
TI  - Perceived Behavioral Control as a Key to Integrative Medicine.
AB  - The purpose of the present study was to identify the factors that are the
      strongest predictors of intentions and use of integrative medicine approaches in
      clinical practice. Ajzen's theory of planned behavior was used to guide our
      examination of these questions. Health care professionals exposed to a Veterans
      Health Administration program (N = 288) who completed survey instruments prior to
      and immediately after the program and 3 months later were the participants for
      this study. Findings suggest that the theory of planned behavior performs
      reasonably well in explaining our data showing the integration of integrative
      medicine approaches into clinical practice. We found that self-efficacy to use
      integrative health approaches and perceived preparedness to discuss
      nonpharmaceutical approaches with patients were the strongest predictors of
      intentions to use integrative health approaches and self-reported change in
      clinical practice. The implications of these findings are discussed.

PMID- 30295049
TI  - Use of two long-acting injectable antipsychotics for treatment-resistant
      schizophrenia.

PMID- 30295051
TI  - Koro and denial of genital ownership.

PMID- 30295050
TI  - Developing informed consent materials for non-English-speaking participants: An
      analysis of four professional firm translations from English to Spanish.
AB  - BACKGROUND/AIMS:: An increasing body of research is being conducted with non
      English-speaking subjects. Study-related materials, including those essential for
      obtaining informed consent, must often be translated from English into other
      languages. In this study, we sought to examine the types of issues that may arise
      when consent materials are translated from English to Spanish. METHODS:: Drawing
      on expertise from five individuals associated with our research team, four of
      whom are native Spanish speakers of different dialects of Spanish, we crafted
      translations of our own consent materials for biobanking using a rigorous, multi
      step process involving both forward and back translation. We then systematically
      compared our translations to those produced by four professional translation
      firms to identify potential concerns in our own and the professional
      translations. RESULTS:: We identified three primary types of problems of
      relevance for researchers conducting studies where translation of written
      information is required. These included nonequivalent registers (in particular,
      the introduction of more complicated language), errors of omission (reducing the
      clarity of the information), and changes that altered the substantive meaning of
      the information. CONCLUSION:: Our findings highlight the importance of working
      with translators who not only possess "textbook" knowledge of both languages but
      also an appreciation of the sociocultural factors that affect how people
      interpret and understand meaning. Moreover, translators who have a basic
      understanding of research are more likely to accurately convey essential research
      concepts. We describe a series of steps researchers can take that may help to
      improve the quality of translated materials.

PMID- 30295052
TI  - A case of psychogenic Parkinsonism: Late age of onset should not be a barrier to
      make the diagnosis.

PMID- 30295053
TI  - Rapidly discriminating culture-negative urine specimens from patients with
      suspected urinary tract infections by UF-5000.
AB  - AIM: A rapid and reliable method of discriminating such specimens would be very
      useful. MATERIALS & METHODS: We analyzed 566 urine specimens from patients with
      suspected urinary tract infections using a fully automated urine particle
      analyzer (UF-5000) and evaluated its performance for culture-negative urine
      specimens. RESULTS: Using the algorithm cutoff values of bacteria less than
      30/MUl and/or white blood cell less than 200/MUl, we obtained a sensitivity of
      97.8%, a specificity of 74.6%, a positive predictive value of 46.9%, a negative
      predictive value of 99.3%, an agreement of 78.9% with the culture method and
      reduced 61% unnecessary urine culture. Regarding the discrimination of bacterial
      Gram groups, 67.7% (63/93) of cases were correctly analyzed using the UF-5000
      bacteria information, with a Cohen's kappa concordance coefficient of 0.775 (chi2
      = 31.65, p < 0.001). CONCLUSION: The performance of UF-5000 for rapidly
      discriminating culture-negative specimens was quite acceptable for clinical use.

PMID- 30295054
TI  - Psychometric Properties of the Dutch Strengths and Difficulties Questionnaire
      (SDQ) in Adolescent Community and Clinical Populations.
AB  - This study assessed the factor structures of the Strengths and Difficulties
      Questionnaire (SDQ) adolescent and parent versions and their measurement
      invariance across settings in clinical ( n = 4,053) and community ( n = 962)
      samples of Dutch adolescents aged 12 to 17 years. Per SDQ version, confirmatory
      factor analyses were performed to assess its factor structure in clinical and
      community settings and to test for measurement invariance across these settings.
      The results suggest measurement invariance of the presumed five-factor structure
      for the parent version and a six-factor structure for the adolescent version.
      Furthermore, evaluation of the SDQ scale sum scores as used in practice,
      indicated that working with sum scores yields a fairly reasonable approximation
      of working with the favorable but less easily computed factor scores. These
      findings suggest that adolescent- and parent-reported SDQ scores can be
      interpreted using community-based norm scores, regardless of whether the
      adolescent has been referred for mental health problems.

PMID- 30295055
TI  - A Reformulated Architecture of Cognitive Risks for Psychopathology: Common and
      Specific Dimensions and Links to Internalizing Outcomes in Adolescence.
AB  - Multiple cognitive risk products (dysfunctional attitudes [DA], negative
      inferential style [NIS], self-criticism, dependency, rumination) predict
      internalizing disorders; however, an optimal structure to assess these risks is
      unknown. We evaluated the fit, construct validity, and utility of a bifactor,
      single, and correlated factor model in a community sample of 382 adolescents (age
      11-15 years; 59% female). The bifactor, hierarchical single, and correlated
      factor models all fit well. The bifactor model included a common factor ( c),
      capturing covariance across all cognitive risk measures, and specific latent
      factors for DA, NIS, dependency and rumination. Construct validity of these
      factor structures was evaluated with external validators, including depression
      and anxious arousal (AA) symptoms, positive affect (PA) and negative affect (NA),
      and onset of depression diagnostic onset over 2 years. C was associated with
      higher depression, NA, and AA; lower PA; and predicted depressive episodes.
      Hierarchical single and correlated factor models also related to external
      validators.

PMID- 30295056
TI  - Can one spring back from psychosis? The role of resilience in serious mental
      illness.

PMID- 30295057
TI  - The Capture Gap: Implantable Cardioverter-Defibrillator Quality of Life.
AB  - We aimed to compare salient characteristics and antecedents of quality of life
      (QOL) in adolescents and young adults with implantable cardioverter
      defibrillators (ICDs) from qualitative methods with quantitative measurement of
      QOL and correlations between QOL (PedsQL) and measured participant
      characteristics. Concurrent parallel mixed methods design was used to collect
      survey data from the PedsQL electronic health record, demographic questionnaire,
      and semistructured interview data. A convenience sample of 16 individuals with
      ICDs, aged 13 to 25 years, was obtained from a tertiary pediatric facility.
      Overall QOL and subdomains of physical, psychosocial, and academic/work were
      examined by PedsQL and visual analog scale. Select demographics were collected to
      develop a participant profile. Females with ICDs appear to be at risk of poor QOL
      given some unknown factors. Financial status of the individual and the family was
      positively related to QOL. For new ICD persons involved in physical activities
      that must be stopped, peer support appears to improve QOL.

PMID- 30295058
TI  - Correlated Trait-Correlated Method Minus One Analysis of the Convergent and
      Discriminant Validity of the Conners 3 Short Forms.
AB  - This study used the correlated trait-correlated method minus one model to examine
      the convergent and discriminant validity of the scales of the Conners 3 Short [C
      3 (S)]. The C 3 (S) scales in the analysis were inattention (IN),
      hyperactivity/impulsivity (HY), learning problems (LP; learning
      problems/executive functioning from the teacher version), aggression (AG), and
      peer relations (PR, only for parent and teacher versions). A total of 529
      adolescents and children (75% males, mean age = 11.75 years, SD = 2.97 years)
      provided self-ratings, and were also rated by their mothers and teachers. The
      findings indicated no support for the convergence of IN and HY across the three
      respondents. In contrast, there was convergence for LP, AG, and PR. There was
      support for the discriminant validity of the traits, except between IN and HY.
      The findings are discussed in relation to the convergent and discriminant
      validity of the C 3 (S) measures, and the clinical use of the C 3 (S).

PMID- 30295059
TI  - Study of lamina cribrosa depth and optic nerve in patients with spontaneous
      intracranial hypotension.
AB  - PURPOSE: The aim of this study is to analyze the lamina cribrosa depth and to
      study the optic nerve in patients with spontaneous intracranial hypotension.
      METHODS: A total of 10 eyes of the patients with spontaneous intracranial
      hypotension with unknown etiology (study group) and 10 eyes of healthy patients
      without any ophthalmological or neurological pathologies (control group) were
      included. The subjects were submitted to ophthalmological examination with the
      evaluation of visual acuity, spherical equivalent, applanation tonometry,
      pachymetry, axial length, retinography, computerized static perimetry (Humphrey
      30-2 SITA-Standard), and OCT Spectralis with enhanced depth image, to calculate
      the depth of the anterior surface of the lamina cribrosa and to measure the nerve
      fiber layer thickness of the optic nerve. All of these parameters were compared
      between the two groups. RESULTS: Mean anterior surface of the lamina cribrosa
      depth was 447.96 +/- 118.51 (313.30-632.0) MUm for the spontaneous intracranial
      hypotension group and 292.56 +/- 40.71 (247-387) MUm for the control group, with
      a statistically significant difference between them (p = 0.001). The thickness of
      the nerve fiber layer did not differ significantly in the temporal (p = 0.94),
      nasal (p = 0.173), superior (p = 0.41), central (p = 0.36) or inferior (p = 0.5)
      sectors. Four eyes of patients with spontaneous intracranial hypotension showed a
      marked reduction in the temporal nerve fiber layer. Pachymetry (p = 0.16), axial
      length (p = 0.71), and intraocular pressure (p = 0.6) did not differ
      significantly between groups, whereas spherical equivalent (p = 0.03) was
      significantly different. Visual fields were normal in both groups. CONCLUSION:
      The translaminar gradient is determinant in the structure of the lamina cribrosa.
      Low intracranial pressure associated with a high translaminar gradient leads to
      an increased lamina cribrosa depth similar to that observed in glaucoma patients.

PMID- 30295060
TI  - Mobile Complex Care Plans to Enhance Parental Engagement for Children With
      Medical Complexity.
AB  - Care plans can reduce care fragmentation for children with medical complexity
      (CMC); however, implementation is challenging. Mobile health innovations could
      improve implementation. This mixed methods study's objectives were to (1)
      evaluate feasibility of mobile complex care plans (MCCPs) for CMC enrolled in a
      complex care program and (2) study MCCPs' impact on parent engagement, parent
      experience, and care coordination. MCCPs were individualized, updated quarterly,
      integrated within the electronic health record, and visible on parents' mobile
      devices via an online portal. In 1 year (September 1, 2016, to August 31, 2017),
      94% of eligible patients (n = 47) received 162 MCCPs. Seventy-four percent of
      parents (n = 35) reviewed MCCPs online. Forty-six percent of these parents (n =
      16) sent a follow-up message, and the care team responded within 8 hours (median
      time = 7.2 hours). In interviews, parents identified MCCPs as an important
      reference and communication tool. MCCPs for CMC in a complex care program were
      feasible, facilitated parental engagement, and delivered timely communication.

PMID- 30295061
TI  - Construction and characterization of an OmpH-deficient mutant of Pasteurella
      multocida strain X-73.
AB  - A capsule-defective mutant strain PBA129 of Pasteurella multocida was constructed
      by electroporation of phagemid containing the coding region of the antisense RNA
      of the ompH gene into the wild type strain X-73 (serovar A:1) of P. multocida.
      The pathogenicity and protective potency of the mutant against homologous and
      heterologous challenge in mice and chickens were characterized. Greyish colonies
      of the mutant, indicating lower capsule thickness, on selective dextrose starch
      agar were observed under an obliquely transmitted light stereomicroscope and
      compared to iridescent colonies of the wild type strain X-73. Strain PBA129 had
      lower capsule thickness than the wild type strain as observed with an electron
      microscope. Strain PBA129 was apparently attenuated, as mice and chickens
      inoculated with the bacteria at 108 CFU survived. Protection was observed in both
      mice and chickens inoculated with strain PBA129 upon challenge exposure to avian
      P. multocida strains X-73 and P-1059 (serovar A:3), respectively. In conclusion,
      the mutant strain PBA129 of P. multocida strain X-73 was completely attenuated,
      and it was possible to induce sufficient protection against avian P. multocida
      strains.

PMID- 30295062
TI  - Risk of probable posttraumatic stress disorder in patients with trigeminal
      neuralgia.
AB  - The object of this study was to reveal the occurrence, risk factors and prognosis
      of posttraumatic stress disorder (PTSD) in patients with trigeminal neuralgia
      (TN). Adult patients who were diagnosed with TN were prospectively collected from
      our neuroscience center. Among the 103 patients recruited, thirty (29.1%)
      participants were identified as probable PTSD cases measured with PTSD Checklist
      for DSM-5 (PCL-5). Compared with patients without PTSD, patients with probable
      PTSD were more likely to be female, have severe pain intensity, be with severely
      interfered general activities, be with more intense depression and anxiety, and
      be more habitually using maladaptive coping strategies. Logistic regression
      analysis showed female sex, severe pain intensity, anxiety and depression
      predicted probable PTSD. In the 28 patients who were initially identified as
      probable PTSD and had 6-month follow-up data, 21 reported complete pain relief
      and 4 reported partial pain relief. Fifteen of the patients who experienced
      complete pain relief recovered from probable PTSD. Our work indicated that PTSD
      can develop among patients with TN. Complete pain relief through surgical
      treatments can help most patients with probable PTSD recover, however,
      psychological support is advised for those who are still obsessed by mental
      disorders even after pain relief.

PMID- 30295063
TI  - Comparison of two biometers: A swept-source optical coherence tomography and an
      optical low-coherence reflectometry biometer.
AB  - PURPOSE: The technological improvements in optical biometers have made cataract
      surgery evolve to the level of refractive surgery. This study assessed the
      correlation and agreement between a biometer using swept-source optical coherence
      tomography technology (IOLMaster 700; Carl Zeiss Meditec, Jena, Germany) and a
      biometer using optical low-coherence reflectometry (Lenstar; Haag Streit, Koeniz,
      Switzerland). PROCEDURES: Optical biometric measurements were taken with the
      IOLMaster 700 and the Lenstar on 129 eyes of 129 patients referred for cataract
      surgery. We compared biometric data (axial length, mean keratometry, central
      pachymetry, anterior chamber depth, lens thickness, and horizontal white-to-white
      measurement) and the emmetropic intraocular lens power calculated with SRK/T and
      Haigis formulas. Correlation and agreement for these parameters were evaluated.
      RESULTS: Only anterior chamber depth measurements (3.05 +/- 0.07 vs 3.07 +/-
      0.07, p < 0.001) and the white-to-white measurement (11.97 +/- 0.07 vs 12.06 +/-
      0.07, p < 0.001) differed significantly between the machines. Correlations and
      agreements were excellent, with perfect agreement for axial length measurement (
      r = 1, intraclass correlation coefficient = 1). Emmetropic intraocular lens power
      did not differ between devices with SRK/T formula (20.94 +/- 0.51 vs 20.92 +/-
      0.50, p = 0.51). With Haigis formula, there was a statistically significant
      difference (21.04 +/- 0.52 vs 20.84 +/- 0.52, p < 0.001). CONCLUSION: This study
      suggests that there is a very high correlation and agreement for the biometric
      measurements and calculation of intraocular lens implant power with the SRK/T
      formula.

PMID- 30295064
TI  - A new dimeric alkylresorcinol from the stem barks of Swintonia floribunda
      (Anacardiaceae).
AB  - From an EtOAc-soluble fraction of the stem barks of Swintonia floribunda
      (Anacardiaceae), one new dimeric alkylresorcinol named integracin E (1), together
      with 4 known compounds (2-5) were isolated. Their chemical structures were
      elucidated based on the spectroscopic data interpretation. The absolute
      configuration of 1 was determined by the specific rotation analysis of its acid
      catalyzed hydrolysis product. Compound 1 showed potent tyrosinase inhibitory
      activity with an IC50 value of 48.2 MUM.

PMID- 30295065
TI  - First look into the eye.
AB  - PURPOSE: Until Helmholtz's discovery of the ophthalmoscope, it was not possible
      to visualize the posterior pole of the eye in a living subject. The aim of this
      work is to emphasize the importance of the invention of the ophthalmoscope
      because the new era in ophthalmology began with it. METHODS: Available literature
      concerning this topic was studied, especially by getting in contact with
      institutes for history of medicine as well as medico-historians in Germany and
      other countries. RESULTS: Hermann von Helmholtz, German physician and physicist,
      presented and published his invention of the ophthalmoscope in 1851. Albrecht von
      Graefe was the first to use ophthalmoscope routinely. He said: 'Helmholtz has
      opened a new world to us'. The first ophthalmoscope was not easy to use. Some
      ophthalmologists even thought that ophthalmoscopy is harmful for the eye,
      particularly for a diseased eye. First, it was used in Germany (A von Graefe),
      Austria (E Jager), and Netherlands (FC Donders). In England, it was used only at
      Moorfields till 1855 (W Bowman). At the First International Congress of
      Ophthalmology in Brussels 1857, the importance of ophthalmoscopy was stressed. FC
      Donders said that every view with the ophthalmoscope into the living eye was a
      new discovery. Among retinal diseases, first were discovered pigment retinopathy
      (FC Donders) and retinal detachment (A Coccius) in 1853. CONCLUSION: Helmholtz
      inaugurated modern era in ophthalmology with his magnificant instrument which
      revolutionized the development of ophthalmology. Von Graefe popularized it.
      Because of the new findings, ophthalmology was definitely separated from surgery
      in the middle of 19th century.

PMID- 30295066
TI  - Comparing the Nonlinear Dynamic Acoustic Parameters of Healthy Adult and
      Pediatric Voices.
AB  - OBJECTIVES:: The aims of this study were to compare nondysphonic adult and
      pediatric voices using linear and nonlinear acoustic parameters and to evaluate
      the ability of adult spectrum convergence ratio (SCR) and rate of divergence
      (ROD) reference values to correctly identify a pediatric voice type as periodic
      or aperiodic. METHODS:: Twenty adult and 36 pediatric nondysphonic voice samples
      were collected and analyzed using linear and nonlinear acoustic parameters.
      Absence of voice disorder was confirmed using perceptual acoustic and spectral
      analysis. Mean values for jitter, shimmer, SCR, and ROD were compared between
      adults and children, across specific age groups, and within genders. Using adult
      reference values for SCR and ROD, samples were classified as primarily periodic
      or aperiodic and typed using spectral analysis. Rates of accurate typing were
      also compared between subject groups. RESULTS:: Overall, jitter and shimmer were
      similar among the adult and pediatric age groups. ROD was significantly different
      among the 3 pediatric and 1 adult group; the pediatric age groups were similar to
      one another. Adult SCR was also significantly different from all of the pediatric
      age groups. In adult men, ROD and SCR were significantly different from all of
      the pediatric age groups; the pediatric age groups were similar to one another.
      In female subjects, ROD was significantly different among all age groups. The ROD
      and SCR reference values were significantly better at categorizing adult voice
      types compared with pediatric voice types. CONCLUSIONS:: In healthy subjects, SCR
      and ROD have discriminatory power for identifying adult versus pediatric voices,
      while jitter and shimmer cannot differentiate between the 2 groups. However, age-
      and gender-specific pediatric reference values must be determined to accurately
      classify voice types using SCR and ROD.

PMID- 30295067
TI  - Effect of Preanalytic Variables on an Automated PTEN Immunohistochemistry Assay
      for Prostate Cancer.
AB  - CONTEXT.-: Phosphatase and tensin homolog (PTEN) is a promising prognostic and
      potentially predictive biomarker in prostate cancer. OBJECTIVE.-: To assess the
      effects of preanalytic variables on an analytically validated and fully automated
      PTEN immunohistochemistry assay. DESIGN.-: PTEN immunohistochemistry was
      performed on Ventana immunostaining systems. In benign prostate tissues,
      immunostaining intensity across variable conditions was assessed by digital image
      analysis. In prostate tumor tissues, immunostaining was scored visually. RESULTS.
      : Delay of fixation for 4 hours or longer at room temperature or 48 hours or
      longer at 4 degrees C and duration of formalin fixation did not significantly
      alter immunostaining intensity. Intensity of staining was highest in 10% formalin
      compared with other fixatives. Tumor tissues with PTEN loss processed using
      protocols from 11 academic institutions were all evaluable and scored
      identically. PTEN immunostaining of needle biopsies where tissue blocks had been
      stored for less than 10 years was more frequently scored as nonevaluable compared
      with blocks that had been stored for 10 years or longer. This effect was less
      evident for radical prostatectomy specimens, where low rates of nonevaluable
      staining were seen for 23 years or more of storage. Storage of unstained slides
      for 5 years at room temperature prior to immunostaining resulted in equivalent
      scoring compared with freshly cut slides. Machine-to-machine variability assessed
      across 3 Ventana platforms and 2 institutions was negligible in 12 tumors, and
      platform-to-platform variability was also minor comparing Ventana and Leica
      instruments across 77 tumors (kappa = 0.926). CONCLUSIONS.-: Automated PTEN
      immunostaining is robust to most preanalytic variables in the prostate and may be
      performed on prostate tumor tissues subjected to a wide range of preanalytic
      conditions. These data may help guide assay development if PTEN becomes a key
      predictive biomarker.

PMID- 30295068
TI  - Elimination of Autofluorescence in Archival Formaldehyde-Fixed, Paraffin-Embedded
      Bone Marrow Biopsies.
AB  - CONTEXT.-: High levels of autofluorescence in bone marrow tissue constitute a
      major obstacle to immunofluorescence analysis of bone marrow biopsies. OBJECTIVE.
      : To present a simple, efficient method to eliminate autofluorescence in bone
      marrow biopsies. DESIGN.-: Autofluorescence of paraffin bone marrow tissues was
      examined in different hematologic disorders with confocal laser scanning
      microscopy. Strong autofluorescence was observed in primary myelofibrosis and
      acute leukemia with reticulin myelofibrosis in 488-nm and 561-nm channels. To
      eliminate autofluorescence, AutoFluo Quencher was used on bone marrow sections
      with different incubation times. The effects of AutoFluo Quencher on
      immunofluorescence analysis of bone marrow biopsies was tested using antibodies
      tagged with different fluorophores. RESULTS.-: AutoFluo Quencher thoroughly
      eliminated the strong autofluorescence of bone marrow but did not decrease the
      intensity of fluorophores, leaving the specific signals of target proteins
      clearly visible. CONCLUSIONS.-: This study presents a simple, efficient method to
      eliminate autofluorescence in bone marrow paraffin tissue, and it opens the way
      to better results in the immunofluorescence analysis of bone marrow biopsies.

PMID- 30295069
TI  - Diagnostic Accuracy of Reflectance Confocal Microscopy Skin.
AB  - CONTEXT.-: Histopathology is the current standard to diagnose skin disease.
      However, biopsy may not always be feasible, such as in patients with multiple
      nevi, a patient with a lesion on an aesthetically significant site, or in
      children. Recently, noninvasive techniques, including reflectance confocal
      microscopy (RCM), optical coherence tomography, and Raman spectroscopy, have
      enabled dermatologists to manage skin lesions in real time without the need for
      biopsy. OBJECTIVE.-: To report the updated diagnostic accuracy of RCM for
      equivocal skin lesions. DESIGN.-: In this study, we retrospectively reviewed our
      data of clinically suspicious lesions from 2010 to 2017 that were evaluated by
      RCM. RESULTS.-: Our results showed an overall sensitivity of 98.2% and
      specificity of 99.8%. CONCLUSIONS.-: In conclusion, RCM is a noninvasive real
      time tool with the potential to diagnose skin lesions with high accuracy and
      without biopsy.

PMID- 30295070
TI  - Artificial Intelligence-Based Breast Cancer Nodal Metastasis Detection.
AB  - CONTEXT.-: Nodal metastasis of a primary tumor influences therapy decisions for a
      variety of cancers. Histologic identification of tumor cells in lymph nodes can
      be laborious and error-prone, especially for small tumor foci. OBJECTIVE.-: To
      evaluate the application and clinical implementation of a state-of-the-art deep
      learning-based artificial intelligence algorithm (LYmph Node Assistant or LYNA)
      for detection of metastatic breast cancer in sentinel lymph node biopsies.
      DESIGN.-: Whole slide images were obtained from hematoxylin-eosin-stained lymph
      nodes from 399 patients (publicly available Camelyon16 challenge dataset). LYNA
      was developed by using 270 slides and evaluated on the remaining 129 slides. We
      compared the findings to those obtained from an independent laboratory (108
      slides from 20 patients/86 blocks) using a different scanner to measure
      reproducibility. RESULTS.-: LYNA achieved a slide-level area under the receiver
      operating characteristic (AUC) of 99% and a tumor-level sensitivity of 91% at 1
      false positive per patient on the Camelyon16 evaluation dataset. We also
      identified 2 "normal" slides that contained micrometastases. When applied to our
      second dataset, LYNA achieved an AUC of 99.6%. LYNA was not affected by common
      histology artifacts such as overfixation, poor staining, and air bubbles.
      CONCLUSIONS.-: Artificial intelligence algorithms can exhaustively evaluate every
      tissue patch on a slide, achieving higher tumor-level sensitivity than, and
      comparable slide-level performance to, pathologists. These techniques may improve
      the pathologist's productivity and reduce the number of false negatives
      associated with morphologic detection of tumor cells. We provide a framework to
      aid practicing pathologists in assessing such algorithms for adoption into their
      workflow (akin to how a pathologist assesses immunohistochemistry results).

PMID- 30295071
TI  - Immune keratitis: An unusual primary presentation of neuro-Behcet's disease.
AB  - A 19-year-old Nepalese male presented with complaints of bilateral ocular
      discomfort, photophobia, watering, and redness for 1 week. Visual acuity was 6/12
      and 6/60 in the right and left eye, respectively. On biomicroscopic examination,
      presence of peripheral stromal infiltrates with conjunctival follicles was noted;
      infiltrates progressed to involve central cornea with further decrease in vision
      over next few days. After ruling out infectious keratitis, detailed systemic
      examination and laboratory investigations were diagnostic of neuro-Behcet's
      disease. Patient responded to systemic steroidal and immunosuppressive therapy
      characterized by corneal healing and visual acuity improvement to 6/6 and 6/9.
      Although rare, but neuro-Behcet's disease can primarily present as bilateral
      immune keratitis and every case of bilateral keratitis needs early systemic
      evaluation after ruling out infective etiologies.

PMID- 30295072
TI  - Phytosterols in supplements containing Serenoa repens: an example of variability
      of active principles in commercial plant based products.
AB  - Phytosterols are one of the bioactive components responsible for the beneficial
      effects of Serenoa repens in Benign Prostate Hyperplasia. The aim of this study
      was to verify the actual variability of the phytosterols content in supplements
      containing serenoa, in order to provide useful elements to check the
      effectiveness of these preparations. The amount of campesterol, stigmasterol and
      beta-sitosterol were determined by gas-chromatography in commercial raw materials
      and supplements containing serenoa in association or not with other botanicals.
      The experimental data were used to calculate amounts of phytosterols for
      recommended daily dose. The overall results of this study show an extreme
      variability in the content and also in the amounts per daily dose of phytosterols
      of the examined supplements (both mono/multi components). These data confirm that
      the characterization of serenoa based supplements is insufficient to ensure
      comparable effects between different products.

PMID- 30295073
TI  - GC-EIMS analysis, antifungal and anti-aflatoxigenic activity of Capsicum chinense
      and Piper nigrum fruits and their bioactive compounds capsaicin and piperine upon
      Aspergillus parasiticus.
AB  - GC-EIMS analysis, antifungal- and anti-aflatoxigenic activities of the ethanolic
      extract of Capsicum chinense and Piper nigrum fruits and their main bioactive
      compounds were evaluated upon Aspergillus parasiticus. The GC-EIMS analysis
      showed capsaicin (50.49%) and piperine (95.94%) as the major constituents in C.
      chinense and P. nigrum, respectively. MIC50 values revealed that capsaicin (39
      MUg/mL) and piperine (67 MUg/mL) were lower than those from fruit extracts of C.
      chinense (381 MUg/mL) and P. nigrum (68 MUg/mL). Extracts and bioactive compounds
      showed anti-aflatoxigenic activity. Maximum aflatoxin inhibition occurred at 150
      ug/mL of extracts and compounds. The present study showed satisfactory results
      concerning the effects of ethanolic extract of C. chinense and P. nigrum fruits
      upon A. parasiticus, showing the capabilities of inhibiting fungal growth
      development and altering aflatoxins production.

PMID- 30295074
TI  - Treatment of chronic and extreme ocular hypotension following glaucoma surgery
      with intraocular platelet-rich plasma: A case report.
AB  - PURPOSE: To report a new approach for the treatment of severe ocular hypotony
      secondary to glaucoma filtering surgery with mitomycin C by injecting autologous
      eye platelet-rich plasma (E-PRP) in the anterior chamber to block excessive
      diffuse filtration through an abnormally thinned sclera. METHODS: A 49-year-old
      patient with the Axenfeld-Rieger syndrome and severe chronic hypotony and corneal
      edema following filtering glaucoma surgery with mitomycin C received an isolated
      injection of 0.3 mL of autologous platelet-rich plasma in the anterior chamber.
      RESULTS: Intraocular pressure measured by Goldman's applanation tonometry 6 h
      after the procedure improved to 18 mmHg. Intraocular pressure remained stable
      along the full follow-up period of 6 month. No filtration or hypotony or any
      other complications were observed. CONCLUSION: Intracameral platelet-rich plasma
      (E-PRP) injection was an effective, rapidly effective, and safe procedure for
      treatment of severe chronic ocular hypotony following glaucoma filtrating
      surgery.

PMID- 30295075
TI  - Progress of co-culture systems in cartilage regeneration.
AB  - INTRODUCTION: Cartilage tissue engineering has rapidly developed in recent
      decades, exhibiting promising potential to regenerate and repair cartilage.
      However, the origin of a large amount of a suitable seed cell source is the major
      bottleneck for the further clinical application of cartilage tissue engineering.
      The use of a monoculture of passaged chondrocytes or mesenchymal stem cells
      results in undesired outcomes, such as fibrocartilage formation and hypertrophy.
      In the last two decades, co-cultures of chondrocytes and a variety of mesenchymal
      stem cells have been intensively investigated in vitro and in vivo, shedding
      light on the perspective of co-culture in cartilage tissue engineering. Areas
      covered: We summarize the recent literature on the application of heterologous
      cell co-culture systems in cartilage tissue engineering and compare the
      differences between direct and indirect co-culture systems as well as discuss the
      underlying mechanisms. Expert opinion: Co-culture system is proven to address
      many issues encountered by monocultures in cartilage tissue engineering,
      including reducing the number of chondrocytes needed and alleviating the
      dedifferentiation of chondrocytes. With the further development and knowledge of
      biomaterials, cartilage tissue engineering that combines the co-culture system
      and advanced biomaterials is expected to solve the difficult problem regarding
      the regeneration of functional cartilage.

PMID- 30295076
TI  - Management of diabetic macular edema patients in clinical practice in Spain.
AB  - PURPOSE: Diabetic macular edema is the main cause of blindness in diabetic
      patients. Vascular endothelial growth factor is involved in diabetic macular
      edema pathogenesis. Vascular endothelial growth factor inhibitors are an
      important option in diabetic macular edema therapy. This survey investigates
      actual clinical practice in diabetic macular edema in Spain. METHODS: An expert
      advisory panel of 17 Spanish ophthalmologists developed a 30-item anonymous
      questionnaire about diagnosis, treatment, and follow-up in diabetic macular
      edema. A total of 137 ophthalmologists from 10 Spanish regions completed the
      questionnaire online. RESULTS: Almost all of the respondents (99.3%) record the
      measured visual acuity and perform biomicroscopic anterior (94.9%) and posterior
      (91.2%) segment examinations. Similarly, 100% of responding ophthalmologists
      always/almost always or frequently perform optical coherence tomography. Most
      respondents (65%) always/almost always or frequently perform a retinography. More
      than 50% rarely perform fluorescein angiography. Nearly, all (96.4%) of the
      specialists responded that, in center-involved diabetic macular edema, the first
      treatment is an anti-vascular endothelial growth factor drug. For
      corticosteroids, the first choice of most respondents (91.2%) was the
      dexamethasone implant. In the follow-up, almost all (96.4%) specialists record
      the measured visual acuity and most also perform biomicroscopic anterior (82.5%)
      and posterior (83.2%) segment examination. CONCLUSION: This survey shows the
      actual clinical practice in diabetic macular edema in Spain, finding that anti
      vascular endothelial growth factor therapy is frequently used, and that
      diagnosis, treatments, and follow-up examinations used by specialists are
      homogeneous and according to diabetic macular edema guidelines.

PMID- 30295077
TI  - Does anti-Mullerian hormone predict change in menopausal symptoms following risk
      reducing salpingo-oophorectomy? A prospective observational study.
AB  - OBJECTIVES: The aim of this study was to investigate whether serum anti-Mullerian
      hormone (AMH) predicts symptom burden after risk-reducing salpingo-oophorectomy
      (RRSO) in order to individualize counseling. METHODS: Patient-reported menopausal
      symptoms, sexual functioning, and psychological distress (depression and anxiety)
      were assessed 1 day before (T0) and 6 weeks (T1) and 7 months (T2) after RRSO.
      AMH was assessed before RRSO. Multivariable regression analysis was used to
      investigate the association between AMH and short-term and long-term change in
      symptom burden following RRSO. RESULTS: Ninety-one premenopausal women at high
      risk of ovarian cancer were included. Presurgical AMH was not related
      significantly to change in symptoms post RRSO. As a secondary outcome we found
      that regular menses before RRSO was associated specifically with long-term
      increase in hot flushes (sr = 0.40, p = 0.001; total R2 = 0.171) and depression
      (sr = 0.29, p = 0.012; total R2 = 0.132). Earlier receipt of chemotherapy was
      associated with long-term improvement in sexual functioning (sr = 0.24, p =
      0.041; total R2 = 0.348). CONCLUSION: In this cohort, AMH was not a significant
      predictor of change in symptoms following RRSO. Regular menses prior to RRSO and
      earlier receipt of chemotherapy were significantly, but relatively weakly,
      associated with changes in outcomes 6 weeks and/or 7 months after RRSO.

PMID- 30295078
TI  - From enjoyment to physical activity or from physical activity to enjoyment?
      Longitudinal associations in parent-child dyads.
AB  - BACKGROUND: This longitudinal dyadic study used cross-lagged analyses to examine
      reciprocal patterns of associations between physical activity (PA) enjoyment and
      moderate-to-vigorous PA (MVPA) among children and their parents. METHODS: At Time
      1 (T1) 879 parent-child dyads provided their data. The follow-up (Time 2, T2)
      took place 7-8-months later. MVPA and PA enjoyment scales were filled out
      separately by parents and children at T1 and T2. FINDINGS: Child PA enjoyment
      (T1) predicted a higher level of child MVPA (T2), parental PA enjoyment (T1)
      explained a higher level of parental MVPA (T2), and parental MVPA (T1) predicted
      a higher level of parental PA enjoyment (T2). Furthermore, child PA enjoyment
      (T1) predicted a higher level of parental PA enjoyment (T2). CONCLUSIONS: Child
      PA enjoyment was the key variable predicting child and parental outcomes. In
      particular, it explained child MVPA, but also PA enjoyment among parents.

PMID- 30295080
TI  - An unusual case of acoria in Sturge-Weber syndrome.
AB  - We present an unusual case of Sturge-Weber syndrome whose main clinical
      manifestations were nevus flammeus, seizures, glaucoma, and acoria. To our
      knowledge, the combination of Sturge-Weber syndrome and acoria has not been
      previously reported.

PMID- 30295081
TI  - Perceiving college peers' alcohol consumption: temporal patterns and individual
      differences in overestimation.
AB  - OBJECTIVE: This study examines temporal patterns and individual differences of
      overestimation in alcohol norm perception within a social network. DESIGN:
      Hundred psychology freshmen indicated biweekly during their first semester the
      drinks they consumed, the perceived average of their peers' consumption, and with
      whom they were acquainted. At baseline, trait self-control was assessed. MAIN
      OUTCOME: The moderation of alcohol consumption overestimation by time and
      individual characteristics was explored. RESULTS: Results show that students
      overestimated alcohol consumption of their acquainted peers by 1.22 drinks (p <
      .001). For time periods at which peers reported high consumption, overestimation
      decreased. Additionally, individuals reporting high alcohol consumption (b = 
      0.25, p < .001) and low self-control (b = 0.27, p = .010) showed higher
      overestimation. CONCLUSIONS: Students overestimate the alcohol consumption of
      peers not fully accounting for changes in peer-reports. Furthermore, individual
      differences suggest informational and motivational processes underlying
      overestimation.

PMID- 30295079
TI  - Prevention of Bortezomib-Related Peripheral Neuropathy With Docosahexaenoic Acid
      and alpha-Lipoic Acid in Patients With Multiple Myeloma: Preliminary Data.
AB  - BACKGROUND AND AIMS: Peripheral neuropathy is a common complication of
      chemotherapy that can induce marked disability that negatively affects the
      quality of life in patients with multiple myeloma (MM). The aim of this study was
      to prevent the onset or the worsening of peripheral neuropathy in MM patients
      treated with bortezomib (BTZ), using a new nutritional neuroprotective compound.
      We report preliminary results of 18 out of 33 patients who completed the study.
      METHODS: We administered a tablet of Neuronorm to patients, containing
      docosahexaenoic acid 400 mg, alpha-lipoic acid 600 mg, vitamin C 60 mg, and
      vitamin E 10 mg bid for the whole follow-up period. Neurological visit
      assessment, electroneurography, and evaluation scales were performed at baseline
      and after 6 months. RESULTS: At 6 months, 8 patients had no chemotherapy-induced
      peripheral neuropathy, while 10 patients experienced chemotherapy-induced
      peripheral neuropathy of grade 1 according to the Common Terminology Criteria for
      Adverse Events, one of them with pain. Seventeen patients did not report painful
      symptoms; no limitation of functional autonomy and stability in quality of life
      domains explored was observed. CONCLUSIONS: Our results seem to indicate that
      early introduction of a neuroprotective agent in our patients with MM treated
      with BTZ could prevent the onset or the worsening of neuropathic pain, avoiding
      the interruption of the therapy with BTZ, and maintaining a good functional
      autonomy to allow normal daily activities. Despite the limitations due to the
      fact that this is a preliminary study, in a small population, with short follow
      up, our data seem to indicate that the nutraceutical may have some potential to
      be considered for a future trial.

PMID- 30295082
TI  - Author's reply.

PMID- 30295083
TI  - SAR342434 - an insulin biosimilar for the treatment of type II diabetes.
AB  - INTRODUCTION: The global incidence of diabetes mellitus is increasing, with a
      concomitant rise in individual and overall treatment costs. The development of
      biosimilars contributes to the facilitation of greater access to treatment.
      SAR342434 is a biosimilar follow-on of insulin lispro, a key therapeutic for the
      treatment of diabetes mellitus, and it is currently under phase III clinical
      trials. Areas covered: In this review we discuss the recent updates on clinical
      data obtained from phase III trials to compare the equivalence and similarity of
      SAR342434 to insulin lispro, including pharmacokinetics (PKs), pharmacodynamics,
      clinical efficacy, safety and immunogenicity. Expert opinion: The rising
      treatment costs of diabetes mellitus poses a challenge to public health
      enterprises worldwide. The development of biosimilars is probably a good choice
      to solve this conundrum. Based on the available clinical trials, it is confirmed
      that SAR342434 is equivalent to the reference insulin lispro, with similar
      pharmacodynamics, PKs, anti-hyperglycemic efficacy and safety. These attributes
      show the good potential of SAR342434 for serving as an alternative to achieve the
      glycemic control in patients with diabetes mellitus.

PMID- 30295084
TI  - Surgical Technique and Anatomical Considerations for the Modified L'Episcopo
      Tendon Transfer.
AB  - BACKGROUND: Birth brachial plexus injury usually affects the upper trunks of the
      brachial plexus and can cause substantial loss of active shoulder external
      rotation and abduction. Due to the unbalanced rotational forces acting at the
      glenohumeral joint, the natural history of the condition involves progressive
      glenohumeral joint dysplasia with associated upper limb dysfunction. Surgical
      reconstruction methods have been described previously by Sever and L'Episcopo,
      and modified by Hoffer and Roper to release the adduction contracture and to
      restore external rotation and shoulder abduction. METHODS: The authors describe
      their preferred technique for contracture release and tendon transfer to improve
      external rotation and shoulder abduction. Pertinent anatomy and highlights of
      surgical exposure are reviewed. RESULTS: The senior author has utilized this
      technique with consistent clinical outcomes to improve shoulder function for
      patients with persisting nerve palsy associated with birth brachial plexus
      injury. A review of the literature supports utilization of this technique.
      CONCLUSIONS: Transfer of the latissimus dorsi and teres major to the posterior
      rotator cuff for reanimation of shoulder abduction and external rotation deficits
      associated with birth brachial plexus injury is a safe and reliable technique.
      Careful patient selection and attention to surgical detail are critical for
      optimal outcomes.

PMID- 30295085
TI  - Type D personality and social relations in adults with diabetes: results from
      diabetes MILES - The Netherlands.
AB  - OBJECTIVE: To examine whether individual differences in Type D personality
      (combination of negative affectivity (NA) and social inhibition (SI)) could
      explain heterogeneity in perceived social support and relationship adjustment
      (intimate partner relationship) among people living with diabetes. DESIGN: In the
      Diabetes MILES-The Netherlands survey, 621 adults with type 1 or type 2 diabetes
      (54% female, age: 56 +/- 14 years) completed measures of Type D personality
      (DS14), perceived social support and relationship adjustment. We used established
      DS14 cut-off scores to indicate Type D personality, high NA only, high SI only
      and reference groups. RESULTS: Participants from the Type D and NA only groups
      perceived lower levels of social support (Welch[3,259] = 37.27, p < 0.001), and
      relationship adjustment (Welch[3,191] = 14.74; p < 0.01) than those from the SI
      only and reference groups. Type D was associated with lower social support
      (lowest quartile; adjusted OR = 8.73; 95%CI = 5.05 ~ 15.09; p < 0.001) and lower
      relationship adjustment (lowest quartile; adjusted OR = 3.70; 95%CI = 2.10 ~
      6.53; p < 0.001). Type D was also associated with increased levels of loneliness.
      CONCLUSION: Participants with Type D and participants with high NA only tend to
      experience less social support and less relationship adjustment. Type D
      personality was also associated with more loneliness. Experiencing lower social
      support and relationship adjustment may complicate coping and self-management in
      people with diabetes.

PMID- 30295086
TI  - Hybrid nanocarrier system for guiding and augmenting simvastatin cytotoxic
      activity against prostate cancer.
AB  - Prostate cancer is the most common non-skin cancer among men. Though statins are
      mainly used as antihyperlipidemic drugs, many studies have reported their
      proapoptotic and antimetastatic activities on prostate cancer. However, the poor
      solubility and insufficient delivery of statins in tumor site limit their
      anticancer activity. The present study introduces an efficient hybrid drug
      delivery system for the treatment of prostate cancer. The system involves the
      chemical conjugation of Simvastatin (SMV), a statin compound, to acid-terminated
      poly(D, L-lactic-co-glycolic acid), PLGA chains followed by its conversion into
      nanoparticles (NPs), with in situ physical incorporation of more SMV and
      superparamagnetic iron oxide nanoparticles (SPIONS) into the PLGA NPs. The PLGA
      based hybrid nanocarrier system has been designed in such a way to evade the low
      bioavailability of SMV, confer sustained release of both encapsulated and
      chemically conjugated SMV, as well as enhancing the anti-cancer effect of the
      formula via the magnetic targeting with the aid of the encapsulated SPIONS.
      Magnetism, morphological and physicochemical characterizations, as well as in
      vitro release studies were performed. Besides, cytotoxicity on human prostate
      cancer cell line (PC-3) was evaluated using MTT assay, cell cycle arrest
      analysis, annexin V/propidium iodide apoptosis assay and ELISA immunoassay for
      apoptotic enzyme. Optimum PLGA-based hybrid nanocarrier significantly improved
      the SMV anticancer activity against human prostate cancer cell line through both
      apoptosis mechanism and retardation of G2-M phase of cell cycle. Also, the up
      regulation of the Caspase 3 was aligned with cytotoxicity study's findings.

PMID- 30295087
TI  - Adverse childhood experiences as a predictor of attendance at a health-promotion
      program.
AB  - This short-term longitudinal study examined whether adverse childhood experiences
      predicted attendance at a fitness program. We asked undergraduates participating
      in a group fitness program at a university to complete measures of mental health
      and adverse childhood experiences at the start of the semester. Attendance data
      were obtained from the recreational center at the end of the semester. Adverse
      childhood experiences predicted attendance after parental education and mental
      health were taken into account. To our knowledge, this is the first study to
      demonstrate that more adverse childhood experiences predict lower attendance at a
      health-promotion program. Findings suggest a need for adverse childhood
      experiences screening to prevent drop-out.

PMID- 30295088
TI  - Adding insult to injury: Perceived inequity modulates pain perception.
AB  - Inequity and pain typically co-appear during disasters or illnesses and have
      significant effects on health. However, the relationship between inequity and
      pain perception is poorly understood. Four studies investigated whether perceived
      inequity modulates pain perception using different priming paradigms and pain
      measurements. Studies 1-3 consistently revealed that participants perceived pain
      more intensely and rapidly after inequity priming. Study 4 demonstrated that
      inequity in cancer patients predicts pain perception after controlling for
      individual differences in equity sensitivity and pain sensitivity. The findings
      suggest that equity may help manage adversity in achieving mental and physical
      health.

PMID- 30295089
TI  - A series of n-of-1 studies examining the interrelationships between social
      cognitive theory constructs and physical activity behaviour within individuals.
AB  - OBJECTIVES: Research supports the ability of social cognitive theory (SCT) to
      explain physical activity (PA) behaviour, but most studies have examined this
      theory between individuals in large group studies. The aim of the present study
      was to examine the interrelationships between SCT constructs and PA within
      individuals of varying activity levels. DESIGN: Correlational n-of-1 studies.
      METHODS: Six adults aged 29-65 with varying levels of PA provided daily measures
      of PA, and completed probe measures over a four-week period of SCT constructs
      (e.g. barrier self-efficacy, goal setting, planning, social support, outcome
      expectations, perceived barriers, enjoyment). Data were analysed using cross
      correlational time series analysis. RESULTS: Cross-correlation analysis showed
      that at least one SCT construct was associated with PA in five participants,
      although no individual had the same pattern of associations across the study. On
      some occasions, SCT constructs predicted subsequent PA, but at other times, PA
      engagement caused a subsequent change in the SCT construct. There were also
      examples of PA and SCT constructs being concurrently associated. CONCLUSIONS: SCT
      factors are associated with variations in PA behaviour, but the cause and effect
      of these relationships within individuals is complex.

PMID- 30295090
TI  - Biodegradable Microsphere-Hydrogel Ocular Drug Delivery System for Controlled and
      Extended Release of Bioactive Aflibercept In Vitro.
AB  - PURPOSE: Current standard of care for neovascular eye diseases require repeated
      intravitreal bolus injections of anti-vascular endothelial growth factors (anti
      VEGFs). The purpose of this study was to validate a degradable microsphere
      thermoresponsive hydrogel drug delivery system (DDS) capable of releasing
      bioactive aflibercept in a controlled and extended manner for 6 months. MATERIALS
      AND METHODS: The DDS was fabricated by suspending aflibercept-loaded poly(lactic
      co-glycolic acid) microspheres within a biodegradable poly(ethylene glycol)-co-(l
      lactic acid) diacrylate/N-isopropylacrylamide (PEG-PLLA-DA/NIPAAm)
      thermoresponsive hydrogel. Encapsulation efficiency of DDSs and in vitro release
      profiles were characterized by iodine-125 radiolabeled aflibercept. The
      degradation of hydrogel was determined by dry weight changes. The cytotoxicity
      from degraded DDS byproducts was investigated by quantifying cell viability using
      LIVE/DEAD(r) assay. In addition, dot blot and enzyme-linked immunosorbent assay
      were used to determine the bioactivity of released drug. Finally, morphology of
      microspheres and hydrogel were investigated by cryo-scanning electron microscopy
      before and after thermal transformation. RESULTS: The microsphere-hydrogel DDS
      was capable of releasing bioactive aflibercept in a controlled and extended
      manner for 6 months. The amount and rate of aflibercept release can be controlled
      by both the cross-linker concentration and microspheres load amount. The initial
      burst (release within 24 h) was from 37.35 +/- 4.92 to 74.56 +/- 6.16 ug (2 and 3
      mM hydrogel, each loaded with 10 and 20 mg/ml of microspheres, respectively),
      followed by controlled drug release of 0.07-0.15 ug/day. Higher PEG-PLLA-DA
      concentration (3 mM) degraded faster than the lower concentration (2 mM). No
      significant cytotoxicity from degraded DDS byproducts was found for all
      investigated time points. Bioactivity of released drug was maintained at
      therapeutic level over entire release period. CONCLUSIONS: The microsphere
      hydrogel DDS is safe and can deliver bioactive aflibercept in a controlled
      manner. This may provide a significant advantage over current bolus injection
      therapies in the treatment of ocular neovascularization.

PMID- 30295091
TI  - Gynecological-endocrinological aspects in women carriers of BRCA1/2 gene
      mutations.
AB  - Women carriers of mutations in the genes BRCA1 and BRCA2 coding for tumor
      suppressor proteins are at high risk of developing breast and ovarian cancers.
      Hereditary breast and ovarian cancers due to BRCA pathogenic mutations occur at
      earlier ages: mean age 43 years at diagnosis of breast cancer for BRCA1
      mutations; onset of ovarian cancer up to 10-21% by age 50 years. Preventive
      strategies are then defined in the reproductive years. The National Comprehensive
      Cancer Network (NCCN) guidelines define that BRCA1/2 genetic testing should begin
      with the affected cancer individual (BRCA1/2 full sequencing); then, family
      members should be tested for the specific gene mutation found. A woman known to
      be a carrier needs a strict specific surveillance strategy to achieve early
      diagnosis. The NCCN proposes breast imageneological surveillance beginning at age
      25 years; ovarian surveillance beginning at age 30-35 years. Concomitantly, risk
      reducing strategies should be analyzed: surgical or pharmacological. When
      prophylactic bilateral salpingo-oophorectomy is performed before menopause,
      estrogen replacement therapy could be required. For BRCA, we review the risks of
      cancer in mutations carriers, criteria for genetic testing, surveillance and risk
      reduction strategies, and the safety of prescribing hormone therapy when needed.

PMID- 30295092
TI  - Science and Terminology in-between Empires: Ukrainian Science in a Search for its
      Language in the nineteenth century.
AB  - Ukrainian science and its terminology in the nineteenth century experienced a
      number of twists and turns. Divided between two empires, it lacked institutions,
      scholars pursuing it, and a unified literary language. One could even say that
      until the late nineteenth century there was a possibility for two communities
      with two literary languages to emerge - Ruthenian (Habsburg Empire) and Ukrainian
      (Russian Empire). Eventually, both communities and languages merged. This article
      tracks the meanderings of this process, arguing that scholarly publications
      played a crucial role in shaping the standard for the scientific language. The
      article follows the biography of the naturalist Ivan Verhrats'kyi (1846-1919),
      the author of the first dictionaries of naturalist terminology in Ruthenian in
      1860, a translator and author of textbooks, and the head of the Mathematical
      Naturalist-Medical Section of the Shevchenko Society in L'viv. He thus shaped
      many Ruthenian, and then Ruthenian-Ukrainian scholarly projects. Initially
      successful with his approach to making the Ruthenian scientific language
      vernacular, in the 1890s his approach was losing ground to the
      internationalization of vocabulary and to the growing pressure toward the
      unification of Ruthenian and Ukrainian. Finally, in the beginning of the
      twentieth century, Verhrats'kyi became marginalized within the Ukrainian
      scholarly community. By discussing the history of a minority language within
      imperial structures, I argue that the media in which scholarly work was published
      requires special attention. In the Ruthenin-Ukrainian case, they determined the
      standard for scientific language. Lacking professional journals, Ruthenian
      scholars published in the 1860s-late 1880s in popular newspapers and in school
      textbooks, requiring them to use a language that was near to the spoken tongue of
      the Habsburg province. Once the political situation changed, favoring Ruthenian
      Ukrainian unification, and scholarly journals appeared and transgressed the
      imperial boundary, the favored language had to be transimperial, ousting out the
      vernacular.

PMID- 30295093
TI  - Concerns about the review of vaginal progesterone and the vaginal first-pass
      effect.

PMID- 30295094
TI  - Adjuvant therapy for high-risk endometrial cancer: recent evidence and future
      directions.
AB  - INTRODUCTION: Although the majority of women with endometrial cancer have a
      favorable prognosis due to early symptoms, 15-20% have high-risk disease features
      and are at increased risk of recurrence. In order to improve prognosis for these
      patients, several trials have compared chemotherapy (CT), radiotherapy (RT) or
      the combination of CTRT. Areas covered: This review focuses on the current
      evidence on adjuvant treatment for women with high-risk endometrial cancer and
      future perspectives. Expert commentary: For stage I-II high-risk endometrial
      cancer, external beam radiotherapy ensured good local control and no significant
      benefit in progression-free or overall survival was found with the addition of
      chemotherapy in 2 recent randomized trials. For women with stage III disease, the
      combination of chemotherapy and radiotherapy improved progression-free survival
      with a non-significant improvement of overall survival. Adjuvant chemotherapy
      alone resulted in higher rates of pelvic and para-aortic recurrence. More
      toxicity and reduced quality of life were found during and after adjuvant CTRT.
      It is essential to discuss the benefits and disadvantages of chemotherapy and
      radiotherapy with individual patients for shared decision-making. Translational
      research is ongoing to further characterize individual tumors, identify
      sensitivity to (immuno)therapies and find new treatment targets to improve
      outcomes.

PMID- 30295095
TI  - Pathogenesis of adult onset still's disease: current understanding and new
      insights.
AB  - INTRODUCTION: Adult-onset Still's disease (AOSD) is a rare inflammatory disorder
      typically characterized by fever, arthritis, and hyperferritinemia. Concerning
      AOSD pathogenesis, it is categorized as a multigenic autoinflammatory disease, at
      the 'crossroads' of autoinflammatory and autoimmune diseases, because of the
      involvement of both arms of immune system. Areas covered: This work is conceived
      as narrative overview assessing the pathogenesis of AOSD. We performed a
      narrative synthesis of published information, summarizing the contents of
      previous studies and providing a possible rationale for future researches.
      MedLine database was searched for identification of suitable studies. In
      reporting the available evidence, we described the results according to distinct
      pathogenic steps associated with different clinical features of the disease.
      Expert commentary: AOSD is a systemic severe inflammatory disorder of unknown
      etiology affecting young adults. Although pathogenesis of the disease is not
      fully clarified, the role of the pro-inflammatory cytokines is well-recognized
      and biologic drugs, blocking these molecules, are routinely used in clinical
      practice. Finally, given that multiple recent lines of evidence have suggested
      new insights in AOSD pathogenesis, new therapeutic targets have been highlighted
      and the results of studies with new drugs could further improve the management of
      these patients.

PMID- 30295096
TI  - Relationship between P-wave duration and the risk of atrial fibrillation.
AB  - INTRODUCTION: P-wave duration (PWD) is an electrocardiographic (ECG) marker
      reflecting atrial conduction, and studies have shown that its prolongation is
      associated with atrial fibrillation. Areas covered: This review addresses the
      relationship between PWD and atrial fibrillation, how anatomic and physiologic
      changes in the atria potentiate the risk for atrial fibrillation, and how these
      atrial anatomic and physiologic changes relate to PWD. Other P-wave related
      entities, such as P-wave terminal force in V1, PR interval, and P wave axis are
      also addressed. Expert commentary: Atrial fibrillation is a manifestation of the
      underlying atrial disease. Fibrotic collagen deposition interrupts the electrical
      flow and thus can potentiate the transition from sinus rhythm to atrial
      fibrillation. PWD is an ECG parameter that provides insight into the intricacies
      of the atria and could be a useful marker for assessing the risk for atrial
      fibrillation. The main obstacle for broad utilization of PWD is that it is not
      routinely reported on the printout of the electrocardiogram.

PMID- 30295097
TI  - Combination treatment of advanced pancreatic cancer using novel vaccine and
      traditional therapies.
AB  - INTRODUCTION: Pancreatic cancer is a highly malignant disease with high treatment
      resistance. Many patients are diagnosed in a very advanced state, and few
      patients can be curatively resected. With FOLFIRINOX and nab-paclitaxel plus
      gemcitabine, the prognosis of advanced pancreatic cancer has improved, yet many
      patients cannot survive longer than a year. Therefore, new therapeutic approaches
      are needed. Cancer vaccine therapy is characterized by controlling cancer by a
      cancer-specific immune reaction with few adverse events. Thus, a cancer peptide
      vaccine is considered promising for pancreatic cancer patients, who are often in
      poor general condition at diagnosis. Areas covered: This article reviews
      available data from recent clinical trials of the novel cancer vaccine therapy in
      combination with traditional chemotherapy or radiotherapy for pancreatic cancer,
      and the prospect will be described. Expert commentary: In clinical trials of the
      novel cancer vaccine therapy in combination with traditional therapy, many
      studies have failed to outperform traditional therapy, although some effects were
      recognized in subgroups. What is necessary in the future for cancer vaccine
      therapy to improve the prognosis of pancreatic cancer is combination of immune
      checkpoint blockade to release immune escape mechanism and combination with
      strong multi-drug combination chemotherapy.

PMID- 30295098
TI  - Embracing the polypill as a cardiovascular therapeutic: is this the best
      strategy?
AB  - INTRODUCTION: Cardiovascular disease (CVD) is an important cause of mortality and
      morbidity worldwide. CVD morbidity and mortality are associated with significant
      financial costs related to hospitalization, medication, and lost productivity.
      The concept of the 'polypill' for the reduction of cardiovascular risk was
      proposed in 2000. A polypill is a fixed combination of drugs in a single tablet
      or capsule. The initial polypill consisted of three different classes of
      antihypertensive drugs (each at half dose), in addition to aspirin, a statin, and
      folic acid. The challenge today is to produce polypills containing drugs with
      established efficacy and complementary actions. Areas covered: The authors
      provide their expert perspectives on the polypill and consider the randomized
      clinical trials that have evaluated the safety, efficacy, adherence, and cost
      effectiveness of polypills. Expert opinion: The polypill makes prescribing easier
      by reducing the need for complex treatment algorithms and dose titration. It also
      appears to be cost-effective. However, there are several issues that need to be
      addressed before the polypill can be used routinely. A single polypill
      formulation may not be suitable for all patients. It may be necessary to develop
      several types of polypill to meet the needs of different patient groups.

PMID- 30295099
TI  - Administrative ethics: Good intentions, bad decisions.
AB  - The Canadian healthcare system is costly. Each day, health leaders must make
      decisions about what healthcare services will be offered, how they will be
      funded, to whom they will be made available, and within what administrative and
      clinical structure they will be managed and delivered. These decisions, their
      justification, and the ethics framework employed can vary greatly across the
      Canadian landscape. These high-stakes decisions must not only draw upon
      healthcare science but the science of business finance, risk management, and
      organizational design. However, in equal measure and often overlooked, these
      decisions must draw upon our values, upon our ethics. Sometimes we get it right,
      and other times, decidedly less so. When timely and fair access to effective and
      efficient healthcare services is not rendered, matters of justice, fairness,
      rights, and a host of other constructs are often cited. However, these important
      constructs are commonly misunderstood, contributing, in part, to well-intentioned
      but ultimately unethical decisions.

PMID- 30295100
TI  - Ethical leadership and why health information management professionals need to be
      involved. Commentary on Health information is central to changes in healthcare: a
      clinician's view (Hoyle, 2018).
AB  - Philip Hoyle presents a compelling argument for the significant and highly valued
      role that the management of health information plays in the Australian healthcare
      system and the delivery of health services in this country. However, he also
      brings to our attention the ill-defined nature of the ethical oversight of this
      very information. Hoyle uses words such as "honesty," "commitment to
      beneficence," "commitment to equity" and "respect for variation" when describing
      the characteristics of ethical leadership. He singles out health information
      management professionals - Health Information Managers (HIMs) and Clinical Coders
      (CCs) - as the key professional group who need to step up and seize the
      initiative, get conversations going, form partnerships, do research and publish
      findings, so the knowledge and insights that the health information management
      profession has the potential to offer are not only more widely known and
      understood but also more useful to others working in the healthcare arena. Hoyle
      calls on health information management professionals to step out from behind the
      scenes and take responsibility for the ethical use of the information they help
      produce. Hoyle's words resonated powerfully with me, particularly with respect to
      the clinical coding workforce in Australia, which is made up of trained CCs and
      qualified HIMs. In a truly ethical environment, HIMs and CCs would not be asked
      to meet performance indicators for increased funding metrics or to change codes
      to avoid triggering certain indicators; they would simply be asked to ensure
      complete, accurate coding for every episode of care. This is what ethical
      leadership would look like. I am concerned about our clinical coding workforce. I
      am now asking, are our CCs and HIMs up to the task of taking back absolute and
      unchallenged ownership of their particular skill set, which makes them the
      keepers of the clinical coding standards and the experts in accurate and complete
      code assignment?

PMID- 30295101
TI  - Epicutaneous immunotherapy: the next step for food allergy desensitization.

PMID- 30295102
TI  - Introduction to the Special Issue on Cognitive and Behavioral Flexibility in Fear
      and Anxiety Disorders.
AB  - Converging lines of research highlight the significance of cognitive and
      behavioral flexibility in the etiology, maintenance, and treatment of fear and
      anxiety disorders. We have developed a Special Issue to highlight recent
      empirical investigations, contemporary theory, and novel directions for future
      study. It is hoped that this special issue will (a) underscore the centrality of
      cognitive and behavioral flexibility to fear- and anxiety-related
      psychopathology, (b) call attention to cognitive science approaches investigating
      related neuropsychological correlates, and (c) highlight novel experimental and
      theoretical research on germane contextual factors.

PMID- 30295103
TI  - Nephroprotective Effect of Cilostazol And Verapamil Against Thioacetamide-Induced
      Toxicity in Rats may Involve Nrf2/HO-1/NQO-1 Signaling Pathway.
AB  - Cilostazol and verapamil are widely used cardiovascular drugs, explored a
      beneficial effect on different organs-induced toxicities. We investigated whether
      the Nrf2 (nuclear erythroid factor 2) and its downstream pathway may be involved
      in the protective role of these drugs against TAA-induced renal damage. Renal
      biomarkers (creatinine and urea) and histopathology were observed. Antioxidant
      and oxidant indicators; superoxide dismutase (SOD), reduced glutathione (GSH),
      malondialdehyde (MDA), and total nitrite (NO) were also measured. Antioxidant
      markers like; Nrf2/hemoxegenase-1 (HO-1) and NADPH quinone oxidoreductase -1 (NQO
      1) expressions were determined by ELISA and immunohistochemistry. Cilostazol and
      verapamil pre-treatment improved serum creatinine and urea elevation. Examined
      drugs have also an ameliorative effect on TAA-induced elevation in MDA and NO
      activities and antioxidant enzymes; SOD and GSH. Additionally, the pre-treated
      drugs significantly up-regulated Nrf2/HO-1/NQO-1 expression levels. In
      conclusion, cilostazol and verapamil exerted their protective effects partially
      via a Nrf2/HO-1/NQO-1 activation pathway with anti-oxidant roles.

PMID- 30295104
TI  - Reply to "Contemporary Management of the High-Risk Pulmonary Embolism: The Clot
      Thickens".

PMID- 30295105
TI  - Proton pump inhibitors: use and misuse in the clinical setting.
AB  - INTRODUCTION: The introduction of proton pump inhibitors (PPIs) into clinical
      practice has greatly improved our therapeutic approach to acid-related diseases
      for their efficacy and safety. Areas Covered: The following evidence-based
      indications for PPI use are acknowledged by many scientific societies: treatment
      of the various forms and complications of gastroesophageal reflux disease,
      eradication of H. pylori infection in combination with two or more antibiotics,
      short- and long-term therapy of H. pylori-negative peptic ulcers, healing, and
      prevention of NSAID/COXIB-associated gastric ulcers, co-therapy with endoscopic
      procedures to control upper digestive bleeding and medical treatment of Zollinger
      Ellison syndrome. Expert Commentary: Despite the above well-defined indications,
      however, the use of PPIs continues to grow every year in both western and eastern
      countries and the endless expansion of the PPI market has created important
      problems for many regulatory authorities for two relevant features: the
      progressive increase of the costs of therapy and the greater potential harms for
      the patients. The major reasons for the misuse of PPIs are the prevention of
      gastro-duodenal ulcers in patients without risk factors and the stress ulcer
      prophylaxis in non-intensive care units, steroid therapy alone, anti-platelet or
      anti-coagulant treatment in patients without risk of gastric injury and the
      overtreatment of functional dyspepsia.

PMID- 30295106
TI  - Evaluation of the premature chromosome condensation scoring protocol after proton
      and X-ray irradiation of human peripheral blood lymphocytes at high doses range.
AB  - PURPOSE OF THE STUDY: One of the main difficulties in radiation dose assessment
      is cells inability to reach mitosis after exposure to acute radiation. Premature
      chromosome condensation (PCC) has become an important method used in biological
      dosimetry in case of exposure to high doses. Various ways to induce PCC including
      mitotic cells fusion, chemical stimulation with calyculin A or okadaic acid give
      wide spectrum of application. The main goal of this study was to evaluate the
      utility of drug-induced PCC scoring procedure by testing 2 experimental modes
      where 150 and 75 G2/M-PCC phase cells were analyzed after exposure to high dose
      proton and X-ray radiation. Another aim is to determine the differences in
      cellular response induced by proton and photon radiation using a HPBL in vitro
      model as a further extension of our previous studies involving doses up to 4.0
      Gy. MATERIALS AND METHODS: Total body exposure was simulated by irradiating whole
      blood collected from a healthy donor. Whole blood samples were exposed to two
      radiation types: 60 MeV protons and 250 kVp X-rays in the dose range of 5.0-20.0
      Gy, the dose rate for protons was 0.075 and 0.15 Gy/s for X-rays. Post 48 h of
      human peripheral blood lymphocytes (HPBL) culture, calyculin A was added. After
      Giemsa staining, chromosome spreads were photographed and manually analyzed by
      scorers in the G2/M-PCC phase. In order to check the consistency of obtained
      results all scorers followed identical scoring criteria. Additionally, PCC index
      kinetics was evaluated for first 500 cells scored. CONCLUSIONS: Here we provide a
      different method of results analysis. Presented dose-response curves were
      obtained by calculating the value of counted excess chromosome fragments. The
      results indicated that obtained dose estimates as adequate in the high dose range
      till 18.0 Gy for both studied radiation types, giving an opportunity to further
      improve PCC assay procedure and shorten the analysis time i.e. in case of partial
      body exposure. Moreover, the study presents preliminary results of HPBL cellular
      response after proton irradiation at high doses range showing differences of PCC
      index kinetics for different cell classes and cell distribution.

PMID- 30295107
TI  - Two Different Buprenorphine Treatment Settings With Similar Retention Rates:
      Implications for Expanding Access to Treatment for Opioid Use Disorder.
AB  - BACKGROUND: There is considerable need for effective and accessible treatment for
      opioid use disorder. AIMS: Our study explored differences in buprenorphine
      treatment retention and duration, with a focus on selected sociodemographic
      factors and treatment indicators, in two different settings: an office-based
      buprenorphine induction and stabilization clinic (OBIC) and a community-based
      primary care clinic (CPC). METHOD: This nonexperimental retrospective chart
      review compared demographic information and buprenorphine treatment details,
      including treatment retention and duration. RESULTS: There were no statistically
      significant differences in buprenorphine treatment indicators between the OBIC
      and CPC groups, with two exceptions: the number of written buprenorphine
      prescriptions was significantly greater for the OBIC group, as was the number of
      filled buprenorphine prescriptions. CONCLUSIONS: Given similar treatment
      retention and duration in two different buprenorphine treatment settings, our
      findings suggest that access to buprenorphine treatment in standard integrated
      care settings can be supplemented by novel treatment structures such as the OBIC
      in order to increase access to care during the current opioid epidemic.

PMID- 30295108
TI  - Sweet care against sugar bitterness, designing health-based electronic game.
AB  - Health-based electronic games present an innovative tool to deal with mental and
      behavioral disorders as well as physical. An appropriately designed game can
      optimize health care. The aim of this study was to establish a design for health
      based electronic games model and to develop a sample game in diabetes. This study
      was carried out in two phases: first, the design of a health-based electronic
      game framework and second, the design and production of sweet care game. There
      were two intended information prerequisites: determination of effective
      components in models of behavior change and validation of these components on
      health topics and structural formation of a game. The game framework design was
      presented. In the second phase, a sample of the game was developed in the field
      of diabetes. Important components to empower people were ranked using the
      Friedman test in the following order: self-learning, treatment, mental
      empowerment, condition management, healthy eating and physical activity. The axis
      of self-learning received the highest rating from the perspective of the subjects
      with an average of 3.93 percent. Another part was the game framework with
      components as follows: application areas, educational content for change
      behavior, resources, game structure and game production. Finally, the sweet care
      game was designed on diabetes with educational, technological and clinical
      content. The health-based electronic game designed on a systematic framework
      could be applied as a tool to expanding the knowledge base on how to create
      effective health-based digital games that entertain while promoting behavior
      change.

PMID- 30295109
TI  - Effect of Magnesium Loading Dose on Insulin Resistance in Patients With Stress
      Induced Hyperglycemia: A Randomized Clinical Trial.

PMID- 30295110
TI  - Maternal levels of growth differentiation factor-15 in patients with
      preeclampsia.
AB  - OBJECTIVE: Growth differentiation factor-15 (GDF-15) is a stress-induced cytokine
      and related to the prognosis of cardiovascular diseases. Our purpose is to
      measure the maternal levels of GDF-15 in patients with early-onset preeclampsia
      (EOPE) and late-onset preeclampsia (LOPE). METHODS: This cross-sectional study
      was conducted including 72 pregnant women, 23 with normal pregnancies and 49 with
      preeclampsia (26 with EOPE and 23 with LOPE). Maternal serum levels of GDF-15
      were measured by using enzyme-linked immunosorbent assay kits. RESULTS: The
      median serum GDF-15 level was found to be the highest in the EOPE group (EOPE:
      441.7 pg/ml). The median serum GDF-15 levels were higher in women with
      preeclampsia than in the control group (309.7 pg/ml vs. 436.6 pg/ml, p: 0.009).
      CONCLUSION: Our findings suggest GDF-15 increased as a response to endothelial
      injury caused by cytokines triggered by preeclampsia.

PMID- 30295111
TI  - Evaluation of a crosswalk between the European Quality of Life Five Dimension
      Five Level and the Menopause-Specific Quality of Life questionnaire.
AB  - OBJECTIVES: Postmenopausal (PM) women taking therapies using estrogens plus
      progestogens (EPTs) can experience side effects (breast pain, vaginal
      spotting/bleeding). Sensitivity of the European Quality of Life Five Dimension
      Five Level (EQ-5D-5L) in measuring quality of life of PM women experiencing side
      effects of EPTs is unknown. A crosswalk between the Menopause-Specific Quality of
      Life (MENQOL) questionnaire and the EQ-5D-5L was assessed. METHODS: The measures
      were administered to 352 PM women (side effects = 202; control = 75; untreated =
      75) in a non-interventional study. MENQOL total scores, treated as continuous and
      categorical predictors, were mapped onto EQ-5D-5L utilities using regression.
      Ordinary least-squares regression using averaged scores over time, goodness of
      fit, and estimated coefficients was also assessed. RESULTS: Mean age was 53.7
      years. The first model (MENQOL as a continuous variable) showed a moderate
      correlation (-0.589) and statistically significant relationship with the EQ-5D-5L
      (p < 0.001), with an equation of EQ-5D-5L = 0.992 - 0.042 * MENQOL. The EQ-5D-5L
      mean scores were comparable (side effects = 0.854; control = 0.927; untreated =
      0.836) to MENQOL mean scores estimated in the first model (side effects = 0.865
      [standard deviation 0.07]; control = 0.909; untreated = 0.833). Linearity
      assumptions were supported with MENQOL scores as a categorical predictor.
      Goodness of fit was moderate (R2 = 0.347; root mean squared error = 0.093).
      CONCLUSION: The crosswalk supports conversion of MENQOL scores to EQ-5D-5L
      derived health utilities for group-level analyses in PM women.

PMID- 30295112
TI  - CD73 expression in tissue granulomas in distinguishing intestinal tuberculosis
      from Crohn's disease in a South African cohort.
AB  - INTRODUCTION: Overlap of clinical, endoscopic and radiographic features, coupled
      with a poor microbiological yield makes differentiating Crohn's disease (CD) from
      intestinal tuberculosis (ITB) challenging. A potential histological
      differentiating mechanism is the use of immunohistochemical staining for the
      mesenchymal stem cell marker CD73, as a pilot study showed ITB but not CD
      granulomas stained positive for this marker. The aim of this study was to assess
      the value of CD73 in differentiating ITB from CD granulomas in a South African
      cohort. METHODS: Patients with confirmed CD or ITB were identified from a
      pathology database. Tissue sections were reviewed by a pathologist to confirm the
      presence of granulomas. These were then stained with a mouse monoclonal anti-CD73
      antibody. The slides were examined together by a pathologist and
      gastroenterologist in a blinded manner for anti-CD73 staining around granulomas.
      RESULTS: Ninety six cases were available for analysis; 50 cases of ITB and 46
      cases of CD. Thirty percent of CD granulomas (14/46) stained positive for CD73,
      whereas CD73 positivity was seen in 52% (26/50) of cases of ITB. This was
      statistically significant (OR 2.48, 95% CI 1.1-5.72, p = .03). The area under the
      curve (AUC) was 0.61. Sensitivity of CD73 in predicting ITB was 52% and
      specificity was 70%. Overall CD73 staining of granulomas correctly classified
      only 60% of cases. CONCLUSIONS: In our study we have shown that significantly
      more patients with ITB express CD73 in their granulomas than those with CD.
      However the relatively poor sensitivity, specificity and AUC make this test
      unlikely to be of value in our clinical practice.

PMID- 30295113
TI  - Participants' experiences of an Internet-based cognitive behavioural therapy
      intervention for tinnitus.
AB  - OBJECTIVE: This study aimed to explore participants' experiences after
      undertaking an Internet-based cognitive behavioural therapy intervention (ICBT)
      for tinnitus. DESIGN: Semi-structured telephone interviews were conducted 6-8
      months after participants undertook the ICBT intervention. Qualitative thematic
      analysis was used to interpret the interview data. STUDY SAMPLE: A purposeful
      sampling strategy was used to identify a diverse range of participants. Semi
      structured interviews were carried out with 15 participants. The mean age was
      58.5 years, 7 men and 8 women participated. RESULTS: The analysis generated the
      following main themes: (1) expectations and motivation for doing the
      intervention, (2) experiences of the intervention, (3) intervention engagement
      and (4) intervention effects. Most participants' expectations were hopeful that
      the intervention would lessen the impact of their tinnitus. Aspects of the
      intervention that were beneficial, as well as difficult, were identified together
      with the impact they had on engagement. Intervention effects were evident on both
      tinnitus and activities of daily life. CONCLUSIONS: The benefits described by
      participants indicate the potential of ICBT as an alternate form of intervention
      delivery. The difficulties that hampered engagement need to be addressed to
      enhance the application and to optimise the clinical acceptability of ICBT for
      tinnitus.

PMID- 30295114
TI  - Long-term survival in patients with epithelial ovarian cancer following
      cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).
AB  - OBJECTIVE: Despite a high response rate to first-line therapy, prognosis of
      epithelial ovarian carcinoma (EOC) remains poor. The objective of the present
      study was to evaluate the frequency of long-term survivors and to identify the
      prognostic factors associated with long-term survival in a French cohort of 566
      patients. METHODS: Patients treated with cytoreductive surgery (CRS) and
      hyperthermic intraperitoneal chemotherapy (HIPEC) for EOC in 13 French centers
      between 1991 and 2010 were included. Long-term survivors were defined as patients
      who survived more than 5 years after HIPEC and CRS, irrespective of relapse.
      RESULTS: Seventy-eight long-term survivors were analyzed. The median follow-up
      was 74 months. Median age at the time of first HIPEC was 55.4 years (range [22.6
      77.6]. Seven patients had advanced EOC and 71 patients had recurrent EOC (37
      patients had platinum-resistant EOC and 32 had platinum-sensitive disease). More
      than half of the long-term survivors had high-grade serous ovarian cancer
      (HGSOC). In univariate analysis, age >=50 years (p = .004), peritoneal cancer
      index (PCI) <= 8 (p = .049) and CA-125 < 100 (p = .02) were associated with long
      term survival. There was a trend towards an association between higher CC-score
      and long-term survival (p = .057). CONCLUSION: Age >=50 years, PCI <=8 and CA125
      < 100 were associated with long-term survival in univariate analysis. There was a
      trend towards the significance of CC-score. Platinum-status was not associated
      with long-term survival.

PMID- 30295115
TI  - Efficacy of radio-hyperthermo-chemotherapy as salvage therapy for recurrent or
      residual malignant soft tissue tumors.
AB  - BACKGROUND: Recurrence after wide excision or residual tumor after an unplanned
      excision of a malignant soft tissue sarcoma (STS) is a complex problem, due to a
      higher recurrence rate and poorer survival rate compared with primary resection.
      Regional hyperthermia was used, with the expectation that it will enhance the
      anti-tumor effects of chemotherapy and radiotherapy. This study aimed to assess
      the efficacy of neoadjuvant concomitant radiotherapy, hyperthermia, and
      chemotherapy (RHC) for salvage of recurrent or residual malignant STS. METHODS:
      We identified 64 patients with recurrent or residual STS treated between 1994 and
      2013. After excluding those with low-grade malignancy, with recurrent bone tumor
      in the soft tissues, with truncal STS, and who declined to participate, 23
      patients (7 with recurrence and 16 with residual tumor) underwent RHC. The
      histologic diagnoses were undifferentiated pleomorphic sarcoma (n = 11), synovial
      sarcoma (n = 3), leiomyosarcoma and myxoid liposarcoma (n = 2 each), and other
      histologic types. As primary outcomes, the 5-year overall survival (OS), distant
      metastasis-free survival (D-MFS), and local control (LC) rates were evaluated by
      Kaplan-Meier analysis. RESULTS: The median follow-up period was 112.3 months. The
      5-year OS, D-MFS, and LC were 86.4%, 77.4%, and 86.7%, respectively. In the
      univariate analysis, tumor depth was considered as a negative prognostic factor
      for OS and D-MFS, and a positive margin was also a negative prognostic factor for
      OS, D-MFS LC with retained on Cox proportional hazards model in OS, and D-MFS.
      CONCLUSION: RHC is an effective option for salvage treatment of recurrent and
      residual STS.

PMID- 30295116
TI  - Effects of serotonin depletion and dopamine depletion on bimodal divided
      attention.
AB  - OBJECTIVES: This study aimed to explore the effects of acute phenylalanine
      tyrosine depletion (APTD) and acute tryptophan depletion (ATD) on bimodal divided
      attention. A balanced amino acid mixture (BAL) served as control condition.
      METHODS: 54 healthy adults (age: M = 23.8 years) were randomly assigned to APTD,
      ATD or BAL in a double-blind, between-subject approach. Divided attention was
      assessed after 4 hours. Blood samples were taken before and 6 hours after
      challenge intake. RESULTS: Amino acid concentrations following challenge intake
      significantly decreased (all p <= .01). There was a significant difference in the
      mean reaction time (RT) towards auditory stimuli, but not towards visual stimuli
      between the groups. Post-hoc comparison of mean RT's (auditory stimuli) showed a
      significant difference between ATD (RT = 604.0 ms, SD = 56.9 ms) and APTD (RT =
      556.4 ms, SD = 54.2 ms; p = .037), but no RT-difference between ATD and BAL or
      APTD and BAL (RT = 573.6 ms, SD = 45.7 ms). CONCLUSIONS: The results indicate a
      possible dissociation between the effects of a diminished brain 5-HT and DA
      synthesis on the performance in a bimodal divided attention task. The difference
      was exclusively observed within the RT towards auditory signals.

PMID- 30295117
TI  - Guide the way: Tutored reflection facilitates professional identity formation.

PMID- 30295118
TI  - Meeting Abstracts - Academy of Managed Care Pharmacy Nexus 2018.
AB  - AMCP Nexus 2018: Preparing for the Next Generation of Care in Orlando, Florida,
      is expected to attract more than 2,400 managed care pharmacists and other health
      care professionals who manage and evaluate drug therapies, develop and manage
      networks, and work with medical managers and information specialists to improve
      the care of all individuals enrolled in managed care programs. The AMCP Abstracts
      program provides a forum through which authors can share their insights and
      outcomes of advanced managed care practice. Poster author presentations for AMCP
      Nexus 2018 are scheduled for Wednesday, October 24, from 12:30 pm to 2:30 pm. For
      each poster, at least one author will be available during the poster
      presentations to discuss findings. Posters will also be displayed on Tuesday,
      October 23, from 4:15 pm to 6:10 pm, during the opening night reception in the
      Exchange, and on Wednesday, October 24, from 11:30 am to 2:45 pm. Podium
      presentations for the Platinum award-winning abstracts are Tuesday, October 23,
      from 12:45 pm to 2:15 pm. Professional abstracts that have been reviewed are
      published in the Journal of Managed Care & Specialty Pharmacy's Meeting Abstracts
      supplement.

PMID- 30295119
TI  - Microbubble-assisted MRI-guided focused ultrasound for hyperthermia at reduced
      power levels.
AB  - PURPOSE: Ultrasound contrast agent microbubbles were combined with magnetic
      resonance imaging (MRI)-guided focused ultrasound (MRgFUS) as a means to achieve
      mild hyperthermia at reduced power levels. METHODS: MRgFUS hyperthermia (42
      degrees C for 20 min) was evaluated in rabbit thigh muscle or Vx2 tumors using
      infusions of microbubbles (Definity, 20 uL/kg) or saline (sham) administered over
      5 min. The impact of treatments on drug uptake was assessed with liposomal
      doxorubicin (Caelyx, 2.5 mg/kg). Applied power levels before and after the
      injection of microbubbles or saline were compared, and drug uptake was evaluated
      with fluorometry of tissues harvested 24 hr post-treatment. RESULTS: MRgFUS
      hyperthermia in muscle and tumors resulted in accurate temperature control (mean
      =42.0 degrees C, root mean square error (RMSE) = 0.3 degrees C). The power
      dropped significantly following the injection of microbubbles in muscle and
      tumors compared to exposures without microbubbles (-21.9% +/- 12.5% vs -5.9% +/-
      7.8%, p = .009 in muscle; -33.8% +/- 9.9% vs -3.0% +/- 7.2%, p < .001 in tumors).
      Cavitation monitoring indicated emission of subharmonic, ultraharmonic, and
      elevated levels of fourth to sixth harmonic frequencies following microbubble
      injection. The drug delivery was elevated significantly in muscle with the use of
      microbubble-assisted relative to conventional heating (0.5 +/- 0.5 ng/mg vs 0.20
      +/- 0.04 ng/mg, p = .05), whereas in tumors similar levels were found (11 +/- 3
      ng/mg vs 16 +/- 4 ng/mg, p = .13). CONCLUSIONS: The finding that microbubbles
      reduce the applied power requirements for hyperthermia has considerable clinical
      implications. The elevated levels of drug found in muscle but not tumor tissue
      suggest a complex interplay between the heating effects of microbubbles with
      those of enhanced permeabilization and possible vascular damage.

PMID- 30295120
TI  - Early versus late stage schizophrenia. What markers make the difference?
AB  - OBJECTIVES: To identify the psychopathological, cognitive, functional, physical
      health and inflammatory markers that differentiate between early-stage
      schizophrenia (ESSCH) and late-stage schizophrenia (LSSCH). METHODS: Cross
      sectional, naturalistic study of 104 patients with SCH. The sample was divided in
      two groups: 35 ESSCH (<=7 years' duration of illness) and 69 LSSCH (>10 years'
      duration of illness). STATISTICAL ANALYSIS: chi-square test and Student's t-test
      and ANCOVA (or Quade test) controlling for age, sex, BMI and number of
      cigarettes/day. Finally, a binomial logistic regression was made. RESULTS: ESSCH
      show greater negative symptom severity (t = 2.465, p = 0.015), lower levels of
      IkappaBalpha (F = 7.644, p = 0.007), were more frequently classified as normal
      weight (40% vs 18.8%, p = 0.032) compared with LSSCH. The binomial logistic
      regression model included age (B = 0.127, p = 0.001) and IkappaBalpha (B = 0.025,
      p = 0.002) and accounted for 38.9% of the variance (model df =7, chi-square
      =41.841, p < 0.0001). CONCLUSIONS: Age and IkappaBalpha are the unique markers
      that differentiate between ESSCH patients whose duration of illness is less than
      7 years and LSSCH patients. These results support the hypothesis of toxicity of
      episodes and highlight the importance of preventing new episodes.

PMID- 30295121
TI  - Correction.

PMID- 30295122
TI  - Continuous, label-free, 96-well-based determination of cell migration using
      confluence measurement.
AB  - Cellular migration is essential in diverse physiological and pathophysiological
      processes. Here, we present a protocol for quantitative analysis of migration
      using confluence detection allowing continuous, non-endpoint measurement with
      minimal hands-on time under cell incubator conditions. Applicability was tested
      using substances which enhance (EGF) or inhibit (cytochalasin D, ouabain)
      migration. Using a gap-closure assay we demonstrate that automated confluence
      detection monitors cellular migration in the 96-well microplate format.
      Quantification by % confluence, % cell free-area or % confluence in cell-free
      area against time, allows detailed analysis of cellular migration. The study
      describes a practicable approach for continuous, non-endpoint measurement of
      migration in 96-well microplates and for detailed data analysis, which allows for
      medium/high-throughput analysis of cellular migration in vitro.

PMID- 30295123
TI  - Results of tenorrhaphy with early rehabilitation for acute tear of Achilles
      tendon.
AB  - BACKGROUND: For the treatment of acute Achilles tendon rupture, early
      rehabilitation after surgical repair is believed to be a useful method. The
      purpose of this study was to evaluate the outcome of open tenorrhaphy followed by
      early rehabilitation. METHODS: A total of 112 patients who underwent open repair
      and early rehabilitation for acute Achilles tendon rupture from January 2003 to
      March 2015 were retrospectively reviewed. These 112 patients (80 men, 32 women)
      had an average age of 43.1 years (22-62 years), and the mean follow-up period was
      91.8 months (12-171 months). A short leg cast was applied postoperatively for an
      average of 16.5 days (12-20 days). The mean duration of bracing was 6.9 weeks (6
      8 weeks). Each patient was assessed based on range of motion, single heel raising
      test, calf circumference compared to the contralateral limb, ability to return to
      previous activity, the Arner-Lindholm scale, and the American orthopaedic foot
      and ankle society (AOFAS) hind foot scale. Isokinetic plantar flexion power was
      also checked. RESULTS: All patients were fully satisfied (AOFAS >= 90) with the
      treatment results, and 96 patients were able to return to their previous athletic
      activities. As assessed by the Arner-Lindholm scale, 103 cases were rated as
      excellent and the other 9 cases were rated as good. At the 1-year follow-up
      period, single heel raise and hopping was possible in every patient. Compared to
      the contralateral side, 10 subjects (8.9%) had minor limitation of dorsiflexion
      motion, and an average of 1.6 cm calf circumference difference without functional
      disabilities. There were no major complications such as re-rupture, nerve injury,
      or infection. CONCLUSION: For acute Achilles tendon ruptures, open surgical
      repair with optimal length restoration, followed by earlier rehabilitation
      results in good functional outcomes and a successful return to pre-injury levels
      of physical activity without major complications. LEVEL OF EVIDENCE: Level IV.

PMID- 30295124
TI  - Endosomal microautophagy is an integrated part of the autophagic response to
      amino acid starvation.
AB  - Starvation is a fundamental type of stress naturally occurring in biological
      systems. All organisms have therefore evolved different safeguard mechanisms to
      cope with deficiencies in various types of nutrients. Cells, from yeast to
      humans, typically respond to amino acid starvation by initiating degradation of
      cellular components by inducing autophagy. This degradation releases metabolic
      building blocks to sustain essential core cellular processes. Increasing evidence
      indicates that starvation-induced autophagy also acts to prepare cells for
      prolonged starvation by degrading key regulators of different cellular processes.
      In a recent study, we found that within the first hours of amino acid starvation
      cells elicit an autophagic response causing rapid degradation of specific
      proteins. The response is executed independently of both MTOR and canonical
      macroautophagy. Based on RNAi-mediated knockdown of essential components of the
      Endosomal Sorting Complex Required for Transport (ESCRT) machinery and electron
      microscopy we conclude that the response relies on some sort of endosomal
      microautophagy, hence vesicle budding into endosomes. Substantiated by the
      different substrates that are selectively degraded by this novel pathway we
      propose that the response predominantly acts to prepare cells for prolonged
      starvation. Intriguingly, this includes shutting down selective macroautophagy in
      preparation for a massive induction of bulk macroautophagy.

PMID- 30295125
TI  - Development of custom RF coils for use in a small animal platform for magnetic
      resonance-guided focused ultrasound hyperthermia compatible with a clinical MRI
      scanner.
AB  - Three different magnetic resonance imaging (MRI) coils were developed and
      assessed for use with an experimental platform designed to generate hyperthermia
      in mice using magnetic resonance-guided focused ultrasound (MRgFUS). An ergonomic
      animal treatment bed was integrated with MRI coils. Three different coil designs
      optimized for small targets were tested, and performance in targeting and
      conducting accurate temperature imaging was evaluated. Two transmit/receive
      surface coils of different diameters (4 and 7 cm) and a transmit-only/receive
      only (TORO) coil were used. A software platform was developed to provide real
      time targeting and temperature maps and to deliver controlled ultrasound
      exposure. MR thermometry was conducted on different targets, including fresh
      chicken breasts and mouse cadavers. Multiple experiments were performed in which
      tissues were targeted with high reproducibility. The TORO coil was the most
      resilient to temperature drift, resulting in an increase in the calculated
      temperature of 0.29 +/- 0.12  degrees C, compared to 1.27 +/- 0.13  degrees C and
      0.47 +/- 0.04  degrees C for the medium and small coils, respectively. Controlled
      closed-loop hyperthermia exposure was successfully performed with all three
      coils. Considering all assessments, the TORO coil exhibited the best overall
      performance for thermometry acquisition when accounting for stability, precision,
      temperature spread and resilience to temperature drift. B1 maps of the three
      coils confirmed that the TORO coil exhibited the most homogeneous B1 field, which
      explained the improved thermometry performance. The use of coils specifically
      designed for small targets within the proposed experimental platform allowed
      accurate thermometry during hyperthermia.

PMID- 30295126
TI  - Innate/inflammatory bioregulation and clinical effectiveness of whole-body
      hyperthermia (balneotherapy) in elderly patients with osteoarthritis.
AB  - OBJECTIVES: Balneotherapy with mud application (mud therapy) is a common
      hydrothermal intervention for the treatment and rehabilitation of elderly
      patients with osteoarthritis, leading to anti-inflammatory effects. The main
      purpose of this investigation was to study a role for regulatory T cells in these
      anti-inflammatory effects. The second objective was to assess whether the
      neutrophil-mediated innate response is affected by these anti-inflammatory
      effects. METHODS: Thirty-six elderly patients with knee osteoarthritis underwent
      a 10-day cycle of balneotherapy at a spa center. They received daily sessions of
      whole-body mud therapy at 40-42  degrees C, using mineral-medicinal water and
      mud. IL-8 and TGF-beta serum concentrations, percentage of circulating CD4+ CD25+
      FOXP3+ and CD8+ CD28- regulatory T cells, and neutrophil phagocytic capacity were
      evaluated at baseline and at the end of the intervention. Clinical assessments
      included knee flexion and extension angle, pain, stiffness, physical function and
      health-related quality of life. RESULTS: All clinical outcomes significantly
      improved. Circulating concentrations of IL-8 and TGF-beta decreased, which
      correlated with decreased pain and improved knee flexion, respectively.
      Percentage of CD4+ regulatory T cells decreased, whereas CD8+ regulatory T cells
      increased. Neutrophil functional capacity increased. CONCLUSIONS: Balneotherapy
      with mud application was effective in the management of osteoarthritis symptoms.
      The anti-inflammatory effect mediated by cytokines contributed to the improvement
      in pain and joint function; and changes in the circulating percentage of
      regulatory T cells seem to be involved in the anti-inflammatory effects.
      Improvement in neutrophil function after mud therapy reflects an optimal
      bioregulatory effect on the inflammatory and innate responses.

PMID- 30295128
TI  - A highly stable laccase from Bacillus subtilis strain R5: gene cloning and
      characterization.
AB  - : The gene encoding copper-dependent laccase from Bacillus subtilis strain R5 was
      cloned and expressed in Escherichia coli. Initially the recombinant protein was
      produced in insoluble form as inclusion bodies. Successful attempts were made to
      produce the recombinant protein in soluble and active form. The laccase activity
      of the recombinant protein was highly dependent on the presence of copper ions in
      the growth medium and microaerobic conditions during protein production. The
      purified enzyme exhibited highest activity at 55  degrees C and pH 7.0. The
      recombinant protein was highly thermostable, albeit from a mesophilic source,
      with a half-life of 150 min at 80  degrees C. Similar to temperature, the
      recombinant protein was stable in the presence of organic solvents and protein
      denaturants such as urea. Furthermore, the recombinant protein was successfully
      utilized for the degradation of various synthetic dyes reflecting its potential
      use in treatment of wastewater in textile industry. ABBREVIATIONS: ABTS,2,2'
      azino-bis(3-ethylbenzothiazoline-6-sulphonic acid; CBB, Coomassie brilliant blue;
      SGZ, syringaldazine; DMP, 2,2-dimethoxy phenol.

PMID- 30295127
TI  - RBM-5 modulates U2AF large subunit-dependent alternative splicing in C. elegans.
AB  - A key step in pre-mRNA splicing is the recognition of 3' splicing sites by the
      U2AF large and small subunits, a process regulated by numerous trans-acting
      splicing factors. How these trans-acting factors interact with U2AF in vivo is
      unclear. From a screen for suppressors of the temperature-sensitive (ts)
      lethality of the C. elegans U2AF large subunit gene uaf-1(n4588) mutants, we
      identified mutations in the RNA binding motif gene rbm-5, a homolog of the tumor
      suppressor gene RBM5. rbm-5 mutations can suppress uaf-1(n4588) ts-lethality by
      loss of function and neuronal expression of rbm-5 was sufficient to rescue the
      suppression. Transcriptome analyses indicate that uaf-1(n4588) affected the
      expression of numerous genes and rbm-5 mutations can partially reverse the
      abnormal gene expression to levels similar to that of wild type. Though rbm-5
      mutations did not obviously affect alternative splicing per se, they can suppress
      or enhance, in a gene-specific manner, the altered splicing of genes in uaf
      1(n4588) mutants. Specifically, the recognition of a weak 3' splice site was more
      susceptible to the effect of rbm-5. Our findings provide novel in vivo evidence
      that RBM-5 can modulate UAF-1-dependent RNA splicing and suggest that RBM5 might
      interact with U2AF large subunit to affect tumor formation.

PMID- 30295129
TI  - Effect of mutation of C-terminal and heme binding region of Arabidopsis catalase
      on the import to peroxisomes.
AB  - : We evaluated the import of Arabidopsis catalase to peroxisomes under homogenous
      transient expression. The amino acids at -11 to -4 from the C-terminus are
      necessary for catalase import. The results are in agreement with the previous
      work under stable expression. We first demonstrate that heme-binding sites are
      important for peroxisomal import, suggesting the importance of catalase folding.
      ABBREVIATIONS: AtCat: Arabidopsis catalase; PTS: peroxisomal targeting signal;
      PEX: Peroxin.

PMID- 30295131
TI  - Quantitation and sensory properties of three newly identified pyroglutamyl
      oligopeptides in sake.
AB  - Three new peptides: (pGlu)L-ethyl, (pGlu)LFGP-ethyl and (pGlu)LFNP-ethyl, were
      identified in the search for pyroglutamyl oligopeptide ethyl esters in sake. The
      ethyl esterified peptides in sake were quantitated using stable isotope dilution
      analysis and additional quantitation of (pGlu)L was performed using an external
      standard method. The concentrations of (pGlu)L-ethyl and (pGlu)L in 33 commercial
      sake samples ranged from 0.16 to 1.57 mg/L and 1.49 to 7.55 mg/L, respectively.
      The sensory properties of the pyroglutamyl oligopeptide ethyl esters and
      corresponding non-esterified peptides were examined: the estimated difference
      threshold of (pGlu)L (2.0 mg/L) and (pGlu)L-ethyl (0.267 mg/L) was exceeded in 32
      and 26 samples, respectively. Estimated thresholds of (pGlu)LFGP-ethyl and
      (pGlu)LFNP-ethyl were often lower than the levels in quantitated sake samples.
      The sensory effects of these pyroglutamyl dipeptides on a model sake quality may
      be negative because of their unpleasant taste, however, (pGlu)LFNP-ethyl may be
      positive because of its mild taste.

PMID- 30295130
TI  - Unusual Stability Exhibited by (AT)XN12(AT)Y Motif Associated With High Fetal
      Hemoglobin Levels.
AB  - Quasi-palindromic sequences (AT)XN12(AT)Y present in HS2 (hypersensitive site) of
      the human beta-globin locus are known to be significantly associated with
      increased fetal hemoglobin (HbF) levels. High HbF levels in some adults arise due
      to pathological conditions such as sickle cell disease and beta-thalassemia.
      However, elevated levels of HbF are also associated with a reducing morbidity and
      mortality in patients with beta-thalassemia and thus ameliorate the severity of
      the disease. Using gel-electrophoresis, ultraviolet (UV)-thermal denaturation and
      circular dichroism (CD) techniques, we demonstrated that it exhibits a hairpin
      duplex equilibrium. Intramolecular species (hairpin) were observed in both low as
      well as high salt concentration in gel assay studies displaying the unusual
      stability of intramolecular species even at the high counter-ion concentration.
      Unusual stability of hairpin secondary structures was also demonstrated by the
      monophasic nature of the melting profiles for the oligonucleotides which
      persisted at low as well as high salt and oligomer concentrations. Change in CD
      spectra as a function of oligomer concentration indicates that the bimolecular
      duplex formation is selectively favored over monomolecular hairpin formation at
      and above 9 uM oligomer concentration. Thus, we hypothesize that imperfect
      inverted repeat sequence (AT)XN12(AT)Y of HS2 of beta-globin gene LCR form the
      unusually stable hairpins which may result in the formation of a cruciform
      structure that may be recruited for binding by various nuclear proteins that
      could result in elevated HbF levels.

PMID- 30295132
TI  - Memory experts' beliefs about repressed memory.
AB  - What we believe about how memory works affects the decisions we make in many
      aspects of life. In Patihis, Ho et al. [Patihis, L., Ho, L. Y., Tingen, I. W.,
      Lilienfeld, S. O., & Loftus, E. F. (2014). Are the "memory wars" over? A
      scientist-practitioner gap in beliefs about repressed memory. Psychological
      Science, 25, 519-530.], we documented several group's beliefs on repressed
      memories and other aspects of how memory works. Here, we present previously
      unreported data on the beliefs of perhaps the most credible minority in our
      dataset: memory experts. We provide the statistics and written responses of the
      beliefs for 17 memory experts. Although memory experts held similarly sceptical
      beliefs about repressed memory as other research-focused groups, they were
      significantly more sceptical about repressed memory compared to practitioners,
      students and the public. Although a minority of memory experts wrote that they
      maintained an open mind about repressed memories - citing research such as
      retrieval inhibition - all of the memory experts emphasised the dangers of memory
      distortion.

PMID- 30295133
TI  - British Journal of Biomedical Science in 2018: what have we learned?
AB  - In 2018 the British Journal of Biomedical Science published one guideline (in
      reproductive science) and 40 research articles in the various disciplines the
      comprise biomedical science. The latter were 24 original articles and 16 'In
      Brief' short reports. Of these, 23 are of note to only one of the sub-disciplines
      (seven each to biochemists and microbiologists, six to cell pathologists, and one
      each to cytologists, immunologists and reproductive scientists). Reflecting the
      increasing complexity of laboratory science, thirteen papers crossed one boundary
      (three papers each relevant to biochemists and immunologists, and to
      haematologists and biochemists), whilst four papers were relevant to three or
      more disciplines. Indeed, biochemical techniques were used in 18 papers,
      microbiological techniques in 9, whilst histopathology was relevant to 11 papers.
      Notably, 20 papers used techniques in chromosome analysis and molecular genetics.
      The present report will summarise key aspects of these publications that are of
      greatest relevance to laboratory scientists.

PMID- 30295134
TI  - Changes of mediolateral soft tissue gaps in total knee arthroplasty after
      suturing medial extensor in navigation.
AB  - PURPOSE: Aim is to investigate the changes of mediolateral soft tissue gaps in
      total knee arthroplasty (TKA) after suturing medial extensor. METHODS AND
      MATERIALS: We compared the differences of medial and lateral gap values that were
      shown by the computer navigation at 0 degrees , 45 degrees , 90 degrees , and 120
      degrees  knee flexion during patella in situ and during patella repaired by a
      towel clip on two constant sites. Fifty consecutive knees (43 patients) scheduled
      for TKA due to varus knee osteoarthritis, from February 2017 to May 2017, were
      enrolled in this prospective study. RESULTS: The medial gaps with patella
      repaired were significantly lower ( p < 0.05) than the medial gaps with patella
      in situ at 45 degrees , 90 degrees , and 120 degrees  knee flexion. Differences
      in the medial gap were largest at 90, with the difference of 0.87 mm. Twenty-four
      of 50 cases (48%) showed medial gap differences of 1 mm or over, and 13 of 50
      cases (26%) showed medial gap differences of 2 mm or over. The variation in the
      medial gap at 90 degrees  following patellar repair showed significant
      association (correlation coefficient = 0.78, p = 0.001) with the difference
      between medial and lateral gaps (medial gap - lateral gap) at 90 degrees  of
      patella in situ. At 90 degrees  knee flexion, when the medial and lateral gap
      difference in patella in situ was 1 mm or less, 73.5% (25/34) of the cases showed
      variation in the medial gap of less than 1 mm after patellar repair. CONCLUSION:
      During TKA, while measuring the medial gap with patella in situ, overestimation
      might occur, especially in the position of knee flexion. Thus, reevaluation using
      towel clips should be considered when the medial and lateral gap difference is 1
      mm or larger when patella in situ during evaluation of the medial and lateral
      gaps at 90 degrees  knee flexion.

PMID- 30295135
TI  - Nurses developing confidence and competence in telehealth: results of a
      descriptive qualitative study.
AB  - BACKGROUND: The widespread use of telehealth brings benefits to improve access to
      healthcare for rural and remote populations. OBJECTIVE: This study explores what
      nurses considered important to confidently and competently participate in
      telehealth. DESIGN: A descriptive qualitative approach was selected. METHODS:
      Nine New Zealand Registered Nurses who worked in different clinical settings who
      use telehealth were identified through snowball sampling, and participated in
      single semi-structured interviews, which were thematically analysed using a
      general inductive approach. FINDINGS: The nurses' experience of using telehealth,
      from novice to becoming more proficient, was the main theme identified, with sub
      themes of: Initial use of telehealth, hands-on training, specialty experience,
      mentorship and technological know-how. The confidence of nurses using telehealth
      in this study may reflect their clinical nursing experience. CONCLUSION:
      Recommendations include the need for more telehealth education and preparation,
      including incorporating telehealth in under and postgraduate nursing programmes.
      Additionally, specific telehealth nursing competencies are warranted.

PMID- 30295136
TI  - Risk of patella baja after opening-wedge high tibial osteotomy.
AB  - PURPOSE: Medial opening-wedge high tibial osteotomy (OWHTO) induces a lower
      patellar position, and the subsequent degree of patellar movement may not be
      predicted preoperatively. The purpose of this study was to clarify the
      relationship between preoperative and postoperative patellar height based on the
      correction angle of OWHTO and to create a formula to predict the appearance of
      patella baja following OWHTO. MATERIALS AND METHODS: Seventy-five knees with
      varus knee osteoarthritis treated with OWHTO were included in this study. The
      Caton-Deschamps index was used to evaluate patellar height preoperatively and
      postoperatively, and the cut-off value for preoperative parameters was determined
      by a receiver operating characteristic curve to determine the risk ratio for
      postoperative patella baja. RESULTS: The Caton-Deschamps index significantly
      decreased from 0.93 to 0.77 after OWHTO ( p < 0.01). The OWHTO correction angle
      negatively correlated with the delta Caton-Deschamps index ( r = -0.44, p <
      0.01), and a 1.7% decrease in the Caton-Deschamps index was shown with a 1
      degrees  correction angle. Receiver operating characteristic curve analysis
      revealed that a Caton-Deschamps index of 0.8 was the cutoff for OWHTO; knees with
      a preoperative Caton-Deschamps index of < 0.8 tended to develop patella baja
      after OWHTO, with a risk ratio of 9.5 (95% confidence interval [4.3-20.7]).
      CONCLUSIONS: OWHTO can induce patella baja, and a 1.7% decrease in the Caton
      Deschamps index was shown with a 1 degrees -correction angle. A preoperative
      Caton-Deschamps index < 0.8 should be considered a risk factor for postoperative
      patella baja. LEVEL OF EVIDENCE: Retrospective study, Level IV.

PMID- 30295138
TI  - The Impact of Chronic Ozone and Particulate Air Pollution on Mortality in
      Patients With Sepsis Across the United States.
AB  - OBJECTIVE: The impact of chronic exposure to air pollution on mortality in
      patients with sepsis is unknown. We attempted to quantify the relationship
      between air pollution, notably excess ozone, and particulate matter (PM), with in
      hospital mortality in patients with sepsis nationwide. METHODS: The 2011
      Nationwide Inpatient Sample (NIS) was linked with ambient air pollution data from
      the Environmental Protection Agency for both 8-hour ozone exposure and annual
      mean 2.5-micron PM (PM2.5) pollution levels. A validated severity of illness
      model for sepsis using administrative data was used to control for sepsis
      severity. RESULTS: The records of 8 023 590 hospital admissions from the 2011 NIS
      sample were analyzed. Of these, there were 444 928 patients who met the Angus
      definition of sepsis, treated in hospitals for which air pollution data were
      available. The cohort had an overall mortality of 11.2%. After adjustment for
      severity of sepsis, increasing exposure to ozone pollution was associated with
      increased risk of mortality (odds ratio [OR]: 1.04 for each 0.01 ppm increase,
      95% confidence interval [CI]: 1.03-1.05; P < .01). Particulate matter was not
      associated with mortality (OR: 0.99 for each 5 ug/m3 increase, 95% CI: 0.97-1.01;
      P = .28). When stratified by sepsis source, ozone pollution had a higher impact
      on patients with pneumonia (OR: 1.06, 95% CI: 1.04-1.08; P < .01) compared to
      those patients without pneumonia (OR: 1.02, 95% CI: 1.01-1.03; P < .01).
      CONCLUSION: Exposure to increased levels of ozone but not particulate air
      pollution was associated with higher risk of mortality in patients with sepsis.
      This association was strongest in patients with pneumonia but persisted in all
      sources of sepsis. Further work is needed to understand the relationship between
      ambient ozone air pollution and sepsis outcomes.

PMID- 30295137
TI  - Impact of ascending aortic, hemiarch and arch repair on early and long-term
      outcomes in patients with Stanford A acute aortic dissection.
AB  - BACKGROUND:: Stanford A acute aortic dissection (AAD) is a life-threatening
      emergency associated with major morbidity and mortality. The aim of this study
      was to compare outcomes of three different surgical approaches in patients with
      Stanford A AAD. METHODS:: From January 2006 to March 2015 a total of 240
      consecutive patients with diagnosed Stanford A AAD underwent elective, isolated
      surgical aortic repair in our centre. Patients were divided into three groups
      according to the extent of surgical repair: isolated replacement of the ascending
      aorta, hemiarch replacement and total arch replacement. Patients were followed up
      for up to 9 years. After univariate analysis multinomial logistic regression was
      performed for subgroup analysis. Baseline characteristics and endpoints as well
      as long-term survival were analysed. RESULTS:: There were no statistically
      significant differences among the three groups in terms of demographics and
      preoperative baseline and clinical characteristics. Incidence of in-hospital
      stroke ( p = 0.034), need for reopening due to bleeding ( p = 0.031) and in
      hospital mortality ( p = 0.017) increased significantly with the extent of the
      surgical approach. There was no statistical difference in terms of long-term
      survival ( p = 0.166) among the three groups. Applying multinomial logistic
      regression for subgroup analysis significantly higher odds for stroke ( p =
      0.023), reopening for bleeding ( p = 0.010) and in-hospital mortality ( p =
      0.009) for the arch surgery group in comparison to the ascending aorta surgery
      group as well as significantly higher odds for stroke ( p = 0.029) for the total
      arch surgery group in comparison to the hemiarch surgery group were identified.
      CONCLUSIONS:: With Stanford A AAD the incidence of perioperative complications
      increased significantly with the extent of the surgical approach. Subgroup
      analysis and long-term follow up in patients undergoing isolated ascending or
      hemiarch surgery showed a lower incidence of cerebrovascular events compared with
      surgery for total arch replacement.

PMID- 30295139
TI  - Platelet-rich plasma decreases fibroblastic activity and woven bone formation
      with no significant immunohistochemical effect on long-bone healing: An
      experimental animal study with radiological outcomes.
AB  - PURPOSE: This study aimed to analyze the immunohistochemical effect of platelet
      rich plasma (PRP) on healing of long-bone fractures in terms of bone
      morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), the
      Ki-67 proliferation index, and radiological and histological analyses. METHODS:
      Sixteen adult rabbits, whose right femoral diaphysis was fractured and fixed with
      Kirschner wires, were randomly divided into two groups, control and PRP (groups A
      and B, respectively). PRP was given to group B at 1 week postoperatively, and all
      animals were euthanized after 12 weeks. Radiographic evaluations were performed
      periodically. Cortical callus formation, chondroid and woven bone area
      percentages, osteoblastic and fibroblastic activities, and mature bone formation
      were examined. The depths of BMP-2 and VEGF staining were measured. The Ki-67
      proliferation index was also calculated. RESULTS: The mean radiological union
      score of group B was significantly higher than that of group A. There were also
      statistically significant differences between groups A and B in terms of cortical
      callus formation, woven bone area percentage, fibroblast proliferation, and
      mature bone formation. Group B had significantly more cortical callus and mature
      bone formation with less woven bone and fibroblast proliferation.
      Immunohistochemical analysis revealed no statistically significant difference
      between the groups in terms of BMP-2 and VEGF staining and the Ki-67 index.
      CONCLUSIONS: PRP had no effect on BMP-2 or VEGF levels with no increase in the Ki
      67 proliferation index, although its application had a positive effect on bone
      healing by increasing callus and mature bone formation with decreased woven bone
      and fibroblast proliferation.

PMID- 30295140
TI  - Over expression of PI3K-AkT reduces apoptosis and increases prostate size in
      benign prostatic hyperplasia.
AB  - INTRODUCTION: Even though the role of the phosphatidylinositol 3-kinase
      (PI3K)/AKT pathways and apoptosis has been well established in prostate cancer,
      there are no studies regarding alteration in the gene expression of PI3K/AKT
      pathway and protein expression of apoptotic components and their association with
      prostate size in Benign prostatic hyperplasia (BPH). Hence the study was designed
      to analyze the expression pattern of PI3K/AKT and apoptotic components in
      patients with BPH. MATERIALS AND METHODS: A total of 27 BPH patients aged between
      55 and 75 years were recruited in the study and prostatic tissues were obtained
      after transurethral resection of the prostate. Gene expression levels of PI3K and
      AKT were assessed by q-PCR. Apoptotic components like BcL-2, caspase-3, caspase
      9, BAD, and p-BAD were analyzed by western blotting and immunohistochemistry.
      RESULTS: Gene expression of PI3K (p85-A) (p = .02), AKT1 (p < .01) and AKT2 (p <
      .01), and protein expression of BcL-2 (p < .01) and caspase-9 (p < .01) were
      significantly increased in BPH patients with larger prostate size compared to
      smaller prostate size. CONCLUSIONS: Overexpression of PI3K/AKT pathway and BcL-2
      were associated with reduced apoptosis and increased prostate size in BPH.

PMID- 30295141
TI  - Reconceptualizing Self-Affirmation With the Trigger and Channel Framework:
      Lessons From the Health Domain.
AB  - Self-affirmation-a theory-based technique to affirm the adaptive adequacy of the
      self-can promote positive behavior change and adaptive outcomes, although effects
      are variable. We extend a novel framework (Trigger and Channel), proposing three
      conditions that facilitate self-affirmation-induced behavior change: (a) presence
      of psychological threat, (b) presence of resources to foster change, and (c)
      timeliness of the self-affirmation with respect to threat and resources. Using
      health behavior as a focus, we present meta-analytic evidence demonstrating that
      when these conditions are met, self-affirmation acts as a psychological trigger
      into a positive channel of resources that facilitate behavior change. The
      presence of a timely threat and the availability of timely resources
      independently predicted larger self-affirmation effects on behavior change, and
      the two interacted synergistically to predict still larger effects. The results
      illustrate the conditionality of self-affirmation effects and offer guidelines
      for when, where, and for whom self-affirmation will be most effective.

PMID- 30295142
TI  - Characterization of grass carp (Ctenopharyngodon idella) beta-defensin 1:
      implications for its role in inflammation control.
AB  - Considering that fish grows in a complex aquatic environment, there is an
      increasing interest in fish beta-defensins, which is an important group of
      antimicrobial peptides (AMPs). In this study, grass carp (Ctenopharyngodon
      idella) beta-defensin 1 (gcdefb1) was isolated using homology cloning technology.
      Tissue distribution assay showed that gcdefb1 transcripts were expressed with the
      highest levels in brain and liver, followed by some mucous tissues. To examine
      gcDefb1 bioactivities, the recombinant gcDefb1 proteins fused with thioredoxin
      tag protein (Trx) (Trx-Defb1) were induced for production in Escherichia coli
      Rosetta-gami2(DE3)pLysS under optimal expression conditions. The antibacterial
      activity of Trx-Defb1 against Aeromonas hydrophila was assessed and its minimum
      inhibitory concentration (MIC) was 36 MUM. Interestingly, Trx-Defb1 significantly
      inhibited LPS-induced Tnf-alpha (gcTnf-alpha) secretion and nitric oxide
      production in grass carp head kidney monocytes/macrophages (HKM), although Trx
      Defb1 alone had no effect. Our studies provide the first evidence of fish beta
      defensin 1 engaging in both antimicrobial and inflammation suppression process.

PMID- 30295143
TI  - Prognostic Value of White Blood Cells Detected for the First Time After Adjuvant
      Chemotherapy in Primary Operable Non-Small Cell Lung Cancer.
AB  - OBJECTIVE: To investigate the prognostic value of white blood cells detected for
      the first time after adjuvant chemotherapy in primary operable non-small cell
      lung cancer. METHODS: From January 2010 to May 2016, data from 208 patients who
      underwent surgery for non-small cell lung cancer were retrospectively analyzed.
      RESULTS: A white blood cell count detected for the first time after adjuvant
      chemotherapy greater than 7.00 was an independent predictor of poor disease-free
      survival (Hazard ratio: 1.736, 95% confidence interval: 1.267-2.378; P = .001)
      and overall survival (Hazard ratio: 1.802, 95% confidence interval: 1.305-2.471;
      P = .000). In a further study, after myelosuppression, survival analysis
      indicated that the patients with white blood cell counts <2.5 had poorer survival
      than patients with blood cell counts 2.5 to 4.0, P = .031. When the analysis was
      stratified by the type of histology, patients with a white blood cell count >7.00
      and increased white blood cell after chemotherapy compared to pretreatment had a
      poorer prognosis than patients with white blood cell <=7.00 and no increase in
      white blood cell, P = .000 and P = .002, respectively. We further evaluated the
      prognosis of the 2 groups in different levels of white blood cell. In the group
      of patients with white blood cell <=4.0, patients with chemotherapy cycles <=2,
      and >2 showed no differences (Hazard ratio: 2.346, 95% confidence interval: 0.288
      19.073, P = .425). In the group of patients with white blood cell of 4.0 to 7.0,
      the prognosis of patients with chemotherapy cycles <=2 and patients with
      chemotherapy cycles >2 showed no difference (Hazard ratio: 0.560, 95% confidence
      interval: 0.248-1.261, P = .161). In the group of patients with white blood cell
      >7.0, patients with >2 chemotherapy cycles had a better prognosis than patients
      with chemotherapy cycles <=2 (Hazard ratio: 0.573, 95% confidence interval: 0.338
      0.971, P = .037) Conclusions: The level of white blood cells detected for the
      first time after adjuvant chemotherapy is an independent risk factor for non
      small cell lung cancer, especially for patients with nonadenocarcinoma. In
      addition, the level of white blood cells after postoperative adjuvant
      chemotherapy and its change compared with pretreatment might also provide useful
      information regarding the best choice of cycles of adjuvant chemotherapy.

PMID- 30295144
TI  - Long-term dietary supplementation with the green tea cultivar Sunrouge prevents
      age-related cognitive decline in the senescence-accelerated mouse Prone8.
AB  - A majority of the potential health benefits of green tea, including the potential
      to prevent cognitive decline, have been attributed to epigallocatechin gallate
      (EGCG). Sunrouge is a green tea cultivar that contains EGCG and several other
      bioactive components such as quercetin, myricetin, cyanidin and delphinidin. We
      compared the effects of Sunrouge and Yabukita, the most popular Japanese green
      tea cultivar, on cognitive function in the senescence-accelerated mouse Prone8.
      These mice were fed an experimental diet containing Sunrouge extract (SRE) or
      Yabukita extract (YBE). SRE feeding significantly prevented cognitive decline,
      whereas YBE feeding had little effect. Moreover, SRE feeding prevented elevation
      of the amyloid-beta42 level while improving the gene expression of neprilysin and
      decreasing beta-site APP-cleaving enzyme 1 in the brain. These preventive effects
      of SRE against cognitive decline were attributed to the characteristic
      composition of Sunrouge and strongly suggest that consumption of this cultivar
      could protect against age-related cognitive decline.

PMID- 30295146
TI  - Perceptions of body size and health among older queer women of size following
      participation in a health programme.
AB  - Little research examines how older queer (lesbian and bisexual) women understand
      and construct meanings around their body size in the context of individual and
      community norms and identities. Grounded theory was used to analyse transcripts
      from 31 interview participants drawn from a health programme in the San Francisco
      Bay Area. Older queer women of size navigate tensions between body ideals and
      community ideals in and through their experiences of body size. Women's embodied
      experiences of fatness, chronic pain and weight changes shifted in tandem with
      their experience of interactions with other queer women, as well as what bodies
      and body ideals should be in 'the lesbian community'. This study found that
      bodily norms and health ideologies are embedded and embodied in communities and
      navigated through the ongoing formation and configuration of communities over
      time. Body acceptance movements may be out of touch for this population based on
      their internalisation of the medical model in which weight loss automatically
      means improved health. Health interventions for older, queer women of size must
      be community-based to effectively shift behaviours, norms and expectations around
      healthy living in fat, ageing bodies.

PMID- 30295147
TI  - Confidence in accuracy moderates the benefits of retrieval practice.
AB  - The effect of Retrieval Practice refers to the phenomenon that taking a practice
      test is more effective for learning than re-study, probably due to the benefit
      from processes underlying successful retrievals during practice. However, it is
      rarely studied whether other processes (e.g., metacognitive monitoring) during
      retrieval practice may also play an important role. In two experiments, we
      examined whether the effectiveness of retrieval was affected by subjects'
      confidence in their retrieval success. Subjects studied word-pairs and rated
      their confidence after each practice test trial (cued-recall in Exp.1, multiple
      choice in Exp.2), or re-study trial. In both experiments, we observed the classic
      retrieval practice effect. Moreover, in Exp.2, the benefits differed as a
      function of subjects' confidence in their retrieval performance: the effect of
      retrieval practice only emerged for high-confidence trials with higher than 56%
      confidence. In summary, the retrieval practice only facilitates the retention of
      correct answers with high confidence.

PMID- 30295145
TI  - The Noise Exposure Structured Interview (NESI): An Instrument for the
      Comprehensive Estimation of Lifetime Noise Exposure.
AB  - Lifetime noise exposure is generally quantified by self-report. The accuracy of
      retrospective self-report is limited by respondent recall but is also bound to be
      influenced by reporting procedures. Such procedures are of variable quality in
      current measures of lifetime noise exposure, and off-the-shelf instruments are
      not readily available. The Noise Exposure Structured Interview (NESI) represents
      an attempt to draw together some of the stronger elements of existing procedures
      and to provide solutions to their outstanding limitations. Reporting is not
      restricted to prespecified exposure activities and instead encompasses all
      activities that the respondent has experienced as noisy (defined based on sound
      level estimated from vocal effort). Changing exposure habits over time are
      reported by dividing the lifespan into discrete periods in which exposure habits
      were approximately stable, with life milestones used to aid recall. Exposure
      duration, sound level, and use of hearing protection are reported for each life
      period separately. Simple-to-follow methods are provided for the estimation of
      free-field sound level, the sound level emitted by personal listening devices,
      and the attenuation provided by hearing protective equipment. An energy-based
      means of combining the resulting data is supplied, along with a primarily energy
      based method for incorporating firearm-noise exposure. Finally, the NESI
      acknowledges the need of some users to tailor the procedures; this flexibility is
      afforded, and reasonable modifications are described. Competency needs of new
      users are addressed through detailed interview instructions (including
      troubleshooting tips) and a demonstration video. Limited evaluation data are
      available, and future efforts at evaluation are proposed.

PMID- 30295148
TI  - Preparation of gelatin/genipin nanofibrous membrane for tympanic member repair.
AB  - The wound healing for tympanic membrane (TM) perforations is one of the most
      common clinical treatment in otomicrosurgery. Recently, tissue-engineered
      composites and grafts, also new designs of biomaterials are applied to the
      management of TM perforation. In this work, a series of gelatin/genipin
      nanofibrous films were prepared as a patch for repairing TM perforation. Gelatin,
      a type of biomaterial with excellent electrospinning performance, has been used
      for preparing the nanofibers. The genipin, as a crosslinking agent, has been
      blended into the gelatin nanofibers. The reaction between gelatin and genipin
      engender suitable tensile strength and water-resistance for TM patch. The
      survival rate of human umbilical vein endothelial cells and fibroblasts
      demonstrated that the gelatin/genipin nanofiber scaffolds had good
      biocompatibility, which indicated the genipin was a kind of effective and
      nontoxic crosslinking agent for improving the mechanical property and water
      resistance of gelatin films. In short, our work provides a novel macromolecular
      material with good mechanical properties, water-tolerance and excellent
      biocompatibility which could be used as a potential patch for TM repair.

PMID- 30295149
TI  - Interpretation of Optical Coherence Tomography Images for Breast Tissue
      Assessment.
AB  - PURPOSE: Initial studies have shown that optical coherence tomography (OCT) is an
      effective margin-evaluation tool for breast-conserving surgery, but methods for
      the interpretation of breast OCT images have not been directly studied. In this
      work, breast pathologies were assessed with a handheld OCT probe. OCT images and
      corresponding histology were used to develop guidelines for the identification of
      breast tissue features in OCT images. METHODS: Mastectomy and breast-conserving
      surgery specimens from 26 women were imaged with a handheld OCT probe. During
      standard pathology specimen dissection, representative 1-cm * 1-cm tissue regions
      were grossly identified, assessed with OCT, inked for orientation and image
      matching purposes, and processed. Histology slides corresponding to the OCT image
      region were digitally photographed. OCT and histology images from the same region
      were paired by selecting the best structural matches. RESULTS: In total, 2880 OCT
      images were acquired from 26 breast specimens (from 26 patients) and 48 matching
      OCT-histology image pairs were identified. These matched image pairs illustrate
      tissue types including adipose tissue, dense fibrosis, fibroadipose tissue, blood
      vessels, regular and hyperplastic ducts and lobules, cysts, cyst, fibroadenoma,
      invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ,
      calcifications, and biopsy cavities. Differentiation between pathologies was
      achieved by considering feature boundaries, interior appearance, posterior
      shadowing or enhancement, and overall morphologic patterns. CONCLUSIONS: This is
      the first work to systematically catalog the critical features of breast OCT
      images. The results indicate that OCT can be used to identify and distinguish
      between benign and malignant features in human breast tissue.

PMID- 30295150
TI  - Understanding Educational Barriers and Needs of North Korean Defector Nursing
      Students: A Qualitative Descriptive Study.
AB  - INTRODUCTION: A growing number of North Korean defector students enter nursing
      schools in South Korea. Many of them, however, quit nursing school and fail to
      obtain a nurse license. The purpose of this study was to describe the educational
      barriers and needs of North Korean defector nursing students. METHOD: A
      qualitative descriptive approach was employed. Convenience sampling was used, and
      14 students participated. Qualitative content analysis was employed. RESULTS:
      Five themes emerged: lack of preparation for higher education, multiple language
      barriers, differences in education and culture, lack of support and resources,
      and lack of information and understanding. DISCUSSION: South Korean government
      needs to provide North Korean defector students with more practical supportive
      programs. South Korean nursing schools need to provide more transcultural
      education for South Korean students and supportive adaptation programs for North
      Korean defector students to produce culturally competent nurses who provide
      culturally congruent health care.

PMID- 30295152
TI  - The Importance of "Building".

PMID- 30295151
TI  - Introducing NASN's New Evidence-based Clinical Guideline: Students With Seizures
      and Epilepsy.

PMID- 30295153
TI  - Increasing the number of contacts generated during contact tracing interviews.
AB  - To stem the spread of infectious diseases (e.g., Ebola), epidemiologists conduct
      contact tracing interviews (CTIs) with infected individuals regarding their
      contacts who may also be infected. These contact tracing interviews, however, may
      be vulnerable to deadly errors of omission. A promising technique to maximise
      recall is the Cognitive Interview (CI), which is grounded in psychological
      theory. In the present study, participants imagined they were infected with
      meningococcal meningitis and reported their contacts over the previous three days
      during either a control interview or a CI. To model the cognitive impairment
      associated with being sick, half of the participants were interviewed while
      simultaneously completing a cognitive impairment task. The CI generated more
      contacts than the control interview. However, when the cognitive impairment task
      was completed, the CI and the control interview performed similarly. We recommend
      the CI be considered as an alternative to the control interview, particularly if
      the interviewee is not temporarily impaired due to distraction or illness.

PMID- 30295154
TI  - The effect of self-referencing on memory for different kinds of source
      information.
AB  - Self-referential processing has been proven to be effective in improving source
      memory. However, it is unclear whether different types of source information
      would be consistently enhanced when an item is self-referentially processed. In
      two experiments, the authors examined the influence of the self (compared with
      other-referencing and semantic processing) as well as learning intention
      (incidental/intentional learning) on memory for two types of source information
      (spatial location and colour) that differ in the amount of cognitive resources
      they require to be encoded in memory. Results show that self-referencing has
      enhanced memory for spatial location of words whatever this information is
      learned intentionally or incidentally, whereas it cannot facilitate memory for
      the colour of words under the intentional learning condition, nor can it under
      the incidental condition. These findings suggest that self-referential processing
      is beneficial in memory improvement but not all-powerful, a source self-reference
      effect is subject to source information type.

PMID- 30295155
TI  - The effects of episode similarity on children's reports of a repeated event.
AB  - Much research has tested techniques to improve children's reporting of episodes
      from a repeated event by interviewing children after they have experienced
      multiple episodes of a scripted event. However, these studies have not considered
      any effects of the similarity shared between event episodes on children's
      reports. In the current study, 5- to 9-year-olds experienced four episodes of a
      scripted repeated event that shared a high (n = 76) or low (n = 76) degree of
      similarity, and were subsequently interviewed about individual episodes. The
      proportional amount and accuracy of children's reported details were tallied.
      Children reported proportionally more details and more script deviations after
      experiencing the high, compared to low, similarity event. Conversely, children
      were more accurate in their episodic reports when they experienced the low,
      compared to high, similarity event. The current findings have implications for
      the generalisability and comparability of past results across laboratory studies.

PMID- 30295156
TI  - Cortical auditory evoked potentials in cochlear implant listeners via single
      electrode stimulation in relation to speech perception.
AB  - The objectives of this study were to investigate the effects of place of
      stimulation on cortical auditory evoked potentials in relation to speech
      performance in cochlear implant listeners. It was designed that cortical
      responses were recorded for single-electrode bursts at apical, medial and basal
      portions of the electrode array with varying inter-stimulus intervals ranging
      from 300 ms to 5 s. Latency and amplitude of N1 and P2 peaks were analysed in
      relation to monosyllabic word scores. The study sample was 44 adult cochlear
      implant users ranging in age from 28 to 86 years. N1, P2 and N1-P2 amplitudes
      declined significantly from apical to basal electrodes. The most robust and
      pronounced responses were recorded for slower stimulation rates (5 s). Speech
      recognition correlated positively with N1 and N1-P2 amplitudes at the medial
      electrode. P2 latency showed a significant negative correlation with speech
      performance at the apical electrode. At last, cortical responses varied
      significantly depending on the stimulation site and rate. We can objectively
      quantify speech performance with the N1, N1-P2 amplitude and P2 latency in
      cochlear implant users. Deafness-related neural degeneration persists even after
      the cochlear implantation and is more distinct at the base than the apex of the
      cochlea.

PMID- 30295157
TI  - 'One of the good guys': sperm donor masculinity and the falling Danish sperm
      count discourse.
AB  - Sperm banks in Denmark produce and export donor semen worldwide. The role of the
      sperm bank is to provide high-quality, safe semen from desirable donors. However,
      over the last 20 years, global sperm counts are reported to be falling. Along
      with these discourses comes the implication that poor fertility is a personal
      failing, which implies a conflation of 'fertility' with 'potency'. This paper
      draws on qualitative research with Danish sperm donors to explore how donors
      construct their identities as donors and as the producers of 'good sperm'.
      Accounts of the drive to produce the best sperm possible and the resultant
      confidence boost are bound up in ideas about masculine potency and potential and
      bodily performance and set against a backdrop of a moral panic surrounding the
      apparently declining Danish sperm count.

PMID- 30295158
TI  - Regular Mammography Screening Among African American (AA) Women: Qualitative
      Application of the PEN-3 Framework.
AB  - INTRODUCTION: Breast cancer mortality rates among African American (AA) women are
      at 29.2 deaths per 100,000 persons compared with 20.6 deaths per 100,000 persons
      among Caucasian women. Regular mammography screening may significantly reduce
      breast cancer mortality and narrow this disparity. This study guided by PEN-3
      model aims to explore the relationships and expectations domain and identify
      perceptions, enablers, and nurturers of regular mammography among AA women.
      METHOD: As part of an intervention study, in-depth interviews were conducted with
      39 AA women recruited from the emergency department of a public university
      hospital. RESULTS: Women's perceptions included fear and limited knowledge.
      Enablers identified were cost, socioeconomic, and race-related discrimination,
      and health care previous experiences. Nurturers identified included observation
      of family experiences and lack of health-related social support. DISCUSSION:
      Findings underscore the need to develop culturally tailored interventions to
      address the issues salient to this population.

PMID- 30295160
TI  - Endovascular Coil Migration Into the Intestinal Lumen: Two Cases of Successful
      Nonoperative Management.
AB  - Endovascular embolization of visceral arteries is commonly performed as treatment
      for aneurysms, pseudoaneurysms, and emboloradiation of liver tumors; while
      considered relatively safe, it is not without complications. We are reporting 2
      cases of coil migration into the gastrointestinal tract. Patients were
      successfully managed without endoscopic or surgical coil removal. Patients were
      followed after discharge and noted to have no further complications from their
      migrated coils. These cases highlight the success of expectant management for
      coil migration. We recommend against invasive intervention for coil removal as
      first-line treatment for endovascular coil migration into the intestinal tract.
      We urge providers to weigh the risks and benefits of coil removal, prior to
      invasive intervention.

PMID- 30295159
TI  - Assessing the level of institutionalization of donor-funded anti-retroviral
      therapy (ART) programs in health facilities in Uganda: implications for program
      sustainability.
AB  - BACKGROUND: In the context of declining international assistance for ART scale-up
      in Sub-Saharan Africa, the institutionalization of ART programs through
      integrating them in the organizational routines of health facilities is gaining
      importance as a program sustainability strategy. OBJECTIVE: The aims of this
      study were; (i) to compare the level of institutionalization of ART programs in
      health facilities in Uganda and (ii) to explore reasons for variations in the
      degree of program institutionalization. METHODS: In Phase One, we utilized Level
      of Institutionalization Scales developed by Goodman (1993) to measure the degree
      of institutionalization of ART interventions in 195 health facilities across
      Uganda. The 45-item questionnaire measured institutionalization based on four sub
      systems (production, maintenance, supportive, managerial) theorized to make up an
      organization assessed against two levels of institutionalization; routines
      (lowest) niche saturation (highest). In Phase Two, four health facilities were
      purposively selected (2 with the highest and 2 with the lowest
      institutionalization scores) for a multiple case-study involving semi-structured
      interviews with ART clinic managers(n = 32), on-site observations and document
      review. RESULTS: The two highest scoring health facilities had a longer HIV
      intervention implementation history of between 8 and 11 years. The highest
      scoring cases associated intervention institutionalization with sustained
      workforce trainings in ART management, the retention of ART-trained personnel and
      generating in-house ART manuals. The turnover of ART-proficient staff was
      identified as a barrier to intervention institutionalization in the lowest-ranked
      cases. Significant differences in organizational contexts were identified. The
      two highest-ranked health facilities were well-established, higher-tier hospitals
      while the lowest scoring health facilities were lower-level health facilities.
      CONCLUSIONS: The level of institutionalization of ART interventions appeared to
      be differentiated by level of care in the Ugandan health system. Interventions
      aimed at strengthening program institutionalization in lower-level health centers
      at the level of human resources for health could enhance ART scale-up
      sustainability.

PMID- 30295162
TI  - Non-conventional therapeutic technique to replace CRISPR bacteria from biofilm by
      inducible lysogen.
AB  - Bacteriophage can be an effective means of regulating bacterial populations when
      conditions allow phage invasion of bacterial colonies. Phage can either infect
      and lyse a host cell, or insert their DNA into the host cell genome; the latter
      process is called lysogeny. The clustered regularly interspaced short palindromic
      repeat (CRISPR) system, linked with CRISPR-associated (Cas) genes, is a
      regulatory system present in a variety of bacteria which confers immunity against
      bacteriophage. Studies of the group behaviour of bacteria with CRISPR/Cas systems
      have provided evidence that CRISPR in lysogenized bacteria can cause an inability
      to form biofilm. This allows CRISPR-immune bacteria in biofilms to effectively
      resist phage therapy. Our recent work has described a potential therapeutic
      technique to eradicate CRISPR-immune bacteria from a biofilm by a continuous
      influx of lysogens carrying an identical phage sequence. However, this model
      predicted that the CRISPR-immune population could persist for long times before
      eradication. Our current focus is on the use of diverse lysogens against CRISPR
      capable bacterial populations. The goal of this work is to find a suitable
      strategy which can eradicate bacteria with a CRISPR system through the influx of
      finite amounts of distinct lysogens over fixed intervals.

PMID- 30295161
TI  - Do women's perspectives of quality of care during childbirth match with those of
      providers? A qualitative study in Uttar Pradesh, India.
AB  - BACKGROUND: Persistently high maternal mortality levels are a concern in
      developing countries. In India, monetary incentive schemes have increased
      institutional delivery rates appreciably, but have not been equally successful in
      reducing maternal mortality. Maternal outcomes are affected by quality of
      obstetric care and socio-cultural norms. In this light there is need to examine
      the quality of care provided to women delivering in institutions. OBJECTIVE: This
      study aimed to examine pregnant women's expectations of high-quality care in
      public health facilities in Uttar Pradesh, India, and to contrast this with
      provider's perceptions of the same, as well as the barriers that limit their
      ability to provide high-quality care. METHODS: A qualitative descriptive analysis
      was conducted on data from two studies - focus group discussions with rural women
      in their last trimester of pregnancy (conducted in 2014) to understand women's
      experience and satisfaction with maternal care services, and in-depth interviews
      with care providers (conducted in 2016-17) to understand provision of person
      centred care. Provider perspectives were matched with themes of women's
      perspectives on quality of childbirth care in facilities. RESULTS: Major themes
      of care prioritised by women included availability of doctors at the facility;
      availability of medicines; food; ambulance services; maintenance of cleanliness
      and hygiene; privacy; good and safe delivery with no complications; client
      provider interaction; financial cost of care. Many women also voiced no
      expectation of care, indicating disillusionment from the existing system.
      Providers concurred with women on all themes of care except availability of
      doctors, as they felt that trained nurses were proficient in conducting
      deliveries. CONCLUSIONS: This study shows that women have clear expectations of
      quality care from facilities where they go to deliver. Understanding their
      expectations and matching them with providers' perspectives of care is critical
      for efforts to improve the quality of care and thereby impact maternal outcomes.

PMID- 30295163
TI  - The Standard for the Exchange of Nonclinical Data (SEND): Challenges and
      Promises.
AB  - The Standard for the Exchange of Nonclinical Data (SEND) is an implementation of
      the Study Data Tabulation Model for nonclinical studies that enables the U.S.
      Food and Drug Administration (FDA) to modernize and streamline the review
      process. As a result, patients may benefit from speedier approval of new drugs.
      However, SEND implementation and compliance can be challenging and require
      effective cooperation between pharmaceutical companies and contract research
      organizations. In order to improve Society of Toxicologic Pathology (STP)
      members' awareness about SEND, including the steps, obstacles, and mistakes to
      avoid in its implementation while applying for FDA approval, the Career
      Development and Outreach Committee of the STP sponsored a career development
      lunchtime series panel discussion entitled "The Standard for the Exchange of
      Nonclinical Data (SEND): Challenges and Promise" in conjunction with the STP 37th
      Annual Symposium. The presentations and discussion at this workshop provided
      perspectives of experts including pathologists and information technology
      professionals familiar with the SEND submission process and FDA reviewers. This
      article is designed to provide brief summaries of their talks as well as the
      questions asked during this well-received panel discussion.

PMID- 30295164
TI  - Ultra-low-frequency transcutaneous electric nerve stimulation (ULF-TENS) in
      subjects with craniofacial pain: A retrospective study.
AB  - OBJECTIVE: The aim of the present study was to evaluate the effects of ultra-low
      frequency transcutaneous electrical nerve stimulation (ULF-TENS) on pain and
      electromyographic values in subjects affected by temporomandibular disorders.
      METHODS: A retrospective evaluation of 80 non-consecutive patients (58 women, 22
      men, mean age 35.3 +/- 9.9 years) suffering from pain associated with
      temporomandibular disorders was performed. The sample was treated with ULF-TENS,
      and outcomes were evaluated by anamnestic index, dysfunction index, visual analog
      scale, and surface electromyography of the masticatory muscles. RESULTS: An
      improvement was seen in pain and electromyographic values. The visual analog
      scale showed a mean decrease from 8 to 2; surface electromyographic values in the
      masseter area decreased from 2.7 +/- 0.1 to 1.5 +/- 0.1. CONCLUSION: ULF-TENS
      seems to be effective in reducing pain symptomatology of subjects affected by
      temporomandibular disorders, with a reduction in the surface electromyographic
      activity in the masseter area.

PMID- 30295165
TI  - Developing Hispolon based novel anticancer therapeutics against human (NF
      kappabeta) using in silico approach of modelling, docking and protein dynamics.
AB  - Hispolon is a polyphenolic compound derived from black hoof mushroom (Phellinus
      linteus) or shaggy bracket mushroom (Inonotus hispidus) which induces the
      inhibition of cancer promoting NF-kappabeta complex. To develop more potent lead
      molecules with enhanced anticancer efficiency, mechanism of hispolon mediated
      Nuclear Factor-kappabeta inhibition has been investigated by molecular modelling
      and docking. Ten derivatives of hispolon (DRG1-10) have been developed by
      pharmacophore based design with a view to enhance the anticancer efficacy.
      Hispolon and its derivatives were further screened for different pharmacological
      parameters like binding free energy, drug likeliness, ADME, permeability,
      mutagenicity, toxicity and IC50 to find potent lead molecule. Based on
      pharmacological validation, comparative MD simulations have been performed for
      three lead molecules: hispolon, DRG2 and DRG7 complexed with human NF-kappabeta
      upto 50ns. By analysing different factors like: RMSD, RMSF, Rg, SASA, PCA, Gibb's
      free energy plots DRG2 have more binding efficiency compared to hispolon and
      DRG7. In RMSD plot hispolon bound NF-kappabeta has the most deviation within a
      range between 0.125 to 0.45nm and DRG2 bound complex showed the range between
      0.125 to 0.25nm. The residues of NF-kappabeta responsible for hydrophobic
      interactions with ligand e.g. Met469, Leu522 and Cys533 have lowest fluctuation
      values in DRG2 bound complex. Average Rg fluctuation for DRG2 bound NF-kappabeta
      has been recorded under 2.025nm for most of the simulation time which is much
      less compared to hispolon and DRG7. Gibb's free energy plots also define the
      highest stability of DRG2 bound NF-kappabeta.

PMID- 30295166
TI  - Remote post-conditioning and allopurinol reduce ischemia-reperfusion injury in an
      infra-renal ischemia model.
AB  - BACKGROUND:: The aim of this study was to evaluate the effects of the antioxidant
      allopurinol and ischemic post-conditioning on the deleterious effects of ischemia
      followed by reperfusion (I/R) in a standardized model of ischemia involving infra
      renal aortic occlusion in rats. METHODS:: The animals were randomly divided into
      five groups: (A) animals not subjected to ischemia; (B) animals subjected to 2 h
      of ischemia and reperfusion only once; (C) animals given an allopurinol dose by
      gavage, then subjected to 2 h of ischemia and reperfusion only once; (D) animals
      subjected to 2 h of ischemia and post-conditioning and (E) animals that received
      allopurinol, then subjected to 2 h of ischemia and post-conditioning. The blood
      samples and small intestine segments were harvested for analysis after 3 days.
      RESULTS:: The protective effects of the use of allopurinol and ischemic post
      conditioning were observed by measuring aspartate aminotransferase, alanine
      aminotransferase and lactate levels. The benefits of post-conditioning were
      evident from the total antioxidant capacity and creatinine levels, but these
      could not ascertain any positive effects of allopurinol. The histological
      analysis of mesentery revealed that both methods were effective in minimizing the
      harmful effects of the ischemia and reperfusion process. CONCLUSION:: Individual
      protocols significantly reduced I/R systemic injuries, but no additional
      protection was observed when the two strategies were combined.

PMID- 30295167
TI  - Doses of renin-angiotensin system inhibitors but not beta-blockers predict
      outcome after ST-elevation myocardial infarction.
AB  - OBJECTIVES: In patients with ST-elevation myocardial infarction (STEMI), it is
      not clear whether low-dose renin-angiotensin system inhibitors and beta-blockers
      can result in the same benefits achievable with higher target doses. This
      observational study aims to investigate whether higher doses of angiotensin
      converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARB) and
      beta-blockers can improve outcomes in patients with STEMI. METHODS: We recorded
      daily doses of ACEI, ARB, and beta-blockers in 331 patients with STEMI.
      Echocardiographic studies were performed at baseline and were repeated 6 months
      later. Clinical events, including all-cause death and heart failure, were
      followed for 2 years. RESULTS: Patients receiving high-dose ACEI/ARB had less
      increase in left ventricular end-diastolic volume index (LVEDVI) at 6 months. In
      multivariable linear regression model, ACEI/ARB dose or beta-blocker dose was not
      an independent predictor of increase in LVEDVI at 6 months. Kaplan-Meier survival
      curves showed that doses of ACEI/ARB (p = 0.003) and beta-blockers (p = 0.027)
      were significant predictors of death and heart failure. In multivariable Cox
      regression analysis, independent predictors of all-cause death and heart failure
      were diabetes mellitus (p = 0.001), left ventricular ejection fraction (p =
      0.026), and ACEI/ARB dose (p = 0.025). Beta-blockers dose was not a predictor of
      clinical events in multivariable analysis (p = 0.413). CONCLUSION: High-dose
      ACEI/ARB, but not beta-blocker, was associated with lower rate of all-cause death
      and heart failure in patients with STEMI.

PMID- 30295168
TI  - Total contact casting versus traditional dressing in diabetic foot ulcers.
AB  - This study compared the treatment of total contact casting (TCC) with traditional
      dressing treatment (TD) in the management of neuropathic diabetic plantar ulcers.
      Thirty-one patients with plantar ulcers without any gross infection,
      osteomyelitis or gangrene were randomly assigned to the TCC group (n = 15) or TD
      group (n = 16). In the experimental group, TCC was applied on the initial visit
      and subjects were instructed to limit ambulation to one-third of their usual
      activity. Subjects in the control group (TD) were prescribed dressing changes and
      were advised against bearing weight on the involved extremity. Ulcers were
      considered healed if they showed complete skin closure with no drainage. Ulcers
      were considered not healed if they showed no decrease in size by 6 weeks or if
      infection developed requiring hospitalization. In the TCC group, 12 of 15 ulcers
      healed in 48 +/- 7 days; in the TD group, 10 of 16 ulcers healed in 58 +/- 9
      days. Comparatively higher rate of ulcer healing with fewer infections was seen
      in the TCC group. We conclude TCC is a more effective method than dressing for
      treating diabetic plantar ulcers reducing the risks of amputation.

PMID- 30295169
TI  - A Brief Introduction to Antibody-Drug Conjugates for Toxicologic Pathologists.
AB  - Antibody-drug conjugates (ADCs) are an emerging class of anticancer therapeutics,
      delivering highly cytotoxic molecules directly to cancer cells. ADCs are composed
      of an antibody, a small molecule drug, and a linker attaching one to another.
      Antibodies are directed to a large variety of antigens overexpressed on tumor
      cells, tumor vasculature, or tumor-supporting stroma. After internalization, the
      ADC is transferred to lysosomes where the cytotoxic component is released,
      finally killing the target cell. All ADCs are administered via intravenous
      injection. Once in the circulation, linker stability in plasma is of high
      importance. In vivo studies in animals address the release of payload over time
      and typically measure total antibody, conjugated ADC, and free drug. ADC
      development is driven by ICH (International Council for Harmonisation) guidelines
      S6(R1) and S9. Dose-limiting toxicities of current ADCs are mainly associated
      with the payload and correlate well between clinical trials and nonclinical
      studies in rodents and nonrodents. This mini review is intended to provide
      general information about ADCs in oncology and shall assist the toxicologic
      pathologist in correctly interpreting morphological findings acquired in toxicity
      studies with this entity.

PMID- 30295170
TI  - Psychosocial and Behavioral Correlates of A1C and Quality of Life Among Young
      Adults With Diabetes.
AB  - PURPOSE: The purpose of this study was to evaluate relationships between
      behavioral and psychosocial constructs, A1C, and diabetes-dependent quality of
      life (DQoL) among low-socioeconomic status, ethnically diverse young adults with
      diabetes. METHODS: Using baseline data of 81 participants in the Resilient,
      Empowered, Active Living (REAL) randomized controlled trial, behavioral,
      cognitive, affective, and experiential variables were correlated with A1C and
      DQoL while adjusting for demographic characteristics, and these relationships
      were examined for potential effect modification. RESULTS: The data indicate that
      depressive symptoms and satisfaction with daily activities are associated with
      both A1C and DQoL, while diabetes knowledge and participation in daily activities
      are associated with neither A1C nor DQoL. Two constructs, diabetes distress and
      life satisfaction, were associated with DQoL and were unrelated to A1C, while 2
      constructs, self-monitoring of blood glucose and medication adherence, were
      associated with A1C but unrelated to DQoL. These relationships were largely
      unchanged by adjusting for demographic characteristics, while numerous effect
      modifications were found. CONCLUSION: The data suggest that when tailoring
      interventions, depressive symptoms and satisfaction with daily activities may be
      particularly fruitful intervention targets, as they represent modifiable risk
      factors that are associated with both A1C and DQoL.

PMID- 30295171
TI  - Prevalence and determinants of pre-lacteal feeding in South Sudan: a community
      based survey.
AB  - BACKGROUND: Pre-lacteal feeding (PLF) is a barrier to optimal breastfeeding and
      increases the risk of diarrhoea and acute respiratory tract infections in
      infants.The prevalence and predictors of PLF are not well studied in South Sudan.
      Understanding the predictors of PLF is crucial in designing interventions to
      increase exclusive breastfeeding (EBF) rates. OBJECTIVE: To assess the prevalence
      and factors associated with PLF in Jubek State, South Sudan. METHOD: This was a
      community based cross-sectional study of 810 mothers of children under two years
      of age in Jubek State, South Sudan. Mothers were interviewed in their homes using
      a semi-structured questionnaire to collect data on PLF, socio-demographic and
      birth characteristics. Multivariable analysis was used to identify factors
      independently associated with PLF. RESULTS: A total of 426/810 (53 %), 95%
      confidence interval (CI) [48 %, 59 %] mothers had given pre-lacteal feeds to
      their infants. The commonest pre-lacteal feeds included glucose solution (54%),
      water (26%), and infant formula (14%). Having received antenatal breastfeeding
      counselling decreased the odds of PLF [adjusted odds ratio (AOR) 0.60; 95% CI
      (0.43, 0.82)]; while discarding of colostrum increased the use of pre-lacteal
      feeds [AOR 1.57; 95% CI (1.17, 2.11)]. CONCLUSION: The prevalence of PLF in South
      Sudan is high. Predictors of PLF included lack of breastfeeding counselling and
      discarding of colostrum. Infant feeding counselling should be given to all
      pregnant women in the health facilities and communities. The counselling should
      emphasize the health benefits of colostrum and discourage the practice of
      discarding it.

PMID- 30295172
TI  - Critical Appraisal of the Treatment Planning Performance of Volumetric Modulated
      Arc Therapy by Means of a Dual Layer Stacked Multileaf Collimator for Head and
      Neck, Breast, and Prostate.
AB  - PURPOSE: To ascertain whether a new delivery system (the Halcyon system) equipped
      with dual-layer stacked multileaf collimator operating in a mode, which allows
      independent, fully interdigitating motion of both layers and 6 flattening filter
      free energy, could generate plans of high clinical quality compared to a well
      established delivery system with single layer multileaf collimator. METHODS:
      Twenty patients in each of the 3 groups (advanced head and neck, breast, and high
      risk prostate) were selected for an in silico planning study. For each patient,
      reference plans were developed for volumetric modulated arc therapy technique
      with 6 MV photon beams from a TrueBeam linear accelerator and compared against
      the corresponding plans for the Halcyon system. Plan comparison was performed in
      terms of dose volume histogram quantitative analysis. RESULTS: Concerning the
      planning target volumes, with identical dose calculation and optimization
      algorithms and with identical planning techniques, no clinically relevant
      difference in coverage (D98%), hot spot (D2%), or homogeneity was observed.
      Similarly, for all the organs at risk, the dosimetric findings showed that (1)
      all planning constraints were met by the 2 delivery systems and (2) although
      statistical significant differences were reported for most of the parameters but
      none of these were judged of potential clinical relevance. CONCLUSION: The data
      presented confirmed that the new delivery system can generate treatment plans for
      volumetric modulated arc therapy with the same dosimetric quality of what is
      achievable with other systems routinely used in the clinics without significantly
      changing the current practice. Additional studies which customize the
      optimization parameters for each delivery device would complement the spectrum of
      investigations.

PMID- 30295173
TI  - Continuing Education Course #3: Toxicologic Pathology of the Peripheral Nervous
      System (PNS): Overview, Challenges, and Current Practices.
AB  - Peripheral nervous system (PNS) toxicity is a frequent adverse effect encountered
      in patients treated with certain therapeutics (e.g., antiretroviral drugs, cancer
      chemotherapeutics), in occupational workers exposed to industrial chemicals
      (e.g., solvents), or during accidental exposures to household chemicals and/or
      environmental agents (e.g., pesticides). However, the literature and expertise
      needed for the effective design, conduct, analysis, and reporting of safety
      studies to identify and define PNS toxicity are hard to find. This half-day
      course familiarized participants with basic PNS biology; causes and mechanisms of
      PNS pathology; classic methods and current best practice recommendations for PNS
      sampling, preparation, and evaluation; and examples of commonly observed lesions
      and artifacts. Three concluding case presentations synthesized information from
      the prior technical lectures by presenting real-world examples of lesions caused
      by drugs and chemicals to demonstrate how PNS toxicity may be addressed in
      evaluating product safety during nonclinical studies. Topics emphasized
      comparative and correlative data among animal species used in toxicity studies
      and clinical evaluation in humans in order to facilitate the translation of
      animal data into human risk assessment with respect to PNS toxicologic pathology.

PMID- 30295174
TI  - Acute chest syndrome in sickle cell anaemia: higher serum levels of interleukin-8
      and highly sensitive C-reactive proteins are associated with impaired lung
      function.
AB  - BACKGROUND: Sickle cell anaemia (SCA) is a chronic inflammatory disorder with
      multiple organ manifestations including acute and long-term pulmonary
      dysfunction. AIMS/OBJECTIVES: To assess lung function of children with SCA and
      determine the possible role of acute chest syndrome (ACS), serum inflammatory
      cytokines, highly sensitive C-reactive protein (hs-CRP), leucocytes and 25
      hydroxyvitamin D on the development of impaired lung function. SUBJECTS AND
      METHODS: Lung function of 76 children with SCA was determined by spirometer and
      classified into normal or impaired. Sociodemographic, clinical, haematological,
      biochemical and immunological data of the two groups were compared by univariate
      and multivariate analyses. RESULTS: Fifty (65.8%) patients had impaired lung
      function, comprising of 30.3%, 3.9% and 31.6% with restrictive, obstructive and
      mixed disease patterns, respectively. Children with previous ACS were 3.6 times
      more likely to have impaired lung function than those without ACS (82.1% vs
      56.3%, p = 0.02, OR 3.6, 95% CI 1.2-10.8). Interleukin (IL)-8 and hs-CRP were
      significantly higher in patients with impaired lung function (p = 0.02 and
      <0.001, respectively). Using logistic regression, previous ACS (OR 5.8, 95% CI
      1.1-5.8, p = 0.03) and higher serum IL-8 levels (OR 3.0, 95% CI 1.0-8.0, p =
      0.02) independently predicted the presence of abnormal lung function.
      CONCLUSIONS: Lung dysfunction, predominantly restrictive pattern, is common in
      SCA and is associated with previous ACS and alterations in immunological markers,
      especially serum IL-8 and hs-CRP. ABBREVIATIONS: ACS: acute chest syndrome; CBT:
      chronic blood transfusion; ELISA: enzyme-linked immunosorbent assay; FEV1: forced
      expiratory volume in 1 s; FVC: forced vital capacity; HPLC: high-density liquid
      chromatography; hs-CRP: highly sensitive C-reactive proteins; HU: hydroxyurea;
      IL: Interleukin; PEFR: peak expiratory flow rate; SEM: standard error of the
      mean; TLC: total lung capacity; 25-OHD: 25-hydroxyvitamin D; VOC: vaso-occlusive
      crisis; WGH: Wesley Guild Hospital.

PMID- 30295175
TI  - Considerations for Preclinical Safety Assessment of Adeno-Associated Virus Gene
      Therapy Products.
AB  - Progress in understanding the molecular bases of human health and disease in
      recent decades has flourished making it possible for the field of gene therapy
      (GT) to offer new possibilities for treating, and even curing, a plethora of
      medical conditions such as monogenic disorders and metabolic diseases. GT is a
      therapeutic intervention to genetically alter or modify living cells by means of
      gene delivery achieved using either viral vectors or nonviral vectors, with adeno
      associated virus (AAV) vectors constituting market-share majority. Although GT is
      conceptually attractive, adverse and even fatal iatrogenic complications have
      marred the initial enthusiasm of clinical successes. The properties of
      investigational AAV-based GT may pose safety concerns unique from those of small
      molecule drugs and other macromolecular biologics, such as ectopic or unregulated
      expression of the transgene, long-term persistence, and off-target distribution.
      Herein, we discuss considerations in the design of a comprehensive preclinical
      safety program for AAV-based GT prior to administration in humans.

PMID- 30295176
TI  - A meta-analysis of techniques to promote motivation for health behaviour change
      from a self-determination theory perspective.
AB  - A systematic review and meta-analysis was conducted of the techniques used to
      promote psychological need satisfaction and motivation within health
      interventions based on self-determination theory (SDT; Ryan & Deci, 2017. Self
      determination theory: Basic psychological needs in motivation, development, and
      wellness. New York, NY: Guilford Press). Eight databases were searched from 1970
      to 2017. Studies including a control group and reporting pre- and post
      intervention ratings of SDT-related psychosocial mediators (namely perceived
      autonomy support, need satisfaction and motivation) with children or adults were
      included. Risk of bias was assessed using items from the Cochrane risk of bias
      tool. 2496 articles were identified of which 74 met inclusion criteria; 80% were
      RCTs or cluster RCTs. Techniques to promote need supportive environments were
      coded according to two established taxonomies (BCTv1 and MIT), and 21 SDT
      specific techniques, and grouped into 18 SDT based strategies. Weighted mean
      effect sizes were computed using a random effects model; perceived autonomy
      support g = 0.84, autonomy g = 0.81, competence g = 0.63, relatedness g = 0.28,
      and motivation g = 0.41. One-to-one interventions resulted in greater competence
      satisfaction than group-based (g = 0.96 vs. 0.28), and competence satisfaction
      was greater for adults (g = 0.95) than children (g = 0.11). Meta-regression
      analysis showed that individual strategies had limited independent impact on
      outcomes, endorsing the suggestion that a need supportive environment requires
      the combination of multiple co-acting techniques.

PMID- 30295177
TI  - Nematode parasites in young cattle: what role for unexpected species?
AB  - AIMS To investigate the timing of infection of beef calves with sheep nematode
      species on three sheep and beef farms, and to determine the prevalence of cross
      infection in calves before weaning across a larger number of farms. METHODS Farms
      in the Far North, Gisborne and Tararua districts, in the North Island of New
      Zealand, were enrolled in 2014. Fresh faecal samples were collected from
      approximately 10 calves on each farm between birth and up to 5 months after
      weaning. In 2016, faecal samples were collected from calves before weaning from
      22 farms across the upper North Island. For both trials faecal samples were
      assessed for faecal nematode egg counts and cultured to determine parasite genus.
      For samples from the three farms, larvae were identified to species using a
      multiplex PCR assay. RESULTS On the three farms, the median percentage of sheep
      nematode species detected in faecal cultures was 25 (min 3, max 77)%. The main
      sheep species detected were Cooperia curticei and Haemonchus spp. (putatively
      contortus). In faecal samples collected before weaning from 22 farms, Haemonchus
      spp. were present in 19/22 samples, and the median prevalence was 15 (min 0, max
      73)% of the total larvae cultured. CONCLUSIONS AND CLINICAL RELEVANCE The
      implications of sheep nematode species being present in calves should be
      considered by farmers and veterinarians when undertaking anthelmintic efficacy
      testing, as they may contribute to false conclusions regarding anthelmintic
      efficacy. Pre-weaning calves may also be a possible source of contamination
      and/or refugia for Haemonchus spp. on farms and should be considered when
      developing parasite control plans for sheep.

PMID- 30295178
TI  - Have Alcohol Management Plans Reduced Violence Against Women in Cape York,
      Australia?
AB  - In 2002/2003, the Queensland Government released a decision that Alcohol
      Management Plans (AMPs) were to be introduced to most Indigenous communities in
      Cape York, Australia, in an effort to address violence generally and specifically
      violence against women and children. By 2008, increased restrictions brought
      total prohibition in some communities and tightened restrictions in others. This
      project provides a pre-/postprohibition comparison and analysis of injuries,
      injuries that involved alcohol and verified police reported assaults. Supporting
      this are rich community survey data which together aim to elicit the effect
      restricting alcohol had on violent activity in the communities, particularly for
      women.

PMID- 30295179
TI  - If It Wasn't Rape, Was It Sexual Assault? Comparing Rape and Sexual Assault
      Acknowledgment in College Women Who Have Experienced Rape.
AB  - The present study investigated (a) comparisons in rates of rape and sexual
      assault acknowledgment and (b) a comprehensive multivariate multinomial logistic
      model predicting rape and sexual assault acknowledgment in a sample of 174
      college women who had experienced rape. Significantly more women acknowledged
      having experienced sexual assault than rape. Greater perceived perpetrator force
      was associated with increased likelihood of rape and sexual assault
      acknowledgment. Increased age and greater perceived emotional impact were
      associated with increased odds of rape acknowledgment. Implications for policy,
      education, and practice within university settings are discussed.

PMID- 30295180
TI  - "I Was Grabbed by My Pussy and Its #NotOkay": A Twitter Backlash Against Donald
      Trump's Degrading Commentary.
AB  - The present study assessed how individuals used the #NotOkay hashtag on Twitter
      to respond to Donald Trump's comments about grabbing women by their genitals. We
      analyzed 652 tweets which included commentary about the hashtag. Three main
      themes emerged: (a) users' acknowledgment and condemnation of rape culture, (b)
      Donald Trump and the national state of sexual assault, and (c) engaging men and
      boys to end violence against women. Our findings emphasize that powerful
      political leaders can be salient symbols of rape culture, and Twitter is used as
      a public platform to organize and challenge problematic social discourse and call
      for action/change.

PMID- 30295181
TI  - Cubilin, the intrinsic factor-vitamin B12 receptor in development and disease.
AB  - Gp280/Intrinsic factor-vitamin B12 receptor/Cubilin (CUBN) is a large endocytic
      receptor serving multiple functions in vitamin B12 homeostasis, renal
      reabsorption of protein or toxic substances including albumin, vitamin D-binding
      protein or cadmium.Cubilin is a peripheral membrane protein consisting of 8
      epidermal growth factor (EGF)-like repeats and 27 CUB (defined as Complement
      C1r/C1s, Uegf, BMP1) domains. This structurally unique protein interacts with at
      least two molecular partners, amnionless (AMN) and Lrp2/Megalin. AMN is involved
      in appropriate plasma membrane transport of Cubilin whereas Lrp2 is essential for
      efficient internalization of Cubilin and its ligands. Observations gleaned from
      animal models with Cubn deficiency or human diseases demonstrate the importance
      of this protein. In this review addressed to basic research and medical
      scientists we summarize currently available data on Cubilin and its implication
      in renal and intestinal biology. We also discuss the role of Cubilin as a
      modulator of Fgf8 signaling during embryonic development and propose that the
      Cubilin-Fgf8 interaction may be relevant in human pathology, including in cancer
      progression, heart or neural tube defects. We finally provide experimental
      elements suggesting that some aspects of Cubilin physiology might be relevant in
      drug design.

PMID- 30295182
TI  - Antimicrobial Capacity of Plant Polyphenols against Gram-positive Bacteria: a
      Comprehensive Review.
AB  - BACKGROUND: Multi-drug-resistant bacteria such as Methicillin-resistant
      Staphylococcus aureus (MRSA) disseminate rapidly amongst patients in healthcare
      facilities and suppose an increasingly important cause of community-associated
      infections and associated mortality. The development of effective therapeutic
      options against resistant bacteria is a public health priority. Plant polyphenols
      are structurally diverse compounds that have been used for centuries for
      medicinal purposes, including infections treatment. Based on the existing
      evidence on the polyphenols' antibacterial capacity, polyphenols may be
      postulated as an alternative or complementary therapy for infectious diseases.
      OBJECTIVE: Review the antimicrobial activity of plant polyphenols against Gram
      positive bacteria, especially against S. aureus and its resistant strains.
      Determine the main bacterial molecular targets of polyphenols and their potential
      mechanism of action. METHODOLOGY: The most relevant reports on plant polyphenols'
      antibacterial activity and their putative molecular targets were studied. We also
      performed virtual screening of thousand different polyphenols against proteins
      involved in the peptidoglycan biosynthesis to find potential valuable bioactive
      compounds. RESULTS: Several polyphenols: phenolic acids, flavonoids (especially
      flavonols), tannins, lignans, stilbenes and combinations of these in botanical
      mixtures, have exhibited significant antibacterial activity against resistant and
      non-resistant Gram-positive bacteria at low ug/mL range MIC values. Their
      mechanism of action is quite diverse, targeting cell wall, lipid membrane,
      membrane receptors and ion channels, bacteria metabolites, and biofilm formation.
      Synergic effects were also demonstrated for some combinations of polyphenols and
      antibiotics. CONCLUSION: Plant polyphenols mean a promising source of
      antibacterial agents, either alone or in combination with existing antibiotics,
      for the development of new antibiotic therapies.

PMID- 30295183
TI  - Aptamer Based Targeted Drug Delivery Systems: Current Potential and Challenges.
AB  - Aptamers are single-stranded DNA or RNA with 20-100 nucleotides in length that
      can specifically bind to target molecules via formed three-dimensional
      structures. These innovative targeting molecules have attracted an increasing
      interest in biomedical field. Compared to traditional protein antibodies,
      aptamers have several advantages, such as small size, high binding affinity,
      specificity, good biocompatibility, high stability and low immunogenicity, which
      all contribute to their wide application in biomedical field. Aptamers can bind
      to the receptors on the cell membrane and mediate themselves or conjugated
      nanoparticles to enter into cells. Therefore, aptamers can be served as ideal
      targeting ligands for drug delivery. Since their excellent properties, different
      aptamer-mediated drug delivery systems had been developed for cancer therapy.
      This review provides a brief overview of recent advances in drug delivery systems
      based on aptamers. The advantages, challenges and future prospectives are also
      discussed.

PMID- 30295184
TI  - Phenylboronic acid-polymers for biomedical applications.
AB  - BACKGROUND: Phenylboronic acid-polymers (PBA-polymers) have attracted tremendous
      attention as potential stimuli-responsive materials with applications in drug
      delivery depots, scaffolds for tissue engineering, HIV barriers, and biomolecule
      detecting/sensing platforms. The unique aspect for PBA-polymers is their
      interactions with diols, which results in reversible, covalent bond formations.
      This very nature of reversible bonding between boronic acids and diols has been
      fundamental to their applications in the biomedical area. METHODS: We have
      searched peer-reviewed articles including reviews from Scopus, PubMed, and Google
      Scholar with a focus on the 1) chemistry of PBA, 2) synthesis of PBA-polymers,
      and 3) their biomedical applications. RESULTS: We have summarized approximately
      179 papers in this review. Most of the applications described in this review are
      focused on the unique ability of PBA molecules to interact with diol molecules
      and the dynamic nature of the resulting boronate esters. The strong sensitivity
      of boronate ester groups towards the surrounding pH also makes these molecules
      stimuli responsive. In addition, we also discuss how the re-arrangement of the
      dynamic boronate ester bonds render PBA-based materials with other unique
      features such as self-healing and shear thinning. CONCLUSION: The presence of PBA
      in polymer chain can render it with diverse functions/relativities without
      changing their intrinsic properties. In this review, we discuss the development
      of PBA polymers with diverse functions and their biomedical applications with a
      specific focus on the dynamic nature of boronate ester groups.  .

PMID- 30295185
TI  - Metabolomics of exhaled breath condensate by nuclear magnetic resonance
      spectroscopy and mass spectrometry: a methodological approach.
AB  - Respiratory diseases present a very high prevalence in the general population,
      with an increase in morbidity, mortality and health-care expenses worldwide. They
      are complex and heterogeneous pathologies that may present different pathological
      facets in different subjects, often with personal evolution. Therefore, there is
      a need to identify patients with similar characteristics, prognosis or treatment,
      defining the so-called phenotype, but also to mark specific differences within
      each phenotype, defining the endotypes. Biomarkers are very useful to study
      respiratory phenotypes and endotypes. Metabolomics, one of the recently
      introduced "omics", is becoming a leading technique for biomarker discovery. For
      the airways, metabolomics appears to be well suited as the respiratory tract
      offers a natural matrix, the exhaled breath condensate (EBC), in which several
      biomarkers can be measured. In this review, we will discuss the main
      methodological issues related to the application of nuclear magnetic resonance
      (NMR) spectroscopy and mass spectrometry (MS) to EBC metabolomics for
      investigating respiratory diseases.

PMID- 30295186
TI  - Novel technologies for dipeptide drugs design and their implantation.
AB  - The article is an overview of author's data obtained in the framework of the
      project "The Creation of dipeptide preparations" at the V.V. Zakusov Institute of
      Pharmacology, Moscow, Russia. Advantages of dipeptides over longer peptides
      consist in that they are orally active owing to higher stability and ability to
      penetrate biological barriers due to presence of specific ATP-dependent
      transporters in enterocytes and blood-brain barrier. Two original approaches for
      dipeptide drugs design have been developed. Both of them are based on the idea of
      a leading role of central dipeptide fragment of the peptide chain beta-turn in
      the peptide-receptor interaction. The first approach, named "peptide drug-based
      design" represents the transformation of known nonpeptide drug into its dipeptide
      topological analog. The latter usually corresponds to a beta-turn of some
      regulatory peptide. The second approach represents the design of tripeptoide
      mimetic of the beta-turn of regulatory peptide or protein. The results of the
      studies, which led to the discovery of endogenous prototypes of the known non
      peptide drugs piracetam and sulpiride, are presented herein. The paper discusses
      the process, based on the above-mentioned principles, that was used in designing
      of nontoxic, orally available, highly effective dipeptide drugs: nootropic
      noopept, dipeptide analog of piracetam; antipsychotic dilept, neurotensin
      tripeptoid analog; selective anxiolytic GB-115, tripeptoid analog of CCK-4, and
      potential neuroprotector GK-2, homodimeric dipeptide analog of NGF.

PMID- 30295187
TI  - Is very low LDL-C harmful?
AB  - BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is a major cardiovascular
      (CV) risk factor. Accumulating evidence supports a linear association between LDL
      C levels and CV risk. However, the lower limit of LDL-C that might offer CV
      benefits without any safety concerns is still a topic of debate. OBJECTIVE: The
      purpose of this review is to present the safety of reducing LDL-C to low levels
      as it comes from major lipid-lowering drug studies, and to discuss data on
      several safety events that have been associated with low LDL-C levels. METHODS: A
      comprehensive literature search was performed to identify available data from
      clinical studies evaluating the association of low LDL-C with safety outcomes.
      RESULTS: Several large trials have evaluated the safety or reducing LDL-C to
      levels lower than 50 mg/dl or even lower than 25 mg/dl, more commonly with the
      use of combination of statins with ezetimibe or proprotein convertase subtilisin
      kexin 9 inhibitors. In almost all trials, CV benefits were observed with LDL-C
      levels of 50 mg/dl or less compared with higher levels. In terms of safety,
      reduction of LDL-C to such levels was not associated with any significant adverse
      event. Of importance, cancer and hemorrhagic stroke incidences were not increased
      in patients attaining LDL-C lower than 40-50 mg/dl. Data regarding the impact of
      lowering LDL-C with neurocognitive disorders are contradictory; nevertheless,
      most studies stand in favor of neurocognitive safety with LDL-C reductions to low
      levels. CONCLUSION: Achieving an LDL-C of 40-50 mg/dl seems to be safe, and
      importantly might offer CV beneficial effects. Data for attaining levels below 25
      mg/dl is limited, however in favor of such reductions.

PMID- 30295188
TI  - Identification and characterization of genes in curcuminoid pathway of Curcuma
      zedoaria Roscoe.
AB  - BACKGROUND: Curcuminoid genes have an important role in the biosynthesis of
      curcumin, a valuable bioactive compound, in Curcuma species. However, there have
      not been any reports of these genes in Curcuma zedoaria. OBJECTIVE: The present
      work reports on the isolation of genes encoding enzymes in curcuminoid metabolic
      pathway and their expression in C. zedoaria. METHOD: The primers were designed
      from untranslation regions of DCS, CURS1, CURS2 and CURS3 genes which involve in
      curcuminoid biosynthesis in C. longa to isolate the corresponding full-length
      genes in C. zedoaria. RT-PCR amplification and HPLC analysis used to estimate
      expression of genes and biosynthesis of curcumin in both rhizome and callus.
      RESULTS: The results showed that all four genes from C. zedoaria (named CzDCS,
      CzCURS1, CzCURS2 and CzCURS3) and C. longa have a high identity (approximately
      99%) and lengths of genes from C. zedoaria are 1382, 1240, 1288 and 1265 nu,
      respectively. CzCURS1, 2 and 3 genes have one intron while CzDCS has two introns.
      RT -PCR amplification indicated curcuminoid genes have expressed mRNA in rhizome
      and callus of C. zedoaria. Curcumin, a major component of curcuminoids, was also
      found in callus by HPLC analysis. CONCLUSION: The sequence information of DCS and
      CURS1-3 genes in C. zedoaria will be very valuable for subsequent study on the
      effects of elicitors on the transcription of genes involving in curcuminoid
      biosynthesis pathway.

PMID- 30295189
TI  - EZH2 RIP-seq Identifies Tissue-specific Long Non-coding RNAs.
AB  - BACKGROUND: Polycomb Repressive Complex 2 (PRC2) catalyzes histone methylation at
      H3 Lys27, and plays crucial roles during development and diseases in numerous
      systems. Its catalytic subunit EZH2 represents a key nuclear target for long non
      coding RNAs (lncRNAs) that emerging to be a novel class of epigenetic regulator
      and participate in diverse cellular processes. LncRNAs are characterized by high
      tissue-specificity; however, little is known about the tissue profile of the EZH2
      interacting lncRNAs. OBJECTIVE: Here we performed a global screening for EZH2
      binding lncRNAs in tissues including brain, lung, heart, liver, kidney,
      intestine, spleen, testis, muscle and blood by combining RNA immuno-
      precipitation and RNA sequencing. We identified 1328 EZH2-binding lncRNAs, among
      which 470 were shared in at least two tissues while 858 were only detected in
      single tissue. An RNA motif with specific secondary structure was identified in a
      number of lncRNAs, albeit not in all EZH2-binding lncRNAs. The EZH2-binding
      lncRNAs fell into four categories including intergenic lncRNA, antisense lncRNA,
      intron-related lncRNA and promoter-related lncRNA, suggesting diverse regulations
      of both cis and trans-mechanisms. A promoter-related lncRNA Hnf1aos1 bound to
      EZH2 specifically in the liver, a feature same as its paired coding gene Hnf1a,
      further confirming the validity of our study. In addition to the well known EZH2
      binding lncRNAs like Kcnq1ot1, Gas5, Meg3, Hotair and Malat1, majority of the
      lncRNAs were firstly reported to be associated with EZH2. CONCLUSION: Our
      findings provide a profiling view of the EZH2-interacting lncRNAs across
      different tissues, and suggest critical roles of lncRNAs during cell
      differentiation and maturation.

PMID- 30295190
TI  - Utilization of Analytical Omics Tools in the Molecular Diagnostics of Multiple
      Myeloma.
AB  - Multiple myeloma (MM) is characterized by the clonal proliferation of malignant
      plasma B-lymphocytes and even as of today, it is an incurable disease. MM
      accounts for approximately 10% of all hematologic cancers. Its molecular
      pathogenesis is poorly understood, but the bone marrow microenvironment of tumor
      cells and genetic factors have apparent roles in the process. Accurate diagnosis
      is important to properly identify and stratify the disease, however, MM
      identification steps are time-consuming and expensive. Thus, development of early
      molecular diagnostic methods is of high importance in order to start proper
      therapies as early in the disease progression as possible, given the nature of
      the poor survival rates/remission periods. Molecular diagnostics via analytical
      omics represents one of the promising toolsets to speed up the diagnostic
      process. In this paper, we critically review the utilization of state of the art,
      high sensitivity analytical omics approaches (genomics, proteomics, metabolomics,
      lipidomics and glycomics) in MM diagnostics at the molecular level.

PMID- 30295191
TI  - Synthesis, 2D-QSAR studies and Biological Evaluation of Quinazoline Derivatives
      as potent Anti-Trypanosoma cruzi Agents.
AB  - BACKGROUND: Chagas disease affects about 7 million people worldwide. Only two
      drugs are currently available for the treatment for this parasite disease,
      namely, benznidazol (Bzn) and nifurtimox (Nfx). Both drugs have limited curative
      power in the chronic phase of the disease. Therefore, continuous research is an
      urgent need so as to discover novel therapeutic alternatives. OBJECTIVE: The
      development of safer and more efficient therapeutic anti-T. cruzi drugs continues
      to be a major goal in trypanocidal chemotherapy. METHOD: Synthesis, 2D-QSAR and
      drug-like physicochemical properties of a set of quinazolinone and quinazoline
      derivatives were studied as trypanocidal agents. All compounds were screened in
      vitro against Trypanosoma cruzi (Tulahuen strain, Tul 2 stock) epimastigotes and
      bloodstream trypomastigotes. RESULTS: Out of 34 compounds synthesized and tested,
      six compounds (5a, 5b, 9b, 9h, 13f and 13p) displayed significant activity
      against both epimastigotes and tripomastigotes, without exerting toxicity on Vero
      cells. CONCLUSION: The antiprotozoal activity of these quinazolinone and
      quinazoline derivatives represents an interesting starting point for a medicinal
      chemistry program aiming at the development of novel chemotherapies for Chagas
      disease.

PMID- 30295192
TI  - Phenolic Imidazole Derivatives with Dual Antioxidant/Antifungal Activity:
      Synthesis and Structure-Activity Relationship.
AB  - BACKGROUND: Previous publications show that the addition of a phenolic
      antioxidant to an antifungal agent, considerably enhances the antifungal
      activity. OBJECTIVE: Synthesis of novel compounds combining phenolic units with
      linear or cyclic nitrogen-containing organic molecules with
      antioxidant/antifungal activity using methodologies previously developed in the
      group. METHODS: Several N-[1,2-dicyano-2-(arylidenamino)vinyl]-O
      alkylformamidoximes 3 were synthesized and cyclized to 4,5-dicyano-N-(N'
      alcoxyformimidoyl)-2-arylimidazoles 4 upon reflux in DMF, in the presence of
      manganese dioxide or to 6-cyano-8-arylpurines 5 when the reagent was refluxed in
      acetonitrile with an excess of triethylamine. These compounds were tested for
      their antioxidant activity by cyclic voltammetry, DPPH radical (DPPH*) assay and
      deoxyribose degradation assay. The minimum inhibitory concentration (MIC) of all
      compounds was evaluated against two yeast species, Saccharomyces cerevisiae and
      Candida albicans, and against bacteria Bacillus subtilis (Gram positive) and
      Escherichia coli (Gram negative). Their cytotoxicity was evaluated in
      fibroblasts. RESULTS: Among the synthetised compounds, five presented higher
      antioxidant activity than reference antioxidant Trolox and from these compounds,
      four presented antifungal activity without toxic effects in fibroblasts and
      bacteria. CONCLUSION: Four novel compounds presented dual antioxidant/antifungal
      activity at concentrations that are not toxic to bacteria and fibroblasts. The
      active molecules can be used as an inspiration for further studies in this area.

PMID- 30295193
TI  - Role of Porous Carriers in the Biopharmaceutical Performance of Solid Self
      microemulsion Preconcentrates of Canagliflozin1.
AB  - OBJECTIVE: The aim of the present investigation entails the development of solid
      SMEDDS for improving the oral bioavailability of canagliflozin using porous
      carriers. The previous patent (WO2017046730A1) was based on enhanced of
      solubility of canagliflozin through co-crystal formation. METHODS:
      Preconcentrates were prepared by employing Lauroglycol (80 mg), Tween 80 (300 mg)
      and Transcutol P (120 mg) and successfully adsorbed onto various hydrophilic and
      hydrophobic carriers. The prepared solid SMEDDS were characterized for various
      parameters to determine the optimized formulation. In vitro, ex vivo and in vivo
      studies were carried out to determine drug release kinetics, permeation and
      absorption rate, respectively. Stability of the formulation was investigated at
      45 degrees C/75% RH. RESULTS: The solid preconcentrates prepared with hydrophobic
      carriers exhibited desired attributes in uniform range. Neusilin adsorbed solid
      SMEDDS (S(N)SMEDDS) portrayed enhanced amorphization in XRD and DSC studies and
      found to be physically compatible in FTIR studies. SEM revealed colloidal
      particles having spherical morphology with negligible aggregation. Ex vivo
      permeation rate of the drug across excised intestinal segments (duodenum,
      jejunum, ileum and colon) was observed to be 3.72, 5.85, 4.51 and 3.0-fold,
      respectively, as compared to pure drug. TEM of reconstituted SMEDDS indicated
      nano-sized globules with negligible coalescence. Enhanced in vitro dissolution
      rate of optimized solid SMEDDS manifested in bioavailability enhancement of
      167.54% and 188.98 %, as compared to pure drug and marketed product. These
      studies further substantiate the lymphatic uptake of SMEDDS through chylomicron
      flow blocking approach. Establishment of Level A IVIVC showed uniform correlation
      between the in vitro dissolution efficiency and in vivo pharmacokinetic
      parameters. CONCLUSION: The present investigation reveals immense potential of
      solid SMEDDS in augmenting the oral bioavailability profile of poorly water
      soluble drug canagliflozin.

PMID- 30295194
TI  - [Impact of Arterial Hypertension on the Formation of the Risk of Mortality.
      Results of a 27-Year Prospective Study].
AB  - OBJECTIVE: to investigate the impact of arterial hypertension (AH) on formation
      of the risk of total and cardiovascular mortality. MATERIALS AND METHODS: The 27
      year cohort prospective study was conducted on the sample of unorganised
      population of Tomsk (n=1 546, age 20-59 years, 630 men, 916 women). At the first
      stage (1988-1991) we studied the prevalence of AH, at the second stage (2015) we
      investigated overall and cardiovascular mortality and the prognostic significance
      of AH in shaping mortality. Criterion of AH was blood pressure (BP) >=140/90 mm
      Hg or (in persons with BP.

PMID- 30295195
TI  - [Predictors of Obstructive Sleep Apnea Syndrome According to Results of Clinical
      Examintion and Ambulatory Blood Pressure Monitoring].
AB  - OBJECTIVE: to determine the predictors of obstructive sleep apnea syndrome (OSAS)
      basing on clinical examination, results of night pulse oximetry, daily dynamics
      of heart rate and blood pressure (BP) in men with newly diagnosed arterial
      hypertension (AH). MATERIALS AND METHODS: Men (n=197, mean age 40.1 +/- 8.4
      years) with newly diagnosed AH of mild (63%), moderate (26%), and severe (11%)
      degree. OSAS (Apnea-Hypopnea Index [AHI] >=5 events per hour) was diagnosed in
      156 patients (79%). Patients were divided into four groups depending on the AHI.
      The control group consisted of 31 men without AH and OSAS. Examination included
      standard clinical, laboratory and instrumental methods, as well as assessment of
      daytime sleepiness by the Epworth scale. Diagnostics of OSAS and 24-hour BP
      monitoring were performed on a portable multifunctional recorder. The duration of
      sleep was determined from the actigraphy data. Statistical analysis was carried
      out using descriptive statistics, correlation, regression and Receiver Operating
      Characteristic (ROC) curve analysis. RESULTS: In the studied sample of patients
      with AH prevailed individuals with central obesity and dyslipidemia. Mean
      estimate of daytime sleepiness assessed by the Epworth Sleepiness Scale was 7.8+/
      4.8 points. Of 156 patients with OSAS, its moderate and severe degree (AHI >=15)
      was diagnosed in 64%. Predictors of the presence of OSAS were the following: body
      mass index (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.05-1.22, p.

PMID- 30295196
TI  - [Combined Therapy of Arterial Hypertension With Triple Fixed-Dose Combination of
      Amlodipine/Indapamide/Perindopril Arginine in Real Clinical Practice: the
      Organization and the Main Results of the DOKAZATEL'STVO (Proof) Study].
AB  - AIM: to assess antihypertensive efficacy of the fixed-dose
      amlodipine/indapamide/perindopril arginine combination in hypertensive patients
      in real clinical setting. METHODS: We included in the 3-month clinical program 1
      599 patients with arterial hypertension (AH) (38.8 % men, mean age 61.6+/-10
      years). Primary outcomes were change of office and ambulatory (home blood
      pressure monitoring) systolic and diastolic blood pressure (SBP and DBP) from
      baseline to 3 months and rate of achievement of target BP.

PMID- 30295197
TI  - [Dynamics of Quality of Life in Patients With Aortic Stenosis After Aortic Valve
      Replacement With a Biological or Mechanical Prosthesis].
AB  - OBJECTIVE: To assess dynamics of the quality of life (QOL) in patients of the
      older age group of with initial aortic stenosis in 1, 3, and 5 years after
      replacement of the aortic valve (AV) with biological or mechanical prosthesis.
      MATERIALS AND METHODS: QOL was assessed in 282 patients who underwent aortic
      valve replacement with a biological or mechanical prosthesis. Criterion for
      inclusion in this retrospective single-center study was primary and elective
      nature of the operation. Patients with repeated interventions (early
      postoperative resternotomy, reosteosynthesis, repeat aortic valve surgery) were
      not included. Using the method of Propensity Score Matching, we distributed 151
      patients in whom the long-term results of AV replacement were analyzed according
      to age, gender, body mass index into groups of AV replacement with biological
      (group 1, n=74) and mechanical (group 2, n=77) prosthesis. RESULTS: In the early
      period after operation, there was no significant difference between groups in
      parameters of quality of life. During the observation period up to 3 years
      significant increases of parameters bodily pain (BP), vitality (VT), and mental
      health (MH) occurred in patients with biological prostheses, while physical
      functioning (PF) was higher in patients with mechanical prostheses. At follow-up
      to 5 years, indicators such as BP and role emotional functioning (RE) became
      higher in patients with mechanical prostheses. According to the conducted
      regression analysis the type of prosthesis affected the quality of life.
      CONCLUSIONS: 1) AV replacement with mechanical prostheses was associated with
      lowering of the physical component of health by 81.1%, and of the mental health
      component - by 56.6% per month; 2) significant difference in QOL between groups
      of patients with mechanical and biological prostheses could be detected only in 3
      years after the operation: parameters BP, VT and MH were significantly higher in
      patients with biological prostheses, while PF was higher in patients with
      mechanical prostheses; 3) in the longer observation period (up to 5 years)
      parameters BP and RE became higher in patients with mechanical prostheses.

PMID- 30295198
TI  - [Left Ventricular Myocardial Hypertrophy as a Result of Arterial Hypertension
      Among Mountain Shoria Population. The Role of Genetic Polymorphism].
AB  - OBJECTIVE: to establish associations of candidate genes ACE, AGT, AGTR1, ADRB1,
      ADRA2B, MTHFR and NOS3 polymorphisms with left ventricular myocardial hypertrophy
      (LVH) in patients with arterial hypertension (AH) among the indigenous (the
      Shors) and non-indigenous population of Mountain Shoria. MATERIALS AND METHODS:
      We examined 788 people in a clinical and epidemiological study of compactly
      living population in the remote areas of Mountain Shoria, located in the south of
      Western Siberia (468 members of indigenous ethnic group [the Shors], 320 members
      of non-indigenous ethnic group [90% Caucasian]). Diagnosis of AH was set in
      accordance with recommendations of Society of Cardiology of the Russian
      Federation/Medical Society of the Russian Federation on the Problem of Arterial
      Hypertension (RMOAG) (2010). Assessment of the structural and functional state of
      myocardium in patients with AH (n=201 among Shors and 158 among non-indigenous
      residents) was made by echocardiography. The polymorphisms of genes ACE (I/D, rs
      4340), AGT (c.803T>C, rs699), AGTR1 (A1166S, rs5186), ADRB1 (s.145A>G, Ser49Gly,
      rs1801252), ADRA2B (I/D, rs 28365031), MTHFR (c.677S>T, Ala222Val, rs1801133) and
      NOS3 (VNTR, 4b/4a) were tested by PCR. RESULTS: Among patients with AH LVH
      occurred more often within the indigenous (Shor) than in non-indigenous (non
      Shor) ethnic group (51.5 vs 42.2%, respectively, p=0.034). The frequency of
      homozygous genotype I/I of the ACE gene among AH patients with LVH in the Shor
      group was higher than in the non-Shor group (41.2 vs 19.3%, p=0.004). The
      prevalence of mutant genotype A/A of the ADRB1 gene was lower in the Shor
      compared to non-Shor group (53.6 vs 75.0%, p=0.014). The percentage of the
      carriers of prognostically favorable genotype 4b/4b of the NOS3 gene was higher
      in Shor than in non-Shor group (71.9 vs 52.7%, p=0.018), while the percentage of
      homozygous genotype 4a/4a carriers in the Shor group was lower (2.1% vs 18.2%,
      p=0.008). CONCLUSION: The following studied genes were found to be associated of
      with LVH: in the Shor cohort - the MTHFR gene (log additive model of
      inheritance), the A/G genotype of the ADRB1 gene (among people with normal body
      weight), the I/D genotype of the ACE gene (among men); in the non-indigenous
      cohort - D/D genotype of the ACE gene (the codominant model of inheritance), the
      NOS3 gene (the log additive model of inheritance).

PMID- 30295199
TI  - [Clinical-Epidemiological Program of Studying Psychosocial Risk Factors in
      Cardiological Practice in Patients With Arterial Hypertension and Ischemic Heart
      Disease: First Results of a Multicenter Study in Russia].
AB  - BACKGROUND: More than 10 years passed since conduction of the first clinical
      epidemiological study of prevalence of psychosocial risk factors (PSRF) in
      patients with arterial hypertension (AH) an/or ischemic heart disease in Russian
      Federation. PURPOSE: to assess current prevalence of PSRF in patients with AH/CHD
      and their relationship with traditional risk factors. MATERIALS AND METHODS:
      Patients with verified AH and/or CHD aged >=55 years were included into this
      cross-sectional study in 30 cities of Russia representing 7 federal districts
      according to the following procedure. In each city we selected 2-5 federal
      clinics - providers of primary medical care; in each of these clinics we at
      random invited 2-5 physicians to take part in this study. Each of these
      physicians for 1-2 days included 10 consecutive patients with AH and/or CHD.
      Information collected from patients comprised social demographic and clinical
      characteristics, risk factors, adherence to therapy; Hospital Anxiety and
      Depression Scale (HADS) was applied for detection of symptoms of anxiety and
      depression. Obtained information was used for analysis of prevalence of
      cardiovascular risk factors and their association with symptoms of depression and
      anxiety in a framework of Pearson linear and Kendall rank correlation analysis.
      RESULTS: Symptoms of anxiety of various severity (HADS-A>=7) were detected in
      42.2% of patients with AH and/or CHD, in 25.5% they were clinically significant
      (HADS-A>=11). Symptoms of depression of various severity (HADS-D >=7) were
      detected in 42.5% of patients with AH and/or CHD, in 16.3% they were clinically
      significant (HADS-D>=11). We also observed several significant associations of
      symptoms of depression and anxiety with traditional cardiovascular risk factors:
      low level of physical activity, elevated systolic and diastolic arterial
      pressure, level of total cholesterol, abdominal obesity; some unhealthy
      nutritional habits. CONCLUSIONS: Prevalence of symptoms of anxiety and depression
      was found to be high among ambulatory patients with AH and/or CHD. However, in
      this study it was lower compared with that reported by previous studies in
      Russia.

PMID- 30295200
TI  - [Metabolomic Profiling of Patients With Cardiovascular Diseases].
AB  - Cardiovascular diseases (CVD) are the main cause of death worldwide. A broad
      study of the pathogenetic mechanisms of the CVD onset and progression has led to
      understanding of the importance of endothelial dysfunction (ED) in these
      processes. During recent years intensive work has been conducted in the direction
      of searching for markers of ED. Metabolomics is an intensively advancing approach
      to early diagnostics of diseases. Metabolomic analysis based on mass spectrometry
      allows to study complete metabolic profiles and their deviations resulting from
      changes in expression of genes and RNA, protein activity, or environmental
      factors. Metabolomic analysis has already demonstrated significant results in the
      solving of different scientific and clinical problems. It appears to be a
      promising method for detecting early biomarkers of CVD. Various aspects of
      application of metabolomic profiling in the field of cardiovascular diseases are
      discussed in this article.

PMID- 30295201
TI  - [Position Statement on Challenges in Assessing Cause-Specific Mortality].

PMID- 30295202
TI  - [Annual Scientific Session of American College of Cardiology 2018: Results of
      Clinical Studies].
AB  - The article contains report of 15 most important clinical studies presented at 67
      th Annual Scientific Session of American College of Cardiology (Orlando, USA,
      March 10-12, 2018).

PMID- 30295203
TI  - [Atrial fibrillation as Risk Factor for Development of Cognitive Function
      Impairment and Dementia. Potential of Anticoagulant Therapy in Their Prevention].
AB  - This article presents an overview of data of Russian and foreign literature on
      possible associations between cognitive impairment and atrial fibrillation (AF).
      It includes modern classification of cognitive impairment, mechanisms of the
      effect of AF on cognitive functions and development of dementia, recommendations
      for the prevention of cognitive impairment in patients with AF. Special attention
      is paid to the assessment of cognitive status, and safe anticoagulant therapy,
      which is a priority in the prevention of cognitive impairment in patients with
      AF. Analysis of literature showed greater efficacy and safety of drugs from the
      group of Non-vitamin K Antagonist Oral Anticoagulants (NOAC), rivaroxaban in
      particular, in comparison with warfarin. Drugs from the NOAC group can be
      recommended for prevention stroke, cognitive impairment and dementia in elderly
      patients with AF.

PMID- 30295204
TI  - [The Problem of Adherence to Therapy in Cardiology].
AB  - This review article presents results of studies on adherence to drug therapy of
      patients after discharge from hospital. It contains analysis of the reasons for
      poor adherence, assessment of the impact of quality of adherence on the immediate
      and long-term results of surgical and medical treatment, structured methods of
      improvement of adherence to therapy; as well as economic aspects of the problem.

PMID- 30295205
TI  - [Double Blockade of Aldosterone Receptors as a Method of Elimination Negative
      Effects of Non-Steroidal Anti-Inflammatory Drugs in Chronic Heart Failure].
AB  - : The article deals with the dynamics of echocardioscopy indices during 1.5 years
      in a patient who underwent an acute myocardial infarction (MI). Two months after
      the MI left ventricular (LV) end-diastolic size and LV volume were 61 mm and 190
      ml, respectively; LV ejection fraction (EF) was 42%. At the background of maximal
      possible doses of ramipril, bisoprolol, and selective antagonist of aldosterone
      receptors eplerenone, and after revascularization, within eight months LV end
      diastolic size decreased down to 57 mm, LV volume - to 158 ml, and LVEF increased
      up to 51%. There was no change of potassium and creatinine blood serum levels.
      The situation changed dramatically after addition to ongoing therapy because of
      exacerbation of chronic osteochondrosis of ketoprofen 100, meloxicam 15 and
      tolperisone (Mydocalm) 450 mg/day. The patient noted an increase in dyspnea
      during walking, a decrease in exercise tolerance. LVEF fell to 36%, LV size
      increased up to values registered in 2 months after MI. There were no signs of
      overt fluid retention (no gain of weight, lower limbs edema, lung congestion on X
      ray, hepatomegaly at ultrasound examination). In 4 months after addition to
      therapy of a loop diuretic torasemide (5 mg) the cardio-hemodynamic parameters
      almost returned to values prior to administration of anti-inflammatory drugs.
      CONCLUSION: Loop diuretic (such as torasemide) can be recommended for elimination
      of negative consequences of the use of nonsteroidal anti-inflammatory drugs in
      patients with chronic heart failure.

PMID- 30295206
TI  - Parent-Reported Child Reactions to the September 11, 2001 World Trade Center
      Attacks (New York USA) in Relation to Parent Post-Disaster Psychopathology Three
      Years After the Event.
AB  - : IntroductionParents are a primary support for children following disasters,
      even though they face numerous challenges in addressing the physical and social
      consequences of an event. Parents who are directly exposed to a disaster and
      those who develop psychiatric disorders post-event are likely to be especially
      challenged and may be limited in their ability to support their children. This
      Brief Report describes a pilot study of survivors of the September 11, 2001 World
      Trade Center (New York USA) attacks who reported their own psychosocial
      consequences and the reactions of their children three years post
      event.HypothesesThe primary hypothesis of the study was that children's September
      11th reactions would be associated with their parents' psychiatric status.
      Secondary hypotheses were that the children's disaster reactions would be
      associated with direct exposure to the disaster in children and/or their parents,
      parent-child separation due to the disaster, and disaster-related school absence.
      METHODS: Approximately three years after the 2001 World Trade Center attacks, 116
      parents recruited from disaster-affected or disaster-related organizations were
      assessed using structured diagnostic interviews and queried about their
      children's (188 youths, aged three to 17 years at the time of the attacks)
      posttraumatic stress symptoms and behavioral changes. RESULTS: Almost one-half of
      the parents had a post-disaster psychiatric disorder, including major depression
      in 27% and disaster-related posttraumatic stress disorder (PTSD) in 11%. More
      than three-fourths of the children had at least one disaster-related
      posttraumatic stress symptom, and more than one-half experienced at least one
      post-disaster behavior change. A minority of the children were reported to have
      increased school behavior problems or a decline in their grades. Key correlates
      of children's disaster-related posttraumatic stress symptoms and post-disaster
      behavior changes were parent-child separation due to the disaster and parental
      post-disaster psychiatric disorders. CONCLUSION: Because parents provide primary
      caretaking and support for children post-disaster, addressing the needs of
      parents is critical to their ability to assist their children. Reducing parents'
      symptoms should increase their emotional availability and enhance their ability
      to address the needs of their children. Given the challenges in providing
      disaster interventions directly to children, especially when resources are
      limited, addressing parent psychopathology and distress (even in the absence of
      focusing on children's symptoms) may benefit children. PfefferbaumB, SimicZ,
      NorthCS. Parent-reported child reactions to the September 11, 2001, World Trade
      Center attacks (New York USA) in relation to parent post-disaster psychopathology
      three years after the event. Prehosp Disaster Med. 2018;33(5):558-564.

PMID- 30295207
TI  - The role of bicultural adaptation, familism, and family conflict in Mexican
      American adolescents' cortisol reactivity.
AB  - Scarce research has examined stress responsivity among Latino youths, and no
      studies have focused on the role of acculturation in shaping cortisol stress
      response in this population. This study assessed Mexican American adolescents'
      Mexican and Anglo cultural orientations and examined prospective associations
      between their patterns of bicultural orientation and hypothalamic-pituitary
      adrenal cortisol reactivity to an adapted Trier Social Stress Test. The sample
      included 264 youths from a longitudinal birth cohort study who completed the
      Trier Social Stress Test and provided saliva samples at age 14. The youths
      completed assessments of cultural orientation at age 12, and family conflict and
      familism at age 14. Analyses testing the interactive effects of Anglo and Mexican
      orientation showed significant associations with cortisol responsivity, including
      the reactivity slope, peak levels, and recovery, but these associations were not
      mediated by family conflict nor familism values. Findings revealed that
      bicultural youth (high on both Anglo and Mexican orientations) showed an expected
      pattern of high cortisol responsivity, which may be adaptive in the context of a
      strong acute stressor, whereas individuals endorsing only high levels of Anglo
      orientation had a blunted cortisol response. Findings are discussed in relation
      to research on biculturalism and the trade-offs and potential recalibration of a
      contextually responsive hypothalamic-pituitary-adrenal axis for acculturating
      adolescents.

PMID- 30295208
TI  - Mood stabilisers and risk of stroke in bipolar disorder.
AB  - BACKGROUND: Research on the risk of stroke following the use of mood stabilisers
      specific to patients with bipolar disorder is limited.AimsIn this study, we
      investigated the risk of stroke following the exposure to mood stabilisers in
      patients with bipolar disorder. METHOD: Data for this nationwide population-based
      study were derived from the Taiwan National Health Insurance Research Database.
      Among a retrospective cohort of patients with bipolar disorder (n = 19 433), 609
      new-onset cases of stroke were identified from 1999 to 2012. A case-crossover
      study design utilising 14-day windows was applied to assess the acute exposure
      effect of individual mood stabilisers on the risk of ischaemic, haemorrhagic and
      other types of stroke in patients with bipolar disorder. RESULTS: Mood
      stabilisers as a group were significantly associated with the increased risk of
      stroke in patients with bipolar disorder (adjusted risk ratio, 1.26; P = 0.041).
      Among individual mood stabilisers, acute exposure to carbamazepine had the
      highest risk of stroke (adjusted risk ratio, 1.68; P = 0.018), particularly the
      ischaemic type (adjusted risk ratio, 1.81; P = 0.037). In addition, acute
      exposure to valproic acid elevated the risk of haemorrhagic stroke (adjusted risk
      ratio, 1.76; P = 0.022). In contrast, acute exposure to lithium and lamotrigine
      did not significantly increase the risk of any type of stroke. CONCLUSIONS: Use
      of carbamazepine and valproic acid, but not lithium and lamotrigine, is
      associated with increased risk of stroke in patients with bipolar
      disorder.Declaration of interestNone.

PMID- 30295209
TI  - From birth to adulthood: anthropometric trajectories and their implications for
      chronic diseases in Guatemala.
AB  - The objective of this paper was to study nutritional status and growth, as
      measured by height and weight, over the life course and their connection with
      chronic diseases in Guatemala, a country with high levels of child undernutrition
      and adult overnutrition, using data from the Institute of Nutrition of Central
      America and Panama (INCAP) Nutrition Trial Cohort study. The study sample
      comprised a birth cohort of 1570 individuals who had data in the original 1969
      1977 survey as well as the 2002-2004 follow-up, allowing for an analysis of the
      nutritional transition from childhood to adulthood. The associations between
      childhood and adulthood anthropometrics were analysed, and the links of these
      with chronic disease indicators were assessed using multiple regression analysis
      and structural equation modelling. Moving upwards in nutritional status from
      childhood to adulthood was observed frequently in the study population. Unlike
      sex and place of residence, early anthropometrics were not generally found to be
      associated with adult body mass index (BMI). However, direct relationships were
      found between childhood nutritional status and growth and adulthood high-density
      lipoprotein (HDL) cholesterol, triglycerides and fasting blood glucose.
      Furthermore, these relationships were not mediated by BMI. The findings were not
      sensitive to the metric of childhood anthropometrics, as the use of length-for
      age, weight-for-age and weight-for-length all resulted in similar conclusions.
      These relationships demonstrate the importance of early childhood conditions for
      later-life outcomes. However, the lack of such relationships for blood pressure
      suggests that the biological links between childhood anthropometrics and various
      chronic diseases might vary.

PMID- 30295211
TI  - Primary care chaplaincy: an intervention for complex presentation.
AB  - : AimTo determine the responsiveness of primary care chaplaincy (PCC) to the
      current variety of presenting symptoms seen in primary care. This was done with a
      focus on complex and undifferentiated illness. BACKGROUND: Current presentations
      to primary care are often complex, undifferentiated and display risk factors for
      social isolation and loneliness. These are frequently associated with loss of
      well-being and spiritual issues. PCC provides holistic care for such patients but
      its efficacy is unknown in presentations representative of such issues. There is
      therefore a need to assess the characteristics of those attending PCC. The
      effectiveness of PCC relative to the type and number of presenting symptoms
      should also be analysed whilst evaluating impact on GP workload. METHODS: This
      was a retrospective observational study based on routinely collected data. In
      total, 164 patients attended PCC; 75 were co-prescribed antidepressants (AD) and
      89 were not (No-AD). Pre- and post-PCC well-being was assessed by the Warwick
      Edinburgh mental well-being score. Presenting issue(s) data were collected on a
      separate questionnaire. GP appointment utilisation was measured for three months
      pre- and post-PCC.FindingsThose displaying undifferentiated illness and risk
      factors for social isolation and loneliness accessed PCC. PCC (No-AD) was
      associated with a clinically meaningful and statistically significant improvement
      in well-being in all presenting issues. This effect was maintained in those with
      multiple presenting issues. PCC was associated with a reduction in GP appointment
      utilisation in those not co-prescribed AD.

PMID- 30295210
TI  - Ultrasonographic measurement of liver, portal vein, hepatic vein and perivisceral
      adipose tissue in high-yielding dairy cows with fatty liver during the transition
      period.
AB  - The aim of the present study was to evaluate the potential for diagnosis of fatty
      liver by means of ultrasonographic measurement of liver and perivisceral adipose
      tissue as an alternative to blood indicators of lipomobilization and liver biopsy
      in periparturient high-yielding dairy cows. Thirty cows were enrolled and divided
      into two groups. The evaluation of body condition score (BCS), non-esterified
      fatty acids (NEFA), beta-hydroxybutyrate (BHB), liver and perivisceral adipose
      tissue ultrasonographic measurement and histological liver lipid content (GdL)
      was performed at 15 +/- 5 d prepartum (T0), 10 +/- 2 d postpartum (T1), 30 +/- 2
      d postpartum (T2) and 50 +/- 2 d postpartum (T3). Mesenteric fat thickness (the
      thickness of the perivascular adipose tissue) measured on ultrasound was shown to
      be an independent determinant of fatty liver. The cut-off of the ultrasonographic
      evaluation of the liver may be useful as a first and practical approach in
      identifying fatty liver. In conclusion, a non-invasive and reliable diagnostic
      method for predicting the risk of fatty liver in high yielding dairy cows has
      been demonstrated.

PMID- 30295212
TI  - Tone-induced cervical and ocular vestibular-evoked myogenic potentials: comparing
      abnormalities in traumatic and non-traumatic vestibular disease.
AB  - BACKGROUND: Otolithic function is poorly understood, but vestibular-evoked
      myogenic potential testing has allowed the documentation of pathology in patients
      who complain of imbalance. METHODS: Seventy-four patients with traumatic and non
      traumatic vestibular disease were sequentially assessed at a tertiary referral
      neuro-otology unit in a teaching hospital. A detailed history of all patients was
      taken and standard vestibular assessment was conducted using the technique
      described in the companion paper. The results of both groups of patients were
      analysed and the rate of abnormalities was assessed. RESULTS: There was a high
      rate of abnormalities, including bilateral pathology, in a significant number of
      patients. Many patients in both groups inexplicably failed to recover.
      CONCLUSION: Vestibular-evoked myogenic potentials are helpful in documenting
      pathology, including bilateral pathology, which is outlined in the literature as
      being exceedingly difficult to compensate for.

PMID- 30295214
TI  - Trends in marketing foods to children in Slovenian magazines: a content analysis.
AB  - OBJECTIVE: Food marketing is an important factor influencing children's food
      preferences. In Slovenia the use of magazines is widespread among children. We
      investigated food advertising in children's and teens' magazines (CTM) in 2013
      and 2017. The penetration of food advertising was compared with magazines
      targeting the adult population. DESIGN: A repeated cross-sectional study.
      Magazines were searched for branded food references (BFR). All BFR were
      categorised and evaluated using the WHO Europe nutrient profile model. SETTING:
      Slovenia. SUBJECTS: All issues of CTM and a selected sample of issues of adult
      targeting magazines and newspapers published in Slovenia in 2013 and 2017.
      RESULTS: One hundred and seventy-five issues of CTM (ninety-two in 2013, eighty
      three in 2017) and 675 issues of adult-targeted magazines and newspapers were
      analysed (345 in 2013, 330 in 2017). In 2017, food advertising in CTM dropped
      notably but the opposite was found for adult-targeted magazines. Regular
      advertisements dominated in 2017 in CTM, while in 2013, 83 % of BFR types were
      games/puzzles, competitions and product placements. Chocolate and confectionery
      were the most advertised in CTM and food supplements in adults' magazines. Most
      foods in CTM were classed as 'not permitted' in both years (98 % in 2013 and 100
      % in 2017). CONCLUSIONS: The advertisements in CTM still mostly refer to
      unhealthy foods. The extent of food advertising has dropped considerably since
      2013. On the contrary, food advertising in printed media targeting adults has
      increased, chiefly referring to food supplements and foods that do not pass the
      WHO Europe nutrient profile model criteria.

PMID- 30295213
TI  - Biocultural determinants of overweight and obesity in the context of nutrition
      transition in Senegal: a holistic anthropological approach.
AB  - Senegal is experiencing a rising obesity epidemic, due to the nutrition
      transition occurring in most African countries, and driven by sedentary behaviour
      and high-calorie dietary intake. In addition, the anthropological local drivers
      of the social valorization of processed high-calorie food and large body sizes
      could expose the population to obesity risk. This study aimed to determine the
      impact of these biocultural factors on the nutritional status of Senegalese
      adults. A mixed methods approach was used, including qualitative and quantitative
      studies. Between 2011 and 2013, fourteen focus group discussions (n=84) and a
      cross-sectional quantitative survey (n=313 women; n=284 men) of adults in three
      different socio-ecological areas of Senegal (rural: n=204; suburban: n=206;
      urban: n=187) were conducted. Dietary intake (Dietary Diversity Scores), physical
      activity (International Physical Activity Questionnaire), body weight norms (Body
      Size Scale), weight and health statuses (anthropometric measures and blood
      pressure) were measured. Middle-aged and older Senegalese women were found to
      value overweight/obesity more than younger Senegalese in all regions. In
      addition, young urban/suburban adults had a tendency for daily snacking whilst
      urban/suburban adults tended to be less physically active and had higher
      anthropometric means. A binary logistic regression model showed that being
      female, older, living in urban/suburban areas and valuing larger body size were
      independently associated with being overweight/obese, but not high-calorie diet.
      Univariate analyses showed that lower physical activity and higher socioeconomic
      status were associated with being overweight/obese. Finally, overweight/obesity,
      which is low in men, is associated with hypertension in the total sample. The
      nutrition transition is currently underway in Senegal's urban/suburban areas,
      with older women being more affected. Since several specific biocultural factors
      jointly contribute to this phenomenon, the study's findings suggest the need for
      local public health interventions that target women and which account for the
      anthropological specificities of the Senegalese population.

PMID- 30295215
TI  - Drug-drug interactions and clinical considerations with co-administration of
      antiretrovirals and psychotropic drugs.
AB  - Psychotropic medications are frequently co-prescribed with antiretroviral therapy
      (ART), owing to a high prevalence of psychiatric illness within the population
      living with HIV, as well as a 7-fold increased risk of HIV infection among
      patients with psychiatric illness. While ART has been notoriously associated with
      a multitude of pharmacokinetic drug interactions involving the cytochrome P450
      enzyme system, the magnitude and clinical impact of these interactions with
      psychotropics may range from negligible effects on plasma concentrations to life
      threatening torsades de pointes or respiratory depression. This comprehensive
      review summarizes the currently available information regarding drug-drug
      interactions between antiretrovirals and pharmacologic agents utilized in the
      treatment of psychiatric disorders-antidepressants, stimulants, antipsychotics,
      anxiolytics, mood stabilizers, and treatments for opioid use disorder and alcohol
      use disorder-and provides recommendations for their management. Additionally,
      overlapping toxicities between antiretrovirals and the psychotropic classes are
      highlighted. Knowledge of the interaction and adverse effect potential of
      specific antiretrovirals and psychotropics will allow clinicians to make informed
      prescribing decisions to better promote the health and wellness of this high-risk
      population.

PMID- 30295216
TI  - Mental health outcomes at the end of the British involvement in the Iraq and
      Afghanistan conflicts: a cohort study.
AB  - BACKGROUND: Little is known about the prevalence of mental health outcomes in UK
      personnel at the end of the British involvement in the Iraq and Afghanistan
      conflicts.AimsWe examined the prevalence of mental disorders and alcohol misuse,
      whether this differed between serving and ex-serving regular personnel and by
      deployment status. METHOD: This is the third phase of a military cohort study
      (2014-2016; n = 8093). The sample was based on participants from previous phases
      (2004-2006 and 2007-2009) and a new randomly selected sample of those who had
      joined the UK armed forces since 2009. RESULTS: The prevalence was 6.2% for
      probable post-traumatic stress disorder, 21.9% for common mental disorders and
      10.0% for alcohol misuse. Deployment to Iraq or Afghanistan and a combat role
      during deployment were associated with significantly worse mental health outcomes
      and alcohol misuse in ex-serving regular personnel but not in currently serving
      regular personnel. CONCLUSIONS: The findings highlight an increasing prevalence
      of post-traumatic stress disorder and a lowering prevalence of alcohol misuse
      compared with our previous findings and stresses the importance of continued
      surveillance during service and beyond. DECLARATION OF INTEREST: All authors are
      based at King's College London which, for the purpose of this study and other
      military-related studies, receives funding from the UK Ministry of Defence (MoD).
      S.A.M.S., M.J., L.H., D.P., S.M. and R.J.R. salaries were totally or partially
      paid by the UK MoD. The UK MoD provides support to the Academic Department of
      Military Mental Health, and the salaries of N.J., N.G. and N.T.F. are covered
      totally or partly by this contribution. D.Mu. is employed by Combat Stress, a
      national UK charity that provides clinical mental health services to veterans.
      D.MacM. is the lead consultant for an NHS Veteran Mental Health Service. N.G. is
      the Royal College of Psychiatrists' Lead for Military and Veterans' Health, a
      trustee of Walking with the Wounded, and an independent director at the Forces in
      Mind Trust; however, he was not directed by these organisations in any way in
      relation to his contribution to this paper. N.J. is a full-time member of the
      armed forces seconded to King's College London. N.T.F. reports grants from the US
      Department of Defense and the UK MoD, is a trustee (unpaid) of The Warrior
      Programme and an independent advisor to the Independent Group Advising on the
      Release of Data (IGARD). S.W. is a trustee (unpaid) of Combat Stress and Honorary
      Civilian Consultant Advisor in Psychiatry for the British Army (unpaid). S.W. is
      affiliated to the National Institute for Health Research Health Protection
      Research Unit (NIHR HPRU) in Emergency Preparedness and Response at King's
      College London in partnership with Public Health England, in collaboration with
      the University of East Anglia and Newcastle University. The views expressed are
      those of the author(s) and not necessarily those of the National Health Service,
      the NIHR, the Department of Health, Public Health England or the UK MoD.

PMID- 30295218
TI  - Methotrexate for the treatment of unruptured tubal ectopic pregnancy.
AB  - CLINICIAN'S CAPSULE What is known about the topic? Methotrexate is widely
      accepted as first-line treatment of non-ruptured ectopic pregnancy and may be
      considered for women with a suspected ectopic pregnancy. What did this study ask?
      What are the outcomes of pregnant women with suspected ectopic pregnancy who
      received methotrexate as first-line treatment? What did this study find? Of
      patients treated with methotrexate, 18% went on to require surgical management,
      with 11.2% having ruptured on surgical evaluation. Why does this study matter to
      clinicians? Emergency department (ED) clinicians must be aware of the risk of
      methotrexate failure and have a high index of suspicion for patients returning to
      the ED.

PMID- 30295217
TI  - Circulating maternal and umbilical cord steroid hormone and insulin-like growth
      factor concentrations in twin and singleton pregnancies.
AB  - In addition to being associated with a higher risk of complications during
      pregnancy, twinning may also be a proxy for altered hormonal exposure for mothers
      and twin offspring, with implications for their health later in life. We compared
      maternal and fetal steroid hormone and insulin-like growth factor concentrations
      between singleton (n=62) and twin (n=41) pregnancies. Maternal concentrations of
      androgens, estrogens, insulin-like growth factor (IGF)-1, IGF-binding protein
      (BP)-3 and prolactin were quantified during the third trimester and at delivery,
      as well as in the fetal circulation at birth. Geometric means accounting for
      gestational age were calculated for hormone concentrations and compared between
      matched twin and singleton pregnancies. Most maternal hormone concentrations were
      modestly higher in twin than in singleton pregnancies in the third trimester
      (ranging from 8.3% for IGF-1 to 17.1% for estradiol) and at delivery (ranging
      from 11.1% for IGFBP-3 to 15.2% for estriol). Cord serum hormones were generally
      similar in twin and singleton pregnancies, except for IGFBP-3, which was 200%
      lower in twins. The modest differences in maternal hormones in late gestation
      seem unlikely to explain alterations in hormonally related disease risk in
      mothers of twins compared with singletons. The large deficit of IGFBP-3 in the
      fetal circulation of twins at birth may allow for sufficient concentrations of
      IGF-2 for growth and development in an environment of shared nutritional
      resources.

PMID- 30295219
TI  - Analysis of eye-tracking behaviours in a pediatric trauma simulation.
AB  - ABSTRACTEye-tracking devices are able to capture eye movements, which are further
      characterized by fixations. The application of eye tracking in a trauma setting
      has not been explored. Visual fixation can be utilized as a surrogate measure of
      attention during the management of a trauma patient. We aimed to determine the
      feasibility of using eye tracking and to characterize eye tracking behaviours of
      pediatric emergency medicine physicians during management of a simulated
      pediatric trauma patient. Each participant was equipped with a head-mounted eye
      tracking device during a standardized simulated pediatric trauma scenario. Each
      session was video recorded, with visual fixations defined as >0.2 seconds, and
      characterized by start time, duration, and the area of interest. Data from seven
      videos were analysed; 35% of eye fixations were directed towards the mannequin,
      16% towards the monitor, and 13% towards the bedside doctor. Visual eye tracking
      in a trauma simulation is feasible. Frequency of fixations tends to be highest
      towards the patient. Eye tracking within trauma simulation may provide new
      insights into quality improvement and inform advancements in pediatric trauma.

PMID- 30295220
TI  - Waist circumference, waist-to-height ratio and conicity index to evaluate android
      fat excess in Brazilian children.
AB  - OBJECTIVE: To evaluate the ability of anthropometric measurements to identify
      excess android fat and to propose cut-off points for excess central adiposity in
      children, according to age and sex. DESIGN: A cross-sectional study with children
      from a municipality of Minas Gerais, Brazil. Receiver-operating characteristic
      curve analyses were performed to evaluate waist circumference (WC), waist-to
      height ratio (WHtR) and conicity index (C-index) in estimating excess android fat
      by dual energy X-ray absorptiometry (DXA). SETTING: Vicosa, Minas Gerais, Brazil.
      SUBJECTS: Children aged 4-9 years (n 788). RESULTS: Overweight prevalence was
      29.1 % and android fat percentage was higher among girls. All central fat
      measurements were able to discriminate excess android fat in the age groups
      evaluated, especially WC and WHtR, with cut-off points showing good sensitivity
      and specificity overall. CONCLUSIONS: Because these methods are easy to obtain
      and inexpensive, it is possible to use WC, WHtR and C-index in population surveys
      to evaluate central obesity. The proposed cut-off points showed satisfactory
      values of sensitivity and specificity and can be used in epidemiological studies.

PMID- 30295221
TI  - Fruit and vegetable consumption is associated with improved mental and cognitive
      health in older adults from non-Western developing countries.
AB  - OBJECTIVES: Consumption of fruits and vegetables has been shown to contribute to
      mental and cognitive health in older adults from Western industrialized
      countries. However, it is unclear whether this effect replicates in older adults
      from non-Western developing countries. Thus, the present study examined the
      contribution of fruit and vegetable consumption to mental and cognitive health in
      older persons from China, India, Mexico, Russia, South Africa and Ghana. DESIGN:
      Representative cross-sectional and cross-national study.Setting/SubjectsWe used
      data from the WHO Study on Global Ageing and Adult Health (SAGE), sampled in 2007
      to 2010. Our final sample size included 28 078 participants. RESULTS: Fruit and
      vegetable consumption predicted an increased cognitive performance in older
      adults including improved verbal recall, improved delayed verbal recall, improved
      digit span test performance and improved verbal fluency; the effect of fruit
      consumption was much stronger than the effect of vegetable consumption. Regarding
      mental health, fruit consumption was significantly associated with better
      subjective quality of life and less depressive symptoms; vegetable consumption,
      however, did not significantly relate to mental health. CONCLUSIONS: Consumption
      of fruits is associated with both improved cognitive and mental health in older
      adults from non-Western developing countries, and consumption of vegetables is
      associated with improved cognitive health only. Increasing fruit and vegetable
      consumption might be one easy and cost-effective way to improve the overall
      health and quality of life of older adults in non-Western developing countries.

PMID- 30295222
TI  - Tourniquet Training Program Assessed by a New Performance Score.
AB  - : IntroductionApplication of a tourniquet is the cornerstone in management of
      combat-related extremity hemorrhages. Continuous and appropriate training is
      required to use tourniquets correctly.HypothesisThe aim of this study was to
      analyze the impact of a refresher training session, conducted directly in the
      theater of military operations, on the performance of tourniquet use. METHODS:
      During their deployment (October 2015-April 2016) in the Central African
      Republic, a first simulation session evaluated soldiers from two combats platoons
      for the application of the SOFFT (Special Operation Forces Tactical Tourniquet;
      Tactical Medical Solutions; Anderson, South California USA) tourniquet. After
      randomization, a R (+) group underwent a refresher training session, while a R (
      ) group did not. Two months later, a second simulation session was conducted for
      both groups: R (+) and R (-). A dedicated score (one to seven points), including
      delay and effectiveness, evaluated the soldiers' performance for tourniquet
      application. RESULTS: Twenty-six subjects were included in the R (+) group and 24
      in the R (-) group. Between the two assessments, the score improved for 61.5% of
      subjects of the R (+) group and 37.5% subjects of the R (-) group (P=.09). More
      particularly, the performance score increased from 4.2 (SD=1.4) to 5.5 (SD=0.9;
      P=.002) in subjects of the R (+) group whose last training for tourniquet
      application was over six months prior. CONCLUSION: A refresher tourniquet
      training session, conducted directly in a combat zone, is especially effective
      for soldiers whose last training session was over six months prior. A dedicated
      score can assess appropriately the performance of tourniquet training. MartinezT,
      DuronS, SchaalJV, BaudoinY, BarbierO, DabanJL, BoutonnetM, AussetS, PasquierP.
      Tourniquet training program assessed by a new performance score. Prehosp Disaster
      Med. 2018;33(5):519-525.

PMID- 30295223
TI  - Effectiveness of automated appointment reminders in Psychosis Community Services:
      A randomised controlled trial - CORRIGENDUM.

PMID- 30295224
TI  - Trauma and resilient functioning among Syrian refugee children.
AB  - Following the civil war in Syria, there has been a growing interest in the impact
      of war, violent conflict, and refuge on the development and mental health of
      refugee children in general and Syrian refugee children in particular. The
      objective of this paper is threefold: (a) to critically review the existing
      literature on the psychological functioning of Syrian refugee children, with a
      particular focus on those residing in the urban areas or camps in Turkey; (b) to
      identify the main theoretical and methodological problems of this emerging
      literature; and (c) to suggest guidelines for how to improve research and
      practice in this field. The reviewed literature predominantly focuses on
      psychological trauma, trauma-related symptomatology or other maladaptive
      functioning in children, and psychosocial interventions conducted toward
      alleviating these issues. This paper will summarize the research findings in the
      above-mentioned topics to discern what can be known from the existing literature
      on Syrian refugee children.

PMID- 30295225
TI  - Hungarian Managed Care initiatives between 2000 and 2007: regional health
      outcomes of the Hungarian Care Organizations.
AB  - BACKGROUND: In Hungary, since 1990, each government has tried to transform and
      rationalize the structure of health care. One of the reforms was the Care
      Managing Organization (CMO) programme introduced in 1999. OBJECTIVES: The aim of
      this paper is to describe the regional, environmental, structural and preliminary
      health related outcomes of the CMO in Bacs-Kiskun County (Central-Eastern
      Hungary). METHODS: First, cardiovascular screening programmes were organized for
      pre-screened and randomly selected populations of a total of 4462 persons. Seven
      years after completing the programmes, regional mortality data were analysed and
      compared. Second, nutritional and lifestyle counselling programmes with increased
      physical activity were organized for 2489 overweight or obese patients from the
      participating primary care practices. Anthropometric and laboratory data were
      examined after one and two years. RESULTS: First, for persons with higher
      cardiovascular risk, appropriate medical treatment was introduced, and after
      seven years, their mortality rates proved better than the regional and national
      data. Second, almost all measured anthropometric parameters improved (body mass
      index, body weight decrease) after the first year and this trend lasted till the
      end of the second year. CONCLUSIONS: According to the data of the National Health
      Insurance Fund, the average savings rate for all CMOs for the fiscal years 1999
      2007 was 4.94%. The highest rates of savings were realized in chronic and acute
      inpatient care and medical devices. In the end of 2008, by which time 14 CMOs had
      already covered 2.1million people, the programme was discontinued by the
      government, without a comprehensive evaluation of the experience and outcomes.

PMID- 30295226
TI  - The forgotten foundations: in core mental health services, no one can hear you
      scream.
AB  - SummaryThe Five Year Forward View for Mental Health (FYFVMH) was a welcome
      development in the emerging 'Parity of Esteem' agenda, but focused mainly on a
      select few specialist services; much more limited attention was given to 'core'
      general adult and older age mental health services, such as community mental
      health teams, crisis teams and in-patient units. This relative policy vacuum,
      when combined with prolonged financial pressures and limited informatics, has
      left core services vulnerable and struggling to meet growing demands, with little
      sense of hope, in contrast to some of the newer, 'shiny' specialist services
      growing around them. Policy makers need to recognise the growing crisis and take
      action, ensuring that any sequel to the FYFVMH redresses this imbalance by
      clearly prioritising core services as the vital foundations of the larger whole
      system. The potential benefits are huge and wide-ranging, but the harms of a
      second missed opportunity are perhaps even greater.Declaration of interestA.M.
      works in a National Health Service general adult community mental health team and
      is an elected member of the Royal College of Psychiatrists General Adult Faculty
      Executive Committee.

PMID- 30295228
TI  - The United States Virgin Islands and Hurricanes of 2017.

PMID- 30295227
TI  - Beverage consumption patterns and energy contribution from beverages per meal
      type: results from a national dietary survey in Sweden.
AB  - OBJECTIVE: Many studies of food intake have been performed and published in
      Sweden, but to our knowledge no studies have extensively explored the beverage
      consumption of the Swedish adult population. The present study aimed to describe
      the beverage consumption and the contribution of beverage energy (including
      alcohol energy) to total energy intake according to gender, region of living,
      meal type and day for a Swedish adult population. DESIGN: National dietary survey
      Riksmaten (2010-2011), collected by the Swedish National Food Agency. SETTING:
      Sweden. SUBJECTS: A total of 1682 participants (57 % women) reported dietary
      intake data during four consecutive days, specified by portion size, meal, time
      point, day of the week and venue. Meals were categorized as breakfast, lunch,
      dinner and 'other'.ResultThe beverage reported to be consumed the most was water
      (ml/d), followed by coffee. Men had a higher consumption of juice, soft drinks,
      beer, spirits and low-alcohol beer, while the consumption of tea and water was
      higher for women. For both genders, milk contributed the most to beverage energy
      intake. Energy percentage from beverages was higher at lunch and dinner during
      weekends for both genders. Participants from the biggest cities in Sweden had a
      higher consumption of wine for both genders and tea for men than participants
      from other regions. CONCLUSIONS: A considerable part of total energy intake was
      contributed by beverages, especially for men. Beverages can contribute to a more
      enjoyable diet, but at the same time provide energy, sugar and alcohol in amounts
      that do not promote optimal health.

PMID- 30295229
TI  - Advancing population health science to public health policy.

PMID- 30295231
TI  - Determinants of low birth weight in the context of maternal nutrition education
      in urban informal settlements, Kenya.
AB  - Inadequate knowledge in maternal nutrition is one of the determinants of low
      birth weight. However, little evidence is available on whether maternal nutrition
      counselling alone can influence birth weight among women from low socioeconomic
      households. This study assessed the effect of prenatal maternal nutritional
      counselling on birth weight and examined the related risk factors. A cluster
      randomized controlled trial was conducted to assess the effectiveness of home
      based maternal nutritional counselling on nutritional outcomes, morbidity,
      breastfeeding, and infant feeding practices by the African Population and Health
      Research Center in two urban informal settlements of Nairobi. The intervention
      group received monthly antenatal and nutritional counselling from trained
      community health volunteers; meanwhile, the control group received routine
      antenatal care. A total of 1001 participants were included for analysis. Logistic
      regression was applied to determine associations between low birth weight and
      maternal characteristics. A higher prevalence of low birth weight was observed in
      the control group (6.7%) than in the intervention group (2.5%; P<0.001). Logistic
      regression identified significant associations between birth weight and
      intervention group (adjusted odds ratio (AOR)=0.26; 95% confidence interval (CI),
      0.10-0.64); maternal height <154.5 cm (AOR=3.33; 95% CI, 1.01-10.96); last
      antenatal care visits at 1st or 2nd trimesters (AOR=9.48; 95% CI, 3.72-24.15);
      pre-term delivery (AOR=3.93; 95% CI, 1.93-7.98); maternal mid-upper arm
      circumference <23 cm (AOR=2.57; 95% CI, 1.15-5.78); and cesarean delivery
      (AOR=2.27; 95% CI, 1.04-4.94). Nutrition counselling during pregnancy reduced low
      birth weight and preterm births, which was determined by women of short stature,
      early stoppage of antenatal visit, and cesarean delivery.

PMID- 30295232
TI  - Examining the validity of the ADHD concept in adults and older adults.
AB  - OBJECTIVE: It is crucial to clarify the structure of attention
      deficit/hyperactivity disorder (ADHD) symptomatology in all age groups to
      determine how to best conceptualize this disorder across the lifespan. We tested
      the ADHD factor structure across adulthood and investigated independent
      associations with executive functions. METHOD: Data from 645 adults aged 18-59
      and 233 adults aged 60-85 were drawn from the Nathan Kline Institute Rockland
      Sample. Participants completed the Conners Adult ADHD Rating Scale and tests of
      executive functioning. Invariance of the ADHD factor structure was investigated
      using confirmatory factor analyses. Associations with cognition were explored
      using multiple linear regression. RESULTS: Results confirmed a bifactor model
      with 3 specific factors (inattention, hyperactivity, and impulsivity). Factor
      loadings and item intercepts were invariant across ages. Levels of hyperactivity
      and impulsivity were lower in older adults. Inattentive symptoms in young adults
      were positively related to cognitive flexibility. In older adults, ADHD symptoms
      predicted poorer working memory. CONCLUSION: ADHD symptoms manifest similarly
      across adulthood. The lack of robust associations between ADHD symptomatology and
      executive functions raises concerns about the usefulness of neuropsychological
      measures in diagnosing adult ADHD. These results support the validity of the ADHD
      concept in older adults but suggest a need for age-appropriate normative
      criteria.

PMID- 30295233
TI  - General practitioners cannot rely on reported weight and height of children.
AB  - AIM: The aim of this study is to investigate the differences between reported and
      measured weight and height for underweight, normal-weight, and overweight
      children, particularly in a general practitioner setting. BACKGROUND: Screening,
      signaling, and treatment of childhood obesity by the general practitioner depends
      on accurate weight and height measurements. METHODS: Data on reported and
      measured weight and height from a cohort including 715 normal-weight and
      overweight children aged 2-17 were used. Means of reported and measured weight
      and height were compared using the paired T-test. FINDINGS: Of the 715 included
      children, 17.5% were defined as being underweight, 63.2% normal-weight, and 19.3%
      overweight according to direct measured height and weight. In the age group 2-8
      years, parents of underweight children reported a significantly higher weight
      than measured weight [mean differences (MD) 0.32 kg (0.02, 0.62)], whereas
      parents of overweight young children reported a significantly lower weight [MD 
      1.08 kg (-1.77, -0.39)]. In the age group 9-17 years, normal-weight [MD -0.51 kg
      (-0.79, -0.23)] and overweight children [MD -1.28 kg (-2.08, -0.47)] reported a
      significantly lower weight than measured weight. CONCLUSIONS: General
      practitioners cannot rely on reported weight and height measures from parents and
      children. In case of suspected under- or overweight in children, it should be
      advised to measure weight and height in general practice.

PMID- 30295234
TI  - Varzaghan Earthquake Affected Mothers' and Their Newborns' Health More Severely,
      in Socioeconomically Vulnerable Area.
AB  - OBJECTIVE: We aimed to compare the pregnancy status of the pregnant women and
      birth status of their newborns, socioeconomic status, and access to health
      services, between high- and low-damage areas in Heris, affected by the Varzaghan
      Earthquake, 2012. METHODS: The study was conducted on pregnant women at any
      trimester of pregnancy (with complete medical profiles in local health centers)
      in August 2012 (time of the earthquake) who lived in Heris and delivered up to
      March 2013. Data were obtained on pregnancy- and infant-related variables,
      housing, socioeconomic status, and access to health services, including food
      supplies, before and after the earthquake. RESULTS: Family income and mothers'
      education were lower in highly damaged areas. Among these women, underweight at
      first trimester of pregnancy was higher, and weight gain during the last
      trimester was lower, compared with low-damage regions. Preterm delivery was
      higher in low-damage areas. Birth indices of the infants were not significantly
      different between the 2 areas; however, in highly damaged areas, moderate
      malnutrition was more prevalent among children under 1 year (weight-for-age) and
      under 2 years (height-for-age). CONCLUSIONS: Socioeconomic status of mothers was
      lower in highly damaged areas and might have played a role in their own and
      newborns' health status. (Disaster Med Public Health Preparedness. 2018; page 1
      of 8).

PMID- 30295235
TI  - [Construction of A Lentiviral Vector Carrying CUEDC1 Gene and Its Effect on the
      Proliferation and Colony-formating Ability of MOLT-4 Cells].
AB  - OBJECTIVE: To construct a lentiviral vector carrying human CUEDC1 gene, to
      establish leukemic cell line MOLT-4 stably expressing recombinant plasmid, to
      analyze the expression of CUEDC1 in MOLT-4 cells and to investigate its effect on
      the proliferation of MOLT-4 cells. METHODS: The CUEDC1 gene was amplified by RT
      PCR, and then was subcloned into the lentiviral vector pCDH to generate a
      lentiviral vector pCDH-CUEDC1. Recombinant lentivirus was generated by co
      transfection of 3 plasmids, and transfected into MOLT-4 cells. The Real-time PCR
      and Western blot were respectively applied to detect the expression of CUEDC1
      mRNA and protein, the CCK-8 and colony formation assay were used to evaluate the
      effect of CUEDC1 on proliferation of MOLT-4 cells. RESULTS: The recombinant
      lentiviral vector pCDH-CUEDC1 had been constructed successfully. After infection
      of MOLT-4 cells with the lentivirus, the recombinant plasmid could stably up
      regulate the expression of CUEDC1 and protein. The CCK-8 detection and colony
      formation assay showed that exogenous CUEDC1 could significantly promote cell
      growth and the colony formation of MOLT-4 cells. CONCLUSION: The recombinant
      lentiviral vector carrying human CUEDC1 has been successfully constructed,
      exogenous CUEDC1 can significantly promote cell growth and the colony formation
      of MOLT-4 cells.

PMID- 30295236
TI  - [Analysis of Heterogeneous Biological Characteristics and Prognosis-Related
      Factors in AL Patients with Mistranslation-Expressed Lymphoid and Myeloid-Related
      Antigen].
AB  - OBJECTIVE: To analyze the heterogeneous biological characteristics of acute
      leukemia (AL) patients with mistranslation expressed lymphoid and myeloid-related
      antigens, and it's prognosis-related factors. METHODS: Two hundred and fourteen
      AL patiens with mistranslation expressed lymphoid and myeloid-related antigens
      were grouped according to immunophenotypes, and the heterogeneous biologic
      charecteristics and prognosis related factors were analyzed, moreover the
      survival curves were drawn to analyze the survival of patiens. RESULTS: The
      immunophenotype in 214 cases was mainly cross-expression of myeloid and B lineage
      antigen (118 cases), followed by cross-expression of myeloid antigen and T
      lineage (88 cases), while the cross-expression of myeloid, T and B lineages, was
      less (only 8 cases). In ALL patiens with cross-expression of myeloid antigen, the
      CD33 was main type; while in AML patients with cross-expression of lymphoid
      antigen, CD7 was main type of lineage antigen, CD19 was main type of B lineage
      antigen. Among 214 AL patients, the cross-expression of CD55 and myeloid antigen
      was found in 30 cases, the cross-expression of CD7, CD19 and CD74 was observed in
      6 cases, the cross-expressions of CD7, CD34 and CD56 was detected in 4 cases.
      Among AML patients with lymphoid antigen expression, the recurrent chromosmal
      abnormalities were found in 16 cases; among ALL patients with myeloid antigen
      expression, the recurrent chromosomal abnormalities were observed in 10 cases.
      The mistranslation antigen expression existed in 26 patients with recurrent
      chromosomal abnormalities, the mistranslated CD33 and CD13 in ALL patients with
      myeloid antigen expression was common, while the mistranslated CD2, CD56 and CD19
      in AML patients with lymphoid antigen expression was common. As compared with
      patients without lymphoid antigen expression, the survival rate decreased
      significantly in patients with mistranslated CD7(+) and CD34(+) (both P<0.05).
      The logistic regression analysis showed that CD7, CD34 were main influencing
      factors for prognosis of AL patients (both P<0.05). CONCLUSION: The AL with
      mistranslation expressed lymphoid and myeloid antigens is a special kind of
      leukemia which possesses the heterogencous biological characteristcs and unique
      prognostic features, thus the immunophemotype of AL patients should be detected
      by flow cytometry. The existance of mistranlation-expressed differatiation
      antigens such as CD7 and CD34 is mainly influencing factors for the prognosis of
      AL patiens.

PMID- 30295237
TI  - [Primary Prophylatic Effect of Voriconazole Against Invasive Infection of
      Pulmonary Aspergillosis during Remission-Induction Chemotherapy for Acute Myeloid
      Leukemia].
AB  - OBJECTIVE: To evaluate the efficacy of primary prophylaxis of voriconazole
      against invasive infection of pulmonary aspergillosis (IPA) during remission
      induction chemotherapy (RIC) of patients with acute myeloid leukemia (AML).
      METHODS: Clinical data of 102 de novo AML patients who received primary anti-IPA
      prophylaxis during the first induction chemotherapy were analyzed
      retrospectively. All the cases were divided into voriconazole-treated group and
      posaconazole-treated group according to the prophylactic agent. The incidences of
      IPA and systemic antifungal treatment during induction chemotherapy were analyzed
      for both groups. RESULTS: Among 102 enrolled cases, 42 cases received
      voriconazole and other 60 received posaconazole as primary prophylaxis. IPA
      occurred in 3 cases of voriconazole group (1 probable, 2 possible); IPA occurred
      in 4 cases of posaconazose group, and all were possible cases. The incidence of
      IPA during remission-induction chemotherapy in variconazole group equaled to
      posaconazose group (7.1% vs. 6.7%) (P=0.925). Beside IPA cases, 2 cases in
      voriconazole group and 4 cases in posaconazole group received intravenous anti
      aspergillosis drugs preemptive treatment, and no significant difference of
      prophylactic success rate was observed between two groups (88.1% vs. 86.7%)
      (P=0.831). Visual disturbance was the most common adverse event occurred in
      voriconazole group, but no significant differences of incidences of other adverse
      effects were observed when compared with posaconazole group. CONCLUSION:
      According to similar prophylactic effect with posaconazole, voriconazole appears
      to be a good alternative for primary prophylaxis of IPA during remission
      induction chemotherapy in AML patients.

PMID- 30295238
TI  - [Effect of Additional Chromosomal Abnormalities on the Outcome of CML-CP Patients
      Receiving TKI Therapy].
AB  - OBJECTIVES: To explore the effect of additional chromosomal abnormalities on the
      prognosis and outcome of CML-CP patients receiving imatinib therapy. METHODS: The
      clinical and genetic data of 589 CML-CP patients receiving imatinib treatment
      between May 2009 and October 2014 in the 1st Affiliated Hospital of Soochow
      University were analyzed, the 589 patients were divided into 5 groups according
      to the karyotypes at the initial diagnosis. The OS(overall survival), PFS
      (progression-free survival), EFS (event-free survival), Cumulative MMR (major
      molecular remission) and Cumulative CCyR (complete cytogenetic remission) were
      calculated by using the Kaplan-Meier method and compared by using the log-rank
      text by Graphpad 6.0. The chi2 test was used to compare the frequency of optimal
      molecular response at 3, 6, 12 months among the 5 groups. RESULTS: There was
      significant difference about the frequency of optimal molecular response at 3 and
      6 months between CML-CP patients with additional chromosomal abnormalities and
      those with classic t(9;22) [50%(12/24) vs. 73.94%(261 /353), P<0.05; 50%(10 /20)
      vs. 72.05%(232 /322) (P<0.05)], and the same significant difference was found at
      6 months between the group with variant translocations and that with classic
      t(9;22) [53.3% (16 /30) vs. 72.05%(232 /322) (P<0.05)]. The P values of
      cumulative CCyR (P<0.05) and EFS (P<0.01) for 4 years were statistically
      significant between CML-CP patients with additional chromosomal abnormalities and
      the other 4 groups. Compared one to another, there was the significant difference
      in cumulative CCyR and EFS for 4 years between CML-CP patients with additional
      chromosomal.abnormalities and those with classic t(9;22) (47.25% vs.
      84.01%)(P<0.05); (75.03% vs. 90.01%)(P<0.01). CONCLUSION: The additional
      chromosomal abnormalities influence the outcome of CML-CP patients receiving
      imatinib treatment, which make poor prognosis.

PMID- 30295239
TI  - [Relationship between BCR-ABLIS and Prognosis and Affecting Factors for Prognosis
      in CML Patients Treated with TKI for 12 Months].
AB  - OBJECTIVE: To evaluate the long-term prognosis of CML patients whose BCR-ABL
      transcript level was warning and best response at 12 months of treatment with
      tyrosine kinase inhititor (TKI), and to investigate the factors affecting
      therapeutic efficacy and prognosis. METHODS: The clinical data of patients with
      newly diagnosed CML were analyzed retrospectively. According to BCR-ABL
      transcript level, the 80 patients were divided into group A and group B, the
      patients with BCR-ABLIS >0.1% and <= 1% (warning response) were entolled in group
      A, and the patients with BCR-ABLIS <= 0.1% (best response) were enrolled in group
      B as control. The ratio of patients with main molecular response (MMR) and deep
      molecular response (DMR), as well as aquistation rate and cummulative rate of MR4
      (DMR) at specified fine points in 2 groups were compared, the independent risk
      factors affecting the therapeutic efficacy and prognosis were analyzed. RESULTS:
      The MMR and MR4 of the B group at 15, 18 and 24 months after TKI treatment were
      significantly higher than those of the A group, and the patients in the B group
      reached MR4 faster. In the 3 months, 6 months and 12 months after the demarcation
      point (TKI 12 months), the A group was much less easy to obtain MR4 (P<0.05) than
      the B group. Through survival analysis, there were more patients in the B group
      than the A group at different time points to reach MR4, and the difference was
      statistically significant (P<0.01). The single factor analysis showed that the
      splenomegaly (below rib edge)> 10cm (P<0.01) and lactate dehydrogenase > 400 U/L
      (P<0.05) were the long-term warning factors for patients. Multivariate analysis
      showed that the size of the spleen was an independent factor (P<0.01) to affect
      the prognosis of the patients who had been warned for 12 months. CONCLUSION:
      Patients at 12 months warning effect are slower and less easier to get DMR, which
      has a poor long-term prognosis. The size of the spleen in the patient at warning
      for 12 months of treatment effect can predict the relatively poor long-term
      prognosis. For a patient with a 12 months response to the warning, an early
      replacement therapy is available on the basis of combining other factors..

PMID- 30295240
TI  - [Effects of EGCG on Proliferation, Cell Cycle and DAPK1 Gene Methylation of Acute
      Promyelocytic Leukemia NB4 Cell Line].
AB  - OBJECTIVE: To investigate the effects of epigallocatechin-3-gallate (EGCG) on
      proliferation and cell cycle of acute promyelocytic leukemia NB4 cell line and to
      clarify the molecular mechanism. METHODS: NB4 cells were treated with 0,50,75,100
      and 125umol/L of EGCG for 24, 48, 72 and 96 h, respectively. The proliferation
      level of NB4 cells was measured by CCK-8 assay. The cell cycle progression of NB4
      cells was assayed by flow cytometry. The mRNA expression levels of DNMT1, DNMT3a
      and DAPK1 were detected by RT-PCR. The methylation status of gene was tested by
      methylation specific PCR, and the expression level of DAPK1 protein was detected
      by Western blot. RESULTS: The proliferation and cell cycle progression of NB4
      cells treated with EGCG were inhibited and showed the characteristic of time
      dependent and dose-dependent manner. The expression level of DAPK1 and DNMT3a
      decreased in NB4 cells treated with EGCG. The expression level of DAPK increased
      in NB4 cells treated with EGCG, while the methylation of DAPK1 gene decreased.
      CONCLUSION: EGCG inhibits the proliferation and cell cycle progression of NB4
      cells by inhibiting the expression of DNMT1 and DNMT3a and down-regulating the
      methylation status of DAPK1 gene.

PMID- 30295241
TI  - [Effect of FBXW7 and NOTCH1 Mutations on Prognosis of Patients with Adult Acute T
      Lymphoblastic Leukemia].
AB  - OBJECTIVE: To investigate the mutation rate and mutation characteristics of FBXW7
      and NOTCH1 in adult T-ALL, and to study the effect of these 2 mutations on the
      clinical features and prognosis of patients with adult T-ALL. METHODS: The
      mutations of FBXW7 and NOTCH1 in 106 adult T-ALL patients were determined by gene
      sequencing of FBXW7 and NOTCH1 genes. and the clinical characteristics and
      prognosis were compared. RESULTS: Among the 106 cases of adult T-ALL, there were
      21 cases (19.8%) of FBXW7 mutation, 66 cases (62.3%) of NOTCH1 mutation and 18
      cases (17.0%) of FBXW7 / NOTCH1 double mutations. The 2-year cumulative overall
      survival rate and event-free survival rate of the patiants in FBXW7 / NOTCH1
      double mutant group were lower than those without mutations (27.8% vs
      70.3%)(P<0.01) and (16.7% vs 48.6%) ( P<0.01) respectivly, but the FBXW7 or
      NOTCH1 mutations had a little effect on the prognosis. The recurrence rate at
      mutant group was higher than that of the non - mutant group (77.8% vs 43.2%)
      (P<0.05). CONCLUSION: FBXW7 or NOTCH1 mutations can not be as the prognostic
      factors, but the FBXW7 / NOTCH1 double mutations may indicate poor prognosis.

PMID- 30295242
TI  - [Relationship between Immune Differentiation Antigen and Minimal Residual Disease
      in Childhood B-ALL].
AB  - OBJECTIVE: To determine whether immune differentiation antigen is related with
      clinical features and minimal residual disease (MRD) in childhood B-cell
      precursor acute lymphoblastic leukemia (B-ALL), who were treated with CCCG-ALL
      2015 protocol. METHODS: A retrospective analysis was conducted in 132 B-ALL
      children, Multiparametric flow cytometry was used to analyze the
      immunophenotypes. The children were divided into 2 groups by MRD>0.1% on d 19 and
      / or d 46 after chemotherapy. The Wilcoxon rank-sum test and chi2 test were used
      for the comparison between groups, and P<0.05 was considered statistically
      significant. RESULTS: CD19 (100%), CD22 (99.3%) and cCD79a (97.9%) were specific
      markers for patients with B-ALL, the CD13 and CD33 were mainly cross myeloid
      antigen. The significant differences were found between CD45- and CD45+ in WBC
      counts when being firstly diagnosed (Z=6.845, P<0.01), risk stratification
      (chi2=8.260, P<0.05) and prednisone poor responder (chi2=18.420, P<0.01).
      Significant differences were found between CD10- and CD10+ in age (Z=6.253,
      P<0.05), risk stratification (chi2=6.699, P<0.05) and MRD (chi2=4.951, P<0.05).
      CONCLUSION: In CCCG-ALL-2015 protocol, the CD10 relates with the early MRD,
      suggesting a better prognosis, and reducing the adverse effects of CD20 and cross
      myeloid antigen on prognosis.

PMID- 30295243
TI  - [Changes of T Cell Subsets and Their Relationship with Clinical Features and
      Prognosis in Patients with Acute Leukemia].
AB  - OBJECTIVE: To analyze the relationship between T cell subsets and clinical data.
      METHODS: mononuclear cells were collected from 103 patients with acute leukemia
      (AL) and 28 healthy volunteers, and percentage changes of CD3+CD4+, CD3+CD8+ and
      CD4+ CD25+ Foxp3+ cell subsets were assayed by flow cytometory. Relationship
      between the T subsets and clinical features of the patients was analyzed.
      RESULTS: Ratio of CD3+ T cells decreased more significantly in patients with >50%
      blast cells than that in patients with <50% blast cells, while the ratio of Treg
      between the 2 groups was not significantly different. Treg increased more
      statistically significantly in the patients with CD34+ leukemia cell than that
      with CD34- leukemia cells. In constrast to the relationship between prognosis and
      immune cells in the patients from 3 groups (low, intermediate and high-risk
      group) it was found that Treg cells increased more significantly in high-risk
      group than that in low-risk group. By continuously monitoring immune cells in 18
      patients, it was found that Treg cells gradually increased during the first 3
      courses of chemotherapy, then began to decreased in the 4th course, finally
      approached gradually to the normal value in the 6th course, and this change
      correlated with the clinical remission after chemotherapy. Treg cell number in
      the patients with AL was significantly higher than that in healthy controls, and
      Treg cell number during the onset and recurrence was significantly higher than
      that in the period of complete remission (continuous remission for over 6
      months). Compared with the changes of immune cell number between different types
      of disease, it was found that Treg cells were increased more significantly in
      acute myeloid leukemia (AML) than that in acute lymphoblastic leukemia (ALL).
      Proportion of Treg cells, Treg/CD4 decreased more significantly after the 1st
      course of chemotherapy in the group with complete remission (CR) than that in the
      group without CR. The complete remission rate and recurrence rate were 68.9% and
      20% respectively in the group with >10% Treg cells, while the complete remission
      rate and recurrence rate were 85.7% and 7.69% respectively in the group with.<10%
      Treg cells. In comparison of the 6 recurrent patients with 32 patients with
      sustained CR, it was found that the ratio of Treg cells and Treg/CD4 was
      increased more significantly in the patients with relapse than that with CR and
      in control group. CONCLUSION: Dynamic change of Treg cells in the peripheral
      blood was closely related with clinical feature, recurrence and prognosis in the
      patients with acute leukemia.

PMID- 30295244
TI  - [Effect of PD-L1 Expression on Activity of NK Killing AML Cell Lines and Its
      Mechanisms].
AB  - OBJECTIVE: To expolore the effect of programmed death receptor ligand 1 (PD-L1)
      expression level on killing effect of different cell lines of acute myeloid
      leukemia (AML) and its possible mechanism. METHODS: Peripheral blood from healthy
      individuals was collected routinely; NK cells were isolated using immunomagnetic
      beads; PD-L1 expression level was detected by flow cytometry; the killing effect
      of NK cells on acute myelogenous leukemia cell lines was evaluated with LDH
      release method and monoclonal antibody blocking experiment; the expression levels
      of IFN-gamma and IL-2 in the supernatants from the co-cultured effector/targer
      cells were measured by ELISA. RESULTS: The ratio of CD3-CD56+NK cells increased
      from (12.44+/-3.48)% to (71.29+/-5.65)%. The flow cytometry showed that KG-1a
      cells lowly expressed PD-L1 (8.35+/-4.12)%, but the THP cells a highly expressed
      PD-L1 (76.42+/-26.54)%. Meanwhile, the NK cells displayed a more efficient
      killing effect on KG-1a cells than that of THP1 cells (P<0.05). Moreover, PD-L1
      monoclonal antibody could reinforce NK cell killing effect and, promote the
      secretion of IFN-gamma and IL-2 in 5 acute myelogenous leukemia cell lines to
      varying degree. CONCLUSION: The killing effect of NK cells on acute myelogenous
      leukemia cell line is inversely proportional to PD-L1 expression; blocking PD1/PD
      L1 binding can significantly enhance the killing efficiency of effector-target
      cells, which way be related with promoting the release of IFN-gamma and IL-2.

PMID- 30295245
TI  - [Expression of EVI1 in Bone Marrow of Patients with AML and ALL and Its
      Correlation with Leukemia Subtyping, Clinical Features and Prognosis of
      Patients].
AB  - OBJECTIVE: To explore the expression of EVI1 gene in AML and the ALL patients'
      bone marrow cells, and its correlation with the leukemic typing, clinical
      characteristics and prognosis. METHODS: Three hundred and thirty-three cases of
      leukemia in our hospital from 2012 to 2016 were enrolled in this study. Among
      them there were 263 cases of AML, 70 cases of ALL, and 13 volunteers were
      selected as normal controls. The bone marrow samples of the patients and
      volunteers were aspirated. Firstly, the blood mononuclear cells(PBMNC) were
      separated from the samples through the Ficoll-Hypaque density gradient
      centrifugation. Secondly, the total DNA was extracted, and the expression of EVI1
      mRNA were assayed by real-ime quantitative PCR, which help to find out the EVI1
      mRNA expression difference between AML and ALL. Finally, the correlation of EVI1
      expression with the acute leukemia typing, clinical characteristics and prognosis
      were analyzed by a series of statistical method. RESULTS: Based on the expression
      levels of the EVI1 mRNA determined by real-time quantitative PCR, the expression
      levels in AML and ALL were both higher, but without significant difference. The
      rates of both EVI1 mRNA overexpression and low expression of the EVI1 mRNA in AML
      patients were higher than those in AML group, however, the rate of normal
      expression in ALL group was statistically significantly lower than that in the
      AML. The level of Plt in patients with AML-M1 and T-ALL positively correlated
      with the level of EVI1 expression(r=0.393,P<0.05;rho=0.442,P<0.05)while the level
      of blasts(%) in patients with AML-M3 negatively correlated with the level of EVI1
      expression. The expression of EVI1 correlated with the age of patients(chi2
      =6.684,P<0.05). The prognosis of AML patients with high expression of EVI1 mRNA
      was poor(Log-Rank test,P<0.05)and AML-M3 patients with high expression of EVI1
      had a significantly poorer prognosis than that of patients without high
      expression(Log-Rank test,P<0.01). CONCLUSION: In expression level of EVI1 no
      difference has been found in AML and ALL, but the distribution of EVI1 expression
      shows obvious difference and the difference correlats with the age of patients,
      at the same time, the some clinical features and subtype of acute leukemia
      correlate with the expression level of EVI1.

PMID- 30295246
TI  - [Effects of Tcd A on Rho GTPases and the Cytoskeleton of Leukemia Cell Line
      K562].
AB  - OBJECTIVE: To investigate the effect of clostridium difficile toxin A(TcdA) on
      the Rho GTPases and the cytoskeleton in K562 cells. METHODS: K562 cells were
      cultured in vitro with different concentration of TcdA.The effect of TcdA
      proliferation of cells was detected by MTT method after the K562 cells were
      stimulated with TcdA for 24,48 and 72h; the expression of cdc42, RhoA, Rac1 mRNA
      was assessed by RT-PCR; the changes of the microtubule, the microfilament were
      observed by confocal laser scanning microscopy. RESULTS: The proliferation of
      K562 cells was inhibited after exposure to TcdA for 24, 48 and 72h, and the
      inhibitory rate was 47.67% in the treatment for 48 h. the cdc42,RhoA and Rac1
      mRNA expressions in the experimental groups decreased after treated with
      TcdA(P<0.05), which positively correlated with concentration of TcdA. Also, the
      microfilament decreased ,which was observed by confocal laser scanning
      microscopy. CONCLUSION: TcdA inhibites K562 cell proliferation and induces
      apoptosis, TcdA can change the cytoskeleton structure through the cytoskeletal
      protein genes cdc42 and RhoA, Rac1 mRNA expression,. It is related with cell
      microfilament content decreasing.

PMID- 30295248
TI  - [Value of 18F-FDG PET/CT Scan Quantization Parameters for Prognostic Evaluation
      of Patients with Diffuse Large B-cells Lymphoma].
AB  - OBJECTIVE: To investigate the prognostic value of 18F-FDG PET/CT scan
      quantization parameters, max standardized uptake value (SUVmax), metabolic tumor
      volume (MTV), total lesion glycolysis (TLG) and other clinical factors for
      prognostic evaluation of paticnts with diffuse large B-cell lymphoma (DLBCL).
      METHODS: PET/CT scan and clinical data of a total of 65 newly diagnosed DLBCL
      patients who received Rituximab plus cyclophosphamide, doxorubicin, vincristine
      and prednisone (R-CHOP) chemotherapy as first-line treatment were analyzed. All
      patients received a PET/CT scan at diagnosis and an interim PET/CT after 2-4
      circles of chemotherapies. The related parameters of SUVmax, MTV and TLG were
      acquired by analyzing and calculating the scan results. The receiver operating
      characteristic (ROC) curve was used to determine the optimal cut-off of
      parameters. Pearson chi-square test, Kaplan-Meier method and COX proportional
      hazard model were performed to analyze the prognostic value of PET/CT related
      parameters and clinical factors in progression-free survival (PFS). RESULTS: Age,
      B symptom, Ann Arbor stage and extra-nodal involvement in major organs
      significantly related with PFS (P<0.05), but the SUVmax didn't relalt with the
      prognosis. The cut-off values of MTV0, MTV1, TLG0 and TLG1 for disease recurrence
      or progression were 172.20cm 3, 4.32cm 3, 1043.33g and 14.07g. The lower MTV and
      TLG groups showed longer PFS significantly. In the multivariate Cox regression
      model, B symptoms, MTV1 and TLG1 were the independent prognostic risk factors.
      CONCLUSION: MTV and TLG at baseline and in the interim and NCCN-IPI correlate
      with disease prognosis. SUVmax related parameters hare no significant
      relationship with prognosis. Besides MTV and TLG during treatment are the
      independent prognostic risk factors suggesting more predictive value than NCCN
      IPI.

PMID- 30295247
TI  - [Analysis of Clinical Characteivstics and Therapeutic Efticacy of 54 Patients
      with Mantle Cell Lymphoma].
AB  - OBJECTIVE: To analyse the clinical characteristics and therapeutic efticacy of
      patients with mantle cell lymphoma(MCL). METHODS: The clinical data including
      cliniced parameters and laboratorial test results of 54 patients with MCL were
      collected and restrospectively analyzed to clarity the clinical characteristics
      of MCL and to evaluate the survival and factors affecting prgnosis of patients.
      RESULTS: The incidence of MCL accounted for 4.0% of NHL in our center. The median
      age of MCL patients was 63 years old, the male and female ratio was 1.4?1. The
      MCL patients inIII-IV stage accounted for 96.3%; the extranodal organ involvement
      existed in 98.1% patients, the most common extranodal involvement sites were bone
      marrow(72.2%), spleen(51.9%), gastrointestinal tract(25.9%). The overall response
      rate(ORR) was 66.7%, among which the complete remisson (CR) rate was 37.1%, 3
      year and 5 year-progression free survival rate was 52.7% and 34.7% respectively,
      3 year and 5 year overall survival rate was 60.4% and 49.6% respectively. The
      therapeutic efficacy in chemotherapy combined with cytarabine group was suprior
      to that in chemotherapy group without cyteratine, the chemotherapy comtined with
      auto-HSCT could further improve the prognosis of patients. The unvariatc analysis
      showed that the KI67 level, B sgmptom, liver function, LDH and C-RP levels,
      initial therapeutic efficacy, high dose cytarabine regimen, auto-HSCT and relapse
      refractroy status were prognosis-related factors; the multi-variate analysis
      showed that the initial therapeutic efficacy and relapse rcfractory stasus were
      independent prognostic risk factors. Analysis showed that the surival of patients
      stratified according to MIPI and MIPI-c indexes was significantly different from
      that stratified by IPI index. CONCLUSION: The MCL patients commonly complicated
      by extranodal involvement and have poor prognoss. Using the chenotherapy regimen
      combined with high doge of cytarabine as induction therapy and auto-HSCT as
      consotidatory therapy shows the significont efficacy for survival of young
      patients with MCL. The MIPI and MIPIc indexe are more much suitable for prognosis
      evaluation of MCL patients.The initial therapeuntic efficacy and relapse
      refractrong status are the independant prognosis-related factors.

PMID- 30295249
TI  - [Clinicopathological Characteristics and Prognosis Analysis of the Patients with
      Plasmablastic Lymphoma].
AB  - OBJECTIVE: To evaluate the clinicopathological characteristics, treatment and
      prognosis of the patients with plasmablastic lymphoma(PBL). METHODS: The clinical
      and pathological data of 21 patients with PBL diagnosed and treated in our center
      between January 2009 and September 2017 were retrospectively analyzed. The
      clinical and pathological features, treatment and therapentic outcome were
      summarized and the high risk factors affecting the prognosis of patients were
      investigated. RESULTS: The 21 PBL patients included 12 males and 9 females, and
      their median age was 52 years old. The human immunodeficiency virus (HIV) was
      negative in all patients. The primary involved sites of 16 patients were
      extranodal, and the patients staged in III-IV accounted for 81%; 18 patients
      receved first-line chemotherapy with standard CHOP(E) (cyclophosphamide
      +epirubicin +vincristine +prednisone+/-etoposide). After treatment, only 1
      patient achieved complete response (CR), and 8 patients achieved partial response
      (PR). The median overall survival time was 6.3 months. Multivariate analysis
      showed the America Eastern Cooperative Oncology Group (ECOG) physical score and
      bone marrow infiltration were significant prognostic factors (P<0.01).
      CONCLUSION: Plasmablastic lymphoma frequently occurrs in the middle-old aged
      persons with all HIV negative. Primary extranodal lesions are frequent. Most
      patients were in advanced stage with poor treatment response. ECOG score>=2 and
      bone marrow infiltration are independent prognostic factors related with worse
      prognosis.

PMID- 30295250
TI  - [Expression of sB7-H4 in Serum and Lymphoma Tissues of Patients with Malignant
      Lymphoma and Its Value for Diagnosis and Re-Examine of Lymphoma].
AB  - OBJECTIVE: To study the soluble B7-H4 (sB7-H4) expression in serum and lymphoma
      tissues of patients with malignant lymphoma (ML) and its value for diagnosis and
      re-examination lymphoma. METHODS: The serum samples from 83 cases of ML were
      collected, among them 69 cases of newly diagnosed ML were enrolled in group A
      including 11 cases of Hodgkin's lymphoma (NHL group) and 58 cases of non
      Hodgkin's lymphoma (NHL group), the serum samples from 14 cases of relapsed ML
      were enrolled in group B; at the same time the serum samples of 50 healthy
      persons conformed by physical examination were collected and enrolled in control
      group. The double antibody sandwich ELISA was used to detect the serum level of
      sB7-H4 in each group, and immunohistochemistry method was used to detect the
      expression of sB7-H4 in malignant lymphoma and reactive lymphoid hyperplasia
      tissues. RESULTS: The serum level of sB7-H4 in the group A was significantly
      increased in comparison with the group B and control group, and the level of
      group B was significantly higher than that in the control group (P<0.05); the
      serum level of sB7-H4 in the NHL group was significantly increased in comparison
      with HL group and control group, and the level of HL group was higher than that
      of control group (P<0.05). The expression of sB7-H4 in reactive lymphoid
      hyperplasia tissues was negative, but the positive expression rate in malignant
      lymphoma tissues was 47.50%, suggesting the positive rate of sB7-H4 in malignant
      lymphoma tissues was significantly higher than that of reactive lymphoid
      hyperplasia tissues (P<0.05). CONCLUSION: The high expression of sB7-H4 in serum
      and lymphoma tissues of patients with malignant lymphoma has a certain value for
      the diagnosis and re-examination of patients with malignant lymphoma.

PMID- 30295251
TI  - [Effect of Chlorambucil on the Apoptotic Signaling Pathway in Lymphoma Cells].
AB  - OBJECTIVE: To study whether chlorambucil has apoptotic effect on the B cell
      lymphoma A20 cells and its exact mechanisms in apoptotic signaling pathway.
      METHODS: The experimental cells were treated with 20 MUmol/L chlorambucil, the
      control cells were treated with PBS. Annexin V-FITC Cell Apoptosis Detection Kit
      was used to examine cell apoptosis. Western blot was used to detect the
      expressions of active caspase-3, Survivin, NF-kappaB and pAKT. Real-time
      fluorescent quantitative PCR was performed to examine the mRNA expression of
      Survivin. RESULTS: Compared with the control group, the proportion of FITC+/PI+
      apoptotic cells and the expression of active caspase-3 (t=7.384, P=0.000) in the
      chlorambucil treatment group was significantly elevated. However, the expression
      of Survivin mRNA (t=4.384, P=0.000), protein expressions of survivin (t=12.360,
      P=0.000), NF-kappaB (t=5.462, P=0.000) and pAKT (t=7.183, P=0.000) in the
      chlorambucil-treated group all significantly decreased. CONCLUSION: The
      chlorambucil can induce the apoptosis of lymphoma cells, its mechanism may
      related with inhibition of PI3K/AKT signaling pathway, and expression of NF
      kappaB and survivin.

PMID- 30295252
TI  - [Effect of Autologous Hematopoietic Stem Cell Transplantation on Recurrent
      Refractory B Cell NHL and Its Factors Influencing Prognosis].
AB  - OBJECTIVE: To analyze the effect of autologous hematopoietic stem cell
      transplantation in the treatment of patients with recurrent refractory B cell non
      Hodgkin's lymphoma (NHL) and the related factors affecting the prognosis.
      METHODS: The clinical data of 47 cases of recurrent refractory B cell NHL treated
      in our hospital were retrospectively analyzed. Survival curves were drawn by
      Kaplan-Meier, and survival analyses were performed. Univariate and multivariate
      analyses were used to analyze the prognostic factors. RESULTS: The complete
      remission rate was 51.06% before autologous hematopoietic stem cell
      transplantation, but it increased to 65.96% after transplantation. The median
      survival time was 21 months, the 3 years progression-free survival rate was
      40.43%, and the 3 years overall survival rate was 48.94%. The results of
      unvariate analysis showed that no using the rituximab in the first treatment and
      incomplete remission shown by PET/CT before transplantation all were the risk
      factors (P<0.05) affecting the prognosis. By multifactor analysis, it was found
      that the incomplete remission shown by PET/CT before transplantation was a risk
      factor for the prognosis(P<0.05). CONCLUSION: The application of autologous
      hematopoietic stem cell transplantation for patients with relapsed and refractory
      B cell NHL can improve the clinical efficacy, and the incomplete remission shown
      by PET/CT before transplantation is more adverse to the patients' prognosis.

PMID- 30295253
TI  - [Effect of PD-1, FOXP3 and CSF-1R Protein Expression on the Prognosis of Patients
      with Hodgkin's Lymphoma].
AB  - OBJECTIVE: To investigate the effect of the expression of colony-stimulating
      factor 1 receptor (CSF-1R), forkhead box protein 3 (FOXP3) and programmed death 1
      (PD-1) protein on the prognosis of patients with Hodgkin's lymphoma. METHODS: The
      clinical features and treatment schemes of 54 patients with Hodgkin's lymphoma
      treated in our hospital were recorded, the specimens were collected and the
      relevant micro-environment prognostic factors such as the protein expression of
      CSF-1R, FOXP3 and PD-1 were detected by immunohistochemical staining, and EB
      virus and EB virus-encoded RNA (EBER) were detected by in situ hybridization; the
      correlation between CSF-1R, FOXP3, PD-1 protein expression with prognosis of
      patients with Hodgkin lymphoma were analyzed; both the unvariate analysis and
      multivariate analysis (using Cox proportional hazard model) were uased to analyze
      the influence factors of prognosis. RESULTS: Among the 54 cases of Hodgkin's
      lymphoma, 22 cases (40.74%) were positive for CSF-1R, 28 cases (51.85%) showed
      high expression of FOXP3 and 9 cases (16.67%) were positive for PD-1. Unvariate
      analysis revealed that the international prognostic index (IPI) score, EBER and
      FOXP3 protein expression were the effecting factors of progression-free survival
      (PFS) of patients with Hodgkin's lymphoma (all P<0.05); clinical staging (Ann
      Arbor stage), IPI score, EBER, CSF-1R and FOXP3 protein expression were the
      effecting factors of overall survival (OS) (all P<0.05). Multivariate analysis
      (Cox proportional hazard model) results showed that the EBER state was the
      effecting factors of PFS and OS in patients with Hodgkin's lymphoma (P<0.05); the
      expression of FOXP3 protein was the effecting factors of PFS (P<0.05); Ann Arbor
      stage and the expression of CSF-1R protein were the effecting factors for OS
      (both P<0.05). CONCLUSION: CSF-1R and FOXP3 closely relate with the prognosis of
      the patients with Hodgkin's lymphoma, which can provide a basis for targeted
      therapy of this disease.

PMID- 30295254
TI  - [T-Lymphoblastic Lymphoma Combined with Acute Myeloid Leukemia].
AB  - OBJECTIVE: To investigate the diagnosis and treatment of patients with T
      lymphoblastic lymphoma(T-LBL)combined with acute myeloid leukemia(AML). METHODS:
      The clinical features of 4 patients with T-LBL combined with AML were
      retrospectively analyzed, Among them the case 1 and 2 were synchronous
      occurrence,and case 3 and 4 were sequentially occurred. Especially for former 2
      patients,the dliagnosis differentiated from the involved lymph node of AML is
      important. RESULTS: The biopsies, immunohistochemical(IHC)test and T-cell
      receptor(TCR)gene rearrangement of the lymph node have been re-evaluated in our
      institulion. The diagnosis of T-LBL was confirmed. The diagnosis of AML was based
      on morphology,cytochemistry,immunophenotypy,karyotype and fusion gene of cells.
      The biphenotypic and bilineal types were found by flow cytometriy(FCM). The
      diagnosis of mixed acute leukemin(MAL)was confirmed. All the patients received
      chemotherapy,all of which died from leukemia. The survivnl duration was 2 to 5
      months from the diagnosis of AML. CONCLUSION: T-LBL combined with AML is an
      aggressive disease with am unfarourable prognosis, The new therapies should be
      designed to treat these rare cases.

PMID- 30295255
TI  - [Hemaorheology, Coagulation and Clinical Features of Malignant Lymphoma Combined
      with Venous Thromboembolism].
AB  - OBJECTIVE: To explore the hematological and clinical features of patients with
      malignant lymphoma (ML) combined with venous thromboembolism (VTE). METHODS:
      Sixty patients with ML combined with VTE in our hospital from May 2014 to May
      2016 were enrolled in ML+VTE group, out of them 42 patients were males and 18
      patients with females; another 60 patients with ML alone were enrolled in control
      group, out of them 43 patients were males and 17 patients females. The
      hematological, coagulation and clinical datas of all the patients were collected
      and then retrospectively analyzed. RESULTS: About 81.54% of the patients in
      ML+VTE group were found in Stage IIIB-IV tumor, and about 66.67% patients were
      found after ML was diagnosed; about 85.00% were with deep vein thrombosis (DVT),
      10.00% were with pulmonary embolism (PE), and 5.00% were complicated with both
      DVT and PE. Common DVT locations in 56.67% cases were the upper limb and the neck
      vein(56.67%); The total effective rate of the cases with DVT was 49.02%, and the
      rate of cases with PE was 14.29%, and 0 in the cases with both DVT and PE, the
      difference was statistically significant (chi2=72.650, P<0.001). Compared with
      the patients of control group, the levels of platelet aggregation, D-dimer, high
      cut blood viscosity, low cut blood viscosity, plasma viscosity, hematocrit,
      assembly index of erythrocyte, and rigidity index of erythrocyte were higher in
      patients of ML+VTE group (P<0.05), and APTT, erythrocy tesed imentation rate,
      deformability index of erythrocyte, and average velocity of blood flow were
      reduced, the differences were statistically significant (P<0.05). CONCLUSION:
      Hemaorheology and coagulation of patients with ML combined with VTE indicate
      changes in the sensitivity state of thromboembolism; DVT, which is commonly
      manifested in the upper limb and the neck vein, and it mainly observed in
      patients with end-stage.

PMID- 30295256
TI  - [Detection of the Cytogenetic Aberrations in Multiple Myeloma by Using Microrray
      Comparative Genomic Hybridization].
AB  - OBJECTIVE: To detect the molecular cytogenetic abnormalities of multiple myeloma
      (MM) by using microrray-based comparative genomic hybridization (array-CGH)
      technology and to investigate its value of application in MM. METHODS: The whole
      genoine copy number variants (CNV) of bone marrow samples acquired from 20 cases
      of newly diagnosed MM patients were detected by genome-wide hybridization and
      scanning by CytoScan 750K Array (Affymetrix). At the same time, the chromosome
      abnormalities of bone marrow cells were detected by karyotype analysis and FISH
      using 9 specific probes: D13S319, RB1, p53, 1q21, IgH, IgH/CCND1, IgH/FGFR3,
      IgH/MAF, IgH/MAFB. RESULTS: Among the 20 MM patients, the incidence of chromosome
      abnormalities detected by karyotype analysis, FISH and array-CGH were 15%, 65%
      and 90%, respectively. The types of CNV detected by array-CGH included the gain
      (106), loss (156) or UPD (23). There were many different CNVs in every
      chromosomes except chromosome 5, 9, 18, 21 and Y. Comparison of chromosome
      abnormalities detected by FISH and array-CGH showed that, the positive ratio of
      del (13q) was 35% and 40% respectively; the positive ratio of amp (1q) was 40%
      and 50% respectively; the positive ratio of del (17p) was both 15%. FISH
      detection showed 8 cases with IgH rearrangement, meansahile the array-CGH
      detection showed that 4 cases had amp (11q13) (CCND1 gene), 3 cases had amp
      (16q23) (MAF gene), 1 case had amp (4p16) (FGFR3 gene) and 2 cases had amp
      (20q12) (MAFB gene). Besides, many other new chromosome abnormalities were found.
      CONCLUSION: More than half of MM patients have cytogenetic changes, and most of
      them are complex chromosomal abnormalities. By using array-CGH, more chromosome
      abnormalities can be detected and more cytogenetic information can be provided
      for clinician.

PMID- 30295257
TI  - [Clinical Analysis on the Therapeutic Efficacy of Autologous Hematopoietic Stem
      Cell Transplantation in 56 Multiple Myeloma Patients].
AB  - OBJECTIVE: To evaluate the therapeutic efficacy and prognosis of autologous stem
      Hematopoietic cell transplantation (auto-HSCT) in multiple myeloma (MM) patients.
      METHODS: A retrospective study was conducted for 56 patients diagnosed with MM
      and then received auto-HSCT in our hospital from December 2008 to September 2016.
      RESULTS: All the patients successfully underwent hematopoietic reconstruction
      without transplantation-related mortality (TRM). The complete response (CR) rate
      of all the patients after induction chemotherapy was 23.2% (13/56), while the CR
      rate of these patients with auto-HSCT increased to 78.6% (44/56) (P<0.01). The CR
      plus VGPR (very good partial response) rates of these 56 patients after induction
      chemotherapy and auto-HSCT were 53.6%(30/56)and 94.6%(53/56) respectively
      (P<0.01). The median progression-free survival (PFS) time and median overall
      survival (OS) time were 37 and 71 months, respectively. The median PFS time in
      the patients with induction therapy containing bortezomib was 37 months, however,
      the median OS time did not reach to 71 months; the median PFS (P<0.01) and the
      median OS (P<0.01) in the patients with the induction chemotherapy without
      bortezomib was 27 and 51 months, respectively. Univariate analysis demonstrated
      that the patients maintained CR or VGPR after auto-HSCT or with less than 6
      cycles of induction chemotherapy significantly correlated with PFS (P<0.01).
      CONCLUSION: auto-HSCT can further increase the CR rate, prolong PFS and OS time.
      Sequential auto-HSCT after bortezomib-based therapy is the first line therapy for
      the transplant-eligible MM patients. Maintenance treatment is beneficial to the
      sustained CR+VGPR patients after auto-HSCT.

PMID- 30295258
TI  - [Chromosomal Abnormalities Associated with Clinical Outcome in Patients with
      Newly Diagnosed Multiple Myeloma].
AB  - OBJECTIVE: To investigate the prognostic value of karyotypic abnormalities in
      evaluation of prognosis of patients with multiple myeloma. METHODS: The clinical
      and laboratory data of patients with newly diagnosed multiple myeloma (NDMM) were
      retrospectively analyzed in our hospital from May 2010 to May 2016. Patients who
      carried t(4; 14), t(14; 16) or 17P- (at least one of them) were defined as the
      patients with high-risk karyotype, whereas patients characterized by the absence
      of the above-mentioned abnormalities were defined as patients with standard-risk
      karyotype. PFS (progression-free survival, PFS) and OS (over all survival, OS)
      time was compared between the 2 groups. RESULTS: There were 110 cases in the high
      risk group, and 302 cases in the standard-risk group. The clinical
      characteristics, such as age, sex, ISS stage and treatment regimen etc were not
      statistically different between 2 groups. The median OS time of patients in the
      high-risk and standard-risk groups were 42 months (CI 95%: 34.375-49.625 months)
      and 53 months (CI 95%: 46.310-59.690 months) (P<0.05). The median PFS time of
      patients in the high-risk group and standard-risk groups was 21 months (CI95%:
      17.198-24.802 months) and 27 months (CI95%: 23.406-30.594 months) (P<0.05).
      CONCLUSION: Among patients with newly diagnosed MM, the PFS and OS time in the
      patients with high-risk karyotype is shorter than that in patients with standard
      risk karyotyp.

PMID- 30295259
TI  - [Inhibitory and Inducing Effects of Emodin Derivative E11 on Proliferation and
      Apoptosis of Multiple Myeloma Cells].
AB  - OBJECTIVE: To screen the most strong emodin derivative inhibiting the
      proliferation of multiple myeloma(MM) cells and to explore the inhibitory and
      inducing effects of emodin derivatives on proliferation and apoptosis of MM cell
      lines RPMI 8226 and U266. METHODS: Sixteen emodin derivatives were designed and
      synthesized by using emodin as mother substance, then from which the emodin
      derivative E11 was screened for experiments. The MTT method and cell colony
      formation assay were used to observe the effect of E11 on proliferation of RPMI
      8226 and U266, the fluorescent microscopy with DAFI staining was used to observed
      the morphological changes of MM cells treated with emodin dervative 11, the DNA
      fragmentation detection was used to detect the inducing apoptosis effect of E11
      on RPMI 8226 and U266 cells treated with E11. RESULTS: The MTT assay showed that
      after the RPMI 8226 cells were treated with 16 kinds of emodin derivatives for 48
      hours, the 50% inhibition concentration(IC50) of 14 emodin dervatives was between
      0.83-34.68 umol/L, except E10 and E15 because their IC50 could not be calculated.
      The IC50 of E11 for RPMI 8226 and U266 cells were 0.831+/-0.0453 umol/L and
      1.039+/-0.093 umol/L, respectively. Cell colony formation assay showed that E11
      could inhibit RPMI8226 and U266 cells' colony formation in dose-.and time-
      dependent manner (r=0.72). Cell apoptosis was observed in RPMI8226 and U266 cells
      by DAPI staining , and also by the detection of DNA fragmentation. CONCLUSION: In
      the synthesis of 16 kinds of emodin derivatives, the inhibitory effect of E11 on
      prolife-ration of RPMI8226 cell was the strongest. E11 can remarkably inhibit
      proliferation and induce apoptosis of RPMI8226 and U266 cells.

PMID- 30295260
TI  - [Efficacy and Influencing Factors of Autologous Hematopoietic Stem Cell
      Transplantation for Multiple Myeloma: Retrospective Analysis].
AB  - OBJECTIVE: To analyze the clinical efficacy and possible influencing factors of
      autologous hematopoietic Stem cell transplantation (auto-HSCT) in the treatment
      of patients with multiple myeloma (MM). METHODS: Clinical data of 40 MM patients
      received auto-HSCT in the Department of Hematology of Henan Cancer Hospital from
      September 2010 to November 2017 were retrospectively analyzed, the clinical
      curative efficiency was summarized and the related factors were analyzed.
      RESULTS: The curative efficiency of the patients before transplantation was
      9(22.5%) with complete remission(CR), 5(12.5%) with very good partial
      remission(VGPR), 26(65%) with partial remission(PR), respectively, one of them
      was PR after 3 recurrences. The curative efficiency after transplantation was
      22(55%) with complete remission(CR), 12(30%) with very good partial
      remission(VGPR), 6(15%) with partial remission(PR), respectively. And 2 cases
      were CR after double transplantation. Median follow-up time was 28.4 (3.1 to 88)
      months,15 cases presented disease progression, 7 cases were dead, 3-year
      estimated progression-free survival(PFS) and overall survival(OS) rate were 45.1%
      and 82% respectively. Unvariate analysis showed that the OS was affected by ISS
      stage (P<0.05), CR and VGPR (P<0.05) after transplantation; PFS was affected by
      ISS stage (P<0.01), before transplantation induction therapy (27 cases with
      bortezomizomi or thalidomide) (P<0.05), disease risk stratification (6 cases in
      high risk group) (P<0.05) , CR and VGPR (P<0.05) before transplantation, CR and
      VGPR (P<0.01) after transplantation. Cox multivariate regression analysis showed
      that the independent prognostic factors for OS were ISS stage, CR and VGPR after
      transplantation; the independent prognostic factors for PFS were the CR, VGPR,
      ISS stage after transplantation and induction therapy before transplant.
      CONCLUSION: Auto-HSCT can improve the clinical efficacy and survival rate of MM
      patients; ISS stage, CR and VGPR after transplantation are independent prognostic
      factors for OS and PFS, and induction therapy before transplantation is also an
      independent prognostic factor for PFS.

PMID- 30295261
TI  - [Expression of IL-17 and MMP-13 in Bone Marrow Biopsy of Pafsents with Multiple
      Myeloma and Its Clicnical Significomce].
AB  - OBJECTIVE: To investigate the expression of interleukin-17(IL-17)and matrix
      metalloproteinase-13 (MMP-13)in bone marrow biopsy of patients with multiple
      myeloma(MM)and its clicnical siginficonce. METHODS: The expressions of IL-17 and
      MMP-13 in bone marrow biopsy of 47 patients with MM and 10 normal persons as
      controls were determined with immunohistochemical method. RESULTS: The mean
      optical density of IL-17+ and MMP-13+ in MM group was significantly higher than
      that in control group(P<0.01). The mean optical density of IL-17+ and MMP-13+
      positive expression in osteolytic lesions of MM group was significantly higher
      than that in patients without osteolytic lesions. The expression of NF-kappaB
      p65+ in MM group was significantly higher than that in control group(P<0.05);
      however the IL-17 level positively correlated with MMP-13 expression
      level(r=0.514) in MM group. The levels of IL-17 and MMP-13 in patients with
      ineffective treatment were very significantly higher than those in patients with
      effective trealment(P<0.01). CONCLUSION: The expression of IL-17 and MMP-13 in MM
      patients is significantly higher than that in the control group,and the
      expression of IL-17 and MMP-13 closely relate with MBD,which may be involved in
      the pathogenesis of MBD through NF-kappaB pathway,while the IL-17 and MMP-13 may
      serve as potential indicator for evaluation of therapeutic efficacy.

PMID- 30295262
TI  - [Effects of Luteolin on Proliferation and Programmed Cell Death of Human Multiple
      Myeloma Cell RPMI-8226].
AB  - OBJECTIVE: To investigate the effect of Luteolin on proliferation and cell death
      of human multiple myeloma cell line RPMI-8226 and its mechanisms. METHODS: The
      effect of Luteolin on the growth of human multiple myeloma cell line RPMI-8226
      was detected by CCK-8, and then the minimal effective concentration was
      determined and was used to treat RPMI-8226 cells. The effects of luteolin and
      chloroquine on expression of cleaved-caspase 3 and LC3 in RPMI8826 cells was
      detected by Western blot. RESULTS: The luteolin significant inhibited RPMI-8226
      cell proliferation in a dose-dependent manner. Treatment with lutedin 40-80umol/L
      for 24 hours and luteolin 20-80umol/L for 48 hours inhibited RPMI-8226 cell
      proliferation in a dose-dependent manner (24 h, r= -0.983; 48 h, r= -0.985).
      After treatment with lutelin 20umol/L for 48 h, the expression of cleaved
      caspase3 and LC3 II/I in RPMI 8826 cells significantly increased; after treatment
      with chloroquine at the same time, the expression of cleaved-caspase 3 and LC3
      II/I significantly decreased. CONCLUSION: Luteolin inhibits the proliferation of
      RPMI-8226 cells by inducing the pathways of both apoptosis and autophagy,
      moreover the actions of apoptosis and autophagy are interactive or/and promotive
      each other.

PMID- 30295263
TI  - [Variation of STAT3 Gene in Myleproliferative Neoplasms and Its Significance].
AB  - OBJECTIVE: To detect the mutation and single nucleotide polymorphisms of STAT3
      gene in the patients with myeloproliferative neoplasms (MPN), and to analyze the
      correlation between STAT3 gene and the subtypes of MPN. METHODS: A total of 147
      patients with MPN were selected, including 28 patients with polycythaemia vera
      (PV), 46 patients with essential thrombocythemia (ET), 10 patients with primary
      myelofibrosis (PMF), and 63 patients with chronic myeloid leukemia (CML); and 88
      healthy persons were used as normal control. DNA of all cases was extracted from
      bone marrow or peripheral blood, and JAK2V617F gene mutation was detected by
      allele-specific PCR, then 23 exons of STAT3 gene were amplified by PCR. Mutation
      and single nucleotide polymorphism of Rs2293152 of STAT3 gene were identified by
      DNA sequencing. RESULTS: STAT3 gene mutation was found in 8 patients with CML.
      The mutation rate was 12.7%. the missense mutation(S629T)as found in 3 cases, the
      synonymous mutation was found in 5 cases (Q469Q 3 cases, G618G 2 cases). One case
      had mutations at the both sites of S629T and G618G. No mutation of STAT3 gene was
      found in the normal control group. Rs2293152: detection showed that the G allele
      of CML group was significantly higher than that of normal control, PV, ET and PMF
      group (P<0.01), suggesting that the patients with Rs2293152 G allele were more
      likely to develop CML. The C allele of PV, ET and PMF group was significantly
      higher than that of CML group (P<0.05), suggesting that the patients with
      Rs2293152 C allele were more likely to develop PV, ET and PMF. The G allele
      fiequency of JAK2V617F-negative group was significantly lower than that of the
      normal control and JAK2V617F positive group (P<0.01), suggesting that the
      Rs2293152 G allele may be a factor protecting against JAK2V617F mutation.
      CONCLUSION: In MPN patients, STAT3 gene is unstable and prone to mutation. The
      different alleles of the Rs2293152 locus of the STAT3 gene are relates with
      different subtypes and JAK2V617F-negative MPN.

PMID- 30295264
TI  - [Clinical Features and Laboratory Data Analysis of Glucose-6- Phosphate
      Dehydrogenase Deficiency].
AB  - OBJECTIVE: To explore clinical features and laboratory data of glucose-6
      phosphate dehydrogenase(G6PD)deficiency and to investigate the relationship
      between them. METHODS: Clinical data of 43 patients with G6PD deficiency was
      analyzed, the statistical method was applied to investigate the relationship
      between clinical features and laboratory data. RESULTS: Among 43
      patients,neonatal jaundice occurred as the first symptom in 10 cases,while acute
      hemolytic anemia occurred as the first symptom in 23 cases. The major clinical
      symptoms of G6PD deficiency included icteric skin and/or sclera,dark
      urine,fever,gastrointestinal symptoms,fatigue and lethargy. Symptoms of 26
      patients were caused by obvious inducement,including fava
      beans(61.5%),infection(34.6%)and miocardial infarction(3.8%). All of 43 patients
      showed decreased G6PD activity,while the level of their indirect serum
      bilirubin(IBIL)was positively correlated with reticulocyte
      percentage(Ret%,r=0.5881,P=0.013) and mean corpuscular
      volume(MCV,r=0.6854,P=0.0024). Patients with neonatal jaundice as the first
      symptom,showed higher level of Ret%(P<0.01)and MCV(P<0.001)and low RBC
      count(P<0.01)and low Hb level(P<0.01). as compard with patients with acute
      hemolytic anemia as first symptome. CONCLUSION: Neonatal jaundice and acute
      hemolytic anemia are common clinical features of G6PD deficiency. Laboratory
      results of IBIL,Ret% and MCV have auxiliary value to evaluate the severity of
      hemolysis induced by G6PD deficiency. Patients with neonatal jaundice as their
      first symptom show more severe hemolysis than those only suffered from acute
      hemolytic anemia.

PMID- 30295265
TI  - [Effect of Graft Composition on Acute Graft-Versus-Host Disease in Aplastic
      Anemia after Haploidentical Hematopoietic Stem Cell Transplantation].
AB  - OBJECTIVE: To investigate the relationship between acute graft-versus-host
      disease and graft composition in patients with aplastic anemia(AA) after
      haploidentical hematopoietic stem cell transplantation. METHODS: Fifty-seven
      cases of AA after haploidentical hematopoietic stem cell transplantation were
      retrospectively analyzed. All the patients were divided into 2 groups according
      to whether presence or absence grade II-IV aGVHD, the relationship between aGVHD
      and graft composition was analyzed by comparing the differences of graft
      components between the 2 groups. RESULTS: Fourteen out of 57 patients had grade
      II-IV aGVHD and the other 43 did not have grade II-IV aGVHD. The mononuclear
      cells, CD3+, CD4+, CD8+, NK cells, NKT cells, B cells and Treg cells were not
      significantly different between the 2 groups (P>0.05), the CD34+ cell count in
      the patients with grade II-IV aGVHD was 3.85(1.73-10.61)*106/kg, which was
      significantly lower than that without grade II-IVaGVHD: 6.31(2.98-19.35)*106/kg
      (P<0.05). CONCLUSIONS: The incidence of grade II-IV aGVHD may be related with
      CD34+ cell count in AA after haploidentical hematopoietic stem cell
      transplantation..

PMID- 30295266
TI  - [Relationship of Blimp-1 Hypoexpression with Pathogenesis of Aplastic Anemia].
AB  - OBJECTIVE: To study the relationship of Blimp-1 hypoexpression with abnormality
      of Treg level and pathogenesis of aplastic anemia (AA). METHODS: The mouse model
      with AA was established by adminis tration of IFN-gamma combined with busulfan.
      The samples were collected at different day establishing AA model, and the spleen
      Treg number was detected, the Treg cells were sorted and expression level of prdm
      1 was detected. RESULTS: The number of Tregs in mice with AA was lower than that
      in control mice, moreover, the level of Treg decrease positively correlated with
      the AA severity (r=0.805), the higher the expression level of prdm-1, the higher
      the ratio of Treg/lymphocytes, showing positive correlation between them
      (r=0.548). CONCLUSION: Blimp-1 expression may promote the proliferation and
      differentiation of Treg. The hypoexpression of Blimp-1 mediates the pathogenesis
      of AA and promotes progression of AA through reducing the proliferation of Treg,
      and decreacing the number of Treg.

PMID- 30295267
TI  - [Epidemiological Survey of Thalassemia in Women of childbearing age in Quanzhou
      Area of Fujian Province in China].
AB  - OBJECTIVE: To investigate the gene prevalence and spectrum of thalassemia in the
      women of childbearing age in quanzhou area. METHODS: Venous blood of the women
      were collected for study, all subjects were registered in each county of quanzhou
      area by using cluster sampling. Both the mean corpuscular volume (MCV) and mean
      corpuscular hemoglobin (MCH) were used for screening thalassemia.Genotyping of
      the screened positive samples was performed by gap single polymerase chain
      reaction (gap-PCR) and reverse dot blot (RDB) hybridization.Unknown positive
      samples were analyzed with DNA sequencing. RESULTS: Out of all 7 082 samples,
      Three hundred and eighty four were identified as thalassemia gene carriers with a
      carrying rate of 5.42 %. The alpha and beta thalassemia were 3.21% and 2.15%
      respectively. --SEA /alphaalpha was the most common genotype with 68.72 % in
      mutation types of alpha thalassemia, In addition gene, 2 cases of -
      THAI/alphaalpha and 1 case of alphaalpha/alphaalphaalphaanti3.7 were also
      detected. IVS-II-654/N and CD41-42/N were the most common gentypes with 75.00 %
      in mutation types of beta thalassemia gene, 5 cases were found to be alpha beta
      compogite thalassemia. CONCLUSION: The carrying rate of thalassemia gene in
      quanzhou area is higher, and with the most common gentypes including --SEA
      /alphaalpha,IVSII-654(C->T)/N and CD41-42(-TTCT)/N. The study results are
      beneficial for the screening of thalassemia in the genetic consultation and the
      prenatal gene diagnosis.

PMID- 30295268
TI  - [Analysis of Correlation of Immune T Cell Subsets, TNF-alpha, IFN-gamma and sFas
      levels with Severity and Prognosis in Aplastic Anemia Patients].
AB  - OBJECTIVE: To explore the correlation of immune T cell subsets and expression
      levels of TNF-alpha, IFN-gamma and sFas with the severity and prognosis of
      aplastic anemia(AA) patients. METHODS: Ninety-five patients with aplastic anemia
      treated in our hospital were selected and enrolled in AA group, 43 cases of which
      were included in the acute group and 52 cases in the chronic group according to
      the disease status of patient's. Then, 50 cases of healthy volunteers in the same
      period were enrolled in the control group, and the changes of immune T cell
      subsets, and sFas serum TNF-alpha, IFN-gamma and levels of the 3 groups were
      compared. The ROC curve was used to analyze the value of each index for
      evaluating the severity of the disease, 95 patients with aplastic anemia were
      followed up and the Kaplan-Miere survival curve was used to analyze the effect of
      different index levels on the progression-free survival of the patients. RESULTS:
      the serum level of CD4+ level and CD4+ /CD8+ ratio in AA group were significantly
      lower than those in the control group (P<0.05), and the CD8+ level in AA group
      was significantly higher than that in the control group (P<0.05). The CD4+ level
      and CD4+ /CD8+ ratio in the acute group was significantly lower than those in the
      chronic group (P<0.05), and the CD8+ level in the acute group was significantly
      higher than that in the chronic group (P<0.05). The serum level of TNF-alpha and
      IFN-gamma of the patients in AA group was significantly higher than those in the
      control group (P<0.05), and the level of sFas in AA group was significantly lower
      than those in the control group (P<0.05). The levels of serum TNF-alpha and IFN
      gamma in the acute group were significantly higher than that in the chronic group
      (P<0.05), and the level of sFas was significantly lower than that in the chronic
      group (P<0.05). The analysis of each index value for predicting the severity of
      AA by ROC showed that the area under curve of CD4+ /CD8+ , TNF-alpha, IFN-gamma
      and sFas for predicting the patients' condition was 0.954, 0.763, 0.853 and
      0.857, respectively. Kaplan-Miere survival curve analysis showed that CD4+ /CD8+
      ratio had a significant effect on progression-free survival (P<0.05), the TNF
      alpha, IFN-gamma and sFas levels had no significant effect on progression-free
      survival (P>0.05). CONCLUSION: The patients with aplastic anemia have
      significantly abnormal T lymphocyte subsets, there is a certain correlation
      between the serum TNF-alpha, IFN-gamma and sFas levels with aplastic anemia, each
      index can reflect the disease severity, and the changes of T lymphocyte subsets
      has important influence on the clinical prognosis of the patients.

PMID- 30295269
TI  - [Oxidative Stress Status and Its Effect on Regulation of Hepcidin in Patients
      with HbHCS].
AB  - OBJECTIVE: To investigate the oxidative stress status and its effects on hepcidin
      in patients with hemoglobin H Constant Spring disease (HbH-CS). METHODS: A total
      of 35 patients were enrolled in the study, including 15 splenectomized cases and
      20 non-splenectomized cases. 20 healthy volunteers were selected as controls.
      Serum superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH),
      oxidized glutathione (GSSG) levels, erythropoietin (EPO), serum free transferrin
      receptor (sFTR), growth differentiation factor 15 (GDF15) as well as the level of
      hepcidin were detected. Correlation analysis and multiple factor regression
      analysis were performed to investigate the factors affecting the iron metabolism
      and erythropoiesis. RESULTS: Compared with healthy control, the SOD and GSH
      levels in patients with HbHCS decreased, while MDA and GSSG levels increased. The
      levels of SOD, MDA, GSG and GSSG were not significantly different between the
      patients with splenectomy and those without splenectomy. Correlation analysis
      showed that inpatients with HbHCS, EPO, sFTR and GDF15 correlated negatively with
      SOD level and positively with MDA level. EPO and sFTR levels negatively
      correlated with Hepcidin. CONCLUSION: Excessive oxidative stress is present in
      patients with HbHCS, and hepcidin is inhibited by the upregulation of EPO and
      sFTR, and hence involved in iron overload in patients.

PMID- 30295270
TI  - [Clinical Significance of Detecting Tissue Factor and Tissue Factor Pathway
      Inhibitor in Thalassemia Patients].
AB  - OBJECTIVE: To investigate the changes of E-selectin, thrombin-antithrombin
      complex(TAT), prothrombin fragment 1+2(F1+2), tissue factor(TF)and tissue factor
      pathway inhibitor(TFPI)before and one year after splenectomy in thalassemia
      patients. METHODS: A total of 30 thalassemia patients undergoing electric
      laparoscopic splenectomy and 30 normal controls(NC) were enrolled in the
      study.Plasma levels of E-selectin, TAT, F1+2, TF and TFPI were detected by enzyme
      linked immuno sorbent assay(ELISA). RESULTS: One year after splenectomy,the
      plasma concentrations of E-selectin, TAT, F1+2, TF, TFPI were significantly
      higher than those in both preoperative and NC groups.Levels of E-selectin, TAT,
      F1+2 before splenectomy were significantly higher than those in NC groups. In
      addition, there was a positive correlation between plasma TF and TFPI level
      before and after splenectomy, and the levels of TF and TFPI positively correlated
      with TAT and F1+2, respectively. CONCLUSION: After splenectomy, the platelet
      count increases, the activity of endothelial cells is injured, the procoagulant
      factor increases, the blood is in procoagulant state, the TF/TFPI shows an
      importent role in the thrombosis of thalassemia patieints after splenectomy and
      may be used to evaluate the prothrombotic state of this diasease.

PMID- 30295271
TI  - [Effects of Synthetic Long-Chain Polyphosphate on Blood Coagulation and Platelet
      Aggregation].
AB  - OBJECTIVE: To investigate the effects of synthetic long-chain polyphosphate on
      blood coagulation and platelet aggregation. METHODS: The effect of artificial
      synthetic long chain poly phosphate on blood coagulation and platelet aggregation
      was detected by coagulation tests, coagulation factor activity detection and
      platelet aggregation test, and its mechanism was explored by ELISA, flow
      cytometry and high content imaging system. RESULTS: The long chain polyphosphates
      prolonged activated partial thromboplastin time, decreased coagulation factor
      FVIII, FIX, FXI and FXII activity, blocked ADP-induced platelet aggregation, and
      decreased the concentration of calcium and TXA2 in platelet. CONCLUSION: The
      synthetic long-chain polyphosphate can inhibit endogenous coagulation and inhibit
      platelet aggregation, which may be related with the inhibition of intracellular
      calcium and TXA2.

PMID- 30295272
TI  - [Monitoring of Coagulation Status and Evaluation of Antiplatelet Aggregation in
      Patients with CHD by Using TEG].
AB  - OBJECTIVE: To evaluate the performance of thromboelastography (TEG) to monitor in
      vivo blood coagulation status and the efficacy of antiplatelet aggregation drugs
      in the patients with coronary heart disease (CHD) after oral anticoagulation.
      METHODS: Seventy one CHD patients were enrolled in CHD group and 380 healthy
      persons with normal TEG were enrolled in the control group. After admission, all
      CHD patients were administrated with routine anti-platelet aggregation drugs at a
      clinically recommended dose. Then, TEG was applied to monitor the basic blood
      coagulation indexes, such as R value, K value, alpha angle, MA value, CI value
      and a series of related indexes on platelet inhibition. RESULTS: Above 80% of the
      basic blood coagulation indexes in TEG were within normal reference range in the
      CHD group. the R value, MA value, alpha angle and CI value in the CHD group were
      not significanly different, from that in the control group, but the K value
      significantly increased (P<0.05). Compared with the control group, relatively
      higher ratio of male was included in the CHD patients at much older age (P<0.05),
      83.1% of the CHD patients achieved significant anti-platelet aggregation effect
      (platelet inhibition rate>50%). Other antiplatelet aggregation indexes, MAADP,
      MAck and MAA suggested a 9.86%, 4.23% and 12.68% risk of thrombogenesis,
      respectively. Among all the related antiplatelet aggregation indexes, MAck showed
      the strongest correlation with age (correlation coefficient, 0.111), and ADP%
      most highly correlated with body mass (correlation coefficient, 0.160).
      CONCLUSION: TEG results can provide valuable coagulation information for
      clinicians, thus certainly guiding in the treatment for CHD patients receiving
      anti-platelet therapy. Moreover, the application of TEG can also provide accurate
      information for further individualized treatment of CHD patients, which would
      funther inprove the safety of anti-thrombotic therapy.

PMID- 30295273
TI  - [Effects of Stored Apheresis Platelet Apoptosis on Aggregation Function].
AB  - OBJECTIVE: To investigate the effects of storage lesion in apheresis platelets on
      platelet apoptosis and the changes of aggregation function, and analyze the
      relationships between the apoptosis and aggregation function. METHODS: Platelet
      samples were collected from 10 healthy donors with O blood group. Firstly, the
      effects of storage lesion in platelets on the platelet apoptosis were detected by
      flow cytometry. Then, using a multiplate analyzer, individual-donor Plt
      aggregation response to stimulation by the agonists ADP, Collagen, TRAP and ASPI
      was examined. Finally, the relationships between its apoptosis and aggregation
      function was analyzed by correlation regression analysis. RESULTS: By flow
      cytometry it was found that with the prolonging of storage time, the apoptosis
      ratio of platelets significantly increased in a time-dependent manner, the
      apoptosis rates of platelets on 2nd, 5th and 8th day were (2.87+/-0.31)%,
      (11.08+/-1.54)% and (27.99+/-2.76)% respectively (P<0.01). Compared with Day 2
      platelets, the d 5 platelets stored for 5 d significantly decrease the
      aggregation response to stimnlation of collagen, TRAP, and ASPI. Compared with
      platelets stored for 5 d, platelets stored for 8 d significantly decreased the
      aggregation response to stimnlation of collagen, TRAP and ASPI (P<0.01). However,
      when stimulated by ADP, the aggregation response was similar among Day 2, Day 5
      and Day 8 platelets. The rate of the aggregation function was also declined
      significantly when stimulated by collagen, TRAP, and ASPI, but not ADP. Further
      regression analysis showed that the aggregation function of apheresis platelet
      negatively correlated with the apoptosis (r=-0.9497, r=-0.9527, r= -0.9707 and r=
      -0.9352 respectively), and the correlation is very strong. CONCLUSION: With the
      prolonging of storage time, the apoptosis ratio in platelets significantly
      increased. The aggregation function also is declined significantly when
      stimulated by collagen, TRAP, and ASPI, but not ADP. The aggregation function of
      apheresis platelets closly correlats with the apoptosis.

PMID- 30295274
TI  - [Impact of JAK2V617F Mutation Burden on Clinial Presentation and Survival in ET
      Patients].
AB  - OBJECTIVE: To better define the effect of JAK2V617F mutant allele burden on
      clinical presentation of patients with essential thrombo cythamia (ET),
      especially thrombosis. METHODS: Two ml of heparin anti-coagulated bone marrow was
      collected from 229 ET cases, who were diagnosed and treated in the First People's
      Hospital of Yunnan Province during 2013.10 to 2016.12. and then the mononuclear
      cells were separated by Red Blood Cell Lysis Buffer, genomic DNA was extracted
      from mononuclear cells by using a commercial DNA isolation kit and amplified by
      allele specific polymerase chain reaction (PCR). According to the size of
      molecular weight, the amplified products were separated by electrophoresis on a
      2% agarose gel to screen the JAK2V617F mutation, then the JAK2V617F mutation
      burden was detected by real-time polymerase chain reaction (RT-PCR) in 120
      patients with JAK2V617F mutation. Meanwhile, these samples were sequenced in
      order to verify the accuracy of the PCR screewing. RESULTS: ET patients with
      thrombotic events had significantly higher JAK2V617F allele burden than those
      without thrombosis (23.2% vs 14.2%) ( P<0.05). Meanwhile, ET patients showed
      increased JAK2V617F allele burden in the group with higher leukocytosis (WBC >
      10*109/L) (P<0.001) and hemoglobin (> 150 g/L) (P<0.05). JAK2V617F mutation
      burden in 17 patients with splenomegaly was higher than that in 45 patients
      without splenomegaly (28.1% vs 11.8%) (P<0.05). but the JAK2V617F mutation burden
      was regatively correlated with platelet count (P<0.05). On the other hand, no
      correlation was found between JAK2V617F mutation burden and sex (P > 0.05).
      Univariate analysis showed that the JAK2V617F allele burden did not affect
      survival. Multivariable analysis showed that prognostic variable including WBC
      counts, hemoglobin level, age, sex, and splenomegaly not affected survival, (P >
      0.05). CONCLUSION: The clinical presentations of ET patients, such as WBC counts,
      hemoglobin level and splenomegaly, are influenced by the JAK2V617F mutation
      burden. ET patients with thrombotic events has significantly higher JAK2V617F
      allele burden than those in ET palients without thrombosis.JAK2V617F mutation
      burden has no relations with sex and age..

PMID- 30295275
TI  - [Role of Th17 Cells, Interleukin-17 and Matrix Metalloproteinase-13 in
      Pathogenesis of Henoch-Schonlein Purpura].
AB  - OBJECTIVE: To explore the immunopathogenesis of Henoch-Schonlein purpara (HSP) by
      detecting the levels of Th17 cells, IL-17 and matrix metallo proteinase-13 (MMP
      13) in peripheral blood and the expression of IL-17 in skin lesions at acate
      phase of HSP. METHODS: Th17 cell ratio in peripheral blood of HSP group and
      healthy control group was defected by flow cytometry, the plasma levels of IL-17
      and MMP-13 in HSP group and healthy control group were defected by ELISA, and
      expression level of IL-17 in skin lesion of HSP group and skin tissue of healthy
      control group was deternined by: immunohistochemistry method. RESULTS: the ratio
      of Th17 cells in periphral blood of HSP group (1.21+/-0.59%) was very signif
      cantly higher than that in peripheral blood of control group (0.71+/-0.26%) (
      t=4.907, P<0.01). The plasma levels of IL-17 and MMP-13 at acute phase of HSP
      were very significantly higher than those in control group (64.58+/-36.21) pg/ml
      vs (26.16+/-14.90) pg/ml and (17.57+/-5.40) pg/ml vs (11.53+/-4.40) pg/ml
      respectively (t=6.183, P<0.01 and t=5.022, P<0.01). The integrool optical density
      of IL-17 in skin lesin tissue of HSP group (7.26+/-2.34) was higher than that in
      control group (4.61+/-1.82) ( t=2.877, P<0.01). CONCLUSION: Th17 cells, IL-17 and
      MMP-13 may be involved in the immunological pathogenesis of HSP.

PMID- 30295276
TI  - [Clinical Efficacy of Autologous Transplantation of Hematopoietic Stem Cells
      Cryopreserved by Ladder-style Freezing from Low Temperature Refrigerator to
      Liquid Nitrogen].
AB  - OBJECTIVE: To investigate the efficacy of hematopoietic stem cells cryopreserved
      by ladder-style freezing from low temperature refrigerator to liquid nitrogen in
      treatment of hematological malignancies, and to analyze the survival condition of
      patients after hematopoietic stem cell transplantation. METHODS: The
      coyoprotectant formed by 3% hydroxyethyl starch, 4% albumin and 5% dimethyl
      sulfoxide (DMSO) was need for cryopreservation of hematopoietic stem cells,which
      were first placed in -800C low temperature refrigerator and then were stored in 
      1960C liquid nitrogen tank. 98 cases of hemafologic malignancies (io cases of
      ALL, 24 cases of AML, L-cases of MM and 53 case of malignant lymphoma) were
      selected from January 2002 to December 2016, and recived transplantatin auto
      hematopoiehc stem cells cryopresorved by above-mentined method. The overall
      survival rate (OS), progression-free survival (PFS) were analyzed statistically.
      RESULTS: One case failed in implantation due to intracranial hemorrhage and the
      other 97 cases all succeeded in hematopoietic reconstitution. The average time
      needed for neutrophil count >=0.5*109/L was 9.24+/-1.89 d, and the average time
      needed for blood platelet >=20*109/L without platelet transfusion for 3 days was
      11.04+/-1.84 d. The median survival time was 47.6 months (1-80 months). The 3 and
      5 year OS rates were (97.2+/-1.9) %, (84.2+/-4.6) % and (77.8+/-5.6) %,
      respectively. 3- and 5-year PFS of patients were (74.4+/-5.1)% and (61.2+/-6.2)%.
      CONCLUSION: ladder-style freezing from low temperature refrigerator to liquid
      nitrogen can reach the same clinical transplantation effect with traditional
      programmed cooling freezing method in autologous hematopoietic stem cells
      transplantation. moreover the incidence of complications after transpeantatim
      does not show increase.

PMID- 30295277
TI  - [Clinical Analysis of Treating EBV Infection Accompanied with GVHD after Allon
      HSCT by EBV-Specific Cytotoxic T Lymphocytes].
AB  - OBJECTIVE: To investigate the efficiency and safety of treating Epstein-Barr
      virus (EBV) infection of acute graft versus host disease (GVHD) after allogeneic
      hematopoietic stem cell transplantation (allo-HSCT) by EBV specific cytotoxic T
      lymphocytes (EBV-CTL). METHODS: The Clinical characteristics, therapeutic
      efficacy and safety of 12 patients with EBV infection treated by EBV-CTL infusion
      after allo-HSCT in Department of Hemahlogy of Aero Space Center Hospital between
      Jan 2015 and May 2017 were analyzed retrospectioely. RESULTS: Our of 12 cases
      received EBV-CTL infusion after transplantation, 9 did not received Rituximab
      therapy due to the active infection, 4 cases including 3 received Ritaximab
      progressed into posttransplantation lymphoroliferetive disease (PTLD). The median
      time of EBV infection was 47 (22-71) days, median time of antivirus therapy
      before tramplantation was 10 (8-33) days, median time of first CTL infusion was
      59(34-86) days after transplatation. The 43 cases-time CTL infusion was performed
      smoothly, no related harmful evnts occoured, no progression of GVHD was observed.
      After the first course of infusion, complete remission (CR), Partial remssion
      (PR) and no remssion (NR) were obtained in 9, 1 and 2 patients respectively, the
      relapse was observed in 4 patients who then received the socond course of
      infusion and all reached CR, the patient in PR did not reathed CR finally and
      died of GVGD at 5 months after transpplantation . Only 1 out of 2 cases of NR
      obtained CR, another 1 still was in NR, and died of transplantation related
      infection at 5 months after transplantation. 4 cases of PTLD were all cared.
      CONCLUSION: Preliminary results of this study suggest that EBV-CTL infusion is
      safe for the EBV infection combined with acute GVHD after all-HSCT. However, a
      further larger scale clinical studies are needed to prove the efficiency.

PMID- 30295278
TI  - [Effect of Shh and BM-MSC Synergism on the Proliferation of Hematopoietic Stem
      Cells].
AB  - OBJECTIVE: To study the effect and mechanism of shh and mesenchymal stem
      cell(MSC)synergism on the proliferation of hematopoietic stem cells in
      noninvasive co-culture system in vitro. METHODS: The mesenchymal stem cells were
      cultured in vitro,CD34+ cells were sorted by mini MACS magnetic bead
      separator,flow cytometry was used to identify the purity of 2 cells. CD34+ cells
      and MSCs were seeded to upper and low of transwell respecibely for non-contact
      coculture,and add exogenous shh protein for intervenece. The number of MSCs and
      HSCs,the total amount of RNA,the expression of ki67 and Tie-2 mRNA of HSC,the
      expression of VEGF and Ang-1 mRNA of MSC were detected for investigating the
      condition of cell proliferation and the expression of angiogenic factors.
      RESULTS: The total number of cells,the total amount of RNA and the relative
      expression of ki67, Tie-2, VEGF and Ang-1 in non-contact co-culture group
      increased and showed the following trends on the 7th day:the above-mentioned
      indexes in group MSC + HSC, group shh + HSC were higher than those in group HSC,
      while those in MSC + shh + HSC Group was higher than those in MSC + HSC and shh +
      HSC group. CONCLUSION: Angiogenic factors help MSC to proliferate HSC and amplify
      the CD34+ hematopoietic stem/progenitor cells by shh and MSC synergism in vitro
      coculture system which may be related with angiogenic factors.

PMID- 30295279
TI  - [Effects of Exosomes Derived from miR-486 Gene Modified Umbilical Cord
      Mesenchymal Stem Cells on Biological Characteristics of Rat Cardiomyocytes].
AB  - OBJECTIVE: To investigate the effects of exosomes derived from miR-486 gene
      modified umbilical cord mesenchymal stem cells (UC-MSCs) on biological
      characteristics of rat cardiomyocytes. METHODS: The human umbilical cord
      mesenchymal stem cells (UC-MSCs) were isolated and cultured, then the
      immunophenotypes and ability of osteogenic and adipogenic differentiation of UC
      MSC were identified. The structure of exosomes was observed by electron
      microscopy; the effect of exosomes on cell migration was detected by transwell
      cell migration test; the miR-486 high expression of UC-MSC was mediated by using
      recombinant adenovirus vector, moreover the UC-MSC with high expression of miR
      486 were identified by qPT-PCR. The exosomes were isolated from cell culture
      supernatant by ultracentrifugation and the miR-486 expression level of UC MSC
      exosomes was detected by qRT-PCR. The effect of exosomes on the proliferation of
      cardiomyocytes was evaluated by Dye670 marking. The H2O2-induced cardiomyocyte
      apoptosis model was established, and the effect of exosomes on apoptosis of
      cardiomyocytes was detected by flow cytometry with Annexin V/PI double staining.
      RESULTS: The exosomes derived from UC-MSCs had the diameter between 40-100 nm and
      double membrane stracture. The recombinant adenovirus could effectively mediate
      the expression of miR-486 in UC-MSC, and the expression level of miR-486 in
      exosomes of miR-486-modified UC-MSC significantly increased. The exosomes with
      miR-486 high expression possessed the pro-proliferation and pro-migration effects
      on cardiomyocytes, moreover the preventive effect on apoptosis of cardiomyocytes.
      CONCLUSION: The exosomes derived from UC-MSC and accompamied by high expression
      of miR-486 can promote the proliferation and migration of cardio myocytes, yet
      can prevent the apoptosis of cardiomyocytes.

PMID- 30295280
TI  - [Mesenchymal Stem Cells Stimulated by Growth Factors Release Exosomes with Potent
      Proangiogenic Activity].
AB  - OBJECTIVE: To explore the proangiogenic activity of exsomes released by human
      umbilical cord mesenchymal stem cells (MSCs) stimulated by erythropoietin and
      platelet-derived growth factor BB (PDGF-BB). METHODS: Human umbilical cord
      derived MSCs were seeded and maintained in culture overnight. The media were then
      replaced by alpha-MEM containing EPO (1 U/ml) and/or PDGF-BB (50 ng/ml), and the
      culture was maintained for 72 hours. The exosomes from the culture supernatants
      were isolated with a routine ultra-catrifagation method. Flow cytometric analysis
      was performed to identify the origin of the exosomes, and their morphological
      features were observed by using a transmission electron microscopy. The exosomes
      were added at a concentration of 10 ug/ml into the culture system of human
      umbilical cord vein endothelial cells. MTT assay was used to evaluate the
      proliferative status. The Matrigel assay was used to observe the formation of net
      work structures which were calculated after culture for 12 hours. RESULTS: Flow
      cytometric analysis showed that microparticles released by human umbilical cord
      MSCs expressed CD9, CD63 and CD81, which was in accordance with the surface
      molecular features of exosomes. Under an electron microscope, the exosomes took
      the featured cystic shape. The protein contents of exosomes released by
      untreated, EPO-stimulated, PDGF-BB-stimulated and EPO plus PDGF-BB stimulated
      MSCs (108 cells) were 256+/-124 ug, 1021+/-392 ug, 830+/-265 ug and 2207+/-733
      ug, respectively. The results revealed that MSCs treated by EPO and PDGF-BB
      released significantly higher amounts of exosomes (P<0.01). MTT assay proved that
      the exosomes from EPO and PDGF-BB treated MSCs had more potent proliferation
      promoting activity on human umbilical cord vein endothelial cells than those from
      untreated MSCs. The Matrigel assay showed that the numbers of capillary-like
      structures in untreated, EPO-, PDGF-BB and EPO plus PDGF-BB-treated groups were
      2.6+/-0.84, 4.6+/-1.57, 4.2+/-0.78 and 6.3+/-1.34 per high power objective.
      Treatment with EPO or PDGF-BB dramatically enhanced the numbers of capillary liue
      structure, compared with that of untreated group (P<0.01) and those in EPO and
      PDGF-BB combination group was significantly greater than those of EPO or PDGF-BB
      group (P<0.01). CONCLUSION: EPO and PDGF-BB can stimulate MSCs to release
      exosomes with more potent proangiogenic activity.

PMID- 30295281
TI  - [Effect of Lentiviral Vector-Mediated CXCR4 Gene Overexpression on Mesenchymal
      Stem Cell Homing Capacity].
AB  - OBJECTIVE: To explore the effects of lentiviral-mediated CXC chemokine receptor
      4(CXCR-4)gene over-expression on the homing capacity of mesenchymal stem
      cells(MSC)in vivo. METHODS: The MSC overexpressing CXCR-4 were constructed by
      using the lentiviral vector-mediated mouse MSC overexpressing the CXCR-4 gene.
      The BALB/c mice were divided into 3 group: simple radiation group(TBI)in which
      mice exposed to total body irradiation, then were infused with normal saline;
      EGFP-MSC group in which mice were infused with MSC(5*105)transducted by EGFP via
      tail vein after TBI; and CXCR-4-MSC group in which mice were infused with MSC
      (5*105) simultaneously carraying EGFP and CXCR-4 gene via tail vein after TBI.
      The mice were sacrified at 24 hours after infusion, the frozen sections were
      prepared to detect the distribution of infused MSC. Furthermore, the numbers of
      MSC homing into spleen and bone marrow was detected by flow cytometry, and the
      level of stromal cell-derived factor-1(SDF-1) was detected by ELISA. RESULTS: The
      frozen section showed that the CXCR-4 over-expression could significantly enhance
      the efficacy of MSC homing into lung, liver and spleen; the flow cytonetry
      detection slowed that the number of over-expressed CXCR-4 MSC homing into spleen
      and bone matrow was sigmificantly higher than that in EGFP-MSC group(P<0.05), the
      ELISA showed that the SDF-1 level in peripheral blood and bone marrow after 24
      hours of irradiation significantly incrtaoed (P<0.05), moreover, the SDF-1 level
      increase was associcted with horming efficacy of MSC with CXCR-4 overexpression.
      CONCLUSION: overexpression CXCR-4 gene mediated by lentiviral vector can prmote
      the efficacy of MSC homing into spleen and bone marrow.

PMID- 30295282
TI  - [Diagnostic Values of Procalcitonin, C-reactive Protein and Interleukin-6 in
      Hematological Diseases with Bacterial Infection].
AB  - OBJECTIVE: To evaluate the diagnostic values of procalcitonin(PCT), C-reactive
      protein(CRP) and interleukin-6 (IL-6) in patients suffered from hematological
      diseases with bacterial infection, and to provide further evidence for clinical
      application. METHODS: A total of 3631 blood cultures, serum levels of PCT and CRP
      and IL-6 (n=1587) from the inpatients from 2014-01-02 to 2018-01-27 were
      retrospectively analyzed. The patients were divided into positive (n=208) and
      negative blood culture (n=3423) groups. Positive blood culture group were
      redivided into gram-positive (n=34) and gram-negative (n=174) subgroups. The
      values CRP, PCT and IL-6 were compared respectively in these groups. The data
      were analyzed by using R 3.4.4 language. RESULTS: The medians of PCT values in
      positive and negative blood culture groups were 0.41(0.04-103.34) MUg/L and
      0.20(0.02-200) MUg/L(P<0.001) respectively. The medians of CRP values in positive
      and negative blood culture groups were 9.49(0.1-370) mg/dl and 5.42(0-370) mg/dl
      (P<0.001) respectively. The medians of IL-6 values in positive and negative blood
      culture groups were 186.1(2.0-5000, n=91) pg/ml and 52.65(1.5-5000, n=1496) pg/ml
      (P<0.001). The medians of PCT values in gram-positive and gram-negative groups
      were 0.20(0.05-93.83) MUg/L and 0.58(0.04-103.34) MUg/L (P=0.006) respectively.
      The medians of CRP value in gram-positive and gram-negative groups were 9.19(0.1
      35.3)mg/dL and 9.49(0.1-370) mg/dl (P=0.300) respectively. The medians of IL-6
      values in gram-positive and gram-negative groups were 83.01(5.61-1500, n=12)
      pg/ml and 208(2.0-5000, n=79) pg/ml (P=0.357). CONCLUSION: The PCT, CRP and IL-6
      levels were significantly higher in the positive blood culture group than those
      in the negative blood culture group, so provide the effective early diagnostic
      markers for blood culture. PCT levels in gram-positive group were significantly
      higher than that in gram-negative groups, contributing to distinguish between the
      2 groups.

PMID- 30295283
TI  - [Coagulation Properties for Whole Blood Stored at 4C].
AB  - OBJECTIVE: To study the coagulation properties the refrigerated whole blood
      stored at 4C. METHODS: Ten units of whole blood were obtained from healthy
      volunteer donors and stored at 4+/-2C for 21 days. Samples were collected on the
      day after donation and on days 2, 4, 6, 8, 10, 14 and 21 for delection including
      complete blood count, electrolyte, APTT, PT, Fg, blood coagulation factors, and
      thromboelastography(TEG). RESULTS: The levels of Hb, WBC, Plt, sodium and
      potassium in each sample accorded with standard of storing whole blood. The level
      of Hb, WBC, Plt and Na+ decreased along with prolonging of storage time, while
      the K+ level increased along with prolonging of stored time, APTT and PT
      prolonged along with prolonging of thored time, PT>17 min at d 21, the Fg level
      change was no-obvious, The level of factor V and VIII decreased more than 50 % of
      baseline on d 6 and 4 respectively; the levels of factor II, VII, IX, X, XI, XII
      showed decreasing trend, but their levels were less than 40 % of baseline values
      at d 21. TEG test showed that no abnormalily of R value was found, the abnormal
      valnes of K and Angle were observed at d 21, the abnormal value of MA was
      observed at d 14. CONCLUSION: The whole blood stored for 10 days possesses normal
      coagulation function showing important significance for treatment of hemorrhage
      from war injury and surgical openation of heart and chest.

PMID- 30295284
TI  - [A Preliminary Study on the Expression of CD160 on NK Cells and Its Mechanism of
      Mediating NK Killing Effect].
AB  - OBJECTIVE: To investigate the expression of CD160 on the surface of human natural
      killer (NK) cells and its possible relationship with hematological malignancies.
      METHODS: CD160 expression on human leukemia cell line NK92 cells was confirmed by
      reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The
      proliferation characteristics and cell surface markers of this cell line were
      determined. Cytotoxicity of NK92 against 2 human myeloid leukemia cell lines,
      K562 and THP-1 was analyzed ex vivo. CD160 blocking antibody CL1-R2 was employed
      to clarify its role in NK cell mediated cytolysis. Then, the expression of CD160
      on NK cells in peripheral blood from various patients with hematological
      malignancies were measured by flow cytometry. RESULTS: The mRNA and protein
      levels of CD160 expressions on NK92 cells were confirmed by RT-PCR and Western
      blot, respectively. The flow cytometry results demonstrated that the strong
      positive expression of CD160 could be detected on the NK92 cell surface. NK92
      could effectively kill K562 and THP-1 cells, while the cytolysis effect was
      abrogated in the presence of CD160 blocking antibody CL1-R2. The high levels of
      HVEM were expressed on both target cells, but the HLA class I molecules were
      absent on K562. The expression of CD160 on CD3-CD56+ NK cells in peripheral blood
      from patients with acute myeloid leukemia (AML), chronic lymphocytic leukemia
      (CLL) and allogeneic hematopoietic stem cell transplantation (allo-HSCT)
      recipients was significant lower than that in the normal controls (P<0.05).
      CONCLUSION: The cytolysis function of human NK cells is mediated partially by
      CD160 molecule. The decrease of CD160 expression on NK cells from patients with
      various hematological malignancies implies that down-regulation of CD160
      expression may be a novel mechanism of tumor immune escape.

PMID- 30295285
TI  - [Research Advances on BK Virus Associated Hemorrhagic Cystitis after HSCT
      Review].
AB  - BK virus(BKV)associated hemorrhagic cystitis is one of the most common
      complications after hematopoietic stem cell transplantation(HSCT), which can
      increase the suffering, become time consuming and even life threatening. However,
      BKV infection has not attracted enough attention in clinical practice. Accurate
      BKV monitoring and effective clinical treatments are still in urgent need. In
      recent years, BKV-DNA monitoring has shown a significant clinical value in BKV
      associated hemorrhagic cystitis after HSCT. As for clinical treatments,
      traditional antivirus agent cidofovir is still to show promising effects, in the
      meantime, the virus-specific lymphocytes and other new therapies are continuously
      appearing. Here, the most recent advances on pathogenesis, treatment, virus
      monstoring and so on for BKV associated hemorrhagic cystitis after HSCT are
      reviwed.

PMID- 30295286
TI  - [Research Progress in Acute Hemolysis and Safe Blood Transfusion of Glucose-6
      Phosphate Dehydrogenase Deficiency-Review].
AB  - Glucose-6-phosphate dehydrogenase deficiency (G6PD) is one of hereditary diseases
      sariously influencing the human health. G6PD is characterized by wide
      distribution, high incidence, inducing the hemolysis, complex mechanism of
      hemolysis and common occurence in children and so on. The blood transfusion is
      most effective method for acute ouset of hemolysis, but the risk is more high,
      thereby it is necessary to guarante the safety of blood transfusion. In addition
      of the routine managementin blood transfusion and standard procedures, the basic
      rules and indicators of blood transfusion must be grasped, the blood preparations
      should be known well, the blood protection must be strengthened, and the measures
      of personalized psychologic interference must be drawn up carnestly and performed
      strictily so as to improve the therapeutic efficacy and safe of blood
      transfusion. Through the promotion and development of social pubbicity, elucation
      activities, preventive and control measures and medical levels, many patients
      have been freed from healthy problems as soon as possible. In this review, the
      research progress on acute hemolysis and safe blood transfusion in G6PD are
      summarized.

PMID- 30295287
TI  - [Mechanism and Its Countermeasure of Hypomethylating Agent Resistance in Patients
      with Myelodysplastic Syndrome--Review].
AB  - Hypomethylating agents(HMA) currently are widely used in the treatment of
      myelodysplastic syndromes (MDS), provide a significant improvement in the
      treatment of MDS. However, resistance to HMA is an almost universal phenomenon.
      This review was focused on immune effects related to DNA methylation, and to
      explore the mechanism underlying HMA resistance involved in immune checkpoint
      pathways. However, the optimal role of checkpoint blockade therapy (CBT) and
      immune checkpoint pathways remain in HMA failure questionable. The better
      understanding of immune checkpoint pathways in resistance of HMA offers a
      compelling rationale to introduce CBT in patients as a novel treatment option.
      CBT is an established strategy in solid tumors with potential as an adjunctive
      therapy in hematologic malignancies, therefore, may alter the treatment landscape
      in MDS. The suitability and effectiveness of combining HMA with CBT need to be
      confirmed by the results of ongoing clinical trials, so as to find novel
      strategies to improve outcome after failure of HMA.

PMID- 30295288
TI  - [Research Progress on Ph-like Acute Lymphoblastic Leukemia--Review].
AB  - Ph-like acute lymphoblastic leukemia (ALL) is a high-risk subtype of precursor B
      cell acute lymphoblastic leukemia (BCP-ALL) with a gene expression profile and a
      high frequency of IKZF1 gene alteration similar to that of Ph-positive ALL, which
      is a clinically and biologically heterogeneous subtype of BCP-ALL. The prognosis
      correlats negatively with age increasing. The incidence of this "Ph-like" subtype
      may be higher in young adults. Ph-like ALL is characterized by genetic
      alterations that activate cytokine receptor genes and kinase signaling pathways.
      Prospective studies are needed to determine if incorporation of tyrosine kinase
      inhibitor-targeting kinase alterations into intensive chemotherapy regimens will
      improve outcome of patients with Ph-like ALL. The research progress of Ph-like
      ALL is summarised in this review, including epidemiology, genetic alterations and
      treatment..

PMID- 30295290
TI  - Intravascular Lithotripsy to Treat a Severely Under-Expanded Coronary Stent.

PMID- 30295291
TI  - Twelve-month results of the Italian registry on protected CAS with the mesh
      covered CGuard stent: the IRON-Guard study.

PMID- 30295292
TI  - Long Term Follow-up of an Extreme Kinking of Right Coronary Artery Stenosis
      Treated With Bioresorbable Vascular Scaffold.

PMID- 30295289
TI  - Replication Study: Intestinal inflammation targets cancer-inducing activity of
      the microbiota.
AB  - As part of the Reproducibility Project: Cancer Biology we published a Registered
      Report (Eaton et al., 2015) that described how we intended to replicate selected
      experiments from the paper "Intestinal Inflammation Targets Cancer-Inducing
      Activity of the Microbiota" (Arthur et al., 2012). Here we report the results. We
      observed no impact on bacterial growth or colonization capacity when the
      polyketide synthase (pks) genotoxic island was deleted from E. coli NC101,
      similar to the original study (Supplementary Figure 7; Arthur et al., 2012).
      However, for the experiment that compared inflammation, invasion, and neoplasia
      in azoxymethane (AOM)-treated interleukin-10-deficient mice mono-associated with
      NC101 or NC101[Formula: see text] pks the experimental timing of the replication
      attempt was longer than that of the original study. This difference was because
      in the original study the methodology was not clearly stated and likely led to
      the increased mortality and severity of inflammation observed in this replication
      attempt. Additionally, early death occurred during AOM treatment with higher
      mortality observed in NC101[Formula: see text] pks mono-associated mice compared
      to NC101, which was in the same direction, but more severe than the original
      study (Suppleme1ntal Figure 10; Arthur et al., 2012). A meta-analysis suggests
      that mice mono-associated with NC101[Formula: see text] pks have higher mortality
      compared to NC101. While these data were unable to address whether, under the
      conditions of the original study, NC101 and NC101[Formula: see text] pks differ
      in inflammation, invasion, and neoplasia this replication attempt demonstrates
      that clear description of experimental methods is essential to ensure accurate
      reproduction of experimental studies.

PMID- 30295293
TI  - Propensity-Matched Comparison of Vascular Closure Devices after Transcatheter
      Aortic Valve Replacement using MANTA versus ProGlide.
AB  - AIMS: Vascular and bleeding complications increase morbidity and mortality in
      transcatheter aortic valve replacement (TAVR). However, data regarding the
      efficacy and safety of the percutaneous vascular closure device, MANTA is scarce.
      METHODS AND RESULTS: We performed a retrospective, propensity score-matched study
      to compare vascular and bleeding complications in 325 consecutive patients who
      underwent TAVR using MANTA and ProGlide. The 1:1 propensity score-matching
      resulted in 111 matched pairs. For MANTA- versus ProGlide-treated patients, all
      cause mortality (0% vs. 4%, p=0.02), vascular complications (14% vs. 21%,
      p=0.21), and bleeding complications (18% vs. 33%, p=0.01) were observed. Access
      site vascular injury was significantly less frequent in patients who received
      MANTA versus ProGlide (8% vs. 17%, p=0.04). MANTA presented significantly lower
      hemoglobin decrease (16.4 vs. 20.0 g/l, p=0.04) and shorter hospital stay after
      TAVR (3.3 vs. 5.8 days, p=0.02). It also predicted fewer bleeding complications
      (OR: 0.44; 95% CI: 0.23 - 0.83; p=0.01). Moreover, significant decreases of all
      endpoints were not seen across the procedure date tertiles in the MANTA group.
      CONCLUSIONS: MANTA resulted in a significantly lower complication rate,
      especially for bleeding, than did ProGlide despite the operators' inexperience in
      the use of MANTA.

PMID- 30295294
TI  - Plug based closure in completely percutaneous right-sided transaxillary
      transcatheter aortic valve implantation.

PMID- 30295295
TI  - Interventional femoral "cross-over" bypass for peripheral ischemia under
      cardiocirculatory support with Impella CP(r).

PMID- 30295297
TI  - A near-infrared xanthene fluorescence probe for monitoring peroxynitrite in
      living cells and mouse inflammation model.
AB  - Peroxynitrite (ONOO-) plays important roles in the regulation of many
      physiological and pathological processes, and an increase in its levels is
      related to numerous diseases. Thus, accurate detection of ONOO- in physiological
      conditions is imperative for elucidating its functions. However, studies on high
      signal-to-noise-ratio (SNR) fluorescence imaging of ONOO-in vivo for its
      detection are currently lacking. Thus, a novel NIR xanthene fluorescence probe
      (NOF2) for the endogenous detection of ONOO- is designed and synthesized. The
      fluorescence of the NOF2 probe is pre-quenched by the hydroxyl protection group
      of diphenyl phosphinate. Additionally, the NOF2 probe exhibits good selectivity
      and sensitivity for ONOO- with a low detection limit of 0.40 MUM. Importantly,
      the NOF2 probe displays good performances for the detection of endogenous ONOO-
      not only in living cells but also in a mouse inflammation model. This
      demonstrates its great potential for applications involving the detection of ONOO
      both in vitro and in vivo to explore the roles of ONOO- in different
      physiological systems.

PMID- 30295296
TI  - Twenty Minute Moderate-Intensity Post-Dinner Exercise Reduces the Postprandial
      Glucose Response in Chinese Patients with Type 2 Diabetes.
AB  - BACKGROUND Postprandial hyperglycemia and glycemic fluctuations are significant
      cardiovascular disease risk factors for patients with type 2 diabetes. We
      investigated the effects of a single session of post-dinner moderate-intensity
      exercise on the postprandial glycemic response compared with a non-exercise
      condition in a study population of Chinese patients with type 2 diabetes.
      MATERIAL AND METHODS This randomized crossover self-controlled pilot study
      involved 29 patients with type 2 diabetes who participated in post-dinner
      exercise days using non-exercise days as a control. The interstitial glucose
      level was monitored using a continuous glucose monitoring system, with a
      standardized diet and medication. For the non-exercise control days, patients
      pursued normal daily activities but refrained from unusual strenuous physical
      activity. On the exercise days, participants walked on a treadmill for 20 minutes
      after dinner, with a heart rate reserve of 40%. RESULTS Post-dinner moderate
      intensity exercise reduced the 2-hour postprandial glucose spike, mean glucose
      level, and peak glucose level compared to the control condition. The cumulative
      glucose total area under the curve during 1-hour post-exercise was lower with
      exercise than under the control condition. The 12-hour standard deviation of
      blood glucose and the coefficient variation of glucose were significantly lower
      in the with exercise day compared to the control day, although the 12-hour mean
      amplitude of glycemic fluctuations did not reach statistical significance. No
      nocturnal hypoglycemia subsequently occurred on the exercise day. CONCLUSIONS A
      short session of moderate-intensity post-dinner exercise can improve postprandial
      hyperglycemia and glycemic excursions in Chinese patients with type 2 diabetes,
      with no potential hypoglycemia risk at a later period.

PMID- 30295298
TI  - All inorganic coordination polymers have been made possible with the m
      carboranylphosphinate ligand.
AB  - New examples of 1D coordination polymers (CPs) and complexes containing the
      purely inorganic carboranylphosphinate ligand [1-OPH(O)-1,7-closo-C2B10H11]- are
      reported. The reaction of Na[1-OPH(O)-1,7-closo-C2B10H11] salt with MCl2 (M = Mn,
      Co, Ni, Cu, Zn and Cd) in MeOH or EtOH leads to compounds 1-8. All compounds have
      been exhaustively characterized by analytical and spectroscopic techniques. X-ray
      analysis and spectroscopy characterization revealed the differences between the
      isolated compounds: 1D polymeric chains (CPs) with carboranylphosphinate ligand
      bridges have been obtained with MnII, CdII or ZnII centres, whereas compounds
      with low nuclearity have been isolated with CuII, CoII and NiII. No polymeric
      structures were obtained in the CoII and NiII complexes due to the higher
      affinity of these metals for water than that for the m-carboranylphosphinate and
      accordingly, these complexes generate supramolecular hydrophobic/hydrophilic
      structures. The reactivity of manganese polymer 1 with water leads to the
      breakage of the polymer with the formation of a new mononuclear compound 2, and
      that in methanol leads back to the initial polymer 1. However, the reactivity of
      polymer 1 with 2,2'-bpy maintains the core present in the initial polymer,
      leading to the CP 3, which in methanol/water medium produces species of lower
      nuclearity. The magnetic properties of the compounds studied show weak
      antiferromagnetic coupling.

PMID- 30295299
TI  - Water stable oxalate-based coordination polymers with in situ generated cyclic
      dipeptides showing high proton conductivity.
AB  - Presented here are two water stable oxalate-based coordination polymers with in
      situ generated cyclic dipeptides, namely, (C12H16N6O2)[Zn2(C2O4)3] (SCU-63) and
      Mn(C2O4)(C12H14N6O2) (SCU-66). SCU-63 has a honeycomb-like layer intercalated
      with protonated cyclic dipeptide cations. SCU-66 has a diamondoid framework
      containing cyclic dipeptide ligands. The two compounds show high proton
      conductivity on the order of 10-3 S cm-1 at 85  degrees C under 98% relative
      humidity.

PMID- 30295300
TI  - Engineered basement membranes: from in vivo considerations to cell-based assays.
AB  - Improvements in the physiological relevance of cell-based assays have been
      enabled by the development of various interdisciplinary methods. However, due to
      their complexity, in vivo structures such as basement membranes (BMs), which
      regulate the phenotype of adherent cells, are still difficult to mimic in vitro.
      The reconstruction of a physiologically relevant BM is crucially important to
      develop cell-based assays with the capacity for drug screening and disease
      modelling. Here, we review the biophysical and biochemical properties of BMs in
      vivo and their interactions with neighbouring cells. We discuss the current
      methods used to mimic BM functions in cell-based assays according to the type of
      targeted applications. In doing so, we examine the advantages and limitations of
      each method as well as exploring approaches to improve the physiological
      relevance of engineered or cell-derived BMs in vitro.

PMID- 30295301
TI  - Spiers Memorial Lecture. Introductory lecture: quantum dynamics of chemical
      reactions.
AB  - This Spiers Memorial Lecture discusses quantum effects that can be calculated and
      observed in the chemical reactions of small molecules. This includes quantum
      reactive scattering resonances, vibrational and rotational state effects, and
      quantum tunnelling in chemical reactions. Both experimental and theoretical
      advances are reviewed. Of particular emphasis is a description of the development
      of reduced dimensional theories which can highlight chemical reactions that are
      likely to be of interest for more accurate quantum reactive scattering studies
      and new experiments. Furthermore, the reduced dimensional models allow for the
      development and testing of computationally inexpensive procedures that enable
      calculations to be performed on quantum effects in reactions of larger polyatomic
      molecules.

PMID- 30295302
TI  - Analysis of soluble or titanium dioxide derived titanium levels in human whole
      blood: consensus from an inter-laboratory comparison.
AB  - Exposure to titanium (Ti), via the ingestion of pigment grade Ti dioxide (TiO2),
      is commonplace for westernised populations. It may also occur as a consequence of
      metal ion leaching in subjects bearing Ti-containing implants. Accurate exposure
      analysis requires fit-for-purpose analytical methodology, especially for true
      measures of baseline levels. Inductively coupled plasma (ICP) techniques are,
      mainly, now used for bio-analysis of Ti. Since whole blood reference materials,
      certified for natural low levels of Ti, are not currently available, we undertook
      an inter-laboratory comparison of pooled human blood from fasted volunteers +/
      low level (+~2.5 MUg L-1) or high level (+10-20 MUg L-1) spikes of soluble Ti or
      TiO2 particles. Seven established laboratories were enrolled to analyse the
      samples using ICP based techniques, which included at least one of ICP optical
      emission spectrometry (ICP-OES), high resolution ICP mass spectrometry (HR-ICP
      MS), triple quadrupole ICP-MS (ICP-MS/MS) or single quadrupole ICP-MS (SQ-ICP
      MS). Five laboratories diluted the blood for analysis whilst two performed acid
      digestion. Overall, we showed that the laboratories could, mostly, quantitatively
      detect modest levels of spiked Ti in blood. Markedly varying levels of Ti,
      however, were reported for the same baseline pooled sample (0.4-24.6 MUg L-1)
      and, in this study, specificity was poor for SQ-ICP-MS. Digestion of samples
      caused sample contamination compromising limits of detection and accuracy, whilst
      simple dilution had no such problem, and remained linear in response for spikes
      with ionic and TiO2 particles. We conclude that measuring baseline levels of Ti
      in whole blood is challenging but should be readily achievable down to 0.5-1.5
      MUg L-1, if sample preparation avoids contamination and instrument techniques are
      used that negate polyatomic or isobaric interferences from the sample matrix. We
      also remind those relying upon Ti bio-analytical data for their experimental
      outcomes that (a) spiking and recovery experiments provide information only on
      linearity of detection but not at all on accuracy as this will not detect
      constant positive errors and that (b) biological standard materials for Ti
      generally contain high levels of the analyte and tend to mask baseline analytical
      errors. Caution may be required in interpreting the findings of some published
      Ti/TiO2 bio-exposure studies.

PMID- 30295303
TI  - A novel and accurate microfluidic assay of CD62L in bladder cancer serum samples.
AB  - We report a low-cost, sensitive, bead-based electrochemical immunoarray for
      soluble L-selectin (or CD62L protein), a potential biomarker for staging bladder
      cancer. We used a semi-automated modular microfluidic array with online antigen
      capture on superparamagnetic beads, which were subsequently delivered to a
      detection chamber housing multiple sensors. The assay was designed to accurately
      detect CD62L in diluted serum with a limit of detection (LOD) of 0.25 ng mL-1 and
      a dynamic range of 0.25-100 ng mL-1. The microfluidic array gave significantly
      better accuracy and higher sensitivity than a standard ELISA kit, which was shown
      to be subject to significant systematic error at high and low concentration
      ranges. 31 serum samples from patients with varying grades of bladder cancer and
      cancer-free controls were analyzed by the immunoarray and ELISA, and the CD62L
      levels correlated. This work establishes a new accurate assay for determining
      CD62L levels and highlights the potential of this protein as a biomarker for
      detecting locoregional progression of bladder cancer.

PMID- 30295304
TI  - The eta1-H-CHg agostic interactions in the mercury complexes of N-confused
      porphyrin.
AB  - Six four-coordinated complexes of the chemical formulae [Hg(2-N CH2COOCH2CH3-21-H
      NCTPP)X] with X = Cl (5), Br (6), I (7), [Hg(2-NCH3-21-H-NCTPP)Cl] (4) and [Hg(2
      NCH2COOCH2C6H5-21-H-NCTPP)X] with X = Cl (8), I (9) are synthesized and
      structurally determined. The bond path for the weak eta1-H(17)-C(17)Hg agostic
      interactions between the Hg center and H(17) in complexes 4-9 was a through-space
      interaction from Hg to agostic carbon [C(17)] followed by a through-bond
      interaction from C(17) to an agostic proton [H(17)]. The magnitude of J[Hg-H(17)]
      [or the agostic upfield shift Deltadeltaago of the C(17)] for these complexes
      increases as the halide ligand varies from iodide to chloride, ranging from 33.2
      Hz (or 14.3 ppm) for I- to 36 Hz (or 15.8 ppm) for Br- and 36.9 Hz (or 16.0 ppm)
      for Cl-. The plot of J[Hg-H(17)] for the agostic proton H(17) versus
      |Deltadeltaago| for the agostic carbon atom C(17) in compounds 3-9 was linearly
      expressed as J[Hg-H(17)] = 2.29 |Deltadeltaago| + 0.13.

PMID- 30295305
TI  - Sensitive fluorescence detection of heparin based on self-assembly of mesoporous
      silica nanoparticle-gold nanoclusters with emission enhancement characteristics.
AB  - Heparin (Hep) is widely used as a major anticoagulant in surgery. Simple and
      sensitive methods capable of quantitative detection of Hep are desired for better
      regulating its clinical use. Herein, a novel nanoassembly of amino-functionalized
      mesoporous silica nanoparticle-gold nanoclusters (MSN-AuNCs) with remarkable
      emission enhancement characteristics for sensitive fluorescence detection of Hep
      is developed. The electrostatic interaction between the positively charged amino
      functionalized MSNs and the AuNC-stabilizing surface ligands triggers the self
      assembly of MSN-AuNC nanocomposites which exhibit more than 5-fold fluorescence
      emission enhancement. However, the presence of negatively charged Hep inhibits
      the emission enhancement phenomenon due to the effective wrapping of Hep on the
      surface of MSNs, which blocks the interaction between AuNCs and MSNs. Benefitting
      from the remarkable emission enhancement and the competing binding of Hep, facile
      and ultrasensitive detection of Hep can be realized with a detection limit as low
      as 2 nM. Moreover, the successful application of the proposed method for
      detection of Hep in human serum samples shows promise for clinical applications.

PMID- 30295307
TI  - Chemical modification of enveloped viruses for biomedical applications.
AB  - The unique characteristics of enveloped viruses including nanometer size,
      consistent morphology, narrow size distribution, versatile functionality and
      biocompatibility have attracted attention from scientists to develop enveloped
      viruses for biomedical applications. The biomedical applications of the viral
      based nanoparticles include vaccine development, imaging and targeted drug
      delivery. The modification of the structural elements of enveloped viruses is
      necessary for the desired functions. Here, we review the chemical approaches that
      have been utilized to develop bionanomaterials based on enveloped viruses for
      biomedical applications. We first provide an overview of the structures of
      enveloped viruses which are composed of nucleic acids, structural and functional
      proteins, glycan residues and lipid envelope. The methods for modification,
      including direct conjugation, metabolic incorporation of functional groups and
      peptide tag insertion, are described based on the biomolecular types of viral
      components. Layer-by-layer technology is also included in this review to
      illustrate the non-covalent modification of enveloped viruses. Then, we further
      elaborate the applications of chemically-modified enveloped viruses, virus-like
      particles and viral subcomponents in biomedical research.

PMID- 30295310
TI  - Tender coconut water attenuates heat stress-induced testicular damage through
      modulation of the NF-kappaB and Nrf2 pathways.
AB  - Tender coconut water (TCW), a well-known plant beverage, has been used as a
      stress-relieving traditional medicine since ancient times. It is also used to
      treat various ailments of disease, including hepatic disorders, renal disorders,
      gastric disorders and reproductive disorders. However, the reasons for its
      effectiveness as a natural antioxidant as well as its testicular protective
      effects against whole body heat stress (HS)-induced oxidative imbalance remain to
      be revealed. The present study aimed to elucidate the protective efficacy of TCW
      on HS-induced testicular damage in a murine system and to explore the possible
      mechanism of action. Standardized liquid chromatography-mass spectrometry (LC-MS)
      was used to detect the presence of active components in TCW. Male Wistar rats
      were exposed to acute HS with or without TCW treatment to evaluate the degree of
      testicular damage, which was monitored through histological as well as
      biochemical analysis. Assessment of endogenous antioxidant response and the
      modulation of signaling pathways associated with inflammation were also subjected
      to immunofluorescence and flow cytometric evaluation. Acute hyperthermia caused
      an elevation of excess generation of oxygen radicals following the suppression of
      antioxidant capacity and augmentation of lipid peroxidation in murine testicles,
      which was restored by treatment with TCW. The results also demonstrated marked
      phosphorylation of IKKalpha/beta and IkappaBalpha following the activation of NF
      kappaB-guided pro-inflammation upon HS. TCW treatment reversed the HS-induced
      proinflammatory state through activation of the Nrf2-assisted antioxidant
      response, which restored the testicular damage. TCW provided competent scientific
      evidence to substantiate the claims for its use in the treatment of HS-induced
      inflammation and inflammation-mediated testicular damage.

PMID- 30295311
TI  - Determination of nitrite ions in environment analysis with a paper-based
      microfluidic device.
AB  - A new microfluidic paper-based analytical device, a (Ag-MUPAD)-based
      chemiresistor composed of silver ink, has been developed for the selective,
      sensitive, and quantitative determination of nitrite ions in environmental
      analysis. The silver ink acts as an efficient transducer in terms of resistance
      changes due to nitrite initiating a diazo reaction and further reacting with the
      ink. The silver ink is synthesized onto the MUPADs by pulsed light sintering from
      silver nanoparticles, a mixture of silver nanowires and nanoparticles. The
      resistance changes show two linear response ranges to nitrite in the
      concentration ranges of 1.0 * 10-8 M to 5.0 * 10-6 M and 1.0 * 10-5 M to 3.2 * 10
      3 M, with a limit of detection of 8.5 * 10-11 M (S/N = 3). The sensor displays a
      wider linear range, a lower detection limit, a higher stability, high
      selectivity, low-volume sampling, and disposability for nitrite with respect to
      other nanoparticle- and paper-based sensors. The characterization of silver ink
      was verified by SEM, EDS, and IR studies, and the sensing mechanism is discussed.
      In addition, this paper-based sensor has been successfully employed to determine
      the nitrite content in tap, river and lake water samples.

PMID- 30295312
TI  - Interleukin-10 gene polymorphisms and chronic periodontitis susceptibility:
      Evidence based on 33 studies.
AB  - The purpose of the meta-analysis was to investigate the potential association of
      interleukin-10 (IL-10) polymorphisms with susceptibility to chronic periodontitis
      (CP). A total of 33 studies involving 3487 cases and 4356 controls were
      identified through a search of multiple electronic databases (last search was
      updated on 19 July 2018). Three single nucleotide polymorphisms (SNPs) were
      included in the meta-analysis: -1082A>G(rs1800896), -819C>T(rs1800871), and 
      592C>A(rs1800872). Odds ratios (ORs) and their 95% confidence intervals (CIs)
      using allele, dominant, and recessive genetic models were computed to assess the
      strength of the association. The -1082A>G(rs1800896) polymorphism was found to be
      associated with decreased CP risk in both Caucasians and Latinos under the
      dominant model. The -819C>T(rs1800871) and -592C>A(rs1800872) polymorphisms were
      both associated with increased CP risk in Latinos under the allele and dominant
      models. In Asians, no associations were observed for any of the polymorphisms
      under all comparison models. The present meta-analysis suggests that the 
      1082A>G(rs1800896) polymorphism might be a protective factor for CP in both
      Caucasians and Latinos, but the -819C>T(rs1800871) and -592C>A(rs1800872)
      polymorphisms might contribute to CP pathogenesis in Latinos.

PMID- 30295313
TI  - Developmental trajectories of adaptive behavior in autism spectrum disorder: a
      high-risk sibling cohort.
AB  - BACKGROUND: Children with autism spectrum disorder (ASD) often experience
      impairments in adaptive behavior. METHODS: Developmental trajectories of adaptive
      behavior in ASD were examined in children from high-risk (siblings of children
      diagnosed with ASD, n = 403) and low-risk (no family history of ASD, n = 163)
      families. Children were assessed prospectively at 12, 18, 24, and 36 months of
      age using the Vineland Adaptive Behavior Scales and underwent a blind independent
      diagnostic assessment for ASD at 36 months of age. RESULTS: The semi-parametric
      group-based modeling approach using standard scores on the Adaptive Behavior
      Composite revealed three distinct developmental trajectories: (a) Group 1 (21.2%
      of sample) showed average performance at 12 months and a declining trajectory;
      (b) Group 2 (52.8% of the sample) showed average performance at 12 months with a
      slightly declining trajectory; and (c) Group 3 (26.0% of the sample) showed a
      higher level of adaptive behavior at 12 months and a stable trajectory. The
      Mullen Scales of Early Learning Early Learning Composite and the Autism
      Observation Scale for Infants total score at 6 and 12 months predicted trajectory
      membership. CONCLUSIONS: The results emphasize heterogeneous development
      associated with ASD and the need for interventions tailored to individual
      presentations.

PMID- 30295314
TI  - Long noncoding RNA Gm6135 functions as a competitive endogenous RNA to regulate
      toll-like receptor 4 expression by sponging miR-203-3p in diabetic nephropathy.
AB  - We aim to explore the relationship between Gm6135 and diabetic nephropathy. We
      detected the relative expression levels of Gm6135 and toll-like receptor 4 (TLR4)
      in diabetic nephropathy mice and high-glucose-cultured mouse mesangial cells SV40
      MES-13 by the quantitative reverse transcription-polymerase chain reaction (qRT
      PCR) and western blot detection. Cell proliferation and apoptosis were detected
      after small interfering RNA (siRNA) interference or plasmid overexpression of
      Gm6135/TLR4, and bioinformatics method was used to predict and screen miR-203 as
      an intermediate factor. Through dual-luciferase reporter gene, RNA pull-down, qRT
      PCR, and western blot, the binding relationship between Gm6135, miR-203-3p, and
      TLR4 was confirmed. The possibility of the competing endogenous RNA mechanism was
      demonstrated by cell localization assays and rip assays. Finally, the
      proliferation of mouse mesangial cells SV40-MES-13 was detected after mimics and
      inhibitor of microRNA, which were reversed with TLR4 overexpression and siRNA.
      The results showed that the relative expression levels of Gm6135 and TLR4 in the
      kidney and high-glucose-cultured mouse mesangial cells of diabetic nephropathy
      mice increased significantly. Overexpression or downregulation of Gm6135/TLR4
      significantly affected the proliferation and apoptosis of mouse mesangial cells.
      Gm6135 upregulates TLR4 by competitively binding to miR-203-3p.

PMID- 30295315
TI  - Quantitative colocalization analysis of DNA delivery by PEI-mediated cationic
      polymers in mammalian cells.
AB  - : Although cationic polymers are widely used for DNA delivery, the relationship
      between the properties of the formed complexes and their biological activity is
      not fully understood. Here, we propose a novel procedure consisting of
      superresolved images coupled with quantitative colocalization to analyse DNA
      release in living cells. This work compares the different workflows available in
      a quantitative colocalization study of DNA delivery using polyethylenimine as
      transfection reagent. A nimble workflow with deconvolution in three-dimensional
      images was developed. Among the different colocalization coefficients, Manders'
      colocalization coefficient was the best to track the complexes. Results showed
      that DNA/polyethylenimine complexes were tightly interacting at the time of
      transfection and their disassembly was observed between 2 and 10 h after their
      uptake. Heterogenicity was found in the intracellular fate of each complex. At 24
      h, some complexes were still present underneath the nuclear envelope. Overall,
      this study opens the door for particle tracking assessment with three-dimensional
      imaging at intracellular level. LAY DESCRIPTION: DNA delivery technologies in
      living cells are of high relevance in the biotechnology field. The transient
      expression of a gene of interest enables the production of a wide range of new
      therapeutic candidates for clinical purposes. However, the introduction of an
      exogenous DNA construct into a cell culture requires the use of certain vehicles
      that protect the DNA from host cell DNases and deliver it into the cell nucleus.
      From the different systems available, polyethylenimine (PEI) has been extensively
      used in transient gene expression strategies for the last three decades. However,
      the intracellular fate of the formed DNA/PEI complexes and the DNA release from
      the complexes is still poorly understood. In this work, we propose the
      application of combined superresolved images through mathematical deconvolution
      to colocalization studies of DNA/PEI complexes evolution in living mammalian cell
      cultures. Both specimens were covalently labelled with Cy3 and Cy5 dye,
      respectively, and the kinetics of its disassembly process within the cells was
      tracked over the time. Because of the specific features of the formed-complexes,
      a comparative study of the different colocalization coefficients was performed
      towards optimizing the analysis of these particles with confocal microscopy.
      Besides, the 3D imaging of the process allowed the direct visualization of a
      partial DNA/PEI complexes disassembly and the location of those complexes
      underneath the nuclear envelope during the cell production phase (24 h after the
      uptake).

PMID- 30295316
TI  - Vitamin D attenuates human gingival fibroblast inflammatory cytokine production
      following advanced glycation end product interaction with receptors for AGE.
AB  - BACKGROUND AND OBJECTIVES: Vitamin D [1,25(OH)2 D3 or 1,25D3] is critical in
      musculoskeletal health, inflammation, immune response, and glucose metabolism.
      Patients with vitamin D deficiency may be at higher risk of diabetes and
      periodontitis. Diabetic patients exhibit exacerbated inflammation and more
      periodontal destruction. Advanced glycation end products (AGEs), formed during
      diabetic hyperglycemia, activate inflammatory pathways in periodontitis. Human
      gingival fibroblasts (HGFs) express receptors for AGEs (RAGEs) and can contribute
      to inflammation. OBJECTIVES: Determine whether glycated human serum albumin (G
      HSA) augments HGF IL-6 and IL-8 production, and whether treatment with 1,25D3
      attenuates cytokine production following stimulation with G-HSA + IL-1beta and/or
      IL-17. MATERIAL AND METHODS: HGFs were incubated +/-G-HSA or normal human serum
      albumin (HSA), +/-IL-1beta and/or IL-17, +/-1,25D3. Cytokines were measured by
      ELISA. Neutralizing anti-RAGE was used to assess AGE-RAGE interaction. Endotoxin
      was measured using the ToxinSensorTM System. Data were expressed as mean +/-
      standard deviation and analyzed using a one-way analysis of variance (ANOVA) and
      Scheffe's F procedure for post hoc comparisons. RESULTS: G-HSA or IL-1beta, but
      not HSA, significantly stimulated IL-6 and IL-8 production. G-HSA or HSA when
      combined with IL-1beta or IL-1beta + IL-17 synergistically stimulated IL-6 and IL
      8. Neutralizing anti-RAGE inhibited IL-6 and IL-8 produced by cells stimulated
      with IL-1beta + G-HSA but not (+HSA). Synergism caused by HSA did not appear to
      be mediated by endotoxin since its levels in G-HSA and HSA were not sufficient to
      stimulate fibroblasts. Vitamin D inhibited IL-6 and IL-8 production stimulated by
      G-HSA or HSA + IL-1beta or IL-1beta + IL-17. CONCLUSIONS: Results suggest that
      the "perioprotective" effects of vitamin D are related to its ability to regulate
      inflammatory cytokine production by HGFs following AGE-RAGE interaction.

PMID- 30295317
TI  - From Early Relationships to Preacademic Knowledge: A Sociocognitive Developmental
      Cascade to School Readiness.
AB  - This study aimed to test a four-wave sequential mediation model linking mother
      child attachment to children's school readiness through child executive
      functioning (EF) and prosociality in toddlerhood and the preschool years. Mother
      child attachment security was assessed when children (N = 255) were aged 15
      months and 2 years, child EF at age 2, prosocial behavior at age 4, and finally
      cognitive school readiness in kindergarten (age 6). The results revealed three
      indirect pathways linking attachment to school readiness: one through EF only,
      one through prosocial behavior only, and a last pathway involving both EF and
      prosocial behavior serially. These findings suggest that secure attachment may
      equip children with both cognitive and social skills that are instrumental to
      their preparedness for school.

PMID- 30295318
TI  - New perspectives on binding in visual working memory.
AB  - How does visual working memory (WM) store the binding between different features
      of a visual object (like colour, orientation, and location), and does memorizing
      these bindings require additional resources beyond memorizing individual
      features? These questions have traditionally been addressed by comparing
      performance across different types of change detection task. More recently,
      experimental tasks such as analogue (cued) recall, combined with analysis methods
      including Bayesian hypothesis testing and formal model comparison, have shed new
      light on the properties of WM. A significant new perspective is that noise in
      neural representation limits the precision of recall, and several recent models
      incorporate this view to account for failures of binding in WM. We review the
      literature on feature binding with a focus on these new developments and discuss
      their implications for the interpretation of classical findings.

PMID- 30295319
TI  - A Family Focused Intervention Influences Hippocampal-Prefrontal Connectivity
      Through Gains in Self-Regulation.
AB  - The stressors associated with poverty increase the risks for externalizing
      psychopathology; however, specific patterns of neurobiology and higher self
      regulation may buffer against these effects. This study leveraged a randomized
      control trial, aimed at increasing self-regulation at ~11 years of age. As
      adults, these same individuals completed functional MRI scanning (Mage  = 24.88
      years; intervention n = 44; control n = 49). Functional connectivity between the
      hippocampus and ventromedial prefrontal cortex was examined in relation to the
      intervention, gains in self-regulation, and present-day externalizing symptoms.
      Increased connectivity between these brain areas was noted in the intervention
      group compared to controls. Furthermore, individual gains in self-regulation,
      instilled by the intervention, statistically explained this brain difference.
      These results begin to connect neurobiological and psychosocial markers of risk
      and resiliency.

PMID- 30295320
TI  - Rehabilitation Services Use of Older Adults According to Fall-Risk Screening
      Guidelines.
AB  - OBJECTIVES: To characterize rehabilitation services use of older adults according
      to fall-risk classification based on screening guidelines. DESIGN: Cross
      sectional analysis of 2015 National Health and Aging Trends Study. SETTING: Study
      participants' homes. PARTICIPANTS: National sample of 7,440 community-dwelling
      Medicare beneficiaries. MEASUREMENTS: In-person interviews and functional
      assessments. Based on Centers for Disease Control and Prevention Stopping Elderly
      Accidents, Deaths and Injuries criteria, participants were classified as low,
      moderate, or high fall risk. RESULTS: Twenty-three percent of older adults
      classified as moderate fall-risk (n = 2602) and 40.6% of those at high fall-risk
      (n = 940) reported rehabilitation services use in the past year. Among older
      adults who reported rehabilitation services in the past year (n = 1,505),
      treatment to address falls was reported by 2.8%, 12.6%, and 34.7% of those
      classified with low, moderate, and high fall-risk, respectively (p < 0.001).
      Older adults with high fall-risk who did not receive rehabilitation services had
      significantly better self-reported physical capacity (p = 0.02) but comparable
      physical performance (all p's > 0.05) relative to those who received
      rehabilitation. CONCLUSION: Older adults at high risk for falls were
      significantly more likely to report rehabilitation services use compared to those
      with low and moderate risk of falling. The findings also indicate that there is
      low adherence to national clinical recommendations for rehabilitation services
      use in older adults vulnerable to falls-related injury. Among the high fall-risk
      group, those who did not receive rehabilitation services had similarly low
      physical function as compared with those who received rehabilitation, indicating
      potential unmet need to address physical impairments related to fall-risk.

PMID- 30295322
TI  - Electroconvulsive therapy in unipolar depression treatment guidelines.

PMID- 30295321
TI  - Differential Effects of Salient Visual Events on Memory-Guided Attention in
      Adults and Children.
AB  - Both salient visual events and scene-based memories can influence attention, but
      it is unclear how they interact in children and adults. In Experiment 1, children
      (N = 27; ages 7-12) were faster to discriminate targets when they appeared at the
      same versus different location as they had previously learned or as a salient
      visual event. In contrast, adults (N = 30; ages 18-31) responded faster only when
      cued by visual events. While Experiment 2 confirmed that adults (N = 27) can use
      memories to orient attention, Experiment 3 showed that, even in the absence of
      visual events, the effects of memories on attention were larger in children (N =
      27) versus adults (N = 28). These findings suggest that memories may be a robust
      source of influence on children's attention.

PMID- 30295323
TI  - Maternal Depressive Symptoms During the Pre- and Postnatal Periods and Infant
      Attention to Emotional Faces.
AB  - We examined how infants' attentional disengagement from happy, fearful, neutral,
      and phase-scrambled faces at 8 months, as assessed by eye tracking, is associated
      with trajectories of maternal depressive symptoms from early pregnancy to 6
      months postpartum (decreasing n = 48, increasing n = 34, and consistently low
      symptom levels n = 280). The sample (mother-infant dyads belonging to a larger
      FinnBrain Birth Cohort Study) was collected between 5/2013-6/2016. The overall
      disengagement probability from faces to distractors was not related to maternal
      depressive symptoms, but fear bias was heightened in infants whose mothers
      reported decreasing or increasing depressive symptoms. Exacerbated attention to
      fearful faces in infants of mothers with depressive symptoms may be independent
      of the timing of the symptoms in the pre- and postnatal stages.

PMID- 30295324
TI  - The periodontal stem/progenitor cell inflammatory-regenerative cross talk: A new
      perspective.
AB  - Adult multipotent stem/progenitor cells, with remarkable regenerative potential,
      have been isolated from various components of the human periodontium. These
      multipotent stem/progenitor cells include the periodontal ligament
      stem/progenitor cells (PDLSCs), stem cells from the apical papilla (SCAP), the
      gingival mesenchymal stem/progenitor cells (G-MSCs), and the alveolar bone proper
      stem/progenitor cells (AB-MSCs). Whereas inflammation is regarded as the reason
      for tissue damage, it also remains a fundamental step of any early healing
      process. In performing their periodontal tissue regenerative/reparative activity,
      periodontal stem/progenitor cells interact with their surrounding inflammatory
      micro-environmental, through their expressed receptors, which could influence
      their fate and the outcome of any periodontal stem/progenitor cell-mediated
      reparative/regenerative activity. The present review discusses the current
      understanding about the interaction of periodontal stem/progenitor cells with
      their surrounding inflammatory micro-environment, elaborates on the inflammatory
      factors influencing their stemness, proliferation, migration/homing,
      differentiation, and immunomodulatory attributes, the possible underlying
      intracellular mechanisms, as well as their proposed relationship to the canonical
      and noncanonical Wnt pathways.

PMID- 30295325
TI  - A novel IkB kinase inhibitor attenuates ligature-induced periodontal disease in
      mice.
AB  - BACKGROUNDS AND OBJECTIVES: IMD-0354 is a novel I kappa-B kinase (IKK) inhibitor,
      which regulates inflammation. The purpose of this study was to examine the effect
      of the reagent on bone loss for ligature-induced periodontitis. MATERIAL AND
      METHODS: We ligated around the upper right second molars of 8-week-old C57BL/6J
      mice in the split-mouth model. The test mice were injected intraperitoneally with
      IMD-0354 before the placement of the ligature. The control mice were injected
      intraperitoneally with 0.5% carboxymethylcellulose (CMC) as vehicle before the
      placement of the ligature. To determine the optimum concentration of the reagent
      on ligature-induced periodontitis in the mice, we examined the effect of three
      types of concentration, which were 1, 5, and 10 mg/kg of IMD-0354, as a
      preliminary experiment. After we determined 10 mg/kg as the optimum concentration
      for the IMD group by micro-CT analysis, both the IMD and CMC groups (n = 15 each
      in total, including all the analyses) were subdivided into two small groups,
      respectively, for further analyses: I group (unligated side of IMD group), IL
      group (ligated side of IMD group), C group (unligated side of CMC group) and CL
      group (ligated side of CMC group). The mice in the IMD and CMC groups were
      treated with each reagent daily and sacrificed 8 days after the ligation. For
      assessment of bone resorption, we performed micro-CT and histological analyses.
      We also carried out real-time PCR to investigate proinflammatory and bone
      metabolic markers. RESULTS: There were significant differences for linear bone
      loss and volumetric parameter in the test (IMD) group compared to the control
      (CMC) group 8 days after ligation. In terms of the mRNA expression level of
      gingival tissue, the level of RANKL was significantly suppressed in the IMD group
      compared to the CMC group. IMD-0354 also tended to suppress the levels of
      interleukin-1 beta, tumor necrosis factor-alpha, and osteoprotegerin. For
      histological analysis, the relative numbers of TRAP-positive multinucleated cells
      decreased significantly in the IMD group compared to the CMC group. CONCLUSION:
      IMD-0354 regulated bone resorption by ligature-induced periodontitis, and it is
      suggested that the inhibition of IKK via down-regulation of NF kappa-B may
      provide periodontal patients with an effective approach to prevent or suppress
      the disease.

PMID- 30295326
TI  - A qualitative study of home visiting as a palliative care strategy to follow-up
      cancer patients by nurses in clinical setting in a developing country.
AB  - AIMS: The aims are to examine the effect of home visiting and resources for
      instituting the programme as a follow-up strategy in integration of palliative
      care in daily clinical practice by nurses caring for cancer patients in Nigeria,
      and on how it can be used to improve care for cancer patients. BACKGROUND: Home
      visiting by nurses has been used as a follow-up option in maternal and child
      health care globally. Most cancer patients default after diagnosis, home visiting
      offers potential as a strategy for follow-up of these patients too. METHODS: This
      was a qualitative study which employed a focus group discussion with nurse
      managers and interviews with cancer in-patients in two teaching hospitals in
      Nigeria. It utilised an interpretive paradigm to reach the best understanding of
      the problem. A total of 19 nurse managers who were directly involved with the
      care of cancer patients and 11 cancer patients participated in the study between
      July and September 2016. A qualitative content analysis was employed to analyse
      the data. FINDINGS: Nine major themes were identified in relation to perceived
      benefits of home visiting services and six in relation to needed resources in
      instituting the programme. Similar findings emerged from both the focus group
      discussions and the interviews with patients. Participants agreed that visiting
      cancer patients would ease many problems commonly encountered by patients
      following diagnosis of cancer, including psychological, financial, and emotional
      problems. Needed resources included hospital policies, adequate staff strength,
      staff commitment and funding. CONCLUSIONS: Viable home visiting requires
      palliative care teams to carry out the service and hospital policy to direct
      their activities. Putting this into practice will be in line with World Health
      Organisation (WHO) advocacy of integrated palliative care for chronic diseases.

PMID- 30295327
TI  - Sharing Positive Experiences Boosts Resilient Thinking: Everyday Benefits of
      Social Connection and Positive Emotion in a Community Sample.
AB  - The influence of shared enjoyment and positive affect (PA) on resilient thinking
      was examined in 191 middle-aged adults (40-65 years), participating in a study of
      resilience. Participants completed diaries assessing positive events, shared
      enjoyment, PA, and resilient cognitions (RC). Multilevel structural equation
      modeling was utilized to examine when and who engages in RC. Participants
      reported more RC on days they experienced more positive experiences. This
      relationship was explained by shared enjoyment and PA. Level-1 proportional
      reduction of variance (PRV) for shared enjoyment, PA, and RC was 9%, 10%, and
      35%, respectively. Individuals reporting more positive experiences trended toward
      a more resilient mindset; PA accounted for this relationship. Shared enjoyment
      mediated the relationship between interpersonal events and PA. These findings
      suggest PA is integral to having a resilient mindset, and shared enjoyment is a
      potential mechanism that may influence PA. Level-2 PRV for shared enjoyment, PA,
      and RC was 22%, 21%, and 55%, respectively. RC were associated with less
      depression and anxiety; and greater well-being, vitality, and physical
      functioning at follow-up.

PMID- 30295328
TI  - Efficacy of sonically, ultrasonically and laser-activated irrigation in removing
      a biofilm-mimicking hydrogel from an isthmus model.
AB  - AIM: To evaluate the efficacy of sonically, ultrasonically and laser-activated
      irrigation (LAI) in removing a biofilm-mimicking hydrogel from the isthmus in a
      root canal model. METHODOLOGY: Transparent resin blocks containing two
      standardized root canals (apical diameter of 0.3 mm, 6% taper, 16 mm long, with a
      coronal reservoir) connected by an isthmus (0.15 mm wide, 2 mm high) were used as
      the test model. The isthmus was filled with a hydrogel-containing dentine debris.
      The canals were filled with irrigant, and the models were randomly assigned to
      the following activation groups (n = 20): EndoActivator (EA), Eddy,
      ultrasonically activated irrigation (UAI) with an Irrisafe 25 mm length, size 25
      file and LAI with a 2940 nm Er:YAG-laser (20 Hz, 50 MUs, 20 mJ, PIPS tip at the
      canal entrance). All protocols were executed for 3 * 20 s. Needle irrigation (NI)
      with a 27G needle served as the control. Standardized images of the isthmus were
      taken before and after irrigation, and the amount of removed hydrogel was
      determined using image analysis software and compared across groups using Welch
      anova (P <= 0.05). RESULTS: Hydrogel removal was greatest in the LAI group
      (90.2%) and was significantly greater than that with UAI, EA and NI (P <= 0.014),
      but not significantly different from Eddy (P = 0.498). Hydrogel removal with Eddy
      (85.9%) was significantly greater than that with NI and EA (P < 0.05), but not
      significantly different from UAI (P = 0.07). There was no significant difference
      between the NI and EA groups (P = 1). CONCLUSIONS: Laser-activated irrigation and
      Eddy resulted in the greatest hydrogel removal and performed better than EA and
      UAI. The effect of LAI was also not dependent on deep intracanal tip placement.

PMID- 30295329
TI  - Comparing the effects of drawing and verbal recall techniques on children's
      memory accounts.
AB  - The present study compared the amount and accuracy of information Taiwanese
      children reported about a staged event in verbal-only and drawing-assisted
      interviews. We also tested further whether verbosity was a valid indicator of the
      accuracy of children's memory reports (Koriat & Goldsmith, , ) in a non-Western
      sample. Eighty-four first-grade elementary school children participated in a
      staged event involving a novel interactive puppet show followed by a drawing
      activity (drawing of the target event or the school), and were subsequently given
      a 10-minute memory interview. They were randomly assigned to a verbal cued-recall
      interview condition or a drawing-assisted interview condition. We did not find
      significant differences in the amount and accuracy of details reported between
      the two interview conditions. Our findings also revealed that the quantity of
      children's reports was positively related to the number of correct details
      reported, indicating that the children in our study did not demonstrate a
      quantity-accuracy tradeoff.

PMID- 30295330
TI  - Ascariasis as a model to study the helminth/allergy relationships.
AB  - Ascariasis is the most frequent soil transmitted helminthiasis and, as well as
      other helminth infections, is expected to influence the clinical presentation of
      allergic diseases such as asthma. Indeed, several clinical and experimental works
      have shown an important impact either increasing or suppressing symptoms, and the
      same effects have been detected on the underlying immune responses. In this
      review we analyze the work on this field performed in Colombia, a Latin American
      tropical country, including aspects such as the molecular genetics of the IgE
      response to Ascaris; the allergenic activity of Ascaris IgE-binding molecular
      components and the immunological and clinical influences of ascariasis on asthma.
      The analysis allows us to conclude that the impact of ascariasis on the inception
      and evolution of allergic diseases such as asthma deserves more investigation,
      but advances have been made during the last years. The concurrent parasite
      induced immunostimulatory and immunosuppressive effects during this helminthiasis
      do modify the natural history of asthma and some aspects of the practice of
      allergology in the tropics. Theoretically it can also influence the
      epidemiological trends of allergic diseases either by its absence or presence in
      different regions and countries.

PMID- 30295331
TI  - Providing oral care for adults with mental health disorders: Dental
      professionals' perceptions and experiences in Perth, Western Australia.
AB  - OBJECTIVE: To explore dental professionals' perceptions and experiences of
      providing oral health care for adults with mild to moderate mental health
      disorders (MHD) in Perth, Western Australia. METHODS: A grounded theory approach
      guided this research which comprised semi-structured interviews with oral health
      professionals working in private and/or public dental facilities attended by
      adults with MHD. An iterative analysis of transcripts identified emerging issues
      that were organized into categories under which key themes were noted, coded,
      compared, discussed, reviewed and revised independently by two researchers to
      ensure rigour. RESULTS: Sixteen interviews were conducted with six general
      dentists, three dental specialists, four oral health therapists (OHT) and three
      dental assistants. Barriers to providing oral health care for adults with MHD
      included limitations of the current model of care, often focused on treating
      advanced disease; limited inter-professional collaboration; an over-burdened
      public dental system and the financial constraints of private practice. Personal
      barriers included perceptions that people with MHD had limited capacity for self
      care and preventing oral disease. Factors that would enable oral health care
      included training and professional development for dental professionals to work
      effectively with people with MHD and a more flexible, inter-professional approach
      that involved prevention and inviting family to consultations about oral health
      in primary health care settings. CONCLUSIONS: Our study reveals structural
      barriers where services often appear to be inadequately prepared to meet the oral
      health needs of people with MHD. This suggests the need for strategies to review
      current models of care and encourage and support dental professionals to provide
      oral health care that is inclusive, inter-professional, focused on prevention and
      sensitive to the social context and lived experience of people with MHD.

PMID- 30295332
TI  - Erratum.

PMID- 30295333
TI  - Virtual reality and cardiac anatomy: Exploring immersive three-dimensional
      cardiac imaging, a pilot study in undergraduate medical anatomy education.
AB  - Cardiac anatomy can be challenging to grasp because of its complex three
      dimensional nature and remains one of the most challenging topics to teach. In
      light of some exciting technological advances in the field of virtual reality
      (VR), we sought to test the viability and the assess efficacy of this computer
      generated model for the purposes of teaching cardiac anatomy. Before learning
      cardiac anatomy, first-year undergraduate medical students participated in an
      anatomically correct VR simulation of the heart. Students were randomly
      distributed into control and variable groups. Each student completed a pre
      intervention quiz, consisting of 10 multiple choice questions with 5 conventional
      cardiac anatomy questions and 5 visual-spatial (VS) questions. The control group
      continued to independent study, whereas the variable group subjects were exposed
      to a 30-min immersive cardiac VR experience. At the end of the intervention, both
      the groups underwent a separate post-intervention 10-question quiz. Forty-two
      students participated in the cardiac VR experiment, separated into 14 control and
      28 variable subjects. They scored 50.9% on average on the pre-intervention quiz
      (SD = 16.5) and 70.2% on the post-intervention quiz (SD = 18.7). Compared to the
      control group, the students exposed to VR scored 21.4% higher in conventional
      content (P = 0.004), 26.4% higher in VS content (P < 0.001), and 23.9% higher
      overall (P < 0.001). VR offers an anatomically correct and immersive VS
      environment that permits learner to interact three-dimensionally with the heart's
      anatomy. This study demonstrates the viability and the effectiveness of VR in
      teaching cardiac anatomy. Clin. Anat., 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30295334
TI  - Characteristics of myeloproliferative neoplasms in patients exposed to ionizing
      radiation following the Chernobyl nuclear accident.
AB  - Myeloproliferative neoplasms (MPNs) driver mutations are usually found in JAK2,
      MPL, and CALR genes; however, 10%-15% of cases are triple negative (TN). A
      previous study showed lower rate of JAK2 V617F in primary myelofibrosis patients
      exposed to low doses of ionizing radiation (IR) from Chernobyl accident. To
      examine distinct driver mutations, we enrolled 281 Ukrainian IR-exposed and
      unexposed MPN patients. Genomic DNA was obtained from peripheral blood
      leukocytes. JAK2 V617F, MPL W515, types 1- and 2-like CALR mutations were
      identified by Sanger Sequencing and real time polymerase chain reaction.
      Chromosomal alterations were assessed by oligo-SNP microarray platform.
      Additional genetic variants were identified by whole exome and targeted
      sequencing. Statistical significance was evaluated by Fisher's exact test and
      Wilcoxon's rank sum test (R, version 3.4.2). IR-exposed MPN patients exhibited a
      different genetic profile vs unexposed: lower rate of JAK2 V617F (58.4% vs 75.4%,
      P = .0077), higher rate of type 1-like CALR mutation (12.2% vs 3.1%, P = .0056),
      higher rate of TN cases (27.8% vs 16.2%, P = .0366), higher rate of potentially
      pathogenic sequence variants (mean numbers: 4.8 vs 3.1, P = .0242). Furthermore,
      we identified several potential drivers specific to IR-exposed TN MPN patients:
      ATM p.S1691R with copy-neutral loss of heterozygosity at 11q; EZH2 p.D659G at 7q
      and SUZ12 p.V71 M at 17q with copy number loss. Thus, IR-exposed MPN patients
      represent a group with distinct genomic characteristics worthy of further study.

PMID- 30295335
TI  - Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell
      disease: A SUSTAIN study analysis.
AB  - The cell adhesion molecule P-selectin plays a key role in the pathogenesis of a
      vaso-occlusive crisis (VOC) in patients with sickle cell disease (SCD). In the
      double-blind, placebo-controlled phase 2 SUSTAIN study, crizanlizumab (humanized,
      anti-P-selectin monoclonal antibody) 5 mg/kg significantly lowered the rate of
      VOC in patients with SCD by 45% vs placebo. In SUSTAIN, patients with SCD were
      randomized to crizanlizumab 2.5 mg/kg, crizanlizumab 5 mg/kg, or placebo
      intravenously 14 times over 52 weeks. The primary endpoint was the annual rate of
      VOC with crizanlizumab vs placebo. This post hoc descriptive analysis evaluated
      the proportion of patients who did not experience a VOC during the study in the
      following subgroups: VOCs in the year prior to study entry (2-4/5-10), SCD
      genotype (HbSS/non-HbSS), and concomitant hydroxyurea use (yes/no). More patients
      were VOC event-free in the crizanlizumab 5 mg/kg arm than in the placebo arm,
      including those with more frequent prior VOCs (ie, 5-10; 28.0% vs 4.2%), the HbSS
      genotype (31.9% vs 17.0%) and/or using concomitant hydroxyurea (33.3% vs 17.5%).
      Further analyses of secondary endpoints demonstrated that crizanlizumab treatment
      significantly increased time-to-first VOC vs placebo in these subgroups. The
      rates of treatment-emergent adverse events were similar between treatment arms
      across all subgroups. This post hoc analysis of SUSTAIN shows that in patients
      with a high number of prior VOCs, on concomitant hydroxyurea and/or with the HbSS
      genotype, crizanlizumab treatment increases the likelihood of patients being VOC
      event-free and delays time-to-first VOC.

PMID- 30295337
TI  - An unusual hemoglobinopathy: compound heterozygosity for hemoglobins C and E.

PMID- 30295336
TI  - High NEK2 confers to poor prognosis and contributes to cisplatin-based
      chemotherapy resistance in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a common malignant tumor in southern China and
      Southeast Asia, but the molecular mechanism of its pathogenesis is poorly
      understood. Our previous work demonstrated that NEK2 is overexpressed in multiple
      cancers. However, how NEK2 involves in NPC development remains to be elucidated.
      In this study, we firstly identified NEK2, located at +1q32-q33, a late event in
      NPC pathogenesis, overexpressed in the stage III-IV and paired sequential
      recurrent patients with NPC by immunohistochemistry. Furthermore, Kaplan-Meier
      analysis indicated high NEK2 conferred an inferior overall survival in NPC. In
      addition, cisplatin experiments with cell counting kit-8, colony formation, and a
      xenograft mice model of NPC demonstrated that NEK2 contributed to proliferation
      and cisplatin resistance in vitro and in vivo. On the contrary, downregulation of
      NEK2 by short hairpin RNA inhibited NPC cell growth and increased the sensitivity
      of cisplatin treatment in vitro. Thus, increased expression of NEK2 protein could
      not be predicted for poor survival but used as a novel biomarker for recurrence
      of NPC. Targeting NEK2 has the potential to eradicate the cisplatin-based
      chemotherapy resistant NPC cells.

PMID- 30295338
TI  - Fingolimod enhances the efficacy of delayed alteplase administration in acute
      ischemic stroke by promoting anterograde reperfusion and retrograde collateral
      flow.
AB  - OBJECTIVE: The present study was undertaken to determine the efficacy of
      coadministration of fingolimod with alteplase in acute ischemic stroke patients
      in a delayed time window. METHODS: This was a prospective, randomized, open
      label, blinded endpoint clinical trial, enrolling patients with internal carotid
      artery or middle cerebral artery proximal occlusion within 4.5 to 6 hours from
      symptom onset. Patients were randomly assigned to receive alteplase alone or
      alteplase with fingolimod. All patients underwent pretreatment and 24-hour
      noncontrast computed tomography (CT)/perfusion CT/CT angiography. The coprimary
      endpoints were the decrease of National Institutes of Health Stroke Scale scores
      over 24 hours and the favorable shift of modified Rankin Scale score (mRS)
      distribution at day 90. Exploratory outcomes included vessel recanalization,
      anterograde reperfusion, and retrograde reperfusion of collateral flow. RESULTS:
      Each treatment group included 23 patients. Compared with alteplase alone,
      patients receiving fingolimod plus alteplase exhibited better early clinical
      improvement at 24 hours and a favorable shift of mRS distribution at day 90. In
      addition, patients who received fingolimod and alteplase exhibited a greater
      reduction in the perfusion lesion accompanied by suppressed infarct growth by 24
      hours. Fingolimod in conjunction with alteplase significantly improved
      anterograde reperfusion of downstream territory and prevented the failure of
      retrograde reperfusion from collateral circulation. INTERPRETATION: Fingolimod
      may enhance the efficacy of alteplase administration in the 4.5- to 6-hour time
      window in patients with a proximal cerebral arterial occlusion and salvageable
      penumbral tissue by promoting both anterograde reperfusion and retrograde
      collateral flow. These findings are instructive for the design of future trials
      of recanalization therapies in extended time windows. Ann Neurol 2018;84:725-736.

PMID- 30295340
TI  - Effect of low androgen levels on the sulphur dioxide signalling pathway in rat
      penile corpus cavernosum.
AB  - The aim of this study was to investigate the relationship between sulphur dioxide
      (SO2 ) signalling pathway and the changes in erectile function under low androgen
      levels. Thirty-six healthy male Sprague Dawley (SD) rats aged eight weeks were
      randomly divided into androgen replacement group, castration group and sham
      group. Rats in the androgen replacement group were subcutaneously injected with
      testosterone propionate at 3 mg/kg every other day postcastration. The maximum
      intracavernous pressure/mean arterial pressure (ICPmax /MAP) and the relative
      content of SO2 in the penile corpus cavernosum were measured. The mRNA and
      protein expressions of aspartate aminotransferase (AAT1 and AAT2), cysteine
      oxidase (CDO), endothelial nitric oxide synthase (eNOS) and phosphorylation of
      endothelial nitric oxide synthase (P-eNOS) were detected. ICPmax /MAP, P
      eNOS/eNOS and the level of SO2 decreased significantly in the castration group
      compared to the other groups (p < 0.05). The expressions of mRNA and protein
      decreased significantly in the castration group compared to the androgen
      replacement group and the sham group (p < 0.05), while there was no significant
      difference between the androgen replacement group and sham group. Low androgen
      levels can inhibit erectile function by downregulating the SO2 signalling
      pathway.

PMID- 30295341
TI  - The impact of China's latest population policy changes on maternity insurance-a
      case study in Jiangsu Province.
AB  - This study aims to examine the impact of China's population policy changes on
      social insurance. Nearly 4 decades ago, China ushered in the 1-child policy as a
      family planning policy to control the adverse effect of high population growth.
      The current maternity insurance system in China is designed to fit the operations
      of the 1-child policy. However, the implementation of the comprehensive 2-child
      policy can pose a challenge to the sustainability of the current maternity
      insurance scheme hence the call for reform. The study empanels a novel and
      comprehensive system dynamic model that incorporates all the related factors that
      influence the income and expenditure of maternity insurance in the Jiangsu
      Province. Data are mainly derived from the historical data of the Statistical
      Yearbook of Jiangsu Province and the National Bureau of Statistics of China.
      These are used to construct and simulate a system dynamic model to determine a
      sustainable contribution rate for maternity insurance. In conclusion, if the rate
      of contribution of the current maternity insurance policy is not increased, the
      burden of implementing the comprehensive 2-child policy will exacerbate the
      current deficit balance of the maternity insurance fund. The existing maternity
      insurance benefits thus cannot be maintained, and women's health will be
      threatened. In the short term, the study proposes an increase in the rate of
      premium payment to prolong the life of the maternity insurance. In the long term,
      there is a need to improve the level of coordination and expand the coverage of
      maternity insurance.

PMID- 30295342
TI  - Evaluation of chemical and morphological changes in radicular dentin after
      different final surface treatments.
AB  - The aim of this study was to evaluate the chemical and morphological effects of
      different lasers as a final surface treatment for endodontic therapy through
      energy dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM)
      respectively. Twenty-five maxillary canines were selected and instrumented with
      K3 system. Roots were randomly distributed into five groups (n = 5) according to
      the surface treatment: GI (distilled water), GII (NaOCl + EDTA), GIII (NaOCl +
      EDTA + 980 nm diode laser), GIV (NaOCl + EDTA+ 1,064 nm Nd:YAG laser), and GV
      (NaOCl + EDTA+ 2,780 nm Er, Cr:YSGG laser). Lasers were applied for 20 s and
      samples were bisected, exposing the treated surface and then subjected to
      elements quantification by EDS and morphological evaluation by scanning electron
      microscope (SEM). EDS data were submitted to ANOVA-two way, and SEM scores were
      submitted to two-way Kruskal-Wallis and Dunn's tests. The EDS analysis showed no
      difference for the chemical elements and Ca/P ratio between groups (p > .05).
      Statistical analysis showed more intense results for GV and less intense results
      for GI (p < .05). The GIII showed an amorphous organic matrix surface, while GV
      provided greater removal of intertubular dentin forming craters, and GIV promoted
      dentin fusion. The EDS method used in this study was not able to verify any
      chemical changes in root canal dentin; Nd:YAG, Er, Cr:YSGG, and 980 nm diode
      laser were capable of modifying the dentin morphology, correlating
      characteristics features for each one, which are essential clinical knowledge to
      establish the correct indication for each case. RESEARCH HIGHLIGHTS: EDS was not
      able to verify any chemical changes in root canal dentin after 980 nm diode,
      Nd:YAG and Er;Cr:YSGG laser treatments Nd:YAG, Er, Cr:YSGG, and 980 nm diode
      laser modified dentin morphology, correlating characteristics features for each
      one.

PMID- 30295343
TI  - Pitfalls in Liver MRI: Technical Approach to Avoiding Misdiagnosis and Improving
      Image Quality.
AB  - : The following is an illustrative review of common pitfalls in liver MRI that
      may challenge interpretation. This article reviews common technical and
      diagnostic challenges encountered when interpreting dynamic multiphasic T1 
      weighted imaging, hepatobiliary phase imaging, and diffusion-weighted imaging of
      the liver. Additionally, each section includes suggestions for avoiding
      diagnostic and technical errors. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 2
      J. Magn. Reson. Imaging 2018.

PMID- 30295345
TI  - Demonstration of circumferential heterogeneity in displacement and strain in the
      abdominal aortic wall by spiral cine DENSE MRI.
AB  - BACKGROUND: Knowledge of tissue properties of the abdominal aorta can improve
      understanding of vascular disease and guide interventional approaches. Existing
      MRI methods to quantify aortic wall displacement and strain are unable to discern
      circumferential heterogeneity. PURPOSE: To assess regional variation in abdominal
      aortic wall displacement and strain as a function of circumferential position
      using spiral cine displacement encoding with stimulated echoes (DENSE). STUDY
      TYPE: Prospective. POPULATION: Cardiovascular disease-free men (n = 8) and women
      (n = 9) ages 30-42. SEQUENCES: Prospective electrocardiogram (ECG)-gated and
      navigator echo-gated spiral, cine 2D DENSE and retrospective ECG-gated phase
      contrast MR (PCMR) sequences at 3T. ASSESSMENT: In-plane displacement values of
      the aortic wall acquired with DENSE were used to determine radial and
      circumferential aortic wall motion. A quadrilateral-based 2D strain calculation
      method was implemented to determine strain from the displacement field. Peak
      displacement and its radial and circumferential contributions as well as peak
      circumferential strain were compared among eight circumferential wall segments.
      Distensibility was calculated using PCMR and compared with homogenized
      circumferential strain. STATISTICAL TESTS: To account for repeated measurements
      in volunteers, linear mixed models for mean sector values were created for
      displacement magnitude, circumferential displacement, radial displacement, and
      circumferential strain. Comparisons were made between sectors. Calculated
      distensibility and homogenized circumferential strain were compared using Bland
      Altman analysis. Statistical significance was defined as P < 0.05. RESULTS:
      Displacement was highest in the anterior wall (1.5 +/- 0.7 mm) and was primarily
      in the radial as compared with circumferential direction (1.04 +/- 0.05 mm vs.
      0.81 +/- 0.42 mm). Circumferential strain was highest in the lateral walls (left
      0.16 +/- 0.05 and right 0.21 +/- 0.12) with homogenized circumferential strain of
      0.14 +/- 0.05. DATA CONCLUSION: DENSE imaging in the abdominal aortic wall
      demonstrated that the anterior aortic wall exhibits the greatest displacement,
      while the lateral wall experiences the largest circumferential strain. LEVEL OF
      EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 30295344
TI  - Rapid compositional mapping of knee cartilage with compressed sensing MRI.
AB  - More than a decade after the introduction of compressed sensing (CS) in MRI,
      researchers are still working on ways to translate it into different research and
      clinical applications. The greatest advantage of CS in MRI is the reduced amount
      of k-space data needed to reconstruct images, which can be exploited to reduce
      scan time or to improve spatial resolution and volumetric coverage. Efficient
      data acquisition using CS is extremely important for compositional mapping of the
      musculoskeletal system in general and knee cartilage mapping techniques in
      particular. High-resolution quantitative information about tissue biochemical
      composition could be obtained in just a few minutes using CS MRI. However, in
      order to make this goal a reality, some issues still need to be addressed. In
      this article we review the current state of the art of CS methods for rapid
      compositional mapping of knee cartilage. Specifically, data acquisition
      strategies, image reconstruction algorithms, and data fitting models are
      discussed. Different CS studies for T2 and T1rho mapping of knee cartilage are
      reviewed, with illustrative results. Future directions, opportunities, and
      challenges of rapid compositional mapping techniques are also discussed. Level of
      Evidence: 4 Technical Efficacy: Stage 6 J. Magn. Reson. Imaging 2018;47:1185
      1198.

PMID- 30295346
TI  - Differences between FLIM phasor analyses for data collected with the Becker and
      Hickl SPC830 card and with the FLIMbox card.
AB  - The phasor approach to FLIM (Fluorescence Lifetime Imaging Microscopy) is
      becoming popular due to the powerful fit free analysis and the visualization of
      the decay at each point in images of cells and tissues. However, although several
      implementation of the method are offered by manufactures of FLIM accessories for
      microscopes, the details of the conversion of the decay to phasors at each point
      in an image requires some consideration. Here, we show that if the decay is not
      properly acquired, the apparently simple phasor transformation can provide
      incorrect phasor plots and the results may be misinterpreted. In particular, we
      show the disagreement in experimental data acquired on the same samples using the
      two cards (FLIMbox, frequency domain and Becker & Hickl BH 830, time domain) and
      the effect produced by using the BH 830 card with different settings. This
      difference in data acquisition translates to the assignment of phasor components
      calculated using different acquisition parameters. This effect is already present
      in the original data that are not acquired with the proper parameters for the
      phasor conversion. We also show that the difference in the resolution of
      components already exists in the data acquired in the time domain when used with
      settings that do not allow acquisition of the fluorescence decay on a sufficient
      large time scale. RESEARCH HIGHLIGHTS: This paper is intended to made researchers
      aware of some simple requirements for the conversion of time-domain data
      (typically TCSPC) to phasors. The use of phasors for FLIM analysis has seen a
      surge of popularity. Since the phasor approach is a fit free method and has a
      powerful visualization of the data, it appears very simple to use. This paper
      shows that when the original data in the time domain is not acquired with the
      proper time range to cover the lifetimes in a sample, the conversion to phasors
      can produce very erroneous results. These results are appearing more frequently
      in the literature since many of the manufacturers of FLIM accessories for
      microscopes are now offering the phasor analysis in their software. Here, we show
      that the phasor transformation per se cannot correct for the problems with data
      acquisition and that one is misled to think that the "phasor approach" is a
      universal fix for the lack of the proper time range for data acquisition.

PMID- 30295348
TI  - Abnormal Hippocampal Subfields May Be Potential Predictors of Worse Early
      Response to Antidepressant Treatment in Drug-Naive Patients With Major Depressive
      Disorder.
AB  - BACKGROUND: Previous studies had proved that hippocampal volume has predictive
      value for antidepressant response in patients with major depressive disorder
      (MDD). However, the exact subregion of the hippocampus relevant to the predictive
      role of antidepressants response is not known. PURPOSE: To explore which
      hippocampal subfield volumes might predict an early response to first-time use of
      antidepressants in drug-naive MDD patients. STUDY TYPE: Prospective. POPULATION:
      Thirty-eight drug-naive MDD patients (mean illness duration = 1.6 years) and 55
      healthy control subjects (HCS). FIELD STRENGTH/SEQUENCE: 3.0T MRI, T1 -weighted,
      3D, SPGR sequence. ASSESSMENT: The hippocampal subfields and total intracranial
      volume were measured with FreeSurfer. The response to antidepressants was
      evaluated by the reduction rate of the Hamilton Rating Scale for Depression score
      (RRS) after a 6-week routine clinical antidepressant treatment. STATISTICAL
      TESTS: The relationship between hippocampal subfield volumes and RRS was explored
      using partial correlation analysis. Volume differences among early responding
      patients (ERP), nonresponding patients (NRP), and HCS were examined by
      multivariate analysis of covariance. Receiver operating characteristic (ROC)
      curve analysis was used to evaluate the sensitivity and specificity of volumes as
      predictors. RESULTS: NRP had significantly larger volumes than both ERP and HCS
      in bilateral subiculum, cornu ammonis (CA) 1 and left CA2/3, CA4/dentate gyrus
      (DG) (all P < 0.01, false discovery rate corrected). Significant negative
      correlations were found between the RRS and volumes of left subiculum (P =
      0.004), CA2/3 (P = 0.008), and CA4/DG (P = 0.004) in the whole MDD group. ROC
      analysis demonstrated that the left subiculum exhibited the highest accuracy for
      differentiating NRP from ERP, with a sensitivity of 76.9% and specificity of 80%.
      DATA CONCLUSION: These findings propose that volumes of certain hippocampal
      subfields may be associated with antidepressant treatment and this has potential
      use in clinical applications for treatment selection in patients with MDD at an
      early stage. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 4 J. Magn. Reson.
      Imaging 2018.

PMID- 30295350
TI  - Exploring Rigid and Flexible Core Trivalent Sialosides for Influenza Virus
      Inhibition.
AB  - Herein, the chemical synthesis and binding analysis of functionalizable rigid and
      flexible core trivalent sialosides bearing oligoethylene glycol (OEG) spacers
      interacting with spike proteins of influenza A virus (IAV) X31 is described.
      Although the flexible Tris-based trivalent sialosides achieved micromolar binding
      constants, a trivalent binder based on a rigid adamantane core dominated flexible
      tripodal compounds with micromolar binding and hemagglutination inhibition
      constants. Simulation studies indicated increased conformational penalties for
      long OEG spacers. Using a systematic approach with molecular modeling and
      simulations as well as biophysical analysis, these findings emphasize on the
      importance of the scaffold rigidity and the challenges associated with the spacer
      length optimization.

PMID- 30295349
TI  - Spatial object recognition memory formation under acute stress.
AB  - Stress is known to have a critical impact on memory processes. In the present
      work, we focus on the effects of an acute stress event closely associated to an
      unrelated learning task. Here we show that acute stress (elevated platform
      session, EP) experienced one hour after a weak spatial object recognition
      training (SOR), which only induces a short-term memory (STM), promoted the
      formation of SOR-long term memory (SOR-LTM) in rats. The effect induced by stress
      was dependent on the activation of glucocorticoid- and mineralocorticoid
      receptors, brain-derived neurotrophic factor (BDNF) and protein synthesis in the
      dorsal hippocampus. In contrast, EP after a strong SOR impaired SOR-LTM probably
      by interfering with the use of necessary resources. Moreover, we show that the EP
      session before training induced anterograde interference, which it was not
      reversed by a subsequent exposure to an open field. Our findings provide novel
      insights into the impact of stress on LTM formation in rodents and they are
      discussed under the behavioral analogue of the synaptic tagging and capture
      hypothesis. This article is protected by copyright. All rights reserved.

PMID- 30295351
TI  - Clusterin contributes to early stage of Alzheimer's disease pathogenesis.
AB  - While clusterin is reportedly involved in Alzheimer's disease (AD) pathogenesis,
      how clusterin interacts with amyloid-beta (Abeta) to cause Abeta neurotoxicity
      remains unclear in vivo. Using 5*FAD transgenic mice, which develop robust AD
      pathology and memory deficits when very young, we detected interactions between
      clusterin and Abeta in the mouse brains. The two proteins were concurrently
      upregulated and bound or colocalized with each other in the same complexes or in
      amyloid plaques. Neuropathology and cognitive performance were assessed in the
      progeny of clusterin-null mice crossed with 5*FAD mice, yielding clu-/- ;5*FAD
      and clu+/+ ;5*FAD. We found far less of the various pools of Abeta proteins, most
      strikingly soluble Abeta oligomers and amyloid plaques in clu-/- ;5*FAD mice at 5
      months of age. At that age, those mice also had higher levels of neuronal and
      synaptic proteins and better motor coordination, spatial learning and memory than
      age-matched clu+/+ ;5*FAD mice. However, at 10 months of age, these differences
      disappeared, with Abeta and plaque deposition, neuronal and synaptic proteins and
      impairment of behavioral and cognitive performance similar in both groups. These
      findings demonstrate that clusterin is necessarily involved in early stages of AD
      pathogenesis by enhancing toxic Abeta pools to cause Abeta-directed
      neurodegeneration and behavioral and cognitive impairments, but not in late
      stage.

PMID- 30295347
TI  - KCTD7 deficiency defines a distinct neurodegenerative disorder with a conserved
      autophagy-lysosome defect.
AB  - OBJECTIVE: Several small case series identified KCTD7 mutations in patients with
      a rare autosomal recessive disorder designated progressive myoclonic epilepsy
      (EPM3) and neuronal ceroid lipofuscinosis (CLN14). Despite the name KCTD
      (potassium channel tetramerization domain), KCTD protein family members lack
      predicted channel domains. We sought to translate insight gained from yeast
      studies to uncover disease mechanisms associated with deficiencies in KCTD7 of
      unknown function. METHODS: Novel KCTD7 variants in new and published patients
      were assessed for disease causality using genetic analyses, cell-based functional
      assays of patient fibroblasts and knockout yeast, and electron microscopy of
      patient samples. RESULTS: Patients with KCTD7 mutations can exhibit movement
      disorders or developmental regression before seizure onset, and are distinguished
      from similar disorders by an earlier age of onset. Although most published KCTD7
      patient variants were excluded from a genome sequence database of normal human
      variations, most newly identified patient variants are present in this database,
      potentially challenging disease causality. However, genetic analysis and impaired
      biochemical interactions with cullin 3 support a causal role for patient KCTD7
      variants, suggesting deleterious alleles of KCTD7 and other rare disease variants
      may be underestimated. Both patient-derived fibroblasts and yeast lacking Whi2
      with sequence similarity to KCTD7 have impaired autophagy consistent with brain
      pathology. INTERPRETATION: Biallelic KCTD7 mutations define a neurodegenerative
      disorder with lipofuscin and lipid droplet accumulation but without defining
      features of neuronal ceroid lipofuscinosis or lysosomal storage disorders. KCTD7
      deficiency appears to cause an underlying autophagy-lysosome defect conserved in
      yeast, thereby assigning a biological role for KCTD7. Ann Neurol 2018;84:774-788.

PMID- 30295352
TI  - Rho and Rac, but not ROCK, are required for secretion of human and mouse
      eosinophil-associated RNases.
AB  - BACKGROUND: Eosinophil-associated RNases (EARs) are stored preformed in
      eosinophil cytoplasmic secretory granules and have a key role in eosinophil
      effector functions in host defence and inflammatory disorders. However, the
      secretion mechanisms of EARs are poorly understood. OBJECTIVE: Our study aimed to
      understand the involvement of cytoskeleton machinery in EAR secretion. METHODS:
      Fresh human and mouse eosinophils were stimulated with CCL11, and the secretion
      of enzymatically active EARs was detected using an RNase activity assay. The
      involvement of cytoskeletal elements or microtubules was probed using specific
      inhibitors. RESULTS: We found that dynamic polymerization of microtubules and
      cytoskeletal elements, such as Rho and Rac, is required for chemokine-mediated
      EAR secretion from human and mouse eosinophils. However, inhibition of ROCK (Rho
      associated protein kinase) increased EAR secretion in human and mouse eosinophils
      even in the absence of chemokine stimulation, suggesting ROCK negatively
      regulates EAR secretion. CONCLUSIONS: Collectively, these data suggest a
      cytoskeleton-dependent mechanism of EAR secretion from eosinophils, findings that
      are pertinent to host defence, allergy and other eosinophil-associated diseases.

PMID- 30295353
TI  - Video polysomnographic findings in non-rapid eye movement parasomnia.
AB  - Although video polysomnography (vPSG) is not routinely recommended for the
      evaluation of typical cases of non-rapid eye movement (NREM) parasomnias, it can
      aid diagnosis of unusual cases, other sleep disorders and complicated cases with
      REM behaviour disorder (RBD), and in differentiating parasomnias from epilepsy.
      In this study, we aimed to assess vPSG findings in consecutive patients with a
      clinical diagnosis of NREM-parasomnia covering the whole phenotypic spectrum.
      Five hundred and twelve patients with a final diagnosis of NREM parasomnia who
      had undergone vPSG were retrospectively identified. vPSGs were analysed for
      features of NREM parasomnia and for the presence of other sleep disorders. Two
      hundred and six (40.0%) patients were clinically diagnosed with sleepwalking, 72
      (14.1%) with sleep terrors, 39 (7.6%) with confusional arousals, 15 (2.9%) with
      sexsomnia, seven (1.4%) with sleep-related eating disorder, 122 (23.8%) with
      mixed phenotype, and 51 (10.0%) with parasomnia overlap disorder (POD). The vPSG
      supported the diagnosis of NREM parasomnia in 64.4% of the patients and of POD in
      98%. In 28.9% of the patients, obstructive sleep apnea (OSA) or/and periodic limb
      movements during sleep (PLMS) were identified, most commonly in older, male,
      sleepy and obese patients. vPSG has a high diagnostic yield in patients with NREM
      parasomnia and should be routinely performed when there is diagnostic doubt, or
      in patients where there is a suspicion of OSA and PLMS.

PMID- 30295354
TI  - Enamel sample preparation for AFM: Influence on roughness and morphology.
AB  - Human dental enamel is organized by prisms that are structured between 3 and 6 um
      in diameter. Determining the relationships between different treatments on the
      surface of enamel using ultrastructural analysis is the purpose of many in vitro
      experiments. Different sample pretreatments have been reported in the literature.
      Grinding and polishing are common procedures for enamel preparation. They provide
      a flat and standardized surface, which is imperative for the use of some
      techniques such as ATR-FTIR. However, for morphological analysis, SEM and AFM
      represent easier methods to measure and reduce the biological sample variation.
      Therefore, the objective of this study was to establish how different forms of
      enamel preparation can influence the advent of artifacts during ultrastructural
      observation, especially by AFM analysis. Four groups (n = 10) were tested: (a)
      without preparation; (b) polishing with a diamond paste; (c) grinding with
      decreasing granulations of silicon carbide papers; (d) grinding with polishing.
      Images were obtained using the Peak-Force Tapping mode. After the first images
      were obtained, all fragments were acid etched with 37% phosphoric acid for 30
      seconds, rinsed for 60 seconds, and dried intensively. Upon grinding and
      polishing, the exposure of the inner enamel surfaces provided a less mineralized
      layer that was marked by scratches and a higher susceptibility to treatments.
      Moreover, using native enamel provided more valuable information on the surface
      and the roughness changes for clinical applications. In addition, phosphoric acid
      is an option for observing the prismatic arrangement after grinding and/or
      polishing changes the morphology. RESEARCH HIGHLIGHTS: The use of native enamel
      samples to investigate the effects of different treatments on surface should be
      preferred in research, when the technique allows it.

PMID- 30295355
TI  - Quantification of crystallinity using zero-loss filtered electron diffraction.
AB  - : The quantity of the crystalline phases present in a nanomaterial is an
      important parameter that governs the correlation between its properties and
      microstructure. However, quantification of crystallinity in nanoscale-level
      applications by conventional methods (Raman spectroscopy and X-ray diffraction)
      is difficult because of the spatial limitations of sampling. Therefore, we
      propose a technique that involves using energy-filtered electron diffraction in
      transmission electron microscopy which offers improved spatial resolution. The
      degree of crystallinity (DOC) was calculated by separating the crystalline and
      amorphous intensities from the total intensity histogram acquired by the
      azimuthal averaging of the zero-loss filtered signals from electron diffraction.
      In order to validate the method, it was demonstrated that the DOC calculated by
      zero-loss filtered electron diffraction was consistent with the DOC measured by
      the area ratio using an amorphous silicon on crystalline silicon standard sample.
      In addition, the results obtained from zero-loss filtered and conventional
      electron diffractions were compared. The zero-loss filtered electron diffraction
      successfully provided the reliable results of the crystallinity quantification.
      In contrast, the DOC measured using conventional electron diffraction yielded
      extremely variable results. Therefore, our results provide a crystallinity
      quantification technique that can extract quantitative information about
      crystallinity of nanoscale devices by using zero-loss filtered electron
      diffraction with better reliability than conventional electron diffraction.
      RESEARCH HIGHLIGHTS: The degree of crystallinity can be measured by separating
      the crystalline and amorphous intensities from the total intensity histogram
      acquired by the azimuthal averaging of the zero-loss filtered signals from
      selected area electron diffraction.

PMID- 30295356
TI  - Switching of Monomer Fluorescence, Charge-Transfer Fluorescence, and Room
      Temperature Phosphorescence Induced by Aromatic Guest Inclusion in a
      Supramolecular Host.
AB  - Crystal engineering of three-component crystals with guest-dependent
      photoluminescence switching, including (i) crystallization-induced emission
      enhancement, (ii) intermolecular charge-transfer emission, and (iii) room
      temperature phosphorescence under ultraviolet irradiation, was demonstrated. This
      strategy was based on the confinement of aromatic guests in a supramolecular host
      (denoted as EBPDI-TPFB) composed of 5,5'-(ethyne-1,2-diyl)bis(2-pyridin-3-yl
      isoindoline-1,3-dione (EBPDI) with two tris(pentafluorophenyl)borane (TPFB)
      molecules linked by B-N dative bonds that acted as Lewis pairs. The single
      crystal X-ray structures of complexes with eight different guests were collected,
      revealing that the size and/or shape of the supramolecular host EBPDI-TPFB was
      modulated by the included guest molecules. The excellent guest inclusion ability
      of EBPDI-TPFB allowed systematic photoluminescence regulation of the complexes,
      which exhibited multicolor emissions in the crystalline state. Photoluminescence
      switching characteristics of the complexes were observed upon removing the guests
      or mechanical grinding of the crystals. These results indicated that using the
      host-guest chemistry of multicomponent crystals not only facilitates
      crystallization, but also can reveal hidden optical functions by combining
      molecules of interest, which should contribute to the fields of physical
      chemistry and materials science.

PMID- 30295357
TI  - Dilutional coagulopathy in pediatric scoliosis surgery: A single center report.
AB  - BACKGROUND: Children undergoing posterior spinal fusion experience high blood
      loss often necessitating transfusion. An appropriately activated coagulation
      system provides hemostasis during surgery, but pathologic dysregulation can cause
      progressive bleeding and increased transfusions. Despite receiving
      antifibrinolytics for clot stabilization, many patients still require
      transfusions. AIMS: We sought to examine the association of dilutional
      coagulopathy with blood loss and blood transfusion in posterior spinal fusion for
      pediatric scoliosis patients. METHODS: A retrospective, single institution study
      of children undergoing posterior spinal fusion >6 levels with a standardized,
      prospective anesthetic protocol utilizing antifibrinolytics. Blood loss was
      evaluated using a hematocrit-based calculation. To evaluate transfusions, a
      normalized Blood Product Transfusion calculation was developed. Factors
      associated with blood loss and blood transfusions were determined by univariate
      analysis and multivariate regression modeling with multicollinearity and
      mediation analysis. RESULTS: Patients received 73.7 mL/kg (standard deviation +/
      30.8) of fluid poor in coagulation factors. Estimated blood loss was 42.6 mL/kg
      (standard deviation +/-18.0). There was a significant association between
      estimated blood loss and total fluids delivered (Spearman's rho = 0.51, 95%
      confidence interval 0.33-0.65, P < 0.001). Factors significantly associated with
      normalized Blood Product Transfusion in this cohort included age, weight,
      scoliosis type, levels fused, total osteotomies, pelvic fixation, total fluid,
      maximum prothrombin time, and minimum fibrinogen. Regression modeling showed the
      best combination of variables for modeling normalized Blood Product Transfusion
      included patient weight, number of levels fused, total fluid administered, and
      maximum prothrombin time. CONCLUSION: Blood product transfusion remains a
      frustrating problem in pediatric scoliosis. Identifying and controlling
      dilutional coagulopathy in these patients may reduce blood loss and the need for
      blood transfusion.

PMID- 30295358
TI  - Electrical Stimulation of the Anterior Thalamus for Epilepsy: Clinical Outcome
      and Analysis of Efficient Target.
AB  - OBJECTIVE: Deep brain stimulation (DBS) of the anterior thalamic complex (ANT) is
      an adjunctive therapy for pharmacoresistant epilepsy. To define the most
      efficient target in DBS for epilepsy, we investigate clinical data, position of
      leads, usability of atlas data compared to electric field modeling based on
      programming parameters. METHODS: Data from ten consecutive patients who underwent
      ANT-DBS were analyzed. The mammillothalamic tract (MTT), an internal landmark for
      direct stereotactic targeting, was segmented from MRI. Centers of stimulation
      were determined and their positions relative to ventricles and the MTT were
      analyzed. Two 3D thalamus atlases were transformed to segmented patient's thalami
      and proportions of activated nuclei were calculated. RESULTS: Our data indicate
      higher response rates with a center of stimulation 5 mm lateral to the wall of
      the third ventricle (R2 for reduction of focal seizure frequency and distance to
      the wall of the third ventricle = 0.48, p = 0.026). For reduction of focal
      seizures, a strong positive correlation with the dorsal distance to the
      midcommissural plane was found (R2 = 0.66, p = 0.004). In one 3D atlas,
      stimulation of internal medullary lamina (IML) correlated strongly positive with
      response rates, which, however, did not reach statistical significance (R2 =
      0.69, p = 0.17 for tonic-clonic seizures). All electrical fields covered the
      diameter of the MTT. The position of the MTT in the thalamus was highly variable
      (range: x-coordinate 4.0 to 7.3 mm, y-coordinate -1.3 to 5.1 mm in AC-PC space).
      CONCLUSIONS: The distance of the active contact to the lateral wall of the third
      ventricle, MTT and the ventrodorsal distance to midcommissural plane appear to be
      relevant for optimal target planning. For reduction of focal seizure frequency,
      we found best response rates with a center of stimulation 5 mm lateral to the
      wall of the third ventricle, and a lead tip 10 mm dorsal of the midcommissural
      plane.

PMID- 30295359
TI  - Anesthesia in children with osteogenesis imperfecta: Retrospective chart review
      of 83 patients and 205 anesthetics over 7 years.
AB  - BACKGROUND: Osteogenesis imperfecta is the collective term for a heterogeneous
      group of connective tissue syndromes characterized by bone fragility with
      multisystem involvement and perioperative implications. AIMS: Literature review
      of anesthetic management of patients with osteogenesis imperfecta revealed a
      paucity of data on the incidence of perioperative challenges. We sought to
      determine the rates of these challenges in our study cohort. METHODS: Data were
      collected in a specialty orthopedic hospital from 2008 to 2015 for 83
      osteogenesis imperfecta patients undergoing 205 surgeries: 203 orthopedic
      surgeries and 2 mid-face reconstructive surgeries. Airway management, intravenous
      access, surgical blood loss, use of peripheral nerve blockade and/or neuraxial
      techniques, presence of perioperative fracture, and peak intraoperative
      temperature were evaluated and analyzed. RESULTS: Difficult airway was
      encountered in 3/205 (1.5%) cases and perioperative fracture in 2/205 (1%) cases.
      Neuraxial anesthesia was attempted in 64/205 cases with an 87.5% success rate.
      All peripheral nerve block attempts (33/205 cases) were successful. Difficult
      intravenous catheter placement was noted in 8/205 (4%) cases. Estimated blood
      loss >10% of estimated blood volume was considered significant, and occurred in
      35/205 (17%) cases. Significant blood loss occurred more often in severe
      osteogenesis imperfecta types: 18/76 (23.7%) in Type III and 11/65 (16.9%) in
      Type IV, whereas only 4/47 (8.5%) occurred in mild Type I. In our 205 case
      cohort, osteogenesis imperfecta Type III had 5.6 times the odds [(95% CI = 1.8
      17.2) P = 0.003] of having an anesthetic complication as compared to osteogenesis
      imperfecta Type I. CONCLUSION: Patients with osteogenesis imperfecta undergo
      frequent anesthetic exposures, but anesthetic challenges in our series were
      uncommon. Odds of challenges are greater in severe osteogenesis imperfecta Type
      III, with significant blood loss and difficulty placing intravenous catheters
      more likely encountered in the more severe types.

PMID- 30295360
TI  - Targeting reactive oxygen species for respiratory infection: Fact or fancy?

PMID- 30295361
TI  - A simplified method of preparation of mammalian intestine samples for scanning
      electron microscopy.
AB  - Due to strong tissue hydration and complex architecture of the mucous membrane,
      appropriate preparation of inhomogeneous gastrointestinal tissues, especially
      from the intestine, for scanning electron microscopy is still a challenge and
      requires constant improvement of preparation techniques. In this article, we
      describe a simplified method of preparation of small intestinal mucosa tissues
      for observations in a scanning electron microscope. We emphasized the most
      important points in the preparation process that, when ignored, may result in
      formation of numerous artifacts and the inability to analyze the samples
      reliably. The developed technique facilitates proper animal tissue sampling in
      the field conditions, reducing the time of tissue collection and sample
      preparation as well as the total process costs. The fixative of choice, that is,
      buffered formalin, fixes, and stiffens the processed tissues properly, which is
      especially important in preservation of long, highly hydrated intestinal villi
      without shrinkage artifacts. The method described has been successfully used in
      comparative studies of the development of small intestines in mammals (pigs,
      mice, rats), reptiles, and birds (hens).

PMID- 30295362
TI  - Histomorphometry of ectopic mineralization using undecalcified frozen bone
      sections.
AB  - To investigate the correlation between mineral formation and enhanced expressions
      of some proteins using undecalcified frozen bone sections. Histological studies
      have revealed that some proteins, such as BMP2, BMPR1A, and Connexin 43, are
      expressed in and around sites of ectopic ossification. However, the relationship
      between the expressed proteins considered to be associated with the ossification
      and mineral formation in vivo is not clear. Ectonucleotide pyrophosphatase
      phosphodiesterase 1 (ENPP1)-mutant spinal hyperostotic TWY mice and ICR mice as
      controls were euthanized after calcein labeling, and undecalcified frozen
      sections were obtained from the middle thoracic spine. Intervertebral disc areas
      were examined histologically and by measuring calcein-labeled areas and areas
      showing immunoreactivity for BMP2, BMPR1A, and Connexin 43. Calcein-labeled
      areas, indicating mineralization in the ectopic mineralization sites, were
      significantly larger in the mutant mice than in controls. The expression of
      Connexin 43 was elevated in the annulus fibrosus. Increases in the calcein
      labeled areas was not correlated with increases in the areas showing
      immunoreactivity for Connexin 43 in the annulus fibrosus. There was no
      statistical correlation between enhanced immunohistochemical expression and
      elevated calcein-labeled areas. By applying the morphometrical analysis method
      using undecalcified frozen sections to ENPP1-mutant mice, quantitative evaluation
      of the mineralization and proteins expressed in the surrounding area in the same
      animal became possible.

PMID- 30295363
TI  - An electron microscopy three-dimensional characterization of titania nanotubes.
AB  - : To characterize complex, three-dimensional nanostructures, modern microscopy
      techniques are needed, such as electron tomography and focused ion beam (FIB)
      sectioning. The aim of this study was to apply these two techniques to
      characterize TiO2 nanotubes in terms of their size, shape, volume, porosity,
      geometric surface area, and specific surface area (SSA). For these experiments,
      titania nanotubes were fabricated by means of the electrochemical oxidation of
      titanium at a voltage of 20 V for 2 hr followed by heat treatment at 450 degrees
      C for 3 hr to change the amorphous structure into a crystalline anatase
      structure. The quantitative data obtained from the FIB and electron tomography
      reconstructions show a high similarity in porosity and some differences in SSA.
      These might be the result of differences in resolution between the two
      reconstruction techniques. RESEARCH HIGHLIGHTS: The resolution of electron
      tomography method is better than FIB sectioning that might influence on
      quantitative data like SSA. FIB sectioning allows to visualize 3D structure of
      much larger volume than electron tomography method. FIB sectioning and electron
      tomography are complementary techniques for characterizing nanostructured
      materials such as nanotube layers.

PMID- 30295364
TI  - Morphological evaluation of liposomal iron carriers.
AB  - Iron is one of the most important elements for human, because it plays an
      essential role in many metabolic processes. However, it is also recognized to be
      dangerous for its detrimental effect inside human cells, where, in the absence of
      homeostatic balance, it can induce free radicals formation. Moreover, an
      excessive accumulation of iron in tissues can produce iron overload, a condition
      incompatible with life. The use of liposomes as carriers can represent an
      interesting iron therapy to improve iron bioavailability and reduce its negative
      effects, in particular during pregnancy. In this study, a morphological analysis
      has been performed on commercial liposome vesicles at various drying times, both
      in saline solution and in distilled water. Furthermore, to highlight their
      possible interaction or internalization in cells, liposomes have been
      administered to human hemopoietic U937 cells. Ultrastructural analyses confirm
      that vesicle morphology and size are comparable with classical liposomal
      structures. Products are stable during specimen preparation and drying.
      Additionally, they have a good ability to penetrate into cells, interacting with
      cytoplasmic organelles, without inducing, at least apparently, any
      ultrastructural damage.

PMID- 30295365
TI  - Surface characteristics of a modified acidulated phosphate fluoride gel with nano
      hydroxyapatite coating applied on bovine enamel subjected to an erosive
      environment.
AB  - This study evaluated the antierosive effect applying a modified acidulated
      phosphate fluoride (APF) gel containing nano-hydroxyapatite (nHAp) on the enamel
      surface before erosion. After polishing, the exposed flat enamel surfaces (n =
      7/group) from bovine incisors were treated with artificial saliva (S - negative
      control), orange juice (ERO), APF gel (positive control) and APF_nHAp gel. All
      samples were subjected to six cycles of demineralization (orange juice, pH ~ 3.5,
      10 min) followed by remineralization (saliva, 37 degrees C, 1 hr). The enamel
      surface morphology, topography, and inorganic composition were analyzed using
      scanning electron microscopy, roughness testing, and micro energy-dispersive X
      ray fluorescence spectrometry, respectively. The mean (standard deviation)
      roughness values (Ra, MUm) were S, 0.13 (0.05); ERO, 0.25 (0.07); APF, 0.22
      (0.08); and APF_nHAp, 0.17 (0.04). Ra values were significantly higher after ERO
      (p < .01) and APF (p < .05) treatments than after S. The enamel surface
      morphology was altered by the treatments, except for the S specimens. The mineral
      content of the enamel showed a clear trend with Ca and P reduction in the order
      of APF < S < APF_nHAp < ERO and APF < S < ERO < APF_nHAp, respectively. We can
      conclude that APF gel increased mineral concentration on the enamel. Moreover,
      the APF_nHAp material modified the composition and morphology of the enamel
      surface.

PMID- 30295366
TI  - Morphological evaluation of the liver in Wistar rats inoculated with
      Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae) salivary gland
      extracts.
AB  - The Rhipicephalus sanguineus is considered a species of medical and veterinary
      importance. The feeding process of these animals occurs due to the combined
      action of their mouthparts and the saliva produced by the salivary glands, vital
      organs for the biological success of the ticks. In addition, these glands act as
      storage sites for the pathogens transmitted to the host through the inoculation
      of the saliva. In this sense, the present study had the objective to analyze the
      behavior of male Wistar rat hepatic cells submitted to in vivo application of the
      salivary gland extract (SGE) obtained from R. sanguineus female ticks. The study
      involved five groups (four male adults each): CG (non-inoculated individuals);
      PBS1 (one phosphate buffer saline injection); PBS2 (two PBS injections); SGE1
      (one injection of SGE at 0.04 MUg/MUL) and SGE2 (two injections of SGE at 0.04
      MUg/MUL). After the exposures, the livers were removed and submitted to the
      following histological and histochemical stains: HE, toluidine blue, Xylidine
      Ponceau, alcian blue/PAS, and osmium-imidazole. The results showed that both the
      PBS and the SGE caused hepatic moderate alterations, such as: (a) emergence of
      lipid plaques among the hepatic cords; (b) cytoplasmic vacuolation of the hepatic
      cells; (c) hepatocytes showing pyknotic nuclei; (d) presence of homogeneous or
      granular secretion in the cytoplasm of the hepatocytes. Despite the slight
      morphological alterations observed in the hepatic cells and tissue, the latter
      did not show signs of disorganization after the exposure to the extracts.

PMID- 30295367
TI  - Evaluation of cell proliferation in cystic lesions associated with impacted third
      molars.
AB  - The purpose of this study was to evaluate the metabolism and epithelial cell
      proliferation of odontogenic keratocyst (OKC), dentigerous cyst (DC), and
      unicystic ameloblastoma (UA) by quantifying the nucleolar organizing regions
      (AgNORs) and Ki-67 protein immunoexpression. Forty-eight cases (16 OKC, 16 DC,
      and 16 UA) were evaluated retrospectively. The metabolism and epithelial cell
      proliferation was measured by the Ki-67 positive cell percentage index and by the
      mean AgNOR count in each group. The Ki-67 and AgNOR counts were significantly
      higher in OKC comparing to the DC and UA (p < .001). Ki-67 positive cells were
      observed higher in suprabasal cell layers of OKC with uniform distribution, a few
      of them were predominantly observed in basal cell layer in DC and UA. The AgNOR
      count was significantly higher in the OKC basal cell layers and observed
      throughout the lining epithelium of DC and UA. Ki-67 and AgNOR reinforced the
      aggressive character of OKC, presenting high metabolism and cellular
      proliferation compared to DC and UA, possibly due to its more aggressive clinical
      behavior and high recurrence rate.

PMID- 30295368
TI  - Field Distribution of Transcranial Static Magnetic Stimulation in Realistic Human
      Head Model.

PMID- 30295369
TI  - A Prosthesis Retention System for Full-Arch, Fixed, Implant-Supported Prosthesis.
AB  - Full-arch, fixed, implant-supported prostheses can be designed to be cement- or
      screw-retained. Both retention mechanisms have a few inherent disadvantages. A
      fixed attachment system has been introduced to circumvent the disadvantages of
      both screw and cement retention. This system eliminates the screw access holes
      and the use of cement. The number of intraoral procedures required is also
      reduced. The purpose of this article is to report a case using the Locator F-Tx
      Attachment System to facilitate fabrication of an esthetic, clinician
      retrievable, full-arch implant-supported fixed dental prosthesis.

PMID- 30295371
TI  - A novel dynamic opto-thermo-mechanical stress testing device 2: In situ
      stretching process of polymeric fibers.
AB  - In this article, we used the opto-mechanical stress testing-device to stretch a
      monofilament of isotactic Polypropylene, iPP, fibers. This device was used to
      obtain the mechanical behavior of these fibers by measuring the complete stress
      strain curves at different stretching conditions. Using this device, the
      different regions of iPP fiber where the mechanical deformation takes place was
      characterized, including the necking region and fracture initiation process. The
      obtained mechanical behavior of iPP fibers was correlated to the variations of
      different optical parameters by attaching the device with the Pluta polarizing
      interference microscope. This microscope and the stress device allowed us to
      simultaneously measure the optical parameters and stress-strain data during
      stretching process at different stretching speeds. These data provide us with
      comprehensive information on the opto-mechanical behavior of polymeric fibers.
      Interferograms are included for illustration.

PMID- 30295370
TI  - A Pilot Study to Determine the Effect of Three Months of Oral Appliance Therapy
      using a Mandibular Advancement Device on HbA1c in Subjects with Type 2 Diabetes
      Mellitus and Obstructive Sleep Apnea.
AB  - PURPOSE: Continuous positive air pressure (CPAP) is recommended for obstructive
      sleep apnea (OSA) with type 2 diabetes mellitus (T2DM) but cost and compliance
      are major barriers. A mandibular advancement device (MAD) may be an economical,
      feasible alternative to CPAP. Various studies have been published to recommend
      MAD as an alternative to CPAP for OSA, but not regarding its efficacy for
      patients having OSA as well as T2DM. This study aims to objectively and
      subjectively evaluate oral appliance therapy using a MAD in patients having OSA
      as well as T2DM. MATERIALS AND METHODS: Patients who visited the hospital clinic
      having OSA as well as T2DM were recruited. After giving informed consent,
      participants were divided into three equally sized groups of three grades of OSA
      (mild, moderate, severe) on the basis of a polysomnography report and were given
      intervention of MAD at 50% of maximum mandibular protrusion and 20% of maximum
      interincisal opening. Objective outcomes were HbA1c level and apnea hypopnea
      index score (AHI). Subjective outcomes were Epworth Sleepiness Scale (ESS) and
      the Berlin Questionnaire. All outcomes were assessed before and after 3 months of
      intervention. RESULTS: A statistically significant difference was seen in all
      outcomes after intervention with MAD (p < 0.01) in all groups except HbA1c level
      in participants having severe OSA. CONCLUSION: MAD may be recommended in patients
      having OSA as well as T2DM. This study provides evidence to inform health care
      workers about possible use of MAD in OSA with T2DM.

PMID- 30295372
TI  - Irritating effects of sodium lauryl sulfate on human primary keratinocytes at
      subtoxic levels of exposure.
AB  - Chemical agents that can potentially cause skin irritation are typically tested
      in animal models or in vitro assays of cell viability or cytokine expression.
      However, these methods do not always provide translatable results and are not
      sufficiently sensitive for subtoxicity detection. Here, we introduce the
      mechanical properties of keratinocytes as novel endpoints for the safety
      assessment of chemical agents at the subtoxicity level. Human primary
      keratinocytes were treated with various concentrations of sodium lauryl sulfate
      (SLS) and their biological properties (proliferation, membrane integrity,
      inflammatory response, and morphology) were observed. Their biomechanical and
      geometrical parameters (stiffness and surface roughness) were also investigated
      by atomic force microscopy. Keratinocyte morphophysiological changes and
      inflammatory responses were significant at >=25 MUM SLS. The keratinocytes became
      less stiff due to changes in the distribution of F-actin filaments and alpha
      tubulin; these changes were significant even at lower doses of SLS (<=10 MUM).
      The morphophysiological changes of keratinocytes were clearly seen at a
      relatively high dose of SLS, while the mechanical properties of keratinocytes
      responded linearly to SLS at lower doses. Therefore, changes in mechanical
      properties can be used as new endpoints for in vitro toxicity testing with
      keratinocytes.

PMID- 30295375
TI  - Postural instability during attacks of migraine without aura.
AB  - BACKGROUND AND PURPOSE: Migraine has long been associated with unsteadiness and
      dizziness but postural control has not been studied in the ictal state. Here, the
      stability of upright stance during migraine attacks was measured. METHODS: Static
      balance was assessed prospectively in migraine patients (n = 30) during quiet
      stance for 40 s on a posturographic force platform. Recordings were performed
      both ictally and in the pain-free interval. Subjects were assessed under four
      different conditions yielding different visual and proprioceptive feedback
      environments. Both ictal and interictal data were compared with age-matched
      healthy controls (n = 30). RESULTS: Postural instability increased significantly
      under all experimental conditions during migraine attacks. Whilst standing on a
      foam pad with eyes closed, median sway area was 353 mm2 in control subjects, 318
      mm2 in migraineurs in the pain-free period and 618 mm2 in the ictal state.
      However, Romberg and vestibular Romberg quotients were not altered during
      migraine attacks. Spectral analyses of postural sway also showed similar profiles
      in migraineurs and controls. The severity of headache was inversely correlated to
      Romberg quotients. CONCLUSIONS: The demonstrated pattern of balance disorder
      during migraine attacks suggests a transient cerebellar dysfunction. Our findings
      also indicate that intense headache induces a re-weighting of sensory processing
      toward less dependence on visual and proprioceptive information.

PMID- 30295373
TI  - Morphological alterations in the ovaries of Amblyomma cajennense semi-engorged
      ticks exposed to ethanolic extract of Acmella oleracea.
AB  - The present study analyzed the effects of different concentrations of Acmella
      oleracea crude ethanolic extract (EEAO) on the development of germ cells from
      semi-engorged Amblyomma cajennense females in order to evaluate the potential of
      this natural chemical as a strategy to control these important ectoparasites. A
      hundred semi-engorged females were divided into five groups (duplicates) (10
      animals/group): Control 1 (distilled water); Control 2 (solvent ethanol 50% and
      DMSO 1%); and Treatment I to III (3.1, 6.2, and 12.5 mg/mL of EEAO,
      respectively). For the exposure of the ticks to the extract was used the Adult
      Immersion Test. After the exposition, the ovaries were removed and submitted to
      histological analysis using Harris hematoxylin and aqueous eosin. The
      histochemical tests were performed using PAS and Bromophenol blue staining
      techniques, for the detection of total polysaccharides and total protein,
      respectively. The extract caused significant alterations in the oocytes,
      including changes in the shape of the cells, disorganization, and cytoplasmic
      vacuolation, decrease in the number of yolk granules and germ vesicle
      fragmentation. These alterations were more intense in the oocytes in initial
      developmental stages (I and II). The results obtained in this study confirm the
      cytotoxic potential of the ethanolic extract of A. oleracea on the germ cells of
      A. cajennense females, opening up the possibility to use this extract as an
      alternative to control these ectoparasites.

PMID- 30295376
TI  - In-situ 2D bacterial crystal growth as a function of protein concentration: An
      atomic force microscopy study.
AB  - : The interplay between protein concentration and (observation) time has been
      investigated for the adsorption and crystal growth of the bacterial SbpA proteins
      on hydrophobic fluoride-functionalized SiO2 surfaces. For this purpose, atomic
      force microscopy (AFM) has been performed in real-time for monitoring protein
      crystal growth at different protein concentrations. Results reveal that (1)
      crystal formation occurs at concentrations above 0.08 uM and (2) the compliance
      of the formed crystal decreases by increasing protein concentration. All the
      crystal domains observed presented similar lattice parameters (being the mean
      value for the unit cell: a = 14.8 +/- 0.5 nm, b = 14.7 +/- 0.5 nm, gamma = 90 
      degrees  +/- 2). Protein film formation is shown to take place from initial
      nucleation points which originate a gradual and fast extension of the crystalline
      domains. The Avrami equation describes well the experimental results. Overall,
      the results suggest that protein-substrate interactions prevail over protein
      protein interactions. RESEARCH HIGHLIGHTS: AFM enables to monitor protein
      crystallization in real-time. AFM high-resolution determines lattice parameters
      and viscoelastic properties. S-layer crystal growth rate increases with protein
      concentration. Avrami equation models protein crystal growth.

PMID- 30295377
TI  - Ultrastructural description of fresh and frozen/thawed sperm derived from
      collared peccaries (Pecari tajacu Linnaeus, 1,758).
AB  - The aim was to describe, through scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM), the ultrastructure of peccaries' fresh
      and frozen-thawed sperm. For that, semen derived from three mature males was
      obtained by electroejaculation and evaluated for motility, membrane integrity,
      membrane functionality, chromatin integrity, and morphology through light
      microscopy. Samples were frozen using a Tris extender plus egg yolk (20%) and
      glycerol (6%). Then, fresh and frozen-thawed semen samples were mixed in
      different sperm pools that were processed for SEM and TEM. Sperm motility,
      membrane integrity, and functionality were impaired (p < .05) by freezing-thawing
      procedures, but sperm morphology, and chromatin integrity evaluated by light
      microscopy were not significantly affected. The SEM revealed that peccaries'
      sperm presents a flattened head in a paddle format, measuring 6.07 MUm in length
      and 3.84 MUm in width, with a vastus acrosome (4.46 MUm). Normal tails measure
      38.11 MUm, being formed by an extensive midpiece with 15.52 MUm in length. In
      frozen-thawed samples, both SEM and TEM provide us information about damage
      undetected through light microscopy as the presence of vesicles in the acrosome,
      loose plasma membrane, vacuolized mitochondria, dense fibers disorganized, and
      decondensed chromatin. In conclusion, we provide the first description of the
      sperm ultrasctruture in collared peccaries. Moreover, SEM and TEM help us to
      identify some nanometric damage provoked by freezing-thawing procedures, thus
      providing valuable information for the improvement of such important protocols
      used for biobanking formation.

PMID- 30295378
TI  - Long-term adalimumab treatment of hidradenitis suppurativa: Results and practical
      insights from a real-life experience.

PMID- 30295374
TI  - The Conometric Concept: A Two-Year Follow-Up of Fixed Partial CEREC Restorations
      Supported By Cone-In-Cone Abutments.
AB  - PURPOSE: To evaluate the performance of definitive, implant-supported, lithium
      disilicate fixed dental prostheses (LS2 FDPs) manufactured with a computer
      assisted design/computer-assisted manufacturing (CAD/CAM) system. All patients
      received two-unit restorations placed in posterior regions, supported by
      osseointegrated implants with cone-in-cone connection abutments. MATERIALS AND
      METHODS: Two implants (Ankylos) were placed into healed sites or fresh extraction
      sockets in the maxillary/mandibular posterior regions of partially edentulous
      patients. Definitive digital impressions were made 3 months after surgery. Twenty
      four patients received fixed  monolithic LS2 restorations manufactured with the
      CEREC system. All restorations were connected to the implants using cone-in-cone
      connection abutments. Peri-implant pocket depths were recorded for 2 years at
      each follow-up visit. Esthetic, functional, and biologic United States Public
      Health Services (USPHS) parameters modified by the FDI World Dental Federation
      study design were assessed yearly until the last follow-up appointment. The
      opposing dentitions were identified by type of restoration and supporting
      structures at the time of placement of the definitive restorations and at the 2
      year follow-up visits. RESULTS: One patient (4.16%) moved to an unknown location
      during the study. A total of 23 FDPs (95.8%) supported by 46 implants reached the
      2-year follow-up. None of the prostheses failed, or became loose or detached. No
      significant difference involving probing levels between the experimental times
      were found. CONCLUSIONS: The results of this research indicated that the abutment
      prostheses connection using a cone-in-cone approach was successful within the 2
      year period of this study. None of the studied monolithic LS2 glass-ceramic
      prostheses milled using the CEREC CAD/CAM system fractured or became detached.

PMID- 30295380
TI  - A patient with delusional infestation by proxy: Issues for vulnerable adults.
AB  - A 57-year-old Caucasian female presented to our clinic with her 23-year-old son,
      who was profoundly autistic. Our patient was convinced that her son had an
      infestation with fibers and believed that he had developed the condition as a
      young child. She described the symptoms of the infestation in her son's skin on
      his behalf, as he was not able to communicate. She identified dietary factors as
      a causative factor and wanted them removed from his diet. Her son had seborrhoeic
      dermatitis on examination, with no evidence of an infestation. Our patient later
      identified that fibers were coming out of her skin also. Her medical history
      included a road traffic accident resulting in back pain. Blood, urine, and
      microbiological investigations were normal. She was diagnosed with delusional
      infestation (DI) by proxy, and was started on risperidone. We present an
      interesting case of a patient with DI by proxy, in which the delusional beliefs
      of the mother have been projected onto her son. Issues of safeguarding vulnerable
      adults are raised in such cases, suggesting the crucial role of the physician in
      ensuring patient safety. DI by proxy has been reported in patients with children
      and animals, but we believe this is the first report of DI by proxy involving a
      vulnerable adult.

PMID- 30295379
TI  - Update of calcineurin inhibitors to treat inverse psoriasis: A systematic review.
AB  - Inverse psoriasis commonly involves skin fold areas including the axillae,
      perianal skin, intergluteal cleft, inframammary, genital/inguinal, abdominal, and
      retroauricular folds. Topical calcineurin inhibitors are indicated for the
      treatment of atopic dermatitis but have also been studied in the treatment of
      psoriasis. The object of the present study is to define the efficacy of topical
      calcineurin inhibitors in the treatment of psoriasis. We checked for English
      vernacular articles conveyed since 1990 in PubMed, Ovid/Cochrane, and Embase
      using "tacrolimus," "pimecrolimus," or "topical calcineurin inhibitors," and
      "psoriasis" as keywords. Eight double-blind studies and seven open studies
      displayed the ampleness of topical tacrolimus in psoriasis. Included studies
      demonstrated a considerable efficacy of topical administration of tacrolimus and
      pimecrolimus in the treatment of psoriasis, especially for facial, genital, and
      intertriginous areas. The role of topical tacrolimus and pimecrolimus in the
      treatment of psoriasis seems to be promising as shown by the results of double
      blind and open studies. Because these agents do not cause cutaneous atrophy, they
      have a special role in facial, genital, and intertriginous psoriatic lesions.
      Both agents await additional investigation to determine their roles.

PMID- 30295382
TI  - Penetrability of a new endodontic sealer: A confocal laser scanning microscopy
      evaluation.
AB  - : This study aimed to evaluate the penetration of a new endodontic sealer into
      the dentinal tubules. Twenty single-rooted teeth were selected. The crown was
      sectioned, and the canals were instrumented with a reciprocating system.
      Irrigation was performed with 2 mL of 2.5% sodium hypochlorite between each file
      change. After instrumentation, the root canals were irrigated with 2 mL of17%
      EDTA for 3 min followed by saline solution. The specimens were randomized into
      two groups (n =10) according to the endodontic sealer: AH Plus (AP) or Sealer
      Plus (SP). All specimens were filled using the lateral compaction technique.
      Rhodamine B dye (red) was incorporated to the sealers to provide the fluorescence
      which will enable confocal laser scanning microscopy (CLSM) assessment. The roots
      were sectioned 2, 4, and 6 mm from the apex and assessed by CLSM. The root canal
      level affected the penetration of the sealer, but no statistical significant
      differences were found between the two experimental groups (p > .05). SP
      presented similar dentinal penetration and perimeter integrity to the gold
      standard (AP). RESEARCH HIGHLIGHTS: Sealer Plus presents dentinal penetrability
      and perimeter integrity similar to the gold standard sealer (AH Plus),
      demonstrating excellent ability of filling areas of difficult access.

PMID- 30295381
TI  - The role of glucagon in the possible mechanism of cardiovascular mortality
      reduction in type 2 diabetes patients.
AB  - AIM: Type 2 diabetes (T2D) is one of the major public health issues worldwide.
      The main cause of mortality and morbidity among T2D patients are cardiovascular
      (CV) causes. Various antidiabetics are used in T2D treatment, but until recently
      they lacked clear evidence of the reduction in CV mortality and all-cause
      mortality as independent study end-points. The aim of this article was to present
      and critically evaluate potential mechanisms behind the remarkable results
      documented in trials with new antidiabetics for the treatment of T2D. METHODS:
      Relevant data were collected using the MEDLINE, PubMed, EMBASE, Web of Science,
      Science Direct, and Scopus databases with the key words: "type 2 diabetes,"
      "mortality," "glucagon," "empagliflozin," "liraglutide," "insulin" and "QTc."
      Searches were not limited to specific publication types or study designs.
      RESULTS: The EMPA-REG OUTCOME trial with empagliflozin and LEADER trial with
      liraglutide presented remarkable results regarding the reduction in mortality in
      T2D treatment. However, the potential mechanism for those beneficial effects is
      difficult to determine. It is not likely that improvements in classic CV risk
      factors are responsible for the observed effect. A potential mechanism may be
      caused by the elevation of postprandial (PP) glucagon concentrations that can be
      seen with an empagliflozin and liraglutide therapy, which could have beneficial
      effects considering the myocardial electrical stability in T2D patients.
      CONCLUSION: This hypothesis throws new light upon possible mechanisms of
      reduction in mortality in T2D patients.

PMID- 30295383
TI  - Sunscreens are no harmless substitutes for mindful behavior under the sun.

PMID- 30295384
TI  - Jessner-Kanof lymphocyte infiltration responded well to impulse intralesional
      corticosteroid.

PMID- 30295385
TI  - Seed surface ultrastructure as an efficient tool for species delimitation in the
      Allium ampeloprasum L. alliance (Amaryllidaceae, Allioideae).
AB  - Seed surface ultrastructure shows a wide variation among different species of the
      genus Allium that could potentially provide valuable characters in inferring the
      relationships. In order to evaluate inter- and intraspecific variation of testa
      microsculpturing in the leek alliance, 33 seed samples of Allium representing its
      two subgenera, six sections, and 23 species were studied. Seed testa surface was
      analyzed using both SEM and Stereomicroscopy. Minor differences in testa cell
      arrangement were observed between members of sect. Allium and sect. Avulsea (both
      of subg. Allium), but major contrasts were discerned between them and members of
      subg. Cepa. Significant similarity was distinguished in anticlinal walls of the
      members of sect. Allium and sect. Avulsea: they were variously undulated (U-, to
      +/-Omega-like). Testa cells in members of subg. Cepa, and some of subg. Allium
      (sect. Caerulea, sect. Codonoprasum, and sect. Longivaginata) showed ribbed
      anticlinal walls suggesting a close relationship between them. The periclinal
      walls were concave, flat to convex with testa cells densely granulose at margins
      in sect. Caerulea; flat to convex, irregularly granulose-verrucose in sect.
      Codonoprasum; concave, densely granulose at margins and center in sect.
      Longivaginata; and convex, densely irregularly granulose, sometimes centrally
      verrucose in subg. Cepa. Irregularly polygonal cells were present in most
      species, but elongated polygonal cells in two species, A. iranicum and A.
      wendelboi (sect. Allium). We found significant micromorphological similarity in
      seed surface features between A. abbasii and A. fuscoviolaceum; A. esfandiarii
      and A. atroviolaceum; and A. longipapillatum and A. rotundum, corroborating close
      relationships.

PMID- 30295386
TI  - The Evaluation of Color and Surface Roughness Changes in Resin based Restorative
      Materials with Different Contents After Waiting in Various Liquids: An SEM and
      AFM study.
AB  - : The aim of the study was to evaluate of surface roughness and color changes of
      the resin-based five restorative dental materials after aging in liquids at
      different pH values. Totally 250 specimens were prepared, including 50 specimens
      for the each material group from five different restorative materials (G1[Filtek
      Z550], G2[Beautifil II], G3[Vertise Flow], G4[Dyract XP], G5[GCFujiIILC]), using
      the 10-mm diameter and 2-mm thickness molds. A total of 50 specimens in the each
      group, were divided into five subgroups (n = 10) to be immerse into five liquids
      at different pH. After initial color and roughness measurements, samples were
      stored in the same liquids for 7 and 14 days and all of the measurements were
      repeated on the 7th and 14th days. scanning electron microscopy and atomic force
      microscopy analyses were performed in the all groups. When the color
      change(DeltaE) results are examined statistically; most of the DeltaE is in Fuji
      II LC; and at least in Filtek Z550, it was determined that cola and gastric acid
      had the greatest effect on DeltaE averages and showed significant differences (p
      < .05). When the average roughness values(Ra) are analyzed statistically, the
      highest values were found in Fuji II LC and the lowest values were found in
      Filtek Z550 (p < .05). The liquids which had the highest roughness average
      (DeltaRa) were statistically significant and gastric acid and orange juice were
      the most effective ones (p < .05). Asidic beverages significantly increased the
      surface roughness and discoloration of dental restorative materials. RESEARCH
      HIGHLIGHTS: The results of this research showed that dental restorative
      materials, which are resin-based, affected both the color and surface roughness
      after waiting in the low pH value beverages. These results are supported with the
      scanning electron microscopy and atomic force microscopy images in our research.
      Clinically, this situation will create esthetic and functional problems in the
      dental filling restorations. For this reason, the results of this study seem to
      be important and we think that this article could be contribute to the
      literature.

PMID- 30295387
TI  - Quantifying the legacy of snowmelt timing on soil greenhouse gas emissions in a
      seasonally dry montane forest.
AB  - The release of water during snowmelt orchestrates a variety of important
      belowground biogeochemical processes in seasonally snow-covered ecosystems,
      including the production and consumption of greenhouse gases (GHGs) by soil
      microorganisms. Snowmelt timing is advancing rapidly in these ecosystems, but
      there is still a need to isolate the effects of earlier snowmelt on soil GHG
      fluxes. For an improved mechanistic understanding of the biogeochemical effects
      of snowmelt timing during the snow-free period, we manipulated a high-elevation
      forest that typically receives over two meters of snowfall but little summer
      precipitation to influence legacy effects of snowmelt timing. We altered snowmelt
      rates for two years using black sand to accelerate snowmelt and white fabric to
      postpone snowmelt, thus creating a two- to three-week disparity in snowmelt
      timing. Soil microclimate and fluxes of carbon dioxide (CO2 ), methane (CH4 ),
      and nitrous oxide (N2 O) were monitored weekly to monthly during the snow-free
      period. Microbial abundances were estimated by potential assays near the end of
      each snow-free period. Although earlier snowmelt caused soil drying, we found no
      statistically significant effects (p < 0.05) of altered snowmelt timing on fluxes
      of CO2 or N2 O, or soil microbial abundances. Soil CH4 fluxes, however, did
      respond to snowmelt timing, with 18% lower rates of CH4 uptake in the earlier
      snowmelt treatment, but only after a dry winter. Cumulative CO2 emission and CH4
      uptake were 43% and 88% greater, respectively, after the dry winter. We conclude
      that soil GHG fluxes can be surprisingly resistant to hydrological changes
      associated with earlier snowmelt, likely because of persistent moisture and
      microbial activities in deeper mineral soils. As a result, a drier California in
      the future may cause seasonally snow-covered soils in the Sierra Nevada to emit
      more GHGs, not less.

PMID- 30295388
TI  - Climate change opens new frontiers for marine species in the Arctic: Current
      trends and future invasion risks.
AB  - Climate change and increased anthropogenic activities are expected to elevate the
      potential of introducing nonindigenous species (NIS) into the Arctic. Yet, the
      knowledge base needed to identify gaps and priorities for NIS research and
      management is limited. Here, we reviewed primary introduction events to each
      ecoregion of the marine Arctic realm to identify temporal and spatial patterns,
      likely source regions of NIS, and the putative introduction pathways. We included
      54 introduction events representing 34 unique NIS. The rate of NIS discovery
      ranged from zero to four species per year between 1960 and 2015. The Iceland
      Shelf had the greatest number of introduction events (n = 14), followed by the
      Barents Sea (n = 11), and the Norwegian Sea (n = 11). Sixteen of the 54
      introduction records had no known origins. The majority of those with known
      source regions were attributed to the Northeast Atlantic and the Northwest
      Pacific, 19 and 14 records, respectively. Some introduction events were
      attributed to multiple possible pathways. For these introductions, vessels
      transferred the greatest number of aquatic NIS (39%) to the Arctic, followed by
      natural spread (30%) and aquaculture activities (25%). Similar trends were found
      for introductions attributed to a single pathway. The phyla Arthropoda and
      Ochrophyta had the highest number of recorded introduction events, with 19 and 12
      records, respectively. Recommendations including vector management, horizon
      scanning, early detection, rapid response, and a pan-Arctic biodiversity
      inventory are considered in this paper. Our study provides a comprehensive record
      of primary introductions of NIS for marine environments in the circumpolar Arctic
      and identifies knowledge gaps and opportunities for NIS research and management.
      Ecosystems worldwide will face dramatic changes in the coming decades due to
      global change. Our findings contribute to the knowledge base needed to address
      two aspects of global change-invasive species and climate change.

PMID- 30295389
TI  - Bleeding events and safety outcomes in persons with haemophilia A with
      inhibitors: A prospective, multi-centre, non-interventional study.
AB  - INTRODUCTION: Prospectively collected, real-world data on bleeds, haemophilic
      treatment and safety outcomes in persons with haemophilia A (PwHA) with factor
      VIII (FVIII) inhibitors are limited. A prospective, global, multi-centre, non
      interventional study (NIS; NCT02476942) collected detailed real-world data in
      PwHA treated per local routine clinical practice. AIM: To characterize bleeding
      rates, haemophilic treatment practices, prophylaxis adherence and adverse events
      (AEs) in adult/adolescent PwHA with inhibitors in the NIS. METHODS: Participants
      aged >=12 years with congenital haemophilia A/documented high-titre FVIII
      inhibitor history were enrolled. Participants remained on their usual treatment;
      no interventions were applied. RESULTS: Overall, 103 PwHA with inhibitors
      enrolled, (median [range] age 31 [12-75] years) and were monitored for median
      (range) 26.0 (4.1-69.6) weeks. In the episodic (n = 75) and prophylactic (n = 28)
      treatment groups, respectively, 1244 and 325 bleeds were reported, and 528
      (42.4%) and 104 (32.0%) were not treated; annualized bleeding rates (ABRs; 95%
      confidence interval) were 18.6 (15.2-22.8) and 14.9 (10.5-21.2) for treated
      bleeds, and 32.7 (27.3-39.1) and 25.0 (18.4-34.0) for all bleeds. Coagulation
      products used included activated prothrombin complex concentrate (aPCC) and/or
      recombinant activated FVII. Among participants prescribed aPCC prophylaxis, 35.0%
      adhered to both prescribed frequency of aPCC administration and prescribed dose.
      Serious AEs of haemarthrosis and muscle haemorrhage were reported; most common
      AEs were arthralgia, viral upper respiratory tract infection and pyrexia.
      CONCLUSIONS: ABRs (treated bleeds and all bleeds) remain high on standard
      treatment; this prospective NIS demonstrates the need for more effective
      treatments for PwHA with inhibitors to reduce/prevent bleeds, with potential to
      improve prophylaxis adherence and further improve outcomes.

PMID- 30295390
TI  - Ocean acidification increases iodine accumulation in kelp-based coastal food
      webs.
AB  - Kelp are main iodine accumulators in the ocean, and their growth and
      photosynthesis are likely to benefit from elevated seawater CO2 levels due to
      ocean acidification. However, there are currently no data on the effects of ocean
      acidification on iodine metabolism in kelp. As key primary producers in coastal
      ecosystems worldwide, any change in their iodine metabolism caused by climate
      change will potentially have important consequences for global geochemical cycles
      of iodine, including iodine levels of coastal food webs that underpin the
      nutrition of billions of humans around the world. Here, we found that elevated
      pCO2 enhanced growth and increased iodine accumulation not only in the model kelp
      Saccharina japonica using both short-term laboratory experiment and long-term in
      situ mesocosms, but also in several other edible and ecologically significant
      seaweeds using long-term in situ mesocosms. Transcriptomic and proteomic analysis
      of S. japonica revealed that most vanadium-dependent haloperoxidase genes
      involved in iodine efflux during oxidative stress are down-regulated under
      increasing pCO2 , suggesting that ocean acidification alleviates oxidative stress
      in kelp, which might contribute to their enhanced growth. When consumed by
      abalone (Haliotis discus), elevated iodine concentrations in S. japonica caused
      increased iodine accumulation in abalone, accompanied by reduced synthesis of
      thyroid hormones. Thus, our results suggest that kelp will benefit from ocean
      acidification by a reduction in environmental stress however, iodine levels in
      kelp-based coastal food webs will increase, with potential impacts on
      biogeochemical cycles of iodine in coastal ecosystems. This article is protected
      by copyright. All rights reserved.

PMID- 30295391
TI  - Circadian disruption favors alcohol consumption and differential DeltaFosB
      accumulation in Corticolimbic structures.
AB  - Shift-work and exposure to light at night lead to circadian disruption, which
      favors the use of alcohol and may be a risk factor for development of addictive
      behavior. This study evaluated in two experimental models of circadian disruption
      behavioral indicators of elevated alcohol intake and looked for DeltaFosB, which
      is a transcription factor for neuronal plasticity in corticolimbic structures.
      Male Wistar rats were exposed to experimental shift-work (AR) or to constant
      light (LL) and were compared with a control group (LD). After 4 weeks in their
      corresponding conditions, control LD rats remained rhythmic, AR rats exhibited a
      loss of day-night patterns in the brain and the LL rats showed arrhythmicity in
      general activity and day-night PER1 patterns in corticolimbic structures. During
      12 days of exposure to 10 percent alcohol solution, the AR group showed daily
      increased alcohol intake while LD and LL rats ingested similar amounts. After 72
      h of alcohol deprivation, AR and LL rats increased alcohol intake in a binge-like
      test; this could be due not only to circadian disruption but also to stress
      and/or anxiety developed from the AR and LL manipulations. Associated to the
      increased alcohol intake, the AR and LL rats had significant accumulation of
      DeltaFosB in the nucleus accumbens shell and decreased DeltaFosB in the
      infralimbic cortex. Data here reported confirm that the disruption of temporal
      patterns favors the increased alcohol consumption and that this is associated
      with a differential accumulation of DeltaFosB which may favor the development of
      addictive behavior.

PMID- 30295392
TI  - Survey to estimate the prevalence of type 2 diabetes mellitus in hospital
      patients in Germany by systematic HbA1c measurement upon admission.
AB  - OBJECTIVES: The objective of this survey was to estimate the prevalence of type 2
      diabetes mellitus (T2DM) in hospitalised patients >=55 years based on routine
      HbA1c measurement upon admission, using the diagnosis algorithm according to the
      German National Diabetes Care Guideline. DESIGN: Non-interventional survey.
      SETTING: Four German maximum care hospitals. POPULATION: Consecutive patients
      >=55 years of age admitted to hospital. MAIN OUTCOME MEASURES: Participating
      hospitals measured HbA1c upon admission and applied the algorithm for diagnosing
      T2DM per the clinical recommendations of the American Diabetes Association (ADA)
      and the German National Diabetes Care Guideline as part of the clinical routine
      and allocated patients to three diagnostic categories: T2DM, increased risk for
      T2DM, no T2DM. RESULTS: Between Oct 2014 and May 2015, the survey documented data
      from 6092 patients; the analyses included 5820 patients fulfilling validity
      criteria (95.5%). Of these, 1906 (32.7%) had a known history of T2DM. Among the
      3914 remaining patients, 2181 had no T2DM (55.8%), 1180 an increased risk for
      T2DM (30.1%) and 553 unrecognised T2DM (14.1%; 95% CI: 13.1%-15.3%). The overall
      prevalence of known and unrecognised T2DM was 42.3% (95% CI: 41.0%-43.5%).
      Patients with previously unrecognised T2DM were admitted to hospital
      predominantly for cardiac disorders (21.9%), nervous system disorders such as
      cerebral infarction (15.0%) and infections/infestations (13.4%). CONCLUSIONS:
      This survey revealed an overall prevalence of known and unrecognised T2DM of more
      than 40%. Among patients with unrecognised T2DM on admission, the prevalence of
      T2DM was 14%. These data indicate that systematic documentation of T2DM in in
      patients is clinically useful. Hospitals should consider using the diagnostic
      algorithm and to streamline pathways of care to secure adequate care considering
      patients' diabetic risk profiles, and to manage related additional costs.

PMID- 30295394
TI  - Contribution of soil inorganic carbon to atmospheric CO2 : More important than
      previously thought.

PMID- 30295393
TI  - The greenhouse gas cost of agricultural intensification with groundwater
      irrigation in a Midwest U.S. row cropping system.
AB  - Groundwater irrigation of cropland is expanding worldwide with poorly known
      implications for climate change. This study compares experimental measurements of
      the net global warming impact of a rainfed versus a groundwater-irrigated corn
      (maize)-soybean-wheat, no-till cropping system in the Midwest US, the region that
      produces the majority of U.S. corn and soybean. Irrigation significantly
      increased soil organic carbon (C) storage in the upper 25 cm, but not by enough
      to make up for the CO2 -equivalent (CO2 e) costs of fossil fuel power, soil
      emissions of nitrous oxide (N2 O), and degassing of supersaturated CO2 and N2 O
      from the groundwater. A rainfed reference system had a net mitigating effect of 
      13.9 (+/-31) g CO2 e m-2  year-1 , but with irrigation at an average rate for the
      region, the irrigated system contributed to global warming with net greenhouse
      gas (GHG) emissions of 27.1 (+/-32) g CO2 e m-2  year-1 . Compared to the rainfed
      system, the irrigated system had 45% more GHG emissions and 7% more C
      sequestration. The irrigation-associated increase in soil N2 O and fossil fuel
      emissions contributed 18% and 9%, respectively, to the system's total emissions
      in an average irrigation year. Groundwater degassing of CO2 and N2 O are missing
      components of previous assessments of the GHG cost of groundwater irrigation;
      together they were 4% of the irrigated system's total emissions. The irrigated
      system's net impact normalized by crop yield (GHG intensity) was +0.04 (+/-0.006)
      kg CO2 e kg-1 yield, close to that of the rainfed system, which was -0.03 (+/
      0.002) kg CO2 e kg-1 yield. Thus, the increased crop yield resulting from
      irrigation can ameliorate overall GHG emissions if intensification by irrigation
      prevents land conversion emissions elsewhere, although the expansion of
      irrigation risks depletion of local water resources.

PMID- 30295395
TI  - Characterization of follicular minoxidil sulfotransferase activity in a cohort of
      pattern hair loss patients from the Indian Subcontinent.
AB  - Several studies have established that sulfotransferase enzyme activity in the
      outer root sheath of plucked hair follicles predicts response to topical
      minoxidil in the treatment of pattern hair loss. However, the prevalence of this
      enzyme activity among Indian patients has not been studied. Additionally, no
      reports in the literature characterize sulfotransferase activity based on sex,
      age, duration of hair loss, grade of hair loss, and family history. In this study
      we utilized a sulfotransferase activity assay first reported by Goren et al. We
      characterize the follicular sulfotransferase activity of 120 pattern hair loss
      patients visiting a dermatology outpatient clinic in India. Overall, 40.8% of
      patients with pattern hair loss had low levels of sulfotransferase. Surprisingly,
      49.3% of men had low levels of sulfotransferase compared to 26.6% of women. No
      correlation was found between sulfotransferase activity and age, duration of hair
      loss, grade of hair loss, or family history. A sub-analysis of patient reported
      outcomes (PRO) validated previous findings that sulfotransferase enzyme activity
      is a predictive marker for minoxidil response in pattern hair loss patients.

PMID- 30295396
TI  - Hypothalamic response to cocaine cues and cocaine addiction severity.
AB  - The dopaminergic motive system is compromised in cocaine addiction. Abundant
      research has examined the roles of the dopaminergic midbrain and ventral striatum
      (VS) in cue-induced craving and habitual drug consumption. Interconnected with
      the dopaminergic circuits, the hypothalamus is widely implicated in motivated
      behavior, including food and drug seeking. However, very few studies have
      investigated how the hypothalamus responds to drug cues and whether hypothalamic
      responses are related to clinical features such as craving and addiction
      severity. Here, in 23 cocaine-dependent individuals (CD) exposed to cocaine vs
      neutral cues during functional magnetic resonance imaging (fMRI), we examined
      regional responses using established routines. At a corrected threshold, CD
      demonstrated increased activation to cocaine vs neutral cues in bilateral visual
      cortex, inferior parietal and middle frontal gyri, and the hypothalamus. The
      extent of hypothalamus but not other regional response was correlated with
      craving and cocaine addiction severity, each as assessed by the Cocaine Craving
      Questionnaire (CCQ) and Cocaine Selective Severity Assessment (CSSA). In
      contrast, subjective "acute" craving as elicited by cocaine cues during fMRI
      involved deactivation of bilateral orbitofrontal cortex (OFC) and angular gyri
      (AG), and the OFC and AG responses were not related to CCQ or CSSA score. These
      findings distinguished tonic craving as a critical factor in capturing cocaine
      addiction severity and substantiated a role of the hypothalamus in motivational
      dysfunction in cocaine addiction.

PMID- 30295397
TI  - The response of boreal peatland community composition and NDVI to hydrologic
      change, warming, and elevated carbon dioxide.
AB  - Widespread changes in arctic and boreal Normalized Difference Vegetation Index
      (NDVI) values captured by satellite platforms indicate that northern ecosystems
      are experiencing rapid ecological change in response to climate warming.
      Increasing temperatures and altered hydrology are driving shifts in ecosystem
      biophysical properties that, observed by satellites, manifest as long-term
      changes in regional NDVI. In an effort to examine the underlying ecological
      drivers of these changes, we used field-scale remote sensing of NDVI to track
      peatland vegetation in experiments that manipulated hydrology, temperature, and
      carbon dioxide (CO2 ) levels. In addition to NDVI, we measured percent cover by
      species and leaf area index (LAI). We monitored two peatland types broadly
      representative of the boreal region. One site was a rich fen located near
      Fairbanks, Alaska, at the Alaska Peatland Experiment (APEX), and the second site
      was a nutrient-poor bog located in Northern Minnesota within the Spruce and
      Peatland Responses Under Changing Environments (SPRUCE) experiment. We found that
      NDVI decreased with long-term reductions in soil moisture at the APEX site,
      coincident with a decrease in photosynthetic leaf area and the relative abundance
      of sedges. We observed increasing NDVI with elevated temperature at the SPRUCE
      site, associated with an increase in the relative abundance of shrubs and a
      decrease in forb cover. Warming treatments at the SPRUCE site also led to
      increases in the LAI of the shrub layer. We found no strong effects of elevated
      CO2 on community composition. Our findings support recent studies suggesting that
      changes in NDVI observed from satellite platforms may be the result of changes in
      community composition and ecosystem structure in response to climate warming.

PMID- 30295398
TI  - Delayed herbivory by migratory geese increases summer-long CO2 uptake in coastal
      western Alaska.
AB  - The advancement of spring and the differential ability of organisms to respond to
      changes in plant phenology may lead to "phenological mismatches" as a result of
      climate change. One potential for considerable mismatch is between migratory
      birds and food availability in northern breeding ranges, and these mismatches may
      have consequences for ecosystem function. We conducted a three-year experiment to
      examine the consequences for CO2 exchange of advanced spring green-up and altered
      timing of grazing by migratory Pacific black brant in a coastal wetland in
      western Alaska. Experimental treatments represent the variation in green-up and
      timing of peak grazing intensity that currently exists in the system. Delayed
      grazing resulted in greater net ecosystem exchange (NEE) and gross primary
      productivity (GPP), while early grazing reduced CO2 uptake with the potential of
      causing net ecosystem carbon (C) loss in late spring and early summer.
      Conversely, advancing the growing season only influenced ecosystem respiration
      (ER), resulting in a small increase in ER with no concomitant impact on GPP or
      NEE. The experimental treatment that represents the most likely future, with
      green-up advancing more rapidly than arrival of migratory geese, results in NEE
      changing by 1.2 umol m-2  s-1 toward a greater CO2 sink in spring and summer.
      Increased sink strength, however, may be mitigated by early arrival of migratory
      geese, which would reduce CO2 uptake. Importantly, while the direct effect of
      climate warming on phenology of green-up has a minimal influence on NEE, the
      indirect effect of climate warming manifest through changes in the timing of peak
      grazing can have a significant impact on C balance in northern coastal wetlands.
      Furthermore, processes influencing the timing of goose migration in the winter
      range can significantly influence ecosystem function in summer habitats.

PMID- 30295399
TI  - Natural history of a cohort of ABCD1 variant female carriers.
AB  - BACKGROUND AND PURPOSE: The therapeutic scenario of X-linked adrenoleukodystrophy
      (X-ALD) is rapidly changing. Whereas the disease is well characterized in men,
      the condition remains to be fully clarified in women carrying ATP binding
      cassette subfamily D member 1 (ABCD1) variants. Specifically, data on clinical
      progression are needed, in order to recommend any appropriate management. The
      objective of this study was to outline the natural history of a cohort of
      untreated ABCD1 heterozygous female carriers. METHODS: Longitudinal data from a
      single-center population of 60 carriers were retrospectively reviewed.
      Demographics, anthropometrics, serum very long chain fatty acid (VLCFA) levels,
      clinical parameters and the Adult ALD Clinical Score (AACS) were collected from
      every recorded visit in a 7-year period and analyzed to define the phenotype
      modifications, to determine factors associated with clinical features, and to
      estimate the annual progression rate and the subsequent sample size for
      interventional trials. RESULTS: Thirty-two patients were eligible for the study,
      and 59.4% were symptomatic at baseline. Clinical severity worsens with age which
      increases risk of symptom onset, the cut-off of 41 years being crucial for
      phenoconversion. VLCFA levels were not predictive and did not change over time.
      Symptomatic carriers were followed up for 3.45 +/- 2.1 years. The AACS increased
      at an annual rate of 0.24 points. The estimated sample size for 30% reduction in
      annual progression at 80% power was 272. CONCLUSIONS: This study provides data on
      the natural disease progression of untreated ABCD1 heterozygous female carriers,
      demonstrating the relevance of aging. The estimated annual increase of the AACS
      will be useful for future interventional studies.

PMID- 30295400
TI  - Preliminary evidence of different and clinically meaningful opioid withdrawal
      phenotypes.
AB  - Opioid use disorder (OUD) is a public health crisis. Differences in opioid
      withdrawal severity that predict treatment outcome could facilitate the process
      of matching patients to treatments. This is a secondary analysis of a randomized
      controlled trial (RCT) that enrolled treatment seeking heroin-users (N = 89,
      males = 78) into a residential study. Participants maintained on morphine (30 mg,
      subcutaneous, four-times daily) underwent a naloxone (0.4 mg, IM = intramuscular)
      challenge session to precipitate withdrawal. Area-under-the-curve (AUC) values
      from self-reported withdrawal ratings during the challenge session were analyzed
      using K-means clustering, revealing two phenotype groups. Withdrawal and
      retention from the subsequent 14-day double-blind, double-dummy RCT comparing
      three study medications (clonidine, tramadol-ER, and buprenorphine) were
      evaluated as a function of phenotype. Cluster analyses suggested HIGH (N = 37;
      mean [SD] subjective opiate withdrawal scale [SOWS]-AUC 123.7 [65.8]) and LOW (N
      = 52; SOWS-AUC 68.0 [47.7]) withdrawal phenotype groups. HIGH participants were
      significantly more female and had lower body mass indices than LOW participants;
      no drug-use variables were significant. Regarding RCT outcomes, HIGH phenotype
      participants were less likely to be retained in the study (P = 0.02) and had
      higher mean self-reported withdrawal (P = 0.05) than LOW phenotype participants.
      A significant interaction in RCT retention was observed between phenotype (P =
      0.02) and study medication (P < 0.01). Self-reported withdrawal was significant
      for phenotype (P = 0.02); study medication trended towards significance (P =
      0.07). Results suggest patients have meaningfully different experiences of opioid
      withdrawal that may predict differential response to opioid pharmacotherapies
      during supervised withdrawal. Additional prospective research to replicate and
      more thoroughly evaluate withdrawal phenotype correlates and sex differences is
      warranted.

PMID- 30295401
TI  - Consistent trophic amplification of marine biomass declines under climate change.
AB  - The impact of climate change on the marine food web is highly uncertain.
      Nonetheless, there is growing consensus that global marine primary production
      will decline in response to future climate change, largely due to increased
      stratification reducing the supply of nutrients to the upper ocean. Evidence to
      date suggests a potential amplification of this response throughout the trophic
      food web, with more dramatic responses at higher trophic levels. Here we show
      that trophic amplification of marine biomass declines is a consistent feature of
      the Coupled Model Intercomparison Project Phase 5 (CMIP5) Earth System Models,
      across different scenarios of future climate change. Under the business-as-usual
      Representative Concentration Pathway 8.5 (RCP8.5) global mean phytoplankton
      biomass is projected to decline by 6.1% +/- 2.5% over the twenty-first century,
      while zooplankton biomass declines by 13.6% +/- 3.0%. All models project greater
      relative declines in zooplankton than phytoplankton, with annual zooplankton
      biomass anomalies 2.24 +/- 1.03 times those of phytoplankton. The low latitude
      oceans drive the projected trophic amplification of biomass declines, with models
      exhibiting variable trophic interactions in the mid-to-high latitudes and similar
      relative changes in phytoplankton and zooplankton biomass. Under the assumption
      that zooplankton biomass is prey limited, an analytical explanation of the
      trophic amplification that occurs in the low latitudes can be derived from
      generic plankton differential equations. Using an ocean biogeochemical model, we
      show that the inclusion of variable C:N:P phytoplankton stoichiometry can
      substantially increase the trophic amplification of biomass declines in low
      latitude regions. This additional trophic amplification is driven by enhanced
      nutrient limitation decreasing phytoplankton N and P content relative to C, hence
      reducing zooplankton growth efficiency. Given that most current Earth System
      Models assume that phytoplankton C:N:P stoichiometry is constant, such models are
      likely to underestimate the extent of negative trophic amplification under
      projected climate change.

PMID- 30295402
TI  - Uneven winter snow influence on tree growth across temperate China.
AB  - Winter snow is an important driver of tree growth in regions where growing-season
      precipitation is limited. However, observational evidence of this influence at
      larger spatial scales and across diverse bioclimatic regions is lacking. Here, we
      investigated the interannual effects of winter (here defined as previous October
      to current February) snow depth on tree growth across temperate China over the
      period of 1961-2015, using a regional network of tree ring records, in situ daily
      snow depth observations, and gridded climate data. We report uneven effects of
      winter snow depth on subsequent growing-season tree growth across temperate
      China. There shows little effect on tree growth in drier regions that we
      attribute mainly to limited snow accumulation during winter. By contrast, winter
      snow exerts important positive influence on tree growth in stands with high
      winter snow accumulation (e.g., in parts of cold arid regions). The magnitude of
      this effect depends on the proportion of winter snow to pre-growing-season
      (previous October to current April) precipitation. We further observed that tree
      growth in drier regions tends to be increasingly limited by warmer growing-season
      temperature and early growing-season water availability. No compensatory effect
      of winter snow on the intensifying drought limitation of tree growth was observed
      across temperate China. Our findings point toward an increase in drought
      vulnerability of temperate forests in a warming climate.

PMID- 30295403
TI  - Diversity-Oriented Construction and Interconversion of Multicavity
      Supermacrocycles for Cooperative Anion-pi Binding.
AB  - A one-pot strategy for the diverse construction of a series of supermacrocycles
      was realized using rationally designed macrocyclic precursors. The base was found
      to have a significant effect not only on the size distribution but also on the
      structure of the supermacrocycles formed. While the use of less CsF (<4.0 equiv)
      afforded regular supermacrocycles containing up to four macrocyclic precursor
      subunits, the use of more CsF (>8.0 equiv) resulted in structurally reorganized
      supermacrocyles featuring oxacalix[2]arene[2]triazine motifs. Base-mediated
      supermacrocycle-to-supermacrocycle transformations were also revealed. With large
      cavities and many electron-deficient triazine moieties, the supermacrocyles can
      accommodate large organic anions via multiple anion-pi interactions as
      demonstrated for two supermacrocycles, which can host 2-carboxyacetate and
      represent the first crystallographic examples of sandwich-like structures with
      anion-pi interactions.

PMID- 30295404
TI  - Investigating the relationship between the HJHS and HAL in routine clinical
      practice: A retrospective review.
AB  - INTRODUCTION: Comprehensive musculoskeletal assessment for monitoring joint
      health in haemophilia includes both physical assessment with Haemophilia Joint
      Health Score (HJHS) and assessment of self-reported function by Haemophilia
      Activities List (HAL). METHODS: Correlation between physical assessment and joint
      function was undertaken between HJHS and HAL in patients with SHA and SHB who had
      both assessments at the same visit over a one-year period. RESULTS: Data from 120
      patients (96-SHA/24 = SHB) with a median age 33 years (range 19-73) were
      included. Median total HJHS was 19, increasing with age: 18-30 years-7, 31-50
      years-25 and 51-73 years-44. Similarly, median total HAL score was 80 with
      decreased function associated with increasing age: 18-30 years-90.4, 31-59 years
      71.7, 51-73 years-49.5. Median Total HJHS and HAL demonstrated strong correlation
      (rs  = 0.66, P < 0.01). Moderate-to-strong correlations were seen across the
      entire age group between the HJHS LL and UL subtotals and corresponding limb HAL
      domains. Within age groups, correlations were less significant particularly for
      the upper UL domains in HAL and the UL HJHS score. The wide range of ROM in
      joints categorized as markedly affected (ie, ROM loss score = 3) highlights the
      potential ceiling effect of this domain score and its use in chronically damaged
      joints. CONCLUSION: HJHS and HAL showed moderate-to-strong correlation with
      discrepancy in some individual patients. Prospective studies are required to
      better understand the clinical utility of both especially in severe joint disease
      where HAL may have a potential advantage.

PMID- 30295405
TI  - Trade-offs between soil carbon sequestration and reactive nitrogen losses under
      straw return in global agroecosystems.
AB  - It is widely recommended that crop straw be returned to croplands to maintain or
      increase soil carbon (C) storage in arable soils. However, because C and nitrogen
      (N) biogeochemical cycles are closely coupled, straw return may also affect soil
      reactive N (Nr) losses, but these effects remain uncertain, especially in terms
      of the interactions between soil C sequestration and Nr losses under straw
      addition. Here, we conducted a global meta-analysis using 363 publications to
      assess the overall effects of straw return on soil Nr losses, C sequestration and
      crop productivity in agroecosystems. Our results show that on average, compared
      to mineral N fertilization, straw return with same amount of mineral N fertilizer
      significantly increased soil organic C (SOC) content (14.9%), crop yield (5.1%),
      and crop N uptake (10.9%). Moreover, Nr losses in the form of nitrous oxide (N2
      O) emissions from rice paddies (17.3%), N leaching (8.7%), and runoff (25.6%)
      were significantly reduced, mainly due to enhanced microbial N immobilization.
      However, N2 O emissions from upland fields (21.5%) and ammonia (NH3 ) emissions
      (17.0%) significantly increased following straw return, mainly due to the
      stimulation of nitrification/denitrification and soil urease activity. The
      increase in NH3 and N2 O emissions was significantly and negatively correlated
      with straw C/N ratio and soil clay content. Regarding the interactions between C
      sequestration and Nr losses, the increase in SOC content following straw return
      was significantly and positively correlated with the decrease in N leaching and
      runoff. However, at a global scale, straw return increased net Nr losses from
      both rice and upland fields due to a greater stimulation of NH3 emissions than
      the reduction in N leaching and runoff. The trade-offs between increased net Nr
      losses and soil C sequestration highlight the importance of reasonably managing
      straw return to soils to limit NH3 emissions without decreasing associated C
      sequestration potential.

PMID- 30295406
TI  - Donor-derived strongyloidiasis after organ transplantation in Norway.
AB  - Strongyloides stercoralis is an intestinal helminth which in humans can cause
      asymptomatic chronic infection maintained for decades through its auto-infective
      cycle. During solid organ transplantation, recipients may unintentionally receive
      an organ infected with strongyloides. This is a very rare complication but may
      have deadly outcome if not detected. We hereby report two transplant recipients
      whom developed Strongyloides hyperinfection syndrome after organ transplantation
      from the same deceased donor. Recipient 1 was kidney transplanted and presented
      at day 65 post engraftment with diarrhea and subsequent septicemia and gastric
      retention. Larvae were detected in gastric aspirate. Recipient 2 was
      simultaneously kidney and pancreas transplanted and presented at day 90 post
      engraftment also with gastric retention and septicemia. Larvae were demonstrated
      on duodenal biopsy and stool sample. The clinical course was complicated with
      severe duodenal bleedings, gastric retention, meningitis, and prolonged
      hospitalization. Retrospective testing of pre-transplant donor serum was positive
      for Strongyloides stercoralis antibodies. As a result of disease severity and
      gastric retention albenazole was administered via a jejunal tube and ivermectin
      subcutaneously in both recipients. S stercoralis was successfully eradicated and
      the transplants ended up with unaffected graft function. Following these two
      cases, we started systematic screening of all deceased donors for serum
      Strongyloides IgG in October 2016. After having screened 150 utilized donors one
      tested positive for Strongyloides, which initiated prophylactic ivermectin
      treatment to organ recipients. No symptoms or disease developed. Our center will
      continue to screen all donors as prophylactic treatment may avert this
      potentially lethal complication in cases of donor-derived Strongyloides
      infection.

PMID- 30295407
TI  - Effect of isavuconazole on tacrolimus and sirolimus serum concentrations in
      allogeneic hematopoietic stem cell transplant patients: A drug-drug interaction
      study.
AB  - INTRODUCTION: Isavuconazole, a triazole antifungal, is an inhibitor of cytochrome
      P450 3A4, which also metabolizes tacrolimus and sirolimus. In previous studies,
      isavuconazole administration increased tacrolimus and sirolimus area under the
      curve values by 2.3-fold and 1.8-fold, respectively, in healthy adults and
      tacrolimus concentration/dose (C/D) ratio by 1.3-fold in solid organ transplant
      patients. We aimed to determine the magnitude of effect of isavuconazole
      administration on tacrolimus and sirolimus C/D ratios in allogeneic hematopoietic
      stem cell transplant (alloHSCT) patients. METHODS: A retrospective, single
      center, single-arm study in adult alloHSCT patients who received at least 10 days
      of combination therapy with isavuconazole and tacrolimus and/or sirolimus as
      inpatients or outpatients was conducted. Tacrolimus and sirolimus trough serum
      concentrations were measured up to twice weekly for up to 4 weeks. RESULTS:
      Twenty-two patients receiving tacrolimus and twenty patients receiving sirolimus
      met the inclusion criteria. The mean C/D ratio increased from baseline by 1.42
      fold for tacrolimus during week 1 (P = 0.002) and up to 1.56-fold for sirolimus
      during week 2 (P = 0.02). For the remaining timepoints, tacrolimus and sirolimus
      C/D ratios were not statistically significantly different from baseline.
      CONCLUSION: In alloHSCT patients, modest increases in tacrolimus and sirolimus
      C/D ratios from baseline were observed within the first 2 weeks after initiation
      of isavuconazole.

PMID- 30295408
TI  - Effect of adjuvant radiotherapy on the local recurrence of oral squamous cell
      carcinoma with perineural invasion: A systematic review.
AB  - OBJECTIVES OF THE REVIEW: The decision whether to include postoperative
      radiotherapy on patients with oral squamous cell carcinoma depends on the risk of
      local recurrence. The objectives of this study were to systematically review
      literature on whether perineural invasion in oral squamous cell carcinoma
      patients is associated with higher local recurrence rates and whether local
      recurrence is influenced by the administration of postoperative radiotherapy in
      patients presenting with perineural invasion. TYPE OF REVIEW: Systematic review.
      SEARCH STRATEGY: Embase, PubMed, Web Of Science. EVALUATION METHOD: The databases
      above were searched for studies that analysed: the treatment of oral squamous
      cell carcinoma patients with perineural invasion, local recurrence and
      postoperative radiotherapy. The data of seven studies were analysed
      qualitatively. RESULTS: The overall quality of the studies was moderate to low.
      There was no evidence of the effect of postoperative radiotherapy on local
      recurrence rates in patients presenting with perineural invasion. Some evidence
      suggests that local recurrence rates may increase in cases of multifocal
      perineural invasion, especially if nerves >1 mm are involved but these data
      should be interpreted with caution due to the low-quality evidence. CONCLUSIONS:
      High-quality evidence regarding the prognostic value of perineural invasion and
      the impact of postoperative radiotherapy in patients presenting with perineural
      invasion is lacking in the literature, making it difficult to select a
      postoperative strategy for early-stage tumours.

PMID- 30295409
TI  - Withdrawal from long-term use of zopiclone, zolpidem and temazepam may improve
      perceived sleep and quality of life in older adults with primary insomnia.
AB  - Long-term use of benzodiazepines or benzodiazepine receptor agonists is
      widespread, although guidelines recommend short-term use. Only few controlled
      studies have characterized the effect of discontinuation of their chronic use on
      sleep and quality of life. We studied perceived sleep and quality of life in 92
      older (age 55-91 years) outpatients with primary insomnia before and after
      withdrawal from long-term use of zopiclone, zolpidem or temazepam (BZDA). BZDA
      was withdrawn during 1 month, during which the participants received psychosocial
      support and blindly melatonin or placebo. A questionnaire was used to study
      perceived sleep and quality of life before withdrawal, and 1 month and 6 months
      later. 89 participants completed the 6-month follow-up. As melatonin did not
      improve withdrawal, all participants were pooled and then separated based solely
      on the withdrawal results at 6 months (34 Withdrawers. 55 Nonwithdrawers) for
      this secondary analysis. At 6 months, the Withdrawers had significantly (P <
      0.05) shorter sleep-onset latency and less difficulty in initiating sleep than at
      baseline and when compared to Nonwithdrawers. Compared to baseline, both
      Withdrawers and Nonwithdrawers had at 6 months significantly (P < 0.05) less
      fatigue during the morning and daytime. Stress was alleviated more in Withdrawers
      than in Nonwithdrawers (P < 0.05). Satisfaction with life and expected health 1
      year later improved (P < 0.05) in Withdrawers. In conclusion, sleep disturbances,
      daytime fatigue and impaired quality of life may resolve within 6 months of BZDA
      withdrawal. These results encourage withdrawal from chronic use of benzodiazepine
      type hypnotics, particularly in older subjects.

PMID- 30295410
TI  - Randomized and controlled study comparing patient controlled and radiologist
      controlled intra-procedural conscious sedation, using midazolam and fentanyl, for
      patients undergoing insertion of a central venous line.
AB  - INTRODUCTION: Interventional Radiology procedures can provoke anxiety and may be
      painful. Current practice, Radiologist Controlled Sedation (RCS), involves
      titrating aliquots of midazolam and fentanyl to patient response but underdosing
      and overdosing may occur. This study tests a new method of titrating
      sedation/analgesia during the procedure, Patient Controlled Sedation (PCS), in
      which a combination of fentanyl and midazolam are administered using a patient
      controlled analgesia pump. This allows the patient to self-control their
      sedation/analgesia during the procedure. METHODS: We performed a randomised
      control trial comparing the effects of pain, sedation, amnesia and overall
      patient satisfaction between PCS and RCS, by enrolling forty patients undergoing
      insertion of a tunnelled central line. RESULTS: Our results showed that PCS was
      safe, with no adverse events. PCS was effective in providing sedation, amnesia
      and overall pain relief comparable to RCS. There was no significant difference in
      dose given to patients using PCS or RCS. There was a tendency for patients in the
      PCS group to begin sedation later than those in the RCS group, but both were
      equally sedated during the procedure. We show that patients in the PCS group were
      very satisfied with the procedure. CONCLUSIONS: We show that PCS is non-inferior
      to RCS in terms of dosage given and degree of sedation. To the authors'
      knowledge, this is the first study to show intra-procedural PCS in an
      Interventional Radiology setting using midazolam and fentanyl as a randomised
      comparative trial. It has wide applicability in a procedural setting for very low
      cost and with minimal additional training required.

PMID- 30295411
TI  - Androgen deprivation therapy use with post-prostatectomy radiotherapy in the
      Prostate Cancer Outcomes Registry Victoria.
AB  - INTRODUCTION: The aim of this study is to evaluate the use of androgen
      deprivation therapy (ADT) with post-prostatectomy radiotherapy (PPRT) in a
      population-based cohort of Australian men. METHODS: This is a prospective cohort
      of men with localised prostate cancer captured in the Prostate Cancer Outcomes
      Registry Victoria (PCOR-Vic), who received PPRT between January 2010 and December
      2015. The primary outcome was ADT use with PPRT. Multivariate logistic
      regressions were used to identify patient, tumour and institutional factors
      influencing ADT use. RESULTS: 485 men were included in this study - 115 (24%) had
      pT2 disease, 231 (48%) pT3a, 134 (28%) pT3b and 5 (1%) pT4. Eighteen (4%) men had
      ISUP grade 1 disease, 139 (29%) ISUP grade 2, 170 (35%) ISUP grade 3 and 158
      (33%) ISUP grade 4/5, while 267 (64%) men had positive surgical margins. Median
      time from prostatectomy to PPRT was 8.1 months (IQR = 5.3-13.9). Sixty-six (14%)
      patients had ADT with PPRT. In multivariate analyses, men who had increased age
      (OR = 1.06; 95% CI = 1.01-1.11), seminal vesicle involvement (OR = 3.81; 95% CI =
      1.63-8.91) and underwent treatment in regional centres (OR = 2.17; 95% CI = 1.08
      4.33) were more likely to have ADT with PPRT. CONCLUSION: We reported that 14% of
      men treated with PPRT received ADT in a population-based cohort of Australian
      men, which was less than half of the proportion of ADT use with PPRT in the US.
      It will be of interest to evaluate the uptake of ADT with PPRT in the coming
      years following recent publications of level 1 evidence confirming overall
      survival benefits of ADT with PPRT.

PMID- 30295412
TI  - Risk of hepatitis B reactivation in hepatitis B surface antigen seronegative and
      core antibody seropositive kidney transplant recipients.
AB  - BACKGROUND: Previous contact with Hepatitis B virus (HBV) is common in patients
      undergoing hemodialysis. Literature has shown conflicting results on the risk of
      HBV reactivation in kidney transplant (KT) recipients with serologic evidence of
      past HBV infection. METHODS: We reviewed 631 consecutive KT recipients and
      selected 70 patients simultaneously HBsAg negative and anti-HBc positive before
      KT, regardless of hepatitis B surface antibody (anti-HBs) status. Demographic
      characteristics, coinfection with other viruses, the presence of a previous KT,
      induction and maintenance immunosuppression, length of follow up, biopsy-proven
      acute rejection episodes, incidence of impaired liver function, and causes of
      graft loss and mortality were collected. Hepatitis B virus reactivation was
      defined as detection of HBV DNA viral load >2000 IU/mL during follow up. Outcome
      data included HBV reactivation episodes, graft function, and patient survival.
      RESULTS: Median follow-up was 151 months; 91.4% of patients were positive to anti
      HBs prior to KT. No patient received HBV prophylaxis and 11 patients (15.7%)
      received rituximab as part of induction therapy. Anti-HBs titers remained stable
      in all patients throughout the observation period but two patient showed evidence
      of HBV reactivation after KT. CONCLUSION: Hepatitis B virus reactivation in HBsAg
      negative and anti-HBc-positive after KT is rare but possible. We suggest
      evaluating HBV serologies, HBV DNA viral load, and liver enzymes before KT and
      routinely monitoring serologic HBV markers after KT. As only two patients
      experienced HBV reactivation, it is neither possible to define risk factors for
      HBV reactivation nor to evaluate the impact of different immunosuppressants or
      the benefit of prophylactic regimens. Further studies regarding HBV reactivation
      in solid organ transplant recipients are necessary.

PMID- 30295413
TI  - Stanozolol promotes lipid deposition in the aorta through an imbalance in
      inflammatory cytokines and oxidative status in LDLr knockout mice fed a normal
      diet.
AB  - The aim of the study was to evaluate the effect of an anabolic steroid,
      stanozolol, in a model of atherosclerosis and to investigate the involvement of
      the modulation of the inflammatory cytokines and oxidative stress in vascular
      lipid deposition. Low-density lipid receptor-deficient (LDLr-/-) mice were fed a
      standard chow diet and were each week injected subcutaneously either saline
      (control C group) or 20 mg/kg stanozolol (S group). After 8 weeks, the levels of
      cholesterol, oxidized LDL (OxLDL) and cytokines were measured in plasma, lipid
      deposition in aorta was evaluated by en face analysis, and thiobarbituric acid
      reactive substances and oxidation protein were determined in liver. The S group
      demonstrated increases in vascular lipid deposition, triglycerides and non-HDL
      cholesterol levels. Stanozolol increased tumour necrosis factor alpha (TNF-alpha)
      and decreased interleukin-10 as well as increased the TNF-alpha/IL-10 ratio.
      Furthermore, oxidative stress was observed in the S group, as indicated by an
      increase in the plasma OxLDL, as well as by lipid peroxidation and oxidation of
      proteins in the liver. Chronic treatment with stanozolol promoted lipid
      deposition in the LDLr-/- mice that could be attributed to a modification of the
      circulating cytokine levels and systemic oxidative stress. Our results suggest
      that the anabolic steroid stanozolol in the absence of functional LDL receptors
      by increasing systemic inflammation and oxidative stress may increase the risk of
      development and progression of atherosclerosis.

PMID- 30295414
TI  - Corrigendum.

PMID- 30295416
TI  - A Delorme operation for full-thickness complete rectal prolapse - a video
      vignette.

PMID- 30295417
TI  - Reply to Wee.

PMID- 30295418
TI  - Statement on Unproven Therapies for Type 1 Diabetes.

PMID- 30295419
TI  - ISPAD Position Statement on Type 1 Diabetes in Schools.

PMID- 30295420
TI  - The missing heritability of venous thrombosis: what about factor V Leiden
      heterogeneity?

PMID- 30295422
TI  - Persistently Frequent Emergency Department Utilization among Persons with
      Systemic Lupus Erythematosus.
AB  - OBJECTIVE: To evaluate SLE patients who persistently frequent the ED to identify
      opportunities to improve outpatient care. METHODS: We conducted a retrospective
      study of SLE patients who frequented the ED for >=3 visits in a calendar year
      from 2013-2016. Persistent users met criteria for frequent use for at least 2 out
      of the 4 years, and limited users for 1 out of the 4 years. Each ED encounter was
      categorized as; SLE-, infection-, pain- related, or "other". We compared ED use
      between persistent and limited users, and analyzed factors associated with pain
      related encounters among persistent users through multivariate logistic
      regression. RESULTS: We identified 77 participants having 1143 encounters as
      persistent users, and 52 participants having 335 encounters as limited users.
      Persistent users accounted for 77% of ED use by SLE patients who frequented the
      ED. Pain-related ED visits were more common among persistent users (32%) than
      limited users (18%). Among persistent users, most pain-related encounters were
      discharged from the ED (69%) or within 48 hours of admission (20%). Persistent
      users with pain-related encounters accounting for >10% of ED use, were more
      likely to be obese, have fewer comorbid conditions, and be on LTOT. CONCLUSION:
      Pain is major cause of ED use. SLE patients persistently utilizing the ED for
      pain are likely to be non-critically ill, as evidenced by frequent discharges
      from the ED and short stay admissions. SLE patients who persistently frequent the
      ED for pain represent a viable target for interventions to improve outpatient
      quality of care. This article is protected by copyright. All rights reserved.

PMID- 30295423
TI  - Relationship between esophageal abnormalities on fluoroscopic esophagram and
      pulmonary function testing in juvenile systemic sclerosis.
AB  - OBJECTIVE: Juvenile systemic sclerosis (jSSc) is a disabling autoimmune condition
      that affects multiple organs in addition to skin, notably the gastrointestinal
      and pulmonary systems. The relationship between esophageal abnormalities and
      pulmonary disease in jSSc is not well understood. We describe associations
      between radiologic esophageal abnormalities and pulmonary function. METHODS:
      Clinical and radiographic data of children less than 18 years who fulfilled 2007
      Pediatric Rheumatology Provisional Classification Criteria for jSSc between 1994
      and 2016 were reviewed. Fluoroscopic upper gastrointestinal studies (UGI), high
      resolution chest computed tomography (HRCT), and pulmonary function testing
      (PFTs) within 12 months of presentation to Seattle Children's Hospital were
      extracted. RESULTS: 21 children with jSSc (67% female, 8-17 years) were studied.
      Esophageal abnormalities, defined as abnormal esophageal peristalsis and/or bolus
      clearance, were found in 12 patients. Abnormal esophagus on UGI was not
      associated with gastrointestinal or pulmonary symptoms, disease duration, use of
      medications (proton pump inhibitor or immunosuppressant), or specific
      autoantibodies. Compared with patients with a normal esophagus on UGI, children
      with an abnormal esophagus had decreased PFTs: mean FEV1 96% vs. 78% (p=0.03),
      FVC 94% vs. 76% (p=0.02), and VC 95% vs. 76% (p=0.02). Children with an abnormal
      esophagus on UGI had a larger mean esophageal diameter on HRCT, (14.6 mm compared
      to 8.5 mm, p<0.01). CONCLUSION: There was an association between esophageal and
      pulmonary disease in children with jSSc. Esophageal findings on UGI or HRCT,
      despite lack of symptoms, should raise concern for esophageal dysfunction and
      prompt heightened surveillance for concurrent lung disease. This article is
      protected by copyright. All rights reserved.

PMID- 30295421
TI  - SIRT1 deacetylase in aging-induced neuromuscular degeneration and amyotrophic
      lateral sclerosis.
AB  - SIRT1 is an NAD+ -dependent deacetylase that functions in a variety of cells and
      tissues to mitigate age-associated diseases. However, it remains unknown if SIRT1
      also acts to prevent pathological changes that accrue in motor neurons during
      aging and amyotrophic lateral sclerosis (ALS). In this study, we show that SIRT1
      expression decreases in the spinal cord of wild-type mice during normal aging.
      Using mouse models either overexpressing or lacking SIRT1 in motor neurons, we
      found that SIRT1 slows age-related degeneration of motor neurons' presynaptic
      sites at neuromuscular junctions (NMJs). Transcriptional analysis of spinal cord
      shows an overlap of greater than 90% when comparing alterations during normal
      aging with changes during ALS, revealing a substantial upregulation in immune and
      inflammatory response genes and a downregulation of synaptic transcripts. In
      addition, overexpressing SIRT1 in motor neurons delays progression to end-stage
      disease in high copy SOD1G93A mice. Thus, our findings suggest that there are
      parallels between ALS and aging, and interventions to impede aging may also slow
      the progression of this devastating disease.

PMID- 30295424
TI  - Relationship between hip morphology and hip-related patient-reported outcomes in
      young and middle-aged individuals: A population-based study.
AB  - OBJECTIVES: Radiographic measurements of alpha angle and lateral centre edge
      (LCE) angle in the hip joint are important for the diagnosis of femoroacetabular
      syndrome, a potential risk factor for hip osteoarthritis. Our objective was to
      determine if these measurements are associated with hip-related patient-reported
      outcomes (PROs) in young and middle-aged individuals. Methods A stratified random
      sample of Caucasian men and women aged 20-49 years, with and without hip pain,
      was selected using random digit dialling from the population of Metro Vancouver,
      Canada. The alpha and LCE angles were measured bilaterally on x-ray using Dunn
      and AP views, respectively. PROs were measured by the Copenhagen Hip And Groin
      Outcome Score (HAGOS), which has scales for symptoms, pain, daily activities,
      sports, physical activity, and quality of life (QOL). We performed descriptive
      analyses and a regression analysis with restricted cubic splines (RCS), adjusted
      for age and sex and weighted for the sampling design. RESULTS: Data were obtained
      for 500 subjects. The alpha angle distribution was strongly skewed with a mean at
      54O . The LCE angle distribution was symmetric with a mean of 34O . In the RCS
      analysis, the relationship between alpha angle and HAGOS scores was non-linear,
      with higher alpha generally associated with worse HAGOS scores for alpha>60O .
      The associations were statistically significant for symptoms, sports, and QOL. No
      association was found between the LCE angle and HAGOS scales. CONCLUSIONS: In a
      general population sample aged 20-49, we have found an association between alpha
      angle and hip-related patient-reported outcomes. This article is protected by
      copyright. All rights reserved.

PMID- 30295425
TI  - Early Targeted Combination Treatment with csDMARDs Sustains Excellent Long-term
      Outcomes in Rheumatoid Arthritis.
AB  - OBJECTIVE: The short-term outcomes of remission-targeted treatments of rheumatoid
      arthritis (RA) are well-established, but the long-term success of such strategies
      is speculative, as is the role of early add-on biologics. We assessed the 10-year
      outcomes of patients with early RA treated with initial remission-targeted triple
      combination of conventional synthetic disease-modifying antirheumatic-drugs
      (csDMARDs), 7.5 mg prednisolone (PRD) and additional infliximab or placebo
      infusions. METHODS: Ninety-nine patients with early, DMARD-naive RA were treated
      with a triple combination of csDMARDs and PRD, and randomized to double-blindly
      receive either infliximab (FIN-RACo+INFL) or placebo (FIN-RACo+PLA) infusions
      during the first 6 months. After 2 years, the treatment strategies became
      unrestricted, but the treatment goal was strict NEO-RACo remission. At 10 years,
      the clinical and radiographic outcomes and the drug treatments used between 5-10
      years were assessed. RESULTS: Ninety patients (91%) were followed after 2 years,
      43 in the FIN-RACo+INFL and 47 in the FIN-RACo+PLA group. At 10 years, the
      respective proportions of patients in strict NEO-RACo and in DAS28 remissions in
      the FIN-RACo+INFL and FIN-RACo+PLA groups were 46% and 38% (p=0.46), and 82% and
      72% (p=0.29). The mean total Sharp van der Heijde score was 9.8 in the FIN
      RACo+INFL and 7.3 in the FIN-RACo+PLA group (p=0.34). During the 10-year follow
      up 26% of the FIN-RACo+INFL group and 30% of the FIN-RACo+PLA group patients had
      received biologics (p=0.74). CONCLUSION: In early RA, excellent results can be
      maintained up till 10 years in most patients treated with initial combination
      csDMARDs and remission-targeted strategy, regardless of initial
      infliximab/placebo infusions. This article is protected by copyright. All rights
      reserved.

PMID- 30295426
TI  - Sacroiliac Joint Ankylosis In Young Spondyloarthritis Patients Receiving Biologic
      Therapy: Observation of Serial MRI scans.
AB  - OBJECTIVES: To assess the temporal relationship between initiating biologic
      therapy and magnetic resonance imaging (MRI) scores of inflammation and
      structural damage in young patients with spondyloarthritis. METHODS: A local
      adolescent rheumatology database was searched for patients aged 12 - 24 years
      with sacroiliitis on MRI and a clinical diagnosis of enthesitis-related arthritis
      (ERA) or non-radiographic axial spondyloarthritis. Patients treated with tumour
      necrosis factor inhibitor (TNFi) therapy with a minimum of one scan before and
      two after starting TNFi therapy (over >= 2 years) were included. Images of the
      sacroiliac joints were scored for inflammation and structural abnormalities
      (including erosions, fat metaplasia and fusion). The effects of TNFi therapy and
      of time since initiation of TNFi therapy on inflammation and structural
      abnormalities were assessed using a mixed-effects regression analysis. RESULTS:
      Twenty-nine patients aged 12-23 years undergoing TNFi therapy were included.
      Inflammation scores were significantly lower in patients on treatment (P=0.013),
      but there was no significant effect of time from TNFi initiation on inflammation
      (P=0.125). Conversely, there was no significant effect of treatment itself on
      fusion scores (P=0.285), but fusion scores significantly increased with time from
      TNFi initiation (P=0.000). A similar pattern was observed for fat metaplasia.
      Fusion scores did not change in the first year after starting TNFi therapy
      (P=0.108), but were significantly increased at all subsequent time points
      (P=0.000 to 0.001). CONCLUSIONS: TNFi therapy failed to prevent the eventual
      development of joint ankylosis in this cohort, despite a substantial reduction in
      inflammation with TNFi therapy. This article is protected by copyright. All
      rights reserved.

PMID- 30295427
TI  - Effect of physical state on pain mediated through emotional health in rheumatoid
      arthritis.
AB  - OBJECTIVE: Pain is one of the main complaints of patients with rheumatoid
      arthritis (RA). Pain in RA is caused by specific physical changes, such as joint
      destruction, and is therefore used as a disease activity marker. Although pain
      can also be influenced by emotional factors, neither the effect of emotional
      health nor the indirect effect of physical state mediated by emotional health on
      pain has been quantified. METHODS: A total of 548 patients with RA participated.
      Emotional health was assessed using the Hospital Anxiety and Depression Scale
      (HADS). Measures routinely used in practice were used to evaluate physical state
      and pain. To quantify 1) the effects of physical state on emotional health, and
      2) the effects of both physical and emotional health on pain, we used structural
      equation modelling with emotional health, physical state, and pain as latent
      variables. RESULTS: The prevalence of anxiety and depression (HADS score >=8 for
      each) among RA patients was 18.7% and 29.4%, respectively. Emotional health was
      significantly influenced by physical state (beta = 0.21). Pain was affected by
      physical (beta = 0.54) and emotional health (beta = 0.29). The effect of physical
      state on pain was mediated by emotional health, with this mediation effect (beta
      = 0.06) accounting for 10.2% of the total effect. CONCLUSION: The magnitude of
      pain in RA is determined by the mediation effect of emotional health as well as
      the direct physical state. Our findings suggest that emotional factors should be
      taken into account when assessing RA disease activity. This article is protected
      by copyright. All rights reserved.

PMID- 30295428
TI  - Herpes Zoster in Tofacitinib: Risk is Further Increased with Glucocorticoids but
      not Methotrexate.
AB  - BACKGROUND: Increased herpes zoster (HZ) has been observed with janus kinase
      inhibitors such as tofacitinib. However, it is unclear whether concomitant
      methotrexate (MTX) and/or glucocorticoids (GC) confer additional (additive or
      multiplicative) risk. We evaluated HZ risk in tofacitinib users with and without
      MTX and GC. METHODS: Within MarketScan and Medicare data (2011-2016) we
      identified all rheumatologist-diagnosed RA patients initiating tofacitinib (index
      date); demographics and baseline covariates were evaluated in the year prior to
      index date. HZ was ascertained using ICD9/10 codes with anti-viral drug use (+-7
      days). Multivariable (MV) Cox regression was used to evaluate hazard ratios (HRs)
      for HZ in tofacitinib users with and without current concomitant MTX and GC,
      controlling for baseline covariates. RESULTS: We studied 8,030 new tofacitinib
      users (83.3% women). Mean (SD) age was 60.3 (12.6) years. HZ incidence in
      tofacitinib users was numerically lowest in the absence of GC (3.4/100py with
      MTX; 3.7/100py without MTX). An approximately two-fold increased incidence of HZ
      was observed for tofacitinib users receiving either GCs alone (6.0/100 py) or
      both MTX+GCs (6.5/100py). The adjusted HR for HZ in tofacitinib users was
      unchanged (HR=0.99, 95%CI 0.64-1.54) when given only with MTX but was increased
      (HR=1.96, 95%CI 1.33-2.88) for tofacitinib+glucocorticoids. Older age and female
      sex were also risk factors, while prior vaccination was associated with a strong
      trend for lower risk. CONCLUSION: In tofacitinib users, HZ occurred at a rate of
      approximately 4% per year and was further doubled with GC exposure. Concomitant
      MTX did not confer additional risk. Zoster vaccination may decrease risk. This
      article is protected by copyright. All rights reserved.

PMID- 30295429
TI  - Safety and Immunogenicity of Rituximab Biosimilar GP2013 After Switch from
      Reference Rituximab in Patients with Active Rheumatoid Arthritis.
AB  - OBJECTIVES: Comparable clinical efficacy of the rituximab biosimilar GP2013 and
      reference rituximab (RTX) has been established in blinded randomized trials.
      However, when switching from a reference biologic to a biosimilar, potential
      safety implications are often an important consideration. Therefore, this study
      evaluated the safety of switching from reference RTX to rituximab biosimilar
      GP2013, compared with treatment continuation with reference RTX, in patients with
      rheumatoid arthritis (RA). METHODS: In this multinational randomized, double
      blind, parallel-group safety study, 107 patients with RA, who had previously
      received any duration of treatment with reference RTX as part of routine practice
      and who required a continuation of treatment, were randomized to receive either
      GP2013 or to continue reference RTX, both given with methotrexate and folic acid.
      Study assessments included incidence of hypersensitivity, infusion-related and
      anaphylactic reactions, immunogenicity (anti-drug antibodies [ADA]), and general
      safety. RESULTS: Whether patients switched to GP2013 or continued reference RTX,
      the incidences of hypersensitivity (9.4% versus 11.1%, respectively) and infusion
      related reactions (11.3% versus 18.5%, respectively) were similarly low. Only one
      patient in the reference RTX group developed ADA to rituximab after start of
      study treatment. No neutralizing ADAs were observed. ADAs were not associated
      with adverse events (AEs). No clinically meaningful differences in the rate of
      AEs were observed between treatment groups. CONCLUSION: No safety risks were
      detected when patients switched from reference RTX to GP2013. The safety profiles
      of patients in both treatment groups were similar, although the study was not
      powered for statistical safety equivalence testing. This article is protected by
      copyright. All rights reserved.

PMID- 30295430
TI  - Using Physical Activity Trackers in Arthritis Self-Management: A Qualitative
      Study of Patient and Rehabilitation Professional Perspectives.
AB  - OBJECTIVE: To compare and contrast perspectives of patients with arthritis and
      rehabilitation professionals on starting and sustaining use of physical activity
      trackers (PATs). METHODS: We conducted focus groups with patients,
      physiotherapists, and occupational therapists, in Ontario, Alberta or British
      Columbia, Canada. To be eligible, patients reported a diagnosis of inflammatory
      or osteo- arthritis. Rehabilitation professionals reported at least 40% of their
      caseload dedicated to arthritis care. Participants had any level of experience
      with PATs. A thematic analytic approach was used. RESULTS: Three themes were
      identified: 1) Anticipating sharing objective measures of physical activity:
      Participants agreed PATs had potential to improve consultations between patients
      with arthritis and rehabilitation professionals, but were uncertain as to how to
      achieve this potential; 2) Perceived or experienced barriers to start or continue
      using a PAT: Participants shared doubts about whether existing PATs would meet
      specific needs of patients with arthritis, expressing concern about possible
      negative impacts; 3) Bolstering motivation?: While there was agreement that PATs
      could bolster patients' motivation if they were already active, patients and
      rehabilitation professionals felt differently about whether PATs alone would
      motivate patients to start increasing activity levels. CONCLUSION: Our study
      highlights similarities and differences among patient and rehabilitation
      professional perspectives on the potential value and risks of integrating PATs
      into arthritis self-management. Despite agreement about PATs' potential,
      participants were uncertain about how to effectively incorporate these tools to
      enhance patient-clinician consultations and held differing views about whether
      PATs would support patients' motivation to be active. This article is protected
      by copyright. All rights reserved.

PMID- 30295431
TI  - Intrarenal venous flow in cardiorenal syndrome: a shining light into the
      darkness.
AB  - The aim of this case report is to assess the potential role of intrarenal Doppler
      ultrasonography as a non-invasive method to evaluate intrarenal venous flow
      (IRVF) in acute heart failure (AHF) and concomitant renal dysfunction. We report
      a case of an 81-year-old woman with valvular heart disease (previous mitral valve
      replacement) that presented with acutely decompensated heart failure and
      concomitant worsening renal function (WRF). In addition to complete physical
      examination, laboratory analysis, and echocardiography, IRVF was assessed at
      baseline and 48 h after the administration of diuretic treatment. At admission,
      physical examination and echocardiography revealed signs of intravascular
      congestion (jugular venous distension and severely dilated inferior vena cava).
      In addition, a significant increase in serum creatinine from 1.23 to 1.81 mg/dL
      was noted without signs of hypoperfusion at clinical evaluation. At baseline,
      intrarenal Doppler ultrasonography showed a monophasic IRVF pattern indicating a
      severely elevated interstitial renal pressure. After aggressive decongestion, a
      dynamic behaviour was found in IRVF changing from monophasic to biphasic pattern
      in parallel with an improvement in clinical parameters and renal function (serum
      creatinine changed from 1.81 to 1.44 mg/dL). In this case of a patient with AHF
      and WRF, IRVF changed after aggressive decongestion in agreement with clinical
      evolution. According to these findings, this technique could provide valuable
      information for identifying patients with a 'congestion kidney failure'
      phenotype. Further studies are needed confirming this observation and evaluating
      the potential role of this technique for guiding decongestive therapy in patients
      with AHF and WRF.

PMID- 30295432
TI  - Central sensitisation in knee osteoarthritis: Relating pre-surgical brainstem
      neuroimaging and PainDETECT based patient stratification to arthroplasty outcome.
AB  - OBJECTIVES: The neural mechanisms of pain in knee OA are not fully understood:
      some patients have neuropathic-like pain, associated with central sensitisation.
      We aimed to identify central sensitisation using neuroimaging and PainDETECT, and
      relate it to post-arthroplasty outcome. METHODS: Patients awaiting arthroplasty
      underwent quantitative sensory testing, psychological assessment and functional
      neuroimaging (fMRI). fMRI was conducted during punctate (n=24) and cold pain
      stimulation (n=20) to the affected knee. Post-operative outcome was measured
      using: Oxford Knee Score; moderate to severe long-term pain after arthroplasty
      and a range of pain-related questionnaires. RESULTS: Patients with neuropathic
      like pain pre-surgery, identified using PainDETECT, reported significantly higher
      pain to punctate and cold stimuli, near the affected joint. In these patients and
      when compared to those without neuropathic-like pain, neural activity was
      significantly lower in the rostral anterior cingulate cortex and higher in the
      rostral ventromedial medulla (RVM) during punctate stimulation, with significant
      functional connectivity between these two areas. Pre-operative neuropathic-like
      pain and higher neural activity in the RVM was associated with moderate to severe
      long-term pain after arthroplasty. CONCLUSION: The psychophysical and
      neuroimaging data suggest that a subset of OA patients have centrally mediated
      pain sensitisation. This is likely due to supraspinally mediated reductions in
      inhibition, and increases in facilitation of nociceptive signaling, and was
      associated with a worse outcome following arthroplasty. The neurobiological
      confirmation of central sensitisation in patients with features of neuropathic
      pain, identified using PainDETECT, provides further support for the investigation
      of such bed-side measures for patient stratification to better predict post
      surgical outcome. This article is protected by copyright. All rights reserved.

PMID- 30295433
TI  - Febuxostat does not increase all-cause mortality and cardiovascular mortality
      compared with placebo from FEATHER study.
AB  - I have carefully read with great interest the article, entitled "Implications of
      the cardiovascular safety of febuxostat and allopurinol in patients with gout and
      cardiovascular morbidities (CARES) trial and associated FDA public safety alert"
      by Choi H, et al., recently published in the last issue of Arthritis &
      Rheumatology.(1) The article reviewed the recent article in the New England
      Journal of Medicine, entitled "Cardiovascular Safety of Febuxostat or Allopurinol
      in Patients with Gout (CARES trial)" by William B et al..(2) I mostly agree with
      the context of the review article by Choi H, et al.. CARES trial first reported
      that all-cause mortality and cardiovascular mortality are higher with febuxostat
      than with allopurinol. However, the study has not proven that febuxostat
      increased all-cause mortality and cardiovascular mortality compared with placebo.
      This article is protected by copyright. All rights reserved.

PMID- 30295434
TI  - Long-Term Safety of Rituximab in Rheumatoid Arthritis: Analysis From the SUNSTONE
      Registry.
AB  - OBJECTIVE: To evaluate the long-term safety of rituximab in an observational
      cohort of patients with rheumatoid arthritis (RA) who had an inadequate response
      to >= 1 antitumor necrosis factor therapies in the United States (SUNSTONE
      Registry). METHODS: In this prospective, observational cohort study, patients
      received rituximab according to their physician's standard practice and were
      evaluated at standard-of-care follow-up visits at least every 6 months. The
      primary outcome was the incidence of protocol-defined significant infections.
      Secondary outcomes included serious adverse events potentially associated with
      rituximab, cardiovascular or thrombotic (CVT) events, seizures, deaths and
      pregnancies. Posthoc analyses assessed outcomes by concomitant medication use.
      RESULTS: Overall, 989 patients (safety-evaluable population) received >= 1 dose
      of rituximab, with a total follow-up of 3844 patient-years (PYs; mean duration,
      3.9 years). In total, 341 significant infections occurred in 197 patients
      (19.9%). The incidence rates (95% CI) for significant infections, CVT events, and
      seizures were 8.87 (7.98, 9.86), 1.95 (1.56, 2.45), and 0.18 (0.09, 0.38) per 100
      PYs, respectively. The incidence of significant infections did not increase with
      time or with cumulative rituximab exposure. During the study, 64 patients died
      (crude mortality [95% CI]: 1.66 per 100 PYs [1.30, 2.13]). The most common causes
      of death were infections (19 patients), malignancy (14), and cardiovascular
      events (13). Eight pregnancies were reported in 7 patients. CONCLUSION: In
      patients with RA treated with rituximab for up to 5 years, the rates of
      significant infections were stable over time and higher in patients who received
      long-term systemic steroid treatment. This article is protected by copyright. All
      rights reserved.

PMID- 30295435
TI  - Chronic inflammation in RA: mediator of skeletal muscle pathology and physical
      impairment.
AB  - This review focuses on the effects of chronic systemic inflammation on skeletal
      muscle and its downstream effect on physical function in individuals with
      rheumatoid arthritis (RA). The importance of skeletal muscle in the regulation of
      whole-body glucose and lipid metabolism, and the benefits and barriers to
      physical activity and exercise training are highlighted. Finally, we identify
      knowledge gaps that may be important for the development of both pharmacologic
      and non-pharmacologic interventions (e.g. proper exercise regimens) to protect
      individuals with RA from physical impairment. This article is protected by
      copyright. All rights reserved.

PMID- 30295436
TI  - Authors' Reply to Letter to the Editor.
AB  - We appreciate Dr. Kuwabara's sharing FEATHER study data in relation to our
      article2 about the cardiovascular safety of febuxostat and allopurinol in
      patients with gout and cardiovascular morbidities (CARES) trial. As pointed out,
      we agree that the FEATHER study's overall cardiovascular (CV) disease outcome
      results4 tended to be consistent with the CARES trial findings, although its
      sample size was >10 time smaller than the CARES trial and underpowered for that
      purpose. The author states no difference of CV mortality, but no data are
      provided, although the number of CV deaths would be less than the overall CV
      event rates (4/219 in febuxostat and 7/222 in placebo).4 To that end, these data
      appear to add minimally to the causal inference about the CV impact of
      febuxostat. This article is protected by copyright. All rights reserved.

PMID- 30295437
TI  - Early urine electrolyte patterns in patients with acute heart failure.
AB  - AIMS: We conducted a prospective study of emergency department (ED) patients with
      acute heart failure (AHF) to determine if worsening HF (WHF) could be predicted
      based on urinary electrolytes during the first 1-2 h of ED care. Loop diuretics
      are standard therapy for AHF patients. A subset of patients hospitalized for AHF
      will develop a blunted natriuretic response to loop diuretics, termed diuretic
      resistance, which often leads to WHF. Early detection of diuretic resistance
      could facilitate escalation of therapy and prevention of WHF. METHODS AND
      RESULTS: Patients were eligible if they had an ED AHF diagnosis, had not yet
      received intravenous diuretics, had a systolic blood pressure > 90 mmHg, and were
      not on dialysis. Urine electrolytes and urine output were collected at 1, 2, 4,
      and 6 h after diuretic administration. Worsening HF was defined as clinically
      persistent or WHF requiring escalation of diuretics or administration of
      intravenous vasoactives after the ED stay. Of the 61 patients who qualified in
      this pilot study, there were 10 (16.3%) patients who fulfilled our definition of
      WHF. At 1 h after diuretic administration, patients who developed WHF were more
      likely to have low urinary sodium (9.5 vs. 43.0 mmol; P < 0.001) and decreased
      urine sodium concentration (48 vs. 80 mmol/L; P = 0.004) than patients without
      WHF. All patients with WHF had a total urine sodium of <35.4 mmol at 1 h (100%
      sensitivity and 60% specificity). CONCLUSIONS: One hour after diuretic
      administration, a urine sodium excretion of <35.4 mmol was highly suggestive of
      the development of WHF. These relationships require further testing to determine
      if early intervention with alternative agents can prevent WHF.

PMID- 30295438
TI  - A 36-Year-Old Man with Renal Failure, Fevers, and Hypocomplementemia.
AB  - A 36-year-old man with recently diagnosed renal injury presented with fevers and
      dental pain. For 15 months the patient had decreased appetite and malaise. He had
      missed work due to his symptoms. Two months prior, cough and ongoing malaise
      prompted an Emergency Department visit. At that time, routine laboratory
      evaluation revealed blood urea nitrogen 105 mg/dL and creatinine 7.01 mg/dL with
      estimated glomerular filtration rate of 9 mL/min/1.73m. A work-up was initiated
      and renal biopsy was performed. A 16-day trial of oral prednisone was prescribed
      for presumed acute interstitial nephritis. This article is protected by
      copyright. All rights reserved.

PMID- 30295439
TI  - The sex-specific influence of quadriceps weakness on worsening patellofemoral and
      tibiofemoral cartilage damage: the MOST Study.
AB  - OBJECTIVE: Reports on quadriceps weakness as a risk factor for incident and
      progressive knee osteoarthritis are conflicting, potentially due to differing
      effects of muscle strength on patellofemoral and tibiofemoral compartments. This
      study aimed to examine the sex-specific relation of quadriceps strength to
      worsening patellofemoral and tibiofemoral cartilage damage over 84-months.
      METHODS: The Multicenter Osteoarthritis Study (MOST) is a cohort study of
      individuals with or at risk for knee osteoarthritis. Maximal quadriceps strength
      was assessed at baseline. Cartilage damage was semi-quantitatively assessed by
      magnetic resonance images (MRIs) at baseline and 84-month follow-up using the
      Whole-Organ MRI Score (WORMS). Worsening patellofemoral and tibiofemoral
      cartilage damage was defined as any WORMS score increase in each subregion within
      medial and lateral compartments separately. Logistic regression with generalised
      estimating equations was used to assess the sex-specific relation of quadriceps
      strength to worsening cartilage damage. RESULTS: 1,018 participants (mean age
      61+/-8 years, and BMI 29.3+/-4.5 kg/m2 ; 64% female) were included. Quadriceps
      weakness increased the risk of worsening lateral patellofemoral cartilage damage
      in women (risk ratio for lowest vs. highest quartile of strength: 1.50 (95%
      confidence interval: 1.03, 2.20); linear trend p=0.007) but not in men. There was
      generally no association between quadriceps weakness and worsening cartilage
      damage in the medial or lateral tibiofemoral compartment for either women or men.
      CONCLUSION: Low quadriceps strength increased the risk of worsening cartilage
      damage in the lateral patellofemoral joint of women suggesting that optimising
      quadriceps strength may help prevent worsening of structural damage in the
      patellofemoral joint in women. This article is protected by copyright. All rights
      reserved.

PMID- 30295440
TI  - A traveller's wart: tungiasis.

PMID- 30295442
TI  - Gynecomastia following isotretinoin treatment: a rare endocrine side effect.

PMID- 30295441
TI  - Sannino-Barduagni-Bottoni syndrome: a case report and review of the literature.

PMID- 30295443
TI  - Combination of permethrin 5% cream with liquid cleanser containing Chlorhexidine,
      agents from Szechuan peppers, menthol and camphor in scabies treatment results in
      high levels of subject satisfaction, favorable tolerability and less pruritus.

PMID- 30295444
TI  - A case of basal cell carcinoma in a young patient with Incontinentia Pigmenti.

PMID- 30295445
TI  - Nevus spilus in neurofibromatosis type 1: a single center experience.

PMID- 30295446
TI  - Dermoscopical and pathological findings in pseudoxanthoma elasticum-like
      papillary dermal elastolysis.

PMID- 30295447
TI  - Nivolumab induced morphea.

PMID- 30295448
TI  - Characterization of comorbid conditions burdening hidradenitis suppurativa: a
      multicentric observational study.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, disabling, inflammatory
      skin disorder that primarily affects the hair follicle localized at the apocrine
      gland-bearing areas of the body, including axillary, inguinal, buttocks, and
      anogenital areas, and it may be associated with a wide array of comorbid
      conditions. This study aimed to described comorbid conditions affecting HS
      patients and to detect any correlation with disease severity. METHODS: Analyzing
      clinic database, we included all charts of patients visited at the HS outpatient
      clinic of three University Dermatologic Departments in order to describe
      demographic data, anthropometric measures, disease features, personal habits,
      clinical history, and presence of comorbidities. RESULTS: Two hundred thirty-four
      patients, mostly females (62%), were enrolled in this study. Based on Hurley
      staging classification 41% of patients were classified as Hurley Stage I, 43.0%
      as Hurley II, and 16% Hurley III, with a mean mSartorius score value of 24.7 (SD:
      +/-19.39) and a mean AISI score value of 12.5 (SD: +/-11.93). The most frequently
      observed comorbidities were: obesity (26.1%), polycystic ovary syndrome (PCOS)
      (13.8% of the overall study population and 22.3% of females), hypertension
      (11.9%), dyslipidemia (9.9%), type II diabetes (9.5%), thyroid disorders (9.1%),
      nervous system disorders (7.1%), acne (6.7%), metabolic syndrome (4.4%), and
      Crohn's disease (3.6%). Obesity represented a key-comorbid condition increasing
      the likelihood of having more severe HS and PCOS (odds ratio 3.35 and 3.74,
      respectively). CONCLUSIONS: HS is associated with a variety of comorbid
      conditions that should be considered to perform targeted routine screening and to
      improve HS management.

PMID- 30295449
TI  - Two rare disease in the same patient: neurofibromatosis type 1 and Madelung's
      disease.

PMID- 30295450
TI  - Low Interface Energies Tune the Electrochemical Reversibility of Tin Oxide
      Composite Nanoframes as Lithium-Ion Battery Anodes.
AB  - The conversion reaction of lithia can push up the capacity limit of tin oxide
      based anodes. However, the poor reversibility limits the practical applications
      of lithia in lithium-ion batteries. The latest reports indicate that the
      reversibility of lithia has been appropriately promoted by compositing tin oxide
      with transition metals. The underlying mechanism is not revealed. To design
      better anodes, we studied the nanostructured metal/Li2O interfaces through atomic
      scale modeling and proposed a porous nanoframe structure of Mn/Sn binary oxides.
      The first-principles calculation implied that because of a low interface energy
      of metal/Li2O, Mn forms smaller particles in lithia than Sn. Ultrafine Mn
      nanoparticles surround Sn and suppress the coarsening of Sn particles. Such a
      composite design and the resultant interfaces significantly enhance the
      reversible Li-ion storage capabilities of tin oxides. The synthesized nanoframes
      of manganese tin oxides exhibit an initial capacity of 1620.6 mA h g-1 at 0.05 A
      g-1. Even after 1000 cycles, the nanoframe anode could deliver a capacity of
      547.3 mA h g-1 at 2 A g-1. In general, we demonstrated a strategy of
      nanostructuring interfaces with low interface energy to enhance the Li-ion
      storage capability of binary tin oxides and revealed the mechanism of property
      enhancement, which might be applied to analyze other tin oxide composites.

PMID- 30295451
TI  - Self-Regenerating Soft Biophotovoltaic Devices.
AB  - This paper describes the fabrication of soft, stretchable biophotovoltaic devices
      that generate photocurrent from photosystem I (PSI) complexes that are self
      assembled onto Au electrodes with a preferred orientation. Charge is collected by
      the direct injection of electrons into the Au electrode and the transport of
      holes through a redox couple to liquid eutectic gallium-indium (EGaIn) electrodes
      that are confined to microfluidic pseudochannels by arrays of posts. The
      pseudochannels are defined in a single fabrication step that leverages the non
      Newtonian rheology of EGaIn. This strategy is extended to the fabrication of
      reticulated electrodes that are inherently stretchable. A simple shadow
      evaporation technique is used to increase the surface area of the Au electrodes
      by a factor of approximately 106 compared to planar electrodes. The power
      conversion efficiency of the biophotovoltaic devices decreases over time,
      presumably as the PSI complexes denature and/or detach from the Au electrodes.
      However, by circulating a solution of active PSI complexes the devices self
      regenerate by mass action/self-assembly. These devices leverage simple
      fabrication techniques to produce complex function and prove that photovoltaic
      devices comprising PSI can retain the ability to regenerate, one of the most
      important functions of photosynthetic organisms.

PMID- 30295453
TI  - Progressive Micromodulation of Interlayer Coupling in Stacked WS2/WSe2
      Heterobilayers Tailored by a Focused Laser Beam.
AB  - When a vertically stacked heterobilayer comprising of a WSe2 monolayer on a WS2
      monolayer is first fabricated, the heterobilayer behaves like two independent
      monolayers because of the presence of a large interlayer separation. However,
      after the stacked heterobilayer is subjected to a focused laser treatment, the
      interlayer separation between the two monolayers becomes progressively reduced
      which transforms the WS2/WSe2 heterostructure from the noncoupling to the
      strongly coupling regime. This strong coupling induces the charge transfer
      between two layers and thus lowers the exciton recombination rate in the
      individual layer. This changes the optical properties of the heterobilayer from a
      fluorescence-active species into one where the fluorescence is quenched. The
      focused laser beam scanning method is therefore able to serve as a localized
      annealing tool to progressively modulate the interlayer separation and enable the
      micropatterning of the heterobilayer to achieve distinct regions with different
      degrees of fluorescence quenching. Systematic studies are carried out to gain an
      insight into the mechanism involved in the onset of the interlayer coupling in
      the material. Our method is also successfully extended to a WS2/WS2 homobilayer
      structure.

PMID- 30295452
TI  - Highly Sensitive Color Tunablility by Scalable Nanomorphology of a Dielectric
      Layer in Liquid-Permeable Metal-Insulator-Metal Structure.
AB  - A liquid-permeable concept in a metal-insulator-metal (MIM) structure is proposed
      to achieve highly sensitive color-tuning property through the change of the
      effective refractive index of the dielectric insulator layer. A semicontinuous
      top metal film with nanoapertures, adopted as a transreflective layer for MIM
      resonator, allows to tailor the nanomorphology of a dielectric layer through
      selective etching of the underneath insulator layer, resulting in nanopillars and
      hollow voids in the insulator layer. By allowing outer mediums to enter into the
      hollow voids of the dielectric layer, such liquid-permeable MIM architecture
      enables to achieve the wavelength shift as large as 323.5 nm/RIU in the visible
      range, which is the largest wavelength shift reported so far. Our liquid
      permeable approaches indeed provide dramatic color tunablility, a real-time
      sensing scheme, long-term durability, and reproducibility in a simple and
      scalable manner.

PMID- 30295454
TI  - Ultra-Small Platinum Nanoparticles Encapsulated in Sub-50 nm Hollow Titania
      Nanospheres for Low-Temperature Water-Gas Shift Reaction.
AB  - Ultra-small platinum nanoparticles loaded over titania is a promising catalyst
      for the low-temperature water-gas shift (WGS) reaction and shows the potential to
      work in a mobile hydrogen fuel cell system. Their precise size engineering (<3
      nm) and reliable stabilization remain challenging. To address these issues, we
      report a reverse-micelle synthesis approach, which affords uniform ultra-small
      platinum nanoparticles (tunable in ~1.0-2.6 nm) encapsulated in hollow titania
      nanospheres with a shell thickness of only ~3-5 nm and an overall diameter of
      only ~32 nm. The Pt@TiO2 yolk/shell nanostructured catalysts display
      extraordinary stability and monotonically increasing activity with the decreasing
      size of the Pt nanoparticles in the WGS. The size-dependent variation in the
      electronic property of the Pt nanoparticles and the reducible oxide encapsulation
      that prevents the Pt nanoparticles from sintering are ascribed as the main
      reasons for the excellent catalytic performance.

PMID- 30295455
TI  - Walnut-like Transition Metal Carbides with Three-Dimensional Networks by a
      Versatile Electropolymerization-Assisted Method for Efficient Hydrogen Evolution.
AB  - Mo2C@NPC (N,P-doped carbon) electrocatalysts are developed on carbon cloth (CC)
      as binder-free cathodes for efficient hydrogen evolution through a facile route
      of electropolymerization followed by pyrolysis. Electropolymerization of pyrrole
      to form polypyrrole occurs with the homogeneous incorporation of PMo12, driven by
      Coulombic force between the positively charged polymer backbone and PMo12 anions.
      This electrochemical synthesis is easily scaled up, requiring neither complex
      instrumentation nor an intentionally added electrolyte (PMo12 also acts as an
      electrolyte). After pyrolysis, the resultant Mo2C@NPC/CC electrode exhibits a
      unique interconnected walnut-like porous structure, which ensures strong adhesion
      between the active material and the substrate and favors electrolyte penetration
      into the electrocatalyst. This method is effective with other monomers such as
      aniline and is readily extended to fabricate other metal carbide electrodes such
      as WC@NPC/CC. These carbide electrodes exhibit high catalytic performance for
      hydrogen production, for example, WC@NPC/CC can deliver an unprecedented current
      density of 600 mA cm-2 at an overpotential of only 200 mV either in an acidic or
      an alkaline solution. Considering the simplicity, scalability, and versatility of
      the synthetic method, the unique electrode structure, and the excellent catalysis
      performance, this study opens up new avenues for the design of various novel
      binder-free metal carbide cathodes based on electropolymerization.

PMID- 30295456
TI  - Polydopamine-Derived Nitrogen-Doped Carbon-Covered Na3V2(PO4)2F3 Cathode Material
      for High-Performance Na-Ion Batteries.
AB  - Nitrogen-doped carbon-covered Na3V2(PO4)2F3 (NVPF/C-PDPA) composites have been
      successfully prepared by self-polymerization of dopamine on the NVPF surface and
      subsequent sintering. The X-ray diffraction results show that the NVPF/C-PDPA has
      good crystallinity and introducing dopamine does not affect the lattice structure
      of NVPF. The high-resolution transmission electron microscopy, high-angle annular
      dark-field images, and energy dispersive X-ray spectroscopy analyses reveal that
      the NVPF/C-PDPA particles are covered by a complete and uniform covering layer,
      which is effective at preventing corrosion of NVPF in the electrolyte to greatly
      increase cycling stability. Furthermore, N-doping into the carbon layer can
      produce additional active sites to improve the capacity especially the rate
      capacity. Such a NVPF/C-PDPA electrode delivers a remarkable rate capacity (98.0
      mA h g-1 at 10 C) and superior cycle performance (~95.8% capacity retention at 10
      C after 800 cycles). We believe that this work may be beneficial for accelerating
      the development of high-performance electrode materials and the commercialization
      of Na-ion batteries.

PMID- 30295457
TI  - Gold Nanoparticles Biosynthesized and Functionalized Using a Hydroxylated
      Tetraterpenoid Trigger Gene Expression Changes and Apoptosis in Cancer Cells.
AB  - Understanding the synthetic mechanisms and cell-nanoparticle interactions of
      biosynthesized and functionalized gold nanoparticles (AuNPs) using natural
      products is of great importance for developing their applications in
      nanomedicine. In this study, we detailed the biotransformation mechanism of
      Au(III) into AuNPs using a hydroxylated tetraterpenoid deinoxanthin (DX) from the
      extremophile Deinococcus radiodurans. During the process, Au(III) was rapidly
      reduced to Au(I) and subsequently reduced to Au(0) by deprotonation of the
      hydroxyl head groups of the tetraterpenoid. The oxidized form, deprotonated 2
      ketodeinoxanthin (DX3), served as a surface-capping agent to stabilize the AuNPs.
      The functionalized DX-AuNPs demonstrated stronger inhibitory activity against
      cancer cells compared with sodium citrate-AuNPs and were nontoxic to normal
      cells. DX-AuNPs accumulated in the cytoplasm, organelles, and nuclei, and induced
      reactive oxygen species generation, DNA damage, and apoptosis within MCF-7 cancer
      cells. In the cells treated with DX-AuNPs, 374 genes, including RRAGC gene, were
      upregulated; 135 genes, including the genes encoding FOXM1 and NR4A1, were
      downregulated. These genes are mostly involved in metabolism, cell growth, DNA
      damage, oxidative stress, autophagy, and apoptosis. The anticancer activity of
      the DX-AuNPs was attributed to the alteration of gene expression and induction of
      apoptosis. Our results provide significant insight into the synthesis mechanism
      of AuNPs functionalized with natural tetraterpenoids, which possess enhanced
      anticancer potential.

PMID- 30295458
TI  - Paper-Derived Flexible 3D Interconnected Carbon Microfiber Networks with
      Controllable Pore Sizes for Supercapacitors.
AB  - Heteroatom-doped three-dimensional (3D) carbon fiber networks have attracted
      immense interest because of their extensive applications in energy-storage
      devices. However, their practical production and usage remain a great challenge
      because of the costly and complex synthetic procedures. In this work, flexible B,
      N, and O heteroatom-doped 3D interconnected carbon microfiber networks (BNOCs)
      with controllable pore sizes and elemental contents were successfully synthesized
      via a facile one-step "chemical vapor etching and doping" method using cellulose
      made paper, the most abundant and cost-effective biomass, as an original network
      frame precursor. Under a rational design, the BNOCs exhibited interconnected
      microfiber-network structure as expressways for electron transport, spacious
      accessible surface area for charge accumulation, abundant mesopores and
      macropores for rapid inner-pore ion diffusion, and lots of functional groups for
      additional pseudocapacitance. Being applied as binder-free electrodes for
      supercapacitors, BNOC-based supercapacitors not only revealed a high specific
      capacitance of 357 F g-1, a high capacitance retention of 150 F g-1 at 200 A g-1,
      a high energy density of 12.4 W h kg-1, and a maximum power density of 300.6 kW
      kg-1 with an aqueous electrolyte in two-electrode configuration but also
      exhibited a high specific capacitance of up to 242.4 F g-1 in an all-solid-state
      supercapacitor.

PMID- 30295459
TI  - On the Feasibility of Practical Mg-S Batteries: Practical Limitations Associated
      with Metallic Magnesium Anodes.
AB  - Rechargeable magnesium batteries (RMBs) have attracted a lot of attention in
      recent decades due to the theoretical properties of these systems in terms of
      energy density, safety, and price. Nevertheless, to date, fully rechargeable
      magnesium battery prototypes with sufficient longevity and reversibility were
      realized only with low voltage and low capacity intercalation cathode materials
      based on Cheverel phases. The community is therefore actively looking for high
      capacity cathodes that can work with metallic magnesium anodes in viable RMB
      systems. One of the most promising cathode materials, in terms of very high
      theoretical specific capacity, is, naturally, sulfur. A number of recent works
      studied the electrochemical performances of rechargeable sulfur cathodes in RMB,
      with success to some extent on the cathode side. Nevertheless, as known from the
      lithium-sulfur rechargeable battery systems, the formation of soluble
      polysulfides during discharge affects strongly the behavior of the anode side. In
      this article and the work it describes, we focus on  soluble polysulfides impact
      on Mg-S electrochemichal systems. We carefully designed herein conditions that
      mimic the Mg-S battery prototypes containing balanced Mg and elemental sulfur
      electrodes. Under these conditions, we extensively studied the Mg anode behavior.
      The study shows that when elemental sulfur cathodes are discharged in the Mg-S
      cells containing electrolyte solutions in which Mg anodes behave reversibly, the
      polysulfide species thus formed migrate to the anode and eventually fully
      passivate it by the formation of very stable surface layers. The work involved
      electrochemical, spectroscopic, and microscopic studies. The present study
      clearly shows that to realize practical rechargeable Mg-S batteries, the
      transport of any sulfide moieties from the sulfur cathode to the magnesium anode
      has to be completely avoided. Such a condition is mandatory for the operation of
      secondary Mg-S batteries.

PMID- 30295460
TI  - High Energy Density, Super-Deformable, Garment-Integrated Microsupercapacitors
      for Powering Wearable Electronics.
AB  - Lightweight energy storage technologies are integral for powering emerging
      wearable health monitors and smart garments. In-plane, interdigitated
      microsupercapacitors (MSCs) hold the greatest promise to be integrated into
      wearable electronics because of their miniaturized footprint, as compared to
      conventional, multilayered supercapacitors and batteries. Constructing MSCs
      directly on textiles, while retaining the fabric's pliability and tactile
      quality, will provide uniquely wearable energy storage systems. However, relative
      to plastic-backed or paper-based MSCs, garment-integrated MSCs are underreported.
      The challenge lies in creating electrochemically active fiber electrodes that can
      be turned into MSCs. We report a facile vapor deposition and sewing sequence to
      create rugged textile MSCs. Conductive threads are vapor-coated with a stably p
      doped conducting polymer film and then sewn onto a stretchy textile to form three
      dimensional, compactly aligned electrodes with the electrode dimensions defined
      by the knit structure of the textile backing. The resulting solid-state device
      has an especially high areal capacitance and energy density of 80 mF/cm2 and 11
      MUW h/cm2 with a polymer gel electrolyte, and an energy density of 34 MUW h/cm2
      with an ionic liquid electrolyte, sufficient to power contemporary iterations of
      wearable biosensors. These textile MSCs are also super deformable, displaying
      unchanging electrochemical performance after fully rolling-up the device.

PMID- 30295461
TI  - DIA+: A Data-Independent Acquisition Method Combining Multiple Precursor Charges
      to Improve Peptide Signal.
AB  - Data-independent acquisition methods that acquire fragment ions from virtually
      any peptide in a sample have expanded the benefits of low-throughput targeted
      proteomics to proteome-wide analyses. While these methods have increased the
      reproducibility of peptide quantification across multiple samples, their
      sensitivity is still limited, and the quantification of complete proteomes
      remains a challenge. Here we present DIA+, a DIA method that combines signals
      from identical peptides with different charge states, resulting in improved
      signal-to-noise, additional number of fragments, and therefore in a higher number
      of identified and quantified peptides in complex samples.

PMID- 30295462
TI  - Nucleic Acid Detection by a Target-Assisted Proximity Proteolysis Reaction.
AB  - Nucleic acid analysis plays an important role in diagnosing diseases as well as
      understanding biology. Despite advances in technology, there is still a need to
      develop a rapid and simple method to detect specific nucleic acids, especially in
      remote locations and low-resource cases. Here, we proposed a proximity
      proteolysis reaction in which the reaction between protease and zymogen is
      enhanced in the presence of a target molecule. The pair of proteins was site
      specifically modified with oligonucleotides, and the conjugates were used to
      develop a method of detecting nucleic acids. Target DNA and RNA could be detected
      in less than 1 h at sub-nanomolar concentrations based on an absorbance signal.
      The assay method was resistant to interference by biological matrixes, and its
      sensitivity could be improved when combined with an isothermal nucleic acid
      amplification method. The results demonstrated the feasibility of this proximity
      proteolysis reaction as a new platform technology for detecting specific nucleic
      acid sequences.

PMID- 30295463
TI  - Electronic Structure Tunability by Periodic meta-Ligand Spacing in One
      Dimensional Organic Semiconductors.
AB  - Designing molecular organic semiconductors with distinct frontier orbitals is key
      for the development of devices with desirable properties. Generating defined
      organic nanostructures with atomic precision can be accomplished by on-surface
      synthesis. We use this "dry" chemistry to introduce topological variations in a
      conjugated poly( para-phenylene) chain in the form of meta-junctions. As
      evidenced by STM and LEED, we produce a macroscopically ordered, monolayer thin
      zigzag chain film on a vicinal silver crystal. These cross-conjugated
      nanostructures are expected to display altered electronic properties, which are
      now unraveled by highly complementary experimental techniques (ARPES and STS) and
      theoretical calculations (DFT and EPWE). We find that meta-junctions dominate the
      weakly dispersive band structure, while the band gap is tunable by altering the
      linear segment's length. These periodic topology effects induce significant loss
      of the electronic coupling between neighboring linear segments leading to partial
      electron confinement in the form of weakly coupled quantum dots. Such periodic
      quantum interference effects determine the overall semiconducting character and
      functionality of the chains.

PMID- 30295464
TI  - Simultaneous Monitoring of Mitochondrial Temperature and ATP Fluctuation Using
      Fluorescent Probes in Living Cells.
AB  - Real-time monitoring of the distribution of energy released during oxidative
      phosphorylation (OXPHOS) in living cells would advance the understanding of
      metabolic pathways and cell biology. However, the relationship between
      intracellular temperature and ATP fluctuation during the OXPHOS process is rarely
      studied due to the limitation of the sensing approach. Novel fluorescent polymer
      probes were developed for accurate simultaneous measurements of intracellular
      temperature and ATP. Utilizing the fluorescence imaging techniques, it was
      demonstrated for the first time that the temperature in mitochondria increased
      2.4  degrees C and the ATP fluctuation level simultaneously decreased 75% within
      2 min during the OXPHOS process. Moreover, the resultant fluorescent polymer
      probes had good performance and properties for mitochondrial targeting, providing
      an effective way for investigating mechanisms by which energy is released during
      the OXPHOS process.

PMID- 30295465
TI  - SET-LRP in Biphasic Mixtures of the Nondisproportionating Solvent
      Hexafluoroisopropanol with Water.
AB  - The fluorinated alcohol 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) is an especially
      effective solvent for solubilizing a wide range of polymers. However, the
      performance of HFIP as SET-LRP solvent has classically been questioned due to its
      poor Cu(I)X disproportionating properties. Taking advantage of the fast and
      quantitative disproportionation of Cu(I)X in water, SET-LRP in organic
      solvent/water mixtures rids the organic solvent of mediating this fundamental
      event. Here, the Cu(0) wire-catalyzed SET-LRP synthesis of well-defined
      poly(methyl acrylate)s and poly(butyl acrylate)s with narrow molecular weight
      distribution and near perfect bromine chain end functionality is reported in
      HFIP/water mixtures. The results reported here support the potential of
      HFIP/water mixtures in the preparation of more complex architectures including
      polymers with dual control over molecular weight and tacticity. Since HFIP is
      also a classic solvent for the denaturation of proteins this SET-LRP system is
      also expected to find applications in the grafting of protein.

PMID- 30295466
TI  - Glutaminase Affects the Transcriptional Activity of Peroxisome Proliferator
      Activated Receptor gamma (PPARgamma) via Direct Interaction.
AB  - Phosphate-activated glutaminases catalyze the deamidation of glutamine to
      glutamate and play key roles in several physiological and pathological processes.
      In humans, GLS encodes two multidomain splicing isoforms: KGA and GAC. In both
      isoforms, the canonical glutaminase domain is flanked by an N-terminal region
      that is folded into an EF-hand-like four-helix bundle. However, the splicing
      event replaces a well-structured three-repeat ankyrin domain in KGA with a
      shorter, unordered C-terminal stretch in GAC. The multidomain architecture, which
      contains putative protein-protein binding motifs, has led to speculation that
      glutaminases are involved in cellular processes other than glutamine metabolism;
      in fact, some proteins have been identified as binding partners of KGA and the
      isoforms of its paralogue gene, GLS2. Here, a yeast two-hybrid assay identified
      nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) as
      a new binding partner of the glutaminase. We show that KGA and GAC directly bind
      PPARgamma with a low-micromolar dissociation constant; the interaction involves
      the N-terminal and catalytic domains of glutaminases as well as the ligand
      binding domain of the nuclear receptor. The interaction occurs within the
      nucleus, and by sequestering PPARgamma from its responsive element DR1, the
      glutaminases decreased nuclear receptor activity as assessed by a luciferase
      reporter assay. Altogether, our findings reveal an unexpected glutaminase-binding
      partner and, for the first time, directly link mitochondrial glutaminases to an
      unanticipated role in gene regulation.

PMID- 30295467
TI  - Transition Metal Complexes and Photodynamic Therapy from a Tumor-Centered
      Approach: Challenges, Opportunities, and Highlights from the Development of
      TLD1433.
AB  - Transition metal complexes are of increasing interest as photosensitizers in
      photodynamic therapy (PDT) and, more recently, for photochemotherapy (PCT). In
      recent years, Ru(II) polypyridyl complexes have emerged as promising systems for
      both PDT and PCT. Their rich photochemical and photophysical properties derive
      from a variety of excited-state electronic configurations accessible with visible
      and near-infrared light, and these properties can be exploited for both energy-
      and electron-transfer processes that can yield highly potent oxygen-dependent
      and/or oxygen-independent photobiological activity. Selected examples highlight
      the use of rational design in coordination chemistry to control the lowest-energy
      triplet excited-state configurations for eliciting a particular type of
      photoreactivity for PDT and/or PCT effects. These principles are also discussed
      in the context of the development of TLD1433, the first Ru(II)-based
      photosensitizer for PDT to enter a human clinical trial. The design of TLD1433
      arose from a tumor-centered approach, as part of a complete PDT package that
      includes the light component and the protocol for treating non-muscle invasive
      bladder cancer. Briefly, this review summarizes the challenges to bringing PDT
      into mainstream cancer therapy. It considers the chemical and photophysical
      solutions that transition metal complexes offer, and it puts into context the
      multidisciplinary effort needed to bring a new drug to clinical trial.

PMID- 30295468
TI  - N-type Bi-doped SnSe Thermoelectric Nanomaterials Synthesized by a Facile
      Solution Method.
AB  - An n-type Bi-doped SnSe was synthesized by a facile solution method followed by
      spark plasma sintering. We used bismuth(III) 2-ethyhexanoate as a cationic dopant
      precursor, which can absorb on the powder surface and then diffuse into the
      lattice to realize the substitution of Sn by Bi. A strip structure with low-angle
      boundary was constructed for effective phonon scattering. With increasing content
      of Bi, the carrier concentration decreased from 1.35 * 1019 cm-3 (p-type) in
      undoped SnSe to 4.7 * 1014 cm-3 (n-type) in Sn0.99Bi0.01Se and then increased to
      1.3 * 1015 cm-3 (n-type) in Sn0.97Bi0.03Se. The Seebeck coefficient changed from
      positive to negative and presented n-type conducting behavior in the whole
      measured temperature range from 300 to 773 K, reaching a maximum absolute value
      of ~900 MUV K-1 at room temperature and ~300 MUV K-1 at 773 K. Considering the
      rich variety of metal 2-ethylhexanoates, higher thermoelectric performance is
      expected by different cationic doping in solution-synthesized nanomaterials.

PMID- 30295469
TI  - Horizontal and Vertical Distribution of Microplastics in Korean Coastal Waters.
AB  - This is the first survey to investigate the vertical distribution and composition
      of microplastics >20 MUm at the surface (0-0.2 m; bulk sample) and in the water
      column (3-58 m depth; pump) of six semi-enclosed bays and two nearshore areas of
      South Korea. The average microplastic abundance of 41 stations at all sampling
      depths was 871 particles/m3, and the microplastic abundance near urban areas
      (1051 particles/m3) was significantly higher than that near rural areas (560
      particles/m3). Although the average microplastic abundances in the midcolumn (423
      particles/m3) and bottom water (394 particles/m3) were approximately 4 times
      lower than that of surface water (1736 particles/m3), microplastics prevailed
      throughout the water column in concentrations of 10-2000 particles/m3. The
      average sizes of fragment and fiber type microplastics were 197 and 752 MUm,
      respectively. Although the polymer composition differed by depth depending on the
      particle size and density, polypropylene and polyethylene predominated throughout
      the water column regardless of their low density and particle size. Finally, the
      middle and bottom water samples contained higher abundances of microplastics than
      predicted by a model based on physical mixing, indicating that biological
      interactions also influence the downward movement of low-density microplastics.

PMID- 30295470
TI  - Mechanical-Tunable Capillary-Force-Driven Self-Assembled Hierarchical Structures
      on Soft Substrate.
AB  - Capillary-force-driven self-assembly (CFSA) has been combined with many top-down
      fabrication methods to be alternatives to conventional single micro/nano
      manufacturing techniques for constructing complicated micro/nanostructures.
      However, most CFSA structures are fabricated on a rigid substrate, and little
      attention is paid to the tuning of CFSA, which means that the pattern of
      structures cannot be regulated once they are manufactured. Here, by combining
      femtosecond laser direct writing with CFSA, a flexible method is proposed to
      fabricate self-assembled hierarchical structures on a soft substrate. Then, the
      tuning of the self-assembly process is realized with a mechanical-stretching
      strategy. With this method, different patterns of tunable self-assembled
      structures are obtained before tuning and after release, which is difficult to
      achieve with other techniques. In addition, as a proof-of-concept application,
      this mechanical tunable self-assembly of microstructures on a soft substrate is
      used for smart displays and versatile micro-object trapping.

PMID- 30295471
TI  - Polybrominated Diphenyl Ethers Quinone Induced Parthanatos-like Cell Death
      through a Reactive Oxygen Species-Associated Poly(ADP-ribose) Polymerase 1
      Signaling.
AB  - Polybrominated diphenyl ethers (PBDEs) are emerging organic environmental
      pollutants, which were accused of various toxic effects. Here, we studied the
      role of a potential PBDEs quinone metabolite, PBDEQ, on cytotoxicity, oxidative
      DNA damage, and the alterations of signal cascade in HeLa cells. PBDEQ exposure
      leads to reactive oxygen species (ROS) accumulation, mitochondrial membrane
      potential (MMP) loss, lactate dehydrogenase (LDH) release, increasing terminal
      transferase-mediated dUTP-biotin nick end labeling (TUNEL) positive foci, and the
      elevation of apoptosis rate. Furthermore, we showed PBDEQ exposure result in
      increased DNA migration, micronucleus frequency, and the promotion of 8-OHdG and
      phosphorylation of histone H2AX (gamma-H2AX) levels. Mechanism study indicated
      that PBDEQ caused poly(ADP-ribose) polymerase 1 (PARP-1) activation and apoptosis
      inducing factor (AIF) nuclear translocation. All together, these results
      confirmed the occurrence of parthanatos-like cell death upon PBDEQ exposure.

PMID- 30295472
TI  - Site-Selective Cross-Coupling of Remote Chlorides Enabled by Electrostatically
      Directed Palladium Catalysis.
AB  - Control of site-selectivity in chemical reactions that occur remote from existing
      functionality remains a major challenge in synthetic chemistry. We describe a
      strategy that enables three of the most commonly used cross-coupling processes to
      occur with high site-selectivity on dichloroarenes that bear acidic functional
      groups. We have achieved this by repurposing an established sulfonylated
      phosphine ligand to exploit its inherent bifunctionality. Mechanistic studies
      suggest that the sulfonate group engages in attractive electrostatic interactions
      with the cation associated with the deprotonated substrate, guiding cross
      coupling to the chloride at the arene meta position. This counterintuitive
      combination of anionic ligand and anionic substrate demonstrates an alternative
      design principle when considering the application of noncovalent interactions to
      direct catalysis.

PMID- 30295473
TI  - Hybrid Metal-Organic-Framework/Inorganic Nanocatalyst toward Highly Efficient
      Discoloration of Organic Dyes in Aqueous Medium.
AB  - Nanoscale metal-organic frameworks (NMOFs) represent a unique class of solids
      with superior adsorption, mass transport, and catalytic properties. In this
      study, a facile and novel approach was developed for the generation of hybrid Cu
      NMOF/Ce-doped-Mg-Al-LDH nanocatalyst through in situ self-assembly and
      solvothermal synthesis of a 2D Cu-NMOF, [Cu2(MU-OH)(MU4-btc)(phen)2] n.5 nH2O
      {H3btc, trimesic acid; phen, 1,10-phenanthroline}, on a cerium-doped Mg-Al
      layered double hydroxide (Ce-doped-Mg-Al-LDH) matrix. Self-assembly between Cu
      NMOF nanocrystals and exfoliated LDH led to their nanoscale mixing and prevented
      the formation of aggregated Cu-NMOF nanoparticles. In the resulting hybrid
      nanostructure, Cu-NMOF nanocrystals (~10-20 nm particle size) are anchored
      uniformly on a Ce-doped-Mg-Al-LDH's surface, possessing a dimension of several
      hundred nanometers. Catalytic activity of Cu-NMOF/Ce-doped-Mg-Al-LDH and Cu-NMOF
      was evaluated under ambient conditions in the reductive degradation
      (discoloration) of aqueous solutions of 4-nitrophenol (4-NP, model substrate) and
      a series of commercial organic dyes by applying sodium borohydride as a reducing
      agent. The Cu-NMOF/Ce-doped-Mg-Al-LDH nanocatalyst exhibited an outstanding
      catalytic activity toward degradation of 4-NP, with kapp (rate constant) of 0.03
      and a catalyst TOF (turnover frequency) up to 7.1 * 103 h-1. Full and very quick
      discoloration of organic dyes {rhodamine B (RhB), methylene blue (MB), Congo red
      (CR), methyl orange (MO), and rhodamine 6G (R6G)} was also achieved with TOF
      values of up to 1.4 * 105/h. A superior activity of the hybrid nanocatalyst over
      Cu-NMOF can be regarded as a synergic effect among Cu-NMOF and Ce-doped-Mg-Al-LDH
      components, while the Ce-doped-Mg-Al-LDH carrier acts as a cocatalyst. The hybrid
      nanocatalyst can easily be recovered and reused successfully for the five
      consecutive reaction runs with the same catalytic performance. This study also
      shows that NMOFs can be easily incorporated onto conventional catalyst supports,
      resulting in hybrid nanocatalysts with a highly uniform structural architecture,
      controlled chemical composition, and excellent catalytic function.

PMID- 30295475
TI  - Atmospheric Solid Analysis Probe and Modified Desorption Electrospray Ionization
      Mass Spectrometry for Rapid Screening and Semi-Quantification of Zilpaterol in
      Urine and Tissues of Sheep.
AB  - Ambient ionization mass spectrometric methods including desorption electrospray
      ionization (DESI) and atmospheric solid analysis probe (ASAP) have great
      potential for applications requiring real-time screening of target molecules in
      complex matrixes. Such techniques can also rapidly produce repeatable
      semiquantitative data, with minimal sample preparation, relative to liquid
      chromatography-mass spectrometry (LC-MS). In this study, a commercial ASAP probe
      was used to conduct both ASAP-MS and modified DESI (MDESI) MS analyses. We
      conducted real-time qualitative and semiquantitative analysis of the leanness
      enhancing agent zilpaterol in incurred sheep urine, kidney, muscle, liver, and
      lung samples using ASAP-MS and MDESI MS. Using ASAP, limits of detection (LOD)
      and quantitation (LOQ) in urine were 1.1 and 3.7 ng/mL, respectively, while for
      MDESI MS they were 1.3 and 4.4 ng/mL, respectively. The LODs for tissues were 0.1
      0.4 ng/g using ASAP, and 0.2-0.6 ng/g with MDESI MS. The LOQs of the tissues in
      ASAP were 0.4-1.2 ng/g and 0.5-2.1 ng/g in MDESI MS. Trace levels of zilpaterol
      were accurately analyzed in urine and tissues of sheep treated with dietary
      zilpaterol HCl. The correlation coefficient ( R2) between semiquantitative ASAP
      MS and MDESI MS results of urine samples was 0.872. The data from ASAP and MDESI
      MS were validated using LC-MS/MS; urinary zilpaterol concentrations >=5.0 ng/mL
      or tissue zilpaterol concentrations >=1.5 ng/g were detected by ASAP and MDESI
      MS, respectively, 100% of the time. Forty samples could be analyzed in
      triplicate, directly from biological matrixes in under an hour.

PMID- 30295474
TI  - Mechanistic Insight on the Formation of GaN:ZnO Solid Solution from Zn-Ga Layered
      Double Hydroxide Using Urea as the Nitriding Agent.
AB  - A solid solution of GaN and ZnO (GaN:ZnO) is promising as a photocatalyst for
      visible-light-driven overall water splitting to produce H2. However, several
      obstacles still exist in the conventional preparation procedure of GaN:ZnO. For
      example, the atomic distributions of Zn and Ga are nonuniform in GaN:ZnO when a
      mixture of the metal oxides, i.e. Ga2O3 and ZnO, is used as a precursor. In
      addition, GaN:ZnO is generally prepared under a harmful NH3 flow for long
      durations at high temperatures. Here, a facile synthesis of GaN:ZnO with
      homogeneous atomic composition via a simple and safe procedure is reported. A
      layered double hydroxide (LDH) containing Zn2+ and Ga3+ was used to increase the
      uniformity of the atomic distributions of Zn and Ga in GaN:ZnO. We employed urea
      as a nitriding agent instead of gaseous NH3 to increase the safety of the
      reaction. Through the optimization of reaction conditions such as heat treatment
      temperature and content of urea, single-phase GaN:ZnO was successfully obtained.
      In addition, the nitridation mechanism using urea was investigated in detail. NH3
      released from the thermal decomposition of urea did not directly nitride the LDH
      precursor. X-ray absorption and infrared  spectroscopies revealed that Zn(CN2)
      like intermediate species were generated at the middle temperature range and Ga-N
      bonds formed at high temperature along with dissociation of CO and CO2.

PMID- 30295477
TI  - Nitro-Group-Containing Drugs.
AB  - The nitro group is considered to be a versatile and unique functional group in
      medicinal chemistry. Despite a long history of use in therapeutics, the nitro
      group has toxicity issues and is often categorized as a structural alert or a
      toxicophore, and evidence related to drugs containing nitro groups is rather
      contradictory. In general, drugs containing nitro groups have been extensively
      associated with mutagenicity and genotoxicity. In this context, efforts toward
      the structure-mutagenicity or structure-genotoxicity relationships have been
      undertaken. The current Perspective covers various aspects of agents that contain
      nitro groups, their bioreductive activation mechanisms, their toxicities, and
      approaches to combat their toxicity issues. In addition, recent advances in the
      field of anticancer, antitubercular and antiparasitic agents containing nitro
      groups, along with a patent survey on hypoxia-activated prodrugs containing nitro
      groups, are also covered.

PMID- 30295476
TI  - Mechanism of Permanganate-Promoted Dihydroxylation of Complex Diketopiperazines:
      Critical Roles of Counter-cation and Ion-Pairing.
AB  - The mechanism of permanganate-mediated dual C-H oxidation of complex
      diketopiperazines has been examined with density functional theory computations.
      The products of these oxidations are enabling intermediates in the synthesis of
      structurally diverse ETP natural products. We evaluated, for the first time, the
      impact of ion-pairing and aggregation states of the permanganate ion and counter
      cations, such as bis(pyridine)-silver(I) (Ag+) and tetra- n-butylammonium (TBA+),
      on the C-H oxidation mechanism. The C-H abstraction occurs through an open shell
      singlet species, as noted previously, followed by O-rebound and a competing OH
      rebound pathway. The second C-H oxidation proceeds with a second equivalent of
      oxidant with lower free energy barriers than the first C-H oxidation due to
      directing effects and the generation of a more reactive oxidant species after the
      first C-H oxidation. The success and efficiency of the second C-H oxidation are
      found to be critically dependent on the presence of an ion-paired oxidant. We
      used the developed mechanistic knowledge to rationalize an experimentally
      observed oxidation pattern for C3-indole-substituted diketopiperazine (+)-5 under
      optimal oxidation conditions: namely, the formation of diol (-)-6 as a single
      diastereomer and lack of the ketone products. We proposed two factors that may
      impede the ketone formation: (i) the conformational flexibility of the
      diketopiperazine ring, and (ii) hindrance of this site, making it less accessible
      to the ion-paired oxidant species.

PMID- 30295478
TI  - A Method for Synthesis of 3-Hydroxy-1-indanones via Cu-Catalyzed Intramolecular
      Annulation Reactions.
AB  - We report a facile and highly efficient method that copper-catalyzed
      intramolecular annulation to synthesize 3-hydroxy-1-indanones employing simple 2
      ethynylbenzaldehyde as starting materials was achieved successfully. This
      protocol provided a simple synthetic approach to afford 3-hydroxy-1-indanones
      under mild conditions in good to excellent yields.

PMID- 30295479
TI  - On-Water Synthesis of 2-Substituted Quinolines from 2-Aminochalcones Using
      Benzylamine as the Nucleophilic Catalyst.
AB  - On-water synthesis of 2-substituted quinolines from 2-aminochalcone derivatives
      was developed using benzylamine as the nucleophilic catalyst. Various 2
      aminochalcones could be applied to this protocol, and the desired 2-substituted
      quinoline products were isolated in excellent yields by simple filtration.
      Furthermore, we elucidated the role of benzylamine in this transformation and
      provided the detailed reaction mechanism. This protocol has several additional
      advantages, such as simple operation, broad substrate scope, good functional
      group tolerance, easy product isolation, recycling of the catalyst, and gram
      scale synthesis.

PMID- 30295480
TI  - Isolation of Tryptanthrin and Reassessment of Evidence for Its Isobaric Isostere
      Wrightiadione in Plants of the Wrightia Genus.
AB  - A series of Wrightia hanleyi extracts was screened for activity against
      Mycobacterium tuberculosis H37Rv. One active fraction contained a compound that
      initially appeared to be either the isoflavonoid wrightiadione or the alkaloid
      tryptanthrin, both of which have been previously reported in other Wrightia
      species. Characterization by NMR and MS, as well as evaluation of the literature
      describing these compounds, led to the conclusion that wrightiadione (1) was
      misidentified in the first report of its isolation from W. tomentosa in 1992 and
      again in 2015 when reported in W. pubescens and W. religiosa. Instead, the
      molecule described in these reports and in the present work is almost certainly
      the isobaric (same nominal mass) and isosteric (same number of atoms, valency,
      and shape) tryptanthrin (2), a well-known quinazolinone alkaloid found in a
      variety of plants including Wrightia species. Tryptanthrin (2) is also accessible
      synthetically via several routes and has been thoroughly characterized.
      Wrightiadione (1) has been synthesized and characterized and may have useful
      biological activity; however, this compound can no longer be said to be known to
      exist in Nature. To our knowledge, this misidentification of wrightiadione (1)
      has heretofore been unrecognized.

PMID- 30295481
TI  - Auranthine, a Benzodiazepinone from Penicillium aurantiogriseum: Refined
      Structure, Absolute Configuration, and Cytotoxicity.
AB  - The structure of the known Penicillium aurantiogriseum-derived secondary
      metabolite auranthine was refined using a combination of synthetic,
      spectroscopic, and X-ray diffractometric approaches. Thus, auranthine was shown
      to be a fused quinazolino benzodiazepinedione (2) bearing an acyclic aliphatic
      nitrile moiety, thereby significantly differing from the originally proposed
      structure 1 published in 1986. Its absolute configuration was confirmed by CD
      spectroscopy and DFT calculations. The cultivation of P. aurantiogriseum was
      optimized, allowing high production of auranthine. The cytotoxicity profile of
      auranthine and its semisynthetic analogues is reported. The refined structure of
      auranthine provides a valid target for the total synthesis of this underexplored
      natural product and its derivatives.

PMID- 30295482
TI  - Kaempferol Binding to Zinc(II), Efficient Radical Scavenging through Increased
      Phenol Acidity.
AB  - Zinc(II) enhances radical scavenging of the flavonoid kaempferol (Kaem) most
      significantly for the 1:1 Zn(II)-Kaem complex in equilibrium with the 1:2 Zn(II)
      Kaem complex both with high affinity at 3-hydroxyl and 4-carboxyl coordination.
      In methanol/chloroform (7/3, v/v), 1:1 Zn(II)-Kaem complex reduces beta-carotene
      radical cation, beta-Car*+, with a second-order rate constant, 1.88 * 108 L.mol
      1.s-1, while both Kaem and 1:2 Zn(II)-Kaem complex are nonreactive, as determined
      by laser flash photolysis. In ethanol, 1:1 Zn(II)-Kaem complex reduces the 2,2
      diphenyl-1-picrylhydrazyl radical, DPPH*, with a second-order rate constant, 2.48
      * 104 L.mol-1.s-1, 16 times and 2 times as efficient as Kaem and 1:2 Zn(II)-Kaem
      complex, respectively, as determined by stopped-flow spectroscopy. Density
      functional theory calculation results indicate significantly increased acidity of
      Kaem as ligand in 1:1 Zn(II)-Kaem complex other than in 1:2 Zn(II)-Kaem complex.
      Kaem in 1:1 Zn(II)-Kaem complex loses two protons (one from 3-hydroxyl and one
      from phenolic hydroxyl) forming 1:1 Zn(II)-(Kaem-2H) during binding with Zn(II),
      while Kaem in 1:2 Zn(II)-Kaem complex loses one proton in each ligand forming
      Zn(II)-(Kaem-H)2, as confirmed by UV-vis absorption spectroscopy. Zn(II)-(Kaem
      2H) is a far stronger reductant than Kaem and Zn(II)-(Kaem-H)2 as determined by
      cyclic voltammetry. Significant rate increases for the 1:1 complex in both beta
      Car*+ scavenging by electron transfer and DPPH* scavenging by hydrogen atom
      transfer were ascribed to decreases of ionization potential and of bond
      dissociation energy of 4'-OH for deprotonated Zn(II)-(Kaem-2H), respectively.
      Increased phenol acidity of plant polyphenols by 1:1 coordination with Zn(II) may
      explain the unique function of Zn(II) as a biological antioxidant and may help to
      design nontoxic metal-based drugs derived from natural bioactive molecules.

PMID- 30295483
TI  - Phospholipid-Cellulose Interactions: Insight from Atomistic Computer Simulations
      for Understanding the Impact of Cellulose-Based Materials on Plasma Membranes.
AB  - Cellulose is an important biocompatible and nontoxic polymer widely used in
      numerous biomedical applications. The impact of cellulose-based materials on
      cells and, more specifically, on plasma membranes that surround cells, however,
      remains poorly understood. To this end, here, we performed atomic-scale molecular
      dynamics simulations of phosphatidylcholine (PC) and phosphatidylethanolamine
      (PE) bilayers interacting with the surface of a cellulose crystal. Both biased
      umbrella sampling and unbiased simulations clearly show the existence of strong
      attractive interactions between phospholipids and cellulose: the free energy of
      the cellulose-bilayer binding was found to be -1.89 and -1.96 kJ/mol per
      cellulose dimer for PC and PE bilayers, respectively. Although the values are
      similar, there is a pronounced difference between PC and PE bilayers. The driving
      force in both cases is the formation of hydrogen bonds. There are two distinct
      types of hydrogen bonds: (1) between the lipid head groups and the hydroxyl
      (hydroxymethyl) groups of cellulose, and (2) lipid-water and cellulose-water
      bonds. The former is the dominant component for PE systems whereas the latter
      dominates in PC systems. This suggests that achieving controlled binding via new
      cellulose modifications must pay close attention to the lipid head groups
      involved. The observed attractive phospholipid-cellulose interactions have a
      significant effect on bilayer properties: a cellulose crystal induces noticeable
      structural perturbations on the bilayer leaflet next to the crystal. Given that
      such perturbations can be undesirable when it comes to the interactions of
      cellulose-based materials with cell membranes, our computational studies suggest
      that the impact of cellulose could be reduced through chemical modification of
      the cellulose surface which prevents cellulose-phospholipid hydrogen bonding.

PMID- 30295484
TI  - Synthesis of Functionalized Indoles via Palladium-Catalyzed Aerobic
      Cycloisomerization of o-Allylanilines Using Organic Redox Cocatalyst.
AB  - A scalable and practical synthesis of functionalized indoles via Pd- tBuONO
      cocatalyzed aerobic cycloisomerization of o-allylanilines is reported. Using
      molecular oxygen as a terminal oxidant, a series of substituted indoles were
      prepared in moderate to good yields. The avoidance of hazardous oxidants, heavy
      metal cocatalysts, and high boiling point solvents such as DMF and DMSO enables
      this method to be applied in pharmaceutical synthesis. A practical gram-scale
      synthesis of indomethacin demonstrates its application potential.

PMID- 30295486
TI  - Direct Experimental Characterization of Contributions from Self-Motion of
      Hydrogen and from Interatomic Motion of Heavy Atoms to Protein Anharmonicity.
AB  - One fundamental challenge in biophysics is to understand the connection between
      protein dynamics and its function. Part of the difficulty arises from the fact
      that proteins often present local atomic motions and collective dynamics on the
      same time scales, and challenge the experimental identification and
      quantification of different dynamic modes. Here, by taking lyophilized proteins
      as the example, we combined deuteration technique and neutron scattering to
      separate and characterize the self-motion of hydrogen and the collective
      interatomic motion of heavy atoms (C, O, N) in proteins on the pico-to-nanosecond
      time scales. We found that hydrogen atoms present an instrument-resolution
      dependent onset for anharmonic motions, which can be ascribed to the thermal
      activation of local side-group motions. However, the protein heavy atoms exhibit
      an instrument-resolution-independent anharmonicity around 200 K, which results
      from unfreezing of the relaxation of the protein structures on the laboratory
      equilibrium time (100-1000 s), softening of the entire bio-macromolecules.

PMID- 30295485
TI  - UV-Vis, Fluorescence, and Resonance Raman Spectroscopic and Density Functional
      Theoretical Studies on 3-Amino-1,2,4-triazole: Microsolvation and Solvent
      Dependent Nonadiabatic Excited State Decay in Solution.
AB  - The microsolvation and photophysics of 3-amino-1,2,4-triazole (3AT) after
      excitation to the light-absorbing S2(npi*) state were studied by using resonance
      Raman spectroscopy and single component artificial force-induced reaction (SC
      AFIR) in a global reaction route mapping (GRRM) strategy. The vibrational spectra
      were assigned on the basis of experimental data and density functional theory
      (DFT) calculations. The resonance Raman spectra of 3AT were measured to probe the
      excited state structural dynamics in the Franck-Condon region. The conformations
      of 3AT(CH3CN)1, 3AT(CH3OH)2, and 3AT(H2O)2 clusters were determined by combining
      vibrational spectrum experiments and B3LYP/6-311++G(d,p) computations. DFT
      calculations were carried out to obtain the minimal excitation energies of the
      lower-lying singlet excited states, and the curve-crossing points. It was
      revealed that the short-time structural dynamics of 3AT were dominated by the N-N
      stretching coordinates. An excited state decay mechanism is proposed: 3AT is
      initially excited to the S2(npi*) state, then the conical intersection (CI) of
      the S2(npi*)/S1(pipi*) potential energy surfaces is crossed, and 3AT then decays
      to the lower solvent-dependent excited state S1(pipi*). It subsequently returns
      to the S0 state, accompanied by a large Stokes fluorescence shift, which was
      interpreted as the stabilized S1(pipi*) excited state bonding to several water
      molecules via intermolecular hydrogen bonding.

PMID- 30295487
TI  - Ligand-Based Fluorine NMR Screening: Principles and Applications in Drug
      Discovery Projects.
AB  - Ligand-based fluorine NMR screening has gained popularity in drug discovery
      projects during the past decade and has become a powerful methodology to produce
      high quality hits. Its high sensitivity to protein binding makes it particularly
      suitable for fragment screening, allowing detection and binding strength
      measurement of very weak affinity ligands. The screening can be performed in
      direct or competition format, and its versatility allows application to complex
      biological and chemical systems. As the potential of the methodology has now been
      recognized and successfully demonstrated in several relevant medicinal chemistry
      projects, it is now an appropriate time to report the learned lessons and point
      the way to the future. In this Perspective the principles of the methodology
      along with several applications to pharmaceutical projects are presented.

PMID- 30295489
TI  - Stereoselective Protection-Free Asymmetric Total Synthesis of (+)-Chamuvarinin, a
      Potent Anticancer and Antitrypanosomal Agent: Substrate-Controlled Construction
      of the Adjacently Linked Oxatricyclic Core by Internal Alkylation.
AB  - A stereoselective protection-free asymmetric total synthesis of (+)-chamuvarinin
      (1), a potent anticancer and antitrypanosomal agent, has been accomplished. The
      adjacently linked [bis(tetrahydrofuran)]tetrahydropyran (THF-THF-THP) core of
      this natural product with seven stereogenic centers was constructed in a
      completely substrate-controlled fashion. The inter-ring stereochemistry (
      threo,threo,threo) of the oxatricyclic core was established in a stereoselective
      fashion by a chelation-controlled Keck allylation, whereas the intraring cis or
      trans relative stereochemistry was controlled by a stereoselective internal
      alkylation.

PMID- 30295490
TI  - Incorporating In-Source Fragment Information Improves Metabolite Identification
      Accuracy in Untargeted LC-MS Data Sets.
AB  - In-source fragmentation occurs as a byproduct of electrospray ionization. We find
      that ions produced as a result of in-source fragmentation often match fragment
      ions produced during MS/MS fragmentation, and we take advantage of this
      phenomenon in a novel algorithm to analyze LC-MS metabolomics data sets. Our
      approach organizes coeluting MS1 features into a single peak group and then
      identifies in-source fragments among coeluting features using MS/MS spectral
      libraries. We tested our approach using previously published data of verified
      metabolites and compared the results to features detected by other mainstream
      metabolomics tools. Our results indicate that considering in-source fragment
      information as a part of the identification process increases the annotation
      quality, allowing us to leverage MS/MS data in spectrum libraries even if MS/MS
      scans were not collected.

PMID- 30295491
TI  - "Trojan Horse" DNA Nanostructure for Personalized Theranostics: Can It Knock on
      the Door of Preclinical Practice?
AB  - Nanotheranostics, combing diagnostic and therapeutic components in an all-in-one
      nanomaterial, possess exciting potentials for precision nanomedicine. However, a
      major obstacle for current nanotheranostics to enter preclinical and/or clinical
      trials is the intrinsic toxicities of these nanomaterials. As an emerging
      biomaterial, the bioinspired DNA nanostructure shows advantages for constructing
      better nanotheranostics due to its excellent features, including native
      biocompatibility, full programmability, and ready accessibility. In this feature
      article, we highlight recent advances in the design of DNA-nanostructure-based
      diagnostics and/or therapeutics capable of specifically responding to biological
      stimuli in a dynamic way, with a particular focus on the design mechanism,
      responsive performance, and potential for preclinical and/or clinical trials in
      personalized theranostics.

PMID- 30295488
TI  - Chemical Exchange Reaction Effect on Polarization Transfer Efficiency in SLIC
      SABRE.
AB  - Signal Amplification By Reversible Exchange (SABRE) is a new and rapidly
      developing hyperpolarization technique. The recent discovery of Spin-Lock Induced
      Crossing SABRE (SLIC-SABRE) showed that high field hyperpolarization transfer
      techniques developed so far were optimized for singlet spin order that does not
      coincide with the experimentally produced spin state. Here, we investigated the
      SLIC-SABRE approach and the most advanced quantitative theoretical SABRE model to
      date. Our goal is to achieve the highest possible polarization with SLIC-SABRE at
      high field using the standard SABRE system, IrIMes catalyst with pyridine. We
      demonstrated the accuracy of the SABRE model describing the effects of various
      physical parameters such as the amplitude and frequency of the radio frequency
      field, and the effects of chemical parameters such as the exchange rate
      constants. By fitting the model to the experimental data, the effective life time
      of the SABRE complex was estimated, as well as the entropy and enthalpy of the
      complex-dissociation reaction. We show, for the first time, that this SLIC-SABRE
      model can be useful for the evaluation of the chemical exchange parameters that
      are very important for the production of highly polarized contrast agents via
      SABRE.

PMID- 30295492
TI  - Divergent Reactivity in Pd-Catalyzed [3,3]-Sigmatropic Rearrangement of Allyloxy-
      and Propargyloxyindoles Revealed by Computation and Experiment.
AB  - Detailed computational (DFT) studies of the palladium(II)-catalyzed Claisen
      rearrangement of 2-allyloxy- and propargyloxyindoles revealed an unexpected
      divergent mode of reactivity. Subsequent experimental kinetic isotope effects are
      in accord with the mechanism derived from the computations. The computational
      results led to the development of Pd(II)-catalyzed [3,3]-sigmatropic
      rearrangement of 3-aryl substituted 2-propargylindoles.

PMID- 30295493
TI  - Cyclization Reaction of Donor-Acceptor Oxiranes with N,N'-Disubstituted
      Thioureas: A Domino Process to trans-Dihydropyrimidines.
AB  - An unprecedented cyclization reaction of donor-acceptor oxiranes with N,N'
      disubstituted thioureas to construct trans-dihydropyrimidines is presented.
      Preliminary reaction mechanism studies demonstrated that the reaction underwent
      sequential cycloaddition/amine ester exchange/oxygen-sulfur
      exchange/desulfuration/Michael addition process. A wide range of trans
      dihydropyrimidines were produced with high yields up to 94% by using this method.

PMID- 30295494
TI  - Iron-Catalyzed Enantioselective Si-H Bond Insertions.
AB  - The first iron-catalyzed enantioselective Si-H bond insertion reaction of alpha
      diazoesters was developed. A new chiral spiro-bisoxazoline ligand has proven to
      be an optimal ligand for the asymmetric reaction to give versatile chiral alpha
      silyl esters in good yields with high enantioselectivities. The mechanism and
      detailed stereochemical models for enantioselective induction were elucidated by
      DFT calculations, suggesting that the reaction proceeds via a concerted quintet
      transition state.

PMID- 30295495
TI  - Transition Metal-Free Cross-Dehydrogenative Coupling Reaction of Coumarins with
      Acetonitrile or Acetone.
AB  - A transition metal-free cross-dehydrogenative coupling of coumarins with
      acetonitrile or acetone has been established. A series of coumarins were
      subjected to reaction with acetonitrile or acetone in the presence of tert-butyl
      benzoperoxoate and potassium fluoride for direct synthesis of 3-cyanomethyl (or
      acetomethyl) coumarins. The method exhibits good functional group tolerance, and
      desired products were obtained in moderate to good yields. Meanwhile, a radical
      pathway was proposed to describe the cross-dehydrogenative coupling of coumarins
      with acetonitrile.

PMID- 30295496
TI  - Synthesis of Two-Photon Active Tricomponent Fluorescent Probe for Distinguishment
      of Biotin Receptor Positive and Negative Cells and Imaging 3D-Spheroid.
AB  - A fluorescence microscopy-based distinguishment between biotin receptor (BiR)
      positive and negative cell lines via receptor-mediated endocytosis has been
      demonstrated. A water-soluble, three-component, two-photon (2P) active
      solvatofluorochromic probe has been designed and synthesized. The applicability
      of the probe for 2P microscopy and 3D-spheroid was also assessed.

PMID- 30295497
TI  - Synthesis and Characterization of Anguibactin To Reveal Its Competence To
      Function as a Thermally Stable Surrogate Siderophore for a Gram-Negative
      Pathogen, Acinetobacter baumannii.
AB  - Total synthesis of anguibactin was accomplished for the first time, and the
      following biochemical characterizations allowed for the determination of its
      Fe(III) binding mode as well as the demonstration of its iron delivery capability
      for Acinetobacter baumannii. These properties, in addition to the thermal
      stability over acinetobactin, render anguibactin as a competent surrogate
      siderophore that can be useful for the future development of a siderophore-based
      antibiotic delivery system against A. baumannii.

PMID- 30295498
TI  - Synthesis and Application of Perylene-Embedded Benzoazoles for Small-Molecule
      Organic Solar Cells.
AB  - Two new building blocks of perylene-embedded benzoazoles containing both rigid 2D
      conjugated aromatic rings and flexible branched alkyl chains were designed and
      facilely synthesized in high yields for organic solar cells (OSCs). With a
      typical acceptor of diketopyrrolopyrrole, small molecular OSC donors constructed
      in an acceptor-fused donor-acceptor motif exhibit excellent solubility,
      stability, and light absorption with tunable frontier orbitals, leading to a
      power conversion efficiency of up to 2.88% in preliminary OSCs.

PMID- 30295499
TI  - Creation of Magnetic Skyrmion Bubble Lattices by Ultrafast Laser in Ultrathin
      Films.
AB  - Magnetic skyrmions are topologically nontrivial spin textures which hold great
      promise as stable information carriers in spintronic devices at the nanoscale.
      One of the major challenges for developing novel skyrmion-based memory and logic
      devices is fast and controlled creation of magnetic skyrmions at ambient
      conditions. Here we demonstrate controlled generation of skyrmion bubbles and
      skyrmion bubble lattices from a ferromagnetic state in sputtered ultrathin
      magnetic films at room temperature by a single ultrafast (35 fs) laser pulse. The
      skyrmion bubble density increases with the laser fluence, and it finally becomes
      saturated, forming disordered hexagonal lattices. Moreover, we present that the
      skyrmion bubble lattice configuration leads to enhanced topological stability as
      compared to isolated skyrmions, suggesting its promising use in data storage. Our
      findings shed light on the optical approach to the skyrmion bubble lattice in
      commonly accessible materials, paving the road toward the emerging skyrmion-based
      memory and synaptic devices.

PMID- 30295500
TI  - Analysis of Adsorbed Layers of Benzyldimethyldodecylammonium Bromide on Silica
      Particles in Water Using the Sorbent Mass Variation Method.
AB  - A "sorbent mass variation" (SMV) method has been suggested to investigate the
      adsorption at solid-liquid interfaces, which can provide information on the
      adsorbed layer structure including its thickness and composition. However, there
      has been little research focused on the method, and therefore, it is essential to
      examine its general applicability. Herein, the adsorption of
      benzyldimethyldodecylammonium bromide (BDDABr), a cationic surfactant, on silica
      (SiO2) nanoparticles (with ~12 and 24 nm in size, denoted as S-SiO2 and L-SiO2,
      respectively) in water was investigated using the SMV method. The adsorption
      isotherms all show a linearly declining tendency in the saturated adsorption
      regime, consistent with the prediction of the SMV model. The adsorption is
      interpreted to form noncomplete bilayers (or isolated admicelles). The
      thicknesses of the adsorbed bilayers on S-SiO2 and L-SiO2 are estimated to be
      ~2.9 and 2.7 nm, respectively, and the volume fractions of BDDABr in the
      saturated adsorbed layers are 0.63 and 0.68, respectively. In addition, the
      change in the Gibbs free energy of the adsorption process is also analyzed,
      showing its spontaneous nature. This work demonstrates that the SMV method is
      available for investigation on the adsorption of surfactants at solid-liquid
      interfaces, which can provide information on the structure and formation
      thermodynamics of adsorbed layers.

PMID- 30295501
TI  - Clinical significance of antibodies to antigens in the Raph, John Milton Hagen,
      I, Globoside, Gill, Rh-associated glycoprotein, FORS, JR, LAN, Vel, CD59, and
      Augustine blood group systems.
AB  - CONCLUSIONS: This article reviews information on the clinical significance of
      antibodies to antigens in the Raph, John Milton Hagen, I, Globoside, Gill, Rh
      associated glycoprotein, FORS, JR, LAN, Vel, CD59, and Augustine blood group
      systems. Antibodies to many of the antigens in these groups are rarely
      encountered because of the high prevalence of the associated antigens in most
      populations. For many of these antibodies, the clinical significance-that is, the
      potential to cause reduced survival of transfused antigen-positive red blood
      cells or a transfusion reaction (e.g., anti-P, anti-Jra, and anti-Lan), and/or
      hemolytic disease of the fetus and newborn (e.g., anti-RHAG4 and anti-Vel)-has
      been documented. For other antibodies, their prevalence is so rare that
      information on the clinical significance of their antibodies is not available
      (e.g., anti-FORS1).

PMID- 30295502
TI  - Rouleaux and saline replacement.
AB  - CONCLUSIONS: Rouleaux is a phenomenon that commonly occurs in patients who have
      an increased number of circulating protein macromolecules. It is a benign, in
      vitro reaction that appears microscopically as red blood cells (RBCs) line up
      against each other; many liken the RBC aggregation to "stacked coins." This
      unexpected reactivity may cause confusion in direct agglutination testing such as
      reverse blood typing and crossmatching. Saline replacement is the established
      method to resolve rouleaux. True agglutination will remain when plasma is
      replaced with saline for resuspension of the RBC button. Rouleaux will no longer
      be seen when the plasma proteins are removed.

PMID- 30295503
TI  - Method-specific and unexplained reactivity in automated solid-phase testing and
      their association with specific antibodies.
AB  - CONCLUSIONS: The inherent tradeoff between sensitivity and specificity in the
      detection of unexplained antibodies has been the objective of many studies,
      editorials, and journal articles. Many publications note that no method is
      capable of detecting all clinically significant antibodies while avoiding all
      clinically insignificant antibodies. This study describes the frequency of
      nonspecific reactivity and unexplained reactivity in solid-phase testing, along
      with the subsequent development of specific antibodies (Abs). In this study,
      nonspecific reactivity (NS) is defined as method-specific panreactivity detected
      by solid-phase testing only, with no reactivity in other methods. Unexplained
      reactivity (UR) is defined as reactivity present and detectable in all test
      methods after all clinically significant antibodies were ruled out following a
      standard antibody identification algorithm using selected cell panels. This
      retrospective study evaluated antibody detection tests of patients at a single
      center for 2 years using two automated solid-phase instruments that used the same
      three-cell antibody detection test. Antibody identification was performed with
      solid-phase panels supplemented with a polyethylene glycol tube method as needed.
      Of the 1934 (5%) samples with a positive antibody detection test, 29 had
      unavailable work-up data, leaving 1905 (98.5%) samples eligible for inclusion in
      the study. The data revealed the following: Ab only 999 (52.4%); UR only 429
      (22.5%); Ab and UR 227 (11.9%); NS only 206 (10.8%); Ab and NS 24 (1.3%); UR and
      NS 14 (0.7%); and Ab, UR, and NS 6 (0.3%). Patients with a positive follow-up
      antibody detection test had UR and NS replaced with a specific Ab in 23 of 656 UR
      (3%) and 8 of 230 NS (3%) cases, respectively. Additionally, six patients with UR
      developed a specific Ab along with persistent UR, and no patients with persistent
      NS developed a specific Ab. The study concluded that both UR and NS can be
      encountered in solid-phase testing, and both UR and NS can persist in follow-up
      testing. Specific Ab was observed to replace UR in a few patients.

PMID- 30295504
TI  - Utility of chloroquine diphosphate in the blood bank laboratory.
AB  - CONCLUSIONS: Chloroquine diphosphate (CDP) is a helpful tool in the blood bank
      for two main applications. The most common application is to render direct
      antiglobulin test-positive red blood cells (RBCs) free from membrane-bound IgG;
      these treated RBCs can then be used for autologous adsorption and/or to determine
      the patient's RBC phenotype. Another common use of CDP is to remove human
      leukocyte antigens (HLAs) from RBCs to help identify or exclude the presence of
      antibodies to HLAs expressed on RBCs, for example, Bennett-Goodspeed (Bg)
      antigens. In this review, the principles, applications, and limitations of using
      CDP are discussed.

PMID- 30295505
TI  - Clinical significance of antibodies to antigens in the Scianna, Dombrock, Colton,
      Landsteiner-Weiner, Chido/Rodgers, H, Kx, Cromer, Gerbich, Knops, Indian, and Ok
      blood group systems.
AB  - CONCLUSIONS: This article reviews information regarding the clinical significance
      of antibodies to antigens in the Scianna, Dombrock, Colton, Landsteiner-Wiener,
      Chido/Rodgers, H, Kx, Cromer, Gerbich, Knops, Indian, and Ok blood group systems.
      Like most blood group systems, antibodies to many of the antigens in these groups
      are rarely encountered because of the high prevalence of the associated antigens
      in most populations. For many, the clinical significance-that is, the potential
      to cause reduced survival of transfused antigen-positive red blood cells or a
      transfusion reaction (e.g., anti-Ge2, anti-H) and/or hemolytic disease of the
      fetus and newborn (e.g., anti-Coa, anti-Ge3)-has been documented. Some of these
      antibodies are not always clinically significant, and because of the high
      prevalence of the antigen, antigen-negative blood may be extremely difficult to
      find (e.g., anti-LW, anti-Inb). The use of a monocyte monolayer assay may be
      helpful when making transfusion decisions for patients with these antibodies. For
      others, their prevalence is so rare that information on the clinical significance
      of their antibodies is not available (e.g., anti-Co4, anti-Ok).

PMID- 30295506
TI  - A delayed and acute hemolytic transfusion reaction mediated by anti-c in a
      patient with variant RH alleles.
AB  - CONCLUSIONS: The Rh system is the most complex of the human blood groups. Of the
      55 antigens that have been characterized, the system's principal antigens D, C,
      E, c, and e are responsible for the majority of clinically significant Rh
      antibodies. In the last few years, advancements in molecular testing have
      provided a wealth of information on the genetic diversity of the Rh locus. This
      case report describes a patient with variant RHD*DAR alleles inherited in
      conjunction with two compound heterozygote RHCE*ceEK/RHCE*ceAR alleles. The
      patient was previously alloimmunized to D, C, and E and possibly hrS. Further
      transfusion of D-C-E-K- RBCs resulted in a suspected acute hemolytic transfusion
      reaction and the subsequent identification of anti-c. Monocyte monolayer assay
      testing suggests clinical significance with a range of 29.5-38.5 percent reactive
      monocytes.

PMID- 30295507
TI  - Detecting polyagglutinable red blood cells.
AB  - CONCLUSIONS: Polyagglutination is a condition in which red blood cells (RBCs) are
      agglutinated by normal adult human sera but not by autologous or newborn sera.
      Polyagglutination is caused by changes in the RBC membrane that enable patient
      RBCs to agglutinate with normal human sera; this agglutination can interfere with
      blood bank testing. Depending on the cause, polyagglutination may or may not be
      the cause of RBC hemolysis. Lectins and human sera can be used to detect
      polyagglutinable RBCs. Identification of this phenomenon can be helpful in
      providing not only transfusion recommendation information for physicians but also
      information associated with pathogens (i.e., Streptococcus pneumoniae) and
      severity of illness. Testing with ABO group-compatible adult human sera can
      determine if a patient's RBCs are polyagglutinable. Further testing with a variey
      of lectins may identify the kind of polyagglutination.

PMID- 30295508
TI  - Case Studies of the Impacts of Cataract Surgery on Crested Penguin Welfare.
AB  - As nonhuman animals age, geriatric individuals require additional care and
      veterinary support to ensure their well being. The focus on lifelong care is a
      relatively newer approach when providing good welfare, and few studies have
      examined how veterinary care impacts behavior at different ages or how best to
      accommodate geriatric individuals in zoos. The objectives of this study were to
      (a) assess both the immediate and long-term (one year later) behavioral impacts
      of cataract removal for macaroni (Eudyptes chrysolophus) and southern rockhopper
      (Eudyptes chrysocome) penguins; (b) compare the behavior of penguins following
      cataract surgery to that of other conspecifics in the same habitat; and (c)
      monitor the impacts of cataract surgery on swimming behavior using time-depth
      recorders. Individual responses to cataract removal differed in direction and
      magnitude, and these mixed results highlight that welfare is experienced and thus
      measured at the individual level. Positive responses included increased habitat
      use, increased time spent swimming, and increased rates of affiliative
      interactions. This study highlights the importance of assessing welfare impacts
      of veterinary interventions on geriatric individuals.

PMID- 30295509
TI  - Effects of obesity on insulin: insulin-like growth factor 1 hybrid receptor
      expression and Akt phosphorylation in conduit and resistance arteries.
AB  - Insulin and insulin-like growth factor-1 stimulate specific responses in
      arteries, which may be disrupted by diet-induced obesity. We examined (1)
      temporal effects of high-fat diet compared to low-fat diet in mice on insulin
      receptor, insulin-like growth factor-1 receptor, insulin receptor/insulin-like
      growth factor-1 receptor hybrid receptor expression and insulin/insulin-like
      growth factor-1-mediated Akt phosphorylation in aorta; and (2) effects of high
      fat diet on insulin and insulin-like growth factor-1-mediated Akt phosphorylation
      and vascular tone in resistance arteries. Medium-term high-fat diet (5 weeks)
      decreased insulin-like growth factor-1 receptor expression and increased hybrid
      expression (~30%) only. After long-term (16 weeks) high-fat diet, insulin
      receptor expression was reduced by ~30%, insulin-like growth factor-1 receptor
      expression decreased a further ~40% and hybrid expression increased a further
      ~60%. Independent correlates of hybrid receptor expression were high-fat diet,
      duration of high-fat diet and plasma insulin-like growth factor-1 (all p < 0.05).
      In aorta, insulin was a more potent activator of Akt than insulin-like growth
      factor-1, whereas in resistance arteries, insulin-like growth factor-1 was more
      potent than insulin. High-fat diet blunted insulin-mediated vasorelaxation ( p <
      0.01) but had no effect on insulin-like growth factor-1-mediated vasorelaxation
      in resistance arteries. Our findings support the possibility that hybrid receptor
      level is influenced by nutritional and metabolic cues. Moreover, vessel-dependent
      effects of insulin and insulin-like growth factor-1 on vascular tone and Akt
      activation may have implications in treating obesity-related vascular disease.

PMID- 30295510
TI  - Welfare of layers housed in small furnished cages on Danish commercial farms: the
      condition of keel bone, feet, plumage and skin.
AB  - 1. An on-farm assessment of keel bone, feet, plumage and skin damage was
      conducted in layers in small furnished cages to evaluate welfare implications. 2.
      Thirteen farms participated, all housing Lohmann LSL layers in systems allowing 8
      or 10 hens per cage. 3. Each flock was visited at three different ages: 32, 62
      and 77 weeks. During each visit, 100 hens were examined for keel bone fractures
      and deviations, plumage damage, body wounds, foot pad lesions, bumble feet,
      missing toes and toe wounds. 4. A deterioration with age of the condition of the
      plumage and keel bone was found (P < 0.001). At 77 weeks of age, 16% of the birds
      had poor plumage, and 43% of the birds had keel bone damage. In contrast, foot
      pad lesions were most prevalent at 32 weeks of age (13%), whereas the other foot
      injuries and body wounds remained at a relatively low level throughout the three
      ages examined. 5. Prevention of damage to the keel bone, plumage and foot pads
      should therefore be considered when aiming to improve welfare of laying hens
      housed in small furnished cages.

PMID- 30295512
TI  - A readily available improvement over method of moments for intra-cluster
      correlation estimation in the context of cluster randomized trials and fitting a
      GEE-type marginal model for binary outcomes.
AB  - Background/aims Cluster randomized trials are popular in health-related research
      due to the need or desire to randomize clusters of subjects to different trial
      arms as opposed to randomizing each subject individually. As outcomes from
      subjects within the same cluster tend to be more alike than outcomes from
      subjects within other clusters, an exchangeable correlation arises that is
      measured via the intra-cluster correlation coefficient. Intra-cluster correlation
      coefficient estimation is especially important due to the increasing awareness of
      the need to publish such values from studies in order to help guide the design of
      future cluster randomized trials. Therefore, numerous methods have been proposed
      to accurately estimate the intra-cluster correlation coefficient, with much
      attention given to binary outcomes. As marginal models are often of interest, we
      focus on intra-cluster correlation coefficient estimation in the context of
      fitting such a model with binary outcomes using generalized estimating equations.
      Traditionally, intra-cluster correlation coefficient estimation with generalized
      estimating equations has been based on the method of moments, although such
      estimators can be negatively biased. Furthermore, alternative estimators that
      work well, such as the analysis of variance estimator, are not as readily
      applicable in the context of practical data analyses with generalized estimating
      equations. Therefore, in this article we assess, in terms of bias, the readily
      available residual pseudo-likelihood approach to intra-cluster correlation
      coefficient estimation with the GLIMMIX procedure of SAS (SAS Institute, Cary,
      NC). Furthermore, we study a possible corresponding approach to confidence
      interval construction for the intra-cluster correlation coefficient. Methods We
      utilize a simulation study and application example to assess bias in intra
      cluster correlation coefficient estimates obtained from GLIMMIX using residual
      pseudo-likelihood. This estimator is contrasted with method of moments and
      analysis of variance estimators which are standards of comparison. The approach
      to confidence interval construction is assessed by examining coverage
      probabilities. Results Overall, the residual pseudo-likelihood estimator performs
      very well. It has considerably less bias than moment estimators, which are its
      competitor for general generalized estimating equation-based analyses, and
      therefore, it is a major improvement in practice. Furthermore, it works almost as
      well as analysis of variance estimators when they are applicable. Confidence
      intervals have near-nominal coverage when the intra-cluster correlation
      coefficient estimate has negligible bias. Conclusion Our results show that the
      residual pseudo-likelihood estimator is a good option for intra-cluster
      correlation coefficient estimation when conducting a generalized estimating
      equation-based analysis of binary outcome data arising from cluster randomized
      trials. The estimator is practical in that it is simply a result from fitting a
      marginal model with GLIMMIX, and a confidence interval can be easily obtained. An
      additional advantage is that, unlike most other options for performing
      generalized estimating equation-based analyses, GLIMMIX provides analysts the
      option to utilize small-sample adjustments that ensure valid inference.

PMID- 30295513
TI  - A rapid and scalable integrated membrane separation process for purification of
      polysaccharides from Enteromorpha prolifera.
AB  - An integrated membrane separation process combining the tubular ceramic
      microfiltration (MF) membrane and the flat-sheet ultrafiltration (UF) membrane
      was developed to purify polysaccharides from Enteromorpha prolifera. The effects
      of membrane pore size, molecular weight cut-off (MWCO), transmembrane pressure
      (TMP) and adding-water multiples on membrane performance were in-depth studied.
      The results indicated that the optimal membrane pore size and TMP of the tubular
      ceramic MF process were found to be 1.2 MUm and 0.225 MPa, and the optimal MWCO
      and TMP of the flat-sheet UF process were found to be 100 kDa and 0.3 MPa. The
      yields of polysaccharides were increased and optimized while the adding-water
      multiples was 1 during the diafiltration procedure. Furthermore, the water fluxes
      could be completely recovered using the specialized membrane cleaning methods,
      which ensured the reuse of membrane elements and satisfied the demands of
      industrial production. After purification by this integrated membrane separation
      process, the content of polysaccharides reached to 96.3%. The purified
      polysaccharides exhibited the superior moisture absorption and moisture retention
      properties compared to glycerol, polyethylene glycol (PEG) and luffa water.

PMID- 30295511
TI  - Tagetnoic acid, a new lipoxygenase inhibitor peroxy fatty acid from Tagetes
      minuta growing in Saudi Arabia.
AB  - A new peroxy fatty acid, tagetnoic acid (5) [4-((3S,6S)-6-((3E,8E)-octadeca-3,8
      dien-1-yl)-3,6-dihydro-1,2-dioxin-3-yl)butanoic acid] and four known metabolites:
      ecliptal (5-formyl-alpha-terthiophene) (1), 5-(4-hydroxybut-1-ynyl)-2,2'
      bithiophene (2), 22,23-dihydrospinasterone (3), and stigmasterol (4) were
      separated from the n-hexane fraction of the aerial parts of Tagetes minuta L.
      (Asteraceae). Their chemical structures were verified using IR, UV, 2D and 1D
      NMR, and HRMS. Compounds 3-5 displayed potent lipoxygenase inhibitory potential
      with IC50s 2.26, 1.83, and 1.17 MUM, respectively compared to indomethacin (IC50
      0.89 MUM). Moreover, molecular docking study revealed that the potent activity of
      5 is due to H-bonding and hydrophobic interaction. The results of this study
      suggested that Tagetes minuta dietary consumption would be useful for the
      individuals at risk of acute and chronic inflammatory disorders.

PMID- 30295514
TI  - Does self-efficacy in diabetes management differ by type of diabetes and gender?
      Results from network analysis.
AB  - This study aims to analyze the correlations and relevance of self-efficacy items
      in 411 patients with diabetes using network analysis. We found that the self
      efficacy items structure is consistent between genders and types of diabetes.
      However, the strength of item correlations was significantly higher in type 2
      diabetes. The items central to the network were following a regular diet in type
      2 diabetes and adjusting diet when ill in type 1 diabetes. No significant gender
      differences were found. Knowledge of the most central aspects of self-efficacy
      and their interconnections can help clinicians to target psychoeducational
      interventions aimed at empowering patients.

PMID- 30295515
TI  - An improved method for counting stressful life events (SLEs) when predicting
      mental health and wellness.
AB  - OBJECTIVE: Checklists for registering stressful life events (SLEs) generally
      correlate negatively, but weakly, with mental health outcome measures. Thus, the
      present study examined various methodological approaches for improving these
      relationships. DESIGN: A total of 1679 participants (women = 943, men = 736, M
      age-39.8) were randomly drawn from the general Norwegian population (response
      rate 34%). This prospective cohort study included two follow-ups at 10 (n = 1181)
      and 23 months (n = 942). MAIN OUTCOME MEASURES: Satisfaction with life and
      absence of psychological distress (i.e. anxiety and depression) represented a
      joint measure for indexing 'mental wellness' (MW). RESULTS: A simple count of
      SLEs weakly predicted MW, as expected, whereas the addition of a moderator (i.e.
      manageability of the event) substantially improved predictive power. Four
      additional moderators were examined: duration, impact, help-seeking and time
      since onset, but these were non-significant after inserting manageability into
      the model. This SLE counting method also retained its predictive power after
      including multiple criterion-related variables that substantially adjusted the
      longitudinal statistical model. CONCLUSION: This new SLE counting method
      exhibited a considerable improvement to predicting mental health and well-being.
      It is well suited for use in epidemiological research requiring a short SLE
      checklist format with high predictive power.

PMID- 30295516
TI  - Efficacy of a computer-based cognitive training program to enhance planning
      skills in 5 to 7-year-old normally-developing children.
AB  - We designed and evaluated the efficacy of a computer-based cognitive training
      program (Executive Function Enhancement Program [EFEP]) to stimulate executive
      functions through enhancing planning in normally-developing children. A total of
      111 Colombian children participated in the study. Fifty-nine (53%) of the
      children were assigned to the experimental condition (application of the EFEP
      program) with two levels of planning performance, and fifty-two (47%) to the
      waiting list control condition with the same two levels of planning. The training
      program was applied three times a week over six weeks, with post-intervention
      assessment two weeks after the end of training. A follow-up assessment was
      carried out three months later. Results showed that the intervention program was
      particularly effective in the children with lower pre-intervention performance in
      planning, demonstrating that the program is an efficient therapeutic instrument
      for enhancing the executive function of planning in children between 5 and 7
      years old.

PMID- 30295517
TI  - Neuropsychological assessment of Chilean children with a history of extreme
      prematurity: An exploratory study.
AB  - This study was conducted to explore the neuropsychological abilities of premature
      Chilean children. Two groups (Premature and Control, 10 children each, age
      ranging from 5 to 7.11) were established based on weeks of gestation and/or
      weight at birth. Relevant variables such as age, gender, schooling, and
      socioeconomic level were matched considering Chile's particular demographic
      context. Children were assessed by means of the Evaluacion Neuropsicologica
      Infantil (ENI-2) battery, measuring nine cognitive domains encompassing 23
      subscales. In turn, subscales are grouped in two scales: Cognitive Functions and
      Executive Functions. Since the ENI-2 battery provides norms for Spanish-speaking
      children, obtained data were inspected both for possible between-group
      differences and either adjustment or deviance from average range. Results show
      that premature children perform within typical ranges in all subscales except for
      Visual attention and Graphic fluency. When comparing both groups, some
      differences emerged. These differences are most prominent in subscales related to
      visuoperceptual skills. Interestingly, between-group linguistic performance is
      very similar. The point is made that early linguistic interventions conducted on
      premature children seem to positively impact on oral language expression and
      comprehension. On the contrary, early interventions focused on visuospatial
      abilities did not seem to attain the same impact. This may be a consequence of
      visual-information processing problems derived from cortical dorsal stream's
      vulnerability, which literature correlates with prematurity.

PMID- 30295518
TI  - Trends in the surgical treatment of pathological fractures of the long bones.
AB  - AIMS: The aim of this study was to assess the current trends in the estimation of
      survival and the preferred forms of treatment of pathological fractures among
      national and international general and oncological orthopaedic surgeons, and to
      explore whether improvements in the management of these patients could be
      identified in this way. MATERIALS AND METHODS: All members of the Dutch
      Orthopaedic Society (DOS) and the European Musculoskeletal Oncology Society
      (EMSOS) were invited to complete a web-based questionnaire containing 12 cases.
      RESULTS: A total of 96 of 948 members of the DOS (10.1%; groups 1 and 2) and 33
      of 182 members of the EMSOS (18%; group 3) replied. The estimation of survival
      was accurate by more than 50% of all three groups, if the expected survival was
      short (< 3 months) or long (> 12 months). General orthopaedic surgeons preferred
      using an intramedullary nail for fractures of the humerus and femur, irrespective
      of the expected survival or the origin of primary tumour or the location of the
      fracture. Oncological orthopaedic surgeons recommended prosthetic reconstruction
      in patients with a long expected survival. CONCLUSION: Identifying patients who
      require centralized care, as opposed to those who can be adequately treated in a
      regional centre, can improve the management of patients with pathological
      fractures. This differentiation should be based on the expected survival, the
      type and extent of the tumour, and the location of the fracture. Cite this
      article: Bone Joint J 2018;100-B:1392-8.

PMID- 30295519
TI  - Predicted final spinal height in patients with adolescent idiopathic scoliosis
      can be achieved by surgery regardless of maturity status.
AB  - AIMS: The aim of this study was to investigate the impact of maturity status at
      the time of surgery on final spinal height in patients with an adolescent
      idiopathic scoliosis (AIS) using the spine-pelvic index (SPI). The SPI is a self
      control ratio that is independent of age and maturity status. PATIENTS AND
      METHODS: The study recruited 152 female patients with a Lenke 1 AIS. The
      additional inclusion criteria were a thoracic Cobb angle between 45 degrees  and
      70 degrees , Risser 0 to 1 or 3 to 4 at the time of surgery, and follow-up until
      18 years of age or Risser stage 5. The patients were stratified into four groups:
      Risser 0 to 1 and selective fusion surgery (Group 1), Risser 0 to 1 and non
      selective fusion (Group 2), Risser 3 to 4 and selective fusion surgery (Group 3),
      and Risser 3 to 4 and non-selective fusion (Group 4). The height of spine at
      follow-up (HOSf) and height of pelvis at follow-up (HOPf) were measured and the
      predicted HOS (pHOS) was calculated as 2.22 (SPI) * HOPf. One-way analysis of
      variance (ANOVA) was performed for statistical analysis. RESULTS: Of the 152
      patients, there were 32 patients in Group 1, 27 patients in Group 2, 48 patients
      in Group 3, and 45 patients in Group 4. Significantly greater HOSf was observed
      in Group 3 compared with Group 1 (p = 0.03) and in Group 4 compared with Group 2
      (p = 0.02), with similar HOPf (p = 0.75 and p = 0.83, respectively), suggesting
      that patients who undergo surgery at Risser grade of 0 to 1 have a shorter spinal
      height at follow-up than those who have surgery at Risser 4 to 5. HOSf was
      similar to pHOS in both Group 1 and Group 2 (p = 0.62 and p = 0.45,
      respectively), indicating that undergoing surgery at Risser 0 to 1 does not
      necessarily affect final spinal height. CONCLUSION: This study shows that fusion
      surgery at Risser 0 may result in growth restriction unlike fusion surgery at
      Risser 3 to 4. Despite such growth restriction, AIS patients could reach their
      predicted or 'normal' spinal height after surgery regardless of baseline maturity
      status due to the longer baseline spinal length in AIS patients and the remaining
      growth potential at the non-fusion levels. Cite this article: Bone Joint J
      2018;100-B:1372-6.

PMID- 30295520
TI  - Meta-analysis: well-established and here to stay.

PMID- 30295521
TI  - Comparison of molecular diagnosis with serum markers and synovial fluid analysis
      in patients with prosthetic joint infection.
AB  - AIMS: The aim of this study was to compare the results of 16S/28S rRNA sequencing
      with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level,
      and synovial fluid analysis in the diagnosis of prosthetic joint infection (PJI).
      PATIENTS AND METHODS: Between September 2015 and August 2016, 214 consecutive
      patients were enrolled. In the study population, there were 25 patients with a
      PJI and 189 controls. Of the PJI patients, 14 (56%) were women, and the mean age
      at the time of diagnosis was 65 years (38 to 83). The ESR and CRP levels were
      measured, and synovial fluid specimens were collected prospectively. Synovial
      fluid was subjected to reverse transcription polymerase chain reaction (RT
      PCR)/sequence analysis targeting the 16S/28S rRNA, and to conventional culture.
      Laboratory personnel who were blind to the clinical information performed all
      tests. The diagnosis of PJI was based on the criteria of the Musculoskeletal
      Infection Society. RESULTS: A total of 25 patients had a confirmed PJI. In 20
      cases of monomicrobial PJI, the PCR products could be perfectly matched with the
      16S/28S rRNA genes specific for different species of bacteria provided by
      sequence analysis. Of the five polymicrobial cases of PJI, 16S/28S rRNA PCR
      sequence analysis failed to identify the concordant bacteria species. In the 189
      control patients, there was one false-positive RT-PCR result. The sensitivity and
      specificity of the molecular diagnosis method were 100% (95% confidence interval
      (CI) 85.7 to 100) and 99.5% (95% CI 97.1 to 99.9), respectively, whereas the
      positive and negative predictive values of PCR were 96.1% (95% CI 79.6 to 99.9)
      and 100% (95% CI 98.1 to 100), respectively. The PCR results were significantly
      better than serological diagnostic methods (p = 0.004 and p = 0.010 for ESR and
      CRP, respectively), the synovial fluid white blood cell (WBC) count (p = 0.036),
      and percentage of polymorphonuclear cells (PMN%) (p = 0.014). CONCLUSION:
      Stepwise RT-PCR and sequence analysis of the 16S/28S rRNA carried out under
      stringent laboratory conditions achieved highly sensitive and specific results
      for the differentiation between aseptic and septic joints undergoing
      arthroplasty. Sequence analysis successfully identified bacterial strains in
      monomicrobial infections but failed to identify molecular targets in
      polymicrobial infections. Further refinement of the protocols to identify the
      bacteria in polymicrobial infections is needed. Cite this article: Bone Joint J
      2018;100-B:1345-51.

PMID- 30295522
TI  - The cost-effectiveness of dual mobility in a spinal deformity population with
      high risk of dislocation.
AB  - AIMS: The routine use of dual-mobility (DM) acetabular components in total hip
      arthroplasty (THA) may not be cost-effective, but an increasing number of
      patients undergoing THA have a coexisting spinal disorder, which increases the
      risk of postoperative instability, and these patients may benefit from DM
      articulations. This study seeks to examine the cost-effectiveness of DM
      components as an alternative to standard articulations in these patients.
      PATIENTS AND METHODS: A decision analysis model was used to evaluate the cost
      effectiveness of using DM components in patients who would be at high risk for
      dislocation within one year of THA. Direct and indirect costs of dislocation,
      incremental costs of using DM components, quality-adjusted life-year (QALY)
      values, and the probabilities of dislocation were derived from published data.
      The incremental cost-effectiveness ratio (ICER) was established with a
      willingness-to-pay threshold of $100 000/QALY. Sensitivity analysis was used to
      examine the impact of variation. RESULTS: In the base case, patients with a
      spinal deformity were modelled to have an 8% probability of dislocation following
      primary THA based on published clinical ranges. Sensitivity analysis revealed
      that, at its current average price ($1000), DM is cost-effective if it reduces
      the probability of dislocation to 0.9%. The threshold cost at which DM ceased
      being cost-effective was $1180, while the ICER associated with a DM THA was $71
      000 per QALY. CONCLUSION: These results indicate that under specific clinical and
      economic thresholds, DM components are a cost-effective form of treatment for
      patients with spinal deformity who are at high risk of dislocation after THA.
      Cite this article: Bone Joint J 2018;100-B:1297-1302.

PMID- 30295523
TI  - The effectiveness of ultra-clean air operating theatres in the prevention of deep
      infection in joint arthroplasty surgery.
AB  - Deep infection was identified as a serious complication in the earliest days of
      total hip arthroplasty. It was identified that airborne contamination in
      conventional operating theatres was the major contributing factor. As progress
      was made in improving the engineering of operating theatres, airborne
      contamination was reduced. Detailed studies were carried out relating airborne
      contamination to deep infection rates. In a trial conducted by the United Kingdom
      Medical Research Council (MRC), it was found that the use of ultra-clean air
      (UCA) operating theatres was associated with a significant reduction in deep
      infection rates. Deep infection rates were further reduced by the use of a body
      exhaust system. The MRC trial also included a detailed microbiology study, which
      confirmed the relationship between airborne contamination and deep infection
      rates. Recent observational evidence from joint registries has shown that in
      contemporary practice, infection rates remain a problem, and may be getting
      worse. Registry observations have also called into question the value of "laminar
      flow" operating theatres. Observational evidence from joint registries provides
      very limited evidence on the efficacy of UCA operating theatres. Although there
      have been some changes in surgical practice in recent years, the conclusions of
      the MRC trial remain valid, and the use of UCA is essential in preventing deep
      infection. There is evidence that if UCA operating theatres are not used
      correctly, they may have poor microbiological performance. Current UCA operating
      theatres have limitations, and further research is required to update them and
      improve their microbiological performance in contemporary practice. Cite this
      article: Bone Joint J 2018;100-B:1264-9.

PMID- 30295524
TI  - Repeat epidural steroid injections for radicular pain due to lumbar or cervical
      disc herniation.
AB  - AIMS: The aim of this study was to determine the efficacy of repeat epidural
      steroid injections as a form of treatment for patients with insufficiently
      controlled or recurrent radicular pain due to a lumbar or cervical disc
      herniation. PATIENTS AND METHODS: A cohort of 102 patients was prospectively
      followed, after an epidural steroid injection for radicular symptoms due to
      lumbar disc herniation, in 57 patients, and cervical disc herniation, in 45
      patients. Those patients with persistent pain who requested a second injection
      were prospectively followed for one year. Radicular and local pain were assessed
      on a visual analogue scale (VAS), functional outcome with the Oswestry Disability
      Index (ODI) or the Neck Pain and Disability Index (NPAD), as well as health
      related quality of life (HRQoL) using the 12-Item Short-Form Health Survey
      questionnaire (SF-12). RESULTS: A second injection was performed in 17 patients
      (29.8%) with lumbar herniation and seven (15.6%) with cervical herniation at a
      mean of 65.3 days (sd 46.5) and 47 days (sd 37.2), respectively, after the
      initial injection. All but one patient, who underwent lumbar microdiscectomy,
      responded satisfactorily with a mean VAS for leg pain of 8.8 mm (sd 10.3) and a
      mean VAS for arm pain of 6.3 mm (sd 9) one year after the second injection,
      respectively. Similarly, functional outcome and HRQoL were improved significantly
      from the baseline scores: mean ODI, 12.3 (sd 12.4; p < 0.001); mean NPAD, 19.3
      (sd 24.3; p = 0.041); mean SF-12 physical component summary (PCS) in lumbar
      herniation, 46.8 (sd 7.7; p < 0.001); mean SF-12 PCS in cervical herniation, 43
      (sd 6.8; p = 0.103). CONCLUSION: Repeat steroid injections are a justifiable form
      of treatment in symptomatic patients with lumbar or cervical disc herniation
      whose symptoms are not satisfactorily relieved after the first injection. Cite
      this article: Bone Joint J 2018;100-B:1364-71.

PMID- 30295525
TI  - Material loss at the femoral head taper.
AB  - AIMS: There are limited published data detailing the volumetric material loss
      from tapers of conventional metal-on-polyethylene (MoP) total hip arthroplasties
      (THAs). Our aim was to address this by comparing the taper wear rates measured in
      an explanted cohort of the widely used Exeter THA with those measured in a group
      of metal-on-metal (MoM) THAs. PATIENTS AND METHODS: We examined an existing
      retrieval database to identify all Exeter V40 and Universal MoP THAs. Volumetric
      wear analysis of the taper surfaces was conducted using previously validated
      methodology. These values were compared with those obtained from a series of MoM
      THAs using non-parametric statistical methodology. A number of patient and device
      variables were accounted for using multiple regression modelling. RESULTS: A
      total of 95 Exeter MoP and 249 MoM THAs were examined. The median volumetric loss
      from the MoM cohort was over four times larger than that from the MoP cohort
      (1.01 mm3 vs 0.23 mm3, p < 0.001), despite a significantly shorter median period
      in vivo for the MoM group (48 months vs 90 months, p < 0.001). Multiple
      regression modelling indicated that the dominant variables leading to greater
      female taper material loss were bearing diameter (p < 0.001), larger female taper
      angles (p < 0.001), and male titanium stem tapers (p < 0.001). CONCLUSION:
      Consistent with the long-term clinical success of the device, the volumetric
      material loss from Exeter femoral head tapers was, in general, small compared
      with that from larger-diameter MoM head tapers. Cite this article: Bone Joint J
      2018;100-B:1310-9.

PMID- 30295526
TI  - Results of universal ultrasound screening for developmental dysplasia of the hip.
AB  - AIMS: The purpose of this study was to analyze the incidence of the different
      ultrasound phenotypes of developmental dysplasia of the hip (DDH), and to
      determine their subsequent course. PATIENTS AND METHODS: A consecutive series of
      28 092 neonates was screened and classified according to the Graf method as part
      of a nationwide surveillance programme, and then followed prospectively. Abnormal
      hips were followed until they became normal (Graf type I). Type IIb hips and
      higher grades were treated by abduction in a Tubinger orthosis until normal.
      Dislocated hips underwent closed or open reduction. RESULTS: Overall, 90.2% of
      hips were normal at birth. Type IIa hips (8.9%) became normal at a median of six
      weeks (interquartile range (IQR) 6 to 9). Type IIc and IId hips (0.67%) became
      normal after ten weeks (IQR 7 to 13). There were 19 type lll and eight type lV
      hips at baseline. There were 24 closed reductions and one open reduction. No late
      presentations of DDH were detected within the first five years of life.
      CONCLUSION: The incidence of DDH was eight per 1000 live births. The treatment
      rate was 1% (n = 273). The rate of first operations on the newborn hip was 0.86,
      and rate of open surgery was 0.04. The cumulative rate of open surgery was 0.07.
      The authors take the view that early identification and treatment in abduction of
      all dysplastic hips in early childhood reduces the rate of open reduction and
      secondary DDH-related surgery later in life. Cite this article: Bone Joint J
      2018;100-B:1399-1404.

PMID- 30295527
TI  - Total ankle arthroplasty: what are the risks?
AB  - AIMS: Total ankle arthroplasty (TAA) surgery is complex and attracts a wide
      variety of complications. The literature lacks consistency in reporting adverse
      events and complications. The aim of this article is to provide a comprehensive
      analysis of each of these complications from a literature review, and to compare
      them with rates from our Unit, to aid clinicians with the process of informed
      consent. PATIENTS AND METHODS: A total of 278 consecutive total ankle
      arthroplasties (251 patients), performed by four surgeons over a six-year period
      in Wrightington Hospital (Wigan, United Kingdom) were prospectively reviewed.
      There were 143 men and 108 women with a mean age of 64 years (41 to 86). The data
      were recorded on each follow-up visit. Any complications either during initial
      hospital stay or subsequently reported on follow-ups were recorded, investigated,
      monitored, and treated as warranted. Literature search included the studies
      reporting the outcomes and complications of TAA implants. RESULTS: There were
      wound-healing problems in nine ankles (3.2%), superficial infection in 20 ankles
      (7.2%), and deep infection in six ankles (2.2%). Intraoperative fractures
      occurred in medial malleoli in 27 ankles (9.7%) and in lateral malleoli in four
      ankles (1.4%). Aseptic loosening and osteolysis were seen 16 ankles (5.8%).
      Fracture of the polyethylene component occurred in one ankle (0.4%) and edge
      loading in seven ankles (2.5%). We observed medial gutter pain in 31 ankles
      (11.1%). The incidence of thromboembolism occurred in two ankles (0.7%). The
      results were found to be comparable to the previously reported complications of
      total ankle arthroplasty in the literature. CONCLUSION: Total ankle arthroplasty
      continues to evolve and improve the ankle function. Despite high overall
      complication rates with TAA surgery, most complications appear to be minor and do
      not affect final clinical outcome. Our results and literature review will help in
      the consent process and provide detailed complication rates for an informed
      consent. Cite this article: Bone Joint J 2018;100-B:1352-8.

PMID- 30295528
TI  - Antioxidant-stabilized highly crosslinked polyethylene in total knee
      arthroplasty.
AB  - AIMS: The aim of this study was to evaluate the surface damage, the density of
      crosslinking, and oxidation in retrieved antioxidant-stabilized highly
      crosslinked polyethylene (A-XLPE) tibial inserts from total knee arthroplasty
      (TKA), and to compare the results with a matched cohort of standard remelted
      highly crosslinked polyethylene (XLPE) inserts. MATERIALS AND METHODS: A total of
      19 A-XLPE tibial inserts were retrieved during revision TKA and matched to 18
      retrieved XLPE inserts according to the demographics of the patients, with a mean
      length of implantation of 15 months (1 to 42). The percentage areas of PE damage
      on the articular surfaces and the modes of damage were measured. The density of
      crosslinking of the PE and oxidation were measured at loaded and unloaded regions
      on these surfaces. RESULTS: A-XLPE inserts had higher rates of burnishing and
      lower rates of pitting and scratching compared with XLPE. There were no
      differences in the density of crosslinking at loaded and unloaded regions. A-XLPE
      showed higher oxidation indices in the unloaded surface region compared with
      XLPE. There were no differences in the levels of oxidation in the loaded regions.
      CONCLUSION: Retrieval analysis of A-XLPE did not reflect a clinically relevant
      difference in surface damage, density of crosslinking, or oxidation compared with
      XLPE tibial inserts at short-term evaluation. Cite this article: Bone Joint J
      2018;100-B:1330-5.

PMID- 30295529
TI  - Chopart amputation with tibiotalocalcaneal arthrodesis and free flap
      reconstruction for severe foot crush injury.
AB  - AIMS: This study reports the outcomes of a technique of soft-tissue coverage and
      Chopart amputation for severe crush injuries of the forefoot. PATIENTS AND
      METHODS: Between January 2012 to December 2016, 12 patients (nine male; three
      female, mean age 38.58 years; 26 to 55) with severe foot crush injury underwent
      treatment in our institute. All patients were followed-up for at least one year.
      Their medical records, imaging, visual analogue scale score, walking ability,
      complications, and functional outcomes one year postoperatively based on the
      American Orthopedic Foot and Ankle Society (AOFAS) and 36-Item Short-Form Health
      Survey (SF-36) scores were reviewed. RESULTS: The mean length of follow-up was
      18.6 months (13 to 28). Two patients had a local infection, flap necrosis was
      seen in one patient, and one patient experienced a skin graft wound healing
      delay. Of the 12 patients, one had persistent infection and eventually required
      below-knee amputation, but pain-free walking was achieved in all the other
      patients. The mean one-year postoperative AOFAS and SF-36 scores were 75.6 (68 to
      80) and 82 (74 to 88), respectively. CONCLUSION: Although our sample size was
      small, we believe that this treatment method may be a valuable alternative for
      treating severe foot crush injuries. Cite this article: Bone Joint J 2018;100
      B:1359-63.

PMID- 30295530
TI  - Temporal trends and survivorship of total hip arthroplasty in very young
      patients.
AB  - AIMS: The aim of this study was to describe temporal trends and survivorship of
      total hip arthroplasty (THA) in very young patients, aged <= 20 years. PATIENTS
      AND METHODS: A descriptive observational study was undertaken using data from the
      National Joint Registry (NJR) for England, Wales, Northern Ireland and the Isle
      of Man between April 2003 and March 2017. All patients aged <= 20 years at the
      time of THA were included and the primary outcome was revision surgery.
      Descriptive statistics were used to summarize the data and Kaplan-Meier estimates
      calculated for the cumulative implant survival. RESULTS: A total of 769 THAs were
      performed in 703 patients. The median follow-up was 5.1 years (interquartile
      range (IQR) 2.6 to 7.8). Eight patients died and 35 THAs were revised. The use of
      metal-on-metal (MoM) bearings and resurfacing procedures declined after 2008. The
      most frequently recorded indications for revision were loosening (20%) and
      infection (20%), although the absolute risk of these events occurring was low
      (0.9%). Factors associated with lower implant survival were MoM and metal-on
      polyethylene (MoP) bearings and resurfacing arthroplasty ( vs ceramic-on
      polyethylene (CoP) and ceramic-on-ceramic (CoC) bearings, p = 0.002), and
      operations performed by surgeons who undertook few THAs in this age group as
      recorded in the NJR ( vs those with five or more recorded operations, p = 0.030).
      Kaplan-Meier estimates showed 96% (95% confidence interval (CI) 94% to 98%)
      survivorship of implants at five years. CONCLUSION: Within the NJR, the overall
      survival for very young patients undergoing THA exceeded 96% during the first
      five postoperative years. In the absence of studies that can better account for
      differences in the characteristics of the patients, surgeons should consider the
      association between early revision and the type of implant, the number of THAs
      performed in these patients, and the bearing surface when performing THA in very
      young patients. Cite this article: Bone Joint J 2018;100-B:1320-9.

PMID- 30295531
TI  - The role of lumbar lordosis and pelvic sagittal balance in femoroacetabular
      impingement.
AB  - AIMS: The purpose of this study was to evaluate spinopelvic mechanics from
      standing and sitting positions in subjects with and without femoroacetabular
      impingement (FAI). We hypothesize that FAI patients will experience less flexion
      at the lumbar spine and more flexion at the hip whilst changing from standing to
      sitting positions than subjects without FAI. This increase in hip flexion may
      contribute to symptomatology in FAI. PATIENTS AND METHODS: Male subjects were
      prospectively enrolled to the study (n = 20). Mean age was 31 years old (22 to
      41). All underwent clinical examination, plain radiographs, and dynamic imaging
      using EOS. Subjects were categorized into three groups: non-FAI (no radiographic
      or clinical FAI or pain), asymptomatic FAI (radiographic and clinical FAI but no
      pain), and symptomatic FAI (patients with both pain and radiographic FAI). FAI
      was defined as internal rotation less than 15 degrees  and alpha angle greater
      than 60 degrees . Subjects underwent standing and sitting radiographs in order to
      measure spine and femoroacetabular flexion. RESULTS: Compared with non-FAI
      controls, symptomatic patients with FAI had less flexion at the spine (mean 22
      degrees , sd 12 degrees , vs mean 35 degrees , sd 8 degrees ; p = 0.04) and more
      at the hip (mean 72 degrees , sd 6 degrees , vs mean 62 degrees , sd 8 degrees ;
      p = 0.047). Subjects with asymptomatic FAI had more spine flexion and similar hip
      flexion when compared to symptomatic FAI patients. Both FAI groups also sat with
      more anterior pelvic tilt than control patients. There were no differences in
      standing alignment among groups. CONCLUSION: Symptomatic patients with FAI
      require more flexion at the hip to achieve sitting position due to their
      inability to compensate through the lumbar spine. With limited spine flexion, FAI
      patients sit with more anterior pelvic tilt, which may lead to impingement
      between the acetabulum and proximal femur. Differences in spinopelvic mechanics
      between FAI and non-FAI patients may contribute to the progression of FAI
      symptoms. Cite this article: Bone Joint J 2018;100-B:1275-9.

PMID- 30295532
TI  - A systematic review of meta-analyses in orthopaedic surgery between 2000 and
      2016.
AB  - AIMS: The aims of this systematic review were to describe the quantity and
      methodological quality of meta-analyses in orthopaedic surgery published during
      the last 17 years. MATERIALS AND METHODS: MEDLINE, EMBASE, and PubMed, between 1
      January 2000 and 31 December 2016, were searched for meta-analyses in orthopaedic
      surgery dealing with at least one surgical intervention. Meta-analyses were
      included if the interventions involved a human muscle, ligament, bone or joint.
      RESULTS: A total of 392 meta-analyses met eligibility criteria, for which the
      mean AMSTAR quality score was 7.1/11. There was a positive correlation between
      the year of publication and the quality of the meta-analysis (r = 0.238, p <
      0.001). Between 2000 and 2011, the mean AMSTAR score corresponded to that of a
      medium quality review. However, between 2012 and 2016, the mean scores have been
      consistently equivalent to those of a high-quality review. The number of meta
      analyses published increased 10-fold between 2005 and 2014. CONCLUSION: The
      quantity and quality of meta-analyses in orthopaedic surgery which have been
      published has increased, reaching a plateau in 2012. Methodological flaws remain
      to be addressed in future meta-analyses in order to continue increasing the
      quality of the orthopaedic literature. Cite this article: Bone Joint J 2018;100
      B:1270-4.

PMID- 30295533
TI  - Functional acetabular component alignment.

PMID- 30295534
TI  - What preoperative factors predict postoperative sitting pelvic position one year
      following total hip arthroplasty?
AB  - AIMS: The aims of this study were to measure sagittal standing and sitting lumbar
      pelvic-femoral alignment in patients before and following total hip arthroplasty
      (THA), and to consider what preoperative factors may influence a change in
      postoperative pelvic position. PATIENTS AND METHODS: A total of 161 patients were
      considered for inclusion. Patients had a mean age of the remaining 61 years (sd
      11) with a mean body mass index (BMI) of 28 kg/m2 (sd 6). Of the 161 patients, 82
      were male (51%). We excluded 17 patients (11%) with spinal conditions known to
      affect lumbar mobility as well as the rotational axis of the spine. Standing and
      sitting spine-to-lower-limb radiographs were taken of the remaining 144 patients
      before and one year following THA. Spinopelvic alignment measurements, including
      sacral slope, lumbar lordosis, and pelvic incidence, were measured. These angles
      were used to calculate lumbar spine flexion and femoroacetabular hip flexion from
      a standing to sitting position. A radiographic scoring system was used to
      identify those patients in the series who had lumbar degenerative disc disease
      (DDD) and compare spinopelvic parameters between those patients with DDD (n = 38)
      and those who did not (n = 106). RESULTS: Following THA, patients sat with more
      anterior pelvic tilt (mean increased sacral slope 18 degrees  preoperatively
      versus 23 degrees  postoperatively; p = 0.001) and more lumbar lordosis (mean 28
      degrees  preoperatively versus 35 degrees  postoperatively; p = 0.001).
      Preoperative change in sacral slope from standing to sitting (p = 0.03) and the
      absence of DDD (p = 0.001) correlated to an increased change in postoperative
      sitting pelvic alignment. CONCLUSION: Sitting lumbar-pelvic-femoral alignment
      following THA may be driven by hip arthritis and/or spinal deformity. Patients
      with DDD and fixed spinopelvic alignment have a predictable pelvic position one
      year following THA. Patients with normal spines have less predictable
      postoperative pelvic position, which is likely to be driven by hip stiffness.
      Cite this article: Bone Joint J 2018;100-B:1289-96.

PMID- 30295535
TI  - Increased complications in geriatric patients with a fracture of the hip whose
      postoperative weight-bearing is restricted.
AB  - AIMS: The aims of this study were to evaluate the incidence of postoperatively
      restricted weight-bearing and its association with outcome in patients who
      undergo surgery for a fracture of the hip. PATIENTS AND METHODS: Patient aged >
      60 years undergoing surgery for a hip fracture were identified in the 2016
      National Surgical Quality Improvement Program (NSQIP) Hip Fracture Targeted
      Procedure Dataset. Analysis of the effect of restricted weight-bearing on adverse
      events, delirium, infection, transfusion, length of stay, return to the operating
      theatre, readmission and mortality within 30 days postoperatively were assessed.
      Multivariate regression analysis was used to adjust for confounding demographic,
      comorbid and procedural characteristics. RESULTS: Of the 4918 patients who met
      inclusion criteria, 3668 (63.53%) were allowed to weight-bear as tolerated
      postoperatively. Controlling for patient and procedural factors, multivariate
      odds of any adverse event, major adverse event, delirium, infection, transfusion,
      length of stay >= 75th percentile (six days) and mortality within 30 days were
      all higher in patients with weight-bearing restrictions. Notably, there were no
      differences for thromboembolic events, return to the operating theatre or
      readmission within 30 days between the groups. CONCLUSION: Elderly patients with
      a fracture of the hip with postoperative weight-bearing restrictions have a
      significantly greater risk of developing most adverse events compared with those
      who are encouraged to weight-bear as tolerated. These findings emphasize the
      importance of immediate weight-bearing as tolerated to optimize the outcome in
      these frail patients; however nearly 25% of surgeons fail to meet this evidence
      based guideline. Cite this article: Bone Joint J 2018;100-B:1377-84.

PMID- 30295536
TI  - Plate fixation compared with nonoperative treatment of displaced midshaft
      clavicular fractures: a randomized clinical trial.
AB  - AIMS: Recent studies of nonoperatively treated displaced midshaft clavicular
      fractures have shown a high incidence of nonunion and unsatisfactory functional
      outcome. Some studies have shown superior functional results and higher rates of
      healing following operative treatment. The aim of this study was to compare the
      outcome in these patients after nonoperative management with those treated with
      fixation. PATIENTS AND METHODS: In a multicentre, parallel randomized controlled
      trial, 146 adult patients with an acute displaced fracture of the midthird of the
      clavicle were randomized to either nonoperative treatment with a sling (71, 55
      men and 16 women with a mean age of 39 years, 18 to 60) or fixation with a pre
      contoured plate and locking screws (75, 64 men and 11 women with a mean age of 40
      years, 18 to 60). Outcome was assessed using the Disabilities of the Arm,
      Shoulder and Hand (DASH) Score, the Constant Score, and radiographical evidence
      of union. Patients were followed for one year. RESULTS: A total of 60 patients in
      the nonoperative group and 64 in the operative group completed one-year follow
      up. At three months' follow-up, both the median DASH (1.7 vs 8.3) and median
      Constant scores (97 vs 90) were significantly better in the operated group (both
      p = 0.02). After six months and one year, there was no difference in the median
      DASH or Constant scores. The rate of nonunion was lower in the operative group (2
      vs 11 patients, p < 0.02). Nine patients in the nonoperative group underwent
      surgery for nonunion. The plate was subsequently removed in 16 patients (25%).
      One patient had a new fracture after removal of the plate and one underwent
      revision surgery for failure of fixation. CONCLUSION: Fixation of a displaced
      midshaft clavicular fracture using a pre-contoured plate and locking screws
      results in faster functional recovery and a higher rate of union compared with
      nonoperative management, but the function of the shoulder is equal after six
      months and at one year. Cite this article: Bone Joint J 2018;100-B:1385-91.

PMID- 30295537
TI  - Pelvic positioning in the supine position leads to more consistent orientation of
      the acetabular component after total hip arthroplasty.
AB  - AIMS: This study aims to: determine the difference in pelvic position that occurs
      between surgery and radiographic, supine, postoperative assessment; examine how
      the difference in pelvic position influences subsequent component orientation;
      and establish whether differences in pelvic position, and thereafter component
      orientation, exist between total hip arthroplasties (THAs) performed in the
      supine versus the lateral decubitus positions. PATIENTS AND METHODS: The intra-
      and postoperative anteroposterior pelvic radiographs of 321 THAs were included;
      167 were performed with the patient supine using the anterior approach and 154
      were performed with the patient in the lateral decubitus using the posterior
      approach. The inclination and anteversion of the acetabular component was
      measured and the difference (Delta) between the intra- and postoperative
      radiographs was determined. The target zone was inclination/anteversion of 40
      degrees /20 degrees  (+/- 10 degrees ). Changes in the tilt, rotation, and
      obliquity of the pelvis on the intra- and postoperative radiographs were
      calculated from Deltainclination/anteversion using the Levenberg-Marquardt
      algorithm. RESULTS: The mean postoperative inclination/anteversion was 40 degrees
      (+/- 8 degrees )/23 degrees  (+/- 9 degrees ) with Deltainclination and/or
      Deltaanteversion > +/- 10 degrees  in 74 (21%). Intraoperatively, the pelvis was
      anteriorly tilted by a mean of 4 degrees  (+/- 10 degrees ), internally rotated
      by a mean of 1 degrees  (+/- 10 degrees ) and adducted by a mean of 1 degrees 
      (+/- 5 degrees ). Having Deltainclination and/or Deltaanteversion > +/- 10
      degrees  was associated with a 3.5 odds ratio of having the acetabular component
      outside the target zone. A greater proportion of THAs that were undertaken with
      the patient in the lateral decubitus position had Deltainclination and/or
      Deltaanteversion > +/- 10 degrees  (35.3%, 54/153) compared with those in the
      supine position (4.8%, 8/167; p < 0.001). A greater number of acetabular
      components were within the target zone in THAs undertaken with the patient in the
      supine position (72%, 120/167), compared with those in the lateral decubitus
      position (44%, 67/153; p < 0.001). Intraoperatively, the pelvis was more
      anteriorly tilted (p < 0.001) and more internally rotated (p = 0.04) when the
      patient was in the lateral decubitus position. CONCLUSION: The pelvic position is
      more reliable when the patient is in the supine position, leading to more
      consistent orientation of the acetabular component. Significant differences in
      pelvic tilt and rotation are seen with the patient in the lateral decubitus
      position. Cite this article: Bone Joint J 2018;100-B:1280-8.

PMID- 30295538
TI  - Intraoperative placement of total hip arthroplasty components with robotic-arm
      assisted technology correlates with postoperative implant position.
AB  - AIMS: The aim of this study was to evaluate the accuracy of implant placement
      when using robotic assistance during total hip arthroplasty (THA). PATIENTS AND
      METHODS: A total of 20 patients underwent a planned THA using preoperative CT
      scans and robotic-assisted software. There were nine men and 11 women (n = 20
      hips) with a mean age of 60.8 years (sd 6.0). Pelvic and femoral bone models were
      constructed by segmenting both preoperative and postoperative CT scan images. The
      preoperative anatomical landmarks using the robotic-assisted system were matched
      to the postoperative 3D reconstructions of the pelvis. Acetabular and femoral
      component positions as measured intraoperatively and postoperatively were
      evaluated and compared. RESULTS: The system reported accurate values for
      reconstruction of the hip when compared to those measured postoperatively using
      CT. The mean deviation from the executed overall hip length and offset were 1.6
      mm (sd 2.9) and 0.5 mm (sd 3.0), respectively. Mean combined anteversion was
      similar and correlated between intraoperative measurements and postoperative CT
      measurements (32.5 degrees , sd 5.9 degrees  versus 32.2 degrees , sd 6.4 degrees
      ; respectively; R2 = 0.65; p < 0.001). There was a significant correlation
      between mean intraoperative (40.4 degrees , sd 2.1 degrees ) acetabular component
      inclination and mean measured postoperative inclination (40.12 degrees , sd 3.0
      degrees , R2 = 0.62; p < 0.001). There was a significant correlation between mean
      intraoperative version (23.2 degrees , sd 2.3 degrees ), and postoperatively
      measured version (23.0 degrees , sd 2.4 degrees ; R2 = 0.76; p < 0.001).
      Preoperative and postoperative femoral component anteversion were significantly
      correlated with one another (R2 = 0.64; p < 0.001). Three patients had CT scan
      measurements that differed substantially from the intraoperative robotic
      measurements when evaluating stem anteversion. CONCLUSION: This is the first
      study to evaluate the success of hip reconstruction overall using robotic
      assisted THA. The overall hip reconstruction obtained in the operating theatre
      using robotic assistance accurately correlated with the postoperative component
      position assessed independently using CT based 3D modelling. Clinical correlation
      during surgery should continue to be practiced and compared with observed
      intraoperative robotic values. Cite this article: Bone Joint J 2018;100-B:1303-9.

PMID- 30295539
TI  - A randomized prospective study comparing mobile-bearing against fixed-bearing PFC
      Sigma cruciate-retaining total knee arthroplasties with ten-year minimum follow
      up.
AB  - AIMS: This study compares the PFC total knee arthroplasty (TKA) system in a
      prospective randomized control trial (RCT) of the mobile-bearing rotating
      platform (RP) TKA against the fixed-bearing (FB) TKA. This is the largest RCT
      with the longest follow-up where cruciate-retaining PFC total knee arthroplasties
      are compared in a non-bilateral TKA study. PATIENTS AND METHODS: A total of 167
      patients (190 knees with 23 bilateral cases), were recruited prospectively and
      randomly assigned, with 91 knees receiving the RP and 99 knees receiving FB. The
      mean age was 65.5 years (48 to 82), the mean body mass index (BMI) was 29.7 kg/m2
      (20 to 52) and 73 patients were female. The Knee Society Score (KSS), Knee
      Society Functional Score (KSFS), Oxford Knee Score (OKS), Western Ontario and
      McMaster Universities Arthritis Index (WOMAC), and 12-Item Short-Form Health
      Survey Physical and Mental Component Scores (SF-12 PCS, SF-12 MCS) were gathered
      and recorded preoperatively, at five-years' follow-up, and at ten years' follow
      up. Additionally, Knee Injury and Osteoarthritis Outcome Scores (KOOS) were
      collected at five- and ten-year follow-ups. The prevalence of radiolucent lines
      (RL) on radiographs and implant survival were recorded at five- and ten-year
      follow-ups. RESULTS: At the ten-year follow-up, the RP group (n = 39) had a
      statistically significant superior score in the OKS (p = 0.001), WOMAC (p =
      0.023), SF-12 PCS (p = 0.019), KOOS Activities of Daily Living (ADL) (p = 0.010),
      and KOOS Sport and Recreation (Sport/Rec) (p = 0.006) compared with the FB group
      (n = 46). The OKS, SF-12 PCS, and KOOS Sport/Rec at ten years had mean scores
      above the minimal clinically important difference (MCID) threshold. There was no
      significant difference in prevalence of radiolucency between groups at five
      years' follow-up (p = 0.449), nor at ten-years' follow-up (p = 0.08). Implant
      survival rate at 14 years postoperative was 95.2 (95% CI 90.7 to 99.8) and 94.7
      (95% CI 86.8 to 100.0) for the RP and FB TKAs, respectively. CONCLUSION: At ten
      year follow-up, the mobile-bearing knee joint arthroplasty had statistically and
      clinically relevant superior OKS, SF-12 PCS, and KOOS (Sport/Rec) than the fixed
      bearing platform. No difference was seen in prevalence of radiolucent lines.
      There was a greater than 94% implant survival rate for both cohorts at 14 years.
      Cite this article: Bone Joint J 2018;100-B:1336-44.

PMID- 30295540
TI  - Describing the Use of Animals in Animal-Assisted Intervention Research.
AB  - Currently, there has been growing attention to animal welfare in animal-assisted
      interventions (AAI). However, there is a lack of scrutiny regarding what steps to
      take to ensure animal wellbeing during AAI research. The Institutional Animal
      Care and Use Committee (IACUC) reviews, monitors, and approves all research
      involving animal subjects in order to ensure an animal's ethical and humane
      treatment. However, AAI publications rarely report IACUC approval. The purpose of
      this critical review was to determine the frequency of IACUC approval and to
      report the descriptions of animal use in AAI research publications. In the 139
      articles reviewed, 14 (10%) studies reported attaining IACUC approval; 4/139 (3%)
      reported an adverse outcome on at least one animal used in the study. The
      publications inconsistently reported the training or certification and veterinary
      care of the animals. Lacking IACUC approval in AAI studies indicates that the
      field underutilizes this method of monitoring animal health and welfare. The
      IACUC should assess, approve, and monitor research protocols involving animals
      prior to conducting every study to safeguard AAI animal welfare.

PMID- 30295541
TI  - An overview of surgical sealant devices: current approaches and future trends.
AB  - INTRODUCTION: Wound leakage is a common complication after surgical incision or
      resection. In the past, a variety of clinically-approved surgical sealant devices
      have been used as an adjunct or alternative to conventional means of tissue
      sealing. However, there is still an unmet need for a sealant that can be
      universally applied over a wide range of clinical applications. This has further
      driven the emergence of both novel liquid surgical sealant devices and active
      hemostatic sealant patches to deal with the increasing complexity of surgical
      interventions in the field of hemorrhage control and wound leakage. Areas
      covered: Emphasizing the literature from the past 5 years, this review covers the
      current offering of natural, synthetic or composite surgical sealant devices in
      liquid or patch form, their appropriate clinical indications as well as emerging
      technologies, strategies and products. Expert commentary: Recent years have been
      marked by dramatic and continuous progress towards the development of novel
      surgical sealant devices and their rigorous clinical testing. In addition, next
      generation sealant formulations such as active hemostatic sealant patches and bio
      inspired or nanoparticle-based sealant concepts have been developed and are
      constantly being evaluated and refined.

PMID- 30295542
TI  - Neurosarcoidosis As a Rare Differential Diagnosis for Single Or Multiple Lesions
      of the Nervous System.
AB  - OBJECTIVE: Sarcoidosis is a multisystemic granulomatous disease of unknown cause
      which affects the lung or bilateral hilar lymphadenopathy in over 90% of the
      cases. Neurosarcoidosis (NS) is rare and accounts for approximately 5 - 15% of
      the cases. Involvement of all parts of the central and peripheral nervous system
      is possible with various clinical symptoms, e. g. seizures, hydrocephalus,
      optic/facial nerve palsy or hearing loss. METHODS: We screened the
      neuropathological data bases and the medical records of two neurosurgical
      university hospitals for cases of NS. All these cases had been verified by
      surgical biopsy. We retrospectively evaluated the patient's records with special
      regard to the histopathology reports and specific clinical symptoms. RESULTS: We
      identified 9 cases of NS between 1994 and 2014 (3 female, 6 male patients). The
      average age at the time of diagnosis of NS was 41,4 years. Various clinical
      symptoms like hydrocephalus (n = 3), seizures (n = 1), meningitis (n = 1),
      optical nerve involvment with vision disorder (n = 1), myelitis with paraplegia
      (n = 1), mastoiditis with hearing loss (n = 1), back pain syndrome (n = 2) were
      present. 7 patients were treated with corticosteroids, 1 patient with
      cyclophosphamide and 1 with a combination of corticosteroids and methotrexate.
      CONCLUSION: NS is a rare but potentially life-threatening disease. It is
      difficult to distinguish sarcoidosis from other granulomatous diseases,
      infectious diseases like tuberculosis, multiple sclerosis or neoplasm. For a
      definite diagnosis, a neurosurgical biopsy with histological evidence of
      noncaseating epithelioid cell granulomas is required, followed by
      multidisciplinary treatment.

PMID- 30295543
TI  - Efficacy of the combination of carteolol hydrochloride + latanoprost in the
      treatment of glaucoma and ocular hypertension.
AB  - INTRODUCTION: The only evidence-based mechanism for prevention and treatment of
      glaucomatous optic neuropathy is decreasing the intraocular pressure (IOP).
      Prescribing multiple ocular hypotensive agents, such as the combination of
      carteolol and latanoprost, may synergistically improve IOP; however, doing so may
      increase the complexity of a medication regimen, in turn, impairing patient
      adherence. Fixed-combination glaucoma medications offer convenience and
      effectiveness. New to this class of glaucoma medication is fixed combination
      carteolol-latanoprost (FCCL). Area covered: This review intends to give the
      reader a better understanding of the efficacy of the combination of carteolol and
      latanoprost separately, and where FCCL fits into the vast medical arsenal of IOP
      drops. Furthermore, it outlines the particular pharmacologic mechanisms targeted,
      the pharmacokinetics, effectiveness, the advantages of fixed-combination
      administration, and tolerability. Expert opinion: The combination of carteolol
      and latanoprost, separately or in a fixed-combination, is more effective than
      either drug alone. Given the early stage in development of FCCL, it has yet to be
      determined how FCCL compares to other fixed-combination medications. However,
      pending further approval, fixed-combination carteolol-latanoprost may represent a
      reasonable alternative for a patient whose IOP is inadequately controlled on a
      prostaglandin analog alone and for whom a simplified combination is preferred.

PMID- 30295544
TI  - Structured Model of Neurorehab: A Pilot Study of Modern Multitouch Technology and
      Virtual Reality Platforms for Training Sociocognitive Deficit in Children with
      Acquired Brain Injury.
AB  - Social competence is often impaired in children with acquired brain injury (ABI),
      but evidence-based rehabilitation has remained undeveloped. This pilot-study
      aimed to create a structured model for sociocognitive rehabilitation for children
      with ABI. A total of 32 children aged 8-13 years participated: 22 with ABI 
      epilepsy, traumatic brain injury, or tic disorder and 10 healthy controls.
      Interactive computer-based applications were implemented into rehabilitation
      design using multitouch-multiuser tabletop (MMT) devices: Snowflake MultiTeach
      (MT) and Diamond Touch Table (DTT), plus MediqVR virtual reality (VR) platform.
      At baseline, patients demonstrated social incompetence compared to healthy
      controls. Post-training evaluations showed that rehabilitation on Snowflake MT
      improved children's executive and cooperation skills. DTT developed new
      communication and language skills, metacognitive skills, and coping with
      difficult social situations. This structured model for social competence
      rehabilitation helps therapists to understand the objectives and tools for
      improving social and cooperation skills in children with ABI. We provide
      practical recommendations using next-generation devices, which are effective and
      motivating for children.

PMID- 30295545
TI  - Timing and Sequence of Events: HIV Status Disclosure, Condomless Anal Sex, and
      Sexual Agreement Formation Among Same-Sex Male Couples.
AB  - Despite the implications for human immunodeficiency virus (HIV) prevention and
      sexual health, little is known about the timing and chronological order of when
      same-sex male couples disclose their HIV serostatus, establish a sexual
      agreement, and first engage in condomless anal sex (CAS) in their relationships.
      Dyadic data from 357 dyads were used to describe when these respective events
      occurred; whether members of a couple concurred about when the events happened;
      and the chronological order of these events. For many, disclosure and CAS
      happened within the first month, whereas an agreement tended to occur much later
      (if at all). Couples' concordance of when disclosure and agreement formation
      happened differed by their serostatus, whereas there was little difference by
      serostatus for CAS. The chronological order of these events revealed interesting
      patterns and varied substantially. Although two-thirds of partners reported
      disclosure had occurred first, some reported events happening on the same day.
      These findings reveal that the first few months in a same-sex male couple's
      relationship is a critical time period for when information and decisions about
      sexual health occur. Suggestions are provided for how current and future HIV
      prevention efforts could assist couples with their sexual health needs.

PMID- 30295547
TI  - Executive functions and clinical symptoms in children exposed to maltreatment.
AB  - There is evidence of an association between childhood maltreatment and lifelong
      cognitive impairment. Few studies investigate cognitive functioning in maltreated
      children. The objective of this study was to investigate whether there are
      differences in executive processing between maltreated and nonmaltreated
      children. Additionally, clinical symptoms were compared between groups and
      possible associations between clinical symptoms, and deficits in executive
      functions were investigated. The sample consisted of 55 children (8-12 years), 30
      with a history of maltreatment and 25 with no history of maltreatment. An
      interview was conducted with the child's legal guardian and instruments were
      administered: Juvenile Victimization Questionnaire (JVQ), Child Behavior
      Checklist (CBCL), and Spence Children's Anxiety Scale (SCAS). The following
      clinical instruments were administered to the children: JVQ, Trauma Symptom
      Checklist for Children (TSCC), and Children's Depression Inventory (CDI).
      Children underwent neuropsychological assessment. Data were analyzed by comparing
      the groups for clinical and cognitive variables. Differences were found between
      the groups in all executive functions. Most clinical symptomatology scales showed
      differences between the groups. Few associations were found between clinical and
      executive impairment profiles. Cognitive stimulation interventions, focused on
      inhibitory control, should be proposed in combination with psychotherapy.

PMID- 30295546
TI  - Left ventricular reverse remodeling prediction in non-ischemic cardiomyopathy:
      present and perspectives.

PMID- 30295548
TI  - Optimal medical treatment of hypertension in patients with coronary artery
      disease.
AB  - INTRODUCTION: Coronary artery disease (CAD) remains the leading cause of
      mortality and morbidity worldwide, and hypertension is its most prevalent
      modifiable risk factor. Patients with CAD and concomitant hypertension are a
      special population with distinct physiologic and structural alterations. Optimal
      blood pressure (BP) control in this population has been linked with reduction in
      adverse outcomes, however, excessive lowering of BP could jeopardize myocardial
      and cerebral perfusion. Areas covered: Authors highlight the prevalence of the
      CAD and hypertension dyad, as well as the implications of various structural and
      physiological changes in this population. Subsequently, available data on optimal
      BP targets in such patients, and lastly the J-curve phenomenon as well as
      antihypertensive agent use are discussed. Expert commentary: Current guideline
      recommendations are based on data from trials such as SPRINT and ACCORD which did
      not specifically focus on the CAD population. Based on data from observational
      studies and post hoc analyses, the best therapeutic systolic (SBP) and diastolic
      (DBP) targets may be ~ 130 mmHg and ~ 80 mmHg, respectively. Caution should be
      taken to not lower SBP below 120 mmHg and DBP below 60 mmHg.

PMID- 30295549
TI  - Evaluating exposure using confidence intervals: implication in tiered
      quantitation of metabolites for safety risks.

PMID- 30295550
TI  - Quantification of phenolic acid metabolites in humans by LC-MS: a structural and
      targeted metabolomics approach.
AB  - AIM: Co-metabolism between a human host and the gastrointestinal microbiota
      generates many small phenolic molecules such as 3-hydroxy-3-(3
      hydroxyphenyl)propanoic acid (3,3-HPHPA), which are reported to be elevated in
      schizophrenia and autism. Characterization of these chemicals, however, has been
      limited by analytic challenges. METHODOLOGY/RESULTS: We applied HPLC to separate
      and quantify over 50 analytes, including multiple structural isomers of 3,3-HPHPA
      in human cerebrospinal fluid, serum and urine. Confirmation of identity was
      provided by NMR, by MS and other detection methods. The highly selective methods
      support rapid quantification of multiple metabolites and exhibit superior
      chromatographic behavior. CONCLUSION: An improved ultra-HPLC-MS/MS and structural
      approaches can accurately quantify 3,3-HPHPA and related analytes in human
      biological matrices.

PMID- 30295551
TI  - Sensitive LC-MS/MS method for quantitation of levodopa and carbidopa in plasma:
      application to a pharmacokinetic study.
AB  - AIM: The combination of levodopa with carbidopa has been used for treatment of
      Parkinson's disease being an important therapy in dopamine level control in the
      brain. Both are very polar compounds becoming a challenge for analysis by LC
      MS/MS. MATERIALS & METHODS: In this work, it was developed and validated a
      sensitive bioanalytical method by UHPLC-MS/MS for simultaneous levodopa and
      carbidopa quantification in human plasma using a fast protein precipitation
      method. Moreover, the bioanalytical method was applied to a pharmacokinetic study
      in healthy volunteers. RESULTS/CONCLUSION: The results demonstrated a sensitive
      and adequate method for application to pharmacokinetic/bioequivalence studies.

PMID- 30295552
TI  - Percutaneous retrogasserian glycerol rhizotomy for trigeminal neuralgia: an
      alternative technique.
AB  - BACKGROUND: One of the challenges faced by the modern-day NHS is workplace
      shortages, and experienced radiographers for intra-operative neurosurgical
      imaging is one such scenario. We describe our method for Percutaneous
      Retrogasserian Glycerol Rhizotomy (PRGR) using frameless neuronavigation which
      can be used effectively in such scenarios. METHOD: Stealth neuronavigation is
      used for needle placement within the foramen ovale and injection of glycerol,
      under sedation. RESULTS: In our experience of ten procedures, it is accurate,
      safe and effective. Good results were obtained on all occasions. It can be
      repeated as often as necessary using the same Stealth(r) CT scan and reduces
      exposure for staff and patients, where repeated injections are required.
      CONCLUSION: This simple modification of PRGR technique is effective and safe
      provided the surgeon has previous experience in undertaking this procedure.

PMID- 30295553
TI  - Repeated pulmonary exposures to zinc ions enhance inflammatory responses to
      subsequent metal exposures.
AB  - AIM OF STUDY: Metal contaminants contribute to adverse human health effects via
      acute and chronic exposures. Acute metal exposures followed by prolonged
      secondary metal exposures may elicit exaggerated inflammatory responses in
      certain individuals. The aim of this study is to determine whether repeated
      pulmonary exposures to zinc chloride (ZnCl2) alter subsequent responses to zinc
      or cerium exposures. MATERIALS AND METHODS: Rats were intratracheally (IT)
      instilled with physiologic saline (n = 24) or 0.05 mg/kg ZnCl2 (n = 16) twice
      weekly for 4 weeks. Four days after last dosing, the saline group was divided
      into three subgroups, each IT-instilled with either saline, ZnCl2 or CeCl3 (both
      at 0.1 mg/kg). The ZnCl2 pre-instilled rats were divided into two subgroups, each
      instilled with 0.1 mg/kg ZnCl2 or CeCl3. Biomarkers of lung injury/inflammation
      were assessed in bronchoalveolar lavage (BAL) fluid collected 24 hours later.
      Oxidative stress was evaluated as total and reduced glutathione in BAL. RESULTS:
      Increases in inflammatory cells, LDH, albumin, leptin, MCP-1, IP-10, fractalkine,
      TNFalpha and RANTES were observed in rats instilled with multiple PBS and then
      with 0.1 mg/kg ZnCl2 and CeCl3. However, rats pre-exposed repeatedly to 0.05
      mg/kg ZnCl2 and then challenged with 0.1 mg/kg ZnCl2 or CeCl3 showed even more
      eosinophils, lymphocytes, and increased concentrations of hemoglobin and MIP
      1alpha. Significant reduction in GSH/GSSG ratios in BAL in response to all ZnCl2
      or CeCl3 exposures indicated oxidative stress. CONCLUSION: Previous exposure to
      zinc ions increases responsiveness to subsequent exposures to zinc and cerium
      ions. These findings suggest enhanced sensitization possibly due to a reduction
      in antioxidant defenses.

PMID- 30295554
TI  - Impact of baseline neurocognitive functioning on outcomes following
      rehabilitation of executive function training for veterans with history of
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) is common among Veterans, and sequelae frequently
      include deficits in attention and executive function and problems with emotional
      regulation. Although rehabilitation has been shown to be effective, it is not
      clear how patient characteristics such as baseline cognitive status may impact
      response to rehabilitation in this sample. Explore the relationship between
      baseline neuropsychological status and postintervention functional outcomes in
      Veterans with chronic TBI. Thirty-three Veterans with chronic mild-severe TBI
      completed a neuropsychological evaluation, a functional assessment of executive
      function (EF), and measures of emotional and everyday functioning pre- and post
      EF training or control training. Performance on baseline neuropsychological
      measures was used to cluster participants. Participants' performance at baseline
      and postintervention assessments was compared by cluster using multivariate
      analyses of variance (MANOVAs). Cognitive Difficulty (CD; n = 19) and Cognitively
      Normal (CN; n = 14) clusters were identified. CD was characterized by z <= -.75
      on neuropsychological measures of overall attention/EF, working memory, and
      memory. CD participants performed worse on functional EF assessment and endorsed
      more PTSD symptoms and community integration problems, at baseline. CD
      participants improved post-EF training, but not control training, on
      neuropsychological and functional measures. CN participants did not show
      statistically significant improvement. For Veterans with chronic TBI, cognitive
      assessment can aid in identifying functional impairment and assist treatment
      planning. Cognitive rehabilitation training appears to be a beneficial treatment
      option for TBI patients with cognitive, emotional, and daily living difficulties.

PMID- 30295556
TI  - Dysfunctional cerebral autoregulation is associated with delirium in critically
      ill adults.
AB  - Delirium is common during critical illness and is associated with morbidity and
      mortality, but its pathophysiology is unknown. We tested whether dysfunctional
      cerebral autoregulation (CA) contributes to the development of delirium. Adult
      patients ( n = 40) with respiratory failure and/or shock were prospectively
      enrolled. Continuous recordings of regional cerebral oxygen saturation (rSO2)
      were obtained by near-infrared spectroscopy (NIRS) during the first 72 h of
      intensive care unit (ICU) admission. CA function was estimated by the cerebral
      oximetry index (COx), which is the time-varying correlation between rSO2 and mean
      arterial pressure (MAP). Delirium was assessed daily. The median ICU stay was
      seven days (IQR 4-13). Twenty-four patients (60%) screened positive for delirium
      on at least one day during their stay. Taking positive COx values to reflect
      periods of CA dysfunction, we found that the cumulative duration of CA
      dysfunction during the first one to three days in the ICU was significantly
      associated with the subsequent development of delirium. Additionally, we assessed
      two alternative methods for estimating optimal MAP targets in individual
      patients. In summary, early disturbances in CA may contribute to delirium, and
      NIRS-derived rSO2 may be used to identify individual perfusion targets in
      critically ill patients.

PMID- 30295555
TI  - Development and reliability of the Prospective Memory Assessment for Children &
      Youth (PROMACY): A preliminary study in a nonclinical sample.
AB  - Prospective memory (PM), "remembering to remember," has been linked to important
      functional outcomes in adults. Studies of PM in children and adolescents would
      benefit from the development and validation of developmentally appropriate
      clinical measures with known psychometric properties. The Prospective Memory
      Assessment for Children & Youth (PROMACY), a performance-based measure of PM, was
      developed for the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol,
      Memory and Executive Functioning Substudy, and includes Summary, Time-, and Event
      based scores derived from eight trials with an ongoing word search task. Fifty
      four healthy perinatally HIV-exposed, uninfected children and youth, mean age 13
      years, 54% female, 76% Black/non-Hispanic, and 61% impoverished were included in
      this psychometric analysis. PROMACY Summary Scores demonstrated low, but broadly
      acceptable internal consistency as measured by Cronbach's alpha and Spearman
      Brown. Better PROMACY performance was associated with older age, but no other
      demographic factors. Generally medium-sized correlations were observed between
      the PROMACY Summary Score and standard clinical measures of retrospective memory,
      working memory, executive functions, and IQ. Findings from this preliminary
      psychometric study of nonclinical children and youth provide cautious support for
      the internal consistency and construct validity of PROMACY's Summary Score that
      awaits replication and extension in larger samples of healthy children, youth and
      clinical populations.

PMID- 30295557
TI  - Fasting and postprandial serum bile acids after RYGB surgery.

PMID- 30295558
TI  - Small vessel disease is associated with altered cerebrovascular pulsatility but
      not resting cerebral blood flow.
AB  - Cerebral small vessel disease (SVD) contributes to 25% of ischemic strokes and
      45% of dementias. We aimed to investigate the role of cerebral blood flow (CBF)
      and intracranial pulsatility in SVD. We scanned 60 patients with minor ischemic
      stroke, representing a range of white matter hyperintensities (WMH). We rated WMH
      and perivascular spaces (PVS) using semi-quantitative scales and measured WMH
      volume. We measured flow and pulsatility in the main cerebral vessels and
      cerebrospinal fluid (CSF) using phase-contrast MRI. We investigated the
      association between flow, pulsatility and SVD features. In 56/60 patients (40
      male, 67.8+/-8.3 years) with complete data, median WMH volume was 10.7 mL (range
      1.4-75.0 mL), representing median 0.77% (0.11-5.17%) of intracranial volume.
      Greater pulsatility index (PI) in venous sinuses was associated with larger WMH
      volume (e.g. superior sagittal sinus, beta = 1.29, P < 0.01) and more basal
      ganglia PVS (e.g. odds ratio = 1.38, 95% confidence interval 1.06, 1.79, per 0.1
      increase in superior sagittal sinus PI) independently of age, sex and blood
      pressure. CSF pulsatility and CBF were not associated with SVD features. Our
      results support a close association of SVD features with increased intracranial
      pulsatility rather than with low global CBF, and provide potential targets for
      mechanistic research, treatment and prevention of SVD.

PMID- 30295559
TI  - Losing silence, gaining acceptance: a qualitative exploration of the role of
      thoughts in adult patients with subjective tinnitus.
AB  - OBJECTIVE: Tinnitus is one of the most common somatic symptoms to affect
      humanity. Prevalence rates in adult populations range from 8.2 to 20.1%. Our aim
      was to understand the beliefs and interpretations of tinnitus and the experience
      of living with it. DESIGN: An in depth grounded theory interview study. Grounded
      theory is an inductive approach to developing theory. SAMPLE: Thirteen
      contrasting people with tinnitus who had sought help from clinical services in
      England. RESULTS: We identified that the thinking patterns that people held
      around their tinnitus impacted how they experienced it. A core category emerged
      from the data, "sense making". Around "sense making" eight other themes operated.
      Results are discussed in relation to the literature on tinnitus acceptance and
      beliefs. CONCLUSIONS: The aim of interventions is to foster understanding and
      enhance perceptions of control, which may minimise the emotional impact of
      tinnitus and reduce the perceived severity of consequences.

PMID- 30295560
TI  - Hypertension, dietary salt and cognitive impairment.
AB  - Dementia is growing at an alarming rate worldwide. Although Alzheimer disease is
      the leading cause, over 50% of individuals diagnosed with Alzheimer disease have
      vascular lesions at autopsy. There has been an increasing appreciation of the
      pathogenic role of vascular risk factors in cognitive impairment caused by
      neurodegeneration. Midlife hypertension is a leading risk factor for late-life
      dementia. Hypertension alters cerebrovascular structure, impairs the major
      factors regulating the cerebral microcirculation, and promotes Alzheimer
      pathology. Experimental studies have identified brain perivascular macrophages as
      the major free radical source mediating neurovascular dysfunction of
      hypertension. Recent evidence indicates that high dietary salt may also induce
      cognitive impairment. Contrary to previous belief, the effect is not necessarily
      associated with hypertension and is mediated by a deficit in endothelial nitric
      oxide. Collectively, the evidence suggests a remarkable cellular diversity of the
      impact of vascular risk factors on the cerebral vasculature and cognition.
      Whereas long-term longitudinal epidemiological studies are needed to resolve the
      temporal relationships between vascular risk factors and cognitive dysfunction,
      single-cell molecular studies of the vasculature in animal models will provide a
      fuller mechanistic understanding. This knowledge is critical for developing new
      preventive, diagnostic, and therapeutic approaches for these devastating diseases
      of the mind.

PMID- 30295561
TI  - Long-term health benefits of stroke prevention with apixaban versus vitamin K
      antagonist warfarin in patients with non-valvular atrial fibrillation in Germany:
      a population-based modelling study.
AB  - BACKGROUND: Patients with non-valvular atrial fibrillation (NVAF) have a five
      times higher stroke risk. For more than 50 years, vitamin K antagonists (VKAs)
      have been the primary medication for stroke prevention. Apixaban, a non-vitamin K
      oral anticoagulant (NOAC), has demonstrated better efficacy and safety
      characteristics than the VKA warfarin in the ARISTOTLE trial. This study aims to
      quantify the potential societal effects of using apixaban instead of VKA in the
      German NVAF population from 2017 to 2030. METHODS: Using an existing Markov model
      and a dynamic population approach, we modelled the health benefits of apixaban in
      patients with NVAF compared to VKA therapy in the German population from 2017 to
      2030. RESULTS: The results represent the extrapolated direct long-term health
      benefits of apixaban over VKA therapy for the German NVAF population. From 2017
      until 2030, the use of apixaban instead of a VKA could avoid 52,185 major
      clinical events. This includes 15,383 non-fatal strokes or SEs, 22,483 non-fatal
      major bleeds, and 14,319 all-cause deaths, which correspond to 109,887 life years
      gained. CONCLUSION: This study demonstrated that using apixaban instead of VKA
      for stroke prevention can lead to considerable reduction in cardiovascular
      events.

PMID- 30295562
TI  - Chimpanzee Cooperation Is Fast and Independent From Self-Control.
AB  - Large-scale cooperation is a hallmark of our species and appears to be unique
      among primates. Yet the evolutionary mechanisms that drove the emergence of
      humanlike patterns of cooperation remain unclear. Studying the cognitive
      processes underlying cooperative behavior in apes, our closest living relatives,
      can help identify these mechanisms. Accordingly, we employed a novel test battery
      to assess the willingness of 40 chimpanzees to donate resources, instrumentally
      help others, and punish a culpable thief. We found that chimpanzees were faster
      to make prosocial than selfish choices and that more prosocial individuals made
      the fastest responses. Further, two measures of self-control did not predict
      variation in prosocial responding, and individual performance across cooperative
      tasks did not covary. These results show that chimpanzees and humans share key
      cognitive processes for cooperation, despite differences in the scope of their
      cooperative behaviors.

PMID- 30295563
TI  - Where there is inflammation, treatment may reduce disability progression - Yes.

PMID- 30295564
TI  - Meta-Analysis of the Effects of QoI and DMI Fungicide Combinations on Fusarium
      Head Blight and Deoxynivalenol in Wheat.
AB  - Field trials were conducted in 17 U.S. states to evaluate the effects of quinone
      outside inhibitor (QoI) and demethylation inhibitor (DMI) fungicide programs on
      Fusarium head blight index (IND) and deoxynivalenol (DON) toxin in wheat. Four
      DMI-only treatments applied at Feekes 10.5.1, five QoI-only treatments applied
      between Feekes 9 or Feekes 10.5, three QoI+DMI mixtures applied at Feekes 10.5,
      and three treatments consisting of a QoI at Feekes 9 followed by a DMI at Feekes
      10.5.1 were evaluated. Network meta-analytical models were fitted to log
      transformed mean IND and DON data and estimated contrasts of log means were used
      to obtain estimates of mean percent controls relative to the nontreated check as
      measures of efficacy. Results from the meta-analyses were also used to assess the
      risk of DON increase in future trials. DMI at Feekes 10.5.1 were the most
      effective programs against IND and DON and the least likely to increase DON in
      future trials. QoI-only programs increased mean DON over the nontreated checks
      and were the most likely to do so in future trials, particularly when applied at
      Feekes 10.5. The effects of QoI+DMI combinations depended on the active
      ingredients and whether the two were applied as a mixture at heading or
      sequentially. Following a Feekes 9 QoI application with a Feekes 10.5.1
      application of a DMI reduced the negative effect of the QoI on DON but was not
      sufficient to achieve the efficacy of the Feekes 10.5.1 DMI-only treatments. Our
      results suggest that one must be prudent when using QoI treatments under moderate
      to high risk of FHB, particularly where the QoI is used without an effective DMI
      applied in combination or in sequence.

PMID- 30295565
TI  - Where there is inflammation, treatment may reduce disability progression - No.

PMID- 30295566
TI  - Clinical effectiveness of osteoporosis treatment in older patients: A fracture
      liaison service-based prospective study.
AB  - The clinical efficacy of anti-osteoporotic treatments in old patients is
      discussed. The aim of this study was to assess if the use of anti-osteoporotic
      treatments for the secondary prevention of osteoporotic fractures could reduce
      the risk of refractures in patients over 75 years old in a Fracture Liaison
      Service. In this population of frail, elderly patients presenting with a recent
      osteoporotic fracture, we observed that the refracture incidence was similar in
      the treated group and the untreated group during the first year. However, 30
      months after the index fracture, the osteoporosis medication for a year or more
      reduced the incidence of refractures by 70%.

PMID- 30295568
TI  - Lessons from filial piety: A social-life-span approach to building the connection
      that survives death.
AB  - The purpose of this article is to unpack concepts surrounding "the connection
      that survives death" between living people and the deceased. The study was
      designed as the qualitative arm of an integrated project on filial piety in
      contemporary times, and data were collected from 17 interviews with Korean human
      service professionals from Australia, New Zealand and Korea. The findings from
      the study indicate that the connectedness with the dead is an important part of
      the participants' mental and social lives, and this postmortem relationship can
      be embodied through practising "memorial piety" and "memorial work".

PMID- 30295567
TI  - The self-reported perceptions of the repercussions of the disease and its
      treatments on daily life for young women with breast cancer and their partners.
AB  - PURPOSE: This study aimed to compare the self-reported perceptions of the
      repercussions of the disease and its treatments and emotional distress in young
      women with breast cancer and their partners. DESIGN: Cross-sectional study using
      self-reported questionnaires. SAMPLE: 491 couples in which women were aged <45
      years when diagnosed with non-metastatic breast cancer in four different groups
      of treatment: during chemotherapy with or without Trastuzumab; under Trastuzumab
      with or without hormone therapy; during hormone therapy; and during the follow-up
      period. METHODS: Patients and partners completed a questionnaire assessing their
      self-reported perceptions of the disease and treatments (Patient YW-BCI and
      Partner YW-BCI for the partners) and their emotional distress (CESD; STAI).
      FINDINGS: Patients reported more difficulties than partners in the management of
      child(ren) and everyday life, body image and sexuality, negative affectivity
      about the disease and apprehension about the future, career management, and
      finances. While the difficulties were generally more marked in the chemotherapy
      and Trastuzumab groups than in the hormone therapy and follow-up groups, the
      negative affectivity about the disease and apprehension about the future was high
      in all four groups, especially in patients. The partners reported more
      difficulties in sharing with close relatives, and even more in those groups
      reflecting the latest treatment phases. No difference appeared between patients
      and partners in couple cohesion and deterioration of relationships with
      relatives. Partners were less anxious than patients but as depressed as them.
      CONCLUSIONS: Difficulties of patients and partners seem particularly severe in
      the early care pathway, maybe reflecting better adjustment in women under
      surveillance and their partners. A longitudinal study will substantiate this
      finding and enable a better identification of some explanatory processes of these
      differences and similarities in the daily self-reported repercussions of the
      disease throughout the cancer care pathway. Implications for psychosocial
      oncology: It seems important to support young women with breast cancer and their
      partners, as our results evidence distress in both and differences according to
      the type of treatment the woman is currently receiving. Healthcare providers need
      consistent methods to identify and respond to couples' distress and reduce
      significant disparities in support.

PMID- 30295569
TI  - The Power of Attention: Using Eye Gaze to Predict Other-Regarding and Moral
      Choices.
AB  - According to research studying the processes underlying decisions, a two-channel
      mechanism connects attention and choices: top-down and bottom-up processes. To
      identify the magnitude of each channel, we exogenously varied information intake
      by systematically interrupting participants' decision processes in Study 1 ( N =
      116). Results showed that participants were more likely to choose a predetermined
      target option. Because selection effects limited the interpretation of the
      results, we used a sequential-presentation paradigm in Study 2 (preregistered, N
      = 100). To partial out bottom-up effects of attention on choices, in particular,
      we presented alternatives by mirroring the gaze patterns of autonomous decision
      makers. Results revealed that final fixations successfully predicted choices when
      experimentally manipulated (bottom up). Specifically, up to 11.32% of the link
      between attention and choices is driven by exogenously guided attention (1.19%
      change in choices overall), while the remaining variance is explained by top-down
      preference formation.

PMID- 30295570
TI  - Head Transplantation: The Immune System, Phantom Sensations, and the Integrated
      Mind.
AB  - The principal focus of this paper is to consider the implications of head and
      neck transplantation surgery on the issue of personal identity. To this end, it
      is noted that the immune system has not only been established to impose a level
      of self-identity on bodily cells, it has also been implicated in mental
      development and the regulation of mental state. In this it serves as a paradigm
      for the mind as the product of cephalic and extracephalic systems. The importance
      of bodily systems in identity is then discussed in relation to phantom tissue
      syndrome. The data strongly indicate that, even if surgically successful, head
      and neck transplantation will result in the loss of the continuity of personal
      identity.

PMID- 30295571
TI  - Performance shaping factors in the human error probability modification of human
      reliability analysis.
AB  - Human-induced accidents indicate the importance of human reliability analysis
      (HRA) in reducing and eliminating human errors, thus improving the reliability of
      human-machine systems. HRA takes both qualitative and quantitative approaches to
      determine the error of the operators and the contexts in which tasks are
      performed. To ensure that HRA results can objectively evaluate human error
      behaviors, the quantification of human error probability (HEP) is typically based
      on the qualitative analysis of human factors and task contexts and is further
      refined by performance shaping factors (PSFs). A good HEP process development
      includes the selection of PSFs, the evaluation of PSFs and the quantification
      strategy of HEP. A variety of HEP quantification analyses based on PSFs has been
      widely adopted in contemporary HRA studies. This work reviews three major
      quantification strategies used in HRA methods. Additionally, we generalize the
      modification of HEP with PSFs into a paradigm.

PMID- 30295573
TI  - Where there is inflammation, treatment may reduce disability progression -
      Commentary.

PMID- 30295572
TI  - Do Metabolic Traits, Vulnerability to Angling, or Capture Method Explain Boldness
      Variation in Eurasian Perch?
AB  - The pace-of-life syndrome (POLS) concept predicts that individuals with high
      baseline metabolic rates demonstrate high boldness, aggressiveness, and activity,
      especially in food acquisition, with associated relatively greater energy
      requirements. In fishes, these behaviors may increase individual vulnerability to
      angling. To test the predictions of the POLS concept, we quantified individual
      standard metabolic rate (SMR) and boldness in both wild-caught and hatchery
      reared Eurasian perch (Perca fluviatilis). We found both SMR and boldness to be
      repeatable traits but detected no correlation between them. Individual
      vulnerability to angling was assessed in the hatchery-reared perch, but we found
      no difference in boldness or SMR between vulnerable and nonvulnerable perch. Wild
      caught perch were ice fished using either natural or artificial bait, and we
      observed no differences in boldness or SMR with respect to bait type or capture
      order. Our findings do not support the predictions of the POLS concept and,
      consistent with earlier studies in perch, suggest that angling may not drive
      selection against boldness in this species.

PMID- 30295578
TI  - Instrument development, diverse evaluation, and furthering interprofessional
      research globally.

PMID- 30295579
TI  - A Dihydroflavonol-4-reductase-like Protein Interacts with NFR5 and Regulates
      Rhizobial Infection in Lotus japonicus.
AB  - In almost all symbiotic interactions between rhizobia and leguminous plants, host
      flavonoid-induced synthesis of Nod factors in rhizobia is required to initiate
      symbiotic response in plants. In this study, we found that Lotus japonicus Nod
      Factor Receptor 5 (LjNFR5) might directly regulate flavonoid biosynthesis during
      symbiotic interaction with rhizobia. A yeast two-hybrid analysis revealed that a
      dihydroflavonol-4-reductase-like protein (LjDFL1) interacts with LjNFR5. The
      interaction between MtDFL1 and MtNFP, two Medicago truncatula proteins with
      homology to LjDFL1 and LjNFR5, respectively, was also shown, suggesting that
      interaction between these two proteins might be conserved in different legumes.
      LjDFL1 was highly expressed in root hairs and the epidermal cells of root tips.
      Lotus ljdfl1 mutants and Medicago mtdfl1 mutants produced significantly fewer
      infection threads (ITs) than the wild-type control plants following rhizobial
      treatment. Furthermore, the roots of stable transgenic L. japonicus plants
      overexpressing LjDFL1 formed more ITs than control roots after exposure to
      rhizobia. These data indicated that LjDFL1 is a positive regulator of symbiotic
      signaling. However, the expression of LjDFL1 was suppressed by rhizobial
      treatment, suggesting that a negative feedback loop might be involved in
      regulation of the symbiotic response in L. japonicus.

PMID- 30295580
TI  - Subfamily-Specific Specialization of RGH1/MLA Immune Receptors in Wild Barley.
AB  - The barley disease resistance (R) gene locus mildew locus A (Mla) provides
      isolate-specific resistance against the powdery mildew fungus Blumeria graminis
      hordei and has been introgressed into modern cultivars from diverse germplasms,
      including the wild relative Hordeum spontaneum. Known Mla disease resistance
      specificities to B. graminis hordei appear to encode allelic variants of the R
      gene homolog 1 (RGH1) family of nucleotide-binding domain and leucine-rich repeat
      (NLR) proteins. Here, we sequenced and assembled the transcriptomes of 50 H.
      spontaneum accessions representing nine populations distributed throughout the
      Fertile Crescent. The assembled Mla transcripts exhibited rich sequence
      diversity, linked neither to geographic origin nor population structure, and
      could be grouped into two similar-sized subfamilies based on two major N-terminal
      coiled-coil (CC) signaling domains that are both capable of eliciting cell death.
      The presence of positively selected sites located mainly in the C-terminal
      leucine-rich repeats of both MLA subfamilies, together with the fact that both CC
      signaling domains mediate cell death, implies that the two subfamilies are
      actively maintained in the population. Unexpectedly, known MLA receptor variants
      that confer B. graminis hordei resistance belong exclusively to one subfamily.
      Thus, signaling domain divergence, potentially as adaptation to distinct pathogen
      populations, is an evolutionary signature of functional diversification of an
      immune receptor. [Formula: see text] Copyright (c) 2018 The Author(s). This is an
      open access article distributed under the CC BY-NC-ND 4.0 International license .

PMID- 30295582
TI  - Black Ethnicity is Not a Risk Factor for Mortality or Graft Loss After Kidney
      Transplant in the United Kingdom.
AB  - OBJECTIVES: There are conflicting reports in the literature regarding outcomes
      after kidney transplant for patients of black ethnicity. To investigate further,
      we compared outcomes for black versus white kidney transplant recipients in a
      single UK transplant center. MATERIALS AND METHODS: We analyzed 1066 kidney
      transplant recipients (80 black patients, 986 white patients) within a single
      center cohort (2007-2017) in the United Kingdom, with cumulative 4446 patient
      year follow-up. Data were electronically extracted from the Department of Health
      Informatics database for every study recruit, with manual data linkage to the UK
      Transplant Registry (for graft survival, delayed graft function, and rejection
      data) and Office for National Statistics (for mortality data). Primary outcomes
      of interest were graft/patient survival. RESULTS: Black recipients have increased
      baseline risk profiles with longer wait times, difficulty in matching, worse HLA
      matching, more socioeconomic deprivation, and lower rates of living kidney
      donors. Postoperatively, black versus white recipients had increased risk for
      delayed graft function (34.3% vs 10.2%; P < .001), increased 1-year rejection
      (16.7% vs 7.3%; P = .012), higher 1-year creatinine levels (166 vs 138 mmol/L; P
      = .003), and longer posttransplant length of stay (14.5 vs 9.5 days; P = .020).
      Although black recipients did not have increased risk of death versus white
      recipients (10.0% vs 11.0%, respectively; P = .486), they did have increased risk
      for death-censored graft loss (23.8% vs 11.1%; P = .002). However, in an adjusted
      Cox regression model, black ethnicity was not associated with increased risk for
      death-censored graft loss (hazard ratio of 1.209, 95% confidence interval, 0.660
      2.216; P = .539). CONCLUSIONS: Black kidney transplant recipients in the United
      Kingdom have increased risk of adverse graft-related outcomes due to high-risk
      baseline variables rather than their black ethnicity per se.

PMID- 30295581
TI  - The host stomatal density determines resistance to Septoria gentianae in Japanese
      gentian.
AB  - Plant stomata represent the main battlefield for host plants and the pathogens
      that enter plant tissues via stomata. Septoria spp., a group of ascomycete fungi,
      use host plant stomata for invasion and cause serious damage to agricultural
      plants. There is no evidence, however, showing the involvement of stomata in
      defense systems against Septoria infection. In this study, we isolated S.
      gentianae 20-35 (Sg20-35) from Gentiana triflora (G. triflora) showing gentian
      leaf blight disease symptoms in the field. Establishment of an infection system
      using gentian plants cultured in vitro enabled us to observe the Sg20-35
      infection process and estimate its virulence in several gentian cultivars/lines.
      Sg20-35 also entered gentian tissues via stomata and showed increased virulence
      in G. triflora compared with G. scabra and their interspecific hybrid. Notably,
      the susceptibility of gentian cultivars to Sg20-35 was associated with their
      stomatal density on the adaxial but not abaxial leaf surface. Treatment of
      EPIDERMAL PATTERNING FACTOR 9 (EPFL9/STOMAGEN) peptides, a small secreted peptide
      controlling stomatal density in Arabidopsis thaliana, increased stomatal density
      on the adaxial side of gentian leaves as well. Consequently, treated plants
      showed enhanced susceptibility to Sg20-35. These results indicate that stomatal
      density on the adaxial leaf surface is one of the major factors determining the
      susceptibility of gentian cultivars to S. gentianae and suggest that stomatal
      density control may represent an effective strategy to confer Septoria
      resistance.

PMID- 30295583
TI  - Upper Extremity Compartment Syndrome Following Radial Artery Puncture in a
      Patient Undergoing Orthotopic Liver Transplant.
AB  - Acute compartment syndrome is the physiologic consequence of increasing pressures
      within an enclosed anatomic space; if left untreated, it can subsequently cause
      irreversible necrosis, nerve injury, and tissue damage. A number of iatrogenic
      causes have been reported in the literature; however, to the best of our
      knowledge, there are no prior reports of upper extremity compartment syndrome in
      orthotopic liver transplant following arterial line placement. Here, we report a
      52-year-old male with a history of end-stage liver disease secondary to primary
      sclerosing cholangitis who presented for orthotopic liver transplant. A radial
      arterial line with 20-gauge catheter was placed atraumatically without
      complication. Intraoperatively, the patient developed severe coagulopathy. The
      cause was likely multifactorial, including dilution of factors from the massive
      blood loss during the dissection phase, a prolonged anhepatic period, and delayed
      graft function, resulting in decreased production of coagulation factors. This
      consumptive process likely subjected minor vascular injury to potential bleeding
      and caused a slow cumulative bleed into the right forearm, resulting in
      compartment syndrome. This case exemplifies the complications that can occur from
      arterial line placement in a liver transplant recipient who develops severe
      intraoperative coagulopathy. This can arguably be extrapolated to any situation
      caused by significant dilutional coagulopathy or a consumptive process, such as
      disseminated intravascular coagulation. As such, when large-volume blood
      transfusions are anticipated, we recommend that all central venous and arterial
      accesses be obtained under ultrasonographic guidance and that frequent extremity
      physical examinations should be performed at a minimum of every hour. Correcting
      the underlying coagulopathy is imperative to resolve ongoing bleeding, a high
      index of suspicion is warranted, and immediate diagnosis and therapy are integral
      to improving patient outcomes.

PMID- 30295584
TI  - Impact of Transplant Nephrectomy for Patient Survival Over the Past 15 Years: A
      Single-Center Study.
AB  - OBJECTIVES: How transplant nephrectomy affects patient survival after return to
      dialysis is unclear. Here, we compared patient survival after graft loss between
      patients with and without transplant nephrectomy. MATERIALS AND METHODS: We
      divided 171 patients who received transplant between 2000 and 2015 and had graft
      loss into 3 groups: 64 had graft failure left in situ (without nephrectomy), 51
      had nephrectomy < 3 months posttransplant (early nephrectomy), and 56 patients
      had nephrectomy > 3 months posttransplant (late nephrectomy). The primary
      endpoint was patient survival. Risk factors for patient death were also analyzed.
      Secondary endpoints included relisting for transplant and immunosuppressive agent
      status. RESULTS: Patient survival rates at 1, 3, and 5 years posttransplant in
      those without nephrectomy, early nephrectomy, and late nephrectomy were 92.1%
      /90.5%/86.6%, 96.0%/89.7%/80.4%, and 100.0% /97.9%/ 95.6%, respectively. Rates in
      patients with early nephrectomy differed significantly from those with late
      nephrectomy (P = .005). On multivariate analysis, patient survival was affected
      by relisting for transplant (hazard ratio 0.17; 95% confidence interval, 0.06
      0.41; P < .001) and graft survival duration (hazard ratio 0.36, 95% confidence
      interval, 0.13-0.93; P = .036). Relisting for transplant occurred in 46.9% of
      patients without nephrectomy, 56.9% of patients with early nephrectomy, and 51.8%
      of patients with late nephrectomy. Those with late nephrectomy took 14.7 months
      after graft loss to relist for transplant, with 7.8 months for those without
      nephrectomy (P = .039) and 6.3 months for those with early nephrectomy (P =
      .051). Only 10.9% of those without nephrectomy were immunosuppressive free, which
      was in contrast to 94.1% and 78.6% of those with early and late nephrectomy,
      respectively. CONCLUSIONS: After graft failure, patients without nephrectomy did
      not have inferior survival versus patients who received early or late
      nephrectomy. Graft survival time and relisting for transplant were associated
      with patient survival regardless of having transplant nephrectomy.

PMID- 30295585
TI  - Use of Rotational Thromboelastometry in Liver Transplantation Is Associated With
      Reduced Transfusion Requirements.
AB  - OBJECTIVES: Increased transfusion requirements in liver transplantation have been
      reported to be associated with worsened outcomes, more frequent reinterventions,
      and higher expenses. Anesthesiologists might counteract this through improved
      coagulation management. We evaluated the effects of rotational thromboelastometry
      on transfusion and coagulation product requirements and on outcome measurements.
      MATERIALS AND METHODS: Patients who were 14 years or older and who were
      undergoing liver transplant at Hannover Medical School between January 2005 and
      December 2009 were included in this retrospective analysis. Demographic,
      clinical, and laboratory data, use of rotational thromboelastometry,
      intraoperative need for blood or coagulation products and antifibrinolytic
      substances, and clinical course were recorded. Correlations were examined using
      appropriate statistical tests. RESULTS: Our study included 413 patients. Use of
      rotational thromboelastometry was associated with less frequent intraoperative
      administration of red blood cell concentrates, fresh frozen plasma, platelet
      concentrates, prothrombin complex concentrates, and antithrombin concentrates
      (all P < .05). In addition, univariate and multivariate tests showed that
      rotational thromboelastometry was correlated with decreased need for red blood
      cell concentrates and fresh frozen plasma (all P < .05). Intraoperative
      administration rates of antifibrinolytic substances and fibrinogen concentrate
      were significantly increased in patients who received rotational
      thromboelastometry monitoring (both P < .05). However, use of rotational
      thromboelastometry was not associated with massive transfusion rates (> 10 units
      vs less), clinical outcome, or length of stay in the intensive care unit (all P >
      .05). CONCLUSIONS: Use of rotational thromboelastometry during liver transplant
      may reduce the need for intraoperative transfusion and coagulation products.
      Relevant effects of rotational thromboelastometry on patient outcomes or lengths
      of stay in the intensive care unit could not be ascertained. However,
      readjustment of therapeutic thresholds may improve the clinical impact.

PMID- 30295586
TI  - Incidence of Post-Liver Transplant Hepatic Dysfunction After Sustained Virologic
      Response Following Direct-Acting Anti-Hepatitis C Therapy.
AB  - OBJECTIVES: Newly developed, direct-acting antiviral therapy is effective in over
      90% of cases to eradicate hepatitis C virus infection. Direct-acting antiviral
      therapy is also effective in liver transplant recipients with recurrent hepatitis
      C virus infection. However, hepatic function after sustained virologic response
      in transplant recipients is unknown. Here, we aimed to uncover the incidence of
      hepatic dysfunction in this patient group at our center. MATERIALS AND METHODS:
      Our study included 40 consecutive (January 2014 to February 2016) and compliant
      posttransplant recipients who achieved sustained viral response from direct
      acting antiviral therapy. Patients were investigated for incidence and causes of
      hepatic dysfunction. RESULTS: In our patient group, 4 (10%) experienced hepatic
      dysfunction with stable baseline immunosuppression, with 2 having drastic
      increases in alanine aminotransferase at 15 and 32 weeks after direct-acting
      antiviral therapy. Biopsies showed hepatitis, and both patients were treated with
      hydrocortisone, which increased their baseline immunosuppression. The 3rd patient
      had an increase in bilirubin at 21 weeks posttherapy, with biopsy showing
      macrovascular steatosis. The 4th patient had a rapid increase in bilirubin at 7
      weeks after direct-acting antiviral therapy, with biopsy showing significant duct
      loss. CONCLUSIONS: During the study period, 10% of patients experienced hepatic
      dysfunction after sustained viral response. Presumed causative factors included
      partial immune reconstitution and nonalcoholic fatty liver disease.

PMID- 30295587
TI  - A Single-Center Experience With Hematopoietic Stem Cell Transplantation for
      Pediatric Acute Lymphoblastic Leukemia: A Modest Pitch for Non-Total Body
      Irradiation Conditioning Regimens.
AB  - OBJECTIVES: Allogeneic hematopoietic stem cell transplantation has been used for
      several decades to treat patients with acute lymphoblastic leukemia. Total body
      irradiation has been promoted as an important component of conditioning regimens
      for this process; however, recent reports of chemotherapy-based conditioning
      regimens have shown comparable outcomes. MATERIALS AND METHODS: We report our
      experience with radiation-free conditioning using busulfan and cyclophosphamide
      in 127 pediatric patients with acute lymphoblastic leukemia who were treated
      between 1997 and 2014. The median age was 11 years (range, < 1 to 15 y), 70% of
      patients were male, 81.1% received transplants from HLA-matched siblings, 83%
      received peripheral blood stem cells, 41% were in second complete remission at
      the time of transplant, and 83% had B-lineage immunophenotype. RESULTS: In
      patients who were in complete remission at the time of transplant, 5-year overall
      survival, leukemia-free survival, and relapse rates were 62.48% (95% confidence
      interval, 52.29-71.09%), 49.43% (95% confidence interval, 39.57-58.53%), and
      45.64% (95% confidence interval, 35.85-54.88%), respectively. We observed
      significant differences between outcomes in patients by time of transplant,
      presence of chronic graft-versus-host disease, and remission status. CONCLUSIONS:
      Our relapse rates were comparable to those shown in recent studies, although the
      transplant-related mortality rate was lower. The results of our study showed that
      a busulfan/cyclophosphamide conditioning regimen has acceptable outcomes without
      the undesirable adverse effects of total body irradiation, particularly in
      pediatric patients. Large multicenter studies are needed to assess less toxic
      conditioning regimens with fewer adverse effects in these patients.

PMID- 30295588
TI  - N-Acetylcysteine and Benfotiamine Protect Autotransplanted Ovarian Tissue From
      Ischemia-Reperfusion Injury: An Experimental Study.
AB  - OBJECTIVES: This study aimed to compare the effects of N-acetylcysteine and
      benfotiamine in protection of ovarian tissue from ischemia caused by slow
      neovascularization injury due to intraperitoneal ovarian autotransplant in rats.
      MATERIALS AND METHODS: Twenty-eight female rats were divided into 4 groups, each
      containing 7 rats. Group 1 only had the abdomen opened and closed, group 2 was
      the transplant-only group, group 3 received benfotiamine for 3 weeks starting 1
      day before the transplant procedure, and group 4 received N-acetylcysteine for 3
      weeks starting 1 day before the transplant procedure. At the end of the
      experimental period, malondialdehyde levels in ovarian tissues together with the
      apoptosis and fibrosis, proliferating cell nuclear antigen and vascular
      endothelial growth factor immunoreactivity, and ovarian reserves were
      investigated. RESULTS: Apoptosis was significantly increased in group 2 animals.
      Primordial follicle count was higher in groups 3 and 4 than in group 2. Vascular
      endothelial growth factor immunoreactivity was decreased in groups 3 and 4
      compared with group 2. Proliferating cell nuclear antigen immunoreactivity was
      reduced in the secondary follicles in all transplant groups. CONCLUSIONS: In
      autologous intraperitoneal ovarian transplant, both benfotiamine and N
      acetylcysteine are equal and effective agents in protection of ovarian tissue
      against ischemic injury.

PMID- 30295589
TI  - Association Between Sarcopenia and Functional Status in Liver Transplant
      Patients.
AB  - OBJECTIVES: A growing body of evidence shows that frailty and functional
      performance predict liver transplant outcomes. The Organ Procurement and
      Transplant Network uses the Karnofsky Performance Status scale to adjust for
      transplant center case mix in assessing quality measures. This study explores the
      strength of the relationship between Karnofsky Performance Status scores and
      objective measures of frailty. MATERIALS AND METHODS: This observational study
      includes 136 adult, first-time liver transplant recipients at UMass Memorial
      (2006-2015) who had 2 abdominal computed tomography scans available (at <= 90
      days pretransplant and >= 7 days before that). We analyzed the relationship
      between Karnofsky Performance Status and muscle wasting using absolute and change
      in psoas muscle size and quality pretransplant. RESULTS: The mean age was 55
      years, mean Model for End-Stage Liver Disease was 22, and 34% of patients were
      women. In the study group, 50% of patients had sarcopenia pretransplant and 71.3%
      demonstrated declined lean psoas area at an average rate of 11% per month.
      Patients who experienced muscle wasting at a rate of >= 1% per month had 2.83
      times the risk (95% confidence interval, 1.18-6.80) of being severely
      impaired/disabled pretransplant. The risk increased by 2.32-fold (95% confidence
      interval, 1.44-3.75) for every standard deviation decrease in pretransplant lean
      psoas area. CONCLUSIONS: Provider-assessed physical health status moderately
      correlates with objective measures of frailty.

PMID- 30295590
TI  - Effects of a reminder to initiate oral anticoagulation in patients with atrial
      fibrillation/atrial flutter discharged from the emergency department: REMINDER
      study.
AB  - CLINICIAN'S CAPSULE What is known about the topic? Oral anticoagulation (OAC)
      reduces stroke risk in patients with atrial fibrillation or flutter; however,
      initiation rates in patients discharged from the ED are low. What did this study
      ask? Can a simple quality improvement intervention increase the initiation of
      appropriate OAC in the ED? What did this study find? The rate of OAC initiation
      was increased by 8.5%. Why does this study matter to clinicians? This simple
      intervention is transferrable and therefore can improve patient care.

PMID- 30295592
TI  - Balloon Guided Cement Augmentation of Iliosacral Screws in the Treatment of
      Insufficiency Fractures of the Sacrum - Description of a New Method and
      Preliminary Results.
AB  - PURPOSE OF THE STUDY Fragility fractures of the pelvic ring in the elderly
      population are a serious problem in orthopaedics. The treatment options range
      from conservative treatment to diverse operative options. We present a balloon
      guided new technique of implanting cement augmented screws aiming at improved
      implant anchorage and reduced cement leakage. MATERIAL AND METHODS We describe a
      new technique of balloon- guided cement augmented iliosacral screws. After the
      balloon has been insufflated and contrast medium has been instillated for leakage
      detection, iliosacral screws can safely be placed with a relevant cement depot.
      RESULTS All patients (n = 8) treated in this way were allowed to weight bear on
      both legs and mobilisation was tolerated the next day after surgery. In the post
      operative controls including X-ray and CT scan we noticed no cement leakage. Pain
      level as measured by the visual analog scale was significantly reduced to pre-
      surgery (mean 7.6 pre-operatively, mean 2.5 postoperatively). In addition pain
      medication could be reduced gradually soon after surgery. CONCLUSIONS The
      described procedure to address fragility fractures of the pelvic ring is a safe
      and easy to handle method. There are three advantages: First the osteoporotic S1
      vertebral body can by stabilised by the amount of cement; second the cement
      leakage can be prevented by the balloon-compaction of the cancellous bone and the
      possibility to control the created cavity with contrast medium; third the bone -
      screw interface is much stronger compared to other procedures and is
      biomechanically superior against vertical shear stress. In contrast to
      sacroplasty, the cement application is guided by the previous use of a balloon.
      Key words:pelvic ring, fragility fracture, osteoporosis, elderly.

PMID- 30295593
TI  - [Growth Guidance System in Treatment of Early Onset Scoliosis].
AB  - PURPOSE OF THE STUDY The Growth Guidance System (GGS) represent a relatively new
      alternative to the traditional growing systems used for the treatment of early
      onset scoliosis. Ranking among the main aims of this surgical treatment is a
      three-dimensional correction of the deformity, maintenance of spinal growth and
      postponement of the necessity of final treatment by spondylodesis. MATERIAL AND
      METHODS Our study retrospectively evaluates the results of surgical correction in
      a group of 35 patients treated by GGS technique. The group consisted of patients
      with idiopathic, neuromuscular and syndromic spine deformity with the average age
      of 8 years and 2 months at the time of the surgery. The time of the follow-up is
      3 years and 5 months on average. We evaluated the correction of the curve itself,
      the growth of the spine measured in the thoracic and lumbar part separately, and
      the growth of the trunk as a whole in the mentioned range on X-ray pictures.
      RESULTS The average correction of the scoliotic curve was 67%, from 75
      preoperative degrees to 20 postoperative degrees. After the first operation 11%
      elongation of the trunk (from 321 mm to 356 mm) was reached, the thoracic spine
      was elongated by 10% (from 196 to 217 mm) and the lumbar spine was elongated by
      11% (from 125 to 139 mm). The elongation of the trunk by 16% (from 322 to 375 mm)
      was observed in the cohort of patients with two years postoperative follow-up (21
      patients). The total protraction of the trunk by 21% (from 318 to 386 mm) was
      reached in patients treated by definitive fusion (7 patients). DISCUSSION There
      is a very low number of studies analysing the long-term clinical results with the
      use of GGS. The first pilot results indicate that it is a technique allowing to
      achieve at least comparable results in correction of frontal plane compared with
      the distraction type of instrumentations. A negative aspect of this method is the
      abrasion of metal followed by metallosis. The new types of fixation screws enable
      more effective sliding of rods, maintenance of continuity of body grow by the
      shifting of rods as well as lower abrasion of the instrumentation. CONCLUSIONS
      The main advantage of GGS is the limited continuous growth of the spine, partial
      three-dimensional correction of the deformity, minimisation of inevitable
      reoperations under general anaesthesia and the possibility to quit a brace. Key
      words: growth guided system, early onset scoliosis, distraction, spinal growth,
      spondylodesis.

PMID- 30295594
TI  - [Anatomical All-Inside Anterior Cruciate Ligament Reconstruction Using Quadrupled
      Semitendinosus Tendon Graft with Posteromedial Harvest - Clinical Results of
      Prospective Study at a Minimum 12-Months Follow-up].
AB  - PURPOSE OF THE STUDY This original paper aims to present the conclusions of the
      prospective study evaluating the clinical results of anatomical all-inside ACL
      reconstruction using quadrupled semitendinosustendon graft with posteromedial
      harvest using suspensory fixation by Tightrope implants at the follow-up of at
      least 12 months. MATERIAL AND METHODS The prospective study included a total of
      119 patients (74 men/39 women) with the mean age of 28.3 (18-52) years, in whom
      demographic data was collected and a clinical examination was performed. The
      patients satisfying the "inclusion" and "exclusion" criteria were enrolled in the
      study and subsequently underwent the same, aforementioned surgical procedure
      performed by a single surgeon. Preoperatively and at a minimum 12-month follow-up
      the following subjective criteria were evaluated using the Lysholm and IKDC
      subjective scores and the Visual Analogue Scale (VAS) (0-10). The objective
      parameters comprised the side-to-side difference in anterior knee laxity assessed
      by Genourob arthrometer with an applied pressure of 134 and 250 N, anterior
      drawer test, and the pivot shift test. The occurrence of graft failure,
      complications and return to pre-injury sport levels were monitored. The obtained
      data was statistically evaluated at the statistical significance level of 0.05.
      RESULTS A total of 89 patients were assessed at the follow-up of at least 12
      months after the surgery. The median Lysholm score increased over time from 58.7
      preoperatively to 94.2 postoperatively (p < 0.05) and the IKDC subjective score
      went up from 46.3 to 91.4 (p < 0.05). The median postoperative VAS kept
      decreasing from 7.3 (Day 2), 5.1 (Day 14), 3.1 (Week 6), 1.2 (Month 6) to 0.3 at
      12 months after the surgical procedure. Preoperatively, the results were
      significantly positive (i.e. C, D) in 52.8% (C) and 21.4% (D), whereas
      postoperatively the results of the PST were significantly positive only in 4%.
      Therefore, the surgical procedure was conducive to a statistically significant
      decrease in rotational knee laxity over time (p < 0.05). The median side-to-side
      difference in anterior laxity of the operated knee objectively assessed by GNRB
      arthrometer with the applied pressure of 134 N was 4.2 mm (3.1-6.8) as against
      the postoperative 1.2 mm (0.4-2.1) and with the applied pressure of 250 N it was
      6.2 mm (4.6-8.7) prior to the surgical procedure versus 2.4 mm (1.6-3.5)
      postoperatively. That concerned a statistically significant decrease of
      postoperative side-to-side difference in anterior laxity of the operated knee at
      both the measured pressures (p < 0.05). The graft failed in 3 patients only
      (3.4%), no major complications associated with the surgical procedure were
      observed and 62 of the evaluated patients (69.6%) were able to return to the pre
      injury level of sport within one year after the surgery. DISCUSSION When
      comparing the results obtained by our study with the conclusions of clinical
      studies carried out by other authors and evaluating similar clinical parameters
      with the identical surgical technique applied, it is obvious that in our group of
      patients we achieved similar clinical results as the other authors from abroad.
      CONCLUSIONS The results of our study showed that the all-inside ACL anatomical
      reconstruction using quadrupled semitendinosus tendon graft with posteromedial
      harvest with suspensory fixation by Tightrope implants at one year after the
      surgery bring very good subjective as well as objective clinical results and
      minimum complications. Key words:anterior cruciate ligament tear, anatomical ACL
      reconstruction, all-inside technique, posteromedial harvest, quadrupled
      semitendinosustendon graft, retrograde drilling, suspensory graft fixation.

PMID- 30295595
TI  - Use of Mother-Child Screws in the Treatment of Coronoid Fractures in Terrible
      Triad Injury of the Elbow.
AB  - PURPOSE OF THE STUDY This study aims to analyze the clinical and radiographic
      outcomes of a consecutive series of 18 patients with terrible triad injury. The
      coronoid fractures of these patients were repaired using Mother-Child screw
      (MCS). MATERIAL AND METHODS Twelve men and six women (mean age: 47.2 years) with
      terrible triad injury of the elbow were followed up for a mean of 17.6 months
      (range: 13-42 months). Surgical treatment consisted of open reduction and
      internal fixation of coronoid fractures with MCS, radial head fracture with MCS
      (Mason type II, n = 10), or mini-plate (Mason type III, n = 3). Furthermore, all
      underwent lateral collateral ligament repair (n = 9, 100%), and in cases of
      persistent instability, medial collateral ligament repair was performed (n = 3,
      33%). RESULTS At last follow-up, average arc of ulnohumeral motion was 130
      degrees  (range: 65 degrees  to 150 degrees ), average arc of forearm rotation
      was 148 degrees  (range: 100 degrees -160 degrees ), mean Disabilities of the
      Arm, Shoulder and Hand (DASH) score was 7.1 (range: 0-28.5), and mean Mayo Elbow
      Performance Score (MEPS) was 92 (range: 70-100). According to the Mayo Elbow
      Performance Index (MEPI), 10 patients were excellent in, seven patients were
      good, and one patient was fair. All patients had a stable elbow. No secondary
      coronoid fragment dislocation or implant failures was reported. Fracture healing
      was observed in all patients. CONCLUSIONS This study shows that coronoid fracture
      treatment with MCS may be a new, effective and easy therapeutic option in
      terrible triad injury. Key words:terrible triad of the elbow, coronoid process,
      radial head, functional outcome.

PMID- 30295596
TI  - Arthroscopic Excision of Tendinous Giant Cell Tumors Causing Locking in the Knee
      Joint.
AB  - PURPOSE OF THE STUDY Non-osseous giant cell tumors are locally aggressive tumors
      arising around joints. They are commonly located around synovial joints such as
      wrist and knee and occasionally cause mechanical symptoms. MATERIAL AND METHODS
      This retrospective case series includes 7 patients operated due to intraarticular
      lesion. The mean age of the patients was 28.7 (range 22-37) years. Mean follow-up
      period was 12 months. RESULTS All patients underwent arthroscopic debridement.
      They were followed monthly with clinical examination and magnetic resonance
      imaging (MRI) was obtained at third month for all patients. Patients were
      contacted through phone call and evaluated with the WOMAC score retrospectively.
      No recurrence was detected in any patient. CONCLUSIONS Arthroscopic debridement
      is a safe surgical technique that may replace open surgery in the treatment of
      intraarticular tendinous giant cell tumors. Key words:tendinous giant cell tumor,
      arthroscopy, knee locking.

PMID- 30295597
TI  - [Suprapatellar Nailing of Tibial Fractures - Evaluation of Clinical and
      Radiological Results].
AB  - PURPOSE OF THE STUDY The locked nailing of diaphyseal fractures of the tibia
      currently represents a method of choice for treating the closed diaphyseal
      fractures, some of the tibial metaphyseal fractures and open tibial diaphyseal
      fractures classified as grade I and II according to Gustilo-Anderson (GA)
      classification. The suprapatellar (SP) approach is an alternative technique of
      insertion of the nail in semi-extension of the lower extremity with easier
      reduction, namely of multiple fractures and proximal diaphyseal fractures of the
      tibia in particular. This study aims to evaluate the group of patients in whom
      the suprapatellar approach was used and who were followed up for the period of at
      least 12 months. MATERIAL AND METHODS The prospective study included 55 cases of
      osteosynthesis of diaphyseal fractures of the tibia with the surgery performed in
      the period from January 2013 to June 2015, of which in 53 patients (17 women and
      36 men) with the mean age of 49.6+/- 16.7 years the ETN nail by DePuy Synthes (r)
      was inserted through a suprapatellar approach. In 38 cases (70.1%) an isolated
      trauma was involved, 15 patients (29.9%) were treated for multiple injuries or
      polytrauma. In nine cases (17%) it was an open fracture (2times - GA grade I,
      7times - GA grade II). A multiple fracture or a fracture of the proximal third
      was recorded in 19 cases (34.5%). The functional and radiological results of the
      treatment were assessed prospectively at 12 months after the surgery using the
      Lysholm (LS) score. RESULTS The final functional results were successfully
      assessed in 49 performed osteosyntheses (89.1%). The mean duration of surgery was
      72.7+/- 19.57 min (40-140 min, median 65 min). A total of 48 (98%) fractures
      healed by primary intention. In five cases (10.2%) a delayed healing occurred and
      in one case (2 %) non-union was reported, requiring a revision surgery. In three
      cases (6.1%) complete implant was removed (twice by SP and once by IP approach).
      The mean Lysholm score was 93.4 +/- 8.39 points (59-100 points, median score of
      95 points). An excellent or a good result was observed in 45 patients (91.8%), a
      satisfactory result in three patients (6.2%), and a poor result in one patient
      (2%). A statistically significant correlation (p = 0.006) between the LS score
      values and the age of the patients was confirmed. In patients up to 60 years of
      age the LS score was 96.2 +/- 4.51 points (89-100, median 96), at the age of more
      than 60 years it was 86.9 +/- 11.46 (59-100, median 89). CONCLUSIONS The
      suprapatellar approach in treating the tibial diaphyseal fractures represents a
      safe alternative nail insertion technique. If an appropriate surgical technique
      is applied, the risks inherent in this approach are negligible. The approach
      allows for an easy reduction of challenging fractures of the proximal third
      diaphyseal fracture of the tibia and multiple fractures of the tibia and
      facilitates an easy check of the axial position of the extremity. The functional
      results of the knee joint are comparable to those achieved with the infrapatellar
      nailing technique. The final LS score correlates with the age of the patients.
      Key words:tibial fractures, suprapatellar approach, intramedullary nailing, knee
      pain.

PMID- 30295598
TI  - [Proximal Row Carpectomy - Five-Year Results].
AB  - PURPOSE OF THE STUDY This study aims to evaluate the results of patients treated
      by proximal row carpectomy at a follow-up of at least 5 years after the surgery.
      MATERIAL AND METHODS A total of 25 patients were treated by proximal row
      carpectomy for degenerative changes of the wrist as a consequence of the previous
      trauma or avascular necrosis of the lunate bone, of whom 21 patients underwent a
      follow-up examination at least 5 years postoperatively. Proximal row carpectomy
      was indicated in 15 patients for SLAC wrist, in 4 patients for avascular necrosis
      of the lunate bone, in 1 patient for SNAC wrist, and in 1 patient for inveterate
      dislocation of the wrist. The follow-up clinical and radiological examinations
      were performed at least 5 years after the surgery. The range of wrist motion,
      grip strength, presence of pain at rest or pain under loads, total clinical score
      according to the Green and O'Brien scoring system, patient satisfaction with the
      outcome of surgery were assessed. By fluoroscopy the range of wrist motion,
      degenerative changes of the radiocapitate joint, and translation of the capitate
      bone with respect to the distal radius were evaluated. RESULTS Postoperative
      improvements in the range of motion and grip strength were confirmed. Also, the
      pain relief at rest and under loads was achieved. Five years after the surgery,
      most of the patients (85.6%) reported an overall improvement. The total clinical
      score according to the Green and O'Brien scoring system improved from 35.8
      preoperatively to 63.1 postoperatively. DISCUSSION The advantage of this
      procedure is a low percentage of complications, relative technical simplicity,
      maintenance of functional motion of the wrist, satisfactory grip strength, and
      pain relief. There are no complications related to the implant, no risk of a non
      union. CONCLUSIONS As shown by our results obtained 5 years after the surgery as
      well as the published data, in the indicated cases the proximal row carpectomy is
      an appropriate surgical technique to treat the degenerative changes of the wrist.
      In most of the patients, favourable functional results and pain relief can be
      expected. Key words:proximal row carpectomy, SLAC wrist, SNAC wrist, avascular
      necrosis of the lunate bone, dislocation of the wrist.

PMID- 30295599
TI  - [Interposition and Suspension Arthroplasty of Carpometacarpal Joint of the Thumb
      Using the TIE-IN Implant].
AB  - PURPOSE OF THE STUDY The aim of the study was to present the surgical technique
      combining the interposition and suspension arthroplasty using the TIE-IN implant
      as a treatment option for advanced symptomatic to final stage rhizarthrosis.
      MATERIAL AND METHODS Since 2015 we have performed the interposition arthroplasty
      combined with suspension arthroplasty using the TIE-IN implant in 12 patients,
      mostly indicated for stage IV rhizarthrosis. In two cases stage III rhizarthrosis
      with concomitant trapezium destruction was present. In two other cases the
      patients suffered from secondary osteoarthrosis associated with rheumatoid
      arthritis. Pain under loads was present in all the patients, of whom in 10
      patients also the pain at rest occurred. Preoperatively, a total of 10 patients
      showed subluxation of the first carpometacarpal joint of 50% of the articular
      surface width. The ratio between the dominant and non-dominant extremity was 1:1.
      As a part of the evaluation, correlation was established between the preoperative
      findings and the postoperative results at 3 months follow-up. The examination
      included the assessment of pain intensity by VAS scale, the range of motion
      measurement - by Kapandji thumb opposition test, handgrip strength test and
      functional evaluation using the scoring systems - DASH score, modified DASH score
      for thumb, and modified Wrightington score. RESULTS No intraoperative or
      postoperative complications such as infection, complex regional pain syndrome,
      implant failure or failed surgical procedure were reported in the given group of
      patients. The pain at rest ceased in all 12 patients. The VAS pain intensity
      score improved from the preoperative average of 5.8 to 0.8 postoperatively. The
      range of motion in all the patients with stage IV rhizarthrosis substantially
      improved. The average Kapandji thumb opposition score increased from 6.9
      preoperatively to 9.5 postoperatively. DISCUSSION There are multiple surgical
      treatment options for advanced rhizarthrosis. Apart from the combination of
      interposition and suspension arthroplasty referred to above, it is
      trapeziometacarpal (TMC) arthrodesis on the one hand and carpometacarpal joint
      total arthroplasty on the other hand. The arthrodesis continues to be a fairly
      frequently used procedure, despite the final limitation of thumb movement. It is
      because of this loss of fine motor function why it is not the preferred technique
      for treating advanced rhizarthrosis at our department. On the very contrary, the
      total replacement of the TMC joint is at our department as well as at many other
      departments the treatment of choice for advanced symptomatic rhizarthrosis since
      in conservative resection of the articular surfaces the biomechanics of the
      carpometacarpal joint of the thumb is preserved. As an outcome, this technique
      combines the advantages of other surgical methods by ensuring full painless range
      of motion and strength of the joint as opposed to other techniques, which mostly
      result either in a limited movement, or in a loss of grip strength. There is a
      whole range of resection arthroplasty techniques available. From simple
      trapeziectomy, which leads to the radial column collapse and ultimately to a
      major functional deficit, up to various interposition or suspension arthroplasty
      techniques with the resulting range of motion, stability and thus grip strength
      depending on the technique applied. CONCLUSIONS By applying the combination of
      the interposition and suspension arthroplasty of the carpometacarpal joint of the
      thumb using the TIE-IN implant we preserve the length of the thumb, its
      stability, and thus achieve the recovery of adequate thumb range of motion and
      grip strength. Our conclusions are in correlation with the results obtained at
      reference centres. Key words:rhizarthrosis, trapeziometacarpal prosthesis,
      arthroplasty, trapezium implant.

PMID- 30295600
TI  - [Short-Term Results of the Carpometacarpal Joint Arthroplasty Using the Ivory(r)
      Prosthesis].
AB  - PURPOSE OF THE STUDY Trapeziometacarpal osteoarthritis affects primarily
      postmenopausal middle-aged and older women. Total joint replacement is one of the
      surgical treatment options for symptomatic advanced degenerative changes of the
      carpometacarpal joint. This study aims to evaluate the short-term functional and
      radiological results of the Ivory (r) prosthesis with the minimum followup period
      of three years after the surgery. MATERIAL AND METHODS Presented are the results
      of 48 total trapeziometacarpal joint replacements in the group of 40 patients
      composed of 36 women and 4 men. The age of patients ranges from 41 to 75 years
      (median 56 years), with the ratio between the dominant and non-dominant upper
      extremity 23:25. The follow-up period ranged from 36 to 63 months (median 52
      months). The surgery was indicated in patients with symptomatic
      trapeziometacarpal arthrosis of stage II, III and early stage IV according to
      Eaton-Glickel once the conservative therapy had failed. In all the patients, the
      evaluation of the function and pain of the operated joint by DASH score, the
      range of motion -thumb opposition by Kapandji score were carried out at regular
      intervals pre- and postoperatively, the radiological evaluation of the stage of
      degenerative joint condition was done preoperatively, whereas the position of the
      implant and the lengthening of the first column of the finger were assessed
      postoperatively. RESULTS Subjectively, the patients were satisfied with the
      result of the surgery. After the joint replacement, in 65% of cases the patients
      reported full satisfaction with no difficulties present, in 31% of cases the
      patients suffered from pain during loading, in 4% of cases the patients reported
      also occasional pain at rest. Postoperatively, the total DASH score values
      decreased from the mean preoperative value of 52.79 to 10.4 points at a three
      year follow-up. The average value of pain dropped from 3.46 to 1.44 points 3
      years after the surgery. The average range of motion - thumb opposition by
      Kapandji score increased from 8.57/10 to 9.85/10 one year after the surgery. The
      difference between the values of average increase in length of the first column
      of the finger was 0.14 mm in favour of the sub-group of symptomatic cases. In the
      evaluated group, the need for revision was determined in 4 implants. In 1case for
      aseptic loosening of the cup and three times for dislocation. After 36 months, 47
      of 48 implants were in situ, the overall three-year survival was achieved in
      97.9%. The most frequent postoperative complication was the occurrence of De
      Quervain s tenosynovitis (10%). DISCUSSION Currently, most of the newer types of
      modular uncemented hydroxyapatite-coated total "ball and socket" joint
      replacements present acceptable medium-term, and in some cases even long-term,
      results regarding the survival. The most pressing issue continues to be the
      survival of implants, particularly the failure of the trapezial component and the
      associated risk of revision surgery. Good postoperative results can be achieved
      by accurate indication, carefully applied cup implant and good postoperative
      cooperation of patients. The complementary study did not confirm that the
      lengthening of the thumb causes the postoperative development of De Quervain s
      tenosynovitis. CONCLUSIONS The uncemented first carpometacarpal joint total
      replacement using the Ivory (r) prosthesis brings about very good shortterm
      functional and radiological results, with no occurrence of early aseptic
      loosening of the implant. Key words:rhizarthrosis, arthroplasty, carpometacarpal
      joint prosthesis, uncemented.

PMID- 30295601
TI  - [Changes in Cognitive Functions after Total Hip Arthroplasty].
AB  - PURPOSE OF THE STUDY The postoperative delirium is a frequent, oftentimes
      underestimated complication of total hip arthroplasty. Its occurrence is reported
      to be between 10% and 50%. The postoperative delirium increases mortality, the
      length of hospital stay and leads to worse functional results. Even though there
      is evidence of efficiency of preventive measures and effectiveness of treatment
      interventions, inadequate attention has been paid so far to this serious
      complication related to inpatient hospital care. This paper aimed to determine
      the incidence of cognitive function impairment in relation to the total hip
      replacement, to determine the influence of the defined parameters on changes in
      cognitive functions and to draft practice guidelines for the care of patients
      after a total hip replacement in the framework of prevention and early detection
      of changes in cognition of patients after total hip replacement. MATERIAL AND
      METHODS Prospective observational descriptive study, the evaluated parameters
      included: type of anaesthesia, duration of surgical procedure (operation), type
      of analgesia, O2 saturation, haemoglobin levels, changes in the ionogram, body
      temperature, presence of concomitant diseases, polypragmasia, abuse, level of
      self-sufficiency of patients evaluated by ADL. In order to obtain the data, the
      Mini Mental State Examination (MMSE), the Abbreviated Mental Test Score (AMTS),
      Recall and naming test, and the Activities of Daily Living Test (ADL) were used.
      The monitored group of patients included a total of 116 persons, of whom 68 men
      and 48 women. The mean age was 71.16 years; the range from 65 to 86 years; median
      - 72.36 years. RESULTS A statistically significant dependence was revealed
      between the change in cognitive functions and all the monitored parameters,
      except for the haemoglobin levels after 120 hours postoperatively, ion levels
      after 120 hours and sex by the 10-point Mini Mental Test score. A statistically
      significant dependence was revealed between the change in cognitive functions and
      02 saturation, ion levels, elevated body temperature after 120 hours
      postoperatively, age, diabetes, polypragmasia and in correlation with the ADL 120
      hours postoperatively by the MMSE test. A statistically significant dependence
      was revealed between the change in cognitive functions and all the monitored
      parameters, except for anaesthesia and analgesia, haemoglobin levels after 24 and
      120 hours, ion levels after 120 hours, renal insufficiency and in correlation
      with the ADL after 24 hours by the "Recall and naming" test. DISCUSSION The
      correlation between delirium and long-term cognition impairment was described by
      several studies. Both the recent literature and our study clearly indicate a
      correlation between the postoperative cognitive impairment on the one hand and
      polypragmasia, age, presence of concomitant diseases on the other hand. In some
      parameters such as the sex of the patient its influence was not clearly
      established by the relevant literature or our study. The perioperative factors
      influencing the onset of delirium referred to in literature are anaesthesia and
      its duration. Our study reveals the correlation between the anaesthesia and the
      onset of cognitive impairment when evaluated by the Abbreviated Mental Test
      Score. As regards the monitored postoperative parameters, the influence of
      postoperative hyposaturation, decreased haemoglobin level, changes in ionogram,
      elevated body temperature, lower self-sufficiency of the patient was established.
      Also our study shows the correlation between the change in the aforementioned
      parameters and the cognitive impairment, even though not quite clearly in all the
      parameters. The most sensitive evaluation tool turned out to be the Abbreviated
      Mental Test Score. CONCLUSIONS Our study clearly showed that a highly sensitive
      test to detect the current changes in cognition in a short-term horizon is the
      Abbreviated Mental Test Score. Based on the statistically significant factors
      determining the onset of the change in cognition that we had revealed, we
      elaborated a clearly arranged scheme of identified risk factors and interventions
      for the prevention and early identification of the onset of changes in cognitive
      functions and potential delirium. Key words:total hip arthroplasty, cognitive
      impairment, delirium.

PMID- 30295602
TI  - [Penetrating Injuries of the Heart and Great Vessels - Fifteen Years of
      Experience of the Cardiac Surgery Service as a Part of the Major Trauma Centre].
AB  - PURPOSE OF THE STUDY Outcome analysis of penetrating cardiac and great vessels
      injury within the 15-year existence of the cardiac surgery service as a part of
      the major trauma centre of the University Hospital Olomouc MATERIAL AND METHODS
      Retrospective analysis of a group of a total of 16 patients who underwent a
      surgery for penetrating cardiac and great vessels injury since II/2002 to
      XI/2016. The dominant causes of penetrating trauma were stab injuries (15
      patients, 94%), in one patient only (6%) it was a gunshot injury. The mean age of
      the patients included in the group was 42.9 +/- 16.1 years, with men
      significantly prevailing (13 patients, 81%). A total of 7 injured persons (44%)
      were haemodynamically stable when admitted, 9 injured persons (56%) were unstable
      or in critical condition. The average transfer distance was 48.8 +/- 34.5 km; the
      injured were admitted on average 115.9 +/- 154.8 minutes after being injured.
      Preoperatively, all the injured suffered from pericardial effusion (>5 mm)
      confirmed by TTE (81%) or CTA (19%). In 4 patients (25%) pericardial drainage for
      cardiac tamponade was performed before surgery. RESULTS All the penetrating
      cardiac and great vessels injuries were repaired by cardiac surgeon, in one case
      only (6%) the extracorporeal circulation support was used. The injury of coronary
      arteries was in one case managed by CABG and in the other case by ligation of the
      peripheral part of the coronary artery. In 4 patients (25%) also a penetrating
      injury of other organs was simultaneously managed. The mean ICU stay reached 85.8
      +/- 91.9 hours, on average 5.6 +/- 9.3 units of red blood cells were administered
      during the in-hospital stay which lasted on average 7.1 +/- 2.4 days. In the
      group a nonsignificant increase of left ventricular ejection fraction (44.1 +/-
      4.7 vs. 49.3 +/- 3.2, p = 0.882) was reported at discharge of the injured
      patients. One patient died on the 78 th day of hypoxic brain damage (6% three
      month mortality). The long-term survival analysis showed 94% one-year and 88%
      five-year cumulative survival in the group. DISCUSSION The incidence of the
      penetrating cardiac and great vessels injury is directly dependent on the crime
      level in the respective countries and regions. A cardiac arrest, severe
      hemodynamic instability, unconsciousness, serious concomitant injury, gunshot
      injury, multiple or atrial injury represent independent predictors of death in
      these injuries. The total three-month mortality in penetrating cardiac and great
      vessels injury ranges from 18 to 42%, the presence of vital signs at the time of
      hospital admission is associated with 78-92% probability of survival. The
      surviving patients show excellent long-term results with the exception of those
      who suffered a severe damage to valve apparatus or with significantly depressed
      left ventricular function. CONCLUSIONS Our experience proves a high survival rate
      of patients with penetrating cardiac and great vessels injury. The centralisation
      of the care into the major trauma centre with a cardiac surgery background, a
      unified treatment algorithm, and a vital interdisciplinary cooperation are the
      key goal of successful management of these injuries. Key words:penetrating
      injury, cardiac injury, great vessel injury, outcome. Prace byla podporena
      programem institucionalni podpor.

PMID- 30295603
TI  - [Anterior Penetrating Sacral Injury in a 14-Year-Old Girl - a Case Report].
AB  - Anterior penetrating sacral injuries in children are extremely rare. These
      injuries are coupled with both a high energy mechanism (combat injury, motor
      vehicle accidents) and with foreign body impalement. The treatment is individual,
      laparotomy with penetrating wound exploration is indicated, osteosynthesis is
      performed in case of grossly displaced fractures, in an unstable injury to the
      posterior pelvic ring, and urgently in case of a neurological injury. The case
      report describes a 14-year-old girl with a left-sided anterior penetrating sacral
      injury at the level of S2/S3, who was injured during a bicycle accident
      (impalement on handlebars). The emergent laparotomy was performed first to treat
      the lesion of the sigmoid mesocolon. After 16 days the patient underwent the
      second operation, when open fragment reposition and sacral bone suture were
      performed. Both the sacral fracture and soft tissues were healed in 6 weeks. The
      patient was fully weight bearing and without pain. Key words:pediatric sacral
      fracture, penetration, treatment.

PMID- 30295604
TI  - BRCT domains of the DNA damage checkpoint proteins TOPBP1/Rad4 display distinct
      specificities for phosphopeptide ligands.
AB  - TOPBP1 and its fission yeast homologueRad4, are critical players in a range of
      DNA replication, repair and damage signalling processes. They are composed of
      multiple BRCT domains, some of which bind phosphorylated motifs in other
      proteins. They thus act as multi-point adaptors bringing proteins together into
      functional combinations, dependent on post-translational modifications downstream
      of cell cycle and DNA damage signals. We have now structurally and/or
      biochemically characterised a sufficient number of high-affinity complexes for
      the conserved N-terminal region of TOPBP1 and Rad4 with diverse phospho-ligands,
      including human RAD9 and Treslin, and Schizosaccharomyces pombe Crb2 and Sld3, to
      define the determinants of BRCT domain specificity. We use this to identify and
      characterise previously unknown phosphorylation-dependent TOPBP1/Rad4-binding
      motifs in human RHNO1 and the fission yeast homologue of MDC1, Mdb1. These
      results provide important insights into how multiple BRCT domains within
      TOPBP1/Rad4 achieve selective and combinatorial binding of their multiple partner
      proteins.

PMID- 30295605
TI  - The allosteric activation of cGAS underpins its dynamic signaling landscape.
AB  - Cyclic G/AMP synthase (cGAS) initiates type-1 interferon responses against
      cytosolic double-stranded (ds)DNA, which range from antiviral gene expression to
      apoptosis. The mechanism by which cGAS shapes this diverse signaling landscape
      remains poorly defined. We find that substrate-binding and dsDNA length-dependent
      binding are coupled to the intrinsic dimerization equilibrium of cGAS, with its N
      terminal domain potentiating dimerization. Notably, increasing the dimeric
      fraction by raising cGAS and substrate concentrations diminishes duplex length
      dependent activation, but does not negate the requirement for dsDNA. These
      results demonstrate that reaction context dictates the duplex length dependence,
      reconciling competing claims on the role of dsDNA length in cGAS activation.
      Overall, our study reveals how ligand-mediated allostery positions cGAS in
      standby, ready to tune its signaling pathway in a switch-like fashion.

PMID- 30295608
TI  - A Wearable Multifunctional Pulse Monitor using Thermosensation-based Flexible
      Sensors.
AB  - OBJECTIVE: This study proposes a novel wearable pulse monitoring system, which
      can realize the synchronous measurements of pulse wave, skin temperature and
      pulse wave velocity (PWV). METHODS: A flexible sensor based on thermosensation is
      used to detect pressure and temperature stimuli simultaneously. Two sensors are
      integrated to detect pulse transit along two specific points of artery, e.g. Cun
      and Chi at a wrist, the data of which are subsequently used to figure out the PWV
      by using a tailor-designed algorithm conducted in a microprocessor. Calibration
      experiments and application cases are conducted to validate the effectiveness of
      the monitor. RESULTS: The developed monitor detects the physiological signals of
      pulse wave, PWV and skin temperature simultaneously. In addition, the monitor can
      measure the pulse changes before and after exercises, and tract skin temperature
      variations when warming and cooling. Moreover, the monitor can be also used to
      detect the local PWV at wrist. CONCLUSION: The synchronous measurements of pulse
      wave, skin temperature and PWV using a wearable monitor are feasible.
      SIGNIFICANCE: The monitor is small, simple-structured, with multifunction, and
      thus provides a promising auxiliary approach for traditional Chinese medicine
      (TCM) pulse diagnosis.

PMID- 30295609
TI  - A Fully Automated 3D In-vivo Delineation and Shape Parameterization of the Human
      Lamina Cribrosa in Optical Coherence Tomography.
AB  - OBJECTIVE: A fully automated method for delineation of the lamina cribrosa in
      optical coherence tomography (OCT) is proposed. It assesses the 3D shape of the
      lamina cribrosa in-vivo, based on a series of OCT B-scans. METHODS: The algorithm
      has several image processing steps and it is based on active contour detection
      performed along three orthogonal directions of the B-scan data cuboid. Further,
      the delineated 3D lamina cribrosa shape is parameterized with a fourth-order
      polynomial of two variables, P[x, y] using the least-squares method. Data sets
      from a total of 255 subjects from three groups were analyzed: 92 primary open
      angle glaucoma patients, 77 glaucoma suspects, and 86 controls. RESULTS:
      Statistically significant differences () were found in the coefficients of
      monomials , with both i and j even, between patients and controls and between
      suspects and controls. CONCLUSIONS: From the data obtained, it can be concluded
      that the mean shape parameterization of the lamina cribrosa of glaucoma suspects
      has similar appearance to that of glaucoma patients but it is markedly different
      from that of healthy controls. SIGNIFICANCE: The proposed algorithm enables
      automatically estimating, for the first time, the lamina cribrosa in 3D, further
      providing clinicians with a time efficient discrimination tool supporting
      glaucoma diagnosis.

PMID- 30295610
TI  - Source-Informed Segmentation: A Data-Driven Approach for the Temporal
      Segmentation of EEG.
AB  - GOAL: Understanding the dynamics of brain function through non-invasive
      neuroimaging techniques requires the development of computational techniques that
      can deal with the non-stationary properties of recorded activities. As a solution
      to this problem, a new data-driven segmentation method for recordings obtained
      through electroencephalography (EEG) is presented. METHODS: The proposed method
      utilizes singular value decomposition (SVD) to identify the time intervals in the
      EEG recordings during which, the spatial distribution of clusters of active
      cortical neurons remains quasi-stationary. Theoretical analysis shows that the
      spatial locality features of these clusters can be, asymptotically, captured by
      the most significant left singular subspace of the EEG data. A reference/sliding
      window approach is employed to dynamically extract this feature subspace, and the
      running error is monitored for significant changes using Kolmogorov-Smirnov (K-S)
      test. RESULTS: Simulation results, for a wide range of possible scenarios
      regarding the spatial distribution of active cortical neurons, show that the
      algorithm is successful in accurately detecting the segmental structure of the
      simulated EEG data. The algorithm is also applied to experimental EEG recordings
      of a modified visual oddball task. Results identify a unique sequence of dynamic
      patterns in the event-related potential (ERP) response for each of the three
      involved stimuli. CONCLUSION: The proposed method, without using source
      localization methods or scalp topographical maps, is able to identify intervals
      of quasi-stationary in the EEG recordings. SIGNIFICANCE: The proposed
      segmentation technique can offer new insights on the dynamics of functional
      organization of the brain in action.

PMID- 30295606
TI  - Motor thalamus supports striatum-driven reinforcement.
AB  - Reinforcement has long been thought to require striatal synaptic plasticity.
      Indeed, direct striatal manipulations such as self-stimulation of direct-pathway
      projection neurons (dMSNs) are sufficient to induce reinforcement within minutes.
      However, it's unclear what role, if any, is played by downstream circuitry. Here,
      we used dMSN self-stimulation in mice as a model for striatum-driven
      reinforcement and mapped the underlying circuitry across multiple basal ganglia
      nuclei and output targets. We found that mimicking the effects of dMSN activation
      on downstream circuitry, through optogenetic suppression of basal ganglia output
      nucleus substantia nigra reticulata (SNr) or activation of SNr targets in the
      brainstem or thalamus, was also sufficient to drive rapid reinforcement.
      Remarkably, silencing motor thalamus-but not other selected targets of SNr-was
      the only manipulation that reduced dMSN-driven reinforcement. Together, these
      results point to an unexpected role for basal ganglia output to motor thalamus in
      striatum-driven reinforcement.

PMID- 30295607
TI  - Dopamine neuron glutamate cotransmission evokes a delayed excitation in lateral
      dorsal striatal cholinergic interneurons.
AB  - : Dopamine neurons have different synaptic actions in the ventral and dorsal
      striatum (dStr), but whether this heterogeneity extends to dStr subregions has
      not been addressed. We have found that optogenetic activation of dStr dopamine
      neuron terminals in mouse brain slices pauses the firing of cholinergic
      interneurons in both the medial and lateral subregions, while in the lateral
      subregion the pause is shorter due to a subsequent excitation. This excitation is
      mediated mainly by metabotropic glutamate receptor 1 (mGluR1) and partially by
      dopamine D1-like receptors coupled to transient receptor potential channel 3 and
      7. DA neurons do not signal to spiny projection neurons in the medial dStr, while
      they elicit ionotropic glutamate responses in the lateral dStr. The DA neurons
      mediating these excitatory signals are in the substantia nigra (SN). Thus, SN
      dopamine neurons engage different receptors in different postsynaptic neurons in
      different dStr subregions to convey strikingly different signals. Editorial note:
      This article has been through an editorial process in which the authors decide
      how to respond to the issues raised during peer review. The Reviewing Editor's
      assessment is that all the issues have been addressed (see decision letter).

PMID- 30295611
TI  - Rank Minimization for Snapshot Compressive Imaging.
AB  - Snapshot compressive imaging (SCI) refers to compressive imaging systems where
      multiple frames are mapped into a single measurement, with video compressive
      imaging and hyperspectral compressive imaging as two representative applications.
      Though exciting results of high-speed videos and hyperspectral images have been
      demonstrated, the poor reconstruction quality precludes SCI from wide
      applications.This paper aims to boost the reconstruction quality of SCI via
      exploiting the high-dimensional structure in the desired signal. We build a joint
      model to integrate the nonlocal self-similarity of video/hyperspectral frames and
      the rank minimization approach with the SCI sensing process. Following this, an
      alternating minimization algorithm is developed to solve this non-convex problem.
      We further investigate the special structure of the sampling process in SCI to
      tackle the computational workload and memory issues in SCI reconstruction. Both
      simulation and real data (captured by four different SCI cameras) results
      demonstrate that our proposed algorithm leads to significant improvements
      compared with current state-of-the-art algorithms. We hope our results will
      encourage the researchers and engineers to pursue further in compressive imaging
      for real applications.

PMID- 30295612
TI  - Denoising Prior Driven Deep Neural Network for Image Restoration.
AB  - Deep neural networks (DNNs) have shown very promising results for various image
      restoration (IR) tasks. However, the design of network architectures remains a
      major challenging for achieving further improvements. While most existing DNN
      based methods solve the IR problems by directly mapping low quality images to
      desirable high-quality images, the observation models characterizing the image
      degradation processes have been largely ignored. In this paper, we first propose
      a denoising-based IR algorithm, whose iterative steps can be computed
      efficiently. Then, the iterative process is unfolded into a deep neural network,
      which is composed of multiple denoisers modules interleaved with back-projection
      (BP) modules that ensure the observation consistencies. A convolutional neural
      network (CNN) based denoiser that can exploit the multi-scale redundancies of
      natural images is proposed. As such, the proposed network not only exploits the
      powerful denoising ability of DNNs, but also leverages the prior of the
      observation model. Through end-to-end training, both the denoisers and the BP
      modules can be jointly optimized. Experimental results on several IR tasks, e.g.,
      image denoisig, super-resolution and deblurring show that the proposed method can
      lead to very competitive and often state-of-the-art results on several IR tasks,
      including image denoising, deblurring and super-resolution.

PMID- 30295613
TI  - Visual Permutation Learning.
AB  - We present a principled approach to uncover the structure of visual data by
      solving a deep learning task coined visual permutation learning. The goal of this
      task is to find the permutation that recovers the structure of data from shuffled
      versions of it. In the case of natural images, this task boils down to recovering
      the original image from patches shuffled by an unknown permutation matrix.
      Permutation matrices are discrete, thereby posing difficulties for gradient-based
      optimization methods. To this end, we resort to a continuous approximation using
      doubly-stochastic matrices and formulate a novel bi-level optimization problem on
      such matrices that learns to recover the permutation. Unfortunately, such a
      scheme leads to expensive gradient computations. We circumvent this issue by
      further proposing a computationally cheap scheme for generating doubly stochastic
      matrices based on Sinkhorn iterations. To implement our approach we propose
      DeepPermNet, an end-to-end CNN model for this task. The utility of DeepPermNet is
      demonstrated on three challenging computer vision problems, namely, relative
      attributes learning, supervised learning-to-rank, and self-supervised
      representation learning. Our results show state-of-the-art performance on
      relative attributes learning, supervised learning-to-rank, and competitive
      results in the classification and segmentation tasks of the PASCAL VOC dataset
      for self-supervised learning.

PMID- 30295614
TI  - Hyperspectral recovery from RGB images using Gaussian Processes.
AB  - We propose to recover spectral details from RGB images of known spectral
      quantization by modeling natural spectra under Gaussian Processes and combining
      them with the RGB images. Our technique exploits Process Kernels to model the
      relative smoothness of reflectance spectra, and encourages non-negativity in the
      resulting signals for better estimation of the reflectance values. The Gaussian
      Processes are inferred in sets using clusters of spatio-spectrally correlated
      hyperspectral training patches. Each set is transformed to match the spectral
      quantization of the test RGB image. We extract overlapping patches from the RGB
      image and match them to the hyperspectral training patches by spectrally
      transforming the latter. The RGB patches are encoded over the transformed
      Gaussian Processes related to those hyperspectral patches and the resulting image
      is constructed by combining the codes with the original Processes. Our approach
      infers the desired Gaussian Processes under a fully Bayesian model inspired by
      Beta-Bernoulli Process, for which we also present the inference procedure. A
      thorough evaluation using three hyperspectral datasets demonstrates the effective
      extraction of spectral details from RGB images by the proposed technique.

PMID- 30295615
TI  - First-Person Activity Forecasting from Video with Online Inverse Reinforcement
      Learning.
AB  - We address the problem of incrementally modeling and forecasting long-term goals
      of a first-person camera wearer: what the user will do, where they will go, and
      what goal they seek. In contrast to prior work in trajectory forecasting, our
      algorithm, DARKO, goes further to reason about semantic states (will I pick up an
      object?), and future goal states that are far in terms of both space and time.
      DARKO learns and forecasts from first-person visual observations of the user's
      daily behaviors via an Online Inverse Reinforcement Learning (IRL) approach.
      Classical IRL discovers only the rewards in a batch setting, whereas DARKO
      discovers the transitions, rewards, and goals of a user from streaming data.
      Among other results, we show DARKO forecasts goals better than competing methods
      in both noisy and ideal settings, and our approach is theoretically and
      empirically no-regret.

PMID- 30295616
TI  - Transient Convolutional Imaging.
AB  - While traditional imaging systems directly measure scene properties,
      computational imaging systems add computation to the measurement process,
      allowing such systems to extract non-trivially encoded scene features. This work
      demonstrates that exploiting structure in this process allows to recover
      information that is conventionally considered to be "lost". Relying on temporally
      and spatially convolutional structure, we extract a novel image modality that was
      essentially "invisible" before: a new temporal dimension of light propagation,
      obtained with consumer depth cameras. Using conventional Time-of-Flight cameras,
      a few seconds of capture and computation allows us to recover information that
      before could only be acquired in hours of capture time with specialized
      instrumentation at orders of magnitude higher cost. The novel type of image we
      capture allows us to make first steps toward the full inversion of light
      transport. Specifically, we demonstrate that Non-Line-of-Sight imaging and
      imaging in scattering media can be made feasible with the temporally resolved
      light transport acquired using Time-of-Flight depth cameras.

PMID- 30295617
TI  - A Flexible and Modular Receiver Coil Array for Magnetic Resonance Imaging.
AB  - We propose a flexible form-fitting MRI receiver coil array assembled by
      individual coil modules. This design targets MRI applications requiring a
      receiver array conforming to the anatomy of various shapes or sizes. Coil modules
      in our proposed array were arranged with gaps between them. Each coil module had
      a circumferential shielding structure stacked on top of the coil. Together they
      achieve robust decoupling when the array was bent differently. Two types of the
      circumferential shielding structure were investigated by using full-wave
      electromagnetic simulations and imaging experiments. Results showed that our
      flexible coil array had good decoupling between coils whether they were on a flat
      or curved surface with the S21 magnitude ranged between -18.1 dB and -19.9 dB in
      simulations, and with the average of off-diagonal entries of the noise
      correlation matrix less than 0.047 in experimental measurements. Anatomical
      images of human brain, calf, and knee were acquired by our seven-channel
      prototype on a 3T MRI system. The maximal and the average SNR within 50 mm from
      our array surpassed those from the commercial 32-channel head and 4-channel
      flexible coil arrays by 2.63/1.35-fold and 3.89/1.50-fold, respectively.

PMID- 30295618
TI  - Optimal Experiment Design for Magnetic Resonance Fingerprinting: Cramer-Rao Bound
      Meets Spin Dynamics.
AB  - Magnetic resonance (MR) fingerprinting is a new quantitative imaging paradigm,
      which simultaneously acquires multiple MR tissue parameter maps in a single
      experiment. In this paper, we present an estimation-theoretic framework to
      perform experiment design for MR fingerprinting. Specifically, we describe a
      discrete-time dynamic system to model spin dynamics, and derive an estimation
      theoretic bound, i.e., the Cramer-Rao bound (CRB), to characterize the signal-to
      noise ratio (SNR) efficiency of an MR fingerprinting experiment. We then
      formulate an optimal experiment design problem, which determines a sequence of
      acquisition parameters to encode MR tissue parameters with the maximal SNR
      efficiency, while respecting the physical constraints and other constraints from
      the image decoding/reconstruction process. We evaluate the performance of the
      proposed approach with numerical simulations, phantom experiments, and in vivo
      experiments. We demonstrate that the optimized experiments substantially reduce
      data acquisition time and/or improve parameter estimation. For example, the
      optimized experiments achieve about a factor of two improvement in the accuracy
      of T2 maps, while keeping similar or slightly better accuracy of T1 maps.
      Finally, as a remarkable observation, we find that the sequence of optimized
      acquisition parameters appears to be highly structured rather than
      randomly/pseudo-randomly varying as is prescribed in the conventional MR
      fingerprinting experiments.

PMID- 30295619
TI  - SUSHI: Sparsity-based Ultrasound Super-resolution Hemodynamic Imaging.
AB  - Identifying and visualizing vasculature within organs and tumors has major
      implications in managing cardiovascular diseases and cancer. Contrast-enhanced
      ultrasound scans detect slow-flowing blood, facilitating non-invasive perfusion
      measurements. However, their limited spatial resolution prevents the depiction of
      microvascular structures. Recently, super-localization ultrasonography techniques
      have surpassed this limit. However, they require long acquisition times of
      several minutes, preventing the detection of hemodynamic changes. We present a
      fast super-resolution method that exploits sparsity in the underlying vasculature
      and statistical independence within the measured signals. Similar to super
      localization techniques, this approach improves the spatial resolution by up to
      an order of magnitude compared to standard scans. Unlike super-localization
      methods, it requires acquisition times of only tens of milliseconds. We
      demonstrate a temporal resolution of ~25Hz, which may enable functional super
      resolution imaging deep within the tissue, surpassing the temporal resolution
      limitations of current super-resolution methods, e.g. in neural imaging. The sub
      second acquisitions make our approach robust to motion artifacts, simplifying in
      vivo use of super-resolution ultrasound.

PMID- 30295620
TI  - Edit Distance between Merge Trees.
AB  - Topological structures such as the merge tree provide an abstract and succinct
      representation of scalar fields. They facilitate effective visualization and
      interactive exploration of feature-rich data. A merge tree captures the topology
      of sub-level and super-level sets in a scalar field. Estimating the similarity
      between merge trees is an important problem with applications to feature-directed
      visualization of time-varying data. We present an approach based on tree edit
      distance to compare merge trees. The comparison measure satisfies metric
      properties, it can be computed efficiently, and the cost model for the edit
      operations is both intuitive and captures well-known properties of merge trees.
      Experimental results on time-varying scalar fields, 3D cryo electron microscopy
      data, shape data, and various synthetic datasets show the utility of the edit
      distance towards a feature-driven analysis of scalar fields.

PMID- 30295621
TI  - Dictionary-based Fidelity Measure for Virtual Traffic.
AB  - Aiming at objectively measuring the realism of virtual traffic flows and
      evaluating the effectiveness of different traffic simulation techniques, this
      paper introduces a general, dictionary-based learning method to evaluate the
      fidelity of any traffic trajectory data. First, a traffic pattern dictionary that
      characterizes common patterns of real-world traffic behavior is built offline
      from pre-collected ground truth traffic data. The corresponding learning error is
      set as the benchmark of the dictionary-based traffic representation. With the aid
      of the constructed dictionary, the realism of input simulated traffic flow data
      can be evaluated by comparing its dictionary-based reconstruction error with the
      dictionary error benchmark. This evaluation metric can be robustly applied to any
      simulated traffic flow data; in other words, it is independent of how the traffic
      data are generated. We demonstrated the effectiveness and robustness of this
      metric through many experiments on real-world traffic data and various simulated
      traffic data, comparisons with the state-of-the-art entropy-based similarity
      metric for aggregate crowd motions, and perceptual evaluation studies.

PMID- 30295622
TI  - 3D Objects Clouds: Viewing Virtual Objects in Interactive Clouds.
AB  - Given the expanding use of 3D Objects in a variety of fields such as animation,
      gaming, virtual worlds, commerce, augmented reality and 3D printing, we present a
      novel system for object browsing and searching. Specifically, the system packs
      objects into an interactive 3D cloud for browsing and searching on mobile
      devices. It was designed with the aim of increasing search efficiency in a
      variety of active environments, while providing a visually engaging layout, and
      we evaluated this by conducting a comparative user study. We show that our system
      can significantly decrease search times compared to the classic grid-based layout
      that is used extensively, and it has been suggested by subjects that cloud-based
      searching is more interesting and visually-engaging.

PMID- 30295623
TI  - Towards BCI-based Interfaces for Augmented Reality: Feasibility, Design and
      Evaluation.
AB  - Brain-Computer Interfaces (BCIs) enable users to interact with computers without
      any dedicated movement, bringing new hands-free interaction paradigms. In this
      paper we study the combination of BCI and Augmented Reality (AR). We first tested
      the feasibility of using BCI in AR settings based on Optical See-Through Head
      Mounted Displays (OST-HMDs). Experimental results showed that a BCI and an OST
      HMD equipment (EEG headset and Hololens in our case) are well compatible and that
      small movements of the head can be tolerated when using the BCI. Second, we
      introduced a design space for command display strategies based on BCI in AR, when
      exploiting a famous brain pattern called Steady-State Visually Evoked Potential
      (SSVEP). Our design space relies on five dimensions concerning the visual layout
      of the BCI menu; namely: orientation, frame-of-reference, anchorage, size and
      explicitness. We implemented various BCI-based display strategies and tested them
      within the context of mobile robot control in AR. Our findings were finally
      integrated within an operational prototype based on a real mobile robot that is
      controlled in AR using a BCI and a HoloLens headset. Taken together our results
      (4 user studies, 94 participants) and our methodology could pave the way to
      future interaction schemes in AR exploiting 3D User Interfaces based on brain
      activity and BCIs.

PMID- 30295624
TI  - Door and Doorway Etiquette for Virtual Humans.
AB  - We introduce a framework for simulating a variety of nontrivial, socially
      motivated behaviors that underlie the orderly passage of pedestrians through
      doorways, especially the common courtesy of opening and holding doors open for
      others, an important etiquette that has been overlooked in the literature on
      autonomous multi-human animation. Emulating such social activity requires serious
      attention to the interplay of visual perception, navigation in constrained
      doorway environments, manipulation of a variety of door types, and high-level
      decision making based on social considerations. To tackle this complex human
      simulation problem, we take an artificial life approach to modeling autonomous
      pedestrians, proposing a layered architecture comprising mental, behavioral, and
      motor layers. The behavioral layer couples two stages: (1) a decentralized, agent
      based strategy for dynamically determining the well-mannered ordering of
      pedestrians around doorways, and (2) a state-based model that directs and
      coordinates a pedestrian's interactions with the door. The mental layer is a
      Bayesian network decision model that dynamically selects appropriate door holding
      behaviors by considering both internal and external social factors pertinent to
      pedestrians interacting with one another in and around doorways. Our framework
      addresses the various door types in common use and supports a variety of doorway
      etiquette scenarios with efficient, real-time performance.

PMID- 30295625
TI  - Gestural Interaction and Visual Illusion for Lower Limbs' Neuropathic Pain
      Treatment.
AB  - Pain caused by a lesion or a disease affecting the somatosensory nervous system
      is known as Neuropathic pain. It has been shown that neuropathic pain can be
      treated with the combination of simultaneous transcranial direct current
      stimulation and the generation of the visual illusion that the patient retains
      control of the affected limbs. For persons with neuropathic pain in the lower
      limbs, the visual illusion consists of an image of the patient walking normally.
      Such a visual illusion has classically been generated by using a physical mirror
      and a projector. The objective of this paper is to develop and validate a
      computer-based version of the visual illusion, including Gestural Control. The
      developed system has been validated in a trial and has been successfully
      implanted in daily clinical practice in a reference neurorehabilitation hospital.
      A retrospective statistical analysis shows that the patients treated with the
      computer-based system reduce their pain level significantly more than the
      patients treated with the mirror and projector treatment before the introduction
      of the computer-based version. Furthermore, it also makes possible to bring the
      therapy to the home of the patients, where the treatment can be self-administered
      while still being monitored by the clinical staff.

PMID- 30295626
TI  - Plant Species Identification from Occluded Leaf Images.
AB  - We present an approach to identify the plant species from the contour information
      from occluded leaf image using a database of full plant leaves. Although contour
      based 2D shape matching has been studied extensively in the last couple of
      decades, matching occluded leaves with full leaf databases is an open and little
      worked on problem. Classifying occluded plant leaves is even more challenging
      than full leaf matching because of large variations and complexity of leaf
      structures. Matching an occluded contour with all the full contours in a database
      is an NP-hard problem, so our algorithm is necessarily suboptimal. First, we
      represent the 2D contour points as a beta-Spline curve. Then we extract interest
      points on these curves via the Discrete Contour Evolution (DCE) algorithm. We use
      subgraph matching using the DCE points as graph nodes, which produces a number of
      open curves for each closed leaf contour. Next, we compute the similarity
      transformation parameters (translation, rotation and uniform scaling) for each
      open curve. We then "overlay" each open curve with the inverse similarity
      transformed occluded curve and use the Frechet distance metric to measure the
      quality of the match, retaining the best eta matched curves. Since the Frechet
      metric is cheap to compute but not perfectly correlated with the quality of the
      match, we formulate an energy functional that is well correlated with the quality
      of the match, but is considerably more expensive to compute. The functional uses
      local and global curvature, Shape Context descriptors and String Cut features. We
      minimize this energy functional using a convex-concave relaxation framework. The
      curve among these best eta curves, that has the minimum energy, is considered to
      be the best overall match with the occluded leaf. Experiments on three publicly
      available leaf image database shows that our method is both effective and
      efficient, outperforming other current state-of-the-art methods. Occlusion is
      measured as the percentage of the overall contour (and not leaf area) that is
      missing. We show our algorithm can, even for leaves with a high amounts of
      occlusion (say 50% occlusion), still identify the best full leaf match from the
      databases.

PMID- 30295627
TI  - Secondary Structure and Contact Guided Differential Evolution for Protein
      Structure Prediction.
AB  - Ab initio protein tertiary structure prediction is one of the long-standing
      problems in structural bioinformatics. With the help of the residue-residue
      contact and secondary structure prediction information, the accuracy of ab initio
      structure prediction can be enhanced. In this study, an improved differential
      evolution using the secondary structure and residue-residue contact information
      referred to as SCDE is proposed for protein structure prediction. In SCDE, two
      score models based on the secondary structure and contact information are
      proposed, and two selection strategies, namely, secondary structure-based
      selection strategy and contact-based selection strategy, are designed to guide
      conformation space search. In addition, a probability distribution function is
      designed to balance these two selection strategies. Experimental results on a
      benchmark dataset with 28 proteins and 4 free model targets in CASP12 demonstrate
      that the proposed SCDE is effective and efficient.

PMID- 30295628
TI  - Maximizing Data Transmission Rate for Implantable Devices Over a Single Inductive
      Link: Methodological Review.
AB  - Due to the constantly growing geriatric population and the projected increase of
      the prevalence of chronic diseases that are refractory to drugs, Implantable
      Medical Devices (IMDs) such as neurostimulators, endoscopic capsules, artificial
      retinal prostheses, and brain-machine interfaces are being developed. According
      to many business forecast firms, the IMD market is expected to grow and they are
      subject to much research aiming to overcome the numerous challenges of their
      development. One of these challenges consists of designing a wireless power and
      data transmission system that has high power efficiency, highdata rates, low
      power consumption, and high-robustness against noise. This is in addition to
      minimal design and implementation complexity. This manuscript concerns a
      comprehensive survey of the latest techniques used to power up and communicate
      between an external base station and an IMD. Patient safety considerations
      related to biological, physical, electromagnetic and electromagnetic interference
      concerns for wireless IMDs are also explored. The simultaneous powering and data
      communication techniques using a single inductive link for both power transfer
      and bidirectional data communication; including the various data
      modulation/demodulation techniques; are also reviewed. This review will hopefully
      contribute to the persistent efforts to implement compact reliable IMDs while
      lowering their cost and up-surging their benefits.

PMID- 30295629
TI  - Novel Finite-Time Synchronization Criteria for Inertial Neural Networks With Time
      Delays via Integral Inequality Method.
AB  - In this paper, we are concerned with the finite-time synchronization of a class
      of inertial neural networks with time delays. Without applying some finite-time
      stability theorems, which are widely applied to studying the finite-time
      synchronization for neural networks, by constructing two Lyapunov functions and
      using integral inequality method, two sufficient conditions on the finite-time
      synchronization for a class of inertial neural networks with time delays are
      derived. Considering that the method and research results of the finite-time
      synchronization are different from some existing works, this paper extends the
      works on the finite-time synchronization of neural networks.

PMID- 30295630
TI  - Hypergraph-Induced Convolutional Networks for Visual Classification.
AB  - At present, convolutional neural networks (CNNs) have become popular in visual
      classification tasks because of their superior performance. However, CNN-based
      methods do not consider the correlation of visual data to be classified.
      Recently, graph convolutional networks (GCNs) have mitigated this problem by
      modeling the pairwise relationship in visual data. Real-world tasks of visual
      classification typically must address numerous complex relationships in the data,
      which are not fit for the modeling of the graph structure using GCNs. Therefore,
      it is vital to explore the underlying correlation of visual data. Regarding this
      issue, we propose a framework called the hypergraph-induced convolutional network
      to explore the high-order correlation in visual data during deep neural networks.
      First, a hypergraph structure is constructed to formulate the relationship in
      visual data. Then, the high-order correlation is optimized by a learning process
      based on the constructed hypergraph. The classification tasks are performed by
      considering the high-order correlation in the data. Thus, the convolution of the
      hypergraph-induced convolutional network is based on the corresponding high-order
      relationship, and the optimization on the network uses each data and considers
      the high-order correlation of the data. To evaluate the proposed hypergraph
      induced convolutional network framework, we have conducted experiments on three
      visual data sets: the National Taiwan University 3-D model data set, Princeton
      Shape Benchmark, and multiview RGB-depth object data set. The experimental
      results and comparison in all data sets demonstrate the effectiveness of our
      proposed hypergraph-induced convolutional network compared with the state-of-the
      art methods.

PMID- 30295631
TI  - Early Expression Detection via Online Multi-Instance Learning With Nonlinear
      Extension.
AB  - Video-based facial expression recognition has received substantial attention over
      the past decade, while early expression detection (EED) is still a relatively new
      and challenging problem. The goal of EED is to identify an expression as quickly
      as possible after the expression starts and before it ends. This timely ability
      has many potential applications, ranging from human-computer interaction to
      security. The max-margin early event detector (MMED) is a well-known ranking
      model for early event detection. It can achieve competitive EED performance but
      suffers from several critical limitations: 1) MMED lacks flexibility in
      extracting useful information for segment comparison, which leads to poor
      performance in exploring the ranking relation between segment pairs; 2) the
      training process is slow due to the large number of constraints, and the memory
      requirement is also usually hard to satisfy; and 3) MMED is linear in nature, and
      hence may not be appropriate for data in a nonlinear feature space. To overcome
      these limitations, we propose an online multi-instance learning (MIL) framework
      for EED. In particular, the MIL technique is first introduced to generalize MMED,
      resulting in the proposed MIL-based EED (MIED), which is more general and
      flexible than MMED, since various instance construction and combination
      strategies can be adopted. To accelerate the training process, we reformulate
      MIED in the online setting and develop online multi-instance learning framework
      for EED (OMIED). To further exploit the nonlinear structure of the data
      distribution, we incorporate the kernel methods in OMIED, which results in the
      proposed online kernel multi-instance learning for early expression detection.
      Experiments on two popular and one challenging video-based expression data sets
      demonstrate both the efficiency and effectiveness of the proposed methods.

PMID- 30295632
TI  - LTNN: A Layerwise Tensorized Compression of Multilayer Neural Network.
AB  - An efficient deep learning requires a memory-efficient construction of a neural
      network. This paper introduces a layerwise tensorized formulation of a multilayer
      neural network, called LTNN, such that the weight matrix can be significantly
      compressed during training. By reshaping the multilayer neural network weight
      matrix into a high-dimensional tensor with a low-rank approximation, significant
      network compression can be achieved with maintained accuracy. An according
      layerwise training is developed by a modified alternating least-squares method
      with backward propagation for fine-tuning only. LTNN can provide the state-of-the
      art results on various benchmarks with significant compression. For MNIST
      benchmark, LTNN shows $64 x$ compression rate without accuracy drop. For
      Imagenet12 benchmark, our proposed LTNN achieves $35.84 x$ compression of the
      neural network with around 2% accuracy drop. We have also shown $1.615 x$ faster
      on inference speed than the existing works due to the smaller tensor core ranks.

PMID- 30295633
TI  - Feasibility of Automated Mobility Assessment of Older Adults via an Instrumented
      Cane.
AB  - The current study explored the feasibility of automated characterization of
      functional mobility via an Instrumented Cane System (ICS) within an older adult
      sample of cane users. An off-the-shelf offset cane was instrumented with
      inertial, force, and ultrasound sensors for non-invasive data collection.
      Eighteen patients from a neurological out-patient rehabilitation clinic and nine
      independently-mobile controls participated in standard clinical evaluations of
      mobility using the ICS while under the care of an attending physical therapist.
      Feasibility of the ICS was gauged through two studies. The first demonstrated the
      capability of the ICS to reliably collect meaningful usage metrics, and the
      second provided preliminary support for the discriminability of high and low
      falls risk from system-reported metrics. Specifically, the cane significantly
      differentiated patients and controls (), and a measure of the variation in
      rotational velocity was associated with total scores on the Functional Gait
      Assessment (). These findings may ultimately serve to complement and even extend
      current clinical assessment practices.

PMID- 30295634
TI  - Efficient Brain Tumor Segmentation with Multiscale Two-Pathway-Group Conventional
      Neural Networks.
AB  - Manual segmentation of the brain tumors for cancer diagnosis from MRI images is a
      difficult, tedious and time-consuming task. The accuracy and the robustness of
      brain tumor segmentation, therefore, are crucial for the diagnosis, treatment
      planning, and treatment outcome evaluation. Mostly, the automatic brain tumor
      segmentation methods use hand designed features. Similarly, traditional methods
      of Deep learning such as Convolutional Neural Networks require a large amount of
      annotated data to learn from, which is often difficult to obtain in the medical
      domain. Here we describe a new model Two-Pathway-Group CNN architecture for brain
      tumor segmentation, which exploits local features and global contextual features
      simultaneously. This model enforces equivariance in the Two-Pathway CNN model to
      reduce instabilities and overfitting parameter sharing. Finally, we embed the
      cascade architecture into Two-Pathway-Group CNN in which the output of a basic
      CNN is treated as an additional source and concatenated at the last layer.
      Validation of the model on BRATS2013 and BRATS2015 datasets revealed that
      embedding of a group CNN into a two pathway architecture improved the overall
      performance over the currently published state-of-the-art while computational
      complexity remains attractive.

PMID- 30295635
TI  - Microsimulation Model Using Christiana Care Early Warning System (CEWS) to
      Evaluate Physiological Deterioration.
AB  - While physiological warning signs prior to deterioration events during
      hospitalization have been widely studied, evaluating clinical interventions, such
      as Rapid Response Team (RRT) activations, based on scoring systems remains an
      understudied area. Simulation of physiological deterioration patterns represented
      by scoring systems can facilitate testing different RRT policies without
      disturbing care processes. Christiana Care Early Warning System (CEWS) is a
      scoring system developed at the study hospital to detect the physiological
      warning signs and inform RRT activations. The objective of this study is to
      evaluate CEWS-triggered RRT policies based on patient demographics and policy
      structures. Using retrospective data derived from a subset of Electronic Health
      Records between December 2015 and December 2016 (6,000 patients), we developed a
      microsimulation model with integrated regression analysis to compare RRT policies
      on subpopulations defined by age, gender and comorbidities to find score
      thresholds that result in lowest percent of time spent above critical CEWS
      values. Policies that rely on average scores were more sensitive to threshold
      changes compared to policies that rely on current value and change in CEWS.
      Policy using score threshold 10 provided the lowest percentage of time in
      critical condition for majority of subpopulations. The proposed model is a novel
      framework to simulate individual deterioration patterns and systematically
      evaluate RRT policies based on their impact on health conditions. Our work
      highlights the importance of integration of data-driven models into personalized
      care, and represents a significant opportunity to inform biomedical and health
      informatics research on designing and evaluating EWS-based clinical
      interventions.

PMID- 30295636
TI  - Bi-objective Elite Differential Evolution Algorithm for Multivalued Logic
      Networks.
AB  - In this paper, a novel algorithm called bi-objective elite differential evolution
      (BOEDE) is proposed to optimize multivalued logic (MVL) networks. It is a
      multiobjective algorithm completely different from all previous single-objective
      optimization ones. The two objective functions, error and optimality, are put
      into evaluating the fitness of individuals in evolution simultaneously. BOEDE
      innovatively uses an archive population with different ranks to store elite
      individuals and offsprings. Moreover, a characteristic updating method based on
      this archive structure is designed to produce the parent population. Because of
      the particularity of MVL network problems, the performance of BOEDE to solve them
      is further improved by strictly distinguishing elite solutions and Pareto optimal
      solutions, and by modifying the method of dealing with illegal variables. The
      simulations show that BOEDE can collect a great number of solutions to provide
      decision support for a variety of applications. The comparison results also
      indicate that BOEDE is significantly better than the existing algorithms.

PMID- 30295637
TI  - Spectral Clustering by Joint Spectral Embedding and Spectral Rotation.
AB  - Spectral clustering is an important clustering method widely used for pattern
      recognition and image segmentation. Classical spectral clustering algorithms
      consist of two separate stages: 1) solving a relaxed continuous optimization
      problem to obtain a real matrix followed by 2) applying K-means or spectral
      rotation to round the real matrix (i.e., continuous clustering result) into a
      binary matrix called the cluster indicator matrix. Such a separate scheme is not
      guaranteed to achieve jointly optimal result because of the loss of useful
      information. To obtain a better clustering result, in this paper, we propose a
      joint model to simultaneously compute the optimal real matrix and binary matrix.
      The existing joint model adopts an orthonormal real matrix to approximate the
      orthogonal but nonorthonormal cluster indicator matrix. It is noted that only in
      a very special case (i.e., all clusters have the same number of samples), the
      cluster indicator matrix is an orthonormal matrix multiplied by a real number.
      The error of approximating a nonorthonormal matrix is inevitably large. To
      overcome the drawback, we propose replacing the nonorthonormal cluster indicator
      matrix with a scaled cluster indicator matrix which is an orthonormal matrix. Our
      method is capable of obtaining better performance because it is easy to minimize
      the difference between two orthonormal matrices. Experimental results on
      benchmark datasets demonstrate the effectiveness of the proposed method (called
      JSESR).

PMID- 30295638
TI  - Generative and Discriminative Fuzzy Restricted Boltzmann Machine Learning for
      Text and Image Classification.
AB  - The restricted Boltzmann machine (RBM) is an excellent generative learning model
      for feature extraction. By extending its parameters from real numbers to fuzzy
      ones, we have developed the fuzzy RBM (FRBM) which is demonstrated to possess
      better generative capability than RBM. In this paper, we first propose a
      generative model named Gaussian FRBM (GFRBM) to deal with real-valued inputs.
      Then, motivated by the fact that the discriminative variant of RBM can provide a
      self-contained framework for classification with competitive performance compared
      with some traditional classifiers, we establish the discriminative FRBM (DFRBM)
      and discriminative GFRBM (DGFRBM) that combine both the generative and
      discriminative facility by adding extra neurons next to the input units.
      Specifically, they can be trained into excellent stand-alone classifiers and
      retain outstanding generative capability simultaneously. The experimental results
      including text and image (both clean and noisy) classification indicate that
      DFRBM and DGFRBM outperform discriminative RBM models in terms of reconstruction
      and classification accuracy, and they behave more stable when encountering noisy
      data. Moreover, the proposed learning models show some promising advantages over
      other standard classifiers.

PMID- 30295639
TI  - Finite-Time Synchronization and Hinfinity Synchronization of Multiweighted
      Complex Networks With Adaptive State Couplings.
AB  - In this paper, two kinds of multiweighted and adaptive state coupled complex
      networks (CNs) with or without coupling delays are presented. First, we develop
      the appropriate state feedback controller and adaptive law for the sake of
      guaranteeing that the proposed network models without coupling delays can be
      finite-timely synchronized and Hinfinity synchronized. Furthermore, for the
      multiweighted CNs with coupling delays and adaptive state couplings, some finite
      time synchronization and Hinfinity synchronization criteria are presented by
      choosing the appropriate adaptive law and controllers. Eventually, we give two
      numerical simulations to verify the validity of the theoretical results.

PMID- 30295640
TI  - Probabilistic Rank-One Discriminant Analysis via Collective and Individual
      Variation Modeling.
AB  - Linear discriminant analysis (LDA) is a classical supervised subspace learning
      technique that has wide applications. However, it is designed for vector only,
      which cannot exploit the tensor structures and may lead to suboptimal results
      when dealing with tensorial data. To address this problem, several multilinear
      LDA (MLDA) methods have been proposed to learn the subspaces from tensors. By
      exploiting the tensor structures, they achieve compact subspace representations,
      reduced parameter sizes, and improved robustness against the small sample size
      problem. However, existing MLDA methods do not take data uncertainty into
      account, fail to converge properly, or have to introduce additional tuning
      parameters for good convergence properties. In this paper, we therefore solve
      these limitations by proposing a probabilistic MLDA method for matrix inputs.
      Specifically, we propose a new generative model to incorporate structural
      information into the probabilistic framework, where each observed matrix is
      represented as a linear combination of collective and individual rank-one
      matrices. This provides our method with both the expressiveness of capturing
      discriminative features and nondiscriminative noise, and the capability of
      exploiting the 2-D tensor structures. To overcome the convergence problem of
      existing MLDAs, we develop an EM-type algorithm for parameter estimation, which
      has closed-form solutions with convergence guarantees. Experimental results on
      real-world datasets show the superiority of the proposed method to other
      probabilistic and MLDA variants.

PMID- 30295641
TI  - Emergent Inference of Hidden Markov Models in Spiking Neural Networks Through
      Winner-Take-All.
AB  - Hidden Markov models (HMMs) underpin the solution to many problems in
      computational neuroscience. However, it is still unclear how to implement
      inference of HMMs with a network of neurons in the brain. The existing methods
      suffer from the problem of being nonspiking and inaccurate. Here, we build a
      precise equivalence between the inference equation of HMMs with time-invariant
      hidden variables and the dynamics of spiking winner-take-all (WTA) neural
      networks. We show that the membrane potential of each spiking neuron in the WTA
      circuit encodes the logarithm of the posterior probability of the hidden variable
      in each state, and the firing rate of each neuron is proportional to the
      posterior probability of the HMMs. We prove that the time course of the neural
      firing rate can implement posterior inference of HMMs. Theoretical analysis and
      experimental results show that the proposed WTA circuit can get accurate
      inference results of HMMs.

PMID- 30295642
TI  - Escorting alpha-globin to eNOS: alpha-globin-stabilizing protein paves the way.
AB  - In the vascular wall, endothelial nitric oxide synthase (eNOS) produces NO to
      regulate peripheral vascular resistance, tissue perfusion, and blood pressure. In
      resistance arteries, eNOS couples with alpha-globin and, through chemical
      reactions, modulates NO diffusion needed for vascular smooth muscle relaxation.
      While alpha-globin protein alone is known to be unstable, the mechanisms that
      enable alpha-globin protein expression remain elusive. Here, Lechauve et al.
      report that arterial endothelium expresses alpha hemoglobin-stabilizing protein,
      which acts as a critical chaperone protein for alpha-globin expression and
      vascular function.

PMID- 30295644
TI  - The post-2009 influenza pandemic era: time to revisit antibody immunodominance.
AB  - The current inactivated influenza vaccines rely on the induction of neutralizing
      antibodies against the head domain of the viral hemagglutinin (HA). The HA head
      contains five immunodominant antigenic sites, all of which are subject to
      antigenic drift, thereby limiting vaccine efficacy. Bypassing the immune system's
      tendency to focus on the most variable regions of the HA may be a step toward
      more broadly protective influenza vaccines. However, this requires a better
      understanding of the biological meaning of immunodominance, and of the hierarchy
      between different antigenic sites. In this issue of the JCI, Liu et al.
      determined the immunodominance of the five antigenic sites of the HA head in
      experimentally infected mice, guinea pigs, and ferrets. All three species
      exhibited different preferences for the five sites of the 2009 pandemic H1N1
      strain. Moreover, human subjects exhibited yet a different pattern of
      immunodominance following immunization with the standard inactivated influenza
      vaccine. Together, these results have important implications for influenza
      vaccine design and interpretation of animal models.

PMID- 30295643
TI  - Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial
      infarction.
AB  - Emerging evidence indicates that angiopoietin-2 (Angpt2), a well-recognized
      vascular destabilizing factor, is a biomarker of poor outcome in ischemic heart
      disease. However, its precise role in postischemic cardiovascular remodeling is
      poorly understood. Here, we show that Angpt2 plays multifaceted roles in the
      exacerbation of cardiac hypoxia and inflammation after myocardial ischemia.
      Angpt2 was highly expressed in endothelial cells at the infarct border zone after
      myocardial infarction (MI) or ischemia/reperfusion injury in mice. In the acute
      phase of MI, endothelial-derived Angpt2 antagonized Angpt1/Tie2 signaling, which
      was greatly involved in pericyte detachment, vascular leakage, increased adhesion
      molecular expression, degradation of the glycocalyx and extracellular matrix, and
      enhanced neutrophil infiltration and hypoxia in the infarct border area. In the
      chronic remodeling phase after MI, endothelial- and macrophage-derived Angpt2
      continuously promoted abnormal vascular remodeling and proinflammatory macrophage
      polarization through integrin alpha5beta1 signaling, worsening cardiac hypoxia
      and inflammation. Accordingly, inhibition of Angpt2 either by gene deletion or
      using an anti-Angpt2 blocking antibody substantially alleviated these
      pathological findings and ameliorated postischemic cardiovascular remodeling.
      Blockade of Angpt2 thus has potential as a therapeutic option for ischemic heart
      failure.

PMID- 30295645
TI  - Macrophage migration inhibitory factor mediates metabolic dysfunction induced by
      atypical antipsychotic therapy.
AB  - Atypical antipsychotics are highly effective antischizophrenic medications but
      their clinical utility is limited by adverse metabolic sequelae. We investigated
      whether upregulation of macrophage migration inhibitory factor (MIF) underlies
      the insulin resistance that develops during treatment with the most commonly
      prescribed atypical antipsychotic, olanzapine. Olanzapine monotherapy increased
      BMI and circulating insulin, triglyceride, and MIF concentrations in drug-naive
      schizophrenic patients with normal MIF expression, but not in genotypic low MIF
      expressers. Olanzapine administration to mice increased their food intake and
      hypothalamic MIF expression, which led to activation of the appetite-related AMP
      activated protein kinase and Agouti-related protein pathway. Olanzapine also
      upregulated MIF expression in adipose tissue, which reduced lipolysis and
      increased lipogenic pathways. Increased plasma lipid concentrations were
      associated with abnormal fat deposition in liver and skeletal muscle, which are
      important determinants of insulin resistance. Global MIF-gene deletion protected
      mice from olanzapine-induced insulin resistance, as did intracerebroventricular
      injection of neutralizing anti-MIF antibody, supporting the role of increased
      hypothalamic MIF expression in metabolic dysfunction. These findings uphold the
      potential pharmacogenomic value of MIF genotype determination and suggest that
      MIF may be a tractable target for reducing the metabolic side effects of atypical
      antipsychotic therapy.

PMID- 30295648
TI  - Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of
      Signal Transduction Pathways by Antibody Arrays.
AB  - Cancer patients with an aberrant regulation of the protein phosphorylation
      networks are often treated with the tyrosine kinase inhibitors. Response rates
      approaching 85% are common. Unfortunately, patients often become refractory to
      the treatment by altering their signal transduction pathways. An implementation
      of the expression profiling with microarrays can identify the overall mRNA-level
      changes, and proteomics can identify the overall changes in protein levels or can
      identify the proteins involved, but the activity of the signal transduction
      pathways can only be established by interrogating post-translational
      modifications of the proteins. As a result, the ability to identify whether a
      drug treatment is successful or whether resistance arose, or the ability to
      characterize any alterations in the signaling pathways, is an important clinical
      challenge. Here, we provide a detailed explanation of antibody arrays as a tool
      which can identify system-wide alterations in various post-translational
      modifications (e.g., phosphorylation). One of the advantages of using antibody
      arrays includes their accessibility (an array does not require either an expert
      in proteomics or costly equipment) and speed. The availability of arrays
      targeting a combination of post-translational modifications is the primary
      limitation. In addition, unbiased approaches (phosphoproteomics) may be more
      suitable for the novel discovery, whereas antibody arrays are ideal for the most
      widely characterized targets.

PMID- 30295646
TI  - Endothelial cell alpha-globin and its molecular chaperone alpha-hemoglobin
      stabilizing protein regulate arteriolar contractility.
AB  - Arteriolar endothelial cell-expressed (EC-expressed) alpha-globin binds
      endothelial NOS (eNOS) and degrades its enzymatic product, NO, via dioxygenation,
      thereby lessening the vasodilatory effects of NO on nearby vascular smooth
      muscle. Although this reaction potentially affects vascular physiology, the
      mechanisms that regulate alpha-globin expression and dioxygenase activity in ECs
      are unknown. Without beta-globin, alpha-globin is unstable and cytotoxic,
      particularly in its oxidized form, which is generated by dioxygenation and
      recycled via endogenous reductases. We show that the molecular chaperone alpha
      hemoglobin-stabilizing protein (AHSP) promotes arteriolar alpha-globin expression
      in vivo and facilitates its reduction by eNOS. In Ahsp-/- mice, EC alpha-globin
      was decreased by 70%. Ahsp-/- and Hba1-/- mice exhibited similar evidence of
      increased vascular NO signaling, including arteriolar dilation, blunted alpha1
      adrenergic vasoconstriction, and reduced blood pressure. Purified alpha-globin
      bound eNOS or AHSP, but not both together. In ECs in culture, eNOS or AHSP
      enhanced alpha-globin expression posttranscriptionally. However, only AHSP
      prevented oxidized alpha-globin precipitation in solution. Finally, eNOS reduced
      AHSP-bound alpha-globin approximately 6-fold faster than did the major
      erythrocyte hemoglobin reductases (cytochrome B5 reductase plus cytochrome B5).
      Our data support a model whereby redox-sensitive shuttling of EC alpha-globin
      between AHSP and eNOS regulates EC NO degradation and vascular tone.

PMID- 30295649
TI  - Dynamic Adhesion Assay for the Functional Analysis of Anti-adhesion Therapies in
      Inflammatory Bowel Disease.
AB  - Gut homing of immune cells is important for the pathogenesis of inflammatory
      bowel diseases (IBD). Integrin-dependent cell adhesion to addressins is a crucial
      step in this process and therapeutic strategies interfering with adhesion have
      been successfully established. The anti-alpha4beta7 integrin antibody,
      vedolizumab, is used for the clinical treatment of Crohn's disease (CD) and
      ulcerative colitis (UC) and further compounds are likely to follow. The details
      of the adhesion procedure and the action mechanisms of anti-integrin antibodies
      are still unclear in many regards due to the limited available techniques for the
      functional research in this field. Here, we present a dynamic adhesion assay for
      the functional analysis of human cell adhesion under flow conditions and the
      impact of anti-integrin therapies in the context of IBD. It is based on the
      perfusion of primary human cells through addressin-coated ultrathin glass
      capillaries with real-time microscopic analysis. The assay offers a variety of
      opportunities for refinements and modifications and holds potentials for
      mechanistic discoveries and translational applications.

PMID- 30295650
TI  - CRISPR/Cas9 Gene Editing to Make Conditional Mutants of Human Malaria Parasite P.
      falciparum.
AB  - Malaria is a significant cause of morbidity and mortality worldwide. This
      disease, which primarily affects those living in tropical and subtropical
      regions, is caused by infection with Plasmodium parasites. The development of
      more effective drugs to combat malaria can be accelerated by improving our
      understanding of the biology of this complex parasite. Genetic manipulation of
      these parasites is key to understanding their biology; however, historically the
      genome of P. falciparum has been difficult to manipulate. Recently, CRISPR/Cas9
      genome editing has been utilized in malaria parasites, allowing for easier
      protein tagging, generation of conditional protein knockdowns, and deletion of
      genes. CRISPR/Cas9 genome editing has proven to be a powerful tool for advancing
      the field of malaria research. Here, we describe a CRISPR/Cas9 method for
      generating glmS-based conditional knockdown mutants in P. falciparum. This method
      is highly adaptable to other types of genetic manipulations, including protein
      tagging and gene knockouts.

PMID- 30295647
TI  - DeltaNp63-driven recruitment of myeloid-derived suppressor cells promotes
      metastasis in triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) is particularly aggressive, with enhanced
      incidence of tumor relapse, resistance to chemotherapy, and metastases. As the
      mechanistic basis for this aggressive phenotype is unclear, treatment options are
      limited. Here, we showed an increased population of myeloid-derived
      immunosuppressor cells (MDSCs) in TNBC patients compared with non-TNBC patients.
      We found that high levels of the transcription factor DeltaNp63 correlate with an
      increased number of MDSCs in basal TNBC patients, and that DeltaNp63 promotes
      tumor growth, progression, and metastasis in human and mouse TNBC cells.
      Furthermore, we showed that MDSC recruitment to the primary tumor and metastatic
      sites occurs via direct DeltaNp63-dependent activation of the chemokines CXCL2
      and CCL22. CXCR2/CCR4 inhibitors reduced MDSC recruitment, angiogenesis, and
      metastasis, highlighting a novel treatment option for this subset of TNBC
      patients. Finally, we found that MDSCs secrete prometastatic factors such as MMP9
      and chitinase 3-like 1 to promote TNBC cancer stem cell function, thereby
      identifying a nonimmunologic role for MDSCs in promoting TNBC progression. These
      findings identify a unique crosstalk between DeltaNp63+ TNBC cells and MDSCs that
      promotes tumor progression and metastasis, which could be exploited in future
      combined immunotherapy/chemotherapy strategies for TNBC patients.

PMID- 30295651
TI  - Anogenital Distance and Perineal Measurements of the Pelvic Organ Prolapse (POP)
      Quantification System.
AB  - Anogenital distance (AGD) is a sexually dimorphic attribute, twice longer in
      males than in females, and a marker of intrauterine hormonal environment.
      Interest in AGD measurements is increasing due to mounting evidence on their
      potential clinical implications. A parallel set of perineal measurements, the
      Pelvic Organ Prolapse Quantification System (POP-Q), include similar, but not
      exactly the same, landmarks: the perineal body (PB) and the genital hiatus (GH)
      lengths. However, clinical reproducibility of both perineal measurements and
      their usefulness to describe perineal anthropometry needs to be elucidated. To
      our knowledge, there is no publication in video format showing the methodology of
      these measurements. The main objective of this work is to show how to properly
      perform perineal anthropometry, including measurements of the AGD in its two
      variants [anoclitoral (AGDAC) and anofourchette (AGDAF)], genital hiatus (GH) and
      perineal body (PB). Moreover, we explored if there were differences in these
      measurements in women with and without Pelvic Organ Prolapse (POP). We research
      whether the anthropometric characteristics of the perineum, such as AGD (which is
      determined prenatally), may be altered in these women and be an independent
      etiological factor for pelvic floor dysfunction. We show two different ways of
      measuring perineal lengths, as they might be quite comparable. Our suggestion is
      that unifying perineal measurements could be useful for clinical and biomedical
      investigation. More studies are needed in order to compare GH and PB measurements
      and its AGD counterparts to analyze which procedures are more reproducible with
      less intra and interobserver variability.

PMID- 30295652
TI  - Olfactory Context Dependent Memory: Direct Presentation of Odorants.
AB  - Information is retrieved more effectively when the retrieval occurs in the same
      context as that in which the information was first encoded. This is termed
      context dependent memory (CDM). One category of cues that have been shown to
      effectively produce CDM effects are odors. However, it is unclear what the
      boundary conditions of these CDM effects are. In particular, given that olfaction
      has been called an implicit sense, it is possible that odors are only effective
      mnemonic cues when they are presented in the background. This assertion seems
      even more likely given that previous research has shown odors to be poor cues
      during paired associate memory tests, where odors are in the focus of attention
      as mnemonic cues for other information. In order to determine whether odors are
      only effective contextual mnemonic cues when presented outside the central focus
      of an observer, an olfactory CDM experiment was performed in which odorants were
      presented directly, rather than ambiently. Direct presentation was accomplished
      with the aid of an olfactometer. The olfactometer not only allows for direct
      presentation of odorants, but provides other methodological benefits, including
      the allowance of trial by trial manipulations of odorant presentations and,
      relatedly, time-specific releases of odorants. The presence of the same odor
      during both encoding and retrieval enhanced memory performance, regardless of
      whether the odor was presented ambiently or directly. This finding can serve as a
      basis for future olfactory CDM research which can utilize the benefits of direct
      presentation.

PMID- 30295653
TI  - An Available Technique for Preparation of New Cast MnCuNiFeZnAl Alloy with
      Superior Damping Capacity and High Service Temperature.
AB  - Manganese (Mn)-copper (Cu)-based alloys have been found to have damping capacity
      and can be used to reduce harmful vibrations and noise effectively. M2052 (Mn
      20Cu-5Ni-2Fe, at%) is an important branch of Mn-Cu-based alloys, which possesses
      both excellent damping capacity and processability. In recent decades, lots of
      studies have been carried out on the performance optimization of M2052, improving
      the damping capacity, mechanical properties, corrosion resistance, and service
      temperature, etc. The major methods of performance optimization are alloying,
      heat treatment, pretreatment, and different ways of molding etc., among which
      alloying, as well as adopting a reasonable heat treatment, is the simplest and
      most effective method to obtain perfect and comprehensive performance. To obtain
      the M2052 alloy with excellent performance for casting molding, we propose to add
      Zn and Al to the MnCuNiFe alloy matrix and use a variety of heat treatment
      methods for a comparison in the microstructure, damping capacity, and service
      temperature. Thus, a new type of cast-aged Mn-22.68Cu-1.89Ni-1.99Fe-1.70Zn-6.16Al
      (at.%) alloy with superior damping capacity and high service temperature is
      obtained by an optimized heat treatment method. Compared with the forging
      technique, cast molding is simpler and more efficient, and the damping capacity
      of this as-cast alloy is excellent. Therefore, there is a suitable reason to
      think that it is a good choice for engineering applications.

PMID- 30295654
TI  - An Efficient Strategy for Generating Tissue-specific Binary Transcription Systems
      in Drosophila by Genome Editing.
AB  - Binary transcription systems are powerful genetic tools widely used for
      visualizing and manipulating cell fate and gene expression in specific groups of
      cells or tissues in model organisms. These systems contain two components as
      separate transgenic lines. A driver line expresses a transcriptional activator
      under the control of tissue-specific promoters/enhancers, and a reporter/effector
      line harbors a target gene placed downstream to the binding site of the
      transcription activator. Animals harboring both components induce tissue-specific
      transactivation of a target gene expression. Precise spatiotemporal expression of
      the gene in targeted tissues is critical for unbiased interpretation of cell/gene
      activity. Therefore, developing a method for generating exclusive cell/tissue
      specific driver lines is essential. Here we present a method to generate highly
      tissue-specific targeted expression system by employing a "Clustered Regularly
      Interspaced Short Palindromic Repeat/CRISPR-associated" (CRISPR/Cas)-based genome
      editing technique. In this method, the endonuclease Cas9 is targeted by two
      chimeric guide RNAs (gRNA) to specific sites in the first coding exon of a gene
      in the Drosophila genome to create double-strand breaks (DSB). Subsequently,
      using an exogenous donor plasmid containing the transactivator sequence, the cell
      autonomous repair machinery enables homology-directed repair (HDR) of the DSB,
      resulting in precise deletion and replacement of the exon with the transactivator
      sequence. The knocked-in transactivator is expressed exclusively in cells where
      the cis-regulatory elements of the replaced gene are functional. The detailed
      step-by-step protocol presented here for generating a binary transcriptional
      driver expressed in Drosophila fgf/branchless-producing epithelial/neuronal cells
      can be adopted for any gene- or tissue-specific expression.

PMID- 30295655
TI  - Highly Sensitive and Quantitative Detection of Proteins and Their Isoforms by
      Capillary Isoelectric Focusing Method.
AB  - Immunoblotting has become a routine technique in many laboratories for protein
      characterization from biological samples. The following protocol provides an
      alternative strategy, capillary isoelectric focusing (cIEF), with many advantages
      compared to conventional immunoblotting. This is an antibody-based, automated,
      rapid, and quantitative method in which a complete western blotting procedure
      takes place inside an ultrathin capillary. This technique does not require a gel
      to transfer to a membrane, stripping of blots, or x-ray films, which are
      typically required for conventional immunoblotting. Here, proteins are separated
      according to their charge (isoelectric point; pI), using less than a microliter
      (400 nL) of total protein lysate. After electrophoresis, proteins are immobilized
      onto the capillary walls by ultraviolet light treatment, followed by primary and
      secondary (horseradish peroxidase (HRP) conjugated) antibody incubation, whose
      binding is detected through enhanced chemiluminescence (ECL), generating a light
      signal that can be captured and recorded by a charge-coupled device (CCD) camera.
      The digital image can be analyzed and quantified (peak area) using software. This
      high throughput procedure can handle 96 samples at a time; is highly sensitive,
      with protein detection in the picogram range; and produces highly reproducible
      results because of automation. All of these aspects are extremely valuable when
      the quantity of samples (e.g., tissue samples and biopsies) is a limiting factor.
      The technique has wider applications as well, including screening of drugs or
      antibodies, biomarker discovery, and diagnostic purposes.

PMID- 30295656
TI  - Application of Design Aspects in Uniaxial Loading Machine Development.
AB  - In terms of accurate and precise mechanical testing, machines run the continuum.
      Whereas commercial platforms offer excellent accuracy, they can be cost
      prohibitive, often priced in the $100,000 - $200,000 price range. At the other
      extreme are stand-alone manual devices that often lack repeatability and accuracy
      (e.g., a manual crank device). However, if a single use is indicated, it is over
      engineering to design and machine something overly elaborate. Nonetheless, there
      are occasions where machines are designed and built in-house to accomplish a
      motion not attainable with the existing machines in the laboratory. Described in
      detail here is one such device. It is a loading platform that enables pure
      uniaxial loading. Standard loading machines typically are biaxial in that linear
      loading occurs along the axis and rotary loading occurs about the axis. During
      testing with these machines, a load is applied to one end of the specimen while
      the other end remains fixed. These systems are not capable of conducting pure
      axial testing in which tension/compression is applied equally to the specimen
      ends. The platform developed in this paper enables the equal and opposite loading
      of specimens. While it can be used for compression, here the focus is on its use
      in pure tensile loading. The device incorporates commercial load cells and
      actuators (movers) and, as is the case with machines built in-house, a frame is
      machined to hold the commercial parts and fixtures for testing.

PMID- 30295658
TI  - 'Boden Food Plate': Novel Interactive Web-based Method for the Assessment of
      Dietary Intake.
AB  - Different methods can be used in research to assess dietary intake, many of which
      are still paper-based. Written estimated food diaries are often utilized in
      clinical trials, despite being a burden for both study participants and
      researchers. This method requires participant literacy, it is time consuming,
      labor intensive, and can easily lead to under-reporting. With advancements in
      technology, there is a growing interest in electronic diaries that automate the
      dietary assessment process. These are focused on improving accuracy, reducing
      both time and cost and providing users with a visual and more enjoyable
      experience. The methodology presented here aimed to validate the 'Boden Food
      Plate', a novel web-based platform for self-recording of food and drink items,
      compared to a traditional estimated food diary. The application was also rated on
      a satisfaction scale by study participants using a paper-based questionnaire.
      Sixty-seven participants completed the dietary measures on both the three-day
      electronic and paper food diaries. For the analysis, only dietary data completed
      at both study time points (baseline and week six) was utilized. Despite small
      mean differences between dietary data collection methods, Bland Altman analysis
      showed fairly wide 95% limits of agreement between the electronic platform and
      the written estimated food diary and there were few cases which did not fall
      within the 95% confidence intervals. Overall, participants found the electronic
      food diary to be more fun than the paper method and as easy to use as hard copy
      diaries. The new platform has potential as a self-recording tool for the
      collection of dietary data, particularly when utilized in clinical trial
      settings. However, further validation studies are needed to improve the validity
      of this novel electronic dietary data collection tool.

PMID- 30295659
TI  - Isolation and Fluorescence Imaging for Single-particle Reconstruction of
      Chlamydomonas Centrioles.
AB  - Centrioles are large macromolecular assemblies important for the proper execution
      of fundamental cell biological processes such as cell division, cell motility, or
      cell signaling. The green algae Chlamydomonas reinhardtii has proven to be an
      insightful model in the study of centriole architecture, function, and protein
      composition. Despite great advances toward understanding centriolar architecture,
      one of the current challenges is to determine the precise localization of
      centriolar components within structural regions of the centriole in order to
      better understand their role in centriole biogenesis. A major limitation lies in
      the resolution of fluorescence microscopy, which complicates the interpretation
      of protein localization in this organelle with dimensions close to the
      diffraction limit. To tackle this question, we are providing a method to purify
      and image a large number of C. reinhardtii centrioles with different orientations
      using super-resolution microscopy. This technique allows further processing of
      data through fluorescent single-particle averaging (Fluo-SPA) owing to the large
      number of centrioles acquired. Fluo-SPA generates averages of stained C.
      reinhardtii centrioles in different orientations, thus facilitating the
      localization of distinct proteins in centriolar sub-regions. Importantly, this
      method can be applied to image centrioles from other species or other large
      macromolecular assemblies.

PMID- 30295657
TI  - Autonomic Function Following Concussion in Youth Athletes: An Exploration of
      Heart Rate Variability Using 24-hour Recording Methodology.
AB  - Participation in organized sports makes a significant contribution to youth
      development, but places youth at a higher risk for sustaining a concussion. To
      date, return-to-activity decision-making has been anchored in the monitoring of
      self-reported concussion symptoms and neurocognitive testing. However, multi
      modal assessments that corroborate objective physiological measures with
      traditional subjective symptom reporting are needed and can be valuable. Heart
      rate variability (HRV) is a non-invasive physiological indicator of the autonomic
      nervous system, capturing the reciprocal interplay between the sympathetic and
      parasympathetic nervous systems. There is a dearth of literature exploring the
      effect of concussion on HRV in youth athletes, and developmental differences
      preclude the application of adult findings to a pediatric population. Further,
      the current state of HRV methodology has primarily included short-term (5-15 min)
      recordings, by using resting state or short-term physical exertion testing to
      elucidate changes following concussion. The novelty in utilizing a 24 h recording
      methodology is that it has the potential to capture natural variation in
      autonomic function, directly related to the activities a youth athlete performs
      on a regular basis. Within a prospective, longitudinal research setting, this
      novel approach to quantifying autonomic function can provide important
      information regarding the recovery trajectory, alongside traditional self-report
      symptom measures. Our objectives regarding a 24 h recording methodology were to
      (1) evaluate the physiological effects of a concussion in youth athletes, and (2)
      describe the trajectory of physiological change, while considering the resolution
      of self-reported post-concussion symptoms. To achieve these objectives, non
      invasive sensor technology was implemented. The raw beat-to-beat time intervals
      captured can be transformed to derive time domain and frequency domain measures,
      which reflect an individual's ability to adapt and be flexible to their ever
      changing environment. By using non-invasive heart rate technology, autonomic
      function can be quantified outside of a traditional controlled research setting.

PMID- 30295661
TI  - Expression of Cementitious Pore Solution and the Analysis of Its Chemical
      Composition and Resistivity Using X-ray Fluorescence.
AB  - The goal of this method is to determine the chemical composition and electrical
      resistivity of cementitious pore solution expressed from a fresh paste sample.
      The pore solution is expressed from a fresh paste sample using a pressurized
      nitrogen gas system. The pore solution is then immediately transferred to a
      syringe to minimize evaporation and carbonation. After that, assembled testing
      containers are used for the X-ray fluorescence (XRF) measurement. These
      containers consist of two concentric plastic cylinders and a polypropylene film
      which seals one of the two open sides. The pore solution is added into the
      container immediately prior to the XRF measurement. The XRF is calibrated to
      detect the main ionic species in the pore solution, in particular, sodium (Na+),
      potassium (K+), calcium (Ca2+), and sulfide (S2-), to calculate sulfate (SO42-)
      using stoichiometry. The hydroxides (OH-) can be calculated from a charge
      balance. To calculate the electrical resistivity of the solution, the
      concentrations of the main ionic species and a model by Snyder et al. are used.
      The electrical resistivity of the pore solution can be used, along with the
      electrical resistivity of concrete, to determine the formation factor of
      concrete. XRF is a potential alternative to current methods to determine the
      composition of pore solution, which can provide benefits in terms of reduction in
      time and costs.

PMID- 30295660
TI  - The Combined Use of Transcranial Direct Current Stimulation and Robotic Therapy
      for the Upper Limb.
AB  - Neurologic disorders such as stroke and cerebral palsy are leading causes of long
      term disability and can lead to severe incapacity and restriction of daily
      activities due to lower and upper limb impairments. Intensive physical and
      occupational therapy are still considered main treatments, but new adjunct
      therapies to standard rehabilitation that may optimize functional outcomes are
      being studied. Transcranial direct current stimulation (tDCS) is a noninvasive
      brain stimulation technique that polarizes underlying brain regions through the
      application of weak direct currents through electrodes on the scalp, modulating
      cortical excitability. Increased interest in this technique can be attributed to
      its low cost, ease of use, and effects on human neural plasticity. Recent
      research has been performed to determine the clinical potential of tDCS in
      diverse conditions such as depression, Parkinson's disease, and motor
      rehabilitation after stroke. tDCS helps enhance brain plasticity and seems to be
      a promising technique in rehabilitation programs. A number of robotic devices
      have been developed to assist in the rehabilitation of upper limb function after
      stroke. The rehabilitation of motor deficits is often a long process requiring
      multidisciplinary approaches for a patient to achieve maximum independence. These
      devices do not intend to replace manual rehabilitation therapy; instead, they
      were designed as an additional tool to rehabilitation programs, allowing
      immediate perception of results and tracking of improvements, thus helping
      patients to stay motivated. Both tDSC and robot-assisted therapy are promising
      add-ons to stroke rehabilitation and target the modulation of brain plasticity,
      with several reports describing their use to be associated with conventional
      therapy and the improvement of therapeutic outcomes. However, more recently, some
      small clinical trials have been developed that describe the associated use of
      tDCS and robot-assisted therapy in stroke rehabilitation. In this article, we
      describe the combined methods used in our institute for improving motor
      performance after stroke.

PMID- 30295662
TI  - Fabrication of Three-Dimensional Graphene-Based Polyhedrons via Origami-Like Self
      Folding.
AB  - The assembly of two-dimensional (2D) graphene into three-dimensional (3D)
      polyhedral structures while preserving the graphene's excellent inherent
      properties has been of great interest for the development of novel device
      applications. Here, fabrication of 3D, microscale, hollow polyhedrons (cubes)
      consisting of a few layers of 2D graphene or graphene oxide sheets via an origami
      like self-folding process is described. This method involves the use of polymer
      frames and hinges, and aluminum oxide/chromium protection layers that reduce
      tensile, spatial, and surface tension stresses on the graphene-based membranes
      when the 2D nets are transformed into 3D cubes. The process offers control of the
      size and shape of the structures as well as parallel production. In addition,
      this approach allows the creation of surface modifications by metal patterning on
      each face of the 3D cubes. Raman spectroscopy studies show the method allows the
      preservation of the intrinsic properties of the graphene-based membranes,
      demonstrating the robustness of our method.

PMID- 30295663
TI  - Negative Additive Manufacturing of Complex Shaped Boron Carbides.
AB  - Boron carbide (B4C) is one of the hardest materials in existence. However, this
      attractive property also limits its machineability into complex shapes for high
      wear, high hardness, and lightweight material applications such as armors. To
      overcome this challenge, negative additive manufacturing (AM) is employed to
      produce complex geometries of boron carbides at various length scales. Negative
      AM first involves gelcasting a suspension into a 3D-printed plastic mold. The
      mold is then dissolved away, leaving behind a green body as a negative copy.
      Resorcinol-formaldehyde (RF) is used as a novel gelling agent because unlike
      traditional hydrogels, there is little to no shrinkage, which allows for
      extremely complex molds to be used. Furthermore, this gelling agent can be
      pyrolyzed to leave behind ~50 wt% carbon, which is a highly effective sintering
      aid for B4C. Due to this highly homogenous distribution of in situ carbon within
      the B4C matrix, less than 2% porosity can be achieved after sintering. This
      protocol highlights in detail the methodology for creating near fully dense boron
      carbide parts with highly complex geometries.

PMID- 30295664
TI  - Transcranial Direct Current Stimulation (tDCS) in Mice.
AB  - Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation
      technique proposed as an alternative or complementary treatment for several
      neuropsychiatric diseases. The biological effects of tDCS are not fully
      understood, which is in part explained due to the difficulty in obtaining human
      brain tissue. This protocol describes a tDCS mouse model that uses a chronically
      implanted electrode allowing the study of the long-lasting biological effects of
      tDCS. In this experimental model, tDCS changes the cortical gene expression and
      offers a prominent contribution to the understanding of the rationale for its
      therapeutic use.

PMID- 30295665
TI  - Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical
      Epigenetic Modifiers.
AB  - Regulation of chromatin compaction is an important process that governs gene
      expression in higher eukaryotes. Although chromatin compaction and gene
      expression regulation are commonly disrupted in many diseases, a locus-specific,
      endogenous, and reversible method to study and control these mechanisms of action
      has been lacking. To address this issue, we have developed and characterized
      novel gene-regulating bifunctional molecules. One component of the bifunctional
      molecule binds to a DNA-protein anchor so that it will be recruited to an allele
      specific locus. The other component engages endogenous cellular chromatin
      modifying machinery, recruiting these proteins to a gene of interest. These small
      molecules, called chemical epigenetic modifiers (CEMs), are capable of
      controlling gene expression and the chromatin environment in a dose-dependent and
      reversible manner. Here, we detail a CEM approach and its application to decrease
      gene expression and histone tail acetylation at a Green Fluorescent Protein (GFP)
      reporter located at the Oct4 locus in mouse embryonic stem cells (mESCs). We
      characterize the lead CEM (CEM23) using fluorescent microscopy, flow cytometry,
      and chromatin immunoprecipitation (ChIP), followed by a quantitative polymerase
      chain reaction (qPCR). While the power of this system is demonstrated at the Oct4
      locus, conceptually, the CEM technology is modular and can be applied in other
      cell types and at other genomic loci.

PMID- 30295666
TI  - Synthesis and Characterization of Placental Chondroitin Sulfate A (plCSA)
      Targeting Lipid-Polymer Nanoparticles.
AB  - An effective cancer therapeutic method reduces and eliminates tumors with minimal
      systemic toxicity. Actively targeting nanoparticles offer a promising approach to
      cancer therapy. The glycosaminoglycan placental chondroitin sulfate A (plCSA) is
      expressed on a wide range of cancer cells and placental trophoblasts, and
      malarial protein VAR2CSA can specifically bind to plCSA. A reported placental
      chondroitin sulfate A binding peptide (plCSA-BP), derived from malarial protein
      VAR2CSA, can also specifically bind to plCSA on cancer cells and placental
      trophoblasts. Hence, plCSA-BP-conjugated nanoparticles could be used as a tool
      for targeted drug delivery to human cancers and placental trophoblasts. In this
      protocol, we describe a method to synthesize plCSA-BP-conjugated lipid-polymer
      nanoparticles loaded with doxorubicin (plCSA-DNPs); the method consists of a
      single sonication step and bioconjugate techniques. In addition, several methods
      for characterizing plCSA-DNPs, including determining their physicochemical
      properties and cellular uptake by placental choriocarcinoma (JEG3) cells, are
      described.

PMID- 30295667
TI  - Simultaneous Cryosectioning of Multiple Rodent Brains.
AB  - Histology and immunohistochemistry are routine methods of analysis to visualize
      microscopic anatomy and localize proteins within biological tissue. In
      neuroscience, as well as a plethora of other scientific fields, these techniques
      are used. Immunohistochemistry can be done on slide mounted tissue or free
      floating sections. Preparing slide-mounted samples is a time intensive process.
      The following protocol for a technique, called the Megabrain, reduced the time
      taken to cryosection and mount brain tissue by up to 90% by combining multiple
      brains into a single frozen block. Furthermore, this technique reduced
      variability seen between staining rounds, in a large histochemical study. The
      current technique has been optimized for using rodent brain tissue in downstream
      immunohistochemical analyses; however, it can be applied to different scientific
      fields that use cryosectioning.

PMID- 30295668
TI  - Identification, Histological Characterization, and Dissection of Mouse Prostate
      Lobes for In Vitro 3D Spheroid Culture Models.
AB  - Genetically engineered mouse models (GEMMs) serve as effective pre-clinical
      models for investigating most types of human cancers, including prostate cancer
      (PCa). Understanding the anatomy and histology of the mouse prostate is important
      for the efficient use and proper characterization of such animal models. The
      mouse prostate has four distinct pairs of lobes, each with their own
      characteristics. This article demonstrates the proper method of dissection and
      identification of mouse prostate lobes for disease analysis. Post-dissection, the
      prostate cells can be further cultured in vitro for mechanistic understanding.
      Since mouse prostate primary cells tend to lose their normal characteristics when
      cultured in vitro, we outline here a method for isolating the cells and growing
      them as 3D spheroid cultures, which is effective for preserving the physiological
      characteristics of the cells. These 3D cultures can be used for analyzing cell
      morphology and behavior in near-physiological conditions, investigating altered
      levels and localizations of key proteins and pathways involved in the development
      and progression of a disease, and looking at responses to drug treatments.

PMID- 30295669
TI  - A Metadata Extraction Approach for Clinical Case Reports to Enable Advanced
      Understanding of Biomedical Concepts.
AB  - Clinical case reports (CCRs) are a valuable means of sharing observations and
      insights in medicine. The form of these documents varies, and their content
      includes descriptions of numerous, novel disease presentations and treatments.
      Thus far, the text data within CCRs is largely unstructured, requiring
      significant human and computational effort to render these data useful for in
      depth analysis. In this protocol, we describe methods for identifying metadata
      corresponding to specific biomedical concepts frequently observed within CCRs. We
      provide a metadata template as a guide for document annotation, recognizing that
      imposing structure on CCRs may be pursued by combinations of manual and automated
      effort. The approach presented here is appropriate for organization of concept
      related text from a large literature corpus (e.g., thousands of CCRs) but may be
      easily adapted to facilitate more focused tasks or small sets of reports. The
      resulting structured text data includes sufficient semantic context to support a
      variety of subsequent text analysis workflows: meta-analyses to determine how to
      maximize CCR detail, epidemiological studies of rare diseases, and the
      development of models of medical language may all be made more realizable and
      manageable through the use of structured text data.

PMID- 30295670
TI  - Manufacturing Abdominal Aorta Hydrogel Tissue-Mimicking Phantoms for Ultrasound
      Elastography Validation.
AB  - Ultrasound (US) elastography, or elasticity imaging, is an adjunct imaging
      technique that utilizes sequential US images of soft tissues to measure the
      tissue motion and infer or quantify the underlying biomechanical characteristics.
      For abdominal aortic aneurysms (AAA), biomechanical properties such as changes in
      the tissue's elastic modulus and estimates of the tissue stress may be essential
      for assessing the need for the surgical intervention. Abdominal aortic aneurysms
      US elastography could be a useful tool to monitor AAA progression and identify
      changes in biomechanical properties characteristic of high-risk patients. A
      preliminary goal in the development of an AAA US elastography technique is the
      validation of the method using a physically relevant model with known material
      properties. Here we present a process for the production of AAA tissue-mimicking
      phantoms with physically relevant geometries and spatially modulated material
      properties. These tissue phantoms aim to mimic the US properties, material
      modulus, and geometry of the abdominal aortic aneurysms. Tissue phantoms are made
      using a polyvinyl alcohol cryogel (PVA-c) and molded using 3D printed parts
      created using computer aided design (CAD) software. The modulus of the phantoms
      is controlled by altering the concentration of PVA-c and by changing the number
      of freeze-thaw cycles used to polymerize the cryogel. The AAA phantoms are
      connected to a hemodynamic pump, designed to deform the phantoms with the
      physiologic cyclic pressure and flows. Ultra sound image sequences of the
      deforming phantoms allowed for the spatial calculation of the pressure normalized
      strain and the identification of mechanical properties of the vessel wall.
      Representative results of the pressure normalized strain are presented.

PMID- 30295671
TI  - A de novo transcriptome assembly of the zebra bullhead shark, Heterodontus zebra.
AB  - Although cartilaginous fishes have played crucial roles in various fields,
      including evolutionary biology, marine ecology, bioresources, and aquarium
      exhibitions, molecular information for these species is poorly available. The
      present study reports a transcriptome assembly from an embryo of the zebra
      bullhead shark (Heterodontus zebra), produced by paired-end RNA sequencing.
      Transcriptome data is generated with a de novo transcriptome assembler, Trinity.
      Amino acid sequences are predicted from the assemblies, using TransDecoder.
      Because cartilaginous fishes serve as the outgroup of bony vertebrates, the data
      would contribute to comparative analyses of a various biological fields. In
      addition, this study would be useful for conservation biology, such as
      transcriptome-based population genetics.

PMID- 30295672
TI  - Comprehensive identification of peptides in tandem mass spectra using an
      efficient open search engine.
AB  - We present a sequence-tag-based search engine, Open-pFind, to identify peptides
      in an ultra-large search space that includes coeluting peptides, unexpected
      modifications and digestions. Our method detects peptides with higher precision
      and speed than seven other search engines. Open-pFind identified 70-85% of the
      tandem mass spectra in four large-scale datasets and 14,064 proteins, each
      supported by at least two protein-unique peptides, in a human proteome dataset.

PMID- 30295673
TI  - Nondestructive, base-resolution sequencing of 5-hydroxymethylcytosine using a DNA
      deaminase.
AB  - Here we present APOBEC-coupled epigenetic sequencing (ACE-seq), a bisulfite-free
      method for localizing 5-hydroxymethylcytosine (5hmC) at single-base resolution
      with low DNA input. The method builds on the observation that AID/APOBEC family
      DNA deaminase enzymes can potently discriminate between cytosine modification
      states and exploits the non-destructive nature of enzymatic, rather than
      chemical, deamination. ACE-seq yielded high-confidence 5hmC profiles with at
      least 1,000-fold less DNA input than conventional methods. Applying ACE-seq to
      generate a base-resolution map of 5hmC in tissue-derived cortical excitatory
      neurons, we found that 5hmC was almost entirely confined to CG dinucleotides. The
      whole-genome map permitted cytosine, 5-methylcytosine (5mC) and 5hmC to be parsed
      and revealed genomic features that diverged from global patterns, including
      enhancers and imprinting control regions with high and low 5hmC/5mC ratios,
      respectively. Enzymatic deamination overcomes many challenges posed by bisulfite
      based methods, thus expanding the scope of epigenome profiling to include scarce
      samples and opening new lines of inquiry regarding the role of cytosine
      modifications in genome biology.

PMID- 30295675
TI  - Embryonic transcriptome sequencing of the ocellate spot skate Okamejei kenojei.
AB  - Chondrichthyans (cartilaginous fishes) exhibit highly variable reproductive
      styles, categorized as viviparity and oviparity. Among these, species with
      oviparity provide an enormous potential of molecular experimentation with stable
      sample supply which does not demand the sacrifices of live mothers. Cartilaginous
      fishes are divided into two subclasses, chimaeras (Holocephali) and elasmobranchs
      (Elasmobranchii), and the latter consists of two monophyletic groups, Batoidea
      (rays, skates and torpedoes) and Selachimorpha (sharks). Here we report
      transcriptome assemblies of the ocellate spot skate Okamejei kenojei, produced by
      strand-specific RNA-seq of its embryonic tissues. We obtained a total of 325
      million illumina short reads from libraries prepared using four different tissue
      domains and assembled them all together. Our assembly result confirmed the
      species authenticity and high continuity of contig sequences. Also, assessment of
      its coverage of pre-selected one-to-one orthologs supported high diversity of
      transcripts in the assemblies. Our products are expected to provide a basis of
      comparative molecular studies encompassing other chondrichthyan species with
      emerging genomic and transcriptomic sequence information.

PMID- 30295676
TI  - Role of food-drug interactions in neurological and psychological diseases.
AB  - Given that foods and nutrients have been shown to influence the pharmacokinetics
      of drugs, drugs may cause changes in the nutritional status of patients and their
      response to a given drug. Food-drug interactions are particularly relevant for
      drugs used to treat neurological and psychological diseases. This review provides
      an overview of food-drug interaction in the treatment of neurological and
      psychological diseases. A literature search was carried out by collecting data
      from different reviews, reports, and original articles on general or specific
      drug interactions with food, in patients with a variety of neurological and
      psychological diseases. Based on our review, we found that food-drug interactions
      may alter the expected impact of drug, or cause the development of a drug
      toxicity. Nutritional status of the patients may also be affected, particularly a
      change in body weight caused by a change appetite. Metabolism, absorption, and
      excretion of foods may also be altered, and nutritional insufficiencies may
      occur. Recent studies show that diet can have a strong influence on gut
      microbiota and thus, alter drug pharmacokinetics. Therefore, microbiota
      alterations should also be considered while assessing food-drug interactions.
      Knowledge of food-drug interactions is critical for improving health of patients
      with neurological and psychological diseases, and also for improving
      effectiveness of treatments.

PMID- 30295674
TI  - Rhizosphere microbiome structure alters to enable wilt resistance in tomato.
AB  - Tomato variety Hawaii 7996 is resistant to the soil-borne pathogen Ralstonia
      solanacearum, whereas the Moneymaker variety is susceptible to the pathogen. To
      evaluate whether plant-associated microorganisms have a role in disease
      resistance, we analyzed the rhizosphere microbiomes of both varieties in a
      mesocosm experiment. Microbiome structures differed between the two cultivars.
      Transplantation of rhizosphere microbiota from resistant plants suppressed
      disease symptoms in susceptible plants. Comparative analyses of rhizosphere
      metagenomes from resistant and susceptible plants enabled the identification and
      assembly of a flavobacterial genome that was far more abundant in the resistant
      plant rhizosphere microbiome than in that of the susceptible plant. We cultivated
      this flavobacterium, named TRM1, and found that it could suppress R. solanacearum
      disease development in a susceptible plant in pot experiments. Our findings
      reveal a role for native microbiota in protecting plants from microbial
      pathogens, and our approach charts a path toward the development of probiotics to
      ameliorate plant diseases.

PMID- 30295677
TI  - Charcot-Marie-Tooth type 1A drug therapies: role of adenylyl cyclase activity and
      G-protein coupled receptors in disease pathomechanism.
AB  - Charcot-Marie-Tooth type 1A (CMT1A) is a dysmyelinating disease of the peripheral
      nervous system that results in a slow progressive weakening and wasting of the
      distal muscles of the upper and lower limbs. Despite extensive research and
      clinical trials there is still no treatment for CMT1A that results in complete
      neurological improvement. Recent studies investigating various pharmacological
      modulators of adenylyl cyclase activity, including ascorbic acid and ligands of G
      protein-coupled receptors (GPCRs), provide hope for future treatments of this
      type of hereditary motor and sensory neuropathy. A review of mechanisms of action
      of several compounds tested for CMT1A in pre-clinical and clinical studies
      ascorbic acid, onapristone, PXT3003 (baclofen, naltrexone, and sorbitol), and
      ADX71441, very clearly indicates an important role for adenylyl cyclase activity
      and GPCRs in the pathomechanism of the disease. Metabotropic gamma-aminobutyric
      acid receptors (GABABR), subtype mu (MU) opioid receptors (MOR), and muscarinic
      acetylcholine receptors (mACh) appear to be particularly significant in both
      pathogenesis and treatment, and their activation may exert a similar and
      synergistic effect on the physiology of Schwann cells as well as neurons. These
      receptors participate in proliferation and differentiation of Schwann cells and
      influence excitatory transmission in neurons. We also hypothesize that
      onapristone might act through a non-classical mechanism via membrane progesterone
      receptor (mPR) and cAMP signaling. This review endeavors to outline a pathway
      leading inversely from therapy to an indispensable role for adenylyl cyclase
      activity and GPCRs in the modulation of dosage sensitive peripheral myelin
      protein (PMP22) gene expression.

PMID- 30295678
TI  - The role of DSCAM in the regulation of synaptic plasticity: possible involvement
      in neuropsychiatric disorders.
AB  - Synaptic plasticity simply put, is the activity-dependent modification of the
      strength or efficacy of synaptic transmission in the network of synapses in the
      brain. The role of synaptic plasticity in disease is an active area of research.
      Changes in plasticity translate to the release of neurotransmitters at the
      synapse and subsequently, the way humans see the world. It is known that
      neuropsychiatric disorders such as depression, posttraumatic stress disorder
      (PTSD), and Alzheimer's disease (AD) are related to pathological changes in
      dynamic processes in synapses, dialogue between neurons, and finally, changes in
      overall plasticity. To find a cure for these plasticity related diseases, it is
      imperative that we understand the precise mechanisms that perturb the homeostatic
      balance leading to the disease state. The aim of this review is to present what
      is currently known about DSCAM (Down Syndrome Cell Adhesion Molecule) a protein
      that is directly connected to pathological changes in synaptic plasticity. The
      review will present information on DSCAM and how it is connected to glutamate
      (Glu) and gamma-Aminobutyric acid (GABA) neurotransmission pathways. Finally, the
      review throws some light on the possible involvement of DSCAM in a spectrum of
      psychiatric disorders apart from Down syndrome (DS).

PMID- 30295679
TI  - Hindlimb suspension-induced cell apoptosis in the posterior parietal cortex and
      lateral geniculate nucleus: corresponding changes in c-Fos protein and the
      PI3K/Akt signaling pathway.
AB  - Recent physiological studies indicate that weightlessness reliably alters ocular
      structure and function, as well as the ability to process visual-spatial
      information. The posterior parietal cortex (PPC) and lateral geniculate nucleus
      (LGN) are two key brain areas implicated in the processing of visual-spatial
      information. Here, we used the modified tail-suspension rat model to simulate the
      physiological effects of microgravity. Rats were divided into four groups, which
      exposed to the simulated microgravity environment for 0 (Control group), 7, 14,
      or 28 days. We found a significant increase in cellular apoptosis in the PPC and
      the LGN after 7 days of simulated microgravity. In addition, there was an
      increase in expression of c-Fos protein in the PPC, and a repression of the
      PI3K/Akt signaling pathway in the LGN after 7 days. Based on these results, we
      conclude that short-term simulated microgravity may induce cell apoptosis in the
      PPC and LGN, and reflect a neural adaptive process to accommodate a microgravity
      environment.

PMID- 30295680
TI  - Effects of PINK1 mutation on synapses and behavior in the brain of Drosophila
      melanogaster.
AB  - Mutations in the PINK1 gene are responsible for typical symptoms of Parkinson's
      disease. Using Drosophila melanogaster mutant PINK1B9 and after PINK1 silencing
      with RNAi using transgenic lines, we observed defects in synapses and behavior.
      The lack or reduced expression of PINK1 prolonged sleep during the day (nap) and
      decreased the total locomotor activity during 24 h, in addition to a decrease in
      climbing ability and a reduced lifespan. In the brain, PINK1 mutants had a lower
      level of Bruchpilot (BRP), a presynaptic scaffolding protein that is crucial for
      neurotransmission in all type of synapses in Drosophila. In addition, other
      proteins that are involved in synaptic transmission; Rab5, Syntaxin and Wishful
      Thinking were also decreased in abundance in mutants, except Synaptotagmin.
      Transmission electron microscopy (TEM) also confirmed less and abnormal synaptic
      vesicles at tetrad synapses in the visual system of PINK1 mutants. The lower
      level of BRP and longer day sleep observed was also detected in white mutants,
      which were examined to test the effect of the?r?nwhite background on the PINK1B9
      strain. The reduced locomotor activity and longer day sleep in PINK1 mutants and
      after decreasing the PINK1 level in neurons seem to be correlated with a decrease
      in mitochondria number during the day, when they normally peak, and with impaired
      synaptic transmission.

PMID- 30295681
TI  - Effects of extensive amygdaloid lesions on conditioned taste aversion in rats.
AB  - The role of the amygdala in the acquisition of conditioned taste aversion (CTA)
      is unclear. The lesion studies that have explored specific nuclei of the amygdala
      point to a probable involvement of the basolateral amygdala, but it remains
      unclear whether the function of the amygdala in CTA is limited to the activity of
      the basolateral amygdala. In the current study, extensive bilateral lesions of
      the amygdala were performed in Wistar rats to explore if the destruction of the
      amygdala affects the acquisition of CTA, as has been reported with selective
      lesions of the basolateral amygdala. The magnitude of the taste aversion of
      animals with extensive lesions of the amygdala was compared with those of animals
      with similar lesions of the striatum (a structure apparently unrelated to CTA)
      and animals without lesions. Taste aversion was analyzed by the one-bottle test
      and two-bottle choice test. The results of the one-bottle test indicated that
      amygdaloid lesions significantly reduced the magnitude of taste aversion compared
      with that of animals without lesions. Animals with lesions of the amygdala also
      showed a greater preference for the conditioned taste stimulus, but this
      preference did not reach statistical significance. Besides the effect on CTA,
      animals with amygdaloid lesions showed no evidence of taste neophobia on the day
      of conditioning. These findings suggest that amygdaloid lesions may affect CTA by
      disrupting the perception of novelty during conditioning in a manner similar to
      the effect reported with basolateral lesions.

PMID- 30295683
TI  - Testosterone enhancement during pregnancy influences social coping and gene
      expression of oxytocin and vasopressin in the brain of adult rats.
AB  - Steroid hormones are important mediators of prenatal maternal effects and play an
      important role in fetal programming. The aim of our study was to investigate how
      testosterone enhancement during pregnancy influences neurobehavioral aspects of
      social coping of rat offspring in adulthood. Pregnant rat dams were exposed to
      depot form of testosterone during the last third of pregnancy (i.e., beginning on
      the 14th day of pregnancy). Their adult offspring were later tested in a social
      interaction test and expression of oxytocin and arginine-vasopressin mRNA in the
      hypothalamic nuclei was evaluated. Our research showed that prenatal exposure to
      higher levels of testosterone activated socio-cohesive and socio-aversive
      interactions, but only in males. The testosterone-exposed group also showed
      decreased oxytocin mRNA expression in the supraoptic and paraventricular nuclei
      of the hypothalamus, and increased arginine-vasopressin mRNA expression in the
      supraoptic and suprachiasmatic nuclei as compared to controls. However, we did
      not observe any sex differences in the expression of oxytocin and arginine
      vasopressin mRNA in these regions. Our findings show that testosterone
      enhancement in pregnancy could have long-lasting effects on oxytocin and arginine
      vasopressin levels in the brain of adult animals, but lead to changes in
      behavioral aspects of coping strategies only in males.

PMID- 30295682
TI  - Afferent projections of the subthalamic nucleus in the rat: emphasis on bilateral
      and interhemispheric connections.
AB  - The subthalamic nucleus (STN) is important for normal movement as well as in
      movement disorders. The STN is a target nuclei in patients with advanced
      Parkinson's disease (PD). Deep brain stimulation (DBS) is a standard surgical
      treatment for PD. Although DBS results in a significant reduction in motor
      disability, several negative side effects have been reported. Thus, to understand
      the side effects of DBS the connection of the STN should be well known.
      Therefore, the present study aims to re-examine the STN with an emphasis on
      poorly- or un-documented connections. Furthermore, the bilateral and
      interhemispheric connections of the STN are evaluated. Fifteen male albino rats
      received injections of Fluoro-Gold retrograde and biotinylated dextran amine
      anterograde tracers into the STN. Following a 7-10 day survival period, the
      animals were processed according to the relevant protocol for each tracer. The
      present study demonstrates ipsilateral connections of the STN with cortical
      regions (i.e., infralimbic, cingulate, frontal, piriform, primary motor, primary
      sensory, insular and retrosplenial cortices), the endopiriform nucleus, basal
      ganglia related structures (i.e., caudate putamen, globus pallidus, ventral
      pallidum, nucleus accumbens, claustrum and substantia innominata) and the deep
      cerebellar nuclei (i.e., lateral, anterior interposed). Bilateral connections of
      the STN were observed with limbic (amygdala, bed nucleus of stria terminalis),
      hypothalamic (ventromedial, posterior, anterior, lateral and mammillary) thalamic
      (thalamic reticular nucleus), epithalamic (habenular nucleus), and brainstem
      structures (superior colliculus, substantia nigra, spinal nucleus of the
      trigeminal nerve, red nucleus, dorsal raphe nucleus, pedunculopontine tegmental
      nuclei). Interhemispheric connections between left and right STN were also
      observed. The present study fills important gaps in connectivity of the STN. In
      particular, we report STN connectivity with cortical areas (i.e., piriform,
      endopiriform and insular), claustrum, hypothalamic, thalamic reticular,
      cerebellar, habenular, trigeminal, red, cuneate and gracile nuclei and substantia
      innominate. These connections, which have not been previously described or poorly
      described, provide new routes that can alter the conceptual architecture of the
      basal ganglia circuitry and may modify our view of the functional identity of the
      STN.

PMID- 30295684
TI  - The use of MR-less MNI based neuronavigation for 10 Hz rTMS depression therapy:
      electrophysiological and clinical implications.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is a popular and effective
      treatment for drug resistant depression. However, there is considerable
      variability in clinical outcomes, in previous studies and between patients.
      Because of high requirements for the use of fMRI based neuronavigation, many
      practitioners of rTMS still choose to use a standard 5 cm rule for rTMS coil
      placement which leads to large variations in which brain regions are being
      stimulated. We decided to test the possibilities of a MNI based MR-less
      neuronavigation system in rTMS depression treatment, by comparing the
      physiological effects and clinical outcomes of 3 distinct stimulation targets.
      Forty-six patients (thirty-three female, thirteen male) from the Republican
      Vilnius psychiatric hospital, all with drug resistant depressive disorder,
      participated in the study. All patients received high frequency (10 Hz)
      stimulation for 10 to 15 daily rTMS sessions. However, before the treatment they
      were randomly sorted into 3 groups according to stimulation target in MNI map:
      Group 1 received rTMS at point -40; 48; 35; Group 2 received rTMS at point -46;
      45; 38; Group 3 received rTMS at point -38; 44; 26. Electroencephalography (EEG)
      recordings and clinical tests were obtained the day before the rTMS course and
      after the last session. There were some notable differences in physiological
      changes between the groups, with the largest EEG band spectral power increases
      found in Group 1 patients and the lowest in Group 2 patients. There was a
      significantly larger decrease of the Hamilton Depression Rating Scale (HAM-D)
      scores in the Group 3 (66.94%) compared to Group 1 (57.52%) and Group 2 (56.02%).
      This suggests it is possible to achieve higher clinical efficacy and less
      physiological impact on the brain when using different targets in a
      neuronavigated MNI based MR-less rTMS system.

PMID- 30295685
TI  - MMP-3 deficiency does not influence the length and number of CA1 dendrites of
      hippocampus of adult mice.
AB  - Over the past two decades, metalloproteinases (MMPs), including MMP-2, MMP-3, and
      MMP-9, have been implicated as important players in mechanisms underlying various
      forms of neuroplasticity. In particular, MMP-3 was found to be involved in both
      cognitive functions and in plasticity phenomena, but the underlying molecular
      mechanisms remain largely elusive. In general, it is believed that functional
      plasticity of neurons is associated with morphological alterations.
      Interestingly, MMP-9, in addition to playing a key role in synaptic plasticity,
      was found to affect plasticity-related spine morphology changes. Whereas the
      involvement of MMP-3 in shaping synapse morphology upon induction of synaptic
      plasticity awaits determination, it has been demostrated that MMP-3 knockout
      results in clearly altered apical dendrite morphology in pyramidal neurons in
      mouse visual cortex. Considering that the involvement of MMP-3 in synaptic
      plasticity has been most extensively documented for the CA1 hippocampal region,
      we decided to investigate whether genetic deletion of MMP-3 affects neuronal
      morphology in this area. To this end, we used Golgi staining to compare dendritic
      morphology of pyramidal neurons in the CA1 region in MMP-3-deficient and wild
      type mice. Surprisingly, in contrast to the results obtained in cortex, extensive
      analysis of dendritic morphology in the CA1 region revealed no significant
      differences between MMP-3 knockout and wild-type groups. These results suggest
      that the impact of MMP-3 on neuronal morphology may be region-specific.

PMID- 30295686
TI  - Polycomb repressive complex 2 binds RNA irrespective of stereochemistry.
AB  - The Polycomb Repressive Complex 2 (PRC2) interacts promiscuously with G
      quadruplex (G4) RNA structures. Herein, we tested the limit of this promiscuity
      by exploring the interaction of PRC2 with G4 RNAs comprised of l-ribonucleic
      acids (l-RNA), the enantiomer of naturally occurring d-RNA. Remarkably, we find
      that PRC2 binds similarly to both d- and l-G4 RNAs, suggesting that these
      interactions are independent of stereochemistry. Moreover, we show that d- and l
      RNAs bind to the same site on PRC2, enabling l-G4 RNAs to outcompete native
      substrates for binding. This work challenges the prevailing assumption that l
      oligonucleotides are "invisible" to native biology and provides a unique
      opportunity to develop a novel class of PRC2 inhibitors based on nuclease
      resistant l-RNA.

PMID- 30295687
TI  - Rational design of time-resolved turn-on fluorescence sensors: exploiting delayed
      fluorescence for hydrogen peroxide sensing.
AB  - Weakly emissive phosphine compounds, which contain a carbazolyl donor
      triarylboryl acceptor luminophore, become strongly delayed fluorescent upon
      changes to their oxide forms. Time-gated acquisition of the fluorescence signals
      of phosphine in the presence of H2O2 and a competitive fluorescence dye allow for
      detection of H2O2 with elimination of short-lived fluorescence noise.

PMID- 30295688
TI  - Salt-mediated synthesis of bimetallic networks with structural defects and their
      enhanced catalytic performances.
AB  - A method to synthesize bimetallic alloys with tunable morphologies and controlled
      structural defects was proposed using the characteristics of emulsions tailored
      by salts. AuPd and PtPd nanowire networks with abundant structural defects
      exhibited outstanding catalytic performances for oxidation of 5
      hydroxymethylfurfural to 2,5-furandicarboxylic acid, because of the strong
      ability to generate radicals.

PMID- 30295689
TI  - A dual chemosensor for Cu2+ and Hg2+ based on a rhodamine-terminated water
      soluble polymer in 100% aqueous solution.
AB  - A novel water-soluble polymer bearing a rhodamine receptor (PEGSRh) was
      synthesized as a dual chemosensor for the recognition of Cu2+ and Hg2+ in 100%
      aqueous solution. PEGSRh not only exhibited a sensitive colorimetric response
      towards Cu2+ and Hg2+ but also showed a selective turn-on fluorescence response
      towards Hg2+ over other metal ions. The binding stoichiometry for the
      complexation of PEGSRh with Cu2+ and Hg2+ was confirmed to be 1 : 1 by Job plot
      analysis. The low detection limits were found to be 5.92 * 10-7 M for Cu2+ and
      2.85 * 10-6 M for Hg2+. The responses of PEGSRh to Cu2+ and Hg2+ were both stable
      over wide pH ranges. In addition, the fluorescence intensity changes of PEGSRh
      solution by the inputs of Hg2+, Cu2+ and EDTA have been used to construct a
      combinational logic gate. Again, an INHIBIT logic gate was also obtained by
      employing Cu2+ and EDTA as the chemical inputs and the absorbance signal as the
      output. Moreover, test papers were prepared facilely using PEGSRh for practical
      on-site detection of Cu2+ and Hg2+.

PMID- 30295690
TI  - Plutonium chlorido nitrato complexes: ligand competition and computational
      metrics for assembly and bonding.
AB  - Four new [Pu(iv)Cln(NO3)6-n]2- (n = 0, 2, 3) and [Pu(vi)O2Cl3(NO3)]2- containing
      materials were crystallized from acidic, aqueous media and structurally
      characterized. The anions are assembled via hydrogen and halogen bonding motifs,
      which are rationalized computationally. The Pu-NO3 and -Cl bonds were probed
      using QTAIM and NLMO analyses and found to be polar and largely ionic.

PMID- 30295692
TI  - Ordered nanoporous lyotropic liquid crystal polymer resin for heterogeneous
      catalytic aerobic oxidation of alcohols.
AB  - An ordered, nanoporous, TEMPO-based polymer resin formed from lyotropic liquid
      crystal monomers catalyzes the hetereogeneous oxidation of alcohols with high
      activity and substrate size selectivity under transition-metal-free, aerobic
      conditions.

PMID- 30295693
TI  - Patent foramen ovale causing breathlessness and platypnoea-orthodeoxia syndrome
      in an older patient.
AB  - An 82-year-old male presented with a week's history of shortness of breath on
      exertion, particularly when bending to tie his shoe laces. The breathlessness
      worsened on standing and was relieved by lying. His oxygen saturations were noted
      to fluctuate based on position dropping to 82% on standing. This was suggestive
      of platypnoea-orthodeoxia syndrome (POS), an uncommon but potentially reversible
      diagnosis. As the population ages we may be more likely to see patients with
      persisting patent foramen ovale decompensate and develop POS.

PMID- 30295691
TI  - Direct monitoring of the conformational equilibria of the activation loop in the
      mitogen-activated protein kinase p38alpha.
AB  - Conformational transitions in protein kinases are crucial for the biological
      function of these enzymes. Here, we characterize and assess conformational
      equilibria of the activation loop and the effect of small molecule inhibitors in
      the MAP kinase p38alpha. Our work experimentally revealed the existence of a two
      state equilibrium for p38alpha while the addition of inhibitors shifts the
      equilibrium between these two states.

PMID- 30295694
TI  - Effects of Cannabis Use and Subclinical ADHD Symptomology on Attention Based
      Tasks in Adolescents and Young Adults.
AB  - Objective: Research has demonstrated comorbidity between Attention-Deficit
      Hyperactivity Disorder (ADHD) and cannabis use, and some have proposed that
      subclinical ADHD symptoms may explain attentional deficits in cannabis users.
      Here we investigated whether subclinical ADHD symptoms and cannabis use
      independently or interactively predict performance on attention tasks in
      adolescents and young adults. Method: Seventy-two participants (cannabis users
      (MJ) = 34, Controls = 38) completed neuropsychological tasks of inhibition and
      attention. Parent report on the Child Behaviors Checklist reflected current ADHD
      symptoms. Multiple regression analyses examined whether ADHD symptoms and
      cannabis use independently or interactively predicted cognitive outcomes.
      Results: Cannabis use was significantly associated with slower CPT hit rate
      response. Subclinical ADHD symptoms did not independently predict or moderate
      cannabis effects. Conclusions: Cannabis users demonstrated slower response rate
      during an attentional task. Subclinical ADHD symptoms did not predict any
      deficits. As such, attention deficits seen in cannabis users are more related to
      substance use than ADHD symptomatology.

PMID- 30295696
TI  - Contributing Towards a Cultural Neuropsychology Assessment Decision-Making
      Framework: Comparison of WAIS-IV Norms from Colombia, Chile, Mexico, Spain,
      United States, and Canada.
AB  - Objective: Test and normative data selection in cross-cultural neuropsychology
      remain a complex issue. Despite growing awareness, more studies and instruments
      are needed to adequately address the impact of cultural factors, such as quantity
      and quality of education. In this study, we examine the interpretive effects of
      applying six relevant WAIS-IV norms to a Colombian sample. Method: A sample of
      305 highly educated Colombian corporate executives completed the WAIS-IV. Data
      were scored using norms from Colombia, Chile, Mexico, Spain, United States, and
      Canada and scores were compared using ANOVA. Additionally, a comparative
      sociodemographic framework was established to contextualize our sample to the
      standardization samples and populations of the six countries. Results: Colombian
      and Chilean norms yielded systematically similar FSIQ/Index scores (mean range =
      117-121), while incrementally lower scores were found with norms from Mexico (-3
      9 points), Spain (-3-11 points), USA (-8-13 points), and Canada (-11-18 points).
      Verbal scores differed, with highest scores obtained with Mexican and Spanish
      norms. Working memory and processing speed scores had the lowest score agreement
      across norms. Conclusions: Although the Chilean norms are more frequently used in
      Colombia, the recently developed Colombian norms appear optimal for our sample;
      the scores do not have meaningful differences with those obtained with Chilean
      norms and offer local population representation fidelity. Mexican, Spanish, US,
      and Canadian norms underestimated WAIS-IV scores and distorted the sample's score
      distribution. Finally, verbal scores highlight potential education representation
      within Spanish and Mexican norms, while working memory and processing speed
      scores suggest cultural nuances likely captured within different norms.

PMID- 30295695
TI  - Starting the Fight in the Tumor: Expert Recommendations for the Development of
      Human Intratumoral Immunotherapy (HIT-IT).
AB  - A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held
      in Paris on 08 March 2018 which comprised 11 experts from academia, 11 experts
      from the pharmaceutical industry and two clinicians who were representatives of
      ESMO. The focus of the meeting was exclusively on the intratumoral
      injection/delivery of immunostimulatory agents with the aim of harmonizing the
      standard terms and methodologies used in the reporting of human intratumoral
      immunotherapy (HIT-IT) clinical trials to ensure quality assurance and avoid a
      blurring of the data reported from different studies. The goal was to provide a
      reference document, endorsed by the panel members, that could provide guidance to
      clinical investigators, pharmaceutical companies, ethics committees, independent
      review boards, patient advocates and the regulatory authorities, and promote an
      increase in the number and quality of HIT-IT clinical trials in the future.
      Particular emphasis was placed not only on the development of precise definitions
      to facilitate a better understanding between investigators, but also on the
      importance of systematic serial biopsies as a driver for translational research
      and the need for the recording and reporting of data, to facilitate a better
      understanding of the key processes involved.

PMID- 30295697
TI  - Strain-GeMS: Optimized subspecies identification from microbiome data based on
      accurate variant modeling.
AB  - Motivation: Subspecies identification is one of the most critical issues in
      microbiome studies, as it is directly related to their functions in response to
      the environmental stress and their feedbacks. However, identification of
      subspecies remains a challenge largely due to the small variation between
      different strains within the same species. Accurate identification of subspecies
      primarily relies on variant identification and categorization through microbiome
      data. However current SNP calling and subspecies identification for microbiome
      data remain underdeveloped. Results: In this work, we have proposed Strain-GeMS
      for subspecies identification from microbiome data, based on solid statistical
      model for SNP calling, as well as optimized procedure for subspecies
      identification. Results on simulated, ab initio and in vivo datasets have shown
      that Strain-GeMS could always generate more accurate results compared with other
      subspecies identification methods. Availability and implementation: Strain-GeMS
      is available at: https://github.com/HUST-NingKang-Lab/straingems. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 30295698
TI  - Inferring disease-associated long non-coding RNAs using genome-wide tissue
      expression profiles.
AB  - Motivation: Long non-coding RNAs (lncRNAs) are important regulators in wide
      variety of biological processes, which are linked to many diseases. Compared to
      protein-coding genes (PCGs), the association between diseases and lncRNAs is
      still not well studied. Thus, inferring disease-associated lncRNAs on a genome
      wide scale has become imperative. Results: In this study, we propose a machine
      learning-based method, DislncRF, which infers disease-associated lncRNAs on a
      genome-wide scale based on tissue expression profiles. DislncRF uses random
      forest models trained on expression profiles of known disease-associated PCGs
      across human tissues to extract general patterns between expression profiles and
      diseases. These models are then applied to score associations between lncRNAs and
      diseases. DislncRF was benchmarked against a gold standard data set and compared
      to other methods. The results show that DislncRF yields promising performance and
      outperforms the existing methods. The utility of DislncRF is further
      substantiated on two diseases in which we find that top scoring candidates are
      supported by literature or independent data sets. Availability:
      https://github.com/xypan1232/DislncRF. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 30295699
TI  - sRNAPrimerDB: Comprehensive primer design and search web service for small non
      coding RNAs.
AB  - Motivation: Small non-coding RNAs (ncRNAs), especially microRNAs (miRNAs) and
      piwi-interacting RNAs (piRNAs), play key roles in many biological processes.
      However, only a few tools can be used to develop the optimal primer or probe
      design for the expression profile of small ncRNAs. Here, we developed
      sRNAPrimerDB, the first automated primer designing and query web service for
      small ncRNAs. Results: The primer online designing module of sRNAPrimerDB is
      composed of primer design algorithms and quality evaluation of the polymerase
      chain reaction (PCR) primer. Five types of primers, namely, generic or specific
      reverse transcription primers, specific PCR primers pairs, TaqMan probe, double
      hairpin probe, and hybridization probe for different small ncRNA detection
      methods, can be designed and searched using this service. The quality of PCR
      primers is further evaluated using melting temperature, primer dimer, hairpin
      structure, and specificity. Moreover, the sequence and size of each amplicon are
      also provided for the subsequent experiment verification. At present, 531,306 and
      2,941,669 primer pairs exist across 223 species for miRNAs and piRNAs,
      respectively, according to sRNAPrimerDB. Several primers designed by sRNAPrimerDB
      are further successfully validated by subsequent experiments. Availability:
      sRNAPrimerDB is a valuable platform that can be used to detect small ncRNAs. This
      module can be publicly accessible at http://www.srnaprimerdb.com or
      http://123.57.239.141. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 30295701
TI  - Multi-insight visualization of multi-omics data via ensemble dimension reduction
      and tensor factorization.
AB  - Motivation: Visualization of high-dimensional data is an important step in
      exploratory data analysis and knowledge discovery. However, it is challenging,
      because the interpretation is highly subjective. If we see dimensionality
      reduction (DR) techniques as the main tool for data visualization, they are like
      multiple cameras that look into the data from different perspectives or angles.
      We can hardly prescribe one single perspective for all datasets and problems. One
      snapshot of data cannot reveal all the relevant aspects of the data in higher
      dimensions. The reason is that each of these methods has its own specific
      strategy, normally based on well-established mathematical theories to obtain a
      low-dimensional projection of the data, which sometimes is totally different from
      the others. Therefore, relying only on one single projection can be risky,
      because it can close our eyes to important parts of the full knowledge space.
      Results: We propose the first framework for multi-insight data visualization of
      multi-omics data. This approach, contrary to single-insight approaches, is able
      to uncover the majority of data features through multiple insights. The main idea
      behind the methodology is to combine several DR methods via tensor factorization
      and group the solutions into an optimal number of clusters (or insights). The
      experimental evaluation with low-dimensional synthetic data, simulated multi
      omics data related to ovarian cancer, as well as real multi-omics data related to
      breast cancer show the competitive advantage over state-of-the-art methods.
      Supplementary information: Supplementary data are available at Bioinformatics
      online. Availability and implementationhttps://folk.uio.no/hadift/MIV/ [user/pass
      via hadift@medisin.uio.no].

PMID- 30295702
TI  - Metwork: a web server for natural products anticipation.
AB  - Motivation: The annotation of natural products and more generally small molecules
      is one of the major drawbacks in untargeted mass spectrometry analysis. Molecular
      networking has emerged as a structured way to organize and mine data from
      untargeted tandem mass spectrometry (MS/MS) experiments. Despite the great
      potential of this tool, the annotation is usually performed manually by the
      expert as only few spectral libraries are available. Results: Herein we propose a
      web server of in silico metabolization of metabolites that represents a full
      implementation of the metabolome consistency concept. The workflow is based on
      MS/MS data, organized in molecular network using the Global Natural Products
      Social Molecular Networking (GNPS) platform, a collaborative library of reactions
      and a MS/MS spectra prediction module. Having one node identified in the
      molecular network, the server generates putative structures and predict the
      associated MS/MS spectra when the exact mass is detected in the network. A
      similarity comparison between the MS/MS spectra is then performed in order to
      annotate the node. Availability: The web server is available at:
      https://metwork.pharmacie.parisdescartes.fr.

PMID- 30295700
TI  - Type of infant formula increases early weight gain and impacts energy balance: a
      randomized controlled trial.
AB  - Background: Millions of infants are fed breast milk substitutes, and the type of
      infant formula can impact weight gain patterns. Objective: We conducted a
      randomized controlled trial to determine the direct impact of 2 types of infant
      formula (cow milk formula, CMF; extensively protein hydrolyzed formula, EHF) on
      growth and energy balance. Design: A racially diverse group of formula-fed
      infants (n = 113) were randomly assigned to either CMF or EHF from the age of
      0.75 to 12.5 mo. At each monthly visit, anthropometric measures were obtained to
      determine growth z scores and weight gain velocity, and to categorize early
      weight gain patterns as rapid or nonrapid. Also, diet records were collected to
      determine energy from formula and other sources. Comprehensive assessments of
      energy balance (intake, expenditure, loss) were made at 0.75, 3.5, and 12.5 mo.
      Results: Beginning 3 wk after randomization, CMF infants had significantly higher
      weight, but not length, z scores than did EHF infants, and this persisted after
      solid foods complemented the formula diet. On average, weight gain velocity from
      0.75 to 4.5 mo was within the range of typically growing infants for both groups,
      yet velocity was 3.9 g/d greater for CMF infants (P = 0.002), who were more
      likely to be classified as an early rapid weight gainer, than EHF infants (46%
      compared with 18%; P = 0.007). Early differences in energy intake and fecal loss,
      yielding greater energy available for deposition among CMF infants, contributed
      to the differential weight gain patterns. There were no significant differences
      between the formula treatment groups in total energy expenditure or sleeping
      energy expenditure. Conclusions: Among healthy infants, the type of formula
      impacted on early rapid weight gain patterns owing to energy intake and loss
      mechanisms. Research is needed to identify the macronutrients and other
      compositional constituents in EHF and breast milk that promote satiation and
      healthy weight gain during sensitive periods of development. This trial was
      registered at clinicaltrials.gov as: NCT01700205.

PMID- 30295703
TI  - DeepHINT: Understanding HIV-1 integration via deep learning with attention.
AB  - Motivation: Human immunodeficiency virus type 1 (HIV-1) genome integration is
      closely related to clinical latency and viral rebound. In addition to human DNA
      sequences that directly interact with the integration machinery, the selection of
      HIV integration sites has also been shown to depend on the heterogeneous genomic
      context around a large region, which greatly hinders the prediction and
      mechanistic studies of HIV integration. Results: We have developed an attention
      based deep learning framework, named DeepHINT, to simultaneously provide accurate
      prediction of HIV integration sites and mechanistic explanations of the detected
      sites. Extensive tests on a high-density HIV integration site dataset showed that
      DeepHINT can outperform conventional modeling strategies by automatically
      learning the genomic context of HIV integration from primary DNA sequence alone
      or together with epigenetic information. Systematic analyses on diverse known
      factors of HIV integration further validated the biological relevance of the
      prediction results. More importantly, in-depth analyses of the attention values
      output by DeepHINT revealed intriguing mechanistic implications in the selection
      of HIV integration sites, including potential roles of several DNA-binding
      proteins. These results established DeepHINT as an effective and explainable deep
      learning framework for the prediction and mechanistic study of HIV integration.
      Availability: DeepHINT is available as an open-source software and can be
      downloaded from https://github.com/nonnerdling/DeepHINT. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 30295704
TI  - Bayesian negative binomial regression for differential expression with
      confounding factors.

PMID- 30295705
TI  - Hereditary haemorrhagic telangiectasia with multiple complications presenting in
      an older patient.
AB  - Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant multi
      organ vascular disorder associated with bleeding and a reduced life expectancy.
      We present a 91-year-old woman with complications of previously undiagnosed HHT.
      This case demonstrates three potential complications: pulmonary arteriovenous
      malformation (AVM) resulting in a right to left shunt, cerebral infarctions and
      pericardial effusion. Despite these potentially life-threatening complications
      and the reduced life-expectancy associated with HHT the patient has survived to
      an advanced age. Due to the patient's late diagnosis and frailty, the treatment
      options of AVM embolization and pericardiocentesis were deemed inappropriate. The
      patient was treated with tranexamic acid to reduce bleeding severity and
      discharged home with a care package and home oxygen.

PMID- 30295706
TI  - Optimal Use Ratio of the Stromal Vascular Fraction (SVF): An Animal Experiment
      Based on Micro-CT Dynamic Detection After Large-Volume Fat Grafting.
AB  - Background: The addition of the stromal vascular fraction (SVF) can enhance the
      postoperative survival rate of fat. However, a universal SVF application method
      is currently unavailable. Therefore, a simple and convenient guideline for SVF
      addition is needed for its clinical application. Objectives: To evaluate whether
      SVF can improve fat survival after large-volume fat grafting, and to find a
      simple and convenient standard for the clinical use of SVF. Methods: Patient fat
      samples were obtained after liposuction for SVF preparation and grafting. Four
      types of grafts were prepared with different SVF ratios: 0:1, 1:1, 2:1 and 4:1
      SVF:fat. After intensive mixing, fat grafts (5 ml) were randomly injected into
      both sides of the backs of athymic rats (n=15). At 24 hours and 1, 3, 6, and 9
      months after the operation, microcomputed tomography (micro-CT) scanning was
      performed to calculate the fat survival rate. Results: Nine months after the
      operation, the survival rates of fat in the four groups were 8.89 +/- 1.62%
      (0:1), 18.26 +/- 3.85% (1:1), 8.83 +/- 1.46% (2:1), and 7.96 +/- 1.31% (4:1). The
      1:1 group exhibited the greatest survival rate (P <0.01), and the adipose tissue
      histological patterns and blood vessel quality were enhanced compared with those
      in the other groups. Conclusions: An appropriate SVF ratio can increase the fat
      survival rate after large-volume fat grafting, but no linear relationship exists
      between the SVF ratio and fat survival. The optimal SVF:fat ratio for grafting is
      1:1.

PMID- 30295707
TI  - Tenascin-C Accelerates Adverse Ventricular Remodeling after Myocardial Infarction
      by Modulating Macrophage Polarization.
AB  - Aims: Tenascin-C (TN-C) is an extracellular matrix protein undetected in the
      normal adult heart, but expressed in several heart diseases associated with
      inflammation. We previously reported that serum TN-C levels of myocardial
      infarction (MI) patients were elevated during the acute stage, and that patients
      with high peak TN-C levels were at high risk of left ventricular (LV) remodeling
      and poor outcome, suggesting that TN-C could play a significant role in the
      progression of ventricular remodeling. However, the detailed molecular mechanisms
      associated with this process remain unknown. We aimed to elucidate the role and
      underlying mechanisms associated with TN-C in adverse remodeling after MI.
      Methods and Results: MI was induced by permanent ligation of the coronary artery
      of TN-C knockout (TN-C-KO) and wild-type (WT) mice. In WT mice, TN-C was
      expressed at the borders between intact and necrotic areas, with a peak at 3-days
      post-MI and observed in the immediate vicinity of infiltrating macrophages. TN-C
      KO mice were protected from ventricular adverse remodeling as evidenced by a
      higher LV ejection fraction as compared with WT mice (19.0+/-6.3% vs. 10.6+/
      4.4%; P < 0.001) at 3 months post-MI. During the acute phase, flow-cytometric
      analyses showed a decrease in F4/80+CD206lowCD45+ M1 macrophages and an increase
      in F4/80+CD206highCD45+ M2 macrophages in the TN-C-KO heart. To clarify the role
      of TN-C on macrophage polarization, we examined the direct effect of TN-C on bone
      marrow-derived macrophages in culture, observing that TN-C promoted macrophage
      shifting into an M1 phenotype via Toll-like receptor 4 (TLR4). Under M2-skewing
      conditions, TN-C suppressed the expression of interferon regulatory factor 4, a
      key transcription factor that controls M2-macrophage polarization, via TLR4,
      thereby inhibiting M2 polarization. Conclusions: These results suggested that TN
      C accelerates LV remodeling after MI, at least in part, by modulating M1/M2
      macrophage polarization.

PMID- 30295708
TI  - The genome of the oyster Saccostrea offers insight into the environmental
      resilience of bivalves.
AB  - Oysters are keystone species in estuarine ecosystems and are of substantial
      economic value to fisheries and aquaculture worldwide. Contending with disease
      and environmental stress are considerable challenges to oyster culture. Here we
      report a draft genome of the Sydney Rock Oyster, Saccostrea glomerata, an iconic
      and commercially important species of edible oyster in Australia known for its
      enhanced resilience to harsh environmental conditions. This is the second
      reference genome to be reported from the family Ostreidae enabling a genus-level
      study of lophotrochozoan genome evolution. Our analysis of the 784-megabase S.
      glomerata genome shows extensive expansions of gene families associated with
      immunological non-self-recognition. Transcriptomic analysis revealed highly
      tissue-specific patterns of expression among these genes, suggesting a complex
      assortment of immune receptors provide this oyster with a unique capacity to
      recognize invading microbes. Several gene families involved in stress response
      are notably expanded in Saccostrea compared with other oysters, and likely key to
      this species' adaptations for improved survival higher in the intertidal zone.
      The Sydney Rock Oyster genome provides a valuable resource for future research in
      molluscan biology, evolution and environmental resilience. Its close relatedness
      to Crassostrea will further comparative studies, advancing the means for improved
      oyster agriculture and conservation.

PMID- 30295709
TI  - Representing Multiple Observed Actions in the Motor System.
AB  - There is now converging evidence that others' actions are represented in the
      motor system. However, social cognition requires us to represent not only the
      actions but also the interactions of others. To do so, it is imperative that the
      motor system can represent multiple observed actions. The current fMRI study
      investigated whether this is possible by measuring brain activity from 29
      participants while they observed 2 right hands performing sign language gestures.
      Three key results were obtained. First, brain activity in the premotor and
      parietal motor cortex was stronger when 2 hands performed 2 different gestures
      than when 1 hand performed a single gesture. Second, both individual observed
      gestures could be decoded from brain activity in the same 2 regions. Third,
      observing 2 different gestures compared with 2 identical gestures activated brain
      areas related to motor conflict, and this activity was correlated with parietal
      motor activity. Together, these results show that the motor system is able to
      represent multiple observed actions, and as such reveal a potential mechanism by
      which third-party social encounters could be processed in the brain.

PMID- 30295710
TI  - Diadenosine-Polyphosphate Analogue AppCH2ppA Suppresses Seizures by Enhancing
      Adenosine Signaling in the Cortex.
AB  - Epilepsy is a multifactorial disorder associated with neuronal hyperexcitability
      that affects more than 1% of the human population. It has long been known that
      adenosine can reduce seizure generation in animal models of epilepsies. However,
      in addition to various side effects, the instability of adenosine has precluded
      its use as an anticonvulsant treatment. Here we report that a stable analogue of
      diadenosine-tetraphosphate: AppCH2ppA effectively suppresses spontaneous
      epileptiform activity in vitro and in vivo in a Tuberous Sclerosis Complex (TSC)
      mouse model (Tsc1+/-), and in postsurgery cortical samples from TSC human
      patients. These effects are mediated by enhanced adenosine signaling in the
      cortex post local neuronal adenosine release. The released adenosine induces A1
      receptor-dependent activation of potassium channels thereby reducing neuronal
      excitability, temporal summation, and hypersynchronicity. AppCH2ppA does not
      cause any disturbances of the main vital autonomous functions of Tsc1+/- mice in
      vivo. Therefore, we propose this compound to be a potent new candidate for
      adenosine-related treatment strategies to suppress intractable epilepsies.

PMID- 30295711
TI  - Massive expansion of bitter taste receptors in blind cavefish, Astyanax
      mexicanus.
AB  - A sensory deficit both at the individual and the species level can be compensated
      by increased acuity in other senses. The loss of vision in blind cavefish,
      Astyanaxmexicanus appears to be partially counterbalanced by enhanced
      chemosensory perception. Whether such improvement also involves adaptive changes
      in chemosensory receptor repertoires was unknown. The typical bitter taste
      receptor repertoire of teleost fishes is reported as three to five genes, much
      smaller than that of many terrestrial species. Interestingly, several fish
      species, e.g. mudskipper, have evolved a terrestric life style, but again it was
      unknown, whether this change in habitat is reflected in the size of gustatory
      receptor repertoires. We have searched the genomes of fifteen fish species and
      performed a thorough phylogenetic analysis to delineate their bitter taste
      receptor repertoires. We report no adaptation for four mudskipper species, which
      exhibit 3-4 bitter taste receptor genes, and thus a typical teleost repertoire,
      shaped by few gene losses and minor gene duplications from an ancestral
      repertoire of four genes. However, and in sharp contrast to all other teleost
      fish species analysed, blind cavefish possess over twenty intact bitter taste
      receptors plus several pseudogenes, rivalling the complexity of the human bitter
      taste receptor repertoire. The gene duplications giving rise to the current
      cavefish bitter taste receptor repertoire appear to have occurred well before the
      loss of vision, consistent with this increase in repertoire size constituting a
      preadaptive trait that conceivably could compensate to some extent for the lack
      of visual cues.

PMID- 30295712
TI  - Analysis of Triacylglycerols in Castor Oil Through Liquid Chromatography-Mass
      Spectrometry Based on Fourier Transform-Ion Cyclotron Resonance-Mass Spectrometry
      and Gas Chromatography-Mass Spectrometry.
AB  - Castor oil is a traditional Chinese medicine containing a chemically complex
      mixture of triacylglycerols (TAGs). Herein, the TAGs in castor oil were analyzed
      in detail. First, the fatty acid composition of castor oil was examined via
      methylated derivatisation followed by gas chromatography-mass spectrometry (GC
      MS). Then, using the fatty acid composition data, liquid chromatography-mass
      spectrometry (LC-MS) was applied to analyze the composition and relative content
      of TAGs. Nine TAGs were identified, wherein triricinolein (RRR) constituted ~81%
      of the total TAG content based on the peak areas. However, the TAGs in castor oil
      contain hydroxyl groups, which are incompatible with the equivalent carbon number
      (ECN) rule. Thus, an extended-ECN rule was expressed as E-ECN = CN (carbon
      number)-2.DB (double-bond number)-6.OH (hydroxyl group number) to characterize
      the retention of hydroxyl-containing TAGs in HPLC using a C18 column. Moreover,
      hydroxyl-containing TAGs may become dehydrated when analyzed using atmospheric
      pressure chemical ionization (APCI), which was confirmed via APCI Fourier
      transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS). Thus, the TAGs
      in castor oil were accurately identified through LC-MS together with FT-ICR-MS
      and GC-MS.

PMID- 30295713
TI  - Early Adolescence is a Critical Period for the Maturation of Inhibitory Behavior.
AB  - Psychiatric conditions marked by impairments in cognitive control often emerge
      during adolescence, when the prefrontal cortex (PFC) and its inputs undergo
      structural and functional maturation and are vulnerable to disruption by external
      events. It is not known, however, whether there exists a specific temporal window
      within the broad range of adolescence when the development of PFC circuitry and
      its related behaviors are sensitive to disruption. Here we show, in male mice,
      that repeated exposure to amphetamine during early adolescence leads to impaired
      behavioral inhibition, aberrant PFC dopamine connectivity, and reduced PFC
      dopamine function in adulthood. Remarkably, these deficits are not observed
      following exposure to the exact same amphetamine regimen at later times. These
      findings demonstrate that there is a critical period for the disruption of the
      adolescent maturation of cognitive control and PFC dopamine function and suggest
      that early adolescence is particularly relevant to the emergence of
      psychopathology in humans.

PMID- 30295714
TI  - Yap is Required for Scar Formation but not Myocyte Proliferation During Heart
      Regeneration in Zebrafish.
AB  - Aims: The Hippo signaling pathway regulates multiple cellular processes during
      organ development and maintenance by modulating activity of the transcriptional
      cofactor Yap. Core components of this pathway are required for neonatal mouse
      heart regeneration, however, investigations to date have typically focused on
      expression and activity in cardiomyocytes. Due to the regenerative capacity of
      zebrafish and the fact that global loss of Yap is not fully embryonic lethal in
      zebrafish, we leveraged a yap null mutant to investigate the impact of
      constitutive Yap deletion during zebrafish heart regeneration. Methods and
      Results: Following cryoinjury in adult hearts, myocyte proliferation was not
      decreased in yap mutants, contrary to expectations based on mouse data.
      Experiments in larval zebrafish (Danio rerio) revealed that deletion of either
      Yap or Taz had a modest effect on heart growth, reducing gross organ size, while
      their combined deletion was synergistic; thus, Yap and Taz share some overlapping
      roles in zebrafish heart development. Surprisingly, adult yap mutants exhibited
      decreased collagen composition at 7 days post injury, suggesting a critical role
      for Yap in scar formation during heart regeneration. siRNA-mediated Yap knockdown
      in primary rat (Rattus norvegicus) cardiac cells revealed a fibroblast-specific
      role for Yap in controlling the expression of cytoskeletal and myofibroblast
      activation genes, as well as pro-inflammatory cyto/chemokines. Corroborating
      these RNAseq data, we observed increased macrophage infiltration in the scars of
      yap mutants at 7 days post injury. Conclusions: These results suggest that Yap
      deletion has minimal effect on myocyte proliferation in adults, but significantly
      influences scar formation and immune cell infiltration during zebrafish heart
      regeneration. Collectively, these data suggest an unexpected role for Yap in
      matrix formation and macrophage recruitment during heart regeneration.

PMID- 30295715
TI  - Food impaction: etiology over 35 years and association with eosinophilic
      esophagitis.
AB  - With the emergence of eosinophilic esophagitis (EoE) as a common cause of food
      impaction (FI) and a presumed increase in incidence of EoE in the population, the
      effect on the incidence of FI has not been well described. The aim of this study
      is to describe the incidence of FI and endoscopic findings in these patients and
      the association with EoE. A population-based retrospective chart review of the
      Rochester Epidemiology Project database was performed to identify all patients
      within Olmsted County that presented with FI from 1976 to 2012. A review of all
      endoscopic findings, biopsy results, and demographic data was performed. 497
      patients were identified with FI from 1976 to 2012. The overall incidence of FI
      has changed from 1976 to 2012 (Fig. 1) (P < 0.001). The peak incidence of 17.12
      per 100,000 people occurred in the time period 1995 to 2000. Both the incidence
      of comorbid gastroesophageal reflux disease (GERD) and proton pump inhibitor
      (PPI) use increased over the time period of the study (P < 0.001 for both). Of
      these patients, 188 (46.7%) had no abnormalities on their endoscopy. The most
      common endoscopic finding was stricture in 71 (17.6%) patients followed closely
      by Schatzki's ring in 68 (16.9%) patients. 139 patients had biopsies performed
      within 2 years of FI and 50 (36.0%) of those were diagnosed with EoE. We present
      for the first time the changing incidence of FI over the last 35 years in a
      population-based setting. We also demonstrate the rise of EoE as an important
      clinical consideration in patients with FI.

PMID- 30295716
TI  - High Sensitivity Mapping of Cortical Dopamine D2 Receptor Expressing Neurons.
AB  - Cortical D2 dopamine receptor (Drd2) have mostly been examined in the context of
      cognitive function regulation and neurotransmission modulation of medial
      prefrontal cortex by principal neurons and parvalbumin positive, fast-spiking,
      interneurons in schizophrenia. Early studies suggested the presence of D2
      receptors in several cortical areas, albeit with major technical limitations. We
      used combinations of transgenic reporter systems, recombinase activated viral
      vectors, quantitative translatome analysis, and high sensitivity in situ
      hybridization to identify D2 receptor expressing cells and establish a map of
      their respective projections. Our results identified previously uncharacterized
      clusters of D2 expressing neurons in limbic and sensory regions of the adult
      mouse brain cortex. Characterization of these clusters by translatome analysis
      and cell type specific labeling revealed highly heterogeneous expression of D2
      receptors in principal neurons and various populations of interneurons across
      cortical areas. Transcript enrichment analysis also demonstrated variable levels
      of D2 receptor expression and several orphan G-protein-coupled receptors
      coexpression in different neuronal clusters, thus suggesting strategies for
      genetic and therapeutic targeting of D2 expressing neurons in specific cortical
      areas. These results pave the way for a thorough re-examination of cortical D2
      receptor functions, which could provide information about neuronal circuits
      involved in psychotic and mood disorders.

PMID- 30295717
TI  - Saccadic Adaptation Boosts Ongoing Gamma Activity in a Subsequent
      Visuoattentional Task.
AB  - Attention and saccadic adaptation (SA) are critical components of visual
      perception, the former enhancing sensory processing of selected objects, the
      latter maintaining the eye movements accuracy toward them. Recent studies
      propelled the hypothesis of a tight functional coupling between these mechanisms,
      possibly due to shared neural substrates. Here, we used magnetoencephalography to
      investigate for the first time the neurophysiological bases of this coupling and
      of SA per se. We compared visual discrimination performance of 12 healthy
      subjects before and after SA. Eye movements and magnetic signals were recorded
      continuously. Analyses focused on gamma band activity (GBA) during the pretarget
      period of the discrimination and the saccadic tasks. We found that GBA increases
      after SA. This increase was found in the right hemisphere for both postadaptation
      saccadic and discrimination tasks. For the latter, GBA also increased in the left
      hemisphere. We conclude that oculomotor plasticity involves GBA modulation within
      an extended neural network which persists after SA, suggesting a possible role of
      gamma oscillations in the coupling between SA and attention.

PMID- 30295718
TI  - Document triage for identifying protein-protein interactions affected by
      mutations: a neural network ensemble approach.
AB  - The precision medicine (PM) initiative promises to identify individualized
      treatment depending on a patients' genetic profile and their related responses.
      In order to help health professionals and researchers in the PM endeavor,
      BioCreative VI organized a PM Track to mine protein-protein interactions (PPI)
      affected by genetic mutations from the biomedical literature. In this paper, we
      present a neural network ensemble approach to identify relevant articles
      describing PPI affected by mutations. In this approach, several neural network
      models are used for document triage, and the ensemble performs better than any
      individual model. In the official runs, our best submission achieves an F-score
      of 69.04% in the BioCreative VI PM document triage task. After post-challenge
      analysis, to address the problem of the limited size of training set, a PPI pre
      trained module is incorporated into our approach to further improve the
      performance. Finally, our best ensemble method achieves an F-score of 71.04% on
      the test set.

PMID- 30295719
TI  - Tripal Developer Toolkit.
AB  - Tripal community database construction toolkit utilizing the content management
      system Drupal. Tripal is used to make biological, genetic and genomic data more
      discoverable, shareable, searchable and standardized. As funding for community
      level genomics databases declines, Tripal's open-source codebase provides a means
      for sites to be built and maintained with a minimal investment in staff and new
      development. Tripal is ultimately as strong as the community of sites and
      developers that use it. We present a set of developer tools that will make
      building and maintaining Tripal 3 sites easier for new and returning users. These
      tools break down barriers to entry such as setting up developer and testing
      environments, acquiring and loading test datasets, working with controlled
      vocabulary terms and writing new Drupal classes.

PMID- 30295720
TI  - A survey of ontology learning techniques and applications.
AB  - Ontologies have gained a lot of popularity and recognition in the semantic web
      because of their extensive use in Internet-based applications. Ontologies are
      often considered a fine source of semantics and interoperability in all
      artificially smart systems. Exponential increase in unstructured data on the web
      has made automated acquisition of ontology from unstructured text a most
      prominent research area. Several methodologies exploiting numerous techniques of
      various fields (machine learning, text mining, knowledge representation and
      reasoning, information retrieval and natural language processing) are being
      proposed to bring some level of automation in the process of ontology acquisition
      from unstructured text. This paper describes the process of ontology learning and
      further classification of ontology learning techniques into three classes
      (linguistics, statistical and logical) and discusses many algorithms under each
      category. This paper also explores ontology evaluation techniques by highlighting
      their pros and cons. Moreover, it describes the scope and use of ontology
      learning in several industries. Finally, the paper discusses challenges of
      ontology learning along with their corresponding future directions.

PMID- 30295721
TI  - Effect of preoperative inspiratory muscle training on physical functioning
      following esophagectomy.
AB  - This study aims to examine the effect of preoperative inspiratory muscle training
      (IMT) on pre- and postoperative functional exercise performance in patients
      undergoing esophagectomy. A subcohort of patients recruited to the PREPARE
      randomized control trial were studied. Following evaluation of respiratory muscle
      function (spirometry, maximum inspiratory pressure (MIP), and inspiratory muscle
      endurance), postoperative mobilization (accelerometry) and postoperative physical
      functioning (6-minute walk test (6MWT)), participants scheduled for esophagectomy
      were randomly assigned to either 2 weeks of preoperative IMT or a control group.
      Measures were repeated on the day before surgery and postoperatively. Sixty
      participants (mean (standard deviation) age 64.13 (7.8) years; n = 42 male; n =
      43 transthoracic esophagectomy; n = 17 transhiatial esophagectomy) were included
      in the final analysis (n = 28 IMT; n = 32 control). There was a significant
      improvement in preoperative MIP (P = 0.03) and inspiratory muscle endurance (P =
      0.04); however preoperative 6MWT distance did not change. Postoperatively,
      control participants were more active on postoperative day (POD)1, and from POD1
      POD5 (P = 0.04). Predischarge, 6MWT distance was significantly lower in the IMT
      group (305.61 (116.3) m) compared to controls (380.2 (47.1) m, P = 0.03). Despite
      an increase in preoperative respiratory muscle function, preoperative IMT does
      not improve pre- or postoperative physical functioning or postoperative
      mobilization following esophagectomy.

PMID- 30295722
TI  - Death-Domain-Receptor 3 Deletion Normalizes Inflammatory Gene Expression and
      Prevents Ileitis in Experimental Crohn's Disease.
AB  - Background: TNF-like cytokine 1A (TL1A) and its functional receptor, death-domain
      receptor-3 (DR3), are multifunctional mediators of effector and regulatory
      immunity. We aimed to evaluate the functional role and therapeutic potential of
      TL1A/DR3 signaling in Crohn's disease-like ileitis. Methods: Ileitis-prone
      SAMP1/YitFc (SAMP) and TNFDeltaARE/+ mice were rendered deficient for DR3 or TL1A
      by microsatellite marker-assisted backcrossing. Pathological and immunological
      characteristics were compared between control and knockout mice, and mucosal
      immunophenotype was analyzed by Nanostring microarray assay. The therapeutic
      effect of pharmacological TL1A neutralization was also investigated. Results: DR3
      deficiency was associated with restoration of a homeostatic mucosal immunostat in
      SAMP mice through the regulation of several pro- and anti-inflammatory genes.
      This led to suppression of effector immunity, amelioration of ileitis severity,
      and compromised ability of either unfractionated CD4+ or CD4+CD45RBhi mucosal
      lymphocytes to transfer ileitis to severe combined immunodeficient mice
      recipients. TNF-driven ileitis was also prevented in TNFDeltaARE/+xDR3-/- mice,
      in association with decreased expression of the pro-inflammatory cytokines TNF
      and IFN-gamma. In contrast to DR3, TL1A was dispensable for the development of
      ileitis although it affected the kinetics of inflammation, as TNFDeltaARE/+xTL1A
      /- demonstrated delayed onset of inflammation, whereas administration of a
      neutralizing, anti-TL1A antibody ameliorated early but not late TNFDeltaARE/+
      ileitis. Conclusion: We found a prominent pro-inflammatory role of DR3 in chronic
      ileitis, which is only partially mediated via interaction with TL1A, raising the
      possibility for additional DR3 ligands. Death-domain-receptor-3 appears to be a
      master regulator of mucosal homeostasis and inflammation and may represent a
      candidate therapeutic target for chronic inflammatory conditions of the bowel.

PMID- 30295723
TI  - Soil amendment with sewage sludge affects soil prokaryotic community composition,
      mobilome and resistome.
AB  - Municipal sewage sludge (MSS) is often directly applied to fields despite
      concerns regarding the spread of harmful microbes and associated resistance genes
      (RGs). In this four month microcosm study, the dynamics of prokaryotic
      communities in agricultural soil and changes in mobile genetic elements and RGs
      following amendment with stabilized MSS were investigated. TaqMan-based
      quantitative real-time (q)PCR showed that RG prevalence was high when compared to
      untreated soil and genes for class 1 integrons (intI1), streptomycin RGs (aadA,
      strA) and tetracycline RG (tet(W)) were detectable for the duration of the four
      month study. High-throughput qPCR revealed an enhanced prevalence of
      aminoglycoside RGs (aacC, aadE), macrolide lincosamide-streptogramin B RGs (ermB,
      ermF) and tetracycline RGs (tet(L), tet(M), tet(X)). Illumina MiSeq sequencing of
      16S rRNA gene fragments amplified from total community DNA revealed significant
      changes in the prokaryotic community composition both at phylum and genus levels,
      with lower richness and evenness after MSS amendment followed by gradual recovery
      after 119 days. Conjugative plasmids captured from MSS using exogenous isolation
      belonged predominantly to the IncP-1 plasmid group. Our results provide new
      insights into short- and medium-term effects of MSS amendment on soil prokaryotic
      communities, including the mobilome and resistome.

PMID- 30295724
TI  - Extracting chemical-protein relations using attention-based neural networks.
AB  - Relation extraction is an important task in the field of natural language
      processing. In this paper, we describe our approach for the BioCreative VI Task
      5: text mining chemical-protein interactions. We investigate multiple deep neural
      network (DNN) models, including convolutional neural networks, recurrent neural
      networks (RNNs) and attention-based (ATT-) RNNs (ATT-RNNs) to extract chemical
      protein relations. Our experimental results indicate that ATT-RNN models
      outperform the same models without using attention and the ATT-gated recurrent
      unit (ATT-GRU) achieves the best performing micro average F1 score of 0.527 on
      the test set among the tested DNNs. In addition, the result of word-level
      attention weights also shows that attention mechanism is effective on selecting
      the most important trigger words when trained with semantic relation labels
      without the need of semantic parsing and feature engineering. The source code of
      this work is available at https://github.com/ohnlp/att-chemprot.

PMID- 30295725
TI  - Toward a service-based workflow for automated information extraction from
      herbarium specimens.
AB  - Over the past years, herbarium collections worldwide have started to digitize
      millions of specimens on an industrial scale. Although the imaging costs are
      steadily falling, capturing the accompanying label information is still
      predominantly done manually and develops into the principal cost factor. In order
      to streamline the process of capturing herbarium specimen metadata, we specified
      a formal extensible workflow integrating a wide range of automated specimen image
      analysis services. We implemented the workflow on the basis of OpenRefine
      together with a plugin for handling service calls and responses. The evolving
      system presently covers the generation of optical character recognition (OCR)
      from specimen images, the identification of regions of interest in images and the
      extraction of meaningful information items from OCR. These implementations were
      developed as part of the Deutsche Forschungsgemeinschaft-funded a standardised
      and optimised process for data acquisition from digital images of herbarium
      specimens (StanDAP-Herb) Project.

PMID- 30295726
TI  - Accurate Detection of Chimeric Contigs via Bionano Optical Maps.
AB  - Summary: A chimeric contig is contig that has been incorrectly assembled, i.e., a
      contig that contains one or more mis-joins. The detection of chimeric contigs can
      be carried out either by aligning assembled contigs to genome-wide maps (e.g.,
      genetic, physical or optical maps) or by mapping sequenced reads to the assembled
      contigs. Here we introduce a software tool called Chimericognizer that takes
      advantage of one or more Bionano Genomics optical maps to accurately detect and
      correct chimeric contigs. Experimental results show that Chimericognizer is very
      accurate, and significantly better than the chimeric detection method offered by
      the Bionano Hybrid Scaffold pipeline. Chimericognizer can also detect and correct
      chimeric optical molecules. Availability:
      https://github.com/ucrbioinfo/Chimericognizer. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30295727
TI  - Geotrichum candidum gene expression and metabolite accumulation inside the cells
      reflect the strain oxidative stress sensitivity and ability to produce flavour
      compounds.
AB  - Geotrichum candidum is a fungus-like yeast widely used as a starter culture for
      cheese ripening for its proteolytic and lipolytic activities and its contribution
      to the cheese flavours. The sequenced strain G. candidum CLIB 918 was isolated
      from cheese Pont-L'Eveque. This strain's ability to produce volatile compounds
      was compared to the ability of a known strong sulphur compound producer G.
      candidum strain (Gc203). The aminotransferase-coding genes BAT2 and ARO8 were
      identified to be involved in methionine catabolism. The production of volatile
      compounds indicated that the sequenced strain was a moderate producer compared to
      the strong producer strain. The major volatile compounds were produced from
      sulphur amino acid, branched-chain amino acid and fatty acid metabolisms.
      Metabolite content of the cells showed that the ability of the strain to produce
      volatile compounds was inversely proportional to its ability to store amino acids
      inside the cells. Reduced glutathione, hypotaurine and taurine intracellular
      concentrations and volatile fatty aldehyde production indicated the role of
      oxidative stress sensitivity in flavour production. The increase in expression of
      several genes in a Reblochon-type cheese at the end of ripening confirmed that
      oxygen and iron were key factors regulating cheese flavour production.

PMID- 30295728
TI  - DIGREM: an integrated web-based platform for detecting effective multi-drug
      combinations.
AB  - Motivation: Synergistic drug combinations are a promising approach to achieve a
      desirable therapeutic effect in complex diseases through the multi-target
      mechanism. However, in vivo screening of all possible multi-drug combinations
      remains cost-prohibitive. An effective and robust computational model to predict
      drug synergy in silico will greatly facilitate this process. Results: We
      developed DIGREM (Drug-Induced Genomic Response models for identification of
      Effective Multi-drug combinations), an online tool kit that can effectively
      predict drug synergy. DIGREM integrates DIGRE, IUPUI_CCBB, gene set-based and
      correlation-based models for users to predict synergistic drug combinations with
      dose response information and drug-treated gene expression profiles.
      Availability: http://lce.biohpc.swmed.edu/drugcombination. Supplementary
      information: Supplementary data is available at Bioinformatics online.

PMID- 30295729
TI  - The Effectiveness of the Positive Mood and Active Life Program on Reducing
      Depressive Symptoms in Long-term Care Facilities.
AB  - Background and Objectives: Depression is prevalent among long-term care facility
      (LTCF) residents. However, interventions are not normally part of the management
      of these residents due to a shortage of mental health professionals. On the basis
      of Lewinsohn's behavioral model of depression, we developed a 12-week pleasant
      activity scheduling intervention, the Positive Mood and Active Life (PMAL)
      program. This study evaluated the effectiveness of the PMAL program on reducing
      depressive symptoms and improving quality of life among at-risk LTCF residents.
      Research Design and Methods: We adopted a cluster randomized controlled trial
      design. Four LTCFs were randomly assigned as treatment sites and three provided
      care as usual. At-risk LTCF residents (N = 68) were identified using the Mood
      Resident Assessment Protocol from the Minimum Data Set 2.0. The PMAL program was
      delivered to 34 residents. The primary and secondary outcomes were depressive
      symptoms and quality of life, as measured by the Geriatric Depression Scale-15
      (GDS-15) and the World Health Organization Quality of Life scale-BREF (WHOQoL
      BREF), respectively. Results: After 12 weeks, the GDS-15 score in the
      intervention group showed a reduction from 7.59 to 5.67, with a significant
      treatment by time effect (p = .006), based on the mixed model analysis; the
      WHOQoL-BREF score also substantially increased from 69.83 to 86.61 (p = .000).
      Discussion and Implications: The PMAL program is effective in reducing depressive
      symptoms of at-risk LTCF residents. It is a feasible intervention that requires
      minimum resources and can be integrated with standardized assessment systems.

PMID- 30295730
TI  - VIRULIGN: fast codon-correct alignment and annotation of viral genomes.
AB  - Summary: Virus sequence data are an essential resource for reconstructing
      spatiotemporal dynamics of viral spread as well as to inform treatment and
      prevention strategies. However, the potential benefit for these applications
      critically depends on accurate and correctly annotated alignments of genetically
      heterogeneous data. VIRULIGN was built for fast codon-correct alignments of large
      datasets, with standardized and formalized genome annotation and various
      alignment export formats. Availability and implementation: VIRULIGN is freely
      available at https://github.com/rega-cev/virulign as an open source software
      project. Supplementary information: Supplementary data is available at
      Bioinformatics online.

PMID- 30295731
TI  - Mifepristone treatment prior to insertion of a levonorgestrel releasing
      intrauterine system for improved bleeding control - a randomized controlled
      trial.
AB  - STUDY QUESTION: Does pre-treatment with a low dose of mifepristone improve
      irregular vaginal bleeding patterns during the initial 3 months after LNG-IUS
      placement? SUMMARY ANSWER: Mifepristone treatment prior to LNG-IUS insertion
      results in significantly lower bleeding and spotting rates for the first month
      post insertion but no significant reduction at 3 months post insertion. WHAT IS
      KNOWN ALREADY: One of the leading causes of premature discontinuation of the LNG
      IUS is unscheduled bleeding in the first months following its insertion. Up to
      now, there has been no effective treatment to prevent this side effect which
      reduces continuation rates for one of the most effective contraceptives. STUDY
      DESIGN, SIZE, DURATION: This randomized, double blinded, controlled trial was
      conducted between 2009 and 2015. In total, 68 women opting for a LNG-IUS were
      screened for eligibility, of whom 58 were randomized at a ratio of 1:1 in blocks
      of 10 to pre-treatment with mifepristone or a comparator. The main outcome was
      the rate of bleeding and spotting days reported during the first 3 months post
      LNG-IUS 52 mg placement. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthy women
      with regular and normal menstrual cycles aged 18-43 years were enrolled at a
      single center in a university hospital; 29 were allocated to 2 months pre
      treatment with a low dose mifepristone and 29 to the comparator prior to
      insertion of the LNG-IUS. Women were advised to use barrier methods during the
      pre-treatment period. Bleeding diaries were collected for the pre-treatment
      period and for the first 6 months after the LNG-IUS placement. MAIN RESULTS AND
      THE ROLE OF CHANCE: There were no differences in demographic or baseline
      characteristics between the study groups. Data for analysis of the main outcome
      were contributed by a per protocol population of 19 women per group. There was a
      significant lower bleeding and spotting rate in the mifepristone group (-17.8%
      points, P < 0.001) after 2 months of pre-treatment and during the first month
      after the LNG-IUS insertion. In the following months, no significant difference
      could be seen. While no pregnancies occurred prior to LNG-IUS insertion in the
      mifepristone group, there were three unintended pregnancies in the comparator
      group which emphasizes the need for a reliable contraceptive potential in any pre
      treatment regimen used in clinical practice. LIMITATIONS, REASONS FOR CAUTION:
      The use of mifepristone prior to the LNG-IUS insertion in this trial was used as
      prophylaxis against unscheduled bleeding after the placement of the device.
      Although this side effect constitutes a major concern in a clinical setting, only
      a subset of women are at risk. This is the first study using pre-treatment to
      attempt improved bleeding control. The differences were small and the effect was
      short lasting but the reduced rate of bleeding and spotting observed during the
      first month following LNG-IUS insertion indicates that this approach may be
      further explored. The fact that there were three pregnancies in the comparator
      group stresses the need for any pre-treatment to also protect against unplanned
      pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: Modified treatment protocols of
      mifepristone could be used prior to the LNG-IUS insertion to investigate possible
      further improvement of the outcome. The effect size of the current dose used
      might have been more prominent in women with LNG-IUS if the treatment also
      continued some weeks after the placement of the device. Although the low dose of
      mifepristone used in this trial is not available in Europe, other progesterone
      receptor modulators currently available could be investigated in larger clinical
      trials. To avoid unintended pregnancy in the pretreatment period, the dosage used
      should, ideally, also be effective for contraception and the pretreatment period
      should be kept as short as possible. STUDY FUNDING/COMPETING INTEREST(S): This
      study was funded by the Swedish Research Council (2012-2844, 2017-00932),
      Stockholm County Council and Karolinska Institutet (ALF). Conflicts of interests
      for K.G.D. and H.K.K. are listed at the end of the paper. The other authors have
      no conflicts of interest. TRIAL REGISTRATION NUMBER: EudraCT number 2009-009014
      40. Regional ethical review board at Karolinska Institutet permit 2009/144-31/4.
      TRIAL REGISTRATION DATE: 20 July 2009. DATE OF FIRST PATIENT'S ENROLMENT: 24
      November 2009.

PMID- 30295732
TI  - Expression dynamics of the poly-gamma-glutamic acid biosynthesis genes of
      Bacillus subtilis in response to glucose and glutamic acid-a pilot study.
AB  - Poly-gamma-glutamic acid (PGA) is biosynthesized by various Bacillus species
      through PGA synthetase, encoded by the PGA operon comprised of the ywsC and
      ywtABC genes. Due to the minimal available knowledge, understanding the
      expression pattern of PGA operon genes is pivotal. In this study, the effect of
      glucose and glutamic acid on the global gene expression profile of Bacillus
      subtilis Natto3 was investigated using high throughput microarray, with an
      emphasis on the PGA operon and genes influencing PGA production. Two treatment
      groups (set1-in the presence of glutamic acid and set2-in the presence of
      glutamic acid + glucose) were analyzed against the control (in the presence of
      glucose). In the microarray, both the groups showed a trend of up-regulation for
      ywsC and ywtA genes (log2 fold change of 0.55, P = 0.0194, 0.92, P = 0.0069 in
      set1 and 0.78, P = 0.0023, 0.59, P = 0.0172 in set2, respectively) and down
      regulation of ywtB and ywtC genes (log2 fold change of -1.83, P = 0.0001, -1.42,
      P = 0.0017 in set1 and -1.52, P = 0.0012, -0.55, P = 0.1112 in set2,
      respectively), supporting the indispensability of the ywsC and ywtA genes in PGA
      production. Interestingly, the ywtB and ywtC genes, belonging to the same operon,
      were down-regulated in both the conditions (set1 and set2). To the best of our
      knowledge, this expression pattern of PGA operon genes is a unique observation.

PMID- 30295733
TI  - A Data-Based Hypothesis That Inflammatory Bowel Disease Unclassified (IBD-U) May
      Indicate That IBD Is a Spectrum of a Single Infectious Intestinal Disease.

PMID- 30295734
TI  - JMJD3 and vascular injury: the Emperor's new clothes.

PMID- 30295735
TI  - Response to the Letter from Drs. Greenstein and Brown.

PMID- 30295737
TI  - CoMM: a collaborative mixed model to dissecting genetic contributions to complex
      traits by leveraging regulatory information.
AB  - Motivation: Genome-wide association studies (GWASs) have been successful in
      identifying many genetic variants associated with complex traits. However, the
      mechanistic links between these variants and complex traits remain elusive. A
      scientific hypothesis is that genetic variants influence complex traits at the
      organismal level via affecting cellular traits, such as regulating gene
      expression and altering protein abundance. Although earlier works have already
      presented some scientific insights about this hypothesis and their findings are
      very promising, statistical methods that effectively harness multilayered data
      (e.g., genetic variants, cellular traits and organismal traits) on a large scale
      for functional and mechanistic exploration are highly demanding. Results: In this
      study, we propose a collaborative mixed model (CoMM) to investigate the
      mechanistic role of associated variants in complex traits. The key idea is built
      upon the emerging scientific evidence that genetic effects at the cellular level
      are much stronger than those at the organismal level. Briefly, CoMM combines two
      models: the first model relating gene expression with genotype and the second
      model relating phenotype with predicted gene expression using the first model.
      The two models are fitted jointly in CoMM, such that the uncertainty in
      predicting gene expression has been fully accounted. To demonstrate the
      advantages of CoMM over existing methods, we conducted extensive simulation
      studies, and also applied CoMM to analyze 25 traits in NFBC1966 and Genetic
      Epidemiology Research on Aging (GERA) studies by integrating transcriptome
      information from the Genetic European in Health and Disease (GEUVADIS) Project.
      The results indicate that by leveraging regulatory information, CoMM can
      effectively improve the power of prioritizing risk variants. Regarding the
      computational efficiency, CoMM can complete the analysis of NFBC1966 data set and
      GERA data sets in 2 minutes and 18 minutes, respectively. Availability and
      implementation: The developed R package is available at
      https://github.com/gordonliu810822/CoMM. Supplementary Information: Supplementary
      data are available at Bioinformatics online.

PMID- 30295736
TI  - Endometrial receptivity revisited: endometrial transcriptome adjusted for tissue
      cellular heterogeneity.
AB  - STUDY QUESTION: Does cellular composition of the endometrial biopsy affect the
      gene expression profile of endometrial whole-tissue samples? SUMMARY ANSWER: The
      differences in epithelial and stromal cell proportions in endometrial biopsies
      modify the whole-tissue gene expression profiles and affect the results of
      differential expression analyses. WHAT IS ALREADY KNOWN: Each cell type has its
      unique gene expression profile. The proportions of epithelial and stromal cells
      vary in endometrial tissue during the menstrual cycle, along with individual and
      technical variation due to the method and tools used to obtain the tissue biopsy.
      STUDY DESIGN, SIZE, DURATION: Using cell-population specific transcriptome data
      and computational deconvolution approach, we estimated the epithelial and stromal
      cell proportions in whole-tissue biopsies taken during early secretory and mid
      secretory phases. The estimated cellular proportions were used as covariates in
      whole-tissue differential gene expression analysis. Endometrial transcriptomes
      before and after deconvolution were compared and analysed in biological context.
      PARTICIPANTS/MATERIAL, SETTING, METHODS: Paired early- and mid-secretory
      endometrial biopsies were obtained from 35 healthy, regularly cycling, fertile
      volunteers, aged 23-36 years, and analysed by RNA sequencing. Differential gene
      expression analysis was performed using two approaches. In one of them,
      computational deconvolution was applied as an intermediate step to adjust for the
      proportions of epithelial and stromal cells in the endometrial biopsy. The
      results were then compared to conventional differential expression analysis. Ten
      paired endometrial samples were analysed with qPCR to validate the results. MAIN
      RESULTS AND THE ROLE OF CHANCE: The estimated average proportions of stromal and
      epithelial cells in early secretory phase were 65% and 35%, and during mid
      secretory phase, 46% and 54%, respectively, correlating well with the results of
      histological evaluation (r = 0.88, P = 1.1 * 10-6). Endometrial tissue
      transcriptomic analysis showed that approximately 26% of transcripts (n = 946)
      differentially expressed in receptive endometrium in cell-type unadjusted
      analysis also remain differentially expressed after adjustment for biopsy
      cellular composition. However, the other 74% (n = 2645) become statistically non
      significant after adjustment for biopsy cellular composition, underlining the
      impact of tissue heterogeneity on differential expression analysis. The results
      suggest new mechanisms involved in endometrial maturation, involving genes like
      LINC01320, SLC8A1 and GGTA1P, described for the first time in context of
      endometrial receptivity. LARGE-SCALE DATA: The RNA-seq data presented in this
      study is deposited in the Gene Expression Omnibus database with accession number
      GSE98386. LIMITATIONS REASONS FOR CAUTION: Only dominant endometrial cell types
      were considered in gene expression profile deconvolution; however, other less
      frequent endometrial cell types also contribute to the whole-tissue gene
      expression profile. WIDER IMPLICATIONS OF THE FINDINGS: The better understanding
      of molecular processes during transition from pre-receptive to receptive
      endometrium serves to improve the effectiveness and personalization of assisted
      reproduction protocols. Biopsy cellular composition should be taken into account
      in future endometrial 'omics' studies, where tissue heterogeneity could
      potentially influence the results. STUDY FUNDING/COMPETING INTEREST(S): This
      study was funded by: Estonian Ministry of Education and Research (grant IUT34
      16); Enterprise Estonia (EU48695); the EU-FP7 Eurostars program (NOTED, EU41564);
      the EU-FP7 Marie Curie Industry-Academia Partnerships and Pathways (SARM,
      EU324509); Horizon 2020 innovation program (WIDENLIFE, EU692065); MSCA-RISE-2015
      project MOMENDO (No 691058) and the Miguel Servet Program Type I of Instituto de
      Salud Carlos III (CP13/00038); Spanish Ministry of Economy, Industry and
      Competitiveness (MINECO) and European Regional Development Fund (FEDER): grants
      RYC-2016-21199 and ENDORE SAF2017-87526. Authors confirm no competing interests.

PMID- 30295738
TI  - Emergence of Escherichia coli ST131 H30/H30-Rx subclones in companion animals.

PMID- 30295739
TI  - RAD9A promotes metastatic phenotypes through transcriptional regulation of
      Anterior Gradient 2 (AGR2).
AB  - RAD9A plays an important role in prostate tumorigenesis and metastasis related
      phenotypes. The protein classically functions as part of the RAD9A-HUS1-RAD1
      complex but can also act independently. RAD9A can selectively transactivate
      multiple genes, including CDKN1A and NEIL1 by binding p53-consensus sequences in
      or near promoters. RAD9A is overexpressed in human prostate cancer specimens and
      cell lines; its expression correlates with tumor progression. Silencing RAD9A in
      prostate cancer cells impairs their ability to form tumors in vivo and migrate as
      well as grow anchorage-independently in vitro. We demonstrate herein that RAD9A
      transcriptionally controls AGR2, a gene aberrantly overexpressed in patients with
      metastatic prostate cancer. Transient or stable knockdown of RAD9A in PC-3 cells
      caused downregulation of AGR2 protein abundance. Reduced AGR2 protein levels were
      due to lower abundance of AGR2 mRNA. The AGR2 genomic region upstream of the
      coding initiation site contains several p53 consensus sequences. RAD9A bound
      specifically to the 5'-untranslated region of AGR2 in PC-3 cells at a partial p53
      consensus sequence at position +3136 downstream from the transcription start
      site, determined by chromatin immunoprecipitation, followed by PCR amplification.
      Binding of RAD9A to the p53 consensus sequence was sufficient to drive AGR2 gene
      transcription, shown by a luciferase reporter assay. In contrast, when the RAD9A
      binding sequence on the AGR2 was mutated, no luciferase activity was detected.
      Knockdown of RAD9A in PC-3 cells impaired cell migration and anchorage
      independent growth. However, ectopically expressed AGR2 in RAD9A-depleted PC-3
      cells restored these phenotypes. Our results suggest RAD9A drives metastasis by
      controlling AGR2 abundance.

PMID- 30295740
TI  - Population pharmacokinetics of daptomycin in critically ill patients with various
      degrees of renal impairment.
AB  - Objectives: The objective of this study was to characterize the pharmacokinetics
      of unbound and total concentrations of daptomycin in infected ICU patients with
      various degrees of renal impairment. From these results, the probability of
      attaining antimicrobial efficacy and the risks of toxicity were assessed.
      Methods: Twenty-four ICU patients with various renal functions and requiring
      treatment of complicated skin and soft-tissue infections, bacteraemia, or
      endocarditis with daptomycin were recruited. Daptomycin (Cubicin(r)) at 10 mg/kg
      was administered every 24 h for patients with creatinine clearance (CLCR) >=30
      mL/min and every 48 h for patients with CLCR <30 mL/min. Total and unbound plasma
      concentrations and urine concentrations of daptomycin were analysed
      simultaneously following a population pharmacokinetic approach. Simulations were
      conducted to estimate the probability of attaining efficacy (unbound AUCu/MIC >40
      or >80) or toxicity (Cmin >24.3 mg/L) targets. Results: Exposure to unbound
      daptomycin increased when the renal function decreased, thus increasing the
      probability of reaching the efficacy targets, but also the risk of toxicity.
      Modifications of the unbound fraction (fu) of daptomycin did not affect the
      pharmacokinetics of unbound daptomycin, but did affect the pharmacokinetics of
      total daptomycin. Conclusions: Daptomycin at 10 mg/kg q24h allowed efficacy
      pharmacokinetic/pharmacodynamic targets for ICU patients with CLCR >=30 mL/min to
      be reached. For patients with CLCR <30 mL/min, halving the rate of drug
      administration, i.e. 10 mg/kg q48h, was sufficient to reach these targets. No
      adverse events were observed, but the toxicity of the 10 mg/kg q24h dosing
      regimen should be further assessed, particularly for patients with altered renal
      function.

PMID- 30295741
TI  - Eutopic stromal cells of endometriosis promote neuroangiogenesis via exosome
      pathway.
AB  - Endometriosis is a common multifactorial gynecological disorder defined as the
      proliferation of endometrial tissue outside of the uterine cavity.
      Neuroangiogenesis (co-recruitment of nerves and blood vessels) is believed to
      play an integral part in the establishment and growth of endometriotic lesions.
      We hypothesized that exosomes derived from abnormal endometrium may serve as the
      second identifier of endometriosis and play an important role in the development
      of endometriosis by regulating neuroangiogenesis. Primary human endometrial
      stromal cells (ESCs) were isolated from eutopic endometrium (EmESC, n = 22) with
      endometriosis and normal endometrium (CoESC, n = 6). Exosomes were isolated from
      ESCs using "standard" ultracentrifugation method, and the characterization of
      exosomes were identified through transmission electron microscopy, nanoparticle
      tracking analysis, and western blot. The role of exosomes in regulating
      neuroangiogenesis was determined through in vitro tube formation assay, neurite
      outgrowth assay, and dorsal root ganglion (DRG) neuron apoptosis analysis. The
      data showed that EmESCs could secrete exosomes with a diameter of approximately
      100 nm and a biconcave morphological feature; they were internalized by human
      umbilical vein endothelial cells (HUVECs) and DRG neurons and enhanced
      neuroangiogenic effects. We further validated the role of exosomes through
      blocking experiments. We found that when the exosome secretion was blocked, the
      pro-neuroangiogenesis effects were decreased. In conclusion, these data suggested
      that exosomes may play a key role in endometriosis by promoting
      neuroangiogenesis.

PMID- 30295742
TI  - HDL-C levels, CVD risk and cancer: a relation which does not apply to all?

PMID- 30295743
TI  - In vitro susceptibility of Salmonella enterica serovar Typhi to
      ceftolozane/tazobactam.

PMID- 30295744
TI  - QuagmiR: A Cloud-based Application for IsomiR Big Data Analytics.
AB  - Summary: MicroRNAs (miRNAs) function as master regulators of gene expression.
      Recent studies demonstrate that miRNA isoforms (isomiRs) play a unique role
      during cancer development. Here, we present QuagmiR, the first cloud-based tool
      to analyze isomiRs from next generation sequencing data. Using a novel and
      flexible searching algorithm designed for the detection and annotation of
      heterogeneous isomiRs, it permits extensive customization of the query process
      and reference databases to meet the user's diverse research needs. Availability
      and implementation: QuagmiR is written in Python and can be obtained freely from
      GitHub (https://github.com/Gu-Lab-RBL-NCI/QuagmiR). QuagmiR can be run from the
      command line on local machines, as well as on high-performance servers. A web
      accessible version of the tool has also been made available for use by academic
      researchers through the National Cancer Institute-funded Seven Bridges Cancer
      Genomics Cloud (https://cancergenomicscloud.org). Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30295745
TI  - cath-resolve-hits: a new tool that resolves domain matches suspiciously quickly.
AB  - Motivation: Many bioinformatics areas require us to assign domain matches onto
      stretches of a query protein. Starting with a set of candidate matches, we want
      to identify the optimal subset that has limited/no overlap between matches. This
      may be further complicated by discontinuous domains in the input data. Existing
      tools are increasingly facing very large data-sets for which they require
      prohibitive amounts of CPU-time and memory. Results: We present cath-resolve-hits
      (CRH), a new tool that uses a dynamic-programming algorithm implemented in open
      source C ++ to handle large data-sets quickly (up to ~1 million hits/second) and
      in reasonable amounts of memory. It accepts multiple input formats and provides
      its output in plain text, JSON or graphical HTML. We describe a benchmark against
      an existing algorithm, which shows CRH delivers very similar or slightly improved
      results and very much improved CPU/memory performance on large data-sets.
      Availability: CRH is available at https://github.com/UCLOrengoGroup/cath-tools;
      documentation is available at http://cath-tools.readthedocs.io. Supplementary
      information: Supplementary Material is available at Bioinformatics online.

PMID- 30295746
TI  - Novel high-throughput screening method using quantitative PCR to determine the
      antimicrobial susceptibility of Orientia tsutsugamushi clinical isolates.
AB  - Objectives: To develop a method to enable the large-scale antimicrobial
      susceptibility screening of Orientia tsutsugamushi clinical isolates, using one
      timepoint and one concentration of antibiotics to considerably speed up the time
      to result. Methods: Growth, harvesting, multiplicity of infection (moi) and the
      day to determine the MICs were optimized using five O. tsutsugamushi reference
      strains [susceptible (Karp, Kato and Gilliam) and putatively resistant (AFC-3 and
      AFSC-4)], one clinical isolate (UT76) and one rodent isolate (TA763).
      Subsequently, the MICs of azithromycin, chloramphenicol and doxycycline for these
      strains and 51 clinical isolates including AFSC-7 were determined. An optimal
      concentration was calculated using the epidemiological cut-off value. Results:
      The conditions for O. tsutsugamushi infection, growth and harvesting were
      determined to be an moi of 100:1 and trypsinization with the peak growth on day
      10. The resulting MICs were in line with previously published susceptibility data
      for all reference strains, except for Karp and AFSC-4, which showed azithromycin
      MICs of 0.0156 and 0.0313 mg/L, compared with 0.0078 and 0.0156 mg/L,
      respectively, in previous reports. The MIC of doxycycline for AFC-3 was 0.125
      mg/L compared with >4 mg/L in earlier reports. The final single screening
      concentrations were identified as: azithromycin, 0.125 mg/L; chloramphenicol, 8
      mg/L; and doxycycline, 1 mg/L. Conclusions: This simplified procedure facilitates
      the simultaneous screening of 48 isolates for actively monitoring potential
      resistance of this important fever pathogen, with an 8-fold throughput
      improvement over early methods. The data do not support the existence of
      doxycycline- and chloramphenicol-resistant scrub typhus.

PMID- 30295747
TI  - Mutual Regulation of TLR/NLR and CEACAM1 in the Intestinal Microvasculature:
      Implications for IBD Pathogenesis and Therapy.
AB  - Background: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)
      displays multiple activities, among which pathogen binding and angiogenesis are
      particularly prominent. These same functions are also exerted by Toll- and NOD
      like receptors (TLRs and NLRs), which are critical mediators of innate immune
      responses. We investigated whether a functional inter-relationship exists between
      CEACAM1 and TLRs and NLRs and its potential impact on induction of intestinal
      angiogenesis. Methods: This hypothesis was tested using human intestinal
      microvascular endothelial cells, a unique cell population exposed to microbial
      products under physiological and pathological conditions. Results: The results
      show that activation of TLR2/4, TLR4, NOD1, and NOD2 by specific bacterial
      ligands selectively and differentially upregulates the levels of cellular and
      soluble CEACAM1 produced by intestinal microvascular endothelial cells. The
      results also show that CEACAM1 regulates the migration, transmigration, and tube
      formation of these endothelial cells and mediates vessel sprouting induced by
      specific TLR and NLR bacterial ligands. Combined, these results demonstrate a
      close and reciprocal regulatory interaction between CEACAM1 and bacterial
      products in mediating multiple functions essential to new vessel formation in the
      gut mucosa. Conclusions: A coordinated and reciprocal interaction of CEACAM1 and
      microbiota-derived factors is necessary to optimize angiogenesis in the gut
      mucosa. This suggests that a coordination of endogenous and exogenous innate
      immune responses is necessary to promote intestinal angiogenesis under
      physiological and inflammatory conditions such as inflammatory bowel disease.

PMID- 30295748
TI  - Hybrid transgastric approach for the treatment of gastroesophageal junction
      pathologies.
AB  - Flexible endoscopy has evolved to the point that it includes many endoluminal
      procedures that once required open or laparoscopic surgery, for instance,
      antireflux surgery, pyloromyotomy, mucosal and submucosal tumor resections, and
      even full-thickness resection. However, these procedures remain technically
      demanding due to flexible technology issues: difficult imaging, limited energy
      devices, lack of staplers, unsatisfactory suturing abilities, and so on.
      Transgastric laparoscopy or hybrid laparoscopy/flex endoscopy has been described
      for almost two decades as an alternative to a pure endoluminal approach, mainly
      for pancreatic pseudocyst drainage and full-thickness and mucosal resection of
      various lesions. The approach has never been widely adopted mostly due to
      cumbersome and difficult to maintain methods of gastric access. We propose to
      expand the indications of transgastric laparoscopy by using novel endoscopically
      placed ports to replicate endoscopic procedures particularly in the difficult to
      access proximal stomach such as endoluminal antireflux surgery. Under general
      anesthesia, five female pigs (mean weight: 27.6 kg) had endoscopic placement of
      3, 5 mm intragastric ports (Endo-TAGSS, Leakwood KS, USA) using a technique
      similar to percutaneous endoscopic gastrostomy. A 5-mm laparoscope was used for
      visualization. Laparoendoscopic-assisted plication of the gastroesophageal
      junction (GEJ) was performed using 3-0 interrupted sutures (Polysorb(r),
      Covidien, Mansfield, MA, USA). A functional lumen imagine probe (EndoFLIP(r),
      Crospon, Inc., Galway, Ireland) was used to measure diameter, cross sectional
      area (CSA), distensibility, and compliance of GEJ before and after intervention.
      Once the TAGSS ports were removed, the gastrotomies were closed by using
      endoscopic over-the-scope clips. At the end of the procedure, animals were
      euthanized. Five laparoendoscopic-assisted endoluminal plications were performed.
      The mean operative time was 65.6 min (Endoscopic evaluation: 3.2 min, TAGSS
      Insertion: 11 min, EndoFLIP evaluation + GEJ Plication: 43.25 min, gastric wall
      closure: 15 minutes). In all cases, this technique was effective and allowed to
      achieve an adequate GEJ plication by endoscopic grading and EndoFLIP
      measurements. Median pre-plication GEJ diameter (D) and median pre-plication GEJ
      cross-sectional area (CSA) were 11.42 mm (8.6-13.6 mm) and 104.8 mm2 (58-146
      mm2). After the procedure, these values were decreased to 6.14 mm (5.7-6.6 mm)
      and 29.8 mm2 (25-34 mm2) respectively (p = 0.0079). Median pre-plication
      distensibility (d) and compliance (C) were 7.87 mm2/mmHg (2.4-22.69 mm2/mmHg) and
      190.56 mm3/mmHg (70.9-502.8 mm3/mmHg). After the procedure, these values
      decreased to 1.5 mm2/mmHg (0.7-2.2 mm2/mmHg) and 52.17 mm3/mmHg (21.9-98.7
      mm3/mmHg) respectively (p = 0.0317). No intraoperative events were observed.
      Endoscopically, all valves were felt to be transitioned from a Hill grade 3
      (normal state for the animal model) to a Hill grade 1 at the procedure
      completion. A hybrid laparoendoscopic approach is a feasible alternative for
      performing intragastric procedures with the assistance of conventional
      laparoscopic instruments; especially in cases where the intervention location
      limits the access to standard endoscopy or where endoscopic technology is
      inadequate. Further evaluation is planned in survival models and clinical trials.

PMID- 30295749
TI  - A new method bridging graph theory and residue co-evolutionary networks for
      specificity determinant positions detection.
AB  - Motivation: computational studies of molecular evolution are usually performed
      from a multiple alignment of homologous sequences, on which sequences resulting
      from a common ancestor are aligned so that equivalent residues are placed in the
      same position. Residues frequency patterns of a full alignment or from a subset
      of its sequences can be highly useful for suggesting positions under selection.
      Most methods mapping co-evolving or specificity determinant sites are focused on
      positions, however, they do not consider the case for residues that are
      specificity determinants in one subclass, but variable in others. In addition,
      many methods are impractical for very large alignments, such as those obtained
      from Pfam, or require a priori information of the subclasses to be analyzed.
      Results: in this paper we apply the complex networks theory, widely used to
      analyze co-affiliation systems in the social and ecological contexts, to map
      groups of functional related residues. This methodology was initially evaluated
      in simulated environments and then applied to four different protein families
      datasets, in which several specificity determinant sets and functional motifs
      were successfully detected. Availability: the algorithms and datasets used in the
      development of this project are available on
      http://www.biocomp.icb.ufmg.br/biocomp/software-and-databases/networkstats/.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 30295750
TI  - Estrogen imprinting compromises male sexual behavior and affects the number of
      androgen receptor-expressing hypothalamic neurons.
AB  - Neonatal exposure to high dose 17beta-estradiol (E2) affects the morphology and
      physiology of sex and accessory sex organs in the long term. In this study, we
      examined the effects of E2 imprinting on male sexual behavior, fertility and the
      number of androgen receptor (AR) expressing cells in the hypothalamus. E2-treated
      males showed copulatory behavior represented by mounts and/or intromissions,
      demonstrating the preservation of aspects of male behavior. They had slightly
      increased latency for first intromission and a reduced number of ejaculations,
      associated with a 50% reduction in the fertility index. AR expression in the
      hypothalamus was assessed by RT-PCR, Western blotting and immunohistochemistry.
      Treated rats had a significantly lower ventral prostate weight, demonstrating the
      efficacy of the treatment. The AR mRNA and protein content in the hypothalamus of
      E2-treated animals was reduced to the levels of females. AR-expressing cell
      counts in the ventromedial, anterior medial preoptic, paraventricular nuclei and
      preoptic area were different from control males, and similar to those of females.
      In conclusion, E2 imprinting resulted not only in ill-developed sexual organs,
      but also affected sexual behavior, resulting in a female-type hypothalamus, at
      least with respect to the abundance of AR mRNA and protein and the number of AR
      expressing cells in important regions/tracts.

PMID- 30295751
TI  - Infections of the esophagus: an update on risk factors, diagnosis, and
      management.
AB  - Infectious esophagitis is a leading cause of esophagitis worldwide. While
      esophageal infections have traditionally been associated with immunocompromised
      patients, these disorders are becoming increasingly recognized in immunocompetent
      individuals. The three most common etiologies of infectious esophagitis are
      Candida, herpes simplex virus, and cytomegalovirus. Human papilloma virus
      infection can also involve the esophagus in the form of ulcerative lesions and
      papillomas. Less common etiologies include various other fungal, bacterial, and
      viral organisms. This review provides a comprehensive update on risk factors,
      diagnosis, and management of both common and less common infections of the
      esophagus.

PMID- 30295752
TI  - Texture analysis of computed tomography data using morphologic and metabolic
      delineation of esophageal cancer-relation to tumor type and neoadjuvant therapy
      response.
AB  - The prognostic values of image-based tumor texture analysis based on computed
      tomography (CT) and of limiting the segmented tumor volume to metabolically
      active regions using fludeoxyglucose-positron emission tomography (FDG-PET) were
      studied in 25 patients with esophageal adenocarcinoma and 11 patients with
      squamous cell carcinoma. The aims of this study are to describe their CT-image
      based texture characteristics before and after neoadjuvant therapy and to
      evaluate whether limiting the examined tumor volume to metabolically active
      regions detected with FDG-PET image data would further improve their value.
      Textural parameters (homogeneity, energy, entropy, contrast, and correlation)
      based on gray-level co-occurrence matrices (GLCM) were calculated for 3D volumes
      of segmented esophageal tumors before and after neoadjuvant chemotherapy or
      radiochemotherapy. Histopathological data after surgical resection and textural
      parameters before and after neoadjuvant treatment were compared using the Mann
      Whitney U test. Significant differences in the textural parameters were observed
      between adenocarcinoma and squamous cell carcinoma for homogeneity, energy,
      inertia, and correlation. The use of contrast media during scanning resulted in
      significant differences in homogeneity, energy, entropy, and inertia for
      adenocarcinoma but not squamous cell carcinoma. There was also a significant
      difference in all textural parameters between pathological T status for ypT0-ypT2
      and ypT3-ypT4 adenocarcinomas, but not in squamous cell carcinoma patients. No
      additional value was found from using PET image data to aid segmentation of CT
      images.

PMID- 30295753
TI  - Murine PAIP1 stimulates translation of spermiogenic mRNAs stored by YBX2 via its
      interaction with YBX2.
AB  - The expression of many genes during the post-meiotic stages of spermatogenesis is
      largely regulated by germ cell-specific RNA binding proteins at the level of post
      transcription. One of these RNA binding proteins, YBX2, participates in mRNA
      storage and regulation of translation in haploid spermatids. How YBX2-stored
      mRNAs become translationally competent during spermiogenesis remains unknown. In
      the present study, we report for the first time that YBX2 interacts with PAIP1, a
      protein translation enhancer, in vitro and in vivo. In murine testes, PAIP1 is
      highly expressed and co-localizes with YBX2 in round spermatids. Using sequential
      RNA immunoprecipitation and sequence analysis, we identified a group of
      spermiogenic mRNAs indirectly bound by PAIP1 through YBX2. Translation of mRNAs
      bearing the YBX2 target sequence was significantly blocked by YBX2 protein, but
      was re-initiated when YBX2 was co-expressed with PAIP1 in vitro. Taken together,
      these results indicate that PAIP1 regulates the translation of YBX2-masked mRNAs
      during spermiogenesis, and we propose this YBX2-PAIP1 interaction plays an
      important role in male germ cell development.

PMID- 30295754
TI  - WGS analysis of a penicillin-resistant Neisseria meningitidis strain containing a
      chromosomal ROB-1 beta-lactamase gene.
AB  - Objectives: Neisseria meningitidis is rarely penicillin resistant. We describe
      WGS analysis of a penicillin-resistant N. meningitidis collected from a case of
      invasive meningococcal disease. Methods: Serogrouping, serotyping and
      serosubtyping were performed with specific antibodies. beta-Lactamase was
      detected by nitrocefin. MICs were determined by Etest and agar dilution.
      Sequencing of N. meningitidis genomes was done on the Illumina MiSeq platform and
      genome data were analysed using the Bacterial Isolate Genome Sequence Database
      (BIGSdb) on the PubMLST Neisseria website (https://pubmlst.org/neisseria/).
      Transformation was used to confirm the genetic basis of the penicillin
      resistance. Results: An N. meningitidis blood isolate from a female patient in
      her mid-50s with a painful and septic left shoulder was found to have penicillin
      MIC values of 3-12 mg/L. The isolate was typed as Y: 14, 19: P1.- and ST3587, and
      was weakly beta-lactamase positive. WGS analysis identified a full-length copy of
      the beta-lactamase gene blaROB-1, which was contained on a 1719 bp insert with a
      G + C content of 41.7% (versus a G + C content of N. meningitidis of 51.7%),
      suggesting that the blaROB-1 gene came from a different bacterial species. A
      GenBank analysis of the blaROB-1 gene insert found 99.77% identity with a DNA
      segment found in plasmid pB1000' from Haemophilus influenzae. Transformation of a
      penicillin-susceptible strain with the blaROB-1 gene conferred beta-lactamase
      activity and penicillin resistance. Conclusions: N. meningitidis serogroup Y,
      ST3587 can carry and express the blaROB-1 gene, leading to penicillin resistance.
      It is highly likely that the N. meningitidis isolate acquired the blaROB-1 gene
      from H. influenzae.

PMID- 30295755
TI  - No hearty reception; infusion of CXCL4 impedes tissue repair by macrophages after
      myocardial infarction.

PMID- 30295756
TI  - Single dose of empagliflozin increases in vivo cardiac energy status in diabetic
      db/db mice.

PMID- 30295757
TI  - Contraceptive drugs mitigate experimental stroke-induced brain injury.
AB  - Aims: Effective stroke treatments beyond reperfusion remain scant. The natural
      steroid hormone progesterone has shown protective effects in experimental models
      of brain injury and cardiovascular disease. However, unfavorable bioavailability
      limits its clinical use. Desogestrel and drospirenone are new generation
      progestins with progesterone-like properties, developed as oral contraceptives
      with excellent bioavailability and safety profile. We investigated the
      neuroprotective properties of these progestins in vivo using transient middle
      cerebral artery occlusion (MCAO) and in vitro using an oxygen-glucose deprivation
      and reoxygenation (OGD/R) model in primary neuronal cells. Methods and Results:
      MCAO was induced in female, female ovariectomized (modeling postmenopausal
      females) and male mice. Treatment with the progestins resulted in less severe
      strokes after MCAO and less neuronal death in OGD/R. Desogestrel and drospirenone
      induced higher expression levels of GABAAR alpha4 and delta subunits within the
      brain, suggesting changes in GABAAR configuration favoring tonic inhibition as
      potential mechanism of action. Treatment with the GABAAR blocker picrotoxin
      abolished the protection afforded by the progestins in vivo and in vitro.
      Conclusions: For the first time, here we delineate a potential role of
      desogestrel and drospirenone, both clinically approved and safe drugs in
      mitigating the consequences of stroke. Contraception with desogestrel and
      drospirenone in progestin-only preparations may be particularly beneficial for
      women at risk of stroke.

PMID- 30295758
TI  - 2-arachidonoylglycerol mobilizes myeloid cells and worsens heart function after
      acute myocardial infarction.
AB  - Aims: Myocardial infarction leads to an enhanced release of endocannabinoids and
      a massive accumulation of neutrophils and monocytes within the ischemic
      myocardium. These myeloid cells originate from hematopoietic precursors in the
      bone marrow and are rapidly mobilized in response to myocardial infarction. We
      aimed to determine whether endocannabinoid signaling is involved in myeloid cell
      mobilization and cardiac recruitment after ischemia onset. Methods and results:
      Intravenous administration of endocannabinoid 2-arachidonoylglycerol into
      wildtype C57BL6 mice induced a rapid increase of blood neutrophil and monocyte
      counts as measured by flow cytometry. This effect was blunted when using
      cannabinoid receptor 2 knockout mice. In response to myocardial infarction
      induced in wildtype mice, the lipidomic analysis revealed significantly elevated
      plasma and cardiac levels of the endocannabinoid 2-arachidonoylglycerol 24 h
      after infarction, but no changes in anandamide, palmitoylethanolamide and
      oleoylethanolamide. This was a consequence of an increased expression of 2
      arachidonoylglycerol synthesizing enzyme diacylglycerol lipase and a decrease of
      metabolizing enzyme monoacylglycerol lipase in infarcted hearts, as determined by
      quantitative RT-PCR analysis. The opposite mRNA expression pattern was observed
      in bone marrow. Pharmacological blockade of monoacylglycerol lipase with JZL184
      and thus increased systemic 2-arachidonoylglycerol levels in wildtype mice
      subjected to myocardial infarction resulted in elevated cardiac CXCL1, CXCL2 and
      MMP9 protein levels as well as higher cardiac neutrophil and monocyte counts 24 h
      after infarction compared to vehicle-treated mice. Increased post-myocardial
      infarction inflammation in these mice led to an increased infarct size, an
      impaired ventricular scar formation assessed by histology and a worsened cardiac
      function in echocardiography evaluations up to 21 days. Likewise, JZL184
      administration in a myocardial ischemia-reperfusion model increased cardiac
      myeloid cell recruitment and resulted in a larger fibrotic scar size.
      Conclusions: These findings suggest that changes in endocannabinoid gradients due
      to altered tissue levels contribute to myeloid cell recruitment from the bone
      marrow to the infarcted heart, with crucial consequences on cardiac healing and
      function.

PMID- 30295759
TI  - Death of an antioxidant brings heart failure with preserved ejection fraction to
      life: 5-oxoproline and post-ischaemic cardio-renal dysfunction.

PMID- 30295760
TI  - Cost-effectiveness of 3 months of weekly rifapentine and isoniazid compared with
      other standard treatment regimens for latent tuberculosis infection: a decision
      analysis study.
AB  - Background: Latent tuberculosis infection (LTBI) is a critical driver of the
      global burden of active TB, and therefore LTBI treatment is key for TB
      elimination. Treatment regimens for LTBI include self-administered daily
      isoniazid for 6 (6H) or 9 (9H) months, self-administered daily rifampicin plus
      isoniazid for 3 months (3RH), self-administered daily rifampicin for 4 months
      (4R) and weekly rifapentine plus isoniazid for 3 months self-administered (3HP
      SAT) or administered by a healthcare worker as directly observed therapy (3HP
      DOT). Data on the relative cost-effectiveness of these regimens are needed to
      assist policymakers and clinicians in selecting an LTBI regimen. Objectives: To
      evaluate the cost-effectiveness of all regimens for treating LTBI. Methods: We
      developed a Markov model to investigate the cost-effectiveness of 3HP-DOT, 3HP
      SAT, 4R, 3RH, 9H and 6H for LTBI treatment in a cohort of 10 000 adults with
      LTBI. Cost-effectiveness was evaluated from a health system perspective over a 20
      year time horizon. Results: Compared with no preventive treatment, 3HP-DOT, 3HP
      SAT, 4R, 3RH, 9H and 6H prevented 496, 470, 442, 418, 370 and 276 additional
      cases of active TB per 10 000 patients, respectively. All regimens reduced costs
      and increased QALYs compared with no preventive treatment. 3HP was more cost
      effective under DOT than under SAT at a cost of US$27 948 per QALY gained.
      Conclusions: Three months of weekly rifapentine plus isoniazid is more cost
      effective than other regimens. Greater recognition of the benefits of short
      course regimens can contribute to the scale-up of prevention and achieving the
      'End TB' targets.

PMID- 30295761
TI  - Nocturnal noise knocks NOS by Nox: mechanisms underlying cardiovascular
      dysfunction in response to noise pollution.

PMID- 30295762
TI  - Managing the Patient with Heart Failure in the Emergency Department.

PMID- 30295763
TI  - The K-index and the hubs of science.

PMID- 30295764
TI  - Young Cardiologist Researchers in Kemerovo.

PMID- 30295766
TI  - Inflammation: the new cardiovascular risk factor.

PMID- 30295765
TI  - The Role of the European Society of Cardiology in improving the quality of
      cardiac care at the level of national cardiac societies.

PMID- 30295768
TI  - Jeroen Bax visits to St Petersburg, Russia.

PMID- 30295767
TI  - The Heart Failure Unit At Shaare Zedek Hospital Medical Center.

PMID- 30295770
TI  - Predicting individual physiologically acceptable states at discharge from a
      pediatric intensive care unit.
AB  - Objective: Quantify physiologically acceptable PICU-discharge vital signs and
      develop machine learning models to predict these values for individual patients
      throughout their PICU episode. Methods: EMR data from 7256 survivor PICU episodes
      (5632 patients) collected between 2009 and 2017 at Children's Hospital Los
      Angeles was analyzed. Each episode contained 375 variables representing
      physiology, labs, interventions, and drugs. Between medical and physical
      discharge, when clinicians determined the patient was ready for ICU discharge,
      they were assumed to be in a physiologically acceptable state space (PASS) for
      discharge. Each patient's heart rate, systolic blood pressure, diastolic blood
      pressure in the PASS window were measured and compared to age-normal values,
      regression-quantified PASS predictions, and recurrent neural network (RNN) PASS
      predictions made 12 hours after PICU admission. Results: Mean absolute errors
      (MAEs) between individual PASS values and age-normal values (HR: 21.0 bpm; SBP:
      10.8 mm Hg; DBP: 10.6 mm Hg) were greater (p < .05) than regression prediction
      MAEs (HR: 15.4 bpm; SBP: 9.9 mm Hg; DBP: 8.6 mm Hg). The RNN models best
      approximated individual PASS values (HR: 12.3 bpm; SBP: 7.6 mm Hg; DBP: 7.0 mm
      Hg). Conclusions: The RNN model predictions better approximate patient-specific
      PASS values than regression and age-normal values.

PMID- 30295769
TI  - Trends in antifungal use in US hospitals, 2006-12.
AB  - Background: Although trends in antibiotic use have been characterized, less is
      known about antifungal use. Data on antifungal use are important for
      understanding practice patterns, assessing emergence of antifungal resistance and
      developing antifungal stewardship programmes. We estimated national trends in
      inpatient antifungal use in the USA. Methods: Using billing data for antifungals
      from the Truven Health MarketScan(r) Hospital Drug Database during 2006-12, we
      estimated the proportion of discharges at which antifungals were given and days
      of therapy (DOT)/1000 patient days (PDs) by antifungal drug type, year, patient
      and facility characteristics. We created national estimates using weights
      generated from Centers for Medicare and Medicaid Services data and assessed
      trends over time. Results: Overall, 2.7% of all inpatients and 7.7% of those in
      ICUs received antifungals. The estimated DOT/1000 PDs for any antifungal was 35.0
      for all inpatients and 73.7 for ICU patients. Azoles accounted for 80% of all
      antifungal use (28.5/1000 PDs), followed by echinocandins (5.0/1000 PDs). By
      multivariable trend analysis, DOT/1000 PDs for azoles (-21%) and polyenes (-47%)
      decreased between 2006 and 2012, whereas echinocandins increased 11% during 2006
      10 and declined after 2011. Unspecified septicaemia, HIV and antineoplastic
      therapy were among the top primary diagnosis codes for patients who received
      antifungals. Conclusions: Antifungals were most frequently used in ICU settings
      and fluconazole accounted for a large, but declining, proportion of antifungal
      use. Antifungal stewardship efforts may have the most impact if focused in ICUs,
      among certain patient groups (e.g. HIV and malignancy) and on stopping empirical
      antifungal therapy for unspecified sepsis when not indicated.

PMID- 30295771
TI  - Antimicrobial resistance and virulence factors of Klebsiella pneumoniae affecting
      30 day mortality in patients with bloodstream infection.
AB  - Objectives: To investigate the risk factors of patients with Klebsiella
      pneumoniae (KP) bloodstream infection (BSI) with a focus on antimicrobial
      resistance and virulence factors. Methods: All KP BSI patients (n = 579) from six
      general hospitals during a 1 year period were included in this study. The risk
      factors of hosts and causative KP isolates were assessed to determine
      associations with the 30 day mortality of KP BSI patients by multivariate Cox
      hazards modelling. Results: The 30 day mortality rate of KP BSI patients was
      16.9% (98/579). Among the host-associated factors, increased SOFA score and
      leucopenia status exhibited strong associations with increased 30 day mortality.
      Among the pathogenic factors, carriage of the pks gene cluster (adjusted HR 1.80;
      95% CI 1.16-2.79) was a risk factor, especially when accompanied by MDR. In this
      regard, KP isolates of the wzi50 capsular type (n = 22) frequently harboured pks
      (63.6%, 14/22) and ybtA (68.2%, n = 15) and mostly exhibited MDR (63.6%, n = 14),
      resulting in increased 30 day mortality. In contrast, hypermucoviscous KP
      isolates showed an inverse association with 30 day mortality (adjusted HR 0.55;
      95% CI 0.33-0.90). Conclusions: Despite the reported virulence of
      hypermucoviscous KP strains, they were associated with good prognoses in KP BSI
      patients. Importantly, carriage of the pks gene cluster, which is responsible for
      the synthesis of colibactin, was a relevant marker of early mortality.

PMID- 30295772
TI  - Intraoperative computed tomography-guided pulmonary tumour localization: a
      thoracic surgeon's learning curve.
AB  - OBJECTIVES: With the increasing availability of hybrid operating rooms, single
      stage tumour localization and removal under intraoperative computed tomography
      (CT) guidance is gaining popularity. The objective of this study was to describe
      the learning curve for this procedure. METHODS: Over a 15-month period, a single
      team of thoracic surgeons without experience in intraoperative CT-guided lung
      tumour localization performed a total of 91 procedures in 89 patients. All these
      procedures were conducted in a hybrid operating room equipped with cone-beam CT
      and a laser navigation system. The learning curve was analysed using the
      cumulative sum method (target success rate 90%), whereas the moving average was
      used as an indicator of localization time. RESULTS: The mean lung tumour size on
      preoperative CT images was 7.81 mm, whereas their mean distance from the pleural
      surface was 10.16 mm. The localization time (mean 21.19 min) was inversely
      associated with the surgeon's experience (Pearson's r = -0.6601; P < 0.001). The
      moving average analysis revealed that localization time stabilized after 32
      procedures. There were 6 failures; of these, 2 occurred during lesion
      localization (as a result of needle puncture-related pneumothorax) and 4 during
      surgery (caused either by wire dislodgement or dye spillage). The cumulative sum
      analysis revealed that proficiency was achieved after 38 procedures. The mean
      localization time and success rates before and after procedure 38 were 32.13 min
      vs 13.34 min (P < 0.001) and 86.8% vs 98.1% (P = 0.078), respectively.
      CONCLUSIONS: The procedural time and success rates of intraoperative CT-guided
      lung tumour localization were optimized after 38 consecutive procedures.

PMID- 30295773
TI  - Corrigendum to 'Left ventricular function can be continuously monitored with an
      epicardially attached accelerometer sensor' [Eur J Cardiothorac Surg 2014;46:313
      20].

PMID- 30295774
TI  - Alterations in transmembrane pressures during continuous venovenous
      haemofiltration significantly contribute to the pharmacokinetic variability of
      meropenem: a case series of three patients.

PMID- 30295775
TI  - Zoonotic Malaria: The Better You Look, the More You Find.

PMID- 30295776
TI  - Larviciding Culex spp. (Diptera: Culicidae) Populations in Catch Basins and Its
      Impact on West Nile Virus Transmission in Urban Parks in Atlanta, GA.
AB  - In urban environments, road-side catch basins are common larval habitats of Culex
      spp. (Diptera: Culicidae) mosquitoes and important targets of larval control in
      areas subject to West Nile virus (WNv) transmission. We quantified the impact of
      larviciding basins on Culex spp. populations and WNv infection prevalence by
      treating basins in and around urban parks in Atlanta, GA, using Mosquito Dunks
      and Bits (active ingredient, a.i., Bacillus thuringiensis subsp. isrealensis,
      Dunks-10.31%, Bits-2.86%) and Altosid 30-Day Briquets (a.i., S-methoprene 8.62%)
      in two separate seasons. Treatments were coupled with WNv surveillance using
      gravid traps and aspiration of adults resting in basins. Larviciding led to >90%
      reductions in Culex spp. larval and pupal collections (Dunks/Bits) and >90% pupal
      mortality (Briquets) in treated sites during treatment periods; however, we did
      not observe significant reductions in Culex spp. collections in gravid traps
      (general linear mixed-effects model [GLMM] result, P > 0.1) or in adults
      collected resting in basins (GLMM, P > 0.5). In addition, WNv infection
      prevalence in Culex spp. mosquitoes was similar between treated and untreated
      sites (GLMM, P > 0.05). Larval control remains important for controlling WNv in
      Atlanta; however, at the scale and frequency applied in our study, larval control
      alone may not lead to meaningful reductions in adult populations and WNv
      infection prevalence. A greater understanding of the annual dynamics of Culex
      spp. breeding and the importance of basins as Culex spp. larval habitats are
      needed to meaningfully affect WNv in cities such as Atlanta.

PMID- 30295777
TI  - Sellar Region Atypical Teratoid/Rhabdoid Tumors in Adults: Clinicopathological
      Characterization of Five Cases and Review of the Literature.
AB  - Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant CNS neoplasms
      that typically occur in children <2 years of age. These are characterized by high
      grade histologic features and mutations of the INI1/SMARCB1 gene readily detected
      by loss of expression by immunohistochemistry. Among adults, the majority of
      AT/RTs occurs in the cerebral hemispheres. A small number of adult AT/RTs
      involving the sellar and suprasellar region reported in the literature suggest a
      distinct clinical course for this group. Here, we describe detailed clinical and
      genetic characterization of 5 adult patients with AT/RTs involving the sellar and
      suprasellar region, and provide a review of the available clinical and genetic
      features of 22 previously reported cases in order to help increase our
      understanding of this unusual entity.

PMID- 30295778
TI  - The retrospective study of 93 patients with transmigration of mandibular canine
      and a comparative analysis with a control group.
AB  - Objectives: The aim of this study was to evaluate characteristics of patients
      with unilateral transmigration of a mandibular canine in the largest study group
      presented until now. Materials and methods: The study group consisted of 93
      patients with unilateral transmigration of mandibular canine; the control group
      included 85 non-affected patients. Type of transmigration, status of deciduous
      and permanent canines, prevalence of missing teeth, class of occlusion, and space
      conditions were assessed to draw comparisons between groups. Results: In this
      study, 64.5 per cent patients presented type 1 of transmigration; types 2, 3, 4,
      and 5 were present in, respectively, 23.7, 5.4, 4.3, and 2.1 per cent patients.
      There was a clear, statistically significant difference (P < 0.0001) between the
      mean crown and apex migration and angulation for the three groups of canines
      (transmigrated, contralateral, and control), whereas no differences were observed
      for the total number of permanent teeth present. In the study group, 73.1 per
      cent patients retained their primary canine on the affected side and 18.3 per
      cent on the contralateral side; in the control group, 22.3 per cent subjects had
      at least one primary canine. There was a statistically significant difference in
      the distribution of types of malocclusion between the study and the control
      groups. Conclusions: Transmigration of mandibular canine was associated with the
      presence of retained primary canine on the affected side, higher mesial tilting
      of contralateral mandibular canine when compared to the canines in the control
      group. Additionally, higher prevalence of Angle's Class I occlusion in patients
      with canine transmigration was recorded.

PMID- 30295779
TI  - Colitis alters oxysterol metabolism and is affected by 4beta-hydroxycholesterol
      administration.
AB  - Background and aims: Inflammatory bowel diseases (IBD) represent a challenging
      health issue with a complex etiology implicating genetic and environmental
      parameters. Although the understanding of their pathophysiology has improved,
      much remains to be explored. In this context, bioactive lipids, more specifically
      oxysterols, i.e. oxygenated derivatives of cholesterol, represent an interesting
      avenue to investigate. Indeed, oxysterols or their receptors are involved in
      inflammation and immune regulation. Therefore, we set out to study the oxysterome
      in IBD. Methods: We used both HPLC-MS and molecular biology tools to quantify
      oxysterol levels and the expression of their metabolic enzymes in several models
      of murine colitis (both acute and chronic), as well as in colon biopsies from
      patients with Crohn's disease and ulcerative colitis. Results: We found that the
      oxysterome is altered in IBD, both in acute and chronic murine models as well as
      in human IBD. Two of the oxysterols quantified, 4beta-hydroxycholesterol and 25
      hydroxycholesterol, were consistently altered in all of our models and therefore
      could be of interest in this context. Hence, we administered them to mice with
      colitis. While 25-hydroxycholesterol had no effect, 4beta-hydroxycholesterol
      worsened colon inflammation. Conclusions: Our study addresses the potential
      involvement of oxysterols in colitis and clearly points towards an active role as
      well as a clinical relevance for these bioactive lipids.

PMID- 30295780
TI  - Empirical treatment of urinary tract infections: how rational are our guidelines?
AB  - Objectives: This study considers susceptibility test results obtained over a 6
      month period for Enterobacteriaceae that caused urinary tract infections (UTIs)
      in the Cork region of Ireland and uses these results to examine the suitability
      of Irish empirical treatment guidelines. Patients and methods: UTI-causing
      Enterobacteriaceae isolates were analysed using EUCAST guidelines to determine
      resistance to a set of commonly prescribed antimicrobial agents, i.e. ampicillin,
      amoxicillin/clavulanate, cefalexin, ciprofloxacin, nitrofurantoin and
      trimethoprim. Patients were categorized by age and patient type, based on origin
      (hospital inpatients, patients in long-term care facilities and all other non
      hospitalized patients). In total, 8999 test results were analysed using the IBM
      Cognos Analytics Series 7 interrogation tool and Microsoft Office Excel. Results:
      A variety of resistance patterns were observed. Only one antimicrobial agent,
      nitrofurantoin, demonstrated a resistance rate of less than 20% for all patient
      categories considered. Conclusions: Previous studies determined that a resistance
      rate of >20% renders an antimicrobial agent unsuitable for use as an empirical
      treatment option. This study demonstrated that this resistance rate is exceeded
      in many cases, potentially rendering some antimicrobial agents unsuitable for use
      as empirical treatment. We suggest that the focus on susceptibility when
      producing surveillance data to create empirical treatment guidelines may
      inadvertently camouflage resistance rates. The findings of this study highlight
      the need for laboratory-guided treatment of UTIs and ideally a pre-emptive sample
      should be obtained for laboratory investigation prior to commencement of
      antimicrobial therapy.

PMID- 30295781
TI  - Biomarkers Are Associated With Clinical and Endoscopic Outcomes With Vedolizumab
      Treatment in Ulcerative Colitis.
AB  - Background: Vedolizumab inhibits alpha4beta7-mediated lymphocyte trafficking and
      is effective in ulcerative colitis (UC). This study evaluated drug and biomarker
      concentrations and patient outcomes during vedolizumab treatment in UC. Methods:
      Prospectively scored maintenance clinical (26.5 weeks; interquartile range [IQR],
      16.3-37.0 weeks) and endoscopic (23.5 weeks; IQR, 16.8-35.6 weeks) outcomes were
      compared with serum vedolizumab concentrations, antivedolizumab antibodies, and
      serum biomarkers at baseline and weeks 2, 6, 14, and 26. A linear mixed-effects
      model compared biomarker trajectories over time between clinical and endoscopic
      remitters and nonremitters. Results: Thirty-two patients were included. Soluble
      (s)-tumor necrosis factor (TNF)-alpha, s-alpha4beta7, s-mucosal addressin cell
      adhesion molecule (s-MAdCAM-1), and s-amyloid A (s-AA) significantly changed with
      treatment. A linear mixed-effects model demonstrated that s-alpha4beta7 (P =
      0.044) increased and s-MAdCAM-1 (P = 0.006) and s-vascular cell adhesion molecule
      1 (s-VCAM-1, P = 0.001) decreased more rapidly in patients achieving clinical
      remission in maintenance. S-MAdCAM-1 (P = 0.005), s-intracellular adhesion
      molecule-1 (ICAM-1; P = 0.014), s-VCAM-1 (P < 0.001), and s-TNF (P = 0.052)
      decreased more rapidly in endoscopic remitters. In clinical remitters, higher
      week 14 (20.3 ng/mL vs 6.0 ng/mL; P = 0.013) and week 26 (14.1 ng/mL vs 8.6
      ng/mL; P = 0.05) s-alpha4beta7 were observed. In endoscopic remitters, week 2
      (6.7 pg/mL vs 17.8 pg/mL; P = 0.038) and week 6 (3.9 pg/mL vs 15.6 pg/mL; P =
      0.005) s-TNF and week 14 s-VCAM (589.1 ng/mL vs 746.0 ng/mL; P = 0.05) were
      lower. Conclusion: Serum biomarkers were associated with outcomes in vedolizumab
      treated UC patients. s-alpha4beta7 increased, whereas s-MAdCAM-1, s-VCAM-1, s
      ICAM-1, and s-TNF decreased more rapidly in remitters. At individual time points,
      induction s-TNF and maintenance s-VCAM-1 concentrations were lower, whereas
      maintenance s-alpha4beta7 concentrations were higher in remitters.

PMID- 30295782
TI  - Effect of Temperature on Oviposition Behavior and Egg Load of Blow Flies
      (Diptera: Calliphoridae).
AB  - Making optimal oviposition decisions is especially important for female carrion
      colonizing insects whose larvae often depend on ephemeral resources. Optimal
      oviposition theory predicts that females should exhibit behaviors that will
      maximize the performance of their offspring. Oviposition can be influenced by a
      variety of factors, including temperature. The aim of this study was to
      investigate the effects of temperature on the oviposition behavior and egg load
      of two blow fly species native to southern Ontario: Phormia regina Meigen, and
      Lucilia sericata Meigen (Diptera: Calliphoridae). Using fetal pig carcasses as an
      oviposition substrate, we assessed the length of time until the first oviposition
      event, preferred oviposition sites, and the total number of eggs oviposited. For
      each of the two species, five different temperature treatments ranging from 15 to
      35 degrees C were used. Temperature influenced time to the first oviposition
      event, as well as the number of eggs deposited by L. sericata and P. regina. As
      temperature increased, oviposition occurred faster with more eggs deposited for
      these two species. Female P. regina, in particular, demonstrated a higher egg
      load with increasing temperature. Differences in optimal temperatures for
      reproduction, including egg load and oviposition, may be a mechanism driving
      seasonal temporal resource partitioning leading to species coexistence utilizing
      ephemeral resources.

PMID- 30295783
TI  - Impact of socioeconomic status on incident heart failure and left ventricular
      dysfunction: Systematic review and meta-analysis.
AB  - Aims: Socioeconomic status (SES) is recognizably linked with incident heart
      failure (HF) risk and the association of SES with geography presents a potential
      target for geographical location of preventive health services. To better inform
      policy we sought to quantify the independent association between SES and incident
      HF and investigate differences by type of SES measure. Methods and results:
      MEDLINE and EMBASE were searched up to August 2018. Observational studies and
      randomized trials reporting adjusted HF incidence by stratified socioeconomic
      measures were included. Effect sizes reflected HF incidence in the lowest versus
      highest SES stratum and were pooled using a random-effects model. Low SES
      referred to the lowest resource stratum, the definition of which varied across
      studies: meta-analysis was only performed where strata were comparable.
      Statistical heterogeneity was assessed using the I2 statistic. Eleven studies
      comprising 6,308,006 individuals and 104,217 HF events found that low SES was
      associated with an increase in risk of incident HF ranging between 43% and 87%
      depending on SES measure, with an overall estimate of 62% (hazard ratio [HR]
      1.62, 95% CI 1.50-1.76). By individual measure, HRs of 1.66 (95% CI 1.3-2.11),
      1.87 (95% CI 1.33-2.62) and 1.54 (95% CI 1.22-1.95) were observed for education,
      income and occupation respectively. For area-level indexes, HRs were 1.43 (95% CI
      1.2-1.69) (Carstairs index) and 1.61 (95% CI 1.56-1.65) (index of multiple
      deprivation). Conclusion: Low SES assessed by all common measures confers
      independent risk for incident HF. These findings carry implications for the
      design and delivery of HF prevention programs.

PMID- 30295784
TI  - Ustekinumab Is Effective for the Treatment of Crohn's Disease of the Pouch in a
      Multicenter Cohort.
AB  - Background: Crohn's disease (CD) of the pouch and chronic pouchitis occur in
      approximately 10% of patients after ileal pouch-anal anastomosis (IPAA) for
      refractory ulcerative colitis (UC) or UC-related dysplasia. The efficacy of anti
      tumor necrosis factor (anti-TNF) agents and vedolizumab have been reported for
      the treatment of CD of the pouch and chronic pouchitis, but little is known
      regarding the use of ustekinumab in these settings. Our primary aim was to
      evaluate the efficacy of ustekinumab for these conditions. Methods: This is a
      retrospective, multicenter cohort study evaluating the efficacy of ustekinumab in
      patients with CD of the pouch and chronic pouchitis. Clinical response or
      remission was judged by the treating physician's assessment at 6 months. Results:
      Fifty-six patients (47 with CD of the pouch and 9 with chronic pouchitis) were
      included the study. Of these, 73% had previously been treated with either anti
      TNF therapy, vedolizumab, or both after IPAA. Among patients with CD of the pouch
      and chronic pouchitis, 83% demonstrated clinical response 6 months after
      induction with ustekinumab. Responders demonstrated significantly less pouch
      inflammation on endoscopy when compared with nonresponders (29% vs 100%; P =
      0.023). Higher mean body mass index at induction (26.3 vs 23.7; P = 0.033) and
      male sex (83% vs 30%; P = 0.014) were significant predictors of nonresponse to
      ustekinumab in those with CD of the pouch. Conclusion: In this refractory patient
      population, ustekinumab appears to be a safe and effective treatment for chronic
      pouchitis and CD of the pouch in biologic-naive patients and those with prior
      anti-TNF or vedolizumab therapy failure.
      10.1093/ibd/izx005_video1izy302.video15844889626001.

PMID- 30295786
TI  - A Systematic Review of Self-Management Interventions for Children and Adolescents
      With Inflammatory Bowel Disease.
AB  - Background: Self-management of inflammatory bowel disease is complex. Children
      and adolescents (CA) with inflammatory bowel disease (IBD) often have difficulty
      with managing aspects of their condition, resulting in treatment nonadherence and
      impaired psychosocial function. Self-management interventions are developed to
      help support patients and their parents/carers to effectively self-manage. The
      aim of this systematic review was to evaluate the efficacy of self-management
      interventions in children and adolescents with IBD. Methods: The review was
      conducted in accordance with Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses guidelines. A systematic literature search of the following
      databases was conducted to identify controlled trials of interventions aiming to
      enhance IBD self-management in CA: Medline, Embase, Cochrane, CINAHL, and
      PsychINFO. Two reviewers screened articles for inclusion. Results: Nine trials
      (11 articles) met the inclusion criteria. Most were underpowered, with 7
      recruiting fewer than 50 participants. The interventions aimed to enhance
      psychological well-being (n = 5), medication adherence (n = 3), or calcium intake
      (n = 1). There was considerable heterogeneity in intervention content and
      outcomes assessment. Some benefits were reported in disease activity, adherence,
      and psychological well-being, but findings were inconsistent. Conclusions: Self
      management is difficult for CA with IBD; however, this review identified only a
      small number of interventions to support self-management, most of which were
      underpowered and only 1 that was conducted outside the United States. Clinical
      consensus is required on which self-management activities should be recommended
      to patients and targeted in interventions and which core outcomes should be
      assessed. Adequately powered trials of interventions are required to identify how
      best to support self-management in CA with IBD.

PMID- 30295785
TI  - A propensity score-matched comparison of infliximab and adalimumab in TNF-alpha
      inhibitors naive and non-naive patients with Crohn's disease: real-life data from
      the Sicilian Network for Inflammatory Bowel Disease (SN-IBD).
AB  - Background and Aims: There is an unmet need to better understand the
      effectiveness of different biologics in inflammatory bowel diseases. We aimed at
      performing a multicenter, real-life comparison of the effectiveness of infliximab
      (IFX) and adalimumab (ADA) in Crohn's disease (CD). Methods: Data of consecutive
      patients with CD treated with IFX and ADA from January 2013 to May 2017 were
      extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease.
      We used a propensity score matching accounting for the main baseline
      characteristics in TNF-alpha inhibitor naive and non-naive patients. Results: 632
      patients (735 total treatments) were included. Among naive patients, a clinical
      benefit (the sum of steroid-free remission plus clinical response) was achieved
      in 81.8% patients treated with ADA and in 77.6% patients treated with IFX
      (adjusted OR: 1.23, 95%CI 0.63-2-44, p=0.547) at 12 weeks; after one year, a
      clinical benefit was achieved in 69.2% of patients treated with ADA and in 64.5%
      patients treated with IFX (adjusted OR: 1.10, 95%CI 0.61-1.96, p=0.766). Among
      non-naive patients, a clinical benefit was achieved in 61.7% of patients treated
      with ADA and in 68.1% of patients treated with IFX (adjusted OR: 0.72, 95%CI 0.21
      2.44, p=0.600) at 12 weeks; after one year, a clinical benefit was achieved in
      48.9% of patients treated with ADA and in 40.4% patients treated with IFX
      (adjusted OR: 1.23, 95%CI 0.54-2.86, p=0.620). Conclusions: In this propensity
      score-matched comparison of ADA and IFX in CD, both drugs showed high rates of
      clinical benefit, without significant differences between them.

PMID- 30295787
TI  - Structured Illumination Approaches for Super-Resolution in Plant Cells.
AB  - The advent of super-resolution techniques in biological microscopy has opened new
      frontiers for exploring the molecular distribution of proteins and small
      molecules in cells. Improvements in optical design and innovations in the
      approaches for the collection of fluorescence emission have produced substantial
      gains in signal from chemical labels and fluorescent proteins. Structuring the
      illumination to elicit fluorescence from specific or even random patterns allows
      the extraction of higher order spatial frequencies from specimens labeled with
      conventional probes. Application of this approach to plant systems for super
      resolution imaging has been relatively slow owing in large part to aberrations
      incurred when imaging through the plant cell wall. In this brief review, we
      address the use of two prominent methods for generating super-resolution images
      in living plant specimens and discuss future directions for gaining better access
      to these techniques.

PMID- 30295788
TI  - Beware of early drug intolerance in secondary prevention of cardiovascular
      disease.

PMID- 30295791
TI  - Systemic right ventricular takotsubo cardiomyopathy.

PMID- 30295789
TI  - Adult-Onset Hepatocyte GH Resistance Promotes NASH in Male Mice, Without Severe
      Systemic Metabolic Dysfunction.
AB  - Nonalcoholic fatty liver disease (NAFLD), which includes nonalcoholic
      steatohepatitis (NASH), is associated with reduced GH input/signaling, and GH
      therapy is effective in the reduction/resolution of NAFLD/NASH in selected
      patient populations. Our laboratory has focused on isolating the direct vs
      indirect effects of GH in preventing NAFLD/NASH. We reported that chow-fed, adult
      onset, hepatocyte-specific, GH receptor knockdown (aHepGHRkd) mice rapidly
      (within 7 days) develop steatosis associated with increased hepatic de novo
      lipogenesis (DNL), independent of changes in systemic metabolic function. In this
      study, we report that 6 months after induction of aHepGHRkd early signs of NASH
      develop, which include hepatocyte ballooning, inflammation, signs of mild
      fibrosis, and elevated plasma alanine aminotransferase. These changes occur in
      the presence of enhanced systemic lipid utilization, without evidence of white
      adipose tissue lipolysis, indicating that the liver injury that develops after
      aHepGHRkd is due to hepatocyte-specific loss of GH signaling and not due to
      secondary defects in systemic metabolic function. Specifically, enhanced hepatic
      DNL is sustained with age in aHepGHRkd mice, associated with increased hepatic
      markers of lipid uptake/re-esterification. Because hepatic DNL is a hallmark of
      NAFLD/NASH, these studies suggest that enhancing hepatocyte GH signaling could
      represent an effective therapeutic target to reduce DNL and treat NASH.

PMID- 30295790
TI  - Association of the Dundee severity classification with mortality, length of stay
      and readmission in adult inpatients with cellulitis.
AB  - Background: The Dundee classification is a simple severity assessment tool that
      could optimize treatment decisions and clinical outcomes in adult patients with
      cellulitis; however, it has not been validated in a large cohort. Objectives: To
      determine whether the Dundee classification reliably identified those patients
      with cellulitis who had a higher mortality, a longer length of hospital stay or
      an increased risk of readmission. Methods: We performed a retrospective study of
      all adults with a primary discharge diagnosis of cellulitis admitted to Auckland
      City Hospital from August 2013 to June 2015. We classified patients by severity
      using the Dundee scoring system. Results: The 30 day all-cause mortality in adult
      patients with a discharge diagnosis of cellulitis was 2% (29/1462) overall, and
      was 1% (10/806), 2% (6/271), 3% (10/353) and 9% (3/32) in Classes 1, 2, 3 and 4
      of the Dundee classification, respectively (P = 0.01). Mortality was strongly
      associated with age >65 years (OR 9.37, 95% CI 3.00-41.23) and with heart failure
      (OR 6.16, 95% CI 2.73-14.23). There were significant associations between the
      Dundee classification and the incidence of bacteraemia, the length of hospital
      stay and the rate of readmission to hospital. Conclusions: The Dundee
      classification is a simple, reliable tool that can be easily applied in clinical
      settings to predict risk of mortality in order to determine which patients can be
      managed in the community with oral or intravenous therapy, and which require
      inpatient care.

PMID- 30295792
TI  - RCPAQAP audit of antimicrobial reporting in Australian and New Zealand
      laboratories: opportunities for laboratory contribution to antimicrobial
      stewardship.
AB  - Objectives: A 2017 laboratory survey conducted by the Royal College of
      Pathologists of Australasia Quality Assurance Programs (RCPAQAP) asked
      participants which antimicrobials they would report for given organisms in either
      blood or urine cultures in order to identify opportunities for improvement of
      antimicrobial reporting. Methods: Over-reporting was defined as reporting of
      broad-spectrum antimicrobials on isolates susceptible to narrow-spectrum
      antimicrobials. Inappropriate reporting was defined as reporting antimicrobials
      not appropriate for the site of infection. Results: For a fully susceptible
      Escherichia coli in blood culture, 65% of laboratories (55/84) over-reported at
      least one antimicrobial. Importantly, 15% (10/65) of laboratories that tested
      meropenem reported the result. A significant proportion of laboratories (12%,
      10/84) reported antimicrobials generally considered inappropriate for treatment
      of bacteraemia on blood culture isolates. Overall, 82% (77/94) of laboratories
      either over-reported or inappropriately reported at least one antimicrobial.
      Conclusions: This survey identifies significant opportunities for improvement and
      standardization of 'cascade' or 'selective' reporting of antimicrobials and
      highlights ways in which microbiology laboratories can contribute to
      antimicrobial stewardship and judicious use of antimicrobials.

PMID- 30295793
TI  - NLRP3 Inflammasome-Related Proteins Are Upregulated in the Putamen of Patients
      With Multiple System Atrophy.
AB  - Multiple system atrophy (MSA) is a neurodegenerative disease characterized by
      parkinsonism, ataxia, and autonomic dysfunction. Microglial infiltration is an
      important mediator in MSA. The nucleotide-binding domain, leucine-rich repeats
      containing family, pyrin domain-containing-3 (NLRP3) inflammasome complex,
      comprising NLRP3, apoptotic speck protein containing a caspase recruitment domain
      (ASC), and cysteine aspartic acid protease 1 (Caspase 1), regulates microglial
      inflammation in several neurodegenerative diseases. However, its role in MSA
      remains unknown. This study aimed to investigate the role of the NLRP3
      inflammasome in MSA. Immunohistochemical staining of postmortem brains from 11
      cases of MSA, 5 of Parkinson disease, and 6 age-matched controls were assessed.
      The relationships among alpha-synuclein deposition, microglial infiltration, and
      NLRP3 inflammasome-related proteins (NLRP3, ASC, and Caspase 1) were
      quantitatively analyzed. Double-labeling immunofluorescence staining confirmed
      colocalization of NLRP3 inflammasome-related proteins and Cluster of
      Differentiation 68. We demonstrated that the density of microglia expressing
      NLRP3 inflammasome-related proteins was increased in the putamina of MSA cases
      and was significantly related to the deposition of phosphorylated alpha-synuclein
      positive glial cytoplasmic inclusions, tyrosine hydroxylase-positive fiber loss,
      and gliosis of glial fibrillary acidic protein-positive astrocytes. Our study
      suggests that the NLRP3 inflammasome is significantly upregulated and correlates
      with the neurodegenerative process in MSA.

PMID- 30295794
TI  - Histopathologic Correlates of Familial Hemophagocytic Lymphohistiocytosis
      Isolated to the Central Nervous System.
AB  - Familial hemophagocytic lymphohistiocytosis (HLH) is an immune hyperactivation
      syndrome caused by mutations in genes associated with cytotoxic T-cell and NK
      cell function. While neurological manifestations frequently accompany systemic
      inflammation at initial presentation, isolated central nervous system (CNS)
      involvement is rare, and the histological correlates are not well described. We
      present 3 patients (ages 5, 6, and 7 years) with CNS-isolated familial HLH, who
      presented with a variety of neurological symptoms and underwent brain biopsies
      for multifocal enhancing supratentorial and infratentorial lesions. Biopsy slides
      from all 3 patients revealed similar findings: perivascular lymphocytes,
      predominantly CD3+ T-cells (CD4>CD8) with occasional intramural infiltration of
      small vessels; scattered histiocytes without hemophagocytosis; parenchymal and
      leptomeningeal inflammation varying from mild and focal to severe and sheet-like
      with associated destructive lesions. There was no evidence of demyelination,
      neoplasia, or infection. Genetic testing identified compound heterozygous
      mutations in PRF1 (Patients 1 and 2) and UNC13D (Patient 3), with no evidence of
      systemic disease except decreased NK-cell function. All 3 patients were treated
      with hematopoietic stem cell transplantation with marked improvement of symptoms.
      These findings combined with the poor outcomes associated with delayed diagnosis
      and lack of aggressive treatment highlight the need to consider HLH in the
      differential diagnosis of inflammatory brain lesions.

PMID- 30295795
TI  - New sternal closure methods versus the standard closure method: systematic review
      and meta-analysis.
AB  - OBJECTIVES: This study aimed to evaluate, by means of a systematic review, the
      efficiency of new methods for sternal closure in order to prevent sternal wound
      complications after sternotomy. METHODS: The method of study was a systematic
      review of randomized clinical trials. We included studies that used rigid plates,
      thermoreactive clips, cables and flat wires, in comparison with the standard
      closure method. Patients included adults, regardless of gender and race. RESULTS:
      Seven clinical trials were included involving 1810 patients. Five trials were
      carried out in the USA, 1 in Australia and 1 in Italy, and the trials include
      both male and female patients. The included studies compared conventional sternal
      closure with new closure methods (rigid plate, thermoreactive clips, cables and
      flat wires). The new sternal closure methods make little or no difference
      compared to the standard closure when we analyse deep sternal wound infection
      [risk ratio 0.38, 95% confidence interval (CI) 0.02-7.63; I2 = 74%; 5 studies],
      superficial wound infection (risk ratio 1.34, 95% CI 0.46-3.92; I2 = 11%, 3
      studies) and death (risk ratio 1.16, 95% CI 0.42-3.21; I2 = 0%, 3 studies), but
      pain score was lower in new sternal closure methods (mean difference -0.57, 95%
      CI -0.98 to -0.16, I2 = 0%, 3 studies). There were no meta-analyses of sternal
      union, hospital stay, reoperation or mechanic ventilation time because of the
      high heterogeneity between the studies in terms of these outcomes. CONCLUSIONS:
      New sternal closure methods probably make little or no difference regarding the
      prevention of sternal complications in the postoperative period when compared to
      the standard closure method.

PMID- 30295796
TI  - A randomized phase II/III trial of conventional paclitaxel and carboplatin with
      or without bevacizumab vs dose-dense paclitaxel and carboplatin with or without
      bevacizumab, in stage IVB, recurrent or persistent cervical carcinoma: Japan
      Clinical Oncology Group Study (JCOG1311).
AB  - A randomized controlled trial has been initiated to compare chemotherapy
      containing dose-dense paclitaxel plus carboplatin with or without bevacizumab to
      a conventional regimen containing tri-weekly paclitaxel plus carboplatin with or
      without bevacizumab. Eligible patients are those with stage IVB, recurrent or
      persistent cervical carcinoma not amenable to curative treatment with local
      therapy. Patients are randomly assigned to either the conventional or dose-dense
      regimen. However, patients who are at increased risk of adverse events following
      bevacizumab administration will not receive this drug. The primary endpoint of
      phase II part is response rate. If the response rate of the dose-dense regimen is
      better than that of conventional regimen, this study will proceed to phase III,
      where the primary endpoint is overall survival. Secondary endpoints in phase III
      part are progression-free survival, response rates, adverse events, serious
      adverse events and the proportion of non-hospitalization periods compared with
      planned treatment periods.

PMID- 30295798
TI  - Real-world implications of QT prolongation in patients receiving voriconazole and
      amiodarone.
AB  - Objectives: Voriconazole, a triazole antifungal, is frequently prescribed in a
      complex patient population with comorbidities that require concomitant
      administration of QT interval-prolonging medications. We sought to evaluate QT
      interval prolongation in patients receiving concomitant therapy with voriconazole
      and amiodarone and to assess the development of any potentially fatal cardiac
      arrhythmias as a result. Methods: We conducted a retrospective observational
      study of patients who had received amiodarone and voriconazole concomitantly
      between 2005 and 2015, with a prior period of monotherapy, who had ECG data
      during monotherapy (baseline) and concomitant therapy (follow-up). Results: We
      included 46 patients in our final analysis. Overall, the mean change in QT
      corrected (QTc) from baseline to follow-up was 49.0 ms (P < 0.001). Eighteen
      (39.1%) patients had a follow-up QTc interval >=500 ms, with 17 (37.0%) having a
      change in QTc interval >=60 ms from baseline to follow-up. Men were more likely
      to have a follow-up QTc interval of >=500 ms. In multivariate analysis, only low
      serum potassium concentration and concomitant 'possible' QT-prolonging drugs were
      associated with a follow-up QTc interval >=500 ms and a lower baseline QTc
      interval was associated with a change in QTc interval of >=60 ms. Discharge
      diagnoses of cardiac arrhythmias and events were assessed and none was found to
      be related to concomitant therapy. Conclusions: Concomitant therapy with
      amiodarone and voriconazole significantly prolonged the QTc interval to a degree
      greater than that on monotherapy. However, no clinically significant cardiac
      events were observed.

PMID- 30295800
TI  - Corrigendum.

PMID- 30295797
TI  - Heart failure and diabetes: metabolic alterations and therapeutic interventions:
      a state-of-the-art review from the Translational Research Committee of the Heart
      Failure Association-European Society of Cardiology.

PMID- 30295799
TI  - IgG4-related disease: a new challenging diagnosis mimicking lung cancer.
AB  - IgG4-related disease (IgG4-RD) is a progressive inflammatory disease that might
      rarely involve only the lungs. We retrospectively reviewed the preoperative,
      clinical and surgical features of patients with a pathology highly suggestive or
      probable diagnosis of IgG4-RD without extra-thoracic involvement. Five patients
      were selected, 2 were operated on the right side. Positron emission tomography
      computed tomography (PET-CT) showed an uptake in all the patients (median 5.5),
      and 2 patients had an uptake at the thoracic lymph nodes. Two diagnoses were made
      through a CT-guided needle biopsy, while 3 were determined based on a lung wedge
      resection. The levels of serum IgG4 were elevated (>1.35 g/dl) in all the
      patients. Two patients had a highly suggestive diagnosis of IgG4-RD, and 3
      patients had a probable diagnosis of IgG4-RD. The differential diagnosis between
      IgG4-RD and lung malignancies based only on radiological features is challenging
      and often requires histological confirmation. A careful preoperative workup and a
      multidisciplinary approach to PET-positive nodules might help to avoid
      unnecessary major lung resections.

PMID- 30295802
TI  - Integrative genomic analysis reveals novel regulatory mechanisms of eyeless
      during Drosophila eye development.
AB  - Eyeless (ey) is one of the most critical transcription factors for initiating the
      entire eye development in Drosophila. However, the molecular mechanisms through
      which Ey regulates target genes and pathways have not been characterized at the
      genomic level. Using ChIP-Seq, we generated an endogenous Ey-binding profile in
      Drosophila developing eyes. We found that Ey binding occurred more frequently at
      promoter compared to non-promoter regions. Ey promoter binding was correlated
      with the active transcription of genes involved in development and transcription
      regulation. An integrative analysis revealed that Ey directly regulated a broad
      and highly connected genetic network, including many essential patterning
      pathways, and known and novel eye genes. Interestingly, we observed that Ey could
      target multiple components of the same pathway, which might enhance its control
      of these pathways during eye development. In addition to protein-coding genes, we
      discovered Ey also targeted non-coding RNAs, which represents a new regulatory
      mechanism employed by Ey. These findings suggest that Ey could use multiple
      molecular mechanisms to regulate target gene expression and pathway function,
      which might enable Ey to exhibit a greater flexibility in controlling different
      processes during eye development.

PMID- 30295801
TI  - Mapping interfacial hydration in ETS-family transcription factor complexes with
      DNA: a chimeric approach.
AB  - Hydration of interfaces is a major determinant of target specificity in
      protein/DNA interactions. Interfacial hydration is a highly variable feature in
      DNA recognition by ETS transcription factors and functionally relates to cellular
      responses to osmotic stress. To understand how hydration is mediated in the
      conserved ETS/DNA binding interface, secondary structures comprising the DNA
      contact surface of the strongly hydrated ETS member PU.1 were substituted, one at
      a time, with corresponding elements from its sparsely hydrated relative Ets-1.
      The resultant PU.1/Ets-1 chimeras exhibited variably reduced sensitivity to
      osmotic pressure, indicative of a distributed pattern of interfacial hydration in
      wildt-ype PU.1. With the exception of the recognition helix H3, the chimeras
      retained substantially high affinities. Ets-1 residues could therefore offset the
      loss of favorable hydration contributions in PU.1 via low-water interactions, but
      at the cost of decreased selectivity at base positions flanking the 5'-GGA-3'
      core consensus. Substitutions within H3 alone, which contacts the core consensus,
      impaired binding affinity and PU.1 transactivation in accordance with the
      evolutionary separation of the chimeric residues involved. The combined
      biophysical, bioinformatics and functional data therefore supports hydration as
      an evolved specificity determinant that endows PU.1 with more stringent sequence
      selection over its ancestral relative Ets-1.

PMID- 30295803
TI  - Trajectories and Predictors of Longitudinal Preexposure Prophylaxis Adherence
      Among Men Who Have Sex With Men.
AB  - Background: Adherence is necessary for efficacy of preexposure prophylaxis
      (PrEP), and text-messaging methods are promising tools for both adherence
      assessment and support. Although PrEP adherence is variable, little research has
      examined patterns of variability or factors associated with longitudinal use.
      Methods: In the context of a randomized controlled trial of text-messaging versus
      standard of care for PrEP adherence, 181 men who have sex with men received once
      daily tenofovir disoproxil fumarate/emtricitabine and daily adherence texts for
      48 weeks. Growth mixture modeling (GMM) was used to identify subgroups of
      individuals with similar trajectories of text-reported adherence. Between-group
      differences in pharmacologic measures of adherence (ie, tenofovir diphosphate and
      emtricitabine triphosphate levels), as well as predictors and study-end attitudes
      associated with group membership, were examined. Results: GMM identified 4
      trajectories of text-reported adherence. Classes with higher text-reported
      adherence had higher drug concentrations. Younger age and minority race were
      associated with lower adherence, and individuals in classes with lower adherence
      had greater baseline levels of depression, substance use concerns, and sexual
      risk. Differences in study satisfaction were also associated with adherence.
      Conclusions: This study supports the use of text-reported PrEP adherence.
      Identifying factors associated with less-than-optimal adherence may aid
      clinicians in anticipating at-risk patients requiring augmented intervention.
      Clinical trials registration: NCT01761643.

PMID- 30295804
TI  - Non-malignant and malignant meningioma incidence and survival in the elderly from
      2005-2015 using the Central Brain Tumor Registry of the United States.
AB  - Background: Meningioma incidence increases significantly with age. In the
      expanding elderly population, we lack complete understanding of population-based
      trends in meningioma incidence/survival. We provide an updated, comprehensive
      analysis of meningioma incidence and survival for individuals aged over 65.
      Methods: Data were obtained from the Central Brain Tumor Registry of the United
      States (CBTRUS) from 2005-2015 for non-malignant and malignant meningioma. Age
      adjusted incidence rates per 100,000 person-years were analyzed by age, sex,
      race, ethnicity, location, and treatment modalities. Survival was analyzed using
      Kaplan-Meier and multivariable Cox proportional hazards models for a subset of
      CBTRUS data. Results: Non-malignant meningioma incidence doubled from adults age
      65-69 years to adults over age 85 years and was significantly greater in females
      than males for all ages. Malignant meningioma incidence did not differ by sex for
      any age grouping. Non-malignant and malignant meningioma incidence was
      significantly greater in Black populations versus others. Non-malignant
      meningioma survival was worse with age, in Black populations, and in males,
      including when analyzed by five-year age groups. Surgical resection and radiation
      did not improve survival compared to resection alone in non-malignant meningioma.
      Conclusions: This study reports increasing non-malignant meningioma incidence in
      the elderly, increased incidence in Black populations, and in females. In
      contrast, malignant meningioma incidence did not differ between sexes. Risk of
      death was higher for Black individuals and males. Additionally, radiation did not
      confer a survival advantage when combined with resection for non-malignant
      meningioma. Thus, we identify clinically relevant discrepancies in meningioma
      incidence/survival that require further study.

PMID- 30295805
TI  - Quality assessment indicators in antenatal care worldwide: a systematic review.
AB  - Purpose: To describe indicators used for the assessment of antenatal care (ANC)
      quality worldwide under the World Health Organization (WHO) framework and based
      on a systematic review of the literature. Data sources: Searches were performed
      in MEDLINE, SciELO, BIREME and Web of Science for eligible studies published
      between January 2002 and September 2016. Study selection: Original articles
      describing women who had received ANC, any ANC model and, any ANC quality
      indicators were included. Data extraction: Publication date, study design and ANC
      process indicators were extracted. Results of data synthesis: Of the total
      studies included, 69 evaluated at least one type of ANC process indicator.
      According to WHO ANC guidelines, 8.7% of the articles reported healthy eating
      counseling and 52.2% iron and folic acid supplementation. The evaluation
      indicators on maternal and fetal interventions were: syphilis testing (55.1%),
      HIV testing (47.8%), gestational diabetes mellitus screening (40.6%) and
      ultrasound (27.5%). Essential ANC activities assessment ranged from 26.1% report
      of fetal heart sound, 50.7% of maternal weight and 63.8% of blood pressure.
      Regarding preventive measures recommended by WHO, tetanus vaccine was reported in
      60.9% of the articles. Interventions performed by health services to improve use
      and quality of ANC care, promotion of maternal and fetal health, and the number
      of visits to the ANC were evaluated in 65.2% of the studies. Conclusion: Numerous
      ANC content indicators are being used to assess ANC quality. However, there is a
      need to use standardized indicators across countries and efforts to improve
      quality evaluation.

PMID- 30295806
TI  - Fatal Granulomatous Amebic Encephalitis in a Heart Transplant Patient: Clinical,
      Radiographic, and Autopsy Findings.
AB  - Granulomatous amebic encephalitis is a rare necrotizing infection of the CNS that
      occurs most commonly in immunocompromised individuals and is usually fatal. It is
      difficult to diagnose as the clinical symptoms and radiographic findings are
      often mistaken for other bacterial, viral, fungal, or protozoan infections.
      Herein, we present the case of a 69-year-old heart transplant recipient who
      suffered fulminant neurological decline ~5 months after transplant. Extensive
      radiographic and laboratory testing did not provide a definite anatomic diagnosis
      and, despite aggressive clinical treatment, he died. An autopsy examination
      demonstrated numerous brain abscesses which contained amebic trophozoites and
      cysts. An indirect immunofluorescence assay performed at the Centers for Disease
      Control confirmed the presence of Acanthamoeba species. To the best of our
      knowledge, only 13 other cases of Acanthamoeba amebic encephalitis have been
      reported in patients who have received solid organ transplants and this is the
      second case reported in a heart transplant recipient. This case emphasizes that
      amebic encephalitis should be in the differential diagnosis for immunocompromised
      patients with new brain lesions found on radiographic imaging.

PMID- 30295808
TI  - A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase -
      extensive moonlighting in mitochondrial tRNA biogenesis.

PMID- 30295809
TI  - Detection of Drugs in Simultaneously Collected Samples of Oral Fluid and Blood.
AB  - Simultaneously collected samples of oral fluid and blood in a naturalistic
      setting could provide a qualitative impression of the relative detection times of
      drugs in oral fluid compared to blood. The aim of this study was to compare
      detections of different drugs in oral fluid and blood from a large material of
      paired samples. The study included results from 930 paired oral fluid and blood
      samples collected from drivers suspected for driving under the influence of
      drugs. Oral fluid was collected using the Intercept device. Blood samples were
      screened using an ultra high-performance liquid chromatography-tandem mass
      spectrometry (UHPLC-MS-MS) method and positive results were confirmed and
      quantified with a different analytical method. Oral fluid samples were analyzed
      using UHPLC-MS-MS. The drugs included in the study were: amphetamine,
      methamphetamine, tetrahydrocannabinol (THC), diazepam, N-desmethyldiazepam,
      clonazepam, alprazolam, nitrazepam, oxazepam, morphine, 6-monoacetylmorphine (6
      MAM), methadone and buprenorphine. The drugs detected more frequently in oral
      fluid compared to blood were amphetamine (497 positive in oral fluid/408 positive
      in blood), methamphetamine (332/232), oxazepam (106/36), morphine (65/31) and 6
      MAM (19/0). The drugs detected less frequently in oral fluid compared to blood
      were THC (224 positive in oral fluid/407 positive in blood), diazepam (137/160),
      N-desmethyldiazepam (183/188), clonazepam (148/307), alprazolam (47/68),
      nitrazepam (16/29) and buprenorphine (31/59). For methadone, the number of
      detections was the same in oral fluid and in blood (23/23). The results indicate
      that for amphetamine, methamphetamine, morphine and 6-MAM, relative detection
      time is longer in oral fluid than in blood, while for benzodiazepines, the
      results indicate that relative detection time is shorter in oral fluid than in
      blood. For oxazepam and buprenorphine, the results were dependent on the cut-off
      limits used. Regarding THC, the detection time in oral fluid depends on the
      sampling method. The relative detection time was shorter than in blood when using
      the Intercept device.

PMID- 30295807
TI  - Treatments targeting inotropy.
AB  - Acute heart failure (HF) and in particular, cardiogenic shock are associated with
      high morbidity and mortality. A therapeutic dilemma is that the use of positive
      inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is
      associated with increased mortality. Newer drugs, such as levosimendan or
      omecamtiv mecarbil, target sarcomeres to improve systolic function putatively
      without elevating intracellular Ca2+. Although meta-analyses of smaller trials
      suggested that levosimendan is associated with a better outcome than dobutamine,
      larger comparative trials failed to confirm this observation. For omecamtiv
      mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in
      patients with acute and chronic HF, and a Phase III morbidity/mortality trial in
      patients with chronic HF has recently begun. Here, we review the
      pathophysiological basis of systolic dysfunction in patients with HF and the
      mechanisms through which different inotropic agents improve cardiac function.
      Since adenosine triphosphate and reactive oxygen species production in
      mitochondria are intimately linked to the processes of excitation-contraction
      coupling, we also discuss the impact of inotropic agents on mitochondrial
      bioenergetics and redox regulation. Therefore, this position paper should help
      identify novel targets for treatments that could not only safely improve systolic
      and diastolic function acutely, but potentially also myocardial structure and
      function over a longer-term.

PMID- 30295810
TI  - Effect of exogenous butyrate on the gastrointestinal tract of sheep. I. Structure
      and function of the rumen, omasum, and abomasum.
AB  - The aim of this study was to determine the effect of exogenous butyrate on the
      structure and selected functions of the stomach in sheep. Eighteen rams (30.8 +/-
      2.1 kg; 12 to 15 mo of age) were allocated to the study and fed a diet for 14 d
      without (CTRL) or with sodium butyrate (BUT; 36 g/kg of offered DM). Neither DMI
      nor initial BW differed between treatments (P >= 0.61), but final BW was greater
      for BUT compared with CTRL (P = 0.03). Butyrate concentration in the
      reticuloruminal fluid and abomasal digesta was greater for BUT compared with CTRL
      (P <= 0.01), but total short-chain fatty acids (SCFA) concentration, as well as
      concentration of other SCFA, did not differ between treatments (P >= 0.07).
      Relative to BW, reticuloruminal tissue mass tended (P = 0.09) to be greater and
      omasal digesta was less (P = 0.02) for BUT compared with CTRL. Dietary butyrate
      did not affect ruminal papillae length, width, and density nor did it affect
      ruminal epithelium thickness (P >= 0.12) in the ventral sac of the rumen.
      However, the DM of ruminal epithelium (mg/cm2) tended (P = 0.06) to be greater
      for BUT compared with CTRL. Omasal and abomasal epithelium thicknesses were
      greater (P <= 0.05) for BUT compared with CTRL. Mitosis-to-apoptosis ratio in the
      abomasal epithelium was less for BUT compared with CTRL (P = 0.04). Finally, the
      mRNA expression of peptide transporter 1 in the omasal epithelium was less (P =
      0.02) and mRNA expression of monocarboxylate transporter 1 in the abomasal
      epithelium tended (P = 0.07) to be greater for BUT compared with CTRL. It can be
      concluded that exogenous butyrate supplementation affected not only the rumen but
      also omasum and abomasum in sheep.

PMID- 30295811
TI  - Fecal Calprotectin Responses Following Induction Therapy With Vedolizumab in
      Moderate to Severe Ulcerative Colitis: A Post Hoc Analysis of GEMINI 1.
AB  - Background: In patients with ulcerative colitis (UC), fecal calprotectin (FC)
      concentrations correlate with endoscopic inflammation evidence. This study
      investigated the effect of vedolizumab induction on FC concentrations and whether
      FC concentrations could be a reliable surrogate measure of disease status.
      Methods: Data from the placebo-controlled, phase 3 trial GEMINI 1 were used to
      evaluate week-6 relationships between outcomes (including clinical remission,
      mucosal healing [MH], and endoscopic remission) and both absolute FC
      concentration values and relative FC concentration changes from baseline (%FC0
      6). Sensitivity and specificity were calculated by cross-tabulation; the value of
      week-6 FC concentration as surrogate biomarker was measured with Youden J
      statistic computed for various cut points. Results: GEMINI 1 induction phase
      enrolled 895 patients. Fecal calprotectin concentration decreases were deeper in
      patients with clinical remission, MH, and/or endoscopic remission than in
      patients without. The best week-6 indicator of clinical or endoscopic remission
      in this data set was absolute FC concentration <=150 ug/g. The surrogate
      biomarker values (based on areas under the curve) for the best-performing cut
      points (FC0-6 reduction >90%, FC <=150 ug/g) were fair (range, 0.70-0.77, total
      population). More patients met the <=150 ug/g cut point with vedolizumab than
      with placebo. Baseline FC concentrations were not correlated with clinical
      outcomes. Conclusions: Fecal calprotectin concentration reductions were greater
      with vedolizumab induction than with placebo. Week-6 FC concentrations had only
      fair surrogate biomarker value for endoscopic status. Our data suggest that,
      while FC may reflect inflammatory burden, FC concentration after vedolizumab
      induction may not be a robust biomarker of mucosal inflammation.

PMID- 30295812
TI  - Illuminating Endocrine Evolution: The Power and Potential of Large-Scale
      Comparative Analyses.
AB  - Hormones are central mediators of genotype-phenotype and organism-environment
      interactions. Despite these important functions, the role of selection in shaping
      hormonal mediators of phenotype remains poorly understood. Thanks to decades of
      work by endocrinologists, circulating hormone levels have been measured in a
      diversity of organisms. Variation in other endocrine traits and mediators (e.g.,
      receptor expression and binding globulins), and the hormonal response to
      standardized challenges (e.g., restraint, pharmacological challenges) are also
      increasingly measured in both captive and free-living populations. Large-scale
      comparative analyses of the multitude of available endocrine data represent a
      particularly promising approach to addressing the function and evolution of these
      key phenotypic mediators, and their potential to serve as indicators of
      disturbance. Several recent phylogenetic comparative analyses and meta-analyses
      have begun to reveal the power and potential of these approaches to address key
      questions in integrative biology. Here we highlight two recent developments that
      are facilitating such analyses: increasingly powerful and flexible phylogenetic
      comparative methods, and the release of two endocrine trait databases-HormoneBase
      (currently 474 species) and the Wildlife Endocrinology Information Network
      (currently 25 species)-that contain compiled measures of endocrine traits across
      vertebrates. Increasingly comprehensive comparative analyses of endocrine data
      could provide insight into many interesting questions, including how rapidly
      changing environments are impacting phenotypes, why endocrine traits differ so
      remarkably within and across populations, and the evolution of plasticity. The
      endocrine system mediates interactions between genotypes and phenotypes, and
      between organisms and their environment. Environmentally induced hormonal
      responses regulate phenotypic flexibility across timescales by altering
      physiological state, gene expression, and epigenetic marks. A staggering
      diversity of phenotypic traits are mediated by hormones from early development
      through senescence. Through their actions on behavior, hormones also exert
      widespread influence over how organisms interact with their biotic and abiotic
      environments. Because hormones are responsive to the environment, there has long
      been interest in their use as biomarkers of exposure to challenges. More
      recently, increasing attention has been paid to the potential for within and
      among-population variation in endocrine regulation or responsiveness to serve as
      indicators of resistance or resilience to future challenges, or measures of
      evolutionary potential.

PMID- 30295813
TI  - The Temporal and Environmental Context of Early Animal Evolution: Considering All
      the Ingredients of an "Explosion".
AB  - Animals originated and evolved during a unique time in Earth history-the
      Neoproterozoic Era. This paper aims to discuss (1) when landmark events in early
      animal evolution occurred, and (2) the environmental context of these
      evolutionary milestones, and how such factors may have affected ecosystems and
      body plans. With respect to timing, molecular clock studies-utilizing a diversity
      of methodologies-agree that animal multicellularity had arisen by ~800 million
      years ago (Ma) (Tonian period), the bilaterian body plan by ~650 Ma (Cryogenian),
      and divergences between sister phyla occurred ~560-540 Ma (late Ediacaran). Most
      purported Tonian and Cryogenian animal body fossils are unlikely to be correctly
      identified, but independent support for the presence of pre-Ediacaran animals is
      recorded by organic geochemical biomarkers produced by demosponges. This view of
      animal origins contrasts with data from the fossil record, and the taphonomic
      question of why animals were not preserved (if present) remains unresolved.
      Neoproterozoic environments demanding small, thin, body plans, and lower
      abundance/rarity in populations may have played a role. Considering environmental
      conditions, geochemical data suggest that animals evolved in a relatively low
      oxygen ocean. Here, we present new analyses of sedimentary total organic carbon
      contents in shales suggesting that the Neoproterozoic ocean may also have had
      lower primary productivity-or at least lower quantities of organic carbon
      reaching the seafloor-compared with the Phanerozoic. Indeed, recent modeling
      efforts suggest that low primary productivity is an expected corollary of a low
      O2 world. Combined with an inability to inhabit productive regions in a low-O2
      ocean, earliest animal communities would likely have been more food limited than
      generally appreciated, impacting both ecosystem structure and organismal
      behavior. In light of this, we propose the "fire triangle" metaphor for
      environmental influences on early animal evolution. Moving toward consideration
      of all environmental aspects of the Cambrian radiation (fuel, heat, and oxidant)
      will ultimately lead to a more holistic view of the event.

PMID- 30295814
TI  - Clostridioides difficile: a potential source of NpmA in the clinical environment.

PMID- 30295815
TI  - Conflicts of Interest in Clinical Practice Guidelines.

PMID- 30295816
TI  - HPT-Axis Effects and Urinary Detection Following Clomiphene Administration in
      Males.
AB  - Context: Clomiphene is a commonly abused performance-enhancing drug by males in
      sport, but the extent to which testosterone increases in healthy males following
      its use is unknown. Additionally, evidence has suggested that clomiphene, a
      mixture of cis- and trans-isomers zuclomiphene and enclomiphene, is detectable in
      urine for months following use; the isomer-specific urinary detection window has
      yet to be characterized in a controlled study. Objective: To determine the effect
      of a once daily, 30-day clomiphene treatment on serum testosterone and
      gonadotropins in the subject population studied, and the urinary clearance and
      detection window of clomiphene isomers following administration for anti-doping
      purposes. Participants and Design: Twelve healthy males aged 25 to 38,
      representing a recreational athlete population, participated in this open-label,
      single-arm study. Intervention: Oral clomiphene citrate (50 mg) was self
      administered once daily for 30 days. Serum and urine samples were collected at
      baseline and at Day 7, 14, 21, 28, 30, 32, 35, 37, 44, 51, and 58; urine
      collections continued periodically up to Day 261. Results: Testosterone, LH, and
      FSH increased 146% (+/- 23% SEM), 177% (+/- 34%), and 170% (+/- 33%),
      respectively, during treatment compared to baseline. Serum drug concentrations
      and urinary excretion were non-uniform amongst individuals as isomeric
      concentrations varied. The zuclomiphene urinary detection window ranged from 121
      to greater than 261 days. Conclusions: Clomiphene significantly raises serum
      testosterone and gonadotropins in healthy men and thus can be abused as a
      performance-enhancing drug. Such abuse is detectable in urine for four months or
      greater following short-term use.

PMID- 30295817
TI  - A Wolf in Sheep's Clothing.

PMID- 30295818
TI  - Herpes Zoster Incidence in Inflammatory Bowel Disease Patients: A Population
      Based Study.
AB  - Background: The aberrant immune response in inflammatory bowel disease (IBD) and
      immunosuppression may intrinsically predispose patients to infectious
      complications, such as herpes zoster (HZ). We quantified the incidence of HZ in
      IBD patients in the province of Quebec, Canada. Methods: We performed a
      descriptive study using the provincial "Regie de l'Assurance Maladie du Quebec"
      (RAMQ) health registry from 1996 to 2015. The study population consisted of all
      subjects in the source population who fulfilled the CD and UC case-defining
      criteria. HZ incidence rates (IRs) in person-years (py) were calculated according
      to age groups, sex, Charlson Comorbidity index (CCI), and IBD type. Age
      standardized incidence ratios (SIRs) were performed using the Quebec general
      population as reference. Results: A total of 39,366 patients met the diagnostic
      criteria of either Crohn's disease (CD; n = 23,388), ulcerative colitis (UC; n =
      14,513), or IBD unclassified (n = 1465). We identified 2158 HZ cases. Crude IR
      was 6.67 cases/1000 py and 7.22 cases/1000 py for CD and UC patients,
      respectively. Unclassified IBD crude HZ IR was 7.54 cases/1000 py. No significant
      time trend was identified. HZ incidence is high in IBD patients >50 years of age
      and among the very young (0-17 years of age; SIR, 3.38; 95% confidence interval,
      2.64-4.26), especially females. Conclusions: These data suggest that HZ incidence
      is high in the IBD population. Preventives measures should be implemented in this
      at-risk population.

PMID- 30295819
TI  - Identification of new high affinity targets for Roquin based on structural
      conservation.
AB  - Post-transcriptional gene regulation controls the amount of protein produced from
      a specific mRNA by altering both its decay and translation rates. Such regulation
      is primarily achieved by the interaction of trans-acting factors with cis
      regulatory elements in the untranslated regions (UTRs) of mRNAs. These
      interactions are guided either by sequence- or structure-based recognition.
      Similar to sequence conservation, the evolutionary conservation of a UTR's
      structure thus reflects its functional importance. We used such structural
      conservation to identify previously unknown cis-regulatory elements. Using the
      RNA folding program Dynalign, we scanned all UTRs of humans and mice for
      conserved structures. Characterizing a subset of putative conserved structures
      revealed a binding site of the RNA-binding protein Roquin. Detailed functional
      characterization in vivo enabled us to redefine the binding preferences of Roquin
      and identify new target genes. Many of these new targets are unrelated to the
      established role of Roquin in inflammation and immune responses and thus
      highlight additional, unstudied cellular functions of this important repressor.
      Moreover, the expression of several Roquin targets is highly cell-type-specific.
      In consequence, these targets are difficult to detect using methods dependent on
      mRNA abundance, yet easily detectable with our unbiased strategy.

PMID- 30295820
TI  - Unstructured brainstorming is not enough: structured brainstorming based on four
      verification and validation questions yields better hazard identification in
      healthcare.
AB  - Objectives: (1) To introduce the Methodical Hazard Identification Checklist
      (MHIC) for structured brainstorming and the four V&V categories on which it is
      based, and (2) to compare its efficacy with that of brainstorming (BS) in
      identifying hazards in healthcare. Design: Comparative analysis of MHIC and team
      BS results. Setting: Baruch Padeh Medical Center, Poriya, Israel. Study
      participants: Quality engineering students, facilitators, validation teams and
      hospital staff who were familiar with the specific processes. Intervention(s):
      The number of hazards identified by team BS were compared with those deduced by
      applying the four V&V hazard categories to each step (the MHIC) of 10 medical and
      12 administrative processes. Main Outcome Measure(s): The total number of hazards
      (1) identified by BS, (2) identified by MHIC, (3) validated by the validation
      team and (4) hazards identified by both methods that the validation team deemed
      unreasonable. Results: MHIC was significantly more successful than BS in
      identifying all hazards for the 22 processes (P < 0.0001). The estimated
      probabilities of success for BS for administrative and medical processes were
      0.4444, 95%CI = [0.3506, 0.5424] and 0.3080, 95%CI = [0.2199, 0.4127],
      respectively. The estimated probabilities of success for MHIC for administrative
      and medical processes were 0.9885, 95%CI = [0.9638, 0.9964] and 0.9911, 95%CI =
      [0.9635, 0.9979], respectively. Conclusions: Compared to traditional BS, MHIC
      performs much better in identifying prospective hazards in the healthcare system.
      We applied MHIC methodology to administrative and medical processes and believe
      it can also be used in other industries that require hazard identification.

PMID- 30295821
TI  - Commutative regulation between endothelial NO synthase and insulin receptor
      substrate 2 by microRNAs.
AB  - Endothelial NO synthase (eNOS) expression is regulated by a number of
      transcriptional and post-transcriptional mechanisms, but the effects of competing
      endogenous RNAs (ceRNAs) on eNOS mRNA and the underlying mechanisms are still
      unknown. Our bioinformatic analysis revealed three highly expressed eNOS
      targeting miRNAs (miR-15b, miR-16, and miR-30b) in human endothelial cells (ECs).
      Among the 1103 mRNA targets of these three miRNAs, 15 mRNAs share a common
      disease association with eNOS. Gene expression and correlation analysis in
      patients with cardiovascular diseases identified insulin receptor substrate 2
      (IRS2) as the most correlated eNOS-ceRNA. The expression levels of eNOS and IRS2
      were coincidentally increased by application of laminar shear but reduced with
      eNOS or IRS2 siRNA transfection in human ECs, which was impeded by Dicer siRNA
      treatment. Moreover, luciferase reporter assay showed that these three miRNAs
      directly target the 3'-UTR of eNOS and IRS2. Overexpression of these three miRNAs
      decreased, whereas inhibition of them increased, both mRNA and protein levels of
      eNOS and IRS2. Functionally, silencing eNOS suppressed the Akt signal pathway,
      while IRS2 knockdown reduced NO production in ECs. Thus, we identified eNOS and
      IRS2 as ceRNAs and revealed a novel mechanism explaining the coincidence of
      metabolic and cardiovascular diseases.

PMID- 30295823
TI  - Commentary: Long-Term Update of Stereotactic Radiosurgery for Benign Spinal
      Tumors.

PMID- 30295822
TI  - Asymptomatic Natural Human Infections With the Simian Malaria Parasites
      Plasmodium cynomolgi and Plasmodium knowlesi.
AB  - Background: In Southeast Asia, Plasmodium knowlesi, a parasite of long-tailed
      macaques (Macaca fascicularis), is an important cause of human malaria.
      Plasmodium cynomolgi also commonly infects these monkeys, but only one naturally
      acquired symptomatic human case has been reported previously. Methods:
      Malariometric studies involving 5422 subjects (aged 6 months to 65 years) were
      conducted in 23 villages in Pailin and Battambang, western Cambodia. Parasite
      detection and genotyping was conducted on blood samples, using high-volume
      quantitative PCR (uPCR). Results: Asymptomatic malaria parasite infections were
      detected in 1361 of 14732 samples (9.2%). Asymptomatic infections with nonhuman
      primate malaria parasites were found in 21 individuals living close to forested
      areas; P. cynomolgi was found in 11, P. knowlesi was found in 8, and P. vivax and
      P. cynomolgi were both found in 2. Only 2 subjects were female, and 14 were men
      aged 20-40 years. Geometric mean parasite densities were 3604 parasites/mL in P.
      cynomolgi infections and 52488 parasites/mL in P. knowlesi infections. All P.
      cynomolgi isolates had wild-type dihydrofolate reductase genes, in contrast to
      the very high prevalence of mutations in the human malaria parasites.
      Asymptomatic reappearance of P. cynomolgi occurred in 2 subjects 3 months after
      the first infection. Conclusions: Asymptomatic naturally acquired P. cynomolgi
      and P. knowlesi infections can both occur in humans. Clinical Trials
      Registration: NCT01872702.

PMID- 30295824
TI  - Automated extraction of quality indicators for treatment of children with complex
      developmental disorders: A feasibility study using the example of attention
      deficit/hyperactivity disorder.
AB  - Quality issue: Quality assessment is challenging in children with developmental
      disorders. Previously, a set of quality indicators (QIs) was developed and
      analyzed in terms of feasibility of use with patients with attention
      deficit/hyperactivity disorder (ADHD). QI assessment turned out to be possible
      but highly complex. Thus, we compared different technologies for automated
      extraction of data for assessment of QIs. Choice of solution: Four automated
      extraction technologies (regular expressions, Apache Solr, Apache Mahout, Apache
      OpenNLP) were compared with respect to their properties regarding the complexity
      of implementing the QI, the complexity of implementing a check module, the
      reliability and quality of results, the complexity of preparation of
      interdisciplinary medical reports, and the complexity of deployment and
      installation. Implementation: Twenty medical reports from different institutions
      were reviewed for compliance with three QIs by these technologies and compared
      with expert opinions. Evaluation: Among the four technologies, Apache Solr had
      the best overall performance. For manual extraction of the three QIs, at least 77
      s were necessary per medical report, whereas the prototype evaluated and
      extracted the QIs automatically in 8 s on average. Unexpectedly, different
      assessments of the degree of compliance by the experts turned out to be one of
      the stumbling blocks. An in-depth evaluation compared results on a semantic
      level. Lessons learned: It is possible to extract QIs by post-processing
      automated technologies. This approach can also be applied to other developmental
      disorders. However, a more uniform documentation throughout institutions involved
      will be necessary in order to implement this method in daily practice.

PMID- 30295825
TI  - Application of machine learning algorithms for the differential diagnosis of
      peroxisomal disorders.
AB  - We have established diagnostic thresholds of very long-chain fatty acids (VLCFA)
      for the differential diagnosis of peroxisomal disorders using the machine
      learning tools. The plasma samples of 131 controls and 90 cases were tested for
      VLCFA using Gas chromatography-Mass spectrometry following stable isotope
      dilution. This data was used to construct association rules and for recursive
      partitioning. The C26/22 in healthy controls ranged between 0.008 - 0.01. The C26
      levels between 1.61 - 3.34 umol/L and C26/C22 between 0.05 - 0.10 are diagnostic
      of X-linked adrenoleukodystrophy (X-ALD). Very high levels of C26 (> 3.34 umol/L)
      and C26/C22 ratio (>0.10) are diagnostic of Zellweger syndrome (ZS). Significant
      elevation of phytanic acid was observed in Refsum (t = 6.14, p < 0.0001) and
      Rhizomelic chondrodysplasia punctata (RCDP) (t = 16.72, p < 0.0001). The C26/C22
      ratio is slightly elevated in RCDP (t = 2.58, p = 0.01) while no such elevation
      was observed in Refsum disease (t = 0.86, p = 0.39). The developed algorithm
      exhibited greater clinical utility (AUC: 0.99 - 1.00) in differentiating X-ALD,
      ZS, and healthy controls. The algorithm has greater clinical utility in the
      differential diagnosis of peroxisomal disorders based on VLCFA pattern.
      Plasmalogens will add additional value in differentiating RCDP and Refsum
      disease.

PMID- 30295826
TI  - Broad, Multi-Year Sampling Effort Highlights Complex Dynamics of the Tick-Borne
      Pathogen Ehrlichia chaffeensis (Rickettsiales: Anaplasmatacae).
AB  - Ehrlichia chaffeensis (Rickettsiales: Anaplasmatacae), an understudied bacterial
      pathogen emerging in the eastern United States, is increasing throughout the
      range of its vector, the lone star tick [Amblyomma americanum, L. (Acari:
      Ixodidae)]. To mitigate human disease risk, we must understand what factors drive
      E. chaffeensis prevalence. Here, we report patterns of E. chaffeensis prevalence
      in southeastern Virginia across 4 yr and ask how seasonal weather patterns affect
      variation in rates of E. chaffeensis occurrence. We collected A. americanum
      nymphs at 130 plots across southeastern Virginia in 2012, 2013, 2015, and 2016,
      and used polymerase chain reaction and gel electrophoresis to test for the
      presence of E. chaffeensis DNA. Prevalence estimates varied among years, ranging
      from 0.9% to 3.7%, and persistence of E. chaffeensis occurrence varied across
      space, with some sites never testing positive, and one site testing positive
      every year. Using generalized linear mixed-effects models, we related E.
      chaffeensis occurrence to temperature, humidity, vapor-pressure deficit, and
      precipitation during seasons up to 21 mo prior to sampling. Surprisingly, all
      support was lent to a positive effect of temperature during the previous fall and
      winter (i.e., prior to the nymphs' hatching), which we hypothesize to influence
      reservoir host population dynamics through changes to mortality or natality.
      Although further work is necessary to truly elucidate the mechanisms at play, our
      study shows E. chaffeensis distribution to be very dynamic across multiple
      dimensions, demanding broad concerted monitoring efforts that can consider both
      space and time.

PMID- 30295828
TI  - Commentary: Stereotactic Body Radiotherapy for Spinal Metastases at the Extreme
      Ends of the Spine: Imaging-Based Outcomes for Cervical and Sacral Metastases.

PMID- 30295827
TI  - Panel sequencing distinguishes monogenic forms of nephritis from nephrosis in
      children.
AB  - Background: Alport syndrome (AS) and atypical hemolytic-uremic syndrome (aHUS)
      are rare forms of chronic kidney disease (CKD) that can lead to a severe decline
      of renal function. Steroid-resistant nephrotic syndrome (SRNS) is more common
      than AS and aHUS and causes 10% of childhood-onset CKD. In recent years, multiple
      monogenic causes of AS, aHUS and SRNS have been identified, but their relative
      prevalence has yet to be studied together in a typical pediatric cohort of
      children with proteinuria and hematuria. We hypothesized that identification of
      causative mutations by whole exome sequencing (WES) in known monogenic nephritis
      and nephrosis genes would allow distinguishing nephritis from nephrosis in a
      typical pediatric group of patients with both proteinuria and hematuria at any
      level. Methods: We therefore conducted an exon sequencing (WES) analysis for 11
      AS, aHUS and thrombotic thrombocytopenic purpura-causing genes in an
      international cohort of 371 patients from 362 families presenting with both
      proteinuria and hematuria before age 25 years. In parallel, we conducted either
      WES or high-throughput exon sequencing for 23 SRNS-causing genes in all patients.
      Results: We detected pathogenic mutations in 18 of the 34 genes analyzed, leading
      to a molecular diagnosis in 14.1% of families (51 of 362). Disease-causing
      mutations were detected in 3 AS-causing genes (4.7%), 3 aHUS-causing genes (1.4%)
      and 12 NS-causing genes (8.0%). We observed a much higher mutation detection rate
      for monogenic forms of CKD in consanguineous families (35.7% versus 10.1%).
      Conclusions: We present the first estimate of relative frequency of inherited AS,
      aHUS and NS in a typical pediatric cohort with proteinuria and hematuria.
      Important therapeutic and preventative measures may result from mutational
      analysis in individuals with proteinuria and hematuria.

PMID- 30295829
TI  - Is a modified Global Trigger Tool method using automatic trigger identification
      valid when measuring adverse events?: A comparison of review methods using
      automatic and manual trigger identification.
AB  - Objectives: To evaluate a modified Global Trigger Tool (GTT) method with manual
      review of automatic triggered records to measure adverse events. Design: A cross
      sectional study was performed using the original GTT method as gold standard
      compared to a modified GTT method. Setting: Medium size hospital trust in
      Northern Norway. Participants: One thousand two hundred thirty-three records
      selected between March and December 2013. Main outcome measure: Records with
      triggers, adverse events and number of adverse events identified. Recall
      (sensitivity), precision (positive predictive value), specificity and Cohen's
      kappa with 95 % confidence interval were calculated. Results: Both methods
      identified 35 adverse events per 1000 patient days. The modified GTT method with
      manual review of 658 automatic triggered records identified adverse events (n =
      214) in 189 records and the original GTT method identified adverse events (n =
      216) in 186 records. One hundred and ten identical records were identified with
      adverse events by both methods. Recall, precision, specificity and reliability
      for records identified with adverse events were respectively 0.59, 0.58, 0.92 and
      0.51 for the modified GTT method. The total manual review time in the modified
      GTT method was 23 h while the manual review time using the original GTT method
      was 411 h. Conclusions: The modified GTT method is as good as the original GTT
      method that complies with the GTTs aim monitoring the rate of adverse events.
      Resources saved by using the modified GTT method enable for increasing the sample
      size. The automatic trigger identification system may be developed to assess
      triggers in real-time to mitigate risk of adverse events.

PMID- 30295830
TI  - Atypical haemolytic and uraemic syndrome: how can we protect the kidneys?

PMID- 30295831
TI  - Financial Conflicts of Interest in Inflammatory Bowel Disease Guidelines.
AB  - Background: Industry payments can lead to financial conflicts of interest (FCOI)
      among authors of clinical practice guidelines (CPGs). Guidelines for inflammatory
      bowel disease (IBD) may be at particularly high risk. We determined the
      prevalence of FCOI in IBD CPGs produced by various gastroenterology societies.
      Methods: We conducted a cross-sectional analysis of FCOI disclosure among CPGs
      related to the management of IBD. We ascertained the prevalence and types of FCOI
      for each guideline and determined adherence to National Academy of Medicine (NAM)
      standards. FCOI disclosures were compared between societies producing CPGs.
      Results: We identified 11 relevant CPGs with 173 total authors. There were 117
      (68%) authors who declared a payment. A total of 107 (62%) authors declared FCOI
      related to a medication recommended in the guideline. There was a significant
      difference (P < 0.001) between the proportion of authors with FCOI between
      countries or regions. Authors of US CPGs had a significantly lower FCOI
      prevalence (19%) compared with other societies. Authors of UK CPGs had a
      significantly lower FCOI prevalence (56%) compared with Canadian (84%) and
      European (94%) CPGs. Three (27%) guidelines adhered to both NAM standards.
      Conclusions: A substantial portion of authors of IBD CPGs had FCOI. Our study
      found a significant difference in FCOI prevalence based on CPG sponsor
      nationality. Most CPGs for IBD did not adhere to NAM standards for FCOI
      disclosure.

PMID- 30295832
TI  - Prevalence of HIV indicator conditions in late presenting patients with HIV: a
      missed opportunity for diagnosis?
AB  - Objective: To evaluate prevalence of HIV indicator conditions in late-presenters
      with HIV infection. Design: Retrospective cohort study between 2000 and 2014.
      Setting: Healthcare network in Melbourne, Australia. Participants: Patients
      presenting with late diagnosis of HIV infection (CD4<350 cells/MUL) compared to
      non-late presenting patients with HIV infection. Intervention: The European AIDS
      Clinical Society (EACS) guidelines on HIV indicator guided testing were used to
      assess for any indicator conditions in their prior medical history which
      represented a missed opportunity for earlier diagnosis. Main outcome measures:
      Descriptive statistics and prevalence of HIV indicator conditions. Results: Of
      436 patients with HIV infection, 82 were late presenters. Late presenters were
      more commonly male (83% vs 75%, p=0.11), older (mean age 45 vs 39 years), born
      overseas (61% vs 58%, p=0.68), and report heterosexual transmission as their
      exposure risk (51% vs 31%, p<0.001). Of 80 patients with late presentation of HIV
      infection, 54 (55%) had at least one, 29 (36%) at least two, 12 (15%) at least
      three and 5 (6%) had four or more previous HIV indicator conditions which would
      have triggered HIV testing according to guidelines. The most common indicator
      conditions were: unexplained loss of weight (31%), herpes zoster (10%),
      thrombocytopenia or leukopenia (10%), oral or oesophageal candidiasis (10%) and
      community acquired pneumonia (9%).Twenty-two patients (27.5%) had HIV indicator
      conditions diagnosed at least 12 months before the eventual diagnosis of HIV
      infection. Conclusion: Patients diagnosed with late-presenting HIV often had an
      HIV indicator condition prior to presentation, presenting a missed opportunity
      for earlier diagnosis.

PMID- 30295833
TI  - Morphological characterization of small hepatocytes after bile duct ligation in
      chicken.
AB  - Small hepatocytes have hepatocyte-like characteristics and high proliferation
      activity. Most small hepatocyte studies report on in vitro rat or human
      hepatocytes. Only a few studies of small hepatocytes after bile duct ligation
      have been reported, and none of these have focused on these cells in birds. In
      this study, small hepatocytes appearing in bile duct ligation chicken liver were
      examined using the morphological method with histological, immunohistochemical,
      and ultrastructural studies. Nine Boris Brown hens (over 744-d old) were used. In
      all chickens, both the common hepatoenteric duct and hepatocystic duct were
      ligated, and the livers were examined 1, 4, 6, 9, and 13 weeks after bile duct
      ligation. Histologically, the small cells were half the size of normal liver
      cells, and mitotic figures were often observed. The nuclei showed two forms:
      large and small. Many small cells were negative for periodic acid-Schiff stain,
      but positive cells were rarely observed. The cells existed in colonies on the
      side of the sinusoid of the hepatic lamina. Immunohistochemically, the small
      cells with large nuclei were strongly positive for CD44, albumin and
      proliferation cell nuclear antigen, and the cells with small nuclei were weakly
      positive. In the CD44-positive cell colony, negative cells were often observed to
      have mature hepatocyte-like morphology. Moreover, many of the cells were PAN
      cytokeratin negative. Ultrastructurally, the small cells had more nuclei with
      rich heterochromatin, poor cytoplasmic organelles, and narrow cytoplasm with a
      high electron density than mature hepatocytes. Moreover, cells having a middle
      ultrastructural characteristic existed between the small cells and mature
      hepatocytes. The small hepatocellular colony of the chicken appeared as a
      regeneration-related change in the liver after bile duct ligation. The cell had
      high cell proliferation activity and morphological, immunohistochemical, and
      ultrastructural characteristics similar to those of the mammalian small
      hepatocyte, as well as a similar progenitor cell.

PMID- 30295834
TI  - Primary pulmonary paraganglioma.

PMID- 30295836
TI  - Durable response to mTOR inhibition in a patient with relapsing papillary tumor
      of the pineal region.

PMID- 30295835
TI  - Controller protein of restriction-modification system Kpn2I affects transcription
      of its gene by acting as a transcription elongation roadblock.
AB  - C-proteins control restriction-modification (R-M) systems' genes transcription to
      ensure sufficient levels of restriction endonuclease to allow protection from
      foreign DNA while avoiding its modification by excess methyltransferase. Here, we
      characterize transcription regulation in C-protein dependent R-M system Kpn2I.
      The Kpn2I restriction endonuclease gene is transcribed from a constitutive, weak
      promoter, which, atypically, is C-protein independent. Kpn2I C-protein (C.Kpn2I)
      binds upstream of the strong methyltransferase gene promoter and inhibits it,
      likely by preventing the interaction of the RNA polymerase sigma subunit with the
      -35 consensus element. Diminished transcription from the methyltransferase
      promoter increases transcription from overlapping divergent C-protein gene
      promoters. All known C-proteins affect transcription initiation from R-M genes
      promoters. Uniquely, the C.Kpn2I binding site is located within the coding region
      of its gene. C.Kpn2I acts as a roadblock stalling elongating RNA polymerase and
      decreasing production of full-length C.Kpn2I mRNA. Mathematical modeling shows
      that this unusual mode of regulation leads to the same dynamics of accumulation
      of R-M gene transcripts as observed in systems where C-proteins act at
      transcription initiation stage only. Bioinformatics analyses suggest that
      transcription regulation through binding of C.Kpn2I-like proteins within the
      coding regions of their genes may be widespread.

PMID- 30295837
TI  - Mechanisms of high-level ceftolozane/tazobactam resistance in Pseudomonas
      aeruginosa from a severely neutropenic patient and treatment success from synergy
      with tobramycin.

PMID- 30295838
TI  - Changes in physical activity, weight and wellbeing outcomes among attendees of a
      weekly mass participation event: a prospective 12-month study.
AB  - Background: Mass participation events are recognized as a way of engaging low
      active individuals in health-enhancing physical activity, but there is a need to
      investigate the sustained effects on behaviour and health. This study aimed to
      examine changes in self-reported physical activity, weight and wellbeing over 12
      months in participants of parkrun, a weekly mass participation 5 km running
      event. Methods: New parkrun registrants (n = 354) completed self-reported
      measures of physical activity, weight, happiness and stress, at registration, 6
      months and 12 months. Objective data on attendance and fitness (i.e. run dates
      and finishing times) were obtained from the parkrun database. Results: Overall
      physical activity levels were high at baseline, but significantly increased over
      the first 6 months, before declining. By 12 months, weekly physical activity was
      39 min higher than baseline. Significant reductions in body mass index were
      observed over 12 months, with a weight loss of 1.1% in the whole sample, and 2.4%
      among overweight participants. Modest increases in happiness and decreases in
      perceived stress were recorded. Run times suggested a 12% improvement in fitness
      during the study. Conclusion: Significant changes in weight, fitness and
      wellbeing outcomes indicate the public health benefits of regular participation
      in parkrun.

PMID- 30295839
TI  - Linitis plastica: "leather bottle" stomach.

PMID- 30295840
TI  - Bioaccessibility of Drug Residues on Common Police Station Work Surfaces.
AB  - The fraction of any surface-adsorbed contaminant available for absorption is
      considered the bioaccessible fraction. Applied previously to contaminants such as
      pesticides and heavy metals on surfaces such as soil, food and cosmetics, the
      term may also be used to describe the fraction of drug residue bound to work
      surfaces which may be mobilized via contact transfer with human skin. Police
      station work surfaces have been shown to commonly contain low levels of drug
      residues as thin films; however, no information is available on how readily these
      residues may be transferred to human skin during direct or glancing contact. A
      bioaccessibility study was undertaken in which jojoba oil and artificial sebum
      were used to mimic human sebum to identify how readily a mix of six licit and
      illicit drugs were transferred from three commonly used police station work
      surfaces. Transfer from surfaces was slightly greater for jojoba oil than sebum
      when using a direct pressure contact or a wiping motion. Generally, less than 5%
      of applied residues were recovered via direct contact, and up to 10% when a
      wiping motion was used to simulate a glancing contact. While swabbing of work
      surfaces with methanol provides a suitable environmental audit of drug residues
      present, it does not represent the bioaccessible fraction of residues available
      for contact transfer, and hence, absorption via skin or unintentional ingestion.
      The current study indicates that the ability of sebum to mobilize drug residues
      from thin films on work surfaces via casual contact is limited, and sebum may
      potentially assist in the preservation of residues on pitted work surfaces and on
      skin.

PMID- 30295842
TI  - Separation and Identification of Isomeric and Structurally Related Synthetic
      Cannabinoids Using 2D Liquid Chromatography and High Resolution Mass
      Spectrometry.
AB  - Novel psychoactive substances (NPS) are emerging drugs of abuse that are
      variations of existing compounds intended to cause a CNS psychotropic effect.
      Some NPS are so comparable in structure and physicochemical properties that they
      co-elute using traditional single column chromatographic techniques and therefore
      will not be detected as individual compounds. 2D liquid chromatography (2D-LC)
      has demonstrated applicability in difficult separations of small molecules and
      compounds in complex mixtures. It was hypothesized that this technique could also
      be used to separate co-eluting isomeric and structurally related, non-isomeric
      NPS, including synthetic cannabinoids (SC). Initial studies assessed several
      parameters, including column type, mobile phase, analysis time, gradient and flow
      rate, to optimize a 2D-LC method for separation and analysis of SC. The final
      comprehensive on-line 2D-LC method employed a Bonus-RP column in the first
      dimension (1D) coupled with UV detection and a biphenyl column in the second
      dimension (2D) coupled with QTOF-MS detection in full scan positive mode. To test
      the utility of the method, three SC mixes were created, each containing five
      compounds that were unresolvable in a traditional, 1D-LC separation; one mix with
      isomeric compounds and two with structurally related but non-isomeric compounds.
      Contour plots of UV absorbance in 1D and MS ion intensity in 2D demonstrated that
      all components in each mixture were successfully resolved using the 2D-LC
      separation method. This research serves as proof-of-concept for the application
      of 2D-LC to the separation of isomeric and structurally related SC. With further
      optimization and validation, 2D-LC may be a generally useful tool for separation
      of complex mixtures of NPS.

PMID- 30295841
TI  - Structural basis of 5' flap recognition and protein-protein interactions of human
      flap endonuclease 1.
AB  - Human flap endonuclease 1 (hFEN1) is a structure-specific nuclease essential for
      DNA replication and repair processes. hFEN1 has 5' flap removal activity, as well
      as gap endonuclease activity that is critical for restarting stalled replication
      forks. Here, we report the crystal structures of wild-type and mutant hFEN1
      proteins in complex with DNA substrates, followed by mutagenesis studies that
      provide mechanistic insight into the protein-protein interactions of hFEN1. We
      found that in an alpha-helix forming the helical gateway of hFEN1 recognizes the
      5' flap prior to its threading into the active site for cleavage. We also found
      that the beta-pin region is rigidified into a short helix in R192F hFEN1-DNA
      structures, suppressing its gap endonuclease activity and cycle-dependent kinase
      interactions. Our findings suggest that a single mutation at the primary
      methylation site can alter the function of hFEN1 and provide insight into the
      role of the beta-pin region in hFEN1 protein interactions that are essential for
      DNA replication and repair.

PMID- 30295844
TI  - Systemic and Reflexive: Foundations of Cumulative Dis/Advantage and Life-Course
      Processes.

PMID- 30295843
TI  - Prehospital Resuscitation Performed on Hypotensive Trauma Patients in
      Afghanistan: The Prehospital Trauma Registry Experience.
AB  - Introduction: Hemorrhage is the leading cause of potentially preventable death on
      the battlefield. Hypotension in the setting of trauma portends a higher rate of
      mortality. We describe the interventions for trauma-related hypotension performed
      in the prehospital combat setting in accordance with Tactical Combat Casualty
      Care (TCCC) guidelines. Materials and Methods: We searched the Prehospital Trauma
      Registry for casualties from January 2013 to September 2014. Within that group,
      we searched for all casualties with documented hypotension by either measured
      systolic blood pressure <=90 mmHg or a weak or absent radial pulse documented by
      the prehospital provider. We used descriptive statistics to analyze the
      interventions performed in our study sample. Results: Of the 705 casualties
      available for query, 134 (19.0%) casualties with documented hypotension met
      inclusion criteria. Most casualties with hypotension had an alert mental status
      (70.1%), had a medical officer in their chain of care (59.0%), were Afghan
      (64.2%), and evacuated on an urgent status (78.4%). Explosives were the most
      frequent mechanism of injury (50.7%). There were 42 fluid administrations
      documented on 33 (24.6%) casualties. The most common fluid administered was
      normal saline (52.4%) followed by hetastarch solution (33.3%). There was one
      documented use of a fluid warmer in this cohort. One subject received four units
      of packed red blood cells. No other casualties had documented blood product
      administration. There were no documented administrations of PlasmaLyte. There
      were four casualties that received lactated Ringer's. Conclusion: Most casualties
      with documented hypotension after trauma in the Prehospital Trauma Registry did
      not receive prehospital blood or fluid intervention. Of the interventions
      performed, most did not match with contemporary TCCC guidelines.

PMID- 30295845
TI  - Emotional Understanding in Children with A Cochlear Implant.
AB  - Emotional understanding plays an important role in the physical and mental health
      of children. To determine whether the development of emotional understanding is
      delayed in children with a cochlear implant (CI), 30 children with a CI and 30
      matched children with typical hearing aged between 3 and 9 years old completed
      three tasks (facial expression, tone expression and scene of emotion matching),
      in which they identified four basic emotions (happiness, sadness, anger, and
      fear). The participants included 40 preschool children and 20 school-aged
      children. Compared with the children with typical hearing, the children with a CI
      were significantly delayed in the ability to understand emotion; the tone
      expression matching task was the most difficult task for all participants; and
      the school-aged children performed better than the preschool children, but this
      trend was only observed in the typical hearing group; and happiness was the
      easiest emotion to identify.

PMID- 30295846
TI  - The Ability of a Cytomegalovirus ELISPOT Assay to Predict Outcome of Low-Level
      CMV Reactivation in Hematopoietic Cell Transplant Recipients.
AB  - Background: CMV infections in hematopoietic cell transplant (HCT) recipients
      cause substantial morbidity and mortality. CMV cell-mediated immunity (CMV-CMI)
      can be determined by levels of interferon gamma (IFN-gamma) production using an
      ELISPOT CMV assay (T-SPOT.CMV assay). In this study, we evaluated the ability of
      this assay to predict the outcome of low-level CMV reactivation in HCT
      recipients. Methods: We followed 55 HCT recipients with low-level CMV
      reactivation up to 8 weeks from enrollment. Progression to clinically significant
      CMV infection (CS-CMVi) was defined as a CMV viral load > 1,000 IU/ml or > 500
      IU/ml in patients receiving matched related/autologous or matched unrelated
      transplants, respectively, and initiation of antiviral treatment. Results:
      Progression to CS-CMVi occurred in 31 (56%) of the HCT recipients. Spot counts of
      CMV-specific pp65 and IE1 antigens were significantly lower in patients who had
      CS-CMVi than in patients who did not. On multivariate analysis, the ELISPOT CMV
      responses and steroids use were the only predictors of progression to CS-CMVi.
      Conclusions: A strong association between low CMV-CMI and progression to CS-CMVi
      was observed in HCT recipients. The implementation of serial monitoring of CMV
      CMI may identify patients at risk of progression to CS-CMVi that require
      antiviral therapy.

PMID- 30295847
TI  - FLOWERING LOCUS T2 (FT2) regulates spike development and fertility in temperate
      cereals.
AB  - FLOWERING LOCUS T2 (FT2) is the closest paralog of the FT1 flowering gene in the
      temperate grasses. Here we show that overexpression of FT2 in Brachypodium
      distachyon and barley results in precocious flowering and reduced spikelet
      number, while downregulation by RNA interference results in delayed flowering and
      a reduced percentage of filled florets. Similarly, truncation mutations of FT2
      homeologs in tetraploid wheat delayed flowering (2-4 days) and reduced fertility.
      The wheat ft2 mutants also showed a significant increase in the number of
      spikelets per spike, with a longer spike development period potentially
      contributing to the delayed heading time. In the wheat leaves, FT2 was expressed
      later than FT1, suggesting a relatively smaller role for FT2 in the initiation of
      the reproductive phase. FT2 transcripts were detected in the shoot apical
      meristem and increased during early spike development. Transverse sections of the
      developing spike showed the highest FT2 transcript levels in the distal part,
      where new spikelets are formed. Our results suggest that, in wheat, FT2 plays an
      important role in spike development and fertility and a limited role in the
      timing of the transition between the vegetative and reproductive shoot apical
      meristem.

PMID- 30295848
TI  - Validity, Reliability, and Measurement Invariance of the Diabetes Stress
      Questionnaire-Short Form.
AB  - Objective: The purpose of this study was to develop a short form of the Diabetes
      Stress Questionnaire (DSQ) with adequate psychometric properties (i.e., internal
      consistency, convergent, criterion, discriminant validity, construct validity,
      and measurement invariance). Methods: In total, 181 youth with type 1 diabetes
      (T1D) completed the 65-item DSQ, and archival data were obtained from 142 youth
      with T1D to serve as an independent cross-validation sample. Twenty-four items
      were chosen to retain the original eight scales of the DSQ and to maximize
      internal consistency and correlations to full subscales. Confirmatory factor
      analyses were used to evaluate the proposed factor structure of the Diabetes
      Stress Questionnaire-Short Form (DSQ-SF) and to assess invariance of the DSQ-SF
      across sex, race, grade level, glycemic control, illness duration, and annual
      income categories. Results: The 24-item DSQ-SF was found to have good internal
      consistency, factor structure and fit, correlated highly to the full scale (r =
      .98), and was invariant across sex, race, grade level (<9th grade or >9th grade),
      glycemic control, illness duration, and annual income. Conclusions: The DSQ-SF
      appears to be a psychometrically robust measure of diabetes-specific stress in
      youth with T1D. Present findings suggest that the DSQ-SF has the potential to be
      a useful, quick, cost-effective, and comprehensive screening tool for identifying
      youth with T1D who may benefit from T1D-specific stress reduction interventions
      as a way to improve health behaviors, psychosocial well-being, and glycemic
      control.

PMID- 30295849
TI  - Simultaneous Detection and Quantification of Three Novel Prescription Drugs of
      Abuse (Suvorexant, Lorcaserin and Brivaracetam) in Human Plasma by UPLC-MS-MS.
AB  - Suvorexant (SVR), lorcaserin (LCR) and brivaracetam (BVR) have been recently
      approved for the treatment of insomnia, obesity and epilepsy, respectively.
      Despite their clinical uses, these drugs have some abuse potential and have been
      enlisted under the schedule IV (SVR, LVR) and schedule V (BVR) categories of the
      Controlled Substances Act. A sensitive UPLC-MS-MS assay was developed for
      simultaneously determining SVR, LCR and BVR in human plasma. The liquid-liquid
      extraction method, using tert-butyl methyl ether as an extracting solvent, was
      used for sample preparation. Chromatographic separation was performed by using
      the Acquity BEH C18 column, using 10 mM ammonium acetate/acetonitrile/formic acid
      (15/85/0.1%; v/v/v) as the mobile phase. For sample ionization, electrospray
      ionization was used in the positive-ion mode. The multiple-reaction monitoring
      mode was used for detecting and quantifying analytes by using separate precursor
      to-product ion transitions. The assay was validated following the SWGTOX
      guidelines, and all validation results were within the acceptable limits. The
      calibration curves of the analytes in the plasma were found to be linear, and the
      coefficient of determination (R2) was >= 0.992 for all the three analytes. The
      limit of detection values for SVR, LCR and BVR were 0.08, 0.11 and 0.26 ng/mL,
      respectively, whereas the limit of quantification values were 0.16, 0.27 and 0.65
      ng/mL, respectively. The assay developed in this study is suitable for the
      identification and quantification of SVR, LCR and BVR in the forensic laboratory.

PMID- 30295850
TI  - RNA-binding protein DDX1 is responsible for fatty acid-mediated repression of
      insulin translation.
AB  - The molecular mechanism in pancreatic beta cells underlying hyperlipidemia and
      insulin insufficiency remains unclear. Here, we find that the fatty acid-induced
      decrease in insulin levels occurs due to a decrease in insulin translation. Since
      regulation at the translational level is generally mediated through RNA-binding
      proteins, using RNA antisense purification coupled with mass spectrometry, we
      identify a novel insulin mRNA-binding protein, namely, DDX1, that is sensitive to
      palmitate treatment. Notably, the knockdown or overexpression of DDX1 affects
      insulin translation, and the knockdown of DDX1 eliminates the palmitate-induced
      repression of insulin translation. Molecular mechanism studies show that
      palmitate treatment causes DDX1 phosphorylation at S295 and dissociates DDX1 from
      insulin mRNA, thereby leading to the suppression of insulin translation. In
      addition, DDX1 may interact with the translation initiation factors eIF3A and
      eIF4B to regulate translation. In high-fat diet mice, the inhibition of insulin
      translation happens at an early prediabetic stage before the elevation of glucose
      levels. We speculate that the DDX1-mediated repression of insulin translation
      worsens the situation of insulin resistance and contributes to the elevation of
      blood glucose levels in obese animals.

PMID- 30295851
TI  - The jPOST environment: an integrated proteomics data repository and database.
AB  - Rapid progress is being made in mass spectrometry (MS)-based proteomics, yielding
      an increasing number of larger datasets with higher quality and higher
      throughput. To integrate proteomics datasets generated from various projects and
      institutions, we launched a project named jPOST (Japan ProteOme STandard
      Repository/Database, https://jpostdb.org/) in 2015. Its proteomics data
      repository, jPOSTrepo, began operations in 2016 and has accepted more than 10 TB
      of MS-based proteomics datasets in the past two years. In addition, we have
      developed a new proteomics database named jPOSTdb in which the published raw
      datasets in jPOSTrepo are reanalyzed using standardized protocol. jPOSTdb
      provides viewers showing the frequency of detected post-translational
      modifications, the co-occurrence of phosphorylation sites on a peptide and
      peptide sharing among proteoforms. jPOSTdb also provides basic statistical
      analysis tools to compare proteomics datasets.

PMID- 30295852
TI  - CREG1 promotes uncoupling protein 1 expression and brown adipogenesis in vitro.
AB  - Brown adipocytes play a critical role for adaptive thermogenesis to regulate body
      temperature in cold or to circumvent diet-induced obesity. In the present study,
      we investigated the role of cellular repressor of E1A-stimulated genes 1 (CREG1)
      on brown adipogenesis and uncoupling protein 1 (UCP1) expression by using in
      vitro culture models. In murine mesenchymal stem cell line C3H10T1/2, Creg1 mRNA
      expression significantly increased in a time-dependent manner along with Ucp1
      mRNA induction in brown adipogenesis. Creg1 gene overexpression upregulated the
      expression of brown fat-related genes including Ucp1 but its suppression
      downregulated these gene expression in C3H10T1/2 cells. Unlike the brown
      adipogenesis, Creg1 mRNA expression decreased significantly after differentiation
      stimulation in white adipogenesis of 3T3-L1 cells. Either Creg1 gene
      overexpression or suppression hardly affected white adipogenesis. In addition,
      CREG1 protein stimulated brown adipogenesis and rescued the adipogenesis in the
      absence of thyroid hormone in C3H10T1/2 cells. In reporter assay, CREG1 induction
      stimulated Ucp1 promoter activity, which was enhanced by co-expression with
      thyroid hormone receptors. The effect of CREG1 on Ucp1 promoter activity was also
      stimulated by retinoic acid. These results strongly suggest that CREG1 plays an
      important role on the regulation of UCP1 expression and brown adipogenesis.

PMID- 30295853
TI  - Portal hypertension, oesophageal varices & caput medusae.

PMID- 30295854
TI  - Feasibility of Training Physical Therapists to Implement a Psychologically
      Informed Physical Therapy Program for Deployed U.S. Sailors and Marines with
      Musculoskeletal Injuries: Corrigendum.

PMID- 30295855
TI  - Canola Oil as an Economical Lipid Source in Gel Larval Diet for Queensland Fruit
      Fly.
AB  - A new sterile insect technique (SIT) program is currently being developed for
      management of the Queensland fruit fly, Bactrocera tryoni (Froggatt) (Diptera:
      Tephritidae), the most costly challenge to Australian horticulture in the eastern
      states. SIT relies on cost-effective mass production of millions of high-quality
      flies. A recently developed gel larval diet has proven effective, enabling
      production of large numbers of high-quality flies, but includes some costly
      ingredients. With a basic diet now available, current research focuses on
      refining the formulation to deliver a more economical diet. Wheat germ oil (WGO)
      is the main lipid source in the current Queensland fruit fly gel diet, but is a
      particularly expensive ingredient and has limited availability. To identify an
      oil that maintains high productivity and fly quality at reduced cost, the present
      study assessed production and performance of Queensland fruit flies reared on gel
      larval diets containing the WGO that was used in previous studies (WGO/M), an
      alternative WGO (WGO/A), sunflower oil, rice bran oil, and canola oil. Diets
      containing canola oil ($5.24/liter) performed as well as diets with WGO/M
      ($116/liter) in terms of parental egg hatch, pupal number, pupal weight, adult
      emergence, percentage and rate of fliers, sex ratio, fecundity, and fertility (F1
      egg hatch), offering a remarkably cost-effective alternative. Costs of oil in
      Queensland fruit fly production are reduced by ca. 95% per 1,000 flight capable
      adults ('fliers'). Substantial savings may be made in Queensland fruit fly mass
      rearing by substituting WGO/M with canola oil in gel larval diets without
      compromising productivity.

PMID- 30295856
TI  - Internal carotid webs.

PMID- 30295857
TI  - Management decision of hospital surge: assessing seasonal upsurge in inpatient
      medical bed occupancy rate among public acute hospitals in Hong Kong.
AB  - Background: There were recurrent upsurges in demand for public hospital services
      in Hong Kong. An understanding of the contribution of some possible factors for
      the rise in health care burden would help to inform hospital management
      strategies. Aim: To evaluate the utilisation patterns of hospitalizations in
      medical wards among public acute hospitals in Hong Kong during surge periods.
      Design: Retrospective study. Methods: By extracting the information in press
      releases between 2014 and 2018, descriptive statistics about medical ward
      occupancy situation during six surge periods were generated. A time series model
      was constructed to estimate the occupancy rate at each hospital and assess its
      relationship with the intensity of seasonal influenza activity, extreme weather,
      day of week and long holidays. Results: There was a significant increase in the
      number of admissions to medical wards in all six surge periods. A significant
      variation in occupancy rate between weekdays and geographic regions was observed.
      The occupancy rate in 10, out of 15, hospitals was significantly associated with
      the influenza activity, while there was limited effect of weather on the
      occupancy rate. A significant holiday effect was observed during Christmas and
      Chinese New Year, resulting in a lower bed occupancy rate. Conclusions: A
      differential burden in public hospitals during surge periods was reported.
      Contingency bed and staff management shall be tailored to individual hospitals,
      given their differences in the determinants for inpatient bed occupancy.

PMID- 30295858
TI  - A Gas Chromatography-Triple Quadrupole Mass Spectrometry Assay for the
      Quantification of Opiates in Human Blood Samples.
AB  - A simplified protein precipitation method in combination with gas chromatography
      triple quadrupole mass spectrometry (GC-MS-MS) analysis was developed and
      validated for the simultaneous determination of codeine, morphine, 6
      acetylmorphine (6-MAM), hydrocodone and hydromorphone in human blood samples. A
      protein precipitation with 10% trichloroacetic acid followed by solid-phase
      extraction using a mixed-mode cartridge was used to separate the analyte from the
      blood samples. A BSTFA + 1% TMCS was used for derivatization of opiates prior to
      the analysis. Codeine-D3, morphine-D3, 6-acetylmorphine-D3 and hydrocodone-D6
      were used as internal standards. The GC-MS-MS was operated under multiple
      reaction monitoring mode using electron ionization technique. The transition ions
      used for quantitation were 371 -> 234 for codeine, 429 -> 146 for morphine, 399 
      > 287 for 6-MAM, 299 -> 228 for hydrocodone and 357 -> 314 for hydromorphone. The
      method was linear over the concentration range 2.5-1000 ng/mL for all analytes,
      except hydrocodone which was linear over 5-1000 ng/mL with a correlation
      coefficient (r2) = 0.99. The limit of detection was 1.0 ng/mL for all compounds
      except hydrocodone which was 2.5 ng/mL. The limit of quantitation was 2.5 ng/mL
      for all compounds except hydrocodone which was 5.0 ng/mL. The precision (% RSD)
      was within 1.26-14.81 and the accuracy (% Bias) was within -6.29-10.93% for all
      compounds. The method successfully analyzed morphine (305 ng/mL) and 6
      acetylmorphine (6-MAM) (2.3 ng/mL) in a human blood sample received from an
      opiate user.

PMID- 30295860
TI  - ECG changes in acute aconite poisoning.

PMID- 30295859
TI  - Escherichia coli Rib Osteomyelitis.

PMID- 30295861
TI  - Monitoring of Resistance in Field Populations of Scirtothrips dorsalis
      (Thysanoptera: Thripidae) and Diaphorina citri (Hemiptera: Liviidae) to Commonly
      Used Insecticides in Citrus in Central India.
AB  - Field populations of thrips (Scirtothrips dorsalis Hood) from citrus nurseries
      and psyllids (Diaphorina citri Kuwayama) from commercial citrus orchards of three
      districts in Maharashtra State in India were evaluated for levels of resistance
      to organophosphates (acephate, chlorpyrifos, quinalphos, and dimethoate),
      neonicotinoids (thiamethoxam, imidacloprid), abamectin and spinosad between 2012
      and 2017. Leaf dip bioassays for thrips and shoot tip bioassay for nymph and
      adult psyllids were used to assess levels of insecticide resistance as indicated
      by resistance ratios (RRs). In general, levels of insecticide resistance were
      zero (RR = 1) or very low (RR = 2-10); however, we recorded 21.0- and 28.0-fold
      increase in resistance (RR = 21-50) to spinosad 45SC in S. dorsalis between 2016
      and 2017 that may be attributed to the continuous application of the insecticide
      for the management of various sucking insect pests of citrus. We found that
      levels of resistance to insecticides in adult and nymph D. citri collected from
      the three districts were zero to low (RR = 2-10). Our data show there may be a
      shift in resistance to neonicotinoid insecticides that are widely used among
      citrus growers in the study region. Results from this study indicate that the
      evolution of insecticide resistance and cross-resistance may be decelerated by
      the rotational use of insecticides with different modes of action.

PMID- 30295862
TI  - The G-matrix Simulator Family: Software for Research and Teaching.
AB  - Genetic variation plays a fundamental role in all models of evolution. For
      phenotypes composed of multiple quantitative traits, genetic variation is best
      quantified as additive genetic variances and covariances, as these values
      determine the rate and trajectory of evolution. Additive genetic variances and
      covariances are often summarized conveniently in the G-matrix, which has additive
      genetic variances for each trait on the diagonal and additive genetic covariances
      as its off-diagonal elements. The evolution of the G-matrix is an interesting
      topic in its own right, because the processes that affect trait means also affect
      the distribution of standing genetic variation, which, in turn, feeds back to
      affect the rate of change of trait means. Theoretical studies of the G-matrix
      have profitably employed simulation-based models because the topic is often too
      complex to yield meaningful analytical results. Here, we present a series of G
      matrix simulation software packages, which have emerged from about 15 years of
      research on this topic. These simulation models are useful for research and for
      building intuition regarding the evolution of the G-matrix under a wide variety
      of circumstances. A tutorial and source code also provide a foundation upon which
      future models can be built. These tools will be useful to students as well as
      researchers.

PMID- 30295863
TI  - Felt Respect for Volunteer Work and Its Associations with Volunteering Retention,
      Daily Affect, Long-term Well-being, and Mortality.
AB  - Objectives: Volunteering is associated with improved physical and psychological
      well-being; volunteers feeling more respect for their work may have better well
      being than their counterparts. Method: This study investigated the effects of
      felt respect for volunteer work on volunteering retention, daily affect, well
      being (subjective, psychological, and social), and mortality. The study analyzed
      survey and mortality data from a national sample of 2,677 volunteers from the
      Midlife in the United States Study over a 20-year span. Daily affect data were
      obtained from a sub-sample of 1,032 volunteers. Results: Compared to volunteers
      feeling less respect from others, those feeling more respect (a) were more likely
      to continue volunteering 10 and 20 years later, (b) had higher levels of daily
      positive affect and lower levels of daily negative affect, and (c) had higher
      levels of well-being over a 20-year period. The effect of felt respect on
      mortality was not statistically significant. Discussion: Greater level of felt
      respect for volunteer work is positively related to volunteers' retention rates,
      daily affective experience, and well-being.

PMID- 30295864
TI  - BIGGER ORGANS and ELEPHANT EAR-LIKE LEAF1 control organ size and floral organ
      internal asymmetry in pea (Pisum sativum L.).
AB  - Control of organ size and shape by cell proliferation and cell expansion is a
      fundamental process during plant development, but the molecular mechanisms that
      set the final size and shape of determinate organs in plants remain unclear,
      especially in legumes. In this study, we characterized several mutants including
      bigger organs (bio) and elephant-ear-like leaf 1 (ele1) in pea that displayed
      similar phenotypes, with the enlarged leaves and symmetrical lateral and ventral
      petals. Genetic analysis showed that BIO interacted with specific regulators
      SYMMETRICAL PETAL1 (SYP1) and SYP5 to control floral organ internal (IN)
      asymmetry in pea. Using a comparative approach, we cloned BIO and ELE1, revealing
      that they encode a KIX domain protein and an ortholog of Arabidopsis PEAPOD
      (PPD), respectively. Furthermore, genetic analysis, physical interaction assays
      and gene expression analysis showed that BIO and ELE1 physically interact with
      each other and with the transcription factor LATHYROIDES (LATH) to repress
      expression of downstream genes such as GROWTH-REGULATING-FACTOR 5. Our data
      suggested that the BIO-ELE1 module in legumes plays a key role to regulate organ
      development so as to create distinct final forms with characteristic size and
      shape.

PMID- 30295865
TI  - Letter: Complications of Head Immobilization Devices in Children: Contact
      Mechanics, and Analysis of a Single Institutional Experience.

PMID- 30295868
TI  - Acetoin and 2,3-butanediol from Bacillus amyloliquefaciens induce stomatal
      closure in Arabidopsis thaliana and Nicotiana benthamiana.
AB  - Plants live in close association with large communities of microbes, some of
      which are foliar pathogens that invade tissues, primarily via stomata on the leaf
      surface. Stomata are considered part of an integral, innate immunity system
      capable of efficiently preventing pathogens from entering the host plant.
      Although Bacillus, a typical plant growth-promoting rhizobacterium, is known to
      induce stomatal closure, the substances participating in this closure and the
      mechanism involved in its regulation remain poorly understood. Here, we screened
      a mutant library and conducted site-specific mutagenesis experiments in order to
      identify such substances. We found that acetoin and 2,3-butanediol from B.
      amyloliquefaciens FZB42 induced stomatal closure in Arabidopsis thaliana and
      Nicotiana benthamiana. These two components could function either via root
      absorption or volatilization to restrict stomatal apertures, but root absorption
      was more efficient. Both substances invoked the salicylic acid and abscisic acid
      signaling pathways to close the stomata and stimulated accumulation of hydrogen
      peroxide and nitric oxide. The results present comprehensive evidence of how soil
      rhizobacteria may affect plant stomata, in a way that reinforces the evolved
      mutualism between the two groups of organisms, and provide potential alternative
      avenues of research towards reducing the incidence of disease in crops.

PMID- 30295867
TI  - Clinical Features and Genotypes of Patients with Hemoglobin H Disease in Taiwan.
AB  - Background: The genetic background of patients with hemoglobin (Hb) H disease in
      Taiwan has been investigated; however, the clinical features and treatment
      outcomes were not reported. Objective: To analyze the clinical features and
      genotypes of patients with HbH who reside in Taiwan. Methods: We conducted a
      retrospective analysis of the clinical and molecular characteristics of 38
      patients with HbH disease who were undergoing treatment at Kaohsiung Medical
      University Hospital, Taiwan. Results: Initial Hb levels were lower and the
      numbers of patients requiring iron-chelation therapy were higher in the
      nondeletional HbH group than in the deletional HbH group (P <.05). Compared with
      the healthy population, the patients with HbH disease exhibited short body
      length, low body weight, and low body mass index (BMI). Conclusions: Patients
      with nondeletional HbH disease had lower Hb levels and a higher requirement for
      splenectomy and iron-chelation therapy than did those with deletional HbH
      disease. Also, growth status was compromised in patients with HbH disease.

PMID- 30295866
TI  - Understanding the Factors That Shape Patterns of Nucleotide Diversity in the
      House Mouse Genome.
AB  - A major goal of population genetics has been to determine the extent by which
      selection at linked sites influences patterns of neutral nucleotide diversity in
      the genome. Multiple lines of evidence suggest that diversity is influenced by
      both positive and negative selection. For example, in many species there are
      troughs in diversity surrounding functional genomic elements, consistent with the
      action of either background selection (BGS) or selective sweeps. In this study,
      we investigated the causes of the diversity troughs that are observed in the wild
      house mouse genome. Using the unfolded site frequency spectrum, we estimated the
      strength and frequencies of deleterious and advantageous mutations occurring in
      different functional elements in the genome. We then used these estimates to
      parameterize forward-in-time simulations of chromosomes, using realistic
      distributions of functional elements and recombination rate variation in order to
      determine whether selection at linked sites can explain the observed patterns of
      nucleotide diversity. The simulations suggest that BGS alone cannot explain the
      dips in diversity around either exons or conserved noncoding elements. A
      combination of BGS and selective sweeps produces deeper dips in diversity than
      BGS alone, but the inferred parameters of selection cannot fully explain the
      patterns observed in the genome. Our results provide evidence of sweeps shaping
      patterns of nucleotide diversity across the mouse genome and also suggest that
      infrequent, strongly advantageous mutations play an important role in this. The
      limitations of using the unfolded site frequency spectrum for inferring the
      frequency and effects of advantageous mutations are discussed.

PMID- 30295869
TI  - Who can decide? Prevalence of mental incapacity for treatment decisions in
      medical and surgical hospital inpatients in Ireland.
AB  - Background: The prevalence of mental incapacity for treatment decisions among
      medical and surgical hospital inpatients is poorly understood or not known in
      many countries, including Ireland. Aim: To assess the prevalence of mental
      incapacity in hospital inpatients in Ireland. Design: Cross-sectional
      observational study of mental incapacity for treatment decisions. Methods: We
      assessed mental capacity in 300 randomly selected hospital inpatients in 2
      general hospitals in Dublin (urban) and Portlaoise (rural), in Ireland, using the
      MacArthur Competence Assessment Tool for Treatment (MacCAT-T). Results: Mean
      MacCAT-T score was 14.80 (SD: 8.40) out of a possible maximum of 20 (with a
      higher score indicating greater mental capacity). Over one quarter of
      participants (27.7%; n = 83) lacked the mental capacity for treatment decisions;
      1.7% (n = 5) had partial capacity and 70.7% (n = 212) had full capacity. Scores
      for each of the four sub-scales of the MacCAT-T were generally consistent across
      the four key areas of understanding, appreciation, reasoning and expressing a
      choice. Conclusions: Mental incapacity for treatment decisions is common in
      medical and surgical hospital inpatients in Ireland. This issue both merits and
      requires greater attention in clinical practice, research and legislation.

PMID- 30295870
TI  - The NASSAU (New ASSessment of cerebral Arteriovenous Malformations yet
      Unruptured) Analysis: Are the Results From The ARUBA Trial Also Applicable to
      Unruptured Arteriovenous Malformations Deemed Suitable for Gamma Knife Surgery?
AB  - BACKGROUND: The optimal management of unruptured brain arteriovenous
      malformations (AVMs) is controversial after the ARUBA trial. OBJECTIVE: To
      confirm or repudiate the ARUBA conclusion that "medical management only is
      superior to medical management with interventional therapy for unruptured brain
      arteriovenous malformations." METHODS: Data were collected from 1351 patients
      treated with Gamma Knife Surgery (GKS; Elekta AB, Stockholm, Sweden) for
      unruptured and untreated AVMs The follow-up was 8817 yr (median 5.0 and mean
      6.5). The results of the analyses were compared to that found in patients
      randomized to medical management only in the ARUBA trial and extrapolated to a 10
      yr time period. Our data were also compared to the natural course in a virtual
      AVM population for a 25-yr time period. RESULTS: The incidence of stroke was
      similar among ARUBA and our patients for the first 5 yr. Thereafter, the longer
      the follow-up, the relatively better outcome following treatment. Both the
      mortality rate and the incidence of permanent deficits in patients with small
      AVMs were the same as in untreated patients for the first 2 to 3 yr after GKS,
      after which GKS patients did better. Patients with large AVMs had a higher
      incidence of neurological deficits in the first 3 yr following GKS. The
      difference decreased thereafter, but the time until break even depended on the
      analysis method used and the assumed risk for hemorrhage in patent AVMs.
      CONCLUSION: The ARUBA trial conclusion that medical management is superior to
      medical management with interventional therapy for all unruptured AVMs could be
      repudiated.

PMID- 30295872
TI  - The apple-core sign of an ileocecal carcinoma.

PMID- 30295871
TI  - Multi-omic and multi-view clustering algorithms: review and cancer benchmark.
AB  - Recent high throughput experimental methods have been used to collect large
      biomedical omics datasets. Clustering of single omic datasets has proven
      invaluable for biological and medical research. The decreasing cost and
      development of additional high throughput methods now enable measurement of multi
      omic data. Clustering multi-omic data has the potential to reveal further systems
      level insights, but raises computational and biological challenges. Here, we
      review algorithms for multi-omics clustering, and discuss key issues in applying
      these algorithms. Our review covers methods developed specifically for omic data
      as well as generic multi-view methods developed in the machine learning community
      for joint clustering of multiple data types. In addition, using cancer data from
      TCGA, we perform an extensive benchmark spanning ten different cancer types,
      providing the first systematic comparison of leading multi-omics and multi-view
      clustering algorithms. The results highlight key issues regarding the use of
      single- versus multi-omics, the choice of clustering strategy, the power of
      generic multi-view methods and the use of approximated p-values for gauging
      solution quality. Due to the growing use of multi-omics data, we expect these
      issues to be important for future progress in the field.

PMID- 30295873
TI  - A supercomplex, approximately 720 kDa and composed of both photosystem reaction
      centers, dissipates excess energy by PSI in green macroalgae under salt stress.
AB  - The thylakoid membranes of plants play a critical role in electron transfer and
      energy fixation, and are highly dynamic. So far, studies on the thylakoid
      membranes have mainly focused on microalgae and higher plants, yet very little
      information is available on the macroalgal thylakoids. Here, we studied the
      structure and organization of the thylakoid membranes in Ulva prolifera, a
      representative species of the green macroalgae. We found U. prolifera had few but
      long loosely-stacked membranes which lack the conventional grana found in higher
      plants. However, the thylakoid membrane complexes demonstrate lateral
      heterogeneity. Moreover, we found a supercomplex composed of Photosystem II
      (PSII), light-harvesting complex II (LHCII) and Photosystem I (PSI) from U.
      prolifera under salt stress. The supercomplex is approximately 720 kDa, and
      includes the two important photoprotection proteins Photosystem II S subunit
      (PsbS) and the light-harvesting complex stress-related protein (LhcSR), as well
      as xanthophyll cycle pigments (violaxanthin, antheraxanthin and zeaxanthin). Time
      resolved fluorescence analysis suggested that, in the supercomplex, excitation
      energy could efficiently be transferred from PSII to PSI, even when PSII was
      inhibited, a function which disappeared when the supercomplex was incubated in
      mild detergent. We suggest that the supercomplex might be an important mechanism
      to dissipate excess energy by PSI in green macroalgae under salt stress.

PMID- 30295874
TI  - Commentary: Stereotactic Body Radiotherapy for Spinal Metastases at the Extreme
      ends of the Spine: Imaging-Based Outcomes for Cervical and Sacral Metastases.

PMID- 30295875
TI  - Uniformed Services University Women's Enrollment and Career Choices in Military
      Medicine: A Retrospective Descriptive Analysis.
AB  - Introduction: The purpose of this study was to examine Uniformed Services
      University (USU) women graduates in terms of percent of graduates', specialty
      choices and practice choices as compared to civilian women who graduate and
      practice medicine in the USA. This is a perspective that is currently not well
      understood. Materials and Methods: We conducted a retrospective cohort study of
      all USU women graduates (1980-2015) using the 2016 American Medical Association
      (AMA) Physician Masterfile that included data from the American Board of Medical
      Specialties (ABMS). To describe USU women graduates' current practice status we
      queried for: (1) medical school; (2) year of graduation; (3) practice state; (4)
      primary specialty board; and (5) major professional activity (office-based
      practice vs. full-time hospital staff). Data were analyzed using descriptive
      statistics. Results: Our findings indicate that the percentage of USU women
      graduates has increased over time and stands at 29% for the 2010-2015 cohort as
      compared to 48% for women graduating from all U.S. medical schools. USU women
      graduates have a slightly higher board certification rate (89%) than the national
      cohort (88%). USU women graduates also have a higher percentage in family
      medicine (19%) than the national cohort (14%). USU women graduates practice in 48
      states and were equally split between full-time hospital staff and office-based
      practice which differs from the national cohort that has a much higher proportion
      in office-based practice (85%). Conclusions: Women are making significant gains
      in enrollment at USU, obtaining board certification at similar, and in some
      cases, higher rates than their civilian peers, and practicing in diverse
      specialties. This study provides a descriptive picture of women's enrollment and
      practice characteristics from a military-based medical school. Future work could
      examine underlying factors that may influence their school choice, career
      experiences, and trajectories. Future research could also focus on women's
      experiences of mentoring and support to better understand these factors.

PMID- 30295877
TI  - Commentary: Toward Supratotal Resection of Clival Chordoma: Combined Endoscopic
      Endonasal and Contralateral Transmaxillary Approaches.

PMID- 30295876
TI  - PIKfyve accelerates phagosome acidification through activation of TRPML1 while
      arrests aberrant vacuolation independent of the Ca2+ channel.
AB  - PIKfyve phosphorylates PtdIns(3)P to PtdIns(3,5)P2. One of the best characterized
      effector downstream of PtdIns(3,5)P2 is a lysosomal Ca2+ channel, TRPML1.
      Although it has been reported that TRPML1 is involved in phagosome-lysosome
      fusion, the relevance of the Ca2+ channel in phagosome acidification has been
      denied. In this paper, however, we demonstrated that the phagosome acidification
      was dependent on TRPML1. Based on the classical idea that FITC-fluorescence is
      highly sensitive to acidic pH, we could estimate the phagosome acidification by
      time laps imaging. FITC-zymosan fluorescence that was engulfed by macrophages,
      decreased immediately after the uptake while the extinction of FITC-zymosan
      fluorescence was delayed in PIKfyve-deficient cells. The acidification arrest was
      completely rescued in the presence of Ca2+ ionophore A23187. Cells treated with a
      PIKfyve inhibitor, apilimod, also showed delayed phagosome acidification but were
      rescued by the overexpression of TRPML1. Additionally, TRPML1 agonist, ML-SA1 was
      effective to acidify the phagosome in PIKfyve-deficient cells. Another phenotype
      observed in PIKfyve-deficient cells is vacuole formation. Unexpectedly, enlarged
      vacuole formation in PIKfyve-deficient cells was not rescued by Ca2+ or over
      expression of TRPML1. It is likely that the acidification and vacuolation arrest
      is bifurcating downstream of PIKfyve.

PMID- 30295878
TI  - Combat-Related Invasive Fungal Infections: Development of a Clinically Applicable
      Clinical Decision Support System for Early Risk Stratification: Corrigendum.

PMID- 30295879
TI  - Alternatives to thrombolysis in submassive saddle pulmonary embolism.

PMID- 30295880
TI  - Microsurgical Resection of Anaplastic Ependymoma of the Cerebellopontine Angle in
      an Adult: 3-Dimensional Operative Video.
AB  - Infratentorial ependymomas usually arise in the fourth ventricle and extend into
      the cerebellopontine angle (CPA) through the foramina of Luschka is well
      described. A primary CPA location of an ependymoma is distinctly uncommon. In
      this 3-dimensional video, we present a 38-yr-old woman with a 1-mo history of
      vertigo and slow left sided gaze drift. She underwent microsurgical gross total
      resection of the CPA ependymoma via retrosigmoid approach. The histopathology was
      grade III anaplastic ependymoma. She tolerated the surgery well and her
      postoperative course was uneventful. She received radiation therapy and there was
      no recurrent disease in follow-up studies. Important steps of the surgical
      approach and microsurgical techniques in resection of these challenging tumors
      are demonstrated in this 3-dimensional surgical video. The patient consented to
      publication of her image.

PMID- 30295881
TI  - Synergistic combinations of azoles and antihistamines against Candida species in
      vitro.
AB  - Fungal infections are a major cause of skin and mucosal membrane disease.
      Immunocompromised individuals, such as those undergoing chemotherapy, are most
      susceptible to fungal infections. With a growing population of immunocompromised
      patients, there are many reports of increasing numbers of infections and of
      fungal strains resistant to current antifungals. One way to treat drug-resistant
      infections is to administer combinations of drugs to patients. Azoles are the
      most prescribed antifungals, as they are broad-spectrum and orally bioavailable.
      Terfenadine (TERF) and ebastine (EBA) are second-generation antihistamines, with
      EBA being used in many countries. In this study, we explored combinations of
      seven azole antifungals and two antihistamines (TERF and EBA) against a panel of
      13 Candida fungal strains. We found 55 out of 91 combinations tested of TERF and
      EBA against the various fungal strains to be synergistic with the azoles. To
      evaluate the efficiency of these combinations to inhibit fungal growth, we
      performed time-kill assays. We also investigated the ability of these
      combinations to disrupt biofilm formation. Finally, we tested the specificity of
      the combinations towards fungal cells by mammalian cytotoxicity assays. These
      findings suggest a potential new strategy for targeting drug-resistant Candida
      infections.

PMID- 30295882
TI  - Resection of an Embolized Cirsoid Aneurysm With Intracranial Venous Drainage: 2
      Dimensional Operative Video.
AB  - Cirsoid aneurysms, also known as scalp arteriovenous malformations (AVM), are
      rare congenital extracranial vascular anomalies that often present as an
      enlarging pulsatile scalp mass. A 14-yr-old male presented with a pulsatile scalp
      lesion that was first noticed 3 yr prior and had progressively enlarged. No
      history of trauma was reported. MRI demonstrated a 4 cm wide and 2 cm tall nidus
      and catheter angiography was performed to further define the vascular supply and
      drainage. The patient underwent transvenous endovascular embolization followed by
      surgical excision via a bicoronal incision, as shown in this operative video.
      Care was taken to identify, cauterize, and transect feeding vessels from the
      superficial temporal, supratrochlear, and supraorbital arteries circumferentially
      to completely devascularize and resect the galeal nidus from overlying scalp
      tissue and underlying pericranium. Previously unreported in the literature,
      transosseous emissary veins partially draining the lesion were noted on
      angiography and were waxed thoroughly during surgery. Six-month follow-up
      examination demonstrated a well-healed incision without evidence of AVM
      recurrence. The unique venous drainage of this cirsoid aneurysm highlights the
      value of diagnostic angiography to fully characterize these rare and complex
      vascular lesions prior to pursuing definitive treatment. IRB approval was
      obtained from the Ann & Robert H. Lurie Children's Hospital of Chicago
      Institutional Review Board (IRB #2018-1799). The IRB waives the requirement of
      obtaining informed consent for this study in accordance with 45 CFR 46.116(d).

PMID- 30295883
TI  - Cost and Healthcare Utilization Among Non-Elderly Head and Neck Cancer Patients
      in the Military Health System, a Single-Payer Universal Health Care Model.
AB  - Introduction: Examining costs and utilization in a single-payer universal health
      care system provides information on fiscal and resource burdens associated with
      head and neck cancer (HNC). Here, we examine trends in the Department of Defense
      (DoD) HNC population with respect to: (1) reimbursed annual costs and (2)
      patterns and predictors of health care utilization in military only, civilian
      only, and both systems of care (mixed model). Materials and Methods: A
      retrospective, cross-sectional study was conducted using TRICARE claims data from
      fiscal years 2007 through 2014 for reimbursement of ambulatory, inpatient, and
      pharmacy charges. The study was approved by the Defense Health Agency Office of
      Privacy and Civil Liberties as exempt from institutional review board full
      review. The population was all beneficiaries, age 18-64, with a primary ICD-9
      diagnosis of HNC, on average, 2,944 HNC cases per year. The outcomes of
      regression models were total reimbursed health care cost, and counts of
      ambulatory visits, hospitalizations, and bed days. The predictors were fiscal
      year, demographic variables, hospice use, type and geographic region of TRICARE
      enrollment, use of military or civilian care or mixed use, cancer treatment
      modalities, the number of physical and mental health comorbid conditions, and
      tobacco use. A priori, null hypotheses were assumed. Results: Per annual average,
      61% of the HNC population was age 55-64, and 69% were males. About 6% accessed
      military facilities only for all health care, 60% accessed civilian only, and 34%
      accessed both military and civilian facilities. Patients who only accessed
      military care had earlier stage disease as indicated by rates of single modality
      treatment and hospice use; military care only and mixed use had similar rates of
      combination treatment and hospice use. The average cost per patient per year was
      $14,050 for civilian care only, $13,036 for military care only, and $29,338 for
      mixed use of both systems. The strongest predictors of higher cost were
      chemotherapy, radiation therapy, head and neck surgery, hospice care, and mixed
      use care. The strongest predictors of health care utilization were chemotherapy,
      use of hospice, the number of physical and mental health comorbidities, radiation
      therapy, head and neck surgery, and system of care. Conclusions: To a single
      payer, the use of a single system of care exclusively among HNC patients is more
      cost-effective than use of a mixed-use system. The results suggest an over
      utilization of ambulatory care services when both military and civilian care are
      accessed. Further investigation is needed to assess coordination between systems
      of care and improved efficiencies with respect to the cost and apparent over
      utilization of health care services.

PMID- 30295884
TI  - Needlestick injuries among Malaysian healthcare workers.
AB  - Background: Needlestick injury (NSI) is a significant occupational health issue
      among healthcare workers (HCWs). Aims: To determine the national self-reported
      incidence and risk factors for NSI among Malaysian Ministry of Health (MOH) HCWs.
      Methods: Using data from the MOH national sharps injury surveillance programme,
      information on reported NSIs over a 1-year period (2016) for different HCW
      subgroups were extracted and analysed. Results: A total of 1234 NSI cases were
      reported in 2016, giving an overall incidence of 6 injuries per 1000 HCWs.
      Medical doctors recorded the highest incidence (21.1 per 1000 HCWs) followed by
      dental staff (7.5), pharmacy staff (4.2), nurses (3.7), medical assistants (3.4)
      and allied and auxiliary staff (1.0). Doctors had significantly increased risk of
      NSI compared with allied and auxiliary staff (relative risk [RR] = 20.7, 95%
      confidence interval [CI] 15.5-27.5), medical assistants (RR = 6.1, 95% CI 4.5
      8.2), nurses (RR = 5.7, 95% CI 5.0-6.6), pharmacy staff (RR = 5.0, 95% CI 3.7
      6.6) and dental staff (RR = 2.8, 95% CI 2.2-3.5). Significant differences were
      found in age and sharps- handling experience between occupational subgroups (P <
      0.001 for both variables). Male employees had higher risk than females (RR =
      1.33, 95% CI 1.18-1.50), with a significant difference seen in their sharps
      handling experience (P < 0.01). Important risk factors included unsafe practices
      such as recapping of needles and their improper disposal. Conclusions: The
      national incidence of NSI amongst Malaysian HCWs was lower compared with other
      countries, but unsafe practices remain an important concern. There is a need to
      formulate, implement and monitor safe and consistent practices for the different
      healthcare professionals.

PMID- 30295885
TI  - Measles immunity in an Italian teaching hospital.
AB  - Background: Healthcare workers (HCWs) have an increased exposure risk to measles,
      which can put them, their patients and their relatives at risk of infection. In
      Italy, 4617 cases of measles were reported in 2017; 302 involving HCWs. According
      to the Italian National Immunization and Prevention Plan, all HCWs should have
      demonstrable evidence of immunity to measles. Aims: To evaluate measles
      immunization status in HCWs at a large Italian teaching hospital. Methods: We
      analysed clinical records and measles-specific IgG antibody titres of HCWs
      undergoing occupational health surveillance between 1 January and 31 August 2017.
      Results: Among the 1532 HCWs (mean age 32.7 +/- 10.4 years) included in the
      study, 87% (1328) had protective antibody titres. The proportion of protective
      titres was highest in those born before 1982. No significant gender differences
      in mean measles-specific IgG antibody titres were detected. Conclusions: Our
      study shows non-protective measles IgG antibody titres in a substantial
      percentage of HCWs, especially those born in the 1980s and 1990s. Due to the
      increased risk of measles transmission in the hospital environment, increased
      prevention strategies are required, including rigorous screening and prompt
      vaccination of non-immune workers.

PMID- 30295886
TI  - The spatiotemporal deposition of lysophosphatidylcholine within starch granules
      of maize endosperm and its relationships to the expression of genes involved in
      endoplasmic reticulum-amyloplast lipid trafficking and galactolipid synthesis.
AB  - The presence of lipids within starch granules is specific to cereal endosperm
      starches. These starch lipids are composed of lysophospholipids, especially
      lysophosphatidylcholine (LysoPC) and free fatty acids that strongly impact the
      assembly and properties of cereal starches. However, the molecular mechanisms
      associated with this specific lipid routing have never been investigated. In this
      study, MALDI mass spectrometry imaging revealed decreasing gradients in starch
      LysoPC concentrations from the periphery to the center of developing maize
      endosperms. This spatiotemporal deposition of starch LysoPC was similar to the
      one previously observed for ER-synthesized storage proteins, i.e., zeins,
      suggesting that LysoPC might originate in the ER, as already reported for
      chloroplasts. Furthermore, a decrease of the palmitate concentration of
      amyloplast galactolipids was observed during endosperm development, correlated
      with the preferential trapping of palmitoyl-LysoPC by starch carbohydrates,
      suggesting a link between LysoPC and galactolipid synthesis. Using microarray,
      the homologous genes of the Arabidopsis ER-chloroplast lipid trafficking and
      galactolipid synthesis pathways were also expressed in maize endosperm. These
      strong similarities suggest that the encoded enzymes and transporters are adapted
      to managing the differences between chloroplast and amyloplast lipid homeostasis.
      Altogether, our results led us to propose a model where ER-amyloplast lipid
      trafficking directs the LysoPC towards one of two routes, the first towards the
      stroma and starch granules and the other towards galactolipid synthesis.

PMID- 30295887
TI  - Response to "Alternatives to thrombolysis in submassive saddle pulmonary
      embolism".

PMID- 30295888
TI  - Secondary pulmonary alveolar proteinosis in acute myeloid leukemia.

PMID- 30295889
TI  - Microsurgery of Spinal Dural Arteriovenous Fistula Using Indocyanine Green Video
      Angiography: 2-Dimensional Operative Video.
AB  - Spinal dural arteriovenous fistulas (SDAVF) develop by direct abnormal
      arteriovenous connection between both sides of the spinal dura matter. In this
      condition, there is no intervening nidus between a meningeal segmental artery and
      a radiculomedullary vein. Open microsurgery is one of the choices for patients
      with SDAVF. When the AVF is on the inner dural surface, we can easily block the
      radiculomedullary vein in a microscopic view. We herein report a 50-yr-old woman
      who presented with low back pain, was diagnosed with an SDAVF, and underwent
      surgical treatment under a microscopic view. The spinal angiography demonstrated
      abnormal arteriovenous connections between intercostal arteries at the level of
      Th11 to 12 and the intradural radiculomedullary vein. Operative indocyanine green
      (ICG) microangiography demonstrated the blood flow in meningeal vessels and their
      anastomoses between both sides of the dural surface. We easily identified the
      radiculomedullary vein fed by the surrounding meningeal feeding arteries and
      block completely under a direct microscopic view. We detected the change in
      hemodynamic during feeder ligation by Flow 800 (Zeiss Penteto Flow 800
      microscope; Zeiss Corporation, Tokyo, Japan). After surgery, the patient's
      symptoms disappeared and no recurrence of the disease has been noted in the past
      23 mo. We have received the informed consent of this patient for the publication
      of this case report.

PMID- 30295890
TI  - A Tale of Two Compulsions - Two Case Studies Using Accelerated Resolution Therapy
      (ART) for Obsessive Compulsive Disorder (OCD).
AB  - Although research for accelerated resolution therapy (ART) has been predominately
      for post-traumatic stress disorder, ART has shown promise as a treatment for
      other behavioral health conditions as well. ART is a brief, trauma-focused, eye
      movement-based therapy that has been successfully utilized to treat a wide array
      of behavioral health disorders, including obsessive compulsive disorder. This
      article will present an overview of the theory behind the reconsolidation concept
      used in ART and two cases of obsessive compulsive disorder treatment using ART
      with outcome measures visual trend analysis.

PMID- 30295891
TI  - Misidentification of Burkholderia pseudomallei as Acinetobacter species in
      northern Thailand.
AB  - Background: Burkholderia pseudomallei is the causative agent of melioidosis, a
      disease endemic throughout the tropics. Methods: A study of reported
      Acinetobacter spp. bacteraemia was performed at Chiang Rai provincial hospital
      from 2014 to 2015. Isolates were collected and tested for confirmation. Results:
      A total of 419 putative Acinetobacter spp. isolates from 412 patients were re
      identified and 5/419 (1.2%) were identified as B. pseudomallei. Four of the five
      patients with melioidosis died. An estimated 88/419 (21%) isolates were correctly
      identified as Acinetobacter spp. Conclusions: Misidentification of Acinetobacter
      spp. as B. pseudomallei or other bacteria is not uncommon and programmes to
      address these shortfalls are urgently required.

PMID- 30295892
TI  - Functional conservation of a developmental switch in mammals since the Jurassic
      age.
AB  - ThPOK is a "master regulator" of T lymphocyte lineage choice, whose presence or
      absence is sufficient to dictate development to the CD4 or CD8 lineages,
      respectively. Induction of ThPOK is critically regulated at the transcriptional
      level, via a lineage-specific silencer element, SilThPOK. Here, we take advantage
      of the available genome sequence data as well as site-specific gene targeting
      technology, to evaluate the functional conservation of ThPOK regulation across
      mammalian evolution, and assess the importance of motif grammar (order and
      orientation of TF binding sites) on SilThPOK function in vivo. We make 3
      important points: First, the SilThPOK is present in marsupial and placental
      mammals, but is not found in available genome assemblies of non-mammalian
      vertebrates, indicating that it arose after divergence of mammals from other
      vertebrates. Secondly, by replacing the murine SilThPOK in situ with its
      marsupial equivalent using a knockin approach, we demonstrate that the marsupial
      SilThPOK supports correct CD4 T lymphocyte lineage-specification in mice. To our
      knowledge, this is the first in vivo demonstration of functional equivalency for
      a silencer element between marsupial and placental mammals using a definitive
      knockin approach. Finally, we show that alteration of the position/orientation of
      a highly conserved region within the murine SilThPOK is sufficient to destroy
      silencer activity in vivo, demonstrating that motif grammar of this "solid"
      synteny block is critical for silencer function. Dependence of SilThPOK function
      on motif grammar conserved since the mid-Jurassic age, 165 million years ago,
      suggests that the SilThPOK operates as a silenceosome, by analogy with the
      previously proposed enhanceosome model.

PMID- 30295893
TI  - Endoplasmic Reticulum (ER) Membrane Proteins (LUNAPARKs) are Required for Proper
      Configuration of the Cortical ER Network in Plant Cells.

PMID- 30295895
TI  - Organizing Pneumonia in a Patient with Rheumatoid Arthritis with Progression to
      Usual Interstitial Pneumonia.

PMID- 30295896
TI  - Corrigendum.

PMID- 30295894
TI  - A Pilot Comparison of Multispectral Fluorescence to Indocyanine Green
      Videoangiography and Other Modalities for Intraoperative Assessment in Vascular
      Neurosurgery.
AB  - BACKGROUND: Digital subtraction angiography (DSA) is the gold standard for
      vascular imaging, but is not easily integrated into a continuous microsurgical
      environment. Other available modalities for intraoperative vascular assessment
      have their own limitations. OBJECTIVE: To investigate multispectral fluorescence
      (MFL), a new technology based on indocyanine green (ICG) fluorescence, which may
      provide advantages over current intraoperative imaging modalities. METHODS:
      Cadaveric intracranial aneurysm models and turkey wing bypasses were created and
      tested with white light and micro-Doppler ultrasound, indocyanine green
      videoangiography (ICG-VA), MFL, and DSA in conditions mimicking surgery.
      Assessments with these modalities were scored by 7 neurosurgeons. RESULTS: DSA
      was significantly better than other modalities in evaluating the vasculature (P <
      .0001), but was significantly less ergonomic and efficient (P < .0001). MFL and
      ICG-VA were not significantly different from each other. Both were significantly
      better than white light/micro-Doppler ultrasound in assessing occlusion and
      patency (P <= .011), and both were better than DSA in ergonomics and efficiency
      (P < .0001). CONCLUSION: MFL performs similarly to ICG-VA in a laboratory
      setting. Further study will be required to determine whether it compares
      favorably in the operating room. While DSA is the standard for cerebrovascular
      visualization, MFL and ICG are significantly more ergonomic and efficient.

PMID- 30295897
TI  - Prenatal bisphenol A exposure alters epithelial cell composition in the rhesus
      macaque fetal oviduct.
AB  - Bisphenol A (BPA) is an endocrine disrupting compound that is a pervasive
      environmental contaminant. Although it has been reported to affect the
      development of a variety of fetal reproductive tissues, data on the effect of
      fetal BPA exposure on oviducts were extremely limited and were only available in
      mice. To determine if there are adverse effects of gestational BPA exposure on
      fetal oviduct, we exposed pregnant rhesus macaques with female fetuses to oral or
      non-oral BPA during the last trimester of gestation (day 100 to term). After the
      treatment, fetal oviducts were collected for morphology evaluation. BPA exposure
      altered the percentages of different cell types (ciliated, non-ciliated, and
      secretory) in the fetal oviduct and resulted in a significant high ciliated cell
      population in the BPA-exposed fetal oviduct. The distribution of ciliated cells
      on the epithelium in the BPA-exposed fetal oviduct was also altered. Gestational
      BPA exposure reduced the expression of mucosubstance and uteroglobin in secretory
      cells in the fetal oviduct. A comparison of the outcome of the fetal oviduct
      studies with similar outcomes previously reported in the lung from the same
      fetuses demonstrates that BPA exhibits opposite effects in these two organs. In
      conclusion, the BPA-associated alterations in the fetal oviduct could potentially
      affect the oviduct morphology and function later in life with a negative impact
      fertility. The mechanisms of action of the differential response of the oviduct
      and lung to BPA exposure require further investigation.

PMID- 30295898
TI  - Variation in ICE1 Methylation Primarily Determines Phenotypic Variation in
      Freezing Tolerance in Arabidopsis Thaliana.
AB  - Cold stress is a major abiotic factor plants face during their life cycle.
      Although plants often exhibit phenotypic variation in cold tolerance, the
      underlying mechanism remains poorly understood. In the present study, the 50%
      lethal temperature (LT50) values of 37 Arabidopsis thaliana accessions at
      latitudes from 15 degrees  to 58 degrees  ranged from -13.2  degrees C to -4.9 
      degrees C and were closely correlated with the cold climates of the collection
      sites. According to a methylation analysis of all C-repeat (CRT)-binding factor
      (CBF) pathway genes, the coding and promoter regions of AtICE1, a regulator of
      CBF genes, exhibited the greatest variability in methylation levels among the
      accessions and included 5 to 122 methylated cytosine residues. In contrast,
      unmethylated or only slightly methylated genes in the CBF pathway showed little
      variation among the accessions. According to a gene expression analysis of four
      selected A. thaliana populations with distinct methylation patterns, except for
      the downregulated gene AtCBF2, the expression levels of all members of the CBF
      pathway were negatively correlated with AtICE1 gene methylation levels. Treatment
      of the four A. thaliana populations with the DNA methylation inhibitory reagent 5
      azacytidine resulted in a 30.0-78.3% enhancement of freezing tolerance and
      decreases in LT50 values of approximately 1.9-3.6  degrees C. Similar effects
      were observed in drm2 mutants, including 30.0-48.3% increases in freezing
      tolerance and decreases in LT50 values of approximately 0.7-3.4  degrees C. Thus,
      the AtICE1 methylation-regulated transcription of CBF pathway genes is
      responsible for the phenotypic variation in the freezing tolerance observed in A.
      thaliana.

PMID- 30295899
TI  - Isolation and characterization of Chlamydomonas autophagy-related mutants in
      nutrient-deficient conditions.
AB  - Autophagy is a recycling system for amino acids and carbon- and nitrogen (N)
      containing compounds. To date, the functional importance of autophagy in
      microalgae in nutrient-deficient conditions has not been evaluated by using
      autophagy-defected mutants. Here, we provide a series of evidence which support
      the following notions by characterizing an insertional mutant of the autophagy
      related gene ATG8, encoding a ubiquitin-like protein necessary for the formation
      of the autophagosome in the green alga, Chlamydomonas reinhardtii. First, ATG8 is
      required for maintenance of cell survival and chlorophyll content in the N-,
      sulfur-, and phosphate-deficient conditions. Second, ATG8 supports the
      degradation of triacylglycerol and lipid droplets after the resupply of N to
      cells cultured in N-limiting conditions. Third, ATG8 is also necessary for
      accumulation of starch in phosphate-deficient conditions. Additionally, autophagy
      is not essential for maternal inheritance of the organelle genomes in
      gametogenesis.

PMID- 30295900
TI  - Paramedian Supracerebellar Approach in Semi-Sitting Position for Endoscopic
      Resection of Pineal Cyst: 2-Dimensional Operative Video.
AB  - In this video, we present the case of a 41-yr-old female with new onset of
      recurrent syncopal episodes. She underwent extensive evaluations and diagnostic
      work-up by cardiology and neurology, excluding any other cause than a large
      pineal cyst that was found on magnetic resonance imaging. Surgical indications
      for pineal cyst resection are very limited as most pineal cyst can be treated
      conservatively. Recurrent drop-attacks (without loss of consciousness) or
      syncopal episodes (with brief loss of consciousness) have been associated with
      pineal cysts secondary to a possible ball valve effect with shift of position
      causing sudden obstruction of the ventricular system followed by rapid rising of
      intracranial pressure. Several approaches, different positions, and alternative
      surgical techniques (microscopic vs endoscopic) have been proposed for resection
      of pineal region lesions. The semi-sitting position provides excellent exposure
      of the pineal region secondary to gravity-based retraction of the cerebellum, and
      carries minimal risk of air venous embolism when head elevation is reduced to 30
      degrees  and lower extremities are elevated. The paramedian supracerebellar
      approach is less invasive and faster than midline supracerebellar approach,
      because it requires exposure of just 1 transverse sinus (nondominant for centered
      lesions) and avoids exposure of the torcula. The endoscopic technique greatly
      improves the ergonomics of the approach when compared to the microscope based
      technique, and provides excellent visualization of all the neurovascular
      structures in the pineal region. Surgical resection was successfully performed
      with no complications and complete cyst resection. Patient was discharged on
      postoperative day 1 and remains free of syncopal episodes. The patient signed
      informed consent including the use of photographic and video material for
      educational or academic purposes.

PMID- 30295901
TI  - Spatial analysis of dengue, cysticercosis and Chagas disease mortality in
      Ecuador, 2011-2016.
AB  - Background: Neglected tropical diseases (NTDs) continue to be an important cause
      of disability and mortality in the poorest tropical and subtropical areas.
      Methods: This is an ecological study. We included all death certificates with
      dengue, cysticercosis and Chagas disease in Ecuador from 2011 to 2016. The
      spatial autocorrelation was evaluated by GeoDa software through the Global
      Moran's I index and the formation of clusters by the local index of spatial
      association. Results: The Global Moran's I index for the study period shows a
      positive spatial autocorrelation for dengue, cysticercosis and Chagas disease
      (0.25, p=0.001; 0.07, p=0.04; 0.45, p=0.001, respectively). Conclusions: The
      clusters identified as higher risk in the country could be targeted by
      policymakers to adequately develop strategies to strengthen health promotion
      policies that break the cycle of these diseases.

PMID- 30295902
TI  - Implantation of a Thoracic Spinal Cord Stimulator Paddle Electrode and Generator
      Under General Anesthesia With Intraoperative Neuromonitoring: 2-Dimensional
      Operative Video.
AB  - Spinal cord stimulation is a well-established and effective therapy in the
      treatment of pain. Proper patient selection and accurate lead placement are
      paramount in its success. Placement is a multifaceted process requiring proper
      paddle placement, a well thought out generator placement and appropriate means to
      limit complications and enhance success. Several intraoperative techniques
      maximize outcomes, including removal of the superior portion of the inferior
      level's spinous process for paddle access into the epidural space, generator
      pocket placement in a location that limits patient discomfort, a strain relief
      loop at the thoracic incision to prevent lead fractures and allow for full spinal
      flexibility, generator placement parallel to the body and secured in the pocket
      to prevent unwanted movement, and intraoperative neuromonitoring for patient
      comfort and more accurate lead placement compared to X-ray alone or awake
      placement. This case demonstrates these key elements of intraoperative technique
      in a candidate with the most common indication for spinal cord stimulator
      placement-postlaminectomy syndrome-underscoring the ease and viability of this
      procedure in the appropriate patient population in a means that reduces future
      complications and adverse events while maximizing success. Full patient consent
      for video-recording and subsequent use for research purposes was attained. All
      patient identifiers have been removed for the purpose of patient confidentiality.

PMID- 30295903
TI  - A SOC1-like gene MtSOC1a promotes flowering and primary stem elongation in
      Medicago.
AB  - Medicago flowering, like that of Arabidopsis, is promoted by vernalization and
      long days, but alternative mechanisms are predicted because Medicago lacks the
      key regulators CO and FLC. Three Medicago SOC1-like genes, including MtSOC1a,
      were previously implicated in flowering control, but no legume soc1 mutants with
      altered flowering were reported. Here, reverse transciption-quantitative PCR (RT
      qPCR) indicated that the timing and magnitude of MtSOC1a expression was regulated
      by the flowering promoter FTa1, while in situ hybridization indicated that
      MtSOC1a expression increased in the shoot apical meristem during the floral
      transition. A Mtsoc1a mutant showed delayed flowering and short primary stems.
      Overexpression of MtSOC1a partially rescued the flowering of Mtsoc1a, but caused
      a dramatic increase in primary stem height, well before the transition to
      flowering. Internode cell length correlated with stem height, indicating that
      MtSOC1a promotes cell elongation in the primary stem. However, application of
      gibberellin (GA3) caused stem elongation in both the wild type and Mtsoc1a,
      indicating that the mutant was not defective in gibberellin responsiveness. These
      results indicate that MtSOC1a may function as a floral integrator gene and
      promotes primary stem elongation. Overall, this study suggests that apart from
      some conservation with the Arabidopsis flowering network, MtSOC1a has a novel
      role in regulating aspects of shoot architecture.

PMID- 30295904
TI  - Greater lateral root branching density in maize improves phosphorus acquisition
      from low phosphorus soil.
AB  - The development of crops with better growth under suboptimal phosphorus
      availability would improve food security in developing countries while reducing
      environmental pollution in developed countries. We tested the hypothesis that
      maize (Zea mays) phenotypes with greater lateral root branching density have
      greater phosphorus acquisition from low phosphorus soils. Recombinant inbred
      lines with either 'many short' (MS) or 'few long' (FL) lateral root phenotypes
      were grown under high and low phosphorus conditions in greenhouse mesocosms and
      in the field. Under low phosphorus in mesocosms, lines with the MS phenotype had
      89% greater phosphorus acquisition and 48% more shoot biomass than FL lines.
      Under low phosphorus in the field, MS lines had 16% shallower rooting depth
      (D95), 81% greater root length density in the top 20 cm of the soil, 49% greater
      shoot phosphorus content, 12% greater leaf photosynthesis, 19% greater shoot
      biomass, and 14% greater grain yield than FL lines. These results are consistent
      with the hypothesis that the phenotype of many, shorter lateral roots improves
      phosphorus acquisition under low phosphorus availability and merits consideration
      for genetic improvement of phosphorus efficiency in maize and other crops.

PMID- 30295906
TI  - Automated morphological feature assessment for zebrafish embryo developmental
      toxicity screens.
AB  - Detection of developmental phenotypes in zebrafish embryos typically involves a
      visual assessment and scoring of morphological features by an individual
      researcher. Subjective scoring could impact results and be of particular concern
      when phenotypic effect patterns are also used as a diagnostic tool to classify
      compounds. Here we introduce a quantitative morphometric approach based on image
      analysis of zebrafish embryos. A software called FishInspector was developed to
      detect morphological features from images collected using an automated system to
      position zebrafish embryos. The analysis was verified and compared with visual
      assessments of three participating laboratories using three known developmental
      toxicants (methotrexate, dexamethasone and topiramate) and two negative compounds
      (loratadine and glibenclamide). The quantitative approach exhibited higher
      sensitivity and made it possible to compare patterns of effects with the
      potential to establish a grouping and classification of developmental toxicants.
      Our approach improves the robustness of phenotype scoring and reliability of
      assay performance and, hence, is anticipated to improve the predictivity of
      developmental toxicity screening using the zebrafish embryo.

PMID- 30295907
TI  - Left Pan-Hippocampal Low Grade Glioma-2-Stage Transsylvian Transventricular and
      Paramedian Supracerebellar Transtentorial Approaches: 2-Dimensional Operative
      Video.
AB  - The surgical goal for low-grade gliomas (LGGs) is to maximize resection while
      minimizing morbidity. Pan-hippocampal LGGs extend from the hippocampal head to
      the hippocampal tail, and involve the parahippocampal gyrus and uncus. Given
      their anteroposterior extension, they cannot be completely removed with 1 single
      approach, requiring a 2-stage front-to-back operation. In this video, we present
      the case of a 52-yr-old man with new onset of generalized seizures and a dominant
      side, nonenhancing, pan-hippocampal infiltrative lesion compatible with a low
      grade glioma. Preoperative high-definition fiber tractography (HDFT) showed the
      spatial relationship of the tumor with surrounding fiber tracts, such as the
      arcuate, inferior fronto-occipital, and middle longitudinal fascicles, and optic
      radiations. Surgical resection was planned in 2 separate stages. The first stage
      consisted of a transsylvian transinferior insular sulcus approach to the extra-
      and intraventricular aspects of the uncohippocampal region. The entire anterior
      and middle portions of the tumor were successfully removed with minimal
      morbidity, including transient naming difficulties and permanent superior
      quadrantanopia. Postoperative HDFT showed preservation of all fiber tracts,
      except for a portion of Meyer's loop and the inferior-most aspect of the inferior
      fronto-occipital fascicle. The second stage was completed 8 wk later and
      consisted of a paramedian supracerebellar-transtentorial approach on sitting
      position. The posterior portion of the tumor was entirely removed to achieve a
      complete macroscopic tumor resection. The final diagnosis was IDH1-positive LGG.
      Pan-hippocampal tumors remain a surgical challenge but accurate knowledge of
      surgical neuroanatomy and surgical approaches facilitates their safe and
      effective treatment. The patient signed an informed consent including the use of
      photographic and video material for educational or academic purposes.

PMID- 30295905
TI  - Gnp4/LAX2, a RAWUL protein, interferes with the OsIAA3-OsARF25 interaction to
      regulate grain length via the auxin signaling pathway in rice.
AB  - Grain length is one of the determinants of yield in rice and auxin plays an
      important role in regulating it by mediating cell growth. Although several genes
      in the auxin pathway are involved in regulating grain length, the underlying
      molecular mechanisms remain unclear. In this study we identify a RING-finger and
      wd40-associated ubiquitin-like (RAWUL) domain-containing protein, Gnp4/LAX2, with
      a hitherto unknown role in regulation of grain length by its influence on cell
      expansion. Gnp4/LAX2 is broadly expressed in the plant and subcellular
      localization analysis shows that it encodes a nuclear protein. Overexpression of
      Gnp4/LAX2 can significantly increase grain length and thousand-kernel weight.
      Moreover, Gnp4/LAX2 physically interacts with OsIAA3 and consequently interferes
      with the OsIAA3-OsARF25 interaction in vitro and in vivo. OsIAA3 RNAi plants
      consistently exhibit longer grains, while the mutant osarf25 has small grains. In
      addition, OsARF25 binds to the promoter of OsERF142/SMOS1, a regulator of organ
      size, and positively regulates its expression. Taken together, the results reveal
      that Gnp4/LAX2 functions as a regulator of grain length through participation in
      the OsIAA3-OsARF25-OsERF142 pathway and that it has potential value for molecular
      breeding in rice.

PMID- 30295908
TI  - Generalized Bootstrap Supports for Phylogenetic Analyses of Protein Sequences
      Incorporating Alignment Uncertainty.
AB  - Phylogenetic reconstructions are essential in genomics data analyses and depend
      on accurate multiple sequence alignment (MSA) models. We show that all currently
      available large-scale progressive multiple alignment methods are numerically
      unstable when dealing with amino-acid sequences. They produce significantly
      different output when changing sequence input order. We used the HOMFAM protein
      sequences dataset to show that on datasets larger than 100 sequences, this
      instability affects on average 21.5% of the aligned residues. The resulting
      Maximum Likelihood (ML) trees estimated from these MSAs are equally unstable with
      over 38% of the branches being sensitive to the sequence input order. We
      established that about two-thirds of this uncertainty stems from the unordered
      nature of children nodes within the guide trees used to estimate MSAs. To
      quantify this uncertainty we developed unistrap, a novel approach that estimates
      the combined effect of alignment uncertainty and site sampling on phylogenetic
      tree branch supports. Compared with the regular bootstrap procedure, unistrap
      provides branch support estimates that take into account a larger fraction of the
      parameters impacting tree instability when processing datasets containing a large
      number of sequences.

PMID- 30295909
TI  - Mesenteric Adipose Tissue Alterations in Crohn's Disease Are Associated With the
      Lymphatic System.
AB  - Background: Mesenteric fat wrapping and thickening are typical characteristics of
      Crohn's disease (CD). The purpose of this study was to explore the cause of
      mesenteric adipose hypertrophy and analyze the role of lymphatic vessels in
      mesenteric adipose tissue in CD. Methods: Twenty-three CD patients who underwent
      ileocolonic resection were included. In CD patients, specimens were obtained from
      hypertrophic mesenteric adipose tissue (htMAT) next to the diseased ileum. The
      mesenteric lymphatic vessels in mesenteric adipose tissue were separated under
      stereoscope microscope. Transmission electron microscopy and immunofluorescence
      were used to observe the structure of mesenteric lymphatic vessels. The NF-kappaB
      signaling pathway in mesenteric adipose tissue was detected in CD specimens using
      Western blotting. Results: Electron microscopy showed that the structure of
      mesenteric lymphatic vessel was discontinuous, and the microstructure of
      lymphatic endothelial cells appeared ruptured and incomplete. Through an
      immunofluorescence technique, we found that the surface of lymphatic endothelial
      cells lacked tight junction protein staining in CD. Also, the expression of
      claudin-1, occludin, and ZO-1 in the mesenteric lymphatic vessel of htMAT was
      significantly lower than that of control. These results indicated that the
      structure of the mesenteric lymphatic vessel in htMAT was mispatterned and
      ruptured, which could lead to lymph leakage. Leaky lymph factors could stimulate
      adipose tissue to proliferate. Antigens that leaked into the mesenteric adipose
      tissue could effectively elicit an immune response. The levels of cytokines (TNF
      a, IL-1beta, IL-6) was increased in the htMAT of CD patients by activated NF
      kappaB signaling pathway. Conclusions: Our findings demonstrated that the
      hypertrophy of mesenteric adipose tissue may result from mispatterned and
      ruptured lymphatic vessels. Alteration of mesenteric adipose tissue was
      associated with activated NF-kappaB signaling pathway. This study enhances
      support for elucidating the importance of mesenteric lymphatic vessels and
      adipose tissue in CD.

PMID- 30295910
TI  - Resorcylic Acid Lactones in Urine Samples of Croatian Farm Animals.
AB  - Metabolic transformation of zearalenone (ZEA), a mycotoxin which can contaminate
      both food and feed, results in the formation of five metabolites, one of them
      being zeranol (alpha-ZAL), which can be abused in farm animals as a growth
      promoter. To the best of our knowledge, there is no analytical method that can
      distinguish whether alpha-ZAL is present in an animal urine sample as a result of
      ZEA biotransformation or as a result of anabolic abuse. This study aimed at
      monitoring resorcylic acid lactones (RALs) concentration in urine of farm animals
      over several years. Six hundred and three cattle and pig urine samples were
      collected on farms in different Croatian regions and analyzed for RAL presence.
      Based on the testing results, all RAL-positive samples were considered to be
      consequential to feed contamination. The difference in primary ZEA metabolites'
      ratio (alpha-zearalenol/beta-zearalenol) was observed between cattle (0.03-0.41)
      and pig (2.05-17.39) urine samples. If the animals are treated with alpha-ZAL and
      fed on ZEA-contaminated feed, alpha-ZAL and taleranol found in their organisms
      could come from two sources, so that the reliability of the statistical model
      might be questionable. Based on these findings, there exists the need for
      improving the approach to the distinction between alpha-ZAL abuse and ZEA feed
      contamination.

PMID- 30295911
TI  - Verticillium dahliae Alt a 1-like protein PevD1 targets cotton PR5-like protein
      and contributes to fungal infection.
AB  - Alt a 1 family proteins (AA1s) have only been observed in the Dothideomycetes and
      Sordariomycetes classes of fungi, and their biological functions have been poorly
      understood to date. Verticillium dahliae, a soil-borne pathogen that causes plant
      verticillium wilt disease, secretes hundreds of proteins during the process of
      pathogenic infection, including the AA1s member PevD1. The pevd1 transcript was
      present in all of the hosts studied and showed elevated expression throughout the
      infection process. Furthermore, pevd1 knockout mutants displayed attenuated
      pathogenicity compared with the wild type (WT) strain and complemented strains in
      hosts. A partner protein of PevD1, pathogenesis-related protein 5 (PR5)-like
      protein GhPR5, was isolated from cotton plants by co-purification assays, and the
      PevD1-GhPR5 interaction was further confirmed by a pull-down assay. The GhPR5
      interacting region of PevD1 was determined to be located in the C-terminus
      (PevD1b, amino acids residues 113-155) via pull-down and Y2H techniques.
      Reintroduction of the pevd1b gene into a pevd1 knockout mutant resulted in
      restoration of the virulence phenotype to WT levels. Moreover, PevD1b, similar to
      PevD1, decreased the antifungal activity of GhPR5 in vitro. Our findings
      highlight a new infection strategy in which V. dahliae secretes PevD1 to inhibit
      GhPR5 antifungal activity to overcome the host defence system.

PMID- 30295912
TI  - Yoga as a Complementary Therapy for Smoking Cessation: Results from BreathEasy ,a
      Randomized Clinical trial.
AB  - Introduction: There is evidence that yoga may be helpful as an aid for smoking
      cessation. Yoga has been shown to reduce stress and negative mood and may aid
      weight control, all of which have proven to be barriers to quitting smoking. This
      study is the first rigorous, randomized clinical trial of yoga as a complementary
      therapy for smokers attempting to quit. Methods: Adult smokers (n=227; 55% women)
      were randomized to an 8-week program of cognitive-behavioral smoking cessation
      and either twice-weekly Iyengar Yoga, or general Wellness classes (control).
      Assessments included cotinine verified 7-day point prevalence abstinence (7PPA)
      at week 8, 3-month and 6-month follow-ups. Results: At baseline participants'
      mean age was 46.2 years (SD=12.0), smoking rate 17.3 cigarettes/day (SD=7.6).
      Longitudinally adjusted models of abstinence outcomes demonstrated significant
      group effects favoring Yoga. Yoga participants had 37% greater odds of achieving
      abstinence than Wellness participants at EOT. Lower baseline smoking rates (<=10
      cigarettes/day) were also associated with higher likelihood of quitting if given
      Yoga vs. Wellness (OR=2.43, 95% CI: 1.09-6.30) at EOT. A significant dose effect
      was observed for yoga (OR=1.12, 95% CI: 1.09-1.26), but not Wellness, such that
      each yoga class attended increased quitting odds at EOT by 12%. Latent Class
      Modeling revealed a 4-class model of distinct quitting patterns among
      participants. Conclusions: Yoga appears to increase the odds of successful
      smoking abstinence, particularly among light smokers. Additional work is needed
      to identify predictors of quitting patterns and inform adjustments to therapy
      needed to achieve cessation and prevent relapse.

PMID- 30295913
TI  - The impact of coronary angiography on renal transplant function.
AB  - Background: There may be reluctance to perform coronary angiography in kidney
      transplant patients due to perceived risk of iodinated contrast, despite an
      increased risk of cardiovascular disease compared with the general population.
      Aim: We sought to determine if renal transplant function was adversely affected
      within 7, 30 and 180 days of coronary angiography. Methods: Renal transplant
      recipients undergoing coronary angiography in a single centre (01/2006-02/2018)
      were identified retrospectively. Baseline and highest SCr within 7, 30 and 180
      days of coronary angiography were extracted from the electronic patient record.
      Rise in creatinine >26 micromol/l was considered significant (equivalent to Acute
      Kidney Injury (AKI) Network criteria stage 1 AKI) and case note review performed
      to determine circumstance of renal decline. Results: There were 127 coronary
      angiographies conducted in 90 patients: 67.7% were male and mean age was 58.0 (+/
      10.1) years. There was AKI within 7 days in 18.9% cases, but SCr returned to
      baseline within 7 days or there was an alternative explanation for AKI in 83.3%
      of these. In the remaining 4 cases, there was progressive decline in renal
      transplant function. In the absence of critical illness, no patient required
      dialysis or extended hospital stay for contrast-associated AKI. Conclusions: In
      this cohort of renal transplant recipients undergoing coronary angiography, AKI
      occurred in a minority of cases, and in more than 95% of such cases this effect
      was transient, with progressive renal decline a rare and predictable event. Renal
      transplant should not be regarded as a contraindication to coronary angiography.

PMID- 30295914
TI  - Mindfulness and progressive muscle relaxation as standardized session
      introduction in individual therapy: A randomized controlled trial.
AB  - OBJECTIVE: There is scarce research on the effects of mindfulness in individual
      therapy. As many practitioners integrate mindfulness exercises into individual
      therapy, empirical evidence is of high clinical relevance. METHOD: We
      investigated the effects of a session-introducing intervention with mindfulness
      elements (SIIME) in a randomized, controlled design. The effects of SIIME on
      therapeutic alliance and symptomatic outcome were compared with progressive
      muscle relaxation (PMR) and treatment-as-usual (TAU) control conditions. The
      sample comprised 162 patients with anxiety and depression. RESULTS: Multilevel
      modeling revealed a significant symptom reduction and significant increase of
      alliance over the course of therapy. There were no significant time-condition
      interactions on outcome and alliance, indicating the comparable efficiency of all
      three treatment conditions. CONCLUSIONS: We found no advantage of SIIME versus
      PMR and TAU. Add-on mindfulness might not improve individual therapy related to
      alliance and outcome.

PMID- 30295915
TI  - Discrimination and Ethnic-Racial Socialization Among Youth Adopted From South
      Korea Into White American Families.
AB  - The current study examined how discrimination relates to adjustment outcomes in a
      sample of internationally, transracially adopted Korean Americans from the
      Minnesota Sibling Interaction and Behavior Study (N = 456 adoptees; Mage at T1 =
      14.9, Mage at T2 = 18.3, Mage at T3 = 22.3). The moderating roles of ethnic
      socialization and preparation for bias by parents (i.e., ethnic-racial
      socialization) were also examined. Results indicated that discrimination
      predicted higher levels of depressive and externalizing symptoms in youth who
      reported less preparation for bias. In those experiencing more preparation for
      bias, associations were not significantly different from zero. Ethnic
      socialization did not moderate these associations. Such findings provide
      important information for adoptive parents regarding how to prepare their
      children to cope with discrimination.

PMID- 30295916
TI  - Astrocyte support is important for the compensatory potential of the
      nigrostriatal system neurons during early neurodegeneration.
AB  - Glial pathology precedes symptoms of Parkinson's disease (PD) and multiple other
      neurodegenerative diseases. Prolonged impairment of astrocytic functions could
      increase the vulnerability of dopaminergic neurons in the substantia nigra (SN),
      accelerate their degeneration and affect ability to compensate for partial
      degeneration at the presymptomatic stages of the disease. The aim of this study
      was to investigate the astrocyte depletion in the SN, its impact on the
      dopaminergic system functioning and multiple markers of energy metabolism during
      the early stages of neurodegeneration and compensation. We induced death of 30%
      of astrocytes by chronic infusion of fluorocitrate (FC) into the SN,
      simultaneously activating microglia response but sparing the dopaminergic
      neurons. The FC effect was reversible after toxin withdrawal. Dopaminergic
      neurons were killed by 6-hydroxydopamine causing transient locomotor disability,
      reversed with time showing compensatory potential. Death of astrocytes diminished
      the capability of the dopaminergic system to compensate for the degeneration of
      neurons and caused a local energy deprivation by decreasing lactate and glycogen
      amount. Studied markers suggest a shift in the usage of energy substrates, via
      increased glycogenolysis and glycolysis markers, ketone bodies availability and
      fatty acid transport in remaining glial cells. PGC-1alpha and AMPK, the energy
      sensors, showed different regulation between the cell-types. Increased neuronal
      expression of CPT1c could play a role in the adaptation to metabolic stress in
      response to glia dysfunction. Astrocyte energetic support is one of the essential
      factors for neuronal compensatory mechanisms of dopaminergic system and might
      have a leading role in the presymptomatic PD stages. This article is protected by
      copyright. All rights reserved.

PMID- 30295917
TI  - Preparation and Characterization of Lactobacilli-Loaded Composite Films with
      Sustaining Antipathogenic Activity and Preservation Effect.
AB  - : Bioactive composite films were obtained by adding Lactobacillus paracasei into
      a hydroxypropyl cellulose (HPC)-konjac flour (KF) matrix through a casting
      method. The mechanical, optical, and barrier properties were tested to determine
      the influence of the addition of lactobacilli into complex films. For purpose of
      evaluating the surface morphology of the composite films, scanning electron
      microscopy and atomic force microscopy were carried out. Fourier transform
      infrared spectroscopy and X-ray diffraction analyses were conducted to evaluate
      intermolecular interactions and crystallinity, respectively. Moreover, the
      microbial viability of the lactobacilli and the antibacterial activities of the
      bioactive films against pathogenic organisms were measured. The results indicated
      that the mechanical properties, crystalline properties, oxygen permeability, and
      color characteristics were not notably altered; nevertheless, the gloss and water
      vapor barrier properties were relatively weakened by the incorporation of L.
      paracase. The HPC-KF-L. paracasei films were effective in inhibiting both gram
      positive (Listeria monocytogenes, Staphylococcus aureus) and gram-negative
      (Escherichia coli, Salmonella typhimurium) pathogens, and the films can retain
      physical property and antibacterial activity within a storage period of 30 days.
      The composite films, acting as suitable carriers for L. paracasei and possessing
      noteworthy bacteriostatic activities, could be developed as bioactive packaging
      for preserving food. PRACTICAL APPLICATION: For the sake of the high desires of
      consumers for food safety and quality, the development of innovative bioactive
      packaging has attracted wide attention. In this work, the prepared films
      containing lactic acid bacteria showed great physical property, antipathogenic
      activity, and fresh-keeping property preservation, and have great application
      potential in fresh food preservation.

PMID- 30295918
TI  - The Impact of Caregiving Disruptions of Previously Institutionalized Children on
      Multiple Outcomes in Late Childhood.
AB  - This study examined disruptions in caregiving, as well as the association of
      these disruptions, with cognitive, behavioral, and social outcomes at age 12 in a
      sample of 136 Romanian children who were abandoned to institutions as infants and
      who experienced a range of subsequent types of care. Children were found to
      experience significantly more caregiving disruptions (CGD) earlier in life than
      later in childhood. More frequent CGD predicted increases in externalizing and
      internalizing behavior problems at age 12. Results are discussed in terms of the
      association between CGD and the long-term development of children who have
      experienced institutional rearing.

PMID- 30295919
TI  - Methamphetamine decreases K+ channel function in human fetal astrocytes by
      activating the trace amine-associated receptor type-1.
AB  - Methamphetamine (Meth) is a potent and commonly abused psychostimulant. Meth
      alters neuron and astrocyte activity; yet the underlying mechanism(s) is not
      fully understood. Here we assessed the impact of acute Meth on human fetal
      astrocytes (HFAs) using whole-cell patch-clamping. We found that HFAs displayed a
      large voltage-gated K+ efflux (IKv ) through Kv /Kv -like channels during
      membrane depolarization, and a smaller K+ influx (Ikir ) via inward-rectifying
      Kir /Kir -like channels during membrane hyperpolarization. Meth at a
      'recreational' (20 MUM) or toxic/fatal (100 MUM) concentration depolarized
      resting membrane potential (RMP) and suppressed IKv/Kv-like . These changes were
      associated with a decreased time constant (T), and mimicked by blocking the two
      pore domain K+ (K2P )/K2P -like and Kv /Kv -like channels, respectively. Meth
      also diminished IKir/Kir-like , but only at toxic/fatal levels. Given that Meth
      is a potent agonist for the trace amine-associated receptor type-1 (TAAR1), and
      TAAR1-coupled cAMP/cAMP-activated protein kinase (PKA) cascade, we further
      evaluated whether the Meth impact on K+ efflux was mediated by this pathway. We
      found that antagonizing TAAR1 with N-(3-Ethoxyphenyl)-4-(1-pyrrolidinyl)-3
      (trifluoromethyl)benzamide (EPPTB) reversed Meth-induced suppression of IKv/Kv
      like ; and inhibiting PKA activity by H89 abolished Meth effects on suppressing
      IKv/Kv-like . Antagonizing TAAR1 might also attenuate Meth-induced RMP
      depolarization. Voltage-gated Ca2+ currents were not detected in HFAs. These
      novel findings demonstrate that Meth suppresses IKv/Kv-like by facilitating the
      TAAR1/Gs /cAMP/PKA cascade and altering the kinetics of Kv /Kv -like channel
      gating, but reduces K2P /K2P -like channel activity through other pathway(s), in
      HFAs. Given that Meth-induced decrease in astrocytic K+ efflux through K2P /K2P 
      like and Kv /Kv -like channels reduces extracellular K+ levels, such reduction
      could consequently contribute to a decreased excitability of surrounding neurons.
      Open Data: Materials are available on https://cos.io/our-services/open-science
      badges/ https://osf.io/93n6m/.

PMID- 30295920
TI  - Development, behaviour and autism in individuals with SMC1A variants.
AB  - INTRODUCTION: Development and behaviour in Cornelia de Lange Syndrome (CdLS),
      including autism characteristics, have been described infrequently stratified to
      genetic cause and only a few studies have considered behavioural characteristics
      in relation to developmental level. Here, we describe the behavioural phenotype
      in individuals with CdLS with SMC1A variants. METHODS: We performed an
      international, interdisciplinary study on 51 individuals with SMC1A variants.
      Results of questionnaire studies are compared to those in individuals with Down
      Syndrome and with Autism Spectrum Disorder. Results on cognition and self
      injurious behaviour (SIB) are compared to those in individuals with CdLS caused
      by NIPBL variants. For Dutch participants with SMC1A variants we performed direct
      in-person assessments of cognition, autism, and added an interview and
      questionnaire on adaptive behaviour and sensory processing. RESULTS: Individuals
      with SMC1A variants show a higher cognitive level and less SIB than individuals
      with NIPBL variants. Individuals with SMC1A variants without classic CdLS
      phenotype but with a Rett-like phenotype show more severe intellectual disability
      and more SIB compared to those with a CdLS phenotype. Autism is less present if
      outcomes in direct in-person assessments are evaluated taking developmental level
      into account compared to results based on a questionnaire. CONCLUSIONS: Behaviour
      in individuals with CdLS should be evaluated taking genetic cause into account.
      Detailed interdisciplinary approaches are of clinical importance to inform
      tailored care and may eventually improve quality of life of patients and
      families.

PMID- 30295921
TI  - Keys to the Gate? Equal Sign Knowledge at Second Grade Predicts Fourth-Grade
      Algebra Competence.
AB  - Algebraic competence is a major determinant of college access and career
      prospects, and equal sign knowledge is taken to be foundational to algebra
      knowledge. However, few studies have documented a causal effect of early equal
      sign knowledge on later algebra skill. This study assessed whether second-grade
      students' equal sign knowledge prospectively predicts their fourth-grade algebra
      knowledge, when controlling for demographic and individual difference factors.
      Children (N = 177; Mage = 7.61) were assessed on a battery of tests in Grade 2
      and on algebraic knowledge in Grade 4. Second-grade equal sign knowledge was a
      powerful predictor of these algebraic skills. Findings are discussed in terms of
      the importance of foregrounding equal sign knowledge to promote effective
      pedagogy and educational equity.

PMID- 30295922
TI  - Oral health and access to dental care among older homeless adults: results from
      the HOPE HOME study.
AB  - OBJECTIVES: To describe the prevalence of and factors associated with oral health
      measures in a sample of older homeless adults in Oakland, CA. METHODS: We
      conducted a cross-sectional analysis of data from a population-based study of 350
      homeless adults aged >=50 in which trained researchers conducted structured
      interviews using validated questions regarding sociodemographics, health-related
      behaviors, healthcare utilization, and health status. We assessed self-reported
      tooth loss, oral pain, and unmet need for dental care. We used multivariable
      logistic regression to examine factors associated with missing half or more
      teeth. RESULTS: Over half 201/350 (57.4 percent) of participants were missing at
      least half of their teeth. Half 191/350 (54.6 percent) reported oral pain in the
      past 6 months; 101/350 (28.9 percent) reported that oral pain prevented them from
      eating and 73/350 (20.9 percent) reported that pain prevented sleeping. Almost
      half, 141/350 (40.3 percent), had not seen a dentist in over 5 years, and over
      half 190/350 (54.3 percent) reported being unable to obtain needed dental care.
      In multivariate models, increased age (AOR = 1.09, 95 percent CI 1.04-1.14),
      moderate-to-high risk alcohol use (AOR = 2.17, CI = 1.23-3.84), moderate-to-high
      risk cocaine use (AOR = 1.72, CI = 1.03-2.88), and ever smoking (AOR = 2.87, CI =
      1.59-5.18) were associated with an increased odds of having lost half or more
      teeth. CONCLUSIONS: Tooth loss and oral pain are highly prevalent in older
      homeless adults. Increasing age, alcohol, drug, and tobacco use are associated
      with tooth loss.

PMID- 30295923
TI  - Slow periodic activity in the longitudinal hippocampal slice can self-propagate
      non-synaptically by a mechanism consistent with ephaptic coupling.
AB  - KEY POINTS: Slow periodic activity can propagate with speeds around 0.1 m s-1 and
      be modulated by weak electric fields. Slow periodic activity in the longitudinal
      hippocampal slice can propagate without chemical synaptic transmission or gap
      junctions, but can generate electric fields which in turn activate neighbouring
      cells. Applying local extracellular electric fields with amplitude in the range
      of endogenous fields is sufficient to modulate or block the propagation of this
      activity both in the in silico and in the in vitro models. Results support the
      hypothesis that endogenous electric fields, previously thought to be too small to
      trigger neural activity, play a significant role in the self-propagation of slow
      periodic activity in the hippocampus. Experiments indicate that a neural network
      can give rise to sustained self-propagating waves by ephaptic coupling,
      suggesting a novel propagation mechanism for neural activity under normal
      physiological conditions. ABSTRACT: Slow oscillations are a standard feature
      observed in the cortex and the hippocampus during slow wave sleep. Slow
      oscillations are characterized by low-frequency periodic activity (<1 Hz) and are
      thought to be related to memory consolidation. These waves are assumed to be a
      reflection of the underlying neural activity, but it is not known if they can, by
      themselves, be self-sustained and propagate. Previous studies have shown that
      slow periodic activity can be reproduced in the in vitro preparation to mimic in
      vivo slow oscillations. Slow periodic activity can propagate with speeds around
      0.1 m s-1 and be modulated by weak electric fields. In the present study, we show
      that slow periodic activity in the longitudinal hippocampal slice is a self
      regenerating wave which can propagate with and without chemical or electrical
      synaptic transmission at the same speeds. We also show that applying local
      extracellular electric fields can modulate or even block the propagation of this
      wave in both in silico and in vitro models. Our results support the notion that
      ephaptic coupling plays a significant role in the propagation of the slow
      hippocampal periodic activity. Moreover, these results indicate that a neural
      network can give rise to sustained self-propagating waves by ephaptic coupling,
      suggesting a novel propagation mechanism for neural activity under normal
      physiological conditions.

PMID- 30295924
TI  - Correction to: Polymorphisms of genes involved in inflammation and blood vessel
      development influence the risk of varicose veins.

PMID- 30295925
TI  - Identification of drug transporters contributing to oxaliplatin-induced
      peripheral neuropathy.
AB  - Oxaliplatin is widely used as a key drug in the treatment of colorectal cancer.
      However, its administration is associated with the dose-limiting adverse effect,
      peripheral neuropathy. Platinum accumulation in the dorsal root ganglion (DRG) is
      the major mechanism responsible for oxaliplatin-induced neuropathy. Some drug
      transporters have been identified as platinum complex transporters in kidney or
      tumor cells, but not yet in DRG. In the present study, we investigated
      oxaliplatin transporters and their contribution to peripheral neuropathy. We
      identified 12 platinum transporters expressed in DRG with real-time PCR, and
      their transiently overexpressing cells were established. After exposure to
      oxaliplatin, the accumulation of platinum in these overexpressing cells was
      evaluated using a coupled plasma mass spectrometer. Octn1/2- and Mate1-expressing
      cells showed the intracellular accumulation of oxaliplatin. In an animal study,
      peripheral neuropathy developed after the administration of oxaliplatin (4 mg/kg,
      intravenously, twice a week) to siRNA-injected rats (0.5 nmol, intrathecally,
      once a week) was demonstrated with the von Frey test. The knockdown of Octn1 in
      DRG ameliorated peripheral neuropathy, and decreased platinum accumulation in
      DRG, whereas the knockdown of Octn2 did not. Mate1 siRNA-injected rats developed
      more severe neuropathy than control rats. These results indicate that Octn1 and
      Mate1 are involved in platinum accumulation at DRG and oxaliplatin-induced
      peripheral neuropathy.

PMID- 30295926
TI  - From Amazonia to southern Africa: atmospheric moisture transport through low
      level jets and atmospheric rivers.
AB  - A Lagrangian analysis is applied to identify the main moisture source areas
      associated with atmospheric rivers (ARs) making landfall along the west coast of
      South Africa during the extended austral winter months from 1980 to 2014. The
      results show that areas that provide the anomalous uptake of moisture can be
      categorized into four regions: (1) the South Atlantic Ocean between 10 degrees S
      and 30 degrees S, (2) a clear local maximum in the eastern South Atlantic, (3) a
      continental source of anomalous uptake to the north of the Western Cape, and (4)
      over South America at a distance of more than 7000 km from the target region. It
      emerges that the South American moisture source can be linked to a particular
      phase of the South American low-level jet, known as a no Chaco jet event (NCJE),
      which transports moisture to the western and central South Atlantic basin.
      Concisely, we provide strong evidence that the two margins of the South Atlantic
      Ocean appear connected by two meteorological structures, with the NCJE playing a
      key role of transporting moisture from South America to the western and central
      South Atlantic basin, feeding the AR that transports some of the moisture to the
      west coast of South Africa.

PMID- 30295927
TI  - Long-Term Acute Care Hospital Use of Non-Mechanically Ventilated Hospitalized
      Older Adults.
AB  - OBJECTIVES: To determine why non-mechanically ventilated hospitalized older
      adults are transferred to long-term acute care (LTAC) hospitals rather than
      remaining in the hospital. DESIGN: Observational cohort. SETTING: National
      Medicare data. PARTICIPANTS: Non-mechanically ventilated hospitalized adults aged
      65 and older with fee-for-service Medicare in 2012 who were transferred to an
      LTAC hospital (n=1,831) or had a prolonged hospitalization without transfer
      (average hospital length of stay or longer of those transferred to an LTAC
      hospital) and had one of the 50 most common hospital diagnoses leading to LTAC
      transfer (N=12,875). MEASUREMENTS: We assessed predictors of transfer using a
      multilevel model, adjusting for patient-, hospital-, and hospital referral region
      (HRR)-level factors. We estimated proportions of variance at each level and
      adjusted hospital- and HRR-specific LTAC transfer rates using sequential models.
      RESULTS: The strongest predictor of transfer was being hospitalized near an LTAC
      hospital (<1.4 vs > 33.6 miles, adjusted odds ratio=6.2, 95% confidence interval
      (CI)=4.2-9.1). After adjusting for case mix, differences between hospitals
      explained 15.4% of the variation in LTAC use and differences between regions
      explained 27.8%. Case mix-adjusted LTAC use was high in the South, where many
      HRRs had rates between 20.3% and 53.1%, whereas many HRRs were less than 5.4% in
      the Pacific Northwest, North, and New England. From our fully adjusted model, the
      median adjusted hospital LTAC transfer rate was 7.2% (interquartile range 2.8
      17.5%), with substantial within-region variation (intraclass coefficient=0.25,
      95% CI=0.21-0.30). CONCLUSIONS: Nearly half of the variation in LTAC use is
      independent of illness severity and is explained by which hospital and what
      region the individual was hospitalized in. Because of the greater fragmentation
      of care and Medicare spending with LTAC transfers (because LTAC hospitals
      generate a separate bundled payment from the hospital), greater attention is
      needed to define the optimal role of LTAC hospitals in caring for older adults. J
      Am Geriatr Soc 66:2112-2119, 2018.

PMID- 30295928
TI  - Terrestrial LiDAR: a three-dimensional revolution in how we look at trees.
AB  - Contents Summary I. Introduction II. Terrestrial laser scanning III. Turning
      points into trees IV. Current and future applications of TLS V. Conclusions
      Acknowledgements References SUMMARY: Terrestrial laser scanning (TLS) is
      providing new, very detailed three-dimensional (3D) measurements of forest canopy
      structure. The information that TLS measurements can provide in describing
      detailed, accurate 3D canopy architecture offers fascinating new insights into
      the variety of tree form, environmental drivers and constraints, and the
      relationship between form and function, particularly for tall, hard-to-measure
      trees. TLS measurements are helping to test fundamental ecological theories and
      enabling new and better exploitation of other measurements and models that depend
      on 3D structural information. This Tansley insight introduces the background and
      capabilities of TLS in forest ecology, discusses some of the barriers to
      progress, and identifies some of the directions for new work.

PMID- 30295929
TI  - Prediction models for postoperative uncontrolled chronic rhinosinusitis in daily
      practice.
AB  - OBJECTIVES/HYPOTHESIS: The European Position Paper on Rhinosinusitis and Nasal
      Polyps proposes an assessment of clinical control of chronic rhinosinusitis
      (CRS). However, there are limited data about the percentage of postoperative
      control, and no prediction models for uncontrolled CRS have been reported. The
      aim of the study was to develop prediction models for postoperative uncontrolled
      CRS. STUDY DESIGN: Retrospective case series. METHODS: Patients (n = 136) who had
      undergone endoscopic sinus surgery at least 1 year prior to the study were
      recruited to assess the clinical control. Risk factors were determined by
      logistic models and presented as odds ratio (OR) with a 95% confidence interval.
      Receiver operating characteristics curves were constructed to set the cutoff
      points and create predictive models. RESULTS: Approximately 47.8% of patients had
      controlled, 22.1% partially controlled, and 30.1% uncontrolled CRS. Univariate
      regression models revealed the risk factors for uncontrolled CRS: tissue
      eosinophilia, blood eosinophilia, high computed tomography (CT) score, bilateral
      disease, asthma, and allergic rhinitis. Multiple regression models found tissue
      eosinophil ratio >0.206 (OR: 12.96, P = .001) or blood eosinophil ratio >0.025
      (OR: 4.56, P = .003), Lund-Mackay (LM) score >= 15 (OR: 15.50, P < .001) and CT
      ethmoid (E) score >= maxillary (M) score (OR: 3.51, P = .037) were independent
      risk factors. We generated a pathological model (tissue eosinophil ratio and LM
      score) and a clinical model (blood eosinophil ratio, LM score and E >= M score)
      to categorize CRS into mild, moderate, and severe. CONCLUSIONS: This research
      provides simplified and efficient prediction models for uncontrolled CRS. It may
      help otolaryngologists to predict the prognosis before surgery in daily practice.
      LEVEL OF EVIDENCE: 2b Laryngoscope, 2018.

PMID- 30295930
TI  - Gastroenteropancreatic Neuroendocrine Tumors.
AB  - Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from the
      diffuse neuroendocrine system. They frequently originate in the
      gastroenteropancreatic (GEP) tract and the bronchopulmonary tree, and their
      incidence has steadily increased in the last 3 decades. Fundamental biologic and
      genomic differences underlie the clinical heterogeneity of NETs, and distinct
      molecular features characterize NETs of different grades and different primary
      sites. Although surgery remains the cornerstone of treatment for localized
      tumors, systemic treatment options for patients with metastatic NETs have
      expanded considerably. Somatostatin analogs have demonstrated both antisecretory
      and antitumor efficacy. Peptide receptor radionuclide therapy with lutetium-177
      dotatate (177 Lu-DOTATATE) has been approved for advanced GEP-NETs. The antitumor
      activity of everolimus has been demonstrated across a wide spectrum of NETs, and
      the antiangiogenic agent sunitinib has been approved for pancreatic NETs (pNETs).
      Chemotherapy with temozolomide and capecitabine has recently demonstrated an
      unprecedented prolongation of progression-free survival in a randomized trial of
      pNETs. Multiple retrospective series have reported the efficacy of liver-directed
      therapies both for palliating symptoms of hormone excess and for controlling
      tumor growth. Telotristat, an oral inhibitor of tryptophan hydroxylase, has been
      shown to reduce diarrhea in patients with carcinoid syndrome. Defining the
      therapeutic algorithm and identifying biomarkers predictive of response to
      treatments are among the main priorities for the next decade of research in the
      NET field.

PMID- 30295931
TI  - Feasibility study of combined dynamic imaging and lymphaticovenous anastomosis
      surgery for breast cancer-related lymphoedema.
AB  - BACKGROUND: Breast cancer-related lymphoedema (BCRL) presents a significant
      healthcare burden and adversely affects quality of life of breast cancer
      survivors. A prospective feasibility study was performed on lymphaticovenous
      anastomosis (LVA) for the treatment of BCRL. METHODS: Patients with BCRL
      underwent near-infrared spectroscopy with indocyanine green lymphatic mapping to
      identify suitable lymphatic channels for LVA. End-to-end anastomoses to subdermal
      venules were performed and patients recommenced compression garment therapy (CGT)
      after surgery. Volumetric assessment of the affected limb was performed at
      regular intervals using infrared perometry to calculate the excess volume
      reduction. RESULTS: Over a 24-month interval, 27 patients with BCRL underwent
      LVA. The mean duration of lymphoedema was 3.5 (range 0.5-18) years, and the mean
      number of LVAs performed was 3 (range 2-5). Twenty-four of the 27 patients
      completed 12-month follow-up. Patients exhibited three patterns of volumetric
      response following LVA: sustained response (16 patients), transient response (5)
      or no response (6). Sustained responders showed an excess volume reduction of 
      33.2 per cent at 12 months, and this correlated positively with the number of
      LVAs performed (r = -0.56, P = 0.034). Overall, ten patients were able to
      downgrade CGT after surgery, and two patients were CGT-free at 12 months.
      CONCLUSION: LVA resulted in a sustained volume reduction in selected patients and
      may offset the burden of CGT. Further work is required to identify biomarkers
      that predict a favourable response to LVA surgery.

PMID- 30295932
TI  - Effect of marital relationship on women's quality of life: Testing the mediating
      role of subjective well-being.
AB  - Because of a large number of Chinese women and the widespread concern about
      women's living conditions, this study aimed to examine how subjective well-being
      mediates the association between marital relationship and women's quality of life
      in Chinese context. The data used in this study were collected by conducting a
      multi-stage cluster random sampling method of 756 women in Huai'an city of
      Mainland China. Data included women's basic demographics, women's quality of life
      and marital quality, and women's subjective well-being. Structural equation
      modeling was adopted to analyze the data. The results of structural equation
      modeling analysis suggested a good fit for the sample. Overall findings showed
      that marital relationship has a significantly direct effect on women's quality of
      life, and subjective well-being can partially mediate the impact of marital
      relationship on women's quality of life. The implications on theory and social
      policy were also discussed.

PMID- 30295933
TI  - Hereditary transthyretin-related amyloidosis.
AB  - Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an
      endemic/non-endemic, autosomal-dominant, early- and late-onset, rare, progressive
      disorder, predominantly manifesting as length-dependent, small fiber dominant,
      axonal polyneuropathy and frequently associated with cardiac disorders and other
      multisystem diseases. ATTRm amyloidosis is due to variants in the TTR gene, with
      the substitution Val30Met as the most frequent mutation. TTR mutations lead to
      destabilization and dissociation of TTR tetramers into variant TTR monomers, and
      formation of amyloid fibrils, which are consecutively deposited extracellularly
      in various tissues, such as nerves, heart, brain, eyes, intestines, kidneys, or
      the skin. Neuropathy may not only include large nerve fibers but also small
      fibers, and not only sensory and motor fibers but also autonomic fibers. Types of
      TTR variants, age at onset, penetrance, and clinical presentation vary between
      geographical areas. Suggestive of a ATTRm amyloidosis are a sensorimotor
      polyneuropathy, positive family history, autonomic dysfunction, cardiomyopathy,
      carpal tunnel syndrome, unexplained weight loss, and resistance to immunotherapy.
      If only sensory A-delta or C fibers are affected, small fiber neuropathy ensues.
      Diagnostic tests for small fiber neuropathy include determination of
      intraepidermal nerve fiber density, laser-evoked potentials, heat- and cold
      detection thresholds, and measurement of the electrochemical skin conductance.
      Therapy currently relies on liver transplantation and TTR-stabilizers (tafamidis,
      diflunisal).

PMID- 30295934
TI  - Response to the comments on 'Continuation of lithium after a diagnosis of chronic
      kidney disease'.

PMID- 30295935
TI  - From molecules to mind: mechanisms of action of electroconvulsive therapy.

PMID- 30295936
TI  - Comment on 'Continuation of lithium after a diagnosis of chronic kidney disease'.

PMID- 30295937
TI  - The RNA editing factor DUA1 is crucial to chloroplast development at low
      temperature in rice.
AB  - Low temperature stress hinders plant growth and chloroplast development and can
      limit the geographic range of cultivars. In rice, japonica cultivars have greater
      chilling tolerance than indica cultivars, but the molecular mechanism underlying
      chilling tolerance is unclear. Here, we report an RNA-binding protein, DUA1,
      cloned from the indica cultivar Dular, which exhibits a deficiency in chloroplast
      development at an early stage of development under low-temperature conditions.
      DUA1 shares high sequence homology with the pentatricopeptide repeat family and
      functions in plastid RNA editing under low-temperature conditions. Our data
      suggest that DUA1 can bind to the plastid-encoded rps8-182 transcript and
      disruption of DUA1 activity impairs editing. The RNA editing cofactor WSP1, a
      partner of DUA1, also participates in chloroplast development at low temperature.
      Western blot analysis indicates that WSP1 enhances DUA1 stability under low
      temperatures. DUA1 sequence analyses of rice core germplasm revealed that three
      major haplotypes of DUA1 and one haplotype showed substantial differences in
      chlorophyll content under low-temperature conditions. Variation at DUA1 may play
      an important role in the adaptation of rice to different growing regions.

PMID- 30295938
TI  - Embolism resistance drives the distribution of Amazonian rainforest tree species
      along hydro-topographic gradients.
AB  - Species distribution is strongly driven by local and global gradients in water
      availability but the underlying mechanisms are not clear. Vulnerability to xylem
      embolism (P50 ) is a key trait that indicates how species cope with drought and
      might explain plant distribution patterns across environmental gradients. Here we
      address its role on species sorting along a hydro-topographical gradient in a
      central Amazonian rainforest and examine its variance at the community scale. We
      measured P50 for 28 tree species, soil properties and estimated the hydrological
      niche of each species using an indicator of distance to the water table (HAND).
      We found a large hydraulic diversity, covering as much as 44% of the global
      angiosperm variation in P50 . We show that P50 : contributes to species
      segregation across a hydro-topographic gradient in the Amazon, and thus to
      species coexistence; is the result of repeated evolutionary adaptation within
      closely related taxa; is associated with species tolerance to P-poor soils,
      suggesting the evolution of a stress-tolerance syndrome to nutrients and drought;
      and is higher for trees in the valleys than uplands. The large observed hydraulic
      diversity and its association with topography has important implications for
      modelling and predicting forest and species resilience to climate change.

PMID- 30295939
TI  - Re: The American Society of Peritoneal Surface Malignancies Multi-Institution
      Evaluation of 1,051 Advanced Ovarian Cancer Patients Undergoing Cytoreductive
      Surgery and HIPEC: An Introduction of the Peritoneal Surface Disease Severity
      Score. Journal of Surgical Oncology 2016;114(7):779-784.

PMID- 30295940
TI  - Re: Increased expression of interleukin-23 associated with progression of
      colorectal cancer. Journal of Surgical Oncology 2017;115(2):208-212.

PMID- 30295941
TI  - Re: The use of supraclavicular free flap with vascularized lymph node transfer
      for treatment of lymphedema: A prospective study of 100 consecutive cases.
      Journal of Surgical Oncology 2017;115(1):68-71.

PMID- 30295942
TI  - Re: Using the 21-gene assay from core needle biopsies to choose neoadjuvant
      therapy for breast cancer: A multicenter trial. Journal of Surgical Oncology
      2017;115(8):917-923.

PMID- 30295943
TI  - Seahorse TLR5 gene responses to Vibrio vulnificus infection, which in combination
      with scuticociliates causes heavy reductions in seahorse aquaculture.

PMID- 30295944
TI  - How Does a Memory Find Its Neurons?

PMID- 30295946
TI  - Intranasal oxytocin in rhesus monkeys alters brain networks that detect social
      salience and reward.
AB  - In primates, resting state functional neuroimaging (rsfcMRI) has identified
      several large-scale, intrinsic brain networks, including the salience network
      (SN), which is involved in detecting stimulus salience. Intranasal oxytocin (IN
      OT) has been shown to modulate the salience and rewarding quality of social
      stimuli in mammals and numerous studies have shown that it can affect the
      functional connectivity between brain regions. Less is known, however, about how
      these effects unfold over time following IN-OT administration. This study used
      rsfcMRI in anesthetized rhesus macaques to track temporal changes in the
      functional connectivity between brain regions involved in the SN, including the
      anterior cingulate cortex (ACC), anterior insula (AI), amygdala (amy), and
      ventral striatum (vstr), lasting 3 hr after IN-OT or Placebo (saline)
      administration. We found significant temporal changes in the functional
      connectivity between all regions associated with treatment condition. IN-OT
      increased the functional connectivity between AI_vstr, ACC_amy (right
      hemisphere), ACC_vstr (left hemisphere), and amy_vstr (right hemisphere), but
      reduced the functional connectivity between ACC_AI, and the AI_amygdala. These
      results suggest that IN-OT may dampen salience detection in rhesus monkeys,
      consistent with previous findings of reduced social vigilance, while enhancing
      the connectivity between the SN and regions involved in processing reward.

PMID- 30295945
TI  - Actinomycin-D and dimethylamino-parthenolide synergism in treating human
      pancreatic cancer cells.
AB  - Preclinical Research & Development Pancreatic cancer is the third leading cause
      of death in the US with a poor 5-year survival rate of 8.5%. A novel anti-cancer
      drug, dimethylamino parthenolide (DMAPT), is the water-soluble analog of the
      natural sesquiterpene lactone, parthenolide. The putative modes of action of
      DMAPT are inhibition of the Nuclear chain factor kappa-light-chain enhancer of
      activated B cells (NFkappaB) pathway and depletion of glutathione levels; the
      latter causing cancer cells to be more susceptible to oxidative stress-induced
      cell death. Actinomycin-D (ActD) is a polypeptide antibiotic that binds to DNA,
      and inhibits RNA and protein synthesis by inhibiting RNA polymerase II. A phase 2
      clinical trial indicated that ActD could be a potent drug against pancreatic
      cancer; however, it was not a favored drug due to toxicity issues. New drug
      entities and methods of drug delivery, used alone or in combination, are needed
      to treat pancreatic cancer more effectively. Thus, it was postulated that
      combining DMAPT and ActD would result in synergistic inhibition of Panc-1
      pancreatic cancer cell growth because DMAPT's inhibition of NFkappaB would
      enhance induction of apoptosis by ActD, via phosphorylation of c-Jun, by
      minimizing NFkappaB inhibition of c-Jun phosphorylation. Combining these two
      drugs induced a higher level of cell death than each drug alone. A fixed drug
      ratio of DMAPT: ActD (1,200:1) was used. Data from metabolic (MTT) and colony
      formation assays were analyzed for synergism with CompuSyn software, which
      utilizes the Chou-Talalay equation. The analyses indicated synergism and moderate
      synergism at combination concentrations of DMAPT/ActD of 12/0.01 and 18/0.015
      MUM, respectively.

PMID- 30295947
TI  - Micro-CT analysis of danger zone thickness in the mesiobuccal roots of maxillary
      first molars.
AB  - AIM: To evaluate dentine thickness from both distal ('danger zone') and mesial
      ('safety zone') aspects of the MB1 and MB2 canals of maxillary first molars at
      the furcation level using micro-CT imaging. METHODOLOGY: One hundred maxillary
      first molars with two canals in the MB root were selected from a Brazilian
      subpopulation and scanned at a resolution of 19.6 MUm in a micro-CT device. From
      each specimen, two axial cross-sectioned images were selected at 2 and 3 mm
      apical to the furcation level of the MB root and evaluated for the smallest
      dentinal thickness. Measurements were made from the outer perimeter of the MB1
      and MB2 canals towards the external root surface from both distal (danger zone)
      and mesial (safety zone) aspects of the root. The influence of an isthmus was
      also considered in the analysis, and samples were classified according to the
      presence or absence of an isthmus in the axial sections. Non-parametric Wilcoxon
      signed-rank tests were used to compare dentinal thickness between MB1 and MB2
      canals with a significant level set at 5%. Colour-coded 3D models of dentine
      thickness throughout the MB root were created and evaluated qualitatively.
      RESULTS: At both levels, median dentine thickness of the MB2 canal was
      significantly lower in both distal and mesial aspects of the root in comparison
      with the MB1 canal (P < 0.01). The presence of an isthmus was not a variable that
      influenced dentinal thickness. Colour-coded models indicated that dentine
      thickness was dependent on the cross-sectional shape of the MB root. At least 50%
      of the sample had <1 mm of dentine thickness at the danger zone of the MB2 canal.
      CONCLUSIONS: Danger zones in the MB roots of maxillary first molars were not
      symmetrical. MB2 canals had less dentine thickness on both aspects of the root
      compared to the MB1 canal.

PMID- 30295948
TI  - Liver fat scores predict liver disease mortality in the United States population.
AB  - BACKGROUND: Fatty liver is a significant global public health burden,
      contributing to premature death. AIM: To examine whether liver fat scores were
      associated with increased overall and disease-specific mortality in a United
      States (US) population-based survey with up to 27 years of linked mortality data.
      METHODS: We studied 9200 fasted viral hepatitis-negative adults in the third
      National Health and Nutrition Examination Survey, 1988-1994. Liver fat was
      predicted using the US fatty liver index (US FLI), fatty liver index (FLI), non
      alcoholic fatty liver disease liver fat score (NAFLD LFS), and hepatic steatosis
      index (HSI). Participants were passively followed up for mortality, identified by
      death certificate underlying or contributing causes, by linkage to National Death
      Index records through 2015. Mortality hazard ratios (HR) were calculated using
      Cox proportional hazards regression to adjust for mortality risk factors.
      RESULTS: During follow-up (median, 23.3 years), cumulative mortality was 31.4%
      overall and 1.1% with liver disease, including primary liver cancer. Elevated
      liver disease mortality was associated with a high US FLI (HR, 5.7; 95%
      confidence interval (CI), 1.3-24.5), and intermediate (HR, 3.1; 95% CI, 1.1-9.1)
      or high (HR, 11.4; 95% CI, 2.9-44.4) NAFLD LFS, but not with a higher FLI or HSI.
      Overall and cardiovascular disease mortality was unassociated with higher liver
      fat scores. CONCLUSIONS: In the US population, a higher US FLI and NAFLD LFS were
      associated with increased liver disease mortality, but not with other mortality
      outcomes. Liver fat scores may be useful for metabolic health surveillance and
      long-term liver disease risk stratification and may complement fibrosis markers
      for tracking.

PMID- 30295949
TI  - Feasibility of photon beam profile deconvolution using a neural network.
AB  - PURPOSE: Ionization chambers are the detectors of choice for photon beam profile
      scanning. However, they introduce significant volume averaging effect (VAE) that
      can artificially broaden the penumbra width by 2-3 mm. The purpose of this study
      was to examine the feasibility of photon beam profile deconvolution (the
      elimination of VAE from ionization chamber-measured beam profiles) using a three
      layer feedforward neural network. METHODS: Transverse beam profiles of photon
      fields between 2 * 2 and 10 * 10 cm2 were collected with both a CC13 ionization
      chamber and an EDGE diode detector on an Elekta Versa HD accelerator. These
      profiles were divided into three datasets (training, validation and test) to
      train and test a three-layer feedforward neural network. A sliding window was
      used to extract input data from the CC13-measured profiles. The neural network
      produced the deconvolved value at the center of the sliding window. The full
      deconvolved profile was obtained after the sliding window was moved over the
      measured profile from end to end. The EDGE-measured beam profiles were used as
      reference for the training, validation, and test. The number of input neurons,
      which equals the sliding window width, and the number of hidden neurons were
      optimized with a parametric sweeping method. A total of 135 neural networks were
      fully trained with the Levenberg-Marquardt backpropagation algorithm. The one
      with the best overall performance on the training and validation dataset was
      selected to test its generalization ability on the test dataset. The agreement
      between the neural network-deconvolved profiles and the EDGE-measured profiles
      was evaluated with two metrics: mean squared error (MSE) and penumbra width
      difference (PWD). RESULTS: Based on the two-dimensional MSE plots, the optimal
      combination of sliding window width of 15 and 5 hidden neurons was selected for
      the final neural network. Excellent agreement was achieved between the neural
      network-deconvolved profiles and the reference profiles in all three datasets.
      After deconvolution, the mean PWD reduced from 2.43 +/- 0.26, 2.44 +/- 0.36, and
      2.46 +/- 0.29 mm to 0.15 +/- 0.15, 0.04 +/- 0.03, and 0.14 +/- 0.09 mm for the
      training, validation, and test dataset, respectively. CONCLUSIONS: We
      demonstrated the feasibility of photon beam profile deconvolution with a
      feedforward neural network in this work. The beam profiles deconvolved with a
      three-layer neural network had excellent agreement with diode-measured profiles.

PMID- 30295950
TI  - Validation and application of a fast Monte Carlo algorithm for assessing the
      clinical impact of approximations in analytical dose calculations for pencil beam
      scanning proton therapy.
AB  - PURPOSE: Monte Carlo (MC) dose calculation is generally superior to analytical
      dose calculation (ADC) used in commercial TPS to model the dose distribution
      especially for heterogeneous sites, such as lung and head/neck patients. The
      purpose of this study was to provide a validated, fast, and open-source MC code,
      MCsquare, to assess the impact of approximations in ADC on clinical pencil beam
      scanning (PBS) plans covering various sites. METHODS: First, MCsquare was
      validated using tissue-mimicking IROC lung phantom measurements as well as
      benchmarked with the general purpose Monte Carlo TOPAS for patient dose
      calculation. Then a comparative analysis between MCsquare and ADC was performed
      for a total of 50 patients with 10 patients per site (including liver, pelvis,
      brain, head-and-neck, and lung). Differences among TOPAS, MCsquare, and ADC were
      evaluated using four dosimetric indices based on the dose-volume histogram
      (target Dmean, D95, homogeneity index, V95), a 3D gamma index analysis (using
      3%/3 mm criteria), and estimations of tumor control probability (TCP). RESULTS:
      Comparison between MCsquare and TOPAS showed less than 1.8% difference for all of
      the dosimetric indices/TCP values and resulted in a 3D gamma index passing rate
      for voxels within the target in excess of 99%. When comparing ADC and MCsquare,
      the variances of all the indices were found to increase as the degree of tissue
      heterogeneity increased. In the case of lung, the D95s for ADC were found to
      differ by as much as 6.5% from the corresponding MCsquare statistic. The median
      gamma index passing rate for voxels within the target volume decreased from 99.3%
      for liver to 75.8% for lung. Resulting TCP differences can be large for lung
      (<=10.5%) and head-and-neck (<=6.2%), while smaller for brain, pelvis and liver
      (<=1.5%). CONCLUSIONS: Given the differences found in the analysis, accurate dose
      calculation algorithms such as Monte Carlo simulations are needed for proton
      therapy, especially for disease sites with high heterogeneity, such as head-and
      neck and lung. The establishment of MCsquare can facilitate patient plan reviews
      at any institution and can potentially provide unbiased comparison in clinical
      trials given its accuracy, speed and open-source availability.

PMID- 30295951
TI  - Estimating onset time from longitudinal data in the presence of measurement error
      with application to estimating gestational age from maternal anthropometry during
      pregnancy.
AB  - Accurate assessment of gestational age at birth is necessary for optimal
      pediatric care. In high resource countries, several methods using ultrasound have
      been proposed to assess gestational age at birth; however, these methods are not
      easily accessible for low-resource populations. We develop a shared random
      parameter model for estimating gestational age at birth from longitudinal
      maternal anthropometry that incorporates additional maternal information from the
      last menstrual period, a measure of gestational age collected with sizable
      measurement error. The proposed methodology is evaluated using simulation studies
      under a training-test set paradigm. In addition, we propose methodology to
      validate prediction when some measurements of the gold standard are collected
      with measurement error. We illustrate the proposed methodologies with data from
      the NICHD Fetal Growth Studies.

PMID- 30295952
TI  - Associations of tumor necrosis factor-alpha polymorphisms with the risk of
      tuberculosis: a meta-analysis.
AB  - Recently, the roles of tumor necrosis factor-alpha (TNF-alpha) polymorphisms in
      tuberculosis (TB) were intensively analyzed, but the results of these studies
      were inconsistent. Therefore, we performed this study to better assess the
      relationship between TNF-alpha polymorphisms and the risk of TB. Eligible studies
      were searched in PubMed, Medline, Embase and CNKI. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were used to assess correlations between TNF-alpha
      polymorphisms and TB. A total of 31 studies were included for analyses.
      Significant associations with the risk of TB were detected for TNF-alpha -308 G/A
      and -857 C/T polymorphisms in overall analyses. Further subgroup analyses based
      on ethnicity of participants revealed that TNF-alpha -238 G/A, -308 G/A, -857 C/T
      and -863 C/A polymorphisms were all significantly associated with the risk of TB
      in East Asians. When we stratified available data according to type of disease,
      we found that TNF-alpha -238 G/A and -308 G/A polymorphisms were significantly
      correlated with the risk of extrapulmonary tuberculosis (EPTB), while the -857
      C/T polymorphism was significantly correlated with the risk of pulmonary
      tuberculosis (PTB). In conclusion, our findings indicated that TNF-alpha -238
      G/A, -308 G/A, -857 C/T and -863 C/A polymorphisms may serve as potential
      biological markers for TB in East Asians. This article is protected by copyright.
      All rights reserved.

PMID- 30295953
TI  - Multistate modeling and simulation of patient trajectories after allogeneic
      hematopoietic stem cell transplantation to inform drug development.
AB  - We present a case study for developing clinical trial scenarios in a complex
      progressive disease with multiple events of interest. The idea is to first
      capture the course of the disease in a multistate Markov model, and then to
      simulate clinical trials from this model, including a variety of hypothesized
      drug effects. This case study focuses on the prevention of graft-versus-host
      disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT).
      The patient trajectory after HSCT is characterized by a complex interplay of
      various events of interest, and there is no established best method of measuring
      and/or analyzing treatment benefits. We characterized patient trajectories by
      means of multistate models that we fitted to a subset of the Center for
      International Blood and Marrow Transplant Research (CIBMTR) database. Events of
      interest included acute GvHD of grade III or IV, severe chronic GvHD, relapse of
      the underlying disease, and death. The transition probability matrix was
      estimated using the Aalen-Johansen estimator, and patient characteristics were
      identified that were associated with different transition rates. In a second
      step, clinical trial scenarios were simulated from the model assuming various
      drug effects on the background transition rates, and the operating
      characteristics of different endpoints and analysis strategies were compared in
      these scenarios. This helped devise a drug development strategy in GvHD
      prevention after allogeneic HSCT. More generally, multistate models provide a
      rich framework for exploring complex progressive diseases, and the availability
      of a corresponding simulation machinery provides great flexibility for clinical
      trial planning.

PMID- 30295954
TI  - Measuring national resilience: A new short version of the scale (NR-13).
AB  - This article is aimed at describing and validating a new short version of the
      National Resilience Scale (NR-13). The available 25-item National Resilience
      Scale has been employed and validated by several studies. However, the present
      data show that it can be substantially shortened without losing either its
      reliability or its validity. The new short version of the scale has been examined
      by the responses of an Israeli sample of adults (N = 1022). Results indicate, as
      expected, that national resilience promoting factors (community resilience and
      sense of coherence) significantly and positively predict NR-13. A resilience
      suppressing factor (sense of danger) negatively and significantly predicts NR-13.
      These predictions have been replicated in an additional sample of Israeli higher
      education students (N = 423). These results support the reliability and the
      validity of the short National Resilience Scale (NR-13).

PMID- 30295955
TI  - Autocalibrated multiband CAIPIRINHA with through-time encoding: Proof of
      principle and application to cardiac tissue phase mapping.
AB  - PURPOSE: In conventional multiband (MB) CAIPIRINHA, additional reference scans
      are acquired to allow the separation of the excited slices. In this study, an
      acquisition-reconstruction technique that makes use of the MB data to calculate
      these reference data is presented. The method was integrated into a 2D time
      resolved phase-contrast MR sequence used to assess velocities of the myocardium.
      METHODS: The RF phases of the MB pulse are cycled through time so that
      consecutive cardiac phases can be grouped to form reference scans at a lower
      temporal resolution. These reference data are subsequently used to separate the
      original slices at the original, high temporal resolution using slice/split-slice
      GRAPPA algorithms. Slice separation performances are evaluated and compared with
      conventional methods at 3 T, and 3 different strategies for the calibration of
      the kernels are proposed and compared. Finally, 6 subjects were scanned to assess
      velocities of the myocardium. RESULTS: Because the acquisition of external
      references is not needed, no additional breath-holds are required and the full MB
      acceleration could be exploited. Because the reference and MB data have the same
      resolution and phase structure, better slice separation was achieved when
      comparing the proposed technique to conventional workflows. Finally, time
      resolved velocities of the myocardial tissue were successfully quantified from MB
      data, showing good agreement with single-band measurements. CONCLUSION: Our built
      in reference method allows the full exploitation of the MB acceleration and it
      limits the number of breath-holds.

PMID- 30295956
TI  - Reactive oxygen species stimulated pulmonary epithelial cells mediate the
      alveolar recruitment of FasL+ killer B cells in LPS-induced acute lung injuries.
AB  - Reactive oxygen species (ROS) are electrophilic chemical species produced from
      incomplete oxidation. They have long been known as aggressive molecules that lead
      to direct tissue and cellular damage. Recent studies have reconsidered ROS as
      second messengers in the initiation and amplification of cell signaling, but how
      ROS regulate lung tissue and immune cell remain unknown. In this study, we used a
      LPS-induced acute lung injury (ALI) mouse model to observe disease, progression
      and determine ROS-related immune responses. We found that ROS play an essential
      pathogenic role in ALI, however, the major role of ROS in exacerbating ALI was
      increasing bronchoalveolar fluid (BALF) B cells rather than eliciting tissue
      damage. Moreover, these pathogenic B cells are FasL+ killer B cells, which
      reported to damage Fas-sensitive target cells including pulmonary epithelial
      cells. Furthermore, via in vitro transwell assays and in vivo treatment with
      neutralizing antibodies. ROS promoted pulmonary epithelial cells to produce CXCL9
      and CXCL10, which recruited B cells into BALF. These results demonstrated that
      during lung injury, instead of causing oxidative damage, ROS mainly serve as
      second messengers, interacting with tissue and immune cells to enhance immune
      responses that lead to more severe disease.

PMID- 30295957
TI  - Visible-Light-Responsive 2D Cadmium-Organic Framework Single Crystals with Dual
      Functions of Water Reduction and Oxidation.
AB  - The development of new metal-organic frameworks (MOFs) with dual functions of
      both water reduction and oxidation under visible-light irradiation is highly
      desirable for promising solar water splitting, but is not yet reported. Herein, a
      cadmium-based MOF (denoted as "Cd-TBAPy") single crystal with a 2D layered
      framework by employing 1,3,6,8-tetrakis(p-benzoic acid)pyrene (H4 TBAPy) as an
      organic linker is reported, which exhibits good visible-light absorption with
      edge of ~600 nm. The Mott-Schottky (M-S) measurement and UV-vis analysis
      integrally reveal that the Cd-TBAPy is an n-type semiconductor with a bandgap of
      ~2.15 eV whose conduction and valence band are estimated to be -0.05 and 2.10 eV,
      respectively. Together with loading of Pt or CoPi cocatalyst, the Cd-TBAPy is
      active for both water reduction and oxidation in the presence of scavengers under
      visible-light irradiation. Especially, the optimized apparent quantum efficiency
      for O2 evolution reaches 5.6% at 420 nm, much higher than that of previous MOF
      based photocatalysts reported so far. This is thought to be the first MOF that
      functions as a photocatalyst for both water reduction and oxidation under visible
      light, demonstrating the intriguing future of MOF materials in solar-to-chemical
      energy conversion.

PMID- 30295958
TI  - The miRNA biogenesis pathway prevents inappropriate expression of injury response
      genes in developing and adult Schwann cells.
AB  - Proper function of the nervous system depends on myelination. In peripheral
      nerves, Schwann cells (SCs) myelinate axons and the miRNA biogenesis pathway is
      required for developmental myelination and myelin maintenance. However,
      regulatory roles of this pathway at different stages of myelination are only
      partially understood. We addressed the requirement of the core miRNA biogenesis
      pathway components Dgcr8, Drosha, and Dicer in developing and adult SCs using
      mouse mutants with a comparative genetics and transcriptomics approach. We found
      that the microprocessor components Dgcr8 and Drosha are crucial for axonal radial
      sorting and to establish correct SC numbers upon myelination. Transcriptome
      analyses revealed a requirement of the microprocessor to prevent aberrantly
      increased expression of injury-response genes. Those genes are predicted targets
      of abundant miRNAs in sciatic nerves (SNs) during developmental myelination. In
      agreement, Dgcr8 and Dicer are required for proper maintenance of the myelinated
      SC state, where abundant miRNAs in adult SNs are predicted to target injury
      response genes. We conclude that the miRNA biogenesis pathway in SCs is crucial
      for preventing inappropriate activity of injury-response genes in developing and
      adult SCs.

PMID- 30295959
TI  - Endoscopic myotomy of Zenker's diverticulum using a novel electrosurgical knife:
      First reported case in the USA.

PMID- 30295960
TI  - Case of endoscopic ultrasonography-guided pancreatic duct rendezvous stenting in
      which initial contrast medium injection was useful for the second puncture.

PMID- 30295961
TI  - Attitudes and Responses of Medical Students and Professional Anatomists to
      Dissecting Different Regions of the Body.
AB  - Although there have been many studies assessing emotional responses of medical
      students to the dissecting room experience, little is known about whether
      dissecting particular regions of the human body cause more concern than others.
      Furthermore, no studies have been conducted on the concerns of professional
      anatomists. In this study, we assessed the hypothesis that medical students are
      more concerned about the dissection of the face, the perineum and the extremities
      of the limbs. We also hypothesized that there are gender differences. For the
      reactions of a group of professional anatomists from the United States and Europe
      we hypothesized that they were less concerned than the medical students and
      showed no differences across the regions of the body. The hypotheses were tested
      by means of questionnaires distributed to medical students at Cardiff University
      and at the Descartes Paris University who had recently completed their anatomy
      courses and to anatomists working at universities in Europe and the USA. Ethical
      approval for the study was obtained from the ethical committees at the Cardiff
      School of Biosciences and at Paris and all data was obtained by consent of the
      respondents and remained confidential. The findings were complex, although the
      level of concern was low overall. Some regional differences were discerned,
      particularly concerning the face, the perineum, the hand and the female chest.
      Anatomists were less concerned than the students and female students and female
      anatomists showed more concern than their male counterparts. Few differences were
      discerned however between student respondents who had positive and neutral
      attitudes to gender "politics" and those who espoused negative views. We
      recommend that, at the start of an anatomy dissection course, time is spent
      dealing with sensitive issues (including equality and diversity issues),
      emotional responses, and matters pertaining to mortality. However, we argue that
      this should not involve hiding regions of the body, nor overreacting to the
      natural anxiety of students, since doing either of these things could enhance
      negative reactions and stifle the progress of the student from being a layperson
      to a competent healthcare professional. Clin. Anat., 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30295963
TI  - A quantitative structure-property relationship (QSPR) for estimating solid
      material-air partition coefficients of organic compounds.
AB  - The material-air partition coefficient (Kma ) is a key parameter to estimate the
      release of chemicals incorporated in solid materials and resulting human
      exposures. Existing correlations to estimate Kma are applicable for a limited
      number of chemical-material combinations without considering the effect of
      temperature. The present study develops a quantitative structure-property
      relationship (QSPR) to predict Kma for a large number of chemical-material
      combinations. We compiled a dataset of 991 measured Kma for 179 chemicals in 22
      consolidated material types. A multiple linear regression model predicts Kma as a
      function of chemical's Koa , enthalpy of vaporization (?Hv ), temperature, and
      material type. The model shows good fitting of the experimental dataset with
      adjusted R2 of 0.93 and has been verified by internal and external validations to
      be robust, stable and has good predicting ability ( Rext2  > 0.78). A generic
      QSPR is also developed to predict Kma from chemical properties and temperature
      only (adjusted R2  = 0.84), without the need to assign a specific material type.
      These QSPRs provide correlation methods to estimate Kma for a wide range of
      organic chemicals and materials, which will facilitate high-throughput estimates
      of human exposures for chemicals in solid materials, particularly building
      materials and furniture.

PMID- 30295962
TI  - Epithelial to mesenchymal transition is involved in ethanol promoted
      hepatocellular carcinoma cells metastasis and stemness.
AB  - Hepatocellular Carcinoma (HCC) is a malignant tumor with high rate of relapse and
      metastasis. Ethanol is a well-known risk factor for HCC; it promotes the
      progression and aggressiveness of HCC. However, the underlying mechanism remains
      unclear. In clinic studies, we showed that alcohol consumption is positively
      correlated with TNM stage and vessel invasion; HCC patients with chronic drinking
      history had faster progression rate and poorer prognosis compared to non
      drinkers. In experimental models, ethanol exposure enhanced the metastasis, and
      invasion of HCC cells. Ethanol exposure increased cancer stem cells (CSC)
      population and enhanced stemness of HCC cells in vitro and in vivo. Mechanically,
      we found that ethanol exposure induced epithelial to mesenchymal transition (EMT)
      through activating Wnt/beta-catenin signaling pathway in HCC cells. We further
      demonstrated that beta-catenin siRNA or salinomycin (an inhibitor of Wnt/beta
      catenin pathway) partially rescued ethanol-induced EMT. In conclusion, this study
      suggested that ethanol exposure promotes the metastasis and stemness of HCC cells
      by inducing EMT.

PMID- 30295964
TI  - Estradiol-regulated innate antiviral responses of human endometrial stromal
      fibroblasts.
AB  - PROBLEM: The contribution of fibroblasts to innate immune protection of the human
      female reproductive tract (FRT) against viral pathogens is relatively unknown.
      METHOD OF STUDY: Endometrial (EM), endocervical (Cx) and ectocervical (ECx)
      fibroblasts were isolated from hysterectomy patients and grown in vitro.
      Fibroblasts were treated with the viral mimic poly (I:C) in the presence or
      absence of the sex hormone estradiol (E2 ), with gene expression measured by real
      time RT-PCR and protein secretion by ELISA. RESULTS: Poly (I:C) induced the
      expression of the interferon-stimulated genes (ISG) MxA, OAS2 and APOBEC3G, and
      the cytokines MCP-1, IL-8, IL-6, CCL20, IFNbeta and RANTES by fibroblasts from
      all three sites. ISG upregulation was dependent upon Type I IFN signaling. E2
      inhibited the poly (I:C)-induced upregulation of MxA and OAS2 in EM fibroblasts,
      but not Cx or ECx fibroblasts. E2 upregulated SDF-1alpha by EM fibroblasts but
      had no effect on secretion of other cytokines either alone or in the presence of
      poly (I:C). Conditioned media (CM) from poly (I:C)-treated or E2 -treated
      fibroblasts significantly reduced HIV infection of CD4+ T cells. CONCLUSION:
      Stromal fibroblasts represent a level of innate immune protection against viral
      pathogens in the FRT beyond that seen with epithelial cells and immune cells. Our
      findings indicate that fibroblasts FRT are selectively responsive to E2 , capable
      of initiating an antiviral response against viral pathogens and may play a role
      in preventing HIV infection of CD4+ T cells.

PMID- 30295966
TI  - Tired and stressed: Examining the need for sleep.
AB  - A key feature of circadian rhythms is the sleep/wake cycle. Sleep causes reduced
      responsiveness to the environment, which puts animals in a particularly
      vulnerable state; yet sleep has been conserved throughout evolution, indicating
      that it fulfils a vital purpose. A core function of sleep across species has not
      been identified, but substantial advances in sleep research have been made in
      recent years using the genetically tractable model organism, Drosophila
      melanogaster. This review describes the universality of sleep, the regulation of
      sleep, and current theories on the function of sleep, highlighting a historical
      and often overlooked theory called the Free Radical Flux Theory of Sleep.
      Additionally, we summarize our recent work with short-sleeping Drosophila mutants
      and other genetic and pharmacological tools for manipulating sleep which supports
      an antioxidant theory of sleep and demonstrates a bi-directional relationship
      between sleep and oxidative stress.

PMID- 30295965
TI  - Risk factors associated with fecal shedding of Listeria monocytogenes by dairy
      cows and calves.
AB  - BACKGROUND: Listeria monocytogenes (LM) is an important foodborne pathogen
      affecting animals and humans. Listeriosis outbreaks in humans caused by
      consumption of unpasteurized dairy products are of serious concern. OBJECTIVE: To
      determine risk factors associated with fecal shedding of LM in family dairy
      farms. ANIMALS: Fecal samples were collected from cows and calves on 20 family
      dairy farms in 2-week intervals for a period of 1 year. METHODS: Longitudinal
      study. LM was detected using qPCR. Univariate mixed effect model and multivariate
      analyses were performed to associate risk factors (dietary change, breed,
      mastitis, other diseases, antibiotic treatment, other treatments, heat index, and
      meteorological season) with fecal shedding of LM. RESULTS: LM was isolated from
      all farms on at least 1 sampling day. The average yearly prevalence was 18.2%
      (98/540) and 8.4% (43/511) in cows and calves, respectively. Heat index (P = .05)
      and meteorological season (P = .04) affected fecal shedding of LM on a farm
      level. Meteorological season only influenced fecal shedding of LM in cows (P =
      .04), whereas heat index (P = .01) influenced fecal shedding of LM in calves.
      Spring season was identified as the major risk factor associated fecal shedding
      of LM on a farm level (P = .01) and in cows (P = .01). Dietary changes were
      associated with lower odds for fecal shedding of LM in calves (P < .01).
      CONCLUSIONS AND CLINICAL IMPORTANCE: Fecal shedding of LM is associated with
      environmental temperatures and the meteorological season. Farmers and
      veterinarians should use this information when implementing strategies to reduce
      risks for LM dissemination in animals and in the community.

PMID- 30295967
TI  - Photophysical Pathways in Highly Sensitive Cs2 AgBiBr6 Double-Perovskite Single
      Crystal X-Ray Detectors.
AB  - The sensitive detection of X-rays embodies an important research area, being
      motivated by a common desire to minimize the radiation doses required for
      detection. Among metal halide perovskites, the double-perovskite Cs2 AgBiBr6
      system has emerged as a promising candidate for the detection of X-rays, capable
      of high X-ray stability and sensitivity (105 MUC Gy-1 cm-2 ). Herein, the
      important photophysical pathways in single-crystal Cs2 AgBiBr6 are detailed at
      both room (RT) and liquid-nitrogen (LN2 T) temperatures, with emphasis made
      toward understanding the carrier dynamics that influence X-ray sensitivity. This
      study draws upon several optical probes and an RT excitation model is developed
      which is far from optimal, being plagued by a large trap density and fast free
      carrier recombination pathways. Substantially improved operating conditions are
      revealed at 77 K, with a long fundamental carrier lifetime (>1.5 us) and a marked
      depopulation of parasitic recombination pathways. The temperature dependence of a
      single-crystal Cs2 AgBiBr6 X-ray detecting device is characterized and a strong
      and monotonic enhancement to the X-ray sensitivity upon cooling is demonstrated,
      moving from 316 MUC Gy-1 cm-2 at RT to 988 MUC Gy-1 cm-2 near LN2 T. It is
      concluded that even modest cooling-via a Peltier device-will facilitate a
      substantial enhancement in device performance, ultimately lowering the radiation
      doses required.

PMID- 30295969
TI  - FIP4/Arfophilin-2 plays overlapping but distinct roles from FIP3/Arfophilin-1 in
      neuronal migration during cortical layer formation.
AB  - The class II Rab11 family-interacting proteins, FIP3 and FIP4, also termed
      Arfophilin-1 and Arfophilin-2, respectively, are endosomal proteins that function
      as dual effector proteins for Rab11 and ADP ribosylation factor (Arf) small
      GTPases. In the present study, we examined the expression and role of FIP4 in
      neuronal migration during cerebral layer formation. FIP4 mRNA was first weakly
      detected in post-mitotic migrating neurons in the upper intermediate zone, and
      expression was markedly increased in the cortical layer. Exogenously expressed
      FIP4 protein was localized to subpopulations of EEA1- and syntaxin 12-positive
      endosomes in migrating neurons, and was partially colocalized with FIP3.
      Knockdown of FIP4 by in utero electroporation significantly stalled transfected
      neurons in the lower cortical layer and decreased the speed of neuronal migration
      in the upper intermediate zone and in the cortical plate compared with control
      small hairpin RNA (shRNA)-transfected neurons. Furthermore, co-transfection of
      shRNA-resistant wild-type FIP4, but not wild type FIP3 or FIP4 mutants lacking
      the binding region for Rab11 or Arf, significantly improved the disturbed
      cortical layer formation caused by FIP4 knockdown. Collectively, our findings
      suggest that FIP4 and FIP3 play overlapping but distinct roles in neuronal
      migration downstream of Arf and Rab11 during cortical layer formation.

PMID- 30295968
TI  - Efficient access to both enantiomers of 3-(1-hydroxyethyl)phenol by
      regioselective and enantioselective CAL-B-catalyzed hydrolysis of diacetate in
      organic media by sodium carbonate.
AB  - In the present paper, we describe several pathways employing immobilized lipase
      from Candida antarctica B (CAL-B) as biocatalyst to prepare easily both
      enantiomers of 3-(1-hydroxyethyl)phenol. We have applied hydrolysis with Na2 CO3
      in organic media under mild conditions. The reaction parameters solvent effect,
      amount of lipase, and Na2 CO3 were examined with 3-(1-acetoxyethyl)phenyl acetate
      as substrate. In alkaline hydrolysis, (R)-3-(1-hydroxyethyl)phenol was obtained
      with ee = 99% and (S)-(-)-3-(1-acetoxyethyl)phenol with ee = 98% at optimal
      conversion (c = 50%) and high selectivity (E > 200). Two other deacylation
      reactions were compared: alcoholysis with MeOH and with NEt3 . The acylation of 3
      (1-hydroxyethyl)phenol with vinyl acetate was also examined. Alkaline hydrolysis
      gave the best results, while good regioselectivity and enantioselectivity were
      observed in alcoholysis and acylation reactions. Finally, (S)- and (R)-3-(1
      hydroxyethyl)phenol (ee > 98%), key intermediates for the synthesis of important
      drugs, were prepared from the corresponding racemic diacetate through alkaline
      hydrolysis.

PMID- 30295970
TI  - Work pattern of neurology nurses in a Chinese hospital: A time and motion study.
AB  - AIM: To investigate nursing work patterns in a neurology department in a Chinese
      hospital. BACKGROUND: Knowledge of nursing work patterns is important for nursing
      management and work design, and for the evaluation of organizational process
      change associated with the introduction of an innovation. METHODS: A time-and
      motion method was used to observe 14 registered nurses' (RNs') work patterns in a
      neurology department in a Chinese hospital. RESULTS: There were 147 hr of
      observation. Overall, the most time-consuming activities were verbal
      communication (28.5%) and documentation (28.3%), followed by indirect care
      (14.6%) and direct care (14%). Compared to support RNs, charge RNs spent 20% more
      time on documentation and 11% more time on verbal communication. Two-thirds of
      the observed activities had a duration of less than 40 s. CONCLUSIONS:
      Communication, in verbal and written forms, consumed more than half of the
      nursing time. Conversely, nurses only spent about a quarter of their worktime on
      preparation for care provision and direct care provision. This reflects the
      significant role and resource-consuming nature of communication to provide safe
      and quality care. IMPLICATIONS FOR NURSING MANAGEMENT: Communication methods need
      to be enhanced to improve nursing productivity. This may be achieved through the
      introduction of more effective nursing documentation methods.

PMID- 30295971
TI  - Accessory tricuspid leaflet associated with persistent left superior vena cava.
AB  - Right atrioventricular valve is historically named as tricuspid valve. However,
      cases depicting multi-leaflet morphology of the right atrioventricular valve were
      reported. Accessory leaflet of the tricuspid valve is a rare entity and
      associated with congenital cardiac anomalies. We present an accessory tricuspid
      valve in a patient with isolated persistent left superior vena cava.

PMID- 30295972
TI  - Speckle tracking echocardiography and right ventricle dysfunction in acute
      respiratory distress syndrome a pilot study.
AB  - PURPOSE: Speckle tracking echocardiography is a novel echocardiographic technique
      to assess RV myocardial function but no data are so far available in patients
      with acute respiratory distress syndrome (ARDS), and we aimed at assessing the
      feasibility of 2 dimensional (2D) speckle tracking echocardiography and the
      prognostic role of RV free wall speckle tracking strain in 30 consecutive
      patients with moderate-severe ARDS MATERIALS AND METHODS: In an observational
      prospective study, 30 consecutive patients with moderate-severe ARDS were
      enrolled. Echocardiography was performed within 12 hours from ICU admission.
      RESULTS: Mortality rate was 33% (10/30). Non-survivors showed lower values of pH
      (7.32 +/- 0.09, P = 0.03) and higher troponin I levels (0.32 (0.08-0.46), P =
      0.04), NT-pro BNP (3091 (2662-7128), P = 0.009), and SAPS II (60.3 +/- 9.6, P <
      0.001). At echocardiographic examination, non-survivors showed lower values of
      TAPSE (18.3 +/- 3, P = 0.034) and higher systolic pulmonary arterial pressure
      (49.6 +/- 16, P = 0.05). Two patients (6.6%) did not show valid acoustic windows.
      Only three patients showed normal values of RV strain free wall (22%, 25%, and
      28% absolute values, respectively), among whom one patient died. When compared to
      survivors, non-survivors showed significantly lower values of RV strain free wall
      (-10.4 +/- 0.10, P < 0.001). CONCLUSIONS: In mechanically ventilated moderate
      severe ARDS, 2D speckle tracking is feasible even though difficult acoustic
      windows are common. Further studies are needed to confirm our findings in a
      larger cohort of patients.

PMID- 30295974
TI  - E3 ubiquitin ligases LNX1 and LNX2 localize at neuronal gap junctions formed by
      connexin36 in rodent brain and molecularly interact with connexin36.
AB  - Electrical synapses in the mammalian central nervous system (CNS) are
      increasingly recognized as highly complex structures for mediation of neuronal
      communication, both with respect to their capacity for dynamic short- and long
      term modification in efficacy of synaptic transmission and their multimolecular
      regulatory and structural components. These two characteristics are inextricably
      linked, such that understanding of mechanisms that contribute to electrical
      synaptic plasticity requires knowledge of the molecular composition of electrical
      synapses and the functions of proteins associated with these synapses. Here, we
      provide evidence that the key component of gap junctions that form the majority
      of electrical synapses in the mammalian CNS, namely connexin36 (Cx36), directly
      interacts with the related E3 ubiquitin ligase proteins Ligand of NUMB protein X1
      (LNX1) and Ligand of NUMB protein X2 (LNX2). This is based on immunofluorescence
      colocalization of LNX1 and LNX2 with Cx36-containing gap junctions in adult mouse
      brain versus lack of such coassociation in LNX null mice, coimmunoprecipitation
      of LNX proteins with Cx36, and pull-down of Cx36 with the second PDZ domain of
      LNX1 and LNX2. Furthermore, cotransfection of cultured cells with Cx36 and E3
      ubiquitin ligase-competent LNX1 and LNX2 isoforms led to loss of Cx36-containing
      gap junctions between cells, whereas these junctions persisted following
      transfection with isoforms of these proteins that lack ligase activity. Our
      results suggest that a LNX protein mediates ubiquitination of Cx36 at neuronal
      gap junctions, with consequent Cx36 internalization, and may thereby contribute
      to intracellular mechanisms that govern the recently identified modifiability of
      synaptic transmission at electrical synapses.

PMID- 30295975
TI  - Early (90-day) mortality after radical radiotherapy for head and neck squamous
      cell carcinoma: A population-based analysis.
AB  - BACKGROUND: A retrospective, population-based analysis of 90-day mortality in
      patients with squamous cell carcinoma of the head and neck treated with
      radiotherapy was performed to determine the early mortality rate and associated
      risk factors. METHODS: Data were abstracted for all consecutive patients with
      cancer of the head and neck treated from 1998 to 2014 at the BC Cancer Agency
      with curative intent radiotherapy (n = 5658). Logistic regression analysis was
      used to determine factors associated with early mortality. RESULTS: The median
      age at diagnosis was 63 years. The mortality rate at 90 days after starting
      radiotherapy (RT) was 3.6% (n = 203/5658). The cause of death was attributed to
      head and neck cancer for 81% of patients. Multivariate analysis demonstrated that
      increasing age, oral cavity subsite, and advanced T and N classification were
      associated with an increased risk of early mortality (p < .05). CONCLUSIONS: The
      risk of early mortality was 3.6%. Elderly patients with advanced T and N
      classification had the highest risk of early mortality.

PMID- 30295977
TI  - What is the added value of the waist-to-hip ratio on top of the BIOSTAT risk
      prediction model in patients with heart failure? Reply.

PMID- 30295976
TI  - Copper-Catalyzed Radical Cross-Coupling of Redox-Active Oxime Esters, Styrenes,
      and Boronic Acids.
AB  - A visible-light-driven, copper-catalyzed three-component radical cross-coupling
      of oxime esters, styrenes, and boronic acids has been developed. Key steps of
      this protocol involve catalytic generation of an iminyl radical from a redox
      active oxime ester and subsequent C-C bond cleavage to generate a cyanoalkyl
      radical. Upon its addition to styrene, the newly formed benzylic radical
      undergoes coupling with a boronic-acid-derived ArCuII complex to achieve 1,1
      diarylmethane-containing alkylnitriles.

PMID- 30295973
TI  - Associations of maternal immune response with MeHg exposure at 28 weeks'
      gestation in the Seychelles Child Development Study.
AB  - PROBLEM: Maternal methylmercury (MeHg) exposure may be associated with immune
      response during pregnancy. METHOD OF STUDY: In the high fish-eating Seychelles
      Child Development Study Nutrition Cohort 2, we examined the association between
      maternal MeHg, polyunsaturated fatty acids (PUFA), and immune markers (Th1:Th2;
      TNF-alpha, IL-1beta, IFN-gamma, IL-2, IL-4, IL-5, IL-10, MCP-1, TARC, sFlt-1,
      VEGF-D, CRP and IL-6) at 28 weeks' gestation. Linear regression examined
      associations between MeHg exposure and immune markers with and without adjustment
      for PUFA. RESULTS: In all models, as MeHg concentrations increased, the Th1:Th2
      ratio, total Th1 and individual Th1 (IL-1beta, IL-2, TNF-alpha) concentrations
      decreased. MeHg was not associated with total Th2 cytokines but was associated
      with a decrease in IL-4 and IL-10. MeHg was positively associated with TARC and
      VEGF-D and negatively associated with CRP. There was a significant interaction
      between MeHg and the n-6:n-3 ratio, with MeHg associated with a larger decrease
      in Th1:Th2 at higher n-6:n-3 PUFA ratios. The n-3 PUFA were associated with lower
      CRP, IL-4 and higher IFN-gamma. The n-6 PUFA were associated with higher IL
      1beta, IL-2, TNF-alpha, IL-4, IL-10, CRP and IL-6. CONCLUSION: Maternal MeHg was
      associated with markers of immune function at 28 weeks' gestation. A significant
      interaction between MeHg and the n-6:n-3 ratio on the Th1:Th2 ratio suggests that
      the n-3 PUFA may mitigate any immunosuppressive associations of MeHg. The n-3 and
      n-6 PUFA were associated with suppressive and stimulatory immune responses,
      respectively. Overall, the associations were of small magnitude, and further
      research is required to determine the clinical significance.

PMID- 30295978
TI  - Talking to patients with heart failure about end of life.

PMID- 30295979
TI  - Gliosarcoma: Neuroimaging and Immunohistochemical Findings.
AB  - BACKGROUND AND PURPOSE: Gliosarcoma (GSC) is an intra-axial lesion which often
      abuts a dural margin and is composed of glial and mesenchymal elements. This
      lesion is considered a variant of isocitrate dehydrogenase (IDH)-wild type
      glioblastoma (GBM). The purpose of this study is to evaluate the imaging and
      molecular features of GSC in a large patient cohort. METHODS: Pathology-proved
      GSC cases were collected from our quaternary care center spanning the last 16
      years and IDH status was documented. Older GSC cases without prior
      immunohistochemical testing underwent tissue block staining to obtain IDH status.
      When available, p53, phosphate and tensin (PTEN), MIB-1, EGFR amplification, and
      MGMT methylation were recorded and imaging findings tabulated. Logistic
      regression analyses were performed to determine correlation of molecular markers
      and imaging characteristics. RESULTS: A total of 25 cases were identified (21 de
      novo, 4 post-treatment). All lesions contacted a dural, pial, or ependymal
      surface and were negative for an IDH R132H mutation, including postradiation GSC.
      In total, 16 of 16 cases showed nonamplification of EGFR/CEP7, 2 of 16
      demonstrated MGMT methylation, and multiple lesions demonstrated p53 and PTEN
      mutations. Imaging features included areas of nodular thickening in necrotic
      lesions which appeared to abut the site of dural contact. There was no
      significant correlation of molecular markers with imaging characteristics.
      CONCLUSION: GSC was IDH(-) in all cases, supporting the current understanding of
      this lesion being a wild-type GBM variant. Additional molecular markers
      demonstrated no significant correlation with imaging findings in this cohort.

PMID- 30295980
TI  - Assessing the methodological quality of the Canadian Psychiatric Association's
      anxiety and depression clinical practice guidelines.
AB  - RATIONALE, AIMS, AND OBJECTIVES: Clinical practice guidelines (CPGs) endeavour to
      incorporate the best available research evidence together with the clinically
      informed opinions of leading experts in order to guide clinical practice when
      dealing with a given condition. There has been increased interest in CPGs that
      are evidence based and that promote best practice, a central component of which
      is incorporating the best available research predicated on strong study designs.
      Despite this soaring interest, there remains heterogeneity in the methodological
      quality of many CPGs, which may have an effect on the quality of services that
      clinicians offer. In light of this, this study examined the quality of the
      methodology used to develop two CPGs of the Canadian Psychiatric Association
      (CPA). METHOD: The CPA's guidelines for the management of anxiety disorders
      (2006) and for the treatment of depressive disorders (2001) were assessed by
      trained raters using the Appraisal of Guidelines for Research and Evaluation II
      Instrument scale. RESULTS: The blind ratings of three trained raters demonstrated
      that the anxiety and depression CPGs had a number of strengths and important
      weaknesses. CONCLUSION: Implications for the development of future CPGs on
      anxiety and depression, including recommendations to improve guideline quality in
      psychiatry in particular, are discussed.

PMID- 30295982
TI  - The NIA interventions testing program announces the 2016 solicitation of
      proposals.
AB  - THE NIA INTERVENTIONS TESTING PROGRAM ENCOURAGES PARTICIPATION BY THE RESEARCH
      COMMUNITY THOUGH ITS ANNUAL CALL-FOR-PROPOSALS. THIS SHORT TAKE SERVES AS A BRIEF
      INTRODUCTION TO THE PROGRAM AND ANNOUNCEMENT FOR THE NEXT PROPOSAL RECEIPT DATE.

PMID- 30295981
TI  - Hydrogen Atom Transfer Reactions via Photoredox Catalyzed Chlorine Atom
      Generation.
AB  - The selective functionalization of chemically inert C-H bonds remains to be fully
      realized in achieving organic transformations that are redox-neutral, waste
      limiting, and atom-economical. The catalytic generation of chlorine atoms from
      chloride ions is one of the most challenging redox processes, where the
      requirement of harsh and oxidizing reaction conditions renders it seldom utilized
      in synthetic applications. We report the mild, controlled, and catalytic
      generation of chlorine atoms as a new opportunity for access to a wide variety of
      hydrogen atom transfer (HAT) reactions owing to the high stability of HCl. The
      discovery of the photoredox mediated generation of chlorine atoms with Ir-based
      polypyridyl complex, [Ir(dF(CF3 )ppy)2 (dtbbpy)]Cl, under blue LED irradiation is
      reported.

PMID- 30295983
TI  - Palladium-Catalyzed Intermolecular Arylcarbonylation of Unactivated Alkenes:
      Incorporation of Bulky Aryl Groups at Room Temperature.
AB  - A palladium-catalyzed intermolecular arylcarbonylation of unactivated alkenes has
      been developed. Unsymmetrical diaryliodonium salts (DAISs) were used as arylation
      reagents, the bulky aryl group (ArL ) of which was exclusively incorporated into
      the arylcarbonylated products, which contained the ArL group and a carboxylic
      ester group at the alpha- and beta-carbon position, respectively, of the original
      terminal C-C double bond. The reaction features excellent chemo- and
      regioselectivity, high functional-group tolerance, and very mild reaction
      conditions.

PMID- 30295984
TI  - Special Issue: Materials Research in Israel.

PMID- 30295985
TI  - Constructing Universal Ionic Sieves via Alignment of Two-Dimensional Covalent
      Organic Frameworks (COFs).
AB  - The shuttle effect of electrode materials always leads to capacity loss and poor
      cycle life of batteries. Two-dimensional (2D) covalent organic frameworks (COFs)
      with uniform and controllable nanopores provide a promising strategy for
      fabricating ionic sieves to inhibit the shuttle effect. However, the insoluble
      nature of COFs made it difficult to fabricate compact and ordered membranes of
      COFs. Herein, we report a novel method for facilely anisotropic ordering of 2D
      COFs via depositing COFs onto graphene. The resulted double-layer membranes
      acting as ionic sieves impressively inhibit the shuttle effect and exhibit
      versatility to both organic sodium-ion batteries and Li-S batteries, leading to
      high cyclability.

PMID- 30295987
TI  - MRI-Guided High-Intensity Focused Ultrasound as an Emerging Therapy for Stroke: A
      Review.
AB  - Stroke, either ischemic or hemorrhagic, accounts for significantly high morbidity
      and mortality rates around the globe effecting millions of lives annually. For
      the past few decades, ultrasound has been extensively investigated to promote
      clot lysis for the treatment of stroke, myocardial infarction, and acute
      peripheral arterial occlusions, with or without the use of tPA or contrast
      agents. In the age of modern minimal invasive techniques, magnetic resonance
      imaging-guided high-intensity focused ultrasound is a new emerging modality that
      seems to promise therapeutic utilities for both ischemic and hemorrhagic stroke.
      High-intensity focused ultrasound causes thermal heating as the tissue absorbs
      the mechanical energy transmitted by the ultrasonic waves leading to tissue
      denaturation and coagulation. Several in-vitro and in-vivo studies have
      demonstrated the viability of this technology for sonothrombolysis in both types
      of stroke and have warranted clinical trials. Apart from safety and efficacy,
      initiation of trials would further enable answers regarding its practical
      application in a clinical setup. Though this technology has been under study for
      treatment of various brain diseases for some decades now, relatively very few
      neurologists and even neurosurgeons seem to be acquainted with it. The aim of
      this review is to provide basic understanding of this powerful technology and
      discuss its clinical application and potential role as an emerging viable
      therapeutic option for the future management of stroke.

PMID- 30295989
TI  - Plasmacytoma variant translocation 1 (PVT1) regulates trophoblast viability,
      proliferation, and migration and is downregulated in spontaneous abortion.
AB  - PROBLEM: Human pregnancy is a complex biological process, and spontaneous
      abortion is the most common complication of pregnancy. LncRNAs have been
      identified that play key roles in a variety of human diseases. Recently,
      lncRNAPVT1 was reported to relate to the pathogenesis and progression of
      pregnancy. However, the role and underlying mechanism of PVT1 in trophoblast cell
      dysfunction in spontaneous abortion remain largely unknown. METHOD OF STUDY: The
      effects of PVT1, miR-424, and eIF5A on HTR8 cells and human villi tissues from
      spontaneous or induced abortions were investigated using CCK-8 assay, EdU assay,
      real-time polymerase chain reaction, Western blotting, cell transfection assays,
      cell migration assays, and luciferase reporter gene assays. RESULTS:
      Overexpression of PVT1 promoted HTR8 cell viability, proliferation, and
      migration. Suppression of PVT1 promoted miR-424 expression, and miR-424 could
      modulate the effects of PVT1 in HTR8 cells. MiR-424 exerted its function via
      regulation of eIF5A expression in HTR8 cells. PVT1 and eIF5A expression were
      decreased and miR-424 was increased in clinical samples from spontaneous
      abortion, compared to samples from elective induced abortion. CONCLUSION: PVT1
      regulates trophoblast cell function via modulation of a PVT1/miR-424/eIF5A
      pathway.

PMID- 30295990
TI  - Fluorescence Imaging of Alzheimer's Disease with a Flat Ensemble Formed between a
      Quinoline-Malononitrile AIEgen and Thin-Layer Molybdenum Disulfide.
AB  - The sensitive imaging of amyloid-beta (Abeta) peptides is important for the
      timely detection of neurodegenerative diseases, such as Alzheimer's disease (AD).
      Although clinically the diagnosis of AD relies on the use of radiolabeled imaging
      reagents, herein we report the simple construction of a "flat ensemble" formed
      between a quinoline-malononitrile AIEgen (EDS) and thin-layer molybdenum
      disulfide (2D MoS2 ) for the sensitive detection of Abeta by means of
      fluorescence-based techniques. Self-assembly between EDS and 2D MoS2 in aqueous
      buffer solution produces the flat ensemble, and the subsequent interaction of the
      material ensemble with oligomeric and aggregated Abeta peptides leads to up to 19
      fold enhanced fluorescence of EDS. The ensemble is also applicable for staining
      Abeta aggregates in vivo.

PMID- 30295986
TI  - Identification of Novel Gata3 Distal Enhancers Active in Mouse Embryonic Lens.
AB  - BACKGROUND: The tissue-specific transcriptional programs during normal
      development require tight control by distal cis-regulatory elements, such as
      enhancers, with specific DNA sequences recognized by transcription factors,
      coactivators, and chromatin remodeling enzymes. Gata3 is a sequence-specific DNA
      binding transcription factor that regulates formation of multiple tissues and
      organs, including inner ear, lens, mammary gland, T-cells, urogenital system, and
      thyroid gland. In the eye, Gata3 has a highly restricted expression domain in the
      posterior part of the lens vesicle; however, the underlying regulatory mechanisms
      are unknown. RESULTS: Here we describe the identification of a novel bipartite
      Gata3 lens-specific enhancer located ~18 kb upstream from its transcriptional
      start site. We also found that a 5-kb Gata3 promoter possesses low activity in
      the lens. The bipartite enhancer contains arrays of AP-1, Ets-, and Smad1/5
      binding sites as well as binding sites for lens-associated DNA-binding factors.
      Transient transfection studies of the promoter with the bipartite enhancer showed
      enhanced activation by BMP4 and FGF2. CONCLUSIONS: These studies identify a novel
      distal enhancer of Gata3 with high activity in lens and indicate that BMP and FGF
      signaling can up-regulate expression of Gata3 in differentiating lens fiber cells
      through the identified Gata3 enhancer and promoter elements. Developmental
      Dynamics 247:1186-1198, 2018. (c) 2018 The Authors. Developmental Dynamics
      published by Wiley Periodicals, Inc. on behalf of American Association of
      Anatomists.

PMID- 30295988
TI  - Influence of lack of posterior occlusal support on cognitive decline among 80
      year-old Japanese people in a 3-year prospective study.
AB  - AIM: Previous studies have reported significant associations between tooth loss
      or periodontal status and cognitive function; however, animal experimental
      studies have shown that occlusion might be a more important factor in cognitive
      decline. The purpose of the present study was to investigate the influence of a
      lack of posterior occlusal support by residual teeth on the decline of cognitive
      function over a 3-year period among 80-year-old Japanese people. METHODS:
      Participants were community-dwelling older adults (n = 515, age 79-81 years).
      Cognitive function was measured using the Japanese version of the Montreal
      Cognitive Assessment. At baseline, participants were divided into two groups:
      those with and without posterior occlusal support. Participants whose Japanese
      version of the Montreal Cognitive Assessment score decreased by >=3 points over
      the 3-year period were defined as the declined group. Logistic regression was
      carried out for the decline in Japanese version of the Montreal Cognitive
      Assessment scores, including dental status and possible risk factors as
      independent variables. RESULTS: More participants without posterior occlusal
      support tended to be in the cognitive decline group (49.4%) than in the
      maintained group (38.5%; chi2 -test, P = 0.02). Logistic regression analysis
      showed that a lack of posterior occlusal support was a significant variable (odds
      ratio 1.55, P = 0.03) for cognitive decline, even after adjusting for other risk
      factors. However, the number of teeth or mean periodontal pocket depth was not
      significantly correlated with cognitive decline. CONCLUSIONS: The present
      findings suggest that a lack of posterior occlusal support predicted the
      incidence of cognitive decline, even after adjusting for possible risk factors in
      community-dwelling old-old people. Geriatr Gerontol Int 2018; 18: 1439-1446.

PMID- 30295991
TI  - In Vivo Synthesis of Nanocomposites Using the Recombinant Escherichia coli.
AB  - Biogenic gold nanorod (AuNR)-Ag core-shell nanocomposites (NCs) are synthesized
      by using recombinant Escherichia coli to demonstrate in vivo synthesis of
      biogenic NCs for the first time. The chemically synthesized AuNRs are
      internalized into the E. coli, and Ag ions are reduced and grown on the surface
      of the AuNRs with the assistance of metal-binding proteins, producing biogenic
      core-shell AuNR-Ag NCs. The core-shell structure of the biogenic AuNR-Ag NC is
      confirmed by transmission electron microscopy and energy-dispersive X-ray
      analysis. The biogenic AuNR-Ag NCs exhibit good plasmonic effects. While the core
      shell morphology of the AuNR and Ag NCs is due to the similar lattice of Au and
      Ag, the shape of the biogenic NCs composed of gold nanoparticles and Fe is
      aciniform, and that of Fe3 O4 NPs and Au/Ag is a network structure, demonstrating
      the controllability of biogenic nanosynthesis using diverse metal combinations
      with different NC morphologies.

PMID- 30295992
TI  - Osteoclastogenesis Inhibitory Polyketides from the Sponge-Associated Fungus
      Xylaria feejeensis.
AB  - A new ten-membered macrolide (1) and a new alpha-pyrone derivative, (-)-annularin
      C (2), together with 14 known analogs (3-16) were isolated from the AcOEt extract
      of the fungus Xylaria feejeensis isolated from the South China Sea sponge
      Stylissa massa. The structures of the new compounds were elucidated by the
      spectroscopic analysis and by comparison with reported data. The absolute
      configuration was determined by the optical rotation and ECD experiments. In an
      in vitro test, compounds 1, 5 and 9 exhibited significant down-regulating
      activity of osteoclast cell differentiation at 0.5 and 1 MUm. This is the first
      report of the fungus X. feejeensis from a marine sponge and of osteoclastogenesis
      inhibitory activity for the metabolites of these kinds.

PMID- 30295994
TI  - Noninvasive evaluation of the correlation between thickness of the buccal bone
      and attached gingiva of maxillary premolars.
AB  - OBJECTIVE: To noninvasively determine the relationship between the thickness of
      the buccal bone and attached gingiva of the maxillary premolars. MATERIAL AND
      METHODS: 128 maxillary premolars in 32 patients were assessed for measurement of
      buccal bone thickness and corresponding attached gingival thickness at 3 mm
      apical to cemento-enamel junction. Buccal bone thickness was measured on cone
      beam computed tomography scans and attached gingival thickness by ultrasound
      unit. Pearson's correlation coefficient was calculated to assess the correlation
      between buccal bone and attached gingival thickness at each tooth type. RESULTS:
      The mean buccal bone thickness at the maxillary premolars was 1.07 mm. The 1st
      premolars had a buccal bone thickness < 1 mm at 68% of all sites, and the 2nd
      premolars had a buccal bone thickness of 1.0-2.0 mm at 32% of all sites. The 1st
      premolars had a gingival thickness > 1.2 mm at 55% of all sites, and the 2nd
      premolars had a gingival thickness of 1.1-1.3 mm at 45% of all sites. The
      correlation between buccal bone and attached gingival thickness was moderately
      positive (r = 0.406; P < .001). CONCLUSIONS: The relationship between buccal bone
      thickness and gingival thickness is independent of each other in the maxillary
      right first premolar, whereas a moderate correlation with a dependent relation
      exists in the maxillary right second premolar, maxillary left first premolar, and
      maxillary left second premolar. CLINICAL SIGNIFICANCE: Soft tissue and hard
      tissue associated with volumetric changes in maxillary premolar region can be
      unfavorable for both aesthetic and implant placement. In fact this study
      highlighted the relationship between the thickness of attached gingiva and
      corresponding buccal bone in maxillary premolar region so to enable for proper
      planning of implant therapy following extraction.

PMID- 30295993
TI  - A comparative study of resveratrol and resveratrol-functional selenium
      nanoparticles: Inhibiting amyloid beta aggregation and reactive oxygen species
      formation properties.
AB  - Deposition of amyloid-beta (Abeta) aggregates and formation of neurotoxic
      reactive oxygen species (ROS) are significant pathological signatures of
      Alzheimer's disease (AD). Resveratrol (Res) is an antioxidant with the potential
      to treat AD. However, the bioavailability and solubility of Res is very low and
      it cannot entirely inhibit Cu2+ -induced Abeta42 aggregation at low
      concentration. Herein, we combine the unique Abeta absorption property of
      selenium nanoparticles with the natural antioxidant agent Res to form Res@SeNPs.
      Our in vitro biological evaluation revealed that modification of Res with SeNPs
      provides a synergistic effect on Cu2+ -induced Abeta42 aggregation, ROS
      generation and, more importantly, protects PC12 cells from Abeta42-Cu2+ complexes
      induced cell death. It is believed that SeNPs can improve the application of Res
      in AD treatment as Res@SeNPs is more efficient than Res in reducing Abeta42
      toxicity in long-term use. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part A: 106A: 3034-3041, 2018.

PMID- 30295995
TI  - Hyperkeratosis of the nipple and areola: a histopathologic pitfall.

PMID- 30295996
TI  - Effect of mouthguard design on retention and potential issues arising with
      usability in sport.
AB  - BACKGROUND/AIMS: Mouthguard retention could potentially increase an athlete's
      motivation to wear the device, due to potential improvements in physical comfort.
      The aim of this study was to examine the retentive properties of selected
      customised mouthguard designs, during normal conditions (dry) and within the
      presence of artificial saliva (wet). Additionally, the correlation between
      thickness and retention was investigated. MATERIAL AND METHODS: Six different
      custom mouthguard designs (MG1-MG6) reported in previous studies, were pressure
      formed with 2 and 4 mm blanks accordingly. Thickness was measured 10 times at
      seven anatomical points and the mean (+/-SD) was recorded. A novel rig was
      fabricated to connect the mouthguards to a Hounsfield H10KS Tensometer, which was
      used to fully displace each device from the model at a constant rate of 50
      mm/min. The test was repeated under both dry and wet conditions. RESULTS:
      Retention forces recorded at the anterior region demonstrated higher measurements
      under wet conditions than dry (P < 0.001). The total retention of the mouthguards
      was influenced by alterations in their design. Trend analysis indicated that 64%
      of MG retention could be explained by their thickness under dry conditions and
      55% when wet. CONCLUSIONS: Design and thickness of mouthguards are key factors in
      retention. Mouthguard fabrication techniques should be considered in order to
      minimize dislodgment of the devices as well as potentially increasing the
      wearability of mouthguards during sport.

PMID- 30295997
TI  - A sulfonated reversible thermal gel for the spatiotemporal control of VEGF
      delivery to promote therapeutic angiogenesis.
AB  - Despite medical and surgical advancements for the treatment of cardiovascular
      disease, mortality and morbidity remain high. Therapeutic angiogenesis has been
      one approach to address the major clinical need for a more effective treatment to
      restoring blood flow in ischemic organs and tissues, but current progress in
      angiogenic drug delivery is inadequate at providing sufficient bioavailability
      without causing safety concerns. An injectable sulfonated reversible thermal gel
      composed of a polyurea conjugated with poly(N-isopropylacrylamide) and sulfonate
      groups has been developed for the delivery of angiogenic factors. The thermal gel
      allowed for the spatiotemporal control of vascular endothelial growth factor
      release with a decreased initial burst release and reduced release rate in vitro.
      A subcutaneous injection mouse model was used to evaluate efficacious
      vascularization and assess the inflammatory response due to a foreign body.
      Thermal gel injections showed substantial vascularization properties by inducing
      vessel formation, recruitment and differentiation of vascular endothelial cells,
      and vessel stabilization by perivascular cells, while infiltrating macrophages
      due to the thermal gel injections decreased over time. These results demonstrated
      effective localization and delivery of angiogenic factors for therapeutic
      angiogenesis. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:
      3053-3064, 2018.

PMID- 30295998
TI  - Brain-selective mild hypothermia promotes long-term white matter integrity after
      ischemic stroke in mice.
AB  - INTRODUCTION: The neuroprotective effects of hypothermia in acute ischemic stroke
      are well documented. However, the mechanisms involved in the effects remain to be
      clearly elucidated and the role of hypothermia on long-term white matter
      integrity after acute ischemic stroke has yet to be investigated. AIMS: To
      investigate the role of mild focal hypothermia on long-term white matter (WM)
      integrity after transient cerebral ischemia. RESULTS: Mild focal hypothermia
      treatment immediately after ischemic stroke significantly promotes WM integrity
      28 days after the occlusion of the middle cerebral artery (MCAO) in mice. Higher
      integrity of white matter, lower activation of total microglia, less infarct
      volume, and better neurobehavioral function were detected in hypothermia-treated
      mice compared to normothermia-treated mice. Furthermore, we found that
      hypothermia could decrease detrimental M1 phenotype microglia and promote healthy
      M2 phenotype microglia. In vitro, results also indicated that hypothermia
      promoted oligodendrocytes differentiation and maturation after oxygen glucose
      deprivation. CONCLUSION: Hypothermia promotes long-term WM integrity and inhibits
      neuroinflammation in a mouse model of ischemic brain injury.

PMID- 30295999
TI  - Developing evidence-based and accountable health policy in heart failure.

PMID- 30296000
TI  - Long-term retention of avulsed maxillary permanent incisors replanted after
      prolonged non-physiological storage.
AB  - Ankylosis and external replacement resorption (ERR) are two typical biological
      responses to delayed replantation of avulsed teeth in cases where adequate root
      canal treatment is performed. The patient's growth stage affects the progression
      of root resorption and the long-term outcome of the affected teeth. This case
      report describes the long-term outcome of an 18.5-year-old patient following an
      accident in which both of his maxillary central incisors were avulsed and
      replanted after four hours of non-physiological storage. ERR and ankylosis of
      teeth 11 and 21 were detected clinically and radiographically during the second
      year of follow-up. Sixteen years after replantation, replacement resorption was
      progressing very slowly, enabling functional tooth retention with favorable
      esthetics. Young adults, with delayed replantation of avulsed teeth, may benefit
      from tooth retention with slow ERR.

PMID- 30296002
TI  - The extracellular protease AdamTS-B inhibits vein formation in the Drosophila
      wing.
AB  - Vein patterning in the Drosophila wing provides a powerful tool to study
      regulation of various signaling pathways. Here we show that the ADAMTS
      extracellular protease AdamTS-B (CG4096) is expressed in the embryonic wing
      imaginal disc precursor cells and the wing imaginal disc, and functions to
      inhibit wing vein formation. Knock-down of AdamTS-B displayed posterior
      crossveins (PCVs) with either extra branches or deltas, or wider PCVs, and a
      wandering distal tip of the L5 longitudinal vein. Conversely, over-expression of
      AdamTS-B resulted in a complete absence of the PCV, an incomplete anterior
      crossvein, and missing distal end of the L5 longitudinal vein. We conclude that
      AdamTS-B inhibits wing vein formation through negative regulation of signaling
      pathways, possibly BMP as well as Egfr, displaying the complexity of roles for
      this family of extracellular proteases.

PMID- 30296001
TI  - Towards patterned bioelectronics: facilitated immobilization of exoelectrogenic
      Escherichia coli with heterologous pili.
AB  - Biosensors detect signals using biological sensing components such as redox
      enzymes and biological cells. Although cellular versatility can be beneficial for
      different applications, limited stability and efficiency in signal transduction
      at electrode surfaces represent a challenge. Recent studies have shown that the
      Mtr electron conduit from Shewanella oneidensis MR-1 can be produced in
      Escherichia coli to generate an exoelectrogenic model system with well
      characterized genetic tools. However, means to specifically immobilize this
      organism at solid substrates as electroactive biofilms have not been tested
      previously. Here, we show that mannose-binding Fim pili can be produced in
      exoelectrogenic E. coli and can be used to selectively attach cells to a mannose
      coated material. Importantly, cells expressing fim genes retained current
      production by the heterologous Mtr electron conduit. Our results demonstrate the
      versatility of the exoelectrogenic E. coli system and motivate future work that
      aims to produce patterned biofilms for bioelectronic devices that can respond to
      various biochemical signals.

PMID- 30296003
TI  - Log margin-to-thickness ratio improves disease-specific survival prediction in
      oral cancer: A single cancer centre database.
AB  - OBJECTIVE: We examined whether dynamic margin criteria margin-to-thickness (MTR)
      ratio has superior predictive value compared with the resection margin or tumour
      thickness alone in the survival outcome in oral squamous cell carcinoma (OSCC).
      DESIGN: This is a retrospective cohort study. SETTING: Oral squamous cell
      carcinoma patients treated in Kaohsiung Veterans General Hospital Cancer Center
      between January 2006 and December 2013. PARTICIPANTS: A cohort of 302 patients
      with OSCC who had undergone surgical management. MAIN OUTCOMES MEASURES: Log MTR
      was calculated for each patient, and survival data were analysed using a
      multivariable Cox regression model. Discriminative analysis was performed using
      chi-square, Akaike information criterion (AIC) and Harrell's C tests. RESULTS:
      After assessing for discriminative ability, the linear trend of log MTR surpassed
      those of resection margin and tumour thickness in chi-square, AIC and Harrell's C
      tests for the advanced pathologic T (pT) category. A multivariate Cox
      proportional hazard regression model revealed that log MTR <33% was associated
      with less favourable 5-year disease-specific survival (DSS) (P = 0.006) in the
      entire oral cancer study cohort. Other significant factors included perineural
      invasion (P = 0.021), pT category, (P = 0.005), pathologic N category (P < 0.001)
      and differentiation category (P = 0.022). CONCLUSIONS: Log MTR < 33% may be a
      predictor of less favourable outcome in the DSS of OSCC. Log MTR outperformed
      both resection margin and tumour thickness alone in terms of discriminative
      analysis. Our study could help in presurgical planning for high-risk patients and
      in aiding the decision-making process for adjuvant treatment.

PMID- 30296004
TI  - Emergency Preparedness Training for Hospital Nursing Staff, New York City, 2012
      2016.
AB  - PURPOSE: Many nurses are trained inadequately in emergency preparedness (EP),
      preventing them from effectively executing response roles during disasters, such
      as chemical, biological, radiological, nuclear, and explosive (CBRNE) events.
      Nurses also indicate lacking confidence in their abilities to perform EP
      activities. The purpose of this article is to describe the phased development of,
      and delivery strategies for, a CBRNE curriculum to enhance EP among nursing
      professionals. The New York City (NYC) Department of Health and Mental Hygiene
      (DOHMH) and the National Center for Disaster Preparedness at Columbia
      University's Earth Institute led the initiative. METHODS: Curriculum development
      included four phases. In Phases I and II, nursing staff at 20 participating NYC
      hospitals conducted 7,177 surveys and participated in 20 focus groups to identify
      training gaps in EP. In Phase III, investigators developed and later refined the
      CBRNE curriculum based on gaps identified. In Phase IV, 22 nurse educators
      (representing 7 of the original 20 participating hospitals) completed train-the
      trainer sessions. Of these nurse educators, three were evaluated on their ability
      to train other nurses using the curriculum, which investigators finalized.
      FINDINGS: The CBRNE curriculum included six modules, a just-in-time training, and
      an online annual refresher course that addressed EP gaps identified in surveys
      and focus groups. Among the 11 nurses who were trained by three nurse educators
      during a pilot training, participant knowledge of CBRNE events and response roles
      increased from an average of 54% (range 45%-75%) on the pre-test to 89% (range
      80%-90%) on the posttest. CONCLUSIONS: By participating in nursing CBRNE
      training, nurses increased their knowledge of and preparedness to respond to
      disasters. The train-the-trainer curriculum is easily adaptable to meet the needs
      of other healthcare settings. CLINICAL RELEVANCE: The CBRNE curriculum can be
      used to train nurses to better prepare for and more effectively respond to
      disasters.

PMID- 30296005
TI  - Choosing a dialyzer: What clinicians need to know.
AB  - The objectives of hemodialysis have moved from the diffusive clearance of small
      molecular weight uremic toxins and achieving dialyzer urea adequacy targets to
      emphasis on improving clinical outcomes in end stage renal failure patients by
      increasing larger sized uremic toxin clearance. Clinical emphasis in the last few
      decades has focused on increasing middle molecule weight toxin clearance by
      hemodiafiltration. Although long-term data is still lacking, short-term outcomes
      appear promising. Advancements in nanotechnology have now introduction a new
      generation of medium cut-off membrane dialyzers which allow diffusive clearance
      of similar middle molecular weight uremia toxin clearance as hemodiafiltration,
      without increased albumin losses. As these dialyzers have only recently been
      introduced into clinical practice, no long-term outcomes are available to
      determine the relative benefits or advantages of this approach. As dialyzers are
      now designed to maximize diffusive or convective clearance, or provide a
      combination, then clinicians can now choose dialyzers tailored to the individual
      patient needs depending on clinical circumstances. We review the key important
      features in choosing a dialyzer for patients with end stage renal failure and
      acute kidney injury.

PMID- 30296006
TI  - SIRT3 activator honokiol ameliorates surgery/anesthesia-induced cognitive decline
      in mice through anti-oxidative stress and anti-inflammatory in hippocampus.
AB  - AIMS: Increasing evidence indicates that neuroinflammatory and oxidative stress
      play two pivotal roles in cognitive impairment after surgery. Honokiol (HNK), as
      an activator of Sirtuin3 (SIRT3), has potential multiple biological functions.
      The aim of these experiments is to evaluate the effects of HNK on
      surgery/anesthesia-induced cognitive decline in mice. METHODS: Adult C57BL/6 mice
      received a laparotomy under sevoflurane anesthesia and HNK or SIRT3 inhibitor (3
      TYP) treatment. Cognitive function and locomotor activity of mice were evaluated
      using fear conditioning test and open field test on postoperative 1 and 3 days.
      Neuronal apoptosis in CA1 and CA3 area of hippocampus was examined using TUNEL
      assay. And Western blot was applied to measure the expression of pro-inflammatory
      cytokines and SIRT3/SOD2 signaling-associated proteins in hippocampus. Meanwhile,
      SIRT3 positive cells were calculated by immunohistochemistry. The mitochondrial
      membrane potential, malondialdehyde (MDA), and mitochondrial radical oxygen
      species (mtROS) were detected using standard methods. RESULTS: Honokiol
      attenuated surgery-induced memory loss and neuronal apoptosis, decreased
      neuroinflammatory response, and ameliorated oxidative damage in hippocampus.
      Notably, surgery/anesthesia induced an obviously decrease in hippocampal SIRT3
      expression, whereas the HNK increased SIRT3 expression and thus decreased the
      acetylation of superoxide dismutase 2 (SOD2). However, 3-TYP treatment inhibited
      the HNK's rescuing effects. CONCLUSIONS: These results suggested that activation
      of SIRT3 by honokiol may attenuate surgery/anesthesia-induced cognitive
      impairment in mice through regulation of oxidative stress and neuroinflammatory
      in hippocampus.

PMID- 30296007
TI  - Technique for tailoring complex demarcation in lung segmentectomy.
AB  - Segmentectomy is a widely adopted surgical procedure, however, experiences of
      tailoring the intersegmental border have rarely been reported. This paper
      investigates the strategy and results of tailoring complex demarcation during
      lung segmentectomy surgery. Because intersegmental demarcation can be divided
      into plane or curved types according to the location and stereo shape of a
      segment, a one-size-fits-all method for tailoring the intersegmental demarcation
      is obviously unreasonable. For tailoring a complex segmentectomy with two or more
      curved borders, tips including good exposure of the intersegmental demarcation,
      sharp-blunt combined dissection skill, "work-plane" extension, and "gate" opening
      techniques all contribute to an accurate segmentectomy. This technique, based on
      anatomical characteristics, can provide a cutting surface with a greater
      physiological shape and less curling of the edge, and should be recommended as a
      general standard method for tailoring complex demarcation.

PMID- 30296008
TI  - Comparative metagenomics of the gut microbiota in wild greylag geese (Anser
      anser) and ruddy shelducks (Tadorna ferruginea).
AB  - Gut microbiome contributes to host health by maintaining homeostasis, increasing
      digestive efficiency, and facilitating the development of immune system. Wild
      greylag geese (Anser anser) and ruddy shelducks (Tadorna ferruginea), migrating
      along the central Asian flyway, appear to be one of the most popular species in
      the rare birds rearing industries of China. However, the structure and function
      of the gut microbial communities associated with these two bird species remain
      poorly understood. Here, for the first time, we compared gut metagenomes from
      greylag geese to ruddy shelducks and investigated the similarities and
      differences between these two bird species in detail. Taxonomic classifications
      revealed the top three bacterial phyla, Firmicutes, Proteobacteria, and
      Fusobacteria, in both greylag geese and ruddy shelducks. Furthermore, between the
      two species, 12 bacterial genera were found to be more abundant in ruddy
      shelducks and 41 genera were significantly higher in greylag geese. A total of
      613 genera (approximately 70%) were found to be present in both groups. Metabolic
      categories related to carbohydrate metabolism, metabolism of cofactors and
      vitamins, lipid metabolism, amino acid metabolism, and glycan biosynthesis and
      metabolism were significantly more abundant in ruddy shelducks, while greylag
      geese were enriched in nucleotide metabolism and energy metabolism. The
      herbivorous greylag geese gut microbiota harbored more carbohydrate-active
      enzymes than omnivorous ruddy shelducks. In our study, a range of antibiotic
      resistance categories were also identified in the gut microbiota of greylag geese
      and ruddy shelducks. In addition to providing a better understanding of the
      composition and function of wild birds gut microbiome, this comparative study
      provides reference values of the artificial domestication of these birds.

PMID- 30296009
TI  - The relationships between urinary glycosaminoglycan levels and phenotypes of
      mucopolysaccharidoses.
AB  - BACKGROUND: The aim of this study was to use the liquid chromatography/tandem
      mass spectrometry (LC-MS/MS) method to quantitate levels of three urinary
      glycosaminoglycans (GAGs; dermatan sulfate [DS], heparan sulfate [HS], and
      keratan sulfate [KS]) to help make a correct diagnosis of mucopolysaccharidosis
      (MPS). METHODS: We analyzed the relationships between phenotypes and levels of
      urinary GAGs of 79 patients with different types of MPS. RESULTS: The patients
      with mental retardation (n = 21) had significantly higher levels of HS than those
      without mental retardation (n = 58; 328.8 vs. 3.2 MUg/ml, p < 0.001). The DS
      levels in the patients with hernia, hepatosplenomegaly, claw hands, coarse face,
      valvular heart disease, and joint stiffness were higher than those without.
      Twenty patients received enzyme replacement therapy (ERT) for 1-12.3 years. After
      ERT, the KS level decreased by 90% in the patients with MPS IVA compared to a 31%
      decrease in the change of dimethylmethylene blue (DMB) ratio. The DS level
      decreased by 79% after ERT in the patients with MPS VI compared to a 66% decrease
      in the change of DMB ratio. CONCLUSIONS: The measurement of GAG fractionation
      biomarkers using the LC-MS/MS method is a more sensitive and reliable tool than
      the DMB ratio for MPS high-risk screening, diagnosis, subclass identification,
      and monitoring the efficacy of ERT.

PMID- 30296010
TI  - Long-term follow-up of ICSI-conceived offspring compared with spontaneously
      conceived offspring: a systematic review of health outcomes beyond the neonatal
      period.
AB  - BACKGROUND: A significant increase in the use of intracytoplasmic sperm injection
      (ICSI) since its introduction in 1992 has been observed worldwide, including
      beyond its original intended use for severe male factor infertility. Concerns
      regarding ICSI include the effects of poor quality spermatozoa on offspring
      health and future fertility, and of the technique itself. The health and
      development of ICSI-conceived children beyond early infancy have not been
      comprehensively assessed. OBJECTIVE: A systematic review of health outcomes of
      ICSI-conceived offspring beyond the neonatal period compared to spontaneously
      conceived (SC) offspring. DESIGN: PubMed, OVID Medline/Embase, InformIT, Web of
      Science, and ProQuest databases were searched for studies reporting on health
      outcomes in ICSI-conceived offspring beyond 28 days after birth. MAIN OUTCOMES
      MEASURE(S): Physical and psychosocial health. RESULTS: The search strategy
      yielded 2826 articles. Of these, 2580 were not relevant or did not meet inclusion
      criteria and 138 were duplicates. One hundred and eight full-text papers were
      evaluated further, and 48 satisfied the inclusion criteria. Most studies reported
      on neurodevelopment during early infancy and childhood with reassuring results.
      Growth, vision, and hearing of ICSI and SC offspring also appear comparable,
      although important differences in general physical health, and particularly
      metabolic and reproductive health have been described, including recently poorer
      semen quality among ICSI-conceived young adult men compared to SC peers.
      CONCLUSION: Whilst neurodevelopment, growth, vision, and hearing appear similar
      between ICSI and SC children, evidence suggests differences in general physical
      health, and metabolic and reproductive endpoints. The clinical significance of
      many findings, however, remains unclear, and further prospective, large, and good
      quality studies with a focus on all these health outcomes in ICSI-conceived young
      adults are required.

PMID- 30296011
TI  - Highlights of eosinophilic chronic rhinosinusitis with nasal polyps in
      definition, prognosis, and advancement.
AB  - BACKGROUND: Tissue eosinophils are characteristic of inflammation in most but not
      all patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and may be
      useful for defining subgroups and making treatment choices. However, no
      consistent diagnostic criteria for CRSwNP with eosinophilic inflammation have
      been established. METHODS: Related literature review was performed and current
      developments in the diagnosis of eosinophilic CRSwNP were summarized. Details in
      histopathology, definition of tissue eosinophilia, eosinophil as an indicator of
      disease recurrence, eosinophilic shift, and related biomarkers in CRSwNP are
      included in this review article. RESULTS: Mucosal eosinophilia exhibits
      significant geographic and ethnic differences and may increase over time. Tissue
      eosinophilia can be defined using a cutoff value based on reference values from
      healthy mucosa, but typical disease-specific values should also be employed to
      increase sensitivity and specificity for clinical use. Recent developments
      highlight the diagnostic criteria for eosinophilic CRSwNP based on cluster
      analysis, which were also associated with clinical outcomes. Additionally, some
      promising eosinophil-relevant biomarkers, such as eosinophilic cation protein and
      interleukin 5 (IL-5), may be clinically applied as diagnostic or predictive tools
      for CRSwNP in the future. CONCLUSION: Sinonasal tissue eosinophilia is present in
      a majority of CRSwNP patients but is currently more common in the West than in
      the East. Cutoff values of eosinophils as the diagnostic criteria of eosinophilic
      CRSwNP are subject to change with geographic and ethnic differences over time. It
      will be important to identify validated eosinophil-related biomarkers in
      different continents/countries for future research and for the introduction of
      precision medicine.

PMID- 30296012
TI  - USP14 as a novel prognostic marker promotes cisplatin resistance via Akt/ERK
      signaling pathways in gastric cancer.
AB  - Gastric cancer (GC) ranks the third leading cause of global cancer mortality.
      Despite recent progress in surgery combined with chemotherapy, the outcomes of GC
      patients have barely improved. Therefore, better understanding of the molecular
      mechanisms involved in chemoresistance of GC may help develop novel strategies to
      treat this deadly disease. Previous evidence has shown aberrant expressions of
      USP14 in multiple malignancies, suggesting an important role of USP14 in
      tumorigenesis. However, its role in modulating chemoresistance in GC still
      remains elusive. In this study, we observed that USP14 levels were significantly
      increased in GC tissues compared to the paired normal tissues. Multivariate
      analysis demonstrated that USP14 level was an independent prognostic factor for
      DFS in GC patients. Silencing of USP14 promoted proteasomal degradation of p-ERK
      (T202/Y204) and p-Akt (T308/S473), thus inactivating Akt and ERK signaling
      pathways. Interestingly, silencing of USP14 alone was not sufficient to cause
      overt effects on cell growth, proliferation, and apoptosis, while resulting in
      significant apoptosis in the presence of cisplatin in GC cells. Thus, knockdown
      of USP14 sensitized GC cells to cisplatin by triggering cisplatin-induced
      apoptosis via impeding Akt and ERK signaling pathways. These results revealed a
      novel role of USP14 in modulating chemosensitivity of GC cells, suggesting USP14
      may serve as not only a prognostic marker, but also a potential therapeutic
      target for GC patients.

PMID- 30296013
TI  - Validation of CPS+EG, Neo-Bioscore, and modified Neo-Bioscore staging systems
      after preoperative systemic therapy of breast cancer: Protocol of a retrospective
      multicenter cohort study in China.
AB  - Prognostic assessment after preoperative systemic therapy (PST) is critical to
      develop a therapeutic strategy for breast cancer management. Currently, a
      clinical-pathologic staging system that incorporates ER status and nuclear
      grading (CPS + EG), and the Neo-Bioscore system that includes HER2 status into
      CPS + EG, are used to predict outcomes in patients with breast cancer after PST.
      While HER2-positive is recognized as a favorable factor in the Neo-Bioscore
      system based on results in patients administered one year of trastuzumab as anti
      HER2 therapy, most HER2-positive cases have difficulty accessing anti-HER2
      treatment in China. Therefore, it is crucial that a modified Neo-Bioscore staging
      system is developed that incorporates an additional factor of poor prognosis,
      HER2-positive status without trastuzumab treatment, to determine accurate
      prognosis. We propose a retrospective multicenter cohort study in China to
      validate CPS + EG, Neo-Bioscore, and the modified Neo-Bioscore system and
      determine the accuracy of prediction. Primary breast cancer patients without
      metastasis treated with PST and surgery in academic institutions or hospitals of
      provincial level in China will be included. Disease-free, disease specific, and
      overall survival will be calculated using the Kaplan-Meier Method, stratified by
      CPS + EG, Neo-Bioscore, and the modified Neo-Bioscore staging system. Areas under
      the curve of each staging system will be calculated. Multivariate analysis using
      Wald testing and maximum likelihood estimates in a Cox proportional hazards model
      will be conducted.

PMID- 30296014
TI  - Infection by Histoplasma capsulatum, Cryptococcus spp. and Paracoccidioides
      brasiliensis in bats collected in urban areas.
AB  - Epidemiological studies on endemic mycosis can be improved using molecular
      biology techniques to elucidate the role of bats as reservoirs and vectors of
      pathogenic fungi for infection of other animals and humans. The objective of this
      study was to explore the presence of Histoplasma capsulatum, Cryptococcus spp.
      and Paracoccidioides brasiliensis in insectivorous, frugivorous and nectarivorous
      bats collected in urban areas. We analysed 172 bats collected by the
      Epidemiological Surveillance Agency in 12 municipalities of the Midwest region of
      the state of Sao Paulo, Brazil. Spleen, liver, intestine and lung samples were
      subjected to microbiological culture and nested PCR analyses. Prevalence of H.
      capsulatum infection was 8.1% (14/172), with one bat found to be positive by
      fungal culturing, 12 positive by nested PCR and one positive by both methods. Two
      insectivorous bats were found positive by nested PCR for Cryptococcus spp., one
      in the spleen and the other in the spleen and lung. Two insectivorous bats showed
      natural infection by P. brasiliensis, in the spleen of one bat and the spleen and
      liver of the other. Our results reinforce the importance of bats as fungal
      dispersers in urban environments and the importance of constant epidemiologic
      surveillance because these synanthropic animals are in close contact with humans
      and animals.

PMID- 30296015
TI  - In situ and Operando Tracking of Microstructure and Volume Evolution of Silicon
      Electrodes by using Synchrotron X-ray Imaging.
AB  - The internal microstructure of a silicon electrode in a lithium ion battery was
      visualized by operando synchrotron X-ray radioscopy during battery cycling. The
      silicon particles were found to change their sizes upon lithiation and
      delithiation and the changes could be quantified. It was found that volume change
      of a particle is related to its initial size and is also largely determined by
      the changing surrounding electron-conductive network and internal interface
      chemical environment (e.g., electrolyte migration, solid-electrolyte interphase
      propagation) within fractured particles. Moreover, an expansion prolongation
      phenomenon was discovered whereby some particles continue expanding even after
      switching the battery current direction and shrinkage would be expected, which is
      explained by assuming different expansion characteristics of particle cores and
      outer regions. The study provides new basic insights into processes inside Si
      particles during lithiation and delithiation and also demonstrates the unique
      possibilities of operando synchrotron X-ray imaging for studying degradation
      mechanisms in battery materials.

PMID- 30296016
TI  - Toxins targeting transfer RNAs: Translation inhibition by bacterial toxin
      antitoxin systems.
AB  - Prokaryotic toxin-antitoxin (TA) systems are composed of a protein toxin and its
      cognate antitoxin. These systems are abundant in bacteria and archaea and play an
      important role in growth regulation. During favorable growth conditions, the
      antitoxin neutralizes the toxin's activity. However, during conditions of stress
      or starvation, the antitoxin is inactivated, freeing the toxin to inhibit growth
      and resulting in dormancy. One mechanism of growth inhibition used by several TA
      systems results from targeting transfer RNAs (tRNAs), either through preventing
      aminoacylation, acetylating the primary amino group, or endonucleolytic cleavage.
      All of these mechanisms inhibit translation and result in growth arrest. Many of
      these toxins only act on a specific tRNA or a specific subset of tRNAs; however,
      more work is necessary to understand the specificity determinants of these
      toxins. For the toxins whose specificity has been characterized, both sequence
      and structural components of the tRNA appear important for recognition by the
      toxin. Questions also remain regarding the mechanisms used by dormant bacteria to
      resume growth after toxin induction. Rescue of stalled ribosomes by transfer
      messenger RNAs, removal of acetylated amino groups from tRNAs, or ligation of
      cleaved RNA fragments have all been implicated as mechanisms for reversing toxin
      induced dormancy. However, the mechanisms of resuming growth after induction of
      the majority of tRNA targeting toxins are not yet understood. This article is
      categorized under: Translation > Translation Regulation RNA in Disease and
      Development > RNA in Disease RNA Interactions with Proteins and Other Molecules >
      Protein-RNA Recognition.

PMID- 30296017
TI  - Sustained and Bioresponsive Two-Stage Delivery of Therapeutic miRNA via Polyplex
      Micelle-Loaded Injectable Hydrogels for Inhibition of Intervertebral Disc
      Fibrosis.
AB  - Intervertebral disc degeneration (IDD) is frequently caused by gradual
      pathological changes inside intervertebral discs (IVDs) and progressive fibrosis.
      MicroRNA-29 (miR-29) family possesses potent fibrosis suppression capability, but
      their application for treatment of chronic IDD is limited due to lack of suitable
      local delivery systems. In this report, given various overexpressed matrix
      metalloproteinases (MMPs) during IDD, injectable MMP-degradable hydrogels
      encapsulating MMP-responsive polyplex micelles are developed for sustained and
      bioresponsive delivery of miR-29a into nucleus pulposus cells via a two-stage
      process. Cationic block copolymers are designed to complex miR-29a, and
      subsequently mixed with the poly(ethylene glycol) (PEG) gelation precursors and
      MMP-cleavable peptide cross-linkers for in situ formation of polyplex micelle
      encapsulated hydrogels in the diseased IVDs. In the presence of MMPs, the
      polyplex micelles are first released by MMP cleavage of the hydrogels, and
      subsequently, MMPs-responsive detachment of PEG shells from polyplex micelles
      contributes to efficient cellular uptake and endosomal escape. MiR-29a is
      demonstrated to effectively silence the expression of MMP-2, inhibit the fibrosis
      process, and reverse IDD in animal models through blocking the beta-catenin
      translocation pathway from the cytoplasm to the nucleus. This two-stage
      bioresponsive local miRNA delivery system represents a novel and promising
      strategy for the treatment of chronic IDD.

PMID- 30296018
TI  - Inadequate Accessibility: Why Uber Should Be a Public Accommodation Under the
      Americans With Disabilities Act.
AB  - This Comment will focus on Uber and its obligations under the Americans with
      Disabilities Act (ADA). While it may seem logical that Uber should adhere to the
      same ADA regulations as taxis, the relevant ADA provision only applies to private
      entities that are primarily engaged in the business of transporting people. To
      avoid these regulations, Uber asserts that it is primarily a technology company,
      rather than primarily a transportation company. However, the more expansive
      approach, consistent with the ADA's purpose of eliminating discrimination against
      persons with disabilities, is to classify Uber's services as public
      accommodations. While the ADA's public accommodation provision governs physical
      spaces such as restaurants, shopping centers, and offices, some jurisdictions
      have recently decided that web-based entities and services are public
      accommodations. Thus, even if a court were to accept Uber's claim that it is
      primarily a technology company rather than a transportation company, Uber would
      still be required to adhere to the ADA's public accommodation provision. This
      Comment presents and analyzes three rationales for defining Uber as a public
      accommodation under the ADA: (1) web-based activities are distinct public
      accommodations, (2) the physical vehicles that Uber operates are places of public
      accommodation, and (3) Uber is a "travel service" or "other service
      establishment" as defined in the ADA.

PMID- 30296019
TI  - Asbestos Trust Transparency.

PMID- 30296020
TI  - [Advantages of transesophageal three-dimensional echocardiography as a support in
      the atrial septal defect closure.]

PMID- 30296021
TI  - [Inappropriate response against Hepatitis B vaccine in health personnel of the
      National Hospital, Paraguay.]
AB  - Introduction: health personnel are a risk group for acquiring hepatitis B. The
      vaccine against it is effective but requires evaluation of the immune response
      with the dosage of anti-HBs. Objective: Objectives: to determine the
      immunological response to the vaccine against hepatitis B in physicians, nurses
      and medical students of the National Hospital, Paraguay. Methods: an
      observational, analytical and cross-sectional study was conducted in a sample of
      120 health workers during 2017. The level of anti-HBs was determined with
      quantitative immunoassay and demographic and clinical variables were recorded,
      with prior informed consent. Results: the sample was integrated with 79 women and
      41 men. The mean age was 28+/-7 years. Physicians (62.5%), nurses (20%) and
      medical students (17.5%) were included. The mean BMI was 24.7 +/- 3.8 kg/m2.
      Adequate serum levels of anti-HBs (> 100 IU / mL) were detected in 64% of the
      health personnel. Obesity was a factor associated with poor response to the
      vaccine (p 0.02). Sex, age, the time elapsed since the last dose and smoking were
      factors not significantly associated with the lack of response to the vaccine.
      Conclusion: inadequate response to HB vaccine was found in 36%. Obesity was
      significantly associated with poor immunological response.

PMID- 30296022
TI  - [Characteristics of bloodstream infections in adult patients of two third level
      centers of Cordoba, Argentina.]
AB  - Background: Bloodstream infections (BI) are associated with high morbidity and
      mortality. Objective: To determine epidemiological, microbiological and clinical
      features of community (CA-BI) and nosocomial bloodstream infections (N-BI).
      Methods: Bacteremia and fungemia events were retrospectively analyzed in two
      third-level hospitals between April 2009 and August 2013. Results: We identified
      1150 events of bloodstream infections, 53.2% were CA-BI. Gram negative
      microorganisms were isolated in 61%. The most frequent pathogens were Escherichia
      coli in CA-BI and Klebsiella pneumoniae in N-BI. Staphylococcus aureus was the
      most frequent gram positive organism. The main comorbidities were renal disease
      (39%) and malignancy (38%). There were 26.8% of primary bloodstream infections,
      and the main infection foci included respiratory (17.04%) and urinary tract
      (16.86%). A high percentage of gram-negative bacteria of CA-BI and N-BI were
      resistance to ampicillin sulbactam (40.2% and 57.5%), cephalothin (36.7% and
      46.8%), trimethoprim-sulfamethoxazole 32.8% vs 35.5%) and ciprofloxacin (24.6%
      and 35.3%). Methicillin-resistant Staphylococcus aureus were more frequently into
      ITS-IH (31.4% vs 11.8%, p = 0.007). Conclusions: Clinical and epidemiological
      characteristics of CA-BI and N-BI were similar to those reported by other Latin
      American studies. We observed some differences in antimicrobial resistance
      profiles. We emphasize the importance of local epidemiological surveillance to
      choose appropriate empirical treatments. Conclusions: Clinical and
      epidemiological characteristics of CA-BI and N-BI were similar to those reported
      by other Latin-American studies. We observed some differences in antimicrobial
      resistance profiles. We emphasize the importance of local epidemiological
      surveillance to choose appropriate empirical treatments.

PMID- 30296023
TI  - [Impact of an educational program related to basic knowledge of Chagas disease in
      a population of the Argentine Northeast.]
AB  - Introduction: In Avia Terai city, in Northeast of Argentina, a local program of
      Prevention and Control of Chagas disease was developed, guided by the principles
      of Primary Health Care. The objective of this study was to evaluate the change in
      knowledge regarding Chagas disease after the implementation of the strategy of
      Information, Education and Social Communication component of the local program in
      the urban area of Avia Terai in 2012. Methods: A cross-sectional design was used
      in two moments. A multistage sampling was carried out. The unit of analysis
      corresponded to heads of household of the selected house. A questionnaire adapted
      from Sanmartino and Crocco was used, which includes 3 dimensions and 15 basic
      knowledge referring to Chagas disease. Results. 609 residents were surveyed.
      Regarding the level of basic knowledge about Chagas disease, in level III an
      increase was observed in 2012 with respect to the previous year, from 56.6% to
      66.2% (p> 0.0001). While regarding the congenital transmission, a decrease in the
      proportion of correct responses was observed. Conclusion. After the
      implementation of a local program of information, education and social
      communication, an increase in basic knowledge about Chagas disease was observed.
      Results: 609 residents were surveyed. Regarding the level of basic knowledge
      about Chagas disease, in level III an increase was observed in 2012 with respect
      to the previous year, from 56.6% to 66.2% (p> 0.0001). While regarding the
      congenital transmission, a decrease in the proportion of correct responses was
      observed. Conclusion: After the implementation of a local program of information,
      education and social communication, an increase in basic knowledge about Chagas
      disease was observed.

PMID- 30296024
TI  - [Use of body segments for assess growth and nutritional status in children and
      adolescents.]
AB  - Introduction: Weight and height are essential information to assess growth and
      nutritional status in pediatrics. The determination of them by direct method is
      difficult in hospitalized patients. The objective was to analyze the correlation
      between weight and mid arm circumference (MAC), and between height and knee
      height (KH) of children and teenagers so it can be used to asses growth and
      nutritional status in hospitalized children. Population and methods: An
      observational, descriptive and cross-sectional study was carried out. We included
      children and teenagers of both gender of 2 and 19 years old. To establish the
      correlation, the correlation coefficient r and determination R2 were calculated
      with a significance of p <0.05, plotting the correlation. The MedCalc V12.5.0.0
      software was used to analyze the data. Results: Data from 861 subjects were
      collected. 484 females (56.2% CI95% 52.8-59.5), and 377 males (43.8% CI 95% 40.4
      47.2) aged between 2 and 19 years. A correlation was obtained between the KH and
      the height of r = 0.98 for both sexes, (R2 = 0.96 females and R2 = 0.97 in
      males), p <0.001. The MAC showed a correlation with the weight of r = 0.92 (R2 =
      0.76) in males and r = 0.87 (R2 = 0.85) in females, both with p <0.001.
      Conclusions: Body segments KH and MAC have a high correlation with height and
      weight, respectively. That is why we propose to use them for the assessment of
      growth and nutritional status in hospitalized children with functional
      limitations.

PMID- 30296025
TI  - [Prevalence of Chlamydia trachomatis in pregnant women during the first trimester
      in a private institution in Cordoba.]
AB  - Introduction: The presence of C. trachomatis in pregnant women can cause
      premature rupture of membranes, postpartum endometritis and preterm birth.
      Clinical diagnosis is more difficult among those who have an asymptomatic
      infection. Objective: know the prevalence of Chlamydia trachomatis in pregnant
      women in their first trimester and to detect if there are any factors associated
      with this bacterium. Material and methods: Prospective, descriptive, cross
      sectional and correlational study performed at Clinica Universitaria Reina
      Fabiola, in Cordoba, between October 2016 and April 2017. C. trachomatis was
      detected through the Real Time PCR technique in first void urine samples.
      Results: 350 pregnant women were studied. The global prevalence was of 2% with a
      13,3% in women under 25 years old (p< 0,001). A similar pattern was observed with
      respect to the educational level, with a higher prevalence on those who only had
      primary education, 18,2% (p<0.001); in women who presented a low gynecological
      sign or symptom 6,8% (p< 0,001) and in those patients whose sexual initiation was
      before 18 years old,  3,3% (p< 0,030). Conclusion: It is advisable to implement
      C. trachomatis screening as part of the pre natal screening in all pregnant women
      under 25 years old. Argentinian health care system should take this problem into
      account in order to achieve a rational control over the infections caused by this
      bacterium.

PMID- 30296026
TI  - Positive correlation between proteasome activity and polyphenols in the
      telencephalon of adult female mice.
AB  - INTRODUCTION: Proteasome regulates proteostasis, and can be compromised in
      neurodegenerative diseases. Thus, our aim was to correlate the activity of
      proteasome to the level of polyphenols in telencephalon during murine adulthood.
      METHODS: Proteasome activity, polyphenols and other variables (glucose and
      hydroperoxides) were analysed in Balb/c female telencephala (n = 20, age = 4-12
      months), using multivariate methods. RESULTS: The following values were found:
      proteasome activity = 3.1 +/- 0.6 FI/ug of tissue proteins, glucose = 0.1 +/- 0.0
      ug/ug, hydroperoxides = 363.4 +/- 96.6 OD/ug, and polyphenols = 0.1 +/- 0.0
      ng/ug. Polyphenols reduced during aging showed a direct correlation with
      proteasome (Pearson's coefficient = 0.43, p = 0.0590, and a multivariate linear
      regressive coefficient = 17.85, p = 0.0216), with glucose and hydroperoxides
      being not involved (p>0.1). This correlation was confirmed by partial least
      square regression (beta = 0.67). CONCLUSION: Proteasome activity can be affected
      during ageing, and promoted by telencephalic polyphenol levels. Thus, these diet
      compounds might exert benefits in adult brain.

PMID- 30296028
TI  - [Infrequent clinicopathological presentation of acute tubular damage by light
      Chains in multiple myeloma.]

PMID- 30296027
TI  - [Nutritional contribution the school canteens program to the children of ten
      municipal schools in the city of Cordoba, Argentina.]
AB  - Introduction: School canteens are one of the most widespread programs in recent
      decades which may have significant impacts on nutrition, health, growth and
      development in children. Objetive: To assess the nutritional contribution of
      School Canteens (PCE) program to children from municipal schools of Cordoba.
      Material and methods: Was a descriptive and analytical study. I applied an
      observation guide and ration weighing measurements of the school canteens food
      supply and food recall method was used 24 hours a sample of 170 school children.
      Results: The breakfasts/snacks they had a deficit in Calcium, vitamin A and C and
      iron and excess of simple sugars. The lunches they had a excess of saturated fats
      and deficit of energy, calcium, iron, fiber and vitamin A. The food consumption
      of school children was high in discretionary calories, sugars and saturated fats
      and deficit in fiber, calcium and vitamin A, associated with some
      sociodemographic characteristics.There had associations between the inadequacy of
      the target intake of calcium and vitamin found and suboptimal quality and dining
      in these nutrients (p< 0,05). Conclusions: We conclude what in this context there
      are nutritional aspects that are necessary improve.

PMID- 30296029
TI  - [Case report: intestinal pneumatosis]
AB  - Objective: To present a recent to increase understanding, diagnosis and treatment
      of intestinal pneumatosis clinical case, considering the distinctive
      characteristics of the disease and to expand knowledge about the management of
      this condition. Methods: The case of a female patient aged 65, originally from
      Bolivia, with a history of osteoarthritis, osteoporosis, asthma and allergies
      repetition occurs. The patient was admitted to the Department of Surgery No. 1
      HNC in November 2015, with an unclear clinical picture. During admission of air
      bubbles present in the colonic mucosa and tumor lesion is discovered duodenum.
      Quickly it begins with treatment and adequate support for stabilization. A
      literature search and an update of the latest updates regarding this disease
      arises. medical seekers popularity as PUBMED, UP TO DATE, VBS were used. a series
      of articles about it were selected.The patient cited in this work has given us
      the corresponding written consent for the anonymous publication with scientific
      purposes about her information.Also we declare the absence of external financing
      and conflicts of interest. Conclusions: it was concluded that management should
      generally be conservative, excluding the case of complications (obstruction,
      perforation) and suspected intestinal ischemia. Exploratory laparoscopy may be
      helpful to determine the appropriate behavior. Conservative treatment includes
      antibiotics, hyperbaric oxygen and supportive measures.

PMID- 30296030
TI  - AVR ST-segment elevation as predictor of three-vessel disease in non-ST-segment
      elevation acute coronary syndrome.
AB  - Electrocardiogram is a useful tool for the diagnosis of acute coronary syndrome.
      In recent years, ST-segment changes in aVR have been shown to provide valuable
      information about coronary anatomy and early risk stratification of this
      condition.

PMID- 30296031
TI  - [External fixation in reconstructive surgery: crossed leg flap.]
AB  - Introduction: Lower limb coverage defects are sometimes associated with
      disruption of vascular pedicles that make it impossible to perform free flaps. In
      these cases the crossed leg flap is a good therapeutic alternative. T Material
      and methods: wo patients presented a coverage defect non-treatable with 
      microvascularized free flap after being operated on multiple times in the lower
      limbs. A cross leg flap was performed stabilizing both lower limbs with an
      external fixator. Both patients showed a satisfactory recovery returning to walk
      without additional help. Conclusion: Crossed leg flap stabilized by external
      fixation is a valid alternative for soft tissue defects.

PMID- 30296032
TI  - [Patellar osteomyelitis. A diagnostic challenge.]
AB  - Osteomyelitis is a rare infection that is considered to be a children's disease.
      Diagnosis is frequently delayed because it is an uncommon pathology and is
      presented in various ways. After its diagnosis and treatment, the result is
      favourable in children. We present a clinical case that shows difficulties in its
      diagnosis. A high index of suspicion should be addressed for early recognition.

PMID- 30296033
TI  - [Azitromycin efficacy in Bronchial Asthma refractory to conventional therapy.]

PMID- 30296034
TI  - A Crispr Future for Gene-Editing Regulation: a Proposal for an Updated
      Biotechnology Regulatory System in an Era of Human Genomic Editing.
AB  - Recent developments in gene-editing technology have enabled scientists to
      manipulate the human genome in unprecedented ways. One technology in particular,
      Clustered Regularly Interspaced Short Pallindromic Repeat (CRISPR), has made gene
      editing more precise and cost-effective than ever before. Indeed, scientists have
      already shown that CRISPR can eliminate genes linked to life-threatening diseases
      from an individual's genetic makeup and, when used on human embryos, CRISPR has
      the potential to permanently eliminate hereditary diseases from the human genome
      in its entirety. These developments have brought great hope to individuals and
      their families, who suffer from genetically linked diseases. But there is a dark
      side: in the wrong hands, CRISPR could negatively impact the course of human
      evolution or be used to create biological weaponry. Despite these possible
      consequences, CRISPR remains largely unregulated due to the United States's
      outdated regulatory scheme for biotechnology. Moreover, human embryo research,
      which is likely critical to maximizing the therapeutic applications of CRISPR, is
      not easily undertaken by scientists due to a number of federal and state
      restrictions aimed at preventing such research. This Note examines the possible
      benefits and consequences of CRISPR and discusses the current regulations in both
      the fields of biotechnology and human embryo research that hamper the
      government's ability to effectively regulate this technology. Ultimately, this
      Note proposes a new regulatory scheme for biotechnology that focuses on the
      processes used to create products using CRISPR, rather than the products
      themselves, with a focus on enabling ethical research using human embryos to
      maximize the potential benefits of CRISPR.

PMID- 30296035
TI  - [UNRESOLVED PROBLEMS OF THE EVALUATION OF MYOCARDIAL BLOOD SUPPLY].
AB  - Over the past few decades, a steady rise in the incidence, morbidity and
      mortality from cardiovascular diseases has been observed throughout the world.
      The most common pathology is coronary heart disease (CHD) which, in addition, is
      responsible for chronic heart failure in more than one third of the cases.
      Patients with coronary heart disease are in need of early diagnosis and timely
      treatment. This article provides an overview of current scientific literature
      concerning anatomy of coronary vessels, their age-related changes, and modern
      radiological diagnostic methods of the lesions associated with coronary artery
      disease.

PMID- 30296036
TI  - Improving Early Learning: State Legislative Actions in 2018.
AB  - (1) Since 2002, annual state spending on preschool has increased from $2.4
      billion to $7.6 billion. (2) Nineteen percent of the nearly 20 million children
      under age 5 in the U.S. live in poverty. (3) Forty-eight percent of children from
      low-income families are ready for school at age 5, compared with 75 percent of
      children from families with moderate and high incomes.

PMID- 30296037
TI  - [CARDIOPROTRECTIVE EFFECT OF REMOTE POSTCONDITIONING: MECHANISMS AND
      POSSIBILITIES OF CLINICAL APPLICATION].
AB  - Experimental data indicate that postconditioning at a distance is an effective
      method for cardiac protection against reperfusion injury. Remote postconditioning
      prevents reperfusion necrosis and apoptosis of cardiomyocytes, decreases a
      probability of postinfarction remodeling of the heart. Cardioprotective effect of
      remote postconditioning depends on the release of tissue factor(s) increasing
      cardiac tolerance to long-term ischemia-reperfusion after transient ischemia.
      Clinical investigations show that postconditioning at a distance is an effective
      method for the prevention of reperfusion injury of the heart during coronary
      artery bypass surgery.

PMID- 30296038
TI  - Addressing Children's Mental Health.
AB  - (1) Untreated mental disorders and mental illness in children can lead to costly
      outcomes such as school dropout, substance use and suicide. (2) Half of lifetime
      cases of mental illness begin by age 14 and 75 percent of all lifetime cases
      present by age 24. (3) Early intervention and access to treatment may decrease
      the financial and health burdens associated with mental illness.

PMID- 30296039
TI  - [THE RELATIONSHIP BETWEEN SERUM AND LIQUOR IL-1beta, IL-6, TNFalpha, IL-10 LEVELS
      AND CLINICAL, COGNITIVE AND FUNCTIONAL CHARACTERISTICS IN ACUTE ISCHEMIC STROKE].
AB  - Introduction: Inflammation is probably the main process that links cardiovascular
      risk factors with damage to blood vessels and neurons. Elucidation of mechanisms
      of this relationship is an important issue. Materials and methods: 70 acute
      stroke patients were studied to assess their neuropsychological (MMSE, MoCA, FAB,
      Clock Drawing Test, Shulte Tables and Verbal Fluency) and functional status (mRS,
      Rivermead Mobility Index). The serum and liquor IL-1beta, IL-6, TNFa and IL-10
      levels were analyzed. Control group included subjects without cerebrovascular
      diseases. Results: Stroke patients had higher IL-10 serum concentration than
      controls. No difference was found for other cytokines. There was correlation
      between serum and liquor cytokines levels. We found positive correlation between
      IL-1beta, IL-6 and IL-10 levels. High IL-1beta concentration was associated with
      vascular risk factors, cardio embolic stroke, enhanced severity of cerebral
      stroke, low processing speed, impaired executive and visual-spatial functions and
      higher grade of mRS on discharge. The same pattern was revealed for IL-6 and IL
      10. IL-6 level was related to mRS without relation to NIHSS on admission. High
      TNFa concentration was linked with vascular risk factors, low MMSE score and
      processing speed. Discussion: Despite the antagonistic effects of IL-1beta, IL-6
      and IL-10 on inflammation, associations of these cytokines with anamnestic,
      clinical, neuropsychological and functional characteristics were similar in acute
      ischemic stroke. Probably, this fact indicates that during the acute ischemic
      brain damage process the immune response develops at the same time in pro- and
      anti-inflammatory directions. Its magnitude correlates with the damage severity
      and is associated with the effects of vascular risk factors before stroke.

PMID- 30296040
TI  - [ANTIBACTERIAL THERAPY AT DIFFERENT STAGES OF TREATMENT OF INFECTIOUS
      ENDOCARDITIS. DO WE ACT CORRECTLY]?
AB  - Objective: To study characteristics of antibacterial therapy (ABT) at different
      stages of treatment of patients with infective endocarditis (IE) in clinical
      practice. Materials and methods: In retrospective (2001 to 2008) and prospective
      (2008 to 2014) studies lasting 14-years, 302 hospitalized patients with confirmed
      native valve IE were given antibiotic therapy at outpatient and inpatient stages
      of treatment. The choice of antibacterial drugs, duration and side effects of
      prolonged use of antibiotics (AB) were analyzed in comparison with the results of
      hospital treatment of patients with IE. Results: It was shown that outpatients
      with IE due to fever without a specific diagnosis, were frequently prescribed
      short courses of antibiotics with the prevalence of ceftriaxone monotherapy and
      its combination with aminoglycosides as the starting treatment under hospital
      conditions. The cases of incompliance with the recommended duration of
      antimicrobial therapy were documented. The most common side effects of AB
      included diarrheal disorders, but the most serious problem was nephrotoxicity
      resulting in total or partial withdrawal of ABT. Conclusions: The potential of
      antibiotic treatment of IE is employed but incompletely, the main obstacles to
      the implementation of adequate antibiotic therapy of IE being the low rate of
      early diagnosis of the disease including etiological one and the unacceptable
      level of long-term safety of ABT for the patients.

PMID- 30296041
TI  - [REGRESSION OF ATHEROSCLECROTIC LESIONS: MEDICAMENTAL AND ALIMENTARY FACTORS].
AB  - The article reports results of clinical studies aimed to elucidate the influence
      of medicines on the size and density of atherosclerotic plaques in the walls of
      coronary and cerebral arteries. The phenomenon of regression of atherosclerotic
      lesions in the survivors of Leningrad siege during a long period of starvation is
      analyzed. The influence of inhibitors of angiotensin-converting enzyme on
      apoptosis of smooth muscle and foam cells of atherosclerotic plaques in the
      sanological mechanisms of atherosclerosis is discussed. The concept of natural
      regression of atherosclerosis is formulated and the necessity of development of
      the methods for is pharmacological activation are formulated.

PMID- 30296042
TI  - [CHARACTERISTIC OF APOPTOSIS OF CORONARY ARTERY CELLS WITH ATHEROSCLEROTIC
      LESIONS].
AB  - Aim: To study apoptosis of endothelial cells (EC), macrophages (MF) and smooth
      muscle cells (SMC) in the early atherosclerotic process (prior to plaque
      formation), elucidate mechanisms of its realization and evaluate effect on
      progression of atherosclerosis. Materials and methods: Histopathological studies
      were performed on coronary arteries affected by atherosclerosis taken at autopsy
      of patients with coronary heart disease (n = 63). To detect apoptosis, the TUNEL
      method was used for calculating the apoptotic index (AI) in paraffin sections.
      Phenotyping the cells and test for expression of active caspase 3 (AC-3) and
      apoptosis-inducing factor (AIF) were performed using sections of coronary
      arteries stained by immunohistochemistry. Results: The study of apoptosis showed
      a significant (p <0.0001) increase in AI of SMC, EC, MF coronary arteries
      affected by atherosclerosis compared with unaffected vessels. Progression of the
      atherosclerotic process led to a decrease of AI of SMC and EC. Statistical
      analysis revealed moderate feedback between AI of SMC and neointimal thickness in
      the development of atherosclerotic lesions (r = -0,44, p <0.0001). The amount of
      the AC-positive SMC and EC at the stage of lipoidosis significantly (p <0.0001)
      exceeded the number of AC -positive SMC at the liposclerosis stage. Expression of
      AIF was observed in the nuclei of EC in the newly formed vessels of hyperplastic
      intima. Conclusions: Early atherosclerotic lesions of the coronary arteries are
      accompanied by intense apoptosis of SMC, EC and MF. The intensity of apoptosis of
      SMC and EC decreases with the development of atherosclerosis. Progression of
      intimal hyperplasia at the early stages of atherosclerosis is associated with
      reduced apoptosis of smooth muscle cells and enhanced macrophage apoptosis.
      Apoptosis of SMC and MF is caspase-dependent. Apoptosis of endothelial cells can
      occur both with the participation of caspases and independently of them (with
      AIF).

PMID- 30296043
TI  - [CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND ANEMIA: CLINICAL MANIFESTATIONS AND
      THERAPEUTIC STRATEGY].
AB  - : Anemia refers to manifestations of systemic inflammation in chronic obstructive
      pulmonary disease (COPD) and a factor aggravating the disease. Objective: To
      study gender characteristics of anemia in patients with COPD, to increase the
      effectiveness of treatment through the use of pharmacological agents
      erythropoietin and enteral iron. Materials and methods: The paper presents
      clinical data on 74 patients with stage II/III COPD and anemia along with results
      of the treatment of 49 patients who received standard therapy in addition to
      epoetin and Sorbiferdurules. Results: Patients with COPD much more frequently
      presented with iron deficiency anemia (IDA): 63 patients (85.1%) dominated by
      women (39 or 61.9% ) with men accounting only for 24 or 38.1% of the total. 11
      patients (14.9%) had normochromic normocytic anemia with the parameters of anemia
      of chronic disease. The incidence of IDA in both groups correlated with age; it
      was largely a moderately severe condition that much more frequently occurred in
      women (24 out of 39 patients - 61,5%) than in men in whom the mild form of iron
      deficiency prevailed (14 of 24 patients - 58,3%). Conclusion: The overall
      prevalence of anemia concomitant with COPD was estimated at 26.5%. It was
      documented in44 women (33.7%), i.e. in each third patient. It occurred less
      frequently in men (30 or 20,7%). The presence of anemia deteriorates conditions
      of the patients, especially female ones, who more often suffer from shortness of
      breath, impaired general health status , fatigue, and depression; moreover, they
      more frequently need hospitalization. Correction of anemia with erythropoietin
      and iron preparations for the internal use can improve physical endurance of the
      patients, reduce cough intensity and shortness of breath, promote positive
      dynamics of physical tolerance for a prolonged period after the completion of
      antianemic therapy.

PMID- 30296044
TI  - [C-REACTIVE PROTEIN AS AN INDICATOR OF RISK OF CARDIOVASCULAR COMPLICATIONS IN
      PATIENTS WITH TYPE 2 DIABETES MELLITUS AND ITS CORRECTION].
AB  - The study included 74patients (22 men and 52 women) aged 48-75yr with type 2
      diabetes mellitus (DM2). 62 (88,6%) of them had grade II hypertensive disease
      (grade II-III by the WHO/ISH-2010 classification), 46 (67%) presented with II-
      III class functional stable angina of effort, 7 patients survived myocardial
      infarction, two ones underwent coronary artery stenting. Patients of the main
      group (n=50) received oral hypoglycemic agents in combination with 1-exenatide
      (mimetic of glucagon-like peptide) in the form of two daily subcutaneous
      injections of 5 mcg for 1 month and 10 mcg during the next 5 months. Control
      patients (n=20) were given standard hypoglycemic therapy. Analysis of highly
      sensitive CRP demonstrated its increase to 3 mg/l and more in 72.8% of the
      patients that was responsible for the high risk of cardiovascular disorders.
      22,8% of the patients had a CRP level 1,0-2,9 mg/l (moderate risk) and only in
      4,2% it was lower than 1 mg/l (low risk). Six months of exenatide therapy
      resulted in normalization of glycemia, glycated hemoglobin and significant
      decrease of CRP level which suggested the improvement of the functional state of
      vascular endothelium due to reduction of chronic inflammation objectively
      reflected in the highly sensitive CRP level.

PMID- 30296045
TI  - Origins and Implications of Interfacial Capacitance Enhancements in C60-Modified
      Graphene Supercapacitors.
AB  - Understanding and controlling the electrical response at a complex electrode
      electrolyte interface is key to the development of next-generation
      supercapacitors and other electrochemical devices. In this work, we apply a
      theoretical framework based on the effective screening medium and reference
      interaction site model to explore the role of electrical double-layer (EDL)
      formation and its interplay with quantum capacitance in graphene-based
      supercapacitors. In addition to pristine graphene, we investigate a novel C60
      modified graphene supercapacitor material, which promises higher charge-storage
      capacity. Beyond the expected enhancement in the quantum capacitance, we find
      that the introduction of C60 molecules significantly alters the EDL response.
      These changes in EDL are traced to the interplay between surface morphology and
      charge localization character and ultimately dominate the overall capacitive
      improvement in the hybrid system. Our study highlights a complex interplay among
      surface morphology, electronic structure, and interfacial capacitance, suggesting
      general improvement strategies for optimizing carbon-based supercapacitor
      materials.

PMID- 30296047
TI  - Conformational-Switch Based Strategy Triggered by [18] pi Heteroannulenes toward
      Reduction of Alpha Synuclein Oligomer Toxicity.
AB  - A water-soluble meso-carboxy aryl substituted [18] heteroannulene (porphyrin) and
      its Zn-complex have been found to be viable in targeting alpha-Syn aggregation at
      all its key microevents, namely, primary nucleation, fibril elongation, and
      secondary nucleation, by converting the highly heterogeneous and cytotoxic
      aggresome into a homogeneous population of minimally toxic off-pathway oligomers,
      that remained unexplored until recently. With the EC50 and dissociation constants
      in the low micromolar range, these heteroannulenes induce a switch in the
      secondary structure of toxic prefibrillar on-pathway oligomers of alpha-Syn,
      converting them into minimally toxic nonseeding off-pathway oligomers. The
      inhibition of the aggregation and the reduction of toxicity have been studied in
      vitro as well as inside neuroblastoma cells.

PMID- 30296046
TI  - Amorphous Phosphorus-Doped Cobalt Sulfide Modified on Silicon Pyramids for
      Efficient Solar Water Reduction.
AB  - Cobalt sulfide (CoS x) functioned as a co-catalyst to accelerate the kinetics of
      photogenerated electrons on Si photocathode, leading to the enhancement of solar
      hydrogen evolution efficiency. By doping phosphorus heteroatoms, CoS x materials
      showed an improved catalytic activity because of superior surface area and
      quantity of active sites. Furthermore, increased vacancies in unoccupied
      electronic states were observed, as more phosphorus atoms doped into CoS x co
      catalysts. Although these vacant sites improved the capability to accept
      photoinduced electrons from Si photoabsorber, chemisorption energy of atomic
      hydrogen on catalysts was the dominant factor affecting in photoelectrochemical
      performance. We suggested that P-doped CoS x with appropriate doping quantities
      showed thermoneutral hydrogen adsorption. Excess phosphorus dopants in CoS x
      contributed to excessively strong adsorption with H atoms, causing the poor
      consecutive desorption ability of photocatalytic reaction. The optimal P-doped
      CoS x-decorated Si photocathode showed a photocurrent of -20.6 mA cm-2 at 0 V.
      Moreover, a TiO2 thin film was deposited on the Si photocathode as a passivation
      layer for improving the durability. The current density of 10 nm TiO2-modified
      photocathode remained at approximately -13.3 mA cm-2 after 1 h of
      chronoamperometry.

PMID- 30296048
TI  - Catalytic Applications of Vanadium: A Mechanistic Perspective.
AB  - The chemistry of vanadium has seen remarkable activity in the past 50 years. In
      the present review, reactions catalyzed by homogeneous and supported vanadium
      complexes from 2008 to 2018 are summarized and discussed. Particular attention is
      given to mechanistic and kinetics studies of vanadium-catalyzed reactions
      including oxidations of alkanes, alkenes, arenes, alcohols, aldehydes, ketones,
      and sulfur species, as well as oxidative C-C and C-O bond cleavage, carbon-carbon
      bond formation, deoxydehydration, haloperoxidase, cyanation, hydrogenation,
      dehydrogenation, ring-opening metathesis polymerization, and oxo/imido
      heterometathesis. Additionally, insights into heterogeneous vanadium catalysis
      are provided when parallels can be drawn from the homogeneous literature.

PMID- 30296050
TI  - Water as a Universal Infrared Probe for Bioanalysis in Aqueous Solution by
      Attenuated Total Reflection-Surface Enhanced Infrared Absorption Spectroscopy.
AB  - Monitoring the properties and reactions of biomolecules at their interface has
      attracted ever-growing interest. Here, we propose an approach of infrared
      analysis technique that utilizes water molecule as a universal probe for in situ
      and label free monitoring of interfacial bioevents in aqueous solution with high
      sensitivity. The strong infrared (IR) signal of O-H stretching vibrations from
      the repelled water is used to sensitively reveal the kinetics of interfacial
      bioevents at molecular level based on the steric displacement of water using an
      attenuated total reflection-surface enhanced infrared absorption spectroscopy.
      Using interfacial immuno-recognition and DNA hybridization as demonstrations,
      water IR probe offers 26 and 34 times higher sensitivity and even 200 and 86
      times lower detection limit for immunosensing and DNA sensing, respectively, as
      compared to the traditional IR molecular fingerprints.

PMID- 30296049
TI  - Selection of Appropriate Autoinducer Analogues for the Modulation of Quorum
      Sensing at the Host-Bacterium Interface.
AB  - Bacteria regulate a variety of phenotypes in response to their population density
      using quorum sensing (QS). This phenomenon is regulated by small molecule or
      peptide signals, the best characterized of which are the N-acyl l-homoserine
      lactones (AHLs) utilized by Gram-negative bacteria. As many QS-controlled
      phenotypes, notably pathogenicity and symbiosis, can profoundly impact host
      eukaryotes, there is significant interest in developing methods for modulating QS
      signaling and either ameliorating or augmenting these phenotypes. One strategy
      has been the use of non-native AHL analogues to agonize or antagonize specific
      AHL receptors. This approach is complicated, however, by the potential for
      prospective hosts to respond to both native AHLs and synthetic analogues.
      Accordingly, identifying AHL analogues with little or no activity toward
      eukaryotes is important in developing QS modulation as a strategy for the
      regulation of prokaryotic behaviors. Herein, we utilize the model plant
      Arabidopsis thaliana to characterize eukaryotic responses to a variety of
      synthetic AHL analogues to identify structural elements of existing scaffolds
      that may elicit responses in prospective hosts. Our results indicate that, while
      many of these compounds have no discernible effect on A. thaliana, some elicit
      strong phenotypes similar to those produced by auxin, a hormone involved in
      almost all aspects of plant development. We outline concentrations and chemical
      scaffolds that are ideal for deployment on plant hosts for the regulation of QS.
      This approach should be exportable to other eukaryotes for the selection of
      optimal AHL tools for the study of QS at the host-microbe interface.

PMID- 30296051
TI  - 4,6-Diphenylpyrimidine Derivatives as Dual Inhibitors of Monoamine Oxidase and
      Acetylcholinesterase for the Treatment of Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder with multifactorial
      pathogenesis. Monoamine oxidase (MAO) and acetylcholinesterase enzymes (AChE) are
      potential targets for the treatment of AD. A total of 15 new propargyl containing
      4,6-diphenylpyrimidine derivatives were synthesized and screened for the MAO and
      AChE inhibition activities along with ROS production inhibition and metal
      chelation potential. All the synthesized compounds were found to be selective and
      potent inhibitors of MAO-A and AChE enzymes at nanomolar concentrations. VB1 was
      found to be the most potent MAO-A and BuChE inhibitor with IC50 values of 18.34
      +/- 0.38 nM and 0.666 +/- 0.03 MUM, respectively. It also showed potent AChE
      inhibition with an IC50 value of 30.46 +/- 0.23 nM. Compound VB8 was found to be
      the most potent AChE inhibitor with an IC50 value of 9.54 +/- 0.07 nM and
      displayed an IC50 value of 1010 +/- 70.42 nM against the MAO-A isoform. In the
      cytotoxic studies, these compounds were found to be nontoxic to the human
      neuroblastoma SH-SY5Y cells even at 25 MUM concentration. All the compounds were
      found to be reversible inhibitors of MAO-A and AChE enzymes. In addition, these
      compounds also showed good neuroprotective properties against 6-OHDA- and H2O2
      induced neurotoxicity in SH-SY5Y cells. All the compounds accommodate nicely to
      the hydrophobic cavity of MAO-A and AChE enzymes. In the molecular dynamics
      simulation studies, both VB1 and VB8 were found to be stable in the respective
      cavities for 30 ns. Thus, 4,6-diphenylpyrimidine derivatives can act as promising
      leads in the development of dual-acting inhibitors targeting MAO-A and AChE
      enzymes for the treatment of Alzheimer's disease.

PMID- 30296052
TI  - Dual Physically Cross-Linked kappa-Carrageenan-Based Double Network Hydrogels
      with Superior Self-Healing Performance for Biomedical Application.
AB  - Chemically linked double network (DN) hydrogels display extraordinary mechanical
      attributes but mostly suffer from poor self-healing property and unsatisfactory
      biocompatibility due to the irreversible breaks in their chemical-linked networks
      and the use of toxic chemical cross-linking agents. To address these limitations,
      we developed a novel kappa-carrageenan/polyacrylamide (KC/PAM) DN hydrogel
      through a dual physical-cross-linking strategy, with the ductile, hydrophobically
      associated PAM being the first network, and the rigid potassium ion (K+) cross
      linked KC being the second network. The dual physically cross-linked DN (DPC-DN)
      hydrogels with optimized KC concentration exhibit excellent fracture tensile
      stress (1320 +/- 46 kPa) and toughness (fracture energy: 6900 +/- 280 kJ/m3),
      comparable to those fully chemically linked DN hydrogels and physically
      chemically cross-linked hybrid DN hydrogels. Moreover, because of their unique
      dual physical-cross-linking structures, the KC/PAM hydrogels also demonstrated
      rapid self-recovery, remarkable notch-insensitivity, self-healing capability, as
      well as excellent cytocompatibility toward stem cells. Accordingly, this work
      presents a new strategy toward fabricating self-repairing DPC-DN hydrogels with
      outstanding mechanical behaviors and biocompatibility. The new type of DN
      hydrogels demonstrates strong potentiality in many challenging biomedical
      applications such as artificial diaphragm, tendon, and cartilage.

PMID- 30296053
TI  - Duplex Lateral Flow Assay for the Simultaneous Detection of Yersinia pestis and
      Francisella tularensis.
AB  - High-risk pathogens such as Francisella tularensis and Yersinia pestis are
      categorized as highly hazardous organisms that can be used as biological weapons.
      Given the extreme infectivity of these potential biowarfare agents, a rapid,
      sensitive, cost-effective, and specific method for their detection is required.
      Here, we report the multiplexed amplification detection of genomic DNA from
      Francisella tularensis and Yersinia pestis. Amplification was achieved using
      isothermal recombinase polymerase amplification, exploiting tailed primers,
      followed by detection using a nucleic-acid lateral flow assay. Excess primers
      were removed using a novel fishing strategy, avoiding the use of
      postamplification purification that requires centrifugation and infers additional
      assay cost. The entire assay is completed in less than 1 h, achieving limits of
      detection of 243 fg (1.21 * 102 genome equivalent) and 4 fg (0.85 genome
      equivalent) for Francisella tularensis and Yersinia pestis, respectively.

PMID- 30296054
TI  - Molecular Targeted NIR-II Probe for Image-Guided Brain Tumor Surgery.
AB  - Optical imaging strategies for improving delineation of glioblastoma (GBM) is
      highly desired for guiding surgeons to distinguish cancerous tissue from healthy
      and precious brain tissue. Fluorescence imaging (FLI) in the second near-infrared
      window (NIR-II) outperforms traditional NIR-I imaging with better tissue
      penetration, higher spatial and temporal resolution, and less auto fluorescence
      and scattering. Because of high expression in GBM and many other tumors,
      urokinase Plasminogen Activator Receptor (uPAR) is an attractive and well proven
      target for FLI. Herein we aim to combine the benefit of a NIR-II fluorophore with
      a high affinity uPAR targeting small peptide. A targeted NIR-II fluorescent probe
      was developed by conjugating an in-house synthesized NIR-II fluorophore, CH1055,
      and a uPAR targeting peptide, AE105. To characterize the in vivo distribution and
      targeting properties, a dynamic imaging was performed in orthotopic GBM bearing
      nude mice ( n = 8). Additionally, fluorescence guided surgery of orthotopic GBM
      was performed in living animals. CH1055-4Glu-AE105 was easily synthesized with
      >75% yield and >98% HPLC evaluated purity. The retention time of the probe on
      analytical HPLC was 15.9 min and the product was verified by mass spectrometry.
      Dynamic imaging demonstrated that the uPAR targeting probe visualized orthotopic
      GBM through the intact skull with a tumor-to-background ratio (TBR) of 2.7
      peaking at 96 h. Further, the orthotopic GBM was successfully resected in small
      animals guided by the NIR-II FLI. By using a small uPAR targeting NIR-II probe,
      FLI allows us to specifically image and detect GBM. A real-time imaging setup
      further renders FLI guided tumor resection, and the probe developed in this work
      is a promising candidate for clinical translation.

PMID- 30296055
TI  - Accelerated Carrier Relaxation through Reduced Coulomb Screening in Two
      Dimensional Halide Perovskite Nanoplatelets.
AB  - For high-speed optoelectronic applications relying on fast relaxation or energy
      transfer mechanisms, understanding of carrier relaxation and recombination
      dynamics is critical. Here, we compare the differences in photoexcited carrier
      dynamics in two-dimensional (2D) and quasi-three-dimensional (quasi-3D) colloidal
      methylammonium lead iodide perovskite nanoplatelets via differential transmission
      spectroscopy. We find that the cooling of excited electron-hole pairs by phonon
      emission progresses much faster and is intensity-independent in the 2D case. This
      is due to the low dielectric surrounding of the thin perovskite layers, for which
      the Frohlich interaction is screened less efficiently leading to higher and less
      density-dependent carrier-phonon scattering rates. In addition, rapid dissipation
      of heat into the surrounding occurs due to the high surface-to-volume ratio.
      Furthermore, we observe a subpicosecond dissociation of resonantly excited 1s
      excitons in the quasi-3D case, an effect which is suppressed in the 2D
      nanoplatelets due to their large exciton binding energies. The results highlight
      the importance of the surrounding environment of the inorganic nanoplatelets on
      their relaxation dynamics. Moreover, this 2D material with relaxation times in
      the subpicosecond regime shows great potential for realizing devices such as
      photodetectors or all-optical switches operating at THz frequencies.

PMID- 30296056
TI  - Assembly of Robust Holmium-Directed 2D Metal-Organic Coordination Complexes and
      Networks on the Ag(100) Surface.
AB  - We describe the formation of lanthanide-organic coordination networks and
      complexes under ultra-high-vacuum conditions on a clean Ag(100) surface. The
      structures comprise single Ho atoms as coordination centers and 1,4
      benzenedicarboxylate (from terephtalic acid, TPA) as molecular linkers. Using low
      temperature scanning tunneling microscopy, we find two different chiral phases of
      surface-supported metal-organic structures incorporating Ho atoms. Density
      functional theory calculations can explain the structure of both binding motifs
      and give possible reasons for their varying formation under the respective Ho/TPA
      ratios, as well as deposition and annealing temperatures. Metal-ligand
      interactions drive the formation of cloverleaf-shaped mononuclear Ho-TPA4
      complexes establishing supramolecular arrays stabilized through hydrogen bonding.
      A 2D lanthanide-organic reticulation is observed when changing the stoichiometry
      between the two building blocks. The combined insights from scanning tunneling
      microscopy and density functional theory reveal the relative stability, charge
      transfer, and bonding environment of both motifs.

PMID- 30296057
TI  - Molecular Colocalization Using Massive Gold Cluster Secondary Ion Mass
      Spectrometry.
AB  - We report on the ion emission from impacts of hypervelocity massive gold clusters
      for use in secondary ion mass spectrometry. Two massive gold clusters are
      considered, 520 keV Au4004+ and 1040 keV Au28008+. The emission of fragment ions
      and molecular ions is evaluated for a series of neat samples, glycine,
      phenylalanine, arginine, and gramicidin S. A 2 to 4-fold increase of molecular
      ion emission is observed from impacts of 1040 keV Au28008+ versus 520 keV
      Au4004+. Compared to impacts of 20 keV Ar2000+ and 20 keV (H2O)7000+ in static
      conditions, impacts of 1040 keV Au28008+ display a 6 to 9-fold increase in the
      number of detected molecular ions per projectile impact. To explain the increased
      emission of molecular species, we examine the size of the impact craters and
      calculate the ratio of molecular ions to fragment ions. The characterization of
      Au28008+ and the operating conditions of the gold liquid metal ion source are
      presented.

PMID- 30296058
TI  - Hierarchically Designed Ag@Ce6Mo10O39 Marigold Flower-Like Architectures: An
      Efficient Electrode Material for Hybrid Supercapacitors.
AB  - We facilely prepared silver nanoparticle-decorated Ce6Mo10O39 marigold flower
      like structures (Ag NPs@CM MFs) for use as an effective positive material in
      hybrid supercapacitors (HSCs). With the aid of ethylenediaminetetraacetic acid
      (EDTA) as a chelating agent, self-assembled CM MFs were synthesized by a single
      step hydrothermal method. When the electrochemical properties were tested in an
      aqueous alkaline electrolyte, the synthesized CM MFs with 0.15 g of EDTA
      exhibited a relatively high charge storage property (55.3 MUA h/cm2 at 2 mA/cm2)
      with a battery-type redox behavior. The high capacity performance is mainly
      because of the large surface area of the CM MFs, and the hierarchically connected
      nanoflakes provide wide open wells for rapid accessibility of electrolyte ions
      and enable fast transportation of electrons. A further improvement in
      electrochemical performance was achieved (62 MUA h/cm2 at 2 mA/cm2) by decorating
      Ag NPs on the surface of the CM MFs (i.e., Ag NPs@CM MFs), which is attributed to
      the increased electric conductivity. Considering the synergistic effect and the
      high electrochemical activity, Ag NPs@CM MFs were further employed as an
      effective positive electrode for the fabrication of pouch-type HSC with porous
      carbon (negative electrode) in an alkaline electrolyte. The HSC exhibited a high
      cell potential (1.5 V) with maximum energy and power densities of 0.0183 mW h/cm2
      and 10.237 mW/cm2, respectively. The potency of HSC in practical applications was
      also demonstrated by energizing red and yellow light-emitting diodes as well as a
      three-point pattern torch light.

PMID- 30296059
TI  - Microfluidic-Based Genosensor To Detect Human Papillomavirus (HPV16) for Head and
      Neck Cancer.
AB  - High-risk human papillomavirus (HPV) infection, mainly with HPV16 type, has been
      increasingly considered as an important etiologic factor in head and neck
      cancers. Detection of HPV16 is therefore crucial for these types of cancer, but
      clinical tests are not performed routinely in public health systems owing to the
      high cost and limitations of the existing tests. In this article, we report on a
      potentially low-cost genosensor capable of detecting low concentrations of HPV16
      in buffer samples and distinguishing, with high accuracy, head and neck cancer
      cell lines according to their HPV16 status. The genosensor consisted of a
      microfluidic device that had an active layer of a HPV16 capture DNA probe
      (cpHPV16) deposited onto a layer-by-layer film of chitosan and chondroitin
      sulfate. Impedance spectroscopy was the principle of detection utilized, leading
      to a limit of detection of 10.5 pM for complementary ssDNA HPV16 oligos
      (ssHPV16). The genosensor was also able to distinguish among HPV16+ and HPV16-
      cell lines, using the multidimensional projection technique interactive document
      mapping. Hybridization between the ssHPV16 oligos and cpHPV16 probe was confirmed
      with polarization-modulated infrared reflection-absorption spectroscopy, where
      PO2 and amide I and amide II bands from adenine and thymine were monitored. The
      electrical response could be modeled as resulting from an adsorption process
      represented in a Freundlich model. Because the fabrication procedures of the
      microfluidic devices and genosensors and the data collection and analysis can be
      implemented at low cost, the results presented here amount to a demonstration of
      possible routine screening for HPV infections.

PMID- 30296060
TI  - Insertions within the Saxitoxin Biosynthetic Gene Cluster Result in Differential
      Toxin Profiles.
AB  - The neurotoxin saxitoxin and related paralytic shellfish toxins are produced by
      multiple species of cyanobacteria and dinoflagellates. This study investigates
      the two saxitoxin-producing strains of Scytonema crispum, CAWBG524 and CAWBG72,
      isolated in New Zealand. Each strain was previously reported to have a distinct
      paralytic shellfish toxin profile, a rare observation between strains within the
      same species. Sequencing of the saxitoxin biosynthetic clusters ( sxt) from S.
      crispum CAWBG524 and S. crispum CAWBG72 revealed the largest sxt gene clusters
      described to date. The distinct toxin profiles of each strain were correlated to
      genetic differences in sxt tailoring enzymes, specifically the open-reading frame
      disruption of the N-21 sulfotransferase sxtN, adenylylsulfate kinase sxtO, and
      the C-11 dioxygenase sxtDIOX within S. crispum CAWBG524 via genetic insertions.
      Heterologous overexpression of SxtN allowed for the proposal of saxitoxin and 3'
      phosphoadenosine 5'-phosphosulfate as substrate and cofactor, respectively, using
      florescence binding assays. Further, catalytic activity of SxtN was confirmed by
      the in vitro conversion of saxitoxin to the N-21 sulfonated analog gonyautoxin 5,
      making this the first known report to biochemically confirm the function of a sxt
      tailoring enzyme. Further, SxtN could not convert neosaxitoxin to its N-21
      sulfonated analog gonyautoxin 6, indicating paralytic shellfish toxin
      biosynthesis most likely occurs along a predefined route. In this study, we
      identified key steps toward the biosynthetic conversation of saxitoxin to other
      paralytic shellfish toxins.

PMID- 30296061
TI  - Ultrafine Particle Emissions from Natural Gas, Biogas, and Biomethane Combustion.
AB  - Biogas and biomethane (=purified biogas) are major renewable fuels that play a
      pivotal role in the evolving global energy economy. Here, we measure ultrafine
      particle (UFP; Dp (particle diameter) < 100 nm) emissions from the combustion of
      biomethane and biogas produced from five different representative sources: two
      food waste digesters, two dairy waste digesters, and one landfill. Combustion
      exhaust for each of these sources is measured from one or more representative
      sectors including electricity generation, motor vehicles, and household use.
      Results show that UFP emissions are similar when using biomethane and natural gas
      with similar sulfur and siloxane content. Approximately 70% of UFPs emitted from
      water heaters and cooking stoves were semivolatile, but 30% of the UFPs were
      nonvolatile and did not evaporate even under extremely high dilution conditions.
      Photochemical aging of biomethane combustion exhaust and natural gas combustion
      exhaust produced similar amounts of secondary organic aerosol (SOA) formation.
      The results of the current study suggest that widespread adoption of biogas and
      biomethane as a substitute for natural gas will not significantly increase
      ambient concentrations of primary and secondary UFPs if advanced combustion
      technology is used and the sulfur and siloxane content is similar for
      biogas/biomethane and natural gas.

PMID- 30296063
TI  - X-ray Crystallographic Structure of a Teixobactin Derivative Reveals Amyloid-like
      Assembly.
AB  - This paper describes the X-ray crystallographic structure of a derivative of the
      antibiotic teixobactin and shows that its supramolecular assembly through the
      formation of antiparallel beta-sheets creates binding sites for oxyanions. An
      active derivative of teixobactin containing lysine in place of allo
      enduracididine assembles to form amyloid-like fibrils, which are observed through
      a thioflavin T fluorescence assay and by transmission electron microscopy. A
      homologue, bearing an N-methyl substituent, to attenuate fibril formation, and an
      iodine atom, to facilitate X-ray crystallographic phase determination,
      crystallizes as double helices of beta-sheets that bind sulfate anions. beta
      Sheet dimers are key subunits of these assemblies, with the N-terminal
      methylammonium group of one monomer and the C-terminal macrocycle of the other
      monomer binding each anion. These observations suggest a working model for the
      mechanism of action of teixobactin, in which the antibiotic assembles and the
      assemblies bind lipid II and related bacterial cell wall precursors on the
      surface of Gram-positive bacteria.

PMID- 30296064
TI  - Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells
      Using Metabolic Intermediates.
AB  - The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the
      enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of
      cellular physiology. Metabolic labeling strategies to monitor O-GlcNAcylation in
      cells have proven of great value for uncovering the molecular roles of O-GlcNAc.
      These strategies rely on two-step labeling procedures, which limits the scope of
      experiments that can be performed. Here, we report on the creation of fluorescent
      uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N
      acyl group of glucosamine is modified with a suitable linker and fluorophore.
      Using human OGT, we show these donor sugar substrates permit direct monitoring of
      OGT activity on protein substrates in vitro. We show that feeding cells with a
      corresponding fluorescent metabolic precursor for the last step of the hexosamine
      biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O
      GlcNAcylated proteins within live cells. This one-step metabolic feeding strategy
      permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine
      nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose
      dependent manner. Because no genetic engineering of cells is required, we
      anticipate this strategy should be generally amenable to studying the roles of O
      GlcNAc in cellular physiology as well as to gain an improved understanding of the
      regulation of OGT within cells. The further expansion of this one-step in-cell
      labeling strategy should enable performing a range of experiments including two
      color pulse chase experiments and monitoring OGT activity on specific protein
      substrates in live cells.

PMID- 30296065
TI  - Pretreatment with gamma-Valerolactone/[Mmim]DMP and Enzymatic Hydrolysis on
      Corncob and Its Application in Immobilized Butyric Acid Fermentation.
AB  - Corncob is a widely available raw material with high carbohydrate and low lignin
      content. To improve corncob conversion to the fermentable sugars, a novel method
      encompassing pretreatment using the gamma-valerolactone (GVL)/1-methyl-3
      methylimidazolium dimethylphosphite ([Mmim]DMP) system integrated with cellulase
      hydrolysis was developed and optimized. It is confirmed that lignin was extracted
      efficiently after combined pretreatment and that the subsequent enzymatic
      saccharification efficiency could be significantly enhanced, resulting in the
      yield of 94.9% glucose from cellulose and 53.3% xylose from xylan, respectively.
      Furthermore, the above fermentable sugars were used as carbon source for
      Clostridium tyrobutyricum immobilized in macroporous Ca-alginate-lignin beads
      with the extracted lignin as the active ingredient to evaluate the fermentability
      of butyric acid. The results showed that high butyrate productivity of 0.47 g/L/h
      and yield of 0.45 g/g were obtained after 10 repeated batches of fermentation,
      demonstrating an effective process for the production of butyric acid from
      abundant corncob waste-biomass.

PMID- 30296066
TI  - Facile Mechanosynthesis of the Archetypal Zn-Based Metal-Organic Frameworks.
AB  - Mechanochemical methods have been successful in providing rapid access to a
      number of inorganic-organic functional materials under mild conditions. Recently,
      we demonstrated a novel mechanochemical strategy for metal-organic framework
      (MOF) preparation based on predesigned oxo-centered secondary building units.
      Herein, we develop this method for the facile preparation of the isoreticular MOF
      (IRMOF) family members based on a combination of an oxozinc amidate cluster,
      [Zn4(MU4-O)(NHOCPh)6], and selected ditopic aminoterephthalate and 4,4'
      biphenyldicarboxylate as well as tritopic 1,3,5-benzenetribenzoate ligands. The
      resulting IRMOF-3, IRMOF-10, and MOF-177 crystalline materials were characterized
      using powder X-ray diffraction, IR spectroscopy, scanning electron microscopy
      (SEM), and thermogravimetric analysis. We found that the character of the organic
      linker strongly affects the nature of the resulting MOF crystallites after
      activation processes. The SEM images demonstrate that IRMOF-3 formed
      microcrystallites in the range of 400-500 nm, while the two other materials
      exhibited microstructures of amorphous phases. The porosity of each sample was
      estimated by N2 sorption measurements at 77 K. These results provide an efficient
      and general method for the mechanosynthesis of Zn-based MOF materials using a
      predesigned oxozinc cluster.

PMID- 30296067
TI  - Mechanism for O-O Bond Formation via Radical Coupling of Metal and Ligand Based
      Radicals: A New Pathway.
AB  - Artificial photosynthesis carries promise to deliver abundant clean energy for
      the needs of a growing population. Deep mechanistic understanding is required to
      achieve rational design of fast and durable water oxidation catalysts. Here we
      provided first evidence for a new mechanism of the O-O bond formation via radical
      coupling of the oxidized metal?oxo of radicaloid character (RuIV?O) and ligand
      based radical ([ligand-NO]+* cation radical). O-O bond formation is facilitated
      via spin alignment and takes place via a virtually barrier less pathway inside
      the single metal complex. In situ reactive intermediate conversion was monitored
      by mass spectrometry, resonance Raman (RR) and EPR. Computational analysis have
      shown that the formation of [ligand-NO]+* happens at a lower overpotential than
      the formation of the [RuV?O(ligand)]3+ intermediate. Overall, the presented
      paradigm for O-O bond formation opens new opportunities for rational catalyst
      design.

PMID- 30296068
TI  - Comparative Site-Specific N-Glycosylation Analysis of Lactoperoxidase from
      Buffalo and Goat Milk Using RP-UHPLC-MS/MS Reveals a Distinct Glycan Pattern.
AB  - The N-glycan pattern of lactoperoxidase (LPO) from buffalo and goat milk was
      analyzed with the corresponding site of attachment. The enzyme was purified from
      whey on cation exchange chromatography, proteolyzed using chymotrypsin, and the
      resulting (glyco)peptides were directly analyzed on reverse phase ultrahigh
      performance liquid chromatography coupled to ESI-Q-TOF MS in tandem mode. N
      Glycans such as high mannose, complex, and hybrid types were identified in
      buffalo and goat LPO. Among sialylated complex and hybrid types, the terminal
      Neu5Ac linked to either LacNAc/LacdiNAc found exclusively in buffalo, whereas
      Neu5Gc linked to LacdiNAc was predominant in goat LPO. N-Glycans at Asn6 and
      Asn349 in buffalo LPO were completely core fucosylated, while these sites in goat
      LPO showed differential fucosylation. Differential occupancy was observed at
      Asn112 with or without nonfucosylated complex and hybrid types, whereas mainly
      high mannose glycans were found in Asn222 in both of the LPOs. The presence of
      glycan isomers in buffalo and goat LPO was also observed. Despite the presence of
      distinct complex and hybrid glycans, the common glycosylation features in buffalo
      and goat LPO were identified and are comparable with those of bovine LPO. This
      finding could be useful in exploring the beneficial role of these glycans as
      functional ingredients for food products.

PMID- 30296069
TI  - Electric Field Processing: Novel Perspectives on Allergenicity of Milk Proteins.
AB  - Milk proteins are being widely used in formulated foods as a result of their
      excellent technological, functional, and biological properties. However, the most
      representative proteins from casein and whey fractions are also recognized as
      major allergens and responsible for the prevalence of cow's milk protein allergy
      in childhood. Electroheating technologies based on thermal processing of food as
      a result of application of moderate electric fields, also known by ohmic heating
      (OH) or Joule effect, are establishing a solid foothold in the food industry.
      Currently, the influence of OH on allergenic aspects of milk proteins is under
      debate but still undisclosed. The occurrence of electrical effects on the protein
      structure and its function has already been reported; thus, the impact of OH over
      allergenicity should not be overlooked. On the basis of these recent findings, it
      is then relevant to speculate about the impact of this emergent technology on the
      potential allergenicity of milk proteins.

PMID- 30296070
TI  - Computation-Aided Rational Deletion of C-Terminal Region Improved the Stability,
      Activity, and Expression Level of GH2 beta-Glucuronidase.
AB  - In this study, computation-aided design on the basis of structural analysis was
      employed to rationally identify a highly dynamic C-terminal region that regulates
      the stability, expression level, and activity of a GH2 fungal glucuronidase from
      Aspergillus oryzae Li-3 (PGUS). Then, four mutants with a precisely truncated C
      terminal region in different lengths were constructed; among them, mutant D591
      604 with a 3.8-fold increase in half-life at 65  degrees C and a 6.8 kJ/mol
      increase in Gibbs free energy showed obviously improved kinetic and thermodynamic
      stability in comparison to PGUS. Mutants D590-604 and D591-604 both showed
      approximately 2.4-fold increases in the catalytic efficiency kcat/ Km and 1.8
      fold increases in the expression level. Additionally, the expression level of
      PGUS was doubled through a C-terminal region swap with bacterial GUS from E. coli
      (EGUS). Finally, the robust PGUS mutants D590-604 and D591-604 were applied in
      the preparation of glycyrrhetinic acid with 4.0- and 4.4-fold increases in
      concentration through glycyrrhizin hydrolysis by a fed-batch process.

PMID- 30296071
TI  - Scalable and Rechargeable Antimicrobial Coating for Food Safety Applications.
AB  - Environmental surfaces are common avenues for microbial contamination and
      transmission in food-processing establishments. We recently synthesized a polymer
      that combines both N-halamine and dopamine functional groups to form a novel
      antimicrobial coating material. A series of chemical (titration) and biological
      ("sandwich" and anti-inhabitation) tests were designed to prove the stability and
      functionality of as-developed coating material. Halamine-dopamine polymer-coated
      stainless-steel surface inactivated 6 log10 CFU of both Staphylococcus aureus and
      Escherichia coli O157:H7 under experimental detection limit within 10 min of
      contact time. After three "discharge-recharge" cycles, the surface maintained the
      same antimicrobial effectiveness; 60% of the surface chlorine remained after 10
      "discharge-recharge" cycles. In addition, the coating thickness and chlorine
      content could be further tuned through adjusting the formulation of the coating.
      We also demonstrated that this coating material could be easily scaled up to
      apply on real food equipment parts through a spray-coating method. Thus our
      polymer material has great potential to produce a high-performance, low-cost, and
      easy-to-apply coating on food-associated environmental surfaces for food safety
      preventive-control applications.

PMID- 30296072
TI  - Antifungal Polyamides of Hydroxycinnamic Acids from Sunflower Bee Pollen.
AB  - The aim of the bioassay-guided fractionation was the selection of the most potent
      group of compounds responsible for the protection of sunflower bee pollen grains.
      Synthesis of prospective antifungal polyamides of hydroxycinnamic acids was based
      on previous structural elucidation of ethanol soluble fraction by 1H,1H-PFG-COSY,
      1H,13C-HSQC, FT-IR, FT-Raman, and LC-MS experiments. The main compounds found
      were tri- p-coumaroylspermidines accompanied by other HCAA of spermidine and
      putrescine. Several model HCAA derivatives were prepared to test their antifungal
      activity against widespread spoilage fungi ( A. niger 42 CCM 8189, F. culmorum
      DMF 0103, and P. verrucosum DMF 0023). A. niger CCM 8189 and F. culmorum DMF 0103
      exhibited higher resistance to the antifungal effects of hydroxycinnamic acid
      amides, whereas P. verrucosum DMF 0023 was the most sensitive strain. It has been
      discovered the effect of HCAA polarity on the role of secondary metabolites in
      the microbial protection of pollen grains. The combination of bioassay-guided
      fractionation, structural elucidation, selection of prospective compounds, and
      their synthesis to determine their antifungal properties could be considered as
      an original approach.

PMID- 30296073
TI  - Ni-Catalyzed Reductive Coupling of Electron-Rich Aryl Iodides with Tertiary Alkyl
      Halides.
AB  - This work illustrates the reductive coupling of electron-rich aryl halides with
      tertiary alkyl halides under Ni-catalyzed cross-electrophile coupling conditions,
      which offers an efficient protocol for the construction of all carbon quaternary
      stereogenic centers. The mild and easy-to-operate reaction tolerates a wide range
      of functional groups. The utility of this method is manifested by the preparation
      of cyclotryptamine derivatives, wherein successful incorporation of 7-indolyl
      moieties is of particular interest as numerous naturally occurring products are
      composed of these key scaffolds. DFT calculations have been carried out to
      investigate the proposed radical chain and double oxidative addition pathways,
      which provide useful mechanistic insights into the part of the reaction that
      takes place in solution.

PMID- 30296074
TI  - Photoinduced Charge-Transfer Dynamics in WO3/BiVO4 Photoanodes Probed through
      Midinfrared Transient Absorption Spectroscopy.
AB  - The dynamics of photopromoted electrons in BiVO4, WO3, and WO3/BiVO4
      heterojunction electrodes has been directly probed by transient absorption (TA)
      midinfrared (mid-IR) spectroscopy in the picosecond to microsecond time range. By
      comparison of the dynamics recorded with the two individual oxides at 2050 cm-1
      with that of the heterojunction system after excitation at different wavelengths,
      electron-transfer processes between selectively excited BiVO4 and WO3 have been
      directly tracked for the first time. These results support the charge carrier
      interactions which were previously hypothesized by probing the BiVO4 hole
      dynamics through TA spectroscopy in the visible range. Nanosecond mid-IR TA
      experiments confirmed that charge carrier separation occurs in WO3/BiVO4
      electrodes under visible-light excitation, persisting up to the microsecond time
      scale.

PMID- 30296075
TI  - Modification and Cross-Linking of Proteins by Glycolaldehyde and Glyoxal: A Model
      System.
AB  - Highly reactive intermediates of the Maillard reaction, such as glycolaldehyde
      and glyoxal, are precursors in the modification and cross-linking of proteins.
      Therefore, we investigated ribonuclease A modified by glycolaldehyde and glyoxal,
      separately. For the first time, various protein species derived by these
      aldehydes were successfully separated by ion-exchange chromatography and gel
      permeation chromatography. Highly cross-linked ribonuclease A was obtained in
      glycolaldehyde incubations. In contrast, glyoxal predominantly led to modified
      monomeric protein species. These results were verified by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and isoelectric focusing. Quantitation of mono
      and bivalent protein modifications of the isolated protein species led to a
      positive correlation between the degree of protein modification and the change of
      the isoelectric point and molecular weight, respectively. Glycolaldehyde is
      easily oxidized to glyoxal. However, significantly lower levels of bivalent
      glyoxal modifications were detected in glycolaldehyde versus glyoxal incubations
      (glyoxal-lysine dimer, 1.58 +/- 0.02 versus 2.86 +/- 0.04 mmol/mol of
      phenylalanine; glyoxal-lysine amide, 2.7 +/- 0.1 versus 5.6 +/- 0.1 mmol/mol of
      phenylalanine). In addition, a novel glycolaldehyde-specific lysine-lysine cross
      link was identified and putatively assigned as 1-(5-amino-5-carboxypentyl)-4-(5
      amino-5-carboxypentyl-amino)pyridinium salt.

PMID- 30296076
TI  - Induction of Human-Lung-Cancer-A549-Cell Apoptosis by 4-Hydroperoxy-2-decenoic
      Acid Ethyl Ester through Intracellular ROS Accumulation and the Induction of
      Proapoptotic CHOP Expression.
AB  - Royal jelly, a natural product secreted by honeybees, contains several fatty
      acids, such as 10-hydroxy-2-decenoic acid (DE), and shows anti- and pro-apoptotic
      properties. 4-Hydroperoxy-2-decenoic acid ethyl ester (HPO-DAEE), a DE
      derivative, exhibits potent antioxidative activity; however, it currently remains
      unclear whether HPO-DAEE induces cancer-cell death. In the present study,
      treatment with HPO-DAEE induced human-lung-cancer-A549-cell death (52.7 +/-
      10.2%) that was accompanied by DNA fragmentation. Moreover, the accumulation of
      intracellular reactive oxygen species (ROS, 2.38 +/- 0.1-fold) and the induction
      of proapoptotic CCAAT-enhancer-binding-protein-homologous-protein (CHOP)
      expression (18.4 +/- 4.0-fold) were observed in HPO-DAEE-treated cells. HPO-DAEE
      elicited CHOP expression and cell death were markedly suppressed by pretreatment
      with N-acetylcysteine (NAC), an antioxidant, by 2.40 +/- 1.57-fold and 5.7 +/-
      1.6%, respectively. Pretreatment with 4-phenylbutyric acid (PBA), an inhibitor of
      endoplasmic reticulum stress, also suppressed A549-cell death (38.4 +/- 1.1%).
      Furthermore, we demonstrated the involvement of extracellular-signal-regulated
      protein kinase (ERK) and p38-related signaling in HPO-DAEE-elicited cell-death
      events. Overall, we concluded that HPO-DAEE induces A549-cell apoptosis through
      the ROS-ERK-p38 pathway and, at least in part, the CHOP pathway.

PMID- 30296077
TI  - Fast Access to Amphiphilic Multiblock Architectures by the Anionic
      Copolymerization of Aziridines and Ethylene Oxide.
AB  - An ideal system for stimuli-responsive and amphiphilic (block) polymers would be
      the copolymerization of aziridines with epoxides. However, to date, no
      copolymerization of these two highly strained three-membered heterocycles had
      been achieved. Herein, we report the combination of the living oxy- and
      azaanionic ring-opening polymerization of ethylene oxide (EO) and sulfonamide
      activated aziridines. In a single step, well-defined amphiphilic block copolymers
      are obtained by a one-pot copolymerization. Real-time 1H NMR spectroscopy
      revealed the highest difference in reactivity ratios ever reported for an anionic
      copolymerization (with r1 = 265 and r2 = 0.004 for 2-methyl- N-tosylaziridine/EO
      and r1 = 151 and r2 = 0.013 for 2-methyl- N-mesylaziridine/EO), leading to the
      formation of block copolymers with monomodal and moderate molecular weight
      distributions ( Mw/ Mn mostly <=1.3). The amphiphilic diblock copolymers were
      used to stabilize emulsions and to prepare polymeric nanoparticles by
      miniemulsion polymerization, representing a novel class of nonionic and
      responsive surfactants. In addition, this unique comonomer reactivity of
      activated-Az/EO allows fast access to multiblock copolymers, and we prepared the
      first amphiphilic penta- or tetrablock copolymers containing aziridines in only
      one or two steps, respectively. These examples render the combination of epoxide
      and aziridine copolymerizations via a powerful strategy for producing
      sophisticated macromolecular architectures and nanostructures.

PMID- 30296078
TI  - The Structural Arrangement and Relative Abundance of Aliphatic Units May Effect
      Long-Wave Absorbance of Natural Organic Matter as Revealed by 1H NMR
      Spectroscopy.
AB  - The objective of this study was to shed light on structural features which
      underlay intensity of long wave absorbance of natural organic matter (NOM) using
      1H NMR spectroscopy. For this purpose, a set of the NOM samples was assembled
      from arctic and nonarctic sampling sites (the Kolyma river basin and Moscow
      region, respectively). It was to ensure a substantial difference in the
      humification degree of the isolated organic matter-the biogeochemical proxy of
      the long-wave absorbance of NOM. The assembled NOM set was analyzed using
      solution-state 1H NMR spectroscopy. The distribution of both backbone and
      exchangeable protons was determined using acquisition of spectra in three
      different solvents. The substantially higher contribution of nonfunctionalized
      aliphatic moieties CHn (e.g., materials derived from linear terpenoids, MDLT) in
      the arctic NOM samples was revealed as compared to the nonarctic ones. The latter
      were characterized with the higher content of CHalpha protons adjacent to
      electron-withdrawing groups which belong to carboxyl rich alicyclic moieties
      (CRAMs) or to aromatic constituents of NOM. We have calculated a ratio of CHn to
      CHalpha protons as a structural descriptor which showed significant inverse
      correlation to intensity of long wave absorbance assessed with a use of E4/ E6
      ratio and the slope of absorption spectrum. The steric hindrance of aromatic
      chromophoric groups of the NOM ensemble by bulky nonfunctionalized aliphatic
      moieties (e.g., MDLT) was set as a hypothesis for explanation of this phenomenon.
      The bulky aliphatics might increase a distance between the interacting groups
      resulting in inhibition of electronic (e.g., charge-transfer) interactions in the
      NOM ensemble. The obtained relationships were further explored using Fourier
      transform mass spectrometry as complementary technique to 1H NMR spectroscopy.
      The data obtained on correlation of molecular composition of NOM with 1H NMR data
      and optical properties were very supportive of our hypothesis that capabilities
      of NOM ensemble of charge transfer interactions can be dependent on structural
      arrangement and relative abundance of nonabsorbing aliphatic moieties.

PMID- 30296079
TI  - Domestic Fowl Breed Variation in Egg White Protein Expression: Application of
      Proteomics and Transcriptomics.
AB  - Avian egg white is essential for protecting and nourishing bird embryos during
      their development. Being produced in the female magnum, variability in hen
      oviduct gene expression may affect egg white composition in domestic chickens.
      Since traditional poultry breeds may represent a source of variation, in the
      present study we describe the egg white proteome (mass spectrometry) and
      corresponding magnum transcriptome (high-throughput sequencing) for 20 hens from
      five domestic fowl breeds (large breeds: Araucana, Czech golden pencilled,
      Minorca; and small breeds: Booted bantam, Rosecomb bantam). In total, we
      identified 189 egg white proteins and 16391 magnum-expressed genes. The majority
      of egg white protein content comprised proteins with an antimicrobial function.
      Despite general similarity, Between-class Principal Component Analysis revealed
      significant breed-specific variability in protein abundances, differentiating
      especially small and large breeds. Though we found strong association between
      magnum mRNA expression and egg white protein abundance across genes, coinertia
      analysis revealed no transcriptome/proteome costructure at the individual level.
      Our study is the first to show variation in protein abundances in egg white
      across chicken breeds with potential effects on egg quality, biosafety, and chick
      development. The observed interindividual variation probably results from post
      transcriptional regulation creating a discrepancy between proteomic and
      transcriptomic data.

PMID- 30296081
TI  - Controlling Structure Beyond the Initial Coordination Sphere: Complexation
      Induced Reversed Micelle Formation in Calix[4]pyrrole-Containing Diblock
      Copolymers.
AB  - A diblock copolymer containing a strapped calix[4]pyrrole-based ion pair
      recognition subunit has been synthesized via RAFT polymerization. As prepared,
      the polymer is hydrophobic and devoid of any particular morphological form.
      However, upon ion pair complexation, the copolymer self-assembles to generate
      reverse micelles in organic media. The reverse micelles formed in this way may be
      used to extract alkali cation and cesium halide anion salts from an aqueous
      source into an organic receiving phase. The polymer proved more effective as an
      extractant than the corresponding free ion pair receptor.

PMID- 30296080
TI  - Formation and Stability of Core-Shell Nanofibers by Electrospinning of Gel-Like
      Corn Oil-in-Water Emulsions Stabilized by Gelatin.
AB  - Core-shell nanofibers were fabricated by electrospinning of gel-like corn oil
      emulsions stabilized by gelatin. The oil-in-water (O/W) emulsions satisfied the
      Herschel-Bulkley rheological model and showed shear-thinning and predominantly
      elastic gel behaviors. The increasing oil fractions (phi) ranging from 0 to 0.6
      remarkably increased the apparent viscosity and then led to an increase in the
      average diameter and encapsulation efficiency of electrospun fibers. Core-shell
      structured fibers by emulsion electrospinning were observed in transmission
      electron microscopy (TEM) images. The encapsulated oil was found to randomly
      distribute as core, especially inside the beads. The binding of corn oil to
      gelatin was mainly driven by noncovalent forces. These core-shell fibers at
      various phi values (phi = 0.2, 0.4, 0.6, and 0.8) showed a high thermal
      decomposition stability upon heating to 250  degrees C, and the denaturation
      temperatures were 85.32  degrees C, 77.97  degrees C, 82.99  degrees C, and 87.25
      degrees C, respectively. The corn oil encapsulated in emulsion-based fiber mats
      had good storage stability during 5 days. These results contributed to a good
      understanding of emulsion electrospinning of food materials for potential
      applications in bioactive encapsulation, enzyme immobilization, and active food
      packaging.

PMID- 30296082
TI  - Antiradical Activity and Mechanism of Coumarin-Chalcone Hybrids: Theoretical
      Insights.
AB  - In view of the multifunctional features of coumarins and chalcones, coumarin
      chalcone hybrids have attracted much attention in recent years. Herein, the free
      radical scavenging activities of a series of coumarin-chalcone hybrids were
      investigated using the density functional theory (DFT) method. Three main
      reaction mechanisms were explored: hydrogen atom transfer (HAT), electron
      transfer followed by proton transfer (SET-PT), and sequential proton loss
      electron transfer (SPLET). Thermodynamic descriptors associated with these
      mechanisms were calculated in the gas phase and solvents. The results demonstrate
      that the predicted antioxidant efficiencies are generally in accordance with the
      experimental results. HAT is proposed as the thermodynamically favored mechanism
      in the gas phase and nonpolar solution, while SPLET is preferred in polar media.
      Our results indicate that compound MPHCC possesses potential for inactivating
      free radicals via double HAT and double SPLET mechanisms depending upon the
      polarity of environment. In addition, the SPLHAT mechanism provides an
      alternative pathway to HAT and SPLET for radical scavenging by MPHCC and OPHCC.
      The results confirmed the crucial role of hydroxyl groups on the chalcone moiety
      in trapping radicals. 4'-OH in the catechol group is proposed as the primary
      target for radical attack.

PMID- 30296084
TI  - Simple Entropy Terms for End-Point Binding Free Energy Calculations.
AB  - We introduce a number of computationally inexpensive modifications to the MM/PBSA
      and MM/GBSA estimators for binding free energies, which are based on average
      receptor-ligand interaction energies in simulations of a noncovalent complex, to
      improve the treatment of entropy: second- and higher-order terms in a cumulant
      expansion and a confining potential on ligand external degrees of freedom. We
      also consider a filter for snapshots where ligands have drifted from the initial
      binding pose. The variations were tested on six sets of systems for which binding
      modes and free energies have previously been experimentally determined. For some
      data sets, none of the tested estimators led to results significantly correlated
      with measured free energies. In data sets with nontrivial correlation, a ligand
      RMSD cutoff of 3 A and a second-order truncation of the cumulant expansion was
      found to be comparable or better than the average interaction energy by several
      statistical metrics.

PMID- 30296083
TI  - Irpeksins A-E, 1,10- seco-Eburicane-Type Triterpenoids from the Medicinal Fungus
      Irpex lacteus and Their Anti-NO Activity.
AB  - Five new triterpenoids, irpeksins A-E (1-5), were isolated from fruiting bodies
      of the medicinal fungus Irpex lacteus. The structures as well as absolute
      configurations of the new compounds were established via extensive spectroscopic
      analysis, computational methods, and Cotton effects. Compounds 1-4 are featured
      by a scaffold of 1,10- seco- and ring B aromatic eburicane (24-methyllanostane),
      and compound 5 is characterized by a scaffold of 1,10-9,11- diseco- and ring B
      aromatic eburicane, which represents unprecedented cleavage patterns in the
      lanostane family. Compounds 1-5 showed significant inhibitory activity against NO
      production in LPS-activated RAW 264.7 macrophage cells with IC50 values varying
      from 2.2 to 19.6 MUM.

PMID- 30296085
TI  - Pd/PTABS: Low Temperature Etherification of Chloroheteroarenes.
AB  - A mild, general, and highly efficient catalytic etherification protocol for
      chloroheteroarenes was developed using the Pd/PTABS catalytic system. The
      protocol is selective for the etherification of chloroheteroarenes using a large
      variety of electron-rich and electron-deficient phenol bearing synthons which
      include inter alia biologically and commercially important estrone, estradiol,
      tyrosine, and several other molecules. The mildness of the new protocol is
      expected to be beneficial for the synthesis of complex drugs and drug
      intermediates offering late-stage modification of bioactive compounds.

PMID- 30296086
TI  - Orally Absorbed Derivatives of the beta-Lactamase Inhibitor Avibactam. Design of
      Novel Prodrugs of Sulfate Containing Drugs.
AB  - Only one FDA-approved beta-lactamase inhibitor has ever been orally available:
      clavulanic acid, approved in 1984. Avibactam, approved by FDA in 2015, is the
      first of a new class of BLIs called diazabicyclooctanes, or "DBOs". This class
      has much broader coverage than clavulanic acid but can only be administered by
      intravenous injection. Herein, we describe the synthesis and testing of the first
      approved BLI to be rendered orally bioavailable since clavulanic acid (1984).

PMID- 30296087
TI  - Calculating Optical Rotatory Dispersion Spectra in Solution Using a Smooth
      Dielectric Model.
AB  - The calculation of specific rotation of molecules in solution is probed at the
      coupled cluster (CC) level utilizing a continuum dielectric model based on a
      definition of the dielectric permittivity as a smooth function of electron
      density. Solvation effects are captured through polarization of Hartree-Fock (HF)
      molecular orbitals before subsequent calculations with the coupled cluster
      singles and doubles (CCSD) method. For the challenging ( S)-methyloxirane
      molecule, CCSD specific rotations yield an incorrect sign for the rotation in
      water, and the continuum model is unable to predict the wide variations in the
      optical rotatory dispersion (ORD) curves seen for nonpolar solvents of similar
      dielectric constant. In two molecules, (1 S,4 S)-norbornenone and ( S)-2
      chloropropionitrile, specific rotations computed with CCSD in conjunction with
      implicit solvent fail to provide solvent shifts of the correct order of
      magnitude, indicating that the solvent response is a major contribution to the
      overall solvation effect.

PMID- 30296088
TI  - Flat-Histogram Monte Carlo as an Efficient Tool To Evaluate Adsorption Processes
      Involving Rigid and Deformable Molecules.
AB  - Monte Carlo simulations are the foundational technique for predicting
      thermodynamic properties of open systems where the process of interest involves
      the exchange of particles. Thus, they have been used extensively to
      computationally evaluate the adsorption properties of nanoporous materials and
      are critical for the in silico identification of promising materials for a
      variety of gas storage and chemical separation applications. In this work we
      demonstrate that a well-known biasing technique, known as "flat-histogram"
      sampling, can be combined with temperature extrapolation of the free energy
      landscape to efficiently provide significantly more useful thermodynamic
      information than standard open ensemble MC simulations. Namely, we can accurately
      compute the isosteric heat of adsorption and number of particles adsorbed for
      various adsorbates over an extremely wide range of temperatures and pressures
      from a set of simulations at just one temperature. We extend this derivation of
      the temperature extrapolation to adsorbates with intramolecular degrees of
      freedom when Rosenbluth sampling is employed. Consequently, the working capacity
      and isosteric heat can be computed for any given combined temperature/pressure
      swing adsorption process for a large range of operating conditions with both
      rigid and deformable adsorbates. Continuous thermodynamic properties can be
      computed with this technique at very moderate computational cost, thereby
      providing a strong case for its application to the in silico identification of
      promising nanoporous adsorbents.

PMID- 30296089
TI  - Vibronic Coupling in the First Five Electronic States of Dicyanodiacetylene
      Radical Cation.
AB  - We examine vibronic coupling in the first five electronic states (X2Pig-A2Piu
      B2Sigmag+-C2Sigmau+-D2Pig-E2Piu) of dicyanodiacetylene radical cation (C6N2*+) in
      this article. Prompted by the prediction of its existence in the astrophysical
      environment, the vibronic band structure of these electronic states of C6N2*+ has
      been probed in spectroscopic measurements in laboratory by various groups.
      Inspired by numerous experimental data, we undertook the task of investigating
      topographical details of electronic potential energy surfaces, their coupling
      mechanism and nuclear dynamics on them. The degenerate Pi electronic states of
      this radical are prone to Renner-Teller instability, and in addition symmetry
      allowed Sigma-Pi and Pi-Pi vibronic coupling is expected to play crucial role in
      the detailed vibronic structure of each of the above electronic states. A
      vibronic coupling model is developed here and first-principles nuclear dynamics
      study is carried out employing quantum mechanical methods. The vibronic band
      structure thus calculated is compared with experimental results and the
      progressions are identified and assigned. The nonradiative internal conversion
      dynamics among electronic states is also examined and discussed in relation to
      the various coupling of electronic states.

PMID- 30296090
TI  - Nitric Oxide Sensing through 1,2,3,4-Oxatriazole Formation from Acylhydrazide: A
      Kinetic Study.
AB  - A simple molecular probe displays highly selective turn-on response toward NO by
      the unprecedented NO-induced formation of a 1,2,3,4-oxatriazole ring exhibiting
      no interference from various endogenous biomolecules including DHA, AA, etc.
      Kinetics of the reactions between NO and the probe provide a mechanistic insight
      into the formation of 1,2,3,4-oxatriazole which showed that, though initially
      1,2,3,4-oxatriazole is formed and extractable in solid form, it exists in
      equilibrium with the ring opened azide form which ultimately hydrolyzed and
      converted to carboxylic acid and nitrate. The reaction displays second-order
      dependence on [NO] and first-order on [Probe]. The probe is water-soluble, cell
      permeable, and noncytotoxic and appropriates for live cell imaging. This
      constitutes the first report where there is a direct evidence of NO-induced ring
      closing reaction of an acyl hydrazide moiety leading to the formation of 1,2,3,4
      oxatriazole.

PMID- 30296091
TI  - Role of H Transfer in the Gas-Phase Sulfidation Process of MoO3: A Quantum
      Molecular Dynamics Study.
AB  - Layered transition metal dichalcogenide (TMDC) materials have received great
      attention because of their remarkable electronic, optical, and chemical
      properties. Among typical TMDC family members, monolayer MoS2 has been considered
      a next-generation semiconducting material, primarily due to a higher carrier
      mobility and larger band gap. The key enabler to bring such a promising MoS2
      layer into mass production is chemical vapor deposition (CVD). During CVD
      synthesis, gas-phase sulfidation of MoO3 is a key elementary reaction, forming
      MoS2 layers on a target substrate. Recent studies have proposed the use of gas
      phase H2S precursors instead of condensed-phase sulfur for the synthesis of
      higher-quality MoS2 crystals. However, reaction mechanisms, including atomic
      level reaction pathways, are unknown for MoO3 sulfidation by H2S. Here, we report
      first-principles quantum molecular dynamics (QMD) simulations to investigate gas
      phase sulfidation of MoO3 flake using a H2S precursor. Our QMD results reveal
      that gas-phase H2S molecules efficiently reduce and sulfidize MoO3 through the
      following reaction steps: Initially, H transfer occurs from the H2S molecule to
      low molecular weight Mo xO y clusters, sublimated from the MoO3 flake, leading to
      the formation of molybdenum oxyhydride clusters as reaction intermediates. Next,
      two neighboring hydroxyl groups on the oxyhydride cluster preferentially react
      with each other, forming water molecules. The oxygen vacancy formed on the Mo-O-H
      cluster as a result of this dehydration reaction becomes the reaction site for
      subsequent sulfidation by H2S that results in the formation of stable Mo-S bonds.
      The identification of this reaction pathway and Mo-O and Mo-O-H reaction
      intermediates from unbiased QMD simulations may be utilized to construct reactive
      force fields (ReaxFF) for multimillion-atom reactive MD simulations.

PMID- 30296093
TI  - Three-Input Molecular Keypad Lock Based on a Norbornadiene-Quadricyclane
      Photoswitch.
AB  - The photo- and acidochromic properties of a new generation norbornadiene
      derivative have been harnessed for the realization of a three-input keypad lock,
      where a specific sequence of inputs induces a unique output. Reversible
      quadricyclane/norbornadiene photoisomerization is reported, and this rare feature
      allows the first example of a norbornadiene-based molecular logic system. The
      function of this system is clearly rationalized in terms of the interconversion
      scheme and the absorption spectra of the involved species.

PMID- 30296094
TI  - Connecting the Dunham Expansion to the Dissociation Limit for Interatomic
      Potentials: Application to Lennard-Jones m- n Potentials.
AB  - Dunham generated the expansion for energy levels of a rotating, vibrating
      diatomic molecule from an expansion of the potential about the equilibrium
      position. For partition functions, however, the energy levels are needed all the
      way to dissociation. Analytic Morse oscillator energies are not very useful
      because the exponential decay of the Morse potential is much too short-ranged for
      any physical system. The longer-range Lennard-Jones 12-6 potential could be used,
      but quantum energies have not previously been conveniently fit. I show how Dunham
      coefficients begin a set of asymptotic functions for any interaction potential,
      one function arising from each successive term in the WKB expansion. I apply this
      to the family of Lennard-Jones m- n (LJ m- n) potentials with an R-m repulsive
      term and R-n attractive term ( m > n) and demonstrate how m can be used as a
      parameter to adjust either the equilibrium distance or harmonic frequency. I
      present an empirical parametrization of LJ m- n vibrotor energies starting with
      Dunham coefficients generated from four terms in the WKB expansion. This
      information is combined with data from numerically solved energies and asymptotic
      limits to fit the functions all the way to dissociation. One can also treat exp-6
      and similar model potentials with different repulsive parts using the same method
      because the expansion form is controlled by the long-range part of the potential.

PMID- 30296092
TI  - Shear Viscosity Computed from the Finite-Size Effects of Self-Diffusivity in
      Equilibrium Molecular Dynamics.
AB  - A method is proposed for calculating the shear viscosity of a liquid from finite
      size effects of self-diffusion coefficients in Molecular Dynamics simulations.
      This method uses the difference in the self-diffusivities, computed from at least
      two system sizes, and an analytic equation to calculate the shear viscosity. To
      enable the efficient use of this method, a set of guidelines is developed. The
      most efficient number of system sizes is two and the large system is at least
      four times the small system. The number of independent simulations for each
      system size should be assigned in such a way that 50%-70% of the total available
      computational resources are allocated to the large system. We verified the method
      for 250 binary and 26 ternary Lennard-Jones systems, pure water, and an ionic
      liquid ([Bmim][Tf2N]). The computed shear viscosities are in good agreement with
      viscosities obtained from equilibrium Molecular Dynamics simulations for all
      liquid systems far from the critical point. Our results indicate that the
      proposed method is suitable for multicomponent mixtures and highly viscous
      liquids. This may enable the systematic screening of the viscosities of ionic
      liquids and deep eutectic solvents.

PMID- 30296095
TI  - Conical Intersections Induced by Quantum Light: Field-Dressed Spectra from the
      Weak to the Ultrastrong Coupling Regimes.
AB  - In classical laser fields with frequencies resonant with the electronic
      excitation in molecules, it is by now known that conical intersections are
      induced by the field and are called light-induced conical intersections (LICIs).
      As optical cavities have become accessible, the question arises whether their
      quantized modes could also lead to the appearance of LICIs. A theoretical
      framework is formulated for the investigation of LICIs of diatomics in such
      quantum light. The eigenvalue spectrum of the dressed states in the cavity is
      studied, putting particular emphasis on the investigation of absorption spectra
      of the Na2 molecule, that is, on the transitions between dressed states, measured
      by employing a weak probe pulse. The dependence of the spectra on the light
      matter coupling strength in the cavity and on the frequency of the cavity mode is
      studied in detail. The computations demonstrate strong nonadiabatic effects
      caused by the appearing LICI.

PMID- 30296096
TI  - Insight into The Nature of Rim Bonds in Coronene.
AB  - Coronene is known in chemistry as an aromatic or even superaromatic molecule
      while it has 24 pi-electrons which does not conform to the 4 n + 2 Huckel's rule.
      Chemical bonding description of it is not settled in chemistry and five models
      were reported in the literature. According to our model, coronene has two
      concentric pi-systems responsible for aromaticity inside of the molecule. In
      addition to that there are six peripheral 2c-2e pi-bonds, which makes coronene
      aliphatic/aromatic at the same time. However, recent experiments and calculations
      put in question the presence of peripheral pi-bonds. In order to resolve this
      issue, we computationally studied reaction mechanism of the Cl2 molecule with
      C2H4, C6H6, and C24H12. As it turned out, coronene behaves in a way similar to
      ethylene by adding Cl2 molecule. Thus, it proves that coronene indeed has
      peripheral double bonds which is also consistent with its experimental
      geometrical features. Our chemical bonding model allows to identify the most
      reactive atoms in coronene and other PAHs; therefore, it is a matter of
      importance for combustion and soot formation studies.

PMID- 30296097
TI  - Precision Medicine: Role of Proteomics in Changing Clinical Management and Care.
AB  - It is now possible to collect large sums of health-related data which has the
      potential to transform healthcare. Proteomics, with its central position as
      downstream of genetics and epigenetic inputs and upstream of biochemical outputs
      and integrators of environmental signals, is well-positioned to contribute to
      health discoveries and management. We present our perspective on the role of
      proteomics and other Omics in precision health and medicine.

PMID- 30296098
TI  - Einstein's Viscosity Equation for Nanolubricated Friction.
AB  - The generalized Einstein equation for the viscosity of a dispersion/suspension,
      MU = (1 + alphafphi)MU0, where MU0 is the liquid viscosity, phi is the solid
      volume fraction, and alphaf is a coefficient, is applied to the viscosity of a
      nanofluid lubricant. The coefficient of lubricated friction in the hydrodynamic
      regime is proportional to the viscosity of the lubricant. Therefore, an equation
      for the coefficient of friction with nanofluid lubrication can be formulated. We
      present such an equation and show its validity for common types of bearings
      (journal, rolling, and ball bearings). The equation, which may be viewed as one
      of nanofriction laws, is compared with experimental results for WS2 nanoparticle
      enhanced oil lubrication, showing agreement within 7% accuracy.

PMID- 30296099
TI  - Study of Short-Chain Alcohol and Alcohol-Water Adsorption in MEL and MFI
      Zeolites.
AB  - In this paper, we present a comparative study of the adsorption behavior of short
      chain alcohols (pure and in aqueous solution) into silicalite-1 (MFI-type
      zeolite) and silicalite-2 (MEL-type zeolite). For quite some time, silicalite-1
      has been the reference material to address the problem of adsorptive-based
      separation, mostly for hydrocarbon mixtures. Interestingly, being structurally
      close to silicalite-1, adsorption studies using silicalite-2 are scarce and to
      the best of our knowledge, a comparative study of their behavior for alcohol
      water mixtures has not been published to date. We have here resorted to molecular
      simulation techniques to analyze the adsorption and diffusion phenomena in both
      zeolites at 25 and 50  degrees C for pure methanol, ethanol, 1-butanol, and
      water, and for some relevant compositions of alcohol/water mixtures. In addition
      to the dilute regime in the mixture, our study ranges from intermediate alcohol
      concentrations to alcohol-rich phases, relevant to alcohol purification
      processes. Besides, we have performed volumetric and calorimetric measurements of
      single-component adsorption of alcohols in pure silica MEL zeolite, which were
      used to validate the model potentials used in the simulations. We observe that
      the zigzag channels of MFI zeolite are most likely responsible for its somewhat
      higher affinity for alcohols. This leads to higher adsorption selectivities when
      compared to those of MEL zeolite. We have also found that the choice of water
      model strongly conditions water coadsorption into the zeolites and subsequently
      the predictions of the adsorbent's selectivity in alcohol/water systems. Despite
      considerable differences for adsorbed pure components, diffusivities of alcohol
      and water adsorbed from mixtures are relatively similar, as a consequence of the
      strong hydrogen bonds between hydroxyl groups and water.

PMID- 30296100
TI  - Exploring Hybrid Imogolite Nanotube Formation via Si/Al Stoichiometry Control.
AB  - Hybrid imogolite aluminosilicate nanotubes with methylated internal surface can
      be obtained by introduction of the corresponding organosilane during their
      synthesis. However, similarly to pristine imogolite, a number of side products,
      including proto-imogolite (open-imoLS), allophanes, and aluminum hydroxides, are
      formed, which ultimately impact on the properties of the dispersions. In order to
      minimize the proportion of these side products, we have here systematically
      explored the impact of the initial Si/Al ratio on the content of hybrid imogolite
      dispersions before and after dialysis. By combining cryo-transmission electron
      microscopy, inductively coupled plasma mass spectrometry, infrared spectroscopy,
      and small-angle X-ray scattering, we evidenced that the Si/Al ratio has a large
      impact on the formation of aluminum hydroxides that can be minimized with a
      slight excess of Si precursor. However, a large excess of Si is detrimental to
      the reaction yield leading to an important proportion of proto-imogolite. We
      propose that the optimal Si/Al ratio of ca. 0.6 can both minimize the proportion
      of aluminum hydroxides and proto-imogolite. These results suggest that the
      dynamic and therefore reactive character of imogolite dispersions may have been
      so far underlooked.

PMID- 30296101
TI  - DLVO Interaction Energies for Hollow Particles: The Filling Matters.
AB  - A thorough knowledge of the interaction energy between a hollow particle (HP) and
      a surface or between two HPs is critical to the optimization of HP-based products
      and assessing the environmental risks of HPs and HP-associated pollutants. The
      van der Waals (vdW) energy between a HP and a surface is often calculated by
      subtracting the vdW energies of the inner and outer HP geometries. In this study,
      we show that this subtraction method is only valid when the interior and exterior
      fluids are the same, for example, for water-filled HPs (WHPs) dispersed in an
      aqueous solution. Expressions were developed to calculate the vdW energies for
      HPs whose interiors were filled with air (AHPs). The vdW energies were then
      calculated between a planar surface and a spherical or cylindrical WHP and AHP,
      and between WHPs or AHPs. The vdW attraction between a surface and a WHP was
      decreased at large separation distances compared to solid particles, and this
      reduced the depth of the secondary minimum. In contrast, the vdW attraction for
      AHPs and a surface was significantly reduced at all separation distances, and
      even became repulsive for thin shells, and this inhibited both primary and
      secondary minimum interactions. The vdW attraction between WHPs decreased with
      increasing shell thicknesses, and this reduced aggregation in both primary and
      secondary minima. In contrast, aggregation of AHPs was increased in both minima
      with decreasing shell thicknesses because of an increase in vdW attraction. Our
      theoretical calculations show the evolution of vdW and total interaction energies
      for HPs with different interior fluids and shell thicknesses. These results help
      explain various experimental observations such as inhibited attachment and
      favorable aggregation for AHPs (e.g., carbon nanotubes) and favorable bubble
      coalescence.

PMID- 30296102
TI  - Theoretical Study on Molten Alkali Carbonate Interfaces.
AB  - The properties and structure of relevant interfaces involving molten alkali
      carbonates are studied using molecular dynamics simulation. Lithium carbonate and
      the Li/Na/K carbonate eutectic mixture are considered. Gas phases composed of
      pure CO2 or a model flue gas mixture are analyzed. Similarly, the adsorption of
      these gas phases on graphene are studied, showing competitive CO2 and N2
      adsorption that develops liquid-like layers and damped oscillation behavior for
      density. The interaction of the studied carbonates with graphene is also
      characterized by development of adsorption layers through strong graphene
      carbonate interactions and the development of hexagonal lattice arrangements,
      especially for lithium carbonate. The development of molten salts-vacuum
      interfaces is also considered, analyzing the ionic rearrangement in the
      interfacial region. The behavior of the selected gas phases on top of molten
      alkyl carbonate is also studied, showing the preferential adsorption of CO2
      molecules when flue gases are considered.

PMID- 30296103
TI  - Synthesis of Isomeric Perylenodithiophene Diimides.
AB  - Two isoelectronic dithiophene-fused perylene diimides (PDTI-1 and PDTI-2) were
      synthesized via a " bay-derivatization toward lateral extension" strategy. Single
      crystal analysis unambiguously confirmed their unique structures and packing
      arrangements. The new PDTI system manifested significantly red-shifted
      absorptions with intense bands at 500-700 nm. Further dimerization indicated the
      potential of these dithiophene-fused PDIs as new building blocks for the
      construction of versatile rylene dyes in optoelectronic devices.

PMID- 30296104
TI  - Partitioning of Size-Mismatched Impurities to Grain Boundaries in 2d Solid Hard
      Sphere Monolayers.
AB  - Computational studies have been carried out to investigate the equilibrium
      partitioning of size-mismatched impurities between the bulk solid and grain
      boundary (GB) environments in 2d hard-sphere monolayers. The solvent repacking
      Monte Carlo method and a new variation were used to exchange varying numbers and
      types of particles under conditions of fixed particle fugacities, allowing
      efficient sampling of impurity particle distributions even within the bulk solid.
      Measurements of GB stiffness depression arising from the impurities were made via
      the capillary fluctuation method and found to agree with calculations based on
      the Gibbs adsorption isotherm, providing a test of the internal consistency of
      the results. The dependence of the excess concentration at the GB on factors,
      including impurity size (diameter ratios lambda = 0.5-4 times the majority host
      particle diameter), impurity concentration, grain misorientation angle, and
      packing pressure, was studied. In general, the affinity of impurity particles for
      GB increased with the difference between their size and the host particles, and
      varied with grain misorientation angle with a dependence reflecting the excess
      free area at the GB. Impurities with lambda = 4 were exceptions to both these
      trends, due to their ability to substitute efficiently for six-coordinate host
      particles within the bulk and for five-coordinate host particles at dislocations
      in the grain boundaries. Comparison with results from an experimental study of
      mixed colloidal monolayers raises questions about how kinetic effects during
      grain coarsening might produce less impurity segregation to the GB than
      equilibrium exchange.

PMID- 30296105
TI  - Surfaces with Dual Functionality through Specific Coimmobilization of Self
      Assembled Polymeric Nanostructures.
AB  - Coimmobilization of functional, nanosized assemblies broadens the possibility to
      engineer dually functionalized active surfaces with a nanostructured texture.
      Surfaces decorated with different nanoassemblies, such as micelles, polymersomes,
      or nanoparticles are in high demand for various applications ranging from
      catalysis, biosensing up to antimicrobial surfaces. Here, we present a
      combination of bio-orthogonal and catalyst-free strain-promoted azide-alkyne
      click (SPAAC) and thiol-ene reactions to simultaneously coimmobilize various
      nanoassemblies; we selected polymersome-polymersome and polymersome-micelle
      assemblies. For the first time, the immobilization method using SPAAC reaction
      was studied in detail to attach soft, polymeric assemblies on a solid support.
      Together, the SPAAC and thiol-ene reactions successfully coimmobilized two unique
      self-assembled structures on the surfaces. Additionally, poly(dimethylsiloxane)
      (PDMS)-based polymersomes were used as "ink" for direct immobilization from a
      PDMS-based microstamp onto a surface creating locally defined patterns. Combining
      immobilization reactions has the advantage to attach any kind of nanoassembly
      pairs, resulting in surfaces with "desired" interfacial properties. Different
      nanoassemblies that encapsulate multiple active compounds coimmobilized on a
      surface will pave the way for the development of multifunctional surfaces with
      controlled properties and efficiency.

PMID- 30296106
TI  - Poor Man's Atomic Layer Deposition of LiF for Additive-Free Growth of Lithium
      Columns.
AB  - Lithium metal is an ideal material for high-energy, cost-effective rechargeable
      energy storage systems. The thermodynamically unfavorable solid-liquid interface
      between the lithium metal and organic electrolyte necessitates the formation of
      an interlayer (SEI) which is known to have significant impact on lithium
      morphologies. Less well understood is the impact of the current collector
      substrate on the morphology of electrodeposited lithium. Here we report on the
      morphology of electrodeposited lithium as a function of the chemical
      pretreatments of the working electrode. We find that a copper substrate
      pretreatment with acidic solutions (sulfuric, oxalic, or acetic acid) results in
      the deposition of close-packed lithium columns with a uniform diameter. A
      controlled study of the pre-electrodeposited copper surface indicates that the
      formation of a 5-8 nm thick LiF protective layer on copper substrate from a
      chemical reaction between adsorbed surface water layer in acidic solutions and
      LiPF6 electrolyte is the key process in the electrochemical growth of lithium
      columns. We anticipate that this simple chemical approach can be generalized as a
      scalable, low-cost, additive-free substrate treatment method for depositing a LiF
      protective layer, broadly applicable in the development of uniform lithium films.

PMID- 30296107
TI  - Ultrathin van der Waals Metalenses.
AB  - Ultrathin and flat optical lenses are essential for modern optical imaging,
      spectroscopy, and energy harvesting. Dielectric metasurfaces comprising nanoscale
      quasi-periodic resonator arrays are promising for such applications, as they can
      tailor the phase, amplitude, and polarization of light at subwavelength
      resolution, enabling multifunctional optical elements. To achieve 2pi phase
      coverage, however, most dielectric metalenses need a thickness comparable to the
      wavelength, requiring the fabrication of high-aspect-ratio scattering elements.
      We report ultrathin dielectric metalenses made of van der Waals (vdW) materials,
      leveraging their high refractive indices and the incomplete phase design approach
      to achieve device thicknesses down to ~lambda/10, operating at infrared and
      visible wavelengths. These materials have generated strong interest in recent
      years due to their advantageous optoelectronic properties. Using vdW metalenses,
      we demonstrate near-diffraction-limited focusing and imaging and exploit their
      layered nature to transfer the fabricated metalenses onto flexible substrates to
      show strain-induced tunable focusing. Our work enables further downscaling of
      optical elements and opportunities for the integration of metasurface optics in
      ultraminiature optoelectronic systems.

PMID- 30296108
TI  - Avalanche Behavior in Creep Failure of Disordered Materials.
AB  - We present a mesoscale elastoplastic model of creep in disordered materials,
      which considers temperature-dependent stochastic activation of localized
      deformation events that are coupled by internal stresses, leading to collective
      avalanche dynamics. We generalize this stochastic plasticity model by introducing
      damage in terms of a local strength that decreases, on statistical average, with
      increasing local plastic strain. The model captures failure in terms of strain
      localization in a catastrophic shear band concomitant with a finite-time
      singularity of the creep rate. The statistics of avalanches in the run-up to
      failure is characterized by a decreasing avalanche exponent tau that, at failure,
      approaches the value tau=1.5 typical of a critical branching process. The average
      avalanche rate exhibits an inverse Omori law as a function of time to failure.
      The distribution of interavalanche times turns out to be consistent with the
      epidemic-type aftershock sequences (ETAS) model of earthquake statistics.

PMID- 30296109
TI  - Enhancing the Radiation Resistance of Undulator Permanent Magnets by Tilting the
      Easy Axis of Magnetization.
AB  - The undulator is a magnetic device usually consisting of a series of rare-earth
      permanent magnets (REPMs) arranged to generate a sinusoidal magnetic field, and
      is installed in synchrotron radiation and free electron laser facilities to
      periodically deflect high-energy electrons. Because the undulator is operated
      under a high-radiation environment, it is important to take possible measures to
      avoid the quality degradation, in particular the radiation damage of REPMs. We
      present a simple scheme to enhance the radiation resistance of REPMs in
      undulators, in which the easy axis of each REPM is tilted by 45 degrees .
      Experimental studies have revealed that the radiation resistance of REPMs in this
      configuration is enhanced by an order of magnitude compared to that in the
      conventional undulator.

PMID- 30296110
TI  - Observation of Nonlocal Heat Flux Using Thomson Scattering.
AB  - Nonlocal heat flux was measured in laser-produced coronal plasmas using a novel
      Thomson scattering technique. The measured heat flux was smaller than the
      classical values inferred from the measured plasma conditions in regions with
      large temperature gradients and agreed with classical values for weak gradients.
      Vlasov-Fokker-Planck simulations self-consistently calculated the electron
      distribution functions used to reproduce the measured Thomson scattering spectra
      and to determine the heat flux. Multigroup nonlocal simulations overestimated the
      measured heat flux.

PMID- 30296111
TI  - Erratum: GW170104: Observation of a 50-Solar-Mass Binary Black Hole Coalescence
      at Redshift 0.2 [Phys. Rev. Lett. 118, 221101 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.118.221101.

PMID- 30296112
TI  - Hybrid Systems for the Generation of Nonclassical Mechanical States via Quadratic
      Interactions.
AB  - We present a method to implement two-phonon interactions between mechanical
      resonators and spin qubits in hybrid setups, and show that these systems can be
      applied for the generation of nonclassical mechanical states even in the presence
      of dissipation. In particular, we demonstrate that the implementation of a two
      phonon Jaynes-Cummings Hamiltonian under coherent driving of the qubit yields a
      dissipative phase transition with similarities to the one predicted in the model
      of the degenerate parametric oscillator: beyond a certain threshold in the
      driving amplitude, the driven-dissipative system sustains a mixed steady state
      consisting of a "jumping cat," i.e., a cat state undergoing random jumps between
      two phases. We consider realistic setups and show that, in samples within reach
      of current technology, the system features nonclassical transient states,
      characterized by a negative Wigner function, that persist during timescales of
      fractions of a second.

PMID- 30296114
TI  - Many-Body Quantum Interference and the Saturation of Out-of-Time-Order
      Correlators.
AB  - Out-of-time-order correlators (OTOCs) have been proposed as sensitive probes for
      chaos in interacting quantum systems. They exhibit a characteristic classical
      exponential growth, but saturate beyond the so-called scrambling or Ehrenfest
      time tau_{E} in the quantum correlated regime. Here we present a path-integral
      approach for the entire time evolution of OTOCs for bosonic N-particle systems.
      We first show how the growth of OTOCs up to tau_{E}=(1/lambda)logN is related to
      the Lyapunov exponent lambda of the corresponding chaotic mean-field dynamics in
      the semiclassical large-N limit. Beyond tau_{E}, where simple mean-field
      approaches break down, we identify the underlying quantum mechanism responsible
      for the saturation. To this end we express OTOCs by coherent sums over
      contributions from different mean-field solutions and compute the dominant many
      body interference term amongst them. Our method further applies to the
      complementary semiclassical limit h->0 for fixed N, including quantum-chaotic
      single- and few-particle systems.

PMID- 30296113
TI  - Direct Measurement of Anharmonic Decay Channels of a Coherent Phonon.
AB  - We report channel-resolved measurements of the anharmonic coupling of the
      coherent A_{1g} phonon in photoexcited bismuth to pairs of high wave vector
      acoustic phonons. The decay of a coherent phonon can be understood as a
      parametric resonance process whereby the atomic displacement periodically
      modulates the frequency of a broad continuum of modes. This coupling drives
      temporal oscillations in the phonon mean-square displacements at the A_{1g}
      frequency that are observed across the Brillouin zone by femtosecond x-ray
      diffuse scattering. We extract anharmonic coupling constants between the A_{1g}
      and several representative decay channels that are within an order of magnitude
      of density functional perturbation theory calculations.

PMID- 30296115
TI  - Quantum Spin Dynamics in a Normal Bose Gas with Spin-Orbit Coupling.
AB  - In this Letter, we investigate spin dynamics of a two-component Bose gas with
      spin-orbit coupling realized in cold atom experiments. We derive coupled
      hydrodynamic equations for number and spin densities as well as their associated
      currents. Specializing to the quasi-one-dimensional situation, we obtain analytic
      solutions of the spin helix structure and its dynamics in both adiabatic and
      diabatic regimes. In the adiabatic regime, the transverse spin decays
      parabolically in the short-time limit and exponentially in the long-time limit,
      depending on initial polarization. In contrast, in the diabatic regime,
      transverse spin density and current oscillate in a way similar to the charge
      current oscillation in an undamped LC circuit. The effects of Rabi coupling on
      the short-time spin dynamics is also discussed. Finally, using realistic
      experimental parameters for ^{87}Rb, we show that the timescales for spin
      dynamics is of the order of milliseconds to a few seconds and can be observed
      experimentally.

PMID- 30296116
TI  - Tumbling of Inertial Fibers in Turbulence.
AB  - Anisotropic particles play a major role in many environmental and industrial
      turbulent flows. The modeling of their rotation dynamics is a fundamental
      challenge which has some important consequences in industrial processes, such as
      in the paper making industry. This study investigates the rotation rate of
      neutrally buoyant fibers longer than the Kolmogorov length eta_{K}. We show that
      the fiber inertia is at the origin of a decrease of the rotation rate. We propose
      a model which describes this phenomenon. We introduce also a new Stokes number
      which defines the limit of validity of the classical slender body approximation.

PMID- 30296117
TI  - Anomalous Phonon Lifetime Shortening in Paramagnetic CrN Caused by Spin-Lattice
      Coupling: A Combined Spin and Ab Initio Molecular Dynamics Study.
AB  - We study the mutual coupling of spin fluctuations and lattice vibrations in
      paramagnetic CrN by combining atomistic spin dynamics and ab initio molecular
      dynamics. The two degrees of freedom are dynamically coupled, leading to
      nonadiabatic effects. Those effects suppress the phonon lifetimes at low
      temperature compared to an adiabatic approach. The dynamic coupling identified
      here provides an explanation for the experimentally observed unexpected
      temperature dependence of the thermal conductivity of magnetic semiconductors
      above the magnetic ordering temperature.

PMID- 30296118
TI  - 21-cm Fluctuations from Charged Dark Matter.
AB  - The epoch of the formation of the first stars, known as the cosmic dawn, has
      emerged as a new arena in the search for dark matter. In particular, the first
      claimed 21-cm detection exhibits a deeper global absorption feature than
      expected, which could be caused by a low baryonic temperature, and has been
      interpreted as a sign for electromagnetic interactions between baryons and dark
      matter. This hypothesis has a striking prediction: large temperature anisotropies
      sourced by the velocity-dependent cooling of the baryons. However, in order to
      remain consistent with the rest of cosmological observations, only part of the
      dark matter is allowed to be charged and thus interactive. Here we compute, for
      the first time, the 21-cm fluctuations caused by a charged subcomponent of the
      dark matter, including both the pre- and postrecombination evolution of all
      fluids. We find that, for the same parameters that can explain the anomalous 21
      cm absorption signal, any percent-level fraction of charged dark matter would
      source novel 21-cm fluctuations with a unique acoustic spectrum, and with an
      amplitude above any other known effects. These fluctuations are uncorrelated with
      the usual adiabatic anisotropies, and would be observable at high significance
      with interferometers such as the Low-Frequency Array and the Hydrogen Epoch of
      Reionization Array, thus providing a novel probe of dark matter at cosmic dawn.

PMID- 30296120
TI  - Cycling Tames Power Fluctuations near Optimum Efficiency.
AB  - According to the laws of thermodynamics, no heat engine can beat the efficiency
      of a Carnot cycle. This efficiency traditionally comes with vanishing power
      output and practical designs, optimized for power, generally achieve far less.
      Recently, various strategies to obtain Carnot's efficiency at large power were
      proposed. However, a thermodynamic uncertainty relation implies that steady-state
      heat engines can operate in this regime only at the cost of large fluctuations
      that render them immensely unreliable. Here, we demonstrate that this unfortunate
      trade-off can be overcome by designs operating cyclically under quasistatic
      conditions. The experimentally relevant yet exactly solvable model of an
      overdamped Brownian heat engine is used to illustrate the formal result. Our
      study highlights that work in cyclic heat engines and that in quasistatic ones
      are different stochastic processes.

PMID- 30296119
TI  - Thermal Critical Points and Quantum Critical End Point in the Frustrated Bilayer
      Heisenberg Antiferromagnet.
AB  - We consider the finite-temperature phase diagram of the S=1/2 frustrated
      Heisenberg bilayer. Although this two-dimensional system may show magnetic order
      only at zero temperature, we demonstrate the presence of a line of finite
      temperature critical points related to the line of first-order transitions
      between the dimer-singlet and -triplet regimes. We show by high-precision quantum
      Monte Carlo simulations, which are sign-free in the fully frustrated limit, that
      this critical point is in the Ising universality class. At zero temperature, the
      continuous transition between the ordered bilayer and the dimer-singlet state
      terminates on the first-order line, giving a quantum critical end point, and we
      use tensor-network calculations to follow the first-order discontinuities in its
      vicinity.

PMID- 30296121
TI  - Complexity Growth Rate in Lovelock Gravity.
AB  - Using the complexity=action framework, we compute the late time growth of
      complexity for charged black holes in Lovelock gravity. Our calculation is
      facilitated by the fact that the null boundaries of the Wheeler-DeWitt patch do
      not contribute at late times and essential contributions coming from the joints
      are now understood. The late time growth rate reduces to a difference of internal
      energies associated with the inner and outer horizons, and in the limit where the
      mass is much larger than the charge, we reproduce the celebrated result of 2M/pi
      with corrections proportional to the highest Lovelock coupling in even (boundary)
      dimensions. We find in some cases a minimum mass below which complexity remains
      effectively constant, even if the black hole contains a nondegenerate horizon.

PMID- 30296122
TI  - Invisible Neutrino Decay Could Resolve IceCube's Track and Cascade Tension.
AB  - The IceCube Neutrino Observatory detects high energy astrophysical neutrinos in
      two event topologies: tracks and cascades. Since the flavor composition of each
      event topology differs, tracks and cascades can be used to test the neutrino
      properties and the mechanisms behind the neutrino production in astrophysical
      sources. Assuming a conventional model for the neutrino production, the IceCube
      data sets related to the two channels are in >3sigma tension with each other.
      Invisible neutrino decay with lifetime tau/m=10^{2}  s/eV solves this tension.
      Noticeably, it leads to an improvement over the standard nondecay scenario of
      more than 3sigma while remaining consistent with all other multimessenger
      observations. In addition, our invisible neutrino decay model predicts a
      reduction of 59% in the number of observed nu_{tau} events which is consistent
      with the current observational deficit.

PMID- 30296123
TI  - Quantum Nonlinear Optics in Atomically Thin Materials.
AB  - We show that a nonlinear optical response associated with a resonant, atomically
      thin material can be dramatically enhanced by placing it in front of a partially
      reflecting mirror, rendering otherwise weakly nonlinear systems suitable for
      experiments and applications involving quantum nonlinear optics. Our approach
      exploits the nonlinear response of long-lived polariton resonances that arise at
      particular distances between the material and the mirror. The scheme is entirely
      based on free-space optics, eliminating the need for cavities or complex
      nanophotonic structures. We analyze a specific implementation based on exciton
      polariton resonances in two-dimensional semiconductors and discuss the role of
      imperfections and loss.

PMID- 30296124
TI  - Stability of Periodically Driven Topological Phases against Disorder.
AB  - In recent experiments, time-dependent periodic fields are used to create exotic
      topological phases of matter with potential applications ranging from quantum
      transport to quantum computing. These nonequilibrium states, at high driving
      frequencies, exhibit the quintessential robustness against local disorder similar
      to equilibrium topological phases. However, proving the existence of such
      topological phases in a general setting is an open problem. We propose a
      universal effective theory that leverages on modern free probability theory and
      ideas in random matrices to analytically predict the existence of the topological
      phase for finite driving frequencies and across a range of disorder. We find
      that, depending on the strength of disorder, such systems may be topological or
      trivial and that there is a transition between the two. In particular, the theory
      predicts the critical point for the transition between the two phases and
      provides the critical exponents. We corroborate our results by comparing them to
      exact diagonalizations for driven-disordered 1D Kitaev chain and 2D Bernevig
      Hughes-Zhang models and find excellent agreement. This Letter may guide the
      experimental efforts for exploring topological phases.

PMID- 30296125
TI  - Mirage Andreev Spectra Generated by Mesoscopic Leads in Nanowire Quantum Dots.
AB  - We study transport mediated by Andreev bound states formed in InSb nanowire
      quantum dots. Two kinds of superconducting source and drain contacts are used:
      epitaxial Al/InSb devices exhibit a doubling of tunneling resonances, while, in
      NbTiN/InSb devices, Andreev spectra of the dot appear to be replicated multiple
      times at increasing source-drain bias voltages. In both devices, a mirage of a
      crowded spectrum is created. To describe the observations a model is developed
      that combines the effects of a soft induced gap and of additional Andreev bound
      states both in the quantum dot and in the finite regions of the nanowire adjacent
      to the quantum dot. Understanding of Andreev spectroscopy is important for the
      correct interpretation of Majorana experiments done on the same structures.

PMID- 30296126
TI  - Comment on "Replica Symmetry Breaking in Trajectories of a Driven Brownian
      Particle".

PMID- 30296127
TI  - Ueda and Sasa Reply.

PMID- 30296128
TI  - Simultaneous Observation of a Topological Edge State and Exceptional Point in an
      Open and Non-Hermitian Acoustic System.
AB  - This Letter reports on the experimental observation of a topologically protected
      edge state and exceptional point in an open and non-Hermitian (lossy) acoustic
      system. Although the theoretical underpinning is generic to wave physics, the
      simulations and experiments are performed for an acoustic system. It has
      nontrivial topological properties that can be characterized by the Chern number
      provided that a synthetic dimension is introduced. Unidirectional reflectionless
      propagation, a hallmark of exceptional points, is unambiguously observed in both
      simulations and experiments.

PMID- 30296130
TI  - Energy Storage via Topological Spin Textures.
AB  - We formulate an energy-storage concept based on the free energy associated with
      metastable magnetic configurations. Despite the active magnetic region of the
      battery being electrically insulating, it can sustain effective hydrodynamics of
      spin textures, whose conservation law is governed by topology. To illustrate the
      key physics and potential functionality, we focus here on the simplest quasi-one
      dimensional case of planar winding of the magnetic order parameter. The energy is
      stored in the metastable winding number, which can be injected electrically by an
      appropriately tailored spin torque. Because of the nonvolatility and the
      endurance of magnetic systems, the injected energy can be stored essentially
      indefinitely, with the topological charge cycles that do not degrade over time.

PMID- 30296129
TI  - Binary Two-Dimensional Honeycomb Lattice with Strong Spin-Orbit Coupling and
      Electron-Hole Asymmetry.
AB  - Two-dimensional (2D) materials consisting of heavy atoms with particular
      arrangements may host exotic quantum properties. Here, we report a unique 2D
      semiconducting binary compound, a Sn_{2}Bi atomic layer on Si(111), in which
      hexagons are formed by bonding Bi with a triangular network of Sn. Because of the
      unique honeycomb configuration, the heavy elements, and the energy-dependent
      hybridization between Sn and Bi, 2D Sn_{2}Bi not only shows strong spin-orbit
      coupling effects but also exhibits high electron-hole asymmetry: Nearly free hole
      bands and dispersionless flat electron bands coexist in the same system. By
      tuning the Fermi level, it is possible to preserve both nearly free and strongly
      localized charge carriers in the same 2D material, which provides an ideal
      platform for the studies of strongly correlated phenomena and possible
      applications in nanodevices.

PMID- 30296131
TI  - Optimal Work Extraction and Thermodynamics of Quantum Measurements and
      Correlations.
AB  - We analyze the role of indirect quantum measurements in work extraction from
      quantum systems in nonequilibrium states. In particular, we focus on the work
      that can be obtained by exploiting the correlations shared between the system of
      interest and an additional ancilla, where measurement backaction introduces a
      nontrivial thermodynamic tradeoff. We present optimal state-dependent protocols
      for extracting work from both classical and quantum correlations, the latter
      being measured by discord. Our quantitative analysis establishes that, while the
      work content of classical correlations can be fully extracted by performing local
      operations on the system of interest, accessing work related to quantum discord
      requires a specific driving protocol that includes interaction between system and
      ancilla.

PMID- 30296132
TI  - Strongly Coupled Anisotropic Gauge Theories and Holography.
AB  - We initiate a nonperturbative study of anisotropic, nonconformal, and confining
      gauge theories that are holographically realized in gravity by generic Einstein
      axion-dilaton systems. In the vacuum, our solutions describe renormalization
      group flows from a conformal field theory in the UV to generic scaling solutions
      in the IR with generic hyperscaling violation and dynamical exponents theta and
      z. We formulate a generalization of the holographic c theorem to the anisotropic
      case. At finite temperature, we discover that the anisotropic deformation reduces
      the confinement-deconfinement phase transition temperature suggesting a possible
      alternative explanation of inverse magnetic catalysis solely based on anisotropy.
      We also study transport and diffusion properties in anisotropic theories and
      observe, in particular, that the butterfly velocity that characterizes both
      diffusion and growth of chaos transverse to the anisotropic direction saturates a
      constant value in the IR which can exceed the bound given by the conformal value.

PMID- 30296136
TI  - Role of Radial Charges on the Angular Momentum of Electromagnetic Fields: Spin
      3/2 Light.
AB  - Electromagnetic fields carry a linear and an angular momentum, the first being
      responsible for the existence of the radiation pressure and the second for the
      transfer of torque from electromagnetic radiation to matter. The angular momentum
      is considered to have two components, one due to the polarization state of the
      field, usually called spin angular momentum (SAM), and one due to the existence
      of topological azimuthal charges in the field phase profile, which leads to the
      orbital angular momentum (OAM). These two contributions to the total angular
      momentum of an electromagnetic field appear, however, to not be independent of
      each other, something which is described as spin-orbit coupling. Understanding
      the physics of this coupling has kept scientists busy for decades. Very recently
      it has been shown that electromagnetic fields necessarily carry also invariant
      radial charges that, as discussed in this Letter, play a key role in the angular
      momentum. Here we show that the total angular momentum consists in fact of three
      components: one component only dependent on the spin of the field, another
      dependent on the azimuthal charges carried by the field, and a third component
      dependent on the spin and the radial charges contained in the field. By properly
      controlling the number and coupling among these radial charges it is possible to
      design electromagnetic fields with a desired total angular momentum. Remarkably,
      we also discover fields with no orbital angular momentum and a spin angular
      momentum typical of spin-3/2 objects, irrespective of the fact that photons are
      spin-1 particles.

PMID- 30296134
TI  - Transition from Asynchronous to Oscillatory Dynamics in Balanced Spiking Networks
      with Instantaneous Synapses.
AB  - We report a transition from asynchronous to oscillatory behavior in balanced
      inhibitory networks for class I and II neurons with instantaneous synapses.
      Collective oscillations emerge for sufficiently connected networks. Their origin
      is understood in terms of a recently developed mean-field model, whose stable
      solution is a focus. Microscopic irregular firings, due to balance, trigger
      sustained oscillations by exciting the relaxation dynamics towards the
      macroscopic focus. The same mechanism induces in balanced excitatory-inhibitory
      networks quasiperiodic collective oscillations.

PMID- 30296137
TI  - Roura Replies.

PMID- 30296135
TI  - Nonreciprocity Realized with Quantum Nonlinearity.
AB  - Nonreciprocal devices are a key element for signal routing and noise isolation.
      Rapid development of quantum technologies has boosted the demand for a new
      generation of miniaturized and low-loss nonreciprocal components. Here, we use a
      pair of tunable superconducting artificial atoms in a 1D waveguide to
      experimentally realize a minimal passive nonreciprocal device. Taking advantage
      of the quantum nonlinear behavior of artificial atoms, we achieve nonreciprocal
      transmission through the waveguide in a wide range of powers. Our results are
      consistent with theoretical modeling showing that nonreciprocity is associated
      with the population of the two-qubit nonlocal entangled quasidark state, which
      responds asymmetrically to incident fields from opposing directions. Our
      experiment highlights the role of quantum correlations in enabling nonreciprocal
      behavior and opens a path to building passive quantum nonreciprocal devices
      without magnetic fields.

PMID- 30296138
TI  - Comment on "Circumventing Heisenberg's Uncertainty Principle in Atom
      Interferometry Tests of the Equivalence Principle".

PMID- 30296139
TI  - Unconventional Multiband Superconductivity in Bulk SrTiO_{3} and
      LaAlO_{3}/SrTiO_{3} Interfaces.
AB  - Although discovered many decades ago, superconductivity in doped SrTiO_{3}
      remains a topic of intense research. Recent experiments revealed that, upon
      increasing the carrier concentration, multiple bands cross the Fermi level,
      signaling the onset of Lifshitz transitions. Interestingly, T_{c} was observed to
      be suppressed across the Lifshitz transition of oxygen-deficient SrTiO_{3}; a
      similar behavior was also observed in gated LaAlO_{3}/SrTiO_{3} interfaces. Such
      a behavior is difficult to explain in the clean theory of two-band
      superconductivity, as the additional electronic states provided by the second
      band should enhance T_{c}. Here, we show that this unexpected behavior can be
      explained by the strong pair-breaking effect promoted by disorder, which takes
      place if the interband pairing interaction is subleading and repulsive. A
      consequence of this scenario is that, upon moving away from the Lifshitz
      transition, the two-band superconducting state changes from opposite-sign gaps to
      same-sign gaps.

PMID- 30296140
TI  - Erratum: Tests of General Relativity with GW150914 [Phys. Rev. Lett. 116, 221101
      (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.116.221101.

PMID- 30296141
TI  - Fragile Topology and Wannier Obstructions.
AB  - Topological phases, such as Chern insulators, are defined in terms of additive
      indices that are stable against the addition of trivial degrees of freedom. Such
      topology presents an obstruction to any Wannier representation, namely, the
      representation of the electronic states in terms of symmetric, exponentially
      localized Wannier functions. Here, we address the converse question: Do
      obstructions to Wannier representation imply stable band topology? We answer this
      in the negative, pointing out that some bands can also display a distinct type of
      "fragile topology." Bands with fragile topology do not admit any Wannier
      representation by themselves, but such a representation becomes possible once
      certain additional trivial degrees of freedom are supplied. We construct a
      physical model of fragile topology on the honeycomb lattice that also helps
      resolve a recent puzzle in band theory. This model provides a counterexample to
      the assumption that splitting of an "elementary band representation" introduced
      in [B. Bradlyn et al., Topological quantum chemistry, Nature (London) 547, 298
      (2017)] leads to bands that are individually topological. Instead, half of the
      split bands of our model realize a trivial band with exponentially localized
      symmetric Wannier functions, whereas the second half possess fragile topology.
      Our work highlights an important and previously overlooked connection between
      band structure and Wannier functions, and is expected to have far-reaching
      consequences given the central role played by Wannier functions in the modeling
      of real materials.

PMID- 30296142
TI  - Periodic Motion of Sedimenting Flexible Knots.
AB  - We study the dynamics of knotted deformable closed chains sedimenting in a
      viscous fluid. We show experimentally that trefoil and other torus knots often
      attain a remarkably regular horizontal toroidal structure while sedimenting, with
      a number of intertwined loops, oscillating periodically around each other. We
      then recover this motion numerically and find out that it is accompanied by a
      very slow rotation around the vertical symmetry axis. We analyze the dependence
      of the characteristic timescales on the chain flexibility and aspect ratio. It is
      observed in the experiments that this oscillating mode of the dynamics can
      spontaneously form even when starting from a qualitatively different initial
      configuration. In numerical simulations, the oscillating modes are usually
      present as transients or final stages of the evolution, depending on chain aspect
      ratio and flexibility, and the number of loops.

PMID- 30296143
TI  - High-Fidelity Control and Entanglement of Rydberg-Atom Qubits.
AB  - Individual neutral atoms excited to Rydberg states are a promising platform for
      quantum simulation and quantum information processing. However, experimental
      progress to date has been limited by short coherence times and relatively low
      gate fidelities associated with such Rydberg excitations. We report progress
      towards high-fidelity quantum control of Rydberg-atom qubits. Enabled by a
      reduction in laser phase noise, our approach yields a significant improvement in
      coherence properties of individual qubits. We further show that this high
      fidelity control extends to the multi-particle case by preparing a two-atom
      entangled state with a fidelity exceeding 0.97(3), and extending its lifetime
      with a two-atom dynamical decoupling protocol. These advances open up new
      prospects for scalable quantum simulation and quantum computation with neutral
      atoms.

PMID- 30296144
TI  - Strong and Tunable Spin-Lifetime Anisotropy in Dual-Gated Bilayer Graphene.
AB  - We report the discovery of a strong and tunable spin-lifetime anisotropy with
      excellent out-of-plane spin lifetimes up to 7.8 ns at 100 K in dual-gated bilayer
      graphene. Remarkably, this realizes the manipulation of spins in graphene by
      electrically controlled spin-orbit fields, which is unexpected due to graphene's
      weak intrinsic spin-orbit coupling (~12  MUeV). We utilize both the in-plane
      magnetic field Hanle precession and oblique Hanle precession measurements to
      directly compare the lifetimes of out-of-plane vs in-plane spins. We find that
      near the charge neutrality point, the application of a perpendicular electric
      field opens a band gap and generates an out-of-plane spin-orbit field that
      stabilizes out-of-plane spins against spin relaxation, leading to a large spin
      lifetime anisotropy (defined as the ratio between out-of-plane and in-plane spin
      lifetime) up to ~12 at 100 K. This intriguing behavior occurs because of the
      unique spin-valley coupled band structure of bilayer graphene. Our results
      demonstrate the potential for highly tunable spintronic devices based on dual
      gated 2D materials.

PMID- 30296145
TI  - Interaction-Driven Giant Orbital Magnetic Moments in Carbon Nanotubes.
AB  - Carbon nanotubes continue to be model systems for studies of confinement and
      interactions. This is particularly true in the case of so-called "ultraclean"
      carbon nanotube devices offering the study of quantum dots with extremely low
      disorder. The quality of such systems, however, has increasingly revealed glaring
      discrepancies between experiment and theory. Here, we address the outstanding
      anomaly of exceptionally large orbital magnetic moments in carbon nanotube
      quantum dots. We perform low temperature magnetotransport measurements of the
      orbital magnetic moment and find it is up to 7 times larger than expected from
      the conventional semiclassical model. Moreover, the magnitude of the magnetic
      moment monotonically drops with the addition of each electron to the quantum dot
      directly contradicting the widely accepted shell filling picture of single
      particle levels. We carry out quasiparticle calculations, both from first
      principles and within the effective-mass approximation, and find the giant
      magnetic moments can only be captured by considering a self-energy correction to
      the electronic band structure due to electron-electron interactions.

PMID- 30296147
TI  - Observation of Spin-Valley-Coupling-Induced Large Spin-Lifetime Anisotropy in
      Bilayer Graphene.
AB  - We report the first observation of a large spin-lifetime anisotropy in bilayer
      graphene (BLG) fully encapsulated between hexagonal boron nitride. We
      characterize the out-of-plane (tau_{?}) and in-plane (tau_{?}) spin lifetimes by
      oblique Hanle spin precession. At 75 K and the charge neutrality point (CNP), we
      observe a strong anisotropy of tau_{?}/tau_{?}=8+/-2. This value is comparable to
      graphene-transition-metal-dichalcogenide heterostructures, whereas our high
      quality BLG provides with tau_{?} up to 9 ns, a spin lifetime more than 2 orders
      of magnitude larger. The anisotropy decreases to 3.5+/-1 at a carrier density of
      n=6*10^{11}  cm^{-2}. Temperature-dependent measurements show above 75 K a
      decrease of tau_{?}/tau_{?} with increasing temperature, reaching the isotropic
      case close to room temperature. We explain our findings with electric-field
      induced spin-valley coupling arising from the small intrinsic spin-orbit fields
      in BLG of 12  MUeV at the CNP.

PMID- 30296146
TI  - Continuum Charge Excitations in High-Valence Transition-Metal Oxides Revealed by
      Resonant Inelastic X-Ray Scattering.
AB  - We present a theoretical investigation of the origin of Raman-like and
      fluorescencelike (FL) features of resonant inelastic x-ray scattering (RIXS)
      spectra. Using a combination of local-density approximation+dynamical mean-field
      theory and a configuration interaction solver for Anderson impurity model, we
      calculate the L-edge RIXS and x-ray absorption spectra of high-valence transition
      metal oxides LaCuO_{3} and NaCuO_{2}. We analyze in detail the behavior of the FL
      feature and show how it is connected to the details of electronic and crystal
      structure. On the studied compounds we demonstrate how material details determine
      whether the electron-hole continuum can be excited in the L-edge RIXS process.

PMID- 30296148
TI  - Tuning Anti-Klein to Klein Tunneling in Bilayer Graphene.
AB  - We show that in gapped bilayer graphene, quasiparticle tunneling and the
      corresponding Berry phase can be controlled such that they exhibit features of
      single-layer graphene such as Klein tunneling. The Berry phase is detected by a
      high-quality Fabry-Perot interferometer based on bilayer graphene. By raising the
      Fermi energy of the charge carriers, we find that the Berry phase can be
      continuously tuned from 2pi down to 0.68pi in gapped bilayer graphene, in
      contrast to the constant Berry phase of 2pi in pristine bilayer graphene.
      Particularly, we observe a Berry phase of pi, the standard value for single-layer
      graphene. As the Berry phase decreases, the corresponding transmission
      probability of charge carriers at normal incidence clearly demonstrates a
      transition from anti-Klein tunneling to nearly perfect Klein tunneling.

PMID- 30296150
TI  - Anomalous Breaking of Scale Invariance in a Two-Dimensional Fermi Gas.
AB  - The frequency of the breathing mode of a two-dimensional Fermi gas with zero
      range interactions in a harmonic confinement is fixed by the scale invariance of
      the Hamiltonian. Scale invariance is broken in the quantized theory by
      introducing the two-dimensional scattering length as a regulator. This is an
      example of a quantum anomaly in the field of ultracold atoms and leads to a shift
      of the frequency of the collective breathing mode of the cloud. In this work, we
      study this anomalous frequency shift for a two-component Fermi gas in the
      strongly interacting regime. We measure significant upwards shifts away from the
      scale-invariant result that show a strong interaction dependence. This
      observation implies that scale invariance is broken anomalously in the strongly
      interacting two-dimensional Fermi gas.

PMID- 30296149
TI  - Quantum Anomaly and 2D-3D Crossover in Strongly Interacting Fermi Gases.
AB  - We present an experimental investigation of collective oscillations in
      harmonically trapped Fermi gases through the crossover from two to three
      dimensions. Specifically, we measure the frequency of the radial monopole
      oscillation or breathing mode in highly oblate gases with tunable interactions.
      The breathing mode frequency is set by the adiabatic compressibility and probes
      the thermodynamic equation of state. In 2D, a dynamical scaling symmetry for
      atoms interacting via a delta potential predicts the breathing mode to occur at
      exactly twice the harmonic confinement frequency. However, a renormalized quantum
      treatment introduces a new length scale which breaks this classical scale
      invariance resulting in a so-called quantum anomaly. Our measurements deep in the
      2D regime lie above the scale-invariant prediction for a range of interaction
      strengths providing evidence for the quantum anomaly and signifying the breakdown
      of an elementary delta-potential model of atomic interactions. By varying the
      atom number we can tune the chemical potential and see the breathing mode
      frequency evolve smoothly between the 2D to 3D thermodynamic limits.

PMID- 30296151
TI  - Deterministic Free-Space Source of Single Photons Using Rydberg Atoms.
AB  - We propose an efficient free-space scheme to create single photons in a well
      defined spatiotemporal mode. To that end, we first prepare a single source atom
      in an excited Rydberg state. The source atom interacts with a large ensemble of
      ground-state atoms via a laser-mediated dipole-dipole exchange interaction. Using
      an adiabatic passage with a chirped laser pulse, we produce a spatially extended
      spin wave of a single Rydberg excitation in the ensemble, accompanied by the
      transition of the source atom to another Rydberg state. The collective atomic
      excitation can then be converted to a propagating optical photon via a coherent
      coupling field. In contrast to previous approaches, our single-photon source does
      not rely on the strong coupling of a single emitter to a resonant cavity, nor
      does it require the heralding of collective excitation or complete Rydberg
      blockade of multiple excitations in the atomic ensemble.

PMID- 30296152
TI  - Keldysh-Rutherford Model for the Attoclock.
AB  - We demonstrate a clear similarity between attoclock offset angles and Rutherford
      scattering angles taking the Keldysh tunneling width as the impact parameter and
      the vector potential of the driving pulse as the asymptotic velocity. This simple
      model is tested against the solution of the time-dependent Schrodinger equation
      using hydrogenic and screened (Yukawa) potentials of equal binding energy. We
      observe a smooth transition from a hydrogenic to "hard-zero" intensity dependence
      of the offset angle with variation of the Yukawa screening parameter.
      Additionally, we make a comparison with the attoclock offset angles for various
      noble gases obtained with the classical-trajectory Monte Carlo method. In all
      cases we find a close correspondence between the model predictions and numerical
      calculations. This suggests a largely Coulombic origin of the attoclock offset
      angle and casts further doubt on its interpretation in terms of a finite
      tunneling time.

PMID- 30296153
TI  - Microscopic Origin of Frictional Rheology in Dense Suspensions: Correlations in
      Force Space.
AB  - We develop a statistical framework for the rheology of dense, non-Brownian
      suspensions, based on correlations in a space representing forces, which is dual
      to position space. Working with the ensemble of steady state configurations
      obtained from simulations of suspensions in two dimensions, we find that the
      anisotropy of the pair correlation function in force space changes with confining
      shear stress (sigma_{xy}) and packing fraction (phi). Using these microscopic
      correlations, we build a statistical theory for the macroscopic friction
      coefficient: the anisotropy of the stress tensor, MU=sigma_{xy}/P. We find that
      MU decreases (i) as phi is increased and (ii) as sigma_{xy} is increased. Using a
      new constitutive relation between MU and viscosity for dense suspensions that
      generalizes the rate-independent one, we show that our theory predicts a
      discontinuous shear thickening flow diagram that is in good agreement with
      numerical simulations, and the qualitative features of MU that lead to the
      generic flow diagram of a discontinuous shear thickening fluid observed in
      experiments.

PMID- 30296154
TI  - Constraint-Based Approach to Granular Dispersion Rheology.
AB  - We present a phenomenological model for granular suspension rheology in which
      particle interactions enter as constraints to relative particle motion. By
      considering constraints that are formed and released by stress respectively, we
      derive a range of experimental flow curves in a single treatment and predict
      singularities in viscosity and yield stress consistent with literature data.
      Fundamentally, we offer a generic description of suspension flow that is
      independent of bespoke microphysics.

PMID- 30296155
TI  - Anomalous Hall Effect in 2D Dirac Materials.
AB  - We present a unified theory of charge carrier transport in 2D Dirac systems with
      broken mirror inversion and time-reversal symmetries (e.g., as realized in
      ferromagnetic graphene). We find that the entanglement between spin and
      pseudospin SU(2) degrees of freedom stemming from spin-orbit effects leads to a
      distinctive gate voltage dependence (change of sign) of the anomalous Hall
      conductivity approaching the topological gap, which remains robust against
      impurity scattering and thus is a smoking gun for magnetized 2D Dirac fermions.
      Furthermore, we unveil a robust skew scattering mechanism, modulated by the spin
      texture of the energy bands, which causes a net spin accumulation at the sample
      boundaries even for spin-transparent disorder. The newly unveiled extrinsic spin
      Hall effect is readily tunable by a gate voltage and opens novel opportunities
      for the control of spin currents in 2D ferromagnetic materials.

PMID- 30296156
TI  - Quantum Spin Hall Effect and Spin Bott Index in a Quasicrystal Lattice.
AB  - Despite the rapid progress in the field of the quantum spin Hall (QSH) effect,
      most of the QSH systems studied up to now are based on crystalline materials.
      Here we propose that the QSH effect can be realized in quasicrystal lattices
      (QLs). We show that the electronic topology of aperiodic and amorphous insulators
      can be characterized by a spin Bott index B_{s}. The nontrivial QSH state in a QL
      is identified by a nonzero spin Bott index B_{s}=1, associated with robust edge
      states and quantized conductance. We also map out a topological phase diagram in
      which the QSH state lies in between a normal insulator and a weak metal phase due
      to the unique wave functions of QLs. Our findings not only provide a better
      understanding of electronic properties of quasicrystals but also extend the
      search of the QSH phase to aperiodic and amorphous materials that are
      experimentally feasible.

PMID- 30296158
TI  - Painting Nonclassical States of Spin or Motion with Shaped Single Photons.
AB  - We propose a robust scheme for generating macroscopic superposition states of
      spin or motion with the aid of a single photon. Shaping the wave packet of the
      photon enables high-fidelity preparation of nonclassical states of matter even in
      the presence of photon loss. Success is heralded by photodetection, enabling the
      scheme to be implemented with a weak coherent field. We analyze applications to
      preparing Schrodinger cat states of a collective atomic spin or of a mechanical
      oscillator coupled to an optical resonator. The method generalizes to preparing
      arbitrary superpositions of coherent states, enabling full quantum control. We
      illustrate this versatility by showing how to prepare Dicke or Fock states, as
      well as superpositions in the Dicke or Fock basis.

PMID- 30296157
TI  - Spectral Evidence for Emergent Order in Ba_{1-x}Na_{x}Fe_{2}As_{2}.
AB  - We report an angle-resolved photoemission spectroscopy study of the iron-based
      superconductor family, Ba_{1-x}Na_{x}Fe_{2}As_{2}. This system harbors the
      recently discovered double-Q magnetic order appearing in a reentrant C_{4} phase
      deep within the underdoped regime of the phase diagram that is otherwise
      dominated by the coupled nematic phase and collinear antiferromagnetic order.
      From a detailed temperature-dependence study, we identify the electronic response
      to the nematic phase in an orbital-dependent band shift that strictly follows the
      rotational symmetry of the lattice and disappears when the system restores C_{4}
      symmetry in the low temperature phase. In addition, we report the observation of
      a distinct electronic reconstruction that cannot be explained by the known
      electronic orders in the system.

PMID- 30296160
TI  - Discontinuous Phase Transitions in Nonlocal Schloegl Models for Autocatalysis:
      Loss and Reemergence of a Nonequilibrium Gibbs Phase Rule.
AB  - We consider Schloegl models (or contact processes) where particles on a square
      grid annihilate at a rate p and are created at a rate of k_{n}=n(n-1)/[N(N-1)] at
      empty sites with n particles in a neighborhood Omega_{N} of size N. Simulation
      reveals a discontinuous transition between populated and vacuum states, but
      equistable p=p_{eq} determined by the stationarity of planar interfaces between
      these states depends on the interface orientation and on Omega_{N}. The behavior
      for large Omega_{N} follows from continuum equations. These also depend on the
      interface orientation and on Omega_{N} shape, but a unique p_{eq}=0.211 376 320 4
      emerges imposing a Gibbs phase rule.

PMID- 30296159
TI  - Pareto Optimality in Multilayer Network Growth.
AB  - We model the formation of multilayer transportation networks as a multiobjective
      optimization process, where service providers compete for passengers, and the
      creation of routes is determined by a multiobjective cost function encoding a
      trade-off between efficiency and competition. The resulting model reproduces well
      real-world systems as diverse as airplane, train, and bus networks, thus
      suggesting that such systems are indeed compatible with the proposed local
      optimization mechanisms. In the specific case of airline transportation systems,
      we show that the networks of routes operated by each company are placed very
      close to the theoretical Pareto front in the efficiency-competition plane, and
      that most of the largest carriers of a continent belong to the corresponding
      Pareto front. Our results shed light on the fundamental role played by
      multiobjective optimization principles in shaping the structure of large-scale
      multilayer transportation systems, and provide novel insights to service
      providers on the strategies for the smart selection of novel routes.

PMID- 30296161
TI  - Fractional Excitonic Insulator.
AB  - We argue that a correlated fluid of electrons and holes can exhibit a fractional
      quantum Hall effect at zero magnetic field analogous to the Laughlin state at
      filling 1/m. We introduce a variant of the Laughlin wave function for electrons
      and holes and show that for m=1 it is the exact ground state of a free fermion
      model that describes p_{x}+ip_{y} excitonic pairing. For m>1 we develop a simple
      composite fermion mean field theory, and we present evidence that our wave
      function correctly describes this phase. We derive an interacting Hamiltonian for
      which our wave function is the exact ground state, and we present physical
      arguments that the m=3 state can be realized in a system in which energy bands
      with angular momentum that differ by 3 cross at the Fermi energy. This leads to a
      gapless state with (p_{x}+ip_{y})^{3} excitonic pairing, which we argue is
      conducive to forming the fractional excitonic insulator in the presence of
      interactions. Prospects for numerics on model systems and band structure
      engineering to realize this phase in real materials are discussed.

PMID- 30296162
TI  - Network Model of the Disordered Phase in Symmetric Diblock Copolymer Melts.
AB  - We present a model for the order-disorder transition of symmetric A-B diblock
      copolymer melts in which the disordered phase is treated as a bicontinuous
      network, and in which self-consistent field predictions of properties of an
      analogous ordered network are used to estimate some properties. Such a model is
      shown to accurately predict the latent heat of this transition. The dependence of
      the location of the transition upon the invariant degree of polymerization N[over
      -] is shown to be consistent with a simple hypothesis that the disordered
      bicontinuous structure is stabilized relative to an analogous ordered network by
      a nearly constant entropy per network junction.

PMID- 30296163
TI  - Dual Conformal Structure Beyond the Planar Limit.
AB  - The planar scattering amplitudes of N=4 super-Yang-Mills theory display
      symmetries and structures which underlie their relatively simple analytic
      properties such as having only logarithmic singularities and no poles at
      infinity. Recent work shows in various nontrivial examples that the simple
      analytic properties of the planar sector survive into the nonplanar sector, but
      this has yet to be understood from underlying symmetries. Here, we explicitly
      show that for an infinite class of nonplanar integrals that covers all subleading
      color contributions to the two-loop four- and five-point amplitudes of N=4 super
      Yang-Mills theory, symmetries analogous to dual conformal invariance exist. A
      natural conjecture is that this continues to all amplitudes of the theory at any
      loop order.

PMID- 30296164
TI  - Effects of Polarization on Particle-Laden Flows.
AB  - Simulations of particle-laden flow with dielectric particles are carried out with
      varying levels of electrical charging and particle polarization. Simulation
      results reveal three distinct flow regions. For low particle charge and
      polarizability, flow is nearly symmetric and nonmeandering. For strong charging
      and polarization, particles form a continuous and tightly clustered sheet close
      to one of the walls. Between these extremes, particles form localized particle
      rich regions, around which the gas executes a meandering flow. These results
      indicate that polarization can lead to qualitative changes in the characteristics
      of particle-laden flows subject to tribocharging.

PMID- 30296165
TI  - Hyperbolic Dispersion Arising from Anisotropic Excitons in Two-Dimensional
      Perovskites.
AB  - Excitations of free electrons and optical phonons are known to permit access to
      the negative real part of relative permittivities (epsilon^{'}<0) that yield
      strong light-matter interactions. However, negative epsilon^{'} arising from
      excitons has been much less explored. Via development of a dielectric-coating
      based technique described herein, we report fundamental optical properties of two
      dimensional hybrid perovskites (2DHPs), composed of alternating layers of
      inorganic and organic sublattices. Low members of 2DHPs (N=1 and N=2) exhibit
      negative epsilon^{'} stemming from the large exciton binding energy and sizable
      oscillator strength. Furthermore, hyperbolic dispersion (i.e., epsilon^{'}
      changes sign with directions) occurs in the visible range, which has been
      previously achieved only with artificial metamaterials. Such naturally occurring,
      exotic dispersion stems from the extremely anisotropic excitonic behaviors of
      2DHPs, and can intrinsically support a large photonic density of states. We
      suggest that several other van der Waals solids may exhibit similar behaviors
      arising from excitonic response.

PMID- 30296166
TI  - Molecular techniques reveal more secrets of fermented foods.
AB  - Fermented foods were likely to have been the first among all types of processed
      foods consumed by human beings. The role that fermented food plays is not only
      related to the development of civilizations and cultural relationships between
      countries but also related to the nutritional importance of its population. Of
      course, the early manufacturers of fermented foods didn't take into account the
      advantages of modern sciences, because enzymes and microorganisms were discovered
      just 150-200 years ago. For that reason, we can conclude why the ancient
      fermentation techniques were known to philosophers and alchemists, but not to
      biologists. It demonstrated that the fermentation mechanisms involved many
      secrets still undiscovered. Recently, applications of molecular techniques for
      analyzing and study the fermented foods have been explored. In this review, we
      provide answers with a critical vision to many questions for understanding the
      role of molecular techniques to discover the secrets of fermented foods such as
      how to evaluate the traditional fermented foods? Why using molecular techniques
      to study the fermented foods not else? Is the future will carry to us a boom in
      molecular technologies contribute to the detection of more secrets of the
      fermented food?

PMID- 30296167
TI  - Changes of ruminal pH, rumination activity and feeding behaviour during early
      lactation as affected by different energy and fibre concentrations of roughage in
      pluriparous dairy cows.
AB  - The aim of this study was to assess differences of ruminal pH and rumination
      activity between the prepartal and postpartal period of cows and to investigate
      changes of feeding behaviour and ruminal fermentation depending on postpartal
      rations with slight differences in roughage energy and fibre concentration.
      Therefore, 11 rumen-cannulated German Holstein cows were used from 3 weeks
      antepartum until 16 weeks postpartum. During the dry period, all cows received
      the same diet. After calving cows were assigned to two groups receiving partial
      mixed rations with different energy concentrations (6.1 MJ NEL/kg DM [moderate],
      with 18% straw on dry matter [DM] basis, group MR) or 6.5 MJ NEL/kg DM [high],
      with 6% straw on DM basis, group HR). In both groups, concentrates were supplied
      on average at 45% of total DM intake. Circadian measurements of ruminal pH,
      ruminal temperature and rumination activity were conducted weekly during the
      transition period and bi-weekly after week 4 postpartum. Throughout the
      postpartal period, feed intake behaviour was measured, and twice during the
      experiment, rumen fluid composition and net-acid-base excretion in urine were
      determined. Mean ruminal pH, feeding behaviour, rumination activity and rumen
      fluid composition did not differ between the groups, whereas group HR exhibited
      higher diurnal variations of pH and had a lower rumen temperature than group MR
      postpartum. However, these differences also occurred during the prepartal period
      when groups received equal rations. It was observed that ruminal pH values and
      the risk for subacute ruminal acidosis (SARA) were increased during postpartal
      period, whereby the circadian pH values showed high cow-individual variations.
      Overall, differences of energy and fibre concentrations in roughage did not
      affect the observed variables, whereby it should be noted that the number of cows
      was quite low in this study. Our results suggest that the ruminal pH
      characteristics are rather cow individual, indicating that cows presumably differ
      in their susceptibility to develop SARA.

PMID- 30296168
TI  - The temporal pattern of recovery in eccentric hamstring strength post-soccer
      specific fatigue.
AB  - Eccentric hamstring strength is an aetiological risk factor for soccer injury.
      The temporal pattern of recovery post-exercise is critical in injury management.
      18 male professional soccer players completed baseline assessments of eccentric
      hamstring strength at isokinetic speeds of 60, 150 and 300 degrees . s-1. Post
      SAFT90 measures were repeated immediately, + 24 hrs, + 48 hrs and + 72 hrs. Main
      effects for recovery time and testing speed in average torque (AvT), peak torque
      (PT) and the corresponding angle (O) were supplemented by regression modelling to
      describe the temporal pattern of recovery. A main effect for isokinetic testing
      speed was observed in PT and AvT. A main effect for recovery time highlighted
      greater strength pre-exercise, with a quadratic pattern to temporal recovery
      highlighting minima achieved at between 40-48 hrs. Strength parameters are not
      fully recovered until 96 hrs post soccer specific fatigue, with implications for
      training design and injury management, particularly within fixture-congested
      periods.

PMID- 30296169
TI  - Stress reappraisal during a mathematics competition: testing effects on
      cardiovascular approach-oriented states and exploring the moderating role of
      gender.
AB  - BACKGROUND AND OBJECTIVES: Effects of reappraising stress arousal during an
      interpersonal competition were tested on physiological functioning and
      performance. Additionally, the moderating role of gender was explored. DESIGN AND
      METHOD: Participants (N = 279) were randomly assigned to a stress reappraisal,
      stress-is-debilitating, or a neutral control condition. Reappraisal materials
      educated participants about the adaptive benefits of stress, whereas stress-is
      debilitating materials instructed participants to avoid stress. Control materials
      did not mention stress. Participants then competed against a gender-matched
      confederate on a 10-minute math performance task while cardiovascular reactivity
      was assessed. Participants were instructed to complete math problems as quickly
      and accurately as they could and were informed that a winner and loser would be
      determined by the resulting math scores. RESULTS: Reappraising stress arousal led
      to more adaptive challenge-like cardiovascular responses, but no condition
      effects were observed on math performance. Exploratory analyses revealed that
      reappraisal instructions were effective for improving physiological functioning
      and facilitating performance for men, but women were unaffected by the
      manipulation. CONCLUSIONS: Reappraising stress arousal can improve physiological
      functioning during interpersonal competitions, but effects may be limited to men.
      Implications for future research are discussed.

PMID- 30296170
TI  - Spectral Ties: Hospital Hauntings Across the Line of Control.
AB  - In this article, we trace encounters between humans and phantasmic entities in
      hospitals in Indian-occupied and Pakistan-controlled Kashmir. In Pakistan, the
      presence of spectral beings (jinni) in hospitals is linked to state and sectarian
      violence, which precipitates ruptures between jinni and human worlds. Such
      breaches permit jinni to manifest in the medical present, where insecure actors
      harness them to ventriloquize unspoken anxieties. In Indian-occupied Kashmir,
      jinn-like, chronically mentally ill patients haunt psychiatric modernization
      projects. In embracing a jinneaological approach to medical crises, we theorize
      hospitals as multi-temporal and multi-dimensional spaces called "tesseracts," in
      which human-nonhuman encounters serve existential and political purposes.

PMID- 30296172
TI  - The use of estradiol metered-dose transdermal spray in clinical practice.
AB  - OBJECTIVE: The aim of this study was to evaluate the use of novel estradiol
      metered-dose transdermal spray (EMDTS) in the treatment of acute climacteric
      syndrome. METHODS: A multicenter open-label trial was conducted with a 24-week
      intervention. EMDTS 1.53 mg was given to symptomatic menopausal women. The
      Menopause Rating Scale (MRS) was used to assess the climacteric syndrome
      severity. The Friedman non-parametric test and a post-hoc test with Bonferroni
      correction were used for statistical evaluation. RESULTS: A total of 132 women
      were enrolled in 20 centers, of whom 123 (93.2%) completed the study. The average
      age of patients was 53.8 years (37-65 years). The study was discontinued by 6.8%
      of women. The patients were checked at the beginning of the study, and after 12
      and 24 weeks. There was a statistically significant drop (p < 0.001) in MRS
      values both after 12 and 24 weeks of therapy. The average MRS values improved by
      66.2% between the first and the third visits. The most significant improvement
      was manifested in patients with initial moderate climacteric syndrome (70.9%).
      CONCLUSION: This study confirms that application of EMDTS offers a novel
      treatment option for climacteric symptoms.

PMID- 30296173
TI  - Change in quality of life in relation to returning to work after acquired brain
      injury: a population-based register study.
AB  - PURPOSE: This study investigated changes in quality of life (QoL) in relation to
      return to work among patients with acquired brain injury (ABI). METHOD: The
      sample consisted of 1487 patients with ABI (63% men) aged 18-66 years (mean age
      52) from the WebRehab Sweden national quality register database. Only patients
      who worked at least 50% at admission to hospital and were on full sick leave at
      discharge from hospital were included. QoL was measured by the EuroQol EQ-5D
      questionnaire. RESULTS: Patients who returned to work perceived a larger
      improvement in QoL from discharge to follow-up one year after injury compared to
      patients who had not returned to work. This difference remained after adjustment
      for other factors associated with improved QoL, such as having a university
      education, increased Extended Glasgow Outcome Scale scores and getting one's
      driving licence reinstated. CONCLUSION: Return to work is an important factor for
      change in QoL among patients with ABI, even after adjusting for other factors
      related to QoL. This is consistent with the hypothesis that having employment is
      meaningful, increases self-esteem and fosters participation in society. Thus,
      helping patients with ABI return to work has a positive influence on QoL.

PMID- 30296174
TI  - Sit-Stand Desk Software Can Now Monitor and Prompt Office Workers to Change
      Health Behaviors.
AB  - OBJECTIVE: To determine the effectiveness of a computer-based intervention
      designed to increase sit-stand desk usage and help reverse workplace physical
      inactivity. BACKGROUND: Sit-stand desks have been successful in reducing
      workplace sedentary behavior, but the challenge remains for an effective method
      to increase the usage in order to experience the health and productivity
      benefits. METHOD: Data collection (1-year field study with 194 workers) used a
      novel method of computer software that continuously recorded objective electric
      sit-stand desk usage, while taking into account the time a worker spends away
      from their desk (breaks, meetings). During the baseline period, all workers' desk
      usage was recorded by the software, and the intervention period consisted of
      software reminders and real-time feedback to all workers to change desk
      positions. Pooled means were calculated to determine desk usage patterns, and
      effect sizes and pairwise mean differences were analyzed to test for intervention
      significance. RESULTS: The intervention doubled desk usage by increasing ~1
      change to ~2 changes per work day. There was a 76% reduction in workers who never
      used the sit-stand function of the desk. Medium to large effect sizes from the
      intervention were observed in all three primary outcome measures (desk in
      sitting/standing position and desk position changes per work day). CONCLUSION:
      These findings demonstrate an effective intervention that increased postural
      transitioning and interrupted prolonged inactivity while remaining at the
      workstation. APPLICATION: The methods and results in this research study show
      that we can quantify an increase in desk usage and collect aggregate data
      continuously.

PMID- 30296176
TI  - Chronic traumatic encephalopathy: what do parents of youth athletes know about
      it?
AB  - INTRODUCTION/BACKGROUND: Chronic Traumatic Encephalopathy (CTE) is a
      neurodegenerative disease thought to be caused by repeated head impacts and
      associated with deficits in cognition. Despite research and media attention,
      there is little science-based information available for the public. Also unclear
      is what the public and particularly parents of youth athletes know about CTE. The
      U.S. Centers for Disease Control and Prevention (CDC) surveyed parents of young
      athletes to fill this gap. METHODS: CDC analysed 12 CTE-related questions that
      appeared in Porter Novelli Public Service's 2017 SummerStyles opinion survey.
      Analyses focused on 674 parents of children who play in a youth sports programme.
      RESULTS: Half of parents had at least one child who plays contact sports. About
      one-third of respondents reported being somewhat or very familiar with CTE. Most
      parents (81.7%) have not received educational materials on CTE from a school or
      sports programme. Healthcare providers were the preferred source of information
      about CTE (70%), followed by sports coaches (54%). DISCUSSION/CONCLUSION: This
      analysis identified information needs related to CTE among parents of young
      athletes. These findings can be used by health educators to tailor educational
      materials to meet information needs. Educational materials that emphasize
      potential prevention strategies and symptom onset may be beneficial.

PMID- 30296175
TI  - Single clip: An improvement of the filament-perforation mouse subarachnoid
      haemorrhage model.
AB  - OBJECTIVE: The endovascular filament-perforation model turned out to become the
      most popular one for the reproduction of prominent pathophysiological features
      observed after human subarachnoid haemorrhage (SAH). However, few studies have
      considered methods that may minimize surgically induced injury. This study
      described an improved and simplified surgical procedure in which a single clip is
      placed at the external carotid artery (ECA). METHOD: Male C57BL/6 mice were given
      either a classic endovascular filament SAH model, improved endovascular filament
      SAH model or sham injury. Multiple strategies, including MRI with T2-weighted
      imaging and 18F-FDG PET/CT scanning, were performed to compare the improved and
      classic SAH models. RESULTS: The new method of filament model resulted a typical
      pathophysiological progress of early brain injury (EBI), including cerebral
      oedema, blood brain barrier (BBB) disruption, neuronal apoptosis and microglia
      activation. The improved SAH model is characterized by a shorter operation time
      (15.65 +/- 0.64 min vs. 21.75 +/- 0.94 min), reduced surgically induced injury
      (decreased 18F-FDG standardized uptake values (SUV): 1.7 +/- 0.07 vs. 2.02 +/-
      0.11), and stable cerebral perfusion before SAH. CONCLUSIONS: The improved
      surgical technique appears to be a feasible tool for experimental and
      translational studies of SAH.

PMID- 30296177
TI  - How does visual context influence recognition of facial emotion in people with
      traumatic brain injury?
AB  - OBJECTIVE: The current study assessed recognition of facial emotional stimuli
      following traumatic brain injury (TBI) and examined whether performance may be
      influenced by emotional visual scenes. METHODS: Thirty-five patients with
      moderate-to-severe TBI and 55 matched controls completed the novel Angers Facial
      Expression in Context Task (AFECT), designed to examine recognition of facial
      expressions of basic emotions in both congruent and incongruent emotional visual
      contexts. RESULTS: In comparison with non-brain damaged adults, patients with TBI
      performed more poorly and slowly on both contextual conditions (congruent vs.
      incongruent) of the AFECT. CONCLUSION: Taken together, these results raise the
      possibility that adults with TBI may not fully benefit from supportive contextual
      cues. Also, they stress the importance of using emotional stimuli that better
      capture affect processing in real-world contexts and open up new avenues to
      better understand negative social outcomes in patients with TBI.

PMID- 30296178
TI  - Emotion recognition depends on subjective emotional experience and not on facial
      expressivity: evidence from traumatic brain injury.
AB  - BACKGROUND: Recognizing how others feel is paramount to social situations and
      commonly disrupted following traumatic brain injury (TBI). This study tested
      whether problems identifying emotion in others following TBI is related to
      problems expressing or feeling emotion in oneself, as theoretical models place
      emotion perception in the context of accurate encoding and/or shared emotional
      experiences. METHODS: Individuals with TBI (n = 27; 20 males) and controls (n =
      28; 16 males) were tested on an emotion recognition task, and asked to adopt
      facial expressions and relay emotional memories according to the presentation of
      stimuli (word and photos). After each trial, participants were asked to self
      report their feelings of happiness, anger and sadness. Judges that were blind to
      the presentation of stimuli assessed emotional facial expressivity. RESULTS:
      Emotional experience was a unique predictor of affect recognition across all
      emotions while facial expressivity did not contribute to any of the regression
      models. Furthermore, difficulties in recognizing emotion for individuals with TBI
      were no longer evident after cognitive ability and experience of emotion were
      entered into the analyses. CONCLUSIONS: Emotion perceptual difficulties following
      TBI may stem from an inability to experience affective states and may tie in with
      alexythymia in clinical conditions.

PMID- 30296179
TI  - Identification of valid reference genes for circadian gene-expression studies in
      human mammary epithelial cells.
AB  - The circadian clock controls most of the physiological processes in the body
      throughout days and nights' alternation. Its dysregulation has a negative impact
      on many aspects of human health, such as obesity, lipid disorders, diabetes, skin
      regeneration, hematopoiesis and cancer. To date, poor is known on the molecular
      mechanisms that links mammary gland homeostasis to the circadian clock but recent
      reports highlight the importance of loss of circadian genes for mammary gland
      development and during tumour progression in breast cancer. Gene expression
      studies are then required to clarify how the circadian clock can modulates the
      human mammary gland development during ontology and its behaviour in
      physiological and oncogenic context. For this, in addition to genome-wide
      studies, real-time quantitative RT-PCR (qPCR) is a powerful and pertinent
      technique to quantify the expression of a reduced set of genes of interest in
      many different samples. Relative quantification of qPCR data requires the use of
      reference genes for normalisation. For circadian studies, reference genes
      expression must not oscillate in mirror of the circadian clock and must not be
      affected by the synchronisation protocols required in vitro to reset the
      circadian clock. Inappropriate selection of reference genes can consequently
      affect the amplitude of gene expression oscillation and bias data interpretation.
      Currently, no standard reference genes have been validated regarding these
      criteria for human mammary epithelial cells and the purpose of this study was to
      fill this gap. For this, we used the RefFinder tool, which combines four
      different algorithms, on 9 candidate reference genes. We compared reference genes
      stability using three different synchronisation protocols applied on four
      different mammary epithelial cell lines. This allowed us to define a set of
      reference genes in human mammary epithelial cells whose expression remains stable
      despite synchronisation protocols. We observed that the synchronisation of cells
      by serum shock was the most suitable procedure for maintaining the amplitude of
      oscillation of clock genes over time and we identified RPL4, RPLP0, HSPCB and TBP
      as an optimal combination of reference genes for the normalisation of the
      oscillatory expression of clock genes in human mammary epithelial cells.

PMID- 30296180
TI  - Employee control over scheduling of shifts and objectively measured working hour
      characteristics: a cross-sectional analysis of linked register and survey data.
AB  - We aimed to study the association of perceived control over scheduling of shifts
      with objectively measured working hour characteristics in shift workers. The
      participants were 5128 hospital employees (91% women, 85% nursing personnel,
      average age 43 years) in period-based work (114:45h/3 weeks) from the 2015
      Finnish Public Sector study. Survey responses to a measure of control over
      scheduling of shifts were linked to payroll data on working hour characteristics
      during the 91 days preceding the survey. We used multinomial logistic regression
      to assess differences in dichotomized proportion of working hour characteristics
      (being full-time worker, number of work shifts, long work weeks (>40h and
      >48h/week), long work shifts (>12-h), evening and night shifts, quick returns
      (<11h shift interval), single days off, weekend work, >4 consecutive work shifts,
      and variability of shift length with cut points at 10% or 25% between employees
      with high, intermediate, or low control over scheduling of shifts. Analyses were
      adjusted for age, sex, education, full-/part-time work (where applicable),
      duration of shift work experience, perceived work ability, children < 18 years in
      the household, and overall stressfulness of the life situation. Differences
      between age groups, men and women, and levels of work ability were examined using
      interaction terms. In adjusted analyses, the proportion of full-time workers was
      lower among employees with intermediate control over scheduling of shifts
      compared to those with high control (OR 0.78, 95% CI 0.61-0.98). High proportion
      (>25%) of weekend work was lower among employees with low control over scheduling
      of shifts compared to high control (OR 0.75, 95% CI 0.61-0.93). High proportion
      (>25%) of having >4 consecutive work shifts was associated with lower control
      over scheduling of shifts (OR 1.35, 95% CI 1.13-1.62). Variability of shift
      length was lower among employees with intermediate and low control over
      scheduling of shifts compared to those with high control (OR 0.78, 95% CI 0.66
      0.93; OR 0.62, 95% CI 0.51-0.75, respectively). No association was observed
      between the level of control over scheduling of shifts and high proportion of
      long work weeks (>25% of >40h weeks and >10% of >48h weeks), long work shifts
      (>25%), quick returns (>25%), single days off (>25%), and evening or night shifts
      (>10%) in the whole sample. In subgroup analyses, women with low control over
      scheduling shifts had lower odds ratio (OR 0.58, 95% CI 0.37-0.91) and men had
      higher odds ratio (OR 2.97, 95% CI 1.26-6.98) for large proportion of >12-h
      shifts. In conclusion, the employees with high control over scheduling of shifts
      had slightly more often unsocial working hour characteristics than those with
      intermediate or low control over scheduling of shifts. The findings, however,
      suggest that good work time control in shift work can be possible without
      compromising shift ergonomics.

PMID- 30296181
TI  - Circadian variations in the onset of aortic dissection in northern China.
AB  - This study explored the periodic changes in the onset of aortic dissection in a
      single center in northern China, with the goal to improve predictability and
      prevention. We collected the clinical data of 1121 patients from Hebei Province
      treated for acute aortic dissection at Fuwai Hospital between January 2010 and
      December 2016. The patterns of aortic dissection during different periods of each
      day, each month, and each quarter of a year were analyzed. Variations in the
      number of cases were summarized for weekdays, weekends, and different periods of
      a day in each season. We compared the differences in gender, age, body mass
      index, Marfan syndrome, hypertension, and the type of aortic dissection during
      different time periods and different seasons. In the study, 774 patients (69.1%)
      with type A aortic dissection and 347 patients (30.9%) with type B aortic
      dissection were included. The average age of 1121 patients was 51.4 +/- 12.0
      years. Overall, the peak period for the onset of aortic dissection in a day was
      between 13:00 and 18:00. There was no statistically significant difference in the
      number of cases between weekdays and weekend (P = 0.94). Most cases occurred in
      winter (30.9%); the rate of onset was the lowest in summer (16.6%). No
      statistically significant difference was observed between male and female
      patients in terms of variations during different periods of a day (P = 0.45) and
      seasons (P = 0.12). In conclusion, aortic dissection displayed circadian and
      seasonal patterns in northern China. Onset of the disease peaked between 13:00
      and 18:00 in a day. Winter was the peak season for the onset of acute aortic
      dissection, regardless of sex, type of dissection and age.

PMID- 30296182
TI  - Semaglutide once-weekly: improved efficacy with a new safety warning.
AB  - INTRODUCTION: Semaglutide once-weekly glucagon-like peptide-1 receptor agonist
      (GLP-1 RA) injection has been approved as an adjunct to diet and exercise to
      improve glycemic control in type 2 diabetes mellitus (T2DM). Areas Covered: The
      safety and efficacy of the semaglutide once-weekly injection are reviewed using
      results from preliminary pharmacology studies and later-phase randomized control
      trials (RCTs) and meta-analyses. Semaglutide once-weekly is compared to placebo
      and active comparators for T2DM in the SUSTAIN clinical trial series, with
      outcomes of: glycemic control, weight loss, major adverse cardiovascular events,
      and adverse effects. Risk for diabetic retinopathy complications (DRCs) is
      reviewed in detail, due to significantly higher risk for DRCs seen in SUSTAIN 6.
      SUSTAIN 6 is the first instance of a GLP-1 RA demonstrating significantly
      increased risk for DRCs. Semaglutide's current regulatory approvals, practice
      considerations, and cost-effectiveness compared to similar therapies are also
      considered. Expert Commentary: Semaglutide demonstrates high glycemic efficacy
      and favorable safety profile, and reduces the risk for cardiovascular events.
      Mild to moderate gastrointestinal events and retinopathy complications were more
      common with semaglutide compared to placebo, though serious adverse events were
      similar to controls and infrequent. Improved clinical efficacy should be
      carefully weighed against the risk for GI and retinopathy complications.

PMID- 30296183
TI  - Monogenic forms of lipodystrophic syndromes: diagnosis, detection, and practical
      management considerations from clinical cases.
AB  - BACKGROUND: Lipodystrophic syndromes are rare diseases of genetic or acquired
      origin characterized by partial or generalized lack of body fat. Early detection
      and diagnosis are crucial to prevent and manage associated metabolic
      dysfunctions, i.e. insulin resistance, dyslipidemia, fatty liver, and diabetes,
      and to provide appropriate genetic counseling. By means of several representative
      case studies, this article illustrates the diagnostic and management challenges
      of lipodystrophic syndromes. REVIEW: Berardinelli-Seip congenital lipodystrophy
      (BSCL) is typically diagnosed at birth, or soon thereafter, with generalized
      lipoatrophy and hepatomegaly secondary to hepatic steatosis. Physicians must also
      consider this diagnosis in adults with atypical non-autoimmune diabetes,
      hypertriglyceridemia, and a lean and muscular phenotype. The BSCL1 subtype due to
      mutations in the AGPAT2 gene can have an unusual presentation, especially in
      neonates and infants. Particular attention should be paid to infants presenting
      failure to thrive who also have hepatomegaly and metabolic derangements. The
      BSCL2 sub-type due to mutations in the BSCL gene tends to be more severe than
      BSCL1, and is characterized by greater fat loss, mild intellectual disability,
      earlier onset of diabetes, and higher incidence of premature death. Effective
      management from an earlier age may moderate the natural disease course. Partial
      lipodystrophies may easily be confused with common central obesity and/or
      metabolic syndrome. In patients with unexplained pancreatitis and
      hypertriglyceridemia, lipodystrophies such as familial partial lipodystrophy type
      2 (FPLD2; Dunnigan type, due to LMNA mutations) should be considered. Oral
      combined contraceptives, which can reveal the disease by inducing severe
      hypertriglyceridemia, are contraindicated. Endogenous estrogens may also lead to
      "unmasking" of the FPLD2 phenotype, which often appears at puberty, and is more
      severe in females than males. CONCLUSIONS: Diet and exercise, adapted to age and
      potential comorbidities, are essential prerequisites for therapeutic management
      of lipodystrophic syndromes. Metreleptin therapy can be useful to manage
      lipodystrophy-related metabolic complications.

PMID- 30296184
TI  - More than hours of work: fatigue management during high-intensity maritime
      operations.
AB  - OBJECTIVES: This study examines the impacts of peak summer demand on operator
      workload and fatigue in a maritime environment. METHODS: Participants (n = 12)
      were senior shipboard personnel who were working during the summer "double
      sailing" period for a roll-on roll-off ferry service. Wrist actigraphy was used
      to determine sleep opportunity and sleep duration, as well as prior sleep, total
      wake time, performance and alertness at the beginning and end of work periods.
      RESULTS: Contrary to expectations, sleep was significantly greater, and both
      subjective estimates of fatigue and objective neurobehavioral performance were
      not impacted negatively by periods of increased work intensity. CONCLUSIONS: This
      study highlights a number of features of a fatigue-risk management system that
      appear to have been instrumental in ensuring adequate sleep and performance was
      maintained throughout periods of increased operational intensity. As a simple
      colloquial description of the fatigue-risk management system at play in this
      operation, it was fine to "work hard" if you were able to "sleep hard" as well.

PMID- 30296185
TI  - Real-world anaplastic lymphoma kinase (ALK) rearrangement testing patterns,
      treatment sequences, and survival of ALK inhibitor-treated patients.
AB  - BACKGROUND: The anaplastic lymphoma kinase (ALK) treatment landscape is crowded
      following recent ALK inhibitor approvals, and updated information on real-world
      treatment patterns in advanced non-small-cell lung cancer (aNSCLC) with ALK
      rearrangement (ALK+) is needed. METHODS: This retrospective US cohort study used
      Flatiron Health's longitudinal electronic health record (EHR)-derived database.
      Patients (>= 18 years old) diagnosed with stage IIIB/IV aNSCLC, with documented
      ALK rearrangement and >=2 visits after January 1, 2011 were followed until
      February 28, 2016. Patients enrolled on a clinical trial or exposed to ALK
      inhibitors other than crizotinib or ceritinib were excluded. Treatment patterns,
      time and type of biomarker testing, and overall survival (OS) were analyzed.
      RESULTS: Median age (n = 300) was 62.5 years; 55% female; 48% non-smokers; 8.7%
      central nervous system (CNS) metastases at diagnosis. Overall, 73% and 86%
      received their first ALK biomarker test before/at diagnosis, or before/during
      first-line treatment, respectively. In total, 90.0%, 78.1%, and 74.7% received
      first-, second-, and third-line therapy, respectively. Most patients received ALK
      targeted treatment; 62% received crizotinib, of which 21% reported a dose
      reduction. Progression was the most common reason for crizotinib (78%) and
      ceritinib (41%) discontinuation. Median OS was 29.4 months (95% CI =24.7-39.6)
      overall; 27.1 months (95% CI =22.0-35.0) in patients with CNS metastases, and
      36.9 months (95% CI =25.1-not reached) without. CONCLUSIONS: Despite widespread
      crizotinib use in patients with ALK+ aNSCLC, a high proportion of patients
      progressed. Ongoing analyses of EHR-derived cohorts are valuable in assessing
      real-world testing rates and therapeutic use of ALK inhibitors.

PMID- 30296186
TI  - Thyroid disease in the perimenopause and postmenopause period.
AB  - The interpretation of thyroid function tests should be cautiously made during the
      perimenopause and postmenopause period bearing in mind that physiologic changes
      do exist in this group of women in terms of secretion and metabolism of
      thyrotropin and thyroid hormones. Moreover the incidence of thyroid disorders
      increases in postmenopausal and elderly women. There is no consensus for
      screening postmenopausal women even though there is well-known evidence about the
      effect of thyroid status on cognitive function, cardiovascular risk, bone
      turnover, and longevity. The diagnosis of any thyroid disorder is challenging in
      these patients because the symptoms are more subtle and attributed to menopausal
      symptoms. Management requires more attention in this population than that of
      younger groups, because high doses of L-thyroxine can lead to cardiac
      complications and increased bone turnover. Furthermore radio-iodine is preferred
      in treatment of hyperthyroidism in older patients. The risk of nodular thyroid
      disease and thyroid cancers increases in this group. Although the diagnostic
      approach is the same as for young patients, the risk of surgery is high and
      disease prognosis is worse. Women with any form of thyroid disease should be
      treated according to the current guidelines. Decision for menopausal hormonal
      therapy should be individualized regardless of the concomitant presence of
      thyroid disorders.

PMID- 30296187
TI  - Targeting central nervous system pathologies with nanomedicines.
AB  - One of the major challenges in drug development is the delivery of therapeutics
      to the central nervous system (CNS). The blood-brain barrier (BBB), which
      modulates the passage of molecules from the CNS, presents a formidable obstacle
      that limits brain uptake of therapeutics and, therefore, impedes the treatment of
      multiple neurological pathologies. Targeted nanocarriers present an excellent
      opportunity for drug delivery into the brain leveraging on endogenous receptors
      to transport therapeutics across the BBB endothelium. Receptor-mediated transport
      endows multiple benefits over other conventional delivery methods such as the
      transient permeabilization of the BBB or the direct depositioning of intracranial
      depots. Herein, different strategies for nanocarrier targeting to the CNS are
      discussed, highlighting the challenges and recent developments.

PMID- 30296188
TI  - Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia.
AB  - INTRODUCTION: Cellular immunotherapy with autologous or allogeneic T cells,
      genetically engineered to express chimeric antigen receptors (CARs) or T-cell
      receptors, in order to redirect their cytotoxic specificity toward malignant
      cells, is emerging as a promising new treatment modality. The most advanced
      approach in clinical development is the use of anti-CD19 CAR T-cells for the
      treatment of CD19+ B-cell malignancies, including acute lymphocytic leukemia
      (ALL). Areas covered: Recently, the Food and Drug Administration (FDA) approved
      the first anti-CD19 CAR T-cell product, tisagenlecleucel, for the treatment of
      pediatric and young adult patients with relapsed/refractory ALL. In this
      overview, we described the advances in the field, including a summary of clinical
      trials with tisagenlecleucel in ALL published to date. Expert opinion: CAR T-cell
      therapy has been developed in the context of small clinical studies and very few
      centers have had to deal with the challenges of managing CAR T-cells
      administration. However, this approach is likely to become a standard option for
      patients with relapsed/refractory B-cell lineage ALL.

PMID- 30296190
TI  - Clostridium difficile infection in oncology patients: epidemiology,
      pathophysiology, risk factors, diagnosis, and treatment.
AB  - Clostridium difficile infection (CDI) is one of the most common healthcare
      associated infections in the United States. Its incidence has been increasing in
      the recent years despite preventative measures. CDI increases annual expenses by
      1.5 billion dollars. Cancer patients are at higher risk to acquire CDI, as
      explained by their frequent exposure to risk factors. CDI in cancer patients is
      associated with higher mortality rates and prolonged hospitalization.
      Furthermore, CDI affects the course of the disease by delaying treatments such as
      chemotherapy. Chemotherapeutics drugs are considered independent risk factors for
      CDI. This review discusses Clostridium difficile infection in cancer patients,
      including those who are receiving chemotherapy. Herein, we summarize recent data
      regarding the epidemiology, risk factors, including chemotherapy regimens,
      pathogenesis, diagnostic techniques and treatment options, including newer
      agents. Method: A literature search was performed using the PubMed and Google
      Scholar databases. The MeSH terms utilized in different combinations were
      'clostridium difficile', 'neoplasia/cancer/oncology', 'chemotherapy',
      'diagnosis', and 'treatment', in addition to looking up each treatment option
      individually to generate a comprehensive search. The articles were initially
      screened by title alone, followed by screening through abstracts. Full texts of
      pertinent articles (including letters to editors, case reports, case series,
      cohort studies, and clinical trials) were included in this review.

PMID- 30296189
TI  - Parental stress and paediatric acquired brain injury.
AB  - OBJECTIVE: Studies on parental stress following childhood acquired brain injury
      (ABI-including brain tumours (BT) and other brain injuries) are scarce. The aim
      of this study was to assess maternal stress in a sample of children and
      adolescents diagnosed with severe paediatric ABI. METHODS: Seventy-eight French
      speaking mothers of 37 with BT and 41 with other ABIs completed the Paediatric
      Inventory for Parents (PIP), the State-Trait Anxiety Inventory (STAI) and the
      Family Assessment Device (FAD) at a mean time since diagnosis of 1.5 years.
      RESULTS: The PIP correlated significantly with the STAI and the FAD. Socio
      demographic factors, such as the age of mother and child, and the mother's
      educational level, were correlated with both maternal stress and anxiety.
      Maternal stress scores were comparable between groups. Emotional functioning was
      the most markedly affected domain, followed by parental role. CONCLUSIONS:
      Emotional stress as assessed by the PIP in mothers of children with ABI is
      significant and should motivate specific psychosocial interventions.

PMID- 30296191
TI  - The protective role of endogenous n-3 polyunsaturated fatty acids in Tau
      Alzheimer's disease mouse model.
AB  - OBJECTIVES: The role of n-3 polyunsaturated fatty acid (PUFA) as the main
      docosahexaenoic acid (DHA) in Alzheimer's disease (AD) remains controversial. Our
      study aimed to provide detailed information about the role of endogenous n-3
      PUFAs in AD. METHODS: Here, we generated a fat-1/tau transgenic mouse AD model by
      crossing female tau mice with male fat-1 mice to exclude confounding variables
      associated with the benefit of a DHA diet in these AD mice models. PUFAs
      presented in these AD models were detected by gas chromatography, and the role of
      endogenous n-3 PUFAs was assessed by lifespan survival assay, behavioral,
      pathologic, and molecular biology testing as well as imaging of cerebral
      vasculature. RESULTS: Endogenous n-3 PUFAs were shown to improve the memory and
      learning ability of AD mice. One possible reason for this improvement is the
      reduced formation of neurotrophic factors (NFTs) and Abeta amyloid plaques which
      usually damage hippocampal neurons. Additionally, endogenous n-3 PUFAs were
      demonstrated to protect cerebral vascular of AD mice, thereby increasing brain
      metabolism. Besides, endogenous n-3 PUFAs were observed to extend of the overall
      survival of tau mouse models. CONCLUSION: Endogenous n-3 PUFAs delayed the onset
      of Alzheimer's disease caused by tau protein dysfunction, alleviating related
      symptoms and significantly prolonging survival in vivo.

PMID- 30296192
TI  - Postoperative Management of Resected Brain Metastases: When Can Radiotherapy Be
      Deferred?
AB  - The Oncology Grand Rounds series is designed to place original reports published
      in the Journal into clinical context. A case presentation is followed by a
      description of diagnostic and management challenges, a review of the relevant
      literature, and a summary of the authors' suggested management approaches. The
      goal of this series is to help readers better understand how to apply the results
      of key studies, including those published in Journal of Clinical Oncology, to
      patients seen in their own clinical practice. A 67-year-old woman was diagnosed
      17 months ago with stage IIIB non-small-cell lung cancer (NSCLC; adenocarcinoma),
      without a targetable mutation, for which she received chemotherapy and thoracic
      radiotherapy. She developed new-onset gait ataxia, nausea, morning emesis, and
      headaches. A brain magnetic resonance imaging (MRI) scan demonstrated a 3.2-cm
      left cerebellar enhancing metastatic lesion, with surrounding vasogenic edema and
      mass effect, and three additional enhancing cortical, parenchymal lesions, each <
      1.2 cm in maximum diameter, and none with significant mass effect ( Fig 1A ). A
      restaging positron emission tomography scan revealed no new sites of metastatic
      disease and no obvious intrathoracic progression. She underwent craniotomy, with
      piecemeal resection of the cerebellar metastatic lesion that proved to be
      recurrent lung cancer ( Fig 1B ). Her medical history was significant for mild
      hypertension and diet-controlled type II diabetes. She had smoked one pack a day
      for 32 years and had quit 3 years earlier. Postoperatively, her neurologic
      symptoms resolved, and physical and neurologic examinations were unrevealing; she
      had an Eastern Cooperative Oncology Group performance status (PS) of 0 and a Mini
      Mental State Examination (MMSE) score of 29 of 30. A 3-week postoperative MRI
      scan confirmed the presence of 1-cm right frontal, 1.2-cm right parietal, and 1.2
      cm left temporal enhancing lesions with minimal enhancement and no evidence of
      mass effect or edema. In addition, there was an ill-defined residual tumor bed,
      estimated to be approximately 3.7 cm in maximum diameter ( Fig 1C ). The patient
      was no longer receiving any steroids and was not receiving any anticonvulsants.
      Because of the residual three brain metastatic lesions, as well as the
      consideration of a high risk of surgical failure, she was referred for
      radiotherapy.

PMID- 30296194
TI  - Introduction of universal infant hepatitis B immunisation in the UK- paving the
      way to elimination.
AB  - In May 2016, the World Health Assembly ratified the first ever Global Health
      Sector Strategy (GHSS) on Viral Hepatitis to eliminate viral hepatitis as a
      public health threat by 2030. In pursuit of this elimination goal and recognising
      that hepatitis control through immunisation is an essential foundation of a
      hepatitis B prevention programme, the World Health Organization set out vaccine
      coverage targets for both universal and selective childhood immunisation
      programmes, focusing on preventing mother to child transmission. In August 2017
      the UK introduced a hexavalent (DTaP/IPV/Hib/HepB) combination vaccine into the
      routine childhood immunisation programme, replacing the pentavalent vaccine given
      to all infants at 8, 12 and 16 weeks. With the addition of the 6th component to
      protect against hepatitis B the UK finally introduced universal hepatitis B
      immunisation. Prior to that, the UK had a selective immunisation policy targeting
      high risk groups for hepatitis B - including infants born to hepatitis B infected
      mothers. We tell the story of hepatitis B vaccination in the UK, and how we have
      evolved from selective to a universal infant immunisation programme, the factors
      considered in hepatitis B vaccine policy decision-making, and the progress
      towards elimination of viral hepatitis as a public health threat.

PMID- 30296193
TI  - Multirefractory primary immune thrombocytopenia; targeting the decreased sialic
      acid content.
AB  - Patients with multirefractory immune thrombocytopenia (ITP) have limited
      treatment options. Recent data suggest that specific anti-platelet antibodies may
      cause destruction of platelets by favoring platelet loss of sialic acid. In this
      multicenter study 35 patients with ITP, including 16 with multirefractory
      disease, were analyzed for antiplatelet-antibodies, thrombopoietin (TPO) levels,
      and platelet desialylation. In selected cases, responses to a novel treatment
      strategy using oseltamivir were tested. We found that antibodies against
      GPIbalpha were overrepresented in multirefractory patients compared to responders
      (n = 19). In contrast to conventional ITP patients, multirefractory patients
      exhibited a significant increased platelet activation state (granule secretion)
      and desialylation (RCA-1 binding) (p < 0.05), and a trend toward higher plasma
      TPO concentrations. The decreased sialic acid content seemed to be restricted to
      platelet glycoproteins, since other plasma proteins were not hypoglycosylated. A
      total of 10 patients with multirefractory ITP having remarkable loss of platelet
      terminal sialic acids were given oseltamivir phosphate. When the antiviral drug
      was combined with TPO receptor agonists (TPO-RAs) or with immunosuppressant
      drugs, platelet responses were observed in 66.7% of patients. All responding
      patients presented with antibodies reactive only against GPIbalpha. These
      findings suggest that desialylation may play a key pathogenic role in some
      multirefractory ITP patients, and provide diagnostic tools for the identification
      of such patients. Furthermore, we show that sialidase inhibitor treatment in
      combination with therapies that help to increase platelet production can induce
      sustained platelet responses in some patients with anti-GPIbalpha -mediated
      thrombocytopenia that have failed previous therapies.

PMID- 30296195
TI  - Isolated central nervous system Rosai-Dorfman disease and breast cancer: an
      unusual presentation.
AB  - The association between Rosai-Dorfman Disease (RDD) and cancer was reported for
      the first time in 1984. However, there are still a small number of reports of
      this association. We describe a 60-year-old woman who presented with a focal
      onset motor seizure followed by tonic-clonic generalization and persistent
      headache. Magnetic Resonance Imaging disclosed an irregular hyperintense lesion
      in T2 and vasogenic edema in the left parietal region. Immunohistochemical
      analysis of a biopsy fragment was positive for protein S-100 and CD68 and
      negative for CD1a, compatible with the diagnosis of RDD. She previously had
      breast cancer six years earlier and had used tamoxifen for two years and
      anostrozol for three years after diagnosis of cancer. RDD has been already
      associated with different cancers, such as Hodgkin's lymphoma, non-Hodgkin's
      lymphoma, follicular lymphoma, melanoma, adenocarcinoma and small cell lung
      cancer. As far as we know, this is the first report of an association between
      breast cancer and RDD.

PMID- 30296196
TI  - Iodine-125 seed implantation combined with arterial chemoembolization therapy for
      pain palliation in metastatic bone cancer: a retrospective study.
AB  - Bone metastases are the most common sites for malignant tumors. Patients who
      failed to respond to initial first-line treatment with bisphosphonates usually
      suffer from extreme pain. The aim of this study was to observe the efficacy of
      arterial chemoembolization combined with Iodine-125 seed implantation in the
      treatment of bone metastatic cancer pain. All 14 patients with metastatic bone
      tumor wo failed first-line treatment underwent arterial chemoembolization the day
      before the implantation of the particles. A computer stereoscopic TPS was used to
      design the treatment plans, the number and dose of particles required for
      implantation. Pain relief was evaluated using several parameters such as Visual
      Analog Scale (VAS) and Verbal Rating Scales (VRS). Pain intensity was measured
      pre-operation and 1-week, 1-month, 3-month after the treatment. Meanwhile, we
      also assessed tumor size using computer tomography (CT). Pain palliation was
      observed in 35.7% (5/14), 57.1% (8/14), and 78.6% (11/14) of all patients at 1
      week, 1-month and 3-month post treatment. Likewise, our analysis showed that the
      combination therapy resulted in a significant decrease of VAS score (6.71 +/-
      0.49 before treatment vs 3.36 +/- 0.40 at 3 month post treatment) and overall
      responding rate of 92.0% using VRS pain assessment. Consistently, tumor size was
      reduced from 42.16 +/- 10.32 before treatment to 29.11 +/- 8.73 at 3 months post
      treatment. No serious complications were detected. Our study demonstrate that the
      combination of arterial chemoembolization and 125I particles resulted in evident
      pain relief and reduction of tumor burden, suggesting that the combination
      treatment could be a feasible and promising therapy for bone tumor management.

PMID- 30296197
TI  - Recent changes in the epidemiology of Neisseria meningitidis serogroup W across
      the world, current vaccination policy choices and possible future strategies.
AB  - Invasive meningococcal disease (IMD) is a serious disease that is fatal in 5-15%
      and disabling in 12-20% of cases. The dynamic and unpredictable epidemiology is a
      particular challenge of IMD prevention. Although vaccination against
      meningococcal serogroups A (MenA), MenC and, more recently, MenB, are proving
      successful, other serogroups are emerging as major IMD causes. Recently, surges
      in MenW incidence occurred in South America, Europe, Australia and parts of sub
      Saharan Africa, with hypervirulent strains being associated with severe IMD and
      higher fatality rates. This review describes global trends in MenW-IMD
      epidemiology over the last 5-10 years, with emphasis on the response of
      national/regional health authorities to increased MenW prevalence in impacted
      areas. Several countries (Argentina, Australia, Chile, the Netherlands and UK)
      have implemented reactive vaccination campaigns to reduce MenW-IMD, using MenACWY
      conjugate vaccines. Future vaccination programs should consider the evolving
      epidemiology of MenW-IMD and the most impacted age groups.

PMID- 30296198
TI  - Evaluation of similar quality attribute characteristics in SB5 and reference
      product of adalimumab.
AB  - Biosimilars are biologic products that are highly similar to a licensed reference
      product in terms of quality, safety, and efficacy. SB5 is a biosimilar of
      Humira(r) (adalimumab) developed by Samsung Bioepis. To demonstrate its
      biosimilarity in quality to Humira(r), we performed a comprehensive
      characterization in terms of structure, physicochemical properties, and
      biological properties following the International Conference on Harmonization, US
      Food and Drug Administration, and European Medicines Agency guidelines. We
      analyzed all available batches of SB5 and more than 100 EU- and US-sourced lots
      of Humira(r) using state-of-the-art methods whenever possible, and compared the
      two sets of data. The structural properties comprised primary and higher-order
      structures and N-glycosylation. The physicochemical characteristics were
      categorized into liquid chromatographic patterns and electrophoretic pattern
      concerning size and charge heterogeneity. The biological properties were examined
      by in vitro functional assays. Overall, SB5 and Humira(r) were shown to be
      similar to each other in terms of quality attributes. For some of the quality
      attributes, minor differences were observed. However, the observed differences
      have been adequately addressed and demonstrated these do not translate into
      clinically meaningful differences in terms of safety, purity, and potency.

PMID- 30296199
TI  - Lp-PLA2 as a risk factor of early neurological deterioration in acute ischemic
      stroke with TOAST type of large arterial atherosclerosis.
AB  - INTRODUCTION: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a well-known
      risk factor of atherosclerotic vascular diseases. Nevertheless, its role in the
      acute phase of ischemic stroke is still unclear. The aim of this study is to
      identify the relationship between Lp-PLA2 levels and early neurological
      deterioration (END) in acute ischemic stroke patients with Trial of Org 10 172 in
      Acute Stroke Treatment (TOAST) subtype of large arterial atherosclerosis (LAA).
      METHODS: We enrolled Chinese patients with first ever acute ischemic stroke
      admitted to Neurology Department of Shenzhen Second People's Hospital within 48 h
      from onset of symptoms during January - November 2015. Demographic and laboratory
      information were collected while END was defined as an increase in the National
      Institute of Health Stroke Scale score by >= 1 point in motor power, or >= 2
      points in the total score within 10 days after admission. RESULTS: Overall 181
      patients were involved; END was diagnosed in 30 patients within 10 days after
      admission. The odds ratio for END increased with increasing levels of Lp-PLA2
      (intermediate level, OR = 1.96, 95%CI 1.02-4.27, p = 0.041; high level, OR =
      2.99, 95%CI 1.26-5.73, p = 0.023). Conclution: Intermediate and high level of Lp
      PLA2 was identified as independent predictor of END in multivariate analysis. Lp
      PLA2 could be valued as a risk factor of END in patients with acute ischemic
      stroke with TOAST subtype of LAA.

PMID- 30296200
TI  - Expression, purification, and characterization of N-terminal His-tagged proteins
      with mutations in zinc finger 3 of zinc finger protein ZNF191(243-368).
AB  - Zinc finger protein ZNF191(243-368), the zinc finger region of ZNF191, is
      potentially associated with cell proliferation in hepatocellular carninoma. A His
      tag expression system was used to express and purify proteins with mutations in
      the zinc finger 3 of ZNF191(243-368) for analysis of protein properties,
      structure, and functions. The purification of the His-tag fusion proteins was
      simpler and faster than that of the ZNF191(243-368) inclusion bodies. The
      properties and structures of the His-tag fusion mutant proteins were investigated
      using spectrographic techniques and DNA hydrolysis experiment. The His6-tag
      system could be used to express ZNF191(243-368). The presence of the His6-tag at
      the N-terminus of ZNF191(243-368) did not evidently affect its properties and
      structure. However, the site-directed mutations in zinc finger 3 affected the
      structure of the protein. The DNA hydrolase activity of His6-ZF-F3/H4 suggested
      that four histidines in zinc finger 3 might form a structure similar to that of
      the active center in a hydrolase. This work reports that continuous histidines
      need to form a certain structure for specific functions, and provides new
      insights into the design of an artificial nuclease.

PMID- 30296202
TI  - Participants' perceptions of an aphasia-friendly occupational therapy home
      program.
AB  - BACKGROUND: Upper extremity impairments post-stroke impact participation in
      valued occupations. Home programs are used to extend the frequency and amount of
      upper extremity practice for people post-stroke, but novel ways of increasing
      adherence to these programs is needed to ensure intense repetitive practice.
      OBJECTIVES: The purpose of this process evaluation, was to examine the
      perceptions of people with aphasia as it relates to modifications to home
      programs that could influence participation, specifically listening to music and
      aphasia-friendly adaptations of written materials. METHODS: Seven people with
      chronic aphasia completed an upper extremity home program that included the use
      of music and aphasia-friendly modified materials (ClinicalTrials.gov
      ID:2016/06/18). After the home program, participants completed semi-structured
      interviews to understand their perceptions of the program and the modifications.
      RESULTS: Five themes were identified including (1) music, (2) activities, (3)
      instructions, (4) logistics, and (5) progress. Most participants perceived music
      as helpful, but a few reported it being distracting. Participants found the
      variety of activities helpful as well as specific characteristics of the
      instructions such as photographs and images. Some participants expressed elements
      of the home program to be barriers to practice such as using the activity
      monitors and logbook, which required assistance at times. Finally, participants
      noted their own progress resulting from the program and liked that they could
      adjust the intensity of the program as they progressed. CONCLUSIONS: Overall
      participants in this study with aphasia perceived the modifications to home
      programs including aphasia friendly written instructions and music to facilitate
      successful home practice.

PMID- 30296201
TI  - PHYTOCHROME INTERACTING FACTOR1 interactions leading to the completion or
      prolongation of seed germination.
AB  - In Arabidopsis thaliana, the basic Helix Loop Helix transcription factor,
      PHYTOCHROME INTERACTING FACTOR1 (PIF1) is known to orchestrate the seed
      transcriptome such that, ultimately, proteins repressing the completion of
      germination are produced in darkness. While PIF1-mediated control of abscisic
      acid (ABA) and gibberellic acid (GA) anabolism/catabolism is indirect, PIF1
      action favors ABA while discriminating against GA, firmly establishing ABA's
      repressive influence on the completion of germination. The result is tissue that
      is more sensitive to and producing more ABA; and is less responsive to and
      deficient in GA. Illumination of the appropriate wavelength activates phytochrome
      which enters the nucleus, and binds to PIF1, initiating PIF1's phosphorylation by
      diverse kinases, subsequent polyubiquitination, and hydrolysis. One mechanism by
      which phosphorylated PIF1 is eliminated from the cells of the seed upon
      illumination involves an F-BOX protein, COLD TEMPERATURE GERMINATING10 (CTG10).
      Discovered in an unbiased screen of activation tagged lines hastening the
      completion of seed germination at 10 degrees C, one indirect consequence of CTG10
      action in reducing PIF1 titer, should be to enhance the transcription of genes
      whose products work to increase bioactive GA titer, shifting the intracellular
      milieu from one that is repressive to, toward one conducive to, the completion of
      seed germination. We have tested this hypothesis using a variety of Arabidopsis
      lines altered in CTG10 amounts. Here we demonstrate using bimolecular
      fluorescence complementation that PIF1 interacts with CTG10 and show that, in
      light exposed seeds, PIF1 is more persistent in ctg10 relative to WT seeds while
      it is less stable in seeds over-expressing CTG10. These results are congruent
      with the relative transcript abundance from three genes whose products are
      involved in bioactive GA accumulation. We put forth a model of how PIF1
      interactions in imbibed seeds change during germination and how a permissive
      light signal influences these changes, leading to the completion of germination
      of these positively photoblastic propagules.

PMID- 30296203
TI  - The role of cellular contact and TGF-beta signaling in the activation of the
      epithelial mesenchymal transition (EMT).
AB  - The epithelial mesenchymal transition (EMT) is one step in the process through
      which carcinoma cells metastasize by gaining the cellular mobility associated
      with mesenchymal cells. This work examines the dual influence of the TGF-beta
      pathway and intercellular contact on the activation of EMT in colon (SW480) and
      breast (MCF7) carcinoma cells. While the SW480 population revealed an
      intermediate state between the epithelial and mesenchymal states, the MC7 cells
      exhibited highly adhesive behavior. However, for both cell lines, an exogenous
      TGF-beta signal and a reduction in cellular confluence can push a subgroup of the
      population towards the mesenchymal phenotype. Together, these results highlight
      that, while EMT is induced by the synergy of multiple signals, this activation
      varies across cell types.

PMID- 30296204
TI  - Comprehensive characterisation of the heterogeneity of adalimumab via charge
      variant analysis hyphenated on-line to native high resolution Orbitrap mass
      spectrometry.
AB  - Charge variant analysis is a widely used tool to monitor changes in product
      quality during the manufacturing process of monoclonal antibodies (mAbs).
      Although it is a powerful technique for revealing mAb heterogeneity, an
      unexpected outcome, for example the appearance of previously undetected isoforms,
      requires further, time-consuming analysis. The process of identifying these
      unknowns can also result in unwanted changes to the molecule that are not
      attributable to the manufacturing process. To overcome this, we recently reported
      a method combining highly selective cation exchange chromatography-based charge
      variant analysis with on-line mass spectrometric (MS) detection. We further
      explored and adapted the chromatographic buffer system to expand the application
      range. Moreover, we observed no salt adducts on the native protein, also
      supported by the optimal choice of MS parameters, resulting in increased data
      quality and mass accuracy. Here, we demonstrate the utility of this improved
      method by performing an in-depth analysis of adalimumab before and after forced
      degradation. By combining molecular mass and retention time information, we were
      able to identify multiple modifications on adalimumab, including lysine
      truncation, glycation, deamidation, succinimide formation, isomerisation, N
      terminal aspartic acid loss or C-terminal proline amidation and fragmentation
      along with the N-glycan distribution of each of these identified proteoforms.
      Host cell protein (HCP) analysis was performed using liquid chromatography-mass
      spectrometry that verified the presence of the protease Cathepsin L. Based on the
      presence of trace HCPs with catalytic activity, it can be questioned if
      fragmentation is solely driven by spontaneous hydrolysis or possibly also by
      enzymatic degradation.

PMID- 30296205
TI  - HIV and tuberculosis co-infection in a highly HIV-infected population of rivers
      state, Nigeria.
AB  - Human Immunodeficiency Virus (HIV) and tuberculosis (TB) are considered as key
      players in the global health scene. This study sought to determine the prevalence
      of TB among HIV-positive attendees of the Directly Observed Treatment of Short
      Course (DOTS) program at the military hospital in Port Harcourt. The association
      of HIV prevalence with gender and age as risk factors was also determined. A
      total of 200 patients aged 15-65 years were screened. Re-screening for HIV was
      done for confirmation. The overall prevalence for anti-TB antibodies amongst HIV
      positive individuals was 14.0% (7.5% in males and 6.5% in females) while HIV
      prevalence following re-screening was 92%. It was observed that based on
      employment status and level of education, the highest HIV prevalence was seen in
      unemployed individuals and individuals with no formal education. The result
      showed that 29.9% of the HIV seropositives were males while 70.1% were females.
      Sex-related prevalence of HIV-TB coinfection within groups indicated
      significantly higher co-infection rates (P < 0.05) among males (23.1%) than
      females (9.6%). Age-related prevalence of HIV-TB coinfection within groups showed
      that co-infection was significantly greater (P < 0.05) in ages below 30 years
      (21.2%) than in their counterparts 30 years and above (9.6%). This study
      confirmed the presence of TB co-infections among HIV-positive individuals in Port
      Harcourt, Nigeria. Considering the role of TB in driving the HIV pandemic, it is
      imperative that HIV-positive patients are screened for TB infection regularly to
      reduce the scale of active HIV-TB co-infection.

PMID- 30296206
TI  - Zn-fortified cereal grains in field-grown barley by enhanced root cytokinin
      breakdown.
AB  - Zinc (Zn) is an essential element in human nutrition. The concentration of Zn in
      cereals, which is a staple food in developing countries, is often too low thus
      contributing to Zn malnutrition in nearly two billion people worldwide. We have
      reported recently that transgenic barley plants expressing a cytokinin-degrading
      CYTOKININ OXIDASE/DEHYDROGENASE (CKX) gene in their roots form a larger root
      system and accumulate a higher concentration of Zn in their grains when grown
      under greenhouse conditions. Here, we have tested this trait under field
      conditions. Four independent pEPP:CKX lines accumulated an up to 30% higher Zn
      concentration in their grains as compared to the untransformed control suggesting
      that this is a stable trait. The increased Zn concentration exceeded the limit
      set by the HarvestPlus program for wheat. We, therefore, propose that root
      enhancement achieved by increased degradation of cytokinin in roots can be a
      sustainable strategy to combat malnutrition caused by Zn deficiency.

PMID- 30296207
TI  - Biological Event Trigger Identification with Noise Contrastive Estimation.
AB  - Biological Event Extraction is an important task towards the goal of extracting
      biomedical knowledge from the scientific publications by capturing biomedical
      entities and their complex relations from the texts. As a crucial step in event
      extraction, event trigger identification, assigning words with suitable trigger
      category, has recently attracted substantial attention. As triggers are scattered
      in large corpus, traditional linguistic parsers are hard to generate syntactic
      features from them. Thereby, trigger sparsity problem restricts the model's
      learning process and becomes one of the main hinder in trigger identification. In
      this paper, we employ Noise Contrastive Estimation with Multi-Layer Perceptron
      model for solving triggers' sparsity problem. Meanwhile, in the light of recent
      advance in word distributed representation, word-embedding feature generated by
      language model is utilized for semantic and syntactic information extraction.
      Finally, experimental study on commonly used MLEE dataset against baseline
      methods has demonstrated its promising result.

PMID- 30296208
TI  - 3D Measurements of Acceleration-Induced Brain Deformation via Harmonic Phase
      Analysis and Finite-Element Models.
AB  - OBJECTIVE: To obtain dense spatiotemporal measurements of brain deformation from
      two distinct but complementary head motion experiments: linear and rotational
      accelerations. METHODS: This study introduces a strategy for integrating harmonic
      phase analysis of tagged magnetic resonance imaging (MRI) and finite element
      models to extract mechanically representative deformation measurements. The
      method was calibrated using simulated as well as experimental data, demonstrated
      in a phantom including data with image artifacts, and used to measure brain
      deformation in human volunteers undergoing rotational and linear acceleration.
      RESULTS: Evaluation methods yielded a displacement error of 1.1 mm compared to
      human observers, and strain errors between 0.1 0.2% (mean std. dev.) for linear
      acceleration and 0.7 0.3% for rotational acceleration. In the presence of
      inconsistent or missing data, we demonstrate an approach that can provide an
      error reduction of 86%. Analysis of results shows consistency with 2D motion
      estimation, agreement with external sensors, and the expected physical behavior
      of the brain. CONCLUSION: Mechanical regularization is useful for obtaining dense
      spatiotemporal measurements of in-vivo brain deformation under different loading
      regimes. SIGNIFICANCE: The measurements suggest that the brain's 3D response to
      mild accelerations includes distinct patterns observable using practical MRI
      resolutions. This type of measurement can provide validation data for computer
      models for the study of traumatic brain injury (TBI).

PMID- 30296209
TI  - Half Thresholding Pursuit Algorithm for Fluorescence Molecular Tomography.
AB  - OBJECTIVE: Fluorescence Molecular Tomography (FMT) is a promising optical tool
      for small animal imaging. The -norm regularization has attracted attention in the
      field of FMT due to its ability in enhancing sparsity of solution and coping with
      the high ill-posedness of the inverse problem. However, efficient algorithm for
      solving the non-convex regularized model deserve to explore. METHOD: A Half
      Thresholding Pursuit Algorithm (HTPA) combined with parameter optimization is
      proposed in this paper to efficiently solve the non-convex optimization model.
      Specifically, the half thresholding iteration method is utilized to solve -norm
      model, pursuit strategy is used to accelerate the process of iteration, and the
      parameter optimization scheme is designed to obtain robust parameter. RESULTS:
      Analysis and assessment on simulated and experimental data demonstrate that the
      proposed HTPA performs better in location accuracy and reconstructed fluorescent
      yield in less time cost, compared with the state-of-the-art reconstruction
      algorithms. CONCLUSION: The proposed HTPA combined with the parameter
      optimization scheme is an efficient and robust reconstruction approach to FMT.

PMID- 30296210
TI  - Estimating Missing Data in Temporal Data Streams Using Multi-directional
      Recurrent Neural Networks.
AB  - OBJECTIVE: Missing data is a ubiquitous problem. It is especially challenging in
      medical settings because many streams of measurements are collected at different 
      and often irregular - times. Accurate estimation of those missing measurements
      is critical for many reasons, including diagnosis, prognosis and treatment.
      Existing methods address this estimation problem by interpolating within data
      streams or imputing across data streams (both of which ignore important
      information) or ignoring the temporal aspect of the data and imposing strong
      assumptions about the nature of the data-generating process and/or the pattern of
      missing data (both of which are especially problematic for medical data). We
      propose a new approach, based on a novel deep learning architecture that we call
      a Multi-directional Recurrent Neural Network (M-RNN) that interpolates within
      data streams and imputes across data streams. We demonstrate the power of our
      approach by applying it to five real-world medical datasets. We show that it
      provides dramatically improved estimation of missing measurements in comparison
      to 11 state-of-the-art benchmarks (including Spline and Cubic Interpolations,
      MICE, MissForest, matrix completion and several RNN methods); typical
      improvements in Root Mean Square Error are between 35% - 50%. Additional
      experiments based on the same five datasets demonstrate that the improvements
      provided by our method are extremely robust.

PMID- 30296211
TI  - A Patient-specific Approach for Short-term Epileptic Seizures Prediction through
      the Analysis of EEG synchronization.
AB  - Epilepsy is a neurological disorder arising from anomalies of the electrical
      activity in the brain, affecting about 65 millions individuals worldwide.
      {Objective:} This work proposes a patient-specific approach for short-term
      prediction (i.e., within few minutes) of epileptic seizures. {Methods:} We use
      noninvasive EEG data, since the aim is exploring the possibility of developing a
      noninvasive monitoring/control device for the prediction of seizures. Our
      approach is based on finding synchronization patterns in the EEG that allow to
      distinguish in real time preictal from interictal states. In practice, we develop
      easily computable functions over a graph model to capture the variations in the
      synchronization, and employ a classifier for identifying the preictal state.
      {Results:} We compare two state-of-the-art classification algorithms and a simple
      and computationally inexpensive threshold-based classifier developed ad hoc.
      Results on publicly available scalp EEG database and on data of the patients of
      the Unit of Neurology and Neurophysiology at University of Siena show that this
      simple and computationally viable processing is able to highlight the changes in
      synchronization when a seizure is approaching. {Conclusion and significance:} The
      proposed approach, characterized by low computational requirements and by the use
      of noninvasive techniques, is a step toward the development of portable and
      wearable devices for real-life use.

PMID- 30296212
TI  - Learning Compact Features for Human Activity Recognition via Probabilistic First
      Take-All.
AB  - With the popularity of mobile technology, wearable devices, such as smart
      wristbands and smartphones, open a unprecedented opportunity to solve the
      challenging human activity recognition (HAR) problem by learning expressive
      representations from the multi-dimensional sensor signals that record huge
      amounts of daily activities. This inspires us to develop a new algorithm
      applicable to both camera-based and wearable sensor-based HAR systems. Although
      competitive classification accuracy has been reported, existing methods often
      face the challenge of distinguishing visually similar activities composed of
      activity patterns in different temporal orders. In this paper, we propose a novel
      probabilistic algorithm to compactly encode temporal orders of activity patterns
      for HAR. Specifically, the algorithm learns an optimal set of latent patterns
      such that their temporal structures really matter in recognizing different human
      activities. Then a novel probabilistic First-Take-All (pFTA) approach is
      introduced to generate compact features from the orders of these latent patterns
      to encode an entire sequence, and the temporal structural similarity between
      different sequences can be efficiently computed by the Hamming distance between
      compact features. Experiments on three public HAR datasets show the proposed pFTA
      approach can achieve competitive performance in terms of accuracy as well as
      efficiency.

PMID- 30296213
TI  - Shallowing Deep Networks: Layer-wise Pruning based on Feature Representations.
AB  - Recent surge of Convolutional Neural Networks (CNNs) has brought successes among
      various applications. However, these successes are accompanied by a significant
      increase in computational cost and the demand for computational resources, which
      critically hampers the utilization of complex CNNs on devices with limited
      computational power. In this work, we propose a feature representation based
      layer-wise pruning method that aims at reducing complex CNNs to more compact ones
      with equivalent performance. Different from previous parameter pruning methods
      that conduct connection-wise or filter-wise pruning based on weight information,
      our method determines redundant parameters by investigating the features learned
      in the convolutional layers and the pruning process is operated at a layer level.
      Experiments demonstrate that the proposed method is able to significantly reduce
      computational cost and the pruned models achieve equivalent or even better
      performance compared to the original models on various datasets.

PMID- 30296214
TI  - Learning compact q-space representations for multi-shell diffusion-weighted MRI.
AB  - Diffusion-weighted MRI measures the direction and scale of the local diffusion
      process in every voxel through its spectrum in q-space, typically acquired in one
      or more shells. Recent developments in microstructure imaging and multi-tissue
      decomposition have sparked renewed attention in the radial b-value dependence of
      the signal. Applications in motion correction and outlier rejection therefore
      require a compact linear signal representation that extends over the radial as
      well as angular domain. Here, we introduce SHARD, a data-driven representation of
      the q-space signal based on spherical harmonics and a radial decomposition into
      orthonormal components. This representation provides a complete, orthogonal
      signal basis, tailored to the spherical geometry of q-space and calibrated to the
      data at hand. We demonstrate that the rank-reduced decomposition outperforms
      model-based alternatives in human brain data, whilst faithfully capturing the
      micro-and meso-structural information in the signal. Furthermore, we validate the
      potential of joint radial-spherical as compared to single-shell representations.
      As such, SHARD is optimally suited for applications that require low-rank signal
      predictions, such as motion correction and outlier rejection. Finally, we
      illustrate its application for the latter using outlier robust regression.

PMID- 30296215
TI  - Three-Dimensional Quantification of Filopodia in Motile Cancer Cells.
AB  - We present a three-dimensional bioimage analysis workflow to quantitatively
      analyze single, actin-stained cells with filopodial protrusions of diverse
      structural and temporal attributes, such as number, length, thickness, level of
      branching, and lifetime, in time-lapse confocal microscopy image data. Our
      workflow makes use of convolutional neural networks trained using real as well as
      synthetic image data, to segment the cell volumes with highly heterogeneous
      fluorescence intensity levels and to detect individual filopodial protrusions,
      followed by a constrained nearest-neighbor tracking algorithm to obtain valuable
      information about the spatio-temporal evolution of individual filopodia. We
      validated the workflow using real and synthetic 3D time-lapse sequences of lung
      adenocarcinoma cells of three morphologically distinct filopodial phenotypes and
      show that it achieves reliable segmentation and tracking performance, providing a
      robust, reproducible and less time-consuming alternative to manual analysis of
      the 3D+t image data.

PMID- 30296216
TI  - Separating Touching Cells using Pixel Replicated Elliptical Shape Models.
AB  - One of the most important and error-prone tasks in biological image analysis is
      the segmentation of touching or overlapping cells. Particularly for optical
      microscopy, including transmitted light and confocal fluorescence microscopy,
      there is often no consistent discriminative information to separate cells that
      touch or overlap. It is desired to partition touching foreground pixels into
      cells using the binary threshold image information only, and optionally
      incorporating gradient information. The most common approaches for segmenting
      touching and overlapping cells in these scenarios are based on the watershed
      transform. We describe a new approach called pixel replication for the task of
      segmenting elliptical objects that touch or overlap. Pixel replication uses the
      image Euclidean distance transform in combination with Gaussian mixture models to
      better exploit practically effective optimization for delineating objects with
      elliptical decision boundaries. Pixel replication improves significantly on
      commonly used methods based on watershed transforms, or based on fitting Gaussian
      mixtures directly to the thresholded image data. Pixel replication works
      equivalently on both 2-D and 3-D image data, and naturally combines information
      from multichannel images. The accuracy of the proposed technique is measured
      using both the segmentation accuracy on simulated ellipse data and the tracking
      accuracy on validated stem cell tracking results extracted from hundreds of live
      cell microscopy image sequences. Pixel replication is shown to be significantly
      more accurate compared to other approaches. Variance relationships are derived,
      allowing a more practically effective Gaussian mixture model to extract cell
      boundaries for data generated from the threshold image using the uniform
      elliptical distribution and from the distance transform image using the
      triangular elliptical distribution.

PMID- 30296217
TI  - Local Phase Velocity Based Imaging (LPVI): A New Technique Used For Ultrasound
      Shear Wave Elastography.
AB  - Ultrasound shear wave elastography is an imaging modality for noninvasive
      evaluation of tissue mechanical properties. However, many current techniques
      overestimate lesions dimension or shape especially when small inclusions are
      taken into account. In this study we propose a new method called local phase
      velocity based imaging (LPVI) as an alternative technique to measure tissue
      elasticity. Two separate acquisitions with ultrasound push beams focused once on
      the left side and once on the right side of the inclusion were generated. A local
      shear wave velocity is then recovered in the frequency domain (for a single
      frequency or frequency band) for both acquired data sets. Finally, a two
      dimensional shear wave velocity map is reconstructed by combining maps from two
      separate acquisitions. Robust and accurate shear wave velocity maps are
      reconstructed using the proposed LPVI method in calibrated liver fibrosis tissue
      mimicking homogeneous phantoms, a calibrated elastography phantom with stepped
      cylinder inclusions and a homemade gelatin phantom with ex vivo porcine liver
      inclusion. Results are compared with an existing phase velocity based imaging
      approach and a group velocity based method considered as the state-of-the-art.
      Results from the phantom study showed that increased frequency improved the shape
      of the reconstructed inclusions and contrast-to-noise ratio between the target
      and background.

PMID- 30296218
TI  - Fully-differential Piezoelectric Button-like Mode Disk Resonator for Liquid Phase
      Sensing.
AB  - We present a unique lateral shear resonance mode excited in a micro-electro
      mechanical (MEM) disk resonator. We refer to this proposed mode as the Button
      like (BL) mode. The BL mode has a characteristic lateral strain profile (based on
      the sum of orthogonal strain components in the plane of fabrication) resembles a
      shirt button. Hence our choice of name for this mode. The strain profile of the
      BL mode is highly suited for piezoelectric transduction. Like the more widely
      reported Wine Glass (WG) or elliptical mode, the BL mode offers feedthrough
      cancellation through fully-differential transduction. But compared to the WG
      mode, the BL mode possesses higher coupling coefficient (keff2) and higher
      quality (Q) factor for the same disk radius. These advantages make the BL mode
      highly-attractive for realizing electrically-addressed MEM resonators for liquid
      phase sensing. This paper examines various design aspects pertaining to the BL
      mode: tether geometry, characterization setup, size of disk, and even the effect
      of the gap around the disk on Q factor. The highest Q factor measured in water is
      410 based on a disk with a radius of 150 MUm. The lowest motional resistance in
      water is 1.36 kOmega based on a disk with a radius of 400 MUm.

PMID- 30296219
TI  - Dictionary Representations for Electrode Displacement Elastography.
AB  - Ultrasound electrode displacement elastography (EDE) has demonstrated the
      potential to monitor ablated regions in human patients after minimally invasive
      microwave ablation procedures. Displacement estimation for EDE is commonly
      plagued by decorrelation noise artifacts degrading displacement estimates. In
      this paper we propose a global dictionary learning approach applied to denoising
      displacement estimates with an adaptively learned dictionary from EDE phantom
      displacement maps. The resulting algorithm is one that represents displacement
      patches sparsely if they contain low noise and averages remaining patches thereby
      denoising displacement maps while retaining important edge information. Results
      of dictionary represented displacements presented with higher signal-to-noise
      ratio (SNR), contrast-to-noise ratio (CNR) with improved contrast, as well as
      improved phantom inclusion delineation when compared to initial displacements,
      median filtered displacements, and spline smoothened displacements respectively.
      In addition to visualized noise reduction, dictionary represented displacements
      presented with the highest SNR, CNR and improved contrast with values of 1.77 dB,
      4.56 dB, and 4.35 dB when compared to axial strain tensor images estimated using
      the initial displacements. Following EDE phantom imaging, we utilized dictionary
      representations from in-vivo patient data, further validating efficacy. Denoising
      displacement estimates is a newer application for dictionary learning producing
      strong ablated region delineation with little degradation from denoising.

PMID- 30296220
TI  - Sparse Convolutional Beamforming for Ultrasound Imaging.
AB  - The standard technique used by commercial medical ultrasound systems to form B
      mode images is delay and sum (DAS) beamforming. However, DAS often results in
      limited image resolution and contrast, which are governed by the center frequency
      and the aperture size of the ultrasound transducer. A large number of elements
      leads to improved resolution but at the same time increases the data size and the
      system cost due to the receive electronics required for each element. Therefore,
      reducing the number of receiving channels while producing high quality images is
      of great importance. In this paper, we introduce a nonlinear beamformer called
      COnvolutional Beamforming Algorithm (COBA), which achieves significant
      improvement of lateral resolution and contrast. In addition, it can be
      implemented efficiently using the fast Fourier transform. Based on the COBA
      concept, we next present two sparse beamformers with closed form expressions for
      the sensor locations, which result in the same beam pattern as DAS and COBA while
      using far fewer array elements. Optimization of the number of elements shows that
      they require a minimal number of elements which is on the order of the square
      root of the number used by DAS. The performance of the proposed methods is tested
      and validated using simulated data, phantom scans and in vivo cardiac data. The
      results demonstrate that COBA outperforms DAS in terms of resolution and contrast
      and that the suggested beamformers offer a sizable element reduction while
      generating images with an equivalent or improved quality in comparison to DAS.

PMID- 30296221
TI  - Broadband 1-3 Piezoelectric Composite Transducer Design using Sierpinski Gasket
      Fractal Geometry.
AB  - Wider operational bandwidth is an important requirement of an ultrasound
      transducer across many applications. In nature, it can be observed that several
      hearing organs possess a broad operating bandwidth by having a varying length
      scales structure. Moreover, conventional 1-3 piezoelectric composite transducers
      have been widely recognized for their wider bandwidth over their piezoelectric
      ceramic counterparts. In this paper, a novel 1-3 piezoelectric composite design
      using a fractal geometry, known as the Sierpinski Gasket (SG), is proposed in
      order to explore the potential of further extending the operational bandwidth and
      sensitivity of the transducer. Two equivalent 1-3 piezocomposite designs are
      compared to this end, one with a conventional periodic parallelepiped shaped
      pillar structure and one with the SG fractal geometry, both theoretically, using
      a finite element (FE) analysis package, and experimentally. The transmit voltage
      response and open circuit voltage response are used to illustrate bandwidth
      improvement from the fractal composite design. Following the simulation results,
      a 580 kHz single element transducer, utilizing the proposed SG fractal
      microstructure, is fabricated using a pillar placement methodology. The
      performance of the prototyped device is characterized and compared with a
      conventional 1-3 composite design, as well as with a commercial ultrasound
      transducer. In the one-way transmission mode, a bandwidth improvement of 27.2 %
      and sensitivity enhancement of 3.8 dB can be found with the SG fractal design
      compared to an equivalent conventional composite design and up 105.1 % bandwidth
      improvement when compared to the commercial transducer. In the one-way reception
      mode, the bandwidth improvement for the SG fractal design is 2.5 % and 32.9 %
      when compared to the conventional and commercial transducers, respectively.

PMID- 30296222
TI  - Cs Fountain Clocks for Commercial Realisations - an Improved and Robust Design.
AB  - We report on the design, assembly, testing and delivery of a series of new
      caesium fountain primary frequency standards built through commercial and
      scientific collaboration with international users. The new design, based on
      proven NPL solutions, improves reliability, simplicity of operation and
      transportability. The complete system consists of a novel physics package, a
      specially developed optical package and dedicated electronics for system control.
      We present results showing that despite their simplified and more compact design,
      the new fountains have state-of-the-art performance in terms of signal-to-noise
      ratio and robust long-term operation. With a sufficiently low noise local
      oscillator they are capable of reaching a short-term stability below 3*10-14 (1
      s) and have potential accuracy in the low 10-16 range, similar to the best
      caesium fountains currently in operation. This cost-effective solution could be
      used to increase the availability of accurate frequency references and timescales
      and provide redundancy in critical locations.

PMID- 30296223
TI  - Hierarchical Contextual Refinement Networks for Human Pose Estimation.
AB  - Predicting human pose in the wild is a challenging problem due to high
      flexibility of joints and possible occlusion. Existing approaches generally
      tackle the difficulties either by holistic prediction or multi-stage processing,
      which suffer from poor performance for locating challenging joints or high
      computational cost. In this paper, we propose a new Hierarchical Contextual
      Refinement Network (HCRN) to robustly predict human poses in an efficient manner,
      where human body joints of different complexities are processed at different
      layers in a context hierarchy. Different from existing approaches, our proposed
      model predicts positions of joints from easy to difficult in a single stage
      through effectively exploiting informative contexts provided in the previous
      layer. Such approach offers two appealing advantages over state-of-the-arts: (1)
      more accurate than predicting all the joints together and (2) more efficient than
      multi-stage processing methods. We design a Contextual Refinement Unit (CRU) to
      implement the proposed model, which enables auto-diffusion of joint detection
      results to effectively transfer informative context from easy joints to difficult
      ones. In this way, difficult joints can be reliably detected even in presence of
      occlusion or severe distracting factors. Multiple CRUs are organized into a tree
      structured hierarchy which is end-to-end trainable and does not require
      processing joints for multiple iterations. Comprehensive experiments evaluate the
      efficacy and efficiency of the proposed HCRN model to improve well-established
      baselines and achieve new state-of-the-art on multiple human pose estimation
      benchmarks.

PMID- 30296224
TI  - Joint Tumor Segmentation in PET-CT Images Using Co-Clustering and Fusion Based on
      Belief Functions.
AB  - Precise delineation of target tumor is a key factor to ensure the effectiveness
      of radiation therapy. While hybrid positron emission tomography-computed
      tomography (PET-CT) has become a standard imaging tool in the practice of
      radiation oncology, many existing automatic/semi-automatic methods still perform
      tumor segmentation on mono-modal images. In this paper, a co-clustering algorithm
      is proposed to concurrently segment 3D tumors in PET-CT images, considering that
      the two complementary imaging modalities can combine functional and anatomical
      information to improve segmentation performance. The theory of belief functions
      is adopted in the proposed method to model, fuse, and reason with uncertain and
      imprecise knowledge from noisy and blurry PET-CT images. To ensure reliable
      segmentation for each modality, the distance metric for the quantification of
      clustering distortions and spatial smoothness is iteratively adapted during the
      clustering procedure. On the other hand, to encourage consistent segmentation
      between different modalities, a specific context term is proposed in the
      clustering objective function. Moreover, during the iterative optimization
      process, clustering results for the two distinct modalities are further adjusted
      via a belief-functions-based information fusion strategy. The proposed method has
      been evaluated on a data set consisting of 21 paired PET-CT images for non-small
      cell lung cancer patients. The quantitative and qualitative evaluations show that
      our proposed method performs well compared with the state-of-the-art methods.

PMID- 30296225
TI  - Deep Crisp Boundaries: From Boundaries to Higher-Level Tasks.
AB  - Edge detection has made significant progress with the help of deep convolutional
      networks (ConvNet). These ConvNet-based edge detectors have approached human
      level performance on standard benchmarks. We provide a systematical study of
      these detectors' outputs. We show that the detection results did not accurately
      localize edge pixels, which can be adversarial for tasks that require crisp edge
      inputs. As a remedy, we propose a novel refinement architecture to address the
      challenging problem of learning a crisp edge detector using ConvNet. Our method
      leverages a top-down backward refinement pathway, and progressively increases the
      resolution of feature maps to generate crisp edges. Our results achieve superior
      performance, surpassing human accuracy when using standard criteria on BSDS500,
      and largely outperforming the state-of-the-art methods when using more strict
      criteria. More importantly, we demonstrate the benefit of crisp edge maps for
      several important applications in computer vision, including optical flow
      estimation, object proposal generation, and semantic segmentation.

PMID- 30296226
TI  - Minimal Paths for Tubular Structure Segmentation With Coherence Penalty and
      Adaptive Anisotropy.
AB  - The minimal path method has proven to be particularly useful and efficient in
      tubular structure segmentation applications. In this paper, we propose a new
      minimal path model associated with a dynamic Riemannian metric embedded with an
      appearance feature coherence penalty and an adaptive anisotropy enhancement term.
      The features that characterize the appearance and anisotropy properties of a
      tubular structure are extracted through the associated orientation score. The
      proposed the dynamic Riemannian metric is updated in the course of the geodesic
      distance computation carried out by the efficient single-pass fast marching
      method. Compared to the state-of-the-art minimal path models, the proposed
      minimal path model is able to extract the desired tubular structures from a
      complicated vessel tree structure. In addition, we propose an efficient prior
      path-based method to search for vessel radius value at each centerline position
      of the target. Finally, we perform the numerical experiments on both synthetic
      and real images. The quantitive validation is carried out on retinal vessel
      images. The results indicate that the proposed model indeed achieves a promising
      performance.

PMID- 30296227
TI  - Fine-Grained Quality Assessment for Compressed Images.
AB  - Image quality assessment (IQA) has attracted more and more attention due to the
      urgent demand in image services. The perceptual-based image compression is one of
      the most prominent applications that require IQA metrics to be highly correlated
      with human vision. To explore IQA algorithms that are more consistent with human
      vision, several calibrated databases have been constructed. However, the
      distorted images in the existing databases are usually generated by corrupting
      the pristine images with various distortions in coarse levels, such that the IQA
      algorithms validated on them may be inefficient to optimize the perceptual-based
      image compression with fine-grained quality differences. In this paper, we
      construct a large-scale image database which can be used for fine-grained quality
      assessment of compressed images. In the proposed database, reference images are
      compressed at constant bitrate levels by JPEG encoders with different
      optimization methods. To distinguish subtle differences, the pair-wise comparison
      method is utilized to rank them in subjective experiments. We select 100
      reference images for the proposed database, and each image is compressed into
      three target bitrates by four different JPEG optimization methods, such that 1200
      distorted images are generated in total. Sixteen well-known IQA algorithms are
      evaluated and analyzed on the proposed database. With the devised fine-grained
      IQA database, we expect to further promote image quality assessment by shifting
      it from a coarse-grained stage to a fine-grained stage. The database is available
      at: https://sites.google.com/site/zhangxinf07/fg-iqa.

PMID- 30296228
TI  - High-quality Image Restoration Using Low-Rank Patch Regularization and Global
      Structure Sparsity.
AB  - In recent years, approaches based on nonlocal self similarity and global
      structure regularization have led to significant improvements in image
      restoration. Nonlocal self similarity exploits the repetitiveness of small image
      patches as a powerful prior in the reconstruction process. Likewise, global
      structure regularization is based on the principle that the structure of objects
      in the image is represented by a relatively small portion of pixels. Enforcing
      this structural information to be sparse can thus reduce the occurrence of
      reconstruction artifacts. So far, most image restoration approaches have
      considered one of these two strategies, but not both. This paper presents a novel
      image restoration method that combines nonlocal self similarity and global
      structure sparsity in a single efficient model. Group of similar patches are
      reconstructed simultaneously, via an adaptive regularization technique based on
      the weighted nuclear norm. Moreover, global structure is preserved using an
      innovative strategy, which decomposes the image into a smooth component and a
      sparse residual, the latter regularized using l1 norm. An optimization technique,
      based on the Alternating Direction Method of Multipliers (ADMM) algorithm, is
      used to recover corrupted images efficiently. The performance of the proposed
      method is evaluated on two important image restoration tasks: image completion
      and super-resolution. Experimental results show our method to outperform state-of
      the-art approaches for these tasks, for various types and levels of image
      corruption.

PMID- 30296229
TI  - Deep Color Guided Coarse-to-Fine Convolutional Network Cascade for Depth Image
      Super-Resolution.
AB  - Depth image super-resolution is a significant yet challenging task. In this
      paper, we introduce a novel deep color guided coarse-to-fine convolutional neural
      network (CNN) framework to address this problem. First, we present a datadriven
      filter method to approximate the ideal filter for depth image super-resolution
      instead of hand-designed filters. Based on large data samples, the filter learned
      is more accurate and stable for upsampling depth image. Second, we introduce a
      coarse-to-fine CNN to learn different sizes of filter kernels. In coarse stage,
      larger filter kernels are learned by CNN to achieve crude high-resolution depth
      image. As to fine stage, the crude high-resolution depth image is used as the
      input so that smaller filter kernels are learned to gain more accurate results.
      Benefit from this network, we can progressively recover the high frequency
      details. Third, we construct a color guidance strategy that fuses color
      difference and spatial distance for depth image upsampling. We revise the
      interpolated high-resolution depth image according to the corresponding pixels in
      highresolution color maps. Guided by color information, the depth of high
      resolution image obtained can alleviate texture copying artifacts and preserve
      edge details effectively. Quantitative and qualitative experimental results
      demonstrate our state-of-the-art performance for depth map super-resolution.

PMID- 30296230
TI  - Unifying Sum and Weighted Aggregations for Efficient yet Effective Image
      Representation Computation.
AB  - Embedding and aggregating a set of local descriptors (e.g. SIFT) into a single
      vector is normally used to represent images in image search. Standard aggregation
      operations include sum and weighted aggregations. While showing high efficiency,
      sum aggregation lacks discriminative power. In contrast, weighted aggregation
      shows promising retrieval performance but suffers extremely high time cost. In
      this work, we present a general mixed aggregation method that unifies sum and
      weighted aggregation methods. Owing to its general formulation, our method is
      able to balance the trade-off between retrieval quality and image representation
      efficiency. Additionally, to improve query performance, we propose computing
      multiple weighting coefficients rather than one for each to be aggregated vector
      by partitioning them into several components with negligible computational cost.
      Extensive experimental results on standard public image retrieval benchmarks
      demonstrate that our aggregation method achieves state-of-the-art performance
      while showing over ten times speedup over baselines.

PMID- 30296231
TI  - Moving Object Detection in Complex Scene Using Spatiotemporal Structured-Sparse
      RPCA.
AB  - Moving object detection is a fundamental step in various computer vision
      applications. Robust Principal Component Analysis (RPCA) based methods have often
      been employed for this task. However, the performance of these methods
      deteriorates in the presence of dynamic background scenes, camera jitter,
      camouflaged moving objects, and/or variations in illumination. It is because of
      an underlying assumption that the elements in the sparse component are mutually
      independent, and thus the spatiotemporal structure of the moving objects is lost.
      To address this issue, we propose a spatiotemporal structured sparse RPCA
      algorithm for moving objects detection, where we impose spatial and temporal
      regularization on the sparse component in the form of graph Laplacians. Each
      Laplacian corresponds to a multi-feature graph constructed over superpixels in
      the input matrix. We enforce the sparse component to act as eigenvectors of the
      spatial and temporal graph Laplacians while minimizing the RPCA objective
      function. These constraints incorporate a spatiotemporal subspace structure
      within the sparse component. Thus, we obtain a novel objective function for
      separating moving objects in the presence of complex backgrounds. The proposed
      objective function is solved using a linearized alternating direction method of
      multipliers based batch optimization. Moreover, we also propose an online
      optimization algorithm for real-time applications. We evaluated both the batch
      and online solutions using six publicly available datasets that included most of
      the aforementioned challenges. Our experiments demonstrated the superior
      performance of the proposed algorithms compared with the current state-of-the-art
      methods.

PMID- 30296232
TI  - Blind deblurring of natural stochastic textures using an anisotropic fractal
      model and phase retrieval algorithm.
AB  - The challenging inverse problem of blind deblurring has been investigated
      thoroughly for natural images. Existing algorithms exploit edge-type structures,
      or similarity to smaller patches within the image, to estimate the correct
      blurring kernel. However, these methods do not perform well enough on natural
      stochastic textures (NST), which are mostly random and in general are not
      characterized by distinct edges and contours. In NST even small kernels cause
      severe degradation to images. Restoration poses therefore an outstanding
      challenge. In this work, we refine an existing method by implementing an
      anisotropic fractal model to estimate the blur kernel's power spectral density.
      The final kernel is then estimated via an adaptation of a phase retrieval
      algorithm, originally proposed for sparse signals. We further incorporate
      additional constraints that are specific to blur filters, to yield even better
      results. The latter are compared with results obtained by recently published
      blind deblurring methods.

PMID- 30296233
TI  - CamStyle: A Novel Data Augmentation Method for Person Re-Identification.
AB  - Person re-identification (re-ID) is a cross-camera retrieval task that suffers
      from image style variations caused by different cameras. The art implicitly
      addresses this problem by learning a camera-invariant descriptor subspace. In
      this paper, we explicitly consider this challenge by introducing camera style
      (CamStyle). CamStyle can serve as a data augmentation approach that reduces the
      risk of deep network overfitting and that smooths the CamStyle disparities.
      Specifically, with a style transfer model, labeled training images can be style
      transferred to each camera, and along with the original training samples, form
      the augmented training set. This method, while increasing data diversity against
      overfitting, also incurs a considerable level of noise. In the effort to
      alleviate the impact of noise, the label smooth regularization (LSR) is adopted.
      The vanilla version of our method (without LSR) performs reasonably well on few
      camera systems in which overfitting often occurs. With LSR, we demonstrate
      consistent improvement in all systems regardless of the extent of overfitting. We
      also report competitive accuracy compared with the state of the art on Market
      1501 and DukeMTMC-re-ID. Importantly, CamStyle can be employed to the challenging
      problems of one view learning and unsupervised domain adaptation (UDA) in person
      re-identification (re-ID), both of which have critical research and application
      significance. The former only has labeled data in one camera view and the latter
      only has labeled data in the source domain. Experimental results show that
      CamStyle significantly improves the performance of the baseline in the two
      problems. Specially, for UDA, CamStyle achieves state-of-the-art accuracy based
      on a baseline deep re-ID model on Market-1501 and DukeMTMC-reID. Our code is
      available at: https://github.com/zhunzhong07/CamStyle .

PMID- 30296234
TI  - Improving the Visual Quality of Size-Invariant Visual Cryptography for Grayscale
      Images: An Analysis-by-Synthesis (AbS) Approach.
AB  - In visual cryptography (VC) for grayscale image, size reduction leads to bad
      perceptual quality to the reconstructed secret image. To improve the quality, the
      current efforts are limited to the design of VC algorithm for binary image, and
      measuring the quality with metrics that are not directly related to how the human
      visual system (HVS) perceives halftone images. We propose an analysis-by
      synthesis (AbS) framework to integrate the halftoning process and the VC
      encoding: the secret pixel/block is reconstructed from the shares in the encoder
      and the error between the reconstructed secret and the original secret images is
      fed back and compensated concurrently by the error diffusion process. In doing
      so, the error between the reconstructed secret and original secret is pushed to
      high frequency band, thus producing visually pleasing reconstructed secret image.
      This framework is simple and flexible in that it can be combined with many
      existing size-invariant VC algorithms, including probabilistic VC, random grid VC
      and vector/block VC. More importantly, it is proved that this AbS framework is as
      secure as the traditional VC algorithms. Experimental results demonstrate the
      effectiveness of the proposed AbS framework.

PMID- 30296235
TI  - Multi-pseudo Regularized Label for Generated Data in Person Re-Identification.
AB  - Sufficient training data normally is required to train deeply learned models.
      However, due to the expensive manual process for labelling large number of images
      (i.e., annotation), the amount of available training data (i.e., real data) is
      always limited. To produce more data for training a deep network, Generative
      Adversarial Network (GAN) can be used to generate artificial sample data (i.e.,
      generated data). However, the generated data usually does not have annotation
      labels. To solve this problem, in this paper, we propose a virtual label called
      Multi-pseudo Regularized Label (MpRL) and assign it to the generated data. With
      MpRL, the generated data will be used as the supplementary of real training data
      to train a deep neural network in a semi-supervised learning fashion. To build
      the corresponding relationship between the real data and generated data, MpRL
      assigns each generated data a proper virtual label which reflects the likelihood
      of the affiliation of the generated data to predefined training classes in the
      real data domain. Unlike the traditional label which usually is a single integral
      number, the virtual label proposed in this work is a set of weight-based values
      each individual of which is a number in (0,1] called multi-pseudo label and
      reflects the degree of relation between each generated data to every pre-defined
      class of real data. A comprehensive evaluation is carried out by adopting two
      state-of-the-art convolutional neural networks (CNNs) in our experiments to
      verify the effectiveness of MpRL. Experiments demonstrate that by assigning MpRL
      to generated data, we can further improve the person re-ID performance on five re
      ID datasets, i.e., Market-1501, DukeMTMC-reID, CUHK03, VIPeR, and CUHK01. The
      proposed method obtains +6.29%, +6.30%, +5.58%, +5.84%, and +3.48% improvements
      in rank-1 accuracy over a strong CNN baseline on the five datasets respectively,
      and outperforms state-of-the-art methods.

PMID- 30296236
TI  - Large-Scale Circuitry Interactions Upon Earthquake Experiences Revealed by
      Recurrent Neural Networks.
AB  - Brain dynamics has recently received increasing interest due to its significant
      importance in basic and clinical neurosciences. However, due to inherent
      difficulties in both data acquisition and data analysis methods, studies on large
      scale brain dynamics of mouse with local field potential (LFP) recording are very
      rare. In this paper, we did a series of works on modeling large-scale mouse brain
      dynamic activities responding to fearful earthquake. Based on LFP recording data
      from 13 brain regions that are closely related to fear learning and memory and
      the effective Bayesian connectivity change point model, we divided the response
      time series into four stages: "Before," "Earthquake," "Recovery," and "After." We
      first reported the changes in power and theta-gamma coupling during stage
      transitions. Then, a recurrent neural network model was designed to model the
      functional dynamics in these thirteen brain regions and six frequency bands in
      response to the fear stimulus. Interestingly, our results showed that the
      functional brain connectivities in theta and gamma bands exhibited distinct
      response processes: in theta band, there is a separated-united-separated
      alternation in whole-brain connectivity and a low-high-low change in connectivity
      strength; however, gamma bands have a united-separated-united transition and a
      high-low-high alternation in connectivity pattern and strength. In general, our
      results offer a novel perspective in studying functional brain dynamics under
      fearful stimulus and reveal its relationship to the brain's structural
      connectivity substrates.

PMID- 30296237
TI  - Kernel Generalized Likelihood Ratio Test for Fault Detection of Biological
      Systems.
AB  - In this paper, we develop an improved fault detection (FD) technique in order to
      enhance the monitoring abilities of nonlinear biological processes. Generalized
      likelihood ratio test (GLRT)-based kernel principal component analysis (KPCA)
      (called also kernel GLRT) is an effective data-driven technique for monitoring
      nonlinear processes. However, it is well known that the data collected from
      complex and multivariate processes are multiscale due to the variety of changes
      that could occur in process with different localization in time and frequency.
      Thus, to enhance the process monitoring abilities, we propose to combine the
      advantages of kernel GLRT and multiscale representation using wavelets by
      developing a multiscale kernel GLRT (MS-KGLRT) detection chart. The proposed
      fault detection approach is addressed so that the KPCA is used to compute the
      model in the feature space and the MS-KGLRT chart is applied to detect the
      faults. The detection performance of the new chart is studied using two examples,
      one using synthetic data and the other using biological process representing a
      Cad System in E. Coli (CSEC) model for detecting small and moderate shifts
      (offset or bias and drift). The MS-KGLRT chart is used to enhance fault detection
      of the CSEC model through monitoring some of the key variables involved in this
      model such as enzymes, lysine, and cadaverine.

PMID- 30296238
TI  - Term-based Personalization for Feature Selection in Clinical Handover Form Auto
      filling.
AB  - Feature learning and selection have been widely applied in many research areas
      because of their good performance and lower complexity. Traditional methods
      usually treat all terms with same feature sets, such that performance can be
      damaged when noisy information is brought by wrong features for a given term. In
      this paper, we propose a term-based personalization approach to finding the best
      features for each term. First, features are given as the input so that we focus
      on selection strategies. Second, we present a feature searching method to
      generate feature candidate subsets for each term. After that, the importance of
      each candidate feature subset to a given term is evaluated by the term-feature
      probabilistic relevance model. Finally, we obtain the personalized feature set
      for each term as a subset of all features. Experiments have been conducted on the
      NICTA Synthetic Nursing Handover dataset and the results show that our approach
      is promising and effective.

PMID- 30296239
TI  - Identifying Key Genes of Liver Cancer by Networking of Multiple Data Sets.
AB  - Liver cancer is one of the deadliest cancers in the world. To find effective
      therapies for this cancer, it is indispensable to identify key genes, which may
      play critical roles in the incidence of the liver cancer. To identify key genes
      of the liver cancer with high accuracy, we integrated multiple microarray gene
      expression data sets to compute common differentially expressed genes, which will
      result more accurate than those from individual data set. To find the main
      functions or pathways that these genes are involved in, some enrichment analyses
      were performed including functional enrichment analysis, pathway enrichment
      analysis, and disease association study. Based on these genes, a protein-protein
      interaction network was constructed and analyzed to identify key genes of the
      liver cancer by combining the local and global influence of nodes in the network.
      The identified key genes, such as TOP2A, ESR1, and KMO, have been demonstrated to
      be key biomarkers of the liver cancer in many publications. All the results
      suggest that our method can effectively identify key genes of the liver cancer.
      Moreover, our method can be applied to other types of data sets to select key
      genes of other complex diseases.

PMID- 30296240
TI  - Combining High Speed ELM Learning with a Deep Convolutional Neural Network
      Feature Encoding for Predicting Protein-RNA Interactions.
AB  - Emerging evidence has shown that RNA plays a crucial role in many cellular
      processes, and their biological functions are primarily achieved by binding with
      a variety of proteins. High-throughput biological experiments provide a lot of
      valuable information for the initial identification of RNA-protein interactions
      (RPIs), but with the increasing complexity of RPIs networks, this method
      gradually falls into expensive and time-consuming situations. Therefore, there is
      an urgent need for high speed and reliable methods to predict RNA-protein
      interactions. In this study, we propose a computational method for predicting the
      RNA-protein interactions using sequence information. The deep learning
      convolution neural network (CNN) algorithm is utilized to mine the hidden high
      level discriminative features from the RNA and protein sequences and feed it into
      the extreme learning machine (ELM) classifier. The experimental results with 5
      fold cross-validation indicate that the proposed method achieves superior
      performance on benchmark datasets (RPI1807, RPI2241 and RPI369) with the accuracy
      of 98.83%, 90.83% and 85.63%, respectively. We further evaluate the performance
      of the proposed model by comparing it with the state-of-the-art SVM classifier
      and other existing methods on the same benchmark data set. The experimental
      results show our model can serve as a useful tool for predicting RNA-protein
      interactions.

PMID- 30296241
TI  - Approximate Optimal Distributed Control of Nonlinear Interconnected Systems Using
      Event-Triggered Nonzero-Sum Games.
AB  - In this paper, approximate optimal distributed control schemes for a class of
      nonlinear interconnected systems with strong interconnections are presented using
      continuous and event-sampled feedback information. The optimal control design is
      formulated as an $N$-player nonzero-sum game where the control policies of the
      subsystems act as players. An approximate Nash equilibrium solution to the game,
      which is the solution to the coupled Hamilton-Jacobi equation, is obtained using
      the approximate dynamic programming-based approach. A critic neural network (NN)
      at each subsystem is utilized to approximate the Nash solution and novel event
      sampling conditions, that are decentralized, are designed to asynchronously
      orchestrate the sampling and transmission of state vector at each subsystem. To
      ensure the local ultimate boundedness of the closed-loop system state and NN
      parameter estimation errors, a hybrid-learning scheme is introduced and the
      stability is guaranteed using Lyapunov-based stability analysis. Finally,
      implementation of the proposed event-based distributed control scheme for linear
      interconnected systems is discussed. For completeness, Zeno-free behavior of the
      event-sampled system is shown analytically and a numerical example is included to
      support the analytical results.

PMID- 30296242
TI  - Output Feedback Q-Learning Control for the Discrete-Time Linear Quadratic
      Regulator Problem.
AB  - Approximate dynamic programming (ADP) and reinforcement learning (RL) have
      emerged as important tools in the design of optimal and adaptive control systems.
      Most of the existing RL and ADP methods make use of full-state feedback, a
      requirement that is often difficult to satisfy in practical applications. As a
      result, output feedback methods are more desirable as they relax this
      requirement. In this paper, we present a new output feedback-based Q-learning
      approach to solving the linear quadratic regulation (LQR) control problem for
      discrete-time systems. The proposed scheme is completely online in nature and
      works without requiring the system dynamics information. More specifically, a new
      representation of the LQR Q-function is developed in terms of the input-output
      data. Based on this new Q-function representation, output feedback LQR
      controllers are designed. We present two output feedback iterative Q-learning
      algorithms based on the policy iteration and the value iteration methods. This
      scheme has the advantage that it does not incur any excitation noise bias, and
      therefore, the need of using discounted cost functions is circumvented, which in
      turn ensures closed-loop stability. It is shown that the proposed algorithms
      converge to the solution of the LQR Riccati equation. A comprehensive simulation
      study is carried out, which illustrates the proposed scheme.

PMID- 30296243
TI  - Multistability of Delayed Hybrid Impulsive Neural Networks With Application to
      Associative Memories.
AB  - The important topic of multistability of continuous- and discrete-time neural
      network (NN) models has been investigated rather extensively. Concerning the
      design of associative memories, multistability of delayed hybrid NNs is studied
      in this paper with an emphasis on the impulse effects. Arising from the spiking
      phenomenon in biological networks, impulsive NNs provide an efficient model for
      synaptic interconnections among neurons. Using state-space decomposition, the
      coexistence of multiple equilibria of hybrid impulsive NNs is analyzed.
      Multistability criteria are then established regrading delayed hybrid impulsive
      neurodynamics, for which both the impulse effects on the convergence rate and the
      basins of attraction of the equilibria are discussed. Illustrative examples are
      given to verify the theoretical results and demonstrate an application to the
      design of associative memories. It is shown by an experimental example that
      delayed hybrid impulsive NNs have the advantages of high storage capacity and
      high fault tolerance when used for associative memories.

PMID- 30296245
TI  - Learning Latent Stable Patterns for Image Understanding With Weak and Noisy
      Labels.
AB  - This paper focuses on weakly supervised image understanding, in which the
      semantic labels are available only at image-level, without the specific object or
      scene location in an image. Existing algorithms implicitly assume that image
      level labels are error-free, which might be too restrictive. In practice, image
      labels obtained from the pretrained predictors are easily contaminated. To solve
      this problem, we propose a novel algorithm for weakly supervised segmentation
      when only noisy image labels are available during training. More specifically, a
      semantic space is constructed first by encoding image labels through a graphlet
      (i.e., superpixel cluster) embedding process. Then, we observe that in the
      semantic space, the distribution of graphlets from images with a same label
      remains stable, regardless of the noises in image labels. Therefore, we propose a
      generative model, called latent stability analysis, to discover the stable
      patterns from images with noisy labels. Inferring graphlet semantics by making
      use of these mid-level stable patterns is much more secure and accurate than
      directly transferring noisy image-level labels into different regions. Finally,
      we calculate the semantics of each superpixel using maximum majority voting of
      its correlated graphlets. Comprehensive experimental results show that our
      algorithm performs impressively when the image labels are predicted by either the
      hand-crafted or deeply learned image descriptors.

PMID- 30296244
TI  - Mining directional drug interaction effects on myopathy using the FAERS database.
AB  - Mining high-order drug-drug interaction (DDI) induced adverse drug effects from
      electronic health record (EHR) databases is an emerging area, and very few
      studies have explored the relationships between high-order drug combinations. We
      investigate a novel pharmacovigilance problem for mining directional DDI effects
      on myopathy using the FDA Adverse Event Reporting System (FAERS) database. Our
      work provides information on the risk of myopathy associated with adding new
      drugs on the already prescribed medication, and visualizes the identified
      directional DDI patterns as user-friendly graphical representation. We utilize
      the Apriori algorithm to extract frequent drug combinations from the FAERS
      database. We use odds ratio (OR) to estimate the risk of myopathy associated with
      directional DDI. We create a tree-structured graph to visualize the findings for
      easy interpretation. Our method confirmed myopathy association with previously
      reported HMG-CoA reductase inhibitors like rosuvastatin, fluvastatin, simvastatin
      and atorvastatin. New, previously unidentified but mechanistically plausible
      associations with myopathy were also observed, such as the DDI between
      pamidronate and levofloxacin. Additional top findings are gadolinium-based
      imaging agents, which however are often used in myopathy diagnosis. Other DDIs
      with no obvious mechanism are also reported, such as that of sulfamethoxazole
      with trimethoprim and potassium chloride. This study shows the feasibility to
      estimate high-order directional DDIs in a fast and accurate manner. The results
      of the analysis could become a useful tool in the specialists' hands through an
      easy-to-understand graphic visualization.

PMID- 30296246
TI  - A Directionally Selective Small Target Motion Detecting Visual Neural Network in
      Cluttered Backgrounds.
AB  - Discriminating targets moving against a cluttered background is a huge challenge,
      let alone detecting a target as small as one or a few pixels and tracking it in
      flight. In the insect's visual system, a class of specific neurons, called small
      target motion detectors (STMDs), have been identified as showing exquisite
      selectivity for small target motion. Some of the STMDs have also demonstrated
      direction selectivity which means these STMDs respond strongly only to their
      preferred motion direction. Direction selectivity is an important property of
      these STMD neurons which could contribute to tracking small targets such as mates
      in flight. However, little has been done on systematically modeling these
      directionally selective STMD neurons. In this paper, we propose a directionally
      selective STMD-based neural network for small target detection in a cluttered
      background. In the proposed neural network, a new correlation mechanism is
      introduced for direction selectivity via correlating signals relayed from two
      pixels. Then, a lateral inhibition mechanism is implemented on the spatial field
      for size selectivity of the STMD neurons. Finally, a population vector algorithm
      is used to encode motion direction of small targets. Extensive experiments showed
      that the proposed neural network not only is in accord with current biological
      findings, i.e., showing directional preferences but also worked reliably in
      detecting the small targets against cluttered backgrounds.

PMID- 30296247
TI  - e-RNSP: An Efficient Method for Mining Repetition Negative Sequential Patterns.
AB  - Negative sequential patterns (NSPs), which capture both frequent occurring and
      nonoccurring behaviors, become increasingly important and sometimes play a role
      irreplaceable by analyzing occurring behaviors only. Repetition sequential
      patterns capture repetitions of patterns in different sequences as well as within
      a sequence and are very important to understand the repetition relations between
      behaviors. Though some methods are available for mining NSP and repetition
      positive sequential patterns (RPSPs), we have not found any methods for mining
      repetition NSP (RNSP). RNSP can help the analysts to further understand the
      repetition relationships between items and capture more comprehensive information
      with repetition properties. However, mining RNSP is much more difficult than
      mining NSP due to the intrinsic challenges of nonoccurring items. To address the
      above issues, we first propose a formal definition of repetition negative
      containment. Then, we propose a method to convert repetition negative containment
      to repetition positive containment, which fast calculates the repetition supports
      by only using the corresponding RPSP's information without rescanning databases.
      Finally, we propose an efficient algorithm, called e-RNSP, to mine RNSP
      efficiently. To the best of our knowledge, e-RNSP is the first algorithm to
      efficiently mine RNSP. Intensive experimental results on the first four real and
      synthetic datasets clearly show that e-RNSP can efficiently discover the
      repetition negative patterns; results on the fifth dataset prove the
      effectiveness of RNSP which are captured by the proposed method; and the results
      on the rest 16 datasets analyze the impacts of data characteristics on mining
      process.

PMID- 30296248
TI  - Objective-Domain Dual Decomposition: An Effective Approach to Optimizing
      Partially Differentiable Objective Functions.
AB  - This paper addresses a class of optimization problems in which either part of the
      objective function is differentiable while the rest is nondifferentiable or the
      objective function is differentiable in only part of the domain. Accordingly, we
      propose a dual-decomposition-based approach that includes both objective
      decomposition and domain decomposition. In the former, the original objective
      function is decomposed into several relatively simple subobjectives to isolate
      the nondifferentiable part of the objective function, and the problem is
      consequently formulated as a multiobjective optimization problem (MOP). In the
      latter decomposition, we decompose the domain into two subdomains, that is, the
      differentiable and nondifferentiable domains, to isolate the nondifferentiable
      domain of the nondifferentiable subobjective. Subsequently, the problem can be
      optimized with different schemes in the different subdomains. We propose a
      population-based optimization algorithm, called the simulated water-stream
      algorithm (SWA), for solving this MOP. The SWA is inspired by the natural
      phenomenon of water streams moving toward a basin, which is analogous to the
      process of searching for the minimal solutions of an optimization problem. The
      proposed SWA combines the deterministic search and heuristic search in a single
      framework. Experiments show that the SWA yields promising results compared with
      its existing counterparts.

PMID- 30296249
TI  - Multiobjective Rule-Based Cooperative Continuous Ant Colony Optimized Fuzzy
      Systems With a Robot Control Application.
AB  - This paper proposes a new rule-based cooperative framework for multiobjective
      evolutionary fuzzy systems (FSs). Based on the framework, a multiobjective rule
      based cooperative continuous ant-colony optimization (MO-RCCACO) algorithm is
      proposed to optimize all of the free parameters in FSs. Instead of optimization
      using a single colony of FSs (solutions), the MO-RCCACO consists of r subcolonies
      of size N cooperatively optimizing an FS that consists of r rules, with a
      subcolony optimizing only a single fuzzy rule. In addition, an auxiliary colony
      is created to store all of the fuzzy rules in the best-so-far N FSs to enhance
      the optimization ability of MO-RCCACO. The performance ranking of different fuzzy
      rules in the same subcolony is performed based on the multiobjective function
      values of their participating FSs by using Pareto nondominated sorting and the
      crowding distance. The MO-RCCACO is applied to find the Pareto-optimal fuzzy
      controllers (FCs) of a mobile robot for wall following with multiple control
      objectives. The optimization ability of the MO-RCCACO is verified through
      comparisons with various multiobjective population-based optimization algorithms
      in the robot wall-following control problem. Experimental results verify the
      effectiveness of the MO-RCCACO-based FCs for the boundary following control of a
      real robot.

PMID- 30296250
TI  - Integrated Fault Estimation and Fault-Tolerant Tracking Control for Lipschitz
      Nonlinear Multiagent Systems.
AB  - An integrated fault estimation (FE) and fault-tolerant tracking control (FTTC)
      strategy is developed for Lipschitz nonlinear multiagent systems subject to
      actuator faults, external disturbance, and uncertainties. First, for each agent,
      a corresponding unknown input observer with reduced/full order is constructed to
      obtain the FE. Then, a state/output feedback FTTC strategy is proposed based on
      the integral sliding-mode technique and adaptive super-twisting algorithm. The
      observer and controller gains are obtained simultaneously via Hinfinity
      optimization with a linear matrix inequality formulation. Finally, the comparison
      simulations are provided to demonstrate the effectiveness of the proposed
      algorithm.

PMID- 30296251
TI  - A Multipopulation-Based Multiobjective Evolutionary Algorithm.
AB  - Multipopulation is an effective optimization component often embedded into
      evolutionary algorithms to solve optimization problems. In this paper, a new
      multipopulation-based multiobjective genetic algorithm (MOGA) is proposed, which
      uses a unique cross-subpopulation migration process inspired by biological
      processes to share information between subpopulations. Then, a Markov model of
      the proposed multipopulation MOGA is derived, the first of its kind, which
      provides an exact mathematical model for each possible population occurring
      simultaneously with multiple objectives. Simulation results of two multiobjective
      test problems with multiple subpopulations justify the derived Markov model, and
      show that the proposed multipopulation method can improve the optimization
      ability of the MOGA. Also, the proposed multipopulation method is applied to
      other multiobjective evolutionary algorithms (MOEAs) for evaluating its
      performance against the IEEE Congress on Evolutionary Computation multiobjective
      benchmarks. The experimental results show that a single-population MOEA can be
      extended to a multipopulation version, while obtaining better optimization
      performance.

PMID- 30296252
TI  - Overexpression of Epidermal Growth Factor Receptor (EGFR) and HER-2 in Bladder
      Carcinoma and Its Association with Patients' Clinical Features.
AB  - BACKGROUND The aim of this study was to determine the expression of EGFR/HER-2
      and investigate their association with patients' clinical features in bladder
      transitional cell carcinoma (BTCC). MATERIAL AND METHODS Immunohistochemistry was
      utilized in our study to explore the expression of EGFR/HER-2 of 56 human bladder
      cancer samples and 10 normal bladder samples. RESULTS EGFR and HER-2 expressions
      were both significantly higher in bladder transitional cell carcinoma (BTCC) than
      that in non-cancer bladder samples; the EGFR positivity rate was 55.4% among BTCC
      samples and 37.5% for HER-2a. A statistically significant correlation was also
      present between the increasing EGFR or HER-2 expression levels and the clinical
      stages, pathologic grades, and tumor recurrence. The expression level of EGFR
      increased along with higher clinical stages and pathologic grades of BTCC, and
      the obviously increased expression of HER-2 was statistically associated with
      clinical stages and tumor recurrence. In addition, the expression level of HER-2
      increased along with the higher clinical stage of BTCC. EGFR expression and HER-2
      levels were positively associated in BTCC samples. CONCLUSIONS Our findings
      demonstrate that high EGFR and HER-2 expressions are dramatically increased in
      the BTCC tissues and are closely related to the clinical stages, pathologic
      grades, and tumor recurrence. Therefore, the evaluation of EGFR and HER-2
      expression in BTCC may contribute to identifying patients who are at increased
      risk of disease progression and recurrence.

PMID- 30296253
TI  - Candida albicans biofilm-induced vesicles confer drug resistance through matrix
      biogenesis.
AB  - Cells from all kingdoms of life produce extracellular vesicles (EVs). Their cargo
      is protected from the environment by the surrounding lipid bilayer. EVs from many
      organisms have been shown to function in cell-cell communication, relaying
      signals that impact metazoan development, microbial quorum sensing, and
      pathogenic host-microbe interactions. Here, we have investigated the production
      and functional activities of EVs in a surface-associated microbial community or
      biofilm of the fungal pathogen Candida albicans. Crowded communities like
      biofilms are a context in which EVs are likely to function. Biofilms are
      noteworthy because they are encased in an extracellular polymeric matrix and
      because biofilm cells exhibit extreme tolerance to antimicrobial compounds. We
      found that biofilm EVs are distinct from those produced by free-living planktonic
      cells and display strong parallels in composition to biofilm matrix material. The
      functions of biofilm EVs were delineated with a panel of mutants defective in
      orthologs of endosomal sorting complexes required for transport (ESCRT) subunits,
      which are required for normal EV production in diverse eukaryotes. Most ESCRT
      defective mutations caused reduced biofilm EV production, reduced matrix
      polysaccharide levels, and greatly increased sensitivity to the antifungal drug
      fluconazole. Matrix accumulation and drug hypersensitivity of ESCRT mutants were
      reversed by addition of wild-type (WT) biofilm EVs. Vesicle complementation
      showed that biofilm EV function derives from specific cargo proteins. Our studies
      indicate that C. albicans biofilm EVs have a pivotal role in matrix production
      and biofilm drug resistance. Biofilm matrix synthesis is a community enterprise;
      prior studies of mixed cell biofilms have demonstrated extracellular
      complementation. Therefore, EVs function not only in cell-cell communication but
      also in the sharing of microbial community resources.

PMID- 30296255
TI  - Single copy/knock-in models of ALS SOD1 in C. elegans suggest loss and gain of
      function have different contributions to cholinergic and glutamatergic
      neurodegeneration.
AB  - Mutations in Cu/Zn superoxide dismutase 1 (SOD1) lead to Amyotrophic Lateral
      Sclerosis (ALS), a neurodegenerative disease that disproportionately affects
      glutamatergic and cholinergic motor neurons. Previous work with SOD1
      overexpression models supports a role for SOD1 toxic gain of function in ALS
      pathogenesis. However, the impact of SOD1 loss of function in ALS cannot be
      directly examined in overexpression models. In addition, overexpression may
      obscure the contribution of SOD1 loss of function in the degeneration of
      different neuronal populations. Here, we report the first single-copy, ALS knock
      in models in C. elegans generated by transposon- or CRISPR/Cas9- mediated genome
      editing of the endogenous sod-1 gene. Introduction of ALS patient amino acid
      changes A4V, H71Y, L84V, G85R or G93A into the C. elegans sod-1 gene yielded
      single-copy/knock-in ALS SOD1 models. These differ from previously reported
      overexpression models in multiple assays. In single-copy/knock-in models, we
      observed differential impact of sod-1 ALS alleles on glutamatergic and
      cholinergic neurodegeneration. A4V, H71Y, G85R, and G93A animals showed increased
      SOD1 protein accumulation and oxidative stress induced degeneration, consistent
      with a toxic gain of function in cholinergic motor neurons. By contrast, H71Y,
      L84V, and G85R lead to glutamatergic neuron degeneration due to sod-1 loss of
      function after oxidative stress. However, dopaminergic and serotonergic neuronal
      populations were spared in single-copy ALS models, suggesting a neuronal-subtype
      specificity previously not reported in invertebrate ALS SOD1 models. Combined,
      these results suggest that knock-in models may reproduce the neurotransmitter
      type specificity of ALS and that both SOD1 loss and gain of toxic function
      differentially contribute to ALS pathogenesis in different neuronal populations.

PMID- 30296254
TI  - Protection induced by a Francisella tularensis subunit vaccine delivered by
      glucan particles.
AB  - Francisella tularensis is an intracellular pathogen causing the disease
      tularemia, and an organism of concern to biodefence. There is no licensed vaccine
      available. Subunit approaches have failed to induce protection, which requires
      both humoral and cellular immune memory responses, and have been hampered by a
      lack of understanding as to which antigens are immunoprotective. We undertook a
      preliminary in silico analysis to identify candidate protein antigens. These
      antigens were then recombinantly expressed and encapsulated into glucan particles
      (GPs), purified Saccharomyces cerevisiae cell walls composed primarily of beta
      1,3-glucans. Immunological profiling in the mouse was used to down-selection to
      seven lead antigens: FTT1043 (Mip), IglC, FTT0814, FTT0438, FTT0071 (GltA),
      FTT0289, FTT0890 (PilA) prior to transitioning their evaluation to a Fischer 344
      rat model for efficacy evaluation. F344 rats were vaccinated with the GP protein
      antigens co-delivered with GP-loaded with Francisella LPS. Measurement of cell
      mediated immune responses and computational epitope analysis allowed down
      selection to three promising candidates: FTT0438, FTT1043 and FTT0814. Of these,
      a GP vaccine delivering Francisella LPS and the FTT0814 protein was able to
      induce protection in rats against an aerosol challenge of F. tularensis SchuS4,
      and reduced organ colonisation and clinical signs below that which immunisation
      with a GP-LPS alone vaccine provided. This is the first report of a protein
      supplementing protection induced by LPS in a Francisella vaccine. This paves the
      way for developing an effective, safe subunit vaccine for the prevention of
      inhalational tularemia, and validates the GP platform for vaccine delivery where
      complex immune responses are required for prevention of infections by
      intracellular pathogens.

PMID- 30296256
TI  - Recombination hotspots in an extended human pseudoautosomal domain predicted from
      double-strand break maps and characterized by sperm-based crossover analysis.
AB  - The human X and Y chromosomes are heteromorphic but share a region of homology at
      the tips of their short arms, pseudoautosomal region 1 (PAR1), that supports
      obligate crossover in male meiosis. Although the boundary between pseudoautosomal
      and sex-specific DNA has traditionally been regarded as conserved among primates,
      it was recently discovered that the boundary position varies among human males,
      due to a translocation of ~110 kb from the X to the Y chromosome that creates an
      extended PAR1 (ePAR). This event has occurred at least twice in human evolution.
      So far, only limited evidence has been presented to suggest this extension is
      recombinationally active. Here, we sought direct proof by examining thousands of
      gametes from each of two ePAR-carrying men, for two subregions chosen on the
      basis of previously published male X-chromosomal meiotic double-strand break
      (DSB) maps. Crossover activity comparable to that seen at autosomal hotspots was
      observed between the X and the ePAR borne on the Y chromosome both at a distal
      and a proximal site within the 110-kb extension. Other hallmarks of classic
      recombination hotspots included evidence of transmission distortion and GC-biased
      gene conversion. We observed good correspondence between the male DSB clusters
      and historical recombination activity of this region in the X chromosomes of
      females, as ascertained from linkage disequilibrium analysis; this suggests that
      this region is similarly primed for crossover in both male and female germlines,
      although sex-specific differences may also exist. Extensive resequencing and
      inference of ePAR haplotypes, placed in the framework of the Y phylogeny as
      ascertained by both Y microsatellites and single nucleotide polymorphisms,
      allowed us to estimate a minimum rate of crossover over the entire ePAR region of
      6-fold greater than genome average, comparable with pedigree estimates of PAR1
      activity generally. We conclude ePAR very likely contributes to the critical
      crossover function of PAR1.

PMID- 30296258
TI  - Examining food intake and eating out of home patterns among university students.
AB  - Eating out of home (OH) is increasingly popular in Balkan countries, among them
      Albania. To date there is only anecdotal evidence regarding nutritional quality
      of food consumed OH and the contribution to diet. This study assessed intake of
      foods and drinks consumed OH and at home (AH), as well as their nutritional
      contribution to the daily diet of university students in Tirana, Albania. Using a
      single day Automated Multiple Pass Method (AMPM) 24-hour dietary recall, we
      examined food intake among 289 students aged 18-24 years old, from three major
      universities in Albania. Contribution of eating OH to total energy intake per
      day, as well as to daily consumption of macronutrients by eating OH intensity
      tertiles were assessed. Foods and drinks consumed OH contributed 46.9%
      [95%CI:41.4-52.8] of total daily energy intake, representing, on average,
      1169.1kcal [95%CI:1088.3-1249.9]. Sweets, soft drinks and meat products were more
      frequently consumed OH, while fruits and vegetables consumption was extremely
      low. The average quantity of sugars and dietary fats per day was higher AH, 76.9g
      [95%CI:70.3-83.5] and 173.7g [95%CI:163.2-184.2] respectively, compared to OH,
      33.7g [95%CI:30.4-37.0] and 142.0g [95%CI:131.5-152.5] respectively. Dietary
      composition of AH intake was richer in sugars, total fats and proteins, while OH
      intake was richer in saturated fats. The overall diet appeared unhealthy, when
      nutrients were assessed as energy percentage against WHO proposed nutrient
      standards for sugar and saturated fats. Eating OH, even though was associated
      with lower fruits and vegetables intake, was not clearly associated with poor
      diet quality, as AH foods were also characterized by increased saturated fats and
      sugars intake as energy percentage. This study provides data on the first
      assessment of current dietary patterns of the studied population and can be used
      as baseline for designing and conducting future studies and interventions
      targeting malnutrition in all its forms.

PMID- 30296257
TI  - The design of schistosomiasis monitoring and evaluation programmes: The
      importance of collecting adult data to inform treatment strategies for
      Schistosoma mansoni.
AB  - Monitoring and evaluation (M&E) programmes are used to collect data which are
      required to assess the impact of current interventions on their progress towards
      achieving the World Health Organization (WHO) goals of morbidity control and
      elimination as a public health problem for schistosomiasis. Prevalence and
      intensity of infection data are typically collected from school-aged children
      (SAC) as they are relatively easy to sample and are thought to be most likely to
      be infected by schistosome parasites. However, adults are also likely to be
      infected. We use three different age-intensity profiles of infection for
      Schistosoma mansoni with low, moderate and high burdens of infection in adults to
      investigate how the age distribution of infection impacts the mathematical model
      generated recommendations of the preventive chemotherapy coverage levels required
      to achieve the WHO goals. We find that for moderate prevalence regions,
      regardless of the burden of infection in adults, treating SAC only may achieve
      the WHO goals. However, for high prevalence regions with a high burden of
      infection in adults, adult treatment is required to meet the WHO goals. Hence, we
      show that the optimal treatment strategy for a defined region requires
      consideration of the burden of infection in adults as it cannot be based solely
      on the prevalence of infection in SAC. Although past epidemiological data have
      informed mathematical models for the transmission and control of schistosome
      infections, more accurate and detailed data are required from M&E programmes to
      accurately determine the optimal treatment strategy for a defined region. We
      highlight the importance of collecting prevalence and intensity of infection data
      from a broader age-range, specifically the inclusion of adult data at baseline
      (prior to treatment) and throughout the treatment programme if possible, rather
      than SAC only, to accurately determine the treatment strategy for a defined
      region. Furthermore, we discuss additional epidemiological data, such as
      individual longitudinal adherence to treatment, that should ideally be collected
      in M&E programmes.

PMID- 30296259
TI  - Identifying a sufficient core group for trachoma transmission.
AB  - BACKGROUND: In many infectious diseases, a core group of individuals plays a
      disproportionate role in transmission. If these individuals were effectively
      prevented from transmitting infection, for example with a perfect vaccine, then
      the disease would disappear in the remainder of the community. No vaccine has yet
      proven effective against the ocular strains of chlamydia that cause trachoma.
      However, repeated treatment with oral azithromycin may be able to prevent
      individuals from effectively transmitting trachoma. METHODOLOGY/PRINCIPAL
      FINDINGS: Here we assess several methods for identifying a core group for
      trachoma, assuming varying degrees of knowledge about the transmission process.
      We determine the minimal core group from a completely specified model, fitted to
      results from a large Ethiopian trial. We compare this benchmark to a core group
      that could actually be identified from information available to trachoma
      programs. For example, determined from the rate of return of infection in a
      community after mass treatments, or from the equilibrium prevalence of infection.
      CONCLUSIONS/SIGNIFICANCE: Sufficient groups are relatively easy for programs to
      identify, but will likely be larger than the theoretical minimum.

PMID- 30296260
TI  - In-silico dynamic analysis of cytotoxic drug administration to solid tumours:
      Effect of binding affinity and vessel permeability.
AB  - The delivery of blood-borne therapeutic agents to solid tumours depends on a
      broad range of biophysical factors. We present a novel multiscale, multiphysics,
      in-silico modelling framework that encompasses dynamic tumour growth,
      angiogenesis and drug delivery, and use this model to simulate the intravenous
      delivery of cytotoxic drugs. The model accounts for chemo-, hapto- and
      mechanotactic vessel sprouting, extracellular matrix remodelling, mechano
      sensitive vascular remodelling and collapse, intra- and extravascular drug
      transport, and tumour regression as an effect of a cytotoxic cancer drug. The
      modelling framework is flexible, allowing the drug properties to be specified,
      which provides realistic predictions of in-vivo vascular development and
      structure at different tumour stages. The model also enables the effects of
      neoadjuvant vascular normalisation to be implicitly tested by decreasing vessel
      wall pore size. We use the model to test the interplay between time of treatment,
      drug affinity rate and the size of the vessels' endothelium pores on the delivery
      and subsequent tumour regression and vessel remodelling. Model predictions
      confirm that small-molecule drug delivery is dominated by diffusive transport and
      further predict that the time of treatment is important for low affinity but not
      high affinity cytotoxic drugs, the size of the vessel wall pores plays an
      important role in the effect of low affinity but not high affinity drugs, that
      high affinity cytotoxic drugs remodel the tumour vasculature providing a large
      window for the normalisation of the vascular architecture, and that the
      combination of large pores and high affinity enhances cytotoxic drug delivery
      efficiency. These results have implications for treatment planning and methods to
      enhance drug delivery, and highlight the importance of in-silico modelling in
      investigating the optimisation of cancer therapy on a personalised setting.

PMID- 30296261
TI  - One size does not fit all: Caste and sex differences in the response of
      bumblebees (Bombus impatiens) to chronic oral neonicotinoid exposure.
AB  - Neonicotinoid insecticides have been implicated in the rapid global decline of
      bumblebees over recent years, particularly in agricultural and urban areas. While
      there is much known about neonicotinoid toxicity effects at the colony stage of
      the bumblebee annual cycle, far less is known about such effects at other stages
      critical for the maintenance of wild populations. In the present work, individual
      based feeding assays were used to show that chronic consumption of the widely
      used neonicotinoid clothianidin at a field-realistic average rate of 3.6 and 4.0
      ng/g.bee/day reduces survival of queen and male bumblebees, respectively, within
      a 7-day period. In contrast, worker survival was unaffected at a similar
      consumption rate of 3.9 ng/g.bee/day. To test the hypothesis that males have a
      lower tolerance for oral clothianidin exposure than workers due to their haploid
      genetic status, RNAseq analysis was used to compare the transcriptomic responses
      of workers and males to chronic intake of clothianidin at a sub-lethal dose of
      0.37ng/bee/day for 5 days. Surprisingly, clothianidin consumption only altered
      the expression of 19 putative detoxification genes in a sex-specific manner, with
      11/19 genes showing increased expression in workers. Sub-lethal clothianidin
      exposure also altered the expression of 40 genes associated with other major
      biological functions, including locomotion, reproduction, and immunity.
      Collectively, these results suggest that chronic oral toxicity effects of
      neonicotinoids are greatest during mating and nest establishment phases of the
      bumblebee life cycle. Chronic oral toxicity testing on males and queens is
      therefore required in order to fully assess the impact of neonicotinoids on wild
      bumblebee populations.

PMID- 30296262
TI  - Interactive reservoir computing for chunking information streams.
AB  - Chunking is the process by which frequently repeated segments of temporal inputs
      are concatenated into single units that are easy to process. Such a process is
      fundamental to time-series analysis in biological and artificial information
      processing systems. The brain efficiently acquires chunks from various
      information streams in an unsupervised manner; however, the underlying mechanisms
      of this process remain elusive. A widely-adopted statistical method for chunking
      consists of predicting frequently repeated contiguous elements in an input
      sequence based on unequal transition probabilities over sequence elements.
      However, recent experimental findings suggest that the brain is unlikely to adopt
      this method, as human subjects can chunk sequences with uniform transition
      probabilities. In this study, we propose a novel conceptual framework to overcome
      this limitation. In this process, neural networks learn to predict dynamical
      response patterns to sequence input rather than to directly learn transition
      patterns. Using a mutually supervising pair of reservoir computing modules, we
      demonstrate how this mechanism works in chunking sequences of letters or visual
      images with variable regularity and complexity. In addition, we demonstrate that
      background noise plays a crucial role in correctly learning chunks in this model.
      In particular, the model can successfully chunk sequences that conventional
      statistical approaches fail to chunk due to uniform transition probabilities. In
      addition, the neural responses of the model exhibit an interesting similarity to
      those of the basal ganglia observed after motor habit formation.

PMID- 30296264
TI  - The effect of assortative mixing on stability of low helminth transmission levels
      and on the impact of mass drug administration: Model explorations for
      onchocerciasis.
AB  - BACKGROUND: Stable low pre-control prevalences of helminth infection are not
      uncommon in field settings, yet it is poorly understood how such low levels can
      be sustained, thereby challenging efforts to model them. Disentangling possible
      facilitating mechanisms is important, since these may differently affect
      intervention impact. Here we explore the role of assortative (i.e. non
      homogenous) mixing and exposure heterogeneity in helminth transmission, using
      onchocerciasis as an example. METHODOLOGY/PRINCIPAL FINDINGS: We extended the
      established individual-based model ONCHOSIM to allow for assortative mixing,
      assuming that individuals who are relatively more exposed to fly bites are more
      connected to each other than other individuals in the population as a result of
      differential exposure to a sub-population of blackflies. We used the model to
      investigate how transmission stability, equilibrium microfilarial (mf) prevalence
      and intensity, and impact of mass drug administration depend on the assumed
      degree of assortative mixing and exposure heterogeneity, for a typical rural
      population of about 400 individuals. The model clearly demonstrated that with
      homogeneous mixing and moderate levels of exposure heterogeneity, onchocerciasis
      could not be sustained below 35% mf prevalence. In contrast, assortative mixing
      stabilised onchocerciasis prevalence at levels as low as 8% mf prevalence.
      Increasing levels of assortative mixing significantly reduced the probability of
      interrupting transmission, given the same duration and coverage of mass drug
      administration. CONCLUSIONS/SIGNIFICANCE: Assortative mixing patterns are an
      important factor to explain stable low prevalence situations and are highly
      relevant for prospects of elimination. Their effect on the pre-control
      distribution of mf intensities in human populations is only detectable in
      settings with mf prevalences <30%, where high skin mf density in mf-positive
      people may be an indication of assortative mixing. Local spatial variation in
      larval infection intensity in the blackfly intermediate host may also be an
      indicator of assortative mixing.

PMID- 30296263
TI  - Noncoding RNA Ginir functions as an oncogene by associating with centrosomal
      proteins.
AB  - Long noncoding RNAs constitute a major fraction of the eukaryotic transcriptome,
      and together with proteins, they intricately fine-tune various growth regulatory
      signals to control cellular homeostasis. Here, we describe the functional
      characterisation of a novel pair of long intergenic noncoding RNAs (lincRNAs)
      comprised of complementary, fully overlapping sense and antisense transcripts
      Genomic Instability Inducing RNA (Ginir) and antisense RNA of Ginir (Giniras),
      respectively, from mouse cells. This transcript pair is expressed in a
      spatiotemporal manner during embryonic development. The individual levels of the
      sense and antisense transcripts are finely balanced during embryonic growth and
      in adult tissues. Functional studies of the individual transcripts performed
      using overexpression and knock-down strategies in mouse cells has led to the
      discovery that Ginir RNA is a regulator of cellular proliferation and can act as
      an oncogene having a preeminent role in malignant transformation.
      Mechanistically, we demonstrate that the oncogenic function of Ginir is mediated
      by its interaction with centrosomal protein 112 (Cep112). Additionally, we
      establish here a specific interaction between Cep112 with breast cancer type 1
      susceptibility protein (Brca1), another centrosome-associated protein. Next, we
      prove that the mutual interaction between Cep112 with Brca1 is significant for
      mitotic regulation and maintenance of genomic stability. Furthermore, we
      demonstrate that the Cep112 protein interaction with Brca1 protein is impaired
      when an elevated level of Ginir RNA is present in the cells, resulting in severe
      deregulation and abnormality in mitosis, leading to malignant transformation.
      Inhibiting the Ginir RNA function in transformed cells attenuates transformation
      and restores genomic stability. Together, these findings unravel, to our
      knowledge, a hitherto-unknown mechanism of oncogenesis mediated by a long
      noncoding RNA and establishes a unique role of Cep112-Brca1 interaction being
      modulated by Ginir RNA in maintaining mitotic fidelity.

PMID- 30296265
TI  - Quantifying how constraints limit the diversity of viable routes to adaptation.
AB  - Convergent adaptation occurs at the genome scale when independently evolving
      lineages use the same genes to respond to similar selection pressures. These
      patterns of genetic repeatability provide insights into the factors that
      facilitate or constrain the diversity of genetic responses that contribute to
      adaptive evolution. A first step in studying such factors is to quantify the
      observed amount of repeatability relative to expectations under a null
      hypothesis. Here, we formulate a novel index to quantify the constraints driving
      the observed amount of repeated adaptation in pairwise contrasts based on the
      hypergeometric distribution, and then generalize this for simultaneous analysis
      of multiple lineages. This index is explicitly based on the probability of
      observing a given amount of repeatability by chance under a given null hypothesis
      and is readily compared among different species and types of trait. We also
      formulate an index to quantify the effective proportion of genes in the genome
      that have the potential to contribute to adaptation. As an example of how these
      indices can be used to draw inferences, we assess the amount of repeatability
      observed in existing datasets on adaptation to stress in yeast and climate in
      conifers. This approach provides a method to test a wide range of hypotheses
      about how different kinds of factors can facilitate or constrain the diversity of
      genetic responses observed during adaptive evolution.

PMID- 30296266
TI  - Quantifying the value of surveillance data for improving model predictions of
      lymphatic filariasis elimination.
AB  - BACKGROUND: Mathematical models are increasingly being used to evaluate
      strategies aiming to achieve the control or elimination of parasitic diseases.
      Recently, owing to growing realization that process-oriented models are useful
      for ecological forecasts only if the biological processes are well defined,
      attention has focused on data assimilation as a means to improve the predictive
      performance of these models. METHODOLOGY AND PRINCIPAL FINDINGS: We report on the
      development of an analytical framework to quantify the relative values of various
      longitudinal infection surveillance data collected in field sites undergoing mass
      drug administrations (MDAs) for calibrating three lymphatic filariasis (LF)
      models (EPIFIL, LYMFASIM, and TRANSFIL), and for improving their predictions of
      the required durations of drug interventions to achieve parasite elimination in
      endemic populations. The relative information contribution of site-specific data
      collected at the time points proposed by the WHO monitoring framework was
      evaluated using model-data updating procedures, and via calculations of the
      Shannon information index and weighted variances from the probability
      distributions of the estimated timelines to parasite extinction made by each
      model. Results show that data-informed models provided more precise forecasts of
      elimination timelines in each site compared to model-only simulations. Data
      streams that included year 5 post-MDA microfilariae (mf) survey data, however,
      reduced each model's uncertainty most compared to data streams containing only
      baseline and/or post-MDA 3 or longer-term mf survey data irrespective of MDA
      coverage, suggesting that data up to this monitoring point may be optimal for
      informing the present LF models. We show that the improvements observed in the
      predictive performance of the best data-informed models may be a function of
      temporal changes in inter-parameter interactions. Such best data-informed models
      may also produce more accurate predictions of the durations of drug interventions
      required to achieve parasite elimination. SIGNIFICANCE: Knowledge of relative
      information contributions of model only versus data-informed models is valuable
      for improving the usefulness of LF model predictions in management decision
      making, learning system dynamics, and for supporting the design of parasite
      monitoring programmes. The present results further pinpoint the crucial need for
      longitudinal infection surveillance data for enhancing the precision and accuracy
      of model predictions of the intervention durations required to achieve parasite
      elimination in an endemic location.

PMID- 30296267
TI  - LytTR Regulatory Systems: A potential new class of prokaryotic sensory system.
AB  - The most commonly studied prokaryotic sensory signal transduction systems include
      the one-component systems, phosphosignaling systems, extracytoplasmic function
      (ECF) sigma factor systems, and the various types of second messenger systems.
      Recently, we described the regulatory role of two separate sensory systems in
      Streptococcus mutans that jointly control bacteriocin gene expression, natural
      competence development, as well as a cell death pathway, yet they do not function
      via any of the currently recognized signal transduction paradigms. These systems,
      which we refer to as LytTR Regulatory Systems (LRS), minimally consist of two
      proteins, a transcription regulator from the LytTR Family and a transmembrane
      protein inhibitor of this transcription regulator. Here, we provide evidence
      suggesting that LRS are a unique uncharacterized class of prokaryotic sensory
      system. LRS exist in a basal inactive state. However, when LRS membrane inhibitor
      proteins are inactivated, an autoregulatory positive feedback loop is triggered
      due to LRS regulator protein interactions with direct repeat sequences located
      just upstream of the -35 sequences of LRS operon promoters. Uncharacterized LRS
      operons are widely encoded by a vast array of Gram positive and Gram negative
      bacteria as well as some archaea. These operons also contain unique direct repeat
      sequences immediately upstream of their operon promoters indicating that positive
      feedback autoregulation is a globally conserved feature of LRS. Despite the
      surprisingly widespread occurrence of LRS operons, the only characterized
      examples are those of S. mutans. Therefore, the current study provides a useful
      roadmap to investigate LRS function in the numerous other LRS-encoding organisms.

PMID- 30296268
TI  - Ligand binding properties of two Brugia malayi fatty acid and retinol (FAR)
      binding proteins and their vaccine efficacies against challenge infection in
      gerbils.
AB  - Parasitic nematodes produce an unusual class of fatty acid and retinol (FAR)
      binding proteins that may scavenge host fatty acids and retinoids. Two FARs from
      Brugia malayi (Bm-FAR-1 and Bm-FAR-2) were expressed as recombinant proteins, and
      their ligand binding, structural characteristics, and immunogenicities examined.
      Circular dichroism showed that rBm-FAR-1 and rBm-FAR-2 are similarly rich in
      alpha-helix structure. Unexpectedly, however, their lipid binding activities were
      found to be readily differentiated. Both FARs bound retinol and cis-parinaric
      acid similarly, but, while rBm-FAR-1 induced a dramatic increase in fluorescence
      emission and blue shift in peak emission by the fluorophore-tagged fatty acid
      (dansyl-undecanoic acid), rBm-FAR-2 did not. Recombinant forms of the related
      proteins from Onchocerca volvulus, rOv-FAR-1 and rOv-FAR-2, were found to be
      similarly distinguishable. This is the first FAR-2 protein from parasitic
      nematodes that is being characterized. The relative protein abundance of Bm-FAR-1
      was higher than Bm-FAR-2 in the lysates of different developmental stages of B.
      malayi. Both FAR proteins were targets of strong IgG1, IgG3 and IgE antibody in
      infected individuals and individuals who were classified as endemic normal or
      putatively immune. In a B. malayi infection model in gerbils, immunization with
      rBm-FAR-1 and rBm-FAR-2 formulated in a water-in-oil-emulsion ((r)Montanide-720)
      or alum elicited high titers of antigen-specific IgG, but only gerbils immunized
      with rBm-FAR-1 formulated with the former produced a statistically significant
      reduction in adult worms (68%) following challenge with B. malayi infective
      larvae. These results suggest that FAR proteins may play important roles in the
      survival of filarial nematodes in the host, and represent potential candidates
      for vaccine development against lymphatic filariasis and related filarial
      infections.

PMID- 30296270
TI  - Predicting position along a looping immune response trajectory.
AB  - When we get sick, we want to be resilient and recover our original health. To
      measure resilience, we need to quantify a host's position along its disease
      trajectory. Here we present Looper, a computational method to analyze
      longitudinally gathered datasets and identify gene pairs that form looping
      trajectories when plotted in the space described by these phases. These loops
      enable us to track where patients lie on a typical trajectory back to health. We
      analyzed two publicly available, longitudinal human microarray datasets that
      describe self-resolving immune responses. Looper identified looping gene pairs
      expressed by human donor monocytes stimulated by immune elicitors, and in YF17D
      vaccinated individuals. Using loops derived from training data, we found that we
      could predict the time of perturbation in withheld test samples with accuracies
      of 94% in the human monocyte data, and 65-83% within the same cohort and in two
      independent cohorts of YF17D vaccinated individuals. We suggest that Looper will
      be useful in building maps of resilient immune processes across organisms.

PMID- 30296269
TI  - Reactive oxygen species mediate conical cell shaping in Arabidopsis thaliana
      petals.
AB  - Plants have evolved diverse cell types with distinct sizes, shapes, and
      functions. For example, most flowering plants contain specialized petal conical
      epidermal cells that are thought to attract pollinators and influence light
      capture and reflectance, but the molecular mechanisms controlling conical cell
      shaping remain unclear. Here, through a genetic screen in Arabidopsis thaliana,
      we demonstrated that loss-of-function mutations in ANGUSTIFOLIA (AN), which
      encodes for a homolog of mammalian CtBP/BARs, displayed conical cells phenotype
      with wider tip angles, correlating with increased accumulation of reactive oxygen
      species (ROS). We further showed that exogenously supplied ROS generated similar
      conical cell phenotypes as the an mutants. Moreover, reduced endogenous ROS
      levels resulted in deceased tip sharpening of conical cells. Furthermore, through
      enhancer screening, we demonstrated that mutations in katanin (KTN1) enhanced
      conical cell phenotypes of the an-t1 mutants. Genetic analyses showed that AN
      acted in parallel with KTN1 to control conical cell shaping. Both increased or
      decreased ROS levels and mutations in AN suppressed microtubule organization into
      well-ordered circumferential arrays. We demonstrated that the AN-ROS pathway
      jointly functioned with KTN1 to modulate microtubule ordering, correlating with
      the tip sharpening of conical cells. Collectively, our findings revealed a
      mechanistic insight into ROS homeostasis regulation of microtubule organization
      and conical cell shaping.

PMID- 30296271
TI  - Vitamin D and macrophage polarization in epicardial adipose tissue of
      atherosclerotic swine.
AB  - Vitamin D functions as a potent immunomodulator by interacting with many immune
      cells however, its role in regulating inflammation in the epicardial adipose
      tissue (EAT) is unclear. In the EAT of atherosclerotic microswine that were fed
      with deficient, sufficient or supplemented levels of vitamin D, we evaluated the
      phenotype of the macrophages. Vitamin D treatment was continued for 12 months and
      serum 25(OH)D levels were measured regularly. Infiltration of M1/M2 macrophage
      was investigated by immunostaining for CCR7 and CD206, respectively in
      conjunction with a pan macrophage marker CD14. Significant difference in the
      number of CCR7+ cells was observed in the EAT from vitamin D-deficient swine
      compared to vitamin D-sufficient or -supplemented swine. Expression of CD206
      correlated with high levels of serum 25(OH)D indicating a significant increase in
      M2 macrophages in the EAT of vitamin D-supplemented compared to -deficient swine.
      These findings suggest that vitamin D-deficiency exacerbates inflammation by
      increasing pro-inflammatory M1 macrophages, while vitamin D-supplementation
      attenuates the inflammatory cytokines and promotes M2 macrophages in EAT. This
      study demonstrates the significance of vitamin D mediated inhibition of
      macrophage mediated inflammation in the EAT during coronary intervention in
      addition to its immunomodulatory role. However, additional studies are required
      to identify the cellular mechanisms that transduce signals between macrophages
      and smooth muscle cells during restenosis in the presence and absence of vitamin
      D.

PMID- 30296272
TI  - Reference genes selection for quantitative gene expression studies in tea green
      leafhoppers, Empoasca onukii Matsuda.
AB  - Empoasca onukii Matsuda is one of the most devastating pests of the tea plant
      (Camellia sinensis). Still, the presumed expression stability of its reference
      genes (RGs) has not been analyzed. RGs are essential for accurate and reliable
      gene expression analysis, so this absence has hampered the study of the insect's
      molecular biology. To find candidate RGs for normalizing gene expression data, we
      cloned ten common housekeeping genes from E. onukii. Using the DeltaCt method,
      geNorm, NormFinder and BestKeeper, we screened the RGs that were appropriate for
      quantifying the mRNA transcription of cellular responses under five experimental
      conditions. We identified the combinations of alpha-TUB and G6PDH, alpha-TUB and
      UBC, two RGs (alpha-TUB and beta-TUB1) or three RGs (alpha-TUB, RPL13 and GAPDH),
      AK and UBC, or RPL13 and alpha-TUB as the best for analyzing gene expression in
      E. onukii adults of both sexes in different tissues, nymphs at different
      developmental stages, nymphs exposed to different temperatures or nymphs exposed
      to photoperiod stress. Finally, the E. onukii cysteine proteinase (Eocyp) was
      chosen as the target gene to validate the rationality of the proposed RGs. In
      conclusion, our study suggests a series of RGs with which to study the gene
      expression profiles of E. onukii that have been manipulated (biotically or
      abiotically) using reverse transcription quantitative polymerase chain reaction.
      The results offer a solid foundation for further studies of the molecular biology
      of E. onukii.

PMID- 30296274
TI  - Stabilization period before capturing an ultra-short vagal index can be shortened
      to 60 s in endurance athletes and to 90 s in university students.
AB  - PURPOSE: To find the shortest, acceptable stabilization period before recording
      resting, supine ultra-short-term Ln RMSSD and heart rate (HR). METHOD: Thirty
      endurance-trained male athletes (age 24.1 +/- 2.3 years, maximal oxygen
      consumption (VO2max) 64.1 +/- 6.6 ml.kg-1.min-1) and 30 male students (age 23.3
      +/- 1.8 years, VO2max 52.8 +/- 5.1 ml.kg-1.min-1) were recruited. Upon awaking at
      home, resting, supine RR intervals were measured continuously for 10 min using a
      Polar V800 HR monitor. Ultra-short-term Ln RMSSD and HR values were calculated
      from 1-min RR interval segments after stabilization periods from 0 to 4 min in
      0.5 min increments and were compared with reference values calculated from 5-min
      segment after 5-min stabilization. Systematic bias and intraclass correlation
      coefficients (ICC) including 90% confidence intervals (CI) were calculated and
      magnitude based inference was conducted. RESULTS: The stabilization periods of up
      to 30 s for athletes and up to 60 s for students showed positive (possibly to
      most likely) biases for ultra-short-term Ln RMSSD compared with reference values.
      Stabilization periods of 60 s for athletes and 90 s for students showed trivial
      biases and ICCs were 0.84; 90% CI 0.72 to 0.91, and 0.88; 0.79 to 0.94,
      respectively. For HR, biases were trivial and ICCs were 0.93; 0.88 to 0.96, and
      0.93; 0.88 to 0.96, respectively. CONCLUSION: The shortest stabilization period
      required to stabilize Ln RMSSD and HR was set at 60 s for endurance-trained
      athletes and 90 s for university students.

PMID- 30296273
TI  - Monitoring the age-specificity of measles transmissions during 2009-2016 in
      Southern China.
AB  - BACKGROUND: Despite several immunization efforts, China saw a resurgence of
      measles in 2012. Monitoring of transmissions of individuals from different age
      groups could offer information that would be valuable for planning adequate
      disease control strategies. We compared the age-specific effective reproductive
      numbers (R) of measles during 2009-2016 in Guangdong, China. METHODS: We
      estimated the age-specific R values for 7 age groups: 0-8 months, 9-18 months, 19
      months to 6 years, 7-15 years, 16-25 years, 26-45 years, and >=46 years adapting
      the contact matrix of China. The daily numbers of laboratory and clinically
      confirmed cases reported to the Center for Disease Control and Prevention of
      Guangdong were used. RESULTS: The peak R values of the entire population were
      above unity from 2012 to 2016, indicating the persistence of measles in the
      population. In general, children aged 0-6 years and adults aged 26-45 years had
      larger values of R when comparing with other age groups after 2012. While the
      peaks of R values for children aged 0-6 years dropped steadily after 2013, the
      peaks of R values for adults aged 26-45 years kept at a high range every year.
      CONCLUSIONS: Although the provincial supplementary immunization activities (SIAs)
      conducted in 2009 and 2010 were able to reduce the transmissions from 2009 to
      2011, larger values of R for children aged 0-6 years were observed after 2012,
      indicating that the benefits of the SIAs were short-lived. In addition, the
      transmissions from adults aged between 26 and 45 years increased over time.
      Disease control strategies should target children and adult groups that carry
      high potential for measles transmission.

PMID- 30296275
TI  - Unraveling fine-scale habitat use for secretive species: When and where toads are
      found when not breeding.
AB  - A good understanding of species-habitat associations, or habitat use, is required
      to establish conservation strategies for any species. Many amphibian species are
      elusive and most information concerning amphibian habitat use comes from breeding
      sites where they are comparatively easy to find and study. Knowledge about
      retreat sites is extremely limited for most species and for the greater part of
      the year. For such species, it is especially important to factor in detection
      probability in habitat analyses, because otherwise distorted views about habitat
      preferences may result, e.g., when a species is more visible in habitat type B
      than in A, even though A may be preferred. The South American red-belly toad,
      Melanophryniscus pachyrhynus, is a range-restricted species from Southern Brazil
      and Uruguay that inhabits open areas with rocky outcrops and is usually seen only
      during explosive breeding events. Here we studied the fine-scale habitat use of
      the red-belly toad outside of the breeding season to identify retreat sites and
      test for the importance of accounting for species imperfect detection, using
      Bayesian occupancy models. We identified shrub density and the number of loose
      rocks as important predictors of occupancy, while detection probability was
      highest at intermediate temperatures. Considering the harsh (dry and hot)
      conditions of rocky outcrops, shrubs and loose rocks may both work as important
      refuges, besides providing food resources and protecting against predation. Rocky
      outcrops have been suffering changes in habitat configuration and we identify
      nonbreeding habitat preferences at a fine scale, which may help to promote
      population persistence, and highlight the importance of accounting for imperfect
      detection when studying secretive species.

PMID- 30296277
TI  - Elevated cytokine levels in vitreous as biomarkers of disease severity in
      infectious endophthalmitis.
AB  - PURPOSE: To investigate the immunopathogenesis of endophthalmitis, and determine
      if cytokine profiles could serve as biomarkers of disease severity in infectious
      endophthalmitis. MATERIALS AND METHODS: Vitreous samples of 46 patients
      clinically diagnosed as endophthalmitis (of which 25 were culture positive) and
      20 non-infectious controls from patients with Retinal Detachment (RD) or diabetic
      retinopathy were included in the study. The cytokine and chemokine expression
      patterns of 40 immune mediators including 6 antiinflammatory cytokines, 15
      proinflammatory cytokines, 9 Growth factors and 10 proinflammatory chemokines in
      the vitreous were were analyzed by multiplex cytokine immunoassay. In addition,
      significant immune mediators were correlated with initial and final visual acuity
      (VA). RESULTS: Our results demonstrated elevated expression of 16 mediators such
      as GCSF, GRO, IFN-gamma, IL-1alpha, IL-1beta, IL-1 RA, IL-6, IL-8, IP-10, MCP-1,
      MCP-3, MIP-1alpha, IL-1beta, TGF-alpha, TNF-alpha in patients with culture
      positive endophthalmitis. Cytokine profile expression significantly differed
      between patients with proven endophthalmitis and the non-infectious controls in
      heat map analysis. PCoA plot indicated five mediators (IL-1RA, IL-6, IL-8, GRO, G
      CSF) as biomarkers that could be Independent Predictors of Disease especially in
      culture negative cases. Correlation of cytokines with VA revealed strong
      association between the initial VA and intraocular levels of TGF-alpha, IL-1beta
      and IL-8 but there was no correlation with the severity or visual outcome of
      infection. CONCLUSION: In comparison to non-infectious ocular conditions, the
      pathogenesis of infectious endophthalmitis correlates with increased expression
      levels of IL-1RA, IL-6, IL-8, GRO, G-CSF. Understanding cytokine profiles in
      culture negative endophthalmitis patients could aid in therapy in non-responders
      to empirical antibiotic therapy.

PMID- 30296278
TI  - The evolution of cooperation in signed networks under the impact of structural
      balance.
AB  - Structural balance plays an important role in the dynamics of signed networks.
      Based on structural balance, we generalize the evolution of cooperation in signed
      networks. Here we develop a new simulation model to study the impact of
      structural balance on the evolution of cooperation in signed networks. The
      simulation shows that cooperation prevails when an individual has a higher
      probability of adjusting the signs of its relations. We also find that structural
      balance forces the coexistence of cooperators and defectors, while the initial
      attributes of networks have little impact on the evolution of cooperation in the
      presence of structural balance, although they have a strong effect on the
      evolution of structural balance.

PMID- 30296276
TI  - Adolescent binge ethanol-induced loss of basal forebrain cholinergic neurons and
      neuroimmune activation are prevented by exercise and indomethacin.
AB  - Basal forebrain cholinergic neurons mature in adolescence coinciding with
      development of adult cognitive function. Preclinical studies using the rodent
      model of adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-days on/2-days
      off from postnatal day [P]25 to P55) reveal persistent increases of brain
      neuroimmune genes that are associated with cognitive dysfunction. Adolescent
      intermittent ethanol exposure also reduces basal forebrain expression of choline
      acetyltransferase (ChAT), an enzyme critical for acetylcholine synthesis in
      cholinergic neurons similar to findings in the post-mortem human alcoholic basal
      forebrain. We report here that AIE decreases basal forebrain ChAT+IR neurons in
      both adult female and male Wistar rats following early or late adolescent ethanol
      exposure. In addition, we find reductions in ChAT+IR somal size as well as the
      expression of the high-affinity nerve growth factor (NGF) receptor tropomyosin
      receptor kinase A (TrkA) and the low-affinity NGF receptor p75NTR, both of which
      are expressed on cholinergic neurons. The decrease in cholinergic neuron marker
      expression was accompanied by increased phosphorylation of NF-kappaB p65 (pNF
      kappaB p65) consistent with increased neuroimmune signaling. Voluntary wheel
      running from P24 to P80 prevented AIE-induced cholinergic neuron shrinkage and
      loss of cholinergic neuron markers (i.e., ChAT, TrkA, and p75NTR) as well as the
      increase of pNF-kappaB p65 in the adult basal forebrain. Administration of the
      anti-inflammatory drug indomethacin (4.0 mg/kg, i.p prior to each ethanol
      exposure) during AIE also prevented the loss of basal forebrain cholinergic
      markers and the concomitant increase of pNF-kappaB p65. In contrast, treatment
      with the proinflammatory immune activator lipopolysaccharide (1.0 mg/kg, i.p. on
      P70) caused a loss of cholinergic neuron markers that was paralleled by increased
      pNF-kappaB p65 in the basal forebrain. These novel findings are consistent with
      AIE causing lasting activation of the neuroimmune system that contributes to the
      persistent loss of basal forebrain cholinergic neurons in adulthood.

PMID- 30296279
TI  - Differentiation and quantification of fibrosis, fat and fatty fibrosis in human
      left atrial myocardium using ex vivo MRI.
AB  - BACKGROUND: Atrial fibrillation is associated with an atrial cardiomyopathy
      composed mainly of fibrosis and adipose tissue accumulation. We hypothesized that
      MRI, when used in an optimal ex vivo setting allowing high spatial resolution
      without motion artifacts, can help characterizing the complex 3D left atrial (LA)
      wall composition in human myocardial samples, as compared to histology. METHODS:
      This prospective case-control study was approved by the institutional review
      board. 3D MRI acquisitions including saturation-recovery T1 mapping and DIXON
      imaging was performed at 4.0 T on 9 human LA samples collected from patients who
      underwent cardiac surgery. Histological quantification of fibrosis and fat was
      obtained. MRI T1 maps were clustered based on a Gaussian Mixture Model allowing
      quantification of total, interstitial and fatty fibrosis components. Fat maps
      were computed from DIXON images and fat fractions were calculated. MRI
      measurements were performed on the same location as the histological analysis
      (plane) and on the entire sample volume (3D). RESULTS: High correlations and
      levels of agreement were observed between MRI and histology for total (r = 0.93),
      interstitial (r = 0.93) and fatty fibrosis (r = 0.98) and fat (r = 0.96). Native
      T1 correlated with the amount of fibrosis from MRI and histology. The 3D MRI
      total, interstitial and fatty fibrosis ranges were between 6% and 23%, 4% and
      17.3%; and 1.4% and 19.7% respectively. CONCLUSION: High Field ex vivo MRI was
      able to quantify different LA myocardial components with high agreement in 2D
      with histology and moreover to provide 3D quantification of such components
      whereas in vivo application remains a challenge.

PMID- 30296280
TI  - Galactography is not an obsolete investigation in the evaluation of pathological
      nipple discharge.
AB  - PURPOSE: To evaluate the malignancy rate and diagnostic performance of
      galactography in patients with pathological nipple discharge (PND) after negative
      clinical breast examination, mammography and ultrasound. MATERIALS AND METHODS:
      We retrospectively evaluated all galactograms obtained between January 2006 and
      December 2014 in women with PND. Galactographic findings were classified into 6
      groups according to a modified Galactogram Image Classification system (GICS) to
      comply with the breast imaging reporting and data system classification.
      Observers were blinded to the final histology and clinical outcome at the time of
      analysis. MRI was performed as a problem solving ancillary examination. Imaging
      findings, pathological diagnosis and follow-up data were evaluated. The
      diagnostic performance of MRI and technically successful galactography in the
      detection of neoplastic or risk lesions were separately calculated. RESULTS: A
      total of 146 patients with PND (mean age, 51.5 years; range, 17-93) were
      examined. Malignant lesions were detected in only 4 patients (2.7%) and risk
      lesions in 5 patients (3.4%). Only one low-grade ductal carcinoma in situ was
      missed by galactography (GICS 1) and MRI. MRI examinations were performed in 21
      (14.4%) patients; one of these patients (4.8%) had a malignant finding (GICS 0),
      two (9.5%) had risk-lesions (GICS 2 and 5). In the detection of neoplastic or
      risk lesions the sensitivity and specificity of galactography were 77.4% and
      75.7% and of MRI 85.7% and 71.4%, consecutively. CONCLUSION: The malignancy rate
      is negligible if clinical, mammography, ultrasound and galactography examinations
      are negative. Galactography remains a practical, valuable and cost-effective
      examination procedure. If galactography is technically unsuccessful, MRI should
      be considered as an additional ancillary tool to evaluate the possible etiology
      of symptoms, but the routine use of MRI in all patients cannot be justified.

PMID- 30296281
TI  - Deceptive nest defence in ground-nesting birds and the risk of intermediate
      strategies.
AB  - Nest predation is an important determinant of reproductive success and ground
      nesting birds exhibit a variety of nest defence strategies to mitigate the risk.
      Many small-bodied, ground nesting birds rely on deceptive behaviours such as
      injury-feigning to reduce nest predation: we call this behaviour active
      deception. However, active deception may entail risks to adults, and passive
      deceptive behaviour, where individuals effectively sneak away from the nest by
      flushing at long distances, may be an alternative means of avoiding nest
      predation. We provide a simple model to demonstrate that these tails of the flush
      distance distribution could minimize predation risk; an intermediate strategy of
      moderate flush distances means that birds flush more often than with short
      distance flushes, and once flushed, the nest is more easily located than for long
      distance flushes. We tested this model using two species of ground nesting
      shorebirds, the White-rumped Sandpiper (Calidris fuscicollis) and the Red
      Phalarope (Phalaropus fulicarius). We demonstrate that short-distance flushes are
      associated with active deception and intermediate-distance flushes are associated
      with an increased risk of nest predation. However, we found no evidence that this
      potential selective pressure against intermediate strategies has produced a
      bimodal distribution of nest defence traits. The heritability of defence
      behaviours, or the ability of individuals to learn, is unknown and other factors
      such as energetic constraints or risks to adults might also influence flush
      distances and defence behaviours.

PMID- 30296282
TI  - Root growth, function and rhizosphere microbiome analyses show local rather than
      systemic effects in apple plant response to replant disease soil.
AB  - Apple replant disease (ARD) is the phenomenon of soil decline occurring after
      repeated planting of apple trees at the same site. This study aimed to elucidate
      whether ARD is systemic, i.e. whether the contact of parts of the root system
      with ARD soil causes the whole plant to show poor shoot and root growth. A split
      root experiment was conducted with seedlings of 'M26', offering the same plant
      for its root system the choice between the substrates ARD soil (+ARD), gamma
      sterilized ARD soil (-ARD) or soil from a grass parcel (Control) with the
      following combinations: +ARD/+ARD, -ARD/-ARD; +ARD/-ARD; +ARD/Control. Root
      growth was analysed throughout the 34-day growing period. Samples from bulk,
      rhizosphere and rhizoplane soil were collected separately for each compartment,
      and analysed by fingerprints of 16S rRNA gene or ITS fragments amplified from
      total community (TC) DNA. The response of the plant to +ARD was not systemic as
      root growth in -ARD compartment was always superior to root growth in +ARD soil.
      Crosswise 15N-labelling of the N-fertilizer applied to the split-root
      compartments showed that nitrate-N uptake efficiency was higher for roots in -ARD
      soil compared to those in +ARD. Bacterial and fungal community composition in the
      rhizoplane and rhizosphere of the same plants differed significantly between the
      compartments containing +ARD/-ARD or +ARD/Control. The strongest differences
      between the bacterial fingerprints were observed in the rhizoplane and
      rhizosphere. Bacterial genera with increased abundance in response to ARD were
      mainly Streptomyces but also Sphingobium, Novosphingobium, Rhizobium, Lysobacter
      and Variovorax. The strongest differences between the fungal fingerprints were
      observed in bulk soil. Our data showed that the response of the apple plant to
      ARD soil is local and not systemic.

PMID- 30296283
TI  - Impact of social capital, harassment of women and girls, and water and sanitation
      access on premature birth and low infant birth weight in India.
AB  - BACKGROUND: Globally, preterm birth (PTB) and low infant birth weight (LBW) are
      leading causes of maternal and child morbidity and mortality. Inadequate water
      and sanitation access (WASH) are risk factors for PTB and LBW in low-income
      countries. Physical stress from carrying water and psychosocial stress from
      addressing sanitation needs in the open may be mechanisms underlying these
      associations. If so, then living in a community with strong social capital should
      be able to buffer the adverse effects of WASH on birth outcomes. The objective of
      this study is to assess the relationships between WASH access and social
      conditions (including harassment and social capital) on PTB and LBW outcomes
      among Indian women, and to test whether social conditions modified the
      association between WASH and birth outcomes. METHODS AND FINDINGS: This cohort
      study examined the effect of pre-birth WASH and social conditions on self
      reported PTB status and LBW status for 7,926 women who gave birth between
      2004/2005 and 2011/2012 Waves of the India Human Development Survey. PTB and LBW
      occurred in 14.9% and 15.5% of women, respectively. After adjusting for maternal
      biological and socioeconomic conditions, PTB was associated with sharing a
      building/compound latrine (Odds Ratio (OR) = 1.55; 95% Confidence Interval (CI) =
      1.01, 2.38) versus private latrine access, but suggested an effect in the
      opposite direction for sharing a community/public latrine (OR = 0.67; CI = 0.45,
      1.01). Open defecation, type of drinking water source, minutes per day spent
      fetching water, and one-way time to a drinking water source were not associated
      with PTB. LBW was associated with spending more than two hours per day fetching
      water compared to less than two hours (OR = 1.33; CI = 1.05, 1.70) and suggested
      an association with open defecation (OR = 1.22; CI = 1.00, 1.48), but was not
      associated with other types of sanitation, type of drinking water source, or time
      to a drinking water source. Harassment of women and girls in the community was
      associated with both PTB (OR = 1.33; CI = 1.09, 1.62) and LBW (OR = 1.26; CI =
      1.03, 1.54). The data also showed a possible association of local crime with LBW
      (OR = 1.30; CI = 1.00, 1.68). Statistically significant (p<0.05) evidence of
      effect modification was only found for collective efficacy on the association
      between type of sanitation access and PTB. In addition, stratified analyses
      identified differences in effect size for walking time to the primary drinking
      water source and PTB by crime, sanitation access and PTB by harassment, and total
      hours per day fetching water and LBW by collective efficacy. Limitations of this
      observational study include risk of bias, inability to confirm causality,
      reliance on self-reported outcomes, and limited sub-group sample sizes for
      testing effect modification. CONCLUSIONS: The relationship between adverse birth
      outcomes and sanitation access, domestic water fetching, crime, and gender-based
      harassment suggests physical and psychosocial stress are possible mechanisms by
      which WASH access affects PTB and LBW among Indian women. Interventions that
      reduce domestic responsibilities related to water and sanitation and change
      social norms related to gender-based harassment may reduce rates of PTB and LBW
      in India.

PMID- 30296284
TI  - Establishment of five immortalized human ovarian surface epithelial cell lines
      via SV40 T antigen or HPV E6/E7 expression.
AB  - BACKGROUND: Human ovarian surface epithelial (HOSE) cells are a critical cell
      source for ovarian cancer research; however, they are difficult to obtain and
      maintain under standard laboratory conditions in large quantities. The aim of
      this study was to generate immortalized HOSE (IHOSE) cells with maintained
      properties to the original cell source, thereby guaranteeing a sufficiently large
      cell quantity for ovarian cancer research. METHODS: HOSE cells isolated from four
      non-cancer patients and five IHOSE cell lines were established by induction of
      HPV-E6/E7 expression or SV40 large T antigen using a lenti-viral system. Each of
      IHOSE cells was confirmed to be distinct by STR profiling. RNA-sequencing was
      used to compare gene expression profiles in HOSE, IHOSE and ovarian cancer cells.
      RESULTS: RNA-sequencing results revealed a stronger linear correlation in gene
      expression between IHOSE and HOSE cells (R2 = 0.9288) than between IHOSE or HOSE
      cells and ovarian cancer cells (R2 = 0.8562 and R2 = 0.7982, respectively). The
      gene expression pattern of 319 differentially expressed genes revealed minimal
      differences between HOSE and IHOSE cells, while a strong difference between
      ovarian cancer cells and HOSE or IHOSE cells was observed. Furthermore, the five
      IHOSE cell lines displayed morphological characteristics typical of epithelial
      cells but showed a lower level of EpCAM, CD133 and E-cadherin, as cancer stem
      marker, than ovarian cancer cells. Moreover, unlike cancer cells, IHOSE cells
      could not form colonies in the anchorage-independent soft agar growth assay.
      CONCLUSION: These findings demonstrate that five newly established IHOSE cell
      lines have characteristics of progenitor HOSE cells while exhibiting continuous
      growth, and thus, should be highly useful as control cells for ovarian cancer
      research.

PMID- 30296285
TI  - Seagrass and macrophyte mediated CO2 and CH4 dynamics in shallow coastal waters.
AB  - Seagrass meadows are among the most important coastal/ marine ecosystems for long
      term carbon storage and conditioning of coastal waters. A combined air-water flux
      of CO2 and CH4 from the seagrass meadows was studied for the first time from
      Asia's largest brackish-water lagoon, Chilika, India. Ecosystem-based comparisons
      were carried out during two hydrologically different conditions of dry and wet
      seasons in the seagrass dominated southern sector (SS); macrophyte-dominated
      northern sector (NS); the largely un-vegetated central sector (CS) and the
      tidally active outer channel (OC) of the lagoon. The mean fluxes of CO2 from SS,
      NS, CS and OC were 9.8, 146.6, 48.4 and 33.0mM m-2d-1, and that of CH4 were 0.12,
      0.11, 0.05 and 0.07mM m-2d-1, respectively. The net emissions (in terms of CO2
      equivalents), considering the global warming potential of CO2 (GWP: 1) and CH4
      (GWP: 28) from seagrass meadows were over 14 times lower compared to the
      macrophyte-dominated sector of the lagoon. Contrasting emissivity characteristics
      of CO2 and CH4 were observed between macrophytes and seagrass, with the former
      being a persistent source of CO2. It is inferred that although seagrass meadows
      act as a weak source of CH4, they could be effective sinks of CO2 if land-based
      pollution sources are minimized.

PMID- 30296286
TI  - Sports participation in sport clubs, gyms or public spaces: How users of
      different sports settings differ in their motivations, goals, and sports
      frequency.
AB  - BACKGROUND: To develop targeted policy strategies to increase sports
      participation, more insight is needed into the behavioural patterns and
      preferences of users of different club-organized (i.e., sports clubs) and non
      club organized (i.e., gyms, health centres or swimming pools) or informal sports
      settings such as public spaces. This study investigates 1) how users of different
      settings differ regarding self-determined motivations and goals, and
      sociodemographic and sports-related characteristics, and 2) how the association
      of motivations and goals with sports participation may differ between users of
      different sports settings. METHODS: Data were collected through online surveys
      among Dutch adults aged 18-80 years (N = 910). Ordinal regression analyses were
      used to investigate the effects of sports settings, the level of self-determined
      motivations and goals, and interaction effects of motivations and goals with
      different sports settings, on sports frequency. RESULTS: Users of different
      sports settings differed in their personal characteristics, motivations and
      goals. In general, controlled motivations were negatively associated with sports
      frequency (B = -0.46). However, among club members, extrinsic goals related to
      image (B = 0.44), as well as intrinsic goals related to skill development (B =
      0.40) and social affiliation (B = 0.47) had significant positive associations
      with sports frequency. Health-related goals significantly increased sports
      frequency among users of informal settings, such as public spaces. CONCLUSION:
      The association of motivational variables with sports participation differs
      between settings. This implies that sports frequency is higher when participants
      engage in settings that better fit their motivations and goals. Because of the
      growing importance of informal and flexible settings and health goals,
      professionals in the sports and health domains should take into account the
      motivations, goals and needs of different target groups who (want to) use
      unorganized, informal sports settings including public spaces.

PMID- 30296287
TI  - Field evaluation of the BG-Malaria trap for monitoring malaria vectors in rural
      Tanzanian villages.
AB  - BG-Malaria (BGM) trap is a simple adaptation of the widely-used BG-Sentinel trap
      (BGS). It is proven to be highly effective for trapping the Brazilian malaria
      vector, Anopheles darlingi, in field conditions, and the African vector,
      Anopheles arabiensis, under controlled semi-field environments, but has not been
      field-tested in Africa. Here, we validated the BGM for field sampling of malaria
      vectors in south-eastern Tanzania. Using a series of Latin-Square experiments
      conducted nightly (6pm-7am) in rural villages, we compared mosquito catches
      between BGM, BGS and human landing catches (HLC). We also compared BGMs baited
      with different attractants (Ifakara-blend, Mbita-blend, BG-Lure and CO2). Lastly,
      we tested BGMs baited with Ifakara-blend from three odour-dispensing methods (BG
      Cartridge, BG-Sachet and Nylon strips). One-tenth of the field-collected female
      Anopheles gambiae s.l. and Anopheles funestus were dissected to assess parity.
      BGM captured more An. gambiae s.l. than BGS (p < 0.001), but HLC caught more than
      either trap (p < 0.001). However, BGM captured more An. funestus than HLC.
      Proportions of parous An. gambiae s.l. and An. funestus consistently exceeded
      50%, with no significant difference between methods. While the dominant species
      caught by HLC was An. gambiae s.l. (56.0%), followed by Culex spp. (33.1%) and
      Mansonia spp. (6.0%), the BGM caught mostly Culex (81.6%), followed by An.
      gambiae s.l. (10.6%) and Mansonia (5.8%). The attractant-baited BGMs were all
      significantly superior to un-baited controls (p < 0.001), although no difference
      was found between the specific attractants. The BG-Sachet was the most efficient
      dispenser for capturing An. gambiae s.l. (14.5(2.75-42.50)
      mosquitoes/trap/night), followed by BG-Cartridge (7.5(1.75-26.25)). The BGM
      caught more mosquitoes than BGS in field-settings, but sampled similar species
      diversity and physiological states as BGS. The physiological states of malaria
      vectors caught in BGM and BGS were similar to those naturally attempting to bite
      humans (HLC). The BGM was most efficient when baited with Ifakara blend,
      dispensed from BG-Sachet. We conclude that though BGM traps have potential for
      field-sampling of host-seeking African malaria vectors with representative
      physiological states, both BGM and BGS predominantly caught more culicines than
      Anopheles, compared to HLC, which caught mostly An. gambiae s.l.

PMID- 30296288
TI  - Tobacco smoke exposure is an independent predictor of vitamin D deficiency in US
      children.
AB  - IMPORTANCE: The role of tobacco-smoke exposure on serum vitamin D concentration
      in US pediatric population is not known. We hypothesized that tobacco smoke
      exposure would increase the prevalence of vitamin D deficiency in US children.
      METHODS: Representative national data were accessed from the National Health and
      Nutrition Examination Survey (NHANES) 2009-2010 databank on 2,263 subjects of
      ages 3 to 17 years. Subjects were categorized into two groups based on their age:
      children, if <10 years; and youth if 10 to 17 years. Descriptive and multiple
      logistic regression analyses were conducted to determine the effect of serum
      cotinine-verified tobacco smoke exposure on vitamin D status after controlling
      for key sociodemographic confounders. Vitamin D deficiency was defined as 25(OH)D
      <20 ng/mL, insufficiency as 25(OH)D of 20-29.9 ng/mL, and sufficiency as 25(OH)D
      of >=30 ng/mL. Tobacco smoke exposure status was defined by serum cotinine
      concentration as follows: unexposed and non-smoking (<0.05 ng/mL) and exposed
      (passive and active smokers combined) (>=0.05ng/mL). Specifically, passive and
      active smoking were defined as cotinine of 0.05-10 ng/mL, and >=10ng/mL
      respectively. RESULTS: The prevalence of second-hand smoke exposure was 42.0%
      (95%CI, 36.7%-47.5%); while the prevalence of active smoking among teenagers was
      9.0% (95%CI, 6.2%-12.5%). Vitamin D deficiency occurred at a frequency of 15.1%
      in children unexposed to tobacco smoke, 20.9% in children exposed to passive
      tobacco smoke, and 18.0% among actively smoking youth (p<0.001). Tobacco smoke
      exposure independently predicted vitamin D deficiency after controlling for age,
      sex, race, BMI, maternal education, and family socio-economic status (OR:1.50;
      95%CI, 1.14-1.85, p = 0.002). CONCLUSIONS: This analysis of a nationwide database
      reports that tobacco smoke exposure is an independent predictor of vitamin D
      deficiency in US children.

PMID- 30296289
TI  - Correcting geometric distortions in stereoscopic 3D imaging.
AB  - Motion in a distorted virtual 3D space may cause visually induced motion
      sickness. Geometric distortions in stereoscopic 3D can result from mismatches
      among image capture, display, and viewing parameters. Three pairs of potential
      mismatches are considered, including 1) camera separation vs. eye separation, 2)
      camera field of view (FOV) vs. screen FOV, and 3) camera convergence distance
      (i.e., distance from the cameras to the point where the convergence axes
      intersect) vs. screen distance from the observer. The effect of the viewer's head
      positions (i.e., head lateral offset from the screen center) is also considered.
      The geometric model is expressed as a function of camera convergence distance,
      the ratios of the three parameter-pairs, and the offset of the head position. We
      analyze the impacts of these five variables separately and their interactions on
      geometric distortions. This model facilitates insights into the various
      distortions and leads to methods whereby the user can minimize geometric
      distortions caused by some parameter-pair mismatches through adjusting of other
      parameter pairs. For example, in postproduction, viewers can correct for a
      mismatch between camera separation and eye separation by adjusting their distance
      from the real screen and changing the effective camera convergence distance.

PMID- 30296290
TI  - Automated classification of synaptic vesicles in electron tomograms of C. elegans
      using machine learning.
AB  - Synaptic vesicles (SVs) are a key component of neuronal signaling and fulfil
      different roles depending on their composition. In electron micrograms of
      neurites, two types of vesicles can be distinguished by morphological criteria,
      the classical "clear core" vesicles (CCV) and the typically larger "dense core"
      vesicles (DCV), with differences in electron density due to their diverse cargos.
      Compared to CCVs, the precise function of DCVs is less defined. DCVs are known to
      store neuropeptides, which function as neuronal messengers and modulators [1]. In
      C. elegans, they play a role in locomotion, dauer formation, egg-laying, and
      mechano- and chemosensation [2]. Another type of DCVs, also referred to as
      granulated vesicles, are known to transport Bassoon, Piccolo and further
      constituents of the presynaptic density in the center of the active zone (AZ),
      and therefore are important for synaptogenesis [3]. To better understand the role
      of different types of SVs, we present here a new automated approach to classify
      vesicles. We combine machine learning with an extension of our previously
      developed vesicle segmentation workflow, the ImageJ macro 3D ART VeSElecT. With
      that we reliably distinguish CCVs and DCVs in electron tomograms of C. elegans
      NMJs using image-based features. Analysis of the underlying ground truth data
      shows an increased fraction of DCVs as well as a higher mean distance between
      DCVs and AZs in dauer larvae compared to young adult hermaphrodites. Our machine
      learning based tools are adaptable and can be applied to study properties of
      different synaptic vesicle pools in electron tomograms of diverse model
      organisms.

PMID- 30296292
TI  - Models of turfgrass seed germination related to water content.
AB  - Turfgrasses have been widely utilized by humans to enhance the environment for
      more than several centuries. Seed germination is of great importance in the
      development of the turfgrass industry. In this study, the seed germination models
      of the responses of three types of turfgrasses to water were studied. The results
      indicated that irrigation water was mainly related to the variation of seed
      volume rather than a fixed value in this experiment. The maximum k value of tall
      fescue, Kentucky bluegrass and perennial ryegrass is 1.1548, 1.6946 and 4.0940,
      respectively. The optimal value of k is 1.0617 for tall fescue, 1.4610 for
      Kentucky bluegrass, and 1.6614 for perennial ryegrass. Perennial ryegrass seeds
      are more sensitive to water than those of tall fescue and Kentucky bluegrass, and
      this turfgrass is the fastest to reach the maximum value of the germination rate.
      Based on the results from the present experiment, the seed germination function
      can describe the response of turfgrass seed germination to external water content
      variation and their sensitivities. The function obtained could be used to perform
      quantitative studies on the dynamic changes of seed germination under different
      water conditions that will contribute to improved predictions of the optimal
      fitting curves of the germination over a range of water.

PMID- 30296291
TI  - Three-dimensional holographic visualization of high-resolution myocardial scar on
      HoloLens.
AB  - Visualization of the complex 3D architecture of myocardial scar could improve
      guidance of radio-frequency ablation in the treatment of ventricular tachycardia
      (VT). In this study, we sought to develop a framework for 3D holographic
      visualization of myocardial scar, imaged using late gadolinium enhancement (LGE),
      on the augmented reality HoloLens. 3D holographic LGE model was built using the
      high-resolution 3D LGE image. Smooth endo/epicardial surface meshes were
      generated using Poisson surface reconstruction. For voxel-wise 3D scar model,
      every scarred voxel was rendered into a cube which carries the actual resolution
      of the LGE sequence. For surface scar model, scar information was projected on
      the endocardial surface mesh. Rendered layers were blended with different
      transparency and color, and visualized on HoloLens. A pilot animal study was
      performed where 3D holographic visualization of the scar was performed in 5
      swines who underwent controlled infarction and electroanatomic mapping to
      identify VT substrate. 3D holographic visualization enabled assessment of the
      complex 3D scar architecture with touchless interaction in a sterile environment.
      Endoscopic view allowed visualization of scar from the ventricular chambers. Upon
      completion of the animal study, operator and mapping specialist independently
      completed the perceived usefulness questionnaire in the six-item usefulness
      scale. Operator and mapping specialist found it useful (usefulness rating:
      operator, 5.8; mapping specialist, 5.5; 1-7 scale) to have scar information
      during the intervention. HoloLens 3D LGE provides a true 3D perception of the
      complex scar architecture with immersive experience to visualize scar in an
      interactive and interpretable 3D approach, which may facilitate MR-guided VT
      ablation.

PMID- 30296293
TI  - Immunomodulatory activity of a novel polysaccharide from Lonicera japonica in
      immunosuppressed mice induced by cyclophosphamide.
AB  - Lonicera japonica is a typical Chinese herbal medicine. We previously reported a
      method to isolate polysaccharides from Lonicera japonica (LJP). In this study, we
      first performed a qualitative analysis of LJP using the Fourier Transform
      Infrared Spectrometer (FT-IR) and explored the monosaccharide composition of LJP
      using the pre-column derivatization high performance liquid chromatography (HPLC)
      method. We then investigated the immunomodulatory function of LJP in
      cyclophosphamide (CTX)-induced immunosuppressed mouse models. The results showed
      that LJP had the characteristic absorption of typical polysaccharides consisting
      of 6 types of monosaccharides. In addition, LJP can increase significantly the
      organ index, splenic lymphocyte proliferation, macrophage phagocytosis, and
      natural killer (NK) cell activity in CTX-treated mice. LJP could also restore the
      levels of serum cytokines interleukin (IL-2), tumor necrosis factor (TNF-alpha)
      and Interferon-gamma (IFN-gamma) in the CTX-treated mice. Finally, the results on
      measuring the T-lymphocytes subsets of spleen also confirmed LJP-induced
      immunomodulatory activity in immunosuppressed mice from another perspective.
      Therefore, LJP could be used as a potential immunomodulatory agent.

PMID- 30296294
TI  - The workforce trends of physician assistants in Iowa (1995-2015).
AB  - BACKGROUND: Physician assistants are expected to have an important role in
      providing both primary and specialty care. Iowa has a large rural (and aging)
      population and faces challenges to provide equitable access to care. This study
      examined changes in the Iowa physician assistant workforce (1995-2015) focusing
      on practice setting (primary v. subspecialty care) and geographic location
      (rural/urban, Health Professional Shortage Area). Documenting their current
      locations and service in HPSAs for primary care will help health planners track
      future changes. METHODS: Data from 1995-2015 from the Iowa Health Professions
      Inventory (Office of Statewide Clinical Education Programs, Carver College of
      Medicine, University of Iowa) were combined with US census data on rural location
      and HPSA status. SPSS was used to compare Iowa and national data. Growth trends
      were analyzed using joinpoint regression. RESULTS: The overall Iowa physician
      assistant workforce increased 161% between 1995 and 2015. In 2015, more than two
      thirds (71%) were female and more than 30% practiced in rural counties. The
      average annual growth rate of primary care PAs (per 100,000 population) was
      significantly higher in the periods from 1995-1997 and 1997-2001 (22.4% and 7.4%
      respectively) than in period from 2001-2015 (3.8%). By 2015, 56% of Iowa's
      physician assistants practiced in primary care (versus 29.6% nationally). Of
      these, 44% of primary care physician assistants in Iowa practiced in counties,
      geographic locations or worksites designated as Health Professional Shortage
      Areas for primary care. CONCLUSIONS: A high proportion of Iowa's physician
      assistant workforce practiced in primary care and many served patients in Health
      Professional Shortage Areas. The number of physician assistants in Iowa will
      continue to grow and serve an important role in providing access to health care,
      particularly to rural Iowans.

PMID- 30296296
TI  - Laser surgery reveals the biomechanical and chemical signaling functions of aphid
      siphunculi (cornicles).
AB  - Aphids are an attractive food source to many predators and parasitoids because of
      their small size, soft bodies and slow movement. To combat predation, aphids
      evolved both behavioral and chemical defensive mechanisms that are operated via
      siphunculi (cornicles), differently developed structures that more or less extend
      from their abdomen. Although both direct and indirect linkages between siphunculi
      and their defensive mechanisms have been explored, their ultimate effects on
      aphid fitness are still broadly debated. To explicitly test the influence of
      siphunculi on brown citrus aphid, Aphis (Toxoptera) citricida (Kirkaldy),
      fitness, we razor-cut and laser-sealed the siphunculi. Siphunculi removal
      resulted in two distinct behavior modifications, (false aggregation and increased
      drop-off rates) that led to decreased survival and the loss of the ability to
      right themselves from an inverted position. These results together indicate that
      siphunculi play an important role in survival, and removal of these organs will
      have negative effect on aphid fitness. Furthermore, results suggested that
      released alarm pheromone may play an important role in communication among aphid
      clone-mate, and omitting it results in miscommunication and competition among
      clonemates. These findings will help in better understanding the aphid biology.

PMID- 30296295
TI  - The role of case proximity in transmission of visceral leishmaniasis in a highly
      endemic village in Bangladesh.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is characterised by a high degree of
      spatial clustering at all scales, and this feature remains even with successful
      control measures. VL is targeted for elimination as a public health problem in
      the Indian subcontinent by 2020, and incidence has been falling rapidly since
      2011. Current control is based on early diagnosis and treatment of clinical
      cases, and blanket indoor residual spraying of insecticide (IRS) in endemic
      villages to kill the sandfly vectors. Spatially targeting active case detection
      and/or IRS to higher risk areas would greatly reduce costs of control, but its
      effectiveness as a control strategy is unknown. The effectiveness depends on two
      key unknowns: how quickly transmission risk decreases with distance from a VL
      case and how much asymptomatically infected individuals contribute to
      transmission. METHODOLOGY/PRINCIPAL FINDINGS: To estimate these key parameters, a
      spatiotemporal transmission model for VL was developed and fitted to geo-located
      epidemiological data on 2494 individuals from a highly endemic village in
      Mymensingh, Bangladesh. A Bayesian inference framework that could account for the
      unknown infection times of the VL cases, and missing symptom onset and recovery
      times, was developed to perform the parameter estimation. The parameter estimates
      obtained suggest that, in a highly endemic setting, VL risk decreases relatively
      quickly with distance from a case-halving within 90m-and that VL cases contribute
      significantly more to transmission than asymptomatic individuals.
      CONCLUSIONS/SIGNIFICANCE: These results suggest that spatially-targeted
      interventions may be effective for limiting transmission. However, the extent to
      which spatial transmission patterns and the asymptomatic contribution vary with
      VL endemicity and over time is uncertain. In any event, interventions would need
      to be performed promptly and in a large radius (>=300m) around a new case to
      reduce transmission risk.

PMID- 30296297
TI  - Somatosensory and transcranial motor evoked potential monitoring in a porcine
      model for experimental procedures.
AB  - Evoked potential monitoring has evolved as an essential tool not only for
      elaborate neurological diagnostics, but also for general clinical practice.
      Moreover, it is increasingly used to guide surgical procedures and prognosticate
      neurological outcome in the critical care unit, e.g. after cardiac arrest.
      Experimental animal models aim to simulate a human-like scenario to deduct
      relevant clinical information for patient treatment and to test novel therapeutic
      opportunities. Porcine models are particularly ideal due to a comparable
      cardiovascular system and size. However, certain anatomic disparities have to be
      taken into consideration when evoked potential monitoring is used in animal
      models. We describe a non-invasive and reproducible set-up useful for different
      modalities in porcine models. We further illustrate hints to overcome multi
      faceted problems commonly occurring while using this sophisticated technique. Our
      descriptions can be used to answer a plethora of experimental questions, and help
      to further facilitate experimental therapeutic innovation.

PMID- 30296298
TI  - Assessing psychological and physical abuse from children's perspective: Factor
      structure and psychometric properties of the picture-based, modularized child
      report version of the Parent-Child Conflict Tactics Scale - Revised (CTSPC-R).
AB  - Child victims' reports of psychological and physical abuse by caregivers are a
      fundamental source of information beyond official records and caregiver reports.
      However, few or no sensitive and age-appropriate child-report instruments exist
      that have undergone in-depth validity and reliability testing across a broad age
      range. Our study addresses this gap by examining psychometric properties of a
      picture-based, modularized version of the Parent-Child Conflict Tactics Scale
      (CTSPC-R), encompassing the maltreatment subtypes of psychological and physical
      abuse. A sample of 904 children and adolescents aged 4-16 years from the
      community (n = 568), child psychiatric services (n = 159), and from Child
      Protective Services (CPS; n = 177) completed the CTSPC-R. Measures to test
      convergent (maltreatment in parent interviews and CPS records) and concurrent
      validity (psychiatric symptoms) were collected. The CTSPC-R comprises 22 items,
      arranged in three severity modules by increasing level of psychological and
      physical abuse by caregivers. Companion picture cards were provided for children
      aged 4 and 8 years. The best fit to the data was attained with a second-order
      factor model, assuming three inter-correlated factors corresponding to the three
      severity modules, and a latent second-order factor representing combined physical
      and psychological abuse. The three factors showed good internal consistencies.
      Supporting convergent validity at the global and subtype-level of maltreatment,
      the CTSPC-R severity scale was associated with lifetime CPS-contact, presence of
      caregiver-reported emotional maltreatment and physical abuse, and dimensions of
      chronicity and severity. Discriminant validity was supported by non-significant
      correlations with caregiver-reported lack of supervision, failure to provide, and
      sexual abuse. Bolstering concurrent validity, moderate and severe physical abuse
      predicted caregiver-reported internalizing and externalizing symptoms. These
      effects were independent of child age, gender or community vs. non-community
      samples. Our study supports the CTSPC-R as a scientifically and clinically sound
      tool for ascertaining the child's own perspective on psychological and physical
      abuse from an early age onwards.

PMID- 30296299
TI  - Automatic detection of cyberbullying in social media text.
AB  - While social media offer great communication opportunities, they also increase
      the vulnerability of young people to threatening situations online. Recent
      studies report that cyberbullying constitutes a growing problem among youngsters.
      Successful prevention depends on the adequate detection of potentially harmful
      messages and the information overload on the Web requires intelligent systems to
      identify potential risks automatically. The focus of this paper is on automatic
      cyberbullying detection in social media text by modelling posts written by
      bullies, victims, and bystanders of online bullying. We describe the collection
      and fine-grained annotation of a cyberbullying corpus for English and Dutch and
      perform a series of binary classification experiments to determine the
      feasibility of automatic cyberbullying detection. We make use of linear support
      vector machines exploiting a rich feature set and investigate which information
      sources contribute the most for the task. Experiments on a hold-out test set
      reveal promising results for the detection of cyberbullying-related posts. After
      optimisation of the hyperparameters, the classifier yields an F1 score of 64% and
      61% for English and Dutch respectively, and considerably outperforms baseline
      systems.

PMID- 30296300
TI  - Barriers and facilitators to adoption and use of fuel pellets and improved
      cookstoves in urban Rwanda.
AB  - BACKGROUND: The environmental and health impacts of reliance on solid fuels and
      traditional cookstoves in low-income countries have motivated the promotion of
      household cooking energy systems that use cleaner burning fuels and cookstoves
      that lead to reduced exposure to harmful pollutants. Little is known about
      adoption and use of such systems from the users' perspective. METHODS: We
      explored the facilitators and barriers to adoption and use of a private sector
      marketed household cooking energy system that uses sustainably produced biomass
      pellets and the cleanest burning fan micro-gasification stove currently
      available. We conducted 48 in-depth qualitative interviews in Gisenyi, Rwanda
      with decision-makers and cooks in 16 households that adopted the improved
      cookstove system and 8 non-adopter households. RESULTS: Reported facilitators and
      barriers to adoption and non-adoption, as well as use and non-use were complex,
      and in some cases, contradictory. Some adopters noted that cleanliness and low
      smoke production were major facilitators to adoption and use, while other
      adopters and non-adopters said the cookstoves blackened and damaged cooking pots
      and produced excessive smoke. Our findings suggest that correct use of the stove
      mediates user experience. Cost was likewise reported as a facilitator among some
      adopters and a barrier among other adopters and non-adopters. Peer influence
      played a significant role as both a barrier and a facilitator to adoption and
      transcended other factors. Positive peer influence describing the cleanliness,
      affordability, and efficiency of the cookstove system encouraged adoption and
      use, while negative comments by peers regarding excessive smoke and damaged
      cooking pots discouraged adoption. Commentaries by some participants suggest that
      inadequate training and instruction may be primary causes of the discrepancies.
      CONCLUSION: Cost, cleanliness, communication among peer networks, and adequate
      training and instruction are important factors associated with the adoption and
      use of improved cookstoves and should be prioritized in the implementation of
      improved cookstove programs.

PMID- 30296301
TI  - Low frequency of asymptomatic dengue virus-infected donors in blood donor centers
      during the largest dengue outbreak in Taiwan.
AB  - To determine the prevalence of asymptomatic dengue virus-infected blood donors
      during the largest dengue outbreak in Taiwan history occurred in 2015, we
      examined the evidence of dengue virus (DENV) infection by the detection of DENV
      RNA genome using real-time reverse transcription-polymerase chain reaction (real
      time RT-PCR), DENV NS1 antigen using rapid diagnosis test (RDT) and anti-dengue
      antibody using IgM/IgG capture enzyme-linked immunosorbent assay (capture ELISA)
      and RDT in eight thousand serum samples from blood donations to the blood centers
      of the Taiwan Blood Services Foundation (TBSF) in Kaohsiung City and Tainan City
      during the largest dengue outbreak in Taiwan history occurred in 2015. Only one
      serum sample was positive for DENV RNA detection by using dengue-specific real
      time RT-PCR, the virus was DENV-2 determined by serotype-specific real-time RT
      PCR and sequencing, and the DENVs in the serum were confirmed as being infectious
      by a plaque assay. The recipient of this blood did not develop any dengue fever
      symptom on follow-up. None of the samples was NS1 RDT-reactive. Seventeen IgM
      positive samples were identified. There was a low prevalence of asymptomatic
      confirmed or probable DENV-infected blood donors in our study (0.013% and 0.21%,
      respectively), and no symptomatic transfusion-transmitted dengue (TT dengue) was
      developed during the largest dengue outbreak in Taiwan history in highly endemic
      areas and periods.

PMID- 30296303
TI  - Using a phiC31 "Disintegrase" to make new attP sites in the Drosophila genome at
      locations showing chromosomal position effects.
AB  - An engineered phiC31 "Disintegrase" able to make an attP site in Drosophila out
      of an attR-attL pair is described. This was used to generate attP sites at
      genomic locations where a mini-white (mini-w) transgene was subject to
      chromosomal position effects (CPE). The first step was random genomic integration
      of a P-element-based transposon with an insulated mini-w transgene. We then
      removed the upstream insulator using FLP recombinase to detect CPE. Next mini-w
      and the downstream insulator were "dis-integrated" leaving behind an attP site.
      The location is marked by a yellow+ transgene that is flanked by loxP sites, so
      it can also be removed. Using this system, we generated 10 new attP landing
      platforms. Three of these showing strong activating CPE were selected for further
      analysis. We show that the attP sites are functional by integrating in plasmids
      with attB sites. The CPE is recapitulated and can be blocked by insulators. We
      show that a dimerized 215 bp fragment of the 500 bp BEAF-dependent scs' insulator
      containing a high affinity BEAF binding site blocks the CPE, while a monomer of
      the sequence is less effective. This indicates that two BEAF binding sites make a
      stronger insulator than a single site. This system could be useful for generating
      attP sites at prescreened sites for other purposes, such as studying CPE in
      embryos or other tissues or for use with "trapped" enhancers of interest.

PMID- 30296302
TI  - Potent neutralizing antibodies in humans infected with zoonotic simian foamy
      viruses target conserved epitopes located in the dimorphic domain of the surface
      envelope protein.
AB  - Human diseases of zoonotic origin are a major public health problem. Simian foamy
      viruses (SFVs) are complex retroviruses which are currently spilling over to
      humans. Replication-competent SFVs persist over the lifetime of their human
      hosts, without spreading to secondary hosts, suggesting the presence of efficient
      immune control. Accordingly, we aimed to perform an in-depth characterization of
      neutralizing antibodies raised by humans infected with a zoonotic SFV. We
      quantified the neutralizing capacity of plasma samples from 58 SFV-infected
      hunters against primary zoonotic gorilla and chimpanzee SFV strains, and
      laboratory-adapted chimpanzee SFV. The genotype of the strain infecting each
      hunter was identified by direct sequencing of the env gene amplified from the
      buffy coat with genotype-specific primers. Foamy virus vector particles (FVV)
      enveloped by wild-type and chimeric gorilla SFV were used to map the envelope
      region targeted by antibodies. Here, we showed high titers of neutralizing
      antibodies in the plasma of most SFV-infected individuals. Neutralizing
      antibodies target the dimorphic portion of the envelope protein surface domain.
      Epitopes recognized by neutralizing antibodies have been conserved during the
      cospeciation of SFV with their nonhuman primate host. Greater neutralization
      breadth in plasma samples of SFV-infected humans was statistically associated
      with smaller SFV-related hematological changes. The neutralization patterns
      provide evidence for persistent expression of viral proteins and a high
      prevalence of coinfection. In conclusion, neutralizing antibodies raised against
      zoonotic SFV target immunodominant and conserved epitopes located in the receptor
      binding domain. These properties support their potential role in restricting the
      spread of SFV in the human population.

PMID- 30296304
TI  - Assessment of bleeding in patients with disseminated intravascular coagulation
      after receiving surgery and recombinant human soluble thrombomodulin: A cohort
      study using a database.
AB  - We aimed to investigate the incidence of bleeding-related adverse events (AEs)
      among patients with disseminated intravascular coagulation (DIC) receiving
      recombinant thrombomodulin (rTM) and those receiving other DIC treatments, the
      incidence by type of surgery, and the incidence when either blood transfusion or
      a hemostatic procedure was administered to treat DIC. In this cohort study, data
      were obtained from a large medical database (22 centers in Japan). The primary
      endpoint was the incidence rate of bleeding-related AEs by type of surgery. The
      secondary endpoint was the incidence rate of bleeding-related AEs based on
      whether blood transfusion or a hemostatic procedure was administered after the
      day of DIC treatment. In total, 4234 propensity score-matched patients were
      included in the main analysis (2117 patients each in the rTM and non-rTM groups).
      In the rTM and non-rTM groups, respectively, the incidence of bleeding-related
      AEs was 18.8% and 24.8% (p <0.001; risk ratio [RR] 0.757, 95% confidence interval
      [CI] 0.674-0.849), among patients requiring any type of surgery; 15.0% and 19.5%
      (p = 0.0001; RR 0.769, 95% CI 0.673-0.879) in patients requiring blood
      transfusion or a hemostatic procedure after the day of DIC treatment; 10.2% and
      11.6% (p = 0.4470; RR 0.879, 95% CI 0.630-1.226) in patients undergoing hepatic,
      biliary, or pancreatic surgery; 24.3% and 25.4% (p = 0.6439; RR 0.955, 95% CI
      0.786-1.160) in patients undergoing gastrointestinal surgeries; and 18.5% and
      30.1% (p = 0.0001; RR 0.614, 95% CI 0.481-0.782) in patients undergoing cardiac
      or cardiovascular surgery. Our findings suggest that rTM treatment for Japanese
      postsurgical patients who develop DIC was associated with significantly fewer
      bleeding-related AEs compared with those receiving other DIC treatments.

PMID- 30296305
TI  - CXCL4 contributes to host defense against acute Pseudomonas aeruginosa lung
      infection.
AB  - Platelets have been implicated in pulmonary inflammation following exposure to
      bacterial stimuli. The mechanisms involved in the platelet-mediated host response
      to respiratory bacterial infection remain incompletely understood. In this study,
      we demonstrate that platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4)
      plays critical roles in a mouse model of acute bacterial pneumonia using
      Pseudomonas aeruginosa. Platelets are activated during P. aeruginosa infection,
      and mice depleted of platelets display markedly increased mortality and impaired
      bacterial clearance. CXCL4 deficiency impairs bacterial clearance and lung
      epithelial permeability, which correlate with decreased neutrophil recruitment to
      BALF. Interestingly, CXCL4 deficiency selectively regulates chemokine production,
      suggesting that CXCL4 has an impact on other chemokine expression. In addition,
      CXCL4 deficiency reduces platelet-neutrophil interactions in blood following P.
      aeruginosa infection. Further studies revealed that platelet-derived CXCL4
      contributes to the P. aeruginosa-killing of neutrophils. Altogether, these
      findings demonstrate that CXCL4 is a vital chemokine that plays critical roles in
      bacterial clearance during P. aeruginosa infection through recruiting neutrophils
      to the lungs and intracellular bacterial killing.

PMID- 30296307
TI  - Renewable energy consumption and economic growth. Causality relationship in
      Central and Eastern European countries.
AB  - The new European model stipulates the achievement of an inclusive, sustainable
      and intelligent economic growth. Increasing the share of renewable energy is one
      of the factors that improve the quality of economic growth, similar to research,
      development and investment in human capital. In this paper we tested the
      correlation between economic growth and renewable energy consumption for ten
      European Union (EU) member states from Central and Eastern Europe (CEE) in the
      period 1990-2014, using Auto-regressive and Distributed Lag (ARDL) modeling
      procedure, a technique that captures causal relationships both on a short run and
      on a long run. The short run perspective reveals the transition towards a new
      energy paradigm, while the long run approach corresponds to the long-term
      equilibrium of the analyzed factors. Our results shows that, in the short run,
      the Gross Domestic Product (GDP) and Renewable Energy Consumption (REC) dynamics
      are independent in Romania and Bulgaria, while in Hungary, Lithuania and Slovenia
      an increasing renewable energy consumption improves the economic growth. The
      hypothesis of bi-directional causality between renewable energy consumption and
      economic growth is validated in the long run for both the whole group of analyzed
      countries as well as in the case of seven CEE states which were studied
      individually. These results allow us to look into the feasibility of the Europe
      2020 goals regarding the increase of energy efficiency and to propose public
      policies to achieve these goals.

PMID- 30296306
TI  - Estrogen and mechanical loading-related regulation of estrogen receptor-beta and
      apoptosis in tendinopathy.
AB  - Female-dominant tendinopathies are musculoskeletal disorders caused by repetitive
      hand posture and motion; they are considered overuse syndromes. Both external
      mechanical stress and changes in hormone levels might affect disease progression.
      We have previously reported that estrogen receptor-beta (ER)-beta expression was
      associated with the pathogenesis of de Quervain's disease. To study the
      underlying mechanisms, a cyclic stretching culture system was applied to tendon
      tissue from ovariectomized (OVX) rats. Furthermore, a collagenase I-induced rat
      tendinopathy model was established to examine the association of ER-beta with
      disease progression. Our results showed that ER-beta expression and the number of
      apoptotic cells were higher and associated with disease severity in rats with
      tendinopathy. Mechanical stress altered the morphology of primary tenocytes and
      collagen fiber alignment in tendons, and up-regulated the expression of matrix
      metalloproteinase-9, ER-beta, and interleukin-1beta, as well as induced apoptosis
      in tenocytes and tendon tissue from OVX rats. This is the first report on the
      effects of ER-beta and mechanical stress in tendinopathy. We hope these findings
      contribute to new pharmacological therapies targeting ER-beta signaling pathways
      to treat tendon-related diseases.

PMID- 30296310
TI  - Mycobacterium abscessus: A Rare Cause of Periprosthetic Knee Joint Infection.
AB  - A 61-year-old woman with a periprosthetic knee joint infection caused by
      Mycobacterium abscessus was successfully treated with surgical debridement,
      multidrug antimicrobial therapy, and staged reimplantation. To the authors'
      knowledge, this represents the first report of successfully treating this
      organism after knee arthroplasty. M. abscessus knee infections are rare, and
      there are no specific guidelines to inform treatment or successful treatment
      regimens for periprosthetic knee infections. Medical management alone was not
      successful in this case and hence cannot be recommended. Using a collaborative
      multidisciplinary approach, including surgical debridement, staged
      reimplantation, and multidrug antimicrobials, successful eradication of the
      periprosthetic joint infection caused by M. abscessus was achieved.

PMID- 30296309
TI  - 5 Points on Meniscal Allograft Transplantation.
AB  - Meniscus allograft transplantation (MAT) has yielded excellent long-term
      functional outcomes when performed in properly indicated patients. When
      evaluating a patient for potential MAT, it is imperative to evaluate past medical
      history and past surgical procedures. The ideal MAT candidate is a
      chronologically and physiologically young patient (<50 years) with symptomatic
      meniscal deficiency. Existing pathology in the knee needs to be carefully
      considered and issues such as malalignment, cartilage defects, and/or ligamentous
      instability may require a staged or concomitant procedure. Once an ideal
      candidate is identified, graft selection and preparation are critical steps to
      ensure a proper fit and long-term viability of the meniscus. When selecting the
      graft, accurate measurements must be taken, and this is most commonly performed
      using plain radiographs for this. Graft fixation can be accomplished by placing
      vertical mattress sutures and tying those down with the knee in full extension.

PMID- 30296308
TI  - A novel 3D printed mechanical actuator using centrifugal force for magnetic
      resonance elastography: Initial results in an anthropomorphic prostate phantom.
AB  - This work demonstrates a new method for the generation of mechanical shear wave
      during magnetic resonance elastography (MRE) that creates greater forces at
      higher vibrational frequencies as opposed to conventionally used pneumatic
      transducers. We developed an MR-compatible pneumatic turbine with an eccentric
      mass that creates a sinusoidal centrifugal force. The turbine was assessed with
      respect to its technical parameters and evaluated for MRE on a custom-made
      anthropomorphic prostate phantom. The silicone-based tissue-mimicking materials
      of the phantom were selected with regard to their complex shear moduli examined
      by rheometric testing. The tissue-mimicking materials closely matched human soft
      tissue elasticity values with a complex shear modulus ranging from 3.21 kPa to
      7.29 kPa. We acquired MRE images on this phantom at 3 T with actuation
      frequencies of 50, 60 Hz, 70 Hz, and 80 Hz. The turbine generated vibrational
      wave amplitudes sufficiently large to entirely penetrate the phantoms during the
      feasibility study. Increased wave length in the stiffer inclusions compared to
      softer background material were detected. Our initial results suggest that
      silicone-based phantoms are useful for the evaluation of elasticities during MRE.
      Furthermore, our turbine seems suitable for the mechanical assessment of soft
      tissue during MRE.

PMID- 30296311
TI  - A Three-View Radiographic Approach to Femoroacetabular Impingement.
AB  - Femoroacetabular impingement (FAI) is an abnormality of the hip joint that is
      increasingly being recognized as a cause of athletic disability and early
      degenerative hip disease. Despite significant advances in the knowledge of FAI,
      it remains a frequently unrecognized cause of hip pain in adolescents and young
      adults among orthopedic providers. The purpose of this article is to present a
      simple 3-view radiographic approach to young adults with hip pain. The
      radiographs include a standing anteroposterior view of the pelvis, a cross-table
      lateral view, and a false profile view. Good quality radiographs showing the
      common sites of potential impingement combined with a basic understanding of
      certain radiographic parameters may allow faster diagnosis, eliminate unnecessary
      studies, and allow earlier referral and management.

PMID- 30296133
TI  - Observation of Higgs Boson Decay to Bottom Quarks.
AB  - The observation of the standard model (SM) Higgs boson decay to a pair of bottom
      quarks is presented. The main contribution to this result is from processes in
      which Higgs bosons are produced in association with a W or Z boson (VH), and are
      searched for in final states including 0, 1, or 2 charged leptons and two
      identified bottom quark jets. The results from the measurement of these processes
      in a data sample recorded by the CMS experiment in 2017, comprising 41.3  fb^{-1}
      of proton-proton collisions at sqrt[s]=13  TeV, are described. When combined with
      previous VH measurements using data collected at sqrt[s]=7, 8, and 13 TeV, an
      excess of events is observed at m_{H}=125  GeV with a significance of 4.8
      standard deviations, where the expectation for the SM Higgs boson is 4.9. The
      corresponding measured signal strength is 1.01+/-0.22. The combination of this
      result with searches by the CMS experiment for H->bb[over -] in other production
      processes yields an observed (expected) significance of 5.6 (5.5) standard
      deviations and a signal strength of 1.04+/-0.20.

PMID- 30296312
TI  - Analysis of Incidence and Outcome Predictors for Patients Admitted to US
      Hospitals with Acetabular Fractures from 1990 to 2010.
AB  - The incidence of acetabular fractures and associated in-hospital complication
      rates in the United States are poorly defined. Studies evaluating predictors of
      outcome for isolated acetabular fractures are weakly generalizable due to small
      sample sizes or the inclusion of all types of pelvic fractures. This study sought
      to analyze trends in acetabular fractures and associated complications in the US
      using the largest and most recent national dataset available. The National
      Hospital Discharge Survey was queried to identify all patients admitted to US
      hospitals with acetabular fractures between 1990 and 2010. A representative
      cohort of 497,389 patients was identified, and multivariable logistic regression
      was used to identify independent predictors of mortality, adverse events,
      requirement of blood transfusion, and operative treatment with open reduction and
      internal fixation (ORIF). Between 1990 and 2010, the population-adjusted
      incidence of acetabular fractures increased from 7.8 to 9.5/100,000 capita (P <
      .001). Mortality declined from 5.9% to 0.4% (P < .001), paralleling an increase
      in the proportion of patients treated with ORIF (12.6%-20.4%, P < .001), which
      was the variable associated with the lowest odds of mortality. Surgical
      intervention was associated with higher odds of adverse events and a requirement
      for blood transfusion. The average in-hospital length of stay decreased from 17.0
      days to 10.3 days (P < .001). This study provides the largest and most
      comprehensive epidemiologic analysis of acetabular fractures in the US. Knowledge
      of the increasing incidence of acetabular fractures and prognostic factors
      associated with poor outcomes may improve outcomes.

PMID- 30296313
TI  - Arthroscopically-Guided, Cannulated, Headless Compression Screw Fixation of the
      Symptomatic Os Acromiale.
AB  - Os acromiale is a failure of fusion between 1 or more ossification centers of the
      scapula and the acromion process. Pain can be caused by motion and impingement of
      the unfused segment. Several methods for the management of os acromiale have been
      described. Internal fixation is the most common surgical technique, followed by
      excision and acromioplasty. We present a novel technique for treatment of
      symptomatic os acromiale using arthroscopically-guided headless compression
      screws. This is a viable technique in the management of symptomatic os acromiale
      due to preservation of the periosteal blood supply and less concern for
      symptomatic hardware.

PMID- 30296314
TI  - Complex Ankle and Hindfoot Arthrodesis Using Circular External Fixation.
AB  - Surgical reconstruction of the ankle and hindfoot in patients with diabetes,
      Charcot neuroarthropathy, osteomyelitis, deformity, and/or bone loss can be
      challenging and often results in amputation. In these patients, conventional
      internal fixation with plates, screws, and intramedullary nails is often not
      feasible because of ongoing infection or poor bone stock and soft tissue quality.
      The Ilizarov method of ankle and hindfoot arthrodesis is a well-established
      technique for limb reconstruction that uses circular external fixation to achieve
      solid bony fusion, optimal leg length, and eradication of infection in cases of
      complex pathology. This article discusses indications, contraindications, pearls,
      and pitfalls of performing ankle and hindfoot arthrodesis using the Ilizarov
      technique.

PMID- 30296315
TI  - Composite Fixation of Proximal Tibial Nonunions: A Technical Trick.
AB  - Nonunion after a proximal tibia fracture is often associated with poor bone
      stock, (previous) infection, and compromised soft tissues. These conditions make
      revision internal fixation with double plating difficult. Combining a plate and
      contralateral 2-pin external fixator, coined composite fixation, can provide an
      alternative means of obtaining stability without further compromising soft
      tissues. Three patients with a proximal tibia nonunion precluding standard
      internal fixation with double plating were treated with composite fixation. All 3
      patients achieved union with deformity correction at a mean of 5.2 months (range,
      5-5.5 months). The average range of motion (ROM) arc was 100 degrees  (range, 100
      degrees -115 degrees ) and postoperative ROM returned to pre-injury
      levels.Composite fixation can be a helpful adjunct in the treatment of this
      challenging problem.

PMID- 30296317
TI  - Reverse Total Shoulder Arthroplasty: Indications and Techniques Across the World.
AB  - Reverse total shoulder arthroplasty (RTSA) is a common treatment for rotator cuff
      tear arthropathy. We performed a systematic review of all the RTSA literature to
      answer if we are treating the same patients with RTSA, across the world. A
      systematic review was registered with PROSPERO, the international prospective
      register of systematic reviews, and performed with Preferred Reporting Items for
      Systematic reviews and Meta-Analyses (PRISMA) guidelines using 3 publicly
      available free databases. Therapeutic clinical outcome investigations reporting
      RTSA outcomes with levels of evidence I to IV were eligible for inclusion. All
      study, subject, and surgical technique demographics were analyzed and compared
      between continents. Statistical comparisons were conducted using linear
      regression, analysis of variance (ANOVA), Fisher's exact test, and Pearson's chi
      square test. There were 103 studies included in the analysis (8973 patients; 62%
      female; mean age, 70.9 +/- 6.7 years; mean length of follow-up, 34.3 +/- 19.3
      months) that had a low Modified Coleman Methodology Score (MCMS) (mean, 36.9 +/-
      8.7: poor). Most patients (60.8%) underwent RTSA for a diagnosis of rotator cuff
      arthropathy, whereas 1% underwent RTSA for fracture; indications varied by
      continent. There were no consistent reports of preopeartive or postoperative
      scores from studies in any region. Studies from North America reported
      significantly higher postoperative external rotation (34.1 degrees  +/- 13.3
      degrees  vs 19.3 degrees  +/- 8.9 degrees ) (P < .001) and a greater change in
      flexion (69.0 degrees  +/- 24.5 degrees  vs 56.3 degrees  +/- 11.3 degrees ) (P =
      .004) compared with studies from Europe. North America had the greatest total
      number of publications followed by Europe. The total yearly number of
      publications increased each year (P < .001), whereas the MCMS decreased each year
      (P = .037). The quantity, but not the quality of RTSA studies is increasing.
      Indications for RTSA varied by continent, although most patients underwent RTSA
      for rotator cuff arthropathy. The majority of patients undergoing RTSA are female
      over the age of 60 years for a diagnosis of rotator cuff arthropathy with
      pseudoparalysis.

PMID- 30296322
TI  - The Flint Lock: A Novel Technique in Total Knee Arthroplasty Closure.
AB  - Conventional interrupted sutures are traditionally used in extensor mechanism
      closure during total knee arthroplasty (TKA). In recent years, barbed suture has
      been introduced with the proposed benefits of decreased closure time and a
      watertight seal that is superior to interrupted sutures. Complication rates using
      barbed sutures and conventional interrupted sutures are similar. We propose a
      novel closure technique known as the Flint Lock, which is a double continuous
      interlocking stitch. The Flint Lock provides a quick and efficient closure to the
      extensor mechanism in TKA. In addition, similar to barbed suture, the Flint Lock
      should provide a superior watertight seal. It utilizes relatively inexpensive and
      readily available materials.

PMID- 30296316
TI  - Orthopedics in the Age of Accountable Care Organizations and Population Health:
      From Profit-Center to Cost-Center.

PMID- 30296319
TI  - The Cold, Hard Facts of Cryotherapy in Orthopedics.
AB  - Cryotherapy is the use of the anti-inflammatory and analgesic properties of ice
      to facilitate healing. Cryotherapy mediates these salutatory effects by reducing
      blood flow to the site of injury, down-regulating the production of inflammatory
      and pain-inducing prostaglandins, and diminishing the conductive ability of nerve
      endings. It is commonly used postoperatively in orthopedics to decrease analgesic
      requirements and blood loss as well as to increase range of motion, despite
      limited literature on its ability to produce such therapeutic effects in clinical
      practice. This article examines the available literature and the scientific
      evidence for the use and efficacy of cryotherapy in post-surgical orthopedic
      patients. It also reviews the potential pitfalls associated with improper use.
      Overall, this review seeks to provide insight into when, or whether, cryotherapy
      is appropriate for orthopedic patients during surgical recovery.

PMID- 30296321
TI  - The Effect of Insurance Type on Patient Access to Ankle Fracture Care Under the
      Affordable Care Act.
AB  - The purpose of this study is to assess the effect of insurance type (Medicaid,
      Medicare, private insurance) on the ability for patients with operative ankle
      fractures to access orthopedic traumatologists. The research team called 245
      board-certified orthopedic surgeons specializing in orthopedic trauma within 8
      representative states. The caller requested an appointment for their fictitious
      mother in order to be evaluated for an ankle fracture which was previously
      evaluated by her primary care physician and believed to require surgery. Each
      office was called 3 times to assess the response for each insurance type. For
      each call, information was documented regarding whether the patient was able to
      receive an appointment and the barriers the patient confronted to receive an
      appointment. Overall, 35.7% of offices scheduled an appointment for a patient
      with Medicaid, in comparison to 81.4%and 88.6% for Medicare and BlueCross,
      respectively (P < .0001). Medicaid patients confronted more barriers for
      receiving appointments. There was no statistically significant difference in
      access for Medicaid patients in states that had expanded Medicaid eligibility vs
      states that had not expanded Medicaid. Medicaid reimbursement for open reduction
      and internal fixation of an ankle fracture did not significantly correlate with
      appointment success rates or wait times. Despite the passage of the Affordable
      Care Act, patients with Medicaid have reduced access to orthopedic surgeons and
      more complex barriers to receiving appointments. A more robust strategy for
      increasing care-access for patients with Medicaid would be more equitable.

PMID- 30296320
TI  - The Effect of Age on the Benefits of Early Decompression for Cervical Spondylotic
      Myelopathy.
AB  - Cervical myelopathy is the most common cause of acquired spinal cord dysfunction
      in people aged >55 years. Advanced age and duration of symptoms have been
      implicated in the literature as negative prognostic indicators for postoperative
      functional improvement, but very few studies have evaluated the interaction of
      these factors. We retrospectively reviewed 125 patients who underwent surgery for
      cervical myelopathy. Patients were stratified according to age greater or less
      than 65 years and duration of symptoms of greater or less than 12 and 24 months.
      Functional outcomes were assessed using the Nurick score. Simple regression and
      multiple regression analyses were done, controlling for sex, preoperative Nurick
      score, surgical approach, smoking status, diabetes status, prior surgery, number
      of levels fused, ethanol use, and signal change on preoperative magnetic
      resonance imaging. The average change in Nurick score in all patients was 1.36,
      with a significant difference between patients with symptoms for <24 months and
      those with symptoms for >24 months (1.54 vs 0.98, P = .03). Multiple regression
      analysis revealed that older patients had a significant difference at 24 months
      (1.69 vs 1.25, P = .01), whereas younger patients showed slightly lower
      improvement overall and a change in Nurick score at both thresholds that was
      statistically nonsignificant.

PMID- 30296318
TI  - Subcutaneous Ulnar Nerve Transposition Using Osborne's Ligament as a
      Ligamentodermal or Ligamentofascial Sling.
AB  - The ulnar nerve is most commonly compressed at the elbow in the cubital tunnel.
      Conservative and operative treatments have been applied for cubital tunnel
      syndrome. Surgical management options include decompression, medial
      epicondylectomy, and various anterior transposition techniques. We describe a
      novel technique of anterior transposition of the ulnar nerve by using Osborne's
      ligament as a sling to avoid subluxation. Osborne's ligament is incised
      posteriorly and medially on the olecranon to create a sling with 2 to 3 cm width.
      The sling is tailored to wrap around the ulnar nerve and attached to the flexor
      pronator fascia or dermis to create a smooth gliding surface without causing
      compression. Ten patients with cubital tunnel syndrome, established by physical
      examination findings and electromyography/nerve conduction studies underwent
      ulnar nerve transposition using this technique and were able to participate in a
      phone survey. The average follow-up was 15.6 months (range, 4-28 months). The
      average time to become subjectively "better" after surgery was 4.2 weeks. The
      pain intensity was reduced from an average of 7.5 preoperatively to <1, on a 10
      point scale, at the time of the survey. All patients had symptomatic relief
      without any complication. The proposed technique using Osborne's ligament as a
      ligamentofascial or ligamentodermal sling offers a unique way of creating a non
      compressive sling with the component of the cubital tunnel itself and has an
      additional benefit of creating a smooth gliding surface for early return of
      function.

PMID- 30296325
TI  - Effect of NSAIDs on Pupil Diameter and Expression of Aqueous Humor Cytokines in
      FLACS Versus Conventional Phacoemulsification.
AB  - PURPOSE: To compare the concentrations of interleukin (IL) (IL-1b, IL-2, IL-4, IL
      5, IL-6, IL-8, IL-10, IL-12p70), interferon (IFN)-gamma, tumor necrosis factor
      (TNF)-alpha, and TNF-beta in the aqueous humor of patients undergoing femtosecond
      laser-assisted cataract surgery (FLACS) and corneal mechanical paracentesis
      treated with two different topical nonsteroidal anti-inflammatory drugs (NSAIDs):
      bromfenac and indomethacin. METHODS: In this prospective, randomized controlled,
      single-center study, aqueous humor samples were obtained immediately after
      performing the femtosecond laser procedure or at the start of conventional
      phacoemulsification. Preoperatively, the FLACS groups were administered (once
      daily and four times daily, respectively) either topical bromfenac 0.09% (12
      eyes) or indomethacin 0.1% (12 eyes). The corneal paracentesis bromfenac and
      indomethacin groups received the same regimen of instillation of NSAIDs,
      respectively. Quantitative analysis of the expressed cytokines in the aqueous
      humor was performed using FlowCytomix FC 500 Pro 3.0 Software (Bender MedSystems
      GmbH, Vienna, Austria). RESULTS: The intraoperative pupil diameter was correlated
      with the expression of IL-6 after the femtosecond laser procedure in the FLACS
      indomethacin group (r = -0.53; P = .07). A significant difference in mean
      pupillary size was detected between the FLACS bromfenac and indomethacin groups
      at the aspiration/irrigation time point (0.53 +/- 0.26 mm) and at the end of
      surgery (0.68 +/- 0.37 mm). Progressive pupillary constriction was observed in
      the indomethacin and bromfenac groups. CONCLUSIONS: A smaller expression of IL-6
      to the overall cytokine network value was observed in cases receiving
      preoperative bromfenac 0.09%, explaining improved maintenance of intraoperative
      mydriasis. [J Refract Surg. 2018;34(10):646-652.].

PMID- 30296324
TI  - Timing of Adverse Events Following Geriatric Hip Fracture Surgery: A Study of
      19,873 Patients in the American College of Surgeons National Surgical Quality
      Improvement Program.
AB  - This study uses a prospective surgical registry to characterize the timing of 10
      postoperative adverse events following geriatric hip fracture surgery. There were
      19,873 patients identified who were >=70 years undergoing surgery for hip
      fracture as part of the American College of Surgeons National Surgical Quality
      Improvement Program (ACS-NSQIP). The median postoperative day of diagnosis (and
      interquartile range) for myocardial infarction was 3 (1-5), cardiac arrest
      requiring cardiopulmonary resuscitation 3 (0-8), stroke 3 (1-10), pneumonia 4 (2
      10), pulmonary embolism 4 (2-11), urinary tract infection 7 (2-13), deep vein
      thrombosis 9 (4-16), sepsis 9 (4-18), mortality 11 (6-19), and surgical site
      infection 16 (11-22). For the earliest diagnosed adverse events, the rate of
      adverse events had diminished by postoperative day 30. For the later diagnosed
      adverse events, the rate of adverse events remained high at postoperative day 30.
      Findings help to enable more targeted clinical surveillance, inform patient
      counseling, and determine the duration of follow-up required to study specific
      adverse events effectively. Orthopedic surgeons should have the lowest threshold
      for testing for each adverse event during the time period of greatest risk.

PMID- 30296323
TI  - Time-to-Surgery for Definitive Fixation of Hip Fractures: A Look at Outcomes
      Based Upon Delay.
AB  - The morbidity and mortality after hip fracture in the elderly are influenced by
      non-modifiable comorbidities. Time-to-surgery is a modifiable factor that may
      play a role in postoperative morbidity. This study investigates the outcomes and
      complications in the elderly hip fracture surgery as a function of time-to
      surgery. Using the American College of Surgeons-National Surgical Quality
      Improvement Program data from 2011 to 2012, a study population was generated
      using the Current Procedural Terminology codes for percutaneous or open treatment
      of femoral neck fractures (27235, 27236) and fixation with a screw and side plate
      or intramedullary fixation (27244, 27245) for peritrochanteric fractures. Three
      time-to-surgery groups (<24 hours to surgical intervention, 24-48 hours, and >48
      hours) were created and matched for surgery type, sex, age, and American Society
      of Anesthesiologists class. Time-to-surgery was then studied for its effect on
      the post-surgical outcomes using the adjusted regression modeling. A study
      population of 6036 hip fractures was created, and 2012 patients were assigned to
      each matched time-to-surgery group. The unadjusted models showed that the earlier
      surgical intervention groups (<24 hours and 24-48 hours) exhibited a lower
      overall complication rate (P = .034) compared with the group waiting for surgery
      >48 hours. The unadjusted mortality rates increased with delay to surgical
      intervention (P = .039). Time-to-surgery caused no effect on the return to the
      operating room rate (P = .554) nor readmission rate (P = .285). Compared with
      other time-to-surgeries, the time-to-surgery of >48 hours was associated with
      prolonged total hospital length of stay (10.9 days) (P < .001) and a longer
      surgery-to-discharge time (hazard ratio, 95% confidence interval: 0.74, 0.69
      0.79) (P < .001). Adjusted analyses showed no time-to-surgery related difference
      in complications (P = .143) but presented an increase in the total length of stay
      (P < .001) and surgery-to-discharge time (P < .001). Timeliness of surgical
      intervention in a comorbidity-adjusted population of elderly hip fracture
      patients causes no effect on the overall complications, readmissions, nor 30-day
      mortality. However, time-to-surgery of >48 hours is associated with costly
      increase in the total length of stay, including an increased post-surgery-to
      discharge time.

PMID- 30296326
TI  - Implantable Collamer Lens(r) for Management of Pseudophakic Ametropia in Eyes
      With a Spectrum of Previous Corneal Surgery.
AB  - PURPOSE: To assess the visual outcomes, predictability, and safety of the
      Implantable Collamer Lens (ICL) (STAAR Surgical, Inc., Monrovia, CA) for the
      management of residual pseudophakic refractive error. METHODS: Forty-nine
      pseudophakic eyes of 40 patients in which myopic, hyperopic, or toric ICLs were
      implanted were retrospectively analyzed. Twenty-nine eyes had been implanted with
      a monofocal intraocular lens (IOL) and 20 eyes had a multifocal IOL. All IOLs
      were implanted in the capsular bag. Of the 49 eyes included, 6 had residual
      refractive error after phacoemulsification without corneal pathology or surgical
      alteration (virgin cornea group), 12 had LASIK or photorefractive keratectomy
      (PRK) (excimer laser group), 8 had radial keratotomy, 5 had intrastromal corneal
      ring segments (ICRS) implantation, 11 had penetrating keratoplasty, and 7 had
      deep anterior lamellar keratoplasty (DALK). Uncorrected and corrected (CDVA)
      distance visual acuity and manifest refraction were evaluated. RESULTS: The
      efficacy/safety indices were 0.92/1.10, 0.98/1.13, 1.04/1.11, 0.90/1.13,
      0.79/1.17, and 0.71/1.23 for the virgin cornea, excimer laser, radial keratotomy,
      ICRS, penetrating keratoplasty, and DALK groups, respectively. No eye lost one or
      more lines of CDVA. The virgin cornea, excimer laser, and radial keratotomy
      groups showed better predictability and accuracy, with 96.2% spherical equivalent
      within +/-1.00 diopters (D). The ICRS, penetrating keratoplasty, and DALK groups
      demonstrated approximately 50% spherical equivalent within +/-1.00 D. There were
      no intraoperative or postoperative complications. CONCLUSIONS: Good refractive
      outcomes and a strong safety record support the use of the ICL for the correction
      of residual refractive error in pseudophakic eyes with previous corneal surgery.
      [J Refract Surg. 2018;34(10):654-663.].

PMID- 30296327
TI  - Differences in Posterior Corneal Features Between Normal Corneas and Subclinical
      Keratoconus.
AB  - PURPOSE: To compare posterior corneal features and their discriminating power for
      differentiating normal corneas from subclinical keratoconus using the Placido
      dual-Scheimpflug analyzer. METHODS: Patients were retrospectively included in the
      study. The preoperative normal right eyes of 79 patients imaged with a Placido
      dual-Scheimpflug system and with a stable postoperative LASIK follow-up of a
      minimum of 36 months were included in the normal group and were compared to 39
      contralateral topographically normal eyes with clinically evident keratoconus in
      the fellow eye. The posterior surface variables measured were categorized
      according to the feature of the corneal shape they were characterizing
      (curvature, elevation, asymmetry, and eccentricity) and compared between the two
      groups using the Student's two-sample t test. The discriminating ability of the
      posterior surface variables was compared by receiver operator characteristics
      curves. RESULTS: Variables that related to asymmetry and elevation of the
      posterior surface were statistically significantly different between groups (P <
      .05), whereas eccentricity and curvature-related parameters were not. Receiver
      operator characteristics curves analysis showed that the maximum posterior
      elevation over the best-fit toric and aspheric surface reference shape had the
      highest discriminating ability for distinguishing normal corneas from subclinical
      keratoconus, with an area under the curve of 0.877, followed by the asphericity
      asymmetry index, with an area under the curve of 0.871, and posterior inferior
      superior value, with an area under the curve of 0.851. CONCLUSIONS: Posterior
      cornea measured with a dual-Scheimpflug analyzer provides useful parameters for
      differentiating normal corneas from subclinical keratoconus. Of the posterior
      surface parameters, asymmetry and elevation seem to be the most sensitive shape
      modifications for differentiating both populations. [J Refract Surg.
      2018;34(10):664-670.].

PMID- 30296328
TI  - Outcomes for Mixed Cylinder LASIK With the MEL 90(r) Excimer Laser.
AB  - PURPOSE: To report the outcomes of LASIK for mixed cylinder using the Triple-A
      ablation profile with the MEL 90 excimer laser (Carl Zeiss Meditec, Jena,
      Germany). METHODS: This was a retrospective analysis of all eyes treated by LASIK
      for mixed cylinder using the Triple-A ablation profile with the MEL 90 laser
      between July 2013 and October 2016. Patients were observed for 1 year after
      surgery. Standard outcomes analysis and vector analysis by the Alpins method were
      performed. RESULTS: The database review identified 105 eyes (82 patients) treated
      by LASIK for mixed cylinder using the MEL 90 laser. Mean age was 40 +/- 11 years
      (range: 18 to 65 years). Mean attempted spherical equivalent was +0.30 +/- 0.90
      diopters (D) (range: -2.30 to +1.75 D). Mean cylinder was -2.93 +/- 1.47 D
      (range: -0.75 to -7.00 D). Preoperative corrected distance visual acuity (CDVA)
      was 20/20 or better in 81% of eyes. Postoperative uncorrected distance visual
      acuity was 20/20 or better in 69% and 20/25 or better in 86% of eyes. Mean
      postoperative spherical equivalent relative to the intended target was -0.21 +/-
      0.38 D (range: -1.25 to +1.13 D), with 83% within +/-0.50 D. Mean postoperative
      cylinder was -0.57 +/- 0.41 D (range: 0.00 to -1.75 D). Geometric mean was 1.12
      for the correction index and 0.25 for the index of success. For angle of error,
      the arithmetic mean was -0.6 degrees  +/- 4.2 degrees  (range: -13.5 degrees  to
      9.5 degrees ) and the absolute mean was 2.9 degrees  +/- 3.0 degrees  (range: 0.0
      degrees  to 13.5 degrees ). There was loss of one line of CDVA in 3% of eyes and
      no eyes lost two or more lines CDVA. There was a small increase in contrast
      sensitivity after surgery at 3, 6, 12, and 18 cycles per degree (P < .05).
      CONCLUSIONS: One-year outcomes of LASIK using the MEL 90 laser for mixed cylinder
      up to -7.00 D demonstrated excellent efficacy, safety, and predictability. Vector
      analysis found a 12% overcorrection in magnitude of refractive cylinder. Given
      the high accuracy for angle of error, a nomogram could be applied to reduce the
      over-correction and further improve the uncorrected distance visual acuity
      outcomes. [J Refract Surg. 2018;34(10):672-680.].

PMID- 30296329
TI  - Sequential Customized Therapeutic Keratectomy for Reis-Bucklers' Corneal
      Dystrophy: Long-term Follow-up.
AB  - PURPOSE: To report long-term outcomes of sequential customized therapeutic
      keratectomy for Reis-Bucklers' corneal dystrophy. METHODS: This was a
      retrospective review of 14 eyes of 8 patients with Reis-Bucklers' corneal
      dystrophy that underwent surgical peeling with a spatula of the epithelium and
      subepithelial membrane present in Reis-Bucklers' corneal dystrophy, with
      subsequent sequential customized therapeutic keratectomy featuring a multi-step
      approach with sequential, repeated customized excimer laser photoablations
      alternating with repeat intraoperative topographies to monitor and progressively
      reduce corneal irregularities. RESULTS: At the last follow-up of 5.09 +/- 4.67
      years (range: 0.29 to 12.87 years), mean corrected distance visual acuity
      improved from 20/50 (range: 20/630 to 20/30) to 20/25 (range: 20/20 to 20/40) (P
      < .01), whereas mean refraction changed from -0.29 +/- 1.91 diopters (D) sphere
      and -0.75 +/- 0.81 D cylinder preoperatively to 1.25 +/- 2.10 D sphere and -1.08
      +/- 0.53 D cylinder postoperatively. Mean central keratometry values changed
      minimally from 42.67 +/- 2.26 D preoperatively to 42.65 +/- 2.30 D
      postoperatively. Coma significantly decreased from 0.60 +/- 0.40 to 0.35 +/- 0.28
      MUm (P < .05), whereas total higher order aberrations, spherical aberration, and
      trefoil remained stable. No patient underwent corneal transplantation. Disease
      recurrence required re-treatment using the same protocol in 14.28% of eyes (n =
      2) for a mean of 5.86 +/- 0.31 years (range: 5.64 to 6.08 years) after initial
      surgery. CONCLUSIONS: Five years after sequential customized therapeutic
      keratectomy, most eyes with Reis-Bucklers' corneal dystrophy showed improved
      visual acuity, stable refraction, and improved or stable higher order
      aberrations. [J Refract Surg. 2018;34(10):682-688.].

PMID- 30296330
TI  - Outcomes of Simultaneous and Sequential Cross-linking With Excimer Laser Surface
      Ablation in Keratoconus.
AB  - PURPOSE: To evaluate the outcomes of simultaneous and sequential corneal
      crosslinking (CXL) and excimer laser surface ablation protocols in keratoconus.
      METHODS: A literature review was conducted using MEDLINE. The studies were
      divided into three groups: the sequential group included studies with CXL
      followed by excimer laser surface ablation later, the simultaneous group included
      simultaneous excimer laser surface ablation and CXL, and the no CXL group
      included excimer laser surface ablation only with no CXL. The data on change in
      logMAR uncorrected distance visual acuity (UDVA), spectacle corrected distance
      visual acuity (CDVA), change in spherical equivalent (SE) and refractive
      astigmatism, change in maximum keratometry (Kmax), complications, and safety and
      efficacy indices were presented for the latest follow-up visits in all groups.
      RESULTS: Twenty-one studies (3 = sequential; 11 = simultaneous, 7 = no CXL) were
      included. UDVA improved in all groups. CDVA improved more in the sequential
      group. SE change was greatest in the no CXL group and the refractive astigmatism
      reduced comparably in the sequential and no CXL groups but less in the
      simultaneous group. Kmax reduced in all groups. Only the sequential group showed
      no progression. Corneal haze was reported in 100%, 54.5%, and 57.1% studies,
      respectively. Safety and efficacy indices were 1.96 and 1.58, 1.41 +/- 0.32 and
      0.91 +/- 0.41, and 1 and 0.82, respectively. CONCLUSIONS: The sequential group
      showed greater improvement in CDVA, SE, and refractive astigmatism. Corneal haze
      was frequently reported in all protocols. Safety and efficacy indices were
      highest when CXL was performed before excimer laser and least when excimer laser
      was performed alone without CXL. [J Refract Surg. 2018;34(10):690-696.].

PMID- 30296331
TI  - Presbyopic Excimer Laser Ablation: A Review.
AB  - PURPOSE: To provide an overview of the efficacy and safety of available
      presbyopic excimer laser ablation profiles. METHODS: Literature review. RESULTS:
      Monovision with excimer laser traditionally applies near correction to the non
      dominant eye. Different excimer laser presbyopic approaches include the increase
      in depth of focus, through the controlled change of spherical aberration or
      asphericity, or multifocal ablation patterns with central or peripheral near
      vision zones. The studies investigating different excimer laser ablation patterns
      applied in previously myopic eyes revealed high levels of efficacy with all
      ablation profiles (between 68% and 99% achieving binocular uncorrected distance
      visual acuity [UDVA] of 20/25 or better, and between 70% and 100% achieving
      uncorrected near visual acuity [UNVA] presenting J3 or better). In hypermetropic
      eyes, most of the studies revealed high levels of efficacy with different
      platforms (between 78% and 100% achieving binocular UDVA of 20/25 or better and
      between 70% and 100% achieving UNVA presenting J3 or better). Loss of two or more
      lines of corrected distance visual acuity varied between 0% and 10% in the myopic
      eyes and between 0% and 14% in the hyperopic eyes. CONCLUSIONS: There is evidence
      that excimer laser presbyopic strategies accomplish spectacle independence at
      reasonable levels. There are reliable and safe options for both myopic and
      hyperopic eyes with satisfactory outcomes regarding near and distance vision. [J
      Refract Surg. 2018;34(10):698-710.].

PMID- 30296332
TI  - Femtosecond Laser-Assisted Capsulotomy Markings for the Alignment of Toric IOLs:
      A New Technique.

PMID- 30296333
TI  - The postnatal development of ultrasonic vocalization-associated breathing is
      altered in glycine transporter 2-deficient mice.
AB  - KEY POINTS: Newborn mice produce ultrasonic vocalization to communicate with
      their mother. The neuronal glycine transporter (GlyT2) is required for efficient
      loading of synaptic vesicles in glycinergic neurons. Mice lacking GlyT2 develop a
      phenotype that resembles human hyperekplexia and the mice die in the second
      postnatal week. In the present study, we show that GlyT2-knockout mice do not
      acquire adult ultrasonic vocalization-associated breathing patterns. Despite the
      strong impairment of glycinergic inhibition, they can produce sufficient
      expiratory airflow to produce ultrasonic vocalization. Because mouse ultrasonic
      vocalization is a valuable read-out in translational research, these data are
      highly relevant for a broad range of research fields. ABSTRACT: Mouse models are
      instrumental with respect to determining the genetic basis and neural foundations
      of breathing regulation. To test the hypothesis that glycinergic synaptic
      inhibition is required for normal breathing and proper post-inspiratory activity,
      we analysed breathing and ultrasonic vocalization (USV) patterns in neonatal mice
      lacking the neuronal glycine transporter (GlyT2). GlyT2-knockout (KO) mice have a
      profound reduction of glycinergic synaptic currents already at birth, develop a
      severe motor phenotype and survive only until the second postnatal week. At this
      stage, GlyT2-KO mice are smaller, have a reduced respiratory rate and still
      display a neonatal breathing pattern with active expiration for the production of
      USV. By contrast, wild-type mice acquire different USV-associated breathing
      patterns that depend on post-inspiratory control of air flow. Nonetheless, USVs
      per se remain largely indistinguishable between both genotypes. We conclude that
      GlyT2-KO mice, despite the strong impairment of glycinergic inhibition, can
      produce sufficient expiratory airflow to produce ultrasonic vocalization.

PMID- 30296334
TI  - Periodontal disease increases the risk for onset of systemic comorbidities in
      dental hospital attendees: An 18-year retrospective cohort study.
AB  - BACKGROUND: Periodontal disease closely links to various systemic diseases. This
      l8-year retrospective cohort study investigated whether poor periodontal
      condition may increase the risk for onset of systemic comorbidities. METHODS: A
      total of 488 individual dental folders from 17 400 dental hospital attendees
      registered from 1996 to 1998 were randomly selected, and these participants were
      free of diabetes, cardiovascular disease, chronic obstructive pulmonary disease,
      cancer, stroke, cognitive impairment, hypertension, and dyslipidemia in the
      Clinical Management System. The records of periodontal examination and
      orthopantomogram on the first registration were obtained, and full-mouth bone
      level (BL) was measured. Onsets of the eight comorbidities concerned above until
      2016 were retrieved from the system. RESULTS: The participants with worse
      periodontal status on their first registration had significantly higher numbers
      of the eight comorbidities/mortality during the 18-year follow-ups than their
      counterparts (P < 0.05). BL presented as bone loss/age was independently
      correlated to the comorbidity profiles in two multivariate models (0 to 1 versus
      >=2; 0 to 2 versus >=3) after adjusting for age and sex (odds ratio [OR] = 1.87;
      OR = 2.18, P < 0.05), highlighting that the individuals with more bone resorption
      exhibited a greater number of the comorbidities as compared with their
      counterparts. Moreover, those with onsets of more comorbidities showed worse
      periodontal conditions according to four parameters employed (community
      periodontal index, BL, bone loss/age and number of remaining teeth) (P < 0.05).
      CONCLUSION: Within the limitations of this 18-year retrospective cohort study,
      our findings provide the first evidence that periodontal disease experience to
      some extent reflects the host susceptibility to onset of common systemic
      comorbidities. Further studies with larger sample sizes and appropriate
      adjustment of critical confounders are highly warranted to substantiate the
      current observation.

PMID- 30296335
TI  - An Unusually High Cocaine Blood Concentration in an Impaired Driving
      Investigation.
AB  - Cocaine is an illicit drug frequently encountered by forensic practitioners in
      driving under the influence of drugs (DUID) casework. Whole blood collected from
      a suspected drugged driver was found to contain 3.000 mg/L cocaine, 1.600 mg/L
      benzoylecgonine, and 0.260 mg/L methamphetamine. The high concentration of
      cocaine, while common in overdose death investigations, is unusual for an
      impaired driving case. Information from the officer revealed that the motorist
      swallowed cocaine during the traffic stop. Although a cocaine DUID charge could
      not be pursued, the blood methamphetamine concentration exceeded the State of
      Nevada "per se" limit for operating a motor vehicle. The motorist was
      successfully prosecuted for DUID based on his admission of using methamphetamine
      prior to driving and the blood methamphetamine result. This case highlights the
      importance of considering case history when interpreting laboratory results and
      the application of jurisdictional statutes as an approach to prosecuting
      suspected drug-impaired drivers.

PMID- 30296336
TI  - Effect of Relocation on Neuropsychiatric Symptoms in Elderly Adults Living in
      Long-Term Care.
AB  - OBJECTIVES: To determine the evolution of behavioral and psychiatric symptoms of
      dementia (BPSD) in nursing home (NH) residents after an environmental change
      through a relocation to a more architecturally suitable facility, while
      conserving the same medical staff. DESIGN: Prospective, single arm study.
      SETTING: Long-term care unit. PARTICIPANTS: NH residents (N=116; median age 82.3,
      range 75.5-89.2; median Neuropsychiatric Inventory for the Nursing Home (NPI/NH)
      score 22, range 11-34.5; 66.3% female), of whom 102 lived in regular units and 14
      in specialized care units (SCUs). MEASUREMENTS: Neuropsychiatric symptoms were
      evaluated as part of a comprehensive geriatric assessment for each resident 1
      week before the relocation and 3 times after the relocation (1, 4, 12 weeks)
      using the NPI/NH. RESULTS: A mixed-effect linear model found no significant
      change in global NPI/NH score in the regular unit and a significant decrease in
      overall NPI/NH score 4 weeks after relocation in the SCUs (beta-coefficient for
      time by SCU=-11.5, 95% confidence interval (CI)=-17.9-5.2, p < .001), reaching a
      total decrease of 13 points by 12 weeks after relocation (beta-coefficient for
      time by SCU=-12.8, 95% CI=-19.1-6.4, p < .001). A statistically significant
      decrease of 3 points for disinhibition, apathy, and agitation accompanied the
      NPI/NH score in the secured unit. An increase of 3 points in aberrant motor
      behavior was seen by 12 weeks after relocation in the SCU. CONCLUSION: Relocation
      to an architecturally different facility significantly reduced BPSD of NH
      residents 1 month after relocation. J Am Geriatr Soc 66:2183-2187, 2018.

PMID- 30296337
TI  - Cancer and Aging: Reflections for Elders (CARE): A pilot randomized controlled
      trial of a psychotherapy intervention for older adults with cancer.
AB  - OBJECTIVE: Cancer and Aging: Reflections for Elders (CARE) is a novel, telephone
      delivered intervention designed to alleviate distress in older cancer patients.
      This pilot randomized controlled trial tested the feasibility and initial
      efficacy of CARE, drawing from age-appropriate developmental themes and well
      established coping theory. METHOD: Eligible patients were >=70 years old; >=6
      months post-diagnosis of lung, prostate, breast, lymphoma, or gynecological
      cancer; on active cancer treatment or within 6 months of ending cancer treatment;
      and had elevated scores on the Distress Thermometer (>=4) or Hospital Anxiety and
      Depression Scale (>=6). Participants completed five sessions of psychotherapy
      over 7 weeks with assessments at study entry, post-intervention, and 2 months
      post-intervention. Primary outcomes were feasibility and initial efficacy on
      anxiety and depression; secondary outcomes included demoralization, coping,
      loneliness, and spiritual well-being. RESULTS: Fifty-nine participants were
      randomized to either the CARE arm (n = 31) or the enhanced Social Work Control
      arm (n = 28). The intervention was feasible and tolerable, meeting a priori
      criteria for rates of eligibility, acceptance, retention, assessment, and
      treatment fidelity. Upon completion of the intervention, participants in the CARE
      arm demonstrated lower mean depression scores (d = 0.58 [CI: 0.04-1.12], P =
      0.01) and trended towards increased coping-planning (d = 0.30 [CI: -0.83 to
      0.24], P = 0.18). Promising trends in anxiety (d = 0.41 [CI: -0.17 to 0.98], P =
      0.10) emerged at 2 months post-intervention; effects for coping-planning
      dissipated. CONCLUSION: These pilot data suggest the CARE intervention is
      feasibly delivered, potentially impacts important psychosocial variables, and is
      accessible for older, frail patients with cancer. Future research will evaluate
      this intervention on a larger scale.

PMID- 30296338
TI  - JAG2 signaling induces differentiation of CD14+ monocytes into Langerhans cell
      histiocytosis-like cells.
AB  - Langerhans cell histiocytosis (LCH) is a MAPK pathway-driven disease
      characterized by the accumulation of CD1a+ langerin+ cells of unknown origin. We
      have previously reported that the Notch signaling pathway is active in LCH
      lesions and that the Notch ligand Jagged2 (JAG2) induces CD1a and langerin
      expression in monocytes in vitro. Here we show that Notch signaling induces
      monocytes to acquire an LCH gene signature and that Notch inhibition suppresses
      the LCH phenotype. In contrast, while also CD1c+ dendritic cells or IL-4
      stimulated CD14+ monocytes acquire CD1a and langerin positivity in culture, their
      gene expression profiles and surface phenotypes are more different from primary
      LCH cells. We propose a model where CD14+ monocytes serve as LCH cell precursor
      and JAG2-mediated activation of the Notch signaling pathway initiates a
      differentiation of monocytes toward LCH cells in selected niches and thereby
      contributes to LCH pathogenesis.

PMID- 30296339
TI  - Status of Mandibular Third Molar Development as Evidence in Legal Age Threshold
      Cases.
AB  - The completion of the third molar roots has played an important role in
      ascertaining whether individuals may be at or over a legal threshold of age,
      often taken as 18 years. This study demonstrates that root apex completion in the
      third molar is relatively uninformative regarding the threshold of age 18 years
      in a sample of 1184 males, where mean age-of-attainment of root apex completion
      for third mandibular molars is about 19.4 years. This paper also considers the
      legal age threshold problem for cases where the third mandibular molar is not
      completely formed, and outlines the use of parametric models and Bayes' factors
      to evaluate dental evidence in statistically appropriate ways. It attempts to
      resolve confusion over age-within-stage versus age-of-attainment, likelihood
      ratios versus other diagnostic tests, and prior odds for a case versus the prior
      density for an age distribution.

PMID- 30296340
TI  - Modeling Undetected Live Poliovirus Circulation After Apparent Interruption of
      Transmission: Pakistan and Afghanistan.
AB  - Since most poliovirus infections occur with no paralytic symptoms, the
      possibility of silent circulation complicates the confirmation of the end of
      poliovirus transmission. Based on empirical field experience and theoretical
      modeling results, the Global Polio Eradication Initiative identified three years
      without observing paralytic cases from wild polioviruses with good acute flaccid
      paralysis surveillance as an indication of sufficient confidence that poliovirus
      circulation stopped. The complexities of real populations and the imperfect
      nature of real surveillance systems subsequently demonstrated the importance of
      specific modeling for areas at high risk of undetected circulation, resulting in
      varying periods of time required to obtain the same level of confidence about no
      undetected circulation. Using a poliovirus transmission model that accounts for
      variability in transmissibility and neurovirulence for different poliovirus
      serotypes and characterizes country-specific factors (e.g., vaccination and
      surveillance activities, demographics) related to wild and vaccine-derived
      poliovirus transmission in Pakistan and Afghanistan, we consider the probability
      of undetected poliovirus circulation for those countries once apparent die-out
      occurs (i.e., in the absence of any epidemiological signals). We find that gaps
      in poliovirus surveillance or reaching elimination with borderline sufficient
      population immunity could significantly increase the time to reach high
      confidence about interruption of live poliovirus transmission, such that the path
      taken to achieve and maintain poliovirus elimination matters. Pakistan and
      Afghanistan will need to sustain high-quality surveillance for polioviruses after
      apparent interruption of transmission and recognize that as efforts to identify
      cases or circulating live polioviruses decrease, the risks of undetected
      circulation increase and significantly delay the global polio endgame.

PMID- 30296341
TI  - Cholangiocyte-to-Hepatocyte Differentiation: a Context Dependent Process and an
      Opportunity for Regenerative Medicine.
AB  - The liver owns an extraordinary regenerative capacity to compensate functional
      mass loss after acute cytotoxic injury or surgical resection. Hepatic mass
      restoration following hepatocellular or cholangiocellular injury is commonly
      mediated by the proliferation and replenishment of the existing differentiated
      hepatocytes and biliary epithelial cells (BECs or cholangiocytes), respectively.
      However, during chronic hepatocellular damage, the long-term cell renewal
      capacity of differentiated hepatocytes becomes compromised. This article is
      protected by copyright. All rights reserved.

PMID- 30296342
TI  - Postoperative Delirium in Individuals Undergoing Transcatheter Aortic Valve
      Replacement: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: To evaluate the incidence of in-hospital postoperative delirium
      (IHPOD) after transcatheter aortic valve replacement (TAVR). DESIGN: Systematic
      review and meta-analysis. SETTING: Elective procedures PARTICIPANTS: Individuals
      undergoing TAVR. MEASUREMENTS: A literature search was conducted in PubMed,
      Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of
      Controlled Trials (up to December 2017). All observational studies reporting the
      incidence of IHPOD after TAVR (sample size > 25) were included in our meta
      analysis. The reported incidence rates were weighted to obtain a pooled estimate
      rate with 95% confidence interval (CI). RESULTS: Of 96 potentially relevant
      articles, 31 with a total of 32,389 individuals who underwent TAVR were included
      in the meta-analysis. The crude incidence of IHPOD after TAVR ranged from 0% to
      44.6% in included studies, with a pooled estimate rate of 8.1% (95% CI=6.7-9.4%);
      heterogeneity was high (Q = 449; I = 93%; pheterogeneity  < .001). The pooled
      estimate rate of IHPOD was 7.2% (95% CI=5.4-9.1%) after transfemoral (TF) TAVR
      and 21.4% (95% CI=10.3-32.5%) after non-TF TAVR. CONCLUSION: Delirium occurs
      frequently after TAVR and is more common after non-TF than TF procedures.
      Recommendations are made with the aim of standardizing future research to reduce
      heterogeneity between studies on this important healthcare problem.

PMID- 30296343
TI  - Fluoxetine-induced Stevens-Johnson syndrome and liver injury.
AB  - WHAT IS KNOWN AND OBJECTIVE: Drug-induced liver injuries (DILI) are overall rare
      and often associated with use of medications. Medications are also the most
      common aetiology of Stevens-Johnson syndrome (SJS), but SJS is seldom seen
      concomitantly with liver injury. Many common drugs can cause either one of these
      conditions; however, there are no reported cases of concomitant DILI and SJS
      secondary to fluoxetine. CASE SUMMARY: A 41-year-old female presented with a skin
      rash and abnormal liver function tests after the recent initiation of fluoxetine.
      Skin and liver biopsies showed features of SJS and DILI, respectively. Fluoxetine
      was stopped, following which there was improvement in her liver function tests
      and skin rash, without progression to fulminant hepatic failure. WHAT IS NEW AND
      CONCLUSION: Commonly used and safe pharmaceuticals such as fluoxetine have the
      potential for serious adverse events affecting the skin and liver.

PMID- 30296344
TI  - A Preliminary Investigation into the Accuracy of 3D Modeling and 3D Printing in
      Forensic Anthropology Evidence Reconstruction.
AB  - There is currently no published empirical evidence-base demonstrating 3D printing
      to be an accurate and reliable tool in forensic anthropology, despite 3D printed
      replicas being exhibited as demonstrative evidence in court. In this study, human
      bones (n = 3) scanned using computed tomography were reconstructed as virtual 3D
      models (n = 6), and 3D printed using six commercially available printers, with
      osteometric data recorded at each stage. Virtual models and 3D prints were on
      average accurate to the source bones, with mean differences from -0.4 to 1.2 mm (
      0.4% to 12.0%). Interobserver differences ranged from -5.1 to 0.7 mm (-5.3% to
      0.7%). Reconstruction and modeling parameters influenced accuracy, and prints
      produced using selective laser sintering (SLS) were most consistently accurate.
      This preliminary investigation into virtual modeling and 3D printer capability
      provides a novel insight into the accuracy of 3D printing osteological samples
      and begins to establish an evidence-base for validating 3D printed bones as
      demonstrative evidence.

PMID- 30296345
TI  - Mapping Socioeconomic Exposure for Flood Risk Assessment in Italy.
AB  - Detailed spatial representation of socioeconomic exposure and the related
      vulnerability to natural hazards has the potential to improve the quality and
      reliability of risk assessment outputs. We apply a spatially weighted dasymetric
      approach based on multiple ancillary data to downscale important socioeconomic
      variables and produce a grid data set for Italy that contains multilayered
      information about physical exposure, population, gross domestic product, and
      social vulnerability. We test the performances of our dasymetric approach
      compared to other spatial interpolation methods. Next, we combine the grid data
      set with flood hazard estimates to exemplify an application for the purpose of
      risk assessment.

PMID- 30296346
TI  - Do sexual calls in female black capuchin monkeys (Sapajus nigritus) vary with
      fertility? An acoustic analysis.
AB  - Females across a range of animal taxa produce vocalizations and signals uniquely
      associated with periods of mating. While such signals may ultimately function to
      increase female attractivity to males, conflicting findings challenge the extent
      to which these signals co-vary in accordance with the probability of conception.
      Female black capuchin monkeys (Sapajus nigritus) display an elaborate repertoire
      of both vocal and visual components as part of their socio-sexual behavior, and
      previous analyses have shown that the rates of production of visual, but not
      vocal, components provide graded information on female ovulation. It remains
      possible, however, that the acoustic parameters of these sexual calls, rather
      than their rate of productions, co-vary with female fertility. To test this, we
      analyzed structural and temporal call parameters from estrous calls and post
      copulatory calls recorded over five consecutive mating seasons in 12 sexually
      mature females at Iguazu National Park, Argentina. Calls given during the fertile
      phase of the female ovarian cycle were compared with those given during the non
      fertile phase, as determined by profiles of female reproductive hormones.
      Similarly, within the fertile phase, we tested whether temporal or spectral
      acoustic parameters of calls gradually change with the approach of ovulation. We
      did not find any significant relationship between call parameters and the two
      measures of female fertility in either female estrous calls or post-copulatory
      calls. However, some differences between pre- and post-copulatory calls were
      apparent. Overall, our results indicate that sexual calls in black capuchin
      females do not provide precise information about the timing of ovulation, but may
      allow listeners to make probabilistic inferences about whether copulations have
      taken place. This, combined with previous findings, suggests that females in our
      study may use signals in different modalities to convey information about their
      fertility and sexual behavior with varying degrees of precision.

PMID- 30296347
TI  - Electrochemical Synthesis of 5-Aryl-phenanthridin-6-one by Dehydrogenative N,C
      Bond Formation.
AB  - Currently, the general synthesis of 5-aryl-phenanthridin-6-ones relies on the
      involvement of metal catalysis. Despite the urgent demand for green alternatives,
      avoiding synthetic routes that require transition metals for key roles is still
      challenging. Electrochemical efforts employing a constant potential protocol in
      divided cells revealed a possible alternative to the catalytic approach. A
      constant current protocol, undivided cells, and a remarkably low supporting
      electrolyte concentration enable a novel access to N-aryl-phenanthridin-6-ones by
      anodic N,C bond formation using directly generated amidyl radicals. Easy
      accessible starting materials, a broad scope of applicable functional groups,
      good yields, and a very simple set-up are the benefits of this sustainable
      method.

PMID- 30296348
TI  - Guardian of mitochondrial function: an expanded role of Parkin in skeletal
      muscle.

PMID- 30296349
TI  - Visible-Light-Driven, Copper-Catalyzed Decarboxylative C(sp3 )-H Alkylation of
      Glycine and Peptides.
AB  - Despite a well-developed and growing body of work in Cu catalysis, the potential
      of Cu to serve as a photocatalyst remains underexplored. Reported herein is the
      first example of visible-light-induced Cu-catalyzed decarboxylative C(sp3 )-H
      alkylation of glycine for preparing alpha-alkylated unnatural alpha-amino acids.
      It merits mentioning that the mild conditions and the good functional-group
      tolerance allow the modification of peptides using this method. The mechanistic
      studies revealed that a radical-radical coupling pathway is involved in the
      reaction.

PMID- 30296350
TI  - Three-dimensional transesophageal echocardiography is an attractive alternative
      to cardiac multi-detector computed tomography for aortic annular sizing:
      Systematic review and meta-analysis.
AB  - BACKGROUND: Cardiac imaging is the cornerstone of the pretranscatheter aortic
      valve replacement (TAVR) assessment. Multi-detector computed tomography (MDCT) is
      considered the conventional imaging modality. However, there is still no
      definitive gold standard. Targeted cohort of inoperable high-risk patients with
      underlying comorbidities, particularly renal impairment, makes apparent the need
      for MDCT alternative. We aimed to demonstrate the correlation extent between MDCT
      and three-dimensional transesophageal echocardiography (3DTEE) aortic annular
      area measures and to answer the question: Is 3DTEE a good alternative to MDCT?
      METHODS: A systematic literature search and meta-analysis were conducted to
      evaluate the degree of correlation and agreement between 3DTEE and MDCT aortic
      annular sizing. A thorough assessment of EMBASE, PubMed, and Cochrane Central
      Register of Controlled Trials (CENTRAL) was performed. All studies comparing
      3DTEE and MDCT in relation to aortic annular sizing were included. RESULTS:
      Thirteen studies were included (N = 1228 patients). A strong linear correlation
      was found between 3DTEE and MDCT measurements of aortic annulus area (r = 0.84, P
      < 0.001), mean perimeter (r = 0. 0.85, P < 0.001), and mean diameter (r = 0.80, P
      < 0.001). Bland-Altman plots revealed smaller mean 3DTEE values in comparison to
      MDCT for aortic annular area, the mean difference being -2.22 mm2 with 95% limits
      of agreement -12.79 to 8.36. CONCLUSION: Aortic annulus measurements obtained by
      3DTEE demonstrated a high level of correlation with those evaluated by MDCT. This
      makes 3DTEE a feasible choice for aortic annulus assessment, with advantage of
      real time assessment, lack of contrast, and no radiation exposure.

PMID- 30296351
TI  - Variable position of esophagus, a conundrum for blind transesophageal probe
      insertion.

PMID- 30296352
TI  - Interband Electron Pairing for Superconductivity from the Breakdown of the Born
      Oppenheimer Approximation.
AB  - The origin of interband electron pairing, responsible for enhancing
      superconductivity, and the factors controlling its strength were examined. We
      show that interband electron pairing is a natural consequence of breaking down
      the Born-Oppenheimer approximation during electron-phonon interactions. Its
      strength is determined by the pair-state excitations around the Fermi surfaces
      that take place to form a superconducting state. Fermi surfaces favorable for the
      pairing were found, and the implications of this observation are discussed.

PMID- 30296353
TI  - Low dose isotretinoin for pigmented post-varicella scars.

PMID- 30296354
TI  - Study on bone quality in the human mandible-Alignment of biological apatite
      crystallites.
AB  - The importance of considering bone quality during oral implant treatment is
      increasingly being recognized. Assessment of bone quality in response to changes
      in the jaw bone is extremely important when planning treatment. The present study
      analyzed biological apatite (BAp) crystallites, a bone quality factor, in order
      to investigate crystallographic anisotropy in dentate and edentulous human
      mandibles. Using mandibular samples from Japanese adult cadavers, a region of
      interest was established comprising cortical bone in the central incisors.
      Samples were classified into five morphological categories based on the extent of
      bone resorption. Bone mineral density (BMD) was measured and diffraction
      intensity ratios were calculated using a microbeam X-ray diffraction system.
      While no differences were observed in BMD, differences were observed in BAp
      crystallite alignment between the measurement points. In the alveolar region,
      samples with residual alveolar bone showed strong alignment in the occlusal
      direction, while samples with marked alveolar bone resorption had preferential
      alignment in the mesiodistal direction. The present findings suggest that tooth
      loss and the extent of alveolar bone resorption affects bone quality in the
      mandible. (c) 2018 Wiley Periodicals, Inc. J. Biomed. Mater. Res. Part B: 2018.

PMID- 30296355
TI  - Autofluorescence lifetime imaging of cellular metabolism: Sensitivity toward cell
      density, pH, intracellular, and intercellular heterogeneity.
AB  - Autofluorescence imaging (AFI) has greatly accelerated in the last decade, way
      past its origins in detecting endogenous signals in biological tissues to
      identify differences between samples. There are many endogenous fluorescence
      sources of contrast but the most robust and widely utilized have been those
      associated with metabolism. The intrinsically fluorescent metabolic cofactors
      nicotinamide adenine dinucleotide (NAD+ /NADH) and flavin adenine dinucleotide
      (FAD/FADH2 ) have been utilized in a number of AFI applications including basic
      research, clinical, and pharmaceutical studies. Fluorescence lifetime imaging
      microscopy (FLIM) has emerged as one of the more powerful AFI tools for NADH and
      FAD characterization due to its unique ability to noninvasively detect metabolite
      bound and free states and quantitate cellular redox ratio. However, despite this
      widespread biological use, many standardization methods are still needed to
      extend FLIM-based AFI into a fully robust research and clinical diagnostic tools.
      FLIM is sensitive to a wide range of factors in the fluorophore microenvironment,
      and there are a number of analysis variables as well. To this end, there has been
      an emphasis on developing imaging standards and ways to make the image
      acquisition and analysis more consistent. However, biological conditions during
      FLIM-based AFI imaging are rarely considered as key sources of FLIM variability.
      Here, we present several experimental factors with supporting data of the
      cellular microenvironment such as confluency, pH, inter-/intracellular
      heterogeneity, and choice of cell line that need to be considered for accurate
      quantitative FLIM-based AFI measurement of cellular metabolism. (c) 2018
      International Society for Advancement of Cytometry.

PMID- 30296356
TI  - Large scale segmental bone defect healing through the combined delivery of VEGF
      and BMP-2 from biofunctionalized cortical allografts.
AB  - Large scale cortical allografts suffer from poor incorporation and healing and
      often end in graft failure 5-10 years after implantation. To reduce these
      failures we have developed a growth-factor loaded cortical allograft capable of
      delivering one or two factors with a degree of temporal control and precision
      that permits the early release of one growth factor followed by the later and
      more sustained release of the other. We have loaded vascular endothelial growth
      factor (VEGF) and bone morphogenetic protein-2 (BMP-2), both critical components
      of bone formation and repair, onto cortical long bone allografts such that the
      VEGF is released first and followed shortly by BMP-2. Coated and factor-loaded
      allografts were placed into a critical sized rat femoral segmental defect and
      allowed to heal for either 4 or 8 weeks. Healing at each time point was compared
      to allografts loaded with only BMP-2 and allografts containing no growth factors.
      Results indicate statistically significant increases in new bone formation from 4
      to 8 weeks around allografts loaded with both VEGF and BMP-2 over allografts with
      no growth factor, suggesting that factor-loaded polymer-coated allografts
      delivering multiple factors with temporal precision may provide a new off-the
      shelf tool to the orthopedic surgeon for management of large-scale orthopedic
      bone defects. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: 2018.

PMID- 30296357
TI  - Are DNA damage response kinases a target for the differentiation treatment of
      acute myeloid leukemia?
AB  - Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy
      characterized by the expansion of hematopoietic stem/progenitor cells (HPCs)
      blocked at different stages of maturation/differentiation. The poor outcome of
      AMLs necessitates therapeutic improvement. In AML, genes encoding for myeloid
      transcription factors, signaling receptors regulating cell proliferation, and
      epigenetic modifiers can be mutated by somatically acquired genetic mutations or
      altered by chromosomal translocations. These mutations modify chromatin
      organization at genes sites regulating HPCs proliferation, terminal
      differentiation, and DNA repair, contributing to the development and progression
      of the disease. The reversibility of the epigenetic modifications by drug
      treatment makes epigenetic changes attractive targets for AML therapeutic
      intervention. Recent findings underline increased DNA damage and abnormalities in
      the DNA damage response (DDR) as a critical feature of AML blasts. The DDR
      preserves cell integrity and must be tightly coordinated with DNA methylation and
      chromatin remodeling to ensure the accessibility to the DNA of transcription
      factors and repair enzymes. A crucial role in these events is played by the
      ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related
      protein (ATR) kinases, which are hyperactive in AML. Based on these findings, we
      hypothesize the inhibition of DNA damage kinases as an alternative or
      complementary strategy for the differentiation treatment of AML as it leads to a
      reduced ability to repair the DNA damage, and to the inhibition of specific
      epigenetic modifiers whose function is altered in leukemic cells. (c) 2018 IUBMB
      Life, 70(11):1057-1066, 2018.

PMID- 30296358
TI  - Gingerenone A Sensitizes the Insulin Receptor and Increases Glucose Uptake by
      Inhibiting the Activity of p70 S6 Kinase.
AB  - SCOPE: The bioactive constituents in ginger extract are responsible for anti
      hyperglycemic effects and the underlying mechanisms are incompletely understood.
      Gingerenone A (Gin A) has been identified as an inhibitor of p70 S6 (S6K1), a
      kinase that plays a critical role in the pathogenesis of insulin resistance. This
      study aims to evaluate if Gin A can sensitize the insulin receptor by inhibiting
      S6K1 activity. METHODS AND RESULTS: Western blot analysis reveals that Gin A
      induces phosphatidylinositide-3 kinase (PI3K) feedback activation in murine 3T3
      L1 adipocytes and rat L6 myotubes, as evidenced by increased AKTS473 and S6K1T389
      but decreases S6S235/236 and insulin receptor substrate 1 (IRS-1)S1101
      phosphorylation. Western blot and immunoprecipitation analysis reveal that Gin A
      increases insulin receptor tyrosine phosphorylation in L6 myotubes and IRS-1
      binding to the PI3K in 3T3-L1 adipocytes. Confocal microscopy reveals that Gin A
      enhances insulin-induced translocation of glucose transporter 4 (GLUT4) into the
      cell membrane in L6 cells. 2-NBDG (2-N-(Nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2
      deoxyglucose) Fluorescent assay reveals that Gin A enhances insulin-stimulated
      glucose uptake in 3T3-L1 adipocytes and L6 myotubes. CONCLUSIONS: Gin A overcomes
      insulin resistance and increases glucose uptake by inhibiting S6K1 activity. Gin
      A or other plant-derived S6K1 inhibitors could be developed as novel antidiabetic
      agents.

PMID- 30296359
TI  - MCL1 Gene Silencing Promotes Senescence and Apoptosis of Glioma Cells via
      Inhibition of the PI3K/Akt Signaling Pathway.
AB  - Glioma is known to be the most prevalent primary brain tumor. In recent years,
      there has been evidence indicating myeloid cell leukemia-1 (MCL1) plays a role in
      brain glioblastoma. Therefore, the present study was conducted with aims of
      exploring the ability of MCL1 silencing to influence glioma cell senescence and
      apoptosis through the mediation of the phosphatidylinositol 3-kinase
      (PI3K)/protein kinase B (Akt) signaling pathway. Glioma and tumor-adjacent
      tissues were collected in order to detect the presence of higher levels of MCL1
      protein expression. Next, the mRNA and protein expression of MCL1, PI3K, Akt, B
      cell lymphoma 2 (Bcl2), Bcl2-associated X (Bax), B lymphoma Mo-MLV insertion
      region 1 homolog (Bmi-1), and phosphatase and tensin homolog (PTEN) were
      determined. Cell counting kit-8 assay was applied to detect cell proliferation,
      beta-galactosidase staining for cell senescence, and flow cytometry for cell
      cycle entry and apoptosis. Initially, the results revealed higher positive
      expression rate of MCL1 protein, increased mRNA and protein expression of MCL1,
      PI3K, Akt, Bmi-1, and Bcl-2 and decreased that of Bax and PTEN in human glioma
      tissues. The silencing of MCL1 resulted in a decrease in mRNA and protein
      expression of PI3K, Akt, Bmi-1, and Bcl-2 and an increase in Bax and PTEN
      expressions in glioma cells. Moreover, silencing of MCL1 also inhibited cell
      proliferation and cell cycle entry in glioma cells, and promoted glioma cell
      senescence and apoptosis. In conclusion, the aforementioned results collectively
      suggested that the silencing of MCL1 promotes senescence and apoptosis in glioma
      cells through inhibiting the PI3K/Akt signaling pathway. Thus, decreasing the
      expression of MCL1 might have therapeutic functions in glioma. (c) 2018 IUBMB
      Life, 2018.

PMID- 30296360
TI  - In vitro remineralization of artificial enamel caries with resin composites
      containing calcium phosphate particles.
AB  - The aim of the study was to evaluate the effect of experimental composites
      containing dicalcium phosphate dihydrate (DCPD) on remineralization of enamel
      lesions. Five resin-based composites containing equal parts (in mols) of
      bisphenol-A glycidyl dimethacrylate (BisGMA), triethylene glycol dimethacrylate
      (TEGDMA), and 60 vol % of fillers were manipulated. Filler phase was constituted
      by silanized barium glass and 0, 10, or 20 vol % of DPCD particles, either
      functionalized (F) or nonfunctionalized (NF) with TEGDMA. Artificial subsurface
      lesions were produced in human enamel fragments and divided according to the
      resin composite applied on the lesion (no DCPD, 20% NF, 20% F, 10% NF, 10% F)
      plus a group without composite build-up (nontreated, NT). Fragments were exposed
      to 16 days of pH cycling. Specimens were evaluated using transverse
      microradiography (TMR). Calcium and phosphate concentrations in pH-cycling
      solutions were determined by spectrophotometry. TMR and ionic concentrations were
      analyzed using one-way ANOVA/Tukey and Kruskal-Wallis/Dunn test, respectively
      (alpha: 0.05). All composite groups showed enamel remineralization (3%-23%).
      Higher mineral recovery in the middle (7%-11%) and bottom (2%-7%) thirds of the
      lesion was observed in groups with DCPD-containing composites compared to the "no
      DCPD" group (middle: 1%, bottom: -3%). Lesion depth was significantly reduced in
      groups using DCPD-containing composites compared to NT group. No noticeable
      increase in calcium and phosphate ions was observed in the pH-cycling solutions
      due to the presence of DCPD in the composites. In conclusion, composites with
      DCPD fractions as low as 10%, regardless of functionalization, were able to
      promote mineral recovery and reduce lesion depth of enamel lesions. (c) 2018
      Wiley Periodicals, Inc. J Biomed Mater Res B Part B, 2018.

PMID- 30296361
TI  - Preparation of self-regulating/anti-adhesive hydrogels and their ability to
      promote healing in burn wounds.
AB  - Few burn dressings can self-regulate the optimal humidity levels that are
      required for wound healing, while also providing good anti-adhesive properties to
      prevent damage that can occur when wound dressings are changed. Consequently, a
      water-soluble carboxymethylcellulose sodium/sodium alginate/chitosan (CMC
      Na/SA/CS) composite hydrogel has been developed as a potential burn wound
      dressing, with orthogonal testing revealing an optimal ratio of CMC-Na, SA, and
      CS as 2, 3, and 1 wt % for hydrogel preparation, respectively. The resultant
      hydrogel has been formulated into composite wound dressings that were then used
      for the treatment of deep second degree burn wounds in Sprague-Dawley (SD) rats.
      Analysis of the physical properties of this dressing revealed that it exhibits
      good water vapor permeability properties that promote the healing of deep second
      degree burn wounds. The pro-healing mechanism of the dressing has been
      investigated Vascular endothelial growth factor (VEGF) expression was upregulated
      and basic fibroblast growth factor (bFGF) expression was downregulated in the
      early periods of wound healing, with upregulation of bFGF then occurring at a
      later stage of wound healing. At the same time, the wound dressing decreased the
      levels of tumor necrosis factor-alpha and interleukin-6, thus validating its
      beneficial effect on the wound healing process at a biomolecular level. In
      conclusion, this new hydrogel dressing was shown to exhibit excellent self
      regulatory and anti-adhesive properties that synergistically promote the healing
      of burn wounds in rats, thus providing promising results that may have clinical
      applications. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B, 2018.

PMID- 30296363
TI  - High modulus hydrogels for ophthalmic and related biomedical applications.
AB  - This paper presents three families of semi-interpenetrating polymer network
      (SIPN) hydrogels based on an ester-based polyurethane (EBPU) and hydrophilic
      monomers: N,N-dimethylacrylamide (NNDMA), N-vinyl pyrrolidone (NVP) and
      acryloylmorpholine (AMO) as potential materials for keratoprosthesis,
      orthokeratology and mini-scleral lens application. Hydrogels sheets were
      synthesized via free-radical polymerization with methods developed in-house. SIPN
      hydrogels were characterized for their equilibrium water content, mechanical and
      surface properties. Three families of optically clear SIPN-based hydrogels have
      been synthesized in the presence of water with >10% of composition attributable
      to EBPU. Water contents of SIPN materials ranged from 30% to 70%. SIPNs with
      <=15% EBPU of total composition showed little influence to mechanical properties,
      whereas >15% EBPU contributed significantly to an increase in material stiffness.
      In the hydrated state, SIPNs with <=15% EBPU of total composition show little
      difference in polar component (gammap ) of surface free energy, whereas for >15%
      EBPU there is a decrease in gammap . The EBPU SIPN hydrogels display
      complementary material properties for keratoprosthesis, orthokeratology, and mini
      scleral applications. (c) 2018 The Authors. journal Of Biomedical Materials
      Research Part B: Applied Biomaterials Published By Wiley Periodicals, Inc. J
      Biomed Mater Res B Part B, 2018.

PMID- 30296362
TI  - Hypothalamic Obesity: 4 Years of the International Registry of Hypothalamic
      Obesity Disorders.
AB  - OBJECTIVE: Hypothalamic obesity (HyOb) is a rare cause of rapid weight gain and
      early metabolic comorbidities. Effective treatment strategies are limited. The
      registry collected participant data and compared treatment approaches. METHODS:
      The International Registry of Hypothalamic Obesity Disorders (IRHOD) was created
      as a registry portal to provide education. Data collected from the initial 4
      years were evaluated. RESULTS: Eighty-seven participants were included for
      analysis (median age: 27 years, range: 3-71 years). A total of 96.5% had obesity,
      and 3.5% had overweight at maximal weight. Seventy-five had brain tumors (86%)
      the majority were craniopharyngiomas (72% of those with tumors). Nontumor
      etiologies included congenital brain malformation (4.6%), traumatic brain injury
      (3.4%), and genetic anomaly (2.3%). Ninety percent received obesity treatments
      including nutritional counseling (82%), pharmacotherapy (59%), bariatric surgery
      (8%), and vagal nerve stimulation (1%). Forty-six percent reported follow-up BMI
      results after obesity treatment. Surgery was most effective (median BMI decrease:
      -8.2 kg/m2 , median interval: 2.6 years), with lifestyle intervention (BMI: -3.4
      kg/m2 , interval: 1.2 years) and pharmacological therapy (BMI: -2.3 kg/m2 ,
      interval: 0.8 years) being less effective. Eighty percent of participants
      reporting follow-up weight remained in the obesity range. CONCLUSIONS: IRHOD
      identified a large cohort with self-reported HyOb. Surgical therapy was most
      effective at weight reduction. Nutritional counseling and pharmacotherapy
      modestly improved BMI. Stepwise treatment strategy for HyOb (including
      nutritional, pharmacological, and surgical therapies in an experienced center)
      may be most valuable.

PMID- 30296364
TI  - An asymmetrical dual coating on the stent prepared by ultrasonic atomization.
AB  - This study aims to design an asymmetric dual coating (ADC) on the stent by
      ultrasonic atomization to solve the problem of delayed endothelialization and
      late or very late stent thrombosis which caused by drug eluting stent (DES) with
      symmetric coating. Chitosan-loaded monoclonal platelet glycoprotein IIIa receptor
      antibody SZ-21 coating (CSC) was sprayed on inner surface of stents, and outer
      surface was sprayed CSC and poly(lactic-co-glycolic acid) (PLGA) loaded with
      docetaxel (DTX) coating (PDC). The coated surface was uniform without aggregation
      and no shedding phenomenon either before or after stent expanded. Fluorescence
      labeling has confirmed that the coating has an asymmetric structure. The
      cumulative release for SZ-21 and DTX was 40.11% and 27.22% within first 24 h,
      then DTX became the major released drug from 24 h to 7 d, after released for 28 d
      about 40% of the SZ-21 and 50% DTX still remained on the coated stent. It
      achieved that ADC can inhibit thrombosis at earlier period and inhibit vascular
      smooth muscle cells (VSMCs) proliferation at later period. And that ADC has good
      hemocompatibility and can significantly inhibit VSMCs proliferation. Finally, 4
      and 12 weeks after the stent with ADC implanted into rabbit carotid arteries, it
      showed that the stent with ADC was safe and could effectively prevent thrombosis
      and in-stent restenosis. (c) 2018 Wiley Periodicals, Inc. J. Biomed. Mater. Res.
      Part B, 2018.

PMID- 30296365
TI  - Large-Size Transparent Wood for Energy-Saving Building Applications.
AB  - As an energy-saving building material, transparent wood (TW) is highly attractive
      because of the advantages of high optical transmittance, excellent mechanical
      properties, and good thermal insulation. However, the current research is limited
      to fabricating small-size samples in the laboratory because thick or large-size
      transparent wood is almost impossible to be achieved. A method that can easily
      and efficiently produce transparent wood with any size and any thickness is
      desirable for practical applications. Transparent wood made from wood fibers as a
      substrate allows the cell walls to bind more tightly to the impregnated polymer,
      resulting in high light transmittance. Compared with wood prepared by using
      previously reported approaches, the transparent wood prepared by this new method
      not only retains the same advantages but also has higher preparation efficiency
      and is suitable for large-scale production. Under a simulated real environment,
      the retainability of indoor temperature by a sample house utilizing the
      transparent wood reveals excellent thermal insulation of the fiber-based
      transparent wood owing to its low thermal conductivity, showing significant
      benefits in saving thermal energy.

PMID- 30296366
TI  - Gut Microbiota and Body Weight in School-Aged Children: The KOALA Birth Cohort
      Study.
AB  - OBJECTIVE: This study aimed to examine the intestinal microbiota composition of
      school-aged children in association with (over)weight. METHODS: The fecal
      microbiota composition of 295 children was analyzed using the Human Intestinal
      Tract Chip. Anthropometric outcomes (overweight [BMI  >=  85th percentile], age-
      and sex-standardized BMI and weight z scores) were measured at 6 to 7 years of
      age, and elastic net was used to select genus-like bacterial groups related to
      all anthropometric outcomes. Subsequently, multiple linear and logistic
      regression models were used to model associations between selected bacterial
      groups and anthropometric measures while controlling for confounders. RESULTS:
      Prevotella melaninogenica, Prevotella oralis, Dialister, and uncultured
      Clostridiales II (UCII) accounted for 26.1% of the variation in microbiota
      composition. Several bacterial groups were inversely associated with the
      anthropometric outcomes: Sutterella wadsworthensis, Marvinbryantia formatexigens,
      Prevotella melanogenica, P oralis, Burkholderia, uncultured Clostridiales II, and
      Akkermansia, while Streptococcus bovis was positively associated with overweight.
      Microbial diversity and richness, and Bacteroidetes to Firmicutes ratio, were not
      significantly associated with any of the outcomes. CONCLUSIONS: In the largest
      population-based study on childhood gut microbiota and body weight so far, both
      new and previously identified bacterial groups were found to be associated with
      overweight. Further research should elucidate their role in energy metabolism.

PMID- 30296367
TI  - [ADHERENCE TO THE TREATMENT IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND WAYS TO
      ITS OPTIMIZATION].
AB  - A total of 148 patients (50 men and 98 women) with type 2 diabetes who were
      hospitalized in the endocrinology department "Nizhny Novgorod Regional Hospital
      N.A. Semashko". It was shown based on the Morisky-Green scale that 91 patients
      (61.4%) did not comply with the doctor's recommendation. 57 (38.6%) patients
      adhered to the treatment. The patients showing poor compliance with the treatment
      were divided randomly into two groups. One was comprised of patients with type 2
      diabetes (n = 45) who had been trained in the school of diabetic patients,
      provided with a special literature and kept a diary of self-monitoring blood
      glucose. The second group consisted of patients with type 2 diabetes (n = 46)
      also trained at the school of diabetes and provided with the relevant literature
      but were under active control (telephone calls, visits to the center). The year
      long prospective study demonstrated that adherence to treatment increased in the
      entire cohort. However, statistically significant positive dynamics of clinical
      and biochemical parameters was achieved only in the group of patients actively
      monitored by medical personnel.

PMID- 30296368
TI  - [VENOUS ECTASIA OF GASTRIC ANTRUM].
AB  - Gastric antral vascular ectasia (GAVE) is an uncommon but often severe cause of
      upper gastrointestinal bleeding. GAVE may be asymptomatic or accompanied by
      clinical anemia or overt gastrointestinal bleeding. The diagnosis is mainly based
      on pathognomonic endoscopic pattern, defined as "watermelon stomach", located in
      antrum. Autoimmune disorders aye co-existing in about 60% of patients with GAVE,
      chirrosis in about 30%, and cardiac or renal failure in 10%.The "golden
      standarden" treatment of GAVE is endoscopic argon plasma coagulation (APC). There
      is poor information about diagnostics and treatment of GAVE in the domestic
      literature. The analysis of the presented materials shows that correct
      diagnostics takes much time and the choice of the optimum optimal treatment
      strategy encounters difficulty. Our experience with diagnostics and therapy of
      GAVE is based on the treatment of 4 patients. The diagnosis of GAVE was
      established within the period from 5 months to 1.5 years after onset of the
      disease. In two cases, GAVE was asymptomatic. Two patients with severe anemia
      completed endoscopic treatment; in one case, APC was supplemented by laser
      coagulation and bipolar coagulation. The implementation of laser coagulation
      caused some technical difficulties. Treatment of both patients was successful.
      Endoscopy pivotal for diagnosis of GAVE is the main method of its treatment. Due
      to the large number of diagnostic errors and the importance of correct diagnosis
      of GAVE, it is necessary to pay attention to this issue in training programs for
      endoscopists.

PMID- 30296369
TI  - [RISK FACTORS OF DEATH IN DIABETES MELLITUS].
AB  - Objective: To study risk factors of death in diabetes mellitus (DM). Materials
      and methods: This prospective cohort study included 337 patients with compromised
      carbohydrate metabolism (36 with impaired fasting glycemia or impaired glucose
      tolerance, 80 with type 1 diabetes, 194 with type 2 diabetes, 27 with diabetes
      due to chronic pancreatitis). Mean follow-up was 11.2+/-4.8 years (from 1 January
      1995 through 31 December 2014). We investigated causes and risk factors of death
      in patients with impaired carbohydrate metabolism. Results: 115 patients died
      during the study period. The most common causes of death of patients with type 1
      and 2 diabetes are cardiovascular diseases and cancer. Risk factors of death in
      type 1 DM include cardiovascular disease, diabetic nephropathy and retinopathy.
      Patients die at a younger age due to early onset of the disease. In type 2
      diabetes risk factors of death are cardiovascular and oncologic diseases,
      nephropathy, the use of insulin. Patients die in elderly and senile age due to
      the late onset of diabetes. Gender differences in mortality associated with type
      1 and 2 diabetes mellitus were not observed. Conclusion: Main causes of death in
      patients with type 1 and 2 DM are cardiovascular diseases and cancer. Risk
      factors of death include macro - and microvascular complications.

PMID- 30296370
TI  - Novel Candy-like Cu4O3 Microstructure: Facile Wet Chemical Synthesis, Formation
      Mechanism, and Good Long-Term Antibacterial Activities.
AB  - The novel candy-like Cu4O3 microstructure has been synthesized successfully for
      the first time by a facile wet chemical method, and the formation mechanism was
      studied based on series of control experiments. The antibacterial activities of
      the candy-like Cu4O3 were evaluated by means of Gram-negative Escherichia coli (
      E. coli) and Gram-positive Staphylococcus saureus ( S. aureus). The antibacterial
      mechanism was investigated by tracing the morphology evolution of the bacteria.
      The results show that the candy-like Cu4O3 microstructure was formed underwent
      the route of Cu(NH3)42+ -> Cu(OH)42- -> Cu(OH)2 -> CuO -> Cu4O3 nuclei -> Cu4O3
      crystal growth -> candy-like Cu4O3, and optimal reaction conditions are required
      to obtain the candy-like Cu4O3. The candy-like Cu4O3 microstructure exhibits good
      long-term antibacterial activities to both E. coli and S. aureus bacteria.
      Critical concentration of Cu2+ ions released from the candy-like Cu4O3 was found
      responsible for the sudden increase beyond 90% in antibacterial activity.

PMID- 30296371
TI  - Syntheses of Molybdenum Oxo Benzylidene Complexes.
AB  - The reaction between Mo(O)(CHAro)(ORF6)2(PMe3) (Aro = ortho-methoxyphenyl, ORF6 =
      OCMe(CF3)2) and 2 equiv of LiOHMT (OHMT = O-2,6-(2,4,6-Me3C6H2)2C6H3) leads to
      Mo(O)(CHAro)(OHMT)2, an X-ray structure of which shows it to be a trigonal
      bipyramidal anti benzylidene complex in which the o-methoxy oxygen is coordinated
      to the metal trans to the apical oxo ligand. Addition of 1 equiv of water (in
      THF) to the benzylidyne complex, Mo(CArp)(OR)3(THF)2 (Arp = para-methoxyphenyl,
      OR = ORF6 or OC(CF3)3 (ORF9)) leads to formation of {Mo(CArp)(OR)2(MU
      OH)(THF)}2(MU-THF) complexes. Addition of 1 equiv of a phosphine (L) to
      Mo(CArp)(ORF9)3(THF)2 in THF, followed by addition of 1 equiv of water, all at
      room temperature, yields Mo(O)(CHArp)(ORF9)2(L) complexes in good yields for
      several phosphines (e.g., PMe2Ph (69% by NMR), PMePh2 (59%), PEt3 (69%), or P( i
      Pr)3 (65%)). The reaction between Mo(O)(CHArp)(ORF9)2(PEt3) and 2 equiv of LiOHMT
      proceeds smoothly at 90  degrees C in toluene to give Mo(O)(CHArp)(OHMT)2, a four
      coordinate syn alkylidene complex. Mo(O)(CHArp)(OHMT)2 reacts with ethylene (1
      atm in C6D6) to give (in solution) a mixture of Mo(O)(CHArp)(OHMT)2,
      Mo(O)(CH2)(OHMT)2, and an unsubstituted square pyramidal metallacyclobutane
      complex, Mo(O)(CH2CH2CH2)(OHMT)2, along with ethylene and ArpCH?CH2.
      Mo(O)(CHArp)(OHMT)2 also reacts with 2,3-dicarbomethoxynorbornadiene to yield syn
      and anti isomers of the "first-insertion" products that contain a cis C?C bond.

PMID- 30296372
TI  - Lanthanidocenes: Synthesis, Structure, and Bonding of Linear Sandwich Complexes
      of Lanthanides.
AB  - The Article presents the synthesis, structure, and bonding of a series of neutral
      and linear sandwich compounds with the cyclononatetraenyl (Cnt) ligand and
      divalent lanthanides. These compounds account for the emergence of the
      lanthanidocene series in reference to the ferrocene and uranocene. The synthetic
      strategy uses the solubility difference between two conformational isomers of the
      ligand, as well as the isomerization of the compounds induced by solvent
      coordination, yielding the isomorphous and isostructural neutral and rigorously
      linear sandwich complexes. The molecular structures feature a Cnt-Ln-Cnt angle of
      180 degrees  and a ring size close to the Cnt-Cnt(centroid) distance. A
      qualitative molecular orbital diagram is provided, in D9 d symmetry, and DFT
      calculations enforce the bonding model.

PMID- 30296373
TI  - Tunable Stability of Imidazotetrazines Leads to a Potent Compound for
      Glioblastoma.
AB  - Even in the era of personalized medicine and immunotherapy, temozolomide (TMZ), a
      small molecule DNA alkylating agent, remains the standard-of-care for
      glioblastoma (GBM). TMZ has an unusual mode-of-action, spontaneously converting
      to its active component via hydrolysis in vivo. While TMZ has been FDA approved
      for two decades, it provides little benefit to patients whose tumors express the
      resistance enzyme MGMT and gives rise to systemic toxicity through
      myelosuppression. TMZ was first synthesized in 1984, but certain key derivatives
      have been inaccessible due to the chemical sensitivity of TMZ, precluding broad
      exploration of the link between imidazotetrazine structure and biological
      activity. Here, we sought to discern the relationship between the hydrolytic
      stability and anticancer activity of imidazotetrazines, with the objectives of
      identifying optimal timing for prodrug activation and developing suitable
      compounds with enhanced efficacy via increased blood-brain barrier penetrance.
      This work necessitated the development of new synthetic methods to provide access
      to previously unexplored functionality (such as aliphatic, ketone, halogen, and
      aryl groups) at the C8 position of imidazotetrazines. Through synthesis and
      evaluation of a suite of compounds with a range of aqueous stabilities (from 0.5
      to 40 h), we derive a predictive model for imidazotetrazine hydrolytic stability
      based on the Hammett constant of the C8 substituent. Promising compounds were
      identified that possess activity against a panel of GBM cell lines, appropriate
      hydrolytic and metabolic stability, and brain-to-serum ratios dramatically
      elevated relative to TMZ, leading to lower hematological toxicity profiles and
      superior activity to TMZ in a mouse model of GBM. This work points a clear path
      forward for the development of novel and effective anticancer imidazotetrazines.

PMID- 30296374
TI  - Structural and Computational Assessment of the Influence of Wet-Chemical Post
      Processing of the Al-Substituted Cubic Li7La3Zr2O12.
AB  - Li7La3Zr2O12 (LLZO) and related compounds are considered as promising candidates
      for future all-solid-state Li-ion battery applications. Still, the processing of
      those materials into thin membranes with the right stoichiometry and crystal
      structure is difficult and laborious. The sensitivity of the Li-ion conductive
      garnets against moisture and the associated Li+/H+ cation exchange makes their
      processing even more difficult. Formulation of suitable polymer/ceramic hybrid
      solid state electrolytes could be a prosperous way to reach the future large
      scale production of solid state Li-ion batteries. In fact, solvent mediated
      and/or slurry based wet-processing of the LLZO, e.g., tape-casting, could result
      in irreversible Li-ion loss of the pristine material due to Li+/H+ cation
      exchange. The concomitant structural changes and loss in functionality in terms
      of Li-ion conductivity are the results of the above process. Therefore, in the
      present work a systematic study on the chemical stability and structural
      retention of Al-substituted LLZO in different solvents is reported. It was found
      that Li+/H+ exchange in LLZO occurs upon solvent immersion, and its magnitude is
      dependent on the availability of -OH functional groups of the solvent molecules.
      As a result, a larger degree of Li+/H+ exchange causes higher increase of the
      lattice parameter of the LLZO, determined by synchrotron diffraction analyses.
      The expansion of the cubic unit cell was ascertained, when Li+ was replaced by H+
      in the host lattice, by ab initio computational studies. The application of the
      most common solvent as dispersion medium, i.e., high purity water, causes the
      most significant Li+/H+ exchange and, therefore, structural change, while
      acetonitrile was proven to be the best suitable solvent for wet postprocessing of
      LLZO. Finally, computational calculations suggested that the Li+/H+ exchange
      could result in diminished ionic, i.e., mixed Li+-H+, conductivity due to the
      insertion of protons with lower mobility than that of Li-ions.

PMID- 30296375
TI  - Erlotinib-Guided Self-Assembled Trifunctional Click Nanotheranostics for
      Distinguishing Druggable Mutations and Synergistic Therapy of Nonsmall Cell Lung
      Cancer.
AB  - The outcome of molecular targeted therapies is restricted by the ambiguous
      molecular subtypes of nonsmall cell lung cancer (NSCLC), which are difficult to
      be defined with druggable mutations, and the inevitable emergence of drug
      resistance. Here we used the Cu-catalyzed click chemistry to synthesize a
      chitosan-based self-assembled nanotheranostics (CE7Ns) composed of a near
      infrared (NIR) fluorescent photosensitizer Cy7 and molecular targeted drug
      erlotinib. The well-characterized CE7Ns can release erlotinib and Cy7 fast under
      acidic condition in the presence of lysozyme, distinguish three molecular
      subtypes of NSCLC, and specifically bind to the erlotinib-sensitive epidermal
      growth factor receptor (EGFR)-mutated PC-9 cells. The uptake of CE7Ns is much
      more in PC-9 cells than in other NSCLC cells, thus generating a notable
      fluorescence signal in PC-9 cells. Upon NIR irradiation, Cy7 in CE7Ns produces
      high reactive oxygen species in PC-9 cells. The synergistic effect between
      erlotinib-targeted therapy and photodynamic therapy significantly up-regulates
      cancer suppressor p53 and inhibits Survivin, which results in more apoptosis and
      cell cycle arrest. Upon intravenous administration, the erlotinib-guided CE7Ns
      significantly accumulate in PC-9-seeded mouse lungs and produce strong
      fluorescence. Upon NIR irradiation, CE7Ns significantly inhibit the
      subcutaneously implanted PC-9 tumor growth. This study provides, for the first
      time, a novel strategy to synthesize a multifunctional theranostic entity to
      simultaneously distinguish and image druggable mutations and combine targeted
      therapy with photodynamic therapy to overcome drug resistance.

PMID- 30296376
TI  - Evaluation of Novel Tumor-Targeted Near-Infrared Probe for Fluorescence-Guided
      Surgery of Cancer.
AB  - Because the most reliable therapy for cancer involves quantitative resection of
      all diseased tissue, considerable effort has been devoted to improving a
      surgeon's ability to locate and remove all malignant lesions. With the aid of
      improved optical imaging equipment, we and others have focused on developing
      tumor-targeted fluorescent dyes to selectively illuminate cancer nodules during
      surgery. We describe here the design, synthesis, optical properties, in vitro and
      in vivo tumor specificity/affinity, pharmacokinetics, preclinical toxicology, and
      some clinical application of a folate receptor (FR)-targeted NIR dye (OTL38) that
      concentrates specifically in cancer tissues and clears rapidly from healthy
      tissues. We demonstrate that OTL38 binds FR-expressing cells with ~1 nM affinity
      and eliminates from receptor negative tissues with a half-time of <30 min. We
      further show that OTL38 enables visualization of malignant lesions at
      concentrations less than 100-fold those required to elicit signs of toxicity.
      Since OTL38 also provides excellent tumor contrast in both murine tumor models
      and human cancer patients, we conclude that OTL38 constitutes an excellent NIR
      dye for fluorescence-guided resection of malignant lesions in cancer patients.

PMID- 30296377
TI  - Engineered Fusion Proteins for Efficient Protein Secretion and Purification of a
      Human Growth Factor from the Green Microalga Chlamydomonas reinhardtii.
AB  - Light-driven recombinant protein (RP) production in eukaryotic microalgae offers
      a sustainable alternative to other established cell-culture systems. RP
      production via secretion into the culture medium enables simple product
      separation from the cells adding a layer of process value in addition to the
      algal biomass, which can be separately harvested. For the model microalga
      Chlamydomonas reinhardtii, a broad range of molecular tools have been established
      to enable heterologous gene expression; however, low RP production levels and
      unreliable purification from secretion concepts have been reported. Domesticated
      C. reinhardtii strains used for genetic engineering are often cell-wall
      deficient. These strains nevertheless secrete cell-wall components such as
      insoluble (hydroxy)proline-rich glycoproteins into the culture media, which
      hinder downstream purification processes. Here, we attempted to overcome
      limitations in secretion titers and improve protein purification by combining
      fusion partners that enhance RP secretion and enable alternative aqueous two
      phase (ATPS) RP extraction from the culture medium. Protein fusions were
      strategically designed to contain a stably folded peptide, which enhanced
      secretion capacities and gave insights into (some) regulatory mechanisms
      responsible for this process in the algal host. The elevated protein titers
      mediated by this fusion were then successfully applied in combination with a
      fungal hydrophobin tag, which enabled protein purification from the complex
      microalgal extracellular environment by ATPS, to yield functional recombinant
      human epidermal growth factor (hEGF) from the algal host.

PMID- 30296379
TI  - NiO/NiCo2O4 Truncated Nanocages with PdO Catalyst Functionalization as Sensing
      Layers for Acetone Detection.
AB  - Achieving a novel structural construction and adopting appropriate catalyst
      materials are key to overcoming inherent limitations of gas sensors in terms of
      designing sensing layers. This work introduces NiO/NiCo2O4 truncated nanocages
      functionalized with PdO nanoparticles, which were proved to possess the ability
      of effective acetone detection. The device realized an enhanced acetone-sensing
      sensitivity, together with excellent selectivity and long-term stability. The
      sensing performance is far better than sensors based on NiO/NiCo2O4 solid
      nanocubes and NiO/NiCo2O4 truncated nanocages without PdO decorating, which is
      related to cooperative effects of the high specific surface area and efficient
      catalytic activity. The results provide promising metal-organic frameworks (MOFs)
      derived material with the optimization of catalytic performance, demonstrating
      the remarkable potential for acetone sensors.

PMID- 30296378
TI  - Dual-Ion-Mode MALDI MS Detection of Small Molecules with the O-P,N-Doped
      Carbon/Graphene Matrix.
AB  - It is challenging to realize a dual-ion mode of matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for
      detecting small molecules. Herein, graphene coated by porous amorphous carbon
      with P-O surface group and codoped by phosphorus and nitrogen (O-P,N-C/G) was
      synthesized from an aerogel formed by phytic acid, polyaniline, and
      electrochemically exfoliated graphene. The carbon material synthesized has the
      feature of large surface area (583 m2/g), good electrical conductivity, strong UV
      absorption, heteroatom doping, and surface functional groups suitable for laser-
      induced desorption/ionization. It was employed as a novel matrix suitable for
      both positive-ion and negative-ion modes in MALDI-TOF MS for the analysis of
      various small molecules including amino acids, small peptides, saccharides,
      drugs, and environmental pollutants, significantly outperforming control
      materials and a traditional CHCA (alpha-cyano-4-hydroxycinnamic acid) or 2,5
      dihydroxybenzoic (DHB) matrix. Remarkably, the detection limit of the anticancer
      drugs (5-fluorouracil and ellagic acid) reaches 50 pmol. In addition, nice MALDI
      TOF MS images can be mapped to detect mixed amino acids corresponding to
      homogeneous distribution of ion intensity. The monosaccharides and disaccharides
      can be distinguished by using the new matrix. Last but not least, it can be used
      to quantitatively detect glucose in human serum and soft drinks
      (glucose/fructose, 203.1 mM) without adding standards.

PMID- 30296380
TI  - Morphological Engineering of Winged Au@MoS2 Heterostructures for Electrocatalytic
      Hydrogen Evolution.
AB  - Molybdenum disulfide (MoS2) has been recognized as a promising cost-effective
      catalyst for water-splitting hydrogen production. However, the desired
      performance of MoS2 is often limited by insufficient edge-terminated active
      sites, poor electrical conductivity, and inefficient contact to the supporting
      substrate. To address these limitations, we developed a unique nanoarchitecture
      (namely, winged Au@MoS2 heterostructures enabled by our discovery of the "seeding
      effect" of Au nanoparticles for the chemical vapor deposition synthesis of
      vertically aligned few-layer MoS2 wings). The winged Au@MoS2 heterostructures
      provide an abundance of edge-terminated active sites and are found to exhibit
      dramatically improved electrocatalytic activity for the hydrogen evolution
      reaction. Theoretical simulations conducted for this unique heterostructure
      reveal that the hydrogen evolution is dominated by the proton adsorption step,
      which can be significantly promoted by introducing sufficient edge active sites.
      Our study introduces a new morphological engineering strategy to make the
      pristine MoS2 layered structures highly competitive earth-abundant catalysts for
      efficient hydrogen production.

PMID- 30296381
TI  - In Vivo and Cellular Trafficking of Acetalated Dextran Microparticles for
      Delivery of a Host-Directed Therapy for Salmonella enterica Serovar Typhi
      Infection.
AB  - Previously we have encapsulated host-directed therapy AR-12 into acetalated
      dextran (Ace-DEX) microparticles (MPs) to mitigate drug toxicity and passively
      target phagocytic host cells. Herein, we have improved upon our initial emulsion
      based formulation of Ace-DEX MPs encapsulating AR-12 (AR-12/MPs) by improving the
      drug encapsulation efficiency, evaluating sterilization processes for
      manufacturing, and understanding cellular and in vivo trafficking of the MPs. By
      using an alternative solvent system, ethyl acetate, we report an increased
      encapsulation efficiency of AR-12 while maintaining the pH-responsive degradation
      kinetics of Ace-DEX MPs. To better manufacture this novel antimicrobial
      formulation, we sterilized AR-12/MPs by gamma irradiation or ethylene oxide and
      evaluated their efficacy against intracellular Salmonella enterica serovar Typhi.
      Sterilized AR-12/MPs resulted in a significant reduction in intracellular
      bacterial burden compared to Blank/MPs. We also characterized intracellular
      trafficking of Ace-DEX MPs encapsulating fluorophores, which demonstrated
      internalization of MPs in endo/lysosomal compartments and time and degradation
      rate dependent lysosomal escape into cytosolic compartments. Additionally, in
      vivo toxicity was mitigated following encapsulation of AR-12, where the maximum
      tolerated dose of AR-12 was increased compared to soluble treatment via
      intranasal, intravenous, and intraperitoneal administration routes. Following in
      vivo trafficking of Ace-DEX MPs via the same routes, intranasal administration
      demonstrated the highest accumulation in the lungs, liver, and kidneys, which
      persisted out to 240 h. Overall, we have advanced the formulation of this host
      directed therapy and broadened the understanding of Ace-DEX MP delivery.

PMID- 30296382
TI  - Candida rugosa lipase encapsulated with magnetic sporopollenin: design and
      enantioselective hydrolysis of racemic arylpropanoic acid esters.
AB  - The aim of this study was to prepare the encapsulation of Candida rugosa lipase
      (CRL) with magnetic sporopollenin. The sporopollenin was covalent immobilized
      onto magnetic nanoparticles (Fe3O4), grafted amino (APTES), or epoxy groups
      (EPPTMS). CRL was sol-gel encapsulated in the presence of magnetic
      sporopollenin/Fe3O4 nanoparticles. The influence of activation agents ([3-(2,3
      epoxypropoxy) propyl] trimethoxysilane (EPPTMS), (3-Aminopropyl)triethoxysilane
      (APTES) and pH and thermal stabilities of the biocatalyst were assessed.
      Experimental data showed the improved catalytic activity at different pH and
      temperature values. At 60  degrees C, free lipase lost its initial activity
      within 80 min of time, although the encapsulated lipases retained their initial
      activities of about 65% by APTES and 60% by EPPTMS after 120 min of heat
      treatment at 60  degrees C. The catalytic properties of the encapsulated lipases
      were utilized to hydrolysis of racemic aromatic carboxylic acid methyl esters
      (Naproxen and 2-phenoxypropionic acid). The results show that the sporopollenin
      based encapsulated lipase (Fe-A-Spo-E) has greater enantioselectivity and
      conversion in comparison with the encapsulated lipase without supports (lipase
      enc).

PMID- 30296383
TI  - Subjective discomfort caused by vertical whole-body vibration in the frequency
      range 2-100 Hz.
AB  - Current standards assume the same frequency weightings for discomfort at all
      magnitudes of vibration, whereas biodynamic and psychological studies show that
      the frequency-dependence of objective and subjective responses of the human body
      depends on the magnitude of vibration. This study investigated the discomfort of
      seated human body caused by vertical whole-body vibration over the frequency
      range 2-100 Hz at relatively high magnitudes from 1.0 to 2.5 ms-2 r.m.s. Twenty
      eight subjects (15 males and 13 females) judged the discomfort using the absolute
      magnitude estimation method. The rate of growth of discomfort with increasing
      vibration magnitude was highly depended on the frequency, so the shapes of the
      equivalent comfort contours depended on the magnitude of vibration and no single
      frequency weighting would be appropriate for all magnitudes. The equivalent
      comfort contours indicated that the standards and previous relevant studies
      underestimated the vibration discomfort at frequencies greater than about 30 Hz.
      Practitioner summary: The discomfort caused by vertical vibration at relatively
      high frequencies can be severe, particularly at relatively great magnitudes in
      transport. This study provides the frequency-dependence of vibration discomfort
      at 2-100 Hz, and shows how the frequency weightings in the current standards can
      be improved at relatively high frequencies.

PMID- 30296384
TI  - Cognitive impairment in chronic obstructive pulmonary disease: disease burden,
      determinants and possible future interventions.
AB  - INTRODUCTION: Cognitive impairment (CI) is an important but an under-recognized
      extra-pulmonary feature of chronic obstructive pulmonary disease (COPD). It is
      related to the burden of disability, worse health outcomes, and impaired self
      management. Areas covered: CI includes deterioration of a wide range of cognitive
      functions, such as memory and various executive functions. Risk of
      hospitalization might be higher in patients with COPD compared to those without,
      with CI negatively impacting the wellbeing of patients with COPD. Disease
      specific factors such as hypoxemia and inflammation, lifestyle factors such as
      dietary insufficiencies and lack of physical activity, and comorbidities such as
      obstructive sleep apnea and depression are likely to synergistically contribute
      to the development of CI in COPD. Tailored interventions can possibly improve CI
      in COPD, but this needs further investigation. Expert commentary: Further
      research is warranted involving the optimization of neuropsychological testing
      for screening and outcome assessment, longitudinal studies to investigate the
      development of CI in COPD over time, and randomized clinical trials to test the
      feasibility and efficacy of promising interventions.

PMID- 30296385
TI  - Improved accumulation of betulin and betulinic acid in cell suspension culture of
      Betula pendula roth by abiotic and biotic elicitors.
AB  - Betulin (B) and betulinic acid (BA) are two triterpenes with diverse
      pharmacological and physiological actions. Elicitation of Betula pendula Roth
      cell cultures by elicitors is an excellent strategy to increase B and BA levels.
      Six abiotic and biotic elicitors were studied to improve accumulation of B and BA
      in the cell culture of B. pendula. The B and BA production in treated cells was
      verified by HPLC. The results showed the maximum growth index (7) on day 3 in
      cells treated with 0.5 mg L-1 chlorocholine chloride (CCC). The increased
      accumulation of BA in the cells treated with 200 mg L-1 of chitosan was found to
      be 5.9 * (6.5 mg g-1 DW) higher over control cells. Treating the cells with 2 mg
      L-1 of CCC, after 7 days, led to 149.3* enhancement of B content (19.4 mg g-1 DW)
      over the controls. Production of this triterpenoid at a much shorter time with a
      much higher growth rate can be economic and lead to producing large amounts of B
      and BA for anti-cancer and HIV drugs preparation.

PMID- 30296386
TI  - Projected changes in particulate matter concentrations in the South Coast Air
      Basin due to basin-wide reductions in nitrogen oxides, volatile organic compounds
      and ammonia emissions.

PMID- 30296388
TI  - Suspected capture myopathy in an alpaca (Vicugna pacos) following a dog attack.

PMID- 30296387
TI  - Betrixaban for first-line venous thromboembolism prevention in acute medically
      ill patients with risk factors for venous thromboembolism.
AB  - INTRODUCTION: Compared to other direct oral anticoagulants, betrixaban has a
      longer half-life, smaller peak-trough variance, minimal renal clearance, and
      minimal hepatic Cytochrome P (CYP) metabolism. The Acute Medically Ill VTE
      Prevention with Extended Duration Betrixaban (APEX) trial evaluated the efficacy
      and safety of extended duration betrixaban compared to standard duration
      enoxaparin in acutely ill hospitalized patients. Areas covered: This article
      describes the role of betrixaban in the prevention of venous thromboembolism
      (VTE) in acutely ill medical patients. This article provides a consolidated
      summary of the primary APEX study findings as well as prespecified and
      exploratory substudies. This article also provides a review of the results of
      studies in which other direct factor Xa inhibitors have been evaluated in an
      extended duration regimen in this patient population. Expert commentary: While
      previous agents have demonstrated that extended duration VTE prophylaxis can be
      efficacious, betrixaban is the first agent to demonstrate efficacy without an
      increase in major bleeding. The totality of the data from the APEX trial supports
      extended duration betrixaban for VTE prophylaxis in the acute medically ill
      patient population. As such, betrixaban has been approved in the USA for extended
      VTE prophylaxis in at-risk acute medically ill patients.

PMID- 30296389
TI  - The relationship between atmospheric pollutant emissions and fuel qualities of
      Inland Vessels in Jiangsu Province, China.

PMID- 30296390
TI  - Mucins and Their Role in Shaping the Functions of Mucus Barriers.
AB  - We review what is currently understood about how the structure of the primary
      solid component of mucus, the glycoprotein mucin, gives rise to the mechanical
      and biochemical properties of mucus that are required for it to perform its
      diverse physiological roles. Macroscale processes such as lubrication require
      mucus of a certain stiffness and spinnability, which are set by structural
      features of the mucin network, including the identity and density of cross-links
      and the degree of glycosylation. At the microscale, these same features affect
      the mechanical environment experienced by small particles and play a crucial role
      in establishing an interaction-based filter. Finally, mucin glycans are critical
      for regulating microbial interactions, serving as receptor binding sites for
      adhesion, as nutrient sources, and as environmental signals. We conclude by
      discussing how these structural principles can be used in the design of synthetic
      mucin-mimetic materials and provide suggestions for directions of future work in
      this field.

PMID- 30296391
TI  - Caveolae: Structure, Function, and Relationship to Disease.
AB  - The plasma membrane of eukaryotic cells is not a simple sheet of lipids and
      proteins but is differentiated into subdomains with crucial functions. Caveolae,
      small pits in the plasma membrane, are the most abundant surface subdomains of
      many mammalian cells. The cellular functions of caveolae have long remained
      obscure, but a new molecular understanding of caveola formation has led to
      insights into their workings. Caveolae are formed by the coordinated action of a
      number of lipid-interacting proteins to produce a microdomain with a specific
      structure and lipid composition. Caveolae can bud from the plasma membrane to
      form an endocytic vesicle or can flatten into the membrane to help cells
      withstand mechanical stress. The role of caveolae as mechanoprotective and signal
      transduction elements is reviewed in the context of disease conditions associated
      with caveola dysfunction.

PMID- 30296392
TI  - Writing, Reading, and Translating the Clustered Protocadherin Cell Surface
      Recognition Code for Neural Circuit Assembly.
AB  - The ability of neurites of individual neurons to distinguish between themselves
      and neurites from other neurons and to avoid self (self-avoidance) plays a key
      role in neural circuit assembly in both invertebrates and vertebrates. Similarly,
      when individual neurons of the same type project into receptive fields of the
      brain, they must avoid each other to maximize target coverage (tiling).
      Counterintuitively, these processes are driven by highly specific homophilic
      interactions between cell surface proteins that lead to neurite repulsion rather
      than adhesion. Among these proteins in vertebrates are the clustered
      protocadherins (Pcdhs), and key to their function is the generation of enormous
      cell surface structural diversity. Here we review recent advances in
      understanding how a Pcdh cell surface code is generated by stochastic promoter
      choice; how this code is amplified and read by homophilic interactions between
      Pcdh complexes at the surface of neurons; and, finally, how the Pcdh code is
      translated to cellular function, which mediates self-avoidance and tiling and
      thus plays a central role in the development of complex neural circuits. Not
      surprisingly, Pcdh mutations that diminish homophilic interactions lead to wiring
      defects and abnormal behavior in mice, and sequence variants in the Pcdh gene
      cluster are associated with autism spectrum disorders in family-based genetic
      studies in humans.

PMID- 30296393
TI  - Introduction: Challenges for Science: A Retrospective.

PMID- 30296394
TI  - Biomarkers of exposure and effect in a working population exposed to lead,
      manganese and arsenic.
AB  - Lead (Pb), manganese (Mn) and arsenic (As) are among the major toxicants in
      mining environments. Miners are commonly and repeatedly exposed to this toxic
      mixture. Some adverse effects may appear at concentrations below environmental
      quality guidelines for individual mixture components. Further, Pb, Mn, and As
      induce common adverse outcomes, such as interferences in the cholinergic system
      and heme synthesis. It is thus vital to monitor miners through biomarkers (BM),
      such that subclinical effects may be identified at an early stage. The main
      objectives of this study were to evaluate the exposure of a mining population to
      these three metals and determine alterations in cholinergic and heme synthesis
      parameters. Blood and urine samples of workers (n = 60) were obtained from a
      Portuguese mining industry and compared with a control population (n = 80). The
      levels of the metals were determined in biological samples, as well as urinary
      heme precursor levels, delta aminolevulinic acid (ALA) and porphyrins, and blood
      acetylcholinesterase (AChE) activity. The miners exhibited significantly higher
      values of Pb and As in blood and urine compared to control. In the case of Mn
      near or slightly higher than limit values were found. Our data show that heme
      precursors may be used simultaneously with metal levels as BMs for multiple metal
      exposures on an individual basis, resulting in 94.3% and 95.7% accuracy,
      respectively, in blood and urine, for subjects correctly identified with respect
      to occupation. This study also revealed that biological monitoring of this
      working population regarding metal body burden and heme precursor accumulation is
      advisable.

PMID- 30296395
TI  - Hepatitis B contact tracing: what works?
AB  - In 2012, over 239000 people were living in Australia with chronic hepatitis B
      (CHB). Australia's Second National Hepatitis B Strategy (2014) recommends testing
      contacts to increase identification of people with CHB, but it is generally
      poorly performed. CHB prevalence in Australia is increasing and contact tracing
      (CT) remains an untapped strategy for identifying infected individuals. A
      systematic CT system has been established in a government-funded primary health
      centre in Melbourne, which services 2000 refugees. This mixed-methods study aimed
      to describe the structure of the CT system, determine its effectiveness and
      identify enablers of success. The CT system's structure was elicited from field
      notes. CT effectiveness (proportion of contacts traced and serologically
      confirmed as infected or immune to HBV) was determined by auditing clinical
      records. Semi-structured interviews with seven health professionals were
      thematically analysed to identify enablers of CT success. Overall, 122 CHB index
      cases had 420 contacts. And 90.0% (n=380) of 420 contacts were successfully
      traced, 68.0% (n=83) of index cases had 100% of their contacts successfully
      traced and 80.7% (n=339) of all contacts were immune; 28.8% (n=121) had evidence
      of previous exposure and 55.0% (n=231) had evidence of vaccination. Also, 8.1%
      (n=34) were chronically infected. Interviews elicited seven themes important to
      the success of the CT system: Teamwork; Organisation; Health professional
      expertise; Patient education; Centralisation of the system; Influence of patient
      culture; and Use of nurses in CT. Teamwork and Organisation were previously
      unidentified in the literature. This CT system is successful and could be
      implemented elsewhere, provided an organised, cohesive, nurse-led team is
      established.

PMID- 30296397
TI  - Universal Screening for Social Needs in a Primary Care Clinic: A Quality
      Improvement Approach Using the Your Current Life Situation Survey.
AB  - CONTEXT: Kaiser Permanente's Care Management Institute created a screening tool,
      Your Current Life Situation (YCLS), which primarily is used to identify social
      needs for populations at risk of high health care utilization. OBJECTIVE: This
      frontline improvement project was designed to address key stakeholder concerns
      about implementing universal screening for social needs using the YCLS in a
      primary care clinic. METHODS: I conducted a rapid stakeholder analysis through
      informal conversations to identify the most important concerns. Four Plan-Do
      Study-Act cycles were conducted to answer stakeholder questions and address
      concerns. RESULTS: Stakeholders expressed concerns including YCLS length and low
      screening acceptability and the possibility that too few or too many patients may
      have social needs. Throughout the project's duration, 125 office visits occurred
      and 111 patients were screened. Among the patients for whom findings were
      positive, 27% requested help. Of the 14 patients who were not screened, only 1
      patient opted out of screening. Practitioners and medical assistants stated that
      administration of the YCLS screening tool did not disrupt clinic workflow.
      CONCLUSION: By using a frontline improvement approach, these investigators could
      answer questions and address concerns most important to local operational
      stakeholders when implementing screening for social needs. When practitioners
      conduct universal social needs screening and more fully understand social needs
      prevalence in a primary care clinic, resources can be tailored more effectively
      to accommodate patient needs.

PMID- 30296396
TI  - Relationship Between Adverse Childhood Experience Survey Items and Psychiatric
      Disorders.
AB  - CONTEXT: Developmental psychopathology theory suggests a relationship between
      early childhood adversity and mental disorder. OBJECTIVE: To examine the
      relationship between the specific items on the Adverse Childhood Experiences
      (ACE) survey and the International Classification of Diseases, Tenth Revision
      (ICD-10) categories of psychiatric diagnoses in a pediatric sample. DESIGN: The
      sample included patients enrolled in the Child and Adolescent Addiction Mental
      Health and Psychiatry Program with both a completed ACE survey and at least 1
      diagnosis of record (per admission). These criteria yielded 2 samples for each
      sex (ACE survey item frequencies and values in collapsed and multiple-admission
      groups). Data were analyzed employing tetrachoric correlation, hierarchical
      regression, and polychoric factor analysis. RESULTS: Hierarchical regression
      analysis identified that ICD-10 diagnostic categories, except for substance
      disorders, were not consistently related to ACE total score and tended to reduce
      the magnitude of the ACE total score in the multiple-admission group. Tetrachoric
      correlation revealed very low (< 0.4) positive and negative correlations between
      ICD-10 categories and ACE items in both multiple-admission and collapsed sample
      groups. Polychoric factor analysis indicated that the ACE survey items and the
      ICD-10 categories for both sexes were independent, with only the diagnostic ICD
      10 category substance disorders being marginally associated with the ACE items
      factor for females. CONCLUSION: The nominal relationship between ACE items and
      ICD-10 diagnostic categories indicates the need to include ACE assessment in
      advance of differential diagnosis and implementation of conventional mental
      health interventions for children and adolescents.

PMID- 30296398
TI  - Using Neighborhood-Level Census Data to Predict Diabetes Progression in Patients
      with Laboratory-Defined Prediabetes.
AB  - CONTEXT: Research on predictors of clinical outcomes usually focuses on the
      impact of individual patient factors, despite known relationships between
      neighborhood environment and health. OBJECTIVE: To determine whether US census
      information on where a patient resides is associated with diabetes development
      among patients with prediabetes. DESIGN: Retrospective cohort study of all
      157,752 patients aged 18 years or older from Kaiser Permanente Northern
      California with laboratory-defined prediabetes (fasting plasma glucose, 100 mg/dL
      125 mg/dL, and/or glycated hemoglobin, 5.7%-6.4%). We assessed whether census
      data on education, income, and percentage of households receiving benefits
      through the US Department of Agriculture's Supplemental Nutrition Assistance
      Program (SNAP) was associated with diabetes development using logistic regression
      controlling for age, sex, race/ethnicity, blood glucose levels, and body mass
      index. MAIN OUTCOME MEASURE: Progression to diabetes within 36 months. RESULTS:
      Patients were more likely to progress to diabetes if they lived in an area where
      less than 16% of adults had obtained a bachelor's degree or higher (odds ratio
      [OR] =1.22, 95% confidence interval [CI] = 1.09-1.36), where median annual income
      was below $79,999 (OR = 1.16 95% CI = 1.03-1.31), or where SNAP benefits were
      received by 10% or more of households (OR = 1.24, 95% CI = 1.1-1.4). CONCLUSION:
      Area-level socioeconomic and food assistance data predict the development of
      diabetes, even after adjusting for traditional individual demographic and
      clinical factors. Clinical interventions should take these factors into account,
      and health care systems should consider addressing social needs and community
      resources as a path to improving health outcomes.

PMID- 30296399
TI  - Inadequate Clinical Indications in Computed Tomography Chest and Abdomen/Pelvis
      Scans.
AB  - CONTEXT: As the use of computed tomography (CT) scans, which are expensive and
      result in considerable radiation exposure to the patient, continues to increase,
      communication between physicians and radiologists remains vital to explain the
      clinical context for the examination. However, the clinical information provided
      to the radiologist is often lacking. OBJECTIVE: To determine whether the clinical
      information provided in CT scan requests meets minimum criteria for requesting
      the examination. METHODS: We reviewed the clinical indications for 400 CT chest
      scans and 400 CT abdomen/pelvis scans performed from January 1, 2016, through
      March 8, 2016. We determined whether each CT study indication was complete on the
      basis of whether the clinical information included an adequate clinical history
      with 1) a primary symptom, 2) the location of the symptom, and 3) the duration of
      the symptom as well as a suspected etiology. RESULTS: Of the CT chest
      indications, 56 (14.0%) of the clinical histories were considered complete and 17
      (4.3%) had none of the components. A principal etiology was included in 195
      (48.8%) of the indications. Of the CT abdomen/pelvis indications, 94 (23.5%) of
      the clinical histories were complete and 13 (3.3%) had none of the components. A
      principal etiology was included in 173 (43.3%) of the indications. Only 23 (5.8%)
      of the CT chest studies and 35 (8.8%) of the CT abdomen/pelvis studies had
      information considered sufficient for the radiologist. CONCLUSION: The percentage
      of complete clinical indications for both CT chest and abdomen/pelvis scans was
      much lower than 50%, suggesting that more emphasis should be placed on providing
      complete clinical indications.

PMID- 30296400
TI  - Lessons Learned from Implementation of the Food Insecurity Screening and Referral
      Program at Kaiser Permanente Colorado.
AB  - Traditionally, health care systems have addressed gaps in patients' diet quality
      with programs that provide dietary counseling and education, without addressing
      food security. However, health care systems increasingly recognize the need to
      address food security to effectively support population health and the prevention
      and management of diet-sensitive chronic illnesses. Numerous health care systems
      have implemented screening programs to identify food insecurity in their patients
      and to refer them to community food resources to support food security. This
      article describes barriers encountered and lessons learned from implementation
      and expansion of the Kaiser Permanente Colorado's clinical food insecurity
      screening and referral program, which operates in collaboration with a statewide
      organization (Hunger Free Colorado) to manage clinic-to-community referrals. The
      immediate goals of clinical screening interventions described in this article are
      to identify households experiencing food insecurity, to connect them to
      sustainable (federal) and emergency (community-based) food resources, to
      alleviate food insecurity, and to improve dietary quality. Additional goals are
      to improve health outcomes, to decrease health care utilization, to improve
      patient satisfaction, and to better engage patients in their care.

PMID- 30296401
TI  - TET2: Is a potential gatekeeper for the action of thiazolidinedione in fat cells?

PMID- 30296402
TI  - High-intensity interval exercise impairs neuroelectric indices of reinforcement
      learning.
AB  - A single bout of high-intensity interval exercise (HIIE) improves behavioural
      measures of cognitive function; however, investigations using event-related
      potentials (ERPs) to examine the systems that underlie these cognitive
      improvements are lacking. The reward positivity is a positive-going ERP component
      that indexes reward processing evoked by 'win' feedback and is a candidate marker
      of an underlying human reinforcement learning system. While HIIE improves
      behavioural measures of learning, it is unknown how HIIE affects the amplitude of
      the reward positivity. Therefore, the purpose of this study was to investigate
      how HIIE affects reward positivity amplitude in response to reward feedback in
      university students. Using a single-group randomly assigned counterbalance
      crossover design, 25 healthy university students performed HIIE and control
      visits on separate days. Electroencephalographic data was recorded before (pre
      intervention) and 10 min after (post-intervention) the intervention period while
      participants played a novel gambling task. The HIIE intervention consisted of 4
      separate body-weight exercises totaling 11 min in duration, including rest. The
      control visit intervention consisted of quietly watching a nature documentary for
      11 min. Heart rate (HR) was measured at the same time intervals in both trials.
      Analysis revealed that HIIE significantly diminished the amplitude of the reward
      positivity whereas it remained unaffected in the control condition. HR was
      significantly higher following HIIE compared to control during post-intervention
      testing. These findings suggest that mechanisms of reinforcement learning are
      impaired shortly after HIIE cessation, possibly due to persistent, suboptimal
      arousal as evidenced by elevated HR post-HIIE.

PMID- 30296403
TI  - Social isolation impairs active avoidance performance and decreases neurogenesis
      in the dorsomedial telencephalon of rainbow trout.
AB  - Alterations in the social environment, such as isolating an individual that would
      normally live in a social group, can generate physiological responses that
      compromise an individual's capacity to learn. To investigate this, we tested
      whether social isolation impairs learning skills in the rainbow trout. We show
      that rainbow trout can achieve an active avoidance (AA) learning program with
      inter-individual variability. Moreover, c-Fos expression in dorsomedial
      telencephalon (Dm) correlates with the AA performance, indicating that this
      structure is involved in this cognitive task. Given that Dm participates in AA
      learning and this region is under plastic remodelling by addition of new-born
      neurons, we tested whether social isolation impinges on adult neurogenesis and,
      consequently, on the Dm cognitive outcome. Trout were reared for four weeks in
      control or isolated conditions. We found that social isolation diminished the
      percentage of adult-born neurons that are being incorporated into Dm network.
      Interestingly, the same isolation treatment also induced a severe deficit in the
      AA performance. Our results demonstrate a structure-to-function relationship
      between the Dm and the learning ability in an AA task, indicate that social
      isolation reduces the incorporation of adult-born neurons into Dm, and show that
      social isolation impairs the Dm-related cognitive function.

PMID- 30296404
TI  - Randomized trial of polychromatic blue-enriched light for circadian phase
      shifting, melatonin suppression, and alerting responses.
AB  - Wavelength comparisons have indicated that circadian phase-shifting and
      enhancement of subjective and EEG-correlates of alertness have a higher
      sensitivity to short wavelength visible light. The aim of the current study was
      to test whether polychromatic light enriched in the blue portion of the spectrum
      (17,000 K) has increased efficacy for melatonin suppression, circadian phase
      shifting, and alertness as compared to an equal photon density exposure to a
      standard white polychromatic light (4000 K). Twenty healthy participants were
      studied in a time-free environment for 7 days. The protocol included two baseline
      days followed by a 26-h constant routine (CR1) to assess initial circadian phase.
      Following CR1, participants were exposed to a full-field fluorescent light (1 *
      1014 photons/cm2/s, 4000 K or 17,000 K, n = 10/condition) for 6.5 h during the
      biological night. Following an 8 h recovery sleep, a second 30-h CR was
      performed. Melatonin suppression was assessed from the difference during the
      light exposure and the corresponding clock time 24 h earlier during CR1. Phase
      shifts were calculated from the clock time difference in dim light melatonin
      onset time (DLMO) between CR1 and CR2. Blue-enriched light caused significantly
      greater suppression of melatonin than standard light ((mean +/- SD) 70.9 +/-
      19.6% and 42.8 +/- 29.1%, respectively, p < 0.05). There was no significant
      difference in the magnitude of phase delay shifts. Blue-enriched light
      significantly improved subjective alertness (p < 0.05) but no differences were
      found for objective alertness. These data contribute to the optimization of the
      short wavelength-enriched spectra and intensities needed for circadian,
      neuroendocrine and neurobehavioral regulation.

PMID- 30296405
TI  - Barriers to Help-Seeking Behavior Among Women With Postpartum Depression.
AB  - Postpartum depression affects approximately 900,000 women annually, but only
      approximately 6% of these women seek psychological help (Postpartum, Progress,
      2016). This lack of help-seeking behavior must be addressed to decrease the
      negative effects of postpartum depression on maternal and infant outcomes. The
      purpose of this article is to describe the barriers that prevent women from
      seeking psychological help and provide suggestions to address these barriers.

PMID- 30296406
TI  - Aspirin to Prevent Sudden Cardiac Death in Athletes with High Coronary Artery
      Calcium Scores.
AB  - While proficient cardiac resuscitation has improved survival following cardiac
      arrest during road races in Japan, this accomplishment does not address coronary
      artery disease as the underlying cause of an increasing frequency of cardiac
      arrest in middle-aged men during marathons and ironman triathlons in the United
      States since the year 2000. Based on the high prevalence of subclinical coronary
      artery disease by cardiac computed tomography in endurance athletes with low
      conventional cardiac risk-factor profiles, we recommend coronary artery calcium
      scores as a more reliable and independent predictor of incident cardiac events,
      including death, as validated among adults aged 30-46 years. Scores of over 100
      Agatston units indicate a 10-year cardiac risk of 7.5%, at which additional
      measures for primary prevention are recommended, including aspirin, as shown
      conclusively to reduce first myocardial infarctions in same-aged men in a
      prospective double-blind controlled trial. Targeted screening for subclinical
      coronary atherosclerosis with coronary artery calcium scores is prudent to guide
      appropriately dosed aspirin use to mitigate the increasing frequency of sports
      related sudden cardiac death due to plaque rupture.

PMID- 30296407
TI  - Online Patient Education Materials for Orthognathic Surgery Fail to Meet
      Readability and Quality Standards.
AB  - PURPOSE: The purpose of this study was to evaluate the readability and quality of
      online patient educational materials (PEMs) for orthognathic surgery. MATERIALS
      AND METHODS: Two internet searches were performed using the search terms
      orthognathic surgery and jaw surgery. The presence of content related to the
      risks, benefits, procedure, and postoperative care was recorded. Readability was
      measured using 4 validated scales: Flesch-Kincaid grade level, Gunning Fog index,
      Coleman-Liau index, and Simple Measure of Gobbledygook index. Materials were
      readable if they were written at or below an eighth-grade reading level as
      recommended by the American Medical Association (AMA) and the National Institutes
      of Health (NIH). Quality was assessed using 2 metrics: the DISCERN instrument and
      the Journal of the American Medical Association benchmark criteria. A DISCERN
      score of 50 was set as the lower limit of acceptable quality. Mann-Whitney U and
      Fisher exact tests were used to compare the readability, quality, and presence of
      content between private practice and non-private practice PEMs. RESULTS: Fifty
      websites were included in the study after removing duplicates and applying
      exclusion criteria. On average, PEMs were written at a 13.4-grade level (range,
      7.8 to 17.3). Nearly every website (n = 49; 98%) mentioned the benefits of
      surgery; however, very few websites discussed the surgical procedure (n = 12;
      24%), postoperative care (n = 10; 20%), and risks or complications (n = 6; 12%).
      The mean DISCERN score was 25.5 of 80 (range, 18 to 63), and only 2 websites
      achieved DISCERN scores of acceptable quality. Private practice websites reported
      less content related to the surgical procedure (P = .03) and had lower DISCERN
      scores (P = .02). CONCLUSIONS: As a whole, online PEMs for orthognathic surgery
      failed to meet AMA and NIH readability recommendations and yielded poor quality
      scores. Increasing the presence of content related to treatment risks and
      postoperative care will help improve the quality of PEMs.

PMID- 30296408
TI  - Epigenetic upregulation of miR-126 induced by heat stress contributes to
      apoptosis of rat cardiomyocytes by promoting Tomm40 transcription.
AB  - TOMM40 is the channel-forming subunit of a translocase of the mitochondrial outer
      membrane (TOM) that is essential for protein transport into mitochondria. TOMM40
      plays an important role in maintaining normal mitochondrial function. The
      correlation between occupational thermal exposure and mitochondria dysfunction
      has been demonstrated; however, nothing is known about the alteration and role of
      TOMM40 in response to environmental heat stress. In the present study, we showed
      that environmental thermal exposure upregulated microRNA miR-126, consequently
      reducing AU-rich element RNA-binding protein 1 (AUF1)-mediated SP1 mRNA
      degradation and increasing TOMM40 transcription, which in turn decreased the
      mitochondria membrane potential and apoptosis of cardiomyocytes. Mechanistically,
      miR-126 upregulation was attributed to heat stress-induced promoter demethylation
      via elevated TET2 (Tet methylcytosine dioxygenase 2) expression, while SP1 mRNA
      degradation was caused by decreased translation of AUF1 induced by miR-126.
      Moreover, TOMM40 transcription was upregulated via increasing its transcription
      factor SP1 resulting from AUF1 inhibition in the heat stress responses. The
      results of the present study increased our understanding of the role of miR-126
      and TOMM40 in heat stressed cardiomyocytes.

PMID- 30296409
TI  - PARP inhibition induces Akt-mediated cytoprotective effects through the formation
      of a mitochondria-targeted phospho-ATM-NEMO-Akt-mTOR signalosome.
AB  - PURPOSE: The cytoprotective effect of poly(ADP-ribose) polymerase 1 (PARP1)
      inhibition is well documented in various cell types subjected to oxidative
      stress. Previously, we have demonstrated that PARP1 inhibition activates Akt, and
      showed that this response plays a critical role in the maintenance of
      mitochondrial integrity and in cell survival. However, it has not yet been
      defined how nuclear PARP1 signals to cytoplasmic Akt. METHODS: WRL 68, HeLa and
      MCF7 cells were grown in culture. Oxidative stress was induced with hydrogen
      peroxide. PARP was inhibited with the PARP inhibitor PJ34. ATM, mTOR- and NEMO
      were silenced using specific siRNAs. Cell viability assays were based on the MTT
      assay. PARP-ATM pulldown experiments were conducted; each protein was visualized
      by Western blotting. Immunoprecipitation of ATM, phospho-ATM and NEMO was
      performed from cytoplasmic and mitochondrial cell fractions and proteins were
      detected by Western blotting. In some experiments, a continually active Akt
      construct was introduced. Nuclear to cytoplasmic and mitochondrial translocation
      of phospho-Akt was visualized by confocal microscopy. RESULTS: Here we present
      evidence for a PARP1 mediated, PARylation-dependent interaction between ATM and
      NEMO, which is responsible for the cytoplasmic transport of phosphorylated (thus,
      activated) ATM kinase. In turn, the cytoplasmic p-ATM and NEMO forms complex with
      mTOR and Akt, yielding the phospho-ATM-NEMO-Akt-mTOR signalosome, which is
      responsible for the PARP-inhibition induced Akt activation. The phospho-ATM-NEMO
      Akt-mTOR signalosome localizes to the mitochondria and is essential for the PARP
      inhibition-mediated cytoprotective effects in oxidatively stressed cells. When
      the formation of the signalosome is prevented, the cytoprotective effects
      diminish, but cells can be rescued by constantly active Akt1, further confirming
      the critical role of Akt activation in cytoprotection. CONCLUSIONS: Taken
      together, the data presented in the current paper are consistent with the
      hypothesis that PARP inhibition suppresses the PARylation of ATM, which, in turn,
      forms an ATM-NEMO complex, which exits the nucleus, and combines in the cytosol
      with mTOR and Act, resulting in Act phosphorylation (i.e. activation), which, in
      turn, produces the cytoprotective action via the induction of Akt-mediated
      survival pathways. This mechanism can be important in the protective effect of
      PARP inhibitor in various diseases associated with oxidative stress. Moreover,
      disruption of the formation or action of the phospho-ATM-NEMO-Akt-mTOR
      signalosome may offer potential future experimental therapeutic checkpoints.

PMID- 30296410
TI  - Proteome variation of the rat liver after static cold storage assayed in an ex
      vivo model.
AB  - Cold storage is a common procedure for liver preservation in a transplant
      setting. However, during cold ischemia, the liver suffers molecular alterations
      that can affect its performance. Also, deleterious mechanisms set forth in the
      storage phase are exacerbated during reperfusion. This study aimed to identify
      liver proteins associated with injury during cold storage and/or normothermic
      reperfusion using the isolated perfused rat liver model. Livers from male rats
      were subjected to either (1) cold storage for 24 h, (2) ex vivo normothermic
      reperfusion for 90 min or (3) cold storage for 24 h followed by ex vivo
      normothermic reperfusion for 90 min. Then, the livers were homogenized and
      proteins were extracted. Protein expression between each experimental group and
      the control (freshly resected livers) was compared by two-dimensional (2D) gel
      electrophoresis. Protein identification was carried out by matrix-assisted laser
      desorption/ionization time-of-flight spectrometry (MALDI-TOF/TOF) using MASCOT as
      the search engine. 23 proteins were detected with significantly altered levels of
      expression among the different treatments, including molecular chaperones,
      antioxidant enzymes, and proteins involved in energy metabolism. Some of them
      have been postulated as biomarkers for liver damage while others had been
      identified in other organs subjected to ischemia and reperfusion injury. The
      whole data set will be a useful resource for studying deleterious molecular
      mechanisms that result in diminished liver function during storage and subsequent
      reperfusion.

PMID- 30296411
TI  - Properties of phase transition of ice binding protein from Arctic yeast (LeIBP)
      utilizing differential scanning calorimetry (DSC) and Raman spectroscopy.
AB  - Ice binding proteins (IBPs) have been attracting significant interest on account
      of their characteristic of inhibiting ice growth and recrystallization. Owing to
      their unique characteristics, IBPs have been studied for applications in food,
      pharmaceuticals, and medicine, as well as from a general scientific point of
      view. In this study, we have used differential scanning calorimetry (DSC) and
      Raman spectroscopy as tools to understand the ice binding activity of the Arctic
      yeast-originating extracellular ice binding glycoprotein (LeIBP) isolated from
      Leucosporidium sp. AY30. From the DSC results, an increase in the specific heat
      capacity was confirmed for 1 mg/mL LeIBP, which suggested that additional heat
      flow was required for the change in temperature. In addition, the temperature
      corresponding to the phase change of the solution was measured, and Raman
      spectroscopy was carried out on the frozen and molten phases, respectively. From
      the results of Raman analysis, we confirmed that the helical vibrations related
      to the ice binding sites on LeIBP were dramatically suppressed when the LeIBP
      solution was frozen. Furthermore, principal component analysis (PCA) of the Raman
      spectra yielded the contrast factor between the freezing and melting states. Both
      DSC and Raman spectroscopy are widely used to study the ice binding activity and
      the structural changes associated with molecular vibrations in cryobiology.

PMID- 30296412
TI  - Light-induced generation and toxicity of docosahexaenoate-derived oxidation
      products in retinal pigmented epithelial cells.
AB  - Oxidative cleavage of docosahexaenoate (DHA) in retinal pigmented epithelial
      (RPE) cells produces 4-hydroxy-7-oxohept-5-enoic acid (HOHA) esters of 2
      lysophosphatidylcholine (PC). HOHA-PC spontaneously releases a membrane-permeant
      HOHA lactone that modifies primary amino groups of proteins and ethanolamine
      phospholipids to produce 2-(omega-carboxyethyl)pyrrole (CEP) derivatives. CEPs
      have significant pathological relevance to age-related macular degeneration (AMD)
      including activation of CEP-specific T-cells leading to inflammatory M1
      polarization of macrophages in the retina involved in "dry AMD" and TLR2
      dependent induction of angiogenesis that characterizes "wet AMD". RPE cells
      accumulate DHA from shed rod photoreceptor outer segments through phagocytosis
      and from plasma lipoproteins secreted by the liver through active uptake from the
      choriocapillaris. As a cell model of light-induced oxidative damage of DHA
      phospholipids in RPE cells, ARPE-19 cells were supplemented with DHA, with or
      without the lipofuscin fluorophore A2E. In this model, light exposure, in the
      absence of A2E, promoted the generation HOHA lactone-glutathione (GSH) adducts,
      depletion of intracellular GSH and a competing generation of CEPs. While DHA-rich
      RPE cells exhibit an inherent proclivity toward light-induced oxidative damage,
      photosensitization by A2E nearly doubled the amount of lipid oxidation and
      expanded the spectral range of photosensitivity to longer wavelengths. Exposure
      of ARPE-19 cells to 1 MUM HOHA lactone for 24 h induced massive (50%) loss of
      lysosomal membrane integrity and caused loss of mitochondrial membrane potential.
      Using senescence-associated beta-galactosidase (SA beta-gal) staining that
      detects lysosomal beta-galactosidase, we determined that exposure to HOHA lactone
      induces senescence in ARPE-19 cells. The present study shows that products of
      light-induced oxidative damage of DHA phospholipids in the absence of A2E can
      lead to RPE cell dysfunction. Therefore, their toxicity may be especially
      important in the early stages of AMD before RPE cells accumulate lipofuscin
      fluorophores.

PMID- 30296413
TI  - Letter to the editor announcing the availability of RCS and transgenic rats with
      P23H and S334ter rhodopsin mutations with inherited retinal degenerations.

PMID- 30296414
TI  - Molecular recognition of lipopolysaccharide by the lantibiotic nisin.
AB  - Nisin is a lanthionine antimicrobial effective against diverse Gram-positive
      bacteria and is used as a food preservative worldwide. Its action is mediated by
      pyrophosphate recognition of the bacterial cell wall receptors lipid II and
      undecaprenyl pyrophosphate. Nisin/receptor complexes disrupt cytoplasmic
      membranes, inhibit cell wall synthesis and dysregulate bacterial cell division.
      Gram-negative bacteria are much more tolerant to antimicrobials including nisin.
      In contrast to Gram-positives, Gram-negative bacteria possess an outer membrane,
      the major constituent of which is lipopolysaccharide (LPS). This contains surface
      exposed phosphate and pyrophosphate groups and hence can be targeted by nisin.
      Here we describe the impact of LPS on membrane stability in response to nisin and
      the molecular interactions occurring between nisin and membrane-embedded LPS from
      different Gram-negative bacteria. Dye release from liposomes shows enhanced
      susceptibility to nisin in the presence of LPS, particularly rough LPS chemotypes
      that lack an O-antigen whereas LPS from microorganisms sharing similar ecological
      niches with antimicrobial producers provides only modest enhancement. Increased
      susceptibility was observed with LPS from pathogenic Klebsiella pneumoniae
      compared to LPS from enteropathogenic Salmonella enterica and gut commensal
      Escherichia coli. LPS from Brucella melitensis, an intra-cellular pathogen which
      is adapted to invade professional and non-professional phagocytes, appears to be
      refractory to nisin. Molecular complex formation between nisin and LPS was
      studied by solid state MAS NMR and revealed complex formation between nisin and
      LPS from most organisms investigated except B. melitensis. LPS/nisin complex
      formation was confirmed in outer membrane extracts from E. coli.

PMID- 30296415
TI  - Oxidatively stressed mitochondria-mimicking membranes: A molecular insight into
      their organization during apoptosis.
AB  - Mitochondria are crucially involved in the removal of eukaryotic cells by the
      intrinsic pathway of programmed cell death (apoptosis). The mitochondrion's outer
      membrane (MOM) is the platform where this pathway takes place. Upon oxidative
      stress triggering apoptotic action, the MOM undergoes permeabilization and
      release of cytochrome c, ultimately causing cell death. This membrane perforation
      is regulated not only by opposing members of the Bcl-2 protein family meeting at
      the MOM but also actively the membrane itself. Upon oxidative damage, the
      membrane undergoes severe reorganization causing an increase in cell death
      causing apoptotic Bcl-2 proteins. To understand the active role of MOM, we
      provided a detailed molecular view of its structural and dynamic reorganization
      upon oxidative stress by solid-state 13C MAS NMR (magic angle spinning nuclear
      magnetic resonance) accompanied by calorimetric studies. By focusing on MOM-like
      vesicles doped with oxidized lipid species, direct polarization 13C MAS NMR
      provided a quantitative overview and identification of all lipid moieties across
      the membrane. 1H-13C cross polarization and insensitive nuclei enhanced by
      polarization transfer MAS NMR generated a dynamic - mobile versus restricted -
      membrane profile. Oxidized phospholipids significantly perturb the structural
      membrane organization and increase membrane dynamics. These perturbations are not
      uniformly distributed as the hydrophobic core is reflecting the melting of lipid
      chains and increase in molecular disorder directly, whereas the interface and
      headgroup region undergo complex dynamical changes, reflecting increased intra
      molecular flexibility of these moieties. These changes are potentially crucial in
      augmenting pro-apoptotic action of proteins like Bax.

PMID- 30296416
TI  - A 52-Week Study of Dose-Adjusted Subcutaneous Testosterone Enanthate in Oil Self
      Administered via Disposable Auto-injector.
AB  - PURPOSE: This open-label, single-arm, dose-blinded, 52-week, registration-phase
      study evaluated the efficacy and safety of subcutaneous testosterone enanthate
      auto-injector (SCTE-AI) administered weekly to men with hypogonadism. METHODS:
      Patients (N=150) were initiated on 75 mg SCTE-AI self-administered weekly. Dose
      adjustments were made at week 7 to 50, 75, or 100 mg testosterone enanthate (TE)
      based on week 6 total testosterone (TT) trough concentration. If required, dose
      adjustments continued through the extended treatment phase. Pharmacokinetic (PK)
      and clinical laboratory parameters, treatment-emergent adverse events (TEAEs),
      and injection site reactions were captured. RESULTS: The primary endpoint was
      met: 92.7% of patients achieved an average TT concentration of 300-1100 ng/dL
      (553.3 +/- 127.29 ng/dL, mean +/- SD) at week 12. A Cmax of <1500 ng/dL was
      achieved by 91.3% of patients, and no patients had levels >1800 ng/dL at week 12.
      Mean TT Ctrough was 487.2 +/- 153.33 ng/dL at week 52. Most patients (>95%)
      reported no injection-related pain. The most frequently-reported TEAEs were
      increased hematocrit, hypertension, and increased prostate-specific antigen,
      which led to discontinuation in 30 men. There were no study drug-related serious
      AEs. DISCUSSION: Dose-adjusted SCTE-AI demonstrated a steady serum TT PK profile,
      with small peak and trough fluctuations. SCTE-AI was safe, well tolerated, and
      virtually painless, indicating that SCTE-AI offers a testosterone delivery system
      that is a convenient weekly option for treatment of testosterone deficiency.

PMID- 30296417
TI  - A similarity-based method for prediction of drug side effects with heterogeneous
      information.
AB  - Drugs can produce intended therapeutic effects to treat different diseases.
      However, they may also cause side effects at the same time. For an approved drug,
      it is best to detect all side effects it can produce. Otherwise, it may bring
      great risks for pharmaceuticals companies as well as be harmful to human body. It
      is urgent to design quick and reliable identification methods to detect the side
      effects for a given drug. In this study, a binary classification model was
      proposed to predict drug side effects. Different from most previous methods, our
      model termed the pair of drug and side effect as a sample and convert the
      original problem to a binary classification problem. Based on the similarity
      idea, each pair was represented by five features, each of which was derived from
      a type of drug property. The strong machine learning algorithm, random forest,
      was adopted as the prediction engine. The ten-fold cross-validation on five
      datasets with different negative samples indicated that the proposed model
      yielded a good performance of Matthews correlation coefficient around 0.550 and
      AUC around 0.8492. In addition, we also analyzed the contribution of each drug
      property for construction of the model. The results indicated that drug
      similarity in fingerprint was most related to the prediction of drug side effects
      and all drug properties gave less or more contributions.

PMID- 30296419
TI  - Impact of Ethylene Oxide Sterilization of Polymer-Based Prefilled Syringes on
      Chemical Degradation of a Model Therapeutic Protein During Storage.
AB  - Materials from prefilled syringe systems-such as silicone oil, tungsten, glass,
      and rubber-may enhance therapeutic protein aggregation and particle formation.
      Also, the sterilization method used for syringes may impact aggregation and
      chemical degradation of biologics during storage. Syringes are generally
      sterilized by radiation, ethylene oxide gas (EO), or steam. Among the
      sterilization methods, EO has the potential to cause chemical degradation by the
      formation of adducts with susceptible amino acid residues in the protein. In this
      study, EO- and steam-sterilized syringes were compared to determine the influence
      of residual EO on human serum albumin (HSA) degradation. Although the amount of
      residual EO in the EO-sterilized syringes was less than 220 MUg/syringe, well
      below the International Organization for Standardization limit, EO adduction to
      cysteine (Cys) and methionine (Met) in HSA was observed by liquid chromatography
      and mass spectrometry analysis. The EO adduct ratio of HSA stored for 2 weeks in
      EO-sterilized syringes was about 45%. In contrast, no chemical degradation was
      observed in HSA formulation stored in steam-sterilized syringes. Because of the
      propensity of EO to readily form adducts with proteins, an alternative to EO
      sterilization should be used for prefilled syringes that will be used for
      therapeutic protein products.

PMID- 30296418
TI  - Adult Outpatients With Acute Cough Due to Suspected Pneumonia or Influenza: CHEST
      Guideline and Expert Panel Report.
AB  - BACKGROUND: Patients commonly present to primary care services with upper and
      lower respiratory tract infections, and guidelines to help physicians investigate
      and treat acute cough due to suspected pneumonia and influenza are needed.
      METHODS: A systematic search was carried out with eight patient, intervention,
      comparison, outcome questions related to acute cough due to suspected pneumonia
      or influenza. RESULTS: There was a lack of randomized controlled trials in the
      setting of outpatients presenting with acute cough due to suspected pneumonia or
      influenza who were not hospitalized. Both clinical suggestions and research
      recommendations were made on the evidence available and CHEST Expert Cough Panel
      advice. CONCLUSIONS: For outpatient adults with acute cough due to suspected
      pneumonia, we suggest the following clinical symptoms and signs are suggestive of
      pneumonia: cough; dyspnea; pleural pain; sweating, fevers, or shivers; aches and
      pains; temperature >= 38 degrees C; tachypnea; and new and localizing chest
      examination signs. Those suspected of having pneumonia should undergo chest
      radiography to improve diagnostic accuracy. Although the measurement of C
      reactive protein levels strengthens both the diagnosis and exclusion of
      pneumonia, there was no added benefit of measuring procalcitonin levels in this
      setting. We suggest that there is no need for routine microbiological testing. We
      suggest the use of empiric antibiotics according to local and national guidelines
      when pneumonia is suspected in settings in which imaging cannot be performed.
      Where there is no clinical or radiographic evidence of pneumonia, we do not
      suggest the routine use of antibiotics. There is insufficient evidence to make
      recommendations for or against specific nonantibiotic, symptomatic therapies.
      Finally, for outpatient adults with acute cough and suspected influenza, we
      suggest that initiating antiviral treatment (according to Centers for Disease
      Control and Prevention advice) within 48 hours of symptoms could be associated
      with decreased antibiotic use and hospitalization and improved outcomes.

PMID- 30296420
TI  - Dermal CD207-Negative Migratory Dendritic Cells Are Fully Competent to Prime
      Protective, Skin Homing Cytotoxic T-Lymphocyte Responses.
AB  - Dendritic cells (DCs) are important inducers and regulators of T-cell responses.
      They are able to activate and modulate the differentiation of CD4+ and CD8+ T
      cells. In the skin, there are at least five phenotypically distinct DC
      subpopulations that can be distinguished by differential expression of the cell
      surface markers CD207, CD103, and CD11b. Previous studies have suggested that
      dermal CD11b-CD207+ conventional type 1 DCs are indispensable for the priming of
      a skin homing cytotoxic T-lymphocyte response. However, conventional type 1 DCs
      are also the only skin DC subset capable of cross-presenting exogenous antigens
      on major histocompatibility complex class I. Thus, it remained unclear whether
      for antigens that do not require cross-presentation, such as viruses that infect
      DCs, other DC subtypes in the skin can contribute to cytotoxic T-lymphocyte
      priming. To address this question, we used a transgenic mouse model that allows
      inducible expression and presentation of a model antigen on selected subsets of
      dermal DCs. We show that for antigens presented via the conventional major
      histocompatibility complex class I presentation pathway, CD207- dermal DCs are
      fully competent to prime a skin homing cytotoxic T-lymphocyte response that is
      capable of protection against a local virus challenge and gives rise to skin
      resident memory CD8+ T cells.

PMID- 30296421
TI  - Outcomes of valve repair for degenerative disease in patients with mitral annular
      calcification.
AB  - BACKGROUND: The predictors for the development of MAC in degenerative mitral
      valve disease and the effect it may have on patient- and valve-related outcomes
      require further evaluation. METHODS: Between 1/2002 and 12/2015, 627 patients
      underwent mitral valve surgery for degenerative disease. MAC was seen in 75 (12%)
      patients; 73 (97%) underwent valve repair (6 without annuloplasty ring
      implantation) while 2 (3%) underwent valve replacement after an unsuccessful
      repair attempt. RESULTS: MAC was linked to patient age, female gender and
      degenerative disease subtype. Early mortality was comparable between patients
      with and without MAC [3/75 (4%) vs. 10/552 (2%), P=0.20]. In patients with MAC,
      1/3 deaths was directly related to annular decalcification and reconstruction.
      Early repair failure was more common in patients with MAC [8/75 (11%) vs. 17/552
      (3%), P=0.006]. During follow-up, no differences in overall survival or freedom
      from late reintervention were observed. However, at 8 years after surgery,
      freedom from recurrent mitral regurgitation was worse in patients with MAC. In
      these patients, repair failure was linked to non-use of ring annuloplasty. For
      patients with MAC in whom annular decalcification and annuloplasty were
      performed, repair durability was comparable to patients without MAC. CONCLUSIONS:
      Mitral valve surgery in degenerative disease accompanied by MAC is safe. Optimal
      surgical strategy includes annular decalcification (when this would prevent
      implantation of an annuloplasty ring) and ring annuloplasty and will lead to
      results similar to patients without MAC. However, when the annulus is not
      addressed, repair performance is hampered. For these patients, alternative repair
      techniques should be explored in the future.

PMID- 30296422
TI  - Comparison of Laparoscopic Versus Open Surgical Management of Morgagni Hernia.
AB  - BACKGROUND: Morgagni hernias are rare congenital diaphragmatic hernias that often
      do not become clinically significant until adulthood. The purpose of this study
      was to characterize the preoperative findings and describe surgical outcomes of
      Morgagni hernia repair based on operative approach. METHODS: Charts of patients
      who underwent repair of a Morgagni hernia were retrospectively reviewed from 1987
      to 2015. Medical records were reviewed for demographics, symptoms, comorbidities,
      surgical approach, hospital course, complications, and preoperative imaging.
      RESULTS: Forty-three cases were identified, 23 male and 20 female. Median age was
      50.4 years, and median body mass index was 33.1 kg/m2. Most common presenting
      symptoms were respiratory (35.7%) and gastrointestinal (28.6%). Although 83.3% of
      cases were newly diagnosed, none required emergent repair. Preoperative imaging
      demonstrated an average hernia size of 8.2 cm. Surgical approaches included
      laparotomy (62.8%), laparoscopic (23.3%), and thoracotomy (14%). Primary hernia
      repair was most common (72%). Comparing laparotomy, thoracotomy, and laparoscopic
      approaches, mesh repair was more common with laparoscopy (p = 0.005), operative
      time was shortest with laparotomy (p = 0.029), and hospital length of stay was
      shortest with laparoscopy (p = 0.024). The most common complication was
      incisional/port site hernia, with no statistical significance between surgical
      approaches. There was one Morgagni hernia recurrence. CONCLUSIONS: Morgagni
      hernias often present with respiratory and gastrointestinal symptoms and require
      repair. All cases in our series were repaired electively. Regardless of approach
      recurrence rate was low (2.3%) and complication rate was similar between
      laparoscopic, laparotomy, and thoracotomy. Given the shorter length of stay with
      similar recurrence rates, a laparoscopic approach is a viable option for repair
      of Morgagni hernia.

PMID- 30296423
TI  - Intraoperative Near-Infrared Fluorescence-Guided Peripheral Lung Tumor
      Localization in Rabbit Models.
AB  - BACKGROUND: A novel liposomal nanoparticle, CF800, that co-encapsulates
      indocyanine green for near-infrared (NIR) imaging and iohexol for computed
      tomography (CT) imaging has shown preferential tumor accumulation after
      intravenous injection by the enhanced permeability and retention effect. We
      hypothesized that CF800-enhanced NIR imaging would facilitate intraoperative
      localization of small lung nodules. METHODS: A rabbit VX2 lung tumor model was
      implemented. CF800 was injected intravenously, followed by sequential CT
      acquisitions to track the biodistribution of CF800. Eleven rabbits were used for
      NIR fluorescence evaluation after thoracotomy at time points until 7 days after
      injection by using a NIR fluorescence thoracoscope in vivo. Organs of interests
      were removed for ex vivo analysis by using NIR imaging. Tumor-to-background
      (inflated lung) ratio was calculated and compared among the time points. RESULTS:
      Both CT and NIR imaging indicated enhanced accumulation of CF800 within the VX2
      tumor. NIR image analysis revealed the highest tumor-to-background ratio on days
      4 and 5. High background at day 2 and low tumor signal at day 7 prevented
      distinct demarcation. Metastatic pulmonary small nodules (less than 2 mm in
      diameter) were successfully visualized by NIR imaging on day 4. However, NIR
      signal penetration was limited, resulting in localization failure for the few
      tumors deep (>0 mm) to the lung surface. CONCLUSIONS: NIR image-guided
      localization of small lung nodules appears to be feasible under certain
      conditions. However, further refinement will be required to increase tumor signal
      intensity and to reduce background signal from normal lung parenchyma, which is
      at least in part a consequence of persistent CF800 in the vasculature.

PMID- 30296424
TI  - Initial Experiences With Robotic Single-Site Thoracic Surgery for Mediastinal
      Masses.
AB  - BACKGROUND: The da Vinci Single-Site platform (Intuitive Surgical, Mountain View,
      CA) has been applied in many fields of surgery, but use of this single-site
      platform in thoracic surgery has not been reported. This study reported our
      experiences and surgical outcomes with robotic single-site surgery in the field
      of thoracic surgery. METHODS: We retrospectively reviewed 14 patients who
      underwent robotic single-site thoracic surgery at 2 different institutions.
      RESULTS: All 14 cases were successfully completed, without conversion to
      conventional multiport robotic surgery. The most frequent diagnoses were thymic
      cyst (n = 4) and pericardial cyst (n = 3). The median largest mass size was 4.1
      cm (range, 2.0 to 6.5 cm). The median operation time was 105 minutes (range, 27
      to 185 minutes). After the operation, pleural effusion occurred in 1 patient
      (case 7) on the side on which the operation was performed but was managed with
      conservative treatment. The median duration of chest tube stay was 2 days (range,
      1 to 3 days), and hospital stay was 4 days (range, 3 to 11 days). The median peak
      pain score after the operation was 3 (range, 1 to 7). Compared with thoracoscopic
      single-port surgery, robotic single-site thoracic surgery showed a longer
      operative time and higher cost. CONCLUSIONS: This study demonstrated that robotic
      single-site thoracic surgery for mediastinal masses is a safe and feasible
      procedure. Although this study reports the initial series and the cases were
      relatively simple, more advanced and complex procedures could be done with the
      advent of new technology in the near future.

PMID- 30296425
TI  - Ventricular Assist Device Support: Single Pediatric Institution Experience Over
      Two Decades.
AB  - BACKGROUND: We sought to review our single institutional experience with
      pediatric ventricular assist device (VAD) support over the last two decades, with
      an aim to improve our current management and to gain an insight into the future
      direction. METHODS: A retrospective review was conducted on all patients that had
      undergone VAD support between 1996 and 2017. Outcomes were analyzed based on the
      type of VADs, whether temporary or durable devices. Primary endpoints were
      positive outcomes including bridge-to-transplantation (BTT), bridge-to-recovery
      (BTR), alive on device, and bridge-to-bridge to another VAD (BTB) or negative
      outcomes including death during VAD support or in-hospital death following BTR.
      PediMACS definition was utilized to classify adverse events. RESULTS: Overall,
      201 VADs were implanted in 159 patients, with 82 (41%) and 119 (59%) being
      temporary and durable support, respectively. There has been a trend toward an
      increasing annual implant volume both with temporary and durable VADs. 80%
      (66/82) of temporary support achieved positive outcomes, with BTR (53%, 35/66)
      and BTB (38%, 25/66) being the predominant outcomes. 84% (100/119) of durable
      support achieved positive outcomes, with BTT (66%, 78/119) being the leading
      destination. The most notable change during the study period was the introduction
      of implantable continuous-flow VADs, resulting in outpatient management becoming
      a routine practice. While none were discharged on VAD support before 2004, 85%
      were discharged on VADs with discharge capability after 2013. CONCLUSIONS: The
      present study has demonstrated the evolutional changes of pediatric VAD support
      and their impact on clinical outcomes over the last two decades.

PMID- 30296426
TI  - Measuring What Matters.

PMID- 30296427
TI  - The cytosolic Ca2+ concentration in acutely dissociated subfornical organ (SFO)
      neurons of rats: spontaneous Ca2+ oscillations and Ca2+ oscillations induced by
      picomolar concentrations of angiotensin II.
AB  - Characteristics of subfornical organ (SFO) neurons were examined by measuring the
      cytosolic Ca2+ concentration ([Ca2+]i) in acutely dissociated neurons of the rat.
      SFO neurons, defined by the responsiveness to 50 mM K+ (n=67) responded to
      glutamate (86%), angiotensin II (AII) (50%), arginine vasopressin (AVP) (66%)
      and/or carbachol (CCh) (61%), at their maximal concentrations, with marked
      increases in [Ca2+]i. More than a half (174/307) of SFO neurons examined
      exhibited spontaneous Ca2+ oscillations, while the remainder showed a relatively
      stable baseline under unstimulated conditions. Spontaneous Ca2+ oscillations were
      suppressed when extracellular Ca2+ was removed and were inhibited when
      extracellular Na+ was replaced with equimolar Nmethyl- D-glucamine. Ca2+
      oscillations were unaffected by the inhibitor of Ca2+-dependent ATPases
      cyclopiazonic acid, the N-type Ca2+ channel blocker omega-conotoxin GVIA and the
      P/Q-type Ca2+ channel blocker omega-agatoxin IVA, but significantly inhibited by
      the high-voltage-activated Ca2+ channel blocker Cd2+ and the L-type Ca2+ channel
      blocker nicardipine. Ca2+ oscillations were also completely arrested by the
      voltage-gated Na+ channel blocker tetrodotoxin in 50 % of SFO neurons but only
      partially in the remaining neurons. These results suggest that SFO neurons
      exhibit spontaneous membrane Ca2+ oscillations that are dependent in part on Ca2+
      entry through L-type Ca2+ channels, whose activation may result from burst
      firing. Moreover, AII at picomolar concentrations induced Ca2+ oscillations in
      neurons showing no spontaneous Ca2+ oscillations, while spontaneous Ca2+
      oscillations were arrested by gamma-aminobutyric acid (10 MUM), suggesting that
      rises in [Ca2+]i during Ca2+ oscillations may play an important role in the
      modulation of SFO neuron function.

PMID- 30296428
TI  - Cell type- and pathway-specific synaptic regulation of orexin neurocircuitry.
AB  - Orexin-expressing neurons are located exclusively in the lateral hypothalamic and
      perifornical areas and exhibit complex connectivity. The intricate wiring pattern
      is evident from a diverse function for orexin neurons in regulating many
      physiological processes and behaviors including sleep, metabolism, circadian
      cycles, anxiety, and reward. Nevertheless, the precise synaptic and circuitry
      level mechanisms mediating these processes remain enigmatic, partially due to the
      wide spread connectivity of the orexin system, complex neurochemistry of orexin
      neurons, and previous lack of suitable tools to address its complexity. Here we
      summarize recent advances, focusing on synaptic regulatory mechanisms in the
      orexin neurocircuitry, including both the synaptic inputs to orexin neurons as
      well as their downstream targets in the brain. A clear and detailed elucidation
      of these mechanisms will likely provide novel insight into how dysfunction in
      orexin-mediated signaling leads to human disease and may ultimately be treated
      with more precise strategies.

PMID- 30296429
TI  - Plasma Levels of Brain-Derived Neurotrophic Factor in Patients with Parkinson
      Disease: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is an abundant neurotrophin
      in the adult brain. Serum BDNF levels might be used as a proxy for its central
      expression. Considering conflicting reports, we aimed to answer "How do serum/CSF
      levels of BDNF change in patients with PD?". METHODS: We conducted a
      comprehensive search in MEDLINE, EMBASE and SCOPUS databases including 12
      eligible studies. Five studies compared BDNF in serum of PD patients versus
      healthy controls (HC) and 3 studies provided BDNF levels in sera of non-depressed
      and depressed PD patients (NDPD and DPD). Review Manager and Software version 3.0
      were used for meta-analysis and meta-regressions. Mean difference (MD) was used
      for measurement of effect size. RESULTS: PD patients had reduced serum BDNF
      levels compared to HC (MD=-2.99 ng/mL). Serum BDNF was highest in DPD patients
      compared to HC (MD=-4.83 ng/mL), with no difference between DPD and NDPD patients
      in serum BDNF levels. Among co-variates that were eligible for meta-regression,
      age, sex, and Hoehn and Yahr (H&Y) motor stage had significant positive
      associations with the effect size in the difference of serum BDNF between
      patients and HC. CONCLUSIONS: PD patients had reduced serum BDNF levels compared
      to HC, regardless of presence of co-morbid depression. PD is at least equally
      effective in reducing serum BDNF levels as depression. Motor progression predicts
      serum BDNF downregulation in PD. Acute exercise improves motor function and
      depressive symptoms in PD probably via BDNF upregulation. The paradoxical rise in
      serum BDNF in advance PD is probably compensatory in nature.

PMID- 30296430
TI  - Long-Term Deficits in Risky Decision-Making after Traumatic Brain Injury on a Rat
      Analog of the Iowa Gambling Task.
AB  - Traumatic brain injury (TBI) affects 2.8 million people annually in the United
      States, with significant populations suffering from ongoing cognitive
      dysfunction. Impairments in decision-making can have major implications for
      patients and their caregivers, often enduring for years to decades, yet are
      rarely explored in experimental TBI. In the current study, the Rodent Gambling
      Task (RGT), an Iowa Gambling Task analog, was used to assess risk-based decision
      making and motor impulsivity after TBI. During testing, rats chose between
      options associated with different probabilities of reinforcement (sucrose) or
      punishment (timeout). To determine effects of TBI on learned behaviors versus the
      learning process, rats were trained either before, or after, a bilateral frontal
      controlled cortical impact TBI, and then assessed for 12 weeks. To evaluate the
      degree to which monoamine systems, such as dopamine, were affected by TBI, rats
      were given an amphetamine challenge, and behavior recorded. Injury immediately
      and chronically decreased optimal decision-making, and biased rats towards both
      riskier, and safer (but suboptimal) choices, regardless of prior learning
      history. TBI also increased motor impulsivity across time, reflecting ongoing
      neural changes. Despite these similarities in trained and acquisition rats, those
      that learned the task after injury demonstrated reduced effects of amphetamine on
      optimal decision-making, suggesting a lesser role of monoamines in post-injury
      learning. Amphetamine also dose-dependently reduced motor impulsivity in injured
      rats. This study opens up the investigation of psychiatric-like dysfunction in
      animal models of TBI and tasks such as the RGT will be useful in identifying
      therapeutics for the chronic post-injury period.

PMID- 30296431
TI  - Factors Associated With Recurrence of Primary Biliary Cholangitis After Liver
      Transplantation and Effects on Graft and Patient Survival.
AB  - BACKGROUND & AIMS: Primary biliary cholangitis (PBC) frequently recurs after
      liver transplantation. We evaluated risk factors associated with recurrence of
      PBC and its effects on patient and graft survival in a multicenter, international
      cohort (the Global PBC Study Group). METHODS: We collected demographic and
      clinical data from 785 patients (89% female) with PBC who underwent liver
      transplantation (mean age, 54 +/- 9 years) from February 1983 through June 2016,
      among 13 centers in North America and Europe. Results from biochemical tests
      performed within 12 months of liver transplantation were analyzed to determine
      whether markers of cholestasis could identify patients with recurrence of PBC
      (based on histologic analysis). Patients were followed for a median 6.9 years
      (interquartile range, 6.1-7.9 years). RESULTS: PBC recurred in 22% of patients
      after 5 years and 36% after 10 years. Age at diagnosis <50 years (hazard ratio
      [HR], 1.79; 95% CI, 1.36-2.36; P < .001), age at liver transplantation <60 years
      (HR, 1.39; 95% CI, 1.02-1.90; P = .04), use of tacrolimus (HR, 2.31; 95% CI, 1.72
      3.10; P < .001), and biochemical markers of severe cholestasis (bilirubin >=100
      MUmol or alkaline phosphatase >3-fold the upper limit of normal) at 6 months
      after liver transplantation (HR, 1.79; 95% CI, 1.16-2.76; P = .008) were
      associated with higher risk of PBC recurrence, whereas use of cyclosporine
      reduced risk of PBC recurrence (HR, 0.62; 95% CI, 0.46-0.82; P = .001). In
      multivariable Cox regression with time-dependent covariate, recurrence of PBC
      significantly associated with graft loss (HR, 2.01; 95% CI, 1.16-3.51; P = .01)
      and death (HR, 1.72; 95% CI, 1.11-2.65; P = .02). CONCLUSIONS: Younger age at the
      time of diagnosis with PBC or at liver transplantation, tacrolimus use, and
      biochemical markers of cholestasis after liver transplantation are associated
      with PBC recurrence. PBC recurrence reduces odds of graft and patient survival.
      Strategies are needed to prevent PBC recurrence or reduce its negative effects.

PMID- 30296433
TI  - Acute Respiratory Failure During Systemic Chemotherapy.

PMID- 30296432
TI  - Accuracy of the Narrow-Band Imaging International Colorectal Endoscopic
      Classification System in Identification of Deep Invasion in Colorectal Polyps.
AB  - BACKGROUND & AIMS: T1 colorectal polyps with at least 1 risk factor for
      metastasis to lymph node should be treated surgically and are considered
      endoscopically unresectable. Optical analysis, based on the Narrow-Band Imaging
      International Colorectal Endoscopic (NICE) classification system, is used to
      identify neoplasias with invasion of the submucosa that require endoscopic
      treatment. We assessed the accuracy of the NICE classification, along with other
      morphologic characteristics, in identifying invasive polyps that are
      endoscopically unresectable (have at least 1 risk factor for metastasis to lymph
      node). METHODS: We performed a multicenter, prospective study of data collected
      by 58 endoscopists, from 1634 consecutive patients (examining 2123 lesions) at 17
      university and community hospitals in Spain from July 2014 through June 2016. All
      consecutive lesions >10 mm assessed with narrow-band imaging were included. The
      primary end point was the accuracy of the NICE classification for identifying
      lesions with deep invasion, using findings from histology analysis as the
      reference standard. Conditional inference trees were fitted for the analysis of
      diagnostic accuracy. RESULTS: Of the 2123 lesions analyzed, 89 (4.2%) had
      features of deep invasion and 91 (4.3%) were endoscopically unresectable. The
      NICE classification system identified lesions with deep invasion with 58.4%
      sensitivity (95% confidence interval [CI], 47.5-68.8), 96.4% specificity (95% CI,
      95.5-97.2), a positive-predictive value of 41.6% (95% CI, 32.9-50.8), and a
      negative-predictive value of 98.1% (95% CI, 97.5-98.7). A conditional inference
      tree that included all variables found the NICE classification to most accurately
      identify lesions with deep invasion (P < .001). However, pedunculated morphology
      (P < .007), ulceration (P = .026), depressed areas (P < .001), or nodular mixed
      type (P < .001) affected accuracy of identification. Results were comparable for
      identifying lesions that were endoscopically unresectable. CONCLUSIONS: In an
      analysis of 2123 colon lesions >10 mm, we found the NICE classification and
      morphologic features identify those with deep lesions with >96% specificity-even
      in non-expert hands and without magnification. ClinicalTrials.gov number
      NCT02328066.

PMID- 30296434
TI  - Serologic Response to Helicobacter pylori Proteins Associated With Risk of
      Colorectal Cancer Among Diverse Populations in the United States.
AB  - BACKGROUND & AIMS: Previous studies reported an association of the bacteria
      Helicobacter pylori, the primary cause of gastric cancer, and risk of colorectal
      cancer (CRC). However, these findings have been inconsistent, appear to vary with
      population characteristics, and may be specific for virulence factor VacA. To
      more thoroughly evaluate the potential association of H pylori antibodies with
      CRC risk, we assembled a large consortium of cohorts representing diverse
      populations in the United States. METHODS: We used H pylori multiplex serologic
      assays to analyze serum samples from 4063 incident cases of CRC, collected before
      diagnosis, and 4063 matched individuals without CRC (controls) from 10
      prospective cohorts for antibody responses to 13 H pylori proteins, including
      virulence factors VacA and CagA. The association of seropositivity to H pylori
      proteins, as well as protein-specific antibody level, with odds of CRC was
      determined by conditional logistic regression. RESULTS: Overall, 40% of controls
      and 41% of cases were H pylori-seropositive (odds ratio [OR], 1.09; 95% CI, 0.99
      1.20). H pylori VacA-specific seropositivity was associated with an 11% increased
      odds of CRC (OR, 1.11; 95% CI, 1.01-1.22), and this association was particularly
      strong among African Americans (OR, 1.45; 95% CI, 1.08-1.95). Additionally, odds
      of CRC increased with level of VacA antibody in the overall cohort (P = .008) and
      specifically among African Americans (P = .007). CONCLUSIONS: In an analysis of a
      large consortium of cohorts representing diverse populations, we found serologic
      responses to H pylori VacA to associate with increased risk of CRC risk,
      particularly for African Americans. Future studies should seek to understand
      whether this marker is related to virulent H pylori strains carried in these
      populations.

PMID- 30296436
TI  - Thermal Ablation of Mucosal Defect Margins Reduces Adenoma Recurrence After
      Colonic Endoscopic Mucosal Resection.
AB  - BACKGROUND & AIMS: Colorectal cancer (CRC) can be prevented by colonoscopy and
      polypectomy. Endoscopic mucosal resection (EMR) is performed to remove large
      laterally spreading colonic lesions, which have a high risk of progression to
      CRC. Endoscopically invisible micro-adenomas at the margins of the EMR site might
      contribute to adenoma recurrence, which occurs in 15%-30% of patients who undergo
      surveillance. We aimed to determine the efficacy of adjuvant thermal ablation of
      the EMR mucosal defect margin in reducing polyp recurrence. METHODS: We performed
      a prospective study of 390 patients with large laterally spreading colonic
      lesions (>= 20 mm, n = 416) referred for EMR at 4 tertiary centers in Australia.
      After complete lesion excision by EMR, lesions were randomly assigned to thermal
      ablation of the post-EMR mucosal defect margin (n = 210) or no additional
      treatment (controls, n = 206). We performed surveillance colonoscopies with
      standardized photo documentation and biopsies of the scar after 5-6 months.
      Patient, procedure and lesion characteristics were similar between the groups.
      The primary endpoint was detection of lesion recurrence at first surveillance
      colonoscopy. RESULTS: A significantly lower proportion of patients who received
      thermal ablation of the post-EMR mucosal defect margin had evidence of recurrence
      at first surveillance colonoscopy (10/192, 5.2%) than controls (37/176, 21.0%) (P
      < .001). The relative risk of recurrence in the thermal ablation group was 0.25
      compared with the control group (95% CI, 0.13-0.48). Rates of adverse events were
      similar between the groups. CONCLUSIONS: In a multi-center randomized trial,
      thermal ablation of the post-EMR mucosal defect margin significantly reduced
      polyp recurrence at SC1, compared with no additional treatment. Routine
      implementation of this simple and safe technique could increase the utility of
      EMR, decrease surveillance burdens, and reduce morbidity and mortality from CRC.
      ClinicalTrials.gov no: NCT01789749.

PMID- 30296435
TI  - Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of
      Pancreatic Tumors in Mice.
AB  - BACKGROUND AND AIMS: Cells in pancreatic ductal adenocarcinoma (PDAC) undergo
      autophagy, but its effects vary with tumor stage and genetic factors. We
      investigated the consequences of varying levels of the autophagy-related 5 (Atg5)
      protein on pancreatic tumor formation and progression. METHODS: We generated mice
      that express oncogenic Kras in primary pancreatic cancer cells and have
      homozygous disruption of Atg5 (A5;Kras) or heterozygous disruption of Atg5 (A5+/
      ;Kras), and compared them with mice with only oncogenic Kras (controls).
      Pancreata were analyzed by histology and immunohistochemistry. Primary tumor
      cells were isolated and used to perform transcriptome, metabolome, intracellular
      calcium, extracellular cathepsin activity, and cell migration and invasion
      analyses. The cells were injected into wild-type littermates, and orthotopic
      tumor growth and metastasis were monitored. Atg5 was knocked down in pancreatic
      cancer cell lines using small hairpin RNAs; cell migration and invasion were
      measured, and cells were injected into wild-type littermates. PDAC samples were
      obtained from independent cohorts of patients and protein levels were measured on
      immunoblot and immunohistochemistry; we tested the correlation of protein levels
      with metastasis and patient survival times. RESULTS: A5+/-;Kras mice, with
      reduced Atg5 levels, developed more tumors and metastases, than control mice,
      whereas A5;Kras mice did not develop any tumors. Cultured A5+/-;Kras primary
      tumor cells were resistant to induction and inhibition of autophagy, had altered
      mitochondrial morphology, compromised mitochondrial function, changes in
      intracellular Ca2+ oscillations, and increased activity of extracellular
      cathepsin L and D. The tumors that formed in A5+/-;Kras mice contained greater
      numbers of type 2 macrophages than control mice, and primary A5+/-;Kras tumor
      cells had up-regulated expression of cytokines that regulate macrophage
      chemoattraction and differentiation into M2 macrophage. Knockdown of Atg5 in
      pancreatic cancer cell lines increased their migratory and invasive capabilities,
      and formation of metastases following injection into mice. In human PDAC samples,
      lower levels of ATG5 associated with tumor metastasis and shorter survival time.
      CONCLUSIONS: In mice that express oncogenic Kras in pancreatic cells,
      heterozygous disruption of Atg5 and reduced protein levels promotes tumor
      development, whereas homozygous disruption of Atg5 blocks tumorigenesis.
      Therapeutic strategies to alter autophagy in PDAC should consider the effects of
      ATG5 levels to avoid the expansion of resistant and highly aggressive cells.

PMID- 30296437
TI  - An Efficient Method for Cloning Gastrointestinal Stem Cells From Patients via
      Endoscopic Biopsies.

PMID- 30296438
TI  - Pancreatic mass and subcutaneous nodules.

PMID- 30296439
TI  - Once upon a time in the esophagus.

PMID- 30296440
TI  - Evaluation of the Siemens ADVIA Centaur high-sensitivity cardiac troponin I assay
      in serum.
AB  - BACKGROUND: International recommendations on high-sensitivity cardiac troponin
      (hs-cTn) testing recommend that laboratories select only one sample type for
      testing. We evaluated the Siemens ADVIA Centaur hs-cTnI assay in serum and
      thereby provide information on imprecision, long-term storage stability, freeze
      thaw stability, method comparison to other hs-cTnI assays, and clinical
      performance. METHODS: Patients with chest pain onset <6 h who already had Roche
      hs-cTnT, Beckman hs-cTnI and Abbott hs-cTnI results recorded and had non-thawed
      and frozen serum aliquots formed the study population (n = 134 patients with 305
      serum aliquots obtained at either 0, 3 or 6 h stored below -70  degrees C since
      2003) for measurement with the Siemens hs-cTnI assay in 2018. Receiver-operating
      characteristic curve analyses for myocardial infarction (MI) using the highest
      obtained hs-cTn concentration was performed. Additional comparison testing on
      serum samples stored frozen (at -70  degrees C for <1 month in 2018) for the
      Siemens and Abbott hs-cTnI assays were performed, as well as precision testing in
      serum pools and freeze-thaw stability testing. RESULTS: The Siemens hs-cTnI assay
      had an area under the curve (AUC) of 0.978 (95%CI: 0.937-0.996) for MI in the
      study cohort (Roche hs-cTnT AUC = 0.965 and Abbott AUC = 0.973). The Siemens hs
      cTnI assay yielded higher cTnI concentrations than the other hs-cTn assays, with
      the same proportional bias (slope = 1.4) between the Siemens and Abbott hs-cTnI
      assays obtained from serum samples collected in 2003 and 2018. Over 3 months, a
      low serum pool of 3.5 ng/l achieved a CV of 20% (SD = 0.7, n = 42) and a high
      serum pool of 820 ng/l achieved a CV of 2.3% (SD = 20, n = 42). Three different
      serum pools recovered within 10% from baseline concentration after 5 freeze-thaw
      cycles for the Siemens hs-cTnI assay. CONCLUSIONS: In serum, the Siemens ADVIA
      Centaur hs-cTnI assay had excellent clinical performance for MI in an early chest
      pain onset population, acceptable precision at normal and highly elevated cTnI
      concentrations, long-term storage stability (15 y storage below -70  degrees C)
      and acceptable freeze-thaw stability, all of which supports serum as an
      acceptable sample type to use in clinical studies and in clinical practice.

PMID- 30296441
TI  - Characterization of PLAC(r) tests in the quantization of lipoprotein associated
      phospholipase A2 for assessment of cardiovascular diseases.
AB  - BACKGROUND: PLAC(r) mass test (diaDexus, Inc.) does not detect all Lp-PLA2
      proteins in the circulation. The total circulating Lp-PLA2 mass can be quantized
      by using the CHAPS modified PLAC(r) mass test. To compare the difference of the
      PLAC(r) mass, CHAPS modified PLAC(r) mass and PLAC(r) activity tests in risk
      assessment of CVD, the 3 Lp-PLA2 quantization methods were characterized using a
      collection of serum and plasma from CVD patents and matched non-symptomatic
      controls. Improvement on risk assessment for ischemic stroke by Lp-PLA2 and
      lipids were also investigated. METHODS: Ninety one human sera and plasma from
      elderly patients with first CVD incidents and 78 matched controls were collected
      at clinics. Lp-PLA2 was assessed by PLAC(r) mass, CHAPS modified PLAC(r) mass and
      PLAC(r) activity tests and data were subjected to statistical analyses.
      Correlation with lipid cholesterols or Apo proteins was compared for all formats
      of PLAC(r) tests. Ratios of Lp-PLA2 by different PLAC(r) tests to different
      lipids were assessed for synergistic enhancement in the indication of ischemic
      stroke. RESULTS: The PLAC(r) mass test was superior to other formats of PLAC(r)
      tests in the assessment of CVD and is independent of lipids. The Lp-PLA2 by the
      CHAPS modified PLAC(r) mass test has no separation between the CVD and control
      groups. CONCLUSIONS: Both PLAC(r) mass and PLAC(r) activity tests are effective
      but the CHAPS modified PLAC(r) mass test has no or less utility in the risk
      assessment of CVD. The ratio of Lp-PLA2 by either PLAC(r) mass or PLAC(r)
      activity over ApoA1 or (Apo A1 + Apo B) synergistically enhance the risk
      assessment power for ischemic stroke.

PMID- 30296442
TI  - Comprehensive assessment of biotin interference in immunoassays.
AB  - BACKGROUND: Biotinylated antibodies and analogues are currently used in many
      immunoassays while biotin is widely used as a dietary supplement. Thus, biotin
      interference is an emerging issue for clinical laboratories. METHODS: Various
      concentrations of biotin solutions were prepared using pooled patient serum
      samples. All analytes were measured by sandwich or competitive immunoassay on the
      Roche Cobas 8000 e602 platform. RESULTS: Some of the sandwich immunoassay results
      were falsely decreased to different extents by different biotin levels, while
      some of the competitive immunoassay results were falsely increased. The most
      notable false reductions were in high-sensitivity troponin T, thyroid-stimulating
      hormone, and follicle-stimulating hormone results, while the most notable false
      increases were in triiodothyronine and vitamin D results. Other immunoassay
      results were also affected to some extent by biotin interference. CONCLUSIONS:
      Biotin can interfere in immunoassays and result in aberrant test results.
      Clinicians should use caution in interpreting abnormal results in patients who
      ingest biotin.

PMID- 30296443
TI  - Apelin/APJ system: A novel promising target for anti-aging intervention.
AB  - Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is widely
      expressed in various organs. Recent research has indicated that the Apelin/APJ
      system plays an important role in aging. Apelin and APJ receptor expression are
      down-regulated with increasing age. In murine models, Apelin and APJ knockouts
      exhibit accelerated senescence whereas Apelin-restoration results in enhanced
      vigor and rejuvenated behavioral and circadian phenotypes. Furthermore, aged
      Apelin knockout mice develop progressive impairment of cardiac contractility
      associated with systolic dysfunction. Apelin is crucial to maintain cardiac
      contractility in aging. Moreover, the Apelin/APJ system appears to be involved in
      regulation of renin-angiotensin-aldosterone system (RAAS), apoptosis,
      inflammation and oxidative stress which promotes aging. Likewise, the Apelin/APJ
      system regulates autophagy, stem cells and the sirtuin family thus contributing
      to anti-aging. In this review, we describe the relationship between Apelin/APJ
      system and aging. We elaborate on the role of the Apelin/APJ system in aging
      stimulators, aging inhibitors and age-related diseases such as obesity, diabetes
      and cardiovascular disease. We conclude that Apelin/APJ system might become a
      novel promising therapeutic target for anti-aging.

PMID- 30296444
TI  - Plasma metabolomic profiling distinguishes right-sided from left-sided colon
      cancer.
AB  - BACKGROUND: Many studies have demonstrated that right-sided colon cancer (RCC)
      has a higher mortality rate and worse prognosis than left-sided colon cancer
      (LCC). However, the underlying biological mechanism that can account for these
      differences is unclear. METHODS: In this study, plasma metabolic profiles in 147
      LCC patients and 105 RCC patients were systematically analyzed by the ultra high
      performance liquid chromatography quadruple time-of-flight mass spectrometry
      (UHPLC-QTOF/MS) platform in conjunction with univariate and multivariate
      statistical analysis. RESULTS: Metabolic signatures revealed considerable
      differences between patients with RCC and LCC, and clear separations were
      observed between the two groups in partial least-squares discriminant analysis
      score plots. In total, six metabolites were identified as potential metabolite
      markers for tumor location in RCC compared with LCC, including upregulated
      trimethylamine N-oxide and indoxyl sulfate, and downregulated anserine, L
      targinine, gamma-glutamyl-gamma-aminobutyraldehyde and pyridoxal 5'-phosphate.
      These differences highlight that significant alternations occur in the pathways
      of methane metabolism, arginine and proline metabolism, histidine metabolism,
      beta-alanine metabolism and vitamin B6 metabolism in RCC compared with LCC.
      CONCLUSIONS: Identified biomarkers and metabolic pathways may facilate our
      understanding of the different mortality rates and prognoses between RCC and LCC.

PMID- 30296445
TI  - Harsh environments: Multi-player cooperation with excludability and congestion.
AB  - The common-enemy hypothesis of by-product mutualism proposes that organisms are
      more likely to cooperate when facing the common enemy of a harsher environment.
      Micro-foundations of this hypothesis have so far focused on the case where
      cooperation consists of the production of a pure public good. In this case, the
      effect of a harsher environment is ambiguous: not only a common-enemy effect is
      possible, but also an opposite, competing effect where the harsher environment
      reduces the probability of cooperation. This paper shows that unambiguous effects
      of a harsher environment are predicted when considering the realistic case where
      the collective good produced is excludable (in the sense that whether or not a
      player benefits from the collective good depends on whether or not he is
      contributing) and/or congestible (in the sense that the benefits the individual
      player obtains from the collective good are affected by the number of
      contributing players). In particular, the competing effect is systematically
      predicted for club goods, where defectors are excluded from the benefits of the
      collective good. A common-enemy effect is instead systematically predicted for
      charity goods, where cooperators are excluded from the benefits of the collective
      good. These effects are maintained for congestible club goods and for congestible
      charity goods. As the degree to which a collective good is excludable can be
      meaningfully compared across different instances of cooperation, these
      contrasting predictions for public good, charity goods and club goods yield
      testable hypotheses for the common-enemy hypothesis of by-product mutualism.

PMID- 30296446
TI  - Building matrix population models when individuals are non-identifiable.
AB  - Matrix Population Models (MPM) are among the most widely used tools in ecology
      and evolution. These models consider the life cycle of an individual as composed
      by states to construct a matrix containing the likelihood of transitions between
      these states as well as sexual and/or asexual per-capita offspring contributions.
      When individuals are identifiable one can parametrize an MPM based on survival
      and fertility data and average development times for every state, but some of
      this information is absent or incomplete for non-cohort data, or for cohort data
      when individuals are not identifiable. Here we introduce a simple procedure for
      the parameterization of an MPM that can be used with cohort data when individuals
      are non-identifiable; among other aspects our procedure is a novelty in that it
      does not require information on stage development (or stage residence) times,
      which current procedures require to be estimated externally, and it is a frequent
      source of error. We exemplify the procedure with a laboratory cohort dataset from
      Eratyrus mucronatus (Reduviidae, Triatominae). We also show that even if
      individuals are identifiable and the duration of each stage is externally
      estimated with no error, our procedure is simpler to use and yields the same MPM
      parameter estimates.

PMID- 30296447
TI  - PBMDR: A particle swarm optimization-based multifactor dimensionality reduction
      for the detection of multilocus interactions.
AB  - Studies on multilocus interactions have mainly investigated the associations
      between genetic variations from the related genes and histopathological tumor
      characteristics in patients. However, currently, the identification and
      characterization of susceptibility genes for complex diseases remain a great
      challenge for geneticists. In this study, a particle swarm optimization (PSO)
      based multifactor dimensionality reduction (MDR) approach was proposed, denoted
      by PBMDR. MDR was used to detect multilocus interactions based on the PSO
      algorithm. A test data set was simulated from the genotype frequencies of 26 SNPs
      from eight breast-cancer-related gene. In simulated disease models, we
      demonstrated that PBMDR outperforms existing global optimization algorithms in
      terms of its ability to explore and power to detect specific SNP-genotype
      combinations. In addition, the PBMDR algorithm was compared with other
      algorithms, including PSO and chaotic PSOs, and the results revealed that the
      PBMDR algorithm yielded higher accuracy and chi-square values than other
      algorithms did.

PMID- 30296448
TI  - Mathematical modeling of bone marrow - peripheral blood dynamics in the disease
      state based on current emerging paradigms, part II.
AB  - The cancer stem cell hypothesis has gained currency in recent times but concerns
      remain about its scientific foundations because of significant gaps that exist
      between research findings and comprehensive knowledge about cancer stem cells
      (CSCs). In this light, a mathematical model that considers hematopoietic dynamics
      in the diseased state of the bone marrow and peripheral blood is proposed and
      used to address findings about CSCs. The ensuing model, resulting from a
      modification and refinement of a recent model, develops out of the position that
      mathematical models of CSC development, that are few at this time, are needed to
      provide insightful underpinnings for biomedical findings about CSCs as the CSC
      idea gains traction. Accordingly, the mathematical challenges brought on by the
      model that mirror general challenges in dealing with nonlinear phenomena are
      discussed and placed in context. The proposed model describes the logical
      occurrence of discrete time delays, that by themselves present mathematical
      challenges, in the evolving cell populations under consideration. Under the
      challenging circumstances, the steady state properties of the model system of
      delay differential equations are obtained, analyzed, and the resulting
      mathematical predictions arising therefrom are interpreted and placed within the
      framework of findings regarding CSCs. Simulations of the model are carried out by
      considering various parameter scenarios that reflect different experimental
      situations involving disease evolution in human hosts. Model analyses and
      simulations suggest that the emergence of the cancer stem cell population
      alongside other malignant cells engenders higher dimensions of complexity in the
      evolution of malignancy in the bone marrow and peripheral blood at the expense of
      healthy hematopoietic development. The model predicts the evolution of an
      aberrant environment in which the malignant population particularly in the bone
      marrow shows tendencies of reaching an uncontrollable equilibrium state.
      Essentially, the model shows that a structural relationship exists between CSCs
      and non-stem malignant cells that confers on CSCs the role of temporally
      enhancing and stimulating the expansion of non-stem malignant cells while also
      benefitting from increases in their own population and these CSCs may be the main
      protagonists that drive the ultimate evolution of the uncontrollable equilibrium
      state of such malignant cells and these may have implications for treatment.

PMID- 30296449
TI  - The seismic wave motion camouflage of large carnivorous dinosaurs.
AB  - Living elephants produce seismic waves during vocalizations and locomotion that
      are potentially detectable at large distances. In the Mesozoic world, seismic
      waves were probably a very relevant source of information about the behavior of
      large dinosaurs. In this work, we study the relationship between foot shape and
      the directivity pattern of seismic waves generated during locomotion. For
      enlarged foot morphologies (based on a morphological index) of theropod
      dinosaurs, there is a marked effect of seismic wave directivity at 20 m. This
      effect is not important in the foot morphologies of other dinosaurs, including
      the foot shapes of herbivores and theropods such as therizinosaurids. This
      directivity produces a lower intensity in the forward direction that would
      slightly reduce the probability of detection of an ambush predator. Even more
      relevant is the fact that during the approach of a predator, the intensity of
      seismic waves detected by potential prey remains constant in the mentioned
      distance range. This effect hides the predator's approach, and we call this
      "seismic wave camouflage". We also discuss the potential relationship of this
      effect with enlarged fossil footprints assigned to metatarsal support.

PMID- 30296450
TI  - Thresholds in the resilience of modular social networks to invasion by defectors.
AB  - Cooperative interactions constitute the backbone of many biological and social
      systems. Since cooperation is prone to exploitation, these systems must
      incorporate mechanisms that prevent the spreading of defective behaviors. One
      such mechanism is modularity, i.e., the tendency of a social network to be
      organized in modules, where individuals within a module tend to interact strongly
      among themselves while avoiding interacting with individuals from other modules.
      This structure allows cooperation to prevail by having modules of cooperative
      individuals with a limited exposure to defectors. To address the rate and shape
      of the effect of modularity on the resilience of cooperation, here we study a
      variant of the Prisoner's Dilemma on modular networks. Our simulations reveal a
      sharp transition between a resilient and a vulnerable regime as modularity
      exceeds a critical threshold. By using a simplified mathematical model, we show
      that the observed threshold is equivalent to the epidemic threshold found in a
      certain class of SIR models. This allows us to derive an explicit condition under
      which a cooperative society is expected to be resilient to invasive defectors.

PMID- 30296451
TI  - Nutritional supplementation in the treatment of glaucoma: a systematic review.
AB  - Current treatment strategies for glaucoma are limited to halting disease
      progression and do not restore lost visual function. Intraocular pressure (IOP)
      is the main risk factor for glaucoma and IOP-lowering treatment remains the
      mainstay of glaucoma treatment, but even successful IOP reduction does not stop
      the progression of glaucoma in all patients. We review the literature to
      determine whether nutritional interventions intended to prevent or delay the
      progression of glaucoma can prove to be a valuable addition to the mainstay of
      glaucoma therapy. A total of 33 intervention trials were included in this review,
      including 21 randomized controlled trials. These suggest that flavonoids exert a
      beneficial effect in glaucoma, particularly in terms of improving ocular blood
      flow and potentially slowing progression of visual field loss. Additionally,
      supplements containing forskolin have consistently demonstrated the capacity to
      significantly reduce IOP beyond the levels achieved with traditional therapy
      alone; however, despite the strong theoretical rationale and initial clinical
      evidence for the beneficial effect of dietary supplementation as an adjunct
      therapy for glaucoma, the evidence is not conclusive. More and better quality
      research is required to evaluate the role of nutritional supplementation in
      glaucoma.

PMID- 30296452
TI  - Conserved epitopes in variants of amastin protein of Trypanosoma cruzi for
      vaccine design: A bioinformatics approach.
AB  - Chagas disease caused by protozoan parasite Trypanosoma cruzi is endemic disease
      in South and Central American countries but due to migrating human populations it
      has shown emergence in Europe, North America and Australia. With only two drugs,
      benznidazole and nifurtimox for its treatment there is need for newer therapies.
      In the current study, we have tried to analyse the potential of amastin, a major
      surface protein as a vaccine target using bioinformatics tools. Using 282
      variants of this protein available in NCBI protein database we have found out
      five conserved potential Tc cell and two TH cell epitopes. These epitopes are
      conserved in more than 90% of the cohort of sequences used in the study. The
      epitopes showed binding to the peptide binding cleft of HLA-A02 and HLA-DR
      molecules. With coverage of pan world populations and being non-toxic and non
      allergic these epitopes could be used for future vaccine applications.

PMID- 30296453
TI  - Effects of resistance training on neuromuscular parameters in elderly with type 2
      diabetes mellitus: A randomized clinical trial.
AB  - This study is a randomized controlled clinical trial that verified the resistance
      training efficacy on neuromuscular parameters, with muscle quality as primary
      outcome. Forty-four elderly with diabetes type 2 (69.7 +/- 6.9 years; 26 men)
      were randomly allocated to a 12-weeks resistance training group (RTG, 3 times a
      week), or an active control group with stretching classes (CG, once a week).
      Primary and secondary outcomes were assessed at baseline and after 12 weeks, as
      follow: quadriceps muscle thickness and rectus femoris muscle quality, maximal
      knee extension strength, rapid strength, functional performance, visceral adipose
      tissue, glycemic control, lipid profile and quality of life. Generalized
      estimating equations were used to analyses based on intention-to-treat and per
      protocol approaches, which showed the same results. Among all outcomes measured
      there were improvements in the knee extension strength (P < 0.001) and quadriceps
      muscle thickness (P < 0.001) for RTG. The muscle quality did not improve for both
      groups (P = 0.98). For the secondary outcomes there were no improvements for
      functional performance, rapid strength, glycemic control, quality of life,
      visceral adipose tissue and lipid profile in both groups, with exception of
      triglyceride level reduction for RTG (P = 0.04).The resistance training program
      is an efficacious strategy for improve the neuromuscular health in elderly with
      T2DM, considering increases in lower limb strength and muscle mass, but the same
      was not found for muscle quality, rapid strength, functional performance and
      quality of life. Furthermore, the training program did not induce significant
      reduction in glycated hemoglobin values of patients who already had suitable
      glycemic control.

PMID- 30296454
TI  - Associations between gait coordination, variability and motor cortex inhibition
      in young and older adults.
AB  - Interlimb coordination and gait performance diminish with age, posing a risk for
      gait-related injuries. Further, levels of inhibition within the motor cortex are
      significantly associated with coordination of the upper extremities in healthy
      aging, however, it is unknown if this same association exists for lower extremity
      control. To investigate the relationship between gait coordination and cortical
      inhibition we measured gait coordination via the phase coordination index and
      motor cortex inhibition via the cortical silent period in 14 young and 15 older
      adults. Gait coordination was reduced in older adults while walking at their self
      selected pace, as was cortical inhibition, solely in the non-dominant motor
      cortex. Furthermore, young adults were better able to maintain lower extremity
      coordination and variability with reduced cortical inhibition, whereas older
      adults with increased cortical inhibition demonstrated better walking
      performance. These findings suggest a fundamental shift in the relationship
      between motor cortex inhibition and lower extremity control with age, similar to
      previous work demonstrating an age-related difference in the association between
      motor cortex inhibition with bimanual control.

PMID- 30296455
TI  - Cunaniol-elicited seizures: Behavior characterization and electroencephalographic
      analyses.
AB  - This study aimed at describing the characteristics and properties of seizures
      induced by cunaniol, a polyacetylenic alcohol isolated from the Clibadium genus,
      which is ubiquitous in the Amazon biodiversity and its potential use as a
      convulsant model. Wistar rat behavior was assessed upon cunaniol administration
      and animals were evaluated for neural activity through electroencephalographic
      records whereby epidural electrodes were positioned over the motor cortex under
      cunaniol-elicited seizures and seizure's control using three anticonvulsant
      agents, namely phenytoin, phenobarbital and diazepam. Cunaniol-induced seizures
      displayed a cyclic development of electrocorticographic seizures, presenting
      interictal-like spike and ictal period, which correlates to the behavioral
      observations and is in line with acute seizures induced by pentylenetetrazole.
      Cunaniol-elicited seizures were intractable by phenytoin treatment and controlled
      under the GABAergic activities of phenobarbital and diazepam. The results
      indicate that the cunaniol-induced changes show characteristics of seizure
      activity, making this plant compound a suitable animal convulsant model for
      seizure-related studies that could be used to assist in the development of novel
      anticonvulsant agents.

PMID- 30296456
TI  - Metabolic dynamics of human Sertoli cells are differentially modulated by
      physiological and pharmacological concentrations of GLP-1.
AB  - Obesity incidence has pandemic proportions and is expected to increase even
      further. Glucagon-like peptide-1 (GLP-1) based therapies are well-established
      pharmacological resources for obesity treatment. GLP-1 regulates energy and
      glucose homeostasis, which are also crucial for spermatogenesis. Herein, we
      studied the GLP-1 effects in human Sertoli cells (hSCs) metabolism and
      mitochondrial function. hSCs were cultured in absence or exposed to increasing
      doses of GLP-1 mimicking physiological post-prandial (0.01 nM) levels or
      equivalent to pharmacological levels (1 and 100 nM) used for obesity treatment.
      We identified GLP-1 receptor in hSCs. Consumption/production of extracellular
      metabolites were assessed, as well as protein levels or activities of glycolysis
      related enzymes and transporters. Mitochondrial membrane potential and oxidative
      damage were evaluated. Glucose consumption decreased, while lactate production
      increased in hSCs exposed to 0.01 and 1 nM GLP-1. Though lactate dehydrogenase
      (LDH) protein decreased after exposure to 100 nM GLP-1 its activity increased in
      hSCs exposed to the same concentration of GLP-1. Mitochondrial membrane potential
      decreased in hSCs exposed to 100 nM of GLP-1, while formation of carbonyl groups
      was decreased in those cells. Those effects were followed by an increase in p
      mammalian target of rapamycin (mTOR) Ser(2448). Overall, the lowest
      concentrations of GLP-1 increased the efficiency of glucose conversion to
      lactate, while GLP-1 concentration of 100 nM induces mTOR phosphorylation,
      decreases mitochondrial membrane potential and oxidative damage. GLP-1 regulates
      testicular energy homeostasis and pharmacological use of GLP-1 analogues could be
      valuable to counteract the negative impact of obesity in male reproductive
      function.

PMID- 30296457
TI  - Primary resistance mechanism of the canine distemper virus fusion protein against
      a small-molecule membrane fusion inhibitor.
AB  - Morbilliviruses (e.g. measles virus [MeV] or canine distemper virus [CDV]) employ
      the attachment (H) and fusion (F) envelope glycoproteins for cell entry. H
      protein engagement to a cognate receptor eventually leads to F-triggering. Upon
      activation, F proteins transit from a prefusion to a postfusion conformation; a
      refolding process that is associated with membrane merging. Small-molecule
      morbilliviral fusion inhibitors such as the compound 3G (a chemical analog in the
      AS-48 class) were previously generated and mechanistic studies revealed a
      stabilizing effect on morbilliviral prefusion F trimers. Here, we aimed at
      designing 3G-resistant CDV F mutants by introducing single cysteine residues at
      hydrophobic core positions of the helical stalk region. Covalently-linked F
      dimers were generated, which highlighted substantial conformational flexibility
      within the stalk to achieve those irregular F conformations. Our findings
      demonstrate that "top-stalk" CDV F cysteine mutants (F-V571C and F-L575C)
      remained functional and gained resistance to 3G. Conversely, although not all
      "bottom-stalk" F cysteine variants preserved proper bioactivity, those that
      remained functional exhibited 3G-sensitivity. According to the recently
      determined prefusion MeV F trimer/AS-48 co-crystal structure, CDV residues F-V571
      and F-L575 may directly interact with 3G. A combination of conformation-specific
      anti-F antibodies and low-resolution electron microscopy structural analyses
      confirmed that 3G lost its stabilizing effect on "top-stalk" F cysteine mutants
      thus suggesting a primary resistance mechanism. Overall, our data suggest that
      the fusion inhibitor 3G stabilizes prefusion CDV F trimers by docking at the top
      of the stalk domain.

PMID- 30296458
TI  - Identification and full-genome characterization of novel circoviruses in masked
      palm civets (Paguma larvata).
AB  - The family Circoviridae comprises a large group of small, circular, single
      stranded DNA viruses and is classified into two genera: Circovirus and
      Cyclovirus. They have marked genetic diversity and a broad host range. In this
      study, three novel circovirus genomes were identified from wild-caught masked
      palm civets (Paguma larvata) in Japan and classified as a new species within the
      genus Circovirus based on the demarcation criteria of the International Committee
      on the Taxonomy of Viruses. Of note, the presence of two predicted introns at the
      5'-terminus of the rep gene was suggested in the Paguma larvata circovirus
      genomes.

PMID- 30296459
TI  - Na+, K+-ATPase inhibition causes hyperactivity and impulsivity in mice via
      dopamine D2 receptor-mediated mechanism.
AB  - Hyperactivity and impulsivity are common symptoms in several psychiatric
      disorders. Although dysfunction of Na+, K+-ATPase has been reported to be
      associated with the psychiatric disorders, it is not clear whether inhibition of
      Na+, K+-ATPase causes behavioral effects, including hyperactivity and
      impulsivity, in mice. Here, we evaluated the effect of intracerebroventricular
      (icv) injection of ouabain, an inhibitor of Na+, K+-ATPase, on hyperactivity and
      impulsivity in mice. At seven days after icv injection, ouabain-injected mice
      displayed the increase in the distance traveled in the open field arena in the
      open field test and the increase in the number of head-dipping behavior in the
      cliff avoidance test. Chlorpromazine or haloperidol, typical antipsychotics,
      reduced the hyperactivity and impulsivity in ouabain-injected mice. On the other
      hand, neither lithium carbonate nor valproate, established mood-stabilizing
      drugs, improved hyperactivity and impulsivity in our mouse model. Furthermore,
      ouabain-injected mice exhibited the increase in the number of c-fos-positive
      cells in the nucleus accumbens and the prefrontal cortex but not in the ventral
      tegmental area, which was reduced by haloperidol. These results suggest that the
      dysfunction of Na+, K+-ATPase causes hyperactivity and impulsivity via
      hyperactivation of dopamine D2 receptor-mediated signaling pathway, causing
      disturbed neuronal circuits in mice.

PMID- 30296460
TI  - AIEgen based drug delivery systems for cancer therapy.
AB  - Fluorescent drug delivery systems provide a means to track drug release, trace
      processes of translocation, monitor excretion of anticancer agents and predict
      therapeutic responses. Traditional fluorescent dye-labeled drug delivery systems
      often suffer from notorious aggregation-caused quenching (ACQ) with greatly
      impeded imaging performance. The emerging fluorogens with aggregation-induced
      emission characteristics (AIEgens) have provided an elegant alternative to tackle
      this challenge. Recently, fluorescent drug delivery systems based on AIEgens
      which combine fluorescence imaging and drug delivery have been extensively
      studied for the development of theranostic nanomedicine. In this review, we
      summarize the recent development of fluorescent drug delivery systems using
      AIEgens as the signal reporter. This review is organized according to the drug
      delivery systems, which include: (1) AIEgens as the drug delivery carrier; (2)
      AIE polymer as the drug delivery carrier; (3) Organic-inorganic AIE nanocarrier
      for drug delivery; (4) Supramolecular AIE system for drug delivery. Through
      illustration of their design principles and application examples, we hope to
      stimulate more interest in the design of more advanced fluorescent drug delivery
      systems based on AIEgens for cancer therapy.

PMID- 30296462
TI  - Preconception risk of gestational diabetes: Development of a prediction model in
      nulliparous Australian women.
AB  - AIM: To develop a prediction model for preconception identification of women at
      risk of gestational diabetes mellitus (GDM). METHODS: Data from a prospective
      cohort, the Australian Longitudinal Study on Women's Health, were used.
      Nulliparous women aged 18-23 who reported a pregnancy up to age 37-42 were
      included. Preconception predictors of GDM during a first pregnancy were selected
      using logistic regression. Regression coefficients were multiplied by a shrinkage
      factor estimated with bootstrapping to improve prediction in external
      populations. RESULTS: Among 6504 women, 314 (4.8%) developed GDM during their
      first pregnancy. The final prediction model included age at menarche, proposed
      age at future first pregnancy, ethnicity, body mass index, diet, physical
      activity, polycystic ovary syndrome, and family histories of type 1 or 2 diabetes
      and GDM. The model showed good discriminative ability with a C-statistic of 0.79
      (95% CI 0.76, 0.83) after internal validation. More than half of the women (58%)
      were classified to be at risk of GDM (>2% predicted risk), with corresponding
      sensitivity and specificity values of 91% and 43%. CONCLUSIONS: Nulliparous women
      at risk of GDM in a future first pregnancy can be accurately identified based on
      preconception lifestyle and health-related characteristics. Further studies are
      needed to test our model in other populations.

PMID- 30296463
TI  - Bacopa monnieri alleviates paraquat induced toxicity in Drosophila by inhibiting
      jnk mediated apoptosis through improved mitochondrial function and redox
      stabilization.
AB  - Paraquat (PQ) is an organic chemical compound and a member of redox active family
      of heterocycles. In spite of its high toxicities, it is used as one of the potent
      herbicide throughout the world. Though its toxic manifestations are observed in
      different organs, its principal toxic effect is manifested in the brain leading
      to the development of Parkinsonian symptoms. PQ exposure adversely affects
      dopaminergic (DA-ergic) neuron-rich region in the substantia nigra pars compacta
      (SNPC) of brain in the animal models of Parkinson's disease (PD), thereby
      mimicking PD like symptoms. Currently, lack of a potential drug to counter the
      toxic effect of PQ makes the management difficult. Bacopa monnieri extract (BME)
      has been shown to have promising effect against neurodegenerative disorders.
      Therefore, the present study evaluated the role of BME against PQ induced
      toxicity in Drosophila model of PD, the results of which are reproducible in
      higher animal models including human subjects. Here, we showed that BME treatment
      attenuates acute PQ induced toxicity in Drosophila by decreasing mortality and
      improving climbing ability. BME functions by optimizing redox equilibrium,
      mitochondrial function and depreciating apoptosis level. The underlying
      mechanisms were attributed to optimization of active JNK and cleaved Caspase-3
      activity along with transcriptional stabilization of the genes regulating
      oxidative stress and apoptosis (jnk, caspase-3, damb and nrf-2). These results
      showed therapeutic efficacy of BME against PQ toxicity in the brain. Our results
      pave the way for further detailed analysis of BME to combat the development of
      Parkinson's like symptoms following exposure to PQ toxicity in the brain of
      higher animal models.

PMID- 30296461
TI  - Reducing inflammation through delivery of lentivirus encoding for anti
      inflammatory cytokines attenuates neuropathic pain after spinal cord injury.
AB  - Recently, many clinical trials have challenged the efficacy of current
      therapeutics for neuropathic pain after spinal cord injury (SCI) due to their
      life-threatening side-effects including addictions. Growing evidence suggests
      that persistent inflammatory responses after primary SCI lead to an imbalance
      between anti-inflammation and pro-inflammation, resulting in pathogenesis and
      maintenance of neuropathic pain. Conversely, a variety of data suggest that
      inflammation contributes to regeneration. Herein, we investigated long-term local
      immunomodulation using anti-inflammatory cytokine IL-10 or IL-4-encoding
      lentivirus delivered from multichannel bridges. Multichannel bridges provide
      guidance for axonal outgrowth and act as delivery vehicles. Anti-inflammatory
      cytokines were hypothesized to modulate the pro-nociceptive inflammatory niche
      and promote axonal regeneration, leading to neuropathic pain attenuation. Gene
      expression analyses demonstrated that IL-10 and IL-4 decreased pro-nociceptive
      genes expression versus control. Moreover, these factors resulted in an increased
      number of pro-regenerative macrophages and restoration of normal nociceptors
      expression pattern. Furthermore, the combination of bridges with anti
      inflammatory cytokines significantly alleviated both mechanical and thermal
      hypersensitivity relative to control and promoted axonal regeneration.
      Collectively, these studies highlight that immunomodulatory strategies target
      multiple barriers to decrease secondary inflammation and attenuate neuropathic
      pain after SCI.

PMID- 30296464
TI  - The complete mitochondrial genome of Budorcas taxicolor tibetana (Artiodactyla:
      Bovidae) and comparison with other Caprinae species: Insight into the phylogeny
      of the genus Budorcas.
AB  - Takin (Budorcas taxicolor) is one of the most endangered species. However, the
      taxonomy of takin is still in dispute. Here, the complete mitochondrial genome of
      Budorcas taxicolor tibetana was reported for the first time, which featured a
      typical circular molecule of 16,665 bp in length, including 13 PCGs, 22 tRNAs,
      two rRNAs, and one control region. A + T content was higher than G + C content.
      All of the genes were encoded on the heavy strand, except for eight tRNAs and ND6
      gene. The OL region was 49 bp in length and highly conserved in the synthesis and
      stem-loop regions, and all of the substitutions and indels were found only in the
      loop structure. Three types of tandem repeat units, six pairs of hairpin loop
      structure (TACAT, ATGTA) and six CSBs were predicted in the control region. Our
      results clearly revealed the systematic status of Budorcas species, and the
      phylogenetic analyses indicated that Budorcas was closer to Capra and Pseudois,
      rather than to Ovis, which should be merged into the subfamily of Caprinae.

PMID- 30296465
TI  - MiR-650 regulates the proliferation, migration and invasion of human oral cancer
      by targeting growth factor independent 1 (Gfi1).
AB  - Oral cancer being one of the lethal cancers is generally detected at advanced
      stages and causes significant mortality world over. The unavailability of the
      reliable biomarkers and therapeutic targets/agents forms a bottleneck in the
      treatment of oral cancer. MicroRNAs are considered of immense therapeutic
      potential for the treatment of cancer. Consistently, in this study the role and
      therapeutic potential of miR-650 was explored in oral cancer. The analysis of miR
      650 expression by qRT-PCR revealed significant (p < 0.05) upregulation of miR-650
      in oral cancer cell lines. Cell cycle analysis by flow cytometery revealed that
      suppression of miR-650 significantly (p < 0.05) inhibits the proliferation of the
      SCC-25 cells by prompting Sub-G1 cell cycle arrest. Further, miR-650 suppression
      also inhibited the migration and invasion of the SCC-25 oral cancer cells as
      revealed by transwell assays. TargetScan analysis showed that miR-650 targets
      Growth factor independent 1 (Gfi1). Moreover, the results of western blot
      analysis showed that miR-650 suppression inhibits the expression of Gfi1.
      Interestingly, suppression of Gfi1 exhibited similar effects on cell
      proliferation, migration and invasion of the oral cancer cells as that of miR-650
      suppression. Nonetheless, miR-650 promoted the proliferation, migration and
      invasion of the SCC-25 cells by upregulating the expression of Gfi1. Moreover,
      overexpression of miR-650 could not rescue the effects of Gfi1 silencing on SCC
      25 oral cancer cells. Conversely, overexpression of Gfi1 could rescue the effects
      of miR-650 inhibition on SCC-25 cell proliferation, migration and invasion.
      Additionally, miR-650 suppression could also inhibit the xenografted tumor growth
      in vivo by inhibiting the expression of Gfi1. Taken together, miR-650 may prove
      to be an important therapeutic target for the management of oral cancers.

PMID- 30296466
TI  - A systematic review of in vitro cytokine production in eating disorders.
AB  - BACKGROUND: Eating disorders (EDs) have been associated with alterations in
      cytokine concentrations and production. This review examines whether in vitro
      cytokine production (i) is altered in people with EDs compared to healthy
      participants; and (ii) changes in response to treatment? METHODS: Using PRISMA
      guidelines, we systematically reviewed articles reporting group comparisons or
      longitudinal assessments of spontaneous and/or stimulated cytokine production in
      vitro in people with EDs. RESULTS: Twelve studies were included. Cross-sectional
      results were mixed in anorexia nervosa. Only one study measured cytokine
      production in bulimia nervosa. Two longitudinal studies showed that daily yoghurt
      consumption increases phytohemagglutinin-stimulated interferon-gamma production
      in anorexia nervosa. CONCLUSION: The mixed results could be accounted for by
      variations in experimental design. Our findings suggest that cytokine production
      could possibly be modulated through dietary interventions. However, due to the
      methodological heterogeneity and shortcomings of the included studies, it seems
      unreasonable to draw further conclusions.

PMID- 30296467
TI  - Neutral is negative enough-Peer victimization influences cardiac, facial-muscular
      and experiential reactions to both negative evaluative and neutral social
      stimuli.
AB  - Physiological stress responses vary as a function of adverse childhood
      experiences. However, previous studies concentrate on familial sources of
      childhood adversity. Potential long-term effects of peer victimization on
      physiology and affective responses are less known. This study examined cardiac,
      facial-muscular, and experiential responses to social evaluative stimuli in
      ninety-four healthy subjects with various degrees of experienced peer
      victimization. In a social conditioning task, peer victimization was associated
      with similarly attenuated cardiac and facial-muscular responses to negative and
      neutral stimuli, while differentiated physiological responses to negative and
      neutral stimuli were found in subjects without peer victimization. Overall,
      increased ratings of arousal, valence and disapproval for negative compared to
      neutral stimuli were found. Contrary to the physiological response, peer
      victimization was associated with more negative ratings of negative stimuli one
      month after acquisition. The results suggest that the physiological and
      experiential reactivity towards both negative and neutral social stimuli is
      affected by the experience of peer victimization. Peer victimization causes
      generalized autonomic dysregulation and memory recall biases during social
      learning impeding adequate response preparation to social stressors.

PMID- 30296468
TI  - Use and handling safety of Mini-Spike 2(r) chemo and puresite for safe
      chemotherapy compounding in a hospital pharmacy.
AB  - We wanted to evaluate the impact of Mini-Spike 2(r) Chemo + Puresite (MSCP) use
      on contamination surface levels, professionals' satisfaction and compounding time
      at pharmacy compared with PhasealTM. Presence of cyclophosphamide (CYP) and 5
      fluorouracil (5FU) was evaluated at three sampling times: baseline; after a
      decontamination procedure and six months after MSCP use for CYP and 5FU
      compounding. Testing was carried out using an independent laboratory and wipe
      testing kit. To test compounding time, four different nurses followed the same
      compounding protocol with each device. We also developed a questionnaire to
      obtain feedback from the nurses. We did not find statistically significant
      differences in the median contamination surface levels between basal and final
      sampling time, CYP (0.140; 95% CI -1.135, 1.601), 5FU (-0.506; 95% CI -1.756,
      0.287). We observed a difference of 10 s on compounding times between the two
      devices tested (p < 0.001) favoring MSCP. Finally, eight nurses answered the
      survey, with the best valued aspect as the aspiration/injection flow and
      resistance, and the worst value the comfort using Puresite and valve connection.
      MSCP maintains low surface contamination levels in our setting assuring
      compounding time standards. Satisfaction survey let us know which were the major
      advantages and disadvantages of the device.

PMID- 30296469
TI  - Effect of a binge-like dosing regimen of methamphetamine on dopamine levels and
      tyrosine hydroxylase expressing neurons in the rat brain.
AB  - Methamphetamine, an amphetamine derivative, is a powerful psychomotor stimulant
      and commonly used drug of abuse. This study examined the effect of binge-like
      methamphetamine (MA) dosing (4 * 4 mg/kg, s.c., 2 h apart) on regional dopamine
      and dopaminergic metabolite levels in rat brain at a range of early time points
      after final dose (2-48 h). Body temperature was elevated when measured 2 h after
      the last dose. MA increased dopamine levels in the frontal cortex 2 and 24 h
      after the last dose. The dopamine level was also increased in the amygdala at 24
      h. No change was observed in the striatum at any time point, but levels of the
      dopamine metabolite DOPAC were markedly reduced at 24 and 48 h. Tyrosine
      hydroxylase expression is induced downstream of dopamine activity, and it is the
      rate limiting enzyme in dopamine synthesis. The effect of MA binge-like dosing on
      the volume of tyrosine hydroxylase containing cell bodies and the area fraction
      of tyrosine hydroxylase containing fibres was also assessed. MA increased the
      area fraction of tyrosine hydroxylase fibres in the frontal cortex and reduced
      the volume of tyrosine hydroxylase containing cell bodies 2 h after last dose in
      the ventral tegmental area and the substantia nigra. An increase in cell body
      volume in the substantia nigra was observed 48 h after treatment. These findings
      collectively highlight the importance of the dopaminergic system in
      methamphetamine induced effects, identify the frontal cortex, amygdala and
      striatum as key regions that undergo early changes in response to binge-like
      methamphetamine dosing and provide evidence of time-dependent effects on the cell
      bodies and fibres of tyrosine hydroxylase expressing neurons.

PMID- 30296470
TI  - Protective role of Apelin-13 on amyloid beta25-35-induced memory deficit;
      Involvement of autophagy and apoptosis process.
AB  - Alzheimer's disease (AD) by progressive neurodegenerative pattern is associated
      with autophagy stress which is suggested as a potential cause of amyloid beta
      (Abeta) aggregation and neural loss. Apelin-13, a neuropeptide with modulatory
      effect on autophagy, has been shown the beneficial effects on neural cell
      injuries. We investigated the effect of Apelin-13 on Abeta-induced memory deficit
      as well as autophagy and apoptosis processes. We performed bilateral intra-CA1
      injection of Abeta25-35 alone or in combination with Apelin-13. Spatial reference
      and working memory was evaluated using the Morris water maze (MWM) and Y-maze
      tests. Hippocampus was harvested on 2, 5, 10 and 21 days after Abeta injection.
      The light chain 3 (LC3II/I) ratio, histone deacetylase 6 (HDAC6) level, Caspase-3
      cleavage, and mTOR phosphorylation were assessed using western blot technique.
      Intra-CA1 injection of Abeta caused impairment of working and spatial memory. We
      observed higher LC3II/I ratio, cleaved caspase-3 and lower HDAC6, and p-mTOR/mTOR
      ratio in Abeta-treated animals. Apelin-13 provided significant protection against
      the destructive effects of Abeta on working and spatial memory. Apelin-13
      prevented the increase of LC3II/I ratio and cleaved caspase-3 on days 10 and 21
      after injection of Abeta. It also limited the Abeta-induced reduction in HDAC6
      expression. This implies that Apelin-13 has suppressed both autophagy and
      apoptosis. Our findings suggested that the neuroprotection of Apelin-13 may be in
      part related to autophagy and apoptosis inhibition via the mTOR signaling
      pathway. Apelin-13 may be a promising approach to improve memory impairment and
      potentially pave the way for new therapeutic plans in AD.

PMID- 30296471
TI  - A simple and highly efficient method for gene silencing in Escherichia coli.
AB  - Here we present a simple and rapidly achievable protocol for gene silencing in
      Escherichia coli (E. coli). In this procedure, antisense RNA (asRNA) of 400
      nucleotides (nt) length and absolute complementarity to the target is produced by
      an expression plasmid. The designed asRNA should ideally cover at least the -10
      site of the promoter and the Shine-Dalgarno sequence, and additional 300-bp of
      the following open reading frame of the target gene. We show that the
      transcription process of the target is not affected at all, whereas the
      translation process is impaired. Based on high constitutive expression of asRNA
      we were able to extend the silencing effect to knock-out levels. By inducible
      expression, we show that also the modulation is possible. This technique should
      be widely useful to study gene function in E. coli and other bacteria.

PMID- 30296472
TI  - Eating As Treatment (EAT): a stepped-wedge, randomised controlled trial of a
      health behaviour change intervention provided by dietitians to improve nutrition
      in patients with head and neck cancer undergoing radiotherapy (TROG 12.03).
AB  - PURPOSE: Malnutrition in head and neck cancer (HNC) treatment is common and
      associated with poorer morbidity and mortality outcomes. This trial aimed to
      improve nutritional status during radiotherapy using a novel method of training
      dietitians to deliver psychological techniques to improve HNC patients'
      nutritional behaviours. METHODS AND MATERIALS: This trial used a stepped wedge
      randomised controlled design to assess the efficacy of Eating As Treatment (EAT).
      Based on Motivational Interviewing and Cognitive Behavioural Therapy, EAT was
      designed to be delivered by oncology dietitians and integrated into their
      clinical practice. During control steps, dietitians provided treatment as usual,
      before being trained in EAT and moving into the intervention phase. The training
      was principles based and sought to improve behaviour change skills rather than
      provide specific scripts. Patients recruited (151 controls, 156 intervention) to
      the trial were assessed at four time points (first and final week of
      Radiotherapy, four and twelve weeks post). The primary outcome was nutritional
      status at the end of RT as measured by the Patient Generated Subjective Global
      Assessment (PG-SGA). RESULTS: Patients who received the EAT intervention had
      significantly better scores on the primary outcome of nutritional status at the
      critical end of treatment time point (beta=-1.53 (-2.93 to -.13) p=.03).
      Intervention patients were also significantly more likely to: be assessed as well
      nourished at each time point; lose a smaller percentage of weight have fewer
      treatment interruptions; present lower depression scores; and report a higher
      quality of life. Although not statistically significant, those who received the
      intervention had fewer and shorter unplanned hospital admissions. CONCLUSIONS:
      This trial is the first of its kind to demonstrate the effectiveness of a
      psychological intervention to improve nutrition in HNC patients receiving
      radiotherapy. It provides a means to ameliorate malnutrition and the important
      related outcomes and consequently should be incorporated into standard care for
      patients receiving HNC radiotherapy.

PMID- 30296473
TI  - Patterns of care and outcome Radiation-Induced Soft Tissue Sarcomas.
AB  - More than half of all cancer patients receive radiotherapy. With the increasing
      number of long-term cancer survivors, there is a growing concern about the risk
      of radiation induced second malignant neoplasm. Sarcomas represent the most
      frequent type of cancer than can be induced by radiation exposure. We report the
      largest series of radiation-induced sarcomas (RIS). We demonstrate that a
      majority of RIS can be cured, provided they underwent well-planned surgery.

PMID- 30296474
TI  - Parvalbumin Loss Following Chronic Sub-Anesthetic NMDA Antagonist Treatment is
      Age-Dependent in the Hippocampus: Implications for Modeling NMDA Hypofunction.
AB  - A marked decrease in parvalbumin (PV), a calcium-binding protein specific to a
      subset of GABAergic neurons, is a consistent finding in postmortem schizophrenic
      brain tissue. This reduction is selective to PV and is regionally specific,
      occurring primarily in the prefrontal cortex and hippocampus (HPC) of patients.
      Rodent models of NMDA receptor hypofunction utilizing NMDA antagonist treatments 
      e.g. ketamine (KET) - show schizophrenia-like cognitive and behavioral
      impairments with parallel changes in PV. While decreased PV is considered a
      hallmark of neuropathology in schizophrenia, previous work elucidating the
      effects of KET administration on PV are contradictory, with findings suggesting
      decreased, increased, or no change in PV expression. Upon close examination of
      the procedures used across studies, there are two primary inconsistencies,
      including: (1) the age of animals used; and (2) the timeline of post-treatment
      tissue collection. To better understand whether these key differences impact
      observed PV changes, the present study investigated the impact of age and time of
      sacrifice on chronic KET-induced PV changes in the neocortex and HPC. Our
      findings suggest an effect of age, but not sacrifice timeline, on PV cell count
      following 14 days of sub-anesthetic KET treatment. We provide evidence that 1
      month-old rats exhibit a significant KET-induced HPC PV decrease, while adult
      rats show a modest increase in HPC PV following chronic KET. Taken together, we
      propose that PV is a dynamic marker, and that changes in cell counts - and their
      interpretation - following NDMA antagonist treatment should be considered in the
      context of age.

PMID- 30296476
TI  - Application of Sentinel Lymph Node Technique to Transvaginal Natural Orifices
      Transluminal Endoscopic Surgery in Endometrial Cancer.
AB  - STUDY OBJECTIVE: This report outlines our first experience of sentinel lymph node
      (SLN) mapping in the natural orifices transluminal endoscopic surgery (NOTES)
      technique, which is the combination of the least invasive surgical approach and
      the least invasive way of assessing lymph node status. DESIGN: Descriptive study
      (Canadian Task Force classification III). SETTING: Tertiary referral and
      educational center. PATIENTS: Four patients with endometrial cancer clinical
      stage 1. INTERVENTIONS: NOTES with SLN mapping using an indocyanine green-based
      near-infrared fluorescence imaging technique. MEASUREMENTS AND MAIN RESULTS: The
      average operative time was 182.75 minutes (standard deviation, 34.5). Mean
      estimated blood loss was 67.5 mL (standard deviation, 39.4). All patients had
      surgical staging of International Federation of Gynecology and Obstetrics stage
      IA (pT1aN0). The overall detection rate and bilateral detection rate were 100%
      (4/4). All procedures were successfully completed without complication or
      conversion to conventional laparoscopy. CONCLUSION: In our preliminary
      experience, SLN mapping in NOTES surgery appears to be feasible and safe. It can
      be considered as an alternative method to reduce morbidity from radical
      lymphadenectomy and provide the benefits from the NOTES technique. However,
      studies in a larger population are necessary.

PMID- 30296475
TI  - Efficacy of a Fibrin Sealant (Tissucol Duo) for the Preventionof Lymphocele after
      Laparoscopic Pelvic Lymphadenectomy:A Randomized Controlled Trial.
AB  - STUDY OBJECTIVE: To assess the efficacy of Tissucol Duo (Baxter AG, Vienna,
      Austria) fibrin sealant in decreasing the incidence of lymphocele (LC) after
      pelvic laparoscopic lymph node dissection using harmonic shears. DESIGN:
      Randomized controlled trial (Canadian Task Force classification level I).
      SETTING: Tertiary referral and educational center. PATIENTS: Seventy-four
      patients randomized to the use of sealant per hemipelvis. INTERVENTION: Fibrin
      sealant. MEASUREMENTS AND MAIN RESULTS: After bilateral pelvic lymphadenectomy a
      fibrin sealant was used in 1 hemipelvis but not the other, applied in 41 patients
      (55.4%) to the left and 33 patients (44.6%) to the right hemipelvis. The primary
      outcome was the incidence of LC after surgery in symptomatic and asymptomatic
      patients. Imaging (ultrasound, computed tomography, and magnetic resonance) was
      performed to detect LC at 3, 6, and 12 months after surgery. Overall, 26 patients
      (35.1%) developed LC, and 4 were symptomatic (5.4%). Allowing patients to serve
      as their own treatment group and control, the hemipelvis treated with Tissucol
      Duo corresponding to the treatment group and that not treated to the control
      group, LCs were found in 17 (23%) and 14 (19%) cases, respectively, but the
      difference was not significant. The mean initial LC maximum diameter was 27.1 mm
      (standard deviaiotn, 35.2), and LCs tended to decrease in size during the first
      year to a mean of 8.7 mm. CONCLUSION: Application of Tissucol Duo fibrin sealant
      after laparoscopic pelvic lymphadenectomy using ultrasonic shears does not
      decrease the occurrence of symptomatic or asymptomatic LC.

PMID- 30296477
TI  - Role of calcium in adult onset polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in
      genes encoding the polycystin (PC) 1 and 2 proteins. The goal of this study was
      to determine the role of calcium in regulating cyst growth. Stromal interaction
      molecule 1 (STIM1) protein expression was 15-fold higher in PC1-null proximal
      tubule cells (PN) than in heterozygote (PH) controls and 2-fold higher in an
      inducible, PC1 knockout, mouse model of ADPKD compared to a non-cystic match
      control. IP3 receptor protein expression was also higher in the cystic mice.
      Knocking down STIM1 with siRNA reduced cyst growth and lowered cAMP levels in PN
      cells. Fura2 measurements of intracellular Ca2+ showed higher levels of
      intracellular Ca2+, SOCE and thaspigargin-stimulated ER Ca2+ release in PN vs. PH
      cells. There was a dramatic reduction in thapsigargin-stimulated release of ER
      Ca2+ following STIM1 silencing or application of 2-APB, consistent with altered
      ER Ca2+ movement; the protein expression of the Ca2+-dependent adenylyl cyclases
      (AC) AC3 and AC6 was up- and down-regulated, respectively. Like STIM1 knockdown,
      application of the calmodulin inhibitor W7 lowered cAMP levels, further
      indicating that STIM1 regulates AC3 via Ca2+ We conclude that the high levels of
      STIM1 in ADPKD cells play a role in supporting cyst growth and promoting high
      cAMP levels and an increased release of Ca2+ from the ER. Thus, our results
      provide novel therapeutic targets for treating ADPKD.

PMID- 30296478
TI  - To treat or not to treat: The minimally symptomatic EoE patient.

PMID- 30296480
TI  - RNA interference against the putative insulin receptor substrate gene chico
      affects metamorphosis in Leptinotarsa decemlineata.
AB  - It is noted that insect insulin/insulin-like growth factor/target of rapamycin
      signaling is critical for the regulation of metamorphosis in holometabolous
      insects. However, the molecular mechanism remains undetermined. Our previous
      findings reveal that RNA interference (RNAi)-mediated knockdown of an insulin
      gene (LdILP2) in Leptinotarsa decemlineata disturbs both 20-hydroxyecdysone (20E)
      and juvenile hormone (JH) signaling, and impairs pupation. In the present paper,
      we further observed that the expression of the insulin receptor substrate gene
      chico (Ldchico) and the phosphoinositide-3-kinase gene pi3k (Ldpi3k92E) was
      repressed in LdILP2 depleted larvae. Moreover, RNAi of Ldchico or Ldpi3k92E
      decreased food consumption, affected absorption and metabolism of amino acids and
      sugars, and reduced expression of several 20E (LdEcR, LdHR3 and LdE75) and JH
      (LdJHAMT, LdKr-h1 and LdHairy) signaling genes. As a result, larval development
      was postponed and larval growth was inhibited. Intriguingly, knockdown of
      Ldchico, rather than Ldpi3k92E, impaired larval-pupal and pupal-adult ecdysis,
      and specifically repressed transcription of another 20E signaling gene LdUSP.
      Ingestion of 20E rescued the expression of LdEcR, LdHR3 and LdE75, whereas 20E
      feeding restored neither the decreased LdUSP mRNA level, nor the reduced pupation
      and adult emergence rates in Ldchico RNAi larvae. Therefore, Chico is critical
      for the regulation of larval-pupal-adult transition by a PI3K-independent
      pathway, perhaps through activation of USP in L. decemlineata.

PMID- 30296479
TI  - Employment, Insurance, and Financial Experiences of Patients with Chronic Graft
      versus-Host Disease in North America.
AB  - Understanding the socioeconomic impact of chronic graft-versus-host disease
      (GVHD) on affected patients is essential to help improve their overall well
      being. Using data from the Chronic GVHD Consortium, we describe the insurance,
      employment, and financial challenges faced by these patients and the factors
      associated with the ability to work/attend school and associated financial
      burdens. A 15-item cross-sectional questionnaire designed to measure financial
      concerns, income, employment, and insurance was completed by 190 patients
      (response rate, 68%; 10 centers) enrolled on a multicenter Chronic GVHD
      Consortium Response Measures Validation Study. Multivariable logistic regression
      models examined the factors associated with financial burden and ability to
      work/attend school. The median age of respondents was 56 years, and 87% of the
      patients were white. A higher proportion of nonrespondents had lower income
      before hematopoietic cell transplantation and less than a college degree. All but
      1 patient had insurance, 34% had faced delayed/denied insurance coverage for
      chronic GVHD treatments, and 66% reported a financial burden. Patients with a
      financial burden had greater depression/anxiety and difficulty sleeping. Nonwhite
      race, lower mental functioning, and lower activity score were associated with a
      greater likelihood of financial burden. Younger age, early risk disease, and
      higher mental functioning were associated with a greater likelihood of being able
      to work/attend school. In this multicenter cohort of patients with chronic GVHD,
      significant negative effects on finances were observed even with health insurance
      coverage. Future research should investigate potential interventions to provide
      optimal and affordable care to at-risk patients and prevent long-term adverse
      financial outcomes in this vulnerable group.

PMID- 30296481
TI  - Expression profiling and functional characterization of galectin-3 of turbot
      (Scophthalmus maximus L.) in host mucosal immunity.
AB  - Galectins, a family of evolutionary conserved beta-galactoside-binding proteins,
      have been characterized in a wide range of species. Galectin-3 is the only member
      in the chimera type, which is a monomeric lectin with one CRD domain. A growing
      body of evidence have indicated vital roles of galectin-3 in innate immune
      responses against infection. Here, one galectin-3 gene was captured in turbot
      (SmLgals3) with a 1203 bp open reading frame (ORF). In comparison to other
      species, SmLgals3 showed the highest similarity and identity to large yellow
      croaker and medaka, respectively. The genomic structure analysis showed that
      SmLgals3 had 5 exons similar to other vertebrate species. The syntenic analysis
      revealed that galectin-3 had the same neighboring genes across all the selected
      species, which suggested the synteny encompassing galectin-3 region during
      vertebrate evolution. Subsequently, SmLgals3 was widely expressed in all the
      examined tissues, with the highest expression level in brain and the lowest
      expression level in skin. In addition, SmLgals3 was significantly down-regulated
      in intestine following both Gram-negative bacteria Vibrio anguillarum, and Gram
      positive bacteria Streptococcus iniae immersion challenge. Finally, the rSmLgals3
      showed strong binding ability to all the examined microbial ligands. Taken
      together, our results suggested SmLgals3 played vital roles in fish innate immune
      responses against infection. However, the knowledge of SmLgals3 are still limited
      in teleost species, further studies should be carried out to better characterize
      its detailed roles in teleost mucosal immunity.

PMID- 30296482
TI  - Influenza vaccination coverage among US-Mexico land border crossers: 2009 H1N1
      pandemic and 2011-2012 influenza season.
AB  - BACKGROUND: The high volume of US-Mexico land border crossings can facilitate
      international dissemination of influenza viruses. METHODS: We surveyed adult
      pedestrians crossing into the United States at two international land ports of
      entry to assess vaccination coverage during the 2009H1N1 influenza pandemic and
      2011-2012 influenza season. RESULTS: Of 559 participants in 2010, 23.4% reported
      receipt of the 2009H1N1 vaccine. Of 1423 participants in 2012, 33.7% received the
      2011-2012 influenza vaccine. Both years, those crossing the border >=8 times per
      month had lower vaccination coverage than those crossing less frequently. US
      border residents had lower H1N1 coverage than those in other locations.
      Vaccination coverage was higher for persons age >=65 years and, in 2010 only,
      those with less than high school education. Although most participants believed
      it is important to get vaccinated, only half believed the influenza vaccine was
      safe and effective. The main reasons for not receiving the influenza vaccine were
      beliefs of low risk of disease, time constraints, and concerns about vaccine
      safety (in 2010) or efficacy (in 2012). CONCLUSIONS: International land border
      crossers are a large and unique category of travelers that require targeted
      binational strategies for influenza vaccination and education.

PMID- 30296483
TI  - Factors associated with severity of tick-borne encephalitis: A prospective
      observational study.
AB  - BACKGROUND: Information on parameters associated with the severity of tick-borne
      encephalitis (TBE) is limited. METHODS: The association between 15 pre-defined
      parameters and the severity of TBE was evaluated in 717 consecutive adult
      patients diagnosed in Slovenia 2007-2012. RESULTS: Multivariable logistic
      regression showed that patient age (odds ratio, OR 1.26, 95% CI 1.11-1.44; P =
      0.001), previous vaccination against TBE (OR 14.23, 95% CI 1.72-117.87; P =
      0.014), blood leukocyte count (OR 1.45, 95% CI 1.13-1.85; P = 0.004), and level
      of specific TBE virus serum IgG antibodies (OR 0.85, 95% CI 0.75-0.96; P = 0.009)
      were associated with severe acute illness based on the clinical diagnosis. When
      severity of TBE was based on the severity score and linear regression was used,
      corresponding association was found for age (estimated coefficient, EC 1.70, 95%
      CI 1.06-2.33; P<0.001), previous vaccination against TBE (EC 11.16, 95% CI 5.05
      17.27; P < 0.001), serum C-reactive protein level (EC 1.20, 95% CI 0.48-1.91; P =
      0.001), and level of specific TBE virus serum IgG antibodies (EC -0.74, 95% CI 
      1.27-0.20; P = 0.007). CONCLUSIONS: Previous vaccination against TBE, low levels
      of TBE virus serum IgG antibodies, older age, higher blood leukocyte count, and
      higher serum C-reactive protein levels are associated with more severe TBE.

PMID- 30296484
TI  - Smoking cessation strategies in pregnancy: Current concepts and controversies.
AB  - Smoking during pregnancy is a risk factor associated with adverse pregnancy
      outcomes. Despite the fact that these outcomes are well known, a considerable
      proportion of pregnant women continue to smoke during this critical period. This
      paper evaluates critically smoking cessation interventions targeting pregnant
      women. We describe the findings of key published studies, review papers and
      expert statements to report the efficacy and safety of strategies for smoking
      cessation in pregnancy, including counselling and pharmacotherapy. Counselling
      appears to improve quit rates but mainly when used in combination with
      pharmacological therapy. Pharmacotherapy is recommended for women who are heavy
      smokers and are unable to quit smoking on their own. Nicotine replacement therapy
      is a reasonable first-line drug option. It is recommended that women who are
      pregnant, or planning to become pregnant, should be informed of potential risks
      for the foetus before considering smoking cessation therapy with bupropion or
      varenicline. Pregnant women view electronic nicotine delivery systems as being
      safer than combustible cigarettes, and this indeed may be the case; however,
      further evidence is required to assess their effectiveness as a smoking cessation
      aid and their safety for the mother and the child. Postpartum relapse is a
      significant problem, with approximately one out of two quitters relapsing in the
      first 2 months after delivery. These women should be considered 'at risk' and
      provided with ongoing support.

PMID- 30296485
TI  - Critical Appraisal of Programmed Death Ligand 1 Reflex Diagnostic Testing:
      Current Standards and Future Opportunities.
AB  - INTRODUCTION: Patient suitability to anti-programmed death ligand 1 (PD-L1)
      immune checkpoint inhibition is key to the treatment of NSCLC. We present,
      applied to PD-L1 testing: a comprehensive cross-validation of two
      immunohistochemistry (IHC) clones; our descriptive experience in diagnostic
      reflex testing; the concordance of IHC to in situ RNA (RNA-ISH); and application
      of digital pathology. METHODS: Eight hundred thirteen NSCLC tumor samples
      collected from 564 diagnostic samples were analyzed prospectively, and 249
      diagnostic samples analyzed retrospectively in tissue microarray format.
      Validated methods for IHC and RNA-ISH were tested in tissue microarrays and full
      sections and the QuPath system were used for digital pathology analysis. RESULTS:
      Antibody concordance of clones SP263 and 22C3 validation was 97% to 98% in
      squamous cell carcinoma and adenocarcinomas, respectively. Clinical NSCLC cases
      were reported as PD-L1-negative (48%), 1% to 49% (23%), and more than 50% (29%),
      with differences associated to tissue-type and EGFR status. Comparison of IHC and
      RNA-ISH was highly concordant in both subgroups. Comparison of digital assessment
      versus manual assessment was highly concordant. Discrepancies were mostly around
      the 1% clinical threshold. Challenging IHC interpretation included 1) calculating
      the total tumor cell denominator and the nature of PD-L1 expressing cell
      aggregates in cytology samples; 2) peritumoral expression of positive immune
      cells; 3) calculation of positive tumor percentages around clinical thresholds;
      and 4) relevance of the 100 malignant cell rule. CONCLUSIONS: Sample type and
      EGFR status dictate differences in the expected percentage of PD-L1 expression.
      Analysis of PD-L1 is challenging, and interpretative guidelines are discussed. PD
      L1 evaluations by RNA-ISH and digital pathology appear reliable, particularly in
      adenocarcinomas.

PMID- 30296486
TI  - Detection of Minimal Residual Disease Using ctDNA in Lung Cancer: Current
      Evidence and Future Directions.
AB  - Advances in DNA sequencing methods have significantly expanded the potential
      clinical applications of analyzing circulating tumor DNA (ctDNA). This genetic
      information can identify the presence of targetable mutations and has been
      explored for cancer screening purposes. ctDNA can be obtained without the risks
      inherent to biopsy, allowing for serial assessments over time. Several studies
      have additionally suggested that ctDNA can be used to detect the presence of
      minimal residual disease (MRD) after surgical resection in several cancer types,
      including lung cancer. The ability to detect MRD would allow clinicians to tailor
      adjuvant therapies, which carry risks of significant toxicities and may benefit
      only select groups of patients. Here, we review the current state of ctDNA
      profiling methods and evaluate the evidence supporting the use of ctDNA analysis
      to assess for MRD. We discuss how MRD detection could help identify patients at
      increased risk of disease recurrence and thus guide treatment decisions for
      resectable lung cancer. Finally, we propose future steps to validate such
      approaches and expand the utility of these rapidly progressing technologies.

PMID- 30296487
TI  - A nanoencapsulation suspension biomimetic of milk structure for enhanced maternal
      and fetal absorptions of DHA to improve early brain development.
AB  - Docosahexaenoic acid (DHA) is one omega-3 fatty acid that is essential for the
      development and function of the brain. However, a large number of clinical trials
      found that the DHA supplementation showed no advantage on mental and motor skill
      development in term infants. A strategy based on DHA nanoencapsulation (nano FO)
      using an edible plant protein, zein, mimicking the milk structure is applied for
      enhanced maternal and fetal absorptions of DHA to improve early brain
      development. The nano FO achieved increased absorption in GI tract, enhanced
      delivery to the maternal, fetal, and offspring brains, and reduced fatty acid
      accumulation in the fetal liver. In the behavior assessments, the nano FO diet
      showed enhanced learning and memory improvement compared to the normal FO diet.
      It indicated that zein nanoencapsulation is with high potential for drug and
      nutrient deliveries to brain and through placenta to fetus with no toxicity
      concern.

PMID- 30296489
TI  - Isolevuglandins and cardiovascular disease.
AB  - Isolevuglandins are 4-ketoaldehydes formed by peroxidation of arachidonic acid.
      Isolevuglandins react rapidly with primary amines including the lysyl residues of
      proteins to form irreversible covalent modifications. This review highlights
      evidence for the potential role of isolevuglandin modification in the disease
      processes, especially atherosclerosis, and some of the tools including small
      molecule dicarbonyl scavengers utilized to assess their contributions to disease.

PMID- 30296488
TI  - The immune-metabolic regulatory roles of epoxyeicosatrienoic acids on macrophages
      phenotypic plasticity in obesity-related insulin resistance.
AB  - Macrophages in adipose tissue are associated with obesity-induced low-grade
      inflammation, which contributed to insulin resistance and the related metabolic
      diseases. Macrophages display phenotypic plasticity, and polarize under the
      condition of obesity. Epoxyeicosatrienoic Acids (EETs) are lipid mediators that
      are involved in the regulation of inflammatory cascades and glucose homeostasis.
      In this mini-review, we briefly summarize the macrophages recruitment,
      infiltration and polarization in obese mice, and also discuss the immune
      metabolic regulatory role of EETs in this process (See Fig. 1).

PMID- 30296490
TI  - Eicosanoids via CYP450 and cardiovascular disease: Hints from genetic and
      nutrition studies.
AB  - Metabolites of arachidonic acid via CYP450 such as epoxyeicosatrienoic acids
      (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE), have vasoactive and
      natriuretic properties and have been implicated in BP homeostasis and the
      incidence of cardio- and cerebrovascular diseases in animal studies. In humans,
      genetic studies considering genes implicated in arachidonic acids metabolism
      (CYP4F2, CYP4A11, CYP2J2, CYP2C8, CYP2C9, CYP2A1/2, EPHX2) can offer a hint to
      understand their role, if any, in hypertension development and its deleterious
      cardiovascular effects. Candidate genes studies and successive meta-analyses have
      shown that specific single nucleotide polymorphisms (SNPs), often functional, and
      haplotypes in these genes were associated with one or more cardiovascular
      endpoints. Nevertheless, genome wide association studies (GWAS) have never
      detected any SNPs nearby these genes (the only exception being the CYP2A1/2
      locus) as associated with either BP, hypertension, coronary artery disease or
      stroke questioning their real importance for cardiovascular health in humans.
      Nutrition studies exploring the effects of specific foods on the formation of
      these compounds or others through the same pathway can offer new insights on this
      field.

PMID- 30296491
TI  - relSCAN - A system for extracting chemical-induced disease relation from
      biomedical literature.
AB  - This paper proposes an effective and robust approach for Chemical-Induced Disease
      (CID) relation extraction from PubMed articles. The study was performed on the
      Chemical Disease Relation (CDR) task of BioCreative V track-3 corpus. The
      proposed system, named relSCAN, is an efficient CID relation extraction system
      with two phases to classify relation instances from the Co-occurrence and Non-Co
      occurrence mention levels. We describe the case of chemical and disease mentions
      that occur in the same sentence as 'Co-occurrence', or as 'Non-Co-occurrence'
      otherwise. In the first phase, the relation instances are constructed on both
      mention levels. In the second phase, we employ a hybrid feature set to classify
      the relation instances at both of these mention levels using the combination of
      two Machine Learning (ML) classifiers (Support Vector Machine (SVM) and J48
      Decision tree). This system is entirely corpus dependent and does not rely on
      information from external resources in order to boost its performance. We
      achieved good results, which are comparable with the other state-of-the-art CID
      relation extraction systems on the BioCreative V corpus. Furthermore, our system
      achieves the best performance on the Non-Co-occurrence mention level.

PMID- 30296493
TI  - It's complicated... m6A-dependent regulation of gene expression in cancer.
AB  - Cellular function relies on multiple pathways that are coordinated to ensure the
      proper execution of gene expression networks. Failure to coordinate the multiple
      programs active in the cell can have catastrophic consequences and lead to
      diseases such as cancer. At the post-transcriptional level, RNA modifications
      play important roles in the regulation of gene expression. N6-methyladenosine
      (m6A) is the most abundant internal messenger RNA (mRNA) modification and has
      gained increasing interest in the last few years as a dynamic regulator of RNA
      metabolism. Modifications regulate all stages of the RNA life cycle, from
      transcription to decay. Recent studies have pointed to the role of RNA
      methylation in cancer initiation and progression, and aberrant modification has
      served as a biomarker of early-stage diagnosis in several cancers. Here, we
      review the regulation of m6A, disruptions to methylation-dependent pathways that
      influence carcinogenesis, and potential avenues for m6A-related therapeutic
      strategies.

PMID- 30296492
TI  - Using Scipion for stream image processing at Cryo-EM facilities.
AB  - Three dimensional electron microscopy is becoming a very data-intensive field in
      which vast amounts of experimental images are acquired at high speed. To manage
      such large-scale projects, we had previously developed a modular workflow system
      called Scipion (de la Rosa-Trevin et al., 2016). We present here a major
      extension of Scipion that allows processing of EM images while the data is being
      acquired. This approach helps to detect problems at early stages, saves computing
      time and provides users with a detailed evaluation of the data quality before the
      acquisition is finished. At present, Scipion has been deployed and is in
      production mode in seven Cryo-EM facilities throughout the world.

PMID- 30296494
TI  - Epigenetic dynamic during endochondral ossification and articular cartilage
      development.
AB  - Within the last decade epigenetics has emerged as fundamental regulator of
      numerous cellular processes, including those orchestrating embryonic and fetal
      development. As such, epigenetic factors play especially crucial roles in
      endochondral ossification, the process by which bone tissue is created, as well
      during articular cartilage formation. In this review, we summarize the recent
      discoveries that characterize how DNA methylation, histone post-translational
      modifications and non-coding RNA (e.g., miRNA and lcnRNA) epigenetically regulate
      endochondral ossification and chondrogenesis.

PMID- 30296495
TI  - Fertility, fecundity and the creative instinct.

PMID- 30296496
TI  - Mutant p53 prevents GAPDH nuclear translocation in pancreatic cancer cells
      favoring glycolysis and 2-deoxyglucose sensitivity.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and
      devastating human malignancies. In about 70% of PDACs the tumor suppressor gene
      TP53 is mutated generally resulting in conformational changes of mutant p53
      (mutp53) proteins, which acquire oncogenic functions triggering aggressiveness of
      cancers and alteration of energetic metabolism. Here, we demonstrate that mutant
      p53 prevents the nuclear translocation of the glycolytic enzyme glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) stabilizing its cytoplasmic localization, thus
      supporting glycolysis of cancer cells and inhibiting cell death mechanisms
      mediated by nuclear GAPDH. We further show that the prevention of nuclear
      localization of GAPDH is mediated by both stimulation of AKT and repression of
      AMPK signaling, and is associated with the formation of the SIRT1:GAPDH complex.
      By using siRNA-GAPDH or an inhibitor of the enzyme, we functionally demonstrate
      that the maintenance of GAPDH in the cytosol has a critical impact on the anti
      apoptotic and anti-autophagic effects driven by mutp53. Furthermore, the blockage
      of its mutp53-dependent cytoplasmic stabilization is able to restore the
      sensitivity of PDAC cells to the treatment with gemcitabine. Finally, our data
      suggest that mutp53-dependent enhanced glycolysis permits cancer cells to acquire
      sensitivity to anti-glycolytic drugs, such as 2-deoxyglucose, suggesting a
      potential personalized therapeutic approach in human cancers carrying mutant TP53
      gene.

PMID- 30296497
TI  - NF-YA enters cells through cell penetrating peptides.
AB  - Cell Penetrating Peptides -CPPs- are short aminoacidic stretches present in
      proteins that have the ability to translocate the plasma membrane and facilitate
      delivery of various molecules. They are usually rich in basic residues, and
      organized as alpha helices. NF-Y is a transcription factor heterotrimer formed by
      two Histone Fold Domain -HFD- subunits and the sequence-specific NF-YA. NF-YA
      possesses two alpha-helices rich in basic residues. We show that it efficiently
      enters cells at nanomolar concentrations in the absence of carrier peptides.
      Mutagenesis identified at least two separate CPPs in the A1 and A2, which overlap
      with previously identified nuclear localization signals (NLS). The half-life of
      the transduced protein is short in human cancer cells, longer in mouse C2C12
      myoblasts. The internalized NF-YA is capable of trimerization with the HFD
      subunits and binding to the target CCAAT box. Functionality is further suggested
      by protein transfection in C2C12 cells, leading to inhibition of differentiation
      to myotubes. In conclusion, NF-YA contains CPPs, hinting at novel -and unexpected
      properties of this subunit.

PMID- 30296498
TI  - The cytosolic peroxisome-targeting signal (PTS)-receptors, Pex7p and Pex5pL, are
      sufficient to transport PTS2 proteins to peroxisomes.
AB  - Proteins harboring peroxisome-targeting signal type-2 (PTS2) are recognized in
      the cytosol by mobile PTS2 receptor Pex7p and associate with a longer isoform
      Pex5pL of the PTS1 receptor. Trimeric PTS2 protein-Pex7p-Pex5pL complexes are
      translocated to peroxisomes in mammalian cells. However, it remains unclear
      whether Pex5pL and Pex7p are sufficient cytosolic components in transporting of
      PTS2 proteins to peroxisomes. Here, we construct a semi-intact cell import system
      to define the cytosolic components required for the peroxisomal PTS2 protein
      import and show that the PTS2 pre-import complexes comprising Pex7p, Pex5p, and
      Hsc70 isolated from the cytosol of pex14 Chinese hamster ovary cell mutant ZP161
      is import-competent. PTS2 reporter proteins are transported to peroxisomes by
      recombinant Pex7p and Pex5pL in semi-intact cells devoid of the cytosol.
      Furthermore, PTS2 proteins are translocated to peroxisomes in the presence of a
      non-hydrolyzable ATP analogue, adenylyl imidodiphosphate, and N-ethylmaleimide,
      suggesting that ATP-dependent chaperones including Hsc70 are dispensable for PTS2
      protein import. Taken together, we suggest that Pex7p and Pex5pL are the minimal
      cytosolic factors in the transport of PTS2 proteins to peroxisomes.

PMID- 30296499
TI  - Clostridium difficile toxin B induces senescence in enteric glial cells: A
      potential new mechanism of Clostridium difficile pathogenesis.
AB  - Clostridium difficile infection (CDI) causes nosocomial/antibiotic-associated
      diarrhea and pseudomembranous colitis, with dramatic incidence/mortality
      worldwide. C. difficile virulence factors are toxin A and toxin B (TcdB) which
      cause cytopathic/cytotoxic effects and inflammation. Until now studies were
      focused on molecular effects of C. difficile toxins (Tcds) on different cells
      while unexplored aspect is the status/fate of cells that survived their
      cytotoxicity. Recently we demonstrated that enteric glial cells (EGCs) are
      susceptible to TcdB cytotoxicity, but several EGCs survived and were irreversibly
      cell-cycle arrested and metabolically active, suggesting that EGCs could became
      senescent. This is important because allowed us to evaluate the not explored
      status/fate of cells surviving Tcds cytotoxicity, and particularly if TcdB
      induces senescence in EGCs. Rat-transformed EGCs were treated with 10 ng/ml TcdB
      for 6 h-48 h, or for 48 h, followed by incubation for additional 4 or 11 days in
      absence of TcdB (6 or 13 total days). Senescence markers/effectors were examined
      by specific assays. TcdB induces senescence in EGCs, as demonstrated by the
      senescence markers: irreversible cell-cycle arrest, senescence-associated-beta
      galactosidase positivity, flat morphology, early and persistent DNA damage (ATM
      and H2AX phosphorylation), p27 overexpression, pRB hypophosphorylation, c-Myc,
      cyclin B1, cdc2 and phosphorylated-cdc2 downregulation, Sirtuin-2 and Sirtuin-3
      overexpression. TcdB-induced EGC senescence is dependent by JNK and AKT
      activation but independent by ROS, p16 and p53/p21 pathways. In conclusion, TcdB
      induces senescence in EGCs. The extrapolation of these results to CDI leads to
      hypothesize that EGCs that survived TcdB, once they have acquired a senescence
      state, could cause irritable bowel syndrome (IBS), inflammatory bowel disease
      (IBD), and tumors due to persistent inflammation, transfer of senescence status
      and stimulation of pre-neoplastic cells.

PMID- 30296500
TI  - Cofilin-1 signaling mediates epithelial-mesenchymal transition by promoting actin
      cytoskeleton reorganization and cell-cell adhesion regulation in colorectal
      cancer cells.
AB  - Colorectal cancer (CRC) is frequently a lethal disease because of metastasis.
      Actin cytoskeletal rearrangement is an essential step in cell migration during
      activation of the epithelial-mesenchymal transition (EMT) program, which is
      associated with metastatic properties of cancer cells. Cofilin-1 protein
      modulates actin dynamics by promoting actin treadmilling, thereby driving
      membrane protrusion and cell migration and invasion. However, the role of cofilin
      1 during EMT in CRC is unknown. Here, we show that cofilin-1 and p-cofilin-1 have
      distinct subcellular distribution in EMT cells, as determined by super-resolution
      microscopy images, indicating distinct roles in different areas of cells.
      Silenced cofilin-1 cells treated with TGF-beta (siCofilin-1/TGF-beta) evaded p
      LIMK2-p-cofilin-1 status, leading to recovery of E-cadherin and claudin-3 at the
      cell-cell contact and their respective protein levels, actin reorganization, and
      decreased mesenchymal protein level. Furthermore, siCofilin-1/TGF-beta cells
      exhibited decreased migration and invasion rates as well as MMP-2 and -9 activity
      and augmented focal adhesion size. The expression of an inactive phospho-cofilin
      1 mimetic (S3E) reduced E-cadherin and claudin-3 in cell-cell contacts, reduced
      their protein levels, and increased vimentin protein. Based on our findings, we
      suggest that cofilin-1 is crucial to switching from epithelial to mesenchymal
      like morphology and cell migration and invasion by regulating actin cytoskeleton
      organization through activation of RhoA-LIMK2-cofilin-1 signaling, impacting the
      cell-cell adhesion organization of colon cancer cells in EMT.

PMID- 30296501
TI  - Recurrent Urinary Tract Infections are Associated With Frailty in Older Adults.
AB  - OBJECTIVE: To understand the relationship between frailty, age, and recurrent
      urinary tract infections (rUTIs). MATERIALS AND METHODS: The Timed Up and Go Test
      (TUGT), a measure of frailty, was administered to all adults aged >=65 presenting
      to an academic nononcologic urology practice from December 2015 to January 2018.
      TUGT was categorized as fast (<=10 seconds), intermediate (11-14 seconds) or slow
      (>=15 seconds). The TUGT and other clinical data were abstracted from the medical
      record using direct queries supplemented with chart review. Logistic regression
      was used to determine the relationship between frailty, age, and the diagnosis of
      rUTIs in our clinic population. RESULTS: There were 136 americans adults with and
      2824 americans adults without a diagnosis of rUTIs. Individuals with rUTIs had
      slower TUGT times (13.8 +/- 10.4 seconds compared to 10.8 +/- 4.52 seconds, P
      <.01) and were more likely to be classified as slow, or "frail" (27.2% vs 10.8%).
      In multivariate analysis, slow TUGT times were associated with a diagnosis of
      rUTIs (adjusted OR 2.0, 95% CI 1.2-3.3), while age was not a statistically
      significant predictor of this diagnosis (adjusted OR 1.3, 95% CI 0.7-2.2 for aged
      >=81 years). CONCLUSION: Older adults with a diagnosis of rUTIs are significantly
      more frail compared to those with other nononcologic urologic diagnoses. Frailty
      (adjusted for age), was significantly associated with rUTIs, while age (adjusted
      for frailty) was not. Furthermore, frailty (rather than age) may be important to
      consider when caring for and treating americans adults with rUTIs.

PMID- 30296502
TI  - Surgical Management of Patients with Advanced Germ Cell Tumors Following Salvage
      Chemotherapy: Memorial Sloan Kettering Cancer Center (MSKCC) Experience.
AB  - OBJECTIVE: To characterize clinical and pathologic outcomes of cisplatin
      refractory or relapsed germ cell tumor (GCT) patients who underwent
      retroperitoneal lymph node dissection (RPLND) following salvage chemotherapy with
      either conventional or high dose regimens. METHODS: Data were reviewed to
      identify all patients treated with TIP or TICE salvage chemotherapy between 1994
      and 2011(n = 184) at our institution. We report clinicopathologic and outcomes
      data on 131 patients who were further managed with surgical resection. Using Cox
      proportional hazards models, predictors of disease-specific survival (DSS) were
      analyzed. RESULTS: Median follow-up was 7.3 years. Of the 112 patients who
      underwent postsalvage chemotherapy RPLND, histology was reported as viable GCT in
      30 (27%), teratoma only in 26 (23%) and fibrosis in 56 (50%). 5-year DSS for the
      entire cohort was 74% (95% confidence interval 63%-80%). On multivariable
      analysis, viable GCT histology at RPLND or extra-RPLND resection predicted for
      worse DSS (hazard ratio 7.37, P = .003). CONCLUSIONS: Our data suggest that
      approximately half of the patient with cisplatin-refractory or relapsed GCT
      salvaged with TIP or TICE chemotherapy and evidence of residual disease are at
      risk of harboring either viable GCT or teratoma. This finding underlines the
      critical role of surgery in the multimodality approach to the management of this
      advanced disease entity. If retroperitoneal disease exists prior to salvage
      chemotherapy, we recommend postchemotherapy resection in all eligible patients.

PMID- 30296503
TI  - Renal Hilar Lesions: Biological Implications for Complex Partial Nephrectomy.
AB  - OBJECTIVE: To perform a comprehensive histopathologic review of sporadic resected
      solitary cT1 renal masses comparing those with and without radiographic
      involvement of the hilum. MATERIALS AND METHODS: A prospectively maintained
      database was queried for all cT1 renal masses undergoing resection classified per
      the R.E.N.A.L. nephrometry score. Hilar masses were defined as tumors that abut
      the main renal artery or vein on cross-sectional imaging. Demographic, treatment,
      renal mass, and histopathologic characteristics were compared between hilar and
      nonhilar renal masses. Multivariate regression model analyses were performed to
      assess factors associated with renal mass upstaging and disease recurrence.
      RESULTS: A total of 1324 stage 1 renal masses met criteria for analysis of which
      226 (17.1%) were defined as hilar. Hilar masses were larger, scored with higher
      complexity, and more likely to undergo a radical nephrectomy. On histopathologic
      analysis, we found no difference between hilar and nonhilar masses regarding the
      incidence of malignancy, presence of high nuclear grade, or risk of upstaging. On
      multivariate analysis, a tumor's hilar location was not associated with upstaging
      or disease recurrence. CONCLUSION: We present a comprehensive histopathologic
      review of a large cohort of cT1 hilar lesions noting no difference in the risk of
      malignancy, high nuclear grade, upstaging, or recurrence when compared to
      nonhilar lesions. Together, these data suggest that there is no compelling cancer
      specific rationale to perform a radical nephrectomy when managing renal hilar
      tumors.

PMID- 30296504
TI  - Dopamine genetic risk is related to food addiction and body mass through reduced
      reward-related ventral striatum activity.
AB  - The prevalence rate of obesity continues to rise in the U.S., but effective
      treatment options remain elusive resulting in increased emphasis on prevention.
      One such area of prevention research capitalizes on the relatively novel
      behavioral construct of food addiction, which has been implicated in obesity.
      Food addiction reflects an individual's propensity for compulsive eating despite
      negative consequences, and shares not only symptoms with both eating and
      substance use disorders but also genetic and neural correlates within neural
      reward-circuitry modulated by dopamine. Here, we examined associations between
      food addiction scores, body mass index (BMI), reward-related ventral striatum
      activity, and a polygenic score approximating dopamine signaling in 115 non
      Hispanic Caucasian young adult university students. As predicted, polygenic
      dopamine scores were related to ventral striatum activity, which in turn was
      associated with higher food addiction scores. In addition, food addiction was
      related to BMI. An exploratory post-hoc path analysis further indicated that
      polygenic scores were indirectly related to both food addiction and BMI, in part,
      through ventral striatum activity. Collectively, our results provide evidence
      supporting the utility of food addiction in weight gain prevention research by
      establishing links with known risk-related neural and genetic biomarkers.

PMID- 30296505
TI  - Association between eating frequency and eating behaviours related to appetite
      from 4 to 7 years of age: Findings from the population-based birth cohort
      generation XXI.
AB  - The examination of specific characteristics of eating habits in childhood and its
      influence on eating behaviours is needed to better understand the establishment
      of appetite-related eating behaviours. This study aimed to assess the association
      between eating frequency (EF) (main meals vs. snacks) at 4 and 7y and problematic
      eating behaviours and appetite-related eating behaviours at 7y. The analysis
      included 1359 children from the birth cohort Generation XXI who provided 3-day
      food diaries, at both ages, and complete information on the Child Eating
      Behaviour Questionnaire, at 7y. Problematic eating behaviours were assessed using
      parental perception of child's poor eating (including not eating enough, eating
      too slow or overeating) at both ages. A time-of-day approach was used to
      distinguish main meals from snacks. A cross-lagged analysis was performed to
      check the direction of the association between EF and parental concerns regarding
      problematic eating behaviours. Associations between EF and appetite-related
      eating behaviours were evaluated through linear regression models. Between 4 and
      7y a moderate tracking of EF was described as well as a strong tracking of
      parental concerns. We found a bidirectional relationship between EF and parental
      concerns. Prospectively, a higher frequency of snacks at 4y was independently
      associated with higher scores in 'Desire to Drink' at 7y (beta = 0.051,
      95%CI:0.009; 0.093). At 7y, a higher EF had a positive association with 'Satiety
      Responsiveness' but an inverse association with 'Enjoyment of Food'. A higher
      number of main meals had a positive association with 'Enjoyment of Food' and
      'Food Responsiveness'. In conclusion, children who had more eating occasions seem
      to have more food-avoidance behaviours, traits that might protect these children
      from gaining excessive weight.

PMID- 30296506
TI  - Response characteristics of the cat somatosensory cortex following the mechanical
      stimulation to endodontically treated teeth with overextension.
AB  - The overextension of filling materials may take place accidentally during an
      endodontic root canal treatment. Previous studies to understand the correlation
      between overfilling and paresthesia of teeth were inconsistent. In this study, an
      intrinsic signal optical imaging technique was employed as the objective tool to
      compare the response characteristics of the cat somatosensory cortex following
      mechanical stimulation applied to endodontically treated teeth with overextension
      (ETTWO) and natural teeth. Based on the evoked cortical response, the signal
      strength of the ETTWO was found to be significantly higher than that of the
      natural teeth. However, the tactile threshold of the ETTWO was significantly
      lower than that of the natural teeth. It was concluded that the tactile function
      of ETTWO is more sensitive than that of natural teeth, and that the overextension
      of filling materials can cause hyperesthesia of teeth after root canal treatment.

PMID- 30296507
TI  - Aging alters glucose uptake in the naive and injured rodent spinal cord.
AB  - Aging results in increased activation of inflammatory glial cells and decreased
      neuronal viability following spinal cord injury (SCI). Metabolism and transport
      of glucose is also decreased with age, although the influence of age on glucose
      transporter (GLUT) expression or glucose uptake in SCI is currently unknown. We
      therefore performed [18F]Fluorodeoxyglucose (FDG) PET imaging of young (3 month)
      and middle-aged (12 month) rats. Glucose uptake in middle-aged rats was decreased
      compared to young rats at baseline, followed by increased uptake 14 days post
      contusion SCI. qRT-PCR and protein analysis revealed an association between 14
      day glucose uptake and 14 day post-injury inflammation. Further, gene expression
      analysis of neuron-specific GLUT3 and non-specific GLUT4 (present on glial cells)
      revealed an inverse relationship between GLUT3/4 gene expression and glucose
      uptake patterns. Protein expression revealed increased GLUT3 in 3 month rats
      only, consistent with age related decreases in glucose uptake, and increased
      GLUT4 in 12 month rats only, consistent with age related increases in
      inflammatory activity and glucose uptake. Inconsistencies between gene and
      protein suggest an influence of age-related impairment of translation and/or
      protein degradation. Overall, our findings show that age alters glucose uptake
      and GLUT3/4 expression profiles before and after SCI, which may be dependent on
      level of inflammatory response, and may suggest a therapeutic avenue in
      addressing glucose uptake in the aging population.

PMID- 30296508
TI  - Substitution therapy with amphetamine-isotherapic attenuates amphetamine
      toxicological aspects of addiction.
AB  - INTRODUCTION: amphetamine (AMPH) is related to development of addiction, anxiety
      like behaviors and impairments of memory after chronic use. In the current
      experiment, an ultra-high dilution (10-24mg/mL) of AMPH was used, consisting of
      the AMPH isotherapic (AMPH-ISO), which can be used as a replacement therapy to
      treat AMPH addiction. AIM: To verify the influence of AMPH-ISO on toxicological
      aspects of AMPH addiction. METHODS: Rats received d,l-AMPH (4.0 mg/kg, i.p.) in
      the conditioned place preference (CPP) paradigm (8 days). Then, half of each
      experimental group (AMPH or saline) received AMPH-ISO/vehicle (0.2 mL per rat,
      once a day), for fourteen days. On the fifteenth day, animals were re-assessed in
      the CPP paradigm (to verify relapse behaviors) after a single dose of AMPH (2.0
      mg/kg). Subsequently, anxiety-like behaviors were quantified, followed by ex vivo
      assays in the pre-frontal cortex. RESULTS: AMPH-ISO prevented relapse-like
      behavior of AMPH and reduced anxiety-like behavior per se in animals co-treated
      with AMPH. Molecular analysis evidenced that AMPH-ISO modulated dopaminergic
      targets (dopamine transporter, tyrosine hydroxylase and D1-R), whose
      immunoreactivity was increased by AMPH. Also, AMPH-ISO increased catalase
      activity and NPSH levels and reduced lipid peroxidation and protein carbonyl
      levels in the prefrontal cortex. CONCLUSION: This study shows that an ultra-high
      dilution of AMPH may be a useful alternative which can contribute with AMPH
      addiction treatment.

PMID- 30296509
TI  - RIFM Fragrance ingredient safety assessment, 3-ethylhexahydro-2(3H)
      benzofuranone, CAS Registry Number 54491-17-7.

PMID- 30296510
TI  - RIFM fragrance ingredient safety assessment, tricyclodecenyl propionate, CAS
      Registry Number 17511-60-3.

PMID- 30296511
TI  - RIFM fragrance ingredient safety assessment, 1-naphthalenol, 1,2,3,4,4a,5,8,8a
      octahydro-2,2,6,8-tetramethyl-, CAS Registry Number 103614-86-4.

PMID- 30296512
TI  - RIFM fragrance ingredient safety assessment, terpinyl formate, CAS Registry
      Number 2153-26-6.

PMID- 30296514
TI  - Role of AMPK pathway in lead-induced endoplasmic reticulum stress in kidney and
      in paeonol-induced protection in mice.
AB  - Paeonol is a natural flavonoid isolated from Moutan Cortex, which has been found
      to exhibit antioxidant, anti-apoptotic, anti-aging and anti-inflammatory
      bioactivities. Herein, we investigated the nephroprotective efficacy of paeonol
      against Pb-induced toxicity and elucidated the potential mechanisms. The results
      revealed that paeonol significantly ameliorated renal dysfunction and histology
      changes of Pb-treated mice. Paeonol inhibited oxidative stress and increased
      activities of antioxidant enzyme in the kidneys of Pb-treated mice. Paeonol
      decreased the nuclear factor-kappaB activation and over-production of
      inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6
      (IL-6). Paeonol suppressed endoplasmic reticulum (ER) stress in kidneys of in the
      Pb treatment group and primary kidney mesangial cells. Moreover, paeonol
      increased the denosine 5'-monophosphate-activated protein kinase (AMPK)
      phosphorylation and decreased the activations of glycogen synthase kinase-3 (GSK
      3), protein kinase RNA-like ER kinase (PERK), inositol-requiring protein-1
      (IRE1), c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase
      (MAPK). These results were further confirmed in primary kidney mesangial cells.
      Taken together, these findings indicate that paeonol could protect kidney form Pb
      induced injury by inhibiting oxidative stress, ER stress and inflammation via the
      AMPK and GSK-3 pathway. Paeonol might be a potential therapeutic agent to inhibit
      ER stress-associated inflammation in lead-stimulated kidneys.

PMID- 30296513
TI  - RIFM fragrance ingredient safety assessment, 2,6-nonadien-1-ol, CAS Registry
      Number 7786-44-9.

PMID- 30296515
TI  - RIFM fragrance ingredient safety assessment, isophorol, CAS Registry Number 470
      99-5.

PMID- 30296516
TI  - RIFM fragrance ingredient safety assessment, 3-(cis-3-hexenyloxy)propanenitrile,
      CAS Registry Number 142653-61-0.

PMID- 30296518
TI  - Diagnosis of T-cell mediated kidney rejection in formalin fixed paraffin embedded
      tissues using RNA-Seq based machine learning algorithms.
AB  - Molecular diagnosis is being increasingly used into transplant pathology to
      render more objective and quantitative determinations that also provide
      mechanistic and prognostic insights. This study performed RNA-Seq on biopsies
      from kidneys with stable function (STA) and biopsies with classical findings of T
      cell mediated rejection (TCMR). Machine learning tools were used to develop
      prediction models for distinguishing TCMR and STA samples using the top genes
      identified by DSeq2. The prediction models were tested on 703 biopsies with
      Affymetrix chip gene expression profiles available in the public domain. Linear
      Discriminant Analysis (LDA) predicted TCMR in 55/67 biopsies labeled TCMR, 65/105
      biopsies designated as antibody-mediated rejection (ABMR). The random forest and
      support vector machine models showed comparable performance. These data
      illustrate the feasibility of using RNA-Seq for molecular diagnosis of TCMR in
      formalin fixed tissue. Application of the derived diagnostic algorithms to
      publicly available datasets demonstrates frequent co-existence of TCMR in
      biopsies designated as ABMR. This under-recognition of TCMR in renal allograft
      biopsies has significant implications with respect to patient care.

PMID- 30296519
TI  - A review of the incidence of adenocarcinoma detected during surveillance for
      Barrett's esophagus.
AB  - The objective of this study is to provide an up to date estimate of the incidence
      of adenocarcinoma detected during surveillance of Barrett's esophagus. Fifty-five
      longitudinal studies involving approximately 61000 patients were reviewed. A
      general linear model analyses with Poisson link function was used to study how
      the number of cancer cases detected depended on study details. The studies
      appeared to follow the same statistical model, and the probability of developing
      Barrett's carcinoma during surveillance was found to depend on the following
      variables: how Barrett's metaplasia was defined, the number of patients studied,
      the mean time of follow-up and the fraction of patients followed at least 5years.
      The model derived from all the studies predicted that the per person probability
      of developing cancer in 5years of complete follow-up is approximately .0012.

PMID- 30296517
TI  - RIFM fragrance ingredient safety assessment, nonyl acetate, CAS Registry Number
      143-13-5.

PMID- 30296520
TI  - HMGB2 promotes the malignancy of human gastric Cancer and indicates poor survival
      outcome.
AB  - HMGB2 is an important protein in carcinogenesis. However, little is known
      regarding the specific role of HMGB2 in gastric cancer. In present study, HMGB2
      expression was evaluated in 198 primary gastric cancer tissues and their adjacent
      non-tumor controls. The correlation between HMGB2 expression and clinic
      pathological features and survival was assessed. The effect of HMGB2 on cell
      proliferation, invasion, and glycolysis was examined in vitro. The expression of
      HMGB2 was significantly increased in human gastric cancer when compared with non
      tumor tissues (P<.001). High HMGB2 expression correlated with large tumor size
      (P0.001), advanced T stage (P=.007), and present of lymph node metastasis
      (P=.004). Moreover, high HMGB2 expression was validated as an independent
      prognostic factor in both univariate and multivariate analysis (P<.05).
      Experimentally, silencing HMGB2 expression by stable transfected shRNA
      significantly decreased the proliferation, invasion and glycolysis of gastric
      cancer cells. In conclusion, HMGB2 is a novel prognostic biomarker for survival
      in gastric cancer, and knockdown HMGB2 expression in gastric cancer cells
      attenuated proliferation and invasion, and impaired glycolysis in gastric cancer
      cells. Hence, HMGB2 may serves as a new biomarker and potential therapeutic
      target for gastric cancer.

PMID- 30296521
TI  - IDH mutation status in a series of 88 head and neck chondrosarcomas: different
      profile between tumors of the Skull Base and tumors involving the facial skeleton
      and the Layngotracheal tract.
AB  - Chondrosarcomas are rare primary malignant bone tumors that involve the head and
      neck region in 1% to 12% of cases. Central conventional chondrosarcoma is the
      most common subtype and is associated with isocitrate dehydrogenase 1 and 2 (IDH1
      and IDH2) gene mutations in 50% to 60% of cases. We aimed to define the frequency
      of IDH1 and IDH2 gene mutations in a multicenter series of 88 cases of
      chondrosarcoma of the head and neck, including tumors involving the base of the
      skull (n=30), the facial skeleton (n=11), and the laryngeal and tracheal
      cartilages (n=47). Petrous bone and cricoid cartilage were the most frequently
      involved sites for chondrosarcomas of the skull base and laryngotracheal tract
      (respectively 43.3% and 31.9%). Overall, 64.9% of craniofacial chondrosarcomas
      featured IDH mutations, with a high rate for skull-base tumors (85.7%) but no IDH
      mutations in tumors of the facial skeleton. This different mutational profile
      could be related to the type of ossification, the bones of the base of the skull
      mainly resulting from endochondral ossification and those of the face from
      intramembranous ossification. Conversely, mutation was infrequent in
      chondrosarcomas involving the laryngeal and tracheal cartilages (11.8% of 47
      cases). Evaluation of IDH mutation status may be a useful diagnostic tool for
      bone tumors of the skull base, which are most often assessable with only small
      biopsy samples. The low rate of IDH mutations observed in laryngotracheal
      chondrosarcomas suggests a different mode of tumorigenesis needing further
      exploration.

PMID- 30296522
TI  - Loss of expression of MU-protocadherin and protocadherin-24 in sporadic and
      hereditary non polyposis colorectal cancers (HNPCC).
AB  - Colorectal cancer (CRC) is a neoplastic disease in which normal mucosa undergoes
      a process of malignant transformation due to the progressive accumulation of
      molecular alterations affecting proto-oncogenes and onco-suppressor genes. Some
      of these modifications exert their carcinogenic potential by promoting a
      constitutive activation of the beta-catenin signaling proliferation pathway and,
      when present, loss of cadherin expression also significantly contributes to the
      same effect. Using a combined approach of molecular and immunohistochemical
      analysis, we have previously demonstrated that the majority of sporadic CRCs
      exhibit a down-regulated expression of a cadherin, named MU-protocadherin, that
      is generally observed in association with a higher proliferation rate and a worst
      prognosis. The aim of this report was to perform a comparative
      immunohistochemical assessment of MU-protocadherin and a similar cadherin, named
      protocadherin-24, in sporadic CRC and hereditary non polyposis colorectal cancer
      (HNPCC). The data obtained put in evidence that double negative CRCs, lacking
      both the analyzed protocadherins, are more represented among sporadic tumors
      whereas double positive CRCs, maintaining their expression, exhibit an opposite
      trend. As expected, loss of protocadherin expression was accompanied by nuclear
      localization of beta-catenin and increased positivity of the Ki-67 proliferation
      marker. This finding is consistent with the different clinical evolution of the
      two considered CRC sets according to which HNPCC patients experience a better
      prognosis as compared to those affected by a sporadic CRC.

PMID- 30296523
TI  - PD-L1 expression on tumor cells associated with favorable prognosis in surgically
      resected esophageal squamous cell carcinoma.
AB  - There is limited evidence regarding the relationship between programmed cell
      death ligand 1 (PD-L1) expression on tumor cells (TCs) and prognosis of
      esophageal squamous cell carcinoma (ESCC). This retrospective study aimed to
      investigate the clinical significance of PD-L1 expression in ESCC. To assess PD
      L1 expression, we conducted immunohistochemistry studies using a tissue
      microarray encompassing 233 ESCC cases, stage I, II, and III, with detailed
      clinical data. PD-L1 expression on TCs was observed in 55.4% (129 of 233) of ESCC
      cases and was not associated with clinicopathological factors. ESCC patients with
      PD-L1-positive tumors showed significantly better overall survival (OS) and
      disease-free survival (DFS) than those with PD-L1-negative tumors (P=.023,
      P=.026, respectively). When patients were stratified into those with stage I-II
      (127, 54.5%) and stage III (106, 45.5%) disease and those without (134, 57.5%)
      and with (99, 42.5%) lymph node metastasis, the prognostic effect was
      inconsistent. The OS and DFS of patients with positive PD-L1 expression were
      significantly better in patients with stage I-II disease (P=.021, P=.015,
      respectively) and without lymph node metastasis (P=.009, P=.07, respectively)
      than their counterparts. Our results showed that PD-L1 expression on TCs was an
      independent predictor of prognosis of ESCC patients. However, the effect varied
      in patients with different stages and lymph node status. Positive PD-L1
      expression was a favorable predictor in ESCC patients with stage I-II disease or
      without lymph node metastasis but not in patients with stage III disease or lymph
      node metastasis.

PMID- 30296524
TI  - Increased surface expression of NOTCH on memory T cells in peripheral blood from
      patients with asthma.

PMID- 30296525
TI  - Cholestenoic acid is a prognostic biomarker in acute respiratory distress
      syndrome.

PMID- 30296526
TI  - Interferon-induced epithelial response to rhinovirus 16 in asthma relates to
      inflammation and FEV1.

PMID- 30296527
TI  - Human TANK-binding kinase 1 is required for early autophagy induction upon herpes
      simplex virus 1 infection.

PMID- 30296528
TI  - Angiotensin receptor (AT2R) agonist C21 prevents cognitive decline after
      permanent stroke in aged animals-A randomized double- blind pre-clinical study.
AB  - Post stroke cognitive impairment (PSCI) is an understudied, long-term
      complication of stroke, impacting nearly 30-40% of all stroke survivors. No cure
      is available once the cognitive deterioration manifests. To our knowledge, this
      is the first study to investigate the long-term effects of C21 treatment on the
      development of PSCI in aged animals. Treatments with C21 or vehicle were
      administered orally, 24 h post-stroke, and continued for 30 days. Outcome
      measures for sensorimotor and cognitive function were performed using a sequence
      of tests, all blindly conducted and assessed at baseline as well as at different
      time points post-stroke. Our findings demonstrate that the angiotensin receptor
      (AT2R) agonist C21 effectively prevents the development of PSCI in aged animals.

PMID- 30296529
TI  - Understanding nociception-related phenotypes in adult zebrafish: behavioral and
      pharmacological characterization using the acetic acid model.
AB  - Pain, a severely debilitating symptom of many human disorders, is a growing,
      unmet biomedical problem. Although the use of zebrafish (Danio rerio) to
      investigate both behavioral and physiological nociception-related responses is
      expanding rapidly, the characterization of behavioral phenotypes that reflect
      injury location is still poorly explored, making the results of such studies
      difficult to interpret. Here, we characterize putative nociception-related
      behavioral phenotypes in adult zebrafish following an intraperitoneal (i.p.)
      administration of acetic acid, a well-established protocol for visceral pain in
      rodents. Acetic acid (2.5 and 5.0%) induced an abdominal constriction-like
      response, which was assessed by measuring a body curvature index. Moreover, all
      doses tested (0.5-5.0%) reduced distance traveled and vertical activity in the
      novel tank test. Freezing duration increased following 5.0% acetic acid, whereas
      fish injected with 1.0, 2.5, and 5.0% spent more time in top area of the tank.
      Both morphine (an opioid analgesic) and diclofenac (a nonsteroidal anti
      inflammatory drug, NSAID) prevented the 5.0% acetic acid-induced changes in body
      curvature index, whereas naloxone blocked these effects of morphine. Overall,
      zebrafish exposed to a single acetic acid i.p. injection display abnormal body
      curvature and specific changes in behavioral parameters sensitive to anti
      nociceptive pharmacological modulation. We suggest that the abdominal
      constriction-like response represents a novel specific nociceptive-related
      phenotype in zebrafish. In general, our findings support the growing utility of
      zebrafish in translational pain research and antinociceptive drug discovery.

PMID- 30296530
TI  - Adolescent social isolation increases cocaine seeking in male and female mice.
AB  - Childhood and adolescent adversity are associated with a wide range of
      psychiatric disorders, including an increased risk for substance abuse. Despite
      this, the mechanisms underlying the ability of chronic stress during adolescence
      to alter reward signaling remains largely unexplored. Understanding how
      adolescent stress increases addiction-like phenotypes could inform the
      development of targeted interventions both before and after drug use. The current
      study examined how prolonged isolation stress, beginning during adolescence,
      affected behavioral and neuronal underpinnings to the response to cocaine in male
      and female mice. Adolescent-onset social isolation did not alter the ability of
      mice to learn an operant response for food, nor influence food self
      administration or motivation for food on a progressive ratio schedule. However,
      male and female social isolation mice exhibited an increase in motivation for
      cocaine and cocaine seeking during a cue-induced reinstatement session.
      Additionally, we demonstrated that adolescent-onset social isolation increased
      cocaine-induced neuronal activation, as assessed by c-Fos expression, within the
      nucleus accumbens core and shell, ventral pallidum, dorsal bed nucleus of the
      stria terminalis, lateral septum and basolateral amygdala. Taken together, the
      present studies demonstrate that social isolation stress during adolescence
      augments the behavioral responses to cocaine during adulthood and alters the
      responsiveness of reward-related brain circuitry.

PMID- 30296531
TI  - Risky decision-making is associated with impulsive action and sensitivity to
      first-time nicotine exposure.
AB  - Excessive risk-taking is common in multiple psychiatric conditions, including
      substance use disorders. The risky decision-making task (RDT) models addiction
      relevant risk-taking in rats by measuring preference for a small food reward vs.
      a large food reward associated with systematically increasing risk of shock.
      Here, we examined the relationship between risk-taking in the RDT and multiple
      addiction-relevant phenotypes. Risk-taking was associated with elevated impulsive
      action, but not impulsive choice or habit formation. Furthermore, risk-taking
      predicted locomotor sensitivity to first-time nicotine exposure and resilience to
      nicotine-evoked anxiety. These data demonstrate that risk preference in the RDT
      predicts other traits associated with substance use disorder, and may have
      utility for identification of neurobiological and genetic biomarkers that
      engender addiction vulnerability.

PMID- 30296532
TI  - Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced
      depression.
AB  - Recent reports have demonstrated that lipopolysaccharide (LPS)-induced depressive
      like behaviour is mediated via NMDA receptor. In this study, we further
      investigated the role of GluN2 A subunit of NMDA receptor in synaptic processes
      in the prefrontal cortex (PFC) and hippocampus of GluN2 A knockout (KO) mice in
      LPS-induced depressive-like behavior. Our data suggest that LPS-treated mice,
      lacking GluN2 A subunit, did not exhibit depressive-like behaviour. This was
      accompanied by unaltered levels of IL-6 and significant changes in
      neuroplasticity markers and glutamate receptor subunits composition in PFC and
      hippocampus. In particular, an immune challenge in GluN2 A KO mice resulted in
      unchanged PSA-NCAM levels and proBDNF increase in both brain structures as well
      as in increase in BDNF levels in hippocampus. Furthermore, the absence of GluN2 A
      resulted in increased levels of all NCAM isoforms in PFC upon LPS which was
      followed with a decrease in GluN1 and GluN2B subunits. The levels of AMPA
      receptor subunits (GluA1, GluA3, and GluA4) in the hippocampus of GluN2 A mice
      were unaltered upon the treatment and abundantly present in the PFC of KO mice.
      These results indicate that the GluN2 A subunit is critical in neuroinflammation
      related depression, that its absence abolishes LPS-induced depressive phenotype,
      sustains PSA-NCAM levels, increases proBDNF signalling in the PFC and hippocampus
      and potentiates synaptic stabilization through NCAM in the PFC upon an immune
      challenge.

PMID- 30296534
TI  - Approaches to limit systemic antibiotic use in acne: Systemic alternatives,
      emerging topical therapies, dietary modification, and laser and light-based
      treatments.
AB  - Acne is one of the most common diseases worldwide and affects approximately 50
      million individuals in the United States. Oral antibiotics are the most common
      systemic agent prescribed for the treatment of acne. However, their use may be
      associated with a variety of adverse outcomes including bacterial resistance and
      disruption of the microbiome. As a result, multiple treatment guidelines call for
      limiting the use of oral antibiotics in the treatment of acne, although actual
      prescribing often does not follow these guidelines. In this review, the rationale
      for concerns regarding the use of oral antibiotics for the management of acne is
      reviewed. In addition, we will discuss our approach to complying with the intent
      of the guidelines, with a focus on novel topical agents, dietary modification,
      laser and light-based modalities, and systemic medications such as
      spironolactone, combined oral contraceptives, and oral isotretinoin.

PMID- 30296533
TI  - The use of topical rapamycin in the treatment of superficial lymphatic
      malformations.
AB  - BACKGROUND: The superficial lymphatic component of vascular malformations poses a
      significant treatment challenge. It is responsible for the majority of symptoms
      presented and to date there is no consensus regarding treatment. OBJECTIVE: To
      evaluate the effectiveness of topical rapamycin in treating superficial lymphatic
      malformations (LM). METHODS: A case series study was performed of patients with
      superficial LM, treated with topical rapamycin. The clinical characteristics of
      the patients and the concentration and application mode of the drug were
      recorded. The changes in the signs and symptoms observed, and associated adverse
      effects, were then noted and analysed. RESULTS: The study population consisted of
      11 patients, average age 10.5 years. All were treated with topical rapamycin, in
      six cases at 1%, in one at 0.8% and in four at 0.4%. Changes in the clinical
      appearance of the lesions were observed in all patients. The associated symptoms,
      present in 9 of the 11 patients, improved in every case. The mean follow-up time
      was 16.1 months. LIMITATIONS: This study is retrospective, with a small sample
      size and considerable heterogeneity of lesions and treatment approaches.
      CONCLUSIONS: Treatment with topical rapamycin modifies the clinical appearance
      and alleviates the symptoms of superficial LM.

PMID- 30296535
TI  - Relative efficacy of systemic treatments for atopic dermatitis.
AB  - BACKGROUND: Systemic medications are often required for severe atopic dermatitis
      (AD) refractory to topical therapies. Biologic medications are a recent
      advancement in the field and a comparison to traditional systemic approaches
      would be beneficial. OBJECTIVE: To compare efficacies of systemic therapies for
      the treatment of AD METHODS: A systematic literature review was performed using
      Medline, Ovid and Embase. Randomized controlled trials looking at the efficacy of
      systemic treatments for AD in adults and children were included. RESULTS: A total
      of 41 studies met criteria and were included in our final analysis. Consistent
      improvements in Eczema Area and Severity Index (EASI) and Scoring Atopic
      Dermatitis (SCORAD) were reported with dupilumab and cyclosporine. Phase 2
      clinical trials for lebrikizumab and tralokinumab were effective and would
      benefit from Phase 3 trials. No study reported efficacy of biologic medications
      in pediatric patients, however cyclosporine improved clinical severity by the
      greatest amount in this group. LIMITATIONS: A lack of well controlled comparison
      studies make direct comparisons between the treatments difficult. CONCLUSION: For
      treatment of severe AD, the strongest evidence currently exists for dupilumab and
      cyclosporine at improving clinical disease severity. Further research is required
      to determine long term safety and efficacy of biologic medications.

PMID- 30296536
TI  - Achieving eversion utilizing topical tissue adhesive.

PMID- 30296537
TI  - Analysis of cutaneous Merkel Cell Carcinoma outcomes after different surgical
      interventions.
AB  - BACKGROUND: Current guidelines recommend local excision margin (EM) with 1 to 2cm
      on primary merkel cell carcinoma (MCC) site. OBJECTIVE: We compared survival
      outcomes of MCC patients treated with different surgical interventions. METHODS:
      A retrospective analysis of MCC cases in the SEER database was performed by
      Kaplan-Meier, competing risk and Cox proportional hazards regression model
      analyses. Influence of age, T stage, AJCC stage, adjuvant radiotherapy and other
      subgroups were also analyzed by pair-wise log-rank test. RESULTS: Our results
      indicated significant association between local destruction method and inferior
      survival, while EM>2cm showed significantly higher overall survival (OS). In
      addition, competing risk analysis depicted similar trend as Kaplan-Meier
      analysis, and considerably reduced estimated cumulative incidence. Further
      subgroup pair-wise analysis demonstrated that EM>2cm method had better survival
      in patients younger than 60 years, having smaller tumor diameters (T1 and T2) or
      undergone adjuvant radiotherapy (p<0.05). In contrast, different EMs did not show
      any significant association with survival rate in patients older than 75 years or
      stage III tumors. LIMITATIONS: This study was not prospectively randomized
      without relapse data. CONCLUSIONS: It is challenging to make optimal EM
      recommendations, as surgical options may depend on individual case situations.
      Further prospective randomized studies are warranted.

PMID- 30296538
TI  - Co-occurrence of infantile hemangiomas and other birthmarks.

PMID- 30296539
TI  - Comparative Clinicopathological Analysis of Cutaneous Peripheral T-cell lymphoma,
      Not Otherwise Specified, According to Primary Tumor Site.

PMID- 30296540
TI  - Dipeptidyl-peptidase IV inhibitor-associated bullous pemphigoid: A systematic
      review and meta-analysis.

PMID- 30296541
TI  - Future considerations for clinical dermatology in the setting of 21st century
      American policy reform: corporatization and the rise of private equity in
      dermatology.
AB  - Within the last two decades, for-profit financial groups have become increasingly
      involved in health care. Outlier dermatology practices with high volumes of well
      reimbursed procedures are attractive to consolidation backed by private equity.
      With fewer choices for independent or group private practice, junior
      dermatologists are increasingly seeking employment without ownership in private
      equity-backed corporate groups, whose primary fiscal responsibility lies with
      investors. Medicare's response to corporatization and consolidation has already
      changed the practice of dermatopathology. Dermatologists should be aware of this
      history, given the ability of corporations and private equity groups to shape the
      present and future of our field.

PMID- 30296542
TI  - Predictors of mucosal melanoma survival in a population-based setting.
AB  - BACKGROUND: Mucosal melanomas are rare and aggressive neoplasms, with little
      published population-based data on predictors of survival. OBJECTIVE: To assess
      the influences of race/ethnicity, sex, tumor stage, tumor thickness, and anatomic
      site on mucosal melanoma survival estimates. METHODS: We analyzed 132,751 cases
      of melanoma, including 1,824 mucosal melanomas, diagnosed between 1994 and 2015
      and reported to the California Cancer Registry. Kaplan-Meier survival analysis
      and Cox proportional hazards regression assessed the prognostic variables.
      RESULTS: The 5-year relative survival for mucosal melanomas (27.64%, 95%
      confidence interval [CI] 25.42 - 29.91) was significantly lower than for
      cutaneous melanomas (76.28%, 95% CI 76.03 - 76.53). Stage independently
      influenced survival, and thickness did not predict survival for neoplasms of
      known depth. Less common anatomic sites conferred worse prognoses (hazard ratio
      [HR] 1.93, 95% CI: 1.41 - 2.64). LIMITATIONS: Lack of a standardized staging
      system may have resulted in misclassification of stage for some neoplasms. The
      influence of genetics is unknown because our database did not contain genetic
      characteristics. CONCLUSIONS: Stage and anatomic site, but not thickness (i.e.
      Breslow depth), race, or ethnicity, determine prognosis of mucosal melanomas.
      Considering the poor prognosis for all stages of mucosal melanoma, dermatologists
      should incorporate examination of the oropharynx and genitalia in the full body
      skin exam.

PMID- 30296544
TI  - Steroids-specific target library for steroids target prediction.
AB  - Steroids exist universally and play critical roles in various biological
      processes. Identifying potential targets of steroids is of great significance in
      studying their physiological and biochemical activities, the side effects and for
      drug repurposing. Herein, aiming at more precise steroids targets prediction, a
      steroids-specific target library integrating 3325 PDB or homology modeling
      structures categorized into 196 proteins was built by considering chemical
      similarity from DrugBank and biological processes from KEGG. The main properties
      of this library include: (1) It was manually prepared and checked to eliminate
      mistakes. (2) The library enriched the possible steroids targets and could
      decrease the false positives of structure-based target screening for steroids.
      (3) The ranking by protein name instead of PDB ID could make the screening more
      efficiency and precise. (4) Protein flexibility was taken into account partially
      by the different active conformations through the structural redundancy of each
      category of protein, which leads to more accurate prediction. The case studies of
      glycocholic acid and 24-epibrassinolide proved its powerful predictive accuracy.
      In summary, our strategy to build the steroids-specific protein library for
      steroids target prediction is a promising approach and it provides a novel idea
      for the target prediction of small molecules.

PMID- 30296543
TI  - C21 steroids from Streptocaulon juventas (Lour) Merr. induce apoptosis in HepG2.
AB  - Three new C21 steroids, i.e., (3beta,17alpha,20S)-pregn-5(6)-ene-3, 17, 20-triol
      3-O-beta-d-digitalopyranosyl-(1 -> 4)-beta-d-digitalopyranoside (4),
      (3beta,17alpha,20S)-pregn-5(6)-ene-3, 17, 20-triol-20-O-beta-d-glucopyranosyl-(1 
      > 6)-beta-d-glucopyranosyl-(1 -> 2)-beta-d-digital-opyranoside (8), (3beta, 20R)
      pregn-14(15)-ene-3, 20, 21-triol-3-O-beta-d-glucopy-ranoside (10), along with ten
      known C21 steroids were isolated from Streptocaulon juventas. Their structures
      were elucidated on the basis of 1D and 2D NMR spectroscopic techniques, mass
      spectrometry as well as comparison with the literature. All the isolated
      compounds were screened for their in vitro cytotoxicity against human liver
      cancer cells (HepG2) and the structure-activity relationships were also analyzed.
      Moreover, compounds 1-3, 5, 10-12, which displayed cytotoxic activities in HepG2
      cells, were tested for the selective index (SI) by the ratio of cytotoxic effect
      on human hepatocytes (LO2) to that on HepG2. As a result, new compound 10
      exhibited a good inhibitory activity against HepG2 with IC50 value 11.7 MUM as
      well as high SI value 3.5. Furthermore, compound 10 could induce HepG2 cells
      apoptosis by flow cytometry.

PMID- 30296545
TI  - Timosaponin AIII: A novel potential anti-tumor compound from Anemarrhena
      asphodeloides.
AB  - Timosaponin AIII, a major steroidal saponin found in Anemarrhena asphodeloides
      Bge., which has been widely used as anti-pyretic, anti-diabetic, anti
      inflammatory, anti-platelet aggregator and anti-depressant agents in traditional
      Chinese medicine. Recent pharmacological study showed that timosaponin AIII had
      potent cytotoxicity, which was potential to be developed as an anticancer agent,
      however the molecular mechanism underlying the anticancer activity has not been
      fully elucidated. This review aims to give a systematic summary of the study of
      timosaponin AIII to reveal its anti-tumor activities by investigating invasion
      and migration, apoptosis, autophagy and reversing multi-drug resistance.
      Furthermore, we also make an overview of the mechanisms identified till now.
      These meaningful findings may provide novel insights on exploiting timosaponin
      AIII as a new anti-tumor agent.

PMID- 30296546
TI  - Pregn-5-en-3beta-ol and androst-5-en-3beta-ol dicarboxylic acid esters as
      potential therapeutics for NMDA hypofunction: In vitro safety assessment and
      plasma stability.
AB  - Neurosteroids are endogenous steroidal compounds that can modulate neuronal
      receptors. N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated, calcium
      permeable ion channels that are of particular interest, as they participate in
      synaptic transmission and are implicated in various processes, such as learning,
      memory, or long-term neuronal potentiation. Positive allosteric modulators that
      increase the activity of NMDARs may provide a therapeutic aid for patients
      suffering from neuropsychiatric disorders where NMDAR hypofunction is thought to
      be involved, such as intellectual disability, autism spectrum disorder, or
      schizophrenia. We recently described a new class of pregn-5-ene and androst-5-ene
      3beta-dicarboxylic acid hemiesters (2-24) as potent positive modulators of
      NMDARs. Considering the recommended guidelines for the early stage development of
      new, potent compounds, we conducted an in vitro safety assessment and plasma
      stability screening to evaluate their druglikeness. First, compounds were
      screened for their hepatotoxicity and mitochondrial toxicity in a HepG2 cell
      line. Second, toxicity in primary rat postnatal neurons was estimated. Next, the
      ability of compounds 2-24 to cross a Caco-2 monolayer was also studied. Finally,
      rat and human plasma stability screening revealed an unforeseen high stability of
      the C-3 hemiester moiety. In summary, by using potency/efficacy towards NMDARs
      data along with toxicity profile, Caco-2 permeability and plasma stability,
      compounds 14 and 15 were selected for further in vivo animal studies.

PMID- 30296547
TI  - Steroid profiling in nails using liquid chromatography-tandem mass spectrometry.
AB  - The retrospective analysis of endogenous steroid hormones in nails can be used to
      elucidate endocrine diseases and thus help with their diagnosis and treatment. A
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) based method was
      developed for the simultaneous identification and quantification of 12 steroid
      hormones (aldosterone, cortisone, cortisol, corticosterone, 11-deoxycortisol,
      androstenedione, 11-deoxycorticosterone, testosterone, dehydroepiandrosterone
      (DHEA), 17alpha-hydroxyprogesterone (17-OHP), dihydrotestosterone (DHT) and
      progesterone) in human fingernails. Steroid hormones were extracted from 0.5 mg
      to 10 mg pulverized nail clippings by methanolic extraction, followed by a liquid
      liquid extraction. The analysis was conducted with LC-MS/MS in electrospray
      ionization positive mode. The method was validated in terms of linearity, limit
      of detection (LOD), limit of quantification (LOQ), precision, accuracy, matrix
      effect, recovery and robustness. It was successfully applied for steroid
      profiling in nails of mothers and their infants where cortisol, cortisone,
      testosterone, progesterone, androstenedione and 11-deoxycorticosterone could be
      detected. Furthermore, it could be shown that there is no significant difference
      in concentrations between left and right hand for cortisol, cortisone and
      progesterone. A positive linear correlation between cortisol and cortisone in
      nails was found. In conclusion, it could be shown that nails are a suitable
      matrix for the retrospective monitoring of cumulative steroid hormone levels.

PMID- 30296548
TI  - Separation and identification of the epimeric doping agents - Dexamethasone and
      betamethasone in equine urine and plasma: A reversed phase chiral chromatographic
      approach.
AB  - Chirality is one of the most important considerations when controlling doping.
      The epimeric corticosteroids dexamethasone and betamethasone are significantly
      potent and long-acting, and they are highly abused in equestrian sports. The
      scope of this study was to develop a simple and reliable analytical method for
      simultaneously identifying and separating regularly abused co-eluting
      corticosteroids in equine urine and plasma. In this paper, we present a simple
      and rapid method for the chiral separation and identification of epimeric
      mixtures of dexamethasone and betamethasone using a Thermo Q Exactive high
      resolution accurate mass spectrometer. The high resolution accurate mass
      spectrometer system provided extremely high sensitivity, enabling detection of
      each isomer at a very low concentration from complex biological matrices.
      Chromatographic separation was performed using amylose and cellulose chiral
      columns. Reversed phase media showed very good potential for providing a
      successful chiral resolution in LC-MS analysis. This study also focused on
      optimizing the mobile phase for elution strength, nature of the organic modifier,
      additives, and column temperature.

PMID- 30296549
TI  - Fluorine-containing lupane triterpenoid acid derivatives: Design, synthesis and
      biological evaluation as potential anti-inflammatory agents.
AB  - A series of novel fluorine-containing lupane triterpenoid acid derivatives with
      fluoroaromatic amide moieties at the C-28 position (1-8) or with 2
      (fluoroacyl)cyclopentane-1,3-dione fragments at the C-3 position (9-18) of lupane
      skeleton was synthesized. A simple synthesis of novel lupane triterpenoid hybrids
      with 2-(fluoroacyl)-2-cyclopenten-1-one moieties was developed. An interaction of
      2-acyl-3-chlorocyclopent-2-en-1-ones, obtained from corresponding cyclic beta
      triketones, with methyl 3-amino-3-deoxybetulinate gave 3beta-isomers (9-13) and
      3alpha-isomers (14-18) of target hybrids, which were isolated as individual
      compounds. Anti-inflammatory properties of selected synthesized compounds were
      studied in vivo using the histamine-, concanavalin A- and sheep erythrocytes
      immunization-induced mouse paw edema models. The antioxidant activity was
      investigated in vivo on the model of tetracycline-induced hepatitis. Majority of
      synthesized fluorine-containing lupane triterpenoid acid derivatives exhibited
      significant anti-inflammatory and antioxidant effects. Among studied compounds,
      3beta-hybrid 11 with 2-perfluorobutanoyl-2-cyclopenten-1-one moiety was the most
      potent bioactive compound.

PMID- 30296550
TI  - Synthesis and antiproliferative activity of 17-[1',2',3']
      selenadiazolylpregnenolone compounds.
AB  - Using pregnenolone as a starting material, some 3-substituted 17-[1',2',3']
      selenadiazolylpregnenolone derivatives were synthesized, and their structures
      were characterized by IR, NMR and HRMS. The in vitro antitumor activity of the
      compounds was assayed against PC-3,SKOV3,T47D,MCF-7 and HEK293T cell lines. The
      results show that some compounds display selective antiproliferative activity
      against PC-3 and SKOV3 cells lines and are almost inactive to normal kidney
      epithelial cells (HEK293T). The IC50 value are much better than that of
      abiraterone (positive control).

PMID- 30296551
TI  - Peptide-based therapeutics: quality specifications, regulatory considerations,
      and prospects.
AB  - Exquisite selectivity, remarkable efficacy, and minimal toxicity are key
      attributes inherently assigned to peptides, resulting in increased research
      interest from the pharmaceutical industry in peptide-based therapeutics (PbTs).
      Pharmacopoeias develop authoritative standards for PbT by providing standard
      specifications and test methods. Nevertheless, a lack of harmonization in test
      procedures adopted for PbT in the latest editions of Pharmacopoeias has been
      observed. Adoption of a harmonized monograph could increase further the interest
      of the global pharmaceutical industry in PbTs. Here, we provide an overview of
      pharmacopoeial methodologies and specifications commonly observed in PbT
      monographs and highlight the main differences among the pharmacopoeias in terms
      of the active pharmaceutical ingredients that they focus on. We also address the
      prospects for PbTs to mature as a new therapeutic niche.

PMID- 30296552
TI  - Anti-biofilm efficacy of root canal irrigants against in-situ Enterococcus
      faecalis biofilms in root canals, isthmuses and dentinal tubules.
AB  - OBJECTIVE: To investigate the anti-biofilm efficacy of root canal irrigants in
      canal spaces, isthmi and dentinal tubules of root canals ex vivo. METHODS: Fifty
      one single-rooted premolars, each containing an isthmus, were instrumented,
      autoclaved and inoculated with Enterococcus faecalis for 4 weeks. One specimen
      was sectioned for bacteria-specific staining to confirm the presence of biofilms
      using light microscopiy. The remaining specimens were randomly divided to five
      groups: (1) 0.9% NaCl, (2) SilverSol/H2O2, (3) HYBENX, (4) QMix 2 in1, (5) 6%
      NaOCl. Bacterial sampling was performed before (S1) and after (S2) canal
      irrigation. Diluted bacteria suspension was cultured for 48 h for counting the
      colony forming units (CFU). Percentages of dead bacteria and biofilm thickness
      were evaluated by confocal laser scanning microscopy (CLSM). Metabolic activity,
      lactic acid and polysaccharide synthesis of E. faecalis derived from S2 samples
      were analysed. RESULTS: The percentages of dead bacteria were significantly
      affected by the factor "irrigant" (p < 0.001) and the factor "location" (p =
      0.017). The percentages of dead bacteria in the isthmi and canals were both in
      the ordor: NaCl < SilverSol/H2O2 < HYBENX < QMix 2 in1 < NaOCl (p < 0.05). Only
      6% NaOCl disrupted biofilms and significantly reduced their thickness. The CFU,
      metabolic activity, polysaccharide and lactic acid production of E. faecalis were
      all reduced by the disinfecting solutions. CONCLUSIONS: SilverSol/H2O2 and HYBENX
      were less adept than QMix 2 in1 at killing biofilm bacteria in root canals. None
      of these antibacterial irrigants were effective, compared with 6% NaOCl, in
      disrupting biofilms. CLINICAL SIGNIFICANCE: There is advantage in using HYBENX or
      QMix 2 in1 to kill intratubular bacteria biofilms because of their capability in
      removing the inorganic component of the smear layer. SilverSol/H2O2 requires
      extra time to eradicate intratubular biofilms upon removal of the organic and
      inorganic components of the smear layer by other root canal irrigants.

PMID- 30296553
TI  - Silver improves collagen structure and stability at demineralized dentin: A
      dynamic-mechanical and Raman analysis.
AB  - OBJECTIVE: This study aimed to evaluate the effect of silver loaded nanoparticles
      (NPs) application on dentin remineralization. METHODS: Polymethylmetacrylate
      based NPs and silver loaded NPs (Ag-NPs) were applied on demineralized dentin
      surfaces. Dentin was characterized morphologically by scanning electron
      microscopy, mechanically probed by a nanoindenter to test nanohardness and Young
      modulus, and chemically analyzed by Raman spectroscopy after 24 h and 7 d of
      storage. Untreated surfaces were used as control. Data were submitted to ANOVA
      and Student-Newman-Keuls multiple comparisons tests (P < 0.05). RESULTS: After
      Raman analysis, dentin treated with Ag-NPs obtained the lowest mineralization and
      intensity of stoichiometric hydroxyapatite when compared with specimens treated
      with undoped-NPs. The lowest relative mineral concentration, expressed as the
      ratio phosphate or carbonate/phenyl group, and crystallinity was attained by
      dentin treated with Ag-NPs, after 7 d. Ag-NPs application generated the highest
      values of collagen crosslinking (intensity at 1032 cm-1 band). The molecular
      conformation of the collagen's polypeptide chains, amide-I and CH2 also attained
      the highest peaks in dentin treated with Ag-NPs. Staggered and demineralized
      collagen fibrils were observed covering the dentin surfaces treated with Ag-NPs,
      at both 24 h and 7 d. Samples treated with Ag-NPs attained the lowest values of
      nanohardness and Young's modulus at 7 d of storage. CONCLUSIONS: Peritubular and
      intertubular dentin were remineralized when using undoped-NPs. After 7 d,
      collagen treated with NPs was remineralized but dentin treated with Ag-NPs
      attained an improved collagen matrix structure and stability but the lowest
      mineralization and crystallinity. CLINICAL SIGNIFICANCE: Preservation of the
      demineralized organic matrix is fundamental in operative dentistry. Silver
      contributed to improve crosslinking, nature and secondary structure of
      demineralized dentin collagen, for further long-term intrafibrillar
      mineralization.

PMID- 30296554
TI  - Imaging glutamate redistribution after acute N-acetylcysteine administration: A
      simultaneous PET/MR study.
AB  - Glutamate is the most abundant excitatory neurotransmitter in the human brain,
      but in vivo imaging of acute fluctuations in glutamatergic levels has not been
      well established. The purpose of this study was to examine acute changes in
      glutamate after stimulation with N-acetylcysteine (NAC) using a simultaneous
      positron emission tomography/magnetic resonance spectroscopy (PET/MRS) approach.
      Ten healthy adult males were examined in two scanning sessions, and 5g NAC was
      administered 1 h prior to one of the scan sessions. Simultaneous PET/MR data were
      acquired using an integrated 3T PET/MR scanner. Glutamate (Glu), glutamine (Gln),
      and glutamate + glutamine (Glx) levels were assessed from MRS data collected from
      the basal ganglia with PRESS and from the left prefrontal cortex with PRESS and
      MEGAPRESS, and mGluR5 binding (BPND) was assessed from PET data collected with
      [18F]PSS232. NAC administration was associated with a significant reduction in
      Glx and Gln in the basal ganglia spectra, and in Glx in the frontal MEGAPRESS
      spectra (p < 0.05); no differences in [18F]PSS232 BPND were observed with NAC,
      although a correlation between pre-/post-treatment Glx and baseline BPnd was
      found. The MRS-visible Glx signal is sensitive to acute fluctuations in
      glutamate. The change in Glx was mostly driven by a change in Gln, lending weight
      to the notion that Gln can provide a proxy marker for neurotransmitter/synaptic
      glutamate. [18F]PSS232 binding is not sensitive to acute glutamate shifts
      independently, but was associated with the extent of glutamate liberation upon
      NAC stimulation.

PMID- 30296555
TI  - Predominantly global genetic influences on individual white matter tract
      microstructure.
AB  - Individual differences in white matter tract microstructure, measured with
      diffusion tensor imaging (DTI), demonstrate substantial heritability. However, it
      is unclear to what extent this heritability reflects global genetic influences or
      tract-specific genetic influences. The goal of the current study was to quantify
      the proportion of genetic and environmental variance in white matter tracts
      attributable to global versus tract-specific influences. We assessed fractional
      anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial
      diffusivity (RD) across 11 tracts and 22 subdivisions of these tracts in 392
      middle-aged male twins from the Vietnam Era Twin Study of Aging (VETSA). In
      principal component analyses of the 11 white matter tracts, the first component,
      which represents the global signal, explained 50.1% and 62.5% of the variance in
      FA and MD, respectively. Similarly, the first principal component of the 22 tract
      subdivisions explained 38.4% and 47.0% of the variance in FA and MD,
      respectively. Twin modeling revealed that DTI measures of all tracts and
      subdivisions were heritable, and that genetic influences on global FA and MD
      accounted for approximately half of the heritability in the tracts or tract
      subdivisions. Similar results were observed for the AD and RD diffusion metrics.
      These findings underscore the importance of controlling for DTI global signals
      when measuring associations between specific tracts and outcomes such as
      cognitive ability, neurological and psychiatric disorders, and brain aging.

PMID- 30296556
TI  - Ventral striatum links motivational and motor networks during operant-conditioned
      movement in rats.
AB  - Voluntary actions require motives. It is already known that the medial prefrontal
      cortex (MPFC) assess the motivational values. However, it remains unclear how the
      motivational process gains access to the motor execution system in the brain.
      Here we present evidence that the ventral striatum (VS) plays a hub-like role in
      mediating motivational and motor processing in operant behavior. We used positron
      emission tomography (PET) to detect the neural activation areas associated with
      motivational action. Using obtained regions, partial correlation analysis was
      performed to examine how the motivational signals propagate to the motor system.
      The results revealed that VS activity propagated to both MPFC and primary motor
      cortex through the thalamus. Moreover, muscimol injection into the VS suppressed
      the motivational behavior, supporting the idea of representations of motivational
      signals in VS that trigger motivational behavior. These results suggest that the
      VS-thalamic pathway plays a pivotal role for both motivational processing through
      interactions with the MPFC and for motor processing through interactions with the
      motor BG circuits.

PMID- 30296558
TI  - Sex difference in brain CB1 receptor availability in man.
AB  - The endocannabinoid system (ECS) has a widespread neuromodulatory function in the
      central nervous system and is involved in important aspects of brain function
      including brain development, cortical rhythms, plasticity, reward, and stress
      sensitivity. Many of these effects are mediated via the cannabinoid CB1 receptor
      (CB1R) subtype. Animal studies convincingly show an interaction between the ECS
      and sex hormones, as well as a sex difference of higher brain CB1R in males.
      Human in vivo studies of sex difference have yielded discrepant findings. Gender
      differences in CB1R availability were investigated in vivo in 11 male and 11
      female healthy volunteers using a specific CB1R tracer [18F]FMPEP-d2 and positron
      emission tomography (PET). Regional [18F]FMPEP-d2 distribution volume was used as
      a proxy for CB1R availability. In addition, we explored whether CB1R availability
      is linked to neuropsychological functioning. Relative to females, CB1R
      availability was on average 41% higher in males (p = 0.002) with a regionally
      specific effect larger in the posterior cingulate and retrosplenial cortices (p =
      0.001). Inter-subject variability in CB1R availability was similar in both
      groups. Voxel-based analyses revealed an inverse association between CB1R
      availability and visuospatial working memory task performance in both groups (p <
      0.001). A CB1R sex difference with a large effect size was observed and should be
      considered in the design of CB1R-related studies on neuropsychiatric disorders.
      The behavioural correlates and clinical significance of this difference remain to
      be further elucidated, but our studies suggest an association between CB1R
      availability and working memory.

PMID- 30296557
TI  - A neural mechanism of direct and observational conditioning for placebo and
      nocebo responses.
AB  - Classical theories suggest placebo analgesia and nocebo hyperalgesia are based on
      expectation and conditioned experience. Whereas the neural mechanism of how
      expectation modulates placebo and nocebo effects during pain anticipation have
      been extensively studied, little is known about how experience may change brain
      networks to produce placebo and nocebo responses. We investigated the neural
      pathways of direct and observational conditioning for conscious and nonconscious
      conditioned placebo/nocebo effects using magnetoencephalography and a face visual
      cue conditioning model. We found that both direct and observational conditioning
      produced conscious conditioned placebo and nocebo effects and a nonconscious
      conditioned nocebo effect. Alpha band brain connectivity changes before and after
      conditioning could predict the magnitude of conditioned placebo and nocebo
      effects. Particularly, the connectivity between the rostral anterior cingulate
      cortex and middle temporal gyrus was an important indicator for the manipulation
      of placebo and nocebo effects. Our study suggests that conditioning can mediate
      our pain experience by encoding experience and modulating brain networks.

PMID- 30296559
TI  - Time ambiguity during intertemporal decision-making is aversive, impacting choice
      and neural value coding.
AB  - We are often presented with choices that differ in their more immediate versus
      future consequences. Interestingly, in everyday-life, ambiguity about the exact
      timing of such consequences frequently occurs, yet it remains unknown whether and
      how time-ambiguity influences decisions and their underlying neural correlates.
      We developed a novel intertemporal fMRI choice task in which participants make
      choices between sooner-smaller (SS) versus later-larger (LL) monetary rewards
      with systematically varying levels of time-ambiguity. Across trials, delay
      information of the SS, the LL, or both rewards was either exact (e.g., in 5
      weeks), of low ambiguity (4 week range: e.g., in 3-7 weeks), or of high ambiguity
      (8 week range: e.g., in 1-9 weeks). Choice behavior showed that the majority of
      participants preferred options with exact delays over those with ambiguous
      delays, indicating time-ambiguity aversion. Consistent with these results, the
      ventromedial prefrontal cortex showed decreased activation during ambiguous
      versus exact trials. In contrast, intraparietal sulcus activation increased
      during ambiguous versus exact trials. Furthermore, exploratory analyses suggest
      that more time-ambiguity averse participants show more insula and dorsolateral
      prefrontal cortex activation during subjective value (SV)-coding of ambiguous
      versus exact trials. Lastly, the best-fitting computational choice models
      indicate that ambiguity impacts the SV of options via time perception or via an
      additive ambiguity-related penalty term. Together, these results provide the
      first behavioral and neural signatures of time-ambiguity, pointing towards a
      unique profile that is distinct from impatience. Since time-ambiguity is
      ubiquitous in real-life, it likely contributes to shortsighted decisions above
      and beyond delay-discounting.

PMID- 30296560
TI  - Advanced Hadamard-encoded editing of seven low-concentration brain metabolites:
      Principles of HERCULES.
AB  - PURPOSE: To demonstrate the framework of a novel Hadamard-encoded spectral
      editing approach for simultaneously detecting multiple low-concentration brain
      metabolites in vivo at 3T. METHODS: HERCULES (Hadamard Editing Resolves Chemicals
      Using Linear-combination Estimation of Spectra) is a four-step Hadamard-encoded
      editing scheme. 20-ms editing pulses are applied at: (A) 4.58 and 1.9 ppm; (B)
      4.18 and 1.9 ppm; (C) 4.58 ppm; and (D) 4.18 ppm. Edited signals from gamma
      aminobutyric acid (GABA), glutathione (GSH), ascorbate (Asc), N-acetylaspartate
      (NAA), N-acetylaspartylglutamate (NAAG), aspartate (Asp), lactate (Lac), and
      likely 2-hydroxyglutarate (2-HG) are separated with reduced signal overlap into
      distinct Hadamard combinations: (A+B+C+D); (A+B-C-D); and (A-B+C-D). HERCULES
      uses a novel multiplexed linear-combination modeling approach, fitting all three
      Hadamard combinations at the same time, maximizing the amount of information used
      for model parameter estimation, in order to quantify the levels of these
      compounds. Fitting also allows estimation of the levels of total choline (tCho),
      myo-inositol (Ins), glutamate (Glu), and glutamine (Gln). Quantitative HERCULES
      results were compared between two grey- and white-matter-rich brain regions (11
      min acquisition time each) in 10 healthy volunteers. Coefficients of variation
      (CV) of quantified measurements from the HERCULES fitting approach were compared
      against those from a single-spectrum fitting approach, and against estimates from
      short-TE PRESS data. RESULTS: HERCULES successfully segregates overlapping
      resonances into separate Hadamard combinations, allowing for the estimation of
      levels of seven coupled metabolites that would usually require a single 11-min
      editing experiment each. Metabolite levels and CVs agree well with published
      values. CVs of quantified measurements from the multiplexed HERCULES fitting
      approach outperform single-spectrum fitting and short-TE PRESS for most of the
      edited metabolites, performing only slightly to moderately worse than the fitting
      method that gives the lowest CVs for tCho, NAA, NAAG, and Asp. CONCLUSION:
      HERCULES is a new experimental approach with the potential for simultaneous
      editing and multiplexed fitting of up to seven coupled low-concentration and six
      high-concentration metabolites within a single 11-min acquisition at 3T.

PMID- 30296561
TI  - Probabilistic TFCE: A generalized combination of cluster size and voxel intensity
      to increase statistical power.
AB  - The threshold-free cluster enhancement (TFCE) approach integrates cluster
      information into voxel-wise statistical inference to enhance detectability of
      neuroimaging signal. Despite the significantly increased sensitivity, the
      application of TFCE is limited by several factors: (i) generalisation to data
      structures, like brain network connectivity data is not trivial, (ii) TFCE values
      are in an arbitrary unit, therefore, P-values can only be obtained by a
      computationally demanding permutation-test. Here, we introduce a probabilistic
      approach for TFCE (pTFCE), that gives a simple general framework for topology
      based belief boosting. The core of pTFCE is a conditional probability, calculated
      based on Bayes' rule, from the probability of voxel intensity and the threshold
      wise likelihood function of the measured cluster size. In this paper, we provide
      an estimation of these distributions based on Gaussian Random Field theory. The
      conditional probabilities are then aggregated across cluster-forming thresholds
      by a novel incremental aggregation method. pTFCE is validated on simulated and
      real fMRI data. The results suggest that pTFCE is more robust to various ground
      truth shapes and provides a stricter control over cluster "leaking" than TFCE
      and, in many realistic cases, further improves its sensitivity. Correction for
      multiple comparisons can be trivially performed on the enhanced P-values, without
      the need for permutation testing, thus pTFCE is well-suitable for the improvement
      of statistical inference in any neuroimaging workflow. Implementation of pTFCE is
      available at https://spisakt.github.io/pTFCE.

PMID- 30296562
TI  - Pattern-sensitive neurons reveal encoding of complex auditory regularities in the
      rat inferior colliculus.
AB  - A 'pattern alternation paradigm' has been previously used in human ERP recordings
      to investigate the brain encoding of complex auditory regularities, but prior
      studies on regularity encoding in animal models to examine mechanisms of
      adaptation of auditory neuronal responses have used primarily oddball stimulus
      sequences to study stimulus-specific adaptation alone. In order to examine the
      sensitivity of neuronal adaptation to expected and unexpected events embedded in
      a complex sound sequence, we used a similar patterned sequence of sounds. We
      recorded single unit activity and compared neuronal responses in the rat inferior
      colliculus (IC) to sound stimuli conforming to pattern alternation regularity
      with those to stimuli in which occasional sound repetitions violated that
      alternation. Results show that some neurons in the rat inferior colliculus are
      sensitive to the history of patterned stimulation and to violations of patterned
      regularity, demonstrating that there is a population of subcortical neurons,
      located as early as the level of the midbrain, that can detect more complex
      stimulus regularities than previously supposed and that are as sensitive to
      complex statistics as some neurons in primary auditory cortex. Our findings
      indicate that these pattern-sensitive neurons can extract temporal and spectral
      regularities between successive acoustic stimuli. This is important because the
      extraction of regularities from the sound sequences will result in the
      development of expectancies for future sounds and hence, the present results are
      compatible with predictive coding models. Our results demonstrate that some
      collicular neurons, located as early as in the midbrain level, are involved in
      the generation and shaping of prediction errors in ways not previously considered
      and thus, the present findings challenge the prevailing view that perceptual
      organization of sound only emerges at the auditory cortex level.

PMID- 30296563
TI  - Machine learning in neuroimaging: Progress and challenges.

PMID- 30296564
TI  - TCF21 inhibits proliferation and chemoresistance through the AKT pathway in human
      gastric cancer.
AB  - In a previous study, we showed that transcription factor 21 (TCF21) is methylated
      and downregulated in human gastric cancer samples and serves as an independent
      prognostic factor. However, its biological role and potential mechanism in
      gastric cancer cells remain unexplored. In the current study, we examined TCF21
      expression in 6 gastric cancer cell lines. The BGC-823 and SGC-7901 cell lines
      were selected for small interfering RNA and plasmid transfection, respectively.
      The results of the Cell Counting Kit-8 assay demonstrated that TCF21 inhibited
      gastric cancer cell proliferation. Cell cycle analysis suggested that TCF21
      inhibited cell cycle progression in gastric cancer cells. The Matrigel invasion
      assay demonstrated that TCF21 negatively regulated invasion. The cell adhesion
      assay showed that TCF21 increased cell adhesion. Gastric cancer cells were
      treated with cisplatin to explore the role of TCF21 in chemoresistance. Cell
      Counting Kit-8 assay and AnnexinV/propidium iodide analyses showed that TCF21
      overexpression sensitized SGC-7901 cells to cisplatin, whereas its depletion
      reduced sensitivity in BGC-823 cells. JC-1 staining was performed to measure the
      effect of TCF21 on mitochondrial potential. TCF21 downregulated mitochondrial
      membrane potential after treatment with cisplatin. Western blot analysis showed
      that TCF21 overexpression negatively regulated Bcl-xL, phosphorylated
      extracellular signal regulated kinase, and phosphorylated AKT expression and
      induced caspase 3 cleavage. LY294002, an AKT inhibitor, blocked the effect of
      TCF21 on Bcl-xL, caspase 3 and CDDP-induced apoptosis. Nude mice experiments
      demonstrated that TCF21 inhibited gastric cancer growth in vivo. In conclusion,
      our results suggest that TCF21 inhibits gastric cancer growth and chemoresistance
      possibly through the AKT signaling pathway.

PMID- 30296565
TI  - Evolutionary distribution of deoxynucleoside 5-monophosphate N-glycosidase,
      DNPH1.
AB  - Deoxynucleoside 5-monophosphate N-glycosidase, DNPH1 is a member of the
      nucleoside 2-deoxyribosyltransferase (NDT) family. This enzyme catalyzes the
      hydrolysis of deoxynucleoside monophosphates into free nucleobase moieties and 2
      deoxyribose 5-phosphates. The DNPH1 enzymatic activity was first demonstrated in
      rats and then in humans. Subsequently the DNPH1 gene was identified in a variety
      of organisms, mainly in Metazoa. Herein, we demonstrate that despite DNPH1 genes
      being distributed in almost all metazoans, the occurrence of DNPH1genes is
      mosaic. For example, they cannot be found anywhere in the entire clade of
      Sauropsida or anywhere in the whole phyla of Arthropoda and Ctenophora. Even
      among mammals, there are organisms without functional DNPH1 protein (Camelidae
      and most likely Cetacea). By our knowledge, the DNPH1 gene is missing in plants,
      fungi and in majority of protists. Accordingly, the enzyme is apparently not of
      vital importance in all the branches of the Tree of Life. Surprisingly the DNPH1
      gene may be found in archaea as well as in bacteria. This refers to the origin of
      the gene from the period before the archaea branched off from other bacteria. We
      show that the genomic and protein primary structures of DNPH1 are highly
      conserved and any modification in such a structure would result in conversion to
      a pseudogene, which could possibly be eliminated from the genome.

PMID- 30296567
TI  - Chicken GHR antisense transcript regulates its sense transcript in hepatocytes.
AB  - An increasing number of evidences indicated that long noncoding RNAs (LncRNAs)
      regulate a variety of biological progresses via different mechanisms. Our
      previous study had identified a chicken growth hormone receptor (GHR) antisense
      transcript (GHR-AS) which regulated GHR sense transcript (GHR-S) in LMH cells. In
      the present study, roles of GHR-AS and its regulatory mechanism were analyzed in
      chicken hepatocytes. The expression patterns of liver GHR-S, GHR-AS and Let-7b
      ascended with the development of chicken. The hepatocytes proliferation was
      promoted and more cells entered into DNA synthesis (S) phase when GHR-AS was
      overexpressed while the cell proliferation was slowed and fewer cells were in S
      phase when GHR-AS was interfered. Meanwhile, the GHR-S increased when we
      overexpressed GHR-AS while it reduced when GHR-AS was inhibited. The S1 Nuclease
      protection assay indicated that GHR-S and GHR-AS formed RNA duplex via GHR-S 3'
      untranslation regon (3'UTR). In hepatocytes or LMH cells, the half-time of GHR-S
      showed a delayed trend when GHR-AS or GHR-AS 5' untranslation regon (5'UTR) was
      overexpressed. Furthermore, the level of GHR-S can be decreased by Let-7b mimics
      whereas it was partially rescued when co-transfected pGHR-AS or pGHR-AS 5'UTR
      with Let-7b mimics. Based on our findings, GHR-AS affected hepatocytes
      proliferation and improved GHR-S stability possibly by forming RNA duplex between
      GHR-S and GHR-AS, competing with Let-7b.

PMID- 30296566
TI  - Liver kinase B1 induces browning phenotype in 3 T3-L1 adipocytes.
AB  - Induction of brown adipocytes in white adipose tissue is a promising therapy for
      combating human obesity and its associated disorders. Liver kinase B1 (LKB1) is a
      tumor inhibitor and metabolic modulator. Recent data suggest that LKB1 is
      necessary for adipogenesis, but its role in the browning of white adipocytes
      remains unknown. The objective of this study was to reveal the effect of LKB1 on
      browning. In our study, we showed that overexpression of LKB1 in 3 T3-L1
      adipocytes up-regulated the expression of brown adipocyte markers, including
      UCP1, PGC-1alpha, Cidea, and PRDM16, and beige-cell-specific genes, such as CD137
      and Tmem26. It was possible that the expression of UCP1 and other beige markers
      was increased by activation of PPARgamma, resulting in the browning of 3 T3-L1
      preadipocytes. The browning effect was abolished by a PPARgamma inhibitor
      (GW9662). Moreover, these effects were dramatically abrogated by silencing of
      LKB1. Additionally, LKB1 decreased the expression levels of adipogenesis proteins
      (C/EBPalpha and SREBP1) and up-regulated lipid catabolism protein, perilipin
      (PLIN). In summary, the study suggested that LKB1 induces the browning of white
      adipocytes, in addition to promoting lipid metabolism. Therefore, LKB1 may be a
      helpful therapeutic candidate for treating obesity.

PMID- 30296568
TI  - Association of PARK2 promoter polymorphisms and methylation with colorectal
      cancer in North Indian population.
AB  - Different diseases have been associated with PARK2/PACRG overlapping promoter
      polymorphisms (rs2276201 and rs9347683) in the recent past. However association
      of these polymorphisms with cancer remains elusive till date. Thus in this study
      we evaluated association between these polymorphisms and colorectal cancer (CRC)
      incidences among North Indians. Genomic DNA was isolated using venous blood of
      400 unrelated subjects (200 CRC cases and 200 healthy controls) of North Indian
      origin. Both SNPs were genotyped using PCR-RFLP method. Promoter methylation
      status in tumor DNA was checked using MS-PCR. Statistical analysis was performed
      using SPSS-17 software. In-silico predictions for transcription factor binding
      were performed using "PROMO" a freely available online tool. SNP rs2276201 showed
      statistically significant difference (P = 0.047) among cases and controls while
      rs9347683 did not (P = 0.113). The TC genotype (OR: 1.855, 95% CI: 1.021-3.369, P
      = 0.043), CC genotype (OR: 1.617, 95% CI: 1.042-2.510, P = 0.032), TT vs CT+CC
      genetic model (OR: 1.60, P = 0.0158) and allelic model (OR: 1.3931, 95% CI:
      1.0498-1.8485, P = 0.0214) of rs2276201 showed significant risk for CRC. For
      rs9347683 AC genotype (OR: 1.604, 95% CI: 1.019-2.523, P = 0.041) and AA vs AC+CC
      genetic model (OR: 1.57, P = 0.039) showed significant risk. Haplotype CC
      provided significant risk (OR: 1.618, 95% CI: 1.112-2.352, P = 0.011) whereas
      haplotype TA provided significant protection (OR: 0.732, 95% CI: 0.543-0.987, P =
      0.040) against CRC. Promoter methylation was significantly higher in tumor grade
      III + IV (OR: 2.37, P = 0.019), while PARK2 expression was lower in cancer
      tissues compared to normal tissue. Here we provide the first report where PARK2
      promoter SNP's rs2276201 and rs9347683 are shown to be significantly associated
      with the risk of CRC development.

PMID- 30296569
TI  - Association of single-nucleotide polymorphisms of the KEAP1 gene with the risk of
      various human diseases and its functional impact using in silico analysis.
AB  - Keap1, Kelch-like erythroid derived Cap 'n' collar homology (ECH) associated
      protein 1 is a highly redox-sensitive member of the BTB-Kelch substrate adaptor
      protein which acts as a major upstream regulator of Nrf2 (Nuclear factor
      erythroid 2-related factor 2) by Cul3 ubiquitin E3 ligase complex, leading to its
      proteasomal degradation. Oxidative and electrophilic stresses impair the
      structural integrity of Keap1-Cul3 ubiquitin E3 ligase complex resulting in the
      dissociation of Nrf2-Keap1 binding and nuclear accumulation of Nrf2. Studies on
      tissue-specific Keap1 null mutation have demonstrated the important roles of
      Keap1 mediated Nrf2 degradation. An increasing body of evidence suggests that
      loss of functional mutation in Keap1 arbitrates constitutive activation and
      expression of Nrf2 which in turn provokes the chemotherapeutic resistance in
      various diseases. The current review addresses the genetic aspects of KEAP1
      including somatic mutations and in silico functional profiling of human disease
      associated and polymorphic amino acid substitutions.

PMID- 30296570
TI  - Is there life in the meconium? A challenging, burning question.

PMID- 30296571
TI  - Nitrogen excretion during marsupial development in the terrestrial isopod
      Armadillidium vulgare.
AB  - Marsupial embryos of Armadillidium vulgare (Isopoda: Oniscidea) were collected at
      different stages of development and assayed for products of nitrogen excretion.
      Stages were classified as early stage one, late stage one (clear embryo and
      somite differentiation), early stage two (chorion shed, prior to blastokinesis),
      late stage two (following blastokinesis), and mancae (vitelline membrane shed;
      second embryonic molt). Stage one and stage two embryos were primarily
      ammonotelic. Mancae showed a significant increase in stored uric acid and
      decrease in ammonia production, in most cases to undetectable levels. The
      increased metabolic rate of mancae, and the fact that they imbibe marsupial fluid
      prior to exiting the marsupium, may have favored a switch from ammonotely to
      uricotely to avoid ammonia toxicity. Protein metabolism, estimated from ammonia
      production, accounted for 7% of the measured catabolic rate in Stage 2 embryos.
      Newly emerged juveniles showed a >2-fold increase in metabolism relative to
      mancae, accompanying the transition from aquatic to aerial respiration. Following
      48 h post-emergence, juveniles resumed ammonia excretion, volatilizing the base
      (NH3) as in later instars. Elevated ammonia excretion in early juveniles may
      derive from the catabolism of remaining yolk protein. A sharp increase in whole
      animal glutamine in juveniles is consistent with its role as an intermediary
      nitrogen store during periodic ammonia excretion. Total ammonia concentration in
      the marsupial fluid fluctuated but did not increase significantly over time and
      ammonia was not volatilized across the oostegites, indicating that embryo ammonia
      is transported into the maternal hemolymph for excretion.

PMID- 30296572
TI  - Development of a safety and efficacy nanoemulsion delivery system encapsulated
      gambogic acid for acute myeloid leukemia in vitro and in vivo.
AB  - This study aimed to improve the solubility, reduce the side effects and enhance
      the efficacy of gambogic acid against acute myeloid leukemia in vitro and in
      vivo. This oil-in-water nanoemulsion (average size 17.20 +/- 0.11 nm, zeta
      potential 4.17 +/- 0.82 mV) containing Tween-80, glycol, squalene and gambogic
      acid with improving 4000 times solubility was prepared by pseudoternary phase
      diagrams. We found that this nanoemulsion successfully encapsulated gambogic
      acid; it was stable and showed an obvious delayed release effect for the drug in
      three different phosphate-buffered saline (pH = 2.0, 5.8 and 7.4). The half
      inhibiting concentration (IC50) of this nanoemulsion (480.7 MUg/mL and 408
      MUg/mL) were 1.67 times and 1.98 times higher than those of its water solution
      (287 MUg/mL and 206 MUg/mL) after acting on the toxicity standard cell line (L929
      line) for 24 h and 48 h, respectively. Importantly, acute injection toxicity
      indicated that the half lethal dose (LD50) of this nanoemulsion (23.25 mg/kg, 95%
      LD50, 21.7-25.16 mg/kg) was 1.26 times higher than that of its water solution
      (18.59 mg/kg, 95% LD50, 16.84-20.53 mg/kg). Compared with its suspension, the
      bioavailability of this nanoemulsion was 318.2%. Furthermore, this nanoemulsion
      had a better efficacy against the acute myeloid leukemia in vitro and in vivo by
      improving the time and percent of survival (MV4-11 engrafts mice) and reducing
      half inhibiting concentration values in acute myeloid leukemia such as Jurket, HL
      60 and MV4-11 cells. Our studies suggested that this nanoemulsion may be a
      promising therapeutic medicine for acute myeloid leukemia.

PMID- 30296574
TI  - Evaluating the frequency of operational research conducted during the 2014-2016
      West Africa Ebola epidemic.
AB  - INTRODUCTION: The West Africa Ebola epidemic of 2014-2016 was the largest Ebola
      outbreak on record, and thousands of individuals were involved in the response,
      including local and national governments, as well as numerous philanthropic and
      other non-governmental organizations. A number of after-action reports and other
      reviews of the global response to the epidemic routinely pointed out key
      challenges, including gaps in operational research. METHODS: To determine the
      extent to which operational research studies were conducted during the 2014-2016
      West Africa Ebola epidemic, a quantitative analysis of the literature published
      during and immediately after the epidemic was conducted. The goal was to identify
      the proportion of all Ebola-related publications released regarding the epidemic
      that addressed operational aspects of the response. It was also sought to
      describe, at a general level, the sorts of studies that were published during the
      epidemic, with the goal of increasing understanding of whether additional efforts
      are needed to encourage the conduct and dissemination of operational studies
      during future public health crises. RESULTS: Among the 3681 publications on Ebola
      published between the World Health Organization announcement of the Ebola
      outbreak in March 2014 and the end of 2017, 109 (3%) were determined to be
      operational research publications. Among these, 64 (58%) were published after the
      World Health Organization initially declared the outbreak over on January 14,
      2016, reflecting the time delay of sharing operational lessons with the broader
      preparedness and response community. DISCUSSION: Improved sharing of firsthand,
      operational knowledge from practitioners who respond to outbreaks is critical for
      improving preparedness activities and informing the development of sound,
      effective policies that support ongoing and future preparedness efforts. Based on
      the results from this review, we propose several policy and programmatic
      innovations that could facilitate knowledge sharing during future outbreaks.

PMID- 30296573
TI  - Investigation of the risk factors associated with the failure of hepatitis B
      vaccination of neonates in Yunnan province, China.
AB  - OBJECTIVE: This study aimed to investigate HBsAg positive rates and risk factors
      of HBV infection among the children less than 15 years old in Yunnan province, a
      remote southwest part of mainland China. METHODS: Multi-stage sampling was used
      to randomly select study subjects from 9,360,000 individuals. Hepatitis B vaccine
      inoculation rate and HBsAg positive rate were investigated, and then propensity
      score and generalized linear mixed model (GLMMs) were applied to the case-control
      study. RESULTS: The average HBsAg positive rate was 1.81%, with 1.2% in urban
      areas and 2.4% in rural areas. Rate of first-dose-in-time in urban areas was
      77.7%, obviously higher than 49.5% in rural areas (chi2=2811.71, P<0.01).
      Similarly, 3-dose completion coverage rate in urban areas was 93.7%, also higher
      than 79.0% in rural areas (chi2=1561.43, P<0.01). Maternal HBeAg positivity and
      HBsAg positivity were proved to be the main risk factors of children with HBV
      infection. Moreover, paternal HBeAg positivity, paternal HBsAg positivity, the
      absence and unknown status of HBV vaccine inoculation were risk factors of
      children with HBV infection as well. CONCLUSION: It was very important to improve
      the HBV vaccine inoculation rates. Delivering babies in hospital and timely
      inoculation with HBV vaccine were efficient ways to prevent HBV vertical
      transmission.

PMID- 30296575
TI  - Postoperative complications in adult spinal deformity patients with a mental
      illness undergoing reconstructive thoracic or thoracolumbar spine surgery.
AB  - BACKGROUND CONTEXT: Previous studies have found an association between mental
      illness and poor outcomes in spine surgery, but little is known about the effects
      of depression and/or anxiety on the adult spinal deformity population. In
      addition, most relevant studies exclusively focused on the lumbar spine and had
      relatively small patient sizes. PURPOSE: The aim of this study was to investigate
      whether adult spinal deformity patients with depression and/or anxiety have an
      increased risk of postoperative complications and reoperation following posterior
      thoracolumbar spinal surgery. STUDY DESIGN/SETTING: Retrospective database study.
      METHODS: Adult patients (over 18 years of age) with a diagnosis of spinal
      deformity undergoing any reconstructive thoracic or thoracolumbar spinal
      procedure with a posterior approach between 2007 and 2015 Q2 were identified
      using Current Procedural Terminology codes to query the Pearl Diver patient
      record database (Pearl Diver Technologies, West Conshohocken, PA, USA). The
      database includes records of approximately 18 million patients across the United
      States having Humana insurance. Further selection of patients with depression
      and/or anxiety and their associated postoperative complications were identified
      using ICD-9 and ICD-10 diagnosis codes (International Classification of Diseases
      9th-10th edition). The mental illness cohort was matched to a control group
      according to age, sex, and Charlson Comorbidity Index. Patient data was analyzed
      for reoperation rates and incidence of common postoperative complications.
      RESULTS: Multilevel posterolateral fusion was the most common included posterior
      thoracic reconstructive surgery. The mental illness cohort (n = 327) had
      significantly increased rates of infection (odds ratio [OR] = 1.743, p = .022)
      and respiratory complications (OR = 1.492, p = .02) at the 90-day postoperative
      period. The rates of incision and drainage (OR = 1.379, p = .475) and pneumonia
      (OR = 1.22, p = .573) were increased in the mental illness cohort at the 90-day
      postoperative period, but not significantly. There were no significant
      differences in complication and reoperation rates at 1-year postoperatively.
      CONCLUSIONS: Patients with spinal deformity and pre-existing depression and/or
      anxiety treated with a posterior thoracolumbar reconstructive spinal surgery had
      significantly elevated risk of postoperative infections and respiratory
      complications when compared with the control group.

PMID- 30296576
TI  - Patient-reported outcomes unbiased by length of follow-up after lumbar
      degenerative spine surgery: Do we need 2 years of follow-up?
AB  - BACKGROUND: In modern clinical research, the accepted minimum follow-up for
      patient-reported outcome measures (PROMs) after lumbar spine surgery is 24
      months, particularly after fusion. Recently, this minimum requirement has been
      called into question. PURPOSE: We aim to quantify the concordance of 1- and 2
      year PROMs to evaluate the importance of long-term follow-up after elective
      lumbar spine surgery. STUDY DESIGN: Retrospective analysis of data from a
      prospective registry. PATIENT SAMPLE: We identified all patients in our
      prospective institutional registry who underwent degenerative lumbar spine
      surgery with complete baseline, 12-month, and 24-month follow-up for ODI and
      numeric rating scales for back and leg pain (NRS-BP and NRS-LP). OUTCOME
      MEASURES: Oswestry Disability Index (ODI) and NRS-BP and NRS-LP at 1 year and at
      2 years. METHODS: We evaluated concordance of 1- and 2-year change scores by
      means of Pearson's product-moment correlation and performed logistic regression
      to assess if achieving the minimum clinically important difference (MCID) at 12
      months predicted 24-month MCID. Odds ratios (OR) and their 95% confidence
      intervals (CI), as well as model areas-under-the-curve were obtained. RESULTS: A
      total of 210 patients were included. We observed excellent correlation among 12-
      and 24-month ODI (r = 0.88), NRS-LP (r = 0.76) and NRS-BP (r = 0.72, all p
      <.001). Equal results were obtained when stratifying for discectomy,
      decompression, or fusion. Patients achieving 12-month MCID were likely to achieve
      24-month MCID for ODI (OR: 3.3, 95% CI: 2.4-4.1), NRS-LP (OR: 2.99, 95% CI: 2.2
      4.2) and NRS-BP (OR: 3.4, 95% CI: 2.7-4.2, all p <.001) with excellent areas
      under-the-curve values of 0.81, 0.77, and 0.84, respectively. Concordance rates
      between MCID at both follow-ups were 87.2%, 83.8%, and 84.2%. A post-hoc power
      analysis demonstrated sufficient statistical power. CONCLUSIONS: Irrespective of
      the surgical procedure, 12-month PROMs for functional disability and pain
      severity accurately reflect those at 24 months. In support of previous
      literature, our results suggest that 12 months of follow-up may be sufficient for
      evaluating spinal patient care in clinical practice as well as in research.

PMID- 30296577
TI  - The impact of surgical reduction of high-grade lumbosacral spondylolisthesis on
      proximal femoral angle and qualityof life.
AB  - BACKGOUND CONTEXT: Abnormal proximal femoral angle (PFA) was recently found to be
      associated with deteriorating sagittal balance and quality of life (QoL) in high
      grade spondylolisthesis (HGS). However, the influence of PFA on the QoL of
      patients undergoing surgery remains unknown. PURPOSE: This study compares the pre
      and postoperative measurements of sagittal balance including PFA in patients
      with lumbosacral HGS after surgery. It also determines if PFA is a radiographic
      parameter that is associated with QoL in patients undergoing surgery. STUDY
      DESIGN: Retrospective cohort study. PATIENT SAMPLE: Thirty-three patients (mean
      age 15.6 +/- 3.0 years) operated for L5-S1 HGS between July 2002 and April 2015.
      Thirteen had in situ fusion and 20 had reduction to a low-grade slip. OUTCOME
      MEASURES: The outcome measures included PFA and QoL scores measured from the
      Scoliosis Research Society SRS-30 QoL questionnaire. METHODS: The minimum follow
      up was 2 years. PFA and QoL were compared pre- and postoperatively. Statistical
      analysis used nonparametric Mann-Whitney and Wilcoxon Signed Rank tests, Chi
      square tests to compare proportions, and bivariate correlations with Spearman's
      coefficients. RESULTS: A decreasing PFA correlated with less pain (r = -0.56, p =
      .010), improved function (r = -0.51, p = .022) and better self-image (r = -0.46,
      p = .044) postreduction. Reduction decreased PFA by 5.1 degrees  (p = .002),
      whereas in situ fusion did not alter PFA significantly. Patients with normal
      preoperative PFA had similar postoperative QoL regardless of the type of surgery,
      except for self-image, which improved further with reduction (3.73 +/- 0.49 to
      4.26 +/- 0.58, p = .015). Patients with abnormal preoperative PFA tended to have
      a higher QoL in all domains after reduction. CONCLUSION: Decreasing PFA
      correlates with less pain, better function and self-image. Reduction of HGS
      decreases PFA. Reduction also relates to a better postoperative QoL when the
      preoperative PFA is abnormal. When the preoperative PFA is normal, in situ fusion
      is equivalent to reduction except for self-image, which is better improved after
      reduction.

PMID- 30296578
TI  - Cochlear connexin 30 homomeric and heteromeric channels exhibit distinct assembly
      mechanisms.
AB  - Many of the mutations in GJB2 and GJB6, which encode connexins 26 and 30 (Cx26
      and Cx30), impair the formation of membrane channels and cause autosomal
      syndromic and non-syndromic hearing loss. In cochlear non-sensory supporting
      cells, Cx26 and Cx30 form two types of homomeric and heteromeric gap junctions.
      The biogenesis processes of these channels occurring in situ remain largely
      unknown. Here we show that Cx30 homomeric and Cx26/Cx30 heteromeric gap junctions
      exhibit distinct assembly mechanisms in the cochlea. When expressed as homomeric
      channels, Cx30 preferentially interacts with beta-actin in the peripheral non
      junctional membrane region, called perinexus, and strongly relies on the actin
      network for gap junction plaque assembly. In contrast, we found that Cx26/Cx30
      heteromeric gap junction plaques are devoid of perinexus and associated actin
      network, and resist to actin-depolymerizating drug. This supports that Cx26/Cx30
      oligomers could be directly delivered from the interior of the cell to the
      junctional plaque. Altogether, our data provide a novel insight in homomeric and
      heteromeric gap junction plaque assembly in the cochlea.

PMID- 30296579
TI  - Protective effects of isatin and its synthetic derivatives against iron, copper
      and lead toxicity.
AB  - INTRODUCTION: While some metals are required for physiological functions in the
      form of essential trace elements, they can cause toxicity in the excessive
      concentrations. Chelation therapy was used to reduce the adverse effects of acute
      and chronic poisoning by metals. Isatin derivatives form complexes with copper
      ions indicating that they may have protective activity against metal overload.
      METHOD: In this study, four compounds (isatin and three isatin-derivatives Mj1,
      TR and Mk1) were evaluated for drug-likeliness. Then their potency inhibiting
      cell proliferation was determined in HEK293 cell culture assay. Finally, IC50
      values for lead, copper, and iron was evaluated in the absence and also the
      presence of isatin and its derivatives. RESULTS: Isatin and its derivatives used
      in this study complied with the Lipinski criteria for drug-likeliness. The
      greatest difference between the IC50 values and the non-toxic dose was obtained
      for TR and Mj1, respectively. Pretreatment with the Mj1 increased the IC50 values
      for lead, iron, and copper, by 2.1, 1.7 and 1.7 times, respectively. At non-toxic
      dose, TR has only increased the IC50 values for lead and copper by 1.4 and 1.3
      times without affecting iron cytotoxicity. Mk1 increased the IC50 values for
      lead, copper, and iron by 1.3, 1.8 and 1.7 times, respectively. CONCLUSIONS: Mj1
      is suggested as a lead compound for developing therapeutic agents for lead (Pb)
      toxicity and Mk1 for copper and iron.

PMID- 30296580
TI  - Genetic Diversity of Streptococcus pneumoniae in Tunisia.
AB  - OBJECTIVE: The objective of this study was to explore the genetic diversity of
      Streptococcus pneumoniae by using antibiotic susceptibility testing, serotyping
      and multilocus sequence typing (MLST) in a Tunisian pneumology hospital.
      MATERIALS AND METHODS: We investigated 141 strains of S.pneumoniae isolated
      between 2009 and 2016 in the Microbiology Laboratory at Pneumology Hospital A.
      Mami, Tunisia. Antimicrobial susceptibility was tested using the disk diffusion
      method. The MICs of penicillin G, amoxicillin, and cefotaxime were determined by
      E-test. Serotyping was inferred from the results of a multiplex PCR method
      targeting forty serotypes. Sequence types (ST) of S.pneumoniae isolates were
      determined using MLST technique. RESULTS: Among the 141 S. pneumoniae, 69.5% were
      resistant to erythromycin. The evaluation of susceptibility to beta-lactams
      showed that 63.8% of the strains were non-susceptible to penicillin, 34% had
      decreased susceptibility to amoxicillin, and 15% to cefotaxime. We detected 25
      serotypes and 10 isolates that were classified as non-typable. The vaccine
      coverage was 57%, 60.3% and 75.1% for pneumococcal conjugate vaccine 7 (PCV7),
      PCV10, and PCV13 serotypes, respectively. Overall, 73 STs were identified in this
      study including 23 that were described for the first time. The most frequent STs
      were ST179 (n=17), ST3772 (n=14), ST2918 (n=10), ST4003 (n=5) and were related to
      serotypes 19F, 19A, 14 and 23F, respectively. We classified 110 strains within 45
      STs. Three international antibiotic-resistant clones were found, Denmark14-ST230
      (n=22), Spain9V-ST156 (n=22) and Portugal19F-ST177 (n=20). CONCLUSION: This study
      emphasizes the clonal and international dissemination of antibiotic-resistant
      clones of S.pneumoniae. Significant differences in genetic variation were
      documented by MLST, within the various serotypes identified.

PMID- 30296581
TI  - Plasma and interstitial fluid population pharmacokinetics of vancomycin in
      critically patients with sepsis.
AB  - OBJECTIVES: Vancomycin is a commonly prescribed antibiotic in the intensive care
      unit (ICU). However, there is limited data describing its distribution into the
      interstitial space fluid (ISF) of tissues. The aim of this study was to describe
      the plasma and tissue ISF population pharmacokinetics of vancomycin in critically
      ill patients with sepsis. METHODS: Serial vancomycin blood and ISF samples were
      collected at pre-specified time intervals in critically ill patients with sepsis.
      ISF sampling occurred using a subcutaneously inserted microdialysis catheter.
      Bioanalysis was undertaken using a validated spectrometric assay method.
      Population pharmacokinetic analysis was performed using Pmetrics(r). RESULTS:
      Seven patients were recruited and pharmacokinetic data was available for six. The
      median (IQR) age, weight, Acute Physiological and Chronic Health Evaluation II
      score, Sequential Organ Failure Assessment score and measured creatinine
      clearance (CrCL) were 55 (44-67) years, 85 (81-102) kg, 20 (16-29), 5 (4-8), and
      90 (83-98) mL/min respectively. Vancomycin pharmacokinetics were best described
      by a three-compartment linear model. Measured CrCL (on vancomycin clearance) and
      weight (on volume of distribution of the central compartment, Vc) were the only
      patient covariates that improved the model fit. The coefficients of variation for
      the vancomycin rate constants into and out of the peripheral and tissue ISF
      compartments were also high, ranging from 47% to 134%. CONCLUSIONS: There is
      significant variability of vancomycin distribution into tissue ISF which we were
      not able to explain with patient characteristics.

PMID- 30296582
TI  - First Hospitalization for Heart Failure in Outpatients With Stable Coronary
      Artery Disease: Determinants, Role of Incident Myocardial Infarction, and
      Prognosis.
AB  - BACKGROUND: We lack recent data on the incidence, correlates, and prognosis
      associated with heart failure (HF) development in patients with stable coronary
      artery disease (CAD). Here, we analyzed HF development in a contemporary
      population of outpatients with stable CAD. METHODS AND RESULTS: Of 4184
      unselected outpatients with stable CAD (ie, myocardial infarction [MI] and/or
      coronary revascularization >1 year earlier) included in the multicenter CORONOR
      registry, we identified 3871 patients with no history of hospitalization for HF
      at inclusion and followed 3785 (98%) of them for 5 years. During follow-up, 211
      patients were hospitalized for HF (5-year cumulative incidence 5.7%) and 163
      patients had incident MIs. Independent predictors of hospitalization for HF were
      older age, lower left ventricular ejection fraction (LVEF), atrial fibrillation,
      higher body mass index, diabetes mellitus, history of hypertension, angina at
      inclusion, and multivessel CAD. Most hospitalizations for HF (62.6%) occurred in
      patients with LVEF >=50% at inclusion, and most (92.4%) were not preceded by an
      incident MI. Hospitalization for HF was a powerful predictor of mortality
      (adjusted hazard ratio 5.97, 95% confidence interval 4.55-7.83; P < .0001). After
      hospitalization for HF, mortality rates were similar in patients with LVEFs >=50%
      and <50% at hospitalization. CONCLUSIONS: Outpatients with stable CAD were
      frequently hospitalized for HF, and HF was associated with high mortality. Most
      HF hospitalizations were associated with preserved LVEF at inclusion and were not
      preceded by an incident MI.

PMID- 30296583
TI  - Heart Failure Differentially Modulates the Effects of Ivabradine on the
      Electrical Activity of the Sinoatrial Node and Pulmonary Veins.
AB  - BACKGROUND: Ivabradine increases the risk of atrial fibrillation (AF). Heart
      failure (HF) or sinoatrial node (SAN) dysfunction increases the risk of AF, and
      pulmonary veins (PVs) play a critical role in the pathophysiology of AF. This
      study investigated the electrophysiologic effects of ivabradine on SANs and PVs
      in a rabbit model of HF. METHODS AND RESULTS: Conventional microelectrodes were
      used to simultaneously record the electrical activities and conduction properties
      of control and HF rabbit SAN-PV preparations before and after perfusion with
      ivabradine (0.1, 1, or 10 MUmol/L), either alone or with isoproterenol (1
      MUmol/L). HF SANs exhibited a lower beating rate than the control SANs. SAN
      automaticity exit blocks and SAN-PV conduction blocks were observed in 25% and
      50% of samples, respectively, with P < .05 for HF SANs (n = 8) but not for
      control SANs (n = 6). Delayed afterdepolarization (DAD) was observed in 37.5% of
      HF PVs but not in control PVs. HF PVs exhibited a faster beating rate and more
      severe fibrosis than control PVs. Ivabradine reduced the SAN beating rates and
      increased the occurrences of SAN-PV conduction blocks and PV DADs in control and
      HF preparations. However, ivabradine induced SAN automaticity exit blocks only in
      HF preparations. Isoproterenol induced PV burst firing and shifting electrical
      conduction in control and HF preparations. A combination of isoproterenol and
      ivabradine (10 MUmol/L) in HF preparations resulted in the highest incidences of
      PV burst firing and SAN-PV electrical shifting. CONCLUSIONS: HF differentially
      modulates the effects of ivabradine on the electrical activities of SAN and PVs,
      which may increase PV arrhythmogenesis and contribute to the risk of AF in HF
      patients.

PMID- 30296584
TI  - Biochemical Determinants of Changes in Plasma Volume After Decongestion Therapy
      for Worsening Heart Failure.
AB  - BACKGROUND: Optimal vascular volume is required to avoid organ dysfunction during
      decongestive therapy for worsening heart failure (HF). This study investigated
      the relation between changes in serum substance(s) and the vascular volume after
      diuresis in HF patients. METHODS AND RESULTS: Data from 47 patients with HF
      undergoing conventional diuretic therapy were analyzed. Blood tests included
      measurements of hemoglobin, hematocrit, and serum albumin/solutes. The relative
      changes in the plasma volume (%PV) from worsening HF to recovery were determined
      with the use of the Strauss formula. When divided into 2 groups based on the
      median %PV, the group with preserved volume (%PV >= -10%, range -10% to 21%; n =
      23) exhibited a smaller decrease in body weight (-2.50 +/- 1.98 vs -4.29 +/- 2.60
      kg; P = .012) and serum sodium (Na) (-1.57 +/- 3.29 vs -4.13 +/- 4.96 mEq/L; P =
      .04) and chloride (Cl) (-2.0 +/- 4.06 vs -6.79 +/- 5.21 mEq/L; P = .001)
      concentrations and a smaller increase in albumin (0.20 +/- 0.28 vs 0.41 +/-
      0.24g/dL; P = .009) compared with the group with nonpreserved volume (%PV < -11%,
      range -33% to -11%; n = 24) after decongestive therapy. Changes in %PV were
      positively correlated with changes in body weight (r = 0.406; P = .0047) and
      serum Na (r = 0.433; P = .0024) and Cl (r = 0.408; P = .0044) concentrations and
      negatively correlated with changes in albumin (r = -0.492; P = .0004), blood urea
      nitrogen (r = -0.306; P = .037), and creatinine (r = -0.306; P = .036).
      Multivariate logistic regression analysis demonstrated an independent association
      between preserved %PV and an increased or preserved serum Cl concentration after
      decongestive therapy (odds ratio 8.71, 95% confidence interval 1.20-63.0; P =
      .032). CONCLUSIONS: Positive and independent association exists between change in
      the vascular volume and the serum Cl concentration under decongestive HF therapy.

PMID- 30296586
TI  - Laboratory trend in vitamin D status in Ireland: Dual concerns about low and high
      25OHD.
AB  - Serum 25-hydroxyvitamin D (25OHD) is the pre-eminent estimate of vitamin D status
      that we have been measuring in a hospital laboratory setting since the 1970s. We
      previously evaluated the trend in 25OHD results in our laboratory from 1993 to
      2013. Using a time series analysis of monthly average 25OHD results the trend was
      modelled, and this was used to forecast monthly average 25OHD from 2014 to 2016.
      In this study, all 25OHD results from 2014 to 2016 were retrieved (n = 67,922)
      and trimmed to 40,307 results after duplicates were excluded. The average monthly
      actual 25OHD was almost identical to the average monthly forecast 25OHD (p =
      0.028) with a strong correlation between the actual 25OHD and forecast 25OHD (r =
      0.69, p < 0.001). This upward trend is attributed to higher oral intake of
      vitamin D. We have a dual concern: policies to prevent hypovitaminosis D must be
      offset by strategies to avert hypervitaminosis D.

PMID- 30296585
TI  - Proteomics analysis reveals that nitric oxide regulates photosynthesis of maize
      seedlings under water deficiency.
AB  - Nitric oxide (NO) is an important bioactive molecule that functions in regulating
      diverse abiotic stresses in plants, whereas its molecular mechanism remains
      obscure. In this study, treatment with 0.1 mM NO donor (sodium nitroprusside,
      SNP) significantly alleviated the inhibited growth induced by 15%
      polyethyleneglycol (PEG)-stimulated water deficiency (WD) for 3 days in maize
      seedlings, manifested by less decreased plant total fresh weight and dry weight.
      Comprehensive proteome analysis was further used to measure the expression
      profiles of leaf proteins of SNP-pretreated maize seedlings under WD conditions
      to explore the molecular mechanisms of NO-induced WD tolerance. Using 2-DE
      method, 135 protein spots showed significantly enhanced or reduced abundance, of
      which 102 spots were successfully identified MALDI-TOF/TOF MS. The identified
      protein species were associated with diverse functions, and most (52/83, 62.7%)
      of known protein species were related to photosynthetic processes. Compared to
      alone PEG treatment, the abundance of 25 identified protein species in SNP + PEG
      treatment were enhanced among the identified photosynthesis-related protein
      species. In addition, exogenous SNP application dramatically regulated
      chlorophyll alpha fluorescence kinetics e.g. the increase of maximum quantum
      yield of PSII (Fv/Fm), photosynthetic performance index (PI), and IP phase,
      whereas it remarkably reduced the polyphasic OJIP fluorescence transient, the
      accumulation of reactive oxygen species (H2O2 and O2*-) and malondialdehyde
      (MDA). These findings suggest that the NO-induced WD tolerance could be
      associated with improved photosynthetic capability in higher plants.

PMID- 30296587
TI  - Vitamin D C3-epimer levels are proportionally higher with oral vitamin D
      supplementation compared to ultraviolet irradiation of skin in mice but not
      humans.
AB  - A proportion of circulating 25-hydroxy vitamin D3 (25(OH)D3)) undergoes
      epimerization to form C3-epi 25(OH)D3 and C3-epi 1,25(OH)2D3. These epimers have
      less calcaemic activity than non-epimerized metabolites and are not
      differentiated by many immunoassays when reporting total 25(OH)D3 levels. This
      study aimed to compare the effect of exposure to ultraviolet radiation (UVR) and
      oral vitamin D3 supplementation on vitamin D C3-epimer levels. C57Bl/6 female
      mice were fed either vitamin D-sufficient (vitamin D3 2000 IU/kg) or -deficient
      diets (no vitamin D3) for 4 weeks. Among the vitamin D-deficient group, the
      shaved backs of half were irradiated daily for 4 days with 1 kJ/m2 UVR, followed
      by twice weekly irradiation for 4 weeks. Despite similar 25(OH)D3 levels, the UV
      irradiated group had a lower proportion of C3-epi 25(OH)D3 at week 7 (p < 0.05)
      and week 9 (p < 0.01). C3-epimer concentrations and %C3-epi 25(OH)D3 were also
      analysed in serum samples from two human clinical trials. These trials
      investigated the effect of high dose oral vitamin D3 supplementation and
      narrowband UVB phototherapy, respectively. Serum 25(OH)D3 and the %C3-epi
      25(OH)D3 levels measured at 12 months after oral vitamin D3 supplementation were
      not significantly different to those measured at the time of maximal effect of
      phototherapy (2 months). Thus, the proportion of 25(OH)D3 that undergoes
      epimerization is greater with oral vitamin D3 supplementation than exposure to
      UVR in mice, but not in humans. This important difference between human and
      murine vitamin D metabolism warrants consideration when interpreting animal
      studies.

PMID- 30296588
TI  - Screening for Regulatory Variants in 460 kb Encompassing the CFTR Locus in Cystic
      Fibrosis Patients.
AB  - It is estimated that up to 5% of cystic fibrosis transmembrane conductance
      regulator (CFTR) pathogenic alleles are unidentified. Some of these errors may
      lie in noncoding regions of the locus and affect gene expression. To identify
      regulatory element variants in the CFTR locus, SureSelect-targeted enrichment of
      460 kb encompassing the gene was optimized to deep sequence genomic DNA from 80
      CF patients with an unequivocal clinical diagnosis but only one or no CFTR-coding
      region pathogenic variants. Bioinformatics tools were used to identify sequence
      variants and predict their impact, which were then assayed in transient reporter
      gene luciferase assays. The effect of five variants in the CFTR promoter and four
      in an intestinal enhancer of the gene were assayed in relevant cell lines. The
      initial analysis of sequence data revealed previously known CF-causing variants,
      validating the robustness of the SureSelect design, and showed that 85 of 160 CF
      alleles were undefined. Of a total 1737 variants revealed across the extended 460
      kb CFTR locus, 51 map to known CFTR cis-regulatory elements, and many of these
      are predicted to alter transcription factor occupancy. Four promoter variants and
      all those in the intestinal enhancer significantly repress reporter gene
      activity. These data suggest that CFTR regulatory elements may harbor novel CF
      disease-causing variants that warrant further investigation, both for genetic
      screening protocols and functional assays.

PMID- 30296589
TI  - An Optimized Workflow to Evaluate Estrogen Receptor Gene Mutations in Small
      Amounts of Cell-Free DNA.
AB  - The detection of mutated genes in cell-free DNA (cfDNA) in plasma has emerged as
      an important minimally invasive way to obtain detailed information regarding
      tumor biology. Reliable determination of circulating tumor-derived DNA, often
      present at a low quantity amidst an excess of normal DNA in plasma, would be of
      added value for screening and monitoring of cancer patients and for hypothesis
      generating studies in valuable retrospective cohorts. Our aim was to establish a
      workflow to simultaneously assess four hotspot estrogen receptor mutations
      (mESR1) in cfDNA isolated from only 200 MUL of plasma by means of uniplex or
      multiplex pre-amplification combined with digital PCR. This workflow was then
      applied in metastatic breast cancer (MBC) patients receiving systemic therapies
      for MBC. In accordance with previous studies, estrogen receptor mutations were
      more frequently detected in endocrine-treated MBC patients at progressive disease
      [34.1% (15/44)] than before the start of endocrine therapy [3.9% (2/51); P =
      0.001]. For a subset of samples, results were compared with analysis of these
      mutations by Oncomine-targeted next-generation sequencing, which, although
      requiring a higher cfDNA input, yielded concordant results. The data establish
      development and validation of a digital PCR workflow for the simultaneous
      detection of several tumor-derived mutations in minute amounts of cfDNA and show
      the potential of this workflow for use on archived volume-limited blood samples.

PMID- 30296590
TI  - Fra-2 is a novel candidate drug target expressed in the podocytes of lupus
      nephritis.
AB  - Lupus nephritis (LN) is a common and devastating complication caused by systemic
      lupus erythematosus. In this study, we evaluated the expression and mechanism of
      Fos-related antigen 2 (Fra-2) in LN. The results showed that Fra-2 was
      significantly increased in kidney biopsies of LN patients compared with healthy
      controls and other kidney disease in glomerular podocytes. The MRL/lpr mouse
      strain is a murine model of lupus, and it was used to study the mechanisms of Fra
      2 in LN. The results showed that Fra-2 was expressed in the glomerular podocytes.
      We investigated the effects of inflammatory stimuli on Fra-2 protein expression
      in the glomerular podocytes, and found that interferon gamma was most effective
      at increasing Fra-2 protein expression. Knockdown of Fra-2 using siRNA enhanced
      the protein expression of nephrin. Therefore, Fra-2 may be a specific drug target
      for podocyte injury in LN.

PMID- 30296591
TI  - Podocyte foot process width is a prediction marker for complete renal response at
      6 and 12 months after induction therapy in lupus nephritis.
AB  - Morphological change that includes diffuse effacement of podocyte foot processes
      is correlated with proteinuria in patients with lupus nephritis (LN). We
      collected the data of clinico-pathological parameters and assessed foot process
      width (FPW) as an index of podocyte effacement in 73 patients with LN who had
      undergone renal biopsy. The multivariate analysis revealed that female gender
      (OR: 5.288; 95%CI: 1.197-37.29; p = .0267) and FPW (OR = 0.999, 95%CI = 0.997
      0.999, p = .0150) were significantly predictive of a complete renal response (CR)
      at 6 months, while lymphocyte counts (OR = 1.002; 95%CI = 1.001-1.003, p = .0028)
      and FPW (OR = 0.998, 95%CI = 0.996-0.999, p = .0027) were significantly
      predictive of CR at 12 months. The cut-off point determined by the Classification
      and Regression Trees algorithm showed that FPW <908.3 nm provides the best
      performance for predicting patients who achieve CR at 12 months. A smaller FPW
      appears to be a predictive factor for CR at 6 and 12 months after induction
      therapy.

PMID- 30296592
TI  - The relationship between autophagy, increased neutrophil extracellular traps
      formation and endothelial dysfunction in chronic kidney disease.
AB  - In chronic kidney disease (CKD), the number of circulating neutrophils are
      increased, and this is usually accompanied by an increased basal activation
      state. However, the possible association between neutrophil extracellular traps
      (NETs) with vascular complications has not been evaluated. We assessed the
      relationship between NETs, autophagy and endothelial dysfunction in maintenance
      hemodialysis (MHD) patients. NET formation, neutrophil elastase (NE) activities,
      and serum nucleosome levels were measured in MHD (n = 60) and controls (n = 20).
      Basal NET formation were markedly increased in MHD patient compared to controls.
      After PMA stimulation, MHD neutrophils showed significantly increased NETs
      formation response than controls. The degree of NETs was strongly associated with
      lower flow-mediated dilatation(%) of brachial artery even after adjustment for
      cardiovascular risk factors and uremic toxins. Moreover, MHD neutrophils showed
      increased basal autophagy activity. Interestingly, the levels of NETs were
      markedly augmented after autophagy inhibition, suggesting a protective role of
      autophagy in excessive NET formation.

PMID- 30296593
TI  - A new case confirming and expanding the phenotype spectrum of ADAT3-related
      intellectual disability syndrome.
AB  - The present study describes two patients with clinical diagnosis of ID, from a
      consanguineous family in Israel. Whole exome sequencing identified a homozygous
      missense mutation in the ADAT3 gene. The clinical features of our patients were
      compared with several cases described in two recently published studies that
      documented clinical manifestation of this same mutation. Both affected siblings
      in our study expressed the previously described clinical features such as
      intellectual disability, strabismus, FTT/underweight, microcephaly and hypotonia.
      Interestingly, our patients suffered from additional clinical manifestations that
      were not detailed in the previous two studies, such as: gait difficulties,
      instability, teeth abnormalities, neuropathy and contractures of the hand wrist
      and fingers. We conclude that the ADAT3 gene mutation is responsible for ADAT3
      related ID syndrome, which induces the variety clinical manifestations exhibited
      by our patients. Further studies aimed at identifying and characterizing
      additional afflicted families worldwide will be required to obtain a more
      comprehensive understanding of this syndrome.

PMID- 30296594
TI  - AMPK promotes survival and adipogenesis of ischemia-challenged ADSCs in an
      autophagy-dependent manner.
AB  - Some studies have shown that transplanted fat tissues usually cannot survive for
      long if adipose-derived stem cells (ADSCs) are removed from the tissues in
      advance. It is more meaningful to explore the mechanism mediating survival and
      differentiation of ADSCs in the transplanted microenvironment. AMP-activated
      protein kinase (AMPK) has been shown to be one of the energy receptors that
      regulate many aspects of cellular metabolism. AMPK activation has been implicated
      in models of adult ischemic injury, but the mechanism and the regulating effects
      of AMPK on survival and adipogenesis of transplanted ADSCs are still little
      known. In this study, we simulated the transplanted microenvironment using oxygen
      glucose deprivation (OGD) to test the survival and adipogenesis of ADSCs. We
      found that OGD treatment triggered significant apoptosis and promoted autophagy.
      Simultaneously, OGD hindered the differentiation of ADSCs into mature adipocytes.
      After inhibiting AMPK, the OGD-induced apoptosis rate increased but autophagy was
      inhibited. The adipogenesis level also decreased. To show that the effects of
      AMPK on apoptosis and adipogenesis were autophagy-dependent, we pre-inhibited or
      pre-promoted autophagy with siATG7 or rapamycin while blocking AMPK. We found
      that inhibiting or improving autophagy exacerbated or alleviated the role of AMPK
      prohibition in apoptosis and adipogenesis. Furthermore, we showed that AMPK
      inhibition significantly lowered ULK1 activity but promoted mTOR activity, so
      that to inhibit autophagy. Our study shows that AMPK plays a protective role in
      maintaining survival and adipogenesis of OGD-challenged ADSCs partly by
      positively regulating autophagy. AMPK positively regulates autophagy by
      inhibiting mTOR but promoting ULK1 activity in OGD condition.

PMID- 30296595
TI  - Early Colonoscopy for Diverticular Bleeding Does Not Reduce Risk of Postdischarge
      Recurrent Bleeding: A Propensity Score-Matching Analysis.
AB  - BACKGROUND & AIMS: Colonoscopy within 24 hours (early colonoscopy) is recommended
      for patients with colonic diverticular bleeding, but it is unclear if this
      strategy improves postdischarge outcomes. We aimed to determine whether early
      colonoscopy is associated with decreased risk of rebleeding and hospital re
      admission within 30 days. METHODS: We performed a retrospective cohort study
      using Marketscan (Truven Health Analytics, Inc, Ann Arbor, MI), a nationwide
      insurance claims database. From January 2004 through September 2015, patients
      with a primary diagnosis of diverticular bleeding who underwent inpatient
      colonoscopy were included. We used propensity score matching to account for
      differences between recipients of early vs delayed colonoscopy. Multivariable
      logistic regression was performed to determine the association between early
      colonoscopy and rebleeding or hospital re-admission within 30 days of discharge.
      RESULTS: In total, 20,010 patients underwent colonoscopy for diverticular
      bleeding; 11,690 underwent early colonoscopy. After propensity matching, 8320
      pairs of patients were analyzed. In the matched analysis, higher proportions of
      patients who received early colonoscopy underwent additional colonoscopies (73%),
      compared with patients who did not receive early colonoscopy (4%) (P < .0001),
      but lower proportions received endoscopic interventions (3% vs 8%; P < .0001). On
      multivariable analysis, early colonoscopy (odds ratio [OR], 1.34; 95% CI, 1.08
      1.66; P = .007), transfusion requirement (OR, 2.31; 95% CI, 1.88-2.83; P <
      .0001), and baseline chronic kidney disease (OR, 2.13; 95% CI, 1.49-3.04; P <
      .0001) were associated with increased risk of rebleeding within 30 days. Early
      colonoscopy (OR, 1.18; 95% CI, 1.02-1.36; P = .03), endoscopic intervention (OR,
      1.37; 95% CI, 1.03-1.81; P = .03), transfusion requirement (OR, 2.17; 95% CI,
      1.88-2.51; P < .0001), coronary artery disease (OR, 1.27; 95% CI, 1.06-1.51; P =
      .009), and chronic kidney disease (OR, 1.98; 95% CI, 1.54-2.54; P < .0001) were
      associated with increased re-admission to the hospital within 30 days.
      CONCLUSIONS: In a propensity-matched analysis, we associated early colonoscopy
      with increased risk of rebleeding events and hospital re-admissions. However,
      these observations might be due to confounding factors.

PMID- 30296596
TI  - Stiffness memory of indirectly 3D-printed elastomer nanohybrid regulates
      chondrogenesis and osteogenesis of human mesenchymal stem cells.
AB  - The cellular microenvironment is dynamic, remodeling tissues lifelong. The
      biomechanical properties of the extracellular matrix (ECM) influence the function
      and differentiation of stem cells. While conventional artificial matrices or
      scaffolds for tissue engineering are primarily static models presenting well
      defined stiffness, they lack the responsive changes required in dynamic
      physiological settings. Engineering scaffolds with varying elastic moduli is
      possible, but often lead to stiffening and chemical crosslinking of the molecular
      structure with limited control over the scaffold architecture. A family of
      indirectly 3D printed elastomeric nanohybrid scaffolds with thermoresponsive
      mechanical properties that soften by reverse self-assembling at body temperature
      have been developed recently. The initial stiffness and subsequent stiffness
      relaxation of the scaffolds regulated proliferation and differentiation of human
      bone-marrow derived mesenchymal stem cells (hBM-MSCs) towards the chondrogenic
      and osteogenic lineages over 4 weeks, as measured by immunohistochemistry,
      histology, ELISA and qPCR. hBM-MSCs showed enhanced chondrogenic differentiation
      on softer scaffolds and osteogenic differentiation on stiffer ones, with similar
      relative expression to that of human femoral head tissue. Overall, stiffness
      relaxation favored osteogenic activity over chondrogenesis in vitro.

PMID- 30296598
TI  - Actin Polymerization Mediated by AtFH5 Directs the Polarity Establishment and
      Vesicle Trafficking for Pollen Germination in Arabidopsis.
AB  - The process of pollen germination is crucial for flowering plant reproduction,
      but the mechanisms through which pollen grains establish polarity and select
      germination sites are not well understood. In this study, we report that a formin
      family protein, AtFH5, is localized to the vesicles and rotates ahead of Lifeact
      mEGFP-labeled actin filaments during pollen germination. The translocation of
      AtFH5 to the plasma membrane initiates the assembly of a collar-like actin
      structure at the prospective germination site prior to germination. Genetic and
      pharmacological evidence further revealed an interdependent relationship between
      the mobility of AtFH5-labeled vesicles and the polymerization of actin filaments:
      vesicle-localized AtFH5 promotes actin assembly, and the polymerization and
      elongation of actin filaments, in turn, is essential for the mobility of AtFH5
      labeled vesicles in pollen grains. Taken together, our work revealed a molecular
      mechanism underlying the polarity establishment and vesicle mobility during
      pollen germination.

PMID- 30296597
TI  - Association between PPP2CA expression and colorectal cancer prognosis tumor
      marker prognostic study.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide.
      The aim of this study is to identify candidate genes by bioinformatics and
      investigate its clinical pathological characters and prognostic significance.
      METHOD: First, we identify differentially expressed genes (DEGs) in CRC by
      analyzing gene expression datasets from Gene Expression Omnibus (GEO). Then we
      performed a bioinformatics analysis by using Oncomine, STRING and Oncolnc
      databases. Gene Set Enrichment Analysis (GSEA) was performed using TCGA data set.
      Then, the protein expression level of PPP2CA was detected by immunohistochemistry
      in 196 pairs of primary colorectal cancer and corresponding non-tumor tissues.
      RESULT: Total 81 differential expressed genes were identified in the overlap of
      datasets. PPI network show the hub genes were CCND1, PPP2CA and YAP1. We
      investigated Oncomine databases and found that PPP2CA mRNA expression was lower
      in CRC tissues compared with normal tissues. Bioinformatics analysis indicated
      that PPP2CA expression was associated with epithelial-mesenchymal transition
      signaling pathway. Low expression of PPP2CA was associated with T stage, N stage,
      and M stage. Low expression of PPP2CA was associated with worse overall survival
      for CRC, and retained significance as an independent prognostic factor for CRC.
      CONCLUSION: PPP2CA may act as an oncogene in the progression of colorectal
      cancer. Moreover, PPP2CA has potential to be used as prognostic markers or
      therapeutic targets in CRC.

PMID- 30296599
TI  - A WW Domain-Containing Protein Forms Immune Nuclear Bodies against Begomoviruses.
AB  - The bipartite begomoviruses (Geminiviridae family), which are DNA viruses that
      replicate in the nucleus of infected cells, encode the nuclear shuttle protein
      (NSP) to facilitate the translocation of viral DNA from the nucleus to the
      cytoplasm via nuclear pores. This intracellular trafficking of NSP-DNA complexes
      is accessorized by the NSP-interacting guanosine triphosphatase (NIG) at the
      cytosolic side. Here, we report the nuclear redistribution of NIG by AtWWP1, a WW
      domain-containing protein that forms immune nuclear bodies (NBs) against
      begomoviruses. We demonstrated that AtWWP1 relocates NIG from the cytoplasm to
      the nucleus where it is confined to AtWWP1-NBs, suggesting that the NIG-AtWWP1
      interaction may interfere with the NIG pro-viral function associated with its
      cytosolic localization. Consistent with this assumption, loss of AtWWP1 function
      cuased plants more susceptible to begomovirus infection, whereas overexpression
      of AtWWP1 enhanced plant resistance to begomovirus. Furthermore, we found that a
      mutant version of AtWWP1 defective for NB formation was no longer capable of
      interacting with and relocating NIG to the nucleus and lost its immune function
      against begomovirus. The antiviral function of AtWWP1-NBs, however, could be
      antagonized by viral infection that induced either the disruption or a decrease
      in the number of AtWWP1-NBs. Collectively, these results led us to propose that
      AtWWP1 organizes nuclear structures into nuclear foci, which provide intrinsic
      immunity against begomovirus infection.

PMID- 30296600
TI  - Single-Particle Tracking for the Quantification of Membrane Protein Dynamics in
      Living Plant Cells.
AB  - The plasma membrane is a sophisticated, organized, and highly heterogeneous
      structure that compartmentalizes cellular processes. To decipher the biological
      processes involving membrane proteins, it is necessary to analyze their
      spatiotemporal dynamics. However, it is difficult to directly assess the dynamics
      and interactions of biomolecules in living cells using traditional biochemical
      methods. Single-particle tracking (SPT) methods for imaging and tracking single
      particles conjugated with fluorescent probes offer an ideal approach to acquire
      valuable and complementary information about dynamic intracellular processes. SPT
      can be used to quantitatively monitor the diverse motions of individual particles
      in living cells. SPT also provides super-spatiotemporal resolution that allows
      early-stage or rapid response information to be obtained for a better
      understanding of molecular basis of associated signal transduction processes.
      More importantly, SPT can be used to detect the motion paths of individual
      biomolecules in vivo and in situ, thus unveiling the dynamic behavior of the
      biomolecules that support developmental processes in living cells. In this
      review, we give an overview of SPT methods, from image acquisition to the
      detection of single particles, as well as tracking and data analysis. We also
      discuss recent applications of SPT methods in the field of plant biology to
      reveal the complex biological functions of membrane proteins.

PMID- 30296601
TI  - From Golden Rice to aSTARice: Bioengineering Astaxanthin Biosynthesis in Rice
      Endosperm.
AB  - Carotenoids are important phytonutrients with antioxidant properties, and are
      widely used in foods and feedstuffs as supplements. Astaxanthin, a red-colored
      ketocarotenoid, has strong antioxidant activity and thus can benefit human
      health. However, astaxanthin is not produced in most higher plants. Here we
      report the bioengineering of astaxanthin biosynthesis in rice endosperm by
      introducing four synthetic genes, sZmPSY1, sPaCrtI, sCrBKT, and sHpBHY, which
      encode the enzymes phytoene synthase, phytoene desaturase, beta-carotene
      ketolase, and beta-carotene hydroxylase, respectively. Transgneic overexpression
      of two (sZmPSY1 and sPaCrtI), three (sZmPSY1, sPaCrtI and sCrBKT), and all these
      four genes driven by rice endosperm-specific promoters established the
      carotenoid/ketocarotenoid/astaxanthin biosynthetic pathways in the endosperm and
      thus resulted in various types of germplasm, from the yellow-grained beta
      carotene-enriched Golden Rice to orange-red-grained Canthaxanthin Rice and
      Astaxanthin Rice, respectively. Grains of Astaxanthin Rice were enriched with
      astaxanthin in the endosperm and had higher antioxidant activity. These results
      proved that introduction of a minimal set of four transgenes enables de novo
      biosynthesis of astaxanthin in the rice endosperm. This work provides a
      successful example for synthetic biology in plants and biofortification in crops;
      the biofortified rice products generated by this study could be consumed as
      health-promoting foods and processed to produce dietary supplements.

PMID- 30296602
TI  - New human isolates of Trypanosoma cruzi confirm the predominance of hybrid
      lineages in domestic transmission cycle of the Argentinean Chaco.
AB  - Trypanosoma cruzi, the etiological agent of Chagas disease, was initially
      classified into 6 Discrete Typing Units (DTUs). The hybrid DTUs TcV and TcVI are
      the most frequent in domestic transmission cycles throughout the Southern Cone
      countries of South America. Here, we genotyped parasite isolates from human
      residents in Pampa del Indio municipality, Chaco, to further characterize the
      structure of T. cruzi populations, and to assess the degree of overlapping
      between the domestic and sylvatic transmission cycles. Artificial xenodiagnostic
      tests were performed to blood samples from 125 T. cruzi-seropositive people (age
      range, 3-70 years) who represented 14.3% of all seropositive residents
      identified. Parasites were obtained from feces of T. cruzi-infected Triatoma
      infestans examined 30 or 60 days after blood-feeding, and grown in vitro. The
      cultured parasites were genotyped by means of two PCR-based protocols. DTUs were
      determined from 39 (31%) patients residing in 28 dwellings. The only DTUs
      identified were TcV (92%) and TcVI (8-36%). Households with more than one
      parasite isolate consistently displayed the same DTU. Further sequencing of a
      fragment of the TcMK gene from selected samples argue against the occurrence of
      mixed TcV-TcVI infections in the study population. Sequencing data revealed an
      unexpected degree of genetic variability within TcV including two apparently
      robust subgroups of isolates. Our results for human residents confirm the
      predominance of hybrid lineages (TcV and to a much lesser extent TcVI) and the
      absence of sylvatic genotypes (TcI and TcIII) in (peri)domestic transmission
      cycles in the Argentinean Chaco area. 245 words.

PMID- 30296603
TI  - Proteogenomics: V international Caparica conference on analytical proteomics. V
      ICAP-2017.

PMID- 30296604
TI  - Design and operation of urban wastewater systems considering reliability, risk
      and resilience.
AB  - Reliability, risk and resilience are strongly related concepts and have been
      widely utilised in the context of water infrastructure performance analysis.
      However, there are many ways in which each measure can be formulated (depending
      on the reliability of what, risk to what from what, and resilience of what to
      what) and the relationships will differ depending on the formulations used. This
      research has developed a framework to explore the ways in which reliability, risk
      and resilience may be formulated, identifying possible components and knowledge
      required for calculation of each and formalising the conceptual relationships
      between specified and general resilience. This utilises the Safe & SuRe
      framework, which shows how threats to a water system can result in consequences
      for society, the economy and the environment, to enable the formulations to be
      derived in a logical manner and to ensure consistency in any comparisons. The
      framework is used to investigate the relationship between levels of reliability,
      risk and resilience provided by multiple operational control and design
      strategies for an urban wastewater system case study. The results highlight that,
      although reliability, risk and resilience values may exhibit correlations,
      designing for just one is insufficient: reliability, risk and resilience are
      complementary rather than interchangeable measures and one cannot be used as a
      substitute for another. Furthermore, it is shown that commonly used formulations
      address only a small fraction of the possibilities and a more comprehensive
      assessment of a system's response to threats is necessary to provide a
      comprehensive understanding of risk and resilience.

PMID- 30296605
TI  - Large greenhouse gases emissions from China's lakes and reservoirs.
AB  - Freshwaters are important sources of greenhouse gases (GHGs) to the atmosphere
      that may partially offset the terrestrial carbon sink. However, current emission
      estimates from inland waters remain uncertain due to data paucity in key regions
      with a large freshwater surface area, such as China. Here, we show that the areal
      fluxes of GHGs (carbon dioxide, methane, and nitrous oxide) from lakes and
      reservoirs in China are much larger than previous estimates. Our work summarized
      data from 310 lakes and 153 reservoirs, and revealed diffusive emissions of 1.56
      (95% confidence interval: 1.12-2.00) Tg C-CH4/y and 25.2 (20.8-29.5) Tg C-CO2/y
      from reservoirs and lakes. Chinese lakes and reservoirs emit 175.0 (134.7-215.3)
      Tg CO2 equivalent, with 73.4% of this forcing contributed by lakes. These aquatic
      sources are equivalent to 14.1%-22.6% of China's estimated terrestrial carbon
      sink. Our results suggest a disproportionally high contribution of China's
      reservoirs and lakes to national and global GHGs emissions, highlighting major
      data gaps and the need of including more artificial and natural lakes data from
      developing countries like China in global GHGs budgets.

PMID- 30296606
TI  - Selection of media for the design of ballasted flocculation processes.
AB  - Conventional clarification processes imply specific facility footprints that
      translate into important capital costs. Ballasted flocculation, consisting of
      injecting ballast medium to increase floc specific gravity and size, is being
      increasingly used in the water industry owing to its potential for design with
      very high superficial velocities. However, no systematic approach has yet been
      proposed to compare and select an appropriate ballast medium with respect to its
      specific gravity and size. In order to facilitate this procedure, this research
      project explores the hypothesis that flocculation performance is controlled by
      the surface area of the medium available for ballasted flocculation. This
      hypothesis was tested at laboratory scale by evaluating five ballast media with
      differing specific gravity and size: granular activated carbon, anthracite,
      silica sand, ilmenite, and magnetite sand having specific gravities of 1.24,
      1.45, 2.62, 3.70, and 5.08, respectively. Flocculation kinetics were monitored by
      measuring floc size through microscopy and with a camera installed directly on
      the jar-test beaker. Settling performance was monitored using turbidity
      measurements. This study shows that all ballast media, when expressed as total
      surface available during flocculation, required similar surface concentrations to
      achieve settled water turbidity near 1 NTU and lower. In addition, the effects
      from the ballast media size and specific gravity were lowered for settling time
      longer than 3 min. Inversely, for settling time of 12 s, larger and denser media
      produced lower settled water turbidity. For certain applications, lighter ballast
      media may be more economical because they offer more available surface area for a
      given mass concentration, hence reducing the amount of ballast media required in
      the flocculation tank. Finally, the ballast media point of zero charge and shape
      were not identified as key criteria for ballasted flocculation.

PMID- 30296607
TI  - Biological treatment of produced water coupled with recovery of neutral lipids.
AB  - Produced water (PW) is the largest waste stream generated by oil and gas
      industry. It is commonly treated by physical-chemical processes due to high salt
      content and poor biodegradability of water insoluble compounds, such as n
      alkanes. N-alkanes can represent a major fraction of organic contaminants within
      PW. In this study the possibility of simultaneous n - alkane biodegradation and
      production of neutral lipids in a concentrated PW stream with A. borkumenis SK2
      as the sole reactor inoculum was investigated. N-alkane removal efficiency up to
      99.6%, with influent alkane COD of 7.4 g/L, was achieved in a continuously
      operated reactor system. Gas chromatography results also showed that the majority
      of other non-polar compounds present in the PW were biodegraded. Biodegradation
      of n-alkanes was accompanied by simultaneous production of neutral lipids, mostly
      wax ester (WE)-alike compounds. We demonstrate, that under nutrient limited
      conditions and 108.9 +/- 3.3 mg/L residual n-alkane concentration the
      accumulation of extracellular WE-alike compounds can be up to 12 times higher
      compared to intracellular, reaching 3.08 grams per litre of reactor volume
      (g/Lreactor) extracellularly and 0.28 g/Lreactor intracellularly. With residual n
      alkane concentration of 311.5 +/- 34.2 mg/L accumulation of extracellular and
      intracellular WE-alike compounds can reach up to 6.15 and 0.91 g/Lreactor,
      respectively. To the best of our knowledge simultaneous PW treatment coupled with
      production of neutral lipids has never been demonstrated before.

PMID- 30296608
TI  - Applications of carbon quantum dots (CQDs) in membrane technologies: A review.
AB  - Carbon quantum dots (CQDs), which are a fascinating class of nanostructured
      carbons, have recently attracted extensive attention in the field of membrane
      technologies for their applications in separation processes. This is because they
      possess two unique advantages. Their productions are facile and inexpensive,
      while their physicochemical properties such as ultra-small sizes, good
      biocompatibility, high chemical inertness, tunable hydrophilicity, rich surface
      functional groups and antifouling characteristics are highly desirable.
      Leveraging on these, researchers have explored their utilizations in various
      membrane designs for reverse osmosis (RO), ultrafiltration (UF), nanofiltration
      (NF), forward osmosis (FO), pressure retarded osmosis (PRO), membrane
      distillation (MD), and organic solvent nanofiltration (OSN) processes. In
      particular, CQDs have especially stimulated exploration in the field of water
      treatment by membrane technologies since biocompatibility of membrane materials
      is of utmost importance to ensure safety of drinking water. In addition, CQDs are
      in a favorable position for achieving unprecedented performance of membrane
      separation processes in water treatment, in the light of substantial efficiency
      enhancement and antifouling propensity as discovered in recent studies. In this
      article, we will review the progress in the development of CQD incorporated
      membranes with discussions on their challenges and perspectives.

PMID- 30296609
TI  - Rhamnolipid from a Lysinibacillus sphaericus strain IITR51 and its potential
      application for dissolution of hydrophobic pesticides.
AB  - Rhamnolipid produced from a Lysinibacillus sphaericus IITR51 was characterized
      and its ability for dissolution of hydrophobic pesticides were evaluated. L.
      sphaericus produced 1.6 g/L of an anionic biosurfactant that reduced surface
      tension from 72 N/m to 52 N/m with 48% emulsification index. The biosurfactant
      was found stable over a wide range of pH (4.0-10.0), temperature (4-100  degrees
      C), salt concentration (2-14%) and was identified as rhamnolipid. At the
      concentration of 90 mg/L rhamnolipid showed enhanced dissolution of alpha-, beta
      endosulfan, and gamma-hexachlorocyclohexane up to 7.2, 2.9, and 1.8 folds,
      respectively. The bacterium utilized benzoic acid, chlorobenzene, 3- and 4
      chlorobenzoic acid as sole source of carbon and was found resistant to arsenic,
      lead and cadmium. Furthermore, the isolated biosurfactant showed antimicrobial
      activities against different pathogenic bacteria. The results obtained indicate
      the usefulness of rhamnolipid for enhanced dissolution and thereby increasing the
      bioavailability.

PMID- 30296611
TI  - Copper accumulation and toxicity in earthworms exposed to CuO nanomaterials:
      Effects of particle coating and soil ageing.
AB  - Engineered nanomaterials (ENMs) may be functionalised with a surface coating to
      enhance their properties, but the ecotoxicity of the coatings and how hazard
      changes with ageing in soil is poorly understood. This study determined the toxic
      effect of CuO ENMs with different chemical coatings on the earthworm (Eisenia
      fetida) in fresh soil, and then after one year in aged soil. In both experiments,
      earthworms were exposed for 14 days to the CuO materials at nominal
      concentrations of 200 and 1000 mg Cu kg-1 dry weight and compared to CuSO4. In
      the fresh soil experiment, CuO-COOH was found to be the most acutely toxic of the
      nanomaterials (survival, 20 +/- 50%), with tenfold increase of total Cu in the
      earthworms compared to controls. Sodium pump activity was reduced in most CuO ENM
      treatments, although not in the CuSO4 control. There was no evidence of
      glutathione depletion or the induction of superoxide dismutase (SOD) activity in
      any treatment. Histology showed a mild hypoplasia of mucous cells in the
      epidermis with some nanomaterials. In the aged soil, the CuO-NH4+ was the most
      acutely toxic ENM (survival 45 +/- 3%) and Cu accumulation was lower in the
      earthworms than in the fresh soil study. Depletion of tissue Mn and Zn
      concentrations were seen in earthworms in aged soil, while no significant effects
      on sodium pump or total glutathione were observed. Overall, the study showed some
      coating-dependent differences in ENM toxicity to earthworms which also changed
      after a year of ageing the soil.

PMID- 30296610
TI  - Climate change risk perception in global: Correlation with petroleum and liver
      disease: A meta-analysis.
AB  - BACKGROUND: Liver diseases have been bound to environmental factors, inclusive of
      air pollution. The exposure of workers to petrochemicals counts as a possible
      cause of Liver diseases, whereas results are inconsistent with the previous
      studies. In this study, a meta-analysis is conducted to assess the pooled risk.
      METHODS AND FINDING: A systematic search was performed by related researchers.
      Correlations are analyzed among petroleum and liver cirrhosis mortality, fatty
      liver, alanine amino transferase (abbreviated as ALT), aspartate amino
      transferase (abbreviated as AST). Pooled risk ratios (RR) with 95% confidence
      interval (CI) and effect size(ES) with 95% confidence interval are calculated.
      Sensitivity analysis and publication bias are also tested. Data are analyzed from
      5 studies involving 296 participants. Results are incorporated through adopting a
      random effects meta-analysis. Working in a petrochemical plant shall not increase
      the death risk posed by cirrhosis (RR = 0.44, 95% CI [0.36; 0.54]). Yet the
      incidence of fatty liver increases (RR = 1.22, 95% CI [1.21; 1.23]). Abnormal
      incidence of ALT and AST also increases. CONCLUSIONS: Occupational exposure plays
      an important role in causing ALT abnormalities and fatty liver among oil workers,
      but not a risk factor of cirrhosis, AST abnormalities and liver cancer.

PMID- 30296612
TI  - Deep Tissue Incision Enhances Spinal Dorsal Horn Neuron Activity During Static
      Isometric Muscle Contraction in Rats.
AB  - Translational correlates to pain with activities after deep tissue injury have
      been rarely studied. We hypothesized that deep tissue incision causes greater
      activation of nociception-transmitting neurons evoked by muscle contraction. In
      vivo neuronal activity was recorded in 203 dorsal horn neurons (DHNs) from 97
      rats after sham, skin-only, or skin + deep muscle incision. We evaluated DHN
      responses to static, isometric muscle contractions induced by direct electrical
      stimulation of the muscle. The effect of pancuronium on DHN response to
      contractions was also examined. Approximately 50% of DHNs with receptive fields
      in the hindpaw were excited during muscle contraction. One-second .5- and 1.0-g
      muscle contractions produced greater DHN activity after skin + deep muscle
      incision (median [interquartile range], 32 [5-39] impulses, P = .021; and 36 [26
      46] impulses, P = .006, respectively) than after sham (6 [0-21] and 15 [8-32]
      impulses, respectively). Neuromuscular blockade with pancuronium inhibited the
      muscle contractions and DHN activation during electrical stimulation,
      demonstrating contraction-induced activation. The greater response of spinal DHNs
      to static muscle contraction after skin + deep muscle incision may model and
      inform mechanisms of dynamic pain after surgery. PERSPECTIVE: Completion of
      various activities is an important milestone for recovery and hospital discharge
      after surgery. Skin + deep muscle incision caused greater activation of
      nociception-transmitting DHNs evoked by muscle contraction compared with skin
      only incision. This result suggests an important contribution of deep muscle
      injury to activity-evoked hyperalgesia after surgery.

PMID- 30296613
TI  - Generalization and Extinction of Concept-BasedPain-Related Fear.
AB  - In chronic pain, pain-related fear seems to overgeneralize to safe stimuli, thus
      contributing to excessive fear and avoidance behavior. Evidence shows that pain
      related fear can be acquired and generalized based on conceptual knowledge. Using
      a fear conditioning paradigm, we investigated whether this concept-based pain
      related fear could also be extinguished. During acquisition, exemplars of 1
      action category (conditioned stimuli [CSs]; eg, opening boxes) were followed by
      pain (CS+), whereas exemplars of another action category were not (CS-; eg,
      closing boxes). Participants reported more pain-related fear and expectancy
      toward exemplars of the CS+ category compared with those of the CS- category.
      During generalization, fear and expectancy spread to novel exemplars
      (generalization stimuli [GSs]) of the CS+ category (GS+), but not to those of the
      CS- category (GS-). During extinction, exemplars of both categories were
      presented in the absence of pain. At the end of extinction, participants no
      longer reported elevated fear or expectancy toward CS+ exemplars compared to CS-
      exemplars. These findings were not replicated in either the eye-blink startle or
      skin conductance measures. This is the first study to demonstrate extinction of
      concept-based pain-related fear, thus providing evidence for the potential of
      extinction-based techniques in the treatment of conceptual pain-related fear.
      PERSPECTIVE: This study demonstrates the acquisition, generalization, and
      extinction of concept-based pain-related fear in healthy participants. These are
      the first results to show that concept-based pain-related fear can be
      extinguished, suggesting that conceptual relationships between fear-inducing
      stimuli may also be important to consider in clinical practice.

PMID- 30296614
TI  - Does Sensorimotor Incongruence Trigger Pain and Sensory Disturbances in People
      With Chronic Low Back Pain? A Randomized Cross-Over Experiment.
AB  - Chronic low back pain (CLBP) has major public health implications, and underlying
      mechanisms are still unclear. Sensorimotor incongruence (SMI)-an ongoing mismatch
      between top-down motor output and predicted sensory feedback-may play a role in
      the course of chronic nonspecific low back pain. The hypothesis of this study was
      that the induction of SMI causes sensory disturbances and/or pain in people with
      CLBP and healthy volunteers. A sample of 66 people (33 people with CLBP and 33
      healthy volunteers) participated in a visual feedback experiment involving real
      time images of their own lower backs-either during movement or in a static
      position-provided via a live video feed. Experimental SMI was induced via
      distorting visual feedback of the lower back during movement. There were no
      significant differences in sensory disturbances or pain intensity between
      experimental SMI and the other movement conditions in people with CLBP and
      healthy volunteers (P > .05). Static visual feedback had a significant effect on
      the intensity of sensory disturbances in people with CLBP (P = .038) and healthy
      volunteers (P < .001). In conclusion, experimental SMI did not affect sensory
      disturbances or pain in either group. Therefore, the research hypothesis was not
      supported. PERSPECTIVE: The results of this study show that sensorimotor
      incongruence does not cause additional symptoms and pain in people with chronic
      low back pain. The conceptual premise that sensorimotor incongruence is an
      underlying contributor in the course of pain in this population is not supported.

PMID- 30296615
TI  - Functional specialization for feature-based and symmetry-based groupings in
      multiple object tracking.
AB  - Our vision systems utilize attention to process dynamic visual information
      everyday. Multiple object tracking (MOT) is widely used for studying sustained
      attention in dynamic environments. Previous research reported inter-target
      grouping based on feature similarity (e.g., targets sharing the same color, size,
      or shape) can facilitate tracking. A recent study also found that symmetric
      relation among targets in MOT tasks can automatically improve tracking
      performance, and a greater grouping effect based on symmetry and feature was
      observed. However, grouping based on multiple feature cues didn't produce a
      greater grouping effect than grouping based on one feature cue. Why were
      groupings based on symmetry and feature additive, but two feature-based groupings
      were not? How stimulus-driven inter-target groupings based on color or symmetry
      improve the goal-directed target tracking process remains unknown. We
      hypothesized that symmetry-based and feature-based groupings would involve
      different cortical and subcortical areas, and color-based and color-shape-based
      groupings would be manifested in significant activity in the same regions. This
      study used functional magnetic resonance imaging (fMRI) to identify cortical and
      subcortical areas involved in feature-based and symmetry-based groupings
      respectively during tracking. The results of our experiment showed that lateral
      occipital (LO) cortex is involved in symmetry-based grouping during tracking.
      Bilateral putamen, temporal parietal junction (TPJ), and frontal eye field (FEF)
      are involved in the feature-based grouping. Our findings likely indicate that
      stimulus-driven inter-target symmetry-based grouping and feature-based grouping
      improve goal-directed target tracking in different ways.

PMID- 30296616
TI  - Beneficial effects of n-3 polyunsaturated fatty acids administration in a partial
      lesion model of Parkinson's disease: The role of glia and NRf2 regulation.
AB  - Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been widely associated to
      beneficial effect over different neurodegenerative diseases. In the present
      study, we tested the potential therapeutic effect of docohexanoic acid (DHA) and
      its hydroxylated derivate, DHAH, in a partial lesion model of Parkinson's disease
      (PD). One month before and four months after the striatal lesion with 6-OHDA was
      made, the animals were daily treated with DHA (50 mg/kg), DHAH (50 mg/kg),
      vehicle or saline, by intragastric administration. Animal groups under n-3 PUFA
      treatments exhibited a trend to improve in amphetamine-induced rotations and
      cylinder test. The beneficial effect seen in behavioral studies were confirmed
      with TH immunostaining. TH+ fibers and TH+ neurons increased in the experimental
      groups treated with both n-3 PUFAs, DHA and DHAH. Moreover, the n-3 PUFAs
      administration decreased the astrogliosis and microgliosis, in both the striatum
      and substantia nigra (SN), with a higher decrease of GFAP+ and Iba-1+ cells for
      the DHAH treated group. This experimental group also revealed a positive effect
      on Nrf2 pathway regulation, decreasing the positive Nrf2 immmunostaining in the
      striatum and SN, which revealed a potential antioxidant effect of this compound.
      Taking together, these data suggest a positive effect of n-3 PUFAs
      administration, and more concretely of DHAH, for PD treatment as it exhibited
      positive results on dopaminergic system, neuroinflammation and oxidative stress.

PMID- 30296617
TI  - A potential gain-of-function variant of SLC9A6 leads to endosomal alkalinization
      and neuronal atrophy associated with Christianson Syndrome.
AB  - Loss-of-function mutations in the recycling endosomal (Na+,K+)/H+ exchanger gene
      SLC9A6/NHE6 result in overacidification and dysfunction of endosomal-lysosomal
      compartments, and cause a neurodevelopmental and degenerative form of X-linked
      intellectual disability called Christianson Syndrome (CS). However, knowledge of
      the disease heterogeneity of CS is limited. Here, we describe the clinical
      features and underlying molecular and cellular mechanisms associated with a CS
      patient carrying a de novo missense variant (p.Gly218Arg; G218R) of a conserved
      residue in its ion translocation domain that results in a potential gain-of
      function. The patient manifested several core symptoms typical of CS, including
      pronounced cognitive impairment, mutism, epilepsy, ataxia and microcephaly;
      however, deterioration of motor function often observed after the first decade of
      life in CS children with total loss of SLC9A6/NHE6 function was not evident. In
      transfected non-neuronal cells, complex glycosylation and half-life of the G218R
      were significantly decreased compared to the wild-type transporter. This
      correlated with elevated ubiquitination and partial proteasomal-mediated
      proteolysis of G218R. However, a major fraction was delivered to the plasma
      membrane and endocytic pathways. Compared to wild-type, G218R-containing
      endosomes were atypically alkaline and showed impaired uptake of recycling
      endosomal cargo. Moreover, instead of accumulating in recycling endosomes, G218R
      was redirected to multivesicular bodies/late endosomes and ejected
      extracellularly in exosomes rather than progressing to lysosomes for degradation.
      Attenuated acidification and trafficking of G218R-containing endosomes were also
      observed in transfected hippocampal neurons, and correlated with diminished
      dendritic branching and density of mature mushroom-shaped spines and increased
      appearance of filopodia-like protrusions. Collectively, these findings expand our
      understanding of the genetic diversity of CS and further elucidate a critical
      role for SLC9A6/NHE6 in fine-tuning recycling endosomal pH and cargo trafficking,
      processes crucial for the maintenance of neuronal polarity and mature synaptic
      structures.

PMID- 30296618
TI  - Vitronectin promotes the vascularization of porous polyethylene biomaterials.
AB  - Rapid implant vascularization is a prerequisite for successful biomaterial
      engraftment. Vitronectin (VN) is a matricellular glycoprotein well known for its
      capability to interact with growth factors, proteases, and protease
      inhibitors/receptors. Since such proteins are highly relevant for angiogenic
      processes, we hypothesized that VN contributes to the tissue integration of
      biomaterials. Employing different in vivo and ex vivo microscopy techniques,
      engraftment of porous polyethylene (PPE) implants was analyzed in the dorsal
      skinfold chamber model in wild-type (WT) and VN-/- mice. Upon PPE implantation,
      vascularization of this biomaterial was severely compromised in animals lacking
      this matricellular protein. Proteome profiling revealed that VN deficiency does
      not cause major changes in angiogenic protein composition in the implants
      suggesting that VN promotes PPE vascularization via mechanisms modulating the
      activity of angiogenic factors rather than by directly enriching them in the
      implant. Consequently, surface coating with recombinant VN (embedded in
      Matrigel(r)) accelerated implant vascularization in WT mice by enhancing the
      maturation of a vascular network. Thus, VN contributes to the engraftment of PPE
      implants by promoting the vascularization of this biomaterial. Surface coating
      with VN might provide a promising strategy to improve the vascularization of PPE
      implants without affecting the host's integrity. STATEMENT OF SIGNIFICANCE:
      Porous polyethylene (PPE) is a biomaterial frequently used in reconstructive
      surgery. The proper vascularization of PPE implants is a fundamental prerequisite
      for its successful engraftment in host tissue. Although the overall
      biocompatibility of PPE is good, there are less favorable application sites for
      its use in tissue reconstruction mostly characterized by low blood supply.
      Employing advanced in vivo microscopy methods and proteomic analyses in
      genetically engineered mice, we here describe a previously unrecognized function
      of vitronectin (VN) that enables this abundantly present glycoprotein to
      particularly promote the vascularization of PPE biomaterial. These properties of
      VN specifically facilitate the formation of a dense vessel network within the
      implant which relies on modulating the activity of angiogenic mediators rather
      than on the enrichment of these factors in the implant. Consequently, surface
      coating with this matricellular protein effectively accelerated and intensified
      implant vascularization which might be beneficial for its implementation at
      unfavorable sites for implantation without affecting the host's integrity.

PMID- 30296620
TI  - Design and development of pH-responsive polyurethane membranes for intravaginal
      release of nanomedicines.
AB  - The objective of this study was to develop and characterize a novel intravaginal
      membrane platform for pH-triggered release of nanoparticles (NPs), which is
      essential for efficient intravaginal delivery of certain effective but acid
      labile therapeutic agents for sexually transmitted infections, such as small
      interfering RNA (siRNA). A pH-responsive polyurethane (PU) was electrospun into a
      porous nanofibrous membrane. The diameters of the fibers, as well as the
      thickness and pore sizes of the membrane under dry and wet conditions (pH 4.5 and
      7.0), were determined from scanning electron microscopy (SEM) micrographs. pH
      dependent zeta-potential (zeta) of the membrane was evaluated using a SurPASS
      electrokinetic analyzer. VisiblexTM color-dyed polystyrene NPs (PSNs, 200 nm,
      COOH) and CCR5 siRNA-encapsulated solid lipid NPs (SLNs) were used for in vitro
      NP release studies in a vaginal fluid simulant (VFS) at pH 4.5 (normal
      physiological vaginal pH) and 7.0 (vaginal pH neutralization by semen). During 24
      h of incubation in VFS, close-to-zero PSNs (2 +/- 1%) and 28 +/- 4% SLNs were
      released through the PU membrane at pH 4.5, whereas the release of PSNs and SLNs
      significantly increased to 60 +/- 6% and 59 +/- 8% at pH 7.0, respectively. The
      pH-responsive release of NPs hinged on the electrostatic interaction between the
      pH-responsive membrane and the anionic NPs, and the change in pH-responsive
      morphology of the membrane. In vitro biocompatibility studies of the membrane
      showed no significant cytotoxicity to VK2/E6E7 human epithelial cells and Sup-T1
      human T-cells and no significant changes in the expression of pro-inflammatory
      cytokines (IL-6, IL-8, and IL-1beta). Overall, the porous pH-responsive PU
      membrane demonstrated its potential in serving as a "window" membrane in
      reservoir-type intravaginal rings (IVRs) for pH-responsive intravaginal release
      of NPs. STATEMENT OF SIGNIFICANCE: Stimuli-responsive intravaginal nanoparticle
      release is achieved for the first time through a new electrospun pH-responsive
      polyurethane (PU) semi-permeable membrane, which can serve as a "window" membrane
      in the reservoir-type IVR for the prevention of human immunodeficiency virus
      (HIV) transmission. Almost no release of nanoparticles was observed at normal pH
      in the female genital tract (in vaginal fluid simulant [VFS], at pH 4.5);
      however, a continuous release of NPs was observed at elevated pH in the female
      genital tract (in VFS, at pH 7.0). This pH-responsive intravaginal release can
      reduce side effect and drug resistance by avoiding unnecessary exposure. The PU
      semi-permeable membrane demonstrated potential use as biomaterials for "smart"
      intravaginal nanoparticle release and has great potential to protect women from
      HIV.

PMID- 30296619
TI  - Characterization of a Cell-Assembled extracellular Matrix and the effect of the
      devitalization process.
AB  - We have previously shown that the Cell-Assembled extracellular Matrix (CAM)
      synthesized by normal, human, skin fibroblasts in vitro can be assembled in a
      completely biological vascular graft that was successfully tested in the clinic.
      The goal of this study was to perform a detailed analysis of the composition and
      the organization of this truly bio-material. In addition, we investigated whether
      the devitalization process (dehydration) used to store the CAM, and thus, make
      the material available "off-the-shelf," could negatively affect its organization
      and mechanical properties. We demonstrated that neither the thickness nor the
      mechanical strength of CAM sheets were significantly changed by the
      dehydration/freezing/rehydration cycle. The identification of over 50
      extracellular matrix proteins highlighted the complex composition of the CAM.
      Histology showed intense collagen and glycosaminoglycan staining throughout the
      CAM sheet. The distribution of collagen I, collagen VI, thrombospondin-1,
      fibronectin-1, fibrillin-1, biglycan, decorin, lumican and versican showed
      various patterns that were not affected by the devitalization process.
      Transmission electron microscopy analysis revealed that the remarkably dense
      collagen network was oriented in the plane of the sheet and that neither fibril
      density nor diameter was changed by devitalization. Second harmonic generation
      microscopy revealed an intricate, multi-scale, native-like collagen fiber
      orientation. In conclusion, this bio-material displayed many tissue-like
      properties that could support normal cell-ECM interactions and allow implantation
      without triggering degradative responses from the host's innate immune system.
      This is consistent with its success in vivo. In addition, the CAM can be
      devitalized without affecting its mechanical or unique biological architecture.
      STATEMENT OF SIGNIFICANCE: The extracellular matrix (ECM) defines biological
      function and mechanical properties of tissues and organs. A number of promising
      tissue engineering approaches have used processed ECM from cadaver/animal tissues
      or cell-assembled ECM in vitro combined with scaffolds. We have shown the
      clinical potential of a scaffold-free approach based on an entirely biological
      material produced by human cells in culture without chemical processing. Here, we
      perform a comprehensive analysis of the properties of what can truly be called a
      bio-material. We also demonstrate that this material can be stored dried without
      losing its remarkable biological architecture.

PMID- 30296621
TI  - Micro-Raman high-pressure investigation on the malaria pigment hematin anhydride
      (beta-hematin).
AB  - The effect of pressure on the Raman and fluorescence spectra of hematin anhydride
      (beta-hematin) is reported. In a diamond-anvil cell, DAC, with applied pressures
      up to 41 kbar, the Raman spectrum undergoes a series of intensity enhancements
      and increases in energy for many of the Raman-active bands up to a pressure of
      ~27 kbar. At higher pressures, there is either a leveling out or a decrease in
      the energies of these vibrational modes. The fluorescence bands also undergo a
      series of pressure- sensitive changes where, up to 10 kbar, there is a marked
      quenching of the intensity of the emissive bands, which is accompanied by a net
      increase in energy of the vibrational bands. The results are interpreted in terms
      of a high-pressure phase change, to account for the Raman shifts, and a separate
      defect or surface site of the emissive state, which is more efficiently quenched
      at higher pressure.

PMID- 30296622
TI  - Patterns of Stroke Transfers and Identification of Predictors for Thrombectomy.
AB  - BACKGROUND: Interhospital transfers for endovascular thrombectomy (EVT)
      evaluation have increased since the publication of landmark neuroendovascular
      stroke trials in 2015. The lack of guidelines to select potential EVT candidates
      prior to transfer can lead to instances where, despite considerable costs and
      transport risks, transferred patients do not ultimately undergo EVT. Our aim was
      to characterize the patterns and identify predictors for EVT on transfer.
      METHODS: In this observational cohort study, we retrospectively analyzed patients
      with acute ischemic stroke (AIS) transferred to our institution for EVT
      evaluation from January 2015 to March 2016. Clinical and radiographic predictors
      for EVT on transfer were determined with multivariable logistic regression
      analysis. RESULTS: A total of 103 transfer patients with AIS were included in the
      study, and 52% were women. A higher collateral score (P < 0.01), a higher
      National Institutes of Health Stroke Scale (NIHSS) score (P < 0.01), computed
      tomography angiography (CTA) at referring hospital (P < 0.01), and large vessel
      occlusion on arrival CTA (P < 0.01) were significant in patients who underwent
      EVT on univariable analysis. More than half (61.1%) of transfers were futile and
      primarily related to absence of large vessel occlusion on arrival. A higher
      collateral score (P = 0.02), a higher NIHSS score (P = 0.006), and having
      undergone a CTA at the referring center (P = 0.002) remained the independent
      predictors of EVT. The C statistic for the model was 0.94. CONCLUSIONS: A higher
      collateral score, the acquisition of CTA imaging at the referring centers, and a
      higher NIHSS score independently predicted EVT on transfer.

PMID- 30296623
TI  - Navigated Transcranial Magnetic Stimulation In A Patient With A Cranioplasty In
      Situ: A Safe And Accurate Procedure.
AB  - BACKGROUND: and importance: Navigated Transcranial Magnetic Stimulation (nTMS) is
      a non-surgical mapping technique used in mapping of motor and language eloquent
      areas within and / or surrounding brain tumours. Previous reports support this as
      a safe technique with minor side effects associated with minor headaches and
      discomfort around the stimulation area. Currently there are no published reports
      concerning the accuracy and safety of this procedure in patients with a titanium
      cranioplasty in situ. CLINICAL PRESENTATION: A 59 year-old lady was diagnosed
      with a recurrent glioma in the context of increasing seizure frequency, left
      sided numbness and weakness. She was diagnosed with a WHO grade 2
      oligodendroglioma 10 years prior to her presentation which was initially treated
      with radiotherapy, and then surgical resection of this lesion five years later.
      The procedure was complicated with a wound infection, treated with a craniectomy
      and wound washout, followed by a titanium cranioplasty. Before proceeding with
      surgery for recurrence, nTMS was performed for motor mapping. No complications
      were identified. She underwent a craniotomy for tumour resection with GLIOLAN(r)
      and the tumour was completely removed. Intra-operatively, the direct cortical
      stimulation correlated with the pre-operative nTMS. The pathological diagnosis on
      recurrence was an Anaplastic Oligodendroglioma grade III and the patient is
      currently undergoing adjuvant chemotherapy. CONCLUSION: This report confirms that
      nTMS is a safe and accurate procedure in patients who have a titanium
      cranioplasty in situ.

PMID- 30296624
TI  - Cost Effectiveness of Dolutegravir as a First-Line Treatment Option in the HIV-1
      Infected Treatment-Naive Patients in Russia.
AB  - OBJECTIVES: To evaluate the cost effectiveness of dolutegravir +
      abacavir/lamivudine (DTG + ABC/3TC) compared with raltegravir +
      abacavir/lamivudine (RAL + ABC/3TC) and ritonavir-boosted darunavir +
      abacavir/lamivudine (DRV/r + ABC/3TC) in HIV-1-infected treatment-naive patients
      in Russia. METHODS: A dynamic Markov model was developed with five response
      states and six CD4+-based health states. Efficacy estimated as probability of
      viral suppression (HIV RNA <50 copies/ml) at 48 weeks was obtained from a
      published network meta-analysis. Baseline cohort characteristics and health state
      utilities were informed using DTG phase 3 clinical trials. Health care resource
      use was obtained from literature and costed using published unit costs. Costs
      (presented in Russian rubles) included antiretroviral drug costs; HIV management
      costs such as routine care; costs of treating cardiovascular conditions,
      opportunistic infections, and drug-related adverse effects; and mortality costs.
      A patient lifetime analysis was conducted using the societal perspective.
      Outcomes were quality-adjusted life-years (QALYs), life-years, incremental cost
      per QALY ratio, and incremental cost per responder. RESULTS: The viral
      suppression rate among patients receiving DTG + ABC/3TC was 71.7% compared with
      65.2% for RAL + ABC/3TC and 59.6% for DRV/r + ABC/3TC. The mean duration of
      response per patient was 116.6 months for DTG + ABC/3TC, 108.6 months for RAL +
      ABC/3TC, and 98.9 months for DRV/r + ABC/3TC. Total discounted costs for
      treatment over patient lifetime were RUB 2.89, 5.32, and 4.38 million for DTG +
      ABC/3TC, RAL + ABC/3TC, and DRV/r + ABC/3TC, respectively. Lifetime discounted
      QALYs were 12.73 for patients on DTG + ABC/3TC and 12.72 each for patients on RAL
      + ABC/3TC and DRV/r + ABC/3TC. DTG + ABC/3TC thus dominated the other two
      alternatives. CONCLUSIONS: With lower costs, higher response rates, and
      comparable QALYs, DTG + ABC/3TC can be considered as a cost-effective
      alternative.

PMID- 30296625
TI  - Multi-dimensional proprio-proximus machine learning for assessment of myocardial
      infarction.
AB  - This work presents a novel analysis methodology that utilises high-resolution,
      multi-dimensional information to better classify regions of the left ventricle
      after myocardial infarction. Specifically, the focus is to determine degree of
      infarction in regions of the left ventricle based on information extracted from
      cardiac magnetic resonance imaging. Enhanced classification accuracy is achieved
      using three mechanisms: Firstly, a plurality of indices/features is used in the
      pattern classification process, rather than a single index/feature (hence the
      term "multi-dimensional). Secondly, the method incorporates not only the
      indices/features of the region in consideration, but also indices/features from
      the neighbouring regions (hence the term "proprio-proximus"). Thirdly, advanced
      machine learning techniques are used for both feature selection and pattern
      classification process to ameliorate the effect of class-imbalance existing in
      the data. Numerical results from multiple experiments on real data showed that
      using multiple features improved the ability to distinguish between infarcted and
      non-infarcted remote segments, and using neighbouring information improved
      classification performance. The proposed methodology is general and can be
      adapted for the analysis of biological functions of other human organs.

PMID- 30296626
TI  - An iterative multi-atlas patch-based approach for cortex segmentation from
      neonatal MRI.
AB  - Brain structure analysis in the newborn is a major health issue. This is
      especially the case for preterm neonates, in order to obtain predictive
      information related to the child development. In particular, the cortex is a
      structure of interest, that can be observed in magnetic resonance imaging (MRI).
      However, neonatal MRI data present specific properties that make them challenging
      to process. In this context, multi-atlas approaches constitute an efficient
      strategy, taking advantage of images processed beforehand. The method proposed in
      this article relies on such a multi-atlas strategy. More precisely, it uses two
      paradigms: first, a non-local model based on patches; second, an iterative
      optimization scheme. Coupling both concepts allows us to consider patches related
      not only to the image information, but also to the current segmentation. This
      strategy is compared to other multi-atlas methods proposed in the literature.
      Experiments on dHCP datasets show that the proposed approach provides robust
      cortex segmentation results.

PMID- 30296627
TI  - Chemical profiling of the street cocktail drug 'nyaope' in South Africa using GC
      MS I: Stability studies of components of 'nyaope' in organic solvents.
AB  - Nyaope, a street drug commonly found in South Africa, is a mixture of low grade
      heroin, cannabis products, antiretroviral drugs and other materials added as
      cutting agents. It is a highly physiologically addictive substance which is
      smoked by users. Little work has been published on the chemical analysis and
      profiling of nyaope. Sample preparation prior to chromatographic or spectrometric
      analysis normally involves dissolution of the sample in an organic solvent. This
      study determined the most suitable organic solvent in which the common components
      of nyaope, namely Delta9-tetrahydrocannabinol, diamorphine, caffeine,
      dextromethorphan, phenacetin and the antiretrovirals efavirenz and nevirapine,
      which have different chemical characteristics, are stable during extraction and
      prior to analysis of nyaope samples i.e. autosampler stability. Street samples of
      cannabis (Delta9-tetrahydrocannabinol), heroin (diamorphine) and antiretrovirals
      were mixed to mimic a nyaope sample and dissolved in the organic solvents
      dichloromethane, ethanol, ethyl acetate, hexane, isopropanol and tertiary butyl
      alcohol. Analysis was performed after intervals of 0, 1, 6, 8, 24, 48 and 72h,
      prior to analysis by gas chromatography-mass spectrometry. Tertiary butyl alcohol
      resulted in the most stable extracts of the main nyaope components after 72h of
      storage. The analysis was also repeated on actual street samples of nyaope. These
      results show that tertiary butyl alcohol is a suitable solvent for sample
      preparation for the identification, comparison and profiling of nyaope samples.

PMID- 30296628
TI  - Bayesian interpretation of discrete class characteristics.
AB  - Bayesian interpretation of forensic evidence has become dominated by the
      likelihood ratio (LR) with a large LR generally considered favourable to the
      prosecution hypothesis, HP, over the defence hypothesis, HD. However, the LR
      simply quantifies by how much the prior odds ratio of the probability of HP
      relative to HD has been improved by the forensic evidence to provide a posterior
      ratio. Because the prior ratio is mostly neglected, the posterior ratio is
      largely unknown, regardless of the LR used to improve it. In fact, we show that
      the posterior ratio will only favour HP when LR is at least as large as the
      number of things that could possibly be the source of that evidence, all being
      equally able to contribute. This restriction severely limits the value of
      evidence to the prosecution when only a single, discrete class characteristic is
      used to match a subset of these things to the evidence. The limitation can be
      overcome by examining more than one individual characteristic, as long as they
      are independent of each other, as they are for the genotypes at multiple loci
      combined for DNA evidence. We present a criterion for determining how many such
      characteristics are required. Finally, we conclude that a frequentist
      interpretation is inappropriate as a measure of the strength of forensic evidence
      precisely because it only estimates the denominator of the LR.

PMID- 30296629
TI  - Facial approximation of Tycho Brahe's partial skull based on estimated data with
      TIVMI-AFA3D.
AB  - The virtual approach in physical and forensic anthropology is increasingly used
      to further analyze human remains, but also to propose new didactic means for
      visualization and dissemination of scientific results. Computerized facial
      approximation (FA) offers an alternative to manual methods, but usually requires
      a complete facial skeleton to allow for the estimation of the facial appearance
      of an individual. This paper presents the case of Tycho Brahe, Danish astronomer
      born during the XVIth century, whose remains were reanalyzed at the occasion of a
      short exhumation in 2010. Cranial remains of Brahe were poorly preserved, with
      only a partial facial skeleton, and virtual anthropology tools were used to
      estimate the missing parts of his skull. This 3D restoration was followed by a FA
      using TIVMI-AFA3D, subsequently textured with graphic tools. The result provided
      an interesting estimate that was compared with portraits of the astronomer. The
      impact of the missing data estimation was investigated by performing FAs on 10
      complete test subjects and the same 10 subjects after cropping and estimating 50%
      of the landmarks (reproducing the preservation state of Tycho Brahe's cranial
      remains). The comparison between the FA based on the complete and incomplete
      skulls of the same subject produced a visual assessment of the estimation impact
      on FAs which is relatively low. This procedure is an alternative to manual
      methods and offers a reproducible estimate of a face based on incomplete cranial
      remains. Although the case report concerns a historical individual, the robust
      automatic estimation of missing landmarks followed by a FA has value for forensic
      caseworks as a support to the identification process.

PMID- 30296630
TI  - Secondary extinction reduces reinstatement of threat expectancy and conditioned
      skin conductance responses in human fear conditioning.
AB  - BACKGROUND AND OBJECTIVES: Secondary extinction refers to the phenomenon that
      extinction of one conditioned stimulus (CS) results in the reduction of
      conditioned responses for other CSs conditioned with the same unconditioned
      stimulus (US). Previous research with rats has demonstrated that secondary
      extinction can interfere with the return of conditioned fear after a
      reinstatement manipulation. Here we investigated this phenomenon in two pre
      registered studies in humans. METHOD: In both experiments, distinct CSs were
      paired with an electrical stimulation. Next, conditioned reactions to both CSs
      were extinguished and thereafter reinstated through the administration of three
      unsignaled electrical stimulations. Crucially, before participants continued with
      the reinstatement test, half of the participants received secondary extinction
      trials whereas the other half did not receive these trials. RESULTS: Our results
      indicate that secondary extinction reduced reinstatement of threat expectancies
      and skin conductance responses, but the effect on skin conductance was only found
      in the second experiment. LIMITATIONS: The studies were conducted in a laboratory
      setting with healthy students. Additional research will be required to determine
      the feasibility of applying secondary extinction in a (sub)clinical context.
      CONCLUSIONS: To our knowledge, this is the first demonstration of secondary
      extinction and its effect on reinstatement of conditioned fear in humans. We
      relate our findings to the earlier research with rats and discuss their relevance
      for exposure therapy.

PMID- 30296631
TI  - Use of flow cytometry in forensic medicine: Current scenario and future
      prospects.
AB  - Several methodologies are being used on different biological, physical and
      chemical indicators to determine the postmortem interval (PMI); however, most of
      them are not completely accurate. Flow cytometry is an emerging technology widely
      used for single cell analysis in the field of clinical pathology. Studies on flow
      cytometry and its application in the field of forensic medicine were retrieved
      from systematic web searched of different databases including "MEDLINE",
      "ScienceDirect", "PubMed" and "Google Scholar" using keywords forensic science;
      forensic medicine; forensic investigation; flow cytometry; DNA; postmortem
      interval; vitreous humour with the last search performed in January 2018. A total
      of 43 publications have been reviewed, and out of them 22 studies met our
      criteria and have been cited in this article. A handful of studies have evaluated
      the application of flow cytometry in forensic medicine for estimation of the PMI
      and identification of the perpetrator of sexual assault cases. Flow cytometry is
      also useful for quantifying the ABH antigens in red blood cells as well as in
      other human samples that can be further used for personal identification. In
      conclusion, flow cytometry is more sensitive, faster and easy compared to the
      other methods of investigation, thus making it a preferred method. However, a
      large numbers of studies with the application of flow cytometry on different
      cases of death are required to establish a universally accepted rate of DNA
      degradation to avoid errors in judgment.

PMID- 30296632
TI  - High vigabatrin dosage is associated with lower risk of infantile spasms relapse
      among children with tuberous sclerosis complex.
AB  - After initially successful treatment of infantile spasms, the long-term
      cumulative risk of relapse approaches 50%, and there is no established protocol
      to mitigate this risk. Although vigabatrin may be an effective means to prevent
      relapse, there is little guidance as to ideal duration and dosage. Using a cohort
      of children with infantile spasms and tuberous sclerosis complex (TSC), we
      evaluated the potential association of post-response VGB treatment and the rate
      of infantile spasms relapse. Patients with infantile spasms and clinical response
      to vigabatrin were identified among a multicenter prospective observational
      cohort of children with TSC. For each patient we recorded dates of infantile
      spasms onset, response to vigabatrin, relapse (if any), and quantified duration
      and dosage of vigabatrin after response. Time to relapse as a function of
      vigabatrin exposure was evaluated using survival analyses. We identified 50
      children who responded to VGB. During a median follow-up of 16.6 months (IQR 10.3
      22.9), 12 (24%) patients subsequently relapsed after a median of 7.8 months (IQR
      3.1-9.6). Relapse occurred after VGB discontinuation in four patients, and during
      continued VGB treatment in the remaining eight cases. In survival analyses, risk
      of relapse was unaffected by the presence or absence of VGB treatment (HR 0.31,
      95%CI 0.01-28.4, P =  0.61), but weighted-average dosage was associated with
      marked reduction in relapse risk: Each 50 mg/kg/d increment in dosage was
      associated with 61% reduction in risk (HR 0.39, 95%CI 0.17 - 0.90, P =  0.026).
      This study suggests that the risk of infantile spasms relapse in TSC may be
      reduced by high-dose vigabatrin treatment.

PMID- 30296633
TI  - The use of involuntary treatment among older adults with cognitive impairment
      receiving nursing care at home: A cross-sectional study.
AB  - BACKGROUND: Respect for inherent dignity and individual autonomy is a basic
      principle in health care. However, several studies indicate that care-dependent
      older adults with a cognitive impairment, receiving nursing care at home, are at
      risk of care without their consent, referred to as 'involuntary treatment'. This
      includes the application of physical restraints (e.g. measures to prevent leaving
      bed or chair), psychotropic drugs (e.g. antidepressants, sedatives) and non
      consensual care (e.g. forced hygiene, hiding medication). Research about
      involuntary treatment is scarce and only recently first studies have been
      conducted. OBJECTIVE: To investigate 1) the prevalence of involuntary treatment,
      2) associated factors and 3) who requests and applies their use among older
      adults with cognitive impairment receiving nursing care at home. DESIGN: Cross-
      sectional study. SETTING: Homes of older adults receiving nursing care from
      district nurses in the eastern part of Belgium. PARTICIPANTS: Data were collected
      from 1194 randomly selected older adults with cognitive impairments receiving
      nursing care at home (mean age 83; 67% female). METHOD: District nurses completed
      an online questionnaire for each selected older adult in their caseload.
      Involuntary treatment was measured using a questionnaire identifying use of
      physical restraints, psychotropic medication and non-consensual care. In addition
      who requests involuntary treatment and who applies it was examined. Older adults
      sociodemographic characteristics, diagnosis of dementia, activities of daily
      living (ADL), cognitive status and informal caregiver burden were assessed.
      RESULTS: Involuntary treatment was used in 52% (95%; CI 49-55) of the total
      sample. Non-consensual care was most often used (73%; 95% CI 70-77), followed by
      psychotropic drugs (43%; 95% CI 39-47) and physical restraints (38%; 95% CI 35
      42). The use of involuntary treatment was associated with dependency for
      activities of daily life (OR 1.50; 95% CI 1.33-1.69), cognitive impairment (1.39;
      95% CI 1.25-1.55), informal caregiver burden (OR 1.05; 95% CI 1.01-1.10) and
      aging (OR 0.97; 95% CI 0.95-0.99). Informal caregivers (71%), followed by general
      practitioners (47%) most frequently requested the use of involuntary treatment,
      and nurses (81%) mostly applied it. CONCLUSION: In Belgium, involuntary treatment
      is often used in older adults with a cognitive impairment receiving nursing care
      at home. The implication of this study for clinical practice is that it confirms
      the need to develop an approach to prevent and reduce it. Further research is
      needed to plan and develop such an approach, in order to prevent and reduce the
      use of involuntary treatment.

PMID- 30296634
TI  - Intention, beliefs and mood assessed using electronic diaries predicts attendance
      at cardiac rehabilitation: An observational study.
AB  - BACKGROUND: Cardiac rehabilitationis effective in promoting
      physical/psychological recovery following acute coronary syndrome. Yet, rates of
      attendance at outpatient cardiac rehabilitation by eligible patients are low.
      OBJECTIVES: This study examined the determinants of attendance at outpatient
      cardiac rehabilitation in acute coronary syndrome patients following discharge
      until cardiac rehabilitation commencement. DESIGN: A weekly electronic diary
      measured cardiac-related cognitions and mood and examined their relation to
      attendance at outpatient cardiac rehabilitation. SETTINGS: Three United Kingdom
      National Health Service secondary care settings in two Health Board areas in
      Scotland. PARTICIPANTS: Acute coronary syndrome patients were recruited from
      March 2012 to June 2013 prior to hospital discharge. Of 488 eligible patients
      referred for cardiac rehabilitation, 214 consented. METHODS: Consecutive patients
      completed a pre-hospital discharge questionnaire targeting age, diagnosis, social
      class and smoking history. Acute coronary syndrome patients then completed a
      weekly electronic diary from the first week of discharge until the start of
      cardiac rehabilitation. Multilevel structural equation models estimated the
      effects of initial, i.e. baseline and rate of change in cardiac-related cognition
      and mood on attendance. Intention to attend cardiac rehabilitation was reflected,
      log transformed, reported thereafter as "do not intend". The role of "do not
      intend" was explored as a mediator of the relationship between cardiac-related
      cognition and mood on attendance. RESULTS: 166 participants provided, on average,
      5 weeks of diary entries before cardiac rehabilitation commenced. High intention
      (i.e. low "do not intend") to attend CR and its rate of increase over time
      predicted attendance. Low negative emotional representation, high perceived
      necessity, high confidence in maintaining function, low negative affect, and high
      positive affect following discharge predicted attendance at cardiac
      rehabilitation. The rate of change in cardiac-related mood and these cognitions
      was not predictive. Baseline and rate of change in "do not intend" entirely
      mediated relationships between a) perceived necessity, b) negative affect and
      attendance at cardiac rehabilitation. CONCLUSIONS: Negative affect in the first
      weeks following discharge represents the key challenge to a patient maintaining
      their intention to attend cardiac rehabilitation. Intervention to improve
      attendance should focus on improving intention to attend following discharge and
      during recovery by improving patient understanding of cardiac rehabilitation and
      reducing negative affect.

PMID- 30296635
TI  - The effectiveness of a coordinated preventive care approach for healthy ageing
      (UHCE) among older persons in five European cities: A pre-post controlled trial.
AB  - BACKGROUND: Older persons often have multiple health and social problems and need
      a variety of health services. A coordinated preventive approach that integrates
      the provision of health and social care services could promote healthy ageing.
      Such an approach can be organised differently, depending on the availability and
      organizational structures in the local context. Therefore, it is important to
      evaluate the effectiveness of a coordinated preventive care approach in various
      European settings. OBJECTIVES: This study explored the effects of a coordinated
      preventive health and social care approach on the lifestyle, health and quality
      of life of community-dwelling older persons in five European cities. DESIGN:
      International multi-center pre-post controlled trial. SETTING: Community settings
      in cities in the United Kingdom, Greece, Croatia, the Netherlands and Spain.
      PARTICIPANTS: 1844 community-dwelling older persons (mean age = 79.5; SD = 5.6).
      METHODS: The Urban Health Centres Europe (UHCE) approach consisted of a
      preventive multidimensional health assessment and, if a person was at-risk,
      coordinated care-pathways targeted at fall risk, appropriate medication use,
      loneliness and frailty. Intervention and control sites were chosen based on their
      location in distinct neighbourhoods in the participating cities. Persons in the
      catchment area of the intervention sites 'the intervention group' received the
      UHCE approach and persons in catchment areas of the control sites 'the control
      group' received care as usual. A questionnaire and two measurements were taken at
      baseline and at one-year follow-up to assess healthy lifestyle, fall risk,
      appropriate medication use, loneliness level, frailty, level of independence,
      health-related quality of life and care use. To evaluate differences in outcomes
      between intervention group and control group for the total study population, for
      those who received follow-up care-pathways and for each city separately
      (multilevel) logistic and linear regression analyses were used. RESULTS: Persons
      in the intervention group had less recurrent falls (OR = 0.65, 95% CI = 0.48;
      0.88) and lower frailty (B=-0.43, 95% CI= -0.65 to -0.22) at follow-up compared
      with persons in the control group. Physical health-related quality of life and
      mental well-being was better (B = 0.95; 95% CI = 0.14-1.76; and B = 1.50; 95% CI
      = 0.15-2.84 respectively). The effects of the UHCE approach were stronger in the
      subgroup of persons (53.6%) enrolled in care-pathways. CONCLUSIONS: Our study
      found promising but minor effects for the use of a coordinated preventive health
      and social care approach for the promotion of healthy ageing of older persons.
      Future studies should further evaluate effects of coordinated preventive health
      and social care aimed at healthy ageing. TRIAL REGISTRATION: ISRCTN registry
      number is ISRCTN52788952. Date of registration is 13/03/2017.

PMID- 30296636
TI  - Predictive model for growth of Bacillus cereus during cooling of cooked rice.
AB  - Bacillus cereus is frequently implicated in foodborne outbreaks associated with
      the consumption of cooked rice. The main contributing factors leading to
      outbreaks is rice cooked in large quantities and subsequently, inadequately
      chilled or stored at room temperatures for a prolonged period of time prior to
      consumption. Bacillus cereus growth in cooked rice inoculated with approximately
      2 log CFU/g of heat-shocked (80  degrees C/10 min) spores at several isothermal
      conditions (between 10 and 49  degrees C) was quantified. B. cereus populations
      were determined by plating on mannitol egg yolk polymyxin agar and incubating at
      30  degrees C for 24 h. Primary growth models, namely Baranyi, Huang, modified
      Gompertz, and logistic models were fitted to growth data. Specific growth rates
      from all four primary models were used to fit the modified Ratkowsky square-root
      model with respect to temperature. All four primary models were well fitted by
      the modified Ratkowsky model (R2 values from 0.90-0.99). Based on the goodness of
      fit secondary model statistics (R2, SSE, RMSE), the Baranyi model performed the
      best and was chosen for tertiary modeling. Acceptable prediction zone (APZ)
      analysis was performed for validation of the Baranyi model predictions during
      single rate exponential and biphasic linear cooling temperature profiles. For
      single rate cooling, 23 of the 24 predictions fell within the APZ (-1.0 to 0.5
      log CFU/g). For biphasic linear cooling, 26 of the 28 predictions fell within the
      APZ. The developed dynamic model can be used to predict potential B. cereus
      growth from spores in cooked rice during chilling and thus, support the
      disposition of product subject to cooling deviations.

PMID- 30296637
TI  - Thermoplastic starch/polybutylene adipate terephthalate film coated with gelatin
      containing nisin Z and lauric arginate for control of foodborne pathogens
      associated with chilled and frozen seafood.
AB  - In order to control foodborne pathogens on seafood products, an antimicrobial,
      thermoplastic starch/polybutylene adipate terephthalate (TPS/PBAT; 40/60) film
      was produced by coating gelatin (15% v/v) containing lauric arginate (LAE; 0.8
      mg/cm2), alone or combination with nisin Z (69.4 AU/cm2) to produce LAE-Gelatin
      TPS/PBAT and Nisin-LAE-Gelatin-TPS/PBAT films, respectively. Both films were
      investigated for control of Vibrio parahaemolyticus ATCC 17802 and Salmonella
      Typhimurium ATCC 14028 on bigeye snapper (Lutjanus lineolatus) and tiger prawn
      (Penaeus monodon) slices during long-term (28 days), refrigerated (4  degrees C;
      chilled) and frozen (-20  degrees C) storage up to 90 days. S. Typhimurium ATCC
      14028, experimentally inoculated onto bigeye snapper and tiger prawn slices,
      treated with the LAE-Gelatin-TPS/PBAT film, and stored at 4  degrees C was
      reduced 3.2 log10 CFU/g after 28 days and 7 log10 CFU/g after 21 days,
      respectively. Nisin-LAE-Gelatin-TPS/PBAT film reduced S. Typhimurium ATCC 14028
      on bigeye snapper and tiger prawn slices 3.5 log10 CFU/g after 28 days and 7
      log10 CFU/g after 14 days at 4  degrees C, respectively. The LAE-Gelatin-TPS/PBAT
      and Nisin-LAE-Gelatin-TPS/PBAT films and storage for 28 days at 4  degrees C
      reduced V. parahaemolyticus inoculated on chilled bigeye snapper slices
      approximately 2.6 and 4.2 log10 CFU/g, respectively. Both films reduced V.
      parahaemolyticus inoculated on chilled tiger prawn slices approximately 7.1 log10
      CFU/g after 28 days at 4  degrees C. The LAE-Gelatin-TPS/PBAT and Nisin-LAE
      Gelatin-TPS/PBAT films also reduced S. Typhimurium, inoculated on bigeye snapper
      and tiger prawn slices, 5.8 and 5.6 log10 CFU/g, respectively, after 60 days at 
      20  degrees C. V. parahaemolyticus was reduced by 5.8 log10 CFU/g on frozen
      bigeye snapper and tiger prawn slices after treatment with Nisin-LAE-Gelatin
      TPS/PBAT film after 14 and 21 days, respectively. However, the LAE-Gelatin
      TPS/PBAT film reduced V. parahaemolyticus 5.8 log10 CFU/g on both frozen seafood
      slices after 28 days. The results obtained from this study indicate the LAE
      Gelatin-TPS/PBAT and Nisin-LAE-Gelatin-TPS/PBAT films displayed excellent
      inhibition against S. Typhimurium and V. parahaemolyticus on chilled and frozen
      seafood.

PMID- 30296638
TI  - Treatment of cheese whey by a cross-flow anaerobic membrane bioreactor:
      Biological and filtration performance.
AB  - Whey, produced in large quantities during cheese production, is a rapidly
      fermentable high strength wastewater characterized by a high biodegradability and
      low alkalinity. In this study, a lab-scale cross-flow anaerobic membrane
      bioreactor was used to address the commonly experienced difficulties such as
      unstable reactor performance and unexpected biomass losses when treating whey
      wastewater with conventional anaerobic reactors. The anaerobic membrane
      bioreactor provided a stable treatment performance, i.e. more than 90% chemical
      oxygen demand removal, and moderate membrane fluxes between 8 and 11 L m-2 h-1
      could be obtained, applying a low cross-flow velocity of about 0.5 m s-1. Short
      term critical flux tests revealed that higher fluxes up to 36 L m-2 h-1 are
      possible at elevated cross-flow velocities and/or reduced mixed liquor suspended
      solids concentrations. Sludge filterability indicated by capillary suction time
      and specific resistance to filtration deteriorated throughout the study. Chemical
      cleaning efficiency gradually decreased, indicating irreversible membrane fouling
      during long term operation.

PMID- 30296639
TI  - Placental concentrations of essential, toxic, and understudied metals and
      relationships with birth outcomes in Chattanooga, TN.
AB  - BACKGROUND: Comprehensive examinations of placental metal concentrations and
      correlations with infant parameters are under-investigated. Chattanooga,
      Tennessee's consistently high incidence of low birth weight and potential for
      metal exposure provides an ideal opportunity to investigate potential
      correlations. OBJECTIVES: To investigate the associations between a wide variety
      of metals in placental tissue and multiple infant parameters. METHODS: A total of
      31 elements were screened via ICP-MS in 374 individual placental samples. Of
      those, 14 were quantifiable in > 86% of the samples. We examined correlations
      between metal concentrations and infant parameters (birth weight, gestational
      age, birth weight centile, placental weight, birth length and head
      circumference). We fit multivariable regression models to estimate the covariate
      adjusted associations of birth weight with ln-transformed concentrations of each
      of the 14 metals and used generalized additive models to examine nonlinear
      relationships. RESULTS: Some of the strongest relationships with infant
      parameters came from several lesser-studied metals. Placental rhodium
      concentrations were negatively correlated with almost all infant parameters. In
      the fully adjusted regression model, birth weight was significantly associated
      with several metals. On an IQR (25th to the 75th percentile) basis, estimated
      changes in birthweight were: for cobalt (82.5 g, IQR=6.05 ug/kg, p = 0.006), iron
      (-51.5 g, IQR = 171800 ug/kg, p = 0.030), manganese (-27.2 g, IQR=152.1 ug/kg, p
      = 0.017), lead (-72.7 g, IQR=16.55 ug/kg, p = 0.004) and rhodium (-1365.5 g, IQR
      = 0.33 ug/kg, p < 0.001). Finally, a generalized additive model showed
      significant nonlinear relationships between birth weight and concentrations of Co
      and Rh. CONCLUSIONS: Our comprehensive examination of placental metals illustrate
      many strong associations between lesser-studied metals and infant parameters.
      These data, in combination with our correlations of well-studied metals,
      illustrate a need to consider in utero exposure to a broad array of metals when
      considering fetal development.

PMID- 30296640
TI  - The tubercular badger and the uncertain curve:- The need for a multiple stressor
      approach in environmental radiation protection.
AB  - This article presents the results of a workshop held in Stirling, Scotland in
      June 2018, called to examine critically the effects of low-dose ionising
      radiation on the ecosphere. The meeting brought together participants from the
      fields of low- and high-dose radiobiology and those working in radioecology to
      discuss the effects that low doses of radiation have on non-human biota. In
      particular, the shape of the low-dose response relationship and the extent to
      which the effects of low-dose and chronic exposure may be predicted from high
      dose rate exposures were discussed. It was concluded that high dose effects were
      not predictive of low dose effects. It followed that the tools presently
      available were deemed insufficient to reliably predict risk of low dose exposures
      in ecosystems. The workshop participants agreed on three major recommendations
      for a path forward. First, as treating radiation as a single or unique stressor
      was considered insufficient, the development of a multidisciplinary approach is
      suggested to address key concerns about multiple stressors in the ecosphere.
      Second, agreed definitions are needed to deal with the multiplicity of factors
      determining outcome to low dose exposures as a term can have different meanings
      in different disciplines. Third, appropriate tools need to be developed to deal
      with the different time, space and organisation level scales. These
      recommendations permit a more accurate picture of prospective risks.

PMID- 30296641
TI  - A comparison of figure of merit (FOM) for various materials in adsorptive removal
      of benzene under ambient temperature and pressure.
AB  - To effectively remove gaseous pollutants from air using sorbents, a thorough
      knowledge of the actual sorption performance is needed at ambient conditions
      rather than at unrealistically high-pressure conditions, as is commonly presented
      in the literature. To this end, the sorbent capacities of gaseous benzene were
      evaluated at a constant sorbent bed inlet pressure (50 ppm or ~5 Pa) in 1 atm of
      N2, room temperature (298 K), a fixed flow rate (50 mL min-1), and equal outlet
      sampling intervals (5 min). The benzene adsorption patterns were investigated
      against six sorbent types in a total of 17 different forms: 1- zeolite in five
      forms: beads (ZB), ground to 212 um (ZG212), beads ground to 300 um (ZG300),
      coarsely ground/washed zeolite (ZWc), and coarsely ground/washed/thermally
      treated zeolite (ZTc), 2- activated carbon in two forms: 212 um (ACd212) and
      granular (ACdg), 3- Carbopack-X (CX), 4- Tenax TA (TA), 5- used black tea leaves
      of 150 or 300 um in three forms: dry (TD150/TD300), wet (TW150/TW300), and wet
      dust (TWd), and 6- used ground coffee in either dry (CD) or wet forms (CW).
      Accordingly, the largest adsorption capacities at 5 Pa (e.g., >10 mg g-1) were
      observed for ACd212 (79.1) and ACdg (73.6). Moderate values (e.g., 5 < < 10 mg g
      1) were obtained for ZG212 (7.98), CX (6.79), ZG300 (5.70), and ZB (5.58), while
      the remainder were far lower at < 5 mg g-1 (e.g., tea leaves, ground coffee, TA,
      ZWc, and ZTc). The experimental benzene capacities of the tested sorbents were
      further assessed by the Langmuir, Henry's law, Freundlich, Dubinin-Radushkevich,
      and Elovich isotherm models. The linearized Langmuir adsorption isotherms of
      ACd212, ACdg, and CX showed the presence of more than one adsorption site (i.e.,
      retrograde at the lowest pressures and two others at higher pressures). However,
      TA, zeolite, tea leaves, and ground coffee exhibited a type-V isotherm, wherein
      the sorption capacity continued to increase with loaded volume (i.e., multilayer
      adsorption). Thus, ACd212 has the best figure-of-merit based on a high 10%
      breakthrough volume (BTV) and low cost for real-world applications.

PMID- 30296642
TI  - Structure of a lytic polysaccharide monooxygenase from Aspergillus fumigatus and
      an engineered thermostable variant.
AB  - Lytic polysaccharide monooxygenases (LPMOs) are industrial enzymes which are
      gaining use in second generation bioethanol production from lignocellulose by
      acting in synergy with glycoside hydrolases. Here we present the X-ray crystal
      structure of an AA9 fungal LPMO from Aspergillus fumigatus and a variant which
      has been shown to have better performance at elevated temperatures. Based on the
      structures, thermal denaturation data and theoretical calculations, we provide a
      suggestion for the structural basis of the improved stability.

PMID- 30296643
TI  - Selectivity of original C-hexopyranosyl calix[4]arene conjugates towards lectins
      of different origin.
AB  - As a part of ongoing activities towards the design of ligands against pathogenic
      lectins, a synthesis of original alpha-C-galacto/alpha-C-manno/alpha-C
      fucopyranosyl glycomimetics based on a calix[4]arene scaffold and their binding
      evaluation is described. The interactions of the glycomimetics with seven lectins
      of various origins were carried out using agglutination inhibition assays. The
      1,3-alternate tetra-C-fucosylated ligand and its derivative having a tertBu group
      at the upper rim of the calix[4]arene scaffold were the most potent towards the
      AAL lectin family (RSL, AFL, AAL, AOL) and BC2L-C. As AFL and RSL originate from
      important human (Aspergillus fumigatus) and plant (Ralstonia solanacearum)
      pathogens, the inhibition potency of both leading structures was assessed by
      surface plasmon resonance. With AFL, both structures exhibited an approximately
      three orders of magnitude increase in affinity compared to the reference l
      fucose. The role of tertBu groups as "aglycon-assisted" events was illustrated by
      NMR. Furthermore, both compounds showed significantly increased ability to
      inhibit BC2L-C (from human pathogen Burkholderia cenocepacia) cell agglutination
      and were able to cross-link whole B. cenocepacia cells. Although the ligands
      failed to significantly inhibit the agglutination activity of LecA and LecB from
      Pseudomonas aeruginosa, tetra-C-galactosylated calix[4]arene with tertBu groups
      at the upper rim of the 1,3-alternate conformation inhibited P. aeruginosa
      biofilm formation efficiently. This systematic and comprehensive study highlights
      the fact that hydrolytically stable polyvalent C-glycomimetics should be regarded
      as potent and selective ligands capable of acting as antiadhesive agents.

PMID- 30296644
TI  - Co-morbidity with hypertrophic osteoarthropathy: A possible Iron Age Sarmatian
      case from the Volga steppe of Russia.
AB  - PURPOSE: Hypertrophic osteoarthropathy (HOA) is a condition that can be inherited
      or acquired. It causes diffuse periosteal new bone formation on the long bones,
      with a predilection for the appendicular skeleton. When acquired, it is a
      nonspecific indicator of systemic disease that arises following a primary
      condition. This paper reviews the palaeopathological literature associated with
      this rare condition. It also describes the first possible case of co-morbidity
      associated with hypertrophic osteoarthropathy in an adult skeleton (cal. BC 170 -
      1 cal. AD) from the mobile pastoralist Sarmatian culture of the Volga steppes of
      Russia. METHODS: Macroscopic and radiological examination provide differential
      diagnoses of the lesions, while clinical and bioarchaeological analyses offer
      insights into the possible experience of disease and social implications of care
      among the nomadic populations of Iron Age Russia. RESULTS: The analysis of Sk.
      6524.102 displays lesions that may be due to both hypertrophic osteoarthropathy
      and osteomalacia. The man was physically impaired and his participation in
      physically challenging activities would have been limited. CONCLUSIONS: The study
      stresses that co-morbidity is a key parameter when interpreting disease in past
      populations, particularly when the diagnosis involves hypertrophic
      osteoarthropathy. SIGNIFICANCE: This is the first case of hypertrophic
      osteoarthropathy identified in Eurasian prehistoric populations. The research
      emphasises the significance of co-morbidity in the past. LIMITATIONS: The
      diagnosis of co-morbid diseases in human remains is extremely complex and the
      conditions were identified as most probable by a process of elimination.
      SUGGESTIONS FOR FURTHER RESEARCH: Further studies should be dedicated to
      understanding co-morbidity in the past.

PMID- 30296645
TI  - A comparison among beta-caseins purified from milk of different species: Self
      assembling behaviour and immunogenicity potential.
AB  - Caseins are a family of proteins constituted by alpha-caseins (alphas-1 and
      alphas-2 caseins), beta-caseins and kappa-caseins. beta-caseins, in particular,
      show a temperature and concentration-dependent self-assembling behaviour.
      Recently, beta-casein micelles have been proposed as natural nanocarriers for the
      delivery of hydrophobic compounds, promoting their bioavailability. Until now,
      all studies regarding both chemical-physical characterization and applications of
      beta-caseins have employed the protein of bovine origin. However, it could be
      interesting to exploit the use of beta-caseins from other milk sources for their
      potential encapsulation ability and immunogenicity but, at present, no
      information on the self-assembling behaviour is available for beta-caseins from
      the milk of species different from bovine. In this work, for the first time, beta
      caseins from human milk and from donkey, goat, and sheep milk were purified and
      their self-assembling behaviour was compared to that of a commercial bovine beta
      casein, the only one for which the concentration and temperature aggregation
      behaviour is known. Furthermore, a preliminary evaluation of the immunogenicity
      potential of beta-casein from other milk sources has been performed by cross
      reaction experiments using anti-beta-casein antibodies from bovine origin. The
      results indicated a similar self-assembling profile among all beta-caseins
      examined compared to the bovine beta-casein, suggesting the possible use of beta
      casein from other milk sources as nanocarriers. Since donkey and human beta
      casein do not cross-react with bovine anti-beta-casein antibodies, they could be
      particularly interesting for the development of self-assembling systems with
      lower hypoallergenic potential.

PMID- 30296646
TI  - In situ phase transition of microemulsions for parenteral injection yielding
      lyotropic liquid crystalline carriers of the antitumor drug bufalin.
AB  - In this work, we used the small angle X-ray scattering (SAXS) method for
      controlled preparation of in situ forming sustained-release carriers for the
      antitumor drug bufalin (BUF), which has very poor solubility and a considerable
      cardiotoxicity in a non-encapsulated state. To that aim, we exploited the pseudo
      ternary phase diagram of an oil(O)/surfactant(S)/water(W) system containing
      medium chain capric/caprylic triglycerides (MCT) and a co-surfactant blend of
      Macrogol (15)-hydroxystearate (Solutol HS 15) and sorbitan monooleate (Span 80).
      Two compositions with different oil contents (sample B and C) were selected from
      the microemulsion region of the phase diagram in order to study the effect of the
      aqueous environment on their structural behavior. A phase transition from a
      microemulsion (ME) to a liquid crystalline phase (LC) was established by SAXS
      upon progressive dilution. The drug bufalin (BUF) was encapsulated in the
      microemulsions with low viscosity, whereas the release of the drug occurred from
      the in situ generated lamellar liquid crystalline structures. The formulations
      were characterized by SAXS, dynamic light scattering (DLS), cryogenic
      transmission electron microscopy (Cryo-TEM), rheology, drug loading and
      encapsulation efficiency, and in vitro release profiles. A correlation was
      suggested between the structures of the in situ phase-transition formed LCME
      formulations, the differences in their viscosities and drug release profiles. The
      performed cytotoxicity, cell apoptosis and pharmacokinetic experiments showed an
      enhanced bioavailability of BUF after encapsulation. These results suggest
      potential clinical applications for the obtained safe in situ phase-transition
      sustained-release formulations of BUF.

PMID- 30296647
TI  - Trace element concentrations in breast cancer patients.
AB  - Alterations in the circulating levels of trace elements have been observed in
      breast cancer (BC) patients. However, the relationships between these alterations
      and the metabolic and clinical consequences of BC are unknown. The treatment-of
      choice of BC is surgery followed by radiation therapy (RT). The present study was
      aimed at investigating: 1) the concentrations of several trace elements in BC
      patients, and their relationships with the intrinsic molecular subtypes of
      tumors; 2) the toxicological effect of RT. We studied 49 women with BC who were
      scheduled to receive RT following excision of the tumor. Plasma samples were
      obtained before and after the irradiation procedure. The control group was
      composed of 49 healthy women. Patients had significantly lower pre-RT
      concentrations of B, Cu, and Zn, and significantly higher concentrations of Sr
      than the control group. Irradiation was associated with a striking increase in
      plasma B concentrations, while Cu, Fe, Sr and Zn concentrations were not
      significantly different from pre-RT levels, albeit Sr and Zn showed non
      significant trends towards increases. The plasma concentrations of B, Cu, Fe, Sr,
      and Zn were associated with the tumor expression of hormone receptors, epidermal
      growth factor receptor 2, Ki67 antigen, as well as dermatitis and asthenia, all
      of which represent the main toxicological responses to RT.

PMID- 30296648
TI  - Treatment outcomes of breast cancer liver metastasis treated with stereotactic
      body radiotherapy.
AB  - BACKGROUND: To assess the outcomes of breast cancer liver metastasis (BCLM)
      treated with stereotactic body radiotherapy (SBRT) and systemic treatment.
      MATERIALS AND METHODS: Patients with oligometastasis at the time of liver
      metastasis (LM) or who became oligometastatic (<=5 metastases) after systemic
      treatment were assessed. Twenty-nine liver metastatic lesions were treated with a
      total of 54 Gy delivered in 3 fractions. The local control (LC), overall survival
      (OS), and progression-free survival (PFS) rates were calculated using Kaplan
      Meier analyses. RESULTS: A total of 22 patients with 29 liver metastatic lesions
      treated with liver SBRT between April 2013 and September 2017 were
      retrospectively analyzed. After a median follow-up time of 16.0 months (range 4.4
      59.4 months), 18 patients (82%) had disease recurrence, median of 7.4 months
      (range 1.0-27.9 months) after completion of liver SBRT. The 1- and 2-year OS
      rates were 85% and 57%, and the 1- and 2-year PFS rates were 38% and 8%,
      respectively. The 1- and 2-year LC rates were 100% and 88%, respectively. No
      significant prognostic factors, including disease extension, size of metastasis,
      number of liver metastasis and timing of liver metastasis, hormonal status
      affecting OS, PFS and LC were found. No patients experienced Grade 4 or 5
      toxicity; furthermore, only one patient experienced rib fracture 6 months after
      completion of treatment, and one patient had a duodenal ulcer. CONCLUSION: This
      study is the first to evaluate the feasibility of SBRT to BCLM patients. Liver
      SBRT is a conservative approach with excellent LC and limited toxicities.

PMID- 30296649
TI  - Harm-reduction and zero-tolerance maternal messages about college alcohol use.
AB  - Past cross-sectional research suggests that zero-tolerance messaging by parents
      of college students may be more effective than harm-reduction communication at
      reducing student alcohol risk. The current study employs longitudinal data to
      examine whether communication type interacts with student alcohol use to predict
      subsequent drinking outcomes. U.S. college students reported on their own
      exposure to zero-tolerance and harm-reduction maternal communication.
      Approximately seven months later, students completed measures of maternal alcohol
      approval and their own alcohol behaviors. The relationship between communication
      and subsequent alcohol behaviors depended on students' baseline drinking. For
      heavy drinkers, harm-reduction communication was associated with less alcohol use
      and consequences. For those who drank less than two drinks a week, zero-tolerance
      communication was associated with fewer negative consequences. Zero-tolerance
      communication was associated with perceiving mothers as less approving, while
      harm reduction communication was associated with perceiving mothers as more
      approving. There were indirect effects of communication on drinking through
      perceived maternal approval. While overall harm-reduction communication may lead
      students to perceive mothers as more approving of alcohol use, there may be
      contexts in which this type of communication is beneficial.

PMID- 30296650
TI  - Evaluation of SexedULTRA 4MTM sex-sorted semen in timed artificial insemination
      programs for mature beef cows.
AB  - An experiment was designed to compare fertility of SexedULTRA 4MTM sex-sorted
      semen and conventional, non-sex-sorted semen following either fixed-time
      artificial insemination (FTAI) or split-time artificial insemination (STAI) of
      mature suckled beef cows. Units of sex-sorted and conventional semen were
      produced using contemporaneous ejaculates from three commercially available
      sires. Units of conventional semen were generated with 25.0 * 106 live cells per
      0.25 ml straw prior to freezing, and units of sex-sorted semen were generated
      using the SexedULTRATM Genesis III sorting technology with 4.0 * 106 live cells
      per 0.25 ml straw prior to freezing. Sex-sorted units were sorted to contain X
      chromosome-bearing sperm cells at an accuracy level of >90%. Cows (n = 1620)
      across four herds were treated with the 7-d CO-Synch + CIDR protocol
      [administration of gonadotropin-releasing hormone (GnRH) and insertion of a
      progesterone insert (CIDR) on Day -10, followed by administration of
      prostaglandin F2alpha (PG) and removal of CIDR inserts on Day -3]. Cows were
      preassigned based on age, body condition score, and days postpartum to one of the
      following four treatments: FTAI with SexedULTRA 4MTM sex-sorted semen, FTAI with
      conventional semen, STAI with SexedULTRA 4MTM sex-sorted semen, or STAI with
      conventional semen. On Day -3, estrus detection aids (Estrotect(r)) were applied.
      For cows in FTAI treatments, AI was performed on Day 0 at 66 h after PG
      administration and CIDR removal, and 100 MUg GnRH was administered concurrent
      with AI. For cows in STAI treatments, AI was performed on either Day 0 or 1, at
      66 or 90 h after PG administration and CIDR removal, based on timing of estrus
      expression. On Day 1 at 90 h after PG administration and CIDR removal, 100 MUg
      GnRH was administered concurrent with AI to any STAI-treated cows that had failed
      to express estrus. Pregnancy rates to AI were affected (P = 0.04) by the
      interaction of bull and semen type. Greater pregnancy rates were obtained with
      conventional semen versus SexedULTRA 4MTM sex-sorted semen when using semen from
      Bull A (64% [176/277] versus 36% [100/278]; P < 0.0001) and Bull B (72% [200/277]
      versus 57% [156/276]; P < 0.01), whereas pregnancy rates to AI did not differ
      between conventional and SexedULTRA 4MTM sex-sorted semen when using semen from
      Bull C (58% [149/258] versus 52% [131/254]). Pregnancy rates did not differ
      significantly between cows inseminated using a STAI versus FTAI approach,
      regardless of whether insemination was performed with conventional semen (65%
      [265/409] versus 65% [260/403] or SexedULTRA 4MTM sex-sorted semen (50% [200/403]
      versus 48% [187/405]). However, due to the additional 24 h for potential estrus
      expression when performing STAI, total estrous response prior to AI was greater
      (P < 0.001) among cows receiving STAI (84%; 686/812) compared to FTAI (72%;
      585/808), and greater pregnancy rates (P < 0.0001) were obtained among cows that
      expressed estrus prior to AI. In summary, the relative fertility of SexedULTRA
      4MTM sex-sorted semen and conventional semen varied across bulls. Although
      overall pregnancy rates to timed AI did not differ between STAI and FTAI
      approaches, use of a STAI approach allowed for greater total estrous response
      prior to AI. Therefore, to achieve acceptable conception rates per unit and
      service the maximum number of cows with sex-sorted semen, one viable approach may
      be to use STAI to maximize total estrous response and restrict use of SexedULTRA
      4MTM sex-sorted to only those cows expressing estrus.

PMID- 30296651
TI  - Inhibin-A and Inhibin-B in stallions: Seasonal changes and changes after down
      regulation of the hypothalamic-pituitary-gonadal axis.
AB  - The biological function of inhibin is mediated by two heterodimers, inhibin-A and
      inhibin-B. The relative importance of inhibin-A and -B in male reproductive
      function varies considerably across species with inhibin-B predominating in many
      species, whereas inhibin-A appears relatively more important in rams. Research
      reported to date in stallions has examined total or immunoreactive (ir) inhibin
      which does not distinguish the two heterodimers. Therefore, the objective of this
      study was to characterize changes in inhibin-A and inhibin-B concentrations in
      stallions: 1) across season for a period of one year, and 2) after downregulation
      of the hypothalamic-pituitary-gonadal (HPG) axis. In Study one, serum samples
      were obtained monthly from five stallions for a period of one year. Serum
      concentrations of inhibin-A, inhibin-B, testosterone and estrone sulfate were
      determined by ELISA. In Study two, stallions were treated with the GnRH
      antagonist, acyline (n = 4; 330 mg/kg acyline IM) or vehicle control (n = 4;
      vehicle alone) every five days for 50 days. Plasma concentrations of inhibin-A
      and -B were determined by ELISA at Days 0, 6, 12, 22, 37, 59, 80, 87 and 104
      after initiation of acyline treatment. Testis volume was determined by
      ultrasonography at weekly intervals. In Study 1, both inhibin-A and inhibin-B
      showed seasonal changes in concentration with highest concentrations in
      increasing day length and lowest concentrations in short day lengths. Inhibin-B
      (overall mean 107.8 +/- 4.1 pg/mL) was present at 4.7-fold higher concentrations
      in serum than inhibin-A (overall mean 23.0 +/- 0.7 pg/mL). In Study 2, plasma
      concentrations of inhibin-B but not inhibin-A were significantly downregulated by
      administration of the GnRH antagonist, acyline. When the HPG axis was
      downregulated by acyline, testis volume was strongly correlated with inhibin-B (r
      = 0.73; P < 0.05) but not inhibin-A (r = 0.22; P = 0.20). In summary, inhibin-B
      appears to be the predominant form of inhibin in the stallion which undergoes
      seasonal regulation along with other reproductive parameters and is co-regulated
      with other endocrine parameters of the HPG axis.

PMID- 30296652
TI  - Equine chorionic gonadotropin induces in vitro follicular growth from the multi
      layered secondary developmental stage in cats.
AB  - Equine chorionic gonadotropin (eCG) has been commonly used to induce estrus in
      several felid species. However, the mechanisms by which this gonadotropin
      regulates cat folliculogenesis are still unclear. We investigated the
      responsiveness of cat ovarian follicles at different developmental stages to
      various eCG concentrations supplemented in vitro. Follicles were mechanically
      isolated from the ovaries of 22 cats and categorized into three developmental
      stages based on their morphology and diameter: 1) two-layered secondary follicle
      (SF), 100-150 MUm (n = 139); 2) multi-layered SF, 150-300 MUm (n = 154); and 3)
      early antral follicle (AF), >=300-500 MUm (n = 123). The follicles were then
      encapsulated in 0.5% (w/v) sodium alginate and cultured for 12 days in Minimum
      Essential Medium supplemented with 0, 0.05, 0.1 or 0.5 IU/mL eCG. Follicle and
      oocyte diameters were assessed every 3 days. On Day 12, mRNA expression levels of
      FHSR, LHCGR, GDF9, BMP15, CYP17A1, CYP19A1 and STAR were analyzed using real-time
      PCR. After being cultured for 12 days, follicle growth and mRNA expression of two
      layered SF were not influenced by eCG at all concentrations (P > 0.05). However,
      the concentration of eCG at 0.05 IU/mL stimulated follicular growth and gene
      expressions in the multi-layered SF and early AF (P < 0.05). Correspondingly, the
      diameter of oocytes in the multi-layered SF and early AF treated with 0.05 IU/mL
      eCG was unchanged. Considering the mRNA expression, the level of STAR was
      enhanced in the early AF (P < 0.05) and tended to increase in the multi-layered
      SF (P = 0.08) cultured in 0.05 IU/mL eCG, whereas the expression of other genes
      was not affected. In sum, the responsiveness of cat follicles to eCG is apparent
      from the multi-layered SF stage onward. The eCG supplementation at 0.05 IU/mL
      appeared to be optimal for the follicle culture in the domestic cats.

PMID- 30296653
TI  - Testosterone-retinoic acid signaling directs spermatogonial differentiation and
      seasonal spermatogenesis in the Plateau pika (Ochotona curzoniae).
AB  - During evolution, animals optimize their reproductive strategies to increase
      offspring survival. Seasonal breeders reproduce only during certain times of the
      year. In mammals, reproduction is tightly controlled by hypothalamus-pituitary
      gonad axis. Although pathways regulating gametogenesis in non-seasonal model
      species have been well established, molecular insights into seasonal reproduction
      are severely limited. Using the Plateau pika (Ochotona curzoniae), a small rodent
      animal species native to the Qinghai-Tibetan plateau, as a model, here we report
      that seasonal spermatogenesis is governed at the level of spermatogonial
      differentiation. In testis of the reproductively dormant animals,
      undifferentiated spermatogonia failed to differentiate and accumulated in the
      seminiferous tubules. RNA-seq analyses of the active and dormant testes revealed
      that genes modulating retinoic acid biogenesis and steriodogenesis were
      differentially regulated. A single injection of all-trans retinoic acid (ATRA)
      reinitiated spermatogenesis and inhibition the function of RA-degrading enzyme
      CYP26B1 for 10 days induced spermatogonial differentiation. Strikingly,
      testosterone injection reinitiated spermatogenesis in short day adapted animals.
      Testosterone provides a permissive environment of RA biogenesis and actions in
      testis, therefore, indirectly controls spermatogonial differentiation.
      Collectively, these findings provide a key mechanistic insight regarding the
      molecular regulation of seasonal reproduction in mammals.

PMID- 30296654
TI  - Evaluation of immunophenotyping, proliferation and osteogenic differentiation
      potential of SSEA-4 positive stem cells derived from pulp of deciduous teeth.
AB  - OBJECTIVES: Despite the increased interest in stem cells isolated from remnant
      pulp of deciduous teeth, no specific marker has been yet established for them.
      The present study aimed to investigate whether SSEA-4 (stage-specific embryonic
      antigen) would be a suitable marker to isolate stem cells from Human Exfoliated
      Deciduous teeth (SHEDs) in order to increase its differentiation potential toward
      osseous tissue. DESIGN: The SHEDs were isolated and the expression patterns of
      mesenchymal, hematopoietic and embryonic stem cell markers were assessed. The
      cells were then divided into two groups of SSEA-4(+) and unsorted SHEDs and the
      cell proliferation rate and population-doubling-time (PDT) were calculated.
      Subsequently, the differentiation potentials were examined through alizarin-red
      staining and Quantitative real time-PCR (qRT-PCR). RESULTS: Isolated cells were
      spindle-shaped with a high expression of mesenchymal stem cell markers and weak
      expression of hematopoietic markers. The mean expression of Oct-4 was 68.77%+/
      1.28. Despite similar proliferation rates between SSEA-4(+) and unsorted SHEDs,
      because of differences in the shape of the growth curves, PDT was lower in
      unsorted SHEDs (P = 0.2 * 10-4). Alizarin-red staining showed similar calcium
      deposition in both groups. Upon differentiation, the expression of osteocalcin
      was higher in unsorted SHEDs (P = 0.043), while, the expression of alkaline
      phosphatase was lower (P<0.001). The parathyroid hormone receptor (PTHR)
      expression was not significantly different (P = 0.0625). CONCLUSIONS: The results
      of the present study revealed that SHEDs have high differentiation potentials
      even in the unsorted cells. Although the SSEA-4-positive SHEDs showed slightly
      better osteogenic potential, the differences were not abundant to link SSEA-4
      expression with superior differentiation potency.

PMID- 30296655
TI  - Chemical composition of Pistacia vera L. oleoresin and its antibacterial, anti
      virulence and anti-biofilm activities against oral streptococci, including
      Streptococcus mutans.
AB  - OBJECTIVE: The aim of this study was to characterize the chemical composition of
      oleoresin of Pistacia vera L. and to determine its antimicrobial and anti
      virulence activity versus selected oral streptococci. DESIGN: A gaschromatografic
      analysis of the oleoresin was performed. The antimicrobial and anti-virulence
      activity of the oleoresin and its fractions was evaluated by the Minimum
      Inhibitory Concentration (MIC) and/or Minimum Bactericidal Concentration (MBC),
      biofilm production and haemolytic activity inhibition experiments. RESULTS: The
      oleoresin MBCs were >=1024 MUg/mL for all tested strains; the neutral and acidic
      fraction MBCs ranged from 128 to 2048 MUg/mL. Essential oil's MBCs (from 256 to
      2048 MUg/mL) were almost identical to MICs, suggesting a bactericidal effect. P.
      vera oleoresin at sub-lethal concentrations significantly reduced biofilm
      production by Streptococcus mutans (up to 49.4%) and by Streptococcus sanguinis
      (up to 71.2%). In addition, the acidic fraction showed a specific anti-biofilm
      activity against S. mutans (up to 41.3% reduction). A significant dose-dependent
      reduction in the haemolytic activity of S. mutans (up to 65.9%) and of S.
      anginosus (up to 78.3%) was observed after growth in the presence of oleoresin at
      sub-lethal concentrations. The acidic fraction reduced haemolytic activity (up to
      54.3% at 64 MUg/mL) of S. mutans only. CONCLUSIONS: Given the anti-virulence
      activity of the P. vera oleoresin and its acidic fraction against S. mutans, our
      findings suggest their potential use in oral hygiene. These data represent the
      first step in the exploitation of P. vera L. oleoresin.

PMID- 30296656
TI  - Investigation of flow dynamics of phosphate fertilizer production reactors using
      radiotracer technique.
AB  - Radiotracer investigations were carried out in two identical phosphoric acid
      production reactors and a triple super phosphate (TSP) production reactor in
      three different plants in Tunisia. The main objective of the study was to
      investigate and compare their flow behavior and identify flow abnormalities, if
      any. Residence time distribution (RTD) of the process material (ore pulp) was
      measured in the three reactors using Iodine-131. The measured RTDs were treated
      and analyzed to obtain flow parameters such as the mean residence time (MRT),
      dead volume, and extent of bypassing. The treated RTD curves were modeled using a
      suitable mathematical model, and the values of the parameters were obtained. The
      results of the investigations were used to evaluate and compare the flow
      performance of the reactors, quantify the degree of mixing, and visualize the
      prevailing flow patterns. The results of the investigations are expected to be
      used to make necessary modifications to enhance the efficiency and optimize the
      performance of the reactors or the production process.

PMID- 30296657
TI  - Time-Integrative Passive sampling combined with TOxicity Profiling (TIPTOP): an
      effect-based strategy for cost-effective chemical water quality assessment.
AB  - This study aimed at demonstrating that effect-based monitoring with passive
      sampling followed by toxicity profiling is more protective and cost-effective
      than the current chemical water quality assessment strategy consisting of
      compound-by-compound chemical analysis of selected substances in grab samples.
      Passive samplers were deployed in the Dutch river delta and in WWTP effluents.
      Their extracts were tested in a battery of bioassays and chemically analyzed to
      obtain toxicity and chemical profiles, respectively. Chemical concentrations in
      water were retrieved from publicly available databases. Seven different
      strategies were used to interpret the chemical and toxicity profiles in terms of
      ecological risk. They all indicated that the river sampling locations were
      relatively clean. Chemical-based monitoring resulted for many substances in
      measurements below detection limit and could only explain <20% of the observed in
      vitro toxicity. Effect-based monitoring yielded more informative conclusions as
      it allowed for ranking the sampling sites and for estimating a margin-of-exposure
      towards chronic effect ranges. Effect-based monitoring was also cheaper and more
      cost-effective (i.e. yielding more information per euro spent). Based on its
      identified strengths, weaknesses, opportunities, and threats (SWOT), a future
      strategy for effect-based monitoring has been proposed.

PMID- 30296659
TI  - Metaphors we learn by: Directed motor action improves word learning.
AB  - Can performing simple motor actions help people learn the meanings of words? Here
      we show that placing vocabulary flashcards in particular locations after studying
      them helps students learn the definitions of novel words with positive or
      negative emotional valence. After studying each card, participants placed it on
      one of two shelves (top or bottom), according to its valence. Participants who
      were instructed to place positive cards on the top shelf and negative cards on
      the bottom shelf, consistent with metaphors that link "good" with "up,"
      remembered the words' definitions better than participants who followed the
      opposite spatial mapping, and better than control participants who placed all of
      the cards on the desktop. Saying "up" and "down" after studying the cards was
      ineffective, suggesting a privileged role for motor action in activating space
      valence associations that partly constitute the meanings of emotionally charged
      words. These results provide a first demonstration that mental metaphors can be
      activated strategically to improve (or impair) word learning: We call this the
      strategic use of mental metaphor (SUMM) effect. Even when multiple factors known
      to enhance encoding of verbal materials into long-term memory were matched across
      conditions (e.g., study time, repetition, distinctiveness, depth of processing),
      metaphor-congruent motor actions led to better elaborated, more durable memories.

PMID- 30296658
TI  - The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties.
AB  - The oncogene ERG encodes an ETS family transcription factor and is implicated in
      blood, vascular, and bone development and in prostate, blood, and bone cancer.
      The ERG gene is alternatively spliced; of particular interest is its cassette
      exon 7b which adds 24 amino acids, in frame, to the transcriptional activation
      domain. Higher exon 7b inclusion rates are associated with increased cell
      proliferation and advanced prostate cancer. The 24 amino acids encoded by exon 7b
      show evolutionary conservation from humans to echinoderms, highlighting their
      functional importance. Throughout evolution, these 24 amino acids are encoded by
      a distinct short exon. Splice-switching oligonucleotides based on morpholino
      chemistry were designed to induce skipping of ERG exon 7b in MG63 osteosarcoma
      and VCaP prostate cancer cells. Induction of exon 7b skipping reduced cell
      proliferation and invasion, increased apoptosis in vitro, and reduced xenograft
      growth in vivo. We also show that ERG's exon 7b is required for the induction of
      tissue nonspecific alkaline phosphatase. Together, these findings show that the
      evolutionarily conserved cassette exon 7b is central to ERG's oncogenic
      properties.

PMID- 30296660
TI  - Development of the sea urchin Heliocidaris crassispina from Hong Kong is robust
      to ocean acidification and copper contamination.
AB  - Metallic pollution is of particular concern in coastal cities. In the Asian
      megacity of Hong Kong, despite water qualities have improved over the past
      decade, some local zones are still particularly affected and could represent
      sinks for remobilization of labile toxic species such as copper. Ocean
      acidification is expected to increase the fraction of the most toxic form of
      copper (Cu2+) by 2.3-folds by 2100 (pH ~7.7), increasing its bioavailability to
      marine organisms. Additionally, multiple stressors are likely to exert
      concomitant effects (additive, synergic or antagonist) on the organisms living in
      the sea. Here, we tested the hypothesis that copper-contaminated waters are more
      toxic to sea urchin larvae under future pH conditions. We exposed sea urchin
      embryos and larvae to two low-pH and two copper treatments (0.1 and 1.0 MUM) in
      three separate experiments. Over the short time typically used for toxicity tests
      (up to 4-arm plutei, i.e. 3 days), larvae of the sea urchin Heliocidaris
      crassispina were robust and survived the copper levels present in Hong Kong
      waters today (<=0.19 MUM) as well as the average pH projected for 2100. We,
      however, observed significant mortality with lowering pH in the longer, single
      stressor experiment (Expt A: 8-arm plutei, i.e. 9 days). Abnormality and arm
      asymmetry were significantly increased by pH or/and by copper presence (depending
      on the experiment and copper level). Body size (d3; but not body growth rates in
      Expt A) was significantly reduced by both lowered pH and added copper. Larval
      respiration (Expt A) was doubled by a decrease at pHT from 8.0 to 7.3 on d6. In
      Expt B1.0 and B0.1, larval morphology (relative arm lengths and stomach volume)
      were affected by at least one of the two investigated factors. Although the
      larvae appeared robust, these sub-lethal effects may have indirect consequences
      on feeding, swimming and ultimately survival. The complex relationship between pH
      and metal speciation/uptake is not well-characterized and further investigations
      are urgently needed to detangle the mechanisms involved and to identify possible
      caveats in routinely used toxicity tests.

PMID- 30296661
TI  - Does switching to a second-generation tyrosine kinase inhibitor or increasing
      imatinib dose have long-term benefits in chronic myeloid leukemia patients with
      suboptimal responses under upfront standard-dose of imatinib?

PMID- 30296662
TI  - Innate immunosensing of DNA in cellular senescence.
AB  - Senescence is a multistep cellular program featuring a stable cell cycle arrest,
      which occurs upon exposure to various stressors. Senescent cells exhibit
      metabolic activity and hypertrophy and produce a multitude of factors with both
      cell intrinsic as well as non-cell autonomous functions. These factors are
      collectively referred to as the senescence-associated secretory phenotype (SASP).
      Recently, the DNA sensor cyclic GMP AMP synthase (cGAS) and the adaptor
      stimulator of interferon genes (STING) have been reported to be critically
      involved in the regulation of senescence. This suggests that cGAS has an
      important function as a more general cell intrinsic stress sensor with
      implications for multiple senescence-associated diseases.

PMID- 30296663
TI  - Diet and physical activity in the association between depression and metabolic
      syndrome: Constances study.
AB  - BACKGROUND: The association between depression and the metabolic syndrome remains
      poorly understood. Diet and physical activity may partly explain this
      association. METHODS: Baseline data on 64,861 subjects from the French population
      based Constances cohort was analyzed. Depressive symptoms were determined with
      the Center of Epidemiologic Studies Depression (CES-D) scale. A CES-D score >= 19
      combined with self-reported limitations related to depressive symptoms was used
      to define depression. The metabolic syndrome was defined according to the
      International Diabetes Federation criteria. Dietary patterns were determined with
      a food frequency questionnaire and a principal component analysis. Physical
      activity was measured with 3 questions resulting in a composite 6-point scale.
      Associations between depression and the metabolic syndrome were estimated through
      logistic regression and path analysis. RESULTS: The odds-ratios (95% confidence
      interval) for the association between depression and the metabolic syndrome,
      adjusting for age, sex, education and income, was 1.75 (1.57-1.96). The path
      analysis showed that 23% of this association was explained by diet and physical
      activity, 67% being attributed to physical activity. LIMITATIONS: The cross
      sectional nature of the analyses warrants the results to be confirmed by
      longitudinal analyses. CONCLUSION: Diet and physical activity might partially
      explain the association between depressive symptoms and metabolic syndrome but
      other factors (e.g. inflammatory factors) are involved.

PMID- 30296664
TI  - Transient epileptic and global amnesia: Real-life differential diagnosis.
AB  - OBJECTIVE: Transient epileptic amnesia (TEA) is an underestimated condition in
      emergency clinical setting, where most of transient amnesic episodes tend to be
      classified as transient global amnesia (TGA). We designed this study to evaluate
      the actual frequency of TEA in a real-life scenario and to highlight the features
      that can help clinicians distinguishing it from TGA. METHODS: We retrospectively
      collected clinical data of 83 patients who accessed our emergency ward for an
      abrupt onset of amnesic disorder, initially interpreted as TGA. All patients
      underwent neurological evaluation, magnetic resonance imaging (MRI) scan, and
      standard 21-channel scalp electroencephalography (EEG) recording (standard EEG
      [st-EEG]). Moreover, patients with borderline epileptiform abnormalities on st
      EEG or with normal st-EEG but high clinical suspicion for TEA underwent a 16
      channel 24-hour ambulatory EEG (24-h EEG). Clinical features, neurophysiological,
      and neuroimaging data were analyzed and compared in the two groups (TEA and TGA).
      RESULTS: Diagnosis of TEA, according to Zeman's criteria, was made in 15 patients
      (18%). From a clinical point of view recurrence (p < .001) and atypical symptoms
      such as confusion or language disorder (TGA plus manifestations), appear to be
      key elements in order to discriminate between TEA and TGA (80% of patients with
      TEA vs 7.8% of patients with TGA; p < .001). In our sample, duration of the
      episodes did not significantly differ between TGA and TEA, even though it is
      usually described as shorter for TEA. This result could be related with a
      prolonged postictal state in these patients. The analysis of st-EEG results
      evidenced low sensitivity for interictal epileptiform abnormalities (IEAs)
      detection (52.3%), with not conclusive data in distinguishing TEA from TGA. On
      the contrary, 24-h EEG showed IEAs in all patients with epilepsy, mostly during
      sleep, suggesting an essential diagnostic role of long-lasting EEG recording for
      TEA. Finally, structural abnormalities were more frequent in patients with TEA
      (26.6%). In the group with TGA, the only imaging alteration found was diffusion
      weighted imaging (DWI) hippocampal hyperintensity. CONCLUSION: Our findings show
      that in a real-life clinical scenario, TEA is frequent but often overlooked.
      However, simple clinical data and widely available neurophysiological
      examinations can truly help to effectively distinguish TEA from TGA.

PMID- 30296665
TI  - A comparison of levetiracetam and phenobarbital for the treatment of neonatal
      seizures associated with hypoxic-ischemic encephalopathy.
AB  - PURPOSE: Seizures are common in term infants with hypoxic-ischemic encephalopathy
      (HIE) undergoing therapeutic hypothermia. Although phenobarbital (PHB) is
      generally considered first-line therapy, some centers have embraced third
      generation antiepileptic drugs (AEDs) such as levetiracetam (LEV) given the
      impression of comparable efficacy and superior tolerability. We set out to
      compare the efficacy of PHB and LEV in a large single-center cohort. METHODS: We
      retrospectively identified consecutive newborns with HIE who were monitored with
      continuous video-electroencephalogram (VEEG) for the duration of therapeutic
      hypothermia. After identification of seizures, infants were treated with PHB or
      LEV at the discretion of treating physicians. We assessed time to seizure freedom
      as a function of AED choice, with adjustment for HIE severity and initial seizure
      frequency using the Kaplan-Meier procedure and multivariate Cox proportional
      hazards regression. RESULTS: We identified 78 infants with HIE. Among 44 (56%)
      patients who had VEEG-confirmed seizures, 34 became seizure-free during
      monitoring, and the remaining 10 died. Initial treatment with LEV, in comparison
      with PHB, predicted a shorter interval to seizure freedom in a univariate
      analysis (Hazard ratio (HR) = 2.58, P = 0.007), even after adjustment for initial
      seizure frequency and an unbiased ad hoc measure of HIE severity (adjusted HR =
      2.57, P = 0.010). This effect was recapitulated in an analysis in which patients
      with treatment crossover were excluded. As expected, severity of HIE was an
      independent predictor of longer duration to seizure freedom (HR = 0.16, P <
      0.001) and remained a significant predictor after adjustment for initial seizure
      burden and treatment agent. CONCLUSION: Despite a relatively small sample size
      and retrospective design, this study suggests that LEV is a viable alternative to
      PHB in the treatment of neonatal seizures associated with HIE. A large-scale
      randomized controlled trial is needed to confirm these findings.

PMID- 30296667
TI  - Generation and characterization of two human induced pluripotent stem cell
      (hiPSC) lines homozygous for the Apolipoprotein e4 (APOE4) risk variant
      Alzheimer's disease (ASUi005-A) and healthy non-demented control (ASUi006-A).
AB  - Although the majority of late-onset Alzheimer's disease (AD) patients are labeled
      sporadic, multiple genetic risk variants have been identified, the most powerful
      and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene.
      Here, we generated human induced pluripotent stem cell (hiPSC) lines from the
      peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient
      [ASUi005-A] and a non-demented control (NDC) patient [ASUi006-A] homozygous for
      the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed
      pluripotency markers, exhibited a normal karyotype, and retained the ability to
      differentiate into cells representative of the three germ layers. Resource table.

PMID- 30296668
TI  - Generation of integration-free iPS cell lines from three sickle cell disease
      patients from the state of Bahia, Brazil.

PMID- 30296669
TI  - Generation of the induced pluripotent stem cell line UHOMi001-A from a patient
      with mutations in CCDC40 gene causing Primary Ciliary Dyskinesia (PCD).
AB  - Primary Ciliary Dyskinesia (PCD) is a rare heterogeneous genetic disorder
      affecting motile cilia structure and function leading to lung disease. We
      generated induced pluripotent stem cells (iPSCs) from dermal fibroblasts of a
      female PCD patient carrying disease-causing variants in the CCDC40 gene.
      Reprogramming was performed with the human OSKM transcription factors using the
      Sendai-virus delivery system. The resulting transgene free iPSCs had normal
      karyotype, expressed pluripotency markers, could differentiate into the three
      germ layers in vivo and retained the disease-causing CCDC40 mutations. This iPSC
      line could be useful to model PCD disease and test gene therapy strategies.
      Resource Table.

PMID- 30296666
TI  - Neurolinguistics Research Advancing Development of a Direct-Speech Brain-Computer
      Interface.
AB  - A direct-speech brain-computer interface (DS-BCI) acquires neural signals
      corresponding to imagined speech, then processes and decodes these signals to
      produce a linguistic output in the form of phonemes, words, or sentences. Recent
      research has shown the potential of neurolinguistics to enhance decoding
      approaches to imagined speech with the inclusion of semantics and phonology in
      experimental procedures. As neurolinguistics research findings are beginning to
      be incorporated within the scope of DS-BCI research, it is our view that a
      thorough understanding of imagined speech, and its relationship with overt
      speech, must be considered an integral feature of research in this field. With a
      focus on imagined speech, we provide a review of the most important
      neurolinguistics research informing the field of DS-BCI and suggest how this
      research may be utilized to improve current experimental protocols and decoding
      techniques. Our review of the literature supports a cross-disciplinary approach
      to DS-BCI research, in which neurolinguistics concepts and methods are utilized
      to aid development of a naturalistic mode of communication.

PMID- 30296670
TI  - Generation of an iPSC line of a patient with Angelman syndrome due to an
      imprinting defect.
AB  - Angelman syndrome (AS) is a neurodevelopmental disorder with leading symptoms of
      happy demeanor, intellectual disability, ataxia and seizures. AS can be caused by
      genetic and epigenetic aberrations, resulting in the absence of functional UBE3A
      protein in the brain. UBE3A is an imprinted gene, which is, in neurons of the
      brain, expressed exclusively from maternal chromosome 15. The generated iPSC line
      was derived from skin fibroblasts of a patient with AS, who, due to an imprinting
      defect, lacked DNA methylation at the chromosome 15 imprinting center, which
      controls maternal-specific expression of UBE3A. Resource table.

PMID- 30296671
TI  - Patellofemoral joint stress during incline and decline running.
AB  - OBJECTIVES: To compare patellofemoral joint (PFJ) stress between level, incline,
      and decline running. DESIGN: Experimental study. SETTING: University laboratory.
      PARTICIPANTS: Twenty recreational runners. MAIN OUTCOME MEASURES: Kinematics and
      kinetics of the trunk and lower extremity were obtained under 3 treadmill
      conditions: level, 6 degrees  incline, and 6 degrees  decline. PFJ stress, PFJ
      reaction force, and PFJ contact area were determined using a biomechanical model.
      One-way ANOVAs with repeated measures and post-hoc analyses were used to compare
      outcome variables across the 3 conditions. RESULTS: Peak PFJ stress and PFJ
      stress-time integral (cumulative PFJ stress over the stance phase) during decline
      running were significantly higher than during level and incline running. There
      was no difference in peak PFJ stress and PFJ stress-time integral between level
      and incline running. The increased peak PFJ stress during decline running was
      related to increased PFJ reaction force, resulting from a decrease in trunk
      flexion angle. CONCLUSIONS: Running on a decline treadmill resulted in higher
      peak PFJ stress and stress-time integral. Peak PFJ stress and PFJ stress-time
      integral were similar during level and incline running. Results from this study
      may be used to prevent excessive PFJ stress during decline running, by targeting
      a postural strategy utilizing increased trunk flexion.

PMID- 30296672
TI  - Reliability, validity, and minimal detectable change of Side Hop Test in male
      children and adolescents.
AB  - OBJECTIVE: To determine the reliability, measurement error, and construct
      validity of the Side Hop Test in male children and adolescents. DESIGN: Intra-and
      inter-rater reliability and construct validity study. SETTINGS: Soccer club.
      PARTICIPANTS: Thirty-six asymptomatic boys, 10-16 years old. MAIN OUTCOME: The
      intra and inter-rater reliability of the Side Hop Test were analyzed by
      Intraclass Correlation Coefficient (ICC), Standard Error of Measurement (SEM),
      and Minimum Detectable Change (MDC). The construct validity of the Side Hop Test
      in reference to the Single Hop Test, the Standing Long Jump Test, the Shuttle
      Run, and isometric muscle strength was analyzed. RESULTS: The intra-rater ICC of
      the Side Hop Test ranged from 0.63 to 0.67, SEM ranged from 1.2 to 2.5 s, and MDC
      ranged from 2.8 to 5.7 s. The inter-rater ICC ranged from 0.83 to 0.91, SEM
      ranged from 0.6 to 0.8 s, and MDC ranged from 1.4 to 1.9 s. The Side Hop Test was
      significantly correlated (p < 0.05) with the Single Hop Test (r = -0.49) and the
      Standing Long Jump (r = -0.47). CONCLUSION: The results support the use of the
      Side Hop Test to evaluate children and adolescents. The measurements showed good
      intra-rater and very good inter-rater reliability.

PMID- 30296673
TI  - Construction of multifunctional boron nitride nanosheet towards reducing toxic
      volatiles (CO and HCN) generation and fire hazard of thermoplastic polyurethane.
AB  - Considerable toxic volatiles (CO and HCN) generation and high fire hazard has
      definitely compromised the application of thermoplastic polyurethane (TPU). Here,
      a novel functionalization strategy for bulky h-BN is adopted to obtain the
      multifunctional CPBN, aiming at the flame retardancy reinforcement of TPU. The
      multifunctional CPBN is successfully prepared via the wrapping of phytic acid
      doped polypyrrole shell, following with the adsorption of copper ions. The
      obviously decreased peak heat release rate, peak smoke production rate and total
      smoke production values, obtained from cone test, confirms the reduced fire
      hazard of TPU composite with CPBN. The dramatic suppressions on CO and HCN
      releases can also be observed from TG-IR test. Tensile test demonstrates that
      adding CPBN favors the reinforcement in mechanical property of TPU. Thus, the
      concurrent improvements in flame retardancy and mechanical performance are
      achieved by incorporating CPBN. This work opens up new avenues for the
      functionalization of h-BN, and thus facilitates its promising applications in
      polymer-matrix composite.

PMID- 30296674
TI  - Phase transformation in the C form of myristic-acid crystals and DFT
      calculations.
AB  - In this study, the vibrational frequencies of myristic acid (CH3(CH2)12COOH) were
      obtained using density functional theory calculations, and the results were
      compared with experimental Raman and infrared data. Additionally, Raman spectra
      of crystalline myristic acid were recorded in the 300-20 K range. Raman
      spectroscopy gives important insights into the effect of low temperatures on its
      monoclinic phase. X-ray diffraction was performed from 298 to 133 K to provide
      additional information about the cryogenic behavior of the crystals. These
      undergo a phase transformation, which was confirmed by differential scanning
      calorimetry through an enthalpy anomaly observed at low temperatures. Raman
      spectra and X-ray diffraction refinement of the cell parameters in combination
      with differential scanning calorimetry at low temperatures revealed slight
      modifications, confirming a conformational change in the myristic acid molecules
      involving rearrangement of dimers within the unit cell.

PMID- 30296675
TI  - Identifying value-based quality indicators for general hospital psychiatry.
AB  - OBJECTIVE: To define generic quality indicators for general hospital psychiatry
      from the perspectives of patients, professionals (physicians, nurses, and
      managers), and payers (health insurance companies). METHODS: Quality variables
      were identified by reviewing the relevant literature. A working. group consisting
      of patients', professionals' and payers' representatives was mandated by their
      respective umbrella organizations. The working group prioritized the quality
      variables that were identified. Core values were defined and subsequently linked
      to preliminary quality indicators. These were tested for feasibility in ten
      hospitals in a four-week period. Stakeholder consultation took place by means of
      two invitational conferences and two written commentary rounds. RESULTS: Forty
      one quality variables were identified from the literature. After prioritization,
      seven core values were defined and translated to 22 preliminary indicators.
      Overall, the feasibility study showed high relevance scores and good
      implementability of the preliminary quality indicators. A final set of twenty-two
      quality indicators (17 structure, 3 process and 2 outcome indicators) was then
      established using a consensus-based approach. CONCLUSION: Consensus on a quality
      framework for general hospital psychiatry was built by incorporating the
      perspectives of relevant stakeholders. Results of the feasibility study suggest
      broad support and good implementability of the final quality indicators.
      Structural indicators were broadly defined, and process and outcome indicators
      are generic to facilitate quality measurement across settings. The quality
      indicator set can now be used to facilitate quality and outcome assessment,
      stimulate standardization of services, and help demonstrate (cost-)
      effectiveness.

PMID- 30296676
TI  - Increase in economic efficiency of water use caused by crop structure adjustment
      in arid areas.
AB  - The Heihe River is located in the arid zone of northwestern China. In its middle
      reach region, irrigation agriculture is well developed. With rapid population
      growth and expansion of the cultivated land in this region, effective water
      resource use is vital for the sustainable development of the river basin and the
      increase of incomes from farming practices. In this study, based on farmer survey
      data, the input parameters of the CROPWAT model were modified, the water use
      amount was simulated after deducting the influences of climate, seeds, and
      irrigation systems, and the variation of economic efficiency of water use (EEWU)
      induced by crop structure adjustment from 2001 to 2012 was analyzed. The results
      show that simulations for evapotranspiration of maize based on the CROPWAT model
      are in accord with the observed data. From 2001 to 2012, due to changes in the
      regional crop structure, EEWU in the study area increased by about 40%. In the
      arid areas in northwest China, crop structure adjustment has a huge potential for
      improving EEWU and increasing incomes from farming practices.

PMID- 30296677
TI  - Evaluating and supporting conservation action in agricultural landscapes of the
      Usumacinta River Basin.
AB  - There is increasing recognition that ecosystems and their services need to be
      managed at landscape scale and greater. The development of landscape-scale
      conservation strategies need to incorporate information from multiple sources. In
      this study, we combine various research tools to link landscape patterns with
      production units and systems in the Usumacinta River Basin, and inform the
      discussion of key questions around decision-making related to conservation action
      and policy in Southern Mexico. A typology based on policy-relevant farmer
      characteristics (land tenure, farm size, source of income, farming system)
      differentiated between farmers (traditional vs. cattle ranching) with different
      motivations that determine how management affects landscape configuration. Five
      main types of traditional farming systems were identified that combine different
      forms of land use and vary in their degree of land intensification. Major
      fragmentation and decrease in connectivity coincided spatially with floodplains
      dominated by large-scale commercial farms that specialize in livestock
      production. Traditional practices within large units with low-sloped high quality
      land were also seen to be intensive; however the presence of trees was notable
      throughout these units. Policies that promote livestock farming are among the
      principle causes motivating deforestation. Land intensification by traditional
      farmers decreased as the landscape became increasingly rugged. Traditional
      farmers are the focus of initiatives developed by the Biological Corridor project
      which seeks to increase forest cover and landscape connectivity. These
      initiatives have shown high levels of rural participation (10,010 farmers
      benefited from 27,778 projects involving 95,374 ha of land) and acceptance
      (producers carried out more than one project and several types of projects during
      the first eight years of work). Strong action is still required to take on the
      segment of large-scale ranchers. Changes in the structure of land tenure over the
      past decade are highlighted that could have a profound impact on conservation
      policies and programs.

PMID- 30296678
TI  - Oil spill cleanup employing magnetite nanoparticles and yeast-based magnetic
      bionanocomposite.
AB  - Oil spill is a serious environmental concern, and alternatives to remove oils
      from water involving biosorbents associated to nanoparticles is an emerging
      subject. Magnetite nanoparticles (MNP) and yeast magnetic bionanocomposite (YB
      MNP) composed by yeast biomass from the ethanol industry were produced,
      characterized, and tested to remove new motor oil (NMO), mixed used motor oil
      (MUMO) and Petroleum 28  degrees API (P28API) from water following the ASTM F726
      12 method, which was adapted by insertion of a lyophilization step to ensure the
      accuracy of the gravimetric approach. Temperature, contact time, the type and the
      amount of the magnetic material were the parameters evaluated employing a
      fractional factorial design. It was observed the removal of 89.0 +/- 2.6% or 3522
      +/- 118 g/kg (NMO) employing MNP; 69.1 +/- 6.2% or 2841 +/- 280 g/kg (MUMO) with
      YB-MNP; and 55.3 +/- 8.2% or 2157 +/- 281 g/kg (P28API) using MNP. The
      temperature was the most significant parameter in accordance with the Pareto's
      graphics (95% confidence) for all oil samples considered in this study as well as
      the two magnetic materials. Contact time and the interaction between the
      materials and temperature were also relevant. The D-Optimals designs showed that
      the NMO and P28API responded in a similar way for all evaluated parameters, while
      the uptake of MUMO was favored at higher temperatures. These behaviors
      demonstrate the influence of oil characteristics and the intermolecular forces
      between the oil molecules on the mechanism dragging process performed by the
      attraction between magnetite nanoparticles and a 0.7 T magnet. It was clear that
      this kind of experiment is predominantly a physic phenomenon which cannot be
      described as adsorption process.

PMID- 30296679
TI  - Navigating protected areas networks for improving diffusion of conservation
      practices.
AB  - The Natura 2000 protected area network is the cornerstone of European Union's
      biodiversity conservation strategy. These protected areas range across multiple
      biogeographic regions, and they include a diversity of species assemblages along
      with a diversity of managing organizations, altogether making difficult to pool
      relevant sites to facilitate the flow of knowledge significant to their
      management. Here we introduce an approach to navigating protected area networks
      that has the potential to foster systematic identification of key sites for
      facilitating the exchange of knowledge and diffusion of information within the
      network. To demonstrate our approach, we abstractly represented Romanian Natura
      2000 network as a co-occurrence network, with individual sites as nodes and
      shared species as edges, further combining into our analysis network topology,
      community detection, and network reduction methods. We identified most
      representative Natura 2000 sites that may increase the transfer of information
      within the national network of protected areas, detected clusters of sites and
      key sites for maintaining network cohesiveness, and highlighted the subsample of
      sites that retain the characteristics of the entire network. Our analysis
      provides implications for protected area prioritization by proposing a network
      perspective approach to collaboration rooted in ecological principles.

PMID- 30296680
TI  - Europe was a hub for the global spread of potato virus S in the 19th century.
AB  - Potato virus S (PVS) is a major plant pathogen that causes considerable losses in
      global potato production. Knowledge of the evolutionary history and spatio
      temporal dynamics of PVS is vital for developing sustainable management schemes.
      In this study, we investigated the phylodynamics of the virus by analysing 103
      nucleotide sequences of the coat protein gene, sampled between 1985 and 2014. Our
      Bayesian phylogenetic analyses showed that PVS has been evolving at a rate of
      3.32 * 10-4 substitutions/site/year (95% credibility interval 1.33 * 10-4-5.58 *
      10-4). We dated the crown group to the year 1325 CE (95% credibility interval 762
      1743 CE). Our phylogeographic analyses pointed to viral origins in South America
      and identified multiple migration pathways between Europe and other regions,
      suggesting that Europe has been a major hub for PVS transmission. The results of
      our study have potential implications for developing effective strategies for the
      control of this pathogen.

PMID- 30296681
TI  - Epithelial boost enhances antigen expression by vaccinia virus for the generation
      of potent CD8+ T cell-mediated antitumor immunity following DNA priming
      vaccination.
AB  - While both pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and TA-HPV recombinant
      vaccinia viral vector-based vaccines have elicited HPV-specific CD8+ T cell
      responses in HPV16/E7-expressing tumor models, and been used as prime-boost
      regimen to enhance HPV-specific immune responses in humans (NCT00788164), the
      optimal route of administration for TA-HPV remains unclear. In a preclinical
      model, we examined the immunogenicity of priming with intramuscular pNGVL4a
      Sig/E7(detox)/HSP70 followed by TA-HPV boost through different administration
      routes. We observed that priming twice with a pNGVL4a-Sig/E7(detox)/HSP70
      followed by a single TA-HPV immunization boost through skin scarification
      generated the strongest antigen-specific CD8+ T cell response in C57BL/6 mice.
      These data translate to tumor control and prolonged survival of treated mice. Our
      results provide rationale for future clinical testing of intramuscular pNGVL4a
      Sig/E7(detox)/HSP70 DNA vaccine prime, TA-HPV vaccine skin scarification boost
      immunization regimen for the control of HPV-associated diseases.

PMID- 30296682
TI  - Isolation and characterization of H5Nx highly pathogenic avian influenza viruses
      of clade 2.3.4.4 in Russia.
AB  - In 2016-2017, several subtypes of the highly pathogenic avian influenza (HPAI)
      virus were isolated on the territory of Russia. In the autumn of 2016, during the
      avian influenza virus surveillance in the territory of the Kamchatka region of
      Russia the HPAI A(H5N5) influenza virus was isolated. Then, during 2016-2017,
      multiple outbreaks among wild birds and poultry caused by HPAI A(H5N8) avian
      influenza virus were recorded in European part of Russia. At the end of 2017, an
      outbreak among poultry caused by HPAI A(H5N2) influenza virus was recorded in the
      European part of Russia. Phylogenetic analysis of HA of the A(H5N5), A(H5N8),
      A(H5N2) showed the strains belong to the clade 2.3.4.4 b. All isolated strains
      were antigenically closely related to candidate vaccine viruses of clade 2.3.4.4
      and showed high virulence in mice. Genetic analysis revealed presence of genetic
      markers potentially related to high virulence in mice in all studied viruses.

PMID- 30296683
TI  - Hemozoin inhibiting 2-phenylbenzimidazoles active against malaria parasites.
AB  - The 2-phenylbenzimidazole scaffold has recently been discovered to inhibit beta
      hematin (synthetic hemozoin) formation by high throughput screening. Here, a
      library of 325,728 N-4-(1H-benzo[d]imidazol-2-yl)aryl)benzamides was enumerated,
      and Bayesian statistics used to predict beta-hematin and Plasmodium falciparum
      growth inhibition. Filtering predicted inactives and compounds with negligible
      aqueous solubility reduced the library to 35,124. Further narrowing to compounds
      with terminal aryl ring substituents only, reduced the library to 18, 83% of
      which were found to inhibit beta-hematin formation <100 MUM and 50% parasite
      growth <2 MUM. Four compounds showed nanomolar parasite growth inhibition
      activities, no cross-resistance in a chloroquine resistant strain and low
      cytotoxicity. QSAR analysis showed a strong association of parasite growth
      inhibition with inhibition of beta-hematin formation and the most active compound
      inhibited hemozoin formation in P. falciparum, with consequent increasing
      exchangeable heme. Pioneering use of molecular docking for this system
      demonstrated predictive ability and could rationalize observed structure activity
      trends.

PMID- 30296684
TI  - Design, synthesis and biological evaluation of 1,4-Diazobicylco[3.2.2]nonane
      derivatives as alpha7-Nicotinic acetylcholine receptor PET/CT imaging agents and
      agonists for Alzheimer's disease.
AB  - alpha7-Nicotinic acetylcholine receptor (alpha7-nAChR) agonists are promising
      therapeutic drug candidates for treating the cognitive impairment associated with
      Alzheimer's disease (AD). Thus, a novel class of derivatives of 1,4
      diazobicylco[3.2.2]nonane has been synthesized and evaluated as alpha7-nAChR
      ligands. Five of them displayed high binding affinity (Ki = 0.001-25 nM). In
      particular, the Ki of 14 was 0.0069 nM, which is superior to that of the most
      potent ligand that was previously reported by an order of magnitude. Four of them
      had high selectivity for alpha7-nAChRs over alpha4beta2-nAChRs and no significant
      hERG (human ether-a-go-go-related gene) inhibition. Their agonist activity was
      also discussed preliminarily. One of the compounds, 15 (Ki = 2.98 +/- 1.41 nM),
      was further radiolabeled with 18F to afford [18F]15 for PET imaging, which
      exhibited high initial brain uptake (11.60 +/- 0.14%ID/g at 15 min post
      injection), brain/blood value (9.57 at 30 min post injection), specific labeling
      of alpha7-nAChRs and fast clearance from the brain. Blocking studies demonstrated
      that [18F]15 was alpha7-nAChR selective. In addition, micro-PET/CT imaging in
      normal rats further indicated that [18F]15 had obvious accumulation in the brain.
      Therefore, [18F]15 was proved to be a potential PET radiotracer for alpha7-nAChR
      imaging.

PMID- 30296685
TI  - Design, synthesis, and biological evaluation of novel pan agonists of FFA1,
      PPARgamma and PPARdelta.
AB  - The free fatty acid receptor 1 (FFA1) and peroxisome proliferator-activated
      receptors (PPARs) have attracted interest as potent targets for the treatment of
      metabolic syndrome such as type 2 diabetes. Based on the hypothesis that the dual
      agonists of PPARs and FFA1 would act as insulin sensitizers and secretagogues by
      simultaneous activation of PPARs and FFA1, we developed the design strategy to
      obtain dual PPARs/FFA1 agonist by hybrid FFA1 agonist 1 with PPARdelta agonist 2
      in consideration of their structural similarity. As expected, systematic
      exploration of structure-activity relationship and molecular modeling, results in
      the discovery of lead compound 15, a pan agonist with relative balanced
      activities between FFA1, PPARgamma and PPARdelta. The dose-response relationship
      studies suggested that the pan agonist 15 suppressed the excursion of blood
      glucose levels in a dose-dependent manner. During a 5-days treatment in ob/ob
      mice, the pan agonist 15 (100 mg/kg) revealed sustained hypoglycemic effect, even
      proximity to the most advanced FFA1 agonist (TAK-875, 40 mg/kg), which might be
      attributed to its pan PPARs/FFA1 activities to simultaneous regulate the
      mechanism of insulin secretion and resistance. These positive results suggest
      that the dual PPARs/FFA1 agonists such as lead compound 15 might be novel
      therapeutic strategy to modulate the complex pathological mechanisms of type 2
      diabetes.

PMID- 30296686
TI  - Design, synthesis and anti-mycobacterial activity evaluation of benzofuran-isatin
      hybrids.
AB  - Herein we report the design and synthesis of a series of novel benzofuran-isatin
      hybrids, and in vitro evaluation of their anti-mycobacterial activity against
      both drug-susceptible and multi-drug resistant (MDR) Mycobacterium tuberculosis
      (MTB) strains. In parallel, cytotoxicity of these hybrids was also tested in VERO
      cells. Preliminary results indicated that all hybrids with acceptable
      cytotoxicity in VERO cells (CC50: 128->1024 MUg/mL) exhibited considerable anti
      mycobacterial activities against MTB H37Rv and MDR-TB with MIC ranging from 0.25
      to 8 MUg/mL. It is worth noting that hybrid 8f with no cytotoxicity towards VERO
      cells (CC50: >1024 MUg/mL) was found to be the most active compound (MIC: 0.25
      and 0.5 MUg/mL) against MTB H37Rv and MDR-TB strains. Comparing to the first-line
      anti-tuberculosis agents rifampicin and isoniazid, hybrid 8f has shown over two
      magnitude more active against MDR-TB. The hybrid 8f was further evaluated for its
      metabolic stability and in vivo pharmacokinetic profiles, with the results
      showing that hybrid 8f exhibited lower metabolic stability compared to inhibitor
      TAM16. Further modification based on hybrid 8f is needed to improve the metabolic
      stability and pharmacokinetic profiles.

PMID- 30296687
TI  - Hybrid compounds from chalcone and 1,2-benzothiazine pharmacophores as selective
      inhibitors of alkaline phosphatase isozymes.
AB  - Chalcones and 1,2-benzothiazines are two important classes of bioactive
      compounds, each scaffold endowed with diverse pharmacological activities.
      Combining both of these pharmacophores in a single molecule was aimed to yield
      multi-modal agents. Herein, we report a series of hybrid compounds 3a-3o derived
      from chalcones and 1,2-benzothiazine cores. They were synthesized from
      commercially available sodium saccharin, and the resulting 1,2-benzothiazine
      derived ketone was then condensed with aromatic aldehydes in an aldol
      condensation to obtain the respective chalcones. The compounds were characterized
      using different analytical techniques including FT-IR, NMR spectroscopy, mass
      spectrometry and X-ray crystallography. Some synthesized chalcones revealed
      potent and/or selective inhibitory properties towards alkaline phosphatase
      isozymes transiently expressed in COS-7 cells. A detailed structure-activity and
      selectivity study was carried out with regard to the effect of different
      substituents at ortho-, meta- and para-positions of the phenyl residue. Compound
      3c was the most effective human intestinal alkaline phosphatase (h-IAP) inhibitor
      (IC50 value of 1.04 MUM), while it was not active against human tissue non
      specific alkaline phosphatase (h-TNAP) isozyme. In contrast, 3i was a selective
      inhibitor of h-TNAP with IC50 values of 0.25 +/- 0.01 MUM. The possible binding
      interactions of the most effective inhibitors of h-TNAP and h-IAP were obtained
      from molecular docking studies.

PMID- 30296688
TI  - Novel potential pyrazolopyrimidine based translocator protein ligands for the
      evaluation of neuroinflammation with PET.
AB  - Translocator protein (TSPO) is an interesting biological target because TSPO
      overexpression is associated with microglial activation caused by neuronal damage
      or neuroinflammation, and these activated microglia are involved in several
      central nervous system diseases. Herein, novel fluorinated ligands (14a-c and 16a
      c) based on a 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide scaffold were
      synthesized, and in vitro characterization of each of the novel ligands was
      performed to elucidate structure activity relationships. All of the newly
      synthesized ligands displayed nano-molar affinity for TSPO. Particularly, an in
      vitro affinity study suggests that 2-(5,7-diethyl-2-(4-(3-fluoro-2
      methylpropoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide (14a),
      which exhibited high nano-molar affinity for TSPO and proper lipophilicity, was
      suitable for in vivo brain studies. Thus, radiosynthesis from tosylate precursor
      13a using fluorine-18 was performed, and [18F]14a was obtained in a 31%
      radiochemical yield (decay-corrected). Dynamic positron emission tomography (PET)
      imaging studies were performed in a lipopolysaccharide (LPS)-induced
      neuroinflammation rat model using [18F]14a to identify the location of
      inflammation in the brain with a high target-to-background signal ratio. In
      addition, we validated that the locations of inflammatory lesions found by PET
      imaging were consistent with the locations observed by histological examination
      of dissected brains using antibodies. These results suggest that [18F]14a is a
      novel promising PET imaging agent for diagnosing neuroinflammation, and it may
      also prove to be applicable for diagnosing other diseases, including cancers
      associated with altered TSPO expression, using PET techniques.

PMID- 30296689
TI  - 137Cs and K annual fluxes in a cropland and forest ecosystems twenty-four years
      after the Chernobyl accident.
AB  - Biological cycles of the Chernobyl originated cesium-137 (137Cs, radiocesium) and
      the natural potassium (K) in oak, birch, and pine forest, and wheat cropland in
      Russian Federation, approximately 500 km northeast of the Chernobyl Nuclear Power
      Plant, were subject to a multiyear monitoring. By 2010, the annual return of
      137Cs from forest vegetation to the soil in dead tree components still exceeds
      its annual accumulation in the tree phytomass by a factor of 4-6, apparently due
      to residual surface contamination in the external bark and the ongoing process of
      tree stand decontamination following the initial fallout. In the cropland, both
      ascending and descending fluxes of 137Cs are close to the steady state. The
      annual accumulation of 137Cs in the tree biomass was the highest in the oak
      forest and the lowest in the pine forest. The annual K accumulation was the
      highest in the cropland and the lowest in the pine forest.

PMID- 30296690
TI  - Metal regulation of metabolism.
AB  - A broad range of biochemicals, from proteins to nucleic acids, function properly
      only when associated with a metal, usually a divalent cation. Not any divalent
      metal will do: these metals differ in their ionic radius, dissociation in water,
      ionization potential, and number of unpaired electrons in their outer shells, and
      so substituting one metal for another often changes substrate positioning, redox
      reactivities, and physiological performance, and thus may serve as a regulatory
      mechanism. For instance, exchanging manganese for magnesium in several
      chloroplast enzymes maintains plant carbon-nitrogen balance under rising
      atmospheric CO2 concentrations. Here, we review this and a few other cases where
      association of proteins or nucleic acids with different metals control
      metabolism.

PMID- 30296691
TI  - An analysis of the nutrition status of neighboring Indigenous and non-Indigenous
      populations in Kanungu District, southwestern Uganda: Close proximity, distant
      health realities.
AB  - OBJECTIVES: Malnutrition is a persistent health concern throughout the world.
      Globally, Indigenous peoples experience poorer health outcomes compared to their
      non-Indigenous neighbours. Despite this, malnutrition among Indigenous
      populations is poorly understood. This analysis estimated the prevalence, and
      modeled possible determinants of, moderate acute malnutrition (MAM) and severe
      acute malnutrition (SAM) for Indigenous Batwa and non-Indigenous Bakiga of
      Kanungu District in Southwestern Uganda. We then characterize possible mechanisms
      driving differences in malnutrition. METHODS: Retrospective cross-sectional
      surveys were administered to 10 Batwa communities and 10 matched Bakiga Local
      Councils during April of 2014 (n = 1167). Individuals were classified as MAM and
      SAM based on middle upper-arm circumference (MUAC) for their age-sex strata.
      Mixed-effects regression models quantified the variation in malnutrition
      occurrence, considering individual, household, and community-ethnicity level
      effects. Models controlled for age, sex, number of dependents, education, and
      relative wealth. RESULTS: Malnutrition is high among Batwa children and adults,
      with nearly half of Batwa adults (45.34%, 95% CI 34.82 to 55.86 for males;
      45.86%, 95% CI 37.39 to 54.33 for females) and nearly a quarter of Batwa children
      (20.31%, 95% CI 13.07 to 26.93 for males; 25.81%, 95% CI 17.56 to 32.84 for
      females) meeting MAM criteria. SAM prevalence is lower than MAM prevalence, with
      SAM highest among adult Batwa males (11.60%, 95% CI 4.83 to 18.37) and adult
      Batwa females (3.00%, 95% CI 0.10 to 5.90). SAM prevalence among children was
      higher for Batwa males (7.03%, 95% CI 1.36 to 12.70) compared to Bakiga males
      (0.57%, 95% CI 0 to 1.69). Models that incorporated community ethnicity explained
      the greatest variance (>60%) in MUAC values. CONCLUSION: This research
      demonstrates a malnutrition inequality between the Indigenous Batwa and non
      Indigenous Bakiga of Kanungu District, Uganda, with model results suggesting
      further investigation into the role of ethnicity as an upstream social
      determinant of health.

PMID- 30296693
TI  - The effect of job loss on pharmaceutical prescriptions.
AB  - We estimate the effect of job loss on the probability that long-tenured workers
      are prescribed anti-hypertensive and psychotropic drugs. We exploit two
      administrative data sources from the Veneto region in Italy and estimate an event
      study model. Our results indicate that the probability of drug prescription
      increases among under-40 males but not among older males or female workers. We
      suggest that the effect on younger male workers is the combined result of their
      typical role as breadwinners, limited wealth buffers in case of layoff, and
      unfavourable employment legislative protection.

PMID- 30296692
TI  - Association between family members and risk of postpartum depression in Japan:
      Does "who they live with" matter? -The Japan environment and Children's study.
AB  - There are many psychosocial and biomedical risk factors for postpartum depression
      (PPD). However, associations between co-resident family members and PPD risk have
      not been examined. This study investigated whether co-resident family members
      were associated with risk for PPD during 1 month postpartum among Japanese women,
      and if these associations were modified by household income and their perceived
      partner's involvement in childcare. The sample comprised 86,490 women. Data were
      drawn from the Japan Environment and Children's Study, a large-scale national
      cohort study started in 2011. Our major predictor was co-resident family members
      when they registered around the first trimester of the women's pregnancy:
      partner, parent(s), parent(s)-in-law, or child(ren). The outcome was PPD at 1
      month after delivery, assessed by the Edinburgh Postnatal Depression Scale.
      Adjusted odds ratios (OR) for family members and PPD incidence were calculated
      using multivariable logistic regression analysis. Subgroup analyses were
      conducted by household income and perceived partner's involvement in childcare.
      Adjusted ORs (95% confidence interval) for PPD for those not living with their
      partner, parent(s), parent(s)-in-law, or child(ren) compared with those who lived
      with these family members were 1.21 (1.07-1.37), 1.13 (1.03-1.24), 0.91 (0.84
      0.98), and 1.42 (1.31-1.53), respectively. The level of perceived partner's
      involvement in childcare changed the identified association between family member
      and PPD. We found that "who a pregnant woman lives with" affects the risk of PPD
      in the first month postpartum, and high levels of perceived partner's involvement
      in childcare reduced harmful effects/increased protective effect of family
      members on PPD incidence. These findings suggested that interventions to increase
      perceived partner's support for childcare may be effective in preventing PPD,
      regardless of living situation.

PMID- 30296694
TI  - Long-term effects of disaster on depressive symptoms: Type of exposure matters.
AB  - RATIONALE: Natural disasters have the potential to change the lives of older
      people, yet most studies rely on small convenience samples, few include
      assessments of people prior to the disaster, and only a handful examine the
      effects of different types of exposure. OBJECTIVE: Our analyses add new knowledge
      to the literature by examining the ways in which four types of exposure (i.e.,
      geographic, peri-traumatic stress, personal and property loss, and post-storm
      hardship) affect depressive symptoms experienced by older people over a five-year
      period. METHOD: We analyzed four waves of data from the ORANJ BOWL panel using
      multilevel mixed effects models. RESULTS: We found that although each type of
      exposure had an independent effect on depressive symptoms, the effects of peri
      traumatic stress were dominant. CONCLUSIONS: As nearly 20% of people in the
      United States will experience a natural disaster during the course of their
      lives, it is critical to understand how disaster exposure can influence mental
      health because each type of exposure demands a different response. Finding that
      an individual's emotional response during the disaster plays an important role in
      the development of depressive symptoms suggests that reduction of exposure to
      traumatic stress during a storm (i.e., evacuation from a storm area) is important
      for older people. Likewise, immediate interventions following a disaster that
      target people experiencing high levels of peri-traumatic distress may be
      particularly effective and that failing to attend to these people may miss a
      critical opportunity and result in years of suffering.

PMID- 30296695
TI  - Prenatal exposure to air pollution and intergenerational economic mobility:
      Evidence from U.S. county birth cohorts.
AB  - New estimates reveal intergenerational economic mobility varies substantially
      across U.S. counties. The potential role of local environmental health exposures
      in structuring mobility outcomes has been thus far unexamined, despite mounting
      evidence that early life exposure to environmental pollutants has lasting impacts
      for individual human capital development and labor market performance. This study
      aims to fill this gap by estimating the impact of exposure to air pollution in
      the birth year on the average intergenerational mobility outcomes of children
      from low-income families as measured in adulthood. We do so by linking measures
      of intergenerational economic mobility for U.S. county-cohorts born between 1980
      and 1986 to the county average concentration of total suspended particulates
      (TSP) in the birth year. We then estimate multivariate linear regression models
      that adjust for birth-cohort fixed effects, county-fixed effects and time-varying
      county-level covariates to address potential confounding. We find higher levels
      of TSP in birth year is associated with less upward economic mobility for
      children from low-income families: a one standard deviation increase in TSP
      levels is associated with a 0.14 point reduction in average income percentile
      ranking as measured in adulthood. Notably, we find no association for children
      from high income families. Our findings indicate early life exposure to air
      pollution may reduce the prospects children from low-income families will achieve
      upward economic mobility and suggest variation in environmental quality may help
      explain observed variation in mobility outcomes.

PMID- 30296697
TI  - Dose-related impacts of imidacloprid oral intoxication on brain and liver of rock
      pigeon (Columba livia domestica), residues analysis in different organs.
AB  - Available data regarding Imidacloprid (IMI) insecticide hazards to birds are
      still being scare. Our study aimed to investigate toxic impacts of IMI oral
      gavage by different dose levels on the brain and liver of Rock pigeon (Columba
      livia domestica). Forty mature male birds were divided equally into four groups.
      A control group (C) was orally dosed Mazola corn oil and other three groups; the
      low dose (LD), the medium dose (MD), and the high dose (HD) groups were orally
      dosed IMI in Mazola corn oil by three dose levels corresponding to 1/15th,
      1/10th, 1/5th IMI oral LD50 respectively. IMI exposure induced a significant
      decrease in serum levels of glutathione (GSH), superoxide dismutase (SOD) enzyme
      activity. On the other hand; malondialdehyde (MDA) levels were elevated. The
      levels of serum total protein, albumin, globulin, and A/G ratio showed a non
      significant changes in all IMI dosed groups except levels of total protein in the
      HD IMI dosed group showed a significant decrease compared to the C group. Serum
      levels of alanine aminotransferase (ALT), lactate dehydrogenase (LDH), uric acid,
      plasma tumor necrosis factor alpha (TNFalpha) and plasma acetylcholinesterase
      (AChEs) enzyme activities showed a significant dose related increase in all IMI
      exposed groups compared to the C group; except the levels of ALT, LDH, and uric
      acid showed a non significant decrease in the LD IMI dosed group only. Residues
      of IMI were detected in the pectoral muscles, liver, brain, and kidney of all
      dosed rock pigeon. Moreover; pectoral muscles were the highest tissue for IMI
      residues detection. This is the first study reports accumulation of IMI in
      tissues other than crop, liver, and kidney of rock pigeon including brain and
      muscles. Moreover, the examined brain and liver tissues of all IMI dosed groups
      showed dosed related alterations in their structural and ultra-structural
      morphology. It is concluded that IMI oral administration to pigeon induced
      oxidative stress and detrimental effects in brain and liver of exposed pigeons.
      Additionally; IMI bio-accumulated in different organs being muscles is the
      highest tissues for IMI residues, thus monitoring of IMI residues in food is very
      essential.

PMID- 30296696
TI  - Repurposing enzymatic transferase reactions for targeted labeling and analysis of
      DNA and RNA.
AB  - Produced as linear biopolymers from four major types of building blocks, DNA and
      RNA are further furnished with a range of covalent modifications. Despite the
      impressive specificity of natural enzymes, the transferred groups are often poor
      reporters and not amenable to further derivatization. Therefore, strategies based
      on repurposing some of these enzymatic reactions to accept derivatized versions
      of the transferrable groups have been exploited. By far the most widely used are
      S-adenosylmethionine-dependent methyltransferases, which along with several other
      nucleic acids modifying enzymes offer a broad selection of tagging chemistries
      and molecular features on DNA and RNA that can be targeted in vitro and in vivo.
      Engineered enzymatic reactions have been implemented in validated DNA sequencing
      based protocols for epigenome analysis. The utility of chemo-enzymatic labeling
      is further enhanced with recent advances in physical detection of individual
      reporter groups on DNA using super resolution microscopy and nanopore sensing
      enabling single-molecule multiplex analysis of genetic and epigenetic marks in
      minute samples. Altogether, a number of new powerful techniques are currently in
      use or on the verge of real benchtop applications as research tools or next
      generation diagnostics.

PMID- 30296698
TI  - Toxicity and cytotoxicity of the insecticide imidacloprid in the midgut of the
      predatory bug, Podisus nigrispinus.
AB  - The selectivity of insecticides on natural enemies in pest control are an
      important strategy for Integrated Pest Management. However, insecticides can have
      side effects on non-target organisms such as natural enemies. This study
      evaluated the histological and cytological changes mediated by the sublethal
      concentration of the imidacloprid insecticide on the midgut of non-target
      predator Podisus nigrispinus (Heteroptera: Pentatomidae), used in the biological
      control of pests. Imidacloprid was toxic for P. nigrispinus with LC50 = 3.75 mg L
      1 and survival of 51.8%. This sublethal concentration of imidacloprid causes
      histological alterations in the midgut epithelium and cytotoxic features were
      irregular border epithelium, cytoplasmic vacuolation, and apocrine secretions in
      the first 6 h after exposure with the insecticide. Apoptosis in the digestive
      cells occurs after 12 h of exposure in the midgut. These results suggest that
      imidacloprid may affect the digestive physiology of P. nigrispinus and compromise
      the effective predation of this insect a biological control agent. The associated
      use of this insecticide with the predator in pest control should be carefully
      evaluated.

PMID- 30296699
TI  - Restoration of SERCA ATPase prevents oxidative stress-related muscle atrophy and
      weakness.
AB  - Molecular targets to reduce muscle weakness and atrophy due to oxidative stress
      have been elusive. Here we show that activation of Sarcoplasmic Reticulum (SR)
      Ca2+ ATPase (SERCA) with CDN1163, a novel small molecule allosteric SERCA
      activator, ameliorates the muscle impairment in the CuZnSOD deficient (Sod1-/-)
      mouse model of oxidative stress. Sod1-/- mice are characterized by reduced SERCA
      activity, muscle weakness and atrophy, increased oxidative stress and
      mitochondrial dysfunction. Seven weeks of CDN1163 treatment completely restored
      SERCA activity and reversed the 23% reduction in gastrocnemius mass and 22%
      reduction in specific force in untreated Sod1-/- versus wild type mice. These
      changes were accompanied by restoration of autophagy protein markers to the
      levels found in wild-type mice. CDN1163 also reversed the increase in
      mitochondrial ROS generation and oxidative damage in muscle tissue from Sod1-/-
      mice. Taken together our findings suggest that the pharmacological restoration of
      SERCA is a promising therapeutic approach to counter oxidative stress-associated
      muscle impairment.

PMID- 30296700
TI  - AVE 0991 attenuates oxidative stress and neuronal apoptosis via Mas/PKA/CREB/UCP
      2 pathway after subarachnoid hemorrhage in rats.
AB  - Oxidative stress and neuronal apoptosis have been demonstrated to be key features
      in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Previous studies
      have indicated that Mas receptor activation initiates an anti-oxidative and anti
      apoptotic role in the brain. However, whether Mas activation can attenuate
      oxidative stress and neuronal apoptosis after SAH remains unknown. To investigate
      the beneficial effect of Mas on oxidative stress injury and neuronal apoptosis
      induced by SAH, a total of 196 rats were subjected to an endovascular perforation
      model of SAH. AVE 0991 (AVE), a selective agonist of Mas, was administered
      intranasally 1 h after SAH induction. A779, a selective inhibitor of Mas, and
      small interfering ribonucleic acid (siRNA) for UCP-2 were administered by
      intracerebroventricular (i.c.v) injection at 1 h and 48 h before SAH induction
      respectively. Neurological tests, immunofluorescence, TUNEL, Fluoro-Jade C, DHE
      staining, and Western blot experiments were performed. We found that Mas
      activation with AVE significantly improved neurobehavioral scores and reduced
      oxidative stress and neuronal apoptosis in SAH+AVE group compared with
      SAH+vehicle group. Moreover, AVE treatment significantly promoted phosphorylation
      of CREB and the expression UCP-2, as well as upregulated expression of Bcl-2 and
      downregulation of Romo-1 and Bax. The protective effects of AVE were reversed by
      i.c.v injection of A779 and UCP-2 siRNA in SAH+AVE+A779 and SAH+AVE+UCP-2 siRNA
      groups, respectively. In conclusion, our data provides evidence that Mas
      activation with AVE reduces oxidative stress injury and neuronal apoptosis
      through Mas/PKA/p-CREB/UCP-2 pathway after SAH. Furthermore, our study indicates
      that Mas may be a novel therapeutic treatment target in early brain injury of
      SAH.

PMID- 30296703
TI  - Suitability of developed composite materials for meniscal replacement:
      Mechanical, friction and wear evaluation.
AB  - The meniscus is a complex and frequently damaged tissue which requires a
      substitute capable of reproducing similar biomechanical functions. This study
      aims to develop  a synthetic meniscal substitute that can mimic the function of
      the native meniscus. Medical grade silicones reinforced with nylon were
      fabricated using compression moulding and evaluated for mechanical and
      tribological properties. The optimal properties were obtained with tensile
      modulus increased considerably from 10.7 +/- 2.9 MPa to 114.6 +/- 20.9 MPa while
      compressive modulus was found to reduce from 2.5 +/- 0.6 MPa to 0.7 +/- 0.3 MPa.
      Using a tribometer, the coefficient of friction of 0.08 +/- 0.02 was measured at
      the end of the 100,000 cycles. The developed composite could be an auspicious
      substitute for the native meniscus and the knowledge gained from this study is
      useful as it enhances the understanding of a potentially suitable material for
      meniscal implants.

PMID- 30296701
TI  - Fenofibrate improves vascular endothelial function and contractility in diabetic
      mice.
AB  - Fenofibrate, a peroxisome proliferator-activated receptors alpha (PPARalpha)
      agonist, reduces vascular complications of diabetic patients but its protective
      mechanisms are not fully understood. Here we tested the hypothesis that
      fenofibrate improves vascular endothelial dysfunction by balancing endothelium
      dependent relaxation and contractility of the aorta in diabetes mellitus (DM). In
      streptozotocin-induced diabetic mice, eight weeks of fenofibrate treatment (100
      mg/Kg/d) improved endothelium dependent relaxation in the macro- and
      microvessels, increased nitric oxide (NO) levels, reduced renal damage markers
      and effects of the vasoconstrictor prostaglandin. Levels of superoxide dismutase
      and catalase were both reduced and hydrogen peroxide was increased in vehicle
      treated DM, but these changes were reversed by fenofibrate treatment.
      Vasodilation of the aorta after fenofibrate treatment was reversed by PPARalpha
      or AMPKalpha inhibitors. Western blots showed that fenofibrate treatment elevated
      PPARalpha expression, induced liver kinase B1 (LKB1) translocation from the
      nucleus to the cytoplasm and activated AMP-activated protein kinase-alpha
      (AMPKalpha), thus activating endothelial NO synthase (eNOS). Also, fenofibrate
      treatment decreased NF-kappaB p65 and cyclooxygenase 2 proteins in aortas.
      Finally, incubation with indomethacin in vitro improved aortic contractility in
      diabetic mice. Overall, our results show that fenofibrate treatment in diabetic
      mice normalizes endothelial function by balancing vascular reactivity via
      increasing NO production and suppressing the vasoconstrictor prostaglandin,
      suggesting mechanism of action of fenofibrate in mediating diabetic vascular
      complications.

PMID- 30296702
TI  - Persistent increase in mitochondrial superoxide mediates cisplatin-induced
      chronic kidney disease.
AB  - Severe and recurrent cisplatin-induced acute kidney injury (AKI) as part of
      standard cancer therapy is a known risk factor for development of chronic kidney
      disease (CKD). The specific role of superoxide (O2*-)-mediated disruption of
      mitochondrial oxidative metabolism in CKD after cisplatin treatment is
      unexplored. Cisplatin is typically administered in weekly or tri-weekly cycles as
      part of standard cancer therapy. To investigate the role of O2*- in predisposing
      patients to future renal injury and in CKD, mice were treated with cisplatin and
      a mitochondrial-specific, superoxide dismutase (SOD) mimetic, GC4419. Renal
      function, biomarkers of oxidative stress, mitochondrial oxidative metabolism, and
      kidney injury markers, as well as renal histology, were assessed to evaluate the
      cellular changes that occur one week and one month (CKD phase) after the
      cisplatin insult. Cisplatin treatment resulted in persistent upregulation of
      kidney injury markers, increased steady-state levels of O2*-, increased O2*-
      mediated renal tubules damage, and upregulation of mitochondrial electron
      transport chain (ETC) complex I activity both one week and one month following
      cisplatin treatment. Treatment with a novel, clinically relevant, small-molecule
      superoxide dismutase (SOD) mimetic, GC4419, restored mitochondrial ETC complex I
      activity to control levels without affecting complexes II-IV activity, as well as
      ameliorated cisplatin-induced kidney injury. These data support the hypothesis
      that increased mitochondrial O2*- following cisplatin administration, as a result
      of disruptions of mitochondrial metabolism, may be an important contributor to
      both AKI and CKD progression.

PMID- 30296704
TI  - Mechanical properties and cytotoxicity of hierarchical carbon fiber-reinforced
      poly (ether-ether-ketone) composites used as implant materials.
AB  - Weak mechanical properties affect the application of PEEK as an implant. Carbon
      fiber (CFR) reinforcement provides an excellent solution to improve the
      mechanical strength of PEEK and to provide perfect matching of elastic modulus
      between CFR-PEEK composites and human bone. To investigate the effect of carbon
      fiber content on the mechanical, thermal properties and cytotoxicity of CFR
      reinforced PEEK composites, a series of CFR-PEEK composites with different carbon
      fiber content (25 wt%, 30 wt%, 35 wt%, 40 wt%) was prepared in this work. Thermal
      decomposition behavior and melting temperature were studied by thermogravimetric
      analysis (TGA) and differential scanning calorimetry (DSC), respectively.
      Subsequently, mechanical properties including bending strength, compressive
      strength, impact strength and hardness were tested respectively. Afterwards, the
      fracture morphology of the bending test samples was observed by scanning electron
      microscopy (SEM). In addition, murine fibroblast L929 cells were adopted for
      cytotoxicity test by CCK-8 assay in vitro, and the morphology of cells was
      observed by inverted fluorescence microscope simultaneously, cell compatibility
      of CFR-PEEK composites was tested.

PMID- 30296705
TI  - Current evolutionary adaptiveness of anxiety: Extreme phenotypes of anxiety
      predict increased fertility across multiple generations.
AB  - OBJECTIVE: Although recent research has begun to examine the impact of elevated
      anxiety on evolutionary fitness, no prior research has examined anxiety across a
      continuum. Such research is important as the effect of traits across a continuum
      on fertility hold important implications for the levels and distribution of the
      traits in later generations. METHOD: In a three-generational sample (N = 2657)
      the linear and quadratic relationship between anxiety and the number of children,
      grandchildren, and great-grandchildren 15 years later was examined. RESULTS: The
      findings suggested that anxiety had a positive quadratic relationship with the
      number of children, grandchildren, and great-grandchildren 15 years later. These
      relationships were not significantly moderated by sex. Moreover, most of the
      variance between anxiety and the number of great-grandchildren was explained by
      anxiety's influence on the number of children and grandchildren, as opposed to
      anxiety having an independent direct impact on the number of great-grandchildren.
      CONCLUSION: These findings suggest that extreme values from the mean anxiety are
      associated with increased evolutionary fitness within the modern environment.

PMID- 30296706
TI  - Sex differences during emotion processing are dependent on the menstrual cycle
      phase.
AB  - Sex differences in the neural processing of emotion are of special interest
      considering that mood and anxiety disorders predominant in females. However,
      these sex-related differences were typically studied without considering the
      hormonal status of female subjects, although emotion processing in the brain was
      shown to differ between phases of the menstrual cycle. In this functional MRI
      study, we demonstrated the influence of the menstrual cycle phase on sex
      differences in brain activity and functional connectivity during negative and
      positive emotions, using two different paradigms: emotion perception and emotion
      experience. Twenty naturally cycling healthy women without premenstrual symptoms
      were scanned twice: during the mid-follicular and late-luteal menstrual phases,
      and compared to a matched group of twenty healthy men. During negative emotion
      perception, men showed increased neural activity in the right hippocampal
      formation relative to women in the mid-follicular phase, and increased activity
      in the right cerebellum relative to women in the late-luteal phase. During
      experience of amusement, reduced putamen-ventrolateral prefrontal cortex and
      putamen-dorsomedial prefrontal cortex functional connectivity were observed for
      women in the late-luteal phase relative to men and associated with levels of sex
      hormones. These neural and hormonal findings were complemented by behavioral
      reports of reduced amusement and increased sadness in late-luteal women. Our
      results demonstrate menstrual phase-dependent sex differences in emotion
      perception and experience and may suggest a biological tendency for a deficient
      experience of pleasure and reward during the late-luteal phase. These findings
      may further shed light on the underlying pathophysiology of premenstrual
      dysphoric disorder.

PMID- 30296707
TI  - Tissue-specific localization of polyketide synthase and other associated genes in
      the lichen, Cladonia rangiferina, using laser microdissection.
AB  - The biosynthesis of two polyketides, atranorin and fumarprotocetraric acid,
      produced from a lichen-forming fungus, Cladonia rangiferina (L.) F. H. Wigg. was
      correlated with the expression of eight fungal genes (CrPKS1, CrPKS3, CrPKS16,
      Catalase (CAT), Sugar Transporter (MFsug), Dioxygenase (YQE1), C2H2 Transcription
      factor (C2H2), Transcription Factor PacC (PacC), which are thought to be involved
      in polyketide biosynthesis, and one algal gene, NAD-dependent deacetylase sirtuin
      2 (AsNAD)), using laser microdissection (LMD). The differential gene expression
      levels within the thallus tissue layers demonstrate that the most active region
      for potential polyketide biosynthesis within the lichen is the outer apical
      region proximal to the photobiont but some expression also occurs in reproductive
      tissue. This is the first study using laser microdissection to explore gene
      expression of these nine genes and their location of expression; it provides a
      proof-of-concept for future experiments exploring tissue-specific gene expression
      within lichens; and it highlights the utility of LMD for use in lichen systems.

PMID- 30296709
TI  - Single bout of low-intensity exercise produces modestly favorable changes in
      glycemic and lipidemic profiles after ingestion of non-isoglucidic breakfasts.
AB  - OBJECTIVES: The aim of this study was to investigate the acute effects of low
      intensity exercise on the postprandial hormonal and metabolic milieu induced by
      breakfast consumption. METHODS: Exercise began 100min after the initiation of
      breakfast consumption and consisted of cycling at 40% of maximum oxygen uptake
      for 20min. Three different breakfasts were used to elicit the postprandial state:
      B1 = skimmed milk (125 mL) and 30g corn flakes; B2 = skimmed milk (220 mL), 200g
      apple, 30g cocoa cream-filled sponge cake; B3 = skimmed milk (125 mL), 50g bread,
      150g apple, and 15g hazelnut and cocoa spread. Nineteen young healthy
      participants (8M/11 F; body mass index 22.7 +/- 0.5 kg/m2; age 31 +/- 0.7 y)
      consumed the three breakfasts, as well as an oral glucose load (50-g oral glucose
      tolerance test), under either resting or exercise conditions, in a randomized
      crossover fashion. Blood glucose, insulinemia, ghrelinemia, lipidemia, and
      satiety were measured throughout the studies. To evaluate the metabolic effects
      of exercise, the changes that glucose, insulin, ghrelin, free fatty acid
      exhibited in the interval 90 to 120min were analyzed with a two-way repeated
      measures analysis of variance (factor 1: type of oral test; factor 2:
      resting/exercise condition). RESULTS: No interaction between the two factors was
      found for any of the examined variables. Light exercise produced a modest,
      significant decrease in blood glucose levels (P = 0.004) and a modest,
      significant increase in free fatty acid levels (P = 0.002) with respect to the
      resting condition. CONCLUSIONS: These findings suggest that short, mild exercise
      has beneficial effects on postprandial metabolism and this may have direct
      bearing on the issue of counteracting the epidemic rising of sedentary lifestyle
      of the general population.

PMID- 30296708
TI  - Hydroxylated furanoditerpenoids from pupal cases produced by the bruchid beetle
      Sulcobruchus sauteri inside the seeds of Caesalpinia decapetala.
AB  - Seven undescribed hydroxylated cassane-type furanoditerpenoids were isolated from
      pupal cases formed from the secretion/excretion of the larvae of the wild bruchid
      seed beetle Sulcobruchus sauteri in infested Caesalpinia decapetala seeds, and
      their structures were elucidated by interpreting their spectra. The hydroxylated
      furanoditerpenoids found in the pupal cases were not present in the seeds of the
      host plant. Caesalacetal and caesaljapin obtained from the intact seeds exhibited
      larvicidal activity against the larvae of Aedes albopictus, while the
      hydroxylated furanoditerpenoids isolated from the pupal cases were inactive. The
      larvae of S. sauteri are proposed to detoxify larvicidal diterpenoids that occur
      in the seeds of the host plant by regiospecific hydroxylation.

PMID- 30296710
TI  - Corrigendum to "Effect of dexmedetomidine on intraocular pressure in patients
      undergoing robot-assisted laparoscopic radical prostatectomy under total
      intravenous anesthesia: A randomized, double blinded placebo controlled clinical
      trial" J. Clin. Anesth. 49 (2018) 30-35.

PMID- 30296711
TI  - Genomic selection for meat quality traits in Nelore cattle.
AB  - The objective of this study was to present heritability estimates and accuracy of
      genomic prediction using different methods for meat quality traits in Nelore
      cattle. Approximately 5000 animals with phenotypes and genotypes of 412,000 SNPs,
      were divided into two groups: (1) training population: animals born from 2008 to
      2013 and (2) validation population: animals born in 2014. A single-trait animal
      model was used to estimate heritability and to adjust the phenotype. The methods
      of GBLUP, Improved Bayesian Lasso and Bayes Cpi were performed to estimate the
      SNP effects. Accuracy of genomic prediction was calculated using Pearson's
      correlations between direct genomic values and adjusted phenotypes, divided by
      the square root of heritability of each trait (0.03-0.19). The accuracies varied
      from 0.23 to 0.73, with the lowest accuracies estimated for traits associated
      with fat content and the greatest accuracies observed for traits of meat color
      and tenderness. There were small differences in genomic prediction accuracy
      between methods.

PMID- 30296712
TI  - Quantitative analysis of serum chemokines associated with treatment failure of
      direct-acting antivirals in chronic hepatitis C.
AB  - Although serum chemokine levels have been reported to influence the outcome of
      interferon-based treatment in patients with chronic hepatitis C, their effect on
      the hepatitis C virus (HCV) response to direct-acting antiviral agents (DAAs),
      which can achieve high rates of a sustained virological response (SVR), is
      largely unknown. To clarify this relationship, 9 chemokines (eotaxin, GRO-alpha,
      IL-8, IP-10, MCP-1, MIP-1alpha, MIP-1beta, RANTES, and SDF-1alpha) were
      quantified before, during, and after DAA treatment using serum samples obtained
      from 57 patients with chronic hepatitis C. All baseline median chemokine levels
      were significantly higher in patients with chronic hepatitis C than in healthy
      subjects (P < 0.05). In particular, lower MIP-1beta (<=71.5 pg/mL) and higher
      RANTES (>671.5 pg/mL) levels were significantly associated with patients who
      failed to clear HCV RNA (P = 0.0039 and 0.013, respectively). Prediction of a
      clinical response based on a combination of these chemokines demonstrated high
      sensitivity (82%), specificity (85%), negative predictive value (95%), and area
      under the curve (0.833). The non-SVR rate (56.3%; 9 of 16) was significantly
      higher in patients with low MIP-1beta and high RANTES compared with other
      combinations. Moreover, baseline MIP-1beta and RANTES were both additive and
      independent for predicting a non-SVR. Apart from an increase in eotaxin, all
      chemokines became decreased in patients with a SVR. In conclusion, a combination
      of serum MIP-1beta and RANTES levels may be predictive of a treatment response to
      DAAs in Japanese patients with chronic hepatitis C.

PMID- 30296713
TI  - Influence of proinflammatory cytokine gene polymorphisms on the risk of COPD and
      the levels of plasma protein.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a complex and
      multifactorial disease involving systemic inflammation. Although certain genetic
      components have been implicated in the development and progression of this
      disease, few studies have examined the participation of polymorphisms in
      proinflammatory genes and the extent to which polymorphisms are related to plasma
      levels of cytokines involved in the inflammatory process. METHODS: Of the 1125
      smokers participating in the study, 438 had COPD, and 687 did not. We determined
      the genotype of 5 SNPs distributed in the genes: IL6, CXL8, CSF2, CCL1 and IL1B.
      The plasma protein expression of these genes was also evaluated and categorized
      according to genotype and the severity of COPD (GOLD grade). RESULTS: An analysis
      using the codominant model showed an association between rs1818879 in IL6 and
      susceptibility to COPD (GA OR = 1.1, AA OR = 1.77; p < 0.01), as well as an
      association between rs25882 in CSF2 and a greater severity of the disease (TC OR
      = 1.84, CC OR = 3.62; p < 0.01). No association was found between the presence of
      certain alleles in the SNPs and the plasma levels of the corresponding proteins.
      CONCLUSIONS: There are genetic polymorphisms related to susceptibility to COPD
      (rs1818879/A in IL6), as well as to the risk of greater severity of the disease
      (rs25882/T in CSF2). The presence of the alleles of interest did not
      significantly affect plasma levels of the codified proteins.

PMID- 30296714
TI  - Qualitative and quantitative analysis of Yifei Tongluo granules to identify main
      bioactive components using LC-DAD/MS and pharmacokinetic studies.
AB  - A standard fingerprint containing twelve common peaks was constructed from ten
      batches of Yifei Tongluo granules to evaluate batch-to-batch consistency by using
      HPLC-DAD. Additionally, the corresponding medicinal material attributes of these
      chemical constituents were analyzed according to the data acquired from the HPLC
      method and the identification was further carried out using the LC-MS/MS method.
      Comparing the retention time or accurate mass with previous studies or standards,
      the common components were tentatively identified in 50 min for ten batches of
      samples. At the same time, a reliable LC-MS/MS method was established to quantify
      marker substances simultaneously in 25 min, and the linear relationship of the
      standard curves was good in the experimental range. The validations of the method
      were successfully applied to the quality control and pharmacokinetic study. The
      results obtained from this study suggest that militarine was most abundant and
      the components in the granules caused pharmacokinetic herb-drug interactions in
      rats. This study provides a meaningful basis for evaluating the viability of
      Yifei Tongluo granules for clinical applications.

PMID- 30296715
TI  - Classification of Romanian medicinal plant extracts according to the therapeutic
      effects using thin layer chromatography and robust chemometrics.
AB  - Thin layer chromatography in combination with image analysis and advanced
      chemometric methods were successfully used to classify the medicinal herbs
      according to their therapeutic effects and usage. The investigations were
      conducted using two types of plates (HPTLC Silica gel 60 and HPTLC Silica gel 60
      F254) which were evaluated in UV light at 254 and 365 nm. The holistic evaluation
      of the numerical data corresponding different image processing channels (blue,
      grey, red, green) was performed by employing appropriate multivariate methods:
      hierarchical cluster analysis (HCA), principal component analysis (PCA), fuzzy
      principal component analysis (FPCA) and linear discriminant analysis (LDA)
      applied to the first relevant principal components. The results obtained by
      applying LDA method indicate a highly accurate separation of the medicinal herbs
      within the four groups, in good agreement with therapeutic effects and usage.
      According to this classification, the best image processing channels were
      identified for each of the investigated HPTLC plates: blue channel for HPTLC
      Silica gel 60 F254 (with 92.9% percent of discrimination in case of PCA and FPCA)
      and respectively red channel for HPTLC Silica gel 60 (with 93.9% percent of
      discrimination in case of FPCA). The 2D and 3D score scatterplots illustrate also
      the accurate and reliable discrimination between the four distinct groups.

PMID- 30296716
TI  - Assessment of the higher order structure of Humira(r), Remicade(r), Avastin(r),
      Rituxan(r), Herceptin(r), and Enbrel(r) by 2D-NMR fingerprinting.
AB  - The advent of monoclonal antibody biosimilar products has stimulated the
      development of analytical methods that can better characterize an important
      quality attribute, namely the higher order structure (HOS). Here, we propose a
      simple approach based on heteronuclear 2D NMR techniques at natural abundance for
      generating spectral fingerprints of the HOS at high resolution. We show that the
      proposed method can assess the HOS of six therapeutic products, adalimumab
      (Humira(r)), bevacizumab (Avastin(r)), infliximab (Remicade(r)), rituximab
      (Rituxan(r)), trastuzumab (Herceptin(r)), and Etanercept (Enbrel(r)). After
      treatment with immobilized papain, the purified fragments (Fab and Fc) were
      analyzed by 2D proton-nitrogen and proton-carbon NMR correlations. All Fab and Fc
      fragments produced high-resolution 2D-NMR spectra from which assessment of their
      higher order structure can be performed in the context of comparability studies.
      In particular, the two different sequences of Fc fragments could be unambiguously
      distinguished. The results show that it is possible to obtain structurally
      dependent information at amino acid resolution of these important therapeutic
      agents.

PMID- 30296717
TI  - Venous thrombosis and breast cancer in older women: Racial differences in risk
      factors and mortality.
AB  - BACKGROUND: Risk factors for venous thromboembolism (VTE) in women with breast
      cancer are not known by race. OBJECTIVES: The purpose of our study was to
      determine risk factors for VTE and VTE associated mortality in white and black
      women with breast cancer. PATIENTS AND METHODS: The SEER-Medicare merged database
      (2000 to 2011) was used for women 65 years and older diagnosed with breast
      cancer. Stratified by race, logistic regression was used to examine risk factors
      for VTE and Cox proportional hazards regression was used to evaluate the effect
      of VTE on mortality. RESULTS: There were 276,028 women 65 years and older with
      breast cancer. Of those, 6.4% white and 10.1% black women with breast cancer had
      a diagnosis of VTE. In adjusted analyses by race, risk of VTE increased with each
      year of age in both white and black cohorts. VTE was independently associated
      with distant metastasis and coexisting medical conditions in white women and in
      black women, hypertension, heart failure and hyperlipidemia were determinants of
      VTE. VTE was not associated with distant metastasis in black women. Tumor size,
      grade, and receptor status were also not independently associated with VTE risk
      in either white or black women. VTE accorded a higher risk of death in both white
      (HR = 1.49, 95% CI, 1.34-1.65) and black women (HR = 1.57, 95% CI, 1.23-2.00)
      with breast cancer. CONCLUSION: The study identified VTE risk factors and effect
      of VTE on mortality in white and black older women with breast cancer.

PMID- 30296718
TI  - Highly selective and sensitive LC-MS/MS quantification of a therapeutic protein
      in human serum using immunoaffinity capture enrichment.
AB  - We report the development, validation and application of a liquid chromatography
      tandem mass spectrometry (LC-MS/MS) bioanalytical method for the determination of
      a recombinant protein drug candidate, NVS001, in human serum. A unique surrogate
      peptide, IPAETTIYNR (IPA), was identified to distinguish NVS001 from its
      endogenous counterpart, i.e., the full length and the C-terminal of protein X in
      LC-MS/MS. The selection of IPA for the LC-MS/MS determination of NVS001 was
      supported by the absence of peak responses due to endogenous components in the LC
      MS/MS chromatograms of the extracted blank human serum samples. The optimal
      chromatographic separation of IPA from the extracted matrix components was
      achieved on a Waters Cortecs C18 (100 * 2.1 mm, 2.7 MUm) column using gradient
      elution with a run cycle time of approximately 7.5 min. The mobile phases were
      water containing 0.1% formic acid (mobile phase A) and acetonitrile containing
      0.1% formic acid (mobile phase B). The method was validated for specificity,
      sensitivity, matrix effect, recovery, linearity, accuracy and precision, dilution
      integrity, and stability. The validated assay dynamic range was 10.0 to 1000
      ng/mL using a 50 MUL sample volume. The accuracy and precision for the LLOQ (10.0
      ng/mL) sample results were within +/-9.2% bias and <=6.0% CV, respectively. From
      the intra-day and inter-day assay performance evaluations, the precision of the
      QC sample (30, 500 and 750 ng/mL) results were <=3.5% CV and the accuracy within
      +/-3.3% bias, respectively. An additional assessment of incurred sample
      reanalysis (ISR) was conducted to demonstrate the ruggedness and robustness of
      the assay method. The validated method was successfully implemented in support of
      a first-in-human study.

PMID- 30296719
TI  - Analyzing terephthalate metabolites in human urine as biomarkers of exposure:
      Importance of selection of metabolites and deconjugation enzyme.

PMID- 30296720
TI  - A rapid analysis of piroxicam in beagle plasma applying evaporation-free liquid
      liquid extraction by supercritical fluid chromatography-tandem mass spectrometry.
AB  - Bioequivalence study is highly prized to piroxicam (PIRO), since its generic
      products have been widely used worldwide. The present work was undertaken to
      explore the pharmacokinetic behaviors and bioequivalence of two branded PIRO
      tablets in beagle dogs using the supercritical fluid chromatography tandem mass
      spectrometry (SFC-MS/MS) method. Here, a fast evaporation-free liquid-liquid
      extraction (EF-LLE) method using ethyl acetate was developed for extracting PIRO
      from beagle dog plasma. To improve the response as well as peaks elution and
      symmetry of analytes, several key factors were investigated including post-column
      compensation, stationary phase, mobile phase, column temperature, back pressure
      and flow rate, and finally the analytes were eluted on an ACQUITY UPC2TM BEH 2-EP
      column (100 * 3 mm, 1.7 MUm) within only 2.5 min in optimal conditions. The
      performance of the established method was evaluated, good linearity was found
      over the concentration range of 5-5000 ng/mL (R2 >= 0.994) with a lower limit of
      quantification (LLOQ) of 5 ng/mL. Accuracy of all quality control (QC) samples
      were between 96.6% and 99.6% with a satisfactory intra and inter-day precision
      (RSD values < 6.6%). The proposed rapid, sensitive, user-friendly and high
      throughput method will be an alternative way for PIRO analysis in biological
      samples.

PMID- 30296721
TI  - Reducing inequality summer by summer: Lessons from an evaluation of the Boston
      Summer Youth Employment Program.
AB  - Many U.S. cities have implemented Summer Youth Employment Programs (SYEPs) with
      the hope of improving long-term behavioral, academic, and economic outcomes among
      program participants, particularly inner-city, low-income, and non-white youth.
      While recent empirical studies show positive impacts for some outcomes, little is
      known about program mechanisms and the potential to reduce inequality across
      groups. Using an embedded randomized control trial, this study evaluates
      improvements in short-term outcomes for the Boston SYEP based on survey data
      collected for both treatment and control groups during the summers of 2015, 2016,
      and 2017. Participants reported increases in community engagement and social
      skills, job readiness skills, and college aspirations that were significantly
      different from the control group. In most cases, the largest gains were observed
      for non-white youth suggesting that the program may have the capacity to reduce
      inequality across groups. Our hope is that this article will serve as a resource
      for those seeking to understand how summer jobs programs work and for whom, and
      to use these findings to strengthen and target the SYEP intervention. We also
      provide practical lessons learned regarding the development and deployment of our
      survey instrument to both the treatment and control groups among the youth
      population.

PMID- 30296722
TI  - Assessing the performance of the least developed countries in terms of the
      Millennium Development Goals.
AB  - This article presents a proposal for assessing the progress of least developed
      countries towards the achievement of the Millennium Development Goals over the
      period 2000-2015. Composite indices are built to perform spatial and temporal
      benchmarking relying on the P2 Distance method. The results are contrasted with
      other indices developed under a multi-criterion approach with a double reference
      point. The main findings are that all the countries have improved their situation
      and country disparities have been reduced. Cambodia and Ethiopia have registered
      the best trends and South Sudan and Timor-Leste show the worse performance.
      Considering the position in the 2015 ranking, Rwanda and Bhutan performed the
      best, while Somalia and Chad rank in the last position. Having now reached the
      end of the Millennium Development Goals period, the gap with respect to the world
      average indicates that much work remains to be done in the 2030 Agenda for
      Sustainable Development.

PMID- 30296723
TI  - Associations between upper extremity injury patterns in side impact motor vehicle
      collisions with occupant and crash characteristics.
AB  - INTRODUCTION: Side impact motor vehicle collisions (MVC) represent a significant
      burden of mortality and morbidity caused by automotive injury within the United
      States. The objective of this study was to evaluate the relationship between
      upper extremity (UE) injury patterns and contact sources in side impact MVC with
      occupant and crash variables. METHODS: Crash Injury Research and Engineering
      Network data obtained from 1998 to 2012 were used to evaluate UE injuries in side
      impact crashes. First row drivers and passengers that were at least 16 years old
      with complete crash information were included. Side impact crashes were defined
      to have an area of deformation to the side of the vehicle and a principal
      direction of force between 60 degrees  and 120 degrees  or 240 degrees  and 300
      degrees . Injuries were stratified by type, anatomic location, and Abbreviated
      Injury Scale (AIS) severity. Occupant variables included age, sex, height,
      weight, body mass index, and Injury Severity Score. Vehicle and crash variables
      included in the analysis were change in vehicle velocity at the time of impact,
      maximum door intrusion, maximum B-pillar intrusion, seat track position, belt
      use, vehicle type, impact type, and injury source. Statistical analysis of the UE
      injury data included descriptive statistics, linear regression analyses with
      occupant variables, and logistic regression analyses with vehicle and crash
      variables. RESULTS: There were 903 UE injuries among 408 case occupants. The most
      common injury type was soft tissue injury (72.5%). The majority of fractures were
      proximal to and including the humerus (70.3%) with the clavicle being the most
      common fracture location (N = 89). AIS 2+ UE injuries were associated with a
      significantly higher mean occupant Injury Severity Score than AIS 1 UE injuries
      (p = 0.01). Contact with the door was the leading cause of UE injury (34.2%). The
      odds (OR [95% confidence interval], p-value) of an AIS 2+ UE injury due to
      contact with the B-pillar (5.3 [3.1, 9.1], <0.0001), door (1.9 [1.3, 2.7],
      0.0006), and steering wheel/assembly (2.7 [1.1, 6.3], 0.03) were significantly
      higher than all other injury sources combined. Scapula fractures were
      significantly associated with rearward seat track positions (1.46 [1.04, 2.05],
      0.03). CONCLUSIONS: This study provides insight into UE injury patterns in side
      impact MVC. The clavicle was the most common UE fracture location. Contact with
      the door resulted in the highest number of UE injuries and the B-pillar resulted
      in the most severe injuries. Additionally, exposure to greater B-pillar intrusion
      was associated with increased odds of scapula and clavicle fractures in side
      impacts.

PMID- 30296724
TI  - Sex-specific trajectories of measures of cardiovascular health during childhood
      and adolescence: A prospective cohort study.
AB  - BACKGROUND AND AIMS: Sex differences in measures of cardiovascular health in
      adults are well documented. However, the sex-specific aetiology of cardiovascular
      health across childhood and adolescence is poorly understood. METHODS: We
      examined sex differences in trajectories of 11 measures of cardiovascular health
      from birth to 18 years, in a contemporary birth cohort study in England (N
      participants per outcomes: 662-13,985, N repeated measures per outcome: 1,831
      112,768). Outcomes were measured over varying time spans from birth or mid
      childhood to age 18 and with different numbers of repeated measures per outcome.
      Analyses were performed using fractional polynomial and linear spline multilevel
      models. RESULTS: Females had higher mean BMI, height-adjusted fat mass, pulse
      rate, insulin, triglycerides, and non-high-density lipoprotein cholesterol (HDL
      c) and lower mean height-adjusted lean mass from birth or from mid-childhood to
      age 18. For example, mean non-HDL-c was 0.07 mmol/l (95% confidence interval
      (CI), 0.04, 0.10) higher in females compared with males at birth. By age 18, this
      difference persisted and widened to 0.19 mmol/l (95% CI, 0.16, 0.23) higher non
      HDL-c in females compared with males. Females had lower levels of glucose from
      mid-childhood and developed lower systolic blood pressure and higher HDL-c from
      mid-adolescence onward. For example, females had 0.08 mmol/l (95% CI, 0.05, 0.10)
      lower mean glucose compared with males at age seven which widened to a difference
      of 0.22 mmol/l (95% CI, 0.25, 0.19) at age 18. CONCLUSIONS: Sex differences in
      measures of cardiovascular health are apparent from birth or mid-childhood and
      change during early life. These differences may have implications for sex
      specific disease risk in future adult populations.

PMID- 30296725
TI  - The first competency based framework in genetics/genomics specifically for
      midwifery education and practice.
AB  - This paper details a competency framework to help address the need for structured
      guidance around genetic and genomic education and training for midwives. A one
      day expert panel consensus meeting was convened to review and revise a previously
      published joint framework for nurses, midwives and health visitors. Fifteen
      midwives from practice, management, education and policy and three genetic
      counsellors (two with midwifery backgrounds) attended. An in-depth knowledge of
      genetics/genomics was not a requirement. Personal narratives covering a range of
      experiences across the pre- and post-natal periods were used to stimulate
      discussion and debate. Identified themes were mapped to the original framework to
      identify gaps and differences. Inclusion of additional themes into the new
      framework was voted upon. All original competencies were found to be valid but
      required amendment in order to focus specifically on the role of the midwife and
      the needs of the mother, child and wider family. Revisions have resulted in a
      framework that is more directive and which addresses the time-critical nature of
      information-giving, decision-making, testing and referral that are crucial
      components of midwifery practice. Learning outcomes and practice indicators offer
      educators and trainers a means of developing student/staff knowledge and skills
      over time and with increasing experience.

PMID- 30296726
TI  - Evaluation of student perception of the Team-based Learning method (APA-TBL):
      Instrument construction and validation.
AB  - Team-based learning (TBL) is an educational strategy based on learning teams.
      Despite the advantages identified in the TBL literature, student perceptions must
      be better investigated using valid, reliable instruments. This study constructed
      and validated an instrument to evaluate student perceptions of the TBL method.
      Content and appearance assessment, construct validation and reliability analysis
      were performed. A total of 246 undergraduate nursing and medical students from a
      private institution in Sao Paulo, Brazil, participated in the study. After
      content validation, the instrument had 24 items distributed in five dimensions.
      Based on exploratory factor analysis, the instrument was appropriate, and the
      items were regrouped in four dimensions, with Cronbach's alpha values over 0.70.
      The Student Perception Evaluation of the TBL method (Avaliacao da Percepcao do
      Aluno-Team-Based Learning - APA-TBL) is an instrument with strong validity
      indicators. After validation, the revised instrument reflected that the student's
      perspective of method evaluation is not focused on TBL's formal execution but on
      the involved agents, their interaction and their influence on one another.

PMID- 30296727
TI  - Facilitating affective elements in learning - In a palliative care context.
AB  - The aim of this study was to explore ways clinical supervisors facilitate the
      learning of the affective elements of professional competence in a clinical
      palliative care environment. The secondary aim was to advocate for and raise
      awareness of the importance of the affective domain in medical education. A
      clinical palliative care learning environment has been reported to be emotionally
      challenging. The affective and transformative learning processes taking place
      requires special support. However, little is known about how clinical supervisors
      facilitate this learning processes. A qualitative, explorative study was designed
      to capture supervisors' perceptions of their supervision using semi-structured
      interviews. Six experienced clinical supervisors working within a palliative care
      context were recruited using convenience sampling. Data were analyzed using
      inductive content analysis. The affective elements were viewed as essential for
      learning, clinical supervision, and professional competency. Supervisors use a
      variety of different ways of facilitation. Four main themes were identified;
      building a relationship, creating space for learning, creating a pedagogical
      environment, and Mirroring.

PMID- 30296728
TI  - Space quantization between the object and image spaces of a microscopic
      stereovision system with a stereo light microscope.
AB  - Microscopic stereovision systems with a stereo light microscope have been used
      for quantized observations and measurements in microscopy fields. These
      applications depend on a quantization mathematical relationship between the
      object space and the image space. In this article, a novel, practical space
      quantization method was proposed. It was derived from two defined base cell
      matrices. First, it captured a series of stereo images of markers moving in
      various directions through the object space. The world and image coordinates of
      markers were acquired, stored and used to create the two base cell matrices.
      Next, a space quantization relationship between the object space and the image
      space was derived from analysis of the two base cell matrices. Finally, if two
      matching points located in the image space were given, the world coordinates of
      their object point could be calculated by the above space quantization
      relationship. The results show that this method of quantizing the two spaces
      could achieve a positioning precision of approximately +/-5 MUm in the horizontal
      direction and approximately +/-10 MUm in the vertical direction. It has a very
      simple expression, but it is more practical and efficient than other traditional
      projection methods. In addition, it has a better performance and can be widely
      used in several microscopy fields, such as microscopic shape reconstruction,
      micromanipulation, microassembly, and microinjection.

PMID- 30296729
TI  - Associations of stress, self-esteem, and collective efficacy with flow in
      simulation among nursing students: A descriptive cross-sectional study.
AB  - BACKGROUND: Simulation-based learning was developed to enable nursing and medical
      students to obtain clinical experience in a safe and controlled environment. The
      extent to which students concentrate in simulation situations can influence their
      educational outcomes. However, there are no studies yet on the factors that
      influence flow in simulation practice. Understanding which factors influence flow
      might help in achieving better simulation-based learning outcomes. OBJECTIVES:
      The purpose of this study was to identify the factors related to flow in
      simulation practice, including stress, self-esteem, and collective efficacy.
      DESIGN: This was a descriptive cross-sectional study. SETTING: A university in
      South Korea during the 2015 academic year. PARTICIPANTS: This study was conducted
      with 84 senior nursing students. Their average age was 23 years old and >90% were
      female. METHODS: The stress, self-esteem, and collective efficacy of senior
      nursing students were measured before simulation practice, while flow in
      simulation practice was measured after simulation. RESULTS: Flow during
      simulation practice was positively correlated with self-esteem and collective
      efficacy, but negatively correlated with stress. Furthermore, only collective
      efficacy was a significant predictor of flow during simulation. CONCLUSIONS:
      Nursing education must be oriented to help emphasize collective efficacy to
      improve students' outcomes from simulation-based learning.

PMID- 30296730
TI  - Using high fidelity simulation to increase nursing students' clinical postpartum
      and newborn assessment proficiency: A mixed-methods research study.
AB  - OBJECTIVE: The objective of this study was to explore the benefits of using High
      Fidelity Simulators (HFS) to teach maternal postpartum and newborn assessment
      skills to student nurses before they interacted with actual hospital patients.
      DESIGN: This descriptive, observational study employed a mixed-method design
      using a Qualtrics online survey instrument. SETTING: The study was set at a
      Midwestern university. PARTICIPANTS: The study used a convenience sample of third
      year BSN nursing students (n = 132). METHODS: After participating in an HFS
      experience and completing a maternity clinical rotation, students took an online
      Qualtrics survey evaluating the benefits and drawbacks of the HFS experience.
      RESULTS: Students valued the HFS experience at an average score of 3.82 on a
      Likert Scale of 1-5. Open-ended questions identified three themes: psychomotor
      learning leading to skill acquisition, affective learning, and simulation
      restructuring to provide more time, better instructor preparation, and smaller
      groups. CONCLUSION: This study's data supports the use of HFS to enhance nursing
      care and education, with special attention given to instructional consistency.
      Practicing new assessment skills in a non-threatening, safe environment gives
      students expertise and confidence while promoting the development of critical
      thinking skills.

PMID- 30296731
TI  - Assessing the educational impact of the dementia champions programme in Scotland:
      Implications for evaluating professional dementia education.
AB  - Increasing numbers of people with dementia are living longer with a higher
      likelihood of requiring hospital care for physical conditions including falls,
      infections and stroke (Boaden, 2016). However, the literature is replete with
      descriptions of poor care and hospital care experiences that have fallen well
      below the expectations of people with dementia, their families and friends.
      Although poor care is unacceptable, it is unsurprising given that dementia
      education for health and social care professionals is often inadequate and
      inconsistent. This results in most healthcare staff being ill-equipped and
      lacking the confidence to work with people living with dementia. The first of
      Scotland's National Dementia Strategies committed to "improve the response to
      dementia in general hospital settings including alternatives to admission and
      better planning for discharge" (Scottish Government, 2010). The educational
      response was the commissioning of the Dementia Champions programme. Since 2011,
      the programme has developed over 800 health and social care professionals working
      in general hospital and related settings to be change agents in dementia care.
      This article will outline the theoretical underpinning of the programme and
      present pooled results from four cohorts (2014-2017) (n = 524). A repeated
      measure design (pre and post programme) was used to measure attitudes towards
      people with dementia; self-efficacy and knowledge of dementia. The findings
      suggest that the education had a statistically significant positive effect on all
      intended outcomes, indicating the potential for practice change. We discuss these
      findings in relation to the literature, and respond to the calls for high quality
      evaluation to measure the effectiveness of dementia education, the challenges and
      potential directions for measuring educational effectiveness and capturing
      transfer of learning.

PMID- 30296732
TI  - Use of eHealth and mHealth technology by persons with multiple sclerosis.
AB  - BACKGROUND: Health communication has evolved substantially over the last few
      years as the field of electronic health (eHealth) technologies has emerged. It is
      unknown what demographic and clinical characteristics are associated with use of
      eHealth technologies in MS. As these technologies are more widely adopted in
      health settings, it is important that health care providers understand who is
      using them, and to recognize potential disparities if they exist. OBJECTIVE: We
      aimed to examine the use of eHealth technologies among persons with multiple
      sclerosis (MS), including the adoption of mobile Health (mHealth) applications
      (apps) and telehealth, perceived benefits of using mHealth apps, and
      sociodemographic and clinical characteristics associated with use of these
      technologies. METHODS: In the spring 2017, we surveyed participants in the North
      American Research Committee on Multiple Sclerosis (NARCOMS) Registry about their
      use of eHealth technologies using questions adapted from the Health Information
      National Trends (HINTS) 4 Cycle 4 survey. Participants reported their internet
      use, electronic devices used, use of health related software apps and perceived
      benefits from using those apps, and their interest in exchanging medical
      information with a health care professional electronically. We used descriptive
      statistics to report use of eHealth technologies and multivariable logistic
      regression to evaluate factors associated with use of electronic devices, use of
      mHealth apps, telehealth use, and perceived benefits of using mHealth apps.
      RESULTS: Of 6423 participants included in the analysis most participants were
      female, and white, with a mean (SD) age of 59.7 (10.1) years. Overall, 5408
      (84.2%) had exchanged medical information with a health professional most often
      using a secure online portal (1839, 28.6%), followed by email (1327, 20.7%). of
      the 5529 smartphone and tablet users, 2556 (46.2%) used a mHealth app. Factors
      associated with a higher likelihood of reporting use of smartphones or tablets,
      mHealth apps and with perceived benefits of using these apps included online
      survey response, younger age, having comorbidities, and higher income and
      education levels. CONCLUSION: Use of eHealth technologies is common in the MS
      population and facilitates the exchange of health care information with
      providers. Use of mHealth apps is perceived to have health benefits. However, use
      of eHealth and mHealth technologies varies substantially with sociodemographic
      factors, and health care providers need to be aware of these disparities as these
      technologies are increasingly leveraged in health care settings.

PMID- 30296733
TI  - In vivo combined treatment of rats with ivermectin and aged garlic extract
      attenuates ivermectin-induced cytogenotoxicity in bone marrow cells.
AB  - Ivermectin (IVM) is widely used in human and veterinary medicine for the control
      of parasitic infections. Researches revealed new avenues of medicinal
      applications of IVM as an antiviral and an anticancer agent. Very little is known
      about the genotoxic potential of IVM and the available literature is
      contradictory. The objective of this study was to evaluate the possible genetic
      damage caused by IVM. Male Sprague Dawley rats were intraperitoneally given IVM
      at doses between 0.2 mg and 3.2 mg/kg body weight (b. w). Percentages of mitotic
      and aberrant bone marrow cells were followed. The results indicated that IVM by
      itself, at doses higher than the recommended dose, induced significant levels of
      cytogenetic toxicity. To this end, we decided to investigate the potential use of
      combination of varying doses of aged garlic extract (AGE); 300, 600 and 1200
      mg/kg b w and the minimum detectable toxic (MDT) dose of IVM; 0.4 mg/kg. A
      powerful capacity of AGE to reduce IVM cytogenetic effects was demonstrated.
      Overall, the data prove the safety of IVM at the recommended dose and provide a
      strong scientific evidence for superior protection of AGE against possible
      cytogenotoxic side effects of IVM, confirming the existence of a meaningful
      therapeutic window.

PMID- 30296734
TI  - Making a 'JUMP' from paediatric to adult healthcare: A transitional program for
      young adults with chronic neurological disease.
AB  - BACKGROUND: "JUMP" is a multidisciplinary program based at the Pitie-Salpetriere
      Hospital Paris that transitions young adults with chronic neurological conditions
      from paediatric to adult healthcare. Transitional care programs have been shown
      to improve medical, educational and psychosocial outcomes for adolescent
      patients. METHODS: Demographic details and health-related variables of all
      patients referred to the JUMP program were collected. Satisfaction outcome
      measures were the 18-item On Your Own Feet Transfer Experience Scale (OYOF-TES)
      and a visual analogue scale, which assessed overall satisfaction with the
      transfer process. Scales were sent to JUMP patients attending the JUMP day
      hospital (n = 94) and their parents (n = 94). RESULTS: Since its inception, 111
      patients have been seen in the JUMP program. Nine neurological clinical syndromes
      and four main underlying etiologies were identified. Approximately half of all
      questionnaires and scales (86/188) sent to patients and parents were returned.
      Eighty-nine percent of patients and 91% of parents were very satisfied with their
      transfer experience. There was a strong, positive correlation between patient and
      parent satisfaction [r = 0.910; p < 0.0001]. CONCLUSION: The JUMP program which
      is rooted in a multidisciplinary and coordinated approach to transitional care
      encompasses a broad range of neuro-pathologies. Overall, satisfaction levels were
      high amongst patients within the program, and their parents. The key role played
      by the coordination nurse specialists throughout the transfer process is a likely
      key determinant in satisfaction levels.

PMID- 30296736
TI  - Comparative efficacy and safety of tyrosine kinase inhibitors for chronic myeloid
      leukaemia: A systematic review and network meta-analysis.
AB  - BACKGROUND: The pharmacotherapy of chronic myeloid leukaemia (CML) is mainly
      based on tyrosine kinase inhibitors (TKIs). The aim of this study was to compare
      the efficacy and safety of all TKIs in CML patients. METHODS: We conducted a
      systematic review with network meta-analysis (NMA) of randomised controlled
      trials (RCTs), including imatinib, nilotinib, dasatinib, bosutinib, radotinib and
      ponatinib. Searches were performed in PubMed, Scopus, Web of Science and SciELo
      (March 2018). The NMAs were built for six outcomes at 12 months: complete
      cytogenetic response (CCyR), major cytogenetic response (MCyR), deep molecular
      response, major molecular response (MMR), complete haematologic response and
      incidence of serious adverse events. We conducted rank order and surface under
      the cumulative ranking curve (SUCRA) analyses. RESULTS: Thirteen RCTs were
      included (n = 5079 patients). Statistical differences were observed for some
      comparisons in all outcomes. Imatinib 400 mg was considered the safest drug
      (SUCRA values of 10.3%) but presented low efficacy. Overall, nilotinib 600 mg was
      superior to the other TKI in efficacy (SUCRA values of 61.1% for CCyR, 81.0% for
      MMR, 90.0% for MCyR); however, no data on its safety profile at 12 months were
      reported. INTERPRETATION: Our results suggest that nilotinib should be upgraded
      to first-line therapy for CML, although further cost-effectiveness analyses,
      including the new TKI (i.e., ponatinib, radotinib), are needed.

PMID- 30296735
TI  - Pain intensity as a moderator of the association between opioid use and insomnia
      symptoms among adults with chronic pain.
AB  - OBJECTIVE: Research documenting the impact of opioid use on sleep among
      individuals with chronic pain has been mixed. This study aimed to determine if
      pain intensity moderates the association between opioid use and insomnia symptoms
      among adults with comorbid symptoms of insomnia and chronic widespread pain.
      METHODS: Participants (N = 144; 95% female; mean age = 51.6, SD = 11.4) completed
      assessments of insomnia symptoms, pain and use of sleep/pain medication. Multiple
      regression was used to determine if pain intensity moderates the association
      between opioid use (yes/no) sleep onset latency (SOL), wake after sleep onset
      (WASO), sleep quality, or time in bed. Analyses controlled for gender, symptoms
      of sleep apnea, symptoms of depression, use of sleep medication (yes/no), and use
      of non-opioid pain medication (yes/no). RESULTS: Stronger pain intensity was
      associated with longer self-reported WASO and worse sleep quality, independent of
      opioid use. Conversely, opioid use was associated with longer time in bed,
      independent of pain intensity. Opioid use and pain intensity interacted in the
      prediction of SOL, such that opioid use (vs. non-use) was associated with longer
      SOL in the context of mild but not moderate to severe pain intensity.
      CONCLUSIONS: Opioid use was associated with more difficulty falling asleep among
      adults with chronic pain; however, this cross-sectional effect was only
      significant among those reporting lower pain intensity. Authors speculate that
      this effect is masked among those with severe pain because the pain-related sleep
      debt they acquire throughout the night then facilitates sleep onset the next day.

PMID- 30296737
TI  - Understanding mode of action can drive the translational pipeline towards more
      reliable health benefits for probiotics.
AB  - The different levels of knowledge described in a translational pipeline (the
      connection of molecular mechanisms with pre-clinical physiological and human
      health effects) are not complete for many probiotics. At present, we are not in a
      position to fully understand the mechanistic basis of many well established
      probiotic health benefits which, in turn, limits our ability to use mechanisms to
      predict which probiotics are likely to be effective in any given population. Here
      we suggest that this concept of a translation pipeline connecting mechanistic
      insights to probiotic efficacy can support the selection and production of
      improved probiotic products. Such a conceptual pipeline would also provide a
      framework for the design of clinical trials to convincingly demonstrate the
      benefit of probiotics to human health in well-defined subpopulations.

PMID- 30296738
TI  - An autopsy report of accidental burial in a beach sand hole.
AB  - We present a 23-year-old married couple who died by accidental burial in a beach
      sand hole. The victims fell into a hole that had been covered with a plastic
      sheet, and were buried suddenly by sand that had been piled on the top of the
      sheet. At autopsy, facial congestion; petechial hemorrhages in the conjunctivae
      and the oral mucosa; skin petechiae at the face, neck and upper chest; congestion
      and hemorrhages in the cervical lymph nodes; and some minor hemorrhages in the
      cervical muscles were found in both victims. Little sand was evident in the
      airway, while sand debris was found in the oral cavity. Prior reports suggest
      that aspiration of sand is a major contributing factor in asphyxia after
      accidental burials. However, neck and chest compression and face coverage by sand
      masses could induce lethal asphyxia without airway obstruction caused by sand
      aspiration. Asphyxia was deemed to be the cause of death in both individuals and
      was considered to result from chest compression by sand. In addition, compression
      of the neck may also have contributed to asphyxia. In this instance, the sand
      beach hole was excavated for recreational purposes. The potentially life
      threatening implications of beach sand hole excavations should be recognized and
      highlighted to prevent lethal accidents such as those described in this report.

PMID- 30296739
TI  - In vivo hepatocellular expression of interleukin-22 using penetratin-based hybrid
      nanoparticles as potential anti-hepatitis therapeutics.
AB  - Hepatocellular injury is the pathological hallmark of hepatitis and a crucial
      driver for the progression of liver diseases, while the treatment options are
      commonly restricted. Interleukin-22 (IL-22) has attracted special attention as a
      potent survival factor for hepatocytes that both prevents and repairs the injury
      of hepatocytes through activation of STAT3 signaling pathway. We hypothesized
      that the ability to generate potent expression of IL-22 locally for the treatment
      of severe hepatocellular injury in hepatitis was a promising strategy to enhance
      efficacy and overcome off-target effects. Accordingly, we developed a polypeptide
      penetratin-based hybrid nanoparticle system (PDPIA) carrying IL-22 gene by a self
      assembly process. This nanocomplex modified with penetratin featured direct
      translocation across the cellular or endosomal membrane but mild zeta-potential
      to facilitate the high cellular internalization and endosomal escape of the gene
      cargos as well as scarcely Kupffer cells uptake. More importantly, PDPIA afforded
      preferential liver accumulation and predominant hepatocytes internalization
      following systemic administration, which showed pharmacologically suitable organ
      and sub-organ-selective properties. Subsequent studies confirmed a considerable
      protective role of PDPIA in a model of severe hepatitis induced by concanavalin
      A, evidenced by reduced hepatocellular injury and evaded immune response. The
      locally expressed IL-22 by PDPIA activated STAT3/Erk signal transduction, and
      thus promoted hepatocyte regeneration, inhibited reactive oxygen species (ROS)
      accumulation as well as prevented the dysfunction of mitochondrial. In addition,
      this system did not manifest side effects or systemic toxicity in mice.
      Collectively, the high versatility of PDPIA rendered its promising applications
      might be an effective agent to treat various hepatic disorders.

PMID- 30296740
TI  - Long-term seizure outcome in pediatric patients with focal cortical dysplasia
      undergoing tailored and standard surgical resections.
AB  - PURPOSE: Focal cortical dysplasia (FCD) is the major cause of focal intractable
      epilepsy in childhood. Here we analyze the factors influencing the success of
      surgical treatment in a large cohort of children with histologically ascertained
      FCD. METHOD: A retrospective study of the effects of FCD type, surgical
      intervention, and age at surgery in a pediatric cohort. RESULTS: A total of 113
      patients (71 male; mean age at surgery 10.3 years; range 0-18) were analyzed; 45
      had undergone lesionectomy, 42 lobectomy, 18 multi-lobectomy, and eight
      hemispherotomy. Complete seizure control (Engel Ia) was achieved in 56% after two
      years, 52% at five years, and 50% at last follow-up (18-204 months). Resections
      were more extensive in younger patients (40% of the surgeries affecting more than
      one lobe in patients aged nine years or younger vs. 22% in patients older than
      nine years). While resections were more limited in older children, their long
      term outcome tended to be superior (42% seizure freedom in patients aged nine
      years or younger vs. 56% in patients older than nine years). The outcome in FCD I
      was not significantly inferior to that in FCD II. CONCLUSIONS: Our data confirm
      the long-term efficacy of surgery in children with FCD and epilepsy. An earlier
      age at surgery within this cohort did not predict a better long-term outcome, but
      it involved less-tailored surgical approaches. The data suggest that in patients
      with an unclear extent of the dysplastic area, later resections may offer
      advantages in terms of the precision of surgical-resection planning.

PMID- 30296741
TI  - A biological, fluorescence and computational examination of synthetic coumarin
      derivatives with antithrombotic potential.
AB  - BACKGROUND: Scientists still look for new drugs, which have anticoagulant
      properties. This is so important because existing anticoagulant drugs give many
      side effects, for example major bleeding. In this study we examined nine coumarin
      derivatives - candidates to be future antithrombotic drugs, which were
      synthetized and crystallized in our previous paper. METHODS: Here we show the
      fluorescence and fluorescence quenching of coumarin derivatives with di- or
      trimethoxybenzylamine moieties in C-3 position. All nine compounds were checked
      by lactate dehydrogenase assay to examine their cytotoxic activity on hepatic
      cells. We also investigated the other biological properties (bioactivity, drug
      likeness and blind docking) using computational tools. Lipophilicity coefficient
      logP of all obtained compounds was determined using by RP-TLC and compared to
      theoretical predictions. RESULTS: The obtained coumarins exhibited low lipophilic
      character. The substances bound with HSA and did not demonstrate cytotoxicity
      against isolated liver cells. The most interesting compound (3b) possessed two
      methoxy- group in 2- and 4-position in benzene ring, ability to interact with two
      HSA binding sites and probably smaller steric hindrance in comparison to other
      synthesized derivatives. CONCLUSIONS: Our present study shows that after
      examination of fluorescence, cytotoxic activity, lipophilicity, theoretical
      bioactivity, drug-likeness and blind docking of our synthesized compounds they
      have potential as antithrombotic medicines and may be candidates to be drugs
      after further studies.

PMID- 30296742
TI  - The association between inflammatory markers (iNOS, HO-1, IL-33, MIP-1beta) and
      depression with and without posttraumatic stress disorder.
AB  - BACKGROUND: Both major depression and posttraumatic stress disorder (PTSD) are
      characterized by inflammation, increased concentration levels of proinflammatory
      cytokines, decreased neurogenesis followed by neuroprogression, as well as
      mitochondrial and the hypothalamic-pituitary-adrenal axis dysfunction. Elevated
      levels of oxidative stress caused by an increased activity of prooxidants over
      antioxidants are also observed. Based on several reports, depressive episodes can
      lead to the sensitization of immune-inflammatory pathways. Thus, depression,
      PTSD, and depression comorbid with PTSD are associated with immune-inflammatory
      markers. The study aimed at evaluating concentration levels of iNOS, HO-1, IL-33,
      and MIP-1beta in depression with and without PTSD. METHODS: A total number of
      participants enrolled in the study was 460. Out of them, 420 subjects with
      various levels of depression severity constituted the study group (210 males and
      210 females), and 40 subjects (20 males and 20 females) constituted the control
      group. Each study group comprised 60 patients (30 males and 30 females) with mild
      depression (MD), moderate depression (MOD), severe depression (SeD), MD and PTSD
      (MD + PTSD), MOD and PTSD (MOD + PTSD), SeD and PTSD (SeD + PTSD), and with PTSD
      alone. At 7:00 a.m., all patients had serum concentrations of iNOS, HO-1, IL-33,
      MIP-1beta determined using ELISA. RESULTS: Both depression exacerbation and PTSD
      comorbidity led to elevated levels of iNOS, HO-1, IL-33, and MIP-1beta.
      CONCLUSION: Depression both with and without PTSD leads to elevated levels of
      inflammation and an oxidant/antioxidant imbalance. Alterations in both cytokines
      and oxidative stress are related to the mechanisms responsible for the
      development of depressive symptoms.

PMID- 30296743
TI  - Effects of Selol 5% supplementation on tissue antioxidant enzyme levels and
      peroxidation marker in healthy mice.
AB  - BACKGROUND: Selenium (Se) is an essential micronutrient for animals and humans
      used in the prevention or treatment of cancer. Selol is a mixture of
      selenitetriglycerides, containing Se(IV). It does not exhibit mutagenic activity
      and is less toxic than inorganic sodium selenite containing Se(IV). The
      antioxidant properties of the Selol were demonstrated using the blood of healthy
      animals. The aim of the study was to evaluate Selol as a Se supplement by
      determining the effect of its administration on the Se level and the antioxidant
      status in the tissues. METHODS: We examined the effect of long-term (28-day)
      Selol 5% supplementation on the activity of antioxidant enzymes, including the
      main selenoenzymes in healthy mice organs, such as liver, brain, lungs, and
      testis. Enzyme activities of the tissue homogenates and the concentration of
      malondialdehyde (MDA) as a biomarker of oxidative stress were measured using
      spectrophotometric methods. The selenium concentrations in the tissues were
      determined by inductively coupled plasma mass spectrometer (ICP-MS) as well.
      RESULTS: A significant increase in glutathione peroxidase, thioredoxin reductase,
      and glutathione S-transferase activity as well as the MDA concentration was
      observed in most of the studied tissues during the Selol 5% supplementation.
      CONCLUSIONS: Long-term supplementation with the new Se(IV) compound - Selol 5%
      significantly affects the activity of antioxidant enzymes and the redox state in
      healthy mice organs. In the healthy population Selol 5% seems to be a promising
      new antioxidant compound.

PMID- 30296745
TI  - A novel non-starch based cationic polymer as flocculant for harvesting
      microalgae.
AB  - This work intends towards the preparation of different grades of cationic locust
      bean gum biopolymer (CLBG) through the incorporation of 2,3
      epoxypropyltrimethylammonium chloride (GTMAC) on to the pristine locust bean gum
      (LBG) biopolymer. Among them the best grade was further selected, characterized
      and their flocculation efficacy was evaluated towards harvesting of three
      different indigenous isolated green microalgae viz. Chlorella sp. NCQ,
      Micractinium sp. NCS2 and Scenedesmus sp. CBIIT(ISM). Flocculation efficiency of
      96.68%, 96.64%, and 97.42% were obtained for Chlorella sp. NCQ, Micractinium sp.
      NCS2 and Scenedesmus sp. CBIIT(ISM) at an optimum dosage of 55, 40, and 30 ppm
      respectively. Thus CLBG was proven to be an efficient flocculant towards
      harvesting of green microalgae than its natural form.

PMID- 30296744
TI  - Virome definition in cerebrospinal fluid of patients with neurological
      complications after hematopoietic stem cell transplantation.
AB  - BACKGROUND: Neurological complications (NC) in allogeneic hematopoietic stem cell
      transplant (HSCT) recipients lead to long-term sequelae and result in significant
      morbidity and mortality. Since risk factors for NC include viral infection or
      reactivation, virome inspection after HSCT might be helpful to the clinical
      management of patients after HSCT. OBJECTIVES AND STUDY DESIGN: In this study we
      investigated whether any viruses are found in association with NC after HSCT. For
      this purpose, unbiased next generation sequencing (NGS) was used to characterize
      nucleic acid (NA) content in cerebrospinal fluid (CSF) taken at time of NC in 35
      HSCT patients. Virome definition in CSF from non-transplanted subjects (controls)
      was also tested to define the commensal flora. RESULTS AND CONCLUSIONS: A higher
      number of reads/contigs mapped to viruses in patients compared to the controls
      (7,626 vs 235). Besides bacteriophages, Torque teno virus (TTV) was also
      identified in both controls and patients. Interestingly, a significantly higher
      number of TTV-like sequences was detected in the patient samples (7,236 vs 9),
      showing similarities to distinct genotypes; 3/2,575, 2/1,692 and 2/2,969
      contigs/reads mapped to TTV11, TTV13 and Torque teno midi virus, respectively. In
      conclusion, unbiased NGS demonstrated to be a suitable approach to characterize
      the virome in samples containing limiting amounts of NA. The higher TTV levels
      and genetic diversity found in CSF of subjects with NC after HSCT might suggest a
      possible association between TTV reactivation and the disorder. However, further
      studies are needed to evaluate the possible role of TTV on NC in HSCT patients.

PMID- 30296746
TI  - Recovery of chlorophylls from spent biomass of Arthrospira platensis obtained
      after extraction of phycobiliproteins.
AB  - Extraction of chlorophylls has received scant attention or priority over
      phycobiliproteins from Arthrospira platensis. In fact extraction of chlorophylls
      from spent biomass (left after extraction of phycobiliproteins which goes as
      waste or underutilized) on drying, will improve the economics of the overall
      downstream processing. Ethanol (yield 5.75 mg/g, db), being a food grade solvent,
      was preferred over acetone and dimethyl sulfoxide in spite of their slightly
      better yields (5.85 mg/g, db). The best conditions were 100% concentration of
      ethanol, 1:8 S/L ratio, pH 6, 50  degrees C temperature and 1 h extraction time.
      An increase of 125% in yield besides reduction of 83.3% in extraction time (from
      6 to 1 h) could be achieved at standardized conditions. Low-Humidity drying was
      observed to be a possible alternative to freeze drying for drying of spent
      biomass. Ultrasonication as pre-treatment and ethanol as solvent were found
      effective for extraction of chlorophylls from dry spent biomass.

PMID- 30296747
TI  - Effect of nanosecond pulsed electric field treatment on cell proliferation of
      microalgae.
AB  - Photoautotrophic microalgae based biorefinery concepts are currently not
      competitive compared to other established production systems. Therefore,
      innovative upstream processes need to be developed to increase the
      competitiveness of photoautotrophic microalgae biorefinery concepts. Abiotic sub
      lethal stress induction via nanosecond pulsed electric field (nsPEF) treatment
      might be a viable process to increase the efficiency of photoautotrophic
      microalgae cultivation. In this work, an increased cell growth after nsPEF
      treatment was observable. Application of nsPEF to highly proliferating cells in a
      repetitive process resulted in a statistical significant increase in cell growth
      (p = 0.009). The effect was most pronounced after five days wherefore cellular
      structures and processes were analyzed to reveal a possible mechanism. Within
      this work, a protocol for increased cell proliferation with a possible mechanism
      was derived, which improves competitiveness of photoautotrophic microalgae
      biorefineries in the future. However, based on the derived mechanism, the results
      are also relevant for other microorganisms.

PMID- 30296748
TI  - Valorisation of digestate from biowaste through solid-state fermentation to
      obtain value added bioproducts: A first approach.
AB  - Digestate from biowaste was assessed as a potential source of bioproducts of
      commercial and industrial interest through solid-state fermentation. The targeted
      bioproducts were hydrolytic enzymes (cellulases and proteases from autochthonous
      microbiome), biosurfactants (sophorolipids produced from Starmella bombicola) and
      biopesticides (produced from Bacillus thuringiensis). Low cellulase production
      was observed within the range of 0.5-1.5 FPU g-1 DM while protease production
      showed two discrete peaks of 66 +/- 8 and 65 +/- 3 U g-1 DM at 3.5 and 48 h,
      respectively. Low sophorolipids production was also obtained, with a maximum
      yield of 0.02 g g-1 DM using hygienised digestate supplemented with external
      sugar and fat sources. Biopesticides produced by B. thuringiensis were
      successfully at 72 h of operation, reaching a maximum spore production of 8.15 +/
      0.04 (107) CFU g-1 DM and 2.85 +/- 0.22 (107) CFU g-1 DM using sterile and
      hygienised digestate, respectively. These biopesticides could contribute to the
      substitution of chemically produced pesticides, moving towards a sustainable
      digestate management in a circular economy scheme.

PMID- 30296749
TI  - Patients' perceptions and ICU clinicians predictions of quality of life following
      critical illness.
AB  - PURPOSE: To determine how patients perceive their quality of life (QOL) six
      months following critical illness and to measure clinicians' discriminative
      accuracy of predicting this outcome. MATERIALS AND METHODS: This prospective
      cohort study of intensive care unit (ICU) survivors asked patients to report
      their QOL strictly at six months compared to one month before their critical
      illness as better, the same, or worse. ICU physicians and nurses made six-month
      QOL predictions for these patients. RESULTS: Of 162 critical illness survivors,
      33% (n = 53) of patients reported six-month QOL as better, 33% (n = 54) the same,
      and 34% (n = 55) worse. Abnormal cognition and inability to return to primary
      pastime or original place of residence (p < .05 for all) were associated with
      worse self-reported QOL at six months in multivariable regression. Predictions of
      patient perceptions of QOL at six months were pessimistic and had low
      discriminative accuracy for both physicians (sensitivity 56%, specificity 53%)
      and nurses (sensitivity 49%, specificity 57%). CONCLUSIONS: Among survivors of
      critical illness, one-third each reported their six-month post-ICU QOL as better,
      the same, or worse. Self-reported six-month QOL was associated with six-month
      function. ICU clinicians should use caution in predicting self-reported QOL, as
      discriminative accuracy was poor in this cohort.

PMID- 30296750
TI  - Highly visible sepsis publications from 2012 to 2017: Analysis and comparison of
      altmetrics and bibliometrics.
AB  - PURPOSE: We sought to delineate highly visible publications related to sepsis.
      Within these subsets, elements of altmetrics performance, including mentions on
      Twitter, and the correlation between altmetrics and conventional citation counts
      were ascertained. MATERIALS AND METHODS: Three subsets of sepsis publications
      from 2012 to 2017 were synthesized by the overall Altmetric.com attention score,
      number of mentions by unique Twitter users, and conventional citation counts. For
      these subsets, geolocated Twitter activity was plotted on a choropleth, the lag
      between publication date and altmetrics mentions was characterized, and
      correlations were examined between altmetrics performance and normalized
      conventional citation counts. RESULTS: Of 57,152 PubMed query results,
      Altmetric.com data was available for 28,344 (49.6%). The top 50 publications by
      Altmetric.com attention score and Twitter attention represented a mix of original
      research and other types of work, garnering attention from Twitter users in 143
      countries that was highly contemporaneous with publication. Altmetrics
      performance and conventional citation counts were poorly correlated. CONCLUSIONS:
      While unreliable to gauge impact or future citation potential, altmetrics may be
      valuable for parties who wish to detect and drive public awareness of research
      findings and may enable researchers to dynamically explore the reach of their
      work in novel dimensions.

PMID- 30296751
TI  - Pharmacoinformatics analysis of merbarone binding site in human topoisomerase
      IIalpha.
AB  - Merbarone is a derivative of thiobarbituric acid, possessing catalytic inhibitory
      potential against human topoisomerase IIalpha (hTopoIIalpha). Merbarone was
      reported to inhibit DNA cleavage by hTopoIIalpha. It is important to understand
      the molecular mechanism of hTopoIIalpha inhibition by merbarone, as these details
      guide the rational design of new ligands. In this work, a systematic
      pharmacoinformatics analysis has been reported to analyze the merbarone
      hTopoIIalpha interactions and to identify merbarone analogs as potential
      hTopoIIalpha inhibitors. The reported crystal structure of hTopoIIalpha-DNA
      complex (PDB ID: 4FM9) is not suitable for analyzing the merbarone-binding
      domain, because it is a biological assembly of hTopoIIalpha in C-gate open
      conformation. Therefore, 3D structure of hTopoIIalpha-DNA complex suitable for
      molecular modeling analysis at merbarone binding site was first generated. Using
      this generated complex, molecular docking analysis and molecular dynamics
      simulations were performed to explore the effect of merbarone on hTopoIIalpha-DNA
      complex. The binding energy for the enol form of merbarone with hTopoIIalpha-DNA
      was estimated to be -51.28 kcal/mol. The explored binding site and identified
      molecular recognition interactions were in accordance with the previously
      reported interference in the DNA-cleavage by merbarone. Virtual screening was
      performed using drug likeness filters, toxicity filters and ADMET descriptor
      based filters followed by molecular docking (ZINC database). Sixteen compounds
      were identified as merbarone-functional analogs suitable for hTopoIIalpha
      inhibition. These identified molecules can be considered for further evaluation
      of their anti-hTopoIIalpha activity.

PMID- 30296752
TI  - First principle study of electronic, mechanical, optical and thermoelectric
      properties of CsMO3 (M = Ta, Nb) compounds for optoelectronic devices.
AB  - The electronic, mechanical, optical and thermoelectric properties of Cesium based
      perovskites CsMO3 (M = Nb, Ta) in the cubic phase has been performed through
      PBEsol-mBJ scheme in the framework of DFT. The electronic band structures and
      density of states show the studied materials having a direct band gap in the
      visible range. The mechanical stability and ductile behavior have been analyzed
      from elastic constants. Moreover, the optical behavior of the studied materials
      has been analyzed in terms of dielectric functions, refractive index, extinction
      coefficient, absorption coefficient, optical conductivity, reflectivity and
      energy loss factor. Finally, the material response with temperature has been
      elaborated by electrical conductivity, thermal conductivity, Seebeck coefficient,
      power factor, heat capacity, Hall coefficient, susceptibility and electron
      density by using BoltzTraP code. This first principle calculation of optical and
      thermoelectric properties of the novel compounds provides a new route to the
      experimentalist for the potential application in energy renewable devices.

PMID- 30296753
TI  - Enhanced adsorption of oxytetracycline to weathered microplastic polystyrene:
      Kinetics, isotherms and influencing factors.
AB  - Microplastic polystyrene foam has been found widely in the environment and is
      readily transported by wind or water. Beached and virgin foams of size 0.45-1 mm
      were prepared as sorbents to study oxytetracycline sorption. Enhanced adsorption
      were found in the beached foams compared to the virgin foams, corresponding to
      the higher specific surface area, micropore area and the degree of oxidation of
      the former. The Freundlich Kf value was 894 +/- 84 ((mg kg-1) (mg L-1)1/n) for
      oxytetracycline adsorption on the beached foams, approximately twice as high as
      on the virgin foams. Effects of solution pH on adsorption to the beached foams
      were more pronounced to the virgin foams. Maximum adsorption occurred at pH 5 at
      which electrostatic repulsion between the microplastic surface and the
      oxytetracycline zwitterion was minimal, indicating that electrostatic interaction
      may have regulated adsorption. Moreover, H-bonding and multivalent cationic
      bridging mechanisms may also have affected the adsorption of oxytetracycline to
      the beached foams as reflected by the ionic effects. Adsorption was promoted more
      in the presence of humic acid than of fulvic acid, perhaps owing to pi-pi
      conjugation between the humic acid and the microplastic surface which led to
      enhanced electrostatic attraction for oxytetracycline. This study suggests that
      weathered polystyrene foams may act as carriers of antibiotics in the environment
      and their potential risks to ecosystem and human health merit further
      investigation.

PMID- 30296754
TI  - Endocrine disruption and chronic effects of plant protection products in bees:
      Can we better protect our pollinators?
AB  - Exposure to plant protection products (PPPs) is one of the causes for the
      population decline of pollinators. In addition to direct exposure, pollinators
      are exposed to PPPs by pollen, nectar and honey that often contain residues of
      multiple PPPs. While in legislation PPPs are regarded mainly for their acute
      toxicity in bees, other effects such as neurotoxicity, immunotoxicity,
      behavioural changes, stress responses and chronic effects that may harm different
      physiologically and ecologically relevant traits are much less or not regarded.
      Despite the fact that endocrine disruption by PPPs is among key effects weakening
      survival and thriving of populations, pollinators have been poorly investigated
      in this regard. Here we summarize known endocrine disruptive effects of PPPs in
      bees and compare them to other chronic effects. Endocrine disruption in honey
      bees comprise negative effects on reproductive success of queens and drones and
      behavioural transition of nurse bees to foragers. Among identified PPPs are
      insecticides, including neonicotinoids, fipronil, chlorantraniliprole and
      azadirachtin. So far, there exists no OECD guideline to investigate possible
      endocrine effects of PPPs. Admittedly, investigation of effects on reproduction
      success of queens and drones is rarely possible under laboratory conditions. But
      the behavioural transition of nurse bees to foragers could be a possible endpoint
      to analyse endocrine effects of PPPs under laboratory conditions. We identified
      some genes, including vitellogenin, which regulate this transition and which may
      be used as biomarkers for endocrine disruptive PPPs. We plea for a better
      implementation of the adverse outcome pathway concept into bee's research and
      propose a procedure for extending and complementing current assessments,
      including OECD guidelines, with additional physiological and molecular endpoints.
      Consequently, assessing potential endocrine disruption in pollinators should
      receive much more relevance.

PMID- 30296755
TI  - Managing nutrients to mitigate soil pollution.
AB  - The health of soils is key not only to agricultural productivity, but to all the
      ecosystem services provided in terms of maintaining the quality of water, air,
      and food. Nutrient inputs to agricultural soils produce large benefits to human
      health, including the provisioning of calories and protein supporting at least
      half the human population, enhancing micronutrient bioavailability in food,
      improving crop quality, and strengthening tolerance to plant disease. With
      appropriate nutrient stewardship, such inputs contribute to soil health and
      prevent soil degradation. When mismanaged and applied inappropriately, either
      mineral or organic sources of nutrients can become pollutants both in soils and
      in water and air. The solution being embraced by industry and governments around
      the world is the implementation of principles of 4R Nutrient Stewardship,
      ensuring that the right source of nutrient is applied at the right time, in the
      right place and at the right rate.

PMID- 30296756
TI  - Salt marsh denitrification is impacted by oiling intensity six years after the
      Deepwater Horizon oil spill.
AB  - Coastal salt marshes provide the valuable ecosystem service of removing
      anthropogenic nitrogen (N) via microbially-mediated denitrification. During the
      2010 Deepwater Horizon (DWH) spill, oil exposure killed marsh plants in some
      regions and contributed to rapid compositional shifts in sediment microbial
      communities, which can impact ecosystem denitrification capacity. Within 3-5
      years of the spill, plant biomass and microbial communities in some impacted
      marshes can recover to a new stable state. The objective of this study was to
      determine whether marsh recovery 6 years after the DWH oil spill results in
      subsequent recovery of denitrification capacity. We measured denitrification
      capacity (isotope pairing technique), microbial 16S rRNA gene composition, and
      denitrifier abundance (quantitative PCR) at sites subjected to light, moderate,
      and heavy oiling during the spill that were not targeted by any clean-up efforts.
      There were no differences in plant belowground biomass, sediment extractable
      NH4+, inorganic nitrogen flux, 16S rRNA composition, 16S rRNA diversity, or
      denitrifier functional gene (nirS, norB, and nosZ) abundances associated with
      oiling status, indicating that certain drivers of ecosystem denitrification
      capacity have recovered or achieved a new stable state six years after the spill.
      However, on average, denitrification capacities at the moderately and heavily
      oiled sites were less than 49% of that of the lightly oiled site (27.7 +/- 14.7
      and 37.2 +/- 24.5 vs 71.8 +/- 33.8 MUmol N m-2 h-1, respectively). The presence
      of heavily weathered oiled residue (matched and non-matched for MC252) had no
      effect on process rates or microbial composition. The loss of function at the
      moderately and heavily oiled sites compared to the lightly oiled site despite the
      comparable microbial and environmental factors suggests that oiling intensity
      plays a role in the long-term recovery of marsh ecosystem services.

PMID- 30296757
TI  - Autophagy in testes of rats treated with bisphenol A and nonylphenol: Specific
      cellular localization and potential implications.

PMID- 30296758
TI  - Key coastal landscape structures for resilient coastal green infrastructure to
      enhance the abundance of migratory birds on the Yellow Sea.
AB  - The aim of this study was to investigate the key landscape structures of
      migratory bird habitats that affect abundance of migratory birds to promote
      resilient coastal green infrastructure planning on the Yellow Sea coast. We
      classified coastal areas into four watersheds of South Korea and conducted
      multivariate regression analysis between migratory bird populations and landscape
      structures including total class area (CA), patch area distribution (MN), patch
      density (PD), and edge density (ED). At the national level, sandbank MN, sandbank
      CA, water ED, and grasslands were derived as key landscape structures affecting
      the abundance of migratory birds. At the watershed level, key landscape
      structures were determined as follows: Urban area_MN for the Han River watershed,
      rice paddy MN for the Asan watershed, rice paddy CA for Saemangeum, and grassland
      MN for the Youngsan River watershed. Considering the multifunctionality,
      redundancy, and connectivity of the resilience strategy, we provide specific
      coastal infrastructure planning recommendations at the national and watershed
      scales.

PMID- 30296760
TI  - Characterization of Cr (VI) - Containing solid phase particles in dry dust
      deposition in Daejeon, South Korea.
AB  - Solid phase speciation of chromium in dry dust deposition and road paint was
      determined using transmission electron microscopy (TEM) and X-ray absorption
      spectroscopy (XAS). Spherical black carbon aggregates in dry dust deposition
      contained discrete nano-sized lead chromate (PbCrO4) and zinc chromate (ZnCrO4),
      which likely originated from yellow traffic paint and zinc chromate primer
      (corrosion resistant pigment), respectively based on their main applications.
      Road marking paint samples from auto roads included lead chromate particles whose
      size, shape, composition and crystal structure were similar to those in dry dust
      deposition. A slight difference was found at the particle boundary. Namely, lead
      chromate in traffic paint was encapsulated by silica-bearing matrix, while
      discrete lead chromate in the black carbon of dry deposition was rarely enclosed
      within silica-bearing matrix. The Cr K edge X-ray absorption near edge structure
      (XANES) spectrum for dry deposition showed the characteristic pre-edge resonance
      peak similar to the spectra for the Cr(VI) standard and road paint, but the lower
      intensity. The amount of Cr(VI) accounted for approximately 45% of the total Cr
      in the dust sample. The solid phase speciation of Cr observed using TEM and their
      valence states determined using XANES were consistent with the chemical
      speciation determined using the sequential extraction. The contribution of this
      study is that XANES was applied to identify Cr valance states in urban dust
      deposition and zinc chromate was found as a Cr(VI) phase in dry dust deposition
      using TEM. These study results provide novel data on Cr speciation and Cr(VI)
      containing mineral phases in dry dust deposition and their potential sources.
      Based on the wide use of lead and zinc chromate, atmospheric contamination with
      these solid phase speciation of Cr(VI) is expected in other cities in the world.

PMID- 30296759
TI  - Concentrations of perfluoroalkyl substances and bisphenol A in newborn dried
      blood spots and the association with child behavior.
AB  - Experimental studies suggest that prenatal exposure to endocrine disrupting
      chemicals interferes with developmental processes in the fetal brain. Yet,
      epidemiological evidence is inconclusive. In a birth cohort (2008-2010, upstate
      New York), we quantified concentrations of perfluorooctane sulfonic acid (PFOS),
      perfluorooctanoic acid (PFOA), and bisphenol A (BPA) in stored newborn dried
      blood spots using liquid chromatography/tandem mass spectrometry. Mothers
      reported on children's behavior using the Strengths and Difficulties
      Questionnaire at age 7 (650 singletons and 138 twins). Difficulties in total
      behavior (i.e., emotional, conduct, hyperactivity, and peer problems) and
      prosocial behavior were classified using validated cut-offs. We used logistic
      regression with generalized estimating equations to estimate the odds of having
      difficulties per exposure category. In total, 111 children (12.1%) had total
      behavioral difficulties and 60 (6.5%) had difficulties in prosocial behavior. The
      median (interquartile range) of PFOS, PFOA, and BPA were 1.74 ng/ml (1.33), 1.12
      ng/ml (0.96), and 7.93 ng/ml (10.79), respectively. Higher PFOS levels were
      associated with increased odds of having behavioral difficulties (OR per SD of
      log PFOS = 1.30, 95%CI: 1.03-1.65). We observed associations between PFOS in the
      highest relative to the lowest quartile and behavioral difficulties (OR for
      PFOS1.14-1.74 = 1.65, 95%CI: 0.84-3.34; PFOS1.75-2.47 = 1.73, 95%CI: 0.87-3.43;
      and PFOS>2.47 = 2.47, 95%CI: 1.29-4.72 compared to PFOS<1.41). The associations
      between higher concentrations of PFOS and behavioral difficulties at age 7 years
      were driven by problems in conduct and emotional symptoms. Higher PFOA levels
      were associated with difficulties in prosocial behavior (OR = 1.35, 95%CI: 1.03
      1.75). There was an inverse association between BPA concentrations and
      difficulties in prosocial behavior but only in the 2nd and 4th quartiles. We
      found no interactions between sex and chemical concentrations. Increasing
      prenatal exposure to PFOS and PFOA, as reflected in neonatal concentrations, may
      pose risk for child behavioral difficulties.

PMID- 30296761
TI  - Short-term effect of heat waves on hospital admissions in Madrid: Analysis by
      gender and comparision with previous findings.

PMID- 30296762
TI  - RNA-sequencing to assess the health of wild yellow perch (Perca flavescens)
      populations from the St. Lawrence River, Canada.
AB  - This study aimed to better understand in situ cumulative effects of anthropogenic
      stressors on the health of St. Lawrence River (QC, Canada) yellow perch
      populations using high-throughput transcriptomics and a multi-biological level
      approach. Fish were collected in the upstream fluvial Lake Saint-Francois (LSF)
      with low degree of environmental perturbations; Lake Saint-Louis (LSL) considered
      having a moderate degree of anthropogenic stressors, and Lake Saint-Pierre (LSP)
      a sector where the perch population has been severely declining. Morphometric
      results indicated that fish from the downstream LSP showed lower body condition
      compared to LSF and LSL. Liver transcriptomic responses were assessed by RNA
      sequencing. Two hundred and eighty genes were over-transcribed in LSP perch while
      200 genes were under-transcribed compared to LSF and LSL. In LSP fish, genes
      transcripts related to reproduction, retinol, iron, thyroid hormones, oxidative
      stress, lipid metabolism and immune functions were among the most abundant
      suggesting that multiple metabolic and physiological pathways were impacted by
      environmental stressors at this site. Inhibition of liver superoxide dismutase,
      catalase and glutathione S-transferase activities were also observed at the
      cellular level. Overall, identified impacted biological pathways in perch from
      LSP may help understand the precarious state of this population and identify the
      factors inhibiting its recovery.

PMID- 30296763
TI  - Dual impact of dissolved organic matter on cytotoxicity of PVP-Ag NPs to
      Escherichia coli: Mitigation and intensification.
AB  - Cytotoxicity of silver nanoparticles (Ag NPs) is attributed to silver
      internalization, which can be depressed by dissolved organic matter (DOM) to form
      Ag-DOM. Ag-DOM are bioavailable and then silver internalization could be
      increased. Herein, 3 and 48-h Escherichia coli viability bioassays were employed
      to evaluate effect of fulvic acid and humic acid (10 mg L-1) on cytotoxicity of
      30 and 100 nm PVP-Ag NPs. Moreover, zebrafish embryos were used as reference
      model to understand silver internalization routes. Ag ions or Ag-DOM
      internalization varied in routes to Escherichia coli and zebrafish embryos.
      Cytotoxicity mechanisms of PVP-Ag NPs are dynamic. In 3-h bioassays, cytotoxicity
      of PVP-Ag NPs mainly involves Ag particle-related toxicity. DOM significantly
      mitigated cytotoxicity of PVP-Ag NPs (p < 0.05) through adhering on surface of
      PVP-Ag NPs. Ag ions or Ag-DOM were hardly internalized into Escherichia coli
      cells during 3-h exposures duration. In 48-h bioassays, cytotoxicity of PVP-Ag
      NPs is dependent on Ag ion-related and particle-related toxicity. Silver was
      internalized into Escherichia coli via Ag-DOM consumption as an indirect route.
      Thus, DOM promoted silver internalization into Escherichia coli but not into
      zebrafish embryos, significantly intensifying cytotoxicity (p < 0.05). The
      results suggested DOM has a dual impact on cytotoxicity of PVP-Ag NPs: mitigation
      and intensification. For risk assessment, it should be considered that
      cytotoxicity mechanisms of PVP-Ag NPs are dynamic and threats can be intensified
      by DOM during prolonged exposure.

PMID- 30296764
TI  - Pre-ozonation of source water: Assessment of efficacy against Giardia duodenalis
      cysts and effects on natural organic matter.
AB  - The protozoan Giardia duodenalis is one of the parasites of primary concern in
      drinking water treatment plants, due to its resistance to chlorination. Another
      matter of concern regarding chlorination of drinking water is the formation of
      disinfection by-products in the presence of precursors such as natural organic
      matter (NOM). In this study, the effects of ozonation (5 mg L-1) on G. duodenalis
      cysts in raw surface water from a drinking water treatment plant were evaluated,
      and the presence and alteration of NOM were assessed, as an indicative of the
      potential to prevent total organic halogen (TOX) formation during post
      chlorination. Following ozone treatment, the presence of damaged cysts was
      observed by direct immunofluorescence assay (IFA) and confirmed by the molecular
      approach propidium monoazide-polymerase chain reaction (PMA-PCR). Using an animal
      model, analysis of the intestinal tissues revealed that 80% of the animals
      inoculated with ozonated water were positive for trophozoites. This study shows
      that analysis of intestinal fragments is imperative to accurately assess animal
      infection following inoculation of treated cysts. More importantly, considering
      the low infective dose of Giardia cysts in susceptible hosts, an ozone dosage
      usually applied in drinking water treatment plants did not completely inactivate
      G. duodenalis cysts in surface water. Nonetheless, the results suggest that
      competitive reactions with NOM have occurred, and the applied ozone dosage has
      proven useful to remove NOM reactivity, and thus prevent halogenated DBP
      formation during post-chlorination.

PMID- 30296765
TI  - Metabolomics reveals defensive mechanisms adapted by maize on exposure to high
      molecular weight polycyclic aromatic hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons are an important group of persistent organic
      pollutants. Using plants to remediate PAHs has been recognized as a cost
      effective and environmentally friendly technique. However, the overall impact of
      PAHs on the regulation of plant metabolism has not yet been explored. In this
      study, we analyzed the alteration in the maize (Zea mays L.) metabolome on
      exposure to high molecular weight PAHs such as benzo[a]pyrene (BaP) and pyrene
      (PYR) in a hydroponic medium, individually and as a mixture (BaP + PYR) using GC
      MS. The differences in the metabolites were analyzed using XCMS (an acronym for
      various forms (X) of chromatography-mass spectrometry), an online-based data
      analysis tool. A significant variation in metabolites was observed between
      treatment groups and the unspiked control group. The univariate, multivariate and
      pathway impact analysis showed there were more significant alterations in
      metabolic profiles between individual PAHs and the mixture of BaP and PYR. The
      marked changes in the metabolites of galactose metabolism and aminoacyl tRNA
      biosynthesis in PAHs treated maize leaves exhibit the adaptive defensive
      mechanisms for individual and PAHs mixture. Therefore, the metabolomics approach
      is essential for an understanding of the complex biochemical responses of plants
      to PAHs contaminants. This knowledge will shed new light in the field of
      phytoremediation, bio-monitoring, and environmental risk assessment.

PMID- 30296766
TI  - A density functional theory study of the molecular interactions between a series
      of amides and sulfuric acid.
AB  - Amides, a class of nitrogen-containing organic pollutants in the atmosphere, may
      affect the formation of atmospheric aerosols by the interactions with sulfuric
      acid. Here, the molecular interactions of sulfuric acid with formamide,
      methylformamide, dimethylformamide, acetamide, methylacetamide and
      dimethylacetamide was investigated by density functional theory. Geometry
      optimization and Gibbs free energy calculation were carried out at M06-2X/6
      311++G(3df,3pd) level. The results indicate that the addition of amides to H2SO4
      might have a promoting effect on atmospheric new particle formation at 298.15 K
      and 1 atm. In the initial stage of new particle formation, the binding capacity
      of amides and sulfuric acid is stronger than ammonia, but weaker than
      methylamine. It is worth noting that the trans-methylacetamide could have similar
      capabilities of stabilizing sulfuric acid as dimethylamine. In the presence of
      water, amides are found to only have a weak enhancement capability on new
      particle formation. In addition, we can infer from evaporation rate that the
      small molecule clusters of formamide and sulfuric acid may be more energetically
      favorable than macromolecule clusters.

PMID- 30296767
TI  - Metal/metalloid levels in urine and seminal plasma in relation to computer-aided
      sperm analysis motion parameters.
AB  - BACKGROUND: Exposure to high levels of metals/metalloids may impair semen
      quality. Computer-aided sperm analysis (CASA) can be used for kinematic analysis
      of spermatozoa, which provides additional insights into sperm motion
      characteristics. OBJECTIVE: To explore the associations of urinary and seminal
      plasma metal/metalloid concentrations with CASA motion parameters and assess the
      degree of correspondence between the two sample types. METHODS: Eighteen
      metals/metalloids in seminal plasma and repeated urine samples were determined
      among 746 men recruited from a reproductive center. We assessed their
      associations with 6 CASA motion parameters [i.e., straight-line velocity (VSL),
      curvilinear velocity (VCL), average path velocity (VAP), linearity (LIN),
      straightness (STR) and amplitude head displacement (ALH)] using multivariable
      linear regression models. RESULTS: We found significantly inverse dose-dependent
      relationships between seminal plasma arsenic (As) and VSL, VCL and VAP, between
      seminal plasma selenium (Se) and VSL and VAP, between seminal plasma zinc (Zn)
      and STR and LIN, and between seminal plasma manganese (Mn) and LIN in single
      metal models [all false discovery rate (FDR) adjusted P for trend < 0.05]. These
      dose-response relationships remained statistically significant based on multiple
      metal models and restricted cubic spline functions. Metal/metalloid
      concentrations in urine poorly predicted the same-day seminal plasma
      concentrations [coefficient of determination (R2) < 0.15]. We didn't find any
      significant associations between urinary metal/metalloid concentrations and the
      CASA motion parameters. CONCLUSION: Exposure to high levels of As, Se, Mn and Zn
      may impair sperm motion capacity. Concentrations of metals/metalloids in spot
      urine samples cannot accurately predict same-day seminal plasma exposure levels.

PMID- 30296768
TI  - Monitoring transformation product formation in the drinking water treatments
      rapid sand filtration and ozonation.
AB  - Transformation products (TPs) can be formed from organic micropollutants in the
      water cycle through both biological and technological processes. Despite the TPs'
      potentially altered toxicity compared to their parent compounds, transformation
      processes are not routinely monitored, and in particular those induced by
      drinking water treatment remain elusive. This lack of information is mainly due
      to the technical challenges in analyzing TPs, which are often unknown compounds
      occurring in low concentrations. Their analysis requires sophisticated analytical
      techniques such as non-target screening (NTS) based on high-resolution tandem
      mass spectrometry (HRMS/MS) methods combined with novel data analysis approaches.
      Here, we addressed the challenges of TP analysis and the scarcity of TP research
      concerning studies in drinking water. We performed lab-scale experiments to
      monitor TP formation of three organic micropollutants prevalent in drinking water
      sources, i.e. carbamazepine, clofibric acid and metolachlor, during rapid sand
      filtration and ozonation, two readily applied biotic and abiotic drinking water
      treatments, respectively. To facilitate TP identification in the NTS data,
      halogenated and/or isotopically labeled parent compounds were used, revealing
      potential TPs through their isotopic patterns. The experimental results showed
      that degradation of the parent compounds and TP formation were treatment and
      compound specific. In silico TP prediction and literature mining enabled suspect
      screening of the non-target data and thereby significantly enhanced TP
      identification. Overall, the developed workflow enables an efficient and more
      comprehensive assessment of drinking water quality changes during water
      treatment.

PMID- 30296769
TI  - Monetized health benefits attributable to mobile source emission reductions
      across the United States in 2025.
AB  - By-products of mobile source combustion processes, such as those associated with
      gasoline- and diesel-powered engines, include direct emissions of particulate
      matter as well as precursors to particulate matter and ground-level ozone. Human
      exposure to fine particulate matter with an aerodynamic diameter smaller than 2.5
      MUm (PM2.5) is associated with increased incidence of premature mortality and
      morbidity outcomes. This study builds upon recent, detailed source-apportionment
      air quality modeling to project the health-related benefits of reducing PM2.5
      from mobile sources across the contiguous U.S. in 2025. Updating a previously
      published benefits analysis approach, we develop national-level benefit per ton
      estimates for directly emitted PM2.5, SO2/pSO4, and NOX for 16 mobile source
      sectors spanning onroad vehicles, nonroad engines and equipment, trains, marine
      vessels, and aircraft. These benefit per ton estimates provide a reduced-form
      tool for estimating and comparing benefits across multiple mobile source emission
      scenarios and can be applied to assess the benefits of mobile source policies
      designed to improve air quality. We found the benefit per ton of directly emitted
      PM2.5 in 2025 ranges from $110,000 for nonroad agriculture sources to $700,000
      for onroad light duty gas cars and motorcycles (in 2015 dollars and based on an
      estimate of PM-related mortality derived from the American Cancer Society cohort
      study). Benefit per ton values for SO2/pSO4 range from $52,000 for aircraft
      sources (including emissions from ground support vehicles) to $300,000 for onroad
      light duty diesel emissions. Benefit per ton values for NOX range from $2100 for
      C1 and C2 marine vessels to $7500 for "nonroad all other" mobile sources,
      including industrial, logging, and oil field sources. Benefit per ton estimates
      increase approximately 2.26-fold when using an alternative concentration response
      function to derive PM2.5-related mortality. We also report benefit per ton values
      for the eastern and western U.S. to account for broad spatial heterogeneity
      patterns in emissions reductions, population exposure and air quality benefits.

PMID- 30296770
TI  - The effect of transportation vibration on the urban acoustic environment.

PMID- 30296772
TI  - Macroinvertebrate community responses to river impoundment at multiple spatial
      scales.
AB  - River impoundment by the construction of dams potentially modifies a wide range
      of abiotic and biotic factors in lotic ecosystems and is considered one of the
      most significant anthropogenic impacts on rivers globally. The past two decades
      have witnessed a growing body of research centred on quantifying the effects of
      river impoundment, with a focus on mitigating and managing the effects of
      individual large dams. This study presents a novel multi-scale comparison of
      paired downstream and control sites associated with multiple water supply
      reservoirs (n = 80) using a spatially extensive multi-year dataset.
      Macroinvertebrate community structure and indices were analysed in direct
      association with spatial (e.g. region) and temporal variables (e.g. season) to
      identify consistent patterns in ecological responses to impoundment.
      Macroinvertebrate communities at monitoring sites downstream of water supply
      reservoirs differed significantly from those at control sites at larger spatial
      scales, both in terms of community structure and taxa richness. The effect was
      most significant at the regional scale, while biogeographical factors appeared to
      be important drivers of community differences at the national scale. Water supply
      reservoirs dampened natural seasonal patterns in community structure at sites
      downstream of impoundments. Generally, taxonomic richness was higher and %EPT
      richness lower at downstream sites. Biomonitoring indices used for river
      management purposes were able to detect community differences, demonstrating
      their sensitivity to river regulation activities. The results presented improve
      our understanding of the spatially extensive and long-term effects of water
      supply reservoirs on instream communities and provide a basis for the future
      implementation of mitigation measures on impounded rivers and heavily modified
      waterbodies.

PMID- 30296771
TI  - Ambient air pollution and fetal growth restriction: Physician diagnosis of fetal
      growth restriction versus population-based small-for-gestational age.
AB  - BACKGROUND: Ambient air pollution may affect fetal growth restriction (FGR)
      through several mechanisms. However, prior studies of air pollution and small-for
      gestational age (SGA), a common proxy for FGR, have reported inconsistent
      findings. OBJECTIVE: We assessed air pollution in relation to physician-diagnosed
      FGR and population-based SGA in the Eunice Kennedy Shriver National Institute of
      Child Health and Human Development (NICHD) Consecutive Pregnancy Study (2002
      2010). METHODS: Among 50,005 women (112,203 singleton births), FGR was captured
      from medical records and ICD-9 codes, and SGA determined by population standards
      for birthweight <10th, <5th and <3rd percentile. Community Multiscale Air Quality
      models estimated ambient levels of seven criteria pollutants for whole pregnancy,
      3-months preconception, and 1st, 2nd and 3rd trimesters. Generalized estimating
      equations with robust standard errors accounted for interdependency of
      pregnancies within participant. Models adjusted for maternal age, race/ethnicity,
      pre-pregnancy body mass index, smoking, alcohol, parity, insurance, marital
      status, asthma and temperature. RESULTS: FGR was diagnosed in 1.5% of infants,
      and 6.7% were <10th, 2.7% <5th and 1.5% <3rd percentile for SGA. Positive
      associations of SO2, NO2 and PM10 and negative associations of O3 with FGR were
      observed throughout preconception and pregnancy. For example, an interquartile
      increase in whole pregnancy SO2 was associated with 16% (95% CI 8%, 25%)
      increased FGR risk, 17% for NO2 (95% CI 9%, 26%) and 12% for PM10 (95% CI 6%,
      19%). Associations with SGA were less clear. CONCLUSIONS: Chronic exposure to air
      pollution may be associated with FGR but not SGA in this low-risk population.

PMID- 30296773
TI  - Effects of vegetation restoration on soil quality in degraded karst landscapes of
      southwest China.
AB  - Vegetation restoration was implemented to control soil erosion in the karst
      regions of southwest China. It is essential to assess the soil function and
      quality scientifically during this process and to adopt suitable management
      practices for this area. However, few studies have been conducted to
      comprehensively evaluate the effect of vegetation restoration on soil quality in
      this severely eroded karst area. By taking 302 soil samples from 11 vegetation
      types, this study investigated the influence of different types of vegetation
      restoration on soil quality using an integrated soil quality index (SQI) and a
      generalized linear model (GLM). Vegetation types had significant effects on soil
      properties and thus on soil quality. SQI was developed by using TN, TP, TK, AP,
      and clay content; TN had highest weighting values (0.58), which indicated that it
      contributed the most to final SQI. The highest and lowest SQI values were
      observed for primary forest and cropland, respectively. Overall, vegetation
      restoration (e.g., natural restoration, artificial forests and artificial
      grassland) improved soil quality significantly. A GLM model explained 73.20% of
      the total variation in SQI, and vegetation type explained the largest proportion
      (46.39%) of the variation, which implies that the vegetation restoration
      practices can greatly enhance the soil quality in karst landscapes of southwest
      China. The results of this study may be used to improve implication of ecological
      restoration and management in degraded regions.

PMID- 30296774
TI  - Response of plant production to growing/non-growing season asymmetric warming in
      an alpine meadow of the Northern Tibetan Plateau.
AB  - A field growing/non-growing season asymmetric warming experiment (C: control,
      i.e., no warming in the entire year; GLNG: growing season warming lower than non
      growing season warming; GHNG: growing season warming higher than non-growing
      season warming) was conducted in an alpine meadow of the Northern Tibetan Plateau
      in early June 2015. The effects of growing/non-growing season asymmetric warming
      on the normalized difference vegetation index (NDVI), soil adjusted vegetation
      index (SAVI), aboveground biomass (AGB) and gross primary production (GPP) in
      2015-2017 were examined. The 'GLNG' and 'GHNG' treatments significantly increased
      the annual mean air temperature (Ta) by 2.95  degrees C and 2.76  degrees C, and
      the vapor pressure deficit (VPD) by 0.23 kPa and 0.28 kPa but significantly
      reduced the annual mean soil moisture (SM) by 0.02 m3 m-3 and 0.02 m3 m-3
      respectively; however, changes in the annual mean Ta, VPD and SM were the same
      between the 'GLNG' and 'GHNG' treatments over the three years in 2015-2017. There
      were no significant differences in the SAVI and GPP among the 'C', 'GLNG' and
      'GHNG' treatments over the three growing seasons in 2015-2017. The 'GLNG' and
      'GHNG' treatments did not significantly affect the NDVI and AGB compared to 'C',
      whereas the NDVI and AGB under the 'GLNG' treatment were significantly greater
      than those under the 'GHNG' treatment over the three growing seasons in 2015
      2017. The significant differences in NDVI and AGB between the 'GLNG' and 'GHNG'
      treatments may be attributed to the different effects under the 'GLNG' and 'GHNG'
      treatments on the non-growing season Ta, growing season water availability and
      soil nitrogen availability. Therefore, the non-growing season with a higher
      warming magnitude may have stronger effects on the aboveground plant production
      than did the growing season with a higher warming magnitude in the alpine meadow
      of the Northern Tibetan Plateau.

PMID- 30296775
TI  - Impacts of climate change on streamflow and sediment concentration under RCP 4.5
      and 8.5: A case study in Purna river basin, India.
AB  - Climate change has a significant effect on various hydrological processes in a
      large river basin. The assessment of these processes is also useful for water
      resource management and long-term sustainability of any hydrological project. In
      this study, an attempt is made to quantify the effects of climate change on
      streamflow and sediment concentration in the Purna river basin, India. Three
      Regional Circulation Models (RCMs) with two Representative Concentration Pathways
      (RCPs) 4.5 and 8.5 for the four future periods of P1 (2009-2031), P2 (2032-2053),
      P3 (2054-2075) and P4 (2076-2099) are considered. Differences in scenarios are
      compared with the base period 1980-2005. The SWAT is used on monthly basis for
      the period 1980 to 2005 with calibration period 1980 to 1994 and validation
      period 1995 to 2005. The projected precipitation and temperature show a
      significant increasing trend compared to the baseline condition for both RCPs.
      Similarly, the average monthly streamflow is projected to increase by 24.47 to
      115.94m3/s whereas average monthly sediment concentration by 32.58 to 162.96mg/l
      under RCP 4.5 and 8.5. In particular, streamflow and sediment are expected to
      increase significantly from June to September at the outlet of the basin. The
      study results give insight into future hydrological scenarios which will be
      useful for policy makers to implement effective water resource strategies.

PMID- 30296776
TI  - Protein-specific distribution patterns of perfluoroalkyl acids in egg yolk and
      albumen samples around a fluorochemical facility.
AB  - In this study, eggs from free-range and barn chickens in farms around a
      fluorochemical facility were collected to assess the distribution profiles of
      perfluoroalkyl acids (PFAAs), including isomers of perfluorooctane sulfonate
      (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS), in
      egg yolk and albumen. The results revealed that the concentrations of PFAAs in
      yolks were significantly higher than those in albumen. All 17 PFAAs examined
      could be detected in yolks, showing decreasing concentrations with increasing
      distance from the fluorochemical facility. The three predominant compounds in
      yolks were perfluorobutanoic acid (PFBA, mean concentration 81.4 ng/g ww), PFOS
      (28.0 ng/g ww), and PFOA (4.83 ng/g ww), and this result is consistent with the
      product structure of the facility. Moreover, n-PFOA, n-PFOS, and n-PFHxS were the
      dominant contaminants in yolk, with mean concentrations of 4.75, 25.7, and 4.29
      ng/g ww, respectively. In albumen, PFBA was still the predominant PFAA congener
      (mean concentration = 3.93 ng/g ww), followed by PFOA. Docking analysis indicated
      that the PFAAs presented higher binding abilities with the low density
      lipoprotein, high density lipoprotein, and vitellin proteins in yolk than that
      with ovalbumin albumen proteins, which might be the main factor influencing the
      possible difference in distributions of PFAAs in yolk and albumen.

PMID- 30296777
TI  - Diversification of forest management regimes secures tree microhabitats and bird
      abundance under climate change.
AB  - The loss of biodiversity in temperate forests due to combined effect of climate
      change and forest management poses a major threat to the functioning of these
      ecosystems in the future. Climate change is expected to modify ecological
      processes and amplify disturbances, compromising the provisioning of multiple
      ecosystem services. Here we investigate the impacts of climate change and forest
      management on the abundance of tree microhabitats and forest birds as
      biodiversity proxies, using an integrated modelling approach. To perform our
      analysis, we calibrated tree microhabitat and bird abundance in a forest
      landscape in Southwestern Germany, and coupled them with a climate sensitive
      forest growth model. Our results show generally positive impacts of climate
      warming and higher harvesting intensity on bird abundance, with up to 30%
      increase. Conversely, climate change and wood removals above 5% of the standing
      volume led to a loss of tree microhabitats. A diversified set of management
      regimes with different harvesting intensities applied in a landscape scale was
      required to balance this trade-off. For example, to maximize the expected bird
      abundance (up to 11%) and to avoid tree microhabitat abundance loss of >20%
      necessitates setting aside 10.2% of the forest area aside and application of
      harvesting intensities < 10.4% of the standing volume. We conclude that promoting
      forest structural complexity by diversifying management regimes across the
      landscape will be key to maintain forest biodiversity in temperate forests under
      climate change.

PMID- 30296778
TI  - Assessing pH-dependent toxicity of fluoxetine in embryonic zebrafish using mass
      spectrometry-based metabolomics.
AB  - While it is well known that fluoxetine is more toxic to aquatic organisms at high
      pH, the metabolic dysregulations related to observed pH-dependent effects are
      still poorly understood. In the present study, we utilized a gas chromatography
      mass spectrometry (GC-MS) based metabolomics approach to assess metabolomic
      profile changes in developing zebrafish embryos following exposure (2 hpf-96 hpf)
      to different concentrations of fluoxetine at three environmentally relevant pH
      values (7.0, 8.0, and 9.0). Multivariate data analyses and pathway analyses were
      used to assess metabolomic profile changes and elicit important biochemical
      information regarding pH-dependent toxicity of fluoxetine. Overall, the affected
      biochemical functions related to fluoxetine exposure included amino acid
      metabolism, energy metabolism, nitrogenous waste excretion and osmolyte
      functions. While fluoxetine exposure (56 MUg/L, 70 MUg/L and 500 MUg/L) caused no
      significant changes at pH 7, 500 MUg/L and 70 MUg/L fluoxetine was differentiated
      from the controls at pH 8 and pH 9 respectively. Three, eight and seven
      metabolites were identified as the most adversely affected at pH 7, 8 and 9,
      respectively. The altered metabolites associated with fluoxetine toxicity at high
      pH included urea, glycine and d-glucose 6-phosphate. Exposure to 70 MUg/L
      fluoxetine, did not cause significant metabolomic profile changes at pH 7,
      However, the results indicate that this exposure concentration at pH and 9 can
      cause significant metabolic dysregulation related to apoptosis and oxidative
      stress. Increasing aqueous pH progressively enhanced fluoxetine induced toxicity
      for the 70 MUg/L exposure group. The observed impacts included higher energy
      consumption at pH 7, a breakdown of reserve energy to supplement energy demand at
      pH 8 and impaired lipid metabolism at pH 9. This study provides important
      information regarding molecular-level effects related to pH-dependent exposure of
      fluoxetine in embryonic zebrafish.

PMID- 30296779
TI  - Efficient GPU-based Monte-Carlo simulation of diffusion in real astrocytes
      reconstructed from confocal microscopy.
AB  - The primary goal of this work is to develop an efficient Monte-Carlo simulation
      of diffusion-weighted signal in complex cellular structures, such as astrocytes,
      directly derived from confocal microscopy. In this study, we first use an octree
      structure for spatial decomposition of surface meshes. Octree structure and
      radius-search algorithm help to quickly identify the faces that particles can
      possibly encounter during the next time step, thus speeding up the Monte-Carlo
      simulation. Furthermore, we propose to use a three-dimensional binary marker to
      describe the complex cellular structure and optimize the particle trajectory
      simulation. Finally, a GPU-based version of these two approaches is implemented
      for more efficient modeling. It is shown that the GPU-based binary marker
      approach yields unparalleled performance, opening up new possibilities to better
      understand intracellular diffusion, validate diffusion models, and create
      dictionaries of intracellular diffusion signatures.

PMID- 30296780
TI  - Calculating Standard Kt/V during Hemodialysis Based on Urea Mass Removed.
AB  - BACKGROUND/AIMS: We derived a novel equation for calculating weekly urea standard
      Kt/V (stdKt/V) during hemodialysis (HD) based on urea mass removed, comparable to
      the approach during peritoneal dialysis. METHODS: Theoretical consideration of
      urea mass balance during HD led to the following equation for stdKt/V, namely,
      stdKt/V = N * (URR + UFV/V), where N is the number of treatments per week, URR is
      urea reduction ratio per treatment, UFV is ultrafiltration volume per treatment,
      and V is postdialysis urea distribution volume. URR required corrections for
      postdialysis rebound and intradialytic urea generation. We compared the accuracy
      of this approach with previous equations for stdKt/V by numerical simulations
      using a 2-compartment model of urea kinetics for thrice-weekly and more frequent
      HD prescriptions. RESULTS: The proposed equation based on urea mass removed
      predicted values of stdKt/V that are equivalent to those calculated by previous
      equations for stdKt/V. CONCLUSION: This work provides a novel approach for
      calculating stdKt/V during HD and strengthens the theoretical understanding of
      stdKt/V.

PMID- 30296781
TI  - A Rare Case of Concomitant Deletions in 15q11.2 and 19p13.3.
AB  - A female individual with concomitant deletions in 15q11.2 and 19p13.3 is
      reported. She presents facial dysmorphisms, motor delay, learning difficulties,
      and mild behavioral impairment. After chromosomal microarray analysis, the final
      karyotype was established as 46,XX.arr[GRCh37] 15q11.2
      (22770421_23282798)*1,19p13.3(3793904_4816330)*1. The deletion in 15q11.2 is 507
      kb in size involving 7 non-imprinted genes, 4 of which are registered in the OMIM
      database and are implicated in neuropsychiatric or neurodevelopmental disorders.
      The deletion in 19p13.3 is 1,022 kb in size and encompasses 47 genes, most of
      which do not have a well-known function. The genotype-phenotype correlation is
      discussed, and most of the features could be related to the 19p13.3 deletion,
      except for velopharyngeal insufficiency. Other genes encompassed in the deleted
      region, as well as unrecognized epistatic factors could also be involved.
      Nevertheless, the two-hit model related to the 15q11.2 deletion would be an
      important hypothesis to be considered.

PMID- 30296782
TI  - The Anticancer Effect of Huaier Extract in Renal Cancer 786-O Cells.
AB  - BACKGROUND: Trametes robiniophila Murr (Huaier) has been used as an adjuvant
      therapy of tumor in traditional Chinese medicine for many years, but the
      underlying mechanisms are largely unknown. In the present study, we tested the
      inhibitory effect of Huaier extract on renal cancer 786-O cells and explored the
      possible mechanisms. METHODS: 786-O cells were treated by gradient concentrations
      of Huaier extract, cell viability, invasion, migration and apoptosis were
      assessed by cell counting kit 8, cell scratch, transwell, and flow cytometry
      assay in vitro. The changes in protein level were detected by western blot
      analysis. Finally, the anticancer effect of Huaier was tested in vivo by nude
      mouse tumorigenicity assay. RESULTS: Viability of 786-O cells was suppressed by
      Huaier in a time- and dose-dependent manner; cell invasion and migration were
      also dramatically inhibited. Flow cytometry assays showed that Huaier could
      induce cell apoptosis. Western blotting analysis indicated that Huaier suppressed
      the activation of PI3K/AKT/mTOR/p70S6K/4E-BP1 signaling pathway. We also found
      that Huaier could partly reverse the epithelialmesenchymal transition (EMT)
      process. In vivo experiment indicated that tumor growth in the xenograft mouse
      model was suppressed by Huaier. CONCLUSION: Huaier plays an anticancer effect
      partially through the suppression of the PI3K/AKT/mTOR/p70S6K/4E-BP1 pathway and
      by reversing the EMT process. Huaier may act as an effective agent for treating
      renal cell carcinoma.

PMID- 30296783
TI  - Meiotic Recombination Differences in Rams from Three Breeds of Sheep in the US.
AB  - Meiotic recombination is an important contributor to genetic variation and
      ensures proper chromosome segregation during gametogenesis. Previous studies
      suggest that at least 1 crossover (CO) per chromosome arm is important to avoid
      mis-segregation. While the total number of COs per spermatocyte is known to
      differ in mice, this is only beginning to be evaluated in sheep. This study used
      a cytogenetic approach to quantify and compare the number of COs per spermatocyte
      in rams from 3 breeds of sheep: Suffolk, Icelandic, and Targhee. In total, 2,758
      spermatocytes and over 170,000 COs were examined. Suffolk rams exhibited the
      lowest mean number of COs (61.1 +/- 0.15) compared to Icelandic (63.5 +/- 0.27)
      and Targhee (65.9 +/- 0.26) rams. Significant differences in the number of COs
      per spermatocyte were observed between Suffolk, Icelandic, and Targhee breeds as
      well as within each breed. Additionally, the number and location of COs were
      characterized for homologous chromosomes in a subset of spermatocytes for each
      ram. A positive correlation was identified between the number of COs and the
      length of the homologous chromosome pair. Suffolk and Icelandic rams exhibited up
      to 7 COs per chromosome, while Targhee rams exhibited up to 9. Further, distinct
      CO location preferences on homologous chromosome pairs with 1, 2, 3, and 4 COs
      were observed in all 3 breeds. These data in sheep will aid in elucidating the
      mechanism of mammalian meiotic recombination, an important contributor to genetic
      diversity.

PMID- 30296784
TI  - The Relationship between Maxillary Sinus Lateral Wall Thickness, Alveolar Bone
      Loss, and Demographic Variables: A Cross-sectional Cone Beam Computerized
      Tomography Study.
AB  - OBJECTIVES: Sinus floor evelation and augmentation surgery is widely used as a
      reliable procedure to increase insufficient bone height in the posterior
      maxillary area. The purpose of the present clinical study was to determine the
      associations between periodontal bone loss (PBL), maxillary sinus lateral bone
      wall thickness, age, and gender using cone beam computerized tomography (CBCT).
      MATERIAL AND METHOD: The current retrospective study consists of 716 maxillary
      sinus CBCT images of 358 patients. The CBCT scans were assessed to detect the
      relationship between lateral wall thickness and PBL. ANOVA and student t test
      analysis were used to determine the influence of PBL on sinus lateral wall
      thickness. RESULTS: Sinus lateral wall thickness was significantly associated
      with PBL (p < 0.05) at 3 mm, 13 mm and 15 mm height. There was no significant
      association between lateral wall thickness and gender (p > 0.05). However, there
      was a significant association between lateral wall thickness at 3 mm and 13 mm
      and age (p < 0.05). There were significant associations between the PBL and age
      (p < 0.001), and PBL and gender (p < 0.05). CONCLUSION: PBL might have an
      association with maxillary sinus lateral bone wall thickness. Further studies are
      needed to confirm this possible relationship.

PMID- 30296785
TI  - A Comparison of Simple Analytical Methods for Determination of Fluoride in
      Microlitre-Volume Plasma Samples.
AB  - : The aim was to compare potential methods for fluoride analysis in microlitre
      volume plasma samples containing nano-gram amounts of fluoride. METHODS: A group
      of 4 laboratories analysed a set of standardised biological samples as well as
      plasma to determine fluoride concentration using 3 methods. In Phase-1, fluoride
      analysis was carried out using the established hexamethyldisiloxane (HMDS)
      diffusion method (1 mL-aliquot/analysis) to obtain preliminary measurement of
      agreement between the laboratories. In Phase-2, the laboratories analysed the
      same samples using a micro-diffusion method and known-addition technique with 200
      uL-aliquot/analysis. Coefficients of Variation (CVs) and intra-class correlation
      coefficients (ICCs) were estimated using analysis of variance to evaluate the
      amount of variation within- and between-laboratories. Based on the results of the
      Phase-2 analysis, 20 human plasma samples were analysed and compared using the
      HMDS-diffusion method and known-addition technique in Phase-3. RESULTS:
      Comparison of Phase-1 results showed no statistically significant difference
      among the laboratories for the overall data set. The mean between- and within
      laboratory CVs and ICCs were < 0.13 and >=0.99, respectively, indicating very low
      variability and excellent reliability. In Phase-2, the overall results for
      between-laboratory variability showed a poor CV (1.16) and ICC (0.44) for the
      micro-diffusion method, whereas with the known-addition technique the
      corresponding values were 0.49 and 0.83. Phase-3 results showed no statistically
      significant difference in fluoride concentrations of the plasma samples measured
      with HMDS-diffusion method and known- addition technique, with a mean (SE)
      difference of 0.002 (0.003) ug/mL. In conclusion, the known-addition technique
      could be a suitable alternative for the measurement of fluoride in plasma with
      microlitre-volume samples.

PMID- 30296786
TI  - Structure-Activity Relationship of the GPR55 Antagonist, CID16020046.
AB  - BACKGROUND/AIMS: CID16020046 blocks the effect of the lipid
      lysophosphatidylinositol (LPI) at its receptor, GPR55. CID16020046 and another
      antagonist, ML193, have been used to investigate GPR55-mediated effects of LPI on
      cells, tissues, and in vivo. Here we describe the structure-activity relationship
      of CID16020046. METHODS: Yeast or human cells were engineered to express GPR55 or
      control receptors. Cells were pretreated with a test agent before agonist
      challenge. Functional responses were quantified by yeast gene-reporter or calcium
      imaging. RESULTS: Three substituents around the central pyrazololactam core of
      CID16020046 are each tolerant to substitution without abolishing GPR55 activity.
      Analogues of CID16020046 with potency at GPR55 ranging >1,000-fold are described,
      including several lacking activity up to the top concentration tested. One
      analogue, compound 1 (GSK875734A), has approximately 50-fold greater potency than
      CID16020046 in an inverse agonist assay. CID16020046, ML193 and 2 further
      antagonists (ML191 and ML192) all block the effect of a surrogate agonist at
      human GPR55. ML193, CID16020046 and several other examples of the pyrazololactam
      chemotype were also shown to antagonise rat GPR55. CONCLUSION: These data confirm
      the utility of CID16020046 and ML193 as tools to investigate the physiological
      role of GPR55, and offer starting points for GPR55 antagonists with optimised
      pharmacokinetic or other properties.

PMID- 30296787
TI  - Compromised DNA Repair and Signalling in Human Granulocytes.
AB  - In previous studies, we showed impaired DNA repair in human monocytes. Here, we
      addressed the question of whether human neutrophilic granulocytes that arise from
      the same precursor as monocytes exhibit a similar phenotype and are impaired in
      repairing their DNA. We show that neutrophilic granulocytes isolated from
      peripheral blood display a lack of the same repair proteins that are missing in
      monocytes and do not show repair of their DNA when damaged by ionising radiation
      (IR) or chemical ROS. Contrary to T cells, we observed no decline in the number
      of single-strand breaks following gamma-radiation. Also, granulocytes did not
      show gammaH2AX foci formation while T cells and peripheral blood lymphocytes
      (PBL) responded. In comparison to PBL, XRCC1, PARP-1 and ligase III were not
      expressed and there was also no discernible signal for key damage response
      proteins ATM, ATR and DNA-PKCS as well as gammaH2AX in neutrophils. Time course
      and dose-response experiments confirmed the absence of H2AX phosphorylation after
      radiation treatment although an accumulation of double-strand breaks was detected
      in the neutral Comet assay. Overall, the data indicate that terminally
      differentiated neutrophilic granulocytes in the peripheral blood display strong
      downregulation of DNA repair and DNA damage response factors, which should be
      taken into account if studies with whole peripheral blood containing granulocytes
      are performed, causing a significant intra-experimental variation in the cellular
      repair capacity.

PMID- 30296788
TI  - State of the Art Enamel Remineralization Systems: The Next Frontier in Caries
      Management.
AB  - The principles of minimally invasive dentistry clearly dictate the need for
      clinically effective measures to remineralize early enamel caries lesions. While
      fluoride-mediated remineralization is the cornerstone of current caries
      management philosophies, a number of new remineralization strategies have been
      commercialized or are under development that claim to promote deeper
      remineralization of lesions, reduce the potential risks associated with high
      fluoride oral care products, and facilitate caries control over a lifetime. These
      non-fluoride remineralizing systems can be broadly categorized into biomimetic
      enamel regenerative technologies and the approaches that repair caries lesions by
      enhancing fluoride efficacy. This paper discusses the rationale for non-fluoride
      remineralization and the mechanism of action, challenges, and evidence behind
      some of the most promising advances in enamel remineralization therapies.

PMID- 30296790
TI  - Do Hospital Doctors Screen for Diabetes?
AB  - BACKGROUND: One in five hospitalized patients presents with previously undetected
      diabetes mellitus (DM). We assessed whether hospital doctors measure HbA1c in
      hospitalized patients and act consequently. METHODS: Data from patients
      hospitalized between January 2013 and December 2014 in a Swiss teaching hospital
      was collected. We assessed the frequency of HbA1c measurements and the number of
      newly detected prediabetes or DM. We also examined whether HbA1c values were
      associated with the antidiabetic drugs prescription and reporting of DM in the
      discharge letter. RESULTS: Of the 2618 patients studied, 298 (11.4%) had HbA1c
      measured, of whom 136 (45.6%) had no previous history of DM. Of the 136 patients
      without history of DM, 51 (37.5%) had prediabetic state and 23 (16.9%) had DM.
      Newly detected prediabetes or DM were reported in 5.8% (3/51) and 65.8% of cases
      (15/23), respectively. Only half of patients (11/23, 47.8%) with newly detected
      DM received antidiabetic drug treatment at discharge. Patients with newly
      detected DM (n=23) had a longer length of stay (median and interquartile range:
      16 [9-25] versus 10 [8-16] days, p=0.028) compared to patients without DM, while
      no such differences were found regarding in-hospital mortality. CONCLUSIONS:
      Hospital doctors seldom prescribe HbA1c measurement in medical hospitalized
      patients. Prescription of HbA1c measurement leads to a high detection rate (53%)
      of (pre)DM among patients unaware of their status, but management and reporting
      of these conditions at discharge could be further improved.

PMID- 30296789
TI  - Protective Effect and Mechanism of Alprostadil in Acute Respiratory Distress
      Syndrome Induced by Oleic Acid in Rats.
AB  - BACKGROUND This study investigated the role and mechanism of alprostadil in acute
      respiratory distress syndrome (ARDS) induced by oleic acid (OA) in rats. MATERIAL
      AND METHODS Sprague-Dawley rats were randomly divided into control, OA model, and
      OA + Alprostadil (2.5, 5, and 10 MUg/kg, respectively) groups. The ARDS model was
      induced by femoral vein injection of OA, and alprostadil was administrated
      immediately. Lung injury was evaluated by lung wet-dry weight ratio (W/D) and
      histological analyses. Expressions of ACE, inflammatory mediators, apoptotic
      related proteins, and proteins in the MAPKs and NF-kappaB signaling pathways were
      determined by Western blot or immunohistochemical staining. RESULTS Compared with
      the control group, the OA model group had significantly increased W/D, lung
      injury score, and collagen deposition at 3 h after OA injection. However,
      alprostadil (10 MUg/kg) treatment significantly reduced OA-induced elevation of
      these indicators. Additionally, OA-induced expression of TNF-alpha and IL-1beta
      were suppressed by alprostadil. The OA-induced activation of nuclear factor (NF)
      kappaB p65 was also reduced by alprostadil. Furthermore, we found that
      Alprostadil had an inhibitory effect on the phosphorylation of JNK, ERK1/2, and
      p38 MAPKs. Alprostadil inhibited Bax but increased Bcl-2, indicating a
      suppressive role in apoptosis. Remarkably increased expression of ACE in the OA
      model group was observed, which was decreased by alprostadil. CONCLUSIONS
      Alprostadil has a protective effect on ARDS induced by OA in rats, possibly
      through inhibiting apoptosis, suppressing the activation of MAPKs and NF-kappaB
      signaling pathways, and decreasing ACE protein expression. Therefore, the use of
      alprostadil in clinical ARDS treatment is promising.

PMID- 30296791
TI  - Morin Exerts Anti-Diabetic Effects in Human HepG2 Cells Via Down-Regulation of
      miR-29a.
AB  - Diabetes mellitus is a complex metabolic disease around the world that is
      characterized by hyperglycemia resulting from impaired insulin secretion, insulin
      action, or both. MicroRNA-29a is an important regulator of insulin signaling and
      gluconeogenesis pathways through IRS2, PI3K and PEPCK expressions which up
      regulates in Diabetes. Morin is a substantial bioflavonoid which has insulin
      mimetic effect, and interacting with nucleic acids and proteins. In this study
      HepG2 cells, were exposed to high glucose to induce diabetic condition. We have
      determined whether high glucose stimulation might promotes miR-29a expression
      level in HepG2 cells and subsequently evaluated the Morin treatment effects on
      this state. In HepG2 cells, high glucose increases miR-29a expression level and
      decreases its target genes, IRS2 and PI3K expression, and increases associated
      downstream gene in gluconeogenic pathway, PEPCK. Morin treatment down regulates
      miR-29a expression level and improves insulin signaling and glucose metabolism.
      To confirm the inhibitory effects of Morin on miR-29a, we have transfected cells
      with mimic and inhibitor-miR-29a. This study for the first time identifies that
      Morin improves diabetic condition through down regulation of the miR-29a level,
      and suggest that this new inhibitor of miR-29a may be a useful biomedicine to
      treat diabetes.

PMID- 30296793
TI  - Achieving Ideal Facial Appearance.

PMID- 30296792
TI  - Treatment of Venous Thromboembolism in Elite Athletes: A Suggested Approach to
      Individualized Anticoagulation.
AB  - Venous thromboembolism (VTE) is a leading cause of morbidity with potentially
      detrimental career consequences in elite athletes. Their unique predisposing
      factors entail a higher-than-expected VTE incidence. Anticoagulation treatment is
      challenging, especially among those athletes wishing to resume their competitive
      activities. The authors review the current VTE treatment guidelines from the
      perspective of treating elite athletes. They then provide an expert opinion
      individualized treatment approach based on the pharmacokinetic properties of
      direct oral anticoagulants that permits tailoring the drug's timing to the
      athlete's competitive endeavors. They also present low-molecular-weight heparin
      as an alternative. The proposed risk management approach allows mitigation
      against VTE recurrence, reducing the chance of major bleeding, and honoring the
      athlete's self-determination to resume their career while accepting the risks
      involved. A shared decision making with the athlete and his/her team along with
      the presence of adequate resources are key components. Ultimately, the authors
      hope this work will serve as a stepping stone to validated VTE treatment regimens
      that consider the particularities of elite athletes.

PMID- 30296794
TI  - Enhanced Contouring of Local Flaps.
AB  - Scars and flaps represent a disruption of the normal skin contour, shape, and
      texture. Successful reconstruction of facial defects with local flaps requires
      prior planning to choose the correct reconstructive method. However, thorough
      preoperative planning should include consideration of adjunctive procedures to
      improve expected postoperative results as well as potential procedures to improve
      less-than-ideal results. Approaching facial reconstruction holistically allows
      the surgeon to soberly assess his/her reconstructive results and attain
      outstanding appearance.

PMID- 30296795
TI  - Widened Dorsum: Bony and Cartilaginous Contributions.
AB  - Creation of a pleasing dorsal nasal profile in the anterior and lateral views
      requires proper analysis and planning to determine the required series of steps
      to accomplish the desired outcome. The widened nasal dorsum is a common esthetic
      complaint of the patient seeking rhinoplasty. Often patients seek an unrealistic
      result that, if accomplished, would leave them with a restricted nasal vault and
      nasal airway compromise. Nasal function must be balanced with the patient and
      surgeon's desire to narrow the nasal dorsum. Various techniques are used to
      control the width of the upper third, or bony vault, and middle third, or
      cartilaginous vault.

PMID- 30296796
TI  - Facial Scar Improvement Procedures.
AB  - Scars are a natural part of dermal healing following lacerations, incisions, or
      tissue loss. The ideal scar is narrow, flat, level with surrounding tissue, and
      difficult for the untrained eye to see due to color match and placement parallel
      to relaxed skin tension lines; however, scarring that is dyspigmented,
      hypertrophied, widened, contracted, or atrophic can be aesthetically displeasing
      or causing functional limitations. When the scar has unfavorable characteristics,
      scar revision is often indicated and the cosmetic surgeon must be knowledgeable
      of the minimally invasive as well as surgical techniques to improve aesthetics,
      reduced reoccurrence, or correct functional limitations.

PMID- 30296797
TI  - Ideal Facial Relationships and Goals.
AB  - Analysis of the face is an essential component of facial plastic surgery. In
      training, we are taught standards and ideals based on neoclassical models of
      beauty from Greek and Roman art and architecture. In practice, we encounter a
      wide range of variation in patient desires and perceptions of beauty. Our goals
      seem to be ever shifting, yet our education has provided us with a foundation
      from which to draw ideals of beauty. Plastic surgeons must synthesize classical
      ideas of beauty with patient desires, cultural nuances, and ethnic considerations
      all the while maintaining a natural appearance and result. This article gives an
      overview of classical models of facial proportions and relationships, while also
      discussing unique ethnic and cultural considerations which may influence the goal
      for the individual patient.

PMID- 30296798
TI  - Surgical and Nonsurgical Techniques in Forehead Rejuvenation.
AB  - The periorbital and forehead regions are among the most expressive parts of the
      face. A thorough understanding of the complex facial anatomy and aesthetic norms
      are essential when evaluating and treating a patient for facial brow
      rejuvenation. Not only will knowledge of the anatomy enhance facial injection and
      surgical outcomes, but will also diminish potential complications. Combining
      nonsurgical and surgical techniques, including laser and skin rejuvenation, can
      yield the most natural and effective aesthetic brow improvements.

PMID- 30296799
TI  - Gender-Related Facial Surgical Goals.
AB  - In the last several years, there has been an increasing demand for surgical
      facial feminization or masculinization to treat the gender dysphoric patient.
      However, while aesthetic ideals for facial rejuvenation are well described and
      taught, there is a relative paucity of literature on how to achieve a feminine or
      masculine morphology. It is thus becoming increasingly important for facial
      plastic surgeons to understand patient goals regarding facial feminization or
      masculinization, and to have a systematic approach for analyzing the female and
      male face.

PMID- 30296800
TI  - Correction of the Lower Face and Neck.
AB  - Rejuvenation of the lower face and neck strives to reverse signs of aging while
      optimizing the patient's natural anatomy. Common features of an aesthetically
      pleasing lower face include a well-defined and appropriately balanced mandible
      and an acute cervicomental angle. Correction of the aging lower face and neck is
      accomplished through multiple surgical interventions, performed either alone or
      in combination. Determination of appropriate procedures is based on individual
      anatomic pathology. Intimate knowledge of facial anatomy and the complexity of
      the aging process is paramount to achieve a natural and aesthetic result.
      Thorough patient evaluation and counseling should precede any intervention.
      Specifically, the surgeon should be cognizant of the patient's skeletal
      structure, soft tissue distribution, muscular anatomy, and skin quality.
      Appropriate postoperative care and management of complications are vital to
      success.

PMID- 30296801
TI  - Correction of the Crooked Nose.
AB  - Successful management of the crooked nose can be a formidable task and requires a
      systematic approach that begins with an understanding of the patients' aesthetic
      desires, expectations, and functional symptoms. Dividing the nose into thirds and
      organizing a plan to correct each region individually can simplify the
      preoperative planning. There are two broad philosophical strategies of surgical
      management: engineering (reconstructive) and artistic (camouflaging). While the
      camouflaging technique is helpful for minor asymmetries, protrusions, and
      depressions, the engineering approach is best for more extreme corrections. The
      surgeon must be skilled in both approaches as either one or a combination of the
      two may yield the best results. Once corrected, postoperative care is essential
      to obtain optimal outcomes.

PMID- 30296802
TI  - Selecting the Best Eyelid Techniques.
AB  - The periorbital region is a focal point on the face. Dermatochalasis, fat
      herniation, blepharoptosis, brow ptosis, deep tear troughs, and malar fat pad
      descent are all age-related changes that occur around the eyes, and successful
      rejuvenation involves addressing all of these changes. Restoring a youthful,
      vibrant appearance to the eyes and periorbital areas can often only be
      accomplished with a combination of surgical and nonsurgical interventions. Facial
      plastic surgeons should have a comprehensive knowledge of all of these options
      and their applications to ensure good patient outcomes and satisfaction.

PMID- 30296803
TI  - Rejuvenation of the Midface.
AB  - In this article, the interested reader will learn when and how to apply different
      techniques on their patients, with the goal of safe, effective, natural looking,
      and long-lasting midface rejuvenation.

PMID- 30296804
TI  - A Natural Phenolic Compound Quercetin Showed the Usefulness by Targeting
      Inflammatory, Oxidative Stress Markers and Augment 5-HT Levels in One of the
      Animal Models of Depression in Mice.
AB  - AIM: In the present study quercetin was studied for its role in inflammation,
      oxidative stress markers and 5-HT levels in unpredictable chronic mild stress
      (UCMS) animal model of depression. MATERIALS AND METHODS: The mice were
      randomized into different groups trained for UCMS protocol followed by different
      drug treatments. Treatments were started after 2 weeks from the start of UCMS
      protocol and continued up to 6 weeks. The behavioral tests such as modified
      forced swimming (MFST), tail suspension (TST) and open field tests were performed
      on week 6, at least 24 h after the last drug treatment. Behavioral tests were
      preceded following animal sacrifice for biochemical estimations. RESULTS: A
      significant decrease in swimming, climbing times and increase in immobility time
      in MFST and TST was observed in UCMS group. Administration of quercetin (25 mg/kg
      per orally (p.o) reversed these times in MFST and TST. A decrease in no. of field
      crossing, time spent in centre and no. of rearing were observed in UCMS group.
      Quercetin reduced these observations in open field test. There was a decrease in
      superoxide dismutase (SOD), glutathione (GSH), catalase and 5 HT levels in the
      brain tissue. Quercetin treatment significantly augmented SOD, GSH, catalase and
      5 HT levels. Glutamate, TNF-alpha and IL-6 levels were increased in UCMS group
      while quercetin decreased these cytokines. CONCLUSION: Quercetin resulted
      antidepressant-like effect by its antioxidant, anti-inflammatory activities,
      reduced excitotoxicity and augmented 5 HT levels. This pointed out the usefulness
      of this phenolic compound as adjuvent drug along with other antidepressant drugs.

PMID- 30296805
TI  - Effect of Canagliflozin on Heart Function Involving Ketone Bodies in Patients
      with Type 2 Diabetes.
AB  - This report describes the effect of administration (n=3) or withdrawal (n=2) of
      canagliflozin, a sodium-glucose co-transporters 2 (SGLT-2) inhibitor, on cardiac
      function in relation to ketone bodies. Three cases received and two cases
      discontinued canagliflozin. Changes of heart function with ultrasonography (EF:
      ejection fraction and %FS: functional shortening) and cardiometabolic parameters
      including ketone bodies (acetoacetate/beta-hydroxybutylate) were compared at 3
      months. 69, 68 and 60 years old male patients A, B and C, respectively with
      moderately decreased heart function received canagliflozin 100 mg/day. EF, %FS
      and acetoacetate/beta-hydroxybutylate levels increased. 60 and 59 years old
      female patients D and E with normal and borderline heart function, respectively
      discontinued canagliflozin 50 mg/day. EF, %FS and acetoacetate/beta
      hydroxybutylate levels decreased. Taken together, these results suggest that
      concomitant changes between ketone bodies and heart function were observed with
      or without canagliflzoin. This drug might have effects on cardiac function
      through modulating ketone bodies.

PMID- 30296806
TI  - Review of Clinical Pharmacokinetics of Avibactam, A Newly Approved non-beta
      lactam beta-lactamase Inhibitor Drug, In Combination Use With Ceftazidime.
AB  - Avibactam, a potent non-beta lactam beta-lactamase inhibitor, was recently
      approved in the USA for combination use with ceftazidime, a cephalosporin
      antibiotic drug. The addition of avibactam potentiates the antimicrobial drug
      ceftazidime, which otherwise would have been susceptible to beta-lactamases
      produced by variety of Gram negative pathogens. The focus of this review was to
      provide clinical pharmacokinetic data of avibactam to cover absorption,
      distribution, metabolism, and excretion aspects including any potential for
      avibactam to show drug-drug interactions in the clinic. Based on the review of
      the data, the pharmacokinetics of avibactam was generally stationary in the
      studied dosing regimen. The elimination half-life (approximately 1.4- 3.2 h) and
      volume of distribution at steady state (15.4-26.3 L) were found similar across
      the studies and therefore, provided the complementary pharmacokinetic attributes
      for combination use with ceftazidime. Renal excretion was the major pathway for
      the clearance of avibactam. In summary, any degree of renal dysfunction is
      expected to alter the pharmacokinetics of avibactam - this consideration should
      be factored in dosage adjustments while dosing in patients with renal impairment.
      Concomitant drugs that may influence renal mechanism of elimination of avibactam
      should be avoided and/or monitored for any impact on the pharmacokinetics of
      avibactam.

PMID- 30296807
TI  - [Extramedullary Plasmacytoma].

PMID- 30296808
TI  - Analysis of Machine Learning Algorithms for Diagnosis of Diffuse Lung Diseases.
AB  - BACKGROUND:  Diffuse lung diseases (DLDs) are a diverse group of pulmonary
      disorders, characterized by inflammation of lung tissue, which may lead to
      permanent loss of the ability to breathe and death. Distinguishing among these
      diseases is challenging to physicians due their wide variety and unknown causes.
      Computer-aided diagnosis (CAD) is a useful approach to improve diagnostic
      accuracy, by combining information provided by experts with Machine Learning (ML)
      methods. OBJECTIVES:  Exploring the potential of dimensionality reduction
      combined with ML methods for diagnosis of DLDs; improving the classification
      accuracy over state-of-the-art methods. METHODS:  A data set composed of 3252
      regions of interest (ROIs) was used, from which 28 features were extracted per
      ROI. We used Principal Component Analysis, Linear Discriminant Analysis, and
      Stepwise Selection - Forward, Backward, and Forward-Backward to reduce feature
      dimensionality. The feature subsets obtained were used as input to the following
      ML methods: Support Vector Machine, Gaussian Mixture Model, k-Nearest Neighbor,
      and Deep Feedforward Neural Network. We also applied a Deep Convolutional Neural
      Network directly to the ROIs. RESULTS:  We achieved the maximum reduction from 28
      to 5 dimensions using LDA. The best classification results were obtained by DFNN,
      with 99.60% of overall accuracy. CONCLUSIONS:  This work contributes to the
      analysis and selection of features that can efficiently characterize the DLDs
      studied.

PMID- 30296809
TI  - Prehospital Telemedical Emergency Management of Severely Injured Trauma Patients.
AB  - BACKGROUND:  Trauma is a global burden. Emergency medical services (EMS) provide
      care for individuals who have serious injuries or suffered a major trauma.
      OBJECTIVE:  This paper provides a comprehensive overview of telemedicine
      applications in prehospital trauma care. METHODS:  We conducted a systematic
      review according to PRISMA guidelines. We identified articles by electronic
      database search (PubMed, EMBASE, the Cochrane Library, CINAHL, SpringerLink,
      LIVIVO, DARE, IEEE Xplore, Google Scholar and ScienceDirect) using keywords
      related to prehospital settings, ambulance, telemedicine and trauma. Search terms
      and inclusion criteria were specified a priori by the PICOS template and revised
      throughout a configurative approach iteratively, to outline the complexity and
      variety of different telemedical concepts. RESULTS:  A final sample of 15 records
      was systematically selected. Most interventions were piloted and/or evaluated in
      Germany for trauma victims in prehospital settings. Six studies were simulated
      scenarios. Telemedical assistance (TMA) via real-time telemetry systems (RTS),
      enabling video and audio conferencing between EMS by tele-emergency physicians
      (TEP) were associated with a higher treatment quality and a shorter time-to
      treatment in invasive procedures. By initiating in-hospital preparations based on
      telemedical prehospital notification (TPN), loss of information during the
      clinical handover was reduced and in-hospital protocols were activated with high
      accuracy. Remotely guided ultrasound (Tele-Ultrasound) by TEP showed an overall
      high diagnostic accuracy in simulations. Technical solutions were reliable,
      seemed practical and auspicious. CONCLUSION:  The review indicates that TMA and
      TPN are accompanying telemedical concepts in out-of-hospital trauma care. Well
      designed populated studies are needed to fully assess the effect of telemedicine
      in acute trauma care. Therefore, evidence regarding the effectiveness of
      telemedicine in prehospital setting for trauma patients is still limited.

PMID- 30296810
TI  - [Correction: Breast reconstruction with the free TRAM or DIEP flap - What is the
      current standard? - Consensus Statement of the German Speaking Working Group for
      Microsurgery of the Peripheral Nerves and Vessels].

PMID- 30296811
TI  - Peroral endoscopic myotomy (POEM) is effective in treatment of noncardiac chest
      pain caused by hypercontractile esophageal motility disorders: results of the
      POEM-HYPE-Study.
AB  - BACKGROUND: Noncardiac chest pain (NCCP) is recurrent angina pectoris-like pain
      without evidence of coronary heart disease in conventional diagnostic evaluation.
      In gastroenterology, managing of patients with NCCP is ambiguous to detect
      gastroesophageal reflux and hypercontractile esophageal motility disorders.
      Recently, peroral endoscopic myotomy (POEM) was established as treatment option
      in achalasia. However, limited data exist on the effectivity of POEM in NCCP with
      hypercontractile esophageal motility disorders. MATERIAL AND METHODS: In this
      prospective study (POEM-HYPE), we evaluated 14 patients with NCCP and
      hypercontractile esophageal motility disorders (type III achalasia, n = 7;
      hypercontractile esophagus, n = 6; distal esophageal spasm, n = 1). All patients
      underwent standardized diagnostic work-up including esophagogastroduodenoscopy
      with esophageal biopsies, high-resolution esophageal manometry, and combined
      intraluminal impedance and pH testing before and 3 weeks after POEM. A
      standardized symptom questionnaire was disposed before POEM, 3 weeks after, and
      every 6 months after the POEM. RESULTS: After POEM, 12 patients showed
      significant symptom relief (pre-Eckardt score: 7.78 +/- 1.47, 3 weeks post: 1.64
      +/- 1.44, 6 months: 2.0 +/- 1.84 and 1.86 +/- 1.89 after 15.0 +/- 10.0 months
      post-intervention). High-resolution manometry showed significant reduction in
      integrated relaxation pressure (pre-POEM: 24.74 +/- 18.9 mm Hg, post-POEM: 13.8
      +/- 16.5 mm Hg) and distal contractile integral (pre-POEM: 2880 +/- 3700
      mmHg*s*cm, post-POEM: 1109 +/- 1042 mmHg*s*cm). One lesion of the submucosal
      tunnel occurred as a moderate adverse event and was handled endoscopically. The
      long-term clinical success rate was 85.7 %. No severe gastroesophageal reflux
      occurred after interventions. Two patients required secondary therapy with
      injection of botulinum toxin in the tubular esophagus and balloon dilation.
      CONCLUSION: The results suggest that POEM is an effective and safe therapeutic
      option for patients with NCCP and hypercontractile esophageal motility disorders.

PMID- 30296812
TI  - Surgical therapy of chronic pancreatitis: clinical results and health-related
      quality of life.
AB  - INTRODUCTION:  There are several well-established surgical procedures for the
      treatment of chronic pancreatitis (CP). The present study seeks to evaluate the
      perioperative and long-term outcome of these procedures. METHODS:  All patients
      who had undergone pancreaticoduodenectomy (PD), duodenum-preserving pancreatic
      head resection (DPPHR), and distal pancreatectomy (DP) for CP were
      retrospectively analyzed with regards to the perioperative outcome and long-term
      survival. Health-related quality of life (HRQoL) was assessed using the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire.
      RESULTS:  There were 145 patients available for analysis. Major complications
      (grade IIIb-V) occurred in 19 %, in-hospital mortality was 4.2 %, and 90-day
      mortality was 3 % with no differences between the different resection groups (all
      p > 0.05). Ten-year survival was 58 % and was highest in the DP group (100 %) but
      without statistical significance (p = 0.72). The response rate of the HRQoL
      assessment was 45 % (65 of 145). There was a significant improvement with regards
      to pain and HRQoL of all resection groups compared to the preoperative group (all
      p < 0.05). With respect to HRQoL and pain relief, the PD, DPPHR, and DP did not
      differ significantly. DISCUSSION:  Surgical therapy of CP can be performed
      safely. The 3 different types of resection performed equally with regards to
      complications and HRQoL.

PMID- 30296813
TI  - Isolated Tricuspid Valvectomy: A Series of cases with Intravenous Drug Abuse
      Associated Tricuspid Valve Endocarditis.
AB  - INTRODUCTION:  Surgical management for tricuspid valve (TV) endocarditis is
      usually TV repair or replacement. When repair is not feasible, and concerns for
      patient recidivism preclude TV replacement, tricuspid valvectomy without
      replacement is an option to alleviate symptoms and allow time for addiction
      management. METHODS:  We reviewed our institution's experience with isolated
      tricuspid valvectomy for cases of intravenous drug use (IVDU)-associated
      endocarditis (n = 7) from 2009 to 2017. RESULTS:  The decision for tricuspid
      valvectomy was based on each patient's comorbid condition and realization of
      active IVDU. This intervention resulted in 100% perioperative and mid-term
      survival with a mean follow-up of 25.4 months. One patient required a valve
      replacement in the long term only after appropriate substance abuse management
      was completed. CONCLUSION:  Cardiac surgeons increasingly encounter patients with
      active endocarditis who suffer from IVDU addiction. Drug addiction increases the
      risk for recurrent endocarditis and requires an effective management plan.
      Multidisciplinary endocarditis care teams may play a pivotal role in improving
      outcomes by better addressing addiction treatment.

PMID- 30296814
TI  - New Device for the Treatment of Functional Ischemic Mitral Regurgitation: Proof
      of Concept in an In Vitro Model.
AB  - BACKGROUND:  Optimal surgical treatment of functional ischemic mitral
      regurgitation (FIMR) is still controversy. Due to the underlying pathophysiology,
      stand-alone ring annuloplasty is assumed with a high recurrence rate of mitral
      regurgitation, thus additional subvalvular repair techniques might improve the
      results. This in vitro study introduces a new device for subvalvular mitral valve
      repair. METHODS:  We developed a new device for subvalvular mitral valve repair,
      consisting of two frames for papillary muscle (PM) attachment, which are
      connected with two holding bars serving for fixation of the device on an
      annuloplasty ring. In the first experimental run, porcine mitral valves including
      the chordae tendineae and PMs were fixated on a holding device, consisting of a
      holding ring simulating mitral annulus dilation and height-adjustable frames for
      PM attachment simulating leaflet tethering. In vitro regurgitant volume was
      determined in a pulse duplicator. Afterward, the frames for PM attachment were
      replaced by our newly developed device and the measurements were repeated.
      RESULTS:  In the model simulating FIMR, the regurgitant volume was 44.3 +/- 12.38
      mL/stroke. After subvalvular reconstruction with our new device, the regurgitant
      volume was significantly reduced to 33.1 +/- 11.68 mL/stroke (p = 0.009).
      CONCLUSION:  In this specific in vitro model, our new device for subvalvular
      mitral valve reconstruction led to a significant reduction of the regurgitant
      volume, thus representing a promising technique to potentially improve the
      results of mitral reconstruction in ischemic functional mitral valve
      regurgitation. Additional studies are required to further investigate and improve
      our device.

PMID- 30296815
TI  - Association of Platelet-to-Lymphocyte Ratio and Neutrophil-to-Lymphocyte Ratio
      with the Risk of Thromboembolism and Mortality in Patients with Cancer.
AB  - Patients with cancer are at risk of developing venous and arterial
      thromboembolism (VTE and ATE). Elevated platelet-to-lymphocyte (PLR) and
      neutrophil-to-lymphocyte ratios (NLR) have been suggested as potential biomarkers
      for cancer-associated chronic inflammation, VTE and mortality. We investigated
      the association between PLR and NLR with VTE, ATE and mortality in patients with
      cancer. Within a prospective cohort study, we followed-up patients with newly
      diagnosed or progressing cancer for objectively confirmed, symptomatic VTE, ATE
      and death. Fine and Gray competing-risk regression was used to model the risk of
      VTE and ATE. Overall survival was analysed with Kaplan-Meier estimators. From
      2003 to 2013, 1,469 patients with solid cancer (median age: 61 years; 47.3%
      female) were recruited and followed for 2 years. Overall, 128 (8.7%) patients
      developed VTE, 41 (2.8%) ATE and 643 (43.8%) patients died. The sub-distribution
      hazard ratios (SHRs) for VTE per doubling of PLR and NLR were 1.0 (95% confidence
      interval [CI]: 0.8-1.3, p = 0.899) and 1.2 (1.0-1.4, p = 0.059), respectively.
      For ATE, the SHR per doubling of PLR and NLR were 1.0 (0.7-1.5, p = 0.940) and
      1.2 (0.9-1.6, p = 0.191), respectively. A higher PLR (hazard ratio [HR] per
      doubling = 1.5, 1.4-1.7, p < 0.001) and a higher NLR (HR per doubling = 1.5, 1.4
      1.7, p < 0.001) were associated with an increased risk of mortality after
      adjusting for age, sex and cancer stage. There was no statistically significant
      association between NLR and VTE occurrence in patients with cancer. Neither PLR
      nor NLR were associated with the risk of ATE. Both elevated PLR and NLR were
      independently associated with a twofold increased risk of mortality.

PMID- 30296816
TI  - Successful Pregnancy under Fibrinogen Substitution with Heparin and Aspirin in a
      Woman with Dysfibrinogenemia Revealed by Placental Abruption.

PMID- 30296817
TI  - Venous Thromboembolism in Women Undergoing Assisted Reproductive Technologies:
      Data from the RIETE Registry.
AB  - Venous thromboembolism (VTE) during or after assisted reproductive technologies
      (ART) is predicted to rise due to the increased number of women undergoing this
      technique. We present data collected in the RIETE registry up to October 2016.
      Overall, 41 (0.6%) out of 6,718 women of childbearing age with VTE had an ART
      related event. Most of them underwent autologous ART cycles; 23 had isolated deep
      vein thrombosis (DVT) (56.1%), 12 isolated pulmonary embolism (PE) (29.3%) and 6
      simultaneous occurrence of both the events (14.6%). VTE occurred in 20 successful
      and 21 unsuccessful (i.e. not resulting in a clinical pregnancy) ART cycles. No
      recurrence was observed at 90 days. Logistic regression showed that isolated PE
      was significantly more frequent than DVT alone or combined with PE in
      unsuccessful in vitro fertilization (IVF) (odds ratio [OR]: 4.13, 95% confidence
      interval [CI]: 1.4-12.4), as well as in contraceptive users (OR: 2.96, 95% CI:
      1.95-4.5) and in puerperium (OR: 1.96, 95% CI: 1.16-3.3). After grouping isolated
      PE and DVT + PE, we found that PE was significantly more frequent in women with
      unsuccessful IVF and higher body mass index (OR: 5.0, 95% CI: 1.2-20.7 and OR:
      1.0, 95%CI: 1.0-1.1, respectively). These data document a higher risk of PE in
      unsuccessful cycles than in successful ones. The risk is higher than that
      observed during pregnancy, puerperium and contraception.

PMID- 30296818
TI  - Prospective Study of Endogenous Hormones and Incidence of Venous Thromboembolism:
      The Atherosclerosis Risk in Communities Study.
AB  - Exogenous hormone treatments in women (oral contraceptives and hormone
      replacement therapy [HRT]) are established risk factors for venous
      thromboembolism (VTE), but less is known about associations between plasma levels
      of endogenous hormones and VTE risk. We examined the association of baseline
      dehydroepiandrosterone sulphate (DHEAS), testosterone and sex hormone-binding
      globulin (SHBG) with risk of future VTE in men and post-menopausal women in the
      Atherosclerosis Risk in Communities Study. Testosterone, DHEAS and SHBG were
      measured in plasma samples collected in 1996 to 1998. Cox proportional hazards
      models were used to estimate hazard ratios for incident VTE adjusting for age,
      race/ethnicity, body mass index, height, smoking, estimated glomerular filtration
      rate and C-reactive protein. All analyses were stratified by sex and by current
      HRT use in women. Among 3,051 non-HRT-using women, 1,414 HRT-using women and
      3,925 men at risk at baseline, 184, 62 and 206 experienced incident VTE after a
      median follow-up of 17.6 years. Plasma hormones were not associated with
      incidence of VTE among men and non-HRT-using women, although lower plasma DHEAS,
      when modelled using quartiles or restricted cubic splines, was associated with
      higher risk of VTE among HRT-using women. This study does not support the
      existence of an important association between plasma concentrations of endogenous
      testosterone, DHEAS or SHBG with risk of VTE in middle-aged to older men or post
      menopausal women not using HRT.

PMID- 30296819
TI  - Experience of racism and associations with unmet need and healthcare
      satisfaction: the 2011/12 adult New Zealand Health Survey.
AB  - OBJECTIVE: Racism may affect health through differential access to, and quality
      of, healthcare. This study examined associations between experience of racism and
      unmet need and satisfaction with healthcare. METHODS: Cross-sectional analysis of
      the 2011/12 adult New Zealand Health Survey (n=12,596) was undertaken. Logistic
      regression was used to examine associations between experience of racism (by a
      health professional and other experiences of racism [ever]) and unmet need for a
      general practitioner and satisfaction with a usual medical centre in the past
      year. RESULTS: Experience of racism by a health professional and other forms of
      racism were higher among Maori, Pacific and Asian groups compared to
      European/Other. Both racism measures were associated with higher unmet need
      (health professional racism adjusted OR 3.52, 95%CI 2.42-5.11; other racism OR
      2.21, 95%CI 1.78-2.75) and lower satisfaction with a usual medical centre (health
      professional racism adjusted OR 0.25, 95%CI 0.15-0.34; other racism OR 0.60,
      95%CI 0.45-0.79). CONCLUSIONS: Racism may act as a barrier to, and influence the
      quality of, healthcare. Implications for public health: Addressing racism as a
      public health issue and major driver of inequities in healthcare and health
      outcomes is required within the health sector and wider society.

PMID- 30296820
TI  - Carbon pricing of food in Australia: an analysis of the health, environmental and
      public finance impacts.
AB  - OBJECTIVE: To estimate the impact of integrating the price of greenhouse gas
      emissions into the price of food commodities on dietary and weight-related risk
      factors and associated disease burden in Australia, as well as on national
      emissions reductions and public revenues. METHODS: We used country-specific data
      for Australia to build a coupled modelling framework that includes economic,
      environmental and health analyses. Data sources included the 2011-12 Australian
      food and nutrition survey, meta-analysis of food-related lifecycle emissions, and
      price and income elasticities. Consumption-related changes in disease burden were
      calculated using a comparative risk assessment framework with 11 disease states
      and seven diet and weight-related risk factors. RESULTS: Including a price of $23
      per tonne of carbon dioxide equivalent (tCO2-eq) - the starting price of the
      former Australian carbon pricing mechanism - into the price of food commodities
      in our model simulations led to 49,500 avoided disability-adjusted life years
      (DALYs) (95% confidence interval [CI] 43,200-55,200). Food-related greenhouse gas
      emissions were reduced by 6% (2.3 MtCO2-eq), and greenhouse gas tax revenues
      amounted to $866 million. CONCLUSION: Incorporating the price of food-related
      greenhouse gas emissions into the price of food commodities in Australia could be
      beneficial for population health, while generating public finance revenues and
      supporting Australia's emission-reduction commitment. Implications for public
      health: Climate policies that integrate the price of greenhouse gas emissions
      into the price of food commodities in Australia are compatible with public health
      objectives to reduce diet-related disease mortality.

PMID- 30296821
TI  - Where children play most: physical activity levels of school children across four
      settings and policy implications.
AB  - OBJECTIVE: This study examined physical activity levels among 2,296 Queensland
      school children in the school, club sport, active transport and free time
      settings. Childhood physical activity contributes to musculoskeletal strength,
      psychosocial benefits and cardiovascular health. METHODS: Data were collected
      from parents by computer-assisted telephone interview on an annual preventive
      health monitoring survey conducted by the Queensland Government. RESULTS: Parents
      reported that children achieved the largest proportions of their physical
      activity in school (33%) or their free time (42%). Moderate participation levels
      were reported for active transport and organised sport and these activities
      contributed lower proportions to total physical activity (10% and 15%,
      respectively). After adjusting for age and sex, living in a family with higher
      levels of activity and with a parent that knows physical activity guidelines was
      associated with higher activity levels. Implications for public health:
      Increasing physical activity in settings where less active children are already
      participating, specifically in school settings and during free time, may have
      more immediate benefits than encouraging children to be active in new settings.
      Many children achieve seven or more hours of physical activity weekly but do not
      meet the physical activity guideline criterion of 60 minutes of physical activity
      daily; consequently, quantifying physical activity solely against the guidelines
      may underestimate children's physical activity.

PMID- 30296822
TI  - Collaborative population health planning between Australian primary health care
      organisations and local government: lost opportunity.
AB  - OBJECTIVE: To examine the strength and extent of collaborations between primary
      health care organisations and local government in population health planning.
      METHODS: Methods included: a) online surveys with Medicare Locals (n=210) and
      Primary Health Networks (n=66), comparing the two using two-level mixed models;
      b) interviews with Medicare Local (n=50) and Primary Health Network (n=55)
      executives; c) interviews with members of local government associations and
      Primary Health Network board members with local government experience (n=7); and
      d) review of 54 Medicare Local and 31 Primary Health Network publicly available
      annual reports. RESULTS: Despite partnership being a policy objective for
      Medicare Locals/ Primary Health Networks, they reported limited time and
      financial support for collaboration with local government. Organisational
      capacity and resources, supportive governance and public health legislation
      mandating a role for local governments were critical to collaborative planning.
      CONCLUSIONS: Local government has the potential to tackle social factors
      affecting health; therefore, their inclusion in population health planning is
      valuable. Legislative mandates would help to achieve this, and PHNs require a
      stronger Federal Government mandate backed by sufficient resources and a
      governance structure that supports collaboration. Implications for public health:
      Improving primary health care and local government collaboration has great
      potential to improve the quality of health planning and action on social
      determinants, thus advancing population health and health equity.

PMID- 30296823
TI  - How much free sugar do Australians consume? Findings from a national survey.
AB  - OBJECTIVE: To identify the characteristics of Australian adults exceeding the
      World Health Organization's free sugar (FS) intake recommendations of <10% and
      compare the sources of FS among those exceeding (high FS consumers) and complying
      (low FS consumers) with the recommendations. METHOD: Nationally weighted data
      from the Australian National Nutrition and Physical Activity Survey 2011-12 was
      used to describe the proportions of FS consumption and sources of FS among adults
      aged >=18 years (n=9,435) across demographic, socioeconomic and health
      behavioural subgroups. Six categories of food groups likely to contain FS were
      generated and analysed. RESULTS: Almost half of all adults (47%) were high FS
      consumers. More than one-third of adults in each demographic, socioeconomic and
      health behaviour subgroup were high FS consumers. Of the food groups containing
      FS, beverages contributed the most FS (37%), particularly for young adults (48%).
      High FS consumers obtained twice as much FS from beverages (42%) than low FS
      consumers (21%). A reverse age gradient was observed for the FS sourced from
      beverages. CONCLUSIONS: Almost half the Australians surveyed exceeded the FS
      intake recommendations. Sugary beverages were the largest source of FS, with
      young adults being the highest consumers. Implications for public health: Whole
      population strategies targeting beverages could possibly reduce Australia's high
      sugar intake.

PMID- 30296825
TI  - Phenylnitrene Radical Cation Rearrangements.
AB  - The electronic structure and the rearrangements of the phenylnitrene radical
      cation C6H5N.+ 2.+ have been investigated at DFT and CASPT2(7,9) levels of
      theory. The 2B2 state has the lowest energy of five identified electronic states,
      and it can undergo ring expansion to the 1-azacycloheptetetraene radical cation
      4.+ with an activation energy of ca. 28 kcal/mol. Ring opening and recyclization
      provide a route to 5-cyanocyclopentadiene radical cation 8.+, which may undergo
      facile 1,5-hydrogen shifts. The 2-, 3-, and 4-pyridylcarbene radical cations
      31.+, 35.+ , and 39.+ interconvert with the phenylnitrene radical cation via
      azacycloheptatetraenes with activation barriers <35 kcal/mol. The carbene-carbene
      and carbene-nitrene rearrangements, ring expansions, ring contractions, ring
      openings (e.g., to cyanopentadienylidene 28.+), and cyclizations taking place in
      all these radical cations are completely analogous to the thermal and
      photochemical rearrangements.

PMID- 30296824
TI  - A Thermodynamic Model for Multivalency in 14-3-3 Protein-Protein Interactions.
AB  - Protein-protein interactions (PPIs) are at the core of molecular control over
      cellular function. Multivalency in PPI formation, such as via proteins with
      multiple binding sites and different valencies, requires fundamental
      understanding to address correlated challenges in pathologies and drug
      development. Thermodynamic binding models are needed to provide frameworks for
      describing multivalent PPIs. We established a model based on ditopic host-guest
      systems featuring the effective molarity, a hallmark property of multivalency, as
      a prime parameter governing the intramolecular binding in divalent interactions.
      By way of illustration, we study the interaction of the bivalent 14-3-3 protein
      scaffold with both the nonavalent CFTR and the hexavalent LRRK2 proteins,
      determining the underlying thermodynamics and providing insights into the role of
      individual sites in the context of the multivalent platform. Fitting of binding
      data reveals enthalpy-entropy correlation in both systems. Simulations of
      speciations for the entire phosphorylated protein domains reveal that the CFTR
      protein preferably binds to 14-3-3 by combinations including the strongest
      binding site pS768, but that other binding sites take over when this site is
      eliminated, leading to only a minor decrease in total affinity for 14-3-3. For
      LRRK2, two binding sites dominate the complex formation with 14-3-3, but the
      distantly located pS1444 site also plays a role in complex formation.
      Thermodynamic modeling of these multivalent PPIs allowed analyzing and predicting
      the effects of individual sites regarding their modulation via, for example,
      (de)phosphorylation or small-molecule targeting. The results specifically bring
      forward the potential of PPI stabilization, as an entry for drug discovery for
      multivalent PPIs.

PMID- 30296826
TI  - Fluorescent Gold Nanocluster-Based Sensor Array for Nitrophenol Isomer
      Discrimination via an Integration of Host-Guest Interaction and Inner Filter
      Effect.
AB  - The rapid discrimination of nitrophenol isomers has been a long-standing
      challenge because of the tiny structural differences among the isomers. In this
      study, a fluorescent sensor array based on three different-color emitting gold
      nanoclusters (Au NCs) that were functionalized with three different ligands and a
      cocapping ligand beta-cyclodextrin (beta-CD) has been constructed for the facile
      discrimination of three nitrophenol isomers via the linear discriminant analysis
      of isomer-induced fluorescence quenching patterns. The fluorescence quenching
      occurs in two steps: first, beta-CDs adsorb nitrophenol isomers onto the surface
      of Au NCs via a host-guest interaction; second, each nitrophenol isomer quenches
      the fluorescence of a specific type of Au NCs through diverse inner filter
      effect. The different binding affinities between beta-CD and each nitrophenol
      isomer, as well as the distinct quenching efficiencies of the isomers on the
      fluorescence of each Au NCs, enable an excellent discrimination of the three
      isomers at a concentration of 5 MUM, when linear discriminant and hierarchical
      cluster analyses were smartly combined. In addition, even a mixture of two
      isomers could be distinguished with the proposed sensor array. The practicability
      of this developed sensor array is validated by a high accuracy (98.0%)
      examination of 51 unknown samples containing a single isomer or a mixture of two
      isomers.

PMID- 30296827
TI  - Coating 3D Printed Polycaprolactone Scaffolds with Nanocellulose Promotes Growth
      and Differentiation of Mesenchymal Stem Cells.
AB  - 3D printed polycaprolactone (PCL) has potential as a scaffold for bone tissue
      engineering, but the hydrophobic surface may hinder optimal cell responses. The
      surface properties can be improved by coating the scaffold with cellulose
      nanofibrils material (CNF), a multiscale hydrophilic biocompatible biomaterial
      derived from wood. In this study, human bone marrow-derived mesenchymal stem
      cells were cultured on tissue culture plates (TCP) and 3D printed PCL scaffolds
      coated with CNF. Cellular responses to the surfaces (viability, attachment,
      proliferation, and osteogenic differentiation) were documented. CNF significantly
      enhanced the hydrophilic properties of PCL scaffolds and promoted protein
      adsorption. Live/dead staining and lactate dehydrogenase release assays confirmed
      that CNF did not inhibit cellular viability. The CNF between the 3D printed PCL
      strands and pores acted as a hydrophilic barrier, enhancing cell seeding
      efficiency, and proliferation. CNF supported the formation of a well-organized
      actin cytoskeleton and cellular production of vinculin protein on the surfaces of
      TCP and PCL scaffolds. Moreover, CNF-coated surfaces enhanced not only alkaline
      phosphatase activity, but also collagen Type-I and mineral formation. It is
      concluded that CNF coating enhances cell attachment, proliferation, and
      osteogenic differentiation and has the potential to improve the performance of 3D
      printed PCL scaffolds for bone tissue engineering.

PMID- 30296828
TI  - Molecular Bottlebrushes as Novel Materials.
AB  - Molecular bottlebrushes are building blocks for the design of unique polymeric
      materials whose physical properties are fundamentally governed by their densely
      grafted structures. Recent developments in the area of reversible deactivation
      radical polymerization enabled facile and effective control over multiple
      molecular parameters. Owing to large molecular size, anisotropic conformation,
      and reduced chain entanglement, molecular bottlebrushes have empowered various
      applications that are challenging to achieve with linear polymers. In this
      Review, we focus on determining correlations between brushlike architectures and
      materials properties.

PMID- 30296829
TI  - Zwitterionic Osmolytes Resurrect Electrostatic Interactions Screened by Salt.
AB  - Many cells synthesize significant quantities of zwitterionic osmolytes to cope
      with the osmotic stress induced by excess salt. In addition to their primary role
      in balancing osmotic pressure, these osmolytes also help stabilize protein
      structure and restore enzymatic activity compromised by high ionic strength. This
      osmoprotective effect has been studied extensively, but its electrostatic aspects
      have somehow escaped the mainstream. Here, we report that, despite their overall
      neutrality, zwitterions may dramatically affect electrostatic interactions in
      saline solutions of biological relevance. Using atomic force microscopy, we study
      the combined effect of osmolytes and salts on electrostatic interactions between
      two negatively charged silica surfaces in mixtures of five salts (NaCl, KCl,
      CsCl, MgCl2, and CaCl2) and five zwitterionic osmolytes (betaine, proline,
      trimethylamine N-oxide, glycine, and sarcosine) as a function of solutes
      concentration and pH. All osmolytes are found to counteract the screening effect
      of salt on electrostatic repulsion, albeit to a different extent. They do so by
      both increasing the screening length shortened by added salts and by desorbing
      bound protons and cations, hence enhancing the negative surface charge. Both
      effects are traced to the osmolytes' higher molecular polarizability compared
      with water. In addition to this direct effect on the solution's dielectric
      constant, we identify an osmolytic Hofmeister effect with the more hydrophobic
      osmolytes more efficiently desorbing weakly hydrated cations from weakly hydrated
      silica and the less hydrophobic osmolytes better desorbing strongly hydrated
      cations from strongly hydrated silica. The combined results shed light on Coulomb
      interactions in a more realistic model of the cytosol, a relatively unexplored
      territory.

PMID- 30296830
TI  - Ionization of Ammonia Nanoices with Adsorbed Methanol Molecules.
AB  - Large ammonia clusters represent a model system of ices that are omnipresent
      throughout the space. The interaction of ammonia ices with other hydrogen-boding
      molecules such as methanol or water and their behavior upon an ionization are
      thus relevant in the astrochemical context. In this study, ammonia clusters (NH3)
      N with the mean size N ~ 230 were prepared in molecular beams and passed through
      a pickup cell in which methanol molecules were adsorbed. At the highest exploited
      pickup pressures, the average composition of (NH3) N(CH3OH) M clusters was
      estimated to be N: M ~ 210:10. On the other hand, the electron ionization of
      these clusters yielded about 75% of methanol-containing fragments (NH3) n(CH3OH)
      mH+ compared to 25% contribution of pure ammonia (NH3) nH+ ions. On the basis of
      this substantial disproportion, we propose the following ionization mechanism:
      The prevailing ammonia is ionized in most cases, resulting in NH4+ core solvated
      most likely with four ammonia molecules, yielding the well-known "magic number"
      structure (NH3)4NH4+. The methanol molecules exhibit a strong propensity for
      sticking to the fragment ion. We have also considered mechanisms of intracluster
      reactions. In most cases, proton transfer between ammonia units take place. The
      theoretical calculations suggested the proton transfer either from the methyl
      group or from the hydroxyl group of the ionized methanol molecule to ammonia to
      be the energetically open channels. However, the experiments with selectively
      deuterated methanols did not show any evidence for the D+ transfer from the CD3
      group. The proton transfer from the hydroxyl group could not be excluded entirely
      or confirmed unambiguously by the experiment.

PMID- 30296831
TI  - One-Pot Double [3 + 2] Cycloadditions for Diastereoselective Synthesis of
      Pyrrolidine-Based Polycyclic Systems.
AB  - Sequential inter- and intramolecular [3 + 2] cycloadditions of azomethine ylides
      are developed for the one-pot and diastereoselective synthesis of highly
      condensed heterocyclic systems containing pyrrolidine and up to seven
      stereocenters. It has high synthetic efficiency and operational simplicity, and
      only water was generated as a byproduct.

PMID- 30296832
TI  - Adipose-Derived Mesenchymal Stromal Cells Persist in Tissue-Engineered Vocal Fold
      Replacement in Rabbits.
AB  - OBJECTIVES:: Cell therapies using mesenchymal stromal cells (MSCs) have been
      proposed as a promising new tool for the treatment of vocal fold scarring.
      However, the mechanisms by which MSCs promote healing as well as their duration
      of survival within the host vocal fold have yet to be defined. The aim of this
      work was to assess the persistence of embedded MSCs within a tissue-engineered
      vocal fold mucosal replacement in a rabbit model of vocal fold injury. METHODS::
      Male rabbit adipose-derived MSCs were embedded within a 3-dimensional fibrin gel,
      forming the cell-based outer vocal fold replacement. Four female rabbits
      underwent unilateral resection of vocal fold epithelium and lamina propria and
      reconstruction with cell-based outer vocal fold replacement implantation.
      Polymerase chain reaction and fluorescent in situ hybridization for the sex
      determining region of the Y chromosome (SRY-II) in the sex-mismatched donor
      recipient pairs sought persistent cells after 4 weeks. RESULTS:: A subset of
      implanted male cells was detected in the implant site at 4 weeks. Many SRY-II
      negative cells were also detected at the implant site, presumably representing
      native female cells that migrated to the area. No SRY-II signal was detected in
      contralateral control vocal folds. CONCLUSIONS:: The emergent tissue after
      implantation of a tissue-engineered outer vocal fold replacement is derived both
      from initially embedded adipose-derived stromal cells and infiltrating native
      cells. Our results suggest this tissue-engineering approach can provide a well
      integrated tissue graft with prolonged cell activity for repair of severe vocal
      fold scars.

PMID- 30296833
TI  - Disseminated Intravascular Coagulation: An Update on Pathogenesis, Diagnosis, and
      Therapeutic Strategies.
AB  - Disseminated intravascular coagulation (DIC) is an acquired clinicobiological
      syndrome characterized by widespread activation of coagulation leading to fibrin
      deposition in the vasculature, organ dysfunction, consumption of clotting factors
      and platelets, and life-threatening hemorrhage. Disseminated intravascular
      coagulation is provoked by several underlying disorders (sepsis, cancer, trauma,
      and pregnancy complicated with eclampsia or other calamities). Treatment of the
      underlying disease and elimination of the trigger mechanism are the cornerstone
      therapeutic approaches. Therapeutic strategies specific for DIC aim to control
      activation of blood coagulation and bleeding risk. The clinical trials using DIC
      as entry criterion are limited. Large randomized, phase III clinical trials have
      investigated the efficacy of antithrombin (AT), activated protein C (APC), tissue
      factor pathway inhibitor (TFPI), and thrombomodulin (TM) in patients with sepsis,
      but the diagnosis of DIC was not part of the inclusion criteria. Treatment with
      APC reduced 28-day mortality of patients with severe sepsis, including patients
      retrospectively assigned to a subgroup with sepsis-associated DIC. Treatment with
      APC did not have any positive effects in other patient groups. The APC treatment
      increased the bleeding risk in patients with sepsis, which led to the withdrawal
      of this drug from the market. Treatment with AT failed to reduce 28-day mortality
      in patients with severe sepsis, but a retrospective subgroup analysis suggested
      possible efficacy in patients with DIC. Clinical studies with recombinant TFPI or
      TM have been carried out showing promising results. The efficacy and safety of
      other anticoagulants (ie, unfractionated heparin, low-molecular-weight heparin)
      or transfusion of platelet concentrates or clotting factor concentrates have not
      been objectively assessed.

PMID- 30296834
TI  - Awareness and understanding of dementia in South Asians: A synthesis of
      qualitative evidence.
AB  - Background Despite a growing elderly South Asian population, little is known
      about the experience of diagnosis and care for those living with dementia. There
      have been a number of individual qualitative studies exploring the experiences of
      South Asian people living with dementia and their carers across different
      contexts. There has also been a growing interest in synthesizing qualitative
      research to systematically integrate qualitative evidence from multiple studies
      to tell us more about a topic at a more abstract level than single studies alone.
      The aim of this qualitative synthesis was to clearly identify the gaps in the
      literature and produce new insights regarding the knowledge and understanding of
      the attitudes, perceptions, and beliefs of the South Asian community about
      dementia. Methods Following a systematic search of the literature, included
      qualitative studies were assessed by two independent reviewers for methodological
      quality. Data were extracted and pooled using the Joanna Briggs Institute
      Qualitative Assessment and Review Instrument (QARI). Findings were synthesized
      using the Joanna Briggs Institute approach to qualitative synthesis by meta
      aggregation. Results Seventeen papers were critically appraised, with 13 meeting
      the inclusion criteria. Participants were mostly of South Asians of Indian
      background; followed by Pakistani with a few Sri Lankans. Missing South Asian
      countries from the current evidence base included those from Bangladesh, Bhutan,
      Maldives, and Nepal. Three meta-synthesis themes emerged from the analysis: (1) a
      poor awareness and understanding of dementia, (2) the experience of caregiving,
      and (3) the attitudes toward dementia care provision. Conclusions A consistent
      message from this qualitative synthesis was the limited knowledge and
      understanding of dementia amongst the South Asians. Whilst symptoms of dementia
      such as 'memory loss' were believed to be a part of a normal ageing process, some
      South Asian carers viewed dementia as demons or God's punishments. Most studies
      reported that many South Asians were explicit in associating stigmas with
      dementia.

PMID- 30296835
TI  - Prognostic Significance of Platelet Recovery in Myelodysplastic Syndromes With
      Severe Thrombocytopenia.
AB  - Severe thrombocytopenia is a serious condition that frequently arises in patients
      with myelodysplastic syndrome (MDS) and is associated with poor prognosis. Few
      studies have investigated the prognostic significance of platelet recovery in
      patients with MDS having thrombocytopenia. We retrospectively analyzed 117
      patients with de novo MDS complicated with thrombocytopenia (platelet count [PLT]
      < 100 * 109/L). Patients received decitabine treatment (schedule A) or decitabine
      followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT;
      schedule B). Severe thrombocytopenia (PLT < 20 * 109/L), identified in 31 (26.5%)
      patients, was associated with poor survival. The PLT increased significantly
      after decitabine treatment in the 2 groups. Patients with thrombocytopenia
      treated with schedule B showed a superior prognosis compared to those treated
      with schedule A. On analysis of overall survival by platelet response in patients
      with severe thrombocytopenia, a significant survival advantage was observed in
      patients who achieved a platelet response, who would further benefit from allo
      HSCT following decitabine therapy. The results indicate a potentially favorable
      prognostic impact of platelet response achieved with decitabine. Patients with
      MDS having severe thrombocytopenia may benefit from the effective recovery of
      platelets and further allo-HSCT following decitabine therapy.

PMID- 30296836
TI  - Mapping Genes Is Good for You.
AB  - I abandoned my original career choice of high school teaching to pursue dentistry
      and soon abandoned that path for genetics. The latter decision was due to a
      challenge by a professor that led to me reading Nobel speeches by pioneer
      geneticists before I had formal exposure to the subject. Even then, I was 15
      years into my career before my interest in rodent genomes gave way to mapping
      cattle genes. Events behind these twists and turns in my career path comprise the
      first part of this review. The remainder is a review of the development of the
      field of bovine genomics from my personal perspective. I have had the pleasure of
      working with outstanding graduate students, postdocs, and colleagues to
      contribute my small part to a discipline that has evolved from a few individuals
      mapping an orphan genome to a discipline underlying a revolution in animal
      breeding. Expected final online publication date for the Annual Review of Animal
      Biosciences Volume 7 is February 15, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30296837
TI  - Ethnic differences in hypertension prevalence and contributing determinants - the
      HELIUS study.
AB  - AIMS: There are important ethnic differences in the prevalence of hypertension
      and hypertension-mediated cardiovascular complications, but there is ongoing
      debate on the nature of these differences. We assessed the contribution of
      lifestyle, socio-economic and psychosocial variables to ethnic differences in
      hypertension prevalence. METHODS: We used cross-sectional data from the Healthy
      Life In an Urban Setting (HELIUS) study, including 21,520 participants aged 18-70
      years of South-Asian Surinamese ( n = 3032), African Surinamese ( n = 4124),
      Ghanaian ( n = 2331), Turkish ( n = 3594), Moroccan ( n = 3891) and Dutch ( n =
      4548) ethnic origin. Ethnic differences in hypertension prevalence rates were
      examined using logistic regression models. RESULTS: After adjustment for a broad
      range of variables, significant higher hypertension prevalence compared to the
      Dutch population remained in Ghanaian men (odds ratio 2.62 (95% confidence
      interval 2.14-3.22)) and women (4.16 (3.39-5.12)), African Surinamese men (1.62
      (1.37-1.92)) and women (2.70 (2.29-3.17)) and South-Asian Surinamese men (1.22
      (1.15-1.46)) and women (1.84 (1.53-2.22)). In contrast, Turkish men (0.72 (0.60
      0.87)) and Moroccan men (0.50 (0.41-0.61)) and women (0.57 (0.46-0.71)) had a
      lower hypertension prevalence compared with the Dutch population. The differences
      in hypertension prevalence were present across different age groups and persisted
      after stratification for body mass index and waist-to-hip ratio. CONCLUSION:
      Large ethnic differences in hypertension prevalence exist that are already
      present in young adulthood. Adjustment for common variables known to be
      associated with a higher risk of hypertension explained the higher adjusted
      prevalence rates among Turks and Moroccans, but not in African and South-Asian
      descent populations who remained to have a higher rate of hypertension compared
      to the Dutch host population.

PMID- 30296838
TI  - Vitamin D Status in Children With Hemato-Oncological Diseases in Northern
      Finland.

PMID- 30296839
TI  - Water quality comparison between a supply network and household reservoirs in one
      of the oldest cities in Brazil.
AB  - Water is an essential good for human life. This study aimed to verify the effects
      of household reservoirs on the physicochemical and microbiological
      characteristics of water in the municipality of Sao Mateus, Brazil, founded on 21
      September 1544. Samples were collected in 83 residences, two samples per
      residence, one from the supply network and another from the household reservoir,
      making a total of 166 samples. The pH values, the free residual chlorine content
      and the turbidity values were determined. For the microbiological analysis, the
      defined substrate technology was used, allowing the simultaneous detection and
      identification of total coliforms and Escherichia coli. The results showed that
      the samples from household reservoirs were more contaminated than those from the
      public supply network (p = 0.008). The high degree of microbiological
      contamination of the two groups may be directly associated to the reduced
      residual chlorine content in the samples, especially those from household
      reservoirs.

PMID- 30296840
TI  - Cerebral autoregulation in migraine with aura: A case control study.
AB  - Background Migraine with aura is independently associated with increased risk of
      ischemic stroke, especially in younger subjects. This association might be
      related to an impairment of cerebral autoregulation, which normally maintains
      cerebral blood flow independent of arterial blood pressure variations. Methods
      Patients aged 30-55, fulfilling ICHD-3 beta criteria for migraine with aura, were
      prospectively enrolled and compared with gender- and age-matched healthy controls
      without a history of migraine. Patients and controls with a history of stroke or
      any disease potentially impairing cerebral autoregulation were excluded. We
      assessed cerebral autoregulation with two different methods: Transfer function
      analysis, and the correlation coefficient index Mx. The transfer function phase
      and gain reflect responses of cerebral blood flow velocities to relatively fast
      fluctuations of arterial blood pressure, whereas Mx also reflects responses to
      slower arterial blood pressure fluctuations. Results A total of 22 migraine with
      aura patients (median age [IQR]: 39.5 [12.5] years) and 22 controls (39 [9.75]
      years) were included. Transfer function parameters and Mx were not different
      between patients and controls. However, Mx was inversely correlated with age in
      patients (rho = -0.567, p = 0.006) and not in controls (rho = -0.084, p = 0.509).
      Mx was also inversely correlated with migraine with aura duration (rho = -0.617,
      p = 0.002), suggesting improvement of cerebral autoregulation efficiency with
      disease duration. Conclusions Cerebral autoregulation did not differ between
      patients and controls aged 30-55. However, cerebral autoregulation efficiency was
      strongly correlated with migraine with aura duration. Further studies in younger
      patients are needed to determine whether cerebral autoregulation is impaired
      early in the course of disease. Trial Registration NCT02708797.

PMID- 30296841
TI  - Improving Patient Experience of Care Providers in a Multispecialty Ambulatory
      Pediatrics Practice.
AB  - Patient experience is positively associated with superior medical outcomes,
      clinical quality, patient safety measures, physician job satisfaction, doctor
      patient communication, and patient compliance with treatment recommendations. A
      concrete pediatrics-focused methodology for improving patient experience in a
      multispecialty ambulatory setting has not been described, nor has the impact on
      practice outcomes been assessed. The primary aim of this study was to improve
      patient experience care provider scores at a single multiclinic children's
      hospital in the Midwest to the 70th percentile in a 5-year period. The secondary
      aim sought to determine the impact of quality improvement efforts on practice
      growth, patient complaint rate, and provider/staff engagement. Patient experience
      was measured by returned Press-Ganey surveys. Interventions involved establishing
      infrastructure, promoting feedback and transparency, providing education, and
      transforming culture. Provider scores improved from the 19th to the 70th
      percentile within 5 years. Practice volume increased by 17.1%; patient
      complaint/grievance frequency decreased 33-fold; and provider/staff engagement
      did not appreciably change.

PMID- 30296842
TI  - Altered Mental Status in a Young Child: A Case of Child Neglect.

PMID- 30296843
TI  - Polysomnographic Findings in Patients With Chronic Tinnitus.
AB  - OBJECTIVES:: Tinnitus is an auditory sensation in the absence of any external
      stimulus. It has a negative impact on quality of life and interferes with
      concentration, sleep, social activities, and even emotional stability. The aim of
      this study was to compare sleep architecture in patients with and without chronic
      subjective tinnitus. METHODS:: This was an observational, noninterventional, and
      prospective study. The sample consisted of 50 individuals of both sexes aged 20
      to 60 years. Twenty-five patients with tinnitus constituted the study group, and
      for comparison, a control group consisting of 25 patients without reported
      tinnitus was formed. The patients underwent polysomnography and were administered
      the Epworth Sleepiness Scale, Tinnitus Handicap Inventory, and visual analog
      scales. RESULTS:: The group with tinnitus had higher mean values in sleep stages
      1 and 2, and lower mean values in stage 3 and in rapid eye movement (REM) sleep,
      compared with the control group, and this difference was significant only for REM
      sleep ( P = .031). This demonstrates that patients with tinnitus remained longer
      in shallow sleep and spent less time in deep sleep (stage 3) and REM sleep.
      CONCLUSIONS:: This study shows that patients with tinnitus have significant
      alterations in REM sleep latency as well as the REM sleep phase.

PMID- 30296844
TI  - Oral Sensory-Motor Intervention for Children and Adolescents (3-18 Years) With
      Dysphagia or Impaired Saliva Control Secondary to Congenital or Early-Acquired
      Disabilities: A Review of the Literature, 2000 to 2016.
AB  - OBJECTIVES:: Dysphagia and impaired saliva control are common in children and
      adolescents with congenital and developmental disabilities. The aim of the
      present review was to investigate the evidence base for oral sensory-motor
      interventions in children and adolescents with dysphagia or impaired saliva
      control secondary to congenital or early-acquired disabilities and to make
      recommendations regarding methods for intervention. METHODS:: A review of the
      literature from 2000 to 2016, including oral sensory-motor intervention studies
      for children and adolescents (3-18 years of age) with dysphagia or impaired
      saliva control secondary to congenital or early-acquired disabilities, was
      performed. The literature search included the PubMed, CINAHL, Medline,
      SpeechBITE, OVID, ERIC, Cochrane, and Google Scholar databases. Primary studies
      were evaluated on a 4-grade scale using the Grading of Recommendations
      Assessment, Development and Evaluation. RESULTS:: Twenty primary studies of oral
      sensory-motor interventions for dysphagia and 6 studies for the treatment of
      impaired saliva control fulfilled the inclusion criteria. Of these, 3 were
      randomized, controlled trials. Five systematic reviews and 16 narrative reviews
      were also included. Limited and moderately strong recommendations were made on
      the basis of the grading results from the primary studies. The studies reported
      good results, but study design was often insufficient, and the study groups were
      small. The systematic reviews confirmed the lack of high scientific support for
      oral sensory-motor interventions in children and adolescents with congenital and
      developmental disabilities. CONCLUSIONS:: There is an urgent need for high
      quality studies that could serve as the basis for strong recommendations relating
      to oral sensory-motor interventions for children with dysphagia and impaired
      saliva control.

PMID- 30296845
TI  - Outcomes of children receiving Group-Early Start Denver Model in an inclusive
      versus autism-specific setting: A pilot randomized controlled trial.
AB  - A major topic of debate is whether children with autism spectrum disorder should
      be educated in inclusive or specialized settings. We examined the feasibility and
      preliminary effectiveness of delivering the Group-Early Start Denver Model to
      children with autism spectrum disorder in inclusive versus specialized
      classrooms. We randomly assigned 44 preschoolers with autism spectrum disorder to
      receive the Group-Early Start Denver Model across one school calendar year in
      classrooms that included only children with autism spectrum disorder or mostly
      children who were typically developing. Blind-rated indicators of teaching
      quality showed similar results across settings, which were above the local
      benchmark. Children showed improvements across blinded proximal measures of
      spontaneous vocalization, social interaction, and imitation and across distal
      measures of verbal cognition, adaptive behavior, and autism symptoms irrespective
      of intervention setting. Mothers of participants experienced a reduction in
      stress irrespective of child intervention setting. Across both settings, age at
      intervention start was negatively associated with gains in verbal cognition.
      Delivery of Group-Early Start Denver Model in an inclusive setting appeared to be
      feasible, with no significant differences in teaching quality and child
      improvements when the program was implemented in inclusive versus specialized
      classrooms.

PMID- 30296846
TI  - Do the Low WHRs and BMIs Judged Most Attractive Indicate Higher Fertility?
AB  - We examine the widely accepted view that very low waist-hip ratios and low body
      mass indices (BMIs) in women in well-nourished populations are judged attractive
      by men because these features reliably indicate superior fertility. In both
      subsistence and well-nourished populations, relevant studies of fertility do not
      support this view. Rather studies indicate lower fertility in women with
      anthropometric values associated with high attractiveness. Moreover, low maternal
      BMI predisposes to conditions that compromise infant survival. Consistent with
      these findings from the literature, new data from a large U.S. sample of women
      past reproductive age show that women with lower BMIs in the late teens had fewer
      live births, controlling for education, marital history, and race. They also had
      later menarche and earlier menopause compared with women with higher youth BMIs.
      In addition, data from the 2013 U.S. natality database show that mothers with
      lower prepregnancy BMIs have an increased risk of producing both low-birth-weight
      and preterm infants controlling for other relevant variables-conditions that
      would have adversely affected fitness over almost all of human evolution. Thus, a
      review of the relevant literature and three new tests fail to support the view
      that highly attractive women are more fertile.

PMID- 30296847
TI  - Potential benefits of the cognitive orientation to daily occupational performance
      approach in young adults with spina bifida or cerebral palsy: a feasibility
      study.
AB  - PURPOSE: People with cerebral palsy (CP) or spina bifida (SB) often struggle to
      perform everyday-life activities. Both groups frequently also have difficulties
      in creating and using strategies effectively when performing tasks. The cognitive
      orientation to daily occupational performance (CO-OP) Approach combines the
      learning of cognitive strategies with task-specific approaches through a client
      centred procedure. The aim of this study was to investigate whether the CO-OP
      Approach is feasible for and potentially beneficial to adolescents and young
      adults with CP or SB in Sweden by analysing four areas of feasibility
      (acceptability, efficacy, adaptation, and expansion). METHODS: Exploratory
      multiple-case study using mixed methods. Ten persons aged 16-28, five with each
      condition, participated in an intervention period. Assessments were performed on
      three occasions: baseline, post-intervention, and six-month follow-up. RESULTS:
      The result demonstrates that the CO-OP Approach has the potential to enable
      adolescents and young adults with either condition to achieve personal goals and
      to enhance their planning skills and their ability to use strategies when
      performing activities. This approach is also compatible with the core values of
      habilitation in Sweden and was found by the participants to be highly meaningful
      and useful. CONCLUSIONS: The CO-OP Approach is feasible for adolescents and young
      adults with SB or CP in Sweden. Implications for rehabilitation The Cognitive
      Orientation to daily Occupational Performance * is a feasible approach for
      adolescents and young adults with spina bifida and with cerebral palsy. * is a
      promising approach when it comes to enabling the achievement of personal goals. *
      might have potential to enhance executive functioning through strategy use. * is
      in line with the fundamental core values of disability rights of inclusion,
      empowerment, and participation.

PMID- 30296848
TI  - Analysis of Failed Ankle Arthroplasty Components.
AB  - BACKGROUND: Although advances in joint-replacement technology have made total
      ankle arthroplasty a viable treatment for end-stage arthritis, revision rates for
      ankle replacements are higher than in hip or knee replacements. The questions
      asked in this study were what can retrieved ankle devices demonstrate about ankle
      arthroplasty failures and how can understanding the causes of these failures
      inform clinical decisions for current and future ankle arthroplasty patients?
      METHODS: An IRB-approved retrieval laboratory received retrieved components and
      surgeon-supplied reason for revision from 70 total-ankles (7 designs, including 5
      currently marketed designs) from 2002 to 2018. These retrievals were rated for
      clinical wear and damage. Metal components were rated by method and effectiveness
      of fixation. Polyethylene inserts received by the laboratory 6 months or less
      after retrieval (n = 45) were analyzed for oxidation using Fourier transform
      infrared spectroscopy. Statistical analysis was performed using IBM SPSS, version
      22. RESULTS: The ankle implants were retrieved most commonly for loosening and
      polyethylene fracture. Loosening occurred more frequently in fixed-bearing
      designs (n = 18) than in the mobile-bearing designs (n = 4) and after shorter in
      vivo time (mean in vivo time to retrieval for loosening: fixed bearing 3.2 +/-
      2.1 years, mobile bearing 9.7 +/- 4.5 years). Gamma-sterilized ankle inserts
      oxidized at a higher rate than non-gamma (EtO or gas-plasma) sterilized ankle
      inserts (gamma 0.29 +/- 0.22/y, non-gamma 0.07 +/- 0.05/y, mean difference=0.215,
      95% CI 0.128-0.303, P < .001). The presence of clinical fatigue (cracking and/or
      delamination) of the polyethylene insert correlated with measured oxidation
      (Spearman rho = 0.685, P < .001). Nine inserts, all gamma-sterilized, fractured
      in vivo. CONCLUSIONS: This study suggests that loosening could be more of a
      problem in fixed-bearing devices than in mobile bearing devices. Gamma-sterilized
      polyethylene inserts were found to suffer fatigue damage or fracture in vivo,
      resulting in the need for revision. Retrieval analysis can provide insight into
      implant-related reasons for revision, with the goal of understanding the implant
      related causes of these failures, informing future ankle design and clinical
      decisions for current and future ankle arthroplasty patients. LEVEL OF EVIDENCE:
      Level III, comparative series.

PMID- 30296849
TI  - Do the Low WHRs and BMIs Judged Most Attractive Indicate Better Health?
AB  - It is widely claimed that in well-nourished populations, very low female waist
      hip ratios (WHRs) together with low body mass indices (BMIs) are judged
      attractive by men because these features reliably indicate superior health and
      fertility. However, studies show that mortality rates are higher in women with
      low BMIs than in women with average BMIs and are inversely related to BMI in
      subsistence populations. Measures of current health in women of reproductive age
      have not been similarly studied. We analyze large U.S. samples of reproductive
      age women and show that controlling for other factors known to affect health,
      those with low BMIs (<20), WHRs, or waist/stature ratios did not have better
      health than those with values in the middle range, and there was no relationship
      between subsequent health outcomes and BMI in early adulthood. Lower self
      reported BMIs were linked to poorer health and an increased risk of infection.
      However, based on recent U.S. natality data, primiparas with lower BMIs had a
      lower risk of an operative delivery and of gestational hypertension. Beyond these
      two parity-restricted effects, relevant studies and new tests fail to support the
      view that women with the very low BMIs and WHRs consistently judged attractive
      are generally healthier than women with average values; significant correlations
      were consistently in the opposite direction.

PMID- 30296850
TI  - Menopausal hormone therapy and breast cancer: what is the evidence from
      randomized trials?
AB  - The relationship between menopausal hormone therapy (HT) and breast cancer is
      complex and further complicated by misinformation, perception, and
      overgeneralization of data. These issues are addressed in this mini-review
      through the lens of the Women's Health Initiative (WHI) that has colored the view
      of HT and breast cancer. In the WHI, unopposed conjugated equine estrogen (CEE)
      reduced breast cancer risk and mortality. In the WHI CEE plus continuously
      combined medroxyprogesterone acetate (MPA) trial, although the hazard ratio (HR)
      was elevated it was statistically non-significant for an association between CEE
      + MPA and breast cancer. In fact, the increased HR was not due to an increased
      breast cancer incidence rate in women randomized to CEE + MPA therapy but rather
      due to a decreased and unexpectedly low breast cancer rate in the subgroup of
      women with prior HT use randomized to placebo. For women who were HT naive when
      randomized to the WHI, the breast cancer incidence rate was not affected by CEE +
      MPA therapy relative to placebo for up to 11 years of follow-up. The current
      state of science indicates that HT may or may not cause breast cancer but the
      totality of data neither establish nor refute this possibility. Further, any
      association that may exist between HT and breast cancer appears to be rare and no
      greater than other medications commonly used in clinical medicine.

PMID- 30296851
TI  - Medical Marijuana Laws and Marijuana Use Among U.S. Adolescents: Evidence From
      Michigan Youth Risk Behavior Surveillance Data.
AB  - Research findings are inconsistent regarding a positive association between the
      passage of state medical marijuana laws (MML) and the adolescent access and the
      use of marijuana. We utilized a novel analytical approach to examine this issue
      with multiyear data from the 1997-2013 Youth Risk Behavior Surveillance System of
      the State of Michigan. After controlling for the historically declining trend in
      marijuana use prior to the passages of MML in Michigan, we found that marijuana
      use among adolescents had increased subsequent to the passage of state MML. The
      study findings suggest the need for considering the increased risk of marijuana
      use in adolescents, as more states have implemented laws permitting marijuana
      use.

PMID- 30296853
TI  - The Influence of Latino Symptom Experience on Participation in Usual Activities
      and Satisfaction With Participation in Social Roles.
AB  - INTRODUCTION:: Little is known about the Latino symptom experience and how
      symptoms influence participation in usual activities and satisfaction with
      participation in social roles. METHOD:: Secondary analysis of survey data
      collected in community and clinic settings was conducted. Data were collected
      using Health-Related Quality of Life 30-day items and Patient Reported Outcome
      Measurement System symptom status scales. Descriptive statistics and univariate
      linear and multiple linear regression models were computed. RESULTS::
      Participants ( N = 2,974) were primarily female and Dominican. Most surveys were
      completed in Spanish and in the community setting; and the clinic sample had more
      symptoms. In the multiple linear regression for participation in usual
      activities, as the number of days with symptoms increased, the number of days
      that poor physical or mental health influenced participation in usual activities
      increased. In addition, for satisfaction with participation in social roles, as
      the number of days with pain and levels of depression and anxiety increased, the
      levels of satisfaction decreased. Spanish survey administration was associated
      with decreased levels of satisfaction; and recruitment setting was not a
      significant predictor. CONCLUSION:: The study addressed multiple knowledge gaps
      about the Latino symptom experience.

PMID- 30296854
TI  - Royal jelly does not prevent bone loss but improves bone strength in
      ovariectomized rats.
AB  - OBJECTIVE: Royal jelly (RJ) has been used for medical and nutritional purposes,
      and previous studies have indicated that it may have estrogenic activity. The
      present study investigated the effects of RJ on bone metabolism in ovariectomized
      (OVX) rats. METHODS: Rats (12 weeks old) were randomly divided into four groups,
      namely Baseline, Sham, OVX, and OVX + RJ groups. Rats in the Baseline group were
      killed immediately, whereas rats in the OVX and OVX + RJ groups underwent
      bilateral ovariectomy and those in the Sham group underwent sham operation. RJ
      was administered to rats in the OVX + RJ group daily for 12 weeks. At the end of
      the 12-week period, bone mass, bone histomorphometry, and bone mechanics were
      analyzed. RESULTS: Femur bone mineral density (BMD) was significantly lower in
      the OVX group than in the Sham group, and this decrease in BMD was not
      ameliorated by RJ administration. However, femur stiffness, as evaluated by a
      three-point bending test, was significantly higher in the OVX + RJ group than in
      the OVX group. CONCLUSION: The findings of the present study suggest that RJ does
      not prevent bone loss, but does improve bone strength in OVX rats.

PMID- 30296852
TI  - Discovery of novel 1,3-diaryltriazene sulfonamides as carbonic anhydrase I, II,
      VII, and IX inhibitors.
AB  - A series of new 1,3-diaryltriazene sulfonamides was synthesised by reaction of
      diazonium salt of metanilamide (3-aminobenzene sulfonamide) with substituted
      aromatic amines. The obtained new compounds were assayed as inhibitors of four
      physiologically and pharmacologically relevant human (h) isoforms of carbonic
      anhydrases (CA, EC 4.2.1.1), specifically, hCA I, hCA II, and hCA VII (cytosolic
      isoforms), as well as the tumour-associated membrane-bound isoform hCA IX. All
      isoforms investigated here were inhibited by the newly synthesised 1,3
      diaryltriazene sulfonamide derivatives from the micromolar to the nanomolar
      range. The cytosolic isoforms were inhibited with Kis in the range of 92.3-8371.1
      nM (hCA I), 4.3-9194.0 nM (hCA II), and 15.6-9477.8 nM (hCA VII), respectively.
      For the membrane-bound tumour-associated isoform hCA IX, the KI-s ranged between
      50.8 and 9268.5 nM. The structure-activity relationship (SAR) with these newly
      synthesised metanilamide derivatives are discussed in detail.

PMID- 30296855
TI  - Effects of Onchung-eum, an Herbal Prescription, on 5-Fluorouracil-Induced Oral
      Mucositis.
AB  - In most cancer patients, chemotherapy-induced oral mucositis (OM) is a frequent
      side effect, leading to low quality of life and delay in therapy. The aim of this
      study was to evaluate the effects of Onchung-eum, a well-known herbal
      prescription in traditional medicine comprising 8 herbs that has long been used
      for skin diseases, on 5-fluorouracil (5-FU)-induced OM in human pharyngeal cells
      and golden Syrian hamsters. DPPH (2,2-diphenyl-1-picrylhydrazyl) radical
      scavenging activity, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide) assay, and reactive oxygen species production were measured in vitro.
      The effects of Onchung-eum on OM of hamster cheek pouches induced by 5-FU were
      evaluated histologically and using TUNEL assay. In addition, the expression of
      nuclear factor-kappaB, caspase-3, and pro-inflammatory cytokines were measured by
      immunoblotting and immunohistochemistry. Significantly increased cell viability
      was observed in the Onchung-eum-treated groups compared with the 5-FU-treated
      control group. In 500 and 1000 mg/kg Onchung-eum-treated groups, the damaged
      epithelial layers in the cheek pouches of hamsters were significantly recovered.
      Moreover, at all concentrations, cell death in the cheek pouches of hamsters in
      the Onchung-eum-treated groups significantly decreased. The expression of pro
      inflammatory cytokines, nuclear factor-kappaB, and caspase-3 also significantly
      decreased in Onchung-eum-treated groups at 500 and 1000 mg/kg. In conclusion,
      this study revealed that Onchung-eum can be used to treat chemotherapy-induced
      OM. However, further studies are required to understand the underlying
      mechanisms.

PMID- 30296856
TI  - The Swedish motor neuron disease quality registry.
AB  - OBJECTIVE: We set up the Swedish Motor Neuron Disease (MND) Quality Registry to
      assure early diagnosis and high-quality health care for all MND patients (mainly
      amyotrophic lateral sclerosis, ALS), and to create a research base by
      prospectively following the entire MND population in Sweden. METHODS: Since 2015,
      the MND Quality Registry continuously collects information about a wide range of
      clinical measures, biological samples, and quality of life outcomes from all MND
      patients recruited at the time of MND diagnosis in Sweden and followed at each
      clinic visit approximately every 12 weeks. The Registry includes an Internet
      based patient own reporting portal that involves patients in the registration of
      their current symptoms and health status. RESULTS: As of 20th January 2017, the
      MND Quality Registry included 99% of the MND patients of the Stockholm area (N =
      194), consisting mostly of ALS patients (N = 153, 78.9%), followed by patients
      labeled as MND due to a neurophysiology finding but not fulfilling the criteria
      for ALS (N = 20, 10.3%), primary lateral sclerosis (N = 13, 6.7%), and
      progressive spinal muscular atrophy patients (N = 8, 4.1%). A higher proportion
      of these patients were women (N = 100, 52%), and women and men had a similar age
      at symptoms onset (59 years). CONCLUSIONS: Main strengths of the MND Quality
      Registry are its clinical, quantitative, qualitative, and prospective nature,
      providing the researchers potential means of identifying appropriate candidates
      for clinical trials and other research projects, as well as assuring to the
      patients an effective and adequate time spent on-site with the healthcare
      professionals.

PMID- 30296857
TI  - Between medicalisation and normalisation: Antithetical representations of
      depression in the Greek-Cypriot press in times of financial crisis.
AB  - Media offer people ways of understanding mental health and illness, shaping their
      attitudes and behaviour towards it. Yet, the literature on media representations
      of depression is limited and fails to illuminate sufficiently the content of
      representations. In times of financial crisis, the prevalence of depression is
      increased and the particular meanings associated with depression are widely
      diffused. To unpack these meanings, we focused on the Greek-Cypriot press during
      the financial crisis of 2013. Two-hundred and three articles from seven widely
      circulating newspapers were thematically analysed. Two antithetical themes of
      representations of depression were identified: Biomedical Depression, which
      constructed depression as a biologically grounded illness treated through
      medical/pharmaceutical means, and Everyday Depression, which portrayed depression
      as something normal, encountered in anyone, attributed to psychosocial factors
      (e.g. the financial crisis), and treated through self-management. Biomedical
      Depression reflects a widespread medical and deterministic understanding of
      depression. Nevertheless, this understanding has not overridden, as the
      literature suggests, references to individual agency, which are present in the
      Everyday Depression and the more normalising understanding of depression it
      expresses. We argue, however, that both themes promote an individualistic
      understanding of depression, placing individuals in a tense position of being
      responsible for a condition perceived to be outside their control.

PMID- 30296858
TI  - Movement and Demography of At-Risk Butterflies: Building Blocks for Conservation.
AB  - The number of insect species at risk of population decline and extinction is
      increasing rapidly. Yet we know almost nothing about the ecology of these
      species, except for at-risk butterflies. A growing body of literature shows how
      butterfly vital rates, including demography and movement, are essential for
      guiding conservation and recovery. History has shown us that without these data,
      conservation decisions often weaken, rather than enhance, population viability.
      This is especially true in changing landscapes. We review knowledge of vital
      rates across all at-risk butterflies. We have information on movement for 17 of
      283 butterfly species and information on demography for 19 species. We find that
      habitat-specific movement behavior is key to understanding how to connect
      populations, and habitat-specific demography is central to managing habitats.
      Methods and analyses worked out for butterflies can provide a scaffold around
      which to build studies for the conservation of other at-risk insects. Expected
      final online publication date for the Annual Review of Entomology Volume 64 is
      January 7, 2019. Please see http://www.annualreviews.org/page/journal/pubdates
      for revised estimates.

PMID- 30296859
TI  - Movement Ecology of Pest Helicoverpa: Implications for Ongoing Spread.
AB  - The recent introduction and spread of Helicoverpa armigera throughout South
      America highlights the invasiveness and adaptability of moths in the Helicoverpa
      genus. Long-range movement in three key members, H. armigera, H. zea, and H.
      punctigera, occurs by migration and international trade. These movements
      facilitate high population admixture and genetic diversity, with important
      economic, biosecurity, and control implications in today's agricultural
      landscape. This is particularly true for the spread of resistance alleles to
      transgenic crops expressing Bacillus thuringiensis (Bt) toxins that are planted
      over vast areas to suppress Helicoverpa spp. The ability to track long-distance
      movement through radar technology, population genetic markers, and/or long
      distance dispersal modeling has advanced in recent years, yet we still know
      relatively little about the population trajectories or migratory routes in
      Helicoverpa spp. Here, we consider how experimental and theoretical approaches
      can be integrated to fill key knowledge gaps and assist management practices.
      Expected final online publication date for the Annual Review of Entomology Volume
      64 is January 7, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30296860
TI  - Proof of concept studies for siRNA delivery by non-ionic surfactant vesicles: in
      vitro and in vivo evaluation of protein knockdown.
AB  - RNA interference (RNAi) is an effective and naturally occurring post
      transcriptional gene regulatory mechanism. This mechanism involves the
      degradation of a target messenger RNA (mRNA) through the introduction of short
      interfering RNA (siRNA) that is complementary to the target mRNA. The application
      of siRNA-based therapeutics is limited by the development of an effective
      delivery system, as naked siRNA is unstable and cannot penetrate the cell
      membrane. In this study, we investigated the use of cationic niosomes (CN)
      prepared by microfluidic mixing for siRNA delivery. In an in vitro model, these
      vesicles were able to deliver anti-luciferase siRNA and effectively suppress
      luciferase expression in B16-F10 mouse melanoma cells. More importantly, in an in
      vivo mouse model, intratumoral administration of CN-carrying anti-luciferase
      siRNA led to significant suppression of luciferase expression compared with naked
      siRNA. Thus, we have established a novel and effective system for the delivery of
      siRNA both in vitro and in vivo, which shows high potential for future
      application of gene therapeutics.

PMID- 30296861
TI  - Psychosocial consequences among women with false-positive results after
      mammography screening in Norway.
AB  - BACKGROUND: Mammography screening may cause psychosocial harm for women
      experiencing a false-positive screening result. Previous studies suggest long
      term consequences. The aim of the present study was to assess psychosocial
      consequences of false-positive findings on screening mammography within a six
      month follow-up. METHODS: A prospective matched cohort survey study using the
      questionnaire 'Consequences of Screening for Breast Cancer' (COS-BC), which was
      translated from Danish to Norwegian. Psychometric analyses investigated the
      measurement properties of the Norwegian version. Two screening clinics in Norway
      distributed the survey to 299 women with an abnormal mammogram and 541 women with
      a normal screen. Women received the questionnaire when receiving the screening
      result, and one and six months after screening. RESULTS: At six months,
      statistically significant differences appeared in two scales: existential values
      and breast examination. At six-month follow-up, women with false-positive results
      showed no statistically significant differences from women diagnosed with breast
      cancer in three outcomes: sense of dejection, anxiety, and keeping my mind off
      things. CONCLUSION: Our results indicate that the psychosocial consequences from
      having false-positive screening mammography results diminish after six months.
      The results support previous research describing breast-specific outcomes.
      However, our results indicate that Norwegian women are less frightened than other
      Scandinavian mammography screening participants.

PMID- 30296862
TI  - Porphyrias and photosensitivity: pathophysiology for the clinician.
AB  - Porphyrias are disorders caused by defects in the biosynthetic pathway of heme.
      Their manifestations can be divided into three distinct syndromes, each
      attributable to the accumulation of three distinct classes of molecules. The
      acute neurovisceral syndrome is caused by the accumulation of the neurotoxic
      porphyrin precursors, delta aminolevulinic acid, and porphobilinogen; the
      syndrome of immediate painful photosensitivity is caused by the lipid-soluble
      protoporphyrin IX and, the syndrome of delayed blistering photosensitivity,
      caused by the water-soluble porphyrins, uroporphyrin, and coproporphyrin.
      Porphyrias can manifest with one, or with a combination, of these syndromes,
      depending on whether one or more types of molecules are being accumulated. Iron
      plays a significant role in some of these conditions, as evidenced by
      improvements in both clinical manifestations and laboratory parameters, following
      iron depletion in porphyria cutanea tarda, or iron administration in some cases
      of X-linked erythropoietic protoporphyria. While the pathophysiology of a
      specific type of porphyrias, the protoporphyrias, appears to favor the
      administration of zinc, results so far have been conflicting, necessitating
      further studies in order to assess its potential benefit. The pathways involved
      in each disease, as well as insights into their pathobiological processes are
      presented, with an emphasis on the development of photosensitivity reactions.

PMID- 30296864
TI  - Linezolid in children with drug resistant tuberculosis.

PMID- 30296863
TI  - Lung delivery of nanoliposomal salbutamol sulphate dry powder inhalation for
      facilitated asthma therapy.
AB  - The motive behind present work was to discover a solution for overcoming the
      problems allied with deprived oral bioavailability of salbutamol sulphate (SS)
      due to its first pass hepatic metabolism, shorter half life and systemic toxicity
      at high doses. Pulmonary delivery provides alternative route of administration to
      avoid hepatic metabolism of SS, moreover facilitated diffusion and prolonged
      retention can be achieved by incorporation into liposomes. Liposomes were
      prepared by thin film hydration technique using 32 full factorial design and
      formulation was optimized based on the vesicle size and percent drug entrapment
      (PDE) of liposomes. Optimized liposomal formulation exhibited average size of
      about 167.2+/-0.170 nm, with 80.68+/-0.74% drug entrapment, and 9.74+/-1.10 mV
      zeta potential. The liposomal dispersion was then spray dried and further
      characterized for in-vitro aerosol performance using Andersen Cascade Impactor.
      Optimized liposomal formulation revealed prolonged in-vitro drug release of more
      than 90% up to 14 h following Higuchi's controlled release model. Thus, proposed
      new-fangled liposomal formulation would be a propitious alternative to
      conventional therapy for efficient and methodical treatment of asthma and alike
      respiratory ailments.

PMID- 30296865
TI  - Novel abdominal approach for dissection of advanced type II/III adenocarcinoma of
      the esophagogastric junction: a new surgical option.
AB  - Objective The optimal surgical approach for Siewert type II adenocarcinoma of the
      esophagogastric junction (AEG) is controversial. In this study, we evaluated the
      outcomes of total gastrectomy for Siewert type II/III AEG via the left thoracic
      surgical approach that is used at our center. Methods We identified 41 patients
      with advanced AEG in our retrospective database and analyzed their 3-year
      survival rate, upper surgical margin, postoperative complications, and index of
      estimated benefit from lymph node dissection. Results The 3-year overall survival
      rate of the whole group was 63%, but no difference was observed between Siewert
      type II and III AEGs. Esophageal exposure and lymphadenectomy were sufficient.
      Eight patients developed postoperative complications, but none of the patients
      developed anastomotic leakage. Dissection of lymph node station Nos. 19 and 110
      may be necessary for patients with Siewert type II AEG. Multivariate analysis
      revealed that the cT category was the only independent risk factor. Conclusions
      Total gastrectomy via an approach from the abdominal cavity into the thoracic
      cavity may be an optimal surgical technique for advanced Siewert type II AEG.

PMID- 30296866
TI  - Mental adjustment to cancer and quality of life among women living with breast
      cancer in Ghana.
AB  - Objective This study examined whether cancer-specific coping strategies have any
      significant influence on the quality of life of 205 women living with breast
      cancer in Ghana. Methods Using a cross-sectional survey design, participants were
      administered questionnaires which measured their cancer-specific coping
      strategies and health-related quality of life. Results Correlation analysis
      showed that helplessness-hopelessness negatively correlated with physical
      wellbeing, emotional wellbeing, functional wellbeing, and breast cancer
      additional concerns. Anxious preoccupation negatively correlated with all the
      domains of quality of life, whereas fighting spirit was positively correlated
      with emotional and functional wellbeing. Cognitive avoidance was positively
      correlated with functional wellbeing, while fatalism was positively related with
      all the domains of quality of life. Regression analysis revealed that anxious
      preoccupation predicted significant decreases in all the domains of quality of
      life, while helplessness-hopelessness predicted significant decreases in
      emotional and functional wellbeing domains. However, cognitive avoidance
      predicted significant increase in the functional domain of quality of life.
      Conclusion These findings underscore the need for psychosocial support for breast
      cancer patients to adopt effective coping strategies to deal with their
      challenges in managing their illness.

PMID- 30296867
TI  - Delayed intranasal coil extrusion after internal carotid artery pseudoaneurysm
      embolization.
AB  - Internal carotid artery (ICA) injury is a rare but potentially life-threatening
      complication of skull base and neck surgery. Although usually manifested by
      massive intraoperative haemorrhage, impairment of the ICA might go unnoticed and
      result in formation of a pseudoaneurysm, causing delayed bleeding. Often
      additional complications are observed such as thrombosis, spasm, embolism or
      carotico-cavernous fistula formation. The risk of carotid artery injury in
      aggressive endonasal skull base surgical interventions ranges from 1% to 9%.
      Digital subtracted angiography remains the gold standard for evaluation of
      patients with iatrogenic carotid artery injury as it allows for endovascular
      treatment at the time of the procedure. Endovascular embolization is currently
      the preferred method for treating ICA pseudoaneurysms and a successful
      alternative to the surgical approach. Even though endovascular approaches are
      considered the safer option, delayed complications have been registered, such as
      endovascular coil extrusion and migration, which increases the risk of further
      episodes of bleeding. We present our experience with late coil extrusion in a
      patient who was previously treated with flow diverter stent and coiling for
      iatrogenic ICA pseudoaneurysm.

PMID- 30296869
TI  - Perceptions of Needs, Assets, and Priorities Among Black Men Who Have Sex With
      Men With HIV: Community-Driven Actions and Impacts of a Participatory Photovoice
      Process.
AB  - Black men who have sex with men (MSM) with HIV experience significant health
      inequities and poorer health outcomes compared with other persons with HIV. The
      primary aims of this study were to describe the needs, assets, and priorities of
      Black MSM with HIV who live in the Southern United States and identify actions to
      improve their health using photovoice. Photovoice, a participatory, collaborative
      research methodology that combines documentary photography with group discussion,
      was conducted with six Black MSM with HIV. From the photographs and discussions,
      primary themes of discrimination and rejection, lack of mental health services,
      coping strategies to reduce stress, sources of acceptance and support, and future
      aspirations emerged. After the photographs were taken and discussed, the
      participants hosted a photo exhibition and community forum for the public. Here,
      37 community attendees and influential advocates collaborated with the
      participants to identify 12 actions to address the men's identified needs,
      assets, and priorities. These included making structural changes in the legal and
      medical systems, encouraging dialogue to eliminate multiple forms of stigma and
      racism, and advocating for comprehensive care for persons with HIV. As a
      secondary aim, the impacts of photovoice were assessed. Participants reported
      enjoying photovoice and found it meaningful. Results suggest that in addition to
      cultivating rich community-based knowledge, photovoice may result in positive
      changes for Black MSM with HIV.

PMID- 30296868
TI  - Mesenchymal stromal cells in the treatment of perianal fistulas in Crohn's
      disease.
AB  - Significant unmet needs remain in patients with Crohn's disease and perianal
      fistulas. Mesenchymal stromal cells have potent immunomodulatory actions. The
      Phase II studies reported efficacy of local injection of mesenchymal stromal
      cells to achieve closure of fistulas. A Phase III trial demonstrated that in
      patients with Crohn's disease and refractory complex perianal fistulas, a single
      injection of 120 * 106 cells was superior to local injection of placebo
      associated with the same surgical procedure, in obtaining closure of the fistula
      tracts together with absence of abscesses >2 cm, 24 weeks after the injection, a
      stringent combined primary end point. The benefit over placebo was sustained 52
      weeks after the single injection. The therapy is safe with adverse events limited
      to local pain.

PMID- 30296870
TI  - Andexanet alfa for the treatment of hemorrhage.
AB  - INTRODUCTION: While associated life-threatening and fatal bleeding events are
      less frequent with the direct factor Xa inhibitors compared to vitamin K
      antagonists, significant concern surrounding management of major bleeds and
      urgent periprocedural interruption of these agents exists among clinicians.
      Andexanet alfa is a recombinant human factor Xa decoy protein developed in
      response to this clinical gap in the care of patients receiving anticoagulation
      with factor Xa inhibitors. Areas covered: This paper reviews results from
      preclinical and healthy-volunteer studies demonstrating the ability of andexanet
      to rapidly and reliably normalize coagulation indices in patients treated with
      both direct and indirect factor Xa inhibitors. An interim analysis from an
      ongoing phase 3/4b clinical study assessing the efficacy and safety of andexanet
      in patients experiencing life-threatening hemorrhage in association with factor
      Xa inhibitors is discussed. It also provides an overview of the major safety
      concerns reported in these trials which include allergic and infusion reactions,
      development of anti-andexanet antibodies and, importantly, thrombosis. Expert
      commentary: While initial reports on restoration of hemostasis and safety are
      promising, further study of andexanet is required to gauge its efficacy and
      toxicity, including a potential prothrombotic effect. Further, its use in
      patients requiring urgent surgery should be studied.

PMID- 30296871
TI  - Trends in primeval beta-hCG level increment after fresh and frozen-thawed IVF
      embryo transfer cycles.
AB  - Mid-trimester beta-human chorionic gonadotropin (BHCG) levels are considerably
      higher in pregnancies resulting from frozen embryo transfer (FET) compared with
      fresh (FRET), leading to a higher false positive rate in aneuploidy screening
      tests. We aimed to investigate the dynamics of BHCG increment and its predictive
      value for cycle outcome. A retrospective analysis of FRET and FET cycles. BHCG
      values on days 14 and 16 post embryo transfer were compared and stratified
      according to the number of sacs demonstrated on US scan at six weeks gestation,
      and pregnancy outcome (biochemical pregnancy, ectopic pregnancy, spontaneous
      abortion, and a singleton or twin birth). A prediction model for live birth was
      built. A total of 430 treatment cycles were analyzed. The average BHCG levels
      were significantly higher in FET compared with FRET group in nonviable
      pregnancies on day 14, 450 vs. 183 IU/L, p < .05 and day 16, 348 vs. 735 IU/L, p
      < .05, respectively. The increment of BHCG was significantly steeper in the FET
      compared with FRET group in biochemical pregnancies (F = 6.485, p = .012*).
      Optimal cutoff level for live birth prediction in the FRET group was 211 IU/L
      (sensitivity 84%, specificity 76.2%) for day 14 and 440 IU/L (sensitivity 86.0%
      and specificity 72.5%) for day 16. The increment in BHCG differed significantly
      between the FRET and FET cycles in nonviable pregnancies. Nevertheless, the
      difference in BHCG levels observed in the second trimester in pregnancies
      conceived after FRET and FET cycle may begin as early as the fourth week of
      pregnancy.

PMID- 30296872
TI  - Analysis of selected promoter polymorphisms and haplotypes of the CYBA gene
      encoding the p22phox, subunit of NADPH oxidases, in patients with coronary artery
      disease.
AB  - BACKGROUND: The p22phox is a critical component of vascular NADPH oxidases and is
      encoded by the CYBA gene. It was shown that functionally relevant polymorphisms
      of the CYBA gene - 930A>G, -852C>G , -675A>T , -536C>T, 214C>T (previously
      described as 242C>T), *24A>G (previously described as 640A>G), and *49A>G
      modulate generation of reactive oxygen species (ROS). AIM: Analyse whether the
      CYBA gene polymorphisms - 852C>G, -675A>T , and - 536C>T were associated with
      coronary artery disease (CAD), and to designate haplotype blocks. METHODS: Four
      hundred and ninety subjects: 245 patients with CAD and 245 age and sex matched
      controls. The polymorphisms were genotyped using the PCR-RFLP method and the
      TagMan(r) Pre-designed SNP Genotyping Assay. RESULTS: The analysed polymorphisms
      do not form haplotype blocks. Case-control study revealed that the -930 G/-675T
      and -930G /*49G diplotypes were a CAD risk factor. The 675T/*49G diplotype can
      modulate CAD risk in women. The protective effect reducing CAD risk in women was
      related to the -930A/-675T and -930A /*49A diplotypes. Carrier state of the -852C
      allele ( -852C>G ) was associated with multivessel stenosis while the CC genotype
      of the -536C>T polymorphism was more frequent in patients with peripheral artery
      disease. Hypercholesterolemic, cigarette smokers had an increased risk of CAD,
      especially C - 852 allele (-852C>G) carriers (SIM = 3.54; odds ratios (OR) =
      10.01, p < 0.000). CONCLUSIONS: The CYBA gene polymorphisms modulate the risk of
      CAD but do not form a haplotype blocks.

PMID- 30296873
TI  - Association between serum copper levels and lung cancer risk: A meta-analysis.
AB  - Objective To evaluate the association between serum copper levels and lung cancer
      risk. Methods We searched the electronic PubMed, WanFang, CNKI, and SinoMed
      databases to identify studies including information on serum copper levels and
      lung cancer. Standard mean differences and corresponding 95% confidence intervals
      were calculated using Stata 12.0 software. We performed a meta-analysis on the
      identified studies overall and according to geographic location. We also
      evaluated heterogeneity among the studies and the occurrence of publication bias.
      Results Thirty-three articles including 3026 cases and 9439 controls were
      included in our study. The combined results showed that serum copper levels were
      higher in patients with lung cancer compared with controls without lung cancer,
      though the results showed high heterogeneity. In a subgroup analysis according to
      geographic location, significant associations between copper levels and lung
      cancer were found for both Asian and European populations. No publication bias
      was detected in this meta-analysis. Conclusions High serum copper levels could
      increase the risk of lung cancer, suggesting that environmental copper exposure
      may be a risk factor for the development of lung cancer.

PMID- 30296874
TI  - Sleep problems and mental health among young Norwegian adolescents.
AB  - PURPOSE: The present study investigated the associations between the aspects of
      sleep problems and mental health in Norwegian young adolescents. MATERIALS AND
      METHODS: Adolescents (12-13 years) were recruited from the primary schools in
      Telemark County, Norway. Sleep related problems were assessed by asking parents
      three questions related to their childrens' sleep quality, sleep sufficiency, and
      daytime sleepiness. Parents reported data on mental health by the extended
      version of the Strengths and Difficulties Questionnaire (SDQ), and information on
      the child's physical activity, screen time, eating pattern, gender, and
      background variables. Height and weight were objectively measured. Complete data
      were obtained for 690 adolescents. RESULTS: Multiple logistic regressions were
      used. Bivariate analyses indicated important associations between the sleep
      aspects and mental health. When adjusting the sleep variables for each other,
      lifestyle factors and background variables, sleep quality problems were
      associated with any psychiatric problem (ORadj: 4.0, CI: 2.0-8.2), emotional
      problems (ORadj: 15.1, CI: 3.4-66.8), and hyperactivity-inattention problems
      (ORadj: 5.1, CI: 2.2-12.1). Daytime sleepiness problems were associated with any
      psychiatric problem (ORadj: 2.3, CI: 1.2-4.4), and hyperactivity-inattention
      problems (ORadj: 2.5, CI: 1.1-5.5). Bivariate associations between problems with
      sufficient sleep and mental health problems lost the significance when adjusted
      for other sleep variables. CONCLUSIONS: The results indicate that different
      aspects of sleep problems may be important underlying factors for mental health
      problems in adolescents, independently of lifestyle factors, BMI-category,
      gender, and background variables. This highlights the importance of examining
      specific sleep problems when investigating associations between sleep and mental
      health.

PMID- 30296875
TI  - Improved Medication Management With Introduction of a Perioperative and
      Prescribing Pharmacist Service.
AB  - BACKGROUND: The medication lists in pre-admission clinic (PAC) questionnaires
      completed by patients prior to surgery are often inaccurate, potentially leading
      to medication errors during hospitalization. Studies have shown pharmacists are
      more accurate when obtaining a medication history and transcribing prescription
      orders, thereby reducing errors. OBJECTIVE: To evaluate the impact of a
      PeRiopErative and Prescribing (PREP) pharmacist on postoperative medication
      management. METHODS: A randomized prospective interventional study enrolled
      elective surgery patients at high risk for medication misadventure to receive
      PREP pharmacy service or usual care (control group). A best possible medication
      history (BPMH) was obtained by the PREP pharmacist and was available to surgical
      staff on admission. The PREP pharmacist also prepared discharge prescriptions for
      their patients. The primary outcomes for the study were accuracy of BPMH and
      discharge prescriptions compared to usual care. The study was powered to 80% with
      2-tailed significance alpha of .05. RESULTS: The medication history in the PREP
      pharmacist group had fewer errors than the control group: 9% (5/53) versus 96%
      (49/51; P < .001). Discharge prescriptions prepared by the PREP pharmacist had
      fewer errors than control group: 25% versus 78% ( P < .001). Significantly, more
      PREP pharmacist patients received a discharge summary with a complete medication
      list: 75% versus 33% ( P = .001). Inpatient prescribing was more accurate in the
      PREP pharmacist patients: 0.64 versus 1.31 errors per patient ( P = .047).
      CONCLUSION: Inclusion of the PREP pharmacist role in the elective surgery
      multidisciplinary team improved the accuracy of medication histories, inpatient
      prescribing, and discharge prescriptions for patients at high risk of medication
      misadventure.

PMID- 30296876
TI  - Can certain factors for recurrence of placenta-mediated pregnancy complications
      be identified after an initial small-for-gestational-age birth?
AB  - OBJECTIVES: After a small-for-gestational-age (SGA) birth, recurrence of placenta
      mediated pregnancy complications (PMPCs) is a cause for anxiety when
      contemplating another pregnancy. We sought to identify factors potentially
      associated with this recurrence. STUDY DESIGN: This retrospective single-center
      observational study was conducted in a tertiary maternity unit between 1 January,
      2010 and 31 December, 2017. We included all women having experienced a non
      syndromic SGA birth and who were subsequently monitored for at least one other
      pregnancy in our institution. PMPCs were defined as recurrent SGA births, three
      consecutive first-trimester miscarriages, or preeclampsia. RESULTS: Ninety-four
      women were included over a 7-year study period. Recurrent PMPCs were recorded in
      30 (32%) cases, of which 29 featured recurrent SGA births. None of the following
      characteristics were significantly associated with recurrence: presence of
      preeclampsia during the initial pregnancy (six [20%] versus 25 [39%] cases in the
      recurrent PMPCs and nonrecurrent PMPCs groups respectively; p = 0.11), results of
      the histopathologic placental examination or thrombophilia screen (positive in 5
      [17%] cases versus 17 [27%] respectively; p = 0.27), or implemented treatment
      during subsequent pregnancies. CONCLUSIONS: PMPCs recur frequently. No risk
      factor for recurrence was identified in our study. Results of etiologic
      assessments and treatments implemented after an initial SGA birth should
      therefore not modify level of clinical and ultrasound monitoring provided during
      subsequent pregnancies.

PMID- 30296877
TI  - Teaching sociology to undergraduate medical students.
AB  - Understanding the social basis of health and medicine and the contexts of
      clinical care are essential components of good medical practice. This includes
      the ways in which social factors such as class, ethnicity, and gender influence
      health outcomes and how people experience health, illness, and health care. In
      our Guide we describe what sociology is and what it brings to medicine, beginning
      with the nature of the "sociological imagination." Sociological theory and
      methods are reviewed to explain and illustrate the role of sociology in the
      context of undergraduate medical education. Reference is made to the 2016 report,
      A Core Curriculum for Sociology in UK Undergraduate Medical Education by Collett
      et al. Teaching and student learning are discussed in terms of organization and
      delivery, with an emphasis on practice. Sections are also included on assessment,
      evaluation, opportunities, and challenges and the value of a "community of
      practice" for sociology teachers in medical education.

PMID- 30296878
TI  - Treatment, transport, and primary care involvement when helicopter emergency
      medical services are inaccessible: a retrospective study.
AB  - OBJECTIVE: To examine handling of cancelled helicopter emergency medical services
      (HEMS) missions with a persisting medical indication. DESIGN: Retrospective
      observational study. SETTING AND SUBJECTS: Cancelled HEMS missions with
      persisting medical indication within Sogn og Fjordane county in Norway during the
      period of 2010-2013. Both primary and secondary missions were included. MAIN
      OUTCOME MEASURES: Primary care involvement, treatment and cooperation within the
      prehospital system. RESULTS: Our analysis included 172 missions with 180
      patients. Two-thirds of the patients (118/180) were from primary missions. In 95%
      (112/118) of primary missions, GPs were alerted, and they examined 62% (70/112)
      of these patients. Among the patients examined by a GP, 30% (21/70) were
      accompanied by a GP during transport to hospital. GP involvement did not differ
      according to time of day (p = 0.601), diagnostic group (p = 0.309), or patient's
      age (p = 0.409). In 41% of primary missions, the patients received no treatment
      or oxygen only during transport. Among the secondary missions, 10% (6/62) of
      patients were intubated or received non-invasive ventilation and were accompanied
      by a physician or nurse anaesthetist during transport. CONCLUSIONS: Ambulance
      workers and GPs have an important role when HEMS is unavailable. Our findings
      indicated good collaboration among the prehospital personnel. Many of the
      patients were provided minimal or no treatment, and treatment did not differ
      according to GP involvement. Key Points Knowledge about handling and involvement
      of prehospital services in cancelled helicopter emergency medical services (HEMS)
      missions are scarce. Ambulance workers and general practitioners have an
      important role when HEMS is unavailable Minimal or no treatment was given to a
      large amount of the patients, regardless of which health personnel who
      encountered the patient.

PMID- 30296879
TI  - Media Use, Sleep Quality, and ADHD Symptoms in a Community Sample and a Sample of
      ADHD Patients Aged 8 to 18 Years.
AB  - OBJECTIVE: Relationships between sleep, screen-based media, and ADHD
      symptomatology were investigated using a case- and community-based approach.
      METHOD: N = 357 healthy and N = 61 children with ADHD (12.72 +/- 2.83 years)
      completed a sleep and media questionnaire. To measure ADHD symptomatology,
      parents filled out the Strengths and Weaknesses of ADHD symptoms and Normal
      behavior (SWAN) scale. Two samples were formed: a matched ( N = 61 patients and N
      = 61 controls) and a community sample ( N = 357 healthy participants and N = 20
      patients). RESULTS: Compared with controls, participants with ADHD reported
      delayed sleep onset and more screen time on school days. Adolescent patients
      showed more behavior promoting delayed sleep phase. In the community sample,
      media time, sleep deviation, and circadian rhythm were correlated with ADHD
      symptomatology. Furthermore, media time, sleep-wake behavior, and sleep deviation
      were predictive of ADHD symptomatology (variance explained = 4%-15%). CONCLUSION:
      Longer media time and inadequate sleep-wake behavior increase the risk of ADHD
      like symptoms. However, research using objective assessments is needed to
      disentangle this distinct association and to provide possible directions for
      intervention.

PMID- 30296881
TI  - Temperament and Cognitive Regulation During the First 3 Years of Life as
      Predictors of Inattention and Hyperactivity/Impulsivity at 6 Years.
AB  - OBJECTIVE: With a wish to identify early markers of inattention and
      hyperactivity/impulsivity, we examined effects of temperament and cognitive
      regulation, during the first 3 years of life, on later inattentive and
      hyperactive/impulsive behavior. METHOD: Temperament and cognitive regulation were
      assessed at 12, 18, 24, and 36 months in 66 typically developing children.
      Teachers rated inattention and hyperactivity/impulsivity at 6 years. RESULTS:
      Temperamental activity at all studied time points was predictive of later
      hyperactive/impulsive behavior, thus appearing as a stable marker thereof.
      Activity at 12 months was also predictive of inattention, whereas temperamental
      persistence was correlated with inattention and hyperactivity/impulsivity, but
      with no independent contributions. No significant relations between cognitive
      regulation and the outcome measures were found. CONCLUSION: Our findings add to
      the scarce literature proposing that markers of inattentive and
      hyperactive/impulsive behavior in early school age can be found within the first
      years of life, using parental ratings of child temperament.

PMID- 30296880
TI  - Effects of angiotensin-converting enzyme inhibitors and angiotensin receptor
      blockers on cardiovascular events in patients with diabetes and overt
      nephropathy: a meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: The efficacy of angiotensin-converting enzyme inhibitors and
      angiotensin receptor blockers in reducing cardiovascular outcomes in patients
      with diabetes and overt nephropathy is still a controversial issue. METHODS: We
      systematically searched MEDLINE, Embase and Cochrane Library for randomised
      controlled trials. RESULTS: Thirteen trials containing 4638 patients with
      diabetes and overt nephropathy were included. Compared with controls, angiotensin
      converting enzyme inhibitor/angiotensin receptor blocker treatment did not reduce
      the risk of cardiovascular events (odds ratio 0.94, 95% confidence interval 0.86
      to 1.03, P=0.18; I2=0.0%, P=0.75). Angiotensin-converting enzyme
      inhibitor/angiotensin receptor blocker therapy reduced the odds of heart failure
      events by 29% (0.71, 0.61 to 0.83, P<0.001; I2=0%, P=0.78). The results indicated
      no significant differences between the two treatment regimens with regard to the
      frequency of MI (0.95, 0.76 to 1.19, P=0.64), stroke (1.20, 0.83 to 1.74,
      P=0.32), cardiovascular death (1.26, 0.96 to 1.65, P=0.09) and all-cause
      mortality (0.98, 0.86 to 1.12, P=0.73). Among all kinds of adverse effects,
      angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy
      increased the incidence of hyperkalemia (2.26, 1.42 to 3.61, P=0.001).
      CONCLUSION: This study demonstrated that angiotensin-converting enzyme inhibitors
      and angiotensin receptor blockers did not reduce cardiovascular events in
      patients with diabetes and overt nephropathy.

PMID- 30296882
TI  - Healthy Volunteers' Perceptions of the Benefits of Their Participation in Phase I
      Clinical Trials.
AB  - Other than the financial motivations for enrolling in Phase I trials, research on
      how healthy volunteers perceive the benefits of their trial participation is
      scant. Using qualitative interviews conducted with 178 U.S. healthy volunteers
      enrolled in Phase I trials, we investigated how participants described the
      benefits of their study involvement, including, but not limited to, the financial
      compensation, and we analyzed how these perceptions varied based on participants'
      sociodemographic characteristics and clinical trial history. We found that
      participants detailed economic, societal, and noneconomic personal benefits. We
      also found differences in participants' perceived benefits based on gender, age,
      ethnicity, educational attainment, employment status, and number of clinical
      trials completed. Our study indicates that many healthy volunteers believe they
      gain more than just the financial compensation when they accept the risks of
      Phase I participation.

PMID- 30296883
TI  - The Relationship Between Executive Function Deficits and DSM-5-Defined ADHD
      Symptoms.
AB  - OBJECTIVES: To identify the relationship between the core Diagnostic and
      Statistical Manual of Mental Disorders (5th ed.) ADHD symptoms and executive
      function deficits (EFDs), to evaluate ADHD characteristics of those with
      executive dysfunction (ED), and to examine the predictive utility of the Adult
      ADHD Investigator Symptom Rating Scale (AISRS) in identifying those with adult
      ADHD and ED. METHOD: Two samples (referred and primary care practice) were pooled
      together for present analysis. RESULTS: Final analysis included 297 respondents,
      171 with adult ADHD. Spearman correlation coefficients and binary logistic
      regressions demonstrated that ADHD inattentive (IA) and hyperactive-impulsive (H
      I) symptoms were moderately to strongly correlated with and highly predictive of
      EFDs. Receiver operating characteristic curve analysis showed that an AISRS DSM
      18-item score of ? 28 was most predictive of clinical ED. CONCLUSION: ADHD
      symptoms were strongly correlated with and predictive of EFDs, clinicians should
      screen adults with ADHD for EFDs and ADHD treatment providers should track EFD
      improvement in addition to DSM-5 ADHD symptoms.

PMID- 30296884
TI  - Measuring the Quality and Performance of Institutional Review Boards.
AB  - Despite the importance of institutional review boards (IRBs) in protecting human
      subjects participating in research and the well-known benefits of performance
      measurements, there has been no systematic assessment of the quality and
      performance of IRBs. The IRB community has frequently cited the lack of credible
      metrics for measuring human subject protections and the quality of IRB ethics
      reviews as reasons for not measuring the quality and performance of IRBs.
      However, the IRB, with its well-defined missions, functions, structure, and
      procedures, should be readily amendable to performance measurements. In this
      brief commentary, I analyzed potential barriers for measuring the quality of IRBs
      and proposed ways to overcome these barriers.

PMID- 30296885
TI  - Quality assessment in general practice: diagnosis and antibiotic treatment of
      acute respiratory tract infections.
AB  - OBJECTIVE: To investigate areas in need of quality improvement within the
      diagnostic process and antibiotic treatment of acute respiratory tract infections
      (RTIs) in Danish general practice by using quality indicators (QIs). DESIGN AND
      SETTING: During a 4-week period in winter 2017, a prospective registration of
      patients diagnosed with RTIs was conducted in general practice in two regions of
      Denmark. SUBJECTS: Throughout the registration period each patient with symptoms
      of an RTI was registered. Information about age, symptoms and findings, duration
      of symptoms, the use and result of clinical tests, allergy towards penicillin,
      referral to secondary care and the antibiotic given were recorded. MAIN OUTCOME
      MEASURES: Values and acceptable ranges for QIs focusing on the diagnostic
      process, the decision to prescribe antibiotics and the choice of antibiotics for
      patients with RTIs. RESULTS: Regarding the diagnostic process nearly all QIs for
      patients diagnosed with acute pharyngotonsillitis and pneumonia fell within the
      acceptable range. Contrarily, the diagnostic QIs for patients with acute otitis
      media and acute rhinosinusitis were outside the acceptable range. All indicators
      designed to measure overuse of antibiotics were outside the acceptable range and
      nearly all indicators assessing if patients were sufficiently treated fell within
      the acceptable range. QIs assessing use of the recommended type of antibiotic
      were only within the acceptable range for patients diagnosed with acute
      pharyngotonsillitis. CONCLUSION: The findings indicate an overuse of antibiotics
      for RTIs in Danish general practice. Especially management of acute
      rhinosinusitis and acute bronchitis should be targeted in future quality
      improvement projects. KEY POINTS: To improve antibiotic prescribing in general
      practice it is important to focus on both the diagnostic process and the
      prescribing patterns. The findings indicate an overuse of antibiotics for acute
      respiratory tract infections in Danish general practice. Especially the
      diagnostic process and antibiotic prescribing patterns for acute rhinosinusitis
      and acute bronchitis could benefit from future quality improvement interventions.

PMID- 30296886
TI  - Educational Attainment and Perceived Need for Urgent Care.
AB  - While lower educational attainment is associated with worse health status,
      education may also affect one's ability to identify need for urgent care. Using
      data from the 2010 Medicare CAHPS survey, we estimated multivariate logistic
      models to test the relationship between self-reported educational attainment and
      the perceived need for urgent care, controlling for health status and other
      factors. As expected, lower educational attainment was associated with greater
      reported need for urgent care in bivariate analyses because of poorer health.
      However, lower educational attainment was associated with less perceived need for
      urgent care after controlling for health status, particularly for those in poor
      health. These findings suggest the need for interventions to improve the
      likelihood that people with less education recognize the need for urgent care,
      particularly those in poor health and in most need of urgent care.

PMID- 30296887
TI  - Short-term Outcome of Straight vs Tapered Carotid Stenting for Symptomatic
      Carotid Artery Stenosis: A Prospective Study.
AB  - PURPOSE: To investigate the short-term outcomes and complications of straight vs
      tapered carotid stent placement for patients with symptomatic carotid stenosis.
      METHODS: A prospective study was conducted to examine if tapered carotid stents
      (TCS) performed better than straight carotid stents (SCS) in terms of
      complications and outcomes in patients with a unilateral, symptomatic, internal
      carotid artery stenosis ?70%. Between January 2014 and January 2016, 236 patients
      were screened; 88 were excluded, leaving 148 patients for 1:1 randomization to
      carotid artery stenting with either SCS or TCS. The data were analyzed for
      differences between the groups in terms of complications (hemodynamic depression,
      cerebral hyperperfusion syndrome, puncture site sequelae) and endpoint events
      (stroke, myocardial infarction, and death) at 30 days and 6 months. RESULTS: Two
      patients in the TCS group underwent endarterectomy after allocation, leaving 72
      patients (mean age 65.1+/-8.8 years; 59 men) in the TCS group for analysis vs 74
      (mean age 65.0+/-7.9 years; 58 men) in the SCS group. The technical success was
      100% in both groups. The incidence of hemodynamic depression (hypotension and
      bradycardia) after the procedures were higher in the SCS group (p=0.04), and the
      patients who underwent SCS procedures had longer hospital stays (p=0.01). There
      was no difference in the incidences of complications, myocardial infarction,
      mortality, or stroke at 30 days or 6 months between the SCS and TCS groups. The
      rates of restenosis (4% SCS vs 1% TCS) were similar (p=0.63); all restenoses were
      moderate (50%-70%). CONCLUSION: When compared to straight stents, tapered carotid
      stents significantly decreased hemodynamic complications and hospital stay.

PMID- 30296888
TI  - Tapered Carotid Stents: An Essential Modification to Improve Carotid Artery
      Stenting Outcomes?

PMID- 30296889
TI  - Does short-term weekly teriparatide improve healing in unstable intertrochanteric
      fractures?
AB  - : Slow recovery after hip fracture has been associated with negative
      consequences. Thus, there is medical need to improve healing and functional
      recovery after intertrochanteric fracture. The aim of this study was to measure
      whether short-term teriparatide would improve healing in intertrochanteric
      fractures after internal fixation as measured by (1) clinical scores, (2)
      radiographic fracture healing, and (3) complication rates. We retrospectively
      reviewed 96 patients (average age, 82 years) who underwent closed reduction and
      internal fixation with proximal femoral nail (PFN) for unstable intertrochanteric
      fractures between 2014 and 2016. Of the 96 patients, 56 patients were treated
      with a PFN alone (group 1). These patients were compared with 46 patients for
      whom the same device was used and a weekly subcutaneous injection of PTH 1-34
      (teriparatide) was prescribed postoperatively (group 2). Questionnaire surveys or
      telephone interviews were conducted, and patients completed a self-report Harris
      hip score and visual analog scale scores. The radiological time to fracture
      healing was assessed as the primary end point. Postoperative complication rates
      were compared. Functional outcomes at 6 months after surgery were similar in both
      groups. There were no differences between groups in the proportion of patients
      achieving radiographic fracture healing. The frequency of patients reporting
      adverse events was 20% (10 of 50) in group 1 versus 17% (8 of 46) in group 2 ( p
      = 0.744). Short-term teriparatide did not improve radiographic signs of fracture
      healing of an intertrochanteric fracture and reduce the incidence of
      complications. The effect of teriparatide on fracture healing remains uncertain.
      Further multicenter prospective studies are needed to demonstrate objective long
      term results of parathyroid hormone therapy in patient with hip fracture. LEVEL
      OF EVIDENCE: Level IV, therapeutic study.

PMID- 30296890
TI  - Posterior Inferior Turbinate Hypertrophy (PITH).
AB  - Hypertrophy of the soft tissue of the posterior inferior turbinate (PITH) may be
      observed during nasal endoscopy, although the clinical significance is not
      understood. We report a cross-sectional study of consecutive new patients
      undergoing baseline nasal endoscopy in a tertiary rhinology clinic. Subjects
      completed 22-Item Sinonasal Outcome Test (SNOT-22) and Nasal Obstruction Symptom
      Evaluation (NOSE) questionnaires. Of 391 subjects screened, PITH was present in
      62 (15.9%), with a female predominance. The prevalence of allergic rhinitis and
      chronic rhinosinusitis was comparable between PITH and non-PITH groups.
      Nonpurulent exudate flowing from the posterior inferior turbinate into the
      nasopharynx was more prevalent in association with PITH (83.9% vs 14.3%, P <
      .001). Mean SNOT-22 scores and NOSE scores were not significantly different
      between PITH and non-PITH groups. This preliminary study suggests that PITH is a
      common physical finding with unclear etiology and should be the subject of
      further investigation.

PMID- 30296891
TI  - A third HSAN5 mutation disrupts the nerve growth factor furin cleavage site.
AB  - Bi-allelic dysfunctional mutations in nerve growth factor (NGF) cause the rare
      human phenotype hereditary sensory and autonomic neuropathy type 5 (HSAN5). We
      describe a novel NGF mutation in an individual with typical HSAN5 findings. The
      mutation c.361C>T, p.R121W is at the last residue of the furin cleavage motif Arg
      Ser-Lys-Arg in proNGF. We show that the p.R121W mutation completely abolishes the
      formation of mature NGF-beta. Surprisingly, mutant p.R121W cells produced very
      little proNGF. Instead, the two progressive cleavage products of proNGF were
      produced, proA-NGF and proB-NGF, with proB-NGF being the predominant NGF-derived
      peptide and the only peptide secreted by mutant p.R121W cells. We found that the
      ability of the p.R121W mutation to cause tropomyosin receptor kinase A
      autophosphorylation and mitogen-activated protein kinase phosphorylation was
      significantly reduced compared to controls (p < 0.05 and p < 0.01). By studying
      the PC12 cell line morphology and neurite length over a week, we found the
      p.R121W mutation had residual, but much reduced, neurotrophic activity when
      compared to wild-type NGF. Finally, we assessed whether the p.R121W mutation
      affected apoptosis and found a reduced protective effect compared to wild-type
      NGF. Our results suggest that the p.R121W NGF mutation causes HSAN5 through
      negating the ability of furin to cleave proNGF to produce NGF-beta.

PMID- 30296892
TI  - Informing efficient pilot development of animal trauma models through quality
      improvement strategies.
AB  - Poor quality data in preclinical trials can result from inconsistent and
      unstandardized experimental processes. Unpredictable pre-intervention variability
      generates unreliable data, biases outcomes and results in needless waste of
      animals and resources. We applied Define-Measure-Analyse-Improve-Control (DMAIC)
      quality improvement processes to pilot development of a swine model of trauma,
      haemorrhagic shock and coagulopathy. The goal was to reduce variability through
      protocol standardization and error reduction. Six male Sinclair swine were
      sequentially anesthetized, intubated, mechanically ventilated and instrumented,
      then subjected to multiple-hit injury, followed by fluid resuscitation monitoring
      and coagulation testing. Experimental tasks were defined and mapped. Performance
      measures were task performance times, subject stabilization time and number of
      task execution errors. Process improvement was assessed by reduced times and
      errors, and subject stability at target physiological values. Previously
      overlooked performance errors and deficiencies were identified. 'Mistake
      proofing' actions included personnel retraining, revisions of standard operating
      procedures and use of checklists. The quality improvement pilot trial produced a
      stable model with reduced protocol deviations. Data quality can be improved and
      animal waste minimized, if experimental planning incorporates strategies to
      ensure protocol adherence and reduced operator performance variation and errors.
      Properly designed pilot trials can be essential components of refinement and
      reduction strategies in animal-based research.

PMID- 30296893
TI  - Intraductal Pneumatic Lithotripsy after Extended Transoral Duct Surgery in
      Submandibular Sialolithiasis.
AB  - Objective Persistent, residual, or recurrent stones after transoral duct surgery
      are always associated with hilar to intraparenchymal and/or multiple
      sialolithiasis, causing difficulties in the treatment. This study was performed
      to assess the value of intraductal lithotripsy in the treatment of persistent,
      residual, or recurrent sialolithiasis after extended duct surgery in the
      submandibular gland. Study Design Retrospective study covering February 2015 to
      June 2018. Study Setting Tertiary referral center for salivary gland diseases.
      Subjects and Methods After extended ductal surgery, 39 patients presenting with
      persistent, residual, or recurrent stones were treated. Four patients had
      persistent stones; 16 had residual stones; and 19 presented with recurrent
      stones. Among these patients, 50 stones were treated with intraductal pneumatic
      lithotripsy. Fragmentation rate, stone-free rate, and symptom-free rate after
      treatment with intraductal lithotripsy were outcome measures. Results Of the 39
      patients, 97.4% became stone-free, and all were symptom-free. Ninety-eight
      percent of the stones were completely fragmented. For 23.1% of the patients, >1
      stone was treated with intraductal lithotripsy. All patients with persistent
      stones, 93.7% of those with residual stones, and all with recurrent stones became
      stone-free and symptom-free. No severe complications developed. Conclusions This
      study shows that patients presenting with difficult and/or multiple
      sialolithiasis after extended transoral submandibular duct surgery can be treated
      with success rates >97%. For multiple sialolithiasis in particular, a multimodal
      treatment approach with interventional sialendoscopy and intraductal lithotripsy
      as a central element is a prerequisite for success, as this enables the most
      difficult part to be performed with high success rates.

PMID- 30296894
TI  - Neuropsychological predictors of patient-reported cognitive decline after deep
      brain stimulation in Parkinson's disease.
AB  - BACKGROUND: Deep brain stimulation (DBS) is effective for treatment of motor
      complications of dopaminergic therapy in Parkinson's disease (PD) but
      occasionally has been associated with multidomain cognitive decline. Patient- and
      caregiver-reported cognitive decline are clinically meaningful and increasingly
      recognized as important to consider when evaluating therapeutic interventions for
      PD. OBJECTIVE: The objective was to assess presurgical neuropsychological and
      clinical factors associated with PD patient- and caregiver-reported cognitive
      decline in two or more domains after DBS. METHOD: A single telephone survey was
      used to assess patient- and caregiver-reported cognitive decline in five domains
      at both one and four months after DBS surgery. Decline in two or more domains was
      considered multidomain cognitive decline (MDCD). Baseline demographic, clinical,
      and neuropsychological factors were compared in those with or without MDCD.
      Preoperative neuropsychological measures were evaluated as risk factors and
      regressed on the presence of MDCD, with demographic covariates, using multiple
      logistic regression. RESULTS: Preoperative performance in verbal recognition
      memory, language knowledge, and verbal processing decline were associated with
      postoperative, patient-reported MDCD in the first four weeks. MDCD at four months
      after DBS was associated with worse preoperative verbal reasoning, verbal recall,
      and semantic verbal fluency. Caregiver-reported MDCD one month after DBS was
      associated with poorer baseline verbal memory recognition
      accuracy/discriminability, visuospatial problem solving, and constructional
      praxis. CONCLUSION: Poor presurgical performance in verbal memory recognition,
      language processing, and visuospatial performance is associated with patient- or
      caregiver-reported decline following DBS surgery. Posterior cortical dysfunction
      seems to portend significant self-reported cognitive decline following deep brain
      stimulation.

PMID- 30296895
TI  - Drug Targets for Heart Failure with Preserved Ejection Fraction: A Mechanistic
      Approach and Review of Contemporary Clinical Trials.
AB  - Heart failure with preserved ejection fraction (HFpEF) accounts for over half of
      prevalent heart failure (HF) worldwide, and prognosis after hospitalization for
      HFpEF remains poor. Due, at least in part, to the heterogeneous nature of HFpEF,
      drug development has proved immensely challenging. Currently, there are no
      universally accepted therapies that alter the clinical course of HFpEF. Despite
      these challenges, important mechanistic understandings of the disease have
      revealed that the pathophysiology of HFpEF is distinct from that of HF with
      reduced ejection fraction and have also highlighted potential new therapeutic
      targets for HFpEF. Of note, HFpEF is a systemic syndrome affecting multiple organ
      systems. Depending on the organ systems involved, certain novel therapies offer
      promise in reducing the morbidity of the HFpEF syndrome. In this review, we aim
      to discuss novel pharmacotherapies for HFpEF based on its unique pathophysiology
      and identify key research strategies to further elucidate mechanistic pathways to
      develop novel therapeutics in the future. Expected final online publication date
      for the Annual Review of Pharmacology and Toxicology Volume 59 is January 6,
      2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised
      estimates.

PMID- 30296896
TI  - Molecular Pharmacology and Neurobiology of Rapid-Acting Antidepressants.
AB  - For decades, symptoms of depression have been treated primarily with medications
      that target the monoaminergic brain systems, which typically take weeks to exert
      measurable effects and months to exert remission of symptoms. Low, subanesthetic
      doses of (R,S)-ketamine (ketamine) result in the rapid improvement of core
      depressive symptoms, including mood, anhedonia, and suicidal ideation, occurring
      within hours following a single administration, with relief from symptoms
      typically lasting up to a week. The discovery of these actions of ketamine has
      resulted in a reconceptualization of how depression could be more effectively
      treated in the future. In this review, we discuss clinical data pertaining to
      ketamine and other rapidacting antidepressant drugs, as well as the current state
      of pharmacological knowledge regarding their mechanism of action. Additionally,
      we discuss the neurobiological circuits that are engaged by this drug class and
      that may be targeted by a future generation of medications, for example,
      hydroxynorketamine; metabotropic glutamate receptor 2/3 antagonists; and N-methyl
      Daspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and gamma
      aminobutyric acid receptor modulators. Expected final online publication date for
      the Annual Review of Pharmacology and Toxicology Volume 59 is January 6, 2019.
      Please see http://www.annualreviews.org/page/journal/pubdates for revised
      estimates.

PMID- 30296897
TI  - Cardiovascular Pharmacogenomics: Does It Matter If You're Black or White?
AB  - Race and ancestry have long been associated with differential risk and outcomes
      to disease as well as responses to medications. These differences in drug
      response are multifactorial with some portion associated with genomic variation.
      The field of pharmacogenomics aims to predict drug response in patients prior to
      medication administration and to uncover the biological underpinnings of drug
      response. The field of human genetics has long recognized that genetic variation
      differs in frequency between ancestral populations, with some single nucleotide
      polymorphisms found solely in one population. Thus far, most pharmacogenomic
      studies have focused on individuals of European and East Asian ancestry,
      resulting in a substantial disparity in the clinical utility of genetic
      prediction for drug response in US minority populations. In this review, we
      discuss the genetic factors that underlie variability to drug response and known
      pharmacogenomic associations and how these differ between populations, with an
      emphasis on the current knowledge in cardiovascular pharmacogenomics. Expected
      final online publication date for the Annual Review of Pharmacology and
      Toxicology Volume 59 is January 6, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30296898
TI  - Impact of a Clinical Trial in Two District Hospitals in Ghana: Perspectives of
      Ghanaian Researchers.
AB  - Conducting clinical trials in resource-poor settings may contribute to local
      capacity building. We describe the perspectives of local research personnel
      regarding the impact of collaborating in a clinical trial in rural Ghana. Forty
      six Ghanaian research personnel were eligible to complete an anonymous survey,
      and 35 (76%) participated. Of the 35 respondents, 32 (91%) agreed that future
      patients will benefit because the hospital was part of the study. All 35
      respondents reported a personal benefit derived from study involvement, most
      commonly citing skills or knowledge gained. Of the 35 individuals, 21 reported
      one or more burdens, most commonly citing nonspecific research responsibilities.
      Our data support the hypothesis that participation in clinical trials can
      contribute to capacity building in district hospitals in a lower middle-income
      country.

PMID- 30296899
TI  - MAP1A/BLC3? Now I am really confused.
AB  - I routinely see people use incorrect names for MAP1LC3/LC3 isoforms in scientific
      papers. In fact, it happens often enough that I decided to investigate the reason
      for the apparent confusion. It turns out that the sources of misinformation are
      abundant, including UniProt and antibody supplier web sites.

PMID- 30296900
TI  - Innovations in Ventricular Assist Devices for End-Stage Heart Failure.
AB  - The number of patients with end-stage heart failure (HF) continues to increase
      over time, but there has been little change in the availability of organs for
      cardiac transplantation, intensifying the demand for left ventricular assist
      devices (LVADs) as a bridge to transplantation. There is also a growing number of
      patients with end-stage HF who are not transplant candidates but may be eligible
      for long-term support with an LVAD, known as destination therapy. Due to this
      increasing demand, LVAD technology has evolved, resulting in transformative
      improvements in outcomes. Additionally, with growing clinical experience patient
      management continues to be refined, leading to iterative improvements in
      outcomes. With outcomes continuing to improve, the potential benefit from LVAD
      therapy is being considered for patients earlier in their course of advanced HF.
      We review recent changes in technology, patient management, and implant decision
      making in LVAD therapy. Expected final online publication date for the Annual
      Review of Medicine Volume 70 is January 27, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30296902
TI  - Survival Outcomes for Induction vs Adjuvant Chemotherapy in Squamous Cell
      Carcinoma of the Maxillary Sinus.
AB  - Objective In advanced maxillary sinus cancers treated with surgery and
      radiotherapy, poor local control rates and the potential for organ preservation
      have prompted interest in the use of systemic therapy. Our objective was to
      present outcomes for induction compared to adjuvant chemotherapy in the maxillary
      sinus. Study Design Secondary database analysis. Setting National Cancer Database
      (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus
      cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012
      were identified from the NCDB and stratified into induction chemotherapy and
      adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by
      log-rank test, and multivariate Cox regression was performed to evaluate overall
      survival when adjusting for other prognostic factors. Propensity score matching
      was also used for further comparison. Results Twenty-three patients received
      induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log
      rank test comparing induction to adjuvant chemotherapy was not significant ( P =
      .076). In multivariate Cox regression when adjusting for age, sex, race,
      comorbidity, grade, insurance, and T/N stage, there was a significant mortality
      hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence
      interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was
      associated with improved overall survival in comparison to adjuvant chemotherapy
      in a relatively small cohort of patients (in whom treatment choice cannot be
      characterized), suggesting that this question warrants further investigation in a
      controlled clinical trial before any recommendations are made.

PMID- 30296901
TI  - Systematic Review of Supraclavicular Artery Island Flap vs Free Flap in Head and
      Neck Reconstruction.
AB  - Objective The aim of this systematic review is to compare the surgical outcomes
      of supraclavicular artery island flap (SCAIF) and free tissue transfer (FTT) in
      head and neck reconstruction. Data Sources PubMed, Web of Science, and EMBASE
      databases. Review Methods Independent screening and data extraction were
      performed by 2 authors. Only studies that directly compared SCAIF and FTT were
      included. Data were pooled with random-effects meta-analysis to determine the
      standardized mean differences (SMDs), risk differences, and 95% confidence
      intervals (CIs). Heterogeneity was assessed using the I2 statistics. The
      Methodological Index for Non-Randomized Studies tool was used to evaluate extent
      of bias in studies. Results The initial query yielded 661 results, of which 4
      comparative studies remained for final analysis. The pooled sample sizes for the
      SCAIF and FTT cohorts were 100 and 84, respectively. SCAIF was associated with
      reduction of operative time by a large effect size (SMD, 1.65; 95% confidence
      interval, 0.78-2.52). The harvested flap areas and perioperative complications,
      including rates of total flap loss, partial flap necrosis, and recipient/donor
      site dehiscences, were comparable between the 2 procedures with low to high
      heterogeneity among studies. Conclusion SCAIF requires less operative time and
      has comparable short-term perioperative results to FTT. The findings of this
      study support the viability of SCAIF as an alternative to FTT and provide
      evidence for its inclusion in the reconstructive armamentarium of major head and
      neck ablation and trauma.

PMID- 30296903
TI  - Prevalence of vitamin D deficiency in Iran: A systematic review and meta
      analysis.
AB  - BACKGROUND: The prevalence of vitamin D deficiency in the Iranian community is
      very high. Women and older people are at the higher risk of vitamin D deficiency.
      AIM: This study aimed to estimate the prevalence of vitamin D deficiency in Iran
      by combining the results of various studies. METHODS: This was a systematic
      review and meta-analysis. Separate strategies were developed for search in
      national databases (Irandoc, Magiran, SID) and international databases (Web of
      Science, PubMed, and Scopus) using the keywords of "vitamin D deficiency,"
      "Iran," and "prevalence." The titles and abstracts of the articles were screened
      and related full texts were appraised. Those articles that met inclusion criteria
      were selected for meta-analysis. The heterogeneity of the articles was assessed
      via the Chi-square test. They were combined using the random-effect approach. In
      addition, the groups were categorized and analyzed in terms of age and gender.
      RESULTS: Of 639 articles, 30 articles with a sample size of 26,042 people were
      included for data analysis. The overall prevalence of vitamin D deficiency was
      reported as 0.56. Subgroup analysis showed that 0.64 of women and 0.44 of men
      were suffering from vitamin D deficiency. The prevalence of vitamin D deficiency
      in the age groups under 20, 20-50, and over 50 years was 0.56.4, 0.72.4, and
      0.59.8, respectively. CONCLUSIONS: The Iranian Ministry of Health is expected to
      design strategies to improve the status of vitamin D at the national level.

PMID- 30296905
TI  - Gross Pathology of Routine Pediatric Tonsillectomy Specimens: Optimizing the
      Value of Patient Care.
AB  - Objective This investigation seeks to evaluate the effect of gross pathologic
      analysis on our management of patients undergoing routine tonsillectomy and to
      evaluate charges and reimbursement. Study Design Retrospective chart review from
      2005 through 2016. Setting Academic medical center. Subjects and Methods
      Participants were pediatric patients aged 14 years and younger undergoing
      tonsillectomy for either sleep-disordered breathing or tonsillitis, with
      tonsillectomy specimens evaluated by pathology, and without any risk factors for
      pediatric malignancy. Records were reviewed for demographics, surgical
      indications, and pathology. Abnormal reports prompted an in-depth review of the
      chart. Charges and reimbursement related to both hospital and professional fees
      for gross tonsil analysis were evaluated. Results From 2005 to 2016, 3183 routine
      pediatric tonsillectomy cases were performed with corresponding specimens that
      were sent for gross analysis revealing no significant pathologic findings; 1841
      were males and 1342 were females. Ten cases underwent microscopy by pathologist
      order, revealing normal tonsillar tissue. The mean charge per patient for gross
      analysis was $60.67 if tonsils were together as 1 specimen and $77.67 if tonsils
      were sent as 2 separate specimens; respective reimbursement amounts were $28.74
      and $35.90. Conclusions Gross pathologic analysis did not change our management
      of routine pediatric tonsillectomy patients. Foregoing the practice at our
      institution would eliminate $19,171.72 to $24,543.72 in charges and $9081.40 to
      $11,344.40 in reimbursement per year. Eliminating this test would improve the
      value of patient care by saving health care resources without compromising
      clinical outcomes.

PMID- 30296904
TI  - Psychosocial functioning following moderate-to-severe pediatric traumatic brain
      injury: recommended outcome instruments for research and remediation studies.
AB  - Psychosocial functioning is compromised following pediatric traumatic brain
      injury (TBI), with the past few decades witnessing a proliferation of research
      examining the effect of childhood brain insult on a range of psychosocial
      outcomes. This paper describes the systematic recommendation of outcome
      instruments to address psychosocial functioning following pediatric TBI. A total
      of 65 instruments across 11 psychosocial areas (i.e., Global Outcome,
      Communication, Social Cognition, Behavioural and Executive Function, Other
      Neuropsychological Functioning, Psychological Status, TBI-related Symptoms,
      Activities and Participation, Support and Relationships, Sense of Self, and
      Health-Related Quality of Life) were reviewed using various assessment methods,
      including working groups, literature searches, comparisons with selection
      guidelines, and international expert opinion. Each measure was reviewed for its
      usefulness across early recovery, intervention, and outcome related studies. 34
      instruments were recommended and classified according to the World Health
      Organization's International Classification of Functioning, Disability and Health
      taxonomy and categorised by psychosocial area. This compilation provides a common
      framework to guide the activities of clinicians and researchers in psychosocial
      rehabilitation. It is anticipated that these will foster a multidisciplinary
      approach to psychosocial dysfunction to enhance the evaluation, prediction, and
      improvement of functional outcomes for those with pediatric TBI.

PMID- 30296906
TI  - Geographic and Racial Disparities in Infant Hearing Loss.
AB  - Objective Approximately 1 to 2 of every 1000 American newborns has hearing loss
      identified by newborn screening. This study was designed to determine if infant
      hearing loss is more common in socioeconomically disadvantaged communities. Study
      Design In this retrospective study, we analyzed electronic medical record data
      using geostatistical models. Setting Infants were residents of Durham County,
      North Carolina, born in 2 hospitals of the Duke University Health System. This
      county includes the city of Durham and surrounding suburban and rural
      communities. Subjects and Methods Subjects were hearing-screened newborns, born
      between 2005 and 2016, whose residential address was in Durham County, North
      Carolina. This was a retrospective study using medical record data. We used
      Bayesian regression models with smoothing of coordinate date to identify both
      spatial and nonspatial predictors of infant hearing loss. Results We identified
      19,348 infants from Durham County, of whom 675 had failed initial hearing
      screening and 191 had hearing loss confirmed on follow-up. Hearing loss was
      significantly associated with minority race (odds ratio [OR], 2.45; 95%
      confidence interval, 1.97-3.06), as well as lower gestational age and maternal
      sexually transmitted infections. We identified significant geographic
      heterogeneity, with a higher probability of hearing loss in poorer urban
      neighborhoods (local OR range, 0.59-1.39). Neighborhood disadvantage was a
      significant predictor of hearing loss, as was high local seroprevalence of
      cytomegalovirus (CMV) among pregnant women. Conclusions Urban, low-income
      neighborhoods have a high prevalence of infant hearing loss compared with more
      affluent surrounding communities, particularly among minorities. This
      distribution may be attributable to congenital CMV infection.

PMID- 30296907
TI  - Arterial Switch Operation in a Patient With Ehlers-Danlos Syndrome Type IV.
AB  - Ehlers-Danlos syndrome vascular type IV is characterized by translucent skin,
      easy bruising, and fragility of arteries. A full-term female infant presented at
      four weeks of age with a diagnosis of d-transposition of the great arteries with
      restrictive atrial septal defect. She successfully underwent emergent balloon
      atrial septostomy and placement of patent ductus arteriosus (PDA) stent. She
      required restenting of the PDA and pulmonary artery banding prior to arterial
      switch procedure. At 16 months of age, the patient successfully underwent
      arterial switch procedure without complication. This report demonstrates the
      feasibility of an arterial switch operation along with long-term follow-up of
      this rare condition.

PMID- 30296908
TI  - "Neither a wife nor a widow": an interpretative phenomenological analysis of the
      experiences of female family caregivers in disorders of consciousness.
AB  - Disorders of consciousness (DoC) disrupt close relationships. This study
      investigated the experience of a DoC in the family. Four main themes were
      identified from semi-structured interviews with nine females and analysed using
      Interpretative Phenomenological Analysis (IPA): (1) Loss without a name, (2)
      Relationship without a title, (3) Symbiotic relating and (4) Frozen futures.
      Participants' accounts showed complex losses and relationship transformations
      that were challenging to cope with. Participants embodied the person and
      experienced reductions in rehabilitation and social visits as personally
      abandoning and led to strong advocacy with professionals. The uncertainty created
      by the DoC meant participants lived in the present moment and struggled to make
      plans for their future. Psychological support to demonstrate a sensitivity and
      validation of this unique complex loss, a framework for naming the loss,
      provision of education about the condition and enhancing coping with a chronic
      situation are needed.

PMID- 30296909
TI  - Motivational-general arousal imagery does not improve decision-making performance
      in elite endurance cyclists.
AB  - Emotions are predicted to influence judgement and decision-making across a range
      of performance contexts. This experiment tested whether motivational-general
      arousal imagery can improve the decision-making performance of elite endurance
      cyclists. In total, 54 cyclists (38 men, 16 women) were assigned to either a
      positive imagery condition (where positive images associated with the affective
      experience of winning were encouraged) or a negative imagery condition (where
      negative images associated with poor performance were encouraged). The cyclists
      were read one of two scripts designed to elicit positive or negative images
      during a 20-min maximal sustainable interval on a cycle ergometer. A decision
      making task (colour-word match Stroop) was performed before and immediately after
      the maximal sustainable power interval. Results showed that the manipulation was
      successful with cyclists in the positive imagery condition reporting more
      positive affective states (higher levels of happiness and lower levels of
      dejection) than those in the negative imagery condition. However, there was no
      significant difference between the two groups in their decision-making
      performance under physiological duress. These findings indicate that while
      motivational-general arousal imagery might be a useful method to induce positive
      emotions during exercise, it is unlikely to improve the decision-making
      performance of cyclists in performance-relevant conditions.

PMID- 30296910
TI  - Mitochondrial DNA Copy Number in Peripheral Blood in the First Trimester of
      Pregnancy and Different Preeclampsia Clinical Phenotypes Development: A Pilot
      Study.
AB  - Inflammation and oxidative stress are intrinsically linked to early poor
      placentation, typical of pregnancies complicated by preeclampsia associated with
      intrauterine growth restriction (PE-IUGR). Low mitochondrial DNA copy number
      (mtDNAcn) in peripheral blood constitutes a good peripheral surrogate marker of
      inflammation and oxidative stress. On these basis, we explored a possible
      correlation between mtDNAcn in peripheral blood in the first trimester of
      pregnancy and the PE-IUGR onset. To shed light on this issue, we setup a nested
      case-control study from a prospective cohort of pregnant women undergoing first
      trimester aneuploidies screening. Two groups of patients affected by PE
      classified according to the clinical phenotype were identified: (1) patients who
      developed PE-IUGR and (2) patients who developed PE associated with appropriate
      for gestational age intrauterine fetal growth (PE-AGAf). Controls were women with
      a physiologic pregnancy matched to cases on the basis of age (+/-6 months, ratio
      2:1). Mitochondrial DNA copy number was quantified using real-time polymerase
      chain reaction and normalized to nuclear DNA. The median (interquartile range)
      mtDNAcn in peripheral blood in patients with PE-IUGR (n = 12) and in patients
      with PE-AGAf (n = 16) was 70 (44-97) and 108 (95-145), respectively ( P = .004).
      Both these values were significantly lower than that detected in the control
      group (161[133-183], P < .001). The area under the receiver-operator curve for PE
      IUGR and PE-AGAf were 0.94 (95% confidence interval [CI]: 0.88-1.00, P < .001)
      and 0.81 (95%CI: 0.70-0.91, P < .001), respectively. In conclusion, MtDNAcn in
      peripheral blood resulted significantly lower both in patients affected by PE
      IUGR and in those affected by PE-AGAf when compared to controls. The accuracy of
      this biomarker resulted particularly good in predicting PE-IUGR.

PMID- 30296911
TI  - Contemporary Insights from Biblical Combat Veterans through the Lenses of Moral
      Injury and Post-Traumatic Stress Disorder.
AB  - This psychological exegesis reconsiders biblical characters through recent
      theories on moral injury and post-traumatic stress disorder (PTSD). The purposes
      of this article are to shed new light on these characters and to engage in
      conversations of what the findings may mean for pastoral care and their
      connections to theology. The findings include the proposal of four categorical
      types of combat veterans that illustrate the development of PTSD, resilience,
      moral injury, and unfaltering abidance to the warrior ethics.

PMID- 30296912
TI  - The Effect of Sphenopalatine Block on the Postoperative Pain of Endoscopic Sinus
      Surgery: A Meta-analysis.
AB  - Objectives The use of sphenopalatine ganglion block (SPGB) with a local
      anesthetic to decrease postoperative pain after endoscopic sinus surgery (ESS) is
      controversial. We investigated the role of a perioperative SPB to minimize
      postoperative pain related to ESS in patients with chronic sinusitis through a
      systematic review of the relevant literature. Data Sources PubMed, SCOPUS, Google
      Scholar, Embase, and the Cochrane Register of Controlled Trials. Review Methods
      We screened the relevant literature published before June 2018. Eight articles
      that compared perioperative SPGB (treatment group) with a placebo or no treatment
      (control group) were included for this analysis of the outcomes, which included
      perioperative morbidities in ESS. For quantitative variables, the standardized
      mean difference was applied to standardize and summate the results of the
      studies, and the odds ratio was used in outcome of incidence analysis. Results
      Intraoperative bleeding ( P < .0001), postoperative pain ( P = .0001), nausea and
      vomiting ( P = .0117), and recovery from sedation ( P < .0001) in the treatment
      group were significantly reduced compared with the control group. No significant
      adverse effects were reported in the enrolled studies. In subgroup analyses
      according to the SPGB approach (transoral or transnasal), the transnasal approach
      showed higher positive effects on intraoperative bleeding and postoperative pain
      compared to the transoral approach. Conclusion In our study, SPGB combined with a
      local anesthetic for ESS effectively reduced intra-and postoperative morbidities.
      This procedure showed no significant adverse effects. Given the ease and
      effectiveness of this procedure, the transnasal approach should be highly
      recommended as a routine procedure compared to the transoral approach.

PMID- 30296913
TI  - How visual memory changes with intervening recall.
AB  - Being asked to recount a visual memory is common in educational settings, spatial
      navigation, and crime investigation. Previous studies show that recounting one's
      memory can benefit subsequent memory, but most of this work either used verbal
      materials or conflated category memory with memory for visual details. To test
      whether recounting may introduce visually-specific interference effects, we
      tested people's memory for photographs of objects, but introduced an intervening
      phase in which people described their memory. We separated memory for the
      specific exemplar from memory for the basic-level category. Contrary to recent
      findings on maps and colours, the intervening retrieval practice did not
      consistently strengthen exemplar memory of objects. Instead, recounting one's
      visual memory appeared to introduce interference that sometimes cancelled the
      benefit of increased retrieval effort. Delaying the final memory test by 24 hr
      increased the benefit of retrieval practice. These findings suggest that
      intervening retrieval has multiple effects on visual memory. Instead of being a
      snapshot, this memory constantly changes with retrieval practice and with time.

PMID- 30296914
TI  - Mutated Thyroid Hormone Transporter OATP1C1 Associates with Severe Brain
      Hypometabolism and Juvenile Neurodegeneration.
AB  - BACKGROUND: Thyroid hormones (TH) are essential for brain development and
      function. The TH transporters monocarboxylate transporter 8 (MCT8) and organic
      anion transporter1 C1 (OATP1C1) facilitate the transport of TH across the blood
      brain barrier and into glia and neuronal cells in the brain. Loss of MCT8
      function causes Allan-Herndon-Dudley syndrome (AHDS, OMIM 300523) characterized
      by severe intellectual and motor disability due to cerebral hypothyroidism. Here,
      the first patient with loss of OATP1C1 function is described. The patient is a
      15.5-year-old girl with normal development in the first year of life, who
      gradually developed dementia with spasticity and intolerance to cold. Brain
      imaging demonstrated gray and white matter degeneration and severe glucose
      hypometabolism. METHODS: Exome sequencing of the patient and parents was
      performed to identify the disease-causing mutation, and the effect of the
      mutation was studied through a panel of in vitro experiments, including thyroxine
      uptake studies, immunoblotting, and immunocytochemistry. Furthermore, the
      clinical effects of treatment with the triiodothyronine analogue
      triiodothyroacetic acid (Triac) are described. RESULTS: Exome sequencing
      identified a homozygous missense mutation in OATP1C1, changing the highly
      conserved aspartic acid 252 to asparagine (D252N). In vitro, the mutated OATP1C1
      displays impaired plasma membrane localization and decreased cellular thyroxine
      uptake. After treatment with Triac, the clinical condition improved in several
      domains. CONCLUSIONS: This is the first report of human OATP1C1 deficiency
      compatible with brain-specific hypothyroidism and neurodegeneration.

PMID- 30296915
TI  - Contradiction processing in schizophrenia.
AB  - INTRODUCTION: Patients with schizophrenia present clinically with difficulties in
      manipulating contradictory information in the form of loose associations, surface
      contradictions and delusional beliefs. It is to date unclear whether patients can
      detect and process information that contradicts their beliefs and prior knowledge
      and whether this capacity is related to their symptoms and the nature of
      contradictory stimuli (e.g., personally significant information, emotional
      information). METHODS: We probed contradiction processing in patients with
      schizophrenia and healthy controls using sentence verification tasks that involve
      self-referential judgements (Experiment 1) and general knowledge (Experiment 2),
      while manipulating the emotional content of the stimuli. RESULTS: We found no
      differences between patients and controls either on reaction time (Experiment 1 &
      2) or accuracy measures (Experiment 1). CONCLUSIONS: Our results show no general
      impairment in contradiction processing in schizophrenia. Rather, failures to
      detect and correct contradictions in symptoms such as formal though disorder or
      delusions could arise through a complex interplay between executive dysfunctions,
      stress and the emotional content of the information.

PMID- 30296916
TI  - High subsequent and recurrent sexually transmitted infection prevalence among
      newly diagnosed HIV-positive Thai men who have sex with men and transgender women
      in the Test and Treat cohort.
AB  - We determined subsequent and recurrent sexually transmitted infections (STIs)
      among men who have sex with men (MSM) and transgender women (TGW) in the Test and
      Treat cohort. Thai MSM and TGW adults with previously unknown HIV status were
      enrolled and tested for HIV. Chlamydia trachomatis (CT), Neisseria gonorrhoeae
      (NG), and syphilis were tested at baseline, month 12, and month 24 to identify
      subsequent STIs (any STIs diagnosed after baseline) and recurrent STIs (any
      subsequent STIs diagnosed among those with positive baseline STIs). Among 448
      participants, 17.8% were HIV-positive, the prevalence of subsequent STIs and
      recurrent STIs was 42% (HIV-positive versus HIV-negative: 66.3% versus 36.7%, p <
      0.001) and 62.3% (81% versus 52.5%, p < 0.001), respectively. Common subsequent
      STIs by anatomical site were rectal CT infection (21.7%), rectal NG infection
      (13.8%), pharyngeal NG infection (13.1%), and syphilis (11.9%). HIV-positive
      status was associated with both subsequent STIs (adjusted hazard ratio [aHR]
      2.38; 95%CI 1.64-3.45, p < 0.001) and recurrent STIs (aHR 1.83; 95%CI 1.16-2.87,
      p = 0.01). The results show that newly diagnosed HIV-positive MSM and TGW were at
      increased risk of STIs despite being in the healthcare system. STI educational
      counseling is necessary to improve STI outcomes among MSM and TGW in both HIV
      prevention and treatment programs.

PMID- 30296917
TI  - Understanding the Role of Telomere Dynamics in Normal and Dysfunctional Human
      Reproduction.
AB  - In modern society, fertility problems and demand of treatment seem to be on the
      rise, which led to an increased interest in research regarding human
      reproduction. Among these efforts, the study of the molecular senescence process
      has gain notorious popularity as aging is one of the most important variables
      involved in reproductive capacity and since the comprehension of telomere
      dynamics has become an important and influential theme. This new knowledge
      regarding the reproductive aging process is expected to offer new tools to
      understand the acquisition, maintenance, and loss of fertility potential.
      Therefore, this review seeks to clarify the relevance of molecular aging
      (evaluated by telomere shortening) in human reproduction, showing that it is a
      dynamic and variable process modulated according to the specific tissue and stage
      of development. As well, it is discussed how telomere status influence the
      development and progression of some fertility pathologies, the outcome of
      assisted reproductive treatments, and programming of aging in the offspring.

PMID- 30296918
TI  - Attachment to God and Death Anxiety in Later Life: Does Race Matter?
AB  - Research suggests that religion plays a critical role in individuals' attitudes
      toward death in later life. The purpose of this study is to investigate whether a
      previously unexamined aspect of religion-secure attachment to God-is associated
      with death anxiety among U.S. older adults and whether this association varies
      across race. Using longitudinal data from a representative sample of adults aged
      65 and older ( N = 936), the analyses reveal that secure attachment to God is
      associated with a decrease in death anxiety over time. Furthermore, the negative
      association between secure attachment to God and change in death anxiety is
      greater for older Blacks than their White counterparts. These results indicate
      that religion serves a protective function against death anxiety in later life.
      Moreover, religion provides greater psychological benefits for older Blacks than
      older Whites, reinforcing a long-standing claim that religion is particularly
      valuable for individuals from marginalized backgrounds.

PMID- 30296919
TI  - Medication-related osteonecrosis of the jaw: An institution's experience.
AB  - OBJECTIVES: This study aimed to evaluate and report the outcomes associated with
      the management of patients who were treated surgically for medication-related
      osteonecrosis of the jaw (MRONJ). METHODS: Demographic and medical profiles of
      patients with a diagnosis of MRONJ were created. The type of surgical treatment,
      complications, and treatment outcomes were identified. RESULTS: Twenty-one
      patients with an average age of 68.42 years (range 40-90 years) were included.
      Nineteen patients had only mandible involvement, one patient had only maxilla
      involvement, and one patient had both mandible and maxilla involvement. Thirteen
      patients underwent marginal resections. Eight patients underwent segmental
      resection of the mandible with immediate reconstruction. Nineteen patients healed
      without any complications. Two patients who had undergone segmental resection of
      the mandible experienced postoperative complications and needed a second surgery
      to achieve primary closure. DISCUSSION: Advanced MRONJ can effectively be treated
      with resective surgery in combination with medical treatment.

PMID- 30296920
TI  - Efficacy of dry needling in patients with myofascial temporomandibular disorders
      related to the masseter muscle.
AB  - OBJECTIVE: This randomized, single-center clinical trial aimed to compare the
      efficacy of superficial dry needling (SDN) and deep dry needling (DDN) in
      patients with myofascial temporomandibular disorder (MTMD) related to the
      masseter muscle. METHODS: Forty patients showing MTMD with trigger points in the
      masseter muscle were randomly assigned to groups. Dry needling of the masseter
      muscle was performed once per week for three weeks. Pressure pain threshold (PPT)
      measurements, visual analog scale scores, and maximal jaw opening were assessed.
      RESULTS: Both patient groups showed significant pain reduction, but the SDN group
      showed significantly better pain reduction. The PPT measurements obtained in the
      follow-up examinations at three and six weeks were significantly better than the
      values in SDN and DDN groups. DISCUSSION: SDN showed better pain-reduction
      efficacy in patients with MTMD. Further research with a larger size sample and a
      longer follow-up period will help elucidate the benefits of SDN.

PMID- 30296921
TI  - "It's Hard Work": A Feminist Political Economy Approach to Reconceptualizing
      "Work" in the Cancer Context.
AB  - Within mainstream cancer literature, policy documents, and clinical practice,
      "work" is typically characterized as being synonymous with paid employment, and
      the problem of work is situated within the "return to work" discourse. The work
      that patients perform in managing their health, care, and everyday life at times
      of illness, however, is largely overlooked and unsupported. Drawing on feminist
      political economy theory, we report on a qualitative study of 12 women living
      with cancer. Major findings show that the work of patienthood cut across multiple
      fields of practice and included both paid and unpaid labor. The most prevalent
      types of work included illness work, body work, identity work, everyday work,
      paid employment and/or the work of maintaining income, and coordination work. The
      findings of this study disrupt popular conceptualizations of work and illuminate
      the nuanced and often invisible work that cancer patients may encounter, and the
      health consequences and inequities therein.

PMID- 30296922
TI  - Novel insights into the dynamics behavior of glucagon-like peptide-1 receptor
      with its small molecule agonists.
AB  - The glucagon-like peptide-1 receptor (GLP-1R) is a well-known target of
      therapeutics industries for the treatment of various metabolic diseases like type
      2 diabetes and obesity. The structural-functional relationships of small molecule
      agonists and GLP-1R are yet to be understood. Therefore, an attempt was made on
      structurally known GLP-1R agonists (Compound 1, Compound 2, Compound A, Compound
      B, and (S)-8) to study their interaction with the extracellular domain of GLP-1R.
      In this study, we explored the dynamics, intrinsic stability, and binding
      mechanisms of these molecules through computational modeling, docking, molecular
      dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area
      (MM/PBSA) binding free energy estimation. Molecular docking study depicted that
      hydrophobic interaction (pi-pi stacking) plays a crucial role in maintaining the
      stability of the complex, which was also supported by intermolecular analysis
      from MD simulation study. Principal component analysis suggested that the
      terminal ends along with the turns/loops connecting adjacent helix and strands
      exhibit a comparatively higher movement of main chain atoms in most of the
      complexes. MM/PBSA binding free energy study revealed that non-polar solvation
      (van der Waals and electrostatic) energy subsidizes significantly to the total
      binding energy, and the polar solvation energy opposes the binding agonists to
      GLP-1R. Overall, we provide structural features information about GLP-1R
      complexes that would be conducive for the discovery of new GLP-1R agonists in the
      future for the treatment of various metabolic diseases. Communicated by Ramaswamy
      H. Sarma.

PMID- 30296923
TI  - Individuals With the Rare Disease Pemphigus: A Quest for Diagnostic.
AB  - This qualitative study conducted in France of "individuals living with a
      pemphigus" (ILPs; N = 54) highlights the taxing diagnostic trajectory of those
      suffering from these rare autoimmune diseases. Beyond enduring a diagnostic
      period that may prove long, during their numerous medical appointments, these
      individuals internalize the expectations of the medical professionals who are
      treating them. In some cases, numerous inconclusive medical tests and, at times,
      a doctor's condescension may push the patient toward a process of renunciation.
      This article relates the ILPs' critiques of the medical work conducted during the
      trying diagnostic period.

PMID- 30296924
TI  - Nothing and Everything: Fibromyalgia as a Diagnosis of Exclusion and Inclusion.
AB  - The diagnostic process promises a label that validates patients' embodied
      experiences and a road map for living with and treating illness. Drawing on 31
      qualitative interviews with women and men in Canada and the United Kingdom who
      have been diagnosed with fibromyalgia (FM), in this article, I examine the
      participants' experiences of the diagnostic process and how they feel about
      receiving this label. The interviews reflect that the FM label is plagued by
      uncertainty because the diagnosis is based on the absence of verifiable
      pathology. The respondents' narratives also reveal that FM is a vague diagnosis
      that includes a multitude of symptoms, overlaps with several other diagnoses, and
      results in feelings of doubt regarding whether it is the correct label. Thus, the
      participants' narratives reflect that the FM diagnosis is largely an empty
      promise because it fails to provide definitive answers or confer meaning and
      legitimacy to their illness experiences.

PMID- 30296925
TI  - Block of Granulocyte-Macrophage Colony-Stimulating Factor Prevents Inflammation
      Induced Preterm Birth in a Mouse Model for Parturition.
AB  - OBJECTIVE: A multitude of factors promotes inflammation in the reproductive tract
      leading to preterm birth. Macrophages peak in the cervix prior to birth and their
      numbers are increased by the cytokine granulocyte-macrophage colony-stimulating
      factor (GM-CSF). We hypothesize GM-CSF is produced from multiple sites in the
      genital tract and is a key mediator in preterm birth. STUDY DESIGN: Ectocervical,
      endocervical, and amniotic fluid mesenchymal stem cells were treated with
      lipopolysaccharide (LPS), and the concentration and expression of GM-CSF was
      measured. Pregnant CD-1 mice on gestational day 17 received LPS and an
      intravenous injection of either anti-mouse GM-CSF or control antibody. After 6
      hours, the preterm birth rate was recorded. RESULTS: Treatment with LPS increased
      the GM-CSF concentration and messenger RNA expression after 24 hours in all 3
      cell lines ( P < .01). Mice treated with LPS and the GM-CSF antibody had a
      preterm birth rate of 25%, compared to a 66.7% preterm birth rate in controls,
      within 6 hours ( P < .05, chi2). Treatment with the anti-mouse GM-CSF antibody
      decreased the concentration of GM-CSF in the mouse serum ( P < .01) but did not
      alter the number of macrophages or collagen content in the cervix. CONCLUSION:
      These studies demonstrate that GM-CSF is produced from multiple sites in the
      genital tract and that treatment with an antibody to GM-CSF prevents preterm
      birth. Curiously, the anti-mouse GM-CSF antibody did not decrease the number of
      macrophages in the cervix. Further research is needed to determine whether
      antibodies to GM-CSF can be utilized as a therapeutic agent to prevent preterm
      birth.

PMID- 30296926
TI  - Exploratory Research Focusing on Oral Cancer Prevention: Challenges of Dealing
      With Informational and Cognitive Barriers.
AB  - Oral cancer is a considerable public health problem, and a low level of awareness
      and knowledge about this tumor and its risk factors is prevalent. To gain a
      profound understanding of risks groups and to identify suitable communication
      strategies for a prevention campaign in Northern Germany, an exploratory research
      was realized. In semistructured face-to-face interviews, the participants of the
      study ( n = 28) described their individual oral cancer-related perceptions and
      information-seeking behaviors. A computer-assisted qualitative data analysis
      showed a vague but also deterring picture of cancer combined with restricted
      attitudes toward the topic and an inactive or even avoiding information behavior.
      Four underlying cognitive patterns of self-distancing were identified: (a)
      optimistic bias, (b) fatalism, (c) hedonism, and (d) pragmatism. The main
      challenge of oral cancer prevention is to deal with the target groups'
      informational and cognitive barriers.

PMID- 30296927
TI  - Survival following rectal cancer surgery: does the age matter?
AB  - INTRODUCTION: Information regarding rectal cancer surgery outcomes and survival
      benefits in the elderly is sparse. Radical rectal surgery can be associated with
      substantial morbidity and mortality. We investigated age-specific survival for
      patients undergoing radical rectal surgery to determine outcomes in elderly
      patients Methods: Over a 10-year period data on all patients who underwent rectal
      cancer surgery was performed. Patients were grouped according to age and eight
      other variables including cancer stage (Duke's/TNM). Data analysed using computer
      program R. Kaplan-Meier survival curves estimated for age groups and compared
      using a modified log-rank permutation test. Survival curves fitted using Cox
      proportional hazard models and hazard ratios obtained Results: About 374 patients
      underwent surgery. Survival percentages at 1 year by age group are 91.3% for age
      <50, and 75.5% for age >80. At 5 years these are 87.0% for age <50 and 57.1% for
      >80. Overall the variation among the survival curves for the age groups is
      significant (p < .001). The hazard ratio for over the 80+ with the age group <50
      as the reference is 4.79 (95% CI: 1.44-15.92) and is significant (p = .011)
      Conclusion: Overall survival is significantly less in the elderly. There is a
      striking reduction in survival in >80 year olds in the first post-operative year.
      This study highlights that care must be taken in deciding whether radical surgery
      should be offered to those patients and careful consideration is given to allow
      the best overall survival and quality of life.

PMID- 30296928
TI  - Student nurses' perceptions of FacebookTM as an interactive learning platform in
      nursing education.
AB  - BACKGROUND: The use of FacebookTM in nursing education is under-researched.
      OBJECTIVE: To assess students' perceptions of using FacebookTM as an educational
      mean to support their study. METHODS: One group pretest-posttest study was
      conducted in one nursing school in Jordan. FacebookTM pages were created for two
      nursing courses. Students completed a questionnaire about students' perception of
      using FacebookTM as educational platform in the first lecture of the semester as
      a pre-test, and then at the end of the semester as a post-test; after interacting
      with the created FacebookTM page. RESULTS: Students perceived that FacebookTM is
      an effective tool for nursing education (n = 119, 78.8%). It can facilitate the
      communication, ease access to course materials, and provide support for students.
      However, a few students believed that FacebookTM is a distraction from study,
      requires users to have special skills, and does not protect privacy. CONCLUSION:
      This preliminary evaluation revealed that FacebookTM can be used as an
      instructional tool to support nursing education.

PMID- 30296929
TI  - Successful Percutaneous Recanalization of a Chronically Occluded Inferior Vena
      Cava in a Young Child.
AB  - Young children with congenital heart disease are undergoing an increasing number
      of catheter-based interventions. These procedures can lead to obstruction of
      large central veins, making future interventions more challenging or even
      impossible. We present a young child with a chronically occluded inferior vena
      cava (IVC) secondary to prior catheterization-based interventions for congenital
      heart disease. The IVC was recanalized with serial angioplasty and stent
      placement with continued patency for over two years. Despite the long duration of
      obstruction, the IVC was successfully recanalized, eliminating the potential
      consequences of long-term IVC obstruction and making it easier for future
      catheter-based interventions, if needed.

PMID- 30296930
TI  - Stigma and the in(visible) perspectives and expectations of home oxygen therapy
      among people with chronic breathlessness syndrome: A qualitative study.
AB  - BACKGROUND: Chronic breathlessness syndrome in the context of advancing disease
      is distressing for all concerned. Oxygen is commonly prescribed in this setting;
      however, little is known about the perspectives of breathless people who either
      are on oxygen or are yet to have it prescribed. AIM: To understand and describe
      the perspectives and experiences of breathless people towards oxygen use at home.
      DESIGN: This qualitative study utilised an interpretive description approach
      using semi-structured interviews and thematic analysis. SETTING/PARTICIPANTS: A
      total of 19 people with chronic breathlessness syndrome living in South Australia
      participated in semi-structured interviews. Participants were divided into sub
      groups according to whether they were chronically breathless and (1) not using
      home oxygen ( n = 6), (2) using funded home oxygen for severe hypoxaemia ( n = 7)
      and (3) using home oxygen for palliation outside of funding guidelines ( n = 6).
      RESULTS: Three main themes were identified: (1) managing distress and living with
      chronic breathlessness syndrome, with or without oxygen, requires a range of self
      management strategies; (2) expectations of oxygen use: 'Not as good as I thought
      it would be'; and (3) the stigma of using oxygen: the visible and invisible.
      CONCLUSION: People living with chronic breathlessness struggle daily with both
      the progression of the underlying disease and the distressing nature of the
      syndrome. While oxygen does provide benefit for some people, its use and the
      perceptions of its use are often associated with both the visible and invisible
      manifestations of stigma. Clinicians need to promote self-management strategies
      and give careful thought to the prescribing of home oxygen, especially outside
      the current funding guidelines.

PMID- 30296931
TI  - Impact of dapagliflozin on left ventricular diastolic function of patients with
      type 2 diabetic mellitus with chronic heart failure.
AB  - BACKGROUND: The objective of this study was to investigate the impact of sodium
      glucose cotransporter type 2 (SGLT2) inhibitors on left ventricular (LV)
      diastolic function of type 2 diabetes mellitus (T2DM) patients with heart failure
      (HF). METHODS: This trial was a prospective multicenter study of 58 T2DM patients
      with stable HF at five institutions in Japan. Patients who had been taking at
      least one antidiabetic drugs other than SGLT2 inhibitors started the
      administration of 5 mg/day of dapagliflozin. The physical examinations, blood
      tests, and echocardiography were performed at baseline and 6 months after
      administration of dapagliflozin. The primary endpoint was defined as a change in
      mitral inflow E and mitral e' annular velocities (E/e') between baseline and 6
      months after the administration of dapagliflozin. The secondary end points
      consisted of a change in brain natriuretic peptide (BNP), LV mass index (LVMI)
      and left atrial volume index (LAVI). RESULTS: E/e' significantly decreased from
      9.3 to 8.5 cm/s (p = 0.020) 6 months after administration of dapagliflozin. LAVI
      and LVMI significantly decreased from 31 to 26 mL/m2 (p = 0.001), and from 75.0
      to 67.0 g/m2 (p < 0.001), respectively, 6 months after administration of
      dapagliflozin. No significant change was observed in BNP (from 27.9 to 28.9
      pg/mL; p = 0.132) 6 months after administration of dapagliflozin, except for a
      significant decrease from 168.8 to 114.3 pg/mL (p = 0.012) in patients with BNP
      >= 100 pg/mL. CONCLUSION: This prospective multicenter trial showed the
      beneficial effect of SGLT2 inhibitors on LV diastolic functional parameters for
      T2DM patients with HF. Our findings may thus offer a new insight into the
      management of T2DM patients. Trial registration UMIN000019789, Registered 28
      September 2014, Date of registration: 11/14/2015, Date of enrolment of the first
      participant to the trial: 6/15/2016, Date of enrolment of the last participant to
      the trial: 12/9/2017.

PMID- 30296932
TI  - First year experiences with a palliative out-patients structure for patients with
      COPD: a qualitative study of health professionals' expectations and experiences.
AB  - BACKGROUND: To improve the care of patients with advanced COPD and be able to
      address their palliative needs a new outpatient organization (CAPTAIN) was
      developed and implemented. CAPTAIN was inspired by best practice and existing
      guidelines and changed the traditional organization of an outpatient structure
      including the roles of nurses and doctors. Only sparse knowledge exists of the
      health professionals' expectations and experiences to organizational changes in
      an outpatient setting. This insight is necessary as health professionals are key
      stakeholders in implementing new structures and successfully transforming
      knowledge into practice. The aim of this study was to explore the health
      professionals' expectations and experiences of a new palliative out-patients
      structure for patients with advanced COPD. METHODS: The design was interpretive
      description as described by Thorne. Focus groups and individual interviews were
      conducted with pulmonary nurses, pulmonary doctors and municipality nurses from
      2014 to 2016. RESULTS: The overall theme was dualism. Both nurses and doctors
      were pending between aspiration and concern in their expectations to the new
      structure, meanwhile their actual experiences were pending between perceived gain
      and improvements versus consequences with the new structure. Nurses' and doctors'
      existing practice was altered and the new structure required new ways for them to
      cooperate and ways in which skills from each profession were most efficiently
      utilized. CONCLUSION: Nurses and doctors considered the new structure as a
      quality boost and it fulfilled their hope of improving the quality of care
      offered to patients with advanced COPD, however with increased work-related
      stress as a derived consequence.

PMID- 30296933
TI  - A mixed-method evaluation of the views of medical teachers on the applicability
      of the 'infant and young child feeding chapter' in Saudi medical colleges.
AB  - BACKGROUND: Lack of sufficient preparation of physicians for the provision of
      breastfeeding support and counselling has been well-documented. The development
      of training in breastfeeding medicine for medical students is currently ongoing
      worldwide. This study was conducted to gain insights into a potential framework
      for a breastfeeding education curriculum. METHODS: A mixed-method design was used
      to evaluate the opinions of medical teachers regarding current lactation
      education and the applicability of the World Health Organization 'Infant and
      young child feeding: model chapter for textbooks for medical students and allied
      health professionals' in medical colleges in Riyadh, Saudi Arabia. Twelve
      teachers from three medical schools were invited to participate in three rounds
      of research. The first round was carried out through an interview using open
      ended questions under three headings: 1) The general opinion on breastfeeding
      medicine education in medical colleges; 2) The opinion on the contents of the
      chapter under investigation; and 3) The opinion on cultural points regarding
      Saudi Arabia and breastfeeding education in medical colleges. This was followed
      by a thematic analysis. Self-administered, closed-ended questionnaires were
      created for the second round based the results of the first round. The third
      round addressed areas of disagreement in opinions. To assess the degree of
      agreement objectively, rounds 2 and 3 were analyzed according to the 5-point
      Likert scale, with responses merged to a 3-point Likert scale where appropriate.
      A consensus was reached when greater than 70% agreement achieved. RESULTS: All
      participants agreed that breastfeeding education is suboptimal. Although they
      considered the world health organization resource on infant and young child
      chapter a suitable reference for the curriculum, they agreed that modifications
      to suit the Saudi Arabian context are necessary. The medical teachers suggested a
      unique curriculum for medical students, which is similar for both genders.
      However, disagreement existed regarding the provision of extra clinical training
      to female students. CONCLUSIONS: Breastfeeding medicine education in medical
      colleges should be developed using resources that are rich in content, are
      physician-specific and take into consideration the culture.

PMID- 30296934
TI  - Neurodevelopmental and emotional-behavioral outcomes in late-preterm infants: an
      observational descriptive case study.
AB  - BACKGROUND: Over the last decade, several studies investigated the outcomes in
      children born very preterm. Only recently there has been an increasing interest
      in the late preterm infants (born between 34 + 0 and 36 + 6 weeks). This
      population is at high risk of morbidity and mortality in the first years of life.
      Other studies reported that they are also at risk of long-term developmental
      problem. Therefore, the aim of this study is to describe the neurodevelopmental
      and emotional-behavioral outcome in a sample of late preterm patients. METHODS:
      The study included late preterm children and adolescents who had neuropsychiatric
      and/or neurological symptoms. They underwent a general, neurocognitive and an
      emotional-behavioral assessment. Exclusion criteria included: patients affected
      by Central Nervous System congenital abnormalities, neurodegenerative diseases,
      genetic disorders, epilepsy, or in pharmacological treatment, or adopted
      children. A descriptive statistics analysis was performed to describe the
      sociodemographic and clinical characteristics of patients. Risk factors related
      to late preterm birth, prevalence of neurodevelopmental disorders, and cognitive
      functioning were recorded and analyzed. RESULTS: The sample included 68 LPI (45
      males and 23 females) aged from 2 to 16.3 years (mean age 7,5 years), who were
      affected by one or more neurodevelopmental disorder, including Language Disorder,
      Attention Deficit Hyperactivity Disorder, Specific Learning Disorder,
      Developmental Coordination Disorder, Intellectual Disability and Autism Spectrum
      Disorder. Moreover, in 30.8% of patients, internalizing problems (affective and
      social skills problem) were detected. CONCLUSIONS: Our results support the
      importance of a long-term surveillance of late preterm and the great need for
      more longitudinal large population studies in order to collect data on the
      neurodevelopmental outcomes of this population.

PMID- 30296935
TI  - Pathways to ensure universal and affordable access to hepatitis C treatment.
AB  - Direct-acting antivirals (DAAs) have dramatically changed the landscape of
      hepatitis C treatment and prevention. The World Health Organization has called
      for the elimination of hepatitis C as a public health threat by 2030. However,
      the discrepancy in DAA prices across low-, middle- and high-income countries is
      considerable, ranging from less than US$ 100 to approximately US$ 40,000 per
      course, thus representing a major barrier for the scale-up of treatment and
      elimination. This article describes DAA pricing and pathways to accessing
      affordable treatment, providing case studies from Australia, Egypt and Portugal.
      Pathways to accessing DAAs include developing comprehensive viral hepatitis plans
      to facilitate price negotiations, voluntary and compulsory licenses, patent
      opposition, joint procurement, and personal importation schemes. While multiple
      factors influence the price of DAAs, a key driver is a country's capacity and
      willingness to negotiate with pharmaceutical companies. If negotiations do not
      lead to a reasonable price, governments have the option to utilise flexibilities
      outlined in the Agreement on Trade-Related Aspects of Intellectual Property
      Rights. Affordable access to DAAs is underpinned by collaboration between
      government, civil society, global organisations and pharmaceutical companies to
      ensure that all patients can access treatment. Promoting these pathways is
      critical for influencing policy, improving access to affordable DAAs and
      achieving hepatitis C elimination.

PMID- 30296936
TI  - The effects of coenzyme Q10 supplementation on lipid profiles among patients with
      coronary artery disease: a systematic review and meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Chronic inflammation and increased oxidative stress significantly
      contribute in developing coronary artery disease (CAD). Hence, antioxidant
      supplementation might be an appropriate approach to decrease the incidence of
      CAD. This systematic review and meta-analysis was aimed to determine the effects
      of coenzyme Q10 (CoQ10) supplementation on lipid profile, as one of the major
      triggers for CAD, among patients diagnosed with coronary artery disease. METHODS:
      EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science were searched for
      studies prior to May 20th, 2018. Cochrane Collaboration risk of bias tool was
      applied to assess the methodological quality of included trials. I-square and Q
      tests were used to measure the existing heterogeneity across included studies.
      Considering heterogeneity among studies, fixed- or random-effect models were
      applied to pool standardized mean differences (SMD) as overall effect size.
      RESULTS: A total of eight trials (267 participants in the intervention group and
      259 in placebo group) were included in the current meta-analysis. The findings
      showed that taking CoQ10 by patients with CAD significantly decreased total
      cholesterol (SMD -1.07; 95% CI, - 1.94, - 0.21, P = 0.01) and increased HDL
      cholesterol levels (SMD 1.30; 95% CI, 0.20, 2.41, P = 0.02). We found no
      significant effects of CoQ10 supplementation on LDL-cholesterol (SMD -0.37; 95%
      CI, - 0.87, 0.13, P = 0.14), lipoprotein (a) [Lp(a)] levels (SMD -1.12; 95% CI, -
      2.84, 0.61, P = 0.20) and triglycerides levels (SMD 0.01; 95% CI, - 0.22, 0.24, P
      = 0.94). CONCLUSIONS: This meta-analysis demonstrated the promising effects of
      CoQ10 supplementation on lowering lipid levels among patients with CAD, though it
      did not affect triglycerides, LDL-cholesterol and Lp(a) levels.

PMID- 30296937
TI  - Restoration of biofuel production levels and increased tolerance under ionic
      liquid stress is enabled by a mutation in the essential Escherichia coli gene
      cydC.
AB  - BACKGROUND: Microbial production of chemicals from renewable carbon sources
      enables a sustainable route to many bioproducts. Sugar streams, such as those
      derived from biomass pretreated with ionic liquids (IL), provide efficiently
      derived and cost-competitive starting materials. A limitation to this approach is
      that residual ILs in the pretreated sugar source can be inhibitory to microbial
      growth and impair expression of the desired biosynthetic pathway. RESULTS: We
      utilized laboratory evolution to select Escherichia coli strains capable of
      robust growth in the presence of the IL, 1-ethyl-3-methyl-imidizolium acetate
      ([EMIM]OAc). Whole genome sequencing of the evolved strain identified a point
      mutation in an essential gene, cydC, which confers tolerance to two different
      classes of ILs at concentrations that are otherwise growth inhibitory. This
      mutation, cydC-D86G, fully restores the specific production of the bio-jet fuel
      candidate D-limonene, as well as the biogasoline and platform chemical
      isopentenol, in growth medium containing ILs. Similar amino acids at this
      position in cydC, such as cydC-D86V, also confer tolerance to [EMIM]OAc. We show
      that this [EMIM]OAc tolerance phenotype of cydC-D86G strains is independent of
      its wild-type function in activating the cytochrome bd-I respiratory complex.
      Using shotgun proteomics, we characterized the underlying differential cellular
      responses altered in this mutant. While wild-type E. coli cannot produce
      detectable amounts of either product in the presence of ILs at levels expected to
      be residual in sugars from pretreated biomass, the engineered cydC-D86G strains
      produce over 200 mg/L D-limonene and 350 mg/L isopentenol, which are among the
      highest reported titers in the presence of [EMIM]OAc. CONCLUSIONS: The optimized
      strains in this study produce high titers of two candidate biofuels and
      bioproducts under IL stress. Both sets of production strains surpass production
      titers from other IL tolerant mutants in the literature. Our application of
      laboratory evolution identified a gain of function mutation in an essential gene,
      which is unusual in comparison to other published IL tolerant mutants.

PMID- 30296939
TI  - Correction to: Photography-based method for assessing fluorescein clearance test
      in dogs.
AB  - The original article [1] contained an error whereby the respective legends of
      Figs. 2 and 3 were mistakenly interchanged. This error has now been amended.

PMID- 30296938
TI  - PHLI-seq: constructing and visualizing cancer genomic maps in 3D by phenotype
      based high-throughput laser-aided isolation and sequencing.
AB  - Spatial mapping of genomic data to tissue context in a high-throughput and high
      resolution manner has been challenging due to technical limitations. Here, we
      describe PHLI-seq, a novel approach that enables high-throughput isolation and
      genome-wide sequence analysis of single cells or small numbers of cells to
      construct genomic maps within cancer tissue in relation to the images or
      phenotypes of the cells. By applying PHLI-seq, we reveal the heterogeneity of
      breast cancer tissues at a high resolution and map the genomic landscape of the
      cells to their corresponding spatial locations and phenotypes in the 3D tumor
      mass.

PMID- 30296940
TI  - CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens.
AB  - Pooled CRISPR screens allow researchers to interrogate genetic causes of complex
      phenotypes at the genome-wide scale and promise higher specificity and
      sensitivity compared to competing technologies. Unfortunately, two problems
      exist, particularly for CRISPRi/a screens: variability in guide efficiency and
      large rare off-target effects. We present a method, CRISPhieRmix, that resolves
      these issues by using a hierarchical mixture model with a broad-tailed null
      distribution. We show that CRISPhieRmix allows for more accurate and powerful
      inferences in large-scale pooled CRISPRi/a screens. We discuss key issues in the
      analysis and design of screens, particularly the number of guides needed for
      faithful full discovery.

PMID- 30296941
TI  - Food perception without ingestion leads to metabolic changes and irreversible
      developmental arrest in C. elegans.
AB  - BACKGROUND: Developmental physiology is very sensitive to nutrient availability.
      For instance, in the nematode Caenorhabditis elegans, newly hatched L1-stage
      larvae require food to initiate postembryonic development. In addition, larvae
      arrested in the dauer diapause, a non-feeding state of developmental arrest that
      occurs during the L3 stage, initiate recovery when exposed to food. Despite the
      essential role of food in C. elegans development, the contribution of food
      perception versus ingestion on physiology has not been delineated. RESULTS: We
      used a pharmacological approach to uncouple the effects of food (bacteria)
      perception and ingestion in C. elegans. Perception was not sufficient to promote
      postembryonic development in L1-stage larvae. However, L1 larvae exposed to food
      without ingestion failed to develop upon return to normal culture conditions,
      instead displaying an irreversible arrest phenotype. Inhibition of gene
      expression during perception rescued subsequent development, demonstrating that
      the response to perception without feeding is deleterious. Perception altered DAF
      16/FOXO subcellular localization, reflecting activation of insulin/IGF signaling
      (IIS). The insulin-like peptide daf-28 was specifically required, suggesting
      perception in chemosensory neurons, where it is expressed, regulates peptide
      synthesis and possibly secretion. However, genetic manipulation of IIS did not
      modify the irreversible arrest phenotype caused by food perception, revealing
      that wild-type function of the IIS pathway is not required to produce this
      phenotype and that other pathways affected by perception of food in the absence
      of its ingestion are likely to be involved. Gene expression and Nile red staining
      showed that food perception could alter lipid metabolism and storage. We found
      that starved larvae sense environmental polypeptides, with similar molecular and
      developmental effects as perception of bacteria. Environmental polypeptides also
      promoted recovery from dauer diapause, suggesting that perception of polypeptides
      plays an important role in the life history of free-living nematodes.
      CONCLUSIONS: We conclude that actual ingestion of food is required to initiate
      postembryonic development in C. elegans. We also conclude that polypeptides are
      perceived as a food-associated cue in this and likely other animals, initiating a
      signaling and gene regulatory cascade that alters metabolism in anticipation of
      feeding and development, but that this response is detrimental if feeding does
      not occur.

PMID- 30296942
TI  - CRISPR-mediated deletion of prostate cancer risk-associated CTCF loop anchors
      identifies repressive chromatin loops.
AB  - BACKGROUND: Recent genome-wide association studies (GWAS) have identified more
      than 100 loci associated with increased risk of prostate cancer, most of which
      are in non-coding regions of the genome. Understanding the function of these non
      coding risk loci is critical to elucidate the genetic susceptibility to prostate
      cancer. RESULTS: We generate genome-wide regulatory element maps and performed
      genome-wide chromosome confirmation capture assays (in situ Hi-C) in normal and
      tumorigenic prostate cells. Using this information, we annotate the regulatory
      potential of 2,181 fine-mapped prostate cancer risk-associated SNPs and predict a
      set of target genes that are regulated by prostate cancer risk-related H3K27Ac
      mediated loops. We next identify prostate cancer risk-associated CTCF sites
      involved in long-range chromatin loops. We use CRISPR-mediated deletion to remove
      prostate cancer risk-associated CTCF anchor regions and the CTCF anchor regions
      looped to the prostate cancer risk-associated CTCF sites, and we observe up to
      100-fold increases in expression of genes within the loops when the prostate
      cancer risk-associated CTCF anchor regions are deleted. CONCLUSIONS: We identify
      GWAS risk loci involved in long-range loops that function to repress gene
      expression within chromatin loops. Our studies provide new insights into the
      genetic susceptibility to prostate cancer.

PMID- 30296943
TI  - Usefulness of carotid ultrasonography in the diagnosis of coronary artery disease
      in patients undergoing exercise echocardiography.
AB  - BACKGROUND: Relationship between carotid and coronary artery disease (CAD) in
      patients undergoing invasive and non-invasive test is unclear. The aim of the
      study is to evaluate whether carotid disease is associated with CAD in patients
      submitted to exercise echocardiography (EE) and if it improves the EE ability to
      predict CAD. METHODS: We retrospectively studied 156 subjects without previous
      vascular disease who underwent EE, carotid ultrasonography and coronary
      angiography between 2002 and 2013. Positive EE was defined as exercise induced
      wall motion abnormalities, carotid disease according to Manheim and American
      Society of Echocardiography Consensus and significant CAD as stenosis >=50%.
      RESULTS: Eighty-nine (57.1%) subjects had significant CAD. Factors associated
      with CAD in multivariate analysis were fasting plasma glucose (odds ratio [OR]
      1.02, p = 0.031), pre-test probability of CAD > 65% (OR 3.71, p < 0.001),
      positive EE (OR 10.51, p < 0.001) and carotid plaque (CP) presence (OR 2.95, p =
      0.013). There was neither statistical significant difference in area under the
      curve after addition of CP to EE results (0.77 versus 0.81, p = 0.525) nor
      sensitivity, specificity, predictive values or efficiency. CP presence
      reclassified as very high-risk according to Systematic COronary Risk Evaluation
      13 patients (34.2%) with negative EE and 22 (33.3%) without CAD. CONCLUSION: CP
      is associated with CAD in patients undergoing EE, however its addition to EE does
      not improve CAD prediction, probably due to insufficient statistical power. CP
      reclassified one third of patients to very high-risk category despite negative EE
      or CAD absence, these subjects benefit from aggressive primary prevention
      interventions.

PMID- 30296944
TI  - Description of a novel RyR2 mutation in a juvenile patient with symptomatic
      catecholaminergic polymorphic ventricular tachycardia in sleep and during
      exercise: a case report.
AB  - BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is an inherited
      disease presenting with arrhythmic events during physical exercise or emotional
      stress. If untreated, catecholaminergic polymorphic ventricular tachycardia is a
      highly lethal condition: About 80% of affected individuals experience recurrent
      syncope, and 30% experience cardiac arrest. Catecholaminergic polymorphic
      ventricular tachycardia is caused by mutations in genes encoding ryanodine
      receptor type 2 (RyR2) and cardiac calsequestrin (CASQ2). In cases of
      sympathoadrenergic activation, both mutations result in a spontaneous Ca2+
      release in cardiac cells, facilitating ventricular arrhythmias. CASE
      PRESENTATION: We present a case of a 17-year-old Caucasian boy who survived
      sudden cardiac death caused by ventricular fibrillation while performing running
      exercise in a fitness center. The diagnostic workup included blood tests,
      coronary angiography, electrophysiological testing, and cardiac magnetic
      resonance imaging, but all results were normal. Because the patient's medical
      history included recurrent syncope during physical and emotional stress, we
      strongly suspected catecholaminergic polymorphic ventricular tachycardia as the
      underlying disease. Genetic screening was performed and confirmed the diagnosis,
      revealing a new heterozygous point mutation in the gene for RyR2, c.12520T>A
      (p.F4174 l, exon 90, RyR2 gene). The patient was discharged from our hospital
      after undergoing implantation of an implantable cardioverter defibrillator for
      secondary prevention. Shortly after implantation, the implantable cardioverter
      defibrillator terminated a sustaining ventricular tachycardia episode by
      antitachycardic pacing. This episode occurred early in the morning while the
      patient was asleep. CONCLUSIONS: We present a case of catecholaminergic
      polymorphic ventricular tachycardia associated with a novel single point mutation
      in the RyR2 gene, which, to the best of our knowledge, has not been described in
      the literature so far. Our patient experienced arrhythmic events under both
      resting conditions and physical activity, an uncommon finding in patients with
      catecholaminergic polymorphic ventricular tachycardia. This novel mutation may
      cause arrhythmias independent of sympathoadrenergic stimulation, but further
      evidence is needed to prove causality.

PMID- 30296946
TI  - Correction to: A loop-mediated isothermal amplification assay for the detection
      and quantification of JC polyomavirus in cerebrospinal fluid: a diagnostic and
      clinical management tool and technique for progressive multifocal
      leukoencephalopathy.
AB  - In the original publication of article [1], '20 * 101 copies', which is in the
      sentence 'As seen in Fig. 4, the sensitivity of the specimens containing equal to
      or more than 20 * 101 copies in 2 MUL of extracted DNA (equivalent to >=3.0 * 103
      copies/mL CSF) was 100% (29/29)' changes to '2.0 * 101 copies' in results
      section. The publisher apologizes to the readers and authors for the
      inconvenience.

PMID- 30296945
TI  - Should anti-EGFR mAbs be discontinued for conversion surgery in untreated right
      sided metastatic colorectal cancer? A systematic review and meta-analysis.
AB  - BACKGROUND: Previous studies have demonstrated that left-sided tumors have better
      prognoses than right-sided tumors in RAS wild-type mCRC (metastatic colorectal
      cancer) patients, while anti-EGFR mAbs appear to have no advantage compared with
      bevacizumab for right-sided tumors in these patients. Nevertheless, it remains
      unclear whether primary tumor location affects patients' options for potentially
      curative resection. METHODS: PubMed, the Cochrane Library, Embase, ASCO, and ESMO
      conference abstracts were searched. The inclusion criteria were RCT (randomized
      controlled trials) studies that evaluated the efficacy of anti-EGFR mAbs based on
      primary tumor location. The outcomes included ORR, ETS, and DpR. ORs for ORR were
      calculated with 95% confidence intervals by Comprehensive Meta-Analysis, version
      2.0. RESULT: Nine studies including nine RCTs were analyzed. Regardless of left-
      or right-sided tumors, the ORRs for anti-EGFR mAb (left-sided: 80.2%, 95% CI, 47
      95%; I2 = 76.9%; right-sided: 46.1%, 95% CI, 39.4-53.0%; I2 = 18.9%) were both
      higher than the control arm including chemotherapy with or without bevacizumab.
      The ORs for anti-EGFR mAbs have a significant benefit compared with chemotherapy
      with or without bevacizumab in left-sided tumors (OR = 2.19, 95% CI, 1.41-3.38; P
      < 0.001). For right-sided tumors, anti-EGFR mAbs still significantly improved the
      ORR compared with chemotherapy alone (OR = 1.75, 95% CI, 1.05-2.90; P = 0.03),
      and the OR numerically favored the anti-EGFR mAbs compared with bevacizumab (OR =
      1.281, 95% CI, 0.77-2.12; P = 0.335). The data of ETS and DpR from three RCTs
      also favored the EGFR antibody irrespective of tumor location. Resection data on
      differentiating tumor locations is inconclusive. For right-sided tumors, it
      should be noted that median PFS and OS were comparable for patients who achieved
      ETS in both treatment arms. CONCLUSIONS: Anti-EGFR mAbs have advantages in the
      tumor shrinkage regardless of left- or right-sided tumors, which is important for
      conversion therapy. For right-sided tumors, anti-EGFR mAbs should remain the
      first choice for potentially curative resection in RAS wild-type mCRC patients.
      ETS may represent a subgroup of patients with right-sided tumors who might
      benefit from the anti-EGFR mAb.

PMID- 30296947
TI  - Effects of social defeat stress on dopamine D2 receptor isoforms and proteins
      involved in intracellular trafficking.
AB  - BACKGROUND: Chronic social defeat stress induces depression and anxiety-like
      behaviors in rodents and also responsible for differentiating defeated animals
      into stress susceptible and resilient groups. The present study investigated the
      effects of social defeat stress on a variety of behavioral parameters like social
      behavior, spatial learning and memory and anxiety like behaviors. Additionally,
      the levels of various dopaminergic markers, including the long and short form of
      the D2 receptor, and total and phosphorylated dopamine and cyclic adenosine 3',5'
      monophosphate regulated phosphoprotein-32, and proteins involved in intracellular
      trafficking were assessed in several key brain regions in young adult mice.
      METHODS: Mouse model of chronic social defeat was established by resident
      intruder paradigm, and to evaluate the effect of chronic social defeat, mice were
      subjected to behavioral tests like spontaneous locomotor activity, elevated plus
      maze (EPM), social interaction and Morris water maze tests. RESULTS: Mice were
      divided into susceptible and unsusceptible groups after 10 days of social defeat
      stress. The susceptible group exhibited greater decreases in time spent in the
      open and closed arms compared to the control group on the EPM. In the social
      interaction test, the susceptible group showed greater increases in submissive
      and neutral behaviors and greater decreases in social behaviors relative to
      baseline compared to the control group. Furthermore, increased expression of D2L,
      D2S, Rab4, and G protein-coupled receptor associated sorting protein-1 was
      observed in the amygdala of the susceptible group compared to the control group.
      CONCLUSION: These findings suggest that social defeat stress induce anxiety-like
      and altered social interacting behaviors, and changes in dopaminergic markers and
      intracellular trafficking-related proteins.

PMID- 30296948
TI  - A gaze-independent audiovisual brain-computer Interface for detecting awareness
      of patients with disorders of consciousness.
AB  - BACKGROUND: Currently, it is challenging to detect the awareness of patients who
      suffer disorders of consciousness (DOC). Brain-computer interfaces (BCIs), which
      do not depend on the behavioral response of patients, may serve for detecting the
      awareness in patients with DOC. However, we must develop effective BCIs for these
      patients because their ability to use BCIs does not as good as healthy users.
      METHODS: Because patients with DOC generally do not exhibit eye movements, a gaze
      independent audiovisual BCI is put forward in the study where semantically
      congruent and incongruent audiovisual number stimuli were sequentially presented
      to evoke event-related potentials (ERPs). Subjects were required to pay attention
      to congruent audiovisual stimuli (target) and ignore the incongruent audiovisual
      stimuli (non-target). The BCI system was evaluated by analyzing online and
      offline data from 10 healthy subjects followed by being applied to online
      awareness detection in 8 patients with DOC. RESULTS: According to the results on
      healthy subjects, the audiovisual BCI system outperformed the corresponding
      auditory-only and visual-only systems. Multiple ERP components, including the
      P300, N400 and late positive complex (LPC), were observed using the audiovisual
      system, strengthening different brain responses to target stimuli and non-target
      stimuli. The results revealed the abilities of three of eight patients to follow
      commands and recognize numbers. CONCLUSIONS: This gaze-independent audiovisual
      BCI system represents a useful auxiliary bedside tool to detect the awareness of
      patients with DOC.

PMID- 30296950
TI  - ETHICS IN HEALTH TECHNOLOGY ASSESSMENT: A SYSTEMATIC REVIEW.
AB  - OBJECTIVES: Integration of ethics into health technology assessment (HTA) remains
      challenging for HTA practitioners. We conducted a systematic review on social and
      methodological issues related to ethical analysis in HTA. We examined: (1)
      reasons for integrating ethics (social needs); (2) obstacles to ethical
      integration; (3) concepts and processes deployed in ethical evaluation (more
      specifically value judgments) and critical analyses of formal experimentations of
      ethical evaluation in HTA. METHODS: Search criteria included "ethic," "technology
      assessment," and "HTA". The literature search was done in Medline/Ovid, SCOPUS,
      CINAHL, PsycINFO, and the international HTA Database. Screening of citations,
      full-text screening, and data extraction were performed by two subgroups of two
      independent reviewers. Data extracted from articles were grouped into categories
      using a general inductive method. RESULTS: A list of 1,646 citations remained
      after the removal of duplicates. Of these, 132 were fully reviewed, yielding 67
      eligible articles for analysis. The social need most often reported was to inform
      policy decision making. The absence of shared standard models for ethical
      analysis was the obstacle to integration most often mentioned. Fairness and
      Equity and values embedded in Principlism were the values most often mentioned in
      relation to ethical evaluation. CONCLUSIONS: Compared with the scientific
      experimental paradigm, there are no settled proceedings for ethics in HTA nor
      consensus on the role of ethical theory and ethical expertise hindering its
      integration. Our findings enable us to hypothesize that there exists
      interdependence between the three issues studied in this work and that value
      judgments could be their linking concept.

PMID- 30296949
TI  - Engineering of glycerol utilization in Gluconobacter oxydans 621H for biocatalyst
      preparation in a low-cost way.
AB  - BACKGROUND: Whole cells of Gluconobacter oxydans are widely used in various
      biocatalytic processes. Sorbitol at high concentrations is commonly used in
      complex media to prepare biocatalysts. Exploiting an alternative process for
      preparation of biocatalysts with low cost substrates is of importance for
      industrial applications. RESULTS: G. oxydans 621H was confirmed to have the
      ability to grow in mineral salts medium with glycerol, an inevitable waste
      generated from industry of biofuels, as the sole carbon source. Based on the
      glycerol utilization mechanism elucidated in this study, the major polyol
      dehydrogenase (GOX0854) and the membrane-bound alcohol dehydrogenase (GOX1068)
      can competitively utilize glycerol but play no obvious roles in the biocatalyst
      preparation. Thus, the genes related to these two enzymes were deleted. Whole
      cells of G. oxydans ?GOX1068?GOX0854 can be prepared from glycerol with a 2.4
      fold higher biomass yield than that of G. oxydans 621H. Using whole cells of G.
      oxydans ?GOX1068?GOX0854 as the biocatalyst, 61.6 g L-1 xylonate was produced
      from 58.4 g L-1 xylose at a yield of 1.05 g g-1. CONCLUSION: This process is an
      example of efficient preparation of whole cells of G. oxydans with reduced cost.
      Besides xylonate production from xylose, other biocatalytic processes might also
      be developed using whole cells of metabolic engineered G. oxydans prepared from
      glycerol.

PMID- 30296951
TI  - Performing and analysing tone-induced cervical and ocular vestibular-evoked
      myogenic potentials in traumatic and non-traumatic vestibular pathology.
AB  - OBJECTIVE: This paper discusses our technique of carrying out cervical and ocular
      vestibular-evoked myogenic potential testing in a single position. The described
      technique allows for a symmetrical, natural flexion of the neck muscles, which is
      helpful as many of our patients have suffered traumatic deceleration injures.
      METHODS: Patients with suspected vestibular pathology referred by specialists
      were sequentially assessed in a tertiary referral neuro-otology unit within a
      teaching hospital using our technique and our previously established normative
      database. All patients underwent standardised vestibular assessment in addition
      to cervical and ocular vestibular-evoked myogenic potential assessment. Our
      normative data are in keeping with that reported by other centres. RESULTS: Many
      of the patients had abnormal vestibular-evoked myogenic potentials, which is in
      line with a history suggesting otolithic disease. CONCLUSION: Both cervical and
      ocular vestibular-evoked myogenic potentials offer several parameters for
      detecting abnormalities. The technique reported enables us to assess patients in
      an accurate fashion whether or not they have suffered traumatic neck injuries.

PMID- 30296952
TI  - Experiencing syndemic: disentangling the biosocial complexity of tuberculosis
      through qualitative research.
AB  - Tuberculosis (TB) remains a major global public health problem that has become a
      crisis fuelled by HIV and the increasing occurrence of antimicrobial resistance.
      What has been termed the biosocial nature of TB challenges effective control of
      the disease. Yet, biosocial interactions involved in the persistence of TB in
      diverse settings are difficult to systematically account for. The recently
      developed framework of syndemics provides a way to capture how complex health
      problems result from the interactions between diseases such as HIV and TB, and
      harmful social conditions such as unemployment, malnutrition and substance abuse.
      This article advances the syndemics scholarship by examining health conditions
      that cluster together with TB in the Russian Federation, by eliciting a set of
      social processes that precipitate this clustering and exacerbate health outcomes,
      and by analysing interactions between these health conditions and social
      processes. To provide an account of this complexity, the article takes a
      qualitative approach and draws on the perspectives and experiences of people with
      TB. The results demonstrate emergence of a syndemic of stress, substance abuse,
      TB and HIV that is sustained by poverty, occupational insecurity, marginalization
      and isolation. Frictions between the narrow focus of the health care system on TB
      and the wider syndemic processes in which the lives of many persons with TB are
      embedded, contribute to poorer health outcomes and increase the risks of
      developing drug resistance. Finally, the article argues that the large-scale and
      impersonal forces become embodied as individual pathology through the crucial
      interface of the ways in which persons experience and make sense of these forces
      and pathologies. Qualitative research is needed for the adequate analysis of this
      biosocial complexity in order to provide a solid basis for responses to TB
      centred syndemics in various settings.

PMID- 30296953
TI  - Peritonsillar infiltration of lidocaine with adrenaline is associated with
      increased risk of secondary post-tonsillectomy haemorrhage.
AB  - OBJECTIVES: In order to evaluate the safety of tonsillectomy among children, we
      retrospectively studied the incidence of post-operative complications, adverse
      events and their association with peri-operative medication. METHODS: Data were
      collected from the medical records of 691 patients aged 1-16 years, including
      details of post-operative complications (any unplanned contact with the
      hospital), analgesics, dexamethasone, 5-HT3 antagonists, local anaesthetic and
      haemostatic agents. RESULTS: Recovery was complicated in 13.6 per cent of
      patients, of whom 8.4 per cent were re-admitted to the ward. The most common
      complication was post-tonsillectomy haemorrhage, experienced by 7.1 per cent of
      patients. Re-operation under general anaesthesia (for grade III post
      tonsillectomy haemorrhage) was required by 4.2 per cent of patients.
      Peritonsillar infiltration of lidocaine with adrenaline increased the risk of
      post-tonsillectomy haemorrhage (odds ratio = 4.1; 95 per cent confidence interval
      = 2.1 to 8.3). CONCLUSION: Every seventh paediatric patient experienced a
      complicated recovery after tonsillectomy, caused by post-tonsillectomy
      haemorrhage in most cases. Local peritonsillar infiltration of lidocaine with
      adrenaline was associated with an increased risk of post-tonsillectomy
      haemorrhage.

PMID- 30296954
TI  - COST-EFFECTIVENESS OF INTERVENTIONS BASED ON PHYSICAL ACTIVITY IN THE TREATMENT
      OF CHRONIC CONDITIONS: A SYSTEMATIC LITERATURE REVIEW.
AB  - OBJECTIVES: The aim of this study is to review evidence on the cost-effectiveness
      of exercise-based interventions in the treatment of chronic conditions a decade
      after the publication of Roine et al. in 2009 (Roine E, Roine RP, Rasanen P, et
      al. Int J Technol Assess Health Care. 2009;25:427-454). METHODS: We carried out a
      review of published articles in PUBMED and JSTOR between January 1, 2008, and
      December 31, 2016. Full economic evaluations of exercise programs targeting
      patients with a chronic condition were eligible for inclusion. Data on program,
      design, and economic characteristics were extracted using a predefined extraction
      form. The quality of the economic evaluations was appraised using the adjusted
      Consensus Health Economic Criteria List. RESULTS: A total of 426 articles were
      identified and thirty-seven studies were selected. Eleven studies dealt with
      musculoskeletal and rheumatologic disorders, ten with cardiovascular diseases,
      six with neurological disorders, three with mental illnesses, three with cancers,
      and four with diabetes, respiratory diseases, or pelvic organ prolapse. In total,
      60 percent of exercise programs were dominant or cost-effective. For
      musculoskeletal and rheumatologic disorders, 72 percent of programs were dominant
      or cost-effective while this was the case for 57 percent of programs for
      cardiovascular diseases using a nonsurgical comparator. CONCLUSIONS: There is
      clear evidence in favor of exercise-based programs for the treatment of
      musculoskeletal and rheumatologic disorders and, to a lesser extent, for the
      treatment of cardiovascular diseases. More research is needed to evaluate the
      cost-effectiveness of physical activity in the treatment of neurological
      disorders, mental illnesses, cancers, respiratory diseases, and diabetes/obesity.

PMID- 30296955
TI  - Associations of birth characteristics with perimenopausal disorders: a
      prospective cohort study.
AB  - Perimenopausal disorders (PDs) are prevalent and importantly affect quality of
      life among middle-aged women. Yet, very little is known about the developmental
      origins of these disorders. The objective of this study was to investigate the
      associations of birth characteristics with PDs. This cohort study is based on
      archived birth records for birth weight and gestational age, and followed
      prospectively in Swedish inpatient and outpatient registers for 8 years (n=3212).
      The main outcomes were menopausal and climacteric states (e.g. flushing,
      sleeplessness), perimenopausal bleeding and other PDs (e.g. atrophic vaginitis).
      Cox proportional hazards regression models were used to estimate the hazard
      ratios (HRs) for three subtypes of PDs separately. During the follow-up, 218
      women had PDs, among whom 125 had menopausal and climacteric states, 61 had
      perimenopausal bleeding and 58 had other PDs as first recorded disorder. Birth
      weight was linearly associated with incidence rate of menopausal and climacteric
      states [HR=1.66 per 1 kg increase, 95% confidence interval (95% CI)=1.14-2.41].
      Gestational age (rather than birth weight) was associated with incidence rate of
      other PDs (HR=0.87 per 1 week increase, 95% CI=0.79-0.95). Neither birth weight
      nor gestational age was associated with perimenopausal bleeding. Similar results
      were found after adjustment for other early-life and adult socio-demographic
      characteristics. This observational study provides, for the first time, evidence
      regarding the developmental origins of PDs. Future research is required to
      investigate the underlying causal mechanisms, which may shed further light on the
      etiology of this class of disorders.

PMID- 30296956
TI  - Acceptable Limitations on Paramedic Duty to Treat During Disaster: A Qualitative
      Exploration.
AB  - : IntroductionThe Australian prehospital profession has not yet facilitated a
      comprehensive discussion regarding paramedic role and responsibility during
      disasters. Whether paramedics have a duty to treat under extreme conditions and
      what acceptable limitations may be placed on such a duty require urgent
      consideration. The purpose of this research is to encourage discussion within the
      paramedic profession and broader community on this important ethical and legal
      issue. METHODS: The authors employed qualitative methods to gather paramedic and
      community member perspectives in Victoria, Australia. RESULTS: These findings
      suggested that both paramedic and community member participants agree that
      acceptable limitations on paramedic duty to treat during disaster are required.
      These limitations should be based on consideration of the following factors:
      personal health circumstances (eg, pregnancy for female paramedics); pre-existing
      mental health conditions (eg, posttraumatic stress disorder/PTSD); competing
      personal obligations (eg, paramedics who are single parents); and unacceptable
      levels of personal risk (eg, risk of exposure and infection during a pandemic).
      CONCLUSION: It is only with the engagement of a more broadly representative
      segment of the prehospital profession and greater Australian community that
      appropriate guidance on limiting standards of care under extreme conditions can
      be developed and integrated within prehospital care in Australia. SmithE,
      BurkleFM Jr., GebbieK, FordD, BensimonC. Acceptable limitations on paramedic duty
      to treat during disaster: a qualitative exploration. Prehosp Disaster Med.
      2018;33(5):466-470.

PMID- 30296957
TI  - Dance interventions for people with dementia: systematic review and practice
      recommendations.
AB  - : ABSTRACTObjectives:Dance interventions are pleasant social activities that are
      often offered to people with dementia in care settings. Effectiveness of dance as
      a psychosocial intervention for people with dementia has been studied to some
      extent, but several methodological issues remain unexplored. This review aimed to
      analyze studies on dance interventions for people with dementia and to identify
      practice recommendations for the development of these interventions. METHODS: An
      electronic database search was run in December 2017 to identify records of dance
      interventions for people with dementia. We included all studies regardless of
      experimental design. Selected records were analyzed according to five criteria:
      study design and intentions of interventions; profile of participants and
      in/exclusion criteria; treatment indications and contraindications; description
      and performance of the interventions; and involved physical, cognitive,
      psychological, and social processes in dance. RESULTS: Fourteen records were
      included in which various study designs were observed. Description and
      performance of the interventions were well documented. Nine practice
      recommendations for implementing dance interventions were identified according to
      primary intentions of the intervention (therapeutic or recreational):
      indications; contra-indications; participant profile; dosage; session sequencing;
      setting of intervention; observance/attendance; contributors and facilitators;and
      assessments. CONCLUSIONS: Dance is a holistic intervention that can be
      implemented with a therapeutic or a leisure intention. Practice recommendations
      about dance interventions remain incomplete and insufficiently studied. Such
      recommendations could be helpful for clinicians to implement dance interventions
      in facilities where they work to better target people who could benefit from
      them, and for researchers to develop research in this field.

PMID- 30296958
TI  - The Impact of Irrational Beliefs on Paranoid Thoughts.
AB  - BACKGROUND: Although the ABC model proposed by cognitive behavioral theory has
      strong empirical support for a wide range of psychological problems, little is
      known about the role of irrational beliefs (IBs), a central concept of the ABC
      model, in the aetiology of paranoid thoughts, one of the most common psychotic
      symptoms. AIMS: The present study aimed to investigate the impact of IBs on
      paranoid thoughts and people's perceptions of others. METHOD: Eighty-one non
      clinical participants (m age = 21.21 years, SD = 2.72, range 18-33; 83.95%
      female) recruited for this study were randomly assigned to one of the two
      conditions: IBs or rational beliefs (RBs). In a role-play paradigm, subjects were
      asked to imagine holding a list of IBs or RBs, respectively, while being exposed
      to a neutral social context in a virtual reality environment. RESULTS: In line
      with the ABC model, results indicate that IBs lead to significantly higher levels
      of state paranoid thoughts and more negative perceptions of others than RBs, even
      after controlling for participants' baseline irrationality and trait paranoia [F
      (5,68) = 11.23, p < .001, Wilk's lambda = .54, partial eta2 = .45]. CONCLUSIONS:
      The findings of this paper suggest that IBs might play an aetiological role in
      the occurrence of paranoid thoughts. Practical and theoretical implications of
      these results are also considered.

PMID- 30296959
TI  - Improvement of gram-negative susceptibility to fluoroquinolones after
      implementation of a pre-authorization policy for fluoroquinolone use: A decade
      long experience.
AB  - OBJECTIVE: Due to concerns over increasing fluoroquinolone (FQ) resistance among
      gram-negative organisms, our stewardship program implemented a preauthorization
      use policy. The goal of this study was to assess the relationship between
      hospital FQ use and antibiotic resistance. DESIGN: Retrospective cohort. SETTING:
      Large academic medical center. METHODS: We performed a retrospective analysis of
      FQ susceptibility of hospital isolates for 5 common gram-negative bacteria:
      Acinetobacter spp., Enterobacter cloacae, Escherichia coli, Klebsiella
      pneumoniae, and Pseudomonas aeruginosa. Primary endpoint was the change of FQ
      susceptibility. A Poisson regression model was used to calculate the rate of
      change between the preintervention period (1998-2005) and the postimplementation
      period (2006-2016). RESULTS: Large rates of decline of FQ susceptibility began in
      1998, particularly among P. aeruginosa, Acinetobacter spp., and E. cloacae. Our
      FQ restriction policy improved FQ use from 173 days of therapy (DOT) per 1,000
      patient days to <60 DOT per 1,000 patient days. Fluoroquinolone susceptibility
      increased for Acinetobacter spp. (rate ratio [RR], 1.038; 95% confidence interval
      [CI], 1.005-1.072), E. cloacae (RR, 1.028; 95% CI, 1.013-1.044), and P.
      aeruginosa (RR, 1.013; 95% CI, 1.006-1.020). No significant change in
      susceptibility was detected for K. pneumoniae (RR, 1.002; 95% CI, 0.996-1.008),
      and the susceptibility for E. coli continued to decline, although the decline was
      not as steep (RR, 0.981; 95% CI, 0.975-0.987). CONCLUSIONS: A stewardship-driven
      FQ restriction program stopped overall declining FQ susceptibility rates for all
      species except E. coli. For 3 species (ie, Acinetobacter spp, E. cloacae, and P.
      aeruginosa), susceptibility rates improved after implementation, and this
      improvement has been sustained over a 10-year period.

PMID- 30296960
TI  - Assessment of the knowledge of Brazilian Community Health Workers regarding
      prenatal care.
AB  - : AimTo evaluate prenatal care knowledge of Brazilian community health workers
      (CHWs). BACKGROUND: Routine prenatal care is critical for reducing health risks
      in women and their children. One of the responsibilities of primary healthcare
      providers is the provision of prenatal care. The CHWs, with their frequent
      contact with populations, work to improve health outreach efforts and therefore
      may be key role players in prenatal care. METHODS: This was a cross-sectional
      study. A questionnaire was developed to ascertain the degree of knowledge
      regarding prenatal care of CHWs, including: (1) general responsibilities of CHWs;
      (2) the initial contact with a pregnant woman; (3) examinations and vaccinations
      recommended for pregnant women; (4) pregnancy complications and signs of labor;
      and (5) lifestyle considerations for pregnant women. Responses were categorized
      into levels for knowledge. Demographic data were also collected. Descriptive
      analyses were conducted. Proportions of subjects with different levels of
      knowledge were compared according to each demographic variable, separately for
      each block of knowledge, using the chi 2 and Fisher's exact tests.FindingsIn
      total, 194 CHWs were interviewed. Overall, the majority of the CHWs presented
      high levels of knowledge in blocks 1 (43%), 2 (59%) and 5 (83%). However, in
      block 3 the proportions of subjects with high levels of knowledge regarding
      examinations and vaccinations were 35 and 40%, respectively. Only 24% of the
      participants presented a high level of knowledge in block 4. Stratified data
      analyses suggest that females were statistically more likely to have high levels
      of knowledge, whereas no statistically significant differences were found for the
      other demographic variables. Health services are already routinely using the
      questionnaire. CONCLUSION: The results suggest that CHWs, especially female CHWs,
      have an important role in assisting pregnant women in the community. The study
      indicates the areas of knowledge that require more specific attention from
      training providers.

PMID- 30296961
TI  - Monitoring the Health of Public Health Responders: Development and Use of the
      Responder Safety, Tracking, and Resilience System (R-STaR) for Hurricane Matthew.
AB  - ABSTRACTOn October 7, 2016, Hurricane Matthew traveled along the coasts of
      Florida, Georgia, and South Carolina causing flooding and power outages. The
      Georgia Department of Public Health (DPH) developed the Web-based Responder
      Safety, Tracking, and Resilience (R-STaR) system to monitor the health and safety
      of public health responders and to inform disaster response planning for
      Hurricane Matthew. Using R-STaR, responders (n = 126) were e-mailed a daily
      survey while deployed to document injuries or harmful exposures and a post
      deployment survey on their post-deployment health and satisfaction with using R
      STaR. DPH epidemiologists contacted responders reporting injuries or exposures to
      determine the need for medical care. Frequencies were tabulated for quantitative
      survey responses, and qualitative data were summarized into key themes. Five
      percent (6/126) of responders reported injuries, and 81% (43/53) found R-STaR
      easy to use. Suggestions for R-STaR improvement included improving accessibility
      using mobile platforms and conducting pre-event training of responders on R-STaR.
      Lessons learned from R-STaR development and evaluation can inform the development
      and improvement of responder health surveillance systems at other local and state
      health departments and disaster and emergency response agencies. (Disaster Med
      Public Health Preparedness. 2018;page 1 of 8).

PMID- 30296962
TI  - Fertilization, hatching, and embryogenesis of diploid and triploid eggs of Anabas
      testudineus (Bloch, 1792).
AB  - SummaryThis study investigated the breeding parameters and embryogenic
      development of diploid and heat shock-induced triploid eggs of Anabas testudineus
      (Bloch, 1792). To this effect, broodstocks of A. testudineus were induced to
      spawn using the Ovaprim(r) hormone. After fertilization, the eggs were divided
      into two groups and one portion heat shocked at 41 degrees C (for 3 min), at
      approximately 4 min after fertilization. Results of fertilization, hatchability,
      as well as the sequence and timing of embryogenic development were collated from
      three breeding trials. Fertilization percentages were similar in both treatments
      (~90%) while hatchability was higher in the diploid eggs (79.56%) than the
      triploid induced eggs (50.04%). Both treatments had the same sequence of
      embryogenetic stages; however, the timing of development was significantly
      delayed in the triploids (i.e. beyond the 2-cell stages) as compared with the
      observations in the control group (diploid eggs). Consequently, hatching time was
      5 h faster in the diploid eggs [i.e. 18 hours post fertilization (hpf)] compared
      with the triploid induced eggs (23 hpf). The most critical stage of embryonic
      development in which mass mortality occurred in the different treatments was the
      somite stage. The status of triploid hatchlings was affirmed using erythrocyte
      morphology in 2-month-old fingerlings.

PMID- 30296963
TI  - The learning ability and memory retention of broiler breeders: 1 effects of
      reduced balanced protein diet on reward based learning.
AB  - Learning and mental abilities of farm animals are important for their adaptation
      to new environments and could serve as an indicator for welfare and performance.
      This study assessed the learning ability and memory retention of broiler breeders
      through a T-maze test with a reward v. no reward set-up. Feed supplemented with
      or without meal worms served as a reward. Two trials were conducted with either
      parent stock (PS) breeders or pure line A (PL) breeders and with the same dietary
      treatment namely a control (C) group fed with standard commercial diets and a
      reduced balanced protein (RP) group fed with RP diets (25% reduction of CP and
      amino acids). To maintain similar target BW, the RP group received on average 10%
      more feed. A tonic immobility (TI) test was performed to estimate the fearfulness
      of PS breeders. Most breeders were capable of completing the T-maze tests, but
      the C group needed less time compared with the RP group when their own feed was
      given as a reward. However, when meal worms were provided as an extra incentive,
      the RP group completed the maze significantly faster than the C group. Compared
      to the C breeders, the RP breeders remained longer in a TI state, indicating a
      higher level of fearfulness. Long-term memory retention in the T-maze test was
      observed in both groups. It is concluded that the RP diet had no influences on
      the learning ability of the reward v. no reward discrimination test and its
      memory retention of broiler breeders. The increased amount of time the RP
      breeders needed to solve the test was probably due to a higher sense of fear.
      Furthermore, the RP diet enhanced the motivation of breeders to obtain an
      alternative feed such as meal worms.

PMID- 30296964
TI  - Prevalence thresholds for wasting, overweight and stunting in children under 5
      years.
AB  - OBJECTIVE: Prevalence ranges to classify levels of wasting and stunting have been
      used since the 1990s for global monitoring of malnutrition. Recent developments
      prompted a re-examination of existing ranges and development of new ones for
      childhood overweight. The present paper reports from the WHO-UNICEF Technical
      Expert Advisory Group on Nutrition Monitoring. DESIGN: Thresholds were developed
      in relation to sd of the normative WHO Child Growth Standards. The international
      definition of 'normal' (2 sd below/above the WHO standards median) defines the
      first threshold, which includes 2.3 % of the area under the normalized
      distribution. Multipliers of this 'very low' level (rounded to 2.5 %) set the
      basis to establish subsequent thresholds. Country groupings using the thresholds
      were produced using the most recent set of national surveys. SETTING: One hundred
      and thirty-four countries. SUBJECTS: Children under 5 years. RESULTS: For wasting
      and overweight, thresholds are: 'very low' (~6 times 2.5 %). For stunting,
      thresholds are: 'very low' (~12 times 2.5 %). CONCLUSIONS: The proposed
      thresholds minimize changes and keep coherence across anthropometric indicators.
      They can be used for descriptive purposes to map countries according to severity
      levels; by donors and global actors to identify priority countries for action;
      and by governments to trigger action and target programmes aimed at achieving
      'low' or 'very low' levels. Harmonized terminology will help avoid confusion and
      promote appropriate interventions.

PMID- 30296965
TI  - Forty years on from Alma Ata: present and future of Primary Health Care research.

PMID- 30296966
TI  - Implications of Brexit on the effectiveness of the UK soft drinks industry levy
      upon CHD in England: a modelling study.
AB  - OBJECTIVE: An industry levy on sugar-sweetened beverages (SSB) was implemented in
      the UK in 2018. One year later, Brexit is likely to change the UK trade regime
      with potential implications for sugar price. We modelled the effect of potential
      changes in sugar price due to Brexit on SSB levy impacts upon CHD mortality and
      inequalities. DESIGN: We modelled a baseline SSB levy scenario; an SSB levy under
      'soft' Brexit, where the UK establishes a free trading agreement with the EU; and
      an SSB levy under 'hard' Brexit, in which World Trade Organization tariffs are
      applied. We used the previously validated IMPACT Food Policy model and
      probabilistic sensitivity analysis to estimate the effect of each scenario on CHD
      deaths prevented or postponed and life-years gained, stratified by age, sex and
      socio-economic circumstance, in 2021. SETTING: England. SUBJECTS: Adults aged 25
      years or older. RESULTS: The SSB levy was associated with approximately 370 (95 %
      uncertainty interval 220, 560) fewer CHD deaths and 4490 (2690, 6710) life-years
      gained in 2021. Associated reductions in CHD mortality were 4 and 8 % greater
      under 'soft' and 'hard' Brexit scenarios, respectively. The SSB levy was
      associated with approximately 110 (50, 190) fewer CHD deaths in the most deprived
      quintile compared with 60 (20, 100) in the most affluent, under 'hard' Brexit.
      CONCLUSIONS: Our study found the SSB levy resilient to potential effects of
      Brexit upon sugar price. Even under 'hard' Brexit, the SSB levy would yield
      benefits for CHD mortality and inequalities. Brexit negotiations should deliver a
      fiscal and regulatory environment which promotes population health.

PMID- 30296967
TI  - Recent strategies for the diagnosis of early Lyme disease.
AB  - Lyme disease (LD) is the most common tick-borne disease in the Northern
      Hemisphere. As the most prevalent vector-borne disease in the USA, LD affects
      300,000 human cases each year. LD is caused by inoculation of the bacterial
      spirochete, Borrelia burgdorferi sensu lato, from an infected tick. If not
      treated quickly and completely, the bacteria disseminate from the tick's biting
      site into multiple organs including the joints, heart, and brain. Thus, the best
      outcome from medical intervention can be expected with early detection and
      treatment with antibiotics, prior to multi-organ dissemination. In the absence of
      a characteristic rash, LD is diagnosed using serological testing involving enzyme
      linked immunosorbent assay (ELISA) followed by western blotting, which is
      collectively known as the two-tier algorithm. These assays detect host antibodies
      against the bacteria, but are hampered by low sensitivity, which can miss early
      LD cases. This review discusses the application of some current assays for
      diagnosing LD clinically, thus providing a foundation for exploring newer
      techniques being developed in the laboratory for more sensitive detection of
      early LD.

PMID- 30296968
TI  - Evolution of macromolecular structure: a 'double tale' of biological accretion
      and diversification.
AB  - The evolution of structure in biology is driven by accretion and diversification.
      Accretion brings together disparate parts to form bigger wholes. Diversification
      provides opportunities for growth and innovation. Here, we review patterns and
      processes that are responsible for a 'double tale' of accretion and
      diversification at various levels of complexity, from proteins and nucleic acids
      to high-rise building structures in cities. Parts are at first weakly linked and
      associate variously. As they diversify, they compete with each other and are
      selected for performance. The emerging interactions constrain their structure and
      associations. This causes parts to self-organise into modules with tight linkage.
      In a second phase, variants of the modules evolve and become new parts for a new
      generative cycle of higher-level organisation. Evolutionary genomics and network
      biology support the 'double tale' of structural module creation and validate an
      evolutionary principle of maximum abundance that drives the gain and loss of
      modules.

PMID- 30296969
TI  - Early life nutrition.
AB  - Nutritionally, the first 1,000 days of an infant's life - from conception to two
      years - has been identified as a highly influential period, during which lasting
      health can be achieved. Significant evidence links patterns of infant feeding to
      both short and long-term health outcomes, many of which can be prevented through
      nutritional modifications. Recommended globally, breastfeeding is recognised as
      the gold standard of infant nutrition; providing key nutrients to achieve optimal
      health, growth and development, and conferring immunologic protective effects
      against disease. Nevertheless, infant formulas are often the sole source of
      nutrition for many infants during the first stage of life. Producers of infant
      formula strive to supply high quality, healthy, safe alternatives to breast milk
      with a comparable balance of nutrients to human milk imitating its composition
      and functional performance measures. The concept of 'nutritional programming',
      and the theory that exposure to specific conditions, can predispose an
      individual's health status in later life has become an accepted dictum, and has
      sparked important nutritional research prospects. This review explores the impact
      of early life nutrition, specifically, how different feeding methods affect
      health outcomes.

PMID- 30296970
TI  - Use of contrast-enhanced magnetic resonance imaging of the pelvis to describe
      changes at different anatomic sites which are potentially specific for
      polymyalgia rheumatica.
AB  - OBJECTIVES: To identify inflammatory pelvic structures of patients with
      polymyalgia rheumatica (PMR) by magnetic resonance imaging (MRI) in detail,
      searching for a disease-specific pattern. METHODS: A total of 40 contrast
      enhanced pelvic MRIs of patients with a clinical diagnosis of PMR was reviewed by
      an experienced musculoskeletal radiologist who assessed all abnormalities semi
      quantitatively, based on a predefined scoring system. RESULTS: The median
      (25th/75th percentiles) age of patients was 67 (55/73) years, median symptom
      duration 13 (6/22) weeks, 55% female, median CRP 1.9 (0.7/4) mg/dl, median ESR
      30/1h (17/43). Ten patients were diagnosed with rheumatoid arthritis (25%), in
      addition to their leading polymyalgic symptom. Multi-locular, mostly bilateral,
      peritendinous enhancement of pelvic girdle tendons was found to be the hallmark
      of PMR in all patients. Low-grade hip synovitis was also detected frequently. In
      all cases, >=4 extracapsular tendinous sites were bilaterally affected. Besides
      involvement of the common ischiocrural tendon and the glutaeus medius and minimus
      tendon (present in all cases), an enhancement of the proximal rectus femoris
      origin was observed in 100% and of the adductor muscles at the inferior medial
      pubic bone in 90% of cases. The observed MRI pattern patho-anatomically suggests
      inflammation of the external peritendineum. CONCLUSIONS: The uniformity of the
      observed pelvic inflammatory pattern detected by contrast-enhanced MRI in PMR
      patients suggests that it may become relevant for diagnostic purposes. The
      bilateral involvement of at least 4 extracapsular sites (including the origins of
      proximal rectus femoris or adductorial muscles) appears to be characteristic of
      PMR.

PMID- 30296971
TI  - Imaging of axial spondyloarthritis. New aspects and differential diagnoses.
AB  - Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by
      inflammatory back pain and several other disease manifestations and
      comorbidities. The 2009 ASAS classification criteria differentiate between the
      classical ankylosing spondylitis or radiographic axSpA and non-radiographic axSpA
      based on the presence or absence of definite radiographic changes in the
      sacroiliac joints. Importantly, back pain in patients with axSpA may well have
      reasons other than axial inflammation or new bone formation. There are several
      important differential diagnoses such as diffuse idiopathic skeletal hyperostosis
      and osteitis condensans. This review summarises recent publications concerning
      the performance of imaging modalities in the field, such as conventional
      radiography, magnetic resonance imaging, computed tomography and dual energy x
      ray absorptiometry including the trabecular bone score.

PMID- 30296972
TI  - Imaging of joints in systemic lupus erythematosus.
AB  - Musculoskeletal symptoms are among the most common manifestations in patients
      with systemic lupus erythematosus (SLE), being reported in up to 95% of patients;
      joint and tendon involvement can range from arthralgia to severe deforming
      arthropathy; while myositis a rare manifestation, comorbid fibromyalgia is
      reported in up to 40% of SLE patients. All these manifestations have a
      significant impact on the patients' quality of life, possibly leading to
      disability and functional impairment in daily living activities. In recent years,
      thanks to the availability of new imaging techniques for the assessment of tendon
      and joint pathologies, the approach to the definition and characterisation of
      these manifestations in SLE is constantly evolving. In this review we will
      therefore illustrate the state of the art of imaging techniques in the assessment
      of joint involvement in SLE, focusing on ultrasounds (US) and magnetic resonance
      (MRI), discussing their advantages, drawbacks and possible future developments.
      The main findings that emerge from the recent literature is that imaging studies
      may allow a more accurate definition of disease subtypes revealing an unexpected
      higher prevalence of joint and tendon involvement with respect to what known by
      clinical evaluation and standard radiography. Indeed, US and MRI also made
      possible the identification of joints and tendons pathologies in patients with no
      or very mild clinical symptoms. On the other hand, the interpretation of some
      findings remains uncertain, as well as the validity and feasibility of this
      analysis in clinical practice. Thus, further studies should clarify the clinical
      meaning of subclinical abnormalities detected in US and MRI scans and their
      impact on the long-term outcomes.

PMID- 30296973
TI  - Imaging detected tenosynovitis of metacarpophalangeal and wrist joints: an
      increasingly recognised characteristic of rheumatoid arthritis.
AB  - Tenosynovitis is traditionally recognised at physical examination in patients
      with inflammatory rheumatic diseases, such as, e.g. psoriatic arthritis and
      (longstanding) rheumatoid arthritis (RA). The increasing use of sensitive imaging
      techniques (ultrasound, magnetic resonance imaging (MRI)) has recently revealed
      that subclinical tenosynovitis is prevalent in early RA and in patients in
      different phases of RA development (asymptomatic state, arthralgia, early
      arthritis). In this review, the recent findings on MRI-detected tenosynovitis and
      associations with RA development are highlighted, and an overview of the most
      reported inflamed tendon locations within the hand and wrist of patients in
      different disease phases is provided. The data presented show that tenosynovitis
      is one of the earliest inflammatory features in patients with imminent RA and
      associated with impairment of activities in daily life. The value of
      tenosynovitis as an outcome measure in RA is also discussed.

PMID- 30296974
TI  - Update on magnetic resonance imaging and ultrasound in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) disease activity often remains difficult to assess and
      quantify accurately. As a result, numerous measures using various techniques to
      estimate clinical activity have been developed for clinical research and care.
      More objective imaging biomarkers for early detection and accurate, quantitative
      measurement of the disease burden are therefore of interest both for clinical use
      and for investigational studies. Two widely studied imaging biomarkers are
      magnetic resonance imaging (MRI) and ultrasound (US), imaging tests that are
      increasingly available to clinicians. While substantial and increasing evidence
      has been reported that these tools are valid and provide advantages in both
      clinical trials and clinical assessments, more information is needed to inform
      their appropriate use in routine clinical care. The goals of this review are to
      outline the current literature regarding each of these objective imaging tools,
      assess their strengths and limitations, and to clarify knowledge gaps to be
      filled before these techniques may be more optimally utilised.

PMID- 30296975
TI  - The use of ultrasound in the management of large-vessel vasculitis: an evolving
      concept.
AB  - Imaging is increasingly recognised as an essential element in the management of
      several rheumatologic conditions. Ultrasound is in widespread use as a safe,
      reproducible, and directly interpretable method for diagnosis and evaluation of
      arthritis and increasingly of large-vessel vasculitis (LVV). Indeed, the
      diagnosis and management of LVV are being transformed through the use of imaging.
      Increasing and more standardised evidence is being produced on the role of colour
      duplex sonography in the management of LVV. Nonetheless, some controversies and
      unresolved issues remain. This review describes current findings and reviews
      future perspectives in the use of ultrasound for the diagnosis and management of
      LVV.

PMID- 30296976
TI  - MRI in imaging of rheumatic diseases: an overview for clinicians.
AB  - Magnetic resonance imaging (MRI) is a technique that utililises powerful magnets
      and radiofrequency to produce 3-dimentional images. MRI does not involve ionising
      radiation and has superb tissue resolution, enabling excellent delineation of
      anatomy as well as pathology in joints. This article briefly reviews the
      technical principle of magnetic resonance and discusses advantages and
      disadvantages of the technique, with particular attention to rheumatologic
      imaging. New information is summarised concerning the use of contrast media,
      dynamic, contrast-enhanced MRI, diffusion-weighted imaging, cartilage imaging and
      whole-body MRI.

PMID- 30296977
TI  - Enthesitis detection by ultrasound: where are we now?
AB  - Over the last 25 years, ultrasound has been used to evaluate involvement at the
      entheses in spondyloarthritis (SpA) and psoriatic arthritis (PsA). Several
      studies have been reported indicating its value in detecting active inflammation
      at entheseal sites using both gray scale and Doppler findings. This review
      explores the recent literature and appraises the current knowledge and the unmet
      needs of enthesitis detection by ultrasound in the management of both SpA and
      PsA.

PMID- 30296978
TI  - The peripheral nerves: update on ultrasound and magnetic resonance imaging.
AB  - The motor and sensory branches of the somatic peripheral nervous system (PNS) can
      be visualised by different imaging systems. This article focuses on imaging of
      peripheral nerves by magnetic resonance imaging (MRI) and high-resolution
      ultrasound (US). The anatomic basis of the peripheral nerve image, common
      pathologies and clinical value of US and MRI imaging of peripheral nerves are
      reviewed.

PMID- 30296979
TI  - Update on imaging in gout: contrasting and comparing the role of dual-energy
      computed tomography to traditional diagnostic and monitoring techniques.
AB  - In this systematic literature review, we update imaging modalities in gout, with
      a focus on newer technologies, particularly Dual-energy computed tomography
      (DECT). Conventional radiography (CR), ultrasonography (US), magnetic resonance
      imaging (MRI), computed tomography (CT) and dual-energy CT (DECT) have been used
      to evaluate different stages and clinical manifestations of gout and
      hyperuricaemia. We compare and contrast these modalities across the spectrum of
      this disease and of clinical scenarios and objectives (1).

PMID- 30296980
TI  - Update on imaging in rheumatic diseases.

PMID- 30296981
TI  - Update on imaging in rheumatic diseases: cartilage.
AB  - In recent years, the role of articular cartilage for understanding pathogenesis
      as well as for clinical research has become increasingly important. Whereas
      previously cartilage could only be assessed invasively, various imaging
      procedures are available for its evaluation now. Although still widely used,
      conventional radiography bears significant limitations since it assesses
      cartilage indirectly by joint space width. Today, the cartilage thickness and
      structure can be reliably evaluated using ultrasound, although the molecular
      structure cannot be determined, yet. Besides ultrasound, MRI offers the
      possibility to image morphological changes with a very high resolution. In
      addition, the quality and composition of joint cartilage can already be measured
      due to a constant technical improvement and new MRI sequences such as dGEMRIC
      even in small joints (e.g. MCP or MTP joints). Despite the advantages of contrast
      agents for the detection of inflammation, its use is reevaluated today. Regarding
      that contrast agent-free imaging techniques for the assessment of joint cartilage
      are developed with great effort to depict its quality and changes over time.
      These novel MRI methods such as T2/T2*- and T1rho-mapping, gagCEST, and sodium
      imaging provide promising quantitative imaging biomarkers that can detect early
      cartilage changes before morphological alterations occur. Hence, US and MRI will
      likely be of paramount importance in future clinical trials and clinical
      assessment of inflammatory and degenerative joint diseases not only for
      understanding pathogenesis but also for using its possible value in daily
      practice.

PMID- 30296982
TI  - The role of imaging in evaluating patients with idiopathic inflammatory
      myopathies.
AB  - OBJECTIVES: To describe imaging modalities for diagnosing and monitoring of
      patients with idiopathic inflammatory myopathies. METHODS: A detailed literature
      search summarising recent data documenting the contribution of different imaging
      techniques to current management of idiopathic inflammatory myopathies was
      performed. RESULTS: An overview of methods most frequently used for evaluation of
      inflammatory myopathies and the description of their role in the diagnostic and
      monitoring process is presented. CONCLUSIONS: MRI is currently the most useful
      method capable of demonstrating both inflammatory and post-inflammatory changes
      in the muscles and surrounding soft tissue. Several studies have documented
      potential usefulness of other imaging techniques, such as ultrasonography,
      positron emission tomography, scintigraphy, and dual-energy x-ray absorptiometry.

PMID- 30296983
TI  - Ultrasonography in gout: utility in diagnosis and monitoring.
AB  - The use of ultrasonography has a considerable potential for diagnosis and
      monitoring of gout due to its capacity to detect urate crystal deposits in
      joints, e.g. on the cartilage surface, visualised as the double contour sign, and
      in soft tissues, e.g. as tophi. Furthermore, ultrasonography can visualise both
      synovitis and bone erosion. Consensus-based definitions for ultrasonographic
      elementary lesions in gout were validated in 2015, and ultrasonography is already
      included in the 2015 ACR/EULAR classification criteria for gout. This report
      evaluates the current literature on the use of ultrasonography for diagnosing and
      monitoring gout.

PMID- 30296984
TI  - Recent advances in research imaging of osteoarthritis with focus on MRI,
      ultrasound and hybrid imaging.
AB  - For imaging of osteoarthritis (OA), MRI plays a major role in the research
      setting, with compositional MRI techniques becoming increasingly more important
      thanks to their capacity to assess 'premorphologic' biochemical compositional
      changes of articular and periarticular tissues. Although radiography remains the
      primary imaging modality in OA clinical trials, known limitations for
      visualisation of OA features significantly limits the utility of radiography both
      clinically and in the research arena. Compositional MRI techniques can
      potentially supplement routine clinical MRI sequences to identify cartilage
      degeneration at an earlier stage when radiographs may be normal. Ultrasound can
      be a useful adjunct to radiography and MRI particularly for evaluation of hand OA
      and for the evaluation of synovitis. Emerging hybrid imaging techniques including
      PET/MRI and PET/CT allow evaluation of the joint with simultaneous assessment of
      morphological changes and metabolic activities, showing a potential for these
      hybrid systems to play an increasing role in OA research.

PMID- 30296985
TI  - Magnetic resonance imaging and magnetic resonance angiography in large-vessel
      vasculitides.
AB  - The role of imaging in diagnosis and monitoring of vasculitides has steadily
      become more important during the last years. As a result of the technological
      progress, its low invasiveness and its relatively good diagnostic reliability,
      magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) are
      increasingly used in the assessment of vasculitic changes of extra- and intra
      cranial arteries. The aim of this review is to outline the significance of
      different imaging modalities, particularly the significance of MRI/MRA, in the
      context of large-vessel vasculitides, especially in regard to the first EULAR
      (The European League Against Rheumatism)-recommendations on the role of imaging
      in the process of diagnosis and monitoring of patients with suspected large
      vessel vasculitides. Furthermore, some typical imaging findings as well as the
      basics of MRI technique are to be presented.

PMID- 30296986
TI  - The role of cardiovascular magnetic resonance imaging in rheumatic heart disease.
AB  - Cardiovascular involvement is a well-known feature of inflammatory rheumatic
      diseases, although often clinically silent, so early cardiovascular involvement
      may remain unrecognised. Thus, increased awareness and improved insights into the
      pathomechanisms of heart disease in the context of inflammatory rheumatic disease
      has led to an emerging role of cardiovascular magnetic resonance (CMR) as an
      accurate and non-invasive diagnostic test for detection of early (as well as
      late) cardiovascular involvement in inflammatory rheumatic disease. The present
      article will review the current potential as well as the limitations of
      established and emerging, qualitative and quantitative CMR techniques in the
      setting of inflammatory rheumatic disease and shed some light onto current
      developments in the field.

PMID- 30296987
TI  - Overview of musculoskeletal ultrasound for the clinical rheumatologist.
AB  - Within the realm of rheumatology, the field of musculoskeletal ultrasound (MSUS)
      has grown exponentially over the last few decades. This review, aimed at the
      clinical rheumatologist, provides a basic overview of the principles of image
      generation and the commonly used clinical applications of MSUS, while also
      highlighting its advantages and limitations. In particular, the role of MSUS in
      the assessment of early and established rheumatoid arthritis, crystalline
      disease, the spondyloarthropathies and Sjogren's disease is discussed in more
      detail and by reviewing the pertinent literature.

PMID- 30296988
TI  - Imaging in peripheral and axial psoriatic arthritis: contributions to diagnosis,
      follow-up, prognosis and knowledge of pathogenesis.
AB  - Imaging in psoriatic arthritis (PsA) is rapidly evolving, and the use of
      sensitive modalities both in clinical research and routine care is increasing.
      This article provides an overview of current knowledge of different imaging
      methods in PsA, including current and possible future use in diagnosis, prognosis
      and clinical management, value in understanding pathogenesis, and latest
      activities to establish responsive imaging outcome measures. Much research
      remains to be performed concerning imaging in PsA, particularly on its optimal
      use in routine clinical care, the clinical consequences of imaging-detected
      subclinical disease, and specific and sensitive PsA imaging outcome measures.

PMID- 30296989
TI  - The role of 18F-FDG positron emission tomography for the diagnosis of
      vasculitides.
AB  - Large-vessel vasculitis is the most common form of primary vasculitis comprising
      cranial and large-vessel giant cell arteritis, Takayasu's arteritis and
      idiopathic aortitis. Prompt diagnosis and treatment of large-vessel vasculitis
      are important to prevent potentially serious emergencies such as visual loss,
      vascular stenosis and aneurysm formation. Temporal artery biopsy has long been
      the standard for diagnosing GCA - an invasive technique that lacks sensitivity
      compared to a clinical diagnosis that relies on a combination of clinical
      symptoms, elevated serum inflammatory markers and imaging findings. Conventional
      angiography focussing on the detection of arterial stenoses and occlusion does
      not assess vessel wall changes. Therefore, angiography is being increasingly
      replaced by newer imaging modalities such as magnetic resonance imaging and 18F
      FDG positron emission tomography-computed tomography. However, imaging modalities
      also including ultrasound are not uniformly used for diagnosis and monitoring of
      large-vessel vasculitis in clinical practice. Very recently recommendations for
      imaging have been developed by the European League Against Rheumatism and the
      Society of Nuclear Medicine and Molecular Imaging in cooperation with the
      European Association of Nuclear Medicine and an interest group endorsed by the
      American Society of Nuclear Cardiology. These and a small literature search using
      PubMed are the basis for this review.

PMID- 30296990
TI  - The use of ultrasound for assessing interstitial lung involvement in connective
      tissue diseases.
AB  - Interstitial lung disease (ILD) is one of the most serious pulmonary
      complications associated with connective tissue diseases (CTDs), resulting in
      significant morbidity and mortality. Recently, lung ultrasound examination has
      appeared as a useful, feasible, non-invasive, radiation-free imaging technique
      with high sensitivity and specificity for the diagnosis of CTD-associated ILD. In
      this review, we discuss the literature concerning lung ultrasound findings (B
      lines and pleural irregularities) in systemic sclerosis. We also examine the
      possible utility and potential limitations of lung ultrasound in other CTDs
      including: inflammatory myopathies, mixed connective tissue disease, and
      Sjogren's syndrome. Specifically, we compare the diagnostic accuracy of lung
      ultrasound with traditional imaging techniques and pulmonary functional tests.

PMID- 30296991
TI  - Advances in salivary gland ultrasonography in primary Sjogren's syndrome.
AB  - Salivary gland ultrasonography (US) has recently been re-discovered as a useful
      tool to assess salivary gland involvement in primary Sjogren's syndrome (SS). In
      this review, we discuss US of the major salivary glands in the diagnosis of
      primary SS and analyse the possible added value of inclusion in classification
      criteria. We review the literature concerning associations between US of the
      major salivary glands, salivary gland histology and serology, with the
      possibility that US may be of value in disease stratification. We also examine
      the possible utility for US to monitor patient response to therapy in both
      clinical research and standard clinical care.

PMID- 30296992
TI  - Functional MRI in rheumatic diseases with a focus on fibromyalgia.
AB  - Pain is the most common symptom in rheumatic diseases. However, the severity of
      pain does not correlate with pathology. The lack of an objective test for pain
      results in clinicians consider pain in patients with fibromyalgia as
      psychological. Research over the last two decade using functional neuroimaging
      especially functional MRI scan have demonstrated objectively that patients with
      fibromyalgia were not malingering. Pain processing is complex and multiple
      regions of the brain are involved. One consistent finding is decrease activity in
      regions of the brain involved in pain inhibitory pathways suggesting this is one
      of the fundamental pathophysiology processes in fibromyalgia.

PMID- 30296993
TI  - Current imaging techniques in osteoporosis.
AB  - Osteoporosis is a global pandemic affecting children, men and women of all ages
      and ethnicities. Millions of people suffer fragility fractures each year around
      the world as a result of this bone disease, which can have devastating
      consequences for them, including permanent disability and death. Many fractures
      are preventable by identifying people at high risk for fracture and falls, and
      diagnosing those who already have osteoporosis, before they fracture.
      Rheumatologists commonly encounter people with fragile bones, either as an
      isolated entity, or a co-morbidity to their underlying rheumatic illness or
      treatment. Imaging in osteoporosis can be used to make a diagnosis, while
      measurements of bone and body tissues, most commonly bone mineral density, can be
      used to identify those at risk and monitor them following treatment. Modern
      densitometry scanners may have multiple new features including measures of hip
      geometry, trabecular bone score, finite element analysis, fat and muscle mass,
      and may have additional imaging features including vertebral fracture assessment
      and atypical femoral fracture screening. When used correctly, these tools provide
      invaluable information for the assessment of the effectiveness of interventions
      in clinical studies, and patient management in clinical practice. In this article
      we review osteoporosis imaging techniques, with an emphasis on dual-energy x-ray
      absorptiometry, and how to apply and interpret them in modern rheumatology
      practice.

PMID- 30296995
TI  - The randomness that shapes our DNA.
AB  - Just 5% of the human genome is subject to neutral evolution, but this process
      remains central to understanding the history of human migration across the Earth.

PMID- 30296994
TI  - Personality links with lifespan in chimpanzees.
AB  - Life history strategies for optimizing individual fitness fall on a spectrum
      between maximizing reproductive efforts and maintaining physical health over
      time. Strategies across this spectrum are viable and different suites of
      personality traits evolved to support these strategies. Using data from 538
      captive chimpanzees (Pan troglodytes) we tested whether any of the dimensions of
      chimpanzee personality - agreeableness, conscientiousness, dominance,
      extraversion, neuroticism, and openness - were associated with longevity, an
      attribute of slow life history strategies that is especially important in
      primates given their relatively long lives. We found that higher agreeableness
      was related to longevity in males, with weaker evidence suggesting that higher
      openness is related to longer life in females. Our results link the literature on
      human and nonhuman primate survival and suggest that, for males, evolution has
      favored the protective effects of low aggression and high quality social bonds.

PMID- 30296997
TI  - Infective Endocarditis.
AB  - Infective endocarditis (IE) is an uncommon infection of cardiac valves associated
      with bacteremia. It increasingly affects elderly patients with chronic disease
      and artificial cardiac devices. The presentation, however, remains subtle and
      varied, with nonspecific symptoms ranging from those resembling a mild viral
      infection to septic shock and multiorgan failure. IE carries potential to cause
      significant morbidity and mortality through its impact on cardiac function and
      from embolic complications. Blood cultures prior to antibiotics and obtaining
      prompt echocardiography are key diagnostic steps, followed by proper selection of
      empiric antibiotics and, in many cases, collaboration with infectious disease,
      cardiology, and cardiothoracic surgery specialists.

PMID- 30296996
TI  - Oldest skeleton of a fossil flying squirrel casts new light on the phylogeny of
      the group.
AB  - Flying squirrels are the only group of gliding mammals with a remarkable
      diversity and wide geographical range. However, their evolutionary story is not
      well known. Thus far, identification of extinct flying squirrels has been
      exclusively based on dental features, which, contrary to certain postcranial
      characters, are not unique to them. Therefore, fossils attributed to this clade
      may indeed belong to other squirrel groups. Here we report the oldest fossil
      skeleton of a flying squirrel (11.6 Ma) that displays the gliding-related
      diagnostic features shared by extant forms and allows for a recalibration of the
      divergence time between tree and flying squirrels. Our phylogenetic analyses
      combining morphological and molecular data generally support older dates than
      previous molecular estimates (~23 Ma), being congruent with the inclusion of some
      of the earliest fossils (~36 Ma) into this clade. They also show that flying
      squirrels experienced little morphological change for almost 12 million years.

PMID- 30296998
TI  - Community-Acquired Pneumonia.
AB  - Community-acquired pneumonia is one of the most common infections seen in
      emergency department patients. There is a wide spectrum of disease severity and
      viral pathogens are common. After a careful history and physical examination,
      chest radiographs may be the only diagnostic test required. The first step in
      management is risk stratification, using a validated clinical decision rule and
      serum lactate, followed by early antibiotics and fluid resuscitation when
      indicated. Antibiotics should be selected with attention to risk factors for
      multidrug-resistant respiratory pathogens. Broad use of pneumococcal vaccine in
      adults and children can prevent severe community-acquired pneumonia.

PMID- 30296999
TI  - The Emergency Department Diagnosis and Management of Urinary Tract Infection.
AB  - Urinary tract infection (UTI) is a common infection seen in the emergency
      department. The spectrum of UTI includes simple versus complicated infection and
      lower versus upper UTI. No one history or examination finding is definitive for
      diagnosis. Testing often includes urinalysis and/or urine dipstick, and several
      pitfalls may occur in interpretation. Urine cultures should be obtained in
      complicated or upper UTIs but not simple and lower tract UTIs, unless a patient
      is pregnant. Imaging often is not required. Most patients with simple cystitis
      and pyelonephritis are treated as outpatients. A variety of potentially dangerous
      conditions may mimic UTI and pyelonephritis.

PMID- 30297000
TI  - Emergency Department Approach to the Patient with Suspected Central Nervous
      System Infection.
AB  - Central nervous system (CNS) infections require early recognition and aggressive
      management to improve patient survival and prevent long-term neurologic sequelae.
      Although early detection and treatment are important in many infectious
      syndromes, CNS infections pose unique diagnostic and therapeutic challenges. The
      nonspecific signs and symptoms at presentation, lack of characteristic infectious
      changes in laboratory and imaging diagnostics, and closed anatomic and
      immunologically sequestered space each present challenges to the emergency
      physician. This article proposes an approach to the clinical evaluation of
      patients with suspected CNS infection and highlights methods of diagnosis,
      treatment, and complications associated with CNS infections.

PMID- 30297001
TI  - Skin and Soft Tissue Infections in the Emergency Department.
AB  - This article covers the diagnosis and treatment of skin and soft tissue
      infections commonly encountered in the emergency department: impetigo, cutaneous
      abscesses, purulent cellulitis, nonpurulent cellulitis, and necrotizing skin and
      soft tissue infections. Most purulent infections in the United States are caused
      by methicillin-resistant Staphylococcus aureus. For abscesses, we emphasize the
      importance of incision and drainage. Nonpurulent infections are usually caused by
      streptococcal species and initial empiric antibiotics need not cover methicillin
      resistant Staphylococcus aureus. For uncommon but potentially lethal necrotizing
      skin and soft tissue infections, the challenge is rapid diagnosis in the
      emergency department and prompt surgical exploration and debridement.

PMID- 30297003
TI  - Management of Patients with Sexually Transmitted Infections in the Emergency
      Department.
AB  - Sexually transmitted infections (STI) are very common infections in the United
      States. Most patients with STIs are evaluated and treated in primary care
      settings; however, many also present to the Emergency Department (ED) for initial
      care. Management of STIs in the ED includes appropriate testing and treatment per
      CDC Sexually Transmitted Diseases Treatment Guidelines. Although most patients
      with STIs are asymptomatic or may only exhibit mild symptoms, serious
      complications from untreated infection are possible. Pregnant women with STIs are
      particularly vulnerable to serious complications; therefore, empiric ED treatment
      combined with close follow-up care and referral to obstetrics are paramount.

PMID- 30297004
TI  - Management of Human Immunodeficiency Virus in the Emergency Department.
AB  - Over the past 30 years, significant advances have transformed the landscape of
      human immunodeficiency virus (HIV) care in the emergency department. Diagnosis
      and management of HIV has improved, resulting in a decline in the incidence of
      acquired immunodeficiency syndrome (AIDS)-defining infections. Advances in
      pharmacology have led to fewer serious medication toxicities and more tolerable
      regimens. Emergency providers have played an increasingly important role in HIV
      screening and diagnosis of acute infection. Provision of postexposure prophylaxis
      is expanding from a focus on occupational exposure to include all high-risk
      cases.

PMID- 30297002
TI  - Musculoskeletal Infections in the Emergency Department.
AB  - Bone and joint infections are potentially limb-threatening or even life
      threatening diseases. Emergency physicians must consider infection when
      evaluating musculoskeletal complaints, as misdiagnosis can have significant
      consequences. Patients with bone and joint infections can have heterogeneous
      presentations with nonspecific signs and symptoms. Staphylococcus aureus is the
      most commonly implicated microorganism. Although diagnosis may be suggested by
      physical examination, laboratory testing, and imaging, tissue sampling for Gram
      stain and microbiologic culture is preferable, as pathogen identification and
      susceptibility testing help optimize long-term antibiotic therapy. A combination
      of medical and surgical interventions is often necessary to effectively manage
      these challenging infections.

PMID- 30297005
TI  - Infectious Disease Emergencies in Oncology Patients.
AB  - Oncology patients are a unique patient population in the emergency department
      (ED). Malignancy and associated surgical, chemotherapeutic, or radiation
      therapies put them at an increased risk for infection. The most ominous
      development is neutropenic fever, which happens often and may not present with
      signs or symptoms other than fever. A broad differential diagnosis is essential
      when considering infectious disease pathology in both neutropenic and non
      neutropenic oncology patients in the ED.

PMID- 30297007
TI  - Biothreat Agents and Emerging Infectious Disease in the Emergency Department.
AB  - The challenges faced by the emergency physician with recognizing and treating
      category A biothreat agents and emerging infectious disease are summarized and
      reviewed.

PMID- 30297006
TI  - Approach to Transplant Infectious Diseases in the Emergency Department.
AB  - The emergency department (ED) is an increasingly important site of care for
      patients who have undergone solid organ transplantation or hematopoietic cell
      transplantation. It is paramount for emergency physicians to recognize infections
      early on, obtain appropriate diagnostic testing, initiate empirical antimicrobial
      therapy, and consider specialty consultation and inpatient admission when caring
      for these patients. This review provides emergency physicians with an approach to
      the assessment of transplant patients' underlying risk for infection, formulation
      of a broad differential diagnosis, and initial management of transplant
      infectious disease emergencies in the ED.

PMID- 30297009
TI  - Antimicrobial Stewardship in the Emergency Department.
AB  - The emergency department (ED) is the hub of the US health care system. Acute
      infectious diseases are frequently encountered in the ED setting, making this a
      critical setting for antimicrobial stewardship efforts. Systems level and
      behavioral stewardship interventions have demonstrated success in the ED setting
      but successful implementation depends on institutional support and the presence
      of a physician champion. Antimicrobial stewardship efforts in the ED should
      target high-impact areas: antibiotic prescribing for nonindicated respiratory
      tract conditions, such as bronchitis and sinusitis; overtreatment of asymptomatic
      bacteriuria; and using two antibiotics (double coverage) for uncomplicated cases
      of cellulitis or abscess.

PMID- 30297011
TI  - Infectious Disease Emergencies.

PMID- 30297008
TI  - Infectious Diseases After Hydrologic Disasters.
AB  - Hydrologic disasters, including hurricanes, tsunamis, and severe flooding, have
      been associated with infectious diseases, particularly among vulnerable and
      displaced populations in resource-poor settings. Skin and soft tissue infections,
      gastrointestinal infections, respiratory infections, zoonotic infections, and
      vector-borne diseases each present unique threats to human health in this
      setting. Increased emergency physician awareness of these infectious diseases and
      their diagnosis and management helps optimize medical care for survivors after a
      hydrologic disaster and safeguard the health of disaster responders.

PMID- 30297012
TI  - Here to Stay: Infectious Diseases in Emergency Medicine.

PMID- 30297014
TI  - Celebrating the Expanded Food and Nutrition Education Program's Anniversary.

PMID- 30297013
TI  -  Is Internalization an End in Itself or a Means to an End?

PMID- 30297010
TI  - Infection Prevention for the Emergency Department: Out of Reach or Standard of
      Care?
AB  - The emergency department (ED) presents unique challenges to infection control and
      prevention. Hand hygiene, transmission-based precautions, environmental cleaning,
      high-level disinfection and sterilization of reusable medical devices, and
      prevention of health care-associated infections (catheter-associated urinary
      tract infection, ventilator-associated pneumonia, central line-associated
      bloodstream infection) are key priorities in ED infection prevention. Effective
      and sustainable infection prevention strategies tailored to the ED are necessary
      and achievable. Emergency clinicians can and already play an invaluable role in
      infection prevention.

PMID- 30297016
TI  - Digital Promotion of Energy Drinks to Young Adults Is More Strongly Linked to
      Consumption Than Other Media.
AB  - OBJECTIVE: To examine whether digital marketing strategies are more strongly
      associated with energy drink use than other marketing and whether Theory of
      Planned Behavior (TPB) constructs mediated the effects of digital marketing on
      energy drink use. DESIGN: A cross-sectional online survey using the TPB was
      administered in 2016. SETTING: Illawarra region of New South Wales, Australia.
      PARTICIPANTS: A total of 359 young adults aged 18-24 years completed the survey.
      Participants were mainly students. MAIN OUTCOME MEASURES: Relative impacts of
      digital and other marketing on energy drink use and the mediating effects of TPB
      constructs: attitudes, subjective norm, and perceived behavioral control.
      ANALYSIS: Stepwise regression analysis was employed to compare the effects on
      energy drink use from digital and other marketing. Mediation analysis was used to
      examine the mediating effects of the TPB constructs. RESULTS: Digital marketing
      was more strongly associated than other marketing with young adults' energy drink
      use. Attitudes, subjective norms, and perceived behavioral control mediated the
      effects of digital marketing on energy drink use. CONCLUSIONS AND IMPLICATIONS:
      The marketing of unhealthy food and beverages such as energy drink products on
      the Internet requires greater scrutiny. Future interventions may focus on
      strategies to attenuate young adults' attitudes toward energy drinks, denormalize
      energy drink use, and strengthening self-efficacy to reject energy drinks among
      this age group.

PMID- 30297015
TI  - Nutrition Label Use and Its Association With Dietary Quality Among Latinos: The
      Roles of Poverty and Acculturation.
AB  - OBJECTIVE: To investigate how acculturation and poverty are independently and
      jointly associated with the use of the Nutrition Facts panel (nutrition label)
      and to examine the extent to which nutrition label use moderates the association
      of poverty and acculturation on dietary quality among Latinos. DESIGN: Cross
      sectional analysis of the 2007/2008 and 2009/2010 waves of the National Health
      and Nutrition Examination Survey. PARTICIPANTS: A total of 3,696 adults (aged >19
      years) self-identified as Latino/Hispanic with food label use data from the most
      recent Consumer Behavior Phone Follow-Up Modules. MAIN OUTCOME MEASURE(S):
      Nutrition label use and dietary quality. ANALYSIS: Logistic regression. RESULTS:
      Acculturation moderated the association of income on the likelihood of using
      nutrition labels, such that lower-income English-speaking Latinos were half as
      likely as higher-income English-speakers to use nutrition labels (P = .01, odds
      ratio [OR] = 0.44, 95% confidence interval [CI], 0.24-0.81); however, Spanish
      speakers were equally likely to use nutrition labels across income levels (P =
      .99; OR = 1.00; 95% CI, 0.77-1.31). Nutrition label use moderated the association
      of acculturation on diet. Among English-speaking Latinos, those who read
      nutrition labels had less than half the risk for poor diet (P =.001; OR = 0.43;
      95% CI, 0.26-0.69); however, label use was not significantly associated with the
      diet quality of Spanish speakers (P = .07; OR = 0.82; 95% CI, 0.67-1.02).
      Nutrition label use decreased the risk for poor dietary quality regardless of
      poverty status. CONCLUSIONS AND IMPLICATIONS: Overall, results demonstrated a
      positive association between the use of the Nutrition Facts panel for Latinos and
      dietary quality. An important nutrition education strategy among bicultural
      Latinos at risk for a poor diet as a result of acculturation may include label
      reading comprehension. This approach may also address the low rates of label use.
      The study provides evidence of segmented assimilation in which low-income,
      bicultural Latinos follow an underclass pattern of acculturation demonstrated by
      a lower likelihood of reading nutrition labels and higher-income, bicultural
      Latinos follow the more successful selective pattern.

PMID- 30297017
TI  - Examining the Accuracy and Use of Portion Size Estimation Aids in Parents of
      Children With Obesity: A Randomized Controlled Trial.
AB  - OBJECTIVE: To determine parents' (1) accuracy in using portion size estimation
      aids (PSEAs) to estimate portion sizes and (2) use of PSEAs at home. METHODS:
      Parents (n = 37) of children in a pediatric weight management clinic were
      recruited, enrolled in a parallel-design, randomized, controlled trial, and
      assigned to receive a 2-dimensional (2D) or 3D PSEA. Percent absolute estimation
      accuracy was examined across groups and food types. Survey responses were
      organized according to frequencies and percentages were calculated. RESULTS: Main
      effects of group, food type, and group * food type interaction were significant
      (all P < .05). The 2D PSEAs yielded more accurate estimates of portion sizes for
      amorphous foods. Overall, parents' estimation accuracy was poor. Participants
      were satisfied and found the PSEAs to be useful. CONCLUSIONS AND IMPLICATIONS:
      The 2D PSEAs led to greater accuracy in estimating portions of amorphous foods.
      Parents showed poor accuracy in estimating portion sizes. This study highlights
      the role of dietitians and nutrition educators in enhancing portion estimation
      accuracy.

PMID- 30297019
TI  - Corrigendum.

PMID- 30297018
TI  - Dietary Intake Changes in Response to a Sugar-Sweetened Beverage Reduction Trial
      for Various Supplemental Nutrition Assistance Program (SNAP) Eligibility Groups.
AB  - OBJECTIVE: To examine dietary intake differences resulting from a sugar-sweetened
      beverage reduction intervention by 3 Supplemental Nutrition Assistance Program
      (SNAP) participation groups: SNAP participants (n = 56), income-eligible
      nonparticipants (n = 30), and income-ineligible nonparticipants (n = 60).
      METHODS: Adults in southwest Virginia were enrolled in a 6-month behavioral
      trial. The researchers collected SNAP enrollment status and 3 24-hour dietary
      recalls at baseline and 6 months. Repeated-measures ANOVAs were used to assess
      differences in dietary intake among SNAP participation groups. RESULTS: No
      significant group * time differences were found for energy density, Healthy
      Eating Index scores, Healthy Beverage Index scores, or intake of total calories,
      added sugars, and sugar-sweetened beverages. However, several within-group
      improvements were noted: income-ineligible nonparticipants and SNAP participants
      improved in more areas compared with income-eligible nonparticipants, including
      intake of total calories, added sugars, and sugar-sweetened beverages.
      CONCLUSIONS AND IMPLICATIONS: This exploratory analysis suggests that the overall
      effectiveness of a sugar-sweetened beverage intake reduction intervention was not
      influenced by SNAP eligibility and participation status, because there were no
      significant group by time differences over the intervention. It is important to
      recognize for future programs that different approaches to improving dietary
      intake may be needed to match the characteristics of this audience better. This
      may be accomplished by attempting to decrease the disparity gap between income
      eligible nonparticipants and those receiving SNAP or who are income ineligible
      through the use of programs such as SIPsmartER.

PMID- 30297020
TI  - The Power of Collaboration and Data Aggregation.

PMID- 30297021
TI  - Predicting Persisting Disability in Schizophrenia: The Potential of Neuroimaging.

PMID- 30297023
TI  - Using Neuroscience to Make Sense of Psychopathy.

PMID- 30297022
TI  - Evolving Concepts in Brain Oscillations and Cognitive Control in Schizophrenia.

PMID- 30297024
TI  - Cortical Hub Failure in Schizophrenia.

PMID- 30297025
TI  - Excitation and emission wavelength dependence of fluorescence spectra in whole
      cells of the cyanobacterium Synechocystis sp. PPC6803: Influence on the
      estimation of Photosystem II maximal quantum efficiency.
AB  - The fluorescence emission spectrum of Synechocystis sp. PPC6803 cells, at room
      temperature, displays: i) significant bandshape variations when collected under
      open (F0) and closed (FM) Photosystem II reaction centre conditions; ii) a marked
      dependence on the excitation wavelength both under F0 and FM conditions, due to
      the enhancement of phycobilisomes (PBS) emission upon their direct excitation. As
      a consequence: iii) the ratio of the variable and maximal fluorescence (FV/FM),
      that is a commonly employed indicator of the maximal photochemical quantum
      efficiency of PSII (Phipc, PSII), displays a significant dependency on both the
      excitation and the emission (detection) wavelength; iv) the FV/FM
      excitation/emission wavelength dependency is due, primarily, to the overlap of
      PSII emission with that of supercomplexes showing negligible changes in quantum
      yield upon trap closure, i.e. PSI and a PBS fraction which is incapable to
      transfer the excitation energy efficiently to core complexes. v) The contribution
      to the cellular emission and the relative absorption-cross section of PSII, PSI
      and uncoupled PBS are extracted using a spectral decomposition strategy. It is
      concluded that vi) Phipc, PSII is generally underestimated from the FV/FM
      measurements in this organism and, the degree of the estimation bias, which can
      exceed 50%, depends on the measurement conditions. Spectral modelling based on
      the decomposed emission/cross-section profiles were extended to other processes
      typically monitored from steady-state fluorescence measurements, in the presence
      of an actinic illumination, in particular non-photochemical quenching. It is
      suggested that vii) the quenching extent is generally underestimated in analogy
      to FV/FM but that viii) the location of quenching sites can be discriminated
      based on the combined excitation/emission spectral analysis.

PMID- 30297026
TI  - Molecular identification and functional characterization of a novel glutamate
      transporter in yeast and plant mitochondria.
AB  - The genome of Saccharomyces cerevisiae encodes 35 members of the mitochondrial
      carrier family (MCF) and 58 MCF members are coded by the genome of Arabidopsis
      thaliana, most of which have been functionally characterized. Here two members of
      this family, Ymc2p from S. cerevisiae and BOU from Arabidopsis, have been
      thoroughly characterized. These proteins were overproduced in bacteria and
      reconstituted into liposomes. Their transport properties and kinetic parameters
      demonstrate that Ymc2p and BOU transport glutamate, and to a much lesser extent L
      homocysteinesulfinate, but not other amino acids and many other tested
      metabolites. Transport catalyzed by both carriers was saturable, inhibited by
      mercuric chloride and dependent on the proton gradient across the proteoliposomal
      membrane. The growth phenotype of S. cerevisiae cells lacking the genes ymc2 and
      agc1, which encodes the only other S. cerevisiae carrier capable to transport
      glutamate besides aspartate, was fully complemented by expressing Ymc2p, Agc1p or
      BOU. Mitochondrial extracts derived from ymc2Deltaagc1Delta cells, reconstituted
      into liposomes, exhibited no glutamate transport at variance with wild-type,
      ymc2Delta and agc1Delta cells, showing that S. cerevisiae cells grown in the
      presence of acetate do not contain additional mitochondrial transporters for
      glutamate besides Ymc2p and Agc1p. Furthermore, mitochondria isolated from wild
      type, ymc2Delta and agc1Delta strains, but not from the double mutant
      ymc2Deltaagc1Delta strain, swell in isosmotic ammonium glutamate showing that
      glutamate is transported by Ymc2p and Agc1p together with a H+. It is proposed
      that the function of Ymc2p and BOU is to transport glutamate across the
      mitochondrial inner membrane and thereby play a role in intermediary metabolism,
      C1 metabolism and mitochondrial protein synthesis.

PMID- 30297027
TI  - Light transmission/absorption characteristics of the meibomian gland.
AB  - PURPOSE: While meibography has proven useful in identifying structural changes in
      the meibomian gland (MG), little is known regarding the MG spectral transmission
      and absorption characteristics. The purpose of this study was to measure the
      transmission/absorption spectra of the MG compared to other eyelid tissues.
      METHODS: Human and rabbit eyelids were fixed in paraformaldehyde, serial
      sectioned (50 MUm) using a cryotome and imaged by brightfield and reflectance
      microscopy. Eyelid regions (MG, muscle, tarsus and dermis) were then illuminated
      by a 100 MUm spot using a infrared enhanced white light source. Transmission
      spectra over a 550-950 nm range were then measured using a spectrometer and
      differences compared using two-way analysis of variance. RESULTS: Brightfield
      microscopy of both human and rabbit eyelid tissue showed a marked decrease in
      light transmission for MG acini compared to other eyelid tissues. In rabbit, the
      dermis showed 5* and the muscle showed 2* more light transmission compared to MG
      (P < .001 and P < .001, respectively). For human, the muscle showed 14* and the
      tarsus showed 84* more light transmission compared to MG (P < .01 and P < .001,
      respectively). No specific spectral region of light absorption could be detected
      in either rabbit or human MG. Loss of light transmission in MG was localized to
      acini containing small lipid droplets, averaging 2.7 +/- 0.8 MUm in diameter.
      CONCLUSIONS: The data suggest that light transmission is dramatically reduced in
      the acini due to light scattering by small lipid droplets, suggesting that
      Meibography detects active lipid synthesis in differentiating meibocytes.

PMID- 30297028
TI  - Subjective versus objective dry eye disease in patients with moderate-severe
      thyroid eye disease.
AB  - PURPOSE: To compare the subjective versus Objective dry eye disease (DED) in
      patients with moderate-severe thyroid eye disease (TED). METHOD: Included were
      the patients with moderate-severe TED and >=18 years old. They completed the
      ocular surface disease index (OSDI) questionnaire and had Schirmer, Tear breakup
      time (TBUT), fluorescein staining, osmolarity, corneal aesthesiometry, and
      meibomian gland dysfunction (MGD) tests. Excluded were patients with history of
      any disease, surgery and or medications which might be affecting the ocular
      surface and incomplete tests results. Subjective DED was defined as OSDI score of
      >=13 and objective as one abnormal sign (TBUT, Schirmer, Osmolarity, and
      Staining). Presence of both was defined as definite DED. RESULTS: Included were
      38 patients (74 eyes) with mean age of 40 years. Subjective DED was detected in
      77%, objective in 89.2%, and definite in 67.7% of the eyes. Severe subjective and
      objective DED were found in 36.5% and 24.3% of the eyes, respectively. TBUT was
      the most frequent positive test (63.5%). MGD was observed in 56.8% of the eyes.
      Mean clinical activity score, palpebral fissure, rundle grading, proptosis,
      corneal aesthesiometry, and presence of MGD were not significantly different
      between the eyes with and without subjective, objective, or definite DED.
      CONCLUSION: Definite DED was found in more than 2/3 of the eyes with moderate
      severe TED. While frequency of objective DED was higher, severe form of
      subjective DED was more frequent. No variable was significantly different between
      the eyes with and without subjective, objective and definite DED.

PMID- 30297029
TI  - Chronic Human Immunodeficiency Virus Infection With and Without Comorbidities
      Appears to Converge Toward Early Pathological Brain Aging.

PMID- 30297030
TI  - Exploring the Role of Social Cognition in the Relationship Between Trauma and
      Psychopathology.

PMID- 30297031
TI  - Resting State Brain Patterns, Cognitive Ability, and Meritocracy.

PMID- 30297032
TI  - Intraoperative radiotherapy with the Intrabeam(r) device for the treatment of
      resectable pancreatic adenocarcinoma.
AB  - INTRODUCTION: The application of intraoperative radiation therapy to the tumor
      bed after resection of pancreatic cancer has been shown to be beneficial in the
      local control of the disease. The objective of this study was to evaluate the
      preliminary outcomes after the application of a single intraoperative dose to the
      tumor bed with a new intraoperative radiotherapy device (Intrabeam(r)) in terms
      of viability, safety and short-term results. METHODS: We studied 5 patients who
      underwent pancreaticoduodenectomy for resectable pancreatic cancer in which a
      radiotherapy boost (5Gy) was intraoperatively applied to the tumoral bed using
      the portable Intrabeam(r) device, a low-energy point-source X-ray. Postoperative
      complications, hospital stay and mortality, recurrences and short-term survival
      were analyzed. RESULTS: Mean patient age was 68 years. All patients had a T3
      stage tumor and one of them N1. In 3 patients, R0 resection was performed, while
      R1 resection was conducted in 2. Perioperative mortality was 0%. The only
      complications included delayed gastric emptying and postoperative hemorrhage.
      There were no pancreatic fistulas. During follow-up (mean: 11.2 months), there
      was a relapse in the patient who had undergone R1 resection. CONCLUSIONS: The
      application of radiotherapy with the Intrabeam(r) device in selected patients has
      not resulted in increased perioperative morbidity or mortality; therefore, this
      is a safe procedure for the treatment of resectable cancer.

PMID- 30297033
TI  - Abdominal eventration with massive visceral content.

PMID- 30297035
TI  - The added value of contrast-enhanced ultrasound to conventional ultrasound in
      differentiating benign and malignant solid breast lesions: a systematic review
      and meta-analysis.
AB  - AIM: To investigate the added value of contrast-enhanced ultrasound (CEUS) to the
      conventional ultrasound (US) in the diagnosis of breast lesions. MATERIALS AND
      METHODS: PubMed, EMBASE, and Web of Science were searched for relevant studies
      published between 24 May 2005, and 29 October 2017. Studies incorporating CEUS
      into the conventional US were included. The reference standard was set by means
      of histopathological findings. The quality assessment of diagnostic studies
      (QUADAS) instrument was used to assess the quality of the included studies. Meta
      Disc version 1.4. was used to calculate the sensitivity, specificity, summary
      receiver-operating characteristic (sROC) curves, and area under the curve (AUC).
      Meta-regression with Stata 12.0 was used to compare the diagnostic accuracy of
      the two techniques. RESULTS: Five studies, comprising 992 patients, were eligible
      for this meta-analysis. For conventional US, the pooled sensitivity and
      specificity for were 0.87 (95% confidence interval [CI]: 0.84-0.91) and 0.80 (95%
      CI: 0.76-0.84), respectively, the AUC was 0.9049. For CEUS-rerated US, the pooled
      sensitivity and specificity were 0.93 (95% CI: 0.90-0.95) and 0.87 (95% CI: 0.84
      0.90). The AUC was 0.9482. Meta-regression showed the sensitivity of CEUS-rerated
      US did not differ from conventional US (p=0.29), while specificity showed
      significant difference (p<0.01). There was evidence of between-study
      heterogeneity regarding sensitivity and specificity for both assessments.
      CONCLUSIONS: Adding CEUS to conventional US could improve the diagnostic
      performance in differentiating benign from malignant solid breast lesions, whilst
      retaining high sensitivity, especially in Breast Imaging-Reporting and Data
      System (BI-RADS) 3-5 lesions. A uniform standard to distinguish benign from
      malignant lesions might be needed for further clinical application.

PMID- 30297034
TI  - Quality of recovery after surgery for cancer treatment.
AB  - INTRODUCTION: Assessment of quality of recovery is important as an end-point for
      outcome research. This study aims to determine the incidence and determinants of
      poor quality of recovery (PQR) after surgery in patients scheduled for curative
      neoplastic surgery. MATERIALS AND METHODS: An observational prospective study was
      performed in consecutive patients undergoing surgery for cancer treatment. The
      Quality of Recovery 15 score (QoR-15) was applied on the day before surgery (T0)
      and 24h after (T1). PQR was defined for patients with a QoR-15 score lower than
      the mean QoR-15 score at T1 minus one standard deviation. Preoperative quality of
      life was assessed with EuroQol-5D. Frailty and disability were defined using
      Clinical Frailty Scale and World Health Organization Disability Assessment
      Schedule 2.0. RESULTS: One hundred and thirty-eight patients were enrolled and 31
      (15.9%) were identified as having PQR. At T0, patients with PQR presented lower
      scores on total QoR-15 (P=.03) and had more problems on EuroQol-5D in mobility
      (P=.014), self-care (P=.027) and usual activities domains (P=.019). The
      difference of QoR-15 score between T1 and T0 was higher in PQR patients (P<.001).
      PQR had more frequently Revised Cardiac Risk Index (RCRI)>=2 (P=.012) and were
      more frequently frail (P=.03). PQR patients stayed longer in the hospital
      (P=.034). CONCLUSION: PQR patients had lower QoR-15 before surgery, poor quality
      of life, were more frequently frail and had high cardiac risk factors. PQR
      patients stayed longer in the hospital.

PMID- 30297036
TI  - Design analysis indicates Potential overestimation of treatment effects in
      randomized controlled trials supporting Food and Drug Administration cancer drug
      approvals.
AB  - OBJECTIVE: Statistical significance drives interpretation of randomized
      controlled trials (RCTs). We examined the type S error risk-claiming a new drug
      is falsely beneficial-and exaggeration ratio-how estimated effects differ from
      true effects-to re-emphasize direction and magnitude of treatment effects. STUDY
      DESIGN AND SETTING: We systematically reviewed RCTs supporting Food and Drug
      Administration (FDA) approval of cancer drugs between 2007 and 2016. We extracted
      data for overall survival (OS), progression-free survival (PFS), and response
      outcomes from FDA reviews. We estimated type S error risks and exaggeration
      ratios by considering replicated RCTs of equal size and a range of true effects.
      RESULTS: We analyzed 42 RCTs for 39 approved drugs. Across 38 RCTs reporting OS,
      the median type S error risk was 0.00% (Q1-Q3, 0.00-0.01%) and 3.56% (0.40
      6.74%), for true hazard ratios of 0.7 and 0.9, respectively, indicating
      confidence in effect direction. The corresponding exaggeration ratios were 1.09
      (1.01-1.11) and 1.30 (1.13-1.42), indicating median overestimations of 9% and
      30%. Similar results held for PFS and response outcomes. CONCLUSIONS: The type S
      error risk and exaggeration ratio provide additional insights into the
      replicability of RCTs. Our analyses also quantify the winner's curse, in which
      pivotal RCTs tend toward overoptimism.

PMID- 30297037
TI  - Improving the conduct of systematic reviews: a process mining perspective.
AB  - OBJECTIVES: To illustrate the use of process mining concepts, techniques, and
      tools to improve the systematic review process. STUDY DESIGN AND SETTING: We
      simulated review activities and step-specific methods in the process for
      systematic reviews conducted by one research team over 1 year to generate an
      event log of activities, with start/end dates, reviewer assignment by expertise,
      and person-hours worked. Process mining techniques were applied to the event log
      to "discover" process models, which allowed visual display, animation, or replay
      of the simulated review activities. Summary statistics were calculated for person
      time and timelines. We also analyzed the social networks of team interactions.
      RESULTS: The 12 simulated reviews included an average of 3,831 titles/abstracts
      (range: 1,565-6,368) and 20 studies (6-42). The average review completion time
      was 463 days (range: 289-629) (881 person-hours [range: 243-1,752]). The average
      person-hours per activity were study selection 26%, data collection 24%, report
      preparation 23%, and meta-analysis 17%. Social network analyses showed the
      organizational interaction of team members, including how they worked together to
      complete review tasks and to hand over tasks upon completion. CONCLUSION: Event
      log and process mining can be valuable tools for research teams interested in
      improving and modernizing the systematic review process.

PMID- 30297038
TI  - Advanced imaging modalities to detect cardiotoxicity.
AB  - Recent advances in cancer treatments have significantly improved survival rates,
      reemphasizing the focus on reducing the potential complications associated with
      some therapies. Cardiovascular disease associated with chemotherapies is a major
      cause of morbidity and mortality in cancer survivors. Early detection of
      cardiotoxicity improves cardiac outcomes among cancer patients. The review will
      focus on imaging modalities used to assess cardiotoxicity - the cardiovascular
      consequences of chemotherapies. The review will discuss the benefits and
      limitations associated with each technique, as well as the guidelines available
      to help identify at risk patients. We will discuss novel techniques that may help
      detect earlier signs of cardiotoxicity, directing management that may improve
      clinical outcomes.

PMID- 30297039
TI  - Does only the age of the hen matter in Salmonella enterica contamination of eggs?
AB  - Contamination of eggs with Salmonella enterica is a significant risk factor
      contributing to foodborne disease. Periods of peak egg contamination were
      identified by conducting longitudinal environmental and egg sampling in 7 layer
      flocks until they were 50 weeks of age. A total of 714 environmental samples and
      8958 eggs were cultured using standard methods for the detection of salmonellae.
      Pooled egg contamination with Salmonella Typhimurium or Salmonella Infantis was
      detected at a true prevalence (TP) of 0.002 (95% CI = 0.001, 0.004) or 0.005 (95%
      CI = 0.004, 0.007), respectively. S. Typhimurium and S. Infantis were detected in
      individual egg components; in shell rinse at a TP of 0.014 (95% CI = 0.005,
      0.038), in shell and membrane at a TP of 0.01 (95% CI = 0.003, 0.032), and in
      albumen and yolk content at a TP of 0.007 (95% CI = 0.001, 0.027). The
      concentration of salmonellae in all fractions was <1 CFU/mL. The TP of Salmonella
      enterica in eggs was highest at the onset of lay. Higher egg prevalence was
      associated with a lower body weight, higher egg production, higher egg weight and
      mass than the breed standard for age, and poorer feed conversion efficiency.
      Flock physiology appears to have an important influence on the detection of eggs
      contaminated with Salmonella enterica.

PMID- 30297040
TI  - Assessment of the non-lactic acid bacteria microbiota in fresh cucumbers and
      commercially fermented cucumber pickles brined with 6% NaCl.
AB  - Limited documentation of the cucumber fermentation microbiome has impeded the
      understanding of the role of microbes on the quality of finished products. We
      characterized the microbiome of fresh and fermented cucumber samples using
      culture dependent and independent techniques, with an emphasis on the non-lactic
      acid bacteria (non-LAB) population. Insubstantial microbiome variations were
      observed among fresh cucumber types with Rhizobium (31.04%), Pseudomonas
      (14.08%), Pantoea (9.25%), Stenotrophomonas (6.83%), and Acinetobacter (6.5%)
      prevailing. The relative abundance of LAB remained below 0.4% and 4.0% on fresh
      cucumbers and day 3 of the fermentations brined with 6% sodium chloride,
      respectively. Fermentation cover brine samples collected on day 1 harbored
      Pseudomonas, Pantoea, Stenotrophomonas, Acinetobacter, Comamonas, Wautersiella,
      Microbacterium, Flavobacterium, Ochrobactrum and the Enterobacteriaceae,
      Citrobacter, Enterobacter and Kluyvera. Plate counts for presumptive Klebsiella
      and Pseudomonas from fermentation cover brine samples reached 2.80 +/- 0.36 and
      2.78 +/- 0.83 log of CFU/mL, respectively, in 30% and 60% of the nine tanks
      scrutinized with selective media. Both genera were found in cover brine samples
      with pH values at 4.04 +/- 0.15. We aim at elucidating whether the low relative
      abundance of non-LAB in commercial cucumber fermentations, in particular
      Pseudomonas and Enterobacteriaceae, impacts the quality of fermented cucumbers.

PMID- 30297041
TI  - Microbial characterisation of the edible grasshopper Ruspolia differens in raw
      condition after wild-harvesting in Uganda.
AB  - This research aimed at establishing the chemical intrinsic properties and the
      microbial quality of an edible grasshopper Ruspolia differens and the effect of
      its source (geographical area) in Uganda, trading point, swarming season and
      plucking on these parameters. The intrinsic properties of the grasshopper can
      support the growth of a wide variety of microorganisms. High counts of total
      aerobic microbes, Enterobacteriaceae, lactic acid bacteria, total aerobic spores,
      and yeasts and moulds were obtained. Metagenetic analyses yielded 1793
      Operational Taxonomic Units (OTUs) belonging to 24 phyla. Actinobacteria,
      Bacteroidetes, Firmicutes, Fusobacteria and Proteobacteria were the most abundant
      phyla, while members of the genera Acinetobacter, Buttiauxella, Lactococcus,
      Staphylococcus and Undibacterium were the most abundant OTUs. A number of genera
      harbouring potential pathogens (Acinetobacter, Bacillus, Buttiauxella,
      Campylobacter, Clostridium, Staphylococcus, Pseudomonas and Neisseria) were
      identified. The geographical area, trading point, swarming season and plucking
      significantly influenced microbial counts and bacterial diversity. The high
      microbial counts predispose R. differens to fast microbial spoilage, while the
      presence of Clostridium and Campylobacter makes this grasshopper a potential
      source of food borne diseases. Further research should identify the specific
      spoilage microorganisms of R. differens and assess the characteristics of this
      grasshopper that support growth of food pathogens.

PMID- 30297042
TI  - A review of Clostridioides [Clostridium] difficile occurrence through the food
      chain.
AB  - The epidemiology and transmission of Clostridioides difficile, particularly for
      community-associated infections, are not completely understood. Although there
      have been no confirmed cases of any foodborne disease caused by C. difficile, its
      occurrence in livestock and foods suggests that contaminated food products with
      spores could be a vehicle to spread C. difficile infection. This review proposes
      potential sources of C. difficile infection in the community and contamination
      routes of food products. Based on European research, it also summarizes the
      occurrence and organism characterization of C. difficile in animals at
      slaughterhouses and in human foods. Most of the analyzed literature reported
      prevalence in retail foods of less than 8%, including microorganism belonging to
      the ribotype 078, an important hypervirulent strain involved in disease in
      humans. This prevalence in Europe is underestimated, being lower that reported in
      North America (rates up to 42%), probably due of the lack of an ISO procedure for
      the detection of C. difficile in food products that preclude the comparison of
      prevalence data from different studies. The survival and growth of vegetative C.
      difficile cells and the resistance of its spores in foods are discussed as well
      as the risk factors of acquisition CDI from food products.

PMID- 30297043
TI  - Sequential treatment of hydrogen peroxide, vacuum packaging, and dry heat for
      inactivating Salmonella Typhimurium on alfalfa seeds without detrimental effect
      on seeds viability.
AB  - The aim of this study was to inactivate Salmonella Typhimurium loaded onto
      alfalfa seeds with sequential treatment of hydrogen peroxide, drying, vacuum
      packaging, and dry heat. Also, we verified the effect of vacuum packaging in dry
      heat treatment. Populations of Salmonella on alfalfa seeds after sequential
      treatment were not detected after 8 or 3 h of dry heat treatment at 70 or 73 
      degrees C. Salmonella populations including injured cells were also reduced to
      below the detection limit after 8 or 4 h of dry heat treatment. The germination
      rate of alfalfa seeds subjected to the harshest treatment was not significantly
      different (P > 0.05) from that of untreated seeds. Vacuum packaging is conducive
      to preserving the moisture content of alfalfa seed and improving the efficiency
      of dry heat treatment. This study suggests that sequential treatment is
      recommended and applicable for decontaminating alfalfa seeds for sprout
      production.

PMID- 30297044
TI  - Evaluation of sampling methods for the detection of pathogenic bacteria on pre
      harvest leafy greens.
AB  - Recent outbreaks of foodborne disease associated with leafy greens have led to
      increased pre-harvest testing for pathogens and indicator microorganisms.
      However, the scientific and statistical rationale and the performance attributes
      for pre-harvest sampling methods are not well understood. The performance of
      three pre-harvest sampling methods, random, stratified random, and Z-pattern
      sampling, was evaluated by consideration of their mathematical derivations,
      computer simulations and field validation. Consideration of the probabilistic
      basis of the sampling methods indicated that the mean detection rates were
      similar. However, use of simulation modeling to assess the uncertainty associated
      with the three sampling methods indicated that the inherent variability of the Z
      pattern sampling method was substantially greater than the other two sampling
      methods. A simulation tool was developed in Matlab that allowed the evaluation of
      the effectiveness of the three sampling methods. A limited validation study also
      observed that Z-pattern sampling had higher variability than the other two
      sampling methods. This study indicates that while the mean detection
      probabilities for the three sampling methods are similar, the random or
      stratified random sampling are less variable, particularly when the number of
      contamination sites or number of samples analyzed are small.

PMID- 30297045
TI  - Genomic and metabolic features of the Bacillus amyloliquefaciens group- B.
      amyloliquefaciens, B. velezensis, and B. siamensis- revealed by pan-genome
      analysis.
AB  - The genomic and metabolic features of the Bacillus amyloliquefaciens group
      comprising B. amyloliquefaciens, B. velezensis, and B. siamensis were
      investigated through a pan-genome analysis combined with an experimental
      verification of some of the functions identified. All B. amyloliquefaciens group
      genomes were retrieved from GenBank and their phylogenetic relatedness was
      subsequently investigated. Genome comparisons of B. amyloliquefaciens, B.
      siamensis, and B. velezensis showed that their genomic and metabolic features
      were similar; however species-specific features were also identified. Energy
      metabolism-related genes are more enriched in B. amyloliquefaciens, whereas
      secondary metabolite biosynthesis-related genes are enriched in B. velezensis.
      Compared to B. amyloliquefaciens and B. siamensis, B. velezensis harbors more
      genes in its core-genome which are involved in the biosynthesis of antimicrobial
      compounds, as well as genes involved in d-galacturonate and d-fructuronate
      metabolism. B. amyloliquefaciens, B. siamensis, and B. velezensis all harbor a
      xanthine oxidase gene cluster (xoABCDE) in their core-genomes that is involved in
      metabolizing xanthine and uric acid to glycine and oxalureate. A reconstruction
      of B. amyloliquefaciens group metabolic pathways using their individual pan
      genomes revealed that the B. amyloliquefaciens group strains have the ability to
      metabolize diverse carbon sources aerobically, or anaerobically, and can produce
      various metabolites such as lactate, ethanol, acetate, CO2, xylitol, diacetyl,
      acetoin, and 2,3-butanediol. This study therefore provides insights into the
      genomic and metabolic features of the B. amyloliquefaciens group.

PMID- 30297046
TI  - Growth and metabolism of non-Saccharomyces yeasts isolated from Washington state
      vineyards in media and high sugar grape musts.
AB  - Utilization of carbohydrates and amino acids/ammonium by selected non
      Saccharomyces yeasts and impacts on alcoholic fermentation was evaluated using
      media and high sugar grape musts (>270 g/L). Consumption patterns of single
      cultures were ascertained in synthetic media and a Chardonnay grape must. While
      the non-Saccharomyces species maintained >106 cfu/mL after >40 days,
      concentrations of residual sugars ranged from 103 g/L (Wickerhamomyces anomalus)
      to 155 g/L (Candida californica), amino acids and ammonium were generally
      depleted (>85%), and excessive amounts of volatile acidity (>0.8 g/L) were
      sometimes produced (e.g., C. oleophila). To minimize problems associated with
      nutrient depletion before alcoholic fermentation, non-Saccharomyces yeasts were
      inoculated six days ahead of S. cerevisiae into Syrah grape musts. Syrah ferments
      inoculated with C. californica or Metschnikowia pulcherrima contained lower
      concentrations of residual sugar and ethanol compared to those with only S.
      cerevisiae. Furthermore, the presence of non-Saccharomyces yeasts influenced
      concentrations of glycerol and volatile aroma compounds. These results suggested
      potential use of some non-Saccharomyces yeasts towards reducing alcohol
      concentrations without risking slower alcoholic fermentations.

PMID- 30297047
TI  - Comparative evaluation of spoilage-related bacterial diversity and metabolite
      profiles in chilled beef stored under air and vacuum packaging.
AB  - Microbial spoilage is a complex event to which different bacterial populations
      and metabolites can contribute depending on the storage conditions. This study
      explored the evolution of spoilage and related volatile organic compounds (VOCs)
      in chilled beef under air and vacuum packaging (VP). The results suggested that
      different storage conditions affected changes in bacterial communities and
      metabolites in beef and consequently affected the odor properties of the stored
      beef, thereby leading to spoilage. Bacterial species belonging to
      Pseudomonadaceae (Pseudomonas spp.) and lactic acid bacteria (Lactobacillus sp.)
      dominated the bacterial communities in beef stored under air and VP,
      respectively, with several VOCs associated with off-odors of the stored beef and
      most likely produced by both bacteria. Our results suggested several microbial
      VOCs that could be used as potential spoilage indicators, including acetic acid,
      butanoic acid, and 2-butanone in VP-stored beef and 3-methylbutan-1-ol, ethyl
      acetate, acetoin, 2-butanone, and diacetyl in air-stored beef. These findings
      might provide valuable information regarding the quality monitoring of beef
      during storage.

PMID- 30297048
TI  - Evaluation of post-contamination survival and persistence of applied attenuated
      E. coli O157:H7 and naturally-contaminating E. coli O157:H7 on spinach under
      field conditions and following postharvest handling.
AB  - This study determined the variability in population uniformity of an applied
      mixture of attenuated E. coli O157:H7 (attEcO157) on spinach leaves as impacted
      by sampling mass and detection technique over spatial and temporal conditions.
      Opportunistically, the survival and distribution of naturally contaminating
      pathogenic E. coli O157:H7 (EcO157), in a single packaged lot following
      commercial postharvest handling and washing, was also evaluated. From the main
      study outcomes, differences in the applied inoculum dose of 100-fold, resulted in
      indistinguishable population densities of approximately Log 1.1 CFU g-1 by 14
      days post-inoculation (DPI). Composite leaf samples of 150 g and the inclusion of
      the spinach petiole resulted in the greatest numerical sensitivity of detection
      of attEcO157 when compared to 25 and 150 g samples without petioles (P < 0.05).
      Differences in population density and protected-site survival and potential leaf
      internalization were observed between growing seasons and locations in California
      (P < 0.05). A Double Weibull model best described and identified two distinct
      populations with different inactivation rates of the inoculated attEcO157. Linear
      die-off rates varied between 0.14 and 0.29 Log/Day irrespective of location.
      Detection of EcO157- stx1-negative and stx2-positive, resulting from a natural
      contamination event, was observed in 11 of 26 quarantined commercial units of
      washed spinach by applying the 150 g sample mass protocol. The capacity to detect
      EcO157 varied between commercial test kits and non-commercial qPCR. Our findings
      suggest the need for modifications to routine pathogen sampling protocols
      employed for lot acceptance of spinach and other leafy greens.

PMID- 30297049
TI  - Contamination of chicken meat with extended-spectrum beta-lactamase producing-
      Klebsiella pneumoniae and Escherichia coli during scalding and defeathering of
      broiler carcasses.
AB  - Extended-spectrum beta-lactamase- (ESBL-) producing Klebsiella (K.) pneumoniae
      and Escherichia (E.) coli are of critical importance in human and veterinary
      medicine. Animal food products, especially broiler chickens, are discussed as a
      possible source for the exposure of humans with antibiotic resistant bacteria.
      Although the occurrence and vertical transmission of ESBL-/AmpC-producing
      Enterobacteriaceae in the broiler production has been reported before, detailed
      investigations concerning the dissemination along the slaughter processing line
      are missing. In this study, we investigated cross-contamination with ESBL
      producing Enterobacteriaceae during the processing of two different broiler
      flocks in one slaughterhouse. The ESBL-status during the fattening period of the
      flocks was determined and environmental samples from the slaughterhouse were
      taken before processing of the respective flocks. These isolates were compared to
      those found in samples from the carcasses after processing using whole genome
      sequencing. Phylogenetic analyses of seven ESBL-producing K. pneumoniae and 14 E.
      coli revealed close relationships between isolates from scalding water and the
      defeathering machine, respectively, which were collected before the processing of
      the broiler flocks, to those isolates found in samples from skin and filet of the
      respective flock carcasses. In conclusion, using high resolution molecular data
      we found evidence for the cross-contamination of carcasses with ESBL-producing
      Enterobacteriaceae during scalding and defeathering in the slaughterhouse.

PMID- 30297050
TI  - Global transcriptomic response of Listeria monocytogenes during growth on
      cantaloupe slices.
AB  - Understanding a pathogen's response to food environments is imperative to develop
      effective control strategies as well as to elucidate the impact of foods on
      virulence potential. The purpose of this study was to assess transcriptional
      response of Listeria monocytogenes after growth in cantaloupe, as well as its
      impact on survival in synthetic gastric fluid (SGF). The transcriptional profiles
      of L. monocytogenes grown in cantaloupe or Brain Heart Infusion (BHI) under
      refrigeration were compared by a custom-designed microarray. A total of 286 and
      175 genes were significantly up- and down-regulated, respectively, in L.
      monocytogenes grown in cantaloupe as compared to BHI (fold change >= 2.5 and adj.
      P < 0.05). The majority of upregulated genes belonged to functions related to
      amino acid and nucleotide metabolism, flagellar biosynthesis, and iron
      acquisition, while most downregulated genes belonged to carbohydrate metabolism.
      Notably, the branched chain amino acid (BCAA: leucine, isoleucine, valine)
      biosynthesis operon was shown to be highly upregulated as well as the purine and
      pyrimidine biosynthesis pathways. Transcript levels of several stress- and
      virulence-related genes were significantly altered, implying an impact of growth
      in cantaloupe on the virulence potential of L. monocytogenes. Enhanced survival
      of L. monocytogenes in SGF following growth in cantaloupe further demonstrated
      the impact of cantaloupe-associated growth on the pathogen's subsequent response
      to a host relevant stress.

PMID- 30297051
TI  - Survival of clinical and food Acinetobacter spp. isolates exposed to different
      stress conditions.
AB  - Acinetobacter baumanni is recognized as one of the most important agents of
      nosocomial infections. Other species such as Acinetobacter lwoffii have also been
      associated with such infections. These species can be found in food products,
      such as vegetables, fruits and meats which can be a source of transmission of
      these organisms to community and hospital settings. Evidence that hospitals'
      kitchens are a route of entry of pathogenic and antimicrobial-resistant bacteria
      was recently demonstrated. This study aimed to determine whether different
      Acinetobacter spp. isolated from human and food samples (lettuce, turkey meat,
      apple and pear) were resistant to stress conditions often applied in food
      processes, such as exposure to 60  degrees C, AMUKINA(r) and vinegar. Also the
      influence of food matrices on the behavior of isolates to these stress conditions
      was evaluated. Treatment with AMUKINA(r) and vinegar were effective against all
      clinical and food isolates. Exposure to 60  degrees C resulted in the reduction
      of the majority of isolates to values below the detection limit of the
      enumeration technique, however, it is important to note that most of the
      reductions only occurred after 30 min of exposure. One food isolate identified as
      A. baumanni was resistant to this thermal treatment and one clinical isolate only
      decreased 4 log cycles after 1 h. In general, food isolates were demonstrated to
      be more resistant than clinical isolates and no significant differences (p >
      0.05) were found between A. baumanni and A. lwoffii species. With the exception
      of one food isolate that was more resistant to thermal stress in the presence of
      turkey meat, the food matrices investigated did not confer protection to the
      applied stresses. Due to the limited knowledge on this topic, we believe that
      this study is an important contribution to understanding the behavior of
      Acinetobacter spp. when exposed to treatments commonly applied to foods.

PMID- 30297052
TI  - Modelling the effect of oxygen concentration on bacterial growth rates.
AB  - Predicting the microbial safety of food products stored in modified atmosphere
      packaging implies taking into account the effect of oxygen reduction on microbial
      growth. According to their respiratory-type, the micro-organisms are not impacted
      similarly by the oxygen concentration. The aim of this article was to quantify
      and model the oxygen effect on the growth rates of 5 bacterial species: Listeria
      monocytogenes and Bacillus weihenstephanensis (facultative anaerobic),
      Pseudomonas fluorescens (strict aerobic), Clostridium perfringens and Clostridium
      sporogenes (strict anaerobic). The results showed the oxygen concentration
      doesn't modify the behavior of both facultative anaerobic strains. The growth
      rate of P. fluorescens decreased with the oxygen concentration, but the effect is
      only noticeable when the oxygen concentration fell below 3% in the gaseous phase.
      Conversely, the oxygen acted as a growth inhibitor for both Clostridium species.
      But total inhibition is reached only for 3.26% and 6.61% respectively for C.
      sporogenes and C. perfringens. Two models have been fitted for both respiratory
      types, the first is the Monod model considering oxygen as a substrate for growth,
      and the second is the classic inhibitory model based on minimal inhibitory
      concentration.

PMID- 30297053
TI  - Changes in the microbial communities in vacuum-packaged smoked bacon during
      storage.
AB  - This study aimed to gain deeper insights into the microbiota composition and
      population dynamics, monitor the dominant bacterial populations and identify the
      specific spoilage microorganisms (SSOs) of vacuum-packed bacon during
      refrigerated storage using both culture-independent and dependent methods. High
      throughout sequencing (HTS) showed that the microbial composition changed greatly
      with the prolongation of storage time. The diversity of microbiota was abundant
      at the initial stage then experienced a continuous decrease. Lactic acid bacteria
      (LAB) mainly Leuconostoc and Lactobacillus dominated the microbial population
      after seven days of storage. A total of 26 isolates were identified from
      different growth media using traditional cultivation isolation and identification
      method. Leuconostoc mesenteroides and Leuconostoc carnosum were the most
      prevalent species since day 15, while Lactobacillus sakei and Lactobacillus
      curvatus were only found on day 45, suggesting that they could be responsible for
      the spoilage of bacon. Serratia, Rahnella, Fusobacterium and Lactococcus
      underwent a dramatic increase at some point in individual batchs which may be
      considered as potential contributors to the spoilage.

PMID- 30297054
TI  - Spoilage indicator bacteria in farmed Atlantic salmon (Salmo salar) stored on ice
      for 10 days.
AB  - This study investigated the growth of indicator and spoilage bacteria on whole
      Atlantic salmon (Salmo salar) stored aerobically at 2  degrees C. On days 0, 2,
      3, 6, 8 and 10 microbiological analysis was carried out on inner flesh and outer
      skin samples as well as outer skin swabs (25 cm2 surface areas). Mesophilic total
      viable counts (TVCm) on skin, flesh and swab samples increased from 1.9, 1.1 and
      2.7 log10 CFUcm2 to 6.0, 5.1 and 5.7 log10 CFU/cm2 after 10 days, respectively.
      Psychrotrophic counts (TVCp), increased from 2.2, 1.8 and 3.1 log10 CFU/cm2 to
      6.2, 5.3 and 5.9 log10 CFU/cm2, for skin, flesh and swab samples respectively.
      Hydrogen sulphide producing bacteria (HSPB), lactic acid bacteria (LAB),
      Pseudomonas spp., Brochothrix thermosphacta and Photobacterium spp. grew well
      with similar growth rates (mean generation times of 17.2-26 h). It was concluded
      that the shelf-life of salmon at 2  degrees C was approximately 10 days and that
      HSPB, LAB, Pseudomonas spp., Br. thermosphacta and Photobacterium spp. may be a
      better indicator of fish spoilage rather than TVC growth, with a count of 5-6
      log10 CFU/cm2 indicating the end of shelf-life.

PMID- 30297055
TI  - Metabolism of phenolic acids in whole wheat and rye malt sourdoughs.
AB  - This work aimed to study the phenolic acid metabolism of sourdough lactic acid
      bacteria (LAB) in laboratory media, and in sourdough fermentation with single
      cultures and in co-fermentations. Lactobacilli were selected from isolates
      obtained from 35 sourdough samples. Isolates (114 strains) were screened for
      phenolic acid decarboxylase gene pdc and EPS production. Ferulic acid metabolism
      of the 18 pdc positive strains was evaluated in mMRS; all pcd positive strains
      converted ferulic acid by decarboxylation and/or reduction. Single whole wheat
      and rye malt dough fermentation fermented with lactobacilli or yeasts were
      characterized with respect to free, conjugated, or bound phenolic acids.
      Concentrations of free, conjugated, or bound phenolic acids were not altered
      substantially in chemically acidified sourdoughs, or in yeast fermented doughs.
      L. plantarum metabolized free ferulic acid in wheat and rye malt sourdoughs; L.
      hammesii DSM 16381 metabolized syringic and vanillic acids and reduced levels of
      bound ferulic acid in wheat sourdoughs. Co-fermentation of L. hammesii and L.
      plantarum achieved release of bound ferulic acid and conversion of the resultant
      free ferulic acid to dihydroferulic acid and volatile metabolites. Phenolic acid
      metabolism in sourdoughs was enhanced by co-fermentation with strains exhibiting
      complementary metabolic activities. Results may enable improvement of bread
      quality by targeted conversion of phenolic acids during sourdough fermentation.

PMID- 30297056
TI  - Effective inhibition of Salmonella Typhimurium in fresh produce by a phage
      cocktail targeting multiple host receptors.
AB  - Salmonella contamination of fresh produce is the primary bacterial cause of a
      significant number of foodborne outbreaks and infections. Bacteriophages can be
      used as natural antibacterial agents to control foodborne pathogens. However, the
      rapid development of bacterial resistance to phage infection is a significant
      barrier to practical phage application. To overcome this problem, we developed a
      novel phage cocktail consisting of the three phages (BSPM4, BSP101 and BSP22A)
      that target different host receptors, including flagella, O-antigen and BtuB,
      respectively. Whole genome sequence analysis of the phages revealed that three
      phages do not harbor genes involved in lysogen formation or toxin production,
      suggesting they are safe for use as biocontrol agents in foods. In vitro
      treatment of the phage cocktail resulted in a significant reduction in the
      development of bacterial resistance. Phage cocktail treatments achieved 4.7-5.5
      log CFU/cm2 reduction of viable cell number in iceberg lettuce and 4.8-5.8 log
      CFU/cm2 reduction in cucumber after 12 h at room temperature (25  degrees C). The
      phage cocktail exhibited good antimicrobial efficiency, suggesting that it could
      reduce S. Typhimurium contamination of fresh produce. The strategy of developing
      cocktails of phages that target multiple host receptors can be used to develop
      novel biocontrol agents of S. Typhimurium.

PMID- 30297057
TI  - In situ riboflavin fortification of different kefir-like cereal-based beverages
      using selected Andean LAB strains.
AB  - Cereal-based functional beverages represent social, economic, and environmental
      sustainable opportunities to cope with emerging trends in food consumption and
      global nutrition. Here we report, for the first time, the polyphasic
      characterization of three cereal-based kefir-like riboflavin-enriched beverages,
      obtained from oat, maize and barley flours, and their comparison with classical
      milk-based kefir. The four matrices were successfully fermented with commercial
      starters: i) milk-kefir and ii) water-kefir, proving the potential of cereal
      ingredients in the formulation of dairy-like fermented beverages with milk-kefir
      starter behavior better in these matrices. In the light of their potentiality,
      seven riboflavin-producing Andean Lactic Acid Bacteria (LAB) were tested for
      tolerance to food stresses commonly encountered during food fermentation.
      Moreover, the LAB strains investigated were screened for spontaneous riboflavin
      overproducing derivatives. Lactobacillus plantarum M5MA1-B2 with outstanding
      response to stress, was selected to improve riboflavin content in an in situ
      fortification approach. The combination of L. plantarum M5MA1-B2 riboflavin
      overproducing strain with milk kefir starter in oat, lead to cover, for one
      serving of 100 g, 11.4% of Recommended Dietary Allowance (RDA). Besides, addition
      of L. plantarum M5MA1-B2 improved performance of water kefir in oat and maize
      matrices. Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS)
      analysis provided the on-line Volatile Organic Compounds profiles supporting the
      best combination of starter, LAB and cereal matrix for novel functional foods
      development.

PMID- 30297058
TI  - Effects of Enterococcus faecalis UGRA10 and the enterocin AS-48 against the fish
      pathogen Lactococcus garvieae. Studies in vitro and in vivo.
AB  - The aim of this study was to evaluate the effects of Enterococcus faecalis UGRA10
      and its enterocin AS-48 against the fish pathogen Lactococcus garvieae. The
      minimum bactericidal concentrations of AS-48 against L. garvieae CECT 5807, 5806,
      and 5274 were 15.62, 15.62, and 7.81 MUg/ml respectively. In broth cultures,
      enterocin at 100, 50, and 25 MUg/ml reduced 108 CFU/ml lactococci after 2, 5, and
      10 h, respectively. In co-cultures of UGRA10/L. garvieae at a 1/10 CFU/ml ratio,
      lactococci were eliminated after 24 h. Studies on UGRA10 biosafety and AS-48
      toxicity in R1 cells and in rainbow trout have shown a lack of adverse effects
      from both the strain and bacteriocin. Trout challenged with L. garvieae and
      UGRA10 administered in diet 30 days before infection had a cumulative survival
      rate of 50% compared with 0% for control fish. Trout inoculated with the pathogen
      and treated by regular dipping in AS-48 baths had a survival rate of 60% after 20
      days compared with that of untreated fish (0%). These results indicate the
      protective effect of the UGRA10 strain and the bacteriocin AS-48 against L.
      garvieae and the potential of these natural products as alternatives to
      antibiotics for controlling diseases in aquaculture.

PMID- 30297059
TI  - Survival of Listeria monocytogenes during in vitro gastrointestinal digestion
      after exposure to 5 and 0.5 % sodium chloride.
AB  - The food industry is under pressure to reduce the NaCl content in food, but the
      consequences on the ability of L. monocytogenes to survive in the human host and
      cause listeriosis is not known. In this study, a recently developed
      internationally harmonized static in vitro digestion (IVD) model was used to
      investigate the survival of L. monocytogenes in the gastric and intestinal phases
      after exposure to 5 or 0.5% NaCl. Six isolates from three Scandinavian foodborne
      listeriosis outbreaks, all related to NaCl containing foods, the EGDe reference
      strain and an EGDe mutant, deleted for the major stress regulator gene, sigB,
      were included. A ten-fold reduction of NaCl in the cultivation media
      significantly reduced the survival fraction of the EGDe strain in the IVD model
      while one of the clinical outbreak isolates showed a significantly increased
      survival fraction. Finally, the EGDe strain was able to attach and invade
      cultured HT-29 cells after passage through the IVD model. Altogether, these
      results suggest that a reduction of the NaCl content from 5 to 0.5% prior to
      exposure to the IVD model has the potential to cause a change in the relative
      survival fraction and that the effect is strain dependent.

PMID- 30297060
TI  - Development and application of a real-time polymerase chain reaction method for
      quantification of Escherichia coli in oysters (Crassostrea gigas).
AB  - Oysters are important mariculture species worldwide. Because of their filter
      feeding behaviors, oysters can accumulate microorganisms, including pathogens,
      from surrounding water and concentrate bacteria in high numbers. Rapid and
      suitable methods for quantification of Escherichia coli in oysters are necessary
      considering that oysters are perishable foods often consumed raw and some
      countries use E. coli as the regulatory limit. The objective of this study was to
      develop a qPCR method for quantification of E. coli in oysters. Additionally,
      different methods were evaluated for DNA extraction from oyster samples and the
      more reliable method was chosen. Primers and probe were designed targeting uidA
      gene of E. coli and shown to specifically amplify DNA from E. coli. Standard
      curves with bacterial DNA extracted from oysters samples artificially inoculated
      with E. coli were conducted. A good correlation was noticed when the qPCR method
      was compared to a culture method in oyster samples. This is the first report of a
      method exclusively developed for direct quantification of E. coli in oyster, the
      method showed to be suitable for quantification of E. coli in oysters and could
      be useful in routine analyses, as it requires less time than the culture method.

PMID- 30297061
TI  - Synthesis of prebiotic galactooligosaccharides from lactose and lactulose by
      dairy propionibacteria.
AB  - The potential of probiotic bacteria to produce prebiotic oligosaccharides by
      transgalactosylation has been minimally studied. In this work, we screened the
      beta-galactosidase (beta-gal) activity of dairy propionibacteria (PAB) isolated
      from Argentinean foods to select strains for the synthesis of oligosaccharides
      from lactose (GOS) and lactulose (OsLu). PAB, when grown in a medium with lactose
      as a carbon source, were disrupted, and the cell-free extracts were assayed for
      beta-gal activity. Nine strains grew on lactose and showed beta-gal activities
      from 0.27 to 2.60 U mL-1. Propionibacterium acidipropionici LET 120, the strain
      with the highest activity, was able to synthesize, using 30% lactose and
      lactulose at pH 6.5 and 45  degrees C, 26.8% of LET 120-GOS and 26.1% of LET 120
      OsLu after 24 h. When they were tested as carbon sources for growth, P.
      acidipropionici LET 120 attained higher biomasses, MUmax and beta-gal activities
      at the expense of Aspergillus oryzae-OsLu, Vivinal(r)-GOS and lactulose compared
      to lactose or glucose. In addition, LET 120-GOS and LET 120-OsLu synthesized by
      PAB were prebiotic for some probiotic strains. For the first time, our results
      show the production of GOS and OsLu by dairy PAB, and these results encourage
      further studies on the optimization of the synthesis and structure
      characterization of the obtained oligosaccharides.

PMID- 30297062
TI  - The Evolution of Mechanical Circulatory Support.
AB  - The field of mechanical circulatory support (MCS) has evolved from earlier
      generation pulsatile-flow devices that were primarily used to support critically
      ill patients in the hospital to newer-generation continuous-flow devices that
      permit hospital discharge and resumption of normal life activities. The
      technology is used to bridge transplant-eligible patients and can be used for
      long-term support of patients who are transplant ineligible. Left ventricular
      assist devices are proved to improve long-term survival and quality of life for
      patients with advanced heart failure. Adverse events associated with MCS therapy
      remain the Achilles heel of the field and strategies to improve biocompatibility
      are ongoing.

PMID- 30297063
TI  - Continuous-Flow Device Engineering and Pump Technology.
AB  - This article on continuous-flow device technology engages in an in-depth
      discussion on the engineering aspects of continuous-flow devices. The authors
      examine the energy transfer mechanics of centrifugal versus axial devices, and
      the impact of novel noncontact pump bearings. Furthermore, this article reviews
      the relationship between continuous-flow pump speed, flow, and pressure gradients
      across the device. Potential future advances in pump design with greater
      algorithmic responses to changes in patient physiology are also considered.

PMID- 30297064
TI  - Surgical Implantation of Intracorporeal Devices: Perspective and Techniques.
AB  - Surgical maneuvers for implantation of a continuous-flow ventricular assist
      device are revolutionary concepts that have been associated with a reduction in
      pump-related complications. With the advancement of technology, surgical implant
      strategy continues to evolve, incorporating less-invasive approaches into the
      armamentarium of the experienced surgeon.

PMID- 30297065
TI  - Temporary Circulatory Support and Extracorporeal Membrane Oxygenation.
AB  - Cardiogenic shock (CS) refractory to conventional therapies continues to be a
      challenging medical syndrome, with poor prognosis and high complication and
      mortality rates. The application and use of temporary mechanical circulatory
      support (MCS) is a component in the treatment of CS patients and should be
      applied early in the presentation. Crucial to the success of their application,
      temporary MCS devices should be chosen based on degree of patient acuity and
      etiology of CS. Not all temporary MCS devices deliver the same degree of
      hemodynamic support and range from minimal support to systemic support via veno
      arterial extracorporeal membrane oxygenation.

PMID- 30297066
TI  - Candidate Selection for Durable Mechanical Circulatory Support.
AB  - Severe systolic dysfunction combined with symptoms of heart failure has a high
      rate of morbidity and mortality. Medical management remains the mainstay of
      therapy but mechanical circulatory support (MCS) is one of the treatment options
      for end-stage heart failure. The left ventricular assist device (LVAD) is the
      most common type of device used for durable MCS. There have been significant
      improvements in the technology, surgical technique, and patient management. There
      is not a single model that is able to accurately assess risk in these patients
      due to the variety of variables. It is essential to assess all risk in the
      decision-making process.

PMID- 30297067
TI  - Perioperative Management of the Right and Left Ventricles.
AB  - Left ventricular assist devices (LVADs) improve survival in select advanced heart
      failure patients and rates of LVAD implantation are growing. LVAD support carries
      significant morbidity and mortality with the greatest risk in the perioperative
      period. Strategies have evolved to minimize this risk. Medical and mechanical
      support is used for right and left ventricular optimization. Other strategies
      emphasize improving nutrition, hematologic abnormalities, infection risk, and
      renal function. Intraoperative approaches highlight anesthesia-related issues,
      management of concomitant valve disease, right ventricular failure, and weaning
      from cardiopulmonary bypass. Postoperative efforts concentrate on augmenting
      right ventricular function, supporting end-organ recovery, and quickly
      identifying complications.

PMID- 30297068
TI  - Ventricular Assist Device Infections.
AB  - This article reviews the diagnostic criteria for ventricular assist device (VAD)
      infection, pathogenesis, and microbiology as well as the diagnostic pathway when
      patients present with signs and symptoms concerning for VAD infection.
      Recommendations regarding infection prevention and management are reviewed as
      well.

PMID- 30297069
TI  - Continuous-Flow Left Ventricular Assist Device-Related Gastrointestinal Bleeding.
AB  - Continuous-flow (CF) left ventricular assist devices (LVADs) are a safe and
      durable therapeutic option for patients with advanced heart failure as a bridge
      to transplant or as destination therapy. Despite the remarkable technological
      advances in device design and increasing familiarity with the physiologic effects
      of CF, major complications such as gastrointestinal bleeding (GIB) continue to
      cause significant morbidity. The causes underlying CF-LVAD-related GIB are
      multifactorial. Accordingly, management strategies for CF-LVAD-related GIB
      encompass a wide range of therapeutic modalities. This article reviews the
      epidemiology, pathophysiology, risk factors, and treatment options for the
      management of this complex complication.

PMID- 30297070
TI  - Neurologic Events in Continuous-Flow Left Ventricular Assist Devices.
AB  - Although the growing use of continuous-flow left ventricular assist devices
      (LVADs) has improved the survival and quality of life of patients with stage D
      heart failure, ischemic and hemorrhagic cerebrovascular accidents remain one of
      the most-feared complications of this therapy and a significant source of
      disability, morbidity, and mortality. In this article, the authors aim to
      summarize the current data regarding the incidence/prevalence of both ischemic
      and hemorrhagic stroke in patients with continuous-flow LVADs, compare axial and
      centrifugal devices, and discuss the major risk factors for neurologic events
      that have been identified.

PMID- 30297071
TI  - Antithrombotic Strategies and Device Thrombosis.
AB  - Despite improvements in left ventricular assist device (LVAD) technology,
      bleeding and thrombotic complications are major concerns that adversely influence
      morbidity and mortality. Current antithrombotic therapy recommendations for LVAD
      thrombosis prophylaxis are largely derived from clinical device trials that
      implement a one-size-fits-all strategy. Objective serial laboratory-based
      assessment of thrombogenicity is needed to balance the risk of bleeding and
      thrombotic complications. Finally, the newest-generation device, the HeartMate 3,
      has been associated with lower levels of shear and reduced hemolysis that may
      mitigate thrombotic event occurrences.

PMID- 30297072
TI  - Impact of Mechanical Circulatory Support on Posttransplant Outcomes.
AB  - Mechanical circulatory support (MCS) has markedly improved the likelihood of
      transplant among patients with advanced heart failure. Transplant survival
      following MCS is similar for supported and unsupported recipients. Transplant
      survival is only reduced following left ventricle assist device (LVAD) support
      complicated by infection, total artificial heart support, and extracorporeal life
      support. Despite allosensitization and a higher incidence of vasoplegia syndrome,
      posttransplant survival for durable LVADs is similar to patients with inotropes
      alone at the time of transplant. MCS as a bridge to transplant offers significant
      benefits over waiting without support.

PMID- 30297074
TI  - Ambulatory Ventricular Assist Device Patient Management.
AB  - Understanding the ventricular assist device (VAD) patient pump interface and
      developing expertise in monitoring patients with a VAD are the goals of care in
      the ambulatory setting. The objective is to improve long-term outcomes. The
      purpose of expert, focused, routine outpatient surveillance is to facilitate the
      integration of pulseless, electrically dependent VAD patients into the community.
      Other goals of outpatient care include maximizing quality of life, maintaining
      equipment integrity, treating heart failure symptoms, monitoring for common VAD
      related complications, ensuring viability as a heart transplant candidate,
      consideration for patients implanted to become transplantable, and monitoring for
      possible cardiac recovery.

PMID- 30297073
TI  - Hemodynamic Pump-Patient Interactions and Left Ventricular Assist Device Imaging.
AB  - Left ventricular assist devices (LVAD) provide a durable option for patients with
      advanced hear failure. Axial and centrifugal pump physiology differs with regard
      to the relationship between pump inflow-outflow cannula pressure differential and
      flow, which results in device behavior that can vary drastically under different
      loading conditions. Ramp studies can aid the clinician in choosing the optimal
      speed to adequately unload the left ventricle. Advances in 3-dimensional
      echocardiography enhance the understanding of chamber geometry for both types of
      LVADs. Novel outflow graft imaging techniques have been developed to better
      characterize aortic insufficiency, which may be underestimated with current
      standard methods.

PMID- 30297075
TI  - A Comprehensive Imaging Approach to Guide the Management of Patients with
      Continuous-Flow Left Ventricular Assist Devices.
AB  - Recent advances in mechanical circulatory support have allowed patients with end
      stage heart failure to be successfully bridged to heart transplantation or live
      for many years on continuous-flow left ventricular assist devices (CF-LVADs) as
      destination therapy. As survival and quality of life continue to improve and the
      number of patients supported by CF-LVADs continues to grow, utilization of
      different imaging modalities in the care for these patients has become an
      integral part of many heart failure centers. We review currently available
      imaging modalities, with a focus on echocardiography, that aid to diagnose and
      manage common adverse events associated with CF-LVADs.

PMID- 30297076
TI  - Right Ventricular Failure and Biventricular Support Strategies.
AB  - Some degree of right ventricular (RV) dysfunction can be observed in most
      patients with advanced heart failure assed for left ventricular assist device
      (LVAD) implantation. This article describes critical factors that need to be
      considered in the assessment of the RV before LVAD surgery. Further, detailed
      description of the most important perioperative management strategies to prevent
      (RV) dysfunction is included. Finally, the most commonly used temporary and
      permeant RV support strategies are discussed, including anatomic and physiologic
      challenges and barriers associated with the off-label use of continuous-flow LVAD
      pumps for the right-sided circulation.

PMID- 30297077
TI  - Defining a Decade of Experience with Continuous-Flow Left Ventricular Assist
      Devices.

PMID- 30297078
TI  - [How to manage anticoagulation in atrial fibrillation ablation].
AB  - There are many randomized trials evaluating non-vitamin K oral anticoagulants
      (NOAC) in patients with atrial fibrillation ablation. VENTURE AF, RE-CIRCUIT, and
      recently AXAFA have evaluated the three main NOACs in this indication. Other
      studies such as ABRIDGE J and AEIOU complemented these results. The management of
      the anticoagulation in these patients is one of the subjects of the European
      Society of Cardiology guidelines, as well, as, the EHRA guide recently released.
      The purpose of this article is to summarize published studies and guidelines.

PMID- 30297079
TI  - Tribute to Dr Gorm Wagner, Founding Father of ISSM.

PMID- 30297080
TI  - Corrigendum to: Ultrasound-guided subacromial-subdeltoid bursa corticosteroid
      injections: a study of short- and long-term outcomes [Clin Radiol 73 (8)(2018) e7
      e12].

PMID- 30297081
TI  - Isolation and characterization of a marine testosterone-degrading bacterium:
      Vibrio sp. N3.
AB  - Steroids, including testosterone, estrone, 17beta-estradiol, estriol and 17beta
      ethinyl estradiol, are harmful not only to the population dynamics of aquatic
      life forms but also to public health. In this study, a marine testosterone
      degrading bacterium (strain N3) was isolated from Nanao Island in the South China
      Sea. In addition, the strain could also use 17beta-estradiol (E2), 17beta-ethinyl
      estradiol (EE2), estriol (E3) or cholesterol as a sole carbon source. According
      to the 16S rRNA gene sequence analysis, strain N3 was identified as Vibrio sp.
      Further characterization showed that the strain is aerobic, gram-negative, and
      mobile and exhibits resistance to ampicillin, carbenicillin, penicillin and
      spectinomycin. For enhancing its capacity of testosterone degradation, the
      Plackett-Burman factorial design and the central composite design were used to
      optimize the culture condition. Under optimal conditions, 92% of testosterone was
      degraded by Vibrio sp. N3 in 48h.

PMID- 30297082
TI  - The Role of Vitamin D in CKD Stages 3 to 4: Report of a Scientific Workshop
      Sponsored by the National Kidney Foundation.
AB  - Deficiency of 25-hydroxyvitamin D (25[OH]D) is common in patients with chronic
      kidney disease stages 3 and 4 and is associated with poor outcomes. However, the
      evaluation and management of vitamin D deficiency in nephrology remains
      controversial. This article reports on the proceedings from a "controversies
      conference" on vitamin D in chronic kidney disease that was sponsored by the
      National Kidney Foundation. The report outlines the deliberations of the 3 work
      groups that participated in the conference. Until newer measurement methods are
      widely used, the panel agreed that clinicians should classify 25(OH)D "adequacy"
      as concentrations > 20ng/mL without evidence of counter-regulatory hormone
      activity (ie, elevated parathyroid hormone). The panel also agreed that 25(OH)D
      concentrations < 15ng/mL should be treated irrespective of parathyroid hormone
      level. Patients with 25(OH)D concentrations between 15 and 20ng/mL may not
      require treatment if there is no evidence of counter-regulatory hormone activity.
      The panel agreed that nutritional vitamin D (cholecalciferol, ergocalciferol, or
      calcifediol) should be supplemented before giving activated vitamin D compounds.
      The compounds need further study evaluating important outcomes that observational
      studies have linked to low 25(OH)D levels, such as progression to end-stage
      kidney disease, infections, fracture rates, hospitalizations, and all-cause
      mortality. We urge further research funding in this field.

PMID- 30297083
TI  - Urine Acidification After Ammonium Chloride.

PMID- 30297084
TI  - Visualizing immune responses of the airway mucosa.
AB  - The airway mucosa is the primary tissue site exposed to inhaled particulate
      matter, which includes pathogens and allergens. While most inhaled particles are
      eliminated from the airways via mucociliary clearance, some pathogens may
      penetrate the mucosal epithelial barrier and an effective activation of the
      mucosal immune system is required to prevent further pathogen spread. Similarly,
      inhaled environmental allergens may induce an aberrant activation of immune cells
      in the airway mucosa, causing allergic airway disease. During the last years,
      several investigators employed advanced microscopic imaging on both intravital
      and tissue explant preparations to observe the dynamic behavior of various immune
      cells within their complex tissue environment. In the respiratory tract, most
      imaging studies focused on immune responses of the alveolar compartment in the
      lung periphery. However, equally important immunological events occur more
      proximally in the mucosa of the conducting airways, both during infection and
      allergic responses, calling for a more detailed imaging analysis also at this
      site. In this review, I will outline the technical challenges of designing
      microscopic imaging experiments in the conducting airways and summarize our
      recent efforts in understanding airway mucosal immune cell dynamics in steady
      state conditions, during infection and allergy.

PMID- 30297085
TI  - Efficient Neural Coding in Auditory and Speech Perception.
AB  - Speech has long been recognized as 'special'. Here, we suggest that one of the
      reasons for speech being special is that our auditory system has evolved to
      encode it in an efficient, optimal way. The theory of efficient neural coding
      argues that our perceptual systems have evolved to encode environmental stimuli
      in the most efficient way. Mathematically, this can be achieved if the optimally
      efficient codes match the statistics of the signals they represent. Experimental
      evidence suggests that the auditory code is optimal in this mathematical sense:
      statistical properties of speech closely match response properties of the
      cochlea, the auditory nerve, and the auditory cortex. Even more interestingly,
      these results may be linked to phenomena in auditory and speech perception.

PMID- 30297086
TI  - Always keep an open mind.

PMID- 30297088
TI  - Surgical ablation explained.

PMID- 30297087
TI  - Bioprosthesis in young patients: A reality or a fantasy.

PMID- 30297089
TI  - Newer advances, newer challenges?

PMID- 30297090
TI  - From the aorta to the femoral artery and back again: An iconic round trip.

PMID- 30297091
TI  - Ecologically assessed affect and suicidal ideation following psychiatric
      inpatient hospitalization.

PMID- 30297092
TI  - Meropenem heteroresistance in clinical isolates of OXA-48-producing Klebsiella
      pneumoniae.
AB  - OXA-48-producing Klebsiellapneumoniae isolates often show growth of colonies
      within inhibition zones in carbapenem diffusion assays. The nature of these
      colonies was investigated in a series of clinical isolates of OXA-48-producing K.
      pneumoniae obtained in the context of a hospital outbreak, and they were found to
      be persistent colonies that reproduced again the same phenotype when they were
      collected and tested in diffusion assays again. The frequency of mutations
      conferring resistance to meropenem (8 MUg/mL) was determined for the same
      isolates. The average mutation frequency was 5.47.10-6 (range: 2.59.10-8-5.87.10
      5), and the analysis of several resistant mutants showed that all of them had
      mutations in the ompK36 porin gene. Heteroresistance was investigated using
      population analysis profiling. The profiles were compatible with mutation
      frequency assays, and all the colonies analyzed were resistant mutants. In OXA-48
      producing K. pneumoniae, the growth of persisters seems to be specific of
      diffusion assays.

PMID- 30297094
TI  - Mindfulness-Based Group Therapy for Men With Situational Erectile Dysfunction: A
      Mixed-Methods Feasibility Analysis and Pilot Study.
AB  - INTRODUCTION: Recent advances in sexual health research support the benefits of
      mindfulness-based therapy (non-judgmental present-moment awareness) for the
      treatment of women's sexual dysfunction. AIM: To determine whether it is feasible
      to implement an adapted, empirically supported treatment protocol for female
      sexual dysfunction to the specific needs of men with situational erectile
      dysfunction (ED). METHODS: A mixed-methods approach was taken for this
      feasibility pilot study. A total of 10 men (Mage = 40.3, SD = 14.01, Range = 20
      67) with a diagnosis of situational ED were recruited to participate in a 4-week
      mindfulness-based treatment group. The group was adapted from protocols shown to
      be effective for women with sexual dysfunction and edited to include content
      specific to situational ED. Sessions were 2.25 hours in length, included daily
      home-practice activities, and integrated elements of psychoeducation, sex
      therapy, and mindfulness skills. Men completed questionnaires (International
      Index of Erectile Functioning, Relationship Assessment Scale, Five Facets of
      Mindfulness Questionnaire, a treatment expectation questionnaire) at 3 time
      points (prior to treatment, immediately after treatment, and 6 months after
      treatment). 5 men (Mage = 44.4, SD = 15.76, Range = 30-67) participated in
      qualitative exit interviews. MAIN OUTCOME MEASURE: Findings support the
      feasibility of adapting a mindfulness-based group treatment for situational ED.
      RESULTS: With respect to feasibility, the dropout rate was 10%, with 1
      participant who did not complete the treatment. Comparisons between Time 1 and
      Time 3 self-reports suggested that this treatment protocol holds promise as a
      novel means of impacting erectile functioning (Cohen's d = 0.63), overall sexual
      satisfaction (Cohen's d = 1.02), and non-judgmental observation of one's
      experience (Cohen's d = 0.52). Participants' expectations for the treatment were
      generally positive and correlated to self-reported outcomes (r = .68-.73).
      Qualitative analyses revealed 6 themes: normalization, group magic,
      identification of effective treatment targets, increased self-efficacy,
      relationship factors, and treatment barriers. CLINICAL IMPLICATIONS: In a shift
      toward a biopsychosocial framework for the treatment of men's sexual dysfunction,
      clinicians may consider incorporating mindfulness to address psychosocial and
      psychosexual components of dysfunction. STRENGTH & LIMITATIONS: This is the first
      study-to our knowledge-to adapt mindfulness protocols for use with men's sexual
      dysfunction. Because this is a pilot study aimed at feasibility, the sample size
      is small and no control group was included, thus conclusions about efficacy and
      generalizability cannot be made. CONCLUSION: The current study suggests that a
      mindfulness group therapy framework offers a feasible and potentially promising
      treatment avenue for men with situational ED. Bossio JA, Basson R, Driscoll M, et
      al. Mindfulness-based group therapy for men with situational erectile
      dysfunction: A mixed-methods feasibility analysis and pilot study. J Sex Med
      2018;15:1478-1490.

PMID- 30297093
TI  - Best Practices in North American Pre-Clinical Medical Education in Sexual History
      Taking: Consensus From the Summits in Medical Education in Sexual Health.
AB  - INTRODUCTION: This article discusses a blueprint for a sexual health
      communication curriculum to facilitate undergraduate medical student acquisition
      of sexual history taking skills and includes recommendations for important
      elements of a thorough sexual history script for undergraduate medical students.
      AIM: To outline the fundamentals, objectives, content, timing, and teaching
      methods of a gold standard curriculum in sexual health communication. METHODS:
      Consensus expert opinion was documented at the 2012, 2014, and 2016 Summits in
      Medical Education in Sexual Health. Additionally, the existing literature was
      reviewed regarding undergraduate medical education in sexual health. MAIN OUTCOME
      MEASURES: This article reports expert opinion and a review of the literature on
      the development of a sexual history taking curriculum. RESULTS: First-year
      curricula should be focused on acquiring satisfactory basic sexual history taking
      skills, including both assessment of sexual risk via the 5 Ps (partners,
      practices, protection from sexually transmitted infections, past history of
      sexually transmitted infections, and prevention of pregnancy) as well as
      assessment of sexual wellness-described here as a sixth P (plus), which
      encompasses the assessment of trauma, violence, sexual satisfaction, sexual
      health concerns/problems, and support for gender identity and sexual orientation.
      Second-year curricula should be focused on incorporating improved clinical
      reasoning, emphasizing sexual history taking for diverse populations and
      practices, and including the impact of illness on sexual health. Teaching methods
      must include varied formats. Evaluation may be best as a formative objective
      structured clinical examination in the first year and summative in the second
      year. Barriers for curriculum development may be reduced by identifying faculty
      champions of sexual health/medicine. CLINICAL IMPLICATIONS: Medical students will
      improve their skills in sexual history taking, which will ultimately impact
      patient satisfaction and clinical outcomes. Future research is needed to validate
      this proposed curriculum and assess the impact on clinical skills. STRENGTHS &
      LIMITATIONS: This article assimilates expert consensus and existing clinical
      guidelines to provide a novel structured approach to curriculum development in
      sexual health interviewing in the pre-clinical years. CONCLUSION: The blueprint
      for developing sexual history taking skills includes a spiral curriculum with
      varied teaching formats, incorporation of a sexual history script that
      incorporates inquiry about sexual wellness, and longitudinal assessment across
      the pre-clinical years. Ideally, sexual health communication content should be
      incorporated into existing clinical interviewing and physical examination
      courses. Rubin ES, Rullo J, Tsai P, et al. Best Practices in North American Pre
      Clinical Medical Education in Sexual History Taking: Consensus From the Summits
      in Medical Education in Sexual Health. J Sex Med 2018;15:1414-1425.

PMID- 30297095
TI  - Higher notch expression implies poor survival in pancreatic ductal
      adenocarcinoma: A systematic review and meta-analysis.
AB  - BACKGROUND: At present, pancreatic ductal adenocarcinoma (PDAC) is a fetal
      disease lack of effective prognostic and therapeutic methods resulting in high
      mortality. The Notch signaling has been demonstrated being up- or down-regulated
      in many cancers, but the effects in pancreatic ductal adenocarcinoma are still
      controversial. Moreover, the available cases in an individual study are of small
      samples. Therefore, it is essential to define the effect of Notch signaling in
      pancreatic ductal adenocarcinoma with larger samples. METHODS: Conducted from 6
      eligible studies and 463 pancreatic ductal adenocarcinoma patients, this was the
      first meta-analysis to analyze the correlation between the Notch signal pathway
      and pancreatic ductal adenocarcinoma. All data were sourced from The National
      Center for Biotechnology Information, Web of Science and Cochrane. The articles
      which matched the inclusion criteria were included. All included data were
      analyzed and performed by Review Manager 5.3. RESULTS: The results indicated that
      high expression of Notch signaling proteins was associated with poor overall
      survival of pancreatic ductal adenocarcinoma patients (pooled hazard ratio>2.00;
      P < 0.001). Moreover, poor survival was related to high expression of Notch3
      (pooled hazard ratio: 2.05; confidence interval: 1.49-2.82; P < 0.001) and DLL4
      (pooled hazard ratio: 2.13; confidence interval: 1.37-3.32; P < 0.001).
      CONCLUSIONS: This meta-analysis supports that Notch signaling proteins may be
      available as prognostic factors for pancreatic ductal adenocarcinoma progression
      and patient survival. Higher expression of Notch signaling proteins indicated
      poor survival of pancreatic ductal adenocarcinoma patients. Targeting Notch
      signaling components, especially Notch3 protein, would be beneficial for
      therapies.

PMID- 30297096
TI  - Usefulness of serum biopterin as a predictive biomarker for childhood asthma
      control: A prospective cohort study.
AB  - BACKGROUND: Pteridines are metabolites of tetrahydrobiopterin, which serves as co
      enzyme of nitric oxide synthase. We sought to investigate the usefulness of
      pteridines as biomarkers for childhood asthma control. METHODS: We conducted a
      single-center prospective cohort study involving 168 asthmatic children aged 4-17
      years who visited the periodical asthma checkup program. Serum neopterin and
      biopterin levels were measured as pteridines at each visit along with measurement
      of FeNO, respiratory function tests, nasal eosinophil test, blood eosinophil
      count, and IgE level. We calculated coefficients for relation between pteridines
      and asthma control, which was assessed by questionnaires (JPAC: Japanese
      Pediatric Asthma Control Program). RESULTS: A total of 168 participants aged 10.3
      +/- 3.39 years (mean +/- SD) with asthma were recruited. The participants in this
      study contained 58 patients (34.5%) of complete-controlled based on JPAC, 132
      patients (76.0%) of well-controlled group based on GINA. FeNO and serum neopterin
      level did not correlate with following period's JPAC scores. In contrast, serum
      biopterin level significantly correlated with following period's JPAC total score
      (Coefficients 0.398; 95% CI 0.164 to 0.632; p value 0.001) and frequency of
      wheezing during exercise (Coefficients 0.272; 95% CI 0.217 to 0.328; p value <
      0.001). CONCLUSIONS: We found serum biopterin effected the following period's
      control status of asthmatic children, thus monitoring biopterin level will be a
      useful for management of asthma to adjust treatment.

PMID- 30297097
TI  - Challenges of imaging injured Paralympic Athletes.
AB  - The pattern and mechanism of sports injuries in disabled athletes and the
      challenges to overcome such injuries is well documented. However, there is
      limited information regarding the specifics of medical imaging of the injured
      disabled athletes. This article, reflects on the experience gained during the
      organisation and provision of the imaging services for the London 2012 Paralympic
      games. The knowledge gained during these games, in conjunction with information
      from the existing literature on sporting injuries in disabled athletes can help
      planning and delivery of well-coordinated imaging services at major disability
      sporting events.

PMID- 30297098
TI  - [What is the role of the comprehensive geriatric assessment in Geriatric
      Oncology?]
AB  - The growing increase in world population and generalised aging have been
      accompanied by an increase in the prevalence of cancer in the elderly. Aging is
      associated with certain physiological changes, some of which are enhanced by the
      neoplasm itself. Along with this, the elderly oncology patient usually has more
      problems than the rest of the elderly, and has a multitude of deficits. These
      characteristics require a special handling of the older patient with cancer, by
      using the main tool used in Geriatrics, the comprehensive geriatric assessment.
      This article analyses the importance of the comprehensive geriatric assessment in
      this population group, paying special attention to its ability to predict the
      toxicity of chemotherapy and the survival of the elderly oncology, as well as its
      ability to classify these patients into groups that help in the decision making
      process.

PMID- 30297099
TI  - Electroencephalogram findings in patients with posterior cortical atrophy.
AB  - AIM OF THE STUDY: The aim of this study is to evaluate standard scalp EEG
      findings in patients with posterior cortical atrophy (PCA), an atypical variant
      of Alzheimer's disease (AD). CLINICAL RATIONALE: PCA is a topographically
      selective variant of AD. Patients with typical AD have an increased likelihood of
      seizures, which may negatively impact overall functional performance and
      cognition. It is currently unknown what the typical EEG findings are for patients
      with PCA. MATERIALS AND METHODS: A retrospective chart review was performed on
      patients identified either with autopsy confirmed (n=13) or clinically (n=126) as
      PCA. RESULTS: 139 patients were included though only 23 (16.5%) had undergone EEG
      recording. The EEG was normal in 6 (26%), while an abnormal EEG was present in 17
      (74%). Interictal epileptic discharges (IEDs) were found in 2 of the 23 patients
      (9%). CONCLUSIONS: This study of limited sample size suggests that there may be
      an increased predilection to find IEDs within PCA when compared to typical AD.
      Larger cohorts are required to determine frequency of abnormal EEGs in PCA, roles
      of AEDs in therapy, and in the selection of preferred AED. CLINICAL IMPLICATIONS:
      Patients with PCA would potentially benefit from an EEG for assessment of IEDs
      which may provide the clinician with a therapeutic opportunity.

PMID- 30297100
TI  - Characteristics and clinical correlates of white matter changes in brain magnetic
      resonance of migraine females.
AB  - OBJECTIVE: White matter hyperintensities (WMHs) were often found in migraine
      patients. The aim of study was to characterize WMHs, assess their prevalence,
      determine relationship to clinical symptoms and homocysteine levels in migraine
      females. METHODS: 69 women 38 with migraine without aura (MO), 31 with migraine
      with aura (MA) who underwent brain MRI with 1.5T scanner were enrolled. The WMHs
      number, location and size in FLAIR sequence were evaluated. Migraine severity was
      measured by pain intensity, number of attacks per month and MIDAS scale. RESULTS:
      WMHs were found in 39.1% females. There was no WMHs and migraine type
      correlation. The total WMHs number was higher in MO (p=0.027). Patients with WMHs
      were older (p=0.025), have higher BMI (p=0.042), suffered longer (p=0.001), more
      often had positive pregnancy history (p=0.010) and less frequent prodromal
      symptoms. The age of onset, migraine's severity and homocysteine did not
      correlate with WMHs. No effect of antimigraine medication and oral contraceptive
      pills (OCP) was found. Both in MO and MA groups WMHs were located only
      supratentorially. In MO females WMHs were mainly located in one cerebral
      hemisphere (p=0.024) whereas in MA were found bilaterally. WMHs were most
      commonly located in the frontal lobes. In MO lesions were small <=3mm and present
      in almost all MO patients (p=0.027). CONCLUSION: WMHs are present in more than
      one third of migraine females, regardless of aura. WHMs are located
      supratentorially, subcortically and in the frontal lobes. Older age, longer
      disease's duration, obesity and positive history of pregnancy are main risk
      factors for WMHs. Symptomatology and migraine severity, hyperhomocysteinemia, OCP
      and anti-migraine medications do not increase WMHs.

PMID- 30297101
TI  - Reduction of Risk Factors for Pedophilic Sexual Offending.
AB  - INTRODUCTION: Exploratory analysis of characteristics and reduction of risk
      factors for child sexual abuse (CSA) in a sample treated in the Prevention
      Projects Dunkelfeld Hannover and Regensburg. AIM: To evaluate a treatment program
      aimed at reducing dynamic risk factors (DRF) for CSA. METHODS: Using a
      psychometric test battery based on self-report questionnaires, intergroup
      analysis between treatment group (TG, n = 35), treatment refusers (TR, n = 51),
      and drop-out group (DO, n = 14) was conducted with pretreatment data. Intragroup
      analysis compared data of TG from pre- and posttreatment. The test battery
      included sociodemographic and sociosexual data, as well as questionnaires
      measuring DRF. MAIN OUTCOME MEASURE: This study investigated effects of treatment
      on pedophilic men who are at risk for offending and observed reductions in
      important risk factors for CSA. RESULTS: TG, TR (consisting of persons who were
      offered but refused therapy), and DO did not differ regarding sociodemographic
      and sociosexual variables before therapy. There were no significant differences
      in education, relationship status, living solitarily, and being a
      father/stepfather. TR and DO lived farther away from treatment site than TG. In
      the TG, a reduction in offense-supportive attitudes, coping self-efficacy
      deficits, and child identification were revealed at second assessment. In TG no
      participants started the consumption of child abuse content during the course of
      the study. CLINICAL IMPLICATIONS: Future treatment concepts should focus on the
      reduction of empirically relevant risk factors for child sexual offending.
      STRENGTH & LIMITATIONS: The present article is the first that compares TG to TR
      and DO before assessment regarding DRF and sociosexual variables. Moreover, it is
      only the second study that investigated treatment effects on a population of
      pedophilic men who are at risk for offending. These preliminary findings are
      limited by moderate group size and a missing control group. CONCLUSION: A
      reduction in some but not all assessed risk factors for sexual offending against
      minors could be seen within the time frame of therapy. Findings are in line with
      results from a previous evaluation study. Engel J, Korner M, Schuhman P.
      Reduction of risk factors for pedophilic sexual offending. J Sex Med 2018;15:1629
      1637.

PMID- 30297102
TI  - Effectiveness of Recurrence Quantification Measures in Discriminating Subjects
      With and Without Voice Disorders.
AB  - The objective of this study was to analyze the accuracy of recurrence
      quantification measurements (RQMs) in discriminating between individuals with and
      without voice disorders. This study consisted of a total of 541 recorded voice
      samples from normal and dysphonic subjects. All subjects recorded a sustained
      vowel /E/ and underwent a laryngoscopic examination of the larynx. Twelve RQMs
      and three parameters related to the topology of the phonatory system were
      extracted from the samples, for a total of 15 measures. The classification used
      quadratic discriminant analysis and includes the measures of accuracy,
      sensitivity, and specificity. Single measurements such as Shannon's entropy,
      average diagonal length, and transitivity had only acceptable performance ratings
      (>=70%) in discriminating between individuals with and without voice disorders.
      The combination of the parameters average diagonal length, Shannon's entropy,
      trapping time, length of the longest vertical line, tau, imbedding dimension,
      neighborhood radius, and transitivity produced the highest accuracy in
      discrimination (83.27%). Therefore, the performance of RQMs related to the
      formation of diagonal lines in classifying individuals with and without voice
      disorders was acceptable at >=70%. A combination of RQMs showed good performance
      in discriminating between the study groups, with higher sensitivity and
      specificity.

PMID- 30297103
TI  - Maturation and fertilization of echinoderm eggs: Role of actin cytoskeleton
      dynamics.
AB  - Starfish and sea urchin are excellent models to study the mechanisms that
      regulate oocyte maturation and egg activation. Hormonal stimulation of starfish
      oocytes and their following interaction with spermatozoa induce rapid changes of
      F-actin and Ca2+ increases which are prerequisites for normal fertilization and
      development. Fully grown oocytes isolated from the gonads of starfish contain a
      large nucleus (~60-70 MUm) (termed germinal vesicle, GV), which is arrested at
      the first prophase of meiosis. If inseminated, these immature oocytes are
      penetrated by additional spermatozoa. However, starfish oocytes naturally shed
      into the sea have already initiated the (meiotic) maturation and are normally
      fertilized between GV breakdown and the extrusion of the first polar body. This
      is considered the optimum period to ensure monospermic instead of polyspermic
      fertilization. By contrast, sea urchin eggs are fertilized only after being fully
      matured, i.e., at the end of the two meiotic divisions. Here, we provide a
      comparative review of the role of the actin cytoskeleton in oocyte maturation and
      fertilization in starfish and sea urchin. It has become increasingly evident that
      the exquisite regulation of the cortical F-actin is involved in nearly all
      aspects of the molecular events taking place during the progression of meiotic
      maturation and fertilization.

PMID- 30297104
TI  - LINC00662 promotes gastric cancer cell growth by modulating the Hippo-YAP1
      pathway.
AB  - Long non-coding RNAs (lncRNAs) function as vital regulators of the progression of
      various diseases, particularly cancers. In the present study, utilizing the
      Cancer Genome Atlas (TCGA) data set and a series of cell experiments and clinical
      tissue samples assays, we found that LINC00662 expression was significantly up
      regulated in gastric cancer (GC) tissues and cell lines. High expression of
      LINC00662 predicted poor prognosis compared to in patients showing low
      expression. Knockdown of LINC00662 expression decreased GC cell proliferation and
      increased the chemo-sensitivity of GC cells. Further, we demonstrated that
      knockdown of LINC00662 suppressed the Hippo-YAP1 signaling pathway in GC cells.
      Mechanistically, LINC00662 regulated YAP1-mediated GC cell proliferation by
      sponging miR-497-5p. Overall, our results revealed a critical role for the
      LINC00662-miR-497-5p-YAP1 axis in GC cell growth, providing a new target for GC.

PMID- 30297105
TI  - Cyclophilin 1 (Cyp1) mutation ameliorates oxidative stress-induced defects in a
      Drosophila DJ-1 null mutant.
AB  - Drosophila cyclophilin 1 (Cyp1) is a structural and functional homolog of
      mammalian cyclophilin D (CypD), a unique mitochondrial cyclophilin (Cyp) that
      regulates the inner mitochondrial membrane permeability transition and cell
      survival under cellular stresses such as oxidative damage. In this study, we
      generated and characterized a Drosophila Cyp1 mutant. Cyp1 mutant flies
      successfully developed into adults and showed no significant defects in
      mitochondrial morphology, function, and content. However, oxidative damage
      significantly decreased in Cyp1 mutant flies, and inhibition of Cyp1 expression
      substantially increased the survival under various oxidative stress paradigms.
      Moreover, Cyp1 mutation successfully ameliorated survival rates, locomotor
      activity, and dopaminergic neuron quantity in a Drosophila DJ-1 mutant under
      oxidative stress, further confirming the protective role of Cyp1 mutation against
      oxidative stress. In conclusion, these results suggest Cyp1 and its human homolog
      CypD as putative molecular targets for the treatment of DJ-1 deficiency
      associated diseases, including Parkinson's disease.

PMID- 30297106
TI  - Gene expression profiling in adipose tissue of Sprague Dawley rats identifies
      olfactory receptor 984 as a potential obesity treatment target.
AB  - The aim of the study was to identify and functionally characterize novel
      candidate gene/s involved in the development of resistance to diet-induced
      obesity in rats. In a high-fat-diet (HFD) study of rats, we found subgroups which
      either developed resistance to HFD-induced obesity (DR) or showed an obesity
      prone phenotype (DIO). Gene expression analysis in 10 samples (5 DIO vs 5 DR) was
      performed. The most promising gene, OR6C3 (orthologous with rat Olr984 and mouse
      Olfr788) was measured by qRT-PCR in paired samples of human visceral (Vis) and
      subcutaneous (SC) adipose tissue (AT) (n = 225) and in sub-fractions of
      adipocytes and cells of stromal vascular fraction. Gene expression analyses
      showed Olr984 with significantly reduced mRNA expression in DR rats. In the Vis
      AT of human samples we found an up-regulation of OR6C3 compared to SC AT,
      independent of gender, glucose tolerance or type 2 diabetes. We observed
      significantly lower levels of SC AT OR6C3 mRNA in subjects with obesity compared
      to those with normal-weight or overweight. OR6C3 is more expressed in SVF than in
      adipocytes. Olr984 could be a novel candidate gene related to diet-induced
      obesity in rats. Variation in human AT mRNA expression is related to obesity
      parameters and glucose homeostasis and linked to the regulatory role of insulin
      on the Olr984.

PMID- 30297107
TI  - The long noncoding RNA XIST protects cardiomyocyte hypertrophy by targeting miR
      330-3p.
AB  - Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are implicated in numerous
      kinds of cardiovascular diseases, and their vital role in regulating cardiac
      hypertrophy still needs to be explored. In this study, we demonstrated that
      lncRNA X-inactive specific transcript (XIST) was upregulated in hypertrophic
      cardiac of mice and phenylephrine (PE)-treated cardiomyocytes. Next, we observed
      that inhibition of XIST induced hypertrophic response of cardiomyocyte and
      overexpression of XIST attenuated cardiomyocyte hypertrophy induced by PE.
      Furthermore, through online predictive tools and functional experiments, we
      demonstrated that XIST and S100B were targets of miR-330-3p. XIST and miR-330-3p
      suppressed each other in a reciprocal way in cardiomyocytes. Additionally, XIST
      promoted S100B expression through harboring the complementary binding sites with
      miR-330-3p, eventually prevented cardiac hypertrophy. In conclusion, our findings
      revealed a novel molecular mechanism that XIST/miR-330-3p/S100B pathway modulates
      the progression of cardiomyocyte hypertrophy.

PMID- 30297108
TI  - A novel derivative (GTN024) from a natural product, komaroviquinone, induced the
      apoptosis of high-risk myeloma cells via reactive oxygen production and ER
      stress.
AB  - New drugs have significantly improved the survival of patients with multiple
      myeloma (MM), but the prognosis of MM patients with high-risk cytogenetic changes
      such as t(4; 14), t(14; 16) or del17p remains very poor. A natural product,
      komaroviquinone (KQN), was originally isolated from the perennial semi-shrub
      Dracocephalum komarovi and has anti-protozoal activity against Trypanosoma cruzi,
      the organism causing Chagas' disease. Here we demonstrate that a novel KQN
      derivative, GTN024, has an anti-MM effect both in vitro and in vivo. GTN024
      induced the apoptosis of MM cell lines including those with high-risk cytogenetic
      changes. GTN024 produced reactive oxygen species (ROS) and increased
      phosphorylated eIF2alpha. The ROS production and subsequent endoplasmic reticulum
      (ER) stress are thought to play a key role in GTN024-induced apoptosis, as the
      apoptosis was completely abrogated by anti-oxidant treatment. In a mouse
      xenograft model, an intraperitoneal injection of 20 mg/kg of GTN024 significantly
      delayed tumor growth. Hematological toxicity and systemic toxicity as indicated
      by weight loss were not observed. These results suggest that the novel KQN
      derivative GTN024 could become a candidate drug for treating high-risk MM.

PMID- 30297109
TI  - Cyclic stretch increases mitochondrial biogenesis in a cardiac cell line.
AB  - Unlike stable and immobile cell line conditions, animal hearts contract and relax
      to pump blood throughout the body. Mitochondria play an essential role by
      producing biological energy molecules to maintain heart function. In this study,
      we assessed the effect of heart mimetic cyclic stretch on mitochondria in a
      cardiac cell line. To mimic the geometric and biomechanical conditions
      surrounding cells in vivo, cyclic stretching was performed on HL-1 murine
      cardiomyocytes seeded onto an elastic micropatterned substrate (10% elongation,
      0.5 Hz, 4 h/day). Cell viability, semi-quantitative Q-PCR, and western blot
      analyses were performed in non-stimulated control and cyclic stretch stimulated
      HL-1 cell lines. Cyclic stretch significantly increased the expression of
      mitochondria biogenesis-related genes (TUFM, TFAM, ERRalpha, and PGC1-alpha) and
      mitochondria oxidative phosphorylation-related genes (PHB1 and CYTB). Western
      blot analysis confirmed that cyclic stretch increased protein levels of
      mitochondria biogenesis-related proteins (TFAM, and ERRalpha) and oxidative
      phosphorylation-related proteins (NDUFS1, UQCRC, and PHB1). Consequently, cyclic
      stretch increased mitochondrial mass and ATP production in treated cells. Our
      results suggest that cyclic stretch transcriptionally enhanced mitochondria
      biogenesis and oxidative phosphorylation without detrimental effects in a
      cultured cardiac cell line.

PMID- 30297110
TI  - Vascular apoptosis associated with meglumine antimoniate: In vivo investigation
      of a chick embryo model.
AB  - The vasculo-toxic effect of meglumine antimoniate (MA) was confirmed in our
      previous investigation. The current study investigates the association of this
      effect with altered VEGF-A and VEGF-R2 expression. Additional mechanisms by which
      MA causes vascular toxicity are not clearly understood. We hypothesized that MA
      may alter normal expression of apoptotic genes and cause vascular toxicity. The
      current investigation was designed to address this issue using a chick embryo
      model. Fertile chicken eggs were treated with MA and the extra-embryonic membrane
      (EEM) vasculature was evaluated by morphometric, molecular and
      immunohistochemistry assays. The results showed that MA not only altered
      apoptotic gene expression, but that this alteration may disturb the normal
      development of the vascular network and cause embryo malformation. The relative
      expression level of the CASP3, CASP7, CASP9, APAF1, AIF1 and TP53 genes increased
      in drug-exposed EEMs. In addition, IHC assay confirmed the low expression BCL2
      and increased expression of Bax, which are associated with a high rate of
      apoptosis. We suggest that induction of an apoptotic signaling pathway can lead
      to vascular defects during embryo development and the consecutive cascade of
      events can lead to the embryo malformation.

PMID- 30297111
TI  - Wucherria bancrofti glutathione S-Transferase: Insights into the 2.3 A resolution
      X-ray structure and function, a therapeutic target for human lymphatic
      filariasis.
AB  - The notoriety of parasitic nematode survival is directly related to chronic
      pathogenicity, which is evident in human lymphatic filariasis. It is a disease of
      poverty which causes severe disability affecting more than 120 million people
      worldwide. These nematodes down-regulate host immune system through a myriad of
      strategies that includes secretion of antioxidant and detoxification enzymes like
      glutathione-S-transferases (GSTs). Earlier studies have shown Wuchereria
      bancrofti GST to be a potential therapeutic target. Parasite GSTs catalyse the
      conjugation of glutathione to xenobiotic and other endogenous electrophiles and
      are essential for their long-term survival in lymph tissues. Hence, the crystal
      structure of WbGST along with its cofactor GSH at 2.3 A resolution was
      determined. Structural comparisons against host GST reveal distinct differences
      in the substrate binding sites. The parasite xenobiotic binding site is more
      substrate/solvent accessible. The structure also suggests the presence of
      putative non-catalytic binding sites that may permit sequestration of endogenous
      and exogenous ligands. The structure of WbGST also provides a case for the role
      of the pi-cation interaction in stabilizing catalytic Tyr compared to
      stabilization interactions described for other GSTs. Hence, the obtained
      information regarding crucial differences in the active sites will support future
      design of parasite specific inhibitors. Further, the study also evaluates the
      inhibition of WbGST and its variants by antifilarial diethylcarbamazine through
      kinetic assays.

PMID- 30297112
TI  - As an independent prognostic factor, USP6 promotes the invasion and metastasis of
      colon cancer.
AB  - The lack of efficient tumor invasion and metastatic biomarkers led to high
      mortality rates in colon cancer patients. Aberrant expression of ubiquitin
      specific protease 6 (USP6) was involved in several diseases including cancer,
      while its role in the progression of colon cancer was still unclear. In this
      study, USP6 was evaluated at both mRNA and protein levels by using RT-PCR,
      western blot and immunohistochemistry staining analyses. The results revealed
      that high USP6 expression predicted poor disease-specific survival and overall
      survival through Kaplan-Meier analyses with log-rank tests, univariate and
      multivariate Cox analyses. Furthermore, cell function assay demonstrated that
      USP6 could promote colon cancer cells' invasion in vitro and liver metastasis in
      vivo. These findings indicated that high USP6 expression contributed to the
      progression of colon cancer and USP6 may be a valuable prognostic factor in
      patients with colon cancer.

PMID- 30297113
TI  - The expected cumulative incidence of live birth of patients starting IVF
      treatment at age 41 years or older.
AB  - RESEARCH QUESTION: What is the cumulative incidence of live birth (CLIB) for high
      order consecutive IVF cycles, and which factors are associated with live birth of
      women aged >=41 years using autologous oocytes? DESIGN: A retrospective cohort
      study including 146 patients aged 41 years to <44 years who started their first
      IVF cycle attempt using autologous oocytes, between January 2006 and December
      2013. RESULTS: After 13 IVF cycles, CILB reached up to 33.6%. After six IVF
      cycles, 42 (28.8%) women delivered a live infant (85.7% of the total live birth).
      Mean live birth rate per cycle declined with age at the initial cycle (8% at 41
      years; 5.8% at 42 years; and 4.1% at 43 years). Multivariable modified Poisson
      regression models identified patient's age (RR for 41 years versus 43 years:
      0.47; 95% CI 0.25 to 0.87; P = 0.01), smoking status (RR 0.21; 95% CI 0.05 to
      0.08; P = 0.02), and mean number of fertilized oocytes (RR 1.23; 95% CI 1.08 to
      1.39; P < 0.01) as factors significantly associated with the probability of a
      live birth. CONCLUSIONS: Multiple repeat IVF cycles in women aged 41-44 years
      offers a reasonable long-term success rate. After six cycles of treatment, about
      29% of women of advanced reproductive age using autologous oocytes expected to
      achieve a live birth. This information might assist in fertility counselling and
      managing patients' expectations by adjusting the appropriate treatment strategy
      and number of IVF cycle attempts, especially in countries in which egg donation
      is prohibited or when multiple repeated IVF cycles attempts are financially
      affordable.

PMID- 30297114
TI  - Distinctive expression profiles of Caveolin-1 and Notch-1 protein in patients
      with nasal polyps or sinonasal inverted papillomas.
AB  - BACKGROUND: Nasal polyposis (NP) and sinonasal inverted papillomas (SIP) are
      considered benign lesions capable of recurrence or malignant transformation
      although not with the same prevalence. Since fluctuations of Caveolin-1 and Notch
      1 proteins expression have been reported in many pathologies, the current study
      aimed to investigate their involvement in the epithelial transformation observed
      in SIPs compared to NP. METHODS: Immunohistochemical expression of Caveolin-1 and
      Notch-1 proteins was assessed in 104 patients with sinonasal lesions (45 NP, 45
      SIP and 14 NP with SIP), semiquantively (percentage times intensity). Proteins
      expression profiles were evaluated statistically for their correlation with
      patients demographic and clinicopathological variables (grade of dysplasia,
      inflammation, recurrence) as well as with markers of proliferation (Ki67) and
      apoptosis (7-AAD) as determined by flow cytometry analysis. RESULTS: SIP lesions
      presented increased Caveolin-1 immunopositivity compared to NP (62.2%, vs 40.9%;
      p = 0.045). Cytoplasmic staining was observed only in epithelium's basal and
      suprabasal layers. Caveolin-1 positivity was not related to Ki67 expression,
      apoptosis, inflammation or dysplasia, eventhough 81.8% of highly immunopositive
      lesions were dysplastic (p = 0.03). Also, smokers presented significantly
      increased immunopositivy (p = 0.03). In contrast SIP lesions presented reduced
      Notch-1 expression compared to NP (68.9% vs 100%; p < 0.001). Dysplastic lesions
      presented low Notch-1 immunopositivity (p < 0.001). Enhancement of Notch-1 gene
      expression was also associated with inflammation. CONCLUSIONS: The herein
      presented data suggest that the expression profiles of Caveolin-1 and Notch-1
      proteins in sinonasal pathologies are distinctive and that could be explored as
      potential targets for the development of alternative therapeutic approaches.

PMID- 30297115
TI  - Are dual mobility cups associated with increased metal ions in the blood?
      Clinical study of nickel and chromium levels with 29 months' follow-up.
AB  - INTRODUCTION: Dual mobility cups have become the implant of choice for older
      patients with a high risk of dislocation. However, to our knowledge, no study has
      explored the possibility of metal ion production with these implants that
      incorporate a polyethylene-on-metal bearing. This led us to conduct a prospective
      study to determine whether use of a dual mobility cup is accompanied by increased
      levels of nickel and chromium in the blood. HYPOTHESIS: Use of a dual mobility
      cup is accompanied by an increase of nickel and chromium levels in the blood.
      METHODS: Between 2012 and 2015, 16 consecutive patients were enrolled in the
      study. They underwent primary hip arthroplasty with a ceramic BioloxTM head
      (CeramTec, Plochingen, Germany), CorailTM titanium alloy stem (DePuy Synthes,
      Saint Priest, France) and a NovaeTM dual mobility cup (SERF, Decines-Charpieu,
      France) consisting of 19% chromium (Cr) and 13-15% nickel (Ni). Patients who had
      other potential sources of nickel or chromium in their body (joint implants,
      dental implants, etc.) were excluded. The blood levels (MUg/L) of nickel and
      chromium were measured preoperatively and at 2 years' follow-up by an independent
      laboratory (Biomnis) using inductively coupled plasma mass spectrometry. The
      upper limits set by the laboratory were<0.87MUg/L for chromium and<1.0MUg/L for
      nickel. AP and lateral X-rays of the pelvis were taken preoperatively and at each
      postoperative follow-up visit to look for signs of loosening. The Postel-Merle
      d'Aubigne (PMA) score was determined preoperatively and at each postoperative
      follow-up visit. Surgical revision procedures for any cause were also documented.
      RESULTS: The mean follow-up was 29 months [13-39]. Preoperatively, blood nickel
      ion levels were measured in 7 patients; they were below 1MUg/L in 6 patients
      (86%) and at 1.5MUg/L in 1 patient (14%). The mean preoperative chromium ion
      levels (n=7) was 0.2MUg/L [0-0.8MUg/L]. Postoperatively, all 16 enrolled patients
      had their blood ion levels checked at a mean follow-up of 29 months. The nickel
      ion levels averaged 1.69+/-1.49 [0.2-5.6] (with 4/16 having>2MUg/L and
      12/16>1MUg/L) and the chromium ion levels averaged 0.5+/-0.11 [0.4-0.7] (with no
      patients>0.7MUg/L). There were no signs of loosening or osteolysis on the follow
      up radiographs. The mean PMA score at 2 years was 17.8 [17,18]. CONCLUSION: We
      found that dual mobility cups generate increased nickel but not chromium ions in
      the blood. The levels measured are comparable to those for other orthopedic
      implants such as spine implants. The clinical consequences of these increased
      levels are not known. Nevertheless, there were no clinical or radiological signs
      of loosening, although the follow-up was only 2 years. LEVEL OF EVIDENCE: IV,
      Cohort study.

PMID- 30297116
TI  - Acquired Urethrovaginal Fistula and Urethral Atresia in a Patient with a
      Sacrococcygeal Teratoma.
AB  - Acquired urethrovaginal fistulae and urethral atresia are rare findings in
      pediatric patients, but have been described in adult patients related to trauma
      or iatrogenic injury. Little exists in the published literature to guide
      management of such conditions in children, but lessons learned from congenital
      causes can help. Herein we discuss the preoperative evaluation and management of
      a child with an acquired urethrovaginal fistula and urethral atresia likely
      related to in utero compression from an intrapelvic sacrococcygeal teratoma and
      provide several images detailing the complex anatomy.

PMID- 30297117
TI  - .Clostridioides difficile.
AB  - Clostridioides difficile is a spore-forming, anaerobic, intestinal pathogen that
      causes severe diarrhea that can lead to death. In 2011, C. difficile infected
      ~500000 people in the USA and killed ~29000 people. C. difficile infection (CDI)
      is the most common healthcare-related infection in the USA, leading to increased
      healthcare costs of $4.8 billion. This pathogen transmits via the oral-fecal
      route as a highly contagious and resilient spore. Upon exposure to primary bile
      acids in the intestine, C. difficile germinates, and in the absence of
      colonization resistance from the normal microbiota, the bacterium colonizes the
      colon and produces toxins. These toxins inhibit actin polymerization in host
      cells, leading to cell death. C. difficile cells can then sporulate in the
      intestine and exit the body via diarrheal shedding. In culture, sporulation is
      induced at stationary phase in a nutrient-limiting environment, but the
      intestinal triggers of sporulation are still unknown.

PMID- 30297118
TI  - Sterically induced conformational restriction: Discovery and preclinical
      evaluation of novel pyrrolo[3,2-d]pyrimidines as microtubule targeting agents.
AB  - The discovery, synthesis and biological evaluations of a series of nine N5
      substituted-pyrrolo[3,2-d]pyrimidin-4-amines are reported. Novel compounds with
      microtubule depolymerizing activity were identified. Some of these compounds also
      circumvent clinically relevant drug resistance mechanisms (expression of P
      glycoprotein and betaIII tubulin). Compounds 4, 5, and 8-13 were one to two-digit
      nanomolar (IC50) inhibitors of cancer cells in culture. Contrary to recent
      reports (Banerjee et al. J. Med. Chem.2018, 61, 1704-1718), the conformation of
      the most active compounds determined by 1H NMR and molecular modeling are similar
      to that reported previously and in keeping with recently reported X-ray crystal
      structures. Compound 11, freely water soluble as the HCl salt, afforded
      statistically significant inhibition of tumor growth in three xenograft models
      [MDA-MB-435, MDA-MB-231 and NCI/ADR-RES] compared with controls. Compound 11 did
      not display indications of animal toxicity and is currently slated for further
      preclinical development.

PMID- 30297120
TI  - Chemistry-driven glycoscience.
AB  - Carbohydrates are the most prominent features of the cell's exterior-they are the
      cell's "face" and serve as the cell's identification card. The features of cell
      surface glycans (e.g. glycoproteins, glycolipids, polysaccharides) can be read by
      proteins, other cells, or organisms. In all of these contexts, glycan-binding
      proteins typically recognize ("read") glycan identity. This recognition mediates
      important host-microbe interactions, as well as critical physiological functions,
      including fertilization, development, and immune system function. This article
      focuses on how proteins recognize glycans with an emphasis on three objectives:
      1) to understand the molecular basis for carbohydrate recognition, 2) to
      implement that understanding to develop functional probes of protein-carbohydrate
      interactions, and 3) to apply those probes to elucidate and exploit the
      physiological consequences of protein-carbohydrate interactions. In this context,
      our group has focused on two key aspects of carbohydrate recognition: CH-pi and
      multivalent interactions. We are applying the foundational knowledge gained from
      our studies for purposes ranging from illuminating host-microbe interactions to
      probing immune system function.

PMID- 30297119
TI  - Discovery and biological evaluation of thiobarbituric derivatives as potent
      p300/CBP inhibitors.
AB  - Histone acetyltransferases (HATs) relieve transcriptional repression by
      preferentially acetylation of epsilon-amino group of lysine residues on histones.
      Dysregulation of HATs is strongly correlated with etiology of several diseases
      especially cancer, thus highlighting the utmost significance of the development
      of small molecule inhibitors against this potential therapeutic target. In the
      present study, through virtual screening and iterative optimization, we
      identified DCH36_06 as a bona fide, potent p300/CBP inhibitor. DCH36_06 mediated
      p300/CBP inhibition leading to hypoacetylation on H3K18 in leukemic cells. The
      suppression of p300/CBP activity retarded cell proliferation in several leukemic
      cell lines. In addition, DCH36_06 arrested cell cycle at G1 phase and induced
      apoptosis via activation of capase3, caspase9 and PARP that elucidated the
      molecular mechanism of its anti-proliferation activity. In transcriptome
      analysis, DCH36_06 altered downstream gene expression and apoptotic pathways
      related genes verified by real-time PCR. Importantly, DCH36_06 blocked the
      leukemic xenograft growth in mice supporting its potential for in vivo use that
      underlies the therapeutic potential for p300/CBP inhibitors in clinical
      translation. Taken together, our findings suggest that DCH36_06 may serve as a
      qualified chemical tool to decode the acetylome code and open up new
      opportunities for clinical intervention.

PMID- 30297121
TI  - Translating Evidence into Practice.

PMID- 30297122
TI  - Impact of maternally derived pertussis antibody titers on infant whole-cell
      pertussis vaccine response in a low income setting.
AB  - BACKGROUND: Maternal vaccines against pertussis are not yet recommended in the
      developing world. Besides unclear burden estimates, another concern is that
      transplacental transfer of maternal pertussis antibodies could result in
      attenuation of the immune response to whole cell pertussis (DTwP) primary
      vaccination series in infants. This study was taken up to determine whether
      higher levels of maternal pertussis antibodies attenuate immune response of
      infants to DTwP vaccination series given at 6-10-14 weeks of age. METHODOLOGY: A
      total of 261 pregnant women and their infants from four low-income settlements in
      Karachi, Pakistan were enrolled in this study. The study endpoints were infant
      antibody titers for Pertussis toxin (PTx), Filamentous hemagglutinin antigen
      (FHA), Pertactin (PRN) and Fimbriae type 2/3 (FIM) - from birth through 18 weeks
      of age. Cord blood or pre-vaccine pertussis antibody titers indicate the
      concentration of maternal antibodies transferred to infants. Linear regression
      models were used to determine the association between higher maternal antibody
      titers and infant immune response to DTwP vaccine. Geometric Mean Ratio (GMR) was
      calculated as the ratio of infant antibody titers at specified time points
      against the maternal antibody titers at the time of delivery. RESULTS: At
      eighteen weeks of age, the adjusted beta regression coefficient for PTx was 0.06
      (95% CI: -0.49-0.61), FHA 0.02 (95% CI: -0.26 -0.29), PRN 0.02 (95%CI -0.38-
      0.43), and FIM 0.17 (95%CI: -0.21-0.54). Among infants who received at least two
      doses of DTwP vaccine, higher maternal antibody titers did not have any
      attenuating effect on infant post-immunization antibody titers against all four
      pertussis antigens. CONCLUSION: Maternal pertussis antibodies did not attenuate
      infant's immune response to pertussis antigens in DTwP primary vaccine given at 6
      10-14 weeks of age.

PMID- 30297123
TI  - The roles of neighborhood composition and autism prevalence on vaccination
      exemption pockets: A population-wide study.
AB  - The number of children entering schools without mandated vaccinations has
      increased in high-income countries due to the rise of nonmedical exemptions from
      school vaccination requirements. Herd immunity is threatened when unvaccinated
      children are concentrated in spatial pockets. Despite the role of vaccine-autism
      controversy in the current wave of the anti-vaccine movement, we do not know if
      exemption clusters are associated with local autism rates; it is often assumed
      that these clusters are merely the result of sociodemographic composition. This
      study uses data on the number of students with a Personal Belief Exemption
      reported by schools from 1992 to 2014 and unique data on the locations of
      children with an autism diagnosis in California to study the correlates of large
      exemption pockets. Our spatial analysis shows that the prevalence of autism is
      not associated with the locations of large pockets of vaccination exemptions.
      Likewise, the spatial distributions of socioeconomic factors and proximity to
      health care resources have limited roles in explaining these large exemption
      pockets. Racial/ethnic composition, however, has strong associations with the
      locations of the large pockets. Our results suggest that community-level
      interventions are needed to maintain herd immunity as exemption pockets are not
      merely the result of population composition.

PMID- 30297125
TI  - Letter to prospective validation of the Parkland Grading Scale for Cholecystitis.

PMID- 30297124
TI  - Quadrivalent HPV vaccine in HIV-1-infected early adolescent girls and boys in
      Kenya: Month 7 and 12 post vaccine immunogenicity and correlation with immune
      status.
AB  - INTRODUCTION: In sub-Saharan Africa, a generation of HIV-1-infected children is
      approaching the age of sexual debut and becoming at risk for HPV infection and
      its sequelae. We assessed safety and immunogenicity of the quadrivalent HPV
      (qHPV) vaccine in HIV-1-infected adolescents. METHODS: In an open-label trial
      among Kenyan, HIV-1-infected adolescents aged 9-14 years, we administered the
      qHPV vaccine at 0, 2 and 6 months and measured antibody titers to HPV-16, 18, 6
      and 11 at month 7 and 12 post-vaccination. Measures of immunogenic response from
      HIV-1-negative historical cohorts from Africa and HIV-1 positive adolescent
      cohorts from the USA were used for comparison. RESULTS: We enrolled 100 girls and
      80 boys with a median age of 12 years and median baseline CD4 cell count of 684
      (IQR 478, 935) cells/uL. One hundred and fifty four (86%) were receiving
      antiretroviral therapy for a median of 4.5 (IQR 2.3, 6.3) years; 110 (71%) had
      <400 copies of plasma HIV-1 RNA/mL. Of 189 enrolled children, 179 received all
      three doses. Two hundred and eighty five (64%) of 445 adverse events were
      injection site reactions; none were greater than grade 2. Of 6 Serious Adverse
      Events (SAEs), none were considered vaccine related. Seroconversion to HPV-18,
      16, 11, 6 at month 7 occurred in 93.3%, 98.3%, 97.2% and 99.6% of vaccine
      recipients; similar rates have been reported in historical controls. The mean
      log10 HPV antibody titer measured at month 7 increased with each log10 increase
      in CD4 by 1.4 (95% CI: 1.1-1.7) for HPV-18; 1.2 (0.9-1.4) for HPV-16; 1.1 (0.8
      1.3) for HPV-11; 0.7 (0.5-1.0) for HPV-6 (all p < 0.0001). CONCLUSION: Almost all
      Kenyan HIV-1-infected adolescents mounted an immune response comparable to other
      immunized populations. HPV antibody titers were higher in those with preserved
      CD4 cell counts. Longer term-follow up will determine sustainability of the
      immune response. ClinicalTrials.gov number, NCT00557245.

PMID- 30297126
TI  - Applicant perceptions of new selection systems are a function of their
      performance in the selection procedure.
AB  - INTRODUCTION: Screening practices for selecting surgery trainees have been
      criticized for subjectivity, inefficiency, and inability to predict performance.
      This study explored applicant perceptions to an untraditional selection process.
      METHODS: Fellowship applicants completed an online assessment containing 26
      situational judgment test (SJT) items and a 108-item personality profile. High
      performing candidates participated in on-site structured interviews and skills
      testing. Upon completion of all interviews, but before match results were
      available, an anonymous, online survey was sent to all applicants. The survey
      asked about perceptions of the selection system along dimensions of procedural
      justice theory on a 1 (strongly disagree) to 5 (strongly agree) scale. RESULTS:
      Twenty-one of 51 applicants completed the survey. Those invited for an interview
      (N = 12) had more favorable perceptions about communication (3.50 +/- 1.38 versus
      2.00 +/- 0.82,p < 0.05), opportunity to perform (3.33 +/- 1.56 versus 1.29 +/-
      0.49,p < 0.01), fairness (4.50 +/- 0.80 versus 3.43 +/- 1.40,p < 0.05) and
      gaining more insight (4.25 +/- 1.22 versus 2.29 +/- 1.60,p < 0.01) compared to
      applicants not invited. Content (4.21 +/- 0.86) and consistency (4.79 +/- 0.42)
      means were similar. CONCLUSIONS: These results suggest that applicant perceptions
      are directly related to how well they perform in the selection procedure.

PMID- 30297127
TI  - Association of endogenous sex hormone levels with coronary artery calcium
      progression among post-menopausal women in the Multi-Ethnic Study of
      Atherosclerosis (MESA).
AB  - BACKGROUND: Sex differences in the incidence and manifestation of cardiovascular
      disease (CVD) suggest the involvement of sex hormones in disease pathogenesis.
      Coronary artery calcium (CAC) and its progression, measured by non-contrast
      cardiac computed tomography, are markers of subclinical atherosclerosis and
      predict CVD, even among low-risk women. We hypothesized that sex hormone levels
      were associated with CAC progression among women in the Multi-Ethnic Study of
      Atherosclerosis. METHODS: We studied 2759 post-menopausal women (age 65 +/- 9
      years), free of baseline CVD, with baseline serum sex hormones and CAC measured
      at Exam 1 (2000-2002). Of this sample, 2427 had >=1 follow-up CAC measurement
      through Exam 5 (2010-2012). Using mixed effects linear regression methods, we
      tested change in log[CAC+1] score by log[sex hormone] levels (continuous,
      comparing the 90th versus 10th percentiles). Models adjusted for demographics,
      lifestyle factors, cardiovascular risk factors, hormone therapy, and years since
      menopause. RESULTS: At baseline, we found no associations between sex hormones
      and prevalent CAC. Over a median of 4.7 years, in fully-adjusted models, women
      with higher free testosterone levels had relatively greater CAC progression
      [Ratio 1.26 (95% CI 1.01-1.56)], whereas higher sex hormone binding globulin
      (SHBG) was associated with lower progression risk [0.80 (0.64-0.99). No
      associations were seen for total testosterone, estradiol, or
      dehydroepiandrosterone. CONCLUSION: A more androgenic hormone profile of higher
      free testosterone and lower SHBG is associated with a greater CAC progression up
      to 10-years in post-menopausal women. Sex hormone levels may help identify women
      at increased risk for CVD who may benefit from additional risk-reducing
      strategies.

PMID- 30297129
TI  - Isolated aortic interruption complicated by type B aortic dissection: A rare case
      of "double trouble".

PMID- 30297128
TI  - Use of coronary artery calcium testing to improve coronary heart disease risk
      assessment in a lung cancer screening population: The Multi-Ethnic Study of
      Atherosclerosis (MESA).
AB  - BACKGROUND: Assessment of coronary artery calcium (CAC) during lung cancer
      screening chest computed tomography (CT) represents an opportunity to identify
      asymptomatic individuals at increased coronary heart disease (CHD) risk. We
      determined the improvement in CHD risk prediction associated with the addition of
      CAC testing in a population recommended for lung cancer screening. METHODS: We
      included 484 out of 6814 Multi-Ethnic Study of Atherosclerosis (MESA)
      participants without baseline cardiovascular disease who met U.S. Preventive
      Service Task Force CT lung cancer screening criteria and underwent gated CAC
      testing. 10 year-predicted CHD risks with and without CAC were calculated using a
      validated MESA-based risk model and categorized into low (<5%), intermediate (5%
      10%), and high (>=10%). The net reclassification improvement (NRI) and change in
      Harrell's C-statistic by adding CAC to the risk model were subsequently
      determined. RESULTS: Of 484 included participants (mean age = 65; 39% women; 32%
      black), 72 (15%) experienced CHD events over the course of follow-up (median =
      12.5 years). Adding CAC to the MESA CHD risk model resulted in 17% more
      participants classified into the highest or lowest risk categories and a NRI of
      0.26 (p = 0.001). The C-statistic improved from 0.538 to 0.611 (p = 0.01).
      CONCLUSIONS: CHD event rates were high in this lung cancer screening eligible
      population. These individuals represent a high-risk population who merit
      consideration for CHD prevention measures regardless of CAC score. Although
      overall discrimination remained poor with inclusion of CAC scores, determining
      whether those reclassified to an even higher risk would benefit from more
      aggressive preventive measures may be important.

PMID- 30297130
TI  - Effect of oral trazodone on the minimum alveolar concentration of isoflurane in
      dogs.
AB  - OBJECTIVE: To determine the effect of oral trazodone on the minimum alveolar
      concentration (MAC) of isoflurane in dogs. STUDY DESIGN: Prospective blinded,
      single-observer, randomized crossover experimental study. ANIMALS: Six adult (age
      6.8 +/- 1.6 months) healthy dogs (three males and three females), weighing 24.8
      +/- 3.4 kg (mean +/- standard deviation). METHODS: Each dog was anesthetized
      twice with a minimum of 7 days between anesthetic episodes. Dogs were randomly
      assigned to be administered two treatments in a crossover design: premedication
      with trazodone (8 mg kg-1; TRAZ-ISO) orally 2 hours prior to an anesthetic
      episode or no (ISO). Dogs were anesthetized with intravenous propofol (6 mg kg-1)
      and isoflurane in >95% oxygen. Isoflurane MAC was determined using an iterative
      bracketing technique with electrodes placed in the buccal mucosa. Hemodynamic
      variables were compared at the lowest end-tidal isoflurane concentration at which
      each dog did not respond. A paired t test was used to assess the effect of
      treatment on outcome variables with significance set to a value of p < 0.05.
      RESULTS: The MAC concentration (mean +/- standard deviation) in dogs administered
      TRAZ-ISO was 0.85 +/- 0.17% compared with 1.02 +/- 0.11% in those administered
      ISO (p = 0.01, 95% confidence interval -0.25 to -0.05), resulting in a mean MAC
      reduction of 17 +/- 12%. There were no differences in hemodynamic variables
      between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Premedication of dogs
      with oral trazodone (8 mg kg-1) 2 hours prior to anesthetic induction has a
      significant isoflurane MAC sparing effect with no significant observed
      hemodynamic benefit.

PMID- 30297131
TI  - Colon constipation in horses after sustained-release buprenorphine
      administration.
AB  - OBJECTIVE: To investigate the pharmacological profile and side effects of
      buprenorphine administered as a sustained-release formulation in horses. STUDY
      DESIGN: Pilot trial. ANIMALS: A total of four experimental horses, aged 18-27
      years and weighing 508-578 kg. METHODS: Buprenorphine (0.1 mg kg-1) was mixed as
      a freshly prepared sterile solution with a sustained-release drug carrier. It was
      administered by the subcutaneous (n = 2) or intramuscular (n = 2) route. During
      the experiment, the horses were closely monitored, equipped with a step counter
      and blood samples were collected for quantification of buprenorphine in plasma.
      RESULTS: All four horses developed colon constipation requiring medical therapy,
      together with increased locomotor activity. One horse, requiring surgical
      treatment of colon constipation, was euthanized during recovery from anaesthesia
      for weakness and severe lower airway obstruction. The three other horses
      recovered fully within 5-7 days. Plasma buprenorphine concentrations were between
      1 and 8 ng mL-1 for approximately 48 hours. No local reaction was observed at the
      injection sites. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of the
      sustained-release formulation of buprenorphine at a dose of 0.1 mg kg-1 resulted
      in plasma concentrations compatible with antinociceptive activity for at least 48
      hours. The observed severe and undesirable effects of colon constipation and
      increased locomotor activity definitely preclude clinical use of sustained
      release buprenorphine at this dose.

PMID- 30297132
TI  - A Plugin Framework for Extending the Simulation Capabilities of FEBio.
AB  - The FEBio software suite is a set of software tools for nonlinear finite element
      analysis in biomechanics and biophysics. FEBio employs mixture theory to account
      for the multiconstituent nature of biological materials, integrating the field
      equations for irreversible thermodynamics, solid mechanics, fluid mechanics, mass
      transport with reactive species, and electrokinetics. This communication
      describes the development and application of a new "plugin" framework for FEBio.
      Plugins are dynamically linked libraries that allow users to add new features and
      to couple FEBio with other domain-specific software applications without
      modifying the source code directly. The governing equations and simulation
      capabilities of FEBio are reviewed. The implementation, structure, use, and
      application of the plugin framework are detailed. Several example plugins are
      described in detail to illustrate how plugins enrich, extend, and leverage
      existing capabilities in FEBio, including applications to deformable image
      registration, constitutive modeling of biological tissues, coupling to an
      external software package that simulates angiogenesis using a discrete
      computational model, and a nonlinear reaction-diffusion solver. The plugin
      feature facilitates dissemination of new simulation methods, reproduction of
      published results, and coupling of FEBio with other domain-specific simulation
      approaches such as compartmental modeling, agent-based modeling, and rigid-body
      dynamics. We anticipate that the new plugin framework will greatly expand the
      range of applications for the FEBio software suite and thus its impact.

PMID- 30297133
TI  - Accurate In Silico Modeling of Asymmetric Bilayers Based on Biophysical
      Principles.
AB  - Technological advances in the last decade have enabled the study of ever more
      complex and physiologically relevant model membranes to help dispel the mystery
      surrounding the role of plasma membrane asymmetry in various cellular processes.
      The slowly accumulating body of experimental data is fueling renewed interest in
      and the need for computational methods to support interpretations and address a
      wide range of problems that are still not amenable to direct experimental study.
      The specific appeal of molecular dynamics simulations for this purpose lies in
      their ability to access information at atomic resolution, which is useful for the
      formulation of testable mechanistic hypotheses. But, the range of questions that
      can be addressed reliably with such simulations is determined by the appropriate
      construction and simulation of asymmetric bilayer models. One essential way to
      achieve this goal is to follow rigorous biophysical criteria and principles. In
      this context, we show that the requirement for a robust comparison between the
      properties of simulated asymmetric and symmetric model membranes is for the
      tension in each bilayer leaflet to be zero. Commonly used methods for
      constructing asymmetric bilayers, including matching the average areas of the
      leaflets from the corresponding symmetric systems, do not ensure zero leaflet
      tension, thus precluding physically realistic changes in the areas of the two
      leaflets. We present, to our knowledge, a new method for identifying the ideal
      lipid packing in bilayers with different leaflet compositions that achieves the
      zero-tension goal, and discuss the basic principles underlying the biophysically
      correct computational study of asymmetric membranes.

PMID- 30297134
TI  - Dynamic Migration Modes of Collective Cells.
AB  - Collective cell migration occurs in a diversity of physiological processes such
      as wound healing, cancer metastasis, and embryonic morphogenesis. In the
      collective context, cohesive cells may move as a translational solid, swirl as a
      fluid, or even rotate like a disk, with scales ranging from several to dozens of
      cells. In this work, an active vertex model is presented to explore the
      regulatory roles of social interactions of neighboring cells and environmental
      confinements in collective cell migration in a confluent monolayer. It is found
      that the competition between two kinds of intercellular social interactions-local
      alignment and contact inhibition of locomotion-drives the cells to self-organize
      into various dynamic coherent structures with a spatial correlation scale. The
      interplay between this intrinsic length scale and the external confinement
      dictates the migration modes of collective cells confined in a finite space. We
      also show that the local alignment-contact inhibition of locomotion coordination
      can induce giant density fluctuations in a confluent cell monolayer without gaps,
      which triggers the spontaneous breaking of orientational symmetry and leads to
      phase separation.

PMID- 30297136
TI  - Notions from Kavanaugh hearings contradict medical facts.

PMID- 30297135
TI  - Effect of an Intrinsically Disordered Plant Stress Protein on the Properties of
      Water.
AB  - Dehydrins are plant proteins that are able to protect plants from various forms
      of dehydrative stress such as drought, cold, and high salinity. Dehydrins can
      prevent enzymes from losing activity after freeze/thaw treatments. Previous
      studies had suggested that the dehydrins function by a molecular shield effect,
      essentially preventing a denatured enzyme from aggregating with another enzyme.
      Therefore, the larger the dehydrin, the larger the shield and theoretically the
      more effective the protection. Although this relationship holds for smaller
      dehydrins, it fails to explain why larger dehydrins are less efficient than would
      be predicted from their size. Using solvatochromic dyes to probe the solvent
      features of water, we first confirm that the dehydrins do not bind the dyes,
      which would interfere with interpretation of the data. We then show that the
      dehydrins have an effect on three solvent properties of water
      (dipolarity/polarizability, hydrogen-bond donor acidity and hydrogen-bond
      acceptor basicity), which can contribute to the protective mechanism of these
      proteins. Interpretation of these data suggests that although polyethylene glycol
      and dehydrins have similar protective effects, dehydrins may more efficiently
      modify the hydrogen-bonding ability of bulk water to prevent enzyme denaturation.
      This possibly explains why dehydrins recover slightly more enzyme activity than
      polyethylene glycol.

PMID- 30297137
TI  - Ebola virus epidemic in war-torn eastern DR Congo.

PMID- 30297138
TI  - Patients' experiences during the first 12 weeks after discharge in fast-track hip
      and knee arthroplasty - a qualitative study.
AB  - BACKGROUND: Due to the shortened length of stay in fast-track total hip and knee
      arthroplasty, patients must at a very early stage following surgery take
      responsibility for their postoperative care and treatment. It is important to
      establish if this treatment modality of fast-track is not only cost-effective,
      but meets patients' expectations and needs. AIM: To explore the lived experience
      of patients in fast-track total hip and knee arthroplasty during the first 12
      weeks after discharge. METHODS: A phenomenological-hermeneutic approach was used
      inspired by Ricoeur's theory of narrative and interpretation. Data were collected
      through semi-structured interviews with 8 patients 2 and 12 weeks after
      discharge. FINDINGS: Through the structural analysis 3 themes emerged: 1) Dealing
      with transition between hospital and home, 2) Pain and self-management of
      medication, 3) Challenges in rehabilitation. CONCLUSION: Patients appreciated
      only 1 or 2 days in hospital. However, they were not sufficiently involved in the
      discharge planning. There was a feeling of uncertainty and being left on their
      own after discharge, which could affect their pain management and recovery at
      home. There is a need to develop in partnership with each individual patient a
      post discharge plan of care and rehabilitation to meet their individual needs,
      preferences and mode of motivation.

PMID- 30297139
TI  - Radiology and Political Advocacy: Characterizing Radiology Political Action
      Committee Donors.
AB  - PURPOSE: To identify factors associated with radiologist donations to radiology
      political action committees (PACs). MATERIALS AND METHODS: A survey was emailed
      to 4474 radiologists. Factors investigated include demographics, donor history,
      and knowledge of the federal advocacy process. Logistic regression analysis was
      performed to determine factors associated with donor behavior. RESULTS: In total,
      336 radiologists completed the survey. Overall, 152 (46.2%) radiologists reported
      donating to a radiology PAC in the past year. Those with annual personal income
      >=$450,000 had greater odds to donate than those with annual personal income
      <$450,000 (odds ratio [OR]: 2.58, 95% confidence interval [CI]: 1.47-4.52; p <
      0.001). More than three-quarters (77.2%, n = 254) reported limited or no
      knowledge of the federal advocacy process. Those with good or excellent knowledge
      of the federal advocacy process had greater odds to donate than those with no
      knowledge (OR: 2.63, 95% CI: 1.01-6.84; p = 0.047). Those with awareness that
      membership dues and foundation funds do not fund Society of Interventional
      Radiology Political Action Committee had greater odds to donate (OR: 3.54, 95%
      CI: 2.00, 6.25; p < 0.001). CONCLUSIONS: Radiologists' personal income and
      knowledge of the federal advocacy process were identified as key factors
      influencing donations. PAC donation may benefit from raising awareness of the
      federal advocacy process, as well as from targeted fundraising strategies aimed
      at higher earners.

PMID- 30297140
TI  - Participant satisfaction with dementia prevention research: Results from Home
      Based Assessment trial.
AB  - INTRODUCTION: Little is known about factors affecting motivation and satisfaction
      of participants in dementia prevention trials. METHODS: A Research Satisfaction
      Survey was administered to 422 nondemented older adults who participated in the
      Home-Based Assessment trial. RESULTS: Overall satisfaction was high, with means
      of all individual items near to above a value of 3 on a scale from 1 (worst) to 4
      (best). Greater satisfaction was associated with staff-administered interviews
      versus automated technologies. The most liked aspects of research participation
      were volunteerism, opportunity to challenge and improve mental function, and
      positive interactions with staff. The least liked aspect was repetitiveness of
      the assessments. Participants requested more contact with staff and other older
      adults and more feedback on performance. DISCUSSION: Older adults' participation
      in research was primarily motivated by altruism. Methodologies that facilitate
      human contact, encourage feedback and novelty of tasks should be incorporated
      into future trial design.

PMID- 30297142
TI  - Delayed tension pneumocephalus following decompressive craniectomy.
AB  - Pneumocephalus is defined as a collection of air in the cranial cavity and is a
      common finding following intracranial neurosurgical procedures or following skull
      base fractures. The term tension pneumocephalus describes the accumulation of air
      under pressure such that it exerts mass effect and leads to a neurological
      deterioration. Whilst this is a rare event it can be life threatening and
      requires prompt intervention. We describe a case that occurred in a delayed
      fashion following a decompressive craniectomy for a severe traumatic brain
      injury. It was initially treated by urgent aspiration at a peripheral hospital
      under neurosurgical guidance.

PMID- 30297141
TI  - Levels of 4EBP1/eIF4E Activation in Renal Cell Carcinoma Could Differentially
      Predict Its Early and Late Recurrence.
AB  - BACKGROUND: The objective was to explore the predictive markers of late
      recurrence (LR) > 5 years after curative nephrectomy for renal cell carcinoma
      (RCC). PATIENTS AND METHODS: We retrospectively examined the data from 303
      patients with localized clear cell RCC treated surgically at our institution from
      1993 to 2011. Activation of the eukaryotic initiation factor (eIF)4E-binding
      protein 1 (4EBP1)/eIF4E axis at the mammalian target of rapamycin complex 1
      (mTORC1) was evaluated in the tumor specimens. Weak, intermediate, and strong
      immunohistochemistry staining grades were defined for 4EBP1, phosphorylated
      4EBP1, and eIF4E. The effects of clinicopathologic factors and activation level
      grades on tumor recurrence were analyzed using multivariate Cox regression
      models. To validate the present findings, we investigated clinical data from The
      Cancer Genome Atlas and protein/phosphoprotein data from corresponding patients
      from The Cancer Proteome Atlas. RESULTS: Of the 303 patients, 31 and 16 patients
      developed early recurrence (ER, <= 5 years) and LR, respectively. The activation
      levels were comparable among the subcategories of pathologic TN stage, Fuhrman
      grade, and microvascular and capsular invasion. Pathologic stage >= T1b, Fuhrman
      grade 3/4, and an intermediate or strong activation level correlated
      significantly with overall recurrence and ER. Strong activation of the axis and
      pathologic stage >= T1b were identified as independent predictors of LR. Only 2
      patients with weak activation experienced recurrence (1 each with ER and LR).
      Similar results were confirmed by the analyses of The Cancer Genome Atlas and The
      Cancer Proteome Atlas data. CONCLUSION: The activation level of the axis in RCC
      tissues could independently predict for recurrence and differentially affect the
      timing of recurrence.

PMID- 30297143
TI  - A tax on weight loss products based on fiction, not facts.
AB  - The recent article by Austin et al., "Could a tax on unhealthy products sold for
      weight loss reduce consumer use? A novel estimation of potential taxation
      effects," is disappointing for its lack of objectivity and its misrepresentation.
      While the conclusion is not surprising, the misinformation woven into the
      narrative is. Ultimately, their tax solution drives up cost; fails to distinguish
      between those willing to pay higher prices and those who are not; and may have
      relatively little influence on overall purchasing behavior.

PMID- 30297145
TI  - In situ administration of cytokine combinations induces tumor regression in mice.
AB  - BACKGROUND: Recent advances in cancer immunotherapy suggest a possibility of
      harnessing the immune system to defeat malignant tumors, but the complex
      immunosuppressive microenvironment confines the therapeutic benefits to a
      minority of patients with solid tumors. METHODS: A lentivector-based inducible
      system was established to evaluate the therapeutic effect of cytokines in
      established tumors. Intratumoral injection of certain cytokine combination in
      syngeneic tumor models was conducted to assess the therapeutic potentials.
      FINDINGS: Doxycycline (Dox)-induced local expression of cytokine combinations
      exhibites a strong synergistic effect, leading to complete regression of tumors.
      Notably, IL12 + GMCSF+IL2 expression induces eradication of tumors in all mice
      tolerated with this treatment, including those bearing large tumors of ~15 mm in
      diameter, and generates intensive systemic antitumor immunity. Other combinations
      with similar immune regulatory roles also induce tumor elimination in most of
      mice. Moreover, intratumoral injection of chitosan/IL12 + GMCSF+IL2 solution
      induces a complete response in all the tested syngeneic tumor models, regardless
      of various tumor immunograms. INTERPRETATION: Administration of certain cytokine
      combinations in tumor microenvironment induces a strong synergistic antitumor
      response, including the recruitment of large amount of immune cells and the
      generation of systemic antitumor immunity. It provides a versatile method for the
      immunotherapy of intractable malignant neoplasms. FUND: There is no external
      funding supporting this study.

PMID- 30297144
TI  - TRPA1 inhibition ameliorates pressure overload-induced cardiac hypertrophy and
      fibrosis in mice.
AB  - BACKGROUND: Recent evidence has indicated that the transient receptor potential
      ankyrin 1 (TRPA1) is expressed in the cardiovascular system and implicated in the
      development and progression of several cardiovascular diseases. However, the
      effects of TRPA1 on cardiac hypertrophy development remain unclear. The aim of
      this study was to determine the role of TRPA1 in cardiac hypertrophy and fibrosis
      development. METHODS: C57BL/6J mice were subjected to transverse aortic
      constriction (TAC) and were orally treated with the TRPA1 selective inhibitors HC
      030031 (HC) and TCS-5861528 (TCS). Morphological assessments, echocardiographic
      parameters, histological analyses and flow cytometry were used to evaluate
      cardiac hypertrophy and fibrosis. RESULTS: Human and mouse hypertrophic hearts
      presented with noticeably increased TRPA1 protein levels. Inhibition of TRPA1 by
      HC and TCS attenuated cardiac hypertrophy and preserved cardiac function after
      chronic pressure overload, as evidenced by increased heart weight/body weight
      ratio, cardiomyocyte cross-sectional area and mRNA expression of hypertrophic
      markers, including ANP, BNP and beta-MHC. Dramatic interstitial fibrosis was
      observed in the mice subjected to TAC surgery, and this was markedly attenuated
      in the HC and TCS treated mice. Mechanistically, the results revealed that TRPA1
      inhibition ameliorated pressure overload-induced cardiac hypertrophy by
      negatively regulating Ca2+/calmodulin-dependent protein kinase II (CaMKII) and
      calcineurin signaling pathways. We also demonstrated that blocking TRPA1
      decreased the proportion of M2 macrophages and reduced profibrotic cytokine
      levels, thereby improving cardiac fibrosis. CONCLUSIONS: TRPA1 inhibition
      protected against cardiac hypertrophy and suppressed cardiac dysfunction via Ca2+
      dependent signal pathways and inhibition of the M2 macrophages transition. These
      results suggest that TRPA1 may represent a potential therapeutic drug target for
      cardiac hypertrophy and fibrosis.

PMID- 30297146
TI  - Rhomboids and regulation of receptor tyrosine kinase ligands shedding.

PMID- 30297147
TI  - Urinary phthalate metabolites and metabolic syndrome in U.S. adolescents: Cross
      sectional results from the National Health and Nutrition Examination Survey (2003
      2014) data.
AB  - OBJECTIVE: There is limited research on the association between phthalates and
      metabolic syndrome (MetS). Among adolescents, phthalate exposure, which can occur
      from multiple sources, has been linked to several risk factors for MetS. The
      objective was to investigate the association between urinary phthalate metabolite
      concentrations (i.e., mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP),
      mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), mono-(3
      carboxylpropyl) phthalate (MCPP), and di(2-ethylhexyl phthalate (DEHP)) and MetS
      in adolescents aged 12-19 years using the National Health and Nutrition
      Examination Survey (NHANES) data (2003-2014). A secondary aim was to assess if
      observed associations varied by a measure of socioeconomic status, economic
      adversity, which was defined using parental income and educational attainment as
      well as household food security. METHODS: We used NHANES data which included
      physical examination, laboratory urinalysis and fasting blood profiles, and self
      reported health characteristics and demographics. Physical examination and
      laboratory data were used to obtain values of MetS components and urinary
      phthalate metabolites. We created age-, sex-, and survey year-specific tertiles
      of creatinine-corrected urinary phthalate metabolites. Analysis was performed
      using appropriate weighting procedures that accounted for NHANES' complex
      sampling design. After univariate and bivariate analyses, we performed adjusted
      logistic regressions to test for associations between individual phthalate
      metabolites and MetS as well as MetS components and number of MetS components,
      separately, using the lowest tertile as the reference category. A cross-product
      term (phthalate metabolite*economic adversity) was subsequently added to adjusted
      models. RESULTS: Among 918 participants (mean age 16 years, 45% female, 18% with
      economic adversity), the prevalence of MetS was 5.3%. Prior to adjustment,
      adolescents with MetS had marginally higher concentrations of phthalate
      metabolites than adolescents without MetS. There was a suggestive positive
      association between intermediate concentrations of MnBP and odds of MetS after
      adjustment (T2: Odds Ratio (OR) = 2.66 (95% confidence interval: 0.98-7.24); T3:
      OR = 2.11 (0.71-6.27)). Males with higher MnBP concentrations had higher odds of
      dyslipidemia; however, associations were mostly non-significant for females.
      Relationships between MiBP concentrations and odds of MetS varied by sex. Males
      with higher concentrations of MnBP and MiBP had greater odds of having a higher
      number of MetS components. Relationships between phthalate metabolites and MetS
      did not vary by economic adversity. CONCLUSION: There was a suggestive positive
      association between MnBP and MetS among adolescents. Associations between
      phthalate metabolites and MetS as well as MetS components may vary by sex, but
      may not vary by economic adversity. Further research of the relationships between
      phthalate exposures, MetS, and potential interactions with socioeconomic factors
      is warranted.

PMID- 30297148
TI  - Exploring nurses' end-of-life care for dying patients in the ICU using focus
      group interviews.
AB  - PURPOSE: The aim of this study is to illuminate how nurses working in an
      intensive care unit perceive their professional duties regarding end-of-life care
      based on their end-of-life care experience. DESIGN AND METHODS: A qualitative
      research design utilising focus-group interviews was employed. Two focus groups
      with twelve nurses were recruited, one consisting of nurses with less than five
      years of clinical experience in intensive care units and the other with more than
      five years of experience. FINDINGS: An analysis of the nurses' explorations of
      end-of-life care in an intensive care unit for patients facing impending death
      revealed three main themes: (1) facing an extreme change in human existence, (2)
      being in the presence of the patient's transition and (3) being prepared as an
      intensive care unit nurse. These three themes covered a total of 16 subthemes.
      CONCLUSION: The findings of this study outline how intensive care unit nurses
      perceive dying patients and how they manage end-of-life care. It also illustrates
      how patients and their families can be included in the process, and this should
      be a component of nurses' education regarding end-of-life care.

PMID- 30297149
TI  - Lived experiences of grief of Muslim nurses caring for patients who died in an
      intensive care unit: A phenomenological study.
AB  - OBJECTIVE: To describe the meaning of the lived experiences of grief of Muslim
      nurses caring for patients who died in an intensive care unit. METHODOLOGY:
      Gadamerian philosophy was used to underpin the hermeneutic phenomenological
      approach followed to analyse and interpret the lived experiences of nurses who
      cared for patients who died in intensive care units. Fourteen nurses met the
      inclusion criteria. They were asked to illustrate their experiences of grief
      using graphic representation. This was followed by face-to-face interviews during
      which they were asked to narrate and reflect on their experience. The graphic
      representation and interview transcripts were analysed using Van Manen's
      approach. Lincoln and Guba's criteria were followed to establish trustworthiness.
      SETTING: An intensive care unit at a tertiary public hospital in West Sumatra
      Province, Indonesia. FINDINGS: Five major thematic categories reflecting the five
      life-worlds were identified: 'empathetic understanding', 'balancing self',
      'avoidance', 'anticipating the future of own death', and 'relating technologies
      in bargaining'. CONCLUSION: This study provides further understanding of the
      meanings of the lived experience of grief among Muslim nurses in intensive care
      units. Nurses' grief arising from the loss of patients can affect their
      emotional, cognitive, spiritual, relational and professional well-being. The
      findings add further knowledge about the end of life in intensive care units.

PMID- 30297150
TI  - A multicase study of prolonged critical illness in the intensive care unit:
      Families' experiences.
AB  - BACKGROUND: It is widely acknowledged a critical illness is a stressful life
      event for not only the patient but also their family members; when an illness
      becomes prolonged, the impact is profound. It is suggested that as medical
      technologies advance, the number of days patients stay in an intensive care unit
      will increase. Therefore, it is important nurses understand how families
      experience a prolonged critical illness of their family member in an intensive
      care unit. OBJECTIVE: To explore the trajectory of a prolonged critical illness
      in the intensive care unit from the experiences of family. METHODS: A
      qualitative, longitudinal, multi-case design consisting of six cases from New
      Zealand intensive care units. Findings presented in this article only relate to
      the family's experiences, although patients and healthcare professionals formed
      part of each case. Data collection methods included observation, conversations,
      interviews and document review. Analysis was undertaken using thematic analysis,
      vignette development and trajectory mapping. FINDINGS: Relentless uncertainty
      dominated all phases of the trajectory for the family during a family member's
      prolonged critical illness in the intensive care unit. When faced with a critical
      illness, family shifted rapidly into a world of unknowns. Family worked hard to
      navigate their way through the many uncertainties that dominated each phase of
      their family member's illness. CONCLUSIONS: Nurses need to understand the levels
      of uncertainty families endure in order to provide care that meets the
      philosophical underpinnings of family centred care.

PMID- 30297151
TI  - Intensive care nurses fail to translate knowledge and skills into practice - A
      mixed-methods study on perceptions of oral care.
AB  - OBJECTIVES: To identify intensive care nurses' perceptions of oral care according
      to Coker et al.'s (2013) conceptual framework and to contribute to the knowledge
      base of oral care in intensive care. DESIGN/METHODS: This was a concurrent
      embedded mixed-methods design, with more weight given to the quantitative part.
      Participants responded to the Nursing Care related to Oral Health questionnaire,
      including perceptions of oral care antecedents (18 items), defining attributes
      (17 items), and consequences (6 items) and two open-ended questions. The data
      were analysed with descriptive and correlation statistics and qualitative content
      analysis. SETTING: Intensive care nurses (n = 88) in six general intensive care
      units. RESULTS: Intensive care nurses perceived that an important part of nursing
      care was oral care, especially to intubated patients. They perceived that the
      nursing staff was competent in oral care skills and had access to different kinds
      of equipment and supplies to provide oral care. The oral cavity was inspected on
      a daily basis, mostly without the use of any assessment instruments. Oral care
      seemed to be task-oriented, and documentation of the patients' experiences of the
      oral care process was rare. CONCLUSIONS: The antecedents, knowledge and skills
      are available to provide quality oral care, but intensive care nurses seem to
      have difficulties translating these components into practice. Thus they might
      have to shift their task-oriented approach towards oral care to a more person
      centred approach in order to be able to meet patients' needs.

PMID- 30297152
TI  - [Occupational and non occupational exposure to viral risk].
AB  - The transmission of an infectious disease can occur through exposure to blood or
      other potentially infectious body fluids, particularly in the event of skin
      puncture injuries for healthcare workers, and during sexual intercourse. These
      situations are known as accidental blood exposures and sexual exposures
      respectively. Combined actions carried out have allowed to significantly reduce
      risks, either to healthcare professionals (by standard precautions, provision of
      safety devices, Hepatitis B vaccination made compulsory in the 1990s,
      antiretroviral post-exposure prophylaxis that should be initiated as soon as
      possible after exposure), or to people engaging in unprotected sex (by prevention
      messages, condom promotion, and antiretroviral post-exposure prophylaxis). In any
      case, treatment of people infected by chronic diseases such as HBV or HIV, as
      well as possible drug eradication of HCV, are key for decreasing post-exposure
      risk of disease transmission. Post-exposure prophylaxis should be initiated as
      early as possible and intended for use only in patients with high-risk exposures.
      Knowledge of source person serostatus, information of exposed person on
      prevention, benefits and risks of treatment, and follow-up procedure are key
      points. Procedures to be followed in the event of an exposure must be known by
      all. Arrangements set up to allow risk assessment and management of exposed
      people rely on hospital services operating on a permanent basis.

PMID- 30297153
TI  - The Thermodynamics of Development in Bioartificial Tissue Design.
AB  - The fabrication of bioartificial tissues with authentic structures that could
      assure their clinical efficacy remains a challenging problem. A new paradigm has
      emerged that designs bioartificial tissues as intermediate in development tissue
      forms, which can inherently progress autonomously on developmental pathways, self
      organizing their cells into tissue structures as in their in vivo development.
      Biological processes involved in energy exchange between co-developing tissues
      are responsible for cell organization into the thermodynamically robust cellular
      patterns of tissue structures. Bioartificial tissue design rules that aim towards
      in vitro recapitulation of these processes can ensure the thermodynamic operation
      of developing tissues, leading to formation of the cellular patterns of tissue
      structures.

PMID- 30297154
TI  - Evolution of the National Institute of Nursing Research Logic Model for Center
      Sustainability.
AB  - BACKGROUND: Logic models are tools to evaluate the effectiveness of programs. In
      2013, the National Institute of Nursing Research (NINR) Logic Model for Center
      Sustainability was developed. PURPOSE: The purpose of this paper is to describe
      the process of revision and implementation of the NINR Logic Model across a
      continuum of NINR Exploratory Centers and Centers of Excellence. METHODS: The
      process for incorporating common data elements for symptom, self-management,
      biomarker science and precision health in the logic model is outlined.
      Information about the NINR Logic Model was gleaned from the National Institutes
      of Health Reporter, annual NINR Center Directors meetings, and from individual
      Center Directors. DISCUSSION: Centers utilized the model for funding applications
      and to guide Core administration, evaluation, Center sustainability, and/or other
      Center metrics. CONCLUSIONS: The revised NINR Logic Model for Center
      Sustainability can be a useful tool for planning and implementing center
      activities for center impact and sustainability.

PMID- 30297155
TI  - Influence of Graft Source on Postoperative Activity and Joint Laxity in Posterior
      Cruciate Ligament Reconstruction: A Systematic Review.
AB  - PURPOSE: To compare the clinical and functional outcomes of allograft and
      autograft reconstruction in patients with posterior cruciate ligament (PCL)
      deficiency. METHODS: The MEDLINE, Embase, and Cochrane Library databases were
      used to identify all relevant articles. Clinical outcomes including International
      Knee Documentation Committee, Tegner, and Lysholm scores; joint laxity; and
      posterior tibial displacement were evaluated. RESULTS: Among the 145 unique
      articles identified during the title screening, 25 studies published between 2002
      and 2016 with a combined population of 900 patients were deemed eligible for
      inclusion in the review. Of the 900 patients, 603 were treated with autograft and
      297 were treated with allograft PCL reconstruction. Five of the included studies
      directly compared autograft and allograft PCL reconstruction. Most studies found
      postoperative functional outcomes and joint laxity to improve postoperatively
      regardless of graft source. With only 1 exception, the included comparative
      studies found no significant postoperative difference in any of the functional
      outcome scores between patients treated with allograft and those treated with
      autograft. Two comparative studies found autograft reconstruction to result in
      significantly less posterior laxity than in the allograft group, whereas 2
      comparative studies found no significant difference in posterior laxity between
      the 2 groups. CONCLUSIONS: PCL reconstruction results in improved functional
      outcome scores and joint laxity regardless of graft source. Current studies
      suggest there is no significant difference in postoperative functional outcomes
      between patients treated with autograft and those treated with allograft.
      Patients treated with autograft have donor-site morbidity that is not associated
      with allograft reconstruction. Some evidence suggests that autograft
      reconstruction may result in reduced posterior laxity relative to allograft
      reconstruction. The magnitude of this finding, however, may not be clinically
      significant. Our review found that decision making based on the current
      literature is at high risk of potential bias. LEVEL OF EVIDENCE: Level IV,
      systematic review of Level I to IV studies.

PMID- 30297156
TI  - Outcomes After Arthroscopic Rotator Interval Closure for Shoulder Instability: A
      Systematic Review.
AB  - PURPOSE: (1) To systematically assess the clinical outcomes of arthroscopic
      rotator interval closure (RIC) procedures for shoulder instability and (2) to
      report the different technical descriptions and surgical indications for this
      procedure. METHODS: Two independent reviewers searched 4 databases (PubMed,
      Embase, Web of Science, and Cochrane) from database inception until October 15,
      2017. The inclusion criteria were studies that reported outcomes of shoulder
      stabilization using arthroscopic RIC as an isolated or adjunctive surgical
      procedure. The methodologic quality of studies was assessed with the
      Methodological Index for Non-Randomized Studies tool and Grading of
      Recommendations Assessment, Development and Evaluation system for randomized
      controlled trials. RESULTS: Fifteen studies met our search criteria (524
      patients). Of the studies, 12 were graded Level IV evidence; 2, Level III; and 1,
      Level II. Six different RIC technique descriptions were reported, with 2 studies
      not defining the details of the procedure. The most common method of RIC was
      arthroscopic plication of the superior glenohumeral ligament to the middle
      glenohumeral ligament (8 of 15 studies). The most commonly used patient-reported
      outcome measure was the Rowe score, with all studies reporting a minimum
      postoperative score of 80 points. The rate of return to preinjury level of sport
      ranged from 22% to 100%, and the postoperative redislocation rate ranged from 0%
      to 16%. CONCLUSIONS: The indications for RIC were poorly reported, and the
      surgical techniques were inconsistent. Although most studies reported positive
      clinical results, the heterogeneity of outcome measures limited our ability to
      make definitive statements about which types of rotator interval capsular closure
      are warranted for select subgroups undergoing arthroscopic shoulder
      stabilization. LEVEL OF EVIDENCE: Level IV, systematic review of Level II through
      IV studies.

PMID- 30297157
TI  - A blooming and buzzing confusion: Buffon, Reimarus, and Kant on animal cognition.
AB  - Kant's views on animals have received much attention in recent years. According
      to some, Kant attributed the capacity for objective perceptual awareness to non
      human animals, even though he denied that they have concepts. This position is
      difficult to square with a conceptualist reading of Kant, according to which
      objective perceptual awareness requires concepts. Others take Kant's views on
      animals to imply that the mental life of animals is a blooming, buzzing
      confusion. In this article I provide a historical reconstruction of Kant's views
      on animals, relating them to eighteenth-century debates on animal cognition. I
      reconstruct the views of Buffon and Reimarus and show that (i) both Buffon and
      Reimarus adopted a conceptualist position, according to which concepts structure
      the cognitive experience of adult humans, and (ii) that both described the mental
      life of animals as a blooming, buzzing confusion. Kant's position, I argue, is
      virtually identical to that of Reimarus. Hence Kant's views on animals support a
      conceptualist reading of Kant. The article further articulates the historical
      antecedents of the Kantian idea that concepts structure human cognitive
      experience and provides a novel account of how the ideas of similarity and
      difference were conceptualized in eighteenth-century debates on animal cognition.

PMID- 30297158
TI  - Advancing research on blood coagulation and thrombosis: Reply to the comments on
      "Modeling thrombosis in silico: Frontiers, challenges, unresolved problems and
      milestones".

PMID- 30297160
TI  - Homeless crack cocaine users: Territories and territorialities in the
      constitution of social support networks for health.
AB  - Homeless crack users are an important segment of the population living in extreme
      vulnerability in Brazil. In 2011, the Consultorio na Rua - CnaR (Street Clinic)
      was created, to improve access to health care for this population. Considering
      building up social support networks as a strategy to face life's difficulties,
      this study aims to analyse how crack users, in Rio de Janeiro, relate to
      territory and build social support networks to deal with their everyday life
      challenges and health needs. We carried out in-depth interviews with 10 homeless
      crack users assisted by CnaR and 11 health professionals; one Focus Group with 6
      users, and Participant Observation of CnaR's work during 2014-2016. Methodology
      was based on the use of an analytical matrix with theoretical and empirical
      categories of "Territory", "Territoriality", "Social Support Networks" and
      "Gift". Results revealed crack users' territorialities, alternating moments of
      concentration and disaggregation with high geographical mobility, except in
      periods of strong consumption of crack. Territorialities are unstable, marked by
      violent Police repression. In spite of the stories of losses and ruptures, forms
      of sociability among users and CnaR professionals were identified, as well as
      with different actors in the territory. All this favoured the formation of
      supportive networks providing friendship, health care, and other material and
      symbolic goods. The systematization of the users' informal networks, usually
      invisible to workers and administrators, is relevant because of its potential to
      expand the production of care and strengthen the associations in the territory.
      To understand users' territorialities and the social support networks formed in
      their everyday life is not only innovative, but also contributes to the
      formulation of public policies that aim to guarantee civil rights to people in a
      situation of vulnerability, suffering and social exclusion.

PMID- 30297161
TI  - Mechanistic philosophies of development: Theodor Boveri and Eric H. Davidson.

PMID- 30297159
TI  - ARID3a gene profiles are strongly associated with human interferon alpha
      production.
AB  - Type I interferons (IFN) causes inflammatory responses to pathogens, and can be
      elevated in autoimmune diseases such as systemic lupus erythematosus (SLE). We
      previously reported unexpected associations of increased numbers of B lymphocytes
      expressing the DNA-binding protein ARID3a with both IFN alpha (IFNalpha)
      expression and increased disease activity in SLE. Here, we determined that
      IFNalpha producing low density neutrophils (LDNs) and plasmacytoid dendritic
      cells (pDCs) from SLE patients exhibit strong associations between ARID3a protein
      expression and IFNalpha production. Moreover, SLE disease activity indices
      correlate most strongly with percentages of ARID3a+ LDNs, but were also
      associated, less significantly, with IFNalpha expression in LDNs and pDCs.
      Hierarchical clustering and transcriptome analyses of LDNs and pDCs revealed SLE
      patients with low ARID3a expression cluster with healthy controls and identified
      gene profiles associated with increased proportions of ARID3a- and IFNalpha
      expressing cells of each type. These data identify ARID3a as a potential
      transcription regulator of IFNalpha-related inflammatory responses and other
      pathways important for SLE disease activity.

PMID- 30297162
TI  - In Cocaine Dependence, Neural Prediction Errors During Loss Avoidance Are
      Increased With Cocaine Deprivation and Predict Drug Use.
AB  - BACKGROUND: In substance-dependent individuals, drug deprivation and drug use
      trigger divergent behavioral responses to environmental cues. These divergent
      responses are consonant with data showing that short- and long-term adaptations
      in dopamine signaling are similarly sensitive to state of drug use. The
      literature suggests a drug state-dependent role of learning in maintaining
      substance use; evidence linking dopamine to both reinforcement learning and
      addiction provides a framework to test this possibility. METHODS: In a randomized
      crossover design, 22 participants with current cocaine use disorder completed a
      probabilistic loss-learning task during functional magnetic resonance imaging
      while on and off cocaine (44 sessions). Another 54 participants without Axis I
      psychopathology served as a secondary reference group. Within-drug state and
      paired-subjects' learning effects were assessed with computational model-derived
      individual learning parameters. Model-based neuroimaging analyses evaluated
      effects of drug use state on neural learning signals. Relationships among model
      derived behavioral learning rates (alpha+, alpha-), neural prediction error
      signals (delta+, delta-), cocaine use, and desire to use were assessed. RESULTS:
      During cocaine deprivation, cocaine-dependent individuals exhibited heightened
      positive learning rates (alpha+), heightened neural positive prediction error
      (delta+) responses, and heightened association of alpha+ with neural delta+
      responses. The deprivation-enhanced neural learning signals were specific to
      successful loss avoidance, comparable to participants without psychiatric
      conditions, and mediated a relationship between chronicity of drug use and desire
      to use cocaine. CONCLUSIONS: Neurocomputational learning signals are sensitive to
      drug use status and suggest that heightened reinforcement by successful avoidance
      of negative outcomes may contribute to drug seeking during deprivation. More
      generally, attention to drug use state is important for delineating substrates of
      addiction.

PMID- 30297163
TI  - Indirect adjustment of relative risks of an exposure with multiple categories for
      an unmeasured confounder.
AB  - PURPOSE: With observational epidemiologic studies, there is often concern that an
      unmeasured variable might confound an observed association. Investigators can
      assess the impact from such unmeasured variables on an observed relative risk
      (RR) by utilizing externally sourced information and applying an indirect
      adjustment procedure, for example, the "Axelson adjustment." Although simple and
      easy to use, this approach applies to exposure and confounder variables that are
      binary. Other approaches eschew specific values and provide only bounds on the
      potential bias. METHODS: For both multiplicative and additive RR models, we
      present formulae for indirect adjustment of observed RRs for unmeasured potential
      confounding variables when there are multiple categories. In addition, we suggest
      an alternative strategy to identify the characteristics that the confounder must
      have to explain fully the observed association. RESULTS AND CONCLUSIONS: We
      provide examples involving studies of pediatric computer tomography scanning and
      leukemia and nuclear radiation workers and smoking to demonstrate that with
      externally sourced information, an investigator can assess whether confounding
      from unmeasured factors is likely to occur.

PMID- 30297164
TI  - Analysis of a National Programme for Selective Internal Radiation Therapy for
      Colorectal Cancer Liver Metastases.
AB  - AIMS: Patients with chemotherapy-refractory colorectal cancer liver metastases
      have limited therapeutic options. Selective internal radiation therapy (SIRT)
      delivers yttrium 90 microspheres as a minimally invasive procedure. This
      prospective, single-arm, observational, service-evaluation study was part of
      National Health Service England Commissioning through Evaluation. METHODS:
      Patients eligible for treatment had histologically confirmed carcinoma with liver
      only/liver-dominant metastases with clinical progression during or following
      oxaliplatin-based and irinotecan-based chemotherapy. All patients received SIRT
      plus standard of care. The primary outcome was overall survival; secondary
      outcomes included safety, progression-free survival (PFS) and liver-specific PFS
      (LPFS). RESULTS: Between December 2013 and March 2017, 399 patients were treated
      in 10 centres with a median follow-up of 14.3 months (95% confidence interval 9.2
      19.4). The median overall survival was 7.6 months (95% confidence interval 6.9
      8.3). The median PFS and LPFS were 3.0 months (95% confidence interval 2.8-3.1)
      and 3.7 months (95% confidence interval 3.2-4.3), respectively. During the follow
      up period, 143 patients experienced an adverse event and 8% of the events were
      grade 3. CONCLUSION: Survival estimates from this pragmatic study show clinical
      outcomes attainable in the National Health Service comparable with previously
      published data. This study shows the value of a registry-based commissioning
      model to aid national commissioning decisions for highly specialist cancer
      treatments.

PMID- 30297165
TI  - Patella tracking calculation from patellofemoral positions at finite angles of
      knee flexion.
AB  - Patellofemoral (PF) pain is a common knee disease. Patella tracking has a
      significant correlation with PF pain, therefore it could be used as an index for
      diagnosis and treatment evaluation. Previous research has proposed a method for
      measuring in vivo patella tracking by means of an interpolation algorithm. The
      present study aimed to quantify the effect of the interpolation parameters on the
      accuracy of the patella tracking with a motion capture experiment. The precise
      patella tracking of 5 knee specimens was collected and compared with the
      interpolated tracking. The results showed that the total interpolation error
      decreased to 2 mm with the number of interpolation angles increasing to 6. The
      number of interpolation reference points had a slight influence on the accuracy.
      The findings consolidated the feasibility of using interpolation to measure the
      in vivo patella tracking, and can help to optimize the accuracy and efficiency of
      the methodology.

PMID- 30297166
TI  - The implementation of the ballast water management convention in the Adriatic Sea
      through States' cooperation: The contribution of environmental law and
      institutions.
AB  - The Adriatic Sea, a semi-enclosed and vulnerable environment, deserves special
      attention regarding the risk of introducing Harmful Aquatic Organisms and
      Pathogens via ships' ballast water as new species findings occur at an alarming
      rate. This species introduction vector was addressed with the 2004 International
      Convention for the Control and Management of Ships' Ballast Water and Sediments,
      which entered into force in 2017. The efficient implementation of this convention
      calls for Adriatic States' cooperation on environmental specifics that have not
      been dealt with neither by national nor by international measures yet. Based on
      legal and institutional data gathered, and considering the regional maritime
      traffic and environmental specifics, this paper reveals that the integration of
      current environmental law commitments as well as a better dialogue between public
      institutions from shipping and environmental sectors may foster the
      implementation of ballast water management obligations through appropriate
      Adriatic States' cooperation.

PMID- 30297167
TI  - Handling of Missing Outcome Data in Acute Stroke Trials: Advantages of Multiple
      Imputation Using Baseline and Postbaseline Variables.
AB  - BACKGROUND: In acute stroke randomized trials, missingness of final functional
      outcome data reduces study power and potentially biases findings of treatment
      effect. Best methods for handling missing outcome data have not been well
      delineated for diseases with monophasic onset and subsequent improvement, like
      acute stroke. METHODS: We simulated data missingness in the public dataset of the
      landmark, second NINDS-tPA trial, by randomly removing 5%-25% of actual values
      for the 3-month modified Rankin Scale (mRS) of global disability. We evaluated 5
      missing data-handling methods: complete case analysis (CCA), worst case
      imputation (WCI), last observation carried forward (LOCF), multiple imputation
      using baseline covariates only (MI-B), and multiple imputation using baseline and
      postbaseline observations (MI-BP). RESULTS: With the original trial's 333
      patients, tissue plasminogen activator was associated with 3-month disability
      benefit, both for mRS dichotomized at 0-1 (P = .014) and shift analysis (P =
      .035). Distance (root mean square error) of imputed from actual mRS values was
      best for LOCF (1.17) and MI-BP (1.28), intermediate for MI-B (1.89) and worst for
      WCI (3.77). Directional bias (mean difference) was least for MI-BP (.01) and MI-B
      (-.16), intermediate for LOCF (-.37), and worst for WCI (-3.22). Preservation of
      formally positive results was greatest for MI-BP and LOCF (preserved at all
      missingness rates), intermediate for CCA and MI-B (preserved only with
      missingness <10%-20%), and least for WCI (preserved only with missingness <5%
      20%). CONCLUSIONS: For acute stroke trials, multiple imputation using baseline
      and postbaseline observations is an advantageous approach to missing outcome data
      handling, yielding high accuracy, reduced directional bias, and greater
      preservation of study power.

PMID- 30297168
TI  - History of Carotid Occlusions: The Contribution of Egas Moniz.
AB  - OBJECTIVE: To describe the first cases of carotid occlusions identified by the
      Portuguese neurologist Egas Moniz while performing the cerebral angiography he
      invented. METHODS: We reviewed the publications of Egas Moniz on the subject of
      cerebral angiography and ischemic stroke. RESULTS: We identified the first
      description of carotid occlusion a situation unknown until then. Also, some of
      the carotid occlusions he described were suggestive of dissection an unknown
      situation. Nevertheless, he admitted the role of trauma in such cases by
      lesioning the intimal layer and he also described the characteristic post-bulbar
      "bezel-like" image of dissection. CONCLUSIONS: In 1936 Egas Moniz described, for
      the first time, one case of carotid occlusion a situation unknown until then. He
      also described some of the characteristic aspects of carotid dissections. Carotid
      occlusions were only thoroughly described in English literature more than a
      decade later with the well-known work of Miller Fisher, in 1951.

PMID- 30297169
TI  - Epidemiology and Outcomes of Ischemic Stroke and Transient Ischemic Attack in the
      Adult and Geriatric Population.
AB  - BACKGROUND: Rate of ischemic strokes and transient ischemic attacks (TIAs)
      increases with age. There is lack of evidence on how age affects treatment
      strategies and outcomes. Our aim is to compare epidemiology of ischemic strokes
      and TIAs in adult and geriatric populations including risk factors, treatment
      delivered, and outcomes. DESIGN: We designed a retrospective cross-sectional
      review of patients admitted to neurology with diagnosis of stroke or TIA from
      2010 to 2015. Obtained variables were: age, sex, risk factors, acute therapy,
      National Institutes of Health Stroke Scale on admission and discharge, and
      disposition. Means, confidence intervals, or percentages were calculated as
      appropriate. RESULTS: Around 1,457 patients were divided into two groups: younger
      than 80 (n = 968) and 80 and older (n = 487). Rates of stroke and TIA were
      similar across younger and older groups (11% versus 12% TIA and 89% versus 88%
      stroke, respectively). Younger patients had lower admission National Institutes
      of Health Stroke Scale (mean 4.64 versus 7.84 in older group) and greater
      improvement on discharge (mean change -1.51 versus -1.29 accordingly). Older
      patients received tissue-type plasminogen activator (tPA) more often than younger
      patients, but no difference in rates of thrombectomy between groups. Older
      patients were more likely to have hypertension, atrial fibrillation, coronary
      artery disease, and less likely to be a smoker. On discharge, younger patients
      with stroke were discharged home or to acute rehab more frequently, regardless of
      tPA administration. CONCLUSIONS: Older patients had more comorbidities, received
      tPA more often, and had worse outcomes regardless of use of intravenous tPA or
      thrombectomy, and were more frequently institutionalized after discharge.

PMID- 30297170
TI  - Secular Trends in the Background of Intracerebral Hemorrhage from 2010 to 2015.
AB  - OBJECTIVE: Direct oral anticoagulants (DOACs) were recently introduced for the
      clinical use in stroke prevention, and they are reported to show a lower risk of
      intracerebral hemorrhage (ICH) compared to warfarin. We were interested to know
      whether there is any change in clinical backgrounds of ICH patients to date.
      METHODS: From 2010 to 2015, ICH patients admitted to our hospital were
      consecutively screened (n = 658). Hematoma size was assessed by brain computed
      tomography images on admission. Outcome was measured by the modified Rankin
      Scale, and favorable outcome was defined as modified Rankin Scale 0-2. Biennial
      trends were compared in 3 periods, P1: 2010-2011, P2: 2012-2013, and P3: 2014
      2015. RESULTS: The percentage of ICH patients taking antithrombotics had been
      slightly decreasing (P = .245: [P1] 33.0%, [P2] 27.4%, and [P3] 26.2%). The
      frequency of patients taking antiplatelets had significantly decreased (P = .001:
      [P1] 50.7%, [P2] 44.3%, and [P3] 22.8%), and those taking DOACs had significantly
      increased (P = .001: [P1] 1.4%, [P2] 4.9%, and [P3] 19.3%). Frequency of
      favorable outcomes in patients taking antithrombotics was slightly increased in
      P3 compared to P1 and P2 (23.3%, 21.1%, and 21.3%, respectively). There was no
      significant difference in hematoma size between patients taking warfarin and
      DOACs. CONCLUSIONS: Number of ICH patients taking antithrombotics has been
      slightly decreasing and the percentage taking DOACs among ICH has been increasing
      for 6years.

PMID- 30297171
TI  - Analysis of Availability and Access of Anti-myeloma Drugs and Impact on the
      Management of Multiple Myeloma in Latin American Countries.
AB  - INTRODUCTION: Latin American countries (LATAMC) represent a large fraction of
      patients treated for multiple myeloma (MM) worldwide. In order to understand the
      difficulty of access to anti-myeloma therapy in LATAMC, we designed this study
      that explores areas involved in the availability of drugs, such as health care
      systems, approval times, coverage of new agents, old drugs, use of generics, and
      the first-line treatments. MATERIAL AND METHODS: We collected data from 16
      countries in 2015. RESULTS: The majority of LATAMC (88%; n = 14) had mixed public
      and private coverage, with patients with MM cared for in public institutions.
      Although bortezomib and lenalidomide were approved in 100% and 73% in LATAMC,
      these figures did not translate to real-world practice as one-half of the nations
      reported unequal access to the new agents (thalidomide, bortezomib, and
      lenalidomide) in both public and private systems. Conversely, cheaper old drugs,
      represented by melphalan, were not available commercially in 44% (n = 7) of
      nations. Thus, first-line MM treatments for old and young patients in public
      practice were triplets with thalidomide-alkylating agent-steroid, whereas in
      private practice, treatments involved bortezomib-alkylating agent-steroid. An
      alarming rate of 30% of the nations reported suboptimal regimens (eg, VAD
      [vincristine, adriamycin, and dexamethasone]) or the impossibility of
      transplantation. CONCLUSION: Our data indicates that bortezomib and transplant
      are still an unmet medical necessity in public systems. In the complex puzzle of
      myeloma drug access in LATAMC, important issues, such as the adjustment of
      disparities between health systems, the incorporation of new drugs with an
      economic cost-effectiveness view, and the re-establishment of essential old
      drugs, can be a platform to the future.

PMID- 30297172
TI  - Smartphone-based differential pulse amperometry system for real-time monitoring
      of levodopa with carbon nanotubes and gold nanoparticles modified screen-printing
      electrodes.
AB  - Parkinson's disease caused by lack of dopamine in brain is a common
      neurodegenerative disorder. The traditional treatment is to replenish levodopa
      since it could pass through blood brain barrier and form dopamine. However, its
      accumulation can cause patients' movement disorders and uncontrollable emotion.
      Therefore, it is critical to control the levodopa dosage accuracy to improve the
      curative effect in clinical. In this study, a smartphone-based electrochemical
      detection system was developed for rapid monitoring of levodopa. The system
      involved a disposable sensor, a hand-held electrochemical detector, and a
      smartphone with designed application. Single-wall carbon nanotubes and gold
      nanoparticles modified screen-printed electrodes were used to convert and amplify
      the electrochemical current signals upon presence of levodopa molecules. The
      electrochemical detectors were used to generate electrochemical excitation
      signals and detect the resultant currents. Smartphone was connected to the
      detector, which was used to control the detector, calculate data, and plot graph
      in real-time. The smartphone-based differential pulse amperometry system was
      demonstrated to monitor levodopa at concentrations as low as 0.5 uM in human
      serum. Furthermore, it has also been verified to be able to distinguish levodopa
      from other representative substances in the body. Therefore, its performance was
      more sensitive and rapid than electrochemical workstation. With these advantages,
      the system can be used in the field of point-of-care testing (POCT) to detect
      levodopa and provide the possibility to solve clinical demand for levodopa
      detection.

PMID- 30297173
TI  - Detection of bacterial metabolism in lag-phase using impedance spectroscopy of
      agar-integrated 3D microelectrodes.
AB  - Traditional methods for detection of metabolically-active bacterial cells, while
      effective, require several days to complete. Development of sensitive electrical
      biosensors is highly desirable for rapid detection and counting of pathogens in
      food, water, or clinical samples. Herein, we develop a highly-sensitive non
      Faradaic impedance sensor which detects metabolic activity of E. coli cells in a
      mere 1 MUl of sample volume and without any sample filtration/purification. The
      three dimensional (3D) interdigitated electrodes (IDEs) along with self-assembled
      gold-nickel (Au-Ni) nanostructures significantly amplify the sensitivity by
      increasing the sensing area almost three-fold. The developed microsystem is
      integrated with an agar-based growth medium and monitors the metabolism of
      bacterial cells, enabling bacterial detection in approximately one hour after
      inoculation, i.e. in the lag-phase. Incorporation of a secondary agar layer as a
      biocompatible passivation layer protects the IDEs from potential Faradaic
      reactions and enhances sensitivity to modulation of the non-Faradaic impedance
      due to cellular metabolism. The resultant label-free sensor is capable of
      selective identification of metabolizing cells (vs. dead cells) across a wide
      linear range (10-1000 cells/MUl). These results help pave the way for rapid
      antibacterial susceptibility testing at the point-of-need, which is currently a
      major challenge in healthcare.

PMID- 30297174
TI  - Affinity sensor for haemoglobin A1c based on single-walled carbon nanotube field
      effect transistor and fructosyl amino acid binding protein.
AB  - Haemoglobin A1c (HbA1c) is a significant glycaemic marker for diabetes mellitus.
      The level of HbA1c reflects the mean blood glucose level over the prior 2-3
      months and it is useful for the assessment of therapeutic effectiveness and for
      diagnosis. In this study, we report the label-free affinity sensor for HbA1c
      based on the chemiresistor-type field-effect transistor, which has a simple
      sensor configuration. Single-walled carbon nanotubes (SWNTs) were  used as the
      transducing element. The fructosyl amino acid binding protein from Rhizobium
      radiobacter (SocA), which binds to alpha-fructosyl amino acid specifically, was
      used as the biorecognition element for fructosyl valine (FV), the product of the
      proteolytic hydrolysis of HbA1c. The developed sensor shows the ability to
      measure as low as 1.2 nM  FV, which is 14-fold more sensitive compared to the
      previously reported fluorescence-based sensor using SocA. This sensor also
      exhibits high specificity where  no significant response  is observed from 
      either fructosyl lysine (FK) or glucose, which are  potential interferents. FK is
      the epsilon-fructosyl amino acid from glycated albumin, another  glycated
      protein, whereas glucose is naturally present at  very high concentration in the
      blood. We propose that the modulation of the surface charges on the SWNTs caused
      by the conformational change in SocA upon  ligand binding leads to the
      proportionate  changes in the number of carriers in the SWNT channel.

PMID- 30297175
TI  - Preselection of Lung Cancer Cases Using FGFR1 mRNA and Gene Copy Number for
      Treatment With Ponatinib.
AB  - INTRODUCTION: Preclinically, high epidermal growth factor receptor 1 (FGFR1)
      messenger RNA (FGFR1-MRNA) and FGFR1 amplification (FGFR1-AMP) predicted
      sensitivity to fibroblast growth factor receptor inhibitors in non-small-cell
      lung cancer and small-cell lung cancer cell lines. KRAS mutations did not
      preclude sensitivity. PATIENTS AND METHODS: Metastatic EGFR- and ALK-negative
      lung cancers were screened for FGFR1-MRNA by in-situ hybridization (ISH) and
      FGFR1-AMP by silver in-situ hybridization (SISH). Patients with positive findings
      were offered ponatinib, a multi-kinase inhibitor of FGFR1-4. Differences in
      overall survival (OS) between cohorts were assessed by the log-rank test.
      Association of FGFR1 positivity with clinicopathologic features were assessed by
      Fisher exact test and Kruskal-Wallis rank sum test. RESULTS: A total of 171 cases
      were prescreened: 9 (7.3%) of 123 SISH+; 53 (42.1%) of 126 ISH+; and 6 cases
      concordantly positive for SISH and ISH. SISH+ cases had fewer coincident KRAS
      mutations (P = .03) than SISH- cases, and ISH+ cases had worse OS (P = .020) than
      ISH- cases. Data distributions suggested a distinct higher positivity cut point
      for FGFR1 ISH (>= 20%), occurring in 29 (23%) of 126 cases, was associated with
      small-cell lung cancer histology (P = .022), soft tissue metastases (P = .050)
      and shorter OS (P = .031). Four patients received ponatinib on study: All ISH+ by
      the initial cut point, 2 of 4 by higher cut point, 1 of 4 SISH+. Tolerability was
      poor. The best response for the 2 higher ISH cases was stable disease and
      progressive disease for the 2 lower ISH cases. CONCLUSION: Elevated FGFR1-MRNA is
      more common than FGFR1-AMP and associated with worse OS. Higher FGFR1 mRNA
      expression may be associated with a specific phenotype and is worthy of further
      exploration. Ponatinib's poor tolerance suggests further fibroblast growth factor
      receptor exploration in ISH+ cases should utilize more selective FGFR1
      inhibitors.

PMID- 30297176
TI  - Exploring the Diversity of Plant Metabolism.
AB  - Plants produce a huge array of metabolites, far more than those produced by most
      other organisms. Unraveling this diversity and its underlying genetic variation
      has attracted increasing research attention. Post-genomic profiling platforms
      have enabled the marriage and mining of the enormous amount of phenotypic and
      genetic diversity. We review here achievements to date and challenges remaining
      that are associated with plant metabolic research using multi-omic strategies. We
      focus mainly on strategies adopted in investigating the diversity of plant
      metabolism and its underlying features. Recent advances in linking metabotypes
      with phenotypic and genotypic traits are also discussed. Taken together, we
      conclude that exploring the diversity of metabolism could provide new insights
      into plant evolution and domestication.

PMID- 30297177
TI  - Fully covered self-expandable metallic stents for malignant airway disorders.
AB  - BACKGROUND: Airway stenting is an established procedure for treating airway
      stenosis and fistulas. The AERO stent (Merit Medical Systems, South Jordan, UT,
      USA), a relatively new, fully covered, self-expandable metallic stent, was
      approved in Japan in 2014. This study evaluated the efficacy and safety of this
      stent for malignant airway disorders. METHODS: Medical records of all patients at
      a single center, in whom the AERO stent was deployed between February 2015 and
      December 2017, were retrospectively reviewed. All procedures were performed using
      rigid and flexible bronchoscopes under general anesthesia. RESULTS: A total of 42
      procedures were performed in 36 patients: 37 for treatment of airway stenosis and
      five for tracheoesophageal fistula. The AERO stents were successfully placed in
      41 of 42 (98%) cases. The amount of oxygen could be reduced in 78% of patients
      who required oxygen therapy. Pulmonary function, including vital capacity, forced
      expiratory volume in 1 second, and peak expiratory flow, improved significantly
      after the procedures. Complications occurred in 14 (33%) cases; the most frequent
      complication was migration (6 cases). Fourteen stents were successfully removed
      without any complications. CONCLUSIONS: Placement of an AERO stent was effective
      and acceptably safe for treating malignant airway disorders. Because the AERO
      stent can be removed safely, it can be used for palliation or as a bridge to
      chemoradiotherapy.

PMID- 30297178
TI  - Medical Management of Acute Facial Paralysis.
AB  - Acute facial paralysis (FP) describes acute onset of partial or complete weakness
      of the facial muscles innervated by the facial nerve. Acute FP occurs within a
      few hours to days. The differential diagnosis is broad; however, the most common
      cause is viral-associated Bell Palsy. A comprehensive history and physical
      examination are essential in arriving at a diagnosis. Medical treatment for acute
      FP depends on the specific diagnosis; however, corticosteroids and antiviral
      medications are the cornerstone of therapy. Lack of recovery after 4 months
      should prompt further diagnostic workup.

PMID- 30297179
TI  - Management of Flaccid Facial Paralysis of Less Than Two Years' Duration.
AB  - Flaccid facial paralysis results in disfiguring facial changes. The treatment of
      flaccid facial paralysis is complex and treatment approaches should be determined
      based on duration and the causes of paralysis, status and accessibility of the
      affected facial nerve, medical comorbidities, and patient-specific goals.
      Although primary nerve repair is the preferred treatment strategy when possible,
      nerve substitution procedures are the mainstay of treatment for patients with
      flaccid facial paralysis of less than 2 years duration.

PMID- 30297180
TI  - Publicly Available Databases in Otolaryngology Quality Improvement.
AB  - The historical context for quality improvement is provided. Important differences
      are described between the two overarching types of databases: clinical registries
      and administrative databases. The pros and cons of each are provided as are
      examples of their utilization in otolaryngology-head and neck surgery.

PMID- 30297181
TI  - Delivering Otolaryngologic Care Safely and Successfully.

PMID- 30297182
TI  - Rethinking Morbidity and Mortality Conference.
AB  - This article will discuss the importance of an effective morbidity and mortality
      (M&M) conference toward supporting a proactive and preventative approach to
      patient safety and quality improvement (PSQI). Key characteristics will be
      discussed that enhance this process for being a mechanism for driving positive
      PSQI culture change that permeates the department. The focus of this article will
      be on how to approach the structure and process of this conference for maximal
      benefit.

PMID- 30297183
TI  - Multidisciplinary Tracheostomy Care: How Collaboratives Drive Quality
      Improvement.
AB  - There have been reports of successful quality-improvement initiatives surrounding
      tracheostomy care for more than a decade, but widespread adoption of best
      practices has not been universal. Five key drivers have been found to improve the
      quality of care for tracheostomy patients: multidisciplinary synchronous ward
      rounds, standardization of care protocols, appropriate interdisciplinary
      education and staff allocation, patient and family involvement, and use of data
      to drive improvement. The Global Tracheostomy Collaborative is a quality
      improvement collaborative dedicated to improving the care of tracheostomy
      patients worldwide through communication, dissemination, and implementation of
      proven strategies based on these 5 key drivers.

PMID- 30297184
TI  - Is the Birthing Unit Design Spatial Evaluation Tool valid for diverse groups?
AB  - BACKGROUND: Awareness of the impact of the built environment on health care
      outcomes and experiences has led to efforts to redesign birthing environments.
      The Birth Unit Design Spatial Evaluation Tool was developed to inform such
      improvements, but it has only been validated with caseload midwives and women
      birthing in caseload models of care. AIM: To assess the content validity of the
      tool with four new participant groups: Birth unit midwives, Aboriginal or Torres
      Strait Islander women; women who had anticipated a vaginal birth after a
      caesarean; and women from refugee or culturally and linguistically diverse
      backgrounds. METHODS: Participants completed a Likert-scale survey to rate the
      relevance of The Birth Unit Design Spatial Evaluation Tool's 69 items. Item-level
      content validity and Survey-level validity indices were calculated, with the
      achievement of validity set at >0.78 and >0.9 respectively. RESULTS: Item-level
      content validity was achieved on 37 items for birth unit midwives (n=10); 35
      items for Aboriginal or Torres Strait Islander women (n=6); 33 items for women
      who had anticipated a vaginal birth after a caesarean (n=6); and 28 items for
      women from refugee or culturally and linguistically diverse backgrounds (n=20).
      Survey-level content validity was not demonstrated in any group. CONCLUSION:
      Birth environment design remains significant to women and midwives, but the Birth
      Unit Design Spatial Evaluation Tool was not validated for these participant
      groups. Further research is needed, using innovative methodologies to address the
      subconscious level on which environment may influence experience and to
      disentangle the influence of confounding factors.

PMID- 30297185
TI  - [Surgical treatment of BPO: Standard and innovations].
AB  - INTRODUCTION AND OBJECTIVE: Surgical management of benign prostatic hyperplasia
      has dramatically changed in the recent years towards higher proportion of
      endoscopic treatment and fewer perioperative complications. Nevertheless the
      question of urinary and sexual quality of life after surgical treatment remains
      partially unresolved with a high proportion of retrograde ejaculation after
      conventional surgical treatments. Therefore mini-invasive alternatives to
      conventional surgery have been proposed. The objective of this literature review
      was to provide an overview of the alternatives to monopolar TURP currently
      available in France. MATERIAL AND METHOD: A non-systematic review of the
      scientific literature was conducted from the PubMed database to retrieve the most
      relevant scientific publications. A first research was cross-referenced with the
      results of literature reviews already published and enriched by the authors of
      this review. A synthesis is proposed for each alternative technique mentioning
      its level of clinical development, but also its potential advantages and
      disadvantages compared to conventional surgical techniques. RESULTS: The quality
      of life of patients after surgical or interventional management has become the
      main priority of urologists since the risks of perioperative complication have
      been reduced by the use of laser or bipolar endoscopic techniques. Thanks to the
      development of minimally invasive alternatives that are better and better
      evaluated by randomized trials versus interventional simulation and conventional
      surgical treatment, more personalized care is possible. Patients' expectations
      and their individual risk factors can thus be placed at the center of the
      therapeutic decision and the preoperative information. CONCLUSION: The surgical
      and interventional management of LUTS due to BPH has evolved to lower
      perioperative morbidity with the help of numerous technological developments.
      Mini-invasive alternatives to standard treatment have also been proposed in order
      to improve the quality of postoperative sexual life. These alternatives provide
      significant improvement in LUTS that remains lower than after conventional
      treatments. Somme of these alternative are also not fully supported by clinical
      trials, which should urge urologists to act with caution when proposing these
      alternatives in daily clinical practice.

PMID- 30297186
TI  - The narrow-sense and common single nucleotide polymorphism heritability of early
      repolarization.
AB  - BACKGROUND: Early repolarization (ER) is a risk marker for sudden cardiac death.
      Higher risk is associated with horizontal/descending ST-segment ER in the
      inferior or inferolateral ECG leads. Studies in family cohorts have demonstrated
      substantial heritability for the ER pattern, but genome-wide association studies
      (GWAS) have failed to identify statistically significant and replicable genetic
      signals. METHODS AND RESULTS: We assessed the narrow-sense and common single
      nucleotide polymorphism (SNP) heritability of ER and ER subtypes using ECG data
      from 5829 individuals (TwinsUK, BRIGHT and GRAPHIC cohorts). ER prevalence was
      8.3%. In 455 monozygous vs 808 dizygous twin pairs, concordances and twin
      correlations for ER subtypes (except horizontal/descending ST-segment ER) were
      higher and familial resemblance (except notched ER) was significant. Narrow-sense
      heritability estimates derived from 1263 female twin pairs using the structural
      equation program Mx ranged from 0.00-0.47 and common SNP heritability estimates
      derived from 4009 unrelated individuals of both sexes using Genome-wide
      Restricted Maximum Likelihood (GREML) ranged from 0.00-0.36, but none were
      statistically significant. CONCLUSION: From our data, ER shows limited genetic
      predisposition. There appears to be significant environmental influence and these
      modest narrow-sense and common SNP heritability estimates may explain why
      previous GWAS have been unsuccessful.

PMID- 30297187
TI  - A successful crowdfunding project for eHealth research on grown-up congenital
      heart disease patients.
AB  - BACKGROUND: Scarce data on crowdfunding report a maximal funding of ?10.000,-,
      and state that research is needed to attract attention of larger granting
      organizations. The aims of this project were 1) to fund an eHealth study in grown
      up congenital heart disease (GUCH) patients 2) to contemplate on critical success
      factors. METHODS: After peer review of the Dutch Heart Foundation a project was
      published at a donation platform, which was open for donations during a
      predetermined period of two months. Copywriters were hired to create an easy-to
      understand message to donors. A video teaser was created with a motivated
      patient, and rewards were available. The crowdfunding targeted ?25.000 and the
      Dutch Heart Foundation doubled the donations to ?50.000, and return of donations
      were guaranteed in case this was not met. RESULTS: Initially, donations came from
      the investigators' private inner circle. In total, 44 potential donors were
      contacted, but refused to donate originally. Multiple (social) media campaigns
      were published to promote the project, and an offline mailing was sent to
      contributors to the Dutch Heart Foundation. During the project support emerged,
      resulting in extra donations and public awareness. In the lasts three weeks,
      after sufficient private donations, five major donors decided to support the
      project. The project became a big success: the predetermined target was exceeded
      and a total of ?74.450,- was raised. CONCLUSION: Innovative crowdfunding gave the
      opportunity to start eHealth research in GUCH patients. Critical success factors
      include support of a professional organization, support of stakeholders, and easy
      to-understand messages.

PMID- 30297188
TI  - Cardiac resynchronization therapy in congenital heart disease: Results from the
      German National Register for Congenital Heart Defects.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is an established option for
      patients with heart failure. Limited data exists on indications and outcome of
      CRT in contemporary congenital heart disease (CHD) patients. METHODS AND RESULTS:
      All patients with CRT registered in the German National Register for Congenital
      Heart Defects were systematically identified. We analysed data on demographics,
      type of congenital defect as well as repair, associated conditions, indication
      for CRT, heart failure medication, combination with a defibrillator or pacemaker
      and outcome. Overall, 65 patients with CRT were identified. The most common
      congenital diagnoses were Tetralogy of Fallot (n = 11), congenitally corrected
      transposition of the great arteries (ccTGA) (n = 9) and double outlet right
      ventricle (n = 6). The majority of patients (n = 48, 87%) had conventional
      antibradycardia pacing or ICD indications. Of these, the majority (n = 44)
      underwent an upgrade to a CRT system to avoid the detrimental consequences of
      longstanding conventional ventricular single-site pacing, whereas four patients
      required an ICD due to heart failure and a history of malignant ventricular
      tachycardia. During a median follow-up of 6.9 years 19 patients developed
      complications: 16 patients experienced pacemaker lead dysfunction and 3 patients
      pacemaker infection. CONCLUSIONS: The current study based on a large national
      register for CHD shows that CRT is feasible and can be used as an adjunct in the
      heart failure treatment of selected CHD patients. Uptake of this therapy proved
      to be low in this nationwide study and CRT implantation was largely used in
      patients with a pre-existing pacing indication or those requiring an ICD.

PMID- 30297189
TI  - Heart failure and the risk of acute kidney injury in relation to ejection
      fraction in patients undergoing coronary artery bypass grafting.
AB  - BACKGROUND: We studied the association between heart failure with reduced or
      preserved ejection fraction (EF) and the risk of acute kidney injury (AKI) in
      patients undergoing coronary artery bypass surgery (CABG). METHODS: We included
      all patients who underwent isolated CABG in Sweden 2003 to 2013. AKI was defined
      according to the Kidney Disease Improving Global Outcomes definition, as an
      increase in postoperative serum creatinine concentration by >=26 MUmol/L or
      >=50%, compared to preoperative values. Adjusted odds ratios (OR) for AKI were
      calculated using logistic regression for patients with and without heart failure,
      and among patients with heart failure, by EF categories (<30% severely reduced;
      30-40% moderately reduced; >=50% preserved). RESULTS: Included were 36,403
      patients of whom 3914 (11%) had heart failure. In patients with heart failure,
      26% developed AKI compared with 14% in patients without heart failure. After
      adjustment for background characteristics, including preoperative kidney function
      and EF, the OR for AKI was 1.12 (95% CI 1.02-1.23) in patients with heart failure
      compared with no heart failure. Among patients with heart failure, the adjusted
      OR for AKI among patients with EF <30% vs. >=50% was 1.32 (95% CI 1.06-1.65) and
      for 30-49% vs. >=50% 1.06 (95% CI 0.87-1.28), respectively. CONCLUSION: Patients
      with heart failure who underwent CABG had an increased risk for AKI
      postoperatively even after adjustment for comorbidity such as EF. Among patients
      with heart failure, having a severely reduced EF was associated with AKI compared
      to patents with preserved EF.

PMID- 30297190
TI  - On the prospect of serum exosomal miRNA profiling and protein biomarkers for the
      diagnosis of ascending aortic dilatation in patients with bicuspid and tricuspid
      aortic valve.
AB  - BACKGROUND: To determine the impact of circulating miRNA and protein activity on
      the severity of ascending aortic dilatation in patients with bicuspid (BAV) and
      tricuspid aortic valve (TAV). METHODS: By reverse transcription polymerase chain
      reaction, exosomal circulating expression levels (versus healthy aorta) of miRNAs
      and absolute levels of transforming growth factor beta (TGF-beta), matrix
      metalloproteinases (MMP-2, -3 and -9), tissue inhibitors (TIMP-1, -2, -3 and -4),
      and soluble receptors for advanced glycation end products AGEs (sRAGE) were
      evaluated in ascending dilated aortas of 71 patients with different valve
      morphotype. RESULTS: Less-dilated ascending aorta exhibited a specific miRNA
      signature (i.e., miR-126 miR-15b, miR-195, miR-221, miR24, miR-30b and miR-320a),
      which was statistically different from that of severely-dilated ascending aorta.
      Among these analytes, miR-15b was the most significant (p < 0.001) and resulted
      as an independent predictor of aortic dilatation (beta = -1.099, p = 0.041). When
      patients were grouped according to aortic valve morphology, miRNAs and protein
      proteolytic activity were different between BAV and TAV in the expression level
      of miR-133a, miR-155, miR-320a, miR-34a(#000425), miR-34a(#000426), miR-494 and
      measurements of TGF-beta and MMP-3, MMP-9, TIMP-4. The circulating level of miR
      34a(#000426) was negatively correlated to the aortic wall elasticity of bicuspid
      patients (R = -0.653 and p = 0.011), suggesting an apparent different mechanism
      of aortic wall degeneration specific for BAV. CONCLUSIONS: Taken these biomarkers
      together, we demonstrated that the severity of aortic size and valve morphology
      differently modulates miRNA analytes and protein proteolytic activity in patients
      with ascending aortic dilatation, and this may be useful to design new therapies
      that inhibit miRNAs.

PMID- 30297191
TI  - Epicardial adipose tissue and cardiovascular diseases.
AB  - Obesity is a heterogeneous disease with different degrees of cardiovascular (CV)
      and metabolic manifestations. Certain ectopic fat depots may contribute to
      obesity-related CV risk and may explain part of the risk differential observed in
      metabolically healthy obese and the so called "obesity paradox". The growing
      interest towards the potential impact of epicardial adipose tissue (EAT) in
      cardiovascular (CV) risk has led to deepen its biological function. Genetic,
      epigenetic and environmental factors may drive the shift towards a dysfunctional
      EAT characterized by a pro-inflammatory and pro-fibrotic phenotype. Due to the
      close anatomic proximity to coronary arteries, a thicker and dysfunctional EAT
      actively contribute to development and progression of coronary atherosclerosis.
      Beside classical paracrine transmission, EAT may directly release mediators into
      the vasa vasorum of the coronary arterial wall, a mechanism referred to as
      "vasocrine". Similarly, the pro-inflammatory and pro-fibrotic secretome
      characterizing dysfunctional EAT may impair cardiac structure and function, thus
      being implicated in the pathogenesis of diastolic heart failure and atrial
      fibrillation. The development of 3D imaging techniques have paved the way for
      clarifying the causative role of EAT in CV pathophysiology, the use of EAT
      volume/thickness in CV risk stratification and potential cardio-protective
      effects of EAT reduction. The aim of this narrative review is to update current
      knowledge on the pathophysiological functions of EAT, focusing on basic
      mechanisms and potential clinical implications.

PMID- 30297192
TI  - Developing a one-step triplet-repeat primed PCR assay for diagnosing myotonic
      dystrophy.

PMID- 30297193
TI  - Coma, Seizures, Atrioventricular Block, and Hypoglycemia in an ADB-FUBINACA Body
      Packer.
AB  - BACKGROUND: Synthetic cannabinoid intoxication has become difficult to diagnose
      and manage in the United States, in part due to varying clinical effects within
      this heterogeneous group of compounds. CASE REPORT: A 38-year-old man was
      admitted with altered mental status and bradycardia. He demonstrated progressive
      encephalopathy, seizure activity, second-degree atrioventricular block type I,
      respiratory failure, hypotension, hypothermia, and hypoglycemia. A computed
      tomography scan of the abdomen and pelvis revealed multiple packages in the
      patient's stomach and rectum. Multiple attempts at gastrointestinal
      decontamination were unsuccessful. On hospital day 8 the patient developed
      hypertensive emergency and was taken to the operating room for exploratory
      laparotomy. Twenty-two poorly wrapped packages were removed from the bowel.
      Postoperatively the patient demonstrated both generalized and focal seizure
      activity. His mental status slowly returned to baseline over the period of about
      1 week and he was ultimately discharged without neurological sequelae after 1
      month. Analysis of patient serum, urine, and plant matter from the packages
      identified cannabis and 2.N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4
      fluorobenzyl)-1H-indazole-3-carboxamide (ADB-FUBINACA). WHY SHOULD AN EMERGENCY
      PHYSICIAN BE AWARE OF THIS?: The case presented demonstrates the suspected
      toxidrome associated with severe ADB-FUBINACA intoxication, including mental
      status depression, bradycardia, autonomic instability, seizure, hypoglycemia, and
      hypothermia. Although the patient had simultaneous exposure to cannabis, his
      constellation of symptoms is not consistent with cannabis intoxication. A
      previous animal model supports the potential of this specific synthetic
      cannabinoid to cause the reported toxidrome.

PMID- 30297194
TI  - Aphthous Stomatitis Major in a 4-Month-Old Infant.

PMID- 30297195
TI  - Symptomatic Arachnoid Cyst After Cervical Manipulation.

PMID- 30297196
TI  - Tophaceous Gout in the Lumbar Spine Causing Radiculopathy.
AB  - Tophaceous deposits in lumbar spine is considered a rare condition. We report the
      case of a 44-year-old patient with low back pain and radiculopathy. Radiographs
      revealed lytic spondylolisthesis in L5. Magnetic resonance imaging showed
      hypointense signal on T1 and a heterogeneous signal on T2 located in the L4-L5
      interspinous space and in the left facet joint that invades left neuroforamen.
      The left knee ultrasound showed "double contour" of the medial femoral condyle.
      Decompressive laminectomy with arthrodesis at the level of L5-S1 was performed.
      The histological examination revealed amorphous material with a foreign body
      giant cell reaction.

PMID- 30297197
TI  - Aphthous Stomatitis and Laryngitis, Another Form of Presentation of an IgG4
      Related Disease?
AB  - IgG4-related disease is characterized by a lymphoplasmacytic infiltrate rich in
      IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. It can
      present as parotid gland enlargement, tubulointerstitial nephritis,
      retroperitoneal fibrosis or pancreatitis, although nearly any organ can be
      affected. We report the case of a 37-year-old woman who presented with severe
      dysphonia and recurrent painful aphthous ulcers, with histopathological findings
      at the level of the larynx that revealed a lymphoplasmacytic infiltrate and IgG4
      positivity. In addition, extensive studies were performed to rule out other
      diseases. Thus the diagnosis was IgG4-related laryngitis, an exceptional finding
      in the literature.

PMID- 30297198
TI  - Neither the anti-nuclear antibodies nor the anti-extractable nuclear antigens Are
      What They Used to Be. A Future Change of Nomenclature.

PMID- 30297200
TI  - [Pemetrexed-induced eyelid edema].
AB  - BACKGROUND: Drug-induced eyelid edemas are rare. Herein, we describe a patient
      who developed this type of edema under chemotherapy. PATIENTS AND METHODS: A 56
      year-old male patient with a history of hypertension and adenocarcinoma of the
      lung with brain metastases consulted for incipient non-itchy eyelid edema with
      progressive worsening. The swelling occurred after 3 cycles of pemetrexed
      carboplatin. There was no evidence of any other cause of edema. A diagnosis of
      pemetrexed-induced eyelid edema was made. Given the efficacy of this treatment
      and the patient's consent thereto, it was maintained. DISCUSSION: Palpebral
      edemas secondary to pemetrexed are very rare, with only 22 published cases in the
      literature. Other differential diagnoses must be ruled out before considering
      this etiology. The pathogenesis of eyelid edema remains unknown. One hypothesis
      is capillary protein leakage inducing swelling in soft tissue and non-malignant
      effusion, as has been suggested for docetaxel. Other agents such as tyrosine
      kinase inhibitors (imatinib and nilotinib) and mTOR inhibitors (sirolimus) may
      also cause eyelid edema. Treatment of eyelid edema is difficult and one case of
      surgical treatment has been published with good results and no recurrence after 6
      months.

PMID- 30297199
TI  - Endogenous secretory RAGE increases with improvements in body composition and is
      associated with markers of adipocyte health.
AB  - BACKGROUND AND AIMS: The receptor for advanced glycation end products (RAGE) is
      implicated in obesogenesis. Conversely, soluble RAGE (sRAGE) competitively
      inhibits RAGE. Our aim was to determine the effects of weight-loss via alternate
      day fasting (ADF) on sRAGE isoforms and evaluate potential relationships with
      body composition. METHODS AND RESULTS: 42 obese participants were randomized to
      control (CON) or ADF. For 24 weeks, the ADF group consumed 25% or 125% of their
      caloric requirements on alternating days while the CON group did not change their
      diet. Body fat was measured via DXA, visceral fat (VAT) via MRI and subcutaneous
      fat (SAT) was derived by subtracting VAT from total fat. sRAGE isoforms were
      measured via ELISAs. After 24 weeks, ADF -6.8 (-9.5, -3.5)kg (Median, IQR) lost
      more weight than CON -0.3 (-1.9, 1.0)kg (p < 0.05). The change in endogenous
      secretory RAGE (esRAGE) was different between ADF 15 (-30, 78)pg/mL and CON -21 (
      72, 16)pg/mL after 24 weeks (p < 0.05). To examine the effect of changes in body
      composition, the cohort was stratified by median weight-, fat-, SAT-, and VAT
      loss. The changes in all sRAGE isoforms were different between those above and
      below median weight-loss (p < 0.05) with sRAGE isoforms tending to decrease in
      individuals below the median. Changes in total sRAGE and esRAGE were different
      between individuals above compared to below median fat- and SAT-loss (p < 0.05).
      Those above median fat-loss increased esRAGE by 29 (-5, 66)pg/mL (p < 0.05).
      CONCLUSION: Improvements in body composition are related to increased sRAGE
      isoforms, implicating sRAGE as a potential target for the treatment of obesity.
      CLINICAL TRIAL REGISTRATION: NCT00960505.

PMID- 30297201
TI  - Iatrogenic pharyngoesophageal perforations treated with fully covered self
      expandable metal stents: Case report.

PMID- 30297202
TI  - The unexpected finding: A fish bone mimicking a gastric tumour lesion.

PMID- 30297203
TI  - Hemodynamics of the uterine and umbilical arteries during the perinatal period in
      ewes.
AB  - Examining feto-maternal blood flow is extremely important for accurate prenatal
      control and predicting adverse conditions during puerperium. We aimed to analyze
      blood flow of uterine artery (UA) and umbilical artery (UMA) from and subsequent
      to mid-gestation, lambing and postpartum of 15 ewes, subjected to lambing
      induction with aglepristone. Hemodynamic variables, diameter and blood flow of UA
      and UMA were determined by Doppler and B-mode ultrasonography at 60, 90 and 120
      days of pregnancy, at 12 h before, 12 h after first aglepristone injection and 12
      h after induction and days 1, 3, 5, 7, 15 and 30 after lambing. The UMA peak
      systolic:diastolic velocity (S/D), resistance index (RI) and pulsatility index
      (PI) decreased from mid-pregnancy until 120 d, whereas peak systolic velocity
      (PSV), end diastolic velocity (EDV) and time average maximum velocity (TAMAX)
      increased towards 120 d. The UMA RI additionally decreased at 12 h after lambing
      induction. The UMA diameter and volume increased from mid-gestation until 12 h
      before lambing induction. UA PSV and TAMAX increased from 60 until 90 days of
      pregnancy, while EDV, PSV and TAMAX decreased soon after parturition, with a
      further reduction at 7 days. The UA diameter and volume decreased during
      postpartum, stabilizing by 15 days after parturition. In conclusion, pregnancy is
      marked by progressive increase in uterine and umbilical blood flow, while lambing
      acutely diminishes umbilical vascular resistance, suggesting lack of progesterone
      influence on vasodilation. Conversely, puerperium is characterized by reduction
      in uterine blood supply mostly within the first 2 weeks of postpartum in sheep.

PMID- 30297204
TI  - Supplementation of extender with coenzyme Q10 improves the function and fertility
      potential of rooster spermatozoa after cryopreservation.
AB  - The effects of coenzyme Q10 (CoQ10) has not yet been assessed for
      cryopreservation of rooster semen. The aim of this study was to evaluate the
      effect of different concentrations of CoQ10 in Lake extender for cryopreservation
      of rooster semen. The viability and apoptosis status, DNA fragmentation, abnormal
      morphology, motion parameters, membrane functionality, mitochondrial activity,
      acrosome integrity, lipid peroxidation, and fertility potential were evaluated
      after the freeze-thaw process. Semen samples were collected from ten roosters,
      twice a week, and then diluted in extender contained different concentrations of
      CoQ10 as follows: Lake without CoQ10 (control, Q 0), Lake containing 1 MUM (Q 1),
      2 MUM (Q 2), 5 MUM (Q 5), and 10 MUM (Q 10) CoQ10. Supplementation of Lake with 1
      and 2 MUM CoQ10 resulted in greater sperm viability, total motility, progressive
      motility, membrane functionality, mitochondrial activity, acrosome integrity, and
      fertility rate. Furthermore, the extent of lipid peroxidation in thawed
      spermatozoa treated with 1 and 2 MUM CoQ10 was less than with the other groups.
      Different concentrations of CoQ10 had no effect on DNA fragmentation and sperm
      morphology. Results of the present study indicate that supplementation of Lake
      extender with 1 and 2 MUM CoQ10 enhances the quality of rooster sperm after the
      freeze-thaw process.

PMID- 30297205
TI  - Outcomes of Chimney Technique for Preservation of the Left Subclavian Artery in
      Type B Aortic Dissection.
AB  - OBJECTIVE: To report outcomes of the chimney technique for preservation of the
      left subclavian artery (LSA) in patients with type B aortic dissection (TBAD).
      METHODS: A retrospective analysis was performed of a prospectively maintained
      database from August 2012 to October 2017. Primary endpoints were 30 day and
      overall mortality. Secondary endpoints were technical success, type Ia endoleak,
      chimney stent occlusion, aortic rupture, stroke, spinal cord ischaemia, and re
      intervention rate. RESULTS: A total of 159 patients (mean age 54 +/- 11 years;
      141 men) with TBAD were treated using the chimney technique for LSA
      revascularisation. Acute, subacute, and chronic TBAD accounted for 64%, 28%, and
      8% of cases, respectively. One hundred and six cases (67%) were complicated TBAD.
      One hundred and fifty-six patients (98%) were treated electively, while three
      (2%) were treated urgently because of intestinal or lower extremity ischaemia.
      The 30 day mortality and morbidity rates were 2% (3/159) and 4% (7/159),
      respectively. The technical success rate was 81% (129/159) and immediate type Ia
      endoleak occurred in 30 (19%) patients. Three major strokes, two spinal cord
      ischaemia and one aortic rupture, occurred early on. During a mean follow up of
      23 +/- 16 months (range 1-65 months), three more patients died: from aortic
      rupture, cerebral haemorrhage, and rectal cancer, respectively. Chimney stent
      occlusions were observed in four patients and all these chimney stents were self
      expanding. During follow up, two major strokes, one late type Ia endoleak and one
      re-intervention, occurred. According to the Kaplan-Meier curve, the estimated one
      and three year survival rates were 98.1 +/- 1.1% and 94.4 +/- 2.4%, respectively.
      CONCLUSION: Short and mid-term outcomes in the present study demonstrate that the
      chimney technique is safe and feasible for preservation of the LSA in patients
      with TBAD, but the durability of chimney stent needs to be evaluated carefully
      and immediate type Ia endoleak is a concern.

PMID- 30297206
TI  - tsRNAs: The Swiss Army Knife for Translational Regulation.
AB  - tRNA-derived small RNAs (tsRNAs, or tRFs) are a new category of regulatory
      noncoding RNAs with versatile functions. Recent emerging studies have begun to
      unveil distinct features of tsRNAs based on their sequence, RNA modifications,
      and structures that differentially impact their functions towards regulating
      multiple aspects of translational control and ribosome biogenesis.

PMID- 30297207
TI  - 'Nonlinear' Biochemistry of Nucleosome Detergents.
AB  - The transcriptional activation domains (TADs) are critical for life, yet
      intrinsically disordered polypeptides with no specific consensus sequence,
      interacting with multiple targets via low-specificity fuzzy contacts. The recent
      integration of machine learning approaches in biochemistry allows analysis of
      large experimental datasets of functional TADs as a whole and clear observation
      of TAD features. The emerging picture describes TADs as sequences without
      consensus but with a variety of detergent-like mini-motifs enriched in negatively
      charged and aromatic amino acids. Comparison of the canonical direct coactivator
      recruitment model and a new model describing TADs as nucleosome detergents that
      trigger chromatin remodeling during gene activation helps solve a fundamental
      enigma of molecular biology spanning 30 years.

PMID- 30297208
TI  - Long-term effects of unilateral deep brain stimulation on voice tremor in
      patients with essential tremor.
AB  - INTRODUCTION: Voice tremor (VT) is a common symptom of Essential tremor (ET).
      Deep brain stimulation (DBS) is an established treatment for ET overall, however,
      its effect on VT is less clear. The aim of this study was to evaluate long-term
      effects of DBS on VT and to investigate how VT symptoms develop over time in
      patients with ET. METHODS: VT scores for the cohort of 81 ET patients that had
      undergone DBS surgery in the caudal zona incerta (cZi) were analyzed
      retrospectively. Thirty-four patients had preoperative VT and long-term
      evaluations were available for 19 patients. Longitudinal effects of cZi-DBS were
      investigated 1, 3 and 5 years postoperatively. VT progression was evaluated based
      on preoperative-, and off stimulation postoperative assessments. RESULTS:
      Unilateral cZi-DBS reduced average voice tremor by 58% at the 3-year follow-up
      and by 67% 5 years after surgery. Four patterns of VT development were identified
      among patients, and the effectiveness of cZi-DBS in alleviating voice tremor
      symptoms showed differing patterns for these subgroups. CONCLUSIONS: This
      retrospective analysis of a small cohort of patients suggests that cZi-DBS may
      reduce VT in the long-term for patients with ET overall, but the pattern of VT
      progression likely influences the effectiveness of the treatment. These results
      also suggest that unilateral cZi-DBS may be more efficacious when treating
      patients with mild to moderate VT. A prospective, blinded, controlled clinical
      trial in patients with ET is needed to determine developmental patterns of VT,
      and the safety and efficacy of cZi-DBS for the treatment of VT.

PMID- 30297209
TI  - TSFM mutations cause a complex hyperkinetic movement disorder with strong relief
      by cannabinoids.

PMID- 30297210
TI  - Naftazone in advanced Parkinson's disease: An acute L-DOPA challenge randomized
      controlled trial.
AB  - INTRODUCTION: There is an unmet need to better control motor complications in
      Parkinson's disease (PD). Naftazone, which exhibits glutamate release inhibition
      properties, has shown antiparkinsonian and antidyskinetic activity in preclinical
      models of PD and in a clinical proof of concept study. METHODS: We conducted a
      double-blind randomized placebo-controlled cross-over trial in PD patients with
      motor fluctuations and dyskinesia testing naftazone 160 mg/day versus placebo for
      14 days. The two co-primary endpoints were the area under curve (AUC) of motor
      (MDS-UPDRS part III) and dyskinesia (AIMS) scores during an acute levodopa
      challenge performed at the end of each period. Secondary endpoints were UDysRS
      and axial symptoms scores during the challenge; AIMS, UDysRS, and time spent with
      or without dyskinesia the day before the challenge. The primary analysis was
      performed in the per protocol population. RESULTS: Sixteen patients were included
      in the analysis. There was no difference between naftazone and placebo for the
      AUC of MDS-UPDRS III (-89, 95%CI[-1071; 893], p = 0.85), and AIMS (70, 95%CI[
      192; 332], p = 0.57). At the end of treatment periods, AIMS score tended to be
      lower with naftazone than placebo (4.4 +/- 3.4 versus 6.7 +/- 4.4, p = 0.07), but
      UDysRS scores and other secondary outcomes were not different. Naftazone was safe
      and well tolerated. CONCLUSIONS: This study did not confirm previous results on
      the efficacy of naftazone on dyskinesia nor motor fluctuations highlighting the
      problem of translating results obtained in preclinical models into clinical
      trials. Further investigation of naftazone may be conducted in PD with longer
      treatment duration.

PMID- 30297211
TI  - Predictors of self-perceived stigma in Parkinson's disease.
AB  - OBJECTIVE: The burden of PD extends beyond physical limitations and includes
      significant psychosocial adjustments as individuals undergo changes to their self
      perception and how others perceive them. There is limited quantitative evidence
      of the factors that contribute to self-perceived stigma, which we addressed in
      the present study. METHODS: In 362 individuals with PD (157 women, 205 men), self
      perceived stigma was measured by the four-item stigma subscale of the Parkinson's
      Disease Questionnaire (PDQ-39). Hierarchical linear modeling was used to assess
      predictors of stigma including demographics (age, gender) and disease
      characteristics: duration, stage (Hoehn & Yahr Scale), motor severity (Unified
      Parkinson's Disease Rating Scale, UPDRS, Part 3), activities of daily living
      (UPDRS Part 2), and depression (Geriatric Depression Scale). Predictor variables
      were chosen based on their significant correlations with the stigma subscale.
      Further analyses were conducted for men and women separately. RESULTS: For the
      total sample, the full model accounted for 14% of the variance in stigma
      perception (p < .001). Younger age and higher depression scores were the only
      significant predictors (both p < .001). This pattern was also seen for the men in
      the sample. For the women, only depression was a significant predictor.
      Depression mediated the relation between stigma and activities of daily living.
      CONCLUSIONS: Younger age (men) and depression (men and women) were the primary
      predictors of self-perceived stigma in PD. Disease characteristics (motor and
      ADL) did not contribute to stigma perception. Depression is a potential treatment
      target for self-perceived stigma in PD.

PMID- 30297212
TI  - Phosphorylated alpha-synuclein deposits in sural nerve deriving from Schwann
      cells: A biomarker for Parkinson's disease.
AB  - INTRODUCTION: Paresthesia is common in Parkinson's disease (PD) patients. We
      assumed that peripheral nerve might be implicated. This study aimed to
      investigate whether phosphorylated alpha-synuclein (pSNCA) pathology occurred in
      sural nerve fibers and to explore the underlying pathogenesis of paresthesia of
      lower limbs associated with PD. METHODS: Clinical assessments and sural nerve
      biopsy were performed to evaluate clinical characteristics and the deposition of
      total alpha-synuclein (tSNCA) and pSNCA in biopsy pieces using immunochemistry
      methods on 16 PD patients and 15 controls. In addition, immunofluorescence
      staining was performed using certain antibodies to characterize the component of
      sural nerve and to localize the expression of pSNCA. RESULTS: Deposition of pSNCA
      was found in 16/16 PD patients with a high positive percentage of 100% but in
      0/15 controls, however, all biopsy pieces showed positive response to tSNCA
      immunohistological staining in nerve fibers. pSNCA was expressed mainly in
      Schwann cells but scarcely in axons, demonstrating a novel pattern of pSNCA
      expression in peripheral nervous system. CONCLUSION: Our findings suggest that
      peripheral somatic sensory nerve is also involved in SNCA pathology in PD. The
      search for pSNCA in sural nerve might serve as a novel biomarker for early
      diagnosis of PD and pSNCA in sural nerve may derive from Schwann cells rather
      than propagate retrograde along the primary sensory neurons from the central
      nervous system.

PMID- 30297213
TI  - Dentate nucleus stimulation in a patient with cerebellar ataxia and tremor after
      cerebellar stroke: A long-term follow-up.

PMID- 30297214
TI  - Combined antifungal therapy is superior to monotherapy in pulmonary
      scedosporiosis in cystic fibrosis.
AB  - Cystic fibrosis (CF) is characterised by chronic airway infection with bacteria
      and fungi. Infections caused by Scedosporium/Lomentospora species can occur and
      are difficult to treat. Moulds belonging to the genus Scedosporium/Lomentospora
      are detected most frequently in respiratory samples of patients with CF, next to
      Aspergillus spp. Our aim was to define pulmonary fungal infections due to
      Scedosporium/Lomentospora in CF and to study the antimycotic treatment. In this
      multicentre study (12 centres; duration January 2008 to December 2014) 31
      patients with a lung infection caused by moulds of the genus
      Scedosporium/Lomentospora were included. 36 courses of antifungal treatment were
      documented. Scedosporium apiospermum sensu stricto accounted for 48.4% of cases.
      In 20/31 patients a therapeutic response under antimycotics (median duration 3.9
      months) was achieved. Triple and double therapy was significantly more effective
      compared to monotherapy regarding FEV1, radiology, and symptoms. This data
      suggests that combined treatment is superior to monotherapy in patients with CF.

PMID- 30297215
TI  - How does ballet training alter ankle tendinous morphology and hemodynamics in
      asymptomatic pre-professional dancers? An ultrasonographic study.
AB  - OBJECTIVES: Among symptomatic dancers, sonographic abnormalities are common.
      Whether asymptomatic dancers have any abnormalities remains unknown. Some dancers
      became cyanosis over distal feet after ballet training. The hemodynamic changes
      at the feet in ballet are not clearly understood. DESIGN: Cross-sectional study.
      METHODS: In 25 dancers and 14 non-dancers, B-mode ultrasonography was used to
      measure cross-sectional areas (CSA) of tendons of deep posterior compartment
      muscles. Doppler ultrasonography was used to measure peak velocity (Vpeak) of
      posterior tibial artery in three ankle postures: the neutral position, passively
      and forced actively plantar flexion (en pointe). The big toe oxygen saturation
      was recorded in neutral position and during 1-min en pointe. Single-leg standing
      heel rise test was performed to represent the muscle function. RESULTS: The CSA
      of FHL was larger in dancers (0.26cm2 [0.20, 0.30] vs 0.21cm2 [0.17, 0.24],
      p<0.01), while other tendons were not different (all p>0.05). Higher Vpeak was
      recorded in passively plantar flexion than in neutral position (p<0.01, in both
      groups). The blood flow was undetectable during en pointe, more frequently in
      dancers (54.9% vs 14.3%, p<0.01). Oxygen saturation decreased during en pointe
      more prominently in dancers (85% [80, 90] vs 94% [84, 97], p<0.01). There was no
      significant difference in muscle function. CONCLUSIONS: US showed the FHL tendon
      thickening and en pointe-related vascular compromise in pre-professional dancers,
      even when they are asymptomatic.

PMID- 30297216
TI  - The effects of recovery duration on physiological and perceptual responses of
      trained runners during four self-paced HIIT sessions.
AB  - OBJECTIVES: This study aimed to examine the effects of different recovery
      durations on self-selected running velocities, physiological responses, and
      ratings of perceived exertion (RPE) in a commonly used high intensity interval
      training (HIIT) protocol. DESIGN & METHODS: Twelve trained runners performed an
      incremental treadmill exercise test to determine maximal oxygen uptake (VO2max)
      and heart rate (HRmax). In four subsequent visits, participants performed a HIIT
      session comprising six 4-min work intervals, in which the recovery duration
      between work intervals equalled either a fixed (1MIN, 2MIN, 3MIN) or a self
      selected duration (ssMIN). HIIT sessions were run on a non-motorized treadmill,
      and were performed under isoeffort conditions. RESULTS: Mean running velocity was
      significantly higher in 3MIN compared with all other protocols, and higher in
      ssMIN compared with 2MIN. No significant differences in time spent >=90% and 95%
      VO2max, or >=90% and 95% HRmax were evident between the four protocols. RPE
      responses were similar across and within the protocols showing a gradual increase
      with each progressive interval. CONCLUSION: In a self-paced HIIT session of six 4
      min work intervals, the length of recovery durations had a limited effect on the
      total physiological strain endured in the training. However, running velocities
      were higher when participants received the longest recovery period (3MIN). Longer
      recovery durations may facilitate a higher external training load (faster
      running), whilst maintaining a similar internal training load (physiological
      stimulus), and may therefore allow for greater training adaptations.

PMID- 30297217
TI  - Characteristics of Neovascularization in Early Stages of Proliferative Diabetic
      Retinopathy by Optical Coherence Tomography Angiography.

PMID- 30297218
TI  - Elastin Content and Distribution in Endothelial Keratoplasty Tissue Determines
      Direction of Scrolling.

PMID- 30297219
TI  - Ellipsoid Zone Change According to Glaucoma-Stage Advancement.

PMID- 30297220
TI  - On the observation of lubrication mechanisms within hip joint replacements. Part
      I: Hard-on-soft bearing pairs.
AB  - The present study describes the lubrication mechanisms within artificial hip
      joints considering real conformity of rubbing surfaces. Part I is focused on hard
      on-soft material combination, introducing the fundamentals of lubrication
      performance. These pairs have not been explored in terms of in situ observation
      before. The contact of metal femoral component articulating with transparent
      polymer acetabular cup was studied using a hip joint simulator. The film
      formation was evaluated by fluorescent microscopy method. Various model synovial
      fluids were employed while the key constituents, i.e. albumin, gamma-globulin,
      and hyaluronic acid were fluorescently stained to determine its role in film
      formation process. Two types of the tests were performed. The first dynamic test
      aimed on the development of film thickness under constant load during motor
      driven swinging motion mimicking flexion-extension. Subsequently, a combined test
      was designed consisting of the three phases; static part with loading/unloading
      phase (1), pendulum swinging till spontaneous damping of the motion due to
      friction (2), and static observation under the constant load (3). The results
      clearly confirmed that the interaction of constituents of synovial fluid plays a
      dominant role and substantially influences the lubrication conditions. In
      particular, the main finding coming from the present study is that gamma-globulin
      together with hyaluronic acid form relatively thin stable boundary layer enabling
      the enhanced adsorption of albumin, thus increasing the lubricant film. Part II
      of the present study is focused on hard-on-hard pairs while the main differences
      in film formation process are highlighted among others.

PMID- 30297221
TI  - The Impact of Lymphovascular Invasion on Risk of Upstaging and Lymph Node
      Metastasis at the Time of Radical Cystectomy.
AB  - BACKGROUND: Lymphovascular invasion (LVI) in muscle-invasive bladder cancer is
      associated with a poor prognosis when identified from radical cystectomy (RC)
      specimens. However, LVI is not clearly emphasized in any risk models to guide
      clinical decision-making. The impact of LVI on the risk of lymph node (LN)
      metastasis after a transurethral resection of bladder tumor (TURBT) specimen is
      less understood. OBJECTIVE: The goal was to describe the impact of LVI and the
      risk of LN metastasis at each clinical stage of urothelial carcinoma of the
      bladder (UC). DESIGN, SETTING, AND PARTICIPANTS: The National Cancer Database was
      queried for patients with bladder cancer who underwent RC with LN dissection from
      2004 to 2014. Patients with non-bladder primary, non-UC histology, clinical
      metastatic disease, and having received chemotherapy/radiation were excluded.
      Pathologic LN positive rates at RC were determined. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: The primary outcome was pathologic upstaging at RC and
      pathologic node positivity. Secondary outcomes included determining overall
      survival (OS). All hypotheses testing were two-sided and a p value of <0.05 was
      considered statistically significant. All statistical analyses were performed
      using Stata version 13.1. RESULTS AND LIMITATIONS: A total of 3007 patients with
      UC underwent RC with pelvic LN dissection. In patients with LVI, the risk of LN
      metastasis was significantly higher at each clinical stage as was the rate of
      pathologic upstaging. Patients with LVI on TURBT had worse OS stage for stage in
      pure UC (p<0.001). Limitations include that there was no central pathologic
      review and the number of TURBTs per patient was not known. CONCLUSIONS: Patients
      with UC with LVI had worse OS and are at higher risk for LN-positive disease and
      pathologic upstaging at surgery than patients without LVI. PATIENT SUMMARY: In
      this report we examined the impact of lymphovascular invasion (LVI) at
      transurethral resection of bladder tumor on pathologic upstaging and lymph node
      metastasis at radical cystectomy using the National Cancer Database. We
      identified LVI as being prognostic at each stage of urothelial carcinoma.

PMID- 30297222
TI  - Semi-continuous mono-digestion of OFMSW and Co-digestion of OFMSW with beech
      sawdust: Assessment of the maximum operational total solid content.
AB  - In this study, mono-digestion of the organic fraction of municipal solid waste
      (OFMSW) and co-digestion of OFMSW with beech sawdust, simulating green waste,
      were used to investigate the maximum operational total solid (TS) content in semi
      continuous high-solids anaerobic digestion (HS-AD). To alleviate substrate
      overloading in HS-AD, the effluent mass was relatively reduced compared to the
      influent mass, extending the mass retention time. To this aim, the reactor mass
      was daily evaluated, permitting to assess the reactor content removal by biogas
      production. During mono-digestion of OFMSW, the NH3 inhibition and the rapid TS
      removal prevented to maintain HS-AD conditions (i.e. TS >= 10%), without
      exacerbating the risk of reactor acidification. In contrast, the inclusion of
      sawdust in OFMSW permitted to operate HS-AD up to 30% TS, before acidification
      occurred. Therefore, including a lignocellulosic substrate in OFMSW can prevent
      acidification and stabilize HS-AD at very high TS contents (i.e. 20-30%).

PMID- 30297224
TI  - Editorial overview: Pharmaceutical biotechnology.

PMID- 30297223
TI  - Factors influencing the accuracy of ground-based tree-height measurements for
      major European tree species.
AB  - Tree height is one of the most important forest characteristics and is one of the
      crucial measurements taken for either practical or scientific reasons. However,
      the accuracy of a tree-height measurement may vary in relation to many factors.
      The work described here thus sought to evaluate the accuracy of ground-based tree
      height measurements for major forest-forming tree species of the temperate and
      boreal zones. The focus was on the importance of factors affecting accuracy of
      the measurements in question at larger geographical scales. In line with the
      above research goals, data were gathered from 299 stands throughout Poland and
      heights of 2388 sample trees of eight species, growing in different stands and
      site conditions, were measured; heights were then compared with measured lengths
      of felled trees as a reference. In total, 10 variables to determine factors that
      may influence ground-based tree-height measurement accuracy were used. We merged
      them into 4 groups: measurements, topography, stand and biometric-related
      factors. Results showed that biometric and topographic factors had the greatest
      relative influence on the accuracy of measurements of tree height. Tree length
      and species, followed by the slope of the terrain, tree age, and height above sea
      level were the most important factors found to affect accuracy. In most of the
      cases studied the terrestrial tree-height measurements were underestimated when
      set against definitive measurements of length. This was true for all species
      studied except oak, for which height measurements were typically overestimated.
      Notwithstanding the broad geographical scope of the work, the particular device
      used and the team factor were only found to have a marginal influence on
      measurement accuracy.

PMID- 30297225
TI  - Gender identity in patients with 5-alpha reductase deficiency raised as females.
AB  - BACKGROUND AND OBJECTIVE: 5-Alpha reductase type 2 deficiency (5-ARD) is a rare
      disorder of sex development. The lack of 5-alpha reductase, an enzyme that
      converts testosterone into dihydrotestosterone, results in external genitalia
      that may appear female, or predominantly male, albeit undervirilized, or, more
      often, ambiguous. METHODS: This study describes a series of patients with 5-ARD
      raised as female, focusing on aspects related to gender identity. Following a
      retrospective chart review, patients with 5-ARD were invited to return to the
      clinic to enable their gender identity to be assessed using an 11-item structured
      in-house questionnaire. The Golombok-Rust Inventory of Sexual Satisfaction was
      applied to patients who had initiated their sexual life. RESULTS: Six patients
      aged >15 years with 5-ARD and raised as female were included. Most patients were
      diagnosed late: two before and four after puberty. The mean length of the phallus
      was 2.8 cm (0.5-5.0). Reasons for seeing a doctor included genital appearance (n
      = 3), amenorrhea/absence of breast development (n = 2), and changes in gender
      role attitudes (n = 1). According to the gender identity assessment, 4 patients
      identified as female, 1 as male, and 1 as both genders. Only the patient
      identified as male requested gender re-assignment. Of the two patients who had
      initiated their sexual life, sexual satisfaction was found to be good in one and
      poor in the other due to vaginal discomfort during intercourse. CONCLUSION: In
      the present series, the majority of undervirilized patients with a diagnosis of 5
      ARD raised as female were in complete conformation with being female and
      described themselves as heterosexual. The more virilized patients were those
      least in conformity with their female-assigned gender.

PMID- 30297226
TI  - Assessment of pediatric bowel and bladder dysfunction: a critical appraisal of
      the literature.
AB  - OBJECTIVE: Bowel and bladder dysfunction (BBD) is a clinical syndrome defined by
      the coexistence of constipation and lower urinary tract symptoms. Although BBD is
      a common condition in pediatric urology and can cause significant stress to
      patients/parents, clinical diagnosis of BBD has not been standardized. Bowel and
      bladder dysfunction instruments have gained popularity over the past decade to
      aid in diagnosis. In this review, the currently published BBD symptom
      questionnaires were summarized and an analysis on their psychometric validation
      process was provided. SUBJECTS/PATIENTS: PubMed was searched for articles on BBD
      symptom questionnaires/instruments/surveys since 2000. Two investigators (R.Y.J.
      & M.S.K.) conducted the search in duplicate. The search was limited to English
      language. The included search terms were 'dysfunctional elimination syndrome',
      'bowel and bladder dysfunction', 'dysfunctional voiding', 'voiding dysfunction
      symptom score', and 'dysfunctional voiding symptom scale'. Reference lists of
      included studies were screened for missed studies. Unpublished abstracts
      presented at the following scientific meetings were also manually searched for:
      the American Urological Association, the Society for Pediatric Urology, and the
      American Academy of Pediatrics Section on Urology. Exclusion criteria included
      articles in languages other than English, articles not related to BBD
      questionnaires, and articles not pertaining to pediatric patients. RESULTS: After
      initial search, a total of 54 articles were obtained. Of the seven questionnaires
      reviewed, only one did not measure sensitivity or specificity. Almost all
      questionnaires showed excellent discriminative property with an Area under the
      curve (AUC) >0.85. Criterion validity was not reported in any of the
      questionnaires. Known-group validation was used as a common method to evaluate
      construct validity. Internal consistency was reported in 2 studies, and only 1
      study measured questionnaire responsiveness during initial validation.
      CONCLUSIONS: Although BBD is a common pediatric urology condition; a large amount
      of heterogeneity exists in the questionnaires' psychometric testing and
      validation process. To further improve the diagnosis and management of BBD in
      pediatric patients, there is a need for consensus on the gold standard
      questionnaire measure.

PMID- 30297227
TI  - How to apply for a research grant: 10 tips and tricks.

PMID- 30297228
TI  - Perineal hypospadias: back to the future Chordee Excision & Distal Urethroplasty.
AB  - PURPOSE: Perineal hypospadias correction has swung from two-stage repair in the
      1960s to one-stage repair in the 1980s and back to two-stage repair in the 2000s.
      The author's experience with a technique in which Chordee Excision and Distal
      Urethroplasty (CEDU) was performed at the first operation leaving a 1-cm segment
      as perineal urethrotomy to be reconstructed at the second operation is presented.
      PATIENTS AND METHODS: Between January 2013 and December 2016, the CEDU technique
      was performed in 63 patients with perineal hypospadias. The records of 59
      patients who maintained regular follow-up were reviewed. The principle is to
      excise the hypoplastic urethral plate, atretic corpus spongiosum, and
      longitudinal layer of tunica albuginea; split the glans in the midline; and
      reconstruct a healthy urethral plate using preputial and lateral skin flaps to
      the tip of the glans. Distal urethroplasty was performed leaving 1 cm at the
      proximal end to be reconstructed 3-6 months later. This principle was used by
      Duplay in the 1880s. Patient age ranged between 6 months and 2 years (mean 8
      months). All the patients had perineal hypospadias and bifid scrotum with severe
      deep chordee. Follow-up period ranged from 17 to 53 months (mean 36). A
      transurethral Silastic catheter was inserted for 4 days. Three months later, the
      remaining 1 cm of the new urethra was reconstructed, and final adjustment of the
      glans and foreskin was performed. RESULTS: Satisfactory results were obtained in
      54 patients (90%). Three children experienced glans dehiscence that was corrected
      in the second stage, one child developed fistula after the second operation, and
      one developed diverticulum. The fistula and diverticulum were corrected at the
      third operation successfully. DISCUSSION: It was necessary in this series to
      divide the urethral plate and excise the hypoplastic corpus spongiosum and the
      outer longitudinal layer of tunica albuginea to correct the associated deep
      chordee. The lateral skin flaps receive double blood supply from the base of the
      penis and the preputial vessels. This natural urinary diversion allows early
      removal of the catheter, reduces the discomfort of the patient, and allows the
      new urethra to heal without urine irritation for 3 months. Long-term follow-up
      for 15 years is necessary to assess the technique objectively. CONCLUSIONS: The
      CEDU technique diverts urine away from the site of urethroplasty for 3 months
      without a catheter. It reduces the hospital stay and patient discomfort. It
      produces satisfactory results and has become a the standard technique in perineal
      hypospadias.

PMID- 30297229
TI  - Small cell neuroendocrine carcinoma of the alveolar process of maxilla.

PMID- 30297230
TI  - Do temporal scores of motivational constructs correspond with physical activity
      levels?
AB  - BACKGROUND: Adults with physical disabilities typically engage in low levels of
      physical activity (PA), thus a better understanding of how motivational factors
      and behavior vary over time and in relation to disability type and severity is
      needed. OBJECTIVE/HYPOTHESIS: To examine temporal changes in theory of planned
      behavior (TPB) constructs and PA by disability type (multiple sclerosis vs.
      spinal cord injury) and severity (mild, moderate, and severe). METHODS:
      Participants were 77 adults with physical disabilities who completed a web-based
      survey that assessed the TPB constructs and PA participation. The survey was
      completed once every four months for a total of three time points. Two-way
      repeated measures ANOVAs were used to examine if the TPB constructs and PA
      changed over time and in relation to disability type and severity. RESULTS: There
      was only one significant between-subjects effect for PA by disability severity, F
      (2, 68) = 5.94, p = .004, eta2 = 15%. People with mild disabilities exhibited
      higher mean PA participation over the three time periods (M = 21.06 +/- 11.49 MET
      hrs/day) than those with moderate disabilities (M = 11.27 +/- 9.3 MET-hrs/day)
      and severe disabilities (M = 13.43 +/- 14.74 MET-hrs/day). CONCLUSIONS: Although
      participants possessed positive PA motivational factors that remained stable over
      time, their PA participation was low and differed as a function of disability
      severity. Therefore, PA interventions should be tailored such that individuals
      with severe disabilities receive the greatest amount of exercise prescription
      consultations and supervision compared to those with more moderate and mild
      disabilities.

PMID- 30297231
TI  - Primary versus secondary intraocular lens implantation in traumatic cataract
      after open-globe injury in pediatric patients.
AB  - PURPOSE: To compare the visual and refractive outcomes and complications of
      primary and secondary intraocular lens (IOL) implantation after open-globe injury
      in pediatric patients. SETTING: Sadguru Netra Chikitsalaya, Madhya Pradesh,
      India. DESIGN: Retrospective case series. METHODS: Patients had primary cataract
      extraction with IOL implantation with globe repair (Group A) or repair followed
      by secondary IOL implantation (Group B). Preoperative and surgery data, visual
      outcomes, and postoperative complications were recorded. RESULTS: The study
      included 139 patients. Thirty (49%) of 61 patients in Group A and 47 (60%) of 78
      patients in Group B achieved a corrected distance visual acuity (CDVA) of 20/40
      or better. In both groups, a central corneal scar and amblyopia were the main
      reasons for not achieving a CDVA better than 20/40. The mean spherical equivalent
      (SE) was 1.81 diopters (D) in Group A and 1.55 D in Group B. Forty patients (66%)
      in Group A and in 60 patients (77%) in Group B achieved a desirable refractive
      outcome (SE <2.00 D). A large wound was the greatest risk factor for not
      obtaining desirable refractive outcomes. Fibrinous uveitis was the most common
      postoperative complication in both groups. Pupillary optic capture and IOL
      decentration were significantly more common in Group A than in Group B (P = .02),
      while strabismus was significantly more common in Group B (P = .04). CONCLUSIONS:
      Both approaches had satisfactory and comparable visual and refractive outcomes.
      However, primary IOL implantation can be considered in cases with small
      peripheral corneal lacerations with the goal of providing early visual
      rehabilitation and avoiding repeat general anesthesia.

PMID- 30297232
TI  - Femtosecond-assisted LASIK flaps resistant to lift secondary to corneal
      epithelial defects: Case reports and ex vivo studies.
AB  - PURPOSE: To evaluate why epithelial defects created before femtosecond laser
      ablation result in laser in situ keratomileusis (LASIK) flaps resistant to lift.
      SETTING: Boston Eye Group, Brookline, Massachusetts, USA. DESIGN: Case reports
      and ex vivo studies. METHODS: To examine the mechanism of resistance to flap lift
      after epithelial defects, flap creation with a femtosecond laser was performed in
      30 fresh porcine eyes. Before ablation, the eyes were assigned to 3 groups. Group
      1 was a control group with intact corneal epithelium. In Group 2, a central 2.0
      mm corneal epithelial defect was created by marking it with a 2.0 mm trephine. In
      Group 3, a peripheral 2.0 mm epithelial defect was created similarly. After the
      femtosecond laser procedure was performed, the flaps were lifted and the
      resistance to lift was documented. The corneas were further examined using
      anterior segment optical coherence tomography. RESULTS: In Group 1, no resistance
      was felt during flap lifts. In Group 2, significant resistance was encountered at
      the edge of the epithelial defects and the flaps could not be lifted in 7 of 10
      eyes. In Group 3, similar significant resistance was encountered in all 10 eyes.
      Six of 10 flaps could not be lifted. Anterior segment optical coherence
      tomography from a representative cornea from Group 2 demonstrated a deeper
      dissection plane in the area where the overlying epithelium was missing.
      CONCLUSION: Epithelial defects can interfere with proper LASIK flap creation with
      the femtosecond laser. This seems to be attributable to a deeper cutting plane
      under the area of the epithelial defects compared with the surrounding area with
      intact epithelium.

PMID- 30297233
TI  - Separation performance of a star-shaped truxene-based stationary phase
      functionalized with peripheral 3,4-ethylenedioxythiophene moieties for capillary
      gas chromatography.
AB  - This work describes the separation performance of a star-shaped truxene-based
      material (denoted as EDOTT) as the stationary phase for capillary gas
      chromatography (GC). The EDOTT capillary column achieved the column efficiency of
      5920 plates/m by n-dodecane, 4890 plates/m by naphthalene and 3960 plates/m by 1
      octanol at 120 C. Its selectivity and retention behaviour were investigated by a
      number of mixtures of diverse analytes and their isomers. As a result, it showed
      advantageous performance for separations of apolar to polar analytes, especially
      phenols and alcohols, over its analogous TTT, TDT and TFT stationary phases. In
      addition, the EDOTT capillary column was investigated for its column loadability,
      repeatability and thermal stability, and was finally applied for the
      determination of isomer impurities in real samples. This work provides an
      alternative truxene-based stationary phase with high selectivity for polar
      analytes and demonstrates the key role of structural modification in developing a
      family of stationary phases with specific selectivity for targeted analytes.

PMID- 30297235
TI  - Accurate quantification of beta-hexosaminidase released from laboratory of
      allergic diseases 2 cells via liquid chromatography tandem mass spectrometry
      method.
AB  - beta-Hexosaminidase is one of the enzymes that is secreted from mast cells via
      antigen-induced degranulation and has frequently been used as an indicator of
      anaphylactic reactions. The main method for determining beta-hexosaminidase is
      indirect, "substrate-based" and shows limitations. Hence, development of an
      accurate detecting method is particularly important and urgently needed. In this
      study we developed a liquid chromatography tandem mass spectrometry (LC-MS/MS)
      method for measuring beta-hexosaminidase. Laboratory of allergic diseases 2
      (LAD2) cells were stimulated with compound 48/80 (C48/80), the supernatant was
      collected and subjected to in-solution protein digestion; the obtained peptides
      were desalted, concentrated, separated and analyzed with an LC-tandem MS
      instrument. A peptide with the sequence "LAPGTIVEVWK" was selected for
      quantitative analysis, and four other peptides for qualitative research. The time
      effect relationship curve was studied, and the results of the LC-MS/MS method
      were found to be almost consistent with those obtained via the conventional
      method. The method was then employed to measure beta-hexosaminidase released from
      LAD2 cells stimulated with potential allergens, and the results showed that it
      can be applied to determine the potential allergenicity of drugs. This new method
      showed good specificity, high sensitivity and a wide application range. It could
      be used to evaluate allergic reactions, providing a guide for medication safety
      during clinical testing.

PMID- 30297234
TI  - Aqueous extraction followed by derivatization and liquid chromatography-mass
      spectrometry analysis: A unique strategy for trace detection and identification
      of G-nerve agents in environmental matrices.
AB  - A highly sensitive method for the detection and identification of sarin (GB),
      soman (GD) and cyclosarin (GF) chemical warfare agents (CWAs) in environmental
      outdoor and indoor matrices such as soil, asphalt, linoleum, formica, concrete
      and cloth was developed. The method incorporates derivatization of the G-type
      nerve agent extracts with 2-[(dimethylamino)methyl]phenol (2-DMAMP), followed by
      LC-ESI(+)-MS/MS analysis. Four LC-amenable extraction solvents were explored in
      terms of their extraction efficiency and the reaction rate of the derivatizing
      agent. The reaction time, temperature and derivatization reagent amount were
      optimized. The optimal procedure was found to be extraction with water by
      agitation (2 min), followed by the addition of 2-DMAMP directly into the
      injection vial and stirring for 5 min prior to LC-ESI(+)-MS/MS analysis, without
      any other pretreatment. The method was applied to real-world samples and
      exhibited very low detection limits (LODs) of 0.8-20 pg/cm2 in asphalt, linoleum,
      cloth, formica and concrete and 4 pg/g in soil. The newly developed method
      demonstrated significantly superior sensitivity compared to conventional GC-MS-
      and LC-MS-based methods for the identification of G-nerve agents and allowed the
      determination of both G-nerve agents and their hydrolysis products within a
      single LC-MS/MS run. The proposed methodology may be practical for verifying
      contaminated matrices collected in the battlefield or terror scenes in forensic
      investigations where trace level analysis is required.

PMID- 30297236
TI  - Chromatography of mono- and disaccharides on granulated pellets of hydrophobic
      zeolites.
AB  - The chromatographic response of sugars at granulated zeolite pellets in
      preparative scale liquid chromatography is analyzed with respect to the
      distribution equilibrium and mass transfer. In contrast to hydrophilic FAU type
      zeolites their hydrophobic dealuminated counterpart, used here, can separate
      disaccharides the retention of which can strongly exceed those of the monosugars.
      The retention is correlated with data of batch adsorption studies from the
      literature. Whereas the retention decreases with increasing temperature, the peak
      sharpness shows the opposite trend. The effective mass resistance is calculated
      for a series of mono- and disaccharides. It increases with the capacity factor.
      The diffusion coefficient of the trehalulose disaccharide is restricted by a
      factor of about 2 in the macropores and by a factor of more than 104 in the
      micropores.

PMID- 30297237
TI  - [Dermatofibrosarcoma: Management].
AB  - Dematofibrosarcoma protuberans (DFSP) are very rare (1 to 4 incident cases per
      million of inhabitants). The local spreading of DFSP is underestimated. The
      histological diagnosis is challenging but we now know a specific marker
      (translocation t(17;22)(q22;q13) (COL1A1;PDGFB)). The risk of metastatic relapse
      is low (and related to fibrosarcoma component); the risk of local relapse depends
      on the quality of surgery. Management of localized DFSP is based on large
      resection with meticulous analysis of margins (with or without Mohs
      microsurgery). Advanced stages not amenable to surgery or metastatic DFSP (with
      presence of COL1A1;PDGFB) are best treated with imatinib. Locally advanced DFSP
      potentially amenable to curative intent surgery could be treated with imatinib as
      neo-adjuvant treatment. The management of these tumours requires
      multidisciplinary expertise.

PMID- 30297239
TI  - The smoker's paradox: Not an argument against quitting smoking after acute
      coronary syndrome.

PMID- 30297238
TI  - Retraction notice to "Experimental and numerical study for seawater intrusion
      remediation in heterogeneous coastal aquifer " [Volume 198, Part 1, 1 August
      2017, Pages 221-232].

PMID- 30297240
TI  - Obstruction predicts worse long-term outcomes in stage III colon cancer: A
      secondary analysis of the N0147 trial.
AB  - BACKGROUND: Patients with colon cancer often present with obstruction. Large
      series have reported obstruction among the high-risk features, yet prospective
      data on its specific prognostic influence are lacking. We hypothesized that
      obstruction is an independent risk factor for poor prognosis in patients with
      stage III colon cancer. METHODS: N0147 was a trial conducted between 2004 and
      2009 that randomly assigned patients with stage III colon cancer to adjuvant
      regimens of folinic acid (leucovorin calcium), fluorouracil, and oxaliplatin or
      fluorouracil, leucovorin, and irinotecan, with or without cetuximab. Patient
      level data from the control chemotherapy-only arms were obtained. Patient, tumor,
      and treatment characteristics were abstracted. Disease-free survival and overall
      survival were estimated by the Kaplan-Meier method. Proportions were compared by
      chi2 and Fisher exact tests. Univariable and multivariable survival analyses were
      performed using Cox proportional hazards models. RESULTS: Of 1,543 patients with
      stage III colon cancer, 250 (16.2%) presented with obstruction. Patients with
      obstruction were equally likely to complete 12 cycles of adjuvant chemotherapy
      (75.9% vs 77.1%, P = .6). With median follow-up time of 30.9 months among
      survivors, five-year overall survival and disease-free survival were worse among
      patients with obstruction (overall survival 67.7% vs 78.0%, P < .001; disease
      free survival 53.9% vs 67.0%, P < .0001). On multivariable analysis, obstruction
      remained significantly associated with worse survival after adjusting for T
      stage, N stage, performance status, age, sex, histologic grade, and body mass
      index (overall survival hazard ratio 1.57, 95% confidence interval 1.12-2.20, P =
      .001; disease-free survival 1.52, 95% confidence interval 1.18-1.95, P < .001).
      CONCLUSION: In this prospectively followed cohort of patients with stage III
      colon cancer treated with adjuvant chemotherapy, obstruction was associated with
      recurrence and worse survival. Moreover, this effect was independent of T and N
      stage and histologic grade. These results suggest that obstruction should be
      incorporated into novel risk-stratification models.

PMID- 30297241
TI  - Influence of lung donor agonal and warm ischemic times on early mortality:
      Analyses from the ISHLT DCD Lung Transplant Registry.
AB  - BACKGROUND: In this study we aimed to assess the impact of agonal time and warm
      ischemic time on early survival in Category III donation-after-circulatory-death
      (DCD) donor lung transplants (LTxs) using data reported to the International
      Society for Heart and Lung Transplantation (ISHLT) DCD Lung Transplant Registry.
      METHODS: In this retrospective study, data were analyzed for 507 DCD LTxs done
      between January 2005 and June 2015. DCD lung donor agonal time (defined as
      withdrawal of life support to cessation of cardiac output) and warm ischemic time
      (WIT; defined as donor systolic blood pressure <50mm Hg to cold pulmonary artery
      flush) were divided into 3 clinical timing categories (<30 minutes, 30 to 60
      minutes, >60 minutes) and 3 tertiles. Univariate analysis was undertaken for all
      categorizations, and Day 30/Day 365 Kaplan-Meier survival rates were calculated
      and compared. Multivariable analysis included Cox proportional hazards regression
      models to estimate hazard of 365-day mortality. RESULTS: Four hundred sixty-five
      and 301 DCD LTxs had data to analyze in the agonal and warm ischemic time groups,
      respectively. Day 30 and Day 365 post-transplant survival overall were 96% and
      90%, respectively, and not statistically different according to agonal or WIT
      category or tertile. CONCLUSIONS: Current experience with DCD Category III LTx
      does not show a relationship between the duration of donor agonal phase or warm
      ischemic time up to 60 minutes and early survival. These results suggest the true
      limits of clinical DCD allograft warm ischemic times may not yet be reached.
      Global variations in clinical DCD practice are apparent. Continued accurate
      recording and analyses of DCD processes is warranted.

PMID- 30297242
TI  - Immunotherapy is Here to Stay: A New Treatment Paradigm in Lung Cancer.

PMID- 30297243
TI  - Silicone Thorax: Another Complication of Breast Prosthesis Rupture.

PMID- 30297244
TI  - Muscle Dysfunction in Chronic Obstructive Pulmonary Disease: Latest Developments.

PMID- 30297245
TI  - Speciation and the City.
AB  - Many outstanding questions about speciation are difficult to test empirically
      because of a lack of suitable study systems. Here, we highlight studies of
      evolutionary ecology in urban environments to argue that cities provide ideal
      conditions that can be leveraged to study the speciation process. Considering
      general findings from these studies, we discuss the mechanisms of speciation that
      are likely to occur in cities. We also discuss fundamental questions about
      speciation that urban environments are uniquely suited to address, such as those
      about the earliest stages of divergence or the role of phenotypic plasticity. We
      conclude that the study of contemporary speciation in urban environments has
      promise to facilitate discoveries about the process of speciation as it occurs in
      the Anthropocene.

PMID- 30297246
TI  - Electronic Patient-Reported Outcomes: Semi-Automated Data Collection in the
      Interventional Radiology Clinic.
AB  - INTRODUCTION: Patient-reported outcomes are important for clinical research and
      will likely be used in the near future as a metric for physician reimbursement.
      This study aims to evaluate the implementation of an electronic data collection
      system for deep vein thrombosis and lymphedema quality-of-life (QOL)
      questionnaires in a tertiary care interventional radiology practice. METHODS: A
      single provider's clinic patients were automatically e-mailed validated
      questionnaires 1 week before their appointments. If not completed via e-mail, the
      questionnaire was administered on an electronic tablet in clinic by a research
      coordinator. Patients were also sent postprocedure questionnaires. RESULTS: In
      all, 106 patients visited the clinic for a pre-intervention venous consultation.
      Of them, 96% (n = 102 of 106) completed the pre-intervention questionnaire: 48%
      (n = 47 of 98) via e-mail and 52% (n = 51 of 98) via tablet. Of the patients who
      had procedures and were sent questionnaires, 49% (n = 26 of 53) were seen in
      person. Of the postprocedure in-person clinic patients, 76% (n = 20 of 26)
      completed the questionnaire via e-mail, and the remainder with the tablet in
      clinic. Twenty-seven of the 53 (51%) patients did not return for follow-up and
      instead were sent an electronic questionnaire as their only source of follow-up,
      of which 74% (n = 20 of 27) complied. CONCLUSION: After an initial introduction
      to electronic QOL reporting, patients were more likely to complete the
      questionnaires remotely for their follow-up appointment. A semi-automated
      electronic QOL system allows physicians to collect patient outcome data even in
      the absence of a clinic visit.

PMID- 30297247
TI  - Massive cardiac and pulmonary thrombi after cardiac surgery.

PMID- 30297248
TI  - Appropriateness of ordering serum angiotensin-converting enzyme during renin
      angiotensin-aldosterone system inhibitor therapy.

PMID- 30297249
TI  - Papulopustules and paronychia in a lung carcinoma.

PMID- 30297250
TI  - Association between heat stroke and ischemic heart disease: A national
      longitudinal cohort study in Taiwan.
AB  - The purpose of this study is to determine the relationship between heat stroke
      and ischemic heart disease (IHD), in a nationwide population using a longitudinal
      approach. We retrospectively examined the data from the National Health Insurance
      Research Database (NHIRD) in Taiwan, for patients examined between 2000 and 2013.
      In total, 628 patients with a heat stroke episode were enrolled and matched with
      1256 patients without any history of a heat stroke episode by propensity score
      matching at a ratio of 1:2. The mean follow-up years of the heat stroke group was
      11.89 years and the mean follow up of the control group was 11.51 years. An
      association between heat stroke episodes and IHD (log-rank p < .001) was found in
      a univariate cox regression analysis. After multivariate adjustment, age,
      comorbidities (hypertension, diabetes, stroke), and lower insurance premiums were
      associated with IHD events in patients who had a heat stroke. IHD was
      independently associated with heat stroke following cox multivariate regression
      analysis and patients with a heat stroke episode had a higher incidence of IHD
      events compared to those without any heat stroke episode (2598.41/105 person
      years vs. 1286.14/105 person-years, adjusted hazard ratio 3.527, 95% CI: 2.078
      4.032, p < .001). The onset of IHD in patients who suffered a heat stroke was
      earlier than in those without a heat stroke episode (2.08 +/- 3.45 vs. 3.61 +/-
      3.25 years, p < .001). In conclusion, clinicians should be aware about evaluating
      the IHD risk following a heat stroke episode in a patient.

PMID- 30297251
TI  - Mortality and morbidity due to exposure to particulate matter related to drying
      Urmia Lake in the NW Iran.

PMID- 30297252
TI  - Analysis of predictive response scores to treatment with ursodeoxycholic acid in
      patients with primary biliary cholangitis.
AB  - BACKGROUND AND OBJECTIVES: Primary biliary cholangitis (PBC) is an autoimmune
      disease that affects the small bile ducts. The only treatments currently approved
      in our country are ursodeoxycholic acid (UDCA) and obeticholic acid. Different
      indices evaluate the response after one year of treatment. The aim of our study
      was to evaluate the different predictive scores and prognostic factors of
      response to UDCA. MATERIAL AND METHODS: Retrospective single-centre study in
      which clinical and analytical data of patients diagnosed with PBC were collected
      from January 1987 to December 2015. The response after one year of treatment was
      evaluated using the different response scores and their concordance degree using
      the Kappa index. The area under the receiver operating characteristic curve
      (AUROC) was calculated to determine the predictive capacity of the scores.
      Likewise, the prognostic factors of response to treatment were analysed. RESULTS:
      We included 153 patients. The bivariate analysis showed a statistically
      significant relationship between the initial high levels of alkaline phosphatase
      and cholesterol and the poor response to treatment. The best AUROC was in Paris-I
      score (0.81). The concordance between the different scores was low. The GLOBE
      score was valid to evaluate the prognosis. CONCLUSION: Basal alkaline phosphatase
      and cholesterol were predictors of poor outcome. The best predictive qualitative
      score in our cohort patients was Paris-I. There was a poor concordance between
      the different predictive scores. GLOBE score is valid to evaluate prognosis.

PMID- 30297253
TI  - Isolated involuntary weight loss: Epidemiology and predictive factors of
      malignancy.
AB  - BACKGROUND AND OBJECTIVES: The aims of the study were to analyse the
      epidemiology, prognostic and predictive factors of malignant disease on isolated
      involuntary weight loss (IIWL) and to know the effectiveness of the quick
      diagnosis unit in the evaluation of the process. MATERIAL AND METHODS:
      Prospective observational study realised from 2006 to 2015 of all patients who
      were evaluated with IIWL in the quick diagnosis unit. Demographic, clinical,
      diagnostic and evolutive variables were analysed. Through the analysis of
      logistic regression, predictive factors of malignant disease and prognostic
      factors were identified. RESULTS: Of the 533 registered patients, 55.1% were>=65
      years old. The diagnostics were: non-neoplastic organic disorders in 214 patients
      (40.2%), psychiatric disorders in 144 (27%), cancer in 81 (15.2%) and unknown
      cause in 94 (17.6%). In 66.7% of the patients with cancer, there was an increase
      of serum tumour markers (STM). Being over 60 (OR: 2.57; 95% CI: 1.27-5.77; P=.01)
      %), male (OR: 3.23; 95% CI: 1.52-6.87; P=0.002), increase of an STM (OR: 2.38;
      95% CI: 1.17-4.8; P=0.016) and more than one STM (OR: 6.51; 95% CI: 2.62-16.13;
      P=0.000) were identified as predictive factors of malignancy. Mortality was
      14.2%; the diagnosis of cancer (OR: 47.61; 95% CI: 20.76-109.19; P=0.000) was
      identified as a prognostic factor. CONCLUSIONS: IIWL is a clinical syndrome that
      requires a study with a sequential protocol and follow-up. STM were identified as
      predictive factors of malignancy.

PMID- 30297255
TI  - Correction to Lancet Glob Health 2018; 6: e1077-86.

PMID- 30297256
TI  - New Insights Into the Use of Cardiac Magnetic Resonance Imaging to Guide Decision
      Making in Atrial Fibrillation Management.
AB  - Recent advances in cardiac magnetic resonance (CMR) imaging acquisition
      techniques have enabled the visualization of thin atrial myocardium with high
      temporal and spatial resolution and have the potential to shift atrial
      fibrillation (AF) management paradigms. Late gadolinium-enhancement (LGE)-CMR can
      noninvasively identify atrial arrhythmogenic scar substrates and has been shown
      to spatially correlate with low-voltage areas. Immediately after ablation, a
      combination of native T1-weighted, LGE, and T2-weighted imaging can assess
      ablation lesions and localize reversible edema, whereas late after ablation, LGE
      CMR can visualize irreversible fibrosis and detect large ablation gaps. Tissue
      tracking on cine-CMR can be used to characterize the impact of ablation and AF
      related remodelling on atrial structure and contractile function. Increased
      burden of "native" LGE and lower left atrial function at baseline are associated
      with worse procedural outcomes, and identification of patients with the greatest
      fibrotic extent may improve patient selection for AF ablation procedures or
      identify a subset of patients for whom pulmonary vein isolation alone is unlikely
      to be beneficial. Left atrial appendage morphology and left atrial sphericity
      index may provide additional prognostic information in AF ablations. A suggested
      approach for patients with extensive fibrosis includes substrate modification in
      addition to pulmonary vein isolation. Another approach involves virtual
      electrophysiological simulation of AF, localization of computationally derived AF
      drivers, and determination of optimal ablation targets for persistent AF
      suppression. Finally, both LGE-CMR and cine-CMR have offered invaluable insights
      into AF-related stroke mechanisms and may enhance available prediction models
      that guide anticoagulation therapy.

PMID- 30297254
TI  - Medical errors communication. Ethical and medicolegal issues.

PMID- 30297257
TI  - Metaphyseal sleeves in revision total knee arthroplasty: Minimum seven-year
      follow-up study.
AB  - BACKGROUND: Metal metaphyseal sleeves are an option for reconstruction as well as
      enhancing fixation in managing challenging bone defects in revision knee
      replacement. We report our results of revision knee replacement using metaphyseal
      sleeves with a minimum of seven years of follow-up. METHODS: The records of 103
      patients (104 knees) who underwent revision knee replacement using metaphyseal
      sleeves in our centre were evaluated. The follow-up included clinical assessment,
      functional scores and radiologic assessment. RESULTS: The mean age of patients
      was 74.7 (tange 58-92) years. Mean follow-up was 95.7 (range, 88-115) months.
      From the original cohort, 15 (14%) patients had died from unrelated causes.
      During the follow-up period, there were 23 (22.1%) re-revisions. Indications for
      re-revision was aseptic loosening in seven (6.7%), stiffness in four (3.8%),
      infection in five (4.8%), instability in three (2.8%) and persistent pain in two
      (1.9%) patients. For aseptic loosening, the average time for re-revisions was
      56.6 months (range 25 to 84). Radiographically, all unrevised sleeves were well
      fixed, without any evidence of loosening. Oxford knee score in patients without
      re-revisions was 28.5 (range four to 48). CONCLUSION: At mid-term follow-up,
      metaphyseal sleeves demonstrate durable clinical results and radiographic
      fixation.

PMID- 30297258
TI  - Estimation of non-shivering thermogenesis and cold-induced nutrient oxidation
      rates: Impact of method for data selection and analysis.
AB  - BACKGROUND & AIMS: Since the discovery of active brown adipose tissue in human
      adults, non-shivering cold-induced thermogenesis (CIT) has been regarded as a
      promising tool to combat obesity. However, there is a lack of consensus regarding
      the method of choice to analyze indirect calorimetry data from a CIT study. We
      analyzed the impact of methods for data selection and methods for data analysis
      on measures of cold-induced energy expenditure (EE) and nutrient oxidation rates.
      METHODS: Forty-four young healthy adults (22.1 +/- 2.1 years old, 25.6 +/- 5.2
      kg/m2, 29 women) participated in the study. Resting metabolic rate (RMR), cold
      induced thermogenesis (CIT), and cold-induced nutrient oxidation rates were
      estimated by indirect calorimetry under fasting conditions during 1 h of cold
      exposure combining air conditioning (19.5-20  degrees C) and a water perfused
      cooling vest set at a temperature of 4  degrees C above the individual shivering
      threshold. We applied three methods for data selection: (i) time intervals every
      5 min (5min-TI), (ii) the most stable 5-min period of every forth part of the
      cold exposure (5min-SS-4P), and (iii) the most stable 5-min period of every half
      part of the cold exposure (5min-SS-2P). Lately we applied two methods for data
      analysis: (i) area under the curve as a percentage of the baseline RMR (AUC) and;
      (ii) the difference between EE at the end of the cold exposure and baseline RMR
      (Last-RMR). RESULTS: Mean overall CIT estimation ranged from 11.6 +/- 10.0 to
      20.1 +/- 17.2 %RMR depending on the methods for data selection and analysis used.
      Regarding methods for data selection, 5min-SS-2P did not allow to observe
      physiologically relevant phenomena (e.g. metabolic shift in fuel oxidation; P =
      0.547) due to a lack of resolution. The 5min-TI and 5min-SS-4P methods for data
      selection seemed to be accurate enough to observe physiologically relevant
      phenomena (all P < 0.014), but not comparable for estimating over-all CIT and
      cold-induced nutrient oxidation rates (P < 0.01). Regarding methods for data
      analysis, the AUC seemed to be less affected for data artefacts and to be more
      representative in participants with a non-stable energy expenditure during cold
      exposure. CONCLUSIONS: The methods for data selection and analysis can have a
      profound impact on CIT and cold-induced nutrient oxidation rates estimations, and
      therefore, it is mandatory to unify it across scientific community to allow inter
      study comparisons. Based on our findings, 5min-TI should be considered the method
      of choice to study dynamics (i.e. changes across time) of CIT and cold-induced
      nutrient oxidation rates, while 5min-SS-4P and AUC should be the method of choice
      when computing CIT and cold-induced nutrient oxidation rates as a single value.

PMID- 30297259
TI  - Unusual Late Presentation of a Rare Complex Aorto-Pulmonary Malformation
      Diagnosed on Computed Tomography Angiography.

PMID- 30297260
TI  - Esophageal Perforation After Transesophageal Echocardiography During Cardiac
      Surgery and Delayed Diagnosis.

PMID- 30297261
TI  - [Structuring and supporting specialist training in general practice: Evaluation
      of a Hesse-wide mentoring program for doctors].
AB  - INTRODUCTION: Due to the growing shortage of general practitioners (GPs),
      solutions are being sought to improve the structure and attraction of specialist
      training in general practice. In 2012, the Competence Center for Specialist
      Training in General Practice was set up in the federal state of Hesse, Germany,
      in order to provide a seminar- and mentoring program to complement standard
      specialist training. The present paper examines whether the mentoring program,
      which was based on needs assessment, supports doctors in training (DiT) to become
      specialists in general practice. METHODS: A mixed-methods design was used for the
      evaluation of the mentoring program. The pilot cohort monitored in this study was
      surveyed using a guideline-based interview. The cohort consisted of the first
      cohort of participants in the Specialist Training Academy (n=21), which was
      divided into two mentoring groups. Responses were evaluated with the help of the
      MAXQDA 11 program and qualitative content analysis to structure content.
      Furthermore, all 16 group meetings were assessed by means of evaluation sheets
      (n=132) and analyzed descriptively using the statistics program SPSS (IBM
      statistics, Version 20). RESULTS: Of the 21 DiTs of the total sample that took
      part in the interviews, two-thirds of the surveyed mentees were female (71.4 %).
      The mentoring and seminar programs encouraged the mentees in their decision for
      and their identification with specialist training in general practice and helped
      them overcome any doubts about their choice. The decisive factors in the
      mentoring process were interacting with like-minded people, discussing
      organizational questions and having a fixed contact person in case of questions
      and doubts. The evaluation sheets made it clear that the mentees regarded the
      mentoring as supportive (99.3 % positive). Compared to the other mentoring group,
      participants in the one group felt they were better supported by mentoring, found
      the interaction with other DiTs more helpful, the interaction between mentors and
      the group exactly right, and the topics they discussed more relevant. CONCLUSION:
      The provided mentoring program fulfilled the expectations of the DiTs in general
      practice. Combined with the Specialist Training Academy's seminar program, the
      two programs complement each other and are an important step towards making
      specialist training in general practice more attractive.

PMID- 30297262
TI  - Five decades of orofacial cleft management and research in Brazil.

PMID- 30297264
TI  - Factors Affecting Oncologic Outcomes of 90Y Radioembolization of Heavily Pre
      Treated Patients With Colon Cancer Liver Metastases.
AB  - INTRODUCTION: The purpose of this study was to identify predictors of overall
      (OS) and liver progression-free survival (LPFS) following Yttrium-90
      radioembolization (RAE) of heavily pretreated patients with colorectal cancer
      liver metastases (CLM), as well as to create and validate a predictive nomogram
      for OS. MATERIALS AND METHODS: Metabolic, anatomic, laboratory, pathologic,
      genetic, primary disease, and procedure-related factors, as well as pre- and post
      RAE therapies in 103 patients with CLM treated with RAE from September 15, 2009
      to March 21, 2017 were analyzed. LPFS was defined by Response Evaluation Criteria
      In Solid Tumors 1.1 and European Organization for Research and Treatment of
      Cancer criteria. Prognosticators of OS and LPFS were selected using univariate
      Cox regression, adjusted for clustering and competing risk analysis (for LPFS),
      and subsequently tested in multivariate analysis (MVA). The nomogram was built
      using R statistical software and internally validated using bootstrap resampling.
      RESULTS: Patients received RAE at a median of 30.9 months (range, 3.4-161.7
      months) after detection of CLM. The median OS and LPFS were 11.3 months (95%
      confidence interval, 7.9-15.1 months) and 4 months (95% confidence interval, 3.3
      4.8 months), respectively. Of the 40 parameters tested, 6 were independently
      associated with OS in MVA. These baseline parameters included number of
      extrahepatic disease sites (P < .001), carcinoembryonic antigen (P < .001),
      albumin (P = .005), alanine aminotransferase level (P < .001), tumor
      differentiation level (P < .001), and the sum of the 2 largest tumor diameters (P
      < .001). The 1-year OS of patients with total points of < 25 versus > 80 was 90%
      and 10%, respectively. Bootstrap resampling showed good discrimination (optimism
      corrected c-index = 0.745) and calibration (mean absolute prediction error =
      0.299) of the nomogram. Only baseline maximum standardized uptake value was
      significant in MVA for LPFS prediction (P < .001; SHR = 1.06). CONCLUSION: The
      developed nomogram included 6 pre-RAE parameters and provided good prediction of
      survival post-RAE in heavily pretreated patients. Baseline maximum standardized
      uptake value was the single significant predictor of LPFS.

PMID- 30297263
TI  - Effects of Adjuvant Chemotherapy on Cognitive Function of Patients With Early
      stage Colorectal Cancer.
AB  - PURPOSE: Chemotherapy-related cognitive impairment can occur in cancer survivors
      after treatment, especially those patients who have undergone chemotherapy for
      breast cancer. The frequency and to what extent such toxicity develops in
      colorectal cancer (CRC) survivors is unknown. The present prospective study
      evaluated the effects of adjuvant chemotherapy on the cognitive performance of
      patients with localized CRC compared with a control group who had not undergone
      chemotherapy. PATIENTS AND METHODS: Consecutive patients with localized stage II
      and III CRC completed neuropsychological assessments, self-reported cognitive
      complaint questionnaires, and depressive symptom evaluations before starting
      fluoropyrimidine-based adjuvant chemotherapy and after 12 months. Blood was
      collected for apolipoprotein E genotyping. Diffusion tensor imaging data were
      acquired from a subset of participants at both evaluation points. RESULTS: From
      December 2012 to December 2014, 137 patients were approached and 85 were
      included. Of these 85 patients, 49 had undergone chemotherapy and 26 had not, in
      accordance with the standard recommendations for adjuvant therapy for CRC. The
      mean age was 62.5 +/- 9.4 years, 60% were men, and the mean educational
      attainment was 7.6 +/- 3.7 years. No difference was found in the global composite
      score (P = .38), attention (P = .84), or memory (P = .97) between the 2 groups
      during the follow-up period (mean +/- standard deviation, 375 +/- 29 days).
      However, a statistically significant difference was found for executive function
      after adjustment for age, sex, education, and depressive symptoms at baseline
      (beta -1.80; 95% confidence interval, -3.50 to -0.11; P = .04), suggesting worse
      performance for the chemotherapy group. For the 32 patients who had undergone
      magnetic resonance imaging, tract-based spatial statistics did not show voxelwise
      significant differences in structural brain connectivity at baseline or during
      follow-up. Apolipoprotein E polymorphisms were not predictive of cognitive
      dysfunction. CONCLUSION: Patients with CRC who received adjuvant 5-fluorouracil
      with or without oxaliplatin presented with a decline in executive function after
      12 months compared with patients with localized disease who had not received
      chemotherapy.

PMID- 30297265
TI  - Association Between Primary Payer Status and Survival in Patients With Stage III
      Colon Cancer: An National Cancer Database Analysis.
AB  - BACKGROUND: Colon cancer is the third most frequent cancer diagnosis, and primary
      payer status has been shown to be associated with treatment modalities and
      survival in cancer patients. The goal of our study was to determine the between
      insurance differences in survival in patients with clinical stage III colon
      cancer using data from the National Cancer Database (NCDB). MATERIALS AND
      METHODS: We identified 130,998 patients with clinical stage III colon cancer in
      the NCDB diagnosed from 2004 to 2012. Kaplan-Meier curves and multivariable Cox
      regression models were used to determine the association between insurance status
      and survival. RESULTS: Patients with private insurance plans were 28%, 30%, and
      16% less likely to die than were uninsured patients, Medicaid recipients, and
      Medicare beneficiaries, respectively. Medicare patients were 14% were less likely
      to die compared with uninsured patients. Patients receiving chemotherapy were, on
      average, 65% less likely to die compared with the patients not receiving
      chemotherapy. CONCLUSION: Private insurance and a greater socioeconomic status
      were associated with increased patient survival compared with other insurance
      plans or the lack of insurance. Future research should continue to unravel how
      socioeconomic status and insurance status contribute to the quality of care and
      survival of oncologic patients.

PMID- 30297266
TI  - Physical Activity Intensity and Cardiovascular Disease Prevention-From the
      Seguimiento Universidad de Navarra Study.
AB  - The association between the intensity of physical activity and the incidence of
      cardiovascular diseases (CVD), irrespective of energy expenditure (EE), requires
      further study. Our objective is to examine this relationship using data from a
      large Spanish cohort. The Seguimiento Universidad de Navarra cohort is formed of
      university graduates recruited from March 1999 to October 2015. We included
      18,737 adults free of CVD (mean age 38 years, 61% women), with a median follow-up
      of 10.3 years. We estimated the average intensity of leisure time physical
      activity (LTPA) using a validated questionnaire. We classified respondents into 3
      groups: Inactive, <6 average metabolic equivalents (METs) and >=6 average METs.
      We used Cox proportional hazards models adjusted by the EE in LTPA (MET-h/week)
      and other confounding factors, to examine this association. During 1,72,299
      person-years of follow-up, we registered 127 cases of CVD (myocardial infarction,
      stroke, and death due to cardiovascular causes). The adjusted hazard ratio for
      CVD was 0.76 (95% CI 0.48 to 1.21) in the lower intensity group, and 0.31 (95% CI
      0.12 to 0.79) in the higher intensity group, compared with the inactive, with a
      linear trend (p = 0.03). In conclusion, given the same level of EE, those
      respondents engaged in higher intensity LTPA, had a lower risk of CVD.

PMID- 30297267
TI  - Temporal Trends in Utilization of Right-Sided Heart Catheterization Among
      Percutaneous Ventricular Assist Device Recipients in Acute Myocardial Infarction
      Complicated by Cardiogenic Shock.
AB  - Percutaneous ventricular assist devices (PVAD) have been used at an increasing
      rate in patients with acute myocardial infarction complicated by cardiogenic
      shock (AMI-CS). Recent evidence has demonstrated that use of invasive hemodynamic
      monitoring with right-sided heart catheterization (RHC) was associated with
      improved survival in recipients of PVAD in AMI-CS. We sought to examine the
      utilization of RHC in patients receiving PVAD in AMI-CS. We queried the
      Nationwide Inpatient Sample database from 2008 to 2014 and identified patients
      using ICD-9-CM codes for AMI-CS (410, 785.51), PVAD (37.68), and RHC (37.21,
      37.23). Temporal trends were analyzed using Cochrane Armitage test. In 5,925
      patients who were treated with PVAD for AMI-CS, 1,691 (28.5%) underwent RHC. The
      mean (SD) age was 63.9 (12.3) years; majority were males (72.8%) and white
      (63.3%). Patients receiving RHC had higher baseline burden of co-morbidities,
      Charlson Co-morbidity Index >=2 (56.1%). From 2008 to 2014, there was decrease in
      the utilization of RHC in patients receiving PVAD from 40.4% to 29.8% (ptrend =
      0.0005). Mortality decreased in patients who received RHC (56% to 42.6%, ptrend =
      0.005), whereas mortality increased in patients without RHC (44.4% to 48.4%,
      ptrend = 0.001). In conclusion, in patients who present with AMI-CS and were
      treated with PVAD, there was a progressive decline in the utilization of RHC,
      despite a temporal decrease in mortality in patients receiving RHC. Novel
      strategies should be explored to increase the use of RHC in this high-risk
      patient population.

PMID- 30297268
TI  - Meta-Analysis Comparing Outcomes of Drug Eluting Stents Versus Single and
      Multiarterial Coronary Artery Bypass Grafting.
AB  - Relative benefits of coronary artery bypass (CABG) using single and multiple
      arterial grafting (SAG, MAG) and drug eluting stent (DES) in multivessel coronary
      disease remain uncertain. We compared SAG, MAG, and DES in a pairwise and network
      meta-analysis. Randomized trials and adjusted observational studies comparing
      CABG versus DES were included (primary end point: long-term mortality; secondary
      end points: operative mortality, perioperative stroke, and follow-up repeated
      revascularization [RR]). Studies with >=1.7 arterial grafts and/or patient were
      classified as MAG. Bayesian network meta-analyses and random-model pairwise meta
      analyses were performed. A total of 53,239 patients (8 randomized, 17
      observational studies) were included (26,306 DES; 26,933 CABG). In pairwise
      comparison (mean follow-up: 5.42 years), CABG (MAG + SAG) was associated with
      lower long-term mortality (incident rate ratio [IRR] 0.77, 95% confidence
      interval [CI] 0.66 to 0.90), lower RR (IRR 0.37, 95% CI 0.27 to 0.51), increased
      perioperative stroke (odds ratio [OR] 3.18, 95% CI 1.70 to 5.97), and similar
      operative mortality (OR 1.04, 95% CI 0.64 to 1.70) compared with DES. There was a
      nonsignificant trend toward lower long-term mortality for studies with higher
      mean number of arterial grafts. In network meta-analyses, compared with DES, MAG
      was associated with lower long-term mortality (IRR 0.72, 95% credible interval
      [CrI] 0.57 to 0.92) and late RR (IRR 0.32, 95% CrI 0.21 to 0.49), SAG was
      associated with lower long-term mortality and RR (IRR 0.80, 95% CrI 0.66 to 0.97
      and IRR 0.42, 95% CrI 0.29 to 0.61, respectively). In conclusion, CABG was
      associated with reduced 5-year mortality and need for RR compared with DES. MAG
      was ranked as the best treatment for the primary and all secondary outcomes.

PMID- 30297270
TI  - Investigating blood eosinophil count thresholds in patients with COPD.

PMID- 30297269
TI  - Allergen Extracts for In Vivo Diagnosis and Treatment of Allergy: Is There a
      Future?
AB  - Today, in vivo allergy diagnosis and allergen-specific immunotherapy (AIT) are
      still based on allergen extracts obtained from natural allergen sources. Several
      studies analyzing the composition of natural allergen extracts have shown severe
      problems regarding their quality such as the presence of undefined nonallergenic
      materials, contaminants as well as high variabilities regarding contents and
      biological activity of individual allergens. Despite the increasing availability
      of sophisticated analytical technologies, these problems cannot be overcome
      because they are inherent to allergen sources and methods of extract production.
      For in vitro allergy diagnosis problems related to natural allergen extracts have
      been largely overcome by the implementation of recombinant allergen molecules
      that are defined regarding purity and biological activity. However, no such
      advances have been made for allergen preparations to be used in vivo for
      diagnosis and therapy. No clinical studies have been performed for allergen
      extracts available for in vivo allergy diagnosis that document safety,
      sensitivity, and specificity of the products. Only for very few therapeutic
      allergen extracts state-of-the-art clinical studies have been performed that
      provide evidence for safety and efficacy. In this article, we discuss problems
      related to the inconsistent quality of products based on natural allergen
      extracts and share our observations that most of the products available for in
      vivo diagnosis and AIT do not meet the international standards for medicinal
      products. We argue that a replacement of natural allergen extracts by defined
      recombinantly produced allergen molecules and/or mixtures thereof may be the only
      way to guarantee the supply of clinicians with state-of-the-art medicinal
      products for in vivo diagnosis and treatment of allergic patients in the future.

PMID- 30297271
TI  - United to end tuberculosis.

PMID- 30297272
TI  - No. 367-2019 Canadian Guideline for Physical Activity throughout Pregnancy.
AB  - OBJECTIVE: The objective is to provide guidance for pregnant women, and obstetric
      care and exercise professionals, on prenatal physical activity. OUTCOMES: The
      outcomes evaluated were maternal, fetal, or neonatal morbidity or fetal mortality
      during and following pregnancy. EVIDENCE: Literature was retrieved through
      searches of Medline, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews,
      Cochrane Central Register of Controlled Trials, Scopus and Web of Science Core
      Collection, CINAHL Plus with Full-text, Child Development & Adolescent Studies,
      ERIC, Sport Discus, ClinicalTrials.gov, and the Trip Database from database
      inception up to January 6, 2017. Primary studies of any design were eligible,
      except case studies. Results were limited to English, Spanish, or French language
      materials. Articles related to maternal physical activity during pregnancy
      reporting on maternal, fetal, or neonatal morbidity or fetal mortality were
      eligible for inclusion. The quality of evidence was rated using the Grading of
      Recommendations Assessment, Development, and Evaluation (GRADE) methodology.
      VALUES: The Guidelines Consensus Panel solicited feedback from end-users
      (obstetric care providers, exercise professionals, researchers, policy
      organizations, and pregnant and postpartum women). The development of this
      guideline followed the Appraisal of Guidelines for Research Evaluation (AGREE) II
      instrument. BENEFITS, HARMS, AND COSTS: The benefits of prenatal physical
      activity are moderate, and no harms were identified; therefore, the difference
      between desirable and undesirable consequences (net benefit) is expected to be
      moderate. The majority of stakeholders and end-users indicated that following
      these recommendations would be feasible, acceptable, and equitable. Following
      these recommendations is likely to require minimal resources from both individual
      and health systems perspectives. PREAMBLE: This guideline provide evidence-based
      recommendations regarding physical activity throughout pregnancy in the promotion
      of maternal, fetal, and neonatal health. In the absence of contraindications (see
      later for a detailed list), following this guideline is associated with: (1)
      fewer newborn complications (i.e., large for gestational age); and (2) maternal
      health benefits (i.e., decreased risk of preeclampsia, gestational hypertension,
      gestational diabetes, Caesarean section, instrumental delivery, urinary
      incontinence, excessive gestational weight gain, and depression; improved blood
      glucose; decreased total gestational weight gain; and decreased severity of
      depressive symptoms and lumbopelvic pain). Physical activity is not associated
      with miscarriage, stillbirth, neonatal death, preterm birth, preterm/prelabour
      rupture of membranes, neonatal hypoglycemia, low birth weight, birth defects,
      induction of labour, or birth complications. In general, more physical activity
      (frequency, duration, and/or volume) is associated with greater benefits.
      However, evidence was not identified regarding the safety or additional benefit
      of exercising at levels significantly above the recommendations. Prenatal
      physical activity should be considered a front-line therapy for reducing the risk
      of pregnancy complications and enhancing maternal physical and mental health. For
      pregnant women not currently meeting this guideline, a progressive adjustment
      toward them is recommended. Previously active women may continue physical
      activity throughout pregnancy. Women may need to modify physical activity as
      pregnancy progresses. There may be periods when following the guideline is not
      possible due to fatigue and/or discomforts of pregnancy; women are encouraged to
      do what they can and to return to following the recommendations when they are
      able. This guideline were informed by an extensive systematic review of the
      literature, expert opinion, end-user consultation and considerations of
      feasibility, acceptability, costs, and equity. RECOMMENDATIONS: The specific
      recommendations in this 2019 Canadian Guideline for Physical Activity Throughout
      Pregnancy are provided below with corresponding statements indicating the quality
      of the evidence informing the recommendations and the strength of the
      recommendations (explanations follow). CONTRAINDICATIONS: All pregnant women can
      participate in physical activity throughout pregnancy with the exception of those
      who have contraindications (listed below). Women with absolute contraindications
      may continue their usual activities of daily living but should not participate in
      more strenuous activities. Women with relative contraindications should discuss
      the advantages and disadvantages of moderate-to-vigorous intensity physical
      activity with their obstetric care provider prior to participation. Absolute
      contraindications to exercise are the following: Relative contraindications to
      exercise are the following: STRENGTH OF THE RECOMMENDATIONS: The GRADE system was
      utilized to grade the strength of the recommendations. Recommendations are rated
      as strong or weak based on the: (1) balance between benefits and harms; (2)
      overall quality of the evidence; (3) importance of outcomes (i.e., values and
      preferences of pregnant women); (4) use of resources (i.e., cost); (5) impact on
      health equity; (6) feasibility, and (7) acceptability. Strong recommendation:
      Most or all pregnant women will be best served by the recommended course of
      action. Weak recommendation: Not all pregnant women will be best served by the
      recommended course of action; there is a need to consider other factors such as
      the individual's circumstances, preferences, values, resources available, or
      setting. Consultation with an obstetric care provider may assist in decision
      making. QUALITY OF THE EVIDENCE: The quality of the evidence refers to the level
      of confidence in the evidence and ranges from very low to high. High quality: The
      Guideline Consensus Panel is very confident that the estimated effect of physical
      activity on the health outcome is close to the true effect. Moderate quality: The
      Guideline Consensus Panel is moderately confident in the estimated effect of
      physical activity on the health outcome; the estimate of the effect is likely to
      be close to the true effect, but there is a possibility that it is substantially
      different. Low quality: The Guideline Consensus Panel's confidence in the
      estimated effect of physical activity on the health outcome is limited; the
      estimate of the effect may be substantially different from the true effect. Very
      low quality: The Guideline Consensus Panel has very little confidence in the
      estimated effect of physical activity on the health outcome; the estimate of the
      effect is likely to be substantially different from the true effect. aThis was a
      weak recommendation because the quality of evidence was low, and the net benefit
      between women who were physically active and those who were not was small. bThis
      was a strong recommendation because, despite low quality evidence supporting
      physical activity during pregnancy for women categorized as overweight or obese,
      there was evidence from randomized controlled trials demonstrating an improvement
      in gestational weight gain and blood glucose. cModerate-intensity physical
      activity is intense enough to noticeably increase heart rate; a person can talk
      but not sing during activities of this intensity. Examples of moderate-intensity
      physical activity include brisk walking, water aerobics, stationary cycling
      (moderate effort), resistance training, carrying moderate loads, and household
      chores (e.g., gardening, washing windows). dThis was a weak recommendation
      because urinary incontinence was was not rated as a "critical" outcome and the
      evidence was low quality. eThis was a weak recommendation because: (1) the
      quality of evidence was very low; and (2) although harms were investigated there
      was limited available information to inform the balance of benefits and harms.
      This recommendation was primarily based on expert opinion.

PMID- 30297273
TI  - RNA sequencing (RNA-Seq) and its application in ovarian cancer.
AB  - Despite the surgical and chemotherapeutic advances over the past few decades,
      ovarian cancer remains the leading cause of gynecological cancer-related
      mortality. The absence of biomarkers in early detection and the development of
      drug resistance are principal causes of treatment failure in ovarian cancer.
      Recent progress in RNA sequencing (RNA-Seq) with Next Generation Sequencing
      technology has expanded the understanding of the molecular pathogenesis of
      ovarian cancer. As compared to previous hybridization-based microarray and Sanger
      sequence-based methods, RNA-Seq provides multiple layers of resolutions and
      transcriptome complexity, with less background noise and a broader dynamic range
      of RNA expression. Beyond quantifying gene expression, the data generated by RNA
      Seq accelerates the identification of alternatively spliced genes, fusion genes,
      mutations/SNPs, allele-specific expression, novel transcripts and non-coding
      RNAs. RNA-Seq has been successfully applied in ovarian cancer research for
      earlier detection, ascertaining pathological origin, and defining the aberrant
      genes and dysregulated molecular pathways across patient groups. This review
      outlines the distinct advantages of RNA-Seq compared to other transcriptomics
      methods and its recent applications in ovarian cancer.

PMID- 30297274
TI  - Reply to: "Incidence of grade 3-4 liver injury under immune checkpoints
      inhibitors: A retrospective study".

PMID- 30297275
TI  - Role of a pre-operative radiological scoring system in determining resectability
      for potentially resectable hilar cholangiocarcinoma.
AB  - AIMS: Cholangiocarcinoma is a rare cancer arising from the biliary tree. Case
      series indicate that 25-40% of all borderline resectable primary tumours are
      potentially resectable. The Memorial Sloane Kettering System (MSKCC) stratifies
      patients for resectability by longitudinal and radial extension of the hilar
      tumour. The Bismuth-Corlette system describes the longitudinal extension of the
      tumour within the biliary duct system. We sought to validate and, if possible,
      augment these two scores within an independent validation cohort. METHODS:
      Patients diagnosed with hilar cholangiocarcinoma between January 2009 and
      December 2016 were analysed from a prospectively held database. Patients with
      distal cholangiocarcinoma, peripheral cholangiocarcinoma and gallbladder cancer
      were excluded. Comparison of surgical findings to pre-operative radiological
      imaging was undertaken at the time of surgery. RESULTS: The validation cohort was
      formed of 198 patients, of which, 55 (27.8%) patients underwent resection.
      Logistic regression analyses identified that BC score, MSKCC score, age at
      diagnosis and left artery involvement were all significant independent
      predictor's univariately. BC score explained 28% of the variability in
      resectability compared to 26% explained by MSKCC. In combination, the model
      consisting of BC score, age at diagnosis and left artery involvement explained
      39% of variability in resectability compared to the 34% explained same model
      including MSKCC score instead of BC score. CONCLUSION: In this cohort an
      augmented BC score, incorporating left hepatic artery involvement, is more
      discriminative in predicting resectability than the current MSKCC system.

PMID- 30297277
TI  - Prophylaxis of Infective Endocarditis in Dentistry: Analysis of the Situation
      After Almost a Decade of Clinical Practice Guidelines. Response.

PMID- 30297276
TI  - Spanish Heart Transplant Registry. 29th Official Report of the Spanish Society of
      Cardiology Working Group on Heart Failure.
AB  - INTRODUCTION AND OBJECTIVES: The present report updates the characteristics and
      results of heart transplantation in Spain, mainly focused in the 2008-2017
      period. METHODS: We describe the recipient and donor characteristics, surgical
      procedures, and outcomes of heart transplants performed in 2017. The 2017 data
      were compared with those obtained from 2008 to 2016. RESULTS: A total of 304
      cardiac transplants were performed in 2017. Between 1984 and 2017, 8173
      procedures were performed, 2689 of them after 2008. Significant temporal trends
      were observed in recipient characteristics (lower pulmonary vascular resistance,
      lower use of mechanical ventilation, and a higher percentage of diabetic patients
      and those with previous cardiac surgery), donor characteristics (older donor age
      and a higher percentage of female donors and those with a prior cardiac arrest)
      and procedures (lower ischemia time). In 2017, 27% of patients were transplanted
      after undergoing mechanical ventricular assistance (P <.001 for trend). In the
      last decade, there was a trend to better survival. CONCLUSIONS: Around 300
      transplants per year were performed in Spain in the last decade. There was a
      significant increase in the use of pretransplant mechanical circulatory support
      and a trend to improved survival.

PMID- 30297279
TI  - Spanish Cardiac Catheterization and Coronary Intervention Registry. 27th Official
      Report of the Spanish Society of Cardiology Working Group on Cardiac
      Catheterization and Interventional Cardiology (1990-2017).
AB  - INTRODUCTION AND OBJECTIVES: To present the annual report of the Working Group on
      Cardiac Catheterization and Interventional Cardiology on the activity data for
      2017. METHODS: Data were voluntarily provided by Spanish centers with a
      catheterization laboratory. The information was introduced online and was
      analyzed by the Steering Committee of the Working Group on Cardiac
      Catheterization and Interventional Cardiology. RESULTS: In 2017, data were
      reported by 107 hospitals, of which 82 are public. A total of 154 218 diagnostic
      procedures (138 448 coronary angiograms) were performed (2.2% increase vs 2016).
      The use of intracoronary diagnostic techniques significantly increased,
      especially that of pressure wire (23.2% vs 2016, n=7003). In 2017, the number of
      percutaneous coronary interventions rose to 70 928 (3.2% increase), of which 21
      395 interventional procedures were performed in the acute myocardial infarction
      setting. A total of 105 529 stents were implanted, of which 90.3% were drug
      eluting stents (6% increase). Radial access was used in 85.7% of diagnostic
      procedures and in 88.4% of interventional procedures. The number of transcatheter
      aortic valve implantations continued to increase (28.2% increase, n=2821), as did
      the number of left atrial appendage closures (14.8% increase, n=582) and
      percutaneous mitral valve repair procedures (14.1% increase, n=270). CONCLUSIONS:
      Diagnostic and therapeutic procedures in acute myocardial infarction increased in
      2017. The use of the radial approach and drug-eluting stents also increased in
      therapeutic procedures. The number of structural procedures rose significantly
      compared with previous years.

PMID- 30297278
TI  - Baseline Risk Stratification of Patients Older Than 75 Years With Infarction and
      Cardiogenic Shock Undergoing Primary Angioplasty.
AB  - BACKGROUND AND OBJECTIVES: Patients older than 75 years with ST-segment elevation
      myocardial infarction undergoing primary angioplasty in cardiogenic shock have
      high mortality. Identification of preprocedural predictors of short- and long
      term mortality could be useful to guide decision-making and further
      interventions. METHODS: We analyzed a nationwide registry of primary angioplasty
      in the elderly (ESTROFA MI+75) comprising 3576 patients. The characteristics and
      outcomes of the subgroup of patients in cardiogenic shock were analyzed to
      identify associated factors and prognostic predictors in order to derive a
      baseline risk prediction score for 1-year mortality. The score was validated in
      an independent cohort. RESULTS: A total of 332 patients were included. Baseline
      independent predictors of mortality were anterior myocardial infarction (HR 2.8,
      95%CI, 1.4-6.0 P=.005), ejection fraction<40% (HR 2.3, 95%CI, 1.14-4.50 P=.018),
      and time from symptom onset to angioplasty >6hours (HR 3.2, 95%CI, 1.6-7.5;
      P=.001). A score was designed that included these predictive factors (score "6
      ANT-40"). Survival at 1 year was 54.5% for patients with score 0, 32.3% for score
      1, 27.4% for score 2 and 17% for score 3 (P=.004, c-statistic 0.70). The score
      was validated in an independent cohort of 124 patients, showing 1-year survival
      rates of 64.5%, 40.0%, 28.9%, and 22.2%, respectively (P=.008, c-statistic 0.68).
      CONCLUSIONS: A preprocedural score based on 3 simple clinical variables (anterior
      location, ejection fraction<40%, and delay time >6 hours) may be used to estimate
      survival after primary angioplasty in elderly patients with cardiogenic shock and
      to guide preinterventional decision-making.

PMID- 30297280
TI  - Impact of body mass index on outcomes after thoracic trauma-A matched-triplet
      analysis of the TraumaRegister DGU(r).
AB  - INTRODUCTION: Chest trauma and obesity are both associated with increased risks
      for respiratory complications (e.g. hypoxia, hypercarbia, pneumonia), which are
      frequent causes of posttraumatic morbidity and mortality. However, as there is
      only limited and inconsistent evidence, the aim of our study was to analyse the
      effect of body mass index (BMI) on patient outcomes after thoracic trauma.
      PATIENTS AND METHODS: We screened 50.519 patients entered in TraumaRegister
      DGU(r), between 2004-2009, when the BMI was part of the standardized dataset.
      After matching for injury patterns and severity of trauma we performed a matched
      tripled analysis with regard to the BMI (group 1: <25.0 kg/m2; group 2: 25.0-29.9
      kg/m2; group 3: >30.0 kg/m2). Data are shown as percentages and mean values with
      standard deviation. RESULTS: The matching process yielded a cohort of 828
      patients with serious blunt thoracic trauma, evenly distributed over the 3 BMI
      groups (276 triplets). BMI did not have an impact on the need for prehospital or
      emergency department interventions. There was a trend towards more liberal use of
      whole-body-CT scanning with increasing BMI (group 1: 68.8%; group 2: 73.2%; group
      3: 75.0%). Additional abdominal injuries were more common in normal weight
      patients (Group 1: 28.3%; Group 2: 14.9%; Group 3: 17.8%). Obesity (BMI > 30.0
      kg/m2) had a significant impact on the duration of mechanical ventilation (in
      days; group 1: 6.5 (9.4); group 2: 6.4 (8.9); group 3: 9.1 (14.4); p = 0.002),
      ICU days (in days; group 1: 11.5 (11.5); group 2: 10.9 (9.6); group 3: 14.1
      (16.7); p = 0.005) and hospital length of stay (in days; group 1: 27.8 (19.3);
      group 2: 27.4 (19.2); group 3: 32.2 (25.9); p = 0.009). There were no significant
      differences regarding overall mortality (group 1: 3.6%; group 2: 1.8%; group 3:
      4.0%; p = 0.26). CONCLUSIONS: Obesity has a negative impact on outcomes after
      blunt chest trauma, as it is associated with prolonged duration of mechanical
      ventilation, ICU and hospital length of stay. Mortality did not seem to be
      affected, yet, further research is required to confirm these results in a larger
      cohort.

PMID- 30297281
TI  - Structure-activity relationships of pyrazole-4-carbodithioates as antibacterials
      against methicillin-resistant Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of serious
      hospital-acquired infections and is responsible for significant morbidity and
      mortality in residential care facilities. New agents against MRSA are needed to
      combat rising resistance to current antibiotics. We recently reported 5-hydroxy-3
      methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC) as a new bacteriostatic agent
      against MRSA that appears to act via a novel mechanism. Here, twenty nine analogs
      of HMPC were synthesized, their anti-MRSA structure-activity relationships
      evaluated and selectivity versus human HKC-8 cells determined. Minimum inhibitory
      concentrations (MIC) ranged from 0.5 to 64 MUg/mL and up to 16-fold selectivity
      was achieved. The 4-carbodithioate function was found to be essential for
      activity but non-specific reactivity was ruled out as a contributor to
      antibacterial action. The study supports further work aimed at elucidating the
      molecular targets of this interesting new class of anti-MRSA agents.

PMID- 30297282
TI  - Improved potency and reduced toxicity of the antifungal peptoid AEC5 through
      submonomer modification.
AB  - As proteolytically stable peptidomimetics, peptoids could serve as antifungal
      agents to supplement a therapeutic field wrought with toxicity issues. We report
      the improvement of an antifungal peptoid, AEC5, through an iterative structure
      activity relationship study. A sarcosine scan was used to first identify the most
      pharmacophorically important peptoid building blocks of AEC5, followed by
      sequential optimization of each building block. The optimized antifungal peptoid
      from this study, beta-5, has improved potency towards Cryptococcus neoformans and
      decreased toxicity towards mammalian cells. For example, the selectivity ratio
      for C. neoformans over mammalian fibroblasts was improved from 8 for AEC5 to 37
      for beta-5.

PMID- 30297283
TI  - Identification of steroidal derivatives inhibiting the transformations of
      allopregnanolone and estradiol by 17beta-hydroxysteroid dehydrogenase type 10.
AB  - 17beta-Hydroxysteroid dehydrogenase type 10 (17beta-HSD10) is a mitochondrial
      enzyme known for its potential role in Alzheimer's Disease (AD). 17beta-HSD10, by
      its oxidative activity, could decrease the concentration of two important
      neurosteroids, allopregnanolone (ALLOP) and 17beta-estradiol (E2), respectively
      preventing their neurogenesis and neuroprotective effects. Since the inhibition
      of 17beta-HSD10 could lead to a new treatment for AD, we developed two biological
      assays using labeled ALLOP or E2 as substrates to measure the inhibitory activity
      of compounds against pure 17beta-HSD10 protein. After the optimization of
      different parameters (time, concentration of enzyme, substrate and cofactor),
      analogs of the first reported steroidal inhibitor of 17beta-HSD10 in intact cells
      were screened to determine their inhibitory potency for the ALLOP or the E2
      oxidation. One compound, androstane derivative 5, possesses the best dual
      inhibition against both transformations (ALLOP, IC50 = 235 MUM and E2, IC50 = 610
      MUM). Some compounds are dual inhibitors to a lesser extent, and others seem
      selective for one of the transformations in particular. By developing two
      reliable assays and by identifying a first generation of steroidal inhibitors of
      pure 17beta-HSD10, this preliminary study opens the door to new and more potent
      inhibitors.

PMID- 30297284
TI  - Discovery of a potent, low-absorbable sodium-dependent glucose cotransporter 1
      (SGLT1) inhibitor (TP0438836) for the treatment of type 2 diabetes.
AB  - The design and synthesis of a novel class of low-absorbable SGLT1 inhibitors are
      described. To achieve low absorption in the new series, we performed an
      optimization study based on a strategy to increase TPSA. Fortunately, the
      optimization of an aglycon moiety and a side chain of the distal aglycon moiety
      led to the identification of compound 30b as a potent and low-absorbable SGLT1
      inhibitor. Compound 30b showed a desirable PK profile in Sprague-Dawley (SD) rats
      and a favorable glucose-lowering effect in diabetic rats.

PMID- 30297285
TI  - Design, synthesis and evaluation of curcumin-based fluorescent probes to detect
      Abeta fibrils.
AB  - Amyloid beta fibrillation is an early event in Alzheimer's disease, so its
      detection is important to understand its roles in Alzheimer's disease. Curcumin,
      which has poor water solubility, has been reported to have many pharmacological
      activities including potent anti-amyloid beta fibril activity in Alzheimer's
      disease. In this study, we found that curcumin analogues with the fluorescence
      property instead of non-inhibition of amyloid beta fibrils. The development of
      new curcumin analogue, Me-CUR (9), as fluorescent switchable probe to detect
      amyloid beta fibrils is described. Me-CUR (9) shows excellent fluorescence,
      especially higher than ThT (4), in the presence of amyloid beta fibrils. These
      results suggest that Me-CUR (9) can become a useful in vitro amyloid fluorescence
      sensor for diagnosis of Alzheimer's disease.

PMID- 30297286
TI  - Occipital Dermal Sinus: The Tip of the Iceberg.

PMID- 30297287
TI  - Airway Microbiome and Development of Bronchopulmonary Dysplasia in Preterm
      Infants: A Systematic Review.
AB  - OBJECTIVES: To summarize evidence regarding microbial dysbiosis of the airway
      associated with bronchopulmonary dysplasia (BPD) and to explore heterogeneity
      among studies. STUDY DESIGN: We included studies that evaluated the airway
      microbiome in preterm infants who developed BPD using culture-independent
      molecular techniques and reported alpha- and beta-diversity metrics and microbial
      profiles. RESULTS: The 6 included studies had substantial clinical and
      methodological heterogeneity. Most studies reported the presence of an airway
      microbiome early after birth and an evolution in the first weeks of life with
      increasing bacterial loads. The early airway microbiome was dominated by
      Staphylococcus and Ureaplasma spp. Two studies reported differences in alpha- and
      beta- diversity indices in preterm infants with BPD compared with those who did
      not develop BPD. Increased microbial community turnover, changes in the relative
      abundance of Proteobacteria and Firmicutes, and decreased Lactobacilli were
      reported with BPD progression. Most included infants were born by cesarean
      delivery, and a majority were exposed to postnatal antibiotics. No data regarding
      feeding human milk or correlations with the development of gut microbiota (gut
      lung axis) were available. CONCLUSIONS: Microbial dysbiosis may be associated
      with BPD progression and severity, and further study of microbiome optimization
      in preterm infants at risk for BPD is warranted.

PMID- 30297288
TI  - Assessment of Body Mass Index in Infancy: It Is Time to Revise Our Guidelines.

PMID- 30297289
TI  - Predicting Maintenance of Any Breastfeeding from Exclusive Breastfeeding
      Duration: A Replication Study.
AB  - OBJECTIVES: To predict the duration of any breastfeeding using the duration of
      exclusive breastfeeding in a socioeconomically heterogeneous sample of mothers
      using receiver operator characteristic (ROC) analysis. STUDY DESIGN: The Mother
      Baby Health Survey, a birth certificate-linked cross-sectional survey was sent at
      4-5 months postpartum to a stratified random sample of socioeconomically and
      racially diverse women in upstate New York; 797 mothers who initiated exclusive
      breastfeeding were included in this study. Split-sample validation was employed;
      eligible subjects were divided into training or test samples at random (80% and
      20%, respectively). ROC curves were constructed using the training sample and
      optimal exclusive breastfeeding duration thresholds were tested using the
      remaining test sample. Logistic regression using the training sample provided
      estimates of the predictive ability (sensitivity, specificity, positive
      predictive value) of thresholds in both unadjusted and adjusted analyses
      (covariates: age, education, parity, marital status, and race). RESULTS: The ROC
      analysis in this sample demonstrated that 9 weeks of exclusivity was required for
      maintenance of breastfeeding at 3 months, and 14.9 weeks of exclusivity was
      required for maintenance at 20 weeks. Unadjusted and adjusted models yielded
      similar results; women who exclusively breastfed for at least 9 weeks had 2.2
      times the risk (95% CI 1.7-2.8) of maintaining any breastfeeding at 3 months.
      CONCLUSIONS: These results are similar to our previous results, from a less
      diverse cohort, and support that these thresholds may be useful in clinical
      settings for helping mothers achieve breastfeeding duration goals.

PMID- 30297290
TI  - Predominance of Rotavirus G8P[8] in a City in Chile, a Country Without Rotavirus
      Vaccination.
AB  - Rotavirus G8P[8] infection has been common in Africa, but rare in the Americas.
      Among 23 rotavirus episodes observed during 18 months of surveillance of 100
      families in Chile, 11 (48%) were identified as G8P[8]. Genotypes from these
      strains shared >99% identity with rotavirus sequences described in Asia, and may
      be misclassified as mixed G8/G12.

PMID- 30297291
TI  - Screening for Toxic Stress Risk Factors at Well-Child Visits: The Addressing
      Social Key Questions for Health Study.
AB  - OBJECTIVES: To determine the prevalence of and demographic characteristics
      associated with toxic stress risk factors by universal screening, the impact of
      screening on referral rates to community resources, and the feasibility and
      acceptability of screening in a medical home setting. STUDY DESIGN: We developed
      the Addressing Social Key Questions for Health Questionnaire, a 13-question
      screen of adverse childhood experiences (ACEs) and unmet social needs.
      Parents/guardians of children 0-17 years of age received this questionnaire at
      well-child visits at 4 academic clinics from August 1, 2016 to February 28, 2017.
      Providers reviewed the tool and referred to community resources as needed. A
      subset of families completed demographic and satisfaction surveys. Prevalence of
      ACEs and unmet social needs, community referral rates at 1 site with available
      data, and family acceptability data were collected. Analyses included frequency
      distributions, chi2 tests, and Poisson regression. RESULTS: Of 2569 families
      completing an Addressing Social Key Questions for Health Questionnaire, 49%
      reported >=1 stressor; 6% had >=1 ACE; 47% had >=1 unmet social need. At 1 site,
      community referral rates increased from 2.0% to 13.3% (P < .0001) after screening
      implementation. Risk factors for having a stressor include male sex and African
      American or Hispanic race. 86% of 446 families want clinics to continue
      screening. CONCLUSIONS: Universal screening for toxic stress risk factors in
      pediatric primary care improved identification and management of family needs.
      Screening was feasible and acceptable to families. Prevalence of unmet social
      needs but not ACEs was comparable with prior studies. Further evaluation and
      modification of the screening protocol is needed to increase screening and
      identification.

PMID- 30297293
TI  - Birth Hospitalization Costs and Days of Care for Mothers and Neonates in
      California, 2009-2011.
AB  - OBJECTIVE: To provide population-based estimates of the hospital-related costs of
      maternal and newborn care, and how these vary by gestational age and birth
      weight. STUDY DESIGN: We conducted a retrospective analysis of 2009-2011
      California in-hospital deliveries at nonfederal hospitals with the infant and
      maternal discharge data successfully (96%) linked to birth certificates. Cost-to
      charge ratios were used to estimate costs from charges. Physician hospital
      payments were estimated by mean diagnosis related group-specific reimbursement
      and costs were adjusted for inflation to December 2017 values. After exclusions
      for incomplete or missing data, the final sample was 1 265 212. RESULTS: The mean
      maternal costs for all in-hospital deliveries was $8204, increasing to $13 154
      for late preterm (32-36 weeks) and $22 702 for very preterm (<32 weeks) mothers.
      The mean cost for all newborns was $6389: $2433 for term infants, $22 102 for
      late preterm, $223 931 for very preterm infants, and $317 982 for extremely
      preterm infants (<28 weeks). Preterm infants were 8.1% of cases but incurred
      60.9% of costs; for very preterm and extremely preterm infants, these shares were
      1.0% and 36.5%, and 0.4% and 20.0%, respectively. Overall, mothers incurred 56%
      of the total costs during the delivery hospitalization. CONCLUSIONS: Both
      maternal and neonatal costs are skewed, with this being much more pronounced for
      infants. Preterm birth is much more expensive than term delivery, with the
      additional costs predominately incurred by the infants. The small share of
      infants who require extensive stays in neonatal intensive care incur a large
      share of neonatal costs and these costs have increased over time.

PMID- 30297292
TI  - Factors Associated with Adverse Outcomes among Febrile Young Infants with
      Invasive Bacterial Infections.
AB  - OBJECTIVE: To determine factors associated with adverse outcomes among febrile
      young infants with invasive bacterial infections (IBIs) (ie, bacteremia and/or
      bacterial meningitis). STUDY DESIGN: Multicenter, retrospective cohort study
      (July 2011-June 2016) of febrile infants <=60 days of age with pathogenic
      bacterial growth in blood and/or cerebrospinal fluid. Subjects were identified by
      query of local microbiology laboratory and/or electronic medical record systems,
      and clinical data were extracted by medical record review. Mixed-effect logistic
      regression was employed to determine clinical factors associated with 30-day
      adverse outcomes, which were defined as death, neurologic sequelae, mechanical
      ventilation, or vasoactive medication receipt. RESULTS: Three hundred fifty
      infants met inclusion criteria; 279 (79.7%) with bacteremia without meningitis
      and 71 (20.3%) with bacterial meningitis. Forty-two (12.0%) infants had a 30-day
      adverse outcome: 29 of 71 (40.8%) with bacterial meningitis vs 13 of 279 (4.7%)
      with bacteremia without meningitis (36.2% difference, 95% CI 25.1%-48.0%; P <
      .001). On adjusted analysis, bacterial meningitis (aOR 16.3, 95% CI 6.5-41.0; P <
      .001), prematurity (aOR 7.1, 95% CI 2.6-19.7; P < .001), and ill appearance (aOR
      3.8, 95% CI 1.6-9.1; P = .002) were associated with adverse outcomes. Among
      infants who were born at term, not ill appearing, and had bacteremia without
      meningitis, only 2 of 184 (1.1%) had adverse outcomes, and there were no deaths.
      CONCLUSIONS: Among febrile infants <=60 days old with IBI, prematurity, ill
      appearance, and bacterial meningitis (vs bacteremia without meningitis) were
      associated with adverse outcomes. These factors can inform clinical decision
      making for febrile young infants with IBI.

PMID- 30297294
TI  - The Prevalence of Rib Fractures Incidentally Identified by Chest Radiograph among
      Infants and Toddlers.
AB  - OBJECTIVES: To determine the prevalence of incidental rib fractures identified by
      chest radiograph (CXR) obtained for indications unrelated to accidental trauma or
      nonaccidental trauma (NAT), and describe the histories associated with cases of
      incidental rib fractures and their proposed etiologies. It is hypothesized that
      incidental rib fractures are rare and alternative explanations for rib fractures
      occasionally used in a medico-legal context such as minor accidental trauma,
      undiagnosed medical conditions, and transient metabolic bone disturbances are
      unlikely to be the etiology of incidental rib fractures. STUDY DESIGN: A
      retrospective chart review of sequential CXRs of children ages 0 to <2 years was
      conducted from January 1, 2011 to October 31, 2016. CXRs were obtained in the
      emergency department, general pediatric or intensive care units, or outpatient
      pediatric clinics. Data collected included demographics, CXR indication and
      findings, history of cardiopulmonary resuscitation, laboratory and additional
      imaging results, and incidental rib fracture descriptions and proposed
      etiologies. RESULTS: A total of 7530 patients underwent 9720 CXRs associated with
      unique clinical encounters. Five CXRs had incidental rib fractures identified,
      making the prevalence of CXRs with incidental rib fractures in this cohort <0.1%.
      Of 5 identified incidental cases, mean age was 3.6 months, 3 were concerning for
      NAT, 1 was confirmed NAT, and 1 had radiographic findings consistent with
      osteopenia of prematurity. CONCLUSIONS: Identification of incidental rib fracture
      on CXR is rare. When detected in the absence of corresponding trauma history
      and/or objective laboratory or radiographic metabolic abnormalities, work-up for
      NAT should be pursued.

PMID- 30297295
TI  - Effects of Prone Sleeping on Cerebral Oxygenation in Preterm Infants.
AB  - OBJECTIVE: To determine the effect of prone sleeping on cerebral oxygenation in
      preterm infants in the neonatal intensive care unit. STUDY DESIGN: Preterm
      infants, divided into extremely preterm (gestational age 24-28 weeks; n = 23) and
      very preterm (gestational age 29-34 weeks; n = 33) groups, were studied weekly
      until discharge in prone and supine positions during active and quiet sleep.
      Cerebral tissue oxygenation index (TOI) and arterial oxygen saturation (SaO2)
      were recorded. Cerebral fractional tissue extraction (CFOE) was calculated as
      CFOE = (SaO2 - TOI)/SaO2. RESULTS: In extremely preterm infants, CFOE increased
      modestly in the prone position in both sleep states at age 1 week, in no change
      in TOI despite higher SaO2. In contrast, the very preterm infants did not have
      position-related differences in CFOE until the fifth week of life. In the very
      preterm infants, TOI decreased and CFOE increased with active sleep compared with
      quiet sleep and with increasing postnatal age. CONCLUSION: At 1 week of age,
      prone sleeping increased CFOE in extremely preterm infants, suggesting reduced
      cerebral blood flow. Our findings reveal important physiological insights in
      clinically stable preterm infants. Further studies are needed to verify our
      findings in unstable preterm infants regarding the potential risk of cerebral
      injury in the prone sleeping position in early postnatal life.

PMID- 30297296
TI  - Evaluation of the rs3088442 G>A SLC22A3 Gene Polymorphism and the Role of
      microRNA 147 in Groups of Adult Pakistani Populations With Type 2 Diabetes in
      Response to Metformin.
AB  - OBJECTIVES: Type 2 diabetes is a complex genetic disorder, and a large number of
      genetic polymorphisms may be involved in its pathogenesis. Pharmacologically,
      type 2 diabetes can be treated with 9 different approved classes of drugs, but
      metformin is suggested as the first line of therapy, followed by sulfonylureas.
      METHODS: This was a case-control study consisting of 300 metformin responders and
      300 metformin nonresponders in patients with type 2 diabetes and 300 healthy
      Pakistani subjects. Genotyping of the SLC22A3 G>A polymorphism was performed by
      allele-specific polymerase chain reaction (PCR) for microRNA 147 expression; real
      time polymerase chain reaction was used, and expressional analysis of SLC22A3 was
      done by semiquantitative polymerase chain reaction. RESULTS: GA and AA genotypes
      were highly significantly associated with the drug treatments when compared with
      controls. A statistically significant difference was observed in the distribution
      of the SLC22A3 A allele between healthy subjects and patients with type 2
      diabetes. When odds ratios were adjusted for glycated hemoglobin levels and
      postprandial and fasting blood glucose levels, our findings showed that the
      overexpression of allele A of the rs3088442 G>A variant may act as a protective
      allele and is associated with the clinical response to metformin. microRNA 147
      expression was found to be increased in patients who were metformin responders
      compared with the nonresponder group and controls. mRNA expression of SLC22A3 was
      significantly reduced in patients taking metformin as compared to other groups.
      CONCLUSIONS: These results suggested that the SLC22A3 rs3088442 at position 2282
      A allele may confer metformin clinical responses in patients with type 2 diabetes
      in the Pakistani population. Overexpression of microRNA 147 is associated with a
      downward expression of the SLC22A3 gene in patients who have type 2 diabetes.

PMID- 30297297
TI  - Intercellular Adhesion Molecule-1 Lys469Glu Polymorphism, Systemic Redox
      Homeostasis and Gestational Diabetes Mellitus in Pregnant Women.
AB  - OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1) plays an important role in
      endothelial function. Hyperglycemia-induced impaired redox status is 1 of the
      well-known pathophysiologic characteristics of gestational diabetes mellitus
      (GDM), and it plays a crucial role in the causes of disease. Our aim was to
      clarify any possible relationship between the ICAM-1 Lys469Glu polymorphism and
      systemic redox status in women with and without GDM. Also, we investigated
      whether this polymorphism could be associated with a change for better or worse
      as evidenced by clinical and redox biomarkers. METHODS: The ICAM-1 polymorphism
      statuses of 89 pregnant women without GDM and 53 pregnant women with GDM were
      found. Stratifying patients based on GDM and polymorphism status, we investigated
      various redox homeostasis markers. The independent t test was used. RESULTS:
      Significantly higher systemic oxidative damage and diminished antioxidant defense
      were found in pregnant women with GDM. Also, results showed that whether pregnant
      women were carrying the Lys469Glu polymorphism or not did not seem to be
      associated with significant differences, as evidenced by comparable systemic
      oxidative damage. CONCLUSIONS: Although no significant difference was observed
      between genotypes, the oxidative damage observed in patients with GDM warrants
      earlier screening and management in the light of new evidence.

PMID- 30297298
TI  - Storytelling to Support Disease Self-Management by Adults With Type 2 Diabetes.
AB  - OBJECTIVES: This pilot project aimed to examine the acceptability and feasibility
      of a group storytelling intervention to support self-management among adults
      living with type 2 diabetes. METHODS: Two waves of a single-arm storytelling
      intervention, consisting of 8 sessions at a community health centre, were
      delivered to 8 adults with type 2 diabetes. Diabetes educators facilitated each
      session, in which patients shared stories about diabetes-self-management topics
      of their choice. Focus groups with both patients and facilitators explored the
      feasibility and acceptability of the sessions. External raters assessed the
      fidelity of the intervention's implementation. RESULTS: Overarching themes
      describe the acceptability and feasibility of the intervention: 1) the
      facilitation of patient self-direction, group cohesion, collective learning and
      support; 2) roles of facilitator educator, and peer learner; 3) the
      intervention's customization to patients' preferences. The sessions were
      delivered with high fidelity (averaging 84.4%). CONCLUSIONS: Informal group
      storytelling enables patients to discuss, understand and give personal meaning to
      the information that was exchanged, and facilitates educators' better
      understanding of patients' concerns and gaps in knowledge and how-to strategies
      that can inform their practice. The group storytelling intervention is acceptable
      to patients and educators and can be delivered with high fidelity. Further
      research into effective patient recruitment methods and evaluation of the
      intervention's impact on diabetes self-management is required.

PMID- 30297299
TI  - In reply to "Mechanical thrombectomy in acute ischemic stroke, knowing our
      results".

PMID- 30297300
TI  - Impact of support agreement between municipalities and convenience store chain
      companies on store staff's support activities for older adults.
AB  - In the continuously aging society, private sectors are expected to play a role in
      older adult care. Implementing an agreement between municipalities and private
      sectors is one of the key mechanisms for encouraging private sectors to
      participate in supporting older adults. The study's aim was to evaluate whether
      the support agreement has promoted support activities by convenience store staff
      for older adults. A retrospective observational study was conducted between 2013
      and 2016 using data from a nationwide survey of convenience stores. The
      municipality-level matching produced 168 municipality pairs, with 2242
      convenience stores that entered into a support agreement with municipalities from
      2014 to 2015, and 2141 stores without such an agreement. Convenience store-level
      logistic regression analysis evaluated the impact of the agreement on staff
      activities. The analysis showed that some staff activities increased
      significantly with the support agreement, such as corresponding or collaborating
      with community support centers (AOR = 3.40; 95% CI: 2.22 to 5.26), participating
      in role-playing programs for older adult care (AOR = 2.05; 95% CI: 1.01 to 4.26),
      and attending dementia support lectures (AOR = 18.21; 95% CI: 8.27 to 45.34).
      Emergency protection for older adults did not increase with the support
      agreement. The results suggest that the support agreement positively influenced
      some convenience store staff's support activities for older adults.

PMID- 30297301
TI  - 'I just want to be able to make a choice': Results from citizen deliberations
      about mammography screening in Ontario, Canada.
AB  - Despite Canada's long history with mammography screening, little is known about
      citizens' perspectives about mammography and how best to support women to make
      informed choices about screening. To address this gap, a series of four citizen
      deliberation events were held in 2015-16 in Ontario, a Canadian province with an
      organized population-based breast screening program in place since 1990. Forty
      nine individuals participated in four citizen panels, each comprising an
      information session highlighting the evidence about mammography, and large- and
      small-group deliberations about approaches to support informed decision making
      for screening. Following their engagement with the research evidence about
      mammography, participants expressed concern about their lack of full awareness of
      the risks and benefits and a strong desire for choice when it comes to screening.
      To support informed choice, mammography programs need to reflect the values of
      information sharing, trust and transparency, financial accountability, and allow
      for personal interactions and shared decision-making. Citizens are looking for
      balanced information about the risks and benefits of screening presented in an
      easy to understand, comprehensive, and transparent manner. Primary health care
      providers and organized screening programs are important sources of information
      about mammography and must be vigilant in their efforts to support informed
      decision-making in this area by ensuring that the information materials they are
      using are balanced and reflect current evidence.

PMID- 30297302
TI  - Growth of diabetes drug expenditure decomposed-A nationwide analysis.
AB  - OBJECTIVES: The aim of this study was to quantify different factors underlying
      the growth of diabetes drug expenditure in Finland. METHODS: Data representing
      purchases of antidiabetic agents between 2003 and 2015 were extracted from a
      nationwide prescription register. By using Fisher's Ideal Indexes, the per capita
      expenditure growth for both insulins and non-insulin antidiabetic agents was
      decomposed into six different determinants: purchase volume, purchase size,
      switches between therapeutic classes, switches within therapeutic classes, unit
      costs and switches to generic alternatives. RESULTS: Between 2003 and 2015, the
      per capita expenditure on insulins increased by ?8.64 and on non-insulins by
      ?13.73. For insulins, holding other factors constant, change in the number of
      purchases represented a ?4.67 increase in expenditure, change in the size of
      purchases a ?4.33 increase and switches between therapeutic classes a ?4.07
      increase. For non-insulins, change in the number of purchases represented a
      ?10.22 increase in expenditure and switches between therapeutic classes, a ?10.17
      increase. Changes in purchase size increased the non-insulin per capita
      expenditure by ?1.48. For both insulins and non-insulins, changes in prices and
      product level switches had decreasing effects on expenditures. CONCLUSIONS: The
      main drivers of the growth in diabetes drug expenditure were volume growth and
      switches to newer and more expensive drugs. Price changes, however, had a
      decreasing effect on the overall diabetes drug expenditure.

PMID- 30297303
TI  - Structure-activity profiling of alkaloid natural product pharmacophores against a
      Schistosoma serotonin receptor.
AB  - Serotonin (5-HT) is an important regulator of numerous aspects of flatworm
      biology, ranging from neuromuscular function to sexual maturation and egg laying.
      In the parasitic blood fluke Schistosoma mansoni, 5-HT targets several G-protein
      coupled receptors (GPCRs), one of which has been demonstrated to couple to cAMP
      and regulate parasite movement. This receptor, Sm.5HTRL, has been successfully co
      expressed in mammalian cells alongside a luminescent cAMP-biosensor, enabling
      pharmacological profiling for candidate anti-schistosomal drugs. Here, we have
      utilized this assay to perform structure-activity investigations of 143 compounds
      containing previously identified alkaloid natural product pharmacophores
      (tryptamines, aporphines and protoberberines) shown to regulate Sm.5HTRL. These
      experiments mapped regions of the tryptamine pharmacophore amenable and
      intolerant to substitution, highlighting differences relative to orthologous
      mammalian 5-HT receptors. Potent Sm.5HTRL antagonists were identified, and the
      efficacy of these compounds were evaluated against live adult parasites cultured
      ex vivo. Such structure-activity profiling, characterizing the effect of various
      modifications to these core ring systems on Sm.5HTRL responses, provides greater
      understanding of pharmacophores selective for this target to aid future drug
      development efforts.

PMID- 30297304
TI  - Reducing repeat imaging in hepato-pancreatico-biliary surgical cancer care
      through shared diagnostic imaging repositories.
AB  - BACKGROUND: With regionalization of care, patients often undergo treatment in
      institutions other than where the initial investigation is conducted. This study
      assessed the impact of a shared diagnostic imaging repository (SDIR) on processes
      of care and outcomes in hepato-pancreatico-biliary (HPB) cancer surgery. METHODS:
      Provincial administrative datasets were linked to study HPB cancer patients
      operated at a regional cancer centre (2003-2014). SDIR and non-SDIR groups were
      based on where initial imaging (CT or MRI) was conducted. Outcomes were repeat
      imaging before surgery and wait times for surgery from initial imaging and
      surgical consultation. RESULTS: Of 839 patients, 474 were from SDIR institutions.
      Fewer SDIR patients underwent any repeat imaging (55.9% vs. 75.3%; p < 0.01) and
      repeat imaging with same modality and protocol (24.7% vs. 43.0%; p < 0.01).
      Median wait time to surgery from initial imaging (64 Vs. 79 days; p < 0.01) and
      surgical consultation (39 Vs. 45 days; p = 0.046) was shorter with SDIR. SDIR
      patients had lower adjusted odds of any repeat imaging (OR 0.20 [0.14-0.30]), and
      repeat imaging with same modality and protocol (OR 0.58 [0.41-0.80]). CONCLUSION:
      Radiology sharing with SDIR reduced repeat imaging for HPB cancer surgery,
      including potentially redundant repeat imaging with same protocol, and shortened
      wait time to surgical care.

PMID- 30297305
TI  - Indocyanine green fluorescence imaging to evaluate graft perfusion during liver
      transplantation.
AB  - BACKGROUND: Primary graft dysfunction (PGD) is a leading cause of graft loss
      after liver transplantation. There is no reliable method to anticipate this
      complication intraoperatively. Indocyanine green (ICG) fluorescence imaging is a
      technique used in hepatobiliary surgery for detection of liver malignancies, but
      has never been reported in the setting of liver transplantation (LT) for function
      assessment. We hypothesized that there could be an association between the type
      of fluorescence and the occurrence of PGD. METHODS: We retrospectively analyzed
      72 patients who underwent LT at our center. An assessment of the liver graft with
      the ICG fluorescence technique was carried out. A classification comprising 3
      types of fluorescence was created after evaluation of the recorded images. We
      assessed the relationship between the type of fluorescence and the occurrence of
      PGD. RESULTS: Crosstabulation analysis of the fluorescent types and occurrence of
      PGD yielded a statistically significant association (p = 0.002). Univariate
      analysis showed that an abnormal ICG fluorescence pattern was a risk factor for
      the occurrence of PGD after LT. CONCLUSIONS: Our findings suggest that there
      could be an association between ICG fluorescence imaging and graft function. This
      intraoperative tool could be useful to detect patients at risk of developing PGD
      after LT.

PMID- 30297306
TI  - The effect of centralization on short term outcomes of pancreatoduodenectomy in a
      universal health care system.
AB  - BACKGROUND: Centralization of pancreatic resections is advocated due to a volume
      outcome association. Pancreatic surgery is in Norway currently performed only in
      five teaching hospitals. The aim was to describe the short-term outcomes after
      pancreatoduodenectomy (PD) within the current organizational model and to assess
      for regional disparities. METHODS: All patients who underwent PD in Norway
      between 2012 and 2016 were identified. Mortality (90 days) and relaparotomy (30
      days) were assessed for predictors including demographic data and multi-visceral
      or vascular resection. Aggregated length-of-stay and national and regional
      incidences of the procedure were also analysed. RESULTS: A total of 930 patients
      underwent PD during the study period. In-hospital mortality occurred in 20
      patients (2%) and 34 patients (4%) died within 90 days. Male gender, age, multi
      visceral resection and relaparotomy were independent predictors of 90-day
      mortality. Some 131 patients (14%) had a relaparotomy, with male gender and multi
      visceral resection as independent predictors. There was no difference between
      regions in procedure incidence or 90-day mortality. There was a disparity within
      the regions in the use of vascular resection (p = 0.021). CONCLUSION: The short
      term outcomes after PD in Norway are acceptable and the 90-day mortality rate is
      low. The outcomes may reflect centralization of pancreatic surgery.

PMID- 30297307
TI  - Mentoring the Next Generation of Authors.
AB  - OBJECTIVES: To discuss the role of mentoring in writing for publication, describe
      the specific needs of millennial learners, and offer tips for both mentor and
      mentee on how to foster and maintain a positive mentorship. DATA SOURCES:
      Published literature, online sources, personal experience. CONCLUSION: Mentorship
      can equip new nurse authors with the confidence, skills, and support needed to
      publish in a variety of forums. While a mentoring relationship primarily benefits
      the mentee, it can be equally rewarding for the mentor. IMPLICATIONS FOR NURSING
      PRACTICE: All oncology nurses have an opportunity to write about some part of
      their role in the care of people with cancer, yet most have not received formal
      training on how best to share their expertise and experience through
      publications. Mentorship can bridge this gap.

PMID- 30297308
TI  - Management of BIRADS 3, 4A, and 4B Lesions Diagnosed as Pure Papilloma by
      Ultrasound-Guided Core Needle Biopsy: Is Surgical Excision Necessary?
AB  - RATIONALE AND OBJECTIVES: There is lack of consensus on managing papillomas due
      to varied upgrade rates in the literature related to variability in the studied
      populations. We specifically studied upgrade rates of pure papilloma diagnosed
      with ultrasound core biopsy (UCB) using spring-loaded (SLB) and vacuum-assisted
      (VAB) biopsy devices in patients with low-to-intermediate pre-test probability
      for malignancy on imaging. MATERIALS & METHODS: From 01/01/2008 to 06/30/2016,
      227 patients with 248 pure papillomas classified as BI-RADS 3, 4a, and 4b were
      diagnosed by UCB and underwent surgical excision or clinical and/or imaging
      follow-up. Imaging features, biopsy device, and final pathology were documented.
      RESULTS: 177 lesions were biopsied with SLB (14-gauge) and 71 lesions with VAB (9
      13 gauges). At surgery, upgrade rates to high-risk lesions and malignancy for SLB
      were 14.3% (22/154) and 1.9% (3/154), and for VAB were 3.5% (2/57) and 0% (0/57),
      respectively (p <0.05). The combined surgical upgrade rate to high-risk lesions
      and malignancy was 11.4% (24/211) and 1.4% (3/211), respectively. The overall
      upgrade rate (including surgical and clinical and/or imaging follow-up) to high
      risk lesions and malignancy was 9.7% (24/248) and 1.2% (3/248), respectively. No
      ultrasound features were predictive of upgrade. Rates of complete excision were
      7.1% (11/154) for SLB and 19.3% (11/57) for VAB (p < 0.05). CONCLUSION: BI-RADS
      3, 4a, or 4b masses biopsied with UCB revealed pure papilloma upgrade to
      malignancy in less than 2% of cases. SLB was associated with greater upgrades
      compared with VAB. Therefore, follow-up imaging is a reasonable alternative to
      excision, particular in those sampled by VAB. Excision could be considered if the
      diagnosis of a high-risk lesion would change clinical management.

PMID- 30297309
TI  - Delivering paediatric critical care in humanitarian settings.

PMID- 30297310
TI  - Dual-Port versus Mono-Port Implantation for Intra-Arterial Chemoinfusion Therapy
      for Treatment of Hepatocellular Carcinoma in Patients with Anatomic Hepatic
      Artery Variation.
AB  - PURPOSE: To compare the feasibility and safety of mono-port catheter system and
      dual-port catheter system for advanced hepatocellular carcinoma (HCC) in patients
      with anatomic hepatic artery variation and portal vein tumor thrombosis.
      MATERIALS AND METHODS: This retrospective study consisted of 22 patients with
      infiltrative or multiple HCC with unilateral or bilateral portal vein thrombosis
      who had hepatic artery variation. A mono-port or dual-port catheter system was
      determined according to the degree of blood supply to the entire tumor through
      the common hepatic and variant hepatic arteries. Intrahepatic perfusion pattern,
      hepatic toxicity, and tumor response were investigated on computed tomography,
      medical records, and follow-up imaging study. RESULTS: The most common hepatic
      arterial variation was replaced right hepatic artery arising from the superior
      mesenteric artery (n = 16), followed by replaced left hepatic artery (n = 5) and
      replaced right posterior segmental artery (n = 1). Twelve patients were treated
      with mono-port catheter system, and 10 patients were treated with dual-port
      catheter system. All 10 patients in the dual-port group showed homogeneous
      distribution of contrast material in the entire liver after port implantation,
      and 6 patients (50%, n = 6/12) in the mono-port group showed heterogeneous
      distribution (P = .018). The objective tumor response rates (P = .361) were 18.2%
      and 40%, and the disease control rates (P = .395) were 36.4% and 60% in the mono
      port and dual-port groups, respectively. CONCLUSIONS: The dual-port ncatheter
      system is a safe and effective technique that allows the even distribution of
      hepatic arterial infusion chemotherapy without hemodynamic modification of
      anatomic variation in the hepatic arteries.

PMID- 30297311
TI  - Risk Assessment of Chronic Kidney Disease following Microwave Ablation for Stage
      T1 Renal Cell Carcinoma.
AB  - PURPOSE: To assess safety and renal-function outcomes after microwave (MW)
      ablation of localized stage T1 renal cell carcinoma (RCC). MATERIALS AND METHODS:
      A retrospective review was conducted of 38 patients (28 men; mean age, 69 y;
      range, 51-88 y) who underwent computed tomography (CT)-guided MW ablation for
      stage T1N0M0 RCC. Baseline and follow-up renal function surrogates including
      creatinine level and estimated glomerular filtration rate (eGFR) were
      statistically compared. Peri- and postoperative complication rates, technical
      success, and treatment response were also assessed. RESULTS: A total of 44 biopsy
      proven stage T1N0M0 RCCs measuring 1.2-6.9 cm (mean, 2.5 cm) were treated, and
      renal function was measured 1 mo after treatment. Mean eGFRs were 60 mL/min/1.73
      m2 at baseline and 59 mL/min/1.73 m2 at 1 month after ablation. At 1-year and
      last follow-ups, the means of difference were 3.3% (95% confidence interval, -4.4
      to 4.3; P = .99) and 3.3% (95% confidence interval, -4.3 to 4.8; P = .91),
      respectively. The 2-years freedom from eGFR decrease to < 60 mL/min/1.73 m2 was
      2% (P = .91). Among the 5 patients (13%) with preexisting stage 4 chronic kidney
      disease (CKD; eGFR < 30 mL/min/1.73 m2) before ablation, there was no significant
      postablative onset of decline or CKD upstaging (P = .001). There were no major
      complications, and 5 patients (13%) had small asymptomatic perinephric hematomas
      (Society of Interventional Radiology minor complication, class A/B) that were
      managed conservatively. CONCLUSIONS: At 2-year follow-up, CT-guided percutaneous
      MW ablation is safe and well-tolerated and achieves nephron preservation similar
      to existing ablative modalities.

PMID- 30297312
TI  - Long-Term Outcomes of Iliofemoral Artery Stents after Transfemoral Aortic Valve
      Replacement.
AB  - PURPOSE: To report long-term results of iliofemoral stent placement after
      transcatheter aortic valve replacement (TAVR). MATERIALS AND METHODS: TAVR access
      related complications treated with iliofemoral stent placement were recorded in
      56 patients (mean age, 81 years; range; 53-93 years; 48% male) of 648 patients
      who underwent TAVR at a single center. Fifty-six patients treated with stent
      placement (40 patients with stent grafts and 16 patients with bare metal stents)
      underwent clinical and ultrasonographic follow-up after a mean of 676 days
      (range, 60-1840 days). RESULTS: During follow-up, none of the 56 patients who had
      stent placement underwent a vascular reintervention of the affected limb, and
      none suffered from limb claudication. No decrease was observed in ankle-brachial
      index (ABI) values to an abnormal value, except in 1 patient (mean preprocedural
      and postprocedural ABI of 1.2 +/- 0.14, range, 0.97-1.4 and 1.19 +/- 0.24, range,
      0.65-1.54, respectively). Arterial duplex assessment showed normal stent flow
      velocity (mean, 168.7 +/- 63.2 cm/sec; range, 80-345 cm/sec) in all but 1
      patient. CONCLUSION: Iliofemoral stent implantation is a safe and efficacious
      treatment for vascular access site and access-related complications during
      transfemoral TAVR.

PMID- 30297313
TI  - Comparison of Clinical Outcomes of Prostatic Artery Embolization with 50-MUm Plus
      100-MUm Polyvinyl Alcohol (PVA) Particles versus 100-MUm PVA Particles Alone: A
      Prospective Randomized Trial.
AB  - PURPOSE: To evaluate the safety and efficacy of prostatic artery embolization
      (PAE) using the combination of 50-MUm and 100-MUm polyvinyl alcohol (PVA)
      particles versus 100-MUm PVA particles alone in the treatment of patients with
      symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Over a 5
      year period, 120 patients treated with PAE for lower urinary tract symptoms
      (LUTS) secondary to BPH were randomized to undergo embolization with 50-MUm plus
      100-MUm PVA particles (group A) or 100-MUm PVA particles alone (group B). Mean
      follow-up time was 34 months (range, 12-57 mo). There were no differences between
      groups regarding baseline data. Primary outcome measurements included change in
      International Prostate Symptom Score (IPSS) and incidence of adverse events.
      Secondary outcome measurements included procedure-associated pain, prostate
      ischemia measured on magnetic resonance (MR) imaging 1 week after PAE, and
      changes over time in quality of life (QOL) questionnaire, peak urinary flow rate
      (Qmax), postvoid residual (PVR) volume, prostate volume (PV), prostate-specific
      antigen (PSA) level, and International Index of Erectile Function (IIEF) were
      evaluated. Recurrence of LUTS following PAE was defined as relief of LUTS
      temporally but increased IPSS >= 8 or QOL score >= 3 or decrease in Qmax to < 7
      mL/s. RESULTS: Mean follow-up periods were 35 months +/- 22 in group A and 33
      months +/- 25 in group B (P = .629). No differences between groups regarding
      procedural details, pain scores, or adverse events were noted (P > .05). At 24
      month of follow-up, patients in group A had a greater decrease in mean IPSS (18.7
      +/- 12.5 vs 14.8 +/- 13.5), QOL score (3.7 +/- 1.5 vs 2.4 +/- 1.8), Qmax (10.5 mL
      +/- 9.5 vs 6.8 mL +/- 5.0), PVR (92.0 mL +/- 75.0 vs 60.0 mL +/- 55.0), and PV
      (37.0 mL +/- 19.5 vs 25.5 mL +/- 15.0) compared with patients in group B (P < .05
      for all). Mean ratios of prostate ischemic volume at 1 week after PAE were 70% +/
      20 in group A and 41% +/- 25 in group B (P = .021); mean PSA levels at 24 hour
      after PAE were 92.5 ng/mL +/- 55.0 in group A and 77.5 ng/mL +/- 45.0 in group B
      (P = .031); LUTS recurrence rates were 3.6% in group A and 14.6% in group B (P =
      .024). The mean IIEF-5 was not significantly different from baseline in either
      group. CONCLUSIONS: PAE with 50-MUm plus 100-MUm PVA particles resulted in
      greater improvement in clinical and imaging outcomes and no significant
      differences in adverse events compared with 100-MUm PVA particles alone.

PMID- 30297314
TI  - Does intra-uterine insemination have a place in modern ART practice?
AB  - Intra-uterine insemination (IUI) is a cheaper, less intensive treatment modality
      for achieving a pregnancy in couples with specific indications. The use of IUI
      seems to have declined after NICE guideline 2013 (CG 156) recommended IVF over
      IUI in couples with unexplained and mild male factor infertility. This review
      examines the current evidence and the applicability of IUI as a first-line option
      of treatment in couples with unexplained and mild male factor subfertility. The
      outcome of the review supports this argument. It is likely that IUI will re
      emerge as an effective treatment option and thereby increase the choice to
      patients. However, there is a need for ongoing research and investment into
      funding of good quality trials to improve and strengthen the evidence base.

PMID- 30297315
TI  - Implementation of an Automated Pediatric Malnutrition Screen Using Anthropometric
      Measurements in the Electronic Health Record.

PMID- 30297316
TI  - Delusional misidentification of inanimate objects, persons, and places after a
      left orbitofrontal cortex injury.

PMID- 30297317
TI  - Corrigendum to "Antidepressant activity of vorinostat is associated with
      amelioration of oxidative stress and inflammation in a corticosterone-induced
      chronic stress model in mice." [Behav. Brain Res. 344 (2018) 73-84].

PMID- 30297319
TI  - Gestational Diabetes Mellitus: Mechanisms, Treatment, and Complications.
AB  - Gestational diabetes mellitus (GDM) is the most common metabolic disturbance
      during pregnancy. The prevalence is rising and correlates with the increase in
      maternal obesity over recent decades. The etiology of GDM is complex, with
      genetic and environmental factors implicated in mechanistic and epidemiological
      studies. GDM begets important short- and long-term health risks for the mother,
      developing fetus, and offspring. This includes the high likelihood of subsequent
      maternal type 2 diabetes (T2DM), and possible adverse cardiometabolic phenotypes
      in the offspring. The most clinically and cost-effective methods of screening for
      GDM remain uncertain. Whilst treatments with lifestyle and pharmacological
      interventions have demonstrated short-term benefits, the long-term impact for the
      offspring of intrauterine exposure to antidiabetic medication remains unclear.

PMID- 30297318
TI  - Hypertensive ED patients: Missed opportunities for addressing hypertension and
      facilitating outpatient follow-up.
AB  - OBJECTIVES: Hypertension is a leading cause of morbidity and mortality. The
      emergency department (ED) frequently serves populations with unmet health needs
      and could have a greater and more systematic role in secondary prevention for
      hypertension. This study sought to determine, among hypertensive patients
      discharged from the ED, the frequency that patients 1) received hypertension
      specific education, and 2) followed-up with a primary care provider. We
      secondarily assessed participant beliefs about hypertension. METHODS: This non
      experimental, observational study enrolled a convenience sample of consenting
      patients with asymptomatic, markedly elevated blood pressure (systolic >=160 mmHg
      or diastolic >=100 mmHg) with medium to low triage acuity discharged from an
      urban, academic ED. Discharge instructions were assessed through chart review.
      Patients followed up per their normal routine without intervention. Participants
      were interviewed by phone two to four weeks after ED discharge to ascertain
      outpatient follow-up and describe beliefs about hypertension. RESULTS: From April
      through June 2014, 200 patients were approached, of whom 90 were enrolled. Of
      these, 77% of patients reported a previous diagnosis of hypertension, and 60%
      reported current treatment with antihypertensive medications. Five patients
      (5.5%) received written instructions at discharge addressing hypertension,
      although 59 (65.6%) reported that they were informed about their elevated blood
      pressure during the ED visit. Follow-up with a primary care provider within 2-4
      weeks of discharge was completed in 57% of cases. None of the patients who
      received hypertension-specific discharge instructions completed follow-up.
      CONCLUSIONS: Over half of markedly hypertensive patients discharged from the ED
      followed up with primary care within four weeks. Nonetheless, missed
      opportunities for improved secondary prevention among ED patients with
      hypertension are common. There is an urgent need for evidence-based interventions
      to assist emergency departments in addressing this health threat.

PMID- 30297320
TI  - Central Obesity, Faster Maturation, and 'PCOS' in Girls.
AB  - Polycystic ovary syndrome (PCOS) development commonly starts with a mismatch
      between pre- and postnatal weight gain, leading to hepatovisceral fat excess. To
      escape from such central obesity, girls may accelerate their growth and/or
      maturation. This homeostatic mechanism is lost upon reaching adult height, and
      PCOS may ensue. Prevention and/or treatment of PCOS should aim at reducing
      central fat excess.

PMID- 30297321
TI  - The need for new treatment recommendations for trichomoniasis among women.

PMID- 30297323
TI  - Can transcranial electric stimulation with multiple electrodes reach deep
      targets?
AB  - To reach a deep target in the brain with transcranial electric stimulation (TES),
      currents have to pass also through the cortical surface. Thus, it is generally
      thought that TES cannot achieve focal deep brain stimulation. Recent efforts with
      interfering waveforms and pulsed stimulation have argued that one can achieve
      deeper or more intense stimulation in the brain. Here we argue that conventional
      transcranial stimulation with multiple current sources is just as effective as
      these new approaches. The conventional multi-electrode approach can be
      numerically optimized to maximize intensity or focality at a desired target
      location. Using such optimal electrode configurations we find in a detailed and
      realistic head model that deep targets may in fact be strongly stimulated, with
      cerebro-spinal fluid guiding currents deep into the brain.

PMID- 30297324
TI  - The physiological role of the free 20S proteasome in protein degradation: A
      critical review.
AB  - BACKGROUND: It has been almost three decades since the removal of oxidized
      proteins by the free 20S catalytic unit of the proteasome (20SPT) was proposed.
      Since then, experimental evidence suggesting a physiological role of proteolysis
      mediated by the free 20SPT has being gathered. SCOPE OF REVIEW: Experimental data
      that favors the hypothesis of free 20SPT as playing a role in proteolysis are
      critically reviewed. MAJOR CONCLUSIONS: Protein degradation by the proteasome may
      proceed through multiple proteasome complexes with different requirements though
      the unequivocal role of the free 20SPT in cellular proteolysis towards native or
      oxidized proteins remains to be demonstrated. GENERAL SIGNIFICANCE: The
      biological significance of proteolysis mediated by the free 20SPT has been
      elusive since its discovery. The present review critically analyzes the available
      experimental data supporting the proteolytic role of the free or single capped
      20SPT.

PMID- 30297322
TI  - Single-dose versus 7-day-dose metronidazole for the treatment of trichomoniasis
      in women: an open-label, randomised controlled trial.
AB  - BACKGROUND: Among women, trichomoniasis is the most common non-viral sexually
      transmitted infection worldwide, and is associated with serious reproductive
      morbidity, poor birth outcomes, and amplified HIV transmission. Single-dose
      metronidazole is the first-line treatment for trichomoniasis. However, bacterial
      vaginosis can alter treatment efficacy in HIV-infected women, and single-dose
      metronidazole treatment might not always clear infection. We compared single-dose
      metronidazole with a 7-day dose for the treatment of trichomoniasis among HIV
      uninfected, non-pregnant women and tested whether efficacy was modified by
      bacterial vaginosis. METHODS: In this multicentre, open-label, randomised
      controlled trial, participants were recruited at three sexual health clinics in
      the USA. We included women positive for Trichomonas vaginalis infection according
      to clinical screening. Participants were randomly assigned (1:1) to receive
      either a single dose of 2 g of metronidazole (single-dose group) or 500 mg of
      metronidazole twice daily for 7 days (7-day-dose group). The randomisation was
      done by blocks of four or six for each site. Patients and investigators were
      aware of treatment assignment. The primary outcome was T vaginalis infection by
      intention to treat, at test-of-cure 4 weeks after completion of treatment. The
      analysis of the primary outcome per nucleic acid amplification test or culture
      was also stratified by bacterial vaginosis status. This trial is registered with
      ClinicalTrials.gov, number NCT01018095, and with the US Food and Drug
      Administration, number IND118276, and is closed to accrual. FINDINGS:
      Participants were recruited from Oct 6, 2014, to April 26, 2017. Of the 1028
      patients assessed for eligibility, 623 women were randomly assigned to treatment
      groups (311 women in the single-dose group and 312 women in the 7-day-dose group;
      intention-to-treat population). Although planned enrolment had been 1664 women,
      the study was stopped early because of funding limitations. Patients in the 7-day
      dose group were less likely to be T vaginalis positive at test-of-cure than those
      in the single-dose group (34 [11%] of 312 vs 58 [19%] of 311, relative risk 0.55,
      95% CI 0.34-0.70; p<0.0001). Bacterial vaginosis status had no significant effect
      on relative risk (p=0.17). Self-reported adherence was 96% in the 7-day-dose
      group and 99% in the single-dose group. Side-effects were similar by group; the
      most common side-effect was nausea (124 [23%]), followed by headache (38 [7%])
      and vomiting (19 [4%]). INTERPRETATION: The 7-day-dose metronidazole should be
      the preferred treatment for trichomoniasis among women. FUNDING: National
      Institutes of Health.

PMID- 30297325
TI  - Antibodies targeting protein-arginine deiminase 4 (PAD4) demonstrate diagnostic
      value in rheumatoid arthritis.

PMID- 30297326
TI  - Interaction between B-cell activation factor and methotrexate impacts
      immunogenicity of seasonal influenza vaccination in patients with rheumatoid
      arthritis.

PMID- 30297327
TI  - Wrist ultrasound - the model method for grey-scale and power Doppler scoring.

PMID- 30297328
TI  - Extraintestinal translocation of microbes and tissue specificity in rheumatic
      musculoskeletal disease (RMD): its more than a gut feeling.

PMID- 30297329
TI  - Effect of in utero hydroxychloroquine exposure on the development of cutaneous
      neonatal lupus erythematosus.
AB  - OBJECTIVE: Cutaneous neonatal lupus (cNL) occurs in possibly 5%-16% of anti-Ro+/
      anti-La antibody-exposed infants. Data suggest in utero exposure to
      hydroxychloroquine (HCQ) may prevent cardiac NL. The aim was to assess whether in
      utero exposure to HCQ decreases the risk of cNL and/or delays onset. METHODS: A
      multicentre case-control study was performed with 122 cNL cases and 434 controls
      born to women with a rheumatological disease who had documentation of maternal
      anti-Ro+/-anti-La antibodies at pregnancy and confirmation of medication use and
      the child's outcome. A secondary analysis was performed on 262 cNL cases,
      irrespective of maternal diagnosis, to determine if HCQ delayed time to cNL
      onset. RESULTS: Twenty (16%) cNL cases were exposed to HCQ compared with 146
      (34%) controls (OR 0.4 (95% CI 0.2 to 0.6); p<0.01). Exposure to HCQ was
      associated with a reduced risk of cNL; exposure to anti-La antibody and female
      gender were associated with an increased risk of cNL. Exposure to HCQ remained
      significantly associated with a reduced cNL risk in the analyses limited to
      mothers with systemic lupus erythematosus and those who developed rash <=1 month.
      When analysing all 262 cNL cases, HCQ-exposed infants were older (6.0 (95% CI 5.7
      to 6.3) weeks) at cNL onset versus HCQ-non-exposed infants (4.4 (95% CI 3.9 to
      5.0) weeks), but the difference was not statistically significant (p=0.21).
      CONCLUSION: Exposure to HCQ was associated with a reduced risk of cNL. Among cNL
      cases, those exposed to HCQ tend to have later onset of rash. Both findings
      suggest a protective effect of HCQ on cNL.

PMID- 30297330
TI  - Why did IL-23p19 inhibition fail in AS: a tale of tissues, trials or translation?

PMID- 30297332
TI  - Incidence, prevalence and treatment burden of polymyalgia rheumatica in the UK
      over two decades: a population-based study.
AB  - OBJECTIVE: Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic
      disease in older people. Contemporary estimates of the incidence and prevalence
      are lacking, and no previous study has assessed treatment patterns at a
      population level. This study aims to address this. METHODS: We extracted
      anonymised electronic medical records of patients over the age of 40 years from
      the Clinical Practice Research Datalink in the period 1990-2016. The absolute
      rate of PMR per 100 000 person-years was calculated and stratified by age, gender
      and calendar year. Incidence rate ratios were calculated using a Poisson
      regression model. Among persons with PMR, continuous and total duration of
      treatment with glucocorticoids (GC) were assessed. RESULTS: 5 364 005 patients
      were included who contributed 44 million person-years of follow-up. 42 125 people
      had an incident diagnosis of PMR during the period. The overall incidence rate of
      PMR was 95.9 per 100 000 (95% CI 94.9 to 96.8). The incidence of PMR was highest
      in women, older age groups and those living in the South of England. Incidence
      appears stable over time. The prevalence of PMR in 2015 was 0.85 %. The median
      (IQR) continuous GC treatment duration was 15.8 (7.9-31.2) months. However,
      around 25% of patients received more than 4 years in total of GC therapy.
      CONCLUSIONS: The incidence rates of PMR have stabilised. This is the first
      population-based study to confirm that a significant number of patients with PMR
      receive prolonged treatment with GC, which can carry significant risks. The early
      identification of these patients should be a priority in future research.

PMID- 30297331
TI  - Identification of a distinct imaging phenotype may improve the management of
      palindromic rheumatism.
AB  - OBJECTIVES: To use high-resolution imaging to characterise palindromic rheumatism
      (PR) and to compare the imaging pattern observed to that seen in new-onset
      rheumatoid arthritis (NORA). METHODS: Ultrasound (US) assessment of synovitis,
      tenosynovitis and non-synovial extracapsular inflammation (ECI) was performed
      during and between flares in a prospective treatment-naive PR cohort. MRI of the
      flaring region was performed where possible. For comparison, the same US
      assessment was also performed in anticyclic citrullinated peptide (CCP) positive
      individuals with musculoskeletal symptoms (CCP+ at risk) and patients with NORA.
      RESULTS: Thirty-one of 79 patients with PR recruited were assessed during a
      flare. A high frequency of ECI was identified on US; 19/31 (61%) of patients had
      ECI including 12/19 (63%) in whom ECI was identified in the absence of synovitis.
      Only 7/31 (23%) patients with PR had synovitis (greyscale >=1 and power Doppler
      >=1) during flare. In the hands/wrists, ECI was more prevalent in PR compared
      with NORA and CCP+ at risk (65% vs 29 % vs 6%, p<0.05). Furthermore, ECI without
      synovitis was specific for PR (42% PR vs 4% NORA (p=0.003) and 6% CCP+ at risk
      (p=0.0012)). Eleven PR flares were captured by MRI, which was more sensitive than
      US for synovitis and ECI. 8/31 (26%) patients with PR developed RA and had a
      similar US phenotype to NORA at progression. CONCLUSION: PR has a distinct US
      pattern characterised by reversible ECI, often without synovitis. In patients
      presenting with new joint swelling, US may refine management by distinguishing
      relapsing from persistent arthritis.

PMID- 30297333
TI  - Rheumatoid arthritis-associated DNA methylation sites in peripheral blood
      mononuclear cells.
AB  - OBJECTIVES: To identify novel DNA methylation sites significant for rheumatoid
      arthritis (RA) and comprehensively understand their underlying pathological
      mechanism. METHODS: We performed (1) genome-wide DNA methylation and mRNA
      expression profiling in peripheral blood mononuclear cells from RA patients and
      health controls; (2) correlation analysis and causal inference tests for DNA
      methylation and mRNA expression data; (3) differential methylation genes
      regulatory network construction; (4) validation tests of 10 differential
      methylation positions (DMPs) of interest and corresponding gene expressions; (5)
      correlation between PARP9 methylation and its mRNA expression level in Jurkat
      cells and T cells from patients with RA; (6) testing the pathological functions
      of PARP9 in Jurkat cells. RESULTS: A total of 1046 DNA methylation positions were
      associated with RA. The identified DMPs have regulatory effects on mRNA
      expressions. Causal inference tests identified six DNA methylation-mRNA-RA
      regulatory chains (eg, cg00959259-PARP9-RA). The identified DMPs and genes formed
      an interferon-inducible gene interaction network (eg, MX1, IFI44L, DTX3L and
      PARP9). Key DMPs and corresponding genes were validated their differences in
      additional samples. Methylation of PARP9 was correlated with mRNA level in Jurkat
      cells and T lymphocytes isolated from patients with RA. The PARP9 gene exerted
      significant effects on Jurkat cells (eg, cell cycle, cell proliferation, cell
      activation and expression of inflammatory factor IL-2). CONCLUSIONS: This
      multistage study identified an interferon-inducible gene interaction network
      associated with RA and highlighted the importance of PARP9 gene in RA
      pathogenesis. The results enhanced our understanding of the important role of DNA
      methylation in pathology of RA.

PMID- 30297335
TI  - Vitamin D supplements do not protect bone health, analysis finds.

PMID- 30297334
TI  - Risk-adjusted mortality of VLBW infants in high-volume versus low-volume NICUs.
AB  - OBJECTIVE: To examine whether the number of very low birthweight (VLBW) infants
      treated annually in neonatal intensive care units (NICUs) (hospital volume) has
      an effect on their in-hospital mortality under the regulatory conditions in
      Germany. SETTING: The study included VLBW infants with <33 weeks of gestational
      age and birth weight below 1500 g admitted to NICUs in the state of Baden
      Wuerttemberg, Germany, from 2003 to 2008. Cases were extracted from the
      compulsory German neonatal quality assurance programme with variables essential
      for calculation of the Clinical Risk Index for Babies (CRIB) and PREM birth model
      (PREM(bm)) scores. The cohort was divided into four subgroups corresponding to
      their disease severity (low, intermediate, high and very high) according to each
      score. Low-volume NICUs (LV-NICUs) were defined as treating up to 50 cases per
      year, while high-volume NICUs >50 cases. RESULTS: After exclusion of infants with
      lethal malformations, 5340 cases from 32 units were analysed. While raw mortality
      was comparable, infants in LV-NICUs had an increased mortality after risk
      adjustment with the CRIB and PREM(bm) scores (OR 1.48 (95% CI 1.16 to 1.90),
      p=0.002 with CRIB; and OR 1.39 (95% CI 1.11 to 1.76), p=0.005 with PREM(bm)). In
      a subgroup analysis mortality was significantly higher for LV-NICUs in the
      intermediate disease severity group (OR 1.49 (95% CI 1.02 to 2.17), p=0.037 with
      CRIB) and in the high-risk group (OR 1.70 (95% CI 1.16 to 1.90), p=0.002 with
      CRIB; and OR 1.39 (95% CI 1.11 to 1.76), p=0.005 with PREM(bm)), but not in the
      low-risk and very high-risk subgroups. CONCLUSION: Depending on the severity of
      the disease, the risk-adjusted mortality in German NICUs with 50 or less annual
      cases of VLBW infants may be significantly increased.

PMID- 30297336
TI  - Novel gene targets for miRNA146a and miRNA155 in anterior uveitis.
AB  - BACKGROUND/AIMS: Anterior uveitis (AU) is the most common form of intraocular
      inflammation. MicroRNAs (miRNA) are small, non-coding RNAs functioning as post
      transcriptional repressors of gene expression. Knowledge of miRNAs can implicate
      specific genes and pathogenic signalling pathways in disease. This study examines
      miRNA expression, function and target genes in AU pathogenesis. METHODS: AU and
      healthy control (HC) peripheral blood mononuclear cells (PBMC) were initially
      screened for expression of five miRNAs by real-time PCR. Regulation of the
      aberrantly expressed miRNAs by TLR1/2, TLR3, TLR4, IL1beta and TNFalpha was
      quantified by real-time PCR and paired cytokine outputs measured by ELISA.
      Functional effects of miRNA overexpression using transfected THP1 cells examined
      IL6, IL8, IL10 and IL1beta cytokine outputs by ELISA. Target genes were
      identified using TargetScan online computational algorithm and relevant targets
      verified by cloning of the 3'UTR and luciferase reporter gene assays. RESULTS:
      Increased expression of miRNA146a (p<0.01), miRNA155 (p<0.05) and miRNA125a5p
      (p<0.01) was demonstrated in AU PBMC compared with HC. miRNA155 was increased
      following TLR1/2 (p<0.05) and TLR4 (p<0.05) stimulation and miRNA146a increased
      in response to IL1beta (p<0.05). In a proinflammatory environment, miRNA155
      overexpression in THP1 cells yielded increased cytokine output whereas miRNA146a
      overexpression showed decreased cytokine output. CD80, PRKCE and VASN were
      confirmed as novel targets for miRNA146a and SMAD2, TYRP1 and FBXO22 for
      miRNA155. CONCLUSION: This study identifies overexpression of proinflammatory
      miRNA155, regulatory miRNA146a and miRNA125a-5p in AU. CD80, PRKCE and VASN are
      novel miRNA146a targets and SMAD2, TYRP1 and FBXO22 are novel targets for
      miRNA155.

PMID- 30297338
TI  - Who are Sierra Leone's health security efforts for?

PMID- 30297337
TI  - Macular spatial distribution of preserved autofluorescence in patients with
      choroideremia.
AB  - BACKGROUND/AIMS: To better understand the pattern of degeneration progression in
      cases with choroideremia. METHODS: A cohort of genotypically confirmed
      choroideremia cases who underwent optical coherence tomography (OCT) and fundus
      autofluorescence (FAF) imaging was studied. Using HEYEX review software, the
      foveal centre was marked on FAF images under guidance of corresponding OCT
      images, followed by application of an ETDRS grid. The boundaries of preserved
      autofluorescence (AF) were manually segmented in each individual ETDRS subfield.
      The regional distribution of preserved AF was assessed by comparing its area
      among the various subfields. RESULTS: A total of 168 eyes from 84 choroideremia
      cases were enrolled. There was a statistically significant difference in the
      amount of preserved AF area between inner subfields as determined by one-way
      analysis of variance (F (3,668)=9.997, p<0.001) and also between outer subfields
      (F (3,668)=8.348, p<0.001). A Tukey posthoc test revealed that the preserved AF
      area in the nasal subfields in both the inner and outer subfields was
      significantly smaller compared with analogue subfields. CONCLUSION: The
      asymmetric spatial distribution of preserved AF in choroideremia (corresponding
      to the stellate shaped nature of these regions) suggests that the progression of
      degeneration has directional preference.

PMID- 30297340
TI  - RNA Splicing in the Transition from B Cells to Antibody-Secreting Cells: The
      Influences of ELL2, Small Nuclear RNA, and Endoplasmic Reticulum Stress.
AB  - In the transition from B cells to Ab-secreting cells (ASCs) many genes are
      induced, such as ELL2, Irf4, Prdm1, Xbp1, whereas other mRNAs do not change in
      abundance. Nonetheless, using splicing array technology and mouse splenic B cells
      plus or minus LPS, we found that induced and "uninduced" genes can show large
      differences in splicing patterns between the cell stages, which could influence
      ASC development. We found that ~55% of these splicing changes depend on ELL2, a
      transcription elongation factor that influences expression levels and splicing
      patterns of ASC signature genes, genes in the cell-cycle and N-glycan
      biosynthesis and processing pathways, and the secretory versus membrane forms of
      the IgH mRNA. Some of these changes occur when ELL2 binds directly to the genes
      encoding those mRNAs, whereas some of the changes are indirect. To attempt to
      account for the changes that occur in RNA splicing before or without ELL2
      induction, we examined the amount of the small nuclear RNA molecules and found
      that they were significantly decreased within 18 h of LPS stimulation and stayed
      low until 72 h. Correlating with this, at 18 h after LPS, endoplasmic reticulum
      stress and Ire1 phosphorylation are induced. Inhibiting the regulated Ire1
      dependent mRNA decay with 4u8C correlates with the reduction in small nuclear RNA
      and changes in the normal splicing patterns at 18 h. Thus, we conclude that the
      RNA splicing patterns in ASCs are shaped early by endoplasmic reticulum stress
      and Ire1 phosphorylation and later by ELL2 induction.

PMID- 30297339
TI  - Differential and Overlapping Immune Programs Regulated by IRF3 and IRF5 in
      Plasmacytoid Dendritic Cells.
AB  - We examined the signaling pathways and cell type-specific responses of IFN
      regulatory factor (IRF) 5, an immune-regulatory transcription factor. We show
      that the protein kinases IKKalpha, IKKbeta, IKKepsilon, and TANK-binding kinase 1
      each confer IRF5 phosphorylation/dimerization, thus extending the family of IRF5
      activator kinases. Among primary human immune cell subsets, we found that IRF5 is
      most abundant in plasmacytoid dendritic cells (pDCs). Flow cytometric cell
      imaging revealed that IRF5 is specifically activated by endosomal TLR signaling.
      Comparative analyses revealed that IRF3 is activated in pDCs uniquely through RIG
      I-like receptor (RLR) signaling. Transcriptomic analyses of pDCs show that the
      partitioning of TLR7/IRF5 and RLR/IRF3 pathways confers differential gene
      expression and immune cytokine production in pDCs, linking IRF5 with immune
      regulatory and proinflammatory gene expression. Thus, TLR7/IRF5 and RLR-IRF3
      partitioning serves to polarize pDC response outcome. Strategies to
      differentially engage IRF signaling pathways should be considered in the design
      of immunotherapeutic approaches to modulate or polarize the immune response for
      specific outcome.

PMID- 30297341
TI  - Can rapid approaches to qualitative analysis deliver timely, valid findings to
      clinical leaders? A mixed methods study comparing rapid and thematic analysis.
AB  - OBJECTIVES: This study compares rapid and traditional analyses of a UK health
      service evaluation dataset to explore differences in researcher time and
      consistency of outputs. DESIGN: Mixed methods study, quantitatively and
      qualitatively comparing qualitative methods. SETTING: Data from a home birth
      service evaluation study in a hospital in the English National Health Service,
      which took place between October and December 2014. Two research teams
      independently analysed focus group and interview transcript data: one team used a
      thematic analysis approach using the framework method, and the second used rapid
      analysis. PARTICIPANTS: Home birth midwives (6), midwifery support workers (4),
      commissioners (4), managers (6), and community midwives (12) and a patient
      representative (1) participated in the original study. PRIMARY OUTCOME MEASURES:
      Time taken to complete analysis in person hours; analysis findings and
      recommendations matched, partially matched or not matched across the two teams.
      RESULTS: Rapid analysis data management took less time than thematic analysis (43
      hours vs 116.5 hours). Rapid analysis took 100 hours, and thematic analysis took
      126.5 hours in total, with interpretation and write up taking much longer in the
      rapid analysis (52 hours vs 8 hours). Rapid analysis findings overlapped with 79%
      of thematic analysis findings, and thematic analysis overlapped with 63% of the
      rapid analysis findings. Rapid analysis recommendations overlapped with 55% of
      those from the thematic analysis, and thematic analysis overlapped with 59% of
      the rapid analysis recommendations. CONCLUSIONS: Rapid analysis delivered a
      modest time saving. Excessive time to interpret data in rapid analysis in this
      study may be due to differences between research teams. There was overlap in
      outputs between approaches, more in findings than recommendations. Rapid analysis
      may have the potential to deliver valid, timely findings while taking less time.
      We recommend further comparisons using additional data sets with more similar
      research teams.

PMID- 30297342
TI  - Comparative, cross-sectional study of the format, content and timing of
      medication safety letters issued in Canada, the USA and the UK.
AB  - OBJECTIVES: To assess consistency in the format and content, and overlap of
      subject and timing, of medication safety letters issued by regulatory health
      authorities to healthcare providers in Canada, the USA and the UK. DESIGN: A
      cross-sectional study comparing medication safety letters issued for the purpose
      of alerting healthcare providers to newly identified medication problems
      associated with medications already on the market. SETTING: Online databases
      operated by Health Canada, the US Food and Drug Administration and the UK
      Medicines and Healthcare products Regulatory Agency were searched to select
      medication safety letters issued between 1 January 2010 and 31 December 2014.
      Format, content and timing of each medication safety letter were assessed using
      an abstraction tool comprising 21 characteristics deemed relevant by consensus of
      the research team. MAIN OUTCOME MEASURES: Main outcome measures included, first,
      characteristics (format and content) of medication safety letters and second,
      overlap of subject and release date across countries. RESULTS: Of 330 medication
      safety letters identified, 227 dealt with unique issues relating to medications
      available in all three countries. Of these 227 letters, 21 (9%) medication
      problems were the subject of letters released in all three countries; 40 (18%) in
      two countries and 166 (73%) in only one country. Only 13 (62%) of the 21 letters
      issued in all three countries were released within 6 months of each other.
      CONCLUSIONS: Significant discrepancies in both the subject and timing of
      medication safety letters issued by health authorities in three countries
      (Canada, the USA and the UK) where medical practice is otherwise comparable,
      raising questions about why, how and when medication problems are identified and
      communicated to healthcare providers by the authorities. More rapid communication
      of medication problems and better alignment between authorities could enhance
      patient safety.

PMID- 30297343
TI  - Comparison of simulation debriefs with traditional needs assessment methods: a
      qualitative exploratory study in a critical care community setting.
AB  - OBJECTIVE: To better understand the potential of a needs assessment approach
      using qualitative data from manikin-based and virtual patient simulation
      debriefing sessions compared with traditional data collection methods (ie, focus
      groups and interviews). DESIGN: Original data from simulation debrief sessions
      was compared and contrasted with data from an earlier assessment of critical care
      needs in a community setting (using focus groups and interviews), thus
      undertaking secondary analysis of data. Time and cost data were also examined.
      Debrief sessions were coded using deductive and inductive techniques. Matrices
      were used to explore the commonalities, differences and emergent findings across
      the methods. SETTING: Critical care unit in a community hospital setting.
      RESULTS: Interviews and focus groups yielded 684 and 647 min of audio-recordings,
      respectively. The manikin-based debrief recordings averaged 22 min (total=130
      min) and virtual patient debrief recordings averaged 31 min (total=186 min). The
      approximate cost for the interviews and focus groups was $13 560, for manikin
      based simulation debriefs was $4030 and for the virtual patient debriefs was
      $3475. Fifteen of 20 total themes were common across the simulation debriefs and
      interview/focus group data. Simulation-specific themes were identified, including
      fidelity (environment, equipment and psychological) and the multiple roles of the
      simulation instructor (educative, promoting reflection and assessing needs).
      CONCLUSIONS: Given current fiscal realities, the dual benefit of being educative
      and identifying needs is appealing. While simulation is an innovative method to
      conduct needs assessments, it is important to recognise that there are trade-offs
      with the selection of methods.

PMID- 30297345
TI  - Validation of billing code combinations to identify cardiovascular magnetic
      resonance imaging scans in Ontario, Canada: a retrospective cohort study.
AB  - OBJECTIVES: Cardiovascular magnetic resonance (CMR) imaging is the gold-standard
      test for the assessment of heart function. Despite its importance, many
      jurisdictions lack specific billing codes that can be used to identify patient
      receipt of CMR in administrative databases, limiting the ability to perform 'big
      data' CMR studies. Our objective was to identify the optimal billing code
      combination to identify patients who underwent CMR using administrative data in
      Ontario. DESIGN: Retrospective cohort study. SETTING: Quaternary care academic
      referral centre in Ontario, Canada. PARTICIPANTS: We tested all billing code
      combinations in order to identify the optimal one to determine receipt of CMR.
      The reference gold standard was a list of all cardiothoracic magnetic resonance
      scans performed at Sunnybrook Health Sciences Centre between 1 January 2014 and
      31 December 2016, verified by chart audit. We assessed the diagnostic performance
      (accuracy, sensitivity, specificity, positive predictive value and negative
      predictive value) for all code combinations. RESULTS: Our gold-standard cohort
      consisted of 2339 thoracic MRIs that were performed at Sunnybrook Health Sciences
      Centre from 1 January 2014 to 31 December 2016. Of these, 2139 (91.5%) were CMRs
      and 200 (8.5%) were chest MRIs. We identified the most accurate billing
      combination for the determination of patient receipt of CMR. This combination
      resulted in an accuracy of 95.3% (95% CI 94.4% to 96.2%), sensitivity of 97.4%
      (95% CI 96.6% to 98.1%), specificity of 86.4% (95% CI 83.1% to 89.6%), positive
      predictive value of 96.9% (95% CI 96.1% to 97.6%) and negative predictive value
      of 88.4% (95% CI 85.4% to 91.5%). CONCLUSIONS: Our study is the first to verify
      the ability to accurately identify patient receipt of CMR using administrative
      data, facilitating more robust population-based CMR studies in the future.

PMID- 30297344
TI  - Testing the information-motivation-behavioural skills model of diabetes self
      management among Chinese adults with type 2 diabetes: a protocol of a 3-month
      follow-up study.
AB  - INTRODUCTION: Currently, China leads the world in the number of people with
      diabetes, making it home to a third of the global diabetic population. Persons
      with diabetes have to carry out 95% of their self-care. As an important component
      of diabetes care, diabetes self-management (DSM) is defined as everyday
      behaviours that persons carry out to control diabetes. Consistent findings have
      been reported that level of compliance to suggested DSM behaviours is not
      considered optimal among Chinese adults with type 2 diabetes (T2D). The
      underlying reasons for suboptimal DSM behaviours among Chinese adults are not
      well known and no conceptual model has been developed to guide DSM interventions
      in this population. Although the information-motivation-behavioural skills model
      has been tested among Chinese adults with T2D, some key components of the
      original model were not tested. In this proposed study protocol, we will refine
      and test a culturally tailored model of DSM longitudinally among 250 Chinese
      adults residing in China. METHODS AND ANALYSIS: This is a descriptive, repeated
      measure study to be conducted at a tertiary hospital in Chengdu, China. A total
      of 250 adults with T2D will be enrolled and followed for 3 months in this study.
      Information of multiple domains will be collected, including demographics,
      diabetes knowledge, health education form, provider-patient communication, health
      beliefs, social support, diabetes self-efficacy, the medical coping modes, the
      diabetes self-care, depression, diabetes-dependent quality of life, haemoglobin
      A1c, blood pressure and blood lipids at baseline and 3-month follow-up. Main
      analyses comprise linear regression modelling controlling for covariates and
      structural equation modelling. ETHICS AND DISSEMINATION: Ethical approval has
      been obtained through the Fourth People's Hospital of Chengdu Research Ethics
      Committee (study approval number 2017017). We aim to disseminate the findings
      through international conferences, international peer-reviewed journals and
      social media. TRIAL REGISTRATION NUMBER: ChiCTR-ROC-17013592.

PMID- 30297346
TI  - Visibility of tobacco products and advertisement at the point of sale: a
      systematic audit of retailers in Amsterdam.
AB  - OBJECTIVES: Visibility of tobacco products at the point of sale (PoS), in
      settings where open display of tobacco is allowed, is one of the last remaining
      ways in which the tobacco industry can legally promote their products. The aim of
      this study was to map the visibility of tobacco products and advertisement both
      inside and outside retailers, among different types of retailers. SETTING: The
      study was conducted in two districts in Amsterdam, the Netherlands. PARTICIPANTS:
      All potential tobacco retailers were visited within the districts, and were
      mapped using Global Positioning System (GPS) coordinates. INTERVENTION:
      Observational data was collected for each tobacco retailer using a checklist with
      characteristics of the internal and external visibility of tobacco products and
      advertisement. Retailers were categorised into supermarkets, hospitality
      industry, tobacconists and 'other retailers' (convenience stores, office supply
      stores, gas stations, drug stores and telephone communication stores). Data were
      collected in April-May 2017. RESULTS: Eighty-two tobacco retailers were
      identified. Among all retailers, 52.4% had external and 91.5% internal visibility
      of tobacco products. Tobacconists had the highest level of internal and external
      visibility of tobacco products (both 100%), followed by 'other retailers' (100%
      and 56% respectively) and supermarkets (79% and 47%, respectively). Retailers in
      the hospitality industry had low external visibility (28%), but high internal
      visibility (90%), as 83% sold tobacco through vending machines. CONCLUSION:
      Visibility of tobacco products was high among all types of retailers, including
      those previous studies show are commonly visited by youth.

PMID- 30297347
TI  - Protocol for a scoping review on nursing care and the autonomy of disabled
      persons.
AB  - INTRODUCTION: Considering the limitations that disabled persons experience, our
      understanding of caring for these people has evolved over time worldwide. Because
      nursing care is dependent on the choices made by patients, nurses can play an
      emancipatory role by empowering patients with disabilities to become the primary
      agent in their rehabilitation. Objective was to conduct a range analysis protocol
      proposing the mapping of conceptual elements for a nursing care model based on
      the autonomy of disabled persons. METHODS AND ANALYSIS: A protocol was developed
      in corporating insights from recent innovations and applying the scope review
      method of Arksey and O'Malley as a reference using their scoping review
      methodology as a guide. For the construction of research guiding question, the
      patient, intervention, comparison and outcomes strategy was adapted. Considerable
      research in online databases (14) from 2000 to 2018 will be integrated by
      bibliographical research. Proceed a consult in the Annals of the Brazilian
      Congress of Nursing, Brazilian Nursing Association and Portuguese Rehabilitation
      Nursing Association, as well as professional Portuguese and Brazilian nursing
      legislation. The entire reference list of the covered studies searched manually
      to detect considerable additional studies. In addition to these searches,
      stakeholders, including nurse experts in the rehabilitation field and disabled
      persons, will be requested and included. ETHICS AND DISSEMINATION: This study
      does not require ethical approval because it is a review and collection of data
      on publicly available materials. The results of this research will be published
      in a relevant journal on the subject of rehabilitation and presented at
      international scientific events in the area of rehabilitation nursing. Thus, the
      elaboration of this protocol further maps the gaps and strengthens the concepts
      capable of presenting strong evidence which assists and supports safer, smarter
      and more objective care for those living with permanent daily care obligations.

PMID- 30297348
TI  - LDL-C:HDL-C ratio and common carotid plaque in Xinjiang Uygur obese adults: a
      cross-sectional study.
AB  - OBJECTIVE: The aim of this study was to explore the relationship between low
      density lipoprotein cholesterol:high-density lipoprotein cholesterol (LDL-C:HDL
      C) ratio and common carotid atherosclerotic plaque (CCAP) among obese adults of
      Uygur community in Xinjiang, China. DESIGN: A hospital-based cross-sectional
      study. SETTING: First Affiliated Hospital of Xinjiang Medical University.
      PARTICIPANTS: A total of 1449 obese adults of Uygur population who were free of
      coronary artery disease were included in our study from 1 January 2014 to 31
      December 2016. METHODOLOGY: Lipid profiles, other routine laboratory parameters
      and intima-media thickness of the common carotid artery were measured in all
      participants. Multivariate logistic regression analysis was used to examine the
      association between LDL-C:HDL-C ratio and CCAP. RESULTS: Four hundred and fifteen
      (28.64%) participants had CCAP. Participants with CCAP had significantly higher
      LDL-C:HDL-C ratio compared with those without CCAP (3.21 [2.50, 3.88] vs 2.33
      [1.95, 2.97], p<0.001). Multivariate logistic regression analysis showed high LDL
      C:HDL-C ratio as independent predictor of CCAP after adjusting for conventional
      cardiovascular risk factors. The top LDL-C:HDL-C ratio quartile (>=3.25) had an
      OR of 9.355 (95% CI 6.181 to 14.157) compared with the bottom quartile (<2.07) of
      LDL-C:HDL-C ratio (p<0.001) after adjustment for age, body mass index, smoking,
      diabetes mellitus and serum level of total cholesterol. CONCLUSION: CCAP is
      highly prevalent in Uygur obese adults. A high LDL-C:HDL-C ratio is an
      independent predictor of CCAP. It may help identify obese individuals who are at
      high risk of CCAP and who may benefit from intensive LDL-lowering therapy.

PMID- 30297349
TI  - Do changing medical admissions practices in the UK impact on who is admitted? An
      interrupted time series analysis.
AB  - INTRODUCTION: Medical admissions must balance two potentially competing missions:
      to select those who will be successful medical students and clinicians and to
      increase the diversity of the medical school population and workforce. Many
      countries address this dilemma by reducing the heavy reliance on prior
      educational attainment, complementing this with other selection tools. However,
      evidence to what extent this shift in practice has actually widened access is
      conflicting. AIM: To examine if changes in medical school selection processes
      significantly impact on the composition of the student population. DESIGN AND
      SETTING: Observational study of medical students from 18 UK 5-year medical
      programmes who took the UK Clinical Aptitude Test from 2007 to 2014; detailed
      analysis on four schools. PRIMARY OUTCOME: Proportion of admissions to medical
      school for four target groups (lower socioeconomic classes, non-selective
      schooling, non-white and male). DATA ANALYSIS: Interrupted time-series framework
      with segmented regression was used to identify the impact of changes in selection
      practices in relation to invitation to interview to medical school. Four case
      study medical schools were used looking at admissions within for the four target
      groups. RESULTS: There were no obvious changes in the overall proportion of
      admissions from each target group over the 8-year period, averaging at 3.3% lower
      socioeconomic group, 51.5% non-selective school, 30.5% non-white and 43.8% male.
      Each case study school changed their selection practice in decision making for
      invite to interview during 2007-2014. Yet, this within-school variation made
      little difference locally, and changes in admission practices did not lead to any
      discernible change in the demography of those accepted into medical school.
      CONCLUSION: Although our case schools changed their selection procedures, these
      changes did not lead to any observable differences in their student populations.
      Increasing the diversity of medical students, and hence the medical profession,
      may require different, perhaps more radical, approaches to selection.

PMID- 30297350
TI  - Examining the risk of depression or self-harm associated with incretin-based
      therapies used to manage hyperglycaemia in patients with type 2 diabetes: a
      cohort study using the UK Clinical Practice Research Datalink.
AB  - OBJECTIVES: To compare population-based incidence rates of new-onset depression
      or self-harm in patients initiating incretin-based therapies with that of
      sulfonylureas (SU) and other glucose-lowering agents. DESIGN: Population-based
      cohort study. SETTING: Patients attending primary care practices registered with
      the UK-based Clinical Practice Research Datalink (CPRD). PARTICIPANTS: Using the
      UK-based CPRD, we identified two incretin-based therapies cohorts: (1) dipeptidyl
      peptidase-4 inhibitor (DPP-4i)-cohort, consisting of new users of DPP-4i and SU
      and (2) glucagon-like peptide-1 receptor agonists (GLP-1RA)-cohort, consisting of
      new users of GLP-1RA and SU, between January 2007 and January 2016. Patients with
      a prior history of depression, self-harm and other serious psychiatric conditions
      were excluded. MAIN OUTCOME MEASURES: The primary study outcome comprised a
      composite of new-onset depression or self-harm. Unadjusted and adjusted Cox
      proportional hazards regression was used to quantify the association between
      incretin-based therapies and depression or self-harm. Deciles of High-Dimensional
      Propensity Scores and concurrent number of glucose-lowering agents were used to
      adjust for potential confounding. RESULTS: We identified new users of 6206 DPP-4i
      and 22 128 SU in the DPP-4i-cohort, and 501 GLP-1RA and 16 409 SU new users in
      the GLP-1RA-cohort. The incidence of depression or self-harm was 8.2 vs 11.7
      events/1000 person-years in the DPP-4i-cohort and 18.2 vs 13.6 events/1000 person
      years in the GLP-1RA-cohort for incretin-based therapies versus SU, respectively.
      Incretin-based therapies were not associated with an increased or decreased
      incidence of depression or self-harm compared with SU (DPP-4i-cohort: unadjusted
      HR 0.70, 95% CI 0.51 to 0.96; adjusted HR 0.80, 95% CI 0.57 to 1.13; GLP-1RA
      cohort: unadjusted HR 1.36, 95% CI 0.72 to 2.58; adjusted HR 1.25, 95% CI 0.63 to
      2.50). Consistent results were observed for other glucose-lowering comparators
      including insulin and thiazolidinediones. CONCLUSIONS: Our findings suggest that
      the two incretin-based therapies are not associated with an increased or
      decreased risk of depression or self-harm.

PMID- 30297354
TI  - We should scrap the internal market.

PMID- 30297351
TI  - Nutrition and physical performance in older people-effects of marine protein
      hydrolysates to prevent decline in physical performance: a randomised controlled
      trial protocol.
AB  - INTRODUCTION: Age-related loss of muscle mass, muscle strength and muscle
      function (sarcopenia) leads to a decline in physical performance, loss of
      independence and reduced quality of life. Nutritional supplements may delay the
      progression of sarcopenia. The aim of this randomised, double-blinded controlled
      trial including 100 participants (>=65 years) is to assess the effect of a marine
      protein hydrolysate (MPH) on sarcopenia-related outcomes like hand grip strength,
      physical performance or gait speed and to study the associations between physical
      performance and nutritional intake and status. METHOD AND ANALYSIS: The
      intervention group (n=50) will receive 3 g of MPH per day in 12 months. The
      control group (n=50) receive placebo. Assessments of Short Physical Performance
      Battery (SPPB), hand grip strength, anthropometric measurements, nutritional
      status as measured by the Mini Nutritional Assessment, dietary intake, supplement
      use, biomarkers of protein nutrition and vitamin D, and health-related quality of
      life (EQ-5D), will be performed at baseline and after 6 and 12 months of
      intervention. Linear mixed models will be estimated to assess the effect of MPH
      on SPPB, hand grip strength and quality of life, as well as associations between
      physical performance and nutrition. ETHICS AND DISSEMINATION: The study has been
      approved by the Regional Committee in Ethics in Medical Research in Mid-Norway in
      September 2016 with the registration ID 2016/1152. The results will be actively
      disseminated through peer-reviewed journals, conference presentations, social
      media, broadcast media and print media. TRIAL REGISTRATION NUMBER: NCT02890290.

PMID- 30297352
TI  - Efficacy of photobiomodulation on oral lichen planus: a protocol study for a
      double-blind, randomised controlled clinical trial.
AB  - INTRODUCTION: Oral lichen planus (OLP) is an idiopathic chronic mucocutaneous
      disease with a wide range of clinical manifestations, including white reticular
      patches, erosive/ulcerative and atrophic lesions, both associated with intense
      symptomatology. Topical corticosteroids are commonly used as standard therapy.
      However, patients frequently present relapses after the discontinuation of
      treatment as well as developing resistance to corticosteroid therapy.
      Photobiomodulation (PBM) has been shown to be a potential therapeutic tool to
      treat inflammatory disorders, including OLP. The aim of this study was to compare
      the efficacy of PBM (660 nm) with corticosteroid therapy with clobetasol
      propionate 0.05% for the treatment of OLP. METHODS AND ANALYSIS: Forty-four
      patients with symptomatic and histopathological diagnosis of OLP will be
      randomised into two experimental groups in a double-blind manner: control group
      (n=22): clobetasol propionate 0.05%+placebo PBM, and experimental group (n=22):
      PBM (lambda=660 nm, power 100 mW, radiant exposure: 177 J/cm2 and 0.5J per
      point)+placebo gel. Laser will be applied 2*/week for 1 month and clobetasol
      propionate three times a day for 30 days and the same for placebo treatments. The
      primary variable (pain) and the secondary variables (clinical score, evaluation
      of functional scores, clinical resolution, OLP recurrence, quality of life and
      anxiety and depression) will be evaluated at the baseline, once a week during
      treatment (depending on the variables) and after 30 days and 60 days of follow
      up. Pain will be evaluated using visual analogue scale and clinical
      characteristics will be scored using the Thongprasom Index. The quality of life
      and anxiety and depression will be evaluated by Oral Health Impact Profile-14
      questionnaire and by Hospital Anxiety and Depression Scale for anxiety scale,
      respectively. The serum and salivary levels of interleukin (IL)-6, IL-10, IL
      1beta, INF-gamma and tumour necrosis factor-alpha will be evaluated by ELISA at
      baseline and at the end of treatment. ETHICS AND DISSEMINATION: This protocol was
      approved (#2.375.410) by the Nove de Julho University (UNINOVE) Research Ethics
      Committee. The data gathered using this protocol will be published in a peer
      reviewed journal. TRIAL REGISTRATION NUMBER: NCT03320460.

PMID- 30297355
TI  - Cochrane centre based in Spain calls for investigation into director's dismissal.

PMID- 30297353
TI  - Relationship between right-to-left shunt and migraine in patients with epilepsy:
      a single-centre, cross-sectional study in China.
AB  - OBJECTIVES: To investigate the relationship between right-to-left shunt and
      migraine to account for the unexplained high prevalence of migraine in patients
      with epilepsy. DESIGN: This is a cross-sectional study. The diagnosis and
      interview process of patients with migraine was based on the International
      Classification of Headache Disorders-3 beta in patients with epilepsy.
      Participants underwent transthoracic echocardiography (TTE) with contrast medium
      to identify right-to-left shunt. The highest number of microbubbles were recorded
      in the left atrium before the complete microbubble outflow of the right atrium. A
      moderate-to-large shunt was defined as the presence of 10 or more microbubbles.
      SETTING: A single-centre, cross-sectional study in China, 2015-2017.
      PARTICIPANTS: Patients with epilepsy. PRIMARY AND SECONDARY OUTCOME MEASURES: The
      primary outcome measures were the prevalence of migraine, the prevalence of right
      to-left shunt in patients with migraine and those without migraine, and the
      prevalence of migraine in different degrees of shunting. RESULTS: Three hundred
      thirty-nine participants with epilepsy who completed TTE were included in the
      analysis. The overall prevalence of migraine was 23.0%. One-third of the
      migraineurs had mild right-to-left shunt and one-fifth of the migraineurs had
      moderate-to-large right-to-left shunt. Patients with mild shunt did not have a
      higher prevalence of migraine than those without shunt (26.3% vs 18.1%, p=0.102);
      however, a higher prevalence of migraine was found in patients with moderate-to
      large shunt (39.0% vs 18.1%, OR=2.90, 95% CI=1.41 to 5.98, p=0.003). Patients
      with migraine and patients without migraine had similar prevalence of mild shunt;
      however, patients with migraine had more moderate-to-large shunt (20.5% vs 9.6%,
      p=0.002). Right-to-left shunt and female were factors predicting migraine
      prevalence. CONCLUSIONS: One-fifth of migraineurs were correlated with moderate
      to-large right-to-left shunt which could be an underlying cause of migraine in
      epilepsy.

PMID- 30297356
TI  - The Expanding Molecular Genetics Tool Kit in Chlamydia.
AB  - Chlamydia has emerged as an important model system for the study of host pathogen
      interactions, in part due to a resurgence in the development of tools for its
      molecular genetic manipulation. An additional tool, published by Keb et al. (G.
      Keb, R. Hayman, and K. A. Fields, J. Bacteriol. 200:e00479-18, 2018,
      https://doi.org/10.1128/JB.00479-18), now allows for custom genetic engineering
      of genomic regions that were traditionally recalcitrant to genetic manipulation,
      such as genes within operons. This new method will be an essential instrument for
      the elucidation of Chlamydia-host interactions.

PMID- 30297357
TI  - Thermal and Nutritional Regulation of Ribosome Hibernation in Staphylococcus
      aureus.
AB  - The translationally silent 100S ribosome is a poorly understood form of the
      dimeric 70S complex that is ubiquitously found in all bacterial phyla. The
      elimination of the hibernating 100S ribosome leads to translational derepression,
      ribosome instability, antibiotic sensitivity, and biofilm defects in some
      bacteria. In Firmicutes, such as the opportunistic pathogen Staphylococcus
      aureus, a 190-amino acid protein called hibernating-promoting factor (HPF)
      dimerizes and conjoins two 70S ribosomes through a direct interaction between the
      HPF homodimer, with each HPF monomer tethered on an individual 70S complex. While
      the formation of the 100S ribosome in gammaproteobacteria and cyanobacteria is
      exclusively induced during postexponential growth phase and darkness,
      respectively, the 100S ribosomes in Firmicutes are constitutively produced from
      the lag-logarithmic phase through the post-stationary phase. Very little is known
      about the regulatory pathways that control hpf expression and 100S ribosome
      abundance. Here, we show that a general stress response (GSR) sigma factor (SigB)
      and a GTP-sensing transcription factor (CodY) integrate nutrient and thermal
      signals to regulate hpf synthesis in S. aureus, resulting in an enhanced
      virulence of the pathogen in a mouse model of septicemic infection. CodY
      dependent regulation of hpf is strain specific. An epistasis analysis further
      demonstrated that CodY functions upstream of the GSR pathway in a condition
      dependent manner. The results reveal an important link between S. aureus stress
      physiology, ribosome metabolism, and infection biology.IMPORTANCE The
      dimerization of 70S ribosomes (100S complex) plays an important role in
      translational regulation and infectivity of the major human pathogen
      Staphylococcus aureus Although the dimerizing factor HPF has been characterized
      biochemically, the pathways that regulate 100S ribosome abundance remain elusive.
      We identified a metabolite- and nutrient-sensing transcription factor, CodY, that
      serves both as an activator and a repressor of hpf expression in nutrient- and
      temperature-dependent manners. Furthermore, CodY-mediated activation of hpf masks
      a secondary hpf transcript derived from a general stress response SigB promoter.
      CodY and SigB regulate a repertoire of virulence genes. The unexpected link
      between ribosome homeostasis and the two master virulence regulators provides new
      opportunities for alternative druggable sites.

PMID- 30297359
TI  - DNA Damage, Liver Injury, and Tumorigenesis: Consequences of DDX3X Loss.
AB  - The pleiotropic roles of DEAD-box helicase 3, X-linked (DDX3X), including its
      functions in transcriptional and translational regulation, chromosome
      segregation, DNA damage, and cell growth control, have highlighted the
      association between DDX3X and tumorigenesis. However, mRNA transcripts and
      protein levels of DDX3X in patient specimens have shown the controversial
      correlations of DDX3X with hepatocellular carcinoma (HCC) prevalence. In this
      study, generation of hepatocyte-specific Ddx3x-knockout mice revealed that loss
      of Ddx3x facilitates liver tumorigenesis. Loss of Ddx3x led to profound ductular
      reactions, cell apoptosis, and compensatory proliferation in female mutants at 6
      weeks of age. The sustained phosphorylation of histone H2AX (gammaH2AX) and
      significant accumulation of DNA single-strand breaks and double-strand breaks in
      liver indicated that the replicative stress occurred in female mutants. Further
      chromatin immunoprecipitation analyses demonstrated that DDX3X bound to promoter
      regions and regulated the expression of DNA repair factors, DDB2 and XPA, to
      maintain genome stability. Loss of Ddx3x led to decreased levels of DNA repair
      factors, which contributed to an accumulation of unrepaired DNA damage,
      replication stress, and eventually, spontaneous liver tumors and DEN-induced HCCs
      in Alb-Cre/+;Ddx3xflox/flox mice.Implications: These data identify an important
      role of DDX3X in the regulation of DNA damage repair to protect against
      replication stress in liver and HCC development and progression. Mol Cancer Res;
      1-12. (c)2018 AACR.

PMID- 30297358
TI  - Suppression of STING associated with LKB1 loss in KRAS-driven lung cancer.
AB  - KRAS-driven lung cancers frequently inactivate TP53 and/or STK11/LKB1, defining
      tumor subclasses with emerging clinical relevance. Specifically, KRAS-LKB1 (KL)
      mutant lung cancers are particularly aggressive, lack PD-L1, and respond poorly
      to immune checkpoint blockade (ICB). The mechanistic basis for this impaired
      immunogenicity, despite the overall high mutational load of KRAS mutant lung
      cancers, remains obscure. Here we report that LKB1 loss results in marked
      silencing of STING expression and insensitivity to cytoplasmic double strand DNA
      (dsDNA) sensing. This effect is mediated at least in part by hyperactivation of
      DNMT1 and EZH2 activity related to elevated S-adenylmethionine (SAM) levels, and
      reinforced by DNMT1 upregulation. Ectopic expression of STING in KL cells engages
      IRF3 and STAT1 signaling downstream of TBK1 and impairs cellular fitness, due to
      the pathologic accumulation of cytoplasmic mitochondrial dsDNA associated with
      mitochondrial dysfunction. Thus, silencing of STING avoids these negative
      consequences of LKB1 inactivation, while facilitating immune escape.

PMID- 30297360
TI  - Hsp70 binds to the androgen receptor N-terminal domain and modulates the receptor
      function in prostate cancer cells.
AB  - The androgen receptor (AR) is a key driver and therapeutic target in androgen
      sensitive prostate cancer, castration resistant prostate cancer (CRPC), and CRPC
      resistant to abiraterone and enzalutamide, two second generation inhibitors of AR
      signaling. Since current AR inhibitors target a functioning C-terminal ligand
      binding domain (LBD), the identification and characterization of co-factors
      interacting with the N-terminal domain (NTD) of AR may lead to new approaches to
      target AR signaling in CRPC. Using a pulldown approach coupled with proteomics,
      we have identified Hsp70 as a co-factor for the NTD of AR in prostate cancer
      cells. Hsp70 inhibition using siRNA or small molecules indicated that Hsp70
      played an important role in the expression and transactivation of endogenous AR.
      Prostate specific antigen (PSA) promoter/enhancer-driven luciferase assays showed
      that Hsp70 was also required for transactivation of AR mutant lacking LBD.
      Furthermore, clonogenic assays showed that an Hsp70 inhibitor, either alone or in
      synergy with enzalutamide, can inhibit the proliferation of 22Rv1, a widely-used
      enzalutamide-resistant CRPC prostate cancer cell line. These findings suggest
      that Hsp70 is a potential therapeutic target for the treatment of enzalutamide
      resistant CRPC.

PMID- 30297361
TI  - Oleanolic acid inhibits epithelial-mesenchymal transition of hepatocellular
      carcinoma by promoting iNOS dimerization.
AB  - Oleanolic acid (OA) exhibits extensive pharmacological activities and takes
      significant anti-tumor effects. Its pharmacological mechanism, however, are still
      remained to be further clarified. In this study, we demonstrated that OA
      attenuated the migration and invasion abilities, resulting in the suppression of
      the EMT process in liver cancer cells, and inhibited the tumor growth of the PLC
      bearing mice. We further proved that inducible nitric oxide synthase (iNOS) may
      be the potential target of OA. We confirmed that OA could promote the
      dimerization of iNOS, activating it and subsequently increasing the production of
      nitric oxide (NO). Further experiments indicated that OA promoted the nitration
      of specific proteins and consequently suppressed their epithelial-mesenchymal
      transition (EMT)-related biological functions. Furthermore, it has been confirmed
      that OA enhanced the anti-tumor effects of regorafenib in liver cancer treatment.
      These results deepened our understanding of the pharmacological mechanism of the
      antitumor effect OA, and the importance of NOS as a therapeutic target for liver
      cancer treatment.

PMID- 30297362
TI  - Role of Capsule in Resistance to Disinfectants, Host Antimicrobials, and
      Desiccation in Acinetobacter baumannii.
AB  - Acinetobacter baumannii strain AB5075 forms two cell types distinguished by their
      opaque (VIR-O) or translucent (AV-T) colonies. VIR-O cells possess a thicker
      capsule and are more resistant to a variety of stressors than AV-T cells.
      However, the direct role of the capsule in these stressors was unknown. This
      study demonstrates that the capsule is required for resistance to disinfectants,
      lysozyme, and desiccation in Acinetobacter baumannii In addition, the capsule is
      required for survival in a mouse lung model of infection.

PMID- 30297363
TI  - Polymorphism of Polymeric Amino Acid Regions in Fungal Proteins and Correlation
      with Altered Echinocandin and Azole Susceptibility.
AB  - Polymorphism of polymeric amino acid (polyX) regions within fungal proteins
      represents a potential mechanism for rapid genotypic adaptation to environmental
      pressures, including antifungal exposure. Polyglutamine (polyQ) was the most
      abundant repeat in the proteomes of 8 diverse fungal species and was
      preferentially found in regulatory proteins. In Candida glabrata, polyX
      polymorphisms were characterized in 36 proteins implicated in azole or
      echinocandin susceptibility. General transcriptional repressor Tup1A exhibited
      Q44/Q45 polymorphism, and Hog1 signaling component Ssk2 exhibited N44/N45
      polymorphism in phylogenetically matched echinocandin- and azole
      susceptible/resistant strains, respectively.

PMID- 30297364
TI  - Two Regulators, PA3898 and PA2100, Modulate the Pseudomonas aeruginosa Multidrug
      Resistance MexAB-OprM and EmrAB Efflux Pumps and Biofilm Formation.
AB  - It is generally believed that the Pseudomonas aeruginosa biofilm matrix itself
      acts as a molecular sieve or sink that contributes to significant levels of drug
      resistance, but it is becoming more apparent that multidrug efflux pumps induced
      during biofilm growth significantly enhance resistance levels. We present here a
      novel transcriptional regulator, PA3898, which controls biofilm formation and
      multidrug efflux pumps in P. aeruginosa A mutant of this regulator significantly
      reduced the ability of P. aeruginosa to produce biofilm in vitro and affected its
      in vivo fitness and pathogenesis in Drosophila melanogaster and BALB/c mouse lung
      infection models. Transcriptome analysis revealed that PA3898 modulates essential
      virulence genes/pathways, including multidrug efflux pumps and phenazine
      biosynthesis. Chromatin immunoprecipitation sequencing (ChIP-seq) identified its
      DNA binding sequences and confirmed that PA3898 directly interacts with promoter
      regions of four genes/operons, two of which are mexAB-oprM and phz2
      Coimmunoprecipitation revealed a regulatory partner of PA3898 as PA2100, and both
      are required for binding to DNA in electrophoretic mobility shift assays. PA3898
      and PA2100 were given the names MdrR1 and MdrR2, respectively, as novel
      repressors of the mexAB-oprM multidrug efflux operon and activators for another
      multidrug efflux pump, EmrAB. The interaction between MdrR1 and MdrR2 at the
      promoter regions of their regulons was further characterized via localized
      surface plasmon resonance and DNA footprinting. These regulators directly repress
      the mexAB-oprM operon, independent of its well-established MexR regulator.
      Mutants of mdrR1 and mdrR2 caused increased resistance to multiple antibiotics in
      P. aeruginosa, validating the significance of these newly discovered regulators.

PMID- 30297365
TI  - Breaking the Vicious Cycle of Antibiotic Killing and Regrowth of Biofilm-Residing
      Pseudomonas aeruginosa.
AB  - Biofilm-residing bacteria embedded in an extracellular matrix are protected from
      diverse physicochemical insults. In addition to the general recalcitrance of
      biofilm bacteria, high bacterial loads in biofilm-associated infections
      significantly diminish the efficacy of antimicrobials due to a low per-cell
      antibiotic concentration. Accordingly, present antimicrobial treatment protocols
      that have been established to serve the eradication of acute infections fail to
      clear biofilm-associated chronic infections. In the present study, we applied
      automated confocal microscopy on Pseudomonas aeruginosa to monitor dynamic
      killing of biofilm-grown bacteria by tobramycin and colistin in real time. We
      revealed that the time required for surviving bacteria to repopulate the biofilm
      could be taken as a measure for effectiveness of the antimicrobial treatment. It
      depends on the (i) nature and concentration of the antibiotic, (ii) duration of
      antibiotic treatment, (iii) application as monotherapy or combination therapy,
      and (iv) interval of drug administration. The vicious cycle of killing and
      repopulation of biofilm bacteria could also be broken in an in vivo model system
      by applying successive antibiotic dosages at intervals that do not allow full
      reconstitution of the biofilm communities. Treatment regimens that consider the
      important aspects of antimicrobial killing kinetics bear the potential to improve
      control of biofilm regrowth. This is an important and underestimated factor that
      is bound to ensure sustainable treatment success of chronic infections.

PMID- 30297366
TI  - Competitive Fitness of Essential Gene Knockdowns Reveals a Broad-Spectrum
      Antibacterial Inhibitor of the Cell Division Protein FtsZ.
AB  - To streamline the elucidation of antibacterial compounds' mechanism of action,
      comprehensive high-throughput assays interrogating multiple putative targets are
      necessary. However, current chemogenomic approaches for antibiotic target
      identification have not fully utilized the multiplexing potential of next
      generation sequencing. Here, we used Illumina sequencing of transposon insertions
      to track the competitive fitness of a Burkholderia cenocepacia library containing
      essential gene knockdowns. Using this method, we characterized a novel
      benzothiadiazole derivative, 10126109 (C109), with antibacterial activity against
      B. cenocepacia, for which whole-genome sequencing of low-frequency spontaneous
      drug-resistant mutants had failed to identify the drug target. By combining the
      identification of hypersusceptible mutants and morphology screening, we show that
      C109 targets cell division. Furthermore, fluorescence microscopy of bacteria
      harboring green fluorescent protein (GFP) cell division protein fusions revealed
      that C109 prevents divisome formation by altering the localization of the
      essential cell division protein FtsZ. In agreement with this, C109 inhibited both
      the GTPase and polymerization activities of purified B. cenocepacia FtsZ. C109
      displayed antibacterial activity against Gram-positive and Gram-negative cystic
      fibrosis pathogens, including Mycobacterium abscessus C109 effectively cleared B.
      cenocepacia infection in the Caenorhabditis elegans model and exhibited additive
      interactions with clinically relevant antibiotics. Hence, C109 is an enticing
      candidate for further drug development.

PMID- 30297368
TI  - Amixicile Reduces Severity of Cryptosporidiosis but Does Not Have In Vitro
      Activity against Cryptosporidium.
AB  - Cryptosporidium species cause significant morbidity in malnourished children.
      Nitazoxanide (NTZ) is the only approved treatment for cryptosporidiosis, but NTZ
      has diminished effectiveness during malnutrition. Here, we show that amixicile, a
      highly selective water-soluble derivative of NTZ diminishes Cryptosporidium
      infection severity in a malnourished mouse model despite a lack of direct
      anticryptosporidial activity. We suggest that amixicile, by tamping down
      anaerobes associated with intestinal inflammation, reverses weight loss and
      indirectly mitigates infection-associated pathology.

PMID- 30297367
TI  - Lipase Precursor-Like Protein Promotes Miltefosine Tolerance in Leishmania
      donovani by Enhancing Parasite Infectivity and Eliciting Anti-inflammatory
      Responses in Host Macrophages.
AB  - The oral drug miltefosine (MIL) was introduced in the Indian subcontinent in the
      year 2002 for the treatment of visceral leishmaniasis (VL). However, recent
      reports on its declining efficacy and increasing relapse rates pose a serious
      concern. An understanding of the factors contributing to MIL tolerance in
      Leishmania parasites is critical. In the present study, we assessed the role of
      the lipase precursor-like protein (Lip) in conferring tolerance to miltefosine by
      episomally overexpressing Lip in Leishmania donovani (LdLip++). We observed a
      significant increase (~3-fold) in the MIL 50% inhibitory concentration (IC50) at
      both the promastigote (3.90 +/- 0.68 uM; P < 0.05) and intracellular amastigote
      (9.10 +/- 0.60 uM; P < 0.05) stages compared to the wild-type counterpart (LdNeo)
      (MIL IC50s of 1.49 +/- 0.20 uM at the promastigote stage and 3.95 +/- 0.45 uM at
      the amastigote stage). LdLip++ parasites exhibited significantly (P < 0.05)
      increased infectivity to host macrophages and increased metacyclogenesis and
      tolerance to MIL-induced oxidative stress. The susceptibility of LdLip++ to other
      antileishmanial drugs (sodium antimony gluconate and amphotericin B) remained
      unchanged. In comparison to LdNeo, the LdLip++ parasites elicited high host
      interleukin-10 (IL-10) cytokine expression levels (1.6-fold; P < 0.05) with
      reduced expression of the cytokine tumor necrosis factor alpha (TNF-alpha) (1.5
      fold; P < 0.05), leading to a significantly (P < 0.01) increased ratio of IL
      10/TNF-alpha. The above-described findings suggest a role of lipase precursor
      like protein in conferring tolerance to the oral antileishmanial drug MIL in L.
      donovani parasites.

PMID- 30297369
TI  - Effects of Food and Omeprazole on a Novel Formulation of Super Bioavailability
      Itraconazole in Healthy Subjects.
AB  - To address the limited bioavailability and intolerance of the conventional
      itraconazole (ITZ) formulations, a new formulation labeled super bioavailability
      (SUBA) itraconazole has been developed; however, the specific effects of food and
      gastric pH are unknown. This study evaluated the pharmacokinetic profile of SUBA
      itraconazole under fasting and fed conditions, as well as with the concomitant
      administration of a proton pump inhibitor. First, the effect of food was assessed
      in an open-label, randomized, crossover bioavailability study of 65-mg SUBA
      itraconazole capsules (2 65-mg capsules twice a day) in healthy adults (n = 20)
      under fasting and fed conditions to steady-state levels. Second, an open-label,
      two-treatment, fixed-sequence comparative bioavailability study in healthy adults
      (n = 28) under fasted conditions compared the pharmacokinetics of a single oral
      dose of SUBA itraconazole capsules (2 65-mg capsules/day) with and without
      coadministration of daily omeprazole delayed-release capsules (1 40-mg
      capsule/day) under steady-state conditions. In the fed and fasted states, SUBA
      itraconazole demonstrated similar concentrations at the end of the dosing
      interval, with modestly lower total and peak ITZ exposure being shown when it was
      administered under fed conditions than when it was administered in the fasted
      state, with fed state/fasted state ratios of 78.09% (90% confidence interval
      [CI], 74.49 to 81.86%) for the area under the concentration-time curve over the
      dosing interval (14,183.2 versus 18,479.8 ng . h/ml), 73.05% (90% CI, 69.01 to
      77.33%) for the maximum concentration at steady state (1,519.1 versus 2,085.2
      ng/ml), and 91.53% (90% CI, 86.41 to 96.96%) for the trough concentration
      (1,071.5 versus 1,218.5 ng/ml) being found. When dosed concomitantly with
      omeprazole, there was a 22% increase in the total plasma exposure of ITZ, as
      measured by the area under the concentration-time curve from time zero to
      infinity (P = 0.0069), and a 31% increase in the peak plasma exposure of ITZ, as
      measured by the maximum concentration (P = 0.0083).

PMID- 30297370
TI  - Molecular Basis of the Leishmanicidal Activity of the Antidepressant Sertraline
      as a Drug Repurposing Candidate.
AB  - Drug repurposing affords the implementation of new treatments at a moderate cost
      and under a faster time-scale. Most of the clinical drugs against Leishmania
      share this origin. The antidepressant sertraline has been successfully assayed in
      a murine model of visceral leishmaniasis. Nevertheless, sertraline targets in
      Leishmania were poorly defined. In order to get a detailed insight into the
      leishmanicidal mechanism of sertraline on Leishmania infantum, unbiased
      multiplatform metabolomics and transmission electron microscopy were combined
      with a focused insight into the sertraline effects on the bioenergetics
      metabolism of the parasite. Sertraline induced respiration uncoupling, a
      significant decrease of intracellular ATP level, and oxidative stress in L.
      infantum promastigotes. Metabolomics evidenced an extended metabolic disarray
      caused by sertraline. This encompasses a remarkable variation of the levels of
      thiol-redox and polyamine biosynthetic intermediates, as well as a shortage of
      intracellular amino acids used as metabolic fuel by Leishmania Sertraline killed
      Leishmania through a multitarget mechanism of action, tackling essential
      metabolic pathways of the parasite. As such, sertraline is a valuable candidate
      for visceral leishmaniasis treatment under a drug repurposing strategy.

PMID- 30297371
TI  - Unilateral leg swelling in an infant.
AB  - : An 8-month-old boy presented with a week's history of left lower limb swelling.
      He was apyrexic, well and developmentally age appropriate. He was born at 35+5
      via by C-section for breech presentation, weighing 3.47 kg (97th centile).His
      left calf measured 21.5 cm and the right calf 19.5 cm. The overlying skin showed
      mild eczema. There was no circulatory compromise of the left leg, and he was
      systemically well.X-rays of the left tibia and fibula were normal. He received
      oral antibiotics for presumed cellulitis. A follow-up showed some improvement
      (figure 1). A subsequent Doppler ultrasound of the left leg was normal.
      edpract;archdischild-2018-315527v1/F1F1F1Figure 1Appearance of both calves at age
      10 months.He continued to show size variation of the calf (figure 2). A pit on
      the helix of left ear and a faded haemangioma over left eyelid were noted.
      edpract;archdischild-2018-315527v1/F2F2F2Figure 2Appearance of both calves at age
      15 months.Blood investigations including full blood count, C reactive protein,
      electrolytes, muscle enzymes (CK), liver, thyroid, bone profile, alpha feto
      protein and insulin-like growth factor 1 were normal. Abdominal scan was normal.
      QUESTIONS: What is the most likely diagnosis? CellulitisPerlman syndromeSotos
      syndromeBeckwith-Wiedemann syndrome (BWS)Simpson-Golabi-Behmel syndromeDeep
      venous thrombosis (DVT) What should we do next?How would you manage the
      condition?What are the complications associated with this condition? Answers can
      be found on page 2.

PMID- 30297372
TI  - Assessing the advertisement of waterpipe tobacco on eBay in the UK.

PMID- 30297373
TI  - Population Assessment of Tobacco and Health (PATH) reliability and validity
      study: selected reliability and validity estimates.
AB  - INTRODUCTION: This paper reports a study done to estimate the reliability and
      validity of answers to the Youth and Adult questionnaires of the Population
      Assessment of Tobacco and Health (PATH) Study. METHODS: 407 adults and 117 youth
      respondents completed the wave 4 (2016-2017) PATH Study interview twice, 6-24
      days apart. The reinterview data were used to estimate the reliability of answers
      to the questionnaire. Kappa statistics, gross discrepancy rates and correlations
      between answers to the initial interview and the reinterview were used to measure
      reliability. We examined every item in the questionnaire for which there were at
      least 100 observations. After the reinterview, most respondents provided a saliva
      sample that allowed us to assess the accuracy of their answers to the tobacco use
      questions. RESULTS: There was generally a very high level of agreement between
      answers in the interview and reinterview. On the key current tobacco use items,
      the average kappa (the agreement rate adjusted for chance agreement) was 0.79 for
      adult respondents (age 18 or older). Youth respondents exhibited equally high
      levels of agreement across interviews. The items on current tobacco use also
      exhibited high levels of agreement with saliva test results (kappa=0.72). Rating
      scale items showed lower levels of exact agreement across interviews but the
      answers were generally within one scale point or category. CONCLUSIONS: The PATH
      Study questions were developed using a careful protocol and the results indicate
      the answers provide reliable and valid information about tobacco use.

PMID- 30297374
TI  - The Ric-8A/Galpha13/FAK signalling cascade controls focal adhesion formation
      during neural crest cell migration in Xenopus.
AB  - Ric-8A is a pleiotropic guanine nucleotide exchange factor involved in the
      activation of various heterotrimeric G-protein pathways during adulthood and
      early development. Here, we sought to determine the downstream effectors of Ric
      8A during the migration of the vertebrate cranial neural crest (NC) cells. We
      show that the Galpha13 knockdown phenocopies the Ric-8A morphant condition,
      causing actin cytoskeleton alteration, protrusion instability, and a strong
      reduction in the number and dynamics of focal adhesions. In addition, the
      overexpression of Galpha13 is sufficient to rescue Ric-8A-depleted cells. Ric-8A
      and Galpha13 physically interact and colocalize in protrusions of the cells
      leading edge. The focal adhesion kinase FAK colocalizes and interacts with the
      endogenous Galpha13, and a constitutively active form of Src efficiently rescues
      the Galpha13 morphant phenotype in NC cells. We propose that Ric-8A-mediated
      Galpha13 signalling is required for proper cranial NC cell migration by
      regulating focal adhesion dynamics and protrusion formation.

PMID- 30297375
TI  - Effectiveness of a multistate quality improvement campaign in reducing risk of
      surgical site infections following hip and knee arthroplasty.
AB  - BACKGROUND: Quality improvement (QI) campaigns appear to increase use of evidence
      based practices, but their effect on health outcomes is less well studied.
      OBJECTIVE: To assess the effect of a multistate QI campaign (Project JOINTS,
      Joining Organizations IN Tackling SSIs) that used the Institute for Healthcare
      Improvement's Rapid Spread Network to promote adoption of evidence-based surgical
      site infection (SSI) prevention practices. METHODS: We analysed rates of SSI
      among Medicare beneficiaries undergoing hip and knee arthroplasty during
      preintervention (May 2010 to April 2011) and postintervention (November 2011 to
      September 2013) periods in five states included in a multistate trial of the
      Project JOINTS campaign and five matched comparison states. We used generalised
      linear mixed effects models and a difference-in-differences approach to estimate
      changes in SSI outcomes. RESULTS: 125 070 patients underwent hip arthroplasty in
      405 hospitals in intervention states, compared with 131 787 in 525 hospitals in
      comparison states. 170 663 patients underwent knee arthroplasty in 397 hospitals
      in intervention states, compared with 196 064 in 518 hospitals in comparison
      states. After the campaign, patients in intervention states had a 15% lower odds
      of developing hip arthroplasty SSIs (OR=0.85, 95% CI 0.75 to 0.96, p=0.01) and a
      12% lower odds of knee arthroplasty SSIs than patients in comparison states
      (OR=0.88, 95% CI 0.78 to 0.99, p=0.04). CONCLUSIONS: A larger reduction of SSI
      rates following hip and knee arthroplasty was shown in intervention states than
      in matched control states.

PMID- 30297376
TI  - Mortality alerts, actions taken and declining mortality: true effect or
      regression to the mean?

PMID- 30297377
TI  - National hospital mortality surveillance system: a descriptive analysis.
AB  - OBJECTIVE: To provide a description of the Imperial College Mortality
      Surveillance System and subsequent investigations by the Care Quality Commission
      (CQC) in National Health Service (NHS) hospitals receiving mortality alerts.
      BACKGROUND: The mortality surveillance system has generated monthly mortality
      alerts since 2007, on 122 individual diagnosis and surgical procedure groups,
      using routinely collected hospital administrative data for all English acute NHS
      hospital trusts. The CQC, the English national regulator, is notified of each
      alert. This study describes the findings of CQC investigations of alerting
      trusts. METHODS: We carried out (1) a descriptive analysis of alerts (2007-2016)
      and (2) an audit of CQC investigations in a subset of alerts (2011-2013).
      RESULTS: Between April 2007 and October 2016, 860 alerts were generated and 76%
      (654 alerts) were sent to trusts. Alert volumes varied over time (range: 40-101).
      Septicaemia (except in labour) was the most commonly alerting group (11.5% alerts
      sent). We reviewed CQC communications in a subset of 204 alerts from 96 trusts.
      The CQC investigated 75% (154/204) of alerts. In 90% of these pursued alerts,
      trusts returned evidence of local case note reviews (140/154). These reviews
      found areas of care that could be improved in 69% (106/154) of alerts. In 25%
      (38/154) trusts considered that identified failings in care could have impacted
      on patient outcomes. The CQC investigations resulted in full trust action plans
      in 77% (118/154) of all pursued alerts. CONCLUSION: The mortality surveillance
      system has generated a large number of alerts since 2007. Quality of care
      problems were found in 69% of alerts with CQC investigations, and one in four
      trusts reported that failings in care may have an impact on patient outcomes.
      Identifying whether mortality alerts are the most efficient means to highlight
      areas of substandard care will require further investigation.

PMID- 30297378
TI  - EHR-related alert fatigue: minimal progress to date, but much more can be done.

PMID- 30297379
TI  - Knowledge translation facilitating co-creation of evidence in public health.

PMID- 30297380
TI  - Mental health service made available to all doctors in England.

PMID- 30297382
TI  - A European Whitefish Linkage Map and Its Implications for Understanding Genome
      Wide Synteny Between Salmonids Following Whole Genome Duplication.
AB  - Genomic datasets continue to increase in number due to the ease of production for
      a wider selection of species including non-model organisms. For many of these
      species, especially those with large or polyploid genomes, highly contiguous and
      well-annotated genomes are still rare due to the complexity and cost involved in
      their assembly. As a result, a common starting point for genomic work in non
      model species is the production of a linkage map. Dense linkage maps facilitate
      the analysis of genomic data in a variety of ways, from broad scale observations
      regarding genome structure e.g. chromosome number and type or sex-related
      structural differences, to fine scale patterns e.g. recombination rate variation
      and co-localization of differentiated regions. Here we present both sex-averaged
      and sex-specific linkage maps for Coregonus sp. "Albock", a member of the
      European whitefish lineage (C. lavaretus spp. complex), containing 5395 single
      nucleotide polymorphism (SNP) loci across 40 linkage groups to facilitate future
      investigation into the genomic basis of whitefish adaptation and speciation. The
      map was produced using restriction-site associated digestion (RAD) sequencing
      data from two wild-caught parents and 156 F1 offspring. We discuss the
      differences between our sex-averaged and sex-specific maps and identify genome
      wide synteny between C. sp. "Albock" and Atlantic Salmon (Salmo salar), which
      have diverged following the salmonid-specific whole genome duplication. Our
      analysis confirms that many patterns of synteny observed between Atlantic Salmon
      and Oncorhynchus and Salvelinus species are also shared by members of the
      Coregoninae subfamily. We also show that regions known for their species-specific
      rediploidization history can pose challenges for synteny identification since
      these regions have diverged independently in each salmonid species following the
      salmonid-specific whole genome duplication. The European whitefish map provided
      here will enable future studies to understand the distribution of loci of
      interest, e.g. FST outliers, along the whitefish genome as well as assisting with
      the de novo assembly of a whitefish reference genome.

PMID- 30297383
TI  - The Caenorhabditis elegans Oxidative Stress Response Requires the NHR-49
      Transcription Factor.
AB  - The overproduction of reactive oxygen species (ROS) in cells can lead to the
      development of diseases associated with aging. We have previously shown that C.
      elegans BRAP-2 (Brca-1 associated binding protein 2) regulates phase II
      detoxification genes such as gst-4, by increasing SKN-1 activity. Previously, a
      transcription factor (TF) RNAi screen was conducted to identify potential
      activators that are required to induce gst-4 expression in brap-2(ok1492)
      mutants. The lipid metabolism regulator NHR-49/HNF4 was among 18 TFs identified.
      Here, we show that knockdown of nhr-49 suppresses the activation of gst-4 caused
      by brap-2 inactivation and that gain-of-function alleles of nhr-49 promote gst-4
      expression. We also demonstrate that nhr-49 and its cofactor mdt-15 are required
      to express phase II detoxification enzymes upon exposure to chemicals that induce
      oxidative stress. Furthermore, we show that NHR-49 and MDT-15 enhance expression
      of skn-1a/c These findings identify a novel role for NHR-49 in ROS detoxification
      by regulating expression of SKN-1C and phase II detoxification genes.

PMID- 30297384
TI  - Clinical Benefit to an Aurora A Kinase Inhibitor in a Patient with Metastatic
      Integrase Interactor 1-Deficient Carcinoma.
AB  - : Integrase interactor 1 (INI-1)-deficient carcinoma is a rare cancer
      characterized by the loss of the SWItch/Sucrose Non-Fermentable-related matrix
      associated actin-dependent regulator of chromatin subfamily B member 1 gene
      (SMARCB1) and tends to follow an aggressive clinical course. There is no
      currently available standard therapy option, although a few promising treatment
      strategies, including enhancer of zeste homolog 2 (EZH2) inhibition, are under
      active investigation. This report describes a 30-year-old woman with INI-1
      deficient carcinoma who progressed on combination chemotherapy and an EZH2
      inhibitor. Next-generation-sequencing-based targeted cancer-related gene assay
      confirmed SMARCB1 loss and revealed other mutations in breast cancer 1 gene and
      checkpoint kinase 2 gene, which may have impacted her clinical course. After
      discussion at the molecular tumor board, she was offered alisertib, an aurora A
      kinase inhibitor, on a single-patient expanded-use program and achieved prolonged
      disease stabilization. Aurora A kinase inhibition may have an important role in
      the management of patients with INI-1-deficient tumors, warranting further
      evaluation in clinical studies. KEY POINTS: Loss of the SWItch/Sucrose Non
      Fermentable-related matrix-associated actin-dependent regulator of chromatin
      subfamily B member 1 gene (SMARCB1), which encodes integrase interactor 1 (INI
      1), is associated with various mesenchymal malignancies, but a few carcinomas
      with rhabdoid features have been recently described as a distinct entity.INI-1
      deficient carcinoma can be very aggressive, and there is no known treatment
      option available.There are encouraging preliminary data with an enhancer of zeste
      homolog 2 inhibitor, tazematostat, in INI-1-deficient malignancies, including INI
      1-deficient carcinomas.Loss of INI-1 can activate aurora A kinase (AurkA), and
      inhibition of AurkA by alisertib could be a viable option and warrants further
      investigation in this cancer.Clinical genomic profiling can confirm diagnosis of
      molecularly defined malignancy and provide insights on therapeutic options.

PMID- 30297386
TI  - Indirect Evaluation of Bone Saturation with Zoledronic Acid After Long-Term
      Dosing.
AB  - BACKGROUND: Zoledronic acid (ZA), a potent bisphosphonate used for treatment of
      bone metastasis, has high bone affinity. This post hoc analysis evaluated the
      effects of long-term treatment and reduction in dosing frequency of ZA on bone
      saturation. MATERIALS AND METHODS: Pharmacokinetic data from three independent
      studies, OPTIMIZE-2 (patients receiving >=9 doses of bisphosphonates) and two
      phase I studies, CZOL4460503 and CZOL4460506 (patients who were bisphosphonate
      naive/bisphosphonate free for >=1 year after previous dosing), were pooled.
      Serial urine and plasma samples were used as surrogate markers to determine ZA
      plasma area under the curve (AUC) over 6 hours (AUC0-6h) and dose excreted in
      urine over 6 hours (urine0-6h). Potential relationships between the number of
      years for which patients had been treated previously at time of study entry and
      AUC0-6h or urine0-6h were analyzed graphically. RESULTS: Creatinine clearances
      for patients were similar across the three studies and at all time points
      analyzed. The levels of AUC0-6h ZA in plasma at week 0 in every (q) 4 and q12
      weekly arms of OPTIMIZE-2 were 0.366 h * mg/L and 0.397 h * mg/L compared with
      0.345 h * mg/L and 0.356 h * mg/L in CZOL4460503 and CZOL4460506, respectively.
      In OPTIMIZE-2, the AUC0-6h ZA plasma levels were the same (0.428 h * mg/L) at
      week 36 in both q4 and q12 arms. The levels of ZA urine0-6h at week 36 in
      OPTIMIZE-2 (q4 and q12 week arms), CZOL4460503, and CZOL4460506 were 36.6%,
      30.8%, 26.5%, and 27.3%, respectively. CONCLUSION: Long-term ZA treatment may not
      impact bone saturation, and ZA dosing frequency does not seem to influence drug
      retention rates. IMPLICATIONS FOR PRACTICE: Zoledronic acid (ZA), used along with
      standard antineoplastic therapy to treat bone metastases associated with solid
      tumors and multiple myeloma, requires frequent (every 3-4 or every 12 weeks) long
      term administration. This may result in bone saturation and subsequently lead to
      a higher risk of adverse events such as osteonecrosis of the jaw and atypical
      fractures. This post hoc analysis used surrogate markers to demonstrate that
      prolonged ZA administration does not cause bone saturation. Furthermore,
      reduction in ZA dosing frequency does not affect its retention level in bones
      over time. These findings will help in addressing clinicians' concerns regarding
      prolonged ZA administration.

PMID- 30297387
TI  - Five minutes with . . . Terry Kemple on the Green Impact for Health toolkit.

PMID- 30297385
TI  - Phase I/II Trial of Vandetanib and Bortezomib in Adults with Locally Advanced or
      Metastatic Medullary Thyroid Cancer.
AB  - LESSONS LEARNED: Vandetanib at a dose of 300 mg orally every day plus bortezomib
      1.3 mg/m2 intravenously on days 1, 4, 8, and 11 could be administered
      safely.Assessing outcomes in 17 patients with medullary thyroid cancer,
      investigators considered the combination to be more difficult to administer than
      single-agent vandetanib and that achieving better outcomes was unlikely.
      Consequently, a planned phase II study was terminated early. BACKGROUND: The
      proto-oncogene RET (REarranged during Transfection) has a critical role in the
      pathogenesis of medullary thyroid cancer (MTC). Vandetanib (V), a multitargeted
      tyrosine kinase inhibitor approved for the treatment of MTC, is thought to
      inhibit RET in MTC. Supported by preclinical studies demonstrating that
      bortezomib (B) administration lowered RET mRNA and protein levels, we conducted a
      phase I study in advanced solid tumors of vandetanib in combination with
      bortezomib. The goal was to establish an RP2D (recommended phase II dose) for the
      combination of vandetanib plus bortezomib, a regimen envisioned as a dual
      strategy for targeting RET in MTC. METHODS: Patients with advanced solid tumors
      were treated with escalating doses of bortezomib or vandetanib to assess the
      safety and tolerability of daily oral vandetanib and intravenous (IV) bortezomib
      administered on days 1, 4, 8, and 11 of a 28-day cycle. Intrapatient dose
      escalation was allowed. RESULTS: Twenty-two patients were enrolled and received
      escalating mg/m2 bortezomib and mg vandetanib (number of patients) at initial
      doses of 1 and 100 (3), 1.3 and 100 (6), 1.3 and 200 (6), and 1.3 and 300 (7),
      respectively. Patients received a median of four cycles of bortezomib/vandetanib
      (range: 1-10), with 13 patients escalating to 1.3/200 and 10 to 1.3/300. G3
      toxicities occurring in more than one patient included hypertension (24%),
      fatigue (19%), thrombocytopenia (10%), diarrhea (10%), and arthralgia (10%).
      There were no drug-related G4/5 toxicities. There was one dose-limiting toxicity,
      G3 thrombocytopenia, at bortezomib/vandetanib doses of 1.3/200 in cycle 2 that
      resolved without intervention. Four patients with a diagnosis of MTC (27%) had a
      partial response (PR). CONCLUSION: The MTD of the combination was established as
      bortezomib, 1.3 mg/m2 IV days 1, 4, 8, and 11 with vandetanib 300 mg p.o. daily.
      RECIST responses were observed in patients with a diagnosis of MTC.

PMID- 30297388
TI  - Excess deaths: government review should include the use of occupied bed space.

PMID- 30297390
TI  - Prostate cancer aggressiveness and age: Impact of p53, BCL-2 and microvessel
      density.
AB  - Older men are more likely to have advanced prostate cancer at time of their
      diagnosis, but whether prostate tumors are inherently (biologically) more
      aggressive with advancing age is uncertain. To address this gap in knowledge, we
      analyzed data from veterans (n=971) diagnosed with prostate cancer during 1991
      1995. Factors included age, detection of prostate cancer by screening, prostate
      specific antigen (PSA) level, anatomic stage, and Gleason score. Information on
      molecular markers obtained from immunohistochemical staining of prostate tissue,
      included B cell lymphoma-2 (bcl-2), p53, and microvessel density (MVD), each
      having a previously documented association with disease progression and increased
      risk of prostate cancer death. We first examined the bivariate association of
      demographic, clinical, and molecular factors with age, and found evidence that
      race, screening status, Gleason score, PSA, bcl-2, p53, and MVD varied across
      categories of age in this study population. After further characterizing the
      association between age and Gleason score, we used logistic regression to examine
      the association between age and molecular markers-accounting for race, screening
      status, PSA, and Gleason score. Comparing men older than 80 years to those
      younger than 70 years, adjusted ORs and 95% CIs were 1.89 (0.73 to 4.92), 1.91
      (1.05 to 3.46), and 2.00 (1.06 to 3.78), for positive bcl-2, p53, and MVD
      markers, respectively; no statistically significant associations were found for
      men 70-79 years old, compared with men younger than 70 years. These novel
      findings suggest that very elderly men often present with biologically aggressive
      prostate cancer; the results also have potential implications for therapeutic
      decision-making.

PMID- 30297391
TI  - The low but uncertain measured benefits of US water quality policy.
AB  - US investment to decrease pollution in rivers, lakes, and other surface waters
      has exceeded $1.9 trillion since 1960, and has also exceeded the cost of most
      other US environmental initiatives. These investments come both from the 1972
      Clean Water Act and the largely voluntary efforts to control pollution from
      agriculture and urban runoff. This paper reviews the methods and conclusions of
      about 20 recent evaluations of these policies. Surprisingly, most analyses
      estimate that these policies' benefits are much smaller than their costs; the
      benefit-cost ratio from the median study is 0.37. However, existing evidence is
      limited and undercounts many types of benefits. We conclude that it is unclear
      whether many of these regulations truly fail a benefit-cost test or whether
      existing evidence understates their net benefits; we also describe specific
      questions that when answered would help eliminate this uncertainty.

PMID- 30297389
TI  - Kinesin-binding-triggered conformation switching of microtubules contributes to
      polarized transport.
AB  - Kinesin-1, the founding member of the kinesin superfamily of proteins, is known
      to use only a subset of microtubules for transport in living cells. This biased
      use of microtubules is proposed as the guidance cue for polarized transport in
      neurons, but the underlying mechanisms are still poorly understood. Here, we
      report that kinesin-1 binding changes the microtubule lattice and promotes
      further kinesin-1 binding. This high-affinity state requires the binding of
      kinesin-1 in the nucleotide-free state. Microtubules return to the initial low
      affinity state by washing out the binding kinesin-1 or by the binding of non
      hydrolyzable ATP analogue AMPPNP to kinesin-1. X-ray fiber diffraction,
      fluorescence speckle microscopy, and second-harmonic generation microscopy, as
      well as cryo-EM, collectively demonstrated that the binding of nucleotide-free
      kinesin-1 to GDP microtubules changes the conformation of the GDP microtubule to
      a conformation resembling the GTP microtubule.

PMID- 30297394
TI  - Localized prosocial preferences, public goods, and common-pool resources.
AB  - The presence of prosocial preferences is thought to reduce significantly the
      difficulty of solving societal collective action problems such as providing
      public goods (or reducing public bads). However, prosociality is often limited to
      members of an in-group. We present a general theoretical model where society is
      split into subgroups and people care more about the welfare of others in their
      own subgroup than they do about those in out-groups. Individual contributions to
      the public good spill over and benefit members in each group to different
      degrees. We then consider special cases of our general model under which we can
      examine the consequences of localized prosociality for the economic outcomes of
      society as a whole. We ask to what extent prosociality closes the welfare gap
      between the Nash equilibrium without prosociality and the social optimum. The
      answer depends on whether private and public inputs are good or poor substitutes
      in producing final output. Critically, the degree to which this welfare gap
      closes is a concave function of the level of prosociality in the case of poor
      substitutes, so even low levels of prosociality can lead to social welfare near
      the social optimum.

PMID- 30297392
TI  - p38alpha MAPK signaling drives pharmacologically reversible brain and
      gastrointestinal phenotypes in the SERT Ala56 mouse.
AB  - Autism spectrum disorder (ASD) is a common neurobehavioral disorder with limited
      treatment options. Activation of p38 MAPK signaling networks has been identified
      in ASD, and p38 MAPK signaling elevates serotonin (5-HT) transporter (SERT)
      activity, effects mimicked by multiple, hyperfunctional SERT coding variants
      identified in ASD subjects. Mice expressing the most common of these variants
      (SERT Ala56) exhibit hyperserotonemia, a biomarker observed in ASD subjects, as
      well as p38 MAPK-dependent SERT hyperphosphorylation, elevated hippocampal 5-HT
      clearance, hypersensitivity of CNS 5-HT1A and 5-HT2A/2C receptors, and behavioral
      and gastrointestinal perturbations reminiscent of ASD. As the alpha-isoform of
      p38 MAPK drives SERT activation, we tested the hypothesis that CNS-penetrant,
      alpha-isoform-specific p38 MAPK inhibitors might normalize SERT Ala56 phenotypes.
      Strikingly, 1-week treatment of adult SERT Ala56 mice with MW150, a selective
      p38alpha MAPK inhibitor, normalized hippocampal 5-HT clearance, CNS 5-HT1A and 5
      HT2A/2C receptor sensitivities, social interactions, and colonic motility.
      Conditional elimination of p38alpha MAPK in 5-HT neurons of SERT Ala56 mice
      restored 5-HT1A and 5-HT2A/2C receptor sensitivities as well as social
      interactions, mirroring effects of MW150. Our findings support ongoing p38alpha
      MAPK activity as an important determinant of the physiological and behavioral
      perturbations of SERT Ala56 mice and, more broadly, supports consideration of
      p38alpha MAPK inhibition as a potential treatment for core and comorbid
      phenotypes present in ASD subjects.

PMID- 30297393
TI  - Histone methylation regulator PTIP is required to maintain normal and leukemic
      bone marrow niches.
AB  - The bone is essential for locomotion, calcium storage, and harboring the
      hematopoietic stem cells (HSCs) that supply the body with mature blood cells
      throughout life. HSCs reside at the interface of the bone and bone marrow (BM),
      where active bone remodeling takes place. Although the cellular components of the
      BM niche have been characterized, little is known about its epigenetic
      regulation. Here we find that the histone methylation regulator PTIP (Pax
      interaction with transcription-activation domain protein-1) is required to
      maintain the integrity of the BM niche by promoting osteoclast differentiation.
      PTIP directly promotes chromatin changes required for the expression of Ppargamma
      (peroxisome proliferator-activated receptor-gamma), a transcription factor
      essential for osteoclastogenesis. PTIP deletion leads to a drastic reduction of
      HSCs in the BM and induces extramedullary hematopoiesis. Furthermore, exposure of
      acute myeloid leukemia cells to a PTIP-deficient BM microenvironment leads to a
      reduction in leukemia-initiating cells and increased survival upon
      transplantation. Taken together, our data identify PTIP as an epigenetic
      regulator of osteoclastogenesis that is required for the integrity of the BM
      niche to sustain both normal hematopoiesis and leukemia.

PMID- 30297395
TI  - Protective immunity in recurrent Staphylococcus aureus infection reflects
      localized immune signatures and macrophage-conferred memory.
AB  - Staphylococcus aureus is the leading cause of skin and skin structure infection
      (SSSI), a primary portal of entry for invasive infection. Our prior studies
      discovered a role for protective innate memory against recurrent methicillin
      resistant S. aureus (MRSA) SSSI. In the present study, the dynamics and
      mechanisms of this response were explored in recurrent SSSI in WT mice. Priming
      by prior infection reduced skin lesion severity and MRSA burden, and protected
      against dissemination at day 7 but not day 2. Cytokine and cellular signatures in
      SSSI differed at day 2 versus 7, and were distinct in skin versus blood or
      spleen. Cytokines associated with protection in skin included increased IL-17, IL
      6, monokine inducible by IFN-gamma (MIG), and RANTES, while increased IP-10
      correlated with protection from dissemination. Cellular signatures of protection
      included increased Th17, M1 macrophage, and dendritic cell populations in
      abscesses, and total macrophages in lymph nodes. Priming potentiated S. aureus
      specific phagocytic killing by bone marrow-derived macrophages in vitro, and
      their adoptive transfer into naive skin afforded protective efficacy in vivo.
      Present findings indicate that protective immunity in recurrent S. aureus
      infection is locally targeted, and involves specific memory conferred by
      macrophages. These insights provide targets for vaccine and immunotherapeutic
      development against MRSA.

PMID- 30297396
TI  - iNOS promotes CD24+CD133+ liver cancer stem cell phenotype through a TACE/ADAM17
      dependent Notch signaling pathway.
AB  - The inducible nitric oxide synthase (iNOS) is associated with more aggressive
      solid tumors, including hepatocellular carcinoma (HCC). Notch signaling in cancer
      stem cells promotes cancer progression and requires Notch cleavage by ADAM (a
      disintegrin and metalloprotease) proteases. We hypothesized that iNOS/NO promotes
      Notch1 activation through TACE/ADAM17 activation in liver cancer stem cells
      (LCSCs), leading to a more aggressive cancer phenotype. Expression of the stem
      cell markers CD24 and CD133 in the tumors of patients with HCC was associated
      with greater iNOS expression and worse outcomes. The expression of iNOS in
      CD24+CD133+ LCSCs, but not CD24-CD133- LCSCs, promoted Notch1 signaling and
      stemness characteristics in vitro and in vivo, as well as accelerating HCC
      initiation and tumor formation in the mouse xenograft tumor model. iNOS/NO led to
      Notch1 signaling through a pathway involving the soluble guanylyl
      cyclase/cGMP/PKG-dependent activation of TACE/ADAM17 and up-regulation of iRhom2
      in LCSCs. In patients with HCC, higher TACE/ADAM17 expression and Notch1
      activation correlated with poor prognosis. These findings link iNOS to Notch1
      signaling in CD24+CD133+ LCSCs through the activation of TACE/ADAM17 and identify
      a mechanism for how iNOS contributes to progression of CD24+CD133+ HCC.

PMID- 30297398
TI  - Volatile loss following cooling and accretion of the Moon revealed by chromium
      isotopes.
AB  - Terrestrial and lunar rocks share chemical and isotopic similarities in
      refractory elements, suggestive of a common precursor. By contrast, the marked
      depletion of volatile elements in lunar rocks together with their enrichment in
      heavy isotopes compared with Earth's mantle suggests that the Moon underwent
      evaporative loss of volatiles. However, whether equilibrium prevailed during
      evaporation and, if so, at what conditions (temperature, pressure, and oxygen
      fugacity) remain unconstrained. Chromium may shed light on this question, as it
      has several thermodynamically stable, oxidized gas species that can distinguish
      between kinetic and equilibrium regimes. Here, we present high-precision Cr
      isotope measurements in terrestrial and lunar rocks that reveal an enrichment in
      the lighter isotopes of Cr in the Moon compared with Earth's mantle by 100 +/- 40
      ppm per atomic mass unit. This observation is consistent with Cr partitioning
      into an oxygen-rich vapor phase in equilibrium with the proto-Moon, thereby
      stabilizing the CrO2 species that is isotopically heavy compared with CrO in a
      lunar melt. Temperatures of 1,600-1,800 K and oxygen fugacities near the fayalite
      magnetite-quartz buffer are required to explain the elemental and isotopic
      difference of Cr between Earth's mantle and the Moon. These temperatures are far
      lower than modeled in the aftermath of a giant impact, implying that volatile
      loss did not occur contemporaneously with impact but following cooling and
      accretion of the Moon.

PMID- 30297397
TI  - Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC
      and the response to treatment with atezolizumab (anti-PD-L1).
AB  - Programmed death-ligand 1 (PD-L1) expression on tumor cells (TCs) by
      immunohistochemistry is rapidly gaining importance as a diagnostic for the
      selection or stratification of patients with non-small cell lung cancer (NSCLC)
      most likely to respond to single-agent checkpoint inhibitors. However, at least
      two distinct patterns of PD-L1 expression have been observed with potential
      biological and clinical relevance in NSCLC: expression on TC or on tumor
      infiltrating immune cells (ICs). We investigated the molecular and cellular
      characteristics associated with PD-L1 expression in these distinct cell
      compartments in 4,549 cases of NSCLC. PD-L1 expression on IC was more prevalent
      and likely reflected IFN-gamma-induced adaptive regulation accompanied by
      increased tumor-infiltrating lymphocytes and effector T cells. High PD-L1
      expression on TC, however, reflected an epigenetic dysregulation of the PD-L1
      gene and was associated with a distinct histology described by poor immune
      infiltration, sclerotic/desmoplastic stroma, and mesenchymal molecular features.
      Importantly, durable clinical responses to atezolizumab (anti-PD-L1) were
      observed in patients with tumors expressing high PD-L1 levels on either TC alone
      [40% objective response rate (ORR)] or IC alone (22% ORR). Thus, PD-L1 expression
      on TC or IC can independently attenuate anticancer immunity and emphasizes the
      functional importance of IC in regulating the antitumor T cell response.

PMID- 30297401
TI  - Correction for CaraDonna et al., Shifts in flowering phenology reshape a
      subalpine plant community.

PMID- 30297400
TI  - Neural reactivation in parietal cortex enhances memory for episodically linked
      information.
AB  - Remembering is a complex process that involves recalling specific details, such
      as who you were with when you celebrated your last birthday, as well as
      contextual information, such as the place where you celebrated. It is well
      established that the act of remembering enhances long-term retention of the
      retrieved information, but the neural and cognitive mechanisms that drive memory
      enhancement are not yet understood. One possibility is that the process of
      remembering results in reactivation of the broader episodic context. Consistent
      with this idea, in two experiments, we found that multiple retrieval attempts
      enhanced long-term retention of both the retrieved object and the nontarget
      object that shared scene context, compared with a restudy control. Using
      representational similarity analysis of fMRI data in experiment 2, we found that
      retrieval resulted in greater neural reactivation of both the target objects and
      contextually linked objects compared with restudy. Furthermore, this reactivation
      occurred in a network of medial and lateral parietal lobe regions that have been
      linked to episodic recollection. The results demonstrate that retrieving a memory
      can enhance retention of information that is linked in the broader event context
      and the hippocampus and a posterior medial network of parietal cortical areas
      (also known as the Default Network) play complementary roles in supporting the
      reactivation of episodically linked information during retrieval.

PMID- 30297399
TI  - Bottom trawl fishing footprints on the world's continental shelves.
AB  - Bottom trawlers land around 19 million tons of fish and invertebrates annually,
      almost one-quarter of wild marine landings. The extent of bottom trawling
      footprint (seabed area trawled at least once in a specified region and time
      period) is often contested but poorly described. We quantify footprints using
      high-resolution satellite vessel monitoring system (VMS) and logbook data on 24
      continental shelves and slopes to 1,000-m depth over at least 2 years. Trawling
      footprint varied markedly among regions: from <10% of seabed area in Australian
      and New Zealand waters, the Aleutian Islands, East Bering Sea, South Chile, and
      Gulf of Alaska to >50% in some European seas. Overall, 14% of the 7.8 million-km2
      study area was trawled, and 86% was not trawled. Trawling activity was
      aggregated; the most intensively trawled areas accounting for 90% of activity
      comprised 77% of footprint on average. Regional swept area ratio (SAR; ratio of
      total swept area trawled annually to total area of region, a metric of trawling
      intensity) and footprint area were related, providing an approach to estimate
      regional trawling footprints when high-resolution spatial data are unavailable.
      If SAR was <=0.1, as in 8 of 24 regions, there was >95% probability that >90% of
      seabed was not trawled. If SAR was 7.9, equal to the highest SAR recorded, there
      was >95% probability that >70% of seabed was trawled. Footprints were smaller and
      SAR was <=0.25 in regions where fishing rates consistently met international
      sustainability benchmarks for fish stocks, implying collateral environmental
      benefits from sustainable fishing.

PMID- 30297402
TI  - Functional and evolutionary characterization of a secondary metabolite gene
      cluster in budding yeasts.
AB  - Secondary metabolites are key in how organisms from all domains of life interact
      with their environment and each other. The iron-binding molecule pulcherrimin was
      described a century ago, but the genes responsible for its production in budding
      yeasts have remained uncharacterized. Here, we used phylogenomic footprinting on
      90 genomes across the budding yeast subphylum Saccharomycotina to identify the
      gene cluster associated with pulcherrimin production. Using targeted gene
      replacements in Kluyveromyces lactis, we characterized the four genes that make
      up the cluster, which likely encode two pulcherriminic acid biosynthesis enzymes,
      a pulcherrimin transporter, and a transcription factor involved in both
      biosynthesis and transport. The requirement of a functional putative transporter
      to utilize extracellular pulcherrimin-complexed iron demonstrates that
      pulcherriminic acid is a siderophore, a chelator that binds iron outside the cell
      for subsequent uptake. Surprisingly, we identified homologs of the putative
      transporter and transcription factor genes in multiple yeast genera that lacked
      the biosynthesis genes and could not make pulcherrimin, including the model yeast
      Saccharomyces cerevisiae We deleted these previously uncharacterized genes and
      showed they are also required for pulcherrimin utilization in S. cerevisiae,
      raising the possibility that other genes of unknown function are linked to
      secondary metabolism. Phylogenetic analyses of this gene cluster suggest that
      pulcherrimin biosynthesis and utilization were ancestral to budding yeasts, but
      the biosynthesis genes and, subsequently, the utilization genes, were lost in
      many lineages, mirroring other microbial public goods systems that lead to the
      rise of cheater organisms.

PMID- 30297403
TI  - Changes in temperature alter the relationship between biodiversity and ecosystem
      functioning.
AB  - Global warming and the loss of biodiversity through human activities (e.g., land
      use change, pollution, invasive species) are two of the most profound threats to
      the functional integrity of the Earth's ecosystems. These factors are, however,
      most frequently investigated separately, ignoring the potential for synergistic
      effects of biodiversity loss and environmental warming on ecosystem functioning.
      Here we use high-throughput experiments with microbial communities to investigate
      how changes in temperature affect the relationship between biodiversity and
      ecosystem functioning. We found that changes in temperature systematically
      altered the relationship between biodiversity and ecosystem functioning. As
      temperatures departed from ambient conditions the exponent of the diversity
      functioning relationship increased, meaning that more species were required to
      maintain ecosystem functioning under thermal stress. This key result was driven
      by two processes linked to variability in the thermal tolerance curves of taxa.
      First, more diverse communities had a greater chance of including species with
      thermal traits that enabled them to maintain productivity as temperatures shifted
      from ambient conditions. Second, we found a pronounced increase in the
      contribution of complementarity to the net biodiversity effect at high and low
      temperatures, indicating that changes in species interactions played a critical
      role in mediating the impacts of temperature change on the relationship between
      biodiversity and ecosystem functioning. Our results highlight that if
      biodiversity loss occurs independently of species' thermal tolerance traits, then
      the additional impacts of environmental warming will result in sharp declines in
      ecosystem function.

PMID- 30297405
TI  - Correction for Sanchez et al., Near-term deployment of carbon capture and
      sequestration from biorefineries in the United States.

PMID- 30297404
TI  - Mitosis-specific MRN complex promotes a mitotic signaling cascade to regulate
      spindle dynamics and chromosome segregation.
AB  - The MRE11-RAD50-NBS1 (MRN) complex is well known for participating in DNA damage
      response pathways in all phases of cell cycle. Here, we show that MRN constitutes
      a mitosis-specific complex, named mMRN, with a protein, MMAP. MMAP directly
      interacts with MRE11 and is required for optimal stability of the MRN complex
      during mitosis. MMAP colocalizes with MRN in mitotic spindles, and MMAP-deficient
      cells display abnormal spindle dynamics and chromosome segregation similar to MRN
      deficient cells. Mechanistically, both MMAP and MRE11 are hyperphosphorylated by
      the mitotic kinase, PLK1; and the phosphorylation is required for assembly of the
      mMRN complex. The assembled mMRN complex enables PLK1 to interact with and
      activate the microtubule depolymerase, KIF2A, leading to spindle turnover and
      chromosome segregation. Our study identifies a mitosis-specific version of the
      MRN complex that acts in the PLK1-KIF2A signaling cascade to regulate spindle
      dynamics and chromosome distribution.

PMID- 30297406
TI  - Selection and gene flow shape genomic islands that control floral guides.
AB  - Genomes of closely-related species or populations often display localized regions
      of enhanced relative sequence divergence, termed genomic islands. It has been
      proposed that these islands arise through selective sweeps and/or barriers to
      gene flow. Here, we genetically dissect a genomic island that controls flower
      color pattern differences between two subspecies of Antirrhinum majus,
      A.m.striatum and A.m.pseudomajus, and relate it to clinal variation across a
      natural hybrid zone. We show that selective sweeps likely raised relative
      divergence at two tightly-linked MYB-like transcription factors, leading to
      distinct flower patterns in the two subspecies. The two patterns provide
      alternate floral guides and create a strong barrier to gene flow where
      populations come into contact. This barrier affects the selected flower color
      genes and tightly-linked loci, but does not extend outside of this domain,
      allowing gene flow to lower relative divergence for the rest of the chromosome.
      Thus, both selective sweeps and barriers to gene flow play a role in shaping
      genomic islands: sweeps cause elevation in relative divergence, while
      heterogeneous gene flow flattens the surrounding "sea," making the island of
      divergence stand out. By showing how selective sweeps establish alternative
      adaptive phenotypes that lead to barriers to gene flow, our study sheds light on
      possible mechanisms leading to reproductive isolation and speciation.

PMID- 30297407
TI  - Magnetic map in nonanadromous Atlantic salmon.
AB  - Long-distance migrants, including Pacific salmon (Oncorhynchus spp), can use
      geomagnetic information to navigate. We tested the hypothesis that a "magnetic
      map" (i.e., an ability to extract positional information from Earth's magnetic
      field) also exists in a population of salmon that do not undertake oceanic
      migrations. This study examined juvenile Atlantic salmon (Salmo salar) originally
      from a nonanadromous population in Maine transferred ~60 years ago to a lake in
      central Oregon. We exposed juveniles to magnetic displacements representative of
      locations at the latitudinal boundaries of the Pacific salmon oceanic range in
      the North Pacific and at the periphery of their ancestral oceanic range in the
      North Atlantic. Orientation differed among the magnetic treatments, indicating
      that Atlantic salmon detect map information from the geomagnetic field. Despite
      no recent history of ocean migration, these fish displayed adaptive orientation
      responses similar to those observed in native Pacific salmonids. These findings
      indicate that use of map information from the geomagnetic field is a shared
      ancestral character in the family Salmonidae and is not restricted to populations
      with anadromous life histories. Lastly, given that Atlantic salmon are
      transported throughout the world for capture fisheries and aquaculture, such a
      robust navigational system is of some concern. Escaped individuals may have
      greater potential to successfully navigate, and thus invade, introduced habitats
      than previously suspected.

PMID- 30297408
TI  - Interplay between coronavirus, a cytoplasmic RNA virus, and nonsense-mediated
      mRNA decay pathway.
AB  - Coronaviruses (CoVs), including severe acute respiratory syndrome CoV and Middle
      East respiratory syndrome CoV, are enveloped RNA viruses that carry a large
      positive-sense single-stranded RNA genome and cause a variety of diseases in
      humans and domestic animals. Very little is known about the host pathways that
      regulate the stability of CoV mRNAs, which carry some unusual features. Nonsense
      mediated decay (NMD) is a eukaryotic RNA surveillance pathway that detects mRNAs
      harboring aberrant features and targets them for degradation. Although CoV mRNAs
      are of cytoplasmic origin, the presence of several NMD-inducing features
      (including multiple ORFs with internal termination codons that create a long 3'
      untranslated region) in CoV mRNAs led us to explore the interplay between the NMD
      pathway and CoVs. Our study using murine hepatitis virus as a model CoV showed
      that CoV mRNAs are recognized by the NMD pathway as a substrate, resulting in
      their degradation. Furthermore, CoV replication induced the inhibition of the NMD
      pathway, and N protein (a viral structural protein) had an NMD inhibitory
      function that protected viral mRNAs from rapid decay. Our data further suggest
      that the NMD pathway interferes with optimal viral replication by degrading viral
      mRNAs early in infection, before sufficient accumulation of N protein. Our study
      presents clear evidence for the biological importance of the NMD pathway in
      controlling the stability of mRNAs and the efficiency of replication of a
      cytoplasmic RNA virus.

PMID- 30297410
TI  - Correction for Lee et al., Altered ER-mitochondria contact impacts mitochondria
      calcium homeostasis and contributes to neurodegeneration in vivo in disease
      models.

PMID- 30297409
TI  - Yin-and-yang bifurcation of opioidergic circuits for descending analgesia at the
      midbrain of the mouse.
AB  - In the descending analgesia pathway, opioids are known to disinhibit the
      projections from the periaqueductal gray (PAG) to the rostral ventromedial
      medulla (RVM), leading to suppression of pain signals at the spinal cord level.
      The locus coeruleus (LC) has been proposed to engage in the descending pathway
      through noradrenergic inputs to the spinal cord. Nevertheless, how the LC is
      integrated in the descending analgesia circuit has remained unknown. Here, we
      show that the opioidergic analgesia pathway is bifurcated in structure and
      function at the PAG. A knockout as well as a PAG-specific knockdown of
      phospholipase C beta4 (PLCbeta4), a signaling molecule for G protein-coupled
      receptors, enhanced swim stress-induced and morphine-induced analgesia in mice.
      Immunostaining after simultaneous retrograde labeling from the RVM and the LC
      revealed two mutually exclusive neuronal populations at the PAG, each projecting
      either to the LC or the RVM, with PLCbeta4 expression only in the PAG-LC
      projecting cells that provide a direct synaptic input to LC-spinal cord (SC)
      projection neurons. The PAG-LC projection neurons in wild-type mice turned
      quiescent in response to opiates, but remained active in the PLCbeta4 mutant,
      suggesting a possibility that an increased adrenergic function induced by the
      persistent PAG-LC activity underlies the enhanced opioid analgesia in the mutant.
      Indeed, the enhanced analgesia in the mutant was reversed by blocking alpha2
      noradrenergic receptors. These findings indicate that opioids suppress descending
      analgesia through the PAG-LC pathway, while enhancing it through the PAG-RVM
      pathway, i.e., two distinct pathways with opposing effects on opioid analgesia.
      These results point to a therapeutic target in pain control.

PMID- 30297412
TI  - Progressive aridification in East Africa over the last half million years and
      implications for human evolution.
AB  - Evidence for Quaternary climate change in East Africa has been derived from
      outcrops on land and lake cores and from marine dust, leaf wax, and pollen
      records. These data have previously been used to evaluate the impact of climate
      change on hominin evolution, but correlations have proved to be difficult, given
      poor data continuity and the great distances between marine cores and terrestrial
      basins where fossil evidence is located. Here, we present continental coring
      evidence for progressive aridification since about 575 thousand years before
      present (ka), based on Lake Magadi (Kenya) sediments. This long-term drying trend
      was interrupted by many wet-dry cycles, with the greatest variability developing
      during times of high eccentricity-modulated precession. Intense aridification
      apparent in the Magadi record took place between 525 and 400 ka, with relatively
      persistent arid conditions after 350 ka and through to the present. Arid
      conditions in the Magadi Basin coincide with the Mid-Brunhes Event and overlap
      with mammalian extinctions in the South Kenya Rift between 500 and 400 ka. The
      525 to 400 ka arid phase developed in the South Kenya Rift between the period
      when the last Acheulean tools are reported (at about 500 ka) and before the
      appearance of Middle Stone Age artifacts (by about 320 ka). Our data suggest that
      increasing Middle- to Late-Pleistocene aridification and environmental
      variability may have been drivers in the physical and cultural evolution of Homo
      sapiens in East Africa.

PMID- 30297411
TI  - Dopaminergic basis for signaling belief updates, but not surprise, and the link
      to paranoia.
AB  - Distinguishing between meaningful and meaningless sensory information is
      fundamental to forming accurate representations of the world. Dopamine is thought
      to play a central role in processing the meaningful information content of
      observations, which motivates an agent to update their beliefs about the
      environment. However, direct evidence for dopamine's role in human belief
      updating is lacking. We addressed this question in healthy volunteers who
      performed a model-based fMRI task designed to separate the neural processing of
      meaningful and meaningless sensory information. We modeled participant behavior
      using a normative Bayesian observer model and used the magnitude of the model
      derived belief update following an observation to quantify its meaningful
      information content. We also acquired PET imaging measures of dopamine function
      in the same subjects. We show that the magnitude of belief updates about task
      structure (meaningful information), but not pure sensory surprise (meaningless
      information), are encoded in midbrain and ventral striatum activity. Using PET we
      show that the neural encoding of meaningful information is negatively related to
      dopamine-2/3 receptor availability in the midbrain and dexamphetamine-induced
      dopamine release capacity in the striatum. Trial-by-trial analysis of task
      performance indicated that subclinical paranoid ideation is negatively related to
      behavioral sensitivity to observations carrying meaningful information about the
      task structure. The findings provide direct evidence implicating dopamine in
      model-based belief updating in humans and have implications for understating the
      pathophysiology of psychotic disorders where dopamine function is disrupted.

PMID- 30297413
TI  - Entropic contribution to enhanced thermal stability in the thermostable P450
      CYP119.
AB  - The enhanced thermostability of thermophilic proteins with respect to their
      mesophilic counterparts is often attributed to the enthalpy effect, arising from
      strong interactions between protein residues. Intuitively, these strong
      interresidue interactions will rigidify the biomolecules. However, the present
      work utilizing neutron scattering and solution NMR spectroscopy measurements
      demonstrates a contrary example that the thermophilic cytochrome P450, CYP119, is
      much more flexible than its mesophilic counterpart, CYP101A1, something which is
      not apparent just from structural comparison of the two proteins. A mechanism to
      explain this apparent contradiction is that higher flexibility in the folded
      state of CYP119 increases its conformational entropy and thereby reduces the
      entropy gain during denaturation, which will increase the free energy needed for
      unfolding and thus stabilize the protein. This scenario is supported by
      thermodynamic data on the temperature dependence of unfolding free energy, which
      shows a significant entropic contribution to the thermostability of CYP119 and
      lends an added dimension to enhanced stability, previously attributed only to
      presence of aromatic stacking interactions and salt bridge networks. Our
      experimental data also support the notion that highly thermophilic P450s such as
      CYP119 may use a mechanism that partitions flexibility differently from
      mesophilic P450s between ligand binding and thermal stability.

PMID- 30297414
TI  - MRI-based assessment of function and dysfunction in myelinated axons.
AB  - Repetitive electrical activity produces microstructural alteration in myelinated
      axons, which may afford the opportunity to noninvasively monitor function of
      myelinated fibers in peripheral nervous system (PNS)/CNS pathways.
      Microstructural changes were assessed via two different magnetic-resonance-based
      approaches: diffusion fMRI and dynamic T2 spectroscopy in the ex vivo perfused
      bullfrog sciatic nerves. Using this robust, classical model as a platform for
      testing, we demonstrate that noninvasive diffusion fMRI, based on standard
      diffusion tensor imaging (DTI), can clearly localize the sites of axonal
      conduction blockage as might be encountered in neurotrauma or other lesion types.
      It is also shown that the diffusion fMRI response is graded in proportion to the
      total number of electrical impulses carried through a given locus. Dynamic T2
      spectroscopy of the perfused frog nerves point to an electrical-activity-induced
      redistribution of tissue water and myelin structural changes. Diffusion basis
      spectrum imaging (DBSI) reveals a reversible shift of tissue water into a
      restricted isotropic diffusion signal component. Submyelinic vacuoles are
      observed in electron-microscopy images of tissue fixed during electrical
      stimulation. A slowing of the compound action potential conduction velocity
      accompanies repetitive electrical activity. Correlations between
      electrophysiology and MRI parameters during and immediately after stimulation are
      presented. Potential mechanisms and interpretations of these results are
      discussed.

PMID- 30297416
TI  - Salt and marine products in the Classic Maya economy from use-wear study of stone
      tools.
AB  - Microscopic study of the edges of Late to Terminal Classic Maya (AD 600-900)
      chert stone tools from the Paynes Creek Salt Works, Belize, indicates most tools
      were used for cutting fish or meat or working hide, which was unexpected, given
      the virtual absence of fish or other animal remains at this large salt-production
      complex. Use-wear study shows that a minority of stone tools have edge-wear from
      woodworking. Our study suggests that salting fish was a significant activity at
      the salt works, which corresponds to Roman, Chinese, and other East Asian
      civilizations, where salt and salted fish were critical components of food
      storage, trade, and state finance. Based on analogy with modern Maya salt
      producers at Sacapulas, Guatemala, we provide estimates of the amounts of salt
      and salted fish produced at the Paynes Creek Salt Works and the implications for
      the Classic Maya economy. Salt cakes and salted fish were preserved commodities
      that could be stored and traded in the marketplace.

PMID- 30297415
TI  - Long noncoding RNA GM12371 acts as a transcriptional regulator of synapse
      function.
AB  - Despite the growing evidence suggesting that long noncoding RNAs (lncRNAs) are
      critical regulators of several biological processes, their functions in the
      nervous system remain elusive. We have identified an lncRNA, GM12371, in
      hippocampal neurons that is enriched in the nucleus and necessary for synaptic
      communication, synapse density, synapse morphology, and dendritic tree
      complexity. Mechanistically, GM12371 regulates the expression of several genes
      involved in neuronal development and differentiation, as well as expression of
      specific lncRNAs and their cognate mRNA targets. Furthermore, we find that cAMP
      PKA signaling up-regulates the expression of GM12371 and that its expression is
      essential for the activity-dependent changes in synaptic transmission in
      hippocampal neurons. Taken together, our data establish a key role for GM12371 in
      regulating synapse function.

PMID- 30297417
TI  - Elongation factor P is required to maintain proteome homeostasis at high growth
      rate.
AB  - Elongation factor P (EF-P) is a universally conserved translation factor that
      alleviates ribosome pausing at polyproline (PPX) motifs by facilitating peptide
      bond formation. In the absence of EF-P, PPX peptide bond formation can limit
      translation rate, leading to pleotropic phenotypes including slowed growth,
      increased antibiotic sensitivity, and loss of virulence. In this study, we
      observe that many of these phenotypes are dependent on growth rate. Limiting
      growth rate suppresses a variety of detrimental phenotypes associated with
      ribosome pausing at PPX motifs in the absence of EF-P. Polysome levels are also
      similar to wild-type under slow growth conditions, consistent with global changes
      in ribosome queuing in cells without EF-P when growth rate is decreased.
      Inversely, under high protein synthesis demands, we observe that Escherichia coli
      lacking EF-P have reduced fitness. Our data demonstrate that EF-P-mediated relief
      of ribosome queuing is required to maintain proteome homeostasis under conditions
      of high translational demands.

PMID- 30297418
TI  - DSCAM promotes self-avoidance in the developing mouse retina by masking the
      functions of cadherin superfamily members.
AB  - During neural development, self-avoidance ensures that a neuron's processes
      arborize to evenly fill a particular spatial domain. At the individual cell
      level, self-avoidance is promoted by genes encoding cell-surface molecules
      capable of generating thousands of diverse isoforms, such as Dscam1 (Down
      syndrome cell adhesion molecule 1) in Drosophila Isoform choice differs between
      neighboring cells, allowing neurons to distinguish "self" from "nonself". In the
      mouse retina, Dscam promotes self-avoidance at the level of cell types, but
      without extreme isoform diversity. Therefore, we hypothesize that DSCAM is a
      general self-avoidance cue that "masks" other cell type-specific adhesion systems
      to prevent overly exuberant adhesion. Here, we provide in vivo and in vitro
      evidence that DSCAM masks the functions of members of the cadherin superfamily,
      supporting this hypothesis. Thus, unlike the isoform-rich molecules tasked with
      self-avoidance at the individual cell level, here the diversity resides on the
      adhesive side, positioning DSCAM as a generalized modulator of cell adhesion
      during neural development.

PMID- 30297420
TI  - Distinct facial expressions represent pain and pleasure across cultures.
AB  - Real-world studies show that the facial expressions produced during pain and
      orgasm-two different and intense affective experiences-are virtually
      indistinguishable. However, this finding is counterintuitive, because facial
      expressions are widely considered to be a powerful tool for social interaction.
      Consequently, debate continues as to whether the facial expressions of these
      extreme positive and negative affective states serve a communicative function.
      Here, we address this debate from a novel angle by modeling the mental
      representations of dynamic facial expressions of pain and orgasm in 40 observers
      in each of two cultures (Western, East Asian) using a data-driven method. Using a
      complementary approach of machine learning, an information-theoretic analysis,
      and a human perceptual discrimination task, we show that mental representations
      of pain and orgasm are physically and perceptually distinct in each culture.
      Cross-cultural comparisons also revealed that pain is represented by similar face
      movements across cultures, whereas orgasm showed distinct cultural accents.
      Together, our data show that mental representations of the facial expressions of
      pain and orgasm are distinct, which questions their nondiagnosticity and instead
      suggests they could be used for communicative purposes. Our results also
      highlight the potential role of cultural and perceptual factors in shaping the
      mental representation of these facial expressions. We discuss new research
      directions to further explore their relationship to the production of facial
      expressions.

PMID- 30297421
TI  - Faults and associated karst collapse suggest conduits for fluid flow that
      influence hydraulic fracturing-induced seismicity.
AB  - During December 2011, a swarm of moderate-magnitude earthquakes was induced by
      hydraulic fracturing (HF) near Cardston, Alberta. Despite seismological
      associations linking these two processes, the hydrological and tectonic
      mechanisms involved remain unclear. In this study, we interpret a 3D reflection
      seismic survey to delve into the geological factors related to these earthquakes.
      First, we document a basement-rooted fault on which the earthquake rupture
      occurred that extends above the targeted reservoir. Second, at the reservoir's
      stratigraphic level, anomalous subcircular features are recognized along the
      fault and are interpreted as resulting from fault-associated karst processes.
      These observations have implications for HF-induced seismicity, as they suggest
      hydraulic communication over a large (vertical) distance, reconciling the
      discrepancy between the culprit well trajectory and earthquake hypocenters. We
      speculate on how these newly identified geological factors could drive the
      sporadic appearance of induced seismicity and thus be utilized to avoid
      earthquake hazards.

PMID- 30297422
TI  - Randomly distributed embedding making short-term high-dimensional data
      predictable.
AB  - Future state prediction for nonlinear dynamical systems is a challenging task,
      particularly when only a few time series samples for high-dimensional variables
      are available from real-world systems. In this work, we propose a model-free
      framework, named randomly distributed embedding (RDE), to achieve accurate future
      state prediction based on short-term high-dimensional data. Specifically, from
      the observed data of high-dimensional variables, the RDE framework randomly
      generates a sufficient number of low-dimensional "nondelay embeddings" and maps
      each of them to a "delay embedding," which is constructed from the data of a to
      be predicted target variable. Any of these mappings can perform as a low
      dimensional weak predictor for future state prediction, and all of such mappings
      generate a distribution of predicted future states. This distribution actually
      patches all pieces of association information from various embeddings unbiasedly
      or biasedly into the whole dynamics of the target variable, which after operated
      by appropriate estimation strategies, creates a stronger predictor for achieving
      prediction in a more reliable and robust form. Through applying the RDE framework
      to data from both representative models and real-world systems, we reveal that a
      high-dimension feature is no longer an obstacle but a source of information
      crucial to accurate prediction for short-term data, even under noise
      deterioration.

PMID- 30297423
TI  - Mountain snowpack response to different levels of warming.
AB  - Temperature variability impacts the distribution and persistence of the mountain
      snowpack, which critically provides snowmelt-derived water resources to large
      populations worldwide. Warmer temperatures decrease the amount of montane snow
      water equivalent (SWE), forcing its center of mass to higher elevations. We use a
      unique multivariate probabilistic framework to quantify the response of the 1
      April SWE volume and its centroid to a 1.0 to 2.0  degrees C increase in winter
      air temperature across the Sierra Nevada (United States). A 1.0  degrees C
      increase reduces the probability of exceeding the long-term (1985-2016) average
      rangewide SWE volume (15.7 km3) by 20.7%. It correspondingly is 60.6% more likely
      for the centroid to be higher than its long-term average (2,540 m). We further
      show that a 1.5 and 2.0  degrees C increase in the winter temperature reduces the
      probability of exceeding the long-term average SWE volume by 31.0% and 41.1%,
      respectively, whereas it becomes 79.3% and 89.8% more likely that the centroid
      will be higher than 2,540 m for those respective temperature changes. We also
      characterize regional variability across the Sierra Nevada and show that the
      northwestern and southeastern regions of the mountain range are 30.3% and 14.0%
      less likely to have 1 April SWE volumes exceed their long-term average for a 1.0 
      degrees C increase about their respective average winter temperatures. Overall,
      the SWE in the northern Sierra Nevada exhibits higher hydrologic vulnerability to
      warming than in the southern region. Given the expected increases in mountain
      temperatures, the observed rates of change in SWE are expected to intensify in
      the future.

PMID- 30297419
TI  - Swi5-Sfr1 stimulates Rad51 recombinase filament assembly by modulating Rad51
      dissociation.
AB  - Eukaryotic Rad51 protein is essential for homologous-recombination repair of DNA
      double-strand breaks. Rad51 recombinases first assemble onto single-stranded DNA
      to form a nucleoprotein filament, required for function in homology pairing and
      strand exchange. This filament assembly is the first regulation step in
      homologous recombination. Rad51 nucleation is kinetically slow, and several
      accessory factors have been identified to regulate this step. Swi5-Sfr1 (S5S1)
      stimulates Rad51-mediated homologous recombination by stabilizing Rad51
      nucleoprotein filaments, but the mechanism of stabilization is unclear. We used
      single-molecule tethered particle motion experiments to show that mouse S5S1
      (mS5S1) efficiently stimulates mouse RAD51 (mRAD51) nucleus formation and
      inhibits mRAD51 dissociation from filaments. We also used single-molecule
      fluorescence resonance energy transfer experiments to show that mS5S1 promotes
      stable nucleus formation by specifically preventing mRAD51 dissociation. This
      leads to a reduction of nucleation size from three mRAD51 to two mRAD51 molecules
      in the presence of mS5S1. Compared with mRAD51, fission yeast Rad51 (SpRad51)
      exhibits fast nucleation but quickly dissociates from the filament. SpS5S1
      specifically reduces SpRad51 disassembly to maintain a stable filament. These
      results clearly demonstrate the conserved function of S5S1 by primarily
      stabilizing Rad51 on DNA, allowing both the formation of the stable nucleus and
      the maintenance of filament length.

PMID- 30297424
TI  - Empirical evidence of mental health risks posed by climate change.
AB  - Sound mental health-a critical facet of human wellbeing-has the potential to be
      undermined by climate change. Few large-scale studies have empirically examined
      this hypothesis. Here, we show that short-term exposure to more extreme weather,
      multiyear warming, and tropical cyclone exposure each associate with worsened
      mental health. To do so, we couple meteorological and climatic data with reported
      mental health difficulties drawn from nearly 2 million randomly sampled US
      residents between 2002 and 2012. We find that shifting from monthly temperatures
      between 25  degrees C and 30  degrees C to >30  degrees C increases the
      probability of mental health difficulties by 0.5% points, that 1 degrees C of 5
      year warming associates with a 2% point increase in the prevalence of mental
      health issues, and that exposure to Hurricane Katrina associates with a 4% point
      increase in this metric. Our analyses provide added quantitative support for the
      conclusion that environmental stressors produced by climate change pose threats
      to human mental health.

PMID- 30297425
TI  - Whole-genome comparison of endogenous retrovirus segregation across wild and
      domestic host species populations.
AB  - Although recent advances in sequencing and computational analyses have
      facilitated use of endogenous retroviruses (ERVs) for deciphering coevolution
      among retroviruses and their hosts, sampling effects from different host
      populations present major challenges. Here we utilize available whole-genome data
      from wild and domesticated European rabbit (Oryctolagus cuniculus sp.)
      populations, sequenced as DNA pools by paired-end Illumina technology, for
      identifying segregating reference as well as nonreference ERV loci, to reveal
      their variation along the host phylogeny and domestication history. To produce
      new viruses, retroviruses must insert a proviral DNA copy into the host nuclear
      DNA. Occasional proviral insertions into the host germline have been passed down
      through generations as inherited ERVs during millions of years. These ERVs
      represent retroviruses that were active at the time of infection and thus present
      a remarkable record of historical virus-host associations. To examine segregating
      ERVs in host populations, we apply a reference library search strategy for
      anchoring ERV-associated short-sequence read pairs from pooled whole-genome
      sequences to reference genome assembly positions. We show that most ERVs
      segregate along host phylogeny but also uncover radiation of some ERVs,
      identified as segregating loci among wild and domestic rabbits. The study targets
      pertinent issues regarding genome sampling when examining virus-host evolution
      from the genomic ERV record and offers improved scope regarding common strategies
      for single-nucleotide variant analyses in host population comparative genomics.

PMID- 30297427
TI  - Profile of Mary E. Hatten.

PMID- 30297426
TI  - mTORC1 signaling suppresses Wnt/beta-catenin signaling through DVL-dependent
      regulation of Wnt receptor FZD level.
AB  - Wnt/beta-catenin signaling plays pivotal roles in cell proliferation and tissue
      homeostasis by maintaining somatic stem cell functions. The mammalian target of
      rapamycin (mTOR) signaling functions as an integrative rheostat that orchestrates
      various cellular and metabolic activities that shape tissue homeostasis. Whether
      these two fundamental signaling pathways couple to exert physiological functions
      still remains mysterious. Using a genome-wide CRISPR-Cas9 screening, we discover
      that mTOR complex 1 (mTORC1) signaling suppresses canonical Wnt/beta-catenin
      signaling. Deficiency in tuberous sclerosis complex 1/2 (TSC1/2), core negative
      regulators of mTORC1 activity, represses Wnt/beta-catenin target gene expression,
      which can be rescued by RAD001. Mechanistically, mTORC1 signaling regulates the
      cell surface level of Wnt receptor Frizzled (FZD) in a Dishevelled (DVL)
      dependent manner by influencing the association of DVL and clathrin AP-2 adaptor.
      Sustained mTORC1 activation impairs Wnt/beta-catenin signaling and causes loss of
      stemness in intestinal organoids ex vivo and primitive intestinal progenitors in
      vivo. Wnt/beta-catenin-dependent liver metabolic zonation gene expression program
      is also down-regulated by mTORC1 activation. Our study provides a paradigm that
      mTORC1 signaling cell autonomously regulates Wnt/beta-catenin pathway to
      influence stem cell maintenance.

PMID- 30297429
TI  - Cryo-ET reveals the macromolecular reorganization of S. pombe mitotic chromosomes
      in vivo.
AB  - Chromosomes condense during mitosis in most eukaryotes. This transformation
      involves rearrangements at the nucleosome level and has consequences for
      transcription. Here, we use cryo-electron tomography (cryo-ET) to determine the
      3D arrangement of nuclear macromolecular complexes, including nucleosomes, in
      frozen-hydrated Schizosaccharomyces pombe cells. Using 3D classification
      analysis, we did not find evidence that nucleosomes resembling the crystal
      structure are abundant. This observation and those from other groups support the
      notion that a subset of fission yeast nucleosomes may be partially unwrapped in
      vivo. In both interphase and mitotic cells, there is also no evidence of
      monolithic structures the size of Hi-C domains. The chromatin is mingled with two
      features: pockets, which are positions free of macromolecular complexes; and
      "megacomplexes," which are multimegadalton globular complexes like preribosomes.
      Mitotic chromatin is more crowded than interphase chromatin in subtle ways.
      Nearest-neighbor distance analyses show that mitotic chromatin is more compacted
      at the oligonucleosome than the dinucleosome level. Like interphase, mitotic
      chromosomes contain megacomplexes and pockets. This uneven chromosome
      condensation helps explain a longstanding enigma of mitosis: a subset of genes is
      up-regulated.

PMID- 30297428
TI  - Genetic variation in the SIM1 locus is associated with erectile dysfunction.
AB  - Erectile dysfunction affects millions of men worldwide. Twin studies support the
      role of genetic risk factors underlying erectile dysfunction, but no specific
      genetic variants have been identified. We conducted a large-scale genome-wide
      association study of erectile dysfunction in 36,649 men in the multiethnic Kaiser
      Permanente Northern California Genetic Epidemiology Research in Adult Health and
      Aging cohort. We also undertook replication analyses in 222,358 men from the UK
      Biobank. In the discovery cohort, we identified a single locus (rs17185536-T) on
      chromosome 6 near the single-minded family basic helix-loop-helix transcription
      factor 1 (SIM1) gene that was significantly associated with the risk of erectile
      dysfunction (odds ratio = 1.26, P = 3.4 * 10-25). The association replicated in
      the UK Biobank sample (odds ratio = 1.25, P = 6.8 * 10-14), and the effect is
      independent of known erectile dysfunction risk factors, including body mass index
      (BMI). The risk locus resides on the same topologically associating domain as
      SIM1 and interacts with the SIM1 promoter, and the rs17185536-T risk allele
      showed differential enhancer activity. SIM1 is part of the leptin-melanocortin
      system, which has an established role in body weight homeostasis and sexual
      function. Because the variants associated with erectile dysfunction are not
      associated with differences in BMI, our findings suggest a mechanism that is
      specific to sexual function.

PMID- 30297431
TI  - Topological quantum computation based on chiral Majorana fermions.
AB  - The chiral Majorana fermion is a massless self-conjugate fermion which can arise
      as the edge state of certain 2D topological matters. It has been theoretically
      predicted and experimentally observed in a hybrid device of a quantum anomalous
      Hall insulator and a conventional superconductor. Its closely related cousin, the
      Majorana zero mode in the bulk of the corresponding topological matter, is known
      to be applicable in topological quantum computations. Here we show that the
      propagation of chiral Majorana fermions leads to the same unitary transformation
      as that in the braiding of Majorana zero modes and propose a platform to perform
      quantum computation with chiral Majorana fermions. A Corbino ring junction of the
      hybrid device can use quantum coherent chiral Majorana fermions to implement the
      Hadamard gate and the phase gate, and the junction conductance yields a natural
      readout for the qubit state.

PMID- 30297430
TI  - Humans incorporate attention-dependent uncertainty into perceptual decisions and
      confidence.
AB  - Perceptual decisions are better when they take uncertainty into account.
      Uncertainty arises not only from the properties of sensory input but also from
      cognitive sources, such as different levels of attention. However, it is unknown
      whether humans appropriately adjust for such cognitive sources of uncertainty
      during perceptual decision-making. Here we show that, in a task in which
      uncertainty is relevant for performance, human categorization and confidence
      decisions take into account uncertainty related to attention. We manipulated
      uncertainty in an orientation categorization task from trial to trial using only
      an attentional cue. The categorization task was designed to disambiguate decision
      rules that did or did not depend on attention. Using formal model comparison to
      evaluate decision behavior, we found that category and confidence decision
      boundaries shifted as a function of attention in an approximately Bayesian
      fashion. This means that the observer's attentional state on each trial
      contributed probabilistically to the decision computation. This responsiveness of
      an observer's decisions to attention-dependent uncertainty should improve
      perceptual decisions in natural vision, in which attention is unevenly
      distributed across a scene.

PMID- 30297432
TI  - Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral
      injection and results in durable antitumor immunity.
AB  - Immune stimulation has emerged as a promising approach to the treatment of
      neoplastic diseases. Currently approved therapeutics, such as anti-CTLA4 and anti
      PD1, are primarily aimed at blocking inhibitory signaling by immune cells. An
      alternative and potentially synergistic approach would involve activation of
      immune pathways by agonism of stimulatory receptors, such as CD40. Agonistic
      antibodies, while promising in principle, have encountered significant barriers
      in clinical trials limited by the systemic toxicity of such approaches. Using a
      mouse model humanized for both Fc receptors and CD40, we previously demonstrated
      enhanced antitumor activity with an Fc-modified antibody. We now demonstrate that
      this model recapitulates the platelet and hepatic toxicities seen with anti-CD40
      antibodies in patients, providing a predictive measure of the dose-limiting
      activity of this approach. We further show that such toxicity can be circumvented
      and durable systemic antitumor immunity achieved by intratumoral delivery of an
      Fc-engineered anti-CD40 agonistic antibody.

PMID- 30297434
TI  - Reducing emergency hospital admissions: a population health complex intervention
      of an enhanced model of primary care and compassionate communities.
AB  - BACKGROUND: Reducing emergency admissions to hospital has been a cornerstone of
      healthcare policy. Little evidence exists to show that systematic interventions
      across a population have achieved this aim. The authors report the impact of a
      complex intervention over a 44-month period in Frome, Somerset, on unplanned
      admissions to hospital. AIM: To evaluate a population health complex intervention
      of an enhanced model of primary care and compassionate communities on population
      health improvement and reduction of emergency admissions to hospital. DESIGN AND
      SETTING: A cohort retrospective study of a complex intervention on all emergency
      admissions in Frome Medical Practice, Somerset, compared with the remainder of
      Somerset, from April 2013 to December 2017. METHOD: Patients were identified
      using broad criteria, including anyone giving cause for concern. Patient-centred
      goal setting and care planning combined with a compassionate community social
      approach was implemented broadly across the population of Frome. RESULTS: There
      was a progressive reduction, by 7.9 cases per quarter (95% confidence interval
      [CI] = 2.8 to 13.1, P = 0.006), in unplanned hospital admissions across the whole
      population of Frome during the study period from April 2013 to December 2017, a
      decrease of 14.0%. At the same time, there was a 28.5% increase in admissions per
      quarter within Somerset, with a rise in the number of unplanned admissions of 236
      per quarter (95% CI = 152 to 320, P<0.001). CONCLUSION: The complex intervention
      in Frome was associated with highly significant reductions in unplanned
      admissions to hospital, with a decrease in healthcare costs across the whole
      population of Frome.

PMID- 30297433
TI  - Regnase-1 controls colon epithelial regeneration via regulation of mTOR and
      purine metabolism.
AB  - Damage to intestinal epithelial cell (IEC) layers during intestinal inflammation
      is associated with inflammatory bowel disease. Here we show that the
      endoribonuclease Regnase-1 controls colon epithelial regeneration by regulating
      protein kinase mTOR (the mechanistic target of rapamycin kinase) and purine
      metabolism. During dextran sulfate sodium-induced intestinal epithelial injury
      and acute colitis, Regnase-1?IEC mice, which lack Regnase-1 specifically in the
      intestinal epithelium, were resistant to body weight loss, maintained an intact
      intestinal barrier, and showed increased cell proliferation and decreased
      epithelial apoptosis. Chronic colitis and tumor progression were also attenuated
      in Regnase-1?IEC mice. Regnase-1 predominantly regulates mTORC1 signaling.
      Metabolic analysis revealed that Regnase-1 participates in purine metabolism and
      energy metabolism during inflammation. Furthermore, increased expression of
      ectonucleotidases contributed to the resolution of acute inflammation in Regnase
      1?IEC mice. These findings provide evidence that Regnase-1 deficiency has
      beneficial effects on the prevention and/or blocking of intestinal inflammatory
      disorders.

PMID- 30297435
TI  - Attitudes towards faecal immunochemical testing in patients at increased risk of
      colorectal cancer: an online survey of GPs in England.
AB  - BACKGROUND: There is increasing interest in using a quantitative faecal
      immunochemical test (FIT) to rule out colorectal cancer (CRC) in patients with
      high-risk symptoms in primary care. AIM: This study aimed to investigate GPs'
      attitudes and willingness to use a FIT over an urgent 2-week wait (2WW) referral.
      DESIGN AND SETTING: A cross-sectional online survey involving 1024 GPs working
      across England. METHOD: Logistic regression models were used to explore the
      likelihood of GPs using a FIT instead of a 2WW referral, and reported using odds
      ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Just over one-third
      of GPs (n = 365) preferred to use a FIT as a rule-out test over a 2WW referral.
      GPs were more willing if they were: aged 36-45 years (OR 1.59 [95% CI = 1.04 to
      2.44]); 46-55 years (OR 1.99 [95% CI = 1.14 to 3.47]); thought a FIT was highly
      accurate (OR 1.63 [95% CI = 1.16 to 2.29]); thought patients would benefit
      compared with having a colonoscopy (OR 2.02 [95% CI = 1.46 to 2.79]); and were
      highly confident about discussing the benefits of a FIT (OR 2.14 [95% CI = 1.46
      to 3.16]). GPs were less willing if they had had >10 urgent referrals in the past
      year (OR 0.62 [95% CI = 0.40 to 0.94]) and thought that longer consultations
      would be needed (OR 0.61 [95% CI = 0.44 to 0.83]). CONCLUSION: The study findings
      suggest that the acceptability of using a FIT as a rule-out test in primary care
      is currently low, with less than half of GPs who perceived the test to be
      accurate preferring it over colonoscopy. Any potential guideline changes
      recommending a FIT in patients with high-risk symptoms, instead of urgent
      referral to rule out CRC, are likely to require intensive supporting educational
      outreach to increase GP confidence in the accuracy and application of a FIT in
      this context.

PMID- 30297436
TI  - Professional resilience in GPs working in areas of socioeconomic deprivation: a
      qualitative study in primary care.
AB  - BACKGROUND: GPs working in areas of high socioeconomic deprivation face
      particular challenges, and are at increased risk of professional burnout.
      Understanding how GPs working in such areas perceive professional resilience is
      important in order to recruit and retain a GP workforce in these areas. AIM: To
      understand how GPs working in areas of high socioeconomic deprivation consider
      professional resilience. DESIGN AND SETTING: A qualitative study of GPs
      practising in deprived areas within one primary care region of England. METHOD:
      In total, 14 individual interviews and one focus group of eight participants were
      undertaken, with sampling to data saturation. A framework approach was used for
      data analysis. RESULTS: Participants described three key themes relating to
      resilience. First, resilience was seen as involving flexibility and adaptability.
      This involved making trade-offs in order to keep going, even if this was
      imperfect. Second, resilience was enacted through teams rather than through
      individual strength. Third, resilience required the integration of personal and
      professional values rather than keeping the two separate. This dynamic adaptive
      view, with an emphasis on the importance of individuals within teams rather than
      in isolation, contrasts with the discourse of resilience as a personal
      characteristic, which should be strengthened at the individual level. CONCLUSION:
      Professional resilience is about more than individual strength. Policies to
      promote professional resilience, particularly in settings such as areas of high
      socioeconomic deprivation, must recognise the importance of flexibility,
      adaptability, working as teams, and successful integration between work and
      personal values.

PMID- 30297437
TI  - GP follow-up after first diagnosing psychological problems among adolescents: a
      nationwide register-based study.
AB  - BACKGROUND: Psychological problems are common among adolescents. Many GPs
      consider these problems challenging, even after diagnosis. AIM: To explore how
      Norwegian GPs follow-up patients after a first diagnosis of a psychological
      problem at age 15-16 years. DESIGN AND SETTING: Nationwide longitudinal, register
      based study using claims data for all GPs in the national list patient system,
      and for adolescents born in 1993 and 1994 (n = 129 499). METHOD: National
      databases and registers were used to determine how many adolescents received a
      first diagnosis of a psychological problem in a GP consultation at age 15 or 16
      years. Further consultations, collaborative contacts in primary care, and
      referrals to secondary care during the year after diagnosis were then identified
      and used as outcomes in regression analyses to investigate associations with
      initial diagnosis, parental education, and GP characteristics. RESULTS: In total,
      6809 (5.3%) adolescents received a first diagnosis of a psychological problem in
      a GP consultation at age 15 or 16 years. Internalising problems constituted 50.5%
      of initial diagnoses among females and 28.8% among males. Behaviour and attention
      problems accounted for 21.3% for females and 45.0% for males. In total, 46.6% of
      females and 39.9% of males had >=1 follow-up consultation, and 32.8% of females
      and 27.0% of males were referred to secondary care. GPs reported primary care
      collaboration for 22.1% of females and 19.1% of males. GPs with larger patient
      lists had higher referral rates, but collaborated less within primary care. Males
      with a male GP had more follow-up consultations than males with a female GP.
      CONCLUSION: GP follow-up after diagnosing psychological problems among
      adolescents is limited, but predominantly comprised referrals and some
      multidisciplinary cooperation. GP follow-up consultations should be studied more
      thoroughly, and the role of GPs warrants further policy discussions.

PMID- 30297438
TI  - Tight junction proteins in gastrointestinal and liver disease.
AB  - Over the past two decades a growing body of evidence has demonstrated an
      important role of tight junction (TJ) proteins in the physiology and disease
      biology of GI and liver disease. On one side, TJ proteins exert their functional
      role as integral proteins of TJs in forming barriers in the gut and the liver.
      Furthermore, TJ proteins can also be expressed outside TJs where they play
      important functional roles in signalling, trafficking and regulation of gene
      expression. A hallmark of TJ proteins in disease biology is their functional role
      in epithelial-to-mesenchymal transition. A causative role of TJ proteins has been
      established in the pathogenesis of colorectal cancer and gastric cancer. Among
      the best characterised roles of TJ proteins in liver disease biology is their
      function as cell entry receptors for HCV-one of the most common causes of
      hepatocellular carcinoma. At the same time TJ proteins are emerging as targets
      for novel therapeutic approaches for GI and liver disease. Here we review our
      current knowledge of the role of TJ proteins in the pathogenesis of GI and liver
      disease biology and discuss their potential as therapeutic targets.

PMID- 30297440
TI  - Milestone in congenital cardiac surgery: 65 years of the heart-lung machine.

PMID- 30297441
TI  - A call to action: attention to paediatric-specific disaster preparedness.

PMID- 30297439
TI  - Long term adjuvant endocrine therapy and risk of cardiovascular disease in female
      breast cancer survivors: systematic review.
AB  - OBJECTIVE: To investigate the effect of endocrine therapies on a wide range of
      specific clinical cardiovascular disease outcomes in women with a history of non
      metastatic breast cancer. DESIGN: Systematic review and meta-analysis of
      randomised controlled trials and observational studies. DATA SOURCES: Medline and
      Embase up until June 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies
      were included if they investigated the risk of a specific cardiovascular disease
      outcome associated with use of either tamoxifen or an aromatase inhibitor, or
      compared the two treatments, in women with a history of non-metastatic breast
      cancer. APPRAISAL AND DATA EXTRACTION: Relevant studies were originally
      identified and results extracted by one researcher, with a full replication of
      the study identification process by a combination of two other researchers. The
      Cochrane Collaboration's tool for assessing risk of bias was used to assess risk
      of bias in randomised controlled trials, and this tool was adapted to assess risk
      of bias in observational studies. RESULTS: 26 studies were identified, with
      results for seven specific cardiovascular disease outcomes (venous
      thromboembolism, myocardial infarction, stroke, angina, heart failure,
      arrhythmia, and peripheral vascular disease). Results suggested an increased risk
      of venous thromboembolism in tamoxifen users compared with both non-users and
      aromatase inhibitor users. Results were also consistent with a higher risk of the
      vascular diseases myocardial infarction and angina in aromatase inhibitor users
      compared with tamoxifen users, but there was also a suggestion that this may be
      partly driven by a protective effect of tamoxifen on these outcomes. Data were
      limited, and evidence was generally inconsistent for all other cardiovascular
      disease outcomes. CONCLUSION: This review has collated substantial randomised
      controlled trial and observational evidence on the effect of endocrine therapies
      on several specific cardiovascular disease outcomes including venous
      thromboembolism and myocardial infarction, progressing knowledge. Although the
      choice of aromatase inhibitor or tamoxifen will primarily be based on the
      effectiveness against the recurrence of breast cancer, this review shows that the
      individual patient's risk of venous or arterial vascular disease should be an
      important secondary consideration. SYSTEMATIC REVIEW REGISTRATION: Prospero
      CRD42017065944.

PMID- 30297442
TI  - Can infant sleeping bags be recommended by medical professionals as protection
      against sudden infant death syndrome?
AB  - : Clinical scenario: A mother brought her infant to the hospital with
      bronchiolitis and incidentally asked if I would recommend the use of infant
      sleeping bags to protect against Sudden Infant Death Syndrome as several of her
      friends use them. Structured question: Can infant sleeping bags be recommended by
      medical professionals as protective against Sudden Infant Death Syndrome?
      METHODS: A literature search was performed. Trials were included if they had an
      English version available and the papers examined the impact that sleeping bag
      use had on risk of SIDS or its risk factors. Cochrane Library search found eight
      trials, two of which were found to meet inclusion criteria. MEDLINE was searched
      using the search terms ((baby sleeping bag) OR infant sleeping bag) OR cotton
      sleeping sack. Forty-seven papers were found, two of which were found to meet the
      inclusion criteria, one of which had already been found in the Cochrane Library
      search. One further paper was found through searching citations of the papers
      included. DISCUSSION: Sleeping bags are used in 48-95% of infants in the UK and
      advocated for by the Lullaby Trust for their safety in the prevention of SIDS.
      The case control studies included found that sleeping bags are as safe, if not
      safer than other bedding when examining SIDS as an outcome. For sleeping bags to
      be safe they must be well made and appropriately used, which includes the correct
      size, Tog, clothing and other bedding for bedroom temperature.

PMID- 30297443
TI  - Does immobilisation improve outcomes in children with a toddler's fracture?

PMID- 30297444
TI  - Prediction of school outcome after preterm birth: a cohort study.
AB  - OBJECTIVE: To identify if the educational trajectories of preterm infants differ
      from those of their term peers. DESIGN: This work is based on the Avon
      Longitudinal Study of Parents and Children (ALSPAC). Educational measures were
      categorised into 10 deciles to allow comparison of measures across time periods.
      Gestational age was categorised as preterm (23-36 weeks) or term (37-42 weeks).
      Multilevel mixed-effects linear regression models were derived to examine the
      trajectories of decile scores across the study period. Gestational group was
      added as an interaction term to assess if the trajectory between educational
      measures varied between preterm and term infants. Adjustment for possible
      confounders was performed. SUBJECTS: The final dataset contained information on
      12 586 infants born alive at between 23 weeks and 42 weeks of gestation. MAIN
      OUTCOME MEASURES: UK mandatory educational assessments (SATs) scores throughout
      educational journal (including final GCSE results at 16 years of age). RESULTS:
      Preterm infants had on average lower Key Stage (KS) scores than term children (
      0.46 (-0.84 to -0.07)). However, on average, they gained on their term peers in
      each progressive measure (0.10 (0.01 to 0.19)), suggesting 'catch up' during the
      first few years at school. Preterm infants appeared to exhibit the increase in
      decile scores mostly between KS1 and KS2 (p=0.005) and little between KS2 and KS3
      (p=0.182) or KS3 and KS4 (p=0.149). CONCLUSIONS: This work further emphasises the
      importance of early schooling and environment in these infants and suggests that
      support, long after the premature birth, may have additional benefits.

PMID- 30297445
TI  - Non-adherence to prescribing guidelines for reduced kidney function puts older
      people at risk.
AB  - Review of: Wood S et al Application of prescribing recommendations in older
      people with reduced kidney function: a cross-sectional study in general practice.
      Br J Gen Practice 2018; 68: e378-87.

PMID- 30297446
TI  - MHRA Drug Safety Update: denosumab (Xgeva) and rebound hypercalcaemia.
AB  - Review of: Medical and Healthcare products Regulatory Agency. Denosumab for giant
      cell tumor of bone: risk of clinically significant hypercalcaemia following
      discontinuation. Drug Safety Update 2018;11(11);2.

PMID- 30297447
TI  - Audit of COPD exacerbations in secondary care.
AB  - Review of: Review of: Stone RA et al COPD: working together. National Chronic
      Obstructive Pulmonary Disease (COPD) Audit Programme: clinical audit of COPD
      exacerbations admitted to acute hospitals in England and Wales. 2017 National
      Clinical Audit Report. London. RCP, April 2018.

PMID- 30297448
TI  - Five-day nitrofurantoin is better than single-dose fosfomycin at resolving UTI
      symptoms.
AB  - Review of: Huttner A et al Effect of 5-day nitrofurantoin vs single dose
      fosfomycin on clinical resolution of uncomplicated lower urinary tract infection
      in women. JAMA 2018;319(17):1781-9.

PMID- 30297449
TI  - Ulipristal acetate (Esmya): restrictions on use.
AB  - Safety alert: Esmya (ulipristal acetate) for symptoms of uterine fibroids:
      restrictions to use and requirement to check liver function before, during and
      after treatment.1,2.

PMID- 30297450
TI  - Ideal model of care for multimorbidity: the search continues.

PMID- 30297451
TI  - Exercise is an important intervention for treating intermittent claudication.
AB  - Review of: Lane R et al Exercise for intermittent claudication. Cochrane Database
      of Syst Revs 2017;12:10.1002/14651858.CD000990.pub4.

PMID- 30297452
TI  - Does melatonin improve sleep in children with neurodevelopmental disorders?
AB  - Review of: Abdelgadir IS et al Melatonin for the management of sleep problems in
      children with neurodevelopmental disorders: a systematic review and meta
      analysis. Archives Dis Child 2018. doi: 10.1136/archdischild-2017-314181. [Epub
      ahead of print 2 May 2018].

PMID- 30297453
TI  - PRP4KA, a Putative Spliceosomal Protein Kinase, Is Important for Alternative
      Splicing and Development in Arabidopsis thaliana.
AB  - Splicing of precursor messenger RNAs (pre-mRNAs) is an essential step in the
      expression of most eukaryotic genes. Both constitutive splicing and alternative
      splicing, which produces multiple messenger RNA (mRNA) isoforms from a single
      primary transcript, are modulated by reversible protein phosphorylation. Although
      the plant splicing machinery is known to be a target for phosphorylation, the
      protein kinases involved remain to be fully defined. We report here the
      identification of pre-mRNA processing 4 (PRP4) KINASE A (PRP4KA) in a forward
      genetic screen based on an alternatively spliced GFP reporter gene in Arabidopsis
      thaliana (Arabidopsis). Prp4 kinase is the first spliceosome-associated kinase
      shown to regulate splicing in fungi and mammals but it has not yet been studied
      in plants. In the same screen we identified mutants defective in SAC3A, a
      putative mRNA export factor that is highly coexpressed with PRP4KA in Arabidopsis
      Whereas the sac3a mutants appear normal, the prp4ka mutants display a pleiotropic
      phenotype featuring atypical rosettes, late flowering, tall final stature,
      reduced branching, and lowered seed set. Analysis of RNA-sequencing data from
      prp4ka and sac3a mutants identified widespread and partially overlapping
      perturbations in alternative splicing in the two mutants. Quantitative
      phosphoproteomic profiling of a prp4ka mutant detected phosphorylation changes in
      several serine/arginine-rich proteins, which regulate constitutive and
      alternative splicing, and other splicing-related factors. Tests of PRP4KB, the
      paralog of PRP4KA, indicated that the two genes are not functionally redundant.
      The results demonstrate the importance of PRP4KA for alternative splicing and
      plant phenotype, and suggest that PRP4KA may influence alternative splicing
      patterns by phosphorylating a subset of splicing regulators.

PMID- 30297454
TI  - Combinatorial Approach for Complex Disorder Prediction: Case Study of
      Neurodevelopmental Disorders.
AB  - Early prediction of complex disorders (e.g., autism and other neurodevelopmental
      disorders) is one of the fundamental goals of precision medicine and personalized
      genomics. An early prediction of complex disorders can improve the prognosis,
      increase the effectiveness of interventions and treatments, and enhance the life
      quality of affected patients. Considering the genetic heritability of
      neurodevelopmental disorders, we are proposing a novel framework for utilizing
      rare coding variation for early prediction of these disorders in subset of
      affected samples. We provide a combinatorial framework for addressing this
      problem, denoted as Odin (Oracle for DIsorder predictioN), to make a prediction
      for a small, yet significant, subset of affected cases while having very low
      false positive rate (FPR) prediction for unaffected samples. Odin also takes
      advantage of the available functional information (e.g., pairwise coexpression of
      genes during brain development) to increase the prediction power beyond genes
      with recurrent variants. Application of our method accurately recovers an
      additional 8% of autism cases without any severe variant in known recurrent
      mutated genes with a <1% FPR. Furthermore, Odin predicted a set of 391 genes that
      severe variants in these genes can cause autism or other developmental delay
      disorders. Approaches such as the one presented in this paper are needed to
      translate the biomedical discoveries into actionable items by clinicians. Odin is
      publicly available at https://github.com/HormozdiariLab/Odin.

PMID- 30297457
TI  - GPs and technology: the good, the bad, and the ugly babies.

PMID- 30297456
TI  - Reconfigured Cyanogenic Glucoside Biosynthesis in Eucalyptus cladocalyx Involves
      a Cytochrome P450 CYP706C55.
AB  - Cyanogenic glucosides are a class of specialized metabolites widespread in the
      plant kingdom. Cyanogenic glucosides are alpha-hydroxynitriles, and their
      hydrolysis releases toxic hydrogen cyanide, providing an effective chemical
      defense against herbivores. Eucalyptus cladocalyx is a cyanogenic tree,
      allocating up to 20% of leaf nitrogen to the biosynthesis of the cyanogenic
      monoglucoside, prunasin. Here, mass spectrometry analyses of E. cladocalyx
      tissues revealed spatial and ontogenetic variations in prunasin content, as well
      as the presence of the cyanogenic diglucoside amygdalin in flower buds and
      flowers. The identification and biochemical characterization of the prunasin
      biosynthetic enzymes revealed a unique enzyme configuration for prunasin
      production in E. cladocalyx This result indicates that a multifunctional
      cytochrome P450 (CYP), CYP79A125, catalyzes the initial conversion of l
      phenylalanine into its corresponding aldoxime, phenylacetaldoxime; a function
      consistent with other members of the CYP79 family. In contrast to the single
      multifunctional CYP known from other plant species, the conversion of
      phenylacetaldoxime to the alpha-hydroxynitrile, mandelonitrile, is catalyzed by
      two distinct CYPs. CYP706C55 catalyzes the dehydration of phenylacetaldoxime, an
      unusual CYP reaction. The resulting phenylacetonitrile is subsequently
      hydroxylatedby CYP71B103 to form mandelonitrile. The final glucosylation step to
      yield prunasin is catalyzed by a UDP-glucosyltransferase, UGT85A59. Members of
      the CYP706 family have not been reported previously to participate in the
      biosynthesis of cyanogenic glucosides, and the pathway structure in E. cladocalyx
      represents an example of convergent evolution in the biosynthesis of cyanogenic
      glucosides in plants.

PMID- 30297458
TI  - Long-Term Survival in Patients Responding to Anti-PD-1/PD-L1 Therapy and Disease
      Outcome upon Treatment Discontinuation.
AB  - Purpose: Anti-PD-(L)1 can provide overall survival (OS) benefits over
      conventional treatments for patients with many different cancer types. However,
      the long-term outcome of cancer patients responding to these therapies remains
      unknown. This study is an exploratory study that aimed to describe the long-term
      survival of patients responding to anti-PD-(L)1 monotherapy across multiple
      cancer types.Experimental Design: Data from patients treated with an anti-PD-(L)1
      monotherapy in a phase I trial at Gustave Roussy were retrospectively analyzed
      over a period of 5 years. All cancer types (n = 19) were included. Clinical and
      biological factors associated with response, long-term survival, and secondary
      refractory disease were studied.Results: Among 262 eligible patients, the overall
      objective response rate was 29%. The median progression-free survival of
      responder patients (RP) at 3 months was 30 months, and the median OS of RP was
      not reached after a median follow-up of 34 months. In RPs, 3- and 5-year OS
      percentages were 84% and 64%, respectively. No death occurred in the 21 complete
      responders (CR) during the overall follow-up. However, many partial responders
      (PR) showed subsequent tumor relapses to treatment. Long responders (response >=2
      years) represented 11.8% of the overall population. These findings should be
      validated in further prospective studies.Conclusions: There are currently no
      differences in therapeutic strategies between CRs and PRs to anti-PD-(L)1. We
      found a striking difference in OS between these two types of responses. Our
      results are in favor of evaluating patient stratification strategies and
      intensification of treatments when tumor lesions of a partial responder to
      immunotherapy stop improving. Clin Cancer Res; 1-11. (c)2018 AACR.

PMID- 30297459
TI  - Phosphorylation of TIP60 suppresses 53BP1 localization at DNA damage sites.
AB  - Proper balance between the repair of DNA double-strand breaks (DSBs) by
      homologous recombination and nonhomologous end-joining is critical for
      maintaining genome integrity and preventing tumorigenesis. This balance is
      regulated and fine-tuned by a variety of factors, including cell cycle and the
      chromatin environment. The histone acetyltransferase TIP60 was previously shown
      to suppress pathologic end-joining and promote homologous recombination. However,
      it is unknown how regulatory post-translational modifications impact TIP60
      acetyltransferase activity to influence the outcome of DSB responses. In this
      study we report that phosphorylation of TIP60 on serines 90 and 86 is important
      for limiting the accumulation of the pro-end-joining factor 53BP1 at DSBs in S
      and G2 cell cycle phases. Mutation of these sites disrupts histone acetylation
      changes in response to DNA damage, BRCA1 localization to DSBs, and PARP inhibitor
      resistance. These findings reveal that phosphorylation directs TIP60-dependent
      acetylation to promote homologous recombination and maintain genome stability.

PMID- 30297455
TI  - Elucidation of the Amygdalin Pathway Reveals the Metabolic Basis of Bitter and
      Sweet Almonds (Prunus dulcis).
AB  - Almond (Prunus dulcis) is the principal Prunus species in which the consumed and
      thus commercially important part of the fruit is the kernel. As a result of
      continued selection, the vast majority of almonds have a nonbitter kernel.
      However, in the field, there are trees carrying bitter kernels, which are toxic
      to humans and, consequently, need to be removed. The toxicity of bitter almonds
      is caused by the accumulation of the cyanogenic diglucoside amygdalin, which
      releases toxic hydrogen cyanide upon hydrolysis. In this study, we identified and
      characterized the enzymes involved in the amygdalin biosynthetic pathway:
      PdCYP79D16 and PdCYP71AN24 as the cytochrome P450 (CYP) enzymes catalyzing
      phenylalanine-to-mandelonitrile conversion, PdUGT94AF3 as an additional
      monoglucosyl transferase (UGT) catalyzing prunasin formation, and PdUGT94AF1 and
      PdUGT94AF2 as the two enzymes catalyzing amygdalin formation from prunasin. This
      was accomplished by constructing a sequence database containing UGTs known, or
      predicted, to catalyze a beta(1->6)-O-glycosylation reaction and a Basic Local
      Alignment Search Tool search of the draft version of the almond genome versus
      these sequences. Functional characterization of candidate genes was achieved by
      transient expression in Nicotiana benthamiana Reverse transcription quantitative
      polymerase chain reaction demonstrated that the expression of PdCYP79D16 and
      PdCYP71AN24 was not detectable or only reached minute levels in the sweet almond
      genotype during fruit development, while it was high and consistent in the bitter
      genotype. Therefore, the basis for the sweet kernel phenotype is a lack of
      expression of the genes encoding the two CYPs catalyzing the first steps in
      amygdalin biosynthesis.

PMID- 30297460
TI  - New insights into the variability of the tropical land carbon cycle from the El
      Nino of 2015/2016.

PMID- 30297462
TI  - A successful prediction of the record CO2 rise associated with the 2015/2016 El
      Nino.
AB  - In early 2016, we predicted that the annual rise in carbon dioxide concentration
      at Mauna Loa would be the largest on record. Our forecast used a statistical
      relationship between observed and forecast sea surface temperatures in the Nino
      3.4 region and the annual CO2 rise. Here, we provide a formal verification of
      that forecast. The observed rise of 3.4 ppm relative to 2015 was within the
      forecast range of 3.15 +/- 0.53 ppm, so the prediction was successful. A global
      terrestrial biosphere model supports the expectation that the El Nino weakened
      the tropical land carbon sink. We estimate that the El Nino contributed
      approximately 25% to the record rise in CO2, with 75% due to anthropogenic
      emissions. The 2015/2016 CO2 rise was greater than that following the previous
      large El Nino in 1997/1998, because anthropogenic emissions had increased. We had
      also correctly predicted that 2016 would be the first year with monthly mean CO2
      above 400 ppm all year round. We now estimate that atmospheric CO2 at Mauna Loa
      would have remained above 400 ppm all year round in 2016 even if the El Nino had
      not occurred, contrary to our previous expectations based on a simple
      extrapolation of previous trends.This article is part of a discussion meeting
      issue 'The impact of the 2015/2016 El Nino on the terrestrial tropical carbon
      cycle: patterns, mechanisms and implications'.

PMID- 30297461
TI  - Spatio-temporal patterns of thermal anomalies and drought over tropical forests
      driven by recent extreme climatic anomalies.
AB  - The recent 2015-2016 El Nino (EN) event was considered as strong as the EN in
      1997-1998. Given such magnitude, it was expected to result in extreme warming and
      moisture anomalies in tropical areas. Here we characterize the spatial patterns
      of temperature anomalies and drought over tropical forests, including tropical
      South America (Amazonia), Africa and Asia/Indonesia during the 2015-2016 EN
      event. These spatial patterns of warming and drought are compared with those
      observed in previous strong EN events (1982-1983 and 1997-1998) and other
      moderate to strong EN events (e.g. 2004-2005 and 2009-2010). The link between the
      spatial patterns of drought and sea surface temperature anomalies in the central
      and eastern Pacific is also explored. We show that indeed the EN2015-2016 led to
      unprecedented warming compared to the other EN events over Amazonia, Africa and
      Indonesia, as a consequence of the background global warming trend. Anomalous
      accumulated extreme drought area over Amazonia was found during EN2015-2016, but
      this value may be closer to extreme drought area extents in the other two EN
      events in 1982-1983 and 1997-1998. Over Africa, datasets disagree, and it is
      difficult to conclude which EN event led to the highest accumulated extreme
      drought area. Our results show that the highest values of accumulated drought
      area over Africa were obtained in 2015-2016 and 1997-1998, with a long-term
      drying trend not observed over the other tropical regions. Over Indonesia, all
      datasets suggest that EN 1982-1983 and EN 1997-1998 (or even the drought of 2005)
      led to a higher extreme drought area than EN2015-2016. Uncertainties in
      precipitation datasets hinder consistent estimates of drought severity over
      tropical regions, and improved reanalysis products and station records are
      required.This article is part of a discussion meeting issue 'The impact of the
      2015/2016 El Nino on the terrestrial tropical carbon cycle: patterns, mechanisms
      and implications'.

PMID- 30297464
TI  - History of El Nino impacts on the global carbon cycle 1957-2017: a quantification
      from atmospheric CO2 data.
AB  - Interannual variations in the large-scale net ecosystem exchange (NEE) of CO2
      between the terrestrial biosphere and the atmosphere were estimated for 1957-2017
      from sustained measurements of atmospheric CO2 mixing ratios. As the observations
      are sparse in the early decades, available records were combined into a 'quasi
      homogeneous' dataset based on similarity in their signals, to minimize spurious
      variations from beginning or ending data records. During El Nino events, CO2 is
      anomalously released from the tropical band, and a few months later also in the
      northern extratropical band. This behaviour can approximately be represented by a
      linear relationship of the NEE anomalies and local air temperature anomalies,
      with sensitivity coefficients depending on geographical location and season. The
      apparent climate sensitivity of global total NEE against variations in pan
      tropically averaged annual air temperature slowly changed over time during the
      1957-2017 period, first increasing (though less strongly than in previous
      studies) but then decreasing again. However, only part of this change can be
      attributed to actual changes in local physiological or ecosystem processes, the
      rest probably arising from shifts in the geographical area of dominating
      temperature variations.This article is part of a discussion meeting issue 'The
      impact of the 2015/2016 El Nino on the terrestrial tropical carbon cycle:
      patterns, mechanisms and implications'.

PMID- 30297463
TI  - Tropical land carbon cycle responses to 2015/16 El Nino as recorded by
      atmospheric greenhouse gas and remote sensing data.
AB  - The outstanding tropical land climate characteristic over the past decades is
      rapid warming, with no significant large-scale precipitation trends. This warming
      is expected to continue but the effects on tropical vegetation are unknown. El
      Nino-related heat peaks may provide a test bed for a future hotter world. Here we
      analyse tropical land carbon cycle responses to the 2015/16 El Nino heat and
      drought anomalies using an atmospheric transport inversion. Based on the global
      atmospheric CO2 and fossil fuel emission records, we find no obvious signs of
      anomalously large carbon release compared with earlier El Nino events, suggesting
      resilience of tropical vegetation. We find roughly equal net carbon release
      anomalies from Amazonia and tropical Africa, approximately 0.5 PgC each, and
      smaller carbon release anomalies from tropical East Asia and southern Africa.
      Atmospheric CO anomalies reveal substantial fire carbon release from tropical
      East Asia peaking in October 2015 while fires contribute only a minor amount to
      the Amazonian carbon flux anomaly. Anomalously large Amazonian carbon flux
      release is consistent with downregulation of primary productivity during peak
      negative near-surface water anomaly (October 2015 to March 2016) as diagnosed by
      solar-induced fluorescence. Finally, we find an unexpected anomalous positive
      flux to the atmosphere from tropical Africa early in 2016, coincident with
      substantial CO release.This article is part of a discussion meeting issue 'The
      impact of the 2015/2016 El Nino on the terrestrial tropical carbon cycle:
      patterns, mechanisms and implications'.

PMID- 30297466
TI  - Monitoring emissions from the 2015 Indonesian fires using CO satellite data.
AB  - Southeast Asia, in particular Indonesia, has periodically struggled with intense
      fire events. These events convert substantial amounts of carbon stored as peat to
      atmospheric carbon dioxide (CO2) and significantly affect atmospheric composition
      on a regional to global scale. During the recent 2015 El Nino event, peat fires
      led to strong enhancements of carbon monoxide (CO), an air pollutant and well
      known tracer for biomass burning. These enhancements were clearly observed from
      space by the Infrared Atmospheric Sounding Interferometer (IASI) and the
      Measurements of Pollution in the Troposphere (MOPITT) instruments. We use these
      satellite observations to estimate CO fire emissions within an inverse modelling
      framework. We find that the derived CO emissions for each sub-region of Indonesia
      and Papua are substantially different from emission inventories, highlighting
      uncertainties in bottom-up estimates. CO fire emissions based on either MOPITT or
      IASI have a similar spatial pattern and evolution in time, and a 10% uncertainty
      based on a set of sensitivity tests we performed. Thus, CO satellite data have a
      high potential to complement existing operational fire emission estimates based
      on satellite observations of fire counts, fire radiative power and burned area,
      in better constraining fire occurrence and the associated conversion of peat
      carbon to atmospheric CO2 A total carbon release to the atmosphere of 0.35-0.60
      Pg C can be estimated based on our results.This article is part of a discussion
      meeting issue 'The impact of the 2015/2016 El Nino on the terrestrial tropical
      carbon cycle: patterns, mechanisms and implications'.

PMID- 30297465
TI  - Impact of the 2015/2016 El Nino on the terrestrial carbon cycle constrained by
      bottom-up and top-down approaches.
AB  - Evaluating the response of the land carbon sink to the anomalies in temperature
      and drought imposed by El Nino events provides insights into the present-day
      carbon cycle and its climate-driven variability. It is also a necessary step to
      build confidence in terrestrial ecosystems models' response to the warming and
      drying stresses expected in the future over many continents, and particularly in
      the tropics. Here we present an in-depth analysis of the response of the
      terrestrial carbon cycle to the 2015/2016 El Nino that imposed extreme warming
      and dry conditions in the tropics and other sensitive regions. First, we provide
      a synthesis of the spatio-temporal evolution of anomalies in net land-atmosphere
      CO2 fluxes estimated by two in situ measurements based on atmospheric inversions
      and 16 land-surface models (LSMs) from TRENDYv6. Simulated changes in ecosystem
      productivity, decomposition rates and fire emissions are also investigated.
      Inversions and LSMs generally agree on the decrease and subsequent recovery of
      the land sink in response to the onset, peak and demise of El Nino conditions and
      point to the decreased strength of the land carbon sink: by 0.4-0.7 PgC yr-1
      (inversions) and by 1.0 PgC yr-1 (LSMs) during 2015/2016. LSM simulations
      indicate that a decrease in productivity, rather than increase in respiration,
      dominated the net biome productivity anomalies in response to ENSO throughout the
      tropics, mainly associated with prolonged drought conditions.This article is part
      of a discussion meeting issue 'The impact of the 2015/2016 El Nino on the
      terrestrial tropical carbon cycle: patterns, mechanisms and implications'.

PMID- 30297467
TI  - Tree growth and stem carbon accumulation in human-modified Amazonian forests
      following drought and fire.
AB  - Human-modified forests are an ever-increasing feature across the Amazon Basin,
      but little is known about how stem growth is influenced by extreme climatic
      events and the resulting wildfires. Here we assess for the first time the impacts
      of human-driven disturbance in combination with El Nino-mediated droughts and
      fires on tree growth and carbon accumulation. We found that after 2.5 years of
      continuous measurements, there was no difference in stem carbon accumulation
      between undisturbed and human-modified forests. Furthermore, the extreme drought
      caused by the El Nino did not affect carbon accumulation rates in surviving
      trees. In recently burned forests, trees grew significantly more than in unburned
      ones, regardless of their history of previous human disturbance. Wood density was
      the only significant factor that helped explain the difference in growth between
      trees in burned and unburned forests, with low wood-density trees growing
      significantly more in burned sites. Our results suggest stem carbon accumulation
      is resistant to human disturbance and one-off extreme drought events, and it is
      stimulated immediately after wildfires. However, these results should be seen
      with caution-without accounting for carbon losses, recruitment and longer-term
      changes in species composition, we cannot fully understand the impacts of drought
      and fire in the carbon balance of human-modified forests.This article is part of
      a discussion meeting issue 'The impact of the 2015/2016 El Nino on the
      terrestrial tropical carbon cycle: patterns, mechanisms and implications'.

PMID- 30297468
TI  - Short-term effects of drought on tropical forest do not fully predict impacts of
      repeated or long-term drought: gas exchange versus growth.
AB  - Are short-term responses by tropical rainforest to drought (e.g. during El Nino)
      sufficient to predict changes over the long-term, or from repeated drought? Using
      the world's only long-term (16-year) drought experiment in tropical forest we
      examine predictability from short-term measurements (1-2 years). Transpiration
      was maximized in droughted forest: it consumed all available throughfall
      throughout the 16 years of study. Leaf photosynthetic capacity [Formula: see
      text] was maintained, but only when averaged across tree size groups. Annual
      transpiration in droughted forest was less than in control, with initial
      reductions (at high biomass) imposed by foliar stomatal control. Tree mortality
      increased after year three, leading to an overall biomass loss of 40%; over the
      long-term, the main constraint on transpiration was thus imposed by the
      associated reduction in sapwood area. Altered tree mortality risk may prove
      predictable from soil and plant hydraulics, but additional monitoring is needed
      to test whether future biomass will stabilize or collapse. Allocation of
      assimilate differed over time: stem growth and reproductive output declined in
      the short-term, but following mortality-related changes in resource availability,
      both showed long-term resilience, with partial or full recovery. Understanding
      and simulation of these phenomena and related trade-offs in allocation will
      advance more effectively through greater use of optimization and probabilistic
      modelling approaches.This article is part of a discussion meeting issue 'The
      impact of the 2015/2016 El Nino on the terrestrial tropical carbon cycle:
      patterns, mechanisms and implications'.

PMID- 30297469
TI  - Quantifying immediate carbon emissions from El Nino-mediated wildfires in humid
      tropical forests.
AB  - Wildfires produce substantial CO2 emissions in the humid tropics during El Nino
      mediated extreme droughts, and these emissions are expected to increase in coming
      decades. Immediate carbon emissions from uncontrolled wildfires in human-modified
      tropical forests can be considerable owing to high necromass fuel loads. Yet,
      data on necromass combustion during wildfires are severely lacking. Here, we
      evaluated necromass carbon stocks before and after the 2015-2016 El Nino in
      Amazonian forests distributed along a gradient of prior human disturbance. We
      then used Landsat-derived burn scars to extrapolate regional immediate wildfire
      CO2 emissions during the 2015-2016 El Nino. Before the El Nino, necromass stocks
      varied significantly with respect to prior disturbance and were largest in
      undisturbed primary forests (30.2 +/- 2.1 Mg ha-1, mean +/- s.e.) and smallest in
      secondary forests (15.6 +/- 3.0 Mg ha-1). However, neither prior disturbance nor
      our proxy of fire intensity (median char height) explained necromass losses due
      to wildfires. In our 6.5 million hectare (6.5 Mha) study region, almost 1 Mha of
      primary (disturbed and undisturbed) and 20 000 ha of secondary forest burned
      during the 2015-2016 El Nino. Covering less than 0.2% of Brazilian Amazonia,
      these wildfires resulted in expected immediate CO2 emissions of approximately 30
      Tg, three to four times greater than comparable estimates from global fire
      emissions databases. Uncontrolled understorey wildfires in humid tropical forests
      during extreme droughts are a large and poorly quantified source of CO2
      emissions.This article is part of a discussion meeting issue 'The impact of the
      2015/2016 El Nino on the terrestrial tropical carbon cycle: patterns, mechanisms
      and implications'.

PMID- 30297471
TI  - Inter-comparison and assessment of gridded climate products over tropical forests
      during the 2015/2016 El Nino.
AB  - To understand the impacts of extreme climate events, it is first necessary to
      understand the spatio-temporal characteristics of the event. Gridded climate
      products are frequently used to describe climate patterns but have been shown to
      perform poorly over data-sparse regions such as tropical forests. Often, they are
      uncritically employed in a wide range of studies linking tropical forest
      processes to large-scale climate variability. Here, we conduct an inter
      comparison and assessment of near-surface air temperature fields supplied by four
      state-of-the-art reanalysis products, along with precipitation estimates supplied
      by four merged satellite-gauge rainfall products. Firstly, spatio-temporal
      patterns of temperature and precipitation anomalies during the 2015-2016 El Nino
      are shown for each product to characterize the impact of the El Nino on the
      tropical forest biomes of Equatorial Africa, Southeast Asia and South America.
      Using meteorological station data, a two-stage assessment is then conducted to
      determine which products most reliably model tropical climates during the 2015
      2016 El Nino, and which perform best over the longer-term satellite observation
      period (1980-2016). Results suggest that eastern Amazonia, parts of the Congo
      Basin and mainland Southeast Asia all experienced significant monthly mean
      temperature anomalies during the El Nino, while northeastern Amazonia, eastern
      Borneo and southern New Guinea experienced significant precipitation deficits.
      Our results suggest ERA-Interim and MERRA2 are the most reliable air temperature
      datasets, while TRMM 3B42 V7 and CHIRPS v2.0 are the best-performing rainfall
      datasets.This article is part of a discussion meeting issue 'The impact of the
      2015/2016 El Nino on the terrestrial tropical carbon cycle: patterns, mechanisms
      and implications'.

PMID- 30297470
TI  - Modelling tropical forest responses to drought and El Nino with a stomatal
      optimization model based on xylem hydraulics.
AB  - The current generation of dynamic global vegetation models (DGVMs) lacks a
      mechanistic representation of vegetation responses to soil drought, impairing
      their ability to accurately predict Earth system responses to future climate
      scenarios and climatic anomalies, such as El Nino events. We propose a simple
      numerical approach to model plant responses to drought coupling stomatal
      optimality theory and plant hydraulics that can be used in dynamic global
      vegetation models (DGVMs). The model is validated against stand-scale forest
      transpiration (E) observations from a long-term soil drought experiment and used
      to predict the response of three Amazonian forest sites to climatic anomalies
      during the twentieth century. We show that our stomatal optimization model
      produces realistic stomatal responses to environmental conditions and can
      accurately simulate how tropical forest E responds to seasonal, and even long
      term soil drought. Our model predicts a stronger cumulative effect of climatic
      anomalies in Amazon forest sites exposed to soil drought during El Nino years
      than can be captured by alternative empirical drought representation schemes. The
      contrasting responses between our model and empirical drought factors highlight
      the utility of hydraulically-based stomatal optimization models to represent
      vegetation responses to drought and climatic anomalies in DGVMs.This article is
      part of a discussion meeting issue 'The impact of the 2015/2016 El Nino on the
      terrestrial tropical carbon cycle: patterns, mechanisms and implications'.

PMID- 30297472
TI  - The role of satellite observations in understanding the impact of El Nino on the
      carbon cycle: current capabilities and future opportunities.
AB  - The 2015/2016 El Nino was the first major climate variation when there were a
      range of satellite observations that simultaneously observed land, ocean and
      atmospheric properties associated with the carbon cycle. These data are beginning
      to provide new insights into the varied responses of land ecosystems to El Nino,
      but we are far from fully exploiting the information embodied by these data.
      Here, we briefly review the atmospheric and terrestrial satellite data that are
      available to study the carbon cycle. We also outline recommendations for future
      research, particularly the closer integration of satellite data with forest
      biometric datasets that provide detailed information about carbon dynamics on a
      range of timescales.This article is part of a discussion meeting issue 'The
      impact of the 2015/2016 El Nino on the terrestrial tropical carbon cycle:
      patterns, mechanisms and implications'.

PMID- 30297473
TI  - Widespread reduction in sun-induced fluorescence from the Amazon during the
      2015/2016 El Nino.
AB  - The tropical carbon balance dominates year-to-year variations in the CO2 exchange
      with the atmosphere through photosynthesis, respiration and fires. Because of its
      high correlation with gross primary productivity (GPP), observations of sun
      induced fluorescence (SIF) are of great interest. We developed a new remotely
      sensed SIF product with improved signal-to-noise in the tropics, and use it here
      to quantify the impact of the 2015/2016 El Nino Amazon drought. We find that SIF
      was strongly suppressed over areas with anomalously high temperatures and
      decreased levels of water in the soil. SIF went below its climatological range
      starting from the end of the 2015 dry season (October) and returned to normal
      levels by February 2016 when atmospheric conditions returned to normal, but well
      before the end of anomalously low precipitation that persisted through June 2016.
      Impacts were not uniform across the Amazon basin, with the eastern part
      experiencing much larger (10-15%) SIF reductions than the western part of the
      basin (2-5%). We estimate the integrated loss of GPP relative to eight previous
      years to be 0.34-0.48 PgC in the three-month period October-November-December
      2015.This article is part of a discussion meeting issue 'The impact of the
      2015/2016 El Nino on the terrestrial tropical carbon cycle: patterns, mechanisms
      and implications'.

PMID- 30297474
TI  - The impact of the 2015/2016 El Nino on global photosynthesis using satellite
      remote sensing.
AB  - The El Nino-Southern Oscillation exerts a large influence on global climate
      regimes and on the global carbon cycle. Although El Nino is known to be
      associated with a reduction of the global total land carbon sink, results based
      on prognostic models or measurements disagree over the relative contribution of
      photosynthesis to the reduced sink. Here, we provide an independent remote
      sensing-based analysis on the impact of the 2015-2016 El Nino on global
      photosynthesis using six global satellite-based photosynthesis products and a
      global solar-induced fluorescence (SIF) dataset. An ensemble of satellite-based
      photosynthesis products showed a negative anomaly of -0.7 +/- 1.2 PgC in 2015,
      but a slight positive anomaly of 0.05 +/- 0.89 PgC in 2016, which when combined
      with observations of the growth rate of atmospheric carbon dioxide concentrations
      suggests that the reduction of the land residual sink was likely dominated by
      photosynthesis in 2015 but by respiration in 2016. The six satellite-based
      products unanimously identified a major photosynthesis reduction of -1.1 +/- 0.52
      PgC from savannahs in 2015 and 2016, followed by a highly uncertain reduction of 
      0.22 +/- 0.98 PgC from rainforests. Vegetation in the Northern Hemisphere
      enhanced photosynthesis before and after the peak El Nino, especially in
      grasslands (0.33 +/- 0.13 PgC). The patterns of satellite-based photosynthesis
      ensemble mean were corroborated by SIF, except in rainforests and South America,
      where the anomalies of satellite-based photosynthesis products also diverged the
      most. We found the inter-model variation of photosynthesis estimates was strongly
      related to the discrepancy between moisture forcings for models. These results
      highlight the importance of considering multiple photosynthesis proxies when
      assessing responses to climatic anomalies.This article is part of a discussion
      meeting issue 'The impact of the 2015/2016 El Nino on the terrestrial tropical
      carbon cycle: patterns, mechanisms and implications'.

PMID- 30297476
TI  - Vulnerability of Amazonian forests to repeated droughts.
AB  - Extreme droughts have been recurrent in the Amazon over the past decades, causing
      socio-economic and environmental impacts. Here, we investigate the vulnerability
      of Amazonian forests, both undisturbed and human-modified, to repeated droughts.
      We defined vulnerability as a measure of (i) exposure, which is the degree to
      which these ecosystems were exposed to droughts, and (ii) its sensitivity,
      measured as the degree to which the drought has affected remote sensing-derived
      forest greenness. The exposure was calculated by assessing the meteorological
      drought, using the standardized precipitation index (SPI) and the maximum
      cumulative water deficit (MCWD), which is related to vegetation water stress,
      from 1981 to 2016. The sensitivity was assessed based on the enhanced vegetation
      index anomalies (AEVI), derived from the newly available Moderate Resolution
      Imaging Spectroradiometer (MODIS)/Multi-Angle Implementation of Atmospheric
      Correction algorithm (MAIAC) product, from 2003 to 2016, which is indicative of
      forest's photosynthetic capacity. We estimated that 46% of the Brazilian Amazon
      biome was under severe to extreme drought in 2015/2016 as measured by the SPI,
      compared with 16% and 8% for the 2009/2010 and 2004/2005 droughts, respectively.
      The most recent drought (2015/2016) affected the largest area since the drought
      of 1981. Droughts tend to increase the variance of the photosynthetic capacity of
      Amazonian forests as based on the minimum and maximum AEVI analysis. However, the
      area showing a reduction in photosynthetic capacity prevails in the signal,
      reaching more than 400 000 km2 of forests, four orders of magnitude larger than
      areas with AEVI enhancement. Moreover, the intensity of the negative AEVI
      steadily increased from 2005 to 2016. These results indicate that during the
      analysed period drought impacts were being exacerbated through time. Forests in
      the twenty-first century are becoming more vulnerable to droughts, with larger
      areas intensively and negatively responding to water shortage in the region.This
      article is part of a discussion meeting issue 'The impact of the 2015/2016 El
      Nino on the terrestrial tropical carbon cycle: patterns, mechanisms and
      implications'.

PMID- 30297475
TI  - ENSO Drives interannual variation of forest woody growth across the tropics.
AB  - Meteorological extreme events such as El Nino events are expected to affect
      tropical forest net primary production (NPP) and woody growth, but there has been
      no large-scale empirical validation of this expectation. We collected a large
      high-temporal resolution dataset (for 1-13 years depending upon location) of more
      than 172 000 stem growth measurements using dendrometer bands from across 14
      regions spanning Amazonia, Africa and Borneo in order to test how much month-to
      month variation in stand-level woody growth of adult tree stems (NPPstem) can be
      explained by seasonal variation and interannual meteorological anomalies. A key
      finding is that woody growth responds differently to meteorological variation
      between tropical forests with a dry season (where monthly rainfall is less than
      100 mm), and aseasonal wet forests lacking a consistent dry season. In seasonal
      tropical forests, a high degree of variation in woody growth can be predicted
      from seasonal variation in temperature, vapour pressure deficit, in addition to
      anomalies of soil water deficit and shortwave radiation. The variation of
      aseasonal wet forest woody growth is best predicted by the anomalies of vapour
      pressure deficit, water deficit and shortwave radiation. In total, we predict the
      total live woody production of the global tropical forest biome to be 2.16 Pg C
      yr-1, with an interannual range 1.96-2.26 Pg C yr-1 between 1996-2016, and with
      the sharpest declines during the strong El Nino events of 1997/8 and 2015/6.
      There is high geographical variation in hotspots of El Nino-associated impacts,
      with weak impacts in Africa, and strongly negative impacts in parts of Southeast
      Asia and extensive regions across central and eastern Amazonia. Overall, there is
      high correlation (r = -0.75) between the annual anomaly of tropical forest woody
      growth and the annual mean of the El Nino 3.4 index, driven mainly by strong
      correlations with anomalies of soil water deficit, vapour pressure deficit and
      shortwave radiation.This article is part of the discussion meeting issue 'The
      impact of the 2015/2016 El Nino on the terrestrial tropical carbon cycle:
      patterns, mechanisms and implications'.

PMID- 30297477
TI  - Drought-induced Amazonian wildfires instigate a decadal-scale disruption of
      forest carbon dynamics.
AB  - Drought-induced wildfires have increased in frequency and extent over the
      tropics. Yet, the long-term (greater than 10 years) responses of Amazonian
      lowland forests to fire disturbance are poorly known. To understand post-fire
      forest biomass dynamics, and to assess the time required for fire-affected
      forests to recover to pre-disturbance levels, we combined 16 single with 182
      multiple forest census into a unique large-scale and long-term dataset across the
      Brazilian Amazonia. We quantified biomass, mortality and wood productivity of
      burned plots along a chronosequence of up to 31 years post-fire and compared to
      surrounding unburned plots measured simultaneously. Stem mortality and growth
      were assessed among functional groups. At the plot level, we found that fire
      affected forests have biomass levels 24.8 +/- 6.9% below the biomass value of
      unburned control plots after 31 years. This lower biomass state results from the
      elevated levels of biomass loss through mortality, which is not sufficiently
      compensated for by wood productivity (incremental growth + recruitment). At the
      stem level, we found major changes in mortality and growth rates up to 11 years
      post-fire. The post-fire stem mortality rates exceeded unburned control plots by
      680% (i.e. greater than 40 cm diameter at breast height (DBH); 5-8 years since
      last fire) and 315% (i.e. greater than 0.7 g cm-3 wood density; 0.75-4 years
      since last fire). Our findings indicate that wildfires in humid tropical forests
      can significantly reduce forest biomass for decades by enhancing mortality rates
      of all trees, including large and high wood density trees, which store the
      largest amount of biomass in old-growth forests. This assessment of stem
      dynamics, therefore, demonstrates that wildfires slow down or stall the post-fire
      recovery of Amazonian forests.This article is part of a discussion meeting issue
      'The impact of the 2015/2016 El Nino on the terrestrial tropical carbon cycle:
      patterns, mechanisms and implications'.

PMID- 30297478
TI  - Changes in surface hydrology, soil moisture and gross primary production in the
      Amazon during the 2015/2016 El Nino.
AB  - The 2015/2016 El Nino event caused severe changes in precipitation across the
      tropics. This impacted surface hydrology, such as river run-off and soil moisture
      availability, thereby triggering reductions in gross primary production (GPP).
      Many biosphere models lack the detailed hydrological component required to
      accurately quantify anomalies in surface hydrology and GPP during droughts in
      tropical regions. Here, we take the novel approach of coupling the biosphere
      model SiBCASA with the advanced hydrological model PCR-GLOBWB to attempt such a
      quantification across the Amazon basin during the drought in 2015/2016. We
      calculate 30-40% reduced river discharge in the Amazon starting in October 2015,
      lagging behind the precipitation anomaly by approximately one month and in good
      agreement with river gauge observations. Soil moisture shows distinctly
      asymmetrical spatial anomalies with large reductions across the north-eastern
      part of the basin, which persisted into the following dry season. This added to
      drought stress in vegetation, already present owing to vapour pressure deficits
      at the leaf, resulting in a loss of GPP of 0.95 (0.69 to 1.20) PgC between
      October 2015 and March 2016 compared with the 2007-2014 average. Only 11% (10
      12%) of the reduction in GPP was found in the (wetter) north-western part of the
      basin, whereas the north-eastern and southern regions were affected more
      strongly, with 56% (54-56%) and 33% (31-33%) of the total, respectively.
      Uncertainty on this anomaly mostly reflects the unknown rooting depths of
      vegetation.This article is part of a discussion meeting issue 'The impact of the
      2015/2016 El Nino on the terrestrial tropical carbon cycle: patterns, mechanisms
      and implications'.

PMID- 30297479
TI  - ENSO effects on the transpiration of eastern Amazon trees.
AB  - Tree transpiration is important in the recycling of precipitation in the Amazon
      and might be negatively affected by El Nino-Southern Oscillation (ENSO)-induced
      droughts. To investigate the relative importance of soil moisture deficits versus
      increasing atmospheric demand (VPD) and determine if these drivers exert
      different controls over tree transpiration during the wet season versus the dry
      season (DS), we conducted sap flow measurements in a primary lowland tropical
      forest in eastern Amazon during the most extreme ENSO-induced drought (2015/2016)
      recorded in the Amazon. We also assessed whether trees occupying different canopy
      strata contribute equally to the overall stand transpiration (T stand). Canopy
      trees were the primary source of T stand However, subcanopy trees are still
      important as they transpired an amount similar to other biomes around the globe.
      Tree water use was higher during the DS, indicating that during extreme drought
      trees did not reduce transpiration in response to low soil moisture.
      Photosynthetically active radiation and VPD exerted an overriding effect on water
      use patterns relative to soil moisture during extreme drought, indicating that
      light and atmospheric constraints play a critical role in controlling ecosystem
      fluxes of water. Our study highlights the importance of canopy and subcanopy
      trees to the regional water balance and highlights the resilience to droughts
      that these trees show during an extreme ENSO event.This article is part of a
      discussion meeting issue 'The impact of the 2015/2016 El Nino on the terrestrial
      tropical carbon cycle: patterns, mechanisms and implications'.

PMID- 30297480
TI  - Interactive effects of tree size, crown exposure and logging on drought-induced
      mortality.
AB  - Large trees in the tropics are reportedly more vulnerable to droughts than their
      smaller neighbours. This pattern is of interest due to what it portends for
      forest structure, timber production, carbon sequestration and multiple other
      values given that intensified El Nino Southern Oscillation (ENSO) events are
      expected to increase the frequency and intensity of droughts in the Amazon
      region. What remains unclear is what characteristics of large trees render them
      especially vulnerable to drought-induced mortality and how this vulnerability
      changes with forest degradation. Using a large-scale, long-term silvicultural
      experiment in a transitional Amazonian forest in Bolivia, we disentangle the
      effects of stem diameter, tree height, crown exposure and logging-induced
      degradation on risks of drought-induced mortality during the 2004/2005 ENSO
      event. Overall, tree mortality increased in response to drought in both logged
      and unlogged plots. Tree height was a much stronger predictor of mortality than
      stem diameter. In unlogged plots, tree height but not crown exposure was
      positively associated with drought-induced mortality, whereas in logged plots,
      neither tree height nor crown exposure was associated with drought-induced
      mortality. Our results suggest that, at the scale of a site, hydraulic factors
      related to tree height, not air humidity, are a cause of elevated drought-induced
      mortality of large trees in unlogged plots.This article is part of a discussion
      meeting issue 'The impact of the 2015/2016 El Nino on the terrestrial tropical
      carbon cycle: patterns, mechanisms and implications'.

PMID- 30297482
TI  - Correction to 'State-of-the-art and future directions for extinction as a
      translational model for fear and anxiety'.

PMID- 30297483
TI  - GMC should hold conflicts of interest register for all doctors, says McCartney.

PMID- 30297481
TI  - Dry and hot: the hydraulic consequences of a climate change-type drought for
      Amazonian trees.
AB  - How plants respond physiologically to leaf warming and low water availability may
      determine how they will perform under future climate change. In 2015-2016, an
      unprecedented drought occurred across Amazonia with record-breaking high
      temperatures and low soil moisture, offering a unique opportunity to evaluate the
      performances of Amazonian trees to a severe climatic event. We quantified the
      responses of leaf water potential, sap velocity, whole-tree hydraulic conductance
      (K wt), turgor loss and xylem embolism, during and after the 2015-2016 El Nino
      for five canopy-tree species. Leaf/xylem safety margins (SMs), sap velocity and K
      wt showed a sharp drop during warm periods. SMs were negatively correlated with
      vapour pressure deficit, but had no significant relationship with soil water
      storage. Based on our calculations of canopy stomatal and xylem resistances, the
      decrease in sap velocity and K wt was due to a combination of xylem cavitation
      and stomatal closure. Our results suggest that warm droughts greatly amplify the
      degree of trees' physiological stress and can lead to mortality. Given the
      extreme nature of the 2015-2016 El Nino and that temperatures are predicted to
      increase, this work can serve as a case study of the possible impact climate
      warming can have on tropical trees.This article is part of a discussion meeting
      issue 'The impact of the 2015/2016 El Nino on the terrestrial tropical carbon
      cycle: patterns, mechanisms and implications'.

PMID- 30297484
TI  - RCC in cross ectopic kidney: a challenging diagnosis and management.

PMID- 30297485
TI  - Strangulated urethral prolapse in a postmenopausal woman presenting as acute
      urinary retention.

PMID- 30297486
TI  - Pulmonary capillary haemangiomatosis causing pulmonary arterial hypertension: a
      clinician's conundrum.

PMID- 30297487
TI  - Case of solitary plasmacytoma of tibia.

PMID- 30297488
TI  - Dermatomyositis with anti-TIF1-gamma antibodies.

PMID- 30297489
TI  - Myasthenia gravis crisis coinciding with asthma exacerbation in a patient with
      recent heroin use: three causes of acute hypercarbic respiratory failure.
AB  - A 57-year-old woman with a history of asthma, hypertension and substance abuse
      disorder was admitted to the medical intensive care unit with hypercapnic
      respiratory failure. After the history was obtained, patient admitted heroin use
      earlier that day. The initial physical examination revealed right eye ptosis,
      diplopia, fatigability of neck flexion and extension. She also presented with
      wheezing and a prolonged expiratory phase. Pupils were 4 mm, with sluggish
      response to light bilaterally. CT chest with contrast showed a large mediastinal
      mass. Three different processes coexisted in this patient: simultaneous
      occurrence of a myasthenia gravis crisis, asthma exacerbation and a component of
      heroin use. This case highlights a series of overlapping clinical features that
      could lead to potential confounding and misdiagnosis. Respiratory symptoms
      improved after initial treatment for asthma exacerbation, but ptosis, diplopia
      and fatigability of neck muscles persisted.

PMID- 30297490
TI  - Uncommon manifestation of leptospirosis: a diagnostic challenge.
AB  - Leptospirosis is a zoonotic disease commonly affecting the tropical countries. It
      may have protean clinical manifestations including hepatorenal dysfunction,
      myocarditis, pulmonary haemorrhage, meningitis, optic neuritis and
      rhabdomyolysis. Neurological manifestation of leptospirosis without the classical
      hepatorenal dysfunction is a rare entity. This complication of leptospirosis can
      present with diverse central and peripheral neurological presentations. The
      overlapping clinical manifestations with many common tropical pathogens often
      pose diagnostic dilemma and delay in definitive therapy may lead to adverse
      clinical consequences. We report a case of a 19-year-old man with no prior
      comorbidities presenting with high-grade fever and altered sensorium. He was
      diagnosed to be a probable case of leptospirosis, based on all available test
      results and by fulfilment of parameters under modified Faine's criteria. The
      patient was successfully managed and discharged in stable condition.

PMID- 30297492
TI  - Woman with lower back pain, SIADH and a twist of Lyme.
AB  - A 62-year-old woman was admitted with a 3-week history of atraumatic bilateral
      lower back pain, progressive ascending flaccid paralysis, hyponatraemia and
      constipation. She was otherwise in good health with only a recent diagnosis of
      acute gastroenteritis that preceded her presenting symptoms. Her initial
      laboratory evaluation was consistent with Syndrome of Inappropriate Antidiuretic
      Hormone (SIADH) but was otherwise unremarkable. MRI of the spine revealed
      bilateral diffuse nerve root enhancement from at least C6 to the conus level,
      suggesting an inflammatory process. Lumbar puncture demonstrated high protein
      (629 mg/dL) with marked pleocytosis (363 cells/mcL) incompatible with
      albuminocytological dissociation typically seen in Guillain-Barre syndrome. A
      thorough diagnostic evaluation was undertaken to explore potential infectious,
      malignant and autoimmune conditions. Lyme disease serology (ELISA and Western
      Blot, IgM and IgG) was positive leading to a final diagnosis of lymphocytic
      meningoradiculitis or Bannwarth syndrome.

PMID- 30297491
TI  - Solitary vallecular neurofibroma presenting with respiratory obstruction: an
      unusual presentation.
AB  - An occurrence of vallecular neurofibroma with airway obstruction is extremely
      rare and to the best of our knowledge, no case report has been documented in the
      literature to date. Although microlaryngeal surgery with cold knife excision is
      the standard surgical procedure offered to patients of vallecular lesions, it can
      be successfully managed with the help of endoscopic coblation as later can
      provide a bloodless surgical field preventing the unmet need for the tracheostomy
      and reducing the postoperative morbidities.

PMID- 30297493
TI  - Pericardial sarcoma.
AB  - Pericardial sarcomas are extremely rare aggressive neoplasms. Non-specific
      symptoms and incidental discovery are usually the rule. Multimodality imaging is
      extremely important for diagnosis and tissue characterisation of all cardiac
      masses. Despite treatment, pericardial sarcomas are considered extremely fatal.
      We encountered a 27-year-old female patient who presented to our facility with
      progressive dyspnoea. On examination, clinical signs of cardiac tamponade were
      appreciated, transthoracic echocardiography revealed a tamponading pericardial
      effusion and a large heterogeneous pericardial mass. Pericardiocentesis revealed
      haemorrhagic fluid. Subsequently, CT revealed a pericardial mass compressing the
      right atrium. Excision biopsy showed a well-circumscribed mass, and cut sections
      showed friable grey-white tissue with areas of haemorrhage and necrosis.
      Pathological examination confirmed the diagnosis of high-grade undifferentiated
      sarcoma of the pericardium. The patient was started on adjuvant chemotherapy and
      radiotherapy. Follow-up after 1 year showed no relapse.

PMID- 30297494
TI  - Isoniazid-induced pure red cell aplasia.
AB  - The pure red cell aplasia (PRCA) is an uncommon side effect of isoniazid. We
      describe a 28-year-old man who developed a severe anaemia caused by PRCA. The
      patient received antituberculous therapy including isoniazid for his pulmonary
      tuberculosis. On discontinuation of isoniazid, the anaemia recovered promptly.
      PRCA should be considered in case of unexplained anaemia during isoniazid
      treatment.

PMID- 30297495
TI  - Large mesenteric lymphangioma in an adult patient: an unusual presentation of a
      rare disease.
AB  - Lymphangiomas are most commonly described as a small painless mass in the neck or
      a vesicular rash in an infant patient. Ninety per cent of cases are diagnosed
      before the age of 2. Treatment usually involves surgical resection. Intra
      abdominal lymphangiomas and mesenteric lymphangiomas, as described in our case
      report, represent a rare pathology. The exact prevalence of this condition is
      unclear but it has been suggested in the literature that there have been as few
      as 820 cases since the 16th century. The clinical presentation is usually
      subacute and diagnosis made incidentally during a workup of chronic
      gastrointestinal symptoms. Acute abdominal symptoms, as in our case presentation,
      are unusual but may be explained by the mass effect of a large intra-abdominal
      lesion. Cross-sectional imaging is key in preoperative workup and operative
      planning. Complete surgical resection is recommended and curative in the majority
      of cases with a low risk of local recurrence.

PMID- 30297497
TI  - Cutis marmorata telangiectatica congenita with skin ulceration: a rare benign
      skin vascular malformation.

PMID- 30297496
TI  - Rare case of adult pancreatic haemangioma and literature review.
AB  - Pancreatic haemangiomas are benign vascular tumours very rare in adults. Twenty
      two cases are described in the literature. The symptoms are non-specific, and
      therefore rarely clinically suspected, and the vast majority are incidental
      findings in imaging tests such as ultrasound, CT, angiography or MRI. They appear
      on CT as a cystic lesion with contrast enhancement in the arterial phase. We
      present the case of a 36-year-old male patient with no history of disease,
      referred with lumbar pain and suspected renal calculus after tomography showing
      hypervascular enhancement in the pancreatic body and infiltrative lesion
      (possible neuroendocrine neoplasia) on MRI and biliopancreatic echoendoscopy. He
      was submitted to laparotomy with subtotal pancreatectomy and splenectomy and
      satisfactory evolution.

PMID- 30297498
TI  - Tobacco smoke and environmental injustice.

PMID- 30297499
TI  - Acetaminophen and Febrile Seizure Recurrences During the Same Fever Episode.
AB  - OBJECTIVES: To confirm the safety of using acetaminophen for febrile seizures
      (FSs) and to assess its efficacy in preventing FS recurrence during the same
      fever episode. METHODS: In this single-center, prospective, open, randomized
      controlled study, we included children and infants (age range: 6-60 months) with
      FSs who visited our hospital between May 1, 2015, and April 30, 2017. The
      effectiveness of acetaminophen was examined by comparing the recurrence rates of
      patients in whom rectal acetaminophen (10 mg/kg) was administered every 6 hours
      until 24 hours after the first convulsion (if the fever remained >38.0 degrees C)
      to the rates of patients in whom no antipyretics were administered. No placebo
      was administered to controls. The primary outcome measure was FS recurrence
      during the same fever episode. RESULTS: We evaluated 423 patients; of these, 219
      were in the rectal acetaminophen group, and 204 were in the no antipyretics
      group. In the univariate analysis, the FS recurrence rate was significantly lower
      in the rectal acetaminophen group (9.1%) than in the no antipyretics group
      (23.5%; P < .001). Among the variables in the final multiple logistic regression
      analysis, rectal acetaminophen use was the largest contributor to the prevention
      of FS recurrence during the same fever episode (odds ratio: 5.6; 95% confidence
      interval: 2.3-13.3). CONCLUSIONS: Acetaminophen is a safe antipyretic against FSs
      and has the potential to prevent FS recurrence during the same fever episode.

PMID- 30297500
TI  - Effectiveness of a Hand Hygiene Program at Child Care Centers: A Cluster
      Randomized Trial.
AB  - OBJECTIVES: Respiratory infections (RIs) are an important cause of morbidity and
      excessive antibiotic prescriptions in children attending day care centers (DCCs).
      We aimed to assess the effectiveness of an educational and hand hygiene program
      in DCCs and homes in reducing RI incidence and antibiotic prescriptions in
      children. METHODS: A cluster, randomized, controlled, and open study of 911
      children aged 0 to 3 years attending 24 DCCs in Almeria (Spain) with an 8-month
      follow-up. Two intervention groups of DCC families performed educational and hand
      hygiene measures, 1 with soap and water (SWG; n = 274), another with hand
      sanitizer (HSG; n = 339), and the control group (CG; n = 298) followed usual hand
      washing procedures. RI episode rates were compared through multilevel Poisson
      regression models. The percentage of days missed were compared with Poisson exact
      tests. RESULTS: There were 5211 RI episodes registered. Children in the HSG had
      less risk of RI episodes (incidence rate ratio [IRR]: 0.77; 95% confidence
      interval [CI]: 0.68-0.88) and antibiotic prescriptions (IRR: 0.69; 95% CI: 0.57
      0.84) compared with the those in the CG. Children in the SWG had a higher risk of
      RI episodes (IRR: 1.21; 95% CI: 1.06-1.39) and antibiotic prescriptions (IRR:
      1.31; 95% CI: 1.08-1.56) than those in the HSG. Pupils missed 5186 DCC days
      because of RIs, and the percentage of days absent was significantly lower in the
      HSG compared with the CG (P < .001) and the SWG (P < .001). CONCLUSIONS: Hand
      hygiene programs that include hand sanitizer and educational measures for DCC
      staff, children, and parents, reduce absent days, RIs, and antibiotic
      prescriptions for these infections in children at DCCs.

PMID- 30297501
TI  - What's happening in Neurology (r) Clinical Practice.

PMID- 30297503
TI  - Unusual presentation of an Adie-like pupil: Cat's eye pupil.

PMID- 30297502
TI  - CNS disease-related protein variants as blood-based biomarkers in traumatic brain
      injury.
AB  - OBJECTIVE: To utilize a panel of 11 single chain variable fragments (scFvs) that
      selectively bind disease-related variants of TAR DNA-binding protein (TDP)-43,
      beta-amyloid, tau, and alpha-synuclein to assess damage following traumatic brain
      injury (TBI), and determine if the presence of protein variants could account for
      the increased risk of various neurodegenerative diseases following TBI. METHODS:
      We utilized the panel of 11 scFvs in a sensitive ELISA format to analyze sera
      from 43 older veterans, 25 who had experienced at least 1 TBI incident during
      their lifetime (~29.4 years after TBI), and 18 controls who did not incur TBI, in
      a cross-sectional study. RESULTS: Each of the 11 scFvs individually could
      significantly distinguish between TBI and control samples, though they did not
      detect each TBI sample. Comparing the levels of all 11 variants, all 25 TBI cases
      displayed higher reactivity compared to the controls and receiver operating
      characteristic analysis revealed 100% sensitivity and specificity. Higher total
      protein variants levels correlated with TBI severity and with loss of
      consciousness. Oligomeric tau levels distinguished between single and multiple
      TBI incidents. While all TBI cases were readily selected with the panel, the
      binding pattern varied from patient to patient, suggesting subgroups that are at
      increased risk for different neurodegenerative diseases. CONCLUSION: The panel of
      protein variants-specific scFvs can be used to identify blood-based biomarkers
      indicative of TBI even 20 years or more after the initial TBI. Being able to
      identify subgroups of biomarker profiles allows for the possibility of
      individually targeted treatments.

PMID- 30297504
TI  - Pearls & Oy-sters: Enhancing vigilance for detection of cerebral air embolism:
      From syncope to death.

PMID- 30297505
TI  - Editors' note: Behavioral interventions as a treatment for epilepsy: A
      multicenter randomized controlled trial.

PMID- 30297506
TI  - Reader response: Behavioral interventions as a treatment for epilepsy: A
      multicenter randomized controlled trial.

PMID- 30297508
TI  - Editors' note: The nature of postural tremor in Parkinson disease.

PMID- 30297507
TI  - Author response: Behavioral interventions as a treatment for epilepsy: A
      multicenter randomized controlled trial.

PMID- 30297509
TI  - Reader response: The nature of postural tremor in Parkinson disease.

PMID- 30297510
TI  - Author response: The nature of postural tremor in Parkinson disease.

PMID- 30297511
TI  - Teaching NeuroImages: Morning glory disc anomaly.

PMID- 30297512
TI  - Teaching NeuroImages: Lyme disease presenting as Bannwarth syndrome.

PMID- 30297513
TI  - Do apes smell like humans? The role of skin bacteria and volatiles of primates in
      mosquito host selection.
AB  - Anthropophilic mosquitoes are effective vectors of human disease because of their
      biting preferences. To find their host, these mosquitoes are guided by human
      odours, primarily produced by human skin bacteria. By analysing the skin
      bacterial and skin volatile profiles of humans, bonobos, chimpanzees, gorillas,
      lemurs and cows, we investigated whether primates that are more closely related
      to humans have a skin bacterial community and odour profile that is similar to
      that of humans. We then investigated whether this affected discrimination between
      humans and closely related primates by anthropophilic and zoophilic mosquitoes
      that search for hosts. Humans had a lower skin bacterial diversity than the other
      animals and their skin bacterial composition was more similar to that in other
      primates than it was to the skin bacteria of cows. Like the skin bacterial
      profiles, the volatile profiles of the animal groups were clearly different from
      each other. The volatile profiles of cows and lemurs were more closely related to
      the human profiles than expected. Human volatiles were indeed preferred above cow
      volatiles by anthropophilic mosquitoes and no preference was observed when tested
      against non-human primate odour, except for bonobo volatiles, which were
      preferred over human volatiles. Unravelling the differences between mosquito
      hosts and their effect on host selection is important for a better understanding
      of cross-species transmission of vector-borne diseases.

PMID- 30297514
TI  - Endotoxin rapidly desensitizes the gonads to kisspeptin-induced luteinizing
      hormone release in male Siberian hamsters (Phodopus sungorus).
AB  - Activation of the immune system induces rapid reductions in hypothalamic
      pituitary-gonadal (HPG) axis activity, which in turn decreases secretion of sex
      steroids. This response is likely adaptive for survival by temporarily inhibiting
      reproduction to conserve energy; however, the physiological mechanisms
      controlling this response remain unclear. The neuropeptide kisspeptin is a
      candidate to mediate the decrease in sex hormones seen during sickness through
      its key regulation of the HPG axis. In this study, the effects of acute immune
      activation on the response to kisspeptin were assessed in male Siberian hamsters
      (Phodopus sungorus). Specifically, an immune response was induced in animals by a
      single treatment of lipopolysaccharide (LPS), and reproductive hormone
      concentrations were determined in response to subsequent injections of exogenous
      kisspeptin. Saline-treated controls showed a robust increase in circulating
      testosterone in response to kisspeptin; however, this response was blocked in LPS
      treated animals. Circulating luteinizing hormone (LH) levels were elevated in
      response to kisspeptin in both LPS- and saline-treated groups and, thus, were
      unaffected by LPS treatment, suggesting gonad-level inhibition of testosterone
      release despite central HPG activation. In addition, blockade of glucocorticoid
      receptors by mifepristone did not attenuate the LPS-induced inhibition of
      testosterone release, suggesting that circulating glucocorticoids do not mediate
      this phenomenon. Collectively, these findings reveal that acute endotoxin
      exposure rapidly renders the gonads less sensitive to HPG stimulation, thus
      effectively inhibiting sex hormone release. More broadly, these results shed
      light on the effects of immune activation on the HPG axis and help elucidate the
      mechanisms controlling energy allocation and reproduction.

PMID- 30297515
TI  - Relationship between circulating inflammation proteins and lung cancer diagnosis
      in the National Lung Screening Trial.
AB  - BACKGROUND: Previously, we observed a strong relationship between circulating
      serum inflammation proteins in relation to lung cancer diagnosis and risk, both
      in case-control and prospective cohorts. Low dose CT (LDCT) screening has a high
      prevalence of false positive nodules, thus companion non-invasive biomarkers that
      can distinguish between benign and malignant nodules could have clinical utility
      and positive impact on patient outcomes. METHODS: We conducted a nested case
      control study within the National Lung Screening Trial (NLST). Concentrations of
      30 inflammation proteins were measured on plasma samples of 262 cases and 528
      controls using a highly sensitive and analytically validated
      electrochemiluminescence V-PLEX immunoassay. RESULTS: Comparing the 4th quartile
      with 1st quartile, we found increased IFN-gamma and IL-12/IL-23p40 associated
      with increased odds of a lung cancer diagnosis (OR 1.89, 95% C.I. 1.16-3.09; OR
      2.49, 95% C.I. 1.46-4.23, respectively). Confirming our previous observations, we
      also detected a relationship between increased IL-6, IL-8 and CRP with lung
      cancer diagnosis. These relationships were significant after adjustment for age,
      gender, race, smoking, BMI, family history of lung cancer and previous diagnoses
      of inflammatory conditions. However, none of these proteins could distinguish
      between a benign and malignant lung nodule (IL-6: OR 1.25, 95% C.I. 0.59-2.64; IL
      8: OR 1.40, 95% C.I. 0.70-2.81; CRP: OR 0.98, 95% C.I. 0.45-2.12). CONCLUSIONS:
      We have discovered new associations for IFN-gamma and IL-12/IL-23p40 with lung
      cancer but have no evidence that these proteins can distinguish between benign
      and malignant lung nodules. IMPACT: Circulating inflammation proteins are
      unlikely to have utility as companion LDCT biomarkers.

PMID- 30297516
TI  - Exposure to trace elements and risk of skin cancer: A systematic review of
      epidemiologic studies.
AB  - Exposure to environmental trace elements has been studied in relation to many
      cancers. However, an association between exposure to trace elements and skin
      cancer remains less understood. Therefore, we conducted a systematic review of
      published epidemiologic literature examining the association between exposure to
      trace elements, and risk of melanoma and keratinocyte carcinoma in humans. We
      identified epidemiologic studies investigating exposure to arsenic, cadmium,
      chromium, copper, iron, selenium, and zinc and risk of skin cancer in humans.
      Among the minerals, arsenic, selenium, and zinc had more than 5 studies
      available. Exposure to arsenic was associated with increased risk of keratinocyte
      carcinoma, while too few studies existed on melanoma to draw conclusions.
      Exposure to selenium was associated with possible increased risk of keratinocyte
      carcinoma. Studies of zinc and skin cancer were case-control in design and were
      found to have inconsistent associations. The data on the association between
      cadmium, chromium, copper, and iron and risk of skin cancer remain too sparse to
      draw any conclusions. In summary, epidemiologic studies on exposure to trace
      elements and cutaneous malignancies are limited. Studies with larger sample sizes
      and prospective designs are warranted to improve our knowledge of trace elements
      and skin cancer.

PMID- 30297517
TI  - Perivascular enhancement in anti-MOG antibody demyelinating disease of the CNS.

PMID- 30297518
TI  - Elevated YKL-40 and low sAPPbeta:YKL-40 ratio in antemortem cerebrospinal fluid
      of patients with pathologically confirmed FTLD.
AB  - OBJECTIVES: The combination of high YKL-40 (a glial inflammatory marker) and low
      sAPPbeta (a soluble beta fragment of amyloid precursor protein) in cerebrospinal
      fluid (CSF) has been associated with frontotemporal lobar degeneration (FTLD) in
      clinical series. We investigate these biomarkers in a neuropathologically
      confirmed cohort of patients with FTLD. METHODS: CSF samples were selected from
      the Penn FTD Center (University of Pennsylvania). Participants were followed to
      autopsy and had a neuropathological diagnosis of FTLD-Tau (n=24), transactive
      response DNA-binding protein with 43 kDa (FTLD-TDP) (n=25) or Alzheimer's disease
      (AD, n=97). We compared levels of YKL-40 and sAPPbeta between groups and with
      cognitively normal controls (n=77), and assessed their diagnostic utility using
      receiver operating characteristic curves. We also investigated the effect of AD
      copathology and the correlation between these CSF markers and tau burden at
      autopsy. RESULTS: Both FTLD groups had lower levels of sAPPbeta, higher levels of
      YKL-40 and lower sAPPbeta:YKL-40 ratio in CSF compared with controls. The group
      of pure FTLD-Tau (without AD copathology) showed higher levels of YKL-40 than AD
      and than pure FTLD-TDP. YKL-40 levels correlated with pathological tau burden.
      The sAPPbeta:YKL-40 ratio had an area under the curve (AUC) of 0.91 (95% CI 0.86
      to 0.96) to distinguish subjects with FTLD from controls, but lower values to
      distinguish FTLD from AD (AUC 0.70; 95%  CI 0.61 to 0.79) and to discriminate
      FTLD-Tau from FTLD-TDP (AUC 0.67; 95%  CI 0.51 to 0.82). CONCLUSIONS: Our study
      provides pathological confirmation that the combination of low sAPPbeta and high
      YKL-40 in CSF is associated with FTLD. These biomarkers could be useful in
      particular clinical settings when FTLD is suspected.

PMID- 30297519
TI  - Cognitive decline in Parkinson's disease: the impact of the motor phenotype on
      cognition.
AB  - OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative
      disorder and is further associated with progressive cognitive decline. In respect
      to motor phenotype, there is some evidence that akinetic-rigid PD is associated
      with a faster rate of cognitive decline in general and a greater risk of
      developing dementia.The objective of this study was to examine cognitive profiles
      among patients with PD by motor phenotypes and its relation to cognitive
      function. METHODS: Demographic, clinical and neuropsychological cross-sectional
      baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort
      study of 538 patients with PD were analysed, stratified by motor phenotype and
      cognitive syndrome. Analyses were performed for all patients and for each
      diagnostic group separately, controlling for age, gender, education and disease
      duration. RESULTS: Compared with the tremor-dominant phenotype, akinetic-rigid
      patients performed worse in executive functions such as working memory (Wechsler
      Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043),
      card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and
      visuospatial abilities (Leistungsprufungssystem test 9; p=0.006). Akinetic-rigid
      neuropsychological test scores for the executive and attentive domain correlated
      negatively with non-tremor motor scores. Covariate-adjusted binary logistic
      regression analyses showed significant odds for PD-mild cognitive impairment for
      not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD
      (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as
      compared with tremor-dominant phenotype (OR=8.314). CONCLUSION: The three motor
      phenotypes of PD differ in cognitive performance, showing that cognitive deficits
      seem to be less severe in tremor-dominant PD. While these data are cross
      sectional, longitudinal data are needed to shed more light on these differential
      findings.

PMID- 30297521
TI  - The reunification of amyotrophic lateral sclerosis.

PMID- 30297522
TI  - Atypical chronic inflammatory demyelinating polyneuropathies.

PMID- 30297520
TI  - Atypical CIDP: diagnostic criteria, progression and treatment response. Data from
      the Italian CIDP Database.
AB  - OBJECTIVES: A few variants of chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP) have been described, but their frequency and
      evolution to typical CIDP remain unclear. To determine the frequency and
      characteristics of the CIDP variants, their possible evolution to typical CIDP,
      and treatment response. METHODS: We applied a set of diagnostic criteria to 460
      patients included in a database of Italian patients with CIDP. Clinical
      characteristics and treatment response were reviewed for each patient. The Kaplan
      Meier curve was used to estimate the progression rate from atypical to typical
      CIDP. RESULTS: At the time of inclusion, 376 (82%) patients had a diagnosis of
      typical CIDP while 84 (18%) had atypical CIDP, including 34 (7%) with distal
      acquired demyelinating symmetric neuropathy (DADS), 17 (4%) with purely motor, 17
      (4%) with Lewis-Sumner syndrome (LSS) and 16 (3.5%) with purely sensory CIDP.
      Based on retrospective review of the symptoms and signs present at onset and for
      at least 1 year, 180 (39%) patients had an initial diagnosis compatible with
      atypical CIDP that in 96 (53%) patients evolved to typical CIDP. Mean disease
      duration was longer in patients evolving to typical CIDP than in those not
      evolving (p=0.0016). Patients with DADS and LSS had a less frequent response to
      immunoglobulin than those with typical CIDP, while patients with purely motor and
      sensory CIDP had a similar treatment response. CONCLUSIONS: The proportion of
      patients with atypical CIDP varies during the disease course. DADS and LSS have a
      less frequent response to intravenous immunoglobulin compared with typical CIDP,
      raising the possibility of a different underlying pathogenetic mechanism.

PMID- 30297523
TI  - Tamm-Horsfall protein protects the urinary tract against Candida albicans.
AB  - Urinary tract infections (UTIs) caused by the human fungal pathogen Candida
      albicans and related species are prevalent in hospitalized patients, especially
      those on antibiotic therapy, with indwelling catheters, or with predisposing
      conditions such as diabetes or immunodeficiency. Understanding of key host
      defenses against Candida UTI are critical for developing effective treatment
      strategies. Tamm-Horsfall glycoprotein (THP) is the most abundant urine protein
      with multiple roles in renal physiology and bladder protection. THP protects
      against bacterial UTI by blocking bacterial adherence to the bladder epithelium,
      but its role in defense against fungal pathogens is not yet described. Here, we
      demonstrate that THP restricts colonization of the urinary tract by C. albicans
      THP binds to C. albicans hyphae, but not the yeast form, in a manner dependent on
      fungal expression of the Als3 adhesion glycoprotein. THP directly blocks C.
      albicans adherence to bladder epithelial cells in vitro and THP-deficient mice
      display increased fungal burden in a C. albicans UTI model. This work outlines a
      previously unknown role for THP as an essential component for host immune defense
      against fungal urinary tract infection.

PMID- 30297525
TI  - A non-fimbrial adhesin of Aggregatibacter actinomycetemcomitans mediates biofilm
      biogenesis.
AB  - Periodontitis is an inflammatory disease caused by polymicrobial biofilms. The
      periodontal pathogen Aggregatibacter actinomycetemcomitans displays two
      proteinaceous surface structures, the fimbriae and the non-fimbrial extracellular
      matrix binding protein A (EmaA), as observed by electron microscopy. Fimbriae
      participate in biofilm biogenesis and the EmaA adhesins mediate collagen binding.
      However, in the absence of fimbriae, A. actinomycetemcomitans still retains the
      potential to form robust biofilms, suggesting other surface macromolecules
      participate in biofilm development. Here, isogenic mutant strains lacking EmaA
      structures, but still expressing fimbriae, were observed to have reduced biofilm
      potential. In strains lacking both EmaA and fimbriae, biofilm mass was reduced by
      80%. EmaA enhanced biofilm formation in different strains, independent of the
      fimbriation state or serotype. Confocal microscopy revealed differences in cell
      density within microcolonies between the EmaA positive and mutant strains. EmaA
      mediated biofilm formation was found to be independent of the glycosylation state
      and the precise 3-D conformation of the protein, and thus this function is
      uncorrelated with collagen binding activity. The data suggests that EmaA is a
      multifunctional adhesin that utilizes different mechanisms to enhance bacterial
      binding to collagen and to enhance biofilm formation, both of which are important
      for A. actinomycetemcomitans colonization and subsequent infection.

PMID- 30297524
TI  - NanI Sialidase Is an Important Contributor to Clostridium perfringens Type F
      Strain F4969 Intestinal Colonization in Mice.
AB  - Clostridium perfringens type F (formerly enterotoxigenic C. perfringens type A)
      strains produce an enterotoxin (CPE) to cause acute cases of food poisoning and
      chronic nonfoodborne human gastrointestinal diseases (NFD), e.g., antibiotic
      associated diarrhea (AAD). NFD strains also produce NanI sialidase, an
      extracellular enzyme that releases sialic acids from sialyated host
      macromolecules. Recent in vitro studies suggested that NanI may contribute to NFD
      strain intestinal colonization by enhancing the adherence of such strains to
      intestinal cells and promoting their bacterial growth using generated sialic acid
      as an energy source. The current study tested this hypothesis by developing a
      mouse intestinal colonization model involving clindamycin pretreatment to produce
      conditions mimicking those during AAD. In this model, the type F NFD strain F4969
      persisted for at least 4 days in the small intestine, cecum, and colon. When
      clindamycin-pretreated mice were challenged by oral gavage with equivalent
      numbers of F4969 bacteria or its isogenic nanI null mutant, significantly lower
      numbers of the nanI mutant were recovered from all intestinal segments, and it
      was completely cleared from the small intestine by day 4. Complementation of the
      mutant to restore NanI production also promoted colonization. When the same nanI
      null mutant strain was coinoculated into the mouse model together with a nanI
      producing strain, the numbers of this mutant were restored to wild-type F4969
      levels in all intestinal segments. This result suggests that sialidases produced
      by other bacteria might also provide some support for C. perfringens intestinal
      colonization. Collectively, these in vivo findings identify NanI to be the first
      known significant contributor to chronic intestinal colonization by NFD strains.

PMID- 30297526
TI  - Atg5 Supports R. australis Infection in Macrophages in vitro and in vivo.
AB  - Rickettsiae can cause life-threatening infections in humans. Macrophages are one
      of the initial targets for rickettsiae after inoculation by ticks. However, it
      remains poorly understood how rickettsiae remain free in macrophages prior to
      establishing their infection in microvascular endothelial cells. Here, we
      demonstrated that the concentration of Rickettsia australis was significantly
      greater in infected tissues of Atg5flox/flox mice compared to the counterparts of
      Atg5flox/flox Lyz-Cre mice, in association with a reduced level of IL-1beta in
      serum. The greater concentration of R. australis in Atg5 flox/flox bone marrow
      derived macrophages (BMMs) compared to Atg5 flox/flox Lyz-Cre BMMs in vitro was
      abolished by exogenous treatment with recombinant IL-1beta. Rickettsia australis
      induced significantly increased levels of LC3-II and LC3 puncta in Atg5-competent
      BMMs, but not in Atg5- deficient BMMs, while no p62 turnover was observed.
      Further analysis found that the co-localization of LC3 with a small portion of R.
      australis and Rickettsia-containing double-membrane-bound vacuoles in BMMs of B6
      mice. Moreover, treatment with rapamycin significantly increased the
      concentrations of R. australis in B6 BMMs compared to the untreated controls.
      Taken together, our results demonstrated that Atg5 favors R. australis infection
      in mouse macrophages in association with a suppressed production level of IL
      1beta but not active autophagy flux. These data highlight the contribution of
      Atg5 in macrophages to the pathogenesis of rickettsial diseases.

PMID- 30297527
TI  - Acinetobacter baumannii OxyR regulates the transcriptional response to hydrogen
      peroxide.
AB  - Acinetobacter baumannii is a Gram-negative opportunistic pathogen that causes
      diverse infections, including pneumonia, bacteremia, and wound infections. Due to
      multiple intrinsic and acquired antimicrobial-resistance mechanisms, A. baumannii
      isolates are commonly multi-drug resistant and infections are notoriously
      difficult to treat. The World Health Organization recently highlighted carbapenem
      resistant A. baumannii as a 'critical priority' for the development of new
      antimicrobials because of the risk to human health posed by this organism.
      Therefore, it is important to discover mechanisms used by A. baumannii to survive
      stresses encountered during infection in order to identify new drug targets. In
      this study, we identified hydrogen peroxide (H2O2) as a stressor produced in the
      lung during A. baumannii infection using in vivo imaging and defined OxyR as a
      transcriptional regulator of the H2O2 stress response. Upon exposure to H2O2, A.
      baumannii differentially transcribes several hundred genes. However,
      transcriptional upregulation of genes predicted to detoxify hydrogen peroxide is
      abolished in A. baumannii genetically inactivated for the transcriptional
      regulator oxyR. Moreover, inactivation of oxyR in both antimicrobial-susceptible
      and multi-drug-resistant A. baumannii strains impairs growth in the presence of
      H2O2 OxyR is a direct regulator of katE and ahpF1, which encode the major H2O2
      degrading enzymes in A. baumannii, as confirmed through measurement of promoter
      binding by recombinant OxyR in electromobility shift assays. Finally, an oxyR
      mutant is less fit than wild-type A. baumannii during infection of the murine
      lung. This work reveals a mechanism used by this important human pathogen to
      survive H2O2 stress encountered during infection.

PMID- 30297528
TI  - How to improve the assessment of the impact of occupational diseases at a
      national level? The Netherlands as an example.
AB  - OBJECTIVE: To explore the impact of occupational diseases (ODs) through
      estimations of population attributable fractions (PAFs) in a national context.
      METHODS: PAFs were calculated for eight prevalent ODs using existing data on the
      prevalence of exposure to risk factors at work and the strength of their
      association with diseases based on systematic reviews. Six systematic reviews
      with meta-analyses and two overview papers were selected. All addressed the
      relationship between occupational exposure to work-related risk factors for these
      eight prevalent ODs. Prevalence figures for exposure to work-related risk factors
      were retrieved from the Dutch National Working Conditions Survey (NWCS) based on
      self-reports by approximately 40 000 workers. The specific risk factors retrieved
      from the reviews were matched with the available and dichotomised self-reported
      exposure items from the NWCS by two authors. RESULTS: The eight frequently
      reported ODs among the Dutch working population revealed PAFs varying between 3%
      and 25%. Lateral epicondylitis and distress/burnout had the highest attributable
      fractions, with percentages of 25% and 18%, respectively. For knee osteoarthritis
      (13%), shoulder soft tissue disorders (10%) and non-specific low back pain (10%)
      approximately 1 in 10 cases were attributable to work. PAFs for irritant contact
      dermatitis, noise-induced hearing loss and chronic obstructive pulmonary disease
      were 15%, 6% and 3%, respectively. CONCLUSION: Data from systematic reviews and
      self-reported data on exposure provide opportunities to estimate the impact of
      ODs. For the Netherlands, they revealed substantial and varying attributions of
      work for prevalent diseases.

PMID- 30297529
TI  - Tuberculosis, mining and silica.

PMID- 30297531
TI  - Intratumoral Immunotherapy with XCL1 and sFlt3L Encoded in Recombinant Semliki
      Forest Virus-Derived Vectors Fosters Dendritic Cell-Mediated T-cell Cross
      Priming.
AB  - : Multiple lines of evidence indicate a critical role of antigen cross
      presentation by conventional BATF3-dependent type 1 classical dendritic cells
      (cDC1) in CD8-mediated antitumor immunity. Flt3L and XCL1, respectively,
      constitute a key growth/differentiation factor and a potent and specific
      chemoattractant for cDC1. To exploit their antitumor functions in local
      immunotherapy, we prepared Semliki Forest Virus (SFV)-based vectors encoding XCL1
      and soluble Flt3L (sFlt3L). These vectors readily conferred transgene expression
      to the tumor cells in culture and when engrafted as subcutaneous mouse tumor
      models. In syngeneic mice, intratumoral injection of SFV-XCL1-sFlt3L (SFV-XF)
      delayed progression of MC38- and B16-derived tumors. Therapeutic activity was
      observed and exerted additive effects in combination with anti-PD-1, anti-CD137,
      or CTLA-4 immunostimulatory mAbs. Therapeutic effects were abolished by CD8beta T
      cell depletion and were enhanced by CD4 T-cell depletion, but not by T regulatory
      cell predepletion with anti-CD25 mAb. Antitumor effects were also abolished in
      BATF3- and IFNAR-deficient mice. In B16-OVA tumors, SFV-XF increased the number
      of infiltrating CD8 T cells, including those recognizing OVA. Consistently,
      following the intratumoral SFV-XF treatment courses, we observed increased BATF3
      dependent cDC1 among B16-OVA tumor-infiltrating leukocytes. Such an intratumoral
      increase was not seen in MC38-derived tumors, but both resident and migratory
      cDC1 were boosted in SFV-XF-treated MC38 tumor-draining lymph nodes. In
      conclusion, viral gene transfer of sFlt3L and XCL1 is feasible, safe, and
      biologically active in mice, exerting antitumor effects that can be potentiated
      by CD4 T-cell depletion. SIGNIFICANCE: These findings demonstrate that transgenic
      expression of sFLT3L and XCL1 in tumor cells mediates cross-priming of, and
      elicits potent antitumor activity from, CD8 T lymphocytes, particularly in
      combination with CD4 T-cell depletion.

PMID- 30297532
TI  - DNA Polymerase Eta Prevents Tumor Cell-Cycle Arrest and Cell Death during
      Recovery from Replication Stress.
AB  - : Neoplastic transformation and genome instability are enhanced by replication
      stress, conditions that slow or stall DNA replication forks. Consequently, cancer
      cells require multiple enzymes and checkpoint signaling pathways to mitigate
      replication stress for their viability and proliferation. Targeting proteins that
      enhance cancer cell survival during replication stress is a recent approach in
      clinical strategies, especially when targets produce synthetic lethality. DNA
      polymerase eta (Pol eta) has many key functions in genome stability, particularly
      for translesion synthesis. Here we demonstrate that endogenous Pol eta displays
      significant protein induction and forms intense foci throughout the nucleus in
      response to replication stress induced by drugs that do not directly form DNA
      adducts. During replication stress, Pol eta-deficient cells displayed
      hyperactivation of the ATR replication checkpoint and arrested late in the cell
      cycle. During recovery from replication stress, Pol eta-deficient cells continue
      to display aberrant phenotypes, including delayed cell-cycle progression,
      apoptosis, and cell survival. Depletion or inhibition of ATR was synthetically
      lethal with Pol eta deficiency, particularly when tumor cells were treated with
      replication stress-inducing drugs. Together our data expand knowledge of the
      cellular environments that increase endogenous Pol eta expression beyond DNA
      damaging agents and demonstrate that Pol eta regulation is central to the
      replication stress response. Because Pol eta is aberrantly expressed in several
      tumor types, our results are critical for developing more effective chemotherapy
      approaches and identify coinhibition of Pol eta and ATR as a potential
      therapeutic strategy. SIGNIFICANCE: This study demonstrates that replication
      stress upregulates Pol eta (POLH) in tumor cells and reveals a role for Pol eta
      in tumor cell recovery following replication stress.

PMID- 30297530
TI  - Distinct roles of VE-cadherin for development and maintenance of specific lymph
      vessel beds.
AB  - Endothelial cells line blood and lymphatic vessels and form intercellular
      junctions, which preserve vessel structure and integrity. The vascular
      endothelial cadherin, VE-cadherin, mediates endothelial adhesion and is
      indispensible for blood vessel development and permeability regulation. However,
      its requirement for lymphatic vessels has not been addressed. During development,
      VE-cadherin deletion in lymphatic endothelial cells resulted in abortive
      lymphangiogenesis, edema, and prenatal death. Unexpectedly, inducible postnatal
      or adult deletion elicited vessel bed-specific responses. Mature dermal lymph
      vessels resisted VE-cadherin loss and maintained button junctions, which was
      associated with an upregulation of junctional molecules. Very different,
      mesenteric lymphatic collectors deteriorated and formed a strongly hyperplastic
      layer of lymphatic endothelial cells on the mesothelium. This massive
      hyperproliferation may have been favored by high mesenteric VEGF-C expression and
      was associated with VEGFR-3 phosphorylation and upregulation of the
      transcriptional activator TAZ Finally, intestinal lacteals fragmented into cysts
      or became highly distended possibly as a consequence of the mesenteric defects.
      Taken together, we demonstrate here the importance of VE-cadherin for lymphatic
      vessel development and maintenance, which is however remarkably vessel bed
      specific.

PMID- 30297533
TI  - Targeting PARP1 in XRCC1 deficient sporadic invasive breast cancer or pre
      invasive ductal carcinoma in situ induces synthetic lethality and
      chemoprevention.
AB  - Targeting PARP1 for synthetic lethality is a new strategy for breast cancers
      harboring germline mutations in BRCA. However, these mutations are rare, and
      reactivation of BRCA-mediated pathways may result in eventual resistance to PARP1
      inhibitor therapy. Alternative synthetic lethality approaches targeting more
      common sporadic breast cancers and pre-invasive ductal carcinoma in situ (DCIS)
      are desirable. Here we show that downregulation of XRCC1, which interacts with
      PARP1 and coordinates base excision repair, is an early event in human breast
      cancer pathogenesis. XRCC1-deficient DCIS were aggressive and associated with
      increased risk of local recurrence. Human invasive breast cancers deficient in
      XRCC1 and expressing high PARP1 levels also manifested aggressive features and
      poor outcome. The PARP1 inhibitor Olaparib was synthetically lethal in XRCC1
      deficient DCIS and invasive breast cancer cells. We conclude that targeting PARP1
      is an attractive strategy for synthetic lethality and chemoprevention in XRCC1
      deficient breast cancers, including pre-invasive DCIS.

PMID- 30297534
TI  - Pathologic Oxidation of PTPN12 Underlies ABL1 Phosphorylation in Hereditary
      Leiomyomatosis and Renal Cell Carcinoma.
AB  - : Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an inherited
      cancer syndrome associated with a highly aggressive form of type 2 papillary
      renal cell carcinoma (PRCC). Germline inactivating alterations in fumarate
      hydratase (FH) cause HLRCC and result in elevated levels of reactive oxygen
      species (ROS). Recent work indicates that FH-/- PRCC cells have increased
      activation of ABL1, which promotes tumor growth, but how ABL1 is activated
      remains unclear. Given that oxidation can regulate protein-tyrosine phosphatase
      (PTP) catalytic activity, inactivation of an ABL-directed PTP by ROS might
      account for ABL1 activation in this malignancy. Our group previously developed "q
      oxPTPome," a method that globally monitors the oxidation of classical PTPs. In
      this study, we present a refined q-oxPTPome, increasing its sensitivity by >10*.
      Applying q-oxPTPome to FH-deficient cell models showed that multiple PTPs were
      either highly oxidized (including PTPN12) or overexpressed. Highly oxidized PTPs
      were those with relatively high sensitivity to exogenous H2O2. Most PTP oxidation
      in FH-deficient cells was reversible, although nearly 40% of PTPN13 was
      irreversibly oxidized to the sulfonic acid state. Using substrate-trapping
      mutants, we mapped PTPs to their putative substrates and found that only PTPN12
      could target ABL1. Furthermore, knockdown experiments identified PTPN12 as the
      major ABL1 phosphatase, and overexpression of PTPN12 inhibited ABL1
      phosphorylation and HLRCC cell growth. These results show that ROS-induced
      oxidation of PTPN12 accounts for ABL1 phosphorylation in HLRCC-associated PRCC,
      revealing a novel mechanism for inactivating a tumor suppressor gene product and
      establishing a direct link between pathologic PTP oxidation and neoplastic
      disease. SIGNIFICANCE: This work identifies a novel mechanism of activation of
      the oncogenic kinase ABL1 via ROS-induced, oxidation-mediated inactivation of
      cognate protein tyrosine phosphatases.

PMID- 30297535
TI  - Pharmacological Inhibition of PARP6 Triggers Multipolar Spindle Formation and
      Elicits Therapeutic Effects in Breast Cancer.
AB  - : PARP proteins represent a class of post-translational modification enzymes with
      diverse cellular functions. Targeting PARPs has proven to be efficacious
      clinically, but exploration of the therapeutic potential of PARP inhibition has
      been limited to targeting poly(ADP-ribose) generating PARP, including PARP1/2/3
      and tankyrases. The cancer-related functions of mono(ADP-ribose) generating PARP,
      including PARP6, remain largely uncharacterized. Here, we report a novel
      therapeutic strategy targeting PARP6 using the first reported PARP6 inhibitors.
      By screening a collection of PARP compounds for their ability to induce mitotic
      defects, we uncovered a robust correlation between PARP6 inhibition and induction
      of multipolar spindle (MPS) formation, which was phenocopied by PARP6 knockdown.
      Treatment with AZ0108, a PARP6 inhibitor with a favorable pharmacokinetic
      profile, potently induced the MPS phenotype, leading to apoptosis in a subset of
      breast cancer cells in vitro and antitumor effects in vivo. In addition, Chk1 was
      identified as a specific substrate of PARP6 and was further confirmed by
      enzymatic assays and by mass spectrometry. Furthermore, when modification of Chk1
      was inhibited with AZ0108 in breast cancer cells, we observed marked upregulation
      of p-S345 Chk1 accompanied by defects in mitotic signaling. Together, these
      results establish proof-of-concept antitumor efficacy through PARP6 inhibition
      and highlight a novel function of PARP6 in maintaining centrosome integrity via
      direct ADP-ribosylation of Chk1 and modulation of its activity. SIGNIFICANCE:
      These findings describe a new inhibitor of PARP6 and identify a novel function of
      PARP6 in regulating activation of Chk1 in breast cancer cells.

PMID- 30297536
TI  - CDK1 Interacts with Sox2 and Promotes Tumor Initiation in Human Melanoma.
AB  - : Cancers are composed of heterogeneous subpopulations with various tumor
      initiating capacities, yet key stem cell genes associated with enhanced tumor
      initiating capacities and their regulatory mechanisms remain elusive. Here, we
      analyzed patient-derived xenografts from melanoma, colon, and pancreatic cancer
      tissues and identified enrichment of tumor-initiating cells in MHC class I-hi
      cells, where CDK1, a master regulator of the cell cycle, was upregulated.
      Overexpression of CDK1, but not its kinase-dead variant, in melanoma cells
      increased their spheroid forming ability, tumorigenic potential, and tumor
      initiating capacity; inhibition of CDK1 with pharmacologic agents reduced these
      characteristics, which was unexplained by the role of CDK1 in regulating the cell
      cycle. Proteomic analysis revealed an interaction between CDK1 and the
      pluripotent stem cell transcription factor Sox2. Blockade or knockdown of CDK1
      resulted in reduced phosphorylation, nuclear localization, and transcriptional
      activity of Sox2. Knockout of Sox2 in CDK1-overexpressing cells reduced CDK1
      driven tumor-initiating capacity substantially. Furthermore, GSEA analysis of
      CDK1hi tumor cells identified a pathway signature common in all three cancer
      types, including E2F, G2M, MYC, and spermatogenesis, confirming a stem-like
      nature of CDK1hi tumor cells. These findings reveal a previously unrecognized
      role for CDK1 in regulating tumor-initiating capacity in melanoma and suggest a
      novel treatment strategy in cancer via interruption of CDK1 function and its
      protein-protein interactions. SIGNIFICANCE: These findings uncover CDK1 as a new
      regulator of Sox2 during tumor initiation and implicate the CDK1-Sox2 interaction
      as a potential therapeutic target in cancer.

PMID- 30297537
TI  - Hemorrhagic transformation is associated with poor functional outcome in patients
      with acute ischemic stroke due to a large vessel occlusion.
AB  - BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a complication that
      may cause neurological deterioration in patients with acute ischemic stroke.
      Various radiological subtypes of HT can be distinguished. Their influence on
      functional outcome is currently unclear. The purpose of this study was to assess
      the associations between HT subtypes and functional outcome in acute ischemic
      stroke patients with proven large vessel occlusion included in the MR CLEAN trial
      (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute
      Ischemic stroke in The Netherlands). METHODS: All patients with follow-up imaging
      were included. HT was classified on follow-up CT scans according to the European
      Cooperative Acute Stroke Study II classification. Functional outcome was assessed
      using the modified Rankin Scale (mRS) 90 days after stroke onset. Ordinal
      logistic regression analysis with adjustment for potential confounders was used
      to determine the association of HT subtypes with functional outcome. RESULTS: Of
      478 patients, 222 had HT. Of these, 76 (16%) patients were classified as
      hemorrhagic infarction type 1, 71 (15%) as hemorrhagic infarction type 2, 36 (8%)
      as parenchymal hematoma type 1, and 39 (8%) as parenchymal hematoma type 2.
      Hemorrhagic infarction type 2 (adjusted common OR (acOR) 0.54, 95% CI: 0.32 to
      0.89) and parenchymal hematoma type 2 (acOR 0.37, 95% CI 0.17 to 0.78) were
      significantly associated with a worse functional outcome. Hemorrhagic infarction
      type 1 and parenchymal hematoma type 1 were not significantly associated,
      although their point estimates pointed in the direction of worse outcome.
      CONCLUSION: This study suggests that parenchymal hematoma type 2 is relevant for
      functional outcome after an acute ischemic stroke, and smaller HTs might also
      influence long term functional outcome. TRAIL REGISTRATION NUMBER:
      ISRCTN10888758.

PMID- 30297538
TI  - Revisiting the therapeutic time window dogma: successful thrombectomy 6 days
      after stroke onset.
AB  - Stroke is the leading cause of serious long-term disability in the USA. Recent
      clinical trials, DAWN and DEFUSE 3, have expanded the endovascular therapeutic
      time window which has been adopted by the American Heart Association stroke
      guideline. However, there continues to be a dilemma as to what is the best
      approach for patients who present beyond the time window set by these trials and
      the current guideline. The interval from arterial occlusion to completion of
      brain tissue infarction varies from patient to patient and depends on the actual
      time and also a physiological clock or a tissue time window. Offering
      endovascular treatment based solely on a rigid time criterion excludes patients
      who may have a clinical benefit because of potentially salvageable tissue. We
      present a case of a patient who underwent successful stroke thrombectomy 6 days
      after stroke onset.

PMID- 30297539
TI  - SAFE study (Safety and efficacy Analysis of FRED Embolic device in aneurysm
      treatment): 1-year clinical and anatomical results.
AB  - BACKGROUND AND PURPOSE: Flow diversion is an innovative and increasingly used
      endovascular treatment for intracranial aneurysms. Its initial evaluation with
      the first devices available showed good efficacy of this treatment with variable
      safety results. The Flow Direction Endoluminal Device (FRED) has a specific
      design and was evaluated in a single-arm, multicenter, prospective, Good Clinical
      Practice study: SAFE (Safety and efficacy Analysis of FRED Embolic device in
      aneurysm treatment). This analysis reports clinical results at 1 year and
      anatomical results at 6 months and 1 year. METHODS: Patients with unruptured and
      recanalized aneurysms located in the anterior circulation treated with FRED and
      FRED Jr were prospectively included. A Clinical Event Committee and a Core
      Laboratory independently evaluated clinical outcome and anatomical results.
      RESULTS: Thirteen interventional neuroradiology centers included 103
      patients/aneurysms. Aneurysm locations were supraclinoid internal carotid artery
      (ICA) in 71 (68.9%), cavernous ICA in 15 (14.6%), anterior cerebral or anterior
      communicating artery in 9 (8.7%), and middle cerebral artery in 8 (7.8%). Most
      aneurysms were small (<10 mm) in 71 patients (68.9%). Cumulative 1-year mortality
      and morbidity rates were 2/103 (1.9%) and 3/103 (2.9%), respectively, one death
      being related to cancer. At 1 year, anatomical results were: complete occlusion
      in 66/90 patients (73.3%), neck remnant in 7/90 patients (7.8%), and aneurysm
      remnant in 17/90 patients (18.9%). CONCLUSIONS: SAFE study analysis at 1 year
      confirms the excellent safety profile of the FRED device for aneurysm treatment,
      with low morbidity and mortality rates (2.9% and 1.9%, respectively) and
      demonstrates its efficacy (adequate occlusion in 73/90 (81.1%)). CLINICAL TRIAL
      REGISTRATION: Unique identifier: NCT02921698; Results.

PMID- 30297540
TI  - Vertebral body stent augmentation to reconstruct the anterior column in
      neoplastic extreme osteolysis.
AB  - BACKGROUND: Extensive lytic lesions of the vertebral body (VB) increase risk of
      fracture and instability and require stabilization of the anterior column.
      Vertebral augmentation is an accepted treatment option, but when osteolysis has
      extensively destroyed the VB cortical boundaries (a condition herein defined as
      'extreme osteolysis'), the risk of cement leakage and/or insufficient filling is
      high. Vertebral body stents (VBSs) might allow partial restoration of VB height,
      cement containment, and reinforcement, but their use in extreme osteolysis has
      not been investigated. OBJECTIVE: To assess retrospectively the feasibility and
      safety of VBS augmentation in patients with 'extreme osteolysis' of the VB.
      METHODS: We retrospectively analyzed 41 treated vertebrae (from T1 to L5). VB
      reconstruction was assessed on postprocedure CT images and rated on a qualitative
      4-point scale (poor-fair-good-excellent). Clinical and radiological follow-up was
      performed at 1 month and thereafter at intervals in accordance with oncological
      protocols. RESULTS: VBS augmentation was performed at 12 lumbar and 29 thoracic
      levels, with bilateral VBS in 23/41. VB reconstruction was judged satisfactory
      (good or excellent) in 37/41 (90%) of levels. Bilateral VBS received higher
      scores than unilateral (p=0.057, Pearson's X2). We observed no periprocedural
      complications. Cement leaks (epidural or foraminal) occurred at 5/41 levels
      (12.2%) without clinical consequences. Follow-up data were available for 27/29
      patients, extending beyond 6 months for 20 patients (7-28 months, mean 15.3
      months). VBS implant stability was observed in 40/41 cases (97.5%). CONCLUSIONS:
      Our results support the use of VBS as a minimally invasive, safe and effective
      option for reconstructing the anterior column in prominent VB osteolysis.

PMID- 30297541
TI  - Mothership versus drip and ship for thrombectomy in patients who had an acute
      stroke: a systematic review and meta-analysis.
AB  - BACKGROUND: The effectiveness of mechanical thrombectomy (MT) in acute ischemic
      stroke due to large vessel occlusion is time-dependent. While only stroke centers
      with endovascular capabilities perform MT, many patients who had a stroke
      initially present to the closest primary stroke centers capable of administering
      earlier intravenous thrombolysis, and then require to be transferred to a
      comprehensive stroke center for MT. PURPOSE: To compare the outcomes of this care
      pathway (drip and ship (DS)) with that whereby patients are directly transferred
      to a comprehensive stroke center (mothership (MS)). METHODS: We performed a
      systematic review and meta-analysis of published studies using several electronic
      databases to determine whether successful reperfusion (modified Thrombolysis In
      Cerebral Infarction >=2b), functional independence at 90 days (modified Rankin
      Scale score <=2), symptomatic intracranial hemorrhage, and 90-day mortality
      differed between those who underwent MT with the DS or the MS treatment pathway.
      Outcomes were meta-analyzed and the results expressed as adjusted relative risk
      (aRR) for the primary analysis and unadjusted relative risk (uRR) for secondary
      analysis. RESULTS: Eight studies including 2068 patients were selected, including
      one study reporting results fully adjusted for baseline characteristics. Patients
      undergoing MS had better functional independence than those undergoing DS
      (uRR=0.87, 95% CI 0.81 to 0.93; aRR=0.87, 95% CI 0.77 to 0.98). No difference was
      found between the treatment pathways in successful reperfusion (uRR=1.05, 95% CI
      0.95 to 1.15; aRR=1.00, 95% CI 0.92 to 1.10), symptomatic intracranial hemorrhage
      (uRR=1.37, 95% CI 0.91 to 2.06; aRR, 1.53, 95% CI 0.79 to 2.98), and 90-day
      mortality (uRR=1.00, 95% CI 0.84 to 1.19; aRR=1.21, 95% CI 0.89 to 1.64).
      CONCLUSIONS: Patients who had an acute ischemic stroke admitted directly to a
      comprehensive stroke center (MS patients) with endovascular capacities may have
      better 90-day outcomes than those receiving DS treatment. However, major
      limitations of current evidence (ie, retrospective studies and selection bias)
      suggest a need for adequately powered studies. Multicenter randomized controlled
      trials are expected to answer this question.

PMID- 30297542
TI  - The semiotics of distal thrombectomy: towards a TICI score for the target vessel.

PMID- 30297543
TI  - The safety and effectiveness of the LVIS stent system for the treatment of wide
      necked cerebral aneurysms: final results of the pivotal US LVIS trial.
AB  - INTRODUCTION: The LVIS stent system (LVIS and LVIS Junior) is a self-expanding,
      retrievable, microstent system indicated for the treatment of wide-necked
      cerebral aneurysms (WNAs). The present pivotal study was performed to evaluate
      the safety and effectiveness of this device. METHODS: The US LVIS pivotal trial
      was a prospective, multicenter, single-arm, interventional study conducted at 21
      US centers. The study enrolled 153 adults with WNAs of the anterior and posterior
      circulations. The study was conducted under good clinical practices and included
      independent adjudication of all adverse events. The primary effectiveness
      endpoint was defined as successful aneurysm treatment with the LVIS System as
      evidenced by complete (100%) aneurysm occlusion at 12 months on conventional
      angiography without retreatment and without significant (>=50%) stenosis of the
      treated artery at 12 months as determined by an independent core laboratory. The
      primary safety endpoint was defined as the rate of stroke or death within 30
      days, or ipsilateral stroke or neurologic death with 12 months. RESULTS: One
      hundred and fifty-three patients enrolled at 21 investigational sites underwent
      attempted LVIS-assisted coil embolization. The mean age was 58.3+/-10.5 years and
      the majority of the participants (110/153, 71.9%) were female. Fifty-seven
      aneurysms (57/153, 37.3%) arose from the anterior cerebral artery, 43 (43/153,
      28.1%) from the internal carotid artery, 17 (17/153, 11.1%) from the middle
      cerebral artery, 27 (27/153, 17.6%) from the basilar artery, six (6/153,3.9 %)
      from the PCA, and two from the vertebral artery. A single aneurysm arose from the
      superior cerebellar artery. The mean aneurysm dome height was 6.0+/-2.2 mm and
      mean width 5.5+/-2.3 mm. Mean neck width was 4.2+/-1.4 mm. A total of 22
      participants presented for re-treatment of a previously ruptured (>30 days prior
      to treatment) target aneurysm. The primary effectiveness endpoint was observed in
      70.6% (108/153) in the intent to treat population (ITT). Of the evaluable
      participants with follow-up 12-month angiography, 79.1 % (110/139) demonstrated
      complete occlusion- 92.1% (128/139) in this population demonstrated >=95%
      occlusion and 95% demonstrated >=90% occlusion (132/139). Eight participants
      (5.2%, 8/153) had at least one primary safety event in the ITT population.
      CONCLUSION: The LVIS stent system allows safe and highly effective coil
      embolization of WNAs. CLINICAL REGISTRATION NUMBER: NCT01793792.

PMID- 30297545
TI  - Crystalline transformers: more within than meets the eye.
AB  - Studies of phase transitions in molecular crystals are becoming more commonplace
      as improvements in instrumentation and technique enable more efficient
      exploration of the behavior of samples with varying external conditions, usually
      temperature. This scientific commentary provides contextual background on this
      type of study, with reference to an article on transformations in a ferrocenyl
      acetylide-gold(I) complex [Makal (2018). Acta Cryst. B74, 427-435].

PMID- 30297544
TI  - Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute
      cholecystitis in high risk patients (CHOCOLATE): multicentre randomised clinical
      trial.
AB  - OBJECTIVE: To assess whether laparoscopic cholecystectomy is superior to
      percutaneous catheter drainage in high risk patients with acute calculous
      cholecystitis. DESIGN: Multicentre, randomised controlled, superiority trial.
      SETTING: 11 hospitals in the Netherlands, February 2011 to January 2016.
      PARTICIPANTS: 142 high risk patients with acute calculous cholecystitis were
      randomly allocated to laparoscopic cholecystectomy (n=66) or to percutaneous
      catheter drainage (n=68). High risk was defined as an acute physiological
      assessment and chronic health evaluation II (APACHE II) score of 7 or more. MAIN
      OUTCOME MEASURES: The primary endpoints were death within one year and the
      occurrence of major complications, defined as infectious and cardiopulmonary
      complications within one month, need for reintervention (surgical, radiological,
      or endoscopic that had to be related to acute cholecystitis) within one year, or
      recurrent biliary disease within one year. RESULTS: The trial was concluded early
      after a planned interim analysis. The rate of death did not differ between the
      laparoscopic cholecystectomy and percutaneous catheter drainage group (3% v 9%,
      P=0.27), but major complications occurred in eight of 66 patients (12%) assigned
      to cholecystectomy and in 44 of 68 patients (65%) assigned to percutaneous
      drainage (risk ratio 0.19, 95% confidence interval 0.10 to 0.37; P<0.001). In the
      drainage group 45 patients (66%) required a reintervention compared with eight
      patients (12%) in the cholecystectomy group (P<0.001). Recurrent biliary disease
      occurred more often in the percutaneous drainage group (53% v 5%, P<0.001), and
      the median length of hospital stay was longer (9 days v 5 days, P<0.001).
      CONCLUSION: Laparoscopic cholecystectomy compared with percutaneous catheter
      drainage reduced the rate of major complications in high risk patients with acute
      cholecystitis. TRIAL REGISTRATION: Dutch Trial Register NTR2666.

PMID- 30297546
TI  - The puzzling structure of Cu5FeS4 (bornite) at low temperature.
AB  - The crystal structure of Cu5FeS4 (bornite) has been investigated using
      synchrotron X-ray powder diffraction at temperatures between 10 and 275 K.
      Diffraction data confirm that bornite crystallizes in the orthorhombic space
      group Pbca at 275 K. The unit-cell volume decreases continuously on cooling, but
      undergoes an abrupt contraction below ~65 K, where a first-order Pbca->Pca21
      structural transition takes place. The primary active mode yielding the observed
      ordered structure corresponds to the irreducible representation Gamma2-, with
      wavevector (0,0,0). Pair distribution function analysis shows strong
      discrepancies between the local and the average structure. The average Fe-S bond
      length obtained through the EXAFS local probe is consistent with the values
      independently provided by X-ray powder diffraction data, strongly supporting the
      preferred location of Fe.

PMID- 30297547
TI  - Azulene revisited: solid-state structure, invariom modeling and lattice-energy
      minimization of a classical example of disorder.
AB  - The molecular and solid-state structure of azulene both raise fundamental
      questions. Therefore, the disordered crystal structure of azulene was re-refined
      with invariom non-spherical atomic scattering factors from new single-crystal X
      ray diffraction data with a resolution of d = 0.45 A. An unconstrained refinement
      results in a molecular geometry with Cs symmetry. Refinements constrained to
      fulfill C2v symmetry, as observed in the gas phase and in high-level ab initio
      calculations, lead to similar figures of merit and residual densities as
      unconstrained ones. Such models are consistent with the structures from microwave
      spectroscopy and electron diffraction, albeit they are not the same. It is shown
      that for the disorder present in azulene, the invariom model describes valence
      electron density as successfully as it does for non-disordered structures,
      although the disorder still leads to high correlations mainly between positional
      parameters. Lattice-energy minimizations on a variety of ordered model structures
      using dispersion-corrected DFT calculations reveal that the local deviations from
      the average structure are small. Despite the molecular dipole moment there is no
      significant molecular ordering in any spatial direction. A superposition of all
      ordered model structures leads to a calculated average structure, which explains
      not only the experimental determined atomic coordinates, but also the apparently
      unusual experimental anisotropic displacement parameters.

PMID- 30297548
TI  - Triethylphosphine as a molecular gear - phase transitions in ferrocenyl-acetylide
      gold(I).
AB  - A sequence of two discontinuous phase transitions, occurring just above 125 K and
      148 K, has been observed for a ferrocenyl-acetylide-gold(I) complex with
      triethylphosphine, structure (1), by means of a multi-temperature single-crystal
      X-ray diffraction technique. Three distinct phases have been identified. The high
      temperature alpha and low-temperature gamma phases share the same space group
      Pbca, whereas the intermediate beta phase is in the Pb21a subgroup of Pbca. In
      all phases molecules of (1) form well defined double layers, with PEt3 groups
      interlocking in planes perpendicular to c. On the molecular level, both phase
      transitions involve almost uniquely a conformational change of triethylphosphine:
      a gear-like rotation around the P-Au axis and concerted flips of the ethyl
      moieties. The mechanism of these transitions may be imagined as initiated by a
      rotation of a single PEt3 group in a double layer (a single gear movement),
      followed by adjacent phosphines adjusting their conformations as a result of
      steric strain. The structural changes underlying phase transitions are
      sequential, occurring layer-wise, the gamma->beta transition involving
      approximately every other layer in the crystal lattice, the beta->alpha yielding
      a total conformation change. The sequence of phase transitions results in a
      noticeable contraction of the crystal cell volume.

PMID- 30297549
TI  - Inflexible stoichiometry in bulk pyrite FeS2 as viewed by in situ and high
      resolution X-ray diffraction.
AB  - Non-stoichiometry is considered to be one of the main problems limiting iron
      pyrite, FeS2, as a photovoltaic absorber material. Although some historical
      diffraction experiments have implied a large solubility range of FeS2-delta with
      delta up to 0.25, the current consensus based on calculated formation energies of
      intrinsic defects has lent support to line-compound behavior. Here it is shown
      that pyrite stoichiometry is relatively inflexible in both reductive conditions
      and in autogenous sulfur partial pressure, which produces samples with precise
      stoichiometry of FeS2 even at different Fe/S ratios. By properly standardizing in
      situ gas-flow X-ray diffraction measurements, no significant changes in the
      lattice parameter of FeS2 can be resolved, which portrays iron pyrite as prone to
      forming sulfur-deficient compounds, but not intrinsic defects in the manner of
      NiS2-delta.

PMID- 30297550
TI  - Determination of the miscibility gap in the solid solutions series of
      methylammonium lead iodide/chloride.
AB  - Perovskites are widely known for their enormous possibility of elemental
      substitution, which leads to a large variety of physical properties. Hybrid
      perovskites such as CH3NH3PbI3 (MAPbI3) and CH3NH3PbCl3 (MAPbCl3) are perovskites
      with an A[XII]B[VI]X[II]3-structure, where A is an organic molecule, B is a
      lead(II) cation and X is a halide anion of iodine or chlorine. Whereas MAPbCl3
      crystallizes in the cubic space group Pm{?overline 3}m, MAPbI3 is in the
      tetragonal space group I4/mcm. The substitution of I by Cl leads to an increased
      tolerance against humidity but is challenging or even impossible due to their
      large difference in ionic radii. Here, the influence of an increasing Cl content
      in the reaction solution on the miscibility of the solid solution members is
      examined systematically. Powders were synthesized by two different routes
      depending on the I:Cl ratio. High-resolution synchrotron X-ray data are used to
      establish values for the limits of the miscibility gap which are 3.1 (1.1) mol%
      MAPbCl3 in MAPI and 1.0 (1) mol% MAPbI3 in MAPCl. The establishment of relations
      between average pseudo-cubic lattice parameters for both phases allows a
      determination of the degree of substitution from the observed lattice parameters.

PMID- 30297551
TI  - Crystal packing control of a trifluoromethyl-substituted furan/phenylene co
      oligomer.
AB  - Furan/phenylene co-oligomer single crystals are considered as future materials
      for organic optoelectronics. Here, the effects of trifluoromethyl substituents on
      the crystallization, structure and optical properties of furan/phenylene co
      oligomer 1,4-bis{5-[4-(trifluoromethyl)phenyl]furan-2-yl}benzene are studied
      systematically. The solution growth methods and physical vapor transport result
      in the formation of three polymorphs depending on the growth method and the
      solvent. Single-crystal X-ray analysis reveals the crystal structures to
      correspond to H-, J- or mixed aggregates. All obtained crystals exhibit high
      photoluminescence efficiency and have optical properties which strongly depend on
      the crystal packing. Variable-temperature X-ray powder diffraction analysis shows
      the thermal transition of two forms (H- and J-aggregates) into a third one (mixed
      aggregate). Terminal trifluoromethyl groups induce weak intermolecular
      interactions which control the crystal packing and optical properties of co
      oligomer single crystals.

PMID- 30297552
TI  - Melting point, molecular symmetry and aggregation of tetrachlorobenzene isomers:
      the role of halogen bonding.
AB  - Tetrachlorobenzenes represent one of the best known, but not yet fully
      understood, group of isomers of the structure-melting point relationship. The
      differences in melting temperatures of these structurally related compounds were
      rationalized in terms of the hierarchy and nature of formed noncovalent
      interactions, and the molecular aggregation that is influenced by molecular
      symmetry. The highest melting point is associated with the highly symmetric
      1,2,4,5-tetrachlorobenzene isomer. The structures of less symmetrical 1,2,3,4
      tetrachlorobenzene and 1,2,3,5-tetrachlorobenzene, determined at 270 and 90 K,
      show a distinct pattern of halogen bonds, characterized by the different numbers
      and types of interactions. The evolution of Cl...Cl/H distances with temperature
      indicates the attractive character of intermolecular interactions and their
      importance to the structural and thermodynamic parameters of isomeric compounds.
      The favoured Cl...Cl halogen bonds were found to play a decisive role in
      differentiating the melting temperatures of tetrachlorobenzene isomers. It was
      also found that, besides the molecular symmetry and ability to form specific
      intermolecular interactions, both the type and the distribution of interactions
      are the important factors responsible for the melting behaviour of the studied
      isomers. The observed preferences, in tetrachlorobenzenes, for the formation of
      specific noncovalent interactions correspond to the distribution of calculated
      partial atomic charges and to the magnitudes of electrostatic potential on the
      molecular surfaces as well as correlate with the enthalpy of melting parameters.

PMID- 30297553
TI  - Rheumatoid arthritis in temporo-mandibular joint: A review.
AB  - This article summarizes the temporomandibular joint (TMJ) rheumatoid arthritis
      (RA). In particular, TMJ-RAs are collected in a short summary by examining every
      aspect of RA; the treatment of TMJ-RA is also briefly mentioned. TMJ-RA is
      usually characterized by bilateral pain, tenderness and swelling, and limitation
      of jaw movements. Due to these symptoms, patients may experience limitations in
      their daily activities, such as eating, speaking, and swallowing. MEDLINE and
      Scopus databases were searched electronically using the terms "temporomandibular
      joint" and "rheumatoid arthritis." The electronic search includes articles or
      books published in English and December 2017. A search of the reference lists of
      selected articles was also carried out.

PMID- 30297555
TI  - The accuracy of risk malignancy index in prediction of malignancy in women with
      adnexal mass in Basrah, Iraq.
AB  - Background: Adnexal masses indicate a variety of gynecological and
      nongynecological disorders, which may be benign or malignant. Early detection of
      malignancy is crucial to a proper planning of treatment and improvement of
      survival. Objective: To determine the accuracy of risk of malignancy index (RMI)
      in prediction of malignant adnexal mass. Subjects and Methods: This was a
      prospective multicenter study which included 101 women with adnexal masses. RMI2
      with cutoff value of 200 was used to discriminate between benign and malignant
      tumors. Histopathological examination was used to confirm the final diagnosis.
      Results: Out of the studied women, 20.8% proved to have malignant tumors. The RMI
      showed a sensitivity of 100%, a specificity of 96.2%, a positive predictive value
      of 87.5%, and a negative predictive value (NPV) of 100%. The RMI identified
      malignant cases more accurately than any individual criterion in diagnosing
      ovarian cancer. The receiver operating characteristic analysis showed that the
      area under the curve of the RMI, CA 125, ultrasound, and menopausal status were
      significantly high with values of 1.0, 0.99, 0.86, and 0.85, respectively.
      Conclusion: The RMI is a simple sensitive, practical, and reliable tool in
      preoperative discrimination between benign and malignant adnexal masses that can
      facilitate selection of cases for timely referral to oncology center.

PMID- 30297554
TI  - Digital evaluation of the dimensional accuracy of four different implant
      impression techniques.
AB  - Aims: The aim of this study was to compare the dimensional accuracy of four
      different implant impression techniques of a mandibular edentulous model with
      five parallel implants. Materials and Methods: Five dental implants were placed
      in an edentulous mandibular model in parallel. A total of forty impressions were
      obtained using four different impression techniques. In Group 1 (G1) and Group 2
      (G2), closed tray impressions with and without plastic caps, respectively, were
      used. In Group 3 (G3) and Group 4 (G4), open tray impressions with a direct
      splinted technique and an improved direct splinted technique, respectively, were
      used. All the impressions were poured with Type IV dental stone. Master model and
      study casts were scanned with a laser optical scanner and aligned by observing
      the superpositions of the anatomical landmarks using a software program.
      Statistical Analysis Used: Fifty measurements of the apical, coronal, and angular
      discrepancies of the master and study casts were obtained (n = 50) and
      statistically analyzed using a one-way analysis of variance and post hoc (least
      significant difference ) and Friedman's tests. Results: The lowest accuracy was
      obtained from G2 when the angular (1.48 degrees ), coronal (0.32 MUm), and apical
      (0.14 MUm) deviations were tested (P < 0.05), whereas no statistically
      significant differences were found among the other groups (P < 0.05).
      Conclusions: In cases with five parallel mandibular implants, improved accuracy
      was achieved using the direct splinted technique, the improved direct splinted
      technique, or the closed tray impression technique with snap on plastic caps.

PMID- 30297556
TI  - A profile of individuals accompanying patients in the emergency department: An
      analysis of 5046 cases.
AB  - Background: There has been no comprehensive study on identifying the
      sociocultural characteristics and the factors affecting the number of relatives
      and/or friends accompanying patients. The purpose of this study was to identify
      these sociocultural characteristics and the factors affecting this. Materials and
      Methods: The research was designed as a cross-sectional, one-to-one interview
      study. A study population representing one in three patients aged over 18 years
      and presenting consecutively to the emergency department over a 1-month period
      was constituted with systematic sampling. A sample size of at least 4483 patients
      was planned with a 1% margin of error and 90% power. Results: Two thousand nine
      hundred and fifty (58.5%) of the 5046 patients included in the study were male.
      Patients' mean age was 38.4 +/- 17.4 years (median 34 years). At least one friend
      or relative accompanied 3690 (73.1%) patients, and the mean number of
      accompanying individuals was 1.50. A higher level of accompaniment and a higher
      mean number of accompanying individuals were determined in patients presenting to
      the emergency department outside working hours, with altered mental state,
      attending hospital for the first time, with chronic disease, requiring
      hospitalization, in illiterate patients, in patients who had not studied at
      university, in patients aged 65 or over, and in patients presenting to hospital
      and the emergency department for the first time compared to other parameters
      (<0.01 for all). Conclusion: The number of people accompanying patients increases
      with sociocultural factors such as gender, age, literacy, and education level. In
      addition, similar increase can be observed with patients coming to emergency
      department by ambulance or having a chronic disease or arrive with lost
      consciousness.

PMID- 30297557
TI  - Chemical analysis of uroliths: A two-center study of doctors' practice and
      perspective in South-East, Nigeria.
AB  - Introduction: Urolithiasis is a global disease condition secondary to a variety
      of factors, and sometimes associated with serious complications. Determination of
      stone composition is important in delineating causative factors. Knowledge of
      causative and precipitating factors aids patient management and prevention of
      recurrence. Objective: The authors' aim was to evaluate the practice and
      perspective of doctors regarding chemical analysis of stones in management of
      urolithiasis. Materials and Methods: This comparative cross-sectional study was
      done between December 2016 and May 2017 in two teaching hospitals in South-East,
      Nigeria. Data were collected using self-administered questionnaires. Results: In
      all, 88 doctors with mean (standard deviation) age of 37.3 (9.5) years
      participated in the study. Urinary bladder stones were the most frequently
      managed, 51 (58.0%); 45 (51.1%) participants do not routinely send stones for
      chemical analysis. All respondents (100%) agreed that stone analysis is
      beneficial to patient management. Conclusion: This study showed that in spite of
      all respondents affirming that chemical analysis of uroliths is beneficial to
      patient management, more than half of respondents do not routinely send stones
      for analysis.

PMID- 30297558
TI  - Frequency of audiological complaints in patients with fibromyalgia syndrome and
      its relationship with oxidative stress.
AB  - Aim: Central sensitization-related neuroaudiological symptoms are frequently seen
      in patients with fibromyalgia syndrome (FMS). This study aimed to evaluate the
      audiological signs and symptoms in patients with FMS and explore their
      relationship with oxidative stress markers. Methods: This prospective controlled
      cross-sectional study compared the serum myeloperoxidase, superoxide dismutase,
      glutathione peroxidase (GPx), nitric oxide (NO), and malondialdehyde (MDA)
      concentrations in 44 patients with FMS diagnosed according to the 2010 American
      College of Rheumatology criteria and 44 healthy volunteers. FMS severity was
      assessed using the visual analog scale and Fibromyalgia Impact Questionnaire. An
      audiological assessment including vocalizations, vertigo, balance problems, and
      hearing problems was done to all participants. Results: The two groups were of
      similar age (P = 0.24), gender (P = 0.40), and weight distribution (P = 0.6).
      Vertigo, tinnitus, hearing, and balance complaints (P = 0.01/P = 0.00/P = 0.00/P
      = 0.01) were significantly higher in the FMS group. All subunits and total scores
      of dizziness handicap inventory were significantly higher (P = 0.00/P = 0.00/P =
      0.01/P = 0.01) in the FMS group. An antioxidant GPx and oxidant parameters such
      as NO and MDA were found to be significantly higher (P = 0.00/P = 0.01/P = 0.02).
      The hearing assessments at frequencies between 250 and 12,000 Hz showed a
      significant difference between the two groups (high hearing frequencies in the
      FMS group) in audiometry. No significant difference was found between the two
      groups in terms of the presence of stabilo-acoustic reflex, intraaural pressure,
      and compliance (P = 0.18/P = 0.33/P = 0.41) in tympanogram. Conclusions: Patients
      with FMS have high levels of oxidative stress markers (GPx, NO, and MDA), highly
      frequent audiological symptoms with high hearing frequencies in audiometry,
      independent of disease severity.

PMID- 30297559
TI  - Preoperative Vitamin D levels and respiratory complications of general
      anesthesia.
AB  - Aims: This research aims to investigate whether there is a correlation between
      the respiratory complications occurring in patients under general anesthesia and
      preoperative Vitamin D levels. Settings and Design: The study was a prospective
      observational study. Materials and Methods: This study included 95 adult cases.
      The cases had total 25-hydroxyvitamin D (25OHD) levels identified in blood
      samples before the operation. Patients given routine general anesthesia and were
      assessed in terms of respiratory complications during anesthesia induction,
      extubation, anesthesia recovery, and the first 24-h postoperative. Statistical
      Analysis Used: The Shapiro-Wilk test, Student's-t-test, one-way ANOVA test,
      Pearson correlation coefficient, and Chi-square tests were used. Results: The
      mean 25OHD vitamin level identified in the preoperative period was 13.00 +/- 6.57
      ng/mL, with 25OHD vitamin levels found to be significantly low in female cases
      compared to male cases (P < 0.05). There was a statistically significant negative
      relationship between age and 25OHD vitamin levels identified (P = 0.045). When
      assessed in terms of surgery types, there was no significant difference found in
      Vitamin D levels in terms of surgery type. When examined for complications in the
      induction, extubation period, and postoperative recovery period, there was a
      significant difference identified between 25OHD vitamin levels and these
      complications (P < 0.01). Conclusions: This research observed that patients with
      low preoperative 25OHD vitamin levels encountered respiratory complications
      related to general anesthesia more often. Especially, in the early postoperative
      period, there is a very significant difference between complications and low
      25OHD vitamin levels.

PMID- 30297560
TI  - Effect of chitosan on sealer penetration into the dentinal tubules.
AB  - Objective: The objective of this study is to compare the effectiveness of final
      irrigation with chitosan, ethylenediaminetetraacetic acid (EDTA), and citric acid
      (CA) on a resin-based sealer (AH plus sealer [Dentsply DeTrey, Konstanz,
      Germany]) penetration into dentinal tubules using confocal laser scanning
      microscopy. Materials and Methods: Seventy recently extracted human mandibular
      premolars were instrumented and irrigated with sodium hypochlorite (NaOCl), then
      divided into four groups according to the final irrigation regimen used: (1) the
      EDTA group: 17% EDTA + 2.5% NaOCl, (2) the CA group: 10% CA + 2.5% NaOCl, (3) the
      chitosan group: 0.2% chitosan + 2.5% NaOCl, and (4) the control group: 2.5%
      NaOCl. All teeth were obturated using the cold lateral condensation technique
      with gutta-percha and AH Plus sealer labeled with fluorescent dye. The apical 2
      mm of specimen was discarded, and slices were obtained for apical, middle, and
      coronal thirds of the root with 1 mm intervals. Maximum, mean, and percentage of
      sealer penetration (SP) inside tubules were measured using confocal laser
      scanning microscopy. Results: The percentage of SP was significantly higher in
      chitosan, EDTA, and CA group than control group for coronal thirds (P < 0.05),
      whereas there was no significant difference among all groups for middle and
      apical thirds. Chitosan and EDTA showed increased mean values of SP depth for
      middle thirds (P < 0.05). In all sections, the maximum depth of SP was
      significantly lower in EDTA group than other groups (P < 0.05). Conclusions:
      Chitosan, EDTA, and CA significantly improved the percentage of SP for coronal
      thirds.

PMID- 30297562
TI  - Primary principles in developing scale with Rasch analysis: Portfolio anxiety
      assessment.
AB  - Background: Rasch model is a useful method for developing a new scale. This study
      aims to determine the fitting between data obtained from answers for a portfolio
      anxiety scale and Rasch model and describes how the scale can be modified to
      increase the fitting through different steps. Materials and Methods: A portfolio
      scale was applied to 171 students of the Faculty of Medicine, Ondokuz Mayis
      University. The partial credit model was used, and fit statistics were assessed
      to determine the fitting of the data to Rasch model. Person separation index
      (PSI) was used for reliability. Results: For a satisfaction subscale, the average
      item fit residual value was 0.47 and the average person fit residual value was 
      0.29. For the item-trait chi2 interaction, P = 0.655 and PSI = 0.81. For a
      writing anxiety subscale, the average item fit residual value was 0.08 and the
      average person fit residual value was -0.24. For the item-trait chi2 interaction,
      P = 0.698 and PSI = 0.73. For a reflection anxiety subscale, the average item fit
      residual value was 0.64 and the average item fit residual value was 0.64. For the
      item-trait chi2 interaction, P = 0.195 and PSI = 0.73. Conclusion: The validity
      and reliability of Rasch analysis portfolio scale were analyzed, and items that
      worked well were included in the study. The results show that Rasch model
      provides a more accurate analysis for developing and adapting scales. Both the
      fit statistics and fit graphs help improve the analyses.

PMID- 30297561
TI  - Effect of green gold nanoparticles synthesized with plant on the flexural
      strength of heat-polymerized acrylic resin.
AB  - Purpose: The aim of this study was to investigate the effect of gold nanoparticle
      on the flexural strength of polymethyl methacrylate (PMMA). Materials and
      Methods: PMMA specimens (65 mm * 10 mm * 3.3 mm) containing different sizes (45
      nm, 55 nm, and 65 nm) and concentrations (0.05% and 0.2%) of gold nanoparticles
      were prepared, along with a control group containing no added nanoparticles.
      Flexural strength of all specimens was measured, and one-way ANOVA and Tukey
      Kramer post hoc multiple comparisons tests were performed to identify statistical
      differences between groups. Results: The addition of gold nanoparticles increased
      the flexural strength of acrylic resin. Significantly greater increases were
      obtained with lower concentrations (0.05%) when compared to higher concentrations
      (0.20%). Conclusion: Differences in concentrations of gold nanoparticles added to
      PMMA have significantly different effects on PMMA flexural strength, whereas
      differences in sizes of gold nanoparticles added to PMMA do not significantly
      affect its flexural strength. Accordingly, adding gold nanoparticles to PMMA may
      enhance the mechanical properties of denture bases used in clinical practice.

PMID- 30297563
TI  - Dental anxiety and oral health-related quality of life in children following
      dental rehabilitation under general anesthesia or intravenous sedation: A
      prospective cross-sectional study.
AB  - Purpose: The study aimed to investigate dental anxiety and oral health-related
      quality of life among children undergoing dental rehabilitation under general
      anesthesia (GA) and intravenous sedation (IVS). Materials and Methods:
      Participants were 99 healthy children aged 3-5 or 6-12 years operated under GA or
      IVS. Dental anxiety before treatment and 1 month postoperatively were measured
      using the Frankl behavior scale (FBS), the venham picture test (VPT), the early
      childhood oral health impact scale (ECOHIS), and the children's fear survey
      schedule-dental subscale (CFSS-DS). Data were analyzed using Student's t-test and
      Mann-Whitney U-test. Results: ECOHIS scores decreased in all groups. VPT scores
      increased in the 3-5-year-olds treated under GA (P = 0.003). Postoperative CFSS
      DS anxiety scores were lower in IVS groups. FBS scores were significantly higher
      for both age groups (P < 0.001). There was no effect of numbers of extracted or
      treated teeth. Conclusions: Dental rehabilitation under GA and IVS improved the
      quality of life and dental behavior. In the 6-12-year-olds, there was no
      statistically significant difference between children undergoing dental
      operations under GA and those undergoing dental operations under IVS. Dental
      anxiety decreased in 3-5-year-olds after treatment under GA but not after IVS.

PMID- 30297564
TI  - Efficacy of using erbium, chromium-doped: Yttrium scandium gallium garnet laser
      treated dentine in a dentine barrier test device.
AB  - Objectives: The aim of this study was to evaluate the efficacy of using erbium,
      chromium-doped:yttrium scandium gallium garnet (Er,Cr:YSGG) laser-treated dentine
      in a dentine barrier test device. Materials and Methods: The test materials (G
      BondTM and VitrebondTM) were applied onto laser-treated or laser-untreated
      dentine discs. After 24 h of exposure with perfusion of the test chamber, cell
      survival was evaluated based on enzyme activity and compared to a nontoxic
      control material. The mean of the control was set to 100% viability. Data were
      analyzed using the one-way analysis of variance and the Tukey's honest
      significant difference tests. Results: The responses of bovine pulp-derived cells
      after exposure to G-Bond and Vitrebond on Er,Cr:YSGG laser-treated and laser
      untreated dentin were statistically different from negative control group (P <
      0.05). Conclusion: Er,Cr:YSGG laser treatment was not successful enough in
      decreasing the cytotoxic effects of the dental materials. Different parameters of
      Er,Cr:YSGG laser or different laser types could be investigated as an alternative
      to minimizing the cytotoxic effects of dental materials.

PMID- 30297565
TI  - The effectiveness of erbium: Yttrium-aluminum-garnet laser on enamel
      conditioning: An In vitro study.
AB  - Objectives: The purpose of this in vitro study was to investigate the effect of
      three different enamel surface conditioning procedures on the bonding strength of
      two resin-based filled fissure sealants. Material and Methods: Freshly extracted,
      48 third molar teeth were used in this study. Teeth were randomly divided into
      three main groups as the phosphoric acid etched, erbium: Yttrium-aluminum-garnet
      (ER: YAG) laser etched, and the phosphoric acid plus ER: YAG laser-etched groups.
      The main groups further divided into two subgroups as Clinpro or Fissurit FX
      applied. After preparation of the enamel surfaces and application of the
      sealants, the samples were subjected to shear bond strength test. Results:
      According to statistical analysis with one-way ANOVA, the bonding strength values
      of the phosphoric acid groups were found significantly higher than those values
      obtained from the ER: YAG laser and ER: YAG laser plus phosphoric acid groups (P
      < 0.001). Conclusion: As a result of the study, it has been concluded that the
      laser application alone has no additional benefit to the acid application in
      terms of bonding strength.

PMID- 30297566
TI  - Comparing the interpretation of emergency department computed tomography between
      emergency physicians and attending radiologists: A multicenter study.
AB  - Introduction: Computed tomography (CT) interpretation in the emergency department
      is one of the vital issues that should be carried out rapidly and accurately. The
      objective of this study was to examine the interpretation accuracy of emergency
      physicians (EPs) regarding CT scans at the emergency department for traumatic and
      nontraumatic purposes. Materials and Methods: The study that was carried out as a
      prospective, observational study was completed at four centers during 1 year.
      Results: Accuracy ratios of CT interpretations of EP regarding cranial injuries,
      thoracic injuries and vertebral spine injuries are above 95% in addition to the
      fact that the concordance's with the final result are perfect, the concordance
      with the final results of the CT interpretations of EP for abdominal injuries was
      moderate (<0.75). Accuracy ratios of the CT interpretations of EP for nontrauma
      patients were above 90% for brain hemorrhage and chest injuries and that the
      concordance with the final results was perfect (>=0.75). The CT interpretation
      accuracy rates of EP for spontaneous pneumothorax and aortic aneurysm/aortic
      dissection cases were 100%. CT interpretation rate of EP for pulmonary embolism
      was 89.4%, whereas the level of concordance with the final results was moderate
      (<0.75). Whereas the CT interpretation accuracy rates of EP for nontraumatic
      abdominal injuries varied between 83.3% and 93.1%, their levels of concordance
      with the final results were moderate (<0.75). Conclusions: The CT interpretations
      for abdominal traumatic patients in addition to pulmonary embolism and acute
      nontraumatic abdominal injuries should be carried out more carefully.

PMID- 30297567
TI  - An audit of the diagnosis and reporting of soft tissue sarcomas at the Lagos
      University Teaching Hospital.
AB  - Background: : The effective management of patients with cancer is predicated on
      the right diagnoses and other relevant parameters included in the pathology
      report. This is particularly important in soft tissue pathology where arriving at
      the right diagnosis is often challenging. The aim of this study, therefore, was
      to perform an audit of sarcoma diagnosis and reporting in our institution.
      Methods: Slides of soft tissue sarcomas diagnosed in our institution over a 5
      year period were reviewed with specialist soft tissue pathologists. Ancillary
      immunohistochemistry and fluorescent in situ hybridization were performed where
      necessary. The contents of the reports were assessed using a diagnostic checklist
      developed by the Association of Directors of Anatomic and Surgical Pathology.
      Results: Fifty-five of the 62 patients studied (88.7%) were correctly identified
      as sarcomas. However, the correct diagnoses were made in only 27 patients
      (43.6%). Kaposi sarcoma and dermatofibrosarcoma protuberans were the most
      recognized sarcomas, while leiomyosarcoma, myxofibrosarcoma, and malignant
      peripheral nerve sheath tumor were the least recognized sarcomas. The most
      reported parameters included the histologic type (100%) and size (89.7%), while
      the percentage of necrosis (0%) and the stage (0%) were the least reported
      parameters. Conclusion: A pattern based approach is important for the accurate
      diagnosis of soft tissue sarcomas. Some essential prognostic parameters and
      information needed for management were not included in the histopathology
      reports. The adoption of a structured reporting format and multidisciplinary team
      meetings will help to ensure the inclusion of such important information in the
      pathology report.

PMID- 30297568
TI  - Effects of thoracic epidural or intravenous analgesia on the neutrophil-to
      lymphocyte ratio in thoracotomy cases.
AB  - Background and Purpose: Postoperative pain is a significant problem in
      thoracotomy patients. Our aim in this study was to investigate the relationship
      between postoperative pain and neutrophil-to-lymphocyte ratio (NLR) which is a
      marker of acute inflammatory response. Materials and Methods: Thoracic epidural
      or intravenous analgesia was administered to thoracotomy patients who elected to
      undergo a planned surgery. Patients were divided into two groups according to the
      analgesia method applied postoperatively. Thoracic epidural analgesia was
      recorded as Group 1 and intravenous analgesia as Group 2. Whole blood counts were
      recorded from preoperative and postoperative 24th- and 48th-hour routine blood
      samples, and NLRs were recorded as retrospective file scanning. Postoperative
      24th- and 48th-hour NLRs and preoperative NLR values were recorded. Results:
      Demographic data of the patients included in the study were similar except for
      age. Preoperative NLR was significantly higher in Group 1 at 3.50 (P = 0.004)
      than in Group 2 at 2.51. Postoperative NLRs were similar among both groups.
      Postoperative NLR values at both the 24th- and 48th-hour increased by4.9 times in
      Group 1 and 9.23 times in Group 2 from the 24th-hour preoperative period, when
      the preoperative NLRs were evaluated. The rate of increase in Group 1 was
      significantly lower than in Group 2 (P = 0.006). Conclusion: Postoperative NLR
      alterations when compared with preoperative values were related to the analgesic
      regimen used.

PMID- 30297569
TI  - Impact of cowpea fortified cookies on anthropometric and micronutrient status of
      primary school children: A randomized, single-blind controlled trial.
AB  - Background: Micronutrient deficiencies are public health problems among school
      children. Food-to-food fortification may reduce the prevalence of these
      deficiencies. Aim: To assess the impact of cowpea (Vigna sinensis) fortified
      cookies on weight, height, body mass index (BMI), hemoglobin, serum vitamin A,
      and zinc status of primary school children aged 6-12 years. Methods: A randomized
      single-blind controlled trial was conducted for 4 weeks among 17 pupils who were
      voluntarily recruited and randomly assigned to experimental (Group A) and control
      (Group B) groups. Group A was fed wheat cookies incorporated with cowpea in a
      ratio of 60:40, while Group B received 100% wheat cookies. Data were collected
      through questionnaire, anthropometry, and biochemical analysis. Statistical
      analysis involved descriptive statistics and t-test. Significance was set at P <
      0.05. Results: The study involved 17 school children out of which 10 (58.8%) were
      boys and 7 (41.2%) were girls; 12 (70.6%) were 10-12 years old and 4 (23.5%) were
      in lower primary (1-3). Group A had increases in hemoglobin (15.5%), serum
      ferritin (28.3%), serum zinc (38.9%), weight (3.0%), BMI (3.4%), and serum
      vitamin A (26.3%); only increases in hemoglobin, serum ferritin, and vitamin A
      attained significance (P < 0.05). Though there was increase in weight (6.1%), BMI
      (5.4%), hemoglobin (5.0%), serum ferritin (16.4%), zinc (20.8%), and vitamin A
      (17.5%) of Group B, these increases were not significant (P > 0.05). Group A had
      significantly (P < 0.05) higher serum ferritin (51.3 MUg/L) than Group B (44.7
      MUg/L). Conclusion: Consumption of cowpea fortified cookies had significant
      positive effects on hemoglobin, serum ferritin, and vitamin A levels of school
      children and should be encouraged at household and industrial levels.

PMID- 30297570
TI  - Severe falciparum malaria in children in Enugu, South East Nigeria.
AB  - Introduction: Severe malaria remains one of the leading causes of morbidity and
      mortality in sub-Saharan Africa and parts of Asia despite several efforts in
      prevention and management. The prevalence and pattern of presentation may vary
      from one location to another and from one age group to another. Objectives: This
      study was undertaken to review the prevalence and pattern of severe malaria among
      children presenting in the two tertiary hospitals in Enugu, south-east Nigeria.
      Methods: The case records of children presenting with malaria in the two tertiary
      hospitals in the state were retrieved and the necessary information were obtained
      using a structured questionnaire. Results: The children aged from 1 month to 184
      months (15 years), with a median age of 36 months and mean age of 49.2 +/- 42.7
      months. About two-thirds (68/102, 66.7%) of the children were under the age of 5
      years, with only 6 of them (8.8%) being 6 months and below. There were
      significantly more males than females (chi2 = 6.48, P = 0.01); with a M:F ratio
      of 1.55:1. The peak of presentation was from August and November. Prostration,
      respiratory distress and severe anaemia were the commonest features of severe
      malaria, while shock, acute renal failure and abnormal bleeding were the least
      presenting features Of all the features, only severe anaemia was significantly
      related to age, (chi2 = 5.027, P = 0.02). Sixty-one (59.8%) of the children had
      one or more co-morbidities. There were 2 deaths, giving a case fatality rate of
      1.96%. Conclusion: Early presentation will significantly reduce blood
      transfusions, prolonged admission and death in children with severe malaria.

PMID- 30297571
TI  - The effect of gender differences in protracted hiccups.
AB  - Background: Although little importance is attached to hiccups, they may be
      associated with several diseases. The purpose of this study was to investigate
      the effects of gender differences on types of hiccups and the relation with
      diseases involved in the etiology. Materials and Methods: Patients presenting to
      the Kirikkale University Medical Faculty Hospital with hiccups were investigated
      retrospectively. Patients' age, sex, duration of hiccups, additional diseases,
      advanced imaging results, laboratory tests, and clinical follow-up were recorded.
      Patients were divided into two groups; Group transient hiccup (TH) consisted of
      subjects with a duration of hiccups less than 48 h, and Group protracted hiccup
      (PH) of patients with a duration exceeding 48 h. The Chi-square test was used for
      comparisons, and P < 0.05 were regarded as significant. Results: Eighty-four
      patients were enrolled, 44.1% (n = 37) in Group TH, and 55.9% (n = 47) in Group
      PH. Male patients comprised 67.5% (n =25) of Group TH and 89.4% (n = 42) of Group
      PH (P = 0.027). The conditions most associated with hiccups were gastrointestinal
      system (GIS) diseases. Correlation was determined between GIS diseases and male
      gender (P = 0.034), no relation between other system diseases and gender.
      Correlation was determined between GIS diseases and protracted hiccups (P =
      0.037), but no relation between other system diseases and type of hiccups.
      Conclusion: Protracted hiccups are more common in males. This gender variation
      applies particularly to hiccups of GIS origin.

PMID- 30297572
TI  - Cancer-testis antigen GAGE-1 expression and serum immunoreactivity in
      hepatocellular carcinoma.
AB  - Aim: To explore the use of cancer-testis antigen G antigen 1 (GAGE-1) in the
      diagnosis and potential therapeutic targeting of hepatocellular carcinoma (HCC),
      we measured the expression of GAGE-1 protein levels in HCC tissues and its serum
      immunoreactivity in HCC patients. Materials and Methods: We detected the
      expression of GAGE-1 protein in HCC by immunohistochemistry (IHC). We then
      analyzed the clinical significance of GAGE-1 expression in HCC with respect to
      clinicopathological parameters. We observed positive anti-GAGE-1 antibody
      reactivity in HCC patient serum, liver cirrhosis patients (LC), hepatitis B
      patients (HB), and normal human individuals (NHS) by enzyme-linked immunosorbent
      assay. Results: The IHC results showed that the positive rates of GAGE-1 protein
      expression in cancer tissues and adjacent tissues were 43.3% (26/60) and 5%
      (3/60), respectively. The expression level of GAGE-1 protein in HCC tissues was
      significantly higher than that in tumor-adjacent tissues (P < 0.05). Positive
      GAGE-1 protein expression was not correlated with clinicopathological parameters
      (P > 0.05). Positive serum anti-GAGE-1 antibody reactivity in HCC patients, LC,
      HB, and NHS was 23.33% (14/59), 13.1% (8/61), 3.3% (2/60), and 3.4% (2/59),
      respectively. The frequency of anti-GAGE-1 antibody-positive sera in HCC patients
      and LC was significantly different than that in HB and NHS (P < 0.01), but no
      significant differences were found between HCC patients and LC (P = 0.485) or
      between HB and NHS (P = 0.410). Positive anti-GAGE-1 antibody reactivity was not
      correlated with clinicopathological parameters (P > 0.05). Conclusion: These data
      illustrate that the GAGE-1 protein exhibits moderate cancer-restricted pattern of
      expression and immunogenicity, laying the foundation for the application of GAGE
      1 in immunotherapy and for the diagnosis of HCC.

PMID- 30297573
TI  - A community-based surveillance of gastrointestinal helminthiasis among pregnant
      women in Ibadan, South West Nigeria.
AB  - Background: : Intestinal helminthiasis is a major public health problem in
      Africa. Helminthic infection in pregnant women causes loss of appetite, poor
      nutrient absorption, gastrointestinal impairment, iron deficiency, and iron
      deficiency anemia resulting in low birth weights and preterm births. The main aim
      of this study is to assess the prevalence of helminthic infections in pregnant
      women in rural and peri-urban communities of Ibadan. Materials and Methods: : A
      cross-sectional descriptive study was carried out at the antenatal clinics of 12
      selected primary health centers and mission homes in Ibadan, Nigeria. Open- and
      closed-answer questionnaires were administered to 604 consenting pregnant women,
      who provided fresh stool samples for microscopy. Helminthic quantification was
      carried out by the Kato-Katz technique. Proportions were compared using Chi
      squared with IBM(r) SPSS(r) Statistics 21 for analysis. Statistical significance
      was set at P < 0.05. Results: : Eighty-nine stool samples (14.7%) were positive
      for helminthiasis. Most had roundworms (13.6%); 13 (2.2%) had hookworms. The mean
      arithmetic eggs per gram of feces were 2,124 and 248, respectively. No
      participant had a heavy intensity infection; nearly all were of low intensity.
      Participants (P = 0.005) and their husbands (P = 0.005) who had higher education
      were less likely to have helminthiasis. Conclusion: These communities are
      classified as Category III, having a low prevalence and low intensity infection.
      Therefore, prophylactic anti-helminthic treatment in pregnancy is not
      recommended. The inverse relationship with education may be a function of better
      living conditions. Better hygiene should be advocated.

PMID- 30297574
TI  - Intrauterine insemination in ovulatory infertile patients.
AB  - Aim: Although there are many studies in literature comparing intrauterine
      insemination (IUI) and timed intercourse, there are only a few studies examining
      the use of clomiphene citrate (CC) in ovulatory infertile patients. The aim of
      this study was to compare IUI following CC-induced ovulation and timed
      intercourse following CC-induced ovulation in ovulatory infertile patients.
      Methods: Hundred patients who had IUI or timed intercourse following ovulation
      induction (OI) via CC between 2012 and 2014 are prospectively scanned. Both
      groups were consisted of 50 patients. Both in groups 1 and 2 patients, the
      treatment with clomiphene citrate was started on the 3rd day of the menstrual
      cycle with a dose of 50 mg/day and was continued for 5 consecutive days. On the
      13th day of the cycle, the patients were called for examination and
      folliculometry tests were performed via transvaginal ultrasonography. Human
      chorionic gonadotropin (HCG, a prepared syringe containing 250 MUg/0.5 ml [6,500
      IU equivalent] choriogonadotropin alpha) was given to all patients with a
      sufficient size follicle (18-20 mm). Group 1 patients were recommended to have
      coitus regularly for a week after the HCG treatment. In group 2, IUI was
      performed 36 h after the HCG treatment. Results: Clinical pregnancy was provided
      in 28 patients in 100 patients. In group 1, the pregnancy rate per person was 6%,
      the pregnancy rate per cycle was 2.3%, and live birth rate was 6%. In group 2,
      the pregnancy rate per person was 22%, the pregnancy rate per cycle was 8.3%, and
      live birth rate was 23%. A statistically significant difference was observed
      between groups 1 and 2 in terms of pregnancy per person rate, pregnancy per cycle
      rate, and live birth rate. Conclusion: In the patients who had OI via CC, the
      pregnancy rates obtained with IUI were statistically significantly higher than
      timed intercourse.

PMID- 30297575
TI  - Benefits of anticitrullinated peptides examination in rheumatoid arthritis.
AB  - Background: Anti-citrullinated peptides antibodies (ACPA) are specific for
      rheumatoid arthritis and have been implicated in disease pathogenesis. ACPA
      examination is a new component of ACR/EULAR 2010 classification criteria for
      rheumatoid arthritis. ACPA positivity predicts a more erosive disease course with
      severe joint damage and extra-articular manifestations. Objectives: To evaluate
      the benefits of ACPA examination in patients with early undifferentiated
      arthritis and patients with rheumatoid arthritis. Methods: We examined patients
      with arthritis and tested them for ACPA positivity. In every individual patient
      we evaluated if ACPA examination was necessary to establish the diagnosis of
      rheumatoid arthritis, or to change treatment, or if the diagnosis could have been
      established without ACPA examination (ACR/EULAR 2010 classification criteria was
      met without ACPA scoring). Results and Conclusions: The study was placed in
      Slovak Republic. We examined 833 patients with arthritis. There were 43 patients,
      or 62% of a subgroup of 69 who were ACPA positive whose ACPA examination was not
      needed-ACR/EULAR criteria was met without ACPA scoring. This number represents
      5.1% of the total number examined. There were 15 patients, or 22% of the subgroup
      and 1.8% of the total whose diagnosis was revised to rheumatoid arthritis due to
      ACPA positivity-ACR/EULAR criteria were met solely with ACPA scoring. There were
      11 patients (16% and 1.3%) whose medication was changed due to ACPA positivity.
      ACPA examination is useful in 3.1% of all examined patients. When we correlate
      data on ACPA positive patients, 38% of the patients profit from ACPA
      examinations. Considering the relatively low price of ACPA testing, this
      examination should not be excluded.

PMID- 30297576
TI  - Metastatic squamous cell cancer with unknown primary origin in the mediastinal
      lymph node.
AB  - Metastatic tumors with unknown primary origin are a group of heterogeneous tumors
      with undetectable primary tumor site on admission. They have the common
      properties of rapid and aggressive progression and unpredictable metastases. They
      form 3%-5% of all cases with cancer and the fourth-most common cause of cancer
      related deaths. The histological type of these tumors is commonly (90%)
      adenocarcinoma, whereas 5% are squamous cell carcinomas. Metastasis is observed
      in the liver, lungs, and bones. Mediastinal lymph node metastasis is extremely
      rare. They have a poor prognosis and the mean survival is shorter than a year.
      The case we have presented is a rare case due to its mediastinal lymph node
      involvement among tumors with unknown origin and squamous cell histological
      subtype.

PMID- 30297577
TI  - Crohn's disease with positive Ziehl-Neelsen stain: Three case reports.
AB  - Because of the similarity of the clinical symptoms, endoscopic, and pathological
      features, the differential diagnosis between Crohn's disease (CD) and intestinal
      tuberculosis (ITB) remains difficult, especially in a high-incidence area of
      tuberculosis (TB). Here we reported three patients with positive Ziehl-Neelsen
      stain in endoscopic mucosal biopsy specimens. They had a poor response to anti-TB
      therapy but a good response to immunosuppresses, infliximab, or surgery, and were
      finally diagnosed as CD. It was not clear that they were CD concomitant with
      mycobacteria infection or CD induced by mycobacteria infection. Further studies
      including more clinical cases and related animal models are needed. Our cases
      highlight the importance of considering the presence of CD in patients with
      positive Ziehl-Neelsen stain, which were failure to respond to anti-TB treatment.

PMID- 30297578
TI  - Time-dependent cervical vagus nerve stimulation and frequency-dependent right
      atrial pacing mediates induction of atrial fibrillation.
AB  - OBJECTIVE: This study aimed to investigate the effects of right cervical vagus
      trunk simulation (RVTS) and/or right atrial pacing (RAP) on the induction of
      atrial fibrillation (AF). METHODS: Twenty-four healthy adult dogs were randomly
      divided into four groups: RAP groups comprising RAP500 (RAP with 500 beats/min)
      and RAP1000 (RAP with 1000 beats/min) and RVTS groups comprising RVTS and
      RAP500+RVTS. All dogs underwent 12-h intermittent RAP and/or RVTS once every 2 h.
      The AF induction rate, AF duration, atrial effective refractory period (ERP), and
      dispersion of ERP (dERP) were compared after every 2 h of RAP or/and RVTS.
      RESULTS: All groups had successful AF induction. The RAP1000 group had the
      highest AF induction rate and the longest AF duration. The RAP1000 group also had
      a shortened ERP in comparison to the other groups as well as the maximum dERP.
      Compared to the RAP500 group, RAP500+RVTS had an increased capacity to induce AF
      as measured by the AF induction rates, AF duration, ERP, and dERP. CONCLUSION:
      Increased tension in the vagus nerve and the intrinsic cardiac autonomic nervous
      system plays an important role in AF induction through different potential
      mechanisms. Interventions involving the vagus nerve and/or intrinsic cardiac
      autonomic nervous system can be a future potential therapy for AF.

PMID- 30297579
TI  - Evaluation of the effect of non-ergot dopamine agonists on left ventricular
      systolic function with speckle tracking echocardiography.
AB  - OBJECTIVE: Parkinson's disease (PD) is a neurological disorder, and ergot
      dopamine agonists (DAs) are no longer usually preferred in the treatment due to
      the increased risk of valvular heart disease. Some recent studies have shown that
      commonly used non-ergot DA also increases the risk of heart failure. On the other
      hand, there are studies showing conflicting data about this relationship. The aim
      of the present study was to investigate the cardiac effects of non-ergot DAs in
      patients with PD using echocardiography. METHODS: Conventional echocardiography
      and two-dimensional (2D) speckle tracking strain echocardiography were performed
      to determine the possible systolic dysfunction prior to the development of
      apparent systolic heart failure. Ninety-one (55 male, 64+/-10 years) patients
      with PD were included in the study. Furthermore, 25 subjects with newly diagnosed
      PD and using no drug were enrolled as the control group. All patients were
      divided into groups according to their medication. Patients using levodopa were
      classified as Group 1 (36), levodopa+pramipexole as Group 2 (27), and
      levodopa+ropinirole as Group 3 (28). RESULTS: Left ventricle dysfunction with non
      ergot DA use in patients with PD was not established with conventional
      echocardiographic evaluation. For 2D strain analysis, global longitudinal strain
      values were obtained as -18.5%, -18.5%, and -18.9% in the groups, respectively.
      Strain and strain rate values of the left ventricle were not different between
      the groups (p=0.816 and p=0.881, respectively). CONCLUSION: There was no
      significant relationship between left ventricular dysfunction and use of non
      ergot DA in patients with PD. Similar results were obtained in strain analysis
      showing left ventricular subclinical dysfunction. Our study appears to confirm
      the safety of non-ergot DA in the point of heart failure risk. To our knowledge,
      this is the first study to evaluate the effect of this group of drugs on
      subclinical left ventricular systolic function.

PMID- 30297580
TI  - Role of microcirculatory function and plasma biomarkers in determining the
      development of cardiovascular adverse events in patients with peripheral arterial
      disease: A 5-year follow-up.
AB  - OBJECTIVE: The aim of this long-term follow-up study was to investigate the
      association of local and systemic cardiovascular complications with endothelium
      dependent and-independent microvascular relaxations and blood biomarkers and
      biochemicals in patients with peripheral arterial disease (PAD) caused by
      atherosclerosis. METHODS: This prospective study included 67 patients with PAD
      who had not undergone any endovascular intervention, peripheral arterial surgery,
      or major amputation. Changes in the microvascular blood flow were measured using
      laser Doppler imaging after iontophoresis of acetylcholine (ACh) and sodium
      nitroprusside (SNP). The biochemical markers of high sensitivity C reactive
      protein (hs-CRP), nitric oxide (NO), total antioxidant capacity (TAC), asymmetric
      dimethyl arginine (ADMA), and hydrogen sulfide (H2S) levels were measured from
      blood samples. All the patients were followed up for 5 years to determine the
      development of cardiovascular adverse events (CVAEs) and major amputation. At the
      end of the follow-up period, the patients were classified into two groups: those
      who had a CVAE [CVAE (+)] and those who did not experience CVAE [CVAE (-)].
      Parameters such as demographic features, atherosclerotic risk factors, chronic
      ischemia category, microvascular endothelial functions, and plasma biomarkers
      were compared between the groups. RESULTS: A total of 67 patients comprising 61
      (91%) males and 6 (9%) females with a mean age of 62.3+/-9.7 years were included.
      During the follow-up period, 29 patients had CVAE (43.3%) and 38 patients did not
      have CVAE (56.7%). There was no difference between the groups in terms of ACh and
      SNP-induced vasodilation responses. Plasma high density lipoprotein (HDL)
      cholesterol values were lower in the CVAE (+) group [(CVAE+HDL: 38.4+/-9.1),
      (CVAE-HDL: 44.7+/-11.1), p=0.02]. Plasma hs-CRP values were significantly higher
      in the CVAE (+) group [(CVAE+ hs-CRP: 14.3+/-20.6), (CVAE-hs-CRP: 5.9+/-10.9),
      p=0.004]. No significant difference was observed between the groups in terms of
      plasma biomarkers and other biochemical levels. CONCLUSION: Based on the study
      findings, it was concluded that only low plasma HDL and high hs-CRP levels were
      risk factors for the development of CVAEs during follow-up of patients with PAD.

PMID- 30297581
TI  - Long-term outcomes in patients who underwent surgical correction for
      atrioventricular septal defect.
AB  - OBJECTIVE: The follow-up results of patients operated for atrioventricular septal
      defect (AVSD) during 1996-2016 at Baskent University are presented. METHODS: Data
      obtained from hospital records consists of preoperative echocardiographic and
      angiographic details, age and weight at surgery, operative details, Down syndrome
      presence, postoperative care details, early postoperative and latest
      echocardiographic findings and hospitalization for reintervention. RESULTS: A
      total of 496 patient-files were reviewed including 314 patients (63.4%) with
      complete and 181 (36.6%) with partial AVSD (48.4% of all patients had Down
      syndrome). Atrioventricular (AV) valve morphology was Rastelli type A in 92.2%, B
      in 6.5%, and C in 1.3% of patients. The operative technique used was single-patch
      in 21.6% (108), double-patch in 25.8% (128), and modified single-patch (Wilcox)
      in 52.5% (260) of patients. The follow-up time was 37.79+/-46.70 (range, 0-198)
      months. A total of 64 patients (12.9%) had arrhythmias while in the intensive
      care unit; pacemaker was implanted in 12 patients. A total of 78 patients (15.7%)
      were treated for pulmonary hypertensive crisis. The early morbidity and mortality
      in the postoperative first month were calculated as 38% and 10%, and the late
      morbidity and mortality (>1 month) were calculated as 13.1% and 1.9%,
      respectively. The rate of reoperation in our cohort was 8.9%. CONCLUSION:
      Although the early morbidity and mortality are low in AVSD operations, the rate
      of reoperations for left AV valve insufficiency are still high. Although Down
      syndrome is not a risk factor for early mortality, the co-morbid factors, such as
      longer postoperative mechanical ventilator or inotropic support, lead to higher
      risk for morbidity. The frequency of pulmonary hypertension and consequent
      complications are also high.

PMID- 30297582
TI  - Modeling the burden of cardiovascular disease in Turkey.
AB  - OBJECTIVE: This study aims to estimate the current and future burden of
      cardiovascular diseases (CVD) in Turkey. METHODS: A burden-of-disease model was
      developed that included inputs on population growth, prevalence, and incidence of
      ischemic disease (IHD) and cerebrovascular disease (CeVD), prevalence of
      modifiable risk factors, mortality rates, and relationship between risk factors
      and IHD/CeVD. Direct costs to the public health-care system and indirect costs
      from lost production due to premature mortality, hospitalizations, disability,
      and absenteeism were considered. RESULTS: We estimated that in 2016, 3.4 million
      Turkish adults were living with CVD, including 2.5 million affected by IHD, and
      0.9 million by CeVD. This prevalence is projected to increase to 5.4 million by
      2035. The economic burden of CVD was estimated at US$10.2 billion in 2016,
      projected to increase twofold to US$19.4 billion by 2035. CONCLUSION: Our study
      confirms that the current burden of CVD is significant, and that it is projected
      to increase at a steep rate over the next two decades. This growing burden of
      disease will likely create significant pressure on the public health-care system
      in the form of direct health-care costs, as well as on society in the form of
      lost productivity.

PMID- 30297583
TI  - Tips for management of arrhythmias in endocrine disorders from an European Heart
      Rhythm Association position paper.
AB  - In endocrine diseases, hormonal changes, electrolyte abnormalities, and the
      deterioration of heart structure can lead to various arrhythmias. In diabetic
      patients, hypoglycemia, hyperglycemia, and hypokalemia can trigger arrhythmias,
      and diabetic cardiomyopathy can also cause electrical and structural remodeling
      to form substrates for arrhythmias. The risk of atrial fibrillation (AF)
      increases in hyperthyroidism; however, the prevalence of ventricular arrhythmias
      in hypothyroidism is higher. Besides AF and ventricular tachycardias,
      bradycardias and atrioventricular blocks can also be seen in pheochromocytoma due
      to the desensitization of adrenergic cardiovascular receptors. The correction of
      metabolic and electrolyte disturbances in patients with adrenal cortex disease
      should be the main approach in the prevention and treatment of arrhythmias. Early
      initiation of treatment in patients with acromegaly seems to decrease the
      development of cardiac remodeling and ventricular arrhythmia. Early and late
      after depolarizations due to hypercalcemia in hyperparathyroidism can lead to
      life-threatening ventricular arrhythmias. This elegant position paper provides
      important recommendations regarding prevention and treatment of arrhythmias for
      specific endocrine disorders.

PMID- 30297584
TI  - Intravascular leiomyoma with intracardiac extension associated with hepatorenal
      polycystic disease.

PMID- 30297585
TI  - Biventricular non-compaction cardiomyopathy with pulmonary stenosis, interatrial
      septal aneurysm, atrial septal defect, bradycardia, and mental retardation in a
      single case: A case report.

PMID- 30297586
TI  - Strain can hide some states.

PMID- 30297588
TI  - Bizarre ST elevation.

PMID- 30297587
TI  - Author's Reply.

PMID- 30297589
TI  - Author's Reply.

PMID- 30297590
TI  - Does the country of origin matter for finding research internships in the United
      States?

PMID- 30297591
TI  - Evaluation of renal dysfunction after ST-elevation myocardial infarction.

PMID- 30297592
TI  - Author's Reply.

PMID- 30297593
TI  - Ruptured aortic dissection into the pulmonary artery: A case study.

PMID- 30297594
TI  - Interventricular septal dissection sustained by an aneurysmal sac.

PMID- 30297595
TI  - Long-term results of some interesting studies and more....

PMID- 30297596
TI  - microRNA-29a inhibits cardiac fibrosis in Sprague-Dawley rats by downregulating
      the expression of DNMT3A.
AB  - OBJECTIVE: This study aims to investigate the effect of miR-29a targeting the
      regulation of DNMT3A on the development of cardiac fibrosis in Sprague-Dawley
      (SD) rats. METHODS: In vivo experiment: SD rats were randomly divided into model
      and control groups. The cardiac and left ventricular indices in each group were
      calculated. The pathological changes of the myocardium were observed. The
      expression levels of miR-29a, CollA1, alpha-SMA, and DNMT3A in the myocardium of
      each group were detected. In vitro experiment: The cardiac fibroblasts (CFs) of
      SD rats were isolated from the myocardial tissue of SD rats and cultured. The miR
      29a mimics, inhibitors, DNMT3A-siRNA, and control-siRNA were transfected into
      CFs. The expression levels of miR-29a, DNMT3A, CollA1, and alpha-SMA were
      detected, and the proliferation of CFs after transfection was observed. RESULTS:
      The heart weight index of the rats in the model group increased significantly
      compared with that in the control group. Obvious collagen deposition was observed
      in the myocardial tissue of the model group. The expression levels of CollA1,
      alpha-SMA, and DNMT3A in the model group were significantly higher than those in
      the control group (p<0.05). CONCLUSION: miR-29a reduced the activation and
      proliferation of CFs to improve cardiac fibrosis probably by the downregulation
      of DNMT3A.

PMID- 30297597
TI  - Predictive value of baseline C-reactive protein for periprocedural myocardial
      infraction of higher risk stratifications: A retrospective cohort clinical study.
AB  - OBJECTIVE: It is controversial whether preprocedural elevated high sensitivity C
      reactive protein (CRP) could increase the incidence of periprocedural myocardial
      infraction (PMI) of higher risk stratifications. The primary aim of this study
      was to evaluate whether preoperative elevated CRP level was related to the
      incidence of PMI in patients who underwent percutaneous coronary intervention
      (PCI). METHODS: A total of 4,426 patients [66 y (59, 75); 72.3% males] with
      normal preprocedural cardiac enzymes were prospectively divided into two groups;
      the elevated CRP group was defined as CRP >3 mg/L, which was approximately 30.4%
      of the patients. The relationship between CRP and the incidence of PMI was
      established by multivariate logistic regression analysis, and multivariate linear
      regression analysis was used to assess the correlation between CRP and the
      severity of myocardial injury. RESULTS: The incidence rates were similar between
      the two groups with periprocedural myocardial minor necrosis (34.23% versus
      32.74%, p=0.607), but significantly differed based on the 2007 (defined as
      cardiac enzymes >3-fold elevations), 31.25% in high CRP group versus 26.25% in
      low group [odds ratio (OR) 1.19; p=0.046] and the 2012 universal PMI (defined as
      cardiac enzymes >5-fold elevations with at least one clinical evidence, such as
      chest pain, ECG changes or imaging diagnosis of heart ischemia), 19.79% versus
      15.35% (OR 1.26, p=0.023); besides, the PMI ratios increased in line with the
      elevation of CRP (p=0.006 for the 2007 and p=0.011 for the 2012 universal PMI).
      However, no significant linear relationship was found between CRP and high
      sensitivity cardiac troponin I peak post-PCI. CONCLUSION: Elevated baseline CRP
      was an independent risk factor for the incidence of the 2007 and the 2012
      universal PMI rather than minor necrosis. However, CRP may not correlate with the
      severity of minor myocardial necrosis in patients with PMI.

PMID- 30297598
TI  - Do Individuals in Old Age Prepare for the Risk of Long-Term Care? Results of A
      Population-Based Survey in Germany.
AB  - The aim of the present study was to identify specific actions and financial
      precautions undertaken by individuals in preparation for their long-term care
      needs, as well as to determine the correlates of these actions. A population
      based survey of the German population aged 65 years and above (n = 1006) was
      used. Individuals were asked whether they have undertaken financial preparations
      for their long-term care needs (no; yes). With respect to specific actions,
      individuals were asked whether they (no; yes): (i) Had obtained information
      (e.g., from doctor, internet, care support center, care facility), (ii) had
      modified their home (e.g., installed a stair lift), and (iii) had moved (e.g.,
      old-age housing, care in relatives' homes). In total, 30.4% had undertaken
      financial preparations for their long-term care needs. With respect to the
      specific actions undertaken, 6.5% had obtained information, 4.8% modified their
      home, and 7.3% had moved. The outcome measure, 'had modified home', was
      positively associated with lower age, West Germany, and lower self-rated health.
      The outcome measure, 'had moved', was positively associated with being female,
      and higher education. The outcome measure, 'financial preparations for long-term
      care needs', was positively associated with lower age, West Germany, higher
      education, being born in Germany, and private health insurance. It is alarming
      that only around one in three individuals aged 65 and older had undertaken
      financial preparations for long-term care needs, and that far fewer individuals
      had undertaken other actions to prepare for their long-term care needs. The
      provision of timely information regarding the risk of long-term care, as well as
      its associated costs, may assist in sustaining the satisfaction of long-term care
      recipients. It may also help to reduce the risk of long-term care for individuals
      in old age.

PMID- 30297599
TI  - The Identification of the Factors Related to Household Food Insecurity among
      Indigenous People (Orang Asli) in Peninsular Malaysia under Traditional Food
      Systems.
AB  - Over the course of 16 years, a high percentage of Orang Asli (OA) households in
      Malaysia has been found to be burdened with food insecurity. Therefore, a study
      was conducted to improve the understanding of the challenges faced by the OA in
      Peninsular Malaysia to achieve food security under traditional food systems. In
      this study, in-depth interview sessions, which were assisted by an interview
      protocol, were conducted with 61 OA women from nine villages that were selected
      purposefully across three states (Kelantan, Pahang, and Perak) in Peninsular
      Malaysia. Furthermore, thematic analysis was performed during data analysis. As a
      result, four themes were identified, namely (i) the failure in agriculture (sub
      themes: threats from wild animals and insufficient land supply), (ii)
      ineffectiveness of traditional food-seeking activities (sub-themes: exhausting,
      tiring, dangerous, and time-consuming journey for food-seeking activities,
      depletion of natural commodities, reduced demands of natural commodities, and
      lack of equipment), (iii) weather (sub-themes: rainy and dry seasons), and (iv)
      water issues (subthemes: continuity of water supply and cleanliness of water).
      The identified modifiable factors of this issue should be incorporated into
      future schemes of food security intervention in order to efficiently manage the
      food shortage among the OA.

PMID- 30297601
TI  - A Novel Wind Speed Estimation Based on the Integration of an Artificial Neural
      Network and a Particle Filter Using BeiDou GEO Reflectometry.
AB  - Oceanographic remote sensing, which is based on the sensitivity of reflected
      signals from the Global Navigation Satellite Systems (GNSS), so-called GNSS
      Reflectometry (GNSS-R), is very useful for the observation of ocean wind speed.
      Wind speed estimation over the ocean is the core factor in maritime
      transportation management and the study of climate change. The main concept of
      the GNSS-R technique is using the different times between the reflected and the
      direct signals to measure the wind speed and wind direction. Accordingly, this
      research proposes a novel technique for wind speed estimation involving the
      integration of an artificial neural network and the particle filter based on a
      theoretical model. Moreover, particle swarm optimization was applied to find the
      optimal weight and bias of the artificial neural network, in order to improve the
      accuracy of the estimation result. The observation dataset of the reflected
      signal information from BeiDou Geostationary Earth Orbit (GEO) satellite number 4
      was used as an input for the estimation model. The data consisted of two phases
      with I and Q components. Two periods of BeiDou data were selected, the first
      period was from 3 to 8 August 2013 and the second period was from 12 to 14 August
      2013, which corresponded to events from the typhoon Utor. The in situ wind speed
      measurement collected from the buoy station was used to validate the results. A
      coastal experiment was conducted at the Yangjiang site located in the South China
      Sea. The results show the ability of the proposed technique to estimate wind
      speed with a root mean square error of approximately 1.9 m/s.

PMID- 30297600
TI  - Zinc Inhibits Expression of Androgen Receptor to Suppress Growth of Prostate
      Cancer Cells.
AB  - The prostate gland contains a high level of intracellular zinc, which is
      dramatically diminished during prostate cancer (PCa) development. Owing to the
      unclear role of zinc in this process, therapeutic applications using zinc are
      limited. This study aimed to clarify the role of zinc and its underlying
      mechanism in the growth of PCa. ZnCl2 suppressed the proliferation of androgen
      receptor (AR)-retaining PCa cells, whereas it did not affect AR-deficient PCa
      cells. In LNCaP and TRAMP-C2 cells, zinc downregulated the expression of AR in a
      dose- and time-dependent fashion. Zinc-mediated AR suppression accordingly
      inhibited the androgen-mediated transactivation and expression of the androgen
      target, prostate specific antigen (PSA). This phenomenon resulted from
      facilitated protein degradation, not transcriptional control. In studies using
      mice bearing TRAMP-C2 subcutaneous tumors, the intraperitoneal injection of zinc
      significantly reduced tumor size. Analyses of both xenograft tumors and normal
      prostates showed reduced expression of AR and increased cell death. Considering
      the significant loss of intracellular zinc and the dominant growth-modulating
      role of AR during PCa development, loss of zinc may be a critical step in the
      transformation of normal cells to cancer cells. This study provides the
      underlying mechanism by which zinc functions as a PCa suppressor, and forms the
      foundation for developing zinc-mediated therapeutics for PCa.

PMID- 30297602
TI  - Validation of a Novel Modified Aptamer-Based Array Proteomic Platform in Patients
      with End-Stage Renal Disease.
AB  - End stage renal disease (ESRD) is characterized by complex metabolic
      abnormalities, yet the clinical relevance of specific biomarkers remains unclear.
      The development of multiplex diagnostic platforms is creating opportunities to
      develop novel diagnostic and therapeutic approaches. SOMAscan is an innovative
      multiplex proteomic platform which can measure >1300 proteins. In the present
      study, we performed SOMAscan analysis of plasma samples and validated the
      measurements by comparison with selected biomarkers. We compared concentrations
      of SOMAscan-measured prostate specific antigen (PSA) between males and females,
      and validated SOMAscan concentrations of fibroblast growth factor 23 (FGF23), FGF
      receptor 1 (FGFR1), and FGFR4 using Enzyme-Linked immunosorbent assay (ELISA).
      The median (25th and 75th percentile) SOMAscan PSA level in males and females was
      4304.7 (1815.4 to 7259.5) and 547.8 (521.8 to 993.4) relative fluorescence units
      (p = 0.002), respectively, suggesting biological plausibility. Pearson
      correlation between SOMAscan and ELISA was high for FGF23 (R = 0.95, p < 0.001)
      and FGFR4 (R = 0.69, p < 0.001), indicating significant positive correlation,
      while a weak correlation was found for FGFR1 (R = 0.13, p = 0.16). In conclusion,
      there is a good to near-perfect correlation between SOMAscan and standard
      immunoassays for FGF23 and FGFR4, but not for FGFR1. This technology may be
      useful to simultaneously measure a large number of plasma proteins in ESRD, and
      identify clinically important prognostic markers to predict outcomes.

PMID- 30297603
TI  - Zoonotic Helminth Diseases in Dogs and Dingoes Utilising Shared Resources in an
      Australian Aboriginal Community.
AB  - The impacts of free-roaming canids (domestic and wild) on public health have long
      been a concern in Australian Indigenous communities. We investigated the
      prevalence of zoonotic helminth diseases in dogs and sympatric dingoes, and used
      radio telemetry to measure their spatial overlap, in an Aboriginal community in
      the Wet Tropics of Australia. Samples collected from dingoes and dogs showed high
      levels of infection with the zoonotic hookworm, Ancylostoma caninum. Dingoes were
      also positive for A. ceylanicum infection (11.4%), but dogs were infection free.
      Whipworm, Trichuris vulpis, infection was far more prevalent in necropsies of
      domestic dogs (78.6%) than dingoes (3.7%). Dogs were free from Dirofilaria
      immitis infection, while dingoes recorded 46.2% infection. Eleven dingoes and
      seven free-roaming domestic dogs were fitted with Global Positioning System
      collars and tracked over an extended period. Dingo home-ranges almost completely
      overlapped those of the domestic dogs. However, dingoes and dogs did not utilise
      the same area at the same time, and dogs may have avoided dingoes. This spatial
      overlap in resource use presents an opportunity for the indirect spill-over and
      spill-back of parasites between dogs and dingoes. Tracking and camera traps
      showed that the community rubbish tip and animal carcasses were areas of
      concentrated activity for dogs and dingoes.

PMID- 30297604
TI  - Ethylenediamine Derived Carboxamides of Betulinic and Ursolic Acid as Potential
      Cytotoxic Agents.
AB  - Two easily accessible, natural occurring triterpenoids, betulinic and ursolic
      acid, were used as starting materials for the synthesis of novel cytotoxic
      agents. A set of 28 ethylenediamine-spacered carboxamides was prepared holding an
      additional substituent connected to the ethylenediamine group. The compounds were
      screened in SRB assays to evaluate their cytotoxic activity employing several
      human tumor cell lines. Betulinic acid-derived carboxamides 17-30 showed
      significantly higher cytotoxicity than their ursolic acid analogs 3-16. In
      particular, compounds 25 and 26 were highly cytotoxic, as indicated by EC50
      values lower than 1 MUM.

PMID- 30297605
TI  - Music-Based Therapeutic Interventions for People with Dementia: A Mini-Review.
AB  - The growing population of people with dementia worldwide calls attention to the
      burdens associated with age-related decline that affects physiology,
      psychological and cognitive status, and social/emotional wellbeing. The current
      standards in geriatric care recommend non-pharmacological approaches to these
      challenges, including safe approaches to managing pain and stress, enhancing
      symptom relief, and fostering independent lifestyles with the highest quality of
      life possible. The purpose of this article is to provide definitions of music
      based interventions, music therapy applications and clinician qualifications, as
      well as an umbrella mini-review of meta-analyses regarding music-based
      interventions for individuals with dementia. Our findings indicate that most
      descriptions of music therapy protocols in the research lack sufficient detail to
      enable researchers to compare and replicate studies, and clinicians to apply
      techniques. Definitions of music therapy and music-based interventions are
      inconsistent, and practitioners vary in their professional training and
      preparation for implementing music-based clinical strategies. We recommend that
      future researchers provide thorough descriptions of music therapy and music-based
      interventions in their protocols.

PMID- 30297606
TI  - Energy Efficient Hybrid Routing Protocol Based on the Artificial Fish Swarm
      Algorithm and Ant Colony Optimisation for WSNs.
AB  - Wireless Sensor Networks (WSNs) are a particular type of distributed self-managed
      network with limited energy supply and communication ability. The most
      significant challenge of a routing protocol is the energy consumption and the
      extension of the network lifetime. Many energy-efficient routing algorithms were
      inspired by the development of Ant Colony Optimisation (ACO). However, due to the
      inborn defects, ACO-based routing algorithms have a slow convergence behaviour
      and are prone to premature, stagnation phenomenon, which hinders further route
      discovery, especially in a large-scale network. This paper proposes a hybrid
      routing algorithm by combining the Artificial Fish Swarm Algorithm (AFSA) and ACO
      to address these issues. We utilise AFSA to perform the initial route discovery
      in order to find feasible routes quickly. In the route discovery algorithm, we
      present a hybrid algorithm by combining the crowd factor in AFSA and the pseudo
      random route select strategy in ACO. Furthermore, this paper presents an improved
      pheromone update method by considering energy levels and path length. Simulation
      results demonstrate that the proposed algorithm avoids the routing algorithm
      falling into local optimisation and stagnation, whilst speeding up the routing
      convergence, which is more prominent in a large-scale network. Furthermore,
      simulation evaluation reports that the proposed algorithm exhibits a significant
      improvement in terms of network lifetime.

PMID- 30297607
TI  - Bioelectrical Impedance Analysis Results for Estimating Body Composition Are
      Associated with Glucose Metabolism Following Laparoscopic Sleeve Gastrectomy in
      Obese Japanese Patients.
AB  - We investigated the association between body composition and changes in glucose
      metabolism following laparoscopic sleeve gastrectomy (LSG) in obese Japanese
      patients. Thirty-two Class III obese patients were assessed before LSG and 3, 6,
      and 12 months postoperatively. Variables including fat mass (FM), % body fat
      (%FM), total and skeletal muscle mass (MM), the ratio of lower extremity MM to
      body weight (BW) (L/W), and the ratio of upper extremity MM to BW (U/W) were
      measured while using bioelectrical impedance analysis (BIA). LSG significantly
      decreased BW, FM, and %FM in all time periods observed after surgery with
      concomitant improvements in metabolic markers. MM was decreased at three months
      but maintained from 3-12 months post-surgery. Importantly, %MM, U/W, and the L/W
      ratio increased after LSG. Furthermore, change in FM was positively correlated
      with change in BW 12 months after LSG, whereas changes in %MM were negatively
      correlated with fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). Finally,
      multivariable stepwise regression analyses showed that changes in % total MM was
      an independent determinant of FPG and change in % skeletal MM was a significant
      independent determinant of HbA1c in Class III obese Japanese patients after LSG.

PMID- 30297609
TI  - Trusted Cameras on Mobile Devices Based on SRAM Physically Unclonable Functions.
AB  - Nowadays, there is an increasing number of cameras placed on mobile devices
      connected to the Internet. Since these cameras acquire and process sensitive and
      vulnerable data in applications such as surveillance or monitoring, security is
      essential to avoid cyberattacks. However, cameras on mobile devices have
      constraints in size, computation and power consumption, so that lightweight
      security techniques should be considered. Camera identification techniques
      guarantee the origin of the data. Among the camera identification techniques,
      Physically Unclonable Functions (PUFs) allow generating unique, distinctive and
      unpredictable identifiers from the hardware of a device. PUFs are also very
      suitable to obfuscate secret keys (by binding them to the hardware of the device)
      and generate random sequences (employed as nonces). In this work, we propose a
      trusted camera based on PUFs and standard cryptographic algorithms. In addition,
      a protocol is proposed to protect the communication with the trusted camera,
      which satisfies authentication, confidentiality, integrity and freshness in the
      data communication. This is particularly interesting to carry out camera control
      actions and firmware updates. PUFs from Static Random Access Memories (SRAMs) are
      selected because cameras typically include SRAMs in its hardware. Therefore,
      additional hardware is not required and security techniques can be implemented at
      low cost. Experimental results are shown to prove how the proposed solution can
      be implemented with the SRAM of commercial Bluetooth Low Energy (BLE) chips
      included in the communication module of the camera. A proof of concept shows that
      the proposed solution can be implemented in low-cost cameras.

PMID- 30297608
TI  - Cyclopropane-Containing Fatty Acids from the Marine Bacterium Labrenzia sp. 011
      with Antimicrobial and GPR84 Activity.
AB  - Bacteria of the family Rhodobacteraceae are widespread in marine environments and
      known to colonize surfaces, such as those of e.g., oysters and shells. The marine
      bacterium Labrenzia sp. 011 is here investigated and it was found to produce two
      cyclopropane-containing medium-chain fatty acids (1, 2), which inhibit the growth
      of a range of bacteria and fungi, most effectively that of a causative agent of
      Roseovarius oyster disease (ROD), Pseudoroseovarius crassostreae DSM 16950.
      Additionally, compound 2 acts as a potent partial, beta-arrestin-biased agonist
      at the medium-chain fatty acid-activated orphan G-protein coupled receptor GPR84,
      which is highly expressed on immune cells. The genome of Labrenzia sp. 011 was
      sequenced and bioinformatically compared with those of other Labrenzia spp. This
      analysis revealed several cyclopropane fatty acid synthases (CFAS) conserved in
      all Labrenzia strains analyzed and a putative gene cluster encoding for two
      distinct CFASs is proposed as the biosynthetic origin of 1 and 2.

PMID- 30297610
TI  - Identification of Anti-Melanogenesis Constituents from Morus alba L. Leaves.
AB  - The individual parts of Morus alba L. including root bark, branches, leaves, and
      fruits are used as a cosmetic ingredient in many Asian countries. This study
      identified several anti-melanogenesis constituents in a 70% ethanol extract of M.
      alba leaves. The ethyl acetate fraction of the initial ethanol extract decreased
      the activity of tyrosinase, a key enzyme in the synthetic pathway of melanin.
      Twelve compounds were isolated from this fraction and their structures were
      identified based on spectroscopic spectra. Then, the authors investigated the
      anti-melanogenesis effects of the isolated compounds in B16-F10 mouse melanoma
      cells. Compounds 3 and 8 significantly inhibited not only melanin production but
      also intracellular tyrosinase activity in alpha-melanocyte-stimulating-hormone
      (alpha-MSH)-induced B16-F10 cells in a dose-dependent manner. These same
      compounds also inhibited melanogenesis-related protein expression such as
      microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase
      related protein-1 (TRP-1). Compound 3 modulated the cAMP-responsive element
      binding protein (CREB) and p38 signaling pathways in alpha-MSH-activated B16-F10
      melanoma cells, which resulted in the anti-melanogenesis effects. These results
      suggest that compound 3, isolated from M. alba leaves, could be used to inhibit
      melanin production via the regulation of melanogenesis-related protein
      expression.

PMID- 30297611
TI  - The Issue of Burnout and Work Satisfaction in Younger GPs-A Cluster Analysis
      Utilizing the HaMEdSi Study.
AB  - The shortage of general practitioners (GPs) in Germany has become a relevant
      problem. Therefore, it is important to find the determinants that make primary
      care more attractive, and which support GPs remaining in practice. Our aim in
      this exploratory study was to search for relevant GP subgroups and their
      characteristics in order to find starting points for improvements or
      interventions. We attempted a comprehensive survey of all GPs in the German
      region of Siegen-Wittgenstein with about 280,000 inhabitants. There were 158 GPs
      in the total population; 85 of these (53.8%) took part in the study. There were
      64 male GPs (75.3%) in our sample. The mean age of the participants was 53.5
      years (SD 8.93). The questionnaire was composed of demographic questions,
      questions regarding future perspectives, the Motivation for Medical Education
      Questionnaire (MoME-Q), the Maslach Burnout Inventory (MBI), and the Work
      Satisfaction Questionnaire. K-means cluster analyses were used for subgrouping. A
      2-cluster solution had good statistical quality criteria. Cluster 1 was
      characterised by elderly GPs who more frequently had a resident physician in
      their practices. These GPs had low burnout scores and high work satisfaction
      scores. Cluster 2 consisted of younger GPs who less frequently had a resident in
      their practices. They had average burnout scores according to published norms and
      lower work satisfaction scores. There seems to be an age cohort effect regarding
      burnout and work satisfaction. Having a resident physician seems to be
      protective. Interventions should be designed for younger GPs, especially members
      of generation Y, to reduce burnout and improve work satisfaction.

PMID- 30297614
TI  - Positioning Performance of BDS Observation of the Crustal Movement Observation
      Network of China and Its Potential Application on Crustal Deformation.
AB  - The Crustal Movement Observation Network of China (CMONOC) has begun receiving
      BeiDou Navigation Satellite System (BDS) observations since 2015, and accumulated
      more than 2.5 years of data. BDS observations has been widely applied in many
      fields, and long-term continuous data provide a new strategy for the study of
      crustal deformation in China. This paper focuses on the evaluation of BDS
      positioning performance and its potential application on crustal deformation in
      CMONOC. According to the comparative analysis on multipath delay (MPD) and signal
      to noise ratio (SNR) between BDS and GPS data, the data quality of BDS is at the
      same level with GPS measurements in COMONC. The spatial distribution of BDS
      positioning accuracy evaluated as the root mean square (RMS) of daily residual
      position time series on horizontal component is latitude-dependent, declining
      with the increasing of station latitude, while the vertical one is randomly
      distributed in China. The mean RMS of BDS position residual time series is 7 mm
      and 22 mm on horizontal and vertical components, respectively, and annual
      periodicity in position time series can be identified by BDS data. In view of the
      accuracy of BDS positioning, there are no systematic differences between GPS and
      BDS results. Based on time series analysis with data volume being 2.5 years, the
      noise characteristics of BDS daily position time series is time-correlated and
      corresponding noise is white plus flicker noise model, and the derived mean RMS
      of the BDS velocities is 1.2, 1.5, and 4.1 mm/year on north, east, and up
      components, respectively. The imperfect performance of BDS positioning relative
      to GPS is likely attributed to the relatively low accuracy of BDS ephemeris, and
      the sparse amount of MEO satellites distribution in the BDS constellation. It is
      expectable to study crustal deformation in CMONOC by BDS with the gradual
      maturity of its constellation and the accumulation of observations.

PMID- 30297613
TI  - Nb2O5 and Ti-Doped Nb2O5 Charge Trapping Nano-Layers Applied in Flash Memory.
AB  - High-k material charge trapping nano-layers in flash memory applications have
      faster program/erase speeds and better data retention because of larger
      conduction band offsets and higher dielectric constants. In addition, Ti-doped
      high-k materials can improve memory device performance, such as leakage current
      reduction, k-value enhancement, and breakdown voltage increase. In this study,
      the structural and electrical properties of different annealing temperatures on
      the Nb2O5 and Ti-doped Nb2O5(TiNb2O7) materials used as charge-trapping nano
      layers in metal-oxide-high k-oxide-semiconductor (MOHOS)-type memory were
      investigated using X-ray diffraction (XRD) and atomic force microscopy (AFM).
      Analysis of the C-V hysteresis curve shows that the flat-band shift (?VFB) window
      of the TiNb2O7 charge-trapping nano-layer in a memory device can reach as high as
      6.06 V. The larger memory window of the TiNb2O7 nano-layer is because of a better
      electrical and structural performance, compared to the Nb2O5 nano-layer.

PMID- 30297612
TI  - A Comprehensive Review of Arsenic Exposure and Risk from Rice and a Risk
      Assessment among a Cohort of Adolescents in Kunming, China.
AB  - Inorganic arsenic (iAs) is carcinogenic and highly concentrated in rice. Dietary
      exposure to iAs is concerning among adolescents due to their developmental stage
      and iAs's long-latency effects. This paper aimed to assess iAs exposure from rice
      and related lifetime cancer risks (LCR) among adolescents in Kunming, China. A
      comprehensive literature review of iAs levels in rice and LCR in humans was also
      conducted. Average daily consumption of rice (ADC) was estimated from 267
      adolescents (15-18 years). Rice samples obtained from 6 markets were analyzed for
      iAs concentration (AC). Estimated daily intake (EDI) of iAs was calculated using
      ADC, AC, and average body weight (BW). Lifetime Cancer Risk (LCR) was calculated
      using EDI and U.S. EPA derived iAs oral slope factor. The AC was 0.058 mg/kg and
      the average BW and ADC were 67.5 kg and 410 g/day for males and 55.5 kg and 337
      g/day for females. The EDI and LCR were 3.52 * 10-4 mg/kg-BW/day and 5.28 * 10-4
      for both males and females, with LCR 5 times above the U.S. LCR upper limit of
      1.0 * 10-4. While the AC was below the Chinese maximum contaminant level of 0.2
      mg/kg, study results indicated that Kunming adolescents may be at increased risk
      for iAs-related cancers.

PMID- 30297616
TI  - Interaction of Clostridium perfringens Iota Toxin and Lipolysis-Stimulated
      Lipoprotein Receptor (LSR).
AB  - Iota toxin produced by Clostridium perfringens is a binary, actin ADP
      ribosylating toxin that is organized into the enzymatically active component Ia
      and the binding component Ib. Lipolysis-stimulated lipoprotein receptor (LSR) has
      been identified as a cellular receptor of Ib. Here, we investigated the
      functional interaction between Ib and LSR, where siRNA for LSR blocked the toxin
      mediated cytotoxicity and the binding of Ib. The addition of Ib to LSR-green
      fluorescence protein (GFP)-transfected cells at 4  degrees C resulted in
      colocalization with LSR and Ib on the cell surface. Upon transfer of the cells
      from 4  degrees C to 37  degrees C, LSR and Ib were internalized and observed in
      cytoplasmic vesicles. When the cells were incubated with Ib at 37  degrees C and
      fractionated using the Triton-insoluble membrane, Ib oligomer was localized in
      insoluble factions that fulfilled the criteria of lipid rafts, and LSR was
      clustered in lipid rafts. To examine the interaction between N-terminal
      extracellular region of LSR and Ib, we constructed a series of LSR N-terminal
      deletions. Ten amino acids residues can be deleted from this end without any
      reduction of Ib binding. However, deletion of 15 N-terminal residues drastically
      reduces its ability to bind Ib. These results demonstrate that Ib binds to the
      LSR N-terminal 10 to 15 residues and endocytoses into trafficking endosomes
      together with LSR.

PMID- 30297615
TI  - Gut Microbiota's Relationship with Liver Disease and Role in Hepatoprotection by
      Dietary Natural Products and Probiotics.
AB  - A variety of dietary natural products have shown hepatoprotective effects.
      Increasing evidence has also demonstrated that gut microorganisms play an
      important role in the hepatoprotection contributed by natural products. Gut
      dysbiosis could increase permeability of the gut barrier, resulting in
      translocated bacteria and leaked gut-derived products, which can reach the liver
      through the portal vein and might lead to increased oxidative stress and
      inflammation, thereby threatening liver health. Targeting gut microbiota
      modulation represents a promising strategy for hepatoprotection. Many natural
      products could protect the liver from various injuries or mitigate hepatic
      disorders by reverting gut dysbiosis, improving intestinal permeability, altering
      the primary bile acid, and inhibiting hepatic fatty acid accumulation. The
      mechanisms underlying their beneficial effects also include reducing oxidative
      stress, suppressing inflammation, attenuating fibrosis, and decreasing apoptosis.
      This review discusses the hepatoprotective effects of dietary natural products
      via modulating the gut microbiota, mainly focusing on the mechanisms of action.

PMID- 30297618
TI  - Antiradical and Xanthine Oxidase Inhibitory Activity Evaluations of Averrhoa
      bilimbi L. Leaves and Tentative Identification of Bioactive Constituents through
      LC-QTOF-MS/MS and Molecular Docking Approach.
AB  - The objective of the present study was to investigate the antiradical and
      xanthine oxidase inhibitory effects of Averrhoa bilimbi leaves. Hence, crude
      methanolic leaves extract and its resultant fractions, namely hexane, chloroform,
      and n-butanol were evaluated for 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical
      scavenging effect and xanthine oxidase inhibitory activity. The active
      constituents were tentatively identified through LC-QTOF-MS/MS and molecular
      docking approaches. The n-butanol fraction of A. bilimbi crude methanolic leaves
      extract displayed significant DPPH radical scavenging effect with IC50 (4.14 +/-
      0.21 MUg/mL) (p < 0.05), as well as xanthine oxidase inhibitory activity with
      IC50 (64.84 +/- 3.93 MUg/mL) (p < 0.05). Afzelechin 3-O-alpha-l-rhamnopyranoside
      and cucumerin A were tentatively identified as possible metabolites that
      contribute to the antioxidant activity of the n-butanol fraction.

PMID- 30297617
TI  - Pain in Mucopolysaccharidoses: Analysis of the Problem and Possible Treatments.
AB  - Mucopolysaccharidosis (MPS) are a group of lysosomal storage disorders that are
      caused by the deficiency of enzymes involving in the catabolism of
      glycosaminoglycan (GAGs). GAGs incompletely degraded accumulate in many sites,
      damaging tissues and cells, leading to a variety of clinical manifestations. Many
      of these manifestations are painful, but few data are available in the literature
      concerning the prevalence, etiology, and pathogenesis of pain in children with
      MPS. This review, through the analysis of the data available the in literature,
      underscores the relevant prevalence of pain in MPSs' children, provides the
      instruments to discern the etiopathogenesis of the disease and of pain,
      illustrates the available molecules for the management of pain and the possible
      advantages of non-pharmacological pain therapy in MPSs' patients.

PMID- 30297619
TI  - Fermentation: A Boon for Production of Bioactive Compounds by Processing of Food
      Industries Wastes (By-Products).
AB  - A large number of by-products or wastes are produced worldwide through various
      food industries. These wastes cause a serious disposable problem with the
      environment. So, now a day's different approaches are used for alternative use of
      these wastes because these by-products are an excellent source of various
      bioactive components such as polyphenols, flavonoids, caffeine, carotenoids,
      creatine, and polysaccharides etc. which are beneficial for human health.
      Furthermore, the composition of these wastes depends on the source or type of
      waste. Approximately half of the waste is lignocellulosic in nature produced from
      food processing industries. The dissimilar types of waste produced by food
      industries can be fortified by various processes. Fermentation is one of the
      oldest approaches and there are three types of fermentation processes that are
      carried out such as solid state, submerged and liquid fermentation used for
      product transformation into value added products through microorganisms.
      Selections of the fermentation process are product specific. Moreover, various
      studies were performed to obtain or fortified different bioactive compounds that
      are present in food industries by-products or wastes. Therefore, the current
      review article discussed various sources, composition and nutritive value
      (especially bioactive compounds) of these wastes and their management or
      augmentation of value-added products through fermentation.

PMID- 30297622
TI  - Interest Forwarding in Named Data Networking Using Reinforcement Learning.
AB  - In-network caching is one of the key features of information-centric networks
      (ICN), where forwarding entities in a network are equipped with memory with which
      they can temporarily store contents and satisfy en route requests. Exploiting in
      network caching, therefore, presents the challenge of efficiently coordinating
      the forwarding of requests with the volatile cache states at the routers. In this
      paper, we address information-centric networks and consider in-network caching
      specifically for Named Data Networking (NDN) architectures. Our proposal departs
      from the forwarding algorithms which primarily use links that have been selected
      by the routing protocol for probing and forwarding. We propose a novel adaptive
      forwarding strategy using reinforcement learning with the random neural network
      (NDNFS-RLRNN), which leverages the routing information and actively seeks new
      delivery paths in a controlled way. Our simulations show that NDNFS-RLRNN
      achieves better delivery performance than a strategy that uses fixed paths from
      the routing layer and a more efficient performance than a strategy that retrieves
      contents from the nearest caches by flooding requests.

PMID- 30297620
TI  - Spatiotemporal Changes in PM2.5 and Their Relationships with Land-Use and People
      in Hangzhou.
AB  - Increases in the extent and level of air pollution in Chinese cities have become
      a major concern of the public and burden on the government. While ample
      literature has focused on the status, changes and causes of air pollution
      (particularly on PM2.5 and PM10), significantly less is known on their effects on
      people. In this study we used Hangzhou, China, as our testbed to assess the
      direct impact of PM2.5 on youth populations that are more vulnerable to
      pollution. We used the ground monitoring data of air quality and Aerosol optical
      thickness (AOT) product from the Moderate Resolution Imaging Spectroradiometer
      (MODIS) for the spatiotemporal changes of PM2.5 by season in 2015. We further
      explored these distributions with land cover, population density and schools
      (kindergarten, primary school and middle school) to explore the potential impacts
      in seeking potential mitigation solutions. We found that the seasonal variation
      of PM2.5 concentration was winter > spring > autumn > summer. In Hangzhou, the
      percentage of land area exposed to PM2.5 > 50 ug m-3 accounted for 59.86% in
      winter, 56.62% in spring, 40.44% in autumn and 0% in summer, whereas these
      figures for PM2.5 of <35 ug m-3 were 70.01%, 5.28%, 5.17%, 4.16% in summer,
      winter, autumn and spring, respectively. As for land cover, forest experienced
      PM2.5 of 35-50 ug m-3 (i.e., lower than those of other cover types), likely due
      to the potential filtering and absorption function of the forests. More
      importantly, a quantitative index based on population-weighted exposure level
      (pwel) indicated that only 9.06% of the population lived in areas that met the
      national air quality standards. Only 1.66% (14,055) of infants and juveniles
      lived in areas with PM2.5 of <35 ug m-3. Considering the legacy effects of PM2.5
      over the long-term, we highly recommend improving the monitoring systems for both
      air quality and people (i.e., their health conditions), with special attention
      paid to infants and juveniles.

PMID- 30297623
TI  - Separation and Bioactive Assay of 25R/S-Spirostanol Saponin Diastereomers from
      Yucca schidigera Roezl (Mojave) Stems.
AB  - In order to find a simple, generic, efficient separation method for 25R/S
      spirostanol saponin diastereomers, the liquid chromatographic retention behaviors
      of C12 carbonylation and C12 unsubstituted 25R/S-spirostanol saponin
      diastereomers on different stationary phases (C8, C18, C30 columns) and different
      mobile phases (MeOH-1% CH3COOH and CH3CN-1% CH3COOH) were investigated. A C30
      column was firstly found to offer the highest efficiency for the separation of
      this kind of diastereomers than C8 and C18 columns. Meanwhile, the analysis
      results indicated that both CH3CN-1% CH3COOH and MeOH-1% CH3COOH eluate systems
      were selective for C12 unsubstituted 25R/S-spirostanol saponin diastereomers,
      while MeOH-1% CH3COOH possessed better selectivity for C12 carbonylation ones.
      Using the abovementioned analysis method, six pairs of 25R/S-spirostanol saponin
      diastereomers 1a-6a and 1b-6b from Yucca schidigera Roezl (Mojave) were isolated
      successfully by using HPLC on C30 column for the first time. Among them, three
      pairs were new ones, named as (25R)-Yucca spirostanoside E1 (1a), (25S)-Yucca
      spirostanoside E1 (1b), (25R)-Yucca spirostanoside E2 (2a), (25S)-Yucca
      spirostanoside E2 (2b), (25R)-Yucca spirostanoside E3 (3a), (25S)-Yucca
      spirostanoside E3 (3b), respectively. Moreover, 3a, 5a, 6a, 3b-6b showed strong
      inhibitory activities on the growth of SW620 cell lines with the IC50 values of
      12.02-69.17 MUM.

PMID- 30297624
TI  - Phosphorylation of the AMPAR-TARP Complex in Synaptic Plasticity.
AB  - Synaptic plasticity has been considered a key mechanism underlying many brain
      functions including learning, memory, and drug addiction. An increase or decrease
      in synaptic activity of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid receptor (AMPAR) complex mediates the phenomena as shown in the cellular
      models of synaptic plasticity, long-term potentiation (LTP), and depression
      (LTD). In particular, protein phosphorylation shares the spotlight in expressing
      the synaptic plasticity. This review summarizes the studies on phosphorylation of
      the AMPAR pore-forming subunits and auxiliary proteins including transmembrane
      AMPA receptor regulatory proteins (TARPs) and discusses its role in synaptic
      plasticity.

PMID- 30297621
TI  - Peroxidase Activity of Human Hemoproteins: Keeping the Fire under Control.
AB  - The heme in the active center of peroxidases reacts with hydrogen peroxide to
      form highly reactive intermediates, which then oxidize simple substances called
      peroxidase substrates. Human peroxidases can be divided into two groups: (1) True
      peroxidases are enzymes whose main function is to generate free radicals in the
      peroxidase cycle and (pseudo)hypohalous acids in the halogenation cycle. The
      major true peroxidases are myeloperoxidase, eosinophil peroxidase and
      lactoperoxidase. (2) Pseudo-peroxidases perform various important functions in
      the body, but under the influence of external conditions they can display
      peroxidase-like activity. As oxidative intermediates, these peroxidases produce
      not only active heme compounds, but also protein-based tyrosyl radicals.
      Hemoglobin, myoglobin, cytochrome c/cardiolipin complexes and cytoglobin are
      considered as pseudo-peroxidases. Reroxidases play an important role in innate
      immunity and in a number of physiologically important processes like apoptosis
      and cell signaling. Unfavorable excessive peroxidase activity is implicated in
      oxidative damage of cells and tissues, thereby initiating the variety of human
      diseases. Hence, regulation of peroxidase activity is of considerable importance.
      Since peroxidases differ in structure, properties and location, the mechanisms
      controlling peroxidase activity and the biological effects of peroxidase products
      are specific for each hemoprotein. This review summarizes the knowledge about the
      properties, activities, regulations and biological effects of true and pseudo
      peroxidases in order to better understand the mechanisms underlying beneficial
      and adverse effects of this class of enzymes.

PMID- 30297625
TI  - Silicon-Mediated Enhancement of Heavy Metal Tolerance in Rice at Different Growth
      Stages.
AB  - Silicon (Si) plays important roles in alleviating heavy metal stress in rice
      plants. Here we investigated the physiological response of rice at different
      growth stages under the silicon-induced mitigation of cadmium (Cd) and zinc (Zn)
      toxicity. Si treatment increased the dry weight of shoots and roots and reduced
      the Cd and Zn concentrations in roots, stems, leaves and grains. Under the stress
      of exposure to Cd and Zn, photosynthetic parameters including the chlorophyll
      content and chlorophyll fluorescence decreased, while the membrane permeability
      and malondialdehyde (MDA) increased. Catalase (CAT) and peroxidase (POD)
      activities increased under heavy metals stress, but superoxide dismutase (SOD)
      activities decreased. The magnitude of these Cd- and Zn-induced changes was
      mitigated by Si-addition at different growth stages. The available Cd
      concentration increased in the soil but significantly decreased in the shoots,
      which suggested that Si treatment prevents Cd accumulation through internal
      mechanisms by limiting Cd2+ uptake by the roots. Overall, the phenomena of Si
      mediated alleviation of Cd and excess Zn toxicity in two rice cultivars could be
      due to the limitation of metal uptake and transport, resulting in an improvement
      in cell membrane integrity, photosynthetic performance and anti-oxidative enzyme
      activities after Si treatment.

PMID- 30297627
TI  - Mapping and QTL Analysis of Early-Maturity Traits in Tetraploid Potato (Solanum
      tuberosum L.).
AB  - Early maturity is one of the most important agronomical traits in potato
      breeding. To identify the DNA segment that codes for early maturity, a tetraploid
      potato segregation population of "Zhongshu 19" * "Zhongshu 3" was genetically
      analyzed, using a combination of high throughput simplified genome sequencing (2b
      RAD) and bulked segregant analysis (BSA). The DNA segment related to the early
      maturity trait was identified at the 3.7~4.2 Mb locus on the short arm of
      chromosome 5. Eight molecular markers were developed, of which five were closely
      linked to the early-maturity trait loci. Additionally, 42 simple sequence repeats
      (SSR) markers were constructed based on the reference sequence of Solanum
      tuberosum group Phureja DM1-3 516 R44 (DM). Using the TetraploidMap software, the
      linkage map of chromosome 5 was constructed with 50 markers. The total map length
      was 172 centiMorgan (cM), with an average genetic distance of 3.44 cM.
      Correlating molecular and phenotypic data of the segregating population, the
      mapped Quantitative Trait Loci (QTL) on the short arm of chromosome 5 contributed
      to 33.55% of the early-maturity phenotype. The early-maturity QTL was located at
      84 cM, flanked by the SSR5-85-1 and SCAR5-8 markers. The QTL was fine-mapped to
      471 kb. Using DNA sequence annotation, 34 genes were identified in this region,
      12 of them with unknown function. Among the other 22 annotated genes, E3
      ubiquitin ligase gene PUB14 could be related to maturity and regulation of tuber
      formation. The constructed QTL map is a useful basic tool for the cloning of
      early-maturity related genes in tetraploid potatoes.

PMID- 30297629
TI  - Calf Circumference as a Screening Tool for Cognitive Frailty in Community
      Dwelling Older Adults: The Korean Frailty and Aging Cohort Study (KFACS).
AB  - The aim of this study was to examine calf circumference in relation to cognitive
      frailty in community-dwelling older adults. Cross-sectional analysis was
      performed on the first-year baseline data of 1559 adults aged 70-84 years
      enrolled in the Korean Frailty and Aging Cohort Study. The final analysis
      included 1221 adults who were non-dependent in terms of instrumental activities
      of daily living, who underwent frailty and cognitive function assessments.
      Physical frailty was defined using the Fried Frailty Index. Cognitive impairment
      was defined as a score 1.5 standard deviations below the age-, sex- and education
      matched norms on any of four cognitive-function tests. The prevalence of
      cognitive frailty was 2.8% for men and 3.8% for women. After adjusting for
      potential confounders, in comparison to the "physically robust without cognitive
      impairment" group, the estimates of increased odds ratios (ORs) for low calf
      circumference (<32 cm) were much greater in the prefrail with cognitive
      impairment (OR 4.62, 95% confidence interval (CI): 2.02-10.61) and frail with
      cognitive impairment (OR 10.94, 95% CI: 2.87-41.68) groups in men but not in
      women. Low calf circumference was strongly related to cognitive frailty in men
      only, suggesting calf circumference can be used as an indicator of these
      outcomes.

PMID- 30297630
TI  - Optimization of Culture Condition for Ganoderic Acid Production in Ganoderma
      lucidum Liquid Static Culture and Design of a Suitable Bioreactor.
AB  - Ganoderma lucidum, a famous medicinal mushroom used worldwide, is a rich source
      of triterpenoids which, together with polysaccharides, are believed to be the
      main effective constituents of G. lucidum. With the increase of market demand,
      the wild resource is facing serious limitations, and the quality of cultivated
      fruiting bodies can be seriously affected by the availability of wood resources
      and by cultivation management practices. In the present study, we aimed to
      develop an alternative way to produce useful triterpenoids from G. lucidum. We
      cultured the strain using a two-stage liquid culture strategy and investigated
      the effects of nitrogen limitation, carbon supply, static culture volume and air
      supply in the static culture stage on the accumulation of five triterpenoids (GA
      P, GA-Q, GA-T, GA-S, GA-R). Our results showed that, under optimized condition,
      the total yield of the five triterpenoids reached 963 mg/L (as determined by
      HPLC). Among the five triterpenoids, GA-T accounted for about 75% of the total
      yield. Besides, a bioreactor suitable for fungal liquid static culture with a 10
      L extensible plastic bag shaped culture unit was designed and in which the
      maximum total yield of the five GAs reached 856.8 mg/L, and the GAs content
      reached 5.99%. Our results demonstrate the potential of industrial application of
      G. lucidum culture for the production of triterpenoids, especially GA-T. Air
      supply significantly improved the accumulation of triterpenoids, and this will
      provide important clues to understand why more triterpenoids are produced in the
      mycelia mat under static liquid culture conditions.

PMID- 30297626
TI  - Roles of Gut-Derived Secretory Factors in the Pathogenesis of Non-Alcoholic Fatty
      Liver Disease and Their Possible Clinical Applications.
AB  - The rising prevalence of non-alcoholic fatty liver disease (NAFLD) parallels the
      global increase in the number of people diagnosed with obesity and metabolic
      syndrome. The gut-liver axis (GLA) plays an important role in the pathogenesis of
      NAFLD/non-alcoholic steatohepatitis (NASH). In this review, we discuss the
      clinical significance and underlying mechanisms of action of gut-derived
      secretory factors in NAFLD/NASH, focusing on recent human studies. Several
      studies have identified potential causal associations between gut-derived
      secretory factors and NAFLD/NASH, as well as the underlying mechanisms. The
      effects of gut-derived hormone-associated drugs, such as glucagon-like peptide-1
      analog and recombinant variant of fibroblast growth factor 19, and other new
      treatment strategies for NAFLD/NASH have also been reported. A growing body of
      evidence highlights the role of GLA in the pathogenesis of NAFLD/NASH. Larger and
      longitudinal studies as well as translational research are expected to provide
      additional insights into the role of gut-derived secretory factors in the
      pathogenesis of NAFLD/NASH, possibly providing novel markers and therapeutic
      targets in patients with NAFLD/NASH.

PMID- 30297628
TI  - Prescribing Hemodialysis or Hemodiafiltration: When One Size Does Not Fit All the
      Proposal of a Personalized Approach Based on Comorbidity and Nutritional Status.
AB  - There is no simple way to prescribe hemodialysis. Changes in the dialysis
      population, improvements in dialysis techniques, and different attitudes towards
      the initiation of dialysis have influenced treatment goals and, consequently,
      dialysis prescription. However, in clinical practice prescription of dialysis
      still often follows a "one size fits all" rule, and there is no agreed
      distinction between treatment goals for the younger, lower-risk population, and
      for older, high comorbidity patients. In the younger dialysis population,
      efficiency is our main goal, as assessed by the demonstrated close relationship
      between depuration (tested by kinetic adequacy) and survival. In the ageing
      dialysis population, tolerance is probably a better objective: "good dialysis"
      should allow the patient to attain a stable metabolic balance with minimal
      dialysis-related morbidity. We would like therefore to open the discussion on a
      personalized approach to dialysis prescription, focused on efficiency in younger
      patients and on tolerance in older ones, based on life expectancy, comorbidity,
      residual kidney function, and nutritional status, with particular attention
      placed on elderly, high-comorbidity populations, such as the ones presently
      treated in most European centers. Prescription of dialysis includes reaching
      decisions on the following elements: dialysis modality (hemodialysis (HD) or
      hemodiafiltration (HDF)); type of membrane (permeability, surface); and the
      frequency and duration of sessions. Blood and dialysate flow, anticoagulation,
      and reinfusion (in HDF) are also briefly discussed. The approach described in
      this concept paper was developed considering the following items: nutritional
      markers and integrated scores (albumin, pre-albumin, cholesterol; body size, Body
      Mass Index (BMI), Malnutrition Inflammation Score (MIS), and Subjective Global
      Assessment (SGA)); life expectancy (age, comorbidity (Charlson Index), and
      dialysis vintage); kinetic goals (Kt/V, normalized protein catabolic rate (n
      PCR), calcium phosphate, parathyroid hormone (PTH), beta-2 microglobulin);
      technical aspects including vascular access (fistula versus catheter, degree of
      functionality); residual kidney function and weight gain; and dialysis tolerance
      (intradialytic hypotension, post-dialysis fatigue, and subjective evaluation of
      the effect of dialysis on quality of life). In the era of personalized medicine,
      we hope the approach described in this concept paper, which requires validation
      but has the merit of providing innovation, may be a first step towards raising
      attention on this issue and will be of help in guiding dialysis choices that
      exploit the extraordinary potential of the present dialysis "menu".

PMID- 30297631
TI  - Neuromodulation of Synaptic Transmission in the Main Olfactory Bulb.
AB  - A major step in our understanding of brain function is to determine how neural
      circuits are altered in their function by signaling molecules or neuromodulators.
      Neuromodulation is the neurochemical process that modifies the computations
      performed by a neuron or network based on changing the functional needs or
      behavioral state of the subject. These modulations have the effect of altering
      the responsivity to synaptic inputs. Early sensory processing areas, such as the
      main olfactory bulb, provide an accessible window for investigating how
      neuromodulation regulates the functional states of neural networks and influences
      how we process sensory information. Olfaction is an attractive model system in
      this regard because of its relative simplicity and because it links primary
      olfactory sensory neurons to higher olfactory and associational networks.
      Likewise, centrifugal fibers from higher order brain centers target neurons in
      the main olfactory bulb to regulate synaptic processing. The neuromodulatory
      systems that provide regulatory inputs and play important roles in olfactory
      sensory processing and behaviors include the endocannabinoid system, the
      dopaminergic system, the cholinergic system, the noradrenergic system and the
      serotonergic system. Here, we present a brief survey of neuromodulation of
      olfactory signals in the main olfactory bulb with an emphasis on the
      endocannabinoid system.

PMID- 30297632
TI  - Systematic Screening of Commonly Used Commercial Transfection Reagents towards
      Efficient Transfection of Single-Stranded Oligonucleotides.
AB  - Non-viral vector-mediated transfection is a core technique for in vitro screening
      of oligonucleotides. Despite the growing interests in the development of
      oliogonucleotide-based drug molecules in recent years, a comprehensive comparison
      of the transfection efficacy of commonly used commercial transfection reagents
      has not been reported. In this study, five commonly used transfection reagents,
      including Lipofectamine 3000, Lipofectamine 2000, Fugene, RNAiMAX and Lipofectin,
      were comprehensively analyzed in ten cell lines using a fluorescence imaging
      based transfection assay. Although the transfection efficacy and toxicity of
      transfection reagents varied depending on cell types, the toxicity of
      transfection reagents generally displayed a positive correlation with their
      transfection efficacy. According to our results, Lipofectamine 3000, Fugene and
      RNAiMAX showed high transfection efficacy, however, RNAiMAX may be a better
      option for majority of cells when lower toxicity is desired. The transfection
      efficacy of Lipofectamine 2000 was compromised by its high toxicity, which may
      adversely affect its application in most cells. We firmly believe that our
      findings may contribute to the future In vitro delivery and screening of single
      stranded therapeutic oligonucleotides such as antisense oligonucleotides,
      antimiRs, and DNAzymes.

PMID- 30297633
TI  - Effect of Differential Speed Rotation Technology on the Forming Uniformity in
      Flexible Rolling Process.
AB  - As the local forming non-uniform of the formed curved surface part with larger
      bending deformation is the one of common defects, the utilization ratio of metal
      plate greatly reduces due to this defect, and cost of production is also
      increasing. In this paper, the differential speed rotation technology of flexible
      rolling process was proposed firstly to solve this forming defect. The finite
      element model was established, the reason of the local forming non-uniform was
      discussed; the effect of differential speed rotation technology on the forming
      uniform was studied. The results show that: Flexible rolling is a process based
      on thickness reduction, in this forming process, the thickness reduces sharply
      near the back end of metal plate, the local forming non-uniform of formed curved
      surface part is caused during this process; the differential speed rotation
      technology is applied in flexible rolling, with increasing rotation speed
      difference between upper and lower roll set, the forming uniformity of the formed
      curved surface part is greatly improved. The results of numerical simulation are
      in agreement with the result of forming experiments.

PMID- 30297635
TI  - Pharmacokinetic Properties of Acetyl Tributyl Citrate, a Pharmaceutical
      Excipient.
AB  - Acetyl tributyl citrate (ATBC) is an (the Food and Drug Administration) FDA
      approved substance for use as a pharmaceutical excipient. It is used in
      pharmaceutical coating of solid oral dosage forms such as coated tablets or
      capsules. However, the information of ATBC on its pharmacokinetics is limited.
      The aim of this study is to investigate the pharmacokinetic properties of ATBC
      using liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. ATBC
      was rapidly absorbed and eliminated and the bioavailability was 27.4% in rats.
      The results of metabolic stability tests revealed that metabolic clearance may
      have accounted for a considerable portion of the total clearance of ATBC. These
      pharmacokinetic data would be useful in studies investigating the safety and
      toxicity of ATBC.

PMID- 30297634
TI  - Opposite Regulation of CHOP and GRP78 and Synergistic Apoptosis Induction by
      Selenium Yeast and Fish Oil via AMPK Activation in Lung Adenocarcinoma Cells.
AB  - Selenium has been intensively studied for the use of cancer prevention and
      treatment. However, the clinical effects are still plausible. To enhance its
      efficacy, a combinational study of selenium yeast (SY) and fish oil (FO) was
      performed in A549, CL1-0, H1299, HCC827 lung adenocarcinoma (LADC) cells to
      investigate the enhancement in apoptosis induction and underlying mechanism. By
      sulforhodamine B staining, Western blot and flow cytometric assays, we found a
      synergism between SY and FO in growth inhibition and apoptosis induction of LADC
      cells. In contrast, the fetal lung fibroblast cells (MRC-5) were unsusceptible to
      this combination effect. FO synergized SY-induced apoptosis of A549 cells,
      accompanied with synergistic activation of AMP-activated protein kinase (AMPK)
      and reduction of Cyclooxygenase (COX)-2 and beta-catenin. Particularly, combining
      with FO not only enhanced the SY-elevated proapoptotic endoplasmic reticulum (ER)
      stress marker CCAAT/enhancer-binding protein homologous protein (CHOP), but also
      reduced the cytoprotective glucose regulated protein of molecular weight 78 kDa
      (GRP78). Consequently, the CHOP downstream targets such as phospho-JNK and death
      receptor 5 were also elevated, along with the cleavage of caspase-8, -3, and the
      ER stress-related caspase-4. Accordingly, inhibition of AMPK by compound C
      diminished the synergistic apoptosis induction, and elevated CHOP/GRP78 ratio by
      SY combined with FO. The AMPK-dependent synergism suggests the combination of SY
      and FO for chemoprevention and integrative treatment of LADC.

PMID- 30297636
TI  - Reduction of Real-Time Imaging of M1 Macrophage Chemotaxis toward Damaged Muscle
      Cells is PI3K-Dependent.
AB  - Macrophages migrate and invade into damaged muscle rapidly and are important for
      muscle repair and subsequent regeneration. The exact cellular and biological
      events that cause macrophage migration toward injured muscle are not completely
      understood. In this study, the effect of macrophage differentiation on the
      chemotactic capability to invade local damaged muscle was investigated using an
      in vitro model of muscle injury. We used C2C12 cell myoblasts and J774 cell
      macrophages, and the "killed-C2C12" cells were combined with live C2C12 cells as
      a partially damaged muscle model. The cultured J774 cells, with or without
      lipopolysaccharide (LPS), were treated with Ly294002 (Ly), which is an inhibitor
      of phosphoinositide 3-kinase (PI3K). In order to evaluate the polarization effect
      of LPS stimulation on J774 cells, expression of cell surface Toll-like receptor 4
      (TLR4), CD11c and CCR2, and expression of F-actin intensity, were analyzed by
      flow cytometry. The real-time horizontal chemotaxis assay of J774 cells was
      tested using the TAXIScan device. The expressions of TLR4, CD11c, and F-actin
      intensity in LPS-treated cells were significantly higher than those in Ctrl
      cells. In LPS-treated cells, the chemotactic activity toward damaged muscle cells
      completely disappeared. Moreover, the reduced chemotaxis depended far more on
      directionality than velocity. However, Ly treatment reversed the reduced
      chemotactic activity of the LPS-treated cells. In addition, cell-adhesion and F
      actin intensity, but not CCR2 expression, in LPS-treated cells, was significantly
      reduced by Ly treatment. Taken together, our results suggest that the PI3K/Akt
      activation state drives migration behavior towards damaged muscle cells.

PMID- 30297637
TI  - Does Residential Green and Blue Space Promote Recovery in Psychotic Disorders? A
      Cross-Sectional Study in the Province of Utrecht, The Netherlands.
AB  - Mental health is reportedly influenced by the presence of green and blue space in
      residential areas, but scientific evidence of a relation to psychotic disorders
      is scant. We put two hypotheses to the test: first, compared to the general
      population, psychiatric patients live in neighborhoods with less green and blue
      space; second, the amount of green and blue space is negatively associated with
      the duration of hospital admission. The study population consisted of 623
      patients with psychotic disorders who had been admitted to the psychiatric ward
      of an academic hospital in Utrecht, The Netherlands from 2008 to 2016. Recovery
      was measured by length of stay. Structured patient data was linked to socio
      economic status and the amount of green and blue space in the residential area.
      Associations were assessed by means of regression models controlling for
      confounding factors. Compared to the general population, psychiatric patients had
      a significantly lower amount of green space in their neighborhood. This result
      was not confirmed for blue space. Furthermore, no significant associations were
      found between green and blue space and the duration of hospital stay. In
      conclusion, previous studies focusing on other mental disorders, like anxiety or
      depression, found positive mental health effects of green and blue space in the
      neighborhood. We were not able to confirm significant effects among our study
      population on duration of admission, however. Future research focusing on
      psychotic patients could investigate the influence of exposure to green and blue
      space on other influences and outcomes on mental health.

PMID- 30297638
TI  - Metabolic Stability and Metabolite Characterization of Capilliposide B and
      Capilliposide C by LC-QTRAP-MS/MS.
AB  - Capilliposide B (LC-B) and Capilliposide C (LC-C), two new triterpenoid saponins
      extracted from Lysimachia capillipes Hemsl, exhibit potential anticancer activity
      both in vitro and in vivo. However, their metabolic process remains unclear. In
      this study, the metabolic stability of LC-B, LC-C, and Capilliposide A (LC-A, a
      bioactive metabolite of LC-B and LC-C) was investigated in human, rat, and mouse
      liver microsomes, respectively. Thereafter, their metabolites were identified and
      characterized after oral administration in mice. As a result, species difference
      was found in the metabolic stability of LC-B and LC-C. All three compounds of
      interest were stable in human and rat liver microsomes, but LC-B and LC-C
      significantly degraded in mouse liver microsomes. The metabolic instability of LC
      B and LC-C was mainly caused by esterolysis. Moreover, 19 metabolites were
      identified and characterized in mouse biological matrices. LC-B and LC-C mainly
      underwent deglycosylation and esterolysis, accompanied by dehydration,
      dehydrogenation, and hydroxylation as minor metabolic reactions. Finally, the
      metabolic pathway of LC-B and LC-C in mice was proposed. Our results updated the
      preclinical metabolism and disposition process of LC-B and LC-C, which provided
      additional information for better understanding efficacy and safety.

PMID- 30297639
TI  - Automatic Rectification of the Hybrid Stereo Vision System.
AB  - By combining the advantages of 360-degree field of view cameras and the high
      resolution of conventional cameras, the hybrid stereo vision system could be
      widely used in surveillance. As the relative position of the two cameras is not
      constant over time, its automatic rectification is highly desirable when adopting
      a hybrid stereo vision system for practical use. In this work, we provide a
      method for rectifying the dynamic hybrid stereo vision system automatically. A
      perspective projection model is proposed to reduce the computation complexity of
      the hybrid stereoscopic 3D reconstruction. The rectification transformation is
      calculated by solving a nonlinear constrained optimization problem for a given
      set of corresponding point pairs. The experimental results demonstrate the
      accuracy and effectiveness of the proposed method.

PMID- 30297642
TI  - Low Praziquantel Treatment Coverage for Schistosoma mansoni in Mayuge District,
      Uganda, Due to the Absence of Treatment Opportunities, Rather Than Systematic Non
      Compliance.
AB  - The World Health Organization (WHO) recommends praziquantel mass drug
      administration (MDA) to control schistosomiasis in endemic regions. We aimed to
      quantify recent and lifetime praziquantel coverage, and reasons for non
      treatment, at an individual level to guide policy recommendations to help Uganda
      reach WHO goals. Cross-sectional household surveys (n = 681) encompassing 3208
      individuals (adults and children) were conducted in 2017 in Bugoto A and B,
      Mayuge District, Uganda. Participants were asked if they had received
      praziquantel during the recent MDA (October 2016) and whether they had ever
      received praziquantel in their lifetime. A multivariate logistic regression
      analysis with socio-economic and individual characteristics as covariates was
      used to determine factors associated with praziquantel uptake. In the MDA
      eligible population (>=5 years of age), the most recent MDA coverage was 48.8%.
      Across individuals' lifetimes, 31.8% of eligible and 49.5% of the entire
      population reported having never taken praziquantel. Factors that improved
      individuals' odds of taking praziquantel included school enrolment, residence in
      Bugoto B and increasing years of village-residency. Not being offered (49.2%) and
      being away during treatment (21.4%) were the most frequent reasons for not taking
      the 2016 praziquantel MDA. Contrary to expectations, chronically-untreated
      individuals were rarely systematic non-compliers, but more commonly not offered
      treatment.

PMID- 30297641
TI  - Poly-Gamma-Glutamic Acid (gamma-PGA)-Based Encapsulation of Adenovirus to Evade
      Neutralizing Antibodies.
AB  - In recent years, there has been an increasing interest in oncolytic adenoviral
      vectors as an alternative anticancer therapy. The induction of an immune response
      can be considered as a major limitation of this kind of application. Significant
      research efforts have been focused on the development of biodegradable polymer
      poly-gamma-glutamic acid (gamma-PGA)-based nanoparticles used as a vector for
      effective and safe anticancer therapy, owing to their controlled and sustained
      release properties, low toxicity, as well as biocompatibility with tissue and
      cells. This study aimed to introduce a specific destructive and antibody blind
      polymer-coated viral vector into cancer cells using gamma-PGA and chitosan (CH).
      Adenovirus was successfully encapsulated into the biopolymer particles with an
      encapsulation efficiency of 92% and particle size of 485 nm using the ionic
      gelation method. Therapeutic agents or nanoparticles (NPs) that carry
      therapeutics can be directed specifically to cancerous cells by decorating their
      surfaces using targeting ligands. Moreover, in vitro neutralizing antibody
      response against viral capsid proteins can be somewhat reduced by encapsulating
      adenovirus into gamma-PGA-CH NPs, as only 3.1% of the encapsulated adenovirus was
      detected by anti-adenovirus antibodies in the presented work compared to naked
      adenoviruses. The results obtained and the unique characteristics of the polymer
      established in this research could provide a reference for the coating and
      controlled release of viral vectors used in anticancer therapy.

PMID- 30297640
TI  - Transcriptome Sequencing Reveals the Differentially Expressed lncRNAs and mRNAs
      Involved in Cryoinjuries in Frozen-Thawed Giant Panda (Ailuropoda melanoleuca)
      Sperm.
AB  - Sperm cryopreservation and artificial insemination are important methods for
      giant panda breeding and preservation of extant genetic diversity. Lower
      conception rates limit the use of artificial insemination with frozen-thawed
      giant panda sperm, due to the lack of understanding of the cryodamaging or
      cryoinjuring mechanisms in cryopreservation. Long non-coding RNAs (lncRNAs) are
      involved in regulating spermatogenesis. However, their roles during
      cryopreservation remain largely unexplored. Therefore, this study aimed to
      identify differentially expressed lncRNAs and mRNAs associated with cryodamage or
      freeze tolerance in frozen-thawed sperm through high throughput sequencing. A
      total of 61.05 Gb clean reads and 22,774 lncRNA transcripts were obtained. From
      the sequencing results, 1477 significantly up-regulated and 1,396 significantly
      down-regulated lncRNA transcripts from fresh and frozen-thawed sperm of giant
      panda were identified. GO and KEGG showed that the significantly dysregulated
      lncRNAs and mRNAs were mainly involved in regulating responses to cold stress and
      apoptosis, such as the integral component of membrane, calcium transport, and
      various signaling pathways including PI3K-Akt, p53 and cAMP. Our work is the
      first systematic profiling of lncRNA and mRNA in fresh and frozen-thawed giant
      panda sperm, and provides valuableinsights into the potential mechanism of
      cryodamage in sperm.

PMID- 30297644
TI  - New Insights into Development of Transglutaminase 2 Inhibitors as Pharmaceutical
      Lead Compounds.
AB  - Transglutaminase 2 (EC 2.3.2.13; TG2 or TGase 2) plays important roles in the
      pathogenesis of many diseases, including cancers, neurodegeneration, and
      inflammatory disorders. Under normal conditions, however, mice lacking TGase 2
      exhibit no obvious abnormal phenotype. TGase 2 expression is induced by chemical,
      physical, and viral stresses through tissue-protective signaling pathways. After
      stress dissipates, expression is normalized by feedback mechanisms. Dysregulation
      of TGase 2 expression under pathologic conditions, however, can potentiate
      pathogenesis and aggravate disease severity. Consistent with this, TGase 2
      knockout mice exhibit reversal of disease phenotypes in neurodegenerative and
      chronic inflammatory disease models. Accordingly, TGase 2 is considered to be a
      potential therapeutic target. Based on structure-activity relationship assays
      performed over the past few decades, TGase 2 inhibitors have been developed that
      target the enzyme's active site, but clinically applicable inhibitors are not yet
      available. The recently described the small molecule GK921, which lacks a group
      that can react with the active site of TGase 2, and efficiently inhibits the
      enzyme's activity. Mechanistic studies revealed that GK921 binds at an allosteric
      binding site in the N-terminus of TGase 2 (amino acids (a.a.) 81-116), triggering
      a conformational change that inactivates the enzyme. Because the binding site of
      GK921 overlaps with the p53-binding site of TGase 2, the drug induces apoptosis
      in renal cell carcinoma by stabilizing p53. In this review, we discuss the
      possibility of developing TGase 2 inhibitors that target the allosteric binding
      site of TGase 2.

PMID- 30297643
TI  - Characterization of a Novel N-Acylhomoserine Lactonase RmmL from Ruegeria mobilis
      YJ3.
AB  - Gram-negative bacteria utilize N-acylhomoserine lactones (AHLs) as quorum sensing
      (QS) signaling molecules for intercellular communication. Cell-to-cell
      communication depends on cell population density, and AHL-dependent QS is related
      to the production of multiple genes including virulence factors. Quorum quenching
      (QQ), signal inactivation by enzymatic degradation, is a potential strategy for
      attenuating QS regulated bacterial infections. Both Gram-positive and -negative
      bacteria have QQ enzymes that can degrade AHLs. In our previous study, strain
      Ruegeria mobilis YJ3, isolated from healthy shrimp, showed strong AHLs
      degradative activity. In the current study, an AHL lactonase (designated RmmL)
      was cloned and characterized from Ruegeria mobilis YJ3. Amino acid sequence
      analysis showed that RmmL has a conserved "HXHXDH" motif and clusters together
      with lactonase AidC that belongs to the metallo-beta-lactamase superfamily.
      Recombinant RmmL could degrade either short- or long-chain AHLs in vitro. High
      performance liquid chromatography analysis indicated that RmmL works as an AHL
      lactonase catalyzing AHL ring-opening by hydrolyzing lactones. Furthermore, RmmL
      can reduce the production of pyocyanin by Pseudomonas aeruginosa PAO1, while for
      the violacein and the extracellular protease activities by Chromobacterium
      violaceum CV026 and Vibrio anguillarum VIB72, no significant reduction was
      observed. This study suggests that RmmL might be used as a therapeutic agent in
      aquaculture.

PMID- 30297645
TI  - Preparation of Self-supporting Bagasse Cellulose Nanofibrils Hydrogels Induced by
      Zinc Ions.
AB  - Cellulose hydrogels are often prepared from native cellulose through a direct
      cellulose dissolution approach that often involves tedious process and solvent
      recovery problems. A self-supporting cellulose hydrogel was prepared by gelation
      of the TEMPO-oxidized bagasse cellulose nanofibrils (CNF) triggered by strong
      crosslinking between carboxylate groups and Zn2+. TEMPO process was used to
      generate negatively charged carboxylate groups on CNF surface to provide a high
      binding capability to Zn2+. Three TEMPO-oxidized CNFs of different carboxylate
      contents were prepared and characterized. TEM and AFM microscopes suggested that
      the sizes of CNFs were fined down and carboxylated cellulose nanofibrils (TOCNFs)
      of 5-10 nm wide, 200-500 nm long, and carboxylate contents 0.73-1.29 mmol/g were
      obtained. The final structures and compressive strength of hydrogels were
      primarily influenced by interfibril Zn2+-carboxylate interactions, following the
      order of TOCNFs concentration > content of carboxylate groups > concentration of
      zinc ions. A CO2 sensitive self-supporting cellulose hydrogel was developed as a
      colorimetric indicator of food spoilage for intelligent food packaging
      applications.

PMID- 30297646
TI  - A Comprehensive Study on the Biological Activity of Elderberry Extract and
      Cyanidin 3-O-Glucoside and Their Interactions with Membranes and Human Serum
      Albumin.
AB  - In our research we used the extract from dietary supplement of elderberry (EE)
      and its dominant anthocyanin-cyanidin 3-O-glucoside (Cy 3-gluc). By interacting
      with a model membrane that reflects the main lipid composition of tumor
      membranes, the extract components, including Cy 3-gluc, caused an increase in
      packing order, mainly in the hydrophilic region of the membrane. It can thus be
      stated that EE caused a rigidifying effect, which is fundamental for
      understanding its anticancer and antioxidant activity. This study represents the
      first attempt to unravel the mechanism of interaction of elderberry extract with
      membranes. The results of the interaction with human serum albumin (HSA) proved
      that the studied substance quenches the fluorescence of HSA through a static
      mechanism in which the main interaction forces are Van der Waals and hydrogen
      bonding. The antioxidant activity of EE and Cy 3-gluc on liposomal membranes,
      antiradical properties and ability to inhibited the activity of the enzymes
      cyclooxygenase-1 and cyclooxygenase-2 were also demonstrated. Moreover, the
      anticancer activity of EE and Cy 3-gluc on human breast adenocarcinoma cell line
      were investigated. In addition, EE also exhibited the ability to form lipid
      aggregates in the form of liposomal capsules that can be applied as carriers of
      active biological substances, and the highest efficacy of EE encapsulation was
      obtained for multilayered liposome formulations.

PMID- 30297647
TI  - Enhanced Pulsatile Growth Hormone Secretion and Altered Metabolic Hormones by in
      Vivo Hexarelin Treatment in Streptozotocin-Induced Diabetic Rats.
AB  - Significant growth hormone (GH) reductions have been reported in diabetic animal
      models with disturbed metabolic balance coinciding with GH deficiency. Therefore,
      enhanced GH secretion may have beneficial effects in controlling diabetes. Thus,
      we aim to investigate the effect of hexarelin, a synthetic GH secretagogue (GHS),
      on GH secretion in streptozotocin (STZ, 65 mg/kg)-induced diabetic rats. Daily
      hexarelin (100 MUg/kg) treatment was performed for two weeks in four-week-long
      STZ-diabetic and vehicle control rats. Pulsatile GH secretion in STZ-rats was
      significantly reduced in total, pulsatile, basal, and mass of GH secretion per
      burst. In addition, impaired GH secretion was followed by an increase in fasting
      level free fatty acids (FFAs) and a decrease in insulin-like growth factor 1 (IGF
      1) compared to control rats. After hexarelin treatment, pulsatile GH secretion in
      STZ-rats was significantly increased in total, pulsatile, and basal, but not in
      the mass GH secretion per burst, compared to STZ-rats without hexarelin
      treatment. However, there was no significant elevation in GH secretion in the
      hexarelin-treated control group. In addition, hexarelin-treated STZ-rats showed a
      significant decrease in fasting level FFAs, whereas suppression of fasting level
      for IGF-1 was maintained. These results suggest that STZ-induced diabetic rats
      have impaired pulsatile GH secretion, causing increased FFAs and decreased IGF-1
      levels in circulation. Hexarelin injections for two weeks is able to normalize
      impaired pulsatile GH secretion with normal fasting levels of FFAs, but fails to
      recover IGF-1 levels.

PMID- 30297649
TI  - A Novel Fault Location Method for a Cross-Bonded HV Cable System Based on Sheath
      Current Monitoring.
AB  - In order to improve the practice in the operation and maintenance of high voltage
      (HV) cables, this paper proposes a fault location method based on the monitoring
      of cable sheath currents for use in cross-bonded HV cable systems. This method
      first analyzes the power-frequency component of the sheath current, which can be
      acquired at cable terminals and cable link boxes, using a Fast Fourier Transform
      (FFT). The cable segment where a fault occurs can be localized by the phase
      difference between the sheath currents at the two ends of the cable segment,
      because current would flow in the opposite direction towards the two ends of the
      cable segment with fault. Conversely, in other healthy cable segments of the same
      circuit, sheath currents would flow in the same direction. The exact fault
      position can then be located via electromagnetic time reversal (EMTR) analysis of
      the fault transients of the sheath current. The sheath currents have been
      simulated and analyzed by assuming a single-phase short-circuit fault to occur in
      every cable segment of a selected cross-bonded high voltage cable circuit. The
      sheath current monitoring system has been implemented in a 110 kV cable circuit
      in China. Results indicate that the proposed method is feasible and effective in
      location of HV cable short circuit faults.

PMID- 30297648
TI  - Characterization of Apoptosis, Autophagy and Oxidative Stress in Pancreatic
      Islets Cells and Intestinal Epithelial Cells Isolated from Equine Metabolic
      Syndrome (EMS) Horses.
AB  - Endocrine disorders are becoming an increasing problem in both human and
      veterinary medicine. In recent years, more and more horses worldwide have been
      suffering from equine metabolic syndrome (EMS). This metabolic disorder is
      characterized by pathological obesity, hyperinsulinaemia, hyperglycaemia and
      insulin resistance. Although metabolic disorders, including diabetes, have been
      extensively studied, there are still no data on the molecular effects of EMS in
      horses. Thus, the aim of this study was to evaluate apoptosis, oxidative stress,
      autophagy and microRNA (miR) expression in multipotent intestinal epithelial stem
      cells (IECs) and pancreatic islets (PIs) isolated post mortem form healthy and
      EMS diagnosed horses. Our group was the first to describe how EMS affects IEC and
      PI aging and senescence. First, we evaluated isolation and culture protocol for
      these cells and subsequently established their metabolic status in vitro. Both
      IECs and PIs isolated from EMS horses were characterized by increased apoptosis
      and senescence. Moreover, they accumulated elevated levels of reactive oxygen
      species (ROS). Here we have observed that autophagy/mitophagy may be a protective
      mechanism which allows those cells to maintain their physiological function,
      clear protein aggregates and remove damaged organelles. Furthermore, it may play
      a crucial role in reducing endoplasmic reticulum (ER) stress. This protective
      mechanism may help to overcome the harmful effects of ROS and provide building
      blocks for protein and ATP synthesis.

PMID- 30297650
TI  - Her2-Targeted Therapy Induces Autophagy in Esophageal Adenocarcinoma Cells.
AB  - Esophageal adenocarcinoma (EAC) is a highly lethal cancer type with an overall
      poor survival rate. Twenty to thirty percent of EAC overexpress the human
      epidermal growth factor receptor 2 (Her2), a transmembrane receptor tyrosine
      kinase promoting cell growth and proliferation. Patients with Her2 overexpressing
      breast and gastroesophageal cancer may benefit from Her2 inhibitors. Therapy
      resistance, however, is well documented. Since autophagy, a lysosome-dependent
      catabolic process, is implicated in cancer resistance mechanisms, we tested
      whether autophagy modulation influences Her2 inhibitor sensitivity in EAC. Her2
      positive OE19 EAC cells showed an induction in autophagic flux upon treatment
      with the small molecule Her2 inhibitor Lapatinib. Newly generated Lapatinib
      resistant OE19 (OE19 LR) cells showed increased basal autophagic flux compared to
      parental OE19 (OE19 P) cells. Based on these results, we tested if combining
      Lapatinib with autophagy inhibitors might be beneficial. OE19 P showed
      significantly reduced cell viability upon double treatment, while OE19 LR were
      already sensitive to autophagy inhibition alone. Additionally, Her2 status and
      autophagy marker expression (LC3B and p62) were investigated in a treatment-naive
      EAC patient cohort (n = 112) using immunohistochemistry. Here, no significant
      correlation between Her2 status and expression of LC3B and p62 was found. Our
      data show that resistance to Her2-directed therapy is associated with a higher
      basal autophagy level, which is not per se associated with Her2 status.
      Therefore, we propose that autophagy may contribute to acquired resistance to
      Her2-targeted therapy in EAC, and that combining Her2 and autophagy inhibition
      might be beneficial for EAC patients.

PMID- 30297651
TI  - A Simulation Study Using Terrestrial LiDAR Point Cloud Data to Quantify Spectral
      Variability of a Broad-Leaved Forest Canopy.
AB  - In this analysis, a method for construction of forest canopy three-dimensional
      (3D) models from terrestrial LiDAR was used for assessing the influence of
      structural changes on reflectance for an even-aged forest in Belgium. The
      necessary data were extracted by the developed method, as well as it was
      registered the adjacent point-clouds, and the canopy elements were classified.
      Based on a voxelized approach, leaf area index (LAI) and the vertical
      distribution of leaf area density (LAD) of the forest canopy were derived. Canopy
      radiation interactions were simulated in a ray tracing environment, giving
      suitable illumination properties and optical attributes of the different canopy
      elements. Canopy structure was modified in terms of LAI and LAD for hyperspectral
      measurements. It was found that the effect of a 10% increase in LAI on NIR
      reflectance can be equal to change caused by translating 50% of leaf area from
      top to lower layers. As presented, changes in structure did affect vegetation
      indices associated with LAI and chlorophyll content. Overall, the work
      demonstrated the ability of terrestrial LiDAR for detailed canopy assessments and
      revealed the high complexity of the relationship between vertical LAD and
      reflectance.

PMID- 30297652
TI  - New 3-Hydroxyquinaldic Acid Derivatives from Cultures of the Marine Derived
      Actinomycete Streptomyces cyaneofuscatus M-157.
AB  - Fractionation of the bioactive extract of a culture of the marine derived
      actinomycete Streptomyces cyaneofuscatus M-157 led to the isolation of the known
      3-hydroxyquinaldic acid (4), its amide (5) and three new derivatives (1-3)
      containing different amino acid residues. The structures of the new molecules (1
      3), including their absolute configuration, were determined by the analysis of
      their ESI-TOF MS and one-dimensional (1D) and two-dimensional (2D) NMR spectra
      and advanced Marfey's analysis of their hydrolyzation products. Compound 3
      spontaneously dimerized in solution to give the disulfide derivative 6.
      Unfortunately, none of the new compounds isolated confirmed the antimicrobial
      activity found in the bacterial extract, perhaps indicating that such
      antibacterial activity might be due to presence in the extract at the trace level
      of larger bioactive 3-hydroxyquinaldic acid derivatives from which compounds 1-3
      are biosynthetic precursors. Cytotoxicity tests confirmed the moderate and weak
      IC50 values of 15.6 and 51.5 uM for compounds 5 and 1, respectively.

PMID- 30297653
TI  - New Method for Simultaneous Determination of Microcystins and Cylindrospermopsin
      in Vegetable Matrices by SPE-UPLC-MS/MS.
AB  - Cyanotoxins are a large group of noxious metabolites with different chemical
      structure and mechanisms of action, with a worldwide distribution, producing
      effects in animals, humans, and crop plants. When cyanotoxin-contaminated waters
      are used for the irrigation of edible vegetables, humans can be in contact with
      these toxins through the food chain. In this work, a method for the simultaneous
      detection of Microcystin-LR (MC-LR), Microcystin-RR (MC-RR), Microcystin-YR (MC
      YR), and Cylindrospermopsin (CYN) in lettuce has been optimized and validated,
      using a dual solid phase extraction (SPE) system for toxin extraction and ultra
      performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for
      analysis. Results showed linear ranges (5-50 ng g-1 f.w.), low values for limit
      of detection (LOD) (0.06-0.42 ng g-1 f.w.), and limit of quantification (LOQ)
      (0.16-0.91 ng g-1 f.w.), acceptable recoveries (41-93%), and %RSDIP values for
      the four toxins. The method proved to be robust for the three variables tested.
      Finally, it was successfully applied to detect these cyanotoxins in edible
      vegetables exposed to cyanobacterial extracts under laboratory conditions, and it
      could be useful for monitoring these toxins in edible vegetables for better
      exposure estimation in terms of risk assessment.

PMID- 30297655
TI  - The C-Reactive Protein/Albumin Ratio as a Predictor of Mortality in Critically
      Ill Patients.
AB  - The C-reactive protein (CRP)/albumin ratio has recently emerged as a marker for
      poor prognosis or mortality across various patient groups. This study aimed to
      identify the association between CRP/albumin ratio and 28-day mortality and
      predict the accuracy of CRP/albumin ratio for 28-day mortality in medical
      intensive care unit (ICU) patients. This was a retrospective cohort study of 875
      patients. We evaluated the prognostic value of CRP/albumin ratio to predict
      mortality at 28 days after ICU admission, using Cox proportional hazard model and
      Kaplan-Meier survival analysis. The 28-day mortality was 28.0%. In the univariate
      analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score
      (p < 0.001), CRP level (p = 0.045), albumin level (p < 0.001), and CRP/albumin
      ratio (p = 0.032) were related to 28-day mortality. The area under the receiver
      operating characteristic (ROC) curve (the area under the ROC curves (AUC)) of
      CRP/albumin ratio was higher than that of CRP for mortality (0.594 vs. 0.567, p <
      0.001). The cut-off point for CRP/albumin ratio for mortality was 34.3. On Cox
      proportional-hazard regression analysis, APACHE II score (hazards ratio (HR) =
      1.05, 95% confidence interval (CI) = 1.04-1.07, p < 0.001) and CRP/albumin ratio
      (HR = 1.68, 95% CI = 1.27-2.21, p < 0.001 for high CRP/albumin ratio) were
      independent predictors of 28-day mortality. Higher CRP/albumin ratio was
      associated with increased mortality in critically ill patients.

PMID- 30297654
TI  - Construction of Multiple Switchable Sensors and Logic Gates Based on Carboxylated
      Multi-Walled Carbon Nanotubes/Poly(N,N-Diethylacrylamide).
AB  - In this work, binary hydrogel films based on carboxylated multi-walled carbon
      nanotubes/poly(N,N-diethylacrylamide) (c-MWCNTs/PDEA) were successfully
      polymerized and assembled on a glassy carbon (GC) electrode surface. The
      electroactive drug probes matrine and sophoridine in solution showed reversible
      thermal-, salt-, methanol- and pH-responsive switchable cyclic voltammetric (CV)
      behaviors at the film electrodes. The control experiments showed that the pH
      responsive property of the system could be ascribed to the drug components of the
      solutions, whereas the thermal-, salt- and methanol-sensitive behaviors were
      attributed to the PDEA constituent of the films. The CV signals particularly, of
      matrine and sophoridine were significantly amplified by the electrocatalysis of c
      MWCNTs in the films at 1.02 V and 0.91 V, respectively. Moreover, the addition of
      esterase, urease, ethyl butyrate, and urea to the solution also changed the pH of
      the system, and produced similar CV peaks as with dilution by HCl or NaOH. Based
      on these experiments, a 6-input/5-output logic gate system and 2-to-1 encoder
      were successfully constructed. The present system may lead to the development of
      novel types of molecular computing systems.

PMID- 30297656
TI  - Salmon Fillet Intake Led to Higher Serum Triacylglycerol in Obese Zucker Fa/Fa
      Rats But Not in Normolipidemic Long-Evans Rats.
AB  - The triacylglycerol lowering effect of fatty fish and fish oils is well
      recognized, however we recently showed that salmon intake resulted in higher
      serum triacylglycerol concentration in obese Zucker fa/fa rats. Since effects of
      salmon fillet have never before been studied in rats, the objective of this study
      was to compare effects of salmon intake on serum lipids in hyperlipidemic obese
      rats with normolipidemic lean rats. Zucker fa/fa rats and Long-Evans rats were
      fed diets with 25% protein from baked salmon fillet and 75% protein from casein,
      or casein as sole protein source (control group) for four weeks. Serum
      triacylglycerol concentration was higher, and cholesterol and apolipoproteinB-100
      concentrations were lower in Zucker fa/fa rats fed Baked Salmon Diet compared to
      Zucker fa/fa rats fed Control Diet, with no differences in serum triacylglycerol,
      cholesterol and apolipoproteinB-100 between Long-Evans rats fed Baked Salmon Diet
      or Control Diet. Serum triacylglycerol fatty acid composition showed greater
      similarities to dietary fatty acids in Zucker fa/fa rats than in Long-Evans rats.
      To conclude, intake of baked salmon fillet resulted in higher serum
      triacylglycerol concentration and lower serum cholesterol concentration in
      hyperlipidemic obese Zucker fa/fa rats but did not affect serum lipids in
      normolipidemic lean Long-Evans rats.

PMID- 30297658
TI  - Characteristics of Graphene Oxide Films Reduced by Using an Atmospheric Plasma
      System.
AB  - The chemical oxidation method can be used to mass-produce graphene oxides (GOs)
      from highly oriented pyrolytic graphite. However, numerous oxygen-containing
      functional groups (hydroxyl, epoxy, carbonyl, etc.) exist in typical GO surfaces,
      resulting in serious electrical losses. Hence, GO must be processed into reduced
      graphene oxide (rGO) by the removal of most of the oxygen-containing functional
      groups. This research concentrates on the reduction efficiency of GO films that
      are manufactured using atmospheric-pressure and continuous plasma irradiation.
      Before and after sessions of plasma irradiation with various irradiation times,
      shelters, and working distances, the surface, physical, and electrical
      characteristics of homemade GO and rGO films are measured and analyzed.
      Experimental results showed that the sheet resistance values of rGO films with
      silicon or quartz shelters were markedly lower than those of GO films because the
      rGO films were mostly deprived of oxygen-containing functional groups. The lowest
      sheet resistance value and the largest carbon-to-oxygen ratio of typical rGO
      films were approximately 90 Omega/sq and 1.522, respectively. The intensity of
      the C-O bond peak in typical rGO films was significantly lower than that in GO
      films. Moreover, the intensity of the C-C bond peak in typical rGO films was
      considerably higher than that in GO films.

PMID- 30297657
TI  - Effects of Ag Additive in Low Temperature CO Detection with In2O3 Based Gas
      Sensors.
AB  - Nanocomposites In2O3/Ag obtained by ultraviolet (UV) photoreduction and
      impregnation methods were studied as materials for CO sensors operating in the
      temperature range 25-250  degrees C. Nanocrystalline In2O3 and In2O3/Ag
      nanocomposites were characterized by X-ray diffraction (XRD), single-point
      Brunauer-Emmet-Teller (BET) method, scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), and high angle annular dark field
      scanning transmission electron microscopy (HAADF-STEM) with energy dispersive X
      ray (EDX) mapping. The active surface sites were investigated using Fourier
      transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS),
      electron paramagnetic resonance (EPR) spectroscopy and thermo-programmed
      reduction with hydrogen (TPR-H2) method. Sensor measurements in the presence of
      15 ppm CO demonstrated that UV treatment leads to a complete loss of In2O3 sensor
      sensitivity, while In2O3/Ag-UV nanocomposite synthesized by UV photoreduction
      demonstrates an increased sensor signal to CO at T < 200  degrees C. The observed
      high sensor response of the In2O3/Ag-UV nanocomposite at room temperature may be
      due to the realization of an additional mechanism of CO oxidation with
      participation of surface hydroxyl groups associated via hydrogen bonds.

PMID- 30297659
TI  - An Evolutionary Game-Theoretic Approach for Assessing Privacy Protection in
      mHealth Systems.
AB  - With the rapid deployment of mobile technologies and their applications in the
      healthcare domain, privacy concerns have emerged as one of the most critical
      issues. Traditional technical and organizational approaches used to address
      privacy issues ignore economic factors, which are increasingly important in the
      investment strategy of those responsible for ensuring privacy protection. Taking
      the mHealth system as the context, this article builds an evolutionary game to
      model three types of entities (including system providers, hospitals and
      governments) under the conditions of incomplete information and bounded
      rationality. Given that the various participating entities are often unable to
      accurately estimate their own profits or costs, we propose a quantified approach
      to analyzing the optimal strategy of privacy investment and regulation. Numerical
      examples are provided for illustration and simulation purpose. Based upon these
      examples, several countermeasures and suggestions for privacy protection are
      proposed. Our analytical results show that governmental regulation and auditing
      has a significant impact on the strategic choice of the other two entities
      involved. In addition, the strategic choices of system providers and hospitals
      are not only correlated with profits and investment costs, but they are also
      significantly affected by free riding. If the profit growth coefficients increase
      to a critical level, mHealth system providers and hospitals will invest in
      privacy protection even without the imposition of regulations. However, the
      critical level is dependent on the values of the parameters (variables) in each
      case of investment and profits.

PMID- 30297660
TI  - Factors Associated with Early Mortality in Critically Ill Patients Following the
      Initiation of Continuous Renal Replacement Therapy.
AB  - Continuous renal replacement therapy (CRRT) is an important modality to support
      critically ill patients, and the need for CRRT treatment has been increasing.
      However, CRRT management is costly, and the associated resources are limited.
      Thus, it remains challenging to identify patients that are likely to have a poor
      outcome, despite active treatment with CRRT. We sought to elucidate the factors
      associated with early mortality after CRRT initiation. We analyzed 240 patients
      who initiated CRRT at an academic medical center between September 2016 and
      January 2018. We compared baseline characteristics between patients who died
      within seven days of initiating CRRT (early mortality), and those that survived
      more than seven days beyond the initiation of CRRT. Of the patients assessed, 130
      (54.2%) died within seven days of CRRT initiation. Multivariate logistic
      regression models revealed that low mean arterial pressure, low arterial pH, and
      high Sequential Organ Failure Assessment score before CRRT initiation were
      significantly associated with increased early mortality in patients requiring
      CRRT. In conclusion, the mortality within seven days following CRRT initiation
      was very high in this study. We identified several factors that are associated
      with early mortality in patients undergoing CRRT, which may be useful in
      predicting early outcomes, despite active treatment with CRRT.

PMID- 30297661
TI  - Chemical Components and Biological Activities of the Genus Phyllanthus: A Review
      of the Recent Literature.
AB  - Medicinal plants have served humans since prehistoric times to treat various
      ailments. Both developed and underdeveloped countries rely on traditional systems
      of medication using natural sources from plants. Phyllanthus is one of the
      largest genus in the family Phyllanthaceae, comprising over 700 well known
      species cosmopolitan in distribution mainly in the tropics and subtropics.
      Phyllanthus species are being in constant used in traditional medications to cure
      an array of human diseases (constipation, inhalation related, arthritis, loss of
      appetite, injuries, conjunctivitis, diarrhoea, running nose, common cold,
      malaria, blennorrhagia, colic, diabetes mellitus, dysentery, indigestion, fever,
      gout, gonorrheal diseases of males and females, skin itching, jaundice, hepatic
      disorders, leucorrhea, vaginitis, menstrual irregularities, obesity, stomach
      pains, and tumors), confectionaries, food industry, and in some pesticides.
      Phyllanthus species are rich in diversity of phytochemicals e.g., tannins,
      terpenes, alkaloids, glycosidic compounds, saponins, and flavones etc. More in
      depth studies are a direly needed to identify more compounds with specific
      cellular functions to treat various ailments.

PMID- 30297662
TI  - Human Dendritic Cells: Ontogeny and Their Subsets in Health and Disease.
AB  - Dendritic cells (DCs) are a type of cells derived from bone marrow that represent
      1% or less of the total hematopoietic cells of any lymphoid organ or of the total
      cell count of the blood or epithelia. Dendritic cells comprise a heterogeneous
      population of cells localized in different tissues where they act as sentinels
      continuously capturing antigens to present them to T cells. Dendritic cells are
      uniquely capable of attracting and activating naive CD4+ and CD8+ T cells to
      initiate and modulate primary immune responses. They have the ability to
      coordinate tolerance or immunity depending on their activation status, which is
      why they are also considered as the orchestrating cells of the immune response.
      The purpose of this review is to provide a general overview of the current
      knowledge on ontogeny and subsets of human dendritic cells as well as their
      function and different biological roles.

PMID- 30297664
TI  - Copaifera langsdorffii Novel Putative Long Non-Coding RNAs: Interspecies
      Conservation Analysis in Adaptive Response to Different Biomes.
AB  - Long non-coding RNAs (lncRNAs) are involved in multiple regulatory pathways and
      its versatile form of action has disclosed a new layer in gene regulation.
      LncRNAs have their expression levels modulated during plant development, and in
      response to stresses with tissue-specific functions. In this study, we analyzed
      lncRNA from leaf samples collected from the legume Copaifera langsdorffii Desf.
      (copaiba) present in two divergent ecosystems: Cerrado (CER; Ecological Station
      of Botanical Garden in Brasilia, Brazil) and Atlantic Rain Forest (ARF; Rio de
      Janeiro, Brazil). We identified 8020 novel lncRNAs, and they were compared to
      seven Fabaceae genomes and transcriptomes, to which 1747 and 2194 copaiba lncRNAs
      were mapped, respectively, to at least one species. The secondary structures of
      the lncRNAs that were conserved and differentially expressed between the
      populations were predicted using in silico methods. A few selected lncRNA were
      confirmed by RT-qPCR in the samples from both biomes; Additionally, the analysis
      of the lncRNA sequences predicted that some might act as microRNA (miRNA) targets
      or decoys. The emerging studies involving lncRNAs function and conservation have
      shown their involvement in several types of biotic and abiotic stresses. Thus,
      the conservation of lncRNAs among Fabaceae species considering their rapid
      turnover, suggests they are likely to have been under functional conservation
      pressure. Our results indicate the potential involvement of lncRNAs in the
      adaptation of C. langsdorffii in two different biomes.

PMID- 30297663
TI  - Effect of Low Dose Docosahexaenoic Acid-Rich Fish Oil on Plasma Lipids and
      Lipoproteins in Pre-Menopausal Women: A Dose-Response Randomized Placebo
      Controlled Trial.
AB  - Omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation has
      been shown to improve plasma lipid profiles in men and post-menopausal women,
      however, data for pre-menopausal women are lacking. The benefits of intakes less
      than 1 g/day have not been well studied, and dose-response data is limited. The
      aim of this study was to determine the effect of low doses of docosahexaenoic
      acid (DHA)-rich tuna oil on plasma triglyceride (TG) lowering in pre-menopausal
      women, and investigate if low dose DHA-rich tuna oil supplementation would
      increase the low-density lipoprotein (LDL) and high-density lipoprotein (HDL)
      particle sizes. A randomized, double-blind, placebo-controlled trial was
      conducted, in which 53 healthy pre-menopausal women with mildly elevated plasma
      TG levels consumed 0, 0.35, 0.7, or 1 g/day n-3 LCPUFA as HiDHATM tuna oil or
      placebo (Sunola oil) capsules for 8 weeks. Supplementation with 1 g/day n-3
      LCPUFA, but not lower doses, reduced plasma TG by 23% in pre-menopausal women.
      This was reflected in a dose-dependent reduction in very-low-density lipoprotein
      (VLDL)-TG (R2 = 0.20, p = 0.003). A weak dose-dependent shift in HDL (but not
      LDL) particle size was identified (R2 = 0.05, p = 0.04). The results of this
      study indicate that DHA-rich n-3 LCPUFA supplementation at a dose of 1 g/day is
      an effective TG-lowering agent and increases HDL particle size in pre-menopausal
      women.

PMID- 30297665
TI  - Effects of Laser Welding and Post-Weld Heat Treatment on Microstructure and
      Mechanical Properties of Aged Ti55531 Alloy.
AB  - As one of the relatively new titanium (Ti) alloys in the engineering field, beta
      Ti alloy-Ti55531 has attracted a great deal of attention due to its excellent
      mechanical properties, while a few research papers on weldability and the post
      weld heat treatment (PWHT) process of Ti55531 have been reported. Based on an
      orthogonal experiment design, the parameters of laser beam welding (LBW) of
      Ti55531 alloy with a thickness of 2 mm were optimized. Moreover, the influences
      of welding parameters and PWHT on the microstructures and performance of the
      laser-welded joint of Ti55531 were analyzed. The results showed that, for
      microstructures in different zones of as-welded joints of Ti55531: three forms of
      alpha phases (i.e., equiaxial alphap phase, lamellar alphaS phase, and alphaGB
      phase at grain boundaries) were observed in base metal (BM); in the heat affected
      zone (HAZ), part of lamellar alphaS phase had dissolved while equiaxial alphap
      phase had grown; the fusion zone (FZ) mainly consisted of beta phase, which
      presented as coarse columnar crystals. After the PWHT process, the
      microstructures of the welded joint were changed: in the BM zone, alpha phase at
      grain boundary disappeared and lamellar alpha phase decreased; in the HAZ, the
      edge of alphap phase obviously dissolved; in the FZ, plenty of compact needle
      like alpha phases were observed. The tensile strength of the as-welded joint was
      about 940 MPa and then increased to 1161 MPa after PWHT, which were 78.4% and
      96.8% of that of the original BM respectively. The fracture position transformed
      from the interface between the FZ and HAZ to the BM during tensile tests after
      PWHT.

PMID- 30297666
TI  - Unsupervised Machine Learning for Advanced Tolerance Monitoring of Wire
      Electrical Discharge Machining of Disc Turbine Fir-Tree Slots.
AB  - Manufacturing more efficient low pressure turbines has become a topic of primary
      importance for aerospace companies. Specifically, wire electrical discharge
      machining of disc turbine fir-tree slots has attracted increasing interest in
      recent years. However, important issues must be still addressed for optimum
      application of the WEDM process for fir-tree slot production. The current work
      presents a novel approach for tolerance monitoring based on unsupervised machine
      learning methods using distribution of ionization time as a variable. The need
      for time-consuming experiments to set-up threshold values of the monitoring
      signal is avoided by using K-means and hierarchical clustering. The developments
      have been tested in the WEDM of a generic fir-tree slot under industrial
      conditions. Results show that 100% of the zones classified into Clusters 1 and 2
      are related to short-circuit situations. Further, 100% of the zones classified in
      Clusters 3 and 5 lie within the tolerance band of +/-15 MUm. Finally, the 9
      regions classified in Cluster 4 correspond to situations in which the wire is
      moving too far away from the part surface. These results are strongly in accord
      with tolerance distribution as measured by a coordinate measuring machine.

PMID- 30297667
TI  - Analysis of Aggregate Morphological Characteristics for Viscoelastic Properties
      of Asphalt Mixes Using Simplex Lattice Design.
AB  - Morphological characteristics of aggregates have direct impacts on performances
      of asphalt mixes. This paper aims to investigate the effects of the morphological
      characteristics of fine and coarse aggregates on the high-temperature
      viscoelastic properties of asphalt mortars and mixtures. For this purpose, an
      experimental proportion scheme was designed for asphalt mixes prepared with three
      different types of aggregates (basalt, andesite and pebble/river sand) based on
      the simplex lattice design (SLD) method. Three morphological parameters were
      chosen to characterize shape, angularity and texture of aggregates. Afterwards,
      the uniaxial compression creep test was conducted for asphalt mixes and the high
      temperature viscoelastic properties were obtained based on Burgers model. The
      effects of fine and coarse aggregates on the viscoelastic properties are analyzed
      through asphalt mortars and mixtures, respectively. The results showed that
      aggregate morphological characteristics correlate with the high-temperature
      viscoelastic properties of asphalt mixes, especially for fine aggregates.
      Aggregates with complex morphological characteristics are conducive to improving
      the deformation recovery and anti-deformation of asphalt mixes. Furthermore,
      coarse aggregates can enhance the anti-deformation of asphalt mixture effectively
      due to its skeleton effect.

PMID- 30297668
TI  - Human Milk Oligosaccharides to Prevent Gut Dysfunction and Necrotizing
      Enterocolitis in Preterm Neonates.
AB  - This review focuses on the evidence for health benefits of human milk
      oligosaccharides (HMOs) for preterm infants to stimulate gut adaptation and
      reduce the incidence of necrotizing enterocolitis (NEC) in early life. The health
      benefits of breastfeeding are partly explained by the abundant HMOs that serve as
      prebiotics and immunomodulators. Gut immaturity in preterm infants leads to
      difficulties in tolerating enteral feeding and bacterial colonization and a high
      sensitivity to NEC, particularly when breast milk is insufficient. Due to the
      immaturity of the preterm infants, their response to HMOs could be different from
      that in term infants. The concentration of HMOs in human milk is highly variable
      and there is no evidence to support a specifically adapted high concentration in
      preterm milk. Further, the gut microbiota is not only different but also highly
      variable after preterm birth. Studies in pigs as models for preterm infants
      indicate that HMO supplementation to formula does not mature the gut or prevent
      NEC during the first weeks after preterm birth and the effects may depend on a
      certain stage of gut maturity. Supplemented HMOs may become more important for
      gut protection in the preterm infants when the gut has reached a more mature
      phase.

PMID- 30297669
TI  - The Inhibitory Effects of Cyclodepsipeptides from the Entomopathogenic Fungus
      Beauveria bassiana on Myofibroblast Differentiation in A549 Alveolar Epithelial
      Cells.
AB  - Pulmonary fibrosis (PF) is a chronic and fatal lung disease with few treatment
      options. Although the pathogenesis of PF is not clear, a chronic inflammatory
      response to continuous damage is considered the cause of pulmonary fibrosis. PF
      is characterized by excessive accumulation of extracellular matrix (ECM),
      therefore, inhibition of myofibroblast differentiation is a good therapeutic
      target for PF. As part of our continuing endeavor to explore biologically active
      metabolites from insect-associated microbes, we found that the MeOH extract of
      the culture broth from the entomopathogenic fungus Beauveria bassiana inhibited
      collagen induction and E-cadherin down-regulation. In order to identify active
      compounds, we carried out chemical analysis of the MeOH extract with the
      assistance of LC/MS-guided isolation approach, which led to the successful
      identification of four cyclodepsipeptides 1-4. Among the isolates, compound 2
      showed inhibitory effects on myofibroblast differentiation induced by TGF-beta1.
      Compound 2 inhibited induction of alpha-SMA and N-cadherin, which are
      myofibroblast markers, and blocked the accumulation of ECM proteins such as
      collagen and fibronectin. Overall these findings demonstrate that compound 2 can
      be used to attenuate pulmonary fibrosis by targeting myo- fibroblast
      differentiation.

PMID- 30297670
TI  - Diffusivities and Atomic Mobilities in bcc Ti-Mo-Zr Alloys.
AB  - beta-type (with bcc structure) titanium alloys have been widely used as
      artificial implants in the medical field due to their favorable properties. Among
      them, Ti-Mo alloy attracted numerous interests as metallic biomaterials.
      Understanding of kinetic characteristics of Ti alloys is critical to understand
      and manipulate the phase transformation and microstructure evolution during
      homogenization and precipitation. In this work, diffusion couple technique was
      employed to investigate the diffusion behaviors in bcc Ti-Mo-Zr alloys. The
      diffusion couples were prepared and annealed at 1373 K for 72 h and 1473 K for 48
      h, respectively. The composition-distance profiles were obtained via electron
      probe micro-analysis (EPMA). The chemical diffusion coefficients and impurity
      diffusion coefficients were extracted via the Whittle-Green method and Hall
      method. The obtained diffusion coefficients were assessed to develop a self
      consistent atomic mobility database of bcc phase in Ti-Mo-Zr system. The
      calculated diffusion coefficients were compared with the experimental results.
      They showed good agreement. Simulations were implemented by Dictra Module in
      Thermo-Calc software. The predicted composition-distance profiles, inter
      diffusion flux, and diffusion paths are consistent with experimental data,
      confirming the accuracy of the database.

PMID- 30297671
TI  - One-Step Fabrication of Three-Dimensional Fibrous Collagen-Based Macrostructure
      with High Water Uptake Capability by Coaxial Electrospinning.
AB  - One step fabrication of the three dimension (3D) fibrous structure of Collagen-g
      poly(MMA-co-EA)/Nylon6 was investigated by controlling the experimental
      conditions during coaxial electrospinning. This 3D fibrous structure is the
      result of interactions of two polymeric systems with a varied capability to be
      electrostatically polarized under the influence of the external electric field;
      the solution with the higher conductivity into the inner spinneret and the
      solution with the lesser conductivity into the outer capillary of the coaxial
      needle. This set-up was to obtain bimodal fiber fabrication in micro and
      nanoscale developing a spatial structure; the branches growing off a trunk. The
      resultant 3D collagen-based fibrous structure has two distinguished
      configurations: microfibers of 6.9 +/- 2.2 um diameter gap-filled with nanofibers
      of 216 +/- 49 nm diameter. The 3D fibrous structure can be accumulated at an
      approximate height of 4 cm within 20 min. The mechanism of the 3D fibrous
      structure and the effect of experimental conditions, the associated hydration
      degree, water uptake and degradation rate were also investigated. This highly
      stable 3D fibrous structure has great potential end-uses benefitting from its
      large surface area and high water uptake which is caused by the high polarity and
      spatial orientation of collagen-based macrostructure.

PMID- 30297673
TI  - Decentralized Cooperative Localization with Fault Detection and Isolation in
      Robot Teams.
AB  - Robot localization, particularly multirobot localization, is an important task
      for multirobot teams. In this paper, a decentralized cooperative localization
      (DCL) algorithm with fault detection and isolation is proposed to estimate the
      positions of robots in mobile robot teams. To calculate the interestimate
      correlations in a distributed manner, the split covariance intersection filter
      (SCIF) is applied in the algorithm. Based on the split covariance intersection
      filter cooperative localization (SCIFCL) algorithm, we adopt fault detection and
      isolation (FDI) to improve the robustness and accuracy of the DCL results. In the
      proposed algorithm, the signature matrix of the original FDI algorithm is
      modified for application to DCL. A simulation-based comparative study is
      conducted to demonstrate the effectiveness of the proposed algorithm.

PMID- 30297675
TI  - Ceramide Synthase 6: Comparative Analysis, Phylogeny and Evolution.
AB  - Ceramide synthase 6 (CerS6, also known as LASS6) is one of the six members of
      ceramide synthase gene family in humans. Comparisons of CerS6 amino acid
      sequences and structures as well as of CerS6 gene structures/locations were
      conducted using data from several vertebrate genome projects. A specific role for
      the CerS6 gene and protein has been identified as the endoplasmic reticulum C14-
      and C16-ceramide synthase. Mammalian CerS6 proteins share 90-100% similarity
      among different species, but are only 22-63% similar to other CerS family
      members, suggesting that CerS6 is a distinct gene family. Sequence alignments,
      predicted transmembrane, lumenal and cytoplasmic segments and N-glycosylation
      sites were also investigated, resulting in identification of the key conserved
      residues, including the active site as well as C-terminus acidic and serine
      residues. Mammalian CerS6 genes contain ten exons, are primarily located on the
      positive strands and transcribed as two major isoforms. The human CERS6 gene
      promoter harbors a large CpG island (94 CpGs) and multiple transcription factor
      binding sites (TFBS), which support precise transcriptional regulation and
      signaling functions. Additional regulation is conferred by 15 microRNA (miRNA)
      target sites identified in the CERS6 3'-UTR region. Phylogenetic analysis of the
      vertebrate CerS1-6 gene families relationships supports a major role for the
      CerS6 enzyme that is strongly conserved throughout vertebrate evolution.

PMID- 30297674
TI  - Fabrication and Characterization of Strontium-Substituted Hydroxyapatite-CaO
      CaCO3 Nanofibers with a Mesoporous Structure as Drug Delivery Carriers.
AB  - Hydroxyapatite (HAp) is the main inorganic component and an essential part of
      hard bone and teeth. Due to its excellent biocompatibility, bioactivity, and
      osteoconductivity, synthetic HAp has been widely used as a bone substitute, cell
      carrier, and therapeutic gene or drug carrier. Recently, numerous studies have
      demonstrated that strontium-substituted hydroxyapatite (SrHAp) not only enhances
      osteogenesis but also inhibits adipogenesis in mesenchymal stem cells. Mesoporous
      SrHAp has been successfully synthesized via a traditional template-based process
      and has been found to possess better drug loading and release efficiencies than
      SrHAp. In this study, strontium-substituted hydroxyapatite-CaO-CaCO3 nanofibers
      with a mesoporous structure (mSrHANFs) were fabricated using a sol-gel method
      followed by electrospinning. X-ray diffraction analysis revealed that the
      contents of CaO and CaCO3 in the mSrHANFs decreased as the doping amount of Sr
      increased. Scanning electron microscopy (SEM) images showed that the average
      diameter of the mSrHANFs was approximately 200~300 nm. The N2 adsorption
      desorption isotherms demonstrated that the mSrHANFs possessed a mesoporous
      structure and that the average pore size was approximately 20~25 nm. Moreover,
      the mSrHANFs had excellent drug- loading efficiency and could retard the burst
      release of tetracycline (TC) to maintain antibacterial activity for over 3 weeks.
      Hence, mSrHANFs have the potential to be used as drug carriers in bone tissue
      engineering.

PMID- 30297672
TI  - Proteoglycans Are Attractive Biomarkers and Therapeutic Targets in Hepatocellular
      Carcinoma.
AB  - Proteoglycans, which consist of a protein core and glycosaminoglycan chains, are
      major components of the extracellular matrix and play physiological roles in
      maintaining tissue homeostasis. In the carcinogenic tissue microenvironment,
      proteoglycan expression changes dramatically. Altered proteoglycan expression on
      tumor and stromal cells affects cancer cell signaling pathways, which alters
      growth, migration, and angiogenesis and could facilitate tumorigenesis. This
      dysregulation of proteoglycans has been implicated in the pathogenesis of
      diseases such as hepatocellular carcinoma (HCC) and the underlying mechanism has
      been studied extensively. This review summarizes the current knowledge of the
      roles of proteoglycans in the genesis and progression of HCC. It focuses on well
      investigated proteoglycans such as serglycin, syndecan-1, glypican 3, agrin,
      collagen XVIII/endostatin, versican, and decorin, with particular emphasis on the
      potential of these factors as biomarkers and therapeutic targets in HCC regarding
      the future perspective of precision medicine toward the "cure of HCC".

PMID- 30297677
TI  - Degradation of the In-plane Shear Modulus of Structural BFRP Laminates Due to
      High Temperature.
AB  - The behavior of fiber reinforced polymer (FRP) composites at high temperature is
      a critical issue that needs to be clearly understood for their structural uses in
      civil engineering. However, due to technical difficulties during testing at high
      temperature, limited experimental investigations have been conducted regarding
      the thermal behavior of basalt fiber reinforced polymer (BFRP) composites,
      especially for the in-plane shear modulus of BFRP laminates. To this end, both an
      analytical derivation and an experimental program were carried out in this work
      to study the in-plane shear modulus of BFRP laminates. After the analytical
      derivation, the in-plane shear modulus was investigated as a function of the
      elastic modulus in different directions (0 degrees , 45 degrees  and 90 degrees 
      of the load-to-fiber angle) and Poisson's ratio in the fiber direction. To obtain
      the in-plane shear modulus, the four parameters were tested at different
      temperatures from 20 to 250  degrees C. A novel non-contacting digital image
      correlation (DIC) sensing system was adopted in the high-temperature tests to
      measure the local strain field on the FRP samples. Based on the test results, it
      was found that the elastic moduli in different directions were reduced to a very
      low level (less than 20%) from 20 to 250  degrees C. Furthermore, the in-plane
      shear modulus of BFRP at 250  degrees C was only 3% of that at 20  degrees C.

PMID- 30297676
TI  - Comparative RNA-Seq Analysis of High- and Low-Oil Yellow Horn During Embryonic
      Development.
AB  - Yellow horn (Xanthoceras sorbifolium Bunge) is an endemic oil-rich shrub that has
      been widely cultivated in northern China for bioactive oil production. However,
      little is known regarding the molecular mechanisms that contribute to oil content
      in yellow horn. Herein, we measured the oil contents of high- and low-oil yellow
      horn embryo tissues at four developmental stages and investigated the global gene
      expression profiles through RNA-seq. The results found that at 40, 54, 68, and 81
      days after anthesis, a total of 762, 664, 599, and 124 genes, respectively, were
      significantly differentially expressed between the high- and low-oil lines. Gene
      ontology (GO) enrichment analysis revealed some critical GO terms related to oil
      accumulation, including acyl-[acyl-carrier-protein] desaturase activity, pyruvate
      kinase activity, acetyl-CoA carboxylase activity, and seed oil body biogenesis.
      The identified differentially expressed genes also included several transcription
      factors, such as, AP2-EREBP family members, B3 domain proteins and C2C2-Dof
      proteins. Several genes involved in fatty acid (FA) biosynthesis,
      glycolysis/gluconeogenesis, and pyruvate metabolism were also up-regulated in the
      high-oil line at different developmental stages. Our findings indicate that the
      higher oil accumulation in high-oil yellow horn could be mostly driven by
      increased FA biosynthesis and carbon supply, i.e. a source effect.

PMID- 30297678
TI  - Early Life Professional and Layperson Support Reduce Poor Oral Hygiene Habits in
      Toddlers-A Prospective Birth Cohort Study.
AB  - Oral health behaviours of children are formulated from a very young age.
      Formation of those behaviours among very young children is dependent on their
      mothers/caregivers who may themselves require support from the health profession
      or laypersons. The study aimed to investigate if early life visits for check-up
      and dental advice and perceived support improved oral health behaviours as
      practiced by mothers of toddlers aged 24-30 months old. Data from a population
      base birth cohort study in South Australia was used. The study recruited and
      followed mothers of newborn children from birth to age 24-30 months. Parental
      questionnaires collected information about socioeconomic factors, dental visiting
      patterns, and oral health behaviours as practiced by the mothers for their child.
      Self-reported putting a child to bed with a bottle and brushing a child's teeth
      were the outcome variables. The two main exposures of this study were (1) early
      visiting for a dental advice, and (2) layperson support that a mother received in
      the first two years of having the child. Data were analysed progressively from
      bivariate to multivariable regression models. A total of 1183 mother/child dyads
      had complete data. The retained sample was representative of the population.
      Approximately 36% of mothers put their child to bed with a bottle and 26% of
      mothers did not brush their child's teeth the night before. Around 29% of
      children had a visit for dental check-up and 80% of mothers reported having lay
      support. There were gradients in the outcome variables by socioeconomic factors
      and the main exposures. Multivariable regression models reported that having no
      dental visit for advice and having no lay support were associated with 1.30 and
      1.21 imes higher rates of putting a child to bed with a bottle, respectively.
      Having no dental visit for advice was associated with a 1.37-times higher rate of
      not brushing a child's teeth, controlling for other factors. This population
      based birth cohort study confirmed importance of early life dental visit for
      check-up and support for mothers of young children in establishing oral health
      behaviours of young children.

PMID- 30297680
TI  - Beamforming Design for Full-Duplex SWIPT with Co-Channel Interference in Wireless
      Sensor Systems.
AB  - The simultaneous wireless information and power transfer (SWIPT) technique has
      been regarded as an appealing approach to prolong the lifetime of wireless sensor
      networks. However, co-channel interferences with SWIPT in wireless networks have
      not been investigated from a green communication perspective. In this paper,
      joint transmit and receive beamforming design for a full-duplex multiple-input
      multiple-output amplify-and-forward relay system with simultaneous wireless
      information and power transfer in WSNs is investigated. Multiple co-channel
      interferers are considered at the relay and destination sensor nodes. To minimize
      the mean-squared-error of the system, joint source and relay beamforming
      optimization is proposed while guaranteeing the transmit power constraints and
      destination's energy harvesting constraint. An iterative algorithm based on
      alternating optimization with successive convex approximation which converges to
      a local optimum is proposed to solve the non-convex problem. Moreover, a low
      complexity scheme is derived to reduce the computational complexity. Simulations
      for MSE versus iterations and MSE versus signal-to-noise ratio (SNR) demonstrate
      the convergence and good performance of the proposed schemes.

PMID- 30297679
TI  - Differential and Overlapping Effects of 20,23(OH)2D3 and 1,25(OH)2D3 on Gene
      Expression in Human Epidermal Keratinocytes: Identification of AhR as an
      Alternative Receptor for 20,23(OH)2D3.
AB  - A novel pathway of vitamin D activation by CYP11A has previously been elucidated.
      To define the mechanism of action of its major dihydroxy-products, we tested the
      divergence and overlap between the gene expression profiles of human epidermal
      keratinocytes treated with either CYP11A1-derived 20,23(OH)2D3 or classical
      1,25(OH)2D3. Both secosteroids have significant chemical similarity with the only
      differences being the positions of the hydroxyl groups. mRNA was isolated and
      examined by microarray analysis using Illumina's HumanWG-6 chip/arrays and
      subsequent bioinformatics analyses. Marked differences in the up- and
      downregulated genes were observed between 1,25(OH)2D3- and 20,23(OH)2D3-treated
      cells. Hierarchical clustering identified both distinct, opposite and common
      (overlapping) gene expression patterns. CYP24A1 was a common gene strongly
      activated by both compounds, a finding confirmed by qPCR. Ingenuity pathway
      analysis identified VDR/RXR signaling as the top canonical pathway induced by
      1,25(OH)2D3. In contrast, the top canonical pathway induced by 20,23(OH)2D3 was
      AhR, with VDR/RXR being the second nuclear receptor signaling pathway identified.
      QPCR analyses validated the former finding by revealing that 20,23(OH)2D3
      stimulated CYP1A1 and CYP1B1 gene expression, effects located downstream of AhR.
      Similar stimulation was observed with 20(OH)D3, the precursor to 20,23(OH)2D3, as
      well as with its downstream metabolite, 17,20,23(OH)3D3. Using a Human AhR
      Reporter Assay System we showed marked activation of AhR activity by
      20,23(OH)2D3, with weaker stimulation by 20(OH)D3. Finally, molecular modeling
      using an AhR LBD model predicted vitamin D3 hydroxyderivatives to be good ligands
      for this receptor. Thus, our microarray, qPCR, functional studies and molecular
      modeling indicate that AhR is the major receptor target for 20,23(OH)2D3, opening
      an exciting area of investigation on the interaction of different vitamin D3
      hydroxyderivatives with AhR and the subsequent downstream activation of signal
      transduction pathways in a cell-type-dependent manner.

PMID- 30297681
TI  - Pharmacokinetic, Antiproliferative and Apoptotic Effects of Phenolic Acids in
      Human Colon Adenocarcinoma Cells Using In Vitro and In Silico Approaches.
AB  - Colon cancer is the second most common cause of cancer deaths in the USA and
      Europe. Despite aggressive therapies, many tumors are resistant to current
      treatment protocols and epidemiological data suggest that diet is a major factor
      in the etiology of colon cancer. This study aimed to evaluate the antioxidant
      activity and the influence of 3,4-dihydroxyphenylacetic (3,4-DHPAA), p-coumaric
      (p-CoA), vanillic (VA) and ferulic (FA) acids on cell viability, cell cycle
      progression, and rate of apoptosis in human colon adenocarcinoma cells (HT-29).
      The results showed that all compounds tested reduce cell viability in human colon
      cancer cells. 3,4-DHPAA promoted the highest effect antiproliferative with an
      increase in the percentage of cells in G0/G1 phase, accompanied by a reduction of
      cells in G2/M phase. Cell cycle analysis of VA and FA showed a decrease in the
      proportion of cells in G0/G1 phase (10.0 uM and 100.0 uM). p-CoA and FA acids
      increased the percentage of apoptotic cells and non-apoptotic cells. 3,4-DHPAA
      seems to be the substance with the greatest potential for in vivo studies,
      opening thus a series of perspectives on the use of these compounds in the
      prevention and treatment of colon cancer.

PMID- 30297682
TI  - Importance of Mineral Nutrition for Mitigating Aluminum Toxicity in Plants on
      Acidic Soils: Current Status and Opportunities.
AB  - Aluminum (Al) toxicity is one of the major limitations that inhibit plant growth
      and development in acidic soils. In acidic soils (pH < 5.0), phototoxic-aluminum
      (Al3+) rapidly inhibits root growth, and subsequently affects water and nutrient
      uptake in plants. This review updates the existing knowledge concerning the role
      of mineral nutrition for alleviating Al toxicity in plants to acid soils. Here,
      we explored phosphorus (P) is more beneficial in plants under P-deficient, and Al
      toxic conditions. Exogenous P addition increased root respiration, plant growth,
      chlorophyll content, and dry matter yield. Calcium (Ca) amendment (liming) is
      effective for correcting soil acidity, and for alleviating Al toxicity. Magnesium
      (Mg) is able to prevent Al migration through the cytosolic plasma membrane in
      root tips. Sulfur (S) is recognized as a versatile element that alleviates
      several metals toxicity including Al. Moreover, silicon (Si), and other
      components such as industrial byproducts, hormones, organic acids, polyamines,
      biofertilizers, and biochars played promising roles for mitigating Al toxicity in
      plants. Furthermore, this review provides a comprehensive understanding of
      several new methods and low-cost effective strategies relevant to the exogenous
      application of mineral nutrition on Al toxicity mitigation. This information
      would be effective for further improvement of crop plants in acid soils.

PMID- 30297685
TI  - Attenuation of Morphine Withdrawal Syndrome by Prosopis Farcta Extract and Its
      Bioactive Component Luteolin in Comparison with Clonidine in Rats.
AB  - BACKGROUND Today, the plant Prosopis farcta is frequently used for traditional
      medicinal purposes. The aim of this study was the identification of luteolin in
      P. farcta extract (PFE) and to evaluate its effect on morphine discontinuation
      syndrome in rats. MATERIAL AND METHODS Using high-performance liquid
      chromatography (HPCL), luteolin was evaluated in PFE. The frequency of behavioral
      symptoms of morphine withdrawal (jumping, rearing, and teeth chattering) induced
      by naloxone challenge were illustrated in morphine-dependent rats receiving PFE,
      luteolin, saline, or clonidine. LD50 of PFE and luteolin was 540 mg/kg and 150
      mg/kg, respectively. Signs of behavioral morphine withdrawal in rats were
      significantly inhibited by chronic co-administration of PFE, luteolin, or
      clonidine with morphine. RESULTS This study showed that PFE was less effective
      than clonidine at a dose of 100 mg/kg, and at doses of 200 mg/kg and 300 mg/kg it
      was comparable to clonidine, and did not show a significant difference in the
      reduction of morphine withdrawal symptoms. Luteolin was comparable in 30 mg/kg,
      60 mg/kg, and 90 mg/kg with clonidine to reduce the frequency of morphine
      withdrawal symptoms. PFE can be used as a source of luteolin. CONCLUSIONS The
      study findings suggest that PFE and luteolin might reduce the signs of narcotic
      withdrawal. Due to a similar effect to clonidine, its mechanism of action might
      be through the protein kinase A pathway and might have human therapeutic
      potential.

PMID- 30297684
TI  - Supplementary Light Source Affects the Growth and Development of Codonopsis
      lanceolata Seedlings.
AB  - Codonopsis lanceolata is widely used in traditional medicine and diets. However,
      there is no optimal protocol for the commercial production of C. lanceolata
      seedlings. This study was carried out to find the optimum supplementary light
      source for the production of C. lanceolata seedlings. Seedlings were grown for
      four weeks in a glasshouse with an average daily light intensity of 490 MUmol.m
      2.s-1 photosynthetic photon flux density (PPFD) coming from the sun and a 16-h
      daily supplementary lighting at 120 MUmol.m-2.s-1 PPFD from either high-pressure
      sodium (HPS), metal halide (MH), far-red (FR), white LED (LED-w), or mixed
      (white: red: blue = 1:2:1) LEDs (LED-mix). The results showed that the greatest
      total biomass, stem diameter, ratio of shoot weight to shoot length, root
      biomass, and ratio of root weight to shoot weight were found in seedlings grown
      under supplementary LED-mix. Meanwhile, the stomatal properties and soluble sugar
      contents were improved for seedlings in LED-mix. The contents of starch, total
      phenols, and flavonoids were the greatest for seedlings in LED-w and LED-mix. The
      expression of photosynthetic proteins and genes in seedlings was also enhanced by
      LED-mix. Overall, these results suggest that LED-mix is advantageous to the
      photosynthetic potential and the accumulation of biomass, carbohydrates and
      secondary metabolites in C. lanceolata.

PMID- 30297683
TI  - Heat-Shock-Induced Removal of Transgenes Using the Gene-Deletor System in Hybrid
      Aspen (Populus tremula * P. tremuloides).
AB  - To evaluate the efficacy of the gene-deletor system in aspen, we evaluated the
      system for foreign gene removal in a hybrid aspen clone, INRA 353-53 (Populus
      tremula * P. tremuloides). The recombinase flipping DNA (FLP) gene was under the
      control of the heat-inducible promoter of Gmhsp17.6-L, and the beta-glucuronidase
      (gusA) gene which was under the control of the 35S promoter and were constructed
      using the gene-deletor system in the pCaLFGmFNLFG vector. Six transgenic plants
      and their sublines were heated at 42  degrees C for 8 h and gene deletion was
      verified by polymerase chain reaction (PCR). Three lines exhibited partial
      transgene deletion while the remaining three lines did not delete. Transgenic
      lines were evaluated by Southern-blot analyses, verifying that the six transgenic
      plant lines all had a single copy of transfer DNA (t-DNA). Two partial-deletion
      lines and two non-deletion lines were analysed for methylation and expression of
      promoter and recombinase. Hardly any methylation was detected in the Gmhsp17.6-L
      promoter or recombinase FLP gene sequences, however, the expression of the
      promoter and recombinase was increased significantly in the partial-deletion
      compared with the non-deletion line after heat-shock treatment. These results
      suggest that the excision efficiency had no direct relationship with methylation
      status of the Gmhsp17.6-L promoter and FLP recombinase, yet was affected by the
      expression of the Gmhsp17.6-L and FLP after heat-shock treatment.

PMID- 30297686
TI  - Risk Factors of Acute Rejection in Patients with BK Nephropathy After Reduction
      of Immunosuppression.
AB  - BACKGROUND BK nephropathy (BKN) affects graft function and increases the risk of
      graft failure. The reduction of immunosuppression is the main treatment for BKN.
      However, acute rejection may develop following immunosuppression reduction, and
      data regarding the risk factors of acute rejection during the post-reduction
      period are insufficient. MATERIAL AND METHODS Of 758 patients who received a
      kidney transplantation (KT) between 2008 and 2011, 79 who underwent
      immunosuppression reduction as BKN treatment were enrolled. The risk factors of
      acute rejection after immunosuppression reduction were identified using
      multivariate logistic regression analysis. RESULTS During the median follow-up
      period (75 months), acute rejection developed in 21.5% of study group patients
      and in 22.5% of KT recipients without BKN. The rejection group showed a trend of
      higher body mass index (24.13+/-3.92 vs. 22.40+/-3.31 kg/m2, P=0.070) and lower
      tacrolimus levels than the no rejection group, although mycophenolate mofetil
      (MMF) doses were not lower in the rejection group. The rejection group showed
      worse graft survival than the no rejection group (P=0.001 by the log rank test).
      A greater number of patients in the rejection group exhibited reduced calcineurin
      inhibitor (CNI) level by >20% at 1 month after initial BKV detection (34.2% vs.
      7.9%, P=0.008). Multivariate analysis indicated that the peak BKV PCR level (odds
      ratio [OR], 0.136; 95% confidence interval [CI], 0.025-0.732; P=0.020), MMF
      discontinuation (vs. MMF reduction; OR, 0.112; 95% CI, 0.020-0.618; P=0.012) and
      CNI level reduction >20% (OR, 33.752; 95% CI, 4.263-267.251; P=0.001) were
      significantly associated with acute rejection. CONCLUSIONS Acute rejection after
      immunosuppression reduction for BKN showed worse allograft survival than the
      patients without acute rejection. In addition, a CNI dose reduction >20% at 1
      month after the initial BKV detection can increase the risk of acute rejection.

PMID- 30297687
TI  - Clinical Value and Diagnostic Accuracy of 3.0T Multi-Parameter Magnetic Resonance
      Imaging in Traumatic Brachial Plexus Injury.
AB  - BACKGROUND The aim of this study was to evaluate the clinical value and
      diagnostic accuracy of 3.0T multi-parameter magnetic resonance imaging (MRI) in
      traumatic brachial plexus injury. MATERIAL AND METHODS Twenty-five healthy
      volunteers and 28 patients with clinically confirmed traumatic brachial plexus
      injury were enrolled in this study. Bilateral brachial plexus imaging was
      performed using conventional sequences (T1WI, T2WI), short time inversion
      recovery (STIR), balanced fast field echo (balance-FFE), and diffusion weighted
      imaging with background suppression (DWIBS). The MRI diagnosis was compared with
      intraoperative electromyography and surgery. RESULTS Brachial plexus injuries
      were classified based on the anatomic locations. There were 16 patients with pre
      ganglionic injury and 12 patients with post-ganglionic injury. The pre-ganglionic
      injury included ruptured nerve roots, stiff nerve roots, traumatic meningeal
      cysts, black line sign, spinal cord edema, and thickened nerve root sleeve. The
      post-ganglionic injury included thickened nerve roots, disappearance of normal
      nerve root structure or disrupted continuity of the nerve, stiff nerve roots,
      pseudo-neuroma, and abnormalities in the adjacent soft tissues. Comparing the
      results from MRI and surgery, the sensitivity, specificity, and accuracy of MRI
      examination were 93.55%, 71.43%, and 89.47% respectively for preganglionic
      injury, and 91.30%, 60.00%, and 85.71% respectively for postganglionic injury.
      CONCLUSIONS The combination of STIR, balance-FFE, and DWIBS sequences can display
      brachial plexus pre-ganglionic and post-ganglionic injury clearly, effectively,
      and accurately.

PMID- 30297688
TI  - Paradoxical Bronchoconstriction with Short-Acting Beta Agonist.
AB  - : BACKGROUND Asthma is a common disease in the U.S. POPULATION: Initial therapy
      in the stepwise approach for asthma management is short-acting beta2-agonist
      (SABA) therapy as needed for symptom control. However, a significant adverse
      event that can occur with administration is bronchospasm. Here, we report a case
      of paradoxical bronchospasm with administration of SABAs during multiple
      pulmonary function tests (PFTs). CASE REPORT A 25-year-old, non-smoking, African
      American male with a history of moderate asthma and allergic rhinitis treated
      with fluticasone/salmeterol diskus, albuterol hydrofluoroalkane (HFA) inhaler,
      and montelukast presented to our clinic complaining of recurrent episodes of
      acute shortness of breath immediately following each administration of albuterol
      for 4 weeks. PFTs were performed with levalbuterol (Xopenex) and albuterol
      (ProAir), yielding significant decrease in forced expiratory volume in 1 second
      (FEV1) and forced vital capacity (FVC). Nebulized albuterol and ipratropium
      bromide also improved FEV1 and FVC. He was successfully transitioned to an
      ipratropium rescue inhaler for asthma exacerbations. CONCLUSIONS Paradoxical
      bronchoconstriction is the unexpected constriction of smooth muscle walls of the
      bronchi that occurs in the setting of an expected bronchodilatory response. This
      phenomenon has been observed with beta2-agonist-containing inhaler formulations
      and is an under-recognized adverse event. Theories suggest that the formulation
      excipients can trigger airway hyperresponsiveness in patients with allergically
      inflamed airways. Removal of excipients or use of anticholinergic inhalers
      improved respiratory function. Clinicians should be aware of paradoxical
      bronchospasm as an adverse effect with common inhaler formulations containing
      beta2-agonists and counsel patients accordingly in the appropriate clinical
      setting.

PMID- 30297689
TI  - A sulfotransferase dosage-dependently regulates mouthpart polyphenism in the
      nematode Pristionchus pacificus.
AB  - Polyphenism, the extreme form of developmental plasticity, is the ability of a
      genotype to produce discrete morphologies matched to alternative environments.
      Because polyphenism is likely to be under switch-like molecular control, a
      comparative genetic approach could reveal the molecular targets of plasticity
      evolution. Here we report that the lineage-specific sulfotransferase SEUD-1,
      which responds to environmental cues, dosage-dependently regulates polyphenism of
      mouthparts in the nematode Pristionchus pacificus. SEUD-1 is expressed in cells
      producing dimorphic morphologies, thereby integrating an intercellular signalling
      mechanism at its ultimate target. Additionally, multiple alterations of seud-1
      support it as a potential target for plasticity evolution. First, a recent
      duplication of seud-1 in a sister species reveals a direct correlation between
      genomic dosage and polyphenism threshold. Second, inbreeding to produce divergent
      polyphenism thresholds resulted in changes in transcriptional dosage of seud-1.
      Our study thus offers a genetic explanation for how plastic responses evolve.

PMID- 30297690
TI  - Bacterial coinfection restrains antiviral CD8 T-cell response via LPS-induced
      inhibitory NK cells.
AB  - Infection of specific pathogen-free mice with lymphocytic choriomeningitis virus
      (LCMV) is a widely used model to study antiviral T-cell immunity. Infections in
      the real world, however, are often accompanied by coinfections with unrelated
      pathogens. Here we show that in mice, systemic coinfection with E. coli
      suppresses the LCMV-specific cytotoxic T-lymphocyte (CTL) response and virus
      elimination in a NK cell- and TLR2/4-dependent manner. Soluble TLR4 ligand LPS
      also induces NK cell-mediated negative CTL regulation during LCMV infection. NK
      cells in LPS-treated mice suppress clonal expansion of LCMV-specific CTLs by a
      NKG2D- or NCR1-independent but perforin-dependent mechanism. These results
      suggest a TLR4-mediated immunoregulatory role of NK cells during viral-bacterial
      coinfections.

PMID- 30297691
TI  - Modulation of proteoglycan receptor PTPsigma enhances MMP-2 activity to promote
      recovery from multiple sclerosis.
AB  - Multiple Sclerosis (MS) is characterized by focal CNS inflammation leading to the
      death of oligodendrocytes (OLs) with subsequent demyelination, neuronal
      degeneration, and severe functional deficits. Inhibitory chondroitin sulfate
      proteoglycans (CSPGs) are increased in the extracellular matrix in the vicinity
      of MS lesions and are thought to play a critical role in myelin regeneration
      failure. We here show that CSPGs curtail remyelination through binding with their
      cognate receptor, protein tyrosine phosphatase sigma (PTPsigma) on
      oligodendrocyte progenitor cells (OPCs). We report that inhibition of
      CSPG/PTPsigma signaling by systemically deliverable Intracellular Sigma Peptide
      (ISP), promotes OPC migration, maturation, remyelination, and functional recovery
      in animal models of MS. Furthermore, we report a downstream molecular target of
      PTPsigma modulation in OPCs involving upregulation of the protease MMP-2 that
      allows OPCs to enzymatically digest their way through CSPGs. In total, we
      demonstrate a critical role of PTPsigma/CSPG interactions in OPC remyelination in
      MS.

PMID- 30297693
TI  - Combined computational and experimental investigation of high temperature
      thermodynamics and structure of cubic ZrO2 and HfO2.
AB  - Structure and thermodynamics of pure cubic ZrO2 and HfO2 were studied
      computationally and experimentally from their tetragonal to cubic transition
      temperatures (2311 and 2530  degrees C) to their melting points (2710 and 2800 
      degrees C). Computations were performed using automated ab initio molecular
      dynamics techniques. High temperature synchrotron X-ray diffraction on laser
      heated aerodynamically levitated samples provided experimental data on volume
      change during tetragonal-to-cubic phase transformation (0.55 +/- 0.09% for ZrO2
      and 0.87 +/- 0.08% for HfO2), density and thermal expansion. Fusion enthalpies
      were measured using drop and catch calorimetry on laser heated levitated samples
      as 55 +/- 7 kJ/mol for ZrO2 and 61 +/- 10 kJ/mol for HfO2, compared with 54 +/- 2
      and 52 +/- 2 kJ/mol from computation. Volumetric thermal expansion for cubic ZrO2
      and HfO2 are similar and reach (4 +/- 1).10-5/K from experiment and (5 +/- 1).10
      5/K from computation. An agreement with experiment renders confidence in values
      obtained exclusively from computation: namely heat capacity of cubic HfO2 and
      ZrO2, volume change on melting, and thermal expansion of the liquid to 3127 
      degrees C. Computed oxygen diffusion coefficients indicate that above 2400 
      degrees C pure ZrO2 is an excellent oxygen conductor, perhaps even better than
      YSZ.

PMID- 30297692
TI  - Designed synthesis of stable light-emitting two-dimensional sp2 carbon-conjugated
      covalent organic frameworks.
AB  - Covalent organic frameworks enable the topological connection of organic
      chromophores into pi lattices, making them attractive for creating light-emitting
      polymers that are predesignable for both the primary- and high-order structures.
      However, owing to linkages, covalent organic frameworks are either unstable or
      poor luminescent, leaving the practical synthesis of stable light-emitting
      frameworks challenging. Here, we report the designed synthesis of sp2 carbon
      conjugated frameworks that combine stability with light-emitting activity. The
      C=C linkages topologically connect pyrene knots and arylyenevinylene linkers into
      two-dimensional all sp2 carbon lattices that are designed to be pi conjugated
      along both the x and y directions and develop layer structures, creating
      exceptionally stable frameworks. The resulting frameworks are capable of tuning
      band gap and emission by the linkers, are highly luminescent under various
      conditions and can be exfoliated to produce brilliant nanosheets. These results
      suggest a platform based on sp2 carbon frameworks for designing robust
      photofunctional materials.

PMID- 30297694
TI  - TIP55, a splice isoform of the KAT5 acetyltransferase, is essential for
      developmental gene regulation and organogenesis.
AB  - Regulation of chromatin structure is critical for cell type-specific gene
      expression. Many chromatin regulatory complexes exist in several different forms,
      due to alternative splicing and differential incorporation of accessory subunits.
      However, in vivo studies often utilize mutations that eliminate multiple forms of
      complexes, preventing assessment of the specific roles of each. Here we examined
      the developmental roles of the TIP55 isoform of the KAT5 histone
      acetyltransferase. In contrast to the pre-implantation lethal phenotype of mice
      lacking all four Kat5 transcripts, mice specifically deficient for Tip55 die
      around embryonic day 11.5 (E11.5). Prior to developmental arrest, defects in
      heart and neural tube were evident in Tip55 mutant embryos. Specification of
      cardiac and neural cell fates appeared normal in Tip55 mutants. However, cell
      division and survival were impaired in heart and neural tube, respectively,
      revealing a role for TIP55 in cellular proliferation. Consistent with these
      findings, transcriptome profiling revealed perturbations in genes that function
      in multiple cell types and developmental pathways. These findings show that Tip55
      is dispensable for the pre- and early post-implantation roles of Kat5, but is
      essential during organogenesis. Our results raise the possibility that isoform
      specific functions of other chromatin regulatory proteins may play important
      roles in development.

PMID- 30297695
TI  - Quinoa whole grain diet compromises the changes of gut microbiota and colonic
      colitis induced by dextran Sulfate sodium in C57BL/6 mice.
AB  - A plethora of evidence highlights that the dysbiosis of gut microbiota is a
      critical factor for inflammatory bowel disease (IBD). Both in vivo and in vitro
      studies have demonstrated that quinoa possesses potential prebiotic effects. The
      present study aims to examine the potential in using quinoa to ameliorate the
      dysbiosis and colitis induced by dextran sodium sulfate (DSS). A total of 40
      C57BL/6 mice were fed either an AIN-93M diet or a quinoa-based diet, separately.
      Colitis was induced for 10 animals/dietary group with a 5-days exposure to 2.5%
      DSS. The clinical symptoms were monitored every other day, and the gut microbiota
      was characterized by 16S rRNA gene sequencing. The results indicated that
      consumption of quinoa lessened clinical symptoms as indicated by the reduced
      disease activity index and the degree of histological damage (P < 0.05). As
      expected, the DSS treatment induced significant dysbiosis of gut microbiota in
      mice on an AIN-93M diet. However, compared to mice fed the AIN-93M diet, the
      consumption of quinoa alleviated the DSS-induced dysbiosis remarkably, as
      indicated by increased species richness and diversity, decreased abnormal
      expansion of phylum Proteobacteria, and decreased overgrowth of genera
      Escherichia/Shigella and Peptoclostridium (P < 0.05). The relative abundances of
      Firmicutes and Bacteroidetes were less altered in mice fed with quinoa comparing
      to those mice fed the AIN-93M diet. In summary, the consumption of quinoa
      suppressed the dysbiosis of gut microbiota and alleviated clinical symptoms
      induced by DSS, indicating the potential to utilize quinoa as a dietary approach
      to improve intestinal health.

PMID- 30297696
TI  - Tender leaf and fully-expanded leaf exhibited distinct cuticle structure and wax
      lipid composition in Camellia sinensis cv Fuyun 6.
AB  - The goal of the present study was to compare the structural and compositional
      differences of cuticle between tender leaf and fully-expanded leaf in Camellia
      sinensis, and provide metabolic base for the further characterization of wax
      biosynthesis in this economically important crop species. The tender second leaf
      and the fully-expanded fifth leaf from new twig were demonstrated to represent
      two different developmental stages, their cuticle thickness were measured by
      transmission electron microscopy. The thickness of the adaxial cuticle on the
      second and fifth leaf was 1.15 um and 2.48 um, respectively; the thickness of the
      abaxial cuticle on the second and fifth leaf was 0.47 um and 1.05 um,
      respectively. The thickness of the epicuticular wax layer from different leaf
      position or different sides of same leaf were similar. However, the
      intracuticular wax layer of the fifth leaf was much thicker than that of the
      second leaf. Total wax lipids were isolated from the second leaf and the fifth
      leaf, respectively. Gas chromatography-mass spectrometry analysis identified 51
      wax constituents belonging to 13 chemical classes, including esters, glycols,
      terpenoids, fatty acids and their derivatives. Wax coverage on the second and
      fifth leaf was 4.76 ug/cm2 and 15.38 ug/cm2, respectively. Primary alcohols
      dominated in the tender second leaf. However, triterpenoids were the major
      components from the fully-expanded fifth leaf. The predominant carbon chains
      varied depending on chemical class. These data showed that the wax profiles of
      Camellia sinensis leaves are development stage dependent, suggesting distinct
      developmental dependent metabolic pathways and regulatory mechanisms.

PMID- 30297698
TI  - Venous thromboembolism laboratory testing (factor V Leiden and factor II
      c.*97G>A), 2018 update: a technical standard of the American College of Medical
      Genetics and Genomics (ACMG).
AB  - Factor V Leiden and factor II c.*97G>A (formerly referred to as prothrombin
      20210G>A) are the two most common genetic variants associated with venous
      thromboembolism (VTE). Testing for these variants is one of the most common
      referrals in clinical genetics laboratories. While the methodologies for testing
      these two variants are relatively straightforward, the clinical implementation
      can be complicated with regard to test indications, risk assessment of occurrence
      and recurrence of VTE, and related genetic counseling. This document provides an
      overview of VTE, information about the variants and their influence on risk,
      considerations before initiating genetic testing, and the clinical and analytical
      sensitivity and specificity of the tests. Key information that should be included
      in the laboratory report is also provided. Disease-specific statements are
      intended to augment the general American College of Medical Genetics and Genomics
      (ACMG) technical standards for clinical genetics laboratories. Individual
      laboratories are responsible for meeting the Clinical Laboratory Improvement
      Amendments (CLIA)/College of American Pathologists (CAP) quality assurance
      standards with respect to appropriate sample documentation, assay validation,
      general proficiency testing, and quality control measures. This 2018 edition of
      the ACMG technical standard updates and supersedes the 2005 edition on this
      topic. It is designed to be a checklist for genetic testing professionals who are
      already familiar with the disease and the methods of analysis.

PMID- 30297697
TI  - Aberrant neuronal differentiation is common in glioma but is associated neither
      with epileptic seizures nor with better survival.
AB  - The mechanisms of glioma-associated seizures (GAS) have yet to be fully
      elucidated. Proneural subtype, isocitrate dehydrogenase 1 (IDH1) mutations, and
      epileptic seizures are closely associated suggesting that aberrant neuronal
      differentiation contributes to glioma-associated seizures. In a population-based
      cohort (n = 236), lack of stem cell marker expression (nestin, musashi) was
      significantly associated with IDH1 mutations and GAS at diagnosis. In vitro data
      suggested an association of IDH1 mutations and a more differentiated phenotype.
      Out of eight glioma stem cell (GSC) lines, seven revealed positivity for the
      synaptic marker protein synaptophysin. Three had synapse-like structures
      identified by electron microscopy and were either vGlut1 (glutamatergic) or GAD67
      (GABAergic) positive. In vivo, >10% synaptophysin-positive tumour cells were
      present in >90% of all gliomas. Synaptophysin expression was associated with
      proneural subtype and vGlut1 expression, suggesting that most synapse-like
      structures in glioma are glutamatergic. However, we found null associations
      between vGlut1 protein/mRNA expression and survival, GAS at onset, development of
      GAS after resection, and refractory GAS. Synapse-like structures were neither
      functional nor activated by spontaneous action potentials or cellular networks.
      Thus, aberrant neuronal differentiation including glutamatergic synapse-like
      structures is detectable in glioma but is associated neither with epileptic
      seizures nor with better survival.

PMID- 30297699
TI  - Correction: Mapping the genomic landscape of inherited retinal disease genes
      prioritizes genes prone to coding and noncoding copy-number variations.
AB  - The original version of this Article contained an error in the spelling of the
      author Anja K. Mayer, which was incorrectly given as Anja Kathrin Mayer. This has
      now been corrected in both the PDF and HTML versions of the Article.

PMID- 30297700
TI  - Biomechanical Evaluation of Wasp and Honeybee Stingers.
AB  - In order to design a painless and mechanically durable micro syringe-needle
      system for biomedical applications, the study of insect stingers is of interest
      because of their elegant structures and functionalities. In the present work, the
      structure, mechanical properties and the mechanical behavior during insertion of
      wasp and honeybee stingers have been investigated. The non-invasive imaging tool,
      micro-computed tomography has been employed to reveal the 3D-structures of wasp
      and honeybee stingers. A quasi-static nanoindentation instrument was used to
      measure the nanomechanical properties. Both wasp and honeybee stingers have
      graded mechanical properties, decreasing along their longitudinal direction
      starting from the base. The computed tomography images and the measured material
      properties from nanoindentation were fed into a computational framework to
      determine the mechanical behavior of the stingers during penetration. The
      computation results predicted the penetration angle of +10 degrees  for the wasp
      stinger and -6 degrees  for the honeybee stinger, which mimics the practical
      insertion mechanism of both stingers. Based on this understanding, a wasp and
      honeybee stringer inspired micro syringe-needle design has also been proposed.

PMID- 30297702
TI  - Elevated expression of a minor isoform of ANK3 is a risk factor for bipolar
      disorder.
AB  - Ankyrin-3 (ANK3) is one of the few genes that have been consistently identified
      as associated with bipolar disorder by multiple genome-wide association studies.
      However, the exact molecular basis of the association remains unknown. A rare
      loss-of-function splice-site SNP (rs41283526*G) in a minor isoform of ANK3
      (incorporating exon ENSE00001786716) was recently identified as protective of
      bipolar disorder and schizophrenia. This suggests that an elevated expression of
      this isoform may be involved in the etiology of the disorders. In this study, we
      used novel approaches and data sets to test this hypothesis. First, we strengthen
      the statistical evidence supporting the allelic association by replicating the
      protective effect of the minor allele of rs41283526 in three additional large
      independent samples (meta-analysis p-values: 6.8E-05 for bipolar disorder and
      8.2E-04 for schizophrenia). Second, we confirm the hypothesis that both bipolar
      and schizophrenia patients have a significantly higher expression of this isoform
      than controls (p-values: 3.3E-05 for schizophrenia and 9.8E-04 for bipolar type
      I). Third, we determine the transcription start site for this minor isoform by
      Pacific Biosciences sequencing of full-length cDNA and show that it is primarily
      expressed in the corpus callosum. Finally, we combine genotype and expression
      data from a large Norwegian sample of psychiatric patients and controls, and show
      that the risk alleles in ANK3 identified by bipolar disorder GWAS are located
      near the transcription start site of this isoform and are significantly
      associated with its elevated expression. Together, these results point to the
      likely molecular mechanism underlying ANK3's association with bipolar disorder.

PMID- 30297701
TI  - Blood-based biomarkers for Alzheimer disease: mapping the road to the clinic.
AB  - Biomarker discovery and development for clinical research, diagnostics and
      therapy monitoring in clinical trials have advanced rapidly in key areas of
      medicine - most notably, oncology and cardiovascular diseases - allowing rapid
      early detection and supporting the evolution of biomarker-guided, precision
      medicine-based targeted therapies. In Alzheimer disease (AD), breakthroughs in
      biomarker identification and validation include cerebrospinal fluid and PET
      markers of amyloid-beta and tau proteins, which are highly accurate in detecting
      the presence of AD-associated pathophysiological and neuropathological changes.
      However, the high cost, insufficient accessibility and/or invasiveness of these
      assays limit their use as viable first-line tools for detecting patterns of
      pathophysiology. Therefore, a multistage, tiered approach is needed, prioritizing
      development of an initial screen to exclude from these tests the high numbers of
      people with cognitive deficits who do not demonstrate evidence of underlying AD
      pathophysiology. This Review summarizes the efforts of an international working
      group that aimed to survey the current landscape of blood-based AD biomarkers and
      outlines operational steps for an effective academic-industry co-development
      pathway from identification and assay development to validation for clinical use.

PMID- 30297703
TI  - Biosynthetic energy cost for amino acids decreases in cancer evolution.
AB  - Rapidly proliferating cancer cells have much higher demand for proteinogenic
      amino acids than normal cells. The use of amino acids in human proteomes is
      largely affected by their bioavailability, which is constrained by the
      biosynthetic energy cost in living organisms. Conceptually distinct from gene
      based analyses, we introduce the energy cost per amino acid (ECPA) to
      quantitatively characterize the use of 20 amino acids during protein synthesis in
      human cells. By analyzing gene expression data from The Cancer Genome Atlas, we
      find that cancer cells evolve to utilize amino acids more economically by
      optimizing gene expression profile and ECPA shows robust prognostic power across
      many cancer types. We further validate this pattern in an experimental evolution
      of xenograft tumors. Our ECPA analysis reveals a common principle during cancer
      evolution.

PMID- 30297704
TI  - Author Correction: Scutoids are a geometrical solution to three-dimensional
      packing of epithelia.
AB  - The original version of this Article contained an error in ref. 39, which
      incorrectly cited 'Fristrom, D. & Fristrom, J. W. in The Development of
      Drosophila melanogaster (eds. Bate, M. & Martinez-Arias, A.) II, (Cold spring
      harbor laboratory press, 1993)'. The correct reference is 'Condic, M.L, Fristrom,
      D. & Fristrom, J.W. Apical cell shape changes during Drosophila imaginal leg disc
      elongation: a novel morphogenetic mechanism. Development 111: 23-33 (1991)'.
      Furthermore, the last sentence of the fourth paragraph of the introduction
      incorrectly omitted citation of work by Rupprecht et al. The correct citation is
      given below. These errors have now been corrected in both the PDF and HTML
      versions of the Article. Rupprecht, J.F., Ong, K.H., Yin, J., Huang, A., Dinh,
      H.H., Singh, A.P., Zhang, S., Yu, W. & Saunders, T.E. Geometric constraints alter
      cell arrangements within curved epithelial tissues. Mol. Biol. Cell 28, 3582-3594
      (2017).

PMID- 30297705
TI  - beta2-Adrenergic receptor modulates mitochondrial metabolism and disease
      progression in recurrent/metastatic HPV(+) HNSCC.
AB  - The incidence of human papillomavirus-associated head and neck squamous cell
      carcinoma (HPV[ + ] HNSCC) is rapidly increasing. Although clinical management of
      primary HPV( + ) HNSCC is relatively successful, disease progression, including
      recurrence and metastasis, is often fatal. Moreover, patients with progressive
      disease face limited treatment options and significant treatment-associated
      morbidity. These clinical data highlight the need to identify targetable
      mechanisms that drive disease progression in HPV( + ) HNSCC to prevent and/or
      treat progressive disease. Interestingly, beta-adrenergic signaling has recently
      been associated with pro-tumor processes in several disease types. Here we show
      that an aggressive murine model of recurrent/metastatic HPV( + ) HNSCC
      upregulates beta2-adrenergic receptor (beta2AR) expression, concordant with
      significantly heightened mitochondrial metabolism, as compared with the parental
      model from which it spontaneously derived. beta-Adrenergic blockade effectively
      inhibits in vitro proliferation and migratory capacity in this model, effects
      associated with an attenuation of hyperactive mitochondrial respiration.
      Importantly, propranolol, a clinically available nonselective beta-blocker,
      significantly slows primary tumor growth, inhibits metastatic development, and
      shows additive benefit alongside standard-of-care modalities in vivo. Further,
      via CRISPR/Cas9 technology, we show that the hyperactive mitochondrial metabolic
      profile and aggressive in vivo phenotype of this recurrent/metastatic model are
      dependent on beta2AR expression. These data implicate beta2AR as a modulator of
      mitochondrial metabolism and disease progression in HPV( + ) HNSCC, and warrant
      further investigation into the use of beta-blockers as low cost, relatively
      tolerable, complementary treatment options in the clinical management of this
      disease.

PMID- 30297706
TI  - Transplantation of a bone marrow mesenchymal stem cell line increases neuronal
      progenitor cell migration in a cerebral ischemia animal model.
AB  - Mesenchymal stem cell (MSC) transplantation is demonstrated to improve functional
      and pathological recovery in cerebral ischemia. To understand the underlying
      mechanism, we transplanted a MSC line (B10) in a rat middle cerebral artery
      occlusion (MCAO) model and checked the proliferation and migration of neuronal
      progenitor cells (NPCs). B10 transplantation increased NPCs in the subventricular
      zone and their migration towards the lesion area at an earlier time. Fourteen
      days after MCAO, some NPCs were differentiated to neurons and astrocytes.
      Although B10 transplantation increased total number of both astrocytes and
      neurons, it only increased the differentiation of NPC to astrocyte. The mRNA of
      polysialylation enzyme ST8SiaIV and a chemokine SDF-1 were persistently increased
      in B10-transplanted groups. SDF-1-positive cell number was increased in the core
      and penumbra area, which was expressed in macrophage/microglia and transplanted
      B10 cells at 3 days after MCAO. Furthermore, SDF-1 mRNA expression in cell
      culture was high in B10 compared to a microglia (HMO) or a neuronal (A1) cell
      line. B10 culture supernatant increased in vitro A1 cell migration, which was
      significantly inhibited by siRNA-mediated SDF-1 silencing in B10. Thus, our
      results suggested that MSC transplantation increased endogenous NPC migration in
      cerebral ischemic condition by increasing chemokine and polysialylation enzyme
      expression, which could be helpful for the restorative management of cerebral
      ischemia.

PMID- 30297707
TI  - Maintaining and breaking symmetry in homomeric coiled-coil assemblies.
AB  - In coiled-coil (CC) protein structures alpha-helices wrap around one another to
      form rope-like assemblies. Most natural and designed CCs have two-four helices
      and cyclic (Cn) or dihedral (Dn) symmetry. Increasingly, CCs with five or more
      helices are being reported. A subset of these higher-order CCs is of interest as
      they have accessible central channels that can be functionalised; they are alpha
      helical barrels. These extended cavities are surprising given the drive to
      maximise buried hydrophobic surfaces during protein folding and assembly in
      water. Here, we show that alpha-helical barrels can be maintained by the
      strategic placement of beta-branched aliphatic residues lining the lumen.
      Otherwise, the structures collapse or adjust to give more-complex multi-helix
      assemblies without Cn or Dn symmetry. Nonetheless, the structural hallmark of CCs
      namely, knobs-into-holes packing of side chains between helices-is maintained
      leading to classes of CCs hitherto unobserved in nature or accessed by design.

PMID- 30297708
TI  - Sequencing HIV-neutralizing antibody exons and introns reveals detailed aspects
      of lineage maturation.
AB  - The developmental pathways of broadly neutralizing antibodies (bNAbs) against HIV
      are of great importance for the design of immunogens that can elicit protective
      responses. Here we show the maturation features of the HIV-neutralizing anti-V1V2
      VRC26 lineage by simultaneously sequencing the exon together with the downstream
      intron of VRC26 members. Using the mutational landscapes of both segments and the
      selection-free nature of the intron region, we identify multiple events of amino
      acid mutational convergence in the complementarity-determining region 3 (CDR3) of
      VRC26 members, and determine potential intermediates with diverse CDR3s to a late
      stage bNAb from 2 years prior to its isolation. Moreover, we functionally
      characterize the earliest neutralizing intermediates with critical CDR3
      mutations, with some emerging only 14 weeks after initial lineage detection and
      containing only ~6% V gene mutations. Our results thus underscore the utility of
      analyzing exons and introns simultaneously for studying antibody maturation and
      repertoire selection.

PMID- 30297709
TI  - Plantar cutaneous afferents influence the perception of Subjective Visual
      Vertical in quiet stance.
AB  - The estimation of Subjective Visual Vertical (SVV) involves the allocentric,
      gravitational and egocentric references, which are built by visual, vestibular
      and somatosensory afferents. Our goals were to assess the influence of plantar
      cutaneous afferents on the perception of SVV, and to see if there is a difference
      according to the efficiency of plantar cutaneous afferents. We recruited 48 young
      and healthy subjects and assessed their SVV and postural performances in quiet
      stance with a force platform, at 40 or 200 cm, in four ground conditions: on firm
      ground, on foam, with a bilateral, or with a unilateral 3 mm arch support. We
      also assessed the efficiency of our subjects' plantar afferents with the plantar
      quotient method and divided them in two groups: subjects with a normal use of
      plantar afferents and subjects with Plantar Exteroceptive Inefficiency (PEI). The
      results showed significant decreases in the counter clockwise SVV deviation only
      with the unilateral arch support, at near distance, and among the typically
      behaving subjects. We conclude that asymmetric foot cutaneous afferents are able
      to bias the egocentric vertical reference and hence influence the perception of
      SVV. This influence disappears among subjects with PEI, probably because of a
      distortion of the plantar signal.

PMID- 30297710
TI  - Author Correction: Large intrinsic anomalous Hall effect in half-metallic
      ferromagnet Co3Sn2S2 with magnetic Weyl fermions.
AB  - The original version of this Article incorrectly omitted an affiliation of
      Hongming Weng: "Beijing National Laboratory for Condensed Matter Physics and
      Institute of Physics, Chinese Academy of Sciences, 100190, Beijing, China"This
      has been corrected in both the PDF and HTML versions of the Article.

PMID- 30297711
TI  - Seasonal modulation of deep slow-slip and earthquakes on the Main Himalayan
      Thrust.
AB  - The interaction between seasonally-induced non-tectonic and tectonic deformation
      along the Himalayan plate boundary remains debated. Here, we propose that
      tectonic deformation along this plate boundary can be significantly influenced by
      the deformation induced by the non-tectonic hydrological loading cycles. We
      explore seasonal mass oscillations by continental water storage in Southeast Asia
      and Himalayan arc region using continuous Global Positioning System measurements
      and satellite data from the Gravity Recovery and Climate Experiment. We suggest
      that the substantially higher transient displacements above the base of the
      seismogenic zone indicate a role of changes in aseismic slip rate on the deep
      megathrust that may be controlled by seasonal hydrological loading. We invoke
      modulation of aseismic slip on the megathrust down-dip of the seismogenic zone
      due to a fault resonance process induced by the seasonal stress changes. This
      process modulates mid-crustal ramp associated micro-seismicity and influences the
      timing of Central Himalayan earthquakes.

PMID- 30297712
TI  - SWI/SNF catalytic subunits' switch drives resistance to EZH2 inhibitors in ARID1A
      mutated cells.
AB  - Inactivation of the subunits of SWI/SNF complex such as ARID1A is synthetically
      lethal with inhibition of EZH2 activity. However, mechanisms of de novo
      resistance to EZH2 inhibitors in cancers with inactivating SWI/SNF mutations are
      unknown. Here we show that the switch of the SWI/SNF catalytic subunits from
      SMARCA4 to SMARCA2 drives resistance to EZH2 inhibitors in ARID1A-mutated cells.
      SMARCA4 loss upregulates anti-apoptotic genes in the EZH2 inhibitor-resistant
      cells. EZH2 inhibitor-resistant ARID1A-mutated cells are hypersensitive to BCL2
      inhibitors such as ABT263. ABT263 is sufficient to overcome resistance to an EZH2
      inhibitor. In addition, ABT263 synergizes with an EZH2 inhibitor in vivo in
      ARID1A-inactivated ovarian tumor mouse models. Together, these data establish
      that the switch of the SWI/SNF catalytic subunits from SMARCA4 to SMARCA2
      underlies the acquired resistance to EZH2 inhibitors. They suggest BCL2
      inhibition alone or in combination with EZH2 inhibition represents urgently
      needed therapeutic strategy for ARID1A-mutated cancers.

PMID- 30297713
TI  - Adaptive effect of sericin on hepatic mitochondrial conformation through its
      regulation of apoptosis, autophagy and energy maintenance: a proteomics approach.
AB  - We recently demonstrated that in addition to its protective effect on pancreatic
      and adrenal biosynthesis, antioxidant properties of sericin decrease blood
      cholesterol levels and improve the liver mitochondrial architecture. However,
      little is known about the detailed mechanisms underlying these effects. Using
      proteomics and electron microscopy, we identified mitochondrial proteins that
      play important roles in the preservation of the mitochondrial ultrastructure and
      cholesterol-lowering properties of sericin. Our results showed that sericin
      maintains the mitochondrial architecture during conditions of high blood
      cholesterol by regulating apoptotic (NADH-ubiquinone oxidoreductase 75 kDa
      subunit) and autophagic (mitochondrial elongation factor Tu and prohibitin-2)
      proteins as well as energy maintenance proteins [haloacid dehalogenase-like
      hydrolase domain-containing protein 3, succinate dehydrogenase (ubiquinone)
      flavoprotein subunit, ATP synthase-alpha subunit precursor, enoyl-CoA hydratase
      domain-containing protein 3 and electron transfer flavoprotein subunit-alpha].
      Sericin also exerts anti-oxidative properties via aconitate hydratase and Chain
      A, crystal structure of rat carnitine palmitoyltrasferase 2 proteins. Together,
      these activities may reduce hepatocytic triglyceride deposition, thereby
      decreasing steatosis, as demonstrated by the modulatory effects on ornithine
      aminotransferase, mitochondrial aspartate aminotransferase, acyl-CoA synthase,
      hydroxyacyl-CoA dehydrogenase and D-beta-hydroxybutyrate dehydrogenase. Sericin
      activity further balanced nitrogenous waste detoxification, characterised by
      carbamoyl-phosphate synthase (ammonia), aldehyde dehydrogenase and uricase, or
      folate biosynthesis via sarcosine dehydrogenase and dimethyl glycine
      dehydrogenase. These results suggest that sericin maintains the hepatic
      mitochondrial architecture through apoptotic, autophagic, energy maintenance and
      anti-oxidative mitochondrial proteins for alleviating hepatic steatosis and
      promoting liver function under conditions of hypercholesterolaemia.

PMID- 30297714
TI  - Correction: The Type of Bariatric Surgery Impacts the Risk of Acute Pancreatitis:
      A Nationwide Study.
AB  - In the original version of this Article, a footnote was missing. The PDF and HTML
      versions of the Article have now been corrected to include the following: This
      study was presented as an abstract at the World Congress of Gastroenterology
      (WCOG) at ACG 2017, Orlando Florida.

PMID- 30297717
TI  - Statins as adjuvants.

PMID- 30297716
TI  - Time units for learning involving maintenance of system-wide cFos expression in
      neuronal assemblies.
AB  - Repeated experiences may be integrated in succession during a learning process,
      or they may be combined as a whole within dedicated time windows to possibly
      promote quality control. Here we show that in Pavlovian, incremental and
      incidental learning, related information acquired within time windows of 5 h is
      combined to determine what mice learn. Trials required for learning had to occur
      within 5 h, when learning-related shared cues could produce association and
      interference. Upon acquisition, cFos expression was elevated during 5 h
      throughout specific system-wide neuronal assemblies. Time window function
      depended on network activity and cFos expression. Local cFos activity was
      required for distant assembly recruitment through network activity and distant
      BDNF. Activation of learning-related cFos assemblies was sufficient and necessary
      for time window function. Therefore, learning processes consist of dedicated 5 h
      time windows (time units for learning), involving maintenance of system-wide
      neuronal assemblies through network activity and cFos expression.

PMID- 30297715
TI  - Matrix mechanical plasticity regulates cancer cell migration through confining
      microenvironments.
AB  - Studies of cancer cell migration have found two modes: one that is protease
      independent, requiring micron-sized pores or channels for cells to squeeze
      through, and one that is protease-dependent, relevant for confining nanoporous
      matrices such as basement membranes (BMs). However, many extracellular matrices
      exhibit viscoelasticity and mechanical plasticity, irreversibly deforming in
      response to force, so that pore size may be malleable. Here we report the impact
      of matrix plasticity on migration. We develop nanoporous and BM ligand-presenting
      interpenetrating network (IPN) hydrogels in which plasticity could be modulated
      independent of stiffness. Strikingly, cells in high plasticity IPNs carry out
      protease-independent migration through the IPNs. Mechanistically, cells in high
      plasticity IPNs extend invadopodia protrusions to mechanically and plastically
      open up micron-sized channels and then migrate through them. These findings
      uncover a new mode of protease-independent migration, in which cells can migrate
      through confining matrix if it exhibits sufficient mechanical plasticity.

PMID- 30297719
TI  - Stable and unstable regions of the Lorenz system.
AB  - The stable and unstable regions of the Lorenz system are studied. We discuss the
      relationship between the initial conditions and both these regions, specifically,
      the preference for the trajectory of the Lorenz system to move towards the left
      or right equilibrium-point region from an initial point and the residence time of
      a trajectory in an equilibrium-point region. For this purpose, the four-rank
      Runge-Kutta algorithms and mathematical derivations are used, whereas a
      statistical method for the residence times is used. We conclude that the stable
      and unstable regions are intrinsic to the Lorenz system and have no correlation
      with the initial conditions; indeed, these regions do not change given different
      initial conditions. The trajectory of the Lorenz system tends towards the left
      equilibrium-point region locally, with an average residence time of 8.74 but only
      5.789 for the right equilibrium-point region. In general, the system prefers the
      right equilibrium-point region for which the jump frequency of trajectories to
      the right region is 535 but only 465 to the left region from the initial
      conditions for the first time.

PMID- 30297718
TI  - Synergy between intrinsically disordered domains and structured proteins
      amplifies membrane curvature sensing.
AB  - The ability of proteins to sense membrane curvature is essential to cellular
      function. All known sensing mechanisms rely on protein domains with specific
      structural features such as wedge-like amphipathic helices and crescent-shaped
      BAR domains. Yet many proteins that contain these domains also contain large
      intrinsically disordered regions. Here we report that disordered domains are
      themselves potent sensors of membrane curvature. Comparison of Monte Carlo
      simulations with in vitro and live-cell measurements demonstrates that the
      polymer-like behavior of disordered domains found in endocytic proteins drives
      them to partition preferentially to convex membrane surfaces, which place fewer
      geometric constraints on their conformational entropy. Further, proteins
      containing both structured curvature sensors and disordered regions are more than
      twice as curvature sensitive as their respective structured domains alone. These
      findings demonstrate an entropic mechanism of curvature sensing that is
      independent of protein structure and illustrate how structured and disordered
      domains can synergistically enhance curvature sensitivity.

PMID- 30297720
TI  - Stable and discriminating features are predictive of cancer presence and Gleason
      grade in radical prostatectomy specimens: a multi-site study.
AB  - Site variation in fixation, staining, and scanning can confound automated tissue
      based image classifiers for disease characterization. In this study we
      incorporated stability into four feature selection methods for identifying the
      most robust and discriminating features for two prostate histopathology
      classification tasks. We evaluated 242 morphology features from N = 212
      prostatectomy specimens from four sites for automated cancer detection and
      grading. We quantified instability as the rate of significant cross-site feature
      differences. We mapped feature stability and discriminability using 188 non
      cancerous and 210 cancerous regions via 3-fold cross validation, then held one
      site out, creating independent training and testing sets. In training, one
      feature set was selected only for discriminability, another for discriminability
      and stability. We trained a classifier with each feature set, testing on the hold
      out site. Experiments were repeated with 117 Gleason grade 3 and 112 grade 4
      regions. Stability was calculated across non-cancerous regions. Gland shape
      features yielded the best stability and area under the receiver operating curve
      (AUC) trade-off while co-occurrence texture features were generally unstable. Our
      stability-informed method produced a cancer detection AUC of 0.98 +/- 0.05 and
      increased average Gleason grading AUC by 4.38%. Color normalization of the images
      tended to exacerbate feature instability.

PMID- 30297721
TI  - Visualising peripheral arterioles and venules through high-resolution and large
      area photoacoustic imaging.
AB  - Photoacoustic (PA) imaging (PAI) has been shown to be a promising tool for non
      invasive blood vessel imaging. A PAI system comprising a hemispherical detector
      array (HDA) has been reported previously as a method providing high morphological
      reproducibility. However, further improvements in diagnostic capability will
      require improving the image quality of PAI and fusing functional and
      morphological imaging. Our newly developed PAI system prototype not only enhances
      the PA image resolution but also acquires ultrasonic (US) B-mode images at
      continuous positions in the same coordinate axes. In addition, the pulse-to-pulse
      alternating laser irradiation shortens the measurement time difference between
      two wavelengths. We scanned extremities and breasts in an imaging region 140 mm
      in diameter and obtained 3D-PA images of fine blood vessels, including arterioles
      and venules. We could estimate whether a vessel was an artery or a vein by using
      the S-factor obtained from the PA images at two wavelengths, which corresponds
      approximately to the haemoglobin oxygen saturation. Furthermore, we observed
      tumour-related blood vessels around breast tumours with unprecedented resolution.
      In the future, clinical studies with our new PAI system will help to elucidate
      various mechanisms of vascular-associated diseases and events.

PMID- 30297722
TI  - Ginkgolide B promotes neuronal differentiation through the Wnt/beta-catenin
      pathway in neural stem cells of the postnatal mammalian subventricular zone.
AB  - Chinese herbal medicines (CHMs) have been used to treat human diseases for
      thousands of years. Among them, Ginkgo biloba is reported to be beneficial to the
      nervous system and a potential treatment of neurological disorders. Since the
      presence of adult neural stem cells (NSCs) brings hope that the brain may heal
      itself, whether the effect of Ginkgo biloba is on NSCs remains elusive. In this
      study, we found that Ginkgo biloba extract (GBE) and one of its main ingredients,
      ginkgolide B (GB) promoted cell cycle exit and neuronal differentiation in NSCs
      derived from the postnatal subventricular zone (SVZ) of the mouse lateral
      ventricle. Furthermore, the administration of GB increased the nuclear level of
      beta-catenin and activated the canonical Wnt pathway. Knockdown of beta-catenin
      blocked the neurogenic effect of GB, suggesting that GB promotes neuronal
      differentiation through the Wnt/beta-catenin pathway. Thus, our data provide a
      potential mechanism underlying the therapeutic effect of GBE or GB on brain
      injuries and neurodegenerative disorders.

PMID- 30297723
TI  - Chromosome replication as a measure of bacterial growth rate during Escherichia
      coli infection in the mouse peritonitis model.
AB  - The efficacy of most antibiotics is dependent on active bacterial growth, yet
      little is known about the growth dynamics during infection. Therefore, means to
      measure in-host bacterial growth rate is of importance. Here, we use chromosome
      replication as readout for in situ bacterial growth rate during infection;
      obtained from a single biological specimen. We have applied two independent
      methods: quantitative PCR (qPCR) and fluorescence microscopy, to quantify the
      level of chromosome replication present during Escherichia coli propagation in
      the mouse peritonitis model. We find that the methods complement each other and
      allow for quantification of growth rate, both on a population average and on a
      single-cell level. We demonstrate the presence of heterogeneous growth rates
      within bacterial populations propagating during infection. Also, no growth
      cessation was observed during the apparent stationary phase in vivo, and, by
      comparison of growth dynamics at different anatomical sites, we demonstrate that
      E. coli is unlikely to grow independently intravascularly. These findings provide
      novel insight into bacterial growth during host infection, and underscore the
      importance of pinpointing the primary site of infection in septicaemia of unknown
      origin and ensuring antibiotic availability at this site.

PMID- 30297724
TI  - Clinical usefulness of C-reactive protein to albumin ratio in predicting 30-day
      mortality in critically ill patients: A retrospective analysis.
AB  - This study aimed to examine the prognostic value of C-reactive protein
      (CRP)/albumin (ALB) ratio among patients who were admitted to the intensive care
      unit (ICU) in predicting 30-day mortality rate. This retrospective cohort study
      was conducted by examining the medical records of adult patients who were
      admitted to the ICU at Seoul National University Bundang Hospital between 1
      January 2012 and 31 December 2016. Data from 6,972 individuals were included in
      the final analysis, and 547 of these individuals (7.1%) died within 30 days after
      their ICU admission. The multivariable Cox regression analysis revealed that an
      increase of 1 for the CRP/ALB ratio was associated with an 11% increase in the
      risk of 30-day mortality (hazard ratio: 1.11, 95% confidence interval: 1.09-1.14,
      P < 0.001). However, the area under curve of CRP/ALB ratio in receiver operating
      characteristic analysis was lower than that of Acute Physiologic Assessment and
      Chronic Health Evaluation (APACHE) II, Charlson comorbidity index, or serum
      albumin alone. Although an elevated CRP/ALB ratio on ICU admission was an
      independent risk factor for 30-day mortality rate, the predictive power of
      CRP/ALB ratio was lower than that of albumin alone, APACHE II, and Charlson
      comorbidity index.

PMID- 30297725
TI  - The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is
      vital for ookinete formation and mosquito transmission.
AB  - Two members of 6-cysteine (6-cys) protein family, P48/45 and P230, are important
      for gamete fertility in rodent and human malaria parasites and are leading
      transmission blocking vaccine antigens. Rodent and human parasites encode a
      paralog of P230, called P230p. While P230 is expressed in male and female
      parasites, P230p is expressed only in male gametocytes and gametes. In rodent
      malaria parasites this protein is dispensable throughout the complete life-cycle;
      however, its function in P. falciparum is unknown. Using CRISPR/Cas9 methodology
      we disrupted the gene encoding Pfp230p resulting in P. falciparum mutants
      (PfDeltap230p) lacking P230p expression. The PfDeltap230p mutants produced normal
      numbers of male and female gametocytes, which retained expression of P48/45 and
      P230. Upon activation male PfDeltap230p gametocytes undergo exflagellation and
      form male gametes. However, male gametes are unable to attach to red blood cells
      resulting in the absence of characteristic exflagellation centres in vitro. In
      the absence of P230p, zygote formation as well as oocyst and sporozoite
      development were strongly reduced (>98%) in mosquitoes. These observations
      demonstrate that P230p, like P230 and P48/45, has a vital role in P. falciparum
      male fertility and zygote formation and warrants further investigation as a
      potential transmission blocking vaccine candidate.

PMID- 30297726
TI  - Baseline resistance-guided therapy does not enhance the response to interferon
      free treatment of HCV infection in real life.
AB  - Hepatitis C virus (HCV) response to direct-acting antivirals (DAAs) may be
      influenced by the presence of resistance-associated substitutions (RASs). This
      study aimed to assess if NS5A baseline RAS-guided treatment enhances the rate of
      sustained viral response (SVR) in naive HCV-infected patients in clinical
      practice. All HCV-infected patients who initiated treatment with interferon (IFN)
      free DAA-based regimens between March 2016 and May 2017 in 17 Spanish hospitals
      and who had evaluable SVR 12 weeks (SVR12) after the end of therapy were
      included. Patients had to be DAA naive, with the exception of sofosbuvir
      with/without IFN. In one hospital, participants received therapy guided by the
      presence of NS5A-RASs (RGT population). Patients enrolled in the remaining
      hospitals, without baseline RASs testing, constituted the control population. A
      total of 120 and 512 patients were included in the RGT and control populations,
      respectively. Nine (7.5%) individuals in the RGT population showed baseline NS5A
      RASs. All of them achieved SVR12. The SVR12 rate in the RGT population was 97.2%
      (three relapses) whereas it was 98.8% (six relapses) in the control population (p
      = 0.382). Our findings suggest that testing for baseline NS5A-RASs in naive HCV
      infected patients does not enhance the rate of SVR to DAA-based IFN-free therapy
      in clinical practice.

PMID- 30297728
TI  - Impact of the Coal Mining on the Spatial Distribution of Potentially Toxic Metals
      in Farmland Tillage Soil.
AB  - Coal mining areas are prone to hazardous element contamination because of mining
      activities and the resulting wastes, mainly including Cr, Ni, Cu, Zn, Cd and Pb.
      This study collected 103 samples of farmland tillage soil surrounding a coal mine
      in southwestern Shandong province and monitored the heavy metal concentrations of
      each sample by inductively coupled plasma mass spectrometer (ICP-MS). Statistics,
      geostatistics, and geographical information systems (GIS) were used to determine
      the spatial pattern of the potentially toxic metals above in the coal mining
      area. The results show that the toxic metal concentrations have wide ranges, but
      the average values for Cr, Ni, Cu, Zn, Cd and Pb are 72.16, 29.53, 23.07, 66.30,
      0.14 and 23.71 mg Kg-1, which mostly exceed the natural soil background contents
      of Shandong Province. The element pairs Ni-Cu, Ni-Zn, and Cu-Zn have relatively
      high correlation coefficients (0.805, 0.505, 0.613, respectively). The Kriging
      interpolation results show that the contents of soil toxic metals are influenced
      by coal mining activities. Moreover, micro-domain variation analysis revealed the
      toxic metals in the typical area of the coal transportation line. These findings
      offer systematic insight into the influence of coal mining activities on toxic
      metals in farmland tillage soil.

PMID- 30297727
TI  - Galanin neurons in the ventrolateral preoptic area promote sleep and heat loss in
      mice.
AB  - The preoptic area (POA) is necessary for sleep, but the fundamental POA circuits
      have remained elusive. Previous studies showed that galanin (GAL)- and GABA
      producing neurons in the ventrolateral preoptic nucleus (VLPO) express cFos after
      periods of increased sleep and innervate key wake-promoting regions. Although
      lesions in this region can produce insomnia, high frequency photostimulation of
      the POAGAL neurons was shown to paradoxically cause waking, not sleep. Here we
      report that photostimulation of VLPOGAL neurons in mice promotes sleep with low
      frequency stimulation (1-4 Hz), but causes conduction block and waking at
      frequencies above 8 Hz. Further, optogenetic inhibition reduces sleep.
      Chemogenetic activation of VLPOGAL neurons confirms the increase in sleep, and
      also reduces body temperature. In addition, chemogenetic activation of VLPOGAL
      neurons induces short-latency sleep in an animal model of insomnia. Collectively,
      these findings establish a causal role of VLPOGAL neurons in both sleep induction
      and heat loss.

PMID- 30297730
TI  - Preparation of NiAl2O4-Based Flexible Substrates for Metamaterials with Negative
      Dielectric Properties.
AB  - Various techniques are commonly used to produce nano-crystalline NiAl2O4
      materials; however, their practical applications in the microwave region remain
      very limited. In this work, flexible substrates for metamaterials containing two
      different concentrations of NiAl2O4 (labelled Ni36 and Ni42) have been
      synthesised using a sol-gel method. The formation of spinel structures in the
      synthesised materials is confirmed, and their crystalline sizes are determined
      using scanning electron microscopy, X-ray diffraction, and energy dispersive X
      ray techniques. The dielectric properties, conductivities, loss tangents, and
      other parameters of the NiAl2O4-based substrates are analysed to evaluate their
      applicability as dielectric materials for the microwave frequency range. The
      obtained results show that the fabricated Ni36 and Ni42 nickel aluminates possess
      dielectric constants of 4.94 and 4.97 and loss tangents of 0.01 and 0.007,
      respectively; in addition, they exhibit high flexibility and light weight, which
      make them suitable for applications as metamaterial substrates. The synthesised
      structures are also validated experimentally using a commercially available
      electromagnetic simulator; as a result, double negative behaviour of the flexible
      metamaterials has been observed. Furthermore, it is found that the prepared
      NiAl2O4 substrates can be used in the S-, C-, and X-bands of the microwave
      frequency region.

PMID- 30297729
TI  - Identification of novel acetylcholinesterase inhibitors designed by pharmacophore
      based virtual screening, molecular docking and bioassay.
AB  - In this study, pharmacophore based 3D QSAR models for human acetylcholinesterase
      (AChE) inhibitors were generated, with good significance, statistical values
      (r2training = 0.73) and predictability (q2training = 0.67). It was further
      validated by three methods (Fischer's test, decoy set and Guner-Henry scoring
      method) to show that the models can be used to predict the biological activities
      of compounds without costly and time-consuming synthesis. The criteria for
      virtual screening were also validated by testing the selective AChE inhibitors.
      Virtual screening experiments and subsequent in vitro evaluation of promising
      hits revealed a novel and selective AChE inhibitor. Thus, the findings reported
      herein may provide a new strategy for the discovery of selective AChE inhibitors.
      The IC50 value of compounds 5c and 6a presented selective inhibition of AChE
      without inhibiting butyrylcholinesterase (BChE) at uM level. Molecular docking
      studies were performed to explain the potent AChE inhibition of the target
      compounds studies to explain high affinity.

PMID- 30297732
TI  - Sulphide Re-Os geochronology links orogenesis, salt and Cu-Co ores in the Central
      African Copperbelt.
AB  - The origin of giant, sedimentary rock-hosted copper-cobalt (Cu-Co) provinces
      remains contentious, in part due to the lack of precise and reliable ages for
      mineralisation. As such, no consensus has been reached on the genetic model for
      ore formation, and the relationships between tectonism, palaeo-fluid circulation
      and mineralisation. Here, we link the timing of Cu-Co mineralisation in the
      Central African Copperbelt to compressional tectonics during the Lufilian Orogeny
      by using new ca. 609-473 Ma ages given by rhenium-osmium (Re-Os) isotope data for
      individual Cu-Co sulphides (carrolite and bornite) from the Cu-Co Kamoto deposit.
      The initial Os isotope composition of carrolite is compatible with the leaching
      of Os and Cu(-Co) from Mesoproterozoic Cu sulphide deposits hosted in fertile
      basement. In contrast, the ca. 473 Ma Cu-Au mineralisation stage, which is coeval
      with late- to post-compressional deformation, may be a distal expression of fluid
      flow and heat transfer caused by magmatic intrusions in the core of the
      collisional orogen. The Re-Os ages support a model for mineralisation driven by
      evaporite dissolution and percolation of large volumes of dense brines in the
      Katangan Basin during the Lufilian Orogeny.

PMID- 30297731
TI  - Incidence of notified Lyme borreliosis in Germany, 2013-2017.
AB  - Lyme borreliosis (LB) is the most commonly reported tick-borne disease in
      Germany. In 9/16 states, notification of erythema migrans (EM), acute
      neuroborreliosis (NB) and Lyme arthritis (LA) is mandatory. We describe incidence
      measures, time trends, geographical distribution and frequencies of
      manifestations to better understand LB epidemiology and target prevention
      measures. We used cases notified in the 9 states and confirmed by local health
      offices, 2013-2017, to calculate incidences by time, place and person.
      Altogether, we observed 56,446 cases. Disease onset peaked yearly in July.
      Incidence ranged from 26/100,000 (2015) to 41/100,000 (2013) with mean annual
      incidences 2013-2017 on district level between 0.5/100,000 and 138/100,000.
      Median age was 54 years with peaks in boys (5-9 years, mean incidence 36/100,000)
      and women (50-69 years, mean incidence 57/100,000). 95% experienced EM only, 2.7%
      NB and 2.1% LA. 54% were female, but more men had NB (56%) and LA (53%, p <
      0.001). Hospitalisation was recorded for 10% of LA and 71% of NB cases. LB
      remains an important public health concern in Germany with marked regional
      variation. To facilitate early diagnosis and treatment, health authorities should
      raise awareness among physicians and promote prevention strategies among the
      general population: tick-bite-protection, prompt tick removal and medical
      consultation.

PMID- 30297734
TI  - Hanbury-Brown and Twiss exchange and non-equilibrium-induced correlations in
      disordered, four-terminal graphene-ribbon conductor.
AB  - We have investigated current-current correlations in a cross-shaped conductor
      made of graphene. The mean free path of charge carriers is on the order of the
      ribbon width which leads to a hybrid conductor where there is diffusive transport
      in the device arms while the central connection region displays near ballistic
      transport. Our data on auto and cross correlations deviate from the predictions
      of Landauer-Buttiker theory, and agreement can be obtained only by taking into
      account contributions from non-thermal electron distributions at the inlets to
      the semiballistic center, in which the partition noise becomes strongly modified.
      The experimental results display distinct Hanbury - Brown and Twiss (HBT)
      exchange correlations, the strength of which is boosted by the non-equilibrium
      occupation-number fluctuations internal to this hybrid conductor. Our work
      demonstrates that variation in electron coherence along atomically-thin, two
      dimensional conductors has significant implications on their noise and cross
      correlation properties.

PMID- 30297733
TI  - Computational B-cell epitope identification and production of neutralizing murine
      antibodies against Atroxlysin-I.
AB  - Epitope identification is essential for developing effective antibodies that can
      detect and neutralize bioactive proteins. Computational prediction is a valuable
      and time-saving alternative for experimental identification. Current
      computational methods for epitope prediction are underused and undervalued due to
      their high false positive rate. In this work, we targeted common properties of
      linear B-cell epitopes identified in an individual protein class
      (metalloendopeptidases) and introduced an alternative method to reduce the false
      positive rate and increase accuracy, proposing to restrict predictive models to a
      single specific protein class. For this purpose, curated epitope sequences from
      metalloendopeptidases were transformed into frame-shifted Kmers (3 to 15 amino
      acid residues long). These Kmers were decomposed into a matrix of biochemical
      attributes and used to train a decision tree classifier. The resulting prediction
      model showed a lower false positive rate and greater area under the curve when
      compared to state-of-the-art methods. Our predictions were used for synthesizing
      peptides mimicking the predicted epitopes for immunization of mice. A predicted
      linear epitope that was previously undetected by an experimental immunoassay was
      able to induce neutralizing-antibody production in mice. Therefore, we present an
      improved prediction alternative and show that computationally identified epitopes
      can go undetected during experimental mapping.

PMID- 30297735
TI  - Attenuation of hypertension by C-fiber stimulation of the human median nerve and
      the concept-based novel device.
AB  - High blood pressure (BP) is a highly controllable risk factor for cardiovascular
      diseases; however, awareness of this condition and the rates of controlled
      hypertension are low. Experimental animal studies have shown that stimulation of
      the median nerve or PC6 acupoint over the wrist has effects on cardiovascular
      activities, including reductions in systolic and diastolic BPs. A proof-of
      concept study was conducted in humans to investigate whether stimulation of
      median nerve near PC6 acupoint decreased high BP, identify the optimal
      stimulation parameters for the BP-lowering effects of median nerve stimulation,
      and determine the specific peripheral nerves or types of afferent fibers
      mediating the BP-lowering effects. Median nerve stimulation was carried out
      bilaterally or unilaterally with different stimulation parameters, and the BP and
      heart rate were monitored. The afferent mechanisms underlying the effects of
      median nerve stimulation on hypertension were investigated via microneurography,
      A-fiber blocking experiments, and localized chemical or electrical stimulation.
      Bilateral median nerve stimulation at either low or high frequencies produced
      profound but transient reductions in systolic BP, which were elicited when median
      nerve stimulation was unilaterally applied at interelectrode distances of 2 and 4
      cm. Systolic BP was also reduced by electrical stimulation of the thumb on the
      palm side. Although microneurographic recordings revealed the excitation of both
      A- and C-fibers following median nerve stimulation, the median nerve-mediated
      reductions in BP were not affected by A-fiber blockade, and they were mimicked by
      the activation of C-fibers with capsaicin. The present results indicate that
      activation of C-fibers in the median nerve generates BP-lowering effects in
      humans. Based on our clinical study, an optimized median nerve stimulator was
      built and combined with a wrist BP monitor for simultaneous BP measurements and
      median nerve stimulation.

PMID- 30297737
TI  - The clinical code-breakers.

PMID- 30297738
TI  - Explore space using swarms of tiny satellites.

PMID- 30297736
TI  - Probing the origin of matching functional jaws: roles of Dlx5/6 in cranial neural
      crest cells.
AB  - Gnathostome jaws derive from the first pharyngeal arch (PA1), a complex structure
      constituted by Neural Crest Cells (NCCs), mesodermal, ectodermal and endodermal
      cells. Here, to determine the regionalized morphogenetic impact of Dlx5/6
      expression, we specifically target their inactivation or overexpression to NCCs.
      NCC-specific Dlx5/6 inactivation (NCC?Dlx5/6) generates severely hypomorphic
      lower jaws that present typical maxillary traits. Therefore, differently from
      Dlx5/6 null-embryos, the upper and the lower jaws of NCC?Dlx5/6 mice present a
      different size. Reciprocally, forced Dlx5 expression in maxillary NCCs provokes
      the appearance of distinct mandibular characters in the upper jaw. We conclude
      that: (1) Dlx5/6 activation in NCCs invariably determines lower jaw identity; (2)
      the morphogenetic processes that generate functional matching jaws depend on the
      harmonization of Dlx5/6 expression in NCCs and in distinct ectodermal
      territories. The co-evolution of synergistic opposing jaws requires the
      coordination of distinct regulatory pathways involving the same transcription
      factors in distant embryonic territories.

PMID- 30297739
TI  - ROS-induced R loops trigger a transcription-coupled but BRCA1/2-independent
      homologous recombination pathway through CSB.
AB  - Actively transcribed regions of the genome are protected by transcription-coupled
      DNA repair mechanisms, including transcription-coupled homologous recombination
      (TC-HR). Here we used reactive oxygen species (ROS) to induce and characterize TC
      HR at a transcribed locus in human cells. As canonical HR, TC-HR requires RAD51.
      However, the localization of RAD51 to damage sites during TC-HR does not require
      BRCA1 and BRCA2, but relies on RAD52 and Cockayne Syndrome Protein B (CSB).
      During TC-HR, RAD52 is recruited by CSB through an acidic domain. CSB in turn is
      recruited by R loops, which are strongly induced by ROS in transcribed regions.
      Notably, CSB displays a strong affinity for DNA:RNA hybrids in vitro, suggesting
      that it is a sensor of ROS-induced R loops. Thus, TC-HR is triggered by R loops,
      initiated by CSB, and carried out by the CSB-RAD52-RAD51 axis, establishing a
      BRCA1/2-independent alternative HR pathway protecting the transcribed genome.

PMID- 30297741
TI  - Collapse of genetic division of labour and evolution of autonomy in pellicle
      biofilms.
AB  - Closely related microorganisms often cooperate, but the prevalence and stability
      of cooperation between different genotypes remain debatable. Here, we track the
      evolution of pellicle biofilms formed through genetic division of labour and ask
      whether partially deficient partners can evolve autonomy. Pellicles of Bacillus
      subtilis rely on an extracellular matrix composed of exopolysaccharide (EPS) and
      the fibre protein TasA. In monocultures, ?eps and ?tasA mutants fail to form
      pellicles, but, facilitated by cooperation, they succeed in co-culture.
      Interestingly, cooperation collapses on an evolutionary timescale and ?tasA
      gradually outcompetes its partner ?eps. Pellicle formation can evolve
      independently from division of labour in ?eps and ?tasA monocultures, by
      selection acting on the residual matrix component, TasA or EPS, respectively.
      Using a set of interdisciplinary tools, we unravel that the TasA producer (?eps)
      evolves via an unconventional but reproducible substitution in TasA that
      modulates the biochemical properties of the protein. Conversely, the EPS producer
      (DeltatasA) undergoes genetically variable adaptations, all leading to enhanced
      EPS secretion and biofilms with different biomechanical properties. Finally, we
      revisit the collapse of division of labour between Deltaeps and DeltatasA in
      light of a strong frequency versus exploitability trade-off that manifested in
      the solitarily evolving partners. We propose that such trade-off differences may
      represent an additional barrier to evolution of division of labour between
      genetically distinct microorganisms.

PMID- 30297740
TI  - Primate immunodeficiency virus proteins Vpx and Vpr counteract transcriptional
      repression of proviruses by the HUSH complex.
AB  - Host factors that silence provirus transcription in CD4+ memory T cells help HIV
      1 escape eradication by the host immune system and by antiviral drugs1. These
      same factors, however, must be overcome for HIV-1 to propagate. Here we show that
      Vpx and Vpr encoded by diverse primate immunodeficiency viruses activate provirus
      transcription. Vpx and Vpr are adaptor proteins for the DCAF1-CUL4A/B E3
      ubiquitin ligase that degrade SAMHD1 and increase reverse transcription2-4.
      Nonetheless, Vpx and Vpr have effects on reporter gene expression that are not
      explained by SAMHD1 degradation5-8. A screen for factors that mimic these effects
      identified the human silencing hub (HUSH) complex, FAM208A (TASOR/RAP140),
      MPHOSPH8 (MPP8), PPHLN1 (PERIPHILIN) and MORC29-13. Vpx associated with the HUSH
      complex and decreased steady-state level of these proteins in a
      DCAF1/CUL4A/B/proteasome-dependent manner14,15. Replication kinetics of HIV-1 and
      SIVMAC was accelerated to a similar extent by vpx or FAM208A knockdown. Finally,
      vpx increased steady-state levels of LINE-1 ORF1p, as previously described for
      FAM208A disruption11. These results demonstrate that the HUSH complex represses
      primate immunodeficiency virus transcription, and that, to counteract this
      restriction, viral Vpx or Vpr proteins degrade the HUSH complex.

PMID- 30297742
TI  - Leveraging single-cell genomics to expand the fungal tree of life.
AB  - Environmental DNA surveys reveal that most fungal diversity represents uncultured
      species. We sequenced the genomes of eight uncultured species across the fungal
      tree of life using a new single-cell genomics pipeline. We show that, despite a
      large variation in genome and gene space recovery from each single amplified
      genome (SAG), >=90% can be recovered by combining multiple SAGs. SAGs provide
      robust placement for early-diverging lineages and infer a diploid ancestor of
      fungi. Early-diverging fungi share metabolic deficiencies and show unique gene
      expansions correlated with parasitism and unculturability. Single-cell genomics
      holds great promise in exploring fungal diversity, life cycles and metabolic
      potential.

PMID- 30297744
TI  - Coexistence theory and the frequency-dependence of priority effects.
AB  - Priority effects are commonly used to describe a broad suite of phenomena
      capturing the influence of species arrival order on the diversity, composition
      and function of ecological communities. Several studies have suggested reframing
      priority effects around the stabilizing and equalizing concepts of coexistence
      theory. We show that the only compatible priority effects are those characterized
      by positive frequency-dependence, irrespective of whether they emerge in
      equilibrium or non-equilibrium systems.

PMID- 30297743
TI  - Hyaluronic acid-CD44 interactions promote BMP4/7-dependent Id1/3 expression in
      melanoma cells.
AB  - BMP4/7-dependent expression of inhibitor of differentiation/DNA binding (Id)
      proteins 1 and 3 has been implicated in tumor progression and poor prognosis of
      malignant melanoma patients. Hyaluronic acid (HA), a pericellular matrix
      component, supports BMP7 signalling in murine chondrocytes through its receptor
      CD44. However, its role in regulating BMP signalling in melanoma is not clear. In
      this study we found that depletion of endogenously-produced HA by hyaluronidase
      treatment or by inhibition of HA synthesis by 4-methylumbelliferone (4-MU)
      resulted in reduced BMP4/7-dependent Id1/3 protein expression in mouse melanoma
      B16-F10 and Ret cells. Conversely, exogenous HA treatment increased BMP4/7
      dependent Id1/3 protein expression. Knockdown of CD44 reduced BMP4/7-dependent
      Id1/3 protein expression, and attenuated the ability of exogenous HA to stimulate
      Id1 and Id3 expression in response to BMP. Co-IP experiments demonstrated that
      CD44 can physically associate with the BMP type II receptor (BMPR) ACVR2B.
      Importantly, we found that coordinate expression of Id1 or Id3 with HA synthases
      HAS2, HAS3, and CD44 is associated with reduced overall survival of cutaneous
      melanoma patients. Our results suggest that HA-CD44 interactions with BMPR
      promote BMP4/7-dependent Id1/3 protein expression in melanoma, contributing to
      reduced survival in melanoma patients.

PMID- 30297746
TI  - Brian Maurer (1954-2018).

PMID- 30297745
TI  - Shark genomes provide insights into elasmobranch evolution and the origin of
      vertebrates.
AB  - Modern cartilaginous fishes are divided into elasmobranchs (sharks, rays and
      skates) and chimaeras, and the lack of established whole-genome sequences for the
      former has prevented our understanding of early vertebrate evolution and the
      unique phenotypes of elasmobranchs. Here we present de novo whole-genome
      assemblies of brownbanded bamboo shark and cloudy catshark and an improved
      assembly of the whale shark genome. These relatively large genomes (3.8-6.7 Gbp)
      contain sparse distributions of coding genes and regulatory elements and exhibit
      reduced molecular evolutionary rates. Our thorough genome annotation revealed Hox
      C genes previously hypothesized to have been lost, as well as distinct gene
      repertories of opsins and olfactory receptors that would be associated with
      adaptation to unique underwater niches. We also show the early establishment of
      the genetic machinery governing mammalian homoeostasis and reproduction at the
      jawed vertebrate ancestor. This study, supported by genomic, transcriptomic and
      epigenomic resources, provides a foundation for the comprehensive, molecular
      exploration of phenotypes unique to sharks and insights into the evolutionary
      origins of vertebrates.

PMID- 30297747
TI  - Adaptive transcription-splicing resynchronization upon losing an essential
      splicing factor.
AB  - Essential genes form the core of a genome and are therefore thought to be
      indispensable for cellular viability. However, recent findings have challenged
      this notion in that cells may survive in the absence of some essential genes
      provided that relevant genetic modifiers are in existence. We therefore
      hypothesized that the loss of an essential gene may not always be fatefully
      detrimental; instead, it may pave the way towards genome evolution. We
      experimentally tested this hypothesis in the context of pre-messenger RNA
      splicing by evolving yeast cells harbouring a permanent loss of the essential
      splicing factor Prp28 in the presence of a genetic modifier. Here, we show that
      cellular fitness can be restored by compensatory mutations that alter either the
      splicing machinery per se or the Spt-Ada-Gcn5 acetyltransferase transcription co
      activator complex in the cells with no Prp28. Biochemical and genetic analysis
      revealed that slowing down transcription compensates for splicing deficiency,
      which in turn boosts cellular fitness. In addition, we found that inefficient
      splicing also conversely decreases nascent RNA production. Taken together, our
      data suggest that transcription-splicing synchronization contributes to
      robustness in the gene-expression pathway and argue that the intrinsic
      interconnectivity within a biological system can be exploited for compensatory
      evolution and system re-optimization.

PMID- 30297748
TI  - Early neurogenomic response associated with variation in guppy female mate
      preference.
AB  - Understanding the evolution of mate choice requires dissecting the mechanisms of
      female preference, particularly how these differ among social contexts and
      preference phenotypes. Here, we studied the female neurogenomic response after
      only 10 min of mate exposure in both a sensory component (optic tectum) and a
      decision-making component (telencephalon) of the brain. By comparing the
      transcriptional response between females with and without preferences for
      colourful males, we identified unique neurogenomic elements associated with the
      female preference phenotype that are not present in females without preference. A
      network analysis revealed different properties for this response at the sensory
      processing and the decision-making levels, and we show that this response is
      highly centralized in the telencephalon. Furthermore, we identified an additional
      set of genes that vary in expression across social contexts, beyond mate
      evaluation. We show that transcription factors among these loci are predicted to
      regulate the transcriptional response of the genes we found to be associated with
      female preference.

PMID- 30297749
TI  - Functional shifts in microbial mats recapitulate early Earth metabolic
      transitions.
AB  - Phototrophic microbial mats dominated terrestrial ecosystems for billions of
      years, largely causing, through cyanobacterial oxygenic photosynthesis, but also
      undergoing, the Great Oxidation Event approximately 2.5 billion years ago. Taking
      a space-for-time approach based on the universality of core metabolic pathways
      expressed at ecosystem level, we studied gene content and co-occurrence networks
      in high-diversity metagenomes from spatially close microbial mats along a steep
      redox gradient. The observed functional shifts suggest that anoxygenic
      photosynthesis was present but not predominant under early Precambrian
      conditions, being accompanied by other autotrophic processes. Our data also
      suggest that, in contrast to general assumptions, anoxygenic photosynthesis
      largely expanded in parallel with the subsequent evolution of oxygenic
      photosynthesis and aerobic respiration. Finally, our observations might represent
      space-for-time evidence that the Wood-Ljungdahl carbon fixation pathway dominated
      phototrophic mats in early ecosystems, whereas the Calvin cycle probably evolved
      from pre-existing variants before becoming the dominant contemporary form of
      carbon fixation.

PMID- 30297751
TI  - Catalytic dehydrogenative decarboxyolefination of carboxylic acids.
AB  - Alkenes are among the most versatile building blocks and are widely used for the
      production of polymers, detergents and synthetic lubricants. Currently, alkenes
      are sourced from petroleum feedstocks such as naphtha. In light of the necessity
      to invent sustainable production methods, multiple approaches to making alkenes
      from abundant fatty acids have been evaluated. However, all attempts so far have
      required at least one stoichiometric additive, which is an obstruction for
      applications at larger scales. Here, we report an approach to making olefins from
      carboxylic acids, in which every additional reaction constituent can be used as a
      catalyst. We show how abundant fatty acids can be converted to alpha-olefins, and
      expand the method to include structurally complex carboxylic acids, giving access
      to synthetically versatile intermediates. Our approach is enabled by the
      cooperative interplay between a cobalt catalyst, which functions as a proton
      reduction catalyst, and a photoredox catalyst, which mediates oxidative
      decarboxylation; coupling both processes enables catalytic conversion of
      carboxylic acids to olefins.

PMID- 30297750
TI  - Inhibiting amyloid-beta cytotoxicity through its interaction with the cell
      surface receptor LilrB2 by structure-based design.
AB  - Inhibiting the interaction between amyloid-beta (Abeta) and a neuronal cell
      surface receptor, LilrB2, has been suggested as a potential route for treating
      Alzheimer's disease. Supporting this approach, Alzheimer's-like symptoms are
      reduced in mouse models following genetic depletion of the LilrB2 homologue. In
      its pathogenic, oligomeric state, Abeta binds to LilrB2, triggering a pathway to
      synaptic loss. Here we identify the LilrB2 binding moieties of Abeta (16KLVFFA21)
      and identify its binding site on LilrB2 from a crystal structure of LilrB2
      immunoglobulin domains D1D2 complexed to small molecules that mimic phenylalanine
      residues. In this structure, we observed two pockets that can accommodate the
      phenylalanine side chains of KLVFFA. These pockets were confirmed to be
      16KLVFFA21 binding sites by mutagenesis. Rosetta docking revealed a plausible
      geometry for the Abeta-LilrB2 complex and assisted with the structure-guided
      selection of small molecule inhibitors. These molecules inhibit Abeta-LilrB2
      interactions in vitro and on the cell surface and reduce Abeta cytotoxicity,
      which suggests these inhibitors are potential therapeutic leads against
      Alzheimer's disease.

PMID- 30297753
TI  - Cavitation energies can outperform dispersion interactions.
AB  - The accurate dissection of binding energies into their microscopic components is
      challenging, especially in solution. Here we study the binding of noble gases (He
      Xe) with the macrocyclic receptor cucurbit[5]uril in water by displacement of
      methane and ethane as 1H NMR probes. We dissect the hydration free energies of
      the noble gases into an attractive dispersive component and a repulsive one for
      formation of a cavity in water. This allows us to identify the contributions to
      host-guest binding and to conclude that the binding process is driven by
      differential cavitation energies rather than dispersion interactions. The free
      energy required to create a cavity to accept the noble gas inside the
      cucurbit[5]uril is much lower than that to create a similarly sized cavity in
      bulk water. The recovery of the latter cavitation energy drives the overall
      process, which has implications for the refinement of gas-storage materials and
      the understanding of biological receptors.

PMID- 30297752
TI  - Mining the cellular inventory of pyridoxal phosphate-dependent enzymes with
      functionalized cofactor mimics.
AB  - Pyridoxal phosphate (PLP) is an enzyme cofactor required for the chemical
      transformation of biological amines in many central cellular processes. PLP
      dependent enzymes (PLP-DEs) are ubiquitous and evolutionarily diverse, making
      their classification based on sequence homology challenging. Here we present a
      chemical proteomic method for reporting on PLP-DEs using functionalized cofactor
      probes. We synthesized pyridoxal analogues modified at the 2'-position, which are
      taken up by cells and metabolized in situ. These pyridoxal analogues are
      phosphorylated to functional cofactor surrogates by cellular pyridoxal kinases
      and bind to PLP-DEs via an aldimine bond which can be rendered irreversible by
      NaBH4 reduction. Conjugation to a reporter tag enables the subsequent
      identification of PLP-DEs using quantitative, label-free mass spectrometry. Using
      these probes we accessed a significant portion of the Staphylococcus aureus PLP
      DE proteome (73%) and annotate uncharacterized proteins as novel PLP-DEs. We also
      show that this approach can be used to study structural tolerance within PLP-DE
      active sites and to screen for off-targets of the PLP-DE inhibitor D-cycloserine.

PMID- 30297754
TI  - Quantum-state-controlled channel branching in cold Ne(3P2)+Ar chemi-ionization.
AB  - A prerequisite to gain a complete understanding of the most basic aspects of
      chemical reactions is the ability to perform experiments with complete control
      over the reactant degrees of freedom. By controlling these, details of a reaction
      mechanism can be investigated and ultimately manipulated. Here, we present a
      study of chemi-ionization-a fundamental energy-transfer reaction-under completely
      controlled conditions. The collision energy of the reagents was tuned from 0.02 K
      to 1,000 K, with the orientation of the excited Ne atom relative to Ar fully
      specified by an external magnetic field. Chemi-ionization of Ne(3P2) and Ar in
      these conditions enables a detailed investigation of how the reaction proceeds,
      and provides us with a means to control the branching ratio between the two
      possible reaction outcomes. The merged-beam experimental technique used here
      allows access to a low-energy regime in which the atoms dynamically reorient into
      a favourable configuration for reaction, irrespective of their initial
      orientations.

PMID- 30297755
TI  - Deletions linked to PROG1 gene participate in plant architecture domestication in
      Asian and African rice.
AB  - Improving the yield by modifying plant architecture was a key step during crop
      domestication. Here, we show that a 110-kb deletion on the short arm of
      chromosome 7 in Asian cultivated rice (Oryza sativa), which is closely linked to
      the previously identified PROSTRATE GROWTH 1 (PROG1) gene, harbors a tandem
      repeat of seven zinc-finger genes. Three of these genes regulate the plant
      architecture, suggesting that the deletion also promoted the critical transition
      from the prostrate growth and low yield of wild rice (O. rufipogon) to the erect
      growth and high yield of Asian cultivated rice. We refer to this locus as RICE
      PLANT ARCHITECTURE DOMESTICATION (RPAD). Further, a similar but independent 113
      kb deletion is detected at the RPAD locus in African cultivated rice. These
      results indicate that the deletions, eliminating a tandem repeat of zinc-finger
      genes, may have been involved in the parallel domestication of plant architecture
      in Asian and African rice.

PMID- 30297757
TI  - The 11th International Symposium on In Vivo Body Composition Studies.

PMID- 30297756
TI  - The mycoparasitic yeast Saccharomycopsis schoenii predates and kills multi-drug
      resistant Candida auris.
AB  - Candida auris has recently emerged as a multi-drug resistant fungal pathogen that
      poses a serious global health threat, especially for patients in hospital
      intensive care units (ICUs). C. auris can colonize human skin and can spread by
      physical contact or contaminated surfaces and equipment. Here, we show that the
      mycoparasitic yeast Saccharomycopsis schoenii efficiently kills both sensitive
      and multi-drug resistant isolates of C. auris belonging to the same clade, as
      well as clinical isolates of other pathogenic species of the Candida genus
      suggesting novel approaches for biocontrol.

PMID- 30297758
TI  - Low breastmilk vitamin A concentration is prevalent in rural Ethiopia.
AB  - BACKGROUND: There is scant information on the breastmilk vitamin A (BMVA)
      concentration of lactating women in developing countries, partly due to lack of
      methods applicable in-field. OBJECTIVE: To assess BMVA concentrations of samples
      collected from lactating women of children aged 6-23 months, in Mecha district,
      Ethiopia. SUBJECTS/METHODS: Data on socio-demographic and anthropometric
      characteristics were collected from randomly selected lactating women (n = 104).
      Breast milk samples were collected and vitamin A concentrations were analyzed
      using HPLC and iCheck FLUORO then the two measurements were compared. RESULTS:
      The prevalence of underweight (BMI < 18.5 kg/m2) among lactating women was 17%.
      Seventy six percent of the BMVA values were <1.05 umol/l and 81% were <8 ug/g
      fat. The mean BMVA concentration accounted to 41% of the estimated average value
      for mothers in developing countries. The BMVA values from HPLC and iCheck were
      correlated (r = 0.59, p = < 0.001), but it was not strong. CONCLUSIONS: The
      result indicates the low vitamin A status of the lactating women and their
      children. It further indicates that intake assessments should not use average
      BMVA composition. The possibility of using iCheck for monitoring interventions
      designed to improve vitamin A status of lactating women with low BMVA requires
      further investigation.

PMID- 30297759
TI  - Glycaemic and insulinaemic impact of oats soaked overnight in milk vs. cream of
      rice with and without sugar, nuts, and seeds: a randomized, controlled trial.
AB  - BACKGROUND/OBJECTIVES: Soaking oats overnight in milk renders them ready to eat
      the next morning, however, it is unknown whether oats prepared this way will
      retain its relatively low glycaemic and insulinaemic impact. Therefore, we
      compared the glycaemic, insulinaemic and subjective hunger responses elicited by
      oats soaked overnight in 110 g skim-milk (ONO) vs. cooked cream of rice cereal
      (CR), both with and without inclusions. SUBJECTS/METHODS: The project was
      performed at two research centers (Toronto, Winnipeg) as two separate studies
      each using a randomized, cross-over design with similar methods. The glycaemic
      and insulinaemic responses of overnight-fasted participants without diabetes
      (males:females: Toronto, 24:16; Winnipeg, 20:20) were measured for 3 h after
      consuming CR and ONO fed alone (Toronto) or with added sugar, nuts, and seeds
      (CRsns and ONOsns) (Winnipeg). Participants rated subjective hunger using visual
      analog scales. Data were analyzed by paired t-test. The primary endpoint was 0-2
      h incremental area under the curve (iAUC) for glucose. RESULTS: Mean glucose iAUC
      was 33% less, after ONO than CR (mean difference was 39 (51-27) mmol * min/l, p <
      0.0001) and 24% less, after ONOsns than CRsns (mean difference was 43 (65-21)
      mmol * min/l, p = 0.0003). Serum-insulin iAUC was 33% less, after ONO than CR
      (mean difference 57 (81-40) pmol * hl, p < 0.0001) and 32% less, after ONOsns
      than CRsns (966 (1360-572) pmol * h/l, p < 0.0001). In both Toronto and Winnipeg,
      subjective hunger ratings were similar across the two treatments. CONCLUSIONS:
      Oats prepared by soaking overnight in skimmed milk without and with inclusions
      retain their relatively low glycaemic and insulinaemic impact.

PMID- 30297760
TI  - Bioelectrical impedance analysis for body composition assessment: reflections on
      accuracy, clinical utility, and standardisation.
AB  - Bioelectrical impedance analysis is an extremely popular method for assessment of
      body composition. Despite its wide-spread use over the past thirty years, its
      accuracy and clinical value is still questioned. Most frequently, criticisms
      focus on its purported poor absolute accuracy and that different impedance
      analysers or prediction equations fail to measure body composition identically.
      This perspective review highlights that the magnitude of errors associated with
      impedance methods are not dissimilar to those observed for so-called gold
      standard methods. It is argued that the focus on statistically significant but
      small differences between methods can obscure operational equivalence and that
      such differences may be of minor clinical significance. Finally, the need for
      better standardization of protocols and the need for consensus on what is a
      minimal clinically important difference between methods is highlighted.

PMID- 30297761
TI  - Can legal restrictions of prenatal exposure to industrial trans-fatty acids
      reduce risk of childhood hematopoietic neoplasms? A population-based study.
AB  - BACKGROUND: Causes of most childhood hematopoietic neoplasms are unknown. Early
      age of occurrence suggests prenatal etiology. Positive associations have been
      reported between industrially produced trans-fatty acids (iTFAs) and risks of
      some cancers in adults. iTFAs are pro-inflammatory and adversely affect the
      beneficial effects of essential fatty acids, the latter is diminishing tumor
      growth. In 2004 Denmark legislated against the use of iTFA in foodstuffs. Using
      the entire population, we investigated if the changes in the legislation as a
      proxy to the reduced exposure to iTFA had affected the incidence of childhood
      hematopoietic neoplasms. METHODS: We used a Cox proportional hazard model to
      compare the hazard of childhood hematopoietic neoplasms among children born
      before and after the iTFA ban, as a proxy for fetal iTFA exposure. To take the
      potential secular trend in hematopoietic neoplasms into account, we modeled the
      variation in cancer risk across birth cohorts by a piecewise linear spline with a
      knot in 2004, which allowed a comparison of the hazard of childhood hematopoietic
      neoplasms between the time before and after the iTFA ban. RESULTS: Among children
      born in 1988-2008 in Denmark, 720 were diagnosed with hematopoietic neoplasms
      before the age of 7 years, corresponding to an overall incidence rate of 7.6 per
      100 000 person years. The incidence rates increased by 2% per cohort in 1988-2004
      (hazard ratio: 1.02 [1.01; 1.04]) and in 2004-2008 (hazard ratio: 1.02 [0.95;
      1.11]). CONCLUSIONS: No apparent benefit of the iTFA legislation in reducing
      childhood hematopoietic neoplasms was observed on population basis. Individual
      level data are needed to investigate any possible associations between biomarkers
      of iTFA intake and risk of childhood hematopoietic neoplasms.

PMID- 30297762
TI  - Fitness versus adiposity in cardiovascular disease risk.
AB  - Obesity and low cardiorespiratory fitness are both established predictors of
      cardiovascular disease morbidity and mortality. Whether the protective effects of
      fitness outweigh the deleterious effects of obesity, however, remains a topic of
      debate. To extend knowledge of the relative influence of fitness and fatness on
      cardiovascular disease outcomes, however, attention must be paid to measurement
      quality. Eliminating inherent bias of self-report and including the highest
      quality assessments of cardiorespiratory fitness and fatness simultaneously are
      imperative for head-to-head comparisons. Studies must move beyond body mass index
      and total body fat percentage to differentiate the heterogenous effects of
      various adipose tissue depots on cardiovascular risk. Imaging techniques that
      measure visceral adiposity and other risk-laden ectopic adipose depots while also
      quantifying cardioprotective adipose depots such as lower body subcutaneous fat
      and even non-adipose tissues such as skeletal muscle may further illuminate the
      influence of body composition on cardiovascular health. This review underscores
      key studies within a large body of literature that provide the foundation for the
      fit-vs.-fat debate in the context of cardiovascular disease risk, and identifies
      important considerations for future research.

PMID- 30297763
TI  - Coffee consumption in hemodialysis patients: how many?
AB  - BACKGROUND AND AIMS: Coffee is one of the most widely consumed beverages
      worldwide. However, fluid intake restriction is an important and difficult
      challenge for hemodialysis (HD) patients. The aim of this study was to analyze
      the effect of coffee intake on hydration and nutritional parameters of HD
      patients. METHODS: This was an observational, cross-sectional, multicenter study
      where 373 HD patients from 8 dialysis centers in Portugal were enrolled. A face
      to-face questionnaire was applied and patient's clinical and body composition
      parameters were analyzed. The sample was divided into 3 groups depending on
      coffee intake: group 1-don't drink coffee, group 2-drink 1-2 coffees/day and
      group 3-drink 3 or more coffees/day. Laboratory and body composition parameters
      were registered in the month prior to the questionnaire application. Body
      composition was assessed with the Body Composition Monitor (BCM; Fresenius
      Medical Care Deutschland GmbH, Germany). RESULTS: Patient's mean age was 67.2 +/-
      14.4 years and the mean HD vintage was 61.3 +/- 56.2 months. Patients who
      reported drinking 3 or more coffees daily were younger, presented higher levels
      of potassium, phosphorus, diastolic BP, albumin and interdialytic weight gain
      (IDWG) and lower dialysis adequacy (Kt/V). Regarding body composition, patients
      in the group 3 showed higher body cell mass index (BCMI) and lean tissue index
      (LTI). On the other hand, the group 1 were the oldest, had a higher Kt/V, a lower
      diastolic blood pressure (BP) and potassium levels, whereas G2 presented a lower
      LTI, BCMI and IDWG. CONCLUSIONS: Drinking 3 or more coffees daily increases the
      risk of a higher diastolic BP, potassium and IDWG in HD patients.

PMID- 30297764
TI  - Rapid and selective concentration of bacteria, viruses, and proteins using
      alternating current signal superimposition on two coplanar electrodes.
AB  - Dielectrophoresis (DEP) is usually effective close to the electrode surface.
      Several techniques have been developed to overcome its drawbacks and to enhance
      dielectrophoretic particle capture. Here we present a simple technique of
      superimposing alternating current DEP (high-frequency signals) and electroosmosis
      (EO; low-frequency signals) between two coplanar electrodes (gap: 25 MUm) using a
      lab-made voltage adder for rapid and selective concentration of bacteria,
      viruses, and proteins, where we controlled the voltages and frequencies of DEP
      and EO separately. This signal superimposition technique enhanced bacterial
      capture (Escherichia coli K-12 against 1-MUm-diameter polystyrene beads) more
      selectively (>99%) and rapidly (~30 s) at lower DEP (5 Vpp) and EO (1.2 Vpp)
      potentials than those used in the conventional DEP capture studies. Nanometer
      sized MS2 viruses and troponin I antibody proteins were also concentrated using
      the superimposed signals, and significantly more MS2 and cTnI-Ab were captured
      using the superimposed signals than the DEP (10 Vpp) or EO (2 Vpp) signals alone
      (p < 0.035) between the two coplanar electrodes and at a short exposure time (1
      min). This technique has several advantages, such as simplicity and low cost of
      electrode fabrication, rapid and large collection without electrolysis.

PMID- 30297765
TI  - Vav1 mutations identified in human cancers give rise to different oncogenic
      phenotypes.
AB  - Vav1 is physiologically active as a GDP/GTP nucleotide exchange factor (GEF) in
      the hematopoietic system. Overexpression of Vav1 in multiple tumor types is known
      to enhance oncogenicity, yet whether or not Vav1 is a bona fide oncogene is still
      a matter of debate. Although mutations in Vav1 were recently identified in human
      cancers of various origins, the functional activities of these mutants are not
      known. We tested the transforming potential of three mutations identified in
      human lung adenocarcinoma: E59K, D517E, and L801P. Results from several assays
      indicative of transforming activities such as rate of proliferation, growth in
      agar, and generation of tumors in NOD/SCID mice clearly indicated that E59K and
      D517E are highly transforming but L801P at the SH3 domain is not. The acquired
      oncogenic activity of these mutants can be attributed to their enhanced activity
      as GEFs for Rho/Rac GTPases. Deciphering of the mechanisms leading to
      overactivity of the tested mutants revealed that the E59K mutation facilitates
      cleavage of a truncated protein that is uncontrollably active as a GEF, while
      D517E generates a highly stable overexpressed protein that is also more active as
      a GEF than wild-type Vav1. These findings support the classification of Vav1 as a
      bona fide oncogene in human cancer.

PMID- 30297766
TI  - Fractionalized excitations in the partially magnetized spin liquid candidate
      YbMgGaO4.
AB  - Quantum spin liquids (QSLs) are exotic states of matter characterized by emergent
      gauge structures and fractionalized elementary excitations. The recently
      discovered triangular lattice antiferromagnet YbMgGaO4 is a promising QSL
      candidate, and the nature of its ground state is still under debate. Here we use
      neutron scattering to study the spin excitations in YbMgGaO4 under various
      magnetic fields. Our data reveal a dispersive spin excitation continuum with
      clear upper and lower excitation edges under a weak magnetic field (H = 2.5 T).
      Moreover, a spectral crossing emerges at the Gamma point at the Zeeman-split
      energy. The corresponding redistribution of the spectral weight and its field
      dependent evolution are consistent with the theoretical prediction based on the
      inter-band and intra-band spinon particle-hole excitations associated with the
      Zeeman-split spinon bands, implying the presence of fractionalized excitations
      and spinon Fermi surfaces in the partially magnetized QSL state in YbMgGaO4.

PMID- 30297768
TI  - Gene coexpression network analysis combined with metabonomics reveals the
      resistance responses to powdery mildew in Tibetan hulless barley.
AB  - Powdery mildew is a fungal disease that represents a ubiquitous threat to crop
      plants. Transcriptomic and metabolomic analyses were used to identify molecular
      and physiological changes in Tibetan hulless barley in response to powdery
      mildew. There were 3418 genes and 405 metabolites differentially expressed
      between the complete resistance cultivar G7 and the sensitive cultivar Z13.
      Weighted gene coexpression network analysis was carried out, and the
      differentially expressed genes were enriched in five and four major network
      modules in G7 and Z13, respectively. Further analyses showed that phytohormones,
      photosynthesis, phenylpropanoid biosynthesis, and flavonoid biosynthesis pathways
      were altered during Qingke-Blumeria graminis (DC.) f.sp. hordei (Bgh)
      interaction. Comparative analyses showed a correspondence between gene expression
      and metabolite profiles, and the activated defenses resulted in changes of
      metabolites involved in plant defense response, such as phytohormones, lipids,
      flavone and flavonoids, phenolamides, and phenylpropanoids. This study enabled
      the identification of Bgh responsive genes and provided new insights into the
      dynamic physiological changes that occur in Qingke during response to powdery
      mildew. These findings greatly improve our understanding of the mechanisms of
      induced defense response in Qingke and will provide new clues for the development
      of resistant Tibetan hulless barley varieties.

PMID- 30297767
TI  - Dopamine-endocannabinoid interactions mediate spike-timing-dependent potentiation
      in the striatum.
AB  - Dopamine modulates striatal synaptic plasticity, a key substrate for action
      selection and procedural learning. Thus, characterizing the repertoire of
      activity-dependent plasticity in striatum and its dependence on dopamine is of
      crucial importance. We recently unraveled a striatal spike-timing-dependent long
      term potentiation (tLTP) mediated by endocannabinoids (eCBs) and induced with few
      spikes (~5-15). Whether this eCB-tLTP interacts with the dopaminergic system
      remains to be investigated. Here, we report that eCB-tLTP is impaired in a rodent
      model of Parkinson's disease and rescued by L-DOPA. Dopamine controls eCB-tLTP
      via dopamine type-2 receptors (D2R) located presynaptically in cortical
      terminals. Dopamine-endocannabinoid interactions via D2R are required for the
      emergence of tLTP in response to few coincident pre- and post-synaptic spikes and
      control eCB-plasticity by modulating the long-term potentiation (LTP)/depression
      (LTD) thresholds. While usually considered as a depressing synaptic function, our
      results show that eCBs in the presence of dopamine constitute a versatile system
      underlying bidirectional plasticity implicated in basal ganglia pathophysiology.

PMID- 30297770
TI  - Serially measured pre-diagnostic levels of serum cytokines and risk of brain
      cancer in active component military personnel.
AB  - BACKGROUND: There is growing evidence that history of allergic or autoimmune
      disease is associated with reduced risk of glioma, but few prospective studies
      have explored the biological basis. To assess associations with immune conditions
      and levels of 14 cytokines in serial prediagnostic serum samples, we conducted a
      study of glioma/brain cancer nested in a cohort of active component military
      personnel. METHODS: A total of 457 case-control sets were ascertained from the
      Department of Defense (DoD) Automated Central Tumour Registry, Defense Medical
      Surveillance System (DMSS) database, and DoD Serum Repository. These were
      individually matched on sex, race/ethnicity, birth year, number of serum samples
      (1, 2 or 3), and date(s) of sample collection. We obtained diagnoses of pre
      existing immune-related conditions from the DMSS database and measured cytokines
      using Meso Scale Discovery assays. Statistical analyses included conditional
      logistic regression. RESULTS: Overall association between glioma and prior immune
      related conditions was null. Higher levels of IL-15 and IL-16 were independently
      associated with lower glioma risks (Ptrend = 0.002 and Ptrend = 0.001); both
      associations were more pronounced in individuals with prior immune conditions
      (Pheterogeneity = 0.0009 and Pheterogeneity = 0.031). CONCLUSIONS: Associations
      with pre-diagnostic levels of IL-15 and IL-16 and their modification by diagnosis
      of immune-related conditions support the importance of immune alterations in
      glioma aetiology years before diagnosis.

PMID- 30297769
TI  - Pressure tuning of charge ordering in iron oxide.
AB  - A Verwey-type charge-ordering transition in magnetite at 120 K leads to the
      formation of linear units of three iron ions with one shared electron, called
      trimerons. The recently-discovered iron pentoxide (Fe4O5) comprising mixed-valent
      iron cations at octahedral chains, demonstrates another unusual charge-ordering
      transition at 150 K involving competing formation of iron trimerons and dimerons.
      Here, we experimentally show that applied pressure can tune the charge-ordering
      pattern in Fe4O5 and strongly affect the ordering temperature. We report two
      charge-ordered phases, the first of which may comprise both dimeron and trimeron
      units, whereas, the second exhibits an overall dimerization involving both the
      octahedral and trigonal-prismatic chains of iron in the crystal structure. We
      link the dramatic change in the charge-ordering pattern in the second phase to
      redistribution of electrons between the octahedral and prismatic iron chains, and
      propose that the average oxidation state of the iron cations can pre-determine a
      charge-ordering pattern.

PMID- 30297771
TI  - Reply to comment of "ERK and p38MAPK combine to improve survival in patients with
      BRAF mutant colorectal cancer".

PMID- 30297772
TI  - Comment on "ERK and p38MAPK combine to improve survival in patients with BRAF
      mutant colorectal cancer".

PMID- 30297773
TI  - Risk of diabetes after para-aortic radiation for testicular cancer.
AB  - BACKGROUND: While the risk of diabetes is increased following radiation exposure
      to the pancreas among childhood cancer survivors, its association among
      testicular cancer (TC) survivors has not been investigated. METHODS: Diabetes
      risk was studied in 2998 1-year TC survivors treated before 50 years of age with
      orchidectomy with/without radiotherapy between 1976 and 2007. Diabetes incidence
      was compared with general population rates. Treatment-specific risk of diabetes
      was assessed using a case-cohort design. RESULTS: With a median follow-up of 13.4
      years, 161 TC survivors were diagnosed with diabetes. Diabetes risk was not
      increased compared to general population rates (standardised incidence ratios
      (SIR): 0.9; 95% confidence interval (95% CI): 0.7-1.1). Adjusted for age, para
      aortic radiotherapy was associated with a 1.66-fold (95% CI: 1.05-2.62) increased
      diabetes risk compared to no radiotherapy. The excess hazard increased with 0.31
      with every 10 Gy increase in the prescribed radiation dose (95% CI: 0.11-0.51, P
      = 0.003, adjusted for age and BMI); restricted to irradiated patients the excess
      hazard increased with 0.33 (95% CI: -0.14 to 0.81, P = 0.169) with every 10 Gy
      increase in radiation dose. CONCLUSION: Compared to surgery only, para-aortic
      irradiation is associated with increased diabetes risk among TC survivors.

PMID- 30297774
TI  - Reconfigurable photoactuator through synergistic use of photochemical and
      photothermal effects.
AB  - A reconfigurable actuator is a stimuli-responsive structure that can be
      programmed to adapt different shapes under identical stimulus. Reconfigurable
      actuators that function without control circuitry and are fueled remotely are in
      great demand to devise adaptive soft robotic devices. Yet, obtaining fast and
      reliable reconfiguration remains a grand challenge. Here we report a facile
      fabrication pathway towards reconfigurability, through synergistic use of
      photochemical and photothermal responses in light-active liquid crystal polymer
      networks. We utilize azobenzene photoisomerization to locally control the cis
      isomer content and to program the actuator response, while subsequent
      photothermal stimulus actuates the structure, leading to shape morphing. We
      demonstrate six different shapes reconfigured from one single actuator under
      identical illumination conditions, and a light-fueled smart gripper that can be
      commanded to either grip and release or grip and hold an object after ceasing the
      illumination. We anticipate this work to enable all-optical control over actuator
      performance, paving way towards reprogrammable soft micro-robotics.

PMID- 30297775
TI  - Salt concentration and charging velocity determine ion charge storage mechanism
      in nanoporous supercapacitors.
AB  - A fundamental understanding of ion charge storage in nanoporous electrodes is
      essential to improve the performance of supercapacitors or devices for capacitive
      desalination. Here, we employ in situ X-ray transmission measurements on
      activated carbon supercapacitors to study ion concentration changes during
      electrochemical operation. Whereas counter-ion adsorption was found to dominate
      at small electrolyte salt concentrations and slow cycling speed, ion replacement
      prevails for high molar concentrations and/or fast cycling. Chronoamperometry
      measurements reveal two distinct time regimes of ion concentration changes. In
      the first regime the supercapacitor is charged, and counter- and co-ion
      concentration changes align with ion replacement and partially co-ion expulsion.
      In the second regime, the electrode charge remains constant, but the total ion
      concentration increases. We conclude that the initial fast charge neutralization
      in nanoporous supercapacitor electrodes leads to a non-equilibrium ion
      configuration. The subsequent, charge-neutral equilibration slowly increases the
      total ion concentration towards counter-ion adsorption.

PMID- 30297776
TI  - Author Correction: Accuracy and Precision of Tidal Wetland Soil Carbon Mapping in
      the Conterminous United States.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30297777
TI  - Quasiparticle interference and nonsymmorphic effect on a floating band surface
      state of ZrSiSe.
AB  - Non-symmorphic crystals are generating great interest as they are commonly found
      in quantum materials, like iron-based superconductors, heavy-fermion compounds,
      and topological semimetals. A new type of surface state, a floating band, was
      recently discovered in the nodal-line semimetal ZrSiSe, but also exists in many
      non-symmorphic crystals. Little is known about its physical properties. Here, we
      employ scanning tunneling microscopy to measure the quasiparticle interference of
      the floating band state on ZrSiSe (001) surface and discover rotational symmetry
      breaking interference, healing effect and half-missing-type anomalous Umklapp
      scattering. Using simulation and theoretical analysis we establish that the
      phenomena are characteristic properties of a floating band surface state.
      Moreover, we uncover that the half-missing Umklapp process is derived from the
      glide mirror symmetry, thus identify a non-symmorphic effect on quasiparticle
      interferences. Our results may pave a way towards potential new applications of
      nanoelectronics.

PMID- 30297779
TI  - Misreading chaperone-substrate complexes from random noise.

PMID- 30297780
TI  - Reply to 'Misreading chaperone-substrate complexes from random noise'.

PMID- 30297778
TI  - A novel class of microRNA-recognition elements that function only within open
      reading frames.
AB  - MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in
      mRNAs, thereby silencing gene expression at the post-transcriptional level.
      Multiple reports have also indicated the ability of miRNAs to target protein
      coding sequences (CDS); however, miRNAs have been generally believed to function
      through similar mechanisms regardless of the locations of their sites of action.
      Here, we report a class of miRNA-recognition elements (MREs) that function
      exclusively in CDS regions. Through functional and mechanistic characterization
      of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require
      extensive base-pairing at the 3' side rather than the 5' seed; cause gene
      silencing in an Argonaute-dependent but GW182-independent manner; and repress
      translation by inducing transient ribosome stalling instead of mRNA
      destabilization. These findings reveal distinct mechanisms and functional
      consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS
      targeted miRNAs may use a translational quality-control-related mechanism to
      regulate translation in mammalian cells.

PMID- 30297782
TI  - Multiple uncertainties require a change of conservation practices for saproxylic
      beetles in managed temperate forests.
AB  - In Europe, intensive forest management has severely compromised the habitat of
      forest insects, especially saproxylic beetles, due to the removal of deadwood and
      veteran trees. The loss of insect diversity may disrupt ecosystem functioning and
      affect the provision of important ecosystem goods and services in the future.
      Here we propose a novel approach for the implementation of conservation policies,
      by optimally allocating forest reserves and deadwood islands under multiple
      sources of uncertainty and minimizing economic risk. We use the saproxylic beetle
      Lucanus cervus as umbrella species, requiring that deadwood islands were spaced
      within its dispersal capacity. We show that current management and conservation
      practices are increasingly inefficient under changing environmental conditions
      and that the consideration of uncertainty requires a major expansion of
      conservation areas. Moreover, our results indicate that a strong diversification
      of management regimes, with a focus on selection forest systems, is required to
      reduce economic risk of forest management. We conclude that the integration of
      uncertainty into conservation planning may reduce the trade-off between
      production and conservation objectives in forest landscapes and is key to
      increase the efficiency of forest management in the future.

PMID- 30297781
TI  - Blood meal-induced inhibition of vector-borne disease by transgenic microbiota.
AB  - Vector-borne diseases are a substantial portion of the global disease burden; one
      of the deadliest of these is malaria. Vector control strategies have been
      hindered by mosquito and pathogen resistances, and population alteration
      approaches using transgenic mosquitos still have many hurdles to overcome before
      they can be implemented in the field. Here we report a paratransgenic control
      strategy in which the microbiota of Anopheles stephensi was engineered to produce
      an antiplasmodial effector causing the mosquito to become refractory to
      Plasmodium berghei. The midgut symbiont Asaia was used to conditionally express
      the antiplasmodial protein scorpine only when a blood meal was present. These
      blood meal inducible Asaia strains significantly inhibit pathogen infection, and
      display improved fitness compared to strains that constitutively express the
      antiplasmodial effector. This strategy may allow the antiplasmodial bacterial
      strains to survive and be transmitted through mosquito populations, creating an
      easily implemented and enduring vector control strategy.

PMID- 30297783
TI  - Personalized Integrated Network Modeling of the Cancer Proteome Atlas.
AB  - Personalized (patient-specific) approaches have recently emerged with a precision
      medicine paradigm that acknowledges the fact that molecular pathway structures
      and activity might be considerably different within and across tumors. The
      functional cancer genome and proteome provide rich sources of information to
      identify patient-specific variations in signaling pathways and activities within
      and across tumors; however, current analytic methods lack the ability to exploit
      the diverse and multi-layered architecture of these complex biological networks.
      We assessed pan-cancer pathway activities for >7700 patients across 32 tumor
      types from The Cancer Proteome Atlas by developing a personalized cancer-specific
      integrated network estimation (PRECISE) model. PRECISE is a general Bayesian
      framework for integrating existing interaction databases, data-driven de novo
      causal structures, and upstream molecular profiling data to estimate cancer
      specific integrated networks, infer patient-specific networks and elicit
      interpretable pathway-level signatures. PRECISE-based pathway signatures, can
      delineate pan-cancer commonalities and differences in proteomic network biology
      within and across tumors, demonstrates robust tumor stratification that is both
      biologically and clinically informative and superior prognostic power compared to
      existing approaches. Towards establishing the translational relevance of the
      functional proteome in research and clinical settings, we provide an online,
      publicly available, comprehensive database and visualization repository of our
      findings ( https://mjha.shinyapps.io/PRECISE/ ).

PMID- 30297784
TI  - Mammographic Density Distribution of Healthy Taiwanese Women and its Naturally
      Decreasing Trend with Age.
AB  - We analysed typical mammographic density (MD) distributions of healthy Taiwanese
      women to augment existing knowledge, clarify cancer risks, and focus public
      health efforts. From January 2011 to December 2015, 88,193 digital mammograms
      were obtained from 69,330 healthy Taiwanese women (average, 1.27 mammograms
      each). MD measurements included dense volume (DV) and volumetric density
      percentage (VPD) and were quantified by fully automated volumetric density
      estimation and Box-Cox normalization. Prediction of the declining MD trend was
      estimated using curve fitting and a rational model. Normalized DV and VPD Lowess
      curves demonstrated similar but non-identical distributions. In high-density
      grade participants, the VPD increased from 12.45% in the 35-39-year group to
      13.29% in the 65-69-year group but only from 5.21% to 8.47% in low-density
      participants. Regarding the decreased cumulative VPD percentage, the mean MD
      declined from 12.79% to 19.31% in the 45-50-year group versus the 50-55-year
      group. The large MD decrease in the fifth decade in this present study was
      similar to previous observations of Western women. Obtaining an MD distribution
      model with age improves the understanding of breast density trends and age
      variations and provides a reference for future studies on associations between MD
      and cancer risk.

PMID- 30297785
TI  - Angle-dependent electron-electron correlation in the single ionization of H2 in
      strong laser fields.
AB  - The one-photon ionization and tunneling ionization of H2 exposed to strong XUV
      and infrared laser pulses are studied by numerically simulating the four
      dimensional time-dependent Schrodinger equation, which includes two-electron
      dynamics for arbitrary angle between the molecular axis and the laser
      polarization direction. In the one-photon single ionization of H2, one electron
      escapes fast and the other bound electron is not disturbed but remains in
      coherent superposition of two electronic states of [Formula: see text]. In
      another case, under the irradiation of strong infrared laser pulses, one electron
      tunnels through the laser-dressed Coulomb barrier, and the other bound electron
      has enough time to adapt to the potential of [Formula: see text] and thus is
      prone to transfer to the ground electronic state of [Formula: see text]. In the
      intermediate regime, between the one photon and tunneling regimes, this electron
      electron correlation depends strongly on the laser frequency, laser intensity and
      on the angle between laser polarization and the molecular axis.

PMID- 30297787
TI  - Transcriptomic analysis reveals a controlling mechanism for NLRP3 and IL-17A in
      dextran sulfate sodium (DSS)-induced colitis.
AB  - The incidence of inflammatory bowel disease (IBD) has markedly increased. Our
      research findings during the past showed that medicinal plant extracts and the
      derived phytochemical components from Wedelia chinensis (WC) can have strong anti
      colitis activities. Here, we further identified the key component phytochemicals
      from active fractions of different WC preparations (WCHA) that are responsible
      for the protective effect of WCHA in colitis mice. Of the 3 major compounds
      (wedelolactone, luteolin and apigenin) in this fraction, luteolin had the highest
      anti-inflammatory effect in vivo. Using a next-generation sequencing (NGS) (e.g.,
      RNA-seq) system to analyze the transcriptome of colorectal cells/tissues in mice
      with dextran sulfate sodium (DSS)-induced colitis with/without phytochemicals
      treatment, luteolin was found to strongly suppress the DSS-activated IL-17
      pathway in colon tissue. In addition, co-treatment with wedelolactone and
      luteolin had a synergistic effect on the expression level of some IL-17 pathway
      related genes. Interestingly, our NGS analyses also indicated that luteolin and
      wedelolactone can specifically suppress the expression of NLRP3 and NLRP1. Using
      a 3-dimensional cell co-culture system, we further demonstrated that luteolin
      could efficiently suppress NLRP3 expression via disruption of IL-17A signaling in
      inflamed colon tissue, which also indicates the pharmacological potential of
      luteolin and wedelolactone in treating IBD.

PMID- 30297788
TI  - Somatic alterations in circulating cell-free DNA of oesophageal carcinoma
      patients during primary staging are indicative for post-surgical tumour
      recurrence.
AB  - Oesophageal cancer (OC) has high mortality. This study aims at determining the
      feasibility of liquid biopsies for genomic profiling in early stage OC, comparing
      two different technologies for mutational analysis in circulating cell -free DNA
      (ccfDNA) and evaluating the clinical impact of these somatic alterations during
      primary staging. In 25 patients with locally advanced OC, endoscopic tumour
      biopsies and simultaneous blood samples were taken during primary staging.
      Genomic DNA from biopsies and ccfDNA were analysed for mutations using a 12 gene
      panel next-generation sequencing (NGS) assay as well as digital droplet PCR
      (ddPCR). Genetic data was correlated with patients' outcome. In 21 of the tested
      biopsies (84%) at least one somatic mutation was detected by NGS. Mutations
      detected by NGS were detectable by ddPCR with similar allele frequencies. In
      three out of the 21 patients with proven mutations, the same mutations were also
      detectable in ccfDNA using NGS (14%). In contrast, ddPCR detected mutations in
      ccfDNA of five additional patients (8/21, 38%). Post-surgical outcome analysis
      was performed for those patients who had received complete tumour resection (n =
      16). Five of them suffered from an early relapse within the first year after
      surgery, including four with detectable somatic mutations in ccfDNA during
      primary staging. Taken together, we showed a higher sensitivity for ddPCR
      compared to NGS in detecting mutated ccfDNA in OC. Detection of somatically
      altered ccfDNA during primary staging seems to be indicative for post-surgical
      tumour recurrence.

PMID- 30297786
TI  - Electrophysiological evidence for abnormal glutamate-GABA association following
      psychosis onset.
AB  - Previous studies have shown glutamatergic dysfunction and gamma-aminobutyric acid
      (GABA)-ergic dysfunction in schizophrenia. Animal studies suggest that N-methyl-D
      aspartate receptor (NMDAR) dysfunction and GABA-ergic dysfunction interact with
      each other and lead to alterations in excitatory/inhibitory balance. The NMDAR
      and GABAergic-interneuron functions may be indexed by mismatch negativity (MMN)
      and auditory steady-state gamma-band response (ASSR), respectively. However, no
      previous studies have tested the hypothesis of an abnormal association between
      MMN and gamma-band ASSR in the same patients to identify the in vivo evidence of
      NMDAR-GABA association during the early stages of psychosis. Participants were
      individuals with recent-onset schizophrenia (ROSZ; N = 21), ultra-high risk (UHR;
      N = 27), and healthy controls (HCs; N = 24). The MMN amplitude was significantly
      impaired in ROSZ (p = 0.001, d = 1.20) and UHR (p = 0.003, d = 1.01) compared
      with HCs. The intertrial phase coherence (ITC) index of gamma-band ASSR was
      significantly reduced in ROSZ compared with HCs (p < 0.001, d = -1.27) and UHR (p
      = 0.032, d = -0.75). The event-related spectral perturbation (ERSP) index of
      gamma-band ASSR was significantly smaller in ROSZ compared with HCs (p < 0.001, d
      = -1.21). The MMN amplitude was significantly correlated with the ITC in ROSZ (r
      = -0.69, p < 0.001). These findings provide the first in vivo evidence that an
      abnormal association of the electrophysiological indices of NMDAR and GABA
      dysfunctions may be present in recent-onset schizophrenia.

PMID- 30297789
TI  - Typing tumors using pathways selected by somatic evolution.
AB  - Many recent efforts to analyze cancer genomes involve aggregation of mutations
      within reference maps of molecular pathways and protein networks. Here, we find
      these pathway studies are impeded by molecular interactions that are functionally
      irrelevant to cancer or the patient's tumor type, as these interactions diminish
      the contrast of driver pathways relative to individual frequently mutated genes.
      This problem can be addressed by creating stringent tumor-specific networks of
      biophysical protein interactions, identified by signatures of epistatic selection
      during tumor evolution. Using such an evolutionarily selected pathway (ESP) map,
      we analyze the major cancer genome atlases to derive a hierarchical
      classification of tumor subtypes linked to characteristic mutated pathways. These
      pathways are clinically prognostic and predictive, including the TP53-AXIN
      ARHGEF17 combination in liver and CYLC2-STK11-STK11IP in lung cancer, which we
      validate in independent cohorts. This ESP framework substantially improves the
      definition of cancer pathways and subtypes from tumor genome data.

PMID- 30297790
TI  - Regenerative potential of induced pluripotent stem cells derived from patients
      undergoing haemodialysis in kidney regeneration.
AB  - Kidney regeneration from pluripotent stem cells is receiving a lot of attention
      because limited treatments are currently available for chronic kidney disease
      (CKD). It has been shown that uremic state in CKD is toxic to somatic
      stem/progenitor cells, such as endothelial progenitor and mesenchymal stem cells,
      affecting their differentiation and angiogenic potential. Recent studies reported
      that specific abnormalities caused by the non-inherited disease are often
      retained in induced pluripotent stem cell (iPSC)-derived products obtained from
      patients. Thus, it is indispensable to first assess whether iPSCs derived from
      patients with CKD due to non-inherited disease (CKD-iPSCs) have the ability to
      generate kidneys. In this study, we generated iPSCs from patients undergoing
      haemodialysis due to diabetes nephropathy and glomerulonephritis (HD-iPSCs) as
      representatives of CKD-iPSCs or from healthy controls (HC-iPSCs). HD-iPSCs
      differentiated into nephron progenitor cells (NPCs) with similar efficiency to HC
      iPSCs. Additionally, HD-iPSC-derived NPCs expressed comparable levels of NPC
      markers and differentiated into vascularised glomeruli upon transplantation into
      mice, as HC-iPSC-derived NPCs. Our results indicate the potential of HD-iPSCs as
      a feasible cell source for kidney regeneration. This is the first study paving
      the way for CKD patient-stem cell-derived kidney regeneration, emphasising the
      potential of CKD-iPSCs.

PMID- 30297791
TI  - A reference document on Permissible Limits for solvents and buffers during in
      vitro antimalarial screening.
AB  - Antimalarial drug discovery expands on targeted and phenotype-based screening of
      potential inhibitory molecules to ascertain overall efficacy, phenotypic
      characteristics and toxicity, prior to exploring pharmacological optimizations.
      Candidate inhibitors may have varying chemical properties, thereby requiring
      specific reconstitution conditions to ensure solubility, stability or
      bioavailability. Hence, a variety of solvents, buffers, detergents and
      stabilizers become part of antimalarial efficacy assays, all of which, above
      certain threshold could interfere with parasite viability, invasion or red blood
      cell properties leading to misinterpretation of the results. Despite their
      routine use across malaria research laboratories, there is no documentation on
      non-toxic range for common constituents including DMSO, glycerol, ethanol and
      methanol. We herein constructed a compatibility reference guide for 14 such
      chemicals and estimated their Permissible Limit against P. falciparum asexual
      stages at which viability and replication of parasites are not compromised. We
      also demonstrate that at the estimated Permissible Limit, red blood cells remain
      healthy and viable for infection by merozoites. Taken together, this dataset
      provides a valuable reference tool for the acceptable concentration range for
      common chemicals during in vitro antimalarial tests.

PMID- 30297792
TI  - Cortical visual processing evokes short-latency reward-predicting cue responses
      in primate midbrain dopamine neurons.
AB  - After classical conditioning dopamine (DA) neurons exhibit short latency
      responses to reward-predicting visual cues. At least two possible projections
      could induce such DA responses; the cortical and subcortical visual pathways. Our
      recent study has shown that after a lesion of the striate cortex (V1), the
      superior colliculus (SC), a critical node of the subcortical visual pathway, can
      mediate short latency cue responses in the DA neurons of macaque monkeys. An
      obvious question then is does the cortical pathway have a similar capacity? Using
      the monkeys with a unilateral V1 lesion that took part in the preceding study, we
      recorded DA activity while they were performing the same classical conditioning
      task. However, in this study conditioned visual stimuli were presented to the
      intact visual field, and the effects of ipsilateral SC inactivation were
      examined. We found that after the SC was inactivated by injections of muscimol
      both conditioned behavioral responding and reward-predicting, short latency (~100
      ms) cue-elicited DA neuronal responses were unaffected These results indicate
      that the intact cortical visual pathway can also mediate short latency cue
      elicited responses in DA neurons in the absence of a normally functioning
      subcortical visual system.

PMID- 30297794
TI  - Application of spin-crossover water soluble nanoparticles for use as MRI contrast
      agents.
AB  - Water soluble spin-crossover (SCO) iron(II) nanoparticles (NPs) were synthesized
      by the polyethylene glycol (PEG) coating of [Fe(Htrz)3-3*(NH2trz)3*](BF4)2 (x =
      0, 0.1, 0.5 and 1). The NPs with x = 0.1 show gradual SCO behavior over 280-330 K
      in water. The relaxation times, T1 and T2, were determined and the thermally
      responsive T2 values making these NPs a candidate for use as a MRI contrast
      agent.

PMID- 30297793
TI  - Porphyromonas gingivalis bypasses epithelial barrier and modulates fibroblastic
      inflammatory response in an in vitro 3D spheroid model.
AB  - Porphyromonas gingivalis-induced inflammatory effects are mostly investigated in
      monolayer cultured cells. The aim of this study was to develop a 3D spheroid
      model of gingiva to take into account epithelio-fibroblastic interactions. Human
      gingival epithelial cells (ECs) and human oral fibroblasts (FBs) were cultured by
      hanging drop method to generate 3D microtissue (MT) whose structure was analyzed
      on histological sections and the cell-to-cell interactions were observed by
      scanning and transmission electron microscopy (SEM and TEM). MTs were infected by
      P. gingivalis and the impact on cell death (Apaf-1, caspase-3), inflammatory
      markers (TNF-alpha, IL-6, IL-8) and extracellular matrix components (Col-IV, E
      cadherin, integrin beta1) was evaluated by immunohistochemistry and RT-qPCR.
      Results were compared to those observed in situ in experimental periodontitis and
      in human gingival biopsies. MTs exhibited a well-defined spatial organization
      where ECs were organized in an external cellular multilayer, while, FBs
      constituted the core. The infection of MT demonstrated the ability of P.
      gingivalis to bypass the epithelial barrier in order to reach the fibroblastic
      core and induce disorganization of the spheroid structure. An increased cell
      death was observed in fibroblastic core. The development of such 3D model may be
      useful to define the role of EC-FB interactions on periodontal host-immune
      response and to assess the efficacy of new therapeutics.

PMID- 30297795
TI  - Applications of the new ESPEN definition of malnutrition and SARC-F in Chinese
      nursing home residents.
AB  - We aimed to compare the predictive capacity of malnutrition, sarcopenia, and
      malnutrition combined with sarcopenia for mortality in nursing home residents. We
      conducted a prospective study in four nursing homes in China. Nutrition status
      and sarcopenia were measured according to the new European Society of Clinical
      Nutrition and Metabolism (ESPEN) definition and SARC-F, respectively. The study
      population was divided into four groups: malnutrition with sarcopenia (MN+/SA+),
      malnutrition without sarcopenia (MN+/SA-), sarcopenia without malnutrition (MN
      /SA+), and normal nutrition without sarcopenia (MN-/SA-). The participants were
      followed up for 12 months. We included 329 participants. Thirty-eight
      participants (11.6%) had MN+/SA+, 38 participants (11.6%) had MN+/SA-, and 93
      participants (28.3%) had MN-/SA+. The 1-year mortality was 18.3%, 21.5%, 18.4%,
      and 47.4% in the MN-/SA-, MN-/SA+, MN+/SA-, and MN+/SA+ groups, respectively.
      Compared to participants with MN-/SA-, participants with MN+/SA+ were at a
      significantly higher risk of mortality (adjusted hazard ratio [HR]: 3.19, 95%
      confidence interval [CI] 1.71-5.95); however, MN-/SA+ (adjusted HR: 1.24, 95% CI
      0.69-2.22) and MN+/SA- (adjusted HR: 0.95, 95% CI 0.41-2.19) were not predictors
      of mortality. In conclusion, the coexistence of malnutrition and sarcopenia is a
      significant predictor of mortality in a study population of Chinese nursing home
      residents.

PMID- 30297796
TI  - The H3K9 methyltransferase SETDB1 maintains female identity in Drosophila germ
      cells.
AB  - The preservation of germ cell sexual identity is essential for gametogenesis.
      Here we show that H3K9me3-mediated gene silencing is integral to female fate
      maintenance in Drosophila germ cells. Germ cell specific loss of the H3K9me3
      pathway members, the H3K9 methyltransferase SETDB1, WDE, and HP1a, leads to
      ectopic expression of genes, many of which are normally expressed in testis.
      SETDB1 controls the accumulation of H3K9me3 over a subset of these genes without
      spreading into neighboring loci. At phf7, a regulator of male germ cell sexual
      fate, the H3K9me3 peak falls over the silenced testis-specific transcription
      start site. Furthermore, H3K9me3 recruitment to phf7 and repression of testis
      specific transcription is dependent on the female sex determination gene Sxl.
      Thus, female identity is secured by an H3K9me3 epigenetic pathway in which Sxl is
      the upstream female-specific regulator, SETDB1 is the required chromatin writer,
      and phf7 is one of the critical SETDB1 target genes.

PMID- 30297798
TI  - Battery-operated integrated frequency comb generator.
AB  - Optical frequency combs are broadband sources that offer mutually coherent,
      equidistant spectral lines with unprecedented precision in frequency and timing
      for an array of applications1. Frequency combs generated in microresonators
      through the Kerr nonlinearity require a single-frequency pump laser and have the
      potential to provide highly compact, scalable and power-efficient devices2,3.
      Here we demonstrate a device-a laser-integrated Kerr frequency comb generator
      that fulfils this potential through use of extremely low-loss silicon nitride
      waveguides that form both the microresonator and an integrated laser cavity. Our
      device generates low-noise soliton-mode-locked combs with a repetition rate of
      194 gigahertz at wavelengths near 1,550 nanometres using only 98 milliwatts of
      electrical pump power. The dual-cavity configuration that we use combines the
      laser and microresonator, demonstrating the flexibility afforded by close
      integration of these components, and together with the ultra low power
      consumption should enable production of highly portable and robust frequency and
      timing references, sensors and signal sources. This chip-based integration of
      microresonators and lasers should also provide tools with which to investigate
      the dynamics of comb and soliton generation.

PMID- 30297797
TI  - Structural insights into the electron/proton transfer pathways in the
      quinol:fumarate reductase from Desulfovibrio gigas.
AB  - The membrane-embedded quinol:fumarate reductase (QFR) in anaerobic bacteria
      catalyzes the reduction of fumarate to succinate by quinol in the anaerobic
      respiratory chain. The electron/proton-transfer pathways in QFRs remain
      controversial. Here we report the crystal structure of QFR from the anaerobic
      sulphate-reducing bacterium Desulfovibrio gigas (D. gigas) at 3.6 A resolution.
      The structure of the D. gigas QFR is a homo-dimer, each protomer comprising two
      hydrophilic subunits, A and B, and one transmembrane subunit C, together with six
      redox cofactors including two b-hemes. One menaquinone molecule is bound near
      heme bL in the hydrophobic subunit C. This location of the menaquinone-binding
      site differs from the menaquinol-binding cavity proposed previously for QFR from
      Wolinella succinogenes. The observed bound menaquinone might serve as an
      additional redox cofactor to mediate the proton-coupled electron transport across
      the membrane. Armed with these structural insights, we propose electron/proton
      transfer pathways in the quinol reduction of fumarate to succinate in the D.
      gigas QFR.

PMID- 30297799
TI  - A slow-cycling LGR5 tumour population mediates basal cell carcinoma relapse after
      therapy.
AB  - Basal cell carcinoma (BCC) is the most frequent cancer in humans and results from
      constitutive activation of the Hedgehog pathway1. Several Smoothened inhibitors
      are used to treat Hedgehog-mediated malignancies, including BCC and
      medulloblastoma2. Vismodegib, a Smoothened inhibitor, leads to BCC shrinkage in
      the majority of patients with BCC3, but the mechanism by which it mediates BCC
      regression is unknown. Here we used two genetically engineered mouse models of
      BCC4 to investigate the mechanisms by which inhibition of Smoothened mediates
      tumour regression. We found that vismodegib mediates BCC regression by inhibiting
      a hair follicle-like fate and promoting the differentiation of tumour cells.
      However, a small population of tumour cells persists and is responsible for
      tumour relapse following treatment discontinuation, mimicking the situation found
      in humans5. In both mouse and human BCC, this persisting, slow-cycling tumour
      population expresses LGR5 and is characterized by active Wnt signalling.
      Combining Lgr5 lineage ablation or inhibition of Wnt signalling with vismodegib
      treatment leads to eradication of BCC. Our results show that vismodegib induces
      tumour regression by promoting tumour differentiation, and demonstrates that the
      synergy between Wnt and Smoothened inhibitors is a clinically relevant strategy
      for overcoming tumour relapse in BCC.

PMID- 30297800
TI  - Exciton-polariton topological insulator.
AB  - Topological insulators-materials that are insulating in the bulk but allow
      electrons to flow on their surface-are striking examples of materials in which
      topological invariants are manifested in robustness against perturbations such as
      defects and disorder1. Their most prominent feature is the emergence of edge
      states at the boundary between areas with different topological properties. The
      observable physical effect is unidirectional robust transport of these edge
      states. Topological insulators were originally observed in the integer quantum
      Hall effect2 (in which conductance is quantized in a strong magnetic field) and
      subsequently suggested3-5 and observed6 to exist without a magnetic field, by
      virtue of other effects such as strong spin-orbit interaction. These were systems
      of correlated electrons. During the past decade, the concepts of topological
      physics have been introduced into other fields, including microwaves7,8, photonic
      systems9,10, cold atoms11,12, acoustics13,14 and even mechanics15. Recently,
      topological insulators were suggested to be possible in exciton-polariton
      systems16-18 organized as honeycomb (graphene-like) lattices, under the influence
      of a magnetic field. Exciton-polaritons are part-light, part-matter
      quasiparticles that emerge from strong coupling of quantum-well excitons and
      cavity photons19. Accordingly, the predicted topological effects differ from all
      those demonstrated thus far. Here we demonstrate experimentally an exciton
      polariton topological insulator. Our lattice of coupled semiconductor
      microcavities is excited non-resonantly by a laser, and an applied magnetic field
      leads to the unidirectional flow of a polariton wavepacket around the edge of the
      array. This chiral edge mode is populated by a polariton condensation mechanism.
      We use scanning imaging techniques in real space and Fourier space to measure
      photoluminescence and thus visualize the mode as it propagates. We demonstrate
      that the topological edge mode goes around defects, and that its propagation
      direction can be reversed by inverting the applied magnetic field. Our exciton
      polariton topological insulator paves the way for topological phenomena that
      involve light-matter interaction, amplification and the interaction of exciton
      polaritons as a nonlinear many-body system.

PMID- 30297801
TI  - A cell identity switch allows residual BCC to survive Hedgehog pathway
      inhibition.
AB  - Despite the efficacy of Hedgehog pathway inhibitors in the treatment of basal
      cell carcinoma (BCC)1, residual disease persists in some patients and may
      contribute to relapse when treatment is discontinued2. Here, to study the effect
      of the Smoothened inhibitor vismodegib on tumour clearance, we have used a Ptch1
      Trp53 mouse model of BCC3 and found that mice treated with vismodegib harbour
      quiescent residual tumours that regrow upon cessation of treatment. Profiling
      experiments revealed that residual BCCs initiate a transcriptional program that
      closely resembles that of stem cells of the interfollicular epidermis and
      isthmus, whereas untreated BCCs are more similar to the hair follicle bulge. This
      cell identity switch was enabled by a mostly permissive chromatin state
      accompanied by rapid Wnt pathway activation and reprogramming of super enhancers
      to drive activation of key transcription factors involved in cellular identity.
      Accordingly, treatment of BCC with both vismodegib and a Wnt pathway inhibitor
      reduced the residual tumour burden and enhanced differentiation. Our study
      identifies a resistance mechanism in which tumour cells evade treatment by
      adopting an alternative identity that does not rely on the original oncogenic
      driver for survival.

PMID- 30297802
TI  - Metallo-Curcumin-Conjugated DNA Complexes Induces Preferential Prostate Cancer
      Cells Cytotoxicity and Pause Growth of Bacterial Cells.
AB  - DNA nanotechnology can be used to create intricate DNA structures due to the
      ability to direct the molecular assembly of nanostructures through a bottom-up
      approach. Here, we propose nanocarriers composed of both synthetic and natural
      DNA for drug delivery. The topological, optical characteristics, and interaction
      studies of Cu2+/Ni2+/Zn2+-curcumin-conjugated DNA complexes were studied using
      atomic force microscopy (AFM), UV-vis spectroscopy, Fourier transform infrared
      and mass spectroscopy. The maximum release of metallo-curcumin conjugates from
      the DNA complexes, triggered by switching the pH, was found in an acidic medium.
      The bacterial growth curves of E. coli and B. subtilis displayed a prolonged lag
      phase when tested with the metallo-curcumin-conjugated DNA complexes. We also
      tested the in vitro cytotoxicity of the metallo-curcumin-conjugated DNA complexes
      to prostate cancer cells using an MTS assay, which indicated potent growth
      inhibition of the cells. Finally, we studied the cellular uptake of the
      complexes, revealing that DNA complexes with Cu2+/Ni2+-curcumin exhibited
      brighter fluorescence than those with Zn2+-curcumin.

PMID- 30297803
TI  - Dielectric Response of Quantum Critical Ferroelectric as a Function of Pressure.
AB  - In this work we report for the first time measurements of the dielectric loss of
      single-crystal SrTiO3 under the application of hydrostatic pressure up to 20 kbar
      and temperatures down to 200 mK which allow us to comment on the evolution of new
      fundamental material properties and their relationship with the recently
      discovered quantum critical phenomena in this material. The well known 18 K peak
      or shoulder was no longer observed after pressure was applied, even after
      subsequently removing it, suggesting it is associated with the twin walls formed
      at the 110 K cubic-tetragonal transition. The family of familiar peaks were all
      seen to increase in temperature linearly with pressure and the height of the 9.4
      K peak was drastically suppressed by even the smallest pressures. This peak is
      discussed in the context of a postulated ferroelectric quantum critical point in
      SrTiO3 and the behaviour of its size linked to the position of this point on the
      recently established phase diagram.

PMID- 30297804
TI  - MNK1 inhibitor CGP57380 overcomes mTOR inhibitor-induced activation of eIF4E: the
      mechanism of synergic killing of human T-ALL cells.
AB  - Although the treatment of adult T-cell acute lymphoblastic leukemia (T-ALL) has
      been significantly improved, the heterogeneous genetic landscape of the disease
      often causes relapse. Aberrant activation of mammalian target of rapamycin (mTOR)
      pathway in T-ALL is responsible for treatment failure and relapse, suggesting
      that mTOR inhibition may represents a new therapeutic strategy. In this study, we
      investigated whether the mTOR complex 1 (mTORC1) inhibitor everolimus could be
      used as a therapeutic agent against human T-ALL. We showed that rapamycin and its
      analog RAD001 (everolimus) exerted only mild inhibition on the viability of
      Jurkat, CEM and Molt-4 cell lines (for everolimus the maximum inhibition was <40%
      at 100 nM), but greatly enhanced the phosphorylation of eIF4E, a downstream
      substrate of MAPK-interacting kinase (MNK) that was involved in promoting cell
      survival. Furthermore, we demonstrated in Jurkat cells that mTOR inhibitor
      induced eIF4E phosphorylation was independent of insulin-like growth factor
      1/insulin-like growth factor-1 receptor axis, but was secondary to mTOR
      inhibition. Then we examined the antileukemia effects of CGP57380, a MNK1
      inhibitor, and we found that CGP57380 (4-16 MUM) dose-dependently suppressed the
      expression of both phosphor-MNK1 and phosphor-eIF4E, thereby inhibiting
      downstream targets such as c-Myc and survivin in T-ALL cells. Importantly,
      CGP57380 produced a synergistic growth inhibitory effect with everolimus in T-ALL
      cells, and treatment with this targeted therapy overcame everolimus-induced eIF4E
      phosphorylation. In conclusion, our results suggest that dual-targeting of mTOR
      and MNK1/eIF4E signaling pathways may represent a novel therapeutic strategy for
      the treatment of human T-ALL.

PMID- 30297805
TI  - Subtomogram averaging of COPII assemblies reveals how coat organization dictates
      membrane shape.
AB  - Eukaryotic cells employ membrane-bound carriers to transport cargo between
      compartments in a process essential to cell functionality. Carriers are generated
      by coat complexes that couple cargo capture to membrane deformation. The COPII
      coat mediates export from the endoplasmic reticulum by assembling in inner and
      outer layers, yielding carriers of variable shape and size that allow secretion
      of thousands of diverse cargo. Despite detailed understanding of COPII subunits,
      the molecular mechanisms of coat assembly and membrane deformation are unclear.
      Here we present a 4.9 A cryo-tomography subtomogram averaging structure of in
      vitro-reconstituted membrane-bound inner coat. We show that the outer coat (Sec13
      Sec31) bridges inner coat subunits (Sar1-Sec23-Sec24), promoting their assembly
      into a tight lattice. We directly visualize the membrane-embedded Sar1
      amphipathic helix, revealing that lattice formation induces parallel helix
      insertions, yielding tubular curvature. We propose that regulators like the
      procollagen receptor TANGO1 modulate this mechanism to determine vesicle shape
      and size.

PMID- 30297806
TI  - LINCS L1000 dataset-based repositioning of CGP-60474 as a highly potent anti
      endotoxemic agent.
AB  - Sepsis is one of the most common clinical syndromes that causes death and
      disability. Although many studies have developed drugs for sepsis treatment, none
      have decreased the mortality rate. The aim of this study was to identify a novel
      treatment option for sepsis using the library of integrated network-based
      cellular signatures (LINCS) L1000 perturbation dataset based on an in vitro and
      in vivo sepsis model. Sepsis-related microarray studies of early-stage
      inflammatory processes in patients and innate immune cells were collected from
      the Gene Expression Omnibus (GEO) data repository and used for candidate drug
      selection based on the LINCS L1000 perturbation dataset. The anti-inflammatory
      effects of the selected candidate drugs were analyzed using activated macrophage
      cell lines. CGP-60474, an inhibitor of cyclin-dependent kinase, was the most
      potent drug. It alleviated tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) in activated macrophages by downregulating the NF-kappaB
      activity, and it reduced the mortality rate in LPS induced endotoxemia mice. This
      study shows that CGP-60474 could be a potential therapeutic candidate to
      attenuate the endotoxemic process. Additionally, the virtual screening strategy
      using the LINCS L1000 perturbation dataset could be a cost and time effective
      tool in the early stages of drug development.

PMID- 30297807
TI  - Integration of gene expression and brain-wide connectivity reveals the multiscale
      organization of mouse hippocampal networks.
AB  - Understanding the organization of the hippocampus is fundamental to understanding
      brain function related to learning, memory, emotions, and diseases such as
      Alzheimer's disease. Physiological studies in humans and rodents have suggested
      that there is both structural and functional heterogeneity along the longitudinal
      axis of the hippocampus. However, the recent discovery of discrete gene
      expression domains in the mouse hippocampus has provided the opportunity to re
      evaluate hippocampal connectivity. To integrate mouse hippocampal gene expression
      and connectivity, we mapped the distribution of distinct gene expression patterns
      in mouse hippocampus and subiculum to create the Hippocampus Gene Expression
      Atlas (HGEA). Notably, previously unknown subiculum gene expression patterns
      revealed a hidden laminar organization. Guided by the HGEA, we constructed the
      most detailed hippocampal connectome available using Mouse Connectome Project (
      http://www.mouseconnectome.org ) tract tracing data. Our results define the
      hippocampus' multiscale network organization and elucidate each subnetwork's
      unique brain-wide connectivity patterns.

PMID- 30297809
TI  - Portable low-cost instrumentation for monitoring Rayleigh scattering from
      chemical sensors based on metallic nanoparticles.
AB  - Using a Hg(II) sensor based on the aggregation of gold nanoparticles as a model
      system, we evaluated the performance of two portable low-cost devices that
      monitor the wavelength-ratiometric resonance Rayleigh scattering signal of the
      chemical sensor upon white-LED illumination. The first device uses two optical
      filter-photodiode combinations to detect scattered light while the second employs
      a novel ultra-compact (grating-free) spectral sensor. Results show that the
      response of the Hg(II) sensor monitored with these devices is comparable to that
      measured using a high-end benchtop scanning spectrofluorometer. The great
      potential of this new LED-spectral sensor was demonstrated with the
      quantification of Hg(II) in tap and spring water. Due to the promising results
      obtained, many reported chemical sensors based on Rayleigh scattering from
      metallic nanoparticles could take advantage of this compact portable
      instrumentation for cost-effective field-deployable applications.

PMID- 30297808
TI  - Epigenomic map of human liver reveals principles of zonated morphogenic and
      metabolic control.
AB  - A deeper epigenomic understanding of spatial organization of cells in human
      tissues is an important challenge. Here we report the first combined positional
      analysis of transcriptomes and methylomes across three micro-dissected zones
      (pericentral, intermediate and periportal) of human liver. We identify pronounced
      anti-correlated transcriptional and methylation gradients including a core of 271
      genes controlling zonated metabolic and morphogen networks and observe a
      prominent porto-central gradient of DNA methylation at binding sites of 46
      transcription factors. The gradient includes an epigenetic and transcriptional
      Wnt signature supporting the concept of a pericentral hepatocyte regeneration
      pathway under steady-state conditions. While donors with non-alcoholic fatty
      liver disease show consistent gene expression differences corresponding to the
      severity of the disease across all zones, the relative zonated gene expression
      and DNA methylation patterns remain unchanged. Overall our data provide a wealth
      of new positional insights into zonal networks controlled by epigenetic and
      transcriptional gradients in human liver.

PMID- 30297811
TI  - Transparency revealed.

PMID- 30297812
TI  - Polarity governs atomic interaction through two-dimensional materials.
AB  - The transparency of two-dimensional (2D) materials to intermolecular interactions
      of crystalline materials has been an unresolved topic. Here we report that remote
      atomic interaction through 2D materials is governed by the binding nature, that
      is, the polarity of atomic bonds, both in the underlying substrates and in 2D
      material interlayers. Although the potential field from covalent-bonded materials
      is screened by a monolayer of graphene, that from ionic-bonded materials is
      strong enough to penetrate through a few layers of graphene. Such field
      penetration is substantially attenuated by 2D hexagonal boron nitride, which
      itself has polarization in its atomic bonds. Based on the control of
      transparency, modulated by the nature of materials as well as interlayer
      thickness, various types of single-crystalline materials across the periodic
      table can be epitaxially grown on 2D material-coated substrates. The epitaxial
      films can subsequently be released as free-standing membranes, which provides
      unique opportunities for the heterointegration of arbitrary single-crystalline
      thin films in functional applications.

PMID- 30297813
TI  - Programmed assembly of synthetic protocells into thermoresponsive prototissues.
AB  - Although several new types of synthetic cell-like entities are now available,
      their structural integration into spatially interlinked prototissues that
      communicate and display coordinated functions remains a considerable challenge.
      Here we describe the programmed assembly of synthetic prototissue constructs
      based on the bio-orthogonal adhesion of a spatially confined binary community of
      protein-polymer protocells, termed proteinosomes. The thermoresponsive properties
      of the interlinked proteinosomes are used collectively to generate prototissue
      spheroids capable of reversible contractions that can be enzymatically modulated
      and exploited for mechanochemical transduction. Overall, our methodology opens up
      a route to the fabrication of artificial tissue-like materials capable of
      collective behaviours, and addresses important emerging challenges in bottom-up
      synthetic biology and bioinspired engineering.

PMID- 30297810
TI  - Ultrasmall targeted nanoparticles with engineered antibody fragments for imaging
      detection of HER2-overexpressing breast cancer.
AB  - Controlling the biodistribution of nanoparticles upon intravenous injection is
      the key to achieving target specificity. One of the impediments in nanoparticle
      based tumor targeting is the inability to limit the trafficking of nanoparticles
      to liver and other organs leading to smaller accumulated amounts in tumor
      tissues, particularly via passive targeting. Here we overcome both these
      challenges by designing nanoparticles that combine the specificity of antibodies
      with favorable particle biodistribution profiles, while not exceeding the
      threshold for renal filtration as a combined vehicle. To that end, ultrasmall
      silica nanoparticles are functionalized with anti-human epidermal growth factor
      receptor 2 (HER2) single-chain variable fragments to exhibit high tumor-targeting
      efficiency and efficient renal clearance. This ultrasmall targeted
      nanotheranostics/nanotherapeutic platform has broad utility, both for imaging a
      variety of tumor tissues by suitably adopting the targeting fragment and as a
      potentially useful drug delivery vehicle.

PMID- 30297814
TI  - Interparticle hydrogen bonding can elicit shear jamming in dense suspensions.
AB  - Dense suspensions of hard particles in a liquid can exhibit strikingly counter
      intuitive behaviour, such as discontinuous shear thickening (DST)1-7 and
      reversible shear jamming (SJ) into a state where flow is arrested and the
      suspension is solid-like8-12. A stress-activated crossover from hydrodynamic
      interactions to frictional particle contacts is key for these behaviours2
      4,6,7,9,13. However, in experiments, many suspensions show only DST, not SJ. Here
      we show that particle surface chemistry plays a central role in creating
      conditions that make SJ readily observable. We find the system's ability to form
      interparticle hydrogen bonds when sheared into contact elicits SJ. We demonstrate
      this with charge-stabilized polymer microspheres and non-spherical cornstarch
      particles, controlling hydrogen bond formation with solvents. The propensity for
      SJ is quantified by tensile tests12 and linked to an enhanced friction by atomic
      force microscopy. Our results extend the fundamental understanding of the SJ
      mechanism and open avenues for designing strongly non-Newtonian fluids.

PMID- 30297815
TI  - Gaseous flow through heterogeneous, partially connected networks of pipes.
AB  - Simulations of flow of an ideal gas through heterogeneous simple cubic pipe
      networks with different pipe radius distributions and variable bond coordination
      numbers were performed. Networks with monomodal and bimodal radius distributions
      were constructed. A very wide range of Knudsen numbers was achieved. Flow
      simulations of purely viscous gases and incompressible liquids were also carried
      out for comparison. The permeability to gas in the purely viscous regime was
      larger than the permeability to an incompressible liquid. Based on a variety of
      computational tests, this result was likely not a numerical artifact. The
      simulated macroscopic flow behavior differed from the underlying single pipe
      model, depending on the radius distribution, network connectivity and magnitude
      of the externally applied pressure gradient, and was compatible with the
      Klinkenberg analysis only when the maximum Knudsen number used in each simulation
      was lower than 1. In this condition, the Klinkenberg coefficient was nearly
      proportional to the inverse of the network hydraulic radius while the effect of
      the radius distribution was weak and that of the network connectivity essentially
      negligible. The bimodal simulations displayed a typical percolation behavior,
      with the Klinkenberg coefficient remaining constant as long as the large pipe
      population was connected.

PMID- 30297817
TI  - A plug-and-play approach for malaria vaccination.

PMID- 30297818
TI  - A malaria vaccine adjuvant based on recombinant antigen binding to liposomes.
AB  - Pfs25 is a malaria transmission-blocking vaccine antigen candidate, but its
      apparently limited immunogenicity in humans has hindered clinical development.
      Here, we show that recombinant, polyhistidine-tagged (his-tagged) Pfs25 can be
      mixed at the time of immunization with pre-formed liposomes containing cobalt
      porphyrin-phospholipid, resulting in spontaneous nanoliposome antigen
      particleization (SNAP). Antigens are stably presented in uniformly orientated
      display via his-tag insertion in the cobalt porphyrin-phospholipid bilayer,
      without covalent modification or disruption of antigen conformation. SNAP
      immunization of mice and rabbits is well tolerated with minimal local
      reactogenicity, and results in orders-of-magnitude higher functional antibody
      generation compared with other 'mix-and-inject' adjuvants. Serum-stable antigen
      binding during transit to draining lymph nodes leads to enhanced antigen uptake
      by phagocytic antigen-presenting cells, with subsequent generation of long-lived,
      antigen-specific plasma cells. Seamless multiplexing with four additional his
      tagged Plasmodium falciparum polypeptides induces strong and balanced antibody
      production, illustrating the simplicity of developing multistage particulate
      vaccines with SNAP immunization.

PMID- 30297816
TI  - Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Novel Potential Biomarker in
      Gastroenteropancreatic Neuroendocrine Tumors.
AB  - OBJECTIVES: The association between the presence and alterations of the
      components of the ghrelin system and the development and progression of
      neuroendocrine tumors (NETs) is still controversial and remains unclear. METHODS:
      Here, we systematically evaluated the expression levels (by quantitative-PCR) of
      key ghrelin system components of in gastroenteropancreatic (GEP)-NETs, as
      compared to non-tumor adjacent (NTA; n = 42) and normal tissues (NT; n = 14).
      Then, we analyzed their putative associations with clinical-histological
      characteristics. RESULTS: The results indicate that ghrelin and its receptor
      GHSR1a are present in a high proportion of normal tissues, while the enzyme
      ghrelin-O-acyltransferase (GOAT) and the splicing variants In1-ghrelin and GHSR1b
      were present in a lower proportion of normal tissues. In contrast, all ghrelin
      system components were present in a high proportion of tumor and NTA tissues.
      GOAT was significantly overexpressed (by quantitative-PCR (qPCR)) in tumor
      samples compared to NTA, while a trend was found for ghrelin, In1-ghrelin and
      GHSR1a. In addition, expression of these components displayed significant
      correlations with key clinical parameters. The marked overexpression of GOAT in
      tumor samples compared to NTA regions was confirmed by IHC, revealing that this
      enzyme is particularly overexpressed in gastrointestinal NETs, where it is
      directly correlated with tumor diameter. CONCLUSIONS: These results provide novel
      information on the presence and potential pathophysiological implications of the
      ghrelin system components in GEP-NETs, wherein GOAT might represent a novel
      diagnostic biomarker.

PMID- 30297819
TI  - Intracellular speciation of gold nanorods alters the conformational dynamics of
      genomic DNA.
AB  - Gold nanorods are one of the most widely explored inorganic materials in
      nanomedicine for diagnostics, therapeutics and sensing1. It has been shown that
      gold nanorods are not cytotoxic and localize within cytoplasmic vesicles
      following endocytosis, with no nuclear localization2,3, but other studies have
      reported alterations in gene expression profiles in cells following exposure to
      gold nanorods, via unknown mechanisms4. In this work we describe a pathway that
      can contribute to this phenomenon. By mapping the intracellular chemical
      speciation process of gold nanorods, we show that the commonly used Au-thiol
      conjugation, which is important for maintaining the noble (inert) properties of
      gold nanostructures, is altered following endocytosis, resulting in the formation
      of Au(I)-thiolates that localize in the nucleus5. Furthermore, we show that
      nuclear localization of the gold species perturbs the dynamic microenvironment
      within the nucleus and triggers alteration of gene expression in human cells. We
      demonstrate this using quantitative visualization of ubiquitous DNA G-quadruplex
      structures, which are sensitive to ionic imbalances, as an indicator of the
      formation of structural alterations in genomic DNA.

PMID- 30297820
TI  - Ice rule fragility via topological charge transfer in artificial colloidal ice.
AB  - Artificial particle ices are model systems of constrained, interacting particles.
      They have been introduced theoretically to study ice-manifolds emergent from
      frustration, along with domain wall and grain boundary dynamics, doping, pinning
      depinning, controlled transport of topological defects, avalanches, and memory
      effects. Recently such particle-based ices have been experimentally realized with
      vortices in nano-patterned superconductors or gravitationally trapped colloids.
      Here we demonstrate that, although these ices are generally considered equivalent
      to magnetic spin ices, they can access a novel spectrum of phenomenologies that
      are inaccessible to the latter. With experiments, theory and simulations we
      demonstrate that in mixed coordination geometries, entropy-driven negative
      monopoles spontaneously appear at a density determined by the vertex-mixture
      ratio. Unlike its spin-based analogue, the colloidal system displays a "fragile
      ice" manifold, where local energetics oppose the ice rule, which is instead
      enforced through conservation of the global topological charge. The fragile
      colloidal ice, stabilized by topology, can be spontaneously broken by topological
      charge transfer.

PMID- 30297821
TI  - High-efficiency optogenetic silencing with soma-targeted anion-conducting
      channelrhodopsins.
AB  - Optogenetic silencing allows time-resolved functional interrogation of defined
      neuronal populations. However, the limitations of inhibitory optogenetic tools
      impose stringent constraints on experimental paradigms. The high light power
      requirement of light-driven ion pumps and their effects on intracellular ion
      homeostasis pose unique challenges, particularly in experiments that demand
      inhibition of a widespread neuronal population in vivo. Guillardia theta anion
      conducting channelrhodopsins (GtACRs) are promising in this regard, due to their
      high single-channel conductance and favorable photon-ion stoichiometry. However,
      GtACRs show poor membrane targeting in mammalian cells, and the activity of such
      channels can cause transient excitation in the axon due to an excitatory chloride
      reversal potential in this compartment. Here, we address these problems by
      enhancing membrane targeting and subcellular compartmentalization of GtACRs. The
      resulting soma-targeted GtACRs show improved photocurrents, reduced axonal
      excitation and high light sensitivity, allowing highly efficient inhibition of
      neuronal activity in the mammalian brain.

PMID- 30297822
TI  - Predicting El Nino Beyond 1-year Lead: Effect of the Western Hemisphere Warm
      Pool.
AB  - Due to the profound impact of El Nino-Southern Oscillation (ENSO) on global
      climate and weather, extensive research has been devoted to its prediction.
      However, prediction accuracy based on observation is still insufficient and
      largely limited to less than one year of lead time. In this study, we demonstrate
      the possibility that anomalous sea surface temperature (SST) warming (cooling) in
      the Western Hemisphere Warm Pool (WHWP, a.k.a. Atlantic Warm Pool) near the Intra
      Americas Sea (IAS), which is the second largest warm pool on the planet,
      contributes to the initiation of La Nina (El Nino) with a 17-month lag time. SST
      anomalies in WHWP in late boreal summer contribute significantly to the emergence
      of the Pacific meridional mode (PMM) via interaction between the ocean and
      atmosphere over the subtropical North Pacific during the subsequent winter and
      spring. Near-equatorial surface wind anomalies associated with the PMM can
      further trigger ENSO through the dynamics of the equatorial oceanic waves. Thus,
      this observational analysis presents a clear step-by-step explanation about the
      influence of WHWP on ENSO development with a 17-month lead time.

PMID- 30297825
TI  - Evolutionary changes in growth, regrowth and carbohydrate storage in an invasive
      plant.
AB  - We hypothesized that due to the absence of specialist herbivores in introduced
      ranges, invasive plants have evolved decreased allocation to carbohydrate storage
      for regrowth ability and as a consequence allocate more to growth. In this study,
      we compared plant growth, carbohydrate storage and regrowth ability of invasive
      and native Jacobaea vulgaris in response to complete shoot defoliation. We used
      invasive J. vulgaris genotypes from three geographically and climactically
      distinct regions and compared these with native genotypes from Europe. We found
      that invasive genotypes initially grew larger while native genotypes regrew
      larger after defoliation. Before defoliation, the carbohydrate storage in roots
      of invasive genotypes was 38% lower than native genotypes. Biomass after regrowth
      increased with root carbohydrate storage while it decreased with structural root
      mass, showing that it is crucial to study root storage and structural components
      separately in order to investigate plant regrowth. All studied traits of invasive
      populations from the three geographically and climatologically distinct regions
      changed in the same expected direction suggesting that the shifts in herbivore
      guild were causal to the observed change in growth and regrowth ability rather
      than environmental factors.

PMID- 30297823
TI  - Rifamycin congeners kanglemycins are active against rifampicin-resistant bacteria
      via a distinct mechanism.
AB  - Rifamycin antibiotics (Rifs) target bacterial RNA polymerases (RNAPs) and are
      widely used to treat infections including tuberculosis. The utility of these
      compounds is threatened by the increasing incidence of resistance (RifR). As
      resistance mechanisms found in clinical settings may also occur in natural
      environments, here we postulated that bacteria could have evolved to produce
      rifamycin congeners active against clinically relevant resistance phenotypes. We
      survey soil metagenomes and identify a tailoring enzyme-rich family of gene
      clusters encoding biosynthesis of rifamycin congeners (kanglemycins, Kangs) with
      potent in vivo and in vitro activity against the most common clinically relevant
      RifR mutations. Our structural and mechanistic analyses reveal the basis for Kang
      inhibition of RifR RNAP. Unlike Rifs, Kangs function through a mechanism that
      includes interfering with 5'-initiating substrate binding. Our results suggest
      that examining soil microbiomes for new analogues of clinically used antibiotics
      may uncover metabolites capable of circumventing clinically important resistance
      mechanisms.

PMID- 30297824
TI  - The experience of vivid autobiographical reminiscence is supported by subjective
      content representations in the precuneus.
AB  - The human posteromedial cortex, which includes core regions of the default mode
      network (DMN), is thought to play an important role in episodic memory. However,
      the nature and functional role of representations in these brain regions remain
      unspecified. Nine participants (all female) wore smartphone devices to record
      episodes from their daily lives for multiple weeks, each night indicating the
      personally-salient attributes of each episode. Participants then relived their
      experiences in an fMRI scanner cued by images from their own lives.
      Representational Similarity Analysis revealed a broad network, including parts of
      the DMN, that represented personal semantics during autobiographical
      reminiscence. Within this network, activity in the right precuneus reflected more
      detailed representations of subjective contents during vivid relative to non
      vivid, recollection. Our results suggest a more specific mechanism underlying the
      phenomenology of vivid autobiographical reminiscence, supported by rich
      subjective content representations in the precuneus, a hub of the DMN previously
      implicated in metacognitive evaluations during memory retrieval.

PMID- 30297826
TI  - Microscale heat transfer and thermal extinction of a wire-grid polarizer.
AB  - We explore heat transfer and thermal characteristics of a wire-grid polarizer
      (WGP) on a microscale by investigating the effect of various geometrical
      parameters such as wire-grid period, height, and a fill factor. The thermal
      properties arise from heat transfer by light absorption and conduction in wire
      grids. Fill factor was found to be the most dominant geometrical parameter. For
      TM polarized light, a higher fill factor with thicker wire-grids increased the
      temperature. The local temperature was found to rise up to Tmax = 354.5 K. TE
      polarization tended to produce lower temperature. Thermal extinction due to
      polarimetric extinction by a WGP was also evaluated and highest extinction was
      observed to be 4.78 dB, which represents a temperature difference DeltaT = 54.3 
      degrees C. We expect the results to be useful for WGPs in polarization-sensitive
      thermal switching applications.

PMID- 30297828
TI  - TGF-beta2 downregulates osteogenesis under inflammatory conditions in dental
      follicle stem cells.
AB  - Bone formation is important for the reconstruction of bone-related structures in
      areas that have been damaged by inflammation. Inflammatory conditions such as
      those that occur in patients with rheumatoid arthritis, cystic fibrosis, and
      periodontitis have been shown to inhibit osteoblastic differentiation. This study
      focussed on dental follicle stem cells (DFSCs), which are found in developing
      tooth germ and participate in the reconstruction of alveolar bone and periodontal
      tissue in periodontal disease. After bacterial infection of inflamed dental
      tissue, the destruction of bone was observed. Currently, little is known about
      the relationship between the inflammatory environment and bone formation.
      Osteogenic differentiation of inflamed DFSCs resulted in decreased alkaline
      phosphatase (ALP) activity and alizarin red S staining compared to normal DFSCs.
      Additionally, in vivo transplantation of inflamed and normal DFSCs demonstrated
      severe impairment of osteogenesis by inflamed DFSCs. Protein profile analysis via
      liquid chromatography coupled with tandem mass spectrometry was performed to
      analyse the differences in protein expression in inflamed and normal tissue.
      Comparison of inflamed and normal DFSCs showed significant changes in the level
      of expression of transforming growth factor (TGF)-beta2. Porphyromonas gingivalis
      (P.g.)-derived lipopolysaccharide (LPS) was used to create in vitro inflammatory
      conditions similar to periodontitis. The osteogenic differentiation of LPS
      treated DFSCs was suppressed, and the cells displayed low levels of TGF-beta1 and
      high levels of TGF-beta2. DFSCs treated with TGF-beta2 inhibitors showed
      significant increases in alizarin red S staining and ALP activity. TGF-beta1
      expression was also increased after inhibition of TGF-beta2. By examining
      inflamed DFSCs and LPS-triggered DFSCs, these studies showed both clinically and
      experimentally that the increase in TGF-beta2 levels that occurs under
      inflammatory conditions inhibits bone formation.

PMID- 30297827
TI  - Melatonin inhibits attention-deficit/hyperactivity disorder caused by atopic
      dermatitis-induced psychological stress in an NC/Nga atopic-like mouse model.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease with the hallmark
      characteristics of pruritus, psychological stress, and sleep disturbance, all
      possibly associated with an increased risk of attention-deficit/hyperactivity
      disorder (ADHD). However, the etiology of the possible association between AD and
      ADHD is still not well understood. 2,4-dinitrochlorobenzene or corticosterone was
      used to evaluate the atopic symptom and its psychologic stress in the atopic mice
      model. Melatonin, corticotropin-releasing hormone, corticotropin-releasing
      hormone receptor, urocortin, proopiomelanocortin, adrenocorticotropic hormone,
      corticosterone, cAMP, cAMP response element-binding protein, dopamine and
      noradrenaline were analyzed spectrophotometrically, and the expression of
      dopamine beta-hydroxylase and tyrosine hydroxylase were measured by Western
      blotting or immunohistochemistry. AD-related psychological stress caused an
      increase in the levels of dopamine beta-hydroxylase and tyrosine hydroxylase,
      degradation of melatonin, hyper-activity of the hypothalamic-pituitary-adrenal
      axis, and dysregulation of dopamine and noradrenaline levels (ADHD phenomena) in
      the locus coeruleus, prefrontal cortex, and striatum of the AD mouse brain.
      Notably, melatonin administration inhibited the development of ADHD phenomena and
      their-related response in the mouse model. This study demonstrated that AD
      related psychological stress increased catecholamine dysfunction and accelerated
      the development of psychiatric comorbidities, such as ADHD.

PMID- 30297830
TI  - Chlorophyll a/b binding-specificity in water-soluble chlorophyll protein.
AB  - We altered the chlorophyll (Chl) binding sites in various versions of water
      soluble chlorophyll protein (WSCP) by amino acid exchanges to alter their
      preferences for either Chl a or Chl b. WSCP is ideally suited for this mutational
      analysis since it forms a tetrameric complex with only four identical Chl binding
      sites. A loop of 4-6 amino acids is responsible for Chl a versus Chl b
      selectivity. We show that a single amino acid exchange within this loop changes
      the relative Chl a/b affinities by a factor of 40. We obtained crystal structures
      of this WSCP variant binding either Chl a or Chl b. The Chl binding sites in
      these structures were compared with those in the major light-harvesting complex
      (LHCII) of the photosynthetic apparatus in plants to search for similar
      structural features involved in Chl a/b binding specificity.

PMID- 30297831
TI  - NIN interacts with NLPs to mediate nitrate inhibition of nodulation in Medicago
      truncatula.
AB  - Legume plants can assimilate inorganic nitrogen and have access to fixed nitrogen
      through symbiotic interaction with diazotrophic bacteria called rhizobia.
      Symbiotic nitrogen fixation is an energy-consuming process and is strongly
      inhibited when sufficient levels of fixed nitrogen are available, but the
      molecular mechanisms governing this regulation are largely unknown. The
      transcription factor nodule inception (NIN) is strictly required for nodulation
      and belongs to a family of NIN-like proteins (NLPs), which have been implicated
      in the regulation of nitrogen homeostasis in Arabidopsis. Here, we show that
      mutation or downregulation of NLP genes prevents nitrate inhibition of infection,
      nodule formation and nitrogen fixation. We find that NIN and NLPs physically
      interact through their carboxy-terminal PB1 domains. Furthermore, we find that
      NLP1 is required for the expression of nitrate-responsive genes and that nitrate
      triggers NLP1 re-localization from the cytosol to the nucleus. Finally, we show
      that NLP1 can suppress NIN activation of CRE1 expression in Nicotiana benthamiana
      and Medicago truncatula. Our findings highlight a central role for NLPs in the
      suppression of nodulation by nitrate.

PMID- 30297829
TI  - Notch1 regulates the initiation of metastasis and self-renewal of Group 3
      medulloblastoma.
AB  - Medulloblastoma is the most common malignant brain tumor of childhood. Group 3
      medulloblastoma, the most aggressive molecular subtype, frequently disseminates
      through the leptomeningeal cerebral spinal fluid (CSF) spaces in the brain and
      spinal cord. The mechanism of dissemination through the CSF remains poorly
      understood, and the molecular pathways involved in medulloblastoma metastasis and
      self-renewal are largely unknown. Here we show that NOTCH1 signaling pathway
      regulates both the initiation of metastasis and the self-renewal of
      medulloblastoma. We identify a mechanism in which NOTCH1 activates BMI1 through
      the activation of TWIST1. NOTCH1 expression and activity are directly related to
      medulloblastoma metastasis and decreased survival rate of tumor-bearing mice.
      Finally, medulloblastoma-bearing mice intrathecally treated with anti-NRR1, a
      NOTCH1 blocking antibody, present lower frequency of spinal metastasis and higher
      survival rate. These findings identify NOTCH1 as a pivotal driver of Group 3
      medulloblastoma metastasis and self-renewal, supporting the development of
      therapies targeting this pathway.

PMID- 30297832
TI  - Simple ruthenium-catalyzed reductive amination enables the synthesis of a broad
      range of primary amines.
AB  - The production of primary benzylic and aliphatic amines, which represent
      essential feedstocks and key intermediates for valuable chemicals, life science
      molecules and materials, is of central importance. Here, we report the synthesis
      of this class of amines starting from carbonyl compounds and ammonia by Ru
      catalyzed reductive amination using H2. Key to success for this synthesis is the
      use of a simple RuCl2(PPh3)3 catalyst that empowers the synthesis of >90 various
      linear and branched benzylic, heterocyclic, and aliphatic amines under
      industrially viable and scalable conditions. Applying this catalyst, -NH2 moiety
      has been introduced in functionalized and structurally diverse compounds, steroid
      derivatives and pharmaceuticals. Noteworthy, the synthetic utility of this Ru
      catalyzed amination protocol has been demonstrated by upscaling the reactions up
      to 10 gram-scale syntheses. Furthermore, in situ NMR studies were performed for
      the identification of active catalytic species. Based on these studies a
      mechanism for Ru-catalyzed reductive amination is proposed.

PMID- 30297833
TI  - Mannich base limits Candida albicans virulence by inactivating Ras-cAMP-PKA
      pathway.
AB  - Mannich bases and its derivatives are regarded as supreme pharmacophores in
      therapeutics. The study investigates the antimycotic potential of Mannich bases,
      1-((1H-benzimidazol-1-yl) methyl) urea (C1) and 1-((3-hydroxynapthalen-2-yl)
      methyl) thiourea (C2), against Candida albicans. Biofilm and hyphal inhibitory
      activities of the Mannich bases were tested by crystal violet quantification,
      fluorescence imaging cAMP rescue, qRT PCR, and by molecular docking analysis. The
      compounds inhibited the biofilms of C. albicans and restrained the filamentation
      abilities of the pathogen. Structure-activity relationship studies revealed that
      the presence of urea or thiourea moiety in the tail section is essential for
      interacting with adenylate cyclase (AC). The Mannich bases seemed to block Ras
      cAMP-PKA pathway by inhibiting second messenger activity required for hyphal
      induction and biofilm formation. In conclusion, the study warrants point-of-care
      testing of C1/C2 and provides a starting point for deriving several structurally
      modified Mannich bases which might plausibly replace the prevailing antimycotic
      drugs in future.

PMID- 30297835
TI  - Publisher Correction: Evidence linking microRNA suppression of essential
      prosurvival genes with hippocampal cell death after traumatic brain injury.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30297834
TI  - Effect of a butyrate-fortified milk replacer on gastrointestinal microbiota and
      products of fermentation in artificially reared dairy calves at weaning.
AB  - Enrichment of calf diets with exogenous butyrate has shown promise as a promotor
      of calf growth and intestinal development. However, the impact of dietary derived
      butyrate on the gut microbiota and their potential role, in turn, as mediators of
      its effect on calf growth and development is not known. Here, the effects of
      butyrate supplementation on rumen and hindgut microbiota and fermentation
      profiles were assessed in 16 Holstein-Friesian bull calves randomly assigned to
      one of two groups: Control (CON) fed conventional milk replacer or Sodium
      Butyrate (SB - added to milk replacer) from days 7 to 56 of life. In the colon,
      total short chain fatty acid (SCFA), propionate and acetate concentrations were
      increased by SB (P < 0.05). 16S rRNA gene amplicon sequencing showed cecal
      abundance of butyrate producers Butyrivibrio and Shuttleworthia were decreased by
      SB (P < 0.05), while that of the propionate producer Phascolarctobacterium was
      higher (P < 0.05). Mogibacterium is associated with impaired gut health and was
      reduced in the cecum of SB calves (P < 0.05). These data show that the beneficial
      effects of SB on growth and performance occur in tandem with changes in the
      abundance of important SCFA producing and health-associated bacteria in the
      hindgut in milk-fed calves.

PMID- 30297836
TI  - Haplosaurus computes protein haplotypes for use in precision drug design.
AB  - Selecting the most appropriate protein sequences is critical for precision drug
      design. Here we describe Haplosaurus, a bioinformatic tool for computation of
      protein haplotypes. Haplosaurus computes protein haplotypes from pre-existing
      chromosomally-phased genomic variation data. Integration into the Ensembl
      resource provides rapid and detailed protein haplotypes retrieval. Using
      Haplosaurus, we build a database of unique protein haplotypes from the 1000
      Genomes dataset reflecting real-world protein sequence variability and their
      prevalence. For one in seven genes, their most common protein haplotype differs
      from the reference sequence and a similar number differs on their most common
      haplotype between human populations. Three case studies show how knowledge of the
      range of commonly encountered protein forms predicted in populations leads to
      insights into therapeutic efficacy. Haplosaurus and its associated database is
      expected to find broad applications in many disciplines using protein sequences
      and particularly impactful for therapeutics design.

PMID- 30297837
TI  - Formation of the beta-barrel assembly machinery complex in lipid bilayers as seen
      by solid-state NMR.
AB  - The beta-barrel assembly machinery (BAM) is a pentameric complex (BamA-E), which
      catalyzes the essential process of beta-barrel protein insertion into the outer
      membrane of E. coli. Thus far, a detailed understanding of the insertion
      mechanism has been elusive but recent results suggest that local protein motion,
      in addition to the surrounding membrane environment, may be of critical
      relevance. We have devised a high-sensitivity solid-state NMR approach to
      directly probe protein motion and the structural changes associated with BAM
      complex assembly in lipid bilayers. Our results reveal how essential BamA
      domains, such as the interface formed by the polypeptide transport associated
      domains P4 and P5 become stabilized after complex formation and suggest that BamA
      beta-barrel opening and P5 reorientation is directly related to complex formation
      in membranes. Both the lateral gate, as well as P5, exhibit local dynamics, a
      property that could play an integral role in substrate recognition and insertion.

PMID- 30297838
TI  - C16-ceramide is a natural regulatory ligand of p53 in cellular stress response.
AB  - Ceramides are important participants of signal transduction, regulating
      fundamental cellular processes. Here we report the mechanism for activation of
      p53 tumor suppressor by C16-ceramide. C16-ceramide tightly binds within the p53
      DNA-binding domain (Kd ~ 60 nM), in close vicinity to the Box V motif. This
      interaction is highly selective toward the ceramide acyl chain length with its
      C10 atom being proximal to Ser240 and Ser241. Ceramide binding stabilizes p53 and
      disrupts its complex with E3 ligase MDM2 leading to the p53 accumulation, nuclear
      translocation and activation of the downstream targets. This mechanism of p53
      activation is fundamentally different from the canonical p53 regulation through
      protein-protein interactions or posttranslational modifications. The discovered
      mechanism is triggered by serum or folate deprivation implicating it in the
      cellular response to nutrient/metabolic stress. Our study establishes C16
      ceramide as a natural small molecule activating p53 through the direct binding.

PMID- 30297839
TI  - An Evolutionarily Conserved Mesodermal Enhancer in Vertebrate Zic3.
AB  - Zic3 encodes a zinc finger protein essential for the development of meso
      ectodermal tissues. In mammals, Zic3 has important roles in the development of
      neural tube, axial skeletons, left-right body axis, and in maintaining
      pluripotency of ES cells. Here we characterized cis-regulatory elements required
      for Zic3 expression. Enhancer activities of human-chicken-conserved noncoding
      sequences around Zic1 and Zic3 were screened using chick whole-embryo
      electroporation. We identified enhancers for meso-ectodermal tissues. Among them,
      a mesodermal enhancer (Zic3-ME) in distant 3' flanking showed robust enhancement
      of reporter gene expression in the mesodermal tissue of chicken and mouse
      embryos, and was required for mesodermal Zic3 expression in mice. Zic3-ME minimal
      core region is included in the DNase hypersensitive region of ES cells, mesoderm,
      and neural progenitors, and was bound by T (Brachyury), Eomes, Lef1, Nanog, Oct4,
      and Zic2. Zic3-ME is derived from an ancestral sequence shared with a sequence
      encoding a mitochondrial enzyme. These results indicate that Zic3-ME is an
      integrated cis-regulatory element essential for the proper expression of Zic3 in
      vertebrates, serving as a hub for a gene regulatory network including Zic3.

PMID- 30297840
TI  - A global strategy to mitigate the environmental impact of China's ruminant
      consumption boom.
AB  - Rising demand for ruminant meat and dairy products in developing countries is
      expected to double anthropogenic greenhouse gas and ammonia emissions from
      livestock by 2050. Mitigation strategies are urgently needed to meet demand while
      minimizing environmental impacts. Here, we develop scenarios for mitigating
      emissions under local vs global supply policies using data from 308 livestock
      farms across mainland China, where emissions intensities are ~50% higher than
      those in developed nations. Intensification of domestic production and globalized
      expansion through increased trade result in reductions in global emissions by
      nearly 30% over a business-as-usual scenario, but at the expense of trading
      partners absorbing the associated negative externalities of environmental
      degradation. Only adoption of a mixed strategy combining global best-practice in
      sustainable intensification of domestic production, with increased green-source
      trading as a short-term coping strategy, can meet 2050 demand while minimizing
      the local and global environmental footprint of China's ruminant consumption
      boom.

PMID- 30297841
TI  - Tuneable poration: host defense peptides as sequence probes for antimicrobial
      mechanisms.
AB  - The spread of antimicrobial resistance stimulates discovery strategies that place
      emphasis on mechanisms circumventing the drawbacks of traditional antibiotics and
      on agents that hit multiple targets. Host defense peptides (HDPs) are promising
      candidates in this regard. Here we demonstrate that a given HDP sequence
      intrinsically encodes for tuneable mechanisms of membrane disruption. Using an
      archetypal HDP (cecropin B) we show that subtle structural alterations convert
      antimicrobial mechanisms from native carpet-like scenarios to poration and non
      porating membrane exfoliation. Such distinct mechanisms, studied using low- and
      high-resolution spectroscopy, nanoscale imaging and molecular dynamics
      simulations, all maintain strong antimicrobial effects, albeit with diminished
      activity against pathogens resistant to HDPs. The strategy offers an effective
      search paradigm for the sequence probing of discrete antimicrobial mechanisms
      within a single HDP.

PMID- 30297842
TI  - ATR/Chk1 signaling induces autophagy through sumoylated RhoB-mediated lysosomal
      translocation of TSC2 after DNA damage.
AB  - DNA damage can induce autophagy; however, the underlying mechanism remains
      largely unknown. Here we report that DNA damage leads to autophagy through
      ATR/Chk1/RhoB-mediated lysosomal recruitment of TSC complex and subsequent mTORC1
      inhibition. DNA damage caused by ultraviolet light (UV) or alkylating agent
      methyl methanesulphonate (MMS) results in phosphorylation of small GTPase RhoB by
      Chk1. Phosphorylation of RhoB enhances its interaction with the TSC2, and
      promotes its sumoylation by PIAS1, which is required for RhoB/TSC complex to
      translocate to lysosomes. As a result, mTORC1 is inhibited, and autophagy is
      activated. Knockout of RhoB severely attenuates lysosomal translocation of TSC
      complex and the DNA damage-induced autophagy. Reintroducing wild-type but not
      sumoylation-resistant RhoB into RhoB-/- cells restores the onset of autophagy.
      Hence, our study identifies a molecular mechanism for translocation of TSC
      complex to lysosomes in response to DNA damage, which depends on ATR/Chk1
      mediated RhoB phosphorylation and sumoylation.

PMID- 30297843
TI  - Solution processes for ultrabroadband and omnidirectional graded-index glass
      lenses with near-zero reflectivity in high concentration photovoltaics.
AB  - Concentrator photovoltaic (CPV) systems, where incident direct solar radiation is
      tightly concentrated onto high-efficiency multi-junction solar cells by geometric
      optical elements, exhibit the highest efficiencies in converting the sun's energy
      into electric power. Their energy conversion efficiencies are greatly limited,
      however, due to Fresnel reflection losses occurring at three air/optics
      interfaces in the most sophisticated dual-stage CPV platforms. This paper
      describes a facile one-step wet-etching process to create a nanoporous surface
      with a graded-index profile on both flat and curved glasses, with capabilities of
      achieving ~99% average transmission efficiency in a wide wavelength range from
      380 nm to 1.3 um and for a wide range of incident angles up to +/-40 degrees 
      regardless of the polarization state of incident sunlight. The simplicity of the
      etching process remarkably increases their versatility in various optical
      elements that require unconventional form factors such as Fresnel lenses and
      microlens arrays, and/or demanding curvatures along with much reduced dimensions
      such as ball lenses. Etched glass surfaces on two-stage optical concentrating
      systems yield enhancements in total optical transmission efficiencies by 13.8%
      and in the photocurrent by 14.3%, as experimentally determined by measurements on
      microscale triple-junction solar cells. The presented strategy can be widely
      adapted in a variety of applications such as image sensors, display systems, and
      other optoelectronic devices.

PMID- 30297844
TI  - Direct protein-lipid interactions shape the conformational landscape of secondary
      transporters.
AB  - Secondary transporters undergo structural rearrangements to catalyze substrate
      translocation across the cell membrane - yet how such conformational changes
      happen within a lipid environment remains poorly understood. Here, we combine
      hydrogen-deuterium exchange mass spectrometry (HDX-MS) with molecular dynamics
      (MD) simulations to understand how lipids regulate the conformational dynamics of
      secondary transporters at the molecular level. Using the homologous transporters
      XylE, LacY and GlpT from Escherichia coli as model systems, we discover that
      conserved networks of charged residues act as molecular switches that drive the
      conformational transition between different states. We reveal that these
      molecular switches are regulated by interactions with surrounding phospholipids
      and show that phosphatidylethanolamine interferes with the formation of the
      conserved networks and favors an inward-facing state. Overall, this work provides
      insights into the importance of lipids in shaping the conformational landscape of
      an important class of transporters.

PMID- 30297845
TI  - Enhanced validation of antibodies for research applications.
AB  - There is a need for standardized validation methods for antibody specificity and
      selectivity. Recently, five alternative validation pillars were proposed to
      explore the specificity of research antibodies using methods with no need for
      prior knowledge about the protein target. Here, we show that these principles can
      be used in a streamlined manner for enhanced validation of research antibodies in
      Western blot applications. More than 6,000 antibodies were validated with at
      least one of these strategies involving orthogonal methods, genetic knockdown,
      recombinant expression, independent antibodies, and capture mass spectrometry
      analysis. The results show a path forward for efforts to validate antibodies in
      an application-specific manner suitable for both providers and users.

PMID- 30297848
TI  - The Exceptional Strong Face-centered Cubic Phase and Semi-coherent Phase Boundary
      in a Eutectic Dual-phase High Entropy Alloy AlCoCrFeNi.
AB  - Second phase strengthening has been applied to high entropy alloys (HEAs) for
      optimizing mechanical properties. In this study, by conducting mechanical testing
      of a eutectic dual-phase AlCoCrFeNi HEA with homogenous distribution of body
      centered cubic (BCC) and face-centered cubic (FCC) lamellar phases inside a
      transmission electron microscope, we found that although BCC was truly the hard
      phase, decreasing the proportion of BCC phase in fact increased the strength due
      to the existence of chemically disordered semi-coherent phase boundaries, which
      acted as potent impediments to dislocation motion resulting in dense dislocation
      storage in FCC phases. Moreover, the difficulty in dislocation glide caused
      massive cross-slip, and the interaction between primary slip arrays and cross
      slip systems during deformation increased the rate of dislocation accumulation by
      forming dislocation substructures, thus making the FCC phases exceptionally
      strong. Our findings not only revealed the underlying strengthening mechanism of
      eutectic dual-phase AlCoCrFeNi HEAs, but also shed light on new ways in further
      optimizing the mechanical properties of HEAs.

PMID- 30297846
TI  - Beauvericin inhibits melanogenesis by regulating cAMP/PKA/CREB and LXR-alpha/p38
      MAPK-mediated pathways.
AB  - Melanogenesis is the process of production of melanin pigments that are
      responsible for the colors of skin, eye, and hair and provide protection from
      ultraviolet radiation. However, excessive levels of melanin formation cause
      hyperpigmentation disorders such as freckles, melasma, and age spots. Liver X
      receptors (LXR) are nuclear oxysterol receptors belonging to the family of ligand
      activated transcription factors and physiological regulators of lipid and
      cholesterol metabolism. In the skin, activation of LXRs stimulates
      differentiation of keratinocytes and augments lipid synthesis in sebocytes.
      However, the function of LXRs in melanogenesis has not been clearly elucidated.
      In addition, although beauvericin, a well-known mycotoxin primarily isolated from
      several fungi, has various biological properties, its involvement in
      melanogenesis has not been reported. Therefore, in this study, we examined the
      effects of beauvericin on melanogenesis and its molecular mechanisms. Beauvericin
      decreased melanin content and tyrosinase activity without any cytotoxicity.
      Beauvericin also reduced protein levels of MITF, tyrosinase, TRP1, and TRP2. In
      addition, beauvericin suppressed cAMP-PKA-CREB signaling and upregulated
      expression of LXR-alpha, resulting in the suppression of p38 MAPK. Our results
      indicate that beauvericin attenuates melanogenesis by regulating both
      cAMP/PKA/CREB and LXR-alpha/p38 MAPK pathways, consequently leading to a
      reduction of melanin levels.

PMID- 30297849
TI  - Genome-scale fitness profile of Caulobacter crescentus grown in natural
      freshwater.
AB  - Bacterial genomes evolve in complex ecosystems and are best understood in this
      natural context, but replicating such conditions in the lab is challenging. We
      used transposon sequencing to define the fitness consequences of gene disruption
      in the bacterium Caulobacter crescentus grown in natural freshwater, compared
      with axenic growth in common laboratory media. Gene disruptions in amino-acid and
      nucleotide sugar biosynthesis pathways and in metabolic substrate transport
      machinery impaired fitness in both lake water and defined minimal medium relative
      to complex peptone broth. Fitness in lake water was enhanced by insertions in
      genes required for flagellum biosynthesis and reduced by insertions in genes
      involved in biosynthesis of the holdfast surface adhesin. We further uncovered
      numerous hypothetical and uncharacterized genes for which disruption impaired
      fitness in lake water, defined minimal medium, or both. At the genome scale, the
      fitness profile of mutants cultivated in lake water was more similar to that in
      complex peptone broth than in defined minimal medium. Microfiltration of lake
      water did not significantly affect the terminal cell density or the fitness
      profile of the transposon mutant pool, suggesting that Caulobacter does not
      strongly interact with other microbes in this ecosystem on the measured
      timescale. Fitness of select mutants with defects in cell surface biosynthesis
      and environmental sensing were significantly more variable across days in lake
      water than in defined medium, presumably owing to day-to-day heterogeneity in the
      lake environment. This study reveals genetic interactions between Caulobacter and
      a natural freshwater environment, and provides a new avenue to study gene
      function in complex ecosystems.

PMID- 30297850
TI  - CRISPR mutagenesis screening of mice.

PMID- 30297847
TI  - Functionalization of gold-nanoparticles by the Clostridium perfringens
      enterotoxin C-terminus for tumor cell ablation using the gold nanoparticle
      mediated laser perforation technique.
AB  - A recombinant produced C-terminus of the C. perfringens enterotoxin (C-CPE) was
      conjugated to gold nanoparticles (AuNPs) to produce a C-CPE-AuNP complex (C-CPE
      AuNP). By binding to claudins, the C- CPE should allow to target the AuNPs onto
      the claudin expressing tumor cells for a subsequent cell killing by application
      of the gold nanoparticle-mediated laser perforation (GNOME-LP) technique. Using
      qPCR and immunocytochemistry, we identified the human Caco-2, MCF-7 and OE-33 as
      well as the canine TiHoDMglCarc1305 as tumor cells expressing claudin-3, -4 and 
      7. Transepithelial electrical resistance (TEER) measurements of Caco-2 cell
      monolayer showed that the recombinant C-CPE bound to the claudins. GNOME-LP at a
      laser fluence of 60 mJ/cm2 and a scanning speed of 0.5 cm/s specifically
      eliminated more than 75% of claudin expressing human and canine cells treated
      with C-CPE-AuNP. The same laser fluence did not affect the cells when non
      functionalized AuNPs were used. Furthermore, most of the claudin non-expressing
      cells treated with C-CPE-AuNP were not killed by GNOME-LP. Additionally,
      application of C-CPE-AuNP to spheroids formed by MCF-7 and OE-33 cells grown in
      Matrigel reduced spheroid area. The results demonstrate that specific ablation of
      claudin expressing tumor cells is efficiently increased by activated C-CPE
      functionalized AuNPs using optical methods.

PMID- 30297852
TI  - Marine Carbonates in the Mantle Source of Oceanic Basalts: Pb Isotopic
      Constraints.
AB  - For almost fifty years, geochemists have been interpreting the clues from Pb
      isotopic ratios concerning mantle composition and evolution separately. The Pb
      isotopes of ocean island basalts (OIB) indicate that their mantle source is
      heterogeneous, most likely due to the presence of end-components derived from
      recycled crust and sediment. Some OIB have unusually high 206Pb/204Pb coming from
      one of the end-components with a long time-integrated high 238U/204Pb or MU
      (HIMU). Most OIB and many mid-ocean ridge basalts (MORB) also have high
      206Pb/204Pb, indicating a HIMU-like source. Moreover, measured 232Th/238U (kappa)
      for most MORB are lower than those deduced from their 208Pb/204Pb and
      206Pb/204Pb. Such high MU and low kappa features of oceanic basalts are
      inconsistent with the known geochemical behavior of U, Pb and Th and temporal
      evolution of the mantle; these have been respectively termed the 1st and 2nd Pb
      paradox. Here we show that subducted marine carbonates can be a source for HIMU
      and a solution to the Pb paradoxes. The results are consistent with the
      predictions of the marine carbonate recycling hypothesis that posits the Pb
      isotopes of oceanic basalts indicate a common origin and/or magma generation
      process.

PMID- 30297851
TI  - Sparsened neuronal activity in an optogenetically activated olfactory glomerulus.
AB  - Glomeruli are the functional units of olfactory information processing but little
      remains known about their individual unit function. This is due to their
      widespread activation by odor stimuli. We expressed channelrhodopsin-2 in a
      single olfactory sensory neuron type, and used laser stimulation and simultaneous
      in vivo calcium imaging to study the responses of a single glomerulus to
      optogenetic stimulation. Calcium signals in the neuropil of this glomerulus were
      representative of the sensory input and nearly identical if evoked by intensity
      matched odor and laser stimuli. However, significantly fewer glomerular layer
      interneurons and olfactory bulb output neurons (mitral cells) responded to
      optogenetic versus odor stimuli, resulting in a small and spatially compact
      optogenetic glomerular unit response. Temporal features of laser stimuli were
      represented with high fidelity in the neuropil of the glomerulus and the mitral
      cells, but not in interneurons. Increases in laser stimulus intensity were
      encoded by larger signal amplitudes in all compartments of the glomerulus, and by
      the recruitment of additional interneurons and mitral cells. No spatial expansion
      of the glomerular unit response was observed in response to stronger input
      stimuli. Our data are among the first descriptions of input-output
      transformations in a selectively activated olfactory glomerulus.

PMID- 30297854
TI  - Berry phase theory of planar Hall effect in topological insulators.
AB  - The appearance of negative longitudinal magnetoresistance (LMR) in topological
      semimetals such as Weyl and Dirac semimetals is understood as an effect of chiral
      anomaly, whereas such an anomaly is not well-defined in topological insulators.
      Nevertheless, it has been shown recently in both theory and experiments that
      nontrivial Berry phase effects can give rise to negative LMR in topological
      insulators even in the absence of chiral anomaly. In this paper, we present a
      quasi-classical theory of another intriguing phenomenon in topological insulators
      - also ascribed to chiral anomaly in Weyl and Dirac semimetals- the so-called
      planar Hall effect (PHE). PHE implies the appearance of a transverse voltage in
      the plane of applied non-parallel electric and magnetic fields, in a
      configuration in which the conventional Hall effect vanishes. Starting from
      Boltzmann transport equations we derive the expressions for PHE and LMR in
      topological insulators in the bulk conduction limit, and show the important role
      played by orbital magnetic moment. Our theoretical results for magnetoconductance
      with non-parallel electric and magnetic fields predict detailed experimental
      signatures in topological insulators - specifically of planar Hall effect - that
      can be observed in experiments.

PMID- 30297853
TI  - A Natural Deep Eutectic Solvent Formulated to Stabilize beta-Lactam Antibiotics.
AB  - beta-lactam antibiotics, such as penicillin share a very unstable chemical
      structure. In water-based solutions, such as those used for clinical
      applications, the beta-lactam ring is readily opened due to a nucleophilic or
      electrophilic attack, leading to the loss of antimicrobial activity. Since the
      achievement and maintenance of optimum therapeutic levels of beta-lactam
      antibiotics is critical for the resolution of many infectious clinical
      situations, and to avoid antibiotic resistance generation, the design of new non
      aqueous dosage forms is urgent. Recently, natural deep eutectic solvents (NADES)
      have emerged as alternative non-toxic and non-aqueous solvents for different
      biomedical applications. In this work, we formulated and characterized a NADES
      composed by betaine and urea (BU). Using this solvent, we evaluated the stability
      of clavulanic acid (CLV) and imipenem (IMP) and characterized their antimicrobial
      activities calculating the minimal inhibitory concentration. Characterization of
      BU solvent by infrared spectroscopy (IR) and nuclear magnetic resonance
      spectroscopy (NMR) indicated that the obtained solvent has a microstructure
      mainly based on hydrogen bonding interactions and water addition strongly affects
      its dynamic. The stability of beta-lactam antibiotic IMP and CLV using this
      solvent was increased by 7 fold and 2.5 fold respectively compared to water when
      analysed seven days after being dissolved. Microbiological assays showed that
      antibacterial activity at day seven was significantly decreased for both CLV and
      IMP when dissolved in water, while no change in their antibacterial properties
      was observed when antibiotics were dissolved in BU. The increased stability of
      IMP and CLV in BU may be related to the inert behaviour of the solvent and the
      higher dynamic restriction that helps antibiotics to maintain a more stable
      conformation. These data suggest the potential use of BU as a solvent to prevent
      degradation of beta-lactam antibiotics.

PMID- 30297855
TI  - Hydrophobic alkyl chains substituted to the 8-position of cyclic nucleotides
      enhance activation of CNG and HCN channels by an intricate enthalpy - entropy
      compensation.
AB  - Cyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide
      gated (HCN) channels are tetrameric non-specific cation channels in the plasma
      membrane that are activated by either cAMP or cGMP binding to specific binding
      domains incorporated in each subunit. Typical apparent affinities of these
      channels for these cyclic nucleotides range from several hundred nanomolar to
      tens of micromolar. Here we synthesized and characterized novel cAMP and cGMP
      derivatives by substituting either hydrophobic alkyl chains or similar-sized more
      hydrophilic heteroalkyl chains to the 8-position of the purine ring with the aim
      to obtain full agonists of higher potency. The compounds were tested in
      homotetrameric CNGA2, heterotetrameric CNGA2:CNGA4:CNGB1b and homotetrameric HCN2
      channels. We show that nearly all compounds are full agonists and that longer
      alkyl chains systematically increase the apparent affinity, at the best more than
      30 times. The effects are stronger in CNG than HCN2 channels which, however, are
      constitutively more sensitive to cAMP. Kinetic analyses reveal that the off-rate
      is significantly slowed by the hydrophobic alkyl chains. Molecular dynamics
      simulations and free energy calculations suggest that an intricate enthalpy -
      entropy compensation underlies the higher apparent affinity of the derivatives
      with the longer alkyl chains, which is shown to result from a reduced loss of
      configurational entropy upon binding.

PMID- 30297857
TI  - Illustrating the effect of viscoelastic additives on cavitation and turbulence
      with X-ray imaging.
AB  - The effect of viscoelastic additives on the topology and dynamics of the two
      phase flow arising within an axisymmetric orifice with a flow path constriction
      along its main axis has been investigated employing high-flux synchrotron
      radiation. X-ray Phase Contrast Imaging (XPCI) has been conducted to visualise
      the cavitating flow of different types of diesel fuel within the orifice. An
      additised blend containing Quaternary Ammonium Salt (QAS) additives with a
      concentration of 500 ppm has been comparatively examined against a pure (base)
      diesel compound. A high-flux, 12 keV X-ray beam has been utilised to obtain time
      resolved radiographs depicting the vapour extent within the orifice from two
      views (side and top) with reference to its main axis. Different test cases have
      been examined for both fuel types and for a range of flow conditions
      characterised by Reynolds number of 35500 and cavitation numbers (CN) lying in
      the range 3.0-7.7. It has been established that the behaviour of viscoelastic
      micelles in the regions of shear flow is not consistent depending on the
      cavitation regimes encountered. Namely, viscoelastic effects enhance vortical
      (string) cavitation, whereas hinder cloud cavitation. Furthermore, the use of
      additised fuel has been demonstrated to suppress the level of turbulence within
      the orifice.

PMID- 30297856
TI  - Identification of a Novel OX40L+ Dendritic Cell Subset That Selectively Expands
      Regulatory T cells.
AB  - We have previously shown GM-CSF derived bone-marrow dendritic cells (G-BMDCs) can
      induce the selective expansion of Tregs through the surface-bound molecule OX40L;
      however, the physiological role of this ex vivo derived DC subset remained to be
      elucidated. We determined GM-CSF administration to mice induced the generation of
      in vivo derived OX40L+ DCs, phenotypically similar to ex vivo OX40L+G-BMDCs, in
      the spleen, brachial lymph nodes and liver. The generation of OX40L+ DCs
      correlated with increased percentages of functionally suppressive Tregs in the
      spleen, brachial lymph nodes, and liver of GM-CSF treated mice. DCs from GM-CSF
      treated mice expanded Tregs in CD4+ T-cell co-cultures in an OX40L dependent
      manner, suggesting OX40L+ DCs may play a role in peripheral Treg homeostasis.
      Furthermore, comparing the transcriptome data of OX40L+ DCs to that of all immune
      cell types revealed OX40L+ DCs to be distinct from steady-state immune cells and,
      microarray analysis of OX40L+G-BMDCs and OX40L-G-BMDCs revealed higher expression
      of molecules that are associated with tolerogenic phenotype and could play
      important roles in the function of OX40L+ DCs. These findings suggest that OX40L+
      DCs may represent a unique DC subset induced under inflammatory conditions that
      may play an essential role in maintaining Treg homeostasis.

PMID- 30297858
TI  - Metabolic abnormalities in adult T-cell leukemia/lymphoma and induction of
      specific leukemic cell death using photodynamic therapy.
AB  - Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasm caused by
      human T-cell leukemia virus type I (HTLV-I). Therapeutic interventions have not
      been associated with satisfactory outcomes. We showed that the porphyrin
      metabolic pathway preferentially accumulates the endogenous photosensitive
      metabolite, protoporphyrin IX (PpIX) in ATL, after a short-term culture with 5
      aminolevulinic acid (ALA). PpIX accumulated 10-100-fold more in ATL leukemic
      cells when compared to healthy peripheral blood mononuclear cells (PBMCs).
      Patient specimens showed dynamic changes in flow cytometry profiles during the
      onset and progression of ATL. Furthermore, 98.7% of ATL leukemic cell death in
      the ATL patient specimens could be induced with 10 min of visible light exposure,
      while 77.5% of normal PBMCs survived. Metabolomics analyses revealed that a
      specific stage of the metabolic pathway progressively deteriorated with HTLV-I
      infection and at the onset of ATL. Therefore, this method will be useful in
      diagnosing and identifying high-risk HTLV-I carriers with single cell
      resolutions. Photodynamic therapy in the circulatory system may be a potential
      treatment due to its highly-specific, non-invasive, safe, simultaneous, and
      repeatedly-treatable modalities.

PMID- 30297860
TI  - Increasing the distance between two monomers of topoisomerase IIbeta under the
      action of antitumor agent 4beta-sulfur-(benzimidazole) 4'
      demethylepipodophyllotoxin.
AB  - Topoisomerases II (Top2s) are a group of essential enzymes involved in
      replication, transcription, chromosome condensation, and segregation via altering
      DNA topology. The mechanism of the Top2s poisons such as etoposide (VP-16) was
      reported as stabilizing the Top2-DNA complex and engendering permanent DNA
      breakage. As the structurally similar compound of VP-16, a novel 4beta-sulfur
      substituted 4'-demethylepipodophyllotoxin (DMEP) derivative (compound C-Bi) with
      superior antitumor activity was developed in our previous study. To understand
      the structural basis of the compound action, the crystal structure (2.54 A) of
      human Top2 beta-isoform (hTop2beta) cleavage complexes stabilized by compound C
      Bi was determined. However, compound C-Bi was not visible in the crystal
      structure. Through the comparison of the structures of hTop2beta-DNA-etoposide
      ternary complex and hTop2beta-DNA binary complex, it could be observed that the
      distance between drug-binding sites Arg503 of the two monomers was 26.62 A in
      hTop2beta-DNA-etoposide ternary complex and 34.54 A in hTop2beta-DNA binary
      complex, respectively. Significant twist were observed in the DNA chains of
      binary complex. It suggested that compound C-Bi played antitumor roles through
      increasing spacing of hTop2beta monomers. The changes in hTop2beta structure
      further caused double changes in the torsional direction and migration distance
      of the DNA chains, resulting in impeding religation of DNA.

PMID- 30297859
TI  - Increased levels of circulating MMP3 correlate with severe rejection in face
      transplantation.
AB  - Face transplantation is a viable treatment option for carefully selected patients
      with devastating injuries to the face. However, acute rejection episodes occur in
      more than 80% of recipients in the first postoperative year. Unfortunately,
      neither a correlation between histological grades of rejection and anti-rejection
      treatment nor systemic surrogate markers of rejection in face transplantation are
      established in clinical routine. Therefore, we utilized next generation aptamer
      based SOMAscan proteomics platform for non-invasive rejection biomarker
      discovery. Longitudinal serum samples from face transplant recipients with long
      term follow-up were included in this study. From the 1,310 proteins analyzed by
      SOMAscan, a 5-protein signature (MMP3, ACY1, IL1R2, SERPINA4, CPB2) was able to
      discriminate severe rejection from both no-rejection and nonsevere rejection
      samples. Technical validation on ELISA platform showed high correlation with the
      SOMAscan data for the MMP3 protein (rs = 0.99). Additionally, MMP3 levels were
      significantly increased during severe rejection as compared to no-rejection (p =
      0.0009) and nonsevere rejection (p = 0.0173) episodes. Pathway analyses revealed
      significant activation of the metallopeptidase activity during severe face
      transplant rejection. This pilot study demonstrates the feasibility of SOMAscan
      to identify non-invasive candidate biomarkers of rejection in face
      transplantation. Further validation in a larger independent patient cohort is
      needed.

PMID- 30297861
TI  - Separating sexual dimorphism from other morphological variation in a specimen
      complex of fossil marine reptiles (Reptilia, Ichthyosauriformes, Chaohusaurus).
AB  - The Early Triassic Chaohu Fauna from Anhui Province, China, contains the oldest
      record of Mesozoic marine reptiles, such as Cartorhynchus and Sclerocormus. Most
      specimens from the fauna belong to the ichthyosauriform Chaohusaurus, more
      specifically resembling C. chaoxianensis. However, a wide range of morphological
      variation exists within about 40 skeletons that have been prepared, likely
      reflecting mixed signals from both sexual and taxonomic differences. We test
      whether the sexual and taxonomic signals are separable based on quantification,
      aided by the knowledge of sexual dimorphism in extant marine tetrapods. There are
      two different suites of dimorphism that divide the specimens differently from
      each other yet consistently within each suite, resulting in four morphotypes in
      combination, likely representing two sexes of two taxa. Presumed males have
      larger 'organ of prehension' sensu Darwin, specifically limbs in the present
      case, for a given body length. This sexing criterion is supported by the only
      specimen of a gravid female, which belongs to the morphotype with short limbs.
      Males also have larger skulls for the trunk length compared to females. This
      study demonstrates that sexual and taxonomic signals are separable in fossil
      reptiles, with a sufficient sample size and careful analyses.

PMID- 30297862
TI  - Comparative transcriptomic profile of tolerogenic dendritic cells differentiated
      with vitamin D3, dexamethasone and rapamycin.
AB  - Tolerogenic dendritic cell (tolDC)-based therapies have become a promising
      approach for the treatment of autoimmune diseases by their potential ability to
      restore immune tolerance in an antigen-specific manner. However, the broad
      variety of protocols used to generate tolDC in vitro and their functional and
      phenotypical heterogeneity are evidencing the need to find robust biomarkers as a
      key point towards their translation into the clinic, as well as better
      understanding the mechanisms involved in the induction of immune tolerance. With
      that aim, in this study we have compared the transcriptomic profile of tolDC
      induced with either vitamin D3 (vitD3-tolDC), dexamethasone (dexa-tolDC) or
      rapamycin (rapa-tolDC) through a microarray analysis in 5 healthy donors. The
      results evidenced that common differentially expressed genes could not be found
      for the three different tolDC protocols. However, individually, CYP24A1, MUCL1
      and MAP7 for vitD3-tolDC; CD163, CCL18, C1QB and C1QC for dexa-tolDC; and CNGA1
      and CYP7B1 for rapa-tolDC, constituted good candidate biomarkers for each
      respective cellular product. In addition, a further gene set enrichment analysis
      of the data revealed that dexa-tolDC and vitD3-tolDC share several immune
      regulatory and anti-inflammatory pathways, while rapa-tolDC seem to be playing a
      totally different role towards tolerance induction through a strong
      immunosuppression of their cellular processes.

PMID- 30297864
TI  - Generation of two-cell cloned embryos from mouse faecal cell.
AB  - Cloning animals using nuclear transfer (NT) provides the opportunity to preserve
      endangered species. However, there are risks associated with the collection of
      donor cells from a body, which may cause accidental death of the animal. Here, we
      tried to collect faeces-derived cells and examined the usability of those nuclei
      as a donor for NT. A relatively large number of cells could be collected from GFP
      Tg mouse faeces by this method. After NT, only 4.2% of the reconstructed oocytes
      formed pseudo-pronucleus. This rate increased up to 25% when GFP and Hoechst were
      used as a marker to select better cells. However, the reconstructed
      oocytes/embryos showed several abnormalities, such as shrunken nuclear membranes
      and abnormal distribution of tubulin, and none of them developed beyond one-cell
      stage embryos. These developmental failures were caused by not only toxic
      substances derived from faeces but also intrinsic DNA damage of donor cell
      nuclei. However, when the serial NT was performed, some of the cloned embryos
      could develop to the two-cell stage. This method may remove toxic substances and
      enhance DNA repair in the oocyte cytoplasm. Thus, these results indicate that
      faeces cells might be useful for the conservation of endangered species when
      technical improvements are achieved.

PMID- 30297863
TI  - Genetic and mechanistic basis for APOBEC3H alternative splicing, retrovirus
      restriction, and counteraction by HIV-1 protease.
AB  - Human APOBEC3H (A3H) is a single-stranded DNA cytosine deaminase that inhibits
      HIV-1. Seven haplotypes (I-VII) and four splice variants (SV154/182/183/200) with
      differing antiviral activities and geographic distributions have been described,
      but the genetic and mechanistic basis for variant expression and function remains
      unclear. Using a combined bioinformatic/experimental analysis, we find that SV200
      expression is specific to haplotype II, which is primarily found in sub-Saharan
      Africa. The underlying genetic mechanism for differential mRNA splicing is an
      ancient intronic deletion [del(ctc)] within A3H haplotype II sequence. We show
      that SV200 is at least fourfold more HIV-1 restrictive than other A3H splice
      variants. To counteract this elevated antiviral activity, HIV-1 protease cleaves
      SV200 into a shorter, less restrictive isoform. Our analyses indicate that, in
      addition to Vif-mediated degradation, HIV-1 may use protease as a  counter
      defense mechanism against A3H in >80% of sub-Saharan African populations.

PMID- 30297866
TI  - Right ventricular congestion in preterm neonates with chronic pulmonary
      hypertension.

PMID- 30297865
TI  - Identification of pharmacological inhibitors of conventional protein secretion.
AB  - The retention using selective hooks (RUSH) system allows to withhold a
      fluorescent biosensor such as green fluorescent protein (GFP) fused to a
      streptavidin-binding peptide (SBP) by an excess of streptavidin molecules that
      are addressed to different subcellular localizations. Addition of biotin
      competitively disrupts this interaction, liberating the biosensor from its hook.
      We constructed a human cell line co-expressing soluble secretory-SBP-GFP (ss-SBP
      GFP) and streptavidin within the endoplasmic reticulum (ER) lumen and then used
      this system to screen a compound library for inhibitors of the biotin-induced
      release of ss-SBP-GFP via the conventional Golgi-dependent protein secretion
      pathway into the culture supernatant. We identified and validated a series of
      molecularly unrelated drugs including antianginal, antidepressant, anthelmintic,
      antipsychotic, antiprotozoal and immunosuppressive agents that inhibit protein
      secretion. These compounds vary in their capacity to suppress protein synthesis
      and to compromise ER morphology and Golgi integrity, as well as in the degree of
      reversibility of such effects. In sum, we demonstrate the feasibility and utility
      of a novel RUSH-based phenotypic screening assay.

PMID- 30297867
TI  - ALPK1: innate attraction to the sweetness of bacteria.

PMID- 30297868
TI  - Pyruvate kinase M2 regulates homologous recombination-mediated DNA double-strand
      break repair.
AB  - Resistance to genotoxic therapies is a primary cause of treatment failure and
      tumor recurrence. The underlying mechanisms that activate the DNA damage response
      (DDR) and allow cancer cells to escape the lethal effects of genotoxic therapies
      remain unclear. Here, we uncover an unexpected mechanism through which pyruvate
      kinase M2 (PKM2), the highly expressed PK isoform in cancer cells and a master
      regulator of cancer metabolic reprogramming, integrates with the DDR to directly
      promote DNA double-strand break (DSB) repair. In response to ionizing radiation
      and oxidative stress, ATM phosphorylates PKM2 at T328 resulting in its nuclear
      accumulation. pT328-PKM2 is required and sufficient to promote homologous
      recombination (HR)-mediated DNA DSB repair through phosphorylation of CtBP
      interacting protein (CtIP) on T126 to increase CtIP's recruitment at DSBs and
      resection of DNA ends. Disruption of the ATM-PKM2-CtIP axis sensitizes cancer
      cells to a variety of DNA-damaging agents and PARP1 inhibition. Furthermore,
      increased nuclear pT328-PKM2 level is associated with significantly worse
      survival in glioblastoma patients. Combined, these data advocate the use of PKM2
      targeting strategies as a means to not only disrupt cancer metabolism but also
      inhibit an important mechanism of resistance to genotoxic therapies.

PMID- 30297869
TI  - Elimination of CD4lowHLA-G+ T cells overcomes castration-resistance in prostate
      cancer therapy.
AB  - Androgen deprivation therapy (ADT) is a main treatment for prostate cancer (PCa)
      but the disease often recurs and becomes castration-resistant in nearly all
      patients. Recent data implicate the involvement of immune cells in the
      development of this castration-resistant prostate cancer (CRPC). In particular, T
      cells have been found to be expanded in both PCa patients and mouse models
      shortly after androgen deprivation. However, whether or which of the T cell
      subtypes play an important role during the development of CRPC is unknown. Here
      we identified a novel population of CD4lowHLA-G+ T cells that undergo significant
      expansion in PCa patients after ADT. In mouse PCa models, a similar CD4low T cell
      population expands during the early stages of CRPC onset. These cells are
      identified as IL-4-expressing TH17 cells, and are shown to be associated with
      CRPC onset in patients and essential for the development of CRPC in mouse models.
      Mechanistically, CD4lowHLA-G+ T cells drive androgen-independent growth of
      prostate cancer cells by modulating the activity and migration of CD11blowF4/80hi
      macrophages. Furthermore, following androgen deprivation, elevated PGE2-EP2
      signaling inhibited the expression of CD4 in thymocytes, and subsequently induced
      the polarization of CD4low naive T cells towards the IL-4-expressing TH17
      phenotype via up-regulation of IL23R. Therapeutically, inactivating PGE2
      signaling with celecoxib at a time when CD4lowHLA-G+ T cells appeared, but not
      immediately following androgen deprivation, dramatically suppressed the onset of
      CRPC. Collectively, our results indicate that an unusual population of CD4lowHLA
      G+ T cells is essential for the development of CRPC and point to a new
      therapeutic avenue of combining ADT with PGE2 inhibition for the treatment of
      prostate cancer.

PMID- 30297870
TI  - METTL3-mediated N6-methyladenosine mRNA modification enhances long-term memory
      consolidation.
AB  - The formation of long-term memory is critical for learning ability and social
      behaviors of humans and animals, yet its underlying mechanisms are largely
      unknown. We found that the efficacy of hippocampus-dependent memory consolidation
      is regulated by METTL3, an RNA N6-methyladenosine (m6A) methyltransferase,
      through promoting the translation of neuronal early-response genes. Such effect
      is exquisitely dependent on the m6A methyltransferase function of METTL3.
      Depleting METTL3 in mouse hippocampus reduces memory consolidation ability, yet
      unimpaired learning outcomes can be achieved if adequate training was given or
      the m6A methyltransferase function of METTL3 was restored. The abundance of
      METTL3 in wild-type mouse hippocampus is positively correlated with learning
      efficacy, and overexpression of METTL3 significantly enhances long-term memory
      consolidation. These findings uncover a direct role of RNA m6A modification in
      regulating long-term memory formation, and also indicate that memory efficacy
      difference among individuals could be compensated by repeated learning.

PMID- 30297873
TI  - Author Correction: Microbial niches in marine oxygen minimum zones.
AB  - In Figure  3, 'Candidatus Scalindua' and Thaumarchaeota were erroneously shown to
      produce nitrous oxide (N2O). As neither group directly produces N2O, the arrows
      and products have been removed both online and in the pdf. The authors apologize
      for any confusion caused.

PMID- 30297872
TI  - Temperature affects the biology of Schmidtea mediterranea.
AB  - Studies of tissue regeneration and host-pathogen interactions using the model
      planarian Schmidtea mediterranea have been performed at an experimental
      temperature of 19  degrees C. S. mediterranea planarians exposed to 19  degrees C
      32  degrees C were observed for survival, mobility, feeding and regeneration for
      three months and elimination of the Staphylococcus aureus pathogen over six days.
      S. mediterranea planarians died at 30  degrees C-32  degrees C after 18 days of
      observation but tolerated temperatures of 19  degrees C up to 28  degrees C with
      non-significant differences in mobility and feeding behavior. Genetic
      malleability tested by RNAi feeding was still efficient at 26  degrees C and 28 
      degrees C. Concerning the immune capacity of planarians, we reported an
      exacerbation of the immune response in worms infected by S. aureus at 26  degrees
      C and 28  degrees C. These observations suggest a temperature modulation of
      planarian stem cells and illustrate the importance of modulating experimental
      temperature when using planarians as model organisms to study regeneration and
      immune response.

PMID- 30297871
TI  - A dynamic N6-methyladenosine methylome regulates intrinsic and acquired
      resistance to tyrosine kinase inhibitors.
AB  - N6-methyladenosine (m6A) on mRNAs is critical for various biological processes,
      yet whether m6A regulates drug resistance remains unknown. Here we show that
      developing resistant phenotypes during tyrosine kinase inhibitor (TKI) therapy
      depends on m6A reduction resulting from FTO overexpression in leukemia cells.
      This deregulated FTO-m6A axis pre-exists in naive cell populations that are
      genetically homogeneous and is inducible/reversible in response to TKI treatment.
      Cells with mRNA m6A hypomethylation and FTO upregulation demonstrate more TKI
      tolerance and higher growth rates in mice. Either genetic or pharmacological
      restoration of m6A methylation through FTO deactivation renders resistant cells
      sensitive to TKIs. Mechanistically, the FTO-dependent m6A demethylation enhances
      mRNA stability of proliferation/survival transcripts bearing m6A and subsequently
      leads to increased protein synthesis. Our findings identify a novel function for
      the m6A methylation in regulating cell fate decision and demonstrate that dynamic
      m6A methylome is an additional epigenetic driver of reversible TKI-tolerance
      state, providing a mechanistic paradigm for drug resistance in cancer.

PMID- 30297874
TI  - New tricks for an old drug.

PMID- 30297875
TI  - MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG.
AB  - alpha-Ketoglutarate (alphaKG) is a key node in many important metabolic pathways.
      The alphaKG analog N-oxalylglycine (NOG) and its cell-permeable prodrug
      dimethyloxalylglycine (DMOG) are extensively used to inhibit alphaKG-dependent
      dioxygenases. However, whether NOG interference with other alphaKG-dependent
      processes contributes to its mode of action remains poorly understood. Here we
      show that, in aqueous solutions, DMOG is rapidly hydrolyzed, yielding
      methyloxalylglycine (MOG). MOG elicits cytotoxicity in a manner that depends on
      its transport by monocarboxylate transporter 2 (MCT2) and is associated with
      decreased glutamine-derived tricarboxylic acid-cycle flux, suppressed
      mitochondrial respiration and decreased ATP production. MCT2-facilitated entry of
      MOG into cells leads to sufficiently high concentrations of NOG to inhibit
      multiple enzymes in glutamine metabolism, including glutamate dehydrogenase.
      These findings reveal that MCT2 dictates the mode of action of NOG by determining
      its intracellular concentration and have important implications for the use of
      (D)MOG in studying alphaKG-dependent signaling and metabolism.

PMID- 30297876
TI  - Lead: a hidden "untested" risk in neonatal blood transfusion.
AB  - BACKGROUND: Neonates may be exposed to lead (Pb) through blood transfusions from
      donors. Pb exposure has neurological, cardiovascular, renal, and other adverse
      effects. The study aimed to (i) determine the blood lead levels (BLLs) in
      different blood product units (whole blood, packed red blood cells (pRBCs),
      platelets, and plasma transfused to neonates) and (ii) estimate the proportion of
      units with high BLLs. METHODS: Residual blood from blood bank bags that were used
      for neonatal transfusion were collected: 25 samples from each type of blood
      product except for whole blood (10 samples). The Pb analysis was performed using
      the atomic absorption method. The study was conducted at the Suez Canal
      University Hospital, Egypt. RESULTS: The mean of BLL in pRBCs, platelets, plasma,
      and whole blood were 136, 199, 108, and 130 ug/L, respectively; 60% contained Pb
      above 50 ug/L. The highest BLLs were in platelet units. CONCLUSIONS: The present
      study showed for the first time that platelets and plasma in addition to whole
      blood and pRBCs used for neonatal transfusions are sources of Pb. Re-evaluation
      of the guidelines is mandatory for the safety of the neonates. Long-term
      neurodevelopment assessment of neonates exposed to high Pb is warranted.

PMID- 30297877
TI  - Oxygen therapy of the newborn from molecular understanding to clinical practice.
AB  - Oxygen is one of the most critical components of life. Nature has taken billions
      of years to develop optimal atmospheric oxygen concentrations for human life,
      evolving from very low, peaking at 30% before reaching 20.95%. There is now
      increased understanding of the potential toxicity of both too much and too little
      oxygen, especially for preterm and asphyxiated infants and of the potential and
      lifelong impact of oxygen exposure, even for a few minutes after birth. In this
      review, we discuss the contribution of knowledge gleaned from basic science
      studies and their implication in the care and outcomes of the human infant within
      the first few minutes of life and afterwards. We emphasize current knowledge gaps
      and research that is needed to answer a problem that has taken Nature a
      considerably longer time to resolve.

PMID- 30297878
TI  - Fetal programming of neuropsychiatric disorders by maternal pregnancy depression:
      a systematic mini review.
AB  - BACKGROUND: Maternal depression complicates a large proportion of pregnancies.
      Current evidence shows numerous harmful effects on the offspring. Reviews, which
      include depression, concluded that stress has harmful effects on the offspring's
      outcomes neuro-cognitive development, temperament traits, and mental disorders.
      OBJECTIVE: This mini review of recent studies, sought to narrow the scope of
      exposure and identify studies specifically assessing prenatal depression and
      offspring neuropsychiatric outcomes. STUDY ELIGIBILITY CRITERIA: The review
      included longitudinal, cohort, cross-sectional, clinical, quasi-experimental,
      epidemiological, or intervention study designs published in English from 2014 to
      2018. PARTICIPANTS: Study populations included mother-child dyads, mother-father
      child triads, mother-alternative caregiver-child triads, and family studies
      utilizing sibling comparisons. METHODS: We searched PubMED and Web of Science.
      Study inclusion and data extraction were based on standardized templates. The
      quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS:
      Thirteen studies examining neuropsychiatric outcomes were included. We judged the
      evidence to be moderate to high quality. CONCLUSIONS: Our review supports that
      maternal prenatal depression is associated with neuropsychiatric adversities in
      children. IMPLICATIONS: Future investigations should unravel the biological
      underpinnings and target timely interventions as early in pregnancy as possible
      to prevent offspring neuropsychiatric harms.

PMID- 30297879
TI  - Erythropoietin serum levels, versus anaemia as risk factors for severe
      retinopathy of prematurity.
AB  - BACKGROUND: Preterm infants with anaemia are treated with recombinant human
      erythropoietin (rhEPO). It is debated whether rhEPO treatment is a risk factor
      for retinopathy of prematurity (ROP). We evaluated longitudinal EPO and
      haemoglobin levels, blood transfusions and neonatal morbidities as risk factors
      for severe ROP. METHOD: This prospective study included 78 Swedish infants, born
      <28 weeks gestational age (GA), screened for ROP. We tested serum EPO levels on
      postnatal days 1, 7, 14 and 28 and at postmenstrual ages 32, 36 and 40 weeks.
      Haemoglobin levels and blood transfusions were recorded during postnatal weeks 1
      4. Anaemia was defined as haemoglobin <=110 g/L. RESULTS: During postnatal week
      1, infants with severe ROP requiring treatment (28%) more frequently developed
      anaemia (42.9% versus 8.0%, P = 0.003) and had higher mean EPO levels (postnatal
      day 7: 14.2 versus 10.8 mIU/mL, P = 0.003) compared to infants with no or less
      severe ROP not requiring treatment. In multivariable analyses, GA and anaemia
      during week 1 remained significant risk factors, but elevated EPO level postnatal
      day 7 was no longer significant. CONCLUSIONS: Among infants born <28 weeks GA,
      anaemia during week 1 was a significant risk factor for severe ROP requiring
      treatment but not elevated EPO levels.

PMID- 30297880
TI  - Metabolomic profiles and development of metabolic risk during the pubertal
      transition: a prospective study in the ELEMENT Project.
AB  - OBJECTIVES: (1) Examine associations of a branched-chain amino acid (BCAA)
      metabolite pattern with metabolic risk across adolescence; (2) use Least Absolute
      Shrinkage and Selection Operator (LASSO) to identify novel metabolites of
      metabolic risk. METHODS: We used linear regression to examine associations of a
      BCAA score with change (?) in metabolic biomarkers over 5-year follow-up in 179
      adolescents 8-14 years at baseline. Next, we applied LASSO, a regularized
      regression technique well suited for reduction of high-dimensional data, to
      identify metabolite predictors of ?biomarkers. RESULTS: In boys, the BCAA score
      corresponded with decreasing C-peptide, C-peptide-based insulin resistance (CP
      IR), total cholesterol (TC), and low-density-lipoprotein cholesterol (LDL). In
      pubertal girls, the BCAA pattern corresponded with increasing C-peptide and
      leptin. LASSO identified asparagine as a predictor of decreasing C-peptide (beta
      = -0.33) and CP-IR (beta = -0.012), and acetyl-carnitine (beta = 2.098), 4
      hydroxyproline (beta = -0.050), ornithine (beta = -0.353), and alpha
      aminoisobutyric acid (beta = -0.793) as determinants of TC in boys. In girls,
      histidine was a negative determinant of TC (beta = -0.033). CONCLUSIONS: The BCAA
      pattern was associated with ?glycemia and ?lipids in a sex-specific manner. LASSO
      identified asparagine, which influences growth hormone secretion, as a
      determinant of decreasing C-peptide and CP-IR in boys, and metabolites on lipid
      metabolism pathways as determinants of decreasing cholesterol in both sexes.

PMID- 30297881
TI  - Increased CD3+ T cells with a low FOXP3+/CD8+ T cell ratio can predict anti-PD-1
      therapeutic response in non-small cell lung cancer patients.
AB  - To determine whether tumor microenvironments affect the clinical response to anti
      PD-1 therapy in non-small cell lung cancer, we investigated the expression level
      of PD-L1 and tumor infiltrating lymphocytes and elucidate their predictive role.
      Thirty-eight pretreatment and two post-treatment specimens from 36 advanced,
      treatment-refractory non-small cell lung cancer patients who underwent PD-1
      blockade therapy were analyzed. PD-L1 expression by tumor cells and the
      distribution of CD3, CD8, CD4, FOXP3 and PD-1 positive tumor infiltrating
      lymphocytes were immunohistochemically assessed and counted using digital image
      analyzer. CD3+ and CD8+ T cells were distributed more in PD-L1 positive group
      compared to PD-L1 negative group. Conversely, EGFR mutant group showed fewer CD3+
      T cells than EGFR-naive group. The patients in the clinical benefit group with PD
      1 blockade showed a higher number of CD3+, CD8+ T cells and a higher CD8+/CD3+ T
      cell ratio (p = 0.003, p = 0.001, and p = 0.042) and a lower FOXP3+/CD8+ T cell
      ratio compared to non-responders (p = 0.001). In multivariate logistic regression
      analysis, increased CD3+ T cell infiltration and low FOXP3+/CD8+ T cell ratio
      were found to be independent predictors of clinical benefit with PD-1 blockade (p
      = 0.014 and p = 0.03, respectively). Using receiver operating characteristic
      curves, levels of CD3+ T cells and FOXP3+/CD8+ T cell ratio that provide the best
      distinguishing point between responder versus non-responder to PD-1 blockade were
      617.5/mm2 and 25%, respectively (p = 0.007 and p = 0.003). Considering that 1 mm2
      is about 5 high power fields (HPF), a good response to the PD-1 blockade can be
      expected when the number of CD3 T cells is observed to be 120 per HPF and when
      CD8+ T cells and FOXP3+ T cells are present at a ratio greater than 4:1. Tumor
      infiltrating lymphocytes might become a promising biomarker as an independent
      predictive factor of response to PD-1 blockade that may also guide therapeutic
      decisions.

PMID- 30297882
TI  - The clinicopathologic features of chronic active Epstein-Barr virus infective
      enteritis.
AB  - Chronic active Epstein-Barr virus infective enteritis (CAEBV enteritis) is rare
      and has not been well described yet. Therefore, we reported the clinicopathologic
      features of 11 patients with chronic active Epstein-Barr virus infective
      enteritis and their differences from inflammatory bowel disease. The major
      clinical presentations of chronic active Epstein-Barr virus infective enteritis
      were intermittent fever over 39  degrees C (100%), diarrhea (73%), abdominal pain
      (64%), lymphadenopathy (64%), splenomegaly (64%), and hepatomegaly (27%). The
      main endoscopic findings included numerous shallow, small, and irregular ulcers,
      mainly involving colon and small intestine together, no cobble-like appearance,
      and longitudinal ulcers. Compared to inflammatory bowel disease patients, the
      frequency of intermittent fever, hepatomegaly, splenomegaly, lymphadenopathy, the
      value of C-reactive protein, and serum Epstein-Barr virus DNA (EBV DNA) were
      significantly higher in chronic active Epstein-Barr virus infective enteritis
      patients (p < 0.01). The histologic findings show transmural inflammation with
      extended lymphoid infiltration, fissuring ulcers, and intraepithelial
      lymphocytosis. But chronic active Epstein-Barr virus infective enteritis lacked
      granulomas and connective tissue changes such as neural hypertrophy and thickened
      muscularis mucosae. Three chronic active Epstein-Barr virus infective enteritis
      patients died within 5 years of disease onset, and those three patients have
      received total colectomy, two of them died within 1 month after surgery. In this
      study, clinicopathologic features have been summarized to better recognize
      chronic active Epstein-Barr virus infective enteritis. There are resemblances
      between chronic active Epstein-Barr virus infective enteritis and inflammatory
      bowel disease, but some symptoms, signs, and indexes like intermittent fever,
      hepatomegaly, splenomegaly, lymphadenopathy, and elevated C-reactive protein,
      Epstein-Barr virus DNA are characteristics to differentiate chronic active
      Epstein-Barr virus infective enteritis and inflammation. Histopathological
      features also help the discrimination. Serum Epstein-Barr virus DNA and
      intestinal tissue in situ hybridization for Epstein-Barr virus-encoded RNA are
      recommended to exclude chronic active Epstein-Barr virus infective enteritis.

PMID- 30297883
TI  - Discharge Performance of Zinc-Air Flow Batteries Under the Effects of Sodium
      Dodecyl Sulfate and Pluronic F-127.
AB  - Zinc-air batteries are a promising technology for large-scale electricity
      storage. However, their practical deployment has been hindered by some issues
      related to corrosion and passivation of the zinc anode in an alkaline
      electrolyte. In this work, anionic surfactant sodium dodecyl sulfate (SDS) and
      nonionic surfactant Pluronic F-127 (P127) are examined their applicability to
      enhance the battery performances. Pristine zinc granules in 7 M KOH, pristine
      zinc granules in 0-8 mM SDS/7 M KOH, pristine zinc granules in 0-1000 ppm P127/7
      M KOH, and SDS coated zinc granules in 7 M KOH were examined. Cyclic
      voltammograms, potentiodynamic polarization, and electrochemical impedance
      spectroscopy confirmed that using 0.2 mM SDS or 100 ppm P127 effectively
      suppressed the anode corrosion and passivation. Nevertheless, direct coating SDS
      on the zinc anode showed adverse effects because the thick layer of SDS coating
      acted as a passivating film and blocked the removal of the anode oxidation
      product from the zinc surface. Furthermore, the performances of the zinc-air flow
      batteries were studied. Galvanostatic discharge results indicated that the
      improvement of discharge capacity and energy density could be sought by the
      introduction of the surfactants to the KOH electrolyte. The enhancement of
      specific discharge capacity for 30% and 24% was observed in the electrolyte
      containing 100 ppm P127 and 0.2 mM SDS, respectively.

PMID- 30297885
TI  - Extraction and liposome reconstitution of membrane proteins with their native
      lipids without the use of detergents.
AB  - Functional studies of membrane-bound channels, transporters or signal transducers
      require that the protein of interest resides in a membrane that separates two
      compartments. One approach that is commonly used to prepare these systems is to
      reconstitute the protein in liposomes. An intermediate step of this method is
      purification of the protein, which typically involves solubilization of the
      native membrane using detergent. The use of detergents often results in removal
      of lipids surrounding the protein, which may alter its structure and function.
      Here, we have employed a method for isolation of membrane proteins with a disc of
      their native lipids to develop an approach that allows transfer of the purified
      membrane protein to liposomes without the use of any detergents.

PMID- 30297884
TI  - An efficient and multiple target transgenic RNAi technique with low toxicity in
      Drosophila.
AB  - Being relatively simple and practical, Drosophila transgenic RNAi is the
      technique of top priority choice to quickly study genes with pleiotropic
      functions. However, drawbacks have emerged over time, such as high level of false
      positive and negative results. To overcome these shortcomings and increase
      efficiency, specificity and versatility, we develop a next generation transgenic
      RNAi system. With this system, the leaky expression of the basal promoter is
      significantly reduced, as well as the heterozygous ratio of transgenic RNAi
      flies. In addition, it has been first achieved to precisely and efficiently
      modulate highly expressed genes. Furthermore, we increase versatility which can
      simultaneously knock down multiple genes in one step. A case illustration is
      provided of how this system can be used to study the synthetic developmental
      effect of histone acetyltransferases. Finally, we have generated a collection of
      transgenic RNAi lines for those genes that are highly homologous to human disease
      genes.

PMID- 30297886
TI  - A comprehensive overview of genomic imprinting in breast and its deregulation in
      cancer.
AB  - Genomic imprinting plays an important role in growth and development. Loss of
      imprinting (LOI) has been found in cancer, yet systematic studies are impeded by
      data-analytical challenges. We developed a methodology to detect monoallelically
      expressed loci without requiring genotyping data, and applied it on The Cancer
      Genome Atlas (TCGA, discovery) and Genotype-Tissue expression project (GTEx,
      validation) breast tissue RNA-seq data. Here, we report the identification of 30
      putatively imprinted genes in breast. In breast cancer (TCGA), HM13 is featured
      by LOI and expression upregulation, which is linked to DNA demethylation. Other
      imprinted genes typically demonstrate lower expression in cancer, often
      associated with copy number variation and aberrant DNA methylation.
      Downregulation in cancer frequently leads to higher relative expression of the
      (imperfectly) silenced allele, yet this is not considered canonical LOI given the
      lack of (absolute) re-expression. In summary, our novel methodology highlights
      the massive deregulation of imprinting in breast cancer.

PMID- 30297888
TI  - Evaluation of ENSO simulations in CMIP5 models: A new perspective based on
      percolation phase transition in complex networks.
AB  - In this study, the performance of CMIP5 models in simulating the El Nino-Southern
      Oscillation (ENSO) is evaluated by using a new metric based on percolation
      theory. The surface air temperatures (SATs) over the tropical Pacific Ocean are
      constructed as a SAT network, and the nodes within the network are linked if they
      are highly connected (e.g., high correlations). It has been confirmed from
      reanalysis datasets that the SAT network undergoes an abrupt percolation phase
      transition when the influences of the sea surface temperature anomalies (SSTAs)
      below are strong enough. However, from simulations of the CMIP5 models, most
      models are found incapable of capturing the observed phase transition at a proper
      critical point Pc. For the 15 considered models, four even miss the phase
      transition, indicating that the simulated SAT network is too stable to be
      significantly changed by the SSTA below. Only four models can be considered
      cautiously with some skills in simulating the observed phase transition of the
      SAT network. By comparing the simulated SSTA patterns with the node
      vulnerabilities, which is the chance of each node being isolated during a ENSO
      event, we find that the improperly simulated sea-air interactions are responsible
      for the missing of the observed percolation phase transition. Accordingly, a
      careful study of the sea-air couplers, as well as the atmospheric components of
      the CMIP5 models is suggested. Since the percolation phase transition of the SAT
      network is a useful phenomenon to indicate whether the ENSO impacts can be
      transferred remotely, it deserves more attention for future model development.

PMID- 30297887
TI  - MSCs inhibit tumor progression and enhance radiosensitivity of breast cancer
      cells by down-regulating Stat3 signaling pathway.
AB  - The acquisition of radioresistance by breast cancer cells during radiotherapy may
      lead to cancer recurrence and poor survival. Signal transducer and activator of
      transcription 3 (Stat3) is activated in breast cancer cells and, therefore, may
      be an effective target for overcoming therapeutic resistance. Mesenchymal stem
      cells (MSCs) have been investigated for use in cancer treatment. Here, we
      investigated the potential of MSC conditioned medium (MSC-CM) in sensitizing
      breast cancer to radiotherapy. It was found that MSC-CM could inhibit the level
      of activated Stat3, suppress cancer growth, and exhibit synergetic effects with
      radiation treatment in vitro and in vivo. Furthermore, MSC-CM reduced the ALDH
      positive cancer stem cells (CSCs) population, modulated several potential stem
      cell markers, and decreased tumor migration, as well as metastasis. These results
      demonstrate that MSC-CM suppresses breast cancer cells growth and sensitizes
      cancer cells to radiotherapy through inhibition of the Stat3 signaling pathway,
      thus, providing a novel strategy for breast cancer therapy by overcoming
      radioresistance.

PMID- 30297890
TI  - Early immune development.

PMID- 30297891
TI  - Gene editing for Duchenne muscular dystrophy.

PMID- 30297889
TI  - Ultra-long-acting removable drug delivery system for HIV treatment and
      prevention.
AB  - Non-adherence to medication is an important health care problem, especially in
      the treatment of chronic conditions. Injectable long-acting (LA) formulations of
      antiretrovirals (ARVs) represent a viable alternative to improve adherence to
      HIV/AIDS treatment and prevention. However, the LA-ARV formulations currently in
      clinical trials cannot be removed after administration even if adverse events
      occur. Here we show an ultra-LA removable system that delivers drug for up to 9
      months and can be safely removed to stop drug delivery. We use two pre-clinical
      models for HIV transmission and treatment, non-human primates (NHP) and humanized
      BLT (bone marrow/liver/thymus) mice and show a single dose of subcutaneously
      administered ultra-LA dolutegravir effectively delivers the drug in both models
      and show suppression of viremia and protection from multiple high-dose vaginal
      HIV challenges in BLT mice. This approach represents a potentially effective
      strategy for the ultra-LA drug delivery with multiple possible therapeutic
      applications.

PMID- 30297892
TI  - Towards poliovirus eradication.

PMID- 30297893
TI  - Interpreting the unknown.

PMID- 30297894
TI  - Live bacterial therapies for metabolic disease.

PMID- 30297896
TI  - GWAS to the people.

PMID- 30297895
TI  - Beneficial effects on vision in patients undergoing retinal gene therapy for
      choroideremia.
AB  - Retinal gene therapy is increasingly recognized as a novel molecular intervention
      that has huge potential in treating common causes of blindness, the majority of
      which have a genetic aetiology1-5. Choroideremia is a chronic X-linked retinal
      degeneration that was first described in 18726. It leads to progressive blindness
      due to deficiency of Rab-escort protein 1 (REP1). We designed an adeno-associated
      viral vector to express REP1 and assessed it in a gene therapy clinical trial by
      subretinal injection in 14 patients with choroideremia. The primary endpoint was
      vision change in treated eyes 2 years after surgery compared to unoperated fellow
      eyes. Despite complications in two patients, visual acuity improved in the 14
      treated eyes over controls (median 4.5 letter gain, versus 1.5 letter loss, P =
      0.04), with 6 treated eyes gaining more than one line of vision (>5 letters). The
      results suggest that retinal gene therapy can sustain and improve visual acuity
      in a cohort of predominantly late-stage choroideremia patients in whom rapid
      visual acuity loss would ordinarily be predicted.

PMID- 30297897
TI  - Tumors evading CARs-the chase is on.

PMID- 30297898
TI  - A prescription for better opioid prescribing?

PMID- 30297900
TI  - Lost in the maze.

PMID- 30297901
TI  - Going to waste.

PMID- 30297902
TI  - Towards therapeutic base editing.

PMID- 30297899
TI  - Late-stage tumors induce anemia and immunosuppressive extramedullary erythroid
      progenitor cells.
AB  - Impaired immunity in patients with late-stage cancer is not limited to antitumor
      responses, as demonstrated by poor vaccination protection and high susceptibility
      to infection1-3. This has been largely attributed to chemotherapy-induced
      impairment of innate immunity, such as neutropenia2, whereas systemic effects of
      tumors on hematopoiesis and adoptive immunity remain incompletely understood.
      Here we observed anemia associated with severe deficiency of CD8+ T cell
      responses against pathogens in treatment-naive mice bearing large tumors.
      Specifically, we identify CD45+ erythroid progenitor cells (CD71+TER119+; EPCs)
      as robust immunosuppressors. CD45+ EPCs, induced by tumor growth-associated
      extramedullary hematopoiesis, accumulate in the spleen to become a major
      population, outnumbering regulatory T cells (Tregs) and myeloid-derived
      suppressor cells (MDSCs). The CD45+ EPC transcriptome closely resembles that of
      MDSCs, and, like MDSCs, reactive oxygen species production is a major mechanism
      underlying CD45+ EPC-mediated immunosuppression. Similarly, an immunosuppressive
      CD45+ EPC population was detected in patients with cancer who have anemia. These
      findings identify a major population of immunosuppressive cells that likely
      contributes to the impaired T cell responses commonly observed in patients with
      advanced cancer.

PMID- 30297903
TI  - In utero CRISPR-mediated therapeutic editing of metabolic genes.
AB  - In utero gene editing has the potential to prenatally treat genetic diseases that
      result in significant morbidity and mortality before or shortly after birth. We
      assessed the viral vector-mediated delivery of CRISPR-Cas9 or base editor 3 in
      utero, seeking therapeutic modification of Pcsk9 or Hpd in wild-type mice or the
      murine model of hereditary tyrosinemia type 1, respectively. We observed long
      term postnatal persistence of edited cells in both models, with reduction of
      plasma PCSK9 and cholesterol levels following in utero Pcsk9 targeting and rescue
      of the lethal phenotype of hereditary tyrosinemia type 1 following in utero Hpd
      targeting. The results of this proof-of-concept work demonstrate the possibility
      of efficiently performing gene editing before birth, pointing to a potential new
      therapeutic approach for selected congenital genetic disorders.

PMID- 30297904
TI  - Treatment of a metabolic liver disease by in vivo genome base editing in adult
      mice.
AB  - CRISPR-Cas-based genome editing holds great promise for targeting genetic
      disorders, including inborn errors of hepatocyte metabolism. Precise correction
      of disease-causing mutations in adult tissues in vivo, however, is challenging.
      It requires repair of Cas9-induced double-stranded DNA (dsDNA) breaks by homology
      directed mechanisms, which are highly inefficient in nondividing cells. Here we
      corrected the disease phenotype of adult phenylalanine hydroxylase (Pah)enu2
      mice, a model for the human autosomal recessive liver disease phenylketonuria
      (PKU)1, using recently developed CRISPR-Cas-associated base editors2-4. These
      systems enable conversion of C?G to T?A base pairs and vice versa, independent of
      dsDNA break formation and homology-directed repair (HDR). We engineered and
      validated an intein-split base editor, which allows splitting of the fusion
      protein into two parts, thereby circumventing the limited cargo capacity of adeno
      associated virus (AAV) vectors. Intravenous injection of AAV-base editor systems
      resulted in Pahenu2 gene correction rates that restored physiological blood
      phenylalanine (L-Phe) levels below 120 umol/l [5]. We observed mRNA correction
      rates up to 63%, restoration of phenylalanine hydroxylase (PAH) enzyme activity,
      and reversion of the light fur phenotype in Pahenu2 mice. Our findings suggest
      that targeting genetic diseases in vivo using AAV-mediated delivery of base
      editing agents is feasible, demonstrating potential for therapeutic application.

PMID- 30297905
TI  - Offering a choice between NIPT and invasive PND in prenatal genetic counseling:
      the impact of clinician characteristics on patients' test uptake.
AB  - Testing options for pregnant women at increased risk of common aneuploidies are
      non-invasive prenatal testing (NIPT) and invasive prenatal diagnosis (PND).
      Clinicians are challenged to comprehensively discuss the complex information in a
      patient-centered and non-directive manner, to allow for patients' informed
      decision-making. This study explored the information-centeredness, patient
      centeredness, and level of non-directivity of different clinicians and examined
      group differences between their patients. First, semi-structured interviews with
      four senior obstetricians and one senior nurse were held regarding their
      information provision, their adaptation of a patient-centered attitude, and their
      practice of non-directivity. Interviews were transcribed verbatim and rated by
      four independent researchers. Secondly, 181 pregnant women were included in the
      study, of whom 82% opted for NIPT and 18% chose PND. Between clinicians, we
      assessed the distribution of choice ratios, patients' impression of clinicians'
      test preferences, and patients' knowledge scores. The results indicate that
      clinicians do not differ in their information-centeredness, but do differ in
      their patient-centeredness and their level of non-directivity. Significant
      differences in patients' NIPT/PND ratios were observed between clinicians, with
      the largest difference being 35 vs. 4% opting for invasive PND. Between 9 and 22%
      of the patients had an impression of their clinician's preference and chose in
      accordance with this preference. Patients' overall knowledge scores did not
      differ across clinicians. In conclusion, the differences in NIPT/PND ratios
      between clinicians indicate that clinicians' differing counseling approaches
      affect the choices their patients make. The interviews indicate a possible
      framing effect which may unintentionally steer the decision-making process.

PMID- 30297906
TI  - The comprehensive mutational and phenotypic spectrum of TUBB8 in female
      infertility.
AB  - Human oocyte maturation is a precondition for fertilization and ensuing embryonic
      development. Previously, we identified TUBB8 variants as a genetic determinant of
      human oocyte maturation arrest and showed that these variants cause variable and
      mixed phenotypes in oocyte maturation and early embryo development. We also
      estimated that rare inherited or de novo variants in the TUBB8 gene accounted for
      30% of individuals in a small cohort of patients affected by oocyte maturation
      arrest. In the present study, we recruited a further 87 patients from unrelated
      families diagnosed with oocyte maturation or early embryonic arrest and
      identified 30 patients carrying TUBB8 variants. The corresponding phenotypes not
      only include oocyte maturation arrest, failure of fertilization, and early
      embryonic arrest, but also extend to the new phenotype of failure of embryo
      implantation. These observations provide the most detailed mutational and
      phenotypic spectrum of TUBB8, further extend the spectrum of variants and
      dysfunctional oocyte and embryo phenotypes caused by TUBB8 variants, and confirm
      previous findings for a critical role of TUBB8 during oocyte maturation and early
      embryonic development. Thus, TUBB8 mutation screening might not only be a genetic
      diagnostic marker for patients with oocyte maturation arrest, but might also have
      clinical implications for evaluating the competence of patients' functional
      oocytes with first polar body (PB1).

PMID- 30297907
TI  - Addendum: TGF-beta signaling alters H4K20me3 status via miR-29 and contributes to
      cellular senescence and cardiac aging.

PMID- 30297908
TI  - Structure-guided combination therapy to potently improve the function of mutant
      CFTRs.
AB  - Available corrector drugs are unable to effectively rescue the folding defects of
      CFTR-DeltaF508 (or CFTR-F508del ), the most common disease-causing mutation of
      the cystic fibrosis transmembrane conductance regulator, a plasma membrane (PM)
      anion channel, and thus to substantially ameliorate clinical phenotypes of cystic
      fibrosis (CF). To overcome the corrector efficacy ceiling, here we show that
      compounds targeting distinct structural defects of CFTR can synergistically
      rescue mutant expression and function at the PM. High-throughput cell-based
      screens and mechanistic analysis identified three small-molecule series that
      target defects at nucleotide-binding domain (NBD1), NBD2 and their membrane
      spanning domain (MSD) interfaces. Although individually these compounds
      marginally improve DeltaF508-CFTR folding efficiency, function and stability,
      their combinations lead to ~50-100% of wild-type-level correction in immortalized
      and primary human airway epithelia and in mouse nasal epithelia. Likewise,
      corrector combinations were effective against rare missense mutations in various
      CFTR domains, probably acting via structural allostery, suggesting a mechanistic
      framework for their broad application.

PMID- 30297909
TI  - Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma.
AB  - Preclinical studies suggest that treatment with neoadjuvant immune checkpoint
      blockade is associated with enhanced survival and antigen-specific T cell
      responses compared with adjuvant treatment1; however, optimal regimens have not
      been defined. Here we report results from a randomized phase 2 study of
      neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients
      with high-risk resectable melanoma ( NCT02519322 ). RECIST overall response rates
      (ORR), pathologic complete response rates (pCR), treatment-related adverse events
      (trAEs) and immune correlates of response were assessed. Treatment with combined
      ipilimumab and nivolumab yielded high response rates (RECIST ORR 73%, pCR 45%)
      but substantial toxicity (73% grade 3 trAEs), whereas treatment with nivolumab
      monotherapy yielded modest responses (ORR 25%, pCR 25%) and low toxicity (8%
      grade 3 trAEs). Immune correlates of response were identified, demonstrating
      higher lymphoid infiltrates in responders to both therapies and a more clonal and
      diverse T cell infiltrate in responders to nivolumab monotherapy. These results
      describe the feasibility of neoadjuvant immune checkpoint blockade in melanoma
      and emphasize the need for additional studies to optimize treatment regimens and
      to validate putative biomarkers.

PMID- 30297910
TI  - Wireless bioresorbable electronic system enables sustained nonpharmacological
      neuroregenerative therapy.
AB  - Peripheral nerve injuries represent a significant problem in public health,
      constituting 2-5% of all trauma cases1. For severe nerve injuries, even advanced
      forms of clinical intervention often lead to incomplete and unsatisfactory motor
      and/or sensory function2. Numerous studies report the potential of
      pharmacological approaches (for example, growth factors, immunosuppressants) to
      accelerate and enhance nerve regeneration in rodent models3-10. Unfortunately,
      few have had a positive impact in clinical practice. Direct intraoperative
      electrical stimulation of injured nerve tissue proximal to the site of repair has
      been demonstrated to enhance and accelerate functional recovery11,12, suggesting
      a novel nonpharmacological, bioelectric form of therapy that could complement
      existing surgical approaches. A significant limitation of this technique is that
      existing protocols are constrained to intraoperative use and limited therapeutic
      benefits13. Herein we introduce (i) a platform for wireless, programmable
      electrical peripheral nerve stimulation, built with a collection of circuit
      elements and substrates that are entirely bioresorbable and biocompatible, and
      (ii) the first reported demonstration of enhanced neuroregeneration and
      functional recovery in rodent models as a result of multiple episodes of
      electrical stimulation of injured nervous tissue.

PMID- 30297911
TI  - Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III
      melanoma.
AB  - Adjuvant ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) both improve relapse
      free survival of stage III melanoma patients1,2. In stage IV disease, the
      combination of ipilimumab + nivolumab is superior to ipilimumab alone and also
      appears to be more effective than nivolumab monotherapy3. Preclinical work
      suggests that neoadjuvant application of checkpoint inhibitors may be superior to
      adjuvant therapy4. To address this question and to test feasibility, 20 patients
      with palpable stage III melanoma were 1:1 randomized to receive ipilimumab 3 mg
      kg-1 and nivolumab 1 mg kg-1, as either four courses after surgery (adjuvant arm)
      or two courses before surgery and two courses postsurgery (neoadjuvant arm).
      Neoadjuvant therapy was feasible, with all patients undergoing surgery at the
      preplanned time point. However in both arms, 9/10 patients experienced one or
      more grade 3/4 adverse events. Pathological responses were achieved in 7/9 (78%)
      patients treated in the neoadjuvant arm. None of these patients have relapsed so
      far (median follow-up, 25.6 months). We found that neoadjuvant ipilimumab +
      nivolumab expand more tumor-resident T cell clones than adjuvant application.
      While neoadjuvant therapy appears promising, with the current regimen it induced
      high toxicity rates; therefore, it needs further investigation to preserve
      efficacy but reduce toxicity.

PMID- 30297912
TI  - Systemic messenger RNA as an etiological treatment for acute intermittent
      porphyria.
AB  - Acute intermittent porphyria (AIP) results from haploinsufficiency of
      porphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthesis
      pathway. Patients with AIP have neurovisceral attacks associated with increased
      hepatic heme demand. Phenobarbital-challenged mice with AIP recapitulate the
      biochemical and clinical characteristics of patients with AIP, including hepatic
      overproduction of the potentially neurotoxic porphyrin precursors. Here we show
      that intravenous administration of human PBGD (hPBGD) mRNA (encoded by the gene
      HMBS) encapsulated in lipid nanoparticles induces dose-dependent protein
      expression in mouse hepatocytes, rapidly normalizing urine porphyrin precursor
      excretion in ongoing attacks. Furthermore, hPBGD mRNA protected against
      mitochondrial dysfunction, hypertension, pain and motor impairment. Repeat dosing
      in AIP mice showed sustained efficacy and therapeutic improvement without
      evidence of hepatotoxicity. Finally, multiple administrations to nonhuman
      primates confirmed safety and translatability. These data provide proof-of
      concept for systemic hPBGD mRNA as a potential therapy for AIP.

PMID- 30297913
TI  - Transcriptomic responses of Serratia liquefaciens cells grown under simulated
      Martian conditions of low temperature, low pressure, and CO2-enriched anoxic
      atmosphere.
AB  - Results from previous experiments indicated that the Gram-negative alpha
      proteobacterium Serratia liquefaciens strain ATCC 27592 was capable of growth
      under low temperature (0  degrees C), low pressure (0.7 kPa), and anoxic, CO2
      dominated atmosphere-conditions intended to simulate the near-subsurface
      environment of Mars. To probe the response of its transcriptome to this extreme
      environment, S. liquefaciens ATCC 27592 was cultivated under 4 different
      environmental simulations: 0  degrees C, 0.7 kPa, CO2 atmosphere (Condition A); 0
      degrees C, ~101.3 kPa, CO2 atmosphere (Condition B); 0  degrees C, ~101.3 kPa,
      ambient N2/O2 atmosphere (Condition C); and 30  degrees C, ~101.3 kPa, N2/O2
      atmosphere (Condition D; ambient laboratory conditions). RNA-seq was performed on
      ribosomal RNA-depleted total RNA isolated from triplicate cultures grown under
      Conditions A-D and the datasets generated were subjected to transcriptome
      analyses. The data from Conditions A, B, or C were compared to laboratory
      Condition D. Significantly differentially expressed transcripts were identified
      belonging to a number of KEGG pathway categories. Up-regulated genes under all
      Conditions A, B, and C included those encoding transporters (ABC and PTS
      transporters); genes involved in translation (ribosomes and their biogenesis,
      biosynthesis of both tRNAs and aminoacyl-tRNAs); DNA repair and recombination;
      and non-coding RNAs. Genes down-regulated under all Conditions A, B, and C
      included: transporters (mostly ABC transporters); flagellar and motility
      proteins; genes involved in phenylalanine metabolism; transcription factors; and
      two-component systems. The results are discussed in the context of Mars
      astrobiology and planetary protection.

PMID- 30297914
TI  - Sexual Arousal Patterns of Identical Twins with Discordant Sexual Orientations.
AB  - Genetically identical twins can differ in their self-reported sexual
      orientations. However, whether the twins' subjective reports reflect valid
      differences in their sexual orientations is unknown. Measures of sexual
      orientation, which are free of the limitations of self-report, include genital
      arousal and pupil dilation while viewing sexual stimuli depicting men or women.
      We examined these responses in 6 male twin pairs and 9 female twin pairs who
      reported discordant sexual orientations. Across measures, heterosexual male twins
      responded more strongly to women than to men. Their homosexual co-twins showed an
      opposite pattern. Heterosexual female twins responded equally to both sexes,
      whereas their homosexual co-twins responded somewhat more to women than men.
      These differences within pairs were similar to differences between unrelated
      heterosexual and homosexual males and females. Our study provides physiological
      evidence confirming twins' discordant sexual orientations, thereby supporting the
      importance of the non-shared environment for the development of sexual
      orientation and sexual arousal.

PMID- 30297916
TI  - On-Chip Curing by Microwave for Long Term Usage of Electronic Devices in Harsh
      Environments.
AB  - Microwave-induced thermal curing is demonstrated to improve the reliability and
      to prolong the lifetime of chips containing nanoscale electron devices. A film
      containing graphite powder with high microwave absorbing efficiency was
      fabricated at low cost. The film is flexible, bendable, foldable, and attachable
      to a chip. A commercial off-the-shelf chip and a representative 3-dimensional
      (3D) metal-oxide-semiconductor field-effect transistor (MOSFET), known as FinFET,
      were utilized to verify the curing behaviors of the microwave-induced heat
      treatment. The heat effectively cured not only total ionizing dose (TID) damage
      from the external environment, but also internal electrical stress such as hot
      carrier injection (HCI), which are representative sources of damages in MOSFET
      insulators. Then, the characteristics of the pre- and post-curing electron
      devices are investigated using electrical measurements and numerical simulations.

PMID- 30297915
TI  - Multiple intrasyntenic rearrangements and rapid speciation in voles.
AB  - Remarkably stable genomic chromosome elements (evolutionary conserved segments or
      syntenies) are the basis of large-scale chromosome architecture in vertebrate
      species. However, these syntenic elements harbour evolutionary important changes
      through intrachromosomal rearrangements such as inversions and centromere
      repositioning. Here, using FISH with a set of 20 region-specific probes on a wide
      array of 28 species, we analyzed evolution of three conserved syntenic regions of
      the Arvicolinae ancestral karyotype. Inside these syntenies we uncovered
      multiple, previously cryptic intrachromosomal rearrangements. Although in each of
      the three conserved blocks we found inversions and centromere repositions, the
      blocks experienced different types of rearrangements. In two syntenies centromere
      repositioning predominated, while in the third region, paracentric inversions
      were more frequent, whereas pericentric inversions were not detected. We found
      that some of the intrachromosomal rearrangements, mainly paracentric inversions,
      were synapomorphic for whole arvicoline genera or tribes: genera Alexandromys and
      Microtus, tribes Ellobini and Myodini. We hypothesize that intrachromosomal
      rearrangements within conserved syntenic blocks are a major evolutionary force
      modulating genome architecture in species-rich and rapidly-evolving rodent taxa.
      Inversions and centromere repositioning may impact speciation and provide a
      potential link between genome evolution, speciation, and biogeography.

PMID- 30297917
TI  - DNA fingerprinting at farm level maps rice biodiversity across Bangladesh and
      reveals regional varietal preferences.
AB  - The development, dissemination, and adoption of improved rice varieties are
      imperative for global food and nutritional security. Knowledge of the crop's
      distribution across agro-ecologies is important for impact assessment studies,
      varietal replacement strategies, and the development and implementation of
      agricultural policies. Bangladesh is the world's 4th largest rice producer.
      Though traditional varieties (TVs) are abundant and valued throughout Bangladesh,
      population growth and vulnerability to climate change, necessitate efficient
      deployment of high-yielding stress-tolerant modern varieties (MVs). To aid
      agricultural policy and strategy this study aimed to accurately assess the
      distribution of MVs and TVs across Bangladesh during the rainfed rice-growing
      season. Information derived from a survey of rice production areas were compared
      and combined with DNA fingerprinting information from the same locations.
      Biodiversity of Bangladesh rice remained high. While TVs and first generation MVs
      of Bangladeshi and Indian origin were still commonly grown, recently released
      stress-tolerant MVs were adopted in large proportions in several districts.
      Although farmers successfully distinguished TVs from MVs grown in their fields, a
      considerable lack of authenticity among MVs was observed, pinpointing
      shortcomings in the seed supply chain. This study identifies focal points for
      extension work and validates DNA fingerprinting as reliable method for impact
      assessment studies.

PMID- 30297918
TI  - Policy options for reducing antibiotics and antibiotic-resistant genes in the
      environment.
AB  - Responses to the threat posed by antimicrobial resistance have been inadequate.
      Most attention has focused on the emergence of resistant organisms in human
      medicine and in agriculture. Much less attention has been given to antibiotic
      contamination of the environment. To assist health advocates to engage with this
      issue, we review the evidence on the role of agriculture, aquaculture, domestic
      waste and pharmaceutical manufacturing in the spread of antibiotic resistance,
      concluding that all of these activities pose a potentially serious threat. We
      then examine ways that this threat might be mitigated by specific measures, such
      as improved wastewater treatment processes, reduction of manufacturing emissions,
      consideration of environmental impacts in procurement and drug approval
      decisions, and better manure management. We conclude by placing this problem
      within the growing literature on commercial determinants of health, stressing the
      need for effective legislation and regulation developed independent of vested
      interests.

PMID- 30297920
TI  - GI Bleeding (Abstracts 530-567).

PMID- 30297921
TI  - Clinical Vignettes/Case Reports - Practice Management.

PMID- 30297919
TI  - Human blastocysts of normal and abnormal karyotypes display distinct
      transcriptome profiles.
AB  - Unveiling the transcriptome of human blastocysts can provide a wealth of
      important information regarding early embryonic ontology. Comparing the mRNA
      production of embryos with normal and abnormal karyotypes allows for a deeper
      understanding of the protein pathways leading to viability and aberrant fetal
      development. In addition, identifying transcripts specific for normal or abnormal
      chromosome copy number could aid in the search for secreted substances that could
      be used to non-invasively identify embryos best suited for IVF embryo transfer.
      Using RNA-seq, we characterized the transcriptome of 71 normally developing human
      blastocysts that were karyotypically normal vs. trisomic or monosomic. Every
      monosomy and trisomy of the autosomal and sex chromosomes were evaluated, mostly
      in duplicate. We first mapped the transcriptome of three normal embryos and found
      that a common core of more than 3,000 genes is expressed in all embryos. These
      genes represent pathways related to actively dividing cells, such as ribosome
      biogenesis and function, spliceosome, oxidative phosphorylation, cell cycle and
      metabolic pathways. We then compared transcriptome profiles of aneuploid embryos
      to those of normal embryos. We observed that non-viable embryos had a large
      number of dysregulated genes, some showing a hundred-fold difference in
      expression. On the contrary, sex chromosome abnormalities, XO and XXX displayed
      transcriptomes more closely mimicking those embryos with 23 normal chromosome
      pairs. Intriguingly, we identified a set of commonly deregulated genes in the
      majority of both trisomies and monosomies. This is the first paper demonstrating
      a comprehensive transcriptome delineation of karyotypic abnormalities found in
      the human pre-implantation embryo. We believe that this information will
      contribute to the development of new pre-implantation genetic screening methods
      as well as a better understanding of the underlying developmental abnormalities
      of abnormal embryos, fetuses and children.

PMID- 30297922
TI  - Biliary/Pancreas.

PMID- 30297924
TI  - Functional Bowel Disease.

PMID- 30297923
TI  - Clinical Vignettes/Case Reports - Obesity.

PMID- 30297925
TI  - Biliary/Pancreas.

PMID- 30297926
TI  - GI Bleeding.

PMID- 30297927
TI  - Esophagus.

PMID- 30297929
TI  - Stomach.

PMID- 30297928
TI  - Obesity.

PMID- 30297930
TI  - General Endoscopy.

PMID- 30297931
TI  - Clinical Vignettes/Case Reports - Stomach.

PMID- 30297932
TI  - Clinical Vignettes/Case Reports - Pediatrics.

PMID- 30297933
TI  - Clinical Vignettes/Case Reports - Functional Bowel Disease.

PMID- 30297934
TI  - Pediatrics.

PMID- 30297935
TI  - Small Intestine.

PMID- 30297936
TI  - Clinical Vignettes/Case Reports - Interventional Endoscopy.

PMID- 30297937
TI  - General Endoscopy.

PMID- 30297938
TI  - Colorectal Cancer Prevention.

PMID- 30297939
TI  - Esophagus.

PMID- 30297940
TI  - Inflammatory Bowel Disease.

PMID- 30297942
TI  - Clinical Vignettes/Case Reports - GI Bleeding.

PMID- 30297941
TI  - Clinical Vignettes/Case Reports - Small Intestine.

PMID- 30297943
TI  - Liver.

PMID- 30297944
TI  - Clinical Vignettes/Case Reports - Functional Bowel Disease.

PMID- 30297945
TI  - Small Intestine.

PMID- 30297947
TI  - Clinical Vignettes/Case Reports - General Endoscopy.

PMID- 30297946
TI  - Colon.

PMID- 30297948
TI  - Clinical Vignettes/Case Reports - Esophagus.

PMID- 30297950
TI  - Colorectal Cancer Prevention (Abstracts 217-313).

PMID- 30297952
TI  - Obesity.

PMID- 30297951
TI  - Clinical Vignettes/Case Reports - Biliary/Pancreas.

PMID- 30297953
TI  - Clinical Vignettes/Case Reports - Colorectal Cancer Prevention.

PMID- 30297954
TI  - Clinical Vignettes/Case Reports - Endoscopy Video Forum.

PMID- 30297955
TI  - Clinical Vignettes/Case Reports - Liver (Abstracts 3014-3054).

PMID- 30297956
TI  - Clinical Vignettes/Case Reports - Colorectal Cancer Prevention.

PMID- 30297957
TI  - Clinical Vignettes/Case Reports - Endoscopy Video Forum.

PMID- 30297958
TI  - Colon.

PMID- 30297959
TI  - Clinical Vignettes/Case Reports - Pediatrics.

PMID- 30297960
TI  - Clinical Vignettes/Case Reports - Practice Management.

PMID- 30297961
TI  - Interventional Endoscopy.

PMID- 30297962
TI  - Clinical Vignettes/Case Reports - Inflammatory Bowel Disease.

PMID- 30297965
TI  - Blocking CD122 might improve outcomes.

PMID- 30297964
TI  - Guide Swap enables genome-scale pooled CRISPR-Cas9 screening in human primary
      cells.
AB  - CRISPR-Cas9 screening allows genome-wide interrogation of gene function.
      Currently, to achieve the high and uniform Cas9 expression desirable for
      screening, one needs to engineer stable and clonal Cas9-expressing cells-an
      approach that is not applicable in human primary cells. Guide Swap permits genome
      scale pooled CRISPR-Cas9 screening in human primary cells by exploiting the
      unexpected finding that editing by lentivirally delivered, targeted guide RNAs
      (gRNAs) occurs efficiently when Cas9 is introduced in complex with nontargeting
      gRNA. We validated Guide Swap in depletion and enrichment screens in CD4+ T
      cells. Next, we implemented Guide Swap in a model of ex vivo hematopoiesis, and
      identified known and previously unknown regulators of CD34+ hematopoietic stem
      and progenitor cell (HSPC) expansion. We anticipate that this platform will be
      broadly applicable to other challenging cell types, and thus will enable
      discovery in previously inaccessible but biologically relevant human primary cell
      systems.

PMID- 30297963
TI  - The Duality of the MAPK Signaling Pathway in the Control of Metabolic Processes
      and Cellulase Production in Trichoderma reesei.
AB  - In this study, through global transcriptional analysis by RNA-Sequencing, we
      identified the main changes in gene expression that occurred in two functional
      mutants of the MAPK genes tmk1 and tmk2 in Trichoderma reesei during sugarcane
      bagasse degradation. We found that the proteins encoded by these genes regulated
      independent processes, sometimes in a cross-talk manner, to modulate gene
      expression in T. reesei. In the Deltatmk2 strain, growth in sugarcane bagasse
      modulated the expression of genes involved in carbohydrate metabolism, cell
      growth and development, and G-protein-coupled receptor-mediated cell signaling.
      On the other hand, deletion of tmk1 led to decreased expression of the major
      genes for cellulases and xylanases. Furthermore, TMK1 found to be involved in the
      regulation of the expression of major facilitator superfamily transporters. Our
      results revealed that the MAPK signaling pathway in T. reesei regulates many
      important processes that allow the fungus to recognize, transport, and metabolize
      different carbon sources during plant cell wall degradation.

PMID- 30297967
TI  - Genetic dissection of interspecific differences in yeast thermotolerance.
AB  - Some of the most unique and compelling survival strategies in the natural world
      are fixed in isolated species1. To date, molecular insight into these ancient
      adaptations has been limited, as classic experimental genetics has focused on
      interfertile individuals in populations2. Here we use a new mapping approach,
      which screens mutants in a sterile interspecific hybrid, to identify eight
      housekeeping genes that underlie the growth advantage of Saccharomyces cerevisiae
      over its distant relative Saccharomyces paradoxus at high temperature. Pro
      thermotolerance alleles at these mapped loci were required for the adaptive trait
      in S. cerevisiae and sufficient for its partial reconstruction in S. paradoxus.
      The emerging picture is one in which S. cerevisiae improved the heat resistance
      of multiple components of the fundamental growth machinery in response to
      selective pressure. Our study lays the groundwork for the mapping of genotype to
      phenotype in clades of sister species across Eukarya.

PMID- 30297966
TI  - Functional architecture of low-frequency variants highlights strength of negative
      selection across coding and non-coding annotations.
AB  - Common variant heritability has been widely reported to be concentrated in
      variants within cell-type-specific non-coding functional annotations, but little
      is known about low-frequency variant functional architectures. We partitioned the
      heritability of both low-frequency (0.5%<= minor allele frequency <5%) and common
      (minor allele frequency >=5%) variants in 40 UK Biobank traits across a broad set
      of functional annotations. We determined that non-synonymous coding variants
      explain 17 +/- 1% of low-frequency variant heritability ([Formula: see text])
      versus 2.1 +/- 0.2% of common variant heritability ([Formula: see text]). Cell
      type-specific non-coding annotations that were significantly enriched for
      [Formula: see text] of corresponding traits were similarly enriched for [Formula:
      see text] for most traits, but more enriched for brain-related annotations and
      traits. For example, H3K4me3 marks in brain dorsolateral prefrontal cortex
      explain 57 +/- 12% of [Formula: see text] versus 12 +/- 2% of [Formula: see text]
      for neuroticism. Forward simulations confirmed that low-frequency variant
      enrichment depends on the mean selection coefficient of causal variants in the
      annotation, and can be used to predict effect size variance of causal rare
      variants (minor allele frequency <0.5%).

PMID- 30297968
TI  - Integrative transcriptome analyses of the aging brain implicate altered splicing
      in Alzheimer's disease susceptibility.
AB  - Here we use deep sequencing to identify sources of variation in mRNA splicing in
      the dorsolateral prefrontal cortex (DLPFC) of 450 subjects from two aging
      cohorts. Hundreds of aberrant pre-mRNA splicing events are reproducibly
      associated with Alzheimer's disease. We also generate a catalog of splicing
      quantitative trait loci (sQTL) effects: splicing of 3,006 genes is influenced by
      genetic variation. We report that altered splicing is the mechanism for the
      effects of the PICALM, CLU and PTK2B susceptibility alleles. Furthermore, we
      performed a transcriptome-wide association study and identified 21 genes with
      significant associations with Alzheimer's disease, many of which are found in
      known loci, whereas 8 are in novel loci. These results highlight the convergence
      of old and new genes associated with Alzheimer's disease in autophagy-lysosomal
      related pathways. Overall, this study of the transcriptome of the aging brain
      provides evidence that dysregulation of mRNA splicing is a feature of Alzheimer's
      disease and is, in some cases, genetically driven.

PMID- 30297970
TI  - Public resources aid diabetes gene discovery.

PMID- 30297973
TI  - Fluid Deformation in Random Steady Three Dimensional Flow.
AB  - The deformation of elementary fluid volumes by velocity gradients is a key
      process for scalar mixing, chemical reactions and biological processes in flows.
      Whilst fluid deformation in unsteady, turbulent flow has gained much attention
      over the past half century, deformation in steady random flows with complex
      structure - such as flow through heterogeneous porous media - has received
      significantly less attention. In contrast to turbulent flow, the steady nature of
      these flows constrains fluid deformation to be anisotropic with respect to the
      fluid velocity, with significant implications for e.g. longitudinal and
      transverse mixing and dispersion. In this study we derive an ab initio coupled
      continuous time random walk (CTRW) model of fluid deformation in random steady
      three-dimensional flow that is based upon a streamline coordinate transform which
      renders the velocity gradient and fluid deformation tensors upper-triangular. We
      apply this coupled CTRW model to several model flows and find these exhibit a
      remarkably simple deformation structure in the streamline coordinate frame,
      facilitating solution of the stochastic deformation tensor components. These
      results show that the evolution of longitudinal and transverse fluid deformation
      for chaotic flows is governed by both the Lyapunov exponent and power-law
      exponent of the velocity PDF at small velocities, whereas algebraic deformation
      in non-chaotic flows arises from the intermittency of shear events following
      similar dynamics as that for steady two-dimensional flow.

PMID- 30297972
TI  - Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights
      from the Sarcomeric Human Cardiomyopathy Registry (SHaRe).
AB  - Background: A better understanding of the factors that contribute to
      heterogeneous outcomes and lifetime disease burden in hypertrophic cardiomyopathy
      (HCM) is critically needed to improve patient management and outcomes. The
      Sarcomeric Human Cardiomyopathy Registry (SHaRe) was established to provide the
      scale of data required to address these issues, aggregating longitudinal datasets
      curated by eight international HCM specialty centers. Methods: Data on 4591 HCM
      patients (2763 genotyped), followed for a mean of 5.4+/-6.9 years (24,791 patient
      years; median [interquartile range] 2.9 [0.3-7.9] years) were analyzed regarding
      cardiac arrest, cardiac transplantation, appropriate implantable cardioverter
      defibrillator (ICD) therapy, all-cause death, atrial fibrillation, stroke, New
      York Heart Association Functional Class III/IV symptoms (all comprising the
      overall composite endpoint), and left ventricular ejection fraction (LVEF)<35%.
      Outcomes were analyzed individually and as composite endpoints. Results: Median
      age of diagnosis was 45.8 [30.9-58.1] years and 37% of patients were female. Age
      of diagnosis and sarcomere mutation status were predictive of outcomes. Patients
      <40 years old at diagnosis had a 77% [95% confidence interval: 72%, 80%]
      cumulative incidence of the overall composite outcome by age 60, compared to 32%
      [29%, 36%] by age 70 for patients diagnosed >60 years. Young HCM patients (20-29
      years) had 4-fold higher mortality than the general United States population at a
      similar age. Patients with pathogenic/likely pathogenic sarcomere mutations had
      two-fold greater risk for adverse outcomes compared to patients without
      mutations; sarcomere variants of uncertain significance were associated with
      intermediate risk. Heart failure and atrial fibrillation were the most prevalent
      adverse events, although typically not emerging for several years after
      diagnosis. Ventricular arrhythmias occurred in 32% [23%, 40%] of patients <40
      years at diagnosis, but in 1% [1%, 2%] >60 years. Conclusions: The cumulative
      burden of HCM is substantial and dominated by heart failure and atrial
      fibrillation occurring many years following diagnosis. Young age of diagnosis and
      the presence of a sarcomere mutation are powerful predictors of adverse outcomes.
      These findings highlight the need for close surveillance throughout life, and the
      need to develop disease-modifying therapies.

PMID- 30297969
TI  - Fine-mapping type 2 diabetes loci to single-variant resolution using high-density
      imputation and islet-specific epigenome maps.
AB  - We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from
      898,130 European-descent individuals (9% cases), after imputation to high-density
      reference panels. With these data, we (i) extend the inventory of T2D-risk
      variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403
      distinct association signals); (ii) enrich discovery of lower-frequency risk
      alleles (80 index variants with minor allele frequency <5%, 14 with estimated
      allelic odds ratio >2); (iii) substantially improve fine-mapping of causal
      variants (at 51 signals, one variant accounted for >80% posterior probability of
      association (PPA)); (iv) extend fine-mapping through integration of tissue
      specific epigenomic information (islet regulatory annotations extend the number
      of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18
      genes with associations attributable to coding variants); and (vi) demonstrate
      enhanced potential for clinical translation (genome-wide chip heritability
      explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk
      score differ more than ninefold in prevalence).

PMID- 30297974
TI  - Formal (4+1)-Cyclization of Ammonium Ylides with Vinylogous para-Quinone
      Methides.
AB  - The formal (4+1)-cyclization between in situ generated achiral carbonyl
      stabilized ammonium ylides and vinylogous p-quinone methides can be carried out
      under operationally simple conditions, leading to two different double bond
      regioisomers depending on the used conditions. Besides these racemic approaches,
      also a first proof-of-concept for enantioselective versions of these reactions
      has been obtained.

PMID- 30297971
TI  - Allele-defined genome of the autopolyploid sugarcane Saccharum spontaneum L.
AB  - Modern sugarcanes are polyploid interspecific hybrids, combining high sugar
      content from Saccharum officinarum with hardiness, disease resistance and
      ratooning of Saccharum spontaneum. Sequencing of a haploid S. spontaneum, AP85
      441, facilitated the assembly of 32 pseudo-chromosomes comprising 8 homologous
      groups of 4 members each, bearing 35,525 genes with alleles defined. The
      reduction of basic chromosome number from 10 to 8 in S. spontaneum was caused by
      fissions of 2 ancestral chromosomes followed by translocations to 4 chromosomes.
      Surprisingly, 80% of nucleotide binding site-encoding genes associated with
      disease resistance are located in 4 rearranged chromosomes and 51% of those in
      rearranged regions. Resequencing of 64 S. spontaneum genomes identified balancing
      selection in rearranged regions, maintaining their diversity. Introgressed S.
      spontaneum chromosomes in modern sugarcanes are randomly distributed in AP85-441
      genome, indicating random recombination among homologs in different S. spontaneum
      accessions. The allele-defined Saccharum genome offers new knowledge and
      resources to accelerate sugarcane improvement.

PMID- 30297975
TI  - Vowel Formant Dispersion Reflects Severity of Apraxia of Speech.
AB  - Background: Apraxia of Speech (AOS) has been associated with deviations in
      consonantal voice-onset-time (VOT), but studies of vowel acoustics have yielded
      conflicting results. However, a speech motor planning disorder that is not bound
      by phonological categories is expected to affect vowel as well as consonant
      articulations. Aims: We measured consonant VOTs and vowel formants produced by a
      large sample of stroke survivors, and assessed to what extent these variables and
      their dispersion are predictive of AOS presence and severity, based on a scale
      that uses clinical observations to rate gradient presence of AOS, aphasia, and
      dysarthria. Methods & Procedures: Picture-description samples were collected from
      53 stroke survivors, including unimpaired speakers (12) and speakers with
      primarily aphasia (19), aphasia with AOS (12), primarily AOS (2), aphasia with
      dysarthria (2), and aphasia with AOS and dysarthria (6). The first three formants
      were extracted from vowel tokens bearing main stress in open-class words, as well
      as VOTs for voiced and voiceless stops. Vowel space was estimated as reflected in
      the formant centralization ratio. Stepwise Linear Discriminant Analyses were used
      to predict group membership, and ordinal regression to predict AOS severity,
      based on the absolute values of these variables, as well as the standard
      deviations of formants and VOTs within speakers. Outcomes and Results: Presence
      and severity of AOS were most consistently predicted by the dispersion of F1, F2,
      and voiced-stop VOT. These phonetic-acoustic measures do not correlate with
      aphasia severity. Conclusions: These results confirm that the AOS affects
      articulation across-the-board and does not selectively spare vowel production.

PMID- 30297976
TI  - Force detection, center of pressure tracking, and energy harvesting from a
      piezoelectric knee implant.
AB  - Recent developments in the field of orthopedic materials and procedures have made
      the total knee replacement (TKR) an option for people who suffer from knee
      diseases and injuries. One of the ongoing debates in this area involves the
      correlation of postoperative joint functionality to intraoperative alignment. Due
      to a lack of in vivo data from the knee joint after surgery, the establishment of
      a well-quantified alignment method is hindered. In order to obtain information
      about knee function after the operation, the design of a self-powered
      instrumented knee implant is proposed in this study. The design consists of a
      total knee replacement bearing equipped with four piezoelectric transducers
      distributed in the medial and lateral compartments. The piezoelectric transducers
      are utilized to measure the total axial force applied on the tibial bearing
      through the femoral component of the joint, as well as to track the movement in
      the center of pressure (CoP). In addition, the generated voltage from the
      piezoelectrics can be harvested and stored to power embedded electronics for
      further signal conditioning and data transmission purposes. Initially, finite
      element (FE) analysis is performed on the knee bearing to select the best
      location of the transducers with regards to sensing the total force and location
      of the CoP. A series of experimental tests are then performed on a fabricated
      prototype which aim to investigate the sensing and energy harvesting performance
      of the device. Piezoelectric force and center of pressure measurements are
      compared to actual experimental quantities for twelve different relative
      positions of the femoral component and bearing of the knee implant in order to
      evaluate the performance of the sensing system. The output voltage of the
      piezoelectric transducers is measured across a load resistance to determine the
      optimum extractable power, and then rectified and stored in a capacitor to
      evaluate the realistic energy harvesting ability of the system. The results show
      only a small level of error in sensing the force and the location of the CoP.
      Additionally, a maximum power of 269.1 MUW is achieved with a 175 kOmega optimal
      resistive load, and a 4.9 V constant voltage is stored in a 3.3 mF capacitor
      after 3333 loading cycles. The sensing and energy harvesting results present the
      promising potential of this system to be used as an integrated self-powered
      instrumented knee implant.

PMID- 30297977
TI  - Health Care Resource Utilization and Costs among Adult Patients with Advanced
      Soft Tissue Sarcoma: A Retrospective Medical Record Review in the United Kingdom,
      Spain, Germany, and France.
AB  - Objective: To describe health care resource utilization and costs for patients
      with advanced soft tissue sarcoma (STS) in the United Kingdom (UK), Spain,
      Germany, and France. Methods: Physicians abstracted data for adult patients with
      a diagnosis of advanced STS (other than Kaposi's sarcoma or gastrointestinal
      stromal tumor) who received >=1 lines of systemic therapy. Health care resource
      utilization related to advanced STS treatment was recorded; associated costs were
      estimated by applying unit costs. Results: A total of 130 physicians provided
      data for 807 patients (UK: 199; Spain: 203; Germany: 204; and France: 201). The
      site of care during active treatment varied based on differences in the health
      care systems of these four countries. Total mean per-patient health care cost in
      the UK was L19,457; in Spain, ?26,814; in Germany, ?20,468; and in France,
      ?24,368. Advanced STS-related systemic treatment costs were driven primarily by
      drug acquisition and administration costs. Treatment-related costs increased
      during later lines of therapy for all countries except France, where they
      decreased after first-line therapy. Pain control and antiemetics were the most
      common supportive care medications. Conclusions: This study provides real-world
      data on resource utilization and estimated costs in advanced STS and could inform
      policymakers about treatment burden.

PMID- 30297978
TI  - Corrigendum to "Formononetin Administration Ameliorates Dextran Sulfate Sodium
      Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway".
AB  - [This corrects the article DOI: 10.1155/2018/3048532.].

PMID- 30297979
TI  - Search Smart for Your Health - A Statewide Health Literacy Campaign.
AB  - The Georgia Health Sciences Library Association (GHSLA) and the Georgia Alliance
      for Health Literacy (GAHL) partnered to educate residents about reliable health
      information online to raise health literacy awareness across the state of
      Georgia. The two groups received a gubernatorial declaration designating October
      as Health Literacy Month in Georgia. Information was posted online and
      demonstration workshops were held. The networking opportunities that resulted
      have allowed for additional partnerships and grant support to address the vital
      health literacy information needs of those with health disparities through
      clinician training and additional workshops.

PMID- 30297980
TI  - Cognitive Rehabilitation of Adaptive Behavior in Children with Neurodevelopmental
      Disorders: A Meta-Analysis.
AB  - Objectives: Negative behavioral problems often occur following the onset of
      neurodevelopmental disorders and have an overall impact on the affected children,
      specifically in terms of their social developmental level. In children, social
      development behavior has been shown to spontaneously mature over time with the
      cognitive therapy intervention effects. This study performed a meta-analysis to
      provide a statistical synopsis of the available evidence of social development
      behavioral changes following cognitive therapy in children with
      neurodevelopmental disorders. Methods: Data was collected from two online search
      engines, including EBSCOhost and PubMed, from January 1, 2006, to August 31,
      2016, using the terms "cognition," "cognitive function," and "disease including
      neurodevelopmental disorder with DSM-5." Two assessors searched the literature
      using independent inclusion criteria and evaluated the quality of results using
      the Jadad score. Six articles were chosen using the Comprehensive Meta-Analysis
      program (version 2.0). Results: Six articles reporting randomized controlled
      trial studies were included. The effective scores for improving adaptive behavior
      following cognitive therapy in children with neurodevelopmental disorder were
      0.64. The effective score of adaptive behavior was significant in this study (p <
      0.05). The results showed no significant statistical heterogeneity and
      publication bias. Conclusions: The findings of the meta-analysis suggest that
      cognitive interventions are effective at improving adaptive behavior associated
      with neurodevelopmental disorders.

PMID- 30297982
TI  - Fragile X-Associated Disorders in Serbia: Baseline Quantitative and Qualitative
      Survey of Knowledge, Attitudes and Practices Among Medical Professionals.
AB  - We conducted a knowledge, attitude, and practice (KAP) survey of fragile X
      associated disorders (FXD) in Serbia in order to obtain baseline quantitative and
      qualitative KAP data on fragile X mental retardation 1 gene (FMR1) pre- and full
      mutations (PM, FM). The survey's 16-item questionnaire included a knowledge
      component (12/16), such as self-assessment knowledge (SAK) and factual knowledge
      (FK, 2/5 questions for PM, FXTAS and FXPOI). Education-directed attitudes in the
      FXD field and FMR1 DNA testing practices had 4/16 items, including brief case
      vignettes of FXTAS and FXPOI, respectively. The study's cohort consisted of
      primary care physicians (referred to as "physicians" in the rest of the text)
      throughout Serbia (n = 284, aged 26-64 years, 176/284, 62.2% in Belgrade, Serbia)
      and senior medical students (n = 245, aged 23-30 years; 33.5% males) at the
      Belgrade School of Medicine. Strikingly, half of the survey respondents indicated
      "not having any" knowledge for the fragile X gene premutation and FXD. Physicians
      were more likely to indicate "not having any" knowledge than students (41.2% of
      physicians vs. 13.1% of students, P < 0.05). Roughly half of the students had
      "minimal knowledge" (53.5 vs. 30.5% of physicians, P < 0.05). Low FK was common
      in the cohort, as few physicians had "all correct answers" (7.5 vs. 3.7% of
      students, P < 0.05; 16.5 vs. 9.5% of students for the 2/5 premutation-related
      questions). Statistical analyses identified physicians' practice setting and
      length of clinical experience as predictors of the lack of FK on questions
      related to FXD. Physicians were more likely than students to indicate "strongly
      agreed" to expand their knowledge of the gene premutation and FXD (90.9 vs. 66.7%
      of students, P < 0.01). However, students more frequently indicated that they are
      willing to recommend DNA testing in their future practices than physicians (93.5
      vs. 64.8% of physicians, P < 0.001). In conclusion, there is a major gap in
      knowledge regarding fragile X gene PM and FXD among the study's participants in
      Serbia. The study's informative-educational survey serves as an initial step in
      the process of enhancing the KAP of medical professionals with regards to the
      fragile X gene premutation and FXD.

PMID- 30297981
TI  - Cortical Network Synchrony Under Applied Electrical Field in vitro.
AB  - Synchronous network activity plays a crucial role in complex brain functions.
      Stimulating the nervous system with applied electric field (EF) is a common tool
      for probing network responses. We used a gold wire-embedded silk protein film
      based interface culture to investigate the effects of applied EFs on random
      cortical networks of in vitro cultures. Two-week-old cultures were exposed to EF
      of 27 mV/mm for <1 h and monitored by time-lapse calcium imaging. Network
      activity was represented by calcium signal time series mapped to source neurons
      and analyzed by using a community detection algorithm. Cortical cultures
      exhibited large scale, synchronized oscillations under alternating EF of changing
      frequencies. Field polarity and frequency change were both found to be necessary
      for network synchrony, as monophasic pulses of similar frequency changes or EF of
      a constant frequency failed to induce correlated activities of neurons. Group
      specific oscillatory patterns were entrained by network-level synchronous
      oscillations when the alternating EF frequency was increased from 0.2 Hz to 200
      kHz. Binary responses of either activity increase or decrease contributed to the
      opposite phase patterns of different sub-populations. Conversely, when the EF
      frequency decreased over the same range span, more complex behavior emerged
      showing group-specific amplitude and phase patterns. These findings formed the
      basis of a hypothesized network control mechanism for temporal coordination of
      distributed neuronal activity, involving coordinated stimulation by alternating
      polarity, and time delay by change of frequency. These novel EF effects on random
      neural networks have important implications for brain functional studies and
      neuromodulation applications.

PMID- 30297983
TI  - Loss of the Cochlear Amplifier Prestin Reduces Temporal Processing Efficacy in
      the Central Auditory System.
AB  - Active mechanical amplification of sound occurs in cochlear outer hair cells
      (OHCs) that change their length with oscillations of their membrane potential.
      Such length changes are the proposed cellular source of the cochlear amplifier,
      and prestin is the motor protein responsible for OHC electromotility. Previous
      findings have shown that mice lacking prestin displayed a loss of OHC
      electromotility, subsequent loss of distortion-product otoacoustic emissions, and
      a 40-60 dB increase in hearing thresholds. In this study we were interested in
      studying the functional consequences of the complete loss of cochlear
      amplification on neural coding of frequency selectivity, tuning, and temporal
      processing in the auditory midbrain. We recorded near-field auditory evoked
      potentials and multi-unit activity from the inferior colliculus (IC) of prestin (
      /-) null and prestin (+/+) wild-type control mice and determined frequency
      response areas (FRAs), tuning sharpness, and gap detection to tone bursts and
      silent gaps embedded in broadband noise. We were interested in determining if the
      moderate to severe sensorineural hearing loss associated with the loss of motor
      protein prestin would also impair auditory midbrain temporal-processing measures,
      or if compensatory mechanisms within the brainstem could compensate for the loss
      of prestin. In prestin knockout mice we observed that there are severe
      impairments in midbrain tuning, thresholds, excitatory drive, and gap detection
      suggesting that brainstem and midbrain processing could not overcome the auditory
      processing deficits afforded by the loss of OHC electromotility mediated by the
      prestin protein.

PMID- 30297984
TI  - Effective Knockdown of Gene Expression in Primary Microglia With siRNA and
      Magnetic Nanoparticles Without Cell Death or Inflammation.
AB  - Microglia, the resident immune cells of the brain, have multiple functions in
      physiological and pathological conditions, including Alzheimer's disease (AD).
      The use of primary microglial cell cultures has proved to be a valuable tool to
      study microglial biology under various conditions. However, more advanced
      transfection methodologies for primary cultured microglia are still needed, as
      current methodologies provide low transfection efficiency and induce cell death
      and/or inflammatory activation of the microglia. Here, we describe an easy, and
      effective method based on the Glial-Mag method (OZ Biosciences) using magnetic
      nanoparticles and a magnet to successfully transfect primary microglia cells with
      different small interfering RNAs (siRNAs). This method does not require
      specialist facilities or specific training and does not induce cell toxicity or
      inflammatory activation. We demonstrate that this protocol successfully decreases
      the expression of two key genes associated with AD, the triggering receptor
      expressed in myeloid cells 2 (TREM2) and CD33, in primary microglia cell
      cultures.

PMID- 30297985
TI  - Innovative Optogenetic Strategies for Vision Restoration.
AB  - The advent of optogenetics has ushered in a new era in neuroscience where
      spatiotemporal control of neurons is possible through light application. These
      tools used to study neural circuits can also be used therapeutically to restore
      vision. In order to recapitulate the broad spectral and light sensitivities along
      with high temporal sensitivity found in human vision, researchers have identified
      and developed new optogenetic tools. There are two major kinds of optogenetic
      effectors employed in vision restoration: ion channels and G-protein coupled
      receptors (GPCRs). Ion channel based optogenetic therapies require high intensity
      light that can be unsafe at lower wavelengths, so work has been done to expand
      and red-shift the excitation spectra of these channels. Light activatable GPCRs
      are much more sensitive to light than their ion channel counterparts but are
      slower kinetically in terms of both activation and inactivation. This review
      article examines the latest optogenetic ion channel and GPCR candidates for
      vision restoration based on light and temporal sensitivity.

PMID- 30297987
TI  - Comparing Mouse and Rat Hippocampal Place Cell Activities and Firing Sequences in
      the Same Environments.
AB  - Hippocampal place cells are key to spatial representation and spatial memory
      processing. They fire at specific locations in a space (place fields) and fire in
      precise patterns during theta sequences and during ripple-associated replay
      events. These phenomena have been extensively studied in rats, but to a less
      extent in mice. The availability of versatile genetic manipulations gives mice an
      advantage for place cell studies. However, it is unknown how place fields and
      place cell sequences in the same environment differ between mice and rats. Here,
      we provide a quantitative comparison in place field properties, as well as theta
      sequences and replays, between rats and mice as they ran on the same novel track
      and as they rested afterwards. We found that place cells in mice display less
      spatial specificity with more but smaller place fields. Theta oscillations, theta
      phase precession and aspects of theta sequences in mice are similar as those in
      rats. The ripple-associated replay, however, is relatively rare during stopping
      on the novel track in mice. The replay is present during resting after the track
      running, but is weaker in mice than the replay in rats. Our results suggest that
      place cells in mice and rats are qualitatively similar, but with substantial
      quantitative differences.

PMID- 30297986
TI  - The Role of KLF4 in Alzheimer's Disease.
AB  - Kruppel-like factor 4 (KLF4), a member of the family of zinc-finger transcription
      factors, is widely expressed in range of tissues that play multiple functions.
      Emerging evidence suggest KLF4's critical regulatory effect on the
      neurophysiological and neuropathological processes of Alzheimer's disease (AD),
      indicating that KLF4 might be a potential therapeutic target of neurodegenerative
      diseases. In this review, we will summarize relevant studies and illuminate the
      regulatory role of KLF4 in the neuroinflammation, neuronal apoptosis, axon
      regeneration and iron accumulation to clarify KLF4's status in the pathogenesis
      of AD.

PMID- 30297989
TI  - Sex Differences in Rhesus Monkeys' Digit Ratio (2D:4D Ratio) and Its Association
      With Maternal Social Dominance Rank.
AB  - Prenatal androgen exposure (PAE) plays a pivotal role in masculinizing the
      developing body and brain, and extreme exposure may contribute to autism, anxiety
      disorder and schizophrenia. One commonly used biomarker for PAE is the pointer-to
      ring-finger digit length (2D:4D) ratio. Although this biomarker is widely used in
      human studies, relatively few studies have investigated 2D:4D ratio in nonhuman
      primates, particularly rhesus macaques (Macaca mulatta), one of the most commonly
      used animals in biomedical research. Thus far, data suggest that sexual
      dimorphism in 2D:4D ratio may be in the opposite direction in some monkey
      species, when compared to the pattern exhibited by humans and great apes. Using a
      large sample size, we investigated whether rhesus monkeys' 2D:4D ratio shows the
      same sex-differentiated pattern present in other Old World monkey species. We
      also investigated whether individual differences in 2D:4D ratio are associated
      with the social dominance rank of subjects' mothers during pregnancy, and the
      social dominance rank the subjects attained as adults. Subjects were 335 rhesus
      monkeys between 3 years and 24 years of age (M = 6.6). Maternal dominance rank
      during pregnancy and subjects' adult dominance rank were categorized into
      tertiles (high, middle and low). Results showed that, across both hands, male
      rhesus monkeys exhibited higher 2D:4D ratio than females, a pattern consistent
      with other monkey species and a reversal from the pattern typically observed in
      humans and apes. This sex difference was modulated by maternal dominance rank,
      with female offspring of high-ranking and middle-ranking mothers exhibiting
      masculinized 2D:4D ratio, indicating that maternal dominance rank during
      pregnancy may influence levels of PAE. There was no association between subjects'
      2D:4D ratio and the social dominance rank they attained as adults. These findings
      show a consistent sex difference in Old World monkeys' 2D:4D ratio that diverges
      from the pattern observed in apes and humans, and suggest maternal social
      dominance rank modulates PAE in rhesus monkeys.

PMID- 30297988
TI  - The Immediate Effect of Therapeutic Touch and Deep Touch Pressure on Range of
      Motion, Interoceptive Accuracy and Heart Rate Variability: A Randomized
      Controlled Trial With Moderation Analysis.
AB  - Background: There is paucity in the literature regarding the role of the
      interoceptive pathway through the insular cortex (IC), as well as heart rate
      variability (HRV) in relation to Osteopathic Manipulative Therapy (OMT) and deep
      touch. Aims: The present study investigated whether both OMT treatment and deep
      touch (a newly hypothesized treatment option) was effective at altering the
      interoceptive pathway and HRV, whilst OMT was only expected to be effective for
      increasing Range of Motion (ROM). Methods: Thirty-five healthy volunteers were
      randomly allocated into three conditions in a repeated measures crossover design;
      a control (laying supine on a plinth); deep-touch (head cradling); and an
      osteopathic mobilization therapeutic technique on the temporomandibular joint
      (TMJ). Interoceptive accuracy (IAc), HRV, as well as range of motion (ROM) for
      the TMJ area as well as the cervical spine (Csp) right and left measures were
      taken pre and post each condition setting. Results: Significant condition effects
      emerged from the deep-touch and mobilization interventions for IAc where
      increases were identified through planned comparisons. For the HRV measure
      (RMSSD), a significant effect emerged in the deep-touch condition (increase) but
      not in the mobilization or control conditions. ROM did not increase for any
      condition. IAc correlated with post-ROM outcomes in many cases and HRV moderated
      some of these relations. Conclusion: These results are discussed in the context
      of clinical practice, where cranial deep-touch maybe an effective treatment and
      modulator of the parasympathetic nervous systems, as well as the interoceptive
      system.

PMID- 30297990
TI  - Mice With Partial Deletion of Y-Heterochromatin Exhibits Stress Vulnerability.
AB  - The role of Y chromosome in sex determination and male fertility is well
      established. It is also known that infertile men are prone to psychological
      disturbances. Earlier studies in the laboratory identified genes expressed in
      testes that are putatively regulated by Y chromosome in man and mouse. With the
      availability of a Y-deleted mouse model, that is subfertile, we studied the
      effect of a partial deletion of Y-chromosomal heterochromatin on mouse behavior
      when compared to its wild type. The partial Y-deleted mice exhibited anxiety like
      phenotype under stress when different anxiety (open field test and elevated plus
      maze, EPM test) and depression related tests (tail suspension and force swim)
      were performed. The mutant mice also showed reduction in hippocampal neurogenesis
      and altered expression of neurogenesis markers such as Nestin, Sox2, Gfap,
      NeuroD1 and Dcx using quantitative real time PCR (qPCR) analysis. The genes with
      altered expression contained short stretches of homology to Y-derived transcripts
      only in their Untranslated Regions (UTRs). Our study suggests putative regulation
      of these genes by the Y chromosome in mouse brain altering stress related
      behavior.

PMID- 30297991
TI  - Theta Activity in the Left Dorsal Premotor Cortex During Action Re-Evaluation and
      Motor Reprogramming.
AB  - The ability to rapidly adjust our actions to changes in the environment is a key
      function of human motor control. Previous work implicated the dorsal premotor
      cortex (dPMC) in the up-dating of action plans based on environmental cues. Here
      we used electroencephalography (EEG) to identify neural signatures of up-dating
      cue-action relationships in the dPMC and connected frontoparietal areas. Ten
      healthy subjects performed a pre-cued alternate choice task. Simple geometric
      shapes cued button presses with the right or left index finger. The shapes of the
      pre-cue and go-cue differed in two third of trials. In these incongruent trials,
      the go-cue prompted a re-evaluation of the pre-cued action plan, slowing response
      time relative to trials with identical cues. This re-evaluation selectively
      increased theta band activity without modifying activity in alpha and beta band.
      Source-based analysis revealed a widespread theta increase in dorsal and mesial
      frontoparietal areas, including dPMC, supplementary motor area (SMA), primary
      motor and posterior parietal cortices (PPC). Theta activity scaled positively
      with response slowing and increased more strongly when the pre-cue was invalid
      and required subjects to select the alternate response. Together, the results
      indicate that theta activity in dPMC and connected frontoparietal areas is
      involved in the re-adjustment of cue-induced action tendencies.

PMID- 30297992
TI  - Substance-Specific Differences in Human Electroencephalographic Burst Suppression
      Patterns.
AB  - Different anesthetic agents induce burst suppression in the electroencephalogram
      (EEG) at very deep levels of general anesthesia. EEG burst suppression has been
      identified to be a risk factor for postoperative delirium (POD). EEG based
      automated detection algorithms are used to detect burst suppression patterns
      during general anesthesia and a burst suppression ratio (BSR) is calculated.
      Unfortunately, applied algorithms do not give information as precisely as
      suggested, often resulting in an underestimation of the patients' burst
      suppression level. Additional knowledge of substance-specific burst suppression
      patterns could be of great importance to improve the ability of EEG based
      monitors to detect burst suppression. In a re-analysis of EEG recordings obtained
      from a previous study, we analyzed EEG data of 45 patients undergoing elective
      surgery under general anesthesia. The patients were anesthetized with
      sevoflurane, isoflurane or propofol (n = 15, for each group). After skin
      incision, the used agent was titrated to a level when burst suppression occurred.
      In a visual analysis of the EEG, blinded to the used anesthetic agent, we
      included the first distinct burst in our analysis. To avoid bias through changing
      EEG dynamics throughout the burst, we only focused on the first 2 s of the burst.
      These episodes were analyzed using the power spectral density (PSD) and
      normalized PSD, the absolute burst amplitude and absolute burst slope, as well as
      permutation entropy (PeEn). Our results show significant substance-specific
      differences in the architecture of the burst. Volatile-induced bursts showed
      higher burst amplitudes and higher burst power. Propofol-induced bursts had
      significantly higher relative power in the EEG alpha-range. Further, isoflurane
      induced bursts had the steepest burst slopes. We can present the first systematic
      comparison of substance-specific burst characteristics during anesthesia.
      Previous observations, mostly derived from animal studies, pointing out the
      substance-specific differences in bursting behavior, concur with our findings.
      Our findings of substance-specific EEG characteristics can provide information to
      help improve automated burst suppression detection in monitoring devices. More
      specific detection of burst suppression may be helpful to reduce excessive EEG
      effects of anesthesia and therefore the incidence of adverse outcomes such as
      POD.

PMID- 30297993
TI  - Markov Model-Based Method to Analyse Time-Varying Networks in EEG Task-Related
      Data.
AB  - The dynamic nature of functional brain networks is being increasingly recognized
      in cognitive neuroscience, and methods to analyse such time-varying networks in
      EEG/MEG data are required. In this work, we propose a pipeline to characterize
      time-varying networks in single-subject EEG task-related data and further,
      evaluate its validity on both simulated and experimental datasets. Pre-processing
      is done to remove channel-wise and trial-wise differences in activity. Functional
      networks are estimated from short non-overlapping time windows within each
      "trial," using a sparse-MVAR (Multi-Variate Auto-Regressive) model. Functional
      "states" are then identified by partitioning the entire space of functional
      networks into a small number of groups/symbols via k-means clustering.The multi
      trial sequence of symbols is then described by a Markov Model (MM). We show
      validity of this pipeline on realistic electrode-level simulated EEG data, by
      demonstrating its ability to discriminate "trials" from two experimental
      conditions in a range of scenarios. We then apply it to experimental data from
      two individuals using a Brain-Computer Interface (BCI) via a P300 oddball task.
      Using just the Markov Model parameters, we obtain statistically significant
      discrimination between target and non-target trials. The functional networks
      characterizing each 'state' were also highly similar between the two individuals.
      This work marks the first application of the Markov Model framework to infer time
      varying networks from EEG/MEG data. Due to the pre-processing, results from the
      pipeline are orthogonal to those from conventional ERP averaging or a typical EEG
      microstate analysis. The results provide powerful proof-of-concept for a Markov
      model-based approach to analyzing the data, paving the way for its use to track
      rapid changes in interaction patterns as a task is being performed. MATLAB code
      for the entire pipeline has been made available.

PMID- 30297995
TI  - The Head Turning Modulation System: An Active Multimodal Paradigm for
      Intrinsically Motivated Exploration of Unknown Environments.
AB  - Over the last 20 years, a significant part of the research in exploratory
      robotics partially switches from looking for the most efficient way of exploring
      an unknown environment to finding what could motivate a robot to autonomously
      explore it. Moreover, a growing literature focuses not only on the topological
      description of a space (dimensions, obstacles, usable paths, etc.) but rather on
      more semantic components, such as multimodal objects present in it. In the search
      of designing robots that behave autonomously by embedding life-long learning
      abilities, the inclusion of mechanisms of attention is of importance. Indeed, be
      it endogenous or exogenous, attention constitutes a form of intrinsic motivation
      for it can trigger motor command toward specific stimuli, thus leading to an
      exploration of the space. The Head Turning Modulation model presented in this
      paper is composed of two modules providing a robot with two different forms of
      intrinsic motivations leading to triggering head movements toward audiovisual
      sources appearing in unknown environments. First, the Dynamic Weighting module
      implements a motivation by the concept of Congruence, a concept defined as an
      adaptive form of semantic saliency specific for each explored environment. Then,
      the Multimodal Fusion and Inference module implements a motivation by the
      reduction of Uncertainty through a self-supervised online learning algorithm that
      can autonomously determine local consistencies. One of the novelty of the
      proposed model is to solely rely on semantic inputs (namely audio and visual
      labels the sources belong to), in opposition to the traditional analysis of the
      low-level characteristics of the perceived data. Another contribution is found in
      the way the exploration is exploited to actively learn the relationship between
      the visual and auditory modalities. Importantly, the robot-endowed with binocular
      vision, binaural audition and a rotating head-does not have access to prior
      information about the different environments it will explore. Consequently, it
      will have to learn in real-time what audiovisual objects are of "importance" in
      order to rotate its head toward them. Results presented in this paper have been
      obtained in simulated environments as well as with a real robot in realistic
      experimental conditions.

PMID- 30297994
TI  - Causes of Performance Degradation in Non-invasive Electromyographic Pattern
      Recognition in Upper Limb Prostheses.
AB  - Surface Electromyography (EMG)-based pattern recognition methods have been
      investigated over the past years as a means of controlling upper limb prostheses.
      Despite the very good reported performance of myoelectric controlled prosthetic
      hands in lab conditions, real-time performance in everyday life conditions is not
      as robust and reliable, explaining the limited clinical use of pattern
      recognition control. The main reason behind the instability of myoelectric
      pattern recognition control is that EMG signals are non-stationary in real-life
      environments and present a lot of variability over time and across subjects,
      hence affecting the system's performance. This can be the result of one or many
      combined changes, such as muscle fatigue, electrode displacement, difference in
      arm posture, user adaptation on the device over time and inter-subject
      singularity. In this paper an extensive literature review is performed to present
      the causes of the drift of EMG signals, ways of detecting them and possible
      techniques to counteract for their effects in the application of upper limb
      prostheses. The suggested techniques are organized in a table that can be used to
      recognize possible problems in the clinical application of EMG-based pattern
      recognition methods for upper limb prosthesis applications and state-of-the-art
      methods to deal with such problems.

PMID- 30297996
TI  - Dopamine Receptor Activation Is Required for GABAergic Spike Timing-Dependent
      Plasticity in Response to Complex Spike Pairing in the Ventral Tegmental Area.
AB  - One of the most influential synaptic learning rules explored in the past decades
      is activity dependent spike-timing-dependent plasticity (STDP). In STDP, synapses
      are either potentiated or depressed based on the order of pre- and postsynaptic
      neuronal activation within narrow, milliseconds-long, time intervals. STDP is
      subject to neuromodulation by dopamine (DA), a potent neurotransmitter that
      significantly impacts synaptic plasticity and reward-related behavioral learning.
      Previously, we demonstrated that GABAergic synapses onto ventral tegmental area
      (VTA) DA neurons are able to express STDP (Kodangattil et al., 2013), however it
      is still unclear whether DA modulates inhibitory STDP in the VTA. Here, we used
      whole-cell recordings in rat midbrain slices to investigate whether DA D1-like
      and/or D2-like receptor (D1R/D2R) activation is required for induction of STDP in
      response to a complex pattern of spiking. We found that VTA but not Substantia
      nigra pars compact (SNc) DA neurons exhibit long-term depression (LTDGABA) in
      response to a combination of positive (pre-post) and negative (post-pre) timing
      of spiking (a complex STDP protocol). Blockade of either D1Rs or D2Rs prevented
      the induction of LTDGABA while activation of D1Rs did not affect the plasticity
      in response to this complex STDP protocol in VTA DA neurons.Our data suggest that
      this DA-dependent GABAergic STDP is selectively expressed at GABAergic synapses
      onto VTA DA neurons which could be targeted by drugs of abuse to mediate drug
      induced modulation of DA signaling within the VTA, as well as in VTA-projection
      areas, thereby affecting reward-related learning and drug-associated memories.

PMID- 30297997
TI  - The Combination of Functional and Structural MRI Is a Potential Screening Tool in
      Alzheimer's Disease.
AB  - Introduction: This study aimed to survey the discrimination power of parameters
      from cerebrospinal fluid (CSF) biomarkers, fluorodeoxyglucose uptake on PET (FDG
      PET), structural magnetic resonance imaging (MRI), and functional MRI in high-
      and low-risk subjects or in converters and stable subjects of normal and mild
      cognitive impairment (MCI) statuses. Methods: We used baseline resting-state
      functional MRI (rfMRI) from the Alzheimer's Disease Neuroimaging Initiative
      (ADNI) dataset to analyze functional networks and recorded subjects'
      characteristics and results of the CSF study, FDG-PET, and structural MRI from
      the ADNI website. All parameters were evaluated based on the between-group
      difference among normal (NC), MCI, and Alzheimer's disease (AD) groups. The
      parameters other than CSF results were included to study the difference between
      high- and low-AD-risk subjects in NC or MCI groups, based on CSF results. On the
      basis of two-year follow-up conditions, all parameters were compared between
      stable subjects and converters in NC and MCI. Results: CSF biomarkers, FDG-PET,
      structural MRI, and functional MRI are all able to differentiate AD from MCI or
      NC but not between MCI and NC. As compared with low-AD-risk subjects, high-risk
      subjects present decreased FDG-PET in both MCI and NC groups but structural MRI
      change only in MCI status and rfMRI alteration only in NC status. As compared
      with stable subjects, converters have decreased FDG-PET, functional network
      changes, and structural changes in both MCI and NC groups. Conclusion: The
      combination of functional and structural MRI is a safer screening tool but with
      similar power as FDG-PET to reflect CSF change in the AD pathological process and
      to identify high-risk subjects and converters in NC and MCI.

PMID- 30297998
TI  - Age Influences Microglial Activation After Cuprizone-Induced Demyelination.
AB  - Multiple sclerosis (MS) is a chronic inflammatory CNS disease, which causes
      demyelinated lesions and damages white and gray matter regions. Aging is a
      significant factor in the progression of MS, and microglia, the immune cells of
      the CNS tissue, play an important role in all disease stages. During aging,
      microglia are functionally altered. These age-related changes probably already
      begin early and might influence the progression of CNS pathologies. The aim of
      the present study was to investigate whether microglia in the middle-aged CNS
      already react differently to demyelination. For this purpose, several microglia
      markers (ionized calcium binding adaptor molecule 1 (Iba-1), P2RY12, F4/80, CD68,
      major histocompatibility complex II (MHCII), macrophage receptor with collagenous
      structure (Marco), Translocator protein 18 kD (TSPO), CD206, and CD163) were
      analyzed in the acute cuprizone demyelination model in young (2-month-old) and
      middle-aged (10-month-old) mice. In addition, microglial proliferation was
      quantified using double-labeling with proliferating cell nuclear antigen (PCNA)
      and bromodeoxyuridine (BrdU), which was injected with the onset of remyelination.
      To compare age-related microglial changes during de- and remyelination in both
      gray and white matter, the hilus of the dorsal hippocampal dentate gyrus (DG) and
      the splenium of the corpus callosum (CC) were analyzed in parallel. Age-related
      changes in microglia of healthy controls were more pronounced in the analyzed
      gray matter region (higher levels of F4/80 and Marco as well as lower expression
      of CD68 in middle-aged mice). During de- and remyelination, a stronger increase
      of the microglial markers Iba-1, CD68 and TSPO was observed in the splenium of
      the younger groups. There was a significant reduction of P2RY12 during
      demyelination, however, this was age- and region-dependent. The induction of the
      anti-inflammatory markers CD206 and CD163 was stronger in the middle-aged group,
      but also differed between the two analyzed regions. De- and remyelination led to
      a significant increase in PCNA+ microglia only in young groups within the white
      matter region. The number of BrdU+ microglia was not changed during de- or
      remyelination. These results clearly show that microglia are already altered
      during middle-age and also react differently to CNS demyelination, however, this
      is highly region-dependent.

PMID- 30297999
TI  - Astrocyte Activation and the Calcineurin/NFAT Pathway in Cerebrovascular Disease.
AB  - Calcineurin (CN) is a Ca2+/calmodulin-dependent protein phosphatase with high
      abundance in nervous tissue. Though enriched in neurons, CN can become strongly
      induced in subsets of activated astrocytes under different pathological
      conditions where it interacts extensively with the nuclear factor of activated T
      cells (NFATs). Recent work has shown that regions of small vessel damage are
      associated with the upregulation of a proteolized, highly active form of CN in
      nearby astrocytes, suggesting a link between the CN/NFAT pathway and chronic
      cerebrovascular disease. In this Mini Review article, we discuss CN/NFAT
      signaling properties in the context of vascular disease and use previous cell
      type-specific intervention studies in Alzheimer's disease and traumatic brain
      injury models as a framework to understand how astrocytic CN/NFATs may couple
      vascular pathology to neurodegeneration and cognitive loss.

PMID- 30298000
TI  - Drynaria fortunei Promoted Angiogenesis Associated With Modified MMP-2/TIMP-2
      Balance and Activation of VEGF Ligand/Receptors Expression.
AB  - Background and Purpose: Drynaria fortunei J. Sm (D. fortunei), known as Gu-Sui
      Bu, is used in traditional Chinese medicine to treat common injuries, including
      bone fractures and bruising. The specific functional mechanisms of the angiogenic
      and endothelial cell migration properties of D. fortunei are currently unclear.
      Thus, the purpose of this study is to validate the potential angiogenic and
      cellular migration properties and related mechanisms by D. fortunei both in vivo
      and in vitro. Experimental Approach: The present study investigates, both in vivo
      and in vitro, the wound healing effects of D. fortunei as associated with
      angiogenesis, specifically by the modulation of matrix metalloproteinases (MMPs)
      and upregulation of vascular endothelial growth factor (VEGF) ligand/receptors.
      In order to determine the potential angiogenic effects of D. fortunei, in vivo
      neovascularization of chick chorioallantoic membranes (CAMs) assay, and directed
      in vivo angiogenesis assay (DIVVA) were performed, while in vitro scratch wound
      healing, migration, and matrix-induced tube formation assays were performed by
      using human umbilical vascular endothelial cells (HUVECs). Furthermore, we used
      qPCR to analyze the gene expressions and Western blot to observe protein
      expressions of MMP-2, MMP-14, TIMP-2, RECK, and VEGF/VEGFRs. Results: This study
      identified five major compounds from the water extract of D. fortunei:
      protocatechuic acid, caffeic acid 4-O-beta-D-glucopyranoside, 5,7
      dihydroxychromone-7-O-rutinoside, neoeriocitrin, and naringin. D. fortunei was
      confirmed to activate in vivo angiogenesis by CAM and DIVVA assays. D. fortunei
      further exhibited in vitro angiogenic effects associated with cell migration, as
      demonstrated by the tube formation assay, transwell migration assay, and scratch
      wound healing assay. The extracellular MMP-2 activity was found to be dose
      dependently augmented both in vitro and in vivo by D. fortunei. The mRNA and
      protein expressions of MMP-2, and MMP-14 were increased; while the tissue
      inhibitor metalloproteinase-2 (TIMP-2), and reversion-inducing cysteine-rich
      protein with kazal motifs (RECK) were both decreased. Furthermore, D. fortunei
      activated the gene and protein expressions of VEGF-A, -B, and VEGFR-2, -3.
      Conclusion: D. fortunei increased MMP-2 activity, thereby stimulating
      angiogenesis and cell migration, both in vivo and in vitro, as a result of MMP-2
      and TIMP-2 balance modulation and the activation of VEGF/VEGFRs expression.

PMID- 30298001
TI  - Evaluation of Chitosan Derivative Microparticles Encapsulating Superparamagnetic
      Iron Oxide and Doxorubicin as a pH-Sensitive Delivery Carrier in Hepatic
      Carcinoma Treatment: An in vitro Comparison Study.
AB  - We developed a novel, pH-sensitive drug delivery microparticle based on N
      palmitoyl chitosan (NPCS) to transport the superparamagnetic iron oxide (SPIO)
      and anticancer drug doxorubicin (DOX). The characteristics of NPCS were
      characterized through nuclear magnetic resonance. Our results based on testing of
      volume swelling in multiple pH aqueous solutions revealed that the modified
      chitosan had a pH-sensitive property. The morphology and size of the DOX
      SPIO/NPCS microparticles were investigated using transmission electron microscopy
      and scanning electron microscopy. The statistical result of microparticles had
      diameter of 185 +/- 87 nm. Surface chemical moieties of DOX-SPIO/NPCS
      microparticles were confirmed using attenuated total reflection Fourier transform
      infrared spectroscopy and indicated the existence of mostly hydrophilic groups
      such as -OH, -C=O, and -C-O-C-. Transmission electron microscopy revealed the
      dark contrast of SPIO dots encapsulated in the NPCS matrix. Nuclear magnetic
      resonance T2-weighted magnetic resonance imaging confirmed that the produced DOX
      SPIO/NPCS microparticles still exhibited T2 relaxation durations as short as
      37.68 +/- 8.69 ms (under administration of 2.5 MUg/mL), which is comparable to
      the clinically required dosage. In the drug release profile, the DOX-SPIO/NPCS
      drug delivery microparticle was accelerated in an acidic environment (pH 6.5)
      compared with that in a basic environment. Microparticles in a cytotoxicity assay
      (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay) revealed
      that DOX-SPIO/NPCS microparticles had better antitumor ability than did free-form
      of DOX. Additionally, microparticles loaded with 0.5-5 MUg/mL DOX in an acidic
      environment (pH 6.5) demonstrated higher efficacy against Hep G2 cell growth,
      possibly because of the swelling effect of NPCS, resulting in volume expansion
      and easy drug release. Accordingly, these large DOX-SPIO/NPCS microparticles
      showed potential for application as a pH-sensitive drug delivery system and as
      chemoembolization particles for hepatic carcinoma therapy.

PMID- 30298002
TI  - Maprotiline Prevents Monocrotaline-Induced Pulmonary Arterial Hypertension in
      Rats.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease caused by
      increased pulmonary artery pressure and pulmonary vascular resistance, eventually
      leading to right heart failure until death. Soluble guanylate cyclase (sGC) has
      been regarded as an attractive drug target in treating PAH. In this study, we
      discovered that maprotiline, a tetracyclic antidepressant, bound to the full
      length recombinant sGC with a high affinity (K D = 0.307 MUM). Further study
      demonstrated that maprotiline concentration-dependently inhibited the
      proliferation of hypoxia-induced human pulmonary artery smooth muscle cells.
      Moreover, in a monocrotaline (MCT) rat model of PAH, maprotiline (ip, 10 mg/kg
      once daily) reduced pulmonary hypertension, inhibited the development of right
      ventricular hypertrophy and pathological changes of the pulmonary vascular
      remodeling. Taken together, our studies showed that maprotiline may contribute to
      attenuate disease progression of pulmonary hypertension.

PMID- 30298004
TI  - Pharmaceutical Care Increases Time in Therapeutic Range of Patients With Poor
      Quality of Anticoagulation With Warfarin.
AB  - Thromboembolic events are associated with high mortality and morbidity indexes.
      In this context, warfarin is the most widely prescribed oral anticoagulant agent
      for preventing and treating these events. This medication has a narrow
      therapeutic range and, consequently, patients usually have difficulty in
      achieving and maintaining stable target therapeutics. Some studies on the
      literature about oral anticoagulant management showed that pharmacists could
      improve the efficiency of anticoagulant therapy. However, the majority of these
      studies included general patients retrospectively. The aim of this study was to
      prospectively evaluate a pharmacist's warfarin management in patients with poor
      quality of anticoagulation therapy (Time in the Therapeutic Range- TTR < 50%). We
      included 268 patients with atrial fibrillation (AF) and without stable dose of
      warfarin (TTR < 50%, based on the last three values of International Normalized
      Ratio-INR). We followed them up for 12 weeks, INR values were evaluated and, when
      necessary, the dose adjustments were performed. During the first four visits,
      patient's INR was measured every 7 days. Then, if INR was within the target
      therapeutic range (INR: 2-3), the patient was asked to return in 30 days.
      However, if INR was out the therapeutic target, the patient was asked to return
      in 7 days. Adherence evaluation was measured through questionnaires and by
      counting the pills taken. Comparison between basal TTR (which was calculated
      based on the three last INR values before prospective phase) and TTR of 4 weeks
      (calculated by considering the INR tests from visits 0 to 4, in the prospective
      phase of the study) and basal TTR and TTR of 12 weeks (calculated based on the
      INR tests from visits 0 to 12, in the prospective phase of the study) revealed
      significant statistical differences (0.144 +/- 0.010 vs. 0.382 +/- 0.016; and
      0.144 +/- 0.010 vs. 0.543 +/- 0.014, p < 0.001, respectively). We also observed
      that the mean TTR of 1 year before (retrospective phase) was lower than TTR value
      after 12 weeks of pharmacist-driven treatment (prospective phase) (0.320 +/-
      0.015; 0.540 +/- 0.015, p < 0.001). In conclusion, pharmaceutical care was able
      to improve TTR values in patients with AF and poor quality of anticoagulation
      with warfarin.

PMID- 30298003
TI  - Chick Embryo: A Preclinical Model for Understanding Ischemia-Reperfusion
      Mechanism.
AB  - Ischemia-reperfusion (I/R)-related disorders, such as stroke, myocardial
      infarction, and peripheral vascular disease, are among the most frequent causes
      of disease and death. Tissue injury or death may result from the initial ischemic
      insult, primarily determined by the magnitude and duration of the interruption in
      blood supply and then by the subsequent reperfusion-induced damage. Various in
      vitro and in vivo models are currently available to study I/R mechanism in the
      brain and other tissues. However, thus far, no in ovo I/R model has been reported
      for understanding the I/R mechanisms and for faster drug screening. Here, we
      developed an in ovo Hook model of I/R by occluding and releasing the right
      vitelline artery of a chick embryo at 72 h of development. To validate the model
      and elucidate various underlying survival and death mechanisms, we employed
      imaging (Doppler blood flow imaging), biochemical, and blotting techniques and
      evaluated the cell death mechanism: autophagy and inflammation caused by I/R. In
      conclusion, the present model is useful in parallel with established in vitro and
      in vivo I/R models to understand the mechanisms of I/R development and its
      treatment.

PMID- 30298005
TI  - Effects of Valproic Acid on Cerebral Nutrient Carriers' Expression in the Rat.
AB  - Objective: The antiepileptic drug valproate has been shown to affect the
      expression of carriers for essential compounds and drugs in extracerebral
      tissues. The aim of the current study was to evaluate in vivo the effect of
      valproate treatment on the cerebral expression of carriers and selected genes of
      the blood-brain barrier (BBB) in the rat. Methods: Male Wistar rats were treated
      daily for 7 days by intraperitoneal injections of valproate (75, 150, or 300
      mg/kg/day) or the vehicle. mRNA was isolated from the cerebral cortex and the
      hippocampus. Transcript levels of 37 genes were measured using a customized gene
      expression assay. Quantitative histone acetylation was evaluated by western
      blotting. Glucose6-phosphate (G6P) tissue levels were used as a surrogate of
      cerebral glucose concentrations. Results: Valproate treatment was associated with
      significant reduction (up to 22%; P < 0.05) in cortical and hippocampal claudin 5
      normalized Slc2a1 (Glut1) mRNA expression. G6P levels were not significantly
      altered, but were correlated with Slc2a1 transcript levels (r = 0.499; P < 0.02).
      None of the other 36 screened genes were significantly affected by valproate.
      Cortical histone hyperacetylation indicated cerebral activity of valproate on a
      major pathway regulating gene expression (P < 0.02). Significance: The effect of
      valproate on nutrient carriers appears to be tissue-specific and even brain area
      specific. If validated in humans, the changes in Glut1 expression might have
      clinical implications in positron emission tomography (PET) imaging. Further
      studies are required for elucidating the relevance of these findings to the
      clinic.

PMID- 30298006
TI  - Luteolin Inhibits Vascular Smooth Muscle Cell Proliferation and Migration by
      Inhibiting TGFBR1 Signaling.
AB  - Vascular smooth muscle cell (VSMC) proliferation and migration play a critical
      role in the development of arterial remodeling during various vascular diseases
      including atherosclerosis, hypertension, and related diseases. Luteolin is a food
      derived flavonoid that exerts protective effects on cardiovascular diseases.
      Here, we investigated whether transforming growth factor-beta receptor 1 (TGFBR1)
      signaling underlies the inhibitory effects of luteolin on VSMC proliferation and
      migration. We found that luteolin reduced the proliferation and migration of
      VSMCs, specifically A7r5 and HASMC cells, in a dose-dependent manner, based on
      MTS and EdU, and Transwell and wound healing assays, respectively. We also
      demonstrated that it inhibited the expression of proliferation-related proteins
      including PCNA and Cyclin D1, as well as the migration-related proteins MMP2 and
      MMP9, in a dose-dependent manner by western blotting. In addition, luteolin dose
      dependently inhibited the phosphorylation of TGFBR1, Smad2, and Smad3. Notably,
      adenovirus-mediated overexpression of TGFBR1 enhanced TGFBR1, Smad2, and Smad3
      activation in VSMCs and partially blocked the inhibitory effect of luteolin on
      TGFBR1, Smad2, and Smad3. Moreover, overexpression of TGFBR1 rescued the
      inhibitory effects of luteolin on the proliferation and migration of VSMCs.
      Additionally, molecular docking showed that this compound could dock onto an
      agonist binding site of TGFBR1, and that the binding energy between luteolin and
      TGFBR1 was -10.194 kcal/mol. Simulations of molecular dynamics showed that TGFBR1
      luteolin binding was stable. Collectively, these data demonstrated that luteolin
      might inhibit VSMC proliferation and migration by suppressing TGFBR1 signaling.

PMID- 30298007
TI  - So-Cheong-Ryoung-Tang Attenuates Pulmonary Inflammation Induced by Cigarette
      Smoke in Bronchial Epithelial Cells and Experimental Mice.
AB  - So-Cheong-Ryoung-Tang is a traditionally used herbal formula for the treatment of
      pulmonary diseases in China, Korea, and Japan. We investigated the protective
      effects of So-Cheong-Ryong-Tang water extract (SCWE) in cigarette smoke
      concentrate (CSC) stimulated human airway epithelial cell line NCI-H292 and mice
      exposed cigarette smoke (CS) and lipopolysaccharide (LPS). In the CSC-stimulated
      NCI-H292 cells, SCWE inhibited proinflammatory cytokines in a concentration
      dependent manner, as evidenced by a reduction in their mRNA levels. Also, SCWE
      significant reduced inducible nitric oxide synthase (iNOS) expression and nuclear
      factor kappa B (NF-kappaB) phosphorylation in CSC-stimulated cells. The mice were
      exposed to CS for 1 h per day (a total of eight cigarettes per day) for 7 days
      and received LPS intranasally on day 5. The mice were administered a dose of SCWE
      (100 and 200 mg/kg) 1 h before CS exposure. In in vivo, SCWE decreased the
      inflammatory cell count and reduced the expression of the proinflammatory
      cytokines in the broncho-alveolar lavage fluid (BALF) compared with CS and LPS
      exposed mice. SCWE attenuated inflammatory cell infiltration in airway induced by
      CS and LPS exposure, and this decrease was accompanied by a reduction in the
      expression levels of iNOS and MMP-9 in lung tissue. The extract also inhibited
      the phosphorylation of inhibitor of kappa B alpha (IkappaBalpha) and NF-kappaB
      induced by CS and LPS exposure in lung tissue. These results suggest that SCWE
      may effectively inhibit airway inflammatory responses induced by CS and LPS
      exposure via the NF-kappaB pathway. Therefore, SCWE may be a potential treatment
      for airway inflammatory diseases, such as chronic obstructive pulmonary disease
      (COPD).

PMID- 30298009
TI  - Cucurbitacin B Induces Hypoglycemic Effect in Diabetic Mice by Regulation of AMP
      Activated Protein Kinase Alpha and Glucagon-Like Peptide-1 via Bitter Taste
      Receptor Signaling.
AB  - Taste receptors exist in several organs from tongue to colon and have diverse
      functions dependent on specific cell type. In enteroendocrine L-cells,
      stimulation of taste receptor signaling induces incretin hormones. Among incretin
      hormones, glucagon-like peptide-1 (GLP-1) induces insulinotropic action by
      activating GLP-1 receptor of pancreatic beta-cells. However, GLP-1 mimetic
      medicines have reported clinical side effects, such as autoimmune hepatitis,
      acute kidney injury, pancreatitis, and pancreatic cancer. Here, we hypothesized
      that if natural components in ethnomedicines can activate agonistic action of
      taste receptor; they may stimulate GLP-1 and therefore, could be developed as
      safe and applicable medicines to type 2 diabetes mellitus (T2DM) with minimal
      side effects. Cucurbitacin B (CuB) is composed of triterpenoid structure and its
      structural character, that represents bitterness, can stimulate AMP-activated
      protein kinase (AMPK) pathway. CuB ameliorated hyperglycemia by activating
      intestinal AMPK levels and by inducing plasma GLP-1 and insulin release in
      diabetic mice. This hypoglycemic action was decreased in dorsomorphin-injected
      mice and alpha-gustducin null mice. Moreover, systemic inhibition study in
      differentiated NCI-H716 cell line showed that CuB-mediated GLP-1 secretion was
      involved in activation of AMPK through alpha-gustducin and Gbetagamma-signaling
      of taste receptors. In summary, we conclude that, CuB represents novel
      hypoglycemic agents by activation of AMPK and stimulation of GLP-1 in
      differentiated enteroendocrine L-cells. These results suggest that taste receptor
      signaling-based therapeutic agents within tremendously diverse ethnomedicines,
      could be applied to developing therapeutics for T2DM patients.

PMID- 30298010
TI  - Development and Role in Therapy of Canakinumab in Adult-Onset Still's Disease.
AB  - Adult-onset Still's disease (AOSD) is a rare inflammatory disease of unknown
      etiology typically characterized by episodes of spiking fever, evanescent rash,
      arthralgia, leukocytosis, and hyperferritinemia. The pivotal role of interleukin
      (IL)-1 and other pro-inflammatory cytokines gives rise to the development of new
      targeted therapies. Currently, AOSD patients can benefit from efficient and well
      tolerated biologic agents, such as IL-1, IL-6, and tumour necrosis factor (TNF)
      alpha antagonists. Canakinumab, a human monoclonal anti-IL-1beta antibody, is
      indicated for the treatment of different autoinflammatory syndromes in adults,
      adolescents, and children and it has recently been approved for AOSD treatment.
      In this article, we summarize the structural and biochemical data describing the
      molecular interactions between Canakinumab and its target antigen. Some special
      considerations of the pharmacological properties of Canakinumab are included. We
      also review the safety, efficacy and tolerability of this drug for the treatment
      of AOSD.

PMID- 30298011
TI  - Generation of MicroRNA-34 Sponges and Tough Decoys for the Heart: Developments
      and Challenges.
AB  - Heart failure (HF) is a debilitating and deadly chronic disease, with almost 50%
      of patients with HF dying within 5 years of diagnosis. With limited effective
      therapies to treat or cure HF, new therapies are greatly needed. microRNAs
      (miRNAs) are small non-coding RNA molecules that are powerful regulators of gene
      expression and play a key role in almost every biological process. Disruptions in
      miRNA gene expression has been functionally linked to numerous diseases,
      including cardiovascular disease. Molecular tools for manipulating miRNA activity
      have been developed, and there is evidence from preclinical studies demonstrating
      the potential of miRNAs to be therapeutic targets for cardiovascular disease. For
      clinical application, miRNA sponges and tough decoys have been developed for more
      stable suppression and targeted delivery of the miRNA of choice. The aim of this
      study was to generate miRNA sponges and tough decoys to target miR-34 in the
      mouse heart. We present data to show that using both approaches we were unable to
      get significant knockdown of miR-34 or regulate miR-34 target genes in the heart
      in vivo. We also review recent applications of this method in the heart and
      discuss further considerations for optimisation in construct design and testing,
      and the obstacles to be overcome before they enter the clinic.

PMID- 30298012
TI  - A Computational Framework to Benchmark Basket Catheter Guided Ablation in Atrial
      Fibrillation.
AB  - Catheter ablation is a curative therapeutic approach for atrial fibrillation
      (AF). Ablation of rotational sources based on basket catheter measurements has
      been proposed as a promising approach in patients with persistent AF to
      complement pulmonary vein isolation. However, clinically reported success rates
      are equivocal calling for a mechanistic investigation under controlled
      conditions. We present a computational framework to benchmark ablation strategies
      considering the whole cycle from excitation propagation to electrogram
      acquisition and processing to virtual therapy. Fibrillation was induced in a
      patient-specific 3D volumetric model of the left atrium, which was homogeneously
      remodeled to sustain reentry. The resulting extracellular potential field was
      sampled using models of grid catheters as well as realistically deformed basket
      catheters considering the specific atrial anatomy. The virtual electrograms were
      processed to compute phase singularity density maps to target rotor tips with up
      to three circular ablations. Stable rotors were successfully induced in different
      regions of the homogeneously remodeled atrium showing that rotors are not
      constrained to unique anatomical structures or locations. Density maps of rotor
      tip trajectories correctly identified and located the rotors (deviation < 10 mm)
      based on catheter recordings only for sufficient resolution (inter-electrode
      distance <=3 mm) and proximity to the wall (<=10 mm). Targeting rotor sites with
      ablation did not stop reentries in the homogeneously remodeled atria independent
      from lesion size (1-7 mm radius), from linearly connecting lesions with
      anatomical obstacles, and from the number of rotors targeted sequentially (<=3).
      Our results show that phase maps derived from intracardiac electrograms can be a
      powerful tool to map atrial activation patterns, yet they can also be misleading
      due to inaccurate localization of the rotor tip depending on electrode resolution
      and distance to the wall. This should be considered to avoid ablating regions
      that are in fact free of rotor sources of AF. In our experience, ablation of
      rotor sites was not successful to stop fibrillation. Our comprehensive simulation
      framework provides the means to holistically benchmark ablation strategies in
      silico under consideration of all steps involved in electrogram-based therapy
      and, in future, could be used to study more heterogeneously remodeled disease
      states as well.

PMID- 30298008
TI  - Hydrogen Sulfide (H2S)-Releasing Compounds: Therapeutic Potential in
      Cardiovascular Diseases.
AB  - Cardiovascular disease is the main cause of death worldwide, but its pathogenesis
      is not yet clear. Hydrogen sulfide (H2S) is considered to be the third most
      important endogenous gasotransmitter in the organism after carbon monoxide and
      nitric oxide. It can be synthesized in mammalian tissues and can freely cross the
      cell membrane and exert many biological effects in various systems including
      cardiovascular system. More and more recent studies have supported the protective
      effects of endogenous H2S and exogenous H2S-releasing compounds (such as NaHS,
      Na2S, and GYY4137) in cardiovascular diseases, such as cardiac hypertrophy, heart
      failure, ischemia/reperfusion injury, and atherosclerosis. Here, we provided an
      up-to-date overview of the mechanistic actions of H2S as well as the therapeutic
      potential of various classes of H2S donors in treating cardiovascular diseases.

PMID- 30298013
TI  - O-GlcNAc Modification During Pregnancy: Focus on Placental Environment.
AB  - Successful placentation is a key event for fetal development, which commences
      following embryo implantation into the uterine wall, eliciting decidualization,
      placentation, and remodeling of blood vessels to provide physiological exchange
      between embryo-fetus and mother. Several signaling pathways are recruited to
      modulate such important processes and specific proteins that regulate placental
      function are a target for the glycosylation with O-linked beta-N
      acetylglucosamine (O-GlcNAc), or O-GlcNAcylation. This is a reversible post
      translational modification on nuclear and cytoplasmic proteins, mainly controlled
      by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). O-GlcNAcylation has been
      implicated as a modulator of proteins, both in physiological and pathological
      conditions and, more recently, O-GlcNAc has also been shown to be an important
      modulator in placental tissue. In this mini-review, the interplay between O
      GlcNAcylation of proteins and placental function will be addressed, discussing
      the possible implications of this post-translational modification through
      placental development and pregnancy.

PMID- 30298015
TI  - The Validity and Between-Unit Variability of GNSS Units (STATSports Apex 10 and
      18 Hz) for Measuring Distance and Peak Speed in Team Sports.
AB  - The aims of this study were (i) to investigate the criterion validity (vs. gold
      standard measurements) of the 10 and 18 Hz STATSports Apex units for measuring
      distances and peak speed (Vpeak) outcomes and (ii) to investigate the between
      unit variability. Twenty university students were enrolled in the study (age 21
      +/- 2 years, weight 72 +/- 6 kg, and height 1.76 +/- 0.05 m). The criterion
      validity was tested by comparing the distances recorded by the units with ground
      truth reference (400-m trial, 128.5-m circuit, and 20-m trial). Vpeak values were
      compared with those determined by a gold standard criterion device (Stalker ATS
      Radar Gun) during a linear 20-m sprint. The distance biases for the Apex 10 Hz in
      the 400-m trial, 128.5-m circuit, and 20-m trial were 1.05 +/- 0.87%, 2.3 +/-
      1.1%, and 1.11 +/- 0.99%, respectively, while for the Apex 18 Hz the biases were
      1.17 +/- 0.73%, 2.11 +/- 1.06%, and 1.15 +/- 1.23%, respectively. Vpeak measured
      by the Apex 10 and 18 Hz were 26.5 +/- 2.3 km h-1 and 26.5 +/- 2.6 km h-1,
      respectively, with the criterion method reporting 26.3 +/- 2.4 km h-1, with a
      bias of 2.36 +/- 1.67% and 2.02 +/- 1.24%, respectively. This study is the first
      to validate and compare the STATSports Apex 10 and 18 Hz. Between-analysis (t
      test) for total distance and Vpeak reported non-significant differences. Apex
      units reported a small error of around 1-2% compared to the criterion distances
      during 400-m, 128.5-m circuit, 20-m trials, and Vpeak. In conclusion, both units
      could be used with confidence to measure these variables during training and
      match play.

PMID- 30298014
TI  - Relationship Between Morning Heart Rate Variability and Creatine Kinase Response
      During Intensified Training in Recreational Endurance Athletes.
AB  - Specific physiological responses and their relationship were analyzed in 12
      recreational endurance athletes (43.8 +/- 7.9 years) during a period of
      intensified cycling training. Heart rate (HR), HR variability (HRV), serum
      creatine kinase (S-CK) and haematocrit (Hct) were measured in the mornings before
      (PRE) and following three consecutive days of intensified training (POST 1-3).
      Morning HR increased during this period (PRE: 52.2 +/- 6.7 bpm, POST 1: 58.8 +/-
      7.0 bpm, POST 2: 58.5 +/- 8.1 bpm, POST 3: 57.9 +/- 7.2 bpm; F(3,33) = 11.182, p
      < 0.001, etap 2 = 0.554). Parasympathetic HRV indices decreased from PRE to POST
      (F(3,33) >= 11.588, p < 0.001, etap 2 >= 0.563), no effect was found for
      sympathetically modulated HRV (F(3,33) = 2.287, p = 0.101, etap 2 = 0.203). Hct
      decreased (PRE: 49.9 +/- 4.0%, POST 1: 46.5 +/- 5.1%, POST 2: 45.5 +/- 3.8%, POST
      3: 43.2 +/- 3.4%; F(3,33) = 11.909, p < 0.001, etap 2 = 0.520) and S-CK increased
      during the training period (PRE: 90.0 +/- 32.1 U/L, POST 1: 334.7 +/- 487.6 U/L,
      POST 2: 260.1 +/- 303.4 U/L, POST 3: 225.1 +/- 258.8 U/L; F(3,33) = 3.996, p =
      0.017, etap 2 = 0.285). S-CK release was associated with HR (r = 0.453, p =
      0.002, n = 44), RMSSD (r = -0.494, p = 0.001, n = 44) and HF-Power (r = -0.490, p
      = 0.001, n = 44). A period of intensified training was associated with
      haemodilution, parasympathetic withdrawal and S-CK-increase. Cardiac autonomic
      control at morning rest correlated with the S-CK-release; and thus, may serve as
      a practical mean to complementary monitor and prescribe training load in this
      population.

PMID- 30298016
TI  - The Influence of MicroRNAs on Mitochondrial Calcium.
AB  - Abnormal mitochondrial calcium ([Ca2+]m) handling and energy deficiency results
      in cellular dysfunction and cell death. Recent studies suggest that nuclear
      encoded microRNAs (miRNA) are able to translocate in to the mitochondrial
      compartment, and modulate mitochondrial activities, including [Ca2+]m uptake.
      Apart from this subset of miRNAs, there are several miRNAs that have been
      reported to target genes that play a role in maintaining [Ca2+]m levels in the
      cytoplasm. It is imperative to validate miRNAs that alter [Ca2+]m handling, and
      thereby alter cellular fate. The focus of this review is to highlight the
      mitochondrial miRNAs (MitomiRs), and other cytosolic miRNAs that target mRNAs
      which play an important role in [Ca2+]m handling.

PMID- 30298017
TI  - The Relation Between Capillary Transit Times and Hemoglobin Saturation
      Heterogeneity. Part 2: Capillary Networks.
AB  - Brain metabolism is highly dependent on continuous oxygen supply. Cortical
      microvascular networks exhibit heterogeneous blood flow, leading to non-uniform
      tissue oxygenation and capillary hemoglobin saturation. We recently proposed
      capillary outflow saturation heterogeneity (COSH) to represent effects of
      heterogeneity on oxygen supply to tissue regions most vulnerable to hypoxia, and
      showed that diffusive oxygen exchange among red blood cells within capillaries
      and among capillaries (diffusive interaction) significantly reduces COSH in
      simplified geometrical configurations. Here, numerical simulations of oxygen
      transport in capillary network geometries derived from mouse somatosensory cortex
      are presented. Diffusive interaction was found to reduce COSH by 41 to 62%
      compared to simulations where diffusive interaction was excluded. Hemoglobin
      saturation drop across the microvascular network is strongly correlated with red
      blood cell transit time, but the coefficient of variation of saturation drop is
      approximately one third lower. Unexpectedly, the radius of the tissue cylinder
      supplied by a capillary correlates weakly with the anatomical tissue cylinder
      radius, but strongly with hemoglobin saturation. Thus, diffusive interaction
      contributes greatly to the microcirculation's ability to achieve tissue
      oxygenation, despite heterogeneous capillary transit time and hematocrit
      distribution. These findings provide insight into the effects of cerebral small
      vessel disease on tissue oxygenation and brain function.

PMID- 30298018
TI  - Reducing Error in ECG Forward Simulations With Improved Source Sampling.
AB  - A continuing challenge in validating electrocardiographic imaging (ECGI) is the
      persistent error in the associated forward problem observed in experimental
      studies. One possible cause of this error is insufficient representation of the
      cardiac sources; cardiac source measurements often sample only the ventricular
      epicardium, ignoring the endocardium and the atria. We hypothesize that
      measurements that completely cover the pericardial surface are required for
      accurate forward solutions. In this study, we used simulated and measured cardiac
      potentials to test the effect of different levels of spatial source sampling on
      the forward simulation. Not surprisingly, increasing the source sampling over the
      atria reduced the average error of the forward simulations, but some sampling
      strategies were more effective than others. Uniform and random distributions of
      samples across the atrial surface were the most efficient strategies in terms of
      lowest error with the fewest sampling locations, whereas "single direction"
      strategies, i.e., adding to the atrioventricular (AV) plane or atrial roof only,
      were the least efficient. Complete sampling of the atria is needed to eliminate
      errors from missing cardiac sources, but while high density sampling that covers
      the entire atria yields the best results, adding as few as 11 electrodes on the
      atria can significantly reduce these errors. Future validation studies of the ECG
      forward simulations should use a cardiac source sampling that takes these
      considerations into account, which will, in turn, improve validation and
      understanding of ECGI.

PMID- 30298019
TI  - The Correlation Between Circulating Ghrelin and Insulin Resistance in Obesity: A
      Meta-Analysis.
AB  - Background: Ghrelin, a peptide mainly produced by stomach X-A cells. It plays a
      pivotal role in the regulation of food intake and energy metabolism, including
      glucose metabolism and insulin sensitivity. However, the correlation between
      circulating ghrelin levels and insulin resistance in obesity remained uncertain.
      This meta-analysis aimed to clarify the association between ghrelin and IR in
      obesity. Methods: A systematic literature search was performed using PubMed,
      EMBASE, Cochrane Library and Web of Science until April 18, 2018 with the
      keywords "ghrelin" and "insulin resistance." Two independent reviewers selected
      studies and assessed data. Subgroup analyses were performed to search for sources
      of heterogeneity. Funnel plots and Egger's test were used to detect publication
      bias. A random-effects model was used to calculate the pooled effect size.
      Results: Ten studies with 546 participants were included in this meta-analysis.
      We found that ghrelin levels were negatively correlated with IR in obese
      individuals. (r = -0.31; 95% CI: -0.45 to -0.18). Subgroup analysis revealed that
      circulating ghrelin levels were significantly negatively correlated with IR in
      people with normal fasting blood glucose (FBG) (<6.9 mmol/dl) (r = -0.28; 95% CI:
      -0.47 to -0.09, I 2 = 39.5%), while there was no relationship between circulating
      ghrelin levels and IR in the high FBG group (>6.9 mmol/dl) (r = -0.15; 95% CI: 
      0.33 to 0.03, I 2 = 0.0%). Publication bias was insignificant (Egger's test: P =
      0.425). Conclusion: In obesity, circulating ghrelin levels were significantly
      negative correlated with insulin resistance in individuals with normal fasting
      blood glucose.

PMID- 30298020
TI  - Fibrogenic Secretome of Sirtuin 1-Deficient Endothelial Cells: Wnt, Notch and
      Glycocalyx Rheostat.
AB  - Sirtuins (SIRT) are ubiquitous histone and protein deacetylases and a member of
      this family, SIRT1, is the best-studied one. Its functions in endothelial cells
      encompass branching angiogenesis, activation of endothelial nitric oxide
      synthase, regulation of proapoptotic and proinflammatory pathways, among others.
      Defective SIRT1 activity has been described in various cardiovascular, renal
      diseases and in aging-associated conditions. Therefore, understanding of SIRT1
      deficient, endothelial dysfunctional phenotype has much to offer clinically.
      Here, we summarize recent studies by several investigative teams of the
      characteristics of models of global endothelial SIRT1 deficiency, the causes of
      facilitative development of fibrosis in these conditions, dissect the protein
      composition of the aberrant secretome of SIRT1-deficient endothelial cells and
      present several components of this aberrant secretome that are involved in
      fibrogenesis via activation of fibroblasts to myofibroblasts. These include
      ligands of Wnt and Notch pathways, as well as proteolytic fragments of glycocalyx
      core protein, syndecan-4. The latter finding is crucial for understanding the
      degradation of glycocalyx that accompanies SIRT1 deficiency. This spectrum of
      abnormalities associated with SIRT1 deficiency in endothelial cells is essential
      for understanding the origins and features of endothelial dysfunction in a host
      of cardiovascular and renal diseases.

PMID- 30298021
TI  - Transcriptome Analysis Provides Insights Into the Adaptive Responses to Hypoxia
      of a Schizothoracine Fish (Gymnocypris eckloni).
AB  - The schizothoracine fish endemic to the Qinghai-Tibetan Plateau are comparatively
      well adapted to aquatic environments with low oxygen partial pressures. However,
      few studies have used transcriptomic profiling to investigate the adaptive
      responses of schizothoracine fish tissues to hypoxic stress. This study compared
      the transcriptomes of Gymnocypris eckloni subjected to 72 h of hypoxia (Dissolved
      oxygen, DO = 3.0 +/- 0.1 mg/L) to those of G. eckloni under normoxia (DO = 8.4 +/
      0.1 mg/L). To identify the potential genes and pathways activated in response to
      hypoxic stress, we collected muscle, liver, brain, heart, and blood samples from
      normoxic and hypoxic fish for RNA-Seq analysis. We annotated 337,481 gene
      fragments. Of these, 462 were differentially expressed in the hypoxic fish as
      compared to the normoxic fish. Under hypoxia, the transcriptomic profiles of the
      tissues differed, with muscle the most strongly affected by hypoxia. Our data
      indicated that G. eckloni underwent adaptive changes in gene expression in
      response to hypoxia. Several strategies used by G. eckloni to cope with hypoxia
      were similar to those used by other fish, including a switch from aerobic
      oxidation to anaerobic glycolysis and the suppression of major energy-requiring
      processes. However, G. eckloni used an additional distinct strategy to survive
      hypoxic environments: a strengthening of the antioxidant system and minimization
      of ischemic injury. Here, we identified several pathways and related genes
      involved in the hypoxic response of the schizothoracine fish. This study provides
      insights into the mechanisms used by schizothoracine fish to adapt to hypoxic
      environments.

PMID- 30298022
TI  - Psychiatric Disorders in Refugees and Internally Displaced Persons After Forced
      Displacement: A Systematic Review.
AB  - Background: Protracted armed conflicts not only shape political, legal, and socio
      economic structures, but also have a lasting impact on people's human migration.
      In 2017, the United Nations High Commissioner for Refugees reported an
      unprecedented number of 65.6 million individuals who were displaced worldwide as
      a result of armed conflicts. To date, however, little is known about these
      people's mental health status. Therefore, we conducted a systematic review of the
      prevalence of psychiatric disorders among forcibly displaced populations in
      settings of armed conflicts. Methods: We undertook a database search using
      Medline, PsycINFO, PILOTS, and the Cochrane Library, using the following keywords
      and their appropriate synonyms to identify relevant articles for possible
      inclusion: "mental health," "refugees," "internally displaced people," "survey,"
      and "war." This search was limited to original articles, systematic reviews, and
      meta-analyses published after 1980. We reviewed studies with prevalence rates of
      common psychiatric disorders-mood and anxiety disorders, psychotic disorders,
      personality disorders, substance abuse, and suicidality-among adult internally
      displaced persons (IDPs) and refugees afflicted by armed conflicts. Results: The
      search initially yielded 915 articles. Of these references 38 studies were
      eligible and provided data for a total of 39,518 adult IDPs and refugees from 21
      countries. The highest prevalence were for reported for post-traumatic stress
      disorder (3-88%), depression (5-80%), and anxiety disorders (1-81%) with large
      variation. Only 12 original articles reported about other mental disorders.
      Conclusions: These results show a substantial lack of data concerning the wider
      extent of psychiatric disability among people living in protracted displacement
      situations. Ambitious assessment programs are needed to support the
      implementation of sustainable global mental health policies in war-torn
      countries. Finally, there is an urgent need for large-scale interventions that
      address psychiatric disorders in refugees and internally displaced persons after
      displacement.

PMID- 30298024
TI  - Protocol for the REVISIT-BPD Trial, a Randomized Controlled Trial Testing the
      Effectiveness of an Internet-Based Self-Management Intervention in the Treatment
      of Borderline Personality Disorder (BPD).
AB  - Introduction: Borderline Personality Disorder (BPD) is a prevalent condition that
      is often under-treated. This is partly because very few psychotherapists offer
      treatment for this disabling disorder. Internet-based self-management
      interventions could contribute to reducing the treatment gap but-mainly due to
      safety concerns-these have never been tested for BPD in controlled trials.
      Methods: Patients with BPD will be recruited primarily via the internet and
      randomized to two groups: care as usual (CAU) alone) or the self-management
      intervention priovi(r) in addition to CAU. At the end of the diagnostic
      interview, all participants will discuss an emergency plan. The main outcome
      measure is the clinician-rated symptom severity using the BPD Severity Index
      (BPDSI). Secondary outcome measures include a range of self-reported scales, an
      SCID-diagnosis of BPD and several safety parameters including serious adverse
      events (e.g., a life-threatening event, hospitalization or suicide attempt).
      Discussion: This trial will evaluate the effectiveness of the self-management
      intervention, priovi, in reducing symptoms of BPD. It will also assess the safety
      of its use in this target population. If successful, this intervention would be
      the first comprehensive internet intervention for the treatment of BPD and
      complement the wide range of internet interventions effective in treating other
      mental disorders, particularly depression and anxiety disorders. Trial
      Registration: NCT03418142 (clinicaltrials.gov) on January 23rd 2018. Trial
      status: recruiting, currently N = 108 (July 2018).

PMID- 30298023
TI  - Putative Astroglial Dysfunction in Schizophrenia: A Meta-Analysis of 1H-MRS
      Studies of Medial Prefrontal Myo-Inositol.
AB  - Background: Several lines of evidence support a role for astroglial pathology in
      schizophrenia. Myo-inositol is particularly abundant in astroglia. Many small
      sized studies have reported on myo-inositol concentration in schizophrenia, but
      to date these have not been pooled to estimate a collective effect size. Methods:
      We reviewed all proton magnetic resonance spectroscopy (1H-MRS) studies reporting
      myo-inositol values for patients satisfying DSM or ICD based criteria for
      schizophrenia in comparison to a healthy controls group in the medial prefrontal
      cortex published until February 2018. A random-effects model was used to
      calculate the pooled effect size using metafor package. A meta-regression
      analysis of moderator variables was also undertaken. Results: The literature
      search identified 19 studies published with a total sample size of 585 controls,
      561 patients with schizophrenia. Patients with schizophrenia had significantly
      reduced medial prefrontal myo-inositol compared to controls (RFX standardized
      mean difference = 0.19, 95% CI [0.05-0.32], z = 2.72, p = 0.0067; heterogeneity p
      = 0.09). Studies with more female patients reported more notable schizophrenia
      related reduction in myo-inositol (z = 2.53, p = 0.011). Discussion: We report a
      small, but significant reduction in myo-inositol concentration in the medial
      prefrontal cortex in schizophrenia. The size of the reported effect indicates
      that the biological pathways affecting the astroglia are likely to operate only
      in a subset of patients with schizophrenia. MRS myo-inositol could be a useful
      tool to stratify and investigate such patients.

PMID- 30298025
TI  - Clinical Perspective on Passive Audio Vocal Measurement in the Evaluation of
      Selective Mutism.
AB  - Selective Mutism (SM) is an anxiety disorder often diagnosed in early childhood
      and characterized by persistent failure to speak in certain social situations but
      not others. Diagnosing SM and monitoring treatment response can be quite complex,
      due in part to changing definitions of and scarcity of research about the
      disorder. Subjective self-reports and parent/teacher interviews can complicate SM
      diagnosis and therapy, given that similar speech problems of etiologically
      heterogeneous origin can be attributed to SM. The present perspective discusses
      the potential for passive audio capture to help overcome psychiatry's current
      lack of objective and quantifiable assessments in the context of SM. We present
      supportive evidence from two pilot studies indicating the feasibility of using a
      digital wearable device to quantify child vocalization features affected by SM.
      We also highlight comparative analyses of passive audio capture and its potential
      to enhance diagnostic characterizations for SM, as well as possible limitations
      of such technologies.

PMID- 30298027
TI  - Use of Baclofen for Alcohol Use Disorders in the United States.

PMID- 30298026
TI  - Interoceptive Anxiety and Body Representation in Anorexia Nervosa.
AB  - Individuals with anorexia nervosa (AN) typically display anxious traits prior to
      the onset of food avoidance and weight loss that characterize the disorder. Meal
      associated anxiety is an especially common clinical feature in these patients,
      and heightened sensitivity to sympathetically mediated interoceptive sensations
      has also been observed. However, it remains unclear how heightened interoceptive
      sensitivity relates to experiences of anxiety before and after meals. To
      investigate this relationship, we experimentally induced anxiety and panic
      symptoms with isoproterenol, a peripheral sympathetic agonist similar to
      adrenaline, across several different conditions: during panic provocation, during
      anticipation of a 1,000 Calorie meal, and after meal consumption. Fifteen AN and
      15 age- and sex-matched healthy comparisons received bolus infusions of
      isoproterenol and saline in a double-blinded, randomized design. Participants
      rated anxiety symptoms after each infusion, completed panic rating scales, and
      traced the location of perceived palpitations on a manikin to index interoceptive
      "body map" representation. The AN group reported significantly elevated anxiety
      relative to healthy comparisons during infusions before and after the meal, but
      surprisingly, not during panic provocation. These symptoms were accompanied by
      geographical differences in patterns of perceived heartbeat sensations across
      each condition. In particular, the AN group localized heartbeat sensations
      disproportionately to the chest during meal related saline infusions, when no
      cardiorespiratory modulation actually occurred. The AN group also showed a trend
      toward higher panic attack rates during the meal anticipation period. Correcting
      for anxiety levels reported during saline infusions abolished group differences
      in anxiety change across all conditions, suggesting a significant contribution of
      anxious traits in AN. The observation of meal related "visceral illusions"
      provides further evidence that AN is associated with abnormal interoceptive
      representation of the heartbeat and suggests that meal consumption, particularly
      when anticipated, preferentially alters the processing of interoception related
      signals in AN.

PMID- 30298030
TI  - Dietary Behavior: An Interdisciplinary Conceptual Analysis and Taxonomy.
AB  - Background: Dietary behavior encompasses many aspects, terms for which are used
      inconsistently across different disciplines and research traditions. This hampers
      communication and comparison across disciplines and impedes the development of a
      cumulative science. We describe the conceptual analysis of the fuzzy umbrella
      concept "dietary behavior" and present the development of an interdisciplinary
      taxonomy of dietary behavior. Methods: A four-phase multi-method approach was
      employed. Input was provided by 76 scholars involved in an international research
      project focusing on the determinants of dietary behavior. Input was collected
      from the scholars via an online mind mapping procedure. After structuring,
      condensing, and categorizing this input into a compact taxonomy, the result was
      presented to all scholars, discussed extensively, and adapted. A second revision
      round was then conducted among a core working group. Results: A total of 145
      distinct entries were made in the original mind mapping procedure. The subsequent
      steps allowed us to reduce and condense the taxonomy into a final product
      consisting of 34 terms organized into three main categories: Food Choice, Eating
      Behavior, and Dietary Intake/Nutrition. In a live discussion session attended by
      50 of the scholars involved in the development of the taxonomy, it was judged to
      adequately reflect their input and to be a valid and useful starting point for
      interdisciplinary understanding and collaboration. Conclusion: The current
      taxonomy can be used as a tool to facilitate understanding and cooperation
      between different disciplines investigating dietary behavior, which may
      contribute to a more successful approach to tackling the complex public health
      challenges faced by the field. The taxonomy need not be viewed as a final
      product, but can continue to grow in depth and width as additional experts
      provide their input.

PMID- 30298029
TI  - Comparison of the Personality Traits of Male and Female BASE Jumpers.
AB  - BASE jumping is an extreme adventure sport which consists of jumping from a fixed
      object with specially adapted parachutes. A few studies of the personality of
      BASE jumpers have been conducted, but little is known about how the women in this
      sport compare to the men. The purpose of this study is to compare the personality
      traits among a sample of men and women who are experienced BASE jumpers, as this
      provides an interesting and important opportunity to better understand the
      motivation for extreme sports. Eighty-three participants completed the
      Temperament and Character Inventory the day before the jump at the New River
      Gorge Bridge Day BASE Jumping event, West Virginia, United States. The sample
      included 64 men and 19 women. Results show that men and women BASE jumpers shared
      similar personality traits both in terms of temperament and character, except for
      the character trait of cooperativeness on which women scored higher than men.
      This suggests that the basic drive for participation in extreme sports is self
      regulation of personal emotional drives and needs for self-actualization, rather
      than to oppose social pressure or cultural bias against female participation.
      These findings are discussed in relation with other studies conducted among
      extreme athletes and in terms of congruence between personality and activity.

PMID- 30298031
TI  - The Effect of Pairing Individuals With Different Social Skills on Interpersonal
      Motor Coordination.
AB  - Previous studies have demonstrated that combining individuals with different
      social skills affects performance in rhythmic interpersonal motor coordination,
      with individuals with lower social skills, such as individuals with autism
      spectrum disorder or schizophrenia, being found to follow the actions of partners
      with higher social skills. In this study, we investigated whether this finding
      could be generalized among pairs of individuals without disability. To perform
      this, we applied an interpersonal motor coordination task that required
      participants to perform rhythmic movements featuring an interpersonal relative
      phase pattern of 90 degrees . We did not assign the two roles (i.e., the
      preceding and following roles) to the participants, meaning they were forced to
      determine which roles to adopt by observing each other's movements, without
      verbal communication. Individual social skills were measured using the autism
      spectrum quotient (AQ). We found that pairs of participants with widely differing
      AQ scores performed better than did pairs with similar AQ scores. Most notably,
      the participants with higher AQ scores tended to precede their partners in the
      present task, which is the opposite result to that reported in previous studies.
      Our findings suggest that paring individuals without disability according to
      their social skills influences their interpersonal coordination performance in
      tasks wherein they must determine the preceding and following roles themselves.

PMID- 30298028
TI  - Gray Matter Structural Alterations in Social Anxiety Disorder: A Voxel-Based Meta
      Analysis.
AB  - The current insight into the neurobiological pathogenesis underlying social
      anxiety disorder (SAD) is still rather limited. We implemented a meta-analysis to
      explore the neuroanatomical basis of SAD. We undertook a systematic search of
      studies comparing gray matter volume (GMV) differences between SAD patients and
      healthy controls (HC) using a whole-brain voxel-based morphometry (VBM) approach.
      The anisotropic effect size version of seed-based d mapping (AES-SDM) meta
      analysis was conducted to explore the GMV differences of SAD patients compared
      with HC. We included eleven studies with 470 SAD patients and 522 HC in the
      current meta-analysis. In the main meta-analysis, relative to HC, SAD patients
      showed larger GMVs in the left precuneus, right middle occipital gyrus (MOG) and
      supplementary motor area (SMA), as well as smaller GMV in the left putamen. In
      the subgroup analyses, compared with controls, adult patients (age >= 18 years)
      with SAD exhibited larger GMVs in the left precuneus, right superior frontal
      gyrus (SFG), angular gyrus, middle temporal gyrus (MTG), MOG and SMA, as well as
      a smaller GMV in the left thalamus; SAD patients without comorbid depressive
      disorder exhibited larger GMVs in the left superior parietal gyrus and precuneus,
      right inferior temporal gyrus, fusiform gyrus, MTG and superior temporal gyrus
      (STG), as well as a smaller GMV in the bilateral thalami; and currently drug-free
      patients with SAD exhibited a smaller GMV in the left thalamus compared with HC
      while no larger GMVs were found. For SAD patients with different clinical
      features, our study revealed directionally consistent larger cortical GMVs and
      smaller subcortical GMVs, including locationally consistent larger precuneus and
      thalamic deficits in the left brain. Age, comorbid depressive disorder and
      concomitant medication use of the patients might be potential confounders of SAD
      at the neuroanatomical level.

PMID- 30298032
TI  - Counseling and Psychology Student Experiences of Personal Therapy: A Critical
      Interpretive Synthesis.
AB  - Background: Committing to attendance at personal therapy sessions is frequently
      either mandated or encouraged in many different types of therapeutic trainings
      across allied health, psychotherapy, social work and counseling. The small number
      of published accounts have indicated that student experiences of personal therapy
      can be mixed. Methods: The project examined contemporary interview based research
      about student experience of personal therapy during training using Critical
      Interpretive Synthesis method. Ten papers were found which met the search
      criteria. The papers included a total of 89 participants (75 F). Results: The
      results comprised 12 themes derived from 89 meaning units gleaned from student
      experiences presented in the research studies. These were used to inform a
      synthesizing statement here truncated as follows: Beginning therapy is
      challenging for some students, especially when attendance is mandatory. However,
      students can experience transformative change by the end of the process, even if
      they commence the work in a guarded way. Multiple problems can arise in the
      process of attending therapy as a student, and it can be difficult for a student
      to know what to do if these challenges are overwhelming. Attending personal
      therapy brings rich learnings which can be applied in clinical work but can also
      positively impact learning in the course, and lifelong personal development. The
      process can enhance the student's understanding of what the client may experience
      in the therapeutic journey. Conclusions: Attending personal therapy during
      training is not a straightforward process for all students. Course leaders and
      trainers need to be mindful of the possibility that students will struggle with
      the personal therapy requirement. Course and professional bodies should regularly
      review personal therapy requirements, being clear about the aims; remaining
      attuned to the student experience.

PMID- 30298033
TI  - Self-Regulation Shift Theory: A Dynamic Personal Agency Approach to Recovery
      Capital and Methodological Suggestions.
AB  - Recovery capital highlights person and environmental resources associated with
      overcoming significant life challenges. This paper utilizes social cognitive
      theory as a framework for understanding how recovery capital functions in trauma
      adaptation. This theory outlines the bidirectional, dynamic interactions among
      person (e.g., cognitive and affective), behavioral (e.g., problem focused
      coping), and environmental variables (i.e., triadic reciprocal determinism). The
      value of this approach to understanding human adaptation to trauma is that it
      targets the self-regulatory processes that unfold for trauma survivors as they
      attempt to put their lives back together. Self-regulation shift theory (SRST), as
      an extension to social cognitive theory, is offered to explain how self
      regulation is involved in both positive and negative adjustment. The theory uses
      a dynamical systems approach and highlights the mechanisms related to non-linear
      shifts in both positive and negative trauma recovery. According to SRST, trauma
      recovery may not be linear with threshold shifts (i.e., bifurcations) from one
      organized state (broken self) to another (empowered self). Coping self-efficacy
      perceptions are a critical factor influencing these threshold shifts. This paper
      concludes with a brief review of study designs and analytic procedures that can
      facilitate the application of non-linear dynamic research in this area.

PMID- 30298034
TI  - Investigating Humor in Social Interaction in People With Intellectual
      Disabilities: A Systematic Review of the Literature.
AB  - Background: Humor, both producing and appreciating, underpins positive social
      interactions. It acts as a facilitator of communication. There are clear links to
      wellbeing that go along with this form of social engagement. However, humor
      appears to be a seldom studied, cross-disciplinary area of investigation when
      applied to people with an intellectual disability. This review collates the
      current state of knowledge regarding the role of humor behavior in the social
      interactions of people with intellectual disabilities and their carers. Method: A
      systematic review utilizing the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses (PRISMA) guidelines was completed, which aimed to explore the
      current state of knowledge and quality of empirical evidence relating to humor in
      people with intellectual disabilities. Following this, articles were grouped
      thematically and summarized. A comprehensive search of four electronic databases
      (1954-2017) and additional search strategies yielded 32 articles which met the
      final inclusion criteria. Results: Humor played a significant positive and
      negative role in the social interactions of people with intellectual
      disabilities. Research had investigated humor in the classroom and humor
      expression in different groups including those with autism, Down syndrome,
      Angelman syndrome, Williams syndrome, and Rett syndrome. Few investigations
      directly studied humor appreciation and comprehension. Humor comprehension was
      reportedly supported by gestures. Some groups with intellectual disabilities
      found non-literal humor (e.g., sarcasm, irony) more difficult to understand,
      which may affect social relationships. Various types of humor were found to be
      appreciated. The role of humor in relationship development, social facilitation,
      creativity, and stigma had all received some limited attention. Humor also played
      a role for carer groups in coping with and enjoying the caring role. Research
      varied in quality with few experimental studies and mainly quasi-experimental and
      well-conducted, qualitative studies. Conclusions: This review revealed the
      importance of humor behavior in many aspects of the social lives of people with
      intellectual disabilities. Limited disparate research exists pertaining to humor
      in this group, suggesting the need for further robust research in this area,
      including more high quality primary research in the areas of humor production,
      appreciation, comprehension, and stigma.

PMID- 30298035
TI  - Effectiveness of a Positive Parental Practices Training Program for Chilean
      Preschoolers' Families: A Randomized Controlled Trial.
AB  - Background: Evidence for the effectiveness of parental training as a strategy for
      promotion of positive parental practices and prevention of child behavior
      problems in low and middle income countries is not conclusive. This study aims to
      assess the effectiveness of a universal positive parental training program
      designed for this context, "Dia a Dia" UdeC (c) ("Day by Day" University of
      Concepcion), in Chilean preschoolers' families (3-6 years old children). Methods:
      A cluster randomized controlled trial (cRCT) was carried out in 19 preschool
      education centers. There were two treatment arms: 10 centers (including 178
      families) were randomly assigned to the intervention group and nine centers
      (including 154 families) were assigned to the waiting list control condition.
      Intervention groups received Day by Day UdeC, a six group sessions program for
      parents, including two group sessions for preschool educators, focused in
      affective communication; daily and child-directed play; directed attention;
      routines and transitions; reinforcement and incentive programs; planned
      inattention-ignore and time out; and logical consequences. Parental practices,
      parental satisfaction, and presence of children behavioral problems were examined
      at two-time points: T1 (4 weeks before intervention) and T2 (5-6 weeks after
      intervention). Results: Intention-to-treat analysis shows a reduction in physical
      punishment and an increase in parental involvement, as well as a reduction in
      children behavioral problems. A per-protocol analysis revealed an additional
      effect: increase in observed parental practices. Conclusion: This cRCT provided
      evidence for the effectiveness of a parental training program for the promotion
      of positive parental practices in low and middle income countries. The observed
      effects of the program in decreasing physical punishment and children's
      behavioral problems make it a promising strategy for prevention purposes. Trial
      Registration: This study was registered under ISRCTN.com (ISRCTN90762146;
      https://doi.org/10.1186/ISRCTN90762146).

PMID- 30298036
TI  - Neural Underpinnings of the Perception of Emotional States Derived From
      Biological Human Motion: A Review of Neuroimaging Research.
AB  - Research on the perception of biological human motion shows that people are able
      to infer emotional states by observing body movements. This article reviews the
      methodology applied in fMRI research on the neural representation of such emotion
      perception. Specifically, we ask how different stimulus qualities of bodily
      expressions, individual emotional valence, and task instructions may affect the
      neural representation of an emotional scene. The review demonstrates the
      involvement of a variety of brain areas, thereby indicating how well the human
      brain is adjusted to navigate in multiple social situations. All stimulus
      categories (i.e., full-light body displays, point-light displays, and avatars)
      can induce an emotional percept and are associated with increased activation in
      an extensive neural network. This network seems to be organized around areas
      belonging to the so-called action observation network (PMC, IFG, and IPL) and the
      mentalizing network (TPJ, TP, dmPFC, and lOFC) as well as areas processing body
      form and motion (e.g., EBA, FBA, and pSTS). Furthermore, emotion-processing brain
      sites such as the amygdala and the hypothalamus seem to play an important role
      during the observation of emotional body expressions. Whereas most brain regions
      clearly display an increased response to emotional body movements in general,
      some structures respond selectively to negative valence. Moreover, neural
      activation seems to depend on task characteristics, indicating that certain
      structures are activated even when attention is shifted away from emotional body
      movements.

PMID- 30298037
TI  - The Relationship Between Improvement in Insomnia Severity and Long-Term Outcomes
      in the Treatment of Chronic Fatigue.
AB  - Background: The current treatments of choice for patients with chronic fatigue
      are moderately effective. One way to advance treatments is identifying process
      variables associated with good treatment outcomes. There is little knowledge
      regarding a possible association between insomnia and long-term outcomes in the
      treatment of chronic fatigue. Aims: Testing whether (1) improvement in insomnia
      is associated with improvement in levels of fatigue at 1-year follow-up, and (2)
      if such a relationship remains when controlling for improvement in levels of
      anxiety and depression, and pain in patients with chronic fatigue. Methods:
      Patients having been on sick leave 8 weeks or more due to chronic fatigue were
      referred to a return-to-work program. They received an intensive 3.5-week
      inpatient treatment program based on acceptance and commitment therapy (ACT).
      Before treatment and at 1-year follow-up the patients completed questionnaires
      assessing levels of insomnia severity, pain, anxiety and depression, and fatigue.
      Results: A regression analysis found that changes in insomnia-severity were
      associated with changes in fatigue-levels at 1-year follow-up. When changes in
      levels of anxiety and depression were entered in the regression analysis, anxiety
      and depression was significantly associated with levels of fatigue but insomnia
      was not. The association between anxiety and depression and fatigue was at a
      trend level when pain was entered into the model. Conclusion: Long-term
      improvement in insomnia severity was significantly associated with long-term
      improvement in chronic fatigue, but not independently of long-term improvement in
      anxiety and depression, and pain. Trial Registration:
      https://clinicaltrials.gov/, identifier NCT01568970.

PMID- 30298039
TI  - Happily Unhelpful: Infants' Everyday Helping and its Connections to Early
      Prosocial Development.
AB  - Young children's everyday helping in the home has received relatively little
      attention in research on prosocial behavior. Nevertheless, key features such as
      young children's cheerful participation in chores around the home, including in
      ways that make accomplishing these chores more difficult for parents, can reveal
      important facets of early prosocial development. The present study reports the
      results of an Internet (MTurk) survey of over 500 families with children aged 1-4
      years about their children's prosocial tendencies, participation in nine common
      chores, whether children's helping attempts were helpful or not, and attributions
      about children's motives for helping. Consistent with much prior research,
      parents reported that children became more prosocial with age. The majority of
      parents reported children's participation in everyday helping is at times
      unhelpful. Parents attributed children's helping to a variety of motives and
      these too, changed with age. Fathers had somewhat different perceptions of
      children's everyday helping than mothers. Results are discussed in terms of how
      understanding everyday helping can contribute to ongoing debates in the
      literature about the roots of prosocial behavior.

PMID- 30298038
TI  - High Schizotypal Individuals Are More Creative? The Mediation Roles of
      Overinclusive Thinking and Cognitive Inhibition.
AB  - Although a theoretical link between positive schizotypy and heightened creativity
      has been established in the literature, little empirical research has been
      conducted to examine the underlying cognitive processes that contribute to this
      association. In addition, previous studies found a negative relationship between
      positive schizotypy and cognitive inhibition; however, they often used the
      paradigm of latent inhibition. This study used the paradigm of prepotent response
      inhibition indicated by Stroop interference effect and examined the mediation
      effects of overinclusive thinking (OT) and cognitive inhibition on the creativity
      of schizotypal individuals. Two groups of low and high schizotypal individuals (N
      = 78) participated in the study. Each participant completed one OT task, one
      color-word Stroop task, three other executive functioning (EF) control tasks, and
      two creativity tasks. The results indicated that the high schizotypal group
      outperformed the low schizotypal group in the creativity tasks. They also
      exhibited higher OT as indicated by faster reaction time and higher cognitive
      inhibition as indicated by lower Stroop interference effect. Further,
      participant's levels of OT and cognitive inhibition partially mediated the
      relationship between schizotypy and creativity. The results were discussed under
      the context of schizotypy and creativity research and implications for
      rehabitation were further provided.

PMID- 30298040
TI  - Engaging in Creativity Broadens Attentional Scope.
AB  - Previous studies have shown that creativity is enhanced by a broad attentional
      scope, defined as an ability to utilize peripheral stimuli and process
      information globally. We propose that the reverse relationship also holds, and
      that breadth of attention also is a consequence of engaging in a creative
      activity. In Study 1, participants showed increased breadth of attention in a
      visual scanning task after performing a divergent thinking task as opposed to an
      analytic thinking task. In Study 2, participants recognized peripheral stimuli
      displayed during the task better after performing a divergent thinking task as
      compared to an analytic task, whereas recognition performance of participants
      performing a task that involves a mix of divergent and analytic thinking (the
      Remote Associates Test) fell in between. Additionally, in Study 2 (but not in
      Study 1), breadth of attention was positively correlated with performance in a
      divergent thinking task, but not with performance in an analytic thinking task.
      Our findings suggest that the adjustment of the cognitive system to task demands
      manifests at a very basic, perceptual level, through changes in the breadth of
      visual attention. This paper contributes a new, motivational perspective on
      attentional breadth and discusses it as a result of adjusting cognitive
      processing to the task requirements, which contributes to effective self
      regulation.

PMID- 30298041
TI  - The Buffering Effect of Machiavellianism on the Relationship Between Role
      Conflict and Counterproductive Work Behavior.
AB  - Considering the destructive effects of counterproductive work behavior (CWB) in
      the workplace, scholars have put much effort into revealing its antecedents. The
      purpose of this paper is to examine how Machiavellianism helps mitigate the
      effect of role conflict on CWB in China. Using data collected from three phases,
      this research revealed that role conflict had a positive effect on CWB via
      emotional exhaustion. Machiavellianism moderated the relationship between role
      conflict and emotional exhaustion, such that this relationship got weaker for
      employees with higher Machiavellianism. Furthermore, Machiavellianism moderated
      the relationship between role conflict and CWB via emotional exhaustion, as such,
      it became weaker for employees with high Machiavellianism.

PMID- 30298042
TI  - Let's Read a Poem! What Type of Poetry Boosts Creativity?
AB  - Poetry is one of the most creative uses of language. Yet the influence of poetry
      on creativity has received little attention. The present research aimed to
      determine how the reception of different types of poetry affect creativity
      levels. In two experimental studies, participants were assigned to two
      conditions: poetry reading and non-poetic text reading. Participants read poems
      (Study 1 = narrative/open metaphors; Study 2 = descriptive/conventional
      metaphors) or control pieces of non-poetic text. Before and after the reading
      manipulation, participants were given a test to determine levels of divergent
      thinking (DT; i.e., fluency, flexibility, and originality). Additionally, in both
      studies, the impact of frequent contact with poetry was examined. In Study 1 (N =
      107), participants showed increased fluency and flexibility after reading a
      narrative poem, while participants who read the non-poetic text showed a decrease
      in fluency and originality. In Study 2 (N = 131) reception of conventional,
      closed metaphorization significantly lowered fluency and flexibility of thinking
      (compared to reading non-poetic text). The most critical finding was that poetry
      exposure could either increase or decrease creativity level depending on the type
      of poetic metaphors and style of poetic narration. Furthermore, results indicate
      that long-term exposure to poetry is associated with creativity. This interest in
      poetry can be explained by an ability to immerse oneself in a poetry content
      (i.e., a type of empathy) and the need for cognitive stimulation. Thus, this
      paper contributes a new perspective on exposure to poetry in the context of
      creativity and discusses possible individual differences that may affect how this
      type of art is received. However, future research is necessary to examine these
      associations further.

PMID- 30298043
TI  - Jamaican Mothers' Perceptions of Children's Strategies for Resisting Parental
      Rules and Requests.
AB  - Research on Jamaican socialization of children has primarily focused on parental
      discipline practices. Little is known about children's responses to parental
      attempts to control their behavior. The present study investigated mothers'
      perceptions of children's strategies for resisting their rules and requests.
      Thirty mothers living in Kingston and St. Andrew, Jamaica, participated in a 1-
      to 1.5-h semi-structured, open-ended interview regarding their 8- to 12-year-old
      children. Mothers reported that their children's resistance strategies included
      assertive refusal, arguing, ignoring/avoiding, attitude, and negotiation. Most
      mothers disapproved of their children's actions and responded with power
      assertive strategies such as physical punishment, psychological control, forced
      compliance, and threats. Few mothers responded with autonomy support strategies
      including accommodation and reasoning. The findings provided insight into the
      ways Jamaican children use their agency to protect their autonomy despite their
      mothers' greater power, and the relational nature of children's influence on
      their mothers' behaviors and reactions. More research is needed to expand our
      knowledge of child agency in Afro-Caribbean families and the various ways that
      parents may support their growing autonomy that is socially constructive.

PMID- 30298044
TI  - Theory of Mind Development in School-Aged Left-Behind Children in Rural China.
AB  - The current study aimed to investigate differences in theory of mind between left
      behind children and non-left-behind children in rural China and to examine the
      potential protective role of general reasoning ability in left-behind children's
      theory of mind. Participants included 213 children aged 7.10-13.67 years (111
      boys and 102 girls, M = 10.51 years, SD = 1.33), 101 of whom were left behind in
      rural areas by one or both migrating parents for at least 6 months. The Strange
      Stories task, a second-order false belief task, and a faux pas task were used to
      measure children's theory of mind, and Sessions B and C in Raven's Standard
      Progressive Matrices were used to test children's general reasoning ability. The
      results showed that left-behind children scored lower on both the faux pas task
      and Strange Stories task. Additionally, on second-order false belief
      understanding, left-behind boys performed worse than non-left-behind boys, while
      left-behind girls scored higher than non-left behind girls. Moreover, children's
      general reasoning ability moderated the relationship between parental migrant
      status and children's faux pas understanding: For children with high levels of
      general reasoning ability, left-behind children performed similarly to non-left
      behind children, while for children with low levels of general reasoning ability,
      left-behind children scored lower than non-left-behind children, indicating that
      general reasoning ability buffered the negative effect of being left behind on
      children's theory of mind development. The implications of these findings for
      training directed at left-behind children are discussed.

PMID- 30298046
TI  - Palinopsia Following Acute Unilateral Partial Vestibular Deafferentation: A Case
      Report.
AB  - Palinopsia is defined as the persistence or reappearance of images after
      cessation of the visual stimulus. One patient presented episodes of palinopsia
      after the functional loss of the 3 semicircular canals of the right ear while the
      otolithic function was preserved. None of classical causes was identified in this
      patient, intoxications, brain tumors, migraines, psychiatric disorders, etc. For
      a movement to be perceived as a single event, central processes of temporal
      integration are necessary to correct the shift between the rapid vestibular
      information, and the slow visual information. However, it has been shown on
      animal models that vestibular inputs are slower than normal in case of peripheral
      deafferentation limited to the canalar function with preservation of the
      otolithic function, which is the case in this patient. Therefore, we hypothesize
      that episodes of palinopsia he presents result from the fact that temporal
      integration processes do not take into account the slower than normal vestibular
      information due to the peripheral disorder and continue to slow it down. Thus,
      the patient keeps the visual image in memory until the late arrival of the
      vestibular information.

PMID- 30298045
TI  - Neuropsychological and Psychological Functioning Aspects in Myotonic Dystrophy
      Type 1 Patients in Italy.
AB  - Introduction: Myotonic Dystrophy Type 1 (DM1) is an autosomal dominant genetic
      illness, characterized by a progressive loss of strength. Important deficits in
      cognitive functioning and a significant prevalence of psychiatric disorders have
      been previously reported. Methods:A neuropsychological and psychological
      assessment was carried out in 31 DM1 patients (61% males) in order to measure the
      cognitive functioning and explore their personality profiles. The MMSE Mini
      Mental State Examination, Frontal Assessment Battery (FAB), ENB-2 Battery
      assessing memory (short term, long term and working memory), integration
      capacities, visual-spatial ability, attention (selective, divided,
      shifting/switching) executive functions, praxis, discrimination and logic
      capabilities and psychopathology Symptom Check List 90-R (SCL-90-R) were
      administered. The neuropsychological and psychological evaluation of DM1 patients
      was carried out taking into consideration the clinical parameters (CTG repeat,
      age at onset, disease duration, Muscular Impairment Rate Scale (MIRS), Medical
      Research Council Scale (MRC) and the Epworth Sleepiness Scales (EPS)). Results:
      Regarding psychopathology 19.4% of patients scored a moderate or high level of
      symptoms intensity index (GSI), 12.9% reported a high number of symptoms (PST)
      and 16.1% reported a high intensity level of the perceived symptoms (PSDI).
      Fatigue and daytime sleepiness resulted as being associated with higher levels of
      psychoticism (PSY). Only 1 patient reported a severe impairment in the spatial
      and temporal orientation, memory, language, praxis, attention and calculation.
      Longer disease duration was also associated with cognitive impairment evaluated
      through ENB-2 (p < 0.05). Discussions and Conclusions:There are indications of
      the utility of neuropsychological and psychological screening and support for
      these patients and their families due to the link between disease duration and
      cognitive performances. A proposal of a clinical protocol, with an illustration
      of a clinical case report of a family is presented.

PMID- 30298047
TI  - Differentiation of Brain Metastases and Gliomas Based on Color Map of Phase
      Difference Enhanced Imaging.
AB  - Background and objective: Phase difference enhanced imaging (PADRE), a new phase
      related MRI technique, can enhance both paramagnetic and diamagnetic substances,
      and select which phases to be enhanced. Utilizing these characteristics, we
      developed color map of PADRE (Color PADRE), which enables simultaneous
      visualization of myelin-rich structures and veins. Our aim was to determine
      whether Color PADRE is sufficient to delineate the characteristics of non
      gadolinium-enhancing T2-hyperintense regions related with metastatic tumors
      (MTs), diffuse astrocytomas (DAs) and glioblastomas (GBs), and whether it can
      contribute to the differentiation of MTs from GBs. Methods: Color PADRE images of
      11 patients with MTs, nine with DAs and 17 with GBs were created by combining
      tissue-enhanced, vessel-enhanced and magnitude images of PADRE, and then
      retrospectively reviewed. First, predominant visibility of superficial white
      matter and deep medullary veins within non-gadolinium-enhancing T2-hyperintense
      regions were compared among the three groups. Then, the discriminatory power to
      differentiate MTs from GBs was assessed using receiver operating characteristic
      analysis. Results: The degree of visibility of superficial white matter was
      significantly better in MTs than in GBs (p = 0.017), better in GBs than in DAs (p
      = 0.014), and better in MTs than in DAs (p = 0.0021). On the contrary, the
      difference in the visibility of deep medullary veins was not significant (p =
      0.065). The area under the receiver operating characteristic curve to
      discriminate MTs from GBs was 0.76 with a sensitivity of 80% and specificity of
      64%. Conclusion: Visibility of superficial white matter on Color PADRE reflects
      inferred differences in the proportion of vasogenic edema and tumoral
      infiltration within non-gadolinium-enhancing T2-hyperintense regions of MTs, DAs
      and GBs. Evaluation of peritumoral areas on Color PADRE can help to distinguish
      MTs from GBs.

PMID- 30298048
TI  - New Insights on Emotional Contributions to Human Postural Control.
AB  - It has been just over 20 years since the effects of height-induced threat on
      human postural control were first investigated. Raising the height of the support
      surface on which individuals stood increased the perceived consequences of
      instability and generated postural control changes. Since this initial work,
      converging evidence has accumulated supporting the efficacy of using height
      induced threat to study the effects of emotions on postural control and
      confirming a direct influence of threat-related changes in arousal, anxiety, and
      fear of falling on all aspects of postural control, including standing,
      anticipatory, and reactive balance. In general, threat-related postural changes
      promote a greater physical safety margin while maintaining upright stance. We use
      the static balance literature to critically examine the current state of
      knowledge regarding: (1) the extent to which threat-related changes in postural
      control are sensitive to threat-related changes in emotions; (2) the underlying
      neurophysiological and cognitive mechanisms that may contribute to explaining the
      relationship between emotions and postural control; and (3) the generalizability
      of threat-related changes across different populations and types of threat. These
      findings have important implications for understanding the neuromechanisms that
      control healthy balance, and highlight the need to recognize the potential
      contributions of psychological and physiological factors to balance deficits
      associated with age or pathology. We conclude with a discussion of the practical
      significance of this research, its impact on improving diagnosis and treatment of
      postural control deficits, and potential directions for future research.

PMID- 30298049
TI  - HIV-1-Associated Neurocognitive Disorders: Is HLA-C Binding Stability to beta2
      Microglobulin a Missing Piece of the Pathogenetic Puzzle?
AB  - AIDS dementia complex (ADC) and HIV-associated neurocognitive disorders (HAND)
      are complications of HIV-1 infection. Viral infections are risk factors for the
      development of neurodegenerative disorders. Aging is associated with low-grade
      inflammation in the brain, i.e., the inflammaging. The molecular mechanisms
      linking immunosenescence, inflammaging and the pathogenesis of neurodegenerative
      disorders, such as Alzheimer's disease (AD) and Parkinson's disease, are largely
      unknown. ADC and HAND share some pathological features with AD and may offer some
      hints on the relationship between viral infections, neuroinflammation, and
      neurodegeneration. beta2-microglobulin (beta2m) is an important pro-aging factor
      that interferes with neurogenesis and worsens cognitive functions. Several
      studies published in the 80-90s reported high levels of beta2m in the
      cerebrospinal fluid of patients with ADC. High levels of beta2m have also been
      detected in AD. Inflammatory diseases in elderly people are associated with
      polymorphisms of the MHC-I locus encoding HLA molecules that, by associating with
      beta2m, contribute to cellular immunity. We recently reported that HLA-C, no
      longer associated with beta2m, is incorporated into HIV-1 virions, determining an
      increase in viral infectivity. We also documented the presence of HLA-C variants
      more or less stably linked to beta2m. These observations led us to hypothesize
      that some variants of HLA-C, in the presence of viral infections, could determine
      a greater release and accumulation of beta2m, which in turn, may be involved in
      triggering and/or sustaining neuroinflammation. ADC is the most severe form of
      HAND. To explore the role of HLA-C in ADC pathogenesis, we analyzed the frequency
      of HLA-C variants with unstable binding to beta2m in a group of patients with
      ADC. We found a higher frequency of unstable HLA-C alleles in ADC patients, and
      none of them was harboring stable HLA-C alleles in homozygosis. Our data suggest
      that the role of HLA-C variants in ADC/HAND pathogenesis deserves further
      studies. If confirmed in a larger number of samples, this finding may have
      practical implication for a personalized medicine approach and for developing new
      therapies to prevent HAND. The exploration of HLA-C variants as risk factors for
      AD and other neurodegenerative disorders may be a promising field of study.

PMID- 30298050
TI  - 3-Iodothyronamine Activates a Set of Membrane Proteins in Murine Hypothalamic
      Cell Lines.
AB  - 3-Iodothyronamine (3-T1AM) is an endogenous thyroid hormone metabolite. The
      profound pharmacological effects of 3-T1AM on energy metabolism and thermal
      homeostasis have raised interest to elucidate its signaling properties in tissues
      that pertain to metabolic regulation and thermogenesis. Previous studies
      identified G protein-coupled receptors (GPCRs) and transient receptor potential
      channels (TRPs) as targets of 3-T1AM in different cell types. These two
      superfamilies of membrane proteins are largely expressed in tissue which
      influences energy balance and metabolism. As the first indication that 3-T1AM
      virtually modulates the function of the neurons in hypothalamus, we observed that
      intraperitoneal administration of 50 mg/kg bodyweight of 3-T1AM significantly
      increased the c-FOS activation in the paraventricular nucleus (PVN) of C57BL/6
      mice. To elucidate the underlying mechanism behind this 3-T1AM-induced
      signalosome, we used three different murine hypothalamic cell lines, which are
      all known to express PVN markers, GT1-7, mHypoE-N39 (N39) and mHypoE-N41 (N41).
      Various aminergic GPCRs, which are the known targets of 3-T1AM, as well as
      numerous members of TRP channel superfamily, are expressed in these cell lines.
      Effects of 3-T1AM on activation of GPCRs were tested for the two major signaling
      pathways, the action of Galphas/adenylyl cyclase and Gi/o. Here, we demonstrated
      that this thyroid hormone metabolite has no significant effect on Gi/o signaling
      and only a minor effect on the Galphas/adenylyl cyclase pathway, despite the
      expression of known GPCR targets of 3-T1AM. Next, to test for other potential
      mechanisms involved in 3-T1AM-induced c-FOS activation in PVN, we evaluated the
      effect of 3-T1AM on the intracellular Ca2+ concentration and whole-cell currents.
      The fluorescence-optic measurements showed a significant increase of
      intracellular Ca2+ concentration in the three cell lines in the presence of 10
      MUM 3-T1AM. Furthermore, this thyroid hormone metabolite led to an increase of
      whole-cell currents in N41 cells. Interestingly, the TRPM8 selective inhibitor
      (10 MUM AMTB) reduced the 3-T1AM stimulatory effects on cytosolic Ca2+ and whole
      cell currents. Our results suggest that the profound pharmacological effects of 3
      T1AM on selected brain nuclei of murine hypothalamus, which are known to be
      involved in energy metabolism and thermoregulation, might be partially
      attributable to TRP channel activation in hypothalamic cells.

PMID- 30298051
TI  - Exosomes Derived From Mesenchymal Stromal Cells Pretreated With Advanced
      Glycation End Product-Bovine Serum Albumin Inhibit Calcification of Vascular
      Smooth Muscle Cells.
AB  - Background: The osteogenic differentiation of vascular smooth muscle cell (VSMCs)
      is important for the development of vascular calcification (VC), particularly in
      diabetes. Exosomes derived from Mesenchymal Stromal Cells (MSCs) are effective
      against cardiovascular diseases, yet their role in VC remains unclear. Advanced
      glycation end products (AGEs) inhibit bone marrow stromal cell osteogenesis by
      targeting osteogenesis-associated genes. Thus, we investigated the role of
      exosomes derived from MSCs pretreated with AGEs-BSA in VC and its potential
      mechanisms. Methods: Primary VSMCs and MSCs were isolated from the aorta and bone
      marrow of Sprague-Dawley rats, respectively. VSMCs were cultured with AGEs-BSA to
      induce osteogenic differentiation. Exosomes were harvested from MSCs by
      ultracentrifugation. MSCs and VSMCs were cocultured in Transwells, and exosomes
      were added to VSMC culture medium to assess their effects on osteogenic
      differentiation. Double luciferase reporter assay was applied to confirm that miR
      146a directly targets the 3' UTR of the thioredoxin-interacting protein (TXNIP)
      gene. Results: Pretreatment of VSMCs with AGEs-BSA increased the expression of
      thioredoxin-interacting protein (TXNIP) by inhibiting that of miR-146a, resulting
      in enhanced ROS production and VSMC calcification. By contrast, the expression of
      miR-146a in MSCs was increased by AGEs-BSA treatment. Thus, miR-146a was
      transferred from AGEs-BSA-pretreated or miR-146a-transfected MSCs to VSMCs via
      exosomes. After coculture with miR-146a-containing exosomes, the AGEs-BSA
      mediated increase in VSMC calcification was diminished, accompanied by decreased
      TXNIP expression and ROS production. Furthermore, TXNIP overexpression
      counteracted the anti-calcification effects of MSC-derived miR-146a-containing
      exosomes. In addition, TXNIP was identified as a target gene of miR-146a, and the
      results of double luciferase reporter assay confirmed that TXNIP was the direct
      target gene of miR-146a. Conclusions: Exosomes secreted by MSCs pretreated with
      AGEs-BSA contained a high level of miR-146a, which was transferred to VSMCs and
      inhibited AGEs-BSA-induced calcification in a TXNIP-dependent manner. Thus, miR
      146a-containing exosomes may be a potential therapeutic target for VC.

PMID- 30298052
TI  - The Antidiabetic Drug Lobeglitazone Protects Mice From Lipogenesis-Induced Liver
      Injury via Mechanistic Target of Rapamycin Complex 1 Inhibition.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder closely linked
      with type II diabetes (T2D). The progression of NAFLD is associated with the
      induction of lipogenesis through hyperactivation of the mechanistic target of
      rapamycin complex 1 (mTORC1) pathway. An increase in lipogenesis induces
      endoplasmic reticulum (ER) stress and accelerates oxidative liver injury in the
      pathogenesis of NAFLD. Lobeglitazone, one of thiazolidinediones (TZDs), is used
      as an antidiabetic drug to lower serum glucose level through an increase in
      insulin sensitivity. It is known to improve pathological symptoms in animals and
      humans with NAFLD. However, the underlying molecular mechanism of the protective
      effects of lobeglitazone against NAFLD has not been elucidated. Here, we show
      that under the physiological condition of acute lipogenesis, lobeglitazone
      inhibits hepatic lipid synthesis, the subsequent ER stress, and omega-oxidation
      of fatty acids by inhibiting the mTORC1 pathway. As a result, lobeglitazone
      protected mice from lipogenesis-induced oxidative liver injury. Taken together,
      lobeglitazone might be a suitable drug for the treatment of patients with
      diabetes and NAFLD.

PMID- 30298053
TI  - Excessive Neutrophil Activity in Gestational Diabetes Mellitus: Could It
      Contribute to the Development of Preeclampsia?
AB  - Gestational diabetes mellitus is a transient form of glucose intolerance
      occurring during pregnancy. Pregnancies affected by gestational diabetes mellitus
      are at risk for the development of preeclampsia, a severe life threatening
      condition, associated with significant feto-maternal morbidity and mortality. It
      is a risk factor for long-term health in women and their offspring. Pregnancy has
      been shown to be associated with a subliminal degree of neutrophil activation and
      tightly regulated generation of neutrophil extracellular traps (NETs). This
      response is excessive in cases with preeclampsia, leading to the presence of
      large numbers of NETs in affected placentae. We have recently observed that
      circulatory neutrophils in cases with gestational diabetes mellitus similarly
      exhibit an excessive pro-NETotic phenotype, and pronounced placental presence, as
      detected by expression of neutrophil elastase. Furthermore, exogenous neutrophil
      elastase liberated by degranulating neutrophils was demonstrated to alter
      trophoblast physiology and glucose metabolism by interfering with key signal
      transduction components. In this review we examine whether additional evidence
      exists suggesting that altered neutrophil activity in gestational diabetes
      mellitus may contribute to the development of preeclampsia.

PMID- 30298056
TI  - In silico Prediction and Exploration of Potential Bacteriocin Gene Clusters
      Within the Bacterial Genus Geobacillus.
AB  - The thermophilic, endospore-forming genus of Geobacillus has historically been
      associated with spoilage of canned food. However, in recent years it has become
      the subject of much attention due its biotechnological potential in areas such as
      enzyme and biofuel applications. One aspect of this genus that has not been fully
      explored or realized is its use as a source of novel forms of the ribosomally
      synthesized antimicrobial peptides known as bacteriocins. To date only two
      bacteriocins have been fully characterized within this genus, i.e., Geobacillin I
      and II, with only a small number of others partially characterized. Here we
      bioinformatically investigate the potential of this genus as a source of novel
      bacteriocins through the use of the in silico screening software BAGEL3, which
      scans publically available genomes for potential bacteriocin gene clusters. In
      this study we examined the association of bacteriocin gene presence with niche
      and phylogenetic position within the genus. We also identified a number of
      candidates from multiple bacteriocin classes which may be promising antimicrobial
      candidates when investigated in vitro in future studies.

PMID- 30298054
TI  - Antibiotics, Resistome and Resistance Mechanisms: A Bacterial Perspective.
AB  - History of mankind is regarded as struggle against infectious diseases. Rather
      than observing the withering away of bacterial diseases, antibiotic resistance
      has emerged as a serious global health concern. Medium of antibiotic resistance
      in bacteria varies greatly and comprises of target protection, target
      substitution, antibiotic detoxification and block of intracellular antibiotic
      accumulation. Further aggravation to prevailing situation arose on observing
      bacteria gradually becoming resistant to different classes of antibiotics through
      acquisition of resistance genes from same and different genera of bacteria.
      Attributing bacteria with feature of better adaptability, dispersal of antibiotic
      resistance genes to minimize effects of antibiotics by various means including
      horizontal gene transfer (conjugation, transformation, and transduction), Mobile
      genetic elements (plasmids, transposons, insertion sequences, integrons, and
      integrative-conjugative elements) and bacterial toxin-antitoxin system led to
      speedy bloom of antibiotic resistance amongst bacteria. Proficiency of bacteria
      to obtain resistance genes generated an unpleasant situation; a grave, but a lot
      unacknowledged, feature of resistance gene transfer.

PMID- 30298055
TI  - The Lactobacillus casei Group: History and Health Related Applications.
AB  - The Lactobacillus casei group (LCG), composed of the closely related
      Lactobacillus casei, Lactobacillus paracasei, and Lactobacillus rhamnosus are
      some of the most widely researched and applied probiotic species of lactobacilli.
      The three species have been extensively studied, classified and reclassified due
      to their health promoting properties. Differentiation is often difficult by
      conventional phenotypic and genotypic methods and therefore new methods are being
      continually developed to distinguish the three closely related species. The group
      remain of interest as probiotics, and their use is widespread in industry. Much
      research has focused in recent years on their application for health promotion in
      treatment or prevention of a number of diseases and disorders. The LCG have the
      potential to be used prophylactically or therapeutically in diseases associated
      with a disturbance to the gut microbiota. The group have been extensively
      researched with regard to stress responses, which are crucial for their survival
      and therefore application as probiotics.

PMID- 30298057
TI  - Pathogenicity Induced by Invasive Infection of Streptococcus dysgalactiae subsp.
      equisimilis in a Mouse Model of Diabetes.
AB  - Streptococcus dysgalactiae subsp. equisimilis (SDSE) causes severe invasive
      diseases such as streptococcal toxic shock syndrome, similar to that caused by S.
      pyogenes (GAS). Invasive SDSE infections are increasing, particularly among
      patients with diabetes mellitus. Here we investigate the association between the
      pathogenicity of SDSE and diabetes mellitus in a mouse model, using GAS infection
      for comparison. Intraperitoneal injection of highly hemolytic SDSE-167 into
      C57BL6/J mice induced a rapid rise in blood glucose concentrations within 4 h,
      which was otherwise seen only in mice injected with high doses of hypervirulent
      GAS mutants. The survival rates of mice injected with SDSE-167 were significantly
      lower in mice (db/db) with type 2 diabetes than in nondiabetic mice. Injection of
      db/db mice with SDSE-167 increased the concentrations of cytokines and
      chemokines, particularly those of interleukin 6 and monocyte chemotactic protein
      1. Microarray data indicate that multiple pathways are involved in the
      pathogenicity of SDSE-167 in db/db mice. These data reveal that the mechanisms
      underlying streptococcal infection differ between SDSE and GAS.

PMID- 30298058
TI  - Isolation and Transcriptome Analysis of Phenol-Degrading Bacterium From Carbon
      Sand Filters in a Full-Scale Drinking Water Treatment Plant.
AB  - Phenol is a typical organic contaminant in the environment. To date, the
      biodegradation of phenol by microorganisms remains the preferred method for its
      removal and remediation, but data on phenol removal by drinking water biofilters
      are lacking. In this study, we used high-throughput sequencing to investigate the
      microbial community structure in a carbon-sand biofilter. The results indicated
      that the predominant bacterial group was Bacilli, followed by
      Gammaproteobacteria, Clostridia, and Alphaproteobacteria. In addition, a strain
      was capable of degrading phenol at low concentrations of 500 MUg/L within 100 min
      was isolated and identified as Rhodococcus sp. CS-1. Transcriptome analysis
      results showed that Rhodococcus sp. CS-1 was able to degrade phenol via both the
      catechol and protocatechuate branch of the beta-ketoadipate pathway. Furthermore,
      some novel candidate biomarkers (copper oxidase, copper chaperone, and
      MarR/DeoR/TetR family transcriptional regulators) were successfully identified to
      be potentially involved in phenol biodegradation. This study indicates that
      carbon-sand filters have the potential for remediation of phenol. The application
      of native microorganisms to drinking water treatment system is an adaptive
      strategy in oligotrophic water environments.

PMID- 30298059
TI  - Metabolic Engineering of Yeast for the Production of 3-Hydroxypropionic Acid.
AB  - The beta-hydroxy acid 3-hydroxypropionic acid (3-HP) is an attractive platform
      compound that can be used as a precursor for many commercially interesting
      compounds. In order to reduce the dependence on petroleum and follow sustainable
      development, 3-HP has been produced biologically from glucose or glycerol. It is
      reported that 3-HP synthesis pathways can be constructed in microbes such as
      Escherichia coli, Klebsiella pneumoniae and the yeast Saccharomyces cerevisiae.
      Among these host strains, yeast is prominent because of its strong acid tolerance
      which can simplify the fermentation process. Currently, the malonyl-CoA reductase
      pathway and the beta-alanine pathway have been successfully constructed in yeast.
      This review presents the current developments in 3-HP production using yeast as
      an industrial host. By combining genome-scale engineering tools, malonyl-CoA
      biosensors and optimization of downstream fermentation, the production of 3-HP in
      yeast has the potential to reach or even exceed the yield of chemical production
      in the future.

PMID- 30298060
TI  - Naturally Fermented Milk From Northern Senegal: Bacterial Community Composition
      and Probiotic Enrichment With Lactobacillus rhamnosus.
AB  - A variety of foods fermented with lactic acid bacteria serve as dietary staples
      in many African communities; yet, their bacterial profiles are poorly
      characterized. The integration of health-promoting probiotics into naturally
      fermented milk products could make a profound impact on human health. Here, we
      characterize the bacterial community composition of a naturally fermented milk
      product (lait caille) from northern Senegal, prepared in wooden bowls (lahals)
      with a bacterial biofilm to steer the fermentation process. We incorporated a
      probiotic starter culture containing the most documented probiotic strain
      Lactobacillus rhamnosus GG (generic strain name yoba 2012) into the local
      fermentation process. Bar-coded 16S rRNA amplicon sequencing of lait caille
      samples indicated that the bacterial community of lait caille has high species
      richness with over 100 bacterial genera; however, few have high abundance. In
      contrast to the diverse bacterial compositions of other characterized naturally
      fermented milk products, the composition of lait caille predominantly consists of
      the lactic acid bacteria Streptococcus and Lactobacillus, resembling the
      bacterial composition in regular yogurt. The bacterial community composition of
      lait caille varies geographically based on the presence of some genera, including
      Lactoccoccus, Enterococcus, Bifidobacterium, and Bacillus, but this trend is not
      consistent within production communities. The diversity of bacterial communities
      is much higher in the lahal biofilm than in the naturally fermented milk
      products, which is in turn greater than in commercial yogurts. Addition of a
      starter culture with L. rhamnosus yoba 2012 to milk in lahals led to substantial
      growth of this probiotic bacterium during the fermentation process. Two
      independent quantitative PCR-analyses specific for L. rhamnosus yoba 2012
      indicated a 20- to 60-fold increase in the total number of probiotic bacteria in
      the first batch after inoculation. A similar increase of the probiotic was
      observed in a variation of lait caille prepared with carbohydrate-rich millet
      granules (thiakry) added prior to fermentation. This study shows the feasibility
      of integrating health-promoting probiotic strains into naturally fermented foods
      produced in regions with a high prevalence of malnutrition.

PMID- 30298061
TI  - Microbial Changes and Host Response in F344 Rat Colon Depending on Sex and Age
      Following a High-Fat Diet.
AB  - Gut microbiota, an important component that affects host health, change rapidly
      and directly in response to altered diet composition. Recently, the role of diet
      microbiome interaction on the development of colon cancer has been the focus of
      interest. Colon cancer occurs more frequently in an aged population, and in
      males. However, the effect of dietary changes on the gut microbiome has been
      studied mainly in young males, even though it may vary with age and sex. The aim
      of this study was to investigate microbial changes and host response in the
      colons of male and female 6-week-old (young) and 2-year-old (old) Fisher-344 rats
      exposed to a high-fat diet (HFD). Our results showed that exposure to HFD for 8
      weeks decreased the species richness of microbiota (Chao1) and increased
      Firmicutes/Bacteroidetes ratio only in aged rats, and not in young rats. Sex
      differences underlying the alteration by HFD in the gut microbiome were observed
      in the microbiome of aged rats. For instance, the abundance ratio of Akkermansia
      muciniphila and Desulfovibrio spp. increased in response to HFD in young rats and
      female aged rats, but not in male aged rats. Histological inflammation and cell
      proliferation of colon mucosa (indexed by Ki67) were significantly increased by
      HFD even in young rats; aged rats showed significantly higher cell proliferation
      in the HFD group than in the control. The HFD-induced decrease of species
      richness and the increase in specific species (Desulfovibrio spp. and Clostridium
      lavalense), which produce carcinogenic compounds such as H2S and N-nitroso
      compounds, were significantly correlated with Ki67 index. In colon mucosa, the
      concentration of myeloperoxidase was increased by HFD only in males, and not in
      females. In conclusion, the results suggest a link between HFD-induced gut
      dysbiosis (particularly the low species richness and high abundance ratios of
      Desulfovibrio spp. and C. lavalense) and cell proliferation of colon mucosa
      (indicated by Ki67 IHC). In addition, sex differences influence the response of
      gut microbiome to HFD particularly in old age. Such sex differences in the gut
      microbiota might be related to sex differences in inflammation in the colon
      mucosa.

PMID- 30298062
TI  - MK2 Regulates Macrophage Chemokine Activity and Recruitment to Promote Colon
      Tumor Growth.
AB  - A major risk factor for colon cancer growth and progression is chronic
      inflammation. We have shown that the MAPK-activated protein kinase 2 (MK2)
      pathway is critical for colon tumor growth in colitis-associated and spontaneous
      colon cancer models. This pathway is known to regulate expression of the tumor
      promoting cytokines, IL-1, IL-6, and TNF-alpha. However, little is known about
      the ability of MK2 to regulate chemokine production. This is the first study to
      demonstrate this pathway also regulates the chemokines, MCP-1, Mip-1alpha, and
      Mip-2alpha (MMM). We show that these chemokines induce tumor cell growth and
      invasion in vitro and that MK2 inhibition suppresses tumor cell production of
      chemokines and reverses the resulting pro-tumorigenic effects. Addition of MMM to
      colon tumors in vivo significantly enhances tumor growth in control tumors and
      restores tumor growth in the presence of MK2 inhibition. We also demonstrate that
      MK2 signaling is critical for chemokine expression and macrophage influx to the
      colon tumor microenvironment. MK2 signaling in macrophages was essential for
      inflammatory cytokine/chemokine production, whereas MK2-/- macrophages or MK2
      inhibition suppressed cytokine expression. We show that addition of bone marrow
      derived macrophages to the tumor microenvironment enhances tumor growth in
      control tumors and restores tumor growth in tumors treated with MK2 inhibitors,
      while addition of MK2-/- macrophages had no effect. This is the first study to
      demonstrate the critical role of the MK2 pathway in chemokine production,
      macrophage influx, macrophage function, and tumor growth.

PMID- 30298065
TI  - Eliciting Dose and Safety Outcomes From a Large Dataset of Standardized Multiple
      Food Challenges.
AB  - Background: Food allergy prevalence has continued to rise over the past decade.
      While studies have reported threshold doses for multiple foods, large-scale multi
      food allergen studies are lacking. Our goal was to identify threshold dose
      distributions and predictors of severe reactions during blinded oral food
      challenges (OFCs) in multi-food allergic patients. Methods: A retrospective chart
      review was performed on all Stanford-initiated clinical protocols involving
      standardized screening OFCs to any of 11 food allergens at 7 sites. Interval
      censoring survival analysis was used to calculate eliciting dose (ED) curves for
      each food. Changes in severity and ED were also analyzed among participants who
      had repeated challenges to the same food. Results: Of 428 participants, 410 (96%)
      had at least one positive challenge (1445 standardized OFCs with 1054 total
      positive challenges). Participants undergoing peanut challenges had the highest
      ED50 (29.9 mg), while those challenged with egg or pistachio had the lowest (7.07
      or 1.7 mg, respectively). The most common adverse event was skin related (54%),
      followed by gastrointestinal (GI) events (33%). A history of asthma was
      associated with a significantly higher risk of a severe reaction (hazard ratio
      [HR]: 2.37, 95% confidence interval [CI]: 1.36, 4.13). Higher values of allergen
      specific IgE (sIgE) and sIgE to total IgE ratio (sIgEr) were also associated with
      higher risk of a severe reaction (1.49 [1.19, 1.85] and 1.84 [1.30, 2.59],
      respectively). Participants undergoing cashew, peanut, pecan, sesame, and walnut
      challenges had more severe reactions as ED increased. In participants who
      underwent repeat challenges, the ED did not change (p = 0.66), but reactions were
      more severe (p = 0.02). Conclusions: Participants with a history of asthma, high
      sIgEr, and/or high values of sIgE were found to be at higher risk for severe
      reactions during food challenges. These findings may help to optimize food
      challenge dosing schemes in multi-food allergic, atopic patients, specifically at
      lower doses where the majority of reactions occur. Trials Registration Number:
      ClinicalTrials. gov number NCT03539692;
      https://clinicaltrials.gov/ct2/show/NCT03539692.

PMID- 30298063
TI  - Positive & Negative Roles of Innate Effector Cells in Controlling Cancer
      Progression.
AB  - Innate immune cells are active at the front line of host defense against
      pathogens and now appear to play a range of roles under non-infectious conditions
      as well, most notably in cancer. Establishing the balance of innate immune
      responses is critical for the "flavor" of these responses and subsequent adaptive
      immunity and can be either "good or bad" in controlling cancer progression. The
      importance of innate NK cells in tumor immune responses has already been
      extensively studied over the last few decades, but more recently several
      relatively mono- or oligo-clonal [i.e., (semi-) invariant] innate T cell subsets
      received substantial interest in tumor immunology including invariant natural
      killer T (iNKT), gammadelta-T and mucosal associated invariant T (MAIT) cells.
      These subsets produce high levels of various pro- and/or anti-inflammatory
      cytokines/chemokines reflecting their capacity to suppress or stimulate immune
      responses. Survival of patients with cancer has been linked to the frequencies
      and activation status of NK, iNKT, and gammadelta-T cells. It has become clear
      that NK, iNKT, gammadelta-T as well as MAIT cells all have physiological roles in
      anti-tumor responses, which emphasize their possible relevance for tumor
      immunotherapy. A variety of clinical trials has focused on manipulating NK, iNKT,
      and gammadelta-T cell functions as a cancer immunotherapeutic approach
      demonstrating their safety and potential for achieving beneficial therapeutic
      effects, while the exploration of MAIT cell related therapies is still in its
      infancy. Current issues limiting the full therapeutic potential of these innate
      cell subsets appear to be related to defects and suppressive properties of these
      subsets that, with the right stimulus, might be reversed. In general, how innate
      lymphocytes are activated appears to control their subsequent abilities and
      consequent impact on adaptive immunity. Controlling these potent regulators and
      mediators of the immune system should enable their protective roles to dominate
      and their deleterious potential (in the specific context of cancer) to be
      mitigated.

PMID- 30298064
TI  - Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD):
      Toward a New Age.
AB  - Background: Among the many cannabinoids in the cannabis plant, cannabidiol (CBD)
      is a compound that does not produce the typical subjective effects of marijuana.
      Objectives: The aim of the present review is to describe the main advances in the
      development of the experimental and clinical use of cannabidiol CBD in
      neuropsychiatry. Methods: A non-systematic search was performed for studies
      dealing with therapeutic applications of CBD, especially performed by Brazilian
      researchers. Results: CBD was shown to have anxiolytic, antipsychotic and
      neuroprotective properties. In addition, basic and clinical investigations on the
      effects of CBD have been carried out in the context of many other health
      conditions, including its potential use in epilepsy, substance abuse and
      dependence, schizophrenia, social phobia, post-traumatic stress, depression,
      bipolar disorder, sleep disorders, and Parkinson. Discussion: CBD is an useful
      and promising molecule that may help patients with a number of clinical
      conditions. Controlled clinical trials with different neuropsychiatric
      populations that are currently under investigation should bring important answers
      in the near future and support the translation of research findings to clinical
      settings.

PMID- 30298067
TI  - Oncolytic Viruses Partner With T-Cell Therapy for Solid Tumor Treatment.
AB  - Adoptive T-cell immunotherapies, including chimeric antigen receptor-modified T
      cells (CAR-T cells), have revolutionized cancer treatment, especially for
      hematologic malignancies. Clinical success of CAR-T cell monotherapy in solid
      tumors however, has been only modest. Oncolytic viruses provide direct cancer
      cell lysis, stimulate systemic immune responses, and have the capacity to provide
      therapeutic transgenes. Oncolytic virotherapy has shown great promise in many
      preclinical solid tumor models and the first oncolytic virus has been approved by
      the FDA for the treatment of advanced melanoma. As monotherapies for solid
      tumors, oncolytic virotherapy provides only moderate anti-tumor effects. However,
      due to their complementary modes of action, oncolytic virus and T-cell therapies
      can be combined to overcome the inherent limitations of each agent. This review
      focuses on the aspects of oncolytic viruses that enable them to synergize with
      adoptive T-cell immunotherapies to enhance anti-tumor effects for solid tumors.

PMID- 30298066
TI  - Searching for the Transcriptomic Signature of Immune Tolerance Induction
      Biomarkers of Safety and Functionality for Tolerogenic Dendritic Cells and
      Regulatory Macrophages.
AB  - The last years have witnessed a breakthrough in the development of cell-based
      tolerance-inducing cell therapies for the treatment of autoimmune diseases and
      solid-organ transplantation. Indeed, the use of tolerogenic dendritic cells
      (tolDC) and regulatory macrophages (Mreg) is currently being tested in Phase I
      and Phase II clinical trials worldwide, with the aim of finding an effective
      therapy able to abrogate the inflammatory processes causing these pathologies
      without compromising the protective immunity of the patients. However, there
      exists a wide variety of different protocols to generate human tolDC and Mreg
      and, consequently, the characteristics of each product are heterogeneous. For
      this reason, the identification of biomarkers able to define their functionality
      (tolerogenicity) is of great relevance, on the one hand, to guarantee the safety
      of tolDC and Mreg before administration and, on the other hand, to compare the
      results between different cell products and laboratories. In this article, we
      perform an exhaustive review of protocols generating human tolDC and Mreg in the
      literature, aiming to elucidate if there are any common transcriptomic signature
      or potential biomarkers of tolerogenicity among the different approaches.
      However, and although several effectors seem to be induced in common in some of
      the most reported protocols to generate both tolDC or Mreg, the transcriptomic
      profile of these cellular products strongly varies depending on the approach used
      to generate them.

PMID- 30298069
TI  - ImmuneDB, a Novel Tool for the Analysis, Storage, and Dissemination of Immune
      Repertoire Sequencing Data.
AB  - ImmuneDB is a system for storing and analyzing high-throughput immune receptor
      sequencing data. Unlike most existing tools, which utilize flat-files, ImmuneDB
      stores data in a well-structured MySQL database, enabling efficient data queries.
      It can take raw sequencing data as input and annotate receptor gene usage, infer
      clonotypes, aggregate results, and run common downstream analyses such as
      calculating selection pressure and constructing clonal lineages. Alternatively,
      pre-annotated data can be imported and analyzed data can be exported in a variety
      of common Adaptive Immune Receptor Repertoire (AIRR) file formats. To validate
      ImmuneDB, we compare its results to those of another pipeline, MiXCR. We show
      that the biological conclusions drawn would be similar with either tool, while
      ImmuneDB provides the additional benefits of integrating other common tools and
      storing data in a database. ImmuneDB is freely available on GitHub at
      https://github.com/arosenfeld/immunedb, on PyPi at
      https://pypi.org/project/ImmuneDB, and a Docker container is provided at
      https://hub.docker.com/r/arosenfeld/immunedb. Full documentation is available at
      http://immunedb.com.

PMID- 30298070
TI  - Efficacy of Lactoferrin Oral Administration in the Treatment of Anemia and Anemia
      of Inflammation in Pregnant and Non-pregnant Women: An Interventional Study.
AB  - The discovery of the ferroportin-hepcidin complex has led to a critical review on
      the treatment of anemia and anemia of inflammation (AI). Ferroportin, the only
      known mammalian iron exporter from cells to blood, is negatively regulated by
      hepcidin, a hormone peptide able to bind to ferroportin, leading to its
      degradation. Therefore, new efficient therapeutic interventions acting on
      hepcidin and ferroportin are imperative to manage anemia and AI. Bovine milk
      derivative lactoferrin (bLf), a glycoprotein able to chelate two ferric ions per
      molecule, is emerging as a natural anti-inflammatory substance able to modulate
      hepcidin and ferroportin synthesis through the down-regulation of interleukin-6
      (IL-6). Here, an interventional study (ClinicalTrials.gov Identifier:
      NCT01221844) was conducted by orally administering 100 mg of 20-30% iron
      saturated bLf (corresponding to 70-84 MUg of elemental iron) twice a day. This
      treatment was compared with the Italian standard therapy, consisting in the oral
      administration of 329.7 mg of ferrous sulfate once a day (corresponding to 105 mg
      of elemental iron). Treatments were carried out on 29 anemic women with minor
      beta-thalassemia (20 pregnant and 9 non-pregnant), 149 women with hereditary
      thrombophilia (HT) (70 pregnant and 79 non-pregnant) affected by AI and 20 anemic
      pregnant women suffering from various pathologies. In anemic pregnant and non
      pregnant women with minor beta-thalassemia, presenting undetectable hepcidin
      levels, differently from ferrous sulfate management, bLf decreased IL-6 (from 25
      +/- 8 to 6 +/- 3 pg/ml) and increased total serum iron (TSI) (from 54 +/- 17 to
      80 +/- 9 MUg/dl). BLf was also more efficient than ferrous sulfate in AI
      treatment in HT pregnant and non-pregnant women by decreasing both serum IL-6
      (from 89 +/- 8 to 58 +/- 6 pg/ml) and hepcidin (from 115 +/- 23 to 65 +/- 10
      ng/ml), thus increasing hematological parameters, such as the number of red blood
      cells (RBCs), the concentration of hemoglobin, TSI and serum ferritin. BLf was
      also efficient in treating anemia in other pathological pregnancies. Taken
      together all the results, bLf, showing a greater benefit and efficacy than the
      standard ferrous sulfate management, can be considered as a promising compound in
      treating anemia and AI through its ability to down-regulate IL-6, thus restoring
      ferroportin-mediated iron export from cells to blood in a hepcidin-dependent or
      independent way.

PMID- 30298068
TI  - Tissue-Resident Lymphocytes Across Innate and Adaptive Lineages.
AB  - Lymphocytes are an integral component of the immune system. Classically, all
      lymphocytes were thought to perpetually recirculate between secondary lymphoid
      organs and only traffic to non-lymphoid tissues upon activation. In recent years,
      a diverse family of non-circulating lymphocytes have been identified. These
      include innate lymphocytes, innate-like T cells and a subset of conventional T
      cells. Spanning the innate-adaptive spectrum, these tissue-resident lymphocytes
      carry out specialized functions and cross-talk with other immune cell types to
      maintain tissue integrity and homeostasis both at the steady state and during
      pathological conditions. In this review, we provide an overview of the
      heterogeneous tissue-resident lymphocyte populations, discuss their development,
      and highlight their functions both in the context of microbial infection and
      cancer.

PMID- 30298072
TI  - Prophylactic Treatment With Simvastatin Modulates the Immune Response and
      Increases Animal Survival Following Lethal Sepsis Infection.
AB  - Chronic use of statins may have anti-inflammatory action, promoting
      immunomodulation and survival in patients with sepsis. This study aimed to
      analyze the effects of pretreatment with simvastatin in lethal sepsis induced by
      cecal ligation and puncture (CLP). Male Swiss mice received prophylactic
      treatment with simvastatin or pyrogen-free water orally in a single daily dose
      for 30 days. After this period, the CLP was performed. Naive and Sham groups were
      performed as non-infected controls. Animal survival was monitored for 60 h after
      the CLP. Half of mice were euthanized after 12 h to analyze colony-forming units
      (CFUs); hematological parameters; production of IL-10, IL-12, IL-6, TNF-alpha,
      IFN-gamma, and MCP-1; cell counts on peritoneum, bronchoalveolar lavage (BAL),
      bone marrow, spleen, and mesenteric lymph node; immunephenotyping of T cells and
      antigen presenting cells and production of hydrogen peroxide (H2O2). Simvastatin
      induced an increase in survival and a decrease in the CFU count on peritoneum and
      on BAL cells number, especially lymphocytes. There was an increase in the
      platelets and lymphocytes number in the Simvastatin group when compared to the
      CLP group. Simvastatin induced a greater activation and proliferation of CD4+ T
      cells, as well as an increase in IL-6 and MCP-1 production, in chemotaxis to the
      peritoneum and in H2O2 secretion at this site. These data suggest that
      simvastatin has an impact on the survival of animals, as well as immunomodulatory
      effects in sepsis induced by CLP in mice.

PMID- 30298071
TI  - Host-Parasite Interactions Promote Disease Tolerance to Intestinal Helminth
      Infection.
AB  - Parasitic helminths are among the most pervasive pathogens of the animal kingdom.
      To complete their life cycle, these intestinal worms migrate through host tissues
      causing significant damage in their wake. As a result, infection can lead to
      malnutrition, anemia and increased susceptibility to co-infection. Despite
      repeated deworming treatment, individuals living in endemic regions remain highly
      susceptible to re-infection by helminths, but rarely succumb to excessive tissue
      damage. The chronicity of infection and inability to resist numerous species of
      parasitic helminths that have co-evolved with their hosts over millenia suggests
      that mammals have developed mechanisms to tolerate this infectious disease.
      Distinct from resistance where the goal is to destroy and eliminate the pathogen,
      disease tolerance is an active process whereby immune and structural cells
      restrict tissue damage to maintain host fitness without directly affecting
      pathogen burden. Although disease tolerance is evolutionary conserved and has
      been well-described in plant systems, only recently has this mode of host
      defense, in its strictest sense, begun to be explored in mammals. In this review,
      we will examine the inter- and intracellular networks that support disease
      tolerance during enteric stages of parasitic helminth infection and why this
      alternative host defense strategy may have evolved to endure the presence of non
      replicating pathogens and maintain the essential functions of the intestine.

PMID- 30298073
TI  - Leptin Elicits LTC4 Synthesis by Eosinophils Mediated by Sequential Two-Step
      Autocrine Activation of CCR3 and PGD2 Receptors.
AB  - Leptin is a cytokine, produced mainly by mature adipocytes, that regulates the
      central nervous system, mainly to suppress appetite and stimulate energy
      expenditure. Leptin also regulates the immune response by controlling activation
      of immunomodulatory cells, including eosinophils. While emerging as immune
      regulatory cells with roles in adipose tissue homeostasis, eosinophils have a
      well-established ability to synthesize pro-inflammatory molecules such as lipid
      mediators, a key event in several inflammatory pathologies. Here, we investigated
      the impact and mechanisms involved in leptin-driven activation of eicosanoid
      synthesizing machinery within eosinophils. Direct in vitro activation of human or
      mouse eosinophils with leptin elicited synthesis of lipoxygenase as well as
      cyclooxygenase products. Displaying selectivity, leptin triggered synthesis of
      LTC4 and PGD2, but not PGE2, in parallel to dose-dependent induction of lipid
      body/lipid droplets biogenesis. While dependent on PI3K activation, leptin-driven
      eosinophil activation was also sensitive to pertussis toxin, indicating the
      involvement of G-protein coupled receptors on leptin effects. Leptin-induced
      lipid body-driven LTC4 synthesis appeared to be mediated through autocrine
      activation of G-coupled CCR3 receptors by eosinophil-derived CCL5, inasmuch as
      leptin was able to trigger rapid CCL5 secretion, and neutralizing anti-RANTES or
      anti-CCR3 antibodies blocked lipid body assembly and LTC4 synthesis induced by
      leptin. Remarkably, autocrine activation of PGD2 G-coupled receptors DP1 and DP2
      also contributes to leptin-elicited lipid body-driven LTC4 synthesis by
      eosinophils in a PGD2-dependent fashion. Blockade of leptin-induced PGD2
      autocrine/paracrine activity by a specific synthesis inhibitor or DP1 and DP2
      receptor antagonists, inhibited both lipid body biogenesis and LTC4 synthesis
      induced by leptin stimulation within eosinophils. In addition, CCL5-driven CCR3
      activation appears to precede PGD2 receptor activation within eosinophils, since
      neutralizing anti-CCL5 or anti-CCR3 antibodies inhibited leptin-induced PGD2
      secretion, while it failed to alter PGD2-induced LTC4 synthesis. Altogether,
      sequential activation of CCR3 and then PGD2 receptors by autocrine ligands in
      response to leptin stimulation of eosinophils culminates with eosinophil
      activation, characterized here by assembly of lipidic cytoplasmic platforms
      synthesis and secretion of the pleiotropic lipid mediators, PGD2, and LTC4.

PMID- 30298074
TI  - Genome-Wide Identification and Expression Profiling of the TCP Family Genes in
      Spike and Grain Development of Wheat (Triticum aestivum L.).
AB  - The TCP family genes are plant-specific transcription factors and play important
      roles in plant development. TCPs have been evolutionarily and functionally
      studied in several plants. Although common wheat (Triticum aestivum L.) is a
      major staple crop worldwide, no systematic analysis of TCPs in this important
      crop has been conducted. Here, we performed a genome-wide survey in wheat and
      found 66 TCP genes that belonged to 22 homoeologous groups. We then mapped these
      genes on wheat chromosomes and found that several TCP genes were duplicated in
      wheat including the ortholog of the maize TEOSINTE BRANCHED 1. Expression study
      using both RT-PCR and in situ hybridization assay showed that most wheat TCP
      genes were expressed throughout development of young spike and immature seed. Cis
      acting element survey along promoter regions suggests that subfunctionalization
      may have occurred for homoeologous genes. Moreover, protein-protein interaction
      experiments of three TCP proteins showed that they can form either homodimers or
      heterodimers. Finally, we characterized two TaTCP9 mutants from tetraploid wheat.
      Each of these two mutant lines contained a premature stop codon in the A
      subgenome homoeolog that was dominantly expressed over the B subgenome homoeolog.
      We observed that mutation caused increased spike and grain lengths. Together, our
      analysis of the wheat TCP gene family provides a start point for further
      functional study of these important transcription factors in wheat.

PMID- 30298076
TI  - Targeted Metabolic Profiling Indicates Apple Rootstock Genotype-Specific
      Differences in Primary and Secondary Metabolite Production and Validate
      Quantitative Contribution From Vegetative Growth.
AB  - Previous reports regarding rhizodeposits from apple roots are limited, and
      complicated by microbes, which readily colonize root systems and contribute to
      modify rhizodeposit metabolite composition. This study delineates methods for
      collection of apple rhizodeposits under axenic conditions, indicates rootstock
      genotype-specific differences and validates the contributions of vegetative
      activity to rhizodeposit quantity. Primary and phenolic rhizodeposit metabolites
      collected from two apple rootstock genotypes, G935 and M26, were delineated 2
      months after root initiation by utilizing gas chromatography/liquid
      chromatography-mass spectrometry (GC/LC-MS), respectively. Twenty-one identified
      phenolic compounds and 29 sugars, organic acids, and amino acids, as well as
      compounds tentatively identified as triterpenoids were present in the
      rhizodeposits. When adjusted for whole plant mass, hexose, erythrose, galactose,
      phloridzin, kaempferol-3-glucoside, as well as glycerol, and glyceric acid
      differed between the genotypes. Phloridzin, phloretin, epicatechin, 4
      hydroxybenzoic acid, and chlorogenic acid were among the phenolic compounds found
      in higher relative concentration in rhizodeposits, as assessed by LC-MS. Among
      primary metabolites assessed by GC-MS, amino acids, organic acids, and sugar
      alcohols found in relatively higher concentration in the rhizodeposits included L
      asparagine, L-cysteine, malic acid, succinic acid, and sorbitol. In addition,
      putative ursane triterprenoids, identified based on accurate mass comparison to
      previously reported triterpenoids from apple peel, were present in rhizodeposits
      in high abundance relative to phenolic compounds assessed via the same
      extraction/instrumental method. Validation of metabolite production to tree
      vegetative activity was conducted using a separate set of micropropagated trees
      (genotype MM106) which were treated with a toxic volatile compound
      (butyrolactone) to inhibit activity/kill leaves and vegetative growth. This
      treatment resulted in a reduction of total collected rhizodeposits relative to an
      untreated control, indicating active vegetative growth contributes to
      rhizodeposit metabolites. Culture-based assays indicated an absence of bacterial
      or fungal endophytes in roots of micropropagated G935 and M26 plants. However,
      the use of fungi-specific primers in qPCR indicated the presence of fungal DNA in
      30% of the samples, thus the contribution of endophytes to rhizodeposits cannot
      be fully eliminated. This study provides fundamental information for continued
      research and application of rhizosphere ecology driven by apple rootstock
      genotype specific rhizodeposition.

PMID- 30298075
TI  - Usefulness of a New Large Set of High Throughput EST-SNP Markers as a Tool for
      Olive Germplasm Collection Management.
AB  - Germplasm collections are basic tools for conservation, characterization, and
      efficient use of olive genetic resources. The identification of the olive
      cultivars maintained in the collections is an important ongoing task which has
      been performed by both, morphological and molecular markers. In the present
      study, based on the sequencing results of previous genomic projects, a new set of
      1,043 EST-SNP markers has been identified. In order to evaluate its
      discrimination capacity and utility in diversity studies, this set of markers was
      used in a representative number of accessions from 20 different olive growing
      countries and maintained at the World Olive Germplasm Collection of IFAPA Centre
      'Alameda del Obispo' (Cordoba, Spain), one of the world's largest olive germplasm
      bank. Thus, the cultivated material included: cultivars belonging to previously
      defined core collections by means of SSR markers and agronomical traits, well
      known homonymy cases, possible redundancies previously identified in the
      collection, and recently introduced accessions. Marker stability was tested in
      repeated analyses of a selected number of accessions, as well as in different
      trees and accessions belonging to the same cultivar. In addition, 15 genotypes
      from a cross 'Picual' * 'Arbequina' cultivars from the IFAPA olive breeding
      program and a set of 89 wild genotypes were also included in the study. Our
      results indicate that, despite their relatively wide variability, the new set of
      EST-SNPs displayed lower levels of genetic diversity than SSRs in the set of
      olive core collections tested. However, the EST-SNP markers displayed consistent
      and reliable results from different plant material sources and plant propagation
      events. The EST-SNPs revealed a clear cut off between inter- and intra-cultivar
      variation in olive. Besides, they were able to reliably discriminate among
      different accessions, to detect possible homonymy cases as well as efficiently
      ascertain the presence of redundant germplasm in the collection. Additionally,
      these markers were highly transferable to the wild genotypes. These results,
      together with the low genotyping error rates and the easy and fully automated
      procedure used to get the genotyping data, validate the new set of EST-SNPs as
      possible markers of choice for olive cultivar identification.

PMID- 30298077
TI  - Use of Biostimulants for Organic Apple Production: Effects on Tree Growth, Yield,
      and Fruit Quality at Harvest and During Storage.
AB  - The experiment was conducted during two consecutive seasons (years 2016 and 2017)
      in an organic apple orchard of the cultivar Jonathan. Several biostimulants were
      tested (10 in total), including humic acids, macro and micro seaweed extracts,
      alfalfa protein hydrolysate, amino acids alone or in combination with zinc, B
      group vitamins, chitosan and a commercial product containing silicon. Treatments
      were performed at weekly intervals, starting from the end of May until mid
      August. The macroseaweed extract was effective in stimulate tree growth potential
      in both years, as shown by a significantly larger leaf area (+20% as compared to
      control) and by an higher chlorophyll content and leaf photosynthetic rate in
      year 2016. As for the yield performances and apples quality traits at harvest
      (average fruit weight, soluble solids content, titratable acidity, and flesh
      firmness), they were generally affected by the different climatic conditions that
      characterized the two growing seasons (year 2017 being characterized by higher
      maximal and average temperatures and by limited rainfalls at the beginning of the
      season). Treatments with macroseaweed extract, B-group vitamins and alfalfa
      protein hydrolysate were able to significantly improve the intensity and
      extension of the red coloration of apples at harvest. Correspondingly, the
      anthocyanin content in the skin of apples treated with the same biostimulants
      resulted significantly higher than control, highlighting the potential influence
      of these substances on the synthesis of secondary metabolites in apple. The
      incidence of physiological disorders was also monitored during apple storage
      period. Amino acids plus zinc application was effective in reducing (more than
      50%) the incidence of the "Jonathan spot," the main post-harvest disorder for
      this cultivar.

PMID- 30298078
TI  - Redox Regulation of Starch Metabolism.
AB  - Metabolism of starch is a major biological integrator of plant growth supporting
      nocturnal energy dynamics by transitory starch degradation as well as periods of
      dormancy, re-growth, and reproduction by utilization of storage starch.
      Especially, the extraordinarily well-tuned and coordinated rate of transient
      starch biosynthesis and degradation suggests the presence of very sophisticated
      regulatory mechanisms. Together with the circadian clock, land plants (being
      autotrophic and sessile organisms) need to monitor, sense, and recognize the
      photosynthetic rate, soil mineral availability as well as various abiotic and
      biotic stress factors. Currently it is widely accepted that post-translational
      modifications are the main way by which the diel periodic activity of enzymes of
      transient starch metabolism are regulated. Among these mechanisms, thiol-based
      redox regulation is suggested to be of fundamental importance and in
      chloroplasts, thioredoxins (Trx) are tightly linked up to photosynthesis and
      mediate light/dark regulation of metabolism. Also, light independent NADP
      thioredoxin reductase C (NTRC) plays a major role in reactive oxygen species
      scavenging. Moreover, Trx and NTRC systems are interconnected at several levels
      and strongly influence each other. Most enzymes involved in starch metabolism are
      demonstrated to be redox-sensitive in vitro. However, to what extent their redox
      sensitivity is physiologically relevant in synchronizing starch metabolism with
      photosynthesis, heterotrophic energy demands, and oxidative protection is still
      unclear. For example, many hydrolases are activated under reducing (light)
      conditions and the strict separation between light and dark metabolic pathways is
      now challenged by data suggesting degradation of starch during the light period.

PMID- 30298079
TI  - Dual or Not Dual?-Comparative Analysis of Fluorescence Microscopy-Based
      Approaches to Study Organelle Targeting Specificity of Nuclear-Encoded Plant
      Proteins.
AB  - Plant cells are unique as they carry two organelles of endosymbiotic origin,
      namely mitochondria and chloroplasts (plastids) which have specific but partially
      overlapping functions, e. g., in energy and redox metabolism. Despite housing
      residual genomes of limited coding capacity, most of their proteins are encoded
      in the nucleus, synthesized by cytosolic ribosomes and need to be transported
      "back" into the respective target organelle. While transport is in most instances
      strictly monospecific, a group of proteins carries "ambiguous" transit peptides
      mediating transport into both, mitochondria and plastids. However, such dual
      targeting is often disputed due to variability in the results obtained from
      different experimental approaches. We have therefore compared and evaluated the
      most common methods established to study protein targeting into organelles within
      intact plant cells. All methods are based on fluorescent protein technology and
      live cell imaging. For our studies, we have selected four candidate proteins with
      proven dual targeting properties and analyzed their subcellular localization in
      vivo utilizing four different methods (particle bombardment, protoplast
      transformation, Agrobacterium infiltration, and transgenic plants). Though using
      identical expression constructs in all instances, a given candidate protein does
      not always show the same targeting specificity in all approaches, demonstrating
      that the choice of method is important, and depends very much on the question to
      be addressed.

PMID- 30298080
TI  - Overexpression of a NF-YC Gene Results in Enhanced Drought and Salt Tolerance in
      Transgenic Seashore Paspalum.
AB  - Seashore paspalum (Paspalum vaginatum O. Swartz) is an important warm-season
      turfgrass species. In this study we generated transgenic seashore paspalum
      overexpressing CdtNF-YC1, a nuclear factor Y transcription factor from hybrid
      bermudagrass (Cynodon dactylon * Cynodon transvaalensis). DNA blot hybridization
      and qRT-PCR analysis showed that CdtNF-YC1 was integrated into the genomes of
      transgenic seashore paspalum plants and expressed. Reduced relative water content
      (RWC) and survival rate and increased ion leakage were observed in both wild type
      (WT) and transgenic plants after drought stress, while transgenic plants had
      higher levels of RWC and survival rate and lower ion leakage than the WT. Maximal
      photochemical efficiency of photosystem II (F v/F m), chlorophyll concentration
      and survival rate were decreased after salt stress, while higher levels were
      maintained in transgenic plants than in WT. In addition, an increased Na+ content
      and decreased or unaltered K+ in leaves and roots were observed after salt
      treatment, while lower level of Na+ and higher levels of K+ and K+/ Na+ ratio
      were maintained in transgenic plants than in WT. The results indicated that
      overexpressing CdtNF-YC1 resulted in enhanced drought and salt tolerance in
      transgenic plants. Transcript levels of stress responsive genes including PvLEA3,
      PvP5CS1, PvABI2, and PvDREB1B were induced in response to drought and salt
      stress, and higher levels were observed in transgenic seashore paspalum than in
      WT. The results suggest that the enhanced drought and salt tolerance in
      transgenic seashore paspalum is associated with induction of a series of stress
      responsive genes as a result of overexpression of CdtNF-YC1.

PMID- 30298081
TI  - Rapeseed Seedling Stand Counting and Seeding Performance Evaluation at Two Early
      Growth Stages Based on Unmanned Aerial Vehicle Imagery.
AB  - The development of unmanned aerial vehicles (UAVs) and image processing
      algorithms for field-based phenotyping offers a non-invasive and effective
      technology to obtain plant growth traits such as canopy cover and plant height in
      fields. Crop seedling stand count in early growth stages is important not only
      for determining plant emergence, but also for planning other related agronomic
      practices. The main objective of this research was to develop practical and rapid
      remote sensing methods for early growth stage stand counting to evaluate
      mechanically seeded rapeseed (Brassica napus L.) seedlings. Rapeseed was seeded
      in a field by three different seeding devices. A digital single-lens reflex
      camera was installed on an UAV platform to capture ultrahigh resolution RGB
      images at two growth stages when most rapeseed plants had at least two leaves.
      Rapeseed plant objects were segmented from images of vegetation indices using
      typical Otsu thresholding method. After segmentation, shape features such as
      area, length-width ratio and elliptic fit were extracted from the segmented
      rapeseed plant objects to establish regression models of seedling stand count.
      Three row characteristics (the coefficient of variation of row spacing
      uniformity, the error rate of the row spacing and the coefficient of variation of
      seedling uniformity) were further calculated for seeding performance evaluation
      after crop row detection. Results demonstrated that shape features had strong
      correlations with ground-measured seedling stand count. The regression models
      achieved R-squared values of 0.845 and 0.867, respectively, for the two growth
      stages. The mean absolute errors of total stand count were 9.79 and 5.11% for the
      two respective stages. A single model over these two stages had an R-squared
      value of 0.846, and the total number of rapeseed plants was also accurately
      estimated with an average relative error of 6.83%. Moreover, the calculated row
      characteristics were demonstrated to be useful in recognizing areas of failed
      germination possibly resulted from skipped or ineffective planting. In summary,
      this study developed practical UAV-based remote sensing methods and demonstrated
      the feasibility of using the methods for rapeseed seedling stand counting and
      mechanical seeding performance evaluation at early growth stages.

PMID- 30298082
TI  - Discovering Causal Relationships in Grapevine Expression Data to Expand Gene
      Networks. A Case Study: Four Networks Related to Climate Change.
AB  - In recent years the scientific community has been heavily engaged in studying the
      grapevine response to climate change. Final goal is the identification of key
      genetic traits to be used in grapevine breeding and the setting of agronomic
      practices to improve climatic resilience. The increasing availability of
      transcriptomic studies, describing gene expression in many tissues and
      developmental, or treatment conditions, have allowed the implementation of gene
      expression compendia, which enclose a huge amount of information. The mining of
      transcriptomic data represents an effective approach to expand a known local gene
      network (LGN) by finding new related genes. We recently published a pipeline
      based on the iterative application of the PC-algorithm, named NES2RA, to expand
      gene networks in Escherichia coli and Arabidopsis thaliana. Here, we propose the
      application of this method to the grapevine transcriptomic compendium Vespucci,
      in order to expand four LGNs related to the grapevine response to climate change.
      Two networks are related to the secondary metabolic pathways for anthocyanin and
      stilbenoid synthesis, involved in the response to solar radiation, whereas the
      other two are signaling networks, related to the hormones abscisic acid and
      ethylene, possibly involved in the regulation of cell water balance and cuticle
      transpiration. The expansion networks produced by NES2RA algorithm have been
      evaluated by comparison with experimental data and biological knowledge on the
      identified genes showing fairly good consistency of the results. In addition, the
      algorithm was effective in retaining only the most significant interactions among
      the genes providing a useful framework for experimental validation. The
      application of the NES2RA to Vitis vinifera expression data by means of the BOINC
      based implementation is available upon request (valter.cavecchia@cnr.it).

PMID- 30298083
TI  - Spatial Patterns of Leaf Carbon, Nitrogen, and Phosphorus Stoichiometry of
      Aquatic Macrophytes in the Arid Zone of Northwestern China.
AB  - Ecological stoichiometry is a powerful indicator for understanding the adaptation
      of plants to environment. However, understanding of stoichiometric
      characteristics of leaf carbon (C%), nitrogen (N%), and phosphorus (P%) for
      aquatic macrophytes remains limited. In this study, 707 samples from 146 sites
      were collected to study the variations in leaf C%, N%, and P%, and tried to
      explore how different environmental conditions affect leaf C, N, and P
      stoichiometry. Results showed that the mean values of leaf C%, N%, P%, and N:P
      ratios were 39.95%, 2.12%, 0.14%, and 16.60% of macrophytes across the arid zone
      of northwestern China, respectively. And the mean values of leaf P% were lower
      than those from the Tibetan Plateau and eastern China, which maybe due to an
      adaptation strategy of the plants to the unique conditions in the arid zone in
      the long-term evolutionary process. The higher N:P ratios suggested that P was
      established as the limiting factor of the macrophytes communities in the arid
      zone of northwestern China. There were significant differences in leaf C%, N%,
      P%, and their ratios among different life forms. Our results also showed strong
      relationships between leaf N% and N:P ratios and longitude, leaf N%, P%, and N:P
      ratios and latitude, and leaf N% and P% and altitude, respectively. In addition,
      the results showed that pH can significantly influence leaf C%. Our results
      supported the temperature-plant physiology hypothesis owing to a negative
      relationship between leaf N% and P% of macrophytes and mean annual temperature in
      the arid zone of northwestern China. The different patterns of leaf stoichiometry
      between the arid zone of northwestern China and eastern China indicated that
      there were different physiological and ecological adaptability of macrophytes to
      environmental gradients in different climatic zones.

PMID- 30298084
TI  - The Phytogeographic History of Common Walnut in China.
AB  - Common walnut (Juglans regia L.) is an economically important hardwood tree
      species cultivated worldwide for its high quality wood and edible nuts. It is
      generally accepted that after the last glaciation J. regia survived and grew in
      almost completely isolated stands in Asia, and that ancient humans dispersed
      walnuts across Asia and into new habitats via trade and cultural expansion. The
      history of common walnut in China is a matter of debate, however. We estimated
      the genetic diversity and spatial genetic structure of 31 walnut populations
      sampled across its Chinese range using 22 microsatellite markers (13 neutral and
      9 non-neutral). Using historical data and population genetic analysis, including
      approximate Bayesian analysis (ABC), we reconstructed the demographic history of
      J. regia in China. The genetic data indicated the likely presence of J. regia in
      glacial refugia in the Xinjiang province (Northwest China), Northeastern China
      (Beijing, Shandong, and Changbai Mountains), Central China (Qinling and Baishan
      Mountains and Xi'an), and Southwestern China (Tibet, Yunnan, Guizhou, and Sichuan
      provinces). Based on DIY-ABC analysis, we identified three ancient lineages of J.
      regia in China. Two lineages (subpopulation A and subpopulation B+C) diverged
      about 2.79 Mya, while Southwestern China, and Qinling and Baishan Mountains
      lineages diverged during the Quaternary glaciations (about 1.13 Mya). Remnants of
      these once-distinct genetic clusters of J. regia may warrant ecological
      management if they are to be retained as in situ resources. A population size
      expansion in Northeastern China was detected in the last five centuries. The
      present distribution of walnut in China resulted from the combined effects of
      expansion/contraction from multiple refugia after the Last Glacial Maximum and
      later human exploitation.

PMID- 30298085
TI  - The Current Status and Development of Insect-Resistant Genetically Engineered
      Poplar in China.
AB  - Poplar is one of the main afforestation tree species in China, and the use of a
      single, or only a few, clones with low genetic diversity in poplar plantations
      has led to increasing problems with insect pests. The use of genetic engineering
      to cultivate insect-resistant poplar varieties has become a hot topic. Over the
      past 20 years, there have been remarkable achievements in this area. To date,
      nearly 22 insect-resistant poplar varieties have been created and approved for
      small-scale field testing, environmental release, or pilot-scale production.
      Here, we comprehensively review the development of insect-resistant genetically
      modified (GM) poplars in China. This review mostly addresses issues surrounding
      the regulation and commercialization of Bt poplar in China, the various
      insecticidal genes used, the effects of transgenic poplars on insects, toxic
      protein expression, multigene transformation, the stability of insect resistance,
      and biosafety. The efficacy of GM poplars for pest control differed among
      different transgenic poplar clones, larval instars, and insect species. The Bt
      protein analysis revealed that the expression level of Cry3A was significantly
      higher than that of Cry1Ac. Temporal and spatial studies of Bt protein showed
      that its expression varied with the developmental stage and tissue. The
      inheritance and expression of the exogenous gene were reviewed in transgenic
      hybrid poplar progeny lines and grafted sections. Biosafety issues, in terms of
      transgene stability and the effects on soil microorganisms, natural enemies of
      insects, and arthropod communities are also discussed.

PMID- 30298086
TI  - Intracytoplasmic Re-localization of miRISC Complexes.
AB  - MicroRNAs (miRNAs) are a conserved class of non-coding RNAs of 22 nucleotides
      that post-transcriptionally regulate gene expression through translational
      repression and/or mRNA degradation. A great progress has been made regarding
      miRNA biogenesis and miRNA-mediated gene regulation. Additionally, an ample
      amount of information exists with respect to the regulation of miRNAs. However,
      the cytoplasmic localization of miRNAs and its effect on gene regulatory output
      is still in progress. We provide a current review of the cytoplasmic miRNA
      localization in metazoans. We then discuss the dynamic changes in the
      intracytoplasmic localization of miRNAs as a means to regulate their silencing
      activity. We then conclude our discussion with the potential molecules that could
      modulate miRNA localization.

PMID- 30298088
TI  - Medical Image Classification Based on Deep Features Extracted by Deep Model and
      Statistic Feature Fusion with Multilayer Perceptron?.
AB  - Medical image classification is a key technique of Computer-Aided Diagnosis (CAD)
      systems. Traditional methods rely mainly on the shape, color, and/or texture
      features as well as their combinations, most of which are problem-specific and
      have shown to be complementary in medical images, which leads to a system that
      lacks the ability to make representations of high-level problem domain concepts
      and that has poor model generalization ability. Recent deep learning methods
      provide an effective way to construct an end-to-end model that can compute final
      classification labels with the raw pixels of medical images. However, due to the
      high resolution of the medical images and the small dataset size, deep learning
      models suffer from high computational costs and limitations in the model layers
      and channels. To solve these problems, in this paper, we propose a deep learning
      model that integrates Coding Network with Multilayer Perceptron (CNMP), which
      combines high-level features that are extracted from a deep convolutional neural
      network and some selected traditional features. The construction of the proposed
      model includes the following steps. First, we train a deep convolutional neural
      network as a coding network in a supervised manner, and the result is that it can
      code the raw pixels of medical images into feature vectors that represent high
      level concepts for classification. Second, we extract a set of selected
      traditional features based on background knowledge of medical images. Finally, we
      design an efficient model that is based on neural networks to fuse the different
      feature groups obtained in the first and second step. We evaluate the proposed
      approach on two benchmark medical image datasets: HIS2828 and ISIC2017. We
      achieve an overall classification accuracy of 90.1% and 90.2%, respectively,
      which are higher than the current successful methods.

PMID- 30298090
TI  - Outcomes Following Salvage Radiation and Systemic Therapy for Isolated
      Locoregional Recurrence of Breast Cancer after Mastectomy: Impact of Constructed
      Biologic Subtype.
AB  - Purpose: This study examines factors associated with outcomes following salvage
      radiation and systemic therapy for breast cancer patients who developed isolated
      locoregional recurrence (ILRR) after mastectomy alone, while focusing on the
      prognostic significance of constructed biologic subtype in this setting. Methods
      and Materials: 269 postmastectomy patients in total treated for ILRR were
      included. Cumulative incidence of locoregional control (LRC), distant metastasis
      (DM)-free survival (DMFS), disease-free survival (DFS), and overall survival (OS)
      were calculated using Kaplan-Meier method. For statistical analysis, biologic
      subtypes were constructed from hormonal receptors (Rec) and HER2, consisting of
      Rec+/HER2-, Rec+/HER2+, Rec-/HER2+, and Rec-/HER2-. The association of clinic
      pathological and treatment-related parameters with outcomes was evaluated using a
      Cox regression model. Results: At a median follow-up of 65 months, 56 (20.8%)
      patients failed to secure LRC after radiotherapy, and 165 patients (61.3%)
      developed DM. Overall, the actuarial 5-year LRC, DMFS, DFS, and OS rate was
      77.3%, 45.6%, 43.9%, and 66.8%, respectively. Multivariate analysis revealed that
      constructed biologic subtype represented the most significant prognostic factor
      for any outcome. Compared to patients with Rec+/HER2- disease, those with Rec
      /HER2- had significantly poorer 5-year LRC (84.2% versus 58.3%, HR = 4.36, P <
      0.001) and worse survivals including 5-year DMFS (63.0% versus 15.8%, HR = 4.28,
      P < 0.001), DFS (59.7% versus 13.6%, HR=3.92, P < 0.001), and OS (87.8% versus
      22.3%, HR = 8.55, P < 0.001). Other factors associated with reduced LRC were no
      radical surgery and involved field irradiation alone, whereas factors associated
      with poor survivals included positive nodes at primary diagnosis and regional
      recurrence. Conclusions: Constructed biologic subtypes remained to be predictive
      of both disease control and survivals after salvage radiation for postmastectomy
      ILRR. Notably, Rec-/HER2- patients were demonstrated to be at high risk of
      locoregional failure and subsequent DM and tended to have worse survivals despite
      salvage therapies.

PMID- 30298089
TI  - Laparoscopic Spleen-Preserving Distal Pancreatectomy (LSPDP) with Preservation of
      Splenic Vessels: An Inferior-Posterior Approach.
AB  - Objective: To summarize the operation experience of laparoscopic spleen
      preserving distal pancreatectomy (LSPDP) with preservation of splenic vessels by
      an inferior-posterior dissection of the pancreatic body and evaluate its
      feasibility. Methods: Patients undergoing LSPDS at Ningbo Li Huili Hospital and
      Ningbo Li Huili Eastern Hospital from January 2014 to April 2017 were recruited
      in this study and were analyzed retrospectively. They were divided into two
      groups based on the surgical approach: the inferior-posterior approach group and
      the other approach group. We sought to compare outcomes of the two groups.
      Results: The LSPDP procedure was completed successfully in 49 cases, and 48
      patients had their splenic artery and vein preserved, including 26 cases in the
      inferior-posterior approach group and 22 cases in the other approach group. There
      were no significant differences between the two groups with respect to age (p =
      0.18), sex (p = 0.56), preoperative diabetes (p = 1.00), ASA grading (p = 1.00),
      tumor size (p = 0.91), intraoperative blood loss (t = -0.01, p = 0.99), hospital
      stay (t = -0.02, p = 0.98), and pancreatic fistula rates (p = 1.00). Patients
      undergoing LSPDP by the inferior-posterior approach had a shorter operative time
      (t = -4.13, p < 0.001) than the other approach group. Conclusions: LSPDS by the
      inferior-posterior approach associated with shorter operative time is safe and
      feasible.

PMID- 30298091
TI  - Knowledge, Attitudes, and Practices on Infection Control Measures in Stomatology
      Students in Lima, Peru.
AB  - Introduction: The level of knowledge, attitudes, and practices with respect to
      infection control measures in undergraduate stomatology students is not well
      understood; that is why these variables were evaluated in the students of the
      Universidad Privada San Juan Bautista between September and November of 2017.
      Methods: A cross-sectional study was carried out. A total of 347 students from
      the Ica, Lima Norte, and Chorrillos campuses were evaluated. The sample was
      calculated using the statistical formula of comparison of means. The
      questionnaire of the CDC (Center of Contagious Diseases) was used to measure the
      variables described. Results: It was observed that 72.05% of the students
      preferred to use oral rinsing before starting a treatment, 72.62% used the
      autoclave as the primary equipment to sterilize their instruments in the dental
      clinic, 95.10% considered that isolation is important in the control of the
      infection, 46.40% affirmed that tuberculosis is the most infectious disease, and
      only 26.51% considered it to be hepatitis B. On the other hand, it was found that
      the scores of knowledge, attitudes, and practices were 2.74 +/- 2.16, 3.59 +/-
      0.88, and 3.59 +/- 1.73, respectively. Conclusions: The level of knowledge was
      low among the students evaluated; however, as far as the level of practices and
      attitudes was high, even so, this topic must be reinforced so that stomatology
      students reflect on the importance of the risks that exist to get infected with
      any disease inside the dental office, as outside of it.

PMID- 30298087
TI  - De novo Mutations (DNMs) in Autism Spectrum Disorder (ASD): Pathway and Network
      Analysis.
AB  - Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder (NDD) defined by
      impairments in social communication and social interactions, accompanied by
      repetitive behavior and restricted interests. ASD is characterized by its
      clinical and etiological heterogeneity, which makes it difficult to elucidate the
      neurobiological mechanisms underlying its pathogenesis. Recently, de novo
      mutations (DNMs) have been recognized as strong source of genetic causality.
      Here, we review different aspects of the DNMs associated with ASD, including
      their functional annotation and classification. In addition, we also focus on the
      most recent advances in this area, such as the detection of PZMs (post-zygotic
      mutations), and we outline the main bioinformatics tools commonly employed to
      study these. Some of these approaches available allow DNMs to be analyzed in the
      context of gene networks and pathways, helping to shed light on the biological
      processes underlying ASD. To end this review, a brief insight into the future
      perspectives for genetic studies into ASD will be provided.

PMID- 30298092
TI  - Therapy of Dredging the Bowels Enhanced the Neuroprotective Effect of Nourishing
      Kidney Herbs on Hippocampal Cholinergic System in Alzheimer's Disease Model Rat
      Induced by Abeta 1-42.
AB  - Background: Therapy of nourishing kidney has been used for treating memory
      deficits of Alzheimer's disease (AD) for thousands of years based on traditional
      Chinese medicine. However, we found the therapy of dredging the bowels could
      alleviate both memory deficits and mental symptoms of AD in clinic. Objective: To
      determine whether the therapy of dredging the bowels could enhance the
      neuroprotective effect of nourishing kidney herbs for treating AD rats, and to
      explore the underlying mechanism of the combination of nourishing kidney and
      dredging the bowels (NKDB) herbs. Methods: 60 rats were randomly divided into
      sham-operated group (SOG), model group (MG), nourishing kidney group (NKG),
      dredging the bowels group (DBG), nourishing kidney and dredging the bowels group
      (NKDBG), and donepezil hydrochloride group (DHG). The model establishment was
      performed by injecting Abeta 1-42 into the hippocampal CA1 region. Animals
      received aqueous solution of Chinese herbal medicine or western medicine while
      SOG received only distilled water. Ability of learning and memory were assessed
      by Morris water maze. Acetylcholinesterase(AChE) and choline acetyltransferase
      (ChAT) activity and positive cells in the hippocampus were detected by the
      biochemical and immunofluorescent assay. Results: All rats were in the same
      baseline. While after model establishment, ability of learning and memory of MG,
      NKG, DBG, NKDBG, and DHG were significantly impaired compared with SOG. Whereas
      after treatment, ability of learning and memory of NKG, DBG, NKDBG, and DHG were
      significantly improved compared with MG. Additionally, AChE activity of NKG, DBG,
      and NKDBG was significantly decreased, meanwhile ChAT activity showed an
      increased tendency. The number of AChE-positive cells and ChAT-positive cells of
      both NKDBG and DHG were significantly decreased and increased respectively,
      superior to those when compared with NKG and DBG. What's more, there was no
      significant difference between NKDBG and DHG. Conclusion: Therapy of dredging the
      bowels could enhance the neuroprotective effect of nourishing kidney herbs by
      reversing morphological damage of hippocampal cholinergic system. Furthermore,
      treatment with NKDB herbs could be effectively against AD, providing a practical
      therapeutic strategy in clinic.

PMID- 30298093
TI  - (+)-Usnic Acid Inhibits Migration of c-KIT Positive Cells in Human Colorectal
      Cancer.
AB  - Inhibition of tumor cell migration is a treatment strategy for patients with
      colorectal cancer (CRC). SCF-dependent activation of c-KIT is responsible for
      migration of c-KIT positive [c-KIT(+)] cells of CRC. Drug resistance to Imatinib
      Mesylate (c-KIT inhibitor) has emerged. Inhibition of mTOR can induce autophagic
      degradation of c-KIT. (+)-usnic acid [(+)-UA], isolated from lichens, has two
      major functions including induction of proton shuttle and targeting inhibition of
      mTOR. To reduce hepatotoxicity, the treatment concentration of (+)-UA should be
      lower than 10 MUM. HCT116 cells and LS174 cells were employed to investigate the
      inhibiting effect of (+)-UA (<10 MUM) on SCF-mediated migration of c-KIT(+) CRC
      cells. HCT116 cells were employed to investigate the molecular mechanisms. The
      results indicated that firstly, 8 MUM (+)-UA decreased ATP content via
      uncoupling; secondly, 8 MUM (+)-UA induced mTOR inhibition, thereby mediated
      activation suppression of PKC-A, and induced the autophagy of the completed
      autophagic flux that resulted in the autophagic degradation and transcriptional
      inhibition of c-KIT and the increase in LDH release; ultimately, 8 MUM (+)-UA
      inhibited SCF-mediated migration of CRC c-KIT(+) cells. Taken together, 8 MUM
      could be determined as the effective concentration for (+)-UA to inhibit SCF
      mediated migration of CRC c-KIT(+) cells.

PMID- 30298094
TI  - Role of Acupuncture in the Management of Severe Acquired Brain Injuries (sABIs).
AB  - Acupuncture therapy has been used to treat several disorders in Asian countries
      and its use is increasing in Western countries as well. Current literature
      assessed the safety and efficacy of acupuncture in the acute management and
      rehabilitation of patients with neurologic disorders. In this paper, the role of
      acupuncture in the treatment of acute severe acquired brain injuries is
      described, acting on neuroinflammation, intracranial oedema, oxidative stress,
      and neuronal regeneration. Moreover, beneficial effects of acupuncture on
      subacute phase and chronic outcomes have been reported in controlling the
      imbalance of IGF-1 hormone and in decreasing spasticity, pain, and the incidence
      of neurovegetative crisis. Moreover, acupuncture may have a positive action on
      the arousal recovery. Further work is needed to understand the effects of
      specific acupoints on the brain. Allegedly concurrent neurophysiological
      measurements (e.g., EEG) may help in studying acupuncture-related changes in
      central nervous system activity and determining its potential as an add-on
      rehabilitative treatment for patients with consciousness disorders.

PMID- 30298095
TI  - Estimating Treatment Effects for Recurrent Events in the Presence of Rescue
      Medications: An Application to the Immune Thrombocytopenia Study.
AB  - In many clinical studies, patients may experience the same type of event of
      interest repeatedly over time. However, the assessment of treatment effects is
      often complicated by the rescue medication uses due to ethical reasons. For
      example, in the motivating trial in studying the Immune Thrombocytopenia (ITP),
      when the interest lies in evaluating the treatment benefit of investigational
      product (IP) on reducing patient's repeated bleeding, rescue medication such as
      platelet transfusions may be allowed to raise platelet counts. Both the intention
      to-treat analysis and treating the intermediate rescue medication as covariate
      tend to attenuate the treatment benefit, and the estimates can be biased if
      interpreted as causal. In this paper, we propose a general causal framework when
      intermediate rescue medications are informative. We adopt the inverse weighted
      estimation approach to estimate the treatment effect, where weights are
      constructed to reflect time-dependent medication use probabilities. The proposed
      estimators are shown to be asymptotically normal and are demonstrated to perform
      well in small-sample simulation studies. The application to the ITP studies
      reveals a stronger benefit of using IP in reducing bleeding.

PMID- 30298096
TI  - The Long-Term Efficacy and Safety of Carotid Artery Stenting among the Elderly: A
      Single-Center Study in China.
AB  - Compared to carotid endarterectomy, carotid artery stenting (CAS) is reportedly
      associated with higher perioperative risks in elderly patients. To verify the
      long-term safety and efficacy of CAS with embolic protection in elderly patients,
      we retrospectively reviewed the medical records of patients with carotid stenosis
      treated between January 2003 and March 2010 at the Department of Neurology of a
      large university hospital in China. We included patients with symptomatic,
      moderate, or severe carotid stenosis of atherosclerotic etiology (other
      etiologies were excluded), with a disability score <= 3 on the modified Rankin
      Scale, and who received CAS instead of carotid endarterectomy. The clinical
      endpoints studied were stroke recurrence and all-cause death. The 84 patients
      included in this study (median follow-up, 8.08 years) were stratified according
      to age at surgery (<70 vs. >=70 years), and no significant between-group
      difference was found regarding baseline characteristics. Of the 14 patients
      (16.67%) who experienced a defined clinical endpoint, 4 (7.14%) were aged <70
      years and 10 (35.71%) were aged >=70 years (P = 0.002). Overall mortality was
      14.29% (12/84), with 3 (5.36%) and 9 (32.14%) deaths among patients aged <70 and
      >= 70 years, respectively (P = 0.002). Heart disease and cancer accounted for
      most deaths. The two groups did not differ regarding stroke recurrence,
      disability score, or rate of in-stent restenosis (blockage >= 50%), but patients
      aged >=70 years had a higher risk of mortality (odds ratio, 8.3684; 95%
      confidence interval, 2.048-34.202; P = 0.003), and age was an independent risk
      factor for death (odds ratio, 20.054; 95% confidence interval, 3.094-129.987, P =
      0.002). Among elderly patients in Southwest China, CAS can effectively prevent
      stroke recurrence without increasing the risk of stroke-related death, but the
      risk of all-cause death is higher, with age as an independent risk factor.
      Careful patient selection is of key importance in the treatment of symptomatic
      carotid artery stenosis.

PMID- 30298097
TI  - Evaluation of A-Site Ba2+-Deficient Ba1-x Co0.4Fe0.4Zr0.1Y0.1O3-delta Oxides as
      Electrocatalysts for Efficient Hydrogen Evolution Reaction.
AB  - Exploring earth-abundant and cost-effective catalysts with high activity and
      stability for a hydrogen evolution reaction (HER) is of great importance to
      practical applications of alkaline water electrolysis. Here, we report on A-site
      Ba2+-deficiency doping as an effective strategy to enhance the electrochemical
      activity of BaCo0.4Fe0.4Zr0.1Y0.1O3-delta for HER, which is related to the
      formation of oxygen vacancies around active Co/Fe ions. By comparison with the
      benchmarking Ba0.5Sr0.5Co0.8Fe0.2O3-delta , one of the most spotlighted
      perovskite oxides, the Ba0.95Co0.4Fe0.4Zr0.1Y0.1O3-delta oxide has lower
      overpotential and smaller Tafel slope. Furthermore, the
      Ba0.95Co0.4Fe0.4Zr0.1Y0.1O3-delta catalyst is ultrastable in an alkaline
      solution. The enhanced HER performance originated from the increased active atoms
      adjacent to oxygen vacancies on the surface of the Ba0.95Co0.4Fe0.4Zr0.1Y0.1O3
      delta catalyst induced by Ba2+-deficiency doping. The low-coordinated active
      atoms and adjacent oxygen ions may play the role of heterojunctions that
      synergistically facilitate the Volmer process and thus render stimulated HER
      catalytic activity. The preliminary results suggest that Ba2+-deficiency doping
      is a feasible method to tailor the physical and electrochemical properties of
      perovskite, and that Ba0.95Co0.4Fe0.4Zr0.1Y0.1O3-delta is a potential catalyst
      for HER.

PMID- 30298098
TI  - MULTI-ENERGY CONE-BEAM CT RECONSTRUCTION WITH A SPATIAL SPECTRAL NONLOCAL MEANS
      ALGORITHM.
AB  - Multi-energy computed tomography (CT) is an emerging medical image modality with
      a number of potential applications in diagnosis and therapy. However, high system
      cost and technical barriers obstruct its step into routine clinical practice. In
      this study, we propose a framework to realize multi-energy cone beam CT (ME-CBCT)
      on the CBCT system that is widely available and has been routinely used for
      radiotherapy image guidance. In our method, a kVp switching technique is
      realized, which acquires x-ray projections with kVp levels cycling through a
      number of values. For this kVp-switching based ME-CBCT acquisition, x-ray
      projections of each energy channel are only a subset of all the acquired
      projections. This leads to an undersampling issue, posing challenges to the
      reconstruction problem. We propose a spatial spectral non-local means (ssNLM)
      method to reconstruct ME-CBCT, which employs image correlations along both
      spatial and spectral directions to suppress noisy and streak artifacts. To
      address the intensity scale difference at different energy channels, a histogram
      matching method is incorporated. Our method is different from conventionally used
      NLM methods in that spectral dimension is included, which helps to effectively
      remove streak artifacts appearing at different directions in images with
      different energy channels. Convergence analysis of our algorithm is provided. A
      comprehensive set of simulation and real experimental studies demonstrate
      feasibility of our ME-CBCT scheme and the capability of achieving superior image
      quality compared to conventional filtered backprojection-type (FBP) and NLM
      reconstruction methods.

PMID- 30298099
TI  - Strategic Improvement for Quality and Satisfaction of Hospital Information
      Systems.
AB  - The purpose of our study aimed to identify attributes capable of improving
      physicians' satisfaction levels with the use of a hospital information system
      (HIS). A model inclusive of system quality, information quality, and service
      quality related to an HIS is used to form antecedents of user satisfaction.
      Survey methodology was used to collect an attributive set representing the system
      quality, information quality, and service quality made available from 150
      physicians at a large health-care system in southern Taiwan. Responses were
      segmented into low and high satisfaction and analyzed with partial least squares
      and importance-performance analysis. The results reveal that system quality,
      information quality, and service quality may be used to significantly predict
      physicians' satisfaction. Two system quality attributes (reliability and response
      time) were identified as the highest priorities for intervention by low- and high
      satisfaction users. Low-satisfaction users further expect improvement of the HIS
      service quality to take place. The subject health-care system should produce
      coping interventions for those high priorities to enhance the satisfaction of
      physicians.

PMID- 30298100
TI  - A Filtering Method for Identification of Significant Target mRNAs of Coexpressed
      and Differentially Expressed MicroRNA Clusters.
AB  - MicroRNA (miRNA) binding is primarily based on sequence, but structure-specific
      binding is also possible. Various prediction algorithms have been developed for
      predicting miRNA target genes; the results, however, have relatively high levels
      of false positives, and the degree of overlap between predicted targets from
      different methods is poor or null. We devised a new method for identifying
      significant miRNA target genes from an extensive list of predicted miRNA target
      gene relationships using hypergeometric distributions. We evaluated our method in
      statistical and semantic aspects using a common miRNA cluster from six solid
      tumors. Our method provides statistically and semantically significant miRNA
      target genes. Complementing target prediction algorithms with our proposed method
      may have a significant synergistic effect in finding and evaluating functional
      annotation and enrichment analysis for miRNA.

PMID- 30298101
TI  - Stroke Outcome and Determinants among Patients with and without Diabetes in a
      Tertiary Hospital in Ghana.
AB  - Background: Diabetes mellitus, a well-established independent risk factor for
      stroke, has varied association with stroke outcome from previous studies. This
      study investigated stroke outcome and determinants among patients with and
      without diabetes in a tertiary hospital in Ghana. Methods: A prospective study
      conducted among stroke patients with and without diabetes admitted in a Ghanaian
      tertiary hospital. Baseline clinical and biochemical data were documented.
      Functional stroke outcome was evaluated at 1, 3, and 6 months after stroke using
      the modified Rankin Scale. Results: Number of participants enrolled were 326 and
      105 (32.20%) had diabetes. Higher proportions of diabetes patients had poor
      functional stroke outcome at 1, 3, and 6 months (79%, 75.23%, 73.33%) compared
      with those without diabetes (70.13%, 65.16, 61.99) (p>0.05). Stroke patients with
      diabetes had lower survival compared with those without diabetes (p=0.0745).
      Mortality at 6 months was more likely among ischaemic stroke patients with
      diabetes compared with those without diabetes (Odds Ratio 2.037; CI: 1.058
      3.923). Determinants of poor functional stroke outcome for diabetes patients were
      older age (Adjusted Odds Ratio (AOR)-1.07; CI-1.03-1.12), female gender (AOR
      3.74; CI-1.26-12.65), and pneumonia (AOR-11.32; CI-1.93-220.05) whereas the
      determinants for those without diabetes were unemployment (AOR-4.19; CI-1.24
      19.50), speech abnormalities (AOR-1.99; CI1.08-3.73), and pneumonia (AOR-4.05; CI
      1.83-9.77). High fasting plasma glucose (HR-1.15; CI-1.07-1.23), elevated
      temperature (HR-1.41; CI-1.11-1.79), and pneumonia (HR-2.25; CI-1.44-3.50) were
      determinants of low survival among all stroke patients. Conclusion: Trends
      towards poorer functional outcome and reduced survival were found among Ghanaian
      stroke patients with diabetes compared with those without diabetes. Older age,
      female gender, pneumonia, elevated temperature, and fasting plasma glucose were
      determinants of adverse outcome in stroke patients with diabetes.

PMID- 30298102
TI  - Synthesis and Characterization of Ionene-Polyamide Materials as Candidates for
      New Gas Separation Membranes.
AB  - A new family of six ionenes containing aromatic amide linkages has been
      synthesized from ready available starting materials at scales up to ~50 g. These
      ionene-polyamides are all constitutional isomers and vary only in the
      regiochemistry of the amide linkages (para, meta) and xylyl linkages (ortho,
      meta, para) which are present in the polymer backbone. This paper details the
      synthesis of these ionenes and associated characterizations. Ionene-polyamides
      exhibit relatively low melting points (~150 oC) allowing them to be readily
      processed into films and other objects. These ionene-polyamide materials are
      being developed for further study as polymer membranes for the separations of
      gases such as CO2, N2, CH4 and H2.

PMID- 30298103
TI  - Assimilation of MODIS Snow Cover Fraction Observations into the NASA Catchment
      Land Surface Model.
AB  - The NASA Catchment land surface model (CLSM) is the land model component used for
      the Modern-Era Retrospective Analysis for Research and Applications (MERRA).
      Here, the CLSM versions of MERRA and MERRA-Land are evaluated using snow cover
      fraction (SCF) observations from the Moderate Resolution Imaging
      Spectroradiometer (MODIS). Moreover, a computationally-efficient empirical scheme
      is designed to improve CLSM estimates of SCF, snow depth, and snow water
      equivalent (SWE) through the assimilation of MODIS SCF observations. Results show
      that data assimilation (DA) improved SCF estimates compared to the open-loop
      model without assimilation (OL), especially in areas with ephemeral snow cover
      and mountainous regions. A comparison of the SCF estimates from DA against snow
      cover estimates from the NOAA Interactive Multisensor Snow and Ice Mapping System
      showed an improvement in the probability of detection of up to 28% and a
      reduction in false alarms by up to 6% (relative to OL). A comparison of the model
      snow depth estimates against Canadian Meteorological Centre analyses showed that
      DA successfully improved the model seasonal bias from -0.017 m for OL to -0.007 m
      for DA, although there was no significant change in root-mean-square differences
      (RMSD) (0.095 m for OL, 0.093 m for DA). The time-average of the spatial
      correlation coefficient also improved from 0.61 for OL to 0.63 for DA. A
      comparison against in situ SWE measurements also showed improvements from
      assimilation. The correlation increased from 0.44 for OL to 0.49 for DA, the bias
      improved from -0.111 m for OL to -0.100 m for DA, and the RMSD decreased from
      0.186 m for OL to 0.180 m for DA.

PMID- 30298104
TI  - Surgical Synechiolysis of Iridocapsular Adhesion and Sulcus Placement of a Rigid
      Intraocular Lens on an Oversized Residual Capsular Rim.
AB  - Purpose: To report the surgical outcomes of surgical synechiolysis of
      iridocapsular adhesion and sulcus placement of a polymethyl methacrylate scleral
      sutured intraocular lens (IOL) in aphakic eyes with an oversized residual
      capsular rim. Methods: Eight aphakic eyes from eight consecutive patients were
      studied retrospectively. Synechiolysis was performed to maximally expose the
      residual capsulorhexis. Then, the rigid IOL was placed on the preserved
      capsulorhexis into the ciliary sulcus. Results: Synechiolysis of iridocapsular
      adhesion was achieved in all eight eyes intraoperatively. Six eyes had extensive
      dissection to facilitate IOL sulcus placement. Consequently, seven of the eight
      eyes had the IOL secured by the residual capsulorhexis, and the other eye had the
      IOL haptics supported by the narrow residual capsular rim. A visual acuity of
      0.25 or above was achieved in four of eight patients, and a well-centered IOL was
      observed in seven of the eight eyes 26 to 53 months after surgery. A mild IOL
      decentration was detected in the eye whose capsular rim was not securing the IOL
      optic. Conclusions: A large-optic and rigid IOL in the sulcus is a feasible
      alternative when a sulcus-based IOL is considered for aphakic eyes with an
      oversized residual capsulorhexis. A preserved capsulorhexis after sufficient
      synechiolysis, which can secure the IOL optic intraoperatively, may yield better
      stability of the IOL position.

PMID- 30298105
TI  - Comparison of the Techniques of Secondary Intraocular Lens Implantation after
      Penetrating Keratoplasty.
AB  - Aim: To conduct a retrospective analysis of secondary IOL implantation in
      patients who underwent PK with no simultaneous IOL implantation. Materials and
      Methods: The retrospective study of the secondary implantation of IOLs was
      conducted in 46 eyes that underwent a primary operation with PK and cataract/lens
      extraction with no IOL implantation due to capsule rupture or combining corneal
      or intraocular complications. The minimum period from PK was 12 months. All
      secondary IOL implantations were performed from January 2011 to August 2017.
      Aphakic postkeratoplasty patients were treated using one of the surgical
      techniques for secondary IOL implantation. In-the-bag IOL implantation was
      possible if the posterior capsule was complete. If the lens capsule remnants were
      sufficient to provide secure IOL support, an in-the-sulcus IOL implantation was
      performed. Scleral fixation was offered in eyes with extensive capsular
      deficiency or the presence of the vitreous body in anterior chamber. BCVA and
      expected and achieved refraction were evaluated; we included using two biometry
      devices, and results were compared. Results: The corrected distance visual acuity
      (CDVA) before surgery ranged from 0.1 to 0.8 (mean 0.54 +/- 0.17). After
      secondary IOL implantation, CDVA ranged from 0.2 to 0.8 (mean 0.43 +/- 0.14) at
      postoperative 1 month and from 0.3 to 0.9 (mean 0.55 +/- 0.15) at postoperative 6
      months (p < 0.05). Comparison of the final refraction using two methods of
      biometry showed no statistically significant difference in the group that
      underwent scleral fixation of the IOL, similar to the findings for the in-the-bag
      and in-the-sulcus IOL implantation groups. In the scleral-fixation group, p=0.55
      for the USG biometry technique and p=0.22 for the OB technique. p values for the
      IOL-implantation group were p=0.49 and p=0.44, respectively. Conclusion: Both
      implantation methods are safe for the patients. Final refraction is depending on
      the technique and indication to keratoplasty. Both biometry techniques deliver
      precise data for IOL choice.

PMID- 30298108
TI  - Early Diagnosis of Nonconvulsive Status Epilepticus Recurrence with Raw EEG of a
      Bispectral Index Monitor.
AB  - Background: Seizures are frequent in ICU and their diagnosis is challenging,
      often delayed or missed. Their diagnosis requires a conventional EEG recording.
      When cEEG is not available, there is no consensus on how patients should be
      monitored when there is high risk of seizure. This case illustrates how a
      bispectral index monitor allowed an early diagnosis of an NCSE recurrence. Case
      Presentation: A NCSE was diagnosed at the admission. cEEG was not available and
      then a bispectral index (BIS) monitor was placed and processed parameters were
      monitored as usual. During the first and second day, both conventional and BIS's
      EEG showed patterns of burst suppression and the BIS value varied between 25 and
      35 while the suppression ratio (SR) varied between 20 and 35. On the third day,
      while hypnotic drugs were withdrawn progressively, raw EEG of the BIS monitor
      showed spikes, spikes waves, and polyspikes without significant variation of BIS
      and SR values. Even if processed parameters stayed between their usual ranges,
      the typical aspect of the real time EEG raised concern for NCSE recurrence. An
      unplanned conventional EEG recording was urgently requested, and the diagnosis
      was confirmed and treated. Conclusion: Primitive and secondary brain injuries can
      lead to seizures which are often purely electrical. Even though BIS monitors
      cannot substitute the conventional EEG, processed parameters and raw EEG should
      be always analysed jointly. In the present case, seizure was suspected only on
      the aspect of real time EEG which showed spikes, spikes waves, and polyspikes.

PMID- 30298107
TI  - Adiposity Is a Key Correlate of Circulating Fibroblast Growth Factor-21 Levels in
      African Males with or without Type 2 Diabetes Mellitus.
AB  - Background: Fibroblast growth factor-21 is an endocrine regulator with
      therapeutic and diagnostic potential. The levels and pattern of circulating FGF
      21 have been described mainly in European and Asian populations. Given its strong
      association with adiposity, and the reported ethnic variabilities in body
      composition, examining FGF-21 in an African population is crucial. Methods: We
      measured levels of circulating FGF-21 in 207 overweight and obese Tanzanian males
      with or without type 2 diabetes mellitus (T2DM), and using statistical
      approaches, we explored their relationship with anthropometric and biochemical
      parameters. Results: Consistent with previous reports from European and Asian
      populations, we found higher levels of FGF-21 in people with T2DM compared to
      those without the disease. Based on statistical models, measures of adiposity
      explained up to 59% of the variability in FGF-21 levels in the circulation.
      Conclusion: Levels of circulating FGF-21 in overweight and obese African males
      are higher in T2DM and strongly correlate with measures of adiposity.

PMID- 30298106
TI  - Knockdown of Fibromodulin Inhibits Proliferation and Migration of RPE Cell via
      the VEGFR2-AKT Pathway.
AB  - Purpose: Recent research has provided novel insight into the function of
      fibromodulin (FMOD) in wound healing and angiogenesis. The role of FMOD in
      initiation of proliferative vitreoretinopathy (PVR) has not been studied. This
      study investigated the effect of FMOD on human retinal pigment epithelial (RPE)
      cell, which plays an essential role in the progression of PVR, and the possible
      mechanisms. Methods: Small interfering (si) RNA-based gene transfer technology
      was used to decrease FMOD expression and to study its effects on RPEs in vitro.
      Cell Counting Kit-8 assays, transwells, and flow cytometry analysis were used to
      measure cell proliferation, migration, cell cycle, and apoptosis. Western blot
      was used to measure expression of vascular endothelial growth factor (VEGF), VEGF
      receptor 2 (VEGFR2), extracellular signal-related kinase 1/2 (ERK1/2), and
      phosphoinositide 3 kinase (PI3K/AKT). Results: After transfection of RPEs with a
      FMOD-specific siRNA, cell proliferation and migration were inhibited to the
      percentage of 65% +/- 5% and 39% +/- 10%, respectively, compared to the control
      group. Depletion of FMOD induced cell cycle arrest and apoptosis in RPE cells.
      Downregulation of VEGF, VEGFR2, and phosphorylated AKT (p-AKT) were detected in
      transfected RPEs. Conclusion: Depletion of FMOD selectively downregulated the
      expression of VEGF and VEGFR2 and inhibited the signaling pathway of AKT
      phosphorylation, which consequently inhibited the proliferation and migration of
      RPE Cell.

PMID- 30298109
TI  - Hemophilia A Complicated by Ulcerative Colitis.
AB  - Background: Hemophilia A is an X-linked recessive disorder characterized by
      defective synthesis of Factor VIII protein. Depending on the level of FVIII
      activity, patients may present with easy bruising, inadequate clotting of
      traumatic or mild injury, or in severe hemophilia, spontaneous hemorrhage.
      Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that is reported
      to have a decreased frequency of occurrence in subjects with coagulation
      disorders. Case: A 26-year-old white male with Hemophilia A was admitted for one
      month of rectal bleeding. The bleeding continued despite Factor VIII replacement
      and colonoscopy and biopsy were performed confirming the presence of active UC.
      Conclusion: Ulcerative colitis with underlying F VIII deficiency can result in
      serious, prolonged, and possibly fatal bleeding if left unrecognized and
      untreated. Treatment of both conditions concurrently utilizing tertiary
      facilities and consultations appears to be the safest strategy for management.

PMID- 30298110
TI  - Elevated CA 125 in a CASE of Leaking Endometrioma.
AB  - Extremely elevated CA 125, usually suggestive of ovarian malignancy, can be found
      in physiological or benign conditions such as endometriosis. We present a case of
      an extremely elevated serum CA 125 level in a patient with stage four
      endometriosis and bilateral unruptured ovarian endometriomas, with evidence of
      leakage unilaterally. To avoid costly and unnecessarily invasive tests and
      procedures it is important to consider the differential diagnosis of
      endometriosis and/or leaking endometrioma in patients with a profoundly elevated
      CA 125 level.

PMID- 30298111
TI  - Changes in Intra-Amniotic, Fetal Intrathoracic, and Intraperitoneal Pressures
      with Uterine Contraction: A Report of Three Cases.
AB  - Intra-amniotic, fetal intrathoracic, and intraperitoneal pressures during
      pregnancy have been previously investigated. However, to our knowledge, changes
      in these pressures during uterine contractions have not been reported. Herein, we
      present three cases of polyhydramnios, fetal pleural effusion, and fetal ascites,
      in which intra-amniotic, fetal intrathoracic, intraperitoneal pressures increased
      with uterine contractions. These pressure increases may affect the fetal
      circulation. We suggest that managing potential premature delivery (e.g., with
      tocolysis) is important in cases with polyhydramnios and excess fluid in fetal
      body areas, such as the thorax, abdomen, and heart. The results of this
      preliminary study on intrafetal pressure measurements will be useful in
      performing fetal and neonatal surgeries in the future.

PMID- 30298112
TI  - Craniofacial Brown Tumor in Patients with Secondary Hyperparathyroidism to
      Chronic Renal Failure: Report of Two Cases in Cipto Mangunkusumo Hospital.
AB  - Brown tumor is a bone lesion that arises in the setting of excess osteoclast
      activity in hyperparathyroidism. It consists of fibrous tissue, woven bone, and
      supporting vasculature, while contains no matrix. The characteristic of brown
      colored lesion is a result of hemosiderin deposition into the osteolytic cysts.
      Two cases of young women aged 26 and 29 years old, respectively, are known with a
      history of end-stage renal disease (ESRD). Dialysis is performed two times/week
      over the last 7 years. Our patients presented with an intraoral mass of the hard
      palate since 12 months ago and decreased body height of 10 cm. The lesion causes
      difficulties in swallowing and talking. Laboratory workup showed elevated
      parathormone or PTH (3.391 pg/mL and >5.000 pg/mL). Neck ultrasound showed
      enlargement of the parathyroid glands. Supporting examination to diagnose brown
      tumor are neck ultrasound, CT of the neck, and parathyroid sestamibi scan. We
      performed parathyroidectomy. Pathology revealed hyperplasia of the parathyroid.
      The tumor regressed significantly within 2 weeks following the surgery, and we
      still observe tumor regression as well as reduction in PTH level. As clinicians,
      we should be alert to other possible causes of bony lesions. Clinical
      examination, laboratory finding, and imaging present important information to
      diagnose brown tumor.

PMID- 30298113
TI  - Management of Small Bowel Perforation by a Bizarre Foreign Body in a 55-Year-Old
      Woman.
AB  - Introduction: Ingestion of foreign bodies including dentures, fishbone, screw,
      and/or surgical devices can be a cause of morbidity, and it rarely could be
      fatal. Presentation of Case: We present the first hitherto reported case of
      mussel shell ingestion, which caused acute abdominal pain in a 55-year-old woman.
      The shell pierced ileal loops, and it was found in the abdominal cavity.
      Discussion: The accidental or voluntary ingestion of a foreign body is an
      uncommon event compared to the other causes of bowel perforation. It is
      fundamental to immediately remove the intestinal fluid, repair the tear, and
      prevent sepsis, because each delay in diagnosis can lead to a worst outcome.
      Conclusion: In case of bowel perforation, it important for surgeons, who are
      dealing with these acute care patients, to be aware of different designs and
      constructions of possible foreign bodies, in order to be prepared to deal with
      different possible scenarios and be able to manage them properly.

PMID- 30298115
TI  - Gas-Phase Synthesis of Nanoparticles: present status and perspectives.
AB  - There is an increasing interest in the generation of well-defined nanoparticles
      (NPs) not only because of their size-related particular properties, but also
      because they are promising building blocks for more complex materials in
      nanotechnology. Here, we will shortly introduce the gas phase synthesis
      technology that has evolved rapidly in the last years and allows the fabrication
      of complex NPs with controllable and tuneable chemical composition and structure
      while keeping very good control over the size distribution. We will also address
      some limitations of the technology (stability over time, production yield...) and
      discuss possible solutions.

PMID- 30298114
TI  - Emergency Laparoscopic Repair of Giant Left Diaphragmatic Hernia following
      Minimally Invasive Esophagectomy: Description of a Case and Review of the
      Literature.
AB  - Postoperative diaphragmatic hernia (PDH) is an increasingly reported complication
      of esophageal cancer surgery. PDH occurs more frequently when minimally invasive
      techniques are employed, but very little is known about its pathogenesis.
      Currently, no consensus exists concerning preventive measures and its management.
      A 71-year-old man underwent minimally invasive esophagectomy for esophageal
      cancer. Three months later, he developed a giant PDH, which was repaired by
      direct suture via laparoscopic approach. A hypertensive pneumothorax occurred
      during surgery. This complication was managed by the anaesthesiologist through a
      high fraction of inspired O2 and several recruitment manoeuvres. The patient
      remained free of hernia recurrence until he died of neoplastic cachexia 5 months
      later. Laparoscopic repair of PDH may be safe and effective even in the acute
      setting and in the case of massive herniation. However, surgeons and
      anaesthesiologists should be aware of the risk of intraoperative pneumothorax and
      be prepared to treat it promptly.

PMID- 30298116
TI  - Analysis of the biodegradation of synthetic testosterone and 17alpha
      ethynylestradiol using the edible mushroom Lentinula edodes.
AB  - The mycelium of Lentinula edodes produces enzymes which may degrade xenobiotics
      including steroid hormones. The aim of the study was to determine whether the
      mycelium from in vitro cultures of L. edodes are able to degrade endocrine
      disruptors such as testosterone and 17alpha-ethynylestradiol. To prove the
      possibility of xenobiotics degradation, cultures of L. edodes were cultivated in
      an Oddoux liquid medium with the addition of synthetic 17alpha-ethynylestradiol
      and synthetic testosterone. The endocrine disruptors were extracted from the
      mycelium and determined qualitatively by RP-HPLC. The degradation products of
      testosterone and 17alpha-ethynylestradiol were identified using a UPLC/MS/MS
      analysis. Undegraded testosterone was determined at the amount of 2.97 mg/g dry
      weight but only in one of the L. edodes extracts from in vitro cultures
      supplemented with 50 mg of this compound. In turn, 17alpha-ethynylestradiol was
      not determined in any samples. Additionally in all extracts, mushroom sterols
      (ergosterol peroxide and ergosterol) were determined. Their total amounts were
      significantly lower in samples containing the abovementioned steroids than in
      extracts from mycelium L. edodes without the addition of steroid hormones. The
      results demonstrated that the mycelium of L. edodes can be used in the
      biodegradation process of a water environment contaminated with endocrine
      disruptors.

PMID- 30298117
TI  - A Single-Chain-Based Hexavalent CD27 Agonist Enhances T Cell Activation and
      Induces Anti-Tumor Immunity.
AB  - Tumor necrosis factor receptor superfamily member 7 (TNFRSF7, CD27), expressed
      primarily by T cells, and its ligand CD27L (TNFSF7, CD70) provide co-stimulatory
      signals that boost T cell activation, differentiation, and survival. Agonistic
      stimulation of CD27 is therefore a promising therapeutic concept in immuno
      oncology intended to boost and sustain T cell driven anti-tumor responses.
      Endogenous TNFSF/TNFRSF-based signal transmission is a structurally well-defined
      event that takes place during cell-to-cell-based contacts. It is well-established
      that the trimeric-trivalent TNFSF-receptor binding domain (TNFSF-RBD) exposed by
      the conducting cell and the resulting multi-trimer-based receptor clustering on
      the receiving cell are essential for agonistic signaling. Therefore, we have
      developed HERA-CD27L, a novel hexavalent TNF receptor agonist (HERA) targeting
      CD27 and mimicking the natural signaling concept. HERA-CD27L is composed of a
      trivalent but single-chain CD27L-receptor-binding-domain (scCD27L-RBD) fused to
      an IgG1 derived silenced Fc-domain serving as dimerization scaffold. The
      hexavalent agonist significantly boosted antigen-specific T cell responses while
      having no effect on non-specific T cells and was superior over stabilized
      recombinant trivalent CD27L. In addition, HERA-CD27L demonstrated potent single
      agent anti-tumor efficacy in two different syngeneic tumor models, MC38-CEA and
      CT26wt. Furthermore, the combination of HERA-CD27L and an anti-PD-1 antibody
      showed additive anti-tumor effects highlighting the importance of both T cell
      activation and checkpoint inhibition in anti-tumor immunity. In this manuscript,
      we describe the development of HERA-CD27L, a true CD27 agonist with a clearly
      defined forward-signaling mechanism of action.

PMID- 30298119
TI  - Preclinical Evaluation of White Led-Activated Non-porphyrinic Photosensitizer
      OR141 in 3D Tumor Spheroids and Mouse Skin Lesions.
AB  - Photodynamic therapy (PDT) is used to treat malignancies and precancerous
      lesions. Near-infrared light delivered by lasers was thought for a while to be
      the most appropriate option to activate photosensitizers, mostly porphyrins, in
      the depth of the diseased tissues. More recently, however, several advantages
      including low cost and reduced adverse effects led to consider light emitting
      diodes (LED) and even daylight as an alternative to use PDT to treat accessible
      lesions. In this study we examined the capacity of OR141, a recently identified
      non-porphyrin photosensitizer (PS), to exert significant cytotoxic effects in
      various models of skin lesions and tumors upon white light activation. Using
      different cancer cell lines, we first identified LED lamp as a particularly
      suited source of light to maximize anti-proliferative effects of OR141. We then
      documented that OR141 diffusion and light penetration into tumor spheroids both
      reached thresholds compatible with the induction of cell death deep inside these
      3D culture models. We further identified Arlasove as a clinically suitable
      solvent for OR141 that we documented by using Franz cells to support significant
      absorption of the PS through human skin. Finally, using topical but also systemic
      administration, we validated growth inhibitory effects of LED-activated OR141 in
      mouse skin tumor xenograft and precancerous lesions models. Altogether these
      results open clinical perspectives for the use of OR141 as an attractive PS to
      treat superficial skin malignant and non-malignant lesions using affordable LED
      lamp for photoactivation.

PMID- 30298118
TI  - New Frontiers for the Cytoskeletal Protein LASP1.
AB  - In the recent two decades, LIM and SH3 protein 1 (LASP1) has been developed from
      a simple actin-binding structural protein to a tumor biomarker and subsequently
      to a complex, nuclear transcriptional regulator. Starting with a brief historical
      perspective, this review will mainly compare and contrast LASP1 and LASP2 from
      the angle of the newest data and importantly, examine their role in
      transcriptional regulation. We will summarize the current knowledge through
      pictorial models and tables including the roles of different microRNAs in the
      differential regulation of LASP1 levels and patient outcome rather than specify
      in detail all tumor entities. Finally, the novel functional roles of LASP1 in
      secretion of vesicles, expression of matrix metalloproteinases and
      transcriptional regulation as well as the activation of survival and
      proliferation pathways in different cancer types are described.

PMID- 30298120
TI  - Mevalonate Metabolism in Cancer Stemness and Trained Immunity.
AB  - Mevalonate metabolism provides cancer and immune cells with diverse products to
      ensure cell functionality. Similar metabolic reprogramming that raises mevalonate
      metabolism to higher levels appears to drive both, epithelial mesenchymal
      transition (EMT) of cancer cells, a reverse differentiation program that
      generates cancer cells with stem cell properties, and immune cell training for
      increased responsiveness to secondary stimulation. In this review, we address how
      mevalonate metabolism supports cancer development and stemness on the one hand,
      and on the other promotes immune responsiveness. In view of this dual nature of
      mevalonate metabolism, strategies to manipulate this metabolic pathway as part of
      anti-cancer therapies require careful analysis of risks versus benefits.

PMID- 30298122
TI  - Prevalence of Yersinia Species in the Ileum of Crohn's Disease Patients and
      Controls.
AB  - Yersinia are common contaminants of food products, but their prevalence in the
      human gut is poorly documented. Yersinia have been implicated in Crohn's Disease
      (CD, an inflammatory bowel disease) however their role in CD is controversial. We
      performed highly sensitive PCR assays of specific sequences for the gyrB gene of
      Y. aldovae, Y. bercovieri, Y. enterocolitica, Y. intermedia, Y. mollaretii and
      the inv gene of Y. pseudotuberculosis. We analyzed a total of 470 ileal samples
      taken from 338 participants (262 CD patients and 76 controls) belonging to three
      independent cohorts. All patients and controls were phenotyped and genotyped for
      the main CD susceptibility variants: NOD2, ATG16L1, and IRGM. Yersinia were found
      in 7.7% of ileal samples (respectively 7.9 and 7.6% in controls and CD patients)
      corresponding to 10% of participants (respectively 11.8 and 9.5% in controls and
      CD patients). Y. enterocolitica, Y. pseudotuberculosis and Y. intermedia were the
      most frequently identified species. The bacteria were more frequent in resected
      specimens, lymph nodes and Peyer's patches. Yersinia were no more likely to be
      detected in CD tissues than tissues from inflammatory and non-inflammatory
      controls. CD patients treated with immunosuppressants were less likely to be
      Yersinia carriers. In conclusion, this work shows that Yersinia species are
      frequently found at low levels in the human ileum in health and disease. The role
      of Yersinia species in this ecosystem should now be explored.

PMID- 30298121
TI  - Translational Potential of Therapeutics Targeting Regulatory Myeloid Cells in
      Tuberculosis.
AB  - Despite recent advances in tuberculosis (TB) drug development and availability,
      successful antibiotic treatment is challenged by the parallel development of
      antimicrobial resistance. As a result, new approaches toward improving TB
      treatment have been proposed in an attempt to reduce the high TB morbidity and
      mortality rates. Host-directed therapies (HDTs), designed to modulate host immune
      components, provide an alternative approach for improving treatment outcome in
      both non-communicable and infectious diseases. Many candidate immunotherapeutics,
      designed to target regulatory myeloid immune components in cancer, have so far
      proven to be of value as repurposed HDT in TB. Several of these studies do
      however lack detailed description of the mechanism or host pathway affected by TB
      HDT treatment. In this review, we present an argument for greater appreciation of
      the role of regulatory myeloid cells, such as myeloid-derived suppressor cells
      (MDSC), as potential targets for the development of candidate TB HDT compounds.
      We discuss the role of MDSC in the context of Mycobacterium tuberculosis
      infection and disease, focussing primarily on their specific cellular functions
      and highlight the impact of HDTs on MDSC frequency and function.

PMID- 30298123
TI  - Osteogenic Sarcoma in an Adolescent With Cystic Fibrosis: Successful Treatment
      Despite Significant Obstacles.
AB  - Introduction: We describe the case of a 16-year old male with cystic fiborosis
      (CF) who presented with an osteosarcoma of his right distal tibia. Case Report:
      Treatment consisted of neoadjuvant chemotherapy of cisplatin, doxorubicin and
      high dose methotrexate followed by distal tibial resection and free fibula flap
      reconstruction and consolidation chemotherapy. Treatment was complicated by a
      pulmonary exacerbation, where Pseudomonas aeruginosa (PsA) and Staphylococcus
      aureus were grown on sputum culture which was treated with a 2-week course of
      intravenous piptazobactam and tobramycin. Mycobacterium intracellulare and
      Mycobacterium abscessus were also cultured following commencement of chemotherapy
      and successfully treated with a 6-month course of oral azithromycin, ethambutol,
      and moxifloxacin along with a 1-month course of inhaled amikacin. Pulmonary
      function improved during his treatment from baseline FEV1 of 3.8 l (93.9%) to
      4.15 l (102.3% predicted) whilst nutritional status remained stable. Discussion:
      The combination of CF and osteosarcoma is rare with only one previous case
      reported (1). Our case is instructive as the patient faced the challenge of
      chronic PsA and the first reported culturing and successful treatment of non
      tuberculous mycobacterium (NTM) during chemotherapy. Fatal outcomes have been
      reported previously for CF patients during immunosuppression (2). In concordance
      with our findings, a recent report noted an improvement in respiratory function
      in a child treated for leukemia (3). The anti-inflammatory nature of some
      chemotherapy agents could be responsible for the observed clinical improvement in
      CF with low dose methotrexate having been shown to increase FEV1 in adolescents
      with advanced CF (4). Whilst doxorubicin could improve pulmonary outcomes through
      increased total cellular CFTR protein expression and CFTR associated chloride
      secretion (5). It is hypothesized that the improved pulmonary function in
      patients with CF who require chemotherapy could be due to increased production of
      Multi-Drug Resistance Proteins (MDR) and Multi-Drug Resistant Associated Proteins
      (MRP) that may complement the depleted CFTR protein (6). Concluding Remarks: We
      report the well-tolerated management of osteosarcoma in a patient with CF
      including the first reported identification and eradication of NTM during
      chemotherapy. The observed positive pulmonary outcome following chemotherapy
      highlights several potential cellular mechanisms that deserve to be explored.

PMID- 30298124
TI  - Classification of Pediatric Asthma: From Phenotype Discovery to Clinical
      Practice.
AB  - Advances in big data analytics have created an opportunity for a step change in
      unraveling mechanisms underlying the development of complex diseases such as
      asthma, providing valuable insights that drive better diagnostic decision-making
      in clinical practice, and opening up paths to individualized treatment plans.
      However, translating findings from data-driven analyses into meaningful insights
      and actionable solutions requires approaches and tools which move beyond mining
      and patterning longitudinal data. The purpose of this review is to summarize
      recent advances in phenotyping of asthma, to discuss key hurdles currently
      hampering the translation of phenotypic variation into mechanistic insights and
      clinical setting, and to suggest potential solutions that may address these
      limitations and accelerate moving discoveries into practice. In order to advance
      the field of phenotypic discovery, greater focus should be placed on
      investigating the extent of within-phenotype variation. We advocate a more
      cautious modeling approach by "supervising" the findings to delineate more
      precisely the characteristics of the individual trajectories assigned to each
      phenotype. Furthermore, it is important to employ different methods within a
      study to compare the stability of derived phenotypes, and to assess the
      immutability of individual assignments to phenotypes. If we are to make a step
      change toward precision (stratified or personalized) medicine and capitalize on
      the available big data assets, we have to develop genuine cross-disciplinary
      collaborations, wherein data scientists who turn data into information using
      algorithms and machine learning, team up with medical professionals who provide
      deep insights on specific subjects from a clinical perspective.

PMID- 30298125
TI  - Probing the Origins of 1,800 MHz Radio Frequency Electromagnetic Radiation
      Induced Damage in Mouse Immortalized Germ Cells and Spermatozoa in vitro.
AB  - As the use of mobile phone devices is now highly prevalent, many studies have
      sought to evaluate the effects of the radiofrequency-electromagnetic radiation
      (RF-EMR) on both human health and biology. While several such studies have shown
      RF-EMR is capable of inducing cellular stress, the physicobiological origin of
      this stress remains largely unresolved. To explore the effect of RF-EMR on the
      male reproductive system, we exposed cultured mouse spermatogonial GC1 and
      spermatocyte GC2 cell lines, as well as cauda epididymal spermatozoa to a
      waveguide generating continuous wave RF-EMR (1.8 GHz, 0.15 and 1.5 W/kg). This
      study demonstrated that a 4 h exposure is capable of inducing the generation of
      mitochondrial reactive oxygen species (ROS) in populations of GC1 (7 vs. 18%; p <
      0.001) and GC2 cells (11.5 vs. 16 %; p < 0.01), identifying Complex III of the
      electron transport chain (ETC) as the potential source of electrons producing
      ROS. Assessing the generation of ROS in the presence of an antioxidant,
      penicillamine, as well as measuring lipid peroxidation via 4-hydroxynonenal
      levels, indicated that the elevated incidence of ROS generation observed under
      our exposure conditions did not necessarily induce an overt cellular oxidative
      stress response. However, exposure to RF-EMR at 0.15 W/kg for 3 h did induce
      significant DNA fragmentation in spermatozoa (that was no longer significant
      after 4 h), assessed by the alkaline comet assay (p < 0.05). Furthermore, this
      fragmentation was accompanied by an induction of oxidative DNA damage in the form
      of 8-hydroxy-2'-deoxyguanosine, which was significant (p < 0.05) after
      spermatozoa were exposed to RF-EMR for 4 h. At this exposure time point, a
      decline in sperm motility (p < 0.05) was also observed. This study contributes
      new evidence toward elucidating a mechanism to account for the effects of RF-EMR
      on biological systems, proposing Complex III of the mitochondrial ETC as the key
      target of this radiation.

PMID- 30298126
TI  - Successful Curriculum Change in Health Management and Leadership Studies for the
      Specialist Training Programs in Medicine in Finland.
AB  - In Finland, the specialization programs in Medicine and Dentistry can be
      undertaken at all five university medical faculties in 50 specialization programs
      and in five programs for Dentistry. The specialist training requires 5 or 6 years
      (300-360 ECTS credits) of medical practice including 9 months of service in
      primary health care centers, theoretical substance specific education, management
      studies, and passing a national written exam. The renovation of the national
      curriculum for the specialization programs was implemented, first in 2008 and
      officially in August 2009, when theoretical multi-professional social, health
      management and leadership studies (10-30 ECTS credits) were added to the
      curriculum. According to European Credit Transfer and Accumulation System (ECTS),
      1 ECTS credit (henceforth, simply "ECTS") means 27-30 h of academic work National
      guidelines for the multi-professional leadership training include the basics of
      organizational management and leadership, the social and healthcare system, human
      resources (HR) management, leadership interaction and organizational
      communication, healthcare economy, legislation (HR) and data management. Each
      medical faculty has implemented management studies autonomously but according to
      national guidelines. This paper will describe how the compulsory management
      studies (10 ECTS) have been executed at the Universities of Tampere and Turku. In
      Tampere, the 10 ECTS management studies follow a flexible design of six academic
      modules. Versatile modern teaching methods such as technology-assisted and
      student orientated learning are used. Advanced supplementary management studies
      (20 ECTS) are also available. In Turku, the 10 ECTS studies consist of academic
      lectures, portfolio and project work. Attendees select contact studies (4-6 ECTS)
      from yearly available 20 ECTS and proceed at their own pace. Portfolio and
      project comprise 2-5 ECTS each. The renovation of medical specializing
      physicians' management and leadership education has been a successful reform. It
      has been observed that positive attitudes and interest toward management overall
      are increasing among younger doctors. In addition, management and leadership
      education will presumably facilitate medical doctors' work as managers also.
      Continuous development of medical doctors' management and leadership education
      for physicians and dentists is needed while the changing and complex healthcare
      environment requires both professional and leadership expertise.

PMID- 30298127
TI  - Protected and De-protected Platinum(IV) Glycoconjugates With GLUT1 and OCT2
      Mediated Selective Cancer Targeting: Demonstrated Enhanced Transporter-Mediated
      Cytotoxic Properties in vitro and in vivo.
AB  - Physiological characteristics of human malignancies are increased glycolysis and
      overexpression of glucose transporters (GLUTs). 18Flurodeoxyglucose-positron
      emission tomography (FDG-PET) has successfully developed as clinical modality for
      the diagnosis and staging of many cancers based on the Warburg effect. To
      leverage this glucose transporter mediated metabolic disparity between normal and
      malignant cells, in the current report, protected, and de-protected glucose,
      mannose, galactose, rhamnose, maltose, and lactose-conjugated platinum(IV)
      complexes were designed and synthesized. The suggested potential of facilitated
      intravenous to oral switching of glycosylated platinum(IV) prodrugs with cancer
      targeting properties were evaluated for glucose transporter 1 (GLUT1) and organic
      cation transporter 2 (OCT2)-mediated selective properties in vitro and in vivo.
      The cytotoxicity of 2d, 5d, and 6d were ~23-fold greater than that of the
      positive controls cisplatin, oxaliplatin, and satraplatin, respectively. The
      leading compound 6d, the IC50 of which with the GLUT1 inhibitor 4,6-oethylidene
      alpha-D-glucose (EDG) and phloretin (31.80 and 38.71 MUM) are 36- and 44-folds
      higher, respectively, than the 48 h IC50 (0.89 MUM), is superior to the reported
      5-8, exhibiting enhanced cancer targeting. The compounds also showed reduced
      toxicity to normal cells (293T IC50 = 12.06 MUM and 3T3 cells IC50 > 100 MUM) and
      exhibited no cross-resistance to cisplatin. Moreover, the encouraging selectivity
      of 6d for MCF-7 cells in vivo indicated that the pyranoside performs an important
      function in cancer targeting.

PMID- 30298128
TI  - Electrocatalysis of Lindane Using Antimony Oxide Nanoparticles Based-SWCNT/PANI
      Nanocomposites.
AB  - This work describes the chemical synthesis of antimony oxide nanoparticles
      (AONPs), polyaniline (PANI), acid functionalized single-walled carbon nanotubes
      (fSWCNTs), and the nanocomposite (AONP-PANI-SWCNT) as catalyst for the trace
      detection of lindane. Successful synthesis of the nanomaterials was confirmed by
      Fourier transform infrared (FT-IR) spectroscopy, ultraviolet-visible (UV-Vis)
      spectroscopy, x-ray diffraction (XRD) spectroscopy, and scanning electron
      microscopy (SEM). Cyclic voltammetry (CV) and electrochemical impedance
      spectroscopy (EIS) were used for investigating the electrochemical behavior of
      the modified electrodes in the ferrocyanide/ferricyanide ([Fe(CN)6]4-/[Fe(CN)6]3
      ) redox probe. GCE-AONP-PANI-SWCNT exhibited faster electron transport properties
      as well as higher electroactivity as compared to bare-GCE, GCE-AONPs, GCE-PANI,
      and GCE-SWCNT electrodes. Electrocatalytic studies further showed that GCE-AONP
      PANI-SWCNT modified electrode was stable (after 20 scans) with only a small
      current drop in lindane (0.57%). The GCE-AONP-PANI-SWCNT electrode with low
      detection limit of 2.01 nM performed better toward the detection of lindane as
      compared to other studies in literature. The GCE-AONP-PANI-SWCNT electrode is
      highly selective toward the detection of lindane in the presence of various
      organic and inorganic interfering species. Real sample analysis of river water
      and tap water samples using the developed sensor gave satisfactory percentage
      recoveries therefore confirming the potential of the proposed sensor for
      practical application.

PMID- 30298129
TI  - Recent Progress in European Advanced Therapy Medicinal Products and Beyond.
AB  - Cell- and gene-based therapies form one of the pillars of regenerative medicine.
      They have the potential to transform quality of life and improve the health
      status of patients with genetic and cellular defects, including genetic diseases,
      neurodegenerative diseases and tissue malignancies, amongst others. Despite
      numerous challenges, in the last decade, tremendous unified efforts by research
      and clinical scientists in academic, translational and industry settings have
      resulted in tangible outcomes in the form of many marketing authorizations and
      approved commercial firsts, such as Glybera(r), Kymriah(r), YESCARTA(r),
      Holoclar(r), and LuxturnaTM. This report presents a succinct analysis of
      developments in the regenerative medicine landscape, including immuno-oncology,
      with a focus on the European Union and examples of clinical and commercial
      successes and failures. The factors that led to these exciting developments in
      immune-oncology are also considered. Concurrently, several key issues, spanning
      from the identification of unmet clinical need, associated challenges, economic
      evaluation to policy improvements are emphasized. Furthermore, industry insights
      encompassing the five-dimensional research and development framework for the
      focused development of medicine, pricing and reimbursement issues, technology
      adoption and permeation of innovative advanced therapy medicinal products in the
      clinical set up are reflected upon, following elaborate discussions that
      transpired in different thematic tracks of Tissue Engineering & Regenerative
      Medicine International Society European Chapter 2017 Industry Symposium.

PMID- 30298132
TI  - "Real-Time" High-Throughput Drug and Synergy Testing for Multidrug-Resistant
      Bacterial Infection: A Case Report.
AB  - Antibiotic management of infections with multidrug-resistant organisms (MDRO)
      represents a complex clinical challenge. We report here the first patient with a
      severe MDRO infection managed with assistance of a novel "real-time" 3-day high
      throughput screen (HTS) that allowed screening of 9 drugs in 14 combinations in
      2,304 total samplings. Identified synergies were used to modify patient therapy
      with the goal of reducing drug-induced toxicity. The desired clinical outcome was
      achieved on the HTS-informed therapeutic regimen, supporting the utility of HTS
      technology to expand standard antimicrobial susceptibility testing.

PMID- 30298131
TI  - A Fatal Bacteremia Caused by Hypermucousviscous KPC-2 Producing Extensively Drug
      Resistant K64-ST11 Klebsiella pneumoniae in Brazil.
AB  - We report a fatal bacteremia caused by Klebsiella pneumoniae in a 60-70-year-old
      patient from Brazil. The genomic analysis of three isolates (from blood culture,
      nasal and anal swabs) showed that the bacteremia was caused by a KPC-2 producing
      extensively drug-resistant K64-ST11 hypermucousviscous K. pneumoniae (hmKP)
      harboring several virulence and antimicrobial resistance genes. Although the
      isolates did not present virulence markers associated with hypervirulent K.
      pneumoniae (hvKP), they showed invasion and toxicity to epithelial Hep-2 cells;
      resistance to cell microbicidal mechanisms; and blood and human serum survival,
      evidencing their pathogenic potential. This study highlights the risk of
      infection caused by hmKp strains not characterized as hvKP as well as the
      clinical implications and difficulty of treatment, especially in elderly or
      immunocompromised patients.

PMID- 30298134
TI  - Effect of Floor Cooling on Behavior and Heart Rate of Late Lactation Sows Under
      Acute Heat Stress.
AB  - Much U.S. swine production is in Koppen climate types classified as "hot-summer
      humid continental" and "humid subtropical." As a result, farrowing sows are often
      exposed to temperatures above their upper critical temperature. This heat stress
      (HS) can affect sow welfare and productivity and have a negative economic impact.
      The study objective was to evaluate the impact of a cooling pad on sows'
      behavioral and heart rate responses to acute HS. Treatments were randomly
      allotted to ten multiparous sows to receive a constant cool water flow of 0.00
      (CONTROL, n = 4), 0.25 (LOW, n = 2), 0.55 (MEDIUM, n = 2), or 0.85 (HIGH, n = 2)
      L/min for 100 min and replicated eight times, switching treatments so that each
      sow was exposed to each treatment. The cooling was initiated 1 h after the room
      reached 35 degrees C for 100 min. Eating, drinking and nursing behaviors,
      postures, and heart rate were recorded before heating (Period 1), prior to
      cooling (Period 2), and during cooling (Period 3). There were no differences
      between LOW, MEDIUM, and HIGH flow rates for any periods on all behavioral and
      heart rate traits, so data were pooled (COOLED). There were no differences in any
      of the measures during Periods 1 and 2, except for the ratio of short term to
      long term heart rate variability (SD1:SD2) with higher values for CONTROL than
      COOLED sows in Period 2. During Period 3, CONTROL sows changed postures more
      frequently (11.5 +/-1.6 vs. 5.1 +/-1.6 changes per hour), spent more time drinker
      pressing/drinking (4.4 +/- 0.5 vs. 1.4 +/- 0.4% of time), standing (6.6 +/- 1.7
      vs. 3.8 +/- 1.6% of time), sitting (10.0 +/- 1.2 vs. 4.0 +/- 1.1), less time
      lying (83.0 +/-1.8 vs. 92.0 +/-1.7% of time), especially lying laterally (62.0 +/
      5.6 vs. 75.0 +/- 5.3% of time), than sows in all three cooling treatments (all P
      < 0.001). Heart rate during Period 3 was lower for COOLED sows compared to the
      CONTROL sows (100.2 +/- 3.4 vs. 119.0 +/- 4.0 beat per min, P < 0.001). Sows
      response to increased thermal load can be effectively reduced using water-cooled
      cooling pads, thereby improving sow comfort and welfare. The beneficial effects
      on behavior are noticeable from the lowest flow rate.

PMID- 30298130
TI  - Pathophysiology of Trans-Synaptic Adhesion Molecules: Implications for Epilepsy.
AB  - Chemical synapses are specialized interfaces between neurons in the brain that
      transmit and modulate information, thereby integrating cells into multiplicity of
      interacting neural circuits. Cell adhesion molecules (CAMs) might form trans
      synaptic complexes that are crucial for the appropriate identification of
      synaptic partners and further for the establishment, properties, and dynamics of
      synapses. When affected, trans-synaptic adhesion mechanisms play a role in
      synaptopathies in a variety of neuropsychiatric disorders including epilepsy.
      This review recapitulates current understanding of trans-synaptic interactions in
      pathophysiology of interneuronal connections. In particular, we discuss here the
      possible implications of trans-synaptic adhesion dysfunction for epilepsy.

PMID- 30298133
TI  - The Role of Polyphenols in Human Health and Food Systems: A Mini-Review.
AB  - This narrative mini- review summarizes current knowledge of the role of
      polyphenols in health outcomes-and non-communicable diseases specifically-and
      discusses the implications of this evidence for public health, and for future
      directions for public health practice, policy, and research. The publications
      cited originate mainly from animal models and feeding experiments, as well as
      human cohort and case-control studies. Hypothesized protective effects of
      polyphenols in acute and chronic diseases, including obesity, neurodegenerative
      diseases, type 2 diabetes, and cardiovascular diseases, are evaluated. Potential
      harmful effects of some polyphenols are also considered, counterbalanced with the
      limited evidence of harm in the research literature. Recent international
      governmental regulations are discussed, as the safety and health claims of only a
      few specific polyphenolic compounds have been officially sanctioned. The
      implications of food processing on the bioavailability of polyphenols are also
      assessed, in addition to the health claims and marketing of polyphenols as a
      functional food. Finally, this mini-review asserts the need for increased
      regulation and guidelines for polyphenol consumption and supplementation in order
      to ensure consumers remain safe and informed about polyphenols.

PMID- 30298135
TI  - Microbubble-Mediated Ultrasound Outweighs Low-Intensity Pulsed Ultrasound on
      Osteogenesis and Neovascularization in a Rabbit Model of Steroid-Associated
      Osteonecrosis.
AB  - Microbubbles magnify the acoustic pressure of low-intensity pulsed ultrasound
      (LIPUS) and may enhance its bioeffect for diagnostic and therapeutic purposes.
      This study compared the effect of this novel microbubble-mediated ultrasound
      (MUS) with that of the traditional LIPUS on osteogenesis and neovascularization
      in a rabbit model of steroid-associated osteonecrosis. We hypothesized that MUS
      might outweigh LIPUS on promoting osteogenesis and neovascularization in steroid
      associated osteonecrosis. The bilateral femoral head necrosis was induced by
      lipopolysaccharide and methylprednisolone in the rabbits. The indices of bone
      mineral density (BMD), trabecular number, maximal loading strength, and mineral
      apposition rate were analyzed, demonstrating that the animal model of steroid
      associated osteonecrosis was successfully established. Both the MUS group (GM)
      and the LIPUS group (GL) were insonated 20 min daily for six weeks. GM received
      an extra intracapsular injection of microbubbles before insonation every other
      day. Fluorescence bone labeling, Micro-CT Analysis, biomechanical test,
      quantitative real-time PCR, Western blot analysis, and histological evaluation
      were performed for comparing GM with GL. The results demonstrated a 39% higher
      mineral apposition rate in GM compared with GL. The BMD and the maximal loading
      strength of femoral head of GM increased by 4.3% and 27.8% compared to those of
      GL, respectively. The mRNA and protein expression of BMP-2 and VEGF were also
      significantly higher in GM. The number of blood vessels of GM was 65% greater
      than that of GL. MUS is more potent than LIPUS in enhancing osteogenesis,
      neovascularization, and biomechanical strength of femoral head in the animal
      model of steroid-associated osteonecrosis. Without increasing the intensity of
      insonation or the risk of tissue damage, MUS is better for inhibiting the process
      of steroid-associated osteonecrosis.

PMID- 30298136
TI  - The Antimicrobial Peptide Nal-P-113 Exerts a Reparative Effect by Promoting Cell
      Proliferation, Migration, and Cell Cycle Progression.
AB  - Objective: The primary purpose of this study was to evaluate the reparative
      efficacy of a novel antimicrobial peptide, Nal-P-113, in shortening the healing
      time of oral mucosal ulcers by promoting cell proliferation and migration and
      accelerating the cell cycle. Methods: Cell counting kit-8 (CCK-8) and wound
      healing assays were used to evaluate the proliferation and migration of human
      immortalized oral epithelial cells (HIOECs). The cell cycle distribution of
      HIOECs was analyzed by flow cytometry. Additionally, the RNA levels of EGF, FGF
      2, and TGF-beta1 of HIOECs were assessed by real-time PCR. Rats were divided into
      three groups randomly: (a) blank control group; (b) 20 MUg/mL Nal-P-113; and (c)
      10 ng/mL rhEGF. An oral mucosal ulcer was induced in every rat by the application
      of 30% acetic acid. An immunohistochemical assay was used to assess the
      expression of EGF, FGF-2, and TGF-beta1 in the rat oral mucosa. Results: In the
      CCK-8 assay, the optical density values in the Nal-P-113 and rhEGF groups were
      found to be significantly higher than that in the blank control group. In
      addition, the scratch areas in the Nal-P-113 and rhEGF groups were found to be
      significantly smaller (P<0.05). Cell cycle analysis showed that Nal-P-113
      accelerated the entry of HIOECs into the S phase and expedited their cell cycles.
      The RT-PCR results suggested that Nal-P-113 upregulated the RNA levels of EGF and
      FGF-2 but downregulated that of TGF-beta1 at 24 h and 48 h. Lastly, the
      immunohistochemical assay verified that Nal-P-113 changed the expression of the
      above cytokines in rat mucosal ulcers. Conclusion: Nal-P-113 promoted the repair
      of oral mucosal ulcers by increasing the EGF and FGF-2 expression and decreasing
      that of TGF-beta1 in HIOECs, accelerating their proliferation and cell cycle
      progression. The application of Nal-P-113 might serve as an effective therapeutic
      approach for recurrent aphthous stomatitis.

PMID- 30298137
TI  - Identification of Genetic Risk Factors for Neonatal Hyperbilirubinemia in Fujian
      Province, Southeastern China: A Case-Control Study.
AB  - To date, the genetic risk factors for neonatal hyperbilirubinemia remain unknown
      in Southeastern China. This case-control study aimed to identify the genetic risk
      factors for neonatal hyperbilirubinemia in Fujian, Southeastern China. A total of
      286 hyperbilirubinemic newborns were enrolled as a case group, and 250 randomly
      selected newborns without jaundice or with a bilirubin level that was lower than
      the threshold required for phototherapy served as controls. The serum levels of
      total bilirubin, unconjugated bilirubin, and direct bilirubin were measured, and
      the common genetic loci in UGT1A1, OATP1B1, and HO-1 genes were genotyped. Higher
      incidence of ABO incompatibility and G6PD deficiency was detected in the case
      group compared to the control group (P < 0.01). There were significant
      differences in the frequencies of rs4148323 and rs1805173 genotypes between the
      case and control groups (P < 0.05). At the rs4148323 locus, the frequencies of GA
      heterozygotes and AA mutant homozygotes were higher in the case group than in the
      control group (P < 0.05), and at the rs1805173 locus, the frequencies of LS, MS,
      and SS genotypes were higher in the case group than in the control group (P <
      0.05). A higher frequency of rs4148323 A allele and rs1805173 S allele was
      detected in the case group compared to the control group (P = 0). Additionally,
      multivariate logistic regression analysis identified that the mutant genotype of
      rs4148323 in the UGT1A1 gene, ABO incompatibility, G6PD deficiency, and SS
      genotype at rs1805173 locus of the HO-1 gene were genetic risk factors of
      neonatal hyperbilirubinemia. Our data demonstrate that G211 mutation in the
      UGT1A1 gene, ABO incompatibility, G6PD deficiency, and the SS genotype of the
      repeats in the promoter region of the HO-1 gene are risk factors for neonatal
      hyperbilirubinemia in Fujian, Southeastern China.

PMID- 30298138
TI  - Inflammatory-Driven Angiogenesis in Bone Augmentation with Bovine Hydroxyapatite,
      B-Tricalcium Phosphate, and Bioglasses: A Comparative Study.
AB  - Introduction: The clinical use of bioactive materials for bone augmentation has
      remained a challenge because of predictability and effectiveness concerns, as
      well as increased costs. The purpose of this study was to analyse the ability to
      integrate bone substitutes by evaluating the immunohistochemical expression of
      the platelet endothelial cell adhesion molecules, vascular endothelial growth
      factor, collagen IV, laminin, and osteonectin, in the vicinity of bone grafts,
      enabling tissue revascularization and appearance of bone lamellae. There is a
      lack of in vivo studies of inflammatory-driven angiogenesis in bone engineering
      using various grafts. Methods: The study was performed in animal experimental
      model on the standardized monocortical defects in the tibia of 20 New Zealand
      rabbits. The defects were augmented with three types of bone substituents. The
      used bone substituents were beta-tricalcium phosphate, bovine hydroxyapatite, and
      bioactive glasses. After a period of 6 months, bone fragments were harvested for
      histopathologic examination. Endothelial cell analysis was done by analysing
      vascularization with PECAM/CD31 and VEGF and fibrosis with collagen IV, laminin,
      and osteonectin stains. Statistical analysis was realized by descriptive analysis
      which was completed with the kurtosis and skewness as well as the Kruskal-Wallis
      and Mann-Whitney statistical tests. Results: The discoveries show that the amount
      of bone that is formed around beta-tricalcium phosphate and bovine hydroxyapatite
      is clearly superior to the bioactive glasses. Both the lumen diameter and the
      number of vessels were slightly increased in favor of beta-tricalcium phosphate.
      Conclusion: We can conclude that bone substitutes as bovine bone and beta
      tricalcium phosphate have significant increased angiogenesis (and subsequent
      improved osteogenesis) compared to the bioactive glass. In our study, significant
      angiogenesis is linked with a greater tissue formation, indicating that in bone
      engineering with the allografts we used, inflammation has more benefic effects,
      the catabolic action being exceeded by the tissue formation.

PMID- 30298139
TI  - Spatially-Compact MR-Guided Kernel EM for PET Image Reconstruction.
AB  - Positron emission tomography (PET) is a highly sensitive functional and molecular
      imaging modality which can measure picomolar concentrations of an injected
      radionuclide. However, the physical sensitivity of PET is limited, and reducing
      the injected dose leads to low count data and noisy reconstructed images. A
      highly effective way of reducing noise is to reparameterise the reconstruction in
      terms of MR-derived spatial basis functions. Spatial basis functions derived
      using the kernel method have demonstrated excellent noise reduction properties
      and maintain shared PET-MR detailed structures. However, as previously shown in
      the literature, the MR-guided kernel method may lead to excessive smoothing of
      structures that are only present in the PET data. This work makes two main
      contributions in order to address this problem: first, we exploit the potential
      of the MR-guided kernel method to form more spatially-compact basis functions
      which are able to preserve PET-unique structures, and secondly, we consider
      reconstruction at the native MR resolution. The former contribution notably
      improves the recovery of structures which are unique to the PET data. These
      adaptations of the kernel method were compared to the conventional implementation
      of the MR-guided kernel method and also to MLEM, in terms of ability to recover
      PET unique structures for both simulated and real data. The spatially-compact
      kernel method showed clear visual and quantitative improvements in the
      reconstruction of the PET unique structures, relative to the conventional kernel
      method for all sizes of PET unique structures investigated, whilst maintaining to
      a large extent the impressive noise mitigating and detail preserving properties
      of the conventional MR-guided kernel method. We therefore conclude that a
      spatially-compact parameterisation of the MR-guided kernel method, should be the
      preferred implementation strategy in order to obviate unnecessary losses in PET
      unique details.

PMID- 30298140
TI  - Maternal Plasma Concentrations of Per- and polyfluoroalkyl Substances and
      Breastfeeding Duration in the Norwegian Mother and Child Cohort.
AB  - Background: Per- and polyfluoroalkyl substances (PFASs) have been widely
      produced, many of them persist in the environment, and have been associated with
      various health effects. Previous studies have identified inverse associations
      between perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and
      breastfeeding duration, but have been limited in investigation of other PFASs.
      Methods: We measured the associations between plasma concentrations of 9
      different PFASs and cessation of breastfeeding before 3 and 6 complete months
      using women from the Norwegian Mother and Child Cohort Study (MoBa). The study
      population includes 1716 primarily nulliparous women from two previous studies of
      MoBa participants, enrolled from 2003-2007. The association was measured using
      Cox proportional hazards model. Mixtures analyses were performed using Elastic
      net regularization to identify interactive effects and control for co-pollutant
      confounding. Results: Concentrations of PFASs in this population were lower than
      concentrations in the previous studies on this topic. We found associations
      between increasing concentrations of perfluorononanoic acid (PFNA),
      perfluorodecaconic acid (PFDA), perfluoroundecanoic acid (PFUnDA) and decreased
      breastfeeding cessation (increased duration). The strongest associations were
      seen between PFDA and PFUnDA and cessation before 3 months: (both hazard ratios =
      0.73, 95% confidence intervals: 0.62, 0.86). In our population, the other PFASs
      appeared to be unassociated with breastfeeding cessation. The mixtures analyses
      identified meaningful interactions between PFUnDA:PFDA, perfluorohexane sulfonate
      (PFHXS):PFOA and PFOA:PFOS. Conclusions: The identification of associations
      between previously unexamined PFASs concentrations and increased breastfeeding
      duration is novel and may be explained by differences in transplacental transfer
      rates.

PMID- 30298141
TI  - MoodLight: Exploring Personal and Social Implications of Ambient Display of
      Biosensor Data.
AB  - MoodLight is an interactive ambient lighting system that responds to biosensor
      input related to an individual's current level of arousal. Changes in levels of
      arousal correspond to fluctuations in the color of light provided by the system,
      altering the immediate environment in ways intimately related to the user's
      private internal state. We use this intervention to explore personal and social
      implications of the ambient display of biosensor data. This study provides
      greater understanding of the ways in which the representations of personal
      informatics, with a focus on ambient feedback, influence our perceptions of
      ourselves and those around us.

PMID- 30298142
TI  - Alcohol and Marijuana use in Undergraduate Males: Between- and Within-Person
      Associations with Interpersonal Conflict.
AB  - Background: Among college students, interpersonal conflict with others is a
      common, yet stressful negative interpersonal experience. Research suggests that
      drinking episodes may contribute to the occurrence of conflict. Marijuana use,
      independently or in conjunction with alcohol, may also influence the likelihood
      of subsequent conflict. Objectives: We considered the temporal effects of
      independent and simultaneous alcohol and marijuana use episodes on the occurrence
      of interpersonal conflict. Use of multilevel modeling allowed us to distinguish
      the within-person effects of substance use from between-person differences in
      frequency of use. Methods: Within a sample of 427 college freshman males over 56
      days of daily reports, we examined the independent and interactive effects of
      episodes of alcohol and marijuana on the odds of conflict within the next 1-, 2-,
      3-, and 4 hours. Results: Multilevel modeling analyses showed that drinking
      episodes increased the likelihood of conflict occurring within the next 1, 2, 3,
      and 4 hours. Marijuana had weaker positive effects, significant only within the 2
      hour window. There were no alcohol by marijuana interaction effects in any
      analysis. Conclusions/Importance: Both marijuana and alcohol independently
      increased the likelihood of interpersonal conflict; however, the marijuana effect
      appeared less robust. As marijuana use becomes more normative and accessible for
      college students, it is important to understand the extent to which marijuana use
      results in negative consequences and the contexts under which these effects
      unfold.

PMID- 30298143
TI  - Synthesis and thermo-responsive behavior of helical polyacetylenes derived from
      proline.
AB  - A series of optically active helical poly[(S)-2-ethynyl-N-aliphatic
      acylpyrrolidine] were efficiently synthesized from a commercially available
      biomass-based starting material, and that bearing a short propionyl substituent
      exhibited an unexpected lower critical solution temperature in an aqueous
      solution with a narrow phase-transition window and a small hysteresis.

PMID- 30298144
TI  - Development of a biomimetic liver tumor-on-a-chip model based on decellularized
      liver matrix for toxicity testing.
AB  - Cancer poses a great health threat to both developed and developing countries,
      and anti-cancer drugs are of important interest for improved clinical outcomes.
      Although tumor-on-a-chip technologies offer a feasible approach to screening drug
      toxicity, their capability to mimic the native tumor microenvironment (TME) is
      still limited. For better mimicry of the TME, we developed a biomimetic three
      dimensional (3D) liver tumor-on-a-chip with the integration of essential
      components derived from decellularized liver matrix (DLM) with gelatin
      methacryloyl (GelMA) in a microfluidics-based 3D dynamic cell culture system. The
      biomimetic liver tumor-on-a-chip based on the integration of DLM components with
      GelMA, as opposed to GelMA only, had an increased capability to maintain cell
      viability and to enhance hepatocyte functions under flow conditions. The improved
      performance of the DLM-GelMA-based tumor-on-a-chip may be attributed to the
      provision of biochemical factors (e.g., growth factors), the preservation of
      scaffold proteins, and the reestablishment of biophysical cues (e.g., stiffness
      and shear stress) for better recapitulation of the 3D liver TME. Furthermore,
      this DLM-GelMA-based tumor-on-a-chip exhibited linear dose-dependent drug
      responses to the toxicity of acetaminophen and sorafenib. Taken together, our
      study demonstrates that the DLM-GelMA-based biomimetic liver tumor-on-a-chip
      better mimics the in vivo TME and holds great promise for a breadth of
      pathological and pharmacological studies.

PMID- 30298145
TI  - Binding of the atomic cations hydrogen through argon to water and hydrogen
      sulfide.
AB  - Water and hydrogen sulfide will bind with every atomic cation from the first
      three rows of the periodic table. While some atoms bind more tightly than others,
      explicitly correlated coupled cluster theory computations show that energy is
      required to be put into the system in order to dissociate these bonds even for
      noble gas atoms. The most promising systems have shallow entrance potential
      energy surfaces (PESs) that lie above deeper wells of a different spin. These
      wells are shown explicitly for H2OO+, H2SS+, and H2OS+ where relaxed PESs of the
      heavy atom bond lengths indicate that quartet states will cross more deeply-bound
      doublet states allowing for relatively easy association but much more difficult
      dissociation. In astrophysical regions that are cold and diffuse, such
      associations could lead to the formation of novel molecules utilizing water (or
      H2S) as the building blocks of more rich subsequent chemistry. Recent work has
      hypothesized that oxywater (H2OO) may be an intermediate in the formation of
      molecular oxygen in comets, and this work supports such a conclusion at least
      from a molecular cation perspective.

PMID- 30298146
TI  - Photochemical route for synthesizing Co-P alloy decorated ZnIn2S4 with enhanced
      photocatalytic H2 production activity under visible light irradiation.
AB  - A series of amorphous Co-P alloy modified ZnIn2S4 composite samples were
      synthesized through a one-step photochemical method. The as-prepared samples were
      systematically characterized and the photocatalytic activity for H2 production
      under visible-light irradiation was investigated. It was found that the Co
      P/ZnIn2S4 composite samples exhibited higher photocatalytic activity, which is 44
      times higher than that of pure ZnIn2S4 and higher than that of the 1 wt%
      Pt/ZnIn2S4 sample. After modifying with amorphous Co-P alloy, the composite
      samples showed enhanced photocurrent, reduced photoelectric impedance, weakened
      fluorescence intensity and extended fluorescence lifetime, which accelerate the
      separation and transfer of photoinduced charge effectively, thus improving the
      catalytic activity of the composite sample. This work could provide a new
      strategy for the design and synthesis of low-cost, high-efficiency composite
      materials for photocatalytic hydrogen evolution and is promising for energy
      conversion and utilization.

PMID- 30298147
TI  - Three-dimensional image based modelling of transport parameters in lithium-sulfur
      batteries.
AB  - An elemental sulfur electrode was imaged with X-ray micro and nano computed
      tomography and segmented into its constituent phases. Morphological parameters
      including phase fractions and pore and particle size distributions were
      calculated directly from labelled image data, and flux based simulations were
      performed to determine the effective molecular diffusivity of the pore phase and
      electrical conductivity of the conductive carbon and binder phase, Deff and
      sigmaeff, that can be used as an input for Li-S battery modelling. In addition to
      its crucial role in providing electrical conductivity within the sulfur
      electrode, the intrinsic porosity of the carbon binder domain was found to
      significantly influence Li-ion transport within the electrode. Neglecting this
      intrinsic porosity results in an overestimation of the electrical conductivity
      within the sulfur electrode, and an underestimation of the tortuosity of the Li
      ion conducting phase by ca. 56%. The derivation of effective transport parameters
      directly from image data may aid in the development of more realistic models of
      Li-S battery systems by reducing the reliance on empirical correlations, and the
      uncertainties arising from assumptions made in these correlations.

PMID- 30298148
TI  - Correction: Fe-Catalyzed three-component carboazidation of alkenes with alkanes
      and trimethylsilyl azide.
AB  - Correction for 'Fe-Catalyzed three-component carboazidation of alkenes with
      alkanes and trimethylsilyl azide' by Wei-Yu Li et al., Chem. Commun., 2018, DOI:
      .

PMID- 30298150
TI  - A novel mitochondrial-targeting near-infrared fluorescent probe for imaging gamma
      glutamyl transpeptidase activity in living cells.
AB  - gamma-Glutamyl transpeptidase (GGT) plays an essential role in regulating
      cellular glutathione and cysteine homeostasis, and its abnormal elevation is
      associated with different diseases including cancers. Here a novel mitochondrial
      targeting near-infrared fluorescent probe was designed for GGT by conjugating
      glutamate acid to a newly synthesized amine hemicyanine fluorophore. The
      fluorescent probe was initially non-emissive due to the formation of an amide
      bond which destroyed the electronic-donating ability of the amine moiety and
      disrupted the push-pull structure. GGT-mediated cleavage of the gamma-glutamyl
      bond regenerated the initial fluorophore with distinct intramolecular charge
      transfer (ICT) and activated the fluorescence signal. The fluorescent probe
      displayed a linear relationship to the concentration of GGT in the range of 1.0
      90 U L-1, with an estimated limit of detection (LOD) of 0.4 U L-1. Its ability to
      target and image mitochondrial GGT activity was demonstrated in living cells with
      high specificity and fast response. We believe our near-infrared fluorescent
      probe could have great potential in imaging mitochondrial GGT activity and
      elucidating GGT-associated pathological consequences in living cells and even
      small animal models.

PMID- 30298151
TI  - Two-dimensional pi-conjugated metal-organic nanosheets as single-atom catalysts
      for the hydrogen evolution reaction.
AB  - The design and synthesis of electrocatalysts with controllable active sites are
      highly desirable for producing hydrogen. Inspired by the experimental realization
      of two-dimensional metal-organic framework (2D-MOF) nanosheets, a computational
      screening was performed to find out the optimal single-atom catalysts for the
      hydrogen evolution reaction (HER) from 36 2D-MOFs composed of transition metal
      and benzene-like molecular ligands. Through first-principles calculations, six
      configurations were identified as potential catalysts for the HER with
      performance comparable to those of Pt-based catalysts due to the near-zero Gibbs
      free energy and favourable activation barriers originating from their appropriate
      d-orbital bonding mechanism with atomic hydrogen.

PMID- 30298149
TI  - LY2874455 potently inhibits FGFR gatekeeper mutants and overcomes mutation-based
      resistance.
AB  - The chemical compound LY2874455 has the potential to overcome drug resistance
      driven by FGFR gatekeeper mutations. X-ray crystallographic studies provide the
      structural explanation for why this compound is effective against the FGFR
      gatekeeper mutations.

PMID- 30298152
TI  - Graphene-silicon-on-insulator (GSOI) Schottky diode photodetectors.
AB  - Graphene-silicon (GS) Schottky junctions have been demonstrated as an efficient
      architecture for photodetection. However, the response speed of such devices for
      free space light detection has so far been limited to 10s-100s of kHz for
      wavelength lambda >500 nm. Here, we demonstrate GS Schottky junction
      photodetectors fabricated on a silicon-on-insulator substrate (SOI) with response
      speeds approaching 1 GHz, attributed to the reduction of the photo-active silicon
      layer thickness to 10 MUm and with it a suppression of speed-limiting diffusion
      currents. Graphene-silicon-on-insulator photodetectors (GSOI-PDs) exhibit a
      negligible influence of wavelength on response speed and only a modest compromise
      in responsivities compared to GS junctions fabricated on bulk silicon. Noise
      equivalent-power (NEP) and specific detectivity (D*) of GSOI photodetectors are
      14.5 pW and 7.83 * 1010 cm Hz1/2 W-1, respectively, in ambient conditions. We
      further demonstrate that combining GSOI-PDs with micro-optical elements formed by
      modifying the surface topography enables engineering of the spectral and angular
      response.

PMID- 30298153
TI  - Monitoring of food spoilage by high resolution THz analysis.
AB  - High resolution rotational Terahertz (THz) spectroscopy has been widely applied
      to the studies of numerous polar gas phase molecules, in particular volatile
      organic compounds (VOCs). During the storage of foodstuffs packed under a
      protective atmosphere, microbial activity will lead to the generation of a
      complex mixture of trace gases that could be used as food spoilage indicators.
      Here we have demonstrated that the THz instrumentation presently available
      provides sufficient sensitivity and selectivity to monitor the generation of
      hydrogen sulfide (H2S) in the headspace of packed Atlantic salmon (Salmo salar)
      fillet portions. A comprehensive comparison was made using selective-ion flow
      tube mass spectrometry (SIFT-MS) in order to validate the THz measurements and
      the protocol. The detectivity of a range of alternative compounds for this
      application is also provided, based on the experimental detection limit observed
      and molecular spectroscopic properties. Molecules like ethanol, methyl mercaptan
      and ammonia are suitable indicators with the presently available sensitivity
      levels, while dimethyl sulfide, acetone and butanone may be considered with a
      sensitivity improvement of 2 orders of magnitude.

PMID- 30298154
TI  - Cyclic Pt3Ag33 and Pt3Au12Ag21 nanoclusters with M13 icosahedra as building
      blocks.
AB  - In this work, we report a controlled self-assembly of three M13 icosahedral
      building-blocks into cyclic Pt3Ag33 or Pt3Au12Ag21 nanoclusters. Compared to the
      previously reported Pt2Ag23 and Pt1Ag12 nanoclusters, the Pt3Ag33 nanoclusters
      exhibit a red-shift in both the optical absorption and photoluminescence due to
      the assembly of an additional Pt1Ag12 icosahedron.

PMID- 30298155
TI  - Doping effect of transition metals (Zr, Mn, Ti and Ni) on well-shaped
      CuO/CeO2(rods): nano/micro structure and catalytic performance for selective
      oxidation of CO in excess H2.
AB  - A series of CuO/CeM(rod) catalysts doped by transition metals were prepared and
      systematically characterized. The introduction of Mn and Ti plays a significant
      role in promoting the catalytic performance of the CuO/CeO2(rod) catalyst for the
      preferential oxidation of CO in H2-rich gas, while the doping with Zr basically
      maintains the same catalytic activity and Ni leads to a negative influence. Mn
      and Ti additives remarkably enrich the formation of defect structures and promote
      copper ion incorporation into the surface of CeM(rod), which greatly facilitates
      the generation of strong interfacial copper-ceria interaction in CuO/CeMn(rod)
      and CuO/CeTi(rod). In addition, CuO/CeMn(rod) possesses excellent surface oxygen
      mobility at low temperature due to the existence of manganese species with
      multiple valence states and todorokite species. The Ce-doped perovskite structure
      (Na0.5Ce0.5TiO3) further adjusts the oxygen vacancy in CuO/CeTi(rod) and anchors
      copper oxide species with strong interactions. Although a homogeneous solid
      solution is formed in CeZr(rod) with increased amounts of oxygen vacancies, the
      interaction between copper and ceria species in the interface of CuO/CeZr(rod)
      remains the same as with CuO/CeO2(rod). The addition of Ni impairs the dispersion
      of copper oxide and weakens the copper-ceria interaction, which damages the
      catalytic performance of CuO/CeNi(rod).

PMID- 30298156
TI  - Triplet photosensitization mechanism of thymine by an oxidized nucleobase: from a
      dimeric model to DNA environment.
AB  - Nucleic acids are constantly exposed to external agents that can induce chemical
      and photochemical damage. In spite of the great advances achieved in the last
      years, some molecular mechanisms of DNA damage are not completely understood yet.
      A recent experimental report (I. Aparici-Espert et al., ACS Chem. Biol. 2018, 13,
      542) proved the ability of 5-formyluracil (ForU), a common oxidatively generated
      product of thymine, to act as an intrinsic sensitizer of nucleic acids, causing
      single strand breaks and cyclobutane pyrimidine dimers in plasmid DNA. In the
      present contribution, we use theoretical methodologies to study the triplet
      photosensitization mechanism of thymine exerted by ForU in a model dimer and in
      DNA environment. The photochemical pathways in the former system are described
      combining the CASPT2 and TD-DFT methods, whereas molecular dynamics simulations
      and QM/MM calculations are employed for the DNA duplex. It is unambiguously shown
      that the 1n,pi* state localised in ForU mediates the population of the triplet
      manifold, most likely the 3pi,pi* state centred in ForU, whereas the 3pi,pi*
      state localized in thymine can be populated via triplet-triplet energy transfer
      given the small energy barrier of <0.23 eV determined for this pathway.

PMID- 30298157
TI  - Third generation antibody discovery methods: in silico rational design.
AB  - Owing to their outstanding performances in molecular recognition, antibodies are
      extensively used in research and applications in molecular biology, biotechnology
      and medicine. Recent advances in experimental and computational methods are
      making it possible to complement well-established in vivo (first generation) and
      in vitro (second generation) methods of antibody discovery with novel in silico
      (third generation) approaches. Here we describe the principles of computational
      antibody design and review the state of the art in this field. We then present
      Modular, a method that implements the rational design of antibodies in a modular
      manner, and describe the opportunities offered by this approach.

PMID- 30298158
TI  - Porous coordination/covalent hybridized polymers synthesized from pyridine-zinc
      coordination compound and their CO2 capture ability, fluorescence and selective
      response properties.
AB  - Currently, porous polymers are mainly synthesized by linking coordination or
      organic covalent bonds. In this study, we propose the synthesis of a porous
      coordination/covalent hybridized polymer from di(4-vinylpyridine)-dichloro-zinc
      (ZnVP2) by "coordination-polymerization" method. The resulting porous polymer
      demonstrated CO2 capture ability and multi-responsive properties.

PMID- 30298159
TI  - Expeditious synthesis of multisubstituted indoles via multiple hydrogen
      transfers.
AB  - Described herein is the expeditious construction of multi-substituted indole
      skeletons via multiple hydrogen transfers. When ortho-amino ketoesters were
      treated with a catalytic amount of TiCl4 in the presence of 1.0 equivalent of
      dehydrating reagent, three types of hydrogen transfer processes ([1,5]-hydride
      shift, proton transfer, and [1,2]-hydride shift) occurred to give various 3
      alkoxycarbonylindoles. Further study revealed that a [1,2]-alkyl shift instead of
      a [1,2]-hydride shift proceeded to afford 3-alkylindoles from the substrates with
      an amino group having tertiary carbons adjacent to a nitrogen atom.

PMID- 30298160
TI  - QCM detection of molecule-nanoparticle interactions for ligand shells of varying
      morphology.
AB  - Nanoparticles (NP) have widespread applications from sensing to drug delivery
      where much behavior is determined by the nature of the surface and the resulting
      intermolecular interactions with the local environment. Ligand mixtures enable
      continuously tunable behavior where both the composition and morphology influence
      molecular interactions. Mixed ligand shells form multiple morphologies ranging
      from Janus to patchy and stripe-like with varying domain dimensions. Solvent-NP
      interactions are generally measured by solubility measures alone. Here we develop
      a quartz crystal microbalance (QCM) approach to more broadly quantify molecule-NP
      interactions via vapor phase uptake into solid NP-films independent from
      solvation constraints. The composition and morphology of mixed ligand shells were
      found to exhibit pronounced non-monotonic behavior that deviated from continuum
      thermodynamics, highlighting the influence of ligand morphology upon
      absorption/adsorption. Alkyl and perfluorinated thiols were used as a model case
      with constant core-size distribution. The ligand morphology was determined by 19F
      NMR. Molecule uptake into NPs was measured with five benzene derivatives with
      varied degree of fluorination. For the cases examined, QCM measurements revealed
      enhanced uptake for patchy morphologies and suppressed uptake for stripe-like
      morphologies. These results contrast with insights from solubility measures alone
      where QCM sometimes identified significant molecular uptake of poor solvents.
      This QCM method thus provides new insights to molecule-NP interactions
      independent of the solvation shell.

PMID- 30298161
TI  - Computational insights into the inhibition of beta-haematin crystallization by
      antimalarial drugs.
AB  - During the red blood cell phase of their life cycle, malaria parasites digest
      their host's haemoglobin, with concomitant release of potentially toxic iron(iii)
      protoporphyrin IX (FePPIX). The parasites' strategy for detoxification of FePPIX
      involves its crystallization to haemozoin, such that the build-up of free haem in
      solution is avoided. Antimalarial drugs of both historical importance and current
      clinical use are known to be capable of disrupting the growth of crystals of beta
      haematin, which is the synthetic equivalent of haemozoin. Hence, the disruption
      of haemozoin crystal growth is implicated as a possible mode of action of such
      drugs. However, the details of beta-haematin crystal poisoning at the molecular
      level have yet to be fully elucidated. In this study, we have used a combination
      of density functional theory (DFT) and molecular modelling to examine the
      possible modes of action of ten different antimalarial drugs, including quinine
      type aliphatic alcohols, amodiaquine-type phenols, and chloroquine-type aliphatic
      diamines. The DFT calculations indicate that each of the drugs can form at least
      one molecular complex with FePPIX. These complexes have 1 : 1 or 2 : 1 FePPIX :
      drug stoichiometries and all of them incorporate Fe-O bonds, formed either by
      direct coordination of a zwitterionic form of the drug, or by deprotonation of
      water. Most of the drugs can form more than one such complex. We have used the
      DFT model structures to explore the possible formation of a monolayer of each
      drug-haem complex on four of the beta-haematin crystal faces. In all cases, the
      drug complexes can form a monolayer on the fast-growing {001} and {011} faces,
      but not on the slower growing {010} and {100} faces. Additional modelling of the
      chloroquine and quinidine complexes shows that individual molecules of these
      species can also obstruct the growth of new layers on other crystal faces. The
      implications of these observations for antimalarial drug development are
      discussed.

PMID- 30298162
TI  - Ab initio interatomic potentials and transport properties of alkali metal (M = Rb
      and Cs)-rare gas (Rg = He, Ne, Ar, Kr, and Xe) media.
AB  - We performed a first principle systematic calculation on the adiabatic potential
      energy curves (PECs) of alkali metal (M = Rb and Cs) - rare gas (Rg = He, Ne, Ar,
      Kr, and Xe) van der Waals molecules over a wide range of interatomic distance R.
      All electron basis sets of triple and quadruple zeta valence quality were used
      for the He, Ne, Ar and Kr atoms. Scalar relativistic effects were taken into
      account for the heavy Rb, Cs and Xe atoms by means of Dirac-Fock effective core
      potentials. The correlated ground state energies have been obtained within the
      framework of the spin unrestricted open-shell coupled cluster method, with
      perturbative treatment of triple excitations. The electronic energies were
      corrected for the basis set superposition error (BSSE) using the counterpoise
      method. Energies were extrapolated to the complete basis set (CBS) limit using a
      two-point scheme. The energy convergence towards the CBS limit was monitored by
      the saturation of the dummy atom basis set that included bond functions centered
      at the midpoint of the interatomic distance. The ab initio point-wise PEC was
      followed to small R to the point where the energy was 0.5 Hartree above the
      dissociation limit. A Morse long-range (MLR, UM Rg(R)) potential possessing the
      correct asymptotic behavior at R -> infinity was fitted to the single point
      energies. The resulting set of fully analytical MLR potentials was then used to
      evaluate classical collision integrals over a wide range of collision energies.
      By this means, diffusion coefficients (DM Rg(T)) were predicted as functions of
      the translation temperature T <= 3000 K. The reliability of the present ab initio
      UM Rg(R) and DM Rg(T) functions was accessed through a comparison with previous
      theoretical and experimental results.

PMID- 30298163
TI  - Continuous flow biodiesel production from wet microalgae using a hybrid thin film
      microfluidic platform.
AB  - A novel continuous flow turbo-thin film device (T2FD) has been developed. The
      microfluidic platform is effective in high yielding production of biodiesel from
      wet microalgae at room temperature under continuous flow conditions. These
      findings open the possibility of cost effective production of biodiesel directly
      from wet microalgae.

PMID- 30298164
TI  - Mesoporous S doped Fe-N-C materials as highly active oxygen reduction reaction
      catalyst.
AB  - Mesoporous Fe, S, N doped carbon (m-FeSNC) materials have been successfully
      synthesized by pyrolysis of polymerized o-phenylenediamine using binary
      initiators. It exhibited high electrocatalytic activity towards oxygen reduction
      reaction, and zinc-air battery with higher performance has been fabricated using
      m-FeSNC than using commercial Pt/C.

PMID- 30298165
TI  - Applications of crystal structure prediction - inorganic and network structures:
      general discussion.

PMID- 30298166
TI  - Synthesis of the core structure of phalarine.
AB  - The core skeleton of phalarine was rapidly synthesised through novel palladium
      catalysed dearomative spirocyclisation and a palladium-catalysed Wacker
      carbonylative cyclisation cascade. The two key steps allowed for the efficient
      construction of a tricyclic propeller skeleton bearing contiguous
      tetrasubstituted carbon centres, within 3 steps from a topologically planar
      precursor.

PMID- 30298167
TI  - Time to Address "Frailty Creepage" in the Canadian Healthcare System.

PMID- 30298168
TI  - Implementing Frailty Measures in the Canadian Healthcare System.
AB  - Canadian healthcare is changing to include individuals living with frailty, but
      frailty must be better operationalized and better framed by sound data standards
      and policy. Frailty results from deficit accumulation in multiple body systems,
      with exaggerated vulnerability to external stressors. A growing consensus on
      defining frailty sets the stage for consensus on operationalization and
      widespread implementation in care settings. Frailty measurement is not yet
      integrated into daily clinical practice in Canada. Here, we will present how this
      integration might occur. We hope to demonstrate that implementation must appeal
      to inter-professional practice needs in different settings or circumstances. In
      some settings, methods for frailty case finding are expected to evolve as deemed
      to be most appropriate to the front-line users. In this "hands-off" approach,
      care providers, supported by emerging knowledge translation on frailty
      operationalization, would be informed by their setting and local practices to
      establish patterns of ad hoc case finding and component definition of frailty.
      This more nimble case finding strategy would be opportunistic, and would appeal
      to expert clinicians and self-directed teams who emphasize an individualized
      health care experience for their patients. In other settings, we can shape
      frailty case finding by building care algorithms around existing standardized
      practices and data repositories, leading to a systematic application of frailty
      measures and a more coordinated process of component definition and care
      protocols. Here, recommended instruments and data standards must be endorsed by
      health networks locally, provincially and nationally. The interRAI suite of
      assessment instruments has pan-Canadian standards in place and its pervasiveness
      makes it the most obvious starting point, especially in home care and long-term
      care. We anticipate the evolution of an integrated model informed by stakeholders
      and settings, where policy makers focus on system supports for frailty case
      finding, while front-line clinicians use case finding strategies to pinpoint and
      act on key frailty components.

PMID- 30298169
TI  - Social and societal implications of frailty, including impact on Canadian
      healthcare systems.
AB  - Frailty has many social and societal implications. Social circumstances are key
      both as contributors to frail older adults' health outcomes and as practical
      facilitators or barriers to intervention and supports. Frailty also has important
      societal implications for health systems and social care policy. In this
      discussion paper, we use a social ecology framework to consider the social and
      societal implications and impact of frailty at each level, from the individual,
      through relationships with family and friend caregivers, institutions, health
      systems, neighborhoods and communities, to society at large. We conclude by
      arguing that attention to these issues at a policy level is critical. We identify
      three target actions: 1) Social dimensions of frailty should be systematically
      considered when frailty is assessed. 2) Action is needed at the level of policies
      and programs to improve support for caregivers. 3) Policy review across all
      portfolios will benefit from a social frailty lens.

PMID- 30298170
TI  - Ethical and Legal Implications of Frailty Screening.
AB  - Goals of screening for frailty include (a) promoting healthy aging, (b)
      addressing frailty with preventive and targeted interventions, (c) better
      aligning social and medical responses to frailty with the needs of frail older
      adults and (d) preventing harms to frail older adults from excessive and
      inappropriate medical interventions that are insensitive to the implications of
      frailty. However, the medicalization of frailty and outcomes of the screening
      process also risk harming frail older adults and their autonomy through
      stereotyping and by legitimizing denial of care. This risk of harm gives rise to
      ethical and legal questions and considerations that this paper addresses. Frailty
      screening that is ethically defensible will situate and support healthcare that
      is consistent with people's needs, circumstances and capacity to benefit from the
      care provided. We also call for an informed consent process that incorporates
      supported or shared decision making in order to protect the autonomy of frail
      older adults.

PMID- 30298171
TI  - Policy and Economic Considerations for Frailty Screening in the Canadian
      Healthcare System.
AB  - Canada faces significant policy and economic challenges related to healthcare for
      frail older adults. Annual per capita healthcare costs for people over age 65 are
      five times those for people under 65. Flat economic growth and an aging workforce
      decrease tax revenue, which funds 70% of health spending. Governments are
      shifting policy to enhance person-centered care and shifting spending from
      hospitals to primary and community care. Recognizing that frailty and evidence
      based frailty screening can contribute directly to reform initiatives, what are
      the policy and economic considerations, both nationally and internationally,
      around frailty screening that will benefit patients, families and/or the wider
      health system? Based on key informant interviews, we present recommendations for
      approaching policy and economic challenges in frailty through the following
      healthcare policy instruments: financing, funding, legislation, regulation,
      technology, interdisciplinary care, person-centered service and health promotion.

PMID- 30298172
TI  - Improving End-of-Life Care and Advance Care Planning for Frail Older Adults in
      Canad.
AB  - We present five Key Concepts that describe priorities for improving end-of-life
      care for frail older adults in Canada, and recommendations based on each Key
      Concept. Key Concept #1: Our end-of-life care system is focused on cancer, not
      frailty. Key Concept #2: We need better strategies to systematically identify
      frail older adults who would benefit from a palliative approach. Key Concept #3:
      The majority of palliative and end-of-life care will be, and should be, provided
      by clinicians who are not palliative care specialists. Key Concept #4:
      Organizational change and innovative funding models could deliver far better end
      of-life care to frail individuals for less than we are currently spending. Key
      Concept #5: Improving the quality and quantity of advance care planning for frail
      older adults could reduce unwanted intensive care and costs at the end of life,
      and improve the experience for individuals and family members alike.

PMID- 30298173
TI  - Nutritional Intervention in Sarcopenia: Report from the International Conference
      on Frailty and Sarcopenia Research Task Force.
AB  - Research suggests that poor nutrition is an underlying cause of sarcopenia and
      frailty, and that dietary interventions may prevent or treat age-related loss of
      muscle mass and strength. In February 2018, the International Conference on
      Frailty and Sarcopenia Research Task Force explored the current status of
      research on nutritional interventions for sarcopenia as well as gaps in
      knowledge, including whether nutritional supplements must be combined with
      physical activity, and the role of nutritional intervention in sarcopenic obese
      individuals. The lack of consistency across trials in terms of target
      populations, assessments, health-care settings, control groups, and choice of
      outcomes has made it difficult to draw meaningful conclusions from recent
      studies. The Task Force recommended large randomized controlled trials in
      heterogeneous, real-world populations to enable sub-group analysis. The field
      also needs to reach consensus on what outcomes are most meaningful and what
      represents clinically meaningful change.

PMID- 30298174
TI  - Association between High Levels of Parathyroid Hormone and Frailty: The Nepean
      Osteoporosis and Frailty (NOF) Study.
AB  - BACKGROUND: Frailty is associated with poor outcomes hence identification of
      risks factors is pivotal. Since the independent role of parathyroid hormone (PTH)
      in frailty remains unexplored, we aimed to determine this in a population of
      older individuals with a history of falling. DESIGN: Cross-sectional study.
      SETTING: Falls and Fracture Clinic, Nepean Hospital (Penrith, Australia).
      PARTICIPANTS: 692 subjects (mean age=79, 65% women) assessed between 2009-2015.
      MEASUREMENTS: Assessment included clinical examination, mood, nutrition, grip
      strength, gait velocity, bone densitometry and posturography. Chemistry included
      serum PTH, calcium, vitamin D (25(OH)D3), creatinine and albumin. Normocalcemic
      subjects were divided into 4 groups: (1) Normal: 25(OH)D3 >50nmol/L and PTH
      between 1.6-6.8pmol/L; (2) PTH responsive: low 25(OH)D3 (<50nmol/L) and high PTH
      (>6.8pmol/L); (3) PTH unresponsive: low 25(OH)D3 and normal PTH; (4) Hyper PTH
      (>6.8pmol/L) with normal 25(OH)D3. Frailty was defined using Fried's criteria.
      Difference between the groups was assessed using one-way ANOVA and X2 analysis.
      Multinomial logistic regression evaluated the association between the groups and
      the number of Fried's criteria adjusted for age, BMI, renal function, 25(OH)D3
      levels, and albumin. RESULTS: 22.6% subjects had high PTH levels (>6.8pmol/L).
      All subjects in the high PTH groups had significantly lower grip strength, gait
      velocity, limits of stability, and higher BMI. The PTH responsive group had a
      higher risk of pre-frailty (beta=3.8, 95% CI = 3.42 - 5.22, p? 0.01) and frailty
      (beta=8.26, 95% CI = 2.8-16.1, p<0.01). The risk of frailty was also higher in
      the Hyper PTH group (beta=2.3, 95% CI = 1.74-4.32, p<0.01). CONCLUSION: We have
      reported an independent association of high PTH levels with high number of falls
      and with the clinical components of physical frailty in community dwelling older
      persons. Our results suggest a possible role of PTH in frailty that deserves
      further exploration.

PMID- 30298177
TI  - Older Adults' Perceptions of the Built Environment and Associations with Frailty:
      A Feasibility and Acceptability Study.
AB  - It is essential to evaluate frail older adults understanding and execution of
      survey tools to improve data quality and accurate representation in research. The
      study tested the feasibility and acceptability of a survey that assesses various
      measures of functional status in frail older people. The study evaluated: 1)
      recruitment rate; 2) time to complete questionnaires and difficulties
      encountered; and 3) acceptability by participants. Validated tools including:
      FRAIL Scale, EuroQoL 5D-5L, Charlson's Comorbidities Index, Baecke's Physical
      Activity Questionnaire, Life-Space Assessment, Katz and Lawton ADL and NEWS
      Walkability Scale were assessed. Twenty-five older patients (63% recruitment
      rate) of a post-acute restorative program (residential Transition Care Program)
      in Adelaide, South Australia were interviewed. Although not statistically
      different, time to complete the overall questionnaire differed between robust,
      pre-frail and frail participants. Overall, the survey was considered acceptable
      and feasible, with consideration with NEWS and Life-Space assessment regarding
      length, phrasing and layout.

PMID- 30298175
TI  - The Role of Ultrasound as a Diagnostic Tool for Sarcopenia.
AB  - Sarcopenia is the progressive loss of skeletal mass and strength, particularly in
      older adults, with consequent reduction in function and independence. Changing
      population demographics, have resulted in increased prevalence of sarcopenia and
      this is associated with a considerable economic burden. Whilst simple, effective,
      non-intrusive management of this condition exists, no routine diagnosis takes
      place either in the UK or in many other countries, partly due to an absence of
      pragmatic clinical diagnostic tools to support the early identification of the
      syndrome. This position paper aims to provide a short overview proposing the
      potential case for developing ultrasound as a new and alternative diagnostic tool
      for identifying sarcopenia.

PMID- 30298176
TI  - Single Physical Performance Measures Cannot Identify Geriatric Outpatients with
      Sarcopenia.
AB  - BACKGROUND: Sarcopenia is highly prevalent in the older population and is
      associated with several adverse health outcomes. Equipment to measure muscle mass
      and muscle strength to diagnose sarcopenia is often unavailable in clinical
      practice due to the related expenses while an easy physical performance measure
      to identify individuals who could potentially have sarcopenia is lacking.
      OBJECTIVES: This study aimed to assess the association between physical
      performance measures and definitions of sarcopenia in a clinically relevant
      population of geriatric outpatients. DESIGN, SETTING AND PARTICIPANTS: A cross
      sectional study was conducted, consisting of 140 community-dwelling older adults
      that were referred to a geriatric outpatient clinic. No exclusion criteria were
      applied. MEASUREMENTS: Physical performance measures included balance tests (side
      by-side, semi-tandem and tandem test with eyes open and -closed), four-meter walk
      test, timed up and go test, chair stand test, handgrip strength and two
      subjective questions on mobility. Direct segmental multi-frequency bioelectrical
      impedance analysis was used to measure muscle mass. Five commonly used
      definitions of sarcopenia were applied. Diagnostic accuracy was determined by
      sensitivity, specificity and area under the curve. RESULTS: Physical performance
      measures, i.e. side-by-side test, tandem test, chair stand test and handgrip
      strength, were associated with at least one definition of sarcopenia. Diagnostic
      accuracy of these physical performance measures was poor. CONCLUSIONS: Single
      physical performance measures could not identify older individuals with
      sarcopenia, according to five different definitions of sarcopenia.

PMID- 30298178
TI  - What We Learn from the CTAD (Clinical Trials Alzheimer's Disease) 2018.

PMID- 30298179
TI  - Assessment of Instrumental Activities of Daily Living in Older Adults with
      Subjective Cognitive Decline Using the Virtual Reality Functional Capacity
      Assessment Tool (VRFCAT).
AB  - BACKGROUND: Continuing advances in the understanding of Alzheimer's disease
      progression have inspired development of disease-modifying therapeutics intended
      for use in preclinical populations. However, identification of clinically
      meaningful cognitive and functional outcomes for individuals who are, by
      definition, asymptomatic remains a significant challenge. Clinical trials for
      prevention and early intervention require measures with increased sensitivity to
      subtle deficits in instrumental activities of daily living (IADL) that comprise
      the first functional declines in prodromal disease. Validation of potential
      endpoints is required to ensure measure sensitivity and reliability in the
      populations of interest. OBJECTIVES: The present research validates use of the
      Virtual Reality Functional Capacity Assessment Tool (VRFCAT) for performance
      based assessment of IADL functioning in older adults (age 55+) with subjective
      cognitive decline. DESIGN: Cross-sectional validation study. SETTING: All
      participants were evaluated on-site at NeuroCog Trials, Durham, NC, USA.
      PARTICIPANTS: Participants included 245 healthy younger adults ages 20-54 (131
      female), 247 healthy older adults ages 55-91 (151 female) and 61 older adults
      with subjective cognitive decline (SCD) ages 56-97 (45 female). MEASURES: Virtual
      Reality Functional Capacity Assessment Tool; Brief Assessment of Cognition App;
      Alzheimer's Disease Cooperative Study Prevention Instrument Project - Mail-In
      Cognitive Function Screening Instrument; Alzheimer's Disease Cooperative Study
      Instrumental Activities of Daily Living - Prevention Instrument, University of
      California, San Diego Performance-Based Skills Assessment - Validation of
      Intermediate Measures; Montreal Cognitive Assessment; Trail Making Test- Part B.
      RESULTS: Participants with SCD performed significantly worse than age-matched
      normative controls on all VRFCAT endpoints, including total completion time,
      errors and forced progressions (p<=0001 for all, after Bonferonni correction).
      Consistent with prior findings, both groups performed significantly worse than
      healthy younger adults (age 20-54). Participants with SCD also performed
      significantly worse than controls on objective cognitive measures. VRFCAT
      performance was strongly correlated with cognitive performance. In the SCD group,
      VRFCAT performance was strongly correlated with cognitive performance across
      nearly all tests with significant correlation coefficients ranging from 0.3 to
      0.7; VRFCAT summary measures all had correlations greater than r=0.5 with MoCA
      performance and BAC App Verbal Memory (p<0.01 for all). CONCLUSIONS: Findings
      suggest the VRFCAT provides a sensitive tool for evaluation of IADL functioning
      in individuals with subjective cognitive decline. Strong correlations with
      cognition across groups suggest the VRFCAT may be uniquely suited for clinical
      trials in preclinical AD, as well as longitudinal investigations of the
      relationship between cognition and function.

PMID- 30298181
TI  - Geographic Clusters of Alzheimer's Disease Mortality Rates in the USA: 2008-2012.
AB  - IMPORTANCE: The results identified geographic clusters of high and low
      Alzheimer's disease (AD)-related mortality across the contiguous United States.
      These clusters identify specific geographic groupings of counties that allow
      researchers to narrow the focus to identify some of the biopsychosocial variables
      contributing to increased or decreased AD mortality. OBJECTIVES: To determine the
      extent to which geographic clusters exist where AD mortality significantly
      differs from the national average. Such knowledge could further future research
      in a more focused study of variables that are contributing to these differences.
      DESIGN: Age adjusted AD mortality rates were analyzed with a spatial cluster
      analysis using the disease surveillance software SatScanTM. RESULTS: Three large
      clusters had elevated age-adjusted AD mortality of at least 60% above the
      national average. These clusters were in Washington State, Iowa, and North and
      South Dakota. Below average AD mortality was observed in several areas including
      New York City, and parts of Arizona, California, Arkansas and Texas. Conclusion
      and Relevance: This study demonstrates the use of disease surveillance
      methodology in identifying geographic patterns of unusually high or low AD
      mortality rates in the USA. Such results provide supporting evidence of
      appropriate locations to test interventions with the goal to reduce AD mortality.

PMID- 30298180
TI  - Female Sex and Alzheimer's Risk: The Menopause Connection.
AB  - Along with advanced age and apolipoprotein E (APOE)-4 genotype, female sex is a
      major risk factor for developing late-onset Alzheimer's disease (AD). Considering
      that AD pathology begins decades prior to clinical symptoms, the higher risk in
      women cannot simply be accounted for by their greater longevity as compared to
      men. Recent investigation into sex-specific pathophysiological mechanisms behind
      AD risk has implicated the menopause transition (MT), a midlife neuroendocrine
      transition state unique to females. Commonly characterized as ending in
      reproductive senescence, many symptoms of MT are neurological, including
      disruption of estrogen-regulated systems such as thermoregulation, sleep, and
      circadian rhythms, as well as depression and impairment in multiple cognitive
      domains. Preclinical studies have shown that, during MT, the estrogen network
      uncouples from the brain bioenergetic system. The resulting hypometabolic state
      could serve as the substrate for neurological dysfunction. Indeed, translational
      brain imaging studies demonstrate that 40-60 year-old perimenopausal and
      postmenopausal women exhibit an AD-endophenotype characterized by decreased
      metabolic activity and increased brain amyloid-beta deposition as compared to
      premenopausal women and to age-matched men. This review discusses the MT as a
      window of opportunity for therapeutic interventions to compensate for brain
      bioenergetic crisis and combat the subsequent increased risk for AD in women.

PMID- 30298182
TI  - Psychometric Evaluation of the Neuropsychological Test Battery in Individuals
      with Normal Cognition, Mild Cognitive Impairment, or Mild to Moderate Alzheimer's
      Disease: Results from a Longitudinal Study.
AB  - BACKGROUND: The Neuropsychological Test Battery (NTB) is a combination of widely
      used clinical neuropsychological tests measuring memory and executive function
      and was designed to overcome some of the limitations of the traditionally used
      Alzheimer's disease Assessment Scale - Cognitive subscale (ADAS-Cog). A
      previously reported account indicated high levels of NTB reliability in patients
      with mild-to-moderate Alzheimer's disease (AD) and mild cognitive impairment
      (MCI). OBJECTIVES: We examined capacity of the Neuropsychological Test Battery
      (NTB) and its component subtests to measure cognitive change over time.
      Correlations with other cognitive and functional assessments were also
      determined. Design, Settings, Participants: This was a multicentre, prospective,
      non-interventional, longitudinal cohort study involving patients with mild-to
      moderate AD (n=196), MCI (n=70), or cognitively normal control participants (NC,
      n=75). INTERVENTION: The NTB, as well as other Clinical Outcome Assessments
      including, ADAS-Cog, other cognitive measures, functional/behavioral
      questionnaires, health outcome questionnaires, and resource utilization tools
      were administered. RESULTS: Mean change from baseline for the NTB composite score
      and the six individual NTB subtests showed greater reductions in performance over
      time in the AD and MCI groups, compared with NC group. The ADAS-Cog was found to
      be more sensitive to change than the NTB in all three populations. CONCLUSIONS:
      The NTB showed high correlation with the ADAS-Cog and appears to be a sensitive
      and reliable assessment tool for measuring cognitive decline in patients with
      mild-to-moderate AD. However, the ADAS-Cog was found to be more sensitive to
      change over time in both the AD and MCI populations.

PMID- 30298184
TI  - Pimavanserin: Potential Treatment For Dementia-Related Psychosis.
AB  - Psychosis is common across dementia types with a prevalence of 20% to 70%.
      Currently, no pharmacologic treatment is approved for dementia-related psychosis.
      Atypical antipsychotics are frequently used to treat these disorders, despite
      significant safety concerns. Pimavanserin, a selective 5-HT2A inverse
      agonist/antagonist, was approved in the U.S. for treating hallucinations and
      delusions associated with Parkinson's disease psychosis (PDP). Patients in the
      pimavanserin group experienced a significant (p=0.001) improvement in Scale for
      the Assessment of Positive Symptoms - Parkinson's disease (SAPS-PD) scores vs.
      placebo. In a subgroup analysis of patients with cognitive impairment (MMSE score
      >=21 but <=24), the observed improvement on the SAPS-PD with pimavanserin (N=50)
      was also significant (p=0.002) and larger than in the overall study population
      without an adverse effect on cognition. In a Phase 2 study with pimavanserin in
      Alzheimer's disease psychosis, pimavanserin significantly (p=0.045) improved
      psychosis at Week 6 vs. placebo on the NPI-NH Psychosis Score (PS). In a
      prespecified subgroup of patients with a baseline NPI-NH PS >=12, a substantively
      larger treatment effect (p=0.011) was observed vs. participants with NPI-NH PS
      <12. The results of these studies in cognitively impaired patients with PDP
      provided the scientific foundation for an ongoing study of pimavanserin for
      treating patients with dementia-related psychosis associated with the most common
      neurodegenerative disorders. The study uses a relapse-prevention design with the
      endpoint of time-to-relapse of psychosis to evaluate the long-term efficacy and
      safety of pimavanserin as a potential treatment for hallucinations and delusions
      of dementia-related psychosis.

PMID- 30298185
TI  - Letter to the Editor: Preventing Dementia through Community Involvement and
      Altruistic Behaviors.

PMID- 30298183
TI  - Clinical Application of APOE in Alzheimer's Prevention: A Precision Medicine
      Approach.
AB  - Population-attributable risk models estimate that up to one-third of Alzheimer's
      disease (AD) cases may be preventable through risk factor modification. The field
      of AD prevention has largely focused on addressing these factors through
      universal risk reduction strategies for the general population. However,
      targeting these strategies in a clinical precision medicine fashion, including
      the use of genetic risk factors, allows for potentially greater impact on AD risk
      reduction. Apolipoprotein E (APOE), and specifically the APOE epsilon4 variant,
      is one of the most well-established genetic influencers on late-onset AD risk. In
      this review, we evaluate the impact of APOE epsilon4 carrier status on AD
      prevention interventions, including lifestyle, nutrigenomic, pharmacogenomic, AD
      comorbidities, and other biological and behavioral considerations. Using a
      clinical precision medicine strategy that incorporates APOE epsilon4 carrier
      status may provide a highly targeted and distinct approach to AD prevention with
      greater potential for success.

PMID- 30298187
TI  - Supplement: 11th Conference Clinical Trials Alzheimer's Disease, October 24-27,
      2018, Barcelona, Spain, Posters - Late Breaking News.

PMID- 30298186
TI  - Supplement: 11th Conference Clinical Trials Alzheimer's Disease, October 24-27,
      2018, Barcelona, Spain, Symposia - Oral Communications - Late Breaking News.

PMID- 30298188
TI  - Altered brain functional network in children with type 1 Gaucher disease: a
      longitudinal graph theory-based study.
AB  - PURPOSE: Previous studies have investigated the brain structural abnormalities in
      children with type I Gaucher disease (GD). The purpose of our study is to
      investigate the topological efficiency of the brain functional network in
      children with type 1 GD. METHODS: Twenty-two children diagnosed with type 1 GD
      and 22 sex- and age-matched healthy controls (HCs) underwent resting-state
      functional MRI (rs-fMRI) examination. For longitudinal study, the GD patients
      underwent rs-fMRI examination again after 4.6 years. Graph theoretical analysis
      was used to assess the brain network topological properties at the global and
      regional levels. RESULTS: Compared with the HCs, the children with type 1 GD
      showed a decreased efficiency in functional segregation with a decreased gamma
      (normalized clustering coefficient). In addition, the balance between functional
      segregation and integration was disrupted with decreased small-worldness (sigma).
      At the regional level, the children with type 1 GD showed significantly decreased
      nodal degree and efficiency in the right precentral gyrus (PreCG.R) and left
      postcentral gyrus (PoCG.L). The significantly altered gamma, sigma, and nodal
      degree in the PreCG.R and PoCG.L were negatively correlated with the disease
      duration. No significant alterations in the global and regional topological
      properties were identified in these patients over time. CONCLUSION: Compared with
      that of the HCs, the efficiency of the brain functional network in the children
      with type 1 GD was disrupted, and regional involvement was located in motor- and
      sensory-related regions. The efficiency of the brain functional network in these
      patients remained stable over time.

PMID- 30298189
TI  - [Importance of self-assessment in functional evaluation of trauma patients].
AB  - The principle of self-assessment is performed successfully in a wide variety of
      medical disciplines and is increasingly gaining importance in orthopedic trauma
      surgery. Through the development and validation of joint-specific self-assessment
      questionnaires that enable estimation of the range of motion, a large number of
      patient-based instruments are available for comprehensive follow-up examination.
      A recently performed proof of concept study showed a high patient acceptance and
      therefore the development of a prospective, patient-centered fracture register
      based on the self-assessment functional analysis seems to be promising. The data
      obtained should reflect not only the reality of fracture treatment but also
      generate valuable epidemiological data with which evidence-based guidelines can
      be formed.

PMID- 30298190
TI  - [Transcription factors in tumor diagnosis].
AB  - Transcription factors are a heterogeneous group of DNA-binding proteins that
      regulate the transcription of distinct genes. Due to their cell-type specificity
      and cell lineage restriction, numerous transcription factors have been
      established in recent years as excellent, sensitive, and specific
      immunohistochemical tumor markers. As compared to other cytoplasmic and
      membranous differentiation markers, the nuclear immunolocalization of
      transcription factors is often more stably preserved. Therefore, cell lineage
      specific transcription factors can be detected even in poorly differentiated
      metastatic tumors. However, for their reliable diagnostic use, detailed knowledge
      is required on their expression profiles, which are often more complex than
      initially assumed.CDX2 is a sensitive marker for colorectal adenocarcinomas but
      is also expressed in upper abdominal adenocarcinomas, mucinous carcinomas of lung
      and ovary, and midgut neuroendocrine tumors. A higher degree of specificity for
      colorectal origin is provided by SATB2. TTF-1 is a valuable marker particularly
      for pulmonary adenocarcinomas, but may also be focally expressed "aberrantly" in
      abdominal and gynecological adenocarcinomas. GATA3 is found in breast and
      urothelial carcinomas but also in squamous cell carcinomas. PAX8 is a highly
      sensitive marker of all subtypes of gynecological adenocarcinomas, renal cell
      carcinomas, and thyroid carcinomas. Further transcription factors characterized
      by molecular biology have meanwhile become diagnostically relevant, the number of
      which is increasing.Principally, for the diagnostic use of transcription factors
      as immunohistochemical tumor markers, clinical and radiological data as well as
      conventional histopathology should always be carefully considered and if
      necessary they should be applied in the context of a marker panel.

PMID- 30298191
TI  - TRPC channels in exercise-mimetic therapy.
AB  - Physical exercise yields beneficial effects on all types of muscle cells, which
      are essential for the maintenance of cardiovascular homeostasis and good blood
      circulation. Daily moderate exercise increases systemic antioxidative capacity,
      which can lead to the prevention of the onset and progression of oxidative stress
      related diseases. Therefore, exercise is now widely accepted as one of the best
      therapeutic strategies for the treatment of ischemic (hypoxic) diseases.
      Canonical transient receptor potential (TRPC) proteins are non-selective cation
      channels activated by mechanical stress and/or stimulation of phospholipase C
      coupled surface receptors. TRPC channels, especially diacylglycerol-activated
      TRPC channels (TRPC3 and TRPC6; TRPC3/6), play a key role in the development of
      cardiovascular remodeling. We have recently found that physical interaction
      between TRPC3 and NADPH oxidase (Nox) 2 under hypoxic stress promotes Nox2
      dependent reactive oxygen species (ROS) production and mediates rodent cardiac
      plasticity, and inhibition of the TRPC3-Nox2 protein complex results in
      enhancement of myocardial compliance and flexibility similar to that observed in
      exercise-treated hearts. In this review, we describe current understanding of the
      roles of TRPC channels in striated muscle (patho)physiology and propose that
      targeting TRPC-based protein complexes could be a new strategy to imitate
      exercise therapy.

PMID- 30298192
TI  - Balancing metabolome coverage and reproducibility for untargeted NMR-based
      metabolic profiling in tissue samples through mixture design methods.
AB  - Untargeted metabolomics attempts to acquire a comprehensive and reproducible set
      of small-molecule metabolites in biological systems. However, metabolite
      extraction method significantly affects the quality of metabolomics data. In the
      present study, we calculated the number of peaks (NP) and coefficient of
      variation (CV) to reflect metabolome coverage and reproducibility in untargeted
      NMR-based metabolic profiling of tissue samples in rats under different
      methanol/chloroform/water (MCW) extraction conditions. Different MCW extractions
      expectedly generated diverse characteristics of metabolome. Moreover, the classic
      MCW method revealed tissue-specific differences in the NP and CV values. To
      obtain high-quality metabolomics data, therefore, we used mixture design methods
      to optimize the MCW extraction strategy by maximizing the NP value and minimizing
      the CV value in each tissue sample. Results show that the optimal formulations of
      MCW extraction were 2:2:8 (ml/mg tissue) for brain sample, 2:4:6 (ml/mg tissue)
      for heart sample, 1.3:2:8.7 (ml/mg tissue) for liver sample, 4:2:6 (ml/mg tissue)
      for kidney sample, 2:3:7 (ml/mg tissue) for muscle sample, and 2:4:6 (ml/mg
      tissue) for pancreas sample. Therefore, these findings demonstrate that different
      tissue samples need a specific optimal extraction condition for balancing
      metabolome coverage and reproducibility in the untargeted metabolomics study.
      Mixture design method is an effective tool to optimize metabolite extraction
      strategy for tissue samples. Graphical abstract ?.

PMID- 30298193
TI  - Disposable amperometric immunosensor for Saccharomyces cerevisiae based on
      carboxylated graphene oxide-modified electrodes.
AB  - A sensitive and disposable amperometric immunosensor for Saccharomyces cerevisiae
      was constructed by using carbon screen-printed electrodes modified with propionic
      acid-functionalized graphene oxide as transduction element. The affinity-based
      biosensing interface was assembled by covalent immobilization of a specific
      polyclonal antibody on the carboxylate-enriched electrode surface via a water
      soluble carbodiimide/N-hydroxysuccinimide coupling approach. A concanavalin A
      peroxidase conjugate was further used as signaling element. The immunosensor
      allowed the amperometric detection of the yeast in buffer solution and white wine
      samples in the range of 10-107 CFU/mL. This electroanalytical device also
      exhibited low detection limit and high selectivity, reproducibility, and storage
      stability. The immunosensor was successfully validated in spiked white wine
      samples.

PMID- 30298194
TI  - ABC Spotlight on magnetic composite nanoparticles in analysis: increased
      sensitivity at decreased analysis time.

PMID- 30298196
TI  - Correction to: 3D SASHA myocardial T1 mapping with high accuracy and improved
      precision.
AB  - The original version of this article unfortunately contained a mistake. The
      presentation of Equation was incorrect. The corrected equation is given below.

PMID- 30298197
TI  - A Nonlinear Mathematical Model of Drug Delivery from Polymeric Matrix.
AB  - The objective of the present study is to mathematically model the integrated
      kinetics of drug release in a polymeric matrix and its ensuing drug transport to
      the encompassing biological tissue. The model embodies drug diffusion,
      dissolution, solubilization, polymer degradation and
      dissociation/recrystallization phenomena in the polymeric matrix accompanied by
      diffusion, advection, reaction, internalization and specific/nonspecific binding
      in the biological tissue. The model is formulated through a system of nonlinear
      partial differential equations which are solved numerically in association with
      pertinent set of initial, interface and boundary conditions using suitable finite
      difference scheme. After spatial discretization, the system of nonlinear partial
      differential equations is reduced to a system of nonlinear ordinary differential
      equations which is subsequently solved by the fourth-order Runge-Kutta method.
      The model simulations deal with the comparison between a drug delivery from a
      biodegradable polymeric matrix and that from a biodurable polymeric matrix.
      Furthermore, simulated results are compared with corresponding existing
      experimental data to manifest the efficaciousness of the advocated model. A
      quantitative analysis is performed through numerical computation relied on model
      parameter values. The numerical results obtained reveal an estimate of the
      effects of biodegradable and biodurable polymeric matrices on drug release rates.
      Furthermore, through graphical representations, the sensitized impact of the
      model parameters on the drug kinetics is illustrated so as to assess the model
      parameters of significance.

PMID- 30298195
TI  - The clinical features and outcome of scan-negative and scan-positive cases in
      suspected cauda equina syndrome: a retrospective study of 276 patients.
AB  - BACKGROUND: The majority of patients presenting with suspected clinical cauda
      equina syndrome (CES) have no identifiable structural cause for their symptoms
      ('scan-negative' CES). Understanding these patients aids clinical differentiation
      and management in CES. METHODS: A retrospective electronic note review was
      undertaken of patients presenting with suspected CES, defined as >= 1 of acute
      bladder, bowel, sexual dysfunction or saddle numbness, to a regional
      neurosciences centre. We investigated radiology, clinical features, psychiatric
      and functional disorder comorbidities and outcome of patients with 'scan
      negative' CES and patients with MRI confirmed compression of the cauda equina
      ('scan-positive' CES). RESULTS: 276 patients were seen over 16 months. There were
      three main radiologically defined patient groups: (1) 'scan-positive' CES (n =
      78, mean age 48 years, 56% female), (2) 'scan-negative' CES without central canal
      stenosis but with lumbosacral nerve root compression not explaining the clinical
      presentation (n = 87, mean age 43 years, 68% female) and (3) 'scan-negative' CES
      without neural compromise (n = 104, mean age 42 years, 70% female). In the two
      'scan-negative' groups (no neural compromise and nerve root compression), there
      were higher rates of functional disorders (37% and 29% vs. 9%), functional
      neurological disorders (12% and 11% vs 0%) and psychiatric comorbidity (53% and
      40% vs 20%). On follow-up (mean 13-16 months), only 1 of the 191 patients with
      'scan-negative' CES was diagnosed with an explanatory neurological disorder
      (transverse myelitis). CONCLUSIONS: The data support a model in which scan
      negative cauda equina syndrome arises as an end pathway of acute pain, sometimes
      with partly structural findings and vulnerability to functional disorders.

PMID- 30298198
TI  - Stochastic Dynamics of the Latently Infected Cell Reservoir During HIV Infection.
AB  - The presence of cells latently infected with HIV is currently considered to be a
      major barrier to viral eradication within a patient. Here, we consider birth
      death-immigration models for the latent cell population in a single patient, and
      present analytical results for the size of this population in the absence of
      treatment. We provide results both at steady state (viral set point), and during
      the non-equilibrium setting of early infection. We obtain semi-analytic results
      showing how latency-reversing drugs might be expected to affect the size of the
      latent pool over time. We also analyze the probability of rare mutant viral
      strains joining the latent cell population, allowing for steady-state and dynamic
      viral populations within the host.

PMID- 30298199
TI  - Ureteral stents for malignant extrinsic ureteral obstruction: outcomes and
      factors predicting stent failure.
AB  - BACKGROUND: This study investigated the clinical outcomes of stent placement for
      malignant extrinsic ureteral obstruction (MUO) and predictive factors for stent
      failure. METHODS: We retrospectively analyzed clinical data for 91 patients with
      radiologically significant hydronephrosis due to MUO who underwent successful
      stent placement. In total, 132 ureters were stented for the decompression.
      Factors related to stent failure were analyzed with a Cox proportional hazards
      model. RESULTS: Stent failure occurred in 25 ureters in 20 patients. The median
      interval to failure was 63 days. The multivariate analysis showed that the
      significant predictors of stent failure were bladder invasion and severe
      hydronephrosis before the stent insertion. The patients were divided into three
      groups based on these two factors: low-risk (neither factor; 85 patients),
      intermediate-risk (one factor; 37), and high-risk (both factors; 10). The median
      stent failure-free survival rate at 3 months was 94.8% in the low-risk, 71.8% in
      the intermediate-risk and 55.6% in the high-risk group, respectively. Of the
      ureters with stent failure, there was successful re-replacement of internal
      stents in 3 low-risk, 6 intermediate-risk and no high-risk ureters. Replacement
      by nephrostomy was done in 2 low-risk, 5 intermediate-risk and 7 high-risk
      ureters. CONCLUSION: The patients considered at low-risk could be managed without
      stent failure by internal stenting. However, the patients at high-risk may
      require the consideration of nephrostomy or other alternatives as the initial
      treatment. Our stratification model may allow better risk stratification for
      patients with regard to ureteral stenting, helping to identify patients for whom
      ureteral stenting is indicated.

PMID- 30298200
TI  - Transmission of cotton leaf curl disease: answer to a long-standing question.
AB  - Cotton leaf curl disease (CLCuD) has been a major constraint to cotton production
      across Pakistan and northwestern India since the early 1990s. The disease is
      caused by a number of begomoviruses, including Cotton leaf curl Multan virus
      (CLCuMuV), which associate with a specific host range and symptom determining
      betasatellite known as Cotton leaf curl Multan betasatellite (CLCuMuB). Bemisia
      tabaci is a complex of cryptic species that consists of numerous (> 44)
      morphologically indistinguishable and, at least partially, reproductively
      isolated species. CLCuD has recently been introduced into parts of China but has
      not, at least so far, become a problem in the major cotton regions. The disease
      in China has been shown to be caused by CLCuMuV with CLCuMuB, which is believed
      to have been introduced from South Asia in ornamental plants. To understand the
      basis for this lack of spread of CLCuD into the cotton-growing areas of China,
      Pan et al. (Phytopathology 108:1172-1183, 2018) investigated the transmission of
      CLCuMuV/CLCuMuB by B. tabaci. The study showed that, of the four cryptic B.
      tabaci species investigated, only the cryptic species Asia II 1 was able to
      efficiently transmit CLCuMuV/CLCuMuB. Significantly, Asia II 1 is not present in
      the major cotton-growing regions of China. The results of Pan et al.
      (Phytopathology 108:1172-1183, 2018) are discussed with particular emphasis on
      the situation of CLCuD in Pakistan and northwestern India, which differs
      significantly from the situation in China.

PMID- 30298202
TI  - Similar neurocognitive outcomes after 48 weeks in HIV-1-infected participants
      randomized to continue tenofovir/emtricitabine + atazanavir/ritonavir or simplify
      to abacavir/lamivudine + atazanavir.
AB  - Human immunodeficiency virus (HIV)-associated neurocognitive disorders can
      persist in many patients despite achieving viral suppression while on
      antiretroviral therapy (ART). Neurocognitive function over 48 weeks was evaluated
      using a Cogstate test battery assessing psychomotor function, attention,
      learning, and working memory in 293 HIV-1-infected, ART-experienced, and
      virologically suppressed adults. The ASSURE study randomized participants 1:2 to
      remain on tenofovir/emtricitabine (TDF/FTC) and ritonavir-boosted atazanavir
      (ATV/r) or simplify to abacavir/lamivudine + atazanavir (ABC/3TC + ATV).
      Neurocognitive z-scores were computed using demographically adjusted normative
      data and were classified as "impaired" (defined as either a z-score <= - 2 or
      having 2 or more standardized individual test z-scores <= - 1); while higher
      scores (equaling better performance) were classified as "normal". By z-scores,
      54.7% of participants had impaired neurocognition at baseline and 50.2% at week
      48. There were no significant differences (p < 0.05) in the baseline-adjusted
      performance between treatment groups for any individual test or by z-score.
      Specific demographic and medical risk factors were evaluated by univariate
      analysis for impact on neurocognitive performance. Factors with p < 0.10 were
      evaluated by backwards regression analysis to identify neurocognition-correlated
      factors after accounting for treatment, assessment, and baseline. Four risk
      factors at baseline for impaired neurocognition were initially identified: lower
      CD4 nadir lymphocyte counts, higher Framingham risk scores, and interleukin-6
      levels, and a history of psychiatric disorder not otherwise specified, however
      none were found to moderate the effect of treatment on neurocognition. In this
      aviremic, treatment-experienced population, baseline-adjusted neurocognitive
      function remained stable and equivalent over 48 weeks with both TDF/FTC + ATV/r
      treated and in the ART-simplified ABC/3TC + ATV treatment groups.

PMID- 30298203
TI  - Effects of age, HIV, and HIV-associated clinical factors on neuropsychological
      functioning and brain regional volume in HIV+ patients on effective treatment.
AB  - It is yet unclear if people infected with human immunodeficiency virus (HIV+) on
      stable, combined antiretroviral therapies (cARTs) decline with age at the same or
      greater rate than healthy people. In this study, we examined independent and
      interactive effects of HIV, age, and HIV-related clinical parameters on
      neuropsychological functioning and brain regional volume in a sizable group of
      Polish HIV+ men receiving cART. We also estimated the impact of nadir CD4 cell
      count, CD4 cell count during participation in the study, duration of HIV
      infection, or duration of cART along with age. Ninety-one HIV+ and 95 control
      (HIV-) volunteers ages 23-75 completed a battery of neuropsychological tests, and
      54 HIV+ and 62 HIV- of these volunteers participated in a brain imaging
      assessment. Regional brain volume in the cortical and subcortical regions was
      measured using voxel-based morphometry. We have found that HIV and older age were
      independently related to lower attention, working memory, nonverbal fluency, and
      visuomotor dexterity. Older age but not HIV was associated with less volume in
      several cortical and subcortical brain regions. In the oldest HIV+ participants,
      age had a moderating effect on the relationship between the duration of cART and
      visuomotor performance, such as that older age decreased speed of visuomotor
      performance along with every year on cART. Such results may reflect the efficacy
      of cART in preventing HIV-associated brain damage. They also highlight the
      importance of monitoring neuropsychological functioning and brain structure in
      HIV+ patients. This is particularly important in older patients with long
      adherence to cART.

PMID- 30298204
TI  - Fate of manuscripts rejected by Intensive Care Medicine from 2013 to 2016: a
      follow-up analysis.

PMID- 30298201
TI  - Functional MRI and delay discounting in patients infected with hepatitis C.
AB  - Hepatitis C virus-infected (HCV+) adults evidence increased rates of psychiatric
      and cognitive difficulties. This is the first study to use functional magnetic
      resonance imaging (fMRI) to examine brain activation in untreated HCV+ adults. To
      determine whether, relative to non-infected controls (CTLs), HCV+ adults exhibit
      differences in brain activation during a delay discounting task (DDT), a measure
      of one's tendency to choose smaller immediate rewards over larger delayed rewards
      one aspect of impulsivity. Twenty adults with HCV and 26 CTLs completed an fMRI
      protocol during the DDT. Mixed effects regression analyses of hard versus easy
      trials of the DDT showed that, compared with CTLs, the HCV+ group exhibited less
      activation in the left lateral occipital gyrus, precuneus, and superior frontal
      gyrus. There were also significant interactive effects for hard-easy contrasts in
      the bilateral medial frontal gyrus, left insula, left precuneus, left inferior
      parietal lobule, and right temporal occipital gyrus; the CTL group evidenced a
      positive relationship between impulsivity and activation, while the HCV+ group
      exhibited a negative relationship. Within the HCV+ group, those with high viral
      load chose immediate rewards more often than those with low viral load,
      regardless of choice difficulty; those with low viral load chose immediate
      rewards more often on hard choices relative to easy choices. Results show that
      HCV+ patients exhibit greater impulsive behavior when presented with difficult
      choices, and impulsivity is negatively related to activation in regions important
      for cognitive control. Thus, interventions that decrease impulsive choice may be
      warranted with some HCV+ patients.

PMID- 30298205
TI  - Rouhier's colpocleisis with concomitant vaginal hysterectomy: an instructive
      video for female pelvic surgeons.
AB  - INTRODUCTION AND HYPOTHESIS: The treatment of pelvic organ prolapse (POP) in
      elderly women can be challenging. The vaginal operation known as colpocleisis,
      the total occlusion of the urogenital hiatus, with concomitant hysterectomy was
      described by Rouhier and represents a safe, time-saving, and reproducible
      procedure in the case of POP associated with uterine pathological conditions. It
      is suitable for elderly women who do not require preservation of coital function.
      The objective of this video is to provide anatomical illustrations and a precise
      description of the surgical steps. METHODS: We present the case of a 62-year-old
      woman who was referred for hysterectomy in the context of metastatic endometrial
      cancer. She complained about vaginal bulge and was diagnosed with a POP-Q stage 4
      genital prolapse on physical examination. Due to important comorbidities such as
      arterial hypertension, obesity, and three-site metastatic disease, we suggested a
      colpocleisis with concomitant vaginal hysterectomy. This approach was intended to
      treat the prolapse and perform a palliative surgery to alleviate abnormal uterine
      bleeding. RESULTS: This video illustrates the different surgical steps of a
      colpohysterectomy according to Rouhier. No intraoperative complications occurred
      and the postoperative follow-up was uneventful. The patient was fully satisfied
      and POP has not recurred after a 17-month follow-up. CONCLUSIONS: Colpocleisis
      should remain an exceptional approach, but could be offered to sexually inactive
      women of advanced age after thorough discussion and patient consent. If a
      hysterectomy is necessary, Rouhier's operation offers a time-saving,
      reproducible, and efficient option for women with symptomatic POP who do not
      desire future vaginal intercourse.

PMID- 30298206
TI  - Rectal mesh erosion after posterior vaginal kit repair.
AB  - INTRODUCTION AND HYPOTHESIS: The present video shows a rare case of erosion
      through the full rectal wall into the rectum after a transperineal implant of a
      double-arm polypropylene kit. METHODS: A 70-year-old woman underwent a
      transperineal implant of a double-arm polypropylene kit. One year after surgery,
      she developed bothersome symptoms in the posterior perineum including heaviness,
      pain and rectal bleeding during defecation. A clinical examination showed the
      presence of a part of the prothesis traversing the rectal cavity. A minimally
      invasive transanal approach was performed to remove the mesh and restore the
      rectal integrity. RESULTS: This surgical technique demonstrates rectal mesh
      removal with a transanal approach. CONCLUSIONS: To our knowledge, this is a rare
      complication of rectal erosion of a posterior transperineal mesh kit. The aim of
      this video is to show a complete transanal approach to treating this serious
      complication avoiding the more invasive and traumatic abdominal procedure.

PMID- 30298207
TI  - Choline and choline-related nutrients in regular and preterm infant growth.
AB  - BACKGROUND: Choline is an essential nutrient, with increased requirements during
      development. It forms the headgroup of phosphatidylcholine and sphingomyelin in
      all membranes and many secretions. Phosphatidylcholine is linked to cell
      signaling as a phosphocholine donor to synthesize sphingomyelin from ceramide, a
      trigger of apoptosis, and is the major carrier of arachidonic and docosahexaenoic
      acid in plasma. Acetylcholine is important for neurodevelopment and the placental
      storage form for fetal choline supply. Betaine, a choline metabolite, functions
      as osmolyte and methyl donor. Their concentrations are all tightly regulated in
      tissues. CLINCAL IMPACT: During the fetal growth spurt at 24-34-week
      postmenstrual age, plasma choline is higher than beyond 34 weeks, and threefold
      higher than in pregnant women [45 (36-60) umol/L vs. 14 (10-17) umol/L]. The
      rapid decrease in plasma choline after premature birth suggests an untimely
      reduction in choline supply, as cellular uptake is proportional to plasma
      concentration. Supply via breast milk, with phosphocholine and alpha
      glycerophosphocholine as its major choline components, does not prevent such
      postnatal decrease. Moreover, high amounts of liver PC are secreted via bile,
      causing rapid hepatic choline turnover via the enterohepatic cycle, and
      deficiency in case of pancreatic phospholipase A2 deficiency or intestinal
      resection. Choline deficiency causes hepatic damage and choline accretion at the
      expense of the lungs and other tissues. CONCLUSION: Choline deficiency may
      contribute to the impaired lean body mass growth and pulmonary and neurocognitive
      development of preterm infants despite adequate macronutrient supply and weight
      gain. In this context, a reconsideration of current recommendations for choline
      supply to preterm infants is required.

PMID- 30298208
TI  - The Yin-Yang of CYP3A4: a Bayesian meta-analysis to quantify inhibition and
      induction of CYP3A4 metabolism in humans and refine uncertainty factors for
      mixture risk assessment.
AB  - Quantifying differences in pharmacokinetics (PK) and toxicokinetics (TK) provides
      a science-based approach to refine uncertainty factors (UFs) for chemical risk
      assessment. Cytochrome P450 (CYP) 3A4-the major hepatic and intestinal human CYP
      and the P-glycoprotein (Pgp) transporter share a vast range of common substrates
      for which PK may be modulated through inhibition or induction in the presence of
      grapefruit juice (GFJ) or St. John's wort (SJW), respectively. Here, an extensive
      literature search was performed on PK interactions for CYP3A4 and Pgp substrates
      after oral co-exposure to GFJ and SJW. Relevant data from 109 publications,
      extracted for both markers of acute (Cmax) and chronic [clearance and area under
      the plasma concentration-time curve (AUC)] exposure, were computed into a
      Bayesian hierarchical meta-analysis model. Bioavailability (F) and substrate
      fraction metabolised by CYP3A4 (Fm) were identified as the variables exhibiting
      the highest impact on the magnitude of interaction. The Bayesian meta-regression
      model developed provided good predictions for magnitudes of inhibition (maximum
      5.3-fold with GFJ) and induction (maximum 2.3-fold with SJW). Integration of
      CYP3A4 variability, F, Fm and magnitude of interaction provided the basis to
      derive a range of CYP3A4 and Pgp-related UFs. Such CYP3A4 and Pgp-related UFs can
      be derived in the absence of human data using in vitro TK evidence for CYP3A4/Pgp
      inhibition or induction as conservative in silico options. The future development
      of quantitative in vitro-in vivo extrapolation models for mixture risk assessment
      is discussed with particular attention to integrating human in vitro and in vivo
      P/TK data on interactions with pathway-related variability.

PMID- 30298209
TI  - Major changes of cell function and toxicant sensitivity in cultured cells
      undergoing mild, quasi-natural genetic drift.
AB  - Genomic drift affects the functional properties of cell lines, and the
      reproducibility of data from in vitro studies. While chromosomal aberrations and
      mutations in single pivotal genes are well explored, little is known about
      effects of minor, possibly pleiotropic, genome changes. We addressed this
      question for the human dopaminergic neuronal precursor cell line LUHMES by
      comparing two subpopulations (SP) maintained either at the American-Type-Culture
      Collection (ATCC) or by the original provider (UKN). Drastic differences in
      susceptibility towards the specific dopaminergic toxicant 1-methyl-4
      phenylpyridinium (MPP+) were observed. Whole-genome sequencing was performed to
      identify underlying genetic differences. While both SP had normal chromosome
      structures, they displayed about 70 differences on the level of amino acid
      changing events. Some of these differences were confirmed biochemically, but none
      offered a direct explanation for the altered toxicant sensitivity pattern. As
      second approach, markers known to be relevant for the intended use of the cells
      were specifically tested. The "ATCC" cells rapidly down-regulated the dopamine
      transporter and tyrosine-hydroxylase after differentiation, while "UKN" cells
      maintained functional levels. As the respective genes were not altered
      themselves, we conclude that polygenic complex upstream changes can have drastic
      effects on biochemical features and toxicological responses of relatively similar
      SP of cells.

PMID- 30298210
TI  - Does 3-T fetal MRI induce adverse acoustic effects in the neonate? A preliminary
      study comparing postnatal auditory test performance of fetuses scanned at 1.5 and
      3 T.
AB  - BACKGROUND: Fetal MRI at 3 T is associated with increased acoustic noise relative
      to 1.5 T. OBJECTIVE: The goal of this study is to determine if there is an
      increased prevalence of congenital hearing loss in neonates who had a 3-T
      prenatal MR vs. those who had it at 1.5 T. MATERIALS AND METHODS: We
      retrospectively identified all subjects who had 3-T fetal MRI between 2012 and
      2016 and also underwent universal neonatal hearing screening within 60 days of
      birth. Fetuses with incomplete hearing screening, magnetic resonance imaging
      (MRI) studies at both field strengths or fetuses affected by conditions
      associated with hearing loss were excluded. A random group of controls scanned at
      1.5 T was identified. Five subjects had repeat same-strength MRIs (one at 3 T and
      four at 1.5 T). The pass/fail rate of the transient otoacoustic emissions test
      and auditory brainstem response test were compared using the Fisher exact test. A
      logistic regression was performed to assess the effects of other known risk
      factors for congenital hearing loss. RESULTS: Three hundred forty fetal MRI
      examinations were performed at 3 T, of which 62 met inclusion criteria. A control
      population of 1.5-T fetal MRI patients was created using the same exclusion
      criteria, with 62 patients randomly selected from the eligible population. The
      fail rates of transient otoacoustic emissions test for the 1.5-T and 3-T groups
      were 9.7% and 6.5%, respectively, and for the auditory brainstem response test
      were 3.2% and 1.6%, respectively. There was no significant difference in the fail
      rate of either test between groups (P=0.74 for transient otoacoustic emissions
      test, and P=0.8 for auditory brainstem response test). The median gestational age
      of the 3-T group was 30 weeks, 1 day, significantly higher (P<0.001) than the 1.5
      T group (median gestational age: 20 weeks, 2 days). CONCLUSION: Our findings
      suggest that the increase in noise associated with 3 T does not increase the rate
      of clinically detectable hearing abnormalities.

PMID- 30298211
TI  - Pilot study on renal magnetic resonance diffusion tensor imaging: are
      quantitative diffusion tensor imaging values useful in the evaluation of children
      with ureteropelvic junction obstruction?
AB  - BACKGROUND: Ureteropelvic junction (UPJ) obstruction is a common cause of renal
      injury in children. Indications for surgery are still controversial. Currently,
      there is no threshold to differentiate patients with suspected UPJ obstruction
      requiring surgery from the ones that do not, or to predict renal outcome after
      surgery. Several studies have demonstrated that diffusion tensor imaging (DTI)
      results may correlate with microstructural changes in the kidneys. OBJECTIVE: To
      evaluate the feasibility of using DTI to identify UPJ obstruction kidneys.
      MATERIALS AND METHODS: We analyzed functional MR urography (fMRU) with renal DTI
      (b=0 and b=400, 20 directions, 1.5 Tesla, no respiratory triggering) in 26
      kidneys of 19 children (mean age: 6.15 years) by comparing 13 kidneys with UPJ
      obstruction configuration that underwent pyeloplasty following the fMRU, and 13
      anatomically normal age- and gender-matched kidneys. DTI tractography was
      reconstructed using a fractional anisotropy threshold of 0.10 and an angle
      threshold of 55 degrees . User-defined regions of interest (ROIs) of the renal
      parenchyma (excluding collecting system) were drawn to quantify DTI parameters:
      fractional anisotropy, apparent diffusion coefficient (ADC), track length and
      track volume. The failure rate was evaluated. RESULTS: All DTI parameters changed
      with age; fractional anisotropy decreased (P<0.032). Track volume and track
      length increased (P<0.05). ADC increased with age in normal kidneys (P<0.001) but
      not in UPJ obstruction kidneys (P=0.11). After controlling for age, the
      fractional anisotropy (UPJ obstruction mean: 0.18, normal kidney mean: 0.21;
      P=0.001) and track length (UPJ obstruction mean: 11.9 mm, normal kidney mean:
      15.4 mm; P<0.001) were lower in UPJ obstruction vs. normal kidneys. There was a
      trend toward a higher ADC in UPJ obstruction kidneys vs. normal kidneys
      (P=0.062). The failure rate in UPJ obstruction kidneys due to technical
      limitations of DTI was 13/26 (50%). CONCLUSION: We demonstrated that fractional
      anisotropy is lower in UPJ obstruction than in normal kidneys. It is necessary to
      improve this technique to increase the success rate and to perform more studies
      to evaluate if a decrease in fractional anisotropy can differentiate UPJ
      obstruction kidneys from hydronephrotic kidneys without UPJ obstruction.

PMID- 30298212
TI  - An Automated Grading and Diagnosis System for Evaluation of Dry Eye Syndrome.
AB  - This article describes methods used to determine the severity of Dry Eye Syndrome
      (DES) based on Oxford Grading Schema (OGS) automatically by developing and
      applying a decider model. The number of dry punctate dots occurred on corneal
      surface after corneal fluorescein staining can be used as a diagnostic indicator
      of DES severity according to OGS; however, grading of DES severity exactly by
      carefully assessing these dots is a rather difficult task for humans. Taking into
      account that current methods are also subjectively dependent on the perception of
      the ophtalmologists coupled with the time and resource intensive requirements,
      enhanced diagnosis techniques would greatly contribute to clinical assessment of
      DES. Automated grading system proposed in this study utilizes image processing
      methods in order to provide more objective and reliable diagnostic results for
      DES. A total of 70 fluorescein-stained cornea images from 20 patients with mild,
      moderate, or severe DES (labeled by an ophthalmologist in the Keratoconus Center
      of Yildirim Beyazit University Ataturk Training and Research Hospital) used as
      the participants for the study. Correlations between the number of dry punctate
      dots and DES severity levels were determined. When automatically created scores
      and clinical scores were compared, the following measures were observed:
      Pearson's correlation value between the two was 0.981; Lin's Concordance
      Correlation Coefficients (CCC) was 0.980; and 95% confidence interval limites
      were 0.963 and 0.989. The automated DES grade was estimated from the regression
      fit and accordingly the unknown grade is calculated with the following formula:
      Gpred = 1.3244 log(Ndots) - 0.0612. The study has shown the viability and the
      utility of a highly successful automated DES diagnostic system based on OGS,
      which can be developed by working on the fluorescein-stained cornea images.
      Proper implemention of a computationally savvy and highly accurate classification
      system, can assist investigators to perform more objective and faster DES
      diagnoses in real-world scenerios.

PMID- 30298213
TI  - H3K4/K9 acetylation and Lr28-mediated expression of six leaf rust responsive
      genes in wheat (Triticum aestivum).
AB  - Development of leaf rust-resistant cultivars is a priority during wheat breeding,
      since leaf rust causes major losses in yield. Resistance against leaf rust due to
      Lr genes is partly controlled by epigenetic modifications including histone
      acetylation that is known to respond to biotic/abiotic stresses. In the present
      study, enrichment of H3K4ac and H3K9ac in promoters of six defense responsive
      genes (N-acetyltransferase, WRKY 40, WRKY 70, ASR1, Peroxidase 12 and Sarcosine
      oxidase) was compared with their expression in a pair of near-isogenic lines
      (NILs) for the gene Lr28 following inoculation with leaf rust pathotype '77-5';
      ChIP-qPCR was used for this purpose. The proximal and distal promoters of these
      genes contained a number of motifs that are known to respond to biotic stresses.
      The enrichment of two acetylation marks changed with passage of time; changes in
      expression of two of the six genes (N-acetyltransferase and peroxidase12),
      largely matched with changes in H3K4/H3K9 acetylation patterns of the two
      promoter regions. For example, enrichment of both the marks matched with higher
      expression of N-acetyltransferase gene in susceptible NIL and the deacetylation
      (H3K4ac) largely matched with reduced gene expression in resistant NIL. In
      peroxidase12, enrichment of H3K4ac and H3K9ac largely matched with higher
      expression in both the NILs. In the remaining four genes, changes in H3
      acetylation did not always match with gene expression levels. This indicated
      complexity in the regulation of the expression of these remaining four genes,
      which may be controlled by other epigenetic/genetic regulatory mechanisms that
      need further analysis.

PMID- 30298214
TI  - Incidental finding of subgemmal neurogenous plaque upon retrospective evaluation
      of oral lymphoepithelial cysts.
AB  - PURPOSE: We aimed to compare the histomorphological features of oral
      lymphoepithelial cysts (OLC) in different locations of the oral cavity and to
      verify the association between oral lymphoepithelial cysts and subgemmal
      neurogenous plaque (SNP) on biopsies from the lateral border of the tongue.
      METHODS: All cases diagnosed as OLC from the Oral Pathology Service at the School
      of Dentistry/University of Sao Paulo were retrieved. For all the cysts located in
      the tongue, their association to SNP was analyzed. Immunohistochemical staining
      against S100 was performed to confirm the diagnosis of SNP. RESULTS: Thirty-one
      cases were selected for morphological analysis and SNP was identified in 40% of
      cases, all of them positive for S100. In these cases, macroscopic analysis
      demonstrated two independent fragments. Microscopic analysis showed that cysts
      located in the floor of the mouth and ventral surface of the tongue showed less
      intense exocytosis, less formation of lymphoid follicles, and predominantly a
      moderate inflammatory infiltrate. CONCLUSIONS: OLC have a similar histological
      pattern regardless the location within the oral cavity and. In some cases, the
      biopsy specimen may be accompanied by a SNP as an adjacent independent structure.

PMID- 30298215
TI  - More women gynecologists in Belgium: assessment of changes in the workforce-a
      survey.
AB  - CONTEXT AND OBJECTIVE: International data highlight the increasing participation
      of women in the workforce in the medical field and particularly among
      obstetricians and gynecologists (OB-GYN). Some studies reported a gender
      difference in work productivity and practice patterns. The aim of this study is
      to analyze whether disparities exist between male and female OB-GYN in their
      practices with potential consequences for the organization of the OB-GYN
      departments. METHODS: A survey of all active, Belgian OB-GYNs concerning their
      professional activity and well-being and a survey of the heads of OG departments
      evaluating the impact of feminisation on their department. RESULTS: The response
      rate was 43% (n = 615). Women and men worked a similar number of half-days per
      week, respectively, 10.1 +/- 2.4 and 10.3 +/- 3.2 (p = 0.26) but women treated
      less patients per week (80 versus 90, p = 0.034). Pear year, women and men
      perform, respectively, 108 and 184 surgical procedures (p = 0.0001) plus 114 and
      100 deliveries (p = 0.09). Female OB-GYNs have fewer children but the size of
      their family has no bearing on work hours. Qualitatively, most OB-GYN regardless
      of their gender, consider their profession to be gratifying. Dissatisfaction is
      related to organizational concerns for women and to pressure of competitiveness
      for men. Women are more concerned about their private life and men more focussed
      on their professional career. However, both expressed the primary importance of
      good health and quality of life. A majority (66%) of head of departments do not
      consider that the feminisation of their staff is problematic. CONCLUSION: There
      was no difference in time spent at work between male and female OB-GYN. The
      number of patients treated by female OB-GYN per week is smaller which means that
      the time spent per patient is higher. The OG profession does not appear to be
      jeopardized by its feminisation according to this study and the opinion of the
      head of departments. Nevertheless, we need to take into account when organizing
      the future workforce that women tend to focus more on the time spent with
      patients than on surgical procedures.

PMID- 30298216
TI  - [CPAP usage problems and second-line therapy for obstructive sleep apnea].

PMID- 30298217
TI  - [Diagnoses of thyroid disorders in ENT and general practices in Germany between
      2008 and 2016].
AB  - OBJECTIVE: The aim of this study was to investigate thyroid disorder diagnoses in
      otorhinolaryngologic (ENT) practices in Germany compared to general (GP)
      practices using data from a representative Germany-wide practice database.
      METHODS: The database was retrospectively searched for diagnoses of thyroid
      disorders made in ENT and GP practices between January 2008 and December 2016.
      Data were collected on the most common three-character disease classes
      (categories) from the "Disorders of thyroid gland" (E00-E07) group as well as the
      "Benign neoplasm of thyroid gland" (D34) and "Malignant neoplasm of thyroid
      gland" (C73) categories. The periods 2008-2010, 2011-2013, and 2014-2016 were
      evaluated. RESULTS: The database included 71 ENT and 506 GP practices with
      continuous participation from 2008 to 2016. The relative frequency
      (patients/practice) of diagnoses from the "Disorders of thyroid gland" group was
      4.4-times higher in GP than in ENT practices. The relative frequency of benign
      neoplasms of the thyroid gland was 5-times higher in GP than in ENT practices.
      The relative frequency of malignant neoplasms of the thyroid gland was almost
      identical in GP and ENT practices. The most frequent diagnoses in both ENT and GP
      practices were found in the categories "Other nontoxic goiter" (E04) and "Other
      hypothyroidism" (E03). Diagnoses in the categories "Hyperthyroidism" (E05) and
      "Thyroiditis" (E06) were less frequent. Diagnoses of thyroid neoplasms were the
      least frequent, with benign neoplasms diagnosed more frequently in GP practices
      and malignant neoplasms diagnosed more frequently in ENT practices. During the
      study period, the diagnostic frequency of thyroid diseases decreased in ENT
      practices, whereas it increased in GP practices. CONCLUSION: Despite the
      increasing interest in establishing thyroid surgery in ENT clinics in Germany in
      recent years, thyroid diagnoses in ENT practices in Germany have been
      continuously declining, whereas they have considerably increased in GP practices.
      The reason for this may be health insurance provider-related differences in
      reimbursement practices for GPs and specialists.

PMID- 30298219
TI  - Herpes zoster infection and statins: which implications in clinical practice?
AB  - Herpes zoster (HZ), which is caused by reactivation of latent varicella zoster
      virus (VZV), constitutes a major public health concern in both short- and long
      term periods. Over the last years, several epidemiological studies have
      demonstrated that statin use is associated with increased risk of HZ at cerebral
      level. Because statins are among the most popular and best-selling drugs in
      western countries, this potential negative pleiotropic effect could have
      important implications in the daily clinical practice. In the present manuscript,
      we reviewed the available data on the statin use and the relative risk of HZ
      infection.

PMID- 30298218
TI  - Stem Cell Therapy in Cerebrovascular Disease.
AB  - PURPOSE OF REVIEW: The purpose of this article is to provide a review of state-of
      the-art cellular therapy in cerebrovascular diseases by discussing published and
      ongoing clinical trials. RECENT FINDINGS: In spite of the challenge in
      translating the success of cellular therapy in acute strokes from preclinical
      models to clinical trials, early phase clinical trial have recently shown promise
      in overcoming these challenges. Various stem cell types and doses are being
      studied, different routes of administration are under investigation, as well as
      defining the optimal time window to intervene. In addition, experimental methods
      to enhance cellular therapy, such as ischemic preconditioning, are evolving.
      After the failure of neuroprotectants in cerebrovascular diseases, researchers
      have been keen to provide a way of replacement of damaged brain tissue and to
      promote recovery in order to achieve better outcomes. The field has progressed
      from intravenous delivery in the 24- to 36-h time window to later intracerebral
      administration in chronic stroke in clinical trials. New optimism in acute stroke
      care fostered by the success of mechanical thrombectomy will hopefully extend
      into cell therapy to promote recovery.

PMID- 30298221
TI  - Evaluation of Childhood Vaccine Refusal and Hesitancy Intentions in Turkey:
      Correspondence.

PMID- 30298220
TI  - A common goodness-of-fit framework for neural population models using marked
      point process time-rescaling.
AB  - A critical component of any statistical modeling procedure is the ability to
      assess the goodness-of-fit between a model and observed data. For spike train
      models of individual neurons, many goodness-of-fit measures rely on the time
      rescaling theorem and assess model quality using rescaled spike times. Recently,
      there has been increasing interest in statistical models that describe the
      simultaneous spiking activity of neuron populations, either in a single brain
      region or across brain regions. Classically, such models have used spike sorted
      data to describe relationships between the identified neurons, but more recently
      clusterless modeling methods have been used to describe population activity using
      a single model. Here we develop a generalization of the time-rescaling theorem
      that enables comprehensive goodness-of-fit analysis for either of these classes
      of population models. We use the theory of marked point processes to model
      population spiking activity, and show that under the correct model, each spike
      can be rescaled individually to generate a uniformly distributed set of events in
      time and the space of spike marks. After rescaling, multiple well-established
      goodness-of-fit procedures and statistical tests are available. We demonstrate
      the application of these methods both to simulated data and real population
      spiking in rat hippocampus. We have made the MATLAB and Python code used for the
      analyses in this paper publicly available through our Github repository at
      https://github.com/Eden-Kramer-Lab/popTRT .

PMID- 30298222
TI  - Factor Structure and Criterion Validity of the Five Cs Model of Positive Youth
      Development in a Multi-University Sample of College Students.
AB  - There is growing recognition that clinical and developmental outcomes will be
      optimized by interventions that harness strengths in addition to ameliorating
      deficits. Although empirically-supported methods for identifying strengths are
      available for children and adolescents, this framework has yet to be applied to
      emerging adulthood. This study evaluates the nature of the Five Cs model of
      Positive Youth Development (PYD) - character, confidence, competence, connection,
      and caring - in a sample of emerging adults from six universities (N = 4654; 70%
      female; 81% White). Historically, PYD has been modeled as either separate
      correlated factors or a second-order factor structure. More recently, the
      bifactor model has been recommended to determine the degree to which PYD is
      unidimensional versus multidimensional. The present study examined the
      multidimensionality of PYD by comparing the model fit of a one-factor, five
      correlated factor model, and second-order factor structure with a bifactor model
      and found support for the bifactor model with evidence of invariance across sex.
      Criterion validity was also assessed using three criterion measures particularly
      relevant for adjustment during emerging adulthood: anxiety, depressive symptoms,
      and emotion regulation difficulties. PYD and the residual Cs tended to correlate
      negatively with indicators of maladaptive development. Future directions
      including applications of the PYD framework as a measure of thriving across
      emerging adulthood are discussed.

PMID- 30298223
TI  - It Gets Better: Attenuated Associations Between Latent Classes of Peer
      Victimization and Longitudinal Psychosocial Outcomes in Four Low-Resource
      Countries.
AB  - Very few studies of peer victimization have been conducted in low-resource
      countries, where cultural and contextual differences are likely to influence the
      dynamics of these experiences in ways that may reduce the generalizability of
      findings of the larger body of literature. Most studies in these settings are
      also subject to multiple design limitations that restrict our ability to
      understand the dynamics of peer victimization experiences. Person-centered
      approaches such as latent class analysis are an improvement on more traditional
      modeling approaches as they allow exploration of patterns of victimization
      experiences. The goal of the current study was to examine associations between
      patterns of peer victimization in adolescence and both concurrent and
      longitudinal psychosocial adjustment. Data were included for 3536 youth (49.6%
      female) in Ethiopia, India, Peru, and Vietnam to examine associations between
      adolescent peer victimization and indicators of poor psychosocial adjustment.
      Previously derived latent classes of peer victimization based on youth self
      report of past-year exposure to nine forms of peer victimization at age 15 were
      used to predict self-reported emotional difficulties, self-rated health, and
      subjective wellbeing at ages 15 and 19 while controlling for sex. The findings
      show that at age 15, victimization was associated with higher emotional
      difficulties in all settings, lower subjective wellbeing in all except Peru, and
      lower self-rated health in Vietnam. At follow-up, all associations had attenuated
      and were largely non-significant. Sensitivity analyses confirmed the robustness
      of these results. These findings illustrate the multifinality of outcomes of peer
      victimization, suggesting social and developmental influences for potential
      pathways of resilience that hold promise for informing interventions and supports
      in both low and high resource settings.

PMID- 30298224
TI  - The Consequences of Adolescent Delinquent Behavior for Adult Employment Outcomes.
AB  - Delinquent behavior is common during adolescence and may disrupt trajectories of
      labor market attainment. Estimates of the relationship between delinquency and
      employment are threatened by selection bias, as youth who engage in delinquency
      often differ substantially from youth who do not. The current study examined the
      association between adolescents' engagement in serious delinquency and four
      measures of occupational attainment in young adulthood: unemployment, personal
      earnings, employer-provided benefits, and occupational earnings. It examined the
      effect of delinquency independent of between-person differences in a variety of
      attributes and tested whether the hypothesized relationship was mediated by
      educational attainment, work experience, disconnectedness from both education and
      work, or criminal justice sanctioning. This study analyzed data from the first
      four waves of the National Longitudinal Survey of Adolescent to Adult Health (Add
      Health), yielding an analytic sample of 14,800 (51% female, mean age 16 years).
      The Wave 1 Add Health survey was administered in 1994-1995, and Wave 4 of the
      survey was administered in 2007-2008. The analytic strategy, propensity score
      weighting, produced estimates that were less biased by differences between youth
      who had and who had not engaged in delinquent behavior. The study found that
      delinquency was significantly associated with the likelihood of being unemployed:
      compared to non-delinquents, delinquents were more likely to be unemployed even
      after controlling for temporally prior traits and resources, human capital, and
      criminal justice contact. The results provided more qualified support for
      hypothesized relationships between delinquency and job quality. The study
      concluded that offending may result in less fruitful job searches, but once a
      search results in employment, employed delinquents are not readily discernible
      from employed non-delinquents in the quality of their jobs. These conclusions
      contribute to literature on the labor market outcomes of people with histories of
      adolescent delinquency as they enter young adulthood.

PMID- 30298225
TI  - Talking Together, Thinking Alone: Relations among Co-Rumination, Peer
      Relationships, and Rumination.
AB  - Girls are more likely to engage in rumination, associated with the development of
      mental health problems, as well as report higher levels of friendship quality,
      hypothesized to protect against these disorders. The current study examined
      whether co-rumination may drive simultaneous increases in rumination and changes
      in friendship quality among adolescents. The project included 360 participants
      (43% boys), ages 9.8 to 15.8 years, and analyses revealed that co-rumination
      mediated the link between female sex and both rumination and negative friendship
      quality. There was also a bidirectional relation between co-rumination and
      positive friendship quality. These findings highlight several pathways by which
      co-rumination mediates the relation between sex and both maladaptive (i.e.
      rumination, negative friendship quality) and adaptive (i.e. positive friendship
      quality) outcomes.

PMID- 30298226
TI  - Hypertensive Crisis with Neurological Impairment Mimicking a Guillain-Barre
      Syndrome: Searching for a Link.
AB  - Guillain-Barre syndrome (GBS) may be complicated by severe hypertension (HT) and
      in turns severe HT can occur with neurological damage mimicking a GBS, so that
      underlying causes should be investigated. We describe a case of a 62-year-old
      woman presented to the emergency department for hypertensive crisis with
      symmetric flaccid paralysis, hypotonia and hyporeflexia of both upper and lower
      limbs. Brain computed tomography, magnetic resonance imaging and lumbar puncture
      were normal. Laboratory investigations revealed severe hypokalemia, renal
      failure, liver impairment, rabdomyolysis, metabolic alkalosis, and low plasma
      renin and aldosterone levels. Continuous potassium replacement led to complete
      clinical resolution. A detailed history revealed chronic intake of 250 g/day
      black liquorice. Hypokalaemic muscle weakness may simulate a GBS. When serum
      potassium level falls below 2.5 mmol/l, rhabdomyolysis may occur. In this
      clinical case, an apparent mineralocorticoid excess syndrome was induced by
      chronic ingestion of liquorice. This latter contains the glycyrrhetic acid that
      inhibits the enzyme 11-beta-hydroxysteroid dehydrogenase enzyme type-2 leading an
      aldosterone-like effect and causing hypertension, hypokalemia, metabolic
      alkalosis and low renin values. The clinical presentation is similar to that
      observed in the primary aldosteronism, but in this syndrome plasma aldosterone
      levels are low rather than elevated as in primary aldosteronism. Liquorice
      induced hypertension with severe hypokalemia and rhabdomyolysis is a rare
      condition and the initial presentation with acute muscle paralysis is still more
      unusual. Before performing instrumental examinations in middle-aged peoples with
      hypertension crisis and neurological impairment, a detailed clinical history is
      mandatory.

PMID- 30298227
TI  - Short-Term and Mid-Term Results of Minimally Invasive Occlusion of Ventricular
      Septal Defects via a Subaxillary Approach in a Single Center.
AB  - This retrospective, single-center study evaluated short-term and mid-term results
      of minimally invasive surgery to occlude ventricular septal defects (VSDs) using
      a subaxillary approach. The procedure was performed on 429 children (224 boys,
      205 girls; age 2.4 +/- 2.5 years; mean weight 12.7 +/- 10.1 kg) between January
      2014 and December 2016 at the Children's Heart Center of Henan Province People's
      Hospital. An approximately 2-cm subaxillary incision was made between the third
      and fifth ribs, and the appropriate right atrium or ventricle was punctured under
      the guidance of transencephalographic echocardiography (TEE). The VSD was then
      occluded under TEE guidance. The mean size of the VSDs was 4.2 +/- 1.0 mm, and
      the occluder measured 5.3 +/- 1.3 mm. Asymmetrical occluders were used in 44
      patients and symmetrical occluders in 385 patients. The operative time was 60.7
      +/- 21.3 min, and time in the intensive care unit was 20.9 +/- 6.5 h. Blood loss
      was 12.4 +/- 14.4 ml. There were no deaths among these patients. Occluder
      displacement occurred in two cases. There were no complications (e.g., third
      degree atrioventricular block, new aortic regurgitation, reoperation for massive
      bleeding, serious infection). All patients were followed for 6-48 months, during
      which time there were ten cases of a postoperative residual shunt, which self
      closed in eight during follow-up. The other two cases are still being followed.
      No complications occurred during follow-up (e.g., reoperation, aortic
      regurgitation, atrioventricular block, occluder abscission). Occluding VSDs using
      the subaxillary approach is safe and effective. Short-term and mid-term results
      are satisfactory. Further follow-up is required regarding long-term results.

PMID- 30298228
TI  - Ticks in the Lion City: a preliminary review of the tick fauna of Singapore.
AB  - To this day, the tick fauna of Singapore remains poorly known. Although several
      studies of select species have been undertaken within Singapore, much of the
      information regarding Singaporean ticks is fragmentary. To facilitate future
      study of this group, the scattered information on Singaporean ticks is
      synthesised in the present work and includes a preliminary checklist of species
      reported to occur in Singapore, which comprised 14 species in 5 genera, with
      confirmed records of Argas pusillus, Amblyomma nitidum, Amblyomma varanense,
      Haemaphysalis doenitzi, Haemaphysalis nadchatrami, Haemaphysalis semermis, Ixodes
      granulatus, Rhipicephalus microplus, and Rhipicephalus sanguineus, and
      unconfirmed reports of Amblyomma cordiferum, Amblyomma geoemydae, Amblyomma
      helvolum, Amblyomma javanense and Amblyomma testudinarium.

PMID- 30298229
TI  - Characterisation of cattle anal odour constituents associated with the repellency
      of Rhipicephalus appendiculatus.
AB  - Adults of the Brown Ear Tick (Rhipicephalus appendiculatus) have a predilection
      for feeding inside and around the ears of cattle and other hosts. A previous
      study has shown that the tick locates the host ears by 'push-pull' deployment of
      a repellent blend emitted at the anal region and an attractant blend emitted at
      the ears. Interestingly, the two odours play reverse roles with Rhipicephalus
      evertsi, which prefer to feed around the anal region. The present study was
      undertaken to characterize the major constituents of the cattle anal odour and to
      evaluate their repellence to R. appendiculatus. The anal odour was trapped with
      reverse-phase C18-bonded silica, Porapak Q and Super Q placed in an oven bag
      attached at the anal region of the cattle for 6 h. The adsorbents were then
      removed and extracted with dichloromethane, and the extracted compounds analyzed
      by linked gas chromatography-mass spectrometry (GC-MS). The major constituents of
      the odour were o-xylene, 4-hydroxy-4-methyl-2-pentanone, 4-methyl-2
      methoxyphenol, ethylbenzene, 2,6,6-trimethyl
      [1S(1alpha,beta,5alpha)]bicycloheptanes, 5-ethoxydihydro-2(3H)-furanone, 3
      methylene-2-pentanone, 5-methyl-2-phenyl-1H-indole, and 3-pentanone. The
      repellency of the available compounds (o-xylene, 4-hydroxy-4-methyl-2-pentanone,
      4-methyl-2-methoxyphenol, ethyl benzene, 3-methylene-2-pentanone, and 3
      pentanone) and blends was evaluated using a dual choice tick climbing assay at
      different doses. The anal odour showed repellence with RD75 of 0.39. Of the
      compounds tested, 4-methyl-2-methoxyphenol was found to be most repellent (RD75 =
      0.56) and 3-pentanone least repellent (RD75 = 622.7). The blend of the six
      constituents showed RD75 of 0.34, comparable to that of the crude anal odour
      blend. A series of subtractive bioassays with one constituent of the 6-component
      blend missing was also carried out. Subtraction of 3-methylpentanone gave the
      most repellent blend (RD75 = 0.097), whereas subtraction of 4-methylguaiacol gave
      the least repellent blend (RD75 = 160.7) consistent with the high individual
      activity of this phenol. The study lays down useful groundwork for on-host
      deployment of controlled-release of a selected repellent or blend to disrupt the
      tick's ability to locate its preferred feeding site.

PMID- 30298230
TI  - A morphological and phylogenetic analysis of Ornithodoros marinkellei (Acari:
      Argasidae), with additional notes on habitat and host usage.
AB  - Ornithodoros marinkellei was described from larvae collected on Pteronotus spp.
      bats in Colombia and Panama. More recently, this tick was reported in the
      Brazilian Amazon. Because some morphometric differences were observed between O.
      marinkellei larvae from Colombia and Brazil, it was proposed that further
      investigations were needed to assess whether the differences could be attributed
      to intra- or inter-specific polymorphism. Herein, we collected O. marinkellei
      specimens in the type locality of Colombia, in Brazil, and in a new locality in
      Nicaragua, expanding the distribution of the species to Nicaragua. Morphometric
      analysis of larvae and adults, corroborated by a principal component analysis
      (PCA), indicated that the Brazilian specimens were larger than specimens from
      Colombia and Nicaragua. Phylogenetic analysis inferred from the mitochondrial 16S
      rRNA gene showed ticks from Colombia and Nicaragua more genetically related than
      any of them with ticks from Brazil, although ticks from the three countries
      grouped in a clade sister to a major clade containing sequences of various
      Neotropical Ornithodoros species. We concluded that ticks identified as O.
      marinkellei from Colombia, Nicaragua, and Brazil represent the same taxon, and
      that the genetic and morphological differences between them are likely to have a
      geographical bias. We redescribed the nymph of O. marinkellei, which has a
      vestigial hypostome, probably incompatible with blood feeding. We also report
      human infestation by O. marinkellei adults. As all reports of O. marinkellei
      adults have been from hot caves (temperature > 35  degrees C), this abiotic
      condition could be a limiting factor for the occurrence of this tick species.

PMID- 30298231
TI  - In search of the vector(s) of Babesia rossi in Nigeria: molecular detection of B.
      rossi DNA in Rhipicephalus sanguineus sensu lato (Acari: Ixodidae) ticks
      collected from dogs, circumstantial evidence worth exploring.
AB  - The brown dog tick Rhipicephalus sanguineus (sensu lato) (Acari: Ixodidae) has a
      cosmopolitan distribution, is a proven vector of a host of pathogens with
      emerging evidence incriminating it in the transmission of some others.
      Specifically it is reputed as the main vector of Babesia vogeli whereas the
      southern African yellow dog tick Haemaphysalis elliptica, long considered to be
      H. leachi, is apparently the only proven vector of B. rossi, since the
      resurrection of the separate species H. elliptica as a member of the leachi-group
      by Apanaskevich et al. However, recent epidemiological surveys conducted in
      Nigeria show higher prevalence of B. rossi than B. vogeli infection in dogs most
      of whom were infested with R. sanguineus and rarely with ticks of the H. leachi
      group. The discrepancy between tick distribution and Babesia spp. prevalent in
      dogs stimulated us to investigate the possible role of R. sanguineus (s.l.) in
      the natural transmission of B. rossi. Out of a total of 66 tick samples
      identified morphologically and molecularly as R. sanguineus collected from dogs
      manifesting clinical signs of tick-borne diseases, eight (12%) were positive in
      nested PCR for Babesia sp. DNA. Sequencing results for these amplified products
      showed that all of the 18S rDNA sequences (693 bp) were identical to each other,
      and bore 99.3-99.9% identities with those from other B. rossi isolates accessible
      in GenBank. None of the ticks harbored the DNA of B. vogeli or B. canis. The
      possible implications for the detection of B. rossi DNA in R. sanguineus (s.l.)
      ticks collected from dogs in the epidemiology of B. rossi infection of dogs in
      Nigeria is highlighted.

PMID- 30298232
TI  - The first authenticated record of the pangolin tick Amblyomma javanense (Acari:
      Ixodidae) in Singapore, with notes on its biology and conservation.
AB  - The first authenticated record of the co-endangered pangolin tick (Amblyomma
      javanense) is reported from the Republic of Singapore, based on specimens of
      males and females collected from the Sunda pangolin (Manis javanica). The biology
      of the species is reviewed and steps for its conservation are outlined to ensure
      its continued survival across its range.

PMID- 30298233
TI  - Systematic Review and Meta-analysis of Short- versus Long-Acting Granulocyte
      Colony-Stimulating Factors for Reduction of Chemotherapy-Induced Febrile
      Neutropenia.
AB  - INTRODUCTION: Short- and long-acting granulocyte-colony stimulating factors (G
      CSFs) are approved for the reduction of febrile neutropenia. A systematic
      literature review was performed to identify randomized controlled trials (RCTs)
      and non-RCTs reporting the use of G-CSFs following chemotherapy treatment.
      METHODS: Medline(r)/Medline in-process, Embase(r), and the Cochrane Library were
      searched for studies published between January 2003 and June 2016. A hand-search
      of relevant conference proceedings was conducted for meetings held between 2012
      and 2016. Eligible studies were restricted to those reporting a direct, head-to
      head comparison of short- versus long-acting G-CSFs for reduction of chemotherapy
      induced febrile neutropenia. Risk-of-bias assessments were performed for full
      publications only. RESULTS: The search strategy yielded 4044 articles for
      electronic screening. Thirty-six publications were evaluated for the meta
      analysis: 11 of 12 RCTs and 2 of 24 non-RCTs administered doses of the short
      acting G-CSF filgrastim for >= 7 days. In RCT studies, there was no statistically
      significant difference in outcomes of interest between short- and long-acting G
      CSFs. In non-RCTs, the overall risk was lower with long-acting G-CSF than with
      short-acting G-CSF for incidence of febrile neutropenia [overall relative risk
      (RR) = 0.67, P  = 0.023], hospitalizations (overall RR = 0.68, P  < 0.05), and
      chemotherapy dose delays (overall RR = 0.68, P  = 0.020). CONCLUSIONS: Overall,
      the weight of evidence from RCTs indicates little difference in efficacy between
      the short- and long-acting G-CSFs if dosed according to recommended guidelines.
      There is some evidence for greater efficacy for long-acting G-CSFs in non-RCTs,
      which may be a result of under-dosing of short-acting G-CSFs in general practice
      in real-world usage. FUNDING: Hospira Inc, which was acquired by Pfizer Inc in
      September 2015, and Pfizer Inc.

PMID- 30298234
TI  - How the stimulus influences mind wandering in semantically rich task contexts.
AB  - What do we think about when we mind wander and where do these thoughts come from?
      We tested the idea that semantically rich stimuli yield patterns of mind
      wandering that are closely coupled with the stimuli compared to being more
      internally triggered. We analyzed the content of 949 self-reported zone outs
      (1218 thoughts) and 519 of their triggers from 88 participants who read an
      instructional text and watched a film for 20 min each. We found that mind
      wandering associated with memory retrieval was more frequent than prospection and
      introspection across both stimuli. Over 70% of autobiographical and semantic
      memory retrievals were triggered by the content of the stimuli, compared to
      around 30% for prospective and introspective thoughts. Further, latent semantic
      analysis revealed that semantic and unspecific memories were more "semantically"
      similar to their triggers than prospective and introspective thoughts, suggesting
      that they arise from spontaneous associations with the stimulus. These findings
      suggest a re-evaluation of how internal concerns and the external world give rise
      to mind wandering and emphasize the importance of studying mind wandering in
      semantically rich contexts akin to much of the real world.

PMID- 30298235
TI  - Antimicrobial resistance: a global one-health problem for all ages.

PMID- 30298236
TI  - Is the genetic variability of Cathepsin B important in the pathogenesis of
      Blastocystis spp.?
AB  - The potential role of Blastocystis as a pathogen is controversial because it is
      found in both symptomatic and asymptomatic carriers. Since Cathepsin B has been
      identified as a main virulence factor that contributes to the pathogenesis of
      this parasite, the purpose of this study was to analyze the genetic polymorphisms
      of cathepsin B from Blastocystis from patients with irritable bowel syndrome and
      from asymptomatic carriers. DNA from fecal samples of both groups, which were
      previously genotyped by 18S sequencing, was used to amplify a fragment of the
      cathepsin B gene. Phylogenetic reconstructions were performed and some genetic
      population indexes were obtained. Amplicons of 27 samples (15 cases, 10 controls,
      and two commercial ATCC strains) were obtained and analyzed. Phylogenetic
      reconstructions using nucleotides or inferred amino acid sequences did not
      separate between cases or controls or among subtypes. Regarding the values of
      genetic variability, we found that the haplotype and nucleotide diversity indexes
      of cathepsin B from cases and controls were similar to the values of 18S from
      controls. By contrast, 18S from cases showed low variability, suggesting that the
      genetic variability of cathepsin B was not related to the symptomatology of
      Blastocystis carriers. However, since no polymorphisms related to cases or
      controls were found, it is logical to assume that the potential damage caused by
      Blastocystis in situ may be due to unclear mechanisms of Cathepsin B regulation
      and expression that should be studied in future studies.

PMID- 30298237
TI  - Ortholinea concentrica n. sp. (Cnidaria: Myxozoa) from the Patagonian seabass
      Acanthistius patachonicus (Jenyns, 1840) (Perciformes: Serranidae) off Patagonia,
      Argentina.
AB  - The Patagonian seabass Acanthistius patachonicus (Jenyns, 1840) (Serranidae) is a
      marine fish valued for commercial and sport fisheries from Argentina. We report a
      new myxosporean (Cnidaria: Myxozoa) infecting the urinary system of the
      Patagonian seabass from San Antonio Bay, San Matias Gulf, on the Atlantic Ocean.
      The mature myxospores were subspherical, 8.2-11.0 MUm * 7.9-11.0 MUm and 7.7-9.0
      MUm in thickness; two subspherical polar capsules, 2.4-3.8 MUm * 2.3-3.6 MUm,
      with 3 to 4 turns of the polar tubule; openings on different valves in almost
      opposite directions. Ornamented shell valves exhibited 17-20 concentrically
      organized surface ridges. SSU rDNA phylogenetics analyses placed the new species
      in the freshwater urinary tract clade, clustering in a clade formed by
      Myxobilatus gasterostei (Parisi, 1912), Acauda hoffmani Whipps, 2011, and other
      Ortholinea spp. Based on spore morphology, site of infection, and molecular data,
      we described this myxozoan as Ortholinea concentrica n. sp.

PMID- 30298238
TI  - Neural correlates of proactive and reactive inhibition of saccadic eye movements.
AB  - Although research on goal-directed, proactive inhibitory control (IC) and
      stimulus-driven, reactive IC is growing, no previous study has compared proactive
      IC in conditions of uncertainty with regard to upcoming inhibition to conditions
      of certain upcoming IC. Therefore, we investigated effects of certainty and
      uncertainty on behavior and blood oxygen level dependent (BOLD) signal in
      proactive and reactive IC. In two studies, healthy adults performed saccadic
      go/no-go and prosaccade/antisaccade tasks. The certainty manipulation had a
      highly significant behavioral effect in both studies, with inhibitory control
      being more successful under certain than uncertain conditions on both tasks (p <=
      0.001). Saccadic go responses were significantly less efficient under conditions
      of uncertainty than certain responding (p < 0.001). Event-related functional
      magnetic resonance imaging (fMRI) (one study) revealed a dissociation of
      certainty- and uncertainty-related proactive inhibitory neural correlates in the
      go/no-go task, with lateral and medial prefrontal and occipital cortex showing
      stronger deactivations during uncertainty than during certain upcoming
      inhibition, and lateral parietal cortex being activated more strongly during
      certain upcoming inhibition than uncertainty or certain upcoming responding. In
      the antisaccade task, proactive BOLD effects arose due to stronger deactivations
      in uncertain response conditions of both tasks and before certain prosaccades
      than antisaccades. Reactive inhibition-related BOLD increases occurred in
      inferior parietal cortex and supramarginal gyrus (SMG) in the go/no-go task only.
      Proactive IC may imply focusing attention on the external environment for
      encoding salient or alerting events as well as inhibitory mechanisms that reduce
      potentially distracting neural processes. SMG and inferior parietal cortex may
      play an important role in both proactive and reactive IC of saccades.

PMID- 30298239
TI  - Opportunities for Early Intervention to Avoid Prolonged Work Disability:
      Introduction to the Special Section.
AB  - Purpose The articles in this special section examine opportunities for early
      intervention that is intended to retain the jobs of workers who have medical
      conditions that could put them at risk of prolonged work disability. Methods The
      first three articles examine options for analyzing various types of disability
      claims data for targeting early intervention; the fourth article provides new
      information from 50 case studies on how employers decide to invest in the
      retention of individual workers. Results Together, the four articles demonstrate
      that there may be an opportunity to positively affect longer-term outcomes for
      workers with medical conditions. This would be accomplished by building and
      expanding on existing systems in order to efficiently identify, and provide
      timely support to, workers with medical conditions in a critical period during
      which the decisions and actions of various stakeholders, including the workers
      themselves, may have a major influence on these outcomes. Conclusions Forthcoming
      opportunities to develop, implement, and test evidence-based interventions to
      promote job retention can provide further insight into the value of the options
      described in the articles.

PMID- 30298241
TI  - Self-Stigma Reduction Interventions for People Living with HIV/AIDS and Their
      Families: A Systematic Review.
AB  - Stigma is a primary concern for people living with human immunodeficiency virus
      (HIV)/AIDS (PLWHA), and has great impact on their and their family members'
      health. While previous reviews have largely focused on the public stigma, this
      systematic review aims to evaluate the impact of HIV/acquired immunodeficiency
      syndrome (AIDS)-related self-stigma reduction interventions among PLWHA and their
      families. A literature search using eight databases found 23 studies meeting the
      inclusion criteria. Five types of intervention approaches were identified: (1)
      psycho-educational intervention, (2) supportive intervention for treatment
      adherence (antiretroviral therapy), (3) psychotherapy intervention, (4) narrative
      intervention, and (5) community participation intervention. Overall, the reviewed
      articles suggested a general trend of promising effectiveness of these
      interventions for PLWHA and their family members. Psycho-educational
      interventions were the main approach. The results highlighted the need for more
      interventions targeting family members of PLWHA, and mixed-methods intervention
      studies.

PMID- 30298242
TI  - Test Result Management Practices of Canadian Internal Medicine Physicians and
      Trainees.
AB  - BACKGROUND: Missed test results are a cause of medical error. Few studies have
      explored test result management in the inpatient setting. OBJECTIVE: To examine
      test result management practices of general internal medicine providers in the
      inpatient setting, examine satisfaction with practices, and quantify self
      reported delays in result follow-up. DESIGN: Cross-sectional survey.
      PARTICIPANTS: General internal medicine attending physicians and trainees
      (residents and medical students) at three Canadian teaching hospitals. MAIN
      MEASURES: Methods used to track test results; satisfaction with these methods;
      personal encounters with results respondents "wish they had known about sooner."
      KEY RESULTS: We received surveys from 33/51 attendings and 99/108 trainees
      (response rate 83%). Only 40.9% of respondents kept a record of all tests they
      order, and 50.0% had a system to ensure ordered tests were completed. Methods for
      tracking test results included typed team sign-out lists (40.7%), electronic
      health record (EHR) functionality (e.g., the electronic "inbox") (38.9%), and
      personal written or typed lists (14.8%). Almost all trainees (97.9%) and
      attendings (81.2%) reported encountering at least one test result they "wish they
      had known about sooner" in the past 2 months (p = 0.001). A higher percentage of
      attendings kept a record of tests pending at hospital discharge compared to
      trainees (75.0% vs. 35.7%, p < 0.001), used EHR functionality to track tests
      (71.4% vs. 27.5%, p = 0.004), and reported higher satisfaction with result
      management (42.4% vs. 12.1% satisfied or very satisfied, p < 0.001). CONCLUSIONS:
      Canadian physicians report an array of problems managing test results in the
      inpatient setting. In the context of prior studies from the outpatient setting,
      our study suggests a need to develop interventions to prevent missed results and
      avoid potential patient harms.

PMID- 30298240
TI  - The Impact of Interictal Discharges on Performance.
AB  - PURPOSE OF REVIEW: Our purpose is to review evidence relating to the concept that
      interictal epileptiform discharges (IEDs) impair brain performance. RECENT
      FINDINGS: Sophisticated measures of motor and cognitive performance have
      clarified older observations, confirming that in both animals and humans, IEDs
      affect aspects of performance, IED morphology, frequency, anatomical
      distribution, and duration matter. However, we now know that it is difficult to
      draw a line between IEDs and seizures, not only by electrical criteria but even
      by metabolic and molecular measures. IEDs impair performance acutely and probably
      chronically. Thus, there are good theoretical reasons for suppressing them, but
      no consensus has been reached on how much effort this deserves. Many
      antiepileptic medications effective for control of clinical seizures have little
      effect on IEDs. Better methods of measuring outcomes may allow selection of
      individual patients for whom treatment aimed at IEDs is worthwhile.

PMID- 30298243
TI  - Fragments of the second transmembrane helix of three G-protein-coupled receptors:
      comparative synthetic, structural and conformational studies.
AB  - We compared the synthesis and structural/conformational details of the (66-97)
      segments of the second transmembrane helix of AT1, MAS and B2, all of which
      belong to the class of G-protein-coupled receptors (GPCR). Step-by-step
      monitoring of the coupling reactions during the growth of these transmembrane
      peptides revealed that the increase in the level of difficulty started at the 6
      10 regions of the sequence. Possibly due to their long and hydrophobic sequences,
      the final estimated synthesis yields decreased progressively by up to 20-25%.
      Analytical high pressure liquid chromatography showed that the hydrophobicity
      indexes of each TM-8, -16, -24 and -32 segments correlated linearly with their
      retention time. Microscopic measurements of peptide-resin beads indicated that,
      in general, dichloromethane and dimethylsulfoxide were the best solvents for
      solvating resin beads in the initial and final stages of the synthesis,
      respectively. Results from electron paramagnetic resonance experiments with Toac
      (2, 2, 6, 6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) spin-labeled
      peptide resins revealed that the level of peptide chain mobility throughout the
      polymer network was in agreement with their swelling data measured in different
      solvents. Initial results regarding conformational features determined by
      circular dichroism (CD) spectra revealed typical alpha-helicoidally structures
      for MAS and B2 TM32 fragments when in more than roughly 30% (v/v)
      trifluoroethanol (TFE). In contrast, the AT1-TM32 segment revealed CD spectra,
      more representatives of a mixture of other secondary helical conformers,
      regardless of the amount of TFE. These findings observed in different aspects of
      these receptors' fragments support further investigations of GPCR-type
      macromolecules.

PMID- 30298244
TI  - Characterizing the Deep Terrestrial Subsurface Microbiome.
AB  - A large portion of the earth's biomass resides in the subsurface and recent
      studies have expanded our knowledge of indigenous microbial life. Advances in the
      field of metagenomics now allow analysis of microbial communities from low
      biomass samples such as deep (>2.5 km) shale core samples. Here we present
      protocols for the best practices in contamination control, handling core
      material, extraction of nucleic acids, and low-input library preparation for
      subsequent metagenomic sequencing.

PMID- 30298245
TI  - Freshwater Viromes: From Sampling to Evaluation.
AB  - There are a number of options available to researchers who wish to collect and
      analyze viral metagenomes (viromes) from environmental samples. Here we describe
      a laboratory procedure for generation of viromes from freshwater samples,
      specifically targeting dsDNA bacteriophages. We also discuss methods for
      bioinformatic analysis of the resulting data.

PMID- 30298246
TI  - Characterization of Eukaryotic Microbiome Using 18S Amplicon Sequencing.
AB  - With the advent of low-cost, high-throughput sequencing, taxonomic profiling of
      complex microbial communities through 16S rRNA marker gene surveys has received
      widespread interest, uncovering a wealth of information concerning the bacterial
      composition of microbial communities, as well as their association with health
      and disease. On the other hand, little is known concerning the eukaryotic
      components of microbiomes. Such components include single-celled parasites and
      multicellular worms that are known to adversely impact the health of millions of
      people worldwide. Current molecular methods to detect eukaryotic microbes rely on
      the use of directed PCR analyses that are limited by their inability to inform
      beyond the taxon targeted. With increasing interest to develop equivalent marker
      based surveys as used for bacteria, this chapter presents a stepwise protocol to
      characterize the diversity of eukaryotic microbes in a sample, using amplicon
      sequencing of hypervariable regions in the eukaryotic 18S rRNA gene.

PMID- 30298247
TI  - Culture and Molecular Profiling of the Respiratory Tract Microbiota.
AB  - Microbiome research of host-associated communities has been advanced recently
      through improvements in sequencing technologies and bioinformatic methods.
      Traditional microbiological culture, when combined with molecular techniques, can
      provide a sensitive platform to comprehensively study the airway microbiota. Here
      we describe the culture methods necessary to capture a large proportion of the
      airway microbiota and molecular methods for profiling bacterial communities
      through the 16S rRNA gene, which, when combined, offer a more complete picture of
      the diversity of airway microbial communities than either method alone.

PMID- 30298248
TI  - Methods and Strategies to Examine the Human Breastmilk Microbiome.
AB  - It has recently been discovered that breastmilk is not sterile, but contains a
      vast array of microbes, known collectively as the breastmilk microbiome. The
      breastmilk microbiome field is in its infancy, but over the last decade, our
      understanding of the microbial communities that inhabit the human body has
      increased exponentially, due in large part to novel next-generation sequencing
      technologies. These culture-independent, high-throughput molecular technologies
      have allowed biologists to investigate the entirety of microbiota present in
      breastmilk, which was previously poorly known. These approaches are novel and the
      methodologies surrounding the exploration of the breastmilk microbiota remain in
      flux. The objectives of this chapter are to outline what is known thus far and
      detail the optimal methods and strategies to conducting a breastmilk microbiome
      study from subject recruitment and milk collection to DNA extraction, high
      throughput sequencing and bioinformatics analyses.

PMID- 30298249
TI  - Quantification of Vitamin B12-Related Proteins in Marine Microbial Systems Using
      Selected Reaction Monitoring Mass Spectrometry.
AB  - Mass spectrometry-based proteomic approaches to studying microbial systems enable
      assessment of taxonomically resolved functional capacity. A subset of these
      proteomic approaches are absolutely quantitative, enabling comparisons of protein
      expression patterns between different studies and across environments. This
      chapter outlines a method for applying quantitative assays in marine microbial
      communities, using proteins involved in vitamin B12 (cobalamin) utilization and
      production as specific examples. This approach involves identifying important
      protein targets, determining taxonomic resolution of the required assays,
      identifying suitable peptides, developing and optimizing liquid chromatography
      selected reaction monitoring mass spectrometry assays (LC-SRM-MS), and processing
      the resulting data. Implementing the method outlined here results in measurements
      (fmol diagnostic peptide per MUg of total bulk protein) that, in this case,
      define the nutritional status of microbial community members with respect to
      vitamin B12, and are comparable across and between marine microbial systems.

PMID- 30298250
TI  - Single-Cell Genomics of Microbial Dark Matter.
AB  - Single-cell genomics allows bypassing the culturing step and to directly access
      environmental microbes one cell at a time. The method has been successfully
      applied to explore archaeal and bacterial candidate phyla, referred to as
      microbial dark matter. Here I summarize the single-cell genomics workflow,
      including sample preparation and preservation, high-throughput fluorescence
      activated cell sorting, cell lysis and amplification of environmental samples.
      Furthermore I describe phylogenetic screening based on 16S rRNA genes and suggest
      a suitable library preparation and sequencing approach.

PMID- 30298251
TI  - 16S rRNA Gene Analysis with QIIME2.
AB  - Microbial marker-gene sequence data can be used to generate comprehensive
      taxonomic profiles of the microorganisms present in a given community and for
      other community diversity analyses. The process of going from raw gene sequences
      to taxonomic profiles or diversity measures involves a series of data
      transformations performed by numerous computational tools. This includes tools
      for sequence quality checking, denoising, taxonomic classification, alignment,
      and phylogenetic tree building. In this chapter, we demonstrate how the
      Quantitative Insights Into Microbial Ecology version 2 (QIIME2) software suite
      can simplify 16S rRNA marker-gene analysis. We walk through an example data set
      extracted from the guts of bumblebees in order to show how QIIME2 can transform
      raw sequences into taxonomic bar plots, phylogenetic trees, principal co
      ordinates analyses, and other visualizations of microbial diversity.

PMID- 30298252
TI  - Processing a 16S rRNA Sequencing Dataset with the Microbiome Helper Workflow.
AB  - Sequencing microbiome samples has recently become a fast and cost-effective
      method to taxonomically profile communities. The growing interest in analyzing
      microbial sequencing data has attracted many new researchers to the field. Here,
      we present a straightforward bioinformatic pipeline that aims to streamline the
      processing of 16S rRNA sequencing data. This workflow is part of the larger
      project called Microbiome Helper (Comeau et al. mSyst 2:e00127-16, 2017), which
      includes other bioinformatic workflows, tutorials, and scripts available here:
      https://github.com/mlangill/microbiome_helper/wiki .

PMID- 30298253
TI  - Normalization of Microbiome Profiling Data.
AB  - Normalization is a term that is often used but rarely defined and poorly
      understood. The number of choices of normalization procedure is large-some are
      inappropriate or inadmissible-and all are narrowly relevant to a specific
      analysis that depends on both the nature of the data and the question being
      asked. This chapter describes key definitions of normalization as they apply in
      metagenomics, mainly for taxonomic profiling data; while also demonstrating
      specific, reproducible examples of normalization procedures in the context of
      analysis techniques for which they were intended. The analysis and graphics code
      is distributed as a supplemental companion to this chapter so that the motivated
      reader can re-use it on new data.

PMID- 30298254
TI  - Predicting the Functional Potential of the Microbiome from Marker Genes Using
      PICRUSt.
AB  - Marker-gene sequencing is a cost-effective method of taxonomically profiling
      microbial communities. Unlike metagenomic approaches, marker-gene sequencing does
      not provide direct information about the functional genes that are present in the
      genomes of community members. However, by capitalizing on the rapid growth in the
      number of sequenced genomes, it is possible to infer which functions are likely
      associated with a marker gene based on its sequence similarity with a reference
      genome. The PICRUSt tool is based on this idea and can predict functional
      category abundances based on an input marker gene. In brief, this method requires
      a reference phylogeny with tips corresponding to taxa with reference genomes as
      well as taxa lacking sequenced genomes. A modified ancestral state reconstruction
      (ASR) method is then used to infer counts of functional categories for taxa
      without reference genomes. The predictions are written to pre-calculated files,
      which can be cross-referenced with other datasets to quickly generate predictions
      of functional potential for a community. This chapter will give an in-depth
      description of these methods and describe how PICRUSt should be used.

PMID- 30298255
TI  - Metagenome Assembly and Contig Assignment.
AB  - The recent development of metagenomic assembly has revolutionized metagenomic
      data analysis, thanks to the improvement of sequencing techniques, more powerful
      computational infrastructure and the development of novel algorithms and methods.
      Using longer assembled contigs rather than raw reads improves the process of
      metagenomic binning and annotation significantly, ultimately resulting in a
      deeper understanding of the microbial dynamics of the metagenomic samples being
      analyzed. In this chapter, we demonstrate a typical metagenomic analysis pipeline
      including raw read quality evaluation and trimming, assembly and contig binning.
      Alternative tools that can be used for each step are also discussed.

PMID- 30298256
TI  - From RNA-seq to Biological Inference: Using Compositional Data Analysis in Meta
      Transcriptomics.
AB  - The proper analysis of high-throughput sequencing datasets of mixed microbial
      communities (meta-transcriptomics) is substantially more complex than for
      datasets composed of single organisms. Adapting commonly used RNA-seq methods to
      the analysis of meta-transcriptome datasets can be misleading and not use all the
      available information in a consistent manner. However, meta-transcriptomic
      experiments can be investigated in a principled manner using Bayesian
      probabilistic modeling of the data at a functional level coupled with analysis
      under a compositional data analysis paradigm. We present a worked example for the
      differential functional evaluation of mixed-species microbial communities
      obtained from human clinical samples that were sequenced on an Illumina platform.
      We demonstrate methods to functionally map reads directly, conduct a
      compositionally appropriate exploratory data analysis, evaluate differential
      relative abundance, and finally identify compositionally associated (constant
      ratio) functions. Using these approaches we have found that meta-transcriptomic
      functional analyses are highly reproducible and convey significant information
      regarding the ecosystem.

PMID- 30298257
TI  - Subsampled Assemblies and Hybrid Nucleotide Composition/Differential Coverage
      Binning for Genome-Resolved Metagenomics.
AB  - Metagenomic analyses for reconstruction of genomes from mixed microbial community
      datasets now routinely allow rapid, accurate genome recovery for tens to hundreds
      of organisms from environmental samples. This chapter provides a step-by-step
      protocol for reconstructing genomes from metagenomic datasets, with a focus on
      the most abundant community members. Subsampling assembly approaches are
      implemented to improve assembly of abundant genome sequences, an iterative
      process that targets progressively less abundant populations and improves total
      community representation in the final merged assembly. A hybrid approach to
      genome binning is described, combining differential coverage information from a
      series of metagenomic samples with nucleotide composition information. This
      approach strengthens binning through application of multiple independent
      variables for contig clustering. Genome curation through error correction and gap
      closure leads to high-quality draft genomes, and, for some community members,
      closed and complete genome sequences reconstructed directly from environmental
      samples.

PMID- 30298258
TI  - Transkingdom Networks: A Systems Biology Approach to Identify Causal Members of
      Host-Microbiota Interactions.
AB  - Improvements in sequencing technologies and reduced experimental costs have
      resulted in a vast number of studies generating high-throughput data. Although
      the number of methods to analyze these "omics" data has also increased,
      computational complexity and lack of documentation hinder researchers from
      analyzing their high-throughput data to its true potential. In this chapter we
      detail our data-driven, transkingdom network (TransNet) analysis protocol to
      integrate and interrogate multi-omics data. This systems biology approach has
      allowed us to successfully identify important causal relationships between
      different taxonomic kingdoms (e.g., mammals and microbes) using diverse types of
      data.

PMID- 30298259
TI  - Constructing and Analyzing Microbiome Networks in R.
AB  - Microbiomes are complex microbial communities whose structure and function are
      heavily influenced by microbe-microbe and microbe-host interactions mediated by a
      range of mechanisms, all of which have been implicated in the modulation of
      disease progression and clinical outcome. Therefore, understanding the microbiome
      as a whole, including both the complex interplay among microbial taxa and
      interactions with their hosts, is essential for understanding the spectrum of
      roles played by microbiomes in host health, development, dysbiosis, and
      polymicrobial infections. Network theory, in the form of systems-oriented, graph
      theoretical approaches, is an exciting holistic methodology that can facilitate
      microbiome analysis and enhance our understanding of the complex ecological and
      evolutionary processes involved. Using network theory, one can model and analyze
      a microbiome and all its complex interactions in a single network. Here, we
      describe in detail and step by step, the process of building, analyzing and
      visualizing microbiome networks from operational taxonomic unit (OTU) tables in R
      and RStudio, using several different approaches and extensively commented code
      snippets.

PMID- 30298260
TI  - Bayesian Inference of Microbial Community Structure from Metagenomic Data Using
      BioMiCo.
AB  - Microbial samples taken from an environment often represent mixtures of
      communities, where each community is composed of overlapping assemblages of
      species. Such data represent a serious analytical challenge, as the community
      structures will be present as complex mixtures, there will be very large numbers
      of component species, and the species abundance will often be sparse over
      samples. The structure and complexity of these samples will vary according to
      both biotic and abiotic factors, and classical methods of data analysis will have
      a limited value in this setting. A novel Bayesian modeling framework, called
      BioMiCo, was developed to meet this challenge. BioMiCo takes abundance data
      derived from environmental DNA, and models each sample by a two-level mixture,
      where environmental OTUs contribute community structures, and those structures
      are related to the known biotic and abiotic features of each sample. The model is
      constrained by Dirichlet priors, which induces compact structures, minimizes
      variance, and maximizes model interpretability. BioMiCo is trained on a portion
      of the data, and once trained a BioMiCo model can be employed to make predictions
      about the features of new samples. This chapter provides a set of protocols that
      illustrate the application of BioMiCo to real inference problems. Each protocol
      is designed around the analysis of a real dataset, which was carefully chosen to
      illustrate specific aspects of real data analysis. With these protocols, users of
      BioMiCo will be able to undertake basic research into the properties of complex
      microbial systems, as well as develop predictive models for applied microbiomics.

PMID- 30298261
TI  - Analyzing Metabolic Pathways in Microbiomes.
AB  - Understanding the metabolic activity of a microbial community, at both the level
      of the individual microbe and the whole microbiome, provides fundamental
      biological, biochemical, and clinical insights into the nature of the microbial
      community and interactions with their hosts in health and disease. Here, we
      discuss a method to examine the expression of metabolic pathways in microbial
      communities using data from metatranscriptomic next-generation sequencing data.
      The methodology described here encompasses enzyme function annotation,
      differential enzyme expression and pathway enrichment analyses, and visualization
      of metabolic networks with differential enzyme expression levels.

PMID- 30298262
TI  - Sparse Treatment-Effect Model for Taxon Identification with High-Dimensional
      Metagenomic Data.
AB  - To identify disease-associated taxa is an important task in metagenomics. To
      date, many methods have been proposed for feature selection and prediction.
      However, those proposed methods are either using univariate (generalized)
      regression approaches to get the corresponding P-values without considering the
      interactions among taxa, or using lasso or L0 type sparse modeling approaches to
      identify taxa with best predictions without providing P-values. To the best of
      our knowledge, there are no available methods that consider taxon interactions
      and also generate P-values.In this paper, we propose a treatment-effect model for
      identifying taxa (STEMIT) and performing statistical inference with high
      dimensional metagenomic data. STEMIT will provide a P-value for a taxon through a
      two-step treatment-effect maximization. It will provide causal inference if the
      study is a clinical trial. We first identify taxa associated with the treatment
      effect variable and the targeting feature with sparse modeling, and then estimate
      the P-value of the targeting gene with ordinary least square (OLS) regression. We
      demonstrate that the proposed method is efficient and can identify biologically
      important taxa with a real metagenomic data set. The software for L0 sparse
      modeling can be downloaded at https://cran.r-project.org/web/packages/l0ara/ .

PMID- 30298263
TI  - Semantic memories prime autobiographical memories: General implications and
      implications for everyday autobiographical remembering.
AB  - This study investigated the idea that semantic memory activation causes the
      activation of associated autobiographical memories (e.g., reading the word summer
      activates knowledge representations in semantic memory, as well as associated
      personal memories about summer in autobiographical memory). We tested this
      semantic-autobiographical memory priming hypothesis in three experiments. In
      Experiment 1, participants were primed with concepts (e.g., summer) on a
      familiarity task and were then given a word-cue voluntary autobiographical memory
      task. In support of the hypothesis, the results showed that primed participants
      had more autobiographical memories overlapping with the primed concepts than
      control participants. In Experiment 2, participants were similarly primed, but in
      this case they were given a measure of involuntary autobiographical memory (i.e.,
      Schlagman and Kvavilashvili's (Memory & Cognition, 36, 920-932, 2008) vigilance
      task). The results of this experiment also supported the semantic
      autobiographical memory-priming hypothesis. Experiment 3 ruled out an alternative
      possibility (i.e., that autobiographical memory processing had occurred in the
      word familiarity task) by showing that semantic-autobiographical priming had
      resulted from a priming task (lexical decision) where autobiographical memory
      processing was unlikely. The implications of these findings are discussed.

PMID- 30298264
TI  - The Tool for the Automatic Analysis of Cohesion 2.0: Integrating semantic
      similarity and text overlap.
AB  - This article introduces the second version of the Tool for the Automatic Analysis
      of Cohesion (TAACO 2.0). Like its predecessor, TAACO 2.0 is a freely available
      text analysis tool that works on the Windows, Mac, and Linux operating systems;
      is housed on a user's hard drive; is easy to use; and allows for batch processing
      of text files. TAACO 2.0 includes all the original indices reported for TAACO
      1.0, but it adds a number of new indices related to local and global cohesion at
      the semantic level, reported by latent semantic analysis, latent Dirichlet
      allocation, and word2vec. The tool also includes a source overlap feature, which
      calculates lexical and semantic overlap between a source and a response text
      (i.e., cohesion between the two texts based measures of text relatedness). In the
      first study in this article, we examined the effects that cohesion features,
      prompt, essay elaboration, and enhanced cohesion had on expert ratings of text
      coherence, finding that global semantic similarity as reported by word2vec was an
      important predictor of coherence ratings. A second study was conducted to examine
      the source and response indices. In this study we examined whether source overlap
      between the speaking samples found in the TOEFL-iBT integrated speaking tasks and
      the responses produced by test-takers was predictive of human ratings of speaking
      proficiency. The results indicated that the percentage of keywords found in both
      the source and response and the similarity between the source document and the
      response, as reported by word2vec, were significant predictors of speaking
      quality. Combined, these findings help validate the new indices reported for
      TAACO 2.0.

PMID- 30298265
TI  - The "Small World of Words" English word association norms for over 12,000 cue
      words.
AB  - Word associations have been used widely in psychology, but the validity of their
      application strongly depends on the number of cues included in the study and the
      extent to which they probe all associations known by an individual. In this work,
      we address both issues by introducing a new English word association dataset. We
      describe the collection of word associations for over 12,000 cue words, currently
      the largest such English-language resource in the world. Our procedure allowed
      subjects to provide multiple responses for each cue, which permits us to measure
      weak associations. We evaluate the utility of the dataset in several different
      contexts, including lexical decision and semantic categorization. We also show
      that measures based on a mechanism of spreading activation derived from this new
      resource are highly predictive of direct judgments of similarity. Finally, a
      comparison with existing English word association sets further highlights
      systematic improvements provided through these new norms.

PMID- 30298266
TI  - Quantification of nonverbal synchrony using linear time series analysis methods:
      Lack of convergent validity and evidence for facets of synchrony.
AB  - Nonverbal synchrony describes coordination of the nonverbal behavior of two
      interacting partners. Additionally, it seems to be important in human
      interactions, such as during psychotherapy. Currently, there are several options
      for the automated determination of synchrony based on linear time series analysis
      methods (TSAMs). However, investigations into whether the different methods
      measure the same construct have been missing. In this study, N = 84 patient
      therapist dyads were videotaped during psychotherapy sessions. Motion energy
      analysis was used to assess body movements. We applied seven different TSAMs and
      recorded multiple output scores (average synchrony, maximum synchrony, and
      frequency of synchrony; in total, N = 16 scores). Convergent validity was
      examined using correlations of the output scores and exploratory factor analysis.
      Additionally, two criterion-based validations were conducted: investigations of
      concordant validity with a more generalized nonlinear method, and of the
      predictive validity of the synchrony scores for improvement in interpersonal
      problems at the end of therapy. We found that the synchrony measures only
      partially correlated with each other. The factor analysis did not support a
      common-factor model. A three-factor model with a second-order synchrony variable
      showed the best fit for eight of the selected synchrony scores. Only some
      synchrony scores were able to predict improvement at the end of therapy. We
      concluded that the considered TSAMs do not measure the same synchrony construct,
      but different facets of synchrony: the strength of synchrony of the total
      interaction, the strength of synchrony during synchronization intervals, and the
      frequency of synchrony.

PMID- 30298267
TI  - Interpersonal Stress Severity Longitudinally Predicts Adolescent Girls'
      Depressive Symptoms: the Moderating Role of Subjective and HPA Axis Stress
      Responses.
AB  - In recent decades, stress response models of adolescent depression have gained
      attention, but it remains unclear why only certain adolescents are vulnerable to
      the depressogenic effects of stress while others are not. Building on evidence
      that affective and physiological responses to stress moderate the impact of
      stress exposure on depression, the current study examined whether the interaction
      between severity of interpersonal stress, subjective affective reactivity, and
      hypothalamic-pituitary-adrenal (HPA) axis reactivity to an acute, in-vivo
      psychosocial stressor prospectively predicted depressive symptoms nine months
      later. Hypotheses were examined with a clinically-oversampled group of 182
      adolescent girls (aged 12-16) to ensure an examination of the widest possible
      range of risk. Self-report measures of affect and salivary cortisol samples were
      collected before and after an in-vivo stress task to assess affective reactivity
      and HPA axis reactivity, respectively. Severity of interpersonal stress between
      baseline and nine months was assessed using a semi-structured interview and was
      objectively coded for severity and content theme (i.e., interpersonal vs. non
      interpersonal). Results indicate that experiences of severe interpersonally
      themed stress predict elevated levels of depressive symptoms longitudinally only
      for adolescent girls with elevated affective reactivity to stress, and suggest
      that these deleterious effects of stress are most exacerbated for girls with
      elevated physiological responses to stress. Findings suggest that it may be
      critical to examine both affective and physiological stress responses when
      assessing risk for depression in adolescents.

PMID- 30298268
TI  - Erratum to: Modified neck-lengthening osteotomy after Morscher in children and
      adolescents.
AB  - Erratum to:Oper Orthop Traumatol 2018 https://doi.org/10.1007/s00064-018-0561-9
      The article was wrongly published under the article type "Review". Please note
      that the article is an "Original Paper".The publisher apologizes to authors and
      readers.

PMID- 30298269
TI  - Budd-Chiari syndrome: a focussed and collaborative approach.

PMID- 30298271
TI  - [Positioning of external pelvic stabilization devices in patients with multiple
      injuries : Retrospective computed tomographic evaluation].
AB  - BACKGROUND: Severe hemorrhage is a dreaded complication of pelvic fractures. It
      has a significant impact on early trauma-associated mortality. Hemorrhage that is
      secondary to pelvic fractures can be reduced by external stabilization devices.
      Despite the commercial availability of many different systems, they are
      infrequently used. The aim of this computed tomography (CT) study was to examine
      the use of external pelvic stabilization devices. METHODS: Between 1 January 2011
      and 31 December 2015 a total of 982 images produced in CT trauma scans at a level
      1 trauma centre were retrospectively examined with respect to the presence of
      external pelvic stabilizers. The type of device applied, its actual position
      including deviation from optimal position as well as pelvic parameters and
      complications were determined. RESULTS: In 67 out of 982 patients (6.82%) with
      suspected multiple trauma, an external pelvic stabilizer was employed. In 41.8%
      the devices were not placed in concordance with prevailing scientific knowledge,
      53.73% of devices did not comply with the manufacturer's instructions and 51.85%
      of systems with pneumatic cuffs caused significant malrotation. In one patient
      the cuff induced hypoperfusion of the leg but without further sequelae.
      CONCLUSION: While the prehospital use of pelvic slings is increasing,
      misplacement is very common. Especially inconsistencies between manufacturers'
      manuals and current scientific knowledge warrant further improvement. In systems
      with pneumatic cuffs malrotation of the device is common and clinically relevant.
      Hypoperfusion of the lower extremities is possible and should be taken into
      account when employing these devices.

PMID- 30298270
TI  - [Delirium in intensive care patients : A multiprofessional challenge].
AB  - Delirium is the most common form of cerebral dysfunction in intensive care
      patients and is a medical emergency that must be avoided or promptly diagnosed
      and treated. According to current knowledge the development of delirium seems to
      be caused by an interplay between increased vulnerability (predisposition) and
      simultaneous exposure to delirogenic factors. Since delirium is often overlooked
      in the clinical routine, a continuous screening for delirium should be performed.
      Due to the close connection between delirium, agitation and pain, sedation and
      analgesia must be evaluated at least every 8 h analogous to delirium screening.
      According to current knowledge, a multifactorial and multiprofessional approach
      is favored in the prevention and treatment of delirium. Non-pharmaceutical
      interventions through early mobilization, reorientation, sleep improvement,
      adequate pain therapy and avoidance of polypharmacy are of great importance.
      Depending on the clinical picture, different substances are used in symptom
      oriented drug treatment of delirium. In order to achieve these diagnostic and
      therapeutic goals, an interdisciplinary treatment team consisting of intensive
      care, intensive care physicians, ward pharmacists, physiotherapists, nutrition
      specialists and psychiatrists is necessary in order to meet the requirements of
      the patient and their relatives.

PMID- 30298273
TI  - Determination of Formaldehyde in Water Samples by High-Performance Liquid
      Chromatography with Methyl Acetoacetate Derivatization.
AB  - A high-performance liquid chromatography method with methyl acetoacetate
      derivatization via the Hantzsch reaction was developed for the analysis of
      formaldehyde (HCHO) in several water samples. Under optimized conditions, HCHO
      was detected within 4 min and was not affected by excessive derivatization
      reagents. The calibration curve constructed from the peak height of HCHO was
      linear, with a correlation coefficient of 0.9998. The relative standard deviation
      of the peak height from ten replicates was 0.29%. The detection and quantitative
      limits were 0.96 ug/L and 3.16 ug/L, respectively. A recovery test of HCHO was
      performed to compare the developed method with the official analysis method (DNPH
      method). The developed method was used to determine the HCHO levels in several
      water samples (tap water, river water, and waste water).

PMID- 30298272
TI  - Oliguria in critically ill patients: a narrative review.
AB  - Oliguria is often observed in critically ill patients. However, different
      thresholds in urine output (UO) have raised discussion as to the clinical
      importance of a transiently reduced UO of less than 0.5 ml/kg/h lasting for at
      least 6 h. While some studies have demonstrated that isolated oliguria without a
      concomitant increase in serum creatinine is associated with higher mortality
      rates, different underlying pathophysiological mechanisms suggest varied clinical
      importance of reduced UO, as some episodes of oliguria may be fully reversible.
      We aim to explore the clinical relevance of oliguria in critically ill patients
      and propose a clinical pathway for the diagnostic and therapeutic management of
      an oliguric, critically ill patient.

PMID- 30298274
TI  - Perfluoroalkyl Substances in Water from the Yangtze River and Its Tributaries at
      the Dividing Point Between the Middle and Lower Reaches.
AB  - The Yangtze River drainage basins are China's most important economic development
      zones and also the locations of several large-scale fluorine chemical industries.
      In order to reveal the contribution from the tributaries at the dividing point
      between the middle and lower reaches of the Yangtze River with respect to
      perfluorinated substances (PFASs), 17 PFAS compounds in surface water,
      groundwater, and tap water samples were analyzed in the tributary system of the
      Jiujiang section of the Yangtze River. The total concentrations of PFASs in the
      surface waters ranged from 7.8 to 586.2 ng/L. High proportion of short-chain
      compound PFBS in surface waters in Nanchang City, Poyang Lake, and the Yangtze
      River was observed which is likely of WWTPs' origin.

PMID- 30298275
TI  - Integrated Biomarker Responses in Livers of the Pale Chub Zacco platypus for Risk
      Assessment of a Stream Contaminated by Wastewater Effluents.
AB  - We evaluated the effects of wastewater effluents on pale chub (Zacco platypus) in
      a contaminated stream by integrating genotoxic, oxidative stress, histological,
      and physiological biomarkers. The metal pollution index indicated higher
      pollution loads at downstream sites (DS1 and DS2) compared with the upstream
      reference site. Significantly higher nuclear abnormality confirmed the existence
      of genotoxicity (p < 0.05) at downstream sites. Antioxidant activity (catalase
      and glutathione S-transferase) and lipid peroxidation levels in livers of Z.
      platypus were also significantly higher at the DS1 site (p < 0.05). The liver
      somatic index was also influenced, with abnormal histological alterations in the
      liver, possibly caused by heavy metal accumulation (Cd, Co, Cr, Mn, Ni, and Pb).
      The integrated biomarker response value was the highest at DS1 (13.74) followed
      by DS2 (1.94), indicating that wastewater effluents had the potential to cause
      adverse effects on Z. platypus inhabiting receiving stream.

PMID- 30298276
TI  - Is the dual-task cost of walking and texting unique in people with multiple
      sclerosis?
AB  - The objective of the study was to investigate cognitive-motor interference of
      walking while texting in people with multiple sclerosis (PwMS). The study
      included 30 PwMS, mean disease duration 11.8 (SD = 6.8) years, and 15 healthy
      controls. The investigation included a cognitive assessment; texting assessment
      based on 100 typed characters; and gait assessment under two different
      conditions: normal walking and walking while texting. Outcome measures included
      the Symbol Digit Modalities Test to assess cognition. Texting measures included
      accuracy (%) and duration(s). Gait was assessed with axial accelerometers to
      quantify temporal measures. The dual-task cost percentage for the walking tests
      and texting accuracy was determined by calculating the percentage change from a
      single task to a double task. The impact of texting while walking on gait
      measures was significantly higher in PwMS; furthermore, texting was less accurate
      compared to the healthy controls. The dual-task cost for texting accuracy in the
      PwMS group was 153.3 (SD = 105.7) compared to 8.9 (SD = 26.6) in the healthy
      group. A significant association was found solely in the PwMS group between
      cognition and texting accuracy while in a sitting position (R2 = 0.564) and while
      walking (R2 = 0.534). The dual-task cost of walking and texting appears to be
      unique in the MS population.

PMID- 30298277
TI  - Vector competence analysis of two Aedes aegypti lineages from Bello, Colombia,
      reveals that they are affected similarly by dengue-2 virus infection.
AB  - Dengue is the second most prevalent vector-borne disease after malaria in
      Colombia. It is caused by dengue virus, an arbovirus that exhibits high epidemic
      power, which is evidenced by its occurrence in more than 80% of the country,
      largely because of the extensive dispersion of the mosquito vector Aedes aegypti.
      The existence of two lineages of Ae. aegypti has been proposed based on genetic
      differences at the mitochondrial level, and they have been reported to circulate
      in similar proportions in the municipality of Bello (Colombia). It has been
      suggested that the differentiation of these lineages could influence features
      such as vector competence (VC) and life table. With the aim of testing this
      hypothesis, female mosquitoes from both lineages collected from Bello were orally
      challenged with dengue virus serotype 2 (strain D2-HAN) to measure infection,
      dissemination, survival and fecundity. Analysis of VC showed an increase in viral
      titer over time; however, no significant differences were observed between the
      lineages. The survival rate was not different between the infected lineages, but
      comparing lineages, it was lower in infected mosquitoes, which may affect the
      intensity of transmission. Finally, we conclude that the genetic differentiation
      of Ae. aegypti into lineages did not confer differences in epidemiological status
      when the mosquitoes were infected with this D2 serotype strain.

PMID- 30298278
TI  - Pharmacological characterization of the LSD analog N-ethyl-N-cyclopropyl
      lysergamide (ECPLA).
AB  - RATIONALE: The lysergamide lysergic acid diethylamide (LSD) is a prototypical
      classical hallucinogen with remarkably high potency. LSD remains a popular
      recreational drug but is also becoming an important research tool for medical and
      neuroscience studies. Recently, several lysergamides that are close structural
      analogs of LSD have been sold as recreational drugs, which suggests that further
      studies are needed to explore the pharmacological properties of these compounds.
      OBJECTIVE: In this present investigation, another LSD congener, N-ethyl-N
      cyclopropyl lysergamide (ECPLA), which to date has not been marketed as a
      recreational substance, was evaluated for its pharmacological features relative
      to those previously reported for LSD. The experiments focused on interactions
      with the 5-HT2A receptor, which is responsible for mediating the psychedelic
      effects of LSD and other hallucinogens. METHODS: Competitive binding assays were
      performed to measure the affinity of ECPLA for 27 monoamine receptors. The
      ability of ECPLA to activate human 5-HT2 receptor subtypes was assessed using
      calcium mobilization assays. Head twitch response (HTR) studies were conducted in
      C57BL/6J mice to determine whether ECPLA activates 5-HT2A receptors in vivo. Two
      other N-alkyl substituted lysergamides, N-methyl-N-isopropyl lysergamide (MIPLA)
      and N-methyl-N-propyl lysergamide (LAMPA), were also tested in the HTR paradigm
      for comparative purposes. RESULTS: ECPLA has high affinity for most serotonin
      receptors, alpha2-adrenoceptors, and D2-like dopamine receptors. Additionally,
      ECPLA was found to be a potent, highly efficacious 5-HT2A agonist for Gq-mediated
      calcium flux. Treatment with ECPLA induced head twitches in mice with a median
      effective dose (ED50) of 317.2 nmol/kg (IP), which is ~ 40% of the potency
      observed previously for LSD. LAMPA (ED50 = 358.3 nmol/kg) was virtually
      equipotent with ECPLA in the HTR paradigm whereas MIPLA (ED50 = 421.7 nmol/kg)
      was slightly less potent than ECPLA. CONCLUSIONS: These findings demonstrate that
      the pharmacological properties of ECPLA, MIPLA, and LAMPA are reminiscent of LSD
      and other lysergamide hallucinogens.

PMID- 30298279
TI  - Ceritinib for Untreated Anaplastic Lymphoma Kinase-Positive Advanced Non-Small
      Cell Lung Cancer: An Evidence Review Group Evaluation of a NICE Single Technology
      Appraisal.
AB  - The National Institute for Health and Care Excellence (NICE) invited the company
      that manufactures ceritinib (Zykadia(r), Novartis) to submit evidence on the
      clinical and cost effectiveness of the drug, as a first-line treatment for adults
      with anaplastic lymphoma kinase (ALK)-positive (+) advanced non-small-cell lung
      cancer (NSCLC), as part of the Institute's single technology appraisal (STA)
      process. The CRD (Centre for Reviews and Dissemination) and CHE (Centre for
      Health Economics) Technology Assessment Group at the University of York was
      commissioned to act as the Evidence Review Group (ERG). This paper describes the
      Company's submission (CS), the ERG review and NICE's subsequent decisions. The
      evidence submitted in support of ceritinib, as the first-line treatment in ALK+
      advanced NSCLC, was a phase III, international, multicentre, open-label
      randomised controlled trial (RCT) comparing ceritinib with pemetrexed/cisplatin
      plus pemetrexed maintenance therapy (chemotherapy [CT] group). The results
      indicated that ceritinib prolonged progression-free survival (PFS) compared with
      CT. The only comparator considered in the CS was crizotinib. The evidence
      selected in support of crizotinib was PROFILE 1014, an open-label RCT of
      crizotinib, compared with pemetrexed/cisplatin CT (without maintenance therapy),
      in previously untreated advanced or metastatic ALK+ NSCLC. The design and
      population of PROFILE 1014 was similar to that of ASCEND-4, though there were
      some differences between the trials. The Company considered it not possible to
      perform an 'anchor-based' analysis of first-line ceritinib and crizotinib, and
      presented a Matching-Adjusted Indirect Comparison (MAIC) of ceritinib and
      crizotinib using only the ALK inhibitor arm of ASCEND-4 and PROFILE 1014. The
      indirect comparison suggests that ceritinib may be more effective in prolonging
      PFS than crizotinib. The ERG agreed that an indirect comparison using only the
      ALK inhibitor arm of the trials was the only option available in the present
      assessment; however, a number of limitations and potential bias were identified
      in this analysis. The Company's model estimated that ceritinib was cost effective
      when compared with crizotinib. However, the ERG highlighted several concerns with
      the Company's analysis; the ERG's preferred base case estimated an incremental
      cost-effectiveness ratio of L69,255 per quality-adjusted life-year (no patient
      access scheme [PAS] included). The ERG considered the economic analysis to be
      sensitive to changes in assumption used, partly due to the due to the immaturity
      of the overall survival data from trials, which leads to uncertainty around the
      extrapolation used. The NICE Appraisal Committee concluded that ceritinib is
      recommended, within its marketing authorisation, as an option for untreated ALK+
      advanced NSCLC in adults, if the Company provides it with the discount agreed in
      the PAS.

PMID- 30298280
TI  - The Monetary Value of Informal Care: Obtaining Pure Time Valuations Using a
      Discrete Choice Experiment.
AB  - BACKGROUND: Interventions in health care often not only have an effect on
      patients, but also on their informal caregivers. Caregiving can have a profound
      impact on the health and wellbeing of carers. Ignoring these spillovers in
      economic evaluations risks labelling interventions mistakenly as cost-effective,
      at the expense of informal caregivers. OBJECTIVE: This paper investigates
      willingness-to-accept (WTA) values for an hour of informal care, corrected for
      positive and negative impacts of informal care, to facilitate the inclusion of
      informal care hours on the cost side of economic evaluations without double
      counting spillover effects. METHODS: A discrete choice experiment (DCE) was
      conducted among a representative sample of the adult population in the
      Netherlands (n = 552) in September 2011. An experimental design minimizing the D
      error was used to construct choice sets with two unlabelled alternatives with the
      attributes 'hours caregiving', 'monetary compensation for caregiving' and seven
      impacts of caregiving. To operationalize the random utility model, we used a
      panel mixed multinomial logit (MMNL) parameter model. For calculation of WTA, we
      used both population-level parameters and individual-level parameters. RESULTS:
      The mean WTA for an additional hour of informal care, corrected for positive and
      negative impacts of informal care, was ?14.57. The signs of the coefficients were
      all in the expected directions. CONCLUSIONS: This study reports a preference
      based monetary value for informal care, corrected for other impacts. This
      valuation facilitates the inclusion of informal care hours on the cost side in
      economic evaluations without double-counting any spillover effects included on
      the effects side.

PMID- 30298281
TI  - Sustained Elevation of Postoperative Serum Level of Carbohydrate Antigen 19-9 is
      High-Risk Stigmata for Primary Hepatic Recurrence in Patients with Curatively
      Resected Pancreatic Adenocarcinoma.
AB  - BACKGROUND: Survival after surgery for pancreatic adenocarcinoma (PA) is poor and
      heterogeneous, even for curative (R0) resection. Serum carbohydrate antigen (CA)
      19-9 levels are important prognostic markers for resected PA. However, sustained
      elevation of CA19-9 in association with the patterns of recurrence has been
      rarely investigated. METHODS: Patients who underwent R0 resection (n = 539) were
      grouped according to postoperative serum CA19-9 levels (Group E: sustained
      elevation; Group N: no elevation). Clinicopathological factors, patterns of
      recurrence, and survival were compared between the groups. RESULTS: Group E (n =
      159) had significantly shorter median overall survival (17.1 vs. 35.4 months, p <
      0.0001) than Group N (n = 380). Postoperative CA19-9 elevation was a significant
      independent predictor of poor survival in multivariate analysis (hazard ratio
      1.98, p < 0.0001). The rate of hepatic recurrence in Group E was 2.6-fold higher
      than in Group N (45% vs. 17%, p < 0.0001). Postoperative CA19-9 elevation was a
      strongest independent predictor of primary hepatic recurrence (p < 0.0001) by a
      multiple regression model. Loco-regional, peritoneal, and other distant
      recurrence did not differ between the groups. The extent of preoperative CA19-9
      elevation was correlated sustained elevation of CA19-9 after surgery (p < 0.0001)
      and primary hepatic recurrence (p = 0.0019). CONCLUSIONS: Sustained CA19-9
      elevation was strong predictor of primary hepatic recurrence and short survival
      in cases of R0 resection for PA.

PMID- 30298282
TI  - Role of Palliative Resection in Patients with Incurable Advanced Gastric Cancer
      Who are Unfit for Chemotherapy.
AB  - BACKGROUND: The REGATTA trial showed that gastrectomy followed by chemotherapy
      for advanced gastric cancer with a single non-curable factor did not improve
      survival outcomes in comparison with chemotherapy alone. Chemotherapy is
      therefore the mainstay treatment for incurable gastric cancer. However, for
      patients who are unfit for chemotherapy, the role of palliative gastrectomy
      remains controversial. METHODS: We retrospectively identified 207 patients with
      in curable gastric cancer who underwent palliative gastrectomy or bypass surgery
      because of urgent symptoms who were treated from 2002 to 2014. Fifty-nine of
      these patients who did not receive chemotherapy following surgery were enrolled
      in the present study. The patients were divided into the palliative gastrectomy
      group (n = 40) and the bypass surgery group (n = 19). The survival outcomes of
      the two groups were compared. Independent prognostic factors were identified
      using multivariate analysis. RESULTS: The rate of patients who underwent
      gastrectomy was significantly higher among patients whose tumors were located in
      the upper third (n = 19/20, 95%) than in patients whose tumors were located in
      the lower or middle third (n = 21/39, 54%, p = 0.001). The median survival time
      (MST) in the gastrectomy group (145 days) was significantly longer than that in
      the bypass group (86 days) (p = 0.008). Bypass surgery was identified as an
      independent prognostic factor in the multivariate analysis (HR = 2.3; 95%CI = 1.3
      4.2 p = 0.007). CONCLUSIONS: Palliative gastrectomy may improve survival in
      patients with incurable gastric cancer who show emergent symptoms and who are
      unfit for chemotherapy.

PMID- 30298283
TI  - Healthcare Leaders Develop Strategies for Expanding National Surgical, Obstetric,
      and Anaesthesia Plans in WHO AFRO and EMRO Regions.
AB  - BACKGROUND: Worldwide, five billion people lack access to safe, affordable
      surgical, obstetric, and anaesthesia (SOA) care when needed. In many countries, a
      growing commitment to SOA care is culminating in the development of national
      surgical, obstetric, and anaesthesia plans (NSOAPs) that are fully embedded in
      the National Health Strategic Plan. This manuscript highlights the content and
      outputs from a World Health Organization (WHO) lead workshop that supported
      country-led plans for improving SOA care as a component of health system
      strengthening. METHODS: In March 2018, a group of 79 high-level global SOA
      stakeholders from 25 countries in the WHO AFRO and EMRO regions gathered in Dubai
      to provide technical and strategic guidance for the creation and expansion of
      NSOAPs. RESULTS: Drawing on the experience and expertise of represented countries
      that are at different stages of the NSOAP process, topics covered included (1)
      the global burden of surgical, obstetric, and anaesthetic conditions; (2) the key
      principles and components of NSOAP development; (3) the critical evaluation and
      feasibility of different models of NSOAP implementation; and (4) innovative
      financing mechanisms to fund NSOAPs. CONCLUSIONS: Lessons learned include: (1)
      there is unmet need for the establishment of an NSOAP community in order to
      provide technical support, expertise, and mentorship at a regional level; (2)
      data should be used to inform future priorities, for monitoring and evaluation
      and to showcase advances in care following NSOAP implementation; and (3) SOA
      health system strengthening must be uniquely prioritized and not hidden within
      other health strategies.

PMID- 30298284
TI  - A Comparison Between Plastic and Metallic Biliary Stent Placement in Patients
      Receiving Preoperative Neoadjuvant Chemoradiotherapy for Resectable Pancreatic
      Cancer.
AB  - BACKGROUND: The optimal stent type in patients receiving preoperative neoadjuvant
      chemoradiotherapy (NACRT) is uncertain. The present study aimed to compare the
      clinical effectiveness of biliary metallic stent (MS) and plastic stent (PS) in
      patients undergoing preoperative NACRT for resectable pancreatic cancer. METHODS:
      This retrospective study included 43 patients who required either biliary MS or
      PS before initiating NACRT for resectable or borderline resectable pancreatic
      head cancer. Seventeen patients had MS (MS group), while 23 patients had PS (PS
      group). All patients received preoperative NACRT, including gemcitabine and
      concomitant three-dimensional radiation of 54 Gy, and underwent pancreatectomy.
      Stent patency, surgery postponement, postoperative outcomes, and cost
      effectiveness were compared between these groups. RESULTS: There were no
      significant differences in baseline demographic or tumor characteristics between
      the groups. Stent patency was significantly longer in the MS group than in the PS
      group (p = 0.042). There were no differences in time to surgery, intraoperative
      characteristics, surgical complications, margin positivity, and pathological
      response between the groups. Furthermore, the medical cost of maintenance of
      biliary drainage during NACRT was similar between the groups. CONCLUSIONS: MS
      placement compared to PS in patients receiving preoperative NACRT provided no
      significant benefits during the postoperative course of pancreatectomy. However,
      MS placement was associated with long stent patency while showing no economic
      disadvantage. Therefore, MS placement may be recommended in patients receiving
      preoperative NACRT for resectable pancreatic cancer.

PMID- 30298285
TI  - Survival effect of perioperative systemic chemotherapy on overall mortality in
      locally advanced and/or positive regional lymph node non-metastatic urothelial
      carcinoma of the upper urinary tract.
AB  - OBJECTIVES: To analyze the potential survival benefit of perioperative
      chemotherapy (CHT) in patients treated with nephroureterectomy (NU) for non
      metastatic locally advanced upper tract urothelial carcinoma. METHODS: Within the
      Surveillance, Epidemiology, and End Results database (2004-2014), we identified
      1286 patients with T3 or T4, N 0-3 M0 UTUC. Kaplan-Meier plots, as well as
      multivariable Cox regression models (MCRMs) relying on inverse probability after
      treatment weighting (IPTW) and landmark analyses, were used to test the effect of
      CHT vs no CHT on overall mortality (OM) in the overall population (n =1286), as
      well as after stratification according to lymph node invasion (LNI). RESULTS:
      Overall, 37.4% patients received CHT. The CHT rate was higher with LNI (62.2% vs
      35.2%, p < 0.001). In MCRMs, testing for OM in the overall population, CHT was
      associated with lower rates of OM (HR 0.71, CI 0.58-0.87; p = 0.001). Similarly,
      in MCRMs testing for OM in patients with LNI, CHT achieved independent predictor
      status for lower OM (HR 0.61, CI 0.48-0.78; p < 0.001). Conversely, in MCRMs
      testing for OM in patients without LNI, no CHT effect was recorded (HR 0.72, CI
      0.52-1.01; p = 0.05). All results were confirmed after IPTW adjustment and in
      landmark analyses. CONCLUSIONS: Our results represent a contemporary North
      American report indicating lower OM after CHT for patients with locally advanced
      non-metastatic upper tract urothelial carcinoma, specifically in patients with T3
      T4, N1-N3, M0 disease. Validation of the current and of the previous study is
      required within a randomized prospective design.

PMID- 30298286
TI  - Prevalence and surgical management of concurrent adult acquired buried penis and
      urethral stricture disease.
AB  - PURPOSE: To describe the prevalence and surgical management of coexistent adult
      acquired buried penis (AABP) and urethral stricture disease. AABP patients often
      have urinary dribbling with resultant chronic local moisture, infection, and
      inflammation that combine to cause urethral stricture disease. To date, no
      screening or surgical management algorithms have been described. METHODS: A multi
      institutional retrospective study was conducted of the surgical management
      strategies for patients with concurrent AABP and urethral stricture disease from
      2010 to 2017. AABP patient demographics, physical exam findings, and
      comorbidities were compared between those with and without stricture disease to
      suggest those that would selectively benefit from screening for stricture
      disease. RESULTS: Of the 42 patients surgically managed for AABP, 13 had urethral
      stricture disease (31.0%). Stricture location was universal in the anterior
      urethra. Sixty-one percent (n = 8) of strictures were 6 cm or longer and managed
      prior to AABP repair with Kulkarni urethroplasty. Patients with urethral
      stricture disease were significantly more likely to have clinically diagnosed
      lichen sclerosus (p = 0.00019). There was no significant difference in BMI, age,
      or comorbidities between patients with and without urethral stricture disease.
      CONCLUSIONS: Extensive anterior urethral stricture is common in patients with
      AABP. Clinical characteristics cannot predict stricture presence except possibly
      the presence of lichen sclerosus. Definitive stricture surgical options include
      extensive Johanson Urethroplasty or Kulkarni Urethroplasty. Kulkarni
      Urethroplasty prior to AABP repair has the benefits of a single-stage repair,
      good cosmetic outcome with meatal voiding, and dorsal graft placement to allow
      safe degloving of the penis in the subsequent AABP repair.

PMID- 30298287
TI  - The effect of short-term preoperative ureteral stenting on the outcomes of
      retrograde intrarenal surgery for renal stones.
AB  - OBJECTIVES: To evaluate the effect of preoperative ureteral stenting duration on
      the outcomes of retrograde intrarenal surgery (RIRS). PATIENTS AND METHODS: We
      reviewed our database of patients who underwent RIRS between May 2011 and April
      2017 at our institution. The patients were divided into three groups according to
      preoperative ureteral stenting duration: group 1: no stenting, group 2: short
      preoperative stenting (< 7 days) and group 3: long preoperative stenting (>= 7
      days). We compared the rate of ureteral injury, other perioperative
      complications, ureteral dilation and readmission, stone-free rate (SFR) and
      operative time among the groups. RESULTS: A total of 560 patients (215 in group
      1, 177 in group 2 and 168 in group 3) were included in this study. The mean of
      maximum stone size was 13.1 (+/- 6.2) mm, the mean number of stones was 2.3 (+/-
      1.9) and preoperative ureteral stenting duration was 7.2 (+/- 3.7) days. There
      were no significant differences in operative time (75.6, 78.5 and 82.4 min, p =
      0.280), SFR (79.1, 84.2 and 81.0%, p = 0.433), ureteral injury rate (7.0, 5.1 and
      2.4%, p = 0.123) and other perioperative complication rates (12.1, 6.8 and 6.0%,
      p = 0.061). The only one case of grade IV ureteral injury occurred in group 1 and
      the rate of ureteral dilation was significantly higher than in group 2 and 3
      (14.9, 5.7 and 6.0%, p < 0.001). CONCLUSION: Although preoperative ureteral
      stenting duration has no significant effect on operative outcomes, it is an
      effective procedure for reducing the rate of intraoperative ureteral balloon
      dilation and preventing high-grade ureteral injuries.

PMID- 30298288
TI  - A systematic review on global pollution status of particulate matter-associated
      potential toxic elements and health perspectives in urban environment.
AB  - Airborne particulate matter (PM) that is a heterogeneous mixture of particles
      with a variety of chemical components and physical features acts as a potential
      risk to human health. The ability to pose health risk depends upon the size,
      concentration and chemical composition of the suspended particles. Potential
      toxic elements (PTEs) associated with PM have multiple sources of origin, and
      each source has the ability to generate multiple particulate PTEs. In urban
      areas, automobile, industrial emissions, construction and demolition activities
      are the major anthropogenic sources of pollution. Fine particles associated with
      PTEs have the ability to penetrate deep into respiratory system resulting in an
      increasing range of adverse health effects, at ever-lower concentrations. In
      depth investigation of PTEs content and mode of occurrence in PM is important
      from both environmental and pathological point of view. Considering this air
      pollution risk, several studies had addressed the issues related to these
      pollutants in road and street dust, indicating high pollution level than the air
      quality guidelines. Observed from the literature, particulate PTEs pollution can
      lead to respiratory symptoms, cardiovascular problems, lungs cancer, reduced
      lungs function, asthma and severe case mortality. Due to the important role of PM
      and associated PTEs, detailed knowledge of their impacts on human health is of
      key importance.

PMID- 30298289
TI  - Red bone marrow dose estimation using several internal dosimetry models for
      prospective dosimetry-oriented radioiodine therapy.
AB  - The aim of the present study was to review the available models developed for
      calculating red bone marrow dose in radioiodine therapy using clinical data. The
      study includes 18 patients (12 females and six males) with metastatic
      differentiated thyroid cancer. Radioiodine tracer of 73 +/- 16 MBq 131I was
      orally administered, followed by blood sampling (2 ml) and whole-body scans
      (WBSs) done at several time points (2, 6, 24, 48, 72, and >= 96 h). Red bone
      marrow dose was estimated using the OLINDA/EXM 1.0, IDAC-Dose 2.1, and EANM
      models, the models developed by Shen and co-workers, Keizer and co-workers and
      Siegel and co-workers, and Traino and co-workers, as well as the single
      measurement model (SMM). The results were then compared to the standard reference
      model Revised Sgouros Model (RSM) reported by Wessels and co-workers. The mean
      dose deviations of the Traino, Siegel, Shen, Keizer, OLINDA/EXM, EANM, SMM, and
      IDAC-Dose 2.1 models from the RSM were - 17%, - 24%, 6%, - 29%, - 15%, 40%, 48%,
      and - 8%, respectively. The statistical analysis demonstrated no significant
      difference between the results obtained with the RSM and with those obtained with
      the Shen, Traino, OLINDA/EXM, and IDAC-Dose 2.1 models (t test; pvalue > 0.05).
      However, a significant difference was found between RSM doses and those obtained
      with the EANM, SMM, and Keizer models (t test; pvalue < 0.05). The correlation
      between red marrow dose from the SMM and EANM models was modest (R2 = 0.65),
      while the crossfire dose calculated with the OLINDA/EXM and IDAC-Dose 2.1 models
      were in good agreement with each other and with the reference model. The findings
      obtained indicate that most of the dosimetry models can be used for a reliable
      dosimetry, and the calculated total body doses can be considered as a reliable
      non-invasive option for a conservative activity planning. In addition, the
      excellent performance of the IDAC-Dose 2.1 model will be of particular importance
      for a practical and accurate dosimetry, with the advantages of allowing for the
      use of realistic advanced phantoms and updated dose fractions, and of providing
      information about the blood dose contribution to the red bone marrow.

PMID- 30298290
TI  - Disinhibition of the prefrontal cortex leads to brain-wide increases in neuronal
      activation that are modified by spatial learning.
AB  - Deficient prefrontal cortex (PFC) GABA function is hypothesized to play a role in
      schizophrenia and other psychiatric disorders. In rodents, PFC GABAA receptor
      antagonism produces cognitive and behavioral changes relevant to these disorders,
      including impaired spatial memory assessed with the traditional working/reference
      memory radial maze task. This aspect of spatial memory does not depend on PFC,
      suggesting that deficient PFC GABAergic transmission may interfere with non-PFC
      dependent cognitive functions via aberrant increases in PFC output. To test this,
      we assessed whether PFC GABAA antagonism (50 ng bicuculline methbromide) alters
      neuronal activation in PFC terminal regions, including the striatum, thalamus,
      hippocampus, amygdala, and cortical regions, of adult male rats using the
      immediate early gene, c-Fos, as an activity marker. A subset of these animals
      were also trained and/or tested on the working/reference memory radial maze task.
      These treatments caused widespread increases in neuronal activation in animals
      under baseline conditions, with notable exception of the hippocampus.
      Furthermore, PFC GABAA antagonism impaired task performance. In most instances,
      training and/or testing on the radial maze had no additional effects on neuronal
      activation. However, in both the hippocampus and rhomboid thalamic nucleus, PFC
      GABAA antagonism caused a selective increase in neuronal activation in animals
      trained on the maze. These results indicate that deficiencies in PFC GABAergic
      transmission may have widespread impacts on neuronal activity that may interfere
      with certain PFC-independent cognitive functions. Furthermore, these alterations
      in activity are modulated by plasticity induced by spatial learning in the
      hippocampus and rhomboid thalamic nucleus.

PMID- 30298291
TI  - Layer-specific reduced neuronal density in the orbitofrontal cortex of older
      adults with obsessive-compulsive disorder.
AB  - Neurobiological models have provided consistent evidence of the involvement of
      cortical-subcortical circuitry in obsessive-compulsive disorder (OCD). The
      orbitofrontal cortex (OFC), involved in motivation and emotional responses, is an
      important regulatory node within this circuitry. However, OFC abnormalities at
      the cellular level have so far not been studied. To address this question, we
      have recruited a total of seven senior individuals from the Sao Paulo Autopsy
      Services who were diagnosed with OCD after an extensive post-mortem clinical
      evaluation with their next of kin. Patients with cognitive impairment were
      excluded. The OCD cases were age- and sex-matched with 7 control cases and a
      total of 14 formalin-fixed, serially cut, and gallocyanin-stained hemispheres (7
      subjects with OCD and 7 controls) were analyzed stereologically. We estimated
      laminar neuronal density, volume of the anteromedial (AM), medial orbitofrontal
      (MO), and anterolateral (AL) areas of the OFC. We found statistically significant
      layer- and region-specific lower neuron densities in our OCD cases that added to
      a deficit of 25% in AM and AL and to a deficit of 21% in MO, respectively. The
      volumes of the OFC areas were similar between the OCD and control groups. These
      results provide evidence of complex layer and region-specific neuronal
      deficits/loss in old OCD cases which could have a considerable impact on
      information processing within orbitofrontal regions and with afferent and
      efferent targets.

PMID- 30298292
TI  - Ergonomics: making the OR a comfortable place.
AB  - INTRODUCTION: The objective of this video is to highlight strategies to improve
      operating room (OR) ergonomics, which will result in increased surgeon comfort
      during minimally invasive gynecologic surgery and decreased risk of
      musculoskeletal injury. METHODS: Work-related musculoskeletal disorders (WMSDs)
      are prevalent among surgeons, including those who perform minimally invasive
      gynecologic surgery. WMSDs are repetitive strain injuries that can damage a
      surgeon's muscles, nerves, and/or joints and commonly affect the neck, back,
      wrist, and hands. In addition to chronic pain, these injuries can lead to
      decreased job satisfaction and productivity. RESULTS: This video will discuss
      general ergonomic principles and demonstrate ergonomic techniques in conventional
      laparoscopic, vaginal, and robotic surgery. CONCLUSIONS: Minimally invasive
      gynecologic surgery can be physically taxing on the surgeon. Understanding
      principles and utilizing techniques of OR ergonomics can minimize these physical
      demands and result in a long, healthy, and pain-free surgical career.

PMID- 30298295
TI  - Investigation of eye movement pattern parameters of individuals with different
      fluid intelligence.
AB  - Eye movement studies are subject of interest in human cognition. Cortical
      activity and cognitive load impress eye movement influentially. Here, we
      investigated whether fluid intelligence (FI) has any effect on eye movement
      pattern in a comparative visual search (CVS) task. FI of individuals was measured
      using the Cattell test, and participants were divided into three groups: low FI,
      middle FI, and high FI. Eye movements of individuals were then recorded during
      the CVS task. Eye movement patterns were extracted and compared statistically
      among the three groups. Our experiment demonstrated that eye movement patterns
      were significantly different among the three groups. Pearson correlation
      coefficients between FI and eye movement parameters were also calculated to
      assess which of the eye movement parameters were most affected by FI. Our
      findings illustrate that saccade peak velocity had the greatest positive
      correlation with FI score and the ratio of total fixation duration to total
      saccade duration had the greatest negative correlation with FI. Next, we
      extracted 24 features from eye movement patterns and designed: (1) a classifier
      to categorize individuals and (2) a regression analysis to predict the FI score
      of individuals. In the best case examined, the classifier categorized subjects
      with 68.3% accuracy, and the regression predicted FI of individuals with a 0.54
      correlation between observed FI and predicted FI. In our investigation, the
      results have emphasized that imposed loads on low FI individuals is greater than
      that of high FI individuals in the cognitive load tasks.

PMID- 30298293
TI  - Correlations between executive functions and adaptation to incrementally
      increasing sensorimotor discordances.
AB  - A previous study reported that movement directions adapt much better to 60
      degrees  target displacements (double steps) when target displacements are
      introduced incrementally and not abruptly. The present study tested whether
      incremental adaptation to 60 degrees  discordances can be explained by specific
      cognitive abilities. The results showed that an increase of discordance size
      during adaptation enhanced reaction times. Furthermore, the individual
      performance in neuropsychological tests measuring sustained attention, figural
      fluency and perseveration predicted the rate of adaptation at different
      discordance sizes. These results are discussed with reference to recent models on
      directional selectivity and modularity during visually guided reaching.

PMID- 30298294
TI  - Individual preferences in motor coordination seen across the two hands: relations
      to movement stability and optimality.
AB  - The framework of the uncontrolled manifold (UCM) hypothesis was used to explore
      variables related to stability of task performance in the two hands of young
      healthy individuals. Fourteen young adults performed four-finger accurate
      constant force production tasks interrupted by a voluntary quick force pulse
      production and by an externally imposed displacement of all fingers. Three groups
      of variables were used to quantify stability of steady force production: (1)
      indices of the inter-trial variance were computed within the UCM and orthogonal
      to the UCM; (2) indices of motor equivalence were computed between steady-state
      intervals separated by the force pulse and by the finger-lifting episode; and (3)
      referent coordinate and apparent stiffness were computed using the data during
      the ascending phase of the finger-lifting episode. In another task, the subjects
      performed accurate constant force production with visual feedback removal after
      the 8th second, and the drop in the total force after the removal was computed.
      There were differences between the right and left hand in some outcome variables
      such as variance within the UCM, and the timing of anticipatory synergy
      adjustments prior to the force pulse, consistent with the dynamic dominance
      hypothesis. There were significant correlations between the two hands for indices
      that were unrelated to accuracy of performance: variance within the UCM, index of
      motor equivalence, referent coordinate, apparent stiffness, and the drop of total
      force after visual feedback removal. We interpret these findings within the
      concept of stability-optimality trade-off. In particular, we conclude that
      individual subjects select particular, person-specific solutions within the
      spectrum allowed by the explicit task constraints, and this choice is consistent
      between the two hands. We conclude with a hypothesis that selecting specific
      solutions within the stability-optimality trade-off may represent an individual's
      personal preference consistent between the two hands.

PMID- 30298296
TI  - Effect of the selective 5-HT2A receptor antagonist EMD-281,014 on L-DOPA-induced
      abnormal involuntary movements in the 6-OHDA-lesioned rat.
AB  - L-3,4-Dihydroxyphenylalanine (L-DOPA) is the most effective therapy for motor
      symptoms of Parkinson's disease (PD); however, with repeated administration, as
      many as 94% of PD patients develop complications such as L-DOPA-induced
      dyskinesia. We previously demonstrated that EMD-281,014, a highly selective
      serotonin 2A (5-HT2A) receptor antagonist, reduces the severity of dyskinesia in
      the parkinsonian marmoset, without interfering with L-DOPA anti-parkinsonian
      benefit. Here, we assessed the effects of EMD-281,014 on L-DOPA-induced abnormal
      involuntary movements (AIMs) in the 6-hydroxydopamine (6-OHDA)-lesioned rat. We
      first determined the pharmacokinetic profile of EMD-281,014, to administer doses
      leading to clinically relevant plasma levels in the behavioural experiments.
      Dyskinetic 6-OHDA-lesioned rats were then administered EMD-281,014 (0.01, 0.03
      and 0.1 mg/kg) or vehicle in combination with L-DOPA and AIMs severity was
      evaluated. We also assessed the effect of EMD-281,014 on L-DOPA anti-parkinsonian
      action with the cylinder test. We found that the addition of EMD-281,014 (0.01,
      0.03 and 0.1 mg/kg) to L-DOPA did not reduce AIMs severity (P > 0.05), when
      compared to vehicle. EMD-281,014 did not compromise L-DOPA anti-parkinsonian
      action. Our results suggest that the highly selective 5-HT2A receptor antagonist
      EMD-281,014 is well-tolerated by parkinsonian rats, but does not attenuate L-DOPA
      induced AIMs. Our results highlight differences between rodent and primate models
      of PD when it comes to determining the anti-dyskinetic action of 5-HT2A receptor
      antagonists.

PMID- 30298297
TI  - Knockdown of miR-372 Inhibits Nerve Cell Apoptosis Induced by Spinal Cord
      Ischemia/Reperfusion Injury via Enhancing Autophagy by Up-regulating Beclin-1.
AB  - To investigate the role of miR-372/Beclin-1 on nerve cell apoptosis induced by
      spinal cord ischemia/reperfusion injury (SCII). We established in vivo and in
      vitro SCII model. MiR-372 and Beclin-1 expressions in spinal cord tissues of SCII
      rats and SCII nerve cells were measured. The cell apoptosis was detected by flow
      cytometry. MiR-372 inhibitor was used to reduce miR-372 expression. Dual
      luciferase reporter assay was used to confirm the interaction between miR-372 and
      Beclin-1. MiR-372 expression in spinal cord tissues of SCII rats and SCII nerve
      cells was increased, while Beclin-1 expression was decreased. Knockdown of miR
      372 could inhibit SCII nerve cell apoptosis. In addition, MiR-372 could
      negatively regulate Beclin-1 expression. Autophagy inhibitor could inhibit
      autophagy to promote the apoptosis of SCII nerve cells through decreasing Beclin
      1, while interference of miR-372 changed the effect of autophagy inhibitor.
      Interference of miR-372 could reduce nerve cell apoptosis in SCII via increasing
      autophagy by up-regulating Beclin-1.

PMID- 30298298
TI  - Serum Oxidative Stress Marker Levels in Unmedicated and Medicated Patients with
      Schizophrenia.
AB  - Oxidative stress has been suggested to be involved in schizophrenia, but studies
      have demonstrated inconsistent results on oxidative stress marker level/activity
      in patients with schizophrenia. In order to clarify the circulating oxidative
      stress marker level/activity in patients with schizophrenia, this study recruited
      80 schizophrenia patients (40 first-episode, drug-free and 40 chronically
      medicated patients) and 80 controls to analyze serum activities of superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity
      (T-AOC), and levels of lipid peroxidation marker malondialdehyde (MDA) in
      schizophrenia patients, and whether they associate with the severity of the
      disease. We showed that only serum GSH-Px activity was significantly reduced in
      unmedicated patients with schizophrenia when compared with control subjects,
      whereas the other three analyzed oxidative stress markers did not show
      significant differences between cases and controls. Moreover, our results
      demonstrated that chronic medication increased GSH-Px activity and MDA levels in
      patients with schizophrenia, but reduced SOD activity in the patients. We also
      found that short-term antipsychotic treatments on the patients with schizophrenia
      reduced the SOD activity. Correlation analyses indicated that the oxidative
      stress marker activity/level is not significantly associated with the severity of
      schizophrenia, except that SOD level correlated with PANSS positive score
      significantly. Taken together, the data from the present study suggested that the
      dysfunctions of oxidative stress markers in patients with schizophrenia were
      mainly caused by antipsychotics, emphasizing increased oxidative stress as a
      potential side effect of antipsychotics on the patients.

PMID- 30298299
TI  - Versican silencing in BeWo cells and its implication in gestational trophoblastic
      diseases.
AB  - Versican is a proteoglycan known to interact with cells to influence their
      ability to proliferate, differentiate, migrate, invade and assemble extracellular
      matrix, with all of these cell functions present during placentation. In the
      placenta, cytotrophoblast cells have the ability to differentiate into the
      syncytiotrophoblast, a mechanism that is greatly increased in gestational
      trophoblastic diseases (GTD). Nevertheless, the molecular signaling underlying
      the increased syncytiotrophoblast differentiation are still being unveiled and
      may result in novel therapeutic targets for GTD. Versican expression was
      investigated to establish its differential expression among GTD (partial moles,
      complete moles, invasive moles and choriocarcinoma) and the possible functional
      outcomes from versican gene silencing. Tissue samples had their versican
      expression evaluated using immunohistochemistry and RT-PCR. BeWo cells were
      employed for versican silencing with siRNA and the efficiency was confirmed by RT
      PCR, immunofluorescence and flow cytometry. Cell death and forskolin-induced
      syncytialization were analyzed by a morphological analysis and human chorionic
      gonadotropin (hCG) production using immunofluorescence. Versican V0 and V1
      isoforms were mainly expressed in the syncytiotrophoblast and they were the most
      expressed in benign rather than in malignant tumors. BeWo cells also expressed V0
      and V1 isoforms, but only in cells undergoing syncytial fusion. After versican
      silencing, cell death was greatly increased, whereas spontaneous and forskolin
      induced syncytialization decreased as well as hCG production. Versican is
      differentially expressed in GTD and is important for hydatidiform moles
      pathophysiology, protecting trophoblast cells from death and playing a role in
      their differentiation and functionality.

PMID- 30298300
TI  - Low-power laser alters mRNA levels from DNA repair genes in acute lung injury
      induced by sepsis in Wistar rats.
AB  - Acute lung injury (ALI) is defined as respiratory failure syndrome, in which the
      pathogenesis could occur from sepsis making it a life-threatening disease by
      uncontrolled hyperinflammatory responses. A possible treatment for ALI is the use
      of low-power infrared lasers (LPIL), whose therapeutical effects depend on
      wavelength, power, fluence, and emission mode. The evaluation mRNA levels of
      repair gene related to oxidative damage after exposure to LPIL could provide
      important information about the modulation of genes as treatment for ALI. Thus,
      the aim of this study was to evaluate the mRNA levels from OGG1, APEX1, ERCC2,
      and ERCC1 genes in lung tissue from Wistar rats affected by ALI and after
      exposure to LPIL (808 nm; 100 mW). Adult male Wistar rats (n = 30) were
      randomized into six groups (n = 5, for each group): control, 10 J/cm2 (2 J), 20
      J/cm2 (5 J), ALI, ALI + LPIL 10 J/cm2 and ALI + LPIL 20 J/cm2. ALI was induced by
      intraperitoneal E. coli lipopolysaccharide injection (10 mg/kg). Lungs were
      removed, and samples were withdrawn for total RNA extraction, cDNA synthesis, and
      mRNA levels were evaluated by RT-qPCR. Data normality was verified by Kolmogorov
      Smirnov, comparisons among groups were by Student's t test, Mann-Whitney test,
      one-way ANOVA, Kruskal-Wallis followed by post-tests. Data showed that OGG1 (0.39
      +/- 0.10), ERCC2 (0.67 +/- 0.24), and ERCC1 (0.60 +/- 0.19) mRNA levels are
      reduced in ALI group when compared with the control group (1.00 +/- 0.07, 1.03 +/
      0.25, 1.01 +/- 0.16, respectively) and, after LPIL, mRNA relative levels from
      DNA repair genes are altered when compared to non-exposed ALI group. Our research
      shows that ALI alter mRNA levels from genes related to base and nucleotide
      excision repair genes, suggesting that DNA repair is part of cell response to
      sepsis, and that photobiomodulation could modulate the mRNA levels from these
      genes in lung tissue.

PMID- 30298301
TI  - Letter about: nocturnal enuresis in children between laser acupuncture and
      medical treatment-a comparative study.

PMID- 30298302
TI  - Safety and efficacy of immune checkpoint inhibitors for end-stage renal disease
      patients undergoing dialysis: a retrospective case series and literature review.
AB  - Despite the lack of safety and efficacy data regarding immune checkpoint
      inhibitors (ICIs) for renal dysfunction, they have been approved to treat even in
      the patients with end-stage renal disease (ESRD). We report our experience with
      ICI administration to three ESRD patients undergoing hemodialysis. One of the
      patients had a partial response for several months; however, the other patients
      had a stable disease while undergoing dialysis. The toxicity was tolerable;
      however, one patient developed grade 2 pneumonitis. A literature review of other
      rarely reported cases of hemodialysis revealed that 10 out of 13 patients had a
      partial response or complete response; in addition, grade 3 or grade 4 immune
      related adverse events occurred in 3 patients. ESRD combined with dialysis may
      not be a contraindication for the use of ICIs. ICIs can be beneficial to ESRD
      patients undergoing dialysis. However, caution is needed regarding immune-related
      adverse events. Further prospective studies involving pharmacokinetic analyses
      are necessary to obtain reliable safety and efficacy data.

PMID- 30298303
TI  - Phase 1 trial of enzalutamide in combination with gemcitabine and nab-paclitaxel
      for the treatment of advanced pancreatic cancer.
AB  - Background Androgens were shown to play a key role in the growth and progression
      of pancreatic cancer. We evaluated the safety and tolerability of the combination
      of enzalutamide, a novel androgen receptor (AR) antagonist with gemcitabine and
      nab-paclitaxel as a first-line treatment in advanced pancreatic cancer. Methods
      We used the standard 3 + 3 dose escalation design with cohort expansion to
      evaluate 2 dose levels of enzalutamide: 80 mg and 160 mg/day orally (phase 1a) in
      combination with gemcitabine and nab-paclitaxel in metastatic pancreatic cancer
      patients. In the expansion phase (phase 1b), AR+ was a pre-requisite criterion.
      We also evaluated the full pharmacokinetic (PK) profile for nab-paclitaxel and
      enzalutamide. Results We enrolled 24 patients, 12 patients in phase 1a and 12
      patients in phase 1b. The median age was 68 (range, 32-84) years. No DLTs were
      observed. Grade 3/4 treatment related adverse events included neutropenia (44%),
      anemia (40%), leukopenia (24%), nausea and vomiting (20%), diarrhea (16%),
      infections (12%), thrombocytopenia (8%), thromboembolic event (8%), hypertension
      (8%), hypokalemia (8%), hyponatremia (8%), and ALT elevation (8%). Median overall
      survival and progression-free survival was 9.73 [95%CI:9.73-13.5] and 7.53
      (95%CI:6.05-12.8) months, respectively. PK analysis suggests that the combination
      therapy does not impact the kinetics of either drug evaluated. Enzalutamide
      reached steady-state levels between day 22 and 29 and the mean half-life of nab
      paclitaxel was 19.6 +/- 4.7 h. Conclusions Enzalutamide 160 mg daily in
      combination with gemcitabine and nab-paclitaxel can be safely administered with
      no unexpected toxicities. We also noticed preliminary signals of efficacy with
      this combination.

PMID- 30298304
TI  - Effect of a new inhibitor of factor Xa zifaxaban, on thrombosis in the inferior
      vena cava in rabbits.
AB  - In recent years, oral factor Xa inhibitors have become a research focus as
      anticoagulant drugs. Zifaxaban is the first oral FXa inhibitor to enter clinical
      trials in China. The aim of this study was to determine the inhibitory effect of
      zifaxaban on thrombosisthrough a model ofinferior vena cava (IVC) thrombosis in
      rabbits. IVC thrombosis model was established by electrical injury and stenosis,
      and zifaxaban was administered (p.o.) for 5 consecutive days, then coagulation
      indicators and bleeding were observed. The results showed that zifaxaban had
      obvious inhibitory effects on FXa, and had a significant inhibitory effect on IVC
      thrombosis induced by electrical damage and stenosis. The effect of zifaxaban was
      similar to that of rivaroxaban, but the bleeding side-effects of zifaxaban were
      less severe than those of rivaroxaban. Zifaxaban could prolong the prothrombin
      time and activated partial thromboplastin time of plasma similar to that of other
      oral FXa inhibitors. Zifaxaban had a significant inhibitory effect on FXa, but it
      had no obvious effect on other coagulation factors, major anticoagulant factors
      or fibrinolytic indices. Our results suggest that zifaxaban had specific
      inhibitory effects on FXa and inhibited IVC thrombosis in rabbits with its
      hemorrhagic effect was less than that of rivaroxaban. Zifaxaban is ecpected to be
      developed as a new drug for the prevention of deep venous thrombosis, providing
      more medication options for patients with such disease, more research is required
      to support it in the future.

PMID- 30298305
TI  - Direct oral anticoagulants: a review of common medication errors.
AB  - Stroke and venous thromboembolism continues to be a major cause of morbidity and
      mortality worldwide. The use of anticoagulation therapy has proven effective in
      the prevention of stroke and management of thromboembolism; however, initiating
      treatment may bear clinical burden given the capacity of these agents to cause
      bleeding. Originally, warfarin has been primarily used, but with the approval of
      direct oral anticoagulants, therapeutic recommendations have shifted to direct
      oral anticoagulants for first line therapy for venous thromboembolism for
      patients without cancer. As compared to warfarin, direct oral anticoagulants are
      associated with predictable pharmacokinetic profiles, lower bleeding risks, and
      minimal drug interactions. Complexities in the medication use process can however
      heighten the risks of causing adverse events. The purpose of this article is to
      describe common medication errors associated with direct oral anticoagulants,
      provide practical guidance on the management of direct oral anticoagulants, and
      suggest strategies to reduce errors. Efforts to minimize medication errors
      involve the participation of an interdisciplinary team that has standardized
      policies, risk reduction strategies, and guiding principles to achieve optimal
      therapeutic outcomes. Current primary literature is not robust in assessment of
      clinical impact of medication errors associated with DOACs but reports of adverse
      drug events have been noted. Future studies should be guided to assess clinical
      outcomes associated with medication errors and identify potential clinical
      interventions to optimize therapy.

PMID- 30298306
TI  - In reply: Because it's 2018: the need for early career development for female
      anesthesiologists.

PMID- 30298307
TI  - The overexpression of cucumber (Cucumis sativus L.) genes that encode the
      branched-chain amino acid transferase modulate flowering time in Arabidopsis
      thaliana.
AB  - KEY MESSAGE: The overexpression of CsBCATs promotes flowering in Arabidopsis by
      regulating the expression of flowering time genes. The branched-chain amino acid
      transferases (BCATs) play an important role in the metabolism of branched-chain
      amino acids (BCAAs), such as isoleucine, leucine, and valine. They function in
      both the synthesis and the degradation of this class of amino acids. We
      identified and characterized the three BCAT genes in cucumber (Cucumis sativus
      L.). The tissue-specific expression profiling in cucumber plants revealed that
      CsBCAT2 and CsBCAT7 were highly expressed in the reproductive tissues, whereas
      CsBCAT3 expression was highly detected in the vegetative tissues. The subcellular
      localization patterns of three CsBCATs were observed in the mitochondria. The
      functional analyses of CsBCATs showed that CsBCAT2 and CsBCAT3 restored the
      growth of bat1Delta/bat2Delta double knockout yeast (Saccharomyces cerevisiae),
      and CsBCAT3 and CsBCAT7 with different substrate preferences acted in a reverse
      reaction. The transgenic approach demonstrated that the overexpression of the
      three CsBCATs resulted in early flowering phenotypes, which were associated with
      the upregulation of FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF
      CONSTANS1 (SOC1) in a manner in which they were dependent on GIGANTEA
      (GI)/CONSTANS (CO) and SHORT VEGETATIVE PHASE (SVP)/FLOWERING LOCUS C (FLC)
      modules. Our results, which are observed in conjunction, suggest that there is an
      interconnection between BCAT genes that function in BCAA metabolism and the
      flowering time in plants.

PMID- 30298309
TI  - Preventing Future Deaths from Medicines: Responses to Coroners' Concerns in
      England and Wales.
AB  - INTRODUCTION: Coroners inquire into sudden, unexpected, or unnatural deaths. We
      have previously established 99 cases (100 deaths) in England and Wales in which
      medicines or part of the medication process or both were mentioned in coroners'
      'Regulation 28 Reports to Prevent Future Deaths' (coroners' reports). OBJECTIVE:
      We wished to see what responses were made by National Health Service (NHS)
      organizations and others to these 99 coroners' reports. METHODS: Where possible,
      we identified the party or parties to whom these reports were addressed (names
      were occasionally redacted). We then sought responses, either from the UK
      judiciary website or by making requests to the addressee directly or, for NHS and
      government entities, under the Freedom of Information Act 2000. Responses were
      analysed by theme to indicate the steps taken to prevent future deaths. RESULTS:
      We were able to analyse one or more responses to 69/99 cases from 106
      organizations. We analysed 201 separate actions proposed or taken to address the
      160 concerns expressed by coroners. Staff education or training was the most
      common form of action taken (44/201). Some organisations made changes in process
      (24/201) or policy (17/201), and some felt existing policies were sufficient to
      address some concerns (22/201). CONCLUSIONS: Coroners' concerns are often of
      national importance but are not currently shared nationally. Only a minority of
      responses to coroners' reports concerning medicines are in the public domain.
      Processes for auditing responses and assessing their effectiveness are opaque.
      Few of the responses appear to provide robust and generally applicable ways to
      prevent future deaths.

PMID- 30298308
TI  - Metagenomic analysis and the functional profiles of traditional fermented pork
      fat 'sa-um' of Northeast India.
AB  - Fermented pork fat (sa-um) is traditionally and extensively consumed in Northeast
      Indian region for several decades. However, no scientific reports are available
      regarding its nutritional value as well as its potential health risks. The
      objective of this work was essentially the characterization of sa-um using a
      polyphasic approach, viz., physicochemical, electrospray ionization-mass
      spectrometry (ESI+-MS) and metagenomic analysis in order to gain an understanding
      of the nutrient contents and microbial population diversity. On a dry weight
      basis, about 91% fat, 2% carbohydrate and 0.70% protein were present. ESI+-MS
      analysis of sa-um revealed the presence of various polar and neutral lipids
      corresponding to monoacylglyceride, diacylglyceride and triacylglyceride species.
      The dominant bacterial phyla were Firmicutes, Proteobacteria and Bacteroidetes. A
      total of 72 bacterial genera were identified, largely abundant with Clostridium
      species including C. butyricum, C. citroniae, C. methylpentosum, C. perfringens,
      C. saccharogumia and C. tetani. The imputed functional profiles of bacterial
      communities were predominantly involved in energy, carbohydrate and amino acid
      metabolisms. Furthermore, this study deduces the presence of pro-inflammatory
      molecules as well as antibiotic resistance genes associated with the bacterial
      families such as Bacillaceae, Bacteroidaceae, Clostridiaceae, Corynebacteriaceae
      and Enterobacteriaceae which might be a major health concern for the sa-um
      consuming population.

PMID- 30298310
TI  - ASO Author Reflections: Benefit of Adjuvant Radiotherapy for Clinical Outcome in
      Patients with Soft Tissue Sarcoma.

PMID- 30298311
TI  - Multifocal/Multicentric Ipsilateral Invasive Breast Carcinomas with Similar
      Histology: Is Multigene Testing of All Individual Foci Necessary?
AB  - BACKGROUND: Multiple synchronous ipsilateral invasive breast carcinomas (BCs)
      with similar histology usually have concordant receptor status. It is unknown
      whether individual foci with similar histology also share molecular and
      biological similarities or are heterogenous. This study examined the concordance
      of the 21-gene recurrence score (RS) in multiple synchronous morphologically
      similar ipsilateral BCs. PATIENTS AND METHODS: We identified patients with
      multiple ipsilateral BCs and available RS treated at our institution from 1/2014
      to 6/2018. BCs were divided into three groups based on RS: (1) RS in same risk
      category, (2) RS in different risk categories but within 2-unit difference (e.g.,
      RS 17 and RS 19), and (3) RS in different risk categories and a change of > 2
      units. BCs in groups 1 and 2 were considered as concordant (no significant
      clinical impact) and BCs in group 3 as discordant (variation affects management).
      RESULTS: A total of 53 patients met the study criteria. RS was concordant in 46
      (87%) cases. Seven (13%) cases were discordant (group 3). Of these, three (43%,
      3/7) had biopsy cavity changes (BXC) adjacent to the BC with highest RS. In two
      cases the focus with higher RS had a lower percentage of progesterone receptor
      positive tumor cells. In two cases, extensive ductal carcinoma in situ was
      associated with the BC focus with lower RS. CONCLUSIONS: Morphologically similar
      multifocal ipsilateral BCs have concordant RS in 87% (46/53) of cases. Our
      results suggest that, in cases of morphologically similar multifocal BCs, testing
      of a single focus provides accurate prognostic and predictive information.

PMID- 30298312
TI  - ASO Author Reflections: Do Distinct Patterns of Recurrence Impact the Prognosis
      of Patients With Resected Pancreatic Ductal Adenocarcinoma?

PMID- 30298313
TI  - ASO Author Reflections: A Novel Muscle Measure for Gastric Cancer.

PMID- 30298315
TI  - ASO Author Reflections: Palliative Care and Aggressive End-of-Life Care: A
      Surgeon's Reflections on Priorities for the Future.

PMID- 30298314
TI  - Correction to: Phase 2 Open-Label Trial Investigating Percutaneous Laser Ablation
      for Treatment of Early-Stage Breast Cancer: MRI, Pathology, and Outcome
      Correlations.
AB  - The article "Phase 2 Open-Label Trial Investigating Percutaneous Laser Ablation
      for Treatment of Early-Stage Breast Cancer: MRI, Pathology, and Outcome
      Correlations", written by Barbara Schwartzberg et al., was originally published
      electronically on the publisher's internet portal (currently SpringerLink) on
      July 9, 2018, without open access.

PMID- 30298316
TI  - Intraoperative Dexamethasone Decreases Infectious Complications After
      Pancreaticoduodenectomy and is Associated with Long-Term Survival in Pancreatic
      Cancer.
AB  - BACKGROUND: Dexamethasone is administered intraoperatively to prevent anesthesia
      related nausea and vomiting and to reduce postoperative opioid administration.
      However, the adverse effects of corticosteroids on anastomotic healing and wound
      infection as well as oncologic outcomes remain unclear. We analyzed the effect of
      intraoperative dexamethasone administration on surgical outcomes after
      pancreaticoduodenectomy and on long-term survival in pancreatic cancer patients.
      METHODS: A total of 679 pancreaticoduodenectomies from a prospectively maintained
      database were analyzed. Surgical outcomes were compared between patients who
      received intraoperative dexamethasone and those who did not. Kaplan-Meier curves
      and Cox-regression survival analysis were performed in patients with pancreatic
      cancer. A propensity analysis was done to reduce the inherent bias of
      retrospective design. RESULTS: Patients who received dexamethasone (117, 17.2%)
      were younger and more likely to be female than those who did not (p = 0.001).
      Overall and 30-day major morbidity were similar among all resected patients,
      although there were fewer infectious complications in the dexamethasone group
      (18.8% vs. 28.5%, p = 0.032). In pancreatic cancer patients, dexamethasone was
      associated with significantly improved median overall survival (46 vs. 22 months,
      p = 0.017). This effect occurred independently of stage, pathologic
      characteristics, or adjuvant therapy, with adjusted hazard ratios, derived from
      pre-propensity and post-propensity analysis, of 0.67 (0.47-0.97) and 0.57 (0.37
      0.87), respectively. CONCLUSIONS: A single intraoperative dose of dexamethasone
      did not increase morbidity after pancreaticoduodenectomy and, in fact, was
      associated with a decrease in infectious complications. The treatment was
      independently associated with improved overall survival in patients with
      pancreatic adenocarcinoma, an effect that cannot be explained and needs further
      validation in a prospective setting.

PMID- 30298317
TI  - ASO Author Reflections: Survival Trends in Gastric Adenocarcinoma.

PMID- 30298318
TI  - Talimogene Laherparepvec (TVEC) for the Treatment of Advanced Melanoma: A Single
      Institution Experience.
AB  - BACKGROUND: Talimogene laherparepvec (TVEC) is an oncolytic herpes virus used as
      intralesional therapy for patients with unresectable stage IIIB through IV
      melanoma. We reviewed the standard of care treatment of TVEC at a single
      institution. METHODS: All patients treated with TVEC for advanced melanoma were
      retrospectively evaluated from 2015 to 2018. Patient demographics,
      clinicopathologic characteristics, treatment response, and toxicity were
      reviewed. RESULTS: Twenty-seven patients underwent therapy with TVEC. Median age
      was 75 years, and 63% of patients were female. Seventeen (63.0%) patients
      underwent injections on the lower extremity, four (14.8%) on the upper extremity,
      four (14.8%) on the head and neck, and two (7.4%) on the trunk. Median number of
      injections was five. Median follow-up was 8.6 months. Of the 27 patients, 23
      patients met the criteria for response analysis with at least 8 weeks follow-up.
      Ten (43.5%) patients experienced a complete response (CR), three (13.1%)
      experienced a partial response (PR), and five (21.7%) had stable disease (SD) for
      an overall response rate of 56.5% (CR + PR) and a disease control rate of 78.3%
      (CR + PR + SD). Adverse events were mostly limited to mild constitutional
      symptoms within 48 h of injection. Two patients developed cellulitis treated with
      oral antibiotics, and one patient underwent excision of a lesion for ulceration
      and bleeding during therapy. DISCUSSION: TVEC is an effective and well-tolerated
      intralesional therapy for patients with unresectable stage IIIB through IV
      melanoma. A CR was achieved in almost half of patients treated. Disease control
      is seen in the vast majority.

PMID- 30298319
TI  - ASO Author Reflections: Biological Diversity of Histologic Subtypes.

PMID- 30298321
TI  - Outcomes of Non-curative Gastrectomy for Gastric Cancer: An Analysis of the
      American College of Surgeons National Surgical Quality Improvement Program (ACS
      NSQIP).
AB  - BACKGROUND: The surgical care of patients with metastatic gastric cancer (GC)
      remains debated. Despite level 1 evidence showing lack of survival benefit,
      surgery may be used for symptoms prevention or palliation. This study examined
      short-term postoperative outcomes of non-curative gastrectomy performed for
      metastatic GC. METHODS: A multi-institutional retrospective cohort study was
      conducted using the American College of Surgeons National Surgical Quality
      Improvement Program (ACS-NSQIP) registry, including gastrectomies for GC (2007
      2015). The primary outcome was 30-day major morbidity. Multivariable analysis
      examined the association between metastatic status and outcomes adjusted for
      relevant demographic and clinical covariates. RESULTS: Of 5341 patients, 377
      (7.1%) had metastases. Major morbidity was more common with metastases (29.4 vs.
      19.6%; p < 0.001), driven by a higher rate of respiratory events. Prolonged
      hospital length of stay (beyond the 75th percentile: 11 days) was more likely
      with metastases than with no metastases (41.9 vs. 28.3%; p < 0.001). After
      adjustment, metastatic status was associated with major morbidity (odds ratio
      [OR], 1.49; 95% confidence interval [CI], 1.16-1.90). This association remained
      for respiratory events (OR, 1.58; 95% CI, 1.07-2.33), 30-day mortality (OR, 2.19;
      95% CI, 1.38-3.48), and prolonged hospital stay (OR, 1.65; 95% CI, 1.31-2.07).
      CONCLUSION: Non-curative gastrectomy for metastatic GC was associated with
      significant major morbidity and mortality as well as a prolonged hospital stay,
      longer than expected for gastrectomy for non-metastatic GC. These data can inform
      decision making regarding non-curative gastrectomy, helping surgeons to weigh the
      risks of morbidity against the potential benefits and alternative therapeutic
      options.

PMID- 30298322
TI  - ASO Author Reflections: Non-GIST Sarcoma Liver Metastasis: How to Use the Past
      and Present to Predict the Future.

PMID- 30298320
TI  - Influence of Age on the Clinical Outcome of Breast Cancer for Men and the
      Development of Second Primary Cancers.
AB  - BACKGROUND: Low incidence of breast cancer in men (BCM) (< 1% of all breast
      cancers) has led to a paucity of outcome data. This study evaluated the impact of
      age on BCM outcomes. METHODS: For this study, BCM patients treated between 2000
      and 2011 were stratified by age (<= 65 or > 65 years). Kaplan-Meier methods were
      used to compare overall survival (OS) and breast cancer-specific survival (BCSS).
      Competing-risk methods analyzed time to second primary cancers (SPCs), with any
      cause death treated as a competing risk. RESULTS: The study identified 152 BCM
      patients with a median age of 64 years (range 19-96 years). The median body mass
      index (BMI) was 28 kg/m2. Men age 65 years or younger (n = 78, 51%) were more
      overweight/obese than men older than 65 years (n = 74, 49%) (89% vs 74%,
      respectively; P = 0.008). Both groups had similar nodal metastases rates (P =
      0.4), estrogen receptor positivity (P = 1), and human epidermal growth factor
      receptor 2 (HER2)neu overexpression (P = 0.6). Men 65 years of age or younger
      were more likely to receive chemotherapy (P = 0.002). The median follow-up period
      was 5.8 years (range 0.1-14.4 years). The 5-year OS was 86% (95% confidence
      interval [CI] 80-93%), whereas the 5-year BCSS was 95% (95% CI 91-99%). The BCM
      patients 65 years of age and younger had better OS (P = 0.003) but not BCSS (P =
      0.8). The 5-year cumulative incidence of SPC was 8.4% (95% CI 3.4-13.4%). The
      prior SPC rate was higher for men older than 65 years (n = 20, 31%) than for
      those age 65 years or younger (n = 7, 11%) (P = 0.008). This did not account for
      differences in life years at risk. No difference was observed in SPC cumulative
      incidence stratified by age (P = 0.3). CONCLUSIONS: Men 65 years of age or
      younger received more chemotherapy and had improved OS, but not BCSS, compared
      with men older than 65 years. For all BCM, SPC is a risk, and appropriate
      screening may be warranted.

PMID- 30298323
TI  - ASO Author Reflections: A Population-Based Study on Lymph Node Retrieval in
      Patients with Esophageal Cancer.

PMID- 30298324
TI  - ASO Author Reflections: Neoadjuvant Treatment of Resectable and Borderline
      Resectable Pancreatic Head Adenocarcinoma: Is FOLFIRINOX Better than Gem/Nab
      Paclitaxel?

PMID- 30298325
TI  - ASO Author Reflections: Hepatic Artery Infusion (HAI) Chemotherapy is Associated
      with Improved Survival Compared with Radioembolization (Y90) in Patients with
      Isolated Unresectable Colorectal Liver Metastases.

PMID- 30298326
TI  - ASO Author Reflections: Immunoinflammatory Prognostics in Cancer.

PMID- 30298327
TI  - ASO Author Reflections: Optimizing the Outcomes for Patients: The Evolution of
      the Management of Regional Disease in Patients with Melanoma.

PMID- 30298328
TI  - ASO Author Reflections: The Evolution of Minimally Invasive Liver Surgery and the
      Future with Robotics.

PMID- 30298329
TI  - ASO Author Reflections: Towards Better Metrics for Judging Academic Productivity
      in Surgical Oncology.

PMID- 30298330
TI  - ASO Author Reflections: Incorporating Lymphovascular Invasion to Improve the
      Prognostic Reliability of the T-Staging System for Adrenocortical Carcinoma-A
      Multicenter Study.

PMID- 30298331
TI  - Association Between Very Small Tumor Size and Decreased Overall Survival in Node
      Positive Pancreatic Cancer.
AB  - BACKGROUND: In pancreatic adenocarcinoma (PDAC), increasing tumor size usually
      correlates with a worse prognosis. However, patients with a very small primary
      tumor who experience lymph node involvement may have a different disease biology.
      This study sought to determine the interaction between tumor size and lymph node
      involvement in terms of overall survival (OS). METHODS: The study identified
      17,073 patients with a diagnosis of M0 resected PDAC between 1983 and 2013 using
      the Surveillance, Epidemiology, and End Results database. The patients were
      stratified by lymph node involvement (N0 vs N+) and T stage (T1a-T1b vs T1c vs T2
      vs T3 vs T4). The Kaplan-Meier method was used to estimate OS, and Cox regression
      analysis was used to compare survival between subgroups after adjustment for
      patient-specific factors. RESULTS: Lymph node involvement and T stage
      significantly interacted (p < 0.001). Among the patients with node-negative
      disease, 5-year OS decreased monotonically with increasing T stage (59.1%, 30.6%,
      22.9%, 16.6%, and 8.0%, respectively; p < 0.001). In contrast, among the patients
      with node-positive disease, those with T1a-T1b tumors (< 10 mm) had worse 5-year
      OS than those with T1c tumors (7.4% vs 17.6%; adjusted hazard ratio, 0.70; 95%
      confidence interval, 0.50-0.97; p = 0.034) and similar survival compared with
      those who had T2, T3, or T4 tumors (9.7%, 8.2%, and 4.8%, respectively; p > 0.2
      in all cases). CONCLUSIONS: Among patients with lymph node-positive PDAC, very
      small primary tumors are associated with decreased OS. This finding raises the
      possibility that small tumors capable of lymph node metastasis might represent
      more biologically aggressive cancers.

PMID- 30298332
TI  - Lifespan Development: Symptoms Experienced by Individuals with Neurofibromatosis
      Type 1 Associated Plexiform Neurofibromas from Childhood into Adulthood.
AB  - This secondary data analysis qualitatively identified salient concerns reported
      by individuals with Neurofibromatosis Type 1 (NF1)-associated plexiform
      neurofibromas (pNFs) at different stages of development. Past literature has
      focused on overall symptomatology, but has not examined nuances in how these
      symptoms are experienced across developmental phases. Therefore, we aimed to
      identify commonalities and differences in symptom experiences across age groups
      to better assist individuals to adjust to symptoms across the lifespan. Thirty
      one children, adolescents, and adults (age >= 5 years old) and 15 parents
      participated in semi-structured interviews. Analyses focused on the following
      symptom categories: pain, social functioning, physical function impact, and
      stigma. Aspects of pain endorsed by all age groups included localized brief pain
      on contact with pNF and abnormal sensations; however, only adolescents and adults
      reported chronic pain and change in pain over time. Social functioning themes of
      limited activity participation, role limitations, and relationship impact were
      endorsed by all age groups, but differences emerged across age groups in the
      types of activity and role limitations, the type of relationship impact, and
      family planning concerns. All age groups described difficulty with mobility, but
      only parents reported problems with coordination and physical developmental
      milestones. While all age groups reported external stigma, internalized stigma
      was predominately endorsed by adults. While individuals in all age groups
      described pNF concerns related to pain, social function, physical function, and
      stigma, specific aspects of these symptoms differed across the developmental
      continuum. These findings can help assist individuals with pNF better transition
      to the next developmental phases.

PMID- 30298333
TI  - [Digitalization and artificial intelligence in orthopedics and traumatology].
AB  - In the course of digitalization it is becoming increasingly rare for medical
      documents to be handwritten. As a result, digitalization has already become an
      integral part of routine patient care but in contrast to other specialist
      disciplines, such as radiology or laboratory medicine, orthopedics and trauma
      surgery are still at the beginning of new technologies. Artificial intelligence
      is not only used in the form of surgical robots in joint surgery or in the design
      of individualized implants but also provides valuable decision-making aids
      through appropriate algorithms for diagnosis and treatment. It can be assumed
      that these technologies will be further developed and used increasingly more in
      the coming years. Typical examples are intuitively operable and autonomously
      working programs and systems that support the networking and work of medical
      personnel and make processes inside and outside inpatient care more precise and
      less vulnerable to disturbances.

PMID- 30298334
TI  - Neurocritical Care Has Matured and it is Time to Raise the Bar...Yet Again.

PMID- 30298335
TI  - The Timing of Tracheostomy and Outcomes After Aneurysmal Subarachnoid Hemorrhage:
      A Nationwide Inpatient Sample Analysis.
AB  - BACKGROUND: The goal of this study was to investigate the association of
      tracheostomy timing with outcomes after aneurysmal subarachnoid hemorrhage (SAH)
      in a national population. METHODS: Poor-grade aneurysmal SAH patients were
      extracted from the Nationwide Inpatient Sample (2002-2011). Multivariable linear
      regression was used to analyze predictors of tracheostomy timing and
      multivariable logistic regression was used to evaluate the association of timing
      of intervention with mortality, complications, and discharge to institutional
      care. Covariates included patient demographics, comorbidities, severity of
      subarachnoid hemorrhage (measured using the NIS-SAH severity scale), hospital
      characteristics, and other complications and length of stay. RESULTS: The median
      time to tracheostomy among 1380 poor-grade SAH admissions was 11 (interquartile
      range: 7-15) days after intubation. The mean number of days from intubation to
      tracheostomy in SAH patients at the hospital (p < 0.001) was the strongest
      predictor of tracheostomy timing for a patient, while comorbidities and SAH
      severity were not significant predictors. Mortality, neurologic complications,
      and discharge disposition did not differ significantly by tracheostomy time.
      However, later tracheostomy (when evaluated continuously) was associated with
      greater odds of pulmonary complications (p = 0.004), venous thromboembolism (p =
      0.04), and pneumonia (p = 0.02), as well as a longer hospitalization (p < 0.001).
      Subgroup analysis only found these associations between tracheostomy timing and
      medical complications in patients with moderately poor grade (NIS-SAH severity
      scale 7-9), while there were no significant differences by timing of intervention
      in very poor-grade patients (NIS-SAH severity scale > 9). CONCLUSIONS: In this
      analysis of a large, national data set, variation in hospital practices was the
      strongest predictor of tracheostomy timing for an individual. In patients with
      moderately poor grade, later tracheostomy was independently associated with
      pulmonary complications, venous thromboembolism, pneumonia, and a longer
      hospitalization, but not with mortality, neurological complications, or discharge
      disposition. However, tracheostomy timing was not significantly associated with
      outcomes in very poor-grade patients.

PMID- 30298336
TI  - Effects of Osmotic Therapy on Pupil Reactivity: Quantification Using Pupillometry
      in Critically Ill Neurologic Patients.
AB  - BACKGROUND: Osmotic therapy is a critical component of medical management for
      cerebral edema. While up to 90% of neurointensivists report using these
      treatments, few quantitative clinical measurements guide optimal timing, dose, or
      administration frequency. Its use is frequently triggered by a qualitative
      assessment of neurologic deterioration and/or pupil size, and anecdotally appears
      to improve pupil asymmetry suggestive of uncal herniation. However, subjective
      pupil assessment has poor reliability, making it difficult to detect or track
      subtle changes. We hypothesized that osmotic therapy reproducibly improves
      quantitative pupil metrics. METHODS: We included patients at two centers who had
      recorded quantitative pupil measurements within 2 h before and after either 20%
      mannitol or 23.4% hypertonic saline in the neurosciences intensive care unit. The
      primary outcome was the Neurologic Pupil Index (NPi), a composite metric ranging
      from 0 to 5 in which > 3 is considered normal. Secondary outcomes included pupil
      size, percent change, constriction and dilation velocity, and latency. Results
      were analyzed with Wilcoxon signed-rank tests, Chi-square and multi-level linear
      regression to control for other edema-reducing interventions. RESULTS: Out of 72
      admissions (403 paired pupil observations), NPi significantly differed within 2 h
      of osmotic therapy when controlling for other commonly used interventions in our
      whole cohort (beta = 0.08, p = 0.0168). The effect was most pronounced (beta =
      0.57) in patients with abnormal NPi prior to intervention (p = 0.0235).
      CONCLUSIONS: Pupil reactivity significantly improves after osmotic therapy in a
      heterogenous critically ill population when controlling for various other
      interventions. Future work is necessary to determine dose-dependent effects and
      clinical utility.

PMID- 30298338
TI  - Abnormal Microvasculature in Laryngectomy Mucosal Margins may be Associated with
      Increased Risk of Fistula.
AB  - Pharyngocutaneous fistula after laryngectomy is common and significantly
      increases the morbidity of the procedure. Intraoperative, objective variables
      that can reliably predict fistula formation would be useful to surgeons deciding
      how to reconstruct the laryngectomy defect. Retrospective chart review of 50
      radiated patients and 10 non-radiated patients who underwent total laryngectomy
      at a single tertiary care institution. Patients with pharyngocutaneous fistula
      were selected to ensure a representative sample were available for comparison.
      All patients had pathology slides available for re-review by a single, blinded
      pathologist. Margins of both radiated (n = 50) and non-radiated (n = 10) larynges
      were examined for 7 histologic features, and odds ratios were calculated to
      assess whether these features were associated with fistula. When evaluating all
      60 patients, both telangiectatic capillaries and hyalinized arterioles were
      associated with fistula (OR 3.72 and 9.21, respectively). Collinearity between
      the variables was evaluated; findings indicated a high likelihood of having
      hyalinized arterioles if telangiectatic capillaries were also present (OR 31.67
      [3.13, 320.06]). Microvascular changes in radiated tissue have previously been
      described in other anatomic subsites, but the larynx and pharynx have not been
      specifically evaluated. Laryngectomy mucosal margins appear to display similar
      changes, and evidence of this damage may be associated with fistula formation.
      These features could potentially guide the surgeon to alter the reconstructive
      technique.

PMID- 30298337
TI  - Medical Image Analysis using Convolutional Neural Networks: A Review.
AB  - The science of solving clinical problems by analyzing images generated in
      clinical practice is known as medical image analysis. The aim is to extract
      information in an affective and efficient manner for improved clinical diagnosis.
      The recent advances in the field of biomedical engineering have made medical
      image analysis one of the top research and development area. One of the reasons
      for this advancement is the application of machine learning techniques for the
      analysis of medical images. Deep learning is successfully used as a tool for
      machine learning, where a neural network is capable of automatically learning
      features. This is in contrast to those methods where traditionally hand crafted
      features are used. The selection and calculation of these features is a
      challenging task. Among deep learning techniques, deep convolutional networks are
      actively used for the purpose of medical image analysis. This includes
      application areas such as segmentation, abnormality detection, disease
      classification, computer aided diagnosis and retrieval. In this study, a
      comprehensive review of the current state-of-the-art in medical image analysis
      using deep convolutional networks is presented. The challenges and potential of
      these techniques are also highlighted.

PMID- 30298339
TI  - Mechanical Stretch of High Magnitude Provokes Axonal Injury, Elongation of
      Paranodal Junctions, and Signaling Alterations in Oligodendrocytes.
AB  - Increasing findings suggest that demyelination may play an important role in the
      pathophysiology of brain injury, but the exact mechanisms underlying such damage
      are not well known. Mechanical tensile strain of brain tissue occurs during
      traumatic brain injury. Several studies have investigated the cellular and
      molecular events following a static tensile strain of physiological magnitude on
      individual cells such as oligodendrocytes. However, the pathobiological impact of
      high-magnitude mechanical strain on oligodendrocytes and myelinated fibers
      remains under investigated. In this study, we reported that an applied mechanical
      tensile strain of 30% on mouse organotypic culture of cerebellar slices induced
      axonal injury and elongation of paranodal junctions, two hallmarks of brain
      trauma. It was also able to activate MAPK-ERK1/2 signaling, a stretch-induced
      responsive pathway. The same tensile strain applied to mouse oligodendrocytes in
      primary culture induced a profound damage to cell morphology, partial cell loss,
      and a decrease of myelin protein expression. The lower tensile strain of 20% also
      caused cell loss and the remaining oligodendrocytes appeared retracted with
      decreased myelin protein expression. Finally, high-magnitude tensile strain
      applied to 158N oligodendroglial cells altered myelin protein expression,
      dampened MAPK-ERK1/2 and MAPK-p38 signaling, and enhanced the production of
      reactive oxygen species. The latter was accompanied by increased protein
      oxidation and an alteration of anti-oxidant defense that was strain magnitude
      dependent. In conclusion, mechanical stretch of high magnitude provokes axonal
      injury with significant alterations in oligodendrocyte biology that could
      initiate demyelination.

PMID- 30298340
TI  - Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
      (ME/CFS).
AB  - A random-sequence peptide microarray can interrogate serum antibodies in a broad,
      unbiased fashion to generate disease-specific immunosignatures. This approach has
      been applied to cancer detection, diagnosis of infections, and interrogation of
      vaccine response. We hypothesized that there is an immunosignature specific to
      ME/CFS and that this could aid in the diagnosis. We studied two subject groups
      meeting the Canadian Consensus Definition of ME/CFS. ME/CFS (n = 25) and matched
      control (n = 25) sera were obtained from a Canadian study. ME/CFS (n = 25) sera
      were obtained from phase 1/2 Norwegian trials (NCT01156909). Sera from six
      healthy controls from the USA were included in the analysis. Canadian cases and
      controls were tested for a disease immunosignature. By combining results from
      unsupervised and supervised analyses, a candidate immunosignature with 654
      peptides was able to differentiate ME/CFS from controls. The immunosignature was
      tested and further refined using the Norwegian and USA samples. This resulted in
      a 256-peptide immunosignature with the ability to separate ME/CFS cases from
      controls in the international data sets. We were able to identify a 256-peptide
      signature that separates ME/CFS samples from healthy controls, suggesting that
      the hit-and-run hypothesis of immune dysfunction merits further investigation. By
      extending testing of both our signature and one previously reported in the
      literature to larger cohorts, and further interrogating the specific peptides we
      and others have identified, we may deepen our understanding of the origins of
      ME/CFS and work towards a clinically meaningful diagnostic biomarker.

PMID- 30298341
TI  - Driveline angle is crucial for preventing driveline infection in patients with
      HeartMate II device.
AB  - We hypothesized that the externalizing direction of the driveline (the driveline
      angle) at the percutaneous exit site would influence the occurrence of driveline
      infection after left ventricular assist device implantation. From August 2013 to
      May 2017, 71 patients were implanted with a HeartMate II device in our center.
      The driveline angle was measured on anteroposterior radiography just after
      implantation. Risk factors for driveline infection were analyzed by uni- and
      multivariate analyses. Driveline infection developed in 10 (14%) patients during
      follow-up. Overall actual freedoms from driveline infection at 6, 12, and 24
      months were 96%, 88%, and 86%, respectively. Overall number of driveline
      infection events per patient-year was 0.16. Receiver operating characteristic
      analysis determined the cut-off point of the driveline angle as 41 degrees . The
      6-, 12-, and 24-month actuarial freedoms from driveline infection in those with
      driveline angle more than 42 degrees  (84%, 74%, and 74%, respectively) were
      significantly lower than in those with driveline angle less than 41 degrees 
      (97%, 94%, and 90%, respectively; p < 0.02). The numbers of driveline infection
      events per patient-year were 0.16 in patients with driveline angle more than 42
      degrees , and 0.04 in patients with driveline angle less than 41 degrees .
      Multivariate analysis demonstrated that driveline angle more than 42 degrees  was
      an independent risk factor for driveline infection (hazard ratio 4.71). Driveline
      angle more than 42 degrees  is an independent risk factor for driveline infection
      in patients with HeartMate II. Externalization of the driveline toward the
      horizontal direction is important to prevent driveline infection with HeartMate
      II.

PMID- 30298342
TI  - Iridescent colouration of male Anna's hummingbird (Calypte anna) caused by
      multilayered barbules.
AB  - The male Anna's hummingbird features a brightly reddish-pink reflecting gorget,
      due to large stacks of melanosomes in the feather barbules, arranged in layers
      separated by keratin. Direct observations together with detailed scatterometry
      demonstrated that the barbules reflect incident light in an approximately
      specular manner. The structural colouration is iridescent, i.e. varies with a
      changing angle of light incidence. Spectrophotometrical measurements of the
      barbule reflectance and absorbance can be well interpreted with calculated
      spectra obtained with a transfer matrix method for optical multilayers, using
      anatomical data and measured refractive index spectra. The organization of the
      reflectors as a Venetian blind presumably functions to create a high spectral
      contrast of the male's plumage during courtship.

PMID- 30298343
TI  - A simple mathematical model using centred loops and random perturbations
      accurately reconstructs search patterns observed in desert ants.
AB  - This paper describes a new mathematical model that is based on centred loops to
      reconstruct the "Systematic Search" behaviour of Cataglyphis desert ants. The
      notable advantage of this model is the combination of simplicity, efficiency and
      performance. All model input is kept to a minimum, using only parameters that
      previous research has shown to be available to the animals at all times: distance
      from the origin, direction of the last step and home vector. Outbound and inbound
      search paths are being combined into loops that return to the origin, sampling
      this area more intensely. A stochastic element is added by random perturbations
      during the next step, mimicking unsystematic errors during the process of path
      integration and yielding the typical search patterns observed in Cataglyphis
      desert ants. The model output is compared to runs observed in the field.

PMID- 30298344
TI  - Metal-Induced Pulmonary Fibrosis.
AB  - PURPOSE OF REVIEW: The incidence of pulmonary fibrosis is increasing worldwide
      and may, in part, be due to occupational and environmental exposures. Secondary
      fibrotic interstitial lung diseases may be mistaken for idiopathic pulmonary
      fibrosis with important implications for both disease management and prognosis.
      The purposes of this review are to shed light on possible underlying causes of
      interstitial pulmonary fibrosis and to encourage dialogue on the importance of
      acquiring a thorough patient history of occupational and environmental exposures.
      RECENT FINDINGS: A recent appreciation for various occupational and environmental
      metals inducing both antigen-specific immune reactions in the lung and
      nonspecific "innate" immune system responses has emerged and with it a growing
      awareness of the potential hazards to the lung caused by low-level metal
      exposures. Advancements in the contrast and quality of high-resolution CT scans
      and identification of histopathological patterns of interstitial pulmonary
      fibrosis have improved clinical diagnostics. Moreover, recent findings indicate
      specific hotspots of pulmonary fibrosis within the USA. Increased prevalence of
      lung disease in these areas appears to be linked to occupational/environmental
      metal exposure and ethnic susceptibility/vulnerability. A systematic overview of
      possible occupational and environmental metals causing interstitial pulmonary
      fibrosis and a detailed evaluation of vulnerable/susceptible populations may
      facilitate a broader understanding of potential underlying causes and highlight
      risks of disease predisposition.

PMID- 30298345
TI  - Parkinsonian Patient with Comorbid Normal Pressure Hydrocephalus : Clinical
      Usefulness of Diagnosis Supported by Neurological Findings.

PMID- 30298346
TI  - European headache federation guideline on idiopathic intracranial hypertension.
AB  - BACKGROUND: Idiopathic Intracranial Hypertension (IIH) is characterized by an
      elevation of intracranial pressure (ICP no identifiable cause. The aetiology
      remains largely unknown, however observations made in a number of recent clinical
      studies are increasing the understanding of the disease and now provide the basis
      for evidence-based treatment strategies. METHODS: The Embase, CDSR, CENTRAL, DARE
      and MEDLINE databases were searched up to 1st June 2018. We analyzed randomized
      controlled trials and systematic reviews that investigate IIH. RESULTS:
      Diagnostic uncertainty, headache morbidity and visual loss are among the highest
      concerns of clinicians and patients in this disease area. Research in this field
      is infrequent due to the rarity of the disease and the lack of understanding of
      the underlying pathology. CONCLUSIONS: This European Headache Federation
      consensus paper provides evidence-based recommendations and practical advice on
      the investigation and management of IIH.

PMID- 30298347
TI  - Refinements in Tear Trough Deformity Correction: Intraoral Release of Tear Trough
      Ligaments: Anatomical Consideration and Clinical Approach.
AB  - BACKGROUND: Correction of tear trough (TT) deformity is a crucial aspect of
      facial rejuvenation. Because the anatomical origins of TT deformity lie in the TT
      ligaments, which firmly attach the dermis to the periosteum, the release of TT
      ligaments should be considered when performing an etiological correction. The aim
      of this paper is to propose an alternative method for TT deformity correction,
      comprising use of filler together with the release of TT ligaments. This
      technique was compared to the procedure of only percutaneous filler. METHODS:
      From January 2014 to December 2015, 10 patients were enrolled in the study for
      recurrence of TT deformity. All the patients underwent TT ligament release and
      filler injections; all had been previously treated with percutaneous hyaluronic
      acid injection without ligament release. Under local anesthesia, the TT ligaments
      were detached using a blunt cannula introduced directly in the supra periosteal
      plane through an intraoral access. Once the ligament was released, the TT
      depression was evenly recontoured with a very small amount of filler. The
      clinical data, digital images, evaluations of outcomes, including patient
      satisfaction rates were collected and compared. RESULTS: Adding the procedure of
      TT ligament release to filler injections showed satisfactory results, avoiding an
      unnatural puffy appearance. The comparison between the two different methods
      showed improved outcomes and increased patient satisfaction with minor patient
      discomfort among those who underwent TT ligament release. CONCLUSION: Because TT
      ligaments are among the etiologic factors of TT deformity, they have a strong
      impact on procedures that are designed to improve TT deformity; therefore, TT
      ligament release should always be considered to obtain satisfactory, natural
      results. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level
      of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 30298348
TI  - Managing Periocular Filler-Related Syndrome Prior to Lower Blepharoplasty.
AB  - BACKGROUND: Hyaluronic acid (HA) fillers are extensively used in periocular
      volume augmentation. Although they have an excellent safety profile, filler
      related issues such as visibility/palpability, contour abnormalities, malar
      edema, and blue-gray dyschromia can occur. Recognition and management of filler
      related issues are critical prior to subsequent procedures. The clinical course
      of patients who had periocular HA filler-related issues and subsequently
      underwent lower eyelid blepharoplasty is described. METHODS: HA filler was
      dissolved with hyaluronidase (15-30 U/cm2) treatment. Visible lower eyelid fat
      prolapse after filler removal was corrected with transconjunctival blepharoplasty
      with fat repositioning and skin resurfacing. Complications and outcome were
      assessed and recorded. RESULTS: Twenty-three patients (46 eyelids) were treated.
      All presented with contour abnormalities, 19 with contour abnormalities and malar
      edema, and seven with blue-gray dyschromia. In 15 patients, one session of
      hyaluronidase completely dissolved the filler, and in eight patients, two
      sessions were required. Of these eight patients, edema resolved after the second
      hyaluronidase injection in four; in the remaining four, mild edema persisted
      despite absence of visible/palpable filler. Postblepharoplasty, 19 patients had
      an acceptable outcome with no complications (82.6%). Four patients had prolonged
      edema postoperatively; three had a resolution by 6 months. In 23 patients who had
      skin resurfacing procedures, there was no incidence of postinflammatory
      hyperpigmentation. CONCLUSIONS: HA filler-related issues need to be identified
      and managed prior to further intervention. Hyaluronidase treatment effectively
      dissolves the filler, but mild malar edema can persist. Outcomes are acceptable
      after subsequent blepharoplasty, but adequate patient counseling is necessary
      about expectations and limitations. LEVEL OF EVIDENCE IV: This journal requires
      that authors assign a level of evidence to each article. For a full description
      of these Evidence-Based Medicine ratings, please refer to the Table of Contents
      or the online Instructions to Authors www.springer.com/00266 .

PMID- 30298349
TI  - A haplotype variant of porcine IFIT2 increases poly(I:C)-induced activation of NF
      kappaB and ISRE-binding factors.
AB  - Interferon-induced protein with tetratricopeptide repeats (IFIT) 2 is associated
      with various viral infections and pathogenesis in humans and mice. However, there
      are few reports on IFIT2 in pigs and the polymorphic information remains unclear.
      Here, by using a direct PCR sequencing method, we identified four single
      nucleotide polymorphisms (SNPs), c.259G>A (p.Gly87Ser), c.520T>G (p.Phe174Val),
      c.571C>T (p.Pro191Ser), and c.879A>G (p.Glu293Glu), for the first time in the
      coding sequence of the porcine (p) IFIT2 gene from a Chinese local breed (Hebao
      pig), Western commercial pig breeds (Yorkshire and Landrace), and a Chinese
      developed breed (Beijing Black pig). SNP c.520T>G (p.Phe174Val) leads to the
      addition of a tetratricopeptide repeat motif, characteristic structure of the
      IFIT family. SNPs c.259G>A and c.520T>G are medium polymorphic loci (0.25 <
      polymorphic information content < 0.5) and distributed differently in Western pig
      breeds and the Chinese local pig, Hebao, which is well known for its strong
      resistance to disease. Additionally, they are completely linked. The four SNPs
      constituted five haplotypes with GTCA and AGCA as dominant. The haplotype variant
      AGCA, which is mainly present in Hebao pigs, significantly synergized the
      poly(I:C)-induced activation of transcription factors, including NF-kappaB and
      IFN-stimulated response element (ISRE)-binding factors, and the expression of
      interferon beta, indicating that the variant contributes to the induction or
      magnitude of the immune response upon viral infection. The data showed that
      variant AGCA might be useful in improving the resistance of pigs to viruses
      through marker-assisted selection.

PMID- 30298352
TI  - Nutrients and non-essential elements in edible crops following long-term mineral
      and compost fertilization of a Mediterranean agricultural soil.
AB  - The effects of long-term soil fertilizations on nutrient and non-essential
      element concentrations in edible parts of three crops important in human diet
      were investigated repeating four treatments (biowaste compost, biowaste compost
      plus mineral nitrogen, mineral NPK, unfertilized control) for seven consecutive
      years (2007-2014). Fruits of Solanum lycopersicum cv San Marzano collected in
      2011 and 2012, bulbs of Allium cepa cv Bianca di Pompei collected in 2012 and
      2013, and bulbs of Foeniculum vulgare cv Orbit collected in 2014 were analyzed.
      Wide variations in element concentrations were observed along time and among
      species, with Ca, K, Mg, and Na higher in fennel bulbs and Cd, Cr, Mn, Ni, Pb,
      and Zn higher in tomato fruits, where Cd reached concentrations up to ninefold
      higher than the permitted values (EU Regulation n. 488/2014). Despite the
      enrichments in soil total Cu and available Cd, Fe, K, Mn, and Zn concentrations
      due to long-term fertilization with biowaste compost (alone or with mineral
      fertilizers), plants showed lower micronutrient and non-essential element
      concentrations in respect to those on unfertilized soils. Considering the
      potential toxicity for human beings of these mobile and persistent elements, the
      obtained findings reassure on the safe use of biowaste compost in agriculture.
      Overall, this study suggests the use of compost as the most advisable
      fertilization practice and highlights the need of multiple crops analysis in
      evaluating the effects of long-term soil fertilization on their chemical
      composition.

PMID- 30298351
TI  - Expression analysis of lncRNA AK370814 involved in the barley vitamin B6 salvage
      pathway under salinity.
AB  - Long non-coding RNAs (lncRNAs), which are longer than > 200 nt, perform various
      functions in a variety of important biological processes. The aim of this study
      is the investigation of relative expression levels of AK372815 putative pyridoxal
      reductase (PLR) gene and sense lncRNA AK370814 on four barley genotypes (Hasat,
      Beysehir 99, Konevi 98 and Tarm 92) in response to 150 mM salinity application
      during 3 days post-germination. Seeds were placed randomly in petri dishes
      containing (a) only H2O (control), (b) 150 mM NaCl, for 72 h. RNA isolation was
      carried out using TriPure(r) reagent from 150 mM salt-treated root and shoot
      samples. Relative expression levels of AK372815 PLR and sense lncRNA AK370814
      were determined by qPCR. Results demonstrated that salinity affected the
      expression levels of both AK372815 PLR gene and sense lncRNA AK370814 during
      germination. Although expression levels of AK372815 PLR tended to be down
      regulated under salinity, expression levels of sense lncRNA AK370814 were up
      regulated. Another goal of this study is improvement of alternative approach to
      NGS technologies for determination of relative expression levels of sense lncRNAs
      under particular circumstances. This is the first report that demonstrates a
      relationship between lncRNA and vitamin B6 salvage pathway.

PMID- 30298350
TI  - Recent research progress of microRNAs in hypertension pathogenesis, with a focus
      on the roles of miRNAs in pulmonary arterial hypertension.
AB  - Hypertension is the most widespread disease in the world affecting humans and
      imparts a significant cardiovascular and renal risk to patients, and extensive
      research over the past few decades has enhanced our understanding of the
      underlying pathogenesis of hypertension. A growing number of studies have shown
      that miRNAs are involved in the pathological mechanisms of hypertension. This
      review summarizes the current understanding of miRNA-mediated modulation of gene
      expression in the hypertension pathogenesis in the past few years. A systematic
      review of PUBMED, EMBASE and SCOPUS was conducted for studies published in the
      past few years. The review covers three topics: miRNAs in pulmonary arterial
      hypertension (PAH), miRNAs and systemic arterial hypertension (SAH), miRNAs and
      application in hypertension. This review summarizes the current understanding of
      miRNA-mediated modulation in the hypertension pathogenesis in the past few years,
      with especially emphasis on miRNAs in PAH. We also discussed the roles of miRNAs
      in SAH, and the therapeutic applications of these miRNAs will be detailed
      discussed in this review. Evidence suggests that miRNAs are involved in the
      pathological mechanisms of hypertension, and the roles of miRNAs in the
      hypertension pathogenesis are confirmed. We need to further investigate the
      regulated roles of miRNAs in the pathogenesis of hypertension and the application
      of miRNAs in the diagnosis and treatment of this disease in the future.

PMID- 30298353
TI  - Date palm ash-MgAl-layered double hydroxide composite: sustainable adsorbent for
      effective removal of methyl orange and eriochrome black-T from aqueous phase.
AB  - Date palm ash (DPA) and MgAl-layered double hydroxide (LDH) composites were
      synthesized by the co-precipitation method and characterized by Fourier transform
      infrared spectroscopy (FTIR), scanning electron microscope (SEM), X-ray
      diffraction (XRD), and Brunauer-Emmett-Teller (BET). The DPA-MgAl-LDH (DPA/MgAl)
      composites were employed for the removal of methyl orange (MO) and eriochrome
      black-T (EBT) from aqueous phase. Incorporation of 33.33% (w/w) DPA into the
      layers of MgAl increased the surface area from 44.46 to 140.65 m2/g, which leads
      to the improved adsorption performance. The maximum adsorption capacity of
      DPA/MgAl (1:2) at 298 K was 242.98 and 425.16 (mg/g) for MO and EBT,
      respectively. The adsorption data of dyes were adequately fitted by a pseudo
      second-order and Langmuir isotherm model. The composite showed excellent
      reusability performance up to three cycles. Addition of DPA into MgAl-LDH
      resulted in an effective low-cost adsorbent for decontamination of dyes from
      wastewater. Graphical abstract ?.

PMID- 30298354
TI  - Characterization of composted sewage sludge during the maturation process: a
      pilot scale study.
AB  - This paper determines the impact of the maturation process of composted sewage
      sludge on the quality of the final product and assesses the stabilization effect.
      The samples of composted sewage sludge were taken from a wastewater treatment
      plant located in Pomerania in northern Poland. The sewage sludge was composted in
      an open windrow composting plant with the addition of straw and wood chips in the
      turning windrow. The aeration of the sewage sludge mixture was conducted based on
      two methods. The first phase (intensive degradation phase of 6 to 8 weeks) was
      characterized by frequently turning; the second phase for maturation used
      aeration channels (2 to 3 months). In three sampling campaigns samples were taken
      from the same windrow after 2 (no. 1), 8 (no. 2), and 12 weeks (no. 3) of
      maturation. Fresh samples were used for analyzing the stabilization parameter as
      static respiration activity (AT4). Furthermore, the values of pH, organic matter
      (OM), total organic carbon (TOC), elementary composition, nutrients, total
      content, and mobile forms of heavy metals were analyzed in the compost samples. A
      significant decrease was found in the stabilization parameter (AT4) during the
      maturation of tested materials. In turn, no significant differences were found in
      the elementary composition. The concentration of most metals increased in the
      final product. The total content of heavy metals in the final product did not
      exceed the limit values for the agricultural use of sewage sludge, compost from
      municipal waste, and for organic fertilizers. There were no significant changes
      in the percentage of bioavailable and mobile forms of heavy metals during compost
      maturation. Zinc was characterized by the highest level of mobile and
      bioavailable forms, which may cause bioaccumulation after the fertilization of
      soil. The study has shown that the process of maturation of compost from sewage
      sludge not affects changes in the content of heavy metal forms. The scope of this
      study has been planned on a wider scale for different variants of sewage sludge
      composting, in order to evaluate the process.

PMID- 30298355
TI  - Selenium (Se) uptake and dynamic changes of Se content in soil-plant systems.
AB  - In this study, we collected crop plants and associated soil samples and
      determined these for selenium (Se) content to analyze the uptake, enrichment, and
      translocation of Se in the different soil-plant systems of an agricultural
      production area, elucidate the dynamic mechanisms relating to Se content in
      plants and soil during different growth periods, and screen plants for high Se
      enrichment ability. Bioconcentration factor determinations indicated that the
      grains of rice have the strongest Se enrichment ability, followed by soybean and
      corn. Translocation factor analysis indicated that the grains of rice and corn
      have similar low translocation abilities for Se compared with soybean. Within the
      study area, the Se content in plants was closely related to the soil available Se
      content and varied considerably among different growth periods and plant organs.
      This study provides a theoretical basis for the development and utilization of
      local agricultural products.

PMID- 30298356
TI  - Evaluation of New Diagnostic Ratios of Naphthalenes and Fluorenes by Identifying
      Severely Weathered Oils Collected in Laboratory Simulations and Coastal
      Weathering Experiments.
AB  - The composition and physical properties of spilled oil have great changes during
      the seriously weathering process. It brings great difficulties to the source
      identification of oil spill. So, the stable and trustworthy diagnostic ratios
      (DRs) for accurate identification of severely weathered spilled oils are very
      important. The explosion of Sinopec pipeline happened on November 22, 2013 at
      Qingdao, China. Local beaches at Jiaozhou Bay were polluted by spilled oils. We
      have collected original spilled oil samples from an area free from human
      interference near the oil leakage point after the accident. Synchronized with
      actual beach weathering, laboratory experiments were conducted to simulate oil
      weathering for 360 days by using the collected original spilled oil samples.
      Based on the t test and the repeatability limit method, 65 DRs of naphthalenes
      and fluorenes were screened. Fifteen DRs, namely, C2Nap/(C2Nap + C3Nap),
      C2Nap/(C2Nap + C4Nap), C2Nap/total Nap, C3Nap/(C3Nap + C4Nap), C3Nap/total Nap,
      C4Nap/total Nap, C2Flu/(C2Flu + C3Flu), C2Flu/total Flu, C2Nap/(C2Nap + Flu),
      C2Nap/(C2Nap + C1Flu), C2Nap/(C2Nap + C2Flu), C2Nap/(C2Nap + C3Flu), C3Nap/(C3Nap
      + Flu),C3Nap/(C3Nap + C1Flu), total Nap/(total Nap + total Flu), have maintained
      remarkable stability during the simulated weathering experiments and field
      weathering process. These stable ratios can retain the characteristics of oil
      source during weathering. They are very beneficial to improve the accuracy of
      identifying the source of severely weathered oil and can be used as an effective
      supplement to existing index system for source identification.

PMID- 30298357
TI  - Measuring facial identity and emotion integration using the redundancy gain
      paradigm.
AB  - Early theories on face perception posit that invariant (i.e., identity) and
      changeable (i.e., expression) facial aspects are processed separately. However,
      many researchers have countered the hypothesis of parallel processes with
      findings of interactions between identity and emotion perception. The majority of
      tasks measuring interactions between identity and emotion employ a selective
      attention design, in which participants are instructed to attend to one dimension
      (e.g., identity) while the other dimension varies orthogonally (e.g., emotion),
      but is task irrelevant. Recently, a divided attention design (i.e., the
      redundancy gain paradigm) in which both identity and emotion are task relevant
      was employed to assess the interaction between identity and emotion. A redundancy
      gain is calculated by a drop in reaction time in trials in which a target from
      both dimensions is present in the stimulus face (e.g., "sad Person A"), compared
      with trials with only a single target present (e.g., "sad" or "Person A").
      Redundancy gains are hypothesized to point to an interactive activation of both
      dimensions, and as such, could complement designs adopting a selective attention
      task. The initial aim of the current study was to reproduce the earlier findings
      with this paradigm on identity and emotion perception (Yankouskaya, Booth, &
      Humphreys, Attention, Perception, & Psychophysics, 74(8), 1692-1711, 2012), but
      our study failed to replicate the results. In a series of subtasks, multiple
      aspects of the design were manipulated separately in our goal to shed light on
      the factors that influence the redundancy gain effect in faces. A redundancy gain
      was eventually obtained after controlling for contingencies and stimulus
      presentation time.

PMID- 30298358
TI  - Expression and function analysis of a rice OsHSP40 gene under salt stress.
AB  - Heat shock proteins (HSPs) play essential roles in both plant growth and abiotic
      stress tolerance. In rice, OsHSP40 was recently reported to regulate programmed
      cell death (PCD) of suspension cells under high temperature. However, the
      expression and functions of OsHSP40 under normal growth or other abiotic stress
      conditions is still unknown. We reported the expression and function of a rice
      OsHSP40 gene under salt stress. Homologous proteins of OsHSP40 were collected
      from the NCBI database and constructed the neighbor-joining (NJ) phylogenetic
      tree. The expression pattern of OsHSP40 was detected by qRT-PCR under NaCl (150
      mM) treatment. Then, identified a rice T-DNA insertion mutant oshsp40. At last,
      we compared and analyzed the phenotypes of oshsp40 and wild type under salt
      stress. OsHSP40 was a constitutively expressed small HSP (sHSP) gene and was
      close related to other plant sHSPs. Moreover, the expression of OsHSP40 was
      regulated by salt, varying across time points and tissues. Furthermore, the
      growth of T-DNA insertion mutant of OsHSP40 (designated as oshsp40) was
      suppressed by NaCl (150 mM) compared with that of the WT at seedling stage.
      Detailed measurement showed root and shoot length of the oshsp40 seedlings were
      significantly shorter than those of the WT seedlings under NaCl stress. In
      addition, the pot experiment results revealed that seedlings of oshsp40 withered
      more seriously compared with those of WT after NaCl treatment and recovery, and
      that survival rate and fresh weight of oshsp40 seedlings were significantly
      reduced. Taken together, these data suggested that OsHSP40 had multiple functions
      in rice normal growth and abiotic stress tolerance.

PMID- 30298359
TI  - Functional evaluation of alternative splicing in the FAM190A gene.
AB  - The human FAM190A gene undergoes frequent alteration in human cancer, most
      commonly involving in-frame deletions in exon 9 or exons 9 & 10. These deletions
      form novel peptide sequences, serving as presumptive cancer-specific neo
      antigens. However, it remains elusive whether these in-frame deletions of FAM190A
      could induce oncogenic properties in vivo. In this study, we aimed to explore the
      functional significance of in-frame deletions in FAM190A genes. We generated two
      deletion mutant forms, FAM190ADeltaexon9 and FAM190ADeltaexon9&10, and examined
      their gain-of-function effects in vitro and in vivo. Global transcript profiling
      in NIH3T3 cells revealed that the transcripts displaying altered expression
      following introduction of FAM190ADeltaexon9 and FAM190ADeltaexon9&10 were
      significantly enriched for genes assigned to cellular movement and cell-to-cell
      signaling, respectively. Furthermore, ectopic expression of FAM190ADeltaexon9 and
      FAM190ADeltaexon9&10 induced in vivo tumor formation in nu/nu mice. Taken
      together, our results are the first to demonstrate the in vivo oncogenic
      properties of in-frame deletions in the FAM190A gene and indicate that these
      transcript variants might be clinically applicable as therapeutic targets in
      patients with cancer.

PMID- 30298360
TI  - Hepatitis C virus cell culture models: an encomium on basic research paving the
      road to therapy development.
AB  - Chronic hepatitis C virus (HCV) infections affect 71 million people worldwide,
      often resulting in severe liver damage. Since 2014 highly efficient therapies
      based on directly acting antivirals (DAAs) are available, offering cure rates of
      almost 100%, if the infection is diagnosed in time. It took more than a decade to
      discover HCV in 1989 and another decade to establish a cell culture model. This
      review provides a personal view on the importance of HCV cell culture models,
      particularly the replicon system, in the process of therapy development, from
      drug screening to understanding of mode of action and resistance, with a special
      emphasis on the contributions of Ralf Bartenschlager's group. It summarizes the
      tremendous efforts of scientists in academia and industry required to achieve
      efficient DAAs, focusing on the main targets, protease, polymerase and NS5A. It
      furthermore underpins the importance of strong basic research laying the ground
      for translational medicine.

PMID- 30298361
TI  - The effect of non-steroidal anti-inflammatory drugs on the osteogenic activity in
      osseointegration: a systematic review.
AB  - Non-steroidal anti-inflammatory drugs are commonly used in implant dentistry for
      management of post-operative pain. The objective of this systematic review was to
      analyse the effect of non-steroidal anti-inflammatory drugs on the osteogenic
      activity of osteoblasts with an emphasis on its effect on osseointegration. A
      systematic literature search for in vitro, animal models, and clinical trials was
      conducted using Ovid, PubMed, Scopus, and Web of Science databases. Articles
      published since the introduction of selective COX-2 inhibitors, between January
      1999 and July 2018, were selected. The integrated search followed the PRISMA
      statement with the following key terms: non-steroidal anti-inflammatory drug/s,
      titanium, osseointegration, and osteoblast. The review is registered at PROSPERO
      database: CRD42016051448. The titles and abstracts of each research article in
      the initial search (n = 875) were independently screened by two reviewers. A
      third independent reviewer reviewed the articles that were included by one but
      excluded by the other reviewer. This resulted in the cataloguing of 79 full-text
      manuscripts where the articles were assessed for the following criteria: the
      study investigates the effects of NSAIDs on osteoblasts, explores the COX pathway
      and its effect on osteogenic activity, and compares the effects of NSAIDs on
      osteoblasts with a control group. A total of 13 articles have been included for
      qualitative synthesis. There is a lack of consensus in the literature to
      explicitly conclude that there is a relationship between the use of post
      operative NSAIDs and failed osseointegration; however, osseointegration does not
      appear to be negatively affected by NSAIDs in the human clinical studies.

PMID- 30298362
TI  - Incidence of Stevens-Johnson syndrome/toxic epidermal necrolysis among new users
      of different individual drugs in a European population: a case-population study.
AB  - PURPOSE: To estimate the specific incidences of Stevens-Johnson syndrome/toxic
      epidermal necrolysis (SJS/TEN) among new users of drugs frequently reported to be
      associated with this serious event. METHODS: We performed a case-population
      approach, which combined data from a registry of SJS/TEN cases from the Madrid
      region (numerator) during the study period 2005-2015 and a primary healthcare
      database from the same catchment population. The proportion of new users of drugs
      estimated in the primary healthcare database was stratified by calendar year, sex
      and age (5-year bands), and then applied to the same strata of Madrid's
      population census to compute the number of new users (denominator). Incidences
      were re-estimated using only cases in which the concerned drug had a probable or
      very probable causal relationship. RESULTS: A total of 44 SJS/TEN cases aged > 14
      years were registered during the study period. The highest SJS/TEN incidence was
      found for phenytoin with 68.9 per 100,000 new users (95% CI 27.7-141.9), followed
      by dexamethasone (5.48; 1.49-14.03), allopurinol (3.29; 1.07-7.67) and
      cotrimoxazole (3.19; 0.87-8.16). Considering only probable and very probable
      cases, the incidences hardly changed, except for dexamethasone, which was left
      without cases. Pantoprazole, levofloxacin and lorazepam showed incidences between
      1 per 100,000 and 1 per 1,000,000 new users. Ibuprofen, amoxicillin-clavulanic
      acid, metamizole, amoxicillin, paracetamol and omeprazole showed incidences
      around 1 per one million new users. CONCLUSIONS: Phenytoin was the drug with the
      highest incidence of SJS/TEN, followed by allopurinol and cotrimoxazole. For the
      rest of the drugs, the estimated incidences were below 1 in 100,000 new users.

PMID- 30298363
TI  - The intact nephron hypothesis as a model for renal drug handling.
AB  - PURPOSE: The intact nephron hypothesis (INH) states that impaired renal function
      results from a reduction in the number of complete (intact) nephrons. Under this
      model, renal drug clearance is assumed to be a linear function of glomerular
      filtration while tubular handling is ignored. The aims of this study were to
      systematically review published studies designed to test the INH and to assess
      the strength of the study designs used. METHODS: A systematic literature search
      was conducted in MEDLINE, EMBASE and Google Scholar. Studies specifically
      designed to understand the relationship between glomerular and tubular function
      across different levels of renal function were included. Studies that found a
      linear relationship between GFR and tubular clearance were deemed to support the
      INH while studies that found a non-linear relationship did not support the INH.
      Study design was accessed using a bespoke strength of evidence score. RESULTS:
      Thirty studies met the criteria for inclusion. Of these, 24 did not support the
      INH. Studies that did not support the INH used methods for measuring tubular
      clearance that were more robust and included subjects with a wider range of GFR
      values than studies that supported the INH. DISCUSSION: Our results suggest that
      the INH may not be a suitable general model for renal drug handling, particularly
      for drugs that are eliminated by tubular mechanisms. Further studies to assess
      the clinical importance of a non-linear relationship between drug clearance and
      GFR are warranted.

PMID- 30298364
TI  - Prevention of venous thrombosis after electrophysiology procedures: a survey of
      national practice.
AB  - PURPOSE: Femoral venous access is required for most electrophysiology procedures.
      Limited data are available regarding post-procedure venous thromboembolism (VTE),
      specifically deep vein thrombosis (DVT) and pulmonary embolism (PE). Potential
      preventative strategies are unclear. We aimed to survey Canadian centers
      regarding incidence of VTE and strategies for prevention of VTE after procedures
      that do not require post-procedure anticoagulation. METHODS: An online survey was
      distributed to electrophysiologists representing major Canadian EP centers.
      Participants responded regarding procedural volume, incidence of VTE post
      procedure, and their practice regarding pharmacological and non-pharmacological
      peri-procedural VTE prophylaxis. RESULTS: The survey included 17 centers that
      performed a total of 6062 procedures in 2016. Ten patients (0.16%) had VTE
      (including 9 DVTs and 6 PEs) after diagnostic electrophysiology studies and right
      sided ablation procedures excluding atrial flutter. Five centers (41.6%)
      administered systemic intravenous heparin during both diagnostic
      electrophysiology studies and right-sided ablation procedures. For patients
      taking oral anticoagulants, 10 centers (58.8%) suspend therapy prior to the
      procedure. Two centers (11.8%) routinely prescribed post-procedure pharmacologic
      prophylaxis for VTE. Four centers (23.5%) used compression dressings post
      procedure and all prescribed bed rest for a maximum of 6 h. Of the variables
      collected in the survey, none were found to be predictive of VTE. CONCLUSIONS:
      VTE is not a common complication of EP procedures. There is significant
      variability in the strategies used to prevent VTE events. Future research is
      required to evaluate strategies to reduce the risk of VTE that may be
      incorporated into EP practice guidelines.

PMID- 30298366
TI  - Letter to the Editor concerning "Predicting medical complications in spine
      surgery: evaluation of a novel online risk calculator" by M. F. Kasparek et al.
      (Eur Spine J: DOI 10.1007/s00586-018-5707-9).

PMID- 30298365
TI  - Long-term survival of patients after ipilimumab and hypofractionated brain
      radiotherapy for brain metastases of malignant melanoma: sequence matters.
AB  - PURPOSE: Since the introduction of ipilimumab (IPI) for the treatment of patients
      with metastatic malignant melanoma, we have observed remarkable responses after
      hypofractionated whole brain irradiation (WBRT) or stereotactic radiotherapy
      (STX) for brain metastases of malignant melanoma. We sought to investigate the
      impact of the sequence of these treatment modalities. METHODS: We retrospectively
      evaluated the survival of melanoma patients with brain metastases who were
      treated with WBRT or STX and received IPI in close temporal relation between
      October 2010 and March 2015. Follow-up was obtained until November 2016. A total
      of 27 patients with advanced melanoma and brain metastases who were treated with
      WBRT before 2010, and who had not received IPI, served as historical controls.
      RESULTS: We identified a total of 41 patients of whom 15 were treated with STX, 7
      with a combination of STX and WBRT and 19 with WBRT alone. All patients received
      at least 2 doses of IPI. The median time interval between radiotherapy and IPI
      was 2 months. Patients treated with IPI after radiotherapy had a censored median
      survival of 11 months, compared with 3 months for the patients who received IPI
      prior to radiotherapy. Patients who received IPI before radiotherapy showed a
      similar survival as historical controls, who had not received IPI. We observed
      long-term survivors after radiotherapy of brain metastases followed by IPI.
      CONCLUSIONS: These data suggest that the sequence of RT and immune checkpoint
      inhibition with IPI may be crucial for the success of combined modality treatment
      of melanoma brain metastases.

PMID- 30298367
TI  - Letter to the Editor concerning "Clinical practice guidelines for the management
      of non-specific low back pain in primary care: an updated overview" by Oliveira
      CB, Maher CG, Pinto RZ, Traeger AC, Lin CWC, Chenot JF, van Tulder M, Koes BW
      (2018) Eur Spine J. https://doi.org/10.1007/s00586-018-5673-2.

PMID- 30298368
TI  - Can regional training courses reduce interobserver variability?
AB  - Cardiovascular disease (CVD) is the principal cause of death worldwide.
      Noninvasive studies have been used for the evaluation of CVD. Ensuring an
      accurate diagnosis of CVD requires well-trained and qualified professionals. IAEA
      has implemented regional training courses which are mainly aimed at professionals
      from countries with less economic development in order to raise their
      professional level so that it is in accordance with international standards and
      thus be able to homogenize the practice of nuclear cardiology globally.

PMID- 30298369
TI  - Low-dose stress-only myocardial perfusion imaging.

PMID- 30298370
TI  - Electrical and mechanical dyssynchrony in patients with right bundle branch
      block.

PMID- 30298371
TI  - Agreement between left ventricular ejection fraction assessed in patients with
      gated IQ-SPECT and conventional imaging.
AB  - BACKGROUND: The aim of the study was to assess the agreement between the left
      ventricular ejection fraction (LVEF) values obtained with IQ-SPECT and those
      obtained with a conventional gamma camera equipped with low-energy high
      resolution (LEHR), considered as the method of reference. METHODS: Gated-stress
      MPI using 99mTc-tetrofosmin was performed in 55 consecutive patients. The
      patients underwent two sequential acquisitions (Method A and B) performed on
      Symbia-IQ SPECT with different acquisition times and one (Method C) on a Ecam
      SPECT equipped with LEHR collimators. The values of the different datasets were
      compared using the Bland-Altman analysis method: the bias and the limits of
      agreement (LA) were estimated in a head-to-head comparison of the three
      protocols. RESULTS: In the (Method A-Method C) comparison for LVEF, the bias was
      3.8% and the LAs ranged from - 9.3% to 16.8%. The agreement was still lower
      between Method B and C, whilst only slightly improved when Methods A and B were
      compared. CONCLUSIONS: The wide amplitude in LA intervals of about 30% indicates
      that IQ and LEHR GSPECT are not interchangeable. The values obtained with IQ
      SPECT should only be used with caution when evaluating the functional state of
      the heart.

PMID- 30298372
TI  - Rubidium-82 positron emission tomography for detection of acute doxorubicin
      induced cardiac effects in lymphoma patients.
AB  - BACKGROUND: Doxorubicin is a cornerstone in lymphoma treatment, but is limited by
      dose-dependent cardiotoxicity. Rubidium-82 positron emission tomography (82Rb
      PET) assesses coronary microvascular function through absolute quantification of
      myocardial perfusion and myocardial perfusion reserve (MPR). Doxorubicin-induced
      microvascular injury represents a potential early marker of cardiotoxicity.
      METHODS AND RESULTS: We included 70 lymphoma patients scheduled for doxorubicin
      based treatment. Cardiotoxicity was evaluated with 82Rb PET myocardial perfusion
      imaging during rest and adenosine stress before chemotherapy and shortly after
      the first doxorubicin exposure. Patients with a MPR decline > 20% were defined as
      having a low threshold for cardiotoxicity. In the 54 patients with complete data
      sets, MPR was significantly lower after the initial doxorubicin exposure (2.69 vs
      2.51, P = .03). We registered a non-significant decline in stress perfusion (3.18
      vs 3.02 ml/g/min, P = .08), but no change in resting myocardial perfusion. There
      were 13 patients with a low cardiotoxic threshold. These patients had a
      significantly higher age, but were otherwise similar to the remaining part of the
      study population. CONCLUSION: Decreases in MPR after initial doxorubicin exposure
      in lymphoma patients may represent an early marker of doxorubicin-induced
      cardiotoxicity. The prognostic value of acute doxorubicin-induced changes in MPR
      remains to be investigated.

PMID- 30298373
TI  - Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and
      Drug-Delivery Characteristics.
AB  - Pentagalloyl glucose (PGG) is an elastin-stabilizing polyphenolic compound that
      has significant biomedical benefits, such as being a free radical sink, an anti
      inflammatory agent, anti-diabetic agent, enzymatic resistant properties, etc.
      This review article focuses on the important benefits of PGG on vascular health,
      including its role in tissue mechanics, the different modes of pharmacological
      administration (e.g., oral, intravenous and endovascular route, intraperitoneal
      route, subcutaneous route, and nanoparticle based delivery and microbubble-based
      delivery), and its potential therapeutic role in vascular diseases such as
      abdominal aortic aneurysms (AAA). In particular, the use of PGG for AAA
      suppression and prevention has been demonstrated to be effective only in the
      calcium chloride rat AAA model. Therefore, in this critical review we address the
      challenges that lie ahead for the clinical translation of PGG as an AAA growth
      suppressor.

PMID- 30298374
TI  - Evaluation of Drug-Loaded Gold Nanoparticle Cytotoxicity as a Function of Tumor
      Vasculature-Induced Tissue Heterogeneity.
AB  - The inherent heterogeneity of tumor tissue presents a major challenge to
      nanoparticle-mediated drug delivery. This heterogeneity spans from the molecular
      (genomic, proteomic, metabolomic) to the cellular (cell types, adhesion,
      migration) and to the tissue (vasculature, extra-cellular matrix) scales. In
      particular, tumor vasculature forms abnormally, inducing proliferative, hypoxic,
      and necrotic tumor tissue regions. As the vasculature is the main conduit for
      nanotherapy transport into tumors, vasculature-induced tissue heterogeneity can
      cause local inadequate delivery and concentration, leading to subpar response.
      Further, hypoxic tissue, although viable, would be immune to the effects of cell
      cycle specific drugs. In order to enable a more systematic evaluation of such
      effects, here we employ computational modeling to study the therapeutic response
      as a function of vasculature-induced tumor tissue heterogeneity. Using data with
      three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated
      interacting with different levels of tissue heterogeneity, and the treatment
      response is measured in terms of tumor regression. The results quantify the
      influence that varying levels of tumor vascular density coupled with the drug
      strength have on nanoparticle uptake and washout, and the associated tissue
      response. The drug strength affects the proportion of proliferating, hypoxic, and
      necrotic tissue fractions, which in turn dynamically affect and are affected by
      the vascular density. Higher drug strengths may be able to achieve stronger tumor
      regression but only if the intra-tumoral vascular density is above a certain
      threshold that affords sufficient transport. This study establishes an initial
      step towards a more systematic methodology to assess the effect of vasculature
      induced tumor tissue heterogeneity on the response to nanotherapy.

PMID- 30298375
TI  - Backbone resonance assignment for the N-terminal region of bacterial tRNA-(N1G37)
      methyltransferase.
AB  - Bacterial tRNA (guanine37-N1)-methyltransferase (TrmD) is an important
      antibacterial target due to its essential role in translation. TrmD has two
      domains connected with a flexible linker. The N-terminal domain (NTD) of TrmD
      contains the S-adenosyl-L-methionine (SAM) cofactor binding site and the C
      terminal domain is critical for tRNA binding. Here we report the backbone NMR
      resonance assignments for NTD of Pseudomonas aeruginosa TrmD. Its secondary
      structure was determined based on the assigned resonances. Relaxation analysis
      revealed that NTD existed as dimers in solution. NTD also exhibited thermal
      stability in solution. Its interactions with SAM and other compounds suggest it
      can be used for evaluating SAM competitive inhibitors by NMR.

PMID- 30298376
TI  - Marinactinospora rubrisoli sp. nov., isolated from red soil.
AB  - A novel Marinactinospora strain JX35-4T was isolated from red soil which was
      collected from Wushan, northern Jiangxi Province, China. Analysis of the 16S rRNA
      gene sequences showed that strain JX35-4T belongs to the genus Marinactinospora
      and formed a distinct phylogenetic clade with Marinactinospora thermotolerans
      SCSIO 00652T and Marinactinospora endophytica YIM 690053T with sequence
      similarity of 96.97% and 96.42%, respectively. The strain was Gram-positive and
      formed branched substrate hyphae with no fragmentation, and abundant aerial
      hyphae that differentiated into long spore chains, and short rod-shaped spores.
      Growth occurred at 20-45  degrees C, pH 7.0-12.0 and in the presence of 0-7.5%
      (w/v) NaCl. The genomic DNA G + C content was determined to be 68.3 mol%. The
      cell wall of strain JX35-4T contained meso-diaminopimelic acid and xylose. Polar
      lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine,
      phosphatidylinositol mannosides and one unidentified phospholipid. The major
      fatty acids of strain JX35-4T consisted of anteiso-C17:0 and iso-C16:0. Major
      menaquinones were MK-9(H10), MK-12 and MK-10(H2). Based on the polyphasic data,
      strain JX35-4T (= CGMCC 4.7382T = DSM 104977T) is concluded to represent a novel
      species of the genus Marinactinospora, for which the name Marinactinospora
      rubrisoli sp. nov. is proposed.

PMID- 30298377
TI  - Usefulness of both PET/CT with F18-FDG and whole-body diffusion-weighted imaging
      in cancer screening: a preliminary report.
AB  - OBJECTIVE: Positron emission tomography/computed tomography (PET/CT) with
      fluorodeoxyglucose (F18-FDG) is useful for the detection of malignant lesions,
      including metastatic lesions, and this technique is widely used in cancer
      screening. However, this approach may occasionally yield false-positive and false
      negative findings. At our PET center, to increase the accuracy of PET/CT, we use
      PET/CT and whole-body diffusion-weighted imaging (WB-DWI) together. This study
      aimed to assess the usefulness of this combination. METHODS: We examined 29
      subjects with confirmed diagnosis. All of them had undergone PET/CT and WB-DWI on
      the same day. Twenty-seven of them also underwent ultrasonography, blood testing,
      and upper gastrointestinal series on the same day and two fecal occult blood
      tests on another day. WB-DWI was performed on a 1.5-T MRI unit with a b value of
      0 and 800 or 1000 s/mm2. For all 29 cases, PET/CT and WB-DWI were classified to
      be positive or negative, and the diagnostic ability was calculated for each
      modality. RESULTS: Among the 29 subjects, 17 had malignant tumors and 12 had
      benign tumors or no abnormalities. The sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT
      were 65%, 25%, 55%, 33%, and 48%, respectively; while the corresponding values
      for WB-DWI were 59%, 100%, 100%, 63%, and 76%, respectively. By considering the
      result to be negative when PET/CT findings were positive but WB-DWI findings were
      negative, specificity increased from 25 to 100%, and accuracy increased from 48
      to 76%. On the other hand, by considering the result to be positive when the
      findings of either PET/CT or WB-DWI were positive, sensitivity increased from 65
      to 76%, and accuracy increased from 48 to 55%. CONCLUSIONS: Our results suggest
      that using both PET/CT and WB-DWI together can increase accuracy in cancer
      screening. However, this approach was not able to detect malignant lesions in
      some cases, indicating that there were limitations with imaging certain organs.
      Therefore, it is important to further understand the features of PET/CT and WB
      DWI and use them appropriately for each organ. Additionally, given that the study
      sample was relatively small, further research is needed to validate these
      findings.

PMID- 30298378
TI  - I-131 as adjuvant treatment for differentiated thyroid carcinoma may cause an
      increase in the incidence of secondary haematological malignancies: an
      "inconvenient" truth?

PMID- 30298379
TI  - Mechanical thromboprophylaxis would suffice after total knee arthroplasties in
      Asian patients?
AB  - PURPOSE: Our prospective study evaluated the incidence and location of deep vein
      thrombosis (DVT), the risk factors for PE and the natural history of DVT after
      TKA in patients who have received only mechanical compression device without
      having any chemical thromboprophylaxis or therapeutic treatment. METHODS: We
      studied 408 consecutive patients (691 knees) who underwent primary TKA; 283
      patients had one-stage bilateral TKAs and 125 had unilateral TKAs. Coagulation
      assays, the full blood count and blood typing tests, and serum chemical profiles
      were undertaken in all patients on three separate occasions. Molecular genetic
      testing was performed preoperatively to detect the genetic traits involving DVT.
      Bilateral simultaneous or unilateral venograms were carried out at 6 or 7 days
      after operation. Perfusion lung scanning was undertaken before and at 7 or 8 days
      after operation. RESULTS: In the 691 venograms in 408 patients, only 4 knees
      (0.6%) were positive for fresh thrombi. In the 4 knees with DVT, thrombi were
      located in the calf veins. We observed factor V Leiden mutation, antithrombin-III
      level, and prothrombin promoter G20210A mutation were absent in all patients. We
      saw no relationship between DVT and coagulation or thrombophilic data. No
      pulmonary embolism (PE) occurred as shown by negative perfusion lung scan and
      absence of symptoms. CONCLUSION: We concluded that the combinations of absent
      thrombophilic polymorphisms with low clinical prothrombotic risk factors led to
      low prevalence of DVT and virtually absent PE after TKA in the current series of
      patients, who had received mechanical compression device only without chemical
      thromboprophylaxis.

PMID- 30298380
TI  - Effects of Thai traditional dance on balance performance in daily life among
      older women.
AB  - BACKGROUND: Previous research indicates that dance training may improve balance
      among older adults. AIMS: This study investigated the effects of Thai traditional
      dance on balance performance among older women. METHODS: Forty-three women aged
      60-80 years, with mean scores between 45 and 52 points on the Berg Balance Scale
      (BBS), were recruited and randomly assigned into two groups: a Thai traditional
      dance group (TTDG) (n = 22) and a control group (CG) (n = 21). TTD program
      comprised three dance sessions of 30-60 min per week over the course of 12 weeks
      while the CG kept their normal daily activities. Balance performance was assessed
      using standardized tests including the NeuroCom Balance Master(r) System (Version
      9.2), the Timed Up and Go Test (TUG) and the BBS. RESULTS: The results revealed
      that overall balance was better for those in TTDG compared to the CG. There was a
      significantly lower sway velocity and faster weight transfer in the Sit-to-Stand
      Test (p <= 0.001) for those in the dance group. TTDG had quicker turn time in the
      Step Quick Turn Test (p <= 0.001), improved Step Up Over Test and Walk Across
      Test, faster movement time, walking speed, and a better score in the TUG after
      training (p <= 0.001). DISCUSSION: A 3-weekly Thai traditional dance intervention
      significantly improved balance and mobility among older community-dwelling women
      as compared to normal daily activities. CONCLUSION: Thai traditional dance could
      potentially prevent age-related mobility and balance decline and its related fall
      risk.

PMID- 30298381
TI  - Radiotherapy in palliation of thoracic tumors: a phase I-II study (SHARON
      project).
AB  - The main clinical goal for patients with advanced or metastatic thoracic cancer
      is palliation of tumor-related symptoms and improvement of quality of life. The
      aim of this phase I-II trial was to define the maximum tolerated dose (MTD) of a
      short-course of palliative radiotherapy (RT) and to evaluate its efficacy in
      terms of palliative response. A phase I trial was planned with escalating dose
      increments. Total doses ranged from 16 to 20 Gy delivered (BID) in two
      consecutive days. Dose limiting toxicity was defined as any acute grade >= 3
      toxicity based on the RTOG scale. MTD was used in the phase II trial to evaluate
      the efficacy of this regimen using a two stage Simon's design. Fifty-four
      patients were enrolled. The upper dose level of 20 Gy was defined as the MTD. In
      patients treated with this dose, the overall palliative response rate was 96.5%
      (CI 0.95: 81.3-99.9%). Complete pain relief rate was 50.0%. Median survival
      without symptomatic progression was 3 months. The tested short course accelerated
      regimen was well tolerated and effective in the palliative setting of metastatic
      or locally advanced chest cancer. A phase III trial is ongoing to validate this
      RT schedule.Trial registration: NCT03465553.

PMID- 30298382
TI  - Longitudinal Kinematic Evaluation of Pharyngeal Swallowing Impairment in
      Thyroidectomy Patients.
AB  - The aim of this study was to assess pharyngeal swallowing impairments in
      thyroidectomy patients and to delineate the contributory kinematic components.
      Forty consecutive patients (mean age = 47.33 years) and fourteen age- and sex
      matched heathy adult volunteers (mean age = 42.64 years) participated in this
      study. A videofluoroscopic swallowing study (VFSS) was performed 1 day prior to
      surgery, and at 1 week and 3 months post-surgery. VFSS images were evaluated
      using the Modified Barium Swallowing Impairment Profile (MBSImp). Kinematic and
      temporal aspects of swallowing were characterized by measurement of maximum hyoid
      and laryngeal excursion, pharyngeal transit duration, laryngeal response duration
      (LRD), and laryngeal closure duration at each three time-points. At 1 week post
      surgery, only pharyngeal impairment was significantly deteriorated than pre
      surgery (p = 0.001). However, at 3 months, a significant improvement was observed
      to pre-surgery level (p = 0.01). Post-surgery, maximum hyoid excursion was
      significantly reduced in patients compared controls (p = 0.001). Although the
      maximal distance of the hyoid and the laryngeal excursion was shorter than before
      surgery, laryngeal excursion at all three time-points was similar to that of
      controls. At all three time-points, LRD was significantly longer in patients than
      in controls (p = 0.01). Following thyroidectomy, pharyngeal aspects of swallowing
      as measured by the MBSImp and kinematic aspects of swallowing were reduced with
      incomplete recovery at 3 months. These exploratory data may guide decision
      regarding management of pharyngeal swallowing impairment with patients undergoing
      total thyroidectomy.

PMID- 30298383
TI  - Repeated KI Prophylaxis in Case of Prolonged Exposure to Iodine Radioisotopes:
      Pharmacokinetic Studies in Adult Rats.
AB  - PURPOSE: To propose a new and effective dose regimen for stable potassium iodide
      (KI) repeated prophylaxis in case of prolonged exposure to radioactive iodine.
      METHODS: The pharmacokinetics of iodine was determined in rats by compartmental
      analyses after intravenous and oral administrations of the optimal dose of 1
      mg/kg KI, which was previously selected in a dose-effect study. The thyroid
      protection against iodine-125 incorporation was followed during 24 h after a
      single oral dosing of KI. A repeated KI prophylaxis was modeled using initial
      estimates of iodine pharmacokinetic parameters. RESULTS: A dose regimen
      consisting in administrations of 1 mg/kg daily for 8 days was selected and
      studied. Plasma iodine concentrations predicted by simulation were verified by
      experimental data and varied after the third dose of KI between 174 and 1190
      MUg/l. The inhibition study of iodine-125 binding in the thyroid as a function of
      the time showed that the protection effect of KI could be correlated to stable
      iodine plasma concentrations. Hence, a theoretical decrease in iodine-125 thyroid
      uptake from 63 to 88% could be achieved in a 24 h-interval between two KI doses.
      CONCLUSION: Given the satisfactory levels of thyroid protection, this dose
      regimen could be envisaged in order to extent KI indications for repeated
      prophylaxis.

PMID- 30298384
TI  - Gonadotropin replacement in male thalassemia major patients with arrested puberty
      and acquired hypogonadotropic hypogonadism (AAH): preliminary results and
      potential factors affecting induction of spermatogenesis.

PMID- 30298385
TI  - The combination of everolimus and terameprocol exerts synergistic
      antiproliferative effects in endometrial cancer: molecular role of insulin-like
      growth factor binding protein 2.
AB  - Oncogenic PIK3CA mutations are common in endometrial cancers, and the
      PI3K/AKT/mTOR pathway is targetable by drugs. We sought to investigate whether
      the combination of an mTOR inhibitor, everolimus (RAD001), and an AKT inhibitor,
      terameprocol (M4N), exerts better antiproliferative effects in endometrial
      cancer. The molecular mechanisms underlying their pharmacological action were
      also examined. The combination of RAD001 and M4N exerted in vitro synergistic
      effects on cell viability, apoptosis, and expression of IGFBP2 in endometrial
      cancer cells. Mechanistically, the Sp1 site on the IGFBP2 promoter was required
      for RAD001- and M4N-induced downregulation. IGFBP2 protein expression was higher
      in endometrial cancer than in the normal endometrium (P < 0.001). Furthermore,
      elevated IGFBP2 histoscores were significantly associated with a lower overall
      survival (P = 0.021). In conclusion, our in vitro results demonstrate that RAD001
      and M4N exert synergistic antiproliferative effects against endometrial cancer
      cells, which appeared to be mediated by the inhibition of IGFBP2, a key anti
      apoptotic regulator. Further clinical studies of this drug combination in
      patients with endometrial cancer may be warranted, especially in the presence of
      PIK3CA and IGFBP2 aberrations. KEY MESSAGES: RAD001 and M4N synergistically
      suppress endometrial cancer growth. IGFBP2 is overexpressed in endometrial
      cancer. The combination of RAD001 and M4N significantly reduces IGFBP2
      overexpression. Sp1 binding site on the IGFBP2 promoter is required for RAD001-
      and M4N-induced downregulation. High IGFBP2 histoscore in endometrial cancer
      portends a poor prognosis.

PMID- 30298387
TI  - Darvadstrocel: A Review in Treatment-Refractory Complex Perianal Fistulas in
      Crohn's Disease.
AB  - Darvadstrocel (Alofisel(r)) consists of a suspension of expanded human allogeneic
      adipose-derived mesenchymal stem cells (eASCs). It is the first mesenchymal stem
      cell (MSC) advanced therapy approved in the EU for the treatment of complex
      perianal fistulas in adult patients with non-active/mildly active luminal Crohn's
      disease, when fistulas have shown an inadequate response to >= 1 conventional or
      biologic therapy. In the pivotal phase 3 ADMIRE-CD trial in this difficult-to
      treat patient population, after standard-of-care fistula conditioning, add-on
      therapy with a single dose of darvadstrocel (120 million eASC) administered into
      the tissue surrounding complex perianal fistulas was significantly more effective
      than placebo (saline), with the darvadstrocel group having a higher combined
      remission rate (i.e. clinically-assessed fistula closure plus MRI-assessed
      absence of abscesses) at 24 weeks in intent-to-treat (ITT primary analysis),
      modified ITT and per-protocol analyses. Clinical remission was maintained in >
      50% of patients at 52 weeks' follow-up. Given the very limited treatment options
      available for this difficult-to-treat rare condition, darvadstrocel is a
      promising, novel, minimally invasive therapy that represents an important advance
      in the therapeutic options for complex perianal fistulas in adult patients with
      non-active/mildly active luminal Crohn's disease when fistulas have shown an
      inadequate response to >= 1 conventional or biologic therapy.

PMID- 30298388
TI  - BABY BOOM (BBM): a candidate transcription factor gene in plant biotechnology.
AB  - Plants have evolved a number of transcription factors, many of which are
      implicated in signaling pathways as well as regulating diverse cellular
      functions. BABY BOOM (BBM), transcription factors of the AP2/ERF family are key
      regulators of plant cell totipotency. Ectopic expression of the BBM gene,
      originally identified in Brassica napus, has diverse functions in plant cell
      proliferation, growth and development without exogenous growth regulators. The
      BBM gene has been implicated to play an important role as a gene marker in
      multiple signaling developmental pathways in plant development. This review
      focuses on recent advances in our understanding of a member of the AP2 family of
      transcription factor BBM in plant biotechnology including plant embryogenesis,
      cell proliferation, regeneration, plant transformation and apogamy. Recent
      discoveries about the BBM gene will inevitably help to unlock the long-standing
      mysteries of different biological mechanisms of plant cells.

PMID- 30298386
TI  - Citations, non-citations and visibility of International Orthopaedics in 2017.

PMID- 30298389
TI  - Predicting the Effect of Mutations on Protein Folding and Protein-Protein
      Interactions.
AB  - The function of a protein is largely determined by its three-dimensional
      structure and its interactions with other proteins. Changes to a protein's amino
      acid sequence can alter its function by perturbing the energy landscapes of
      protein folding and binding. Many tools have been developed to predict the
      energetic effect of amino acid changes, utilizing features describing the
      sequence of a protein, the structure of a protein, or both. Those tools can have
      many applications, such as distinguishing between deleterious and benign
      mutations and designing proteins and peptides with attractive properties. In this
      chapter, we describe how to use one of such tools, ELASPIC, to predict the effect
      of mutations on the stability of proteins and the affinity between proteins, in
      the context of a human protein-protein interaction network. ELASPIC uses a wide
      range of sequential and structural features to predict the change in the Gibbs
      free energy for protein folding and protein-protein interactions. It can be used
      both through a web server and as a stand-alone application. Since ELASPIC was
      trained using homology models and not crystal structures, it can be applied to a
      much broader range of proteins than traditional methods. It can leverage
      precalculated sequence alignments, homology models, and other features, in order
      to drastically lower the amount of time required to evaluate individual mutations
      and make tractable the analysis of millions of mutations affecting the majority
      of proteins in a genome.

PMID- 30298390
TI  - Accurate Calculation of Free Energy Changes upon Amino Acid Mutation.
AB  - Molecular dynamics based free energy calculations allow for a robust and accurate
      evaluation of free energy changes upon amino acid mutation in proteins. In this
      chapter we cover the basic theoretical concepts important for the use of
      calculations utilizing the non-equilibrium alchemical switching methodology. We
      further provide a detailed step-by-step protocol for estimating the effect of a
      single amino acid mutation on protein thermostability. In addition, the potential
      caveats and solutions to some frequently encountered issues concerning the non
      equilibrium alchemical free energy calculations are discussed. The protocol
      comprises details for the hybrid structure/topology generation required for
      alchemical transitions, equilibrium simulation setup, and description of the fast
      non-equilibrium switching. Subsequently, the analysis of the obtained results is
      described. The steps in the protocol are complemented with an illustrative
      practical application: a destabilizing mutation in the Trp cage mini protein. The
      concepts that are described are generally applicable. The shown example makes use
      of the pmx software package for the free energy calculations using Gromacs as a
      molecular dynamics engine. Finally, we discuss how the current protocol can
      readily be adapted to carry out charge-changing or multiple mutations at once, as
      well as large-scale mutational scans.

PMID- 30298391
TI  - Protocols for the Molecular Evolutionary Analysis of Membrane Protein Gene
      Duplicates.
AB  - Gene duplication is an important process in the evolution of gene content in
      eukaryotic genomes. Understanding when gene duplicates contribute new molecular
      functions to genomes through molecular adaptation is one important goal in
      comparative genomics. In large gene families, however, characterizing adaptation
      and neofunctionalization across species is challenging, as models have
      traditionally quantified the timing of duplications without considering
      underlying gene trees. This protocol combines multiple approaches to detect
      adaptation in protein duplicates at a phylogenetic scale. We include a
      description of models for gene tree-species tree reconciliation that enable
      different types of inference, as well as a practical guide to their use. Although
      simulation-based approaches successfully detect shifts in the rate of
      duplication/retention, the conflation between the duplication and retention
      processes, the distinct trajectories of duplicates under non-, sub-, and
      neofunctionalization, as well as dosage effects offer hitherto unexplored
      analytical avenues. We introduce mathematical descriptions of these probabilities
      and offer a road map to computational implementation whose starting point is
      parsimony reconciliation. Sequence evolution information based on the ratio of
      nonsynonymous to synonymous nucleotide substitution rates (dN/dS) can be combined
      with duplicate survival probabilities to better predict the emergence of new
      molecular functions in retained duplicates. Together, these methods enable
      characterization of potentially adaptive candidate duplicates whose
      neofunctionalization may contribute to phenotypic divergence across species.

PMID- 30298392
TI  - Computational Prediction of De Novo Emerged Protein-Coding Genes.
AB  - De novo genes, that is, protein-coding genes originating from previously
      noncoding sequence, have gone from being considered impossibly unlikely to being
      recognized as an important source of genetic novelty in eukaryotic genomes. It is
      clear that de novo gene evolution is a rare but consistent feature of eukaryotic
      genomes, being detected in every genome studied. However, different studies often
      use different computational methods, and the numbers and identities of the
      detected genes vary greatly. Here we present a coherent protocol for the
      computational identification of de novo genes by comparative genomics. The method
      described uses homology searches, identification of syntenic regions, and
      ancestral sequence reconstruction to produce high-confidence candidates with
      robust evidence of de novo emergence. It is designed to be easily applicable
      given the basic knowledge of bioinformatic tools and scalable so that it can be
      applied on large and small datasets.

PMID- 30298393
TI  - Coevolutionary Signals and Structure-Based Models for the Prediction of Protein
      Native Conformations.
AB  - The analysis of coevolutionary signals from families of evolutionarily related
      sequences is a recent conceptual framework that provides valuable information
      about unique intramolecular interactions and, therefore, can assist in the
      elucidation of biomolecular conformations. It is based on the idea that
      compensatory mutations at specific residue positions in a sequence help preserve
      stability of protein architecture and function and leave a statistical signature
      related to residue-residue interactions in the 3D structure of the protein.
      Consequently, statistical analysis of these correlated mutations in subsets of
      protein sequence alignments can be used to predict which residue pairs should be
      in spatial proximity in the native functional protein fold. These predicted
      signals can be then used to guide molecular dynamics (MD) simulations to predict
      the three-dimensional coordinates of a functional amino acid chain. In this
      chapter, we introduce a general and efficient methodology to perform
      coevolutionary analysis on protein sequences and to use this information in
      combination with computational physical models to predict the native 3D
      conformation of functional polypeptides. We present a step-by-step methodology
      that includes the description and application of software tools and databases
      required to infer tertiary structures of a protein fold. The general pipeline
      includes instructions on (1) how to obtain direct amino acid couplings from
      protein sequences using direct coupling analysis (DCA), (2) how to incorporate
      such signals as interaction potentials in Calpha structure-based models (SBMs) to
      drive protein-folding MD simulations, (3) a procedure to estimate secondary
      structure and how to include such estimates in the topology files required in the
      MD simulations, and (4) how to build full atomic models based on the top Calpha
      candidates selected in the pipeline. The information presented in this chapter is
      self-contained and sufficient to allow a computational scientist to predict
      structures of proteins using publicly available algorithms and databases.

PMID- 30298394
TI  - Detecting Amino Acid Coevolution with Bayesian Graphical Models.
AB  - The comparative study of homologous proteins can provide abundant information
      about the functional and structural constraints on protein evolution. For
      example, an amino acid substitution that is deleterious may become permissive in
      the presence of another substitution at a second site of the protein. A popular
      approach for detecting coevolving residues is by looking for correlated
      substitution events on branches of the molecular phylogeny relating the protein
      coding sequences. Here we describe a machine learning method (Bayesian graphical
      models) implemented in the open-source phylogenetic software package HyPhy,
      http://hyphy.org , for extracting a network of coevolving residues from a
      sequence alignment.

PMID- 30298395
TI  - Context-Dependent Mutation Effects in Proteins.
AB  - Defining the extent of epistasis-the nonindependence of the effects of mutations
      is essential for understanding the relationship of genotype, phenotype, and
      fitness in biological systems. The applications cover many areas of biological
      research, including biochemistry, genomics, protein and systems engineering,
      medicine, and evolutionary biology. However, the quantitative definitions of
      epistasis vary among fields, and the analysis beyond just pairwise effects can be
      problematic. Here, we demonstrate the application of a particular mathematical
      formalism, the weighted Walsh-Hadamard transform, which unifies a number of
      different definitions of epistasis. We provide a computational implementation of
      such analysis using a computer-generated higher-order mutational dataset. We
      discuss general considerations regarding the null hypothesis for independent
      mutational effects, which then allows a quantitative identification of epistasis
      in an experimental dataset.

PMID- 30298396
TI  - High-Throughput Reconstruction of Ancestral Protein Sequence, Structure, and
      Molecular Function.
AB  - Ancestral protein sequence reconstruction is a powerful technique for explicitly
      testing hypotheses about the evolution of molecular function, allowing
      researchers to meticulously dissect how historical changes in protein sequence
      impacted functional repertoire by altering the protein's 3D structure. These
      techniques have provided concrete, experimentally validated insights into ancient
      evolutionary processes and help illuminate the complex relationship between
      protein sequence, structure, and function. Inferring the protein family
      phylogenies on which ancestral sequence reconstruction depends and reconstructing
      the sequences, themselves, are amenable to high-throughput computational
      analysis. However, determining the structures of ancestral-reconstructed proteins
      and characterizing their functions typically rely on time-consuming and expensive
      laboratory analyses, limiting most current studies to examining a relatively
      small number of specific hypotheses. For this reason, we have little detailed,
      unbiased information about how molecular function evolves across large protein
      family phylogenies. Here we describe a generalized protocol that integrates
      ancestral sequence reconstruction with structural homology modeling and structure
      based molecular affinity prediction to characterize historical changes in protein
      function across families with thousands of individual sequences. We highlight key
      steps in the analysis protocol requiring particularly careful attention to avoid
      introducing potential errors as well as steps for which computationally efficient
      subroutines can be substituted for more intensive approaches, allowing
      researchers to scale the analysis up or down, depending on available resources
      and requirements for reproducibility and scientific rigor. In our view, this
      approach provides a compelling compliment to more laboratory-intensive
      procedures, generating important contextual information that can help guide
      detailed experiments.

PMID- 30298397
TI  - Ancestral Sequence Reconstruction as a Tool for the Elucidation of a Stepwise
      Evolutionary Adaptation.
AB  - Ancestral sequence reconstruction (ASR) is a powerful tool to infer primordial
      sequences from contemporary, i.e., extant ones. An essential element of ASR is
      the computation of a phylogenetic tree whose leaves are the chosen extant
      sequences. Most often, the reconstructed sequence related to the root of this
      tree is of greatest interest: It represents the common ancestor (CA) of the
      sequences under study. If this sequence encodes a protein, one can "resurrect"
      the CA by means of gene synthesis technology and study biochemical properties of
      this extinct predecessor with the help of wet-lab experiments.However, ASR
      deduces also sequences for all internal nodes of the tree, and the well
      considered analysis of these "intermediates" can help to elucidate evolutionary
      processes. Moreover, one can identify key mutations that alter proteins or
      protein complexes and are responsible for the differing properties of extant
      proteins. As an illustrative example, we describe the protocol for the rapid
      identification of hotspots determining the binding of the two subunits within the
      heteromeric complex imidazole glycerol phosphate synthase.

PMID- 30298398
TI  - Enhancing Statistical Multiple Sequence Alignment and Tree Inference Using
      Structural Information.
AB  - For highly divergent sequences, there is often insufficient information to
      reliably construct alignments and phylogenetic trees. Since protein structure may
      be strongly conserved despite large divergences in sequence, structural
      information can be used to help identify homology in such cases.While there exist
      well-studied models of sequence evolution, structurally informed alignment
      methods have typically made use of geometric measures of deviation that do not
      take into account the underlying mutational processes. In order to integrate
      structural information into sequence-based evolutionary models, we recently
      developed a stochastic model of structural evolution on a phylogenetic tree and
      implemented this as the StructAlign plugin for the StatAlign statistical
      alignment package.In this chapter, we will outline the types of analyses that can
      be carried out using StructAlign, illustrating how the inclusion of structural
      information can be used to inform joint estimation of alignments and trees.
      StructAlign can also be used to infer branch-specific rates of structural
      evolution, and analysis of an example globin dataset highlights strong variation
      in the inferred rate across the tree. While structure is more highly conserved
      within clades, the rate of structural divergence as a function of sequence
      variation is larger between functionally divergent proteins. Allowing for the
      rate of structural divergence to vary over the tree results in an improved fit to
      the empirically observed pairwise RMSD values.

PMID- 30298399
TI  - The Influence of Protein Stability on Sequence Evolution: Applications to
      Phylogenetic Inference.
AB  - Phylogenetic inference from protein data is traditionally based on empirical
      substitution models of evolution that assume that protein sites evolve
      independently of each other and under the same substitution process. However, it
      is well known that the structural properties of a protein site in the native
      state affect its evolution, in particular the sequence entropy and the
      substitution rate. Starting from the seminal proposal by Halpern and Bruno, where
      structural properties are incorporated in the evolutionary model through site
      specific amino acid frequencies, several models have been developed to tackle the
      influence of protein structure on sequence evolution. Here we describe stability
      constrained substitution (SCS) models that explicitly consider the stability of
      the native state against both unfolded and misfolded states. One of them, the
      mean-field model, provides an independent sites approximation that can be readily
      incorporated in maximum likelihood methods of phylogenetic inference, including
      ancestral sequence reconstruction. Next, we describe its validation with
      simulated and real proteins and its limitations and advantages with respect to
      empirical models that lack site specificity. We finally provide guidelines and
      recommendations to analyze protein data accounting for stability constraints,
      including computer simulations and inferences of protein evolution based on
      maximum likelihood. Some practical examples are included to illustrate these
      procedures.

PMID- 30298400
TI  - Navigating Among Known Structures in Protein Space.
AB  - Present-day protein space is the result of 3.7 billion years of evolution,
      constrained by the underlying physicochemical qualities of the proteins. It is
      difficult to differentiate between evolutionary traces and effects of
      physicochemical constraints. Nonetheless, as a rule of thumb, instances of
      structural reuse, or focusing on structural similarity, are likely attributable
      to physicochemical constraints, whereas sequence reuse, or focusing on sequence
      similarity, may be more indicative of evolutionary relationships. Both types of
      relationships have been studied and can provide meaningful insights to protein
      biophysics and evolution, which in turn can lead to better algorithms for protein
      search, annotation, and maybe even design.In broad strokes, studies of protein
      space vary in the entities they represent, the similarity measure comparing these
      entities, and the representation used. The entities can be, for example, protein
      chains, domains, supra-domains, or smaller protein sub-parts denoted themes. The
      measures of similarity between the entities can be based on sequence, structure,
      function, or any combination of these. The representation can be global,
      encompassing the whole space, or local, focusing on a particular region
      surrounding protein(s) of interest. Global representations include lists of
      grouped proteins, protein networks, and maps. Networks are the abstraction that
      is derived most directly from the similarity data: each node is the protein
      entity (e.g., a domain), and edges connect similar domains. Selecting the
      entities, the similarity measure, and the abstraction are three intertwined
      decisions: the similarity measures allow us to identify the entities, and the
      selection of entities influences what is a meaningful similarity measure.
      Similarly, we seek entities that are related to each other in a way, for which a
      simple representation describes their relationships succinctly and accurately.
      This chapter will cover studies that rely on different entities, similarity
      measures, and a range of representations to better understand protein structure
      space. Scholars may use publicly available navigators offering a global
      representation, and in particular the hierarchical classifications SCOP, CATH,
      and ECOD, or a local representation, which encompass structural alignment
      algorithms. Alternatively, scholars can configure their own navigator using
      existing tools. To demonstrate this DIY (do it yourself) approach for navigating
      in protein space, we investigate substrate-binding proteins. By presenting
      sequence similarities among this large and diverse protein family as a network,
      we can infer that one member (pdb ID 4ntl; of yet unknown function) may bind
      methionine and suggest a putative binding mechanism.

PMID- 30298401
TI  - A Graph-Based Approach for Detecting Sequence Homology in Highly Diverged Repeat
      Protein Families.
AB  - Reconstructing evolutionary relationships in repeat proteins is notoriously
      difficult due to the high degree of sequence divergence that typically occurs
      between duplicated repeats. This is complicated further by the fact that proteins
      with a large number of similar repeats are more likely to produce significant
      local sequence alignments than proteins with fewer copies of the repeat motif.
      Furthermore, biologically correct sequence alignments are sometimes impossible to
      achieve in cases where insertion or translocation events disrupt the order of
      repeats in one of the sequences being aligned. Combined, these attributes make
      traditional phylogenetic methods for studying protein families unreliable for
      repeat proteins, due to the dependence of such methods on accurate sequence
      alignment.We present here a practical solution to this problem, making use of
      graph clustering combined with the open-source software package HH-suite, which
      enables highly sensitive detection of sequence relationships. Carrying out
      multiple rounds of homology searches via alignment of profile hidden Markov
      models, large sets of related proteins are generated. By representing the
      relationships between proteins in these sets as graphs, subsequent clustering
      with the Markov cluster algorithm enables robust detection of repeat protein
      subfamilies.

PMID- 30298402
TI  - Exploring Enzyme Evolution from Changes in Sequence, Structure, and Function.
AB  - The goal of our research is to increase our understanding of how biology works at
      the molecular level, with a particular focus on how enzymes evolve their
      functions through adaptations to generate new specificities and mechanisms.
      FunTree (Sillitoe and Furnham, Nucleic Acids Res 44:D317-D323, 2016) is a
      resource that brings together sequence, structure, phylogenetic, and chemical and
      mechanistic information for 2340 CATH superfamilies (Sillitoe et al., Nucleic
      Acids Res 43:D376-D381, 2015) (which all contain at least one enzyme) to allow
      evolution to be investigated within a structurally defined superfamily.We will
      give an overview of FunTree's use of sequence and structural alignments to
      cluster proteins within a superfamily into structurally similar groups (SSGs) and
      generate phylogenetic trees augmented by ancestral character estimations (ACE).
      This core information is supplemented with new measures of functional similarity
      (Rahman et al., Nat Methods 11:171-174, 2014) to compare enzyme reactions based
      on overall bond changes, reaction centers (the local environment atoms involved
      in the reaction), and the structural similarities of the metabolites involved in
      the reaction. These trees are also decorated with taxonomic and Enzyme Commission
      (EC) code and GO annotations, forming the basis of a comprehensive web interface
      that can be found at http://www.funtree.info . In this chapter, we will discuss
      the various analyses and supporting computational tools in more detail,
      describing the steps required to extract information.

PMID- 30298403
TI  - Identification of Protein Homologs and Domain Boundaries by Iterative Sequence
      Alignment.
AB  - Evolutionary domains are protein regions with observable sequence similarity to
      other known domains. Here we describe how to use common sequence and profile
      alignment algorithms (i.e., BLAST, HHsearch) to delineate putative domains in
      novel protein sequences, given a reference library of protein domains. In this
      case, we use our database of evolutionary domains (ECOD) as a reference, but
      other domain sequence libraries could be used (e.g., SCOP, CATH). We describe our
      domain partition algorithm along with specific notes on how to avoid domain
      indexing errors when working with multiple data sources and software algorithms
      with differing outputs.

PMID- 30298404
TI  - A Roadmap to Domain Based Proteomics.
AB  - Protein domains are reusable segments of proteins and play an important role in
      protein evolution. By combining the elements from a relatively small set of
      domains into unique arrangements, a large number of distinct proteins can be
      generated. Since domains often have specific functions, changes in their
      arrangement usually affect the overall protein function. Furthermore, domains are
      well amenable to computational representations, e.g., by Hidden Markov Models
      (HMMs), and these HMMs are widely represented in various databases. Therefore,
      domains can be efficiently used for proteomic analyses. Here, we describe how
      domains are annotated using different domain databases and then how to assess the
      annotation quality of proteomes. We next show how functional annotations of
      domains in large-scale data such as whole genomes or transcriptomes can be used
      to analyze molecular differences between species. Furthermore, we describe
      methods to analyze the changes in domain content of proteins which significantly
      helps to characterize and reconstruct the modular evolution of proteins.
      Altogether, domain-based methods offer a computationally highly effective
      approach to analyze large amounts of proteomic data in an evolutionary setting.

PMID- 30298405
TI  - Modeling of Protein Tertiary and Quaternary Structures Based on Evolutionary
      Information.
AB  - Proteins are subject to evolutionary forces that shape their three-dimensional
      structure to meet specific functional demands. The knowledge of the structure of
      a protein is therefore instrumental to gain information about the molecular basis
      of its function. However, experimental structure determination is inherently time
      consuming and expensive, making it impossible to follow the explosion of sequence
      data deriving from genome-scale projects. As a consequence, computational
      structural modeling techniques have received much attention and established
      themselves as a valuable complement to experimental structural biology efforts.
      Among these, comparative modeling remains the method of choice to model the three
      dimensional structure of a protein when homology to a protein of known structure
      can be detected.The general strategy consists of using experimentally determined
      structures of proteins as templates for the generation of three-dimensional
      models of related family members (targets) of which the structure is unknown.
      This chapter provides a description of the individual steps needed to obtain a
      comparative model using SWISS-MODEL, one of the most widely used automated
      servers for protein structure homology modeling.

PMID- 30298407
TI  - Predicting Functions of Disordered Proteins with MoRFpred.
AB  - Intrinsically disordered proteins and regions are involved in a wide range of
      cellular functions, and they often facilitate protein-protein interactions.
      Molecular recognition features (MoRFs) are segments of intrinsically disordered
      regions that bind to partner proteins, where binding is concomitant with a
      transition to a structured conformation. MoRFs facilitate translation, transport,
      signaling, and regulatory processes and are found across all domains of life. A
      popular computational tool, MoRFpred, accurately predicts MoRFs in protein
      sequences. MoRFpred is implemented as a user-friendly web server that is freely
      available at http://biomine.cs.vcu.edu/servers/MoRFpred/ . We describe this
      predictor, explain how to run the web server, and show how to interpret the
      results it generates. We also demonstrate the utility of this web server based on
      two case studies, focusing on the relevance of evolutionary conservation of MoRF
      regions.

PMID- 30298406
TI  - Interface-Based Structural Prediction of Novel Host-Pathogen Interactions.
AB  - About 20% of the cancer incidences worldwide have been estimated to be associated
      with infections. However, the molecular mechanisms of exactly how they contribute
      to host tumorigenesis are still unknown. To evade host defense, pathogens hijack
      host proteins at different levels: sequence, structure, motif, and binding
      surface, i.e., interface. Interface similarity allows pathogen proteins to
      compete with host counterparts to bind to a target protein, rewire physiological
      signaling, and result in persistent infections, as well as cancer. Identification
      of host-pathogen interactions (HPIs)-along with their structural details at
      atomic resolution-may provide mechanistic insight into pathogen-driven cancers
      and innovate therapeutic intervention. HPI data including structural details is
      scarce and large-scale experimental detection is challenging. Therefore, there is
      an urgent and mounting need for efficient and robust computational approaches to
      predict HPIs and their complex (bound) structures. In this chapter, we review the
      first and currently only interface-based computational approach to identify novel
      HPIs. The concept of interface mimicry promises to identify more HPIs than
      complete sequence or structural similarity. We illustrate this concept with a
      case study on Kaposi's sarcoma herpesvirus (KSHV) to elucidate how it subverts
      host immunity and helps contribute to malignant transformation of the host cells.

PMID- 30298408
TI  - Exploring Protein Conformational Diversity.
AB  - The native state of proteins is composed of conformers in dynamical equilibrium.
      In this chapter, different issues related to conformational diversity are
      explored using a curated and experimentally based database called CoDNaS
      (Conformational Diversity in the Native State). This database is a collection of
      redundant structures for the same sequence. CoDNaS estimates the degree of
      conformational diversity using different global and local structural similarity
      measures. It allows the user to explore how structural differences among
      conformers change as a function of several structural features providing further
      biological information. This chapter explores the measurement of conformational
      diversity and its relationship with sequence divergence. Also, it discusses how
      proteins with high conformational diversity could affect homology modeling
      techniques.

PMID- 30298409
TI  - High-Throughput Antibody Structure Modeling and Design Using ABodyBuilder.
AB  - Antibodies are proteins of the adaptive immune system; they can be designed to
      bind almost any molecule, and are increasingly being used as biotherapeutics.
      Experimental antibody design is an expensive and time-consuming process, and
      computational antibody design methods can now be used to help develop new
      therapeutics and diagnostics. Within the design pipeline, accurate antibody
      structure modeling is essential, as it provides the basis for antibody-antigen
      docking, binding affinity prediction, and estimating thermal stability. Ideally,
      models should be rapidly generated, allowing the exploration of the breadth of
      antibody space. This allows methods to replicate the natural processes of
      antibody diversification (e.g., V(D)J recombination and somatic hypermutation),
      and cope with large volumes of data that are typical of next-generation
      sequencing datasets. Here we describe ABodyBuilder and PEARS, algorithms that
      build and mutate antibody model structures. These methods take ~30 s to generate
      a model antibody structure.

PMID- 30298410
TI  - In Silico-Directed Evolution Using CADEE.
AB  - Recent years have seen an explosion of interest in both sequence- and structure
      based approaches toward in silico-directed evolution. We recently developed a
      novel computational toolkit, CADEE, which facilitates the computer-aided directed
      evolution of enzymes. Our initial work (Amrein et al., IUCrJ 4:50-64, 2017)
      presented a pedagogical example of the application of CADEE to triosephosphate
      isomerase, to illustrate the CADEE workflow. In this contribution, we describe
      this workflow in detail, including code input/output snippets, in order to allow
      users to set up and execute CADEE simulations on any system of interest.

PMID- 30298411
TI  - Open-label placebo reduces fatigue in cancer survivors: a randomized trial.
AB  - PURPOSE: Cancer-related fatigue (CRF) is a common and challenging late effect for
      many cancer survivors. Clinical trials demonstrate robust placebo effects on CRF
      in blinded trials. Recently, open-label placebo (OLP) has been shown to improve a
      variety of symptoms in other populations. We conducted a randomized controlled
      trial to investigate the effect of OLP on CRF in cancer survivors, and to explore
      biologic and psychological correlates of placebo efficacy. METHODS: Forty cancer
      survivors (92.5% female; mean age 47.3 years) were randomized to OLP or no
      treatment control. OLP participants were prescribed two placebo tablets twice
      daily, for 3 weeks. All participants completed assessments at Baseline, Day 8,
      and Day 22. The primary endpoint was change in CRF (FACIT-F), and secondary
      outcomes included exercise frequency, mood, and quality of life. We examined
      whether personality characteristics or a genetic variation important in dopamine
      catabolism (catechol-O-methyltransferase; COMT) affected the placebo response.
      RESULTS: The OLP group reported significantly improved CRF at both Day 8 (p =
      0.005) and Day 22 (p = .02), while the control group did not (ps > .05). CRF
      improvement differed by COMT genotype, but was not associated with personality
      characteristics. Marginal improvements were noted in the placebo group for some
      secondary outcomes (exercise frequency and quality of life), but not in the
      control group. CONCLUSIONS: Results demonstrate that even when administered
      openly, placebos improve CRF in cancer survivors and dopaminergic systems may be
      associated with this response. This novel research has meaningful implications
      for the use of OLP in symptom management for cancer survivors.

PMID- 30298412
TI  - Short- vs long-course antibiotic therapy for pneumonia: a comparison of
      systematic reviews and guidelines for the SIMI Choosing Wisely Campaign.
AB  - Reduction of the inappropriate use of antibiotics in clinical practice is one of
      the main goals of the Societa Italiana di Medicina Interna (SIMI) choosing wisely
      campaign. We conducted a systematic review of secondary studies (systematic
      reviews and guidelines) to verify what evidence is available on the duration of
      antibiotic treatment in Pneumonia. A literature systematic search was performed
      to identify all systematic reviews and the three most cited and recent guidelines
      that address the duration of antibiotic therapy in pneumonia. Moreover, a meta
      analysis of non-duplicate data from randomized controlled trials (RCTs)
      considered in the enrolled systematic reviews was performed together with a trial
      sequential analysis to identify the need for further studies. Two systematic
      reviews on antibiotic duration in community-acquired pneumonia (CAP) for a total
      of 17 RCTs (2764 patients) were enrolled in our study. Meta-analysis of non
      duplicate RCTs show a non-significant difference in rate of treatment failure
      between short (<= 7 days) and long (> 7 days) antibiotic treatment course: RR
      1.05 (95% CI, 0.82-1.36). The trial sequential analysis suggests that further
      data would not affect current evidence or become clinically relevant. Selected
      guidelines suggest consideration of a short course, with a low grade of evidence
      and without citing the already published systematic reviews. Antibiotic treatment
      of CAP for <= 7 days is not associated with a higher rate of treatment failure
      than longer courses and should thus be taken in consideration. Guidelines should
      upgrade the evidence on this topic.

PMID- 30298413
TI  - The discrepancy between patient expectations and actual outcome reduces at the
      first 6 months following total knee replacement surgery.
AB  - PURPOSE: Patients undergoing total knee arthroplasty often have unfulfilled
      expectations from the surgery that can lead to dissatisfaction. This study aimed
      to examine the discrepancy between patients' expectations and actual functional
      abilities prior to undergoing knee replacement surgery, and at 6 and 12 months
      following the surgery. METHODS: A survey was undertaken of patients before, and 6
      and 12 months post-surgery. The survey included the Knee Surgery Perception
      Questionnaire (KSPQ) to assess patients' current perception of their level of
      function and pain, their desired outcomes, and the discrepancy between the two.
      Pain, function and quality of life were also assessed. Repeated measure ANOVAs
      were used to assess differences between pre- and post-surgery. RESULTS: A total
      of 176 patients were surveyed. Significant differences in the KSPQ discrepancy
      scores (subscale and total scores) were demonstrated between the three assessment
      point times (p < 0.01). Paired t tests identified significant differences between
      the pre-surgery and 6-month KSPQ discrepancy scores, (p < 0.01) indicative of
      substantial improvement in physical function and slight reduction in
      expectations. Overall significant improvement (p < 0.01) was reported over time
      across all measures: physical function, pain and stiffness and quality of life.
      CONCLUSION: The discrepancy between patients' current abilities and their
      expectation changes following surgery, especially in the first 6 months post
      surgery. Patients' goals might change as their function and pain improve post
      surgery. Combining education programmes and discussion with the treating
      orthopaedic surgeons pre-operatively is important for the development of
      realistic, achievable expectations. LEVEL OF EVIDENCE: III.

PMID- 30298414
TI  - Improved results of ACL primary repair in one-part tears with intact synovial
      coverage.
AB  - PURPOSE: It was the aim to assess the influence of synovial sheath disruption on
      early failure of primary anterior cruciate ligament (ACL) repair. It was
      hypothesized that more-part ACL tears with disruption of the synovial sheath are
      associated with a higher risk of failure after primary ACL repair. METHODS: A
      cohort study was conducted comprising patients with primal ACL tears undergoing
      primary ACL repair and dynamic intraligamentary stabilization (DIS). The patients
      were stratified into three groups: A-one-part rupture with intact synovial
      membrane (n = 50), B-two-part ruptures resultant to separation of the ACL into
      two main bundles with synovial membrane tearing (n = 52) and C-more parts
      involving multilacerated ruptures with membrane disruption (n = 22). Failure was
      defined as a retear or residual laxity (anterior posterior translation > 5 mm
      compared to healthy knee). Adjustment for potential risk factors was performed
      using a multivariate logistic-regression model. RESULTS: The overall failure rate
      was 17.7% throughout the mean follow-up period of 2.3 +/- 0.8 years. The failure
      rate in patients with one-part ACL tears with an intact synovial membrane was 4%
      (n = 2) (Group A), which was significantly lower than the failure rates in groups
      B and C, 26.9% (n = 14) (p = 0.001) and 27.3% (n = 6) (p = 0.003), respectively.
      Disruption of the synovial sheath in two- or more-part tears was identified as an
      independent factor influencing treatment failure in primary ACL repair (OR 8.9;
      95% CI 2.0-40.0). CONCLUSION: The integrity of the ACL bundles and synovial
      sheath is a factor that influences the success of ACL repair. This needs to be
      considered intra-operatively when deciding about repair. LEVEL OF EVIDENCE: IV.

PMID- 30298415
TI  - High risk of tunnel convergence during combined anterior cruciate ligament and
      anterolateral ligament reconstruction.
AB  - PURPOSE: To assess the risk of femoral tunnel convergence in combined anterior
      cruciate ligament (ACL) and anterolateral ligament (ALL) reconstructions. The
      hypothesis was that a more proximal and anterior orientation of the ALL femoral
      tunnel should reduce the risk of convergence with the ACL femoral tunnel.
      METHODS: 15 fresh-frozen cadaver knees were examined. An anatomic ACL femoral
      tunnel was drilled arthroscopically in each specimen and ALL tunnels were made in
      two directions: (1) 0 degrees  coronal angulation and 20 degrees  axial
      angulation, (2) 30 degrees  coronal angulation and 30 degrees  axial angulation.
      Computed tomography scans were performed to investigate tunnel convergence and to
      measure the minimal distance between tunnels, tunnel length and the LFC width.
      RESULTS: Tunnel convergence occurred in 20 of 30 cases (67%). Convergence was
      significantly reduced when tunnels were drilled at 30 degrees  coronal and 30
      degrees  axial angulation (p < 0.05). The mean length of the ALL tunnel was 15.9
      mm [95% CI (13.6; 18.1)] and was independent of ALL tunnel angulation. The mean
      minimal distance between the ALL and ACL tunnel was 3.1 mm [95% CI (2.1; 4.1)].
      The odds ratio for tunnel convergence was 3.5 for small LFC, relative to large
      LFC (n.s.) CONCLUSION: A high risk of tunnel convergence was observed when
      performing combined ACL and ALL reconstructions. The clinical relevance of this
      work is that the occurrence of tunnel conflicts can be reduced by aiming the ALL
      tunnel in a more proximal and anterior direction. Surgeons should be aware of
      this, since tunnel convergence could jeopardize the ACL reconstruction and
      fixation.

PMID- 30298417
TI  - Effect of Perioperative High Oxygen Concentration on Postoperative SSI in
      Elective Colorectal Surgery-A Randomized Controlled Trial.
AB  - BACKGROUND: This study was carried out to investigate the effect of perioperative
      high oxygen concentration on surgical site infection (SSI) in patients undergoing
      elective colorectal surgery. METHODS: This was a single-center, prospective,
      parallel arm, double-blind, superiority randomized controlled trial. All patients
      more than 18 years of age undergoing elective colorectal surgery were included as
      per the inclusion criteria. Patients were randomized at the time of induction of
      anesthesia into high concentration and standard concentration oxygen group based
      on the concentration of oxygen. Incidence of SSI, day of the detection of SSI,
      grade of SSI, incidence of anastomotic leak, postoperative day of return of bowel
      functions, day of starting oral feeds, day of ambulation, and length of
      hospitalization were studied in both the groups. RESULTS: A total of 94 patients
      were included in the study, 47 patients each in high concentration oxygen group
      and standard concentration oxygen group respectively. The SSI rates were
      comparable between the two groups [55.3% (95% CI-4.012-69.83) vs. 40.4% (95% CI
      26.37-55.73); p = 0.215]. There was no significant difference found with respect
      to mean day of detection of SSI [4.5(IQR-3.0-7.5) vs. 6.0 (IQR-3.0-9.0; p =
      0.602], postoperative day of return of bowel functions (2.20 +/- 0.542 vs. 2.13
      +/- 0.582; p = 0.540), oral feeds (3.62 +/- 0.945 vs. 3.46 +/- 1.048; p = 0.544),
      ambulation (4.17 +/- 0.868 vs. 4.17 +/- 1.270; p = 0.987), and the length of
      hospitalization [15(IQR-10-19) vs. 15(IQR-10.75-18.25); p = 0.862] between the
      two groups. CONCLUSION: There was no significant difference in the rate of SSI
      with the use of perioperative high oxygen concentration in patients undergoing
      elective colorectal surgery.

PMID- 30298416
TI  - A Novel Strategy of Laparoscopic Insufflation Rate Improving Shoulder Pain:
      Prospective Randomized Study.
AB  - BACKGROUND: Laparoscopic surgery is the main trend method in a variety of
      surgical fields. Post-operative shoulder pain remains a bothersome issue although
      many surgical techniques have been applied to minimize it. A simple novel
      approach to reduce shoulder pain without adverse effects during and after
      laparoscopic surgery is desired. METHODS: This prospective randomized controlled
      study was conducted to enroll a total of 140 patients to evaluate the efficacy of
      low flow rate (1 L/min) for induction followed by high flow rate (10 L/min) for
      maintaining 12 mmHg pneumoperitoneum (group A, n = 70) during laparoscopic
      cholecystectomy (LC), compared to the continuous high flow rate group (group B, n
      = 70) in postoperative shoulder pain and other clinical features. The 10-visual
      analog scale (VAS) was applied for the severity of shoulder pain and scores were
      obtained at 1, 6, 12, 24, and 48 h after LC. RESULTS: There was no obvious
      difference in baseline characteristics as well as operative time, occurrence of
      bradycardia, or hospital stay between groups. The incidence of shoulder pain was
      not significantly different (group A 45.7% vs group B 48.6%, p = 0.866). However,
      the patients in group A with shoulder pain reported significantly less pain
      scores (p < 0.001) at 12 and 24 h after surgery, compared with those in group B.
      CONCLUSIONS: Applying the strategy of low flow rate to induce pneumoperitoneum
      followed by high flow rate to maintain the pressure provides advantages to reduce
      the severity of shoulder pain for patients who underwent LC and then experienced
      shoulder pain.

PMID- 30298418
TI  - Comparison of Long-term Quality of Life in Patients with Esophageal Cancer after
      Ivor-Lewis, Mckeown, or Sweet Esophagectomy.
AB  - BACKGROUND: The aim of this study was to compare the long-term quality of life
      (QoL) in patients after Sweet, Ivor-Lewis, or Mckeown esophagectomy. METHODS:
      Esophageal cancer patients after Sweet, Ivor-Lewis, or Mckeown esophagectomy from
      2010 to 2012 were included. QoL was assessed according to the European
      Organization for Research and Treatment of Cancer general questionnaire: QLQ-C30
      and esophagus-specific questionnaire: QLQ-OES18. RESULTS: A total of 126
      qualified patients who have been alive for more than 3 years without tumor
      recurrence were divided into three groups: the Sweet group (n = 40), Ivor-Lewis
      group (n = 38), and Mckeown group (n = 48). Among these three groups, the QLQ-C30
      mean scores of global health status, functional and symptom scales, and general
      QoL were similar. The symptom scales of QLQ-OSE18 showed that patients who had a
      Mckeown operation experienced more problem of eating (P = 0.029), choking when
      swallowing (P = 0.010) and coughing (P = 0.016), while patients undergoing Sweet
      operation complained more symptom of reflux (P = 0.003) and pain (P = 0.000).
      CONCLUSIONS: All three types of esophagectomy provided a generally good long-term
      QoL. However, patients in Sweet and Mckeown group tend to suffer from a higher
      symptomatic burden as compared to Ivor-Lewis approach.

PMID- 30298419
TI  - Post-Discharge Opioid Prescribing Patterns and Risk Factors in Patients
      Undergoing Elective Colon and Rectal Surgery Without Complications.
AB  - BACKGROUND: Few studies have examined opioid usage in the post-discharge period.
      The primary aim of this study was to evaluate the need for post-discharge opioids
      in a unique set of patients: those undergoing colorectal operations and
      experiencing no surgical complications. The secondary aim was to examine the
      accuracy of the Opioid Risk Tool (ORT) to predict the need for additional opioid
      prescriptions. Our hypotheses were that few patients would require post-discharge
      opioids and that the ORT would predict patients requiring post-discharge opioids.
      METHODS: All patients undergoing elective colorectal surgery between January 2012
      and December 2014 that did not experience NSQIP complications within 30 days or
      receive an opioid prescription in the 2 weeks prior to operation were reviewed.
      ORT score was calculated for all patients. Patients requiring post-discharge
      opioids within 1 year were compared to those not receiving additional opioids
      after discharge. RESULTS: There were 367 patients that met inclusion criteria and
      56 (15%) received post-discharge opioids. Opioid use in the year prior to surgery
      was the only significant risk factor to receive post-discharge opioids. Opioids
      were prescribed for three distinct reasons by three groups of prescribers. The
      ORT did not accurately predict need for post-discharge opioids. CONCLUSIONS: Even
      among patients without complications, 15% received post-discharge opioid
      prescriptions. Previous opioid use within the year prior to surgery was a major
      risk factor for additional prescriptions. The timing and prescriber's specialty
      are impacted by the indication for post-discharge opioids. The ORT did not
      predict which patients would receive post-discharge opioids.

PMID- 30298421
TI  - Primary Sarcomatoid Malignant Mesothelioma of the Pancreas.

PMID- 30298420
TI  - Slow Gait Speed Is a Risk Factor for Complications After Hepatic Resection.
AB  - PURPOSE: The aims of this study were to clarify the relationship of gait speed,
      hand grip strength, and skeletal muscle mass with complications after hepatic
      resection and to identify risk factors for complications in patients who
      underwent hepatic resection. METHODS: We evaluated the risk factors for
      complications after hepatic resection in 154 consecutive patients. Preoperative
      factors included gait speed, hand grip strength, and skeletal muscle mass. The
      gait speed and hand grip strength of patients were measured by physical
      therapists, and skeletal muscle mass was measured by computed tomography.
      Multivariate logistic regression analyses using preoperative factors were
      performed to assess predictors of the development of complications after hepatic
      resection. RESULTS: Thirty-three patients (21.4%) developed complications after
      hepatic resection. These patients had a significantly lower serum albumin level
      (p = 0.015), slower gait speed (p = 0.007), higher rate of hepatic resection >= 2
      Couinaud segments (p = 0.014), and lower rate of laparoscopic hepatic resection
      (p = 0.017) than patients without complications. Multivariate analysis revealed
      that a gait speed <= 1.10 m/s and a serum albumin level of <= 4.0 g/dl were
      independent risk factors for complications after hepatic resection. CONCLUSIONS:
      Slow gait speed and low serum albumin level are significant risk factors for
      complications after hepatic resection. These data will be helpful for
      perioperative patient management.

PMID- 30298422
TI  - Use of Activity Tracking in Major Visceral Surgery-the Enhanced Perioperative
      Mobilization Trial: a Randomized Controlled Trial.
AB  - BACKGROUND: Early mobilization is one essential item within the enhanced recovery
      after surgery (ERAS) concept, but lacks solid evidence and a standardized
      assessment. The aim was to monitor and increase the postoperative mobilization of
      patients after major visceral surgery by providing a continuous step count
      feedback using activity tracking wristbands. METHODS: The study was designed as a
      randomized controlled single-center trial (NCT02834338) with two arms (open and
      laparoscopic surgery). Participants were randomized to either receive feedback of
      their step counts using an activity tracker wristband or not. The primary study
      endpoint was the mean step count during the first 5 postoperative days (PODs).
      RESULTS: A total of 132 patients were randomized. After laparoscopic operations,
      the average step count during PODs 1-5 was significantly increased by the
      feedback compared with the control group (P < 0.001); the cumulative step count
      (9867 versus 6103, P = 0.037) and activity time were also significantly
      increased. These results could not be confirmed in the open surgery arm. Possible
      reasons were a higher age and significantly more comorbidities in the open
      intervention group. Patients who achieved more than the median cumulative step
      count had a significantly shorter hospital stay and lower morbidity in both arms.
      The average step count also correlated with the length of hospital stay (R = -
      0.341, P < 0.001). CONCLUSION: This study is the first randomized controlled
      trial investigating the use and feasibility of activity tracking to monitor and
      enhance postoperative mobilization in abdominal surgery. Our results demonstrate
      that activity tracking can enhance perioperative mobilization after laparoscopic
      surgery. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02834338.

PMID- 30298423
TI  - A new NBIA patient from Turkey with homozygous C19ORF12 mutation.

PMID- 30298424
TI  - Apolipoproteins A1, B, and apoB/apoA1 ratio are associated with first ST-segment
      elevation myocardial infarction but not with recurrent events during long-term
      follow-up.
AB  - INTRODUCTION: The current way to assess the risk of cardiovascular disease (CVD)
      is to measure conventional lipid and lipoprotein cholesterol fractions. Despite
      the success of statin treatment, residual cardiovascular risk remains high.
      Therefore, the value of extensive serum apolipoprotein (apo) profiling to assess
      the risk of ST-segment elevation myocardial infarction (STEMI) and of major
      adverse cardiac events (MACE) in patients with STEMI was investigated in a case
      control design. METHODS AND RESULTS: Serum apo levels were measured using liquid
      chromatography and mass spectrometry in 299 healthy individuals and 220 patients
      with STEMI. First, the association of apo profiles in baseline samples with risk
      of STEMI was examined, and second, the association of apo profiles at baseline
      with risk of recurrent MACE in patients with STEMI in a longitudinal study design
      was studied. High baseline (> 1.25 g/L) apoA1 levels were associated with a
      decreased risk of STEMI [odds ratio (OR) 0.17; 95% CI 0.11-0.26], whereas high
      apoB (> 1.00 g/L) levels (OR 2.17; 95% CI 1.40-3.36) and apoB/apoA1 ratio (OR per
      1 SD (OR/SD): 2.16; 95% CI 1.76-2.65) were associated with an increased risk.
      Very-low-density-lipoprotein (VLDL)-associated apos gave conflicting results.
      Neither conventional lipid levels nor apo levels were associated with MACE in the
      STEMI group. CONCLUSION: In conclusion, apoA1, apoB, and apoB/apoA1 were strongly
      associated with risk of STEMI. No clear relation between VLDL-associated apos and
      the risk of STEMI was found. Neither baseline serum apos nor lipids predicted
      MACE in statin-treated patients during long-term follow-up after a first STEMI.

PMID- 30298425
TI  - Alterations in structural rich-club connectivity of the precuneus are associated
      with depressive symptoms among individuals with subjective memory complaints.
AB  - The association between subjective memory complaints (SMCs) and depressive
      symptoms has been widely reported and both have been regarded as risk factors for
      dementia, such as Alzheimer's disease (AD). Although SMCs arise as early as in
      middle age, the exact neural correlates of comorbid depressive symptoms among
      individuals who are middle-aged and with SMCs have not yet been well
      investigated. Because rich-club organization of the brain plays a key role in the
      pathophysiology of various neuropsychiatric disorders, the investigation of rich
      club organization may provide insight regarding the neurobiological mechanisms of
      depressive symptoms in SMCs. In the current study, we compared the rich-club
      organization in the structural brain connectivity between individuals who have
      SMCs along with depressive symptoms (SMCD) and individuals with SMCs but without
      depressive symptoms (SMCO). A total of 53 individuals with SMCD and 91
      individuals with SMCO participated in the study. For all participants, high
      resolution, T1-weighted images and diffusion tensor images were obtained, and the
      network analysis was performed. Individuals with SMCD had lower connectivity
      strength between the precuneus and other rich-club nodes than those with SMCO,
      which was significant after adjusting for potential confounders. Our findings
      suggest that disruptions of rich-club connectivity strength of the precuenus are
      associated with depressive symptoms in middle-aged individuals with SMCs. Given
      that the precuneus is one of the commonly affected regions in the early stages of
      AD, our findings may imply that the concomitant depressive symptoms in middle
      aged individuals with SMCs could reflect structural alterations related to AD.

PMID- 30298426
TI  - Congenital pseudoaneurysm of the mitral-aortic intervalvular fibrosa with a 5
      years' follow up.

PMID- 30298427
TI  - Frond transformation system mediated by Agrobacterium tumefaciens for Lemna
      minor.
AB  - The Lemnaceae, known as duckweed, the smallest flowering aquatic plant, shows
      promise as a plant bioreactor. For applying this potential plant bioreactor,
      establishing a stable and efficient genetic transformation system is necessary.
      The currently favored callus-based method for duckweed transformation is time
      consuming and genotype limited, as it requires callus culture and regeneration,
      which is inapplicable to many elite duckweed strains suitable for bioreactor
      exploitation. In this study, we attempted to establish a simple frond
      transformation system mediated by Agrobacterium tumefaciens for Lemna minor, one
      of the most widespread duckweed species in the world. To evaluate the feasibility
      of the new transformation system, the gene CYP710A11 was overexpressed to improve
      the yield of stigmasterol, which has multiple medicinal purposes. Three L. minor
      strains, ZH0055, D0158 and M0165, were transformed by both a conventional callus
      transformation system (CTS) and the simple frond transformation system (FTS). GUS
      staining, PCR, quantitative PCR and stigmasterol content detection showed that
      FTS can produce stable transgenic lines as well as CTS. Moreover, compared to
      CTS, FTS can avoid the genotype constraints of callus induction, thus saving at
      least half of the required processing time (CTS took 8-9 months while FTS took
      approximately 3 months in this study). Therefore, this transformation system is
      feasible in producing stable transgenic lines for a wide range of L. minor
      genotypes.

PMID- 30298428
TI  - Comparative analysis of selection mode reveals different evolutionary rate and
      expression pattern in Arachis duranensis and Arachis ipaensis duplicated genes.
AB  - KEY MESSAGE: Our results reveal that Ks is a determining factor affecting
      selective pressure and different evolution and expression patterns are detected
      between PSGs and NSGs in wild Arachis duplicates. Selective pressure, including
      purifying (negative) and positive selection, can be detected in organisms.
      However, studies on comparative evolutionary rates, gene expression patterns and
      gene features between negatively selected genes (NSGs) and positively selected
      genes (PSGs) are lagging in paralogs of plants. Arachis duranensis and Arachis
      ipaensis are ancestors of the cultivated peanut, an important oil and protein
      crop. Here, we carried out a series of systematic analyses, comparing NSG and PSG
      in paralogs, using genome sequences and transcriptome datasets in A. duranensis
      and A. ipaensis. We found that synonymous substitution rate (Ks) is a determining
      factor affecting selective pressure in A. duranensis and A. ipaensis duplicated
      genes. Lower expression level, lower gene expression breadth, higher codon bias
      and shorter polypeptide length were found in PSGs and not in NSGs. The
      correlation analyses showed that gene expression breadth was positively
      correlated with polypeptide length and GC content at the first codon site (GC1)
      in PSGs and NSGs, respectively. There was a negative correlation between
      expression level and polypeptide length in PSGs. In NSGs, the Ks was positively
      correlated with expression level, gene expression breadth, GC1, and GC content at
      the third codon site (GC3), but selective pressure was negatively correlated with
      expression level, gene expression breadth, polypeptide length, GC1, and GC3
      content. The function of most duplicated gene pairs was divergent under drought
      and nematode stress. Taken together, our results show that different evolution
      and expression patterns occur between PSGs and NSGs in paralogs of two wild
      Arachis species.

PMID- 30298430
TI  - Normal pancreatic volume in adults is influenced by visceral fat, vertebral body
      width and age.
AB  - OBJECTIVES: The aim was to describe the pancreatic volume (PV) in a cohort of
      subjects with no prior history of pancreatic disease, and to explore the
      relationship between PV and conventional two-point measurements of the pancreas.
      Associations between PV, gender, age, abdominal body composition, and human
      height were explored as well. METHODS: CT scans from 204 trauma patients (20-80
      years, 100 males) were evaluated. PV was measured with semi-automatic
      segmentation. Standardized two-point measurements of the pancreas were obtained
      together with L1 vertebral body size (a proxy for human height) and abdominal
      body composition. Associations between PV and the other parameters were explored
      using uni- and multivariate linear regression. RESULTS: The mean PV was 77.9 +/-
      21.7(SD) cm3 with an interindividual variability from 18.8 to 139.8 cm3. The
      transversal diameter of the pancreatic head showed the strongest correlation to
      PV (r = 0.500, p < 0.001). Age, width of the L1 vertebral body, and visceral fat
      cross-sectional area were all independently associated with PV (all p < 0.001),
      while no independent association was seen for gender (p = 0.441). CONCLUSIONS:
      The pancreatic volume is subject to a large interindividual variability and is
      associated with age, human height and body composition, while gender had no
      independent influence on the pancreatic volume. Thus, future studies using PV as
      an outcome parameter should be evaluated in the context of anthropometric
      profiles.

PMID- 30298429
TI  - Novel osteoconductive beta-tricalcium phosphate/poly(L-lactide-co-e-caprolactone)
      scaffold for bone regeneration: a study in a rabbit calvarial defect.
AB  - The advantages of synthetic bone graft substitutes over autogenous bone grafts
      include abundant graft volume, lack of complications related to the graft
      harvesting, and shorter operation and recovery times for the patient. We studied
      a new synthetic supercritical CO2 -processed porous composite scaffold of beta
      tricalcium phosphate and poly(L-lactide-co-caprolactone) copolymer as a bone
      graft substitute in a rabbit calvarial defect. Bilateral 12 mm diameter critical
      size calvarial defects were successfully created in 18 rabbits. The right defect
      was filled with a scaffold moistened with bone marrow aspirate, and the other was
      an empty control. The material was assessed for applicability during surgery. The
      follow-up times were 4, 12, and 24 weeks. Radiographic and micro-CT studies and
      histopathological analysis were used to evaluate new bone formation, tissue
      ingrowth, and biocompatibility. The scaffold was easy to shape and handle during
      the surgery, and the bone-scaffold contact was tight when visually evaluated
      after the implantation. The material showed good biocompatibility and its
      porosity enabled rapid invasion of vasculature and full thickness mesenchymal
      tissue ingrowth already at four weeks. By 24 weeks, full thickness bone ingrowth
      within the scaffold and along the dura was generally seen. In contrast, the empty
      defect had only a thin layer of new bone at 24 weeks. The radiodensity of the
      material was similar to the density of the intact bone. In conclusion, the new
      porous scaffold material, composed of microgranular beta-TCP bound into the
      polymer matrix, proved to be a promising osteoconductive bone graft substitute
      with excellent handling properties.

PMID- 30298431
TI  - Sex and sex steroids impact influenza pathogenesis across the life course.
AB  - Males and females differ in the outcome of influenza A virus (IAV) infections,
      which depends significantly on age. During a typical seasonal influenza epidemic,
      young children (< 10 years of age) and aged adults (65+ years of age) are at
      greatest risk for severe disease, and among these age groups, males tend to
      suffer a worse outcome from IAV infection than females. Following infection with
      either pandemic or outbreak strains of IAVs, females of reproductive ages (i.e.,
      15-49 years of age) experience a worse outcome than their male counterparts.
      Among females of reproductive ages, pregnancy is one factor linked to an
      increased risk of severe outcome of influenza, although it is not the sole factor
      explaining the female-preponderance of severe disease. Small animal models of
      influenza virus infection illustrate that inflammatory immune responses and
      repair of damaged tissue following IAV infection also differ between the sexes
      and impact the outcome of infection. There also is growing evidence that sex
      steroid hormones, including estrogens, progesterone, and testosterone, directly
      impact immune responses during IAV infection to alter outcomes. Greater
      consideration of the combined effects of sex and age as biological variables in
      epidemiological, clinical, and animal studies of influenza pathogenesis is
      needed.

PMID- 30298432
TI  - Developmental origin and sex-specific risk for infections and immune diseases
      later in life.
AB  - The intrauterine environment is an important determinant of immunity later in
      life of the offspring. An altered prenatal immune development can result in a
      high postnatal risk for infections, chronic immune diseases, and autoimmunity.
      Many of these immune diseases show a strong sex bias, such as a high incidence of
      autoimmune diseases and allergies in adult females or a high risk for infections
      in males. Here, we comprehensively review established pathways and propose novel
      concepts modulating the risk for such poor immunity during childhood and
      throughout life. Moreover, we highlight how an adverse fetal environment may
      affect or aggravate the risk for poor immunity in a sex-specific manner. An
      improved understanding of a sex-specific susceptibility to poor immunity along
      with insights on how such risk can be modulated before or around birth will allow
      the development of tailored prevention strategies.

PMID- 30298433
TI  - The microgenderome revealed: sex differences in bidirectional interactions
      between the microbiota, hormones, immunity and disease susceptibility.
AB  - Sex differences in immunity are well described in the literature and thought to
      be mainly driven by sex hormones and sex-linked immune response genes. The
      gastrointestinal tract (GIT) is one of the largest immune organs in the body and
      contains multiple immune cells in the GIT-associated lymphoid tissue, Peyer's
      patches and elsewhere, which together have profound effects on local and systemic
      inflammation. The GIT is colonised with microbial communities composed of
      bacteria, fungi and viruses, collectively known as the GIT microbiota. The GIT
      microbiota drives multiple interactions locally with immune cells that regulate
      the homeostatic environment and systemically in diverse tissues. It is becoming
      evident that the microbiota differs between the sexes, both in animal models and
      in humans, and these sex differences often lead to sex-dependent changes in local
      GIT inflammation, systemic immunity and susceptibility to a range of inflammatory
      diseases. The sexually dimorphic microbiome has been termed the 'microgenderome'.
      Herein, we review the evidence for the microgenderome and contemplate the role it
      plays in driving sex differences in immunity and disease susceptibility. We
      further consider the impact that biological sex might play in the response to
      treatments aimed at manipulating the GIT microbiota, such as prebiotics, live
      biotherapeutics, (probiotics, synbiotics and bacteriotherapies) and faecal
      microbial transplant. These alternative therapies hold potential in the treatment
      of both psychological (e.g., anxiety, depression) and physiological (e.g.,
      irritable bowel disease) disorders differentially affecting males and females.

PMID- 30298435
TI  - Evaluating Completeness of a Radiology Glossary Using Iterative Refinement.
AB  - A lay-language glossary of radiology, built to help patients better understand
      the content of their radiology reports, has been analyzed for its coverage and
      readability, but not for its completeness. We present an iterative method to
      sample radiology reports, identify "missing" terms, and measure the glossary's
      completeness. We hypothesized that the refinement process would reduce the number
      of missing terms to fewer than 1 per report. A random sample of 1000 radiology
      reports from a large US academic health system was divided into 10 cohorts of 100
      reports each. Each cohort was reviewed in sequence by two investigators to
      identify terms (single words and multi-word phrases) absent from the glossary.
      Terms marked as new were added to the glossary and hence was shown as matched in
      subsequent cohorts. This HIPAA-compliant study was IRB-approved; informed consent
      was waived. The refinement process added a mean of 288.0 new terms per 100
      reports in the first 5 cohorts vs. a mean of 66.0 new terms per 100 reports in
      the last 5 cohorts; the difference was statistically significant (p < .01). After
      reviewing 500 reports, the review process found fewer than 1 new term per report
      in each of 500 subsequent reports. The findings suggest that 500 to 1000 reports
      is adequate to test the completeness of a glossary, and that the glossary after
      iterative refinement achieved a high level of completeness to cover the
      vocabulary of radiology reports.

PMID- 30298436
TI  - Utilization of Structured Reporting to Monitor Outcomes of Doppler Ultrasound
      Performed for Deep Vein Thrombosis.
AB  - Determining the clinical impact of imaging exams at the enterprise level is
      problematic, as radiology reports historically have been created with the content
      meant primarily for the referring provider. Structured reporting can establish
      the foundation for enterprise monitoring of imaging outcomes without manual
      review providing the framework for assessment of utilization and quality.
      Ultrasound (US) for deep vein thrombosis evaluation (DVT) is an ideal testbed for
      assessing this functionality. The system standard template for Doppler US for
      extremity venous evaluation for DVT was updated with a discrete fixed picklist of
      impression options and implemented system wide. Template utilization and
      interpretive outcomes were actively monitored and use reinforced as part of
      standard clinical practice. From January 1, 2017 to December 31, 2017, 9111 US
      exams for DVT were performed with 8997 utilizing structured reporting (98.75%).
      Of those in the structured reporting group, 1074 (11.79%) were positive for any
      type of DVT with 732 (8.03%) reported as Acute/New above the knee. Positive rates
      for any type of DVT were 10.29% emergency department, 14.17% inpatient, and
      13.20% outpatient. While being the lowest positive rate, the emergency department
      had the highest overall volume of exams. Structured reporting for DVT US
      assessment outcomes can be implemented with a very high rate of radiologist
      adoption and adherence providing accurate determination of positive rates, month
      by month, in differing patient locations. Structured elements can be used to
      automatically trigger downstream processes; in our institution, this will alert
      providers in the EHR if the patient does not receive anticoagulation within 2 h
      of a positive test. This lays the foundation for effective enterprise assessment
      of imaging outcomes forming the basis of future quality and safety initiatives on
      optimizing health system resource utilization.

PMID- 30298434
TI  - Tissue Physiology of Cynomolgus Monkeys: Cross-Species Comparison and
      Implications for Translational Pharmacology.
AB  - We previously performed a comparative assessment of tissue-level vascular
      physiological parameters in mice and rats, two of the most commonly utilized
      species in translational drug development. The present work extends this effort
      to non-human primates by measuring tissue- and organ-level vascular volumes (Vv),
      interstitial volumes (Vi), and blood flow rates (Q) in cynomolgus monkeys. These
      measurements were accomplished by red blood cell labeling, extracellular marker
      infusion, and rubidium chloride bolus distribution, respectively, the same
      methods used in previous rodent measurements. In addition, whole-body blood
      volumes (BV) were determined across species. The results demonstrate that Vv, Vi,
      and Q, measured using our methods scale approximately by body weight across
      mouse, rat, and monkey in the tissues considered here, where allometric analysis
      allowed extrapolation to human parameters. Significant differences were observed
      between the values determined in this study and those reported in the literature,
      including Vv in muscle, brain, and skin and Q in muscle, adipose, heart, thymus,
      and spleen. The impact of these differences for selected tissues was evaluated
      via sensitivity analysis using a physiologically based pharmacokinetic model. The
      blood-brain barrier in monkeys was shown to be more impervious to an infused
      radioactive tracer, indium-111-pentetate, than in mice or rats. The body weight
      normalized total BV measured in monkey agreed well with previously measured value
      in rats but was lower than that in mice. These findings have important
      implications for the common practice of scaling physiological parameters from
      rodents to primates in translational pharmacology.

PMID- 30298437
TI  - The Role of the Integrated Digital Radiology System in Assessing the Impact of
      Patient Load on Emergency Computed Tomography (CT) Efficiency.
AB  - Time-critical management is of particular significance in the trauma and
      emergency setting, where intervals from patient arrival to diagnostic imaging and
      from imaging to radiology report are key determinants of outcome. This study,
      based in the Trauma and Emergency Unit of a large, tertiary-level African
      hospital with a fully digital radiology department, assessed the impact of
      increased workload on computerised tomography (CT) efficiency. Sequential,
      customised searches of the institutional radiology information system (RIS) were
      conducted to define two weekends in 2016 with the lowest and highest emergency CT
      workloads, respectively. The electronic RIS timestamps defining the intervals
      between key steps in the CT workflow were extracted and analysed for each
      weekend. With the exception of radiologist reporting time, workflow steps were
      significantly prolonged by increased workload. This study highlights the
      potential role of the integrated digital radiology system in enabling a detailed
      analysis of imaging workflow, thereby facilitating the identification and
      appropriate management of bottlenecks.

PMID- 30298438
TI  - How clinicians integrate humanism in their clinical workplace-'Just trying to put
      myself in their human being shoes'.
AB  - INTRODUCTION: Humanism has been identified as an important contributor to patient
      care and physician wellness; however, what humanism means in the context of
      medicine has been limited by opinion and a focus on personal characteristics. Our
      aim was to describe attitudes and behaviours that enable clinicians to integrate
      humanism within the clinical setting. METHODS: We conducted semi-structured
      individual interviews with ten clinical faculty to explore how they enact and
      experience humanism in patient care and clinical teaching. Interpretive
      description was used to analyze the data qualitatively. RESULTS: Humanism in
      medicine was described through five themes representing core attitudes and
      behaviours: whole person care, valuing, perspective-taking, recognizing
      universality, and relational focus. Whole person care involved recognizing the
      multiple dimensions of personhood and sensitivity to others' needs; valuing
      involved respecting and appreciating others; perspective-taking consisted of
      considering others' perspectives, suspending judgment, and listening; recognizing
      universality involved acknowledging the shared human condition, finding common
      ground, transcending roles, and humility; and relational focus was described
      through multiple relationships between patients, families, clinicians and
      learners, becoming part of another's story, reciprocal influence, and
      accompaniment. CONCLUSIONS: Whereas previous descriptions of humanism have
      focused on clinicians' personal qualities, our research describes a number of
      attitudinal and behavioural foundations of humanistic care and teaching, grounded
      in the experiences of clinical faculty. In drawing attention to the holistic and
      relational elements of humanism, our work highlights how these foundational
      elements can be more explicitly integrated into patient care, workplace culture,
      and clinical education.

PMID- 30298440
TI  - Correction to: Disparities in the Treatment of Substance Use Disorders: Does
      Where You Live Matter?
AB  - The professional degree of co-author Kevin Campbell is incorrect. It should be
      "DrPH" and not "PhD".

PMID- 30298439
TI  - The use of PBPK modeling across the pediatric age range using propofol as a case.
AB  - The project SAFEPEDRUG aims to provide guidelines for drug research in children,
      based on bottom-up and top-down approaches. Propofol, one of the studied model
      compounds, was selected because it is extensively metabolized in liver and
      kidney, with an important role for the glucuronidation pathway. Besides, being a
      lipophilic molecule, it is distributed into fat tissues, from where it
      redistributes into the systemic circulation. In the past, both bottom-up
      (Physiologically based pharmacokinetic, PBPK) and top-down approaches (population
      pharmacokinetic, popPK) were applied to describe its pharmacokinetics (PK). In
      this work, a combination of the two was used to check their performance to
      describe PK in children and neonates (both term and preterm) using propofol as a
      case compound. First, in vitro data was generated in human liver microsomes and
      recombinant enzymes and used to develop an adult PBPK model in Simcyp(r).
      Activity adjustment factors (AAFs) were calculated to account for differences
      between in vitro and in vivo enzyme activity. Clinical data were analyzed using a
      3-compartment model in NONMEM. These data were used to construct a retrograde
      PBPK model and for qualification of the PBPK models. Once an accurate in vivo
      clearance was obtained accounting for the contribution of the different metabolic
      pathways, the resulting PBPK models were challenged with new data for
      qualification. After that, the constructed adult PPBK model for propofol was
      extrapolated to the pediatric population. Both the default built-in and in vivo
      derived ontogeny functions were used to do so. The models were qualified by
      comparing their predicted PK parameters to published values, and by comparison of
      predicted concentration-time profiles to available clinical data. Clearance
      values were predicted well, especially when compared with values obtained from
      trials where long-term sampling was applied, whereas volume of distribution was
      lower compared to the most common popPK model predictions. Concentration-time
      profiles were predicted well up until and including the preterm neonatal
      population. In this work, it was thus shown that PBPK can be used to predict the
      PK up to and including the preterm neonatal population without the use of
      pediatric in vivo data. This work adds weight to the need for further development
      of PBPK models, especially regarding distribution modeling and the use of in vivo
      derived ontogeny functions.

PMID- 30298441
TI  - How Do Early Psychosis Services Define and Operationalize the Duration of
      Untreated Psychosis?
AB  - Reducing the duration of untreated psychosis (DUP) is a key aim of early
      psychosis (EP) care. However, substantial variability in how the start and end
      points of DUP are defined impact its utility in clinical decision-making, and as
      an outcome measure. In this study, qualitative interviews were conducted with
      providers to assess how EP services and providers define, operationalize, and
      measure DUP. Twenty-five providers across 14 clinics were interviewed.
      Participants emphasized symptom frequency, conviction, distress caused, and
      impact when determining psychosis onset. DUP endpoint was typically identified as
      the first assessment in an episode of care that included an accurate diagnosis,
      leading to specialty EP treatment. Participants proposed a more structured
      operationalization of DUP, relative to those historically adopted in the
      literature. Integrating front-line provider perspectives could improve the
      accuracy of DUP measurement and address the heterogeneity in how the construct is
      operationalized across research and practice.

PMID- 30298442
TI  - Mental Health Service Preferences and Utilization Among Women Veterans in Crisis:
      Perspectives of Veterans Crisis Line Responders.
AB  - Women military veterans are at increased risk of suicide compared to non
      veterans, but little is known about the mental health service preferences and
      needs of women veterans in crisis. This study used qualitative, secondary source
      key informant interviews to ascertain the experiences of women veterans in crisis
      from 54 responders working at the Veterans Crisis Line. Responders indicated that
      women veterans reported different experiences with Veterans Administration (VA)
      and non-VA care, though drivers of satisfaction or dissatisfaction were similar.
      Availability of specialty care, sensitivity to veterans' issues or Military
      Sexual Trauma, strong provider relationships, and continuity of care contributed
      to satisfaction; lengthy appointment wait times, limited service options, and
      insensitivity to veterans' issues contributed to dissatisfaction. Responders
      suggested that barriers limiting VA access for women veterans are perceived as
      similar to non-VA care. Findings suggest that caller experiences with providers
      drive satisfaction with VA and non-VA mental health services.

PMID- 30298444
TI  - Glucagon-Like Peptide-1 Infusion Suppresses Aldosterone Levels in Healthy Normal
      Weight Individuals: Double-Blind, Placebo-Controlled Crossover Study.
AB  - INTRODUCTION: Glucagon-like peptide-1 (GLP-1) has many effects on the human body,
      but its glucose-lowering effect through its stimulation of insulin secretion is
      the most significant. GLP-1 also acts on renal function and hemodynamics. The
      antihypertensive and renoprotective effects of GLP-1 receptor agonists are partly
      explained by their vasoactive effect and increased natriuresis, but their
      positive influences on blood pressure and the development and progression of
      kidney disease are attributed to many effects beyond glycemic control. The aim of
      this study was to determine how the native gut hormone GLP-1 influences the renin
      angiotensin-aldosterone system (RAAS). METHODS: Fourteen healthy participants (6
      males and 8 females) were included in a double-blind, placebo-controlled
      crossover study. After overnight fasting and oral sodium loading, participants
      were randomly assigned to receive either placebo (500 ml of 0.9% saline) or GLP-1
      infusion (1.5 pmol/kg/min dissolved in 500 ml of 0.9% saline) over a 3-h period.
      After 3 and 6 h, the following parameters were measured: glucose, insulin, plasma
      renin activity, aldosterone, GLP-1, and antidiuretic hormone. After 7 days, the
      protocol was repeated, except that those who had previously received placebo now
      received GLP-1 infusion, and those who had previously received GLP-1 now received
      placebo. RESULTS: Three hours after GLP-1 infusion, aldosterone had decreased by
      a statistically significant amount (p < 0.008) compared to the baseline level.
      CONCLUSION: The present study showed that native GLP-1 can decrease aldosterone
      secretion in a group of healthy individuals, supporting the idea of beneficial
      outcomes of GLP-1-activating agents on blood pressure and the RAAS. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT02130778.

PMID- 30298443
TI  - Modulatory Effects of Levodopa on Cerebellar Connectivity in Parkinson's Disease.
AB  - Levodopa has been the mainstay of symptomatic therapy for Parkinson's disease
      (PD) for the last five decades. However, it is associated with the development of
      motor fluctuations and dyskinesia, in particular after several years of
      treatment. The aim of this study was to shed light on the acute brain functional
      reorganization in response to a single levodopa dose. Functional magnetic
      resonance imaging (fMRI) was performed after an overnight withdrawal of
      dopaminergic treatment and 1 h after a single dose of 250 mg levodopa in a group
      of 24 PD patients. Eigenvector centrality was calculated in both treatment states
      using resting-state fMRI. This offers a new data-driven and parameter-free
      approach, similar to Google's PageRank algorithm, revealing brain connectivity
      alterations due to the effect of levodopa treatment. In all PD patients, levodopa
      treatment led to an improvement of clinical symptoms as measured with the Unified
      Parkinson's Disease Rating Scale motor score (UPDRS-III). This therapeutic effect
      was accompanied with a major connectivity increase between cerebellar brain
      regions and subcortical areas of the motor system such as the thalamus, putamen,
      globus pallidus, and brainstem. The degree of interconnectedness of cerebellar
      regions correlated with the improvement of clinical symptoms due to the
      administration of levodopa. We observed significant functional cerebellar
      connectivity reorganization immediately after a single levodopa dose in PD
      patients. Enhanced general connectivity (eigenvector centrality) was associated
      with better motor performance as assessed by UPDRS-III score. This underlines the
      importance of considering cerebellar networks as therapeutic targets in PD.

PMID- 30298445
TI  - Impact of Definitive Drug-Drug Interaction Testing on Medication Management and
      Patient Care.
AB  - BACKGROUND AND OBJECTIVE: Aegis Sciences Corporation developed a test (InterACT
      RxTM) that objectively and definitively identifies substances known to interact
      with drug-drug interaction-prone medications commonly prescribed in the treatment
      of chronic pain and behavioral health disorders. The objective of this study was
      to assess the severity of identified drug-drug interactions, the reduction in the
      frequency and severity of identified drug-drug interactions, and the impact of
      the test on healthcare utilization. METHODS: Patients with chronic pain,
      behavioral health disorders, or both who had one or more drug-drug interaction
      tests and one or more drug-drug interactions identified in the study period were
      included. Drug-drug interaction test results described the number and severity of
      interactions and detected substances involved in drug-drug interactions.
      Patients' electronic medical records were obtained to analyze outpatient visits
      and prescription medications. The cost of outpatient visits was based on the
      Medicare Physician Fee Schedule. Outcomes were compared between the pre- and post
      study index periods to determine the impact of the drug-drug interaction test on
      patient care. RESULTS: A total of 262 patients were included. The majority of
      drug-drug interactions detected (77.9%) at index were of moderate severity. The
      number of monthly all-cause and pain-related outpatient visits was reduced in the
      post-index period compared with the pre-index period (0.74-0.54 and 0.69-0.49,
      respectively). Associated costs were reduced from US$64.92 to US$51.20, and from
      US$62.42 to US$47.62, (p < 0.0001 for both) for all-cause and pain-related
      outpatient visits, respectively. Follow-up drug-drug interaction testing for 43
      patients revealed that previously reported drug-drug interactions at the index
      test were no longer identified in the subsequent test for 39.5% of patients.
      CONCLUSIONS: Employing a definitive test to detect substances whose interactions
      may cause adverse drug events can enhance a provider's insights, drive clinical
      decision making, and improve patient outcomes.

PMID- 30298446
TI  - Laparoscopic transcystic common bile duct exploration: surgical indications and
      procedure strategies.
AB  - BACKGROUND: LTCBDE combined with or without modified techniques is safe and
      efficacious for the management of gallstones and concomitant, even large, common
      bile duct (CBD) stones. METHODS: To describe the surgical indications and
      procedure strategies of laparoscopic transcystic common bile duct exploration
      (LTCBDE), a retrospective analysis of 205 patients with concomitant gallstones
      and CBD stones treated using LTCBDE between June 2008 and June 2015 was
      performed. Clinical data on disease characteristics, methods for cystic duct
      incision and CBD stone extraction (with or without laser lithotripsy), and
      surgical outcomes were collected and reviewed. RESULTS: CBD stones were
      successfully cleared in all patients. No patient was converted to choledochotomy
      or laparotomy. The cystic duct diameter ranged 3-8 mm, and 85 patients with
      cystic duct diameter >= 5 mm. The mean time for CBD stone extraction was 25.3
      min, with the operative time ranged from 63 to 170 min. Lithotripsy was used in
      74 (36.1%) patients among which 26 patients with cystic duct diameter >= 5 mm.
      Estimated blood loss during surgery was 10-120 ml per patient, and no intra
      operative blood transfusions were needed. The mean postoperative hospital stay
      was 5.1 (range 3-7) days, and postoperative complications developed in seven
      patients. No bile duct injury, stricture, remnant, recurrent stones, or other
      adverse events were observed during the mean follow-up of 8 months. CONCLUSIONS:
      Based on preoperative MRCP and intra-operative IOC findings about cystic duct
      diameter, the diameter of CBD, CBD stone size, we summarized and proposed the
      surgical indications and suitable techniques and strategies during LTCBDE.

PMID- 30298447
TI  - The incidence of lymph node metastasis in submucosal early gastric cancer
      according to the expanded criteria: a systematic review.
AB  - BACKGROUND: For successful endoscopic treatment of early gastric cancer (EGC),
      absolute criteria for a curative en bloc resection were initially established to
      include predominantly differentiated mucosal lesions <= 2 cm in diameter without
      ulceration. These indications were subsequently expanded to include larger,
      ulcerated, and predominantly undifferentiated mucosal lesions. In addition,
      differentiated type adenocarcinomas <= 3 cm with slight submucosal invasion of <
      500 um (pT1b1) are regarded as "curative" under the expanded criteria. However,
      data derived from studies of surgical specimens in patients with pT1b1 EGC have
      yielded varying rates of lymph node metastasis (LNM). METHOD: A systemic review
      was conducted using the pooled analysis to calculate the incidence of LNM in
      pT1b1 EGC, and to investigate whether using a cut-off value of < 300 um would
      decrease the risk of LNM in patients with submucosal EGC. RESULTS: Nineteen
      articles were included. 1507 patients with pT1b1 EGC met the expanded
      indications. The incidence of LNM was 3% (45 out of 1507 patients). In a subgroup
      analysis of three studies, there was no significant difference in the LNM between
      pT1b EGC < 300 um and < 500 um [3/121(2.5%) vs. 5/180 (2.8%)] (OR 0.89, 95% CI
      0.22-3.54). CONCLUSION: Overall, expanding the indications for endoscopic
      resection of EGC to include lesions <= 3 cm T1b1 is associated with a potential
      risk of LNM of 3%. In countries outside of Japan, we found a slightly higher risk
      of LNM (4.0%). These estimates of LNM should be incorporated into decisions
      regarding further management of patients with EGC <= 3 cm who are found to have
      slight submucosal invasion (< 500 um) in an ESD specimen. Standardization of
      specimen handling and histological evaluation is essential if the Japanese
      results of endoscopic treatment for EGC are to be successfully applied in other
      parts of the world.

PMID- 30298448
TI  - Decreased autophagy was implicated in the decreased apoptosis during
      decidualization in early pregnant mice.
AB  - Folate deficiency is a major risk factor of birth defects. Mechanistic studies on
      folate deficiency resulting in birth defects have mainly focused on fetal
      development. There have been few studies on folate deficiency from the point of
      view of the mother's uterus. In our previous study, we demonstrated that folate
      deficiency inhibits apoptosis of decidual cells, thereby restraining
      decidualization of the endometrium and impairing pregnancy. In this study, we
      further investigated the potential mechanism by which folate deficiency decreases
      endometrial apoptosis during decidualization. To investigate whether endometrium
      autophagy was inhibited under folate deficiency during decidualization, we
      performed real-time PCR for endometrial LC3 and P62 on day 6 (D6) to D8 of
      pregnancy in mice, and both were significantly changed compared to non-folate
      deficient mice. Western blots showed that LC3-II and P62 were also changed in
      folate-deficient mice. Compared with control mice, a few punctuate LC3-II
      structures were detected in the folate deficiency group by immunofluorescence.
      Transmission electron micrographs of decidual cells on D8 showed that there were
      no evident autophagosomes in the folate deficiency group. In addition, apoptosis
      related protein analysis by western blotting, TUNEL staining and flow cytometry
      showed that decreased endometrial apoptosis on D8 of pregnancy under folate
      deficiency was reversed after treatment with rapamycin, an autophagy inducer. ROS
      measurement showed that the endometrium ROS level was reduced by folate
      deficiency and that rapamycin reversed this effect on day 8 of pregnancy. All the
      results suggest that inhibiting endometrial autophagy may be implicated in the
      decreased endometrial apoptosis under folate deficiency during decidualization.

PMID- 30298450
TI  - Engineering of deglycosylated and plasmin resistant variants of recombinant
      streptokinase in Pichia pastoris.
AB  - Streptokinase, a therapeutically important thrombolytic agent, is prone to C
      terminal degradation and plasmin-mediated proteolytic processing. Since the
      protein was glycosylated during secretion from Pichia pastoris, therefore, the
      role of carbohydrate moieties on its stability was analyzed via in vivo blocking
      of N-glycosylation using tunicamycin where an increased degradation of
      streptokinase was observed. Further, the in vitro site-directed mutagenesis of
      the three putative N-glycosylation sites at asparagine residues 14, 265, and 377
      to alanine revealed the essentiality of glycosylation of the 14th amino acid
      residue in its post-translational proteolytic stability without significantly
      affecting its biological activity. However, the mutation of both Asn265 and
      Asn377 did not seem to contribute toward its glycosylation but resulted in a 39%
      lower specific activity in case of the rSK-N265,377A. Moreover, the mutation of
      all three glycosylation positions drastically reduced the secretory expression of
      native streptokinase from 347 to 186.6 mg/L for the triple mutant with a 14%
      lower specific activity of 56,738 IU/mg from 65,808 IU/mg. The secondary
      structure, tertiary structure, and thermal transition point (45-55  degrees C) of
      all the deglycosylated variants did not show any significant differences when
      compared with fully glycosylated native streptokinase using CD and fluorescence
      spectroscopy. Furthermore, the longer acting plasmin-resistant variants were also
      developed via the mutation of lysine residues 59 and 386 to glutamine which
      enhanced its biological stability as a ~ 1.5-fold increase in the caseinolytic
      zone size was observed in case of rSK-K59Q and also in rSK-K59,386Q mutant
      without affecting the structural properties.

PMID- 30298449
TI  - Nur77 promotes cerebral ischemia-reperfusion injury via activating INF2-mediated
      mitochondrial fragmentation.
AB  - Mitochondrial fragmentation drastically regulates mitochondrial homeostasis in
      brain illness. However, the role of mitochondrial fragmentation in cerebral
      ischemia-reperfusion (IR) injury remains unclear. Nur77, a regulator of
      mitochondrial homeostasis, is associated with heart and liver IR injury, but its
      effects on mitochondrial function in cerebral IR injury has not been studied
      intensively. The aim of our study is to explore whether cerebral IR injury is
      modulated by Nur77 via modification of mitochondrial homeostasis. Our results
      indicated that Nur77 was upregulated in reperfused brain tissues. Genetic
      ablation of Nur77 reduced infarction area and promoted neuron survival under IR
      burden. Biochemical analysis demonstrated that Nur77 deletion protected
      mitochondrial function, attenuated mitochondrial oxidative stress, preserved
      mitochondrial potential, and blocked mitochondria-related cell apoptosis. In
      addition, we illustrated that Nur77 mediated mitochondrial damage via evoking
      mitochondrial fragmentation that occurred through increased mitochondrial fission
      and decreased fusion. Besides, our results also demonstrated that Nur77
      controlled mitochondrial fragmentation via upregulating INF2 in a manner
      dependent on the Wnt/beta-catenin pathway; inhibition of the Wnt pathway
      abrogated the protective effect of Nur77 deletion on reperfused-mediated neurons.
      Altogether, our study highlights that the pathogenesis of cerebral IR injury is
      associated with Nur77 activation followed by augmented mitochondrial
      fragmentation via an abnormal Wnt/beta-catenin/INF2 pathway. Accordingly, Nur77
      dependent mitochondrial fragmentation and the Wnt/beta-catenin/INF2 axis may
      represent novel therapeutic targets to reduce cerebral IR injury.

PMID- 30298451
TI  - Ion release, antimicrobial and physio-mechanical properties of glass ionomer
      cement containing micro or nanosized hexametaphosphate, and their effect on
      enamel demineralization.
AB  - OBJECTIVES: To evaluate the effects of hexametaphosphate microparticles (mHMP) or
      nanoparticles (nHMP) incorporated in glass ionomer cement (GIC) on antimicrobial
      and physico-mechanical properties, fluoride (F) release, and enamel
      demineralization. MATERIAL AND METHODS: HMP solutions were obtained at
      concentrations of 1, 3, 6, 9, and 12%, for screening of antimicrobial activity.
      Next, mHMP or nHMP at 6, 9, and 12% were incorporated into a resin-modified GIC
      and the antibacterial activity was evaluated. The resistance to diametral tensile
      and compressive strength, surface hardness, and degree of monomer conversion as
      well as F and HMP releases of GICs were determined. Furthermore, specimens were
      attached to enamel blocks and submitted to pH-cycling, and mineral loss was
      determined. Parametric and non-parametric tests were performed, after checking
      data homoscedasticity (p < 0.05). RESULTS: HMP solutions at 6, 9, and 12%
      demonstrated the best antibacterial activity. GIC containing HMP showed better
      antibacterial effects at 9 and 12% for nHMP. Regarding F and HMP releases, the
      highest levels of release occurred for groups containing 9 and 12% nHMP. With the
      increase in HMP concentration, there was lower mineral loss. However, the
      incorporation of mHMP or nHMP in GIC reduced values of physico-mechanical
      properties when compared to the control GIC. CONCLUSIONS: nHMP improves
      antimicrobial activity and fluoride release, and decreases enamel
      demineralization, but reduces the physico-mechanical properties of GIC. CLINICAL
      RELEVANCE: The association of GIC/HMP could be an alternative material for
      patients at high risk for dental caries and could be indicated for low-stress
      regions or provisional restorations.

PMID- 30298452
TI  - Long-term scopolamine treatment and dental caries.
AB  - OBJECTIVES: To investigate whether scopolamine, an anticholinergic agent which
      induces hyposalivation, represents a risk factor for the occurrence of dental
      caries. MATERIALS AND METHODS: A retrospective cohort study was carried out among
      sailors treated with scopolamine for seasickness. The study population included
      370 young healthy male adults (18-30 years old) who served in the Israel Navy
      between 2012 and 2016. Of these, 66 subjects who were chronically treated with
      intermittent administration of scopolamine, either by the oral or transdermal
      route, were assigned to the study group. Documented subject characteristics
      included age, socioeconomic status, level of education, body mass index, smoking
      history, and dental hygiene. Follow-up lasted 1 to 3.5 years. RESULTS: Two- to
      3.5-year follow-up revealed a higher risk of dental caries in 15 of 16 subjects
      (93.8%) treated with an average of 50.9 mg scopolamine, in contrast to only 71 of
      108 control subjects (65.7%) (RR = 1.43, p = 0.02 [95% CI = 1.18-1.72]). Follow
      up for 1-1.5 years revealed a lower occurrence of dental caries in both the study
      group (11/22, 50.0%) and the control group (46/104, 44.2%). Follow-up of 1.5-2
      years also revealed less dental caries, in 16/28 subjects (57.1%) in the study
      group and 51/92 subjects (55.4%) in the control group. The differences were not
      statistically significant. CONCLUSIONS: In healthy young adults, prolonged
      intermittent use of scopolamine was found to be a risk factor for the development
      of dental caries. CLINICAL SIGNIFICANCE: Dental care and hygiene should be
      intensified when administering hyposalivatory anticholinergic agents.

PMID- 30298453
TI  - Comparison of an indirect impression scanning system and two direct intraoral
      scanning systems in vivo.
AB  - OBJECTIVES: This in vivo study aimed to compare the marginal discrepancies of
      zirconia copings manufactured on the basis of two direct intraoral scanning
      systems and the indirect digitization of a conventional impression. MATERIALS AND
      METHODS: A total of 63 teeth in 23 patients were prepared to receive full
      coverage crowns. Subsequently, these teeth were intraorally scanned using CEREC
      AC Omnicam and Cara TRIOS and a conventional impression was taken with the
      scannable PVS Flexitime Fast & Scan. The conventional impression was then
      extraorally digitized using a D700 laboratory scanner. The zirconia copings were
      manufactured on the basis of the resulting datasets. Silicone replicas of the
      copings were produced and sectioned for the measurement of the marginal
      discrepancy under a digital microscope. RESULTS: The statistical analysis showed
      no significant differences between the two intraoral scanners, the CEREC AC
      Omnicam (86.09 MUm +/- 61.46 MUm) and the Cara TRIOS (88.95 MUm +/- 54.46 MUm).
      However, the discrepancies of the zirconia copings obtained from the laboratory
      scans of conventional impressions (143.29 MUm +/- 100.71 MUm) showed significant
      differences. Both intraoral scanners achieved a marginal discrepancy below 100
      MUm, whereas the laboratory scan exhibited considerably higher values.
      CONCLUSIONS: The intraoral scanners tested allow for the production of single
      tooth-restorations with an adequate marginal fit, whereas the production of
      restorations on the basis of the scan of a conventional impression led to vast
      marginal gaps. CLINICAL RELEVANCE: The method of digitizing a conventional
      impression using a laboratory scanner seemed to have reached its limits in the
      clinical environment.

PMID- 30298455
TI  - The effects of the timing of exposure to cadmium on the oviposition behavior of
      Drosophila melanogaster.
AB  - Animals can greatly increase their fitness by choosing oviposition sites free
      from damaging substances such as the heavy metal cadmium (Cd). Previous research
      has shown that Drosophila melanogaster reared on uncontaminated media lay fewer
      eggs on substrates containing Cd. In this study, we examined the effects of prior
      exposure to Cd on oviposition site preference. We tested flies that had been
      exposed to Cd continuously from egg to adult, only during pre-adult stages, or
      for the 4 days of adulthood prior to testing. We found that flies avoid laying
      eggs on Cd-contaminated medium and also that flies exposed to Cd as adults laid
      significantly fewer eggs than controls never exposed to Cd. We did not observe
      consistent changes in oviposition as a result of pre-adult exposure alone. Our
      results suggest that the presence of cadmium in the environment, even at low
      doses and for short periods of time during adulthood, can harm the fitness of
      Drosophila melanogaster.

PMID- 30298454
TI  - Are dairy products containing probiotics beneficial for oral health? A systematic
      review and meta-analysis.
AB  - OBJECTIVES: To evaluate the effect of probiotic containing in dairy products on
      oral and salivary parameters. MATERIAL AND METHODS: Electronic searches were
      performed based on the PICO criteria. Randomized controlled trials in
      adults/children (P) in which dairy products containing probiotics (I) were
      compared to controls (C) for establishment of oral health (O) were included. Risk
      of bias and data extraction were performed. The meta-analysis evaluated the
      influence of probiotics on Streptococcus mutans (SM), Lactobacillus spp. (LB),
      and yeast counts, plaque index, and salivary pH. Random or fixed effect models
      were used, and heterogeneity was tested. RESULTS: Thirty-two studies were
      included in the qualitative synthesis, and 24 in the meta-analysis. For
      dichotomous results, individuals who consumed probiotics exhibited decreased
      scores in SM concentrations (RD 0.15 [0.02, 0.28] p = 0.03, I2 = 70%), but no
      change was observed for LB (RD 0.10 [- 0.03, 0.23] p = 0.13, I2 = 94%), or yeast
      levels (RD 0.05 [- 0.02, 0.12] p = 0.7, I2 = 48%). For continuous analysis, both
      probiotic and control groups presented similar results for SM and LB (MD - 0.55 [
      1.16, 0.07] p = 0.08, I2 = 62%, and RD 0.10 [- 0.03, 0.23] p = 0.13, I2 = 94%,
      respectively). The consumption of probiotics increased salivary pH (MD 0.20
      [0.04, 0.35] p = 0.01, I2 = 46%) and plaque index (MD 0.38 [0.11, 0.65] p =
      0.005, I2 = 0%). The probiotic milk reduced SM (MD - 0.59 [- 0.96, - 0.22] p =
      0.002, I2 = 0%), and the probiotic yogurt decreased LB counts (RD 0.35 [0.19,
      0.51] p < 0.0001, I2 = 0%). CONCLUSIONS: In general, dairy probiotics were
      effective in reducing SM, increasing salivary pH, and promoting a higher plaque
      index. Liquid matrices, such as milk and yogurt, seem to be more effective in
      reducing SM and LB levels. CLINICAL RELEVANCE: Consumption of dairy products
      containing probiotics could be a supporting method in caries prevention.

PMID- 30298457
TI  - Irish Thoracic Society Annual Scientific Meeting 23rd and 24th November 2018
      Europa Hotel Belfast.

PMID- 30298456
TI  - Spatiotemporal parameters in sprinters with unilateral and bilateral transfemoral
      amputations and functional impairments.
AB  - PURPOSE: Although sprinters with unilateral (UTF) and bilateral transfemoral
      (BTF) amputations and functional impairments (FIs) without amputation were
      allocated into different classifications because of the recent revision of the
      International Paralympic Committee Athletics Rules and Regulations, it is unclear
      whether running mechanics differ among the three groups. The aim of this study
      was to investigate the differences in the spatiotemporal parameters of the three
      groups during 100-m sprint in official competitions. METHODS: Using publicly
      available Internet broadcasts, we analyzed 11 elite-level sprinters with UTF
      amputation, 4 sprinters with BTF amputation, and 5 sprinters with FI without
      amputation. The best personal times for nearly all individuals were included. For
      each sprinter's race, the average speed, step frequency, and step length were
      calculated using the number of steps in conjunction with the official race time.
      RESULTS: Although there were no significant differences in the average speed
      among the UTF, BTF, and FI groups (7.95 +/- 0.22, 7.90 +/- 0.42, and 7.93 +/-
      0.14 m/s, respectively, p = 0.87), those with BTF amputation showed significantly
      lower step frequency (UTF: 4.20 +/- 0.20 Hz, BTF: 3.71 +/- 0.32 Hz, FI: 4.20 +/-
      0.10 Hz, p < 0.05) and longer step length (UTF: 1.90 +/- 0.08 m, BTF: 2.14 +/-
      0.02 m, FI: 1.89 +/- 0.06 m, p < 0.05) than the other two groups. CONCLUSION:
      These results suggest that the step characteristics during sprinting are not the
      same among sprinters with UTF amputation, BTF amputations, or FI without
      amputations.

PMID- 30298458
TI  - Dual roles of mitochondrial fusion gene FZO1 in yeast age asymmetry and in
      longevity mediated by a novel ATG32-dependent retrograde response.
AB  - The replicative lifespan of the yeast Saccharomyces cerevisiae models the aging
      of stem cells. Age asymmetry between the mother and daughter cells is established
      during each cell division, such that the daughter retains the capacity for self
      renewal while this ability is diminished in the mother. The segregation of fully
      functional mitochondria to daughter cells is one mechanism that underlies this
      age asymmetry. In this study, we have examined the role of mitochondrial dynamics
      in this phenomenon. Mitochondrial dynamics involve the processes of fission and
      fusion. Out of the three fusion and three fission genes tested, we have found
      that only FZO1 is required for the segregation of fully-functional mitochondria
      to daughter cells and in the maintenance of age asymmetry as manifested in the
      potential of daughters for a full replicative lifespan despite its deterioration
      in their mothers. The quality of mitochondria is determined by their turnover,
      and we have also discovered that deletion of FZO1 reduces mitophagy.
      Mitochondrial dysfunction elicits a compensatory retrograde response that extends
      replicative lifespan. Typically, the dysfunction that triggers this response
      encompasses energy production. The disruption of mitochondrial dynamics by
      deletion of FZO1 also activates the retrograde response to extend replicative
      lifespan. We call this novel pathway the mitochondrial dynamics-associated
      retrograde response (MDARR) because it is distinct in the signal proximal to the
      mitochondrion that initiates it. Furthermore, the MDARR engages the mitophagy
      receptor Atg32 on the mitochondrial surface, and we propose that this is due to
      the accumulation of Atg32-Atg11-Dnm1 complexes on the mitochondrion in the
      absence of Fzo1 activity. MDARR can be masked by the operation of the 'classic'
      retrograde response.

PMID- 30298459
TI  - Longitudinal Comparison of the Effect of Gastric Bypass to Sleeve Gastrectomy on
      Liver Function in a Bariatric Cohort: Tehran Obesity Treatment Study (TOTS).
AB  - BACKGROUND: Patients with morbid obesity commonly have fatty liver disease and
      elevated liver enzymes. While surgery effectively induces weight loss, bariatric
      techniques may differ regarding liver function improvement. OBJECTIVES: To
      evaluate and compare the trends of liver function recovery after gastric bypass
      surgery (GB) with sleeve gastrectomy (SG). SETTING: University hospitals, Iran.
      METHODS: Adult bariatric candidates without a history of alcohol consumption or
      other etiologies of liver disease who underwent SG (n = 682) or GB (n = 355) were
      included. Trends of weight loss parameters and alanine transaminase (ALT),
      aspartate transaminase (AST), and alkaline phosphatase (ALP) at 0, 6 (in 90.4%),
      12 (in 83.5%), and 24 months (in 67.1%) were compared using generalized
      estimating equations method. RESULTS: Overall, 1037 patients with mean age of
      38.4 +/- 11.2 and mean body mass index of 44.9 +/- 6.2 kg/m2 were analyzed.
      Seventy-eight percent of patients had fatty liver by ultrasound. Both GB and SG
      patients lost significant weight, with GB patients having a higher percentage of
      excess weight loss at 24 months (80.1% vs. 75.9%, Pbetween-group = .008). SG
      patients showed more favorable trends in liver chemistries with significantly
      lower ALT at 12 months and AST and ALP levels at 6 and 12 months. However, the
      two groups were comparable at 24 months. Significantly more GB patients developed
      high ALT at 6 and high AST at 6 and 12 months. Undergoing GB was associated with
      smaller 0-12-month changes in ALT, AST, and ALP. CONCLUSIONS: Bariatric surgery
      resulted in improvement in liver function parameters, with SG showing advantages
      over GB in the first postoperative year.

PMID- 30298461
TI  - Caplacizumab: First Global Approval.
AB  - Ablynx, a Sanofi Company, has developed the anti-von Willebrand factor
      Nanobody(r) caplacizumab (CabliviTM) for the treatment of acquired thrombotic
      thrombocytopenic purpura (aTTP). Based on positive results in phase II and III
      trials in patients with aTTP, caplacizumab was recently approved in the EU for
      the treatment of adults experiencing an episode of aTTP, in conjunction with
      plasma exchange and immunosuppression. This article summarizes the milestones in
      the development of caplacizumab leading to this first approval.

PMID- 30298460
TI  - Low-ranking individuals present high and unstable fecal cortisol levels in
      provisioned free-ranging adult male rhesus macaques (Macaca mulatta) during the
      birth season in a mountain area of northern China.
AB  - Social hierarchy commonly exists in animal societies, affecting both the
      endocrine functioning and the behavior of animals. In nonhuman primates, the
      relationship between social rank and cortisol levels varies across species and
      even within species. Here, we assessed the relationships between social rank and
      fecal cortisol levels in adult male Taihangshan macaques (rhesus macaques, Macaca
      mulatta tcheliensis) from the provisioned, free-ranging Wulongkou-2 (WLK-2) group
      inhabiting Wulongkou Scenic Area, Jiyuan, China. From March to May 2014, we
      recorded 195 agonistic behaviors and collected 54 fresh fecal samples from eight
      adult male Taihangshan macaques. Males were assigned a social rank according to
      an agonistic behavior matrix, and enzyme-linked immunosorbent assay was then used
      to measure the cortisol concentration in the fecal samples. We found that social
      rank among the eight male Taihangshan macaques in WLK-2 group followed a strict
      linear hierarchy, and that fecal cortisol levels were significantly higher and
      more variable in low-ranking males than in more dominant individuals. Age was not
      significantly associated with social rank or fecal cortisol levels. Our results
      suggest that social rank and maintenance of the social hierarchy within the WLK-2
      group is a chronic stressor, with low-ranking males maintaining heightened stress
      levels and enlarged reactive scope relative to dominant males. This provides new
      support for the theory that social environment can influence endocrine
      functioning.

PMID- 30298462
TI  - Automatic Recognition of Posed Facial Expression of Emotion in Individuals with
      Autism Spectrum Disorder.
AB  - Facial expression is impaired in autism spectrum disorder (ASD), but rarely
      systematically studied. We focus on the ability of individuals with ASD to
      produce facial expressions of emotions in response to a verbal prompt. We used
      the Janssen Autism Knowledge Engine (JAKE(r)), including automated facial
      expression analysis software (FACET) to measure facial expressions in individuals
      with ASD (n = 144) and a typically developing (TD) comparison group (n = 41).
      Differences in ability to produce facial expressions were observed between ASD
      and TD groups, demonstrated by activation of facial action units (happy, scared,
      surprised, disgusted, but not angry or sad). Activation of facial action units
      correlated with parent-reported social communication skills. This approach has
      potential for diagnostic and response to intervention measures. Trial
      Registration NCT02299700.

PMID- 30298463
TI  - Everything has Its Time: Narrow Temporal Windows are Associated with High Levels
      of Autistic Traits Via Weaknesses in Multisensory Integration.
AB  - The present study examined whether fundamental sensory functions such as temporal
      processing and multisensory integration are related to autistic traits in the
      general population. Both a narrower temporal window (TW) for simultaneous
      perception, as measured by a temporal order judgement task, and a reduced ability
      to engage in multisensory integration during the sound-induced flash illusion
      task were related to higher levels of autistic traits. Additionally, a narrow TW
      is associated with high levels of autistic traits due to a deficiency in
      multisensory integration. Taken together, these findings suggest that alterations
      in fundamental functions produce a cascading effect on higher-order social and
      cognitive functions, such as those experienced by people with autism spectrum
      disorder.

PMID- 30298464
TI  - Beyond the Nuclear Family: Trends in Children Living in Shared Households.
AB  - Using data from the 1996-2008 panels of the Survey of Income and Program
      Participation and the 2009-2016 American Community Survey, we examine trends in
      U.S. children living in shared households (living with adults beyond their
      nuclear (parent/parent's partner/sibling) family). We find that although the
      share of children who lived in a shared household increased over this period, the
      rise was nearly entirely driven by an increase in three
      generation/multigenerational households (coresident grandparent(s), parent(s),
      and child). In 1996, 5.7 % of children lived in a three-generation household; by
      2016, 9.8 % did likewise-more than a 4 percentage point increase. More
      economically advantaged groups (older, more educated mothers, married households)
      experienced the largest percentage increase in three-generation coresidence,
      although correlates of coresidence remained largely stable. Decomposition
      analyses suggest that the rise in Social Security receipt and changes in parental
      relationship status (less marriage, more single parenthood) most strongly
      explained the increase in three-generation households. Given the dramatic rise in
      three-generation households, more research is needed to understand the
      consequences of these living arrangements for children, their parents, and their
      grandparents.

PMID- 30298465
TI  - Interstate Migration and Employer-to-Employer Transitions in the United States:
      New Evidence From Administrative Records Data.
AB  - Declines in migration across labor markets have prompted concerns that the U.S.
      economy is becoming less dynamic. In this study, we examine the relationship
      between residential migration and employer-to-employer transitions in the United
      States, using both survey and administrative records data. We first note strong
      disagreement between the Current Population Survey (CPS) and other migration
      statistics on the timing and severity of any decline in U.S. interstate
      migration. Despite these divergent patterns for overall residential migration, we
      find consistent evidence of a substantial decline in economic migration between
      2000 and 2010. We find that composition and the returns to migration have limited
      ability to explain recent changes in interstate migration.

PMID- 30298466
TI  - Saving, Sharing, or Spending? The Wealth Consequences of Raising Children.
AB  - This study uses 1986-2012 National Longitudinal Survey of Youth 1979 cohort data
      to investigate the relationship between raising children and net worth among
      younger Baby Boomer parents. I combine fixed-effects and unconditional quantile
      regression models to estimate changes in net worth associated with having
      children in different age groups across the wealth distribution. This allows me
      to test whether standard economic models for savings and consumption over the
      life course hold for families at different wealth levels. My findings show that
      the wealth effects of children vary throughout the distribution. Among families
      at or below the median, children of all ages were associated with wealth
      declines, likely due to the costs of child-rearing. However, at the 75th
      percentile and above, wealth increased with the presence of younger children but
      decreased after those children reached age 18. My results, therefore, provide
      evidence for a saving and investment model of child-rearing among wealthier
      families but not among families at or below median wealth levels. For these
      families, the costs of raising children largely outweighed motivations for
      saving.

PMID- 30298467
TI  - Recommendations by the Spanish Society of Hospital Pharmacy, the Spanish Society
      of Oncology Nursing and the Spanish Society of Medical Oncology for the safe
      management of antineoplastic medication in cancer patients.
AB  - AIM: To define recommendations that permit safe management of antineoplastic
      medication, minimise medication errors and improve the safety of cancer patients
      undergoing treatment. METHODS: By reviewing the literature and consulting the
      websites of various health organisations and agencies, an expert committee from
      the Spanish Society of Hospital Pharmacy and the Spanish Society of Medical
      Oncology defined a set of safe practices covering all stages of providing cancer
      therapy to patients. The Spanish Society of Oncology Nursing revised and endorsed
      the final list. RESULTS: In total, 68 recommendations arranged in five sections
      were defined. They include issues concerning the training of health
      professionals, the technological resources needed, treatment planning, informing
      the patient and his/her family, the processes of prescribing, preparing,
      dispensing and administering cancer therapy (orally, parenterally or
      intrathecally), assessing patient adherence and treatment toxicity. CONCLUSIONS:
      It is essential for healthcare establishments to implement specific measures
      designed to prevent medication errors, in order to ensure the safety of cancer
      patients treated with antineoplastic medication.

PMID- 30298468
TI  - Modulation of cancer cells' radiation response in the presence of folate
      conjugated Au@Fe2O3 nanocomplex as a targeted radiosensitizer.
AB  - OBJECTIVES: To investigate the effects of Au@Fe2O3 core-shell nanoparticle (NP),
      with and without conjugation to folic acid (FA) as a targeting ligand, on
      radiosensitization of both cancer and healthy cells. METHODS: Au@Fe2O3 NPs were
      first synthesized, then modified with FA, and finally characterized. Radiation
      dose enhancement studies were performed on KB cancer cells and L929 healthy
      cells. NPs at the concentration of 20 ug/ml were first incubated with both cell
      lines and then different doses of 6 MV X-ray radiation were examined. The end
      effects were evaluated via MTT assay and flow cytometry using AnnexinV/PI kit.
      RESULTS: It was indicated that viability of KB cells has a much lower rate than
      L929 cells when the cells were treated by {(FA-Au@Fe2O3) + (X-ray)} regimen. Cell
      viability was even decreased significantly when X-ray dose increased. Moreover,
      flow cytometry studies revealed that FA-targeted NPs induced higher level of
      apoptosis for KB cancer cells than L929 healthy cells. CONCLUSION: Our findings
      provide a new perspective on high ability of the synthesized FA-targeted Au@Fe2O3
      NPs which may be considered as an efficient radiosensitizer in the process of
      targeted radiation therapy of cancer.

PMID- 30298469
TI  - Predictive factors of the treatment outcome in patients with advanced biliary
      tract cancer receiving gemcitabine plus cisplatin as first-line chemotherapy.
AB  - BACKGROUND: Few studies have clearly identified the prognostic factors in
      patients with advanced biliary tract cancer (BTC) receiving gemcitabine plus
      cisplatin (GC) which is acknowledged as standard chemotherapy regimen.
      OBJECTIVES: The aim of this study was to identify predictive factors of the
      overall survival (OS) in advanced BTC patients receiving GC therapy. METHODS:
      Data of 307 patients with advanced BTC who received GC therapy as the first-line
      chemotherapy at our institution from January 2007 to June 2017 were reviewed
      retrospectively. The patients were randomly assigned to the investigation or the
      validation dataset at the ratio of 2:1. Multivariate analysis was conducted to
      identify the prognostic factors, a prognostic index is proposed from the
      investigation dataset, and the usefulness of this index was confirmed in the
      validation dataset. RESULTS: Multivariate analysis identified poor performance
      status, elevated serum lactate dehydrogenase, and elevated neutrophil-to
      lymphocyte ratio as independent unfavorable predictors. The patients could be
      classified into three groups according to these factors, and it was found that
      the outcomes differed significantly among the three groups (P = 0.0002, good- vs.
      intermediate-prognosis groups; P = 0.005, intermediate- vs. poor-prognosis
      groups). When this index was applied to the validation dataset, the OS was
      confirmed to differ significantly among the three groups (P = 0.04, good- vs.
      intermediate-prognosis groups, P < 0.0001, intermediate- vs. poor-prognosis
      groups). CONCLUSIONS: We identified three predictors of the OS in patients with
      advanced BTC receiving GC therapy in this study, based on which we could classify
      the patients into three risk groups.

PMID- 30298470
TI  - Diagnosis of nontuberculous mycobacterial disease in the era of surveillance
      chest CT scans.
AB  - The radiologic surveillance of smokers with low-dose CT scan has led to a
      significant surge of radiologic incidental findings, including the detection of
      early stages of pulmonary infections including nontuberculous mycobacteria (NTM).
      This causes a state of overdiagnosis and potential overtreatment of NTM lung
      disease. Here we propose a new approach to NTM pulmonary disease in the era of
      increased CT scanning.

PMID- 30298471
TI  - Inhaled corticosteroids and risk of upper respiratory tract infection in patients
      with asthma: a meta-analysis.
AB  - BACKGROUND: Recent studies have suggested a possible association between
      respiratory infection and the use of inhaled corticosteroids (ICS). We aimed to
      ascertain the risk of upper respiratory tract infection (URTI) with long-term
      inhaled corticosteroid use among patients with asthma. METHODS: Through a
      comprehensive literature search of PubMed, Cochrane Library, EMBASE, and Google
      Scholar from inception to May 2018, we included randomized controlled trials of
      any ICS vs. a control treatment for asthma, with reporting of URTI as an adverse
      event. We conducted meta-analyses by the Peto approaches to generate summary
      estimates comparing ICS with non-ICS treatment on the risk of URTI. RESULTS:
      Seventeen trials (15,336 subjects) were included. Compared with non-ICS
      treatment, ICSs were associated with a significantly increased risk of URTI (Peto
      OR, 1.24; 95% CI 1.08-1.42; I2 = 5%, p = 0.002). Subgroup analyses were performed
      for different dose, both high- and low-dose ICSs were associated with a
      significantly increased risk of URTI (high dose: Peto OR, 1.46; 95% CI 1.05-2.03;
      I2 = 0%; p = 0.03) (low dose: Peto OR, 1.20; 95% CI 1.04-1.39; I2 = 25%; p =
      0.01). Moreover, fluticasone was observed with an increased risk of URTI (Peto
      OR, 1.18; 95% CI 1.02-1.38; p = 0.03; heterogeneity: I2 = 21%) but not
      budesonide, low-dose fluticasone treatment was associated with a significantly
      higher risk of URTI but not high dose. CONCLUSIONS: This study raises safety
      concerns about the risk of URTI associated with ICS use in patients with asthma,
      but it should be further investigated.

PMID- 30298472
TI  - 18F-FDG PET/CT monitoring of non-tuberculous mycobacterial infection in a child
      with interleukin-12 receptor beta-1 deficiency.

PMID- 30298473
TI  - A phase III, open-label, single-arm, study to evaluate the safety and
      immunogenicity of a trivalent, surface antigen inactivated subunit influenza
      virus vaccine produced in mammalian cell culture (Optaflu(r)) in healthy adults.
AB  - Vaccination is an essential tool in reducing the impact of seasonal influenza
      infections. The viral strains responsible for seasonal outbreaks vary annually,
      and preventive vaccines have to be adapted accordingly. The aim of this study was
      to evaluate the safety, clinical tolerability and the antibody response to each
      of the three influenza vaccine antigens after vaccination with a cell-derived,
      trivalent, surface antigen, inactivated influenza vaccine (TIVc), as measured by
      single radial haemolysis (SRH) or haemagglutination inhibition (HI) assay in
      accordance with European Union licensing guidelines in place for years 2013/2014.
      This phase 3, open-label, single-arm study enrolled 126 healthy adults divided
      into two age groups (63 subjects aged 18 to <= 60 years and 63 subjects aged >=
      61 years). Antibody titres were measured before and 21 days after vaccination.
      Adverse events were determined using diary cards, interviews and reviews of the
      available medical records. One subject was lost to follow-up and three subjects
      had protocol deviations. Following vaccination, protective HI antibody titres (>=
      1:40) were detected in 100%, 97%, and 94% of the younger adults (18-<= 60 years)
      and in 97%, 95%, and 80% of the older adults (>= 61 years) against the A (H1N1),
      A (H3N2), and B influenza strains respectively. The antibody response licensing
      criteria were met in both age groups. Solicited adverse events were reported by
      57% subjects 18 to <= 60 years and 35% subjects >= 61 years. Among the younger
      adults 51% had local and 27% had systemic adverse events, whereas of the older
      subjects 29% had local and 13% had systemic adverse events (mainly injection site
      pain or headache in both age groups). Unsolicited adverse events at least
      possibly related to the vaccine were mild and detected in 3% of the younger
      adults and none of the older adults. Overall, the trivalent, surface antigen,
      inactivated subunit influenza virus vaccine produced in mammalian cell culture
      proved to be safe and immunogenic in younger and older healthy adults.

PMID- 30298474
TI  - Why is this Happening? A Brief Measure of Parental Attributions Assessing
      Parents' Intentionality, Permanence, and Dispositional Attributions of Their
      Child with Conduct Problems.
AB  - We present and evaluate a new self-report measure of parental attributions
      developed for assessing child causal and dispositional attributions in parenting
      interventions. The Parent Attribution Measure (PAM) ascribes attributions along
      first-order dimensions of intentionality, permanence, likeability, and
      disposition, and a higher-order Total Scale. The psychometric analyses involved
      participants drawn from populations of clinical (n = 318) and community-based
      families (n = 214) who completed questionnaires assessing parental attributions,
      parenting behaviours, parental depression, parental feelings about the child, and
      child behavioural problems. Confirmatory factor analysis indicated that a 3
      factor hierarchical structure provided a close fitting model. The model with
      intentionality, permanence, and disposition (consolidating likeability and
      disposition) dimensions as first-order factors grouped under a higher-order
      general factor was validated in independent samples and demonstrated sound
      psychometric properties. The PAM presents as a brief measure of parental
      attributions assessing parents' intentionality, permanence, and dispositional
      attributions of their child with conduct problems.

PMID- 30298475
TI  - Comparison of In Vitro Stereoselective Metabolism of Bupropion in Human, Monkey,
      Rat, and Mouse Liver Microsomes.
AB  - BACKGROUND AND OBJECTIVES: Bupropion is an atypical antidepressant and smoking
      cessation aid associated with wide intersubject variability. This study compared
      the formation kinetics of three phase I metabolites (hydroxybupropion,
      threohydrobupropion, and erythrohydrobupropion) in human, marmoset, rat, and
      mouse liver microsomes. The objective was to establish suitability and
      limitations  for subsequent use of nonclinical species to model bupropion central
      nervous system (CNS) disposition in humans. METHODS: Hepatic microsomal
      incubations were conducted separately for the R- and S-bupropion enantiomers, and
      the formation of enantiomer-specific metabolites was determined using LC-MS/MS.
      Intrinsic formation clearance (CLint) of metabolites across the four species was
      determined from the formation rate versus substrate concentration relationship.
      RESULTS: The total clearance of S-bupropion was higher than that of R-bupropion
      in monkey and human liver microsomes. The contribution of hydroxybupropion to the
      total racemic bupropion clearance was 38%, 62%, 17%, and 96% in human, monkey,
      rat, and mouse, respectively.  In the same species order, threohydrobupropion
      contributed 53%, 23%, 17%, and 3%, and erythrohydrobupropion contributed 9%, 14%,
      66%, and 1.3%, respectively, to racemic bupropion clearance. CONCLUSION: The
      results demonstrate that phase I metabolism in monkeys best approximates that
      observed in humans, and support the preferred use of this species to investigate
      possible pharmacokinetic factors that influence the CNS disposition of bupropion
      and contribute to its high intersubject variability.

PMID- 30298476
TI  - The Influence of Caffeine Supplementation on Resistance Exercise: A Review.
AB  - This paper aims to critically evaluate and thoroughly discuss the evidence on the
      topic of caffeine supplementation when performing resistance exercise, as well as
      provide practical guidelines for the ingestion of caffeine prior to resistance
      exercise. Based on the current evidence, it seems that caffeine increases both
      maximal strength and muscular endurance. Furthermore, power appears to be
      enhanced with caffeine supplementation, although this effect might, to a certain
      extent, be caffeine dose- and external load-dependent. A reduction in rating of
      perceived exertion (RPE) might contribute to the performance-enhancing effects of
      caffeine supplementation as some studies have observed decreases in RPE coupled
      with increases in performance following caffeine ingestion. However, the same
      does not seem to be the case for pain perception as there is evidence showing
      acute increases in resistance exercise performance without any significant
      effects of caffeine ingestion on pain perception. Some studies have reported that
      caffeine ingestion did not affect exercise-induced muscle damage, but that it
      might reduce perceived resistance exercise-induced delayed-onset muscle soreness;
      however, this needs to be explored further. There is some evidence that caffeine
      ingestion, compared with a placebo, may lead to greater increases in the
      production of testosterone and cortisol following resistance exercise. However,
      given that the acute changes in hormone levels seem to be weakly correlated with
      hallmark adaptations to resistance exercise, such as hypertrophy and increased
      muscular strength, these findings are likely of questionable practical
      significance. Although not without contrasting findings, the available evidence
      suggests that caffeine ingestion can lead to acute increases in blood pressure
      (primarily systolic), and thus caution is needed regarding caffeine
      supplementation among individuals with high blood pressure. In the vast majority
      of studies, caffeine was administered in capsule or powder forms, and therefore
      the effects of alternative forms of caffeine, such as chewing gums or mouth
      rinses, on resistance exercise performance remain unclear. The emerging evidence
      suggests that coffee might be at least equally ergogenic as caffeine alone when
      the caffeine dose is matched. Doses in the range of 3-9 mg.kg-1 seem to be
      adequate for eliciting an ergogenic effect when administered 60 min pre-exercise.
      In general, caffeine seems to be safe when taken in the recommended doses.
      However, at doses as high as 9 mg.kg-1 or higher, side effects such as insomnia
      might be more pronounced. It remains unclear whether habituation reduces the
      ergogenic benefits of caffeine on resistance exercise as no evidence exists for
      this type of exercise. Caution is needed when extrapolating these conclusions to
      females as the vast majority of studies involved only male participants.

PMID- 30298477
TI  - Modeling the Benefits of Cooperative Drafting: Is There an Optimal Strategy to
      Facilitate a Sub-2-Hour Marathon Performance?
AB  - BACKGROUND: During a race, competing cyclists often cooperate by alternating
      between leading and drafting positions. This approach allows them to maximize
      velocity by using the energy saved while drafting, a technique to reduce the
      overall drag by exploiting the leader's slipstream. We have argued that a similar
      cooperative drafting approach could benefit elite marathon runners in their quest
      for the sub-2-hour marathon. OBJECTIVE: Our aim was to model the effects of
      various cooperative drafting scenarios on marathon performance by applying the
      critical velocity concept for intermittent high-intensity running. METHODS: We
      used the physiological characteristics of the world's most elite long-distance
      runners and mathematically simulated the depletion and recovery of their distance
      capacity when running above and below their critical velocity throughout a
      marathon. RESULTS: Our simulations showed that with four of the most elite
      runners in the world, a 2:00:48 (h:min:s) marathon is possible, a whopping 2 min
      faster than the current world record. We also explored the possibility of a sub-2
      hour marathon using multiple runners with the physiological characteristics of
      Eliud Kipchoge, arguably the best marathon runner of our time. We found that a
      team of eight Kipchoge-like runners could break the sub-2-hour marathon barrier.
      CONCLUSION: In the context of cooperative drafting, we show that the best team
      strategy for improving marathon performance time can be optimized using a
      mathematical model that is based on the physiological characteristics of each
      athlete.

PMID- 30298478
TI  - Ankle Bracing is Effective for Primary and Secondary Prevention of Acute Ankle
      Injuries in Athletes: A Systematic Review and Meta-Analyses.
AB  - BACKGROUND: Ankle bracing has been verified as being effective for secondary
      prevention of ankle injuries. However, new studies have recently been published
      that are not included in previous meta-analyses. Furthermore, the effects of
      bracing for primary prevention of ankle injuries are still unclear. OBJECTIVE:
      The objective of this article was to systematically review the literature about
      the effectiveness of ankle bracing on primary and secondary prevention of acute
      ankle injuries in athletes. METHODS: We searched PubMed, EMBASE, SPORTDiscus,
      CINAHL, and PEDro databases for eligible articles until July 2018. Randomized
      controlled trials that studied ankle bracing vs. no intervention for athletes
      were included. Risk of bias was assessed with the Cochrane Risk of Bias tool.
      Meta-analyses were conducted to study the effect of ankle bracing for primary and
      secondary prevention of ankle injuries. The Grading of Recommendation Assessment,
      Development, and Evaluation method was used to determine the quality of evidence.
      RESULTS: We included six randomized controlled trials. Significant risk ratios of
      0.53 (95% confidence interval 0.32-0.88) and 0.37 (95% confidence interval 0.24
      0.58) were found in favor of ankle bracing vs. no ankle bracing for primary (low
      quality of evidence, I2 = 77%) and secondary prevention (moderate quality of
      evidence, I2 = 0%) of acute ankle injuries. Numbers needed to treat were 26 and
      12 for the primary and secondary prevention of acute ankle injuries. CONCLUSIONS:
      Ankle bracing is effective for primary and secondary prevention of acute ankle
      injuries among athletes. However, conclusions in regard to primary prevention
      should be drawn cautiously because of the low quality of evidence and significant
      heterogeneity.

PMID- 30298481
TI  - Dermatologic Conditions of the Early Post-Transplant Period in Hematopoietic Stem
      Cell Transplant Recipients.
AB  - Hematopoietic stem cell transplants (HSCTs) are used to treat a variety of
      conditions, including hematologic malignancies, bone marrow failure syndromes,
      and immunodeficiencies. Over 60,000 HSCTs are performed annually worldwide, and
      the numbers continue to increase. Indeed, as new conditioning regimens develop,
      more and more individuals, including those of older age, will be eligible for
      transplants. Nevertheless, although HSCTs are clearly a life-saving and necessary
      treatment for thousands of patients per year, there is still substantial
      morbidity and mortality associated with the procedure. Of note, skin eruptions in
      the post-HSCT period are frequent and often significantly reduce quality of life
      in recipients. Moreover, these cutaneous findings sometimes herald an underlying
      systemic condition, presenting possible opportunities for timelier intervention.
      Dermatologists therefore play a vital role in distinguishing life-threatening
      conditions from benign issues and prompting recognition of critical complications
      earlier in their course. This article aims to review the major dermatologic
      conditions occurring in the early post-HSCT period.

PMID- 30298480
TI  - Over 50 Years of Researching Force Profiles in Rowing: What Do We Know?
AB  - There has been substantial interest in the mechanisms underpinning the skilled
      movements of on-water rowing for more than 150 years. Contemporary attention from
      biomechanical research has focused on the important relationship between kinetics
      (such as force application at the oar) and performance. A range of
      instrumentation systems have been developed and used in both academic and applied
      training contexts to better understand this relationship. Both qualitative and
      quantitative analytical approaches have been used in conjunction with these
      instrumentation systems for observing differences in propulsive force patterns
      between rowers. Despite the use of these analytical approaches, there is still
      limited consensus surrounding which characteristics of force profiles are
      associated with better rowing performance. Newell's model of constraints is
      provided as a framework for understanding why this lack of clarity exists
      surrounding force profile characteristics and performance. Further to this,
      direction for further research is provided by a framework that outlines two main
      streams: (1) exploration of constraints and how they are related to force profile
      characteristics; and (2) after controlling for constraints, exploration of
      performance and how it is related to force profile characteristics. These two
      steps are sequential, with an understanding of constraints influencing how we
      understand the interaction of force profiles and performance.

PMID- 30298479
TI  - An Updated Systematic Review of Childhood Physical Activity Questionnaires.
AB  - BACKGROUND AND OBJECTIVE: This review is an update of a previous review published
      in 2010, and aims to summarize the available studies on the measurement
      properties of physical activity questionnaires for young people under the age of
      18 years. METHODS: Systematic literature searches were carried out using the
      online PubMed, EMBASE, and SPORTDiscus databases up to 2018. Articles had to
      evaluate at least one of the measurement properties of a questionnaire measuring
      at least the duration or frequency of children's physical activity, and be
      published in the English language. The standardized COnsensus-based Standards for
      the selection of health Measurement INstruments (COSMIN) checklist was used for
      the quality assessment of the studies. RESULTS: This review yielded 87 articles
      on 89 different questionnaires. Within the 87 articles, 162 studies were
      conducted: 103 studies assessed construct validity, 50 assessed test-retest
      reliability, and nine assessed measurement error. Of these studies, 38% were of
      poor methodological quality and 49% of fair methodological quality. A
      questionnaire with acceptable validity was found only for adolescents, i.e., the
      Greek version of the 3-Day Physical Activity Record. Questionnaires with
      acceptable test-retest reliability were found in all age categories, i.e.,
      preschoolers, children, and adolescents. CONCLUSION: Unfortunately, no
      questionnaires were identified with conclusive evidence for both acceptable
      validity and reliability, partly due to the low methodological quality of the
      studies. This evidence is urgently needed, as current research and practice are
      using physical activity questionnaires of unknown validity and reliability.
      Therefore, recommendations for high-quality studies on measurement properties of
      physical activity questionnaires were formulated in the discussion. PROSPERO
      REGISTRATION NUMBER: CRD42016038695.

PMID- 30298482
TI  - [Analysis of audiological characteristics and genetic background in patients with
      nonsyndromic deafness and mitochondrial DNA 1555A>G mutation].
AB  - OBJECTIVE: To analyze the audiological features and genetic background of
      patients carrying mitochondrial DNA(mtDNA) 1555A>G mutation and factors which may
      influence the extent of nonsyndromic hearing loss associated with the mutation.
      METHODS: A literature search was carried out on databases including PubMed, CNKI,
      Wanfang, and VIP. Combined with author's data, the clinical features of the
      patients, in particular audiological characteristics, were summarized. RESULTS: A
      total of 857 effective cases were collected and analyzed. A significantly
      correlation was identified between history of aminoglycosides exposure and extent
      of hearing loss, in addition with a negative correlation between the age of onset
      and extent of hearing-impairment. Drug exposure was corelated with the age of
      onset but independent to the loss of high-frequency hearing loss. Heteroplasmies
      had a reverse correlation with the degree of hearing loss. Among the haplotypes
      of mitochondrial DNA, haplotype D was the most common one, while haplotype B had
      the highest penetrance. CONCLUSION: Nonsyndromic hearing loss associated with
      mitochondrial DNA 1555A>G mutation is influenced by factors such as
      aminoglycosides exposure, age, proportion of mutation, and haplotype of the
      mitochondrial DNA. Analysis of clinical cases is critical for identifying
      individuals carrying deafness susceptibility mutations and is the first step for
      early diagnosis.

PMID- 30298483
TI  - [Analysis of mutations of 4 common genes among 216 patients with non-syndromic
      hearing impairment].
AB  - OBJECTIVE: To explore the characteristics of mutations 4 common deafness-related
      genes among 216 patients from Shanghai area with non-syndromic hearing impairment
      (NSHI). METHODS: Thirteen mutation sites in the four genes, namely GJB2
      (c.35delG, c.176del16, c.235delC, c.299delAT, and c.155delTCTG), SLC26A4 (c.IVS7
      2A>G, c.2168A>G, and c.1229C>T), mtDNA 12SrRNA (m.1494C>T, m.1555A>G, m.7445A>G,
      and m.12201T>C) and GJB3 (c.538C>T) were detected among the 216 patients and 41
      individuals with normal hearing. The frequency and types of mutations were
      compared between the two groups. RESULTS: Among the 216 NSHI patients, the total
      detection rate was 16.20% (35/216). GJB2 mutations were found in 17(7.87%) of the
      216 patients, which included 5 cases with homozygous c.235delC mutation, 5 with
      homozygous c.235delC mutation, 1 with homozygous c.299delAT mutation, and 1 with
      homozygous c.299delAT mutation. c.235delC and 299delAT mutations were found in 5
      cases. SLC26A4 mutation was found in 12(5.56%) of the 216 patients, which
      included 2 cases with homozygous c.IVS7-2A>G mutation, 9 with homozygous c.IVS7
      2A>G mutation, and 1 with homozygous c.2168A>G mutation. Homogeneous mtDNA
      12SrRNA m.1555A>G mutation was found in 6(2.78%) of the 216 patients. No GJB3
      gene mutation was detected. No mutation of the 4 genes were detected in the 41
      individuals with normal hearing. In 2 cases of the 12 patients with SLC26A4 gene
      mutation, CT scan of the temporal bone has confirmed expansion of vestibular
      aqueduct. CONCLUSION: Above results indicated that GJB2 and SLC26A4 were the
      major genes involved with hearing loss in Shanghai area.

PMID- 30298484
TI  - [Genetic analysis of 100 fetuses with cleft lip with or without palate].
AB  - OBJECTIVE: To explore the genetic basis for fetuses with cleft lip and palate.
      METHODS: For 100 fetuses diagnosed with cleft lip with or without palate, G
      banding chromosomal karyotyping and copy number variation sequencing (CNV-seq)
      were carried out on chorionic villi, amniotic fluid or cordocentesis samples.
      RESULTS: No genomic abnormality was found among 49 fetuses with isolated cleft
      lip and palate, while 12 genomic aberrations were found among 51 fetuses with
      syndromic cleft lip and palate, which included 4 cases with trisomy 13, 2 cases
      with trisomy 18, 1 with X chromosome aneuploidy, 2 with other chromosomal
      aneuploidies and 3 with pathogenic CNVs. CONCLUSION: The incidence of genomic
      abnormalities in fetuses with cleft lip and palate was high. In addition to
      chromosomal abnormalities, attention should also be paid to pathogenic CNVs.

PMID- 30298485
TI  - [Mutation analysis of four pedigrees affected with hypophosphatemic rickets
      through targeted next-generation sequencing].
AB  - OBJECTIVE: To detect potential mutations of PHEX gene in four pedigrees affected
      with hypophosphatemic rickets (HR) and provide prenatal diagnosis for a fetus at
      13th gestational week. METHODS: The coding regions and exon/intron boundaries of
      PHEX, FGF23, DMP1, ENPP1, CLCN5 and SLC34A3 genes of the probands were analyzed
      by targeted next-generation sequencing (NGS). Suspected mutations were verified
      by Sanger sequencing among unaffected relatives and 200 unrelated healthy
      individuals. Deletions were confirmed by multiplex ligation-dependent probe
      amplification (MLPA) detection of probands, unaffected relatives and 20 unrelated
      healthy individuals. Prenatal diagnosis for a fetus with high risk was carried
      out through MLPA analysis. RESULTS: Four PHEX mutations were respectively
      detected in the pedigrees, which included c.850-3C>G, exon 11 deletion, exon 13
      deletion and c.1753G>A (p.G585R). Among these, exon 11 deletion, exon 13 deletion
      and c.1753G>A (p.G585R) were novel mutations and not found among unaffected
      relatives and healthy controls. In pedigree 3, the same mutation was not found in
      the fetus. CONCLUSION: Mutations of the PHEX gene probably underlies the disease
      among the four pedigrees. NGS combined with Sanger sequencing and/or MLPA
      detection can ensure accurate diagnosis for this disease.

PMID- 30298486
TI  - [Analysis of PHEX gene mutations in three pedigrees affected with
      hypophosphatemic rickets].
AB  - OBJECTIVE: To explore the molecular basis for three pedigrees affected with
      hypophosphatemia vitamin D resistant rickets (X-linked hypophosphatemia, XLH).
      METHODS: Peripheral blood samples from the three pedigrees were collected.
      Following DNA extraction, the 11 exons and flanking regions of the PHEX gene were
      subjected to PCR amplification and direct sequencing. Pathogenicity of identified
      mutations was evaluated through genotype-phenotype correlation. RESULTS: For
      pedigrees 1 and 2, pathogenic mutations were respectively identified in exon 8
      (c.871C>T, p.R291X) and exon 15 (c.1601C>T, p.P534L) of the PHEX gene. For
      pedigree 3, a novel mutation (c.1234delA, p.S412Vfs*12) was found in exon 11 of
      the PHEX gene, which caused shift the reading frame and premature termination of
      protein translation. CONCLUSION: The three mutations probably account for the XLH
      in the affected pedigrees. The discovery of novel mutations has enriched the
      spectrum of PHEX gene mutations.

PMID- 30298487
TI  - [Study of RET proto-oncogene mutations in two pedigrees affected with multiple
      endocrine neoplasia type 2A].
AB  - OBJECTIVE: To study the pattern of RET proto-oncogene mutations in two pedigrees
      affected with multiple endocrine neoplasia type 2A (MEN2A). METHODS: Peripheral
      blood samples were collected from members of the two pedigrees, with total
      genomic DNA extracted for polymerase chain reaction (PCR). PCR products of 7
      exons of the RET proto-oncogene (including exons 8, 10, 11, 13, 14, 15, 16) which
      have higher mutation rates were purified and subjected to direct sequencing.
      Suspected mutations in the 2 probands were verified in other members of the
      pedigrees. To exclude other mutations, PCR products of remaining 14 exons were
      sequenced in the proband from pedigree 1. RESULTS: A novel heterozygous mutation,
      1893-1895delCGA, was detected in exon 11 of the RET proto-oncogene among 3
      patients and 2 unaffected members from pedigree 1, while a heterozygous mutation,
      Cys634Arg, was detected in exon 11 among 2 patients and 1 unaffected family
      member from pedigree 2. CONCLUSION: The heterozygous 1893-1895delCGA and
      Cys634Arg mutations of the RET proto-oncogene probably underlie the disease in
      the two pedigrees. Above discovery has enriched the human gene mutation database.

PMID- 30298488
TI  - [Genetic screening and prenatal diagnosis for high risk families of Fragile X
      syndrome].
AB  - OBJECTIVE: To assess the value of genetic testing for Fragile X syndrome (FXS).
      METHODS: A domestically made diagnostic kit based Tri-primer-PCR method was used
      to detect mutations of the FMR1 gene among 6 pedigrees with unexplained
      intellectual disability. The results were verified by methylation PCR and
      Southern blotting. RESULTS: Pedigrees 1 and 6 were positive for the screening. In
      pedigree 1, a full-mutation allele with methylation was identified in the proband
      and his mother, which was passed on to the fetus. In pedigree 6, the proband was
      mosaic for a full-mutation allele and a pre-mutation allele. His sister was
      asymptomatic with a full-mutation. His mother carried pre-mutation allele, while
      his father and sister's baby were normal. The number of CGG repeats of the
      pedigrees 2 to 5 were in the normal range. CONCLUSION: Genetic testing can
      provide an effective way to prevent FXS caused by FMR1 mutations and enable
      prenatal diagnosis for families with a high risk for the disease.

PMID- 30298489
TI  - [Analysis of GCDH gene mutations in 3 patients from Fujian area with glutaric
      academia type I].
AB  - OBJECTIVE: To explore clinical features and mutation types in patients from
      Fujian area with glutaric academia type I(GA I). METHODS: Serum acylcarnitine and
      urine organic acid of 3 patients were determined with tandem mass spectrometry
      and gas chromatographic mass spectrometry. The patients also underwent magnetic
      resonance imaging analysis for the cranial region. Genomic DNA was extracted from
      peripheral blood samples, and the 12 exons and flanking regions of the GCDH gene
      were amplified with PCR and subjected to direct DNA sequencing. One hundred
      healthy newborns were used as controls. RESULTS: Mutations of the GCDH gene were
      identified in all of the 3 patients. Two patients have carried compound
      heterozygous mutations including c.1244-2A>C and c.1147C>T(p.R383C),
      c.406G>T(p.G136C) and c.1169G>A(p.G390E), respectively. One has carried
      homozygous c.1244-2A>C mutation. The same mutations were not detected among the
      100 healthy newborns. Only one patient received early intervention and did not
      develop the disease. The other two had irreversible damagesto their intelligence.
      CONCLUSION: c.1169G>A(p.G390E) is likely pathogenic mutations for GA I patients
      from Fujianarea. Early screening of neonatal metabolic diseases is crucial for
      such patients.

PMID- 30298490
TI  - [Differential expression and bioinformatics analysis of microRNA in peripheral
      blood mononuclear cells from patients with aplastic anemia].
AB  - OBJECTIVE: To study differential expression of microRNA (miRNA) in peripheral
      blood mononuclear cells (PBMNC) from patients with different types of aplastic
      anemia (AA) and explore the role of miRNA in the pathogenesis of AA. METHODS:
      miRNA microarray were used to determine the differential expression profile of
      miRNA in PBMNC from patients with AA. Real-time quantitative polymerase china
      reaction (RQ-PCR) was used to verify the differential expression of miRNA.
      Candidate miRNA were analyzed with bioinformatics tools. RESULTS: Compared with
      the normal controls, 6 miRNAs were up-regulated and 10 were down-regulated in
      patients with severe aplastic anemia (SAA), while 24 miRNAs were up-regulated and
      12 were down-regulated in patients with chronic non-severe aplastic anemia (CAA).
      Compared with CAA patients, 4 miRNAs were up-regulated and 11 were down-regulated
      in SAA patients. Compared with normal controls, 3 miRNAs were up-regulated and 4
      were down-regulated in both SAA and CAA patients. As verified by RQ-PCR,
      expression of miR-155-5p and miR-1260b were increased in both CAA and SAA
      patients compared with the normal controls (P<0.01). The expression of miR-155-5p
      and miR-1260b of CAA patients were higher than that of SAA patients (P<0.01).
      Bioinformatics analysis showed that target genes of miR-155-5p and miR-1260b may
      be involved in regulation of cell metabolism, gene expression and transcription,
      TNF signaling pathway, B cell receptor signaling pathway, Fc gamma R-mediated
      phagocytosis and other signaling process. CONCLUSION: There are characteristic
      differential expression profiles of miRNA in PBMNC from CAA and SAA patients, in
      which miRNA-155-5p and miRNA-1260b are both up-regulated. The common target gene
      predicted for miRNA-155-5p and miRNA-1260b is ETS1. miRNA-155-5p and miRNA-1260b
      may act synergistically to inhibit the expression of ETS1 and promote
      differentiation of Th17, therefore play an important role in the pathogenesis of
      AA.

PMID- 30298491
TI  - [Analysis of genotype-phenotype correlation for a novel MYH7-D554Y mutation
      identified in an ethnic Han Chinese pedigree affected with hypertrophic
      cardiomyopathy].
AB  - OBJECTIVE: To explore the genotype-phenotype correlation of a MYH7-D554Y mutation
      identified in an ethnic Han Chinese pedigree affected with hypertrophic
      cardiomyopathy. METHODS: Ninety six cardiovascular disease-related genes were
      detected in the proband by exonic amplification and high-throughput sequencing.
      Suspected mutations were verified by Sanger sequencing among 300 healthy controls
      as well as family members of the proband. The pathogenicity and conservation of
      the detected mutations were analyzed with ClustalX, MutationTaster, PolyPhen-2,
      Provean and SIFT software. RESULTS: Four of the 5 first-degree relatives of the
      proband were diagnosed with hypertrophic cardiomyopathy. The proband has featured
      extremely hypertrophic left ventricular wall with a maximal thickness of 35 mm.
      Genetic testing showed that four of them have carried a heterozygous c.1660G>T
      (p.Asp554Tyr) mutation of the MYH7 gene, who the remaining one was phenotypically
      normal and did not carry the mutation. The mutation has not been recorded by the
      Human Gene Mutation Database (HGMD) and other databases. Bioinformatics analysis
      suggested that the mutation site is highly conserved and that the mutation is
      pathogenic. CONCLUSION: The p.Asp554Tyr mutation of the MYH7 gene probably
      underlies the hypertrophic cardiomyopathy in this pedigree.

PMID- 30298492
TI  - [Analysis of TGFBI gene mutation in a pedigree affected with corneal dystrophy].
AB  - OBJECTIVE: To detect potential mutation in a large Chinese pedigree affected with
      congenital corneal dystrophy. METHODS: Two patients from the pedigree were
      subjected to whole exome sequencing to determine the candidate gene. Suspected
      mutation was verified in 13 additional members by directional Sanger sequencing.
      Ccorrelation between genotype and phenotype was explored. RESULTS: A missense
      mutation, c.1877A>C (p.His626Pro), was detected in exon 14 of the TGFBI gene in 8
      patients from the pedigree, but not in five unaffected members and 100 unrelated
      healthy controls. Respectively, the mutation was predicted as "affecting protein
      function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and
      MutationTaster. CONCLUSION: The c.1877A>C mutation of the TGFBI gene probably
      underlies the disease in this pedigree.

PMID- 30298493
TI  - [Analysis of clinical phenotypes and KCNJ2 gene mutations in a Chinese pedigree
      affected with Andersen-Tawil syndrome].
AB  - OBJECTIVE: To analyze the clinical phenotypes of a pedigree affected with
      periodic paralysis and explore its molecular basis. METHODS: Clinical data and
      peripheral blood samples of the pedigree were collected. The proband and his
      father both complained of periodic paralysis and dysmorphic features. The exome
      of the proband was screened using Roche NimbleGen probes, and the results were
      confirmed by Sanger sequencing. Suspected mutations were subjected to
      bioinformatic and gene-disease correlation analysis. RESULTS: A c.653G>A
      (p.R218Q) mutation of the KCNJ2 gene was detected in both the proband and his
      father. Bioinformatics analysis suggested it to be pathogenic. CONCLUSION: The
      clinical manifestation of the pedigree was suggestive of Andersen-Tawil syndrome.
      KCNJ2 c.653G>A (p.R218Q) was the pathogenic mutation in this pedigree.

PMID- 30298494
TI  - [Mutation analysis and prenatal diagnosis for a pedigree affected with maple
      syrup urine disease].
AB  - OBJECTIVE: To carry out mutation analysis for a pedigree affected with maple
      syrup urine disease (MSUD). METHODS: Clinical data of the proband was collected.
      Potential mutations of the BCKDHA and BCKDHB genes were analyzed by PCR and
      Sanger sequencing. Prenatal diagnosis was provided to a high-risk fetus at 12th
      gestational week through chorionic villus sampling. RESULTS: Two heterozygous
      mutations c.284G>C (p.Gly95Ala) and c.853C>T (p.Arg285*) of the BCKDHB gene were
      identified in the proband, which were inherited from his mother and father,
      respectively. Among these, c.853C>T (p.Arg285*) was known to be pathogenic, while
      c.284G>C (p.Gly95Ala) was a novel mutation. Prenatal diagnosis showed that the
      fetus has inherited the c.284G>C (p.Gly95Ala) mutation from its mother but no
      mutation from its father. After birth, the infant appeared to be healthy.
      CONCLUSION: The compound heterozygous mutations c.284G>C (p.Gly95Ala) and
      c.853C>T (p.Arg285*) probably underlie the pathogenesis of MUSD in the proband.
      Mutation analysis can facilitate prenatal diagnosis and genetic counseling for
      the affected families.

PMID- 30298495
TI  - [Analysis of TCOF1 mutation in a Chinese patient with Treacher-Collins syndrome].
AB  - OBJECTIVE: To detect potential mutation of TCOF1 gene in a Chinese family
      affected with Treacher-Collins syndrome. METHODS: Clinical data of the patient
      was collected. The analysis included history taking, clinical examination and
      genetic testing. All coding regions of the TCOF1 gene were subjected to PCR
      amplification and Sanger sequencing. RESULTS: A novel mutation c.2261ins G
      (p.E95X) of the TCOF1 gene was discovered in the patient. The same mutation was
      not found in his parents and 100 healthy controls. CONCLUSION: The c.2261insG
      (p.E95X) mutation of the TCOF1 gene probably underlies the disease in the
      patient. Genetic testing can facilitate diagnosis and genetic counseling for
      families affected with TCS.

PMID- 30298496
TI  - [Clinical and genetic analysis of a family affected by progressive familial
      intraphepatic cholestasis type 3].
AB  - OBJECTIVE: To explore the clinical and genetic characteristics of a family
      affected by genetic cholestasis. METHODS: Clinical data of the patient was
      collected. Targeted exome sequencing was carried out to detect the pathogenic
      mutations. The results were confirmed by Sanger sequencing. RESULTS: The patient,
      a 5-year-old boy, presented with severe cholestatic cirrhosis. Genetic analysis
      revealed that he has carried compound heterozygous mutations c.1006-2A>G and
      c.3580C>T (p.R1194X) of the ABCB4 gene, which were inherited from his father and
      mother, respectively. By structural prediction, the mutation c.3580C>T can give
      rise to a truncated multi-drug resistance protein 3 (MDR3). CONCLUSION: The
      patient was diagnosed with progressive familial intrahepatic cholestasis type 3
      (PFIC-3) based on clinical and molecular findings. Detection of novel mutations
      of the ABCB4 gene has provided valuable clues for the diagnosis and genetic
      counseling.

PMID- 30298497
TI  - [A case of congenital bile acid synthesis disorder type 2 and literature review].
AB  - OBJECTIVE: To summarize the clinical features, biochemical change and genetic
      mutations of a neonate with congenital bile acid synthesis disorder type 2.
      METHODS: Clinical features, blood biochemical index, gene analysis and treatment
      of the patient were reviewed. RESULTS: The patient presented with the symptoms of
      jaundice 3 days after birth but without skin itching. Pale stool was noted.
      Subsequently, he presented with hepatomegaly, blood coagulation disorders, left
      cochlear nerve damage, liver cirrhosis and remarkable growth retardation. Serum
      biochemistries showed that bilirubin and transaminase were elevated, while gamma 
      GT and total bile acid was normal. Abdominal ultrasonography indicated decline of
      gallbladder contraction. Cholangiography showed normal extra- and intrahepatic
      bile ducts and patent biliary tract. Liver biopsy showed intrahepatic
      cholestasis. Gene testing has identified a homozygous mutation in AKR1D1 gene.
      CONCLUSION: Congenital bile acid synthesis disorder should be suspected when a
      neonate has presented with jaundice, elevated bilirubin and transaminase, normal
      or reduced TBA and gamma -GT. Genetic testing and urine mass spectrometry
      analysis can diagnose congenital bile acid synthesis disorder. Early therapy is
      crucial to patients with congenital bile acid synthesis disorder.

PMID- 30298498
TI  - [Clinical and genetic analysis of a case with atypical ethyl malonate
      encephalopathy].
AB  - OBJECTIVE: To delineate the clinical and genetic characteristics of a girl
      featuring motor retardation, language retardation and regression, and light
      persisting diarrhea. METHODS: The patient was clinically examined and tested by
      tandem mass spectrometry and next generation sequencing. RESULTS: The proband
      could not stand and walk alone, and had light persisting diarrhea. She manifested
      language development retardation and regression. Laboratory tests were all
      normal, but the screening of metabolic disorders for urine and blood showed
      deficiency of short chain coenzyme A dehydrogenase due to elevated ethylmalonic
      acid and butyryl carnitine. By next generation sequencing, two compound
      heterozygous mutations of the ETHE1 gene, c.2T>A and c.488G>A, were discovered in
      the proband, which were respectively inherited from her father and mother.
      Bioinformatics analysis predicted both mutations to be pathogenic. The patient
      was diagnosed with ethylmalonic encephalopathy. Vitamin B1, B2, Coenzyme Q10, and
      L-carnitine were prescribed. The patient deteriorated and required liver
      transplantation at 4-year-1-month. CONCLUSION: Based on the clinical and genetic
      analysis, the proband was diagnosed with ethylmalonic encephalopathy caused by
      ETHE1 gene mutation. Next generation sequencing has provided a powerful tool for
      the diagnosis of such disorders.

PMID- 30298499
TI  - [A classic case with maple syrup urine disease caused by compound heterozygous
      mutations of BCKDHB gene].
AB  - OBJECTIVE: To explore the genetic etiology of a patient with classic maple syrup
      urine disease (MSUD). METHODS: Next-generation sequencing (NGS) was used to
      screen the exons of BCKDHA, BCKDHB, DBT and DLD genes. Suspected mutations were
      verified by Sanger sequencing. Bioinformatic analysis was carried out to predict
      the influence of mutations on the protein structure and function. RESULTS: NGS
      and Sanger sequencing have detected a c.550delT mutation in exon 5 of the BCKDHB
      gene in the mother and a c.1046G>A mutation in exon 10 of the BCKDHB gene in the
      father, while no mutation was found with BCKDHA, DBT and DLD genes. Among these,
      the c.550delT is a novel mutation. Bioinformatic analysis suggested that the two
      mutations both located in a highly conserved region and may decrease the activity
      of branched-chain alpha-ketoacid dehydrogenase complex through alternation of its
      structure. CONCLUSION: The compound heterozygous mutations c.550delT and
      c.1046G>A of the BCKDHB gene probably underlie the clinical manifestations of the
      patient with classic MSUD.

PMID- 30298500
TI  - [Analysis of SPTA1 gene mutations in a patient with hereditary elliptocytosis].
AB  - OBJECTIVE: To detect disease-causing mutations in a patient with hereditary
      elliptocytosis. METHODS: Sodium dodecyl sulfate polyacrylamide gel
      electropheresis (SDS-PAGE) was used to identify the type of erythrocyte membrane
      protein defect. Potential mutations of the exons and adjacent introns of relevant
      genes were analyzed by Sanger sequencing. RESULTS: SDS-PAGE has failed to detect
      any difference between the patient and healthy controls. However, Sanger
      sequencing has detected three mutations in the SPTA1 gene in the patient, which
      included c.5077A>C (p.Lys1693Gln) missense mutation in exon 36, c.5572C>G
      (p.Leu1858Val) missense mutation in exon 40, and a IVS45nt-12C>T in intron 45.
      The father and grandmother of the patient were both heterozygous for c.5077A>C
      mutation, while her mother was heterozygous for c.5572C>G and IVS45nt-12C>T
      mutations. CONCLUSION: The hereditary elliptocytosis in the patient may be
      attributed to the synergistic action of c.5077A>C, c.5572C>G and IVS45nt-12C>T
      mutations of the SPTA1 gene.

PMID- 30298501
TI  - [Clinical features and genetic analysis of a case with Coffin-Siris syndrome].
AB  - OBJECTIVE: To explore the clinical features and genomic abnormality of a patient
      with Coffin-Siris syndrome. METHODS: Microdeletion and microduplication were
      detected with chromosomal microarray analysis (CMA) and verified with real-time
      quantitative PCR. RESULTS: The patient, a 6-month-old boy, featured global
      development delay, thick eyebrows, low frontal hairline, long eyelash, flat nasal
      bridge, hypotonia, difficulty in turning over, over stretching of head, and
      hypoplatic nails. He could not stand stability or actively grasp. He also has
      characteristics of rickets. Chromosome karyotype of the patient was normal.
      Genomic analysis has detected a 1.3 Mb deletion in 6q25.3 region encompassing the
      ARID1B gene. Neither of his parents was found to harbor the same deletion.
      CONCLUSION: The 6q25.3 microdeletion probably underlies the Coffin-Siris syndrome
      in this patient, and rickets may be part of its clinical spectrum.

PMID- 30298502
TI  - [Prenatal diagnosis and genetic analysis of a fetus with 2p13.3-p12
      microdeletion].
AB  - OBJECTIVE: To provide prenatal diagnosis for a pregnant woman with a history of
      Williams-Beuren syndrome pregnancy. METHODS: The karyotypes of the fetus and his
      parents were analyzed with routine G-banding. Their genomic DNA was also analyzed
      with array comparative genomic hybridization (aCGH). RESULTS: No karyotypic
      abnormality was detected for the fetus and his parents. aCGH has identified a de
      novo 5.09 Mb deletion at 2p13.3-p12 in the fetus. CONCLUSION: The 2p13.3-p12
      microdeletion carried by the fetus was de novo. As it has involved dosage
      sensitive genes SPR and DCTN1, the deletion is probably pathogenic.

PMID- 30298503
TI  - [Identification of a novel duplication of Xq13.1 in a case with floppy infant
      syndrome with SNP-array].
AB  - OBJECTIVE: To explore the candidate disease causing gene for a case with floppy
      infant syndrome (FIS). METHODS: Single nucleotide polymorphism array (SNP array)
      was used for analyzing the whole genome copy number mutations in the proband.
      Multiple PCR combined with denaturing high performance liquid chromatography
      (DHPLC) was employed to verify the suspected mutations in the proband and his
      family members. RESULTS: A large duplication arr [hg19] Xq13.1: 67 987 646-73 805
      828, which spans approximately 5.818182 Mb and encompasses 66 known genes, was
      identified in the proband. The multiple PCR-DHPLC assay confirmed duplication of
      HDAC8, PHKA1, TAF1, DLG3, KIF4A, IGBP1, PJA1 and SLC16A2 genes in the proband.
      His mother and grandmother both had duplication of the above genes in one X
      chromosome, but his aunt had not. CONCLUSION: The large Xq13.1 duplication
      identified by the SNP array probably underlies the FIS in this family. For its
      high-throughput, high resolution and capacity of automation, SNP array has
      provided a first line method for the genetic testing for infants featuring
      developmental delay with unknown reason, mental retardation, autism, multiple
      malformation and FIS.

PMID- 30298504
TI  - [Genetic analysis of a fetus with partial 18p tetraploidy syndrome].
AB  - OBJECTIVE: To analyze a fetus with abnormal cardiac ultrasound by using various
      techniques and explore its genotype-phenotype correlation. METHODS: Lymphocytes
      derived from umbilical cord blood sample were subjected to G-banding analysis.
      Short tandem repeats quantitative fluorescence PCR (STR-QF-PCR) was used for
      analysis of fetal DNA as an auxiliary test. Low-coverage whole genome sequencing
      (WGS) was used to detect chromosomal deletion/duplication which exceeded 100 kb
      in size. RESULTS: The karyotype of the fetus was 47,XN,+mar. As detected by STR
      QF-PCR, the copy number of GATA178F11 locus on chromosome 18 was 4, and the
      duplicated fragment was derived from the mother. WGS suggested that the fetus to
      be 46,XN,dup(18p11.21p11.32).seq [GRCh37/hg19](10 001-15 378 887)* 4, with the
      duplicated fragment spanning approximately 15.38 Mb. CONCLUSION: The cardiac
      malformation of the fetus may be attributed to the partial duplication of
      chromosome 18p. Combined cytogenetic and molecular methods can facilitate
      prenatal detection of genetic abnormalities.

PMID- 30298505
TI  - [Phenotypic and genotypic analysis of 45 cases with Hemoglobin Q-Thailand].
AB  - OBJECTIVE: To explore hematological and molecular characteristics of Hemoglobin Q
      Thailand in Huizhou area of Guangdong Province. METHODS: A total of 34 977
      samples were screened by capillary and agarose gel electrophoresis. Samples
      suspected with HbQ strips were subjected to blood cell count and DNA sequencing.
      Twenty three common mutations associated with alpha- and beta-thalassemia were
      identified by liquid phase chip and diversion hybridization technique. RESULTS:
      The carrier rate of Hb Q-Thailand in Huizhou area was 0.13%. Pedigree analysis
      indicated that the Hb Q-Thailand allele is linked with a leftward single a-globin
      gene deletion (-alpha4.2). Hematological index (HGB, MCV, MCH, HbA, HbA2, HbQ) of
      45 heterozygous carriers of Hb Q-Thailand were (130.25+/-17.37) g/L, (79.81+/
      4.97) fl, (26.38+/-1.48) pg, (71.37+/-5.07)%, (1.65+/-0.45)%, (26.87+/-4.95)%,
      respectively. A statistical difference was also found in their hematological
      index of HbA and HbA2 compared with 408 heterozygous carriers of -alpha4.2
      mutation (P<0.05). CONCLUSION: Hb Q-Thailand has a high detection rate in Huizhou
      area. The allele is mainly in a heterozygous status and linked with -alpha4.2.
      The Hb Q strip can be detected by hemoglobin electrophoresis. When combined with
      other types of thalassemia, the heterozygotes will show unique hematological
      parameters.

PMID- 30298506
TI  - [Analysis of clinical features of patients with de novo primary acute myeloid
      leukemia and various chromosomal karyotypes].
AB  - OBJECTIVE: To explore clinical features of patients with de novo primary acute
      myeloid leukemia (AML) and various chromosomal karyotypes. METHODS: Clinical data
      of 144 patients was retrospectively reviewed. The patients included 76 males and
      68 females, with a median age of 41.5 years and inter-quartile ranging from 25.25
      to 53.75 years. Based on cytogenetic prognostic stratification criteria, the
      patients were divided into good prognosis (GP group, 55 cases), moderate
      prognosis (MP group, 71 cases) and poor prognosis (PP group, 18 cases). The PP
      group was further divided into complex karyotype (CK group, 15 cases) and non
      complex karyotype (NCK group, 3 cases), or monosomy karyotype (MK group, 9 cases)
      and non-monosomy karyotype (NMK group, 9 cases). All data was analyzed by
      Student's test, Chi-square test or rank sum test based on the type of data.
      RESULTS: Comparing the clinical data between GP, MP and PP group, there were
      statistically significant differences in the components of the FAB classification
      and the mutation of NPM1 and CSF1R genes (chi2=125.444, 15.538 and 7.049,
      P<0.05). Compared with the NCK group, the CK group had significantly fewer
      primitive cells in their bone marrow and fewer platelet in their peripheral blood
      (t=-3.059 and -2.830, P<0.05). Compared with the NMK group, the MK group had
      significantly fewer red blood cells and lower hemoglobin in their peripheral
      blood (t=-3.764 and -3.384, P<0.05). CONCLUSION: For patient with de novo primary
      AML, those with GP chromosome are more likely to be M2b or M3 with recurrent
      genetic abnormalities, the MP ones are more likely to be M1, M2a or M5 of AML-NOS
      based on WHO classification and associate with NPM1 mutations, while the PP ones
      are more likely to be M2a of AML-NOS based on WHO classification and M5 with
      recurrent genetic abnormalities and associate with CSF1R mutations. Compared with
      those with NCK chromosomes, the CK ones have lower proportion of primitive cells
      in their bone marrow and fewer platelets in peripheral blood. Compared with those
      with NMK chromosomes, the MK ones have lower red blood cell count and hemoglobin
      in their peripheral blood.

PMID- 30298507
TI  - [Preliminary analysis of genetics and clinical features of patients with acute
      myeloid leukemia and near-tetraploid/tetraploidy karyotype].
AB  - OBJECTIVE: To explore the genetic and clinical features of patients with acute
      myeloid leukemia (AML) and near-tetraploidy/tetraploidy (NT/T) karyotype.
      METHODS: Cytogenetic findings of 1836 cases of primary AML were retrospectively
      analyzed. Karyotypes of the identified cases were confirmed by fluorescence in
      situ hybridization (FISH). Clinical data including gender, age, morphology,
      immunophenotype, genetics, and prognosis were reviewed. RESULTS: Nine male and
      two female patients with NT/T were identified with a median age of 63 years.
      Microscopically, the patients were characterized by large blasts and irregular
      nuclear contours. All patients expressed CD34, and nine of them expressed HLA-DR.
      Ten patients had complete remission during the first course of treatment. One
      patient showed primary drug resistance. CONCLUSION: NT/T AML primarily occurs in
      elder males and has a characteristic morphology and genetics. The prognosis is
      better than AML patients with complex karyotypes.

PMID- 30298508
TI  - [Association of ZP4 gene polymorphism with primary open-angle glaucoma in an
      ethnic Chinese population from Sichuan province].
AB  - OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNP)
      rs547984, rs540782, rs693421 and rs2499601 of Zona Pellucida Glycoprotein 4 (ZP4)
      gene with primary open-angle glaucoma (POAG) among ethnic Han Chinese from
      Sichuan Province. METHODS: A dye terminator-based SNaPshot method was used to
      genotype 336 patients with POAG and 768 healthy controls. RESULTS: No significant
      difference was detected in allelic frequencies of rs547984, rs540782, rs693421
      and rs2499601 between the two groups (P>0.05). Haplotypic analysis showed a
      significant difference in G-G-A-G haplotype formed by the 4 SNPs between the POAG
      and the control groups (P<0.05). CONCLUSION: ZP4 gene SNPs rs547984, rs540782,
      rs693421, rs2499601 are not associated with POAG among ethnic Hans from Sichuan.

PMID- 30298509
TI  - [Molecular basis of an individual with CisAB subtype of ABO blood group].
AB  - OBJECTIVE: To explore the molecular basis for an individual with CisAB subtype of
      the ABO blood group. METHODS: ABO antigen and serum antibody of the proband were
      detected with a serological method. Exons 5 to 7 of the ABO gene were amplified
      with PCR and sequenced bidirectionally. Allele-specific amplification for exon 6
      to 7 was also carried out. RESULTS: The proband was assigned as a CisAB phenotype
      based on his serological characteristics. Heterozygous variations including
      220C/T, 261G/del, 297A/G, 467C/T, 646A/T, 681A/G, 771C/T, 803G/C, 829A/G and
      1009A/G of the ABO gene were identified through direct sequencing, which was
      assigned as CisAB01var/O02 genotype. Allele-specific amplification indicated that
      the proband carried an O02 allele and a CisAB01var allele. Compared with A102,
      the CisAB01var allele has two nucleotide substitutions at 803G>C and 1009A>G,
      which resulted in replacement of amino acid Gly by Ala at position 268 and Arg by
      Gly at position 337. CONCLUSION: The CisAB subtype was identified with 803G>C and
      1009A>G variants in the alpha1,3-N-acetyl-galactosaminyltransferase gene compared
      with that of the A102 allele.

PMID- 30298510
TI  - [Analysis of a 389 T>C variant of alpha-1,3-N-acetylgalactoseaminotransferase
      gene].
AB  - OBJECTIVE: To study the effect of a 389T>C variant in the alpha-1,3-N
      acetylgalactosaminyltransferase gene on the expression of A antigen by molecular
      genetic analysis of an individual with Ax subtype of ABO variant. METHODS:
      Serological assays were carried out to identify the ABO blood group of the
      proband. Exons 6 and 7 of the ABO gene were amplified with PCR and directly
      sequenced. Following identification of the heterozygote site, specific primers
      were used to determine the haplotype of the ABO gene. RESULTS: Weak A antigen was
      detected on red blood cells from the proband. And anti-A and anti-B antibodies
      were detected in the serum. DNA sequencing has identified heterozygous 261delG
      and 389T/C variants in exons 6 and 7. By haplotype analysis, two alleles Ax22 and
      O01 were found. Compared with that of A101, the Ax22 allele had a nucleotide
      change (T to C) at position 389, which resulted in an amino acid substitution
      (L130P). CONCLUSION: T>C at nt389 of the alpha-1,3-N-acetylgalactosaminyl
      transferase gene can result in significant reduction of A antigen activity.

PMID- 30298511
TI  - [Polymorphisms of MICA gene and their linkage disequilibrium with HLA-B among
      ethnic Han Chinese from Shenzhen].
AB  - OBJECTIVE: To study the distribution of MICA alleles among ethnic Han Chinese
      blood donors from Shenzhen and their linkage disequilibrium with HLA-B gene.
      METHODS: For 143 randomly selected blood donors, the MICA and HLA-B alleles were
      determined with a PCR-sequence based typing (SBT) method. Allelic frequency,
      haplotypic diversity and linkage disequilibrium were analyzed with a Pypop
      software. RESULTS: Thirteen MICA and 35 HLA-B alleles were identified among the
      143 blood donors, among which MICA*008:01 had the highest frequency (76/286),
      whilst MICA*008:01-HLA-B*40:01 and MICA*010-HLA-B*46:01 were the most common
      haplotypes. No novel allele was identified. CONCLUSION: The allele frequencies,
      haplotype diversities and linkage disequilibrium parameters under a high
      resolution can facilitate further studies and applications of the MICA and HLA-B
      genes.

PMID- 30298512
TI  - [Role of NRXN-NLGN-SHANK pathway gene variations in the pathogenesis of autism
      spectrum disorders].
AB  - Autism spectrum disorders (ASDs) comprise a group of common neurodevelopmental
      disorders whose pathogenesis remains unclear. More than 100 genes have been
      associated with ASDs, some of which have shown to play important roles in the
      development and function of synapses, a crucial step of information transmission
      between neurons. Studies have found abnormalities in synaptic transmission,
      density, and structures in the brains of autistic patients. NRXN-NLGN-SHANK
      pathway has been associated with synaptic function of the brain, and its primary
      role is to regulate synaptic formation, elimination, plasticity and maturation.
      Genes including NRXN, NLGN, SHANK, and PSD95 are involved in the NRXN-NLGN-SHANK
      pathway. Mutations of such genes may lead to dysfunction of the pathway and ASDs
      related phenotypes found in patients and animal models. This paper has provided a
      review for the research progress made on the mutations of NRXN-NLGN-SHANK pathway
      related genes and their roles in the pathogenesis of ASDs.

PMID- 30298513
TI  - [Roles of exosomes in Parkinson's disease and amyotrophic lateral sclerosis].
AB  - Exosomes, as a kind of extracellular vesicles generated by inward budding of the
      endosomes to form multi-vesicular bodies (MVBs), are secreted into the
      extracellular milieu and the systemic circulation thereafter. By endocytosis,
      direct fusion or receptor-ligand interactions, exosomes can interact with
      receptor cells and involve in various pathophysiological processes. Accumulating
      evidence have indicated that exosomes may play crucial roles in the pathogenesis
      of many neurodegenerative diseases including Parkinson's disease (PD),
      Huntington's disease (HD), Alzheimer disease (AD) and amyotrophic lateral
      sclerosis (ALS). In this paper, the roles of exosomes in the pathogenesis,
      diagnosis and treatment of PD and ALS are reviewed.

PMID- 30298515
TI  - Label-free quantitative proteomic analysis of human periodontal ligament stem
      cells by high-resolution mass spectrometry.
AB  - BACKGROUND AND OBJECTIVES: Proteome analysis of periodontal ligament stem cells
      (PDLSCs) could be used to study the function of PDL tissue. We used a label-free
      quantitative proteomic technique to investigate differentially expressed proteins
      (DEPs) in human PDLSCs (hPDLSCs) compared to human bone marrow mesenchymal stem
      cells (hBMSCs) and identify proteins specific to hPDLSCs. MATERIAL AND METHODS:
      hPDLSCs (n = 3) and hBMSCs (n = 3) were cultured and harvested for protein
      extraction and trypsin digestion. The proteomes of both cell types were analyzed
      by nano-liquid chromatography/tandem mass spectrometry. DEPs in hPDLSCs compared
      to hBMSCs were detected by label-free quantification and evaluated through signal
      transduction pathway and gene ontology (GO) analysis. RESULTS: In total, 690 and
      771 proteins were identified from hPDLSCs and hBMSCs, of which 561 proteins were
      in common and 124 DEPs were found between hPDLSCs and hBMSCs. Fifty-eight
      proteins were expressed at significantly higher levels in hPDLSCs, whereas 66
      proteins were expressed at lower levels compared to hBMSCs. The more highly
      expressed proteins were associated with translation and initiating protein
      synthesis, and lower expressed proteins were related to cell aging and metabolic
      processes. Proteins unique to hPDLSCs and hBMSCs were associated with translation
      and metabolic processes, respectively. CONCLUSION: Our results demonstrate
      evidence of distinct differences in protein expression between hPDLSCs and hBMSCs
      by using label-free quantitative proteomic analysis which was the first attempt
      in this field. DEPs included previously reported hPDLSC marker proteins and novel
      marker candidates, such as microtubule-associated protein, CTP synthase 1 and
      stathmin, which could be the markers for developing periodontal disease
      diagnostics and therapies.

PMID- 30298514
TI  - Macroscopic features of scurvy in human skeletal remains: A literature synthesis
      and diagnostic guide.
AB  - The past two decades have seen a proliferation in bioarchaeological literature on
      the identification of scurvy, a disease caused by chronic vitamin C deficiency,
      in ancient human remains. This condition is one of the few nutritional
      deficiencies that can result in diagnostic osseous lesions. Scurvy is associated
      with low dietary diversity and its identification in human skeletal remains can
      provide important contextual information on subsistence strategy, resource
      allocation, and human-environmental interactions in past populations. A large and
      robust methodological body of work on the paleopathology of scurvy exists.
      However, the diagnostic criteria for this disease employed by bioarchaeologists
      have not always been uniform. Here we draw from previous research on the skeletal
      manifestations of scurvy in adult and juvenile human skeletal remains and propose
      a weighted diagnostic system for its identification that takes into account the
      pathophysiology of the disease, soft tissue anatomy, and clinical research. Using
      a sample of individuals from the prehistoric Atacama Desert in Northern Chile, we
      also provide a practical example of how diagnostic value might be assigned to
      skeletal lesions of the disease that have not been previously described in the
      literature.

PMID- 30298516
TI  - Positron emission tomography (PET) and magnetic resonance imaging (MRI) for
      assessing tumour resectability in advanced epithelial ovarian/fallopian
      tube/primary peritoneal cancer.
AB  - BACKGROUND: Ovarian cancer is the leading cause of death from gynaecological
      cancer in developed countries. Surgery and chemotherapy are considered its
      mainstay of treatment and the completeness of surgery is a major prognostic
      factor for survival in these women. Currently, computed tomography (CT) is used
      to preoperatively assess tumour resectability. If considered feasible, women will
      be scheduled for primary debulking surgery (i.e. surgical efforts to remove the
      bulk of tumour with the aim of leaving no visible (macroscopic) tumour). If
      primary debulking is not considered feasible (i.e. the tumour load is too
      extensive), women will receive neoadjuvant chemotherapy to reduce tumour load and
      subsequently undergo (interval) surgery. However, CT is imperfect in assessing
      tumour resectability, so additional imaging modalities can be considered to
      optimise treatment selection. OBJECTIVES: To assess the diagnostic accuracy of
      fluorodeoxyglucose-18 (FDG) PET/CT, conventional and diffusion-weighted (DW) MRI
      as replacement or add-on to abdominal CT, for assessing tumour resectability at
      primary debulking surgery in women with stage III to IV epithelial
      ovarian/fallopian tube/primary peritoneal cancer. SEARCH METHODS: We searched
      MEDLINE and Embase (OVID) for potential eligible studies (1946 to 23 February
      2017). Additionally, ClinicalTrials.gov, WHO-ICTRP and the reference list of all
      relevant studies were searched. SELECTION CRITERIA: Diagnostic accuracy studies
      addressing the accuracy of preoperative FDG-PET/CT, conventional or DW-MRI on
      assessing tumour resectability in women with advanced stage (III to IV)
      epithelial ovarian/fallopian tube/primary peritoneal cancer who are scheduled to
      undergo primary debulking surgery. DATA COLLECTION AND ANALYSIS: Two authors
      independently screened titles and abstracts for relevance and inclusion,
      extracted data and performed methodological quality assessment using QUADAS-2.
      The limited number of studies did not permit meta-analyses. MAIN RESULTS: Five
      studies (544 participants) were included in the analysis. All studies performed
      the index test as replacement of abdominal CT. Two studies (366 participants)
      addressed the accuracy of FDG-PET/CT for assessing incomplete debulking with
      residual disease of any size (> 0 cm) with sensitivities of 1.0 (95% CI 0.54 to
      1.0) and 0.66 (95% CI 0.60 to 0.73) and specificities of 1.0 (95% CI 0.80 to 1.0)
      and 0.88 (95% CI 0.80 to 0.93), respectively (low- and moderate-certainty
      evidence). Three studies (178 participants) investigated MRI for different target
      conditions, of which two investigated DW-MRI and one conventional MRI. The first
      study showed that DW-MRI determines incomplete debulking with residual disease of
      any size with a sensitivity of 0.94 (95% CI 0.83 to 0.99) and a specificity of
      0.98 (95% CI 0.88 to 1.00) (low- and moderate-certainty evidence). For abdominal
      CT, the sensitivity for assessing incomplete debulking was 0.66 (95% CI 0.52 to
      0.78) and the specificity 0.77 (95% CI 0.63 to 0.87) (low- and low-certainty
      evidence). The second study reported a sensitivity of DW-MRI of 0.75 (95% CI 0.35
      to 0.97) and a specificity of 0.96 (95% CI 0.80 to 1.00) (very low-certainty
      evidence) for assessing incomplete debulking with residual disease > 1 cm. In the
      last study, the sensitivity for assessing incomplete debulking with residual
      disease of > 2 cm on conventional MRI was 0.91 (95% CI 0.59 to 1.00) and the
      specificity 0.97 (95% CI 0.87 to 1.00) (very low-certainty evidence). Overall,
      the certainty of evidence was very low to moderate (according to GRADE), mainly
      due to small sample sizes and imprecision. AUTHORS' CONCLUSIONS: Studies
      suggested a high specificity and moderate sensitivity for FDG-PET/CT and MRI to
      assess macroscopic incomplete debulking. However, the certainty of the evidence
      was insufficient to advise routine addition of FDG-PET/CT or MRI to clinical
      practice..In a research setting, adding an alternative imaging method could be
      considered for women identified as suitable for primary debulking by abdominal
      CT, in an attempt to filter out false-negatives (i.e. debulking, feasible based
      on abdominal CT, unfeasible at actual surgery).

PMID- 30298517
TI  - Anti-alcohol liver disease effect of Gentianae macrophyllae extract through
      MAPK/JNK/p38 pathway.
AB  - OBJECTIVES: The hepatoprotective effect of Gentianae macrophyllae root extract
      (GME) on alcoholic liver disease (ALD) was evaluated through ethanol induced ALD
      animal model. METHODS: Mice were randomly divided into control normal group (10
      mice), ethanol-induced ALD model group (10 mice) and GME plus ethanol group (30
      mice). Mice in model group were given intragastric administration with 50% (v/v)
      ethanol aqueous solution (200 MUl for each) once daily for 19 days. Mice in
      control normal group received equal volumes of water. Mice in GME plus ethanol
      group were given intragastric administration with 50% (v/v) ethanol aqueous
      solution (200 MUl for each) once daily at 10:00 a.m., after 1 h, mice in GME
      group sequentially were treated with 20, 40 and 100 mg/kg of GME by gastric
      gavage for 19 days. the average food and water consumed by the mice in every
      group were recorded every 2 days and body weight of every mouse in every group
      was measured every 2 days. KEY FINDINGS: Results showed that GME significantly
      improved alcohol induced liver injury in a dose-dependent manner. The impaired
      hepatic tissue structure was repaired and the collagen deposition declined after
      GME administration. Meanwhile, the level of malonaldehyde (MDA), Aspartate
      transaminase (AST) and alanine transaminase (ALT) (indicators of liver damage) in
      blood serum were significantly controlled by GME with a dose-dependent manner,
      moreover, body weight and liver index were also improved after administration of
      GME. Pro-inflammatory cytokines including MCP-1, TNF-alpha, IL-1 and IL-6 were
      detected through RT-PCR and ELISA in experiment and GME can significantly inhibit
      the expression of TNF-alpha, IL-1 and IL-6 but have no effect on MCP-1. In order
      to explore the mechanism of GME on ALD, MAPKs pathway was examined and results
      indicated that GME attenuated ALD through inhibiting the phosphorylation of JNK
      and P38 and further suppressing the initiation of inflammation. CONCLUSIONS: GME
      attenuated ALD through inhibiting the phosphorylation of JNK and P38 and further
      suppressing the initiation of inflammation.

PMID- 30298518
TI  - Implicit motives and basic psychological needs.
AB  - The present article starts with discussing similarities and differences between
      conceptualizations of human needs in self-determination theory (SDT; Deci & Ryan
      [1985], Intrinsic motivation and self-determination in human behavior; Deci &
      Ryan [2000], Nebraska symposium on motivation: Perspectives on motivation) and
      motive disposition theory (MDT; McClelland, Human motivation, 1985). The second
      section focuses on the two-process model of psychological needs (Sheldon [2011],
      Psychological Review, 118: 552), which aims to integrate the two approaches,
      whereas the third section highlights some aspects of both theories that are still
      decoupled or even contradictory, but nevertheless still have a high potential to
      be linked. These three aspects are (a) the noncorresponding concepts of implicit
      power motive (MDT) and basic need for autonomy (SDT); (b) the differentiation of
      needs into hope and fear components, which is theoretically embedded in MDT, but
      not in SDT; and (c) MDT researchers' differentiation into an implicit and
      explicit motivational system, which is not included in SDT. Particularly, the
      last section highlights the potential for areas in which further integration is
      possible, which provides a foundation for comprehensive and exciting research on
      human motivation.

PMID- 30298519
TI  - Development of non-governmental organisation-academic partnership to tackle
      rabies in Africa and Asia.
AB  - Rabies kills approximately 60,000 people each year, mainly in sub-Saharan Africa
      and Asia, of which 40% of victims are less than 15 years old. Once clinical signs
      develop, the disease is almost invariably fatal. Globally, rabies has been
      estimated to cause 3?7 million disability-adjusted life years and $8?6B in
      economic losses annually. The vast majority of human rabies cases are caused by
      bites from rabies infected dogs. Despite this loss of human life and resultant
      economic and societal costs, rabies can be prevented in both humans and dogs by
      vaccination. This has been demonstrated in many countries, notably in Central and
      South America, where large-scale, high coverage mass dog vaccination programmes
      have dramatically reduced the incidence of rabies. Even in parts of Africa and
      Asia, projects have shown that rabies can be eliminated locally. Nevertheless,
      rabies remains an important cause of mortality in many sub-Saharan and Asian
      countries. The reasons why some countries have been able to effectively eliminate
      rabies whereas others have not are complex and often impossible to definitively
      identify; commonly cited explanations include political, economic, logistical and
      societal barriers.

PMID- 30298520
TI  - Diversity of oil yield, fatty acids, tocopherols, tocotrienols, and sterols in
      the seeds of 19 interspecific grapes crosses.
AB  - BACKGROUND: The seeds of Vitis vinifera grapes have been studied extensively but
      knowledge about the interspecific crosses of other Vitis species (e.g. V.
      vinifera, V. amurensis, V. rupestris, V. riparia, and V. labruska) is very
      limited. RESULTS: The oil yields recovered from the grape seeds ranged between 7
      and 160 g kg-1 dw. The main fatty acids were linoleic (72.5-83.1%), oleic (6.2
      15.5%), and palmitic (5.4-13.2%), which together constituted 92.8-97.1% of the
      total detected fatty acids. The total concentration of tocopherol (T) and
      tocotrienol (T3) homologues was between 0.785 and 9.033 g kg-1 oil. The
      concentration of sterols varied significantly and ranged between 2.912 and
      105.962 g kg-1 oil. The beta-sitosterol constituted 68.2-86.3% of the total
      content of sterols. The oil yield in grape seeds significantly correlated with
      the oleic acid, alpha-linolenic acid, alpha-T, alpha-T3, gamma-T3, campesterol,
      Delta5-stigmasterol, beta-sitosterol, and total Ts + T3 s and sterols.
      CONCLUSION: The present study demonstrated that seed oil recovered from different
      interspecific Vitis crosses is a rich source of minor lipophilic bioactive
      compounds, especially genotypes with low oil content. They can be used to enrich
      plant oils that are poor in tocotrienols and/or phytosterols without changing the
      fatty acid composition of main oil, due to low enrichment quantities (micro
      blends). (c) 2018 Society of Chemical Industry.

PMID- 30298521
TI  - Sensory evaluation of low-fat yoghurt produced with microbial transglutaminase
      and comparison with physicochemical evaluation.
AB  - BACKGROUND: Low-fat or non-fat yoghurts are popular nowadays. However, their
      texture is not good and they show considerable syneresis with time. The aim of
      this research was to evaluate the effect of the application of transglutaminase
      (TG) to low-fat yoghurt to determine if similar sensory properties to those of
      full-fat yoghurt can be obtained. Methods of adding TG (prior or simultaneous
      with fermentation), dose, and TG origin were evaluated. Correlations between
      sensory and physicochemical parameters were assessed. RESULTS: The results showed
      no significant differences between TG addition methods in terms of the
      quantitative and qualitative sensory attributes studied. Simultaneous addition of
      TG was preferred to speed up the process. A dose of 1 U g-1 was selected as
      optimal. Few differences were detected due to the origin of the TG. They were not
      significant although some differences were observed in terms of density,
      bitterness, and syneresis compared with low and full-fat yoghurts. CONCLUSION:
      The results showed that sensory parameters cannot be associated with only one
      physicochemical parameter in yoghurt evaluation. Transglutaminase can be used as
      a substitute for stabilizers in the production of low-fat yoghurt, maintaining
      good sensory properties and avoiding initial syneresis. (c) 2018 Society of
      Chemical Industry.

PMID- 30298522
TI  - Different Clinical and Pathologic Determinants Might be Possible to Predict
      Invasive Breast Cancer in Ductal Carcinoma In Situ in Ultrasound-Guided Core
      Needle Biopsy.

PMID- 30298523
TI  - Cryoprotectant-free vitrification of spermatozoa: Fish as a model of human.
AB  - Post-thawing motility of spermatozoon, which is directly correlated with the
      integrity of mitochondrion, is the main parameter for evaluation of respective
      cryopreservation treatments. In this review, we describe our model of
      mitochondrial apparatus of spermatozoa and behaviour of this apparatus during
      cryopreservation. This model shows why a priori the mitochondrial apparatus of
      the human spermatozoon is expected to be more cryo-stable than the mitochondrial
      apparatus of the fish spermatozoon. Negative changes of mitochondrial membrane
      potential are a good indicator of the functional normality of mammalian and fish
      spermatozoa. It is concluded that the cryostability of mitochondrial membranes of
      fish spermatozoa is lower than that of human spermatozoa, and protocols for
      effective cryopreservation of fish spermatozoa can be extrapolated to human
      spermatozoa. It is also provided a biological explanation for why cryoprotectant
      free vitrification for human ejaculates is better than conventional freezing and
      vitrification with cryoprotectants. This review also includes a description of
      the various technologies of vitrification of human and fish spermatozoa. For
      cryobiological investigations, we propose to evaluate the fish spermatozoon as a
      suitable representative model of the human spermatozoon.

PMID- 30298524
TI  - Redesign of the Laplacian kernel for improvements in conductivity imaging using
      MRI.
AB  - PURPOSE: To develop an electrical property tomography reconstruction method that
      achieves improvements over standard method by redesigning the Laplacian kernel.
      THEORY AND METHODS: A decomposition property of the governing PET equation shows
      the possibility of redesigning the Laplacian kernel for conductivity
      reconstruction. Hence, the discrete Laplacian operator used for electrical
      property tomography reconstruction is redesigned to have a Gaussian-like
      envelope, which enables manipulation of the spatial and spectral response. The
      characteristics of the proposed kernel are investigated through numerical
      simulations and in vivo brain experiments. RESULTS: The proposed method reduces
      textured noise, which hampers observing features of the conductivity image.
      Furthermore, the proposed scheme can mitigate the propagation of local phase
      error such as flow-induced phase. By doing so, the proposed method can recover
      feature information in conductivity (or resistivity) images. Lastly, the proposed
      kernel can be extended to other electrical property tomography reconstructions,
      improving the quality of images. CONCLUSION: An alternative design of the
      Laplacian kernel for conductivity imaging has been developed to mitigate the
      textured noise and the propagation of local phase artifact.

PMID- 30298525
TI  - Copula selection models for non-Gaussian outcomes that are missing not at random.
AB  - Missing not at random (MNAR) data pose key challenges for statistical inference
      because the substantive model of interest is typically not identifiable without
      imposing further (eg, distributional) assumptions. Selection models have been
      routinely used for handling MNAR by jointly modeling the outcome and selection
      variables and typically assuming that these follow a bivariate normal
      distribution. Recent studies have advocated parametric selection approaches, for
      example, estimated by multiple imputation and maximum likelihood, that are more
      robust to departures from the normality assumption compared with those assuming
      that nonresponse and outcome are jointly normally distributed. However, the
      proposed methods have been mostly restricted to a specific joint distribution
      (eg, bivariate t-distribution). This paper discusses a flexible copula-based
      selection approach (which accommodates a wide range of non-Gaussian outcome
      distributions and offers great flexibility in the choice of functional form
      specifications for both the outcome and selection equations) and proposes a
      flexible imputation procedure that generates plausible imputed values from the
      copula selection model. A simulation study characterizes the relative performance
      of the copula model compared with the most commonly used selection models for
      estimating average treatment effects with MNAR data. We illustrate the methods in
      the REFLUX study, which evaluates the effect of laparoscopic surgery on long-term
      quality of life in patients with reflux disease. We provide software code for
      implementing the proposed copula framework using the R package GJRM.

PMID- 30298526
TI  - Association between self-reported bruxism and anger and frustration.
AB  - BACKGROUND: Even though bruxism has been shown to be associated with several
      psychological factors, few studies have been performed on its relationships with
      anger and frustration. OBJECTIVE: This study aimed to determine the association
      between self-reported awake and sleep bruxism and anger and frustration. METHODS:
      In this longitudinal observational study, 55 healthy adult participants with
      "possible" bruxism reported their experienced level of bruxism and several
      psychosocial factors and lifestyle factors for 28 consecutive days using a
      personal logbook. The logbook consisted of a daily diary and a weekly
      questionnaire composed of Dutch versions of validated questionnaires. The primary
      outcome data were analysed using multiple regression models. RESULTS: An increase
      in SB of 1 unit (on a scale ranging from 1 to 10) was associated with an increase
      in the anger-scale of 0.03 units, and the frustration-scale of 0.04 units.
      However, the random intercepts were 0.22 for anger and 0.19 for frustration,
      meaning that there were major differences between individuals. For awake bruxism
      (AB), the effects were an increase of 0.04 for anger with a random intercept of
      0.21 and an increase of 0.03 for frustration with a random intercept of 0.06. The
      effects of anger and frustration on both SB and AB were not statistically
      significant. CONCLUSION: The association between anger and frustration and self
      reported bruxism is small on group level. In individual cases, anger and
      frustration and self-reported bruxism may be co-existent.

PMID- 30298527
TI  - From Nose to Gut - The Role of the Microbiome in Neurological Disease.
AB  - Inflammation and neurodegeneration are key features of many chronic neurological
      diseases, yet the causative mechanisms underlying these processes are poorly
      understood. There has been mounting interest in the role of the human microbiome
      in modulating the inflammatory milieu of the central nervous system in health and
      disease. To date, most research has focussed on a gut-brain axis, with other
      mucosal surfaces being relatively neglected. We herein take the novel approach of
      comprehensively reviewing the roles of the microbiome across several key mucosal
      interfaces - the nose, mouth, lung, and gut - in health and in Parkinson's
      disease (PD), Alzheimer's disease (AD) and multiple sclerosis (MS). This review
      systematically appraises the anatomical and microbiological landscape of each
      mucosal surface in health and disease before considering relevant mechanisms that
      may influence the initiation and progression of PD, AD, and MS. The cumulative
      effects of dysbiosis from the nose to the gut may contribute significantly to
      neurological disease through a wide variety of mechanisms, including direct
      translocation of bacteria and their products, and modulation of systemic or
      central nervous system-specific immunity. This remains an understudied and
      exciting area for future research and may lead to the development of therapeutic
      targets for chronic neurological disease. This article is protected by copyright.
      All rights reserved.

PMID- 30298528
TI  - Reticular pseudodrusen: current understanding.
AB  - Reticular pseudodrusen (RPD), also known as subretinal drusenoid deposits,
      represent a morphological change to the retina distinct from other subtypes of
      drusen by being located above the level of the retinal pigment epithelium.
      Although they can infrequently appear in individuals with no other apparent
      pathology, their highest rates of occurrence are in association with age-related
      macular degeneration (AMD), for which they hold clinical significance by being
      highly correlated with end-stage disease sub-types, choroidal neovascularisation
      and geographic atrophy. Reticular pseudodrusen are also found in other diseases,
      most notably Sorsby's fundus dystrophy, pseudoxanthoma elasticum and acquired
      vitelliform lesions. They are found more frequently in females, with increased
      age and more commonly bilaterally than unilaterally. Increased risk of RPD
      formation is conveyed by genetic variants known to increase risk of AMD
      development, including complement factor H, age-related maculopathy
      susceptibility 2, and high-temperature requirement A serine peptidase 1; however,
      to date, no genetic factor has been found to predispose to RPD independent of
      those that carry risks for AMD. They have typical features visible on multimodal
      imaging, identifiable either as single lesions or more commonly in yellowish
      white net-like patterns on colour fundus photography and are particularly
      distinguishable using spectral domain optical coherence tomography, fundus auto
      fluorescence, and near infrared reflectance imaging. On histological examination,
      RPD have been shown to have distinct compositions in comparison to typical
      drusen, suggesting different pathways of pathogenesis. Although their aetiology
      remains unclear, presence of opsin within lesions, a high topographic association
      with areas of highest rod-photoreceptor concentration and functional deficits
      most pronounced within the scotopic range, has implicated rod photoreceptor
      dysfunction as a component of RPD.

PMID- 30298530
TI  - Differential pharmacokinetic interaction of cyclosporine and tacrolimus with
      colchicine in renal allograft recipients.

PMID- 30298529
TI  - The eMERGE genotype set of 83,717 subjects imputed to ~40 million variants genome
      wide and association with the herpes zoster medical record phenotype.
AB  - The Electronic Medical Records and Genomics (eMERGE) network is a network of
      medical centers with electronic medical records linked to existing biorepository
      samples for genomic discovery and genomic medicine research. The network sought
      to unify the genetic results from 78 Illumina and Affymetrix genotype array
      batches from 12 contributing medical centers for joint association analysis of
      83,717 human participants. In this report, we describe the imputation of eMERGE
      results and methods to create the unified imputed merged set of genome-wide
      variant genotype data. We imputed the data using the Michigan Imputation Server,
      which provides a missing single-nucleotide variant genotype imputation service
      using the minimac3 imputation algorithm with the Haplotype Reference Consortium
      genotype reference set. We describe the quality control and filtering steps used
      in the generation of this data set and suggest generalizable quality thresholds
      for imputation and phenotype association studies. To test the merged imputed
      genotype set, we replicated a previously reported chromosome 6 HLA-B herpes
      zoster (shingles) association and discovered a novel zoster-associated loci in an
      epigenetic binding site near the terminus of chromosome 3 (3p29).

PMID- 30298531
TI  - Evaluation of a new matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry system for the identification of yeast isolation.
AB  - BACKGROUND: Currently, three commercial in vitro diagnostic matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems are
      widely used in clinical laboratories. The ASTA MicroIDSys system (ASTA Inc, South
      Korea) is a newly developed MALDI-TOF MS system used for the identification of
      pathogenic microorganisms. In the present study, we assessed the performance of
      the ASTA MALDI-TOF MS system for the identification of pathogenic yeast from
      clinical samples. METHODS: We tested 284 clinical yeast isolates from various
      clinical specimens using ASTA MALDI-TOF MS, and the results were compared with
      those using molecular sequencing of the ITS or D1-D2 regions of rDNA and
      biochemical assays. RESULTS: A total of 284 isolates were tested and found to be
      distributed across 14 species including Candida albicans (n = 100) and other
      yeast species (n = 184). ASTA MALDI-TOF MS correctly identified 95.1% (270/284)
      of the yeast species compared to molecular sequencing. Among them, 262 isolates
      showed acceptable MALDI-TOF MS scores (>=140), and 98.1% (257/262) isolates were
      identified correctly. In addition, among 22 isolates with a MALDI-TOF MS score
      <140, 59.1% (13/22) of the isolates showed concordance with molecular typing at
      the species level. Clustering analysis revealed the effectiveness of the new
      MALDI-TOF MS system for the identification of yeast species. CONCLUSIONS: ASTA
      MALDI-TOF MS showed high accuracy in the identification of yeast species; it
      involves facile sample preparation and extraction procedures. ASTA MALDI-TOF MS
      is expected to be useful for yeast identification in clinical microbiology
      laboratories due to its reliability and cost-effectiveness.

PMID- 30298532
TI  - Maternal and perinatal outcomes after elective induction of labor at 39 weeks in
      uncomplicated singleton pregnancy: a meta-analysis.
AB  - OBJECTIVE: The rate of maternal and perinatal complications increases after 39
      weeks' gestation in both unselected and complicated pregnancies. The aim of this
      study was to synthesize quantitatively the available evidence on the effect of
      elective induction of labor at 39 weeks on the risk of Cesarean section, and on
      maternal and perinatal outcomes. METHODS: PubMed, US Registry of Clinical Trials,
      SCOPUS and CENTRAL databases were searched from inception to August 2018.
      Additionally, the references of retrieved articles were searched. Eligible
      studies were randomized controlled trials of singleton uncomplicated pregnancies
      in which participants were randomized between 39 + 0 and 39 + 6 gestational weeks
      to either induction of labor or expectant management. The risk of bias of
      individual studies was assessed using the Cochrane Risk of Bias Tool. The overall
      quality of evidence was assessed according to the GRADE guideline. Primary
      outcomes included Cesarean section, maternal death and admission to the neonatal
      intensive care unit (NICU). Secondary outcomes included operative delivery, Grade
      3/4 perineal laceration, postpartum hemorrhage, maternal infection, hypertensive
      disease of pregnancy, maternal thrombotic events, length of maternal hospital
      stay, neonatal death, need for neonatal respiratory support, cerebral palsy,
      length of stay in NICU and length of neonatal hospital stay. Pooled risk ratios
      (RRs) were calculated using random-effects models. RESULTS: The meta-analysis
      included five studies (7261 cases). Induction of labor was associated with a
      decreased risk for Cesarean section (moderate quality of evidence; RR 0.86 (95%
      CI, 0.78-0.94); I2  = 0.1%), maternal hypertension (moderate quality of evidence;
      RR 0.65 (95% CI, 0.57-0.75); I2  = 0%) and neonatal respiratory support (moderate
      quality of evidence; RR 0.73 (95% CI, 0.58-0.95); I2  = 0%). Neonates born after
      induction weighed, on average, 81 g (95% CI, 63-100 g) less than those born after
      expectant management. No significant effects were found for the other outcomes
      with the available data. The main limitation of our analysis was that the
      majority of data were derived from a single large study. A second limitation
      arose from the open-label design of the studies, which may theoretically have
      affected the readiness of the attending clinician to resort to Cesarean section.
      CONCLUSIONS: Elective induction of labor in uncomplicated singleton pregnancy at
      39 weeks' gestation is not associated with maternal or perinatal complications
      and may reduce the need for Cesarean section, risk of hypertensive disease of
      pregnancy and need for neonatal respiratory support. Copyright (c) 2018 ISUOG.
      Published by John Wiley & Sons Ltd.

PMID- 30298533
TI  - Effect of zinc oxide sources and dosages on gut microbiota and integrity of
      weaned piglets.
AB  - Zinc oxide (ZnO) supplied at pharmacological dosage in diets of weaned piglets
      improves growth performance. However, it causes environmental contamination and
      induces bacterial antibiotic resistance, yet this practice is debated. The
      effects on gut microbiota and integrity in weaned piglets of conventional ZnO at
      nutritional and pharmacological dosage (110 and 2,400 mg/kg Zn, respectively)
      were compared to an alternative ZnO source at 110 and 220 mg/kg Zn. Each of the
      four treatments was applied to four pens (two piglets/pen; weaning age, 20 days)
      for 15 days, and piglets were sampled on day 15 to determine indices of gut
      integrity. Feeding conventional ZnO at 2,400 mg/kg Zn reduced coliforms and
      Escherichia coli in distal small intestine as compared to conventional ZnO at 110
      mg/kg (-1.7 and -1.4 log10 cfu/g, respectively), whereas the alternative ZnO
      reduced only coliforms, irrespective of dosage (-1.6 to -1.7 log10 cfu/g).
      Transepithelial electrical resistance of distal small intestinal mucosa was
      higher for pigs fed the alternative ZnO source as compared with groups fed 110
      mg/kg Zn of conventional ZnO, in line with a trend for higher gene expression of
      claudin-1 and zona occludens-1. Interestingly, the alternative ZnO source at 110
      and 220 mg/kg Zn increased intestinal alkaline phosphatase gene transcript as
      compared to conventional ZnO at 110 mg/kg Zn, whereas the alternative ZnO source
      at 110 mg/kg Zn exhibited higher Zn concentrations in mucosa (2,520 MUg/g) as
      compared to conventional ZnO at 110 mg/kg Zn (1,211 MUg/g). However, assessing
      alkaline phosphatase activity, no significant effects were found. In conclusion,
      the alternative ZnO reduced digesta Enterobacteriaceae numbers and improved gut
      integrity, albeit similar or better, depending on the dosage, to the effects of
      pharmacological dosage of conventional ZnO.

PMID- 30298534
TI  - Information needs in day-to-day operations management in hospital units: A cross
      sectional national survey.
AB  - AIM: To describe and compare shift leaders' important information needs by
      profession, unit, time of day and type of hospital. BACKGROUND: Professionals
      responsible for care provision in hospital units make ad hoc decisions about
      available resources to meet patient care needs but, currently, much effort is
      needed to obtain the necessary information to support decision making. METHODS:
      This survey was carried out in nine randomly chosen hospitals in Finland. Nurses
      and physicians responsible for day-to-day operations were eligible to participate
      (N = 873). The response rate was 65% (n = 570, including 453 nurses and 111
      physicians). Data were collected in 2015-2016 using the Hospital Shift Leaders'
      Information Needs Questionnaire with 114 information need items. RESULTS: Shift
      leaders reported many real-time information needs. Nurses' important information
      needs concerned patients, personnel, and materials, and physicians' needs focused
      on patient care. Large mean differences existed in the needs between nurses and
      physicians, and imaging units when compared to other units. CONCLUSION: Real-time
      information systems for shift leaders should consider the needs of different
      users to support shared situational awareness and operational intelligence.
      IMPLICATIONS FOR NURSING MANAGEMENT: The important information-need items
      identified here may be used in designing and developing information systems that
      better support shift leaders' work in hospitals.

PMID- 30298535
TI  - In vitro functional characterization of the novel DHH mutations
      p.(Asn337Lysfs*24) and p.(Glu212Lys) associated with gonadal dysgenesis.
AB  - In humans, mutations of Desert Hedgehog gene (DHH) have been described in
      patients with 46,XY gonadal dysgenesis (GD), associated or not with
      polyneuropathy. In this study, we describe two patients diagnosed with GD, both
      harboring novel DHH compound heterozygous mutations p.[Tyr176*];[Asn337Lysfs*24]
      and p.[Tyr176*];[Glu212Lys]. To investigate the functional consequences of
      p.(Asn337Lysfs*24) and p.(Glu212Lys) mutations, located within the C-terminal
      part of DHh on auto-processing, we performed in vitro cleavage assays of these
      proteins in comparison with Drosophila melanogaster Hedgehog (Hh). We found that
      p.(Glu212Lys) mutation retained 50% of its activity and led to a partially
      abolished DHh auto-processing. In contrast, p.(Asn337Lysfs*24) mutation resulted
      in a complete absence of auto-proteolysis. Furthermore, we found a different auto
      processing profile between Drosophila Hh and human DHh, which suggests
      differences in the processing mechanism between the two species. Review of the
      literature shows that proven polyneuropathy and GD is associated with complete
      disruption of DHh-N, whereas disruption of the DHh auto-processing is only
      described with GD. We propose a model that may explain the differences between
      Schwann and Leydig cell development by autocrine versus paracrine DHh signaling.
      To our knowledge, this is the first study investigating the effect of DHH
      mutations on DHh in vitro auto-processing.

PMID- 30298536
TI  - Inbreeding shapes tuberculosis progression in female adult badgers (Meles meles).
AB  - In Focus: Beton, C. H., Delahay, R. J., Smith, F. A. P., Robertson, A., McDonald,
      R. A., Young, A. J., Burke T. A., & Hodgson, D. (2018). Inbreeding intensifies
      sex- and age-dependent disease in a wild mammal. Journal of Animal Ecology, 87,
      1497-1499. https://doi.org/10.1111/1365-2656.12878 Increasing crossbreeding of
      relatives promotes inbreeding which, in turn, can cause a reduction in fitness
      and the emergence of a phenomenon known as inbreeding depression. Benton et al.,
      used the badger (Meles meles)-Mycobacterium bovis model system to study the
      relationship between inbreeding, disease, ageing and sex. A link between
      multilocus homozygosity (general effect) and TB progression (measured as antibody
      response to infection) and between homozygosity at specific loci (local effect)
      and TB progression were established in this study, highlighting the importance of
      host genetic background in determining host disease outcomes, and thus on shaping
      disease dynamics in wild populations. Moreover, the authors demonstrated for the
      first time in a natural population that this positive association might be
      modulated by sex and age. In infected individuals, inbreeding only affects
      disease progression in adult females.

PMID- 30298537
TI  - Fabrication Method for a Mounting Jig and Cast Support for Mounting Complete
      Dentures.
AB  - In complete denture fabrication, the definitive maxillary cast is mounted on an
      articulator using a facebow transfer or mounting jig, and the mandibular cast is
      mounted using an interocclusal record. The technique presented describes an easy
      and inexpensive method for fabrication of a mounting jig and rigid cast supports
      for mounting complete dentures.

PMID- 30298538
TI  - Applying ambiguous loss theory to children of parents with an opioid use
      disorder.
AB  - PROBLEM: Opioid use disorder (OUD) has reached epidemic proportions in the United
      States. Children of parents with OUD are an unrepresented population, who often
      suffer consequences from their parent's substance abuse disorder. Such children
      may incur numerous psychosocial and physical losses. Without intervention, they
      are more likely to be diagnosed with a mental illness and/or substance use
      disorder (SUD). METHODS: This paper examines the experiences of children of
      parents with OUD using Boss's theory of ambiguous loss (AL) as a lens. FINDINGS:
      Children growing up with a parent who has an OUD experience AL through that
      parent's physical absence and psychological presence (e.g., the parent is out
      opioid-seeking or in rehab or jail) and psychological absence but physical
      presence (e.g., the parent is high or in withdrawal, or is preoccupied with
      obtaining opioids). Evidence supports the fact that OUDs affect parenting,
      produce changes in the parent-child relationship, and often impact child
      development. Interventions that are child-focused are lacking. CONCLUSIONS: The
      application of AL theory to this problem can enhance health professionals'
      understanding and need for developmentally specific interventions to care for
      this population. Interventions should focus on diminishing stigma and promoting
      psychosocial wellness and resiliency for children of parents with an OUD.

PMID- 30298539
TI  - Prospective evaluation of the limitations of near-infrared imaging in detecting
      axillary sentinel lymph nodes in primary breast cancer.
AB  - We compared the performance of near-infrared imaging using indocyanine green
      (ICG) with the radioisotope (ISO) method to detect sentinel lymph nodes (SLNs) in
      breast cancer, to analyze predictive factors for negative ICG identification. The
      study included 122 patients who underwent sentinel lymph node biopsy (SLNB) using
      the combined ISO and ICG technique for primary breast cancer. We assessed the
      putative association between pathologic/clinical variables and ICG failure to
      detect SLNs. The ISO identification rate was 96.7% and ICG identification 81.9%.
      Overweight patients or presence of macrometastasis in SLNB were associated with
      the risk of ICG failing to detect SLNs (P = 0.02).

PMID- 30298540
TI  - Prognostic significance of genetic biomarkers in isocitrate dehydrogenase-wild
      type lower-grade glioma: the need to further stratify this tumor entity - a meta
      analysis.
AB  - The clinical outcomes of isocitrate dehydrogenase-wild-type (IDH-wt) lower-grade
      glioma (LGG) have been the subject of debate for some time. In this meta
      analysis, we aimed to assess the prognostic values of several known genetic
      markers (e.g. TERT promoter mutation, H3F3A mutation, CDKN2A loss) in this tumor
      group. Four electronic databases, including PubMed, Scopus, Web of Science and
      Virtual Health Library, were searched for relevant articles. Pooled hazard ratio
      (HR) and corresponding 95% confidence interval (CI) for overall survival were
      calculated using a random-effect model weighted by an inverse variance method. A
      total of 11 studies were finally selected from 2274 articles for meta-analyses.
      Several genetic alterations were demonstrated to have a negative impact on
      prognosis of IDH-wt LGGs, specifically TERT promoter mutation (HR, 1.96; 95% CI,
      1.42-2.70), H3F3A mutation (HR, 3.21; 95% CI, 1.86-5.55) and EGFR amplification
      (HR, 1.67; 95% CI, 1.02-2.74). However, CDKN loss, ATRX mutation and coexisting
      gain of chromosome 7/loss of chromosome 10 showed no clinical significance in
      this glioma entity. Our study results demonstrated that IDH-wt LGGs are
      heterogeneous in clinical outcome and not all tumors have a poor prognosis. The
      presence of TERT promoter mutation, H3F3A mutation and EGFR amplification showed
      negative prognostic impacts in this tumor entity. These genetic events can be
      used to better stratify patient outcomes.

PMID- 30298541
TI  - Progestogen for preventing miscarriage in women with recurrent miscarriage of
      unclear etiology.
AB  - BACKGROUND: Progesterone, a female sex hormone, is known to induce secretory
      changes in the lining of the uterus essential for successful implantation of a
      fertilized egg. It has been suggested that a causative factor in many cases of
      miscarriage may be inadequate secretion of progesterone. Therefore, clinicians
      use progestogens (drugs that interact with the progesterone receptors), beginning
      in the first trimester of pregnancy, in an attempt to prevent spontaneous
      miscarriage. This is an update of a review, last published in 2013. OBJECTIVES:
      To assess the efficacy and safety of progestogens as a preventative therapy
      against recurrent miscarriage. SEARCH METHODS: For this update, we searched
      Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO
      International Clinical Trials Registry Platform (ICTRP) (6 July 2017) and
      reference lists from relevant articles, attempting to contact trial authors where
      necessary, and contacted experts in the field for unpublished works. SELECTION
      CRITERIA: Randomized or quasi-randomized controlled trials comparing progestogens
      with placebo or no treatment given in an effort to prevent miscarriage. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trials for
      inclusion and risk of bias, extracted data and checked them for accuracy. Two
      reviewers assessed the quality of the evidence using the GRADE approach. MAIN
      RESULTS: Thirteen trials (2556 women) met the inclusion criteria. Nine of the
      included trials compared treatment with placebo and the remaining four trials
      compared progestogen administration with no treatment. The trials were a mix of
      multicenter and single-center trials, conducted in Egypt, India, Jordan, UK and
      USA. In six trials women had had three or more consecutive miscarriages and in
      seven trials women had suffered two or more consecutive miscarriages. Routes,
      dosage and duration of progestogen treatment varied across the trials. The
      majority of trials were at low risk of bias for most domains. Eleven trials (2359
      women) contributed data to the analyses.The meta-analysis of all women, suggests
      that there is probably a reduction in the number of miscarriages for women given
      progestogen supplementation compared to placebo/controls (average risk ratio (RR)
      0.69, 95% confidence interval (CI) 0.51 to 0.92, 11 trials, 2359 women, moderate
      quality evidence). A subgroup analysis comparing placebo-controlled versus non
      placebo-controlled trials and different routes of administration showed no
      differences between subgroups for miscarriage. However, there appears to be a
      subgroup difference for miscarriage between women with three or more prior
      miscarriages compared to women with two or more miscarriages, with a more
      pronounced effect in women with three or more prior miscarriages. However, it
      should be noted that there was high heterogeneity in the subgroup of women with
      three or more prior miscarriages.None of the trials reported on any secondary
      maternal outcomes, including severity of morning sickness, thromboembolic events,
      depression, admission to a special care unit, or subsequent fertility.There was
      probably a slight benefit for women receiving progestogen seen in the outcome of
      live birth rate (RR 1.11, 95% CI 1.00 to 1.24, 7 trials, 2086 women, moderate
      quality evidence). While the rate of preterm birth is probably reduced for women
      receiving progestogen, this outcome was mainly driven by one trial and thus
      should be interpreted with great caution (RR 0.59, 95% CI 0.39 to 0.89, 5 trials,
      811 women, moderate-quality evidence). No clear differences were seen for women
      receiving progestogen for the other secondary outcomes of neonatal death or fetal
      genital abnormalities. A possible reduction in stillbirth was seen, but again
      this outcome was driven mainly by one trial and should be interpreted with
      caution (RR 0.38, 95% CI 0.24 to 0.58, 3 trials, 1199 women). There may be little
      or no difference in the rate of low birthweight and trials did not report on the
      secondary child outcomes of teratogenic effects or admission to a special care
      unit. AUTHORS' CONCLUSIONS: For women with unexplained recurrent miscarriages,
      supplementation with progestogen therapy probably reduces the rate of miscarriage
      in subsequent pregnancies.

PMID- 30298542
TI  - A rare case of disseminated Mycobacterium avium complex with colitis in a renal
      transplant recipient.
AB  - Mycobacterium avium complex (MAC) colitis is a rare complication of
      immunosuppression in solid organ transplant (SOT) recipients. Here, we describe a
      case of disseminated MAC infection with colitis following renal transplantation.
      Despite common pathways of immunosuppression, SOT recipients and human
      immunodeficiency virus (HIV)-infected patients differ in their typical
      presentations of MAC infection. Intestinal infections have been more commonly
      reported in HIV-infected patients than in SOT recipients. The explanation for
      this difference may be related to HIV's targeted effects on the CD4+ T-cell
      reservoir in gut-associated lymphoid tissue.

PMID- 30298543
TI  - Selective Cholecystectomy: using an evidence-based prediction model to plan for
      cholecystectomy.
AB  - BACKGROUND: Symptomatic gall stones are treated safely and efficiently with
      laparoscopic cholecystectomy. Conversion to open cholecystectomy may be
      associated with adverse outcomes. Accurate prediction of conversion should
      decrease the incidence of conversion and improve patient care. METHODS: The
      recent literature on conversion at laparoscopic cholecystectomy is reviewed to
      identify robust prediction models that are both internally and externally
      validated. RESULTS: Two prediction models are identified which meet these
      criteria. CONCLUSIONS: The Cairns Prediction Model using nomograms, is an easily
      applied tool predicting conversion, which is presently in use. Routine use of
      this tool should decrease conversion, and improve the process of patient consent.

PMID- 30298544
TI  - Catalytic Enantioselective Aldol Reactions of Unprotected Carboxylic Acids under
      Phosphine Oxide Catalysis.
AB  - The first catalytic enantioselective aldol reaction of various unprotected
      carboxylic acids is described. In the presence of a chiral bis(phosphine oxide)
      as a Lewis base catalyst, carboxylic acids were activated with silicon
      tetrachloride to form the corresponding bis(trichlorosilyl)enediolates in situ,
      which subsequently underwent an aldol reaction with an aldehyde or a ketone to
      produce beta-hydroxycarboxylic acids in high enantioselectivities of up to 92 %
      ee.

PMID- 30298545
TI  - Bioresorbable polymer-coated thin strut sirolimus-eluting stent vs durable
      polymer-coated everolimus-eluting stent in daily clinical practice: Propensity
      matched one-year results from interventional cardiology network registry.
AB  - OBJECTIVES: We sought to determine the 1-year clinical follow-up in patients
      treated with the thin strut (71 MUm) bioabsorbable polymer-coated sirolimus
      eluting stent (BP-SES) vs durable coating everolimus eluting stent (DP-EES) in
      daily clinical routine. BACKGROUND: Presence of durable polymers may be
      associated with late/very late stent thrombosis occurrence and the need for
      prolonged dual antiplatelet therapy. Bioabsorbable polymers may facilitate stent
      healing, thus enhancing clinical safety. METHODS: Interventional Cardiology
      Network Registry is a prospective, multicenter, observational registry of 21,400
      consecutive patients treated with PCI since 2010. We analyzed 4,670 patients
      treated with either a BP-SES (ALEX, Balton, Poland) or DP-EES (XIENCE, Abbott,
      USA) with available 1-year clinical follow-up using propensity-score matching.
      Outcomes included target vessel revascularization (TVR) as efficacy outcome and
      all cause death, myocardial infarction (MI), and definite/probable stent
      thrombosis as safety outcomes. RESULTS: After propensity score matching, 1,649
      patients treated with BP-SES and 1,649 patients treated with DP-EES were
      selected. Procedural and clinical characteristics were similar between both
      groups. There was no significant difference between tested groups in in-hospital
      mortality. One-year follow-up demonstrated comparable efficacy outcome, TVR (BP
      SES 5.9% vs DP-EES 4.6% P = 0.45), as well as comparable safety outcomes, all
      cause death, MI and definite/probable stent thrombosis. CONCLUSIONS: In this
      multicenter registry, the BP-SES thin strut biodegradable polymer-coated
      sirolimus-eluting stent demonstrated comparable clinical outcomes at 1-year after
      implantation to the DP-EES. These data support the relative safety and efficacy
      of DP-SES in a broad range of patients undergoing percutaneous coronary
      intervention.

PMID- 30298546
TI  - Fat or thin, exercise wins: endurance exercise training reduces inflammatory
      circulating progenitor cells in lean and obese adults.

PMID- 30298547
TI  - Background field removal for susceptibility mapping of human brain with large
      susceptibility variations.
AB  - PURPOSE: In quantitative susceptibility mapping (QSM) of human brain, the
      background field induced by air-tissue interface varies significantly with
      respect to the rotation angle between the head and the static field, which may
      result in substantial error in the estimated magnetic susceptibility values. The
      goal of this study was to develop a strategy to better remove such orientation
      dependent background field. METHODS: An improved background field removal method
      is proposed based on the sophisticated harmonic artifact reduction for phase data
      using a region adaptive kernel (R-SHARP), named iRSHARP. It uses a spatially
      weighted spherical Gaussian kernel exploiting the amplitude, gradient, and wrap
      count of the phase map. The method was validated using both numerical simulations
      and in vivo human brain data at multiple head orientations. Performance was
      compared with the variable kernel (V-SHARP) and R-SHARP methods. RESULTS: The
      proposed iRSHARP method showed improved background removal over R-SHARP while
      cutting the computational time in half. As compared to V-SHARP and R-SHARP, the
      iRSHARP generated local field and susceptibility maps showed fewer artifacts in
      regions of large susceptibility variations, and for the in vivo human brain, the
      susceptibilities of the deep gray matter nuclei were consistent with the in vivo
      gold-standard "Calculation of Susceptibility through Multiple Orientation
      Sampling" (COSMOS) values. CONCLUSION: iRSHARP can remove the orientation
      dependent background field effectively. Using iRSHARP, the paranasal sinus
      regions can be preserved in the brain mask and the brain integrity was conserved,
      which may facilitate further data analysis and clinical application.

PMID- 30298549
TI  - Improved facial affect recognition in patients with first-episode psychosis.
AB  - AIM: The present study aimed at assessing whether impaired facial affect
      recognition (FAR) in patients with first-episode psychosis (FEP) would improve
      after a brief intervention targeting FAR specifically. METHODS: Thirty-five
      outpatients and 38 healthy controls were administered an intervention which
      involved training to recognize emotional information, conveyed by changes in
      facial features. Using a pre- and post-intervention design, two measurements of
      FAR were conducted using an experimental procedure with alternative sets of
      stimuli. RESULTS: We found improved overall FAR performance in both participant
      groups with marked effects in recognizing anger, disgust and fear. Patients' post
      intervention performance was comparable to healthy participants' baseline
      performance. CONCLUSIONS: The present improvement in facial affects recognition
      in FEP patients, despite only somewhat impaired, emphasizes the importance of
      early targeted interventions for FAR in psychosis. Further research is needed to
      assess whether this improvement will generalize to global social functioning.

PMID- 30298548
TI  - Antibiofilm activity substances derived from coral symbiotic bacterial extract
      inhibit biofouling by the model strain Pseudomonas aeruginosa PAO1.
AB  - The mitigation of biofouling has received significant research attention, with
      particular focus on non-toxic and sustainable strategies. Here, we investigated
      quorum sensing inhibitor (QSI) bacteria as a means of controlling biofouling in a
      laboratory-scale system. Approximately, 200 strains were isolated from coral
      (Pocillopora damicornis) and screened for their ability to inhibit quorum sensing
      (QS). Approximately, 15% of the isolates exhibited QSI activity, and a typical
      coral symbiotic bacterium, H12-Vibrio alginolyticus, was selected in order for us
      to investigate quorum sensing inhibitory activity further. Confocal microscopy
      revealed that V. alginolyticus extract inhibited biofilm formation from
      Pseudomonas aeruginosa PAO1. In addition, the secondary metabolites of V.
      alginolyticus inhibited PAO1 virulence phenotypes by downregulating motility
      ability, elastase activity and rhamnolipid production. NMR and MS spectrometry
      suggested that the potential bioactive compound involved was rhodamine
      isothiocyanate. Quantitative real-time PCR indicated that the bacterial extract
      induced a significant downregulation of QS regulatory genes (lasB, lasI, lasR,
      rhlI, rhlR) and virulence-related genes (pqsA, pqsR). The possible mechanism
      underlying the action of rhodamine isothiocyanate analogue involves the
      disruption of the las and/or rhl system of PAO1. Our results highlight coral
      microbes as a bioresource pool for developing QS inhibitors and identifying novel
      antifouling agents.

PMID- 30298550
TI  - CRDSAT Generated by pCARGHO: A New Efficient Lectin-Based Affinity Tag Method for
      Safe, Simple, and Low-Cost Protein Purification.
AB  - Purification of recombinant proteins remains a bottleneck for downstream
      processing. The authors engineered a new galectin 3 truncated form (CRDSAT ),
      functionally and structurally characterized, with preserved solubility and
      lectinic activity. Taking advantage of these properties, the authors designed an
      expression vector (pCARGHO), suitable for CRDSAT -tagged protein expression in
      prokaryotes. CRDSAT binds to lactose-Sepharose with a high specificity and
      facilitates solubilization of fusion proteins. This tag is structurally stable
      and can be easily removed from fusion proteins using TEV protease. Furthermore,
      due to their basic isoelectric point (pI), CRDSAT , and TEV are efficiently
      eliminated using cationic exchange chromatography. When pI of the protein of
      interest (POI) and CRDSAT are close, other chromatographic methods are
      successfully tested. Using CRDSAT tag, the authors purified several proteins from
      prokaryote and eukaryote origin and demonstrated as examples, the preservation of
      both Escherichia coli Thioredoxin 1 and human CDC25Bcd activities. Overall,
      yields of proteins obtained after tag removal are about 5-50 mg per litre of
      bacterial culture. Our purification method displays various advantages described
      herein that may greatly interest academic laboratories, biotechnology, and
      pharmaceutical companies.

PMID- 30298551
TI  - Power and sample size requirements for GEE analyses of cluster randomized
      crossover trials.
AB  - The cluster randomized crossover design has been proposed to improve efficiency
      over the traditional parallel cluster randomized design, which often involves a
      limited number of clusters. In recent years, the cluster randomized crossover
      design has been increasingly used to evaluate the effectiveness of health care
      policy or programs, and the interest often lies in quantifying the population
      averaged intervention effect. In this paper, we consider the two-treatment two
      period crossover design, and develop sample size procedures for continuous and
      binary outcomes corresponding to a population-averaged model estimated by
      generalized estimating equations, accounting for both within-period and
      interperiod correlations. In particular, we show that the required sample size
      depends on the correlation parameters through an eigenvalue of the within-cluster
      correlation matrix for continuous outcomes and through two distinct eigenvalues
      of the correlation matrix for binary outcomes. We demonstrate that the empirical
      power corresponds well with the predicted power by the proposed formulae for as
      few as eight clusters, when outcomes are analyzed using the matrix-adjusted
      estimating equations for the correlation parameters concurrently with a suitable
      bias-corrected sandwich variance estimator.

PMID- 30298553
TI  - Efficiently activated epsilon-poly-L-lysine production by multiple antibiotic
      resistance mutations and acidic pH shock optimization in Streptomyces albulus.
AB  - epsilon-Poly-L-lysine (epsilon-PL) is a food additive produced by Streptomyces
      and is widely used in many countries. Working with Streptomyces albulus FEEL-1,
      we established a method to activate epsilon-PL synthesis by successive
      introduction of multiple antibiotic-resistance mutations. Sextuple mutant R6 was
      finally developed by screening for resistance to six antibiotics and produced
      4.41 g/L of epsilon-PL in a shake flask, which is 2.75-fold higher than the level
      produced by the parent strain. In a previous study, we constructed a double
      resistance mutant, SG-31, with high epsilon-PL production of 3.83 g/L and 59.50
      g/L in a shake flask and 5-L bioreactor, respectively. However, we found that R6
      did not show obvious advantages in fed-batch fermentation when compared with SG
      31. For further activation of epsilon-PL synthesis ability, we optimized the
      fermentation process by using an effective acidic pH shock strategy, by which R6
      synthetized 70.3 g/L of epsilon-PL, 2.79-fold and 1.18-fold greater than that
      synthetized by FEEL-1 and SG-31, respectively. To the best of our knowledge, this
      is the highest reported epsilon-PL production to date. This epsilon-PL
      overproduction may be due to the result of R99P and Q856H mutations in ribosomal
      protein S12 and RNA polymerase, respectively, which may be responsible for the
      increased transcription of the epsilon-poly-lysine synthetase gene (pls) and key
      enzyme activities in the Lys synthesis metabolic pathway. Consequently, epsilon
      PL synthetase activity, intracellular ATP, and Lys concentrations were improved
      and directly contributed to epsilon-PL overproduction. This study combined
      ribosome engineering, high-throughput screening, and targeted strategy
      optimization to accelerate epsilon-PL production and probe the fermentation
      characteristics of hyperyield mutants. The information presented here may be
      useful for other natural products produced by Streptomyces.

PMID- 30298552
TI  - Efficacy of fluid loading as a countermeasure to the hemodynamic and hormonal
      changes of 28-h head-down bed rest.
AB  - After exposure to microgravity, or head-down bed rest (HDBR), fluid loading is
      often used with the intent of increasing plasma volume and maintaining mean
      arterial pressure during orthostatic stress. Nine men (aged 18-32 years)
      underwent three randomized trials with lower body negative pressure (LBNP) before
      and after: (1) 4-h of sitting with fluid loading (1 g sodium chloride/125 mL of
      water starting 2.5-h before LBNP), (2) 28-h of 6-degree HDBR without fluid
      loading, and (3) 28-h of 6-degree HDBR with fluid loading. LBNP was progressive
      from 0 to -40 mmHg. After 28-h HDBR, fluid loading did not protect against the
      loss of plasma volume (-280 +/- 64 mL without fluid loading, -207 +/- 86 with
      fluid loading, P = 0.472) nor did it protect against a drop of mean arterial
      pressure (P = 0.017) during LBNP (Post-28 h HDBR response from 0 to -40 mmHg
      LBNP: 88 +/- 4 to 85 +/- 4 mmHg without fluid loading and 93 +/- 4 to 88 +/- 5
      mmHg with fluid loading, P = 0.557 between trials). However, fluid loading did
      protect against the loss of stroke volume index and central venous pressure
      observed after 28-h HDBR. Fluid loading also attenuated the increase of
      angiotensin II seen after 28-h HDBR and throughout the LBNP protocol (Post-28 h
      HDBR response from 0 to -40 mmHg LBNP: 16.6 +/- 3.4 to 23.7 +/- 5.0 pg/mL without
      fluid loading and 6.1 +/- 0.8 to 12.2 +/- 2.3 pg/mL with fluid loading, P < 0.001
      between trials). Our results indicate that fluid loading did not protect against
      plasma volume loss due to HDBR or change blood pressure responses to LBNP.
      However, changes in central venous pressure, stroke volume and fluid regulatory
      hormones could potentially influence longer duration studies and those with more
      severe orthostatic stress.

PMID- 30298554
TI  - Annotating transcriptional effects of genetic variants in disease relevant
      tissue: Transcriptome-wide allelic imbalance in osteoarthritic cartilage.
AB  - OBJECTIVES: Multiple osteoarthritis (OA) susceptibility single nucleotide
      polymorphisms (SNPs) mark imbalanced expression of positional genes in articular
      cartilage, reflected by unequally expressed alleles among heterozygotes (allelic
      imbalance, AI). Here, we explored the articular cartilage transcriptome from OA
      patients for AI events to identify putative disease driving genetic variation.
      METHODS: AI was assessed in N=42 preserved and N=5 lesioned OA cartilage samples
      (RAAK-study) for which RNA sequencing data was available. Hereto, the count
      fraction of the alternative allele among the alternative and reference allele
      together (phi) was determined for heterozygous individuals. A meta-analysis per
      SNP was performed to generate a meta-phi and P-value per SNP with a multiple
      testing correcting false discovery rate (FDR). To further validate AI events, we
      explored them as function of multiple additional OA features. RESULTS: In total
      2070 SNPs were observed that consistently marked AI of 1031 unique genes in
      articular cartilage. Of these 49 genes were found significantly differentially
      expressed (0.5>FC>2, FDR<0.05) between preserved and paired lesioned cartilage
      and 21 genes previously reported to confer susceptibility for OA and/or related
      phenotypes. Moreover, notable highly significant AI SNPs in the CRLF1, WWP2, and
      RPS3 genes were identified that were related to multiple OA features. CONCLUSION:
      A framework and resulting datasets for researchers in the OA research field to
      probe for disease relevant genetic variation that affects respective gene
      expression in the disease's pivotal affected tissue and likely including putative
      novel compelling OA risk genes such as CRLF1, WWP2, and RPS3. This article is
      protected by copyright. All rights reserved.

PMID- 30298556
TI  - Is dietary melatonin supplementation a viable adjunctive therapy for chronic
      periodontitis?-A randomized controlled clinical trial.
AB  - BACKGROUND AND OBJECTIVE: Melatonin is synthesized naturally by pineal gland and
      responsible for regulation of sleep/waking cycle. It showed appreciated anti
      inflammatory and antioxidant properties. The aim of this randomized clinical
      trial (RCT) was to assess the additive effect of melatonin supplementation in
      insomniac individuals with generalized chronic periodontitis (gCP) after scaling
      and root planing (SRP). MATERIAL AND METHODS: Seventy-four gCP patients with
      primary insomnia participated in this 6-month RCT and randomized into two groups.
      Melatonin group included 38 patients who were subjected to SRP with a 2-month
      regimen of 10 mg oral melatonin capsule once daily before bedtime. In the control
      group, SRP was performed for 36 participants provided with matching placebo
      capsules. The primary treatment outcome was the measurement of clinical
      attachment level gain (CAL gain) after 3 and 6 months of therapy, whereas the
      measurements of pocket depth reduction (PD reduction), bleeding on probing (BOP
      %), and the changes in salivary TNF-alpha levels and Athens insomnia scale (AIS)
      scores represented the secondary endpoints. RESULTS: Melatonin group showed
      significantly greater CAL gain and PD reduction measurements compared to the
      control group at 3 and 6 months of therapy, P < 0.01. Likewise, salivary TNF
      alpha levels and AIS scores were significantly lower in the melatonin group
      compared to placebo group. BOP% improved significantly in both groups without any
      difference. However, salivary TNF-alpha levels exhibited no correlation with
      other clinical variables in both melatonin and placebo groups. CONCLUSION: Daily
      dietary 10 mg of melatonin supplementation might serve as a viable adjunct to SRP
      that yielded significantly greater CAL gain and PD reduction and lower salivary
      TNF-alpha levels and AIS scores in gCP patients with primary insomnia.

PMID- 30298555
TI  - Epidermal barrier function in healthy black South African infants compared with
      adults.
AB  - A cross-sectional observational study of 43 infants and 60 adult women was
      performed in South Africa to assess skin barrier (SB) function through
      noninvasive quantification of transepidermal water loss (TEWL) and skin surface
      hydration (SSH). TEWL and SSH improved with age and in anatomic locations with
      chronic environmental exposure in keeping with reported trends in other
      ethnicities.

PMID- 30298557
TI  - Offspring diet supersedes the transgenerational effects of parental diet in a
      specialist herbivore Neolema abbreviata under manipulated foliar nitrogen
      variability.
AB  - Diet quality influences organismal fitness within and across generations. For
      herbivorous insects, the transgenerational effects of diet remain relatively
      underexplored. Using a 3 * 3 * 2 factorial experiment, we evaluated how N
      enrichment in parental diets of Neolema abbreviata (Larcordaire) (Coleoptera:
      Chrysomelidae), a biological control agent for Tradescantia fluminensis Vell.
      (Commelinaceae), may influence life history and performance of F1 and F2
      offspring under reciprocal experiments. We found limited transgenerational
      effects of foliar nitrogen variability among life-history traits in both larvae
      and adults. Larval weight gain and mortality were responsive to parental diet
      contrary to feeding damage, pupal weight and duration taken to pupate. There were
      significant parental diet * test interactions in larval feeding damage, weight
      gain, pupal weight and time to pupation. Generally, offspring from parents under
      high N plants performed better even under low N test plants. Adult traits
      including oviposition selection, feeding weight and longevity did not respond to
      the effects of parental diet nor its interaction with test diet as was the case
      in the larval stage. However, the main effects of test diet were more important
      in determining adult performance in both generations suggesting limited
      sensitivity to parental diet in the adult stage. Our results show conflicting
      responses to parental diet between larvae and adults of the same generation among
      an insect species with both actively feeding larval and adult life stages. These
      transgenerational effects, or lack thereof, may have implications on the field
      performance of N. abbrevita under heterogeneous nutritional landscapes.

PMID- 30298558
TI  - Evaluation of Flexural Strength of Different Denture Base Materials Reinforced
      with Different Nanoparticles.
AB  - PURPOSE: To evaluate the effect of adding Al2 O3 , SiO2 , and TiO2 nanoparticles
      in ratios of 1, 3, and 5 wt% to different acrylic resins on flexural strength.
      MATERIALS AND METHODS: A total of 210 specimens were prepared in 30 groups (n =
      7/group) (Control, 1% Al2 O3 , 3% Al2 O3 , 5% Al2 O3 , 1% SiO2 , 3% SiO2 , 5%
      SiO2 , 1% TiO2 , 3% TiO2 , 5% TiO2 ). The specimens were polished with 200-, 400
      , and 600-grit abrasive paper to provide a standard surface before testing and
      then suspended in distilled water for 30 days. Flexural strength was measured via
      three-point bending tests. Subsequently, SEM analysis was performed for one
      specimen from each group. Homogeneity of data was assessed by Kolmogov-Smirnov
      test followed by two-way ANOVA and Tukey HSD tests (alpha = 0.05). RESULTS: There
      was a significant increase in the flexural strength of polymethylmethacrylate
      (PMMA) after addition of 1% nanoparticles in both heat-polymerized and
      autopolymerized acrylic resins (p ? 0.05). The flexural strength values of the
      groups to which Al2 O3 and TiO2 nanoparticles were added exceeded those of the
      group with SiO2 addition (p ? 0.05). The electron microscopy images revealed that
      the nanoparticles were more homogeneously dispersed in PMMA with higher flexural
      strength. CONCLUSIONS: The mechanical properties of PMMA can be improved by the
      addition of nanoparticles to PMMA; however, the flexural strength values of PMMA
      decrease with the addition of nanoparticles at higher percentages (3-5%). Hence,
      the ideal filler ratio corresponds to 1%.

PMID- 30298559
TI  - Concept and practice of transradial 5 French percutaneous treatment of coronary
      bifurcation lesions.
AB  - OBJECTIVES: To assess the efficacy and safety of transradial 5 French
      percutaneous treatment of coronary bifurcations using conventional devices.
      BACKGROUND: Radial artery is smaller than femoral artery, and its size may
      potentially limit transradial intervention, especially when coronary anatomy is
      not known. METHODS: Patients with bifurcations lesions undergoing transradial 5
      French ad hoc revascularization were treated according to provisional side branch
      (SB) stenting followed by the POT-SB dilation-final POT sequence. Only
      conventional devices were used. RESULTS: Overall, 80 patients (58 men, 65 +/- 10
      years) were enrolled. True bifurcations accounted for 64% of cases, with the left
      anterior descending artery/diagonal branch being the most frequent bifurcation
      site (n = 37, 46%) and left main coronary artery bifurcation being treated in 6
      (8%) patients. Angiographic success was achieved in 78 (97.5%) patients through a
      5 French guiding catheter whereas in two cases, a 5-6 French guiding catheter
      upgrade was required to optimize SB treatment after the main bifurcation vessel
      have been secured. Overall, procedural success was achieved in all but one
      patient who had periprocedural necrosis following multivessel PCI. Another
      patient underwent target bifurcation revascularization because of a critical
      restenosis in a significant SB yielding an acute coronary syndrome five months
      after the index procedure. CONCLUSIONS: This study demonstrates the feasibility
      of transradial 5 French bifurcation intervention with nondedicated devices and
      preliminary supports its efficacy and safety over a wide range of bifurcation
      anatomy and complexity.

PMID- 30298560
TI  - Efficacy of ketoprofen lysine salt and paracetamol/acetaminophen to reduce pain
      during rapid maxillary expansion: A randomized controlled clinical trial.
AB  - BACKGROUND: Rapid maxillary expansion (RME) is an orthopaedic procedure indicated
      for a wide variety of clinical conditions. AIM: The aim of the study was to
      compare the effects of ketoprofen lysine salt (KLS) vs paracetamol/acetaminophen
      (P) on pain perception during RME. DESIGN: One hundred and fifty-one subjects
      (mean age 8.6 year) were enrolled in this prospective controlled clinical trial
      according to inclusion criteria: prepuberal stage of development, negative
      posterior transverse interarch discrepancy, non-concurrent use of other drugs.
      First phase: n.40 allocated to Group 1 used 40 mg of KLS, n.40 to Group 2 used
      250 mg of P, n.36 to Group 3 as control group. Second phase: n.35 allocated to
      Group 4 used 40 mg ketoprofen lysine salt once a day for the first 3 days of
      activation. Pain experience was reported on a numeric rating scale (0-4) and a
      100-mm visual analogue scale. Pain perception was tested with the Mann-Whitney
      test (P < 0.05). RESULTS: Pain perception was higher during the first 3 days of
      activation and it was described as mild to moderate. Group 1 experienced
      significantly less pain during the fourth, fifth, and sixth day (P < 0.05)
      compared with Group 2. Patients of the Group 4 reported significantly lower pain
      during the whole period of RME activation (P < 0.05). CONCLUSIONS: The perceived
      higher pain was reported during the second and third day of expansion. The
      analgesic effect of KLS is more effective than P during the fourth, fifth, and
      sixth day. The use of KLS during the first 3 days of activation seems to be able
      reducing pain during the whole active phase.

PMID- 30298561
TI  - Genetic diversity and antimicrobial resistance in Staphylococcus aureus and
      coagulase-negative Staphylococcus isolates from bovine mastitis in Minas Gerais,
      Brazil.
AB  - The aims of this study were to determine the antimicrobial susceptibility profile
      and genetic diversity of Staphylococcus spp. isolated from dairy cows in Minas
      Gerais, Brazil, and to assess the relationship among the isolates' susceptibility
      profiles and pulsed-field gel electrophoresis (PFGE) genotypes. Seventy-nine
      isolates were used, including S. aureus (n = 71) and coagulase-negative
      staphylococci (CoNS) (n = 8). Susceptibility to 12 antimicrobial agents was
      performed. All Staphylococcus spp. were subjected to PFGE. Staphylococcus aureus
      and CoNS isolates exhibited full susceptibility only to cephalothin. The greatest
      percentages of resistance among Staphylococcus spp. were observed to penicillins,
      folate pathway inhibitors, and tetracyclines. Twelve S. aureus and four CoNS were
      classified as multidrug resistance strains. Percentage of MRSA was also higher
      among CoNS (75%), compared to S. aureus isolates (2.81%). Adopting 100% of
      similarity, 34 different genotypes were identified. Association of minimum
      spanning tree (MST) analysis with data from municipalities, herds, methicillin
      resistant S. aureus (MRSA), and resistance patterns for all isolates did not show
      any clustering. However, a clustering pattern of bacterial species was observed.
      Results from this study indicate a high frequency of antimicrobial resistance,
      especially among CoNS, and a high genetic diversity among Staphylococcus spp.
      isolated from dairy cows with mastitis in Minas Gerais, Brazil.

PMID- 30298563
TI  - Abstracts for the 44th Annual Meeting of the International Society for Pediatric
      and Adolescent Diabetes (ISPAD), 11-14 October 2018, Hyderabad, India.

PMID- 30298562
TI  - Increased risk of recurrence in resected EGFR-positive pN0M0 invasive lung
      adenocarcinoma.
AB  - BACKGROUND: This study was conducted to evaluate the prognostic and recurrent
      impact of EGFR mutation status in resected pN0M0 lung adenocarcinoma with
      consideration of the histological subtype. METHODS: Following retrospective
      analysis of whole 474 consecutive pathological N0M0 lung adenocarcinoma patients,
      the prognostic significance of EGFR mutation status was evaluated in limited 394
      subjects. Overall survival and recurrence-free interval (RFI) were estimated
      using the Kaplan-Meier method and compared using a log-rank test. Univariate and
      multivariate analyses were performed using Cox proportional hazard models.
      RESULTS: The five-year RFI was 85.7% and 93.3% for EGFR positive (n = 176) and
      negative (n = 218) cases, respectively (hazard ratio [HR] 1.992, 95% confidence
      interval [CI] 1.005-3.982; P = 0.048). Following the exclusion of specific
      subtypes free from recurrence or EGFR mutation (adenocarcinoma in situ, minimally
      invasive adenocarcinoma, and invasive mucinous adenocarcinoma), the five-year RFI
      was obviously poorer in EGFR positive compared to negative cases (80.7% and
      92.1%, respectively; HR 2.163, 95% CI 1.055-4.341; P = 0.035). Multivariate
      analysis excluding the specific subtypes confirmed that male sex, age, current or
      Ex-smoking status, pleural invasion, and EGFR-positive status were independently
      associated with shorter RFI. No significant differences in five-year overall
      survival were found between the EGFR mutation positive and negative groups (88.7%
      and 93.7%, respectively; HR 1.630, 95% CI 0.787-3.432; P = 0.2). CONCLUSION: EGFR
      mutations are associated with recurrence in pN0M0 lung adenocarcinoma. EGFR
      mutation status and histological subtype should be considered when evaluating the
      risk of recurrence in resected lung adenocarcinoma patients.

PMID- 30298564
TI  - Multi-SKAT: General framework to test for rare-variant association with multiple
      phenotypes.
AB  - In genetic association analysis, a joint test of multiple distinct phenotypes can
      increase power to identify sets of trait-associated variants within genes or
      regions of interest. Existing multiphenotype tests for rare variants make
      specific assumptions about the patterns of association with underlying causal
      variants, and the violation of these assumptions can reduce power to detect
      association. Here, we develop a general framework for testing pleiotropic effects
      of rare variants on multiple continuous phenotypes using multivariate kernel
      regression (Multi-SKAT). Multi-SKAT models affect sizes of variants on the
      phenotypes through a kernel matrix and perform a variance component test of
      association. We show that many existing tests are equivalent to specific choices
      of kernel matrices with the Multi-SKAT framework. To increase power of detecting
      association across tests with different kernel matrices, we developed a fast and
      accurate approximation of the significance of the minimum observed P value across
      tests. To account for related individuals, our framework uses random effects for
      the kinship matrix. Using simulated data and amino acid and exome-array data from
      the METabolic Syndrome In Men (METSIM) study, we show that Multi-SKAT can improve
      power over single-phenotype SKAT-O test and existing multiple-phenotype tests,
      while maintaining Type I error rate.

PMID- 30298565
TI  - Effects of galanin receptor 2 and receptor 3 knockout in mouse models of acute
      seizures.
AB  - There exists solid evidence that endogenous galanin and galanin agonists exert
      anticonvulsive actions mediated both by galanin 1 receptor (GAL1-R) and galanin 2
      receptor (GAL2-R). We have now investigated whether depletion of the recently
      identified third galanin receptor, GAL3-R, and that of GAL2-R, alters the
      threshold to the systemically applied gamma-aminobutyric acid (GABA) antagonist
      pentylenetetrazole (PTZ) or to intrahippocampally administered kainic acid (KA).
      In neither model, GAL3-KO mice differed in their latency to the first seizure,
      mean seizure duration, total number of seizures, or time spent in seizures
      compared to wild-type controls. In addition, consistent with previous data, the
      response to PTZ was not altered in GAL2-KO mice. In contrast, intrahippocampal KA
      resulted in a significantly increased number of seizures and time spent in
      seizures in GAL2-KO mice, although the latency to the first seizure and the
      duration of individual seizures was not altered. These results are consistent
      with the previous data showing that GAL2-R knockdown does not affect the number
      of perforant path stimulations required for initiating status epilepticus but
      significantly increases the seizure severity during the ongoing status. In
      conclusion, our data support a specific role of GAL2-R but not of GAL3-R in
      mediating the anticonvulsive actions of endogenous galanin.

PMID- 30298566
TI  - The Impact of Medicaid Enrollment on Veterans Health Administration Enrollees'
      Behavioral Health Services Use.
AB  - OBJECTIVE: To examine Veterans Health Administration (VA) enrollees' use of VA
      services for treatment of behavioral health conditions (BHCs) after gaining
      Medicaid, and if VA reliance varies by complexity of BHCs. DATA SOURCES/STUDY
      SETTING: VA and Medicaid Analytic eXtract utilization data from 31 states, 2006
      2010. STUDY DESIGN: A retrospective, longitudinal study of Veterans enrolled in
      VA care in the year before and year after enrollment in Medicaid among 7,249
      nonelderly Veterans with serious mental illness (SMI), substance use disorder
      (SUD), posttraumatic stress disorder (PTSD), depression, or other BHCs. DATA
      COLLECTION/EXTRACTION METHODS: Utilization and VA reliance (proportion of care
      received at VA) for BH outpatient and inpatient services in unadjusted and
      adjusted analyses. PRINCIPAL FINDINGS: In adjusted analyses, we found that
      overall Veterans did not significantly change their use of VA outpatient BH
      services after Medicaid enrollment. In beta-binomial models predicting VA BH
      outpatient reliance, veterans with SMI (IRR = 1.38, p < .05), PTSD (IRR = 1.62, p
      < .01), and depression (IRR = 1.36, p < .05) had higher reliance than veterans
      with other BHCs after Medicaid enrollment. CONCLUSIONS: While veterans did not
      change the amount of VA outpatient BH services they used after enrolling in
      Medicaid, the proportion of care they received through VA or Medicaid varied by
      BHC.

PMID- 30298567
TI  - Parallel evolution of gene classes, but not genes: Evidence from Hawai'ian
      honeycreeper populations exposed to avian malaria.
AB  - Adaptation in nature is ubiquitous, yet characterizing its genomic basis is
      difficult because population demographics cause correlations with nonadaptive
      loci. Introduction events provide opportunities to observe adaptation over known
      spatial and temporal scales, facilitating the identification of genes involved in
      adaptation. The pathogen causing avian malaria, Plasmodium relictum, was
      introduced to Hawai'i in the 1930s and elicited extinctions and precipitous
      population declines in native honeycreepers. After a sharp initial population
      decline, the Hawai'i 'amakihi (Chlorodrepanis virens) has evolved tolerance to
      the parasite at low elevations where P. relictum exists, and can sustain
      infection without major fitness consequences. High-elevation, unexposed
      populations of 'amakihi display little to no tolerance. To explore the genomic
      basis of adaptation to P. relictum in low-elevation 'amakihi, we genotyped 125
      'amakihi from the island of Hawai'i via hybridization capture to 40,000
      oligonucleotide baits containing SNPs and used the reference 'amakihi genome to
      identify genes potentially under selection from malaria. We tested for outlier
      loci between low- and high-elevation population pairs and identified loci with
      signatures of selection within low-elevation populations. In some cases, genes
      commonly involved in the immune response (e.g., major histocompatibility complex)
      were associated with malaria presence in the population. We also detected several
      novel candidate loci that may be implicated in surviving malaria infection (e.g.,
      beta-defensin, glycoproteins and interleukin-related genes). Our results suggest
      that rapid adaptation to pathogens may occur through changes in different immune
      genes, but in the same classes of genes, across populations.

PMID- 30298568
TI  - Predictors of nonalcoholic steatohepatitis and significant fibrosis in non-obese
      nonalcoholic fatty liver disease.
AB  - AIMS: We compared (a) demographic and clinical characteristics and (b)
      determinants of nonalcoholic steatohepatitis and significant fibrosis in non
      obese and obese nonalcoholic fatty liver disease. METHODS: A cross-sectional
      study of 664 Asian subjects (mean age 53.1 years; men 50.3%) with biopsy-proven
      nonalcoholic fatty liver disease and controls was conducted. Subjects were
      divided by their body mass index into obese (body mass index >=25 kg/m2 ) and non
      obese (body mass index <25 kg/m2 ). RESULTS: Observations in subjects with non
      obese nonalcoholic fatty liver disease were in between non-obese controls and
      subjects with obese nonalcoholic fatty liver disease for body mass index,
      sagittal abdominal diameter, aminotransferase levels, insulin resistance and
      abdominal visceral adipose tissue area. There was no significant difference in
      histology between non-obese and obese subjects with nonalcoholic fatty liver
      disease except for lower grade of hepatic steatosis in nonobese nonalcoholic
      fatty liver disease and higher severity of hepatic fibrosis in nonobese
      nonalcoholic steatohepatitis. Predictors of nonalcoholic steatohepatitis in
      nonobese subjects included females (odds ratio 2.49), higher alanine
      aminotransferase (odds ratio 1.03), lower high-density lipoprotein cholesterol
      (odds ratio 0.96), higher prevalence of diabetes (odds ratio 3.65) and higher
      visceral adipose tissue area (odds ratio 1.63 per standard deviation increase of
      visceral adipose tissue area) while age (odds ratio 1.04), higher aspartate
      aminotransferase (odds ratio 1.02), diabetes (odds ratio 2.76) and higher
      visceral adipose tissue area (odds ratio 1.57 per standard deviation increase)
      were associated with significant fibrosis in the non-obese. Sagittal abdominal
      diameter was independently associated with nonalcoholic steatohepatitis or
      significant fibrosis among subjects with non-obese nonalcoholic fatty liver
      disease. CONCLUSION: While there were a few phenotypic differences from obese
      subjects, non-obese subjects with nonalcoholic fatty liver disease displayed a
      similar severity of histological liver damage. Potential factor(s) beyond obesity
      may play a role as non-obese nonalcoholic fatty liver disease advances to more
      severe disease.

PMID- 30298569
TI  - Facilitation from an intraspecific perspective - stress tolerance determines
      facilitative effect and response in plants.
AB  - Plant-plant interactions are reciprocal and include effects on and response to
      neighbours. Distinct traits confer competitive effect and response ability, but
      how specific traits determine effect and response in facilitative interactions
      has not been studied experimentally. We utilized the model species Arabidopsis
      thaliana to test for trait dependence of facilitative interactions. Salt
      sensitive (sos) mutants or salt-tolerant wild-types were exposed to an
      experimental salinity gradient with and without intraspecific neighbours and the
      intensity of plant-plant interactions was measured for three performance
      variables. We tested whether salt tolerance can predict facilitative effect and
      response and whether a tradeoff exists between competitive ability and tolerance
      to stress. Interactions shifted very clearly from negative to positive with
      increasing stress. Salt-sensitive genotypes were less negatively affected by
      competition but more dependent on facilitation than were wild-types, indicating a
      tradeoff between competitive ability and stress tolerance. Surprisingly,
      sensitive genotypes imposed stronger facilitative effects, despite being much
      smaller under stress, probably because they retrieved more salt from the soil.
      Stress tolerance defined facilitative effect and response via distinct
      mechanisms. We advocate more controlled experiments with model species to advance
      our understanding of the trait dependence of biotic interactions and their
      consequences for community organization.

PMID- 30298570
TI  - A viral reckoning: viruses emerge as essential manipulators of global ecosystems.

PMID- 30298571
TI  - W361R mutation in GaaR, the regulator of D-galacturonic acid-responsive genes,
      leads to constitutive production of pectinases in Aspergillus niger.
AB  - Polysaccharides present in plant biomass, such as pectin, are the main carbon
      source for filamentous fungi. Aspergillus niger naturally secretes pectinases to
      degrade pectin and utilize the released monomers, mainly D-galacturonic acid. The
      transcriptional activator GaaR, the repressor of D-galacturonic acid utilization
      GaaX, and the physiological inducer 2-keto-3-deoxy-L-galactonate play important
      roles in the transcriptional regulation of D-galacturonic acid-responsive genes,
      which include the genes encoding pectinases. In this study, we described the
      mutations found in gaaX and gaaR that enabled constitutive (i.e., inducer
      independent) expression of pectinases by A. niger. Using promoter-reporter
      strains (PpgaX-amdS) and polygalacturonic acid plate assays, we showed that W361R
      mutation in GaaR results in constitutive production of pectinases. Analysis of
      subcellular localization of C-terminally eGFP-tagged GaaR/GaaRW 361R revealed
      important differences in nuclear accumulation of N- versus C-terminally eGFP
      tagged GaaR.

PMID- 30298573
TI  - Integrating risk and dangerousness in specific legal contexts: Clarifying
      concepts and justifying interventions.
AB  - Several legal interventions under the police power and parens patriae functions
      of the state depend partially on judgments that an individual is dangerous.
      Psychological research regarding risk assessment can provide relevant evidence
      regarding the appropriate application of these interventions. Developing,
      interpreting, and presenting relevant research regarding risk assessment in a
      manner that enhances the ability of courts to make accurate determinations of
      dangerousness requires clarification of the risk presented by this individual and
      explanation of how this person generates this risk. Testimony regarding such
      research can enhance the ability of the courts to make accurate judgments
      regarding the relationship between the risk presented and the justification for
      the specific intervention at issue. This article examines the justificatory
      functions of judgments of dangerousness for various police power and parens
      patriae interventions in order to clarify the manner in which psychological
      research and testimony can contribute to the ability of the courts to accurately
      assess the risk presented by an individual in making a judgment of dangerousness
      for a specific form of legal intervention.

PMID- 30298572
TI  - Anti-inflammatory disease-modifying treatment and disability progression in
      primary progressive multiple sclerosis: a cohort study.
AB  - BACKGROUND AND PURPOSE: Treatment options in primary progressive multiple
      sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti
      inflammatory agents have failed to show efficacy in ameliorating disability
      progression. The aim of this study was to investigate a potential effect of anti
      inflammatory disease-modifying treatment on disability outcomes in PPMS. METHODS:
      Using MSBase, a large, international, observational database, we identified
      patients with PPMS who were either never treated or treated with a disease
      modifying agent. Propensity score matching was used to select subpopulations with
      similar baseline characteristics. Expanded Disability Status Scale (EDSS)
      outcomes were compared with an intention-to-treat and an as-treated approach in
      paired, pairwise-censored analyses. RESULTS: Of the 1284 included patients, 533
      were matched (treated, n = 195; untreated n = 338). Median on-study pairwise
      censored follow-up was 3.4 years (quartiles 1.2-5.5). No difference in the hazard
      of experiencing 3-month confirmed EDSS progression events was observed between
      the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6-1.7, P =
      0.87]. We did not find significant differences in the hazards of confirmed EDSS
      improvement (HR, 1.0; 95% CI, 0.6-1.6, P = 0.91) or reaching a confirmed EDSS
      step >=7 (HR, 1.1; 95% CI, 0.7-1.6, P = 0.69). CONCLUSION: Our pooled analysis of
      disease-modifying agents suggests that these therapies have no substantial effect
      on short- to medium-term disability outcomes in PPMS.

PMID- 30298574
TI  - Transcatheter arterial embolisation in four dogs with hepatocellular carcinoma.
AB  - Four dogs with hepatocellular carcinoma were treated by transcatheter arterial
      embolisation. In all dogs, the tumour-supplying arteries were selectively
      embolised with gelatine sponge particles. Post-embolisation tumour volumes
      decreased relative to pre-embolisation volumes in all dogs. No adverse reactions
      were observed in three dogs after treatment but one dog showed pancreatitis.
      These results suggest that transcatheter arterial embolisation is a feasible
      treatment for dogs with hepatocellular carcinoma.

PMID- 30298575
TI  - Development of a comprehensive infection control program for a short-term shelter
      serving trafficked women.
AB  - A shelter for trafficked women has unique infection control needs that require a
      comprehensive infection control plan, balancing the needs of infection prevention
      with respect for the vulnerable population served. Using a trauma-informed model
      and evidence from infection control in other shelter settings, a group of senior
      baccalaureate students developed a program in a short-term shelter for
      commercially sexually exploited individuals that included a written infection
      control manual, policies and procedures, and staff training. This partnership
      between academia and a nonprofit agency was an experiential service learning
      project in the domain of public health nursing, allowing students the opportunity
      to apply evidence toward a sustainable intervention for the agency.

PMID- 30298576
TI  - Extracellular Hsp70 modulates the inflammatory response of cigarette smoke
      extract in NCI-H292 cells.
AB  - NEW FINDINGS: What is the central question of this study? Does extracellular heat
      shock protein 70 (eHsp70) alter cigarette smoke extract (CSE)-induced
      inflammatory responses in NCI-H292 bronchial epithelial cells? What is the main
      finding and its importance? eHsp70 modulates inflammatory responses and TLR2,
      TLR4 and Hsp70 gene expression, and protects NCI-H292 cells against CSE-induced
      cytotoxicity. eHsp70 might be implicated in development of inflammatory diseases
      affected by cigarette smoke, such as COPD. ABSTRACT: One of the major risk
      factors for development of chronic obstructive pulmonary disease (COPD) is
      cigarette smoke. Extracellular Hsp70 (eHsp70) is increased in sera of COPD
      patients, and can act as damage-associated molecular pattern (DAMP). In this
      study, we explored inflammatory parameters (cytokine concentrations, Toll-like
      receptor (TLR) 2 and 4 and Hsp70 expression, mitogen-activated protein kinases
      (MAPKs) and nuclear factor kappaB (NF-kappaB) activation, and cytotoxicity) after
      exposure of bronchial-epithelial NCI-H292 cells to cigarette smoke extract (CSE)
      alone (2.5 and 15%) and in combinations with recombinant human (rh) Hsp70 (0.3, 1
      and 3 MUg ml-1 ). We applied specific MAPKs, NF-kappaB and Hsp70 inhibitors to
      elucidate rhHsp70 inflammation-associated responses. CSE alone and combinations
      of 15% CSE with rhHsp70 stimulated IL-1alpha, IL-6 and IL-8 release. However,
      rhHsp70 applied with 2.5% CSE decreased secretion of cytokines indicating
      antagonistic effects. Individual and combined treatments with 2.5% CSE suppressed
      TLR2 expression. CSE at 15% induced TLR2 and TLR4 gene expression, whereas
      rhHsp70 abolished that effect. rhHsp70 and 15% CSE alone reduced, while their
      combination increased, intracellular Hsp70 mRNA level. CSE alone and in
      combination with rhHsp70 activated extracellular signal-regulated kinase and p38
      MAPKs, while inhibition of MAPKs, NF-kappaB and Hsp70 attenuated IL-6 and IL-8
      secretion. CSE at 15% reduced cell viability and induced apoptosis, as shown by
      MTS and caspases-3/7 assays. CSE at 2.5% alone stimulated lactate dehydrogenase
      release, but cellular membrane integrity remained intact in co-treatments with
      rhHsp70. rhHsp70 might modulate the inflammatory response of CSE and could also
      protect NCI-H292 cells against CSE cytotoxicity. Those effects are implemented
      via MAPK and NF-kappaB signalling pathways.

PMID- 30298577
TI  - Transesophageal Echocardiographic Measurements of the Superior Vena Cava for
      Predicting Fluid Responsiveness in Patients Undergoing Invasive Positive Pressure
      Ventilation.
AB  - OBJECTIVES: Preoperative fasting, water deprivation, and intraoperative fluid
      loss and redistribution result in hypovolemia in patients undergoing surgery.
      Some findings have indicated that the superior vena cava (SVC) diameter and
      variation, as determined by transesophageal echocardiography during surgery, do
      not reflect central venous pressure effectively. This study aimed to compare and
      correlate the SVC diameter and variation with the stroke volume variation for
      predicting fluid responsiveness in patients undergoing invasive positive pressure
      ventilation. METHODS: Thirty-six patients scheduled for elective gastrointestinal
      surgery under general anesthesia with invasive positive pressure ventilation were
      included in this study. After anesthesia induction, the stroke volume variation,
      SVC diameter, mean arterial pressure, central venous pressure, and pulse were
      recorded, and measurements after fluid challenge were recorded as well. The SVC
      variation was calculated before and after the fluid challenge. RESULTS: After the
      fluid challenge, the SVC diameter markedly increased, whereas the SVC variation
      and stroke volume variation significantly decreased (P < .05). The optimal cutoff
      value for the SVC variation was 21.1%, and the area under the curve (AUC) from a
      receiver operating characteristic curve analysis was 0.849. The optimal cutoff
      value for the minimal SVC diameter was 1.135 cm, and that AUC was 0.929. In
      addition, the optimal cutoff value for the maximal SVC diameter was 1.480 cm, and
      the AUC was 0.862. CONCLUSIONS: The minimal SVC diameter may be an effective
      indicator for predicting fluid responsiveness in patients undergoing invasive
      positive pressure ventilation.

PMID- 30298578
TI  - Ultrasound for detecting postoperative pulmonary complications.

PMID- 30298579
TI  - Pre-operative hypertension and intra-operative hypotension: a reply.

PMID- 30298580
TI  - Pre-operative hypertension and intra-operative hypotension.

PMID- 30298581
TI  - Magnetic resonance safety of the Freestyle Libre glucose monitoring system.

PMID- 30298582
TI  - Neuromuscular blocking agents and intubation: a reply.

PMID- 30298584
TI  - Neuromuscular blocking agents and intubation.

PMID- 30298583
TI  - In-vitro analysis of a novel 'add-on' silicone cuff to improve sealing properties
      of tracheal tubes.
AB  - Leakage of colonised oropharyngeal secretions across the tracheal tube cuff may
      cause iatrogenic pulmonary infection. We studied a novel 'add-on' cuff, which can
      be inserted over an existing tracheal tube and advanced into the subglottic
      region. The physical properties of the novel silicone cuff (BronchoGuard, Ciel
      Medical, USA) were evaluated in comparison with the Hi-Lo(r) tracheal tube. In a
      bench study, we identified saline inflation volumes required to transmit
      pressures between 15 and 30 cmH2 O against artificial tracheas of 18, 20 and 22
      mm internal diameter. We computed cuff compliance, and minimal inflation volume
      to achieve air sealing during mechanical ventilation. Finally, we compared the
      leakage flow rate of artificial saliva across the novel cuff. On average, the
      mean (SD) inflation volumes necessary to transmit tracheal pressures of 15, 20,
      25 and 30 cmH2 O were 4.1 (2.2), 4.4 (2.3), 4.6 (2.4) and 4.8 (2.4) ml for the
      novel cuff and 7.7 (2.5), 8.0 (2.6), 8.4 (2.6) and 8.7 (2.7) ml for the Hi-Lo
      tube, respectively (p < 0.001). The minimal inflation volumes to achieve air
      sealing were 3.8 (0.9) and 10.5 (2.1) ml (p < 0.001), which resulted in
      transmitted tracheal pressures of 8.3 (9.8) and 27.6 (34.8) cmH2 O (p < 0.001).
      Compliance was 0.026 (0.004) and 0.616 (0.324) ml.cmH2 0-1 , respectively (p <
      0.001). Although massive leak was found when the novel cuff transmitted pressures
      <= 20 cmH2 O against the trachea, leakage was avoided with pressures >= 25 cmH2
      O, owing to optimal contact between the cuff and the tracheal wall. In contrast,
      the standard cuff consistently leaked irrespective of the pressure. We conclude
      that the novel cuff has advantageous properties that warrant clinical
      corroboration.

PMID- 30298585
TI  - Normalised lean weight and drug doses for obese patients.

PMID- 30298586
TI  - Ultrasound for detecting postoperative pulmonary complications: a reply.

PMID- 30298588
TI  - Burst oxygen hose.

PMID- 30298587
TI  - Bowel cancer surgery outcomes and pre-operative cardiopulmonary exercise testing:
      insights from real-world data.

PMID- 30298589
TI  - Periodontal ligament-associated protein-1 gets involved in experimental
      periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Periodontal ligament-associated protein-1 (PLAP-1) is
      an important regulator of osteogenic differentiation of periodontal ligament
      cells and plays important role in the homeostasis of periodontal tissues. But the
      role of PLAP-1 in periodontitis is poorly understood. Expressions of PLAP-1 in
      experimental periodontitis are observed to elucidate whether PLAP-1 gets involved
      in the pathogenesis of periodontitis. MATERIAL AND METHODS: Wistar rats were
      randomly allocated to two groups (n = 6/group): Ligation group and Control group.
      PLAP-1 expression in experimental periodontitis was assessed by
      immunohistochemistry and collagen fibers in periodontal ligament were observed
      using picrosirius red staining. Expressions of PLAP-1 and CD68 in periodontitis
      were colocalized by double-labelled immunofluorescence. To further examine the
      relationship between PLAP-1 and osteoclastogenesis in experimental periodontitis,
      acute periodontal inflammatory infiltration and alveolar bone destruction were
      induced by administering ligated rats with 10 ng/mL tumor necrosis factor alpha
      (TNF-alpha; ligation + TNF-alpha group, n = 6). Alveolar bone loss was observed
      by micro-computed tomography (Micro-CT), and osteoclasts were identified by
      tartrate-resistant acid phosphatase staining (TRAP). Expressions of PLAP-1 in TNF
      alpha stimulated human periodontal ligament cells were also detected at 24 and 48
      hours by western blotting. RESULTS: PLAP-1 expression levels in periodontal
      ligament cells and collagen fibers were lower in the ligation group,compared with
      the control group. Similarly, TNF-alpha decreased PLAP-1 expression in human
      periodontal ligament cells in vitro. Degradation or destruction of collagen
      fibers accompanied the reduced PLAP-1 expression in the periodontal ligament in
      the ligation group. Colocalization of PLAP-1 and CD68 revealed the positive
      relationship between PLAP-1 and CD68+ infiltrating cells in periodontitis. More
      PLAP-1-positive inflammatory cells were found in the ligation + TNF-alpha group,
      compared with the ligation + saline group. CONCLUSION: PLAP-1-positive
      inflammatory cells are involved in the pathogenesis of periodontitis. An increase
      in PLAP-1-positive inflammatory cell number contributes periodontal inflammation
      and alveolar bone loss.

PMID- 30298590
TI  - Characterization and comparison of neutrophil extracellular traps in gingival
      samples of periodontitis and gingivitis: A pilot study.
AB  - BACKGROUND AND OBJECTIVE: Neutrophil extracellular traps (NETs) are a recently
      discovered antimicrobial mechanism used by neutrophils that have been proposed as
      an intervention in the pathogenesis of periodontitis. The objective of our study
      was to characterize the expression of NETs in gingival tissues with periodontitis
      and controls and to compare the expression of these traps in gingival tissue
      samples of patients with gingivitis and periodontitis. MATERIAL AND METHODS: An
      observational cross-sectional study was conducted on patients with periodontitis,
      gingivitis, and controls that needed tooth extraction. Gingival tissue biopsies
      were gathered after clinical examination and tooth extraction. Electron
      microscopy and immunofluorescence were performed to characterize NETs, comparing
      periodontitis and control patients. Immunohistochemical analysis was performed to
      quantify neutrophil extracellular trap expression through extracellular
      citrullinated histone H3 and myeloperoxidase in biopsies from patients with
      gingivitis and periodontitis. RESULTS: Thirteen biopsies were gathered from 13
      patients: five gingivitis, six periodontitis, and two controls. Electron
      microscopy and immunofluorescence imaging showed greater expression of
      neutrophils present in periodontal inflamed tissue compared with controls.
      Release of nuclear content to the extracellular space was observed, compatible
      with the formation of NETs. The expression of citrullinated histone H3 was higher
      in gingivitis samples than periodontitis samples (P = 0.0106). Myeloperoxidase
      expression was higher in periodontitis than gingivitis, but without achieving
      statistical significance. CONCLUSION: Neutrophil extracellular traps were found
      in tissue samples of periodontitis as extracellular components of chromatin,
      along with neutrophil enzymes, that were not present in healthy controls. The
      comparison of NETs expression in periodontitis and gingivitis showed higher
      expression in gingivitis, associating them to acute phases of the periodontal
      inflammatory process.

PMID- 30298591
TI  - Can Doppler echocardiography estimate raised pulmonary capillary wedge pressure
      provoked by passive leg lifting in suspected heart failure?
AB  - AIMS: Non-invasive estimation of left ventricular filling pressure (LVFP) during
      stress is important for explaining exertional symptoms in patients with heart
      failure (HF). The aim of this study was to evaluate ability of Doppler
      echocardiographic measures of elevated LVFP with passive leg lifting (PLL) in
      patients with suspected HF. METHODS: Twenty-nine patients with clinical signs of
      HF who underwent simultaneous Doppler echocardiography and right heart
      catheterization (RHC) at rest and during PLL were consecutively investigated.
      Seventeen patients had normal PCWP (<=15 mmHg) at rest and during PLL and 12 with
      normal PCWP at rest but >15 mmHg with PLL. Conventional echo and 2D strain were
      used to assess early diastolic blood flow velocity (E), LV strain rate during
      early diastole (LVSRe), left atrial SR during atrial contraction (LASRa) and
      myocardial tissue Doppler velocities to assess lateral e' and further calculate
      E/e' and E/LVSRe and their relationship with PCWP, at rest and during PLL.
      RESULTS: Resting LAVI (beta = 0.45, P = 0.009) and LASRa (beta = -0.51, P =
      0.004) were independently related to PCWP during PLL. Also, LASRa (beta = -0.77,
      P<0.001), E/e' (beta = 0.40, P = 0.04) and E/LVSRe (beta = 0.47, P = 0.021)
      during PLL correlated with PCWP during PLL. Multiple regression analysis
      identified E/LVSRe (beta = 0.46, P = 0.001) and LASRa (beta = -0.58, P = 0.002)
      during PLL as being independently associated with PCWP during PLL. CONCLUSION:
      Left atrial volume and myocardial contraction (LASRa) at rest both predict
      unstable LV filling pressures measured as raised PCWP when provoked by PLL.
      Furthermore, LASRa at PLL seems to have the strongest association to PCWP during
      PLL.

PMID- 30298592
TI  - The comparison of an acellular matrix graft with an autologous venous graft in
      the surgical treatment of Peyronie's disease.
AB  - The aim of this study was to evaluate acellular porcine pericardium (APP) and
      compared the results with those obtained from venous grafts in the surgical
      management of Peyronie's disease (PD). An APP (Group 1) and an autologous
      saphenous vein graft (Group 2) were used in 27 and 26 patients, respectively for
      Peyronie's correction. The patients' age, body mass index (BMI), operation time,
      duration of follow-up, preoperative and postoperative IIEF-5 scores, plaque size
      and loss of sensation were evaluated in both groups. There were no differences
      between the two groups in terms of age, BMI, follow-up period, and preoperative
      and postoperative IIEF-5 scores. The postoperative IIEF-5 scores were higher than
      the preoperative IIEF-5 scores in both groups. The operation time was
      significantly longer in Group 2 than in Group 1. The duration of sensation loss
      was shorter in Group 1 compared to Group 2. Penile shortening was similar in both
      groups.

PMID- 30298593
TI  - Self-expandable sirolimus-eluting stents compared to second-generation drug
      eluting stents for the treatment of the left main: A propensity score analysis
      from the SPARTA and the FAILS-2 registries.
AB  - OBJECTIVES: To compare the effectiveness and safety of self-expandable, sirolimus
      eluting Stentys stents (SES) and second-generation drug-eluting stents (DES-II)
      for the treatment of the unprotected left main (ULM). BACKGROUND: SES may provide
      a valuable option to treat distal ULM, particularly when significant caliber gaps
      with side branches are observed. METHODS: Patients from the multicenter SPARTA
      (clinicaltrials.gov: NCT02784405) and FAILS2 registries were included. Propensity
      score with matching was performed to account for the lack of randomization.
      Primary end-point was the rate of major adverse cardiovascular events (MACE, a
      composite of all cause death, myocardial infarction, target lesion
      revascularization [TLR], unstable angina and definite stent thrombosis [ST]).
      Single components of MACE were the secondary end-points. RESULTS: Overall, 151
      patients treated with SES and 1270 with DES-II were included; no differences in
      MACE rate at 250 days were observed (9.8% vs. 11.5%, P = 0.54). After propensity
      score with matching, 129 patients treated with SES and 258 with DES-II, of which
      about a third of female gender, were compared. After a follow-up of 250 days,
      MACE rate did not differ between the two groups (9.9% vs. 8.5%, P = 0.66), as
      well as the rate of ULM TLR (1.6% vs. 3.1%, P = 0.36) and definite ST (0.8% vs.
      1.2%, P = 0.78). These results were consistent also when controlling for the
      treatment with provisional vs. 2-stents strategies for the ULM bifurcation.
      CONCLUSION: SES use for ULM treatment was associated with a similar MACE rate
      compared to DES-II at an intermediate-term follow-up. SES might represent a
      potential option in this setting.

PMID- 30298594
TI  - Metabolic covariance networks combining graph theory measuring aberrant
      topological patterns in mesial temporal lobe epilepsy.
AB  - OBJECTIVE: We aimed to study the networks' mechanism of metabolic covariance
      networks in mesial temporal lobe epilepsy (mTLE), through examining the brain
      value of fluorine-18-fluorodeoxyglucose positron emission tomography (18 F-FDG
      PET). METHODS: 18 F-FDG-PET images from 16 patients with mTLE were analyzed using
      local and global metabolic covariance network (MCN) approaches, including whole
      metabolic pattern analysis (WMPA), hippocampus-based (h-) MCN, whole brain (w-)
      MCN, and edge-based connectivity analysis (EBCA). RESULTS: WMPA showed a typical
      ipsilateral hypometabolism and contralateral hypermetabolism pattern to epileptic
      zones in mTLE. h-MCN revealed decreased hippocampus-based synchronization in
      contralateral regions. w-MCN exhibited a disrupted metabolic network with
      globally increased small-world properties and regionally decreased nodal metrics
      in the ipsilateral hemisphere. Hippocampus (h)-EBCA and whole brain EBCA (w-EBCA)
      both detected a reduced-connectivity dominated metabolic covariant network.
      Moreover, the reduced interhemisphere connectivity seemingly played a major role
      in the aberrant epileptic topological pattern. CONCLUSION: From a metabolic point
      of view, we demonstrated the damaging effects with reduced contralateral
      intranetwork metrics properties and the compensatory effects in contralateral
      intranetworks with increased network properties. However, the import role of
      significant reduced interhemisphere connection has rarely been reported in other
      mTLE studies. Taken together, 18 F-FDG-PET MCN analysis provides new evidence
      that the mTLE is a system neurological disorder with disrupted networks.

PMID- 30298595
TI  - Simultaneous perfusion and permeability assessments using multiband multi-echo
      EPI (M2-EPI) in brain tumors.
AB  - PURPOSE: To study a multiband multi-echo EPI (M2-EPI) sequence for dynamic
      susceptibility contrast (DSC) perfusion imaging with leakage correction and
      vascular permeability measurements, and to evaluate the benefits of increased
      temporal resolution provided by this acquisition strategy on the accuracy of
      perfusion and permeability estimations. METHODS: A novel M2-EPI sequence was
      developed, and a pharmacokinetic model accounting for contrast agent
      extravasation was used to produce perfusion maps and additional vascular
      permeability maps. The advantage of M2-EPI for DSC perfusion imaging was
      demonstrated in vivo in 5 patients with brain tumors, and numerical simulations
      were performed to evaluate the advantage of improved temporal resolution afforded
      by the technique. RESULTS: In contrast to underestimations of cerebral blood
      volume (CBV) in tumors using the single-echo acquisition strategy, M2-EPI
      provided more plausible estimates of CBV. A quantitative evaluation showed higher
      estimated values of CBV and mean transit time in tumor tissues using M2-EPI (CBV:
      3.08 +/- 0.78 mL/100 g versus 1.56 +/- 1.38 mL/100 g [P = .006]; mean transit
      time: 4.94 +/- 1.17 seconds versus 1.83 +/- 2.06 seconds [P = 0.033]). Numerical
      simulations showed that higher temporal resolution provided by M2-EPI was
      associated with more accurate estimates of cerebral blood flow, CBV, and
      permeability parameters. CONCLUSION: The novel M2-EPI acquisition strategy for
      DSC imaging facilitates leakage-corrected perfusion measurements with additional
      permeability assessments and more accurate estimates of perfusion/permeability
      parameters, and may be used as a quantitative tool for the diagnosis, prognosis,
      and treatment monitoring of brain tumors.

PMID- 30298596
TI  - Decision-making in dentistry related to temporomandibular disorders: a 5-yr
      follow-up study.
AB  - Temporomandibular disorders (TMDs) are common, but many patients with such
      disorders go undetected and under-treated. Our aim was to evaluate the outcome of
      using a screening tool (5 yr after it was first implemented), on the clinical
      decision-making for patients with TMDs. Adults who attended for a dental check-up
      at the Public Dental Health Services in Vasterbotten, Sweden, answered three
      screening questions (3Q/TMD) on frequent jaw pain, pain on jaw function, and
      catching/locking of the jaw. The dental records of a random sample of 200
      individuals with at least one positive response to 3Q/TMD (3Q screen-positive
      patients) and 200 individuals with all negative responses (3Q screen-negative
      patients) were reviewed for TMD-related treatment decisions. A clinical decision
      related to TMD was absent in 45.5% of 3Q screen-positive patients. Treatment of
      TMDs was associated with a positive response to the screening question on jaw
      pain (OR = 6.7, 95% CI: 3.2-14.0) and was more frequent among 3Q screen-positive
      patients (24%) than among 3Q screen-negative patients (2%; OR = 15.5, 95% CI: 5.5
      43.9), just as a female examiner was associated with more frequent treatment of
      TMDs (OR = 3.1, 95% CI: 1.2-8.4). The results indicate under-treatment of TMD
      within general dental practice and that male clinicians are less likely to
      initiate TMD treatment.

PMID- 30298597
TI  - Analysis of Pseudomonas putida growth on non-trivial carbon sources using
      transcriptomics and genome-scale modelling.
AB  - Pseudomonas putida is characterized by a versatile metabolism and stress
      tolerance traits that allow the bacterium to cope with different environmental
      conditions. In this work, the mechanisms that allow P. putida KT2440 to grow in
      the presence of four sole carbon sources (glucose, citrate, ferulic acid, serine)
      were investigated by RNA sequencing (RNA-seq) and genome-scale metabolic
      modelling. Transcriptomic data identified uptake systems for the four carbon
      sources, and candidates were subjected to preliminary experimental
      characterization by mutant strain growth to test their involvement in substrate
      assimilation. The OpdH and BenF-like porins were involved in citrate and ferulic
      acid uptake respectively. The citrate transporter (encoded by PP_0147) and the
      TctABC system were important for supporting cell growth in citrate; PcaT and VanK
      were associated with ferulic acid uptake; and the ABC transporter AapJPQM was
      involved in serine transport. A genome-scale metabolic model of P. putida KT2440
      was used to integrate and analyze the transcriptomic data, identifying and
      confirming the active catabolic pathways for each carbon source. This study
      reveals novel information about transporters that are essential for understanding
      bacterial adaptation to different environments.

PMID- 30298598
TI  - Fisher's influence on me.
AB  - This is the 100th year anniversary of Fisher's 1918 paper "The correlation
      between relatives on the supposition of Mendelian inheritance" (Transactions of
      the Royal Society of Edinburgh 1918, 52 pp 899-438). Fisher's work has had a
      strong influence on today's genetic epidemiology and this brief autobiographical
      note highlights a few of the ways his influence on me has affected the field.
      Although I once took a course of lectures from Fisher, it was mainly his writings
      that influenced my statistical thinking. Not only did the concept of maximum
      likelihood appeal to me, but also the concepts of interclass and intraclass
      correlations, discriminant analysis, and transforming semiquantitative scores to
      minimize interactions-all topics I first learned about from the 11th edition of
      his book on Statistical Methods for Research Workers. This, together with a few
      serendipitous events that shaped my career, had a large influence on me and hence
      also on the field of genetic epidemiology.

PMID- 30298600
TI  - Hunter Cancer Research Symposium 2018, 1st November 2018, Hunter Medical Research
      Institute, Kookaburra Circuit, New Lambton Heights, NSW, Australia.

PMID- 30298599
TI  - MPV17 mutations in juvenile- and adult-onset axonal sensorimotor polyneuropathy.
AB  - MPV17 encodes a putative channel-forming protein of the inner mitochondrial
      membrane and is involved in mitochondrial deoxynucleotide homeostasis. MPV17
      mutations were first reported in patients with Navajo neurohepatopathy, an
      autosomal recessive mitochondrial DNA depletion syndrome, characterized by early
      onset liver failure, failure to thrive as well as central and peripheral
      neurological involvement. Recently, two patients with juvenile-onset peripheral
      sensorimotor neuropathy associated with an MVP17 c.122G>A (p.Arg41Gln) variant
      have been reported. Here, we describe five additional patients from two unrelated
      families with sensorimotor axonal neuropathy without hepatocerebral affection
      caused by homozygous MPV17 variants. Patients of the first family carried the
      known c.122G>A variant and affected individuals of the second family had a novel
      c.376-9T>G near-splice variant, which was shown to result in an in-frame deletion
      of 11 amino acids. This report provides further evidence that MPV17 mutations
      should be considered in patients with pure, non-syndromic axonal neuropathy.

PMID- 30298601
TI  - Evolution of thermal tolerance in multifarious environments.
AB  - Species extinction rates are many times greater than the direst predictions made
      two decades ago by environmentalists, largely because of human impact. Major
      concerns are associated with the predicted higher recurrence and severity of
      extreme events, such as heat waves. Although tolerance to these extreme events is
      instrumental to species survival, little is known whether and how it evolves in
      natural populations, and to what extent it is affected by other environmental
      stressors. Here, we study physiological and molecular mechanisms of thermal
      tolerance over evolutionary times in multifarious environments. Using the
      practice of "resurrection ecology" on the keystone grazer Daphnia magna, we
      quantified genetic and plastic differences in physiological and molecular traits
      linked to thermal tolerance in historical and modern genotypes of the same
      population. This population experienced an increase in average temperature and
      occurrence of heat waves, in addition to dramatic changes in water chemistry,
      over five decades. On genotypes resurrected across the five decades, we measured
      plastic and genetic differences in CTmax , body size, Hb content and differential
      expression of four heat shock proteins after exposure to temperature as single
      stress and in combination with food levels and insecticide loads. We observed
      evolution of the critical thermal maximum and plastic response in body size, HSP
      expression and Hb content over time in a warming only scenario. Molecular and
      physiological responses to extreme temperature in multifarious environments were
      not predictable from the response to warming alone. Underestimating the effect of
      multiple stressors on thermal tolerance can lead to wrong estimates of species
      evolvability and persistence.

PMID- 30298602
TI  - Comparative ecophysiology of Dinophysis acuminata and D. acuta (DINOPHYCEAE,
      DINOPHYSIALES): effect of light intensity and quality on growth, cellular toxin
      content, and photosynthesis1.
AB  - Dinoflagellates of the genus Dinophysis are the most persistent producers of
      lipophilic shellfish toxins in Western Europe. Their mixotrophic nutrition
      requires a food chain of cryptophytes and plastid-bearing ciliates for sustained
      growth and photosynthesis. In this study, cultures of D. acuminata and D. acuta,
      their ciliate prey Mesodinium rubrum and the cryptophyte, Teleaulax amphioxeia,
      were subject to three experimental settings to study their physiological response
      to different combinations of light intensity and quality. Growth rates, pigment
      analyses (HPLC), photosynthetic parameters (PAM-fluorometry), and cellular toxin
      content (LC-MS) were determined. Specific differences in photosynthetic
      parameters were observed in Dinophysis exposed to different photon fluxes (10-650
      MUmol photons . m-2  . s-1 ), light quality (white, blue and green), and shifts
      in light regime. Dinophysis acuta was more susceptible to photodamage under high
      light intensities (370-650 MUmol photons . m-2  . s-1 ) than D. acuminata but
      survived better with low light (10 MUmol photons . m-2  . s-1 ) and to a
      prolonged period (28 d) of darkness. Mesodinium rubrum and T. amphioxeia showed
      their maximal growth rate and yield under white and high light whereas Dinophysis
      seemed better adapted to grow under green and blue light. Toxin analyses in
      Dinophysis showed maximal toxin per cell under high light after prey depletion at
      the late exponential-plateau phase. Changes observed in photosynthetic light
      curves of D. acuminata cultures after shifting light conditions from low
      intensity-blue light to high intensity-white light seemed compatible with
      photoacclimation in this species. Results obtained here are discussed in relation
      to different spatiotemporal distributions observed in field populations of D.
      acuminata and D. acuta in northwestern Iberia.

PMID- 30298603
TI  - Emotional and behavioral problems among Jordanian adolescents: Prevalence and
      associations with academic achievement.
AB  - BACKGROUND: Mental health concerns are important for adolescent's general
      wellbeing and they can be associated with their ability to function effectively
      in various aspects of their daily life. AIM: The purpose of this study was to
      identify emotional and behavioral disorders (EBD) among Jordanian adolescents and
      their association with academic outcomes. METHODS: A descriptive correlational
      design was used. A total of 810 adolescents participated in the study and
      completed the demographic survey and the Strengths and Difficulties Questionnaire
      (SDQ). The grade point average (GPA) was used as an indicator of the academic
      achievement. The GPA was correlated with the SDQ scores to identify the
      relationship between the EBD and academic achievement. RESULTS: About 11.7% of
      the participants had psychological and behavioral problems. The most commonly
      reported problems were emotional symptoms (14.2%), conduct problems (12.5%), and
      hyperactivity (7.5%). There was a significant difference in psychological and
      behavioral problems according to the participants' gender. There was a
      significant negative relationship between the SDQ scores and the GPA. CONCLUSION:
      There is a need to identify adolescents at risk of emotional and behavioral
      difficulties and refer them to appropriate care and support, which in turn would
      improve their academic achievement.

PMID- 30298604
TI  - Managing bullying in Swedish workplace settings: A concealed and only partially
      acknowledged problem.
AB  - AIM: The purpose of this article was to explore workplace routines and strategies
      for preventing and managing bullying in the context of health and elderly care.
      BACKGROUND: Bullying is a serious problem in workplaces with consequences for the
      individual, the organisation and the quality of care. METHOD: Open-ended
      interviews were conducted with 12 participants, including managers and
      specialists within one hospital and three municipalities. The interviews were
      analysed with qualitative content analysis. RESULTS: Bullying was often
      concealed, due to avoidance, unclear definition and lack of direct strategies
      against bullying. No preventative work focusing on bullying existed. Psychosocial
      issues were not prioritized at workplace meetings. The supervisor had the formal
      responsibility to identify, manage and solve the bullying problem. The most
      common decision to solve the problem was to split the group. CONCLUSIONS: The
      findings showed that bullying was a concealed problem and was first acknowledged
      when the problem was acute. IMPLICATIONS FOR NURSING MANAGEMENT: Crucial
      strategies to prevent and combat bullying consist of acknowledgement of the
      problem, transformational leadership, prioritization of psycho-social issues,
      support of a humanistic value system and work through bullying problems to
      achieve long-term changes.

PMID- 30298605
TI  - Humic substances reduce ruminal methane production and increase the efficiency of
      microbial protein synthesis in vitro.
AB  - BACKGROUND: In ruminants, enteric CH4 represents a major energy loss for the host
      and is a potent greenhouse gas that contributes to climate change. Previous
      studies have shown that humic substances (HS) may have beneficial effects on
      livestock nutrition. The present study investigated the effects of HS on in vitro
      CH4 production and rumen fermentation. RESULTS: Total gas production was linearly
      increased with increasing HS after 12 h of incubation, although it was unaffected
      after 24 and 48 h. Increasing HS linearly decreased CH4 at all time points.
      Increasing HS linearly decreased NH3 -N concentration and the molar proportion of
      acetate at 12 h, whereas the efficiency of microbial protein (MP) production and
      total dry matter digestibility (TDMD) linearly increased, with starch digestion
      (SD) responding quadratically. After 48 h, HS linearly increased MP and TDMD,
      with neutral detergent fibre digestibility responding quadratically. CONCLUSION:
      Inclusion of HS effectively reduced CH4 production and increased substrate
      disappearance and the efficiency of microbial protein synthesis in vitro.
      However, its effect on in vivo CH4 production, rumen fermentation and ruminant
      production requires further investigation. (c) 2018 Society of Chemical Industry.

PMID- 30298606
TI  - Scale development: Chinese Irrational Beliefs and Rational Attitude Scale.
AB  - University study has been considered to be one of the most stressful periods in a
      person's life. University students may have irrational beliefs that could play a
      significant role in causing emotional disturbance. Nevertheless, a suitable
      instrument for measuring irrational beliefs in college students in Chinese
      society has been lacking. The aim of this study was to construct a culturally
      relevant scale for measuring irrational beliefs among university students in the
      Hong Kong Chinese context. The construction of the Chinese Irrational Beliefs and
      Rational Attitude Scale (CIBRAS) for university students was based on (1)
      literature review and expert panel review for evaluation on content validity, (2)
      a pilot test of 200 local Hong Kong university students to determine the scale's
      psychometric properties and probe the exploratory factor analysis, and (3)
      confirmatory factor analysis to test for construct validity of the CIBRAS
      (conducted with a further 655 local Hong Kong university students). The results
      showed that the five-factor 19-item CIBRAS has good psychometric properties,
      including good internal consistency (Cronbach's alphas ranging from .64 to .80),
      content validity (content validity index = .96 for relevance, .94 for clarity,
      and .94 for representativeness), construct validity (explaining 60.1% of the
      total variance), and adequate fit indices (normed chi-square = 2.8, comparative
      fit index = .94, normal fit index = .93, non-normed fit index = .93, incremental
      fit index = .94, root-mean-square error of approximation = .077, and standardized
      root-mean residual = .074). The limitations and implications of the study were
      discussed.

PMID- 30298607
TI  - Necrotizing enterocolitis attenuates developmental heart rate variability
      increases in newborn rats.
AB  - BACKGROUND: We have shown previously that a decreased high-frequency spectrum of
      heart rate variability (HF-HRV), indicative of reduced vagal tone, shows promise
      in predicting neonates likely to develop necrotizing enterocolitis (NEC) before
      its clinical onset. We hypothesized that NEC induction in rat pups decreases HF
      HRV power; subdiaphragmatic vagotomy worsens the severity of the NEC phenotype,
      increases levels of pro-inflammatory cytokines, and alters the myenteric
      phenotype. METHODS: Newborn Sprague-Dawley rats, representative of preterm human
      neonates, were subjected to 7-8 days of brief periods of cold stress and hypoxia
      to induce NEC with or without unilateral subdiaphragmatic vagotomy. HRV was
      measured at postnatal days one and five, pups were sacrificed at day 8/9, and
      gastrointestinal tissues and blood were collected for immunohistochemical,
      corticosterone, and cytokine analysis. KEY RESULTS: Compared to control, NEC
      induced rats showed the following: (a) typical histological signs of grade 2 NEC,
      which were more severe in rats that underwent vagotomy; (b) reduced developmental
      increases in time (RMSSD) and frequency (HF) HRV spectra when combined with the
      stress of laparotomy/vagotomy; (c) increases in nitric oxide synthase
      immunoreactivity in the myenteric plexus of jejunum and ileum; furthermore,
      compared to mild NEC and controls, vagotomized NEC rats had increased plasma
      values of pro-inflammatory cytokines IL-1beta and IL-6. CONCLUSIONS AND
      INFERENCES: Our data suggest that in rodents, similar to neonatal observations,
      NEC induction attenuated developmental HF-HRV increases, furthermore,
      subdiaphragmatic vagotomy worsened the histological severity, increased pro
      inflammatory cytokines, and altered the nitrergic myenteric phenotype, suggesting
      a role of the vagus in the development of NEC pathology.

PMID- 30298608
TI  - Benefit of early versus deferred antiretroviral therapy on progression of liver
      fibrosis among people with HIV in the START randomized trial.
AB  - BACKGROUND: The role of antiretroviral therapy (ART) in reducing or contributing
      to liver fibrosis in persons with HIV is unclear. We evaluated participants in
      the Strategic Timing of AntiRetroviral Treatment trial (START) for liver fibrosis
      using the AST to platelet ratio index (APRI) and Fibrosis-4 Index (FIB-4), and
      assessed for a benefit of early versus delayed antiretroviral therapy (ART) on
      liver fibrosis progression. DESIGN AND INTERVENTION: ART-naive persons with high
      CD4 counts (>500 cells/MUL) from 222 clinical sites in 35 countries were
      randomized to receive ART either at study enrolment (immediate treatment arm) or
      when their CD4 count fell below 350 cells/MUL (deferred treatment arm). The
      following outcomes were evaluated: fibrosis (APRI>0.5 or FIB-4>1.45), significant
      fibrosis (APRI>1.5 or FIB-4>3.25), hepatic flare, and resolution of elevated APRI
      and FIB-4 scores. RESULTS: Of the 4684 enrolled into the START study, 104 did not
      have APRI or FIB-4 results and were excluded. Among 4580 participants (2273
      immediate treatment; 2307 deferred treatment), the median age was 36 years, 26.9%
      were female, and 30.4% were black. Three percent had an alcoholism or substance
      abuse history, 6.4% had hepatitis, and 1.1% had significant fibrosis at baseline.
      The median CD4 count was 651 and 5.3% had HIV RNA<=200. Immediate arm
      participants were at lower risk of developing increased fibrosis scores than
      deferred arm participants (hazard ratio [HR]=0.66; 95% confidence interval
      [CI]=0.57-0.78; p<0.001), and more likely to have resolution of elevated baseline
      scores (HR 1.6; 95% CI 1.3-1.9; p<0.001). CONCLUSIONS: Significant liver fibrosis
      was rare among ART-naive HIV-positive persons with high CD4 counts. Our findings
      suggest a benefit of early ART in preventing the development of liver fibrosis.
      This article is protected by copyright. All rights reserved.

PMID- 30298609
TI  - Vertical Step-Growth Polymerization Driven by Electrochemical Stimuli from an
      Electrode.
AB  - We present herein the vertical step-growth polymerization of a monomer A-B
      through individual A-A or B-B coupling driven by electrochemical switching of
      positive and negative bias on a self-assembled A or B electrode. The monomer RuII
      (bda)AB (bda=2,2'-bipyridine-6,6'-dicarboxylate), in which A and B are pyridine
      moieties with pendant carbazolyl and vinyl groups, could be dimerized at
      oxidative (ca. 1.0 V vs. Ag/Ag+ ) or reductive potential (ca. -1.8 V) to give a
      self-assembled RuII (bda)PA or RuII (bda)PB monolayer (P=pyridine with a pendant
      phosphonic acid) on ITO glass. This polymerization enabled the sequence- and
      topology-controlled synthesis of surface-confined molecular wires with single
      molecule precision on an electrode. The electrocatalytic performance of the
      vertically orientated molecular wires for water oxidation increased with
      increasing molecular length and exceeded that of both the self-assembled
      monolayer and a randomly electropolymerized film, which have previously been
      studied as typical models.

PMID- 30298610
TI  - Developing a critical trans gerontology.
AB  - Within existing academic literature, ageing within trans populations has
      primarily been addressed from the perspective of offering advice to service
      providers and clinicians, with relatively limited application of critical
      sociological perspectives. This article seeks to integrate the critical
      perspectives on gerontology with transfeminism, identifying areas of commonality
      regarding accounts of an integrated lifecourse, scepticism of biomedicalization,
      and an emphasis on local context. The article suggests that this integration
      provides a fruitful basis for developing future research into the study of trans
      ageing, and also provides theoretical development across many debates around age,
      gender and the lifecourse.

PMID- 30298611
TI  - Cluster capture-recapture to account for identification uncertainty on aerial
      surveys of animal populations.
AB  - Capture-recapture methods for estimating wildlife population sizes almost always
      require their users to identify every detected animal. Many modern-day wildlife
      surveys detect animals without physical capture-visual detection by cameras is
      one such example. However, for every pair of detections, the surveyor faces a
      decision that is often fraught with uncertainty: are they linked to the same
      individual? An inability to resolve every such decision to a high degree of
      certainty prevents the use of standard capture-recapture methods, impeding the
      estimation of animal density. Here we develop an estimator for aerial surveys, on
      which two planes or unmanned vehicles (drones) fly a transect over the survey
      region, detecting individuals via high-definition cameras. Identities remain
      unknown, so one cannot discern if two detections match to the same animal;
      however, detections in close proximity are more likely to match. By modeling
      detection locations as a clustered point process, we extend recently developed
      methodology and propose a precise and computationally efficient estimator of
      animal density that does not require individual identification. We illustrate the
      method with an aerial survey of porpoise, on which cameras detect individuals at
      the surface of the sea, and we need to take account of the fact that they are not
      always at the surface. This article is protected by copyright. All rights
      reserved.

PMID- 30298612
TI  - Impact of the systematic use of the Gugging Swallowing Screen in patients with
      acute ischaemic stroke.
AB  - BACKGROUND AND PURPOSE: Post-stroke dysphagia occurs in up to three quarters of
      patients with acute stroke and is associated with a higher risk of respiratory
      infections and poor outcome. Systematic screening of dysphagia in the acute
      stroke unit is essential to identify patients at risk of aspiration and to
      provide dietary recommendations. Our study aimed to assess the impact of the
      systematic application of the Gugging Swallowing Screen (GUSS) in patients with
      acute ischaemic stroke. METHODS: This was a retrospective study of consecutive
      patients with acute ischaemic stroke admitted to an acute stroke unit in two time
      periods: pre-GUSS (February 2014-July 2015), when the 10-mL water-swallowing test
      was systematically administered, and GUSS (August 2015-October 2016), when the
      GUSS test was systematically administered. Groups were compared with regard to
      baseline and stroke characteristics, and the occurrence of stroke-associated
      pneumonia (SAP), in-hospital death and 3-month outcome. RESULTS: Of the 344
      patients who were included in the study (median age 71 years), 51.7% were male
      with a median National Institutes of Health Stroke Scale score of 11. A total of
      204 patients were included during the pre-GUSS period and 140 during the GUSS
      period. Patients in the GUSS period more frequently had diabetes and partial
      anterior circulation syndromes, and were more frequently treated with
      thrombectomy. There was no difference in the occurrence of SAP between the two
      groups (pre-GUSS, 12.5%; GUSS, 15.1%; P = 0.490) and no differences were found
      concerning in-hospital mortality (P = 0.996), 3-month functional independence (P
      = 0.647) or 3-month mortality (P = 0.598). CONCLUSIONS: The systematic
      administration of GUSS in a population of patients with acute ischaemic stroke
      did not reduce the occurrence of SAP, mortality or 3-month functional dependence
      when compared with the systematic administration of the 10-mL water-swallowing
      test.

PMID- 30298613
TI  - Life-sentenced juveniles: Public perceptions of risk and need for incarceration.
AB  - Pursuant to recent United States Supreme Court decisions in Miller v. Alabama
      (2012) and Montgomery v. Louisiana (2016), individuals convicted of crimes
      committed when they were younger than 18 and for which they received mandatory
      life sentences are entitled to new sentencing hearings. This study examined
      public perceptions of such individuals (life-sentenced juveniles, or LSJs). Study
      participants were 663 adults (52.3% male) ages 22-71 years (M = 36.00, SD =
      11.46) recruited using Amazon Mechanical Turk (MTurk). Each participant received
      one of a possible four vignettes about a man who was incarcerated for a crime
      that occurred when he was 17 years old and subsequently sentenced to mandatory
      life in prison following conviction. Two variables (risk of harming others if
      released to the community, and circumstances of the crime) were manipulated in a
      2 * 2 between-subjects design. Each participant read one vignette and then
      answered questions relating to appropriateness for release from prison. Results
      indicate that risk, but not circumstances of the crime, strongly influenced
      participants' views regarding resentencing. When the individual in the vignette
      was labeled as high risk, participants described him as less appropriate for
      release, more deserving of punishment, needing more rehabilitation, and more
      appropriate for specific and general deterrence. The circumstances of the crime
      had no effect on participants' responses. This may be important for various
      reasons, as applicable law does not explicitly identify risk as a consideration
      in juvenile resentencing. The nonetheless noteworthy empirical influence of risk
      on perceptions regarding LSJs is discussed in their implications for research,
      policy, and practice.

PMID- 30298614
TI  - Views of Appropriate Use Criteria for catheterization and percutaneous coronary
      revascularization by practicing interventional cardiologists: Results of a survey
      of American College of Cardiology Interventional Section members.
AB  - OBJECTIVES: The American College of Cardiology (ACC) Interventional Section
      Council leadership sought to examine the views of interventional cardiologists
      regarding the practical implementation and the value of the Appropriate Use
      Criteria (AUC) in their clinical practice. BACKGROUND: The ACC AUC for
      revascularization were originally intended to assess trends in revascularization
      patterns by hospitals and physicians to ensure that both under- and over
      utilization were minimized. As a quality assurance tool, the AUC were designed to
      allow physicians to obtain insight into their practice patterns and improve their
      practice. Recent trends toward tying payment to performance have raised concerns
      that these criteria will be incorrectly applied to individual patient
      reimbursement, which is not what they were designed to do. Consequently, the AUC
      have become controversial, not for their value in quality assessment, but for the
      manner in which agencies have used the AUC as a tool to potentially deny payment
      for certain patients. METHODS: Utilizing an online survey, members of the ACC
      Interventional Section were queried regarding the use of AUC, how they use them,
      and how they feel utilization impacts the care of patients. RESULTS: We found
      substantial variability in how the AUC were utilized and concern regarding the
      value of AUC. Among our findings was that respondents were split (51% vs 49%)
      regarding the value of AUC to patients and/or their laboratory. CONCLUSIONS: In
      this article, we discuss the implications of these findings and consider options
      on how AUC might be made a better-accepted and more impactful tool for clinicians
      and patients.

PMID- 30298615
TI  - Eye movements during reading in Parkinson's disease: A pilot study.

PMID- 30298616
TI  - First chemical and sensory characterization of Moribel and Tinto Fragoso wines
      using HPLC-DAD-ESI-MS/MS, GC-MS, and Napping(r) techniques: comparison with
      Tempranillo.
AB  - BACKGROUND: Due to the current dominance of a few grape varieties in the wine
      market, the aim of this work was to study the detailed phenolic and volatile
      composition, chromatic characteristics, and sensorial properties of red wines
      elaborated with new Vitis vinifera grapes (Moribel and Tinto Fragoso) identified
      using the High Perfomance Liquid Chromatography-Diode Array Detector-Electrospray
      Ionization-Tandem Mass Spectrometry (HPLC-DAD-ESI-MS/MS), Gas Chromatography-
      Mass Spectrometry (GC-MS), CIELab color space, and Napping (r) techniques.
      RESULTS: Tinto Fragoso wine showed higher phenolic content than Moribel, with
      more anthocyanins, flavonols, and stilbenes. These wines also contained
      anthocyanin diglucosides not reported for Vitis vinifera wines. The odor activity
      values of free volatile compounds were calculated to indicate their influence on
      wine aroma, the fruity aromas of Moribel standing out particularly. The wines
      studied were positively evaluated by the tasters. Moribel's sensory profile was
      characterized by red fruit aromas and Tinto Fragoso showed more aromatic
      intensity and persistence in the mouth. CONCLUSION: The results obtained from the
      first characterization of red wines made from novel Vitis vinifera grapes suggest
      that Moribel and Tinto Fragoso could be appropriate raw materials for the
      elaboration of quality young red wines. Tinto Fragoso provided wines with
      sensorial properties different from those of Tempranillo, and could be an
      alternative to the well known red wines on the market. (c) 2018 Society of
      Chemical Industry.

PMID- 30298617
TI  - Rapid prediction of chlorophylls and carotenoids content in tea leaves under
      different levels of nitrogen application based on hyperspectral imaging.
AB  - BACKGROUND: Photosynthetic pigments perform critical physiological functions in
      tea plants. Their content is an essential indicator of photosynthetic efficiency
      and nutritional status. The present study aimed to predict chlorophyll a (Chl a),
      chlorophyll b (Chl b), total chlorophyll (total Chl), and carotenoid (Car)
      content in tea leaves under different levels of nitrogen treatment using
      hyperspectral imaging (HSI) in combination with variable selection algorithms.
      RESULTS: A total of 150 samples were collected and scanned using the HSI system.
      The mean spectrum in the region of interest (ROI) was extracted, and the pigment
      content was measured by traditional chemical methods. Five and seven optimal
      wavelengths (OWs) were selected using the regression coefficients (RCs) of
      partial least squares regression (PLSR) and the second-derivative (2-Der),
      respectively. The optimal 2-Der-PLSR models for Chl a, Chl b, total Chl, and Car
      performed remarkably well based on seven OWs with correlation coefficients of
      prediction (RP ) of 0.9337, 0.9322, 0.9333 and 0.9036, root mean square errors in
      prediction (RMSEP) of 0.1100, 0.0511, 0.1620, and 0.0300 mg g-1 , respectively.
      CONCLUSION: The results of this study revealed that HSI combined with variable
      selection method can be employed as a rapid and accurate method for predicting
      the content of pigments in tea plants. (c) 2018 Society of Chemical Industry.

PMID- 30298618
TI  - Target-site mutation accumulation among ALS-inhibitor-resistant Palmer amaranth.
AB  - BACKGROUND: Palmer amaranth (Amaranthus palmeri S. Wats) is one of the most
      common and troublesome weeds in the USA. Palmer amaranth resistance to ALS
      inhibitors is widespread in the USA as in Arkansas. The cross-resistance patterns
      and mechanism of resistance are not known. Experiments were conducted to (1)
      determine cross-resistance to ALS-inhibitors and (2) identify target-site
      mutations in 20 Palmer amaranth localities from 13 counties in Arkansas. RESULTS:
      All Palmer amaranth localities tested had plants cross-resistant to imazethapyr,
      flumetsulam, primisulfuron, pyrithiobac, and trifloxysulfuron. The dose of
      trifloxysulfuron that caused 50% control was 21- to 56-fold greater for resistant
      accessions than susceptible ones. All but three resistant plants analyzed had one
      or two relative copies of ALS; one plant had seven relative copies. All resistant
      plants tested (18 localities) carried the Trp574 Leu mutation, which is known to
      confer broad resistance to ALS inhibitors, supporting the cross-resistance
      pattern observed. Besides Trp574 Leu mutation, 30% of localities had individuals
      with one additional resistance-conferring mutation including either Ala122 Thr,
      Pro197 Ala, or Ser653 Asn. CONCLUSION: Trp574 Leu mutation in ALS is the primary
      mechanism of resistance to ALS inhibitors in Palmer amaranth from Arkansas, USA.
      In some localities, multiple mutations have accumulated in one plant. All
      localities tested contained plants with resistance to five families of ALS
      inhibitors. Localities with extreme high resistance to ALS inhibitors, and those
      outside of the subset we studied, may harbor non-target site resistance
      mechanisms. ALS inhibitors are generally no longer effective on Palmer amaranth
      in these localities from the US mid-south. This article is protected by
      copyright. All rights reserved.

PMID- 30298619
TI  - Enhanced Production of High-Value Cyclopropane Fatty Acid in Yeast Engineered for
      Increased Lipid Synthesis and Accumulation.
AB  - The unique strained ring structure in cyclopropane fatty acids (CFA) conveys
      oxidative stability and lubricity to lipids. These attributes are highly valuable
      for industrial applications such as cosmetics and specialist lubrication but
      there is currently no commercial source of the lipid. Here, built on recently
      engineered strains of Saccharomyces cerevisiae, the authors have developed an
      efficient strategy for CFA production. Expression of the Escherichia coli
      cyclopropane fatty acid synthetase (Ec.CFAS) in the engineered yeast resulted in
      formation of cis-9,10-methylene-hexadecanoic and octadecanoic acids in both the
      phospholipid (PL) and triacylglycerol (TAG) fractions. CFA concentration in TAG
      of engineered yeast is 12 mg CFA g-1 DCW (fourfold above the strain expressing
      CFAS only). The yield of CFA increases from 13.2 to 68.3 mg L-1 , the highest
      reported in yeast, using a two-stage bioprocess strategy that separated cell
      growth from the lipid modification stage. Strategies for further improvement of
      this valuable lipid are proposed.

PMID- 30298620
TI  - Protective effects of omega-3 fatty acids against Alzheimer's disease in rat
      brain endothelial cells.
AB  - OBJECTIVES: Omega-3 fatty acids are well-known unsaturated fatty acids that are
      essential for growth and development in animals. They primarily participate in
      the development of intelligence, the nervous system, and vision, and the
      metabolism of neurotransmitters. Omega-3 fatty acids have been widely studied in
      the treatment of Alzheimer's disease (AD). Omega-3 fatty acids are known to have
      neuroprotective effects due to their antioxidant capacity. Rotenone has been
      shown to induce neurotoxicity in vitro. METHODS: We investigated the protective
      effects of omega-3 fatty acids against AD in rat brain microvascular endothelial
      cells (RBMVECs) in vitro. Lipid peroxidation, reactive oxygen species (ROS),
      glutathione peroxidase (Gpx), reduced glutathione (GSH), superoxide dismutase
      (SOD), and catalase levels were evaluated in RBMVECs. Flow cytometry was
      performed to assess apoptosis. RESULTS: Lipid peroxidation and ROS were reduced
      in RBMVECs following incubation with omega-3 fatty acids. Catalase, Gpx, and SOD
      were increased in RBMVECs following incubation with omega-3 fatty acids. Flow
      cytometry showed that incubation with omega-3 fatty acids reduced the amount of
      apoptotic RBMVECs. CONCLUSION: Our results suggest that omega-3 fatty acids show
      potential as a therapeutic agent against AD.

PMID- 30298621
TI  - Switching the manufacturer of antiepileptic drugs is associated with higher risk
      of seizures: A nationwide study of prescription data in Germany.
AB  - OBJECTIVE: Despite bioequivalence, the exchangeability of antiepileptic drugs in
      clinical settings is disputed. Therefore, we investigated the risk for recurrent
      seizures after switching the manufacturer of the same drug in a large German
      cohort. METHODS: Anonymous patient data from practice neurologists throughout
      Germany between 2011 and 2016 were collected using the IMS Disease Analyzer
      database (QuintilesIMS, Frankfurt, Germany). People with epilepsy were included
      if at least 2 prescriptions within 360 days and 1 within 180 days prior to the
      index date were available. The cohort was separated into a seizure group and
      seizure-free controls. Both groups were matched 1:1 according to age, gender,
      insurance status, and treating physician. The risk for breakthrough seizures
      after a manufacturer switch of the same antiepileptic drug was analyzed using
      multivariate regression models. RESULTS: A total of 3,530 people with epilepsy
      were included (each group, n = 1,765; age = 53.7 +/- 19.8 years). Patients with
      seizures had switched the drug manufacturer more often than controls (26.8% vs
      14.2%; odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.08-1.69, p =
      0.009), both from branded to generic (5.5% vs 2.4%; OR = 1.85, 95% CI = 1.30
      2.64, p < 0.001) and between generic drugs (14.7% vs 7.1%; OR = 1.45, 95% CI =
      1.13-1.87, p = 0.004). INTERPRETATION: In previously seizure-free patients,
      switching the manufacturer of antiepileptic medications was associated with a
      higher risk for seizure recurrence. Our retrospective approach does not allow us
      to determine whether other changes in medical care at the same time could
      contribute to the recurrence. However, it would be prudent to avoid switching the
      manufacturer of anticonvulsants in seizure-free patients. Ann Neurol 2018.

PMID- 30298622
TI  - High prevalence of congenital deafness on Reunion Island is due to a founder
      variant of LHFPL5.
AB  - Reunion Island is a French oversea department in the Indian Ocean with 1.6/1000,
      an estimated prevalence of deafness that is almost double as compared to the
      mainland France. Twelve children having isolated bilateral prelingual profound
      deafness along with motor delay attributed to vestibular areflexia were enrolled.
      Their mean walking age was 19 months. Electroretinography and temporal bone CT
      scans were normal in all cases. A novel homozygous frameshift lipoma HMGIC fusion
      partner-like 5 (LHFPL5) variant c.185delT p.(Phe62Serfs*23) was identified using
      whole-exome sequencing. It was found in seven families. Four patients from two
      different families from both Reunion Island and mainland France, were compound
      heterozygous: c.185delT p.(Phe62Serfs*23) and c.472C > T p.(Arg158Trp). The
      phenotype observed in our patients completely mimics the hurry-scurry (hscy)
      murine Tmhs knock-out model. The recurrent occurrence of same LHFPL5 variant in
      Reunion Island is attributed to common ancestor couple born in 1693.

PMID- 30298623
TI  - Creation of Centimeter-Sized 2 D Crystalline Film by Crystallization of
      Homopolymer in Solution.
AB  - The 2 D assembly of polymers to form free-standing and large crystalline films is
      quite appealing but very challenging. Although there have been some works using
      interface templates, reports of in situ assembly in solution are still rare.
      Herein, a simple strategy is developed for the creation of a free-standing and
      centimeter-sized 2 D crystalline polymer film through crystallization of an
      amphiphilic brush polydiacetylene (PDA) in solution. The film exhibits good shape
      memory, a low dielectric constant, and good carrier mobility. This strategy may
      be applied extensively to produce a variety of other macroscopic 2 D crystalline
      polymer films for applications in electronics, catalysis, and so on.

PMID- 30298624
TI  - Digital evaluation of marginal and internal fit of single-crown fixed dental
      prostheses.
AB  - The present study used a new, digitized version of the impression replica
      technique, namely the dual-scan technique, to evaluate the adaptation of single
      crown fixed dental prostheses (FDPs). Scans of the bare master model and of the
      master model with a silicone layer representing the cement layer were
      superimposed and analyzed using designated software. Single crowns produced using
      the lost-wax metal casting technique were included. The cement space of the band
      width, 0.5-1.0 mm from the preparation margin (marginal fit), was smallest for
      crowns made from laser-sintered cobalt-chromium. The internal fit in both mesial
      distal and buccal-palatal directions was statistically significantly better for
      crowns made using the conventional lost-wax metal casting technique than for
      crowns produced using computer-aided design/computer-aided manufacturing
      (CAD/CAM). Fixed dental prostheses produced by milled cobalt-chromium had the
      loosest internal fit. The results agree with those of our previous study of the
      same test specimens, in which the triple-scan method was used, and imply that the
      dual-scan method is well suited for adaptation studies.

PMID- 30298625
TI  - Cardiopulmonary exercise testing for evaluation of a randomized exercise training
      intervention following aortic valve replacement.
AB  - Aortic valve surgery is the definitive treatment for aortic stenosis (AS). No
      specific recommendation is available on how exercise training should be conducted
      and evaluated after aortic valve replacement (AVR). This study aimed to examine
      the effect of aerobic exercise training on exercise capacity following AVR. In
      addition to our primary outcome variable, peak oxygen uptake (peakVO2 ), the
      effect on submaximal cardiopulmonary variables including oxygen uptake kinetics
      (tau), oxygen uptake efficiency slope (OUES) and ventilatory efficiency (VE/VCO2
      slope) was evaluated. Following AVR due to AS, 12 patients were randomized to
      either a group receiving 12 weeks of supervised aerobic exercise training (EX) or
      a control group (CON). Exercise capacity was assessed by a maximal
      cardiopulmonary exercise test (CPET). There was a significant increase in peak
      load (+28%, P = 0.031) and in peakVO2 (+23%, P = 0.031) in EX, corresponding to
      an increase in achieved percentage of predicted peakVO2 from 88 to 104% (P =
      0.031). For submaximal variables, there were only non-statistically significant
      trends in improvement between CPETs in EX. In CON, there were no significant
      differences in any maximal or submaximal variable between CPETs. We conclude that
      12 weeks of supervised aerobic exercise training induces significant adaptations
      in cardiopulmonary function following AVR, especially in regard to maximal
      variables including peakVO2 . In addition, we provide novel data on the effect on
      several submaximal variables following exercise training in this group of
      patients.

PMID- 30298626
TI  - Dietary nutrient levels alter the metabolism of arginine family amino acids in
      the conceptus of Huanjiang mini-pigs.
AB  - BACKGROUND: The arginine family amino acids (AFAAs) exert important roles in the
      metabolism, growth and development of the conceptus. However, to date, few
      studies have investigated the effects of maternal nutrient levels on the
      concentrations and metabolism of AFAAs in the conceptus. RESULTS: Compared to low
      nutrient diets, high nutrient diets increased (P < 0.05) the concentrations of
      citrulline and proline (Pro) in plasma; the concentrations of arginine,
      glutamine, Pro and ornithine (Orn) in the amniotic fluid; and the concentrations
      of all detected AFAAs in the allantoic fluid, which were most pronounced on day
      45 of pregnancy. High nutrient diets upregulated (P < 0.05) mRNA expression of
      arginase I (Arg I), Pro oxidase and spermidine synthetase (SRM) in the fetal
      placenta, as well as Arg II, SRM and spermine synthetase (SMS) expression in the
      fetal liver (most pronounced on day 45 of pregnancy). The same effect was
      observed for mRNA expression of NO synthase and Orn aminotransferase (OAT),
      mainly on day 110 of pregnancy, and for mRNA expression of Arg I, Arg II, OAT,
      Orn decarboxylase and SMS throughout pregnancy. High nutrient diets upregulated
      (P < 0.05) mRNA expression of Y+ L-type amino acid transporter (LAT) and cationic
      amino acid transporter 1 (CAT1) in the fetal jejunum throughout pregnancy.
      Dietary treatments did not affect (P > 0.05) mRNA expression of Y+ LAT1, sodium
      coupled neutral amino acid transporter 2 (SNAT2) and CAT1 in the fetal placenta,
      skeletal muscle and colon. CONCLUSION: High nutrient diets increased the
      concentration and transport of AFAAs in the mothers and conceptus, which likely
      improves growth and development of the conceptus. (c) 2018 Society of Chemical
      Industry.

PMID- 30298628
TI  - Piggyback implantable collamer lens implantation for the correction of residual
      refractive errors after cataract surgery: a multicenter study.

PMID- 30298627
TI  - Abnormal Fasting Glucose Increases Risk of Unrecognized Myocardial Infarctions in
      an Elderly Cohort.
AB  - OBJECTIVES: To investigate glucose levels as a risk factor for unrecognized
      myocardial infarctions (UMIs). DESIGN: Cohort SETTING: Cardiovascular Health
      Study. PARTICIPANTS: Individuals aged 65 and older with fasting glucose
      measurements (N=4,355; normal fasting glucose (NFG), n = 2,041; impaired fasting
      glucose (IFG), n = 1,706; DM: n = 608; 40% male, 84% white, mean age 72.4 +/-
      5.6). MEASUREMENTS: The relationship between glucose levels and UMI was examined.
      Participants with prior coronary heart disease (CHD) or UMI on initial
      electrocardiography were excluded. Using Minnesota codes, UMI was identified
      according to the presence of pathological Q-waves or minor Q-waves with ST-T
      abnormalities. Crude and adjusted hazard ratios (HRs) were calculated. Analyses
      were adjusted for age, sex, body mass index (BMI), hypertension, antihypertensive
      and lipid-lowering medication use, total cholesterol, high-density lipoprotein
      cholesterol, and smoking status. RESULTS: Over a mean follow-up of 6 years, there
      were 459 incident UMIs (NFG, n=202; IFG, n=183; DM, n=74). Participants with IFG
      were slightly more likely than those with NFG to experience a UMI (hazard ratio
      (HR)=1.11, 95% confidence interval (CI)=0.91-1.36, p = .30), and those with DM
      were more likely than those with NFG to experience a UMI (HR=1.65, 95% CI=1.25
      2.13, p < .001). After adjustment HR for UMI in IFG those with IFG were no more
      likely than those with NFG to experience a UMI (HR=1.01, 95% CI=0.82-1.24, p =
      .93), whereas those with DM were more likely than those with NFG to experience a
      UMI (HR=1.37, 95% CI=1.02-1.81, p = .03). The 2-hour oral glucose tolerance test
      was not statistically significantly associated with UMI. CONCLUSION: Fasting
      glucose status, particularly in the diabetic range, forecasted UMI during 6 years
      of follow-up in elderly adults. Further studies are needed to clarify the level
      of glucose at which risk is greater.

PMID- 30298629
TI  - Implementing a salutogenic treatment model in a clinical setting of emergency
      child and adolescent psychiatry in Sweden.
AB  - PROBLEM: Emergency care in child and adolescent psychiatry often lacks a coherent
      treatment model. This study reports on the development and implementation of a
      salutogenic treatment model at the Child & Adolescent Psychiatric Emergency Unit
      in Malmo, Sweden. METHODS: The development and implementation involved all staff
      categories and was guided by a recognized authority on salutogenesis. Generalized
      resistance resources (GRR) were identified that could be implemented at the unit
      to improve patients' sense of coherence. FINDINGS: Eight GRR were developed and
      implemented at the unit. During the 6-month period following the implementation,
      patients (n = 41) and parents reported satisfaction with the treatment, while
      mental health improved between admission and discharge, and both treatment length
      and readmission rates were reduced. CONCLUSION: A salutogenic treatment model
      involving GRR seems to be a promising approach in child and adolescent
      psychiatric emergency treatment.

PMID- 30298630
TI  - Virtual screening of naphthoquinone analogs for potent inhibitors against the
      cancer-signaling PI3K/AKT/mTOR pathway.
AB  - The PI3K/AKT/mTOR pathway is one of the most commonly disrupted signaling
      pathways that plays a role in the development and pathogenicity of multiple
      cancers. Therefore, the critical proteins of this pathway have been targeted for
      anticancer therapy. The scientific community has increasingly been realizing the
      anti-cancer therapeutic potential of naphthoquinone analogs. These compounds
      constitute a major class of diverse sets of plant metabolites, which include
      various natural products and synthetic compounds with proven anticancer activity.
      The current study involved structural computational biology approaches to explore
      compounds from a diverse pool of naphthoquinone analogs that can inhibit key
      cancer-signaling proteins phosphoinositide 3-kinase (PI3K), protein kinase B, PKB
      (AKT), and mammalian target of rapamycin (mTOR). The novel compound identified
      commonly among the top 10 dock score lists of PI3K, AKT, and mTOR was selected
      for further study and proposed as a potential inhibitor of the 3 cancer-signaling
      proteins and an anticancer agent. Further, to check the docking accuracy and
      potential of the compound, post docking analyses, namely, binding comparison with
      the native ligand, the role of the interacting residue role in binding, predicted
      binding energy and dissociation constant calculations, etc., were performed. All
      these measures showed good-quality binding, and thus provide weight to our
      prediction of the novel compound as a pan PI3K/AKT/mTOR inhibitor and an
      anticancer agent. Finally, to compare the binding and similarity in the active
      sites of the 3 protein kinases, a ligand-based active site alignment was
      performed and analyzed. Thus, the study proposed a novel naphthoquinone analog as
      a potential anticancer drug, and provided comparative structural insight into its
      binding to the 3 protein kinases.

PMID- 30298632
TI  - 2018 Frechette Awards Announced.

PMID- 30298631
TI  - Effect of Radix isatidis polysaccharide on alleviating insulin resistance in type
      2 diabetes mellitus cells and rats.
AB  - OBJECTIVES: The objective of this paper was to explore the effects of Radix
      isatidis polysaccharide (RIP) extracted from Radix isatis on alleviating insulin
      resistance. METHODS: The insulin resistance models of 3T3-L1 preadipocytes and
      type 2 diabetic rats were established to evaluate the insulin resistance activity
      of RIP. KEY FINDINGS: Radix isatidis polysaccharide within the concentration
      range of 25-100 MUg/ml could reduce cell supernatant glucose and TNF-alpha levels
      (P < 0.01) and increase the expression of PI-3K P85, Glut4, IRS-1 and Akt protein
      in symptoms of IR 3T3-L1 preadipocytes. In the meantime, RIP contributed to
      relieve the weight loss of diabetic rats whose liver weight and liver index were
      decreased due to the effects of RIP. Experiments in rats also showed that RIP had
      capacity in reduced serum TC, TG, LDL-C, FFA, FBG, FINS, MDA, ALT, AST activities
      and increased serum HDL-C, SOD, ISI (P < 0.05 or 0.01). In addition, the oral
      glucose tolerance in rats was improved (P < 0.05) and liver damage was restored
      due to RIP. CONCLUSIONS: Radix isatidis polysaccharide significantly alleviates
      insulin resistance in 3T3-L1 preadipocytes and type 2 diabetic rats. These
      beneficial effects of RIP may associate with their roles in improving the glucose
      metabolism, lipid metabolism and oxidative stress.

PMID- 30298634
TI  - Terraced and Smooth Gradient Polymer Brushes via a Polymer Single-Crystal
      Assisted Grafting-To Method.
AB  - Gradient polymer brushes provide a spatial gradient change in molecular
      characteristics of the brush, and such a change can be utilized to study
      structure-property relationships in a combinatorial fashion. In this study, a
      bottom-up method was used to synthesize gradient polymer brushes with a
      predesigned and precisely controlled grafting density gradient and brush pattern.
      A polymer single-crystal assisted grafting-to (PSCAGT) method was employed where
      end-functionalized polymers were grown into two-dimensional polymer single
      crystals. The latter were chemically coupled to a solid substrate to form well
      defined polymer brushes. To tune the grafting density, end-dissimilar polymers
      were used to co-crystallize into one single crystal. Programmed single-crystal
      growth was introduced to synthesize brushes with two different gradient
      architectures, that is, terraced and smooth gradient with pyramid patterns. This
      work demonstrates that the PSCAGT method offers a unique means to tune polymer
      brush nanostructure.

PMID- 30298635
TI  - Detecting Counterfeit Brandies.
AB  - A hypothesis-free sensor array (optoelectronic tongue) composed of an anionic, a
      cationic and two neutral poly(para-aryleneethynylene)s (PAE) at pH 3, 7 and 13
      discriminate more than 30 spirits (including brandy, Branntwein, Cognac,
      Spirituose, and Weinbrand). Counterfeits (made by mixing of low-quality spirits
      and caramel colour) and different batches of identical brands of brandies are
      discriminated. The sensor array works without sample preparation or great
      instrumental cost, and is superior to conventional methods with respect to sample
      need (10-20 MUL), time and effort. The discrimination stems from differential
      fluorescence quenching of the PAE-array by the complex mixture of the beverages'
      colourants, from the oak barrels or added caramel colour. The collected quenching
      data were analysed by linear discriminant analysis (LDA) and principal component
      analysis (PCA) to achieve successful discrimination.

PMID- 30298636
TI  - A folic acid-enriched diet attenuates prostate involution in response to androgen
      deprivation.
AB  - BACKGROUND: Serum folate concentrations in the United States have risen since
      dietary folic acid fortification was first mandated in 1998. Although maternal
      folic acid offers protection against neural tube defects in conceptuses, its
      impact on other organ systems and life stages have not been fully examined. Here,
      we used a mouse model to investigate the impact of a Folic acid (FA) enriched
      diet on prostate homeostasis and response to androgen deprivation. METHODS: Male
      mice were fed a control diet (4 mg FA/kg feed) or a folic acid supplemented diet
      (24 mg FA/kg feed) beginning at conception and continuing through early
      adulthood, when mice were castrated. RESULTS: We made the surprising observation
      that dietary FA supplementation confers partial resistance to castration-mediated
      prostate involution. At 3, 10, and 14 days post-castration, FA enriched diet fed
      mice had larger prostates as assessed by wet weight, taller prostatic luminal
      epithelial cells, and more abundant RNAs encoding prostate secretory proteins
      than castrated control diet fed mice. Diet did not significantly affect prostate
      weights of intact mice or serum testosterone concentrations of castrated mice.
      RNA-Seq analysis revealed that the FA enriched diet was associated with a unique
      prostate gene expression signature, affecting several signaling and metabolic
      pathways. CONCLUSIONS: Continuous exposure to a FA enriched diet slows prostate
      involution in response to androgen deprivation. Prostates from FA diet mice have
      increased secretory gene expression and increased luminal cell heights. The
      influence of dietary FA supplementation on the prostate response to androgen
      deprivation raises a future need to consider how dietary folic acid
      supplementation affects efficacy of androgen-reducing therapies for treating
      prostate disease.

PMID- 30298637
TI  - Oxidative stress-induced alterations in seminal plasma antioxidants: Is there any
      association with keap1 gene methylation in human spermatozoa?
AB  - Kelch-like ECH-associated protein 1 (keap1)-nuclear factor-erythroid 2-related
      factor 2 (Nrf2) pathway is one of the master regulators of cellular defence
      against oxidative stress. Epigenetic alterations like hypermethylation of keap1
      gene impair keap1-Nrf2 system in several oxidative stress-associated diseases.
      The objective of this study was to evaluate the epigenetic status of keap1 in
      sperm DNA of normozoospermic subjects, having different levels of reactive oxygen
      species (ROS) in seminal plasma. Semen samples were obtained from 151 apparently
      healthy male partners of couples who attended the Avicenna infertility clinic.
      Samples were categorised into four groups according to their ROS levels: group A
      (n = 39, ROS < 20 RLU/s per 106 spermatozoa), group B (n = 38, 20 <= ROS < 40
      RLU/s per 106 spermatozoa), group C (n = 31, 40 <= ROS < 60 RLU/s per 106
      spermatozoa) and group D; (n = 43, ROS >= 60 RLU/s per 106 spermatozoa). Keap1
      methylation status was assessed using methylation-specific PCR along with seminal
      total antioxidant capacity. The results showed no significant alterations in
      keap1 methylation in any groups, whereas the total antioxidant capacity enhanced
      with increasing levels of ROS exposure. These results indicate that keap1 was not
      methylated during ROS elevation and oxidative stress, suggesting that the cells
      have adopted other mechanisms to elevate antioxidant level.

PMID- 30298638
TI  - Patient-Reported outcome measures and their utility in the management of patients
      with advanced chronic kidney disease.
AB  - Symptom and quality of life (QOL) measures in patients with advanced chronic
      kidney disease (CKD) are recognised indicators of patient-centred care and
      represent important research, quality and clinical measures. This study examined
      relationships between symptom burden, QOL and functional status and associations
      of symptoms and mortality risk. A multisite longitudinal cohort analysis was
      undertaken in CKD stage 4/5 (no dialysis, ND) and dialysis patients. Patients
      completed symptom and QOL measures (Palliative Care Outcome Symptom Score (POS-S
      renal) [1], World Health Organisation QOL, WHOQOL-BREF) [2] and Karnofsky
      Performance scale [3]. Clinical and demographic data were recorded. Participants
      recruited were 112 dialysis and 40 ND patients. High symptom burden was present
      and correlated with lower QOL, QOL subdomains and reduced performance status.
      Comparing groups found a small significant difference in physical QOL suggesting
      dialysis treatment burden. Further analysis was restricted comparing 102 dialysis
      and 31 CKD stage 4 (CKD4) patients. Dialysis patients had above target
      adequacies, but poorer appetite, nausea, vomiting and difficulty sleeping
      compared with CKD4 patients. Overall, the most prevalent symptoms were also the
      most severe, specifically pain, dyspnea, weakness, difficulty sleeping. Cox
      Proportional Hazards regression showed severe pain, nausea, vomiting, poor
      mobility, itch and skin changes were significantly associated with shorter
      survival in dialysis patients. Severe symptom score was associated with mortality
      risk (HR 1.1, 95%CI(1.03,1.17) compared with no increased risk with comorbidity
      score or age. Patients with advanced CKD had significant symptom burden
      correlated with poorer QOL. Symptoms may also be useful in considering clinical
      outcomes, specifically mortality. This article is protected by copyright. All
      rights reserved.

PMID- 30298639
TI  - Rapid ultrasound-assisted dispersive solid-phase extraction of nonsteroidal anti
      inflammatory drugs in urine using oleic acid functionalized magnetic graphene
      oxide.
AB  - We describe an ultrasound-assisted magnetic dispersive solid-phase extraction
      based on oleic acid functionalized magnetic graphene oxide followed by high
      performance liquid chromatography with ultraviolet detection. The method was
      applied for the simultaneous determination of ibuprofen, diclofenac, naproxen,
      and mefenamic acid in urine. The application of sonication led to the good
      dispersion of the sorbent, and consequently, significant shortened the extraction
      time. The sorbent was successfully characterized by different techniques. The
      influence of the adsorption parameters was optimized using a rotational central
      composite design. In order to improve desorption efficiency, parameters such as
      type and volume of the eluent and sonication time were investigated and optimized
      through a one variable at a time method. Under the optimum conditions, limits of
      detection and precision were between 3.0-25 ng/mL (n = 5) and 3.2-7.1%,
      respectively. The preconcentration factors were found to be 74 for naproxen, 76
      for diclofenac, 80 for ibuprofen, and 66 for mefenamic acid corresponding to the
      absolute recovery within the range of 82.5-100%. Finally, the proposed method was
      successfully applied for simultaneous determination of target analytes in human
      urine samples. The relative recovery was within the range of 91.4-113.3%,
      indicating the good reliability and accuracy of the method.

PMID- 30298641
TI  - A longitudinal study of hymenoptera stings in preschool children.
AB  - BACKGROUND: Insect venom is the second most common cause of anaphylaxis outside
      of medical encounters. Stings cause over 20% of all anaphylactic deaths and 7% of
      anaphylaxis in children. To date, there have been no longitudinal studies of
      insect sting events or allergy in preschool children. METHODS: A prospective
      longitudinal nested observational study in the BASELINE Birth Cohort Study (n =
      2137). Sting-related questions were asked at 6 and 12 months and 2 and 5 years.
      Skin prick testing (SPT) was performed at 2 and 5 years. SpIgE testing was
      performed on selected cases at 2 years. RESULTS: Seventy-seven children (6.8%)
      were stung by the age of 2. Of these, 25 (32.5%) reported adverse reactions (four
      systemic). Eleven (0.9%) had positive SPT at 2 years (eight bee, two wasp, one
      both). Four stung children had positive SPT. Two (one stung, one never stung) had
      positive spIgE to a venom component at 2 years. A total of 268 children (21.9%)
      were stung by 5 years, 144 (52.1%) reporting local reactions and none systemic.
      Four children (0.4%) had positive SPT at 5 years: one bee and three wasp. Of the
      11 SPT-positive children at 2 years, none were still positive at 5 years.
      CONCLUSION: This is the first longitudinal study of the natural history of
      hymenoptera stings and allergy in preschool children. Hymenoptera venom allergy
      is less common in this cohort than in adults. Systemic reactions were not
      medically documented in this population, in keeping with previous literature.
      This study confirms the poor correlation of IgE sensitization to venom with sting
      allergy and does not support the common parental request to screen children for
      sting allergy.

PMID- 30298642
TI  - Dropping to escape: a review of an under-appreciated antipredator defence.
AB  - Dropping is a common antipredator defence that enables rapid escape from a
      perceived threat. However, despite its immediate effectiveness in predator-prey
      encounters (and against other dangers such as a parasitoid or an aggressive
      conspecific), it remains an under-appreciated defence strategy in the scientific
      literature. Dropping has been recorded in a wide range of taxa, from primates to
      lizards, but has been studied most commonly in insects. Insects have been found
      to utilise dropping in response to both biotic and abiotic stimuli, sometimes
      dependent on mechanical or chemical cues. Whatever the trigger for dropping, the
      decision to drop by prey will present a range of inter-related costs and benefits
      to the individual and so there will be subtle complexities in the trade-offs
      surrounding this defensive behaviour. In predatory encounters, dropping by prey
      will also impose varying costs and benefits on the predator - or predators -
      involved in the system. There may be important trade-offs involved in the
      decision made by predators regarding whether to pursue prey or not, but the
      predator perspective on dropping has been less explored at present. Beyond its
      function as an escape tactic, dropping has also been suggested to be an important
      precursor to flight in insects and further study could greatly improve
      understanding of its evolutionary importance. Dropping in insects could also
      prove of significant practical importance if an improved understanding can be
      applied to integrated pest-management strategies. Currently the non-consumptive
      effects of predators on their prey are under-appreciated in biological control
      and it may be that the dropping behaviour of many pest species could be exploited
      via management practices to improve crop protection. Overall, this review aims to
      provide a comprehensive synthesis of the current literature on dropping and to
      raise awareness of this fascinating and widespread behaviour. It also seeks to
      offer some novel hypotheses and highlight key avenues for future research.

PMID- 30298640
TI  - Weaker semantic language lateralization associated with better semantic language
      performance in healthy right-handed children.
AB  - INTRODUCTION: The relationship between language abilities and language
      lateralization in the developing brain is important for our understanding of the
      neural architecture of language development. METHODS: We investigated 35 right
      handed children and adolescents aged 7-16 years with a functional magnetic
      resonance imaging language paradigm and a comprehensive language and verbal
      memory examination. RESULTS: We found that less lateralized language was
      significantly correlated with better language performance across areas of the
      brain and across different language tasks. Less lateralized language in the
      overall brain was associated with better in-scanner task accuracy on a semantic
      language decision task and out-of-scanner vocabulary and verbal fluency.
      Specifically, less lateralized frontal lobe language dominance was associated
      with better in-scanner task accuracy and out-of-scanner verbal fluency.
      Furthermore, less lateralized parietal language was associated with better out-of
      scanner verbal memory across learning, short- and long-delay trials. In contrast,
      we did not find any relationship between temporal lobe language laterality and
      verbal performance. CONCLUSIONS: This study suggests that semantic language
      performance is better with some involvement of the nondominant hemisphere.

PMID- 30298643
TI  - A Photovoice study on nurses' perceptions and experience of resiliency.
AB  - AIM: To explore the meaning of resilience to nurses and their perceived
      resilience enhancing factors. BACKGROUND: With challenges faced at work, nurses'
      professional quality of life is adversely affected with nurses experiencing
      compassion fatigue, depression, burnout and even signs of post-traumatic stress
      disorder. Degree of resilience can determine job satisfaction and nursing
      attrition. METHODS: The study adopted a descriptive qualitative design using
      Photovoice. Eight nurses from an academic medical centre in Singapore
      participated in focus group interviews and data were analysed with inductive
      content analysis approach. RESULTS: Four themes were generated: (a) resilience is
      performing nursing duties despite adversities; (b) resilience is a dynamic
      process that develops over time; (c) religion and faith help build resilience;
      and (d) support of others is important in overcoming work-related stress.
      CONCLUSIONS: Knowledge on resilience is vital to understand influencing factors
      of personal resilience and relationship to stress and burnout. Building nurses'
      resilience is significant to improve and sustain healthy and effective
      functioning of nurses. IMPLICATIONS FOR NURSING MANAGEMENT: With sufficient
      external resources and psychosocial support from hospital administrators, early
      resilience-based approach may provide the buffer and protective factor in facing
      workplace stress, to improve overall job satisfaction and improve nurses'
      retention.

PMID- 30298644
TI  - A tripartite toxin-antitoxin module induced by quorum sensing is associated with
      the persistence phenotype in Streptococcus mutans.
AB  - The oral pathogen Streptococcus mutans communicates using a canonical Gram
      positive quorum sensing system, CSP-ComDE. The CSP pheromone already known to be
      involved in the development of genetic competence positively influences the
      formation of persisters, dormant variants of regular cells that are highly
      tolerant to antimicrobial therapy. It is now believed that the persistence
      phenotype is the end result of a stochastic switch in the expression of toxin
      antitoxin (TA) modules. TAs consist of a pair of genes that encode two
      components, a stable toxin and its cognate labile antitoxin. Transcription
      analyses revealed that three core genes encoding a putative TA system, called
      SmuATR, were members of the S. mutans CSP regulon. We hypothesized that S. mutans
      is using its CSP-ComDE system as a deterministic mechanism for persister
      formation through the activation of smuATR locus. We showed here that the SmuATR
      system constitutes a novel tripartite type II TA system in which the smuA and
      smuT genes encode an antitoxin and a toxin, respectively, while SmuR is a
      transcriptional repressor involved in the autoregulation of the operon. Ectopic
      expression of SmuA - SmuT is associated with the CSP-inducible persistence
      phenotype. In contrast, overexpression of SmuT alone is bactericidal and causes
      membrane permeabilization. To our knowledge, SmuATR is the first functional
      chromosomal tripartite TA system shown to be induced by the bacterial quorum
      sensing system and involved in persister formation.

PMID- 30298645
TI  - Perspectives in renal replacement therapy: Haemodialysis.
AB  - Haemodialysis (HD) was the first procedure that had demonstrated the ability to
      partially replace renal function, and became the most widely utilized treatment
      for patients with end-stage renal disease (ESRD). In a great majority of
      countries around the world, conventional in-centre HD had become the predominant
      renal replacement therapy, being touted as able to achieve better solute
      clearance and more successful in attaining euvolemia than patients on peritoneal
      dialysis. This is despite the antecedent hemodynamic risks, more rapid loss of
      residual renal function, greater infectious perils, excessive erythropoietin
      requirements and higher infrastructure costs. In addition, quality of life had
      been suggested to be worse among patients on HD, though this had been challenged
      repeatedly. Consequently, the concept of integrated ESRD care over the last few
      decades had placed HD, as a complementary rather than a competitive treatment
      modality to the entire armamentarium of renal replacement therapies.
      Incorporating HD as part of integrated care into health-care policies and
      national resource planning will become an essential strategy in improving access
      and outcome to care among the ESRD population. The improvement in technologies
      and innovation in prescription had brought forth enhanced dialyzer membrane and
      machine upgrades, and expanded modalities including more frequent HD and
      haemodiafiltration. While boasting of controversial improvement in outcomes, many
      of these therapies remain expensive and insurmountable for widespread utility in
      many countries. In addition, the results of these new technologies had been
      conflicting across studies, with some even suggesting that they could be
      detrimental. Therefore, judicial consideration has to be undertaken to
      appropriate their use in clinical practice.

PMID- 30298646
TI  - Glomerular mesangial cell and podocyte injuries in diabetic nephropathy.
AB  - Diabetic nephropathy is one of the leading causes of end-stage renal disease and
      creates heavy healthcare burdens globally. Dysfunction of mesangial cells and
      podocytes contributes to diabetic nephropathy. Dysregulation of signaling
      involved in renal development and regeneration may cause diabetic kidney damages.
      Growing evidences suggest the importance of dysregulated dickkopf-1 (DKK1)/Wnt/
      beta-catenin signaling pathways in the pathogenesis of diabetic glomerular
      injuries. The inhibition of Wnt signaling in injured mesangial cells is likely
      attributed to the high glucose-induced Ras/Rac1 dependent superoxide formation.
      When DKK1, the cellular inhibitor of Wnt signaling, binds to the Kremen-2
      receptor, depositions of extracellular matrix increase in the mesangium of
      diabetic kidneys. Additionally, reactivation of Notch-1 signaling has been
      implicated in podocytopathy during diabetic proteinuria development. Knocking
      down Notch-1 alleviates vascular endothelial growth factor (VEGF) expression,
      nephrin repression and proteinuria in diabetic kidneys. It is also found that
      epigenetic modulations by histone deacetylase 4 (HDAC4) and miR-29a could lead to
      diabetic nephropathy. High glucose increases the expression of HDAC4, which
      causes deacetylation with subsequent ubiquitination of nephrin. Overexpression of
      miR-29a in diabetic transgenic mice would decrease the expression of HDAC4 and
      stabilize nephrin. Surprisingly, reprogramming or reactivation of signaling
      involved in renal development or regeneration often brings about diabetic
      glomerular sclerosis in mesangial cells and podocytes. Better knowledge about
      modifications of embryonic stem cell signaling will have a chance to implement
      strategically focused pharmacological research programs aiming to the development
      of new drugs for diabetic kidney injuries.

PMID- 30298647
TI  - Maternal obesity and offspring risk of chronic kidney disease.
AB  - It is increasingly recognized that maternal obesity is implicated in
      developmental programming, contributing to the future risk of chronic disease
      development in offspring. The exact mechanisms of the role of maternal obesity in
      the development of chronic kidney disease in offspring remain unclear and animal
      models used are not without limitation. Human studies are limited by the effects
      of postnatal environmental conditions, which may have a direct impact on disease
      phenotype; and animal models are limited by use of species that differ
      significantly. This review will examine the most recent evidence from animal
      models on the impact of maternal factors during pregnancy/lactation on the future
      risk of chronic kidney disease development in offspring, emphasising the role of
      maternal obesity in exacerbating the deleterious effects of diet-induced obesity
      and/or diabetes on renal health.

PMID- 30298648
TI  - Biomarkers for acute cardiorenal syndrome.
AB  - Cardiorenal syndromes are disorders of the heart and kidneys whereby dysfunction
      in one organ may lead to dysfunction in the other organ. Cardiorenal syndrome
      type I (CRS I) is defined as acute kidney injury caused by acute cardiac
      dysfunction such as acute decompensated heart failure and acute coronary
      syndrome. Traditional markers like serum creatinine may delay the diagnosis of
      acute kidney injury and provide limited information regarding the underlying
      pathophysiology in the setting of CRS I. Herein, we briefly review some emerging
      biomarkers, including brain natriuretic peptide, soluble ST2, angiopoietin,
      soluble thrombomodulin, neutrophil gelatinase-associated lipocalin, kidney injury
      molecule-1, cystatin C, interleukin-18 and calprotectin. These biomarkers may
      help early detecting, differential diagnosis, assessing disease severity and
      prognosis in patients with CRS I, therefore improve patient management and
      outcomes.

PMID- 30298649
TI  - Association between albumin and C-reactive protein and ankle-brachial index in
      haemodialysis.
AB  - AIM: Peripheral artery occlusive disease (PAOD) is associated with increased
      rates of cardiovascular mortality, morbidity and hospitalization in patients
      undergoing dialysis. An ankle-brachial index (ABI) less than 0.9 has been used to
      diagnose PAOD. The aim of this study was to evaluate associations among
      inflammation, malnutrition and their interactions on the risk of PAOD. METHODS:
      Two hundred and twenty-two haemodialysis patients (mean age 61.0 +/- 11.7 years,
      56.8% men) were enrolled and stratified into four groups according to median
      values of albumin (3.87 g/dL) and logarithm of C-reactive protein (CRP) (0.48
      mg/L). Associations between the study groups and an ABI less than 0.9 were
      assessed using multiple logistic regression analysis. Receiver operating
      characteristic curves were constructed to predict an ABI less than 0.9. RESULTS:
      A lower level of albumin and higher level of CRP were significantly associated
      with an ABI less than 0.9 in multivariate analysis (odds ratio, 5.688; 95%
      confidence interval, 1.369-23.626; P = 0.017) after adjusting for demographic,
      clinical, biochemical and medication data. The interaction between albumin and
      CRP in relation to an ABI less than 0.9 was significant in multivariate analysis
      (odds ratio, 1.797; 95% confidence interval, 1.258-2.568; P = 0.001). The areas
      under the curve for albumin, CRP and albumin + CRP for the prediction of ABI less
      than 0.9 were 0.311, 0.654 and 0.733, respectively. CONCLUSION: Patients
      undergoing haemodialysis with a lower albumin level and higher CRP level have an
      increased risk of PAOD. A combination of malnutrition and inflammation may be
      associated with PAOD in haemodialysis patients.

PMID- 30298650
TI  - Epigenetic targeting for acute kidney injury.
AB  - In recent years, epigenetics has emerged as important mechanisms for the
      regulation of pathogenesis in many diseases, including acute kidney injury (AKI).
      Numerous studies have demonstrated that AKI is associated with the changes in
      epigenetics, including histone modifications, DNA methylation and the expression
      of various non-coding RNAs. Through utilizing histone deacetylase (HDAC)
      inhibitors, studies have demonstrated that increase of histone acetylation either
      protects kidney from injury or potentiates this process, depending on which HDAC
      (s) isform is suppressed, whereas inhibition of histone methyltransferase,
      generally provides a protective effect in AKI. Although AKI is also associated
      with changes in DNA methylation, the role of DNA methylation in kidney injury
      remains unclear. In this article, we discuss the role and mechanism of histone
      acetylation and methylation in the pathogenesis of AKI.

PMID- 30298651
TI  - Raising awareness, screening and prevention of chronic kidney disease: It takes
      more than a village.
AB  - Chronic kidney disease (CKD) is a major public health problem worldwide. Its
      prevalence and incidence are increasing, particularly among the ethnic minority
      populations. Diabetes, hypertension and obesity have been the three major
      aetiologies for CKD in all developed countries. While diabetes and hypertension
      remain the major causes of CKD in developing countries, environmental pollution,
      pesticides, water, analgesic abuse and herbal medications are common causes in
      these regions. Rapid urbanization and globalization are thought to be the
      contributing factors to rising prevalence and incidents of CKD. Despite the
      rising prevalence of CKD, disease awareness remains profoundly low. Worldwide,
      only 6% of the general population and 10% of the high-risk population are aware
      of their CKD statuses. Health screenings have been shown to be effective in
      improving the incidence of ESRD. However, currently there is no effective tool to
      assess and evaluate the awareness objectively.

PMID- 30298652
TI  - Perspectives on acute kidney injury strategy: Hong Kong.
AB  - Acute kidney injury is a common condition in hospitalized patients and a strong
      predictor of short-term morbidity and mortality. In this article, local
      epidemiological data on the prevalence and outcome of acute kidney injury amongst
      hospitalized patient in a tertiary referral center were discussed. The latest
      practice guidelines endorsed by the Hong Kong College of Physicians will be
      discussed, with emphasis on local practical issues and problems of guideline
      implementation.

PMID- 30298653
TI  - Complement in glomerular diseases.
AB  - Complement activation has been identified to play a vital role in the
      pathogenesis of many glomerulonephritis, either as direct complement activation
      driven factor in thrombotic microangiopathy and C3 glomerulopathy, and/or as an
      important contributor in lupus nephritis and anti-neutrophil cytoplasmic antibody
      associated vasculitis. Recent studies indicated that complement activation may
      also play roles in the pathogenesis of immunoglobulin A nephropathy and focal
      segmental glomerulosclerosis. Interestingly, monoclonal immunoglobulins/light
      chains from patients with monoclonal gammopathy may interfere with complement
      activation and thus indirectly result in complement-mediated glomerulonephritis.
      Understanding of the pathogenic roles of complement activation in various
      glomerulonephritis will facilitate the identification of potential novel
      therapeutic targets in complement system.

PMID- 30298654
TI  - New insights into the role and mechanism of Wnt/beta-catenin signalling in kidney
      fibrosis.
AB  - Wnt/beta-catenin is an evolutionarily conserved, developmental signalling pathway
      that regulates embryogenesis, injury repair and pathogenesis of human diseases.
      Dysregulated activation of Wnt/beta-catenin is associated with the development
      and progression of renal fibrotic lesions after injury. Wnt are induced and beta
      catenin is activated in various models of experimental chronic kidney disease
      (CKD) and in human nephropathies. Recent findings indicate that pro(renin)
      receptor is an amplifier of Wnt/beta-catenin by acting as a downstream target and
      an obligatory component for its signal transduction. Genetic blockade of Wnt
      secretion in a cell type-specific manner uncovers renal tubular epithelium as the
      major source of Wnt ligands in CKD. Wnt/beta-catenin controls the expression of a
      wide variety of downstream mediators implicated in kidney fibrosis, such as
      fibronectin, Snail1, matrix metalloproteinase-7, hepatocyte growth factor and
      various components of the renin-angiotensin system. Targeted inhibition of
      Wnt/beta-catenin is able to ameliorate kidney fibrotic lesions in pre-clinical
      settings. In this review, we summarize recent advances in our understanding of
      the regulation, signal transduction, role and mechanisms of Wnt/beta-catenin
      signalling in the pathogenesis of kidney fibrosis. We also discuss the
      therapeutic potential of targeting this pathway for the treatment of fibrotic
      CKD.

PMID- 30298655
TI  - Role of C-reactive protein in the pathogenesis of acute kidney injury.
AB  - Acute kidney injury (AKI) is characterized by both non-inflammatory and
      inflammatory process, and accumulating evidence has demonstrated that
      inflammation plays a key role in the pathogenesis and progression of AKI. C
      reactive protein (CRP), an acute reactant produced by liver and many inflammatory
      cells, acts not only as an inflammation biomarker, but also as a pathogenic
      factor for AKI. Indeed, increased concentration of CRP is associated with poor
      outcome of varied etiologically related AKI patients. In recent years, the role
      of CRP is gradually recognized as an active participant in the pathogenesis and
      progression of AKI by exacerbating local inflammation, impairing the
      proliferation of damaged tubular epithelial cells and promoting fibrosis of
      injured renal tissue.

PMID- 30298657
TI  - Perspectives on acute kidney injury strategy in China.
AB  - Acute kidney injury (AKI) has imposed a heavy disease burden in China, with
      substantial underdiagnosis and undertreatment. The incidence, cause and outcome
      of patients with AKI vary according to different geographic regions and economic
      development status; therefore, regional improvement strategies are needed.
      Defining the etiology of AKI is critical in making the proper therapeutic
      regimen, and a multidisciplinary cooperative AKI team is essential in order to
      establish the early diagnosis and proper management of patients with AKI.

PMID- 30298656
TI  - Salt, water and nephron: Mechanisms of action and link to hypertension and
      chronic kidney disease.
AB  - Our knowledge on sodium and water homeostasis and regulation continues to evolve.
      A considerable amount of new information in this area has emerged in recent
      years. This review summarizes existing and new literature and discusses complex
      multi-organ effects of high-salt and low-water intake and role of arginine
      vasopressin in this process, as well as the potential clinical significance of
      non-osmotic sodium storage pool and rhythmicity of urine sodium excretion. It has
      become clear that sodium and water dysregulation can exert profound effects on
      kidney and vascular health, far greater than previously recognized. Maladaptation
      to a combined high-salt and low-water intake can be linked to the growing
      epidemic of hypertension and chronic kidney disease.

PMID- 30298658
TI  - Lupus nephritis: An update on treatments and pathogenesis.
AB  - Immunosuppressive therapies for lupus nephritis (LN) have improved significantly
      over the past few decades, resulting in growing number of choices for treatment
      individualization and improved renal and patient outcomes. Corticosteroids
      combined with mycophenolate or cyclophosphamide induces a satisfactory response
      in a high proportion of Asian and Caucasian patients, but the rate of improvement
      varies considerably between patients. Relatively low disease flare rate was
      observed in Chinese patients receiving low-dose prednisolone and mycophenolate
      maintenance. Short-term results with calcineurin inhibitors (CNI) are
      encouraging, attributed both to their immunosuppressive efficacy and the action
      of these agents on podocyte biology leading to more rapid proteinuria
      suppression. Additional data, especially on the avoidance of nephrotoxicity and
      metabolic side effects, is required to facilitate selection of patients
      appropriate for this treatment. Modifications of standard regimens such as
      reducing corticosteroid exposure or using enteric-coated mycophenolate might help
      reduce treatment-related toxicities without compromising efficacy. While clinical
      outcomes of patients have improved with recent therapeutic advances, individual
      and ethnic variations in disease manifestations and treatment response, as well
      as the prevention of infections and long-term complications still present
      challenges to frontline clinicians. Recent data from histological examination and
      translational studies also suggest that complement activation via the alternative
      pathway, immune deposition on renal tubular basement membrane, and local
      inflammatory responses involving resident kidney cells are of pathogenic
      relevance in LN. The progress of clinical and translational studies has improved
      not only the understanding of disease mechanisms but also clinical decision
      making in the management of LN.

PMID- 30298659
TI  - Taiwan renal care system: A learning health-care system.
AB  - Taiwan renal care system is an evolving learning health-care system. There are
      four facets of this system. From the early history of dialysis and Taiwan Renal
      Registry Data System, it facilitates the generation of data to knowledge.
      National multidisciplinary pre-end-stage renal disease care project and outcome
      enhances knowledge to practice. Early chronic kidney disease (CKD) programs and
      2015 Taiwan CKD clinical guidelines implicate the practice to customer, and then
      explore the causes of CKD help to resume customer to data. A learning health-care
      system allows better and safer care at lower cost, enhancement of public health
      and patient empowerment. The successful development of a learning health-care
      system was to collect, accumulate and analyze data, interpret results, deliver
      tailored message and take action to change practice. Through the established
      database and data analysis, an integrated care system would be able to improve
      clinical outcomes and achieve the most cost-effectiveness care. Acute kidney
      injury, CKD with unknown origin, palliative care and kidney transplant are our
      new focuses to struggle.

PMID- 30298660
TI  - How to treat patients with chronic kidney disease: With special focus on IgA
      nephropathy.
AB  - Chronic kidney disease has become a worldwide problem. Among chronic kidney
      disease patients, IgA nephropathy is common in the world. Serum levels of
      galactose deficient (Gd)-IgA1 and Gd-IgA1-specific antibodies are elevated in
      most IgA nephropathy patients. Glomerular Gd-IgA1 deposition has been observed by
      immunofluorescence. There are many reports that the anti-proteinuric effect is
      significantly greater in groups who receive tonsillectomy with steroid pulse
      therapy in IgA nephropathy patients. Furthermore, patients with tonsillectomy
      with steroid pulse therapy have shown a strong down-regulation of delta serum
      IgA/C3 per year and have conserved their renal function. New treatments, that is,
      Atacicept and glucocorticoid budesonide, have been developed for this disease.

PMID- 30298661
TI  - Update on treatment of immunoglobulin A nephropathy.
AB  - Immunoglobulin A nephropathy (IgAN) is the most common form of primary
      glomerulonephritis worldwide and the most common cause of end-stage renal disease
      in young adults. However, there are still no specific therapies capable of
      targeting key pathways involved in disease pathogenesis. Recently, many large
      randomized controlled trials have been reported, such as Supportive Versus
      Immunosuppressive Therapy for the Treatment of Progressive IgA Nephropathy,
      Targeted-release Budesonide Versus Placebo in Patients with IgA Nephropathy and
      Therapeutic Evaluation of Steroids in IgA Nephropathy Global, which are
      considered to update the 2012 Kidney Disease: Improving Global Outcomes
      Guideline. More importantly, with a deeper understanding of the roles of mucosal
      immunity, B-cell activation and complement activation in IgAN, the studies of
      targeting pathogenic pathways are ongoing. In this review, by systemically
      searching the clinical trials in IgAN on ClinicalTrials.gov
      (https://clinicaltrials.gov/), we update the evidence for
      corticosteroids/immunosuppressive therapy in IgAN and explore the promising
      targeting pathogenic pathway therapeutic options. With better understanding of
      pathogenesis of IgAN, emerging therapies will soon become a reality in future.

PMID- 30298662
TI  - Chronic kidney disease epidemic: How do we deal with it?
AB  - Chronic kidney disease (CKD) is a leading cause of mortality and morbidity around
      the world. The prevalence of CKD increases steadily over the past decade in
      parallel to the rapid expansion of diabetic population. Apart from increased
      mortality, CKD also has significant impact on quality of life and the economy.
      The approach to deal with the global CKD epidemic is multifaceted. Early
      detection by screening high-risk individuals such as those with hypertension and
      diabetes is important and cost-effective. However, low CKD awareness in many
      countries may impose barriers to early intervention. Hence raising CKD awareness
      among public and policy makers should be encouraged. In addition, the use of
      peritoneal dialysis, a less costly and home-based dialysis modality compared with
      in-center haemodialysis, should be promoted to maximize access to dialysis with
      limited resources. Finally, ongoing research and clinical trials through
      international collaborations could provide further insight into the
      pathophysiology of CKD progression, and establish the foundation for development
      of specific therapeutic agents to retard progression to end stage renal failure.

PMID- 30298663
TI  - Mineral bone disorders in chronic kidney disease.
AB  - As the GFR loss aggravates, the disturbed mineral metabolism worsens the bone
      microstructure and remodelling - scenario, which is known as CKD-mineral bone
      disease (MBD). CKD-MBD is characterized by : (i) abnormal metabolism of calcium,
      phosphorus, parathyroid hormone (PTH), or vitamin D; (ii) abnormalities in bone
      turnover, mineralization, volume linear growth or strength; (iii) soft-tissue
      calcifications, either vascular or extra-osseous. Uremic vascular calcification
      and osteoporosis are the most common complications related to CKD-MBD.
      Disregulated bone turnover by uremic toxin or secondary hyperparathyroidism
      disturbed bone mineralization and makes it difficult for calcium and inorganic
      phosphate to enter into bone, resulting in increased serum calcium and inorganic
      phosphate. Vascular calcification worsens by hyperphosphatemia and systemic
      inflammation. Since vitamin D deficiency plays an important role in renal
      osteodystrophy, supplement of nutritional vitamin D is important in treating
      uremic osteoporosis and vascular calcification at the same time. Its pleotropic
      effect improves the bone remodeling initiated by osteoblast and alleviates the
      risk factors for vascular calcification with less hypercalcemia than vitamin D
      receptor analogs. Therefore, nutritional vitamin D should be considered in
      managing CKDMBD.

PMID- 30298664
TI  - CKD prevention: Perspectives in Hong Kong.
AB  - Hong Kong experiences a progressive rise in the prevalence of treated end-stage
      renal disease (ESRD) as recorded by the Hong Kong Renal Registry managed by the
      Hospital Authority (HA) that takes care of 90 - 95% of the ESRD burden. The CKD
      burden is envisaged to be high, as reflected by 2 initiatives - SHARE which
      detected a high prevalence of urine or blood pressure abnormalities among 1,201
      asymptomatic individuals who underwent screening, and RISKS that aimed to further
      characterize the spread of CKD in the asymptomatic population. For CKD
      prevention, two statutory bodies - the HA and Hong Kong College of Physicians
      (HKCP), and two non-governmental organizations - Hong Kong Society of Nephrology
      (HKSN) and Hong Kong Kidney Foundation (HKKF), all have a role to play. The
      Central Renal Committee (CRC) operated under HA co-produces with HKCP and HKSN a
      clinical practice guideline for the provision of renal service in Hong Kong which
      includes CKD care and prevention. HKSN now holds annual educational symposia and
      a Continuous Medical Education (CME) course in partnership with the HKCP and
      Asian Pacific Society of Nephrology in addition to its Annual Scientific Meeting.
      The HKSN also provides a collective International Society of Nephrology (ISN)
      membership for all its full members to enhance education and other pertinent
      initiatives. For public education, the HKSN and HKKF participate in the annual
      World Kidney Day event and organize free blood pressure and CKD surveys in public
      housing estates to increase public awareness of CKD. The latter is also effected
      via regular promotion through the mass media.

PMID- 30298665
TI  - Genetic study of immunoglobulin A nephropathy: From research to clinical
      application.
AB  - Immunoglobulin A nephropathy (IgAN) is one of the most common primary
      glomerulonephritis throughout the world and a major cause of end-stage renal
      disease among East Asian population. It is widely considered that genetic factors
      play an important role in the pathogenesis of IgAN. The genetic studies of IgAN,
      is from the association studies of candidate genes and family-based designs, to
      the genome-wide association studies. Altogether there are five large genome-wide
      association studies performed, which have identified multiple susceptibility loci
      for IgAN, including several novel loci found in Chinese population. The discovery
      of these susceptibility loci has provided important insight into the potential
      biological mechanisms and pathways that influence genetic risk to IgAN. In
      addition, genetic interaction and structural variation (such as copy number
      variation) studies were also conducted to identify more variants associated with
      IgAN and disease progression. The genetic studies of IgAN have made great
      achievements in recent years. Most of susceptibility loci discovered up to date
      contain genes involved in the response to mucosal pathogens, suggesting that
      intestinal immune network for IgA production may be involved in the pathogenesis
      of IgAN. While the genetic studies of the complex diseases remain to be
      challenging, new genetic and analytical techniques and methods, especially next
      generation sequencing-based studies, need to be applied to advance the genetic
      studies of IgAN. More importantly, we need to identify the genetic factors which
      influence the clinical phenotypes and renal progression to end-stage renal
      disease. This will require the integration of genomic data with other omics
      profiles (e.g. transcriptomics, metabolomics and immunomics) in patients with
      long-term clinical follow-up data to better understand the factors underlying
      inter-individual variability, not only in disease susceptibility, but also in the
      long-term prognosis and healthcare requirements.

PMID- 30298666
TI  - Diet, gut microbiome and indoxyl sulphate in chronic kidney disease patients.
AB  - Emerging evidence suggests that intestinal dysbiosis plays an important role in
      host inflammation locally and systemically. Such pathological condition is even
      more prevailing in patients with chronic kidney disease (CKD). Of note, indoxyl
      sulphate (IS), a gut-derived uremic toxin, is notorious for its pro-inflammatory
      feature in CKD patients. IS accumulates in the body as the urinary excretion of
      uremic toxins is impaired, and further worsens the kidney function in a vicious
      cycle to CKD. Dietary restriction in vegetables, fruits and yogurt leads to the
      predominance of indole-producing intestinal microbial flora and further
      exaggerates the accumulation of IS in CKD patients. Recently, interventional
      studies have shown that circulating IS can be reduced by dietary prebiotic and/or
      probiotic supplements. However, further randomized controlled trials are
      warranted to examine whether such beneficial effect of dietary
      prebiotic/probiotic supplements could be extrapolated to better hard outcomes in
      CKD population. In this review, we would also like to emphasize the importance of
      achieving sufficient intake of dietary fibre by proper vegetable pre-treatment
      and accurate fruit selection, instead of directly avoiding these potassium-rich
      yet fibre-rich and base-producing foods.

PMID- 30298667
TI  - Advanced therapeutics in focal and segmental glomerulosclerosis.
AB  - Focal segmental glomerulosclerosis (FSGS) is a glomerulonephritis with podocyte
      injury. The renal prognosis of FSGS is relative poor. The overall remission rate
      of the FSGS patients with nephrotic syndrome to immunosuppressive treatments was
      reported as 47-66%, highlighting its therapeutic challenge-lacking in sufficient
      evidence-based interventions. In first-line treatment of nephrotic syndrome,
      daily oral prednisolone is a commonly used drug, whereas optimal treatment
      strategies, like indications and duration, remain controversial. Calcineurin
      inhibitor and cyclophosphamide are recommended in steroid-dependent/steroid
      resistant patients. However, the high unmet need in effective immunosuppressive
      treatments calls for the development of new therapy methods. Rituximab, a
      monoclonal antibody targeting CD20 B-cells, could increase the complete or
      partial remission rate, and decrease the relapse rate based on several previous
      studies on FSGS. In addition, the using of rituximab could potentially help the
      FSGS patients to stop the concomitant therapy include steroid and
      immunosuppressive agents. Other treatment options like adalimumab or abatacept
      also showed potential therapeutic effect, but still required larger Randomized
      Controlled Trial study to determine its efficiency and safety. Besides, expanding
      understanding of the genetic basis of FSGS is necessary to investigate new
      therapeutic agents. With the unsatisfied patients' outcome under the current
      treatments, innovation should be encouraged on the treatment strategy based on
      Kidney Disease: Improving Global Outcomes guideline and international
      collaborations are required for the potential novel immunosuppressive or
      immunomodulatory therapies.

PMID- 30298668
TI  - Role of Kruppel-like factor-2 in kidney disease.
AB  - Kruppel-like factor-2 (KLF2) is a transcription factor that plays a major role in
      the regulation of endothelial cell function. KLF2 protects against endothelial
      cell injury through its anti-inflammatory, anti-thrombotic and anti-angiogenic
      effects to maintain the normal vascular integrity. Our recent data indicate that
      KLF2 is down-regulated in glomerular endothelial cells of patients with diabetic
      kidney disease and that endothelial cell-specific reduction in KLF2 expression in
      experimental model of diabetic kidney disease exacerbates glomerular endothelial
      cell injury and accelerates the disease progression. KLF2 is a key
      transcriptional regulator of endothelial nitric oxide synthase, and its
      renoprotective function may be mediated through the increased endothelial nitric
      oxide synthase expression. As KLF2 expression is stimulated by shear stress, we
      also investigated the role of KLF2 in the nephrectomy mouse model, in which the
      endothelial KLF2 expression would be increased through glomerular hyperfiltration
      in the remnant kidney. Reduction of endothelial KLF2 led to increased glomerular
      endothelial cell injury and progressive kidney disease in uninephrectomized mice.
      Interestingly, KLF2 expression is also reduced in nephrectomy patients with
      progressive kidney disease as compared to those with the non-progressive disease.
      Together, these studies indicate a critical role of KLF2 in maintaining normal
      glomerular endothelial cell function and that deficiency of KLF2 leads to more
      progressive kidney disease.

PMID- 30298669
TI  - Role of renin-angiotensin system in acute kidney injury-chronic kidney disease
      transition.
AB  - Acute kidney injury (AKI) can increase the risk of developing incident chronic
      kidney disease (CKD). The severity, frequency and duration of AKI are crucial
      predictors of poor renal outcome. A repair process after AKI can be adaptive and
      kidney recovers completely after a mild injury. However, severe injury will lead
      to a maladaptive repair, which frequently progresses to nephron loss, vascular
      rarefaction, chronic inflammation and fibrosis. Although different mechanisms
      underlying AKI-CKD transition have been extensively discussed, no definite
      intervention has been proved effective to block or to retard the transition until
      recently. In CKD, renin-angiotensin system (RAS) inhibitor has been proved
      effective to slow down disease progression. Furthermore, RAS needs to be
      highlighted again in AKI-CKD transition because recent animal studies have shown
      the activation of intra-renal RAS after AKI, and RAS blockade can reduce the
      ensuing CKD and mortality. In patients with the complete renal recovery after
      AKI, administration of RAS inhibitor is associated with reduced risk of
      subsequent CKD as well. In this article, we will demonstrate the role of RAS in
      AKI-CKD transition comprehensively. We will then emphasize the promising effect
      of RAS inhibitor on CKD prevention in patients recovering from AKI based on
      evidence from the bench to clinical research. All of these discussions will
      contribute to the establishment of reliable monitoring and therapeutic strategies
      for patients with functional recovery from AKI who can be most easily ignored.

PMID- 30298670
TI  - Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa,
      age-related macular degeneration, glaucoma and cataract.
AB  - PURPOSE: To analyse intraocular cytokine levels and prevalence of intraocular
      antiretinal antibodies (ARAs) in patients with retinitis pigmentosa (RP), age
      related macular degeneration (AMD), glaucoma and cataract, and correlate the
      results to clinical manifestations. METHODS: We collected intraocular fluid
      samples from patients with RP (n = 25), AMD (n = 12), glaucoma (n = 28) and
      cataract (n = 22), and serum samples paired with the intraocular fluids from
      patients with RP (N = 7) and cataract (n = 10). Interleukin (IL)-1beta, IL-1ra,
      IL-2, IL-6, IL-6ralpha, IL-7, IL-8, IL-10, IL-17A, IL-23, thymus- and activation
      regulated chemokine (TARC), monocyte chemoattractant protein-1 (MCP-1), tumour
      necrosis factor-alpha (TNF-alpha), placental growth factor (PlGF) and vascular
      endothelial growth factor (VEGF) were measured using a multiplex assay.
      Antiretinal antibodies (ARA) detection was performed by indirect
      immunofluorescence. RESULTS: Increasing age was associated with increasing levels
      of IL-6, IL-8, TNF-alpha and VEGF. All patient groups exhibited distinct profiles
      of intraocular cytokines. Intraocular levels of IL-8 were highest in patients
      with AMD and glaucoma. Cataract patients exhibited high intraocular levels of IL
      23. Intraocular levels of IL-2, IL-6, MCP-1 and PlGF in RP patients exceeded the
      levels of serum, indicating intraocular production. Intraocular ARAs were found
      in only one patient with AMD. CONCLUSION: Increased levels of inflammatory
      cytokines in intraocular fluid of patients with originally noninflammatory ocular
      diseases show that intraocular inflammation is involved in their pathogenesis of
      these entities. Moreover, we show that increasing age is associated with
      increasing levels of intraocular cytokines and conclude that future studies on
      intraocular mediators should be corrected for age of patients.

PMID- 30298671
TI  - Optimal sample size planning for the Wilcoxon-Mann-Whitney test.
AB  - There are many different proposed procedures for sample size planning for the
      Wilcoxon-Mann-Whitney test at given type-I and type-II error rates alpha and
      beta, respectively. Most methods assume very specific models or types of data to
      simplify calculations (eg, ordered categorical or metric data, location shift
      alternatives, etc). We present a unified approach that covers metric data with
      and without ties, count data, ordered categorical data, and even dichotomous
      data. For that, we calculate the unknown theoretical quantities such as the
      variances under the null and relevant alternative hypothesis by considering the
      following "synthetic data" approach. We evaluate data whose empirical
      distribution functions match the theoretical distribution functions involved in
      the computations of the unknown theoretical quantities. Then, well-known
      relations for the ranks of the data are used for the calculations. In addition to
      computing the necessary sample size N for a fixed allocation proportion t = n1
      /N, where n1 is the sample size in the first group and N = n1  + n2 is the total
      sample size, we provide an interval for the optimal allocation rate t, which
      minimizes the total sample size N. It turns out that, for certain distributions,
      a balanced design is optimal. We give a characterization of such distributions.
      Furthermore, we show that the optimal choice of t depends on the ratio of the two
      variances, which determine the variance of the Wilcoxon-Mann-Whitney statistic
      under the alternative. This is different from an optimal sample size allocation
      in case of the normal distribution model.

PMID- 30298673
TI  - Impact of antioxidant treatment on DNA fragmentation index: a double-blind
      placebo-controlled randomized trial.
AB  - BACKGROUND: Previous reports on effect of antioxidants on sperm DNA integrity
      were equivocal, and there is a lack of randomized, placebo-controlled studies.
      OBJECTIVES: To evaluate the efficacy of combined antioxidant treatment in
      subfertile men with normal reproductive hormone levels and high sperm DNA
      fragmentation index (DFI). MATERIALS AND METHODS: This placebo-controlled, double
      blind, randomized study evaluated the effects of combined antioxidant treatment
      in 77 men from infertile couples, with normal testosterone, LH and FSH levels and
      DFI >=25%. All participants were randomly assigned to receive combined
      antioxidant treatment (vitamins, antioxidants and oligoelements) or placebo for
      six months. The primary outcome measured was DFI. Secondary outcomes were
      standard semen parameters. DFI and other semen parameters were, at each time
      point (pre-treatment, and after three and six months of treatment), compared
      between the treatment and the placebo group using Mann-Whitney U-test. RESULTS:
      Antioxidant group had higher sperm concentration after three months of treatment
      (median: 24.4 * 106 /mL vs. 27.2 * 106 /mL; P = 0.028) and borderline
      statistically significant higher concentration after six months of treatment
      (median: 24.4 * 106 /mL vs. 33.3 * 106 /mL; P = 0.053) compared to pre-treatment
      values. The DFI did not change during the 6 months of antioxidant therapy. No
      statistically significant difference between the antioxidant and placebo group
      was seen for any of the semen parameters including sperm DFI at any of the three
      time points. DISCUSSION: The increase in sperm concentration was more pronounced
      in the antioxidant treated group but not statistically significantly higher than
      among controls, perhaps due to insufficient statistical power. Previous studies
      have shown positive effect of antioxidant treatment on DFI and other semen
      parameters. However, our findings indicate that men with normal reproductive
      hormone levels may not be the primary target group for such therapy. CONCLUSION:
      Six months treatment with antioxidants had no effect on sperm DFI.

PMID- 30298672
TI  - Dual Use of Department of Veterans Affairs and Medicare Benefits on High-Risk
      Opioid Prescriptions in Veterans Aged 65 Years and Older: Insights from the VA
      Musculoskeletal Disorders Cohort.
AB  - OBJECTIVE: To examine the association of dual use of both Veterans Health
      Administration (VHA) and Medicare benefits with high-risk opioid prescriptions
      among Veterans aged 65 years and older with a musculoskeletal disorder diagnosis.
      DATA SOURCES/STUDY SETTING: Data were obtained from the VA Musculoskeletal
      Disorder (MSD) cohort and national Medicare claims data from 2008 to 2010. STUDY
      DESIGN: We conducted a retrospective analysis of Veterans enrolled in Medicare to
      examine the association of dual use with long-term opioid use (>90 days of
      prescription opioids/year) and overlapping opioid prescriptions. Multivariable
      logistic regression was performed adjusting for demographic and clinical
      characteristics. DATA COLLECTION/EXTRACTION METHODS: We identified 21,111
      Veterans enrolled in Medicare who entered the MSD cohort in 2008 and received an
      opioid prescription in 2010. We linked VHA data with Medicare claims data to
      identify opioid prescriptions for these Veterans in 2010. PRINCIPAL FINDINGS: As
      compared to Veterans who used only VHA or Medicare, Veterans with dual use of VHA
      and Medicare were significantly more likely to be prescribed long-term opioid
      therapy (OR = 4.61 (95 percent CI 4.05-5.25) and were also found to have higher
      median number of opioid prescriptions and higher odds of overlapping opioid
      prescriptions in 1 year. Patients reporting moderate-to-severe pain, non-white
      race/ethnicity, and higher scoring on the Charlson comorbidity index had
      significantly higher odds of long-term opioid prescriptions. CONCLUSIONS: Among
      Veterans aged 65 years or older, dual use of both VHA and Medicare was associated
      with higher odds of long-term opioid therapy. Our findings suggest there may be
      benefit to combining VHA and non-VHA electronic health record data to minimize
      exposure to high-risk opioid prescribing.

PMID- 30298674
TI  - A Novel Approach to Improve Repair Bond Strength of Repaired Acrylic Resin: An in
      Vitro Study on the Shear Bond Strength.
AB  - PURPOSE: To evaluate the combined effect of mechanical surface treatment with
      intermediate bonding agents (methyl methacrylate [MMA] and silane coupling
      agents) and ZrO2 nanoparticle (nano-ZrO2 ) addition to repair material on the
      shear bond strength (SBS) of repaired denture bases. MATERIALS AND METHODS: Heat
      polymerized acrylic resin was used to fabricate 130 cylindrical blocks (15 mm *
      10 mm) and divided into a control group without treatment (C, n = 10), and 3
      repair groups (n = 40/group) divided into specimens treated with alumina blasting
      alone (AB), specimens blasted with alumina combined with silane coupling agent
      (AB + SCA), or combined with MMA-based composite bonding agent (AB + MA). Treated
      groups were further subdivided according to nano-ZrO2 concentrations into 0 wt%,
      2.5 wt%, 5 wt%, and 7.5 wt% added to repair resin powder. Repair resin monomer
      and polymer were combined and packed on the repair area and then placed in a
      pressure pot at 37 degrees C for 15 minutes for polymerization. Shear bond test
      was performed using a universal testing machine. Scanning electron microscopy
      (SEM) was used to examine the effect of surface modifications on repair surfaces
      and to evaluate the topography of fracture surfaces. Tukey-Kramer multiple
      comparison test was used to detect significant differences between groups (p <=
      0.05). RESULTS: SBS (MPa) of specimens treated with alumina blasting and
      application of intermediate agents were significantly higher than the control
      group (p < 0.05), while no significant differences were found between AB and
      control group (p > 0.05). Nano-ZrO2 addition significantly increased SBS except
      for AB, and 5%, 7.5% MA (p > 0.05). SEM evaluation showed that alumina blasting
      created rougher and more porous surfaces, while SCA and MA reduced the
      irregularities and fissures. CONCLUSION: Application of bonding agents to repair
      surfaces after alumina blasting improved the repair bond strength and proved to
      be a possible new adhesive method for denture repair. Moreover, nano-ZrO2
      addition in combination with surface treatment improved the repair bond strength.

PMID- 30298676
TI  - Noise concerns of residents living in close proximity to hydraulic fracturing
      sites in Southwest Pennsylvania.
AB  - OBJECTIVE: Noise associated with nontraditional gas industry (NTGI) sites (e.g.,
      hydraulic fracturing well pads, compressor stations, processing plants) may
      create disturbances and anxiety in rural populations. This study evaluated levels
      of concern among residents of Southwestern Pennsylvania residing near NTGI sites.
      DESIGN: Noise measurements were collected inside and outside residences, and
      surveys were administered to residents. RESULTS: Daytime instantaneous sound
      levels ranged between 45.0 and 61.0 dBA. Dosimeter studies recorded day-night
      levels (Ldn ) of 53.5-69.4 dBA outside and 37.5-50.1 dBA inside, exceeding United
      States Environmental Protection Agency guidelines. Respondents indicated the NTGI
      noise disturbed their sleep, and the majority of respondents (96%) reported being
      worried about their overall health as a result of the noise. CONCLUSIONS: Health
      care professionals serving rural areas impacted by hydraulic fracturing
      (fracking) should be aware of potential noise stressors on the populations they
      serve.

PMID- 30298677
TI  - Strategic ignorance and global governance: an ecumenical approach to
      epistemologies of global power.
AB  - How can we account for the role of ignorance and knowledge in global governance?
      It is a contention of earlier scholarship in international relations and
      political sociology that knowledge production is tightly coupled with rational
      action - regardless of whether knowledge widely influences different stakeholders
      or not. This scholarship equally tends to assume an ignorance-knowledge binary
      relationship that associates ignorance with powerlessness and knowledge with
      power. This is a view we dispute. Calling for a new approach to the study of
      ignorance and knowledge in international politics, our article builds on research
      from ignorance studies, science and technology studies and critical race theory
      to derive a novel typology of epistemologies of power in which truth and
      ignorance are defined and combined in a plurality of ways. Approaching differing
      epistemologies of power in the transnational realm in a general or 'ecumenical'
      manner, we identify weaknesses in earlier approaches to the study of knowledge
      production in global affairs, and present four new concepts: 'factual
      determinism', 'cynical realism', 'unseeing proceduralism' and 'hopeful
      constructivism'. Through this framework, our article calls for greater
      recognition of the constitutive role that ignorance plays in operations of power
      on a global scale.

PMID- 30298675
TI  - Effect of maternal or post-weaning methyl donor supplementation on growth
      performance, carcass traits, and meat quality of pig offspring.
AB  - BACKGROUND: Limited studies have examined links between maternal methyl donor
      (MET) supplementation and the growth-development characteristics of offspring,
      and possible underlying mechanisms for such links. This study investigated the
      effect of maternal or post-weaning MET-supplementation on growth performance,
      carcass characteristics, and meat quality of the finishing (d 180) offspring.
      Twenty-four sows were placed on a control (C) or MET-supplemented diet during
      pregnancy and lactation. Forty-eight female offspring were fed the control or MET
      supplemented diet from weaning to 6 months of age, resulting in four study groups
      (six litters per group): C/C, C/MET, MET/C, and MET/MET. RESULTS: Maternal MET
      supplementation increased average daily gain (ADG), body weight (BW), lean
      percentage and longissimus dorsi (LD) of the offspring at day 180 (P < 0.05), and
      upregulated the myosin heavy chain IIx, myogenic differentiation and muscle
      regulatory factor 4 mRNA levels in the LD muscle (P < 0.05). Meanwhile, offspring
      from maternal MET-supplementation exhibited a higher pH24h post mortem and
      superoxide dismutase activity, a lower L* 45min , glycolytic potential,
      malonaldehyde content in the LD muscle, and plasma homocysteine concentration (P
      < 0.05). CONCLUSION: Maternal MET-supplementation has a remarkable effect on
      growth performance, carcass traits, and meat quality of the offspring, which is
      associated with increased expression levels of myogenic genes and anti-oxidant
      capacity. (c) 2018 Society of Chemical Industry.

PMID- 30298678
TI  - Epstein-Barr virus associated smooth muscle tumors in solid organ transplant
      recipients: Incidence over 31 years at a single institution and review of the
      literature.
AB  - INTRODUCTION: Epstein-Barr virus (EBV) associated smooth muscle tumors (EBV-SMT)
      are a rare complication of solid organ transplantation (SOT). Incidence data
      related to this EBV-SMT are limited. EBV DNA is universally present in these
      tumors. How these cells get infected with EBV, whether this is a result of
      primary EBV infection vs reactivation, and how persistent active EBV infection
      post-transplant influences EBV-SMT pathogenesis remains unknown. METHODS: Among
      5006 SOT recipients (474 pediatric, 4532 adult) receiving SOT at our center
      between Jan 1984 and Dec 2015, three cases of post-transplant EBV-SMT were
      identified. RESULTS: All cases were pediatric heart transplants who were EBV
      seronegative prior to transplant, and experienced primary EBV infection with
      persistently elevated EBV viral loads, despite antiviral therapy. Two are
      deceased at 3.2 and 0.9 years post-diagnosis, while one remains alive 6.2 years
      post diagnosis. The overall local incidence of post-transplant EBV-SMT at our
      institution was 0.7 (95% CI, 0.2-1.7) per 1000 patient years, and 2.6 (95% CI,
      0.6-6.7) per 1000 patient years in pediatric heart transplants. A literature
      review identified 36 pediatric and 51 adult cases of post-transplant EBV-SMT.
      CONCLUSIONS: We hypothesize that pre-transplant EBV seronegativity, followed by
      primary EBV infection and persistently high EBV viral loads, represents a unique
      risk factor for post-transplant EBV-SMT. Pediatric heart transplant recipients
      were found to be disproportionately affected by post-transplant EBV-SMT at our
      institution.

PMID- 30298679
TI  - Assessment of oral health status of children with epilepsy: A retrospective
      cohort study.
AB  - BACKGROUND: Epileptic children are liable to experience oral health problems
      either due to the disease itself or medications administered to control the
      condition. AIM: We aimed to investigate caries experience, gingival health and
      oro-facial traumatic injuries in a sample of epileptic Egyptian children. DESIGN:
      A retrospective cohort study was conducted from September 2016 to April 2017
      using data from medical records in Children Hospital at Ain Shams University.
      Dental examination was performed for 100 epileptic children and 80 healthy
      subjects who matched in age, gender, and socio-economic status. Caries experience
      was measured using the decayed, missing and filled teeth (DMFT or dmft) index and
      gingival index (GI) of Loe and Sillness was used to determine gingival health
      status. Oro-facial injuries were assessed using the WHO classification of trauma.
      Quantitative data were presented as mean, SD, and 95% CI values. Qualitative data
      were presented as frequencies and percentages and the significance level was set
      at P <= 0.05. RESULTS: The mean +/- SD GI for epileptic children was
      significantly higher (1.16 +/- 0.42) than that of healthy children. (1.01 +/-
      0.11) Healthy subjects had significantly lower mean dmf index scores 2.2 +/- 2.6
      compared to epileptic subjects where mean dmf scores were 4.1 +/- 2.1. No
      significant difference, however, was detected between the two groups regarding
      caries experience in permanent dentition or incidence of oro-facial injuries.
      CONCLUSIONS: Epileptic children are highly burdened with gingival problems and
      liable to develop dental caries especially in primary dentition. Oral traumatic
      injuries, however, are not common complications if seizure attacks are well
      controlled.

PMID- 30298680
TI  - Lipid and color stability of the meat and sausages of broiler fed with calcium
      anacardate.
AB  - BACKGROUND: Anacardic acid, a phenolic compound, represents 90% of cashew nut
      shell liquid, which is a byproduct from the industrial processing of cashew nuts.
      This study aimed to add calcium anacardate (CA) to broilers' diets as a source of
      anacardic acid, to evaluate its antioxidant effect in breast meat and in
      processed meat products (sausages). For this purpose, birds were fed according to
      the following treatments: diet without antioxidant and diets containing 2.5, 5.0,
      7.5, or 10.0 g kg-1 CA. Chicken breast meat was stored frozen for 90 days. The
      thigh and drumsticks were used to produce chicken sausages that were kept in
      refrigerated conditions for 90 days. Lipid oxidation and color stability were
      assessed every 30 days. RESULTS: For breast meat, a 2.5 g kg-1 concentration of
      CA was insufficient to retard lipid oxidation, whereas 10.0 g kg-1 gave rise to a
      pro-oxidant effect and 5.0 g kg-1 slowed the oxidation up to 50 days. A level of
      7.5 g kg-1 of CA was effective in retarding oxidation, favoring colour stability
      during the 90-days frozen storage. For sausages, 2.5 g kg-1 of calcium anacardate
      in broiler diets was sufficient to retard lipid oxidation. Calcium anacardate 7.5
      g kg-1 provided greater redness in the sausages compared with the control and
      with the other treatments containing 5.0 and 10.0 g kg-1 . CONCLUSIONS: Calcium
      anacardate is a potential natural antioxidant for breast meat and sausages in
      storage when added to broilers' diets. (c) 2018 Society of Chemical Industry.

PMID- 30298681
TI  - Effects of dietary supplemental methionine source and betaine replacement on the
      growth performance and activity of mitochondrial respiratory chain enzymes in
      normal and heat-stressed broiler chickens.
AB  - This study aimed to evaluate the effects of dietary supplemental methionine (Met)
      source and betaine (Bet) replacement for Met on performance and activity of
      mitochondrial respiratory chain enzymes (MRCEs) in normal and heat-stressed
      broiler chickens. Total of 1,200-day-old Ross 308 chicks were allocated to two
      houses, each consisted of 12 treatments, five replicates of 10 birds each with 2
      * 2*3 * 2 (temperature * Met source * Met level * Bet, respectively) split-plot
      factorial arrangement. Met level in the basal diets was 70% requirements (Req)
      that was increased to the requirement or 130% by supplemental dl- or l-Met. Bet
      was or was not substituted at the rate of 30% supplemental dl- or l-Met. Feed
      conversion ratio (FCR) in chicks fed 70% l-Met was lower than those fed 70% dl
      Met diet during 1-10 days (p = 0.04). Broilers fed diets containing requirement
      or 130% Met, regardless of its source, showed higher weight gain (WG) than those
      received 70% Met diet during 11-42 days (p < 0.001). Feed intake (FI) of broilers
      fed 130% Met diet was decreased compared to other two groups during 11-42 days (p
      < 0.05). One hundred thirty percent Met requirement diet resulted in lower FCR
      comparing to other two groups during 11-42 days (p < 0.001). Heat-stressed birds
      grew less than those under normal condition (p < 0.05). Broilers fed Req Met diet
      under normal temperature exhibited higher activities of complexes (Cox) I and III
      (p < 0.05). Cox I activity in heat-stressed birds fed Bet + diet was similar to
      those fed Bet-diet under normal temperature (p = 0.046). It is concluded that
      performance and the activities of Cox I and III were increased as the level of
      Met increased. Bet replacement for 30% supplemental Met resulted in similar
      consequences comparing to non-Bet replacement diets on performance, but increased
      the activity of Cox III. l-Met was effective than dl-Met at the cellular level.
      High ambient temperature depressed performance and MRCE activity.

PMID- 30298682
TI  - Characterisation of the in vivo interactions between detomidine and methadone in
      horses: Pharmacokinetic and pharmacodynamic modelling.
AB  - BACKGROUND: Pharmacokinetic (PK)/pharmacodynamic (PD) modelling offers new
      insights to design protocols for sedation and analgesia in standing horses.
      OBJECTIVES: To evaluate the parameters and interactions between detomidine and
      methadone when given alone or combined in standing horses. STUDY DESIGN:
      Randomised, placebo-controlled, blinded, crossover. METHODS: Eight adult healthy
      horses were given six treatments intravenously: saline (SAL); detomidine (5
      MUg/kg bwt; DET); methadone (0.2 mg/kg bwt; MET) alone or combined with
      detomidine (2.5 [MLD], 5 [MMD] or 10 [MHD] MUg/kg bwt). Venous blood samples were
      obtained at predetermined times between 0 and 360 min after drug administration.
      Plasma detomidine and methadone were measured using a single, liquid/liquid
      extraction technique by liquid chromatography coupled with a triple quadrupole
      mass spectrometer (LC-MS/MS). Sequential PK/PD modelling compared rival models,
      with and without PK and PD interaction between drugs, to fit the PD data
      including height of the head above the ground (HHAG), a visual analogue scale for
      sedation (VAS), electrical (ET), thermal (TT) and mechanical (MT) nociceptive
      thresholds and gastrointestinal motility (GIM) . RESULTS: Two and three
      compartment models best described the PK of detomidine and methadone,
      respectively. Detomidine decreased its own clearance as well as the clearance of
      methadone. The interaction of methadone on the effect of detomidine revealed an
      infra-additive (partial antagonism) effect for HHAG (alpha = -1.33), VAS (alpha =
      -0.98) and GIM (alpha = -1.05), a positive potentiation for ET (pot = 0.0041) and
      TT (pot = 0.133) and a synergistic to additive effect for MT (alpha = 0.78). MAIN
      LIMITATIONS: This is a small experimental study. CONCLUSIONS: Different PK/PD
      interactions were demonstrated for each PD parameter and could be modelled in
      vivo. The modelling of our data will allow us to simulate and predict the effect
      of constant rate infusions of both drugs for future investigations.

PMID- 30298684
TI  - Bioprosthetic aortic valve leaflet disruption with high energy electrocautery to
      prevent coronary artery obstruction during valve-in-valve transcatheter aortic
      valve replacement.
AB  - Transcatheter aortic valve replacement (TAVR) is well-established for the
      treatment of bioprosthetic aortic valve stenosis (AS) in high surgical risk
      patients. Coronary artery obstruction from displacement of the bioprosthetic
      valve leaflets during valve-in-valve (VIV) TAVR is a rare, but potentially fatal,
      complication. Recently, the bioprosthetic aortic scallop intentional laceration
      to prevent iatrogenic coronary artery obstruction (BASILICA) procedure was
      developed as a method for disrupting bioprosthetic leaflets in patients
      undergoing VIV TAVR at high risk for coronary obstruction. This case describes a
      successful VIV TAVR utilizing a simplified concept of the BASILICA technique in a
      patient where the full procedure could not be completed.

PMID- 30298683
TI  - Characterization and development of SAPP as a specific peptidic inhibitor that
      targets Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is a keystone bacterium in the oral microbial
      communities that elicits a dysbiosis between the microbiota and the host.
      Therefore, inhibition of this organism in dental plaques has been one of the
      strategies for preventing and treating chronic periodontitis. We previously
      identified a Streptococcal ArcA derived Anti-P gingivalils Peptide (SAPP) that in
      vitro, is capable of repressing the expression of several virulence genes in the
      organism. This leads to a significant reduction in P gingivalis virulence
      potential, including its ability to colonize on the surface of Streptococcus
      gordonii, to invade human oral epithelial cells, and to produce gingipains. In
      this study, we showed that SAPP had minimal cytotoxicity to human oral
      keratinocytes and gingival fibroblasts. We observed that SAPP directly bound to
      the cell surface of P gingivalis, and that alterations in the sequence at the N
      terminus of SAPP diminished its abilities to interact with P gingivalis cells and
      repressed the expression of virulence genes. Most strikingly, we demonstrated
      using an ex-vivo assay that besides its inhibitory activity against P gingivalis
      colonization, SAPP could also reduce the levels of several other oral Gram
      negative bacteria strongly associated with periodontitis in multispecies
      biofilms. Our results provide a platform for the development of SAPP-targeted
      therapeutics against chronic periodontitis.

PMID- 30298685
TI  - In-hospital opioid consumption, but not pain intensity scores, predicts 6-month
      levels of pain catastrophizing following hepatic resection: A trajectory
      analysis.
AB  - BACKGROUND: The study aims were to model acute pain intensity and opioid
      consumption trajectories up to 72 hr after open hepatic resection, identify
      predictors of trajectory membership and examine the association between
      trajectory memberships and 6-month pain and psychological outcomes. This is a
      long-term analysis of a published randomized controlled trial on the impact of
      medial open transversus abdominis plane catheters on post-operative outcomes.
      METHODS: A total of 152 patients (89 males; mean age 63.0 [range: 54-72])
      completed questionnaires on pain and related characteristics pre-operatively and
      6 months post-operatively. Total opioid use was recorded several times over a 72
      hr period while self-reported pain intensity scores were collected multiple times
      until hospital discharge. Analyses were carried out using growth mixture
      modelling, logistic regression and general linear models. RESULTS: Both pain
      intensity and opioid consumption showed that a four-trajectory model best fits
      the data. Patients in the lowest opioid consumption trajectory were more likely
      to be classified in the constant mild pain intensity trajectory. Age and baseline
      levels of anxiety significantly predicted opioid trajectory membership while
      baseline depressive symptoms significantly predicted pain intensity trajectory
      membership. Patients in the two highest opioid consumption trajectories reported
      significantly higher levels of pain catastrophizing at 6 months compared to
      patients in the other 3 trajectories (all p < 0.05). CONCLUSION: High consumption
      of opioids after surgery is associated with higher levels of pain catastrophizing
      6 months later. Identification of patients within these trajectories may lead to
      the development of early interventions targeted to high risk individuals.
      SIGNIFICANCE: Differences in initial levels of opioid consumption and rates of
      change in opioid consumption shortly after surgery can help predict long-term
      psychological responses to pain. Identifying key characteristics associated with
      initial opioid consumption can lead to the development of cost-effective early
      interventions targeted to high risk individuals.

PMID- 30298686
TI  - A Simple Screening Tool to Predict Outcomes in Older Adults Undergoing Emergency
      General Surgery.
AB  - OBJECTIVES: To determine whether the Flemish version of the Triage Risk Screening
      Tool (fTRST) can be used to accurately assess frailty in an emergency setting.
      DESIGN: Prospective observational study. SETTING: of a tertiary referral
      hospital. PATIENTS: All individuals aged 70 and older consecutively admitted to
      the emergency surgery unit with an urgent need for abdominal surgery between
      December 2015 and May 2016 who met inclusion criteria (N=110). MEASUREMENTS:
      Individuals were screened with the fTRST and additional metrics such as the age
      adjusted Charlson Comorbidity Index and American Society of Anesthesiology score.
      Thirty- and 90-day postoperative complications where recorded. Regression
      analyses were performed to identify possible preoperative predictors of adverse
      outcomes. RESULTS: Thirty-day major complications (Clavien-Dindo Classification 3
      5) occurred in 28.2% of participants (n=31). fTRST had the highest correlation
      with major complications (odds ratio (OR) = 7.42). All participants who died
      within 30 days of surgery has a fTRST score of 2 or greater (area under the
      receiver operating curve (AUC)=71.3). When risk factors for overall 90-day
      mortality were analyzed, a fTRST score of 2 or greater had sensitivity of 96%
      (95% confidence interval CI=79.6-99.9%), specificity of 43.5% (95% CI=32.8-54.7%)
      (AUC=69.8%; OR=18.50, 95% CI=2.39-143.11, p = .005). The average length of
      hospital stay was more than twice as long in the group with a fTRST score of 2 or
      greater (15.2 days) than in those with a score less than 2 (6.6 days) (p = .005).
      CONCLUSION: The fTRST is an effective tool to predict mortality, morbidity, and
      length of stay after emergency surgery and can therefore be used to anticipate
      postoperative course, determine care goals, and plan for involvement of a
      dedicated geriatric care team.

PMID- 30298687
TI  - Normal Diffusivity of the Domestic Feline Brain.
AB  - Diffusion magnetic resonance imaging (MRI) provides useful information about
      neuroanatomy and improves detection of neuropathology. As yet a comprehensive
      evaluation of the diffusivity parameters within the feline brain has not been
      documented. In this study, we anesthetized and performed in vivo MRI on the brain
      of eight neurologically normal felines. A T1-weighted structural sequence with a
      resolution of 0.5mm3 and a parallel diffusion weighted sequence with 61
      directions and a resolution of 1.5mm3 was obtained. After correction and
      processing the diffusion brain data were parcellated into 151 regions of interest
      using previously published priors. These regions were grouped according to their
      lobar location within the brain (frontal, occipital, temporal, parietal,
      thalamus, midbrain, cerebellum and white matter). The mean and standard deviation
      of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and
      axial diffusivity (AD) for these 151 individual regions and lobar groups were
      calculated and averaged across participants, creating a comprehensive
      distribution range of diffusion tensor values. When regions were statistically
      evaluated, white matter had significantly higher FA and RD and lower AD and MD
      diffusivity parameters when compared to other regions. Additionally, thalamic
      regions had significantly higher FA values than parietal and occipital regions.
      This information will not only help inform feline neuroanatomy but will serve as
      a reference standard for future feline neuroimaging studies. This article is
      protected by copyright. All rights reserved.

PMID- 30298688
TI  - ACMHN's 44th International Mental Health Nursing Conference Mental Health is a
      Human Right 24-26 October 2018 Pullman Cairns International, Cairns, Australia.

PMID- 30298689
TI  - Antarctic heterotrophic bacterium Hymenobacter nivis P3T displays light-enhanced
      growth and expresses putative photoactive proteins.
AB  - Hymenobacter nivis P3T is a heterotrophic bacterium isolated from Antarctic red
      snow generated by algal blooms. Despite being non-photosynthetic, H. nivis was
      dominantly found in the red snow environment that is exposed to high light and UV
      irradiation, suggesting that this species can flourish under such harsh
      conditions. In order to further understand the adaptive strategies on the snow
      surface environment of Antarctica, the genome of H. nivis P3T was sequenced and
      analyzed, which identified genes putatively encoding for light-reactive proteins
      such as proteorhodopsin, phytochrome, photolyase and several copies of
      cryptochromes. Culture-based experiments revealed that H. nivis P3T growth was
      significantly enhanced under light conditions, while dark conditions had
      increased extracellular polymeric substances. Furthermore, the expression of
      several putative light-reactive proteins was determined by proteomic analysis.
      These results indicate that H. nivis P3T is able to potentially utilize light,
      which may explain its dominance on the red snow surface environment of
      Antarctica. ORIGINALITY-SIGNIFICANCE STATEMENT: The role of proteorhodopsin in
      heterotrophic bacteria is not well-characterized, as only a handful of
      proteorhodopsin-harbouring isolates were shown to have a light-enhanced phenotype
      through culture-based experiments to date. This is the first study that
      demonstrates light-stimulated growth and protein expression evidence of
      photoactive proteins for a non-marine psychrophile and for a member of the genus
      Hymenobacter. It is also the first study that provides comprehensive proteome
      information for this genus. This study presents significant results in
      understanding the adaptive mechanism of a heterotrophic non-photosynthetic
      bacterium thriving on the snow surface environment of Antarctica as well as
      demonstrating the role of light-utilization in promoting growth, possibly through
      proteorhodopsin.

PMID- 30298690
TI  - Reinforcement of variability facilitates learning in humans.
AB  - Studies with rats and pigeons showed that reinforcement of response variability
      improved learning of difficult response sequences. The results suggested that
      concurrent reinforcement of variability might be a helpful tool when educators or
      therapists attempt to teach individuals with learning difficulties. However,
      similar experiments with humans failed to confirm the results. In fact, in the
      human case, concurrent reinforcement of variability interfered with learning. The
      present experiment studied the same phenomenon with human participants in the
      context of a computer-based game. Our results were consistent with the nonhuman
      animal findings. When students in our experiment were concurrently reinforced for
      sequence variability, they were more likely than control participants to learn a
      difficult response sequence. We conclude that reinforcement of variability can
      facilitate learning-in humans as well as animals -and discuss possible reasons
      for the difference between our results and the previous human findings.

PMID- 30298691
TI  - Bioinformatic analysis reveals novel hub genes and pathways associated with
      hypertensive nephropathy.
AB  - AIM: Hypertensive nephropathy (HTN) is one of the leading causes of end-stage
      renal disease and is closely associated with inflammation and tubule-interstitial
      fibrosis. The molecular mechanism underlying HTN remains unclear. This study
      utilized bioinformatic analysis to identify the novel gene targets for HTN.
      METHODS: We downloaded the microarray data of GSE99325 and GSE32591 from Gene
      Expression Omnibus. The dataset comprised 20 HTN and 15 normal samples. The
      differentially expressed genes (DEGs) were identified, and then gene ontology
      (GO) enrichment was performed, and a GO tree was constructed by using
      clusterProfiler and ClueGO. In addition, a protein-protein interaction (PPI)
      network was established using the Search Tool for the Retrieval of Interacting
      Genes database and visualized by Cytoscape. The novel hub genes were validated in
      in vitro experiments. RESULTS: A total of 267 genes (117 up-regulated and 150
      down-regulated genes) were identified as DEGs. GO analysis and the GO tree
      indicated that the DEGs were mainly associated with steroid hormone response and
      the extracellular matrix. Basing on the PPI network, we screened out several
      novel hub genes. Considering the findings and the literature review, we focused
      on and validated the DUSP1, TIMP1, FOS, and JUN genes, which may play significant
      roles in the pathogenesis of HTN. These findings were consistent with the
      bioinformatic results for the in vitro validation. CONCLUSION: This study
      identified for the first time novel hub genes with microarray data in HTN by
      using bioinformatic analysis and provided novel evidence and clues for future
      works. This article is protected by copyright. All rights reserved.

PMID- 30298692
TI  - Prospective motion correction improves high-resolution quantitative
      susceptibility mapping at 7T.
AB  - PURPOSE: Recent literature has shown the potential of high-resolution
      quantitative susceptibility mapping (QSM) with ultra-high field MRI for imaging
      the anatomy, the vasculature, and investigating their magnetostatic properties.
      Higher spatial resolutions, however, translate to longer scans resulting,
      therefore, in higher vulnerability to, and likelihood of, subject movement. We
      propose a gradient-recalled echo sequence with prospective motion correction
      (PMC) to address such limitation. METHODS: Data from 4 subjects were acquired at
      7T. The effect of small and large motion on QSM with and without PMC was assessed
      qualitatively and quantitatively. Full brain QSM and QSM-based venograms with up
      to 0.33 mm isotropic voxel size were reconstructed. RESULTS: With PMC, motion
      artifacts in QSM and QSM-based venograms were largely eliminated, enabling-in
      both large- and small-amplitude motion regimes-accurate depiction of the cortex,
      vasculature, and other small anatomical structures that are often blurred as a
      result of head movement or indiscernible at lower image resolutions. Quantitative
      analyses demonstrated that uncorrected motion could bias regional susceptibility
      distributions, a trend that was greatly reduced with PMC. CONCLUSION:
      Qualitatively, PMC prevented image degradation because of motion artifacts,
      providing highly detailed QSM images and venograms. Quantitatively, PMC increased
      the reproducibility of susceptibility measures.

PMID- 30298693
TI  - Platelet Indices as a marker for early prediction of erectile dysfunction in
      diabetic patients.
AB  - Erectile dysfunction is one of the major concerns in diabetic patients. Platelet
      Indices including mean platelet volume, platelet count and platelet distribution
      width are important biomarkers for platelet activation and pathophysiology of
      atherothrombosis. Measurement of Platelet Indices may early predict erectile
      dysfunction in diabetic men. This study aimed to measure Platelet Indices in
      diabetic patients with erectile dysfunction and to correlate between them and
      erectile dysfunction especially of vasculogenic type. The study included 30
      diabetic patients with diagnosed erectile dysfunction and 20 normal males as a
      control. Each patient was evaluated by history, International Index of Erectile
      Function-5, general and local examination, HbA1c, pharmaco-penile duplex
      ultrasonography and blood sample to measure Platelet Indices. Platelet
      distribution width and mean platelet volume were significantly higher in patients
      than controls (p < 0.001). Their levels were significantly higher in vasculogenic
      erectile dysfunction than other types (p < 0.001). No statistically significant
      association regards the platelet count (p > 0.05). We concluded that Platelet
      Indices are high in diabetic patients with erectile dysfunction especially those
      with vasculogenic aetiology. They can predict erectile dysfunction in diabetic
      men early, and so they may be considered as cheap, available and useful biomarker
      for early diagnosis of vasculogenic erectile dysfunction in diabetic patients.

PMID- 30298694
TI  - Bladder cancer surveillance in patients with spinal cord injuries.

PMID- 30298695
TI  - Is a pillow a risk factor for glaucoma?
AB  - PURPOSE: To study whether a clinically significant increase in intraocular
      pressure (IOP) occurs during simulated sleep conditions with the subject's head
      turned comfortably into a pillow (the simulated sleep position) and the effect of
      protective glasses on any such IOP rise. METHODS: A specially developed
      electronic epipalpebral pressure (EPP) sensor was attached to an eyelid of the
      right eye of all participants: 11 patients with primary open-angle glaucoma and
      11 healthy volunteers. During calibration, mechanical pressure was applied to the
      EPP sensor taped to the lower eyelid and the IOP was measured simultaneously at
      the slit lamp by Goldmann applanation tonometry. The EPP was increased in a
      stepwise fashion to assess the relationship between EPP and IOP for each
      individual eye. Thereafter, EPP (with the sensor now taped to the upper eyelid)
      measurements were performed in the simulated sleep position, both with and
      without protective glasses. The EPP was determined in each individual eye, and
      the estimated IOP was then inferred from the established EPP/IOP relationship.
      RESULTS: In the simulated sleep position, the mean IOP increased by an estimated
      19.6 mmHg (SD: 7.5; range 11.6-32.8; p < 0.0001) in the patient group and 28.0
      mmHg (SD: 9.6; range 12.3-41.1); p < 0.0001) in the control group. When the
      subjects wore protective glasses, the mean estimated IOP decreased again by 16.3
      mmHg (SD: 5.6; range 9.8-28.1; p < 0.0001) in the patient group and 25.1 mmHg
      (SD: 8.2; range 11.7-38.3; p = <0.0001) in the control group. CONCLUSION: Turning
      the head into a pillow gave a large and clinically significant increase in the
      estimated IOP in the simulated sleep position. With protective glasses, however,
      the increase in estimated IOP was almost absent. Therefore, protective shielding
      of the eyes during sleep may be a treatment option in glaucoma.

PMID- 30298696
TI  - Biallelic mutations in PMFBP1 cause acephalic spermatozoa.
AB  - The majority of men with defects in spermatogenesis remain undiagnosed. Acephalic
      spermatozoa is one of the diseases causing primary infertility. However, the
      causes underlying over half of affected cases remain unclear. Here, we report by
      whole-exome sequencing the identification of homozygous and compound heterozygous
      truncating mutations in PMFBP1 of two unrelated individuals with acephalic
      spermatozoa. PMFBP1 was highly and specifically expressed in human and mouse
      testis. Furthermore, immunofluorescence staining in sperm from a normal control
      showed that PMFBP1 localizes to the head-flagella junction region, and the
      absence of PMFBP1 was confirmed in patients harboring PMFBP1 mutations. In
      addition, we generated Pmfbp1 knock-out (KO) mice, which we found recapitulate
      the acephalic sperm phenotype. Label-free quantitative proteomic analysis of
      testicular sperm from Pmfbp1 KO and control mice showed 124 and 35 proteins,
      respectively, increased or decreased in sperm from KO mice compared to that found
      in control mice. Gene ontology analysis indicates that the biological process of
      Golgi vesicle transport was the most highly enriched in differentially expressed
      proteins, indicating process defects related to Golgi complex function may
      disturb formation of the head-neck junction. Collectively, our data indicate that
      PMFBP1 is necessary for sperm morphology in both humans and mice, and that
      biallelic truncating mutations in PMFBP1 cause acephalic spermatozoa.

PMID- 30298697
TI  - Neonatal vitamin K deficiency in the son of a mother with short bowel syndrome.

PMID- 30298698
TI  - Stress and quality of life in parents of children with phenylketonuria.
AB  - BACKGROUND: Phenylketonuria is a hereditary disease caused by the lack or
      deficiency of phenylalanine hydroxylase enzyme activity. Parents of children with
      phenylketonuria undergo significant stress during their childcare years. They are
      also responsible for controlling their children's dietary treatment and this may
      affect their quality of life. The purpose of this study was to investigate the
      relationship between stress and quality of life in parents of children with
      phenylketonuria. METHODS: The present cross-sectional study is a correlation
      analytical research performed on parents of children with phenylketonuria in
      Kerman province in Iran in 2017. In total, 124 parents were chosen by consensus
      method. Parents completed the perceived stress scale and quality of life (SF36).
      SPSS software version 18 (https://www.presidion.com/software/ibm-spss-trial
      downloads/) was used to analyze the data. RESULTS: Total scores of stress and
      quality of life were 28.81 +/- 8.74 and 45.97 +/- 21.22. There was a significant
      negative correlation between quality of life and perceived stress (p < 0.001 and
      rho = -0.58). CONCLUSION: Parents of children with phenylketonuria have moderate
      quality of life and relatively high stress. The medical community and authorities
      should take steps to improve the quality of life and reduce stress experienced by
      parents of children with phenylketonuria.

PMID- 30298699
TI  - Ensiling characteristics, in vitro rumen fermentation, microbial communities and
      aerobic stability of low-dry matter silages produced with sweet sorghum and
      alfalfa mixtures.
AB  - BACKGROUND: Silages produced with grass and legume mixtures may have positive
      associative effects on silage quality and animal performance when ruminants are
      fed the silages. The present study aimed to determine the preservation
      characteristics, in vitro rumen fermentation profile and microbial abundance of
      silages, produced with mixtures of sweet sorghum (SS) and alfalfa (AF) in
      different ratios: 100:0 (Control), 75:25 (SA25), 50:50 (SA50), 25:75 (SA75) and
      0:100 (SA100) on a fresh weight basis. RESULTS: As the proportion of AF increased
      in the silages, pH, acetic acid, ammonia nitrogen and crude protein (CP)
      concentrations, and aerobic stability increased (P < 0.05), whereas lactic acid
      and neutral detergent fibre (NDF) and acid detergent fibre (ADF) concentrations
      decreased (P < 0.05). Increasing the proportion of AF in the silages, increased
      (P < 0.05) the in vitro degradability of dry matter and CP, as well as the
      proportions of genus Prevotella, but decreased (P < 0.05) the in vitro
      degradability of NDF (IVNDFD) and ADF (IVADFD) and proportions of Butyrivibrio
      fibrisolvens. Compared to the Control silage, SA25 silage had greater (P < 0.05)
      proportions of Fibrobacter succinogenes and Ruminococcus flavefaciens, IVNDFD,
      IVADFD, ruminal short chain fatty acids and microbial protein concentrations, as
      well as lower (P < 0.05) methane production. CONCLUSION: The silage produced with
      the SS to AF ratio of 75:25 was the most suitable for ruminants use as a result
      of the optimal balance of fermentation quality, feed-nutritional value and
      aerobic stability. (c) 2018 Society of Chemical Industry.

PMID- 30298700
TI  - Long-term clinical outcome of persistent left bundle branch block after
      transfemoral aortic valve implantation.
AB  - OBJECTIVE: The impact of persistent left bundle-branch block (pLBBB) on long-term
      clinical outcome remains to be determined. BACKGROUND: New-onset of pLBBB occurs
      frequently after transfemoral aortic valve implantation (TAVI). METHODS: Seven
      hundred and seven consecutive patients who underwent TAVI were analyzed for
      baseline and procedural characteristics and clinical outcome in an up to 2-year
      follow-up. Patients were divided into either a group with pLBBB until hospital
      discharge or a group without LBBB. We performed propensity-score matching and
      analyzed baseline characteristics, procedural data and clinical outcome of both
      groups. Patients received balloon-expandable valves in 56.4%, mechanically
      expandable valves in 37.5%, and self-expandable valves in 6.3%. RESULTS: A new
      onset, pLBBB was observed in 47.5% of patients after TAVI. The implantation of a
      mechanically expandable valve was associated with higher rate of pLBBB (54.2% vs.
      20.8%, P < 0.001), whereas implantation of a balloon-expandable valve was
      associated with lower incidence of pLBBB (39.8% vs. 73.1%, P < 0.001). Deeper
      ventricular implantation at left-coronary side led to higher rates of pLBBB (7.5
      +/- 2.5 vs. 6.7 +/- 2.6 mm, P < 0.001). The occurrence of pLBBB was associated
      with higher rates of permanent pacemaker implantation (40.9% vs. 15.9%, P <
      0.001). By multivariate analysis, implantation of a mechanically expandable valve
      (Boston Scientific Lotus valve) was identified as independent predictor of
      occurrence of pLBBB (odds ratio 4.7, confidence interval 3.2-7.0, P < 0.001). In
      the 2-year follow-up, there were no significant differences between "pLBBB" and
      "no LBBB"-groups regarding mortality and rehospitalization due to heart failure.
      CONCLUSIONS: The occurrence of pLBBB is associated with the choice of valve type
      and implantation depth and requires significantly higher rates of permanent
      pacemaker implantations. Importantly, there are no differences in the 2-year
      follow-up regarding mortality and rehospitalization due to heart failure.

PMID- 30298701
TI  - Comparison of stereotactic body radiotherapy versus metastasectomy outcomes in
      patients with pulmonary metastases.
AB  - BACKGROUND: We compared the treatment outcomes of stereotactic body radiotherapy
      (SBRT) and metastasectomy in patients with pulmonary metastases. METHODS: Twenty
      one patients received SBRT (total radiation doses 60 Gy in 3 fractions or 48 Gy
      in 4 fractions) and 30 underwent metastasectomy, most (93.3%) with wedge
      resection. The patients were followed for a median of 13.7 months. The tumor size
      in the SBRT group was larger than in the metastasectomy group (median 2.5 vs.
      1.25 cm; P = 0.015). Patients with synchronous metastases were more likely to be
      treated with SBRT than with metastasectomy (P = 0.006). RESULTS: There was no
      significant difference in the local control rates of the treatment groups (P =
      0.163). Progression-free survival (PFS) was longer in the metastasectomy than in
      the SBRT group (P = 0.02), with one and two-year PFS rates of 51.1% and 46%
      versus 23.8% and 11.9%, respectively. The one and two-year overall survival (OS)
      rates were 95% and 81.8% in the metastasectomy group and 79.5% and 68.2%, in the
      SBRT group, respectively. In multivariate analysis, synchronous metastasis was
      related to poor PFS, and tumor size was the most significant factor affecting OS.
      There were no significant differences in PFS and OS between treatment groups
      after dividing patients according to the presence or absence of synchronous
      metastases. CONCLUSIONS: SBRT is considered a suitable local modality against
      pulmonary metastases; however, patients with synchronous metastases are only
      likely to obtain a small benefit from local treatment with either SBRT or
      surgery.

PMID- 30298702
TI  - Synthesis and Evaluation of a 1,3a,6a-Triazapentalene (TAP)-Bonded System.
AB  - A method of synthesizing a directly connected 1,3a,6a-triazapentalene (TAP) ring
      system as a linearly bonded aromatic system with a planar form was established.
      Various TAP-dimers and a 2-alkyl-TAP-trimer were synthesized and their
      fluorescence properties were evaluated. Although the direct connection of the TAP
      ring with other TAP rings did not affect the fluorescence properties in diluted
      solvent, TAP-dimers showed unique fluorescence properties derived from the
      aggregation state under highly concentrated conditions. In particular, TAP-dimer
      5 f showed aggregation-induced emission in highly concentrated solution, and 5 b
      showed typical mechanochromic fluorescence in the solid state despite their
      compact molecular size.

PMID- 30298704
TI  - Comparison of skin autofluorescence, a marker of tissue advanced glycation end
      products in peritoneal dialysis patients using standard and biocompatible glucose
      containing peritoneal dialysates.
AB  - BACKGROUND: Heat sterilisation of peritoneal dialysis (PD) dialysates leads to
      the generation of advanced glycation products (AGEs), which can then deposit in
      the skin and be measured by skin autofluorescence (SAF). Newer biocompatible dual
      chamber dialysates contain less AGEs. We wished to determine whether the use of
      these newer dialysates resulted in lower SAF. METHODS: SAF was measured using the
      AGE reader, which directs ultraviolet light, intensity range 300-420 nm (peak 370
      nm) in patients established on PD for > 3 months using glucose containing
      dialysates. RESULTS: We screened 196 consecutive patients, and measured SAF in
      150; 86(57.3%) male, median age 62 (53-71) years, median duration of PD treatment
      17 (8.6-34.3) months. The median SAF was 3.48 (2.92-4.26) AU. The median SAF in
      the 57 (38%) patients prescribed biocompatible dual chamber bag dialysates was
      3.39 (2.69-3.98) vs 3.5 (3.05-4.54) for those using standard dialysates
      (p=0.044). Although prescription of biocompatible fluids was associated with SAF
      on univariate analysis, but not on multivariable testing, SAF was independently
      associated with Stoke-Davies co-morbidity grade (beta 0.045, 95% confidence
      limits (CL) 0.015 to 0.075, p=0.002), log duration of PD therapy (beta 0.051, CL
      0.001 to 0.101, p=0.045), white ethnicity (beta 0.066, CL 0.028 to 0.104,
      p=0.001), and negatively with serum albumin (beta -0.006, CL -0.008 to -0.004,
      p=0.014) CONCLUSIONS: Although SAF was lower in PD patients prescribed
      biocompatible dual chamber dialysates, on multivariable testing these dialysates
      were not independently associated with SAF. Other factors than PD fluid AGE
      content appear more important in determining SAF. This article is protected by
      copyright. All rights reserved.

PMID- 30298703
TI  - A 21.6 kDa tegumental protein of Clonorchis sinensis induces a Th1/Th2 mixed
      immune response in mice.
AB  - INTRODUCTION: Clonorchis sinensis is a major parasite affecting the Korea
      population. Despite the high infection rate and pathogenicity, very few studies
      have been conducted to investigate the immune responses against the proteins of
      C. sinensis. METHODS: In this study, in vitro immune response induced by a
      recombinant 21.6 kDa tegumental protein derived from C. sinensis (rCsTegu21.6)
      was confirmed in murine dendritic cells and T cells. For the in vivo analysis,
      each mouse was immunized three times. Total serum IgG and T cell cytokine
      production were determined by ELISA, while T cell proliferation was detected by a
      WST (Water-Soluble Tetrazolium salt)-1 assay. RESULTS: In vitro tests indicated
      that rCsTegu21.6 treatment increased the expression of surface molecules, such as
      CD40 (77%), CD80 (52%) and CD86 (46%), on murine dendritic cells and the
      secretion of cytokines (TNF-alpha, IL-6, IL-1beta, IL-10, and IL-12p70).
      Moreover, co-culturing dendritic cells activated by rCsTegu21.6 with allogenic T
      cells induced T cell proliferation over time. rCsTegu21.6 also stimulated
      specific antibody production and cytokine secretion [IL-2, IL-4, and interferon
      (IFN)-gamma)] from T cells following immunization in vivo. Notably, rCsTegu21.6
      predominantly induced IgG1 production and secretion of the Th2 cytokine IL-4,
      regardless of the type of adjuvant used. CONCLUSION: These results serve as a
      foundation for the development of tegumental protein-based vaccines against C.
      sinensis.

PMID- 30298705
TI  - Outcomes of intraocular lens scleral fixation with the friction knot technique.
AB  - PURPOSE: To examine the clinical outcomes of intraocular lens (IOL) scleral
      fixation with the friction knot technique. METHODS: Retrospective case series of
      152 eyes of 152 patients with inadequate capsular bag support operated with the
      friction knot IOL scleral fixation technique by a single surgeon. The fixated
      IOLs were one-piece or three-piece models all with open loop haptics. Main
      outcome measures were change in corrected distance visual acuity (CDVA) and
      postoperative complications. RESULTS: The mean follow-up time was 11.7 months
      (median 4.9, range 0.7-64.8). The mean logarithm of the minimum angle of
      resolution CDVA improved from preoperative 0.77 +/- 0.73 (Snellen 20/118 +/- 7.3
      lines) to 0.44 +/- 0.56 (Snellen 20/55 +/- 5.6 lines) at the final visit (p <
      0.001). The main postoperative complications were ocular hypertension (30.3%),
      uveitis-glaucoma-hyphaema syndrome (12.5%; UGHS), vitreous haemorrhage (11.2%)
      and retinal detachment (8.6%). Two (1.3%) cases of suture breakage were seen. In
      multivariate Cox regression analysis, age under 60 years [hazard ratio (HR) =
      5.41; 95% confidence interval (CI) 1.95-15.01] and scleral fixated one-piece IOL
      (HR = 4.23; 95% CI 1.44-12.44) were found as significant independent risk factors
      for developing new UGHS. CONCLUSION: The friction knot technique provides a firm
      scleral fixation. Scleral fixation may successfully be utilized in dislocated
      three-piece IOLs with loop haptics. We recommend avoiding scleral fixation of one
      piece IOLs in young patients due to a high risk of UGHS.

PMID- 30298706
TI  - Intracellular oxygen mapping using a myoglobin-mCherry probe with fluorescence
      lifetime imaging.
AB  - Oxygen (O2) is one of the most important biometabolites. In abundance, it serves
      as the limiting terminus of aerobic respiratory chains in the mitochondria of
      higher organisms; in deficit, it is a potent determinant of development and
      regulation of other physiological and therapeutic processes. Most knowledge on
      intracellular and interstitial concentration ([O2]) is derived from mitochondria
      isolated from cells or tissue biopsies, providing detailed but nonnative insight
      into respiratory chain function. The possible loss of essential metabolites
      during isolation and disruption of the normal interactions of the organelle with
      the cytoskeleton may cause these data to misrepresent intact cells. Several
      optical methodologies were also developed, but they are often unable to detect
      heterogeneity of metabolic characteristics among different individual cells in
      the same culture, and most cannot detect heterogeneous consumption within
      different areas of a single cell. Here, we propose a noninvasive and highly
      sensitive fluorescence lifetime microscopy probe, myoglobin-mCherry, appropriate
      to intracellular targeting. Using our probe, we monitor mitochondrial
      contributions to O2 consumption in A549 nonsmall cell lung cancer cells and we
      reveal heterogeneous [O2] within the intracellular environments. The
      mitochondrial [O2] at a single-cell level is also mapped by adding a peptide to
      target the probe to the mitochondria.

PMID- 30298707
TI  - Detection of IgE autoantibodies in mucous membrane pemphigoid and their
      association with disease severity.
AB  - BACKGROUND: Mucous membrane pemphigoid (MMP) is an autoimmune disease
      characterized by scarring lesions at mucosal sites. Although the pathogenic role
      of specific IgG and/or IgA has been already demonstrated and the detection of
      these immunoglobulins is a criterion in the diagnosis of MMP, little is known
      about IgE role in this disease. Therefore, the main purpose of this study was to
      assess the presence of circulating and tissue-bound IgE in patients with MMP and
      their possible correlations with clinical presentation and disease course.
      METHODS: We conducted a retrospective study on 29 patients affected by MMP,
      recruited from a single centre. Direct and indirect immunofluorescence studies
      were assessed to analyse the presence of specific IgE directed against the basal
      membrane zone. For each patient, fluorescence data were compared to clinical
      features. RESULTS: Linear deposits of C3, IgG and IgA were present in 86.2%, 62%
      and 37.9% of cases respectively, while IgE linear deposits were detected in 17
      out of 29 patients (58.6%) including one case with isolated IgE positivity.
      Circulating IgE and IgA anti-BMZ were present in 7 (24.1%) and 5 (17.2%)
      patients, respectively. Both the presence of circulating IgA and of tissue-bound
      IgE deposits correlated with disease activity index (P<0.014). CONCLUSIONS: Our
      results demonstrated the presence of IgE autoantibodies in MMP, particularly in
      more severe cases. Thus, IgE detection may represent an additional useful
      diagnostic tool in this disease.

PMID- 30298708
TI  - Keep your eyes wide open: how lifting the eyebrows can help exclude diagnosis of
      frontal fibrosing alopecia.

PMID- 30298709
TI  - Comparison of clinical and sonographic scores in hidradenitis suppurativa and
      proposal of a novel ultrasound scoring system.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory disease that
      presents with nodules, abscesses and fistulae affecting the apocrine gland
      bearing skin. Since few years, ultrasonography is used to better characterize HS
      skin lesions but comparison between clinical and sonographic scores has been made
      only in small series of patients. The aim is to assess concordance between
      clinical and sonographic scores in a larger cohort of HS patients. METHODS: We
      conducted a retrospective observational study on 140 HS patients comparing two
      clinical score systems, Hurley and HS-Physical Global Assessment (PGA), with two
      ultrasonographic scores, SOnographic Score of Hidradenitis Suppurativa (SOS-HS)
      and ultrasonographic HS-PGA, a novel ultrasound scoring system set up by our
      group. We used the weighted Cohen's Kappa statistic (k) to evaluate the
      agreement. RESULTS: Agreement between Hurley staging and SOS-HS was found in
      61.4% of patients (weighted kappa 0.477), while agreement between clinical and
      ultrasonography HS-PGA scores was found in 35% of patients (weighted kappa
      0.278), both findings suggesting a substantial disagreement. CONCLUSIONS: Our
      study demonstrated a relevant disagreement between clinical and ultrasonography
      scores. Ultrasonography discovered non-clinically evident HS lesions, notably
      fistulae. Taken together, the above findings may support the view, previously
      suggested in expert panel reports, on the higher sensitivity of ultrasonography
      compared to clinics in HS.

PMID- 30298710
TI  - Prostate specific antigen levels and proportion of biopsy positive cores are
      independent predictors of upgrading patterns in low risk prostate cancer.
AB  - BACKGROUND: To evaluate clinical factors associated with the risk of tumour
      upgrading patterns in low risk prostate cancer (PCA) patients undergoing radical
      prostatectomy. METHODS: In a period running from January 2013 to December 2016,
      245 low risk patients underwent RP. Patients were classified into three groups,
      which included case with pathology grade group one (no upgrading pattern), two
      three (intermediate upgrading pattern), and four-five (high upgrading pattern).
      The association of factors with the upgrading risk was evaluated by the
      multinomial logistic regression model. It was used a receiver operating
      characteristic (ROC) curve and area under the curve (AUC) analysis to assess the
      efficacy of predictors. RESULTS: Overall, tumor upgrading was detected in 158
      patients (67.3%). Tumour upgrading patterns were absent in 80 patients (32.7%),
      intermediate in 152 cases (62%) and high in 13 subjects (5.3%). Median prostate
      specific (PSA) levels and proportion of biopsy positive core (BPC) were higher in
      patients with intermediate (PSA = 6 ng/mL; BPC = 0.28) and high (PSA = 8.9 ng/mL;
      BPC = 0.33) than those without (PSA = 5.7 ng/mL; BPC = 0.17) and the difference
      was significant (PSA: p = 0.002; BPC: p = 0.001). When compared to not upgraded
      cases, higher BPC proportions were independent predictors of intermediate
      upgrading patterns (odds ratio, OR = 36.711; p < 0.0001; AUC = 0.613) while
      higher PSA values were independent predictors of high upgrading patterns
      (OR=2.033, p < 0.0001; AUC = 0.779). CONCLUSIONS: PSA and BPC were both
      independent predictors of tumour upgrading in low risk PCA. BPC associated with
      the risk of intermediate tumour upgrading patterns, but showed a low
      discrimination power. PSA associated with high upgrading patterns and showed a
      fair discrimination power in the model. Tumour upgrading risk patterns should be
      evaluated in low risk PCA patients before treatment.

PMID- 30298711
TI  - Intraprostatic Injections for LUTS/BPH treatment.
AB  - BACKROUND: Endoscopic surgical treatment represents the gold standard in patients
      with lower urinary tract symptoms (LUTS) when medical treatment fails. In the
      past years there has been a growing interest in intra-prostatic injections which
      represent a minimally invasive alternative for those patients not suitable for
      surgery. Aim of our study is to systematically review all the available data on
      intra-prostatic injections for the treatment of LUTS patients with benign
      prostatic enlargement (BPE). EVIDENCE ACQUISITION: A systematic review of the
      literature using the Medline, Scopus and Web of Science databases for relevant
      articles published until June 2018 was performed using both the Medical Subjects
      Heading and free test protocols. The MeSH search was conducted by combining the
      following terms: "Intra-prostatic Injections", "Botulinum Toxin A" "Onabotulinum"
      "Ethanol" "Lower Urinary tract Symptoms" "Benign prostatic enlargement" Benign
      Prostatic Hyperplasia" "NX1207" "PRX302". Each article's title and abstract were
      reviewed for their appropriateness and their relevance with regards to the
      relationship to intra-prostatic injections. EVIDENCE SYNTHESIS: Intra-prostatic
      injections for the treatment of LUTS/BPE patients may be performed using
      different products as: ethanol, onabotulinum toxin A, NX1207 and PRX 302.
      Ethanol, the first agent for intraprostatic use, showed promising results in
      prospective trials, however, the rare but serious adverse events associated with
      extraprostatic diffusion of ethanol stopped its use. Many studies on onabotulinum
      toxin A (BotoxR) have been performed, however, two large randomized clinical
      trials showed no differences in terms of symptoms improvements and flow
      improvements when compared to placebo. Two new promising drugs NX 1207 and PRX
      302 have been developped in the past years. NX 1207 showed lack of efficacy in
      the two large European phase III RCT. PRX 302 showed promising results in phase I
      and II studies, however, definitive results from a large phase III randomized
      controlled trial (RCT) are awaited before drawing any definitive conclusions.
      CONCLUSIONS: Intraprostatic injections are still to be considered investigational
      for the minimally invasive management of LUTS/BPE patients. Emerging data suggest
      a possible role of new agents in the near future when definitive data of ongoing
      RCTs will be available.

PMID- 30298712
TI  - Biological bases of radical prostatectomy in the management of prostate cancer
      patients with oligometastatic disease.

PMID- 30298713
TI  - Chemical Decoration of Perovskites by Nickel Oxide Doping for Efficient and
      Stable Perovskite Solar Cells.
AB  - Crystal engineering of CH3NH3PbI3- xCl x perovskite films through modification by
      decoration with p-type semiconductor materials was proposed as an efficient
      method for obtaining good-quality crystalline films. A simple method is
      demonstrated to improve the quality of perovskite films by adding nickel oxide
      (NiO x) nanoparticles into the precursor solution. The addition of NiO x brings
      about high-quality crystals and convenient photo-generated charge transport with
      reduced defect density owing to efficient control of the preferred nucleation and
      crystal growth. The sufficient contact between CH3NH3PbI3- xCl x-NiO x and the
      electron-transport layer can contribute to photo-generated carrier lifetime and
      transport through the optimized interface. Moreover, it is demonstrated that a
      strong chemical bonding interaction between MAPbI3- xCl x and NiO x could protect
      perovskite materials from oxygen and humidity corrosion, showing remarkable
      stability holding ~81% of the initial power conversion efficiency (PCE) after 50
      days. The device with the best PCE of 19.34% is achieved because of the improved
      short-circuit current from 22.23 to 23.01 mA cm-2 and fill factor from 68.97 to
      75.06%. The results certify that this p-type charge transport material decoration
      method for the optimization of perovskite films is an efficient way to optimize
      the performance.

PMID- 30298714
TI  - Facet-Inspired Core-Shell Gold Nanoislands on Metal Oxide Octadecahedral
      Heterostructures: High Sensing Performance toward Sulfide in Biotic Fluids.
AB  - The development of structurally modified metal oxide heteroarchitectures with
      higher energy facets exposed has been of extensive research interests because of
      their unique construction and synergy effect of multifunctioning characteristics.
      In this study, we reported for the first time the development of a distinct type
      of gold nanoislands (AuNIs) on metal oxides (i.e., Cu2O-CuO) octadecahedral (ODH)
      heterostructures through the galvanic exchange reaction, where Cu2O not only acts
      as a stabilizer but also functions as a reductant. The electrocatalytic
      performance of the resultant core-shell Cu2O-CuO@AuNI ODH-based electrochemical
      sensing platform has been evaluated in ultrasensitive detection of sulfide as
      early disease diagnostics and bacterial marker. Owing to the synergistic
      collaboration of enhanced surface active sites, exposed {110} crystallographic
      facets, mixed valances of copper that encourage redox reactions at electrode
      material/analyte interface, and the polarization effect provide by AuNIs
      decorated onto the Cu2O surface, Cu2O-CuO@AuNI ODH-modified electrode has
      demonstrated striking electrochemical sensing performance toward sulfide
      oxidation in terms of broad linear range, real detection limit down to 1 nM (S/N
      = 3), and incredible durability and reproducibility. In virtue of marvelous
      efficiency, the proposed electrochemical sensor based on Cu2O-CuO@AuNI ODH has
      been employed in in situ sensitive detection of a ubiquitous amount of sulfide
      engendered by sulfate-reducing bacteria and real-time tracking of sulfide efflux
      from live cells as early diagnostic strategies.

PMID- 30298715
TI  - Characterization of Mechanical Degradation in Perfluoropolyether Film for Its
      Application to Antifingerprint Coatings.
AB  - Enhancing the mechanical durability of antifingerprint films is critical for its
      industrial application on touch-screen devices to withstand friction damage from
      repeated rubbing in daily usage. Using reactive molecular dynamics simulations,
      we herein implement adhesion, mechanical, and deposition tests to investigate two
      durability-determining factors: intrachain and interchain strength, which affect
      the structural stability of the antifingerprint film (perfluoropolyether) on
      silica. From the intrachain perspective, it is found that the Si-C bond in the
      polymer chain is the weakest, and therefore prone to dissociation and potentially
      forming a C-O bond. This behavior is demonstrated consistently, regardless of the
      cross-linking density between polymer chains. For the interchain interaction,
      increasing the chain length enhances the mechanical properties of the film.
      Furthermore, the chain deposition test, mimicking the experimental coating
      process, demonstrates that placing shorter chains first to the surface of silica
      and then depositing longer chains is an ideal way to improve the interchain
      interaction in the film structure. The current study reveals a clear pathway to
      optimize the configuration of the polymer chain as well as its film structure to
      prolong the product life of the coated antifingerprint film.

PMID- 30298716
TI  - Carbon Excess C3N: A Potential Candidate as Li-Ion Battery Material.
AB  - Xu et al.'s recent experimental work ( Adv. Mater. 2017, 29, 1702007) suggested
      that C3N is a potential candidate as Li-ion battery with unusual electrochemical
      characteristics. However, the obvious capacity loss (from 787.3 to 383.3 mA h.g
      1) occurs after several cycles, which restricts its high performance. To
      understand and further solve this issue, in the present study, we have studied
      the intercalation processes of Li ions into C3N via first-principle simulations.
      The results reveal that the Li-ion theoretical capacity in pure C3N is only
      133.94 mA h.g-1, the value is obviously lower than experimental one. After
      examining the experimental results in detail, it is found that the chemical
      component of the as-generated C xN structure is actually C2.67N with N excess. In
      this case, the calculated theoretical capacity is 837.06 mA h.g-1, while part of
      Li ions are irreversibly trapped in C2.67N, resulting in the capacity loss. This
      phenomenon is consistent with the experimental results. Accordingly, we suggest
      that N excess C3N, but not pure C3N, is the proposed Li-ion battery material in
      Xu et al.'s experiment. To solve the capacity loss issue and maintain the
      excellent performance of C3N-based anode material, the C3N with slightly excess C
      (C3.33N), which has been successfully fabricated in the experiment, is considered
      in view of its relatively low chemical activity as compared with N excess C3N.
      Our results reveal that the C excess C3N is a potential Li-ion battery material,
      which exhibits the low open circle voltage (0.12 V), high reversible capacity
      (840.35 mA h.g-1), fast charging/discharging rate, and good electronic
      conductivity.

PMID- 30298717
TI  - Role of Bimolecular Exciton Kinetics in Controlling the Efficiency of Organic
      Light-Emitting Diodes.
AB  - Here, we have carried out a spectroscopic investigation on the operational
      organic light-emitting diodes (OLEDs) to determine the role of emission layer
      thickness on the optoelectronic performance of OLEDs based on a poly(9,9
      dioctylfluorene- alt-benzothiadiazole) (F8BT) copolymer system. Our study shows
      that delayed fluorescence (DF) via triplet-triplet annihilation (TTA) contributes
      significantly to boost the OLED efficiency through its fractional contribution.
      Interestingly, we note that DF contribution varies as a function of the emissive
      layer thickness. From the time-resolved electroluminescence (TREL) and triplet
      absorption (under electrical excitation) studies, we have seen that the emissive
      layer thickness controls triplet exciton generation and decay processes. From
      TREL, we have also shown that singlet-triplet annihilation (STA) is the dominant
      fluorescence quenching mechanism in bulk of the emissive layer, whereas thinner
      devices have significant exciton quenching at the interface of the injection
      layer/F8BT. The strength of STA differs in thin versus thick samples, which has
      been correlated with the spectral & spatial overlap integral of singlet and
      triplet states. Hence, STA strength and triplet population density are critical
      parameters for an explanation of high efficiency in unusually thick F8BT OLEDs.

PMID- 30298718
TI  - Prolonged Drug-Releasing Fibers Attenuate Alzheimer's Disease-like Pathogenesis.
AB  - Delivering drugs and agents to the brain is a huge challenge, especially for
      chronic neurodegenerative disorders, such as Alzheimer's disease (AD). For this,
      prolonged and sustained release methods to increase brain uptake represent an
      impacting concept. The bioresorbable polymer poly-lactic acid (PLA) has high
      potential for medical implants; at the same time, glucagon-like peptide-1 (GLP-1)
      analogues have considerable neuroprotective attributes and represent a
      therapeutic strategy for AD. Here, a biodevice is produced by electrospinning PLA
      with a GLP-1 analogue (liraglutide, LG), coated with a thin layer of gelatin. The
      biodevice is subcutaneously implanted in a transgenic mouse model of AD and LG is
      released for 14 days in mice serum. After 4 weeks of implantation, crucial
      hallmarks of the AD are highly diminished: hippocampal senile amyloid beta plaque
      load and neuroinflammatory markers. Furthermore, neurogenesis is enhanced in the
      subventricular zone, an important neurogenic niche in the brain. The designed
      biodevice holds great promise for being an affordable candidate to act as a
      prolonged drug provider, promoting LG mission through increasing its lifetime,
      constituting a relevant approach for old and impaired brain.

PMID- 30298719
TI  - Tumor Targeting and Lipid Rafts Disrupting Hyaluronic Acid-Cyclodextrin-Based
      Nanoassembled Structure for Cancer Therapy.
AB  - CD44 receptor targeting and lipid rafts destroying nanoassembly (NA) was
      developed for breast cancer therapy. Methyl-beta-cyclodextrin (MbCD), as a
      cholesterol depletion moiety, was conjugated to hyaluronic acid-ceramide (HACE)
      structure via an ester linkage. HACE-MbCD NA with 198 nm hydrodynamic size,
      unimodal size distribution, and spherical shape was fabricated by self-assembly
      strategy. By filipin III staining, it was identified that HACE-MbCD NA extracted
      cholesterol from the cellular membrane of MDA-MB-231 (human breast
      adenocarcinoma) cells more efficiently rather than MbCD and HACE NA. Efficient
      lipid rafts disruption of HACE-MbCD NA compared to MbCD and HACE NA groups seems
      to lead to the increment in apoptosis and antiproliferation efficiencies in MDA
      MB-231 cells. Improvement in tumor targeting efficiency of HACE-MbCD NA compared
      to HACE NA in MDA-MB-231 tumor-bearing mice can be explained by the extraction
      process of cellular cholesterol by MbCD. Following intravenous injection in MDA
      MB-231 tumor-bearing mice, the most efficient suppression of tumor growth and
      highest apoptotic region were observed in HACE-MbCD NA group rather than MbCD
      group. All of these findings suggest that CD44 receptor-targetable HACE-MbCD NA
      retaining cholesterol depletion activity from cancer cells may be one of the
      remarkable nanosystems for breast cancer therapy.

PMID- 30298720
TI  - Fabrication of Ge:Ga Hyperdoped Materials and Devices Using CMOS-Compatible Ga
      and Ge Hydride Chemistries.
AB  - We report a versatile chemical vapor deposition (CVD) method to dope Ge films
      with Ga atoms in situ over a wide concentration range spanning from 3 * 1018 to
      2.7 * 1020 cm-3. The method introduces a stable and volatile Ga hydride
      [D2GaN(CH3)2]2 that reacts readily with Ge4H10 to deliver Ga dopants controllably
      and systematically at complementary metal-oxide-semiconductor compatible ultralow
      temperatures of ~360  degrees C. Thick and monocrystalline layers (1.3 MUm) are
      produced on Si substrates at growth rates approaching 50 nm/min. The doped
      crystals are fully epitaxial and devoid of misfit defects and Ga precipitates as
      evidenced by Rutherford backscattering spectrometry, X-ray diffraction, and cross
      sectional transmission electron microscopy. The Ga contents measured by secondary
      ion mass spectrometry and the active carrier concentrations determined by
      spectroscopic ellipsometry (as well as Hall effect measurements in several cases)
      are in close agreement, indicating near full activation. Photoluminescence
      spectra show a strong emission peak at 0.79 eV corresponding to the direct gap E0
      transition, evidence of the indirect transition, and additional structures
      characteristic of p-type Ge. Electroluminescence and I- V curves measured from
      p(Ga)-i-n photodiodes are found to be at par with those from boron-based
      reference devices. These results are promising and demonstrate that a single
      source CVD approach allows independent control of Ga doping level and junction
      depth, producing flat dopant profiles, high activation ratios, uniform
      distributions, and sharp interfaces. This method potentially represents a viable
      alternative to state-of-the-art boron-based p-type doping and activation of Ge
      like materials.

PMID- 30298721
TI  - Antibacterial Micelles with Vancomycin-Mediated Targeting and pH/Lipase-Triggered
      Release of Antibiotics.
AB  - Antibiotic delivery systems play an important role in increasing the efficacy
      while reducing the off-target toxicity and antibiotic resistance. Though
      bacterial infections share pathophysiological pathways similar to tumor tissues,
      few delivery systems have achieved bacterial targeting and on-demand release of
      antibiotics. In the current study, amphiphilic poly(ethylene glycol)-poly(epsilon
      caprolactone) (PECL) copolymers are conjugated with vancomycin (VAN) as targeting
      ligands via pH-cleavable hydrazone bonds to obtain micelle carriers (Van-hyd
      PECL). Subsequently, ciprofloxacin (CIP) is encapsulated to obtain Van-hyd
      PECL/Cip micelles with an average size of 77 nm and a CIP loading amount of 4.5%.
      The poly(ethylene glycol) shells and the extension of VAN moieties on the micelle
      surface enhance the blood circulation and selective recognition of bacteria. The
      deshielding of VAN shells under acidic conditions disrupts the
      hydrophobic/hydrophilic balance leading to an increase in micelle sizes, which
      facilitates the degradation of poly(epsilon-caprolactone) by lipase overexpressed
      in the infection site and the release of encapsulated CIP for bacterial
      destruction. The micelle treatment has improved the survival of Pseudomonas
      aeruginosa-infected mice and reduced the bacterial burdens and alveolar injuries
      in lungs, compared with free drugs and micelles without inoculation of VAN
      moieties. Three doses of Van-hyd-PECL/Cip micelles further extend the animal
      survival, decrease the bacterial colonization in lungs, and almost restore the
      normal alveolar microstructure. In this regard, this study has demonstrated a
      strategy to enhance the bacterial targeting of micelles via an antibiotic (VAN)
      and to sequentially trigger the release of antibiotics (VAN and CIP) at the
      infection site.

PMID- 30298722
TI  - Repairing Defects of Halide Perovskite Films To Enhance Photovoltaic Performance.
AB  - On account of the low-temperature solution fabrication, the much high defect
      density at the interfaces and grain boundaries of halide perovskite films is
      recognized as one of the big obstacles toward high-efficiency solar cells. Here,
      the time-resolved photoluminescence (TRPL) with incident light exciting from the
      upper surface and bottom of halide perovskite films, respectively, showed very
      different results, verifying the much more surface trap states in the film. To
      eliminate the defects and enhance the photovoltaic properties of perovskite solar
      cells (PSCs), we designed a facile and effective method to repair the defects of
      the perovskite film using formamidinium iodine (FAI) solution. The dissociative
      FA+ and I- ions could compensate for the loss of volatile organic cations and
      also fill the I- vacancies of halide perovskites. After repairing defects with
      proper concentration of FAI solution, the TRPL curves obtained by light exciting
      from the different sides of the perovskite film nearly overlap together,
      indicating the reduction of surface traps. As a result, both the total carrier
      lifetime and charge extractions were improved by removing the nonradiative
      channels (surface traps), which universally enhanced the power conversion
      efficiency and stability of the planar heterojunction structural PSCs.

PMID- 30298723
TI  - Structure-Property of Lithium-Sulfur Nanoparticles via Molecular Dynamics
      Simulation.
AB  - Lithium-sulfur (Li-S) batteries offer higher energy densities than most reported
      lithium-ion batteries. However, our understanding of Li-S battery is still
      largely unknown at the level of the nanoscale. The structural properties of Li-S
      materials were investigated via molecular dynamics (MD) simulations using the
      ReaxFF force field. Several Li-S nanoparticles with different Li/S composition
      ratios (2:1 and 2:8) and various structures are studied. Our MD simulations show
      that among the four structures we constructed for Li2S8 nanoparticles, the core
      shell structure is the most thermodynamically stable one during the charging
      (delithiation) process. In contrast to bulk crystal Li2S, we find the presence of
      mixed lithium sulfide and polysulfide species are common features for these Li-S
      (Li2S, Li2S8) nanoparticles. The complex distribution of these sulfide and
      polysulfide speciation are dictated by both stoichiometry and local atomic
      structures in the nanoparticle. These findings will provide insight into further
      development of functionalized lithium-sulfur cathodes.

PMID- 30298724
TI  - Scalable, High-Performance Printed InO x Transistors Enabled by Ultraviolet
      Annealed Printed High- k AlO x Gate Dielectrics.
AB  - Inorganic transparent metal oxides represent one of the highest performing
      material systems for thin-film flexible electronics. Integrating these materials
      with low-temperature processing and printing technologies could fuel the next
      generation of ubiquitous transparent devices. In this work, we investigate the
      integration of UV-annealing with inkjet printing, demonstrating how UV-annealing
      of high- k AlO x dielectrics facilitates the fabrication of high-performance InO
      x transistors at low processing temperatures and improves bias-stress stability
      of devices with all-printed dielectrics, semiconductors, and source/drain
      electrodes. First, the influence of UV-annealing on printed metal-insulator-metal
      capacitors is explored, illustrating the effects of UV-annealing on the
      electrical, chemical, and morphological properties of the printed gate
      dielectrics. Utilizing these dielectrics, printed InO x transistors were
      fabricated which achieved exceptional performance at low process temperatures
      (<250  degrees C), with linear mobility MUlin ~ 12 +/- 1.6 cm2/V s, subthreshold
      slope <150 mV/dec, Ion/ Ioff > 107, and minimal hysteresis (<50 mV). Importantly,
      detailed characterization of these UV-annealed printed devices reveals enhanced
      operational stability, with reduced threshold voltage ( Vt) shifts and more
      stable on-current. This work highlights a unique, synergistic interaction between
      low-temperature-processed high- k dielectrics and printed metal oxide
      semiconductors.

PMID- 30298725
TI  - Identification of Myricetin as an Ebola Virus VP35-Double-Stranded RNA
      Interaction Inhibitor through a Novel Fluorescence-Based Assay.
AB  - Ebola virus (EBOV) is a filovirus that causes a severe and rapidly progressing
      hemorrhagic syndrome; a recent epidemic illustrated the urgent need for novel
      therapeutic agents because no drugs have been approved for treatment of Ebola
      virus. A key contribution to the high lethality observed during EBOV outbreaks
      comes from viral evasion of the host antiviral innate immune response in which
      viral protein VP35 plays a crucial role, blocking interferon type I production,
      first by masking the viral double-stranded RNA (dsRNA) and preventing its
      detection by the pattern recognition receptor RIG-I. Aiming to identify
      inhibitors of the interaction of VP35 with the viral dsRNA, counteracting the
      VP35 viral innate immune evasion, we established a new methodology for high-yield
      recombinant VP35 (rVP35) expression and purification and a novel and robust
      fluorescence-based rVP35-RNA interaction assay ( Z' factor of 0.69). Taking
      advantage of such newly established methods, we screened a small library of
      Sardinian natural extracts, identifying Limonium morisianum as the most potent
      inhibitor extract. A bioguided fractionation led to the identification of
      myricetin as the component that can inhibit rVP35-dsRNA interaction with an IC50
      value of 2.7 MUM. Molecular docking studies showed that myricetin interacts with
      the highly conserved region of the VP35 RNA binding domain, laying the basis for
      further structural optimization of potent inhibitors of VP35-dsRNA interaction.

PMID- 30298726
TI  - Novel Strategy for the Investigation on Chirality Selection of Single-Walled
      Carbon Nanotubes with DNA by Electrochemical Characterization.
AB  - There is a correlation between specific bases of DNA molecules and the chirality
      of single-walled carbon nanotubes (SWNTs), which contributes the recognition
      ability of DNA toward partner species of chiral SWNTs. A novel strategy of
      electrochemical characterization is reported here for the investigation on
      chirality selection of (7,6) and (6,5) SWNTs with various DNA sequences, and it
      is found that both DNA strand length and sequence composition significantly
      affected the interaction of chiral SWNTs with DNA. Then (7,6) and (6,5) SWNTs
      were distinguished from each other with DNA sequences chosen by electrochemical
      methods, which demonstrated an effective and excellent feasibility for the
      strategy and presented a new insight into DNA-SWNT applications. This strategy
      can also be applied to more chiral SWNTs and DNA sequence recognition and may
      serve as a prescreening method for the recognition and separation of single
      chirality SWNTs, which would be a new contribution to the further development of
      DNA-SWNT hybrids.

PMID- 30298727
TI  - Photoelectrochemical-Chemical-Chemical Redox Cycling for Advanced Signal
      Amplification: Proof-of-Concept Toward Ultrasensitive Photoelectrochemical
      Bioanalysis.
AB  - Signal amplification is essential for ultrasensitive photoelectrochemical (PEC)
      bioanalysis. Exploration of the facile and efficient route for multiple signal
      amplification is highly appealing. Herein, we present the concept of
      photoelectrochemical-chemical-chemical (PECCC) redox cycling as an advanced
      signal amplification route and a proof-of-concept toward ultrasensitive PEC
      bioanalysis. The system operated upon the bridging between the enzymatic
      generation of signaling species ascorbic acid (AA) from a sandwich immunoassay
      and the PECCC redox cycling among the ferrocenecarboxylic acid as redox mediator,
      the AA, and the tris(2-carboxyethyl)phosphine as reducing agent at the
      Bi2S3/Bi2WO6 photoelectrode. Exemplified by myoglobin (Myo) as target, the
      proposed system achieved efficient regeneration of AA and thus signal
      amplification toward the ultrasensitive split-type PEC immunoassay. This work
      first exploited the PECCC redox cycling, and we believe it will attract more
      interest in the research of PEC bioassays on the basis of advanced redox cycling.

PMID- 30298728
TI  - Application of Experimental Polystyrene Partition Constants and Diffusion
      Coefficients to Predict the Sorption of Neutral Organic Chemicals to Multiwell
      Plates in in Vivo and in Vitro Bioassays.
AB  - Sorption to the polystyrene (PS) of multiwell plates can affect the exposure to
      organic chemicals over time in in vitro and in vivo bioassays. Experimentally
      determined diffusion coefficients in PS ( DPS) were in a narrow range of 1.25 to
      8.0 . 10-16 m2 s-1 and PS-water partition constants ( KPS/w) ranged from 0.04 to
      5.10 log-units for 22 neutral organic chemicals. A kinetic model, which
      explicitly accounts for diffusion in the plastic, was applied to predict the
      depletion of neutral organic chemicals from different bioassay media by sorption
      to various multiwell plate formats. For chemicals with log Kow > 3, the medium
      concentrations decreased rapidly and considerably in the fish embryo toxicity
      assay but medium concentrations remained relatively constant in the cell-based
      bioassays with medium containing 10% fetal bovine serum (FBS), emphasizing the
      ability of the protein- and lipid-rich medium to compensate for losses by
      multiwell plate sorption. The PS sorption data may serve not only for exposure
      assessment in bioassays but also to model the contaminant uptake by and release
      from plastic packaging material and the chemical transport by PS particles in the
      environment.

PMID- 30298729
TI  - Deposition Mapping of Polycyclic Aromatic Compounds in the Oil Sands Region of
      Alberta, Canada and Linkages to Ecosystem Impacts.
AB  - This study produced gridded deposition estimates of polycyclic aromatic compounds
      (PACs), including 17 polycyclic aromatic hydrocarbons (PAHs), 21 alkylated PAHs
      (alk-PAHs), and 5 dibenzothiophenes (DBTs), over the oil sands region of Alberta,
      Canada and surrounding communities. Gridded annual total deposition of PACs in
      2011 ranged from 55 to 175 000 MUg m-2 yr-1 and the mean and median fluxes were
      1700 and 760 MUg m-2 yr-1, respectively. The domain-wide mean dry and wet
      deposition were 600 and 1100 MUg m-2 yr-1. PAHs, alk-PAHs and DBTs contributed
      19%, 74%, and 7% to the total dry deposition, and 42%, 49%, and 9% to the total
      wet deposition. Dominant chemical species contributing to total deposition were
      naphthalene, retene and phenanthrene for PAHs and C2
      benz[a]anthracene/triphenylene/chrysene, C2-fluoranthene/pyrene and C2-fluorene
      for alk-PAHs. The highest PAC deposition was found over the surface mineable
      area, which received 9 times the deposition flux of outlying areas. Additional
      deposition hotspots were also observed south of the surface mineable area notably
      over in situ bitumen production sites. The deposition of alk-PAHs impacted a more
      extensive area than that of PAHs or DBTs. This result suggests that atmospheric
      deposition is a key process in wildlife exposure to PACs across the region.

PMID- 30298730
TI  - Bioaccumulation, Biotransformation, and Synergistic Effects of Binary Fungicide
      Mixtures in Hyalella azteca and Gammarus pulex: How Different/Similar are the Two
      Species?
AB  - Aquatic organisms are consistently exposed to a mixture of micropollutants that
      can bioaccumulate, undergo biotransformation, and may exert mixture effects.
      However, little is known on the underlying mechanisms and species-specificity.
      Herein we investigated bioaccumulation, biotransformation and synergistic effects
      of azole (i.e., prochloraz) and strobilurin (i.e., azoxystrobin) fungicides in
      the two aquatic invertebrate species, Hyalella azteca and Gammarus pulex.
      Bioaccumulation of azoxystrobin was similar, whereas bioaccumulation of
      prochloraz was slightly different in the two species but was still significantly
      below the REACH criteria for bioaccumulative substances. Similar
      biotransformation patterns were observed in both species, and only a few unique
      biotransformation reactions were detected in H. azteca such as malonyl-glucose
      and taurine conjugation. Toxicokinetic modeling additionally indicated that
      biotransformation is a more important elimination pathway in H. azteca. In
      mixtures, no-observed-adverse-effect levels of prochloraz decreased the LC50s of
      azoxystrobin in both species which correlated well with increased internal
      azoxystrobin concentrations. This synergistic effect is partly due to the
      inhibition of cytochrome P450 monooxygenases by prochloraz which subsequently
      triggered the reduced biotransformation of azoxystrobin (lower by five folds in
      H. azteca). The largely similar responses in both species suggest that the easier
      to-cultivate H. azteca is a promising representative of invertebrates for
      toxicity testing.

PMID- 30298731
TI  - Accuracy, Repeatability, and Limitations for Determination of Chemical Activities
      from Vapor Pressure Osmometry.
AB  - Vapor pressure osmometry presents a convenient method to measure chemical
      activity. The work presented here was carried out to provide confidence in using
      this technique for a VPO model that does not utilize the "hanging-drop" method.
      While validation studies are available for certain models of vapor pressure
      osmometers, none were located for the UIC Jupiter 833 osmometer. This study
      addresses that need by providing a comparison between original experimental data
      on sodium chloride, calcium chloride, and sodium sulfate solutions to values
      calculated using the Pitzer equations. A comparison is also made for experimental
      data on sucrose with a literature correlation. This study briefly reviews the
      assumptions going into the equation used to relate the osmometer signal to the
      diluent activity in order to identify potential sources of the error and the
      noise in the data. The experimental data shows that the UIC 833 osmometer yields
      diluent activity values accurate to an average of 0.02%, allowing calculation of
      osmotic coefficients and solute activity coefficients. Further studies need to be
      conducted on the accuracy at concentrations above 1.4 m. Qualitatively, however,
      comparison suggests the UIC Jupiter 833 osmometer yields more scatter in the
      experimental data than the Knauer instruments. Using more uniform mesh caps on
      the thermistors could possibly reduce that scatter. Finally, we show that
      replacing the glass thermistors with in-house made thermistors with Teflon
      incorporated in the structure give reproducible results and that certain
      modifications to the design are possible without losing accuracy in the
      measurements.

PMID- 30298732
TI  - Boosting Modulation of Oxide Semiconductors via Voltage-Based Ambi-Ionic
      Migration.
AB  - In recent years, high-performance amorphous oxide semiconductor thin-film
      transistor (AOS TFT) technology is required to meet the increasing demand for
      novel displays, such as rollable, transparent, or augmented reality head-up
      displays. It has been demonstrated that voltage-based modulation techniques for
      AOS-based active layers can achieve high-performance AOS TFTs. The voltage-based
      modulation technique allows specific ions to migrate into the active layer
      depending on the polarity of the applied voltage, thus easily modulating the
      active layer. Additionally, potassium superoxide (KO2) solution is employed in
      AOS TFTs as a source of potassium (K+) and highly reactive superoxide radical
      (O2*-) ions. The K+ and O2*- ions in the KO2 solution are controlled by an
      applied voltage bias and rapidly migrate into the active layer, directly changing
      its chemical composition and electrical properties. AOS TFTs that use this
      technique exhibit better electrical performance than conventional AOS TFTs: the
      field-effect mobility improved from 10.05 to 15.31 cm2/V.s; the subthreshold
      swing decreased from 0.44 to 0.33 V/dec; the Ion/off ratio increased from 1.24 *
      107 to 3.17 * 108; and the threshold voltage shift decreased from 5.2 to 3.4 V
      under a positive bias stress test conducted over 10 000 s. Ultimately, this
      approach to modulating the internal ion distribution in oxide semiconductors
      could provide opportunities for various AOS devices to attain desirable
      electrical characteristics.

PMID- 30298733
TI  - One-Pot Approach for the Synthesis of Bis-indole-1,4-disubstituted-1,2,3
      triazoles.
AB  - A new strategy for the synthesis of bis-indoletriazoles was developed using a
      sequential one-pot four-step procedure via I2 and H2SO4-SiO2 catalyzed Friedel
      Crafts reactions of indole with aldehyde followed by N-alkylation with propargyl
      bromide, azidation, and copper(I)-catalyzed azide alkyne cycloaddition (CuAAC).
      The reaction proceeded smoothly at room temperature in a short time, and a series
      of bis-indoletriazoles were obtained in good to excellent yields proving the
      generality of this one-pot methodology.

PMID- 30298734
TI  - Proteogenomics of Adenosine-to-Inosine RNA Editing in the Fruit Fly.
AB  - Adenosine-to-inosine RNA editing is one of the most common types of RNA editing,
      a posttranscriptional modification made by special enzymes. We present a
      proteomic study on this phenomenon for Drosophila melanogaster. Three proteome
      data sets were used in the study: two taken from public repository and the third
      one obtained here. A customized protein sequence database was generated using
      results of genome-wide adenosine-to-inosine RNA studies and applied for
      identifying the edited proteins. The total number of 68 edited peptides belonging
      to 59 proteins was identified in all data sets. Eight of them being shared
      between the whole insect, head, and brain proteomes. Seven edited sites belonging
      to synaptic vesicle and membrane trafficking proteins were selected for
      validation by orthogonal analysis by Multiple Reaction Monitoring. Five editing
      events in cpx, Syx1A, Cadps, CG4587, and EndoA were validated in fruit fly brain
      tissue at the proteome level using isotopically labeled standards. Ratios of
      unedited-to-edited proteoforms varied from 35:1 ( Syx1A) to 1:2 ( EndoA). Lys-137
      to Glu editing of endophilin A may have functional consequences for its
      interaction to membrane. The work demonstrates the feasibility to identify the
      RNA editing event at the proteome level using shotgun proteomics and customized
      edited protein database.

PMID- 30298735
TI  - Pd(II)/Norbornene-Catalyzed Meta-C-H Alkylation of Nosyl-Protected
      Phenylalanines.
AB  - A Pd/norbornene-catalyzed direct meta-alkylation of nosyl-protected phenylalanine
      derivatives with alkyl iodides is reported in moderate to good yields. The use of
      diisopropyl bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate is identified as a more
      suitable transient mediator. A simple pyridine ligand is also essential for this
      reaction to proceed. No racemization was observed in this meta-methylation
      reaction.

PMID- 30298736
TI  - Antileishmanial Carbasugars from Geosmithia langdonii.
AB  - Two new carbasugar-type metabolites, (1 S,2 R,3 R,4 R,5 R)-2,3,4-trihydroxy-5
      methylcyclohexyl-2',5'-dihydroxybenzoate (1) and (1 S,2 S,3 S,4 R,5 R)-4-[(2',5'
      dihydroxybenzyl)oxy]-5-methylcyclohexane-1,2,3-triol (2), were isolated from the
      filamentous fungus Geosmithia langdonii isolated from cotton textiles from
      Assiut, Egypt. The structures of 1 and 2 were elucidated based on comprehensive
      1D and 2D NMR and MS data. Compounds 1 and 2 showed antileishmanial activity
      against Leishmania donovani with IC50 values of 100 and 57 MUM, respectively. The
      (1 S,2 R,3 R,4 R,5 R) absolute configuration of carbasugar 1 was assigned via 2D
      NMR and experimental and calculated electronic circular dichroism (ECD) data.
      Similarly, the tentative structure of compound 2 was shown to possess a (1 S,2
      S,3 S,4 R,5 R) absolute configuration via comparing its experimental ECD data and
      the specific rotation with 1 as well as examining the energy-minimized 3D
      computational models of compounds 1 and 2.

PMID- 30298737
TI  - Nanofilamentous Virus-Based Dynamic Hydrogels with Tunable Internal Structures,
      Injectability, Self-Healing, and Sugar Responsiveness at Physiological pH.
AB  - With expanding applications of hydrogels in diverse fields ranging from
      biomaterials to sensors, actuators, and soft robotics, there is an urgent need to
      endow one single gel with multiple physicochemical properties, such as stimuli
      responsiveness, injectability, self-healing, and tunable internal structures.
      However, it is challenging to simultaneously incorporate these highly sought
      after properties into one single gel. Herein, a conceptual hydrogel system with
      all of these properties is presented via combining bioconjugate chemistry,
      filamentous viruses, and dynamic covalent bonds. Nanofilamentous bioconjugates
      with diol affinity were prepared by coupling a tailor-synthesized low-p Ka
      phenylboronic acid (PBA) derivative to a well-defined green nanofiber the M13
      virus with a high aspect ratio (PBA-M13). Dynamic hydrogels with tunable
      mechanical strength were prepared by using multiple diol-containing agents such
      as poly(vinyl alcohol) to cross-link such PBA-M13 via the classic boronic-diol
      dynamic bonds. The as-prepared hydrogels exhibit excellent injectability and self
      healing behaviors as well as easy chemical accessibility of the PBA moieties on
      the virus backbone inside the gel matrix. Ordered internal structures were
      imparted into virus-based hydrogels by simple shear-induced alignment of the
      virus nanofibers. Furthermore, unique hydrogels with chiral internal structures
      were fabricated through in situ gelation induced by diffusion of diol-containing
      molecules to fix the chiral liquid crystal phase of the PBA-M13 virus. Sugar
      responsiveness of this gel leads to a glucose-regulated release behavior of
      payloads such as insulin. All of these properties have been implemented at
      physiological pH, which will facilitate future applications of these hydrogels as
      biomaterials.

PMID- 30298739
TI  - Selective Synthesis of Aminoisoquinolines via Rh(III)-Catalyzed C-H/N-H Bond
      Functionalization of N-Aryl Amidines with Cyclic 2-Diazo-1,3-diketones.
AB  - A simple C-H/N-H bond functionalization of N-aryl amidines with cyclic 2-diazo
      1,3-diketones for the synthesis of 1-aminoisoquinolines has been accomplished by
      employing [Cp*RhCl2]2/CsOPiv as the catalyst system. This methodology proceeds by
      a cascade C-H activation/intramolecular cyclization under mild reaction
      conditions, features a broad substrate scope, and involves the formation of two
      new sigma bonds (C-C and C-N) in a single operation for the construction of novel
      1-aminoisoquinoline skeletons in good to excellent yields.

PMID- 30298740
TI  - Matrine-Type Alkaloids from the Roots of Sophora flavescens and Their Antiviral
      Activities against the Hepatitis B Virus.
AB  - Eight new matrine-type alkaloids, flavesines G-J (1-4), alopecurine B (5), 7,11
      dehydro-oxymatrine (6), 10-oxy-5,6-dehydromatrine (7), and 10-oxysophoridine (8),
      along with nine known analogues (9-17) were isolated from the roots of Sophora
      flavescens. Compounds 1-3 are the first natural matrine-type alkaloids with an
      open-loop ring D, while compound 4 represents an unprecedented dimerization
      pattern constructed from matrine and piperidine, and 5 is the first example of a
      matrine-type alkaloid with cleavage of the C-5-C-6 bond. The new structures were
      elucidated by means of spectroscopic data analysis (including NMR, MS, IR, and
      UV), and the absolute configurations were determined using single-crystal X-ray
      diffraction and ECD data. The isolated alkaloids were evaluated for their
      antiviral activity against hepatitis B virus, and compounds 1, 4, 5, 10, and 14
      exhibited comparable antiviral potencies to matrine.

PMID- 30298738
TI  - Risks Related to High-Dosage Recombinant Antimicrobial Peptide Microcin J25 in
      Mice Model: Intestinal Microbiota, Intestinal Barrier Function, and Immune
      Regulation.
AB  - Antimicrobial peptide (AMP) can be a promising alternative in various domains.
      However, further risk information is required. In this study, mice were orally
      administrated different dosages of recombinant AMP microcin J25 (4.55, 9.1, and
      18.2 mg/kg; MccJ25) for 1 week, and the toxicity risk impacts were examined. We
      evidenced that middle-dosage administration mice had a lower inflammation, better
      body weight, and ameliorated mucosal morphology, accompanied by reduced
      intestinal permeability and tighter intestinal barrier. Fecal microbiota
      composition analysis in middle- or low-dosage mice revealed the Bifidobacterium
      count was increased and the coliform bacteria count was decreased, and increased
      in short-chain fatty acid levels. Unexpectedly, there was a risk that high-dosage
      mice increased intestinal permeability and imbalance of intestinal bacteria.
      Taken together, these data indicated a safe threshold for usage of MccJ25 in
      clinical practice. Such studies can effectively enhance the safety of various
      aspects such as food preservative and drug.

PMID- 30298741
TI  - Adsorption Thicknesses of Confined Pure and Mixing Fluids in Nanopores.
AB  - In this paper, adsorption thicknesses of confined pure and mixing fluids in
      nanopores are quantitatively determined and their influential factors are
      specifically evaluated. First, a new analytical formulation is developed
      thermodynamically to calculate the adsorption thicknesses. Second, a new
      generalized equation of state (EOS), which considers the confinement effect
      induced phenomena, is developed analytically for calculating the thermodynamic
      confined fluid phase behavior. Third, the modified model based on the generalized
      EOS and coupled with the parachor model is applied to calculate the vapor-liquid
      equilibrium (VLE) and fluid adsorptions for the pure CO2, alkanes of C1-C10, and
      two mixtures of CO2-C10H22 and CH4-C10H22 in nanopores. Finally, the following
      five important factors are studied to evaluate their effects on the adsorption
      thickness: temperature, pressure, pore radius, wall-effect distance, and feed gas
      to-liquid ratio (FGLR). The proposed modified EOS is found to be accurate for the
      VLE and adsorption isotherm calculations. The adsorption thicknesses of confined
      pure or mixing alkanes are increased with the increasing carbon number but
      decreased with the temperature increase. For the alkanes of C1-C10, the degree of
      temperature effect is strengthened with the carbon number increase. Moreover, the
      adsorption thicknesses are significantly decreased with the pore radius increase
      until rp = 50 nm, after which they have slight changes or are even constant at
      any pore radii. On the other hand, the wall-effect distance (deltap) increase
      causes the adsorption thickness to be linearly increased at deltap/ rp >= 0.02.
      In addition, the effects of the FGLR and pressure on the adsorption thicknesses
      at the nanoscale are found to be negligible.

PMID- 30298742
TI  - Absorption, Metabolism, and Pharmacokinetics Profiles of Norathyriol, an Aglycone
      of Mangiferin, in Rats by HPLC-MS/MS.
AB  - Norathyriol, an aglycone of mangiferin, is a bioactive tetrahydroxyxanthone
      present in mangosteen and many medicinal plants. However, the biological fate of
      norathyriol in vivo remains unclear. In this study, the absorption and metabolism
      of norathyriol in rats were evaluated through HPLC-MS/MS. Results showed that
      norathyriol was well absorbed, as indicated by its absolute bioavailability of
      30.4%. Besides, a total of 21 metabolites of norathyriol were identified in rats,
      including methylated, glucuronidated, sulfated and glycosylated conjugates, which
      suggested norathyriol underwent extensive phase II metabolism. Among those
      metabolites, 15 metabolites were also identified in hepatocytes incubated with
      norathyriol, indicating the presence of hepatic metabolism. Furthermore,
      glucuronide and sulfate conjugates, rather than their parent compound, were found
      to be the main forms existing in vivo after administration of norathyriol, as
      implicated by the great increase of exposure of norathyriol determined after
      hydrolysis with beta-glucuronidase and sulfatase. The information obtained from
      this study contributes to better understanding of the pharmacological mechanism
      of norathyriol.

PMID- 30298743
TI  - Pattern-based formulation: clinical case 5.
AB  - OBJECTIVE: To demonstrate how the Pattern-based Formulation can be used to
      integrate biological, psychological and sociocultural factors in constructing the
      case formulation in a patient who developed schizophrenia and post-psychotic
      depression. CONCLUSIONS: Three new patterns are introduced and used to construct
      a comprehensive case formulation. This expands the suite of patterns in the
      pattern-based method of psychiatric case formulation, and further demonstrates
      its broad utility as an educational resource in psychiatry training.

PMID- 30298744
TI  - Engaging older adults in discharge planning: case studies illuminating approaches
      adopted by family members that promote relational autonomy.
AB  - BACKGROUND: Discharge decisions have significant implications for older adults
      and their involved family members. Evidence of older adult and family members'
      engagement in discharge decision-making, however, varies widely. Some recent work
      shows assumed associations between ageing, diminished participation in healthcare
      decision-making and increased reliance on family members. Other research suggests
      that family members adopt strategies to promote older adults' participation in
      decision-making. Relational autonomy theory suggests that individuals have
      differing levels of autonomy and that individuals' agency can be supported (or
      marginalized) by others. PURPOSE: Using three case studies, we examine
      traditional and relational conceptions of autonomy and explore how relational
      approaches could inform healthcare practice. METHODS: Taking a critical feminist
      bioethics perspective, we present a secondary analysis of three microethnographic
      case studies focused on discharge planning with older adults in one Canadian
      inpatient rehabilitation setting. The data consist of observations of discharge
      planning family conferences and semi-structured interviews with older adults and
      family members. RESULTS: Tensions between older adults' wishes to return home and
      their diminished participation in discharge decisions, and family members'
      assumption of a primary role in discharge decision-making and their wish for the
      older adult to move to a supported setting were apparent. To reconcile these
      tensions, the older adults' family members in these cases employed strategies to
      promote older adults' participation in decision-making that were consistent with
      relational autonomy theory. CONCLUSION AND IMPLICATIONS FOR PRACTICE: The
      analysis suggests that older adults' participation in discharge decision-making
      processes could be better promoted through relational approaches. Implications
      for rehabilitation  * Adopting an approach guided by relational autonomy might
      better enable patients to participate in decision-making than would an approach
      guided by traditional conceptions of autonomy.  * Rehabilitation professionals
      could seek assistance from family members and guide them toward collaborative
      partnerships.  * A range of strategies may be employed to customize relational
      approaches to enhance autonomy:     * having several different conversations with
      patients to enable multiple chances to contribute knowledge and views; *
      involving family members or taking the time to explain information several
      different times and in diverse manners; * showing patients videos or photos of
      discharge locations; * exploring a breadth of potential discharge options; *
      accompanying patients to visit different options in person; and * getting
      patients in touch with individuals who have made similar choices.  * It is
      recognized that taking a relational approach might be time-consuming and that
      practice contexts may not be conducive to such practice.

PMID- 30298745
TI  - Working life trajectories with hearing impairment.
AB  - PURPOSE: The aim was to identify and explore factors, which facilitate or hinder
      work participation for people with hearing impairment. MATERIALS AND METHODS: In
      depth interviews with 21 hearing impaired individuals of 32-67 years of age with
      a present or recent vocational affiliation were conducted. The analysis was
      conducted using a grounded theory approach. RESULTS: The analysis resulted in a
      conceptual framework of working life trajectories evolving through three phases
      of acknowledgement of hearing loss impact: the pre-acknowledgement,
      acknowledgement, and post-acknowledgement phase. The phases were influenced by
      the qualities of three contexts: the personal, the workplace, and the service
      provider. The qualities of the contexts, together with the amount of time spent
      in a pre-acknowledgement phase, formed the trajectories towards continuation of
      work participation or towards a disconnection. Accumulated risk factors
      constituted increased likelihood of disconnecting trajectories, while accumulated
      facilitating factors supported sustainable trajectories. CONCLUSIONS: The results
      revealed a need for extended support at the workplaces, which includes the
      manager, colleagues, and professionals in the aim of preventing exhaustion and
      facilitate work participation among employees with hearing impairments. Joint
      action in facilitating communicative participation would share the responsibility
      for accommodation measures and broaden the room for manoeuver at the workplace.
      Implications for rehabilitation Fatigue prevention in employees with hearing loss
      needs to be addressed in occupational rehabilitation. Knowledge transfer on
      hearing loss implications needs to be included in aural rehabilitation.
      Occupational rehabilitation professionals and professionals targeting hearing
      impairments should enter into systematic, multidisciplinary follow-up at the
      worksite.

PMID- 30298746
TI  - Enhanced Effect of Tendon Stem/Progenitor Cells Combined With Tendon-Derived
      Decellularized Extracellular Matrix on Tendon Regeneration.
AB  - Decellularized extracellular matrices have been clinically used for tendon
      regeneration. However, only a few systematic studies have compared tendon
      stem/progenitor cells to mesenchymal stromal cells on the tendon-derived
      decellularized matrix. In the present study, we prepared extracellular matrix
      derived from porcine tendons and seeded with tendon stem/progenitor cells,
      embryonic stem cell-derived mesenchymal stromal cells or without stem cells. Then
      we implanted the mixture (composed of stem cells and scaffold) into the defect of
      a rat Achilles tendon. Next, 4 weeks post-surgery the regenerated tendon tissue
      was collected. Histological staining, immunohistochemistry, determination of
      collagen content, transmission electron microscopy, and biomechanical testing
      were performed to evaluate the tendon structure and biomechanical properties. Our
      study collectively demonstrated that decellularized extracellular matrix derived
      from porcine tendons significantly promoted the regeneration of injured tendons
      when combined with tendon stem/progenitor cells or embryonic stem cell
      mesenchymal stromal cells. Compared to embryonic stem cell-mesenchymal stromal
      cells, tendon stem/progenitor cells combined with decellularized matrix showed
      more improvement in the structural and biomechanical properties of regenerated
      tendons in vivo. These findings suggest a promising strategy for functional
      tendon tissue regeneration and further studies are warranted to develop a
      functional tendon tissue regeneration utilizing tendon stem/progenitor cells
      integrated with a tendon-derived decellularized matrix.

PMID- 30298747
TI  - Naive B-cell output in HIV-infected and HIV-uninfected children.
AB  - BACKGROUND: In this study, we aimed to quantify KREC (kappa-deleting
      recombination excision circles) levels and naive B-cell output in healthy HIV
      uninfected children, compared with HIV-infected South African children, before
      and after starting ART (anti-retroviral therapy). SETTING: Samples were acquired
      from a Child Wellness Clinic (n=288 HIV-uninfected South African children, 2
      weeks - 12 years) and the Children with HIV and Early Antiretroviral Therapy
      (CHER) trial (n=153 HIV-infected South African children, 7 weeks - 8 years).
      METHODS: Naive B-cell output was estimated using a mathematical model combining
      KREC levels to reflect B-cell emigration into the circulation, flow cytometry
      measures of naive un-switched B-cells to quantify total body naive B-cells, and
      their rates of proliferation using the intracellular marker Ki67. RESULTS: Naive
      B-cell output increases from birth to 1 year, followed by a decline and plateau
      into late childhood. HIV-infected children on or off ART had higher naive B-cell
      outputs than their uninfected counterparts (p=0.01 and p=0.04). CONCLUSIONS: This
      is the first study to present reference ranges for measurements of KRECs and
      naive B-cell output in healthy and HIV-infected children. Comparison between HIV
      uninfected healthy children and HIV-infected children suggest that HIV may
      increase naive B-cell output. Further work is required to fully understand the
      mechanisms involved and clinical value of measuring naive B-cell output in
      children.  .

PMID- 30298748
TI  - Beneficial Effects of Korean Red Ginseng in the Progression of Non-Alcoholic
      Steatohepatitis via FABP4 Modulation.
AB  - Korean red ginseng (KRG) is a traditional herbal medicine used to prevent several
      geriatric diseases due to its therapeutic effects on metabolic disorder,
      including type 2 diabetes and fatty liver disease. In this study, we investigated
      the effects of KRG on the progression of nonalcoholic steatohepatitis (NASH) in
      mice. NASH was induced by feeding a methionine- and choline-deficient high-fat or
      high-fat/high-sucrose diet for 6 or 13 weeks, respectively. Each diet group was
      also orally administered saline (group G0) or KRG extract (100, 200, or 400
      mg/kg/day; groups G1, G2, and G4, respectively). KRG showed anti-inflammatory and
      antifibrogenic effects in the diet-induced NASH models. Furthermore, the
      expression levels of lipid metabolism-related genes were markedly decreased with
      KRG treatment in both diet-induced NASH groups. We next confirmed the expression
      levels of FABP4 in the liver and its ability to regulate inflammation and/or
      oxidative stress. We observed decreased levels of FABP4 mRNA and protein in the
      KRG-treated groups indicating that KRG affects the pathogenesis of NASH-related
      inflammatory responses by modulating FABP4 expression. Results of in vitro
      experiments showed similar patterns in cells treated with KRG, indicating that
      KRG treatment regulates the expression of FABP4 and subsequently reduces NASH
      related inflammation. Our findings suggest a novel role of KRG in NASH-related
      inflammatory responses via modulation of FABP4 expression in the liver. KRG may
      be a safe alternative therapy to prevent NASH progression.

PMID- 30298749
TI  - The Most Commonly Treated Acupuncture Indications in the United States: A Cross
      Sectional Study.
AB  - Acupuncture has been a popular alternative medicine in the United States for
      several decades. Its therapeutic effects on pain have been validated by both
      basic and clinical researches, and it is currently emerging as a unique non
      pharmaceutical choice for pain against opioid crisis. However, the full spectrum
      of acupuncture indications remains unexplored. In this study, we conducted a
      cross-sectional survey among 419 acupuncturists nation-wide to investigate the
      top 10 and top 99 acupuncture indications in private clinics in the United
      States. We found the top 10 indications to be: lower back pain, depression,
      anxiety, headache, arthritis, allergies, general pain, female infertility,
      insomnia, neck pain and frozen shoulder. Among the top 99 indications, pain
      represents the largest category; and mental health management, especially for
      mood disorders, is in greatest demand. The following popular groups are: immune
      system dysfunctions, gastrointestinal diseases, gynecology and neurology. In
      addition, specialty index, commonality index, and the potential to become medical
      specialties were estimated for each indication. Demographic analysis suggests
      that China trained acupuncturists tend to have broader indication spectrums, but
      the top conditions treated are primarily decided by local needs. Also, gender,
      resident states, age and clinical experience all affect indication distributions.
      Our data for the first time outlines the profile of acupuncture treatable
      conditions in the US and is valuable for strategic planning in acupuncture
      training, healthcare administration and public education.

PMID- 30298750
TI  - Weight management services for an underserved population: a rapid review of the
      literature.
AB  - INTRODUCTION: Overweight and obesity (OW/OB) rates are increasing among Canadian
      children and youth, with rates currently affecting one-third of 5-17 year olds.
      OW/OB is associated with numerous physical and psychosocial consequences, which
      are compounded when a child has a pre-existing disability. This is concerning
      considering children with disabilities experience OW/OB at two to three times the
      rate of their typically developing peers. While the number of weight management
      programs have been increasing, they are generally designed to meet the needs of
      typically developing children and often exclude children with disabilities. This
      review identifies existing weight management programs for youth with
      disabilities, and examines their characteristics and outcomes. METHODS: A scoping
      review was conducted using rapid review principles. Three health and social
      science databases were searched using terms related to "disabilities", "obesity",
      and "weight management", limited to 2007-2017. Articles meeting the inclusion
      criteria were summarized and analyzed thematically. RESULTS: Five articles met
      inclusion criteria, and described four separate weight management programs. All
      included children and youth with intellectual disabilities, with one including
      children with physical disabilities. Programs had three traits in common: (1)
      utilizing inter/multidisciplinary teams; (2) using technology to deliver the
      program; and (3) engaging the family during the entire program. All articles
      reported that the programs reduced body mass index. CONCLUSION: The scarcity of
      programs designed to meet the unique needs of youth with disabilities is
      alarming. Although a robust evidence base is lacking, current research provides
      some directions into components that should be considered when designing future
      interventions. Implications for Rehabilitation    1.  Clinicians should be aware
      of the high prevalence of overweight and obesity and the resultant consequences
      in children with disabilities.    2.  The use of inter/multidisciplinary teams,
      technology, and family engagement all appear to be promising approaches to
      creating successful weight management programs: a.  Weight-management programs
      should utilize inter/multidisciplinary teams to consider physical, social and
      psychological aspects of weight and health, to allow treatment plans to encompass
      a wider range of suggestions and recommendations. b.  Health care providers
      should consider using technology as a platform to deliver weight-management
      programs and services and/or to directly track progress.    c.  Families are
      powerful agents of change, and should be consulted and involved in the delivery
      of weight-management programs.

PMID- 30298751
TI  - Adipose-derived Stem/Stromal Cells on Electrospun Fibrin Microfiber Bundles
      Enable Moderate Muscle Reconstruction in a Volumetric Muscle Loss Model.
AB  - Current treatment options for volumetric muscle loss (VML) are limited due to
      donor site morbidity, lack of donor tissue, and insufficient functional recovery.
      Tissue-engineered skeletal muscle grafts offer the potential to significantly
      improve functional outcomes. In this study, we assessed the potential pro
      myogenic effects of human adipose-derived stem cells (ASCs) seeded onto
      electrospun uniaxially aligned fibrin hydrogel microfiber bundles. Although both
      uninduced and 5-azacytidine-induced ASCs exhibited alignment, elongation, and
      diffuse muscle marker expression when grown on microfiber bundles for 2 months in
      vitro, both groups failed to fully recapitulate myotube characteristics. To
      assess the muscle regeneration potential of ASCs in vivo, ASC-seeded fibrin
      microfiber bundles were implanted in a robust murine VML defect model. Minimal
      fibrosis was observed surrounding implanted acellular hydrogel fibers at 2 and 4
      weeks, and fibers seeded with ASCs exhibited up to 4 times higher volume
      retention than acellular fibers. We observed increased numbers of cells positive
      for the regenerating muscle marker embryonic myosin and the mature muscle marker
      myosin heavy chain in ASC-seeded fibers compared with acellular fibers at 1 and 3
      months post-transplantation. Regenerating muscle cells were closely associated
      with ASC-derived cells and in some cases had potentially fused with them. These
      findings demonstrate that despite failing to undergo myogenesis in vitro, ASCs
      combined with electrospun fibrin microfibers moderately increased muscle
      reconstruction in vivo compared with acellular fibers following a severe VML
      defect.

PMID- 30298752
TI  - Deep Brain Stimulation for Amelioration of Cognitive Impairment in Neurological
      Disorders: Neurogenesis and Circuit Reanimation.
AB  - Acute (e.g., traumatic brain injury or stroke) and chronic (e.g., dementia or
      Parkinson's disease dementia) neurological disorders that involve cognitive
      impairment and dysfunctional neural circuits always lead to a dreadful and costly
      experience for patients and their families. The application of deep brain
      stimulation for the treatment of neuropsychiatric disorders has shown great
      potential to modulate pathological neural circuits and trigger endogenous
      neurogenesis. We summarize several important clinical and translational studies
      that utilize deep brain stimulation to improve cognition based on the
      potentiation of neural plasticity and neurogenesis. In addition, we discuss the
      neuroanatomy and cerebral circuits implicated in such studies as well as the
      potential mechanisms underlying therapeutic benefits.

PMID- 30298753
TI  - Implantation of the argus sling in a hard-to-treat patient group with urinary
      stress incontinence.
AB  - INTRODUCTION: Awareness of prostate cancer is growing in the Western population,
      and an increasing number of patients are being referred to prostate surgery. This
      is a significant contributor to male stress urinary incontinence (SUI).
      Implantation of an artificial sphincter (AUS) is considered the gold standard
      treatment of SUI. This study investigates the role of minimally invasive
      treatment with the Argus sling in a heterogenic hard-to-treat patient group.
      METHOD: The study was a retrospective follow-up study with patients as their own
      controls. Forty-one patients were enrolled and treated with the Argus sling.
      Patients enrolled had persisting SUI after prostate surgery for more than 12
      months, despite conservative treatment. The pre-operative daily usage of pads and
      the 24 hours urinary leakage were compared to the post-operative findings. The
      primary goal was to achieve complete continence or a reduction of more than 50%
      in pad usage or urinary leakage. RESULTS: In total, 71% of the 41 patients
      enrolled met our primary objective. Complete continence was obtained in 56%, and
      a reduction of 50% or more was obtained in an additional 15%. CONCLUSION: This
      study has reproduced continence rates seen in previous studies, but in the hard
      to-treat patients with urgency or formerly failed surgery, the continence rate
      was found to be inferior. The AUS has produced similar results and must still be
      considered the gold standard treatment of SUI, but the Argus sling is an
      alternative for patients who want a passive system or for patients not suitable
      for AUS.

PMID- 30298754
TI  - Survey of Australian psychiatrists' and psychiatry trainees' knowledge about and
      attitudes towards medicinal cannabinoids.
AB  - OBJECTIVE: To assess Australian psychiatrists' and psychiatry trainees' knowledge
      about and attitudes towards medicinal cannabinoids, given the recent relaxation
      of cannabinoid-prescribing laws in Australia. METHOD: All Australian members of
      the Royal Australian and New Zealand College of Psychiatrists were invited to
      participate in an anonymous, 64-item online questionnaire, through Royal
      Australian and New Zealand College of Psychiatrists' newsletters. The
      questionnaire ran for a 10-week period from March to May 2017. Participants were
      asked about their knowledge of the evidence for and against prescribing
      pharmaceutical-grade cannabidiol and tetrahydrocannabinol, and their concerns
      about prescribing medicinal cannabinoids. RESULTS: In total, 88 doctors responded
      to the survey, with 55 completing all items (23 psychiatrists, 32 trainees).
      Overall, 54% of respondents would prescribe medicinal cannabinoids if it was
      legal to do so. Participants believed there was evidence for the use of
      cannabidiol and tetrahydrocannabinol in treating childhood epilepsy, chronic
      pain, and nausea and vomiting. They were most concerned about medicinal
      cannabinoids leading to psychotic symptoms, addiction and dependence, apathy and
      recreational use. CONCLUSIONS: Our sample of Australian psychiatrists and
      trainees were aware of the main clinical indications for medicinal cannabinoids,
      but were poor at differentiating between the indications for cannabidiol versus
      tetrahydrocannabinol. Further education about medicinal cannabinoids appears
      necessary.

PMID- 30298755
TI  - Association between DNA methylation of the KITLG gene and cortisol levels under
      stress: a replication study.
AB  - A recent study reported for the first time, that DNA methylation of the KITLG
      gene mediates the association between childhood trauma and cortisol stress
      reactivity. Our study aimed to provide the first independent replication of these
      findings. ESPRIT is a prospective study of community-dwelling participants (age
      >= 65), randomly selected from the electoral rolls of the Montpellier district,
      in France. Clinical depression was assessed using the Mini-International
      Neuropsychiatric Interview (MINI, French version 5.00), and the Centre for
      Epidemiological Studies Depression Scale (CES-D). Experiences of childhood
      adversity were ascertained via a 25-item questionnaire. Morning, evening, and
      diurnal salivary cortisol was measured under basal and stress conditions and
      determined using direct radioimmunoassay analysis. DNA methylation of the KITLG
      gene was quantified in whole blood using the SEQUENOM MassARRAY EpiTYPER
      platform. A significant negative association was observed between KITLG DNA
      methylation and both morning cortisol (beta = -1.846 +/- 0.666, p = .007) and
      diurnal cortisol (area under curve [AUC]) (beta = -19.429 +/- 8.868, p = .031)
      under a stress condition. However, only the former association was significant
      after correcting for multiple testing. Further, this association remained after
      adjusting for age, sex, and depression status. No significant association was
      observed between childhood trauma and KITLG DNA methylation in this older
      population. This study provides support for an association between KITLG
      methylation and stress cortisol levels, suggesting that DNA methylation of this
      gene may play a role in the longer term regulation of the stress system. Lay
      summary   The significant negative association between KITLG DNA methylation and
      morning cortisol, measured under a stressful condition, suggests that individuals
      with higher KITLG methylation will secrete lower levels of cortisol whilst under
      stress.

PMID- 30298756
TI  - Corrigendum.

PMID- 30298757
TI  - Social anxiety and employment interviews: does nonverbal feedback differentially
      predict cortisol and performance?
AB  - BACKGROUND & OBJECTIVES: Interviewers often provide positive nonverbal feedback
      to reduce interviewees' anxiety. Socially anxious individuals typically harbor
      negative self-views discrepant with positive feedback. We examined whether
      nonverbal feedback and social anxiety jointly influence cortisol responses to,
      and performance during, interviews. DESIGN: An experimental between-subjects
      design randomly assigned participants to feedback condition. METHODS:
      Undergraduate students (N = 130) provided saliva and completed social anxiety,
      interview anxiety, and affective measures before a simulated interview. Following
      a standardized script, a confederate interviewer provided positive, ambiguous, or
      negative nonverbal feedback. Participants then provided saliva and completed self
      focused attention and self-awareness measures. Confederate interviewers and an
      external rater evaluated participants' anxiety displays, assertive behavior, and
      performance. RESULTS: Positive feedback decreased cortisol and improved
      performance for low social anxiety participants. Socially anxious participants
      exhibited higher cortisol but did not exhibit significant differences in
      performance after positive compared to negative feedback. CONCLUSIONS: Consistent
      with previous findings, positive feedback did not benefit socially anxious
      interviewees. Positive feedback increased physiological arousal relative to
      negative feedback but did not hinder performance among people high in social
      anxiety. These results provide novel information about the interactive influence
      of social anxiety and nonverbal interviewer feedback on arousal, self-focus, and
      interview performance.

PMID- 30298758
TI  - Managing the increasing diagnosis of papillary micro-cancer of thyroid.
AB  - There has been an increase in the incidence of thyroid cancer in the last decade,
      mainly due to the increase in imaging. A majority of the cases are for papillary
      cancers <1 cm. Mortality from thyroid cancer has stayed stable, thus, there is a
      large pool of papillary micro-cancer of thyroid in the general population without
      clinical significance. For these cancers a different approach is needed and
      active surveillance or less aggressive management should be offered as options.
      Controlled studies of minimally invasive procedures such as ethanol ablation are
      needed. If surgery is chosen, lobectomy alone should be adequate. Cases of occult
      papillary micro-cancer with local and distant metastases are very rare and should
      be managed according to the staging and risk category of the disease.

PMID- 30298759
TI  - Targeting pregnancy as a time to treat obesity.
AB  - Maternal obesity is recognized as one of the largest contributors to compromised
      health during pregnancy. Lifestyle interventions in obese pregnant women may be
      able to reduce gestational weight gain (GWG) but have shown limited success in
      improving pregnancy and neonatal outcomes. Lack of statistical power, poor
      compliance and inconsistency in inclusion BMI and setting across studies may be
      some of the reasons. Since pregestational BMI is the single most important
      predictor of obesity-related complications, the metabolic profile in the first
      trimester of pregnancy may play a very important role. Observational studies have
      shown that interpregnancy weight loss reduces the risk of macrosomia in a
      subsequent pregnancy. Future lifestyle randomized controlled trials should target
      the prepregnant state and examine the effect on maternal and neonatal outcomes.

PMID- 30298760
TI  - Bariatric surgery and diabetes remission: how far have we progressed?
AB  - Obesity and type 2 diabetes mellitus have been associated with higher morbidity
      and mortality. Bariatric surgery results in substantial and sustained weight loss
      in morbidly obese patients and improves obstructive sleep apnea. Furthermore,
      bariatric surgery improves diabetes control, hypertension, quality of life,
      stroke, myocardial infarction and reduces mortality. Interestingly, bariatric
      surgery induces high rates of short and long-term diabetes remission. While the
      exact mechanisms behind this are not completely understood, improved insulin
      action, beta-cell function and a complex interplay of hormones in the entero
      insular axis appear to play major roles. Insulin action improves proportionally
      to weight loss and it gets completely normalized especially after bilio
      pancreatic diversion. beta-Cell function also seems to improve after a variety of
      bariatric surgeries. Seemingly, baseline beta-cell function is able to predict
      future diabetes remission. This article will review the effectiveness of
      bariatric procedures on the remission and improvement of diabetes and its
      implicated mechanisms.

PMID- 30298761
TI  - Perinatal androgen exposure and adipose tissue programming: is there an impact on
      body weight fate?
AB  - Obesity is a major concern in public health because it is one of the main risk
      factors for the development of non-transmissible chronic diseases. The fact that
      there is a clear sex dimorphism in normal body fat distribution points out the
      role of sex steroids as key factors in the regulation and function of the adipose
      cell. Androgens affect adipogenesis and fat metabolism in the adipose tissue of
      males and females. Hormonal disorders during pregnancy may affect the fetal
      tissues, with long-term implications leading to the development of pathologies
      during adult life. Obesity and metabolic disease are among these. In this regard,
      animal models have demonstrated an abnormal fat distribution and modifications in
      the size and function of adipose cells in the female and male offspring of
      mothers exposed to androgen excess during pregnancy.

PMID- 30298762
TI  - Mass spectrometric analysis of steroids: all that glitters is not gold.
AB  - Steroid hormones are small molecules (MW around 300 Da) characterized by a large
      range of polarity and their analysis has always presented a serious challenge.
      Persistent problems with the specificity of conventional immunological methods
      are the cause of inconsistent results in the literature, a particularly
      problematic situation for healthcare decisions. At present, mass spectrometric
      methods have become the gold standard for accurate steroid profiling, and their
      advent will require the re-analysis of previously published data. However, it is
      a common misconception to consider the use of theses sophisticated technologies
      as a guarantee for accurate measures. Steroid analysis, especially in nervous
      tissues, indeed requires well-validated purification and separation steps before
      mass spectrometry, only then will mass spectrometric analysis be the absolute
      reference methodology.

PMID- 30298763
TI  - Romosozumab/CDP7851 for the treatment of osteoporosis.
AB  - Osteoporosis is an important worldwide health problem, conferring significant
      costs on healthcare. Current osteoporosis therapies are anti-resorptive and have
      proven anti-fracture efficacy, while there is a paucity of osteoanabolic
      therapies. Romosozumab is a humanized monoclonal antibody against sclerostin, an
      inhibitor of osteoblastic activity. Two-year follow-up data from initial clinical
      studies show rapid and robust increases in bone mineral density at all sites,
      except the wrist. Significant increases in bone formation markers have also been
      observed after administration of romosozumab. Notably, and unprecedented among
      any currently available therapy, this increase in bone formation is accompanied
      with control of bone resorption, allowing an enhanced anabolic potential compared
      with the only other currently available anabolic therapy, teriparatide.
      Romosozumab has been well tolerated in initial studies and its effects on BMD are
      augmented by follow-on anti-resorptive therapy. Ongoing Phase III studies will
      provide data regarding anti-fracture efficacy and comparisons with alendronate,
      as well as longer-term safety.

PMID- 30298764
TI  - Thyroid function in Down syndrome.
AB  - Down syndrome is the most commonly encountered human chromosomal disorder. Down
      syndrome is associated with thyroid dysfunction including: hypothyroidism, both
      congenital and acquired, and hyperthyroidism. A genetic predisposition and a
      propensity to acquire autoimmune disorders seem to be possible factors, though
      their causal relation remains unclear. The aim of the review is to describe what
      is currently known about the association between Down syndrome and thyroid
      dysfunction.

PMID- 30298765
TI  - Obesity and increased risk of esophageal adenocarcinoma.
AB  - There has been a substantial increase in the incidence of esophageal
      adenocarcinoma over the past 40 years. Meta-analyses of large prospective cohorts
      and population-based case-control studies demonstrate consistent associations
      between obesity and the development of adenocarcinoma of the esophagus and
      esophago-gastric junction, with an approximate doubling of risk of esophageal
      adenocarcinoma among patients who are obese, and an almost five-fold increased
      risk among those with BMI >40 kg/m2. The pathologic precursor, specialized
      intestinal metaplasia in Barrett's esophagus, is also associated with increased
      adiposity. Epidemiologic evidence suggests that this cancer risk is not solely
      due to increased gastro-esophageal reflux, and that adipose tissue itself, in
      particular visceral adipose, may fuel carcinogenesis through the production of
      adipokines, cytokines, growth factors, and increased inflammation. The robust
      epidemiologic evidence linking obesity with esophageal adenocarcinoma makes it an
      exemplar model for investigating the molecular mechanisms underpinning obesity
      associated malignant progression, which are discussed in this review.

PMID- 30298766
TI  - Outcome of complications in acromegaly patients after long-term disease
      remission.
AB  - Acromegaly patients suffer from pathologically high growth hormone (GH) and IGF-1
      levels that in 99% of cases is due to a GH-producing pituitary adenoma. During
      active disease, GH excess is associated with a number of pathological conditions,
      such as hypertension, hypertrophic cardiomyopathy, sleep apnea, arthropathy,
      vertebral fractures and insulin resistance. After adequate treatment in the form
      of transsphenoidal surgery, radiotherapy, medical treatment or by a combination
      of these treatment modalities, several comorbid conditions improve considerably.
      However, despite long-term biochemical disease control, the prevalence of late
      manifestations of GH excess is high and significantly impair quality of life. In
      addition, there is evidence that adequate treatment is not able to normalize
      mortality risk in these patients. In this review, we critically evaluate the long
      term consequences of acromegaly after treatment, focusing on comorbid conditions,
      quality of life and mortality. We also discuss ongoing challenges in the
      management of acromegaly patients.

PMID- 30298767
TI  - Barriers to care for patients with diabetes in Durham, North Carolina, why are we
      withholding life-sustaining medications from the patients who need them the most?
AB  - The diabetes epidemic and its complications disproportionately affect minorities
      and the poor. Medical treatments that can prevent or delay diabetes complications
      are widely available but poverty underlies much of why there are disparities in
      diabetes care and outcomes. Lack of access to care, food insecurity and inability
      to pay for medications prevents adherence to a medication and lifestyle regimen
      that can be life-sustaining. At the very least, US policies should be changed to
      provide life-sustaining medications that prevent costly complications to patients
      who cannot afford them. Adopting value-based insurance design would benefit
      patients with diabetes who cannot afford to pay for medications but would also
      reduce healthcare costs in the long run.

PMID- 30298768
TI  - Fcgamma-receptor polymorphisms associated with clinical symptoms in patients with
      immunoglobulin G subclass deficiency.
AB  - BACKGROUND: Immunoglobulin G subclass deficiencies (IgGsd) are associated with
      recurrent respiratory tract infections. Immunoglobulin substitution therapy may
      be needed to prevent chronic lung tissue damage but tools for identifying the
      patients that will benefit from this treatment are still insufficient. Some
      FcgammaR polymorphisms seem to predispose for an increased risk for infections.
      In this study we wanted to evaluate if the FcgammaR-profile differs between
      individuals with IgGsd and a control population. METHODS: Single nucleotide
      polymorphisms (SNPs) of FcgammaRIIa, FcgammaRIIIa and FcgammaRIIc in 36 IgGsd
      patients and 192 controls with similar sex and geographical distribution were
      analyzed by TaqMan allelic discrimination assay or Sanger sequencing. RESULTS: In
      the IgGsd-group, homozygous frequency for FcgammaRIIa-R/R131 (low-binding
      capacity isoform) was higher (p = .03) as well as for non-classical FcgammaRIIc
      ORF (p = .03) and classical FcgammaRIIc-ORF tended (p = .07) to be more common
      compared to the controls. There was no difference between the groups regarding
      FcgammaRIIIa. CONCLUSION: The gene for classical FcgammaRIIc-ORF tended to be
      more frequent in individuals with immunoglobulin G subclass deficiency and the
      genes for non-classical FcgammaRIIc-ORF as well as low-binding capacity receptor
      FcgammaRIIa-R/R131 were more frequent. Further studies on the FcgammaR
      polymorphisms may pave way for identifying individuals that will benefit from
      immunoglobulin substitution.

PMID- 30298769
TI  - Comparator clinical trials of surrogate endpoints with albiglutide are in
      HARMONY.
AB  - Evaluation of: Ahren B, Johnson SL, Stewart M et al. HARMONY 3: 104-Week
      randomized, double-blind, placebo- and active-controlled trial assessing the
      efficacy and safety of albiglutide compared with placebo, sitagliptin, and
      glimepiride in patients with type 3 diabetes taking metformin. Diabetes Care
      2014;37:2141-8 and Rosenstock J, Fonseca VA, Grass JL et al. Advancing basal
      insulin replacement in type 2 diabetes inadequately controlled with insulin
      glargine plus oral agents: a comparison of adding albiglutide, a weekly GLP-1
      receptor agonist, versus thrice-daily prandial insulin lispro. Diabetes Care
      2014;37:2317-25. Agonists of glucagon-like peptide-1 (GLP-1) receptors are used
      in the treatment of Type 2 diabetes. Albiglutide is a new long-acting GLP-1
      receptor agonist being developed for once weekly use. This is an evaluation of
      two clinical trials in the HARMONY clinical trials series. HARMONY 3 compares
      albiglutide with sitagliptin and glimepiride in subjects with Type 2 diabetes
      poorly controlled with metformin, and HARMONY 6 compares albiglutide with insulin
      lispro in subjects poorly controlled with slow/medium release preparations of
      insulin. Both studies showed that albiglutide lowered HbA1c and had advantages
      over its comparator drugs. However, questions remain about the safety of
      albiglutide. Albiglutide is not being used in subjects with a history of thyroid
      cancer because it is not known whether this is a rare adverse effect with
      albiglutide. Also, the safety of albiglutide in subjects with Type 2 diabetes and
      high cardiovascular risk is unknown.

PMID- 30298770
TI  - Novel insights on the treatment of hypercholesterolemia.
AB  - The diagnosis of dyslipidemia is increasing both in adulthood and in childhood
      because of not only the steadily increasing prevalence of obesity but also a rise
      of medical attention in detecting unfavorable genetic conditions in patients of
      all ages. Attempts in lifestyle changes are frequently failing and thus the
      pharmacological treatment of dyslipidemia is spreading in medical practice to
      reduce cardiovascular risk. In childhood, statins are authorized by 8 years of
      age. Nevertheless, data on their long-term safety and efficacy are still lacking,
      especially in ones with high cardiovascular risk and/or primary dyslipidemia such
      as homozygous familial hypercholesterolemia, considerable as a mainly exclusively
      pediatric disease. Thus, new pharmacological approaches are needed and have to be
      evaluated in all categories of patients. In this context, the update and the
      critical revision of new medications have become a new duty for scientists and
      clinicians.

PMID- 30298771
TI  - Clinically meaningful end points in the evolving treatment paradigm for
      radioactive iodine-refractory differentiated thyroid cancer.
AB  - Radioactive iodine (RAI) is often used post-operatively for treatment of
      differentiated thyroid cancer (DTC), but many patients develop RAI-refractory
      disease. Patients with RAI-refractory DTC may be asymptomatic and stable for long
      periods of time, so identifying tumors that are no longer likely to respond to
      RAI treatment and determining when to transition to systemic therapy are critical
      issues for optimal patient care. The purpose of this paper is to review and
      assess the end points used in studies of RAI-refractory DTC in relation to the
      issues facing clinicians in transitioning patients to systemic therapy. Our goals
      are to provide a framework to help evaluate whether study results are clinically
      meaningful in guiding treatment decisions and to make recommendations to better
      define these end points for RAI-refractory DTC.

PMID- 30298772
TI  - Nutraceuticals for the treatment of metabolic diseases: evidence from clinical
      practice.
AB  - The aim of this review is to describe some types of supplements that have been
      shown to be good co-adjuvants along with diet and drug treatment in improving
      insulin resistance and dyslipidemia. We can conclude that some nutraceuticals,
      such as l-carnitine, berberine, omega-3 polyunsaturated fatty acids, krill oil
      and red yeast rice, can be helpful in reducing hypercholesterolemia or insulin
      resistance, as reported in clinical trials. Nutraceuticals can be associated with
      conventional pharmacological treatments to achieve an improved lipid profile
      without increasing statin dosage. Similarly, although nutraceuticals cannot
      replace conventional antidiabetic treatments, they may be useful as an adjuvant
      to standard therapy, improving insulin resistance. However, not all
      nutraceuticals are the same and their natural origin does not mean that everyone
      can take them or that they cannot be dangerous; nutraceuticals should be used
      only under medical prescription and should be combined with a well-balanced diet.

PMID- 30298774
TI  - Growth hormone replacement in patients with a history of malignancy: a review of
      the literature and best practice for offering treatment.
AB  - Previous studies have implicated the growth hormone (GH)/IGF-I axis as an
      important mediator of cancer risk in humans and animals. Evidence supporting this
      notion is derived from animal studies, epidemiological observations, patients
      with acromegaly and from therapeutic manipulation of GH and IGF-I actions.
      Therefore, the use of GH therapy in patients with a history of malignancy raises
      hypothetical safety concerns. Reassuringly, GH therapy in childhood cancer
      survivors has not been confirmed to increase the cancer risk. Conversely, the
      risk of occurrence of a second neoplasm may be increased, with meningiomas being
      the most common tumor. In light of these findings, we propose considering GH
      therapy to be based on each individual's circumstance and commenced at least 2
      years after cancer remission is achieved with close monitoring during therapy.
      More long-term data are needed on the safety of GH replacement therapy in GH
      deficient adults with a history of malignancy.

PMID- 30298773
TI  - Predictive modeling for incident and prevalent diabetes risk evaluation.
AB  - With half of individuals with diabetes undiagnosed worldwide and a projected 55%
      increase of the population with diabetes by 2035, the identification of
      undiagnosed and high-risk individuals is imperative. Multivariable diabetes risk
      prediction models have gained popularity during the past two decades. These have
      been shown to predict incident or prevalent diabetes through a simple and
      affordable risk scoring system accurately. Their development requires cohort or
      cross-sectional type studies with a variable combination, number and definition
      of included risk factors, with their performance chiefly measured by
      discrimination and calibration. Models can be used in clinical and public health
      settings. However, the impact of their use on outcomes in real-world settings
      needs to be evaluated before widespread implementation.

PMID- 30298775
TI  - Thyroid surgery for treatment of Graves' disease complicated by ophthalmopathy: a
      comprehensive review.
AB  - Graves' disease (GD) is an autoimmune disorder in which antibodies directed
      against thyroid-stimulating hormone receptors leads to thyrotoxicosis. Graves'
      ophthalmopathy, a condition that occurs in up to half of GD patients, is a cause
      of significant morbidity and is potentially vision threatening. Three treatment
      options are equally effective for uncomplicated GD and these include thyroid
      surgery (thyroidectomy), radioactive iodine thyroid ablation and antithyroid
      drugs. However, recent practice surveys suggest that surgery is the least favored
      GD treatment. When GD is complicated by moderate-to-severe Graves'
      ophthalmopathy, antithyroid drugs and surgery are recommended by current
      guidelines, and again the preference for thyroid surgery in these cases has
      remained low. This report aims to review current published data regarding
      thyroidectomy as a treatment for GD, and in particular, we focus on the effects
      of thyroidectomy on Graves' ophthalmopathy development and progression.

PMID- 30298776
TI  - Therapeutic potential of miRNAs in diabetes mellitus.
AB  - miRNAs are major regulators of gene expression that are emerging as central
      players in the development of many human diseases, including diabetes mellitus.
      In fact, the manifestation of diabetes is associated with alterations in the
      miRNA profile in insulin-secreting cells, insulin target tissues and, in case of
      long-term diabetes complications, in many additional organs. Diabetes also
      results in changes in the profile of miRNAs detectable in blood and other body
      fluids. This has boosted an ever increasing interest in the use of circulating
      miRNAs as potential biomarkers to predict the development of diabetes and its
      devastating complications. Moreover, promising approaches to correct the level of
      selected miRNAs are emerging, permitting to envisage new therapeutic strategies
      to treat diabetes and its complications.

PMID- 30298777
TI  - Potential for dipeptidyl peptidase-4 inhibitor and sodium glucose cotransporter 2
      inhibitor single-pill combinations.
AB  - With prolonged duration of Type 2 diabetes mellitus, most patients need a
      combination of antihyperglycemic drugs to reach their target HbA1c. Evidence
      shows that single-pill combinations (SPCs) may increase patient satisfaction,
      adherence, and reduce overall health-care costs. Several SPCs containing
      metformin and another oral antidiabetic drug (OAD) are available on the market.
      Although well established in clinical practice, long-term durability and
      tolerability of traditional OADs can be inadequate. Dipeptidyl peptidase (DPP)-4
      inhibitors and sodium glucose cotransporter (SGLT) 2 inhibitors are two newer
      classes of OADs that are efficacious and are less likely to induce adverse
      effects such as gastrointestinal reactions, hypoglycemia and weight gain when
      compared with metformin, sulfonylureas, and thiazolidinediones. This article
      describes current efficacy and safety data of DPP-4/SGLT2 inhibitor combination
      therapy. Pharmacokinetics, mechanism-of-action based rationale for the
      combination and timing of the addition of a SPC to the treatment regimen are
      discussed.

PMID- 30298778
TI  - Phylogeography of Endangered Bitterling Acheilognathus melanogaster Endemic to
      Eastern Japan.
AB  - The bitterling Acheilognathus melanogaster is a critically endangered primary
      freshwater fish endemic to the Pacific side of eastern Japan. To elucidate A.
      melanogaster genetic structure, we investigated phylogeography in nine
      populations, using gene sequences of mitochondrial Cytochrome b (Cytb), as well
      as nuclear Rhodopsin (Rho) and glycosyltransferase (Glyt). We found four Cytb
      based geographical clusters unevenly divided between the northern and southern
      regions, with smaller groups in the south. Of the nuclear genes, Glyt did not
      show geographical differentiation, whereas Rho formed two clusters: one widely
      occurring and another restricted to central regions. Genetic diversity was
      generally higher in southern than in northern populations. Our results suggest
      that conservation of southern local populations is particularly important in
      maintaining the genetic diversity of this endangered fish.

PMID- 30298779
TI  - Genetic Diversity of MHC Class II DRB1 Exon 2 in the Red Fox (Vulpes vulpes) on
      Hokkaido, Japan.
AB  - To assess the genetic diversity of the red fox (Vulpes vulpes) population on
      Hokkaido Island, northern Japan, we examined genotypes of exon 2 of the major
      histocompatibility complex (MHC) class II DRB1 gene for 232 individuals and
      identified 17 novel alleles. The subpopulation in the Southern area was
      genetically differentiated from those in all other areas on Hokkaido, suggesting
      isolation in southern Hokkaido. In addition, the Southern subpopulation is lower
      in genetic diversity than the other subpopulations, possibly resulting from
      purifying selection and/or a recent bottleneck. The non-synonymous substitutions
      exceeded the synonymous substitutions for codons encoding antigen-binding sites
      (ABSs) in exon 2, indicating that the red fox DRB1 alleles have evolved under
      positive selection. In a Bayesian phylogenetic tree, although most of the DRB1
      alleles from the Hokkaido red fox were contained within a red fox-like canid
      (Vulpes) clade, some belonged to another canid clade. This means trans-species
      polymorphism maintained by balancing selection. Our results showed the local
      variability and the presence of selection on the MHC gene in this population,
      which contributes to the understanding of the historical background and the
      molecular evolution.

PMID- 30298780
TI  - A New Species of Sulcospira (Gastropoda: Pachychilidae) from Hunan, China.
AB  - A new species of pachychilid freshwater gastropod, Sulcospira hunanensis sp.
      nov., is described from Hunan Province, China, based on morphological and
      molecular evidence. The new species is distinguished from its congeners by a
      combination of characters, including elongated shell with eight to nine whorls,
      spiral whorls with ribs, and stomach with outer and inner crescentic pads not
      connected to each other. Sulcospira hunanensis sp. nov. is the first confirmed
      report of this genus from Hunan Province, China. It is anticipated that further
      species will be found in this region, which currently remain unknown.
      Furthermore, based on morphological and molecular evidence, this study is the
      first record of Sulcospira tonkiniana in Guangxi Zhuang Autonomous Region, China,
      with Sulcospira krempfi supported as a synonym of Sulcospira tonkiniana.

PMID- 30298781
TI  - Binucleation of Accessory Gland Lobe Contributes to Effective Ejection of Seminal
      Fluid in Drosophila melanogaster.
AB  - The adult male accessory gland in insects is an internal reproductive organ
      analogous to the mammalian prostate, and secretes various components in the
      seminal fluid. Products of the accessory gland in the fruit fly Drosophila
      melanogaster are known to control reproductive behaviors in mated females, such
      as food uptake, oviposition rate, and rejection of re-mating with other males,
      all of which increase male reproductive capacity. Production of larger amounts of
      accessory gland products is thus thought to result in higher male reproductive
      success. The epithelium of the Drosophila accessory gland lobe is composed of a
      unique population of binucleate cells. We previously predicted, based on
      measurements of cell size in mono/binucleate mosaic accessory glands, that
      binucleation results in a higher plasticity in cell shape, enabling more
      effective ejection of seminal fluid. However, the actual effect of binucleation
      on ejection of seminal fluid or reproductive capacity remained unclear, as we
      were unable to generate an organ with uniformly mononucleate cells. In the
      present study, we generated organs in which most of the epithelial cells are
      mononucleate by manipulating aurora B or fizzy-related to block binucleation.
      Mononucleation resulted in a less elastic accessory gland lobe, which decreased
      ejection volume and the oviposition of mated females; these effects were
      particularly pronounced over the long term. These results suggest that
      binucleation in accessory gland epithelial cells contributes to higher plasticity
      in the volume of this organ, and enhances male reproductive success through
      enabling ejection of larger amounts of seminal fluid.

PMID- 30298782
TI  - Ultraviolet Reflectance Structures of Peacock Feathers.
AB  - Male peacock (Pavo cristatus) tail feathers have an eyespot pattern with an
      inconspicuous black or dark blue center surrounded by brilliant, structural
      colors, such as blue, light brown, and yellow-green. Under ultraviolet A (UVA),
      the central part of the eyespot reflects UVA better than the surrounding parts.
      Herein, I examined various areas of eyespots on paraffin sections of feathers
      using an optical microscope, and characterized positional relationships between
      barbs and barbules. These analyses confirmed that barbules in the central part of
      the eyespot are in a horizontal position with respect to the barb, and that light
      transmission from the central part is less than that from the other parts. In
      addition, I compared microstructures of barbules in the central part of eyespot
      with those in surrounding areas using transmission electron microscope analysis.
      The melanin rods in the barbules reflecting yellow-green color comprise several
      ordered lattice structures. In contrast, melanin rods in the central part of the
      eyespot were only distributed in 1-3 layers on a part of the front side of the
      barbules. I also demonstrated that keratin structures of barbules are homogeneous
      in the central part of the eyespot, but have fibrous structures with many voids
      in the yellow-green parts. Collectively, the present observations suggest that
      feathers in the central part of the eyespot reflect UVA depending on the
      direction of irradiation, and these properties are governed by configurations of
      barbules relative to barbs, melanin rod distributions, and the presence of
      keratin structures with gaps.

PMID- 30298783
TI  - Reassessment of the Groundwater Amphipod Paramoera relicta Synonymizes the Genus
      Relictomoera with Paramoera (Crustacea: Amphipoda: Pontogeneiidae).
AB  - The systematic status of the stygobitic amphipod, Paramoera relicta Ueno, 1971,
      was revisited based on morphological examination of the paratypes, and molecular
      phylogenetic analyses using a newly collected specimen from its type locality.
      The paratypes clearly showed that this species does not possess the "sinusoid"
      antennal sinus in the head, which was erroneously described in the original
      description of this species; P. relicta is unquestionably classified within the
      genus Paramoera Miers, 1875 . Molecular phylogenetic trees obtained with nuclear
      histone H3 and mitochondrial 16S rRNA demonstrated that P. relicta clearly
      belongs to the clade consisting of Paramoera species. Since the genus
      Relictomoera Barnard and Karaman, 1982 was erected according to the "sinusoid"
      characteristic of its type species P. relicta, this genus is no longer valid, and
      should be treated as a junior subjective synonym of Paramoera. One of the
      paratypes of P. relicta is herein designated as a neotype for the species to
      clarify its taxonomic status and emend the morphological characteristics of this
      pontogeneiid amphipod.

PMID- 30298784
TI  - Microscopic and Submicroscopic Gradient Variation of Olfactory Systems among Six
      Sinocyclocheilus Species Living in Different Environments.
AB  - The fish genus Sinocyclocheilus contains many different species that inhabit
      diverse natural environments, such as surface water layer, cave, or intermediate.
      As a result of these different habitats there are some differences in their
      sensory systems. Microscopic and submicroscopic structures of olfactory systems
      in six representative species of Sinocyclocheilus were studied, including one
      surface-dwelling species (S. grahami), two intermediate species (S. jii and S.
      macrophthalmus) and three cave-dwelling species (S. brevibarbatus, S.
      anshuiensis, and S. tianlinensis). Due to adaptive evolution under extreme
      environmental conditions, cave-dwelling species have more developed olfactory
      systems. We observed that, compared with surface-dwelling species, the olfactory
      sac of the cave-dwelling Sinocyclocheilus species has the following
      characteristics: higher density of cilia, greater length of sensory cilia, many
      other special structures (micro-ridge, olfactory islet, rod cilia). These results
      reveal different levels of olfactory system development, consistent with the view
      that that cave-dwelling species have more developed olfactory systems than
      intermediate and surface-dwelling species.

PMID- 30298785
TI  - Does Nest Predation Influence Colony Movements of Saunders's Gulls
      (Saundersilarus saundersi) in a Reclaimed Land Area?
AB  - Some seabirds commonly use artificially reclaimed lands, which are frequently
      located next to mainland environments, for breeding. Nest predation risk caused
      by birds or mammals from the mainland has negative influence on fitness-related
      costs and distribution of seabirds. Here, we sought to link potential factors,
      specifically those related to nest predation and nest environment, with breeding
      performance and colony movements of the Saunders's gull (Saundersilarus
      saundersi), a vulnerable species, on a large reclaimed area (1350 ha) in Incheon
      in Republic of Korea. This reclaimed area has experienced rapid changes in
      communities of nest predators from the mainland and vegetation ranging from
      halophytes to terrestrial plants after reclamation. Additionally, changes in the
      surrounding of used nest sites were retrospectively examined to determine whether
      colony movement was reversible in this reclaimed area. Our results indicated that
      high nest predation in a previous year induced colony movements in a consecutive
      year while the breeding colony exhibited a gradual reduction in clutch size.
      However, such movement after high nest predation seemed to be irreversible due to
      ongoing habitat degradation caused by construction and vegetation alteration.
      This study highlights that high nest predation may exert strong pressure on
      breeding colonies of Saunders's gulls. It also has anthropogenic impacts, leading
      to continuous dispersal of colonies to new areas for this vulnerable seabird in a
      reclaimed land.

PMID- 30298786
TI  - Rediscovery after Almost 120 Years: Morphological and Genetic Evidence Supporting
      the Validity of Daphnia mitsukuri (Crustacea: Cladocera).
AB  - We examined the morphology of Daphnia individuals maintained in our laboratory
      for several years, originally collected in Lake Inbanuma, Chiba, Japan. We
      determined partial sequences of the mitochondrial cytochrome c oxidase subunit I
      and 12S rRNA genes from specimens in the cultured material. These animals are
      morphologically similar to D. obtusa Kurz, 1874 , but genetically distinct from
      this species. Our detailed observation shows that the morphological
      characteristics in the female and male individuals of our material are highly
      congruent with those of D. mitsukuri Ishikawa, 1896 , which has not been
      identified positively for more than 120 years since its original description,
      with its taxonomic identity having been questioned for almost 90 years. Based on
      our morphological and genetic data, we conclude that D. mitsukuri should be
      regarded as a taxonomically valid species. A search among public DNA sequence
      databases suggests D. mitsukuri is also distributed in China, although these
      Chinese sequences have been labeled as 'Daphnia pulex', representing
      misidentification.

PMID- 30298787
TI  - Molecular Phylogeny of the Family Capitellidae (Annelida).
AB  - Capitellids have emerged as monophyletic in most but not all recent molecular
      phylogenies, indicating that more extensive taxon sampling is necessary. In
      addition, monophyly of most or all capitellid genera was questionable, as some
      diagnostic characters vary ontogenetically within individuals. We tested the
      monophyly of Capitellidae and eight capitellid genera using phylogenetic analyses
      of combined 18S, 28S, H3, and COI gene sequences from 36 putative capitellid
      species. In our trees, Capitellidae formed a monophyletic sister group to
      Echiura, and Capitella was also monophyletic, separated by a long branch from
      other capitellids. Well-supported clades each containing representatives of
      different genera, or containing a subset of species within a genus, indicated
      that Barantolla, Heteromastus, and Notomastus are likely not monophyletic. We
      mapped three morphological characters traditionally used to define capitellid
      genera (head width relative to width of first segment, number of thoracic
      segments, and number of segments with capillary chaetae) onto our tree. While
      Capitella showed unique character states, states in the other genera were
      decidedly not phylogenetically informative. Morphology-based capitellid taxonomy
      will require a fine-scale reevaluation of character states and detection of new
      characters.

PMID- 30298788
TI  - Genetic Diversity among Clouded Salamanders (Hynobius nebulosus) in Shiga
      Prefecture.
AB  - The Japanese clouded salamander (Hynobius nebulosus) is a lentic-breeding species
      distributed throughout western Japan. Threats, such as habitat loss, have led to
      it being categorized as a vulnerable species. To explore the phylogeographic
      features and population differentiation among clouded salamanders in Shiga
      prefecture, we analyzed sequences of the mitochondrial cytochrome b gene. DNA
      samples were collected from 29 distinct breeding sites, and 53 cytochrome b
      haplotypes were identified. On the basis of comparison of the composition and
      frequency of haplotypes in each breeding site, salamanders in each habitat
      appeared to have distinct characteristics. Significant genetic differentiation
      was observed in 93.3% of possible pairs of habitats in Shiga prefecture, and
      67.7% of habitat pairs within the same locality were found to be significantly
      different. These results suggest that the salamanders' poor locomotion combined
      with topographic effects may have contributed to the diversity of locally
      distributed salamanders in Shiga. Phylogenetic analysis showed that haplotypes of
      H. nebulosus in Shiga can be divided into five groups (the Nagahama-Maibara
      group, Otsu group, Konan group 1, Konan group 2, and Takashima group), each with
      a distinct geographical distribution. Haplotypes of the Otsu group, however, were
      exceptionally widely distributed. The results of the present study will
      contribute to the future of H. nebulosus conservation management in Shiga.

PMID- 30298789
TI  - The way others move can influence what we choose.
AB  - Whether pointing at a menu item or rifling through a clothes rack, when we choose
      we often move. We investigated whether people's tendency to copy the movements of
      others could influence their choices. Participants saw pairs of pictures in
      private and indicated which one they preferred. They then entered a virtual art
      gallery and saw the same picture pairs in the presence of a virtual character.
      Having observed the virtual character point to indicate her preference with
      either a high or low movement trajectory, participants indicated their
      preference. There was either an anatomical (same movement, same choice) or
      spatial correspondence (same movement, different choice) between the
      participant's pictures and those of the virtual character. We found that
      participants copied the movement made by the virtual character rather than her
      action goal (i.e., her choice of picture). This resulted in a shift towards the
      virtual character's preferences in the anatomical condition but away from her
      preferences in the spatial condition. This effect was driven by the observation
      of the virtual character's high pointing movements. In a further experiment, we
      did not find any significant differences in imitation behaviour in autism,
      although autistic participants were less consistent in their choices. Our
      findings demonstrate that we are not only influenced by other's choices but also
      the types of movements others make to indicate those choices.

PMID- 30298790
TI  - BabA-mediated adherence of pediatric ulcerogenic H. pylori strains to gastric
      mucins at neutral and acidic pH.
AB  - Helicobacter pylori infection can result in non-ulcer dyspepsia (NUD), peptic
      ulcer disease (PUD), adenocarcinoma, and gastric lymphoma. H. pylori reside
      within the gastric mucus layer, mainly composed of mucins carrying an array of
      glycan structures that can serve as bacterial adhesion epitopes. The aim of the
      present study was to characterize the binding ability, adhesion modes, and growth
      of H. pylori strains from pediatric patients with NUD and PUD to gastric mucins.
      Our results showed an increased adhesion capacity of pediatric PUD H. pylori
      strains to human and rhesus monkey gastric mucins compared to the NUD strains
      both at neutral and acidic pH, regardless if the mucins were positive for Lewis b
      (Leb), Sialyl-Lewis x (SLex) or LacdiNAc. In addition to babA positive strains
      being more common among PUD associated strains, H. pylori babA positive strains
      bound more avidly to gastric mucins than NUD babA positive strains at acidic pH.
      Binding to Leb was higher among babA positive PUD H. pylori strains compared to
      NUD strains at neutral, but not acidic, pH. PUD derived babA-knockout mutants had
      attenuated binding to mucins and Leb at acidic and neutral pH, and to SLex and
      DNA at acidic pH. The results highlight the role of BabA-mediated adherence of
      pediatric ulcerogenic H. pylori strains, and points to a role for BabA in
      adhesion to charged structures at acidic pH, separate from its specific blood
      group binding activity.

PMID- 30298791
TI  - Analysis of Canadian multiple sclerosis patients does not support a role for
      FKBP6 in disease.

PMID- 30298792
TI  - Response to Vilarino-Guell et al.

PMID- 30298793
TI  - "If He's Abusing You . . . the Baby Is Going to Be Affected": HIV-Positive
      Pregnant Women's Experiences of Intimate Partner Violence.
AB  - Pregnancy represents a time of increased risk for intimate partner violence
      (IPV), and an HIV diagnosis further increases the vulnerability of this at-risk
      group. This study explores experiences of recent IPV using qualitative interviews
      with N = 12 HIV-positive pregnant women recruited from a clinical setting in
      South Africa, a location with a high global prevalence of IPV and HIV. Partner
      dynamics around IPV resulted in HIV shame and stigma and adversely affected
      engagement in HIV care and HIV treatment behaviors. The results highlight the
      challenges women face in navigating disclosure of both IPV and HIV, accessing
      necessary support, and engaging in both HIV-related and pregnancy-related care in
      the context of an abusive relationship.

PMID- 30298794
TI  - Identifying treatment responders using counterfactual modeling and potential
      outcomes.
AB  - Individualizing treatment according to patients' characteristics is central for
      personalized or precision medicine. There has been considerable recent research
      in developing statistical methods to determine optimal personalized treatment
      strategies by modeling the outcome of patients according to relevant covariates
      under each of the alternative treatments, and then relying on so-called predicted
      individual treatment effects. In this paper, we use potential outcomes and
      principal stratification frameworks and develop a multinomial model for left and
      right-censored data to estimate the probability that a patient is a responder
      given a set of baseline covariates. The model can apply to RCT or observational
      study data. This method is based on the monotonicity assumption, which implies
      that no patients would respond to the control treatment but not to the
      experimental one. We conduct a simulation study to evaluate the properties of the
      proposed estimation method. Results showed that the predictions of the
      probability of being a responder were well calibrated even if we observed
      variability and a small bias when many parameters were estimated. We finally
      applied the method to a cohort study on the selection of patients for additional
      radiotherapy after resection of a soft-tissue sarcoma.

PMID- 30298795
TI  - Beck Depression Inventory-II: Self-report or interview-based administrations show
      different results in older persons.
AB  - : ABSTRACTBeck Depression Inventory-II (BDI-II) is one of the most-used rating
      scales. It was developed as a tool administered either as a self-rating or
      interview-based, observer-rating scale. OBJECTIVE: The goal of this study is to
      compare BDI-II scores obtained with two standard methods of administration in
      community-based older persons. METHODS: BDI-II was administered at first in the
      self-rated version to a sample of 60 mentally healthy older persons (age 60-87
      years). Afterward, the interview-based administration was performed. ANALYSES: We
      compared the scores with nonparametric tests - Spearman's correlation coefficient
      and Wilcoxon Signed Ranks test. We also computed internal consistency. RESULTS:
      Self-rated BDI-II yielded significantly higher total score than interview (p <
      0.001, P = 88%). The correlation between total scores was moderate (rs = 0.46, p
      < 0.001). Item analysis revealed a larger decrease (lower scores) in the somatic
      items in the interview-based version. CONCLUSIONS: The two methods of
      administration result in different total score in healthy older persons.
      Therefore, interpretation of the scores should reflect the administration, which
      should be always specified in the studies.

PMID- 30298796
TI  - Intra-household double burden of malnutrition in a North African nutrition
      transition context: magnitude and associated factors of child anaemia with mother
      excess adiposity.
AB  - OBJECTIVE: In the Middle East and North Africa region, the nutrition transition
      has resulted in drastic increases in excess adiposity, particularly among women,
      while some types of undernutrition remain prevalent, especially among pre-school
      children. We assessed the magnitude, nature and associated factors of the within
      household co-occurrence of anaemia in children and excess adiposity in mothers.
      DESIGN: Cross-sectional survey using stratified two-stage random cluster sampling
      to survey households with women aged 20-49 years. BMI>=25.0 kg/m2 defined
      overweight and BMI>=30.0 kg/m2 obesity, while anaemia for children was defined as
      Hb<110 g/l. The associations between child anaemia and mother excess adiposity,
      and sociodemographic and lifestyle factors were estimated by multinomial
      regression. SETTING: Greater Tunis area, Tunisia, in 2009-2010. SUBJECTS:
      Children aged 6-59 months living with their 20-49-year-old mothers (437 child
      mother pairs). RESULTS: The most prevalent double burden of malnutrition in child
      mother pairs by far was the anaemic child and overweight mother (24.4 %; 95 % CI
      20.1, 29.3 %). A significant proportion of pairs were anaemic child and obese
      mother (14.4 %; 95 % CI 11.0, 18.5 %). The co-occurrence of anaemia in child and
      excess adiposity in mother was neither synergetic nor antagonistic (P=0.59 and
      0.40 for anaemia-overweight and anaemia-obesity, respectively). This double
      burden was more frequent among child-mother pairs with younger children, with
      mothers of higher parity and higher energy intakes. CONCLUSIONS: The high
      prevalence of anaemic child and overweight or obese mother requires special
      attention e.g. through interventions which simultaneously target both types of
      malnutrition within the same household.

PMID- 30298797
TI  - Who Is (Still) Looking After Mom and Dad? Few Improvements in Care Aides' Quality
      of-Work Life.
AB  - ABSTRACTUnregulated care aides provide most of the direct care to nursing home
      residents. We previously reported the first demographic profile of care aides in
      Western Canada through the Translating Research in Elder Care (TREC) longitudinal
      research program (2007-2022) in applied health services. Here we describe
      demographic, health, and work life characteristics of aides from 91 nursing homes
      in Western Canada. Demographics and work life varied significantly across health
      regions and facility owner-operator models. Our longitudinal cohort of aides from
      Alberta and Winnipeg had higher emotional exhaustion (a negative attribute),
      professional efficacy (a positive attribute), and experience of dementia-related
      responsive behaviours from residents. Overall, results indicate little
      improvement or worsening of care aide health and quality of work life. Coupled
      with limited provincial or national initiatives for workforce planning and
      training of these workers, this signals a long-term care system ill-prepared to
      care effectively for Canada's aging population.

PMID- 30298798
TI  - The tip of the iceberg: incompleteness of measles reporting during a large
      outbreak in The Netherlands in 2013-2014.
AB  - Measles is a notifiable disease, but not everyone infected seeks care, nor is
      every consultation reported. We estimated the completeness of reporting during a
      measles outbreak in The Netherlands in 2013-2014. Children below 15 years of age
      in a low vaccination coverage community (n = 3422) received a questionnaire to
      identify measles cases. Cases found in the survey were matched with the register
      of notifiable diseases to estimate the completeness of reporting. Second,
      completeness of reporting was assessed by comparing the number of susceptible
      individuals prior to the outbreak with the number of reported cases in the
      surveyed community and on a national level.We found 307 (15%) self-identified
      measles cases among 2077 returned questionnaires (61%), of which 27 could be
      matched to a case reported to the national register; completeness of reporting
      was 8.8%. Based on the number of susceptible individuals and number of reported
      cases in the surveyed community and on national level, the completeness of
      reporting was estimated to be 9.1% and 8.6%, respectively. Estimating the
      completeness of reporting gave almost identical estimates, which lends support to
      the credibility and validity of both approaches. The size of the 2013-2014
      outbreak approximated 31 400 measles infections.

PMID- 30298799
TI  - Bovine tuberculosis in working foxhounds: lessons learned from a complex public
      health investigation.
AB  - In 2017, Public Health England South East Health Protection Team (HPT) were
      involved in the management of an outbreak of Mycobacterium bovis (the causative
      agent of bovine tuberculosis) in a pack of working foxhounds. This paper
      summarises the actions taken by the team in managing the public health aspects of
      the outbreak, and lessons learned to improve the management of future potential
      outbreaks. A literature search was conducted to identify relevant publications on
      M. bovis. Clinical notes from the Public Health England (PHE) health protection
      database were reviewed and key points extracted. Animal and public health
      stakeholders involved in the management of the situation provided further
      evidence through unstructured interviews and personal communications. The PHE
      South East team initially provided 'inform and advise' letters to human contacts
      whilst awaiting laboratory confirmation to identify the infectious agent. Once M.
      bovis had been confirmed in the hounds, an in-depth risk assessment was
      conducted, and contacts were stratified in to risk pools. Eleven out of 20
      exposed persons with the greatest risk of exposure were recommended to attend TB
      screening and one tested positive, but had no evidence of active TB infection.
      The number of human contacts working with foxhound packs can be large and varied.
      HPTs should undertake a comprehensive risk assessment of all potential routes of
      exposure, involve all other relevant stakeholders from an early stage and
      undertake regular risk assessments. Current guidance should be revised to account
      for the unique risks to human health posed by exposure to infected working dogs.

PMID- 30298800
TI  - Association of cognitive impairment and grip strength trajectories with mortality
      among middle-aged and elderly adults.
AB  - : ABSTRACTBackground:This study investigates whether maintaining high levels of
      cognitive impairment and weak grip strength will predict a higher risk for
      mortality. METHODS: Data from the Korean Longitudinal Study of Aging (KLoSA) from
      2006 to 2014 was assessed using longitudinal data analysis and included 5,812
      research subjects. Our modeling approach jointly estimated multi-period
      trajectories of grip strength and cognitive impairment, and the primary analysis
      was based on Cox proportional hazards models. RESULTS: A four-class linear
      solution fit the data best in both cognitive impairment and grip strength based
      on the model fitness, respectively. The hazard ratio (HR) of mortality in group 1
      (consistently low) of cognitive impairment and of grip strength were 2.114 times
      higher (p-value 0.001) and 3.405 times higher (p-value <.0001) compared with
      group 3 (consistently high) and group 4 (consistently high), respectively.
      CONCLUSION: This study provides insightful scientific evidence into the
      specificity of longitudinal changes in grip strength and cognitive impairment on
      mortality. Our findings suggest that declined cognitive ability and weak grip
      strength are predictors of mortality in older Korean people.

PMID- 30298801
TI  - Case Report: Concurrent Sympatric Scrub Typhus and Japanese Spotted Fever in
      Japan.
AB  - Scrub typhus and Japanese spotted fever-both rickettsial diseases-are endemic and
      notifiable in Japan and may cause a fatal outcome without prompt treatment. Here
      we present the first case of a concurrent sympatric infection of both diseases
      with grade II evidence. A 67-year-old woman, after a single event of potential
      exposure to the pathogens, presented with a 12-day history of fever, pharyngeal
      pain, papulo-erythematous rash, and pronounced fatigue. Her erythematous rash was
      distributed on her trunk and extremities, palms, and soles and eventually
      progressed to purpura. Fever persisted until doxycycline was administered on day
      12. A significant > 4-fold increase in IgG and IgM titers against multiple
      serotypes of Orientia tsutsugamushi and Rickettsia japonica were revealed by
      indirect immunoperoxidase assays. These clinical and serological data, even in
      the absence of molecular or isolation evidence, provided grade II evidence that
      this was a concurrent infection of sympatric scrub typhus and Japanese spotted
      fever.

PMID- 30298802
TI  - Soil-Transmitted Helminth Infections and Anemia in Schoolchildren from Corn
      Island Archipelago (RAAS, Nicaragua).
AB  - The prevalence and intensity of soil-transmitted helminth (STH) infections in
      schoolchildren from Corn Islands (Nicaragua) were examined to detect mono- or
      poly-STH infected children, measuring different intensity levels, and to
      elucidate measurably increased odds of being anemic. A total of 341 stool samples
      provided by 2- to 15-year-old children were examined using a concentration
      technique and a Kato-Katz slide. Intensity of infection was expressed as eggs per
      gram (epg) of feces to classify light, moderate, or heavy intensity infection. A
      finger-prick blood sample was obtained from each student in the field. Soil
      transmitted helminth prevalence was 54.3%, with Trichuris trichiura as the most
      prevalent species (48.9%). The combination T. trichiura/Ascaris lumbricoides
      (12.6%) was the most common. When T. trichiura or A. lumbricoides appeared as a
      single infection, light or moderate intensity infections were seen, whereas when
      multiple species were identified, heavy infections were present. Anemia was
      detected in those with any kind of STH infection (42.7%), with statistically
      significant differences (P = 0.004) when compared with uninfected individuals
      (28.2%). Polyparasite infection with one parasite species at moderate intensity
      and the other parasite species at light intensity or absent was found to be a
      significant factor for the odds of being anemic (odds ratio = 2.07). The present
      study reveals a high level of STH transmission requiring a deworming control
      program in Corn Islands and pointing to the need of improving the education and
      sanitary conditions of the population to avoid environmental contamination and
      reinfection.

PMID- 30298803
TI  - A Low-Cost, Community Knowledge Approach to Estimate Maternal and Jaundice
      Associated Mortality in Rural Bangladesh.
AB  - In the absence of a civil registration system, a house-to-house survey is often
      used to estimate cause-specific mortality in low- and middle-income countries.
      However, house-to-house surveys are resource and time intensive. We applied a low
      cost community knowledge approach to identify maternal deaths from any cause and
      jaundice-associated deaths among persons aged >= 14 years, and stillbirths and
      neonatal deaths in mothers with jaundice during pregnancy in five rural
      communities in Bangladesh. We estimated the method's sensitivity and cost savings
      compared with a house-to-house survey. In the five communities with a total of
      125,570 population, we identified 13 maternal deaths, 60 deaths among persons
      aged >= 14 years associated with jaundice, five neonatal deaths, and four
      stillbirths born to a mother with jaundice during pregnancy over the 3-year
      period before the survey using the community knowledge approach. The sensitivity
      of community knowledge method in identifying target deaths ranged from 80% for
      neonatal deaths to 100% for stillbirths and maternal deaths. The community
      knowledge approach required 36% of the staff time to undertake compared with the
      house-to-house survey. The community knowledge approach was less expensive but
      highly sensitive in identifying maternal and jaundice-associated mortality, as
      well as all-cause adult mortality in rural settings in Bangladesh. This method
      can be applied in rural settings of other low- and middle-income countries and,
      in conjunction with hospital-based hepatitis diagnoses, used to monitor the
      impact of programs to reduce the burden of cause-specific hepatitis mortality, a
      current World Health Organization priority.

PMID- 30298804
TI  - Taking Sharper Pictures of Malaria with CAMERAs: Combined Antibodies to Measure
      Exposure Recency Assays.
AB  - Antibodies directed against malaria parasites are easy and inexpensive to measure
      but remain an underused surveillance tool because of a lack of consensus on what
      to measure and how to interpret results. High-throughput screening of antibodies
      from well-characterized cohorts offers a means to substantially improve existing
      assays by rationally choosing the most informative sets of responses and
      analytical methods. Recent data suggest that high-resolution information on
      malaria exposure can be obtained from a small number of samples by measuring a
      handful of properly chosen antibody responses. In this review, we discuss how
      standardized multi-antibody assays can be developed and efficiently integrated
      into existing surveillance activities, with potential to greatly augment the
      breadth and quality of information available to direct and monitor malaria
      control and elimination efforts.

PMID- 30298805
TI  - Entamoeba histolytica: Quantitative Proteomics Analysis Reveals Putative
      Virulence-Associated Differentially Abundant Membrane Proteins.
AB  - Entamoeba histolytica is a protozoan parasite that causes amebiasis and poses a
      significant health risk for populations in endemic areas. The molecular
      mechanisms involved in the pathogenesis and regulation of the parasite are not
      well characterized. We aimed to identify and quantify the differentially abundant
      membrane proteins by comparing the membrane proteins of virulent and avirulent
      variants of E. histolytica HM-1:IMSS, and to investigate the potential
      associations among the differentially abundant membrane proteins. We performed
      quantitative proteomics analysis using isobaric tags for relative and absolute
      quantitation labeling, in combination with two mass spectrometry instruments,
      that is, nano-liquid chromatography (nanoLC)-MALDI-MS/MS and nanoLC-electrospray
      ionization tandem mass spectrometry. Overall, 37 membrane proteins were found to
      be differentially abundant, whereby 19 and 18 membrane proteins of the virulent
      variant of E. histolytica increased and decreased in abundance, respectively.
      Proteins that were differentially abundant include Rho family GTPase,
      calreticulin, a 70-kDa heat shock protein, and hypothetical proteins. Analysis by
      Protein ANalysis THrough Evolutionary Relationships DB revealed that the
      differentially abundant membrane proteins were mainly involved in catalytic
      activities (29.7%) and metabolic processes (32.4%). Differentially abundant
      membrane proteins that were found to be involved mainly in the catalytic
      activities and the metabolic processes were highlighted together with their
      putative roles in relation to the virulence. Further investigations should be
      performed to elucidate the roles of these proteins in E. histolytica
      pathogenesis.

PMID- 30298806
TI  - Hymenolepis nana-An Emerging Intestinal Parasite Associated with Anemia in School
      Children from the Bolivian Chaco.
AB  - Tropical anemia can have multiple causes, whether socioeconomic, dietary, or
      infectious. In the Bolivian Chaco, soil-transmitted helminthiases (STH), malaria,
      and Chagas disease are potential infectious causes of anemia among school-aged
      children (SAC). Following years of preventive chemotherapy with mebendazole, the
      prevalence of STH among SAC living in that area is now negligible, whereas
      protozoan infections are still highly prevalent (81%); Hymenolepis nana is the
      most frequent intestinal helminth (~13%). We present results of hemoglobin (Hb)
      assessment and the association between parasitic infections and Hb levels of that
      SAC population. Overall, 511 SAC (girls:boys ratio 1:1, mean age 9.4 years [95%
      confidence interval {CI}: 9.3-9.5]) had Hb levels measured by using a portable Hb
      system HB 301+ (HemoCue1 AB; Angelhome, Sweden). The prevalence of anemia was 23%
      (117/511), with mean and median Hb level = 12.2 g/dL (95% CI: 12.1-12.3; range
      9.2-15.4 g/dL). By multivariate analysis, H. nana infection was associated with
      an increased risk of anemia (odds ratio 2.9, 95% CI: 1.5-5.7, P = 0.002). Two
      samples (0.5%) were positive for Trypanosoma cruzi and none for Plasmodium spp.
      by polymerase chain reaction of the 439 children tested. Anemia is still a
      concern among SAC living in the Bolivian Chaco. Our findings call for a greater
      attention to fecal-oral emerging pathogens, such as H. nana, and highlight the
      importance of water, sanitation, and hygiene improvements for disadvantaged
      population such as those living in the Bolivian Chaco.

PMID- 30298807
TI  - Hepatitis B Infection among Parturient in Peri-Urban Ghana.
AB  - Global evidence suggests that hepatitis B viral (HBV) infection is endemic in
      Africa and perinatal transmission remains one of the most important modes of HBV
      transmission in this area. This cross-sectional survey examined the
      seroprevalence and knowledge of hepatitis B among pregnant women attending
      antenatal clinic (ANC) in a mission hospital in Ghana. Systematic sampling
      technique was used to recruit 196 pregnant women. The level of statistical
      significance was set at 0.05 alpha level. The hepatitis B prevalence estimate
      (hepatitis B surface antigen) was 10.2% (N = 20) and the entirety of the
      participants were aware of HBV infection. Majority cited media (radio) as their
      main source of information. Approximately 86% of the participants (N = 168)
      associated HBV infection with a curse and 88.8% (N = 174) indicated witches and
      wizards as possible causes of the infection. Those with higher level of school
      education had high hepatitis B knowledge score (P < 0.01). Implementation of a
      health education program on the route of hepatitis B transmission is required in
      the study setting. Also, inclusion of hepatitis B education as part of ANC
      activities will enable HBV-positive pregnant women to appreciate the need for
      hepatitis B vaccination of their newborns at birth.

PMID- 30298808
TI  - Individual and Spatial Risk of Dengue Virus Infection in Puerto Maldonado, Peru.
AB  - Dengue virus (DENV) affects more than 100 countries worldwide. Dengue virus
      infection has been increasing in the southern Peruvian Amazon city of Puerto
      Maldonado since 2000. We designed this study to describe the prevalence of past
      DENV infection and to evaluate risk factors. In 2012, we conducted a cross
      sectional serosurvey and administered a knowledge, attitudes, and practices (KAP)
      questionnaire to members of randomly selected households. Sera were screened for
      antibodies to DENV by ELISA and confirmed by plaque reduction neutralization
      test. We created indices for KAP (KAPi). We used SaTScan to detect clustering and
      created a multivariate model introducing the distance of households to potential
      vector and infection sources. A total of 505 participants from 307 households
      provided a blood sample and completed a questionnaire. Fifty-four percent of
      participants (95% CI: 49.6; 58.5) had neutralizing antibodies to DENV. Higher
      values of KAPi were positively associated with having DENV antibodies in the
      multivariate analysis (odds ratio [ORII]: 1.6, 95% CI: 0.6, 2.4; ORIII: 2.7, 95%
      CI: 1.3, 5.5; and ORIV: 2.4, 95% CI: 1.2, 5.0). Older groups had lower chances of
      having been exposed to DENV than younger people (OR20-30: 0.5, 95% CI: 0.2, 0.8;
      OR31-45: 0.5, 95% CI: 0.3, 0.9; and OR>45: 0.6, 95% CI: 0.3, 1.3). Multivariate
      data analysis from the 270 households with location information showed male
      gender to have lower risk of past DENV infection (OR: 0.6, 95% CI: 0.4, 0.9). We
      conclude that risk of DENV infection in Puerto Maldonado is related to gender,
      age of the population, and location.

PMID- 30298809
TI  - Alternate Anti-Leprosy Regimen for Multidrug Therapy Refractory Leprosy: A
      Retrospective Study from a Tertiary Care Center in North India.
AB  - A subset of multibacillary (MB) leprosy patients manifest with clinical
      "nonresponsiveness" to the fixed-duration, World Health Organization multidrug
      therapy MB regimen (WHO-MDT-MBR). The aim of this retrospective study was to
      assess the effectiveness and safety of alternate anti-leprosy therapy (ALT) in
      such patients. This is an analysis of patients' records, registered in the
      leprosy clinic of our institute over a period of 6 years (2010-2015). The
      criteria for inadequate response/nonresponsiveness to treatment were as follows:
      1) persistent/new lesions after completing >= 12 months of WHO-MDT-MBR (isolated
      reactions were ruled out histopathologically) and 2) persistent
      positive/increasing value of the morphological index (MI) and a 2 log increase in
      the bacteriological index (BI) after >= 12 months of WHO-MDT-MBR. Such cases were
      treated with ALT consisting of minocycline, clofazimine, and ofloxacin (24
      months). Of 556 patients registered during the study period, 40.3% (224) were
      slit-skin smear (SSS) positive and 59.7% (332) were SSS negative. Of all, 35
      patients (6.3%) satisfied the criteria for clinical nonresponsiveness. Of 224 SSS
      positive patients, these 35 patients amounted to 15.6%. The mean BI and MI of
      these patients after completion of >= 12 months of WHO-MDT-MBR were 5.3 +/- 0.6
      and 14 +/- 6.8%, respectively. After 6 months of treatment with ALT, MI became
      negative (0) in all these patients. After completion of ALT, the mean BI and MI
      became 1.7 +/- 0.7 and 0%, respectively (P < 0.0001). There were 16 patients with
      corticosteroid-dependent recurrent/chronic erythema nodosum leprosum, who had
      excellent response with significant reduction in the number of reactional
      episodes and mean dose of prednisolone required (P < 0.0001). No serious adverse
      effects were noted. We conclude that ALT is safe and effective in the management
      of MB leprosy patients who are nonresponsive to 12 months of WHO-MDT-MBR.

PMID- 30298810
TI  - Antibodies in Melioidosis: The Role of the Indirect Hemagglutination Assay in
      Evaluating Patients and Exposed Populations.
AB  - Melioidosis is a major neglected tropical disease with high mortality, caused by
      the Gram-negative bacterium Burkholderia pseudomallei (Bp). Microbiological
      culture remains the gold standard for diagnosis, but a simpler and more readily
      available test such as an antibody assay is highly desirable. In this study, we
      conducted a serological survey of blood donors (n = 1,060) and adult melioidosis
      patients (n = 200) in northeast Thailand to measure the antibody response to Bp
      using the indirect hemagglutination assay (IHA). We found that 38% of healthy
      adults (aged 17-59 years) have seropositivity (IHA titer >= 1:80). The
      seropositivity in healthy blood donors was associated with having a declared
      occupation of rice farmer and with residence in a nonurban area, but not with
      gender or age. In the melioidosis cohort, the seropositivity rate was higher in
      adult patients aged between 18 and 45 years (90%, 37/41) compared with those aged
      >= 45 years (68%, 108/159, P = 0.004). The seropositivity rate was significantly
      higher in people with diabetes (P = 0.008). Seropositivity was associated with
      decreased mortality on univariable analysis (P = 0.005), but not on multivariable
      analysis when adjusted for age, diabetes status, preexisting renal disease, and
      neutrophil count. This study confirms the presence of high background antibodies
      in an endemic region and demonstrates the limitations of using IHA during acute
      melioidosis in this population.

PMID- 30298811
TI  - Enteric Fever in Cambodia: Community Perceptions and Practices Concerning Disease
      Transmission and Treatment.
AB  - Enteric fever is a systemic bacterial infection in humans that is endemic in
      Cambodia and for which antibiotic resistance is increasingly reported. To guide
      public health programs, this qualitative study sought to explore community
      perceptions on transmission and treatment. Participant observation was carried
      out in hospital settings, pharmacies, and at a community level in Phnom Penh. In
      depth interviews 39 and one focus group discussion were carried out with blood
      culture-confirmed enteric fever patients and purposively selected key informants.
      Informants were theoretically sampled based on initial themes identified using
      abductive analysis. Nvivo 11 was used for thematic coding. An urgent need to
      address health literacy concerning the transmission of enteric fever was
      identified, as lay informants did not link the disease and its symptoms to
      bacterial contamination of foods and drinks but rather to foods considered "bad"
      following humoral illness interpretations. As a result, lay informants considered
      recurrence of enteric fever preventable with appropriate dietary restrictions and
      Khmer traditional medicines. This study also reveals pluralistic health-care
      seeking behavior. For initial and mild symptoms, patients preferred home
      treatment or traditional healing practices; limited household finances delayed
      treatment seeking. When symptoms persisted, patients first visited drug outlets
      or private practitioners, where they received a mix of nonessential medicines and
      one or more antibiotics often without prescription or confirmation of diagnosis.
      Inappropriate use of antibiotics was common and was related to diagnostic
      uncertainty and limited finances, factors which should be addressed during future
      efforts to improve the uptake of appropriate diagnostics and treatment of enteric
      fever.

PMID- 30298812
TI  - Visceral Leishmaniasis in the Muzaffapur Demographic Surveillance Site: A
      Spatiotemporal Analysis.
AB  - In the Indian subcontinent, visceral leishmaniasis (VL) has a strongly clustered
      distribution. The "index case approach" is promoted both for active case finding
      and indoor residual spraying (IRS). Uncertainty exists about the optimal radius.
      Buffer zones of 50-75 m around incident cases have been suggested for active case
      finding, for IRS the recommendation is to cover a radius of 500 m. Our aim was to
      establish optimal target areas both for IRS and for (re)active case finding. We
      plotted incident VL cases on a map per 6-month period (January-June or July
      December) and drew buffers of 0 (same household), 50, 75, 100, 200, 300, 400, and
      500 m around these cases. We then recorded total population and numbers of VL
      cases diagnosed over the next 6-month period in each of these buffers and beyond.
      We calculated incidence rate ratios (IRRs) using the population at more than 500
      m from any case as reference category. There was a very strong degree of spatial
      clustering of VL with IRRs ranging from 45.2 (23.8-85.6) for those living in the
      same households to 14.6 (10.1-21.2) for those living within 75 m of a case
      diagnosed, during the previous period. Up to 500 m the IRR was still five times
      higher than that of the reference category. Our findings corroborate the
      rationale of screening not just household contacts but also those living within a
      perimeter of 50-75 m from an index case. For IRS, covering a perimeter of 500 m,
      appears to be a rational choice.

PMID- 30298813
TI  - Leptospirosis in French Historical Medical Literature: Weil's Disease or Kelsch's
      Disease?
AB  - Early names for leptospirosis often indicate occupational or environmental
      exposure. Leptospirosis is hard to identify in the tropical setting because of co
      circulating diseases. This is not the case in the temperate setting, such as
      Europe, where the few differential diagnoses at the time are malaria, typhoid,
      and viral hepatitis. Leptospirosis presumably caused community epidemics in
      Europe before 1900 and military epidemiologists carefully documented outbreaks in
      "constrained settings." Achille Kelsch (1841-1911) synthesized available military
      data and epidemiological perspectives to define "epidemic jaundice" as a
      nosological continuum, caused by an infectious agent found in muds and water. He
      viewed Weil's disease as being only one form of that now well-identified disease
      continuum. The causative pathogen and epidemiological determinants were
      identified years later. The role of soils and muds as intermediate reservoirs, as
      suggested by Kelsch, deserves further investigation.

PMID- 30298814
TI  - Aboard the Good Ship Verona.

PMID- 30298817
TI  - Anti-inflammatory effects of olive-derived hydroxytyrosol on lipopolysaccharide
      induced inflammation in RAW264.7 cells.
AB  - The control of inflammation, which arises from complex biological responses to
      harmful stimuli, is an important determinant of both clinical outcomes and
      patient comfort. However, the side effects of many current therapies such as non
      steroidal anti-inflammatory drugs mean that new safe treatments are required. We
      previously reported that 12.5 MUg/ml hydroxytyrosol (HT) suppressed gene
      expression of the inducible nitric oxide (NO) synthase (iNOS) isoform and NO
      production, in mouse peritoneal macrophages treated with lipopolysaccharide
      (LPS), where nuclear factor-kappaB (NF-kappaB) gene expression was not altered.
      The present study evaluated the anti-inflammatory effects of various
      concentrations of HT in LPS-induced RAW264.7 mouse macrophages. HT suppressed NF
      kappaB signaling and downregulated LPS-mediated expression of iNOS,
      cyclooxygenase-2, tumor necrosis factor alpha, and interleukin-1beta at 12.5
      MUg/ml, resulting in reduced production of NO and prostaglandin E2. At lower
      concentrations, HT seemed to act via another signaling pathway to regulate the
      inflammatory response. In contrast, HT did not suppress LPS-induced expression of
      phosphorylated p44/42 mitogen-activated protein kinase. This study showed that HT
      had anti-inflammatory effects on LPS-stimulated RAW264.7 cells. HT is already
      available as a nutritional supplement and no toxic effects have been reported.
      Hence, HT represents a potential novel anti-inflammatory agent.

PMID- 30298818
TI  - Highly Sensitive Voltammetric Sensor Using Carbon Nanotube and Ionic Liquid
      Composite Electrode for Xylazine Hydrochloride.

PMID- 30298819
TI  - A Novel Gold Nanoprobe for Simple Electrochemiluminescence Determination of
      Prostate-specific Antigen Based on Peptide Cleavage Reaction.

PMID- 30298816
TI  - Spatiotemporal mosaic self-patterning of pluripotent stem cells using CRISPR
      interference.
AB  - Morphogenesis involves interactions of asymmetric cell populations to form
      complex multicellular patterns and structures comprised of distinct cell types.
      However, current methods to model morphogenic events lack control over cell-type
      co-emergence and offer little capability to selectively perturb specific cell
      subpopulations. Our in vitro system interrogates cell-cell interactions and
      multicellular organization within human induced pluripotent stem cell (hiPSC)
      colonies. We examined effects of induced mosaic knockdown of molecular regulators
      of cortical tension (ROCK1) and cell-cell adhesion (CDH1) with CRISPR
      interference. Mosaic knockdown of ROCK1 or CDH1 resulted in differential
      patterning within hiPSC colonies due to cellular self-organization, while
      retaining an epithelial pluripotent phenotype. Knockdown induction stimulates a
      transient wave of differential gene expression within the mixed populations that
      stabilized in coordination with observed self-organization. Mosaic patterning
      enables genetic interrogation of emergent multicellular properties, which can
      facilitate better understanding of the molecular pathways that regulate symmetry
      breaking during morphogenesis.

PMID- 30298815
TI  - Ancient mechanisms for the evolution of the bicoid homeodomain's function in fly
      development.
AB  - The ancient mechanisms that caused developmental gene regulatory networks to
      diversify among distantly related taxa are not well understood. Here we use
      ancestral protein reconstruction, biochemical experiments, and developmental
      assays of transgenic animals carrying reconstructed ancestral genes to
      investigate how the transcription factor Bicoid (Bcd) evolved its central role in
      anterior-posterior patterning in flies. We show that most of Bcd's derived
      functions are attributable to evolutionary changes within its homeodomain (HD)
      during a phylogenetic interval >140 million years ago. A single substitution from
      this period (Q50K) accounts almost entirely for the evolution of Bcd's derived
      DNA specificity in vitro. In transgenic embryos expressing the reconstructed
      ancestral HD, however, Q50K confers activation of only a few of Bcd's
      transcriptional targets and yields a very partial rescue of anterior development.
      Adding a second historical substitution (M54R) confers regulation of additional
      Bcd targets and further rescues anterior development. These results indicate that
      two epistatically interacting mutations played a major role in the evolution of
      Bcd's controlling regulatory role in early development. They also show how
      ancestral sequence reconstruction can be combined with in vivo characterization
      of transgenic animals to illuminate the historical mechanisms of developmental
      evolution.

PMID- 30298820
TI  - Sensitive and Selective Detection of Mercury Ions in Aqueous Media Using
      Oligonucleotide-Functionalized Nanosensor and SERS Chip.

PMID- 30298821
TI  - A Novel Proof-of-Concept Sandwich Immunoassay for Screening Microcystin in
      Cyanobacteria based on Michael Addition Reaction.

PMID- 30298822
TI  - [The 133th Regional Meeting (Kinki Area)].

PMID- 30298823
TI  - Repeatability of antral follicle count according parity in dairy cows.
AB  - Ovarian reserve in cattle can be predicted by an indicator, the antral follicle
      count (AFC), which is easily determined via ovarian ultrasonography. However, the
      repeatability of AFC measurements in the same individual taken approximately 1
      year apart after first parity remains unclear. This study, thus, aimed to clarify
      the between-lactation repeatability of AFC after first parity in dairy cows. We
      measured the AFC of the same individual cows consecutively across both first and
      second parity, both second and third parity, and both third and fourth parity in
      31, 37, and 26 heads, respectively. The values of the intraclass correlation
      coefficients (ICC) for the AFCs in first-second and second-third parity cows were
      more than 0.8, and the value of the ICC for the AFCs in third-fourth parity cows
      was significantly lower than that in first-second parity cows (P = 0.01).
      Subsequently, based on the average number of AFCs measured at some points from
      first to third parity, we classified the cows into three tertiles: < 11 (low), 11
      15 (intermediate), and >= 15 (high). We then compared the reproductive
      performance of the first through third parity cows among the groups. The hazards
      of pregnancy by 200 days postpartum were higher in the high group than in the
      other groups (P < 0.05). Our findings demonstrate that between-lactation
      repeatability of AFC from first through third parity in dairy cows is very high,
      and that cows with an AFC of >= 15 have a better reproductive performance than
      cows with a low AFC.

PMID- 30298824
TI  - Involvement of interferon-tau in the induction of apoptotic, pyroptotic, and
      autophagic cell death-related signaling pathways in the bovine uterine
      endometrium during early pregnancy.
AB  - Interferon-tau (IFNT), a type I interferon (IFN), is known as pregnancy
      recognition signaling molecule secreted from the ruminant conceptus during the
      preimplantation period. Type I IFNs, such as IFN-alpha and IFN-beta, are known to
      activate cell-death pathways as well as induce apoptosis. In cows, induction of
      apoptosis with DNA fragmentation is induced by IFNT in cultured bovine
      endometrial epithelial cells. However, the status of cell-death pathways in the
      bovine endometrium during the preimplantation period still remains unclear. In
      the present study, we investigated the different cell-death pathways, including
      apoptosis, pyroptosis, and autophagy, in uterine tissue obtained from pregnant
      cows and in vitro cultured endometrial epithelial cells with IFNT stimulation.
      The expression of CASP7, 8, and FADD (apoptosis-related genes) was significantly
      higher in pregnant day 18 uterine tissue in comparison to non-pregnant day 18
      tissue. The expression of CASP4, 11, and NLRP3 (pyroptosis-related genes) was
      significantly higher in the pregnant uterus in comparison to non-pregnant uterus.
      In contrast, autophagy-related genes were not affected by pregnancy. We also
      investigated the effect of IFNT on the expression of cell-death pathway-related
      genes, as well as DNA fragmentation in cultured endometrial epithelial cells.
      Similar to its effects in pregnant uterine tissue, IFNT affected the increase of
      apoptosis-related (CASP8) and pyroptosis-related genes (CASP11), but did not
      affect autophagy-related gene expression. IFNT also increased gammaH2AX-positive
      cells, which is a marker of DNA fragmentation. These results suggest that
      apoptosis- and pyroptosis-related genes are induced by IFNT in the pregnant
      bovine endometrial epithelial cells.

PMID- 30298825
TI  - The roles of kisspeptin in the mechanism underlying reproductive functions in
      mammals.
AB  - Kisspeptin, identified as a natural ligand of GPR54 in 2001, is now considered as
      a master regulator of puberty and subsequent reproductive functions in mammals.
      Our previous studies using Kiss1 knockout (KO) rats clearly demonstrated the
      indispensable role of kisspeptin in gonadotropin-releasing hormone
      (GnRH)/gonadotropin secretion. In addition, behavioral analyses of Kiss1 KO rats
      revealed an organizational effect of kisspeptin on neural circuits controlling
      sexual behaviors. Our studies using transgenic mice carrying a region-specific
      Kiss1 enhancer-driven reporter gene provided a clue as to the mechanism by which
      estrogen regulates Kiss1 expression in hypothalamic kisspeptin neurons. Analyses
      of Kiss1 expression and gonadotropin secretion during the pubertal transition
      shed light on the mechanism triggering GnRH/gonadotropin secretion at the onset
      of puberty in rats. Here, we summarize data obtained from the aforementioned
      studies and revisit the physiological roles of kisspeptin in the mechanism
      underlying reproductive functions in mammals.

PMID- 30298826
TI  - The Effect of Improving Oral Hygiene through Professional Oral Care to Reduce the
      Incidence of Pneumonia Post-esophagectomy in Esophageal Cancer.
AB  - Radical esophagectomy for thoracic esophageal cancer is invasive and frequently
      results in postoperative pulmonary complications. Postoperative pneumonia is the
      most common such complication and affects hospital mortality and survival rates.
      Oral care has been very effective in reducing pneumonia. In Japan, preoperative
      professional oral care is highly recommended. However, there are few studies on
      the effect of preoperative improvements in oral hygiene as a result of
      intervention on the incidence of postoperative pneumonia. The primary end-point
      of this retrospective study was the incidence of postoperative pneumonia after
      radical esophagectomy. The oral health levels of 46 patients were individually
      categorized, and then patients were grouped according to whether they maintained
      or improved their oral hygiene. At the first dental examination, oral health
      levels were classified as good in 22 patients and bad in 24. Of the 46 patients
      studied, 39 patients maintained or improved their oral hygiene (good control
      group), whereas 7 showed no improvement (bad control group). Postoperative
      pneumonia occurred in eight patients: four in the good control group and four in
      the bad control group. Statistical analysis with postoperative pneumonia as a
      dependent variable showed a significant effect of oral hygiene improvement on the
      incidence of pneumonia. Logistic regression analysis with this factor as an
      independent variable demonstrated that the risk of postoperative pneumonia was
      reduced in the good control group (OR 0.086, 95% CI 0.014-0.529). Therefore,
      preoperative professional oral care may improve oral hygiene and oral health,
      which may in turn reduce the incidence of postoperative pneumonia.

PMID- 30298827
TI  - Design, Synthesis, and Screening of 5-Aryl-3-(2-(pyrrolyl)thiophenyl)-1,2,4
      oxadiazoles as Potential Antitumor Molecules on Breast Cancer MCF-7 Cell Line.
AB  - The work reported the design and cytotoxic screening of synthetic small
      molecules: carbonitriles 3a-c, carboximidamides 4a-c, and oxadiazoles 5-19 as
      antitumor molecules. Molecules 4c, 9, 12, and 14 show promising cytotoxicity
      profiles against two cell lines higher than prodigiosin (PG). The results of
      topoisomerase enzyme inhibition assay show that carboximidamide 4c and oxadiazole
      14 display potent inhibitory activity in nano-molar concentration higher than PG.
      In addition, carboximidamide 4c and oxadiazoles 9, 12, and 14 exhibit
      antiproliferative activities over MCF-7 cells by cell cycle arrest at G1 phase
      and apoptosis inducing activity by increasing cell population percentages at pre
      G1 and G2/M phases as shown by DNA-flow cytometry assay and annexin V analysis.
      Moreover, measurement of p53 and cell death mediators, show that carboximidamide
      4c and oxadiazoles 9, 12, and 14 significantly up-regulate p53, Puma and Bax/Bcl
      2 ratio levels. Subsequently, pro-apoptotic activities are confirmed by active
      caspase 3/7 percentages green fluorescence assay.

PMID- 30298828
TI  - Advantage of parenteral nutrition for diarrheic calves.
AB  - This study assessed the advantages of dextrose and amino acid mixture solution as
      parenteral nutrition (PN) therapy for diarrheic calves. Thirty diarrheic calves
      were randomly assigned to receive PN (PN group, n=15) or only dextrose solution
      (Dex group, n=15). The treatment period for the PN group (4.0 days; min-max, 2-10
      days) was significantly shorter than that for the Dex group (6.0 days; min-max, 3
      21 days) (P<0.01). The PN therapy tended to improve plasma diamine oxidase
      activity compared with traditional therapy. One potential association between PN
      therapy and shortened treatment period may be the repair of damaged intestinal
      villi. Although our proposal has limitations, PN therapy suggested the potential
      for new treatment of diarrheic calves.

PMID- 30298829
TI  - LH and testosterone secretions in response to GnRH challenge in pubertal Japanese
      Black beef bulls with normal and abnormal semen.
AB  - Plasma luteinizing hormone (LH) and testosterone concentrations were examined in
      Japanese Black beef bulls with normal and abnormal semen in response to
      gonadotropin releasing hormone (GnRH) challenge at the start (10 months) and
      completion (20 months) of puberty. Bulls with normal semen had higher
      testosterone concentrations after GnRH treatment at 20 months than they did at 10
      months, while LH concentrations did not differ between the two age groups. LH and
      testosterone concentrations were not different between bulls with normal and
      abnormal semen at 20 months. Thus, testosterone secretions in response to the
      GnRH challenge were higher for bulls with normal semen at pubertal completion
      compared to bulls at the start of puberty, but responsiveness of LH to GnRH and
      of testosterone to the LH increment was not altered in bulls with abnormal semen.

PMID- 30298830
TI  - Development of a PCR assay for detection and differentiation of Muscovy duck and
      goose parvoviruses based on NS gene characterization.
AB  - Muscovy duck parvovirus (MDPV) and goose parvovirus (GPV) have both been found to
      cause high mortality and morbidity in Muscovy ducklings. Specific detection is
      often rife with false positives due to high identity at the genomic nucleotide
      level and antigenic similarity between MDPVs and GPVs. In this study,
      significantly variable regions were found, via NS comparison, between MDPV and
      GPV NS genes; however, NS genes were conserved within the MDPV and GPV groups. A
      polymerase chain reaction (PCR) assay for detecting and differentiating MDPVs and
      GPVs was developed with more specificity based on the NS gene characterization.
      The assay detected as low as 103 DNA copies of both the MDPV and GPV strains,
      along with 549 separate base pairs (bp). No bands of the same size from other
      duck pathogens, including duck circovirus, duck enteritis virus, egg drop
      syndrome virus, duck-origin goose hemorrhagic polyomavirus, Escherichia coli,
      Salmonella, Riemerella anatipestifer and Pasteurella multocida were amplified.
      This indicates that this method for performing PCR provides a useful and reliable
      alternative tool for more precise differentiation of MDPV and GPV infection in
      clinical samples.

PMID- 30298831
TI  - Microdiscectomy and Foraminotomy in Cervical Spondylotic Myelopathy and
      Radiculopathy.
AB  - This study was to assess the efficacy of microdiscectomy, cage fixation, and
      right tranuncal foramintomy for the patients suffering from right radiulo
      myelopathy. Anterior cervical foraminotomy was reported to be an effective option
      for the treatment of cervical degenerative radiculopathy but with the problem of
      recurrence. Since Hakuba reported the method of trans-unco-discal approach in
      1976, it was designed as keyhole foraminotomy which was called transuncal
      approach, transpedicular approach or transvertebral approach. In the anterior
      approach, we usually use the right-sided approach because most of us are right
      handed surgeons. We retrospectively investigated our patients who had the right
      foraminal stenosis causing radiculopathy and were treated with microdiscectomy,
      cage fixation, and right keyhole transuncal foraminotomy. Since 2011, 23 patients
      were treated with the manner. All of the 23 patients who had central canal
      stenosis and among the 23 patients, 8 patients showed only right radiculopathy
      and 15 patients showed radiculo-myelopathy. In all patients, the radiculopathy
      disappeared or significantly improved without any complications postoperatively.
      The average of VAS scores was 7.6 +/- 2.2 in preoperative state, 2.8 +/- 2.2 at
      discharge, and 1.1 +/- 1.6 in 1 month after surgery. The average of follow-up
      time was 38.3 months and they had no recurrence of radiculopathy. We showed that
      this manner is effective and one option for the combined disease of right
      foraminal and canal stenosis and we believe that this manner is not complex and
      safe if we can understand the anatomy.

PMID- 30298833
TI  - Intramyocardial Hematoma After Radiofrequency Catheter Ablation.

PMID- 30298832
TI  - Flow Diverter Therapy Using a Pipeline Embolization Device for 100 Unruptured
      Large and Giant Internal Carotid Artery Aneurysms in a Single Center in a
      Japanese Population.
AB  - Flow diverters (FDs) have been developed for intracranial aneurysms difficult to
      treat with conventional endovascular therapy and surgical clipping. We reviewed
      94 patients with 100 large or giant unruptured internal carotid artery (ICA)
      aneurysms treated with Pipeline embolization device (PED) embolization from
      December 2012 to June 2017 at Juntendo University Hospital. The patients' mean
      age was 63.4 years (range, 19-88), and there were 90 women 89.4%. Aneurysm
      locations were: C4 (45), C3 (4), and C2 (51) in ICA segments. Mean aneurysm size
      and neck width were 16.9 +/- 6.8 mm and 8.3 +/- 4.4 mm, respectively, in 40
      symptomatic and 60 asymptomatic aneurysms. Follow-up catheter angiographies of 85
      patients with 90 aneurysms showed no filling in 62 aneurysms (68.9%), entry
      remnant in 16 (17.8%), subtotal filling in 11 (12.2), and total filling in 1
      (1.1%) with a mean follow-up of 10.2 +/- 5.6 months. In-stent stenosis occurred
      in 1 patient and parent artery occlusion in 2 during follow-up. Hemorrhagic
      complications occurred in 4 (4.3%): delayed aneurysm rupture (2) and
      intraparenchymal hemorrhage (2). Ischemic complications with neurological
      symptoms occurred in 2 (2.1%): very delayed device occlusion (1) and
      intraprocedural distal embolism (1). Eighteen patients (45%) showed improvement
      in pre-existing cranial nerve dysfunction because of the aneurysm's mass effect,
      3 patients (7.5%) worsened. One patient died of systemic organ failure
      unassociated with the procedure. Morbidity and mortality rates were 4.3% and
      1.1%, respectively. PED embolization for unruptured large and giant ICA aneurysms
      is safe and efficacious. Physicians should be observant of characteristic risks
      associated with FD therapy.

PMID- 30298834
TI  - Use of Pulmonary Inhalants Remains Remarkably High After Atrial Septal Defect
      Closure.
AB  - BACKGROUND: Post-repair atrial septal defects (ASD) patients are frequently
      discharged from follow-up, but the extent of pulmonary symptoms long-term post
      repair is unknown. Methods and Results: The national CONgenital CORvitia registry
      was linked to the national Drug Registry to investigate all ambulatory-dispensed
      pulmonary inhalants for 2006-2014. ASD patients were compared with age- and sex
      matched referents from the general population. A total of 1,959 adult patients
      (age 42+/-17 years; 66% female; 1,223 [62%] repaired) were included. Compared
      with the referents, ASD patients had more inhalant use, even at long-term post
      repair follow-up (OR=1.81 [95% CI 1.62-2.03]; P<0.001). CONCLUSIONS: ASD patients
      had 2-fold higher inhalant use compared with referents even at long-term post
      repair follow-up, suggesting persistent pulmonary functional impairment.

PMID- 30298836
TI  - Alternative Exercise Intervention for Patients With Severe Peripheral Artery
      Disease - Akt1-Induced Blood Flow Recovery.

PMID- 30298835
TI  - Effect of Hypertension on Aortic Artery Disease-Related Mortality - 3.8-Year
      Nationwide Community-Based Prospective Cohort Study.
AB  - BACKGROUND: Aortic artery disease (AAD), such as aortic dissection or aortic
      aneurysm rupture, is fatal, with an extremely high mortality. Because of its low
      incidence, the risk for the development of AAD has not yet been elucidated.
      Hypertension (HT) is an established risk factor for cardiovascular disease, but
      there has been no prospective study on the effect of HT on AAD-related mortality.
      Methods and Results: We used a nationwide database of 276,197 subjects (aged 40
      75 years) who participated in the annual "Specific Health Check and Guidance in
      Japan" from 2008 to 2010. There were 80 AAD-related deaths during the follow-up
      period of 1,049,549 person-years. On multivariate Cox proportional hazard
      regression, HT was an independent risk factor for AAD-related death in apparently
      healthy subjects. On receiver operating characteristics curve analysis for AAD
      related death, abnormal systolic and diastolic blood pressure (SBP and DBP) were
      130 mmHg and 82 mmHg, respectively. The prediction capacity was significantly
      improved by the addition of SBP to confounding risk factors. Notably, further
      improvement of the C index was observed by addition of DBP to the model with SBP.
      CONCLUSIONS: This is the first report to prospectively show that HT is a risk
      factor for AAD-related death. Both SBP and DBP are of critical importance in the
      primary prevention of AAD-related death in apparently healthy subjects.

PMID- 30298837
TI  - [TRPV4 regulates vascular endothelial permeability during colonic inflammation in
      dextran sulphate sodium-induced murine colitis].
AB  - The transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation
      channel involved in physical sensing in various tissue types. The present study
      aimed to elucidate the function and expression of TRPV4 in colonic vascular
      endothelial cells during dextran sulphate sodium (DSS)-induced colitis. The role
      of TRPV4 in the progression of colonic inflammation was examined in the 2% DSS
      induced murine colitis model using immunohistochemical analysis, Western
      blotting, and Evans blue dye extrusion assay. DSS-induced colitis was
      significantly attenuated in TRPV4-deficient (TRPV4 KO) mice when compared to wild
      type mice. Repeated intrarectal administration of GSK1016790A, a TRPV4 agonist,
      exacerbated the severity of DSS-induced colitis. Bone marrow transfer experiments
      demonstrated a dominant role of TRPV4 in non-haematopoietic cells for DSS-induced
      colitis. DSS treatment upregulated TRPV4 expression in the vascular endothelia of
      colonic mucosa and submucosa. DSS treatment increased vascular permeability,
      which was abolished in TRPV4 KO mice. The DSS-induced increase in vascular
      permeability was further enhanced by intravenous administration of GSK1016790A,
      which was abrogated by a TRPV4 antagonist RN1734. TRPV4 was co-localized with
      vascular endothelial (VE)-cadherin, and VE-cadherin expression was decreased by
      repeated intravenous administration of GSK1016790A during colitis. Furthermore,
      TRPV4 activation by GSK106790A decreased VE-cadherin expression in mouse aortic
      endothelial cells exposed to TNF-alpha. These findings indicate that TRPV4
      upregulation in vascular endothelial cells contributes to the progression of
      colonic inflammation via the activation of vascular permeability. Thus, TRPV4 is
      an attractive target for the treatment of inflammatory bowel diseases.

PMID- 30298838
TI  - [Recent progress in the research of Eosinophilic GastroIntestinal Diseases
      (EGIDs)].
AB  - Eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), which are
      included in eosinophilic gastrointestinal disorders (EGIDs), are allergic
      gastrointestinal diseases mainly caused by food allergens, which features dense
      infiltration of eosinophiles in the gastrointestinal mucosa. A possible mechanism
      of these diseases are Th2 type allergic reactions, including IL-5, IL-13, and IL
      15, thymic stromal protein (TSLP), and eotaxin 3, which are considered to have
      important roles. The number of patients with EoE is rapidly increasing in both
      Western and Asian countries. In Japan, a research group of the Ministry of
      Health, Labor and Welfare has announced recommendations for the diagnosis and
      management of EoE and EGE in 2015. For a diagnosis of EoE, endoscopic
      abnormalities and histological confirmation of dense eosinophile infiltration in
      the esophageal epithelial layer are important, in addition to identifying
      dysphagia symptoms. As for eosinophilic gastroenteritis, blood test findings are
      more useful and the role of an endoscopic examination is reduced. Glucocorticoid
      administration is standard treatment for these diseases, while proton pump
      inhibitors are frequently effective for EoE. As for EoE, on the one hand, a
      variety of studies have been performed and new findings collected. On the other
      hand, information concerning EGE is limited and additional evidence is needed to
      establish effective treatment options.

PMID- 30298839
TI  - [The involvement of NOX1/NADPH oxidase in the development of non-alcoholic
      steatohepatitis].
AB  - Reactive oxygen species (ROS) are known to play a critical role in the
      development of non-alcoholic steatohepatitis (NASH). To clarify the source of
      ROS, we examined the expression of superoxide-generating NADPH oxidase isoforms
      in the liver of high-fat and high-cholesterol (HFC) diet-fed mice. The mRNA
      expression of NOX1 was significantly elevated in mice on HFC diet for 8 weeks.
      Increased levels of serum alanine aminotransferase and hepatic cleaved caspase-3
      in HFC diet-fed wild-type mice (WT) were significantly ameliorated in mice
      deficient in Nox1 (Nox1-KO). Increased nitrotyrosine adduct formation, a marker
      of peroxynitrite-induced injury, was observed in hepatic sinusoids of WT, which
      was significantly suppressed in NOX1-KO. NOX1 mRNA was mainly expressed in liver
      sinusoidal endothelial cells (LSECs), and it was significantly up-regulated in
      primary cultured LSECs treated with palmitic acid (PA). The production of nitric
      oxide by LSECs and LSECs-dependent relaxation of hepatic stellate cells were
      significantly attenuated by PA treatment. In contrast, these effects of PA were
      not observed in cells isolated from Nox1-KO. Taken together, the up-regulation of
      NOX1 in LSECs may elicit peroxynitrite-mediated cellular injury and impair
      hepatic microcirculation through reduced bioavailability of nitric oxide. ROS
      derived from NOX1 may therefore constitute a critical component in the
      development of NASH.

PMID- 30298840
TI  - [Gut microbiota and nonalcoholic steatohepatitis].
AB  - Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis
      (NASH), is a disease that may lead to liver cirrhosis or hepatocellular
      carcinoma. The number of patients is increasing steadily and the pathology is
      diverse. Effective treatment is still mainly focused on diet and exercise
      therapy. With the advent of the next-generation sequencer, the intestinal flora
      in NAFLD/NASH is being elucidated. We believe that elevation of endotoxin in the
      blood caused by intestinal bacterial dysbiosis caused by intestinal permeability
      enhancement is important for NASH pathology and control of intestinal
      permeability enhancement has a new possibility for treatment of NAFLD/NASH.

PMID- 30298841
TI  - [Neurological mechanism and therapeutic strategy for posttraumatic stress
      disorders].
AB  - Posttraumatic stress disorder (PTSD) is most often induced by traumatic events
      and serious public health problems. PTSD is characterized by excessive response
      to contextual memory and impaired fear extinction and also associated with mild
      cognitive impairment, attention and learning deficits. Clinical and animal
      studies suggest that increased susceptibility of emotion- and fear-related
      neuronal circuits, including those in the amygdala, prefrontal cortex and
      hippocampus, contributes to development and retention of PTSD symptoms. However,
      mechanisms underlying this susceptibility to fear are not known and the useful
      therapeutic approaches are limited. Recently, there have been reports that omega3
      LCPUFA supplementation can prevent development of PTSD and significantly
      ameliorate symptoms in patients with PTSD after accidental injury such as motor
      vehicle accidents and natural calamities. Importantly, Fabp7 null mice exhibit
      enhancement of fear memory consolidation and anxiety-related behaviors that
      resemble PTSD-like behaviors in humans. In this review, we focused behavioral
      phenotype of PTSD in Fabp3 null mice. The Fabp3 null mice exhibit cognitive
      deficits, hyperlocomotion and impaired fear extinction, and thus show PTSD-like
      behaviors. Chronic administration of ramelteon, a melatonin receptor agonist,
      improved all PTSD-like behaviors tested in Fabp3-/- mice. Relevant to mechanisms
      underlying impaired fear extinction, we observed that Ca2+/calmodulin-dependent
      protein kinase II (CaMKII) autophosphorylation increases in the basolateral
      amygdala (BLA) but remained unchanges in the hippocampus of Fabp3-/- mice.
      Likewise, the number of c-Fos positive neurons in BLA significantly increased
      after exposure to contextual fear conditions. Finally, chronic ramelteon
      administration restored abnormal c-Fos expression and CaMKII autophosphorylation
      in the BLA of Fabp3-/- mice. Taken together, Fabp3-/- mice show PTSD-like
      behaviors, and ramelteon is an attractive candidate for PTSD therapeutics in
      human.

PMID- 30298842
TI  - [Current progress of research and use of microminipigs in drug development].
AB  - The use of minipigs has been increasing in the areas of pharmacology researches
      and drug development. The microminipig developed by Fuji Micra Inc. (Shizuoka,
      Japan) inherits characteristics of other pig strains showing several similarities
      to humans in anatomy, physiology, omnivorousness and diurnal, but at the same
      time has several advantages over other pig strains because of its small size
      which allows easy keeping, handling and dosing, and saving of test substances.
      The microminipig weighs about 10 kg at the age of 6 months. Canine cages can be
      used to keep the animal. Swine leukocyte antigens (SLA) are defined in each
      individual animal which is useful for testing immunological reactions. As there
      are many similarities in metabolic enzymes and transporters to those in humans,
      the microminipig is a powerful animal model for toxicokinetic studies.
      Unfortunately as in other minipigs the microminipig is not appropriate for embryo
      fetal development studies of antibody drugs due to its poor placental transfer,
      but can be used for other reproductive and developmental studies. Repeat dose
      toxicity, safety pharmacology, immunotoxicity and local tolerance studies should
      be also other arenas of this animal model.

PMID- 30298844
TI  - [Anti-inflammatory action of the transcription factor Nrf2].

PMID- 30298843
TI  - [Extracellular matrix biomarkers for cardiac diseases].

PMID- 30298845
TI  - Principles of precision medicine and its application in toxicology.
AB  - Precision medicine is an approach to developing drugs that focuses on employing
      biomarkers to stratify patients in clinical trials with the goal of improving
      efficacy and/or safety outcomes, ultimately increasing the odds of clinical
      success and drug approval. Precision medicine is an important tool for
      toxicologists to utilize, because its principles can be used to decide whether to
      pursue a drug target, to understand interindividual differences in response to
      drugs in both nonclinical and clinical settings, to aid in selecting doses that
      optimize efficacy or reduce adverse events, and to facilitate understanding of a
      drug's mode-of-action. Nonclinical models such as the mouse and non-human primate
      can be used to understand genetic variation and its potential translation to
      humans, and are available for toxicologists to employ in advance of drugs moving
      into clinical development. Understanding interindividual differences in response
      to drugs and how these differences can influence the drug's risk-benefit profile
      and lead to the identification of biomarkers that enhance patient efficacy and
      safety is of critical importance for toxicologists today, and in the future, as
      the fields of pharmacogenomics and genetics continue to advance.

PMID- 30298846
TI  - Inhibition of L-type calcium channels by Bisphenol A in rat aorta smooth muscle.
AB  - Bisphenol A (BPA) is an endocrine disrupting chemical used on a wide range in
      industry. This compound has been used in the production of polycarbonate plastics
      and epoxy resins. For this reason and their global use, BPA is one of the most
      common environmental chemicals to which humans are exposed. This exposure can
      cause several adverse health outcomes, including at the cardiovascular level. The
      regulation of ion channels in vascular smooth muscle is pivotal and important for
      vasoreactivity, and changes in their flux can be involved in the pathophysiology
      of some cardiovascular diseases. This study aims to analyse in rat aorta whether
      the vasorelaxant effect of BPA is mediated by L-type Ca2+ channels inhibition.
      Using male Wistar rat aorta artery rings in the organ bath we analysed the
      contractility, and to study the activity of calcium current in A7r5 cells we used
      the whole cell configuration of Patch Clamp technique. Regarding the
      contractility experiences we observed that in both NA and KCl contraction, BPA
      caused a rapid and concentration-dependent relaxation. The electrophysiology
      experiments showed that BPA inhibited the basal and BAY K8644-stimulated whole
      cell L-type Ca2+ channel (W-CLTCC) currents, indicating that this drug blocks the
      L-type Ca2+ channels. Our results suggest that BPA inhibits the W-CLTCC, leading
      to the relaxation of vascular smooth muscle.

PMID- 30298847
TI  - Comparative study for carcinogenicity of 7 different multi-wall carbon nanotubes
      with different physicochemical characteristics by a single intraperitoneal
      injection in male Fischer 344 rats.
AB  - The present study comparatively examined carcinogenicity of 7 different multi
      wall carbon nanotubes (MWCNTs) with different physicochemical characteristics.
      Physicochemical characteristics of MWCNTs (referred to as M-, N-, WL-, SD1-, WS-,
      SD2- and T-CNTs in the present study) were determined using scanning electron and
      light microscopes and a collision type inductively coupled plasma mass
      spectrometer. Male Fischer 344 rats (10 weeks old, 15 animals per group) were
      administered MWCNTs at a single intraperitoneal dose of 1 mg/kg body weight, and
      sacrificed up to 52 weeks after the commencement. Fibers of M-, N-, WL- and SD1
      CNTs were straight and acicular in shape, and contained few agglomerates. They
      were relatively long (38-59% of fibers were longer than 5 MUm) and thick (33% to
      more than 70% of fibers were thicker than 60 nm). All of these 4 MWCNTs induced
      mesotheliomas at absolute incidences of 100%. Fibers of WS-, SD2- and T-CNTs were
      curled and tightly tangled to form frequent agglomerates. They were relatively
      short and thin (more than 90% of measured fibers were thinner than 50 nm). WS-
      CNT did not induce mesothelioma, and only one of 15 rat given SD2- or T-CNT
      developed tumor. Any correlations existed between the metal content and neither
      the size or form of fibers, nor the carcinogenicity. It is thus indicated that
      the physicochemical characteristics of MWCNTs are critical for their
      carcinogenicity. The straight and acicular shape without frequent agglomerates,
      and the relatively long and thick size, but not the iron content, may be critical
      factors. The present data can contribute to the risk management, practical use
      and social acceptance of MWCNTs.

PMID- 30298848
TI  - Plasma 2-hydroxyglutarate, a promising prognostic biomarker candidate for
      skeletal muscle injury in Fischer 344 rats.
AB  - Previously, we have demonstrated the potential of plasma 2-hydroxyglutarate (2HG)
      as an easily detectable biomarker for skeletal muscle injury in rats. Here, we
      examined whether plasma 2HG was superior to conventional skeletal muscle damage
      biomarkers, including aspartate aminotransferase (AST), creatine kinase (CK), and
      skeletal muscle-type CK isoenzyme (CK-MM) levels, in rats. Skeletal muscle injury
      was induced in 4- or 9-week-old male Fischer 344 rats by cerivastatin (CER) or
      tetramethyl-p-phenylenediamine (TMPD) administration. Plasma 2HG levels were
      measured on days 4, 8, and 11 (CER group) and at 6 and 24 hr post-administration
      (TMPD group). Plasma AST, CK, and CK-MM activities and histopathological changes
      in the rectus femoris muscle were evaluated at the study endpoints. In the CER
      group, AST, CK, and CK-MM increased in 4- and 9-week-old rats, whereas increases
      in CK (4- and 9-week-old rats) and CK-MM (4-week-old rats) were not obvious in
      the TMPD group. In both 4- and 9-week-old rats, plasma 2HG increased on day 8 and
      at 24 hr post-administration in the CER and TMPD groups, respectively.
      Histopathological analysis revealed myofiber vacuolation and necrosis in both
      groups. The histopathological damage to the rectus femoris muscle was more severe
      in the CER than in the TMPD group. Increased plasma 2HG was associated with CER-
      and TMPD-induced skeletal muscle injuries in rats and was not affected by age
      differences or repeated blood collection. The results suggest that plasma 2HG is
      superior to CK and CK-MM as a biomarker for mild skeletal muscle injury.

PMID- 30298850
TI  - One-Year Follow-up After Tetralogy of Fallot Total Repair Preserving Pulmonary
      Valve and Avoiding Right Ventriculotomy.
AB  - BACKGROUND: We reviewed our revised surgical strategy for tetralogy of Fallot
      (TOF) total correction to minimize early exposure to significant pulmonary
      regurgitation (PR) and to avoid right ventriculotomy (RV-tomy). Methods and
      Results: Since February 2016, we have tried to preserve, first, pulmonary valve
      (PV) function to minimize PR by extensive commissurotomy with annulus saving; and
      second, RV infundibular function by avoiding RV-tomy. With this strategy, we
      performed total correction for 50 consecutive patients with TOF until May 2018.
      We reviewed the early outcomes of 27 of 50 patients who received follow-up for
      >=3 months. Mean patient age at operation was 10.2+/-5.0 months, and mean body
      weight was 8.8+/-1.2 kg. The preoperative pressure gradient at the RV outflow
      tract and the PV z-score were improved at most recent echocardiography from
      82.0+/-7.1 to 26.8+/-6.4 mmHg, and from -2.35+/-0.49 to -0.55+/-0.54,
      respectively, during 11.1+/-1.6 months of follow-up after operation. One patient
      required re-intervention for residual pulmonary stenosis. Twenty-two patients had
      less than moderate PR (none, 1; trivial, 8; mild, 13), and 5 patients had
      moderate PR. There was no free or severe PR. CONCLUSIONS: At 1-year follow-up,
      the patients who underwent total TOF correction with our revised surgical
      strategy had acceptable results in terms of PV function. The preserved PV had a
      tendency to grow on short-term follow-up.

PMID- 30298849
TI  - Differential impacts of mineralocorticoid receptor antagonist potassium
      canrenoate on liver and renal changes in high fat diet-mediated early
      hepatocarcinogenesis model rats.
AB  - Mineralocorticoid receptor (MR)/NADPH oxidase (NOX) signaling is involved in the
      development of obesity, insulin resistance, and renal diseases; however, the role
      of this signaling on steatotic preneoplastic liver lesions is not fully
      elucidated. We determined the effects of the MR antagonist potassium canrenoate
      (PC) on MR/NOX signaling in hepatic steatosis and preneoplastic glutathione S
      transferase placental form (GST-P)-positive liver foci. Rats were subjected to a
      two-stage hepatocarcinogenesis model and fed with basal diet or high fat diet
      (HFD) that was co-administered with PC alone or in combination with the
      antioxidant alpha-glycosyl isoquercitrin (AGIQ). PC reduced obesity and renal
      changes (basophilic tubules that expressed MR and p22phox) but did not affect
      blood glucose tolerance and non-alcoholic fatty liver disease activity score
      (NAS) in HFD-fed rats. However, the drug increased the area of GST-P-positive
      liver foci that expressed MR and p22phox as well as increased expression of NOX
      genes (p22phox, Poldip2, and NOX4). PC in combination with AGIQ had the potential
      of inhibiting the effects of PC on the area of GST-P-positive liver foci and the
      effects were associated with increasing expression of an anti-oxidative enzyme
      (Catalase). The results suggested that MR/NOX signaling might be involved in
      development of preneoplastic liver foci and renal basophilic changes in HFD-fed
      rats; however, the impacts of PC were different in each organ.

PMID- 30298851
TI  - Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis Complicated by
      Sigmoid Septum.
AB  - BACKGROUND: In patients undergoing transcatheter aortic valve replacement (TAVR)
      for severe aortic stenosis (AS), a sigmoid septum, characterized by subaortic
      interventricular hypertrophy, often results in the need for new pacemaker
      implantation (PMI). In this study, we reviewed the feasibility and treatment
      efficacy of TAVR for AS in patients with a sigmoid septum. Methods and Results:
      Between 2011 and 2016, 48 patients (25.4%; mean age 84.9+/-5.4 years; 9 males)
      with a sigmoid septum and 141 (74.6%; mean age 82.9+/-5.5 years; 61 males)
      without underwent TAVR. Their operative outcomes, echocardiographic and
      electrocardiographic findings, and long-term outcomes were retrospectively
      compared. Second TAVR because of valve malposition was performed in 3 patients
      with a sigmoid septum (6.3%) and in 2 patients without a sigmoid septum (1.4%),
      with no significant difference between the 2 groups. Although there was no
      significant difference in valve hemodynamics between the 2 groups, sigmoid septum
      and deep implantation (implantation depth >=10 mm) were independent predictors of
      new PMI following TAVR. CONCLUSIONS: Although a sigmoid septum did not preclude
      the feasibility, safety, or efficacy of TAVR for severe AS, its presence was
      associated with new PMI. Our approach to TAVR in patients with a sigmoid septum
      may contribute to clinical outcomes comparable to those of patients without this
      pathology.

PMID- 30298853
TI  - Is Transesophageal Echocardiography Necessary in Every Case of Atrial
      Fibrillation Ablation?

PMID- 30298852
TI  - Prognostic Impact of Computed Tomography-Derived Abdominal Fat Area on
      Transcatheter Aortic Valve Implantation.
AB  - BACKGROUND: Obesity has previously been identified as an indicator of good
      prognosis in patients undergoing transcatheter aortic valve implantation (TAVI),
      an association known as the "obesity paradox". We investigated whether abdominal
      total fat area (TFA), visceral fat area (VFA), or subcutaneous fat area (SFA) are
      prognostic indicators of long-term clinical outcome in patients undergoing TAVI.
      Methods and Results: We retrospectively analyzed 100 consecutive patients who
      underwent TAVI between December 2013 and April 2017. TFA, VFA, and SFA were
      measured from routine pre-procedural computed tomography (CT). Patients were
      divided into 2 groups according to median TFA, VFA, or SFA, and we investigated
      the association of abdominal fat area with adverse clinical events, including all
      cause death and re-hospitalization due to worsening heart failure. At a median
      follow-up of 665 days, patients with higher SFA had significantly lower incidence
      of the composite outcome and all-cause death compared with patients with lower
      SFA (15.0% vs. 37.7%, P=0.025; and 8.9% vs. 23.7%, P=0.047, respectively). In
      contrast, patients with higher TFA or VFA did not show significant reduction in
      the incidences of the composite outcome or all-cause mortality. CONCLUSIONS: CT
      derived SFA had prognostic value in patients undergoing TAVI.

PMID- 30298854
TI  - Effects of different resin sealing therapies on nanoleakage within artificial non
      cavitated enamel lesions.
AB  - The aim of this study was to evaluate nanoleakage within the different lesion
      sealing therapies applied to artificial non-cavitated enamel lesions. Thirty-two
      human anterior teeth were used. Artificial subsurface enamel lesions were
      produced on the labial surfaces of teeth. The specimens were then randomly
      divided into three groups (n=10): Group I- Clinpro Sealant application; Group II-
      ExciTE F adhesive resin application; and Group III- ICON resin infiltrant
      application. Each group was further divided into two subgroups: control and
      thermocycler. Nanoleakage was calculated by the digital image analysis software.
      In the control and thermocycled groups, there was no statistically significant
      difference between the Groups I, II, and III (p>0.05). The only significant
      leakage scores were obtained between the Group III control and thermocycler
      groups (p=0.027). ICON infiltrant can be used as an alternative to dental
      adhesives and fissure sealants in the sealing of initial non-cavitated enamel
      lesions. But the resin may become more affected by the water sorption than other
      resin materials over time. More studies are needed to evaluate long-term
      durability of resin infiltrants.

PMID- 30298855
TI  - Effect of kinematic viscosity on the staining performance of caries detector
      dyes.
AB  - The relationship between performance of caries detector dyes and solvent
      molecular weight has been reported, but viscosity has not yet been investigated.
      Therefore, using extracted human teeth, we compared 6 experimental caries
      detector dyes with different viscosities to clarify the relationship between dye
      viscosity and staining performance in sclerotic dentin. Carious dentin started
      showing dentin staining when stained with caries detector dyes with kinematic
      viscosity>=263 mm2/s, showed no immunoreactivity for Streptococcus mutans on
      immunohistochemistry, and contained dentinal tubules free of debris on scanning
      electron microscopy. Samples stained using a caries detector dye with kinematic
      viscosity of 332 mm2/s contained calcification product-like debris in the
      dentinal tubules. These findings suggest that the caries detector dye has a
      threshold kinematic viscosity between 263 and 332 mm2/s at which sclerotic dentin
      and tissues beyond are not stained. The caries detector dye appears to control
      tooth dyeability based on solvent viscosity.

PMID- 30298856
TI  - Changes in the physical properties and color stability of aesthetic restorative
      materials caused by various beverages.
AB  - This study investigates the effects of various beverages on the wettability,
      microhardness, and color stability of aesthetic dental restorative materials. A
      contact angle analyzer, Vickers hardness tester, and spectrophotometer were used
      to characterize the properties of the materials and a total of 225 specimens were
      prepared: 75 each for a resin composite, compomer, and giomer. Ingestion of
      energy drinks and cola caused the greatest deterioration in wettability and
      microhardness, and coffee caused the most significant color change. In addition,
      the change in the resin composite was lower than that of the other restorative
      materials. The extent of change in the restorative materials increased with
      duration and frequency of contact with the beverages, so a reduction in the
      frequency of ingestion of these beverages is recommended.

PMID- 30298857
TI  - Structural and long-term mechanical properties from a resin-modified glass
      ionomer cement after various delays of light-activation.
AB  - This study aimed, after various delays of light-activation, to examine the
      microstructure of a resin-modified glass ionomer cement (RMGIC) by scanning
      electron microscopy (SEM) and to test its mechanical properties in short and long
      term. Five groups of Fuji II LC were investigated with different light-curing
      protocols. For each, SEM observations were undertaken with etched samples to
      selectively observe the organic polymer phase. Flexural strength and
      microhardness were also tested after 24 h and 12 months storage. SEM examination
      showed different images of the material according to the delay of light
      activation. At 24 h, there was a delay with maximal mechanical properties: 5 min
      for flexural strength, 10 min for microhardness. However, at 12 months, maximal
      mechanical properties were reached for the shortest delay. The competition
      between the acid-base and polymerization reactions results in the formation of a
      structurally and mechanically different material according to the delay of light
      activation. This delay should be adapted to the clinical situation.

PMID- 30298858
TI  - Ultrastructure and bonding properties of tribochemical silica-coated zirconia.
AB  - Tribochemical silica coating (TSC) is commonly used to pretreat zirconia surfaces
      prior to luting. Although many studies demonstrate an adhesion-promoting effect
      of TSC on zirconia, its actual interaction mechanism has not been fully
      elucidated. We therefore characterized the ultrastructure of TSC-treated zirconia
      and tested shear-bond strength. STEM/EDS disclosed a micro-roughened zirconia
      surface partially covered with fused Al and Si, while residual unfused silica
      particles could also still be detected. TSCtreated zirconia having received the
      solely silane primer exhibited a significantly lower shear-bond strength than
      zirconia on which the combined 10-MDP/silane primer was applied. SEM fracture
      analysis revealed residual silica particles on both the zirconia and cement
      sides. Correlative ultrastructural and chemical surface characterization revealed
      that TSC deposited an inhomogeneous silica layer on the zirconia surface, which
      explains why the solely silane coupling agent was less effective than the
      combined 10-MDP/silane ceramic primer for bonding to zirconia pretreated by TSC.

PMID- 30298859
TI  - Microhardness of bovine enamel after different fluoride application protocols.
AB  - The aim of the present study was to evaluate microhardness, mineral recovery and
      the enamel surface after the application of topical fluoride to artificial dental
      caries. Twenty-five bovine enamel blocks were prepared for artificial caries-like
      lesions and randomly divided into five groups (n=5): untreated (C control), 1.23%
      acidulated phosphate fluoride gel (APG), 2% neutral fluoride gel (NFG), 1.23%
      acidulated fluoride mousse (AFM) and fluoride varnish (5% Duraphat, DFV). Knoop
      microhardness (KHN) was evaluated after 7 and 14 days of treatment as well as 1
      week after 28 days of treatment. Electron and confocal microscopy and energy
      dispersive spectroscopy were performed. KHN data were treated with two-way ANOVA
      (material*time) and Tukey's test at a 5% significance level. Differences were
      found among groups over time (p<0.001). Microhardness varied after 7 and 14 days
      of treatment and remained stable 1 week after 28 days of treatment. Mineral
      recovery and enamel topography varied among groups, with the fluoride varnish
      achieving the most uniform topography.

PMID- 30298860
TI  - Microtensile bond strengths of adhesively bonded polymer-based CAD/CAM materials
      to dentin.
AB  - This in vitro study aimed to evaluate the effect of two different polymer-based
      CAD/CAM materials; resin-nano ceramic (Lava Ultimate [LVU]) and composite
      (CERASMART [CS]), their different surface pre-treatments, and use of different
      resin cements on the uTBS of adhesively bonded CAD/CAM onlays to dentin. CAD/CAM
      materials were cut into slabs and divided into five groups according to the
      surface pre-treatments applied: Silane Primer, OptiBond XTR adhesive, Silane
      Primer+OptiBond XTR adhesive, Single Bond Universal (SBU), and RelyX Ceramic
      Primer+SBU. The LVU and CS specimens were bonded to the mid-coronal dentin of 50
      noncarious human molars using NX3 resin cement with OptiBond XTR or RelyX
      Ultimate with SBU. uTBS was evaluated after 5,000 thermocycling and analysed with
      three-way-ANOVA and post-hoc Tukey's tests (p<0.05). The uTBS was significantly
      influenced by the type of CAD/CAM material (p<0.0001) surface pre-treatments
      (p<0.05) and resin cements (p<0.05). Regardless of the pre-treatments and resin
      cements, bonding of the composite CAD/CAM material to dentin was higher than the
      resin nano-ceramic material.

PMID- 30298861
TI  - Regional differences in colorectal cancer mortality between 2000 and 2013 in
      Republic of Korea.
AB  - OBJECTIVE: Colorectal cancer (CRC) is the 4th common site for cancer death in
      Republic of Korea. The aim of this study was to describe the trends of colorectal
      cancer mortality by regions. METHODS: CRC mortality trends in Republic of Korea
      by region were described using a Joinpoint regression model in both sexes. The
      annual percent changes (APC) were calculated for each segment. Visualization of
      the changes in mortality rate of colorectal cancer death rates by 16 geographic
      areas in both sexes between 2000-2004 and 2009-2013 were also conducted. RESULTS:
      CRC mortality rates of men showed decreasing trend after increase in Daegu,
      Gyeongsangnam-do and Chungcheongbuk-do between 2000 and 2013 based on the
      joinpoint model. While, Gwangju, Jeollabuk-do, Jeollanam-do, Gyeongsangbuk-do
      showed increase in CRC mortality during the same period. For women, CRC mortality
      of Seoul, Incheon, Daejeon and Gyeongsangnam-do started to decrease in 2005,
      2003, 2007 and 2006 respectively. The mortality rate for CRC in the eastern
      regions, which had relatively low rates of CRC among men in 2000 to 2004, reached
      a level similar to that in the northwestern regions of 2009 to 2013, while the
      highest CRC mortality rates in women was observed in Chungcheongbuk-do.
      CONCLUSIONS: Reduction in CRC mortality varied across 16 metropolitan cities and
      provinces in men, and the visualization pattern showed that the east side of
      South Korea had the least progress in mortality reduction.

PMID- 30298862
TI  - Older Adult Males Who Worked at Small-sized Workplaces Have an Increased Risk of
      Decline in Instrumental Activities of Daily Living: A Community-based Prospective
      Study.
AB  - BACKGROUND: To examine the relationship of working history from early adulthood
      through old age with instrumental activities of daily living (IADL). METHODS:
      Analyzed participants were 5,857 community-dwelling older Japanese people aged
      >=65. Using the Tokyo Metropolitan Institute of Gerontology Index of Competence,
      IADL decline was defined as individuals who had no IADL dependence at baseline,
      but were deemed as dependent in IADL at follow-up. Work history was based on
      working status at baseline, total working years, and information concerning the
      longest held job, including occupation, employment pattern, and workplace size
      (number of employees). We conducted multiple logistic regression analyses and
      estimated the odds ratio (OR) for IADL decline with 95% confidence interval (CI)
      by gender. RESULTS: At the 33-month follow-up, 428 men (16.6%) and 275 women
      (8.4%) developed IADL decline. After covariate adjustments, men with unstable
      employment reported significantly increased IADL decline (OR=1.52, 95% CI=1.19
      1.95) compared to men with stable employment, and men who worked in small
      workplaces with 1-49 employees had an increased risk for IADL decline (1.53, 1.21
      1.93) compared to men in large-sized workplaces with >=50 employees. After mutual
      adjustment for all working history items, only the association between small
      workplaces and IADL decline remained significant in men (1.37, 1.03-1.84). Among
      women, none of working history items was associated with IADL decline.
      CONCLUSION: Our results suggest that not only promoting older people's workforce
      participation, but also providing workers employed at small workplaces with
      sufficient occupational health services, may be effective in helping retain male
      IADL in later life.

PMID- 30298863
TI  - Japanese Legacy Cohort Studies: The Hisayama Study.
AB  - The Hisayama Study is a population-based prospective cohort study designed to
      evaluate the risk factors for lifestyle-related diseases, such as stroke,
      coronary heart disease, hypertension, diabetes, and dementia, in a general
      Japanese population. The prospective follow-up surveys have been conducted in
      subjects aged 40 or older since 1961. Notable characteristics of this study
      include its high participation rate (70-80% of all residents aged 40 or older),
      high follow-up rate (99% or over), and high autopsy rate (approximately 75% of
      deceased cases). The Hisayama Study has provided valuable evidence of secular
      change in the prevalence and incidence of several lifestyle-related disease and
      their risk factors. The study has thereby contributed to elucidation of the
      preventive strategies for lifestyle-related disease. Research efforts in this
      cohort are ongoing and will provide additional data for the improvement of human
      health and longevity.

PMID- 30298864
TI  - Perceived barriers to career progression among early-career epidemiologists 
      report of a workshop at the 22nd World Congress of Epidemiology.

PMID- 30298865
TI  - Improvement of Glucose Metabolism Following Long-Term Taurocholic Acid Gavage in
      a Diabetic Rat Model.
AB  - BACKGROUND Bile acids (BAs) are signaling molecules that participate in
      maintaining glucose homeostasis. Acute enteral infusion of BAs potently reduces
      the glycemic response to glucose, associated with an increase of incretin
      hormones. However, the effect of long-term supplementation of BAs on glucose
      metabolism has not been fully investigated. MATERIAL AND METHODS Thirty diabetic
      rats were assigned to a control group (n=10), a low TCA group (L-TCA group,
      n=10), and a high TCA group (H-TCA group, n=10). Rats in the control group were
      fed a regular high-fat diet (HFD), while rats in the L-TCA group and H-TCA group
      were fed a TCA (taurocholic acid)-mixed HFD with the concentrations of 0.05% and
      0.3%, respectively, to control the intake of HFD and TCA. Energy intake, body
      weight, serum insulin, glucose tolerance, insulin sensitivity, GLP-1, and total
      serum BAs were measured at week 2 and week 12. RESULTS At week 2 there were no
      significant differences in body weight, daily energy intake, glucose tolerance,
      serum insulin, insulin sensitivity, GLP-1, or fasting total serum BAs between the
      3 groups. At week 12, fasting blood glucose and intragastric glucose tolerance
      were better in the H-TCA group, with significantly greater insulin and GLP-1
      secretion and better insulin sensitivity; no significant differences in body
      weight, energy intake, or total fasting serum BAs were observed. CONCLUSIONS Long
      term supplementation with small doses of TCA was demonstrated to improve glucose
      metabolism in a diabetic rat model and may be a potential target for diabetes
      control.

PMID- 30298867
TI  - Recent advances in single cell manipulation and biochemical analysis on
      microfluidics.
AB  - Single cell analysis has become of great interest with unprecedented capabilities
      for the systematic investigation of cell-to-cell variation in large populations.
      Rapid and multi-parametric analysis of intercellular biomolecules at the single
      cell level is imperative for the improvement of early disease diagnosis and
      personalized medicine. However, the small size of cells and the low concentration
      levels of target biomolecules are critical challenges for single cell analysis.
      In recent years, microfluidic platforms capable of handling small-volume fluid
      have been demonstrated to be powerful tools for single cell analysis. In
      addition, microfluidic techniques allow for precise control of the localized
      microenvironment, which yield more accurate outcomes. Many different microfluidic
      techniques have been greatly improved for highly efficient single-cell
      manipulation and highly sensitive detection over the past few decades. To date,
      microfluidics-based single cell analysis has become the hot research topic in
      this field. In this review, we particularly highlight the advances in this field
      during the past three years in the following three aspects: (1) microfluidic
      single cell manipulation based on microwells, micropatterns, droplets, traps and
      flow cytometric methods; (2) detection methods based on fluorescence, mass
      spectrometry, electrochemical, and polymerase chain reaction-based analysis; (3)
      applications in the fields of small molecule detection, protein analysis,
      multidrug resistance analysis, and single cell sequencing with droplet
      microfluidics. We also discuss future research opportunities by focusing on key
      performances of throughput, multiparametric target detection and data processing.

PMID- 30298866
TI  - P-glycoprotein targeted photodynamic therapy of chemoresistant tumors using
      recombinant Fab fragment conjugates.
AB  - P-glycoprotein (Pgp) has been considered as a major cause of cancer multidrug
      resistance; however, clinical solutions to overcome this drug resistance do not
      exist despite the tremendous endeavors. The lack of cancer specificity is a main
      reason for clinical failure of conventional approaches. Targeted photodynamic
      therapy (PDT) is highly cancer specific by combining antibody targeting and
      locoregional light irradiation. We aimed to develop Pgp-targeted PDT using
      antibody-photosensitizer conjugates made of a recombinant Fab fragment. We
      prepared the photosensitizer conjugates by expressing a recombinant Fab fragment
      and specifically linking IR700-maleimide at the C-terminal of the Fab heavy
      chain. In vitro studies showed that the Fab conjugates specifically bind to Pgp.
      Their phototoxicity was comparable to full antibody conjugates when assayed with
      conventional 2-D cell culture, but they outperformed the full antibody conjugates
      in a 3-D tumor spheroid model. In a mouse xenograft model of chemoresistant
      tumors, Fab conjugates showed Pgp specific delivery to chemoresistant tumors.
      Upon irradiation with near-infrared light, they caused rapid tumor shrinkage and
      significantly prolonged the survival of tumor-bearing mice. Compared to the full
      antibody conjugates, Fab conjugates took a shorter time to reach peak tumor
      levels and achieved a more homogeneous tumor distribution. This allows light
      irradiation to be initiated at a shorter time interval after the conjugate
      injection, and thus may facilitate clinical translation. We conclude that our
      targeted PDT approach provides a highly cancer-specific approach to combat
      chemoresistant tumors, and that the conjugates made of recombinant antibody
      fragments are superior to full antibody conjugates for targeted PDT.

PMID- 30298868
TI  - The growth and fluorescence of phthalocyanine monolayers, thin films and
      multilayers on hexagonal boron nitride.
AB  - Free-base phthalocyanine forms distinct interfacial phases and thin films on
      hexagonal boron nitride including a monolayer arrangement as determined using
      high resolution atomic force microscopy. The phases reveal significant
      differences in photoluminescence with an intense peak for monolayer coverages of
      flat-lying molecules which is red-shifted in agreement with theoretical models.

PMID- 30298869
TI  - Intramolecular interaction suggests an autosuppression mechanism for the innate
      immune adaptor protein MyD88.
AB  - MyD88 (myeloid differentiation factor 88) is an important protein in innate
      immunity. Two structural domains of MyD88 have been well characterized
      separately, but the global architecture of full-length MyD88 remained unclear.
      Here, we propose an autosuppressive mechanism of MyD88 regulated by the
      intramolecular interaction between the two domains.

PMID- 30298870
TI  - A lotus-inspired janus hybrid film enabled by interfacial self-assembly and in
      situ asymmetric modification.
AB  - A lotus leaf inspired Janus hybrid film was exquisitely fabricated through a self
      assembly process at the air/water interface with subsequent in situ asymmetric
      modification at the oil/water interface. The interfacial asymmetric decoration
      strategy thus provides a novel pathway for achieving a 2D Janus hybrid film with
      asymmetric wettability and functionality.

PMID- 30298871
TI  - Rational design of a lipid-droplet-polarity based fluorescent probe for potential
      cancer diagnosis.
AB  - A robust fluorescent probe CTPA has been rationally designed for cancer diagnosis
      by monitoring lipid drop (LD) polarity and number variation. With the outstanding
      properties of CTPA, we have shown that the diagnosis of cancer can be achieved
      not only at the cellular levels but also in organs and living mice for the first
      time.

PMID- 30298874
TI  - Re-entrant supramolecular interactions in inverse-melting alpha-cyclodextrin.4
      methylpyridine.water mixtures: an NMR study.
AB  - Inverse melting alpha-cyclodextrin.4-methylpyridine.H2O ternary mixtures were
      studied via solution, high-resolution magic-angle-spinning and 2D-NOESY NMR
      spectroscopy with the aim of unveiling the supramolecular driving force for the
      unusual inverse-melting phase transition. The role of solvent-solvent
      interactions as well as solvent-solute interactions in the emergence of the
      inverse-melting phenomenon is revealed. A surprising re-entrant solvent-solvent
      interaction is found in the system and in the 4-methylpyridine.water solvent
      system, supporting the non-coincidental relationship between inverse melting and
      re-entrant phase transitions, at least in the present system.

PMID- 30298877
TI  - The peculiar effect of water on ionic liquids and deep eutectic solvents.
AB  - Ionic liquids (ILs) and deep eutectic solvents (DESs) have been suggested as eco
      friendly alternatives to organic solvents. A trace amount of water is often
      unavoidable as impurity, and water is also added on purpose to reduce their
      problematically high viscosity and lower their high price. Understanding the
      distinct effects of water on the properties of ILs/DESs is highly important. In
      this review, we collect published experimental and theoretical results for IL/DES
      H2O systems at varied water concentrations and analyze them. Results from
      mechanistic studies, thermodynamic modelling and advanced experiments are
      collected and critically discussed. Six commonly studied IL/DES-H2O systems were
      selected to map experimental observations onto microscopic results obtained in
      mechanistic studies. A great variety of distinct contours of the excess
      properties can be observed over the entire compositional range, indicating that
      the properties of IL/DES-H2O systems are highly unpredictable. Mechanistic
      studies clearly demonstrate that the added H2O rapidly changes the heterogeneous
      3D structures of pure ILs/DESs, leading to very different properties and
      behaviour. There are similarities between aqueous electrolytes and IL/DES
      solutions but the bulky and asymmetric organic cations in ILs/DESs do not conform
      to the standard salt dissolution and hydration concepts. Thermodynamic modelling
      previously assumes ILs/DESs to be either a neutral ion-pair or completely
      dissociated ions, neglecting specific ion hydration effects. A new conceptual
      framework is suggested for thermodynamic modelling of IL/DES-H2O binary systems
      to enable new technologies for their practical applications.

PMID- 30298878
TI  - Exciton localization in excited-state dynamics of a tetracene trimer: a surface
      hopping LC-TDDFTB study.
AB  - Excitons in the molecular aggregates of chromophores are key participants in
      important processes such as photosynthesis or the functioning of organic
      photovoltaic devices. Therefore, the exploration of exciton dynamics is crucial.
      Here we report on exciton localization during excited-state dynamics of the
      recently synthesized tetracene trimer [Liu et al., Org. Lett., 2017, 19, 580]. We
      employ the surface hopping approach to nonadiabatic molecular dynamics in
      conjunction with the long-range corrected time-dependent density functional tight
      binding (LC-TDDFTB) method [Humeniuk and Mitric, Comput. Phys. Commun., 2017,
      221, 174]. Utilizing a set of descriptors based on the transition density matrix,
      we perform comprehensive analysis of exciton dynamics. The obtained results
      reveal an ultrafast exciton localization to a single tetracene unit of the trimer
      during excited-state dynamics, along with exciton transfer between units.

PMID- 30298880
TI  - Rechargeable redox flow batteries: flow fields, stacks and design considerations.
AB  - Rechargeable redox flow batteries are being developed for medium and large-scale
      stationary energy storage applications. Flow batteries could play a significant
      role in maintaining the stability of the electrical grid in conjunction with
      intermittent renewable energy. However, they are significantly different from
      conventional batteries in operating principle. Recent contributions on flow
      batteries have addressed various aspects, including electrolyte, electrode,
      membrane, cell design, etc. In this review, we focus on the less-discussed
      practical aspects of devices, such as flow fields, stack and design
      considerations for developing high performance large-scale flow batteries.
      Finally, we provide suggestions for further studies on developing advanced flow
      batteries and large-scale flow battery stacks.

PMID- 30298881
TI  - Conformationally flexible arylethynyl bis-urea receptors bind disparate oxoanions
      with similar, high affinities.
AB  - Conformationally flexible hosts with relatively small binding pockets are seldom
      shown to bind oxoanions preferentially over other guests. Herein, we disclose the
      binding of diprotic, monoprotic, and aprotic tetrahedral oxoanions with three
      different pyridylethynyl bis-urea scaffolds. In less polar solvent, the trend in
      association constants appears to be heavily influenced by solvation and entropic
      effects. However, in a more polar solvent, the trend in association constants
      matches that of the pKa of the conjugate acid of the anionic guest, as expected
      for H-bond donating hosts.

PMID- 30298882
TI  - Terephthalate-based cobalt hydroxide: a new electrode material for
      supercapacitors with ultrahigh capacitance.
AB  - Searching for new electrode materials is one of the key tasks in developing high
      performance supercapacitors. In this work, as a layered hydroxyl derivative,
      terephthalate-based cobalt hydroxide, Co2(OH)2(C8H4O4), is successfully prepared
      in situ on nickel foam through a simple hydrothermal route. The scanning electron
      microscopy results reveal that the products are composed of massive double-blade
      lath crystals grown along the a-axis. The as-obtained Ni-foam-supported
      Co2(OH)2(C8H4O4) is directly used as the positive electrode of supercapacitors
      without further treatment. The resulting Co2(OH)2(C8H4O4) electrode exhibits
      ultrahigh charge storage capacity with the specific capacity of 9.36 C cm-2 (1261
      C g-1) at a current density of 10 mA cm-2 (0.5 A g-1) and good cycling stability
      with the capacity retention of 82.4% over 5000 cycles at a current density of 50
      mA cm-2. In combination with activated carbon as the negative electrode in 3 M
      KOH aqueous electrolyte, the constructed asymmetric supercapacitor delivers a
      high energy density of 30.62 W h kg-1 at a power density of 221 W kg-1 within a
      voltage window of 1.5 V. These encouraging electrochemical performances enable
      the developed terephthalate-based cobalt hydroxide to be a promising electrode
      material for supercapacitor applications.

PMID- 30298883
TI  - Applying MOF+ technique for in situ preparation of a hybrid material for
      hydrogenation reaction.
AB  - In this study, we present the first case of applying the MOF+ technique for in
      situ preparation of a hybrid material, namely, Zn-MOF-74@ (Pd@Fe2O3). This as
      synthesized material can well maintain both the integrity of the framework and
      porosity. Notably, Zn-MOF-74@(Pd@Fe2O3) exhibits outstanding catalytic
      performance in the hydrogenation reaction of alkene and semihydrogenation
      reaction of phenylacetylene, thus providing a new guideline for the design of MOF
      based hybrid materials for catalytic purpose.

PMID- 30298884
TI  - Facile synthesis and magnetic and electrical properties of layered chalcogenides
      K2CoCu3Q4 (Q for S and Se).
AB  - Layered transition-metal chalcogenides have attracted great interest due to their
      unique electronic and optical properties. Here, we represent two layered
      quaternary chalcogenides K2CoCu3S4 and K2CoCu3Se4 prepared by a convenient
      hydrothermal route. From powder XRD and TEM analyses, K2CoCu3Q4 possesses a
      tetragonal ThCr2Si2-type structure with a random arrangement of Co and Cu atoms.
      The phase purity of the samples was confirmed by ICP, SEM, and EDS analyses, and
      the oxidation states of Co and Cu atoms were determined to be +3 and +1 by XPS
      spectra. Both samples show a weak ferromagnetic behavior at low temperature
      induced by spin-canted antiferromagnetic ordering. The temperature dependent
      resistivity, rho(T), reveals a metallic nature for stoichiometric K2CoCu3S4. The
      semiconducting behavior of K2CoCu3Se4 could be explained better by variable range
      hopping (VRH) rather than adiabatic small polaron hopping (SPH). This new series
      of layered chalcogenides may offer a promising candidate for potential electronic
      applications.

PMID- 30298888
TI  - Synthesis of 2-aminobenzophenones through acylation of anilines with alpha
      oxocarboxylic acids assisted by tert-butyl nitrite.
AB  - In this paper, a regioselective, efficient and convenient synthesis of 2
      aminobenzophenones through acylation of anilines with alpha-oxocarboxylic acids
      assisted by tert-butyl nitrite is presented. Interestingly, tert-butyl nitrite
      acts as not only an efficient and mild nitrosation reagent, but also a
      sustainable oxidant required in the Pd(ii)-catalyzed decarboxylative acylation.
      Meanwhile, the NO unit turned out to be an easily introduced and readily
      removable directing group for the regioselective acylation.

PMID- 30298891
TI  - Sub-kT/q switching in In2O3 nanowire negative capacitance field-effect
      transistors.
AB  - Limited by the Boltzmann distribution of electrons, the sub-threshold swing (SS)
      of conventional MOSFETs cannot be less than 60 mV dec-1. This limitation hinders
      the reduction of power dissipation of the devices. Herein, we present high
      performance In2O3 nanowire (NW) negative capacitance field-effect transistors (NC
      FETs) by introducing a ferroelectric P(VDF-TrFE) layer in a gate dielectric
      stack. The fabricated devices exhibit excellent gate modulation with a high
      saturation current density of 550 MUA MUm-1 and an outstanding SS value less than
      60 mV dec-1 for over 4 decades of channel current. The assembled inverter circuit
      can demonstrate an impressive voltage gain of 25 and a cut-off frequency of over
      10 MHz. By utilizing the self-aligned fabrication scheme, the device can be
      ultimately scaled down to below 100 nm channel length. The devices with 200 nm
      channel length exhibit the best performances, in which a high on/off current
      ratio of >107, a large output current density of 960 MUA MUm-1 and a small SS
      value of 42 mV dec-1 are obtained at the same time. All these would not only
      evidently demonstrate the potency of NW NC-FETs to break through the Boltzmann
      limit in nanoelectronics, but also open up a new avenue to low-power transistors
      for portable products.

PMID- 30298892
TI  - Label free localization of nanoparticles in live cancer cells using spectroscopic
      microscopy.
AB  - Gold nanoparticles (GNPs) have become essential tools used in nanobiotechnology
      due to their tunable plasmonic properties and low toxicity in biological samples.
      Among the available approaches for imaging GNPs internalized by cells,
      hyperspectral techniques stand out due to their ability to simultaneously image
      and perform spectral analysis of GNPs. Here, we present a study utilizing a
      recently introduced hyperspectral imaging technique, live-cell PWS, for the
      imaging, tracking, and spectral analysis of GNPs in live cancer cells. Using
      principal components analysis, the extracellular or intracellular localization of
      the GNPs can be determined without the use of exogenous labels. This technique
      uses wide-field white light, assuring minimal toxicity and suitable signal-to
      noise ratio for spectral and temporal resolution of backscattered signal from
      GNPs and local cellular structures. The application of live-cell PWS introduced
      here could make a great impact in nanomedicine and nanotechnology by giving new
      insights into GNP internalization and intracellular trafficking.

PMID- 30298893
TI  - Ultrafast excited state dynamics of nonfluorescent cyclopheophorbide-a enol, a
      catabolite of chlorophyll-a detoxified in algae-feeding aquatic microbes.
AB  - For photosynthetic organisms that nourish the earth's biosphere, chlorophylls
      (Chls) are the major pigments utilized for light harvesting and primary charge
      separation. Although Chl molecules are effective photosensitizers, they are
      inevitably phototoxic to living organisms due to the facile generation of highly
      oxidative singlet oxygen (1O2) through triplet energy transfer from their
      photoexcited states to oxygen molecules. Such phototoxicity of Chls is a major
      problem for translucent microbes that feed on photosynthetic algae. Recently, it
      has been reported that the metabolic conversion of Chls-a/b to 132,173
      cyclopheophorbide-a/b enols (cPPB-a/bEs) is the detoxification mechanism for
      algivorous protists. cPPB-a/bEs are colored pi-conjugated cyclic tetrapyrroles
      but are nonfluorescent due to efficient nonradiative decay. In this study,
      femtosecond time-resolved transient absorption spectroscopy was applied to cPPB
      aE with the aim of understanding its quenching mechanism. As a result, we have
      captured the ultrafast generation of an intermediate state (~140 fs) that leads
      to the rapid internal conversion to the ground state (~450 fs).

PMID- 30298894
TI  - Nutritional characterization and shelf-life of packaged microgreens.
AB  - Besides the variety of colours and flavours, microgreens show interesting
      nutritional properties, mainly regarding their contents of mineral nutrients and
      bioactive compounds. To date, the literature has prevalently focused on the
      individual nutritional features of microgreens usually belonging to Brassicaceae.
      The present study reports an articulated nutritional profile of six genotypes of
      microgreens, belonging to three species and two families: chicory (Cichorium
      intybus L., Puglia's local variety 'Molfetta', CM, and cultivar 'Italico a costa
      rossa', CR) and lettuce (Lactuca sativa L. Group crispa, cultivar 'Bionda da
      taglio', LB, and 'Trocadero', LT), from Asteraceae; and broccoli (Brassica
      oleracea L. Group italica Plenk, Puglia's local variety 'Mugnuli', BM, and
      cultivar 'Natalino', BN) from Brassicaceae. All the microgreens, except LB, can
      be considered good sources of Ca, whilst LT and CM also showed considerable
      amounts of K. As regards bioactive compounds, Brassica microgreens were the
      richest in phenolic antioxidants. The microgreens also presented higher amounts
      of alpha-tocopherol and carotenoids compared to mature vegetables. In particular,
      broccoli microgreens and LB showed the highest amounts of vitamin E, while
      Asteraceae microgreens presented the highest levels of carotenoids. Due to their
      delicate tissues, fresh cut microgreens showed a shelf life not exceeding ten
      days at 5  degrees C. The results obtained highlight the possibility to exploit
      genetic biodiversity in order to obtain tailored microgreens with the desired
      nutritional profiles, with particular regard to mineral nutrients and bioactive
      compounds. Appropriate pre- and post-harvest strategies should be developed, so
      as to allow microgreens to retain as long as possible their nutritional value.

PMID- 30298895
TI  - C-Alkylation of N-alkylamides with styrenes in air and scale-up using a microwave
      flow reactor.
AB  - C-Alkylation of N-alkylamides with styrenes is reported, proceeding in ambient
      air/moisture to give arylbutanamides and pharmaceutically-relevant scaffolds in
      excellent mass balance. Various amide and styrene derivatives were tolerated,
      rapidly affording molecular complexity in a single step; thus highlighting the
      future utility of this transformation in the synthetic chemistry toolbox.
      Reaction scalability (up to 65 g h-1 product) was demonstrated using a Microwave
      Flow reactor, as the first example of a C-alkylation reaction using styrenes in
      continuous flow.

PMID- 30298896
TI  - Endothelial, smooth muscle and fibroblast cell sheet fabrication from self
      assembled thermoresponsive poly(glycidyl ether) brushes.
AB  - In this study, we introduce a platform to fabricate human dermal fibroblast
      (HDF), human aortic smooth muscle cell (HAoSMC) and human umbilical vein
      endothelial cell (HUVEC) sheets using thermoresponsive poly(glycidyl ether)
      coatings. Copolymer brushes based on glycidyl methyl ether (GME) and ethyl
      glycidyl ether (EGE) were self-assembled onto polystyrene (PS) culture substrates
      via the physical adsorption of a hydrophobic, photoreactive benzophenone anchor
      block based on the monomer 4-[2-(2,3-epoxypropoxy)ethoxy]benzophenone (EEBP). The
      directed self-assembly of well-defined, end-tethered poly(GME-ran-EGE)-block
      poly(EEBP) (PGE) brushes was achieved via the selective, EEBP-driven adsorption
      of the asymmetric block copolymer from dilute aqueous solution below its cloud
      point temperature (CPT). Subsequently, the PGE brush layers were covalently
      immobilized onto the PS surfaces by irradiation with UV light and characterized
      by ellipsometry, static water contact angle (CA) measurements and atomic force
      microscopy (AFM). We found that, by decreasing the temperature from 37 to 20 
      degrees C, the coatings undergo a pancake-to-brush transition, which triggers
      cell sheet detachment. In addition, cell culture parameters were optimized to
      allow proper adhesion and controlled detachment of confluent HDF, HAoSMC and
      HUVEC sheets, which can be applied in vascular tissue engineering.

PMID- 30298897
TI  - Tandem radical cyclization of N-methacryloyl benzamides with CBr4 to construct
      brominated isoquinolinediones.
AB  - A simple cumene (isopropylbenzene, IPB) promoted auto-oxidation involved tandem
      radical cyclization of N-methacryloyl benzamides using stable and easy-to-handle
      CBr4 as the bromine source is described. This strategy provides an efficient and
      practical approach for the synthesis of bromine containing isoquinolinediones.
      This method also presents a new way to generate bromine radicals using a mild
      auto-oxidation pathway.

PMID- 30298898
TI  - Opposed flow focusing: evidence of a second order jetting transition.
AB  - We propose a novel microfluidic "opposed-flow" geometry in which the continuous
      fluid phase is fed into a junction in a direction opposite to the dispersed
      phase. This pulls out the dispersed phase into a micron-sized jet, which decays
      into micron-sized droplets. As the driving pressure is tuned to a critical value,
      the jet radius vanishes as a power law down to sizes below 1 MUm. By contrast,
      the conventional "coflowing" junction leads to a first order jetting transition,
      in which the jet disappears at a finite radius of several MUm, to give way to a
      "dripping" state, resulting in much larger droplets. We demonstrate the
      effectiveness of our method by producing the first microfluidic silicone oil
      emulsions with a sub micron particle radius, and utilize these droplets to
      produce colloidal clusters.

PMID- 30298899
TI  - 3-Arm star pyrene-functional PMMAs for efficient exfoliation of graphite in
      chloroform: fabrication of graphene-reinforced fibrous veils.
AB  - 3-Arm PMMAs end-functionalized by pyrene were designed as dispersing/stabilizing
      agents for the liquid-phase exfoliation of graphite in low-boiling point solvents
      like chloroform. The synthetic procedure comprised ARGET ATRP controlled
      polymerization, click chemistry and the quaternization reaction of triazole,
      ensuring tailor-made, well-defined pyrene-functional star PMMAs. Among a series
      of different pyrene-functional macromolecular topologies, the (PMMA-py2)3 proved
      the most efficient exfoliation agent giving relatively high graphene
      concentration (0.36 mg ml-1) at exceptionally low polymer/graphite mass ratio
      (mP/mGF = 0.003) and short sonication time (3 h). A 5-cycle iterative procedure
      relying on the redispersion of the sediment was developed yielding CG = 1.29 mg
      ml-1 with 14.8% exfoliation yield, under the favorable conditions of 10.5 h total
      shear mixing/tip sonication time and overall mP/mGF ratio as low as 0.15. In
      parallel, all-atom molecular dynamics simulations were conducted which helped
      understand the mechanism by which pyrene-functional macromolecular topologies act
      as efficient dispersing agents of graphene. Finally the G@(PMMA-Py)3 hybrids were
      well dispersed into the PMMA matrix by electrospinning to fabricate graphene
      based nanocomposite fibrous veils. These graphene/polymer nanocomposites
      exhibited enhanced stiffness and strength by a factor of 4.4 with 1.5 wt%
      graphene hybrids as nanofillers.

PMID- 30298900
TI  - Structurally tunable plasmonic absorption bands in a self-assembled nano-hole
      array.
AB  - In this paper, we demonstrate a theoretical and experimental study on a nano-hole
      array that can realize perfect absorption in the visible and near-infrared
      regions. The absorption spectrum can be easily controlled by adjusting the
      structural parameters including the radius and period of the nano-hole, and the
      maximal absorption can reach 99.0% in theory. In order to clarify the physical
      mechanism of the absorber, we start from the extraordinary optical transmission
      supported by the nano-hole array in a thin metallic film coated on a glass
      substrate, and then analyse the perfect absorption in the metal-insulator-metal
      structure. The surface plasmon modes supported by the nano-hole array are
      completely clarified and both the FDTD simulation and waveguide theory are used
      to help us understand the physical mechanism, which can provide a new perspective
      in designing this kind of perfect absorber. In addition, the nano-hole array can
      be fabricated by simple and low-cost nanosphere lithography, which makes it a
      more appropriate candidate for spectroscopy, photovoltaics, photodetectors,
      sensing, and surface enhanced Raman scattering.

PMID- 30298901
TI  - Personalized Goal Attainment in Dementia Care: Measuring What Persons with
      Dementia and Their Caregivers Want.
AB  - OBJECTIVES: To develop a process of goal-setting and measurement of goal
      attainment in a dementia care management program. DESIGN: Observational. SETTING:
      Dementia care management program in an urban academic medical center.
      PARTICIPANTS: Persons with dementia (N=101) and their caregivers; nurse
      practitioner dementia care managers (N=5). INTERVENTION: Specification of a
      personalized health goal and action plan and measurement of goal attainment using
      goal attainment scaling in a clinical care visit. MEASUREMENTS: Goal attainment
      at 6 and 12 months; focus groups of 5 dementia care managers. RESULTS: Eighty
      four percent of participant goals were nonmedical, 47% were related to quality of
      life, and 29% were caregiver support goals. Eighty-eight percent of participants
      felt that the goal they set was meaningful and 74% that the goal-setting process
      captured something different from usual care, and 85% found the process helpful
      in planning for future care. At 6 months, 74% of dyads had achieved or exceeded
      their expected level of goal attainment. Dementia care managers felt that the
      goal-setting process improved their understanding of what was most important to
      the patient, helped set expectations about disease progression and care needs,
      and provided positive reinforcement when goals were accomplished and an
      opportunity for revision when goals were not met. CONCLUSION: Goal setting using
      goal attainment scaling can be incorporated into the care of persons with
      dementia to establish and attain person-centered goals. Research is needed to
      further develop personalized goal attainment as an outcome measure for dementia
      care. J Am Geriatr Soc 66:2120-2127, 2018.

PMID- 30298902
TI  - Smoking Cessation Aids Alone Do Not Help Smokers Quit.

PMID- 30298903
TI  - Treatment of mycosis fungoides and Sezary syndrome with romidepsin: a series of
      32 cases of the French Study Group for Cutaneous Lymphoma.
AB  - Treatment of cutaneous T-cell lymphoma is based on skin-directed therapies for
      early stage disease and systemic therapies for advanced stage disease. Romidepsin
      (Istodax(c)) is a histone deacetylase inhibitor approved by the FDA, after two
      phase II pivotal studies for the treatment of Mycosis Fungoides (MF) and Sezary
      Syndrome (SS) after at least one prior line of systemic therapy1,2 . In France,
      romidepsin is only available on Authorization for Temporary Use. Until now, few
      data are available as to its use in real life. This article is protected by
      copyright. All rights reserved.

PMID- 30298904
TI  - TGF-beta suppresses RasGRP1 expression and supports regulatory T cell resistance
      against p53-induced CD28-dependent T-cell apoptosis.
AB  - Thymus-derived regulatory T cells (tTregs) play pivotal roles in immunological
      self-tolerance and homeostasis. A majority of tTregs are reactive to self
      antigens and are constantly exposed to antigenic stimulation. Despite this
      continuous stimulation, tTreg and conventional T-cell populations remain balanced
      during homeostasis, but the mechanisms controlling this balance are unknown. We
      previously reported a form of activation-induced cell death, which is dependent
      on p53 (p53-induced CD28-dependent T-cell apoptosis, PICA). Under PICA-inducing
      conditions, tTregs survive while a majority of conventional T cells undergo
      apoptosis, suggesting there is a survival mechanism that protects tTregs. Here,
      we report that the expression of RasGRP1 (Ras guanyl-releasing protein 1) is
      required for PICA, as conventional T cells isolated from RasGRP1-deficient mice
      become resistant to PICA. After continuous stimulation, tTregs express a
      substantially lower amount of RasGRP1 compared to conventional T cells. This
      reduced expression of RasGRP1 is dependent on TGF-beta, as addition of TGF-beta
      to conventional T cells reduces RasGRP1 expression. Conversely, RasGRP1
      expression in tTregs increases when TGF-beta signaling is inhibited. Together,
      these data show that RasGRP1 expression is repressed in tTregs by TGF-beta
      signaling and suggests that reduced RasGRP1 expression is critical for tTregs to
      resist apoptosis caused by continuous antigen exposure.

PMID- 30298905
TI  - Model-assisted process characterization and validation for a continuous two
      column protein A capture process.
AB  - In this study we introduce three process characterization approaches toward
      validation of continuous twin-column capture chromatography (CaptureSMB),
      referred to as "standard," "model assisted," and "hybrid." They are all based on
      a traditional risk-based approach, using process description, risk analysis,
      design-of-experiments (DoE), and statistical analysis as essential elements. The
      first approach, the "standard" approach uses a traditional experimental DoE to
      explore the design space of the high-ranked process parameters for the continuous
      process. Due to the larger number of process parameters in the continuous
      process, the DoE is extensive and includes a larger number of experiments than an
      equivalent DoE of a single column batch capture process. In the investigated
      case, many of the operating conditions were practically infeasible, indicating
      that the design space boundaries had been chosen inappropriately. To reduce
      experimental burden and at the same time enhance process understanding, an
      alternative "model assisted" approach was developed in parallel, employing a
      chromatographic process model to substitute experimental runs by computer
      simulations. Using the "model assisted" approach only experimental conditions
      that were feasible in terms of process yield constraints (>90%) were considered
      for statistical analysis. The "model assisted" approach included an optimization
      part that identified potential boundaries of the design space automatically. In
      summary, the "model assisted" approach contributed to increased process
      understanding compared to the "standard" approach. In this study, a "hybrid"
      approach was also used containing the general concepts of the "standard" approach
      but substituting a number of its experiments by computer simulations. The
      presented approaches contain essential elements of the Food and Drug
      Administration's process validation guideline.

PMID- 30298906
TI  - The prognostic value of 3 commonly measured blood parameters and geriatric
      assessment to predict overall survival in addition to clinical information in
      older patients with cancer.
AB  - BACKGROUND: The current study was performed to evaluate the prognostic value of
      laboratory parameters and geriatric assessment (GA) in addition to a baseline
      model with clinical information regarding overall survival (OS) in patients with
      cancer. METHODS: GA was systematically performed in patients aged >=70 years. The
      baseline model consisted of age, tumor type, and stage of disease. The
      incremental prognostic values of the GA as a whole (10-item GA) and laboratory
      parameters were assessed separately and combined. The parameters included
      hemoglobin (Hb), albumin, C-reactive protein (CRP), and the Glasgow Prognostic
      Score (GPS). Analyses were conducted with continuous and dichotomized variables.
      Cox models were compared based on Akaike information criterion (DeltaAIC) and
      their discriminatory ability was assessed using the concordance probability
      estimate (CPE). RESULTS: A total of 328 patients were considered for this
      analysis. The baseline model had a CPE of 0.725. The addition of CRP, albumin,
      and Hb combined resulted in the best performing model (DeltaAIC: 40.12 and CPE:
      0.757) among the laboratory parameters. However, the 10-item GA improved the
      baseline model even more (DeltaAIC: 46.03 and CPE: 0.769). Similar results were
      observed in the analysis with dichotomous variables. The addition of the 3
      laboratory parameters (CRP, albumin, and Hb) improved the CPE by 1.4% compared
      with the baseline model already extended with the 10-item GA. The CPE increase
      (1.7%) was the highest with the GPS in the analysis with dichotomous variables.
      CONCLUSIONS: GA appears to add slightly more prognostic information than
      laboratory parameters in addition to clinical information. The laboratory
      parameters have an additional prognostic value beyond clinical and geriatric
      information.

PMID- 30298907
TI  - Tuberous sclerosis-associated neuropsychiatric disorders: a paediatric cohort
      study.
AB  - AIM: We aimed to study tuberous sclerosis-associated neuropsychiatric disorders
      (TAND) in children and adolescents with tuberous sclerosis complex (TSC). METHOD:
      Retrospective and prospective cohort study conducted at a Paediatric Neurology
      Unit of an Italian Tertiary Care Hospital. Clinical and neuroimaging data were
      reviewed. Scores for neurological and epilepsy outcomes (Extended Glasgow Outcome
      Scale, Paediatric Version and Early Childhood Epilepsy Severity Scale modified),
      semi-structured interviews (authorized Italian version of the TAND checklist and
      Vineland Adaptive Behavior Scales) and questionnaires (Child Behavior Checklist
      [CBCL]) were applied at last follow-up. RESULTS: Thirty-two patients with TSC
      (age range 1-19y) were enrolled. Eighty-eight per cent had at least one TAND and
      47% had intellectual disability. The TAND checklist showed internalizing problems
      in 25.8% of cases (vs 41.9% by CBCL), and externalizing problems in 41.9% (vs
      9.7% by CBCL). TAND prevailed in patients with de novo mutation of TSC2, high
      tuber load, and severe neurological and epilepsy outcomes. INTERPRETATION: In our
      cohort, 78% of patients had more than four TAND behavioural problems;
      nevertheless, they did not show a constant and specific neuropsychiatric profile.
      Clinical, neurophysiological, and neuroradiological features were associated with
      several TAND. The TAND checklist appeared more effective than the CBCL,
      particularly in detecting externalizing problems. WHAT THIS PAPER ADDS: The
      Tuberous sclerosis-associated neuropsychiatric disorders (TAND) checklist is an
      effective tool for TAND screening. The TAND checklist helps define
      psychopathological and neuropsychiatric aspects in paediatric patients with
      Tuberous sclerosis complex (TSC). TAND were found in 88% of patients with TSC,
      whilst 78% had more than four TAND. TAND distribution depends on different
      clinical and neuroradiological features.

PMID- 30298908
TI  - Trophoblast-endothelium signaling involves angiogenesis and apoptosis in a
      dynamic bioprinted placenta model.
AB  - Trophoblast invasion and remodeling of the maternal spiral arteries are required
      for pregnancy success. Aberrant endothelium-trophoblast crosstalk may lead to
      preeclampsia, a pregnancy complication that has serious effects on both the
      mother and the baby. However, our understanding of the mechanisms involved in
      this pathology remains elementary because the current in vitro models cannot
      describe trophoblast-endothelium interactions under dynamic culture. In this
      study, we developed a dynamic three-dimensional (3D) placenta model by
      bioprinting trophoblasts and an endothelialized lumen in a perfusion bioreactor.
      We found the 3D printed perfusion bioreactor system significantly augmented
      responses of endothelial cells by encouraging network formations and expressions
      of angiogenic markers, cluster of differentiation 31 (CD31), matrix
      metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9), and vascular
      endothelial growth factor A (VEGFA). Bioprinting favored colocalization of
      trophoblasts with endothelial cells, similar to in vivo observations. Additional
      analysis revealed that trophoblasts reduced the angiogenic responses by reducing
      network formation and motility rates while inducing apoptosis of endothelial
      cells. Moreover, the presence of endothelial cells appeared to inhibit
      trophoblast invasion rates. These results clearly demonstrated the utility and
      potential of bioprinting and perfusion bioreactor system to model trophoblast
      endothelium interactions in vitro. Our bioprinted placenta model represents a
      crucial step to develop advanced research approach that will expand our
      understanding and treatment options of preeclampsia and other pregnancy-related
      pathologies.

PMID- 30298909
TI  - Beliefs About Moral Obligation Structure Children's Social Category-Based
      Expectations.
AB  - Young children view social category members as morally obligated toward one
      another, and expect these obligations to shape people's social behavior. The
      present work investigates how children specify which behaviors are constrained by
      social categories in this way. In two studies (N = 128), 4- and 5-year-old
      children predicted that morally positive behaviors would be directed toward in
      group members, and that morally negative behaviors would be directed toward out
      group members, but did not hold equally strong expectations about behaviors
      described as positive or negative for reasons irrelevant to morality. Thus,
      notions of morality are embedded within children's representations of social
      categories, such that when learning about novel moral norms, children immediately
      expect those obligations to uniquely hold within social groups.

PMID- 30298910
TI  - Early Literacy Predictors and Second-Grade Outcomes in Children Who Are Hard of
      Hearing.
AB  - This study contrasted the early literacy outcomes of children who are hard of
      hearing (CHH) with children with normal hearing (CNH). At age 5, prereading
      skills of oral language, phonological processing, and print knowledge were
      examined in CHH (N = 180) and CNH (N = 80). The CHH had poorer oral language and
      phonological processing abilities than the CNH but comparable knowledge of print.
      At age 8, measures of word reading, and reading comprehension yielded no
      differences between CHH (N = 108) and CNH (N = 62) except for reading
      comprehension for the moderately severe CHH. Reading achievement in CHH was found
      to exceed predictions based on prereading performance. This resilience was
      associated with gains in oral language during the early school years.

PMID- 30298912
TI  - The evolution of epigenetically mediated adaptive transgenerational plasticity in
      a subdivided population.
AB  - Transgenerational plasticity (TGP) occurs when offspring exhibit plasticity in
      traits induced by the environments experienced by their parents, and represents a
      nongenetic mechanism of inheritance. Evidence that traits can be transmitted to
      future generations by means other than genetic inheritance has caused a surge of
      interest in epigenetic inheritance, but evidence for epigenetic modifications
      being both adaptive and heritable remains scarce. What features would make a
      species most prone to evolve a system of epigenetically mediated adaptive TGP?
      Here, we use population-genetic models modified to include epigenetic induction
      and inheritance to investigate if and when epigenetically mediated adaptive TGP
      would be expected to evolve for a population subdivided between two habitats
      connected by migration. We show that differences in the direction of selection
      between the two habitats drives the evolution of epigenetically mediated adaptive
      TGP. With low migration, the strength of indirect selection in favor of
      epigenetically mediated adaptive TGP increases with migration rate. Yet, with
      higher migration, the opposite trend is observed. We predict that species
      subdivided between habitats that differ in the direction of selection with
      moderate migration rates between the habitats would be most likely to evolve
      epigenetically mediated adaptive TGP if costs of producing such systems are not
      too high.

PMID- 30298913
TI  - A genotypic trade-off between constitutive resistance to viral infection and host
      growth rate.
AB  - Genotypic trade-offs are fundamental to the understanding of the evolution of
      life-history traits. In particular, the evolution of optimal host defense and the
      maintenance of variation in defense against infectious disease is thought to be
      underpinned by such evolutionary trade-offs. However, empirical demonstrations of
      these trade-offs that satisfy the strict assumptions made by theoretical models
      are rare. Additionally, none of these trade-offs have yet been shown to be
      robustly replicable using a variety of different experimental approaches to rule
      out confounding issues with particular experimental designs. Here, we use inbred
      isolines as a novel experimental approach to test whether a trade-off between
      viral resistance and growth rate in Plodia interpunctella, previously
      demonstrated by multiple selection experiments, is robust and meets the strict
      criteria required to underpin theoretical work in this field. Critically, we
      demonstrate that this trade-off is both genetic and constitutive. This finding
      helps support the large body of theory that relies on these assumptions, and
      makes this trade-off for resistance unique in being replicated through multiple
      experimental approaches and definitively shown to be genetic and constitutive.

PMID- 30298914
TI  - Open or close the door to the outgroup? Diversity beliefs moderate the impact of
      group boundary permeability on attitudes toward the outgroup.
AB  - The present research investigated the moderating role of diversity beliefs with
      the aim of reconciling inconsistent findings regarding the impact of group
      boundary permeability on attitudes toward outgroup. In Study 1, all variables
      were measured with self-report scales completed by Chinese participants. In Study
      2, diversity beliefs were manipulated by randomly assigning Chinese participants
      to a high or low diversity belief condition. In Study 3, we replicated the
      moderating model with American participants. Results of all three studies
      indicated that diversity beliefs moderated the relationship between group
      boundary permeability and attitudes toward outgroup. Individuals with high
      diversity beliefs held more positive attitudes toward the outgroup when the group
      boundary was permeable (vs. impermeable). Conversely, individuals with low
      diversity beliefs held more negative attitudes toward the outgroup when the group
      boundary was permeable (vs. impermeable). These findings suggest that when the
      inflow of the outgroup members is inevitable, attitudes toward the outgroup may
      be effectively improved by increasing diversity beliefs.

PMID- 30298911
TI  - Immune cells in the tumour: new routes of retinoids for chemoprevention and
      chemotherapeutics.
AB  - Retinoids, vitamin A and its natural and synthetic analogues have various
      functions, including being involved in cell proliferation and differentiation and
      participating in the formation of vertebrate morphology. In addition, they may
      activate certain tumour suppressor genes that then act as tumour inhibitors. In
      the past decades, retinoids have been regarded as promising chemotherapeutic and
      chemopreventive agents; however, their mechanisms are still not fully understood.
      Immune cells that participate in or are associated with the immune response play
      vital roles in the initiation and development of many cancers. Interestingly,
      recent studies have demonstrated that retinoids can also exert various effects on
      immune cells including macrophages, T cells and dendritic cells in tumour tissues
      to execute anti-tumour actions, providing new insights into chemoprevention and
      chemotherapeutics. In this review, we focus on the effects of retinoids on immune
      cells in the tumour, which may provide new approaches for antineoplastic
      strategies.

PMID- 30298915
TI  - Accuracy of anogenital distance and anti-Mullerian hormone in the diagnosis of
      endometriosis without surgery.
AB  - OBJECTIVE: To assess the predictive ability of a combination of anogenital
      distance (AGD) and anti-Mullerian hormone (AMH) to diagnosis the presence of
      endometriosis without surgery. METHODS: The present study included women
      diagnosed with endometriosis and a control group who attended the "Virgen de la
      Arrixaca" University Hospital, Murcia, Spain, between September 1, 2014, and May
      31, 2015. Serum concentrations of AMH were measured, and two AGD measurements
      were obtained: from the anterior clitoral surface to the upper verge of the anus
      (AGDAC ), and from the posterior fourchette to the upper verge of the anus (AGDAF
      ). Data were assessed by receiver operator characteristic (ROC) curves. RESULTS:
      Women in the endometriosis group (n=57) had significantly shorter AGDAF (22.8 +/-
      4.6 vs 27.2 +/- 5.7 mm; P<0.001) and lower AMH (2.2 +/- 2.5 vs 3.3 +/- 1.9 ng/mL;
      P<0.003) compared with the control group (n=93). Women with serum AMH below the
      clinical cut-off (1 ng/mL) were 17.40-times more likely to have endometriosis
      (95% confidence interval [CI] 5.64-53.82). The area under the ROC curve of
      combined AMH and AGDAF was 0.77 (95% CI 0.70-0.85). CONCLUSION: The model for
      predicting endometriosis on the basis of AMH and AGD could be useful for
      clinicians and epidemiologists to improve diagnosis and prognosis of this
      condition.

PMID- 30298916
TI  - PTSD and the influence of context: The self as a social mirror.
AB  - The principal accepted models of posttraumatic stress disorder (PTSD) are based
      on both memory processing and biological/brain changes occurring when one's life
      or well-being is threatened. It is our thesis that these models would be greatly
      informed by community studies indicating that PTSD is predicted to a greater
      extent by earlier life experience and experiences that occur distant from the
      threatening event. These findings suggest posttraumatic responding is best
      conceptualized through the lens of the self-in-context, as opposed to imprinting
      that results from a given event at a given time. Moreover, studies of non-Western
      populations often do not express trauma as PTSD, or at least not primarily as
      PTSD, which argues against specific neural or memory encoding processes, but
      rather for a more plastic neural process that is shaped by experience and how the
      self develops in its cultural context, as a product of a broad array of
      experiences. We posit that fear and emotional conditioning as well as the ways
      traumas are encoded in memory are only partial explanatory mechanisms for trauma
      responding, and that issues of safety and harm, which are long term and
      developmental, are the common and principal underpinnings of the occurrence of
      posttraumatic distress, including PTSD.

PMID- 30298917
TI  - Digest: The guppy project: Predicting evolution in the wild.

PMID- 30298918
TI  - Digest: The importance of genital morphology in Drosophila copulation.
AB  - Drosophila is a common model organism in the study of reproductive isolation. In
      their 2018 work, Tanaka et al. used introgression to substitute D. mauritiana
      genomic segments into a D. simulans genetic background, creating lines with
      modified genital structures. These changes were found to significantly alter the
      copulation duration and motility of mating pairs by influencing genital coupling.

PMID- 30298919
TI  - Delivering baking soda to the brain.

PMID- 30298920
TI  - Case series showing the efficacy of 5-aminolaevulinic acid photodynamic therapy
      for epidermal growth factor receptor inhibitor-induced paronychia and pyogenic
      granuloma-like lesions.

PMID- 30298921
TI  - Context-dependent interactions between pathogens and a mutualist affect pathogen
      fitness and mutualist benefits to hosts.
AB  - Plants and animals host many microbial symbionts, including both pathogens and
      mutualists. However, most experimental studies include only one symbiont, and few
      examine interactions of more than two microbes with their host. Here, we examined
      whether coinfection with two pathogens causes a synergistic reduction in the
      benefits that hosts receive from a microbial mutualist. We also measured the
      effects of a microbial mutualist on the within- and between-host competition
      between coinfecting pathogens. We manipulated the presence of Clover yellow vein
      virus (ClYVV), Bean common mosaic virus (BCMV), rhizobia bacteria, and nitrogen
      fertilizer in common beans (Phaseolus vulgaris). We found asymmetric, context
      dependent interactions among the three microbial symbionts and their host.
      Coinfection with both viruses led to greater than additive negative effects on
      the amount of nitrogen that plants received from rhizobia. Rhizobia colonization
      decreased immune signaling in singly infected plants, but not in coinfected
      plants. Compared to single ClYVV infection, ClYVV reached higher concentrations
      within hosts coinfected with BCMV, but only in the presence of rhizobia.
      Coinfection increased BCMV vertical transmission rates for plants without
      supplemental nitrogen, but overall vertical transmission opportunities were not
      affected due to reduced seed production. Examining interactions between multiple
      microbes sharing a host can reveal important insights about nutrient cycling,
      disease severity, and pathogen epidemiology.

PMID- 30298922
TI  - How do international lawyers handle facts? The role of folk sociological theories
      at the International Criminal Court.
AB  - The International Criminal Court (ICC) investigates international crimes
      committed in different parts of the world. Earlier scholarly analysis of the work
      performed by the ICC judges has pointed out that judges often lack cultural and
      national understanding of the local norms and customs of regions where defendants
      come from. This article treats this lack of contextual knowledge displayed by the
      court as a case of structural ignorance rather than an aberration to be 'exposed'
      or censured. International lawyers indeed must ground their legal narratives with
      plausible sociological explanations of contextual elements to overcome their lack
      of familiarity with the field and the scarcity of their investigative resources.
      By uncovering the role of 'folk sociological theories' (FSTs) in the
      establishment of facts in a court context, this article addresses the debate over
      the efficiency of international criminal justice by highlighting the need to
      bring historical truth back in. The empirical evidence is based on several years
      of participant observation in the ICC during the trials against Mathieu Ngudjolo
      and Germain Katanga, two militiamen from the Democratic Republic of Congo (DRC).

PMID- 30298923
TI  - Dietary material properties shape cranial suture morphology in the mouse
      calvarium.
AB  - Cranial sutures are fibrous connective tissue articulations found between
      intramembranous bones of the vertebrate cranium. Growth and remodeling of these
      tissues is partially regulated by biomechanical loading patterns that include
      stresses related to chewing. Advances in oral processing structure and function
      of the cranium that enabled mammalian-style chewing is commonly tied to the
      origins and evolution of this group. To what degree masticatory overuse or
      underuse shapes the complexity and ossification around these articulations can be
      predicted based on prior experimental and comparative work. Here, we report on a
      mouse model system that has been used to experimentally manipulate dietary
      material properties in order to investigate cranial suture morphology.
      Experimental groups were fed diets of contrasting material properties. A
      masticatory overuse group was fed pelleted rodent chow, nuts with shells, and
      given access to cotton bedding squares. An underuse group was deprived of cotton
      bedding as well as diverse textured food, and instead received gelatinized food
      continuously. Animals were raised from weaning to adulthood on these diets, and
      sagittal, coronal and lambdoid suture morphology was compared between groups.
      Predicted intergroup variation was observed in mandibular corpus size and
      calvarial suture morphology, suggesting that masticatory overuse is associated
      with jaw and suture growth. The anterior region of the sagittal suture where it
      intersects with the coronal suture (bregma) showed no effect from the experiment.
      The posterior sagittal suture where it intersects with the lambdoid sutures
      (lambda) was more complex in the overuse group. In other words, the posterior
      calvarium was responsive to dietary material property demands while the anterior
      calvarium was not. This probably resulted from the different strain magnitudes
      and/or strain frequencies that occurred during overuse diets with diverse
      material properties as compared with underuse diets deprived of such enrichment.
      This work highlights the contrasting pattern of the sutural response to loading
      differences within the calvarium as a result of diet.

PMID- 30298925
TI  - The strength of sex-specific selection in the wild.
AB  - Anisogamy predisposes the sexes to very different patterns of selection on shared
      traits. Selective differences between the sexes may manifest as changes in the
      direction or strength of selection acting on shared phenotypes. Although previous
      studies have found evidence for widespread differences in the direction of
      selection between the sexes, surprisingly little is known regarding potential
      differences in the magnitude of selection and whether such differences might be
      confined to specific components of fitness. We conducted a meta-analysis using
      865 estimates of phenotypic selection from wild populations to characterize sex
      differences in the strength of selection and to ask whether different components
      of fitness exhibit differences in sex bias in the strength of selection. Overall,
      consistent with past results, we find evidence of male bias in the strength of
      selection, driven primarily by components of fitness related to mating success
      and we discuss several evolutionary implications.

PMID- 30298924
TI  - The Impact of Healthcare-Associated Methicillin-Resistant Staphylococcus aureus
      Infections on Postdischarge Health Care Costs and Utilization across Multiple
      Health Care Systems.
AB  - OBJECTIVE: To measure how much of the postdischarge cost and utilization
      attributable to methicillin-resistant Staphylococcus aureus (MRSA) health care
      associated infections (HAIs) occur within the US Department of Veterans Affairs
      (VA) system and how much occurs outside. DATA SOURCES/STUDY SETTING: Health care
      encounters from 3 different settings and payment models: (1) within the VA; (2)
      outside the VA but paid for by the VA (purchased care); and (3) outside the VA
      and paid for by Medicare. STUDY DESIGN: Historical cohort study using data from
      admissions to VA hospitals between 2007 and 2012. METHODS: We assessed the impact
      of a positive MRSA test result on costs and utilization during the 365 days
      following discharge using inverse probability of treatment weights to balance
      covariates. PRINCIPAL FINDINGS: Among a cohort of 152,687 hospitalized Veterans,
      a positive MRSA test result was associated with an overall increase of 6.6 (95
      percent CI: 5.7-7.5) inpatient days and $9,237 (95 percent CI: $8,211-$10,262)
      during the postdischarge period. VA inpatient admissions, Medicare
      reimbursements, and purchased care payments accounted for 60.6 percent, 22.5
      percent, and 16.9 percent of these inpatient costs. CONCLUSIONS: While most of
      the excess postdischarge health care costs associated with MRSA HAIs occurred in
      the VA, non-VA costs make up an important subset of the overall burden.

PMID- 30298926
TI  - Bond paths between distant atoms do not necessarily indicate dominant
      interactions.
AB  - The goal of the article is to revive discussion on the interpretation of bond
      paths linking distant atoms, particularly tracing weak interactions in dimers.
      According to the Pendas' concept of privileged exchange channel, a bond path is
      formed between this pair of competing atoms, which is associated with larger
      value of the exchange energy. We point out that, due to the short-range nature of
      the exchange energy, bond paths linking distant atoms clearly become doubtful
      indicators of dominant intermolecular interactions, particularly if some other
      characteristics (geometric, spectroscopic, based on electrostatic parameters,
      etc.) indicate other intermolecular interactions as dominant. Several such cases
      are thoroughly investigated. We show that electrostatic parameters are much more
      reliable indicators of dominant intermolecular interactions than bond paths.
      Then, we pay attention that the presence of ("unexpected", i.e., not necessarily
      indicating dominant intermolecular interactions) bond paths between pairs of
      atoms featuring highly expanded charge distributions can be easily explained by
      visual exploration of isodensity contour plots. As always pointing in the
      direction of the steepest increase, the gradient vector of the electron density
      favors areas of its high values gaining higher exchange energy, yet being blind
      to highly electron deficient areas nearby, which, however, can quite often be
      involved in dominant intermolecular interactions as strongly suggested by many
      other bonding analysis. We also suggest that an interatomic component of Hellmann
      Feynman force would most likely be the most reliable indicator of attractive or
      repulsive character of individual interatomic interaction. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30298927
TI  - The capacity of the BATCH as a predictive tool for discharge planning for people
      with neuropsychiatric disorders.
AB  - BACKGROUND/AIM: Assessment of cognitive function in people with neurosychiatric
      disorders can be challenging, due to behavioural and psychiatric symptomatology.
      The Behavioural Assesment Tool for Cognition and Higher Functioning (BATCH) is a
      validated observational tool that complements formal cognitive testing in this
      patient population. This study aimed to determine the capacity of the BATCH as a
      predictive tool for discharge planning. METHOD: BATCH scores for 330 consecutive
      admissions for assessment to a specialist neuropsychiatry unit between 2007 and
      2015 were analysed. The variables of interest included discharge destination,
      diagnosis, length of stay, age at discharge and BATCH scores (both subdomain and
      total). Significant predictors of discharge destination were identified using
      logistic regression analysis. RESULTS: After adjusting for age at discharge,
      three variables were found to be significant predictors of discharge destination 
      length of stay, diagnosis, and BATCH total score. The odds of being discharged
      to a destination other than home decreased by 3% for each additional BATCH total
      score unit. The length of stay remained a significant predictor of discharge
      destination when adjusting for BATCH total score, age at admission and diagnosis.
      CONCLUSION: BATCH total scores, but not subdomain scores, were predictive of
      discharge destination, along with the patients' length of stay and diagnosis.
      Knowledge of this relationship may guide clinical discharge planning, when
      working with the complex needs of this group of patients. A larger study is
      indicated to determine the range and cut-off scores for discharge destinations
      other than home.

PMID- 30298928
TI  - Longer storage of red blood cells does not affect mortality in transfused liver
      transplant recipients.
AB  - BACKGROUND: The characteristics of red blood cell (RBC) products change after 2
      weeks of cold storage. It is unclear whether older RBCs affect mortality after
      liver transplantation. This retrospective cohort study aimed to evaluate the
      association between the age of transfused RBCs and death after living donor liver
      transplantation (LDLT). STUDY DESIGN AND METHODS: Of 200 recipients who underwent
      LDLT, 118 who received RBCs with a mean storage duration of less than 10 days
      (shorter storage group) were compared with 82 with an RBC mean storage duration
      of more than 14 days (longer storage group). Key exclusion criteria were
      transfusion of very fresh RBCs stored for less than 4 days and transfusion of old
      RBCs in recipients of the shorter storage group. The primary outcome was
      posttransplant overall death. Survival analysis was performed using the Cox
      model. RESULTS: Mean RBC storage duration was 7 days in the shorter storage group
      and 17 days in the longer storage group. Death probability at 1, 2, and 5 years
      posttransplant was 5.1%, 7.6%, and 13.6% in the shorter storage group,
      respectively, and 6.1%, 8.5%, and 13.5% in the longer storage group. Death risk
      was comparable between the two groups in univariable (hazard ratio [HR] 1.00, 95%
      confidence interval [CI], 0.47-2.16, p = 0.991) and multivariable (HR 1.07, 95%
      CI, 0.46-2.50, p = 0.882) analyses. Graft failure risk was also comparable (HR
      1.04, 95% CI, 0.50-2.18, p = 0.916). Hepatocellular carcinoma recurrence
      probability at 1, 2, and 5 years was 10.8%, 15.4%, and 23.1%, respectively, in
      the shorter storage group and 11.4%, 15.9%, and 20.7% in the longer storage group
      (HR 0.84, 95% CI, 0.37-1.89, p = 0.670). No significant differences were observed
      regarding graft regeneration/function, vascular/biliary complications, acute
      kidney injury, surgical site infection, or rejection (p > 0.05). CONCLUSIONS: No
      evidence was found that transfusion of old RBCs contributes to death after LDLT.

PMID- 30298929
TI  - What are the attributes of excellence in an acute practice occupational
      therapist?
AB  - BACKGROUND/AIM: There is anecdotal recognition within the profession that novice
      occupational therapists who perform well at interview do not necessarily make the
      best practising clinicians. Further anecdotal evidence suggests that it is
      difficult to tell (at interview) which occupational therapists will follow which
      path and whether further training can achieve excellence in existing staff. What
      is it that makes the difference? What attributes do those truly 'excellent'
      clinicians have that makes them better than others? METHOD: A two-round Delphi
      survey was utilised and 18 expert occupational therapists were purposively
      recruited from Perth's three adult tertiary hospitals. Panellists rated and
      ranked sixteen possible attributes that could comprise excellence in an acute
      practice occupational therapist. RESULTS: The final order of importance (from
      most to least) of the 16 possible attributes of excellence was determined.
      Communication, Self-management and Critical Thinking were found to be the three
      most important attributes, whereas Humility was considered the least important
      attribute. All attribute rankings achieved at least a low level of consensus.
      CONCLUSION: We now have a much clearer picture of what excellence looks like in
      the acute practice setting, giving managers a new understanding. There is now the
      possibility of integrating this information into both the recruitment of new
      staff and the professional development of existing staff. In this way we can move
      forward to a future that includes the active development of occupational therapy
      excellence in ways that were not possible before these results were available.

PMID- 30298930
TI  - Internationally educated occupational therapists transitioning to practice in
      Canada: A qualitative study.
AB  - BACKGROUND/AIM: While internationally educated occupational therapists (IEOTs)
      may assist Western countries in addressing workforce shortages, their transition
      to practice can be difficult. Provincial and national levels of government in
      Canada have funded initiatives to address the barriers experienced by IEOTs. The
      purpose of this study is to identify the key forces shaping the experiences of
      IEOTs transitioning to practice in Canada. METHODS: An interpretive description
      approach was taken to interview 11 IEOTs who graduated from the Occupational
      Therapy Examination and Practice Preparation (OTepp) program. Data analysis was
      guided by the theoretical scaffolding of the occupational therapy profession. Two
      team members, who are also occupational therapists, developed codes and
      categories independently and then through discussion reached a higher level of
      interpretation. RESULTS: The experiences of IEOTs in Canada were shaped by two
      key forces: Realising that more than exam preparation is required and the impact
      of previous person, environment and occupation transactions. Participants
      underestimated their learning needs related to their transition to Canadian
      practice. As they engaged in the OTepp program, they realised that their learning
      extended beyond that required for the national certification exam. Also, the
      extent to which the participant (person), previous context (environment) and
      previous practice (occupation) were similar to Canadian therapists, influenced
      IEOTs' performance in OTepp and their overall transition to practice. The Person
      Environment-Occupation (PEO) model provided a framework to contextualise this
      theme. CONCLUSION: IEOTs will benefit from individualised learning needs
      assessments and education plans to address their specific needs. At an
      international level, the occupational therapy profession must engage in dialogue
      about the differences between education programs and the resulting implications
      for the profession. More research is also needed to understand the experiences of
      IEOTs who withdraw from or do not engage in formal supports.

PMID- 30298931
TI  - Synergistic antibacterial effects of Buddleja albiflora metabolites with
      antibiotics against Listeria monocytogenes.
AB  - Some plants of Buddleja genus possessed antimicrobial activity. In this study,
      the antibacterial activities of nine compounds from Buddleja albiflora were
      evaluated against Listeria monocytogenes, Staphyloccocus aureus, Escherichia coli
      and Pseudomonas aeruginosa, either alone or in combination with Erythromycin
      (Ery), Gentamicin (Gen) and Ampicillin (Amp). Checkerboard assay demonstrated
      that Kumatakenin elicited synergistic effects with all three antibiotics, and
      chrysin displayed synergistic effect with Ery against L. monocytogenes. Further
      experiments showed that the synergy effect was sufficient to eradicate biofilms
      formed by L. monocytogenes. Thus, our data highlighted that the combinations of
      secondary metabolites from B. albiflora and specific antibiotics were useful for
      the treatment of pathogens, which might help prevent the spread of antibiotic
      resistance through improving antibiotic effectiveness.

PMID- 30298932
TI  - Inequalities in dental caries in children within the UK: Have there been changes
      over time?
AB  - OBJECTIVES: To examine any change over time in the association between
      deprivation and caries experience between 2003 and 2013 in a nationally
      representative sample of UK children. METHODS: Data from UK Children's Dental
      Health Surveys, 2003 and 2013, were used. The target population was 5-, 8-, 12-
      and 15-year-olds. A total of 9604 children in 2003 and 9866 in 2013 were included
      in the surveys. Outcome variables were any active caries, caries experience and
      total number of carious teeth. Family socio-economic position (SEP) or
      deprivation level was measured at school level using eligibility for free school
      meals (FSM) to identify children from low-income families. Incidence rate ratios
      (IRR) and pooled standardized incidence rates ratios were calculated to measure
      dichotomous outcome variables by year, age group and status of deprivation. The
      study continuous outcome was modelled using a zero-inflated Poisson regression
      while the dichotomous outcomes were modelled using logistic regressions. The
      multivariable analyses were run by age groups accounting for year, sex and
      deprivation status. RESULTS: The percentage of those identified as deprived was
      significantly higher in 2013 (35.8% in 2013 vs 26.0% in 2003, P < 0.001). Among
      both deprived and non-deprived children, the prevalence of any active caries
      significantly dropped over the years, observed in all age groups. Comparing 2013
      with 2003 and accounting for sex, deprivation level, "any active caries," "any
      caries experience" and "total number of carious teeth" significantly dropped were
      observed in all age groups. Comparing the years, the association of deprivation
      with caries outcomes mostly remained the same or decreased. This decrease was
      predominantly seen in "any caries experience." Only among the 5-year-olds, did
      the association between deprivation and total number of carious teeth over the
      years significantly increase. For all age groups, the likelihood of "any active
      caries" and "total number of carious teeth" by deprivation remained the same
      comparing the two points in time: 2003 and 2013. However, irrespective of year,
      deprivation was significantly associated with caries observed in all age groups.
      CONCLUSION: In the UK, the prevalence of active dental caries and caries
      experience has decreased in the period between 2003 and 2013. Similarly, the
      likelihood of having dental caries by deprivation in 2013 was predominantly lower
      than that observed in 2003.

PMID- 30298933
TI  - A path integral molecular dynamics study on intermolecular hydrogen bond of
      acetic acid-arsenic acid anion and acetic acid-phosphoric acid anion clusters.
AB  - We apply ab initio path integral molecular dynamics simulation employing
      omegaB97XD as the quantum chemical calculation method to acetic acid-arsenic acid
      anion and acetic acid-phosphoric acid anion clusters to investigate the
      difference of the hydrogen bond structure and its fluctuation such as proton
      transfer. We found that the nuclear quantum effect enhanced the fluctuation of
      the hydrogen bond structure and proton transfer, which shows treatment of the
      nuclear quantum effect was essential to investigate these systems. The hydrogen
      bond in acetic acid-arsenic acid anion cluster showed characters related to low
      barrier hydrogen bonds, while acetic acid-phosphoric acid anion cluster did not.
      We found non-negligible distinction between these two systems, which could not be
      found in conventional calculations. We suggest that the difference in amount of
      atomic charge of the atoms consisting the hydrogen bond is the origin of the
      difference between acetic acid-arsenic acid and acetic acid-phosphoric acid anion
      cluster. (c) 2018 Wiley Periodicals, Inc.

PMID- 30298934
TI  - A Niche Mechanism for beta-Cell Regeneration in Type 1 Diabetes.

PMID- 30298935
TI  - Dynamics fingerprints of active conformers of epidermal growth factor receptor
      kinase.
AB  - Epidermal growth factor receptor (EGFR) is a prototypical cell-surface receptor
      that plays a key role in the regulation of cellular signaling, proliferation and
      differentiation. Mutations of its kinase domain have been associated with the
      development of a variety of cancers and, therefore, it has been the target of
      drug design. Single amino acid substitutions (SASs) in this domain have been
      proven to alter the equilibrium of pre-existing conformer populations. Despite
      the advances in structural descriptions of its so-called active and inactive
      conformations, the associated dynamics aspects that characterize them have not
      been thoroughly studied yet. As the dynamic behaviors and molecular motions of
      proteins are important for a complete understanding of their structure-function
      relationships we present a novel procedure, using (or based on) normal mode
      analysis, to identify the collective dynamics shared among different conformers
      in EGFR kinase. The method allows the comparison of patterns of low-frequency
      vibrational modes defining representative directions of motions. Our procedure is
      able to emphasize the main similarities and differences between the collective
      dynamics of different conformers. In the case of EGFR kinase, two representative
      directions of motions have been found as dynamics fingerprints of the active
      conformers. Protein motion along both directions reveals to have a significant
      impact on the cavity volume of the main pocket of the active site. Otherwise, the
      inactive conformers exhibit a more heterogeneous distribution of collective
      motions. (c) 2018 Wiley Periodicals, Inc.

PMID- 30298936
TI  - Kettle test efficacy in predicting cognitive and functional outcomes in geriatric
      rehabilitation.
AB  - BACKGROUND/AIM: Limited research has been available to support the use of the
      Kettle Test in a subacute rehabilitation setting with patients diagnosed with a
      variety of medical conditions. The Kettle Test is an occupation based performance
      measure designed to detect cognitive processes and function. The aim of this
      research was to measure the correlation between three cognitive tests, the Mini
      Mental State Examination (MMSE), Cognitive Functional Independence Measure
      (Cognitive FIM) and the Kettle Test. Secondly, to assess the efficacy of these
      tests in predicting functional outcomes via the motor subscale of the Functional
      Independence Measure (mFIM). METHODS: A prospective single-centre cohort study in
      a subacute rehabilitation setting of 97 patients. RESULTS: Correlation
      coefficients between the tests were statistically significant and moderately
      strong, with values ranging from 0.593 to -0.589. Significant positive
      correlations were seen between admission MMSE, Cognitive FIM and the mFIM and
      significant negative correlations between Kettle Test scores and the mFIM. The
      Kettle Test score had a stronger relationship with mFIM (r = -0.40; P < 0.01)
      compared to the Cognitive FIM (r = 0.33; P < 0.01) and MMSE (r = 0.26; P < 0.05).
      The Kettle Test variance is significantly associated with the MMSE and Cognitive
      FIM at admission and discharge measures. Modelling identified that age and gender
      significantly contribute to this relationship. When adjusted for age and gender
      the MMSE and Cognitive FIM both explained the 47% of the variance at discharge.
      CONCLUSION: There were statistically significant inter-test correlations between
      the MMSE, Cognitive FIM and Kettle Test. The Kettle Test had the strongest
      relationship to patient functional outcomes.

PMID- 30298938
TI  - Corrigendum for Crovetto, Figueras, Triunfo, et al. (2014)
      https://doi.org/10.1002/pd.4519.

PMID- 30298937
TI  - Numerical Approach to Study the Behavior of an Artificial Ventricle: Fluid
      Structure Interaction Followed By Fluid Dynamics With Moving Boundaries.
AB  - Heart failure is a progressive and often fatal pathology among the main causes of
      death in the world. An implantable total artificial heart (TAH) is an alternative
      to heart transplantation. Blood damage quantification is imperative to assess the
      behavior of an artificial ventricle and is strictly related to the hemodynamics,
      which can be investigated through numerical simulations. The aim of this study is
      to develop a computational model that can accurately reproduce the hemodynamics
      inside the left pumping chamber of an existing TAH (Carmat-TAH) together with the
      displacement of the leaflets of the biological aortic and mitral valves and the
      displacement of the pericardium-made membrane. The proposed modeling workflow
      combines fluid-structure interaction (FSI) simulations based on a fixed grid
      method with computational fluid dynamics (CFD). In particular, the kinematics of
      the valves is accounted for by means of a dynamic mesh technique in the CFD. The
      comparison between FSI- and CFD-calculated velocity fields confirmed that the
      presence of the valves in the CFD model is essential for realistically mimicking
      blood dynamics, with a percentage difference of 2% during systole phase and 13%
      during the diastole. The percentage of blood volume in the CFD simulation with a
      shear stress above the threshold of 50 Pa is less than 0.001%. In conclusion, the
      application of this workflow to the Carmat-TAH provided consistent results with
      previous clinical studies demonstrating its utility in calculating local
      hemodynamic quantities in the presence of complex moving boundaries.

PMID- 30298939
TI  - Response to comment on "First Trimester screening for early and late preeclampsia
      based on maternal characteristics, biophysical parameters, and angiogenic
      factors".

PMID- 30298940
TI  - Comment on "First Trimester screening for early and late preeclampsia based on
      maternal characteristics, biophysical parameters, and angiogenic factors".

PMID- 30298941
TI  - BEHAVIORAL EFFECTS OF COPPER ON LARVAL WHITE STURGEON.
AB  - Early life stage white sturgeon are sensitive to copper with adverse behavioral
      responses observed during previous studies. The objectives of the present study
      were to quantify the effects of copper exposure on white sturgeon swimming and
      feeding behaviors and determine their time to response. Larval sturgeon (1-2, 28
      or 35 days post hatch) were exposed to copper (0.5-8 ug/L) for 4-14 days.
      Abnormal behavioral changes were observed within the first few days of exposure
      including loss of equilibrium and immobilization. Digital video tracking software
      revealed decreased swimming activity with increasing copper concentration.
      Significant changes in behavior and mortality occurred at concentrations of
      copper between 1-8 ug/L. Juvenile white sturgeon, 58 days post hatch, exposed to
      12 ug/L copper consumed 37-60% less food than controls after 3 days of exposure.
      Our results indicate that behavioral endpoints were more sensitive than some
      standard toxicity test endpoints and can be effectively expand the sensitivity of
      standard toxicity tests for white sturgeon. Swimming behavior was impaired to the
      extent that survival in the field would likely be jeopardized. Such data would
      provide managers a useful metric for characterizing the risks of copper
      contamination to white sturgeon. This article is protected by copyright. All
      rights reserved.

PMID- 30298942
TI  - Is it justifiable to pool Chironomus species in trace element contamination
      studies?
AB  - Larvae of the insect Chironomus (Chironomidae, Diptera) have great potential for
      estimating the bioavailability of sedimentary trace elements since they are
      common in fine sediments and tolerate high concentrations of these contaminants.
      Their use as biomonitors is limited by the fact that they are difficult to
      identify to species, and species can differ in their trace element
      concentrations. To determine if pooling species would compromise their use as
      trace element biomonitors, we identified species of Chironomus larvae collected
      from 22 lakes and measured their concentrations of 9 trace elements. We found
      that the concentrations of As, Ba, Co, Cu, Mn and Ni did not generally differ
      between sympatric Chironomus species, which indicates that they could be pooled
      for analyses of these trace elements. In contrast, we found that Cd, Se and Zn
      concentrations differed between species living at the same site according to
      their feeding behavior, that is, Chironomus species feeding on oxic sediments
      tended to have higher Cd and Zn concentrations, whereas those feeding on deeper
      anoxic sediments had higher Se concentrations. Since Se and Zn concentrations in
      sympatric Chironomus species usually differed by only a factor of two, separating
      species based on their feeding behavior might not be as crucial as for Cd if
      larval Se and Zn concentrations vary greatly from site to site. This article is
      protected by copyright. All rights reserved.

PMID- 30298943
TI  - AMS-800 Artificial urinary sphincter in female patients with stress urinary
      incontinence: A systematic review.
AB  - AIMS: To perform a systematic review of studies reporting the outcomes of AMS-800
      artificial urinary sphincter (AUS) implantation in female patients with stress
      urinary incontinence (SUI) resulting from intrinsic sphincter deficiency (ISD).
      METHODS: A systematic literature search of the Medline and Embase databases was
      performed in June 2018 in accordance with the PRISMA statement. No time limit was
      used. The protocol was registered in PROSPERO (CRD42018099612). Study selection
      and data extraction were performed by two independent reviewers. RESULTS: Of 886
      records screened, 17 were included. All were retrospective or prospective non
      comparative case series. One study reported on vaginal AUS implantation, 11 on
      open AUS implantation, two on laparoscopic AUS implantation, two on robot
      assisted AUS implantation and one compared open and robot-assisted implantations.
      The vast majority of patients had undergone at least one anti-incontinence
      surgical procedure prior to AUS implantation (69.1-100%). The intraoperative
      bladder neck injury rates ranged from 0% to 43.8% and the intraoperative vaginal
      injury rates ranged from 0 to 25%. After mean follow-up periods ranging from 5 to
      204 months, the complete continence rates ranged from 61.1% to 100%. The rates of
      explantation, erosion and mechanical failure varied from 0% to 45.3%, 0% to 22.2%
      and 0% to 44.1%, respectively. CONCLUSIONS: AMS-800 AUS can provide excellent
      functional outcomes in female patients with SUI resulting from ISD but at the
      cost of a relatively high morbidity. High level of evidence studies are needed to
      help better define the role of AUS in the female SUI armamentarium.

PMID- 30298945
TI  - Suicide Risk and Emotional Responses to Thoughts of Death: The Response to Morbid
      Ideations Questionnaire.
AB  - BACKGROUND: There is need for deeper understanding of the processes by which
      suicidal thoughts lead to action. Examination of morbid ideation and the
      emotional sequelae of such ideation that may feed suicide ideation (SI) and
      attempts (SA) have been limited. METHOD: Adult psychiatric outpatients (N = 385)
      were administered the Response to Morbid Ideation Questionnaire (RMI-Q) and
      measures of SI, suicidal thoughts and behaviors (STB), and other psychiatric
      symptom severity. We examined (1) incidence and prevalence in mentation of morbid
      ideations and emotional responses to these ideations, (2) differences in
      emotional responses between individuals of varying levels of suicide history, and
      (3) the relationships of different types of morbid ideations and emotional
      responses with concurrent SI and symptom severity. RESULTS: Morbid ideation was
      reported by 87.5% of participants and associated with lifetime and concurrent
      levels of SI/STB. Calm/relieved emotional responses were associated with lifetime
      and concurrent levels of SI/STB, while negative-valence responses to morbid
      ideations were associated with concurrent severity of psychopathology.
      CONCLUSIONS: Our results suggest that the role of morbid ideation and its
      emotional sequelae in the development of suicidal motivation and action deserves
      further attention and may be a treatment target for suicide risk reduction.

PMID- 30298944
TI  - Copper toxicity in Bristol Bay headwaters: Part 2-olfactory inhibition in low
      hardness water.
AB  - We investigated the olfactory toxicity of copper (Cu) to rainbow trout in low
      hardness (27 mg/L as CaCO3 ) water formulated in the laboratory over a 120-h
      period using a flow-through design. The fish's response to an alarm cue (e.g.,
      reduction in activity) was recorded to determine the exposure concentrations and
      durations that inhibited olfactory detection of the cue after 3, 24, 48, and 96 h
      of Cu exposure and after 24 h of clean water recovery following the 96-h exposure
      period. Exposures were conducted with a range of Cu concentrations from 0.13
      (control) to 7.14 MUg Cu/L (dissolved Cu). We observed a dose-dependent response
      in olfactory inhibition with a 20% reduction in the probability of responding to
      the alarm cue, relative to controls, at 2.7 and 2.4 MUg Cu/L after 24 or 96 h of
      exposure, respectively. Olfactory inhibition manifested between 3 and 24 h of
      exposure. Our 24- and 96-h 20% olfactory inhibition estimates fell between the
      criteria derived using the biotic ligand model (BLM; criterion maximum
      concentration [CMC] and criterion continuous concentration [CCC] values were 0.63
      and 0.39 MUg Cu/L, respectively) and water hardness-based criteria (CMC and CCC
      values were 3.9 and 2.9 MUg Cu/L, respectively). Therefore, the hardness-based
      criteria do not appear to be protective and the BLM-derived criteria do appear to
      be protective against Cu-induced olfactory inhibition given our test water
      chemistry. Neither the hardness-based criteria nor the BLM-derived criteria
      appear to be protective against our estimated Cu behavioral avoidance response
      concentrations at 24- and 96-h exposures (0.54 and 0.50 MUg Cu/L, respectively).
      Environ Toxicol Chem 2018;9999:1-12. (c) 2018 SETAC.

PMID- 30298947
TI  - Suicide Exposure in Law Enforcement Officers.
AB  - OBJECTIVE: To examine occupational and personal suicide exposure among Law
      Enforcement Officers (LEOs) and related mental health outcomes. METHODS: Law
      Enforcement Officers (N = 813) completed an online survey about their suicide
      exposure, whether scenes stayed with them, and current symptoms of depression,
      anxiety, PTSD, and suicidal ideation. RESULTS: Almost all participants (95%) had
      responded to at least one suicide scene with an average of 30.90 (SD = 57.28)
      career suicide scenes and 2.17 in the last year (SD = 4.11). One in five (22%)
      reported a scene that they cannot shake or have nightmares about, and 42.5%
      reported one scene that stayed with them. Almost three fourths (73.4%) knew
      someone personally who had died by suicide. There was a significant association
      between high levels of occupational exposure to suicide and behavioral health
      consequences including PTSD, persistent thoughts of a suicide scene, and the
      inability to shake a scene. The inability to shake a scene and having a scene
      stick with them was associated with increased symptoms of depression, anxiety,
      PTSD, and suicidal ideation. CONCLUSIONS: LEOs experience a tremendous amount of
      exposure to suicide scenes and also have personal exposure. There is a need for
      training to mitigate the effect of these multiple traumas on their mental health.

PMID- 30298946
TI  - Genotype imputation accuracy in multiple equine breeds from medium- to high
      density genotypes.
AB  - Genotype imputation is now a key component of genomic analyses as it increases
      the density of available genotypes within a population. However, many factors can
      influence imputation accuracy. The aim of this study was to assess and compare
      the accuracy of imputation of high-density genotypes (Affymetrix Axiom Equine
      genotyping array, 670,806 SNPs) from two moderate-density genotypes (Illumina
      Equine SNP50 BeadChip, 54,602 SNPs and Illumina Equine SNP70 BeadChip, 65,157
      SNPs), using single-breed or multiple-breed reference sets. Genotypes were
      available from five groups of horse breeds: Arab (AR, 1,207 horses), Trotteur
      Francais (TF, 979 horses), Selle Francais (SF, 1,979 horses), Anglo-Arab (AA, 229
      horses) and various foreign sport horses (FH, 209 horses). The proportions of
      horses genotyped with the high-density (HD) chip in each breed group were 10% in
      AA, 15% in AR and FH, 30% in TF and 57% in SF. A validation set consisting of one
      third of the horses genotyped with the HD chip was formed and their genotypes
      deleted. Two imputation strategies were compared, one in which the reference
      population consisted only of horses from the same breed group as in the
      validation set, and another with horses from all breed groups. For the first
      strategy, concordance rates (CRs) ranged from 97.8% (AR) to 99.0% (TF) and
      correlations (r2) from 0.94 (AR) to 0.99 (TF). For the second strategy, CR ranged
      from 97.4% (AR) to 98.9% (TF) and r2 from 0.93 (AR) to 0.99 (TF). Overall, the
      results show a small advantage of within-breed imputation compared with multi
      breed imputation. Adding horses from different breed groups to the reference
      population does not improve the accuracy of imputation. Imputation provides an
      accurate means of combining data sets from different genotyping platforms, now
      necessary with the increasing use of the recently developed Affymetrix Axiom
      Equine genotyping array.

PMID- 30298948
TI  - Characterization of DNA double-strand break repair pathways in diffuse large B
      cell lymphoma.
AB  - Efficient DNA repair is indispensable for maintaining genomic integrity in
      humans. Cancer associated deletions and mutations are mainly due to misrepaired
      DNA double-strand breaks (DSBs). Classical nonhomologous end joining (c-NHEJ) and
      homologous recombination (HR) are two major DSB repair pathways in humans. An
      error prone, alternative NHEJ pathway that utilizes microhomology was also
      reported in cancer cells and to a lesser extent in normal cells. In the present
      study, we evaluated the efficiency of various DSB repair pathways in the most
      common lymphoma, the diffuse large B cell lymphoma (DLBCL). Here we show that DNA
      repair through c-NHEJ pathway is limited in SUDHL8, a cell line derived from a
      DLBCL patient. Unlike c-NHEJ, microhomology mediated end joining (MMEJ) was
      predominant at physiological temperature. Consistent with the observation,
      expression level of repair proteins such as LIGASE I, LIGASE III, PARP1, CtIP,
      and MRE11 was higher in DLBCL cells when compared to c-NHEJ proteins. Further,
      inhibition of LIGASE I or MRE11, led to reduction in the efficiency of MMEJ in
      DLBCL cells. Besides, HR-mediated DSB repair occurring through gene conversion
      was observed. Thus, our results reveal the predominance of MMEJ over c-NHEJ in
      repairing DSBs in DLBCL cells, while error-free repair through HR was also
      evident.

PMID- 30298949
TI  - Fluctuating operation development index of community health service centres in
      the Pudong new area of Shanghai: A continuous investigation.
AB  - BACKGROUND: Previous performance evaluations among community health service
      centres (CHSCs) have been mainly based on absolute indicators, while the
      operation index, a more comprehensive evaluation method, has been rarely used in
      evaluation. This study aimed to develop a set of operation index suitable for the
      evaluation of CHSCs in Pudong. METHODS: The operation index system, developed
      based on a literature review, focus group, and factor analysis, was applied to
      all 45 CHSCs in Pudong. The data were mainly derived from the Pudong Health
      Statistics Information System from 2010 to 2014. The analysis included a
      descriptive analysis, t tests, variance analysis, and repeated measures analysis
      of variance. RESULTS: Different aspects of the operation index showed different
      developing trends during 2010 to 2014. The overall operation, service operation,
      management condition, and comprehensive satisfaction index were significantly
      different in different years (P < 0.05). However, the differences in the
      development foundation index were not obvious (P > 0.05). Moreover, the regional
      factor and medical association influenced the performance of service operation
      index, and the informatization level affected the performance of overall
      operation and management condition index (P < 0.05), with different family GP
      programmes level affecting management condition index (P < 0.05). CONCLUSION:
      Changes in the management condition index led to fluctuations in overall
      operation in the CHSCs. Since regional factors, family GP programmes, and medical
      associations promoted the operation of CHSCs, we advocate a multi-dimensional
      evaluation combining horizontal performance appraisal and vertical index
      evaluation to focus on these factors.

PMID- 30298950
TI  - MR study of longitudinal variations in proximal femur 3D morphological shape and
      associations with cartilage health in hip osteoarthritis.
AB  - The goal of this study was to use quantitative MRI analysis to longitudinally
      observe the relationship between 3D proximal femur shape and hip joint
      degenerative changes. Forty-six subjects underwent unilateral hip MR imaging at
      three time points (baseline, 18 and 36 months). 3D shape analysis, hip cartilage
      T1rho /T2 relaxation time quantification, and SHOMRI MRI grading were performed
      at each time point. Subjects were grouped based on KL, SHOMRI, and HOOS pain
      scores. Associations between these score groupings, time, and longitudinal
      variation in shape, were analyzed using a generalized estimating equation. One
      way ANCOVA was conducted to evaluate change in shape as a predictor of the
      worsening of degenerative changes at 36 months. Our results demonstrated that
      subjects displayed an increase in the volume of the femoral head and neck (Mode
      3) over time. This shape mode was significantly more prevalent in patients that
      reported pain. Longitudinal changes in this shape mode also served as borderline
      predictors of elevated T1rho values (p = 0.055) and of cartilage lesions (p =
      0.068). Subjects showed a change in the Femoral Neck Anteversion angle (FNA) over
      time (Mode 6). This shape mode showed a significant interaction with the presence
      of cartilage lesions. The results of this study suggest that specific variations
      in bone shape quantified through 3D-MRI based Statistical Shape modeling show an
      observable relationship with hip joint compositional and morphological changes.
      The shapes observed lead to early degenerative changes, which may lead into OA,
      thus confirming the important role of bone shape changes in the pathogenesis of
      OA. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J
      Orthop Res.

PMID- 30298951
TI  - Pyrazinoates as antiparasitic agents against Trypanosoma cruzi.
AB  - This work reports a repurposing study of pyrazinoic acid (1) and methyl (2),
      ethyl (3) and 2-chloroethyl (4) ester derivatives with antimycobacterial
      activity, in assays against Trypanosoma cruzi. The compounds and benznidazole,
      the standard antitrypanosoma drug, were evaluated in concentrations ranging from
      100 to 6.25 MUg/mL. The results showed that compounds 2 and 3 (EC50  = 182 and
      447 MUM) significantly reduced the infection rate of the parasite into the
      mammalian cells at 100 MUg/mL (p < 0.05) in a similar way to benznidazole. In
      addition, all the compounds also significantly reduced the number of
      intracellular parasites (compound 1 at 50 MUg/mL, and compounds 2-4 at 100
      MUg/mL, p < 0.05) in comparison to the control. Compounds 1 and 2 were more
      effective than benznidazole at 50 MUg/mL (p < 0.001). Moreover, compounds 1-4 did
      not show significant cytotoxicity against THP-1, J774, and HeLa cells (>1000
      MUM), indicating that they possess considerable selectivity against the
      parasites. This report represents the first study of such compounds against T.
      cruzi, indicating the potential of pyrazinoates as antiparasitic agents.

PMID- 30298953
TI  - Assessing the effectiveness of advanced nurse practitioners undertaking home
      visits in an out of hours urgent primary care service in England.
AB  - AIM: To measure the effectiveness of advanced nurse practitioners (ANPs) against
      national quality requirements for out-of-hours (OOH) care, to compare ANP
      effectiveness with that of doctors working in the same service, and to evaluate
      the impact of ANPs on the service. BACKGROUND: There is little documented
      evidence of ANPs undertaking urgent home visits in the OOH setting. This study
      advances current knowledge of this aspect of the OOH service and makes
      recommendations for the management of the ANP urgent home visiting service.
      METHODS: Analysis of 1,539 ANP home-visit patient electronic case notes over a 12
      month period, a focus group of eight GPs, and interviews with six ANPs. RESULTS:
      Advanced nurse practitioners are as effective as GPs in undertaking urgent home
      visits. Their documentation is more consistent and their refer-on rate to
      secondary care is less than that of GP colleagues. CONCLUSION: Advanced nurse
      practitioners can provide equivalent clinical outcomes to GPs when undertaking
      urgent home visits. IMPLICATIONS FOR NURSING MANAGEMENT: This study adds to the
      body of evidence for the positive impact of ANPs on OOH service delivery and
      managers can be assured that they are practising at a level that makes them
      effective and safe to undertake this role.

PMID- 30298952
TI  - IL-6 mediates ER expansion during hyperpolarization of alternatively activated
      macrophages.
AB  - Although recent evidence has shown that IL-6 is involved in enhanced alternative
      activation of macrophages toward a profibrotic phenotype, the mechanisms leading
      to their increased secretory capacity are not fully understood. Here, we
      investigated the effect of IL-6 on endoplasmic reticulum (ER) expansion and
      alternative activation of macrophages in vitro. An essential mediator in this ER
      expansion process is the IRE1 pathway, which possesses a kinase and
      endoribonuclease domain to cleave XBP1 into a spliced bioactive molecule. To
      investigate the IRE1-XBP1 expansion pathway, IL-4/IL-13 and IL-4/IL-13/IL-6
      mediated alternative programming of murine bone marrow-derived and human THP1
      macrophages were assessed by arginase activity in cell lysates, CD206 and
      arginase-1 expression by flow cytometry, and secreted CCL18 by ELISA,
      respectively. Ultrastructural intracellular morphology and ER biogenesis were
      examined by transmission electron microscopy and immunofluorescence.
      Transcription profiling of 128 genes were assessed by NanoString and
      Pharmacological inhibition of the IRE1-XBP1 arm was achieved using STF-083010 and
      was verified by RT-PCR. The addition of IL-6 to the conventional alternative
      programming cocktail IL-4/IL-13 resulted in increased ER and mitochondrial
      expansion, profibrotic profiles and unfolded protein response-mediated induction
      of molecular chaperones. IRE1-XBP1 inhibition substantially reduced the IL-6
      mediated hyperpolarization and normalized the above effects. In conclusion, the
      addition of IL-6 enhances ER expansion and the profibrotic capacity of IL-4/IL-13
      mediated activation of macrophages. Therapeutic strategies targeting IL-6 or the
      IRE1-XBP1 axis may be beneficial to prevent the profibrotic capacity of
      macrophages.

PMID- 30298954
TI  - Analysis of peripheral central venous access ports at the forearm: An
      observational study.
AB  - The aim of this study was to analyse the characteristics of central venous
      catheters with brachial-implanted reservoirs and the complications associated
      with their use over a 4-years period. This observational study was carried out in
      an onco-haematological day hospital in Spain. Information was collected about 125
      catheters inserted in patients requiring intravenous chemotherapy. There were
      more catheters implanted in women than men and the mean age was 58.6 years.
      Seventy of the implanted catheters were made of polyurethane and 55 of silicone.
      Left laterality prevailed with a mean catheter dwell-time of 347.1 days. A total
      of 164 complications were registered, 124 of them came from blood draws, where
      the most frequent complication was "inability to withdraw, ability to infuse".
      Forty complications were associated with the administration of treatments.
      Furthermore, there were 21 catheter removals, caused by several other
      complications different from those mentioned before. Statistically significant
      differences were found when associating types of catheters, laterality, blood
      draws and administration of treatments. Results showed how silicone ports would
      be more appropriate for patients who carry these types or ports than polyurethane
      because they reduce the number of complications causes by thrombosis.

PMID- 30298955
TI  - CardioVAI: An automatic implementation of ACMG-AMP variant interpretation
      guidelines in the diagnosis of cardiovascular diseases.
AB  - Variant interpretation for the diagnosis of genetic diseases is a complex
      process. The American College of Medical Genetics and Genomics, with the
      Association for Molecular Pathology, have proposed a set of evidence-based
      guidelines to support variant pathogenicity assessment and reporting in Mendelian
      diseases. Cardiovascular disorders are a field of application of these
      guidelines, but practical implementation is challenging due to the genetic
      disease heterogeneity and the complexity of information sources that need to be
      integrated. Decision support systems able to automate variant interpretation in
      the light of specific disease domains are demanded. We implemented CardioVAI
      (Cardio Variant Interpreter), an automated system for guidelines based variant
      classification in cardiovascular-related genes. Different omics-resources were
      integrated to assess pathogenicity of every genomic variant in 72 cardiovascular
      diseases related genes. We validated our method on benchmark datasets of high
      confident assessed variants, reaching pathogenicity and benignity concordance up
      to 83 and 97.08%, respectively. We compared CardioVAI to similar methods and
      analyzed the main differences in terms of guidelines implementation. We finally
      made available CardioVAI as a web resource (http://cardiovai.engenome.com/) that
      allows users to further specialize guidelines recommendations.

PMID- 30298956
TI  - Survey of procedural and resuscitation requirements for paediatricians working in
      a non-tertiary centre: Implications for training.
AB  - AIM: There are minimal data to guide the continuing medical education (CME) of
      general paediatricians working in non-tertiary hospitals. The aim of this study
      was to determine the procedural and resuscitation skills required by non-tertiary
      paediatricians and the frequency with which these skills are utilised. METHODS:
      Over a 12-month period (December 2012 to December 2013), each of the 11
      paediatricians involved in acute inpatient care at University Hospital Geelong
      (UHG) completed a weekly online survey regarding their inpatient clinical
      experience. This included procedures performed or directly supervised as well as
      their resuscitation involvement. RESULTS: Each of the 11 paediatricians who
      managed inpatients on a regular or semi-regular basis during the study period
      agreed to participate, and each completed all of the weekly surveys. There were
      seven UHG paediatricians with an inpatient appointment (each with a 0.27 full
      time equivalent (FTE) paediatrician workload) and four paediatricians providing
      inpatient cover on a locum basis. Over the course of 12 months, each 0.27 FTE
      paediatrician was, on average, involved in 11.3 neonatal, 1.7 infant and 2.4
      child resuscitations and performed 0.9 intubations. CONCLUSIONS: Paediatricians
      working at non-tertiary hospitals are required to perform and supervise critical
      procedural and resuscitation skills but have limited opportunities to maintain
      proficiency in such skills. General paediatric training and consultant
      paediatrician CME programmes should ensure the acquisition and maintenance of the
      procedural and resuscitation skills required for the management of seriously ill
      children in non-tertiary acute care settings.

PMID- 30298957
TI  - Ventilatory constraints influence physiological dead space in heart failure.
AB  - NEW FINDINGS: What is the central question of this study? The goal of this study
      was to investigate the effect of alterations in tidal volume and alveolar volume
      on the elevated physiological dead space and the contribution of ventilatory
      constraints thereof in heart failure patients during submaximal exercise. What is
      the main finding and its importance? We found that physiological dead space was
      elevated in heart failure via reduced tidal volume and alveolar volume.
      Furthermore, the degree of ventilatory constraints was associated with
      physiological dead space and alveolar volume. ABSTRACT: Patients who have heart
      failure with reduced ejection fraction (HFrEF) exhibit impaired ventilatory
      efficiency [i.e. greater ventilatory equivalent for carbon dioxide ( 

PMID- 30298959
TI  - The association between school holidays and unintentional fatal drowning among
      children and adolescents aged 5-17 years.
AB  - AIM: Children aged 5-17 years in Australia have one of the lowest unintentional
      fatal drowning rates. One possible explanation is the protective effect of formal
      schooling, reducing leisure time for exposure to water hazards. We examine
      differences in frequency and circumstances of drowning deaths in this age group
      between school holidays and school days in Australia. METHODS: A total population
      survey (2005-2014) of unintentional fatal drownings was extracted from the
      (Australian) Royal Life Saving National Fatal Drowning Database. Date of drowning
      incident and state of residence were used to determine if the drowning occurred
      during school days or school holidays (including public holidays). RESULTS: A
      total of 188 5-17 year-olds drowned during the study period. We found a
      statistically significant difference between drowning incidence during school
      holidays and school days, with relative risk (RR) of drowning on a holiday 2.40
      times higher (confidence interval (CI): 1.82-3.18) than on a school day. This
      risk was similar for males (RR = 2.41; CI: 1.75-3.33) and females (RR = 2.38; CI:
      1.33-4.27) but differs between children 5-9 years (RR = 3.05; CI: 1.98-4.72) and
      adolescents 10-17 years of age (RR = 2.02; CI: 1.38-2.93). CONCLUSIONS: Drowning
      rates among 5-17 year-olds are more than twice as high during holidays than on
      school days. Impact of school holidays was the strongest among younger children,
      visitors to the drowning location and in pools and inland waterways. Results were
      robust to alternative specifications excluding weekends and treating them as
      holidays. Prevention strategies may include counselling parents and care
      providers of the increased risk ahead of school holidays, education on drowning
      risk in the school curriculum and extra holidays for parents and care givers.

PMID- 30298958
TI  - Exploring children's experiences in community gambling venues: A qualitative
      study with children aged 6-16 in regional New South Wales.
AB  - ISSUE ADDRESSED: Community-based gambling venues provide a range of activities
      for children alongside adult products, such as gambling. However, there has been
      little examination of children's experiences with, and exposure to, a range of
      gambling and non-gambling activities within venues. METHODS: Visual sociology
      methods were used to measure unprompted recall, prompted recall, current use and
      intended adult use of activities in community gambling venues in 44 children who
      attended venues. Qualitative data were also collected to gain further insight
      into children's perceptions of the venue and the activities within. RESULTS:
      Children displayed high unprompted and prompted recall of gambling and
      nongambling activities within the venue. Children indicated positive perceptions
      of the venue overall. Just over half of the children (52.3%) reported current use
      of gambling activities in the venue. The large majority of the children indicated
      that they would attend community gambling venues as an adult (90.9%). CONCLUSION:
      This research provides a starting point in understanding the extent to which
      children are exposed to gambling products in community gambling venues. SO WHAT?:
      This research will be important for researchers, policy makers and practitioners
      in developing health promotion initiatives to prevent children from being exposed
      to gambling products in community settings.

PMID- 30298960
TI  - Healthcare professionals' perspectives on the prevalence, barriers and management
      of psychosocial issues in cancer care: A mixed methods study.
AB  - This cross-sectional mixed methods survey explores healthcare professionals'
      perspective on their management of cancer patients' psychosocial concerns, and
      barriers to integrate the psychosocial approach in their work. An invitation for
      participation was sent to 4,965 inpatient and outpatient working professionals,
      of which 583 responded (12% response rate), and 368 fully completed the survey.
      The majority of respondents does not use a systematic approach to discuss
      patients' psychosocial concerns, 37.5% use the general question "How are you?,"
      and 65.0% spontaneously addresses various psychosocial aspects. Most psychosocial
      topics are "sometimes" or "regularly" discussed. Sexuality and return to work are
      rarely mentioned. About half of the respondents are convinced that they pay
      enough attention to the psychosocial well-being of cancer patients: by listening,
      engaging in a deeper conversation, providing advice and through referral. Mostly,
      patients are referred to a psychologist, a general practitioner, a social worker,
      a specialised nurse or a centre for well-being and mental health. The barriers
      experienced, when providing psychosocial support, can be attributed to the
      patients, to themselves or other healthcare professionals, and to policy
      restrictions. These barriers should be addressed in order to enable healthcare
      professionals to improve the integration of the psychosocial approach in cancer
      care.

PMID- 30298962
TI  - Knowledge, attitudes and practice of surgeons regarding nutritional support in
      CRS and HIPEC patients: Are we missing something?
AB  - Nutrition's impact on the surgical outcome has been established in various
      surgical specialties. However, data addressing the nutritional aspect following
      surgery for peritoneal surface malignancies are considered scarce. We aim to
      evaluate the knowledge, attitudes, and practice of surgeons regarding their
      nutritional support for patients undergoing cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) via a survey directed
      to self-evaluate nutritional knowledge, screening, and practice toward patients.
      The survey was submitted to the attendees of the International Regional Cancer
      Therapies Symposium. The response rate was 37% (56/151). Most surgeons estimated
      their knowledge and malnutrition screening skills in CRS and HIPEC to be
      'adequate' or better. Only 35.19% reported the availability of nutritional
      screening and assessment tools for CRS and HIPEC patients. 86.5% of participants
      stated that their CRS and HIPEC patients have access to a dietitian on inpatient
      and outpatient basis. However, only 32.69% reported to 'always' consult a
      dietitian. Otherwise, the involvement of a nutrition specialist is considered on
      variable basis. Despite the consensus on the importance of nutrition in HIPEC
      patients, there appears to be a profound underutilization of nutrition
      specialists in the patients' management, which may have had in impact on their
      surgical outcome.

PMID- 30298961
TI  - Evidence of increased fecal granins in children with irritable bowel syndrome and
      correlates with symptoms.
AB  - BACKGROUND: Granins have been implicated in the pathophysiology of irritable
      bowel syndrome (IBS) in adults. We sought to determine whether fecal granins are
      altered in children with IBS and associated with symptoms. METHODS: Children (7
      12 years of age) with IBS and healthy controls (HC) kept daily pain and stool
      diaries for 2 weeks. Stool samples were analyzed for chromogranins A and B (CgA,
      CgB) and secretogranins II and III (SgII, SgIII). Children also completed
      psychological measures to assess anxiety, depression, somatization, and
      internalizing symptoms. KEY RESULTS: Fecal CgB and SgIII concentrations were
      higher in all the boys (IBS plus HC, n = 48) than in all the girls (IBS plus HC,
      n = 75) (P = 0.02 and P = 0.046, respectively). CgA and SgIII were greater in
      children with IBS (n = 52) vs HC (n = 69) (P = 0.01, P = 0.017, respectively).
      CgB and SgII did not differ between groups. In children with IBS, the number of
      pain episodes per week and mean daily pain rating correlated positively with all
      four granins. The number of stools per day correlated positively with CgB and
      SgII, and the percent of diarrheal stools (6 or 7 on the Bristol Scale)
      correlated inversely with all four granins in boys but not in girls. Fecal
      granins did not correlate with psychological measures. CONCLUSIONS AND
      INFERENCES: As measured by fecal granins, there is evidence of neuroimmune
      activation in children with IBS. Granins are related to abdominal pain symptoms,
      stooling frequency, and stool form in children with IBS. Sex influences the fecal
      concentration of CgB and SgIII.

PMID- 30298963
TI  - Epidermal growth factor receptor promotes glioma progression by regulating xCT
      and GluN2B-containing N-methyl-d-aspartate-sensitive glutamate receptor
      signaling.
AB  - Autocrine and paracrine factors, including glutamate and epidermal growth factor
      (EGF), are potent inducers of brain tumor cell invasion, a pathological hallmark
      of malignant gliomas. System xc(-) consists of xCT and CD98hc subunits and
      functions as a plasma membrane antiporter for the uptake of extracellular cystine
      in exchange for intracellular glutamate. We previously showed that the EGF
      receptor (EGFR) interacts with xCT and thereby promotes the activity of system
      xc(-) in a kinase-independent manner, resulting in enhanced glutamate release in
      glioma cells. However, the molecular mechanism underlying EGFR-mediated glioma
      progression in a glutamate-rich microenvironment has remained unclear. Here we
      show that the GluN2B subunit of the N-methyl-d-aspartate-sensitive glutamate
      receptor (NMDAR) is a substrate of EGFR in glioma cells. In response to EGF
      stimulation, EGFR phosphorylated the COOH-terminal domain of GluN2B and thereby
      enhanced glutamate-NMDAR signaling and consequent cell migration in EGFR
      overexpressing glioma cells. Treatment with the NMDAR inhibitor MK-801 or the
      system xc(-) inhibitor sulfasalazine suppressed EGF-elicited glioma cell
      migration. The administration of sulfasalazine and MK-801 also synergistically
      suppressed the growth of subcutaneous tumors formed by EGFR-overexpressing glioma
      cells. Furthermore, shRNA-mediated knockdown of xCT and GluN2B cooperatively
      prolonged the survival of mice injected intracerebrally with such glioma cells.
      Our findings thus establish a central role for EGFR in the signaling crosstalk
      between xCT and GluN2B-containing NMDAR in glioma cells.

PMID- 30298964
TI  - Transcutaneous electrical acustimulation synchronized with inspiration improves
      gastric accommodation impaired by cold stress in healthy subjects.
AB  - BACKGROUND: The aim of this study was to investigate whether transcutaneous
      electrical acustimulation (TEA) synchronized with inspiration (STEA), a method
      known to enhance vagal activity, was more effective than TEA in improving cold
      stress-induced impairment in gastric accommodation (GA) and dyspeptic symptoms in
      healthy subjects. METHODS: Each of fifteen healthy subjects was studied in five
      randomized sessions: control (warm nutrient liquid), cold nutrient liquid (CNL),
      CNL+sham-TEA, CNL+TEA, and CNL+STEA. The subjects were requested to drink Ensure
      until reaching maximum satiety. STEA was performed using the same parameters as
      TEA but asking the subjects to breathe in when they sensed each stimulation
      train. The electrogastrogram (EGG) and electrocardiogram (ECG) were recorded to
      assess gastric slow waves (GSW) and autonomic functions, respectively. KEY
      RESULTS: GA was reduced with the CNL in comparison with the warm drink but
      increased with TEA and STEA; STEA was more potent than TEA in improving GA; STEA
      was more potent in improving GSW than TEA; STEA significantly increased vagal
      activity and decreased sympathetic activity compared with TEA. CONCLUSIONS AND
      INFERENCES: TEA synchronized with inspiration is more potent than TEA in
      improving cold stress-induced impairment in GA and GSW and dyspeptic symptoms and
      might be a novel noninvasive therapy for treating stress-induced dysmotility and
      dyspeptic symptoms.

PMID- 30298965
TI  - Brain corticotropin-releasing factor signaling: Involvement in acute stress
      induced visceral analgesia in male rats.
AB  - BACKGROUND: Water avoidance stress (WAS) induces a naloxone-independent visceral
      analgesia in male rats under non-invasive conditions of monitoring. The objective
      of the study was to examine the role of brain CRF signaling in acute stress
      induced visceral analgesia (SIVA). METHODS: Adult male Sprague-Dawley rats were
      chronically implanted with an intracerebroventricular (ICV) cannula. The
      visceromotor response (VMR) to graded phasic colorectal distension (CRD: 10, 20,
      40, 60 mm Hg, 20 seconds, 4 minutes intervals) was monitored using manometry. The
      VMR to a first CRD (baseline) was recorded 5 minutes after an ICV saline
      injection, followed 1 hour later by ICV injection of either CRF (30, 100, or 300
      ng and 1, 3, or 5 MUg/rat) or saline and a second CRD, 5 minutes later. Receptor
      antagonists against CRF1 /CRF2 (astressin-B, 30 MUg/rat), CRF2 (astressin2 -B, 10
      MUg/rat), oxytocin (tocinoic acid, 20 MUg/rat), or vehicle were injected ICV 5
      minutes before CRF (300 ng/rat, ICV) or 15 minutes before WAS (1 hour). KEY
      RESULTS: ICV CRF (100 and 300 ng) reduced the VMR to CRD at 60 mm Hg by -36.6% +/
      6.8% and -48.7% +/- 11.7%, respectively, vs baseline (P < 0.001), while other
      doses had no effect and IP CRF (10 ug/kg) induced visceral hyperalgesia.
      Astressin-B and tocinoic acid injected ICV induced hyperalgesia and prevented the
      analgesic effect of ICV CRF (300 ng/rat) and WAS, while astressin2 -B only
      blocked WAS-induced SIVA. CONCLUSIONS & INFERENCES: These data support a role for
      brain CRF signaling via CRF2 in SIVA in a model of WAS and CRD likely mediated by
      the activation of brain oxytocin pathway.

PMID- 30298966
TI  - Granulosa cells of prepubertal cattle respond to gonadotropin signaling and
      upregulate genes that promote follicular growth and prevent cell apoptosis.
AB  - Oocytes collected from prepubertal animals are known to be less developmentally
      competent than those from adult animals. There is evidence suggesting that
      acquisition of developmental competence in bovine oocytes may be linked to the
      expression profile of genes in the granulosa cells (GCs). Cumulus-oocyte
      complexes (COC) and GCs were collected from 12 Holstein heifers between 2 and 6
      months of age (nine follicle-stimulating hormone [FSH] treated and three
      untreated) and eight FSH-treated cows. The COCs from prepubertal animals were
      matured, fertilized, and cultured in vitro to assess development to the
      blastocyst stage. The relative messenger RNA (mRNA) abundance of FSHR, StAR,
      CYP19A1, HSD3B1, CX43, FOXO1, and XIAP in GCs were quantified by real-time
      quantitative polymerase chain reaction. Results from this study revealed that GCs
      of prepubertal animals respond to FSH treatment by increasing mRNA levels of
      genes promoting estradiol synthesis and follicular growth ( FSHR and CYP19A1),
      and preventing cell apoptosis ( XIAP), and by decreasing mRNA levels of genes
      promoting progesterone production ( StAR and HSD3B1). This study also revealed
      that the relative mRNA abundance of FOXO1 in GCs is associated with oocyte
      competence to support embryo development to the blastocyst stage in prepubertal
      Holstein heifers.

PMID- 30298967
TI  - Actions helping expressed or anticipated needs: Patients with advanced cancer and
      their family caregivers' experiences of specialist palliative home care teams.
AB  - Patients with advanced cancer and family caregivers in palliative care face
      physical, psychological, social and existential challenges, much of the time home
      alone. Specialist palliative home care team services can be instrumental for
      sense of security in an uncertain situation. The aim of this study was to
      describe patients' and family caregivers' experiences of specialist palliative
      home care team actions that are identified by the participants as helping or
      hindering interventions. Six patients and seven family caregivers were
      interviewed using the enhanced critical incident technique. Ninety-five critical
      incidents and wish list items were identified. Providing adequate resources,
      keeping promises and being reliable, and creating partnerships are actions by
      specialist palliative care teams that patients and family caregivers experienced
      as helping in meeting expressed or anticipated needs in patients and family
      caregivers. Being reliable and including patients and family caregivers in
      partnerships help to continue with daily life, even though death may be close.
      Unmet needs resulted in experiences of disrespect or violation of personal
      space/integrity.

PMID- 30298968
TI  - Exercise training in heart failure: a long way to go yet.

PMID- 30298969
TI  - Diathermy excisional haemorrhoidectomy - still the gold standard - a video
      vignette.

PMID- 30298970
TI  - A retrospective study of the impact of supraglottic airway devices on the
      appearance of neck masses in children undergoing serial magnetic resonance
      imaging.
AB  - BACKGROUND: General anesthesia and sedation are used routinely for magnetic
      resonance imaging (MRI) studies in children to optimize image quality. Airway
      devices such as supraglottic airways (SGAs) can alter the appearance of cervical
      soft tissue regions on an MRI and increase the risk of misdiagnosis. This
      phenomenon has not been well described in vivo. AIMS: We conducted this
      retrospective study to determine how often SGAs affected the appearance of neck
      masses in children who received multiple anesthetics for MRIs with and without an
      SGA. METHODS: We retrieved data on children 17 years old and younger who had
      multiple MRIs between January 2005 and January 2015. Inclusion criteria were
      patients with neck masses who had a SGA for at least one MRI and either a natural
      airway or endotracheal tube (ETT) for another MRI. We reviewed MRI images and
      imaging reports to determine if SGAs affected the appearance of neck masses.
      RESULTS: Twelve of the 921 patients who received anesthesia for neck MRIs during
      the study period met the inclusion criteria. SGAs affected the appearance of the
      neck mass in 11 of the 12 patients. CONCLUSIONS: Supraglottic airways can
      significantly alter the appearance of neck masses in children undergoing MRIs and
      affect radiologists' ability to assess those masses. Communication with the
      radiologist prior to the induction of anesthesia is crucial when using
      supraglottic devices in this patient population. It may be more prudent to use a
      different airway device and/or anesthetic technique when MRIs of these neck
      masses are undertaken.

PMID- 30298971
TI  - Greater insulin response to acute fructose ingestion among Maori and Pacific
      people compared to European people living in Aotearoa New Zealand.
AB  - BACKGROUND/OBJECTIVES: Fructose consumption has been linked with insulin
      resistance, obesity, and diabetes, which are more prevalent in those of Maori or
      Pacific ethnicity compared to New Zealand European. The aim of this study was to
      determine whether the acute effects of fructose consumption on serum glucose,
      insulin, lipids and C-reactive protein, differs according to body mass index
      (BMI) and/or ethnicity. SUBJECTS/METHODS: Maori (n=25), Pacific (n=26) or New
      Zealand European (n=25) ethnicity, participants consumed a 64g fructose/16g
      glucose solution. Changes in lipids, glucose, insulin, and C-reactive protein
      were analyzed using mixed models for repeated measures. RESULTS: After adjustment
      for age and sex, those with higher BMI had a higher glucose (p=0.0064) and
      insulin (p=0.0007) response than those with lower BMI. Those of Maori or Pacific
      ethnicity had similar glucose (p=0.077) to New Zealand European, but higher
      insulin responses (p=0.0005), which remained after additional adjustment for BMI
      (p=0.001). Reported sugar sweetened beverages (SSB) intake was higher among Maori
      and Pacific than New Zealand European (median 1.0 vs 0.0 SSB/day p=0.002).
      CONCLUSION: Even after adjustment for BMI, those of Maori and Pacific ethnicity
      have a significantly higher insulin response to fructose than New Zealand
      Europeans. Higher habitual SSB intake may be a contributing factor. This article
      is protected by copyright. All rights reserved.

PMID- 30298972
TI  - Twenty-Four-Hour Diet recall and Diet records compared with 24-hour urinary
      excretion to predict an individual's sodium consumption: A Systematic Review.
AB  - This systematic literature review aimed to investigate whether 24 hour diet
      recall and diet records are reliable and valid ways to measure usual dietary
      sodium intake compared with 24 hour urinary assessment. We searched electronic
      databases Medline, Embase, Cinahl, Lilacs, Google Scholar and the Cochrane
      Library using pre-defined terms Studies were eligible for inclusion if they
      assessed adult humans in free-living settings, and if they included dietary
      assessment and 24 hours urinary collection for assessment of sodium intake in the
      same participants. Studies that included populations with an active disease state
      that might interfere with normal sodium metabolism were excluded. Results of 20
      studies using 24 hour diet recall recall (including 14 validation studies) and 10
      studies using food records (including six validation studies) are included in
      this review. Correlations between estimates from dietary assessment and urinary
      excretion ranged from 0.16 to 0.72 for 24 hour diet recall, and 0.11 to 0.49 for
      food diaries. Bland-Altman analysis in two studies of 24 hour diet recall showed
      poor agreement with 24 hours urinary sodium excretion. These results show that 24
      hour diet recall and diet records inaccurately measure dietary sodium intake in
      individuals compared with the gold standard 24 hours urinary excretion.
      Validation studies of dietary assessment methods should include multiple days of
      assessment and 24 hours urine collection, use relevant food composition databases
      and Bland-Altman methods of analysis.

PMID- 30298973
TI  - Implementing the proclamation of stroke and potentially preventable dementias.
AB  - Brain health plays a central role in well-being and in the management of chronic
      diseases. Stroke and dementia pose the two greatest threats to brain health, but
      recent developments suggest the possibility that preventing stroke may also
      prevent some dementias: (a) A large population study showed a 32% decrease in the
      incidence of stroke and a concomitant 7% reduction in the incidence of dementia;
      (b) the treatment of atrial fibrillation resulted not only in stroke reduction,
      but also a 48% decrease in dementia; (c) the hypothesis-free analyses have shown
      that the first phase of Alzheimer disease involves vascular dysregulation,
      opening the door to new therapeutic approaches; (d) cognitive impairment, often
      treatable and reversible, accompanies heart and kidney failure. These
      developments, combined with the knowledge that stroke, dementia, and heart
      disease share the same major treatable risk factors, particularly hypertension,
      offer an opportunity for their joint prevention. This aspiration is expressed by
      a Proclamation of the World Stroke Organization on Stroke and Potentially
      Preventable Dementias and endorsed by the World Heart Federation, the World
      Hypertension League, Alzheimer Disease International, and 18 other international,
      regional, and national organizations as a call for action.

PMID- 30298974
TI  - Treatment adherence in systemic sclerosis: A cross-sectional study.
AB  - BACKGROUND: Treatment adherence is an important medical and pharmaco-economical
      phenomenon, influenced by multiple variables. Treatment adherence in systemic
      sclerosis (SSc) has been poorly studied. OBJECTIVE: The aim of the present study
      was to assess treatment adherence in SSc patients and to identify factors
      associated with good and poor adherence. METHODS: We conducted a monocentric,
      cross-sectional, observational study. Treatment adherence was evaluated by the
      Compliance Questionnaire of Rheumatology (CQR). The necessity of treatment and
      concerns about treatment were investigated using the Beliefs about Medicines
      Questionnaire-Specific (BMQ-S). The Illness Perception Questionnaire-Revised (IPQ
      R) assessed illness perceptions. Disease-related characteristics were collected
      retrospectively. RESULTS: A total of 66 patients were enrolled in this study. Of
      these, 47 (71.2%) had a weighted CQR score of <=80% ("poor adherence") and 19
      (28.8%) had a weighted CQR score of >80% ("good adherence"). No significant
      relationship between demographic, clinical or psychological factors and overall
      adherence could be found, except with the IPQ subscale "timeline acute/chronic"
      (p = 0.042). Our patient population estimated the necessity of their medication
      high (mean necessity score 20.5), with moderate concern beliefs (mean concern
      score 15.1). Subjective adherence, as self-reported by patients, was high.
      CONCLUSIONS: This study demonstrated low treatment adherence rates in SSc
      patients. We could not identify demographic, clinical or psychological factors
      associated with treatment adherence, except with the IPQ subscale "timeline
      acute/chronic". This suggests a correlation between poor adherence and the belief
      that the disease will be chronic without improvement over time. Symptom relief
      was an important motivating factor for taking medication. The treatment necessity
      was scored higher than treatment concerns, but the necessity beliefs were not
      associated with adherence.

PMID- 30298975
TI  - Electrochemical Reduction of Carbon Dioxide to Value-added Products: The
      Electrocatalyst and Microbial Electrosynthesis.
AB  - The electrochemical reduction of carbon dioxide (CO2 ) to value-added products
      obtains great attention and investigation worldwide in recent years. The
      commercialization of this green process relies on the progress of relating high
      performance electrocatalysts and their feasibility with proper reactor design.
      The microbial electrosynthesis (MES) is an alternative route to reduce CO2 with
      electroactive bio-film electrode as catalyst. This review presents the research
      status and development of cathode catalysts, particularly focusing on the active
      sites and development tendency, for highly efficient electrochemical reduction
      CO2 from personal viewpoint. Some of our results are also presented to exhibit
      contributions. MES shows a similar process to the typical electrochemical
      reduction of CO2 . Their combination is an important trend, and the future
      research in this field is full of challenges and opportunities.

PMID- 30298976
TI  - Are prothrombin time and clot waveform analysis useful in detecting a bleeding
      risk in liver cirrhosis?
AB  - INTRODUCTION: Prothrombin time is thought to be unreliable in cirrhotic patients
      to predict the risk of bleeding. We investigated whether prothrombin time ratio
      was an independent risk factor for bleeding alongside its clot waveform analysis.
      METHODS: We studied 307 consecutive cirrhotic patients and 115 healthy subjects.
      A coagulometer was used for detecting both prothrombin time and clot waveform
      analysis which included velocity (1st derivative) and acceleration (2nd
      derivative) of clot formation, and area of parabolic segment of the 1st and 2nd
      derivatives of prothrombin time (entire cycle of the clot formation). RESULTS:
      Logistic regression shows that prothrombin time ratio was the only variable
      significantly associated with the history of bleeding. Using a hemorrhagic score,
      the stepwise model included prothrombin time ratio and the area of parabolic
      segment of the 1st derivative of Prothrombin Time. Odds ratio was used to create
      a new score to be challenged against the hemorrhagic score in a ROC analysis. The
      AUC was 0.72, 95% CI: 0.67-0.77. CONCLUSION: Prothrombin time ratio is associated
      to an increased bleeding risk. Its role may be further emphasized considering
      clot waveform analysis. The new score, if aggregated to prothrombin time ratio,
      could be useful to provide a single parameter immediately ready to assess the
      bleeding risk in the individual cirrhotic patient.

PMID- 30298977
TI  - Cardiac pacing in cardioinhibitory syncope in children.
AB  - INTRODUCTION: Reflex vasovagal-or cardioinhibitory syncope is known to be a major
      cause of recurrent syncope in children. The mechanism of vasovagal syncope (VVS)
      is an interaction between a vagally mediated bradycardia or asystole and a more
      or less manifest vasodilatory component. Although pacing is not advisable as a
      standard approach in patients with VVS, it remains a treatment option of last
      resort in exceptionally severe cases, or patients with contraindication or
      refractoriness to drug therapy and life style changes. To effectively avoid VVS
      in these patients, the pacemaker has to both prevent bradycardia and to
      compensate for the vasodilatory component. Therefore, this study aimed to
      evaluate a simple pacemaker setting (VVI pacing with hysteresis) with the
      potential to prevent VVS in affected children. METHODS: Clinical data of
      patients, who were presented to the Department for Pediatric Cardiology, Heart
      Center Leipzig, in the period of 2001-2017 for cardiac pacemaker implantation for
      cardioinhibitory syncope or pallid breath-holding spells, were collected
      retrospectively. RESULTS: Eleven pediatric patients, median age 2.7 (0.8-17)
      years, were included. Pacemaker settings are depicted. In 10 out of 11 patients,
      an entire abolishment of syncope could be achieved (P = .002). CONCLUSION: The
      presented VVI pacing with hysteresis seems to be a promising pacemaker setting in
      pediatric patients with cardioinhibitory syncope who need a pacemaker.
      Unnecessary ventricular stimulation is effectively avoided, while cardiac output
      is preserved during cardioinhibition, by providing a sufficient paced heart rate,
      compensating for the often present vasodilatory component.

PMID- 30298978
TI  - Quantification of oleacein and oleuropein aglycone in olive oil using deuterated
      surrogates by normal-phase ultra high performance liquid chromatography with
      quadrupole time-of-flight mass spectrometry.
AB  - An analytical method for the analysis of relevant secoiridoid-based components in
      olive oil, oleacein and oleuropein aglycone, is described using for the first
      time deuterated surrogates. 0.2 g of sample was necessary to perform the analysis
      using liquid-liquid extraction and ultrasound-assisted extraction with a mixture
      of methanol/water (4:1, v/v). To avoid the formation of by-products, normal-phase
      ultra high performance liquid chromatography was chosen for the chromatographic
      separation. The selected mobile phase was a gradient mixture of tetrahydrofurane
      and hexane, and an ACE Excel 3 CN-ES column as stationary phase. The detection
      and quantification was performed with a SYNAPT G2-Si mass spectrometer. The
      calibration curves for oleacein and oleuropein aglycone were linear and
      quadratic, respectively. The validation was done at three levels of
      concentration. Relative errors from 0.1 to 10.5% and relative standard deviations
      lower than 9% were obtained. The method was applied to study different samples of
      olive oil.

PMID- 30298979
TI  - Corrigendum for Hudgins et al. (2017) https://doi.org/10.1111/ele.12741.

PMID- 30298980
TI  - Electrometer offset current due to scattered radiation.
AB  - Relative dose measurements with small ionization chambers in combination with an
      electrometer placed in the treatment room ("internal electrometer") show a large
      dependence on the polarity used. While this was observed previously for percent
      depth dose curves (PDDs), the effect has not been understood or preventable. To
      investigate the polarity dependence of internal electrometers used in conjunction
      with a small-volume ionization chamber, we placed an internal electrometer at a
      distance of 1 m from the isocenter and exposed it to different amounts of
      scattered radiation by varying the field size. We identified irradiation of the
      electrometer to cause a current of approximately -1 pA, regardless of the sign of
      the biasing voltage. For low-sensitivity detectors, such a current noticeably
      distorts relative dose measurements. To demonstrate how the current
      systematically changes PDDs, we collected measurements with nine ionization
      chambers of different volumes. As the chamber volume decreased, signal ratios at
      20 and 10 cm depth (M20/M10) became smaller for positive bias voltage and larger
      for negative bias voltage. At the size of the iba CC04 (40 mm3) the difference of
      M20/M10 was around 1% and for the smallest studied chamber, the iba CC003 chamber
      (3 mm3), around 7% for a 10 * 10 cm2 field. When the electrometer was moved
      further from the source or shielded, the additional current decreased.
      Consequently, PDDs at both polarities were brought into alignment at depth even
      for the 3 mm3 ionization chamber. The apparent polarity effect on PDDs and
      lateral beam profiles was reduced considerably by shielding the electrometer. Due
      to normalization the effect on output values was low. When measurements with a
      low-sensitivity probe are carried out in conjunction with an internal
      electrometer, we recommend careful monitoring of the particular setup by testing
      both polarities, and if deemed necessary, we suggest shielding the electrometer.

PMID- 30298981
TI  - Online peer consulting for health professionals.
AB  - BACKGROUND: Many health care professionals specialise in particular medical
      fields. Nevertheless, they often encounter patients with other indications for
      which they have only limited experience. In such situations it is helpful to
      consult colleagues who have specialised in the respective areas. The Internet
      provides the opportunity to connect with other specialists that can be used for
      peer consulting. We argue that health professionals should learn to make use of
      online peer consulting during vocational training. METHODS: We used an open
      source platform that provided the opportunity to chat and upload documents. We
      recruited 45 first-year physiotherapy students as participants. The training for
      online peer consulting was integrated into courses where students were taught
      basic principles of gait analysis and learned how to document the findings of
      their examinations. Subsequently, the students evaluated the course and the
      online collaboration. FINDINGS: Students were highly motivated to use the online
      platform and perceived the online peer consulting and the atmosphere of
      collaboration on the platform to be very positive. In addition, students had a
      significant increase in content knowledge and were more confident in their own
      knowledge than they were before the online peer consulting. DISCUSSION: It seems
      appropriate to provide training for giving and gathering online peer feedback.
      This opportunity, provided at an early stage of training, could help prepare
      students for continuing co-operative exchange in their professional lives. Health
      care professionals should learn how to gather information from colleagues and how
      to provide adequate feedback.

PMID- 30298982
TI  - Brief teaching sessions change behaviour in A&E.
AB  - BACKGROUND: The Accident and Emergency Department (A&E) is a busy environment
      that requires time- and resource-efficient teaching. Managing cervical spine (c
      spine) trauma is often an unfamiliar skill for new doctors starting work in A&E.
      This study investigated the efficacy of brief teaching interventions in changing
      clinician behaviour within A&E. The Accident and Emergency Department is a busy
      environment that requires time- and resource-efficient teaching METHODS: Data for
      482 patients receiving c-spine computed tomography (CT) imaging in two
      Gloucestershire A&Es before and after multimodal departmental teaching were
      compared. Time taken to CT, indication for CT scan and presence of bony injury
      were manually recorded from patient management software. RESULTS: Following the
      provision of teaching, the proportion of CT scans performed within 1 hour did not
      significantly change, from 31% before teaching to 37.6% after teaching (p =
      0.133); however, the mean number of c-spine CT scans performed per week rose from
      14.50 to 23.25 (p = 0.0001), and the mean number of CT scans performed per week
      within 1 hour rose from 4.50 to 8.75 (p <= 0.001). There was no reduction in the
      quality of these scans, with the proportion detecting bony injury remaining
      constant, and there was no increase in the proportion of scans not indicated by
      National Institute for Health and Care Excellence guidelines. CONCLUSIONS: This
      study demonstrates that brief, low-resource teaching can be associated with a
      positive change in clinician behaviour. This intervention was straightforward to
      implement and is likely to be transferable to other guideline-driven
      investigations. Limitations include the patient cohort being proportionately
      older than that found in major trauma centres, and a lack of data on patients in
      whom CT scans were indicated but not performed.

PMID- 30298983
TI  - The utility of combined cardiopulmonary exercise stress testing in the evaluation
      of pediatric patients with chest pain.
AB  - INTRODUCTION: A cardiac cause is an extremely rare etiology of pediatric chest
      pain. Despite its low sensitivity/specificity, exercise stress testing (EST) is
      widely used to determine the prognosis in patients with suspected/established
      coronary disease. We aimed to look at the utility of a combined cardiopulmonary
      EST in the evaluation of pediatric patients with chest pain. METHODS: After
      institutional review board approval, a retrospective chart review was performed
      of all pediatric patients who were referred for an EST for chest pain from
      January 2014 to 2017. Patients with incomplete records, severe congenital heart
      disease, and a prior EST were excluded. RESULTS: A total of 389 patients met the
      inclusion criteria. Echocardiogram (ECHO) was performed on 333 (85.6%) patients
      and 43 (11%) previously unknown structural cardiac anomalies were identified. A
      total of 76 (19.5%) patients had an abnormal EST with the 3 most common causes
      being related to the respiratory system. Only four patients had both an abnormal
      exercise stress test and an incidental structural anomaly on ECHO but none of
      them had their symptoms recreated during the EST. CONCLUSION: Only 1% of patients
      previously undiagnosed with heart disease had an abnormal stress test and an
      incidental anomaly on ECHO. These ECHO anomalies were unlikely to be the cause of
      chest pain. Furthermore, since the majority of abnormal stress tests were
      secondary to a pulmonary cause, a complete cardiopulmonary EST may be an
      effective screening tool for certain patients presenting with chest pain. Our
      study emphasizes the need for performing a complete cardiopulmonary EST instead
      of an isolated cardiac stress test to maximize diagnostic efficiency and yield.

PMID- 30298985
TI  - Educate students about human factors in acute care.

PMID- 30298984
TI  - Practical advice for selecting or determining trophic magnification factors for
      application under the European Union Water Framework Directive.
AB  - European Union Directive 2013/39/EU, which amended and updated the Water
      Framework Directive (WFD; 2000/60/EC) and its daughter directive (2008/105/EC),
      sets Environmental Quality Standards for biota (EQSbiota ) for a number of
      bioaccumulative chemicals. These chemicals pose a threat to both aquatic wildlife
      and human health via the consumption of contaminated prey or the intake of
      contaminated food originating from the aquatic environment. EU member states will
      need to establish programs to monitor the concentration of 11 priority substances
      in biota and assess compliance against these new standards for the classification
      of surface water bodies. An EU-wide guidance effectively addresses the
      implementation of EQSbiota . Flexibility is allowed in the choice of target
      species used for monitoring to account for both diversity of habitats and aquatic
      community composition across Europe. According to that guidance, the consistency
      and comparability of monitoring data across member states should be enhanced by
      adjusting the data on biota contaminant concentrations to a standard trophic
      level by use of the appropriate trophic magnification factor (TMF), a metric of
      contaminant biomagnification through the food web. In this context, the selection
      of a TMF value for a given substance is a critical issue, because this field
      derived measure of trophic magnification can show variability related to the
      characteristics of ecosystems, the biology and ecology of organisms, the
      experimental design, and the statistical methods used for TMF calculation. This
      paper provides general practical advice and guidance for the selection or
      determination of TMFs for reliable application within the context of the WFD
      (i.e., adjustment of monitoring data and EQS derivation). Based on a series of
      quality attributes for TMFs, a decision tree is presented to help end users
      select a reasonable and relevant TMF. Integr Environ Assess Manag 2018;00:00-00.
      (c) 2018 The Authors. Integrated Environmental Assessment and Management
      published by Wiley Periodicals, Inc. on behalf of Society of Environmental
      Toxicology & Chemistry (SETAC).

PMID- 30298986
TI  - Solvate Ionic Liquids for Li, Na, K, and Mg Batteries.
AB  - From the viewpoint of element strategy, non-Li batteries with promising negative
      and positive electrodes have been widely studied to support a sustainable
      society. To develop non-Li batteries having high energy density, research on
      electrolyte materials is pivotal. Solvate ionic liquids (SILs) are an emerging
      class of electrolytes possessing somewhat superior properties for battery
      applications compared to conventional ionic liquid electrolytes. In this account,
      we describe our recent efforts regarding SIL-based electrolytes for Li, Na, K,
      and Mg batteries with respect to structural, physicochemical, and electrochemical
      characteristics. Systematic studies based on crystallography and Raman
      spectroscopy combined with thermal/electrochemical stability analysis showed that
      the balance of competitive cation-anion and cation-solvent interactions
      predominates the stability of the solvate cations. We also demonstrated battery
      applications of SILs as electrolytes for non-Li batteries, particularly for Na
      batteries.

PMID- 30298987
TI  - Right thoracotomy for aortic valve replacement in the adolescents with bicuspid
      aortic valve.
AB  - BACKGROUND: In this study, we compared our experience about early and midterm
      follow-up outcomes for right anterolateral minithoracotomy (RAMT) vs full
      sternotomy (FS) in surgical aortic valve replacement (AVR) among adolescents with
      bicuspid aortic valve (BAV). METHODS: Patients were retrospectively enrolled from
      January 2008 to December 2017. Inclusion criteria were patients with BAV who had
      to undergo to AVR. They were divided in two groups: RAMT and FS. The choice of
      RAMT was based on individual surgeon's preferences or when expressly requested by
      patient that was informed of nonconventional approach. RESULTS: We enrolled 61
      patients, 23 in RAMT group and 38 in FS group. The mean age was 15.6 +/- 1.7
      years for RAMT group and 16.1 +/- 1.5 years for FS group (P = .23). The RAMT
      group had a higher prevalence of female gender (P = .04). The patients in the
      RAMT group had longer cardiopulmonary bypass (115.2 +/- 18.5 vs 102.2 +/- 16.5
      min; P = .006) and cross-clamp time (78.6 +/- 18.1 vs 74.3 +/- 15.2 min; P =
      .01). No patients required intraoperative conversion to FS. No differences were
      found in ventilation times, postoperative intensive care unit (ICU), and hospital
      length of stay for both groups. Follow-up echocardiograms were available for all
      patients at median of 5.2 years (range 0.5-9.6 years, median 5.4 years for RAMT
      and 5.1 for FS) and no patient required reoperation for aortic prosthesis
      malfunction. CONCLUSIONS: Our study shows that RAMT is safe and effective as FS.
      Although the RAMT operation takes slightly more operation time, it is not
      associated with major adverse effects.

PMID- 30298988
TI  - Preparation of mesoporous silica nanoparticles molecularly imprinted polymer for
      efficient separation and enrichment of perfluorooctane sulfonate.
AB  - As a persistent organic pollutant, perfluorooctane sulfonate has drawn a
      worldwide attention. In this contribution, a novel molecularly imprinted polymer
      based on mesoporous silica nanoparticles was prepared for efficient separation
      and enrichment of perfluorooctane sulfonate in water samples. The polymer was
      characterized by transmission electron microscopy, Fourier transform infrared
      spectroscopy, X-ray diffraction, and N2 adsorption/desorption experiments. The
      static adsorption experiments and the adsorption kinetic tests were conducted.
      The results showed that the adsorbents had high adsorption capacity (21.10 mg/g)
      and short adsorption equilibration time (25 min). Meanwhile, the effect of
      mesoporous silica nanoparticles on the adsorption capacity was investigated. The
      results indicated that the mesoporous structure helped to increase the adsorption
      capacity of adsorbent to adsorbate. Besides, the adsorbents show good specificity
      and good reusability with the adsorption capacity of adsorbent toward
      perfluorooctane sulfonate decreasing <5% after five adsorption-desorption cycles.
      The mesoporous silica nanoparticles molecularly imprinted polymer has been used
      successfully for the removal of perfluorooctane sulfonate in environmental water
      samples with relative standard deviation <=4.64%.

PMID- 30298989
TI  - Analysis of insulin and insulin analogs from dried blood spots by means of liquid
      chromatography-high resolution mass spectrometry.
AB  - While dried blood spot (DBS) analysis concerning low molecular mass molecules has
      become more and more established in various fields of analytical chemistry, the
      utility of DBS in determining peptides and proteins from DBS is yet comparably
      limited. In consideration of the fact that the apparent benefits of DBS sampling
      are similar for analytes of lower and higher molecular mass, dedicated (non
      generic) sample preparation procedures are required that meet the needs for
      detecting peptidic drugs and hormones in DBS. The analysis of insulin and its
      synthetic analogs by mass spectrometry has received increased attention in
      several fields such as doping controls, forensics, and drug metabolism and
      pharmacokinetics studies. Hence, a strategy facilitating the analysis of insulin
      and its synthetic or animal analogs (human, Lispro, Aspart, Glulisine, Glargine,
      Detemir, Tresiba, and porcine and bovine insulin) from DBS was developed. The
      successful analysis of these substances at physiologically relevant
      concentrations was realized after ultrasonication-assisted extraction,
      immunoaffinity purification, and liquid chromatographic separation followed by
      high resolution mass spectrometric detection (with or without ion mobility).
      Assay validation demonstrated adequate sensitivity (LOD 0.5 ng/mL for most
      insulins), as well as precise (< 25%) and reproducible results for all included
      target insulins. Additionally, proof-of-principle data were obtained by the
      analysis of DBS samples obtained from healthy volunteers in non-fasting state as
      well as a sample from a diabetic volunteer treated with the fast acting analog
      insulin Aspart.

PMID- 30298990
TI  - Factors associated with patients' willingness to consider joint surgery after
      completion of a digital osteoarthritis treatment program: A prospective cohort
      study.
AB  - OBJECTIVES: To examine patient willingness and possible shift in willingness for
      surgery and to investigate factors associated with this shift, following
      participation in the digital non-surgical osteoarthritis (OA) treatment program
      Joint Academy. METHODS: 458 individuals (mean age 62+/-5.6 years, 67% women) with
      diagnosed hip or knee were evaluated after six weeks in Joint Academy, comprising
      education and exercise as well as asynchronous chat with a physical therapist.
      Data describing joint pain, health-related quality of life (EQ-5D-3L), walking
      difficulties, 30-second Chair Stand Test (30CST) and willingness to consider
      surgery were collected at baseline and at six weeks. RESULTS: At follow-up, 31%
      of those willing to consider surgery at baseline no longer considered surgery. Of
      those who were unwilling to consider surgery at baseline, 6% re-considered and
      considered surgery at follow-up. Less pain and a higher EQ-5D-3L index at six
      weeks were associated with the shift from being willing to unwilling to consider
      surgery at follow-up (OR=0.67-1.64, p<0.05). Worse pain, a lower EQ-5D-3L index
      and having walking difficulties at six weeks, and a lower pain and EQ-5D-3L index
      improvement were associated with the shift from being unwilling to willing to
      consider surgery at six weeks (OR=0.51-4.30, p<0.005). CONCLUSIONS: Evidence
      based non-surgical OA treatment, at least delivered digitally, may reduce the
      need for surgery and should therefore be offered as the first-line treatment
      option to patients with hip and knee OA. Result also supports the notion that
      such treatment programs have the potential to improve selection of patients for
      total joint replacement. This article is protected by copyright. All rights
      reserved.

PMID- 30298991
TI  - An Integrated Approach to Aggregate Control for Therapeutic Bispecific Antibodies
      Using an Improved Three Column Mab Platform-Like Purification Process.
AB  - Single chain variable fragment-IgGs (scFv-IgG) are a class of bispecific
      antibodies consisting of two single chain variable fragments (scFv) that are
      fused to an intact IgG molecule. A common trend observed for expression of scFv
      IgGs in mammalian cell culture is a higher level of aggregates (10%-30%) compared
      to mAbs, which results in lower purification yields in order to meet product
      quality targets. Furthermore, the high aggregate levels also pose robustness
      risks to a conventional mAb three column platform purification process which uses
      only the polishing steps (e.g., cation exchange chromatography [CEX]) for
      aggregate removal. Protein A chromatography with pH gradient elution, high
      performance tangential flow filtration (HP-TFF) and calcium phosphate
      precipitation were evaluated at the bench scale as means of introducing
      orthogonal aggregate removal capabilities into other aspects of the purification
      process. The two most promising process variants, namely Protein A pH gradient
      elution followed by calcium phosphate precipitation were evaluated at pilot
      scale, demonstrating comparable performance. Implementing Protein A
      chromatography with gradient elution and/or calcium phosphate precipitation
      removed a sufficient portion of the aggregate burden prior to the CEX polishing
      step, enabling CEX to be operated robustly under conditions favoring higher
      monomer yield. From starting aggregate levels ranging from 15% to 23% in the
      condition media, levels were reduced to between 2% and 3% at the end of the CEX
      step. The overall yield for the optimal process was 71%. Results of this work
      suggest an improved three-column mAb platform-like purification process for
      purification of high aggregate scFv-IgG bispecific antibodies is feasible. (c)
      2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018.

PMID- 30298992
TI  - Biosynthesis of Au nanoparticles by a marine bacterium and enhancing their
      catalytic activity through metal ions and metal oxides.
AB  - We report that a marine Shewanella sp. CNZ-1 is capable of producing Au NPs under
      various conditions. Results showed that initial concentration of Au[III], pH
      values and electron donors affected nucleation of Au NPs by CNZ-1, resulting in
      different apparent color of the as-obtained bio-Au NPs, which were further
      characterized by UV-Vis, TEM, XRD and XPS analyses. Mechanism studies revealed
      that Au[III] was first reduced to Au[I] and eventually reduced to EPS-coated Au0
      NPs. FTIR and FEEM analyses revealed that some amides and humic acid-like matters
      were involved in the production of bio-Au NPs through CNZ-1 cells. In addition,
      we also found that the catalytic activity of bio-Au NPs for 4-nitrophenol (4-NP)
      reduction could be enhanced by various metal ions (Ca2+ , Cu2+ , Co2+ , Fe2+ ,
      Fe3+ , Ni2+ , Sr2+ and Cr3+ ) and metal oxides (Fe3 O4 , Al2 O3 and SiO2 ), which
      is beneficial for their further practical application. The maximum zero-order
      rate constant k1 and first-order rate constant k2 of all metal ions/oxides
      supplemented systems can reach 99.65 mg/(L. min) and 2.419 min-1 , which are 11.3
      and 12.6-fold higher than that of control systems, respectively. This article is
      protected by copyright. All rights reserved.

PMID- 30298993
TI  - A rAAV2-producing yeast screening model to identify host proteins enhancing rAAV
      DNA replication and vector yield.
AB  - Recombinant adeno-associated viral vectors (rAAV) are promising therapies for
      genetic diseases. Although current platforms for recombinant vector production
      can generate drug material for pre-clinical and clinical studies, rAAV
      biomanufacturing will eventually face commercial supply challenges if per cell
      vector productivity and process scalability are not improved. Because
      considerable efforts have traditionally focused on optimizing rAAV plasmid
      design, herein we investigate the impact of host cell proteins on vector
      production to identify proteins that may enhance rAAV yield. Using a rAAV2-GFP
      producing Saccharomyces cerevisiae model in combination with the yeast Tet Hughes
      Collection screening library, we identified 22 gene candidates that improved rAAV
      DNA replication (rAAV-GFP/18s rDNA ratio) and vector yield (benzonase-resistant
      rAAV DNA vector genome titer) as high as 6-fold and 15-fold relative to control,
      respectively. The candidate proteins participate in biological processes such as
      DNA replication, ribosome biogenesis, and RNA and protein processing. The best
      five candidates (PRE4, HEM4, TOP2, GPN3, and SDO1) were further screened by
      generating overexpression mutants in the YPH500 yeast strain. Subsequent clone
      evaluation was performed to confirm the rAAV-promoting activity of selected
      candidates under plate-based and bioreactor-controlled fermentation conditions.
      Digital droplet PCR analysis of cell lysate and AVB resin-purified material
      confirmed HEM4 and TOP2 overexpression mutants displayed the highest per cell
      total rAAV DNA productivity (1.6 and 1.7-fold increase over control,
      respectively) and per cell vector productivity (3 and 4-fold over control,
      respectively). This evaluation confirmed that overexpression of HEM4 and TOP2
      proteins enhanced total and benzonase-resistant rAAV DNA yield. Further studies
      are needed to understand their mechanism of action and to assess their potential
      application in molecular strategies for rAAV production. (c) 2018 American
      Institute of Chemical Engineers Biotechnol. Prog., 2018.

PMID- 30298994
TI  - High-throughput screening of antibody-expressing CHO clones using an automated
      shaken deep-well system.
AB  - Biopharmaceutical protein manufacturing requires the highest producing cell lines
      to satisfy current multiple grams per liter requirements. Screening more clones
      increases the probability of identifying the high producers within the pool of
      available transfectant candidate cell lines. For the predominant industry
      mammalian host cell line, Chinese hamster ovary (CHO), traditional static-batch
      culture screening does not correlate with the suspension fed-batch culture used
      in manufacturing, and thus has little predictive utility. Small scale fed-batch
      screens in suspension culture correlate better with bioreactor processes but a
      limited number of clones can be screened manually. Scaled-down systems, such as
      shaken deep well plates, combined with automated liquid handling, offer a way for
      a limited number of scientists to screen many clones. A statistical analysis
      determined that 384 is the optimal number of clones to screen, with a 99%
      probability that six clones in the 95th percentile for productivity are included
      in the screen. To screen 384 clones efficiently by the predictive method of
      suspension fed-batch, the authors developed a shaken deep-well plate culturing
      platform, with an automated liquid handling system integrating cell counting and
      protein titering instruments. Critical factors allowing deep-well suspension
      culture to correlate with shake flask culture were agitation speed and culture
      volume. Using our automated system, one scientist can screen five times more
      clones than by manual fed-batch shake-flask or shaken culture tube screens and
      can identify cell lines for some therapeutic protein projects with production
      levels greater than 6 g/L.

PMID- 30298995
TI  - Shift to High-Intensity, Low-Volume Perfusion Cell Culture Enabling a Continuous,
      Integrated Bioprocess.
AB  - In order to address the increasing demand for biologics, cell culture
      intensification using perfusion offers significantly higher productivities while
      also reducing manufacturing costs, especially when part of an integrated,
      continuous bioprocess. An initial study of a long-duration perfusion process
      using a cell-bleed to maintain a target cell density observed a 2.1-fold higher
      cell-specific productivity and a gradual decline in the culture growth rate when
      perfused at an overall lower rate. Subsequent studies sought an alternative
      process that largely reduced the overall volume of media needed by first
      perfusing at a high cell-specific perfusion rate (CSPR) to support a high cell
      density followed by continued perfusion at a low CSPR to promote a more
      productive stationary phase. This high intensity, low-volume perfusion (HILVOP)
      process achieved cumulative volumetric productivities of 1.5-1.6 g/L/day with two
      CHO cell lines. When compared to each cell line's respective commercial-ready,
      fed-batch process, a 3.1-3.8-fold productivity increase was demonstrated while
      yielding similar product quality. Furthermore, the higher productivity achieved
      with HILVOP used 6.6-12.3-fold less media than a similarly productive long
      duration process. (c) 2018 American Institute of Chemical Engineers Biotechnol.
      Prog., 2018 (c) 2018 American Institute of Chemical Engineers Biotechnol. Prog.,
      2018.

PMID- 30298996
TI  - Post hoc analyses of SHIFT and PARADIGM-HF highlight the importance of chronic
      Chagas' cardiomyopathy Comment on: "Safety profile and efficacy of ivabradine in
      heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT
      trial" by Bocchi et al.

PMID- 30298997
TI  - Reply: Sacubitril/valsartan for Chagas' heart disease heart failure?

PMID- 30298998
TI  - Exploring the separation power of mixed-modal resins for purification of
      recombinant osteopontin from clarified Escherichia coli lysates.
AB  - Osteopontin (OPN) is a structural protein with potential value in therapeutic and
      diagnostic applications. Low titer, acidic isoelectric point, and the lack of
      well-defined secondary and tertiary structure were some of the challenges that
      complicated purification development of OPN from recombinant Escherichia coli
      lysates. Reported processes for OPN recovery from recombinant sources use
      nonorthogonal unit operations and often suffer from low yield. In this work, we
      expanded the search for an optimal OPN purification method by including mixed
      modal resins with both ionic and hydrophobic properties (Capto adhere, HEA
      HyperCel, and PPA HyperCel). Plate-based high-throughput screening (HTS) platform
      revealed useful information about the interactions between the three different
      ligands and OPN as function of pH and ionic strength. The HTS data allowed the
      selection of OPN adsorption and elution conditions that were tested and optimized
      in a batch mode. In terms of purification factor and yield, HEA HyperCel
      performed significantly better than the other two mixed-modal resins. Pairing HEA
      HyperCel with a strong anion exchange step (Capto Q) resulted in a two-step
      purification process that achieved 45-fold purification of OPN with a final
      purity of 95% and 44% overall yield. The orthogonality provided by mixed-modal
      and ion exchange steps resulted in higher yield in fewer unit operations than
      reported processes. (c) 2018 American Institute of Chemical Engineers Biotechnol.
      Prog., 2018.

PMID- 30298999
TI  - Total saponins from the leaves of Panax notoginseng inhibit depression on mouse
      chronic unpredictable mild stress model by regulating circRNA expression.
AB  - OBJECTIVES: Total saponins from the leaves of Panax notoginseng saponins (SLPN)
      could inhibit development of depression, but the underlying mechanisms remains
      unclear. This study aimed to address the roles of circular RNAs in depression
      inhibition by SLPN. METHODS: The mouse chronic unpredictable mild stress (CUMS)
      model was established, which were confirmed by mouse weight, forced swimming test
      (FST) and tail suspension test (TST). Effects of SLPN on depression were
      evaluated in CUMS through these same assays. Circular RNA profiles in mouse
      ventral medial prefrontal cortex (VMPC) and hippocampus of CUMS mice were
      determined by high-through sequencing, followed by confirmation via qRT-PCR.
      Overexpression of mmu_circ_0001223 was done by transfection of PC12 cell through
      lentiviral system. Protein abundances of cAMP response element binding protein
      1(CREB1) and brain-derived neurotrophic factor (BDNF) were evaluated by western
      blotting. RESULTS: Mouse body weight, immobility time in FST and immobility time
      in TST of CUMS mice were significantly recovered by SLPN treatment. A large
      number of circular RNAs were differentially expressed in the ventral medial
      prefrontal cortex (VMPC) and hippocampus tissues of CUMS mice. Among them,
      mmu_circ_0001223 expression was greatly decreased in CUMS mice, but significantly
      elevated by SLPN treatment. The protein levels of CREB1 and BDNF were also
      remarkably promoted in CUMS mice by treatment of SLPN. Overexpression of
      mmu_circ_0001223 enhanced CREB1 and BDNF protein levels in PC12 cells.
      CONCLUSION: SLPN regulate the expression of large number circular RNAs in CUMS
      mice, which might be important mediators of SLPN's anti-depression effects.

PMID- 30299000
TI  - Hydrolysis of Lipid-Extracted Chlorella vulgaris by Simultaneous Use of Solid and
      Liquid Acids.
AB  - Microalgal biomass was hydrolyzed using a solid acid catalyst with the aid of
      liquid acid. The use of solid acid as the main catalyst instead of liquid acid
      was to omit subsequent neutralization and/or desalination steps, which are
      commonly required in using the resulting hydrolysates for microbial fermentation.
      The hydrolysis of 10 g/L of lipid-extracted Chlorella vulgaris containing 12.2%
      carbohydrates using 7.6 g/L Amberlyst 36 and 0.0075 N nitric acid at 150 degrees
      C resulted in 1.08 g/L of mono-sugars with a yield of 88.5%. For hydrolysis of
      higher concentrations of the biomass over 10 g/L, the amount of Amberlyst 36
      needed to be increased in proportion to the biomass concentration to maintain
      similar levels of hydrolysis performance. Increasing the solid acid concentration
      protected the surface of the solid acid from being severely covered by cell
      debris during the reaction. A hydrolysate of lipid-extracted C. vulgaris 50 g/L
      was used, with no post-treatment of desalination, for the cultivation of
      Klebsiella oxytoca producing 2,3-butanediol. Cell growth in the hydrolysate was
      found to be almost the same as in the conventional medium with the same
      monosaccharide composition, confirming its fermentation compatibility. It was
      noticeable that the yield of 2,3-butanediol with the hydrolysate was observed to
      be 2.6 times higher than that with the conventional medium. (c) 2018 American
      Institute of Chemical Engineers Biotechnol. Prog., 2018.

PMID- 30299002
TI  - Differences between stance and foot preference evident in Osprey (Pandion
      haliaetus) fish holding during movement.
AB  - BACKGROUND: Skateboarders, snowboarders, and surfers all show stance preferences
      for which foot is forward while moving. We are unaware of other animals than
      humans with a stance preference, perhaps excepting Osprey, who fly their caught
      fish beneath them in a foot-forward stance. We hypothesize there should be no
      difference between left foot forward, right foot back (conventional) versus right
      foot forward left foot back (goofy) stances or for fish holding with unilateral
      left or right foot. Online, publicly available, convenience images of Osprey
      catching fish were accessed and assessed by five independent reviewers using
      different Internet search engines or online photo series. Stance preference and
      footedness were tested using chi-square analysis. RESULTS: Stance preferences
      were evident with the left foot forward (conventional stance) on average 64-78%
      of the time (all p < 0.02). No difference in foot preference for either one-foot
      grabs of fish during flight or for non-flight nest/perch fish holding was
      evident. CONCLUSION: Flight stance of Osprey holding fish shows a lateralized
      preference in a proportion similar to skateboarders of surfers. We discuss stance
      preferences in the setting of complex movements and potential flight and survival
      advantages for Osprey.

PMID- 30299003
TI  - Efficient and green aqueous-solid system for transphosphatidylation to produce
      phosphatidylhydroxybutyrate: Potential drugs for central nervous system's
      diseases.
AB  - The synthesis of nonnatural phospholipid, phosphatidylhydroxybutyrate (PB), was
      firstly introduced by phospholipase D (PLD)-mediated transphosphatidylation of
      phosphatidylcholine (PC) with sodium gamma-hydroxybutyrate (NaGHB) in the aqueous
      solid system. Nanoscale silicon dioxide (NSD) was employed as a carrier to
      provide an "artificial interphase" between PC and PLD. Special attention has been
      paid to the effect of the PC coverage on the surface area of hybrids of NSD-PC,
      the PC loading and the yield of PB. Results indicated that the highest PC loading
      of 98.3% and the highest PB yield of 97.3% were achieved. In addition, the free
      PLD in the aqueous-solid system showed the greater stability and pH tolerance
      than that in the traditional liquid-liquid system. The operational stability of
      free PLD solution was investigated. The yield of PB remained 70.7% after being
      used for five batches. The authors provide a new idea for drug design and the
      potential source of PB for medical experiments. PB is a potential drug and may
      have the excellent performance in the treatment of central nervous system's
      diseases. (c) 2018 American Institute of Chemical Engineers Biotechnol. Prog.,
      2018.

PMID- 30299004
TI  - Purification of a Bacteriocin-Like Inhibitory Substance Derived from Pediococcus
      acidilactici Kp10 by an Aqueous Micellar Two-Phase System.
AB  - Aqueous micellar two-phase system (AMTPS) is an extractive technique of
      biomolecule, where it is based on the differential partitioning behavior of
      biomolecule between a micelle-rich and a micelle-poor phase. In this study, an
      AMTPS composed of a nonionic surfactant, Triton X-100 (TX-100) was used for
      purifying a bacteriocin-like inhibitory substance (BLIS) derived from Pediococcus
      acidilactici Kp10. The influences of the surfactant concentration and the effect
      of additives on the partitioning behavior and activity yield of the BLIS were
      investigated. The obtained coexistence curves showed that the mixtures of
      solutions composed of different surfactant concentrations (5-30% w/w) and 50% w/w
      crude load were able to separate into two phases at temperatures of above 60 
      degrees C. The optimum conditions for BLIS partitioning using the TX-100-based
      AMTPS were: TX-100 concentration of 22.5% w/w, CFCS load of 50% w/w, incubation
      time of 30 min at 75  degrees C, and back-extraction using acetone precipitation.
      This optimal partitioning resulted in an activity yield of 64.3% and a
      purification factor of 5.8. Moreover, the addition of several additives, such as
      sorbitol, KCl, dioctyl sulfosuccinate sodium salt, and Coomassie(r) Brilliant
      Blue, demonstrated no improvement in the BLIS separation, except for Amberlite(r)
      resin XAD-4, where the activity yield was improved to 70.3% but the purification
      factor was reduced to 2.3. Results from this study have demonstrated the
      potential and applicability of TX-100-based AMTPS as a primary recovery method
      for the BLIS from a complex fermentation broth of P. acidilactici Kp10. (c) 2018
      American Institute of Chemical Engineers Biotechnol. Prog., 2018 (c) 2018
      American Institute of Chemical Engineers Biotechnol. Prog., 2018.

PMID- 30299006
TI  - Compassion in emergency departments. Part 3: enabling and supporting delivery of
      compassionate care.
AB  - In the final part of this three-part series, David Hunter and colleagues analyse
      the factors that enable and support delivery of compassionate care in emergency
      departments (EDs). Part one reported findings from doctoral-level research that
      explored nursing students' experiences of compassionate care in EDs, while part
      two considered the barriers to such care identified by the students. This article
      highlights and celebrates the ways in which emergency nurses provide
      compassionate care despite the challenges they face.

PMID- 30299005
TI  - Transient CHO expression platform for robust antibody production and its enhanced
      N-glycan sialylation on therapeutic glycoproteins.
AB  - Large-scale transient expression in mammalian cells is a rapid protein production
      technology often used to shorten overall timelines for biotherapeutics drug
      discovery. In this study we demonstrate transient expression in a Chinese hamster
      ovary (CHO) host (ExpiCHO-STM) cell line capable of achieving high recombinant
      antibody expression titers, comparable to levels obtained using human embryonic
      kidney (HEK) 293 cells. For some antibodies, ExpiCHO-STM cells generated protein
      materials with better titers and improved protein quality characteristics (i.e.,
      less aggregation) than those from HEK293. Green fluorescent protein imaging data
      indicated that ExpiCHO-STM displayed a delayed but prolonged transient protein
      expression process compared to HEK293. When therapeutic glycoproteins containing
      non-Fc N-linked glycans were expressed in transient ExpiCHO-STM, the glycan
      pattern was unexpectedly found to have few sialylated N-glycans, in contrast to
      glycans produced within a stable CHO expression system. To improve N-glycan
      sialylation in transient ExpiCHO-STM, we co-transfected galactosyltransferase and
      sialyltransferase genes along with the target genes, as well as supplemented the
      culture medium with glycan precursors. The authors have demonstrated that co
      transfection of glycosyltransferases combined with medium addition of galactose
      and uridine led to increased sialylation content of N-glycans during transient
      ExpiCHO-STM expression. These results have provided a scientific basis for
      developing a future transient CHO system with N-glycan compositions that are
      similar to those profiles obtained from stable CHO protein production systems.
      (c) 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018.

PMID- 30299007
TI  - Enhancing the recruitment and retention of overseas nurses from Kerala, India.
AB  - In September 2016, a team of nurses from East and North Hertfordshire NHS Trust
      (ENHT) and the University of Hertfordshire in England travelled to Kerala, India
      to interview and recruit nurses for the trust's acute hospital. Before
      undertaking the interviews, the team visited a nursing college and two hospitals.
      Based on the findings from these visits and from meeting the interview
      candidates, the team designed a bespoke mentoring programme for Keralan nurses
      recruited to ENHT to ease the transition into nursing and living in the UK. This
      article explores the challenges associated with recruiting and retaining nurses
      from overseas, and discusses how these can be addressed to ensure that these
      nurses practise safely and are supported effectively.

PMID- 30299008
TI  - ANSI/ISEA 105-2016 Regulation Updates.
AB  - We're better equipped than ever before to provide hand protection to industrial
      workers. The biggest challenge is making sure regulations and standards around
      PPE and hand protection keep pace.

PMID- 30299009
TI  - Safer Soap: A Look at Harmful Ingredients Found in Hand Cleansers
AB  - According to the Centers for Disease Control and Prevention, up to 40 percent of
      workers will suffer from occupational dermatitis at some point in their working
      lives.

PMID- 30299010
TI  - Key Requirements for Employees Transporting Hazmats.
AB  - Like OSHA and EPA chemical safety trainings, DOT training helps hazmat employees
      to recognize and identify hazardous materials and learn how their functions
      ensure that those materials can be transported safely.

PMID- 30299011
TI  - Your Eyes Are Amazing-They Deserve Quality PPE.
AB  - When vision is impaired, quality of life and the ability to work experience a
      drastic and unfortunate decline. Preventing eye injuries should be a top task on
      every safety professional's to-do list.

PMID- 30299012
TI  - Safety Eyewear for Computer Vision Syndrome.
AB  - Computer work is more visually demanding than any other type of office work.

PMID- 30299013
TI  - How Protective Eyewear Has Changed Dramatically Over the Decades.
AB  - Today's safety eyewear can be so lightweight and comfortable that at times
      workers don't even notice they are wearing it once it's on.

PMID- 30299014
TI  - Why Leadership Development Efforts Will Continue to Fail.
AB  - Profile your desired leader. What would you see them doing or hear them saying
      that indicates they are in the right position and a change-agent?

PMID- 30299015
TI  - Second Circle Leadership.
AB  - Disconnected leaders are typically stymied when it comes to sensing trends of
      change, making effective plans, deeply motivating others, and implementing game
      changing actions.

PMID- 30299016
TI  - [Antiplatelet therapy in cardiology].
AB  - Platelets are important components of hemostasis and play a key role in the
      formation of atherothrombosis. Rupture or erosion of atherosclerotic plaque gives
      rise to a thrombus with the involvement of platelets. Antiplatelet agents are
      instrumental in preventing the development of atherothrombosis of different
      localization, including coronary arteries.

PMID- 30299018
TI  - [Comorbidity in rheumatoid arthritis: A focus on cardiovascular diseases].
AB  - Cardiovascular diseases (CVD) in patients with rheumatoid arthritis (RA) are
      ranked first in the structure of comorbidity and mortality. This review includes
      recent data on common pathogenic mechanisms of inflammation and atherosclerosis,
      the impact of traditional and specific risk factors, biomarkers of CVD in RA
      patients. Variants of CVD in RA, the possible pathogenic mechanisms of their
      development and methods of diagnosis and prevention are described.

PMID- 30299017
TI  - [Microvascular angina. Modern aspects of pathogenesis, diagnostics and
      treatment].
AB  - Microvascular angina was included in the European guidelines on the management of
      patients with stable coronary artery disease in 2013. Topical aspects of
      etiology, pathogenesis, clinical course, diagnosis, and treatment of
      microvascular angina are discussed in this review.

PMID- 30299019
TI  - [Modern approaches to the problem of hypertrophic cardiomyopathy].
AB  - This review presents modern data about a hereditary disease of myocardium -
      hypertrophic cardiomyopathy. The main features of its epidemiology,
      pathophysiological changes in intracardiac hemodynamics, formation of main
      clinical symptoms of the disease and variants of its clinical course are
      considered in terms of modern concepts. Much attention is given to
      characteristics of the variants of the disease and understanding of the formation
      of its clinical picture of each of them for the choice of the strategy for the
      management of these patients.

PMID- 30299021
TI  - Clinical use of Basophil Activation Test (BAT) in drug, food and hymenoptera
      venom allergies.
AB  - The basophil activation is emerging as a reliable and robust in vitro biomarker
      of in vivo allergy reactions. Basophil Activation Test (BAT), intended as in
      vitro stimulation of patient blood basophil with allergens, followed by flow
      cytometric detection and quantification of such activation, is nowadays a well
      established assay in a growing number of routine diagnostic labs. The
      advancements in the standardization of BAT testing and first convincing clinical
      evidence are behind this spreading of the assay in clinical lab. BAT is
      essentially an assay with superior specificity compared to any other allergy
      testing and, if appropriately used, it can have a valuable clinical utility in
      different field of allergy diagnosis. In drug allergy, very few testing
      opportunity are available for the numbers of drugs actually in the market.
      Antibiotics and analgesics are just two of the categories of drugs were BAT
      testing can have an added value for the limited specificity of IgE testing or
      limited availability of other lab testing. In food allergy, BAT is emerging as
      the more accurate assay to predict an in vivo reaction to food, helping in the
      discrimination of patients that are only sensitized versus the patient really
      allergic to an allergen. Furthermore BAT testing determining the basophil
      sensitivity can be useful for monitoring the natural resolution of allergies and
      clinical responses to immunomodulatory treatment for food allergies. For this
      characteristic, BAT has the potential to reduce the need of Oral Food Challenge
      (OFC). In the hymenoptera venom allergy, BAT is an effective tool in identifying
      primary sensitizing antigen and in the follow up of patient in venom
      immunotherapy. With this review, we want to present current state of BAT testing
      focusing on the clinical laboratory parameters and issue of this assay. A
      highlight on the standardization needs of BAT is provided, together with
      considerations on further developments and clinical evidences still to be
      achieved.

PMID- 30299020
TI  - [Emotional and personality features of patients with irritable bowel syndrome and
      bowel inflammatory diseases].
AB  - Objective: To conduct a comparative analysis of the emotional and personality
      characteristics of patients with irritable bowel syndrome (IBS) and inflammatory
      bowel disease (IBD) in remission with IBS-like symptoms. Patients and methods:
      This study carried out based at a specialized gastroenterology clinic in the
      period from 2010 to 2015 included 125 patients with IBS (IBS-D - 46, IBS-C - 20,
      IBS-M - 59) and 37 patients with IBD in remission: Crohn's disease (CD) - 11 and
      ulcerative colitis (UC) -26 patients. The levels of depression (Beck
      questionnaire), urgent and personal anxiety (Spielberger questionnaire), the
      degree of alexithymia (Toronto scale) as well as the severity of psychopathology
      and behavioral symptoms (PBS) were estimated. Results: Patients with IBS were not
      significantly different from those with IBD in remission with IBS-like symptoms
      in terms of depression, actual anxiety, alexithymia and PBS. Only the index of
      personal anxiety was significantly higher in the group of patients with IBS
      compared with IBD in remission with IBS-like symptoms (p = 0.0376). Men with IBS
      exhibited significantly higher actual anxiety than men with IBD (p = 0.04).
      Maximum severity of depression, anxiety and alexithymia was documented in the
      locking version of IBS (IBS-C) in comparison with other variants of IBS (p
      <0.05). Patients with CD in remission are characterized by higher rates of
      depression and alexithymia compared to UC (p <0.05). Behavioural disorders are
      most pronounced in the diarrheal variant of IBS and CD. Conclusion: A higher
      personal anxiety was observed in patients with IBS compared to those in remission
      of IBD with IBS-like symptoms although other parameters were not significantly
      different. Patients with IBS-C were characterized by more pronounced
      manifestations of emotional and personality disorders. More severe emotional and
      behavioral disorders distinguish CD from UC.

PMID- 30299022
TI  - Meeting nutritional needs of infants under 3 months of life within the first week
      after cardiovascular surgery.
AB  - BACKGROUND: After heart surgery requiring cardiopulmonary bypass, neonates have a
      profound metabolic response to stress. If adequate nutritional support is not
      provided this leads to loss of lean mass and deterioration of vital organs. Our
      objective was to describe the nutritional status and nutritional support achieved
      in infants younger than 3 months of life undergo in cardiovascular surgery.
      METHODS: A prospective, descriptive study was conducted in a Pediatric
      Cardiovascular intensive therapy at tertiary care center. All patients younger
      than 3 months of life admitted to the cardiovascular unit undergoing heart
      surgery between April 2013 and May2014 were included. We proposed to achieve 67
      kcal/kg/day as one of the nutritional intervention goals. The children were
      evaluated on admission and at 3 and 7 days post-surgery. RESULTS: 74 patients
      were evaluated. Total parenteral nutrition could be implemented in all patients
      that were entered into the protocol requiring parenteral nutrition. Mean volume
      administered over this period was 50 ml/kg/day (range, 25 to 80ml/kg/day).
      Evaluation on admission, at 72 hours, and one week postoperatively showed that
      70%, 69%, and 62.7%of the patients, respectively, were not able to achieve the 67
      kcal/kg/day proposed as one of the nutritional intervention goals. It was found
      that at the three study time points enteral and parental caloric intake could
      cover 100% of the metabolic resting energy expenditure (REE) estimated using the
      Schofield and WHO equations with no significant differences between both.
      CONCLUSIONS: Although the calorie intake proposed by our intervention was not
      achieved, it did cover 100% of the REE calculated by the equations.

PMID- 30299023
TI  - Respiratory syncytial virus infection in cardiac patients: outcomes preordained
      by il-6 gene polymorphism?

PMID- 30299024
TI  - Impact of dance therapy on children with specific learning disability: a two arm
      cluster randomized control study on Italian sample.
AB  - BACKGROUND: Dance Therapy can improve the quality of life for a person with
      several conditions, especially psychological wellbeing and quality of life, in
      the short and longterm. The aim of the study was to examine the effects of the
      Dance Therapy (DT) on specific learning disability (SLD) children. We wanted to
      test the impact on cognitive and emotional patterns on children with learning
      disorders. METHODS: A two arm cluster randomized control study was applied
      comparing 2 groups of SLD children (treated vs non treated). All children have
      been measured applying psychological battery before and at the end of the
      experimental protocol. RESULTS: Our data revealed significant differences between
      groups for auditory and visual recognition, for interpersonal relationships and
      for emotions recognition. DT seemed to provide positive evidence as an
      educational intervention for children with SLDs. CONCLUSIONS: Our results
      confirmed that DT protocol was an effective way to improve selfesteem, attention
      and concentration and emotional recognition in SLD children.

PMID- 30299025
TI  - Increased parental perception of sleep disordered breathing in a cohort of
      infants with ALTE/BRUE events.
AB  - BACKGROUND: An apparent life-threatening event (ALTE) describes an acute,
      unexpected change in an infant's breathing, aspect, or behavior frightening to
      the parent or caretaker. According to the new recent terminology, clinicians
      should use the term Brief Resolved Unexplained Event (BRUE) to describe an event
      occurring in an infant <1 year of age when the observer reports a sudden, brief,
      and now resolved episode. The aims of the present study in infants were: to
      investigate sleep disturbances in both ALTE event and after their classification
      according the new BRUE criteria. METHODS: We enrolled (from April to May 2016) 32
      consecutive infants referred to our ambulatory for sleep disorders for follow-up
      after an ALTE episode and 32 pair healthy controls. We administered to parents
      the adapted questionnaire "Sleep Disturbance Scale for Children - SDSC". RESULTS:
      Among enrolled infants with ALTE, there were 26 infants in line with the new BRUE
      definition, of which 10 at low risk and 16 at the high-risk event. CONCLUSIONS:
      BRUE had more referred-by-parents' sleep symptoms than controls. In particular,
      sleep disordered breathing wa prevalent in both, requiring a longer follow-up for
      this disturbance.

PMID- 30299026
TI  - The numerical value of fluid balance to predict survival in neonates requiring
      extracorporeal membrane oxygenation.
AB  - BACKGROUND: To understand numerical variation of fluid balance in neonates
      requiring Extracorporeal membrane oxygenation (ECMO) and to assess the
      relationship between hourly fluid balance and mortality. METHODS: This is a
      prospective cohort study. All neonates supported by ECMO were enrolled from
      October 2011 to September 2017. All of the enrolled neonates were divided into
      survival group and non- survival group. The numerical value of fluid balance of
      the enrolled neonates were recorded at 6h, 12h, 24h, 36h and 48h after initiation
      of ECMO respectively. The differences between the two groups were compared. The
      numerical value of fluid balance predict survival by the receiver operating
      characteristic (ROC) curve. RESULTS: Forty- eight neonates were enrolled, in
      which 35 cases were survival and the survival rate was 72.9%. The numerical value
      of fluid balance in the survival group were lower than that in the non-survival
      group at 6h, 12h, 24h, 36h and 48h after ECMO(all P < 0.05). The area under ROC
      curve at 6h, 12h, 24h, 36h and 48h after initiation of ECMO was 0.835, 0.900,
      0.839, 0.909 and 0.974 respectively. There were statistically significant in the
      numerical value of fluid balance predicting survival (all P < 0.05) and a high
      sensitivity, specificity and positive predictive value at the each time point.
      CONCLUSIONS: The negative hourly fluid balance were associated with decreased
      mortality, and the lower the numerical value of fluid balance in neonates
      requiring ECMO, the higher the survival rate.

PMID- 30299027
TI  - A study on the effect of joint detection of biochemical markers and
      electrophysiological examination in the early diagnosis of children with Green
      Barre syndrome.
AB  - BACKGROUND: To investigate the effect of early diagnosis in children with
      GreenBarre syndrome (GBS) via joint detection of biochemical markers and
      electrophysiological examination. METHODS: A total of 90 children with (GBS
      collected from the Department of Neurology, intensive care unit (ICU),
      Rehabilitation Department of Cerebral Palsy of Children's Hospital Affiliated to
      Zhengzhou University, Department of Pediatrics of First Affiliated Hospital of
      Zhengzhou University and Henan Province People's Hospital were selected as the
      research objects. According to their onset time, they were divided into group A
      (n=30) hospitalized within 3 days of onset, group B (n=30) hospitalized from 4 to
      7 days of onset, and group C (n=30) hospitalized after more than 7 days of onset.
      The titer levels of serum antiganglioside immunoglobulin G (IgG) antibodies, the
      motor nerve conduction velocity (MCV), Hoffmann reflex (Hreflex) condition and
      serum immunoglobulin in all groups of children were compared. RESULTS: The levels
      of serum antiganglioside IgG antibodies in three groups of children from low to
      high were group A < group B < group C. MCV decreasing rates in group A, B and C
      were successively 3.33%, 16.66% and 29.99%, namely group A < group B < group C.
      60 cases of H reflex were detected in each group, and the abnormal rates were
      successively 76.66%, 81.66% and 95% respectively in group A, group B and group C,
      namely group A < group B < group C. The serum levels of immunoglobulin in three
      groups of children from low to high were group A < group B < group C (p<0.05).
      CONCLUSIONS: Anti-ganglioside antibody, electrophysiological parameter and serum
      level of immunoglobulin can be helpful in the diagnosis of GBS, and the changes
      in them can be monitored clinically so as to carry out the early treatment
      effectively for children and improve the prognosis.

PMID- 30299028
TI  - New medical device coating mouth gel for temporary relief of teething symptoms: a
      pilot randomised, open-label, controlled study.
AB  - BACKGROUND: This study verified the feasibility of the monthly recruitment rate,
      tested the Face, Legs, Activity, Cry and Consolability Pain Assessment Tool
      (FLACC) for pain in infants and collected preliminary efficacy and safety data of
      a new proprietary oral gel formulation of high-molecularweight hyaluronan (HMWHA)
      for the relief of teething. Results will support the design a future main trial
      vs local anaesthetic, that is currently the only clinically proven pain reliever.
      METHODS: This was a pilot, randomised, controlled, multicentre, open-label,
      parallel-group trial. It was performed in two Romanian clinics recruiting infants
      from 3 to 36 months. Teething diagnosis was based on a minimum of three symptoms
      such as: local pain, swelling, erythema, hyper salivation and depth
      characteristics of unerupted tooth. Absence of subcutaneous mucosal laceration
      was also required. The children were assigned either to HMWHA (HABPX V 3.3,
      Bioplax Ltd, UK), or to standard drug (Dentinox(r)-Gel N) and treated for 7
      consecutive days. Investigators recorded the primary endpoints: swelling, redness
      and pain (by FLACC method), on days 0, 3 and 7. Changes in crying, mouth spasms,
      salivation, local pain, swelling, and redness were the secondary endpoints,
      recorded daily by the parents, on diary cards. Tolerability was assessed on day
      14, too. RESULTS: 27 Infants were allocated in HMWHA, and 30 in standard drug.
      Enrolment rate was 9 patients/month/site. A significant reduction for HMWHA group
      was evidenced in pain, swelling (from day 0 to 7, p = 0.034 between groups),
      redness (from day 0 to 3, p = 0.045 and from day 0 to 7, p < 0.001 between
      groups) and confirmed by the parents' diary records. Pain measurements obtained
      by FLACC method are consistent with the data belonging to other parameters.
      Investigator's global assessment of performance was in favour of the HMWHA (p <
      0.005). Only two patients, both belonging to standard drug group, experienced
      adverse events (fever, not related to treatment) and dropped out of the study.
      CONCLUSIONS: The results solve the feasibility questions and clearly evidence the
      performance of HABPX V 3.3 in teething symptoms, exceeding the objectives of a
      simple pilot trial to some extent. Coating oral gels containing HMWHA could be a
      therapeutic solution for both parents and physicians in managing the irritation
      and pain resulting from tooth eruption in children.

PMID- 30299029
TI  - Lifestyle factors among adolescent.

PMID- 30299030
TI  - Helicobacter pylori infection in children with portal hypertensive gastropathy: a
      clear indication for clinical practice.

PMID- 30299031
TI  - Outcomes of infants born near term: not quite ready for the "big wide world"?
AB  - Until recently, there has been a strongly held belief on the part of neonatal and
      paediatric clinicians that outcomes for infants born close to term are not
      different from those of babies born at full term. In the last decade, however,
      this assumption has been challenged by reports suggesting that this is not
      correct, and highlighting differences in morbidity and mortality both in the
      short and long term. This has led to development of new terminology to more
      accurately reflect the impact of immaturity associated with birth at 32-33 weeks
      (moderately preterm) and 34-36 weeks (late preterm) of gestation. These babies
      account for around 5-7% of all births and more than 75% of the preterm births in
      developed countries, so this new recognition of the associated increase in
      adverse outcomes may have a substantial impact on health care services. This
      review article will discuss the changing perceptions and concepts of gestational
      age in the preterm population, and explore the recent and emerging evidence
      around neonatal, early childhood, school-age, adolescent and adult outcomes for
      babies who are born moderately preterm and late preterm. It highlights important
      neonatal and childhood morbidities, and will summarise associated health care,
      developmental and educational problems of affected children. The implications for
      the provision of ongoing primary and secondary health care, educational and
      social support to this large and heterogeneous Group of individuals will be
      discussed.

PMID- 30299032
TI  - [Exacerbation of chronic obstructive pulmonary disease: the role of the molecular
      genetic method for the identification of pathogenic agents].
AB  - The study dealt with etiological diagnostics of bacterial exacerbations of
      chronic obstructive pulmonary disease (COPD). Samples of bronchial secretion were
      obtained from 73 patients hospitalized in connection with COPD exacerbations and
      investigated by the culture method and PSR. The former technique revealed
      bacterial pathogens in 64 (82%) patients. Gram-positive bacteria (Streptococcus
      pneumoniae) predominated in patients with stage I and II COPD, Gram-negative
      (Pseudomonas aeruginosa) and mixt infection in those with stage III and IV COPD.
      CPR proved more sensitive for isolation of DNA of Gram-negative pathogens
      (Haemophilus influenzae and Enterobacteriaceae).

PMID- 30299034
TI  - Oral Pathology Quiz #92. Case number 1.

PMID- 30299035
TI  - [Morphology, Ecology, and 18S rRNA Phylogeny of the Green Microalgal Order
      Protosiphonales (Chlorophyceae, Chlorophyta)].
AB  - The system of the green microalgal order Protosiphonales (Chlorophyceae,
      Chlorophyta) constructedbased on morphological, ecological, and molecular genetic
      data is considered. Subdivision of theorder (=macroclade Stephanosphaerinia) into
      four groups is proposed, with three probably corresponding tothe families
      Stephanosphaeraceae, Chlorococcaceae, and Protosiphonaceae and the fourth having
      an indefinitestatus. The diagnostic characteristics of the families, genera, and
      species are discussed, as well as the independentrank of some taxa. Morphological
      descriptions of a number of species are supplemented. Based onpolyphasic
      approach, strain ACSSI 23 is proposed as a candidate for a new genus and species.

PMID- 30299033
TI  - [A case of rare inhibitory coagulopathy - acquired hemophilia A].
AB  - Inhibitory coagulopathy is a rare variant of hemorrhagic syndrome. Acquired
      hemophilia A is caused by the formation of inhibitors (antibodies) to Factor VIII
      of the blood coagulation system leading to impaired activation of the key stage
      of blood clotting (factor X) and development of hemorrhagic syndrome of different
      severity. Acquired hemophilia A is a rare disease with an incidence of 1.38-1.48
      per 1 million population per year. We report a case off severe idiopathic
      acquired hemophilia A in a 53 year-old woman manifest as skin hemorrhages,
      subcutaneous and intramuscular hematomas. Hemostatic therapy described in the
      article resulted in the elimination of hemorrhagic syndrome and complete
      remission. This case represents a rare disease the knowledge of which can be
      useful for preventing the development of debilitating complications, and
      sometimes saving the patient's life.

PMID- 30299036
TI  - Oral Pathology Quiz #92. Case number 2.

PMID- 30299037
TI  - Oral Pathology Quiz #92. Case number 4.

PMID- 30299038
TI  - Oral Pathology Quiz #92. Case number 3.

PMID- 30299039
TI  - Oral Pathology Quiz #93. Case number 1.

PMID- 30299041
TI  - Oral Pathology Quiz #93. Case number 3.

PMID- 30299040
TI  - Oral Pathology Quiz #93. Case number 2.

PMID- 30299042
TI  - Optimal settings for childbirth.
AB  - Many studies highlight how health is influenced by the settings in which people
      live, work, and receive health care. In particular, the setting in which
      childbirth takes place is highly influential. The physiological processes of
      women's labor and birth are enhanced in optimal ("salutogenic," or health
      promoting) environments. Settings can also make a difference in the way maternity
      staff practice. This paper focuses on how positive examples of Italian birth
      places incorporate principles of healthy settings. The "Margherita" Birth Center
      in Florence and the Maternity Home "Il Nido" in Bologna were purposively selected
      as cases where the physical-environmental setting seemed to reflect an embedded
      model of care that promotes health in the context of childbirth. Narrative
      accounts of the project design were collected from lead professional and direct
      inspections performed to elicit the key salutogenic components of the physical
      layout. Comparisons between cases with a standard hospital labor ward layout were
      performed. Cross-case similarities emerged. The physical characteristics mostly
      related to optimal settings were a result of collaborative design decisions with
      stakeholders and users, and the resulting local intention to maximize safe
      physiological birth, psychosocial wellbeing, facilitate movement and relaxation,
      prioritize space for privacy, intimacy, and favor human contact and
      relationships. The key elements identified in this paper have the potential to
      inform further investigations for the design or renovation of all birth places
      (including hospitals) in order to optimize the salutogenic component of any
      setting in any country.

PMID- 30299043
TI  - [LISHUTA EXTRANODAL INVOLVEMENT OF THE HEART IN LYMPHOMAS: A CLINICAL CASE OF
      LARGE B-CELL LYMPHOMA AND LITERATURE REVIEW].
AB  - The authors report a case of rare cardiac involvement in lymphoma, one of the
      manifestations of which was rhythm and conduction disorders with their resolution
      after chemotherapy. Also presented are clinical manifestations of heart lesions
      in lymphoma and modern methods of their diagnostics and treatment.

PMID- 30299044
TI  - Oral Pathology Quiz #93. Case number 4.

PMID- 30299046
TI  - Oral Pathology Quiz #91. Case number 1.

PMID- 30299045
TI  - [Efficient treatment of chronic respiratory failure associated with morbid
      obesity].
AB  - Severe obesity sometimes leads to chronic respiratory failure. This condition is
      termed obesity-hypoventilation or Pickwickian syndrome. This article reports
      clinical observation illustrating effectiveness of noninvasive pressure support
      ventilation for the treatment of hypercapnic respiratory failure in a patient
      with morbid obesity. The treatment strategies for such patients are discussed.

PMID- 30299047
TI  - [Production of Antimicrobial Polypeptides by Propionibacterium freudenreichii RVS
      4-irf].
AB  - Propionibacterium freudenreichii RVS-4-irf is a probiotic bacterium producing
      antimicrobialexometabolites applicable for foodstuff protection. Production of
      antimicrobial factors other than lowmolecularpropionates was observed in media
      with and without trypton. A method was developed for productionof the fraction of
      high-molecular mass exopolymers from the culture liquid. Their polypeptide nature
      wasconfirmed using proteinase K. The preparation of extracellular polypeptides
      from P. freudenreichii RVS-4-irfexhibited species-specific activity in
      suppression of fungal and bacterial growth.

PMID- 30299048
TI  - Oral Pathology Quiz #91. Case number 2.

PMID- 30299049
TI  - [A rare combination of systemic scleroderma, sarcoidosis and psoriasis at
      advanced age].
AB  - We report a rare combination of systemic sclerosis, sarcoidosis, psoriatic
      arthritis and diverticulosis with severe complications in a 41-year-old male who
      has been treated by a rheumatologist since 10 years of age.

PMID- 30299050
TI  - Oral Pathology Quiz #91. Case number 3.

PMID- 30299051
TI  - Oral Pathology Quiz #91. Case number 4.

PMID- 30299052
TI  - [Secondary Metabolites of Fungi of the Usti Section, Genus Aspergillus and Their
      Application in Chemosystematics].
AB  - Secondary metabolites of 22 fungal strains (genus Aspergillus, section Usti)
      isolated at diverse geographicregions, including the Arctic permafrost deposits,
      were studied. The studied strains were found tosynthesize a variety of
      biologically active compounds, structurally identified as drimane
      sesqueterpenoids,isoquinoline alkaloids (TMC-120 A-C, derivative 1),
      meroterpenoids (austalides O and J), and anthraquinonepigments (averufin,
      versicolorin C). Desferritriacetylfusigen production by A. calidoustus isolates
      isreported for the first time. The individual spectra of secondary metabolites
      were used for reidentification of17 strains, of which 15 were identified as A.
      calidoustus and two, as A. pseudodeflectus.

PMID- 30299054
TI  - [Debatable aspects of pathogenesis and diagnostics of irritable bowel syndrome
      (IBS) and inflammatory bowel diseases with IBS-like diseases].
AB  - Aim of review: To analyze current publications devoted to controversial issues of
      pathogenesis, diagnosis and differential diagnosis of irritable bowel syndrome
      (IBS) and inflammatory bowel disease (IBD) in remission with IBS-like symptoms.
      Key points: There are three main hypotheses discussed in the literature: 1) IBS
      as a prodrome, pre-stage of the IBD; 2) IBS and IBD are different variants of
      inflammatory disorder which is common to both diseases; 3) The onset of IBS-like
      symptoms in IBD patients in remission. Conclusion: It is shown that modern
      literature data on this issue is contradictory and ambiguous.

PMID- 30299055
TI  - [Effect of Selenium-Containing Biocomposites Based on Ganoderma Mushroom Isolates
      Grown in the Presence of Oxopropyl-4-Hydroxycoumarins, on Bacterial
      Phytopathogens].
AB  - Effect of selenium-containing biocomposites obtained from submerged cultures of
      macrobasidiomycetesGanoderma applantum, G. cattienensis, G. colossus G. lucidum,
      G. neojaponicum, and G. valesiacum,on plant pathogenic bacteria Clavibacter
      michiganensis ssp. sepedonicus (Cms), Micrococcus luteus,
      Pectobacteriumatrosepticum, Pectobacterium carotovorum subsp. carotovorum,
      Pseudomonas fluorescens, Pseudomonasviridiflava, and Xanthomonas campestris was
      studied. Oxopropyl-4-hydroxychromenones were used as componentsof the fungal
      nutrient media. The bacteriostatic and bactericidal activity of the Se-containing
      and Sefreesubstances of fungal origin against plant pathogenic bacteria was
      determined using colony-forming unitscount, the agar well diffusion method, and
      by turbidity measurements of bacterial suspensions. The compositesproduced from
      the extracellular metabolites of G. cattienensis SIE1302 with 4-hydroxy-3-(3-oxo
      1,3-diphenyl propyl)-chromen-2-one (S(45)), and of G. lucidum SIE1303 with 4
      hydroxy-3-(3-oxo-1-(3-nitrophenyl)-3-phenylpropyl)-chromen-2-one (S(NO2))
      possessed the most pronounced antibacterial actionagainst Cms. The composites
      produced from the isolates of G. valesiacum 120702 with S(NO2) showed themaximal
      antibacterial activity against Xanthomonas campestris B-610. High antimicrobial
      effect of G. lucidum1315 with S(NO2) against Xanthomonas campestris B-610 and of
      G. colossus SIE1301 against Pseudomonas fluorescensEL-2.1 was revealed. The
      pioneering information on the biological activity of coumarin series compoundsin
      their application for producing the substances of fungal origin was obtained.

PMID- 30299056
TI  - [Topical problems of chronic gastritis].
AB  - The authors propose the definition of chronic gastritis with a brief overview of
      the history of investigation of this diseases and its prevalence with special
      reference to (1) the bacterial profile and its role in the development of
      infectious and inflammatory process in gastric mucosa, (2) the modern state of
      and new trends in the classification of chronic gastritis including their
      advantages and disadvantages, (3) the relationship between chronic gastritis and
      functional gastroduodenal dyspepsia syndrome. It is concluded that mucous
      microflora plays an important factor in the development ofpathology but H.pylori
      is not its predominant component. Modern classifications of chronic gastritis
      provide a basis for a deeper insight into evolution of chronic gastritis and its
      transformation into cancer. The diagnosis of 'chronic gastritis with functional
      gastroduodenal dyspepsia syndrome' is invalid.

PMID- 30299057
TI  - [Formation of Ag/AgCl Nanoparticles in the Matrix of the Exopolysaccharide of a
      Diazotrophic Strain Azotobacter chroococcum XU1].
AB  - A complex of Ag/AgCl nanoparticles was synthesized on the basis of the
      extracellular polysaccharide of Azotobacter chroococcum XU1 and 10 mM AgNO3
      solution. The complex was characterized by UV spectroscopy, X-ray diffraction,
      and scanning electron microscopy. Colloidal solutions of the complex had
      absorption peaks at 260 and 420 nm, indicating the formation Ag/AgCl
      nanoparticles. The size of the nanoparticles varied from 6 to 50 nm. The
      nanobiocomposite consisting of the exopolysaccharide matrix and Ag/AgCl
      nanoparticles exhibited a fungicidal effect against such plant pathogens as
      Fusarium oxysporum f. sp. vasinfectum and Verticillium dahliae.

PMID- 30299058
TI  - [Extragastric symptoms associated with Helicobacter pylori infection].
AB  - This review article highlights the modern views of manifestations associated with
      Hp infection. The data are presented about the negative impact of the infection
      on the state of the musculoskeletal system, the development of migraine,
      progression of diffuse liver disease and the risk of developing liver cancer. The
      paper also provides information on the possible effects of Helicobacter pylori
      infection on the formation of halitosis, tympanosclerosis, male reproductive
      health disorders, colorectal cancer, Alzheimer's and Parkinson's disease, pre
      eclampsia during pregnancy, and idiopathic chronic urticaria. In addition, the
      negative relationship between Hp infection, bronchial asthma, and inflammatory
      bowel disease is considered.

PMID- 30299059
TI  - [Criteria for granting permission for disabled persons to participate in the
      Ready for Labor and Defense training program].
AB  - Rehabilitation, adaptation, and social integration of the disabled are the
      priority issues of social welfare policy in the Russian Federation. This includes
      the enhancement of availability ofphysical education and adapted sports programs.
      One of the best practices for the improvement ofphysical activity among the
      population is the "Ready for labour and defense" training system (GTO). However,
      it is not adapted for those with physical challenges and disabilities. To involve
      this special fraction of the population in physical activity and participation in
      the GTO system, disability groups eligible for this activity need to be
      identified. They can include individuals with visual (VI), intellectual (II),
      hearing (HI), and locomotor problems as well as those with transplanted organs
      (TO). Also, minimum disability criteria (MDC) for the participants from each
      group which would make them eligible to practice an adapted GTO system should be
      defined. The development of MDC for individuals with VI, II, HI, and TO is
      relatively easy as they are common for most adapted sports. However, it remains a
      challenge for persons with locomotor problems since they make up a very diverse
      group bearing in mind that the rules of the International Paralympic Committee
      envisage different MDC for different adapted sports. There are two possible
      solutions: (1) to develop specialized MDC for each sport discipline included in
      the GTO system, (2) to develop universal MDC for all disciplines. The next step
      in promoting the GTO system among individuals with physical challenges and
      disabilities will be the development of the para- GTO program that would be
      unique and adapted for all categories of the disabled individuals.

PMID- 30299060
TI  - [Morphological, Physiological, and Biochemical Characteristics of a Benzoate
      Degrading Strain Rhodococcus opacus 1CP under Stress Conditions].
AB  - Ability of actinobacteria Rhodococcus opacus 1CP to survive under unfavorable
      conditions and retain its biodegradation activity was assessed. The morphological
      and ultrastructural features of R. opacus 1CP cells degrading benzoate in the
      presence of oxidants and stress-protecting agents were investigated. The cells of
      R. opacus 1CP were resistant to oxidative stress caused by up to 100 mM H2O2 or
      up to 25 MUM juglone (5-oxy-1,4-naphthoquinone). After 2 h of stress impact,
      changes in the fatty acid composition, increased activity of antioxidant enzymes,
      and changes in cell morphology and ultrastructure were observed. The strain
      retained its ability to degrade benzoate. Quercetin had a protective effect on
      benzoate-degrading cells of R. opacus 1CP. The strategy for cells survival under
      unfavorable conditions was formulated, which includeddecreased cell size/volume
      and formation of densely-packed cell conglomerates, in which the cells are
      embedded into a common matrix. Formation of conglomerates may probably be
      considered as a means for protecting the cells against aggressive environmental
      factors. The multicellular conglomerate structure and the matrix material impede
      the penetration of toxic substances into the conglomerates, promoting survival of
      the cells located inside.

PMID- 30299061
TI  - [Obesity and cardiovascular system].
AB  - Obesity is a serious medico-social and economic problem. Increased body mass
      index is associated with a rise in the general mortality rate and mortality due
      to cardiovascular diseases. In this article, modern views of the influence of
      obesity on the cardiovascular system are considered.

PMID- 30299063
TI  - [The Factor Stabilizing the Bioluminescence of PVA-Immobilized Photobacteria].
AB  - Immobilization of photobacteria in the cryogel of polyvinyl alcohol (PVA) was
      carried out. Immobilization was found to result in increased intensity and
      stability of bioluminescence. The elements determining the stability of
      bioluminescence were investigated. Selection of the strain was found to be of the
      highest importance. Among immobilized cells, Photobacterium phosphoreum exhibited
      the most intense and prolonged light emission, while Vibrio harveyi showed the
      least one. The technological procedures for cryogenic immobilization of
      photobacteria were determined. The role of the environment of gel formation in
      the preservation of the bioluminescence activity was determined. In the gels
      formed in rich medium for submergedcultivation of photobacteria, almost 100%
      luminescence activity was preserved, while light emission was considerably
      prolonged. Bioluminescence intensity of the preparations was shown to depend
      significantly on pH of the incubation medium. The pH shift to acidic values
      during prolonged incubation of immobilized cells was shown to be one of the
      factors of bioluminescence quenching. The stress effects of cryogenic
      immobilizationwere found to have an insignificant effect on the temperature
      profile of bioluminescence. Decreased reduction rate of the luciferase flavin
      substrate was shown to be a possible reason for bioluminescence quenching.

PMID- 30299062
TI  - [Therapeutic Monitoring Plasma Imatinib to Improve Results of the Treatment of
      Chronic Myeloleukosis].
AB  - The achievement of early cytogenetic and molecular responses is the major
      objective of therapy and a main prerequisite for the favourable long-term outcome
      of the disease. The maintenance of dose intensity and management of adverse
      events are keys to successful treatment of chronic myeloid leukemia (CML) with
      imatinib. Therapeutic monitoring and testing the drug level in blood are the
      efficient tools for the treatment of patients with CML and can be usedfor
      analysis of treatment failure or suboptimal response to therapy, suspected
      noncompliance, drug interactions or unexpected adverse reactions.

PMID- 30299064
TI  - [Early diagnosis of stress-induced hypertension in young employees of state law
      enforcement agencies].
AB  - Psychoemotional stress is one of the leading cardiovascular risk factors. The aim
      of this study was to explore manifestations of arterial hypertension (AH) in
      young men employed in the stress associatedfield works. Material and methods. A
      total of 68 young men, exposed to job stress (JS) of different severity during 1
      to 5 years were surveyed. The control group was formed of persons whose daily
      work was unrelated to operational activities. The study included ambulatory
      monitoring (AM) blood pressure (BP) on different days of the week, comparing the
      results of the office and DMBP determination and assessment of resistance to a
      variety of diagnostic loads. Results. The study revealed an increase of AMBP
      indicators during the working day and their normalization at weekend. The
      comparison of the results of office and ambulatory determination of BP
      demonstrated that different forms of stressful AH (stable, isolated office and
      latent) occurred significantly more often than in the control group. These
      changes almost completely disappeared at weekends. The tolerance
      ofpsychoemotional testing was much worse than that of traditional exercises. It
      is proposed to more extensively use AMBP during regular medical examinations of
      young men exposed to JS in order to establish a timely differential diagnosis of
      various forms of stressful hypertension.

PMID- 30299066
TI  - [Model of the Regulation of Activity of Immobilized Enzymes (Amylases) in Soil].
AB  - The preservation of activity of extracellular enzymes in soil is presently
      associated with their immobilization on organic or inorganic carriers. Enzyme
      immobilization results, however, in a significant decrease in enzymatic activity.
      In the present work, the mechanism responsible for promotion of the catalytic
      activity was revealed, as well as the favorable effect of low-molecular
      alkylhydrozybenzenes of the class of alkylresorcinols, which are common in soil
      organic matter, on stability of immobilized enzymes (exemplified by amylases) by
      their post-translational modification. Optimal conditions (enzyme to sorbent
      ratio, pH optimum, CaCl2 concentration, and sorption time) for amylase sorption
      on a biological sorbent (yeast cell walls) were determined and decreased activity
      of the immobilized enzyme compared to its dissolved state was confirmed.
      Alkylresorcinols (C7AHB) at concentrations of 1.6 to 80 mM were found to cause an
      increase of amylase activity both in the case of already sorbed enzymes (by 30%)
      and in the case of a free dissolved enzyme with its subsequent immobilization (by
      50-60%). In both cases, the optimal C7AHB concentration was16 mM. Amylase
      stability was determined for C7AHB-modified and unmodified enzymes immobilized on
      the biological sorbent after two cycles of freezing (-20 degrees C) and thawing
      (4 degrees C). Inverse dependence was revealed between increasing stability of
      C7AHB-modified enzymes and an increase in their activity, as well as higher
      stability of immobilized modified amylases than of the dissolved modified enzyme.
      Investigation of the effect of C7HOB-modification in the preservation of activity
      in immobilized amylases after four freeze-thaw cycles revealed: (1) better
      preservation of activity by the modified immobilized enzymes compared to
      immobilized ones; (2) differences in the dynamics of activity loss within
      compared pairs, with activity ofimmobilized amylases decreasing after the second
      cycle to a lower level (42%) than activity of the modified immobilized enzymes
      after the fourth cycle (48%). These results demonstrate that in the preservation
      of activity of extracellular enzymes in soil both stabilization mechanisms are of
      importance: immobilization on organic carriers and modification of the enzyme
      conformation by low-molecular compounds with the functions of chemical
      chaperones.

PMID- 30299065
TI  - [Prevalence and typological characteristics of atherosclerotic lesions in carotid
      arteries associated with metabolic syndrome as revealed by multislice computed
      tomography].
AB  - Aim: To study the character, prevalence, and typological structure of
      atherosclerotic changes in major arteries by multislice computed tomography in
      patients with various metabolic disorders. Material and Methods: Carotid arteries
      of 78 patients with metabolic syndrome or type 2 diabetes mellitus and without
      carbohydrate metabolism disorders were examined by multislice computed
      tomography. Results: The study revealed various types of atherosclerotic plaques
      differing in the composition of lipid, lipid-fibrotic and calcium components. The
      latter were especially well expressed in diabetes. Conclusion: All types of
      atherosclerotic plaques are roughly equally represented in the structure of
      atherosclerotic lesions of carotid arteries in patients with metabolic syndrome
      in the absence of type 2 diabetes. Diabetic patients had vascular lesions with
      especially high density of atherosclerotic plaques.

PMID- 30299067
TI  - [The risk of cardiovascular death in type 2 diabetes].
AB  - Aim: To evaluate effects of metabolic disorders on the risk of cardiovascular
      death in patients with type II diabetes based on Framingham risk score. We
      analyzed results of examination of 210 men and 210 women with type 2 diabetes who
      applied for medical care to the VM center of Endocrinology during 1997-2014. A
      virtual control group was formed matching real patients in terms of the number,
      sex, age, and height having ideal body mass index, total cholesterol and high
      density lipoprotein cholesterol levels. The average risk of cardiovascular death
      in patients with type 2 diabetes was equal to 4,56+/-0,254% compared with 0,6+/
      1,028% in the virtual control group. The differences was significant (p <0,001).
      The minimum risk for the patients of the two groups was estimated at 0,001% and
      0,01% respectively. The maximum risk of cardiovascular death is 34,17% in
      patients with diabetes and 8,24% in controls. It is concluded that type 2
      diabetes and related metabolic disorders significantly increase the risk of
      cardiovascular death.

PMID- 30299069
TI  - [Pathogenesis of myocarditis in patients with bronchial asthma and
      pecilomycosis].
AB  - We studied the influence of activation ofpecilomycotic infection in blood on the
      morphofunctional state of myocardium based on the clinical and pathomorphological
      data. The study included 23 patients with bronchial asthma (BA) concomitant with
      pecilomycosis after acute viral respiratory infection; protocols of autopsies and
      pathological sections of the heart muscle of the patients who died from asphixy
      and acute cardiac insufficiency were analyzed. Histological sections showed up
      vascular dystonia of the microcirculation bed, arteriole spasms, wall destruction
      in small and medium-size vessels and the adjacent muscular tissue, stromal
      oedema, valvular swelling, andperiwall endocarditis. Cardiac cavities and
      coronary vessels contained erythrocyte-rich thrombi with ferulas of Paecilomyces
      at different stages of development. Clinical manifestations of destructive
      changes in the heart muscle developing under effect of Paecilomyces infection had
      the form of rhythm and conductivity disorders. The local protective inflammatory
      reaction of productive type had the form of intermediate and vascular-type
      myocarditis passing to postmyocarditic cardiosclerosis. Periodic bursts of
      activation ofpecilomycotic infection in blood with the accumulation of fungal
      phospholipase A2 and lipid metabolites produced membranotoxic effect and can play
      the key role in the development of atherosclerosis and hypertensive disease in
      patients with BA and pecilomycosis.

PMID- 30299068
TI  - [Dynamics of clinical, X-ray and functional data during treatment of patients
      with sarcoidosis].
AB  - Aim: To analyze the literature data and the results of original studies on the
      respiratory function in patients with sarcoidosis. Material and methods: The
      study included 1199 patients with sarcoidosis (67.8% women and 32.2% of males,
      median age 43 years). The first X-ray stage was documented in 34.8% of patients ,
      stage II in 57.0%, stage III in 6.1%, stage IV in 1.3%, stage 0 in 0.7%. One
      patient (0.1%) had pleural sarcoidosis. Loefgren syndrome was diagnosed in 20% of
      the patients. In 658 patients (54.9%) the diagnosis was confirmed by biopsy
      studies. Results: The patients with sarcoidosis exhibited significant correlation
      between radiographic and spirometric characteristics. In those with Loefgren
      syndrome, all breathing parameters were much better than in the remaining ones.
      Changes of spirometry parameters were more pronounced in smokers and in patients
      with concomitant lung diseases. However, the lung function remained impaired
      after adjustment for these factors, and 9,7% of the cases positively responded to
      the administration of a short-acting bronchodilator. X-ray examination and
      spirometry are independent methods for the evaluation of the health status of
      patients with sarcoidosis and their results do not always correlate with each
      other after different treatment regimens. Changes in X-ray image and lung vital
      capacity were consistent in patients treated with prednisone, methotrexate and
      pentoxifylline, but not in the cases treated with vitamin E and in the absence of
      treatment. Spirometry with simultaneous X-ray examination is recommended for all
      patients with intrathoracic sarcoidosis. Conclusion: Forced vital capacity of
      lungs (FVC) is an independent criterion for evaluating the condition of patients
      with sarcoidosis and the effectiveness of the treatment.

PMID- 30299070
TI  - [Medical scores in clinical practice. Part III. Heart Failure].
AB  - Scores for heartfailure prognosis are discussed in the review. The prognostic
      scores may help in patients' selection for advanced device-based treatment.

PMID- 30299071
TI  - ["HELICARB" - the first Russian breath test kit with 99 % C-urea for Helicobacter
      pylori: from idea to registration].
AB  - The present study was aimed to develop and introduce in medical practice the
      first Russian kit for the C-urea breath test of Helicobacter pylori. The newly
      created kit was given the commercial name "HELICARB" and successfully passed
      technical, toxicological, clinical, and laboratory testing. The optimal dose of
      13C-urea was determined and various devices needed to perform the test were
      compared. The results were approved by the Federal Service for Supervision in the
      health sector Roszdravnadzor) that issued the Registration certificate No RZN
      2016/3773 (order No 1641 of 02.29.2016), which gives the right to manufacture and
      use the "HELICARB" test kit at the territory of the Russian Federation.

PMID- 30299072
TI  - [A critical incident during marathon competition as a result of metabolic
      decompensation].
AB  - A case of polyorganic insufficiency syndrome associated with coma, convulsive
      disorder, acute hepato-renal and respiratory dysfunction, hypovolemic shock, and
      hyperthermal syndrome in a 46 year-old participant ofa marathon competition is
      reported. The clinical picture was dominated by acute hepatic insufficiency
      treated with remaxol to activate substrate phosphorylation under effect of
      exogenous succinate for slowing down the development of energy deficit in
      mitochondria under condition of oxygen deficit. This case can be regarded as a
      variant of correction of mitochondrial dysfunction with the use of a mitochondria
      targeted medication such as succinate-containing remaxol. This medication reduced
      AST and ALT activities and utilization of endogenous enzymes for succinate
      synthesis from alanine and aspartate under hypoxic conditions. Prescription of
      remaxol as a form of direct substitution therapy was dictated by pathogenetic
      considerations.

PMID- 30299073
TI  - Nitrogen and Sulfur Co-Doped Graphene Nanosheets to Improve Anode Materials for
      Sodium-Ion Batteries.
AB  - Sodium-ion batteries (SIBs) attract more attention because of sodium's abundant
      availability, affordable price, and potential to be an effective anode material.
      Meanwhile, carbon-based materials provide the most promising anode materials.
      Because of the large radius of sodium ions, SIBs do not exhibit favorable
      electrochemical performance. Introducing heteroatoms into the carbon-lattice is
      an effective strategy to enlarge the interlayer space of carbon-based materials
      which can improve carbon's electrochemical performance. In addition, anode
      materials with a surface-induced capacitive process can enhance the SIB's
      electrochemical performance because its capacitive process increases the kinetics
      of ion diffusion. Here, we describe an SIB's anode material containing nitrogen
      and sulfur co-doped graphene sheets [denoted as poly(2,5-dimercapto-1,3,4
      thiadiazole) (PDMcT)/reduced graphene oxide (RGO)] which are synthesized via
      carbonization of PDMcT polymerized on the surface of GO. PDMcT/RGO exhibited high
      capacities (240 mA h g-1 at 500 mA g-1), improved rate performance (144 mA h g-1
      at 10 A g-1), and good cycling stability (153 mA h g-1 after 5000 cycles at 5000
      mA g-1). These unique results are attributed to the enlarged interlayer spacing
      and electronic conductivity from the heteroatoms which facilitate the sodium
      ion's insertion and electron transport. These results represent that PDMcT/RGO is
      a great potential anode material for SIBs.

PMID- 30299074
TI  - Effect of Carboxylic Acid-Doped Carbon Nanotube Catalyst on the Performance of
      Aqueous Organic Redox Flow Battery Using the Modified Alloxazine and Ferrocyanide
      Redox Couple.
AB  - Alloxazine and ferrocyanide are suggested as the redox couple for an aqueous
      organic redox flow battery (AORFB). Alloxazine is further modified by carboxylic
      acid (COOH) groups (alloxazine-COOH) to increase the aqueous solubility and to
      pursue a desirable shift in the redox potential. For obtaining a better AORFB
      performance, the overall redox reactivity of AORFB should be improved by the
      enhancement of the rate-determining reaction of the redox couple. A carboxylic
      acid-doped carbon nanotube (CA-CNT) catalyst is considered for increasing the
      reactivity. The utilization of CA-CNT allows for the induction of a better redox
      reactivity of alloxazine-COOH because of the role of COOH within alloxazine-COOH
      as a proton donor, the fortified hydrophilic attribute of alloxazine-COOH, and
      the increased number of active sites. With the assistance of these attributes,
      the mass transfer of aqueous alloxazine-COOH molecules can be promoted. However,
      CA-CNT does not have an effect on the increase of the redox reactivity of
      ferrocyanide because the redox reaction is not affected by the same influence of
      protons that the redox reactivity of alloxazine-COOH is affected by. Such a
      behavior is proven by measuring the electron transfer rate constant and
      diffusivity. With regard to AORFB full cell testing, when CA-CNT is used as a
      catalyst for the negative electrode, the performance of the AORFB increases.
      Specifically, the charge-discharge overpotential and infrared drop potential are
      improved. As a result, the voltage efficiency affected by the potentials
      increases to 64%. Furthermore, the discharging capacity reaches 26.7 A h.L-1, and
      the state of charge attains 83% even after 30 cycles.

PMID- 30299075
TI  - Nanostructured Anatase Titania as a Cathode Catalyst for Li-CO2 Batteries.
AB  - Lithium-carbon dioxide (Li-CO2) batteries have garnered significant interest over
      the past 5 years as next-generation energy storage devices. In this article, we
      report a nanocomposite of anatase titania nanoparticles (TiO2-NPs), carbon
      nanotubes, and carbon nanofibers as a freestanding gas diffusion cathode for Li
      CO2 batteries. Nanostructured anatase TiO2 is demonstrated as a low-cost, easy-to
      synthesize catalyst for CO2 capture and utilization. With the developed composite
      electrode, we confirm the successful reversibility of the carbon dioxide
      reduction reaction and evolution reaction at the cathode and demonstrate improved
      Li-CO2 cell performance through a variety of materials and electrochemical
      characterization techniques.

PMID- 30299076
TI  - The effect of a controlled release of Epinephrine hydrochloride from PLGA
      microchamber array: in vivo studies.
AB  - This paper presents the synthesis of highly biocompatible and biodegradable poly
      lactide-co-glycolide (PLGA) microchamber arrays sensitive to low-intensity
      therapeutic ultrasound (1 MHz, 1-2W, 1 min). A reliable method was elaborated
      that allowed the microchambers to be uniformly filled with epinephrine
      hydrochloride (EH), with the possibility of varying the cargo amount. The maximum
      load of EH was 4.5 MUg per array of 5 mm x 5 mm (about 24 pg of EH per single
      microchamber). A gradual, spontaneous drug release was observed to start on the
      first day, which is especially important in the treatment of acute patients.
      Ultrasound triggered a sudden substantial release of EH from the films. In vivo
      real-time studies using a laser speckle contrast imaging system demonstrated
      changes in the hemodynamic parameters as a consequence of EH release under
      ultrasound exposure. We recorded a decrease in blood flow as a vascular response
      to EH release from a PLGA microchamber array implanted subcutaneously in a mouse.
      This response was immediate and delayed (one and two days after the implantation
      of the array). The PLGA microchamber array is a new, promising drug depot
      implantable system that is sensitive to external stimuli.

PMID- 30299077
TI  - Lithium- and Magnesium-Storage Mechanisms of Novel Hexagonal NbSe2.
AB  - As a novel and potential transition metal dichalcogenide (TMDC), NbSe2 has low
      ion diffusion barrier when applied in energy-storage systems, such as traditional
      lithium-ion batteries and novel magnesium-ion batteries (MIBs). In this work, we
      have developed a novel hexagonal NbSe2 material with a nanosized surface via a
      facile microwave-hydrothermal method. The Li+-storage mechanism of NbSe2 with
      surface conversion and internal intercalation is thoroughly revealed by in situ X
      ray diffraction (XRD), ex situ high-resolution transmission electron microscopy,
      and ex situ scanning electron microscopy. Besides, Mg2+ intercalation mechanism
      is confirmed via ex situ XRD and ex situ X-ray photoelectron spectroscopy for the
      first time. In addition, as the cathode for MIBs, NbSe2 with a nanosized surface
      exhibits a high rate capacity of 101 mA h g-1 at 200 mA g-1 with a high discharge
      plateau at 1.30 V. Our work builds a deep understanding of ion-storage mechanisms
      in TMDCs and provides guidance for designing new electrode materials with high
      electrochemical performances.

PMID- 30299078
TI  - Abrupt Thermal Shock of (NH4)2Mo3S13 Leads to Ultrafast Synthesis of Porous
      Ensembles of MoS2 Nanocrystals for High Gain Photodetectors.
AB  - Ultrafast synthesis of high-quality transition-metal dichalcogenide nanocrystals,
      such as molybdenum disulfide (MoS2), is technologically relevant for large-scale
      production of electronic and optoelectronic devices. Here, we report a rapid
      solid-state synthesis route for MoS2 using the chemically homogeneous molecular
      precursor, (NH4)2Mo3S13.H2O, resulting in nanoparticles with estimated size down
      to 25 nm only in 10 s at 1000  degrees C. Despite the extreme nonequilibrium
      conditions, the resulting porous MoS2 nanoparticles remain aggregated to preserve
      the form of the original rod shape bulk morphology of the molecular precursor.
      This ultrafast synthesis proceeds through the rapid decomposition of the
      precursor and rearrangement of Mo and S atoms coupled with simultaneous efficient
      release of massive gaseous species, to create nanoscale porosity in the resulting
      isomorphic pseudocrystals, which are composed of the MoS2 nanoparticles. Despite
      the very rapid escape of massive amounts of NH3, H2O, H2S, and S gases from the
      (NH4)2Mo3S13.H2O mm sized crystals, they retain their original shape as they
      convert to MoS2 rather than undergo explosive destruction from the rapid escape
      process of the gases. The obtained pseudocrystals are made of aggregated MoS2
      nanocrystals exhibit a Brunauer-Emmett-Teller surface area of ~35 m2/g with an
      adsorption average pore width of ~160 A. The nanoporous MoS2 crystals are
      solution processable by dispersing in ethanol and water and can be cast into
      large-area uniform composite films. Photodetectors fabricated from these films
      show more than 2 orders of magnitude higher conductivity (~6.25 * 10-6 S/cm) and
      photoconductive gain (20 mA/W) than previous reports of MoS2 composite films. The
      optoelectronic properties of this nanoporous MoS2 imply that the shallow defects
      that originate from the ultrafast synthesis act as sensitizing centers that
      increase the photocurrent gain via two-level recombination kinetics.

PMID- 30299079
TI  - Distinguishing Core and Antenna Fucosylated Glycopeptides Based on Low-Energy
      Tandem Mass Spectra.
AB  - A straightforward approach has been developed to distinguish core and antenna
      fucosylation in glycopeptides. The method does not require derivatization and can
      be easily adapted into a proteomics workflow. The key aspect is to use low
      collision energy collision-induced dissociation (CID) (on a quadrupole time-of
      flight type instrument) when only single-step fragmentation processes occur. Low
      collision energy should show the precursor ion as the largest peak in the
      spectrum; the survival yield should be ideally over 50%, and this is obtained at
      a collision energy ca. 30% of that typically used for proteomics. In such a case,
      interfering processes like fucose migration or consecutive reactions are
      minimized. Core and antenna fucosylation can be discriminated using various ion
      abundance ratios. Low-energy CID spectra are very "clean" (no chemical noise),
      and the ions used for locating the fucose are among the major peaks, making the
      method well-suited for analytical work. Monitoring the change in the proportion
      of core and antenna fucosylation at the same glycosylation site is also feasible.

PMID- 30299080
TI  - Induced Aggregation and Synergistic Coordination Strategy in Cluster Organic
      Architectures.
AB  - Developments in strategies for the synthesis of oxo-hydroxo lanthanide (Ln)
      clusters during the past few decades have resulted in abundant relevant
      crystalline materials that exhibit attractive structures and interesting
      properties. The combination of these oxo-hydroxo Ln clusters and organic ligands
      has led to the formation of new extended arrays of Ln cluster organic frameworks
      (LnCOFs). In contrast to metal-organic frameworks, the incorporation of
      particular characteristics of clusters provides the opportunity to develop
      performances not available in single-metal compounds. Even with steady advances
      in oxo-hydroxo Ln clusters, progress in LnCOFs is less developed. To obtain
      LnCOFs, one premise is to induce the oxophilic Ln ions undergoing aggregation.
      Meanwhile, the organic ligands should have extra coordination sites for further
      expansion. Multidentate organic ligands like pyrazinecarboxylic acid and
      pyridinecarboxylic acid containing O and N donors will meet these two
      requirements. Their carboxyl groups will induce the aggregation of Ln ions, while
      the N donors can serve as potential extension sites. To make more open frameworks
      or if the oxo-hydroxo Ln clusters fail to be congregated or connected, then a
      second ligand is necessary. The introduction of the suitable second ligand may
      occupy a partial coordination sphere of Ln ions and ultimately benefit the
      connection process. In this Account, we introduce the origin and evolution of the
      induced aggregation and synergistic coordination strategy. According to the
      attributes of the organic ligands in the documented LnCOFs, we classify them into
      linear and nonlinear groups in the second and third parts. From the aspect of
      ligand-induced aggregation, isonicotinic acid (HIN) and lengthened 4-(4
      pyridyl)benzoic acid (HPBA) ligands as well as their nonlinear analogues are
      settled as typical models. From the aspect of synergistic coordination, chelating
      ligands like 1,2-benzenedicarboxylic acid (1,2-H2BDC) and acetic acid (HOAc) play
      significant roles. Moreover, three types of synergistic coordination are
      discussed in detail: synergistic coordination between two types of organic
      ligands, synergistic coordination between organic and inorganic ligands, and
      simultaneous synergistic coordination of aforementioned two types. From the
      aspect of LnCOF products, in addition to traditional pure LnCOFs, new types of
      heterometallic frameworks containing two types of cluster building units have
      been developed. Although this Account focuses on the nuclearity and coordination
      aspects of LnCOFs, we anticipate that it will stimulate more efforts in the
      further study of their properties beyond the exploratory synthesis. More
      importantly, synergistic coordination may be applied to other systems and inspire
      crystal design and targeted assembly of new functional materials.

PMID- 30299081
TI  - "Reverse Kendrick Mass Defect Analysis": Rotating Mass Defect Graphs to Determine
      Oligomer Compositions for Homopolymers.
AB  - A new approach to determining the repeat unit compositions of homopolymers is
      reported in which a mass defect graph is rotated to zero slope to give a graph
      identical to a Kendrick mass defect graph. Because the Kendrick mass defect (KMD)
      is directly related to the elemental composition of the base unit, the process
      can be reversed. A mass defect graph (fractional m/ z plotted against exact m/ z)
      of a homopolymer can be rotated until the slope of the data points is zero. This
      is equivalent to finding a new constant factor by which the measured exact masses
      would have to be multiplied to create a Kendrick mass defect graph with zero
      slope. The elemental composition of the repeat unit can be determined by matching
      the new factor against the calculated factors for candidate compositions. This
      approach provides some benefits over simply looking for pairs of peaks
      corresponding to oligomer units. The primary benefit is to assist in
      visualization of the data. Rotating the data points corresponding to polymer
      masses to zero slope makes it easier to visualize the polymer data, and it
      facilitates the graphical isolation of polymer masses from background
      interferences. The repeat unit composition is determined not from a single pair
      of peaks but from multiple data points, and systematic errors in mass assignment
      can be visualized as deviations from linearity. Resolution-enhanced KMD graphs
      can be constructed for the calculated repeat unit composition by using fractional
      base units.

PMID- 30299082
TI  - Progress toward Solid State Synthesis by Design.
AB  - Ages of history are defined by the underlying materials that promoted human
      development: stone, bronze, and iron ages. Since the middle of the last century,
      humanity has lived in a silicon age, where the development of the transistor
      ushered in new technologies previously thought inconceivable. But as technology
      has advanced, so have the requirements for new materials to sustain increasing
      physical demands. The field of solid state chemistry is dedicated to the
      discovery of new materials and phenomena, and though most materials discoveries
      in history have been through serendipity rather than careful reaction design, the
      last few decades have seen an increase in the number of materials discovered
      through a consideration of chemical reaction kinetics and thermodynamics.
      Materials by design have changed the way solid state chemists approach the
      synthesis of possible materials with interesting and useful properties. Unlike
      other chemistry subfields such as organic chemistry and biochemistry, solid state
      chemistry does not currently benefit from a toolbox of reactions that can allow
      for the synthesis of any arbitrary material. The diversity and complexity of the
      solid state phase space likely inhibits chemists from ever having such a toolbox.
      However, a thorough understanding of the various synthetic techniques involved in
      the synthesis of stable and metastable solids may be realized through an
      understanding of the reaction kinetics and thermodynamics. In the Account, we
      review the common synthesis techniques involved in the formation of metastable
      materials and break down their underlying chemistry to the simplest reaction
      mechanisms involved. The synthesis reactions of most metastable materials can be
      understood through these three reaction driving parameters, which include the
      exploitation of Le Chatelier's principle, thermo-kinetic reaction coupling, and
      lowering the activation energy of formation of the metastable product, and we
      identify several materials whose syntheses are described either by one or a
      combination of these driving parameters. We identify what exists at the frontier
      of materials discovery by design, including novel applications of supercritical
      fluids for tuning between "gas" and "solvent"-like environments. While
      conventional solvation requires changes in either the temperature or composition
      of the system, supercritical fluid solvation requires only changes in the fluid
      density, which opens up the possibilities for the synthesis of new materials.
      Most importantly, however, we look toward the future of materials synthesis by
      design and see that it must be a collaborative one. At present, chemists design
      materials using knowledge about chemical structure and reactivity but often
      target specific materials with very specific properties. In contrast,
      computational chemists perform calculations on millions of different elemental
      combinations and find many candidates of possible materials with interesting
      properties, though most of these are not realizable synthetically due to
      limitations in reactivity, kinetics, or thermodynamics. Synthetic harmony can be
      achieved through active collaboration and communication between these two
      subfields of chemistry, such that new calculations can incorporate complete
      knowledge about reaction kinetics and thermodynamics, and new syntheses target
      computationally predicted materials derived from an understanding of mapped
      reaction landscapes.

PMID- 30299083
TI  - Fabrication of Glass-Insulated Ultramicrometer to Submicrometer Carbon Fiber
      Electrodes to Support a Single Nanoparticle and Nanoparticle Ensembles in
      Electrocatalytic Investigations.
AB  - We report a procedure to fabricate glass-insulated carbon fiber
      ultramicroelectrodes (CF UMEs) with sizes of 10 and 1 MUm in diameter. CF UMEs of
      theses sizes are commonly insulated with polymer or epoxy resins, which typically
      have pinholes and are less stable and difficult to polish. Through judicious
      choice of polishing materials, the fabrication procedure reported here leads to
      CF UMEs with a surface geometry that, within experimental error, is close to that
      of an inlaid disk. We demonstrate how the hardness factor of commonly used
      polishing materials may alter the geometry of CF UMEs, in which carbon has a
      larger hardness factor compared to other metals (i.e., Pt or Au). Atomic force
      microscopy (AFM) and steady-state voltammetry (SSV) were used to characterize the
      CF UME surface and record the electrochemical response, respectively. These
      results were compared to theoretical values for an inlaid disk UME. Pt
      nanoparticle (NP) collision experiments using electrocatalytic amplification were
      used to deposit an exact number of Pt NPs on a CF UME surface. Surface roughness
      was found to significantly decrease the sticking of Pt NPs on the CF surface,
      compared to the theoretical collision frequency. However, decreasing surface
      roughness through judicious polishing led to good agreement between experimental
      and theoretical collision frequencies of NPs on a CF UME surface, leading to the
      fabrication of NP ensembles of UME dimensions (UME-NPE) and a single-nanoparticle
      UME (SNP-UME). These electrodes were used to record and analyze SSVs for the
      hydrogen evolution reaction (HER) in acidic media.

PMID- 30299085
TI  - Stimuli-Responsive Therapeutic Metallodrugs.
AB  - The success of platinum-based anticancer agents has motivated the exploration of
      novel metal-based drugs for several decades, whereas problems such as drug
      resistance and systemic toxicity hampered their clinical applications and
      efficacy. Stimuli-responsiveness of some metal complexes offers a good
      opportunity for designing site-specific prodrugs to maximize the therapeutic
      efficacy and minimize the side effect of metallodrugs. This review presents a
      comprehensive and up-to-date overview on the therapeutic stimuli-responsive
      metallodrugs that have appeared in the past two decades, where stimuli such as
      redox, pH, enzyme, light, temperature, and so forth were involved. The compounds
      are classified into three major categories based on the nature of stimuli, that
      is, endo-stimuli-responsive metallodrugs, exo-stimuli-responsive metallodrugs,
      and dual-stimuli-responsive metallodrugs. Representative examples of each type
      are discussed in terms of structure, response mechanism, and potential medical
      applications. In the end, future opportunities and challenges in this field are
      tentatively proposed. With diverse metal complexes being introduced, the foci of
      this review are pointed to platinum and ruthenium complexes.

PMID- 30299084
TI  - Expanded Substrate Scope of DNA Polymerase theta and DNA Polymerase beta: Lyase
      Activity on 5'-Overhangs and Clustered Lesions.
AB  - DNA polymerase theta (Pol theta) is a multifunctional enzyme with double-strand
      break (DSB) repair, translesion synthesis, and lyase activities. Pol theta lyase
      activity on ternary substrates containing a 5'-dRP that are produced during base
      excision repair of abasic sites (AP) is weak compared to that of DNA polymerase
      beta (Pol beta), a polymerase integrally involved in base excision repair. This
      led us to explore whether Pol theta utilizes its lyase activity to remove 5'-dRP
      and incise abasic sites from alternative substrates that might be produced during
      DNA damage and repair. We found that Pol theta exhibited lyase activity on abasic
      lesions near DSB termini and on clustered lesions. To calibrate the Pol theta
      activity, Pol beta reactivity was examined with the same substrates. Pol beta
      excised 5'-dRP from within a 5'-overhang 80 times faster than did Pol theta. Pol
      theta and Pol beta also incised AP within clustered lesions but showed opposite
      preferences with respect to the polarity of the lesions. AP lesions in 5'
      overhangs were typically excised by Pol beta 35-50 times faster than those in a
      duplex substrate but 15-20-fold more slowly than 5'-dRP in a ternary complex.
      This is the first report of Pol theta exhibiting lyase activity within an
      unincised strand. These results suggest that bifunctional polymerases may exhibit
      lyase activity on a greater variety of substrates than previously recognized. A
      role in DSB repair could potentially be beneficial, while the aberrant activity
      exhibited on clustered lesions may be deleterious because of their conversion to
      DSBs.

PMID- 30299086
TI  - Nanocellulose toward Advanced Energy Storage Devices: Structure and
      Electrochemistry.
AB  - Cellulose is the most abundant biopolymer on Earth and has long been used as a
      sustainable building block of conventional paper. Note that nanocellulose
      accounts for nearly 40% of wood's weight and can be extracted using well
      developed methods. Due to its appealing mechanical and electrochemical
      properties, including high specific modulus (~100 GPa/(g/cm3)), excellent
      stability in most solvents, and stability over a wide electrochemical window,
      nanocellulose has been widely used as a separator, electrolyte, binder, and
      substrate material for energy storage. Additionally, nanocellulose-derived carbon
      materials have also drawn increasing scientific interest in sustainable energy
      storage due to their low-cost and raw-material abundance, high conductivity, and
      rational electrochemical performance. The inexpensive and environmentally
      friendly nature of nanocellulose and its derivatives as well as simple
      fabrication techniques make nanocellulose-based energy storage devices promising
      candidates for the future of "green" and renewable electronics. For nanocellulose
      based energy storage, structure engineering and design play a vital role in
      achieving desired electrochemical properties and performances. Thus, it is
      important to identify suitable structure and design engineering strategies and to
      better understand their relationship. In this Account, we review recent
      developments in nanocellulose-based energy storage. Due to the limited space, we
      will mainly focus on structure design and engineering strategies in macrofiber,
      paper, and three-dimensional (3D) structured electrochemical energy storage (EES)
      devices and highlight progress made in our group. We first present the structure
      and properties of nanocellulose, with a particular discussion of nanocellulose
      from wood materials. We then go on to discuss studies on nanocellulose-based
      macrofiber, paper, and 3D wood- and other aerogel-based EES devices. Within this
      discussion, we highlight the use of natural nanocellulose as a flexible substrate
      for a macrofiber supercapacitor and an excellent electrolyte reservoir for a
      breathable textile lithium-oxygen battery. Paper batteries and supercapacitors
      using nanocellulose as a green dispersant, nanocellulose-based paper as a
      flexible substrate, and nanocellulose as separator and electrolyte are also
      examined. We highlight recent progress on wood-based batteries and
      supercapacitors, focusing on the advantages of wood materials for energy storage,
      the structure design and engineering strategies, and their microstructure and
      electrochemical properties. We discuss the influence of structure (particularly
      pores) on the electrochemical performance of the energy storage devices. By
      taking advantage of the straight, nature-made channels in wood materials,
      ultrathick, highly loaded, and low-tortuosity energy storage devices are
      demonstrated. Finally, we offer concluding remarks on the challenges and
      directions of future research in the field of nanocellulose-based energy storage
      devices.

PMID- 30299087
TI  - Rationally Optimized Fluorescent Probe for Imaging Mitochondrial SO2 in HeLa
      Cells and Zebrafish.
AB  - Organisms have built up immunological systems, where mitochondrial SO2 plays
      conflicting roles in regulating cell apoptosis. However, no exploration on the
      influence and regulating principle of mitochondrial SO2 to the specific apoptosis
      type can be found, which brings about a challenge to fluorescent probes. Herein,
      we optimize the fluorophore and develop a new fluorescent probe FHMI (( E)-4-(3
      formyl-4-hydroxystyryl)-1-methylpyridin-1-iumiodide) by equipping an ICT
      (intramolecular charge transfer) fluorophore HMII (( E)-4-(4-hydroxystyryl)-1
      methylpyridin-1-ium iodide) with an aldehyde group that serves as both
      fluorescence quencher and reporting group. After the optimization, although the
      nonconjugated electron donor is formed when sensing SO2, the preset ICT
      fluorophore HMII is permitted to release the fluorescence at the enlarged
      wavelength. Compared with the traditional design, the probe FHMI exhibits obvious
      enhanced fluorescence with large red shift. FHMI is successfully applied to the
      mechanistic exploration of the dichotomous effects of mitochondrial SO2 to cells
      apoptosis, showing that mitochondrial SO2 regulates the early apoptosis of HeLa
      cells via the reduction of mitochondrial membrane potential. FHMI is applied to
      explore the dichotomous bioinfluence of mitochondrial SO2 to HeLa cells under
      oxidative stress, visualizing the regulative role of mitochondrial SO2 in the
      apoptotic process. For the first time, the mitochondrial SO2 is visually found to
      be closely associated with the early apoptosis of HeLa cells. Moreover, FHMI
      proves to be readily applicable to monitoring endogenous SO2 in zebrafish. This
      probe can act as an effective optical tool for exploring SO2 in biospecimen.

PMID- 30299088
TI  - Radioactive Transition Metals for Imaging and Therapy.
AB  - Nuclear medicine is composed of two complementary areas, imaging and therapy.
      Positron emission tomography (PET) and single-photon imaging, including single
      photon emission computed tomography (SPECT), comprise the imaging component of
      nuclear medicine. These areas are distinct in that they exploit different nuclear
      decay processes and also different imaging technologies. In PET, images are
      created from the 511 keV photons produced when the positron emitted by a
      radionuclide encounters an electron and is annihilated. In contrast, in single
      photon imaging, images are created from the gamma rays (and occasionally X-rays)
      directly emitted by the nucleus. Therapeutic nuclear medicine uses particulate
      radiation such as Auger or conversion electrons or beta- or alpha particles. All
      three of these technologies are linked by the requirement that the radionuclide
      must be attached to a suitable vector that can deliver it to its target. It is
      imperative that the radionuclide remain attached to the vector before it is
      delivered to its target as well as after it reaches its target or else the
      resulting image (or therapeutic outcome) will not reflect the biological process
      of interest. Radiochemistry is at the core of this process, and radiometals offer
      radiopharmaceutical chemists a tremendous range of options with which to
      accomplish these goals. They also offer a wide range of options in terms of
      radionuclide half-lives and emission properties, providing the ability to
      carefully match the decay properties with the desired outcome. This Review
      provides an overview of some of the ways this can be accomplished as well as
      several historical examples of some of the limitations of earlier
      metalloradiopharmaceuticals and the ways that new technologies, primarily related
      to radionuclide production, have provided solutions to these problems.

PMID- 30299089
TI  - Highly Active Protein Surfaces Enabled by Plant-Based Polyphenol Coatings.
AB  - Proteins represent complex biomolecules capable of wide-ranging but also highly
      specific functionalities. Their immobilization on material supports can enable
      broad applications from sensing and industrial biocatalysis to biomedical
      interfaces and materials. We demonstrate the advantages of using aqueous
      processed cross-linked polyphenol coatings for immobilizing proteins, including
      IgG, avidin, and various single and multidomain enzymes on diverse materials, to
      enable active biofunctional structures (e.g., ca. 2.2, 1.7, 1.1, and 4.8 mg.m-2
      active phosphatase on nanoporous cellulose and alumina, steel mesh, and polyester
      fabric, respectively). Enzyme assays, X-ray photoelectron spectroscopy, silver
      staining, supplemented with contact angle, solid-state 13C NMR, HPLC, and ESI-MS
      measurements were used to characterize the polyphenols, coatings, and protein
      layers. We show that the functionalization process may be advantageously
      optimized directly for protein activity rather than the traditional focus on the
      thickness of the coating layer. Higher activities (by more than an order of
      magnitude in some cases) and wider process pH and material compatibility are
      demonstrated with polyphenol coatings than other approaches such as polydopamine.
      Coatings formed from different plant polyphenol extracts, even at lowered purity
      (and cost), were also found to be highly functional. Chemically, our results
      indicate that polyphenol coatings differ from polydopamine mainly because of the
      elimination of amine groups, and that polyphenol layers with intermediate levels
      of reactivity may better lead to high immobilized protein activity. Overall, an
      improved understanding of simple-to-use polyphenol coatings has been obtained,
      which enabled a significant development in active protein surfaces that may be
      applied across diverse materials and nanostructured supports.

PMID- 30299090
TI  - Nanotubes, Plates, and Needles: Pathway-Dependent Self-Assembly of
      Computationally Designed Peptides.
AB  - Computationally designed peptides form desired antiparallel, tetrameric coiled
      coil bundles that hierarchically assemble into a variety of well-controlled
      nanostructures depending on aqueous solution conditions. The bundles selectively
      self-assemble into different structures: nanotubes, platelets, or needle-like
      structures at solution pH values of 4.5, 7, and 10, respectively. The self
      assembly produces hollow tubes or elongated needle-like structures at pH
      conditions associated with charged bundles (pH 4.5 or 10); at neutral pH, near
      the pI of the bundle, a plate-like self-assembled structure forms. Transmission
      electron microscopy and small-angle X-ray scattering show the nanotubes to be
      uniform with a tube diameter of ~13 nm and lengths of up to several MUm, yielding
      aspect ratios >1000. Combining the measured nanostructure geometry with the
      apparent charged states of the constituent amino acids, a tilted-bundle packing
      model is proposed for the formation of the homogeneous nanotubes. This work
      demonstrates the successful use of assembly pathway control for the construction
      of nanostructures with diverse, well-structured morphologies associated with the
      folding and self-association of a single type of molecule.

PMID- 30299091
TI  - A Langbeinite-Type Yttrium Phosphate LiCs2Y2(PO4)3.
AB  - Langbeinite-type inorganic compounds have a wide range of applications, but
      nonlinear-optical properties are rarely mentioned in this series. Here, we report
      a new orthophosphate, LiCs2Y2(PO4)3, with a langbeinite-type structure, which is
      the first example in the system of mixed alkali-metal yttrium phosphates.
      Notably, LiCs2Y2(PO4)3 exhibits a moderate second-harmonic-generation efficiency
      of 0.9KH2PO4 and is transparent down to 200 nm. In addition, the thermal
      stability and theory calculations, including the electronic band structure,
      second-order nonlinear-optical coefficients, and dipole moment analysis, are also
      reported. This work not only expands the langbeinite-type system but also
      inspires a study on their nonlinear-optical properties.

PMID- 30299092
TI  - Laboratory Studies of Vibrational Excitation in O2( a1Deltag, v) Involving O2,
      N2, and CO2.
AB  - Collisional removal of electronic energy from O2 in the low-lying a1Deltag state
      is typically an extremely slow process for the v = 0 level. In this study, we
      report results on the deactivation of O2( a1Deltag, v = 1-3) in collisions with
      O2 and CO2. Ozone photodissociation in the 200-310 nm Hartley band is the source
      of O2( a, v), and resonance-enhanced multiphoton ionization is used to probe the
      vibrational-level populations. Deactivation of the a( v = 1-3) levels in
      collisions with O2 at 300 K is fast, with rate coefficients of (5.6 +/- 1.1) * 10
      11, (3.6 +/- 0.4) * 10-11, and (1.9 +/- 0.4) * 10-11 cm3 s-1 (2sigma) for v = 1,
      2, and 3, respectively. The relaxation process appears to involve a near-resonant
      electronic energy transfer pathway analogous to that observed in vibrationally
      excited O2( b1Sigmag+). With CO2 collider gas, the removal rate coefficient at
      300 K is (1.8 +/- 0.4) * 10-14 and (4.4 +/- 0.6) * 10-14 cm3 s-1 (2sigma) for v =
      1 and 2, respectively. Despite the small mole fraction of O2 in the atmospheres
      of Mars and Venus, O2 is at least as important as CO2 in the final stages of
      collisional relaxation within the O2 vibrational-level manifold.

PMID- 30299093
TI  - Exhaustive Exploration of the Conformational Landscape of Small Cyclic Peptides
      Using a Robotics Approach.
AB  - Small cyclic peptides represent a promising class of therapeutic molecules with
      unique chemical properties. However, the poor knowledge of their structural
      characteristics makes their computational design and structure prediction a real
      challenge. In order to better describe their conformational space, we developed a
      method, named EGSCyP, for the exhaustive exploration of the energy landscape of
      small head-to-tail cyclic peptides. The method can be summarized by (i) a global
      exploration of the conformational space based on a mechanistic representation of
      the peptide and the use of robotics-based algorithms to deal with the closure
      constraint and (ii) an all-atom refinement of the obtained conformations. EGSCyP
      can handle D-form residues and N-methylations. Two strategies for the side-chains
      placement were implemented and compared. To validate our approach, we applied it
      to a set of three variants of cyclic RGDFV pentapeptides, including the drug
      candidate Cilengitide. A comparative analysis was made with respect to replica
      exchange molecular dynamics simulations in implicit solvent. Its results show
      that the EGSCyP method provides a very complete characterization of the
      conformational space of small cyclic pentapeptides.

PMID- 30299094
TI  - Computational Strategy for Bound State Structure Prediction in Structure-Based
      Virtual Screening: A Case Study of Protein Tyrosine Phosphatase Receptor Type O
      Inhibitors.
AB  - Accurate protein structure in the ligand-bound state is a prerequisite for
      successful structure-based virtual screening (SBVS). Therefore, applications of
      SBVS against targets for which only an apo structure is available may be severely
      limited. To address this constraint, we developed a computational strategy to
      explore the ligand-bound state of a target protein, by combined use of molecular
      dynamics simulation, MM/GBSA binding energy calculation, and fragment-centric
      topographical mapping. Our computational strategy is validated against low
      molecular weight protein tyrosine phosphatase (LMW-PTP) and then successfully
      employed in the SBVS against protein tyrosine phosphatase receptor type O
      (PTPRO), a potential therapeutic target for various diseases. The most potent hit
      compound GP03 showed an IC50 value of 2.89 MUM for PTPRO and possessed a certain
      degree of selectivity toward other protein phosphatases. Importantly, we also
      found that neglecting the ligand energy penalty upon binding partially accounts
      for the false positive SBVS hits. The preliminary structure-activity
      relationships of GP03 analogs are also reported.

PMID- 30299095
TI  - Bottom-Up Assembly of a Highly Efficient Metal-Organic Framework for Cooperative
      Catalysis.
AB  - In this study, we demonstrate a bottom-up assembly of a monomeric copper complex
      and a two-dimensional (2-D) heterometallic metal-organic framework (MOF) from a
      carboxylate-functionalized tridentate Schiff base ligand and metal ions. The
      obtained 2-D MOF features a unique bimetallic copper center which is different
      from its monometallic precursor and acts as an efficient heterogeneous catalyst
      for the Friedel-Crafts reaction and Henry reaction. The MOF catalyst shows a
      remarkably superior activity compared to its homogeneous counterparts in a wide
      range of substrates. It is presumably ascribed to the dual activation of the
      substrates by the active bimetallic copper center confined in the MOF network,
      which is supported by the significant changes in catalytic activity at low
      catalyst/substrates ratios when using the 2-D MOF and its precursor as catalysts,
      respectively. Moreover, the MOF catalyst also shows an excellent stability and
      recyclability. Our work, therefore, provides a stepwise strategy to design a
      heterogeneous cooperative catalyst, by taking advantage of the modulated
      structure of MOF and tunable functionality of the tridentate Schiff base, with
      high performance in a variety of organic synthesis.

PMID- 30299096
TI  - Spatial Distribution of Collections Yielding Marine Natural Products.
AB  - The societal benefits of coral reef ecosystems include shoreline protection,
      habitat provision for reef fish, tourism, and recreation. Rarely considered in
      valuation of reefs is the considerable contribution of marine natural products
      (MNPs) to both human health and the economy. To better understand the relation of
      MNP discovery with the characteristics and condition of coral reef ecosystems, we
      initiated a study to track the collection location and taxonomic identity of
      organisms that have provided pharmacological products. We reviewed collection
      information and associated data from 298 pharmacological products originating
      from marine biota during the past 47 years. The products were developed from 232
      different marine species representing 15 phyla, and the 1296 collections of these
      specimens occurred across 69 countries and seven continents. Our evaluation of
      the collection data was hampered by sundry observational and reporting issues,
      including imprecise location descriptions and omission of collection dates.
      Nonetheless, the study provides an important synopsis and appraisal of years of
      study and exploration by the marine natural product community. Understanding and
      quantifying the benefits of MNP discovery will depend upon improved reporting of
      collections, including accurate taxonomic identification, collection dates, and
      locations.

PMID- 30299097
TI  - Charge Transport in [Li(tetraglyme)][bis(trifluoromethane) sulfonimide] Solvate
      Ionic Liquids: Insight from Molecular Dynamics Simulations.
AB  - Molecular dynamics simulations using fully atomistic polarizable force field have
      been performed on solvate ionic liquids (SILs), comprised of tetraglyme (G4)
      solvent molecules, Li+ cations, and bis(trifluoromethane) sulfonimide (TFSI)
      anions, [Li(G4)][TFSI]. The SILs with equimolar salt:G4 composition were
      investigated in the 303-373 K temperature range, whereas several systems with
      lower salt concentrations were investigated at 373 K. The simulations using
      polarizable force field demonstrate very good consistency of structural and
      dynamic properties with experimental data. The ability to accurately sample the
      ion transport mechanisms is particularly encouraging, taking into account that
      previous simulations employing nonpolarizable models had challenges in sampling
      dynamics in these systems. Here, we correlate Li+ ion local environment and glyme
      conformations with dynamic characteristics, such as residence time of species
      around Li+, self-diffusion coefficients, transference number, and conductivity.
      The analysis of contributions to Li+ mobility due to changing its local
      environment (i.e., moving from one glyme/anion to another) and from translational
      motion of Li+ with its' coordination environment showed significant dominance of
      the latter. The contributions of cross-ion dynamic correlations to the total
      conductivity have been quantified, showing strongly positive contribution from
      the cation-anion anticorrelation. Despite the high degree of Li-TFSI dissociation
      and positive contribution of the cation-anion anticorrelated motion to
      conductivity, the Li+ transference numbers for equimolar SILs are very low under
      the anion blocking conditions.

PMID- 30299098
TI  - Ground State Nuclear Magnetic Resonance Chemical Shifts Predict Charge-Separated
      Excited State Lifetimes.
AB  - Dichalcogenolene platinum(II) diimine complexes, (LE,E')Pt(bpy), are
      characterized by charge-separated dichalcogenolene donor (LE,E') -> diimine
      acceptor (bpy) ligand-to-ligand charge transfer (LL'CT) excited states that lead
      to their interesting photophysics and potential use in solar energy conversion
      applications. Despite the intense interest in these complexes, the chalcogen
      dependence on the lifetime of the triplet LL'CT excited state remains
      unexplained. Three new (LE,E')Pt(bpy) complexes with mixed chalcogen donors
      exhibit decay rates that are dominated by a spin-orbit mediated nonradiative
      pathway, the magnitude of which is proportional to the anisotropic covalency
      provided by the mixed-chalcogen donor ligand environment. This anisotropic
      covalency is dramatically revealed in the 13C NMR chemical shifts of the donor
      carbons that bear the chalcogens and is further probed by S K-edge XAS.
      Remarkably, the NMR chemical shift differences also correlate with the spin-orbit
      matrix element that connects the triplet excited state with the ground state.
      Consequently, triplet LL'CT excited state lifetimes are proportional to both
      functions, demonstrating that specific ground state NMR chemical shifts can be
      used to evaluate spin-orbit coupling contributions to excited state lifetimes.

PMID- 30299099
TI  - N-Arylation of Carbamates through Photosensitized Nickel Catalysis.
AB  - A highly efficient method of visible light mediated Ni(II)-catalyzed photoredox N
      arylation of Cbz-amines/Boc-amines with aryl electrophiles at room temperature is
      reported. The methodology provides a common access to a wide variety of N
      aromatic and N-heteroaromatic carbamate products that find use in the synthesis
      of several biologically active molecules and provides a distinct advantage over
      traditional palladium-catalyzed Buchwald reaction.

PMID- 30299100
TI  - Volatility of Amorphous Solid Water.
AB  - Amorphous solid water is probably the most abundant form of solid water in the
      universe. Its saturation vapor pressure and thermodynamic properties, however,
      are not well known. We have investigated the saturation vapor pressure over vapor
      deposited amorphous ice at temperatures between 133 and 147 K using a novel
      experimental method. The new method determines the absolute vapor pressures and
      the sublimation rates by measuring the mass growth rates of ice-covered
      nanoparticles under supersaturated water vapor conditions. We find that the vapor
      pressure of amorphous solid water is up to a factor of 3 higher than that
      predicted by current parameterizations, which are based in part on calorimetric
      measurements. We demonstrate that the calorimetric measurements can be reconciled
      with our data by acknowledging the formation of nanocrystalline ice as an
      intermediate ice phase during the crystallization of amorphous ice. As a result,
      we propose a new value for the enthalpy of crystallization of amorphous solid
      water of Delta H = 2312 +/- 227 J/mol, which is about 1000 J/mol higher than the
      current consensus. Our results shine a new light on the abundance of water ice
      clouds on Mars and mesospheric clouds on Earth and may alter our understanding of
      ice formation in the stratosphere.

PMID- 30299101
TI  - Accurate Predictions of Electron Binding Energies of Dipole-Bound Anions via
      Quantum Monte Carlo Methods.
AB  - Neutral molecules with sufficiently large dipole moments can bind electrons in
      diffuse nonvalence orbitals with most of their charge density far from the
      nuclei, forming so-called dipole-bound anions. Because long-range correlation
      effects play an important role in the binding of an excess electron and overall
      binding energies are often only on the order of 10s-100s of wave numbers,
      predictively modeling dipole-bound anions remains a challenge. Here, we
      demonstrate that quantum Monte Carlo methods can accurately characterize
      molecular dipole-bound anions with near-threshold dipole moments. We also show
      that correlated sampling Auxiliary Field Quantum Monte Carlo is particularly well
      suited for resolving the fine energy differences between the neutral and anionic
      species. These results shed light on the fundamental limitations of quantum Monte
      Carlo methods and pave the way toward using them for the study of weakly bound
      species that are too large to model using traditional electron structure methods.

PMID- 30299102
TI  - Electron Paramagnetic Resonance and Small-Angle X-ray Scattering Characterization
      of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Dibucaine
      Encapsulation.
AB  - Dibucaine (DBC) is one of the most potent long-acting local anesthetics, but it
      also has significant toxic side effects and low water solubility. Solid lipid
      nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been proposed
      as drug-delivery systems to increase the bioavailability of local anesthetics.
      The purpose of the present study was to characterize SLNs and NLCs composed of
      cetyl palmitate or myristyl myristate, a mixture of capric and caprylic acids
      (for NLCs only) plus Pluronic F68 prepared for the encapsulation of DBC. We
      intended to provide a careful structural characterization of the nanoparticles to
      identify the relevant architectural parameters that lead to the desirable
      biological response. Initially, SLNs and NLCs were assessed in terms of their
      size distribution, morphology, surface charge, and drug loading. Spectroscopic
      techniques (infrared spectroscopy and electron paramagnetic resonance, EPR) plus
      small-angle X-ray scattering (SAXS) provided information on the interactions
      between nanoparticle components and their structural organization. The sizes of
      nanoparticles were in the 180 nm range with low polydispersity and negative zeta
      values (-25 to -46 mV). The partition coefficient of DBC between nanoparticles
      and water at pH 8.2 was very high (>104). EPR (with doxyl-stearate spin labels)
      data revealed the existence of lamellar arrangements inside the lipid
      nanoparticles, which was also confirmed by SAXS experiments. Moreover, the
      addition of DBC increased the molecular packing of both SLN and NLC lipids,
      indicative of DBC insertion between the lipids, in the milieu assessed by spin
      labels. Such structural information brings insights into understanding the
      molecular organization of these versatile drug-delivery systems which have
      already demonstrated their potential for therapeutic applications in pain
      control.

PMID- 30299103
TI  - Mutational Basin-Hopping: Combined Structure and Sequence Optimization for
      Biomolecules.
AB  - The study of energy landscapes has led to a good understanding of how and why
      proteins and nucleic acids adopt their native structure. Through evolution,
      sequences have adapted until they exhibit a strongly funneled energy landscape,
      stabilizing the native fold. Design of artificial biomolecules faces the
      challenge of creating similar stable, minimally frustrated, and functional
      sequences. Here we present a biminimization approach, mutational basin-hopping,
      in which we simultaneously use global optimization to optimize the energy and a
      target function describing a desired property of the system. This optimization of
      structure and sequence is a generalized basin-hopping method and produces an
      efficient design process, which can target properties such as binding affinity or
      solubility.

PMID- 30299104
TI  - 1,2-Epoxyalkane: Another Precursor for Fabricating Alkoxy Self-Assembled
      Monolayers on Hydrogen-Terminated Si(111).
AB  - This work describes the UV alkoxylation of a series of 1,2-epoxyalkanes on the
      hydrogen-terminated silicon (H-Si) substrate. The formation of alkoxy self
      assembled monolayers (SAMs) and the nature of bonding at the surface of H-Si were
      examined using water contact angle goniometer, spectroscopic ellipsometer,
      Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy
      (XPS), and atomic force microscopy. UV exposure to 1,2-epoxyalkane mesitylene
      solution for 60 min formed alkoxy-SAMs onto H-Si with hydrophobic properties. The
      local molecular environment of the alkyl chains transitioned from a disordered,
      liquid-like state to an ordered, crystalline-like structure with increasing the
      chain length. XPS and FTIR indicated that the reaction of H-Si with 1,2
      epoxyalkane produced Si-O-C linkages. The Si-H bond homolysis and electron/hole
      were the plausible mechanistic routes for the grafting of 1,2-epoxyalkanes.

PMID- 30299105
TI  - Assessment of Th1/Th2 Bias of STING Agonists Coated on Microneedles for Possible
      Use in Skin Allergen Immunotherapy.
AB  - Microneedle-based skin allergen-specific immunotherapy (AIT) can benefit from
      adjuvants that can stimulate a stronger Th1 response against the allergen. We
      evaluated two stimulator of interferon genes (STING) agonists, namely, cyclic
      diguanylate monophosphate (c-di-GMP) and cyclic diadenylate monophosphate (c-di
      AMP), as skin adjuvants using coated microneedles (MNs). For comparison, the
      approved subcutaneous (SC) hypodermic injection containing alum was used.
      Ovalbumin (Ova) was used as a model allergen. Ova-specific IgG2a antibody in
      serum, which is a surrogate marker for Th1 type immune response was significantly
      higher when STING agonists were used with coated MNs as compared to SC injection
      of Ova+alum in mice. In contrast, IgG1 antibody, a surrogate marker for Th2 type
      immune response, was at comparable levels in the MN and SC groups. Restimulation
      of splenocytes with Ova produced higher levels of Th1 cytokines (IFN-gamma and IL
      2) in the STING agonists MN groups as compared to the SC group. In conclusion,
      delivery of STING agonists into the skin using coated MNs activated the Th1
      pathway better than SC- and MN-based delivery of alum. Thus, STING agonists could
      fulfill the role of adjuvants for skin AIT and even for infectious disease
      vaccines, where stimulation of the Th1 pathway is of interest.

PMID- 30299107
TI  - Cementation and Bonding of Zirconia Restorations.

PMID- 30299106
TI  - Mechanism of Goethite Precipitation on Magnetite and Maghemite Nanoparticles
      Studied by Surface Complexation/Precipitation Modeling.
AB  - Precipitation of goethite on magnetic nanoparticles (MNPs) has been proposed as
      an effective means to separate goethite from calcium sulfate in the iron removal
      process of zinc hydrometallurgy, which allows reuse of the hazardous residues.
      This study focuses on investigating the underlying mechanisms of goethite
      precipitation on magnetite and maghemite MNPs, providing insights on Fe(III)aq
      adsorption and nucleation of goethite on MNPs. A predictive surface
      complexation/precipitation model of the system was developed based on the results
      from two different types of experiments: the potentiometric titration of MNPs to
      calculate proton binding constants ( Ka) of discrete MNP surface functional
      groups and the corresponding site concentrations; and adsorption of Fe(III)aq
      onto MNP surfaces to determine metal binding constants ( Kf). The composition of
      the surface complexes on MNPs was determined by time-of-flight secondary ion mass
      spectrometry. The results indicated the formation of polynuclear surface
      complexes. The content of polynuclear surface complexes was found to be
      significantly higher on maghemite MNPs than on magnetite MNPs. This trend is
      consistent with our experimental results of a greater goethite precipitation on
      maghemite than on magnetite. Overall, the formation of Fe(III) polynuclear
      surface complexes correlates directly to the nucleation and precipitation of
      goethite on the surfaces of both types of MNPs.

PMID- 30299108
TI  - Zirconia: The Material, Its Evolution, and Composition.

PMID- 30299109
TI  - A New Perspective: From Ordinary to Extraordinary.

PMID- 30299110
TI  - Effects of Occlusion on Periodontal Wound Healing.
AB  - Trauma from occlusion remains an important concept in dentistry. Traumatic
      occlusion affects the biological system through a series of events that induces
      an aseptic inflammatory response and bone resorption. Clinical evidence of these
      biological events is present in the form of active traumatic lesions or adaptive
      mechanisms. If these clinical signs are not identified prior to periodontal
      surgery, failure of the procedure could result due to an exacerbated leukocyte
      presence and unresolving wound. However, if traumatic occlusion is adjusted,
      evidence demonstrates that even large inflammatory events such as replantation of
      an avulsed tooth can be successful. Thus, harmony of occlusal contacts without
      interference is essential in achieving predictable periodontal/implant bone
      regeneration.

PMID- 30299111
TI  - Dynamic Navigation for Surgical Implant Placement: Overview of Technology, Key
      Concepts, and a Case ReportDynamic Navigation for Surgical Implant Placement:
      Overview of Technology, Key Concepts, and a Case Report.
AB  - Over the course of several decades implant dentistry has evolved to include 3
      dimensionally (3D) planned and guided surgery. One of the latest innovations is
      dynamic navigation, which may allow surgeons to place implants with accuracy
      similar to stereolithographic guides based on 3D, prosthetically directed plans.
      Benefits of dynamically guided surgery include real-time feedback, a streamlined
      digital workflow, improved surgical visualization, and adaptability to
      intraoperative findings. This article discusses the technology and workflow of
      dynamic navigation and its application for guided implant placement.
      Additionally, a case completed using this technology is presented.

PMID- 30299112
TI  - Circumferential Occlusal Access Procedure (COAP): Novel Minimally Invasive
      Surgical Approach for Treatment of Peri-Implantitis- A Case Series.
AB  - Treatment of peri-implantitis is typically most successful when a full-thickness
      surgical flap is elevated to access the contaminated implant surface and the bone
      loss that has occurred. This approach, however, can be problematic. Primary flap
      approximation can be challenging after a regenerative procedure, especially with
      a shallow vestibule, thin mucosa, or minimal zone of keratinized tissue.
      Incomplete wound closure and soft-tissue dehiscence can lead to membrane and
      graft exposure. In medicine, minimally invasive techniques have been developed
      and are being used in an increasing variety of procedures. This article will
      present the circumferential occlusal access procedure (COAP), a minimally
      invasive, flapless surgical technique designed to access and detoxify a
      contaminated implant surface and facilitate bone repair or regeneration while
      reducing the potential for membrane exposure and recession.

PMID- 30299114
TI  - Dentin Adhesives: Essential Components to Successful Conservative Dentistry.

PMID- 30299113
TI  - Zygomatic Implants for the Management of Severe Alveolar Atrophy in the Partial
      or Completely Edentulous Maxilla.
AB  - Treatment of severely resorbed partially or completely edentulous maxillae can
      include the utilization of the zygomatic process for immediate implant fixation
      and stabilization with immediate function. This approach may alleviate the need
      for significant grafting to enable implant placement in the posterior maxilla and
      allow implants to be placed into denser, more stable bone. Zygomatic implants,
      which have been used clinically for the past 20 years in the treatment of the
      severely resorbed maxilla, allow implant placement to support fixed prosthetics.
      Their usage can potentially shorten treatment time and reduce costs, as the need
      to wait for osseous graft maturation is eliminated. Guided surgical approaches
      are being utilized to maximize placement of the prosthetic platform of these
      implants.

PMID- 30299115
TI  - The impact of leader moral humility on follower moral self-efficacy and behavior.
AB  - This study utilizes social-cognitive theory, humble leadership theory, and the
      behavioral ethics literature to theoretically develop the concept of leader moral
      humility and its effects on followers. Specifically, we propose a theoretical
      model wherein leader moral humility and follower implicit theories about morality
      interact to predict follower moral efficacy, which in turn increases follower
      prosocial behavior and decreases follower unethical behavior. We furthermore
      suggest that these effects are strongest when followers hold an incremental
      implicit theory of morality (i.e., believing that one's morality is malleable).
      We test and find support for our theoretical model using two multiwave studies
      with Eastern (Study 1) and Western (Study 2) samples. Furthermore, we demonstrate
      that leader moral humility predicts follower moral efficacy and moral behaviors
      above and beyond the effects of ethical leadership and leader general humility.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299116
TI  - Assessing suicidality in real time: A psychometric evaluation of self-report
      items for the assessment of suicidal ideation and its proximal risk factors using
      ecological momentary assessments.
AB  - Suicidal ideation is a major risk factor for suicidal behavior and has recently
      been shown to be fluctuating in studies applying ecological momentary assessments
      (EMAs). The aims of this study are to introduce a reliable and valid item set for
      assessing suicidal ideation and relevant proximal risk factors that can be used
      in future EMA studies within suicidology. Additionally, we provide data on the
      ability of the items to capture moment-to-moment variability and discuss
      feasibility aspects of EMA studies on suicidal ideation in a clinical sample.
      Psychiatric inpatients diagnosed with a depressive disorder (N = 74) rated a set
      of 28 items measuring suicidal ideation, thwarted belongingness, perceived
      burdensomeness, depression, anxiety, hopelessness, and positive affect 10 times
      per day on 6 consecutive days. In addition, these constructs were assessed by
      self-report questionnaires before and after the EMA period. Intraclass
      correlations and mean squared successive differences were calculated as
      indicators of item variability. Reliability was calculated at the prompt (within
      person) and the person (between-person) level, applying an approach based on
      multilevel factor analysis. Convergent validity was assessed by correlating the
      EMA scores with a self-report questionnaire measuring the same constructs. All
      items demonstrated moment-to-moment-variability and substantial within-person
      variance. Moreover, all items and scales, except those assessing anxiety, showed
      satisfying reliability at the prompt and the person level, and correlations
      indicated convergent validity of the EMA item set. Compliance with the EMAs was
      excellent (89.7%). Researchers are encouraged to apply this useful tool in future
      EMA studies in the field of suicidology. (PsycINFO Database Record (c) 2018 APA,
      all rights reserved).

PMID- 30299117
TI  - Target rotation with both factor loadings and factor correlations.
AB  - Factor rotation is conducted to aid interpretation in exploratory factor analysis
      (EFA). Target rotation allows researchers to directly examine the match between
      the rotated factor loading matrix and their expected factor loading pattern. In
      some EFA applications, however, researchers have expectations on both the factor
      loading pattern and the factor correlation pattern. We propose to extend target
      rotation such that target values can be specified for both factor loadings and
      factor correlations. We illustrate extended target rotation with a memory study
      and a personality study with the multitrait-multimethod design. We also explore
      the statistical properties of extended target rotation using simulated data.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299118
TI  - True virtue, self-presentation, or both?: A behavioral test of impression
      management and overclaiming.
AB  - Measures of self-favoring response biases such as impression management (IM)
      scales or the overclaiming technique (OCT) have been developed to detect
      distorted self-reports. However, the validity of these approaches has been
      questioned. In the present study (N = 461), we further examined both IM (assessed
      by the respective subscale of the Balanced Inventory of Desirable Responding
      [BIDR]) and the OCT as measures of self-favoring response biases and their
      associations with honesty-humility. Specifically, we tested the 2 competing
      accounts of IM as a measure of true virtues or a measure of overly positive self
      presentation against each other. Using 2 behavioral paradigms, we corroborated
      recent findings that higher IM scores are associated with higher trait honesty as
      well as with more honest behavior. At the same time, individuals with high IM
      scores also presented themselves overly favorably, as IM accounted for
      discrepancies between hypothetical and actual (incentivized) behavior in a
      dictator game. Thereby, the present results provide direct evidence for the
      notion that the IM subscale of the BIDR confounds trait honesty with response
      bias and thus measures both. In contrast, overclaiming was unrelated to trait
      honesty, all observed behaviors, and self-presentation, indicating that the OCT
      is not a valid measure of self-favoring response bias. (PsycINFO Database Record
      (c) 2018 APA, all rights reserved).

PMID- 30299119
TI  - Primal world beliefs.
AB  - Beck's insight-that beliefs about one's self, future, and environment shape
      behavior-transformed depression treatment. Yet environment beliefs remain
      relatively understudied. We introduce a set of environment beliefs-primal world
      beliefs or primals-that concern the world's overall character (e.g., the world is
      interesting, the world is dangerous). To create a measure, we systematically
      identified candidate primals (e.g., analyzing tweets, historical texts, etc.);
      conducted exploratory factor analysis (N = 930) and two confirmatory factor
      analyses (N = 524; N = 529); examined sequence effects (N = 219) and concurrent
      validity (N = 122); and conducted test-retests over 2 weeks (n = 122), 9 months
      (n = 134), and 19 months (n = 398). The resulting 99-item Primals Inventory (PI
      99) measures 26 primals with three overarching beliefs-Safe, Enticing, and Alive
      (mean alpha = .93)-that typically explain ~55% of the common variance. These
      beliefs were normally distributed; stable (2 weeks, 9 months, and 19 month test
      retest results averaged .88, .75, and .77, respectively); strongly correlated
      with many personality and wellbeing variables (e.g., Safe and optimism, r = .61;
      Enticing and depression, r = -.52; Alive and meaning, r = .54); and explained
      more variance in life satisfaction, transcendent experience, trust, and gratitude
      than the BIG 5 (3%, 3%, 6%, and 12% more variance, respectively). In sum, the PI
      99 showed strong psychometric characteristics, primals plausibly shape many
      personality and wellbeing variables, and a broad research effort examining these
      relationships is warranted. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30299121
TI  - A readability analysis of online mental health resources.
AB  - Analyzing the reading grade level of online mental health information is an
      important first step in ensuring that information is largely accessible by the
      general public, so as not to perpetuate existing health disparities across
      socioeconomic groups. The present study systematically examined grade-level
      readability of mental health information related to various psychiatric
      diagnoses, obtained from 6 highly utilized mental health websites, using a
      generalized estimating equations approach. Results suggest that, in general, the
      readability of mental health information is largely well above the 6th-to-8th
      grade level recommended by several national health organizations, including the
      CDC and NIH (Kutner, Greenberg, Jin, & Paulsen, 2006; National Institutes of
      Health, 2001, 2017), with reading-grade-level estimates from the model ranging
      from 5.62 to 17.9. Further efforts are required to ensure that writers of online
      health information do not exacerbate existing health disparities by ignoring
      these guidelines. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299122
TI  - Community mental health center staff attitudes about employment for persons with
      serious mental illness.
AB  - OBJECTIVE: To measure community mental health agency staff attitudes about
      employment for persons with serious mental illness. METHODS: An online survey was
      developed and sent to 2,218 staff at 4 community mental health centers (CMHC) in
      1 New England state. The survey collected quantitative and qualitative data about
      staff attitudes about employment for persons with serious mental illness.
      Descriptive statistics and qualitative results are provided. Results from
      analysis of variance are provided as well, assessing differences in staff views
      by staff characteristics. RESULTS: A mix of clinical and administrative staff
      participated in the survey (N = 221). Staff views on the benefits of work, the
      ability of clients to handle the demands of the worker role, and client
      motivation to work were mixed. Staff with higher levels of education held
      significantly more supportive views than those with less education. CONCLUSIONS
      AND IMPLICATIONS FOR PRACTICE: CMHC staff need to consistently convey supportive
      attitudes about employment to their clients. (PsycINFO Database Record (c) 2018
      APA, all rights reserved).

PMID- 30299120
TI  - Association between fruit and vegetable intake and symptoms of mental health
      conditions in Mexican Americans.
AB  - OBJECTIVE: No studies so far have shown the effect of fruit and vegetable intake
      on mental disorders in Mexican Americans, for whom mental illness is an important
      health issue. This study measured the association of fruit and vegetable intake
      with the symptoms of cognitive impairment, the indication of increased risk of
      dementia, anxiety, and depression in Mexican Americans. METHOD: Participants were
      drawn from the Cameron County Hispanic Cohort (N = 3,943), a randomly selected
      Mexican American cohort in Texas on the United States-Mexico border. Consumption
      of fruit and vegetables and symptoms of four mental disorders were assessed using
      reliable and validated instruments. RESULTS: Among 2,702 participants (mean age =
      50 years, 34% male) with available data, 213 had cognitive impairment, 61 had the
      indication of increased risk of dementia, 626 had depression, 196 had anxiety,
      and 787 (29.13%) had mental disorders (i.e., any symptoms of the above four
      disorders). Participants who met recommendations of 5 or more servings of fruits
      and vegetables per day were less likely to have anxiety (OR = 0.22, 95% CI [0.08,
      0.65], cognitive impairment (OR = 0.16, 95% CI [0.05, 0.46]), and indication of
      increased risk of dementia (OR = 0.16, 95% CI [0.03, 0.86]) compared with those
      who did not meet recommendations, after adjusting for covariates. Every portion
      increment of total fruit and vegetable intake was significantly associated with
      the reduced odds of mental disorders by 11% and the odds of cognitive impairment
      by 32%, with the adjustment of other covariates. No significant associations were
      found between fruit and vegetable intake and depression. CONCLUSION: Fruit and
      vegetable intake was inversely associated with symptoms of cognitive impairment,
      the indication of increased risk of dementia, and anxiety in Mexican Americans.
      Improving consumption of fruit and vegetables may be a convenient target for
      mental disorder-symptoms prevention and control among Mexican Americans,
      independent of other factors. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30299123
TI  - A qualitative study of racial minority single mothers' work experiences.
AB  - There are approximately 12 million single parent-headed families in the United
      States (U.S.), 80% of which are headed by single mothers (United States Census
      Bureau, 2017). Research suggests that single mothers experience more vocational
      difficulties than married or partnered mothers (Weitoft, Haglund, & Rosen, 2000),
      especially working single mothers. This study explored the work experiences of
      racial minority working single mothers at lower-middle income level using a
      consensual qualitative research method (Hill et al., 2005). Six primary domains
      emerged from the data: (a) job/education decision-making, (b) challenges, (c)
      characteristics of self, (d) resources, (e) coping, and (f) suggestions. We
      present the practical implications of the study to increase vocational mobility,
      inform practitioners, and promote greater overall wellness for this marginalized
      group at various system levels. Suggestions for future research with racial
      minority working single mothers and limitations of the current study are
      discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299124
TI  - Secrets in psychotherapy: For better or worse?
AB  - We investigated how concealment and disclosure of secrets, two related but
      distinct processes, unfolded over the course of open-ended therapy for 39 clients
      and 9 therapists, using hierarchical linear modeling to identify longitudinal
      patterns and investigate relationships with working alliance and session quality.
      Results indicated that over the course of therapy, 85% of clients disclosed at
      least one secret and 41% concealed at least one secret, with 18% of sessions
      including a disclosure and 4% of sessions including concealment. Over time,
      clients were less likely to disclose secrets, and the secrets they chose to
      conceal were rated as less significant. Clients rated the working alliance lower
      after sessions when they disclosed secrets versus when they did not disclose,
      although the working alliance was not rated as poorly when the disclosed secrets
      were viewed as significant. Clients rated session quality higher after sessions
      when they disclosed secrets versus when they did not disclose, particularly when
      they disclosed preoccupying secrets. Clients tended to feel neutral or positive
      about their disclosures. Implications for practice and research are discussed.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299125
TI  - Can auditory objects be subitized?
AB  - In vision, humans have the ability to mentally "tag" approximately 4 objects,
      allowing us to monitor, attend, and interact with them. As a consequence, we can
      rapidly and accurately enumerate up to 4 objects-a process known as subitizing.
      Here, we investigate whether a similar ability exists for tagging auditory
      stimuli and find that only 2 or 3 auditory stimuli can be enumerated with high
      accuracy. We assess whether this high accuracy indicates the existence of an
      auditory subitizing mechanism, and if it is influenced by factors known to
      influence visual subitizing. On the basis of accuracy, Experiments 1 and 2 reveal
      a potential auditory subitizing mechanism only when stimuli are spatially
      separated, as is the case for visual subitizing. Experiment 3 failed to show any
      evidence of auditory subitizing when objects were separated in time, rather than
      space. All three experiments provide only limited evidence for an age-related
      decline in auditory enumeration of small numbers of objects. This suggests that
      poor auditory tagging does not contribute significantly to older adults'
      difficulties in multitalker conversations. We hypothesize that although auditory
      subitizing might occur, it is restricted to approximately 2 spatially separated
      objects due to the difficulty of parsing the auditory scene into its constituent
      parts. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299126
TI  - Pimping inhibition: Anodal tDCS enhances stop-signal reaction time.
AB  - The stop-signal task (SST) is assumed to reliably measure response inhibition;
      specifically, in this task participants sometimes have to withhold a response
      according to the onset of a sudden cue. The response-stopping process is
      estimated by a stochastic model that delivers the stop-signal reaction time
      (SSRT; Verbruggen & Logan, 2009), that is, the latency to inhibit prepotent
      responses. The right dorsolateral prefrontal cortex (rDLPFC) plays a key role in
      goal directed cognitive control in general and particularly an increased
      activation has been associated with better SST performance (that is with shorter
      SSRT). We stimulated the rDLPFC in a prepost design via transcranial DC
      stimulation (tDCS). A 9 cm2 anode was always positioned over the rDLPFC while the
      35 cm2 cathode was placed over the left deltoid. We contrasted an anodal
      stimulation condition (that is assumed to enhance neural processing) with sham
      stimulation and expected an increase in inhibitory functions after anodal tDCS,
      as evidenced by a decrease in SSRT. In a sample of N = 56 healthy adults, we
      found a significant Time * tDCS-Condition interaction in the expected direction.
      Control analysis confirmed that the statistically significant decrease in SSRT
      after anodal tDCS was not due to generally faster reaction times. These results
      confirm the role of the rDLPFC for cognitive inhibition processes and further
      suggest that inhibition is not a fixed resource but depends on the current state
      of the PFC. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299127
TI  - Skin color and academic achievement in young, Latino children: Impacts across
      gender and ethnic group.
AB  - OBJECTIVES: The present study investigates the association between skin color and
      academic achievement in young Latino students. METHOD: Data were drawn from a
      longitudinal study of the early development of Latino children that took place in
      24 public elementary schools in New York City. Students included in the present
      analyses (N = 750) were 4 and 5 years old when they were enrolled (baseline) and
      were followed through the end of first grade. Structural equation models and
      bootstrapping mediation tests were conducted to examine the effects of skin color
      on academic achievement at the end of first grade, partially mediated by academic
      and social emotional domains of school readiness in prekindergarten or
      kindergarten. This study considered the intersectionality of ethnicity and gender
      in the models. RESULTS: The findings showed that for Dominican-origin boys, being
      "collectively black" was indirectly associated with lower academic achievement in
      first grade, mediated by lower teacher-rated adaptive behavior in prekindergarten
      or kindergarten. CONCLUSIONS: Discussion focuses on the need for educational
      policies and practices to be conscious of phenotypicality bias. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30299128
TI  - Focusing on what matters: Restructuring the presentation of Bayesian reasoning
      problems.
AB  - We propose that a mismatch in problem presentation and question structures may
      promote errors on Bayesian reasoning problems. In this task, people determine the
      likelihood that a positive test actually indicates the presence of a condition.
      Research has shown that people routinely fail to correctly identify this positive
      predictive value (PPV). We point out that the typical problem structure is likely
      to confuse reasoners by focusing on the incorrect reference class for answering
      this diagnostic question; instead, providing the anchor needed to address the
      diagnostic question about sensitivity (SEN). Results of two experiments are
      described in which participants answer diagnostic questions using problems
      presented with congruent or incongruent reference classes. Aligning reference
      classes eases both representational and computational difficulties, increasing
      the proportion who were consistently accurate to an unprecedented 93% on PPV
      questions, and 69% on SEN questions. Analysis of response components from
      incongruent problems indicated that many errors reflect difficulties in
      identifying and applying appropriate values from the problem, which are
      prerequisite processes that contribute to computational errors. We conclude with
      a discussion of the need, especially in applied settings and on initial exposure,
      to adopt problem presentations to guide, rather than confuse, the organization
      and use of diagnostic information. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30299129
TI  - Assessing the transfer of interruption resumption skill to novel tasks.
AB  - Interruption interference refers to significant performance decreases that follow
      task interruption. Evidence has suggested that practicing interruption resumption
      reduces interruption interference as measured by the time required to resume the
      interrupted task. However, evidence has also indicated that interruption practice
      only improves resumption for the practiced pair of primary and interrupting
      tasks. If this is true, then there is little applied benefit in interruption
      training, because the training would be unlikely to transfer beyond the training
      environment. In the current studies, a transfer paradigm was utilized to
      determine whether interruption resumption skill practiced within a task-pair
      transfers to a novel task-pair. The results of Experiments 1A and 1B provide
      evidence that interruption resumption skill transfers to another primary task
      when the interrupting task is either held constant or varies. Experiment 2
      manipulated the primary tasks to minimize the ability to reconstruct the next
      step in problem solving. When minimizing reconstruction, resumption skill that
      transfers is likely the ability to successfully retrieve the next planned action
      that was suspended when interrupted. The results support the conclusion that
      resumption skill does transfer and, therefore, opens up additional research
      avenues with applications to minimizing interruption interference. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30299130
TI  - Does semantic long-term memory impact refreshing in verbal working memory?
AB  - Attentional refreshing allows the maintenance of information in working memory
      and has received growing interest in recent years. However, it is still ill
      defined and several proposals have been put forward to account for its
      functioning. Among them, some proposals suggest that refreshing relies on the
      retrieval of knowledge from semantic long-term memory. To examine such a
      proposal, the present study examined the impact on refreshing of two effects
      known to affect the retrieval from semantic long-term memory: word frequency and
      lexicality. In working memory span tasks, participants had to maintain memoranda
      varying in either frequency, or lexicality while performing concurrent tasks. By
      examining recall performance in complex span tasks and response times for the
      concurrent task in Brown-Peterson tasks, the present study provided evidence that
      long-term memory effects (a) affected recall without interacting with
      manipulation of refreshing and (b) did not affect refreshing speed. These
      findings challenge the idea that refreshing acts through the retrieval of
      knowledge from semantic long-term memory. Different WM models are discussed to
      account for these findings. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30299131
TI  - Properties of familiar face representations: Only contrast positive faces contain
      all information necessary for efficient recognition.
AB  - It is difficult to recognize the identity of a face presented in negative
      contrast. This difficulty, however, is substantially reduced when only the eye
      region is contrast positive in an otherwise negative face image, and recognition
      of these so-called contrast chimeras approaches performance with full positive
      faces. This apparently similar accuracy has led researchers to suggest that
      familiar face representations are built around the eye region. The present study
      used the N250r, an event-related brain potential correlate of repetition priming,
      to examine whether chimera recognition is similarly efficient as positive face
      recognition. In a series of 3 experiments, we found a clear N250r for positive
      but reduced or even absent repetition effects for negative and chimera faces.
      This finding held true independent of whether the same basic pictures of familiar
      faces were used as prime and target stimuli (Experiment 1) or not (Experiments 2
      and 3). Similar results were also obtained independent of whether positive,
      negative or chimera primes preceded full positive targets (Experiments 1 and 2)
      or targets in the same respective contrast format (Experiment 3). These results
      indicate that only positive faces contain all information necessary for optimal
      face recognition and that even though contrast chimeras are recognized highly
      accurately, the underlying processes work less efficiently as compared with
      normal face recognition. We conclude that familiar face representations are not
      built around the eyes but comprise detailed information from other regions of the
      face. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299132
TI  - Psychological and relational health profiles of soldiers in committed romantic
      relationships.
AB  - The present study explored the heterogeneity of military service members'
      psychological and relational functioning using a sample of 7,866 soldiers in
      committed romantic relationships from the Army Study to Assess Risk and
      Resilience in Service members (Army STARRS). A latent profile analysis was
      conducted to identify and predict unique clusters of soldiers' relative
      psychological (i.e., posttraumatic stress disorder, depression, and anxiety
      symptom severity) and relational (i.e., relationship happiness, how often their
      relationship was going well, how often they confided in their partner, how often
      they considered or discussed ending their relationship, relational insecurity,
      and relational turbulence) functioning. Results revealed 4 distinct classes of
      comparative psychological and relational health: hardy soldiers and healthy
      relaters (70.2%), stressed soldiers but healthy relaters (13.1%), hardy soldiers
      but strained relaters (12.7%), and stressed soldiers and strained relaters
      (4.0%). Class descriptions, as well as implications for theory and clinical
      practice are reviewed. Notably, 7 out of 10 soldiers in this nationally
      representative sample reported little to no psychological or relational distress.
      These findings invite more adaptive narratives of service member resilience and a
      more nuanced conceptualization of gradations in psychological and relational
      functioning. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299133
TI  - A two-way street: Mothers' and adolescent daughters' depression and PTSD symptoms
      jointly predict dyadic behaviors.
AB  - Dyadic interactions may be affected by the mental health of either partner;
      however, both partners' symptoms are typically not considered simultaneously in
      observational studies of parent-child relationships. Using the actor-partner
      interdependence model (APIM), we examine how depression and posttraumatic stress
      disorder (PTSD) symptoms in mothers and adolescent daughters predict their own
      and each other's relational behaviors (warmth, hostility, communication) during
      interactions, and whether partners' relational behaviors predict changes in
      symptoms 1 month later. Participants include 150 mother (mean age = 41.6) and
      daughter (mean age = 15.1) dyads from diverse (57% Latina; 23% Black, 20% White),
      low-income families. Mothers and daughters reported on their symptoms and
      participated in a videotaped interaction task. A subset completed a follow-up
      interview 1 month later. For both depression and PTSD, mothers' and daughters'
      symptoms predicted their own relational behaviors (actor effects). In contrast,
      partner effects varied by symptom type and family role. Adolescents' depressive
      symptoms predicted how their mothers acted toward them, beyond maternal symptoms
      (an additive partner effect); the converse was not true. Mother and daughter PTSD
      symptoms interactively predicted daughters' relational behaviors (an Actor *
      Partner interaction), with buffering or exacerbating effects based on dyad
      symptom similarity. PTSD symptoms had unique effects beyond depression. In
      longitudinal analysis, mothers' relational behaviors predicted changes in
      adolescents' depressive symptoms, but adolescent behaviors were unrelated to
      subsequent maternal symptoms. Findings suggest that depression and PTSD symptoms
      may affect family relationships differently, and highlight the importance of
      considering both members' symptoms during interactions. Implications for dyadic
      interventions are discussed. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30299134
TI  - Positive parental engagement: Investigating the role of the mother-father
      relationship.
AB  - Promoting positive parental engagement (e.g., reading to the child, practicing
      nursery rhymes with the child, playing with the child) is beneficial for
      children. Previous research has largely been limited to only maternal reports and
      relatively affluent families. The current study longitudinally investigated
      spillover between positive experiences in the mother-father relationship and
      positive parental engagement using an ethnically and economically diverse sample
      of parents. Using data from the Fragile Families and Child Wellbeing Study (N =
      3,780 mother-father dyads)-and guided by family systems theory-we tested a series
      of path analysis models. Positive relationship experiences predicted positive
      parental engagement over time (from child's birth-5 years of age) for both
      mothers and fathers. Furthermore, strength of associations between positive
      relationship experiences and positive parental engagement largely did not differ
      based on family structure, poverty, or race. These findings highlight the
      importance of investigating the mother-father relationship using a family systems
      framework to better understand positive parental engagement. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 30299135
TI  - Associations between father involvement and father-child attachment security:
      Variations based on timing and type of involvement.
AB  - This study examined associations between father involvement and father-child
      attachment security, and whether those associations differed as a function of
      timing (workday and nonworkday) and/or type (accessibility, caregiving, and play)
      of involvement. Eighty father-child dyads participated when children were
      approximately 3 years old. Fathers completed a time diary interview assessing the
      various forms of involvement, and attachment was assessed using the Attachment Q
      Set (Waters, 1995) following 90 min of father-child observation in the home. On
      nonworkdays, father involvement in play predicted greater attachment security and
      involvement in caregiving was marginally associated with greater attachment
      security. On workdays, father involvement in caregiving was related to greater
      attachment security, whereas father involvement in play was related to less
      attachment security. Results were independent of observed paternal sensitivity
      and relevant demographic covariates. Findings highlight the differential impact
      of father involvement for the father-child attachment relationship depending on
      when involvement occurs and what types of activities fathers engage in. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30299137
TI  - Patterns of workplace discrimination across broad categories of disability.
AB  - OBJECTIVE: The aim of this study was twofold: (a) to explore patterns of
      discrimination in relation to broad-basis categories of disability and (b) to
      investigate patterns of discrimination between allegations derived from charging
      parties with sensory impairments versus those with nonsensory impairments. Basis
      categories included physical, behavioral, neurological, and sensory impairments.
      RESEARCH METHOD: Database mining, descriptive analysis, and Pearson's chi-square
      analyses were utilized to compare broad-basis categories. RESULTS: In general,
      regardless of disability type, individuals experience the highest frequency and
      proportion of workplace discrimination in the areas of termination and reasonable
      accommodations. However, there are significant differences in the workplace
      discrimination experiences of the four broader groups. CONCLUSIONS: Noteworthy
      differences exist regarding the experience of workplace discrimination among
      basis categories of disability, especially with respect to sensory impairment.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299136
TI  - Positive factors, pain, and function in adults with multiple sclerosis.
AB  - OBJECTIVE: Much is known about the associations between negative factors and
      adjustment to chronic pain. However, less is known about how positive factors
      (e.g., positive affect [PA], resilience) function in relation to disability and
      mood in individuals with multiple sclerosis (MS). To better understand how
      positive factors contribute to function we sought to determine if (a) PA and/or
      trait resilience moderate the associations between pain intensity and function
      (pain interference, depressive symptoms), and (b) trait resilience concurrently
      mediates the association between PA and function in a sample of individuals with
      MS. METHOD: There were 455 adults with MS who provided data via an ongoing
      survey. RESULTS: Controlling for negative affect, demographic, and disease
      related variables, cross-sectional path analysis revealed the following: PA and
      trait resilience did not moderate the associations between pain intensity and
      pain interference (betaPA = 0.01, p = .86; betaRESILIENCE = 0.04, p = .33), and
      pain intensity and depression (betaPA = 0.01, p = .79; betaRESILIENCE = -0.02, p
      = .60). However, trait resilience significantly mediated the associations between
      PA and both criterion variables (abINTERFERENCE = -0.03, p = .03; abDEPRESSION = 
      0.13, p < .001). CONCLUSIONS: The findings provide preliminary support for the
      conclusion that PA is indirectly related to pain interference and depression via
      resilience, rather than serves as a protective function. The findings are
      consistent with theoretical models suggesting that increases in PA build personal
      resources. Research examining the potential benefits of increasing PA and
      resilience to improve pain outcomes in individuals with MS is warranted.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299138
TI  - Anxiety, depression, and function in individuals with chronic physical
      conditions: A longitudinal analysis.
AB  - OBJECTIVE: This longitudinal study examined the unique relationship between
      anxiety, symptoms (pain intensity, sleep disturbance, fatigue severity), and
      function domains (self-reported cognitive function, physical function,
      satisfaction with social roles) in individuals with chronic physical conditions,
      independent of depressive symptoms. METHOD: Three surveys were mailed on an
      approximately yearly basis to community-dwelling adults with one of four chronic
      physical conditions (spinal cord injury, multiple sclerosis, muscular dystrophy,
      postpoliomyelitis syndrome). The first survey was completed by 1594 individuals
      (T1). Of these, 1380 completed the second survey (T2), and 1272 completed the
      third survey (T3). RESULTS: Mixed growth curve models evidenced significant
      concurrent and longitudinal associations between anxiety and each symptom and
      function domain, independent of depression severity. The largest unique
      association found was between anxiety and self-reported cognitive function;
      inclusion of the measure of anxiety in the model improved model fit substantially
      over depression alone, chi2[2] = 104.40, p < .001. Both anxiety and depression
      exhibited similar effect sizes in their unique relationships with each symptom
      and function domain measure. However, depression was more strongly associated
      with satisfaction with social roles and physical function than was anxiety.
      CONCLUSIONS: The findings showed that anxiety assessed at one point in time
      demonstrated significant and unique associations with concurrent and subsequent
      symptom and function domains. Given that anxiety has been inadequately studied
      (and perhaps evaluated and treated) in rehabilitation populations, the current
      findings suggest that researchers and clinicians should broaden their scope when
      assessing and treating psychological distress to incorporate anxiety and related
      disorders. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299139
TI  - Psychological difficulties and parental well-being in children with
      musculoskeletal problems in the 2011/2012 National Survey of Children's Health.
AB  - OBJECTIVE: This study compared children with and without current musculoskeletal
      (MSK) problems on key indices of child psychological adjustment and parental well
      being. RESEARCH METHOD: Prevalence estimates of psychological problems were
      compared for children ages 2-17 years with and without current MSK problems in
      the 2011/2012 National Survey of Children's Health. Multivariate logistic
      regression analyses examined the effects of MSK problem severity on the risk of
      psychological concerns. RESULTS: Population level differences in prevalence
      estimates were observed in psychological difficulties. Children with MSK problems
      were disproportionally affected by anxiety problems, depression,
      behavioral/conduct problems, and ADHD compared to children without MSK problems.
      Compared to children with mild MSK problems, children with severe MSK problems
      were 2.74 times more likely to have anxiety problems (95% CI [1.35, 2.86], p <
      .05). No other significant differences were found among children with mild,
      moderate, or severe MSK problems. Regarding parental well-being, compared to
      children without MSK problems, children with MSK problems were more likely to
      have mothers and fathers who often experience parenting stress/aggravation and
      have poor physical and mental health. CONCLUSIONS: Children with MSK problems are
      vulnerable to psychological difficulties that can affect their learning,
      development, and quality of life. Psychological screening and ensuring that these
      children receive effective mental health treatments should be a priority in
      pediatric health care settings. Consideration of parental physical and mental
      health is recommended in the assessment and treatment of children with MSK
      problems. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299140
TI  - Sex/gender disparities in health outcomes of individuals with long-term disabling
      conditions.
AB  - BACKGROUND: Women with disabling conditions experience health disparities
      relative to nondisabled women, but few studies have compared women and men with
      disabling conditions. OBJECTIVES: To investigate gender differences in physical
      functioning and emotional health among individuals with long-term disabling
      conditions, that is, neuromuscular disease, multiple sclerosis, postpolio
      syndrome, or spinal cord injury. METHOD: From a mailed survey of 1,862 adults
      with long-term disabling conditions, we used the 12-item Patient-Reported
      Outcomes Measurement Information System (PROMIS) physical functioning to assess
      physical limitations in activities and Patient Health Questionnaire-9 (PHQ-9) for
      emotional health and severity of secondary conditions (rated 0-10). Least square
      means models were used to estimate marginal mean PHQ-9 scores and severity of
      secondary conditions by age and sex adjusted for diagnosis. Generalized linear
      models were performed to determine the association between sex/gender and PROMIS
      physical function t score, controlling for age and diagnostic group with
      potential Age * Sex interaction. RESULTS: Women reported more fatigue than men
      (5.48 +/- .08 vs. 5.13 +/- .11, p = .01) and more pain (3.99 +/- .08 vs. 3.67 +/-
      .11, p = .03). Women aged 45-54 had higher average PHQ-9 scores than men aged 45
      54 (M = 8.05, SE = .33 vs. M = 6.35, SE = .42, p < .007) adjusted for diagnosis.
      Younger women had higher physical functioning than younger men while older women
      had lower physical functioning than older men adjusted for diagnostic group (p =
      .0003 for the interaction term). CONCLUSION: Middle-aged and older women with
      long-term disabling conditions experience considerable health disparities in
      physical functioning and emotional health compared with middle-aged and older men
      with similar conditions. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30299141
TI  - Wise interventions: Psychological remedies for social and personal problems.
AB  - Long-standing social problems such as poor achievement, personal and intergroup
      conflict, bad health, and unhappiness can seem like permanent features of the
      social landscape. We describe an approach to such problems rooted in basic theory
      and research in social psychology. This approach emphasizes subjective meaning
      making-working hypotheses people draw about themselves, other people, and social
      situations; how deleterious meanings can arise from social and cultural contexts;
      how interventions to change meanings can help people flourish; and how initial
      change can become embedded to alter the course of people's lives. We further
      describe how this approach relates to and complements other prominent approaches
      to social reform, which emphasize not subjective meaning-making but objective
      change in situations or in the habits and skills of individuals. In so doing, we
      provide a comprehensive theoretical review and organization of a psychologically
      informed approach to social problems, one that encompasses a wide-range of
      interventions and applies to diverse problem areas. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 30299142
TI  - Modulation of attention and action in the medial prefrontal cortex of rats.
AB  - Theories of functioning in the medial prefrontal cortex are distinct across
      appetitively and aversively motivated procedures. In the appetitive domain, it is
      argued that the medial prefrontal cortex is important for producing adaptive
      behavior when circumstances change. This view advocates a role for this region in
      using higher-order information to bias performance appropriate to that
      circumstance. Conversely, literature born out of aversive studies has led to the
      theory that the prelimbic region of the medial prefrontal cortex is necessary for
      the expression of conditioned fear, whereas the infralimbic region is necessary
      for a decrease in responding following extinction. Here, the argument is that
      these regions are primed to increase or decrease fear responses and that this
      tendency is gated by subcortical inputs. However, we believe the data from
      aversive studies can be explained by a supraordinate role for the medial
      prefrontal cortex in behavioral flexibility, in line with the appetitive
      literature. Using a dichotomy between the voluntary control of behavior and the
      execution of well-trained responses, we attempt to reconcile these theories. We
      argue that the prelimbic region exerts voluntary control over behavior via top
      down modulation of stimulus-response pathways according to task demands,
      contextual cues, and how well a stimulus predicts an outcome. Conversely, the
      infralimbic region promotes responding based on the strength of stimulus-response
      pathways determined by experience with reinforced contingencies. This system
      resolves the tension between executing voluntary actions sensitive to recent
      changes in contingencies, and responses that reflect the animal's experience
      across the long run. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30299143
TI  - The construct-behavior gap and the description-experience gap: Comment on
      Regenwetter and Robinson (2017).
AB  - Regenwetter and Robinson (2017) discuss a challenging construct-behavior gap in
      psychological research. It can emerge when testing hypotheses that pertain to a
      theoretical construct (e.g., preferences) on the basis of observed behavior
      (e.g., actual choices). The problem is that the different heuristic methods that
      are sometimes used to link overt choices to covert preferences may ignore
      heterogeneity between and within individuals, rendering inferences drawn from
      choices to preferences invalid. Regenwetter and Robinson's remedy is to make
      heterogeneity an explicit part of the theory. They illustrate the problem and a
      remedy to it with the description-experience gap (D-E gap), the systematic gap in
      choices based on described versus 'experienced' probabilities. We welcome their
      sophisticated reanalysis of some early data sets, which, by taking heterogeneity
      into account, finds strong evidence for a D-E gap in probability weighting. Yet
      we see three issues with the remedy, which we likewise highlight using the D-E
      gap. First, the D-E gap cannot be reduced solely to probability weighting but
      rather unfolds across several different psychological constructs suggesting that
      part of the construct-behavior gap may stem from trying to reduce
      multidimensional behavior to a single construct. Second, the authors' modeling of
      heterogeneity leaves aside the heterogeneity of people's sampled experience in
      decisions from experience, which highlights the importance of also considering
      the potential causes of heterogeneity. Third, we identify potential sources of
      heterogeneity in choice behavior that go beyond probabilistic responses and
      preferences and advocate for a pluralistic approach to modeling it. Last but not
      least, we emphasize that, notwithstanding the importance of rigor and logical
      coherence in scientific theories, simplifications and (false) generalizations are
      indispensable in the pursuit of scientific knowledge. (PsycINFO Database Record
      (c) 2018 APA, all rights reserved).

PMID- 30299144
TI  - "Fast" versus "slow" word integration of visual and olfactory objects: EEG
      biomarkers of decision speed variability.
AB  - In psychological experiments, behavioral speed varies across trials, and this
      variation is often associated with corresponding fluctuations in cortical
      activity. Little is known about such cortical variations in semantic priming
      tasks where target words are matched with preceding sensory object cues. Here,
      two visually presented target words ("pear" and "lilac") were repeatedly cued by
      corresponding odors or pictures, and the participants were to indicate matching
      or nonmatching combinations. Data were split in behaviorally "fast" versus "slow"
      trials. We hypothesized that slow trials would be associated with higher
      prestimulus alpha activity and reduced ERP amplitudes, and that response-time
      differences between odor-cued and picture-cued trials would be especially large
      in slow behavioral trials. Results confirmed that slow trials showed increased
      alpha-band activity prior to word target onset, as well as amplitude decreases in
      the sensory P1 and semantic N400 components. However, no interactions between cue
      modality and processing speed were observed. Instead, odor-cue integration
      responses were uniquely delayed on incongruent trials, a novel behavioral effect
      that was not observed in EEG measures. The results show that semantic integration
      speed is reflected in cortical activity before and during stimulus processing.
      Behavioral interactions with cue modality did not correspond to observed cortical
      activity changes, perhaps because olfactory circuits are not readily observed in
      scalp-recorded EEG. We conclude that combining behavioral speed variability and
      cortical EEG measures is useful in understanding the fluctuating nature of
      cognitive processing sequences. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30299145
TI  - Context-dependent reinstatement of an extinguished operant response in
      preweanling rats.
AB  - It is frequently assumed that infants are impaired in contextual memory and
      consequently, in recovery from extinction, a phenomenon considered to be context
      dependent. However, the evidence in the field is far from consistent with this
      interpretation, since several studies have shown context-dependent extinction in
      infant rats using a variety of procedures and behavioral measures. This
      discussion has primarily been based on studies using Pavlovian conditioning
      tasks. Three experiments were conducted to study reinstatement of an extinguished
      operant response and additionally to evaluate the context dependence of such an
      effect. Preweanling rats were trained on postnatal days (PDs) 16 and 17 to
      acquire an appetitive operant response using chocolate milk as reinforcer. At
      PD18 the operant response was extinguished and at PD19 animals received a
      reminder in the same (Experiment 1 and 2) or in a different context than the one
      used during the extinction phase (Experiment 3). Infant rats showed recovery from
      extinction after a reminder treatment (Experiments 2 and 3). This effect was
      dependent on the context in which the reminder was delivered (Experiment 3). Our
      results indicate that infant rats can recover an extinguished operant response by
      means of a reminder treatment in a context-dependent way, highlighting the
      importance of the context for modulating learning processes during infancy.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299146
TI  - Blockade of dopamine D1 receptors, but not D2 receptors, decreases motivation in
      a novel effort-discounting paradigm in common marmosets.
AB  - Effort-based decision-making paradigms have recently been used to measure
      motivation in healthy subjects and patients with neuropsychiatric disorders. In
      the present study, we developed a novel effort-discounting paradigm using a touch
      panel system in common marmosets. Marmosets were trained to choose between a low
      reward (a piece of cake) requiring low-effort (one touch response) versus high
      reward (three pieces of cake) requiring one of three different effort levels
      (one, two, or four touch responses). Because the number of trials per session was
      kept constant, the selection of the high-reward choice was always the optimal
      strategy to receive the maximum number of rewards. Marmosets' high-reward rates
      were reduced as the physical effort requirement was increased, when they were
      tested using effort discounting in either ascending or descending order of effort
      intensity. It indicates that marmosets' decisions could be attributable to cost
      benefit evaluation, but not to their fatigue or satisfaction with the reward
      during the progression of the paradigm. The high dose of dopamine D1 receptor
      antagonist SCH-39166 (0.03 mg/kg) reduced the high-reward choice rate, only when
      more effort was required to obtain the high-reward than the low-reward. On the
      other hand, the D2 receptor antagonist raclopride (0.01 and 0.03 mg/kg)
      unexpectedly did not affect the high-reward choice rate, but the high dose did
      increase omission rate. Our finding suggests that dopamine D1 receptor signaling
      may play a more important role in effort-based decision making than D2 receptor
      signaling in marmosets. Our novel behavioral paradigm would be useful in
      translational research focused on motivational deficits. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 30299147
TI  - Reversal learning impairments in the maternal immune activation rat model of
      schizophrenia.
AB  - One of the cognitive symptoms observed in schizophrenia is decreased flexibility
      in several tasks, including reversal learning. Reversal learning has previously
      been tested in rats following maternal immune activation (MIA), a risk factor for
      schizophrenia, with varying results. Whereas some previous studies have shown
      that MIA rats are slower to learn a reversal, others have reported more rapid
      learning compared with controls. Several of these latter studies have, however,
      used a T-maze task with aversive, negative reinforcement as a motivating factor.
      Because most human studies use positive reinforcement in reversal tasks, here we
      tested whether reinforcement valence might be a critical factor. We ran male MIA
      and control rats in a T-maze reversal procedure that was very similar to previous
      studies except that positive, appetitive reinforcement was used for motivation.
      The results showed that MIA animals performed similarly to controls during
      training, but in contrast to the previous, aversively motivated T-maze studies,
      slower reversal learning was observed. These results show that MIA animals are
      impaired in reversal learning under conditions of positive reinforcement,
      consistent with the effects observed in individuals with schizophrenia. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30299148
TI  - Sensorimotor representation and functional motor changes following short-term arm
      immobilization.
AB  - Limb immobilization paradigms are increasingly used to investigate changes in
      brain plasticity and support potential rehabilitation techniques that might help
      counteract motor impairments. Yet, it remains unclear how unilateral arm
      immobilization may influence the sensorimotor representation and functional
      output for both arms. Using a randomized crossover design, 14 participants
      underwent a baseline test, followed by two experimental conditions separated by 1
      week: a right (dominant) arm immobilization phase over a period of 8 hr and a no
      immobilization (or control) phase also lasting 8 hr. Before and after each
      condition, participants were tested on a hand laterality judgment task to assess
      changes in sensorimotor representation of the hands, followed by an out-and-back
      reaching motor task measuring changes in spatiotemporal components of motor
      actions. Data from the hand laterality judgment task revealed that participants
      were faster at identifying right-hand pictures after the control phase, but such
      improvement was not observed after the immobilization phase, with no effect of
      immobilization for pictures depicting the overused left hand. Results from the
      reaching motor task revealed that the right-arm movement planning component was
      altered after immobilization, whereas there was no effect for the overused left
      arm. Altogether, these findings demonstrate that an 8-hr period of unilateral
      immobilization affects sensorimotor representation and functions of the
      corresponding limb, but not of the overused, nonimmobilized hand. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30299149
TI  - The relationship between on-campus service utilization and common mental health
      concerns in undergraduate college students.
AB  - Little research exists into the trends associated with on-campus service
      utilization for mental health concerns of college students. Rates of broad
      service utilization exist, but no published study has examined the direct
      relationship between a range of common mental health symptoms and on-campus
      service utilization. The aims of the present study are to explore (1) which
      common mental health concerns are associated with specific on-campus service
      utilization in undergraduate students and (2) whether endorsement of more mental
      health concerns will predict a higher number of services utilized. Data were
      utilized from 3,734 undergraduates at a large (more than 20,000 undergraduates),
      urban university (Mage = 19.94 years, SD = 0.55 years; female = 66%). Four on
      campus services (University Counseling Services, University Health Services, The
      Wellness Resource Center, and Disability Support Services) were regressed onto
      mental health concerns associated with symptoms of three disorders (anxiety,
      depression, alcohol use disorder [AUD]) and two mental health risk factors
      (stressful life events [SLEs], antisocial behaviors [ASBs]). AUD symptoms
      predicted the most overall and specific service utilization, followed by
      depression symptoms and SLEs. Anxiety symptoms and ASBs were not significant
      predictors when combined with other variables. This is the first study to
      investigate trends specific to on-campus college student service utilization.
      Findings will be helpful to mental health professionals on similar college
      campuses by providing insight into programming and outreach initiatives for these
      or related services. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30299150
TI  - Psychometric properties of a brief measure of posttraumatic stress disorder
      related impairment: The Brief Inventory of Psychosocial Functioning.
AB  - This study validated the Brief Inventory of Psychosocial Functioning (B-IPF), an
      abridged version of the 80-item Inventory of Psychosocial Functioning (IPF; Bovin
      et al., 2018). The B-IPF-a 7-item self-report questionnaire that assesses
      posttraumatic stress disorder (PTSD)-related psychosocial functional impairment
      was developed for use in settings in which the full IPF would be too time
      intensive to administer. In this study, we examined the psychometric properties
      of the B-IPF among a sample of 362 veterans recruited from 2 Veterans Affairs
      hospitals. The B-IPF demonstrated high internal consistency (Cronbach's alpha =
      .84) and adequate test-retest reliability (r = .65, p < .001). The B-IPF was
      strongly correlated with the IPF (r = .71, p < .01) and had higher correlations
      with measures of mental health impairment and quality of life (all rs > ?.50?;
      all ps < .001) than with a measure of physical health impairment (i.e., the
      Physical Component Summary; r = -.34; p < .001), which demonstrated strong
      construct validity. In addition, the B-IPF displayed strong criterion-related
      validity, with higher correlations with a PTSD symptom measure, (r = .63, p <
      .05), and measures of other internalizing disorders (all rs > .44; all ps < .05)
      and a lower correlation with a measure of an externalizing disorder (r = .14; p <
      .05). These results indicate that the B-IPF is a reliable and valid instrument
      for assessing PTSD-related impairment. The strong psychometric properties of the
      instrument, in addition to its length, make it ideal for settings in which time
      is a factor. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299151
TI  - Mental health utilization among veterans at risk for suicide: Data from a post
      deployment clinic.
AB  - The current study aim was to examine mental health characteristics in a sample of
      returning OEF/OIF/OND veterans initially enrolling in Department of Veterans
      Affairs (VA) health care (N = 1,307), with a particular focus on a subgroup
      considered at risk for suicide (N = 445). Methods included examination of mental
      health screening measures and clinical interview data from a VA postdeployment
      clinic. Half of the sample met criteria for a mental health disorder, whereas 10%
      reported current suicidal or death ideation (e.g., thoughts of being better off
      dead or hurting oneself in some way) and 6% reported a history of suicide
      attempt. Sixty-eight percent of the at-risk subgroup accepted a referral for
      mental health treatment and a promising majority (78%) of those individuals
      attended their initial specialty mental health visit. At-risk veterans who
      accepted mental health referral were more likely to report current suicidal/death
      ideation; they were also more likely to have a diagnosis of a depressive
      disorder, anxiety disorder, or posttraumatic stress disorder. Factors associated
      with mental health appointment attendance included older age, being enrolled in
      college, and more years of military service. Results highlight the importance of
      early screening and referral to appropriate mental health follow-up. Implications
      for clinical practice and increasing engagement in VA mental health services
      among veterans at risk for suicide are discussed. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 30299152
TI  - Aging and attention: Meaningfulness may be more important than valence.
AB  - Studies on socioemotional selectivity theory have found that compared with
      younger adults, older adults are more likely to (a) prefer to interact with
      emotionally close social partners and (b) show preferential cognitive processing
      of positive relative to negative stimuli. To integrate these 2 lines of findings,
      this study examined attention toward emotional (positive and negative) facial
      expressions of experimentally manipulated emotionally close versus nonclose
      targets among younger and older adults. Compared with younger adults, older
      adults gazed more at facial expressions of emotionally close than nonclose
      targets, regardless of valence. This age difference occurred to a greater extent
      among those who endorsed eudaimonic goals more. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 30299153
TI  - Age-related differences in levels and dynamics of workplace affect.
AB  - Affective experiences at work are a key contributing factor to long-term job
      related well-being and effectiveness, yet may systematically change as workers
      get older. Given the central role of affect in work settings, it is important to
      obtain a thorough understanding of older workers' strengths and vulnerabilities
      in affective functioning. This paper's goal was to comprehensively study age
      differences in mean levels and dynamics of affect (affect stability, occurrence
      of positive and negative daily work events, and affective reactivity) and to link
      these with perceptions of global occupational well-being and effectiveness. In
      three diary studies, employees of different occupational and cultural backgrounds
      (Hong Kong Chinese managerial employees, German hospital employees, German office
      workers) reported daily affective work events and affect across multiple
      workdays. Higher age was associated with more positive and less negative affect
      (Study 1), more frequent positive daily work events (Study 2 and 3), and lower
      variability of negative affect (Study 1 and 2). Age was unrelated to frequency of
      negative work events and positive event reactivity (all studies). There were
      mixed age differences in negative event reactivity (lower reactivity in Study 1
      and on subtypes of affect in Study 2, but higher worry in Study 3). Several of
      the indicators of affective experience emerged as mediators of positive age
      differences in work engagement and self-rated task performance. Overall, with one
      exception, results point at maintenance or improvement of workers' affective
      functioning with age. Through improved affective functioning, older workers
      likely contribute to organizational effectiveness. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 30299154
TI  - Valuing excitement makes people look forward to old age less and dread it more.
AB  - Previous research has shown that American culture places a premium on excitement,
      enthusiasm, and other high-arousal positive states (HAP) compared with various
      East Asian cultures. In two studies, we tested the prediction that valuing HAP
      would be associated with less positive personal views of old age (i.e., fewer
      things people looked forward to and more things they dreaded about old age) in
      samples of European American, Chinese American, and Hong Kong Chinese younger,
      middle-aged, and older adults. In Study 1 (N = 849), participants rated how much
      they ideally wanted to feel HAP during a typical week and described their
      personal views of old age. As predicted, European American middle and older
      adults valued HAP more than did their Chinese American and Hong Kong Chinese
      peers, and these differences in ideal HAP were related to less positive personal
      views of old age. In Study 2 (N = 164), we experimentally manipulated how much
      individuals valued HAP and then assessed their personal views of old age: Across
      cultures, participants in the "value HAP" condition had less positive personal
      views of old age than did those in the control condition. These effects did not
      emerge for societal views of old age (i.e., what people associated with "someone"
      old vs. young). Together, these findings suggest that people's personal views of
      their own old age are due, in part, to how much excitement they ideally want to
      feel. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30299156
TI  - Anxiety and depression among adult amputees: the role of attachment insecurity,
      coping strategies and social support.
AB  - A number of studies have investigated the role of coping and social support as
      protective factors for psychosocial adjustment after amputation. In contrast, few
      have focused on the role of attachment styles. Therefore, the purpose of this
      study was to examine the relationship between attachment insecurity, social
      support, coping strategies and negative emotions, such as anxiety and depression,
      in adult amputees. Sixty-two amputated adults (71% males, 29% females), recruited
      from the Prosthetic Centre of the Italian Workers' Compensation Authority,
      completed the Attachment Style Questionnaire, the Coping Inventory for Stressful
      Situations, the Multidimensional Scale of Perceived Social Support, the Beck
      Depression Inventory II and the State-Trait Anxiety Inventory Y. Based on
      Pearson's correlations results, we conducted a mediation analysis to examine
      whether the association between attachment insecurity (i.e., attachment anxiety
      and attachment avoidance) and negative emotion (i.e. depression, state anxiety
      and trait anxiety) variables was mediated by emotion-oriented coping. Analyses
      revealed the role of insecure attachment styles in influencing the use of an
      emotion-oriented coping strategy in particular. The latter mediated the
      relationship between attachment insecurity, depression and anxiety in adult
      amputees.

PMID- 30299155
TI  - The mapping between transformed reaction time costs and models of processing in
      aging and cognition.
AB  - Older adults tend to have slower response times (RTs) than younger adults on
      cognitive tasks. This makes the examination of domain-specific deficits in aging
      difficult, as differences between conditions in raw RTs (RT costs) typically
      increase with slower average RTs. Here, we examine the mapping between 2
      established approaches to dealing with this confound in the literature. The first
      is to use transformed RT costs, with the z-score and proportional transforms both
      being commonly used. The second is to use mathematical models of choice RT
      behavior, such as the drift-diffusion model (Ratcliff, 1978). We simulated data
      for younger and older adults from the drift-diffusion model under 4 scenarios:
      (a) a domain specific deficit, (b) general slowing, (c) strategic slowing, and
      (d) a slowing of nondecision processes. In each scenario we varied the size of
      the difference between younger and older adults in the model parameters, and
      examined corresponding effect sizes and Type I error rates in the raw and
      transformed RT costs. The z-score transformation provided better control of Type
      I error rates than the raw or proportional costs, though did not fully control
      for differences in the general slowing and strategic slowing scenarios. We
      recommend that RT analyses are ideally supplemented by analyses of error rates
      where possible, as these may help to identify the presence of confounds. To
      facilitate this, it would be beneficial to include conditions that elicit below
      ceiling accuracy in tasks. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30299157
TI  - Distribution of tumor-infiltrating immune cells in glioblastoma.
AB  - AIM: Evaluation of features related to infiltrating immune cell level in
      glioblastoma. METHODS: Tumor-infiltrating lymphocytes (TILs) through H&E
      staining, and TILs (CD3, CD4, CD8 and CD20) and macrophage (CD68 and CD163)
      levels through immunohistochemistry were evaluated through digital analysis.
      RESULTS: CD68 (9.1%), CD163 (2.2%), CD3 (1.6%) and CD8 (1.6%) had the highest
      density. Higher CD4+ was associated with unmethylated MGMT (p = 0.016). Higher
      CD8+ was associated with larger tumoral size (p = 0.027). Higher CD163+ was
      associated with higher age (p = 0.044) and recursive partitioning analysis = 4.
      Women (p < 0.05), total resection (p < 0.05), MGMT-methylation (p < 0.001),
      radiotherapy (p < 0.001), chemotherapy (p < 0.001) and lower CD4+ (p < 0.05) were
      associated with longer overall survival. CONCLUSION: Macrophages are more
      frequent than TILs. Some subsets are associated with clinical features.

PMID- 30299158
TI  - High School Athletic Trainer Services for Knee Injuries.
AB  - CONTEXT: Participation in high school athletics carries a substantial risk of
      musculoskeletal injury, particularly to the knee. However, limited information is
      available on the care being provided by athletic trainers (ATs) for athletes with
      these injuries. DESIGN: Descriptive epidemiology study. SETTING: Data on athletic
      training facility visits and AT services were collected from 147 high schools in
      26 states. PATIENTS OR OTHER PARTICIPANTS: High school student-athletes who
      participated in 13 boys' sports and 14 girls' sports and sustained a diagnosed
      knee injury during the 2011-2012 through 2013-2014 academic years. The ATs
      documented 6797 knee injuries, with 4242 sustained in boys' sports and 2555
      sustained in girls' sports. MAIN OUTCOME MEASURE(S): The number of athletic
      training facility visits and individual AT services as well as the average,
      median, and interquartile range of athletic training facility visits (per injury)
      and AT services (per injury) were calculated by sport and for time-loss (TL;
      participation restricted for >=24 hours) and non-time-loss (NTL; participation
      restricted for <24 hours) injuries. RESULTS: In total, 28 788 athletic training
      facility visits were reported, with an overall average of 4 athletic training
      facility visits per knee injury over the 3-year period. Most athletic training
      facility visits (72.6%) were associated with NTL injuries, but the majority of AT
      services (68.6%) were associated with TL injuries. A total of 81 245 AT services
      were provided for all knee injuries. Therapeutic activities or exercise were the
      most common type of AT service (52.5%). Overall, an average of 12 AT services
      were reported per knee injury. Compared with NTL injuries, TL injuries had a
      larger average number of AT services per injury (34 versus 9; P < .001).
      CONCLUSIONS: Knee injuries at the high school level are a considerable health
      care burden. This report demonstrates a high proportion of AT attention to the
      evaluation and treatment of these injuries. This study confirms the recommended
      management of knee injuries, with neuromuscular and therapeutic activities being
      the primary services after knee injury.

PMID- 30299160
TI  - Vinorelbine cationic liposomes modified with wheat germ agglutinin for inhibiting
      tumor metastasis in treatment of brain glioma.
AB  - Glioma is the most common primary malignant brain tumor with a poor prognosis.
      The application of chemotherapeutic drugs is limited due to the existence of
      blood-brain barrier and serious side effects. Liposomes have been proven to be a
      stable and useful drug delivery system for tumors. In this paper, WGA (wheat germ
      agglutinin) modified vinorelbine cationic liposomes had been successfully
      constructed for treating glioma. In the liposomes, WGA was modified on the
      liposomal surface for crossing the blood-brain barrier and increasing the
      targeting effects, 3-(N-(N', N'-dimethylaminoethane) carbamoyl) cholesterol (DC
      Chol) was used as cationic material and vinorelbine was encapsulated in the
      aqueous core of liposomes to inhibit tumor metastasis and kill tumor cells.
      Studies were performed on C6 cells in vitro and were verified in brain glioma
      bearing mice in vivo. Results in vitro demonstrated that the targeting liposomes
      could induce C6 cells apoptosis, promote drugs across the blood-brain barrier,
      inhibit the metastasis of tumor cells and increase targeting effects to tumor
      cells. Meanwhile, action mechanism studies showed that the targeting liposomes
      could down-regulate PI3K, MMP-2, MMP-9 and FAK to inhibit tumor metastasis.
      Results in vivo exhibited that the targeting liposomes displayed an obvious
      antitumor efficacy by accumulating selectively in tumor site and exhibited low
      toxicity to blood system and major organs. Hence, WGA modified vinorelbine
      cationic liposomes might provide a safe and efficient therapy strategy for
      glioma.

PMID- 30299161
TI  - Loss of functional connectivity is an early imaging marker in primary lateral
      sclerosis.
AB  - OBJECTIVE: The clinical diagnosis of primary lateral sclerosis can only be made
      after upper motor neuron symptoms have progressed for several years without
      developing lower motor neuron signs. The goal of the study was to identify
      neuroimaging changes that occur early in primary lateral sclerosis, prior to
      clinical diagnosis. METHODS: MRI scans were obtained on 13 patients with adult
      onset progressive spasticity for five years or less who were followed
      longitudinally to confirm a clinical diagnosis of primary lateral sclerosis.
      Resting state functional MRI, diffusion tensor imaging, and anatomical images
      were obtained. These "pre-PLS" patients were compared to 18 patients with
      longstanding, established primary lateral sclerosis and 28 controls. RESULTS: Pre
      PLS patients had a marked reduction in seed-based resting-state motor network
      connectivity compared to the controls and patients with longstanding disease.
      White matter regions with reduced fractional anisotropy were similar in the two
      patient groups compared to the controls. Patients with longstanding disease had
      cortical thinning of the precentral gyrus. A slight thinning of the right
      precentral gyrus was detected in initial pre-PLS patients' scans. Follow-up scans
      in eight pre-PLS patients 1-2 years later showed increasing motor connectivity,
      thinning of the precentral gyrus, and no change in diffusion measures of the
      corticospinal tract or callosal motor region. CONCLUSIONS: Loss of motor
      functional connectivity is an early imaging marker in primary lateral sclerosis.
      This differs from literature descriptions of amyotrophic lateral sclerosis,
      warranting further studies to test whether resting-state functional MRI can
      differentiate between amyotrophic lateral sclerosis and primary lateral sclerosis
      at early disease stages.

PMID- 30299159
TI  - A Bilateral Comparison of the Underlying Mechanics Contributing to the Seated
      Single-Arm Shot-Put Functional Performance Test.
AB  - CONTEXT: Functional performance tests (FPTs) are tools used to assess dynamic
      muscle strength and power. In contrast to the lower extremity, fewer FPTs are
      available for the upper extremity. The seated single-arm shot put test has the
      potential to fill the void in upper extremity FPTs; however, the underlying
      mechanics have not been examined and, therefore, the validity of bilateral
      comparisons is unknown. OBJECTIVE: To examine the effects of upper extremity
      dominance and medicine-ball mass on the underlying mechanics of the seated single
      arm shot put. DESIGN: Crossover study. SETTING: Biomechanics laboratory. PATIENTS
      OR OTHER PARTICIPANTS: Fifteen women (age = 23.6 +/- 2.1 years, height = 1.65 +/-
      .07 m, mass = 68.1 +/- 11.7 kg) and 15 men (age = 24.3 +/- 4.0 years, height =
      1.80 +/- 0.06 m, mass = 88.1 +/- 16.4 kg), all healthy and physically active.
      INTERVENTION(S): Seated single-arm shot-put trials using the dominant and
      nondominant limbs were completed using three 0.114-m-diameter medicine-ball loads
      (1 kg, 2 kg, 3 kg). MAIN OUTCOME MEASURE(S): Customized touch-sensitive gloves,
      synchronized with kinematic data of the hands, signaled ball release, so that
      release height, release angle, and peak anterior and vertical velocity could be
      quantified for each trial. In addition, the horizontal range from release to
      first floor impact was recorded. RESULTS: The dominant-limb horizontal ranges
      were 7% to 11% greater ( P < .001) than for the nondominant limb for each of the
      3 ball masses. No bilateral release-height or -angle differences were revealed (
      P >= .063). Release velocities were 7.6% greater for the dominant limb than the
      nondominant limb ( P = .001). CONCLUSIONS: Our results support the use of the
      seated single-arm shot put test as a way to compare bilateral upper extremity
      functional performance. The near-identical release heights and angles between the
      dominant and nondominant limbs support the interpretation of measured bilateral
      horizontal-range differences as reflecting underlying strength and power
      differences.

PMID- 30299162
TI  - The palmomental reflex predicts earlier corticobulbar involvement in ALS.
AB  - OBJECTIVE: The palmomental reflex (PMR) is a primitive reflex, which may appear
      when cortical inhibitory pathways are disrupted by disease. In this study, we
      examined whether the PMR is associated with corticobulbar involvement in people
      with ALS (PALS). METHODS: PMR was routinely tested for each patient attending the
      ALS clinic. Three hundred and eighteen consecutive PALS were included, of whom
      271 were PMR positive (PMR+). Clinical evaluation defined the presence of upper
      motor neuron (UMN) and lower motor neuron (LMN) signs in the bulbar, cervical and
      lumbosacral segments. RESULTS: The PMR + group had a higher rate of both UMN and
      LMN bulbar involvement (BI) as well as more UMN upper-limb involvement and UMN
      involvement of any type, the strongest association being between PMR + and UMN
      BI. In patients without BI at presentation, UMN BI developed roughly 15 months
      early in the PMR + group compared to the PMR- group. CONCLUSION: We found that
      the PMR is strongly associated with UMN signs within the bulbar region and to a
      lesser extent with upper-limb UMN involvement. We propose the PMR be considered a
      harbinger of corticobulbar involvement in PALS.

PMID- 30299163
TI  - Ancient philosophers on mental illness.
AB  - This article explores how the ancient philosophers from Plato to late antiquity
      understood mental illness. It outlines when, how and in what kind of contexts the
      phenomenon of mental illness was recognized in the ancient philosophical texts,
      how mental illness was understood in terms of the body-mind interaction, and how
      mental disorders of the medical kind were distinguished from non-medical psychic
      disturbances. It establishes that, while the philosophers mostly understood
      mental illness along the lines of ancient medical thinking, their ideas, for
      example on the nature and location of the soul, informed their theories of mental
      illness.

PMID- 30299164
TI  - Determination of some adsorption and kinetic parameters of alpha-amylase onto
      Cu+2-PHEMA beads embedded column.
AB  - In order to investigate the biocatalytic properties of alpha-amylase on a
      composite cryogel matrix with immobilized metal affinity chromatography, Cu+2
      attached poly(2-hydroxyethyl methacrylate) (Cu+2-PHEMA) beads, (2 um size) were
      synthesized, then composite cryogel column was prepared by composing beads and
      PHEMA cryogels. After the preparation of Cu+2-PHEMA beads embedded cryogel column
      (Cu+2-BEC), some experiments were tested. Accordingly, the highest adsorption
      capacity (676.8 mg/g particles) of cryogels was achieved at acetate buffer of pH
      5.0 with initial alpha-amylase concentration of 4 mg/mL. Immobilized enzyme has
      more stable pH range, between 6 and 7.5 than, the free one. Immobilization also
      increased the optimal activity from 25 to temperature range of 25-35  degrees C.
      Vmax and Km of alpha-amylase were detected as 1.149 U/mg protein, and 11.6 * 10-1
      mM, respectively. alpha-Amylase was utilized 35 times repeatedly without losing
      the productivity.

PMID- 30299165
TI  - Mental Health and the Maintenance of Kinship in South Africa.
AB  - At the turn of the millennium, people with mental disturbance often lived in
      circumstances of economic marginalization in South Africa. The historical
      material of one low-income urban area reveals the place of kin relations and
      reciprocity in enabling negotiation of a more fluid set of responses to mental
      illness. In this sociocultural context, "stigma" was not an inevitable reaction
      to mental illness, and a more complex set of social dynamics could mitigate
      marginalization. Research on how changing informal care practices relate to state
      based community care continues to be important to inform contemporary health
      reforms.

PMID- 30299166
TI  - Risk of preterm birth in primiparous women with exposure to antidepressant
      medication before pregnancy and/or during pregnancy - impact of body mass index.
AB  - INTRODUCTION: Preterm birth is a major cause of infant mortality. It is unknown
      whether body mass index (BMI) influences the risk of preterm birth in women, who
      prenatally use antidepressants. MATERIALS AND METHODS: The study cohort (N =
      6920) consists of all primiparous European born women without previously
      diagnosed diabetes from the city of Vantaa, Finland, who delivered a singleton
      child between 2009 and 2015. Data on births, pre-pregnancy BMI and purchases of
      antidepressants from 12 months before conception until delivery were obtained
      from Finnish National Registers. RESULTS: Of the primiparous women, 9.9% used
      antidepressants. The overall prevalence of preterm birth was 5.2%. In women with
      a pre-pregnancy BMI <18.5 kg/m2, the Odds Ratio (OR) for preterm birth among
      antidepressant users compared with those who were non-users was 1.91 (95%
      confidence intervals [CI] 0.40 to 9.15, adjusted for age, smoking, education, use
      of fertility treatments and number of previous pregnancies) while in women with a
      pre-pregnancy BMI >=30 kg/m2, the OR was 0.53 (95% CI 0.21-1.36), respectively.
      DISCUSSION: Primiparous women using antidepressants, who were underweight before
      conception should be closely monitored and provided tailored care in a maternity
      clinic to minimize the risk of preterm birth. Key messages In primiparous women,
      one in ten used antidepressant medications before pregnancy and/or during
      pregnancy. In primiparous women, the prevalence of preterm birth was 5%.
      Underweight primiparous women using antidepressants should be closely monitored
      and provided tailored care in a maternity clinic.

PMID- 30299167
TI  - Making it work: experience of living with a person who falls due to multiple
      sclerosis.
AB  - PURPOSE: The purpose of this study was to describe how everyday life is
      experienced by next of kin sharing residence with a person who falls due to
      multiple sclerosis (MS). METHODS: Twenty face-to-face interviews were analysed
      using a qualitative content analysis. RESULTS: The overall theme "Making it work"
      represents the next of kin's struggle to make life work. It comprises three
      themes: "Taking responsibility", "Making adjustments", and "Standing aside for
      someone else". The two first themes reflect what relatives do to make the
      situation work, and the last theme represents what they give up. CONCLUSION: Next
      of kin who share residence and everyday life with a person with MS are affected
      by that person's occasional falls. They often take on the responsibility of
      preventing such falls and adapt their lives practically and emotionally. However,
      adaptation is neither always enough or always possible. In these cases, relatives
      often deprioritize their own needs and free time to make everyday life in the
      home work. Implications for rehabilitation By highlighting that next of kin also
      are affected by the falls of their cohabiting person with multiple sclerosis
      enhances the importance of fall prevention activities that should include the
      next of kin. Next of kin to people who occasionally fall due to multiple
      sclerosis can be in need of both practical and emotional support from the health
      care system. Enhanced information from the health care system can empower and
      help them to take care of themselves while managing to live with, care for, and
      protect the person with multiple sclerosis from falls.

PMID- 30299168
TI  - The NYC Health Department's Reflections on First-Ever Public Health Deployments
      in Support of Puerto Rico and the US Virgin Islands After the 2017 Hurricane
      Season.
AB  - In late 2017 and early 2018, the New York City Department of Health and Mental
      Hygiene deployed multiple teams to Puerto Rico and the US Virgin Islands to
      support public health in those territories. This article is a description of how
      those teams were conceived, deployed, supported, and reintegrated into the
      agency. This was an unprecedented mission for our agency, and what follows is a
      reflection on what worked and what didn't work for us. It is our hope that other
      jurisdictions can use this information to organize and execute similar missions
      in the future, and that collectively we can continue to advance the field of
      public health preparedness and response.

PMID- 30299169
TI  - miR-155 deletion modulates lipopolysaccharide-induced sleep in female mice.
AB  - : Immune signaling is known to regulate sleep. miR-155 is a microRNA that
      regulates immune responses. We hypothesized that miR-155 would alter sleep
      regulation. Thus, we investigated the potential effects of miR-155 deletion on
      sleep-wake behavior in adult female homozygous miR-155 knockout (miR-155KO) mice
      and littermate controls (WT). Mice were implanted with biotelemetry units and
      EEG/EMG biopotentials were recorded continuously for three baseline days. miR
      155KO mice had decreased bouts of NREM and REM sleep compared with WT mice, but
      no differences were observed in the length of sleep bouts or total time spent in
      sleep-wake states. Locomotor activity and subcutaneous temperature did not differ
      between WT and miR-155KO mice. Following baseline recordings, mice were sleep
      deprived during the first six hours of the rest phase (light phase; ZT 0-6)
      followed by an 18 h recovery period. There were no differences between groups in
      sleep rebound (% sleep and NREM delta power) after sleep deprivation. Following
      recovery from sleep deprivation, mice were challenged with a somnogen (viz.,
      lipopolysaccharide (LPS)) one hour prior to the initiation of the dark (active)
      phase. Biopotentials were continuously recorded for the following 24 h, and miR
      155KO mice displayed increased wakefulness and decreased NREM sleep during the
      dark phase following LPS injection. Additionally, miR-155KO mice had reduced EEG
      slow-wave responses (0.5-4 Hz) compared to WT mice. Together, our findings
      indicate that miR-155 deletion attenuates the somnogenic and EEG delta-enhancing
      effects of LPS. ABBREVIATIONS: ANOVA: analysis of variance; EEG:
      electroencephalogram; EMG: electromyogram; h: hour; IL-1: interleukin-1; IL-6:
      interleukin-6; IP: intra-peritoneal; LPS: lipopolysaccharide; miR/miRNA:
      microRNA; miR-155KO: miR-155 knockout; NREM: non-rapid eye movement; REM: rapid
      eye movement; TNF: tumor necrosis factor; SWS: slow-wave sleep; WT: wild-type.

PMID- 30299170
TI  - Discrimination between extreme chronotypes using the full and reduced version of
      the Morningness-Eveningness Questionnaire.
AB  - The aim of this study was to carry out a comparison of the ability to
      discriminate between extreme chronotypes, i.e., morning- and evening-types, among
      the Morningness-Eveningness Questionnaire (MEQ) and its reduced version (rMEQ).
      To this end a secondary analysis of cohort studies, using two different
      approaches, was carried out. The first, subjective, relied on the computing of
      overlap between extreme chronotypes according to their hourly ideal bedtime, get
      up time and midpoint of sleep reported at the MEQ and rMEQ, while the second,
      objective, on the corresponding actual-actigraphic times. At the subjective
      approach, 2706 participants filled in the MEQ, while 940 the rMEQ (age range of
      both groups: 18-30 years). The overlap was significantly lower among those who
      filled the rMEQ than MEQ when considering ideal midpoint of sleep (13.70% and
      46.28%, respectively) and get-up time (47.04% and 62.34%, respectively). At the
      objective approach, 51 participants filled in the MEQ while 52 the rMEQ (age
      range: 19-30 years in both groups) at the end of one week of actigraphic
      recording. No significantly different overlap across those who filled the MEQ or
      rMEQ was observed with reference to the examined actigraphic times. Results of
      subjective assessment showed as rMEQ more clearly discriminated between extreme
      chronotypes than MEQ. The attempt to find an objective confirmation did not
      provide the same results, probably as a consequence of a masking effect by social
      rhythms.

PMID- 30299171
TI  - A risk prediction model for renal damage in a hypertensive Chinese Han
      population.
AB  - : Backgroud: While numerous risk factors for renal damage in the hypertensive
      population have been reported, there is no single prediction model. The purpose
      of this study was to develop a model to comprehensively evaluate renal damage
      risk among hypertensive patients. Methods: We analyzed the data of 582 Chinese
      hypertensive patients from 1 January 2013 to 30 June 2016. Basic patient
      information was collected along with laboratory test results. According to the
      albumin-to-creatinine ratio, the subjects were divided into a hypertension with
      renal damage group and a hypertension without renal damage group. The prediction
      model was established by logistic regression based on principal component
      analysis, and the area under the receiver operating characteristic curve was used
      to evaluate the predictive performance of the model. RESULTS:  There are 11
      indicators have statistically significant difference between the two groups (P <
      0.05); The equation expressed including all 11 risk factors was as follows: Y = (
      0.236) - 0.1705 (sex) - 0.0098 (age) - 0.1067 (smoking history) + 0.0303
      (drinking history) - 0.3031 (CHD) + 0.1276 (diabetes history) - 0.0596 (CRP
      level) - 0.0732 (CysC level) + 0.0949 (beta2-MG level) + 0.5407 (blood pressure
      type) + 0.6470 (RRI). The calculated AUC was 74.4%; The risk in males was much
      higher than that in females of the same age. However, with increasing age, the
      male:female risk ratio gradually decreased. Conclusion: Eleven  indicators
      (including sex, age, smoking history, drinking history, coronary heart disease,
      diabetes history, C-reactive protein, CystatinC,  beta2-microglobulin protein,
      blood pressure type, renal artery resistance index)  may be the risk factors of
      renal damage in hypertension. Our regression equation provides a feasible means
      of predicting renal damage in Chinese hypertensive populations, and the model
      showed good predictive power. In addition, estrogen may confer a protective
      effect on the kidney. ABBREVIATIONS: PCA: principal component analysis; SLPs:
      synthetic latent predictors; CKD: chronic kidney disease; RRI: renal artery
      resistance index; MLR: multivariate logistic regression; CHD: coronary heart
      disease; UACR: urine trace albumin/uric creatinine ratio; CysC: CystatinC; TG:
      Triglyceride; CHO: cholesterol; HDL: high-density lipoprotein cholesterol; LDL:
      low-density lipoprotein cholesterol; CRP: C-reactive protein; HCY: homocysteine;
      UA: uric acid; AUC: area under the ROC curve; CVE: cardiovascular events; RFF:
      renal function related factor; PHF: personal history related factor; CVF:
      cardiovascular factor; GMF: glucose metabolism factor; IF: inflammatory factor;
      BPF: blood pressure factor.

PMID- 30299172
TI  - "Human Life is Inviolable": Costa Rica's Human Rights Crucible.
AB  - The Costa Rican Constitutional Court banned in vitro fertilization in 2000,
      citing the inviolability of life. Conservatives hoped the ban would initiate a
      hemispheric movement to protect the unborn. But in 2012 the Inter-American Court
      of Human Rights ruled that reproductive rights are human rights and that women's
      rights take precedence over embryo rights. The episode precipitated a national
      identity crisis: how could a country that supports universal health care be
      labeled a human rights violator as a result of its efforts to protect nascent
      human life? Expanding the health and human rights framework helps us appreciate
      how IVF became Costa Rica's human rights crucible.

PMID- 30299173
TI  - The quality of care questionnaire: development of a valid measure for persons
      with inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Quality of care is important in lifelong illnesses such as
      inflammatory bowel disease (IBD). Valid, reliable and short questionnaires to
      measure quality of care among persons with IBD are needed. The aim of this study
      was to develop a patient-derived questionnaire measuring quality of care in
      persons with IBD. METHODS AND RESULTS: The development of the questionnaire The
      Quality of Care -Questionnaire (QoC-Q) was based on a literature review of
      studies measuring quality of care, and the results of two qualitative studies
      aiming to identify the knowledge need and perception of health care among persons
      with IBD. Further development and evaluation was done by focus groups, individual
      testing and cognitive interviews with persons with IBD, as well as evaluation by
      a group of professionals. After the development, the questionnaire was tested for
      validity and test-retest reliability in 294 persons with IBD. CONCLUSIONS: The
      QoC-Q is showing promising validity and reliability for measuring the subjective
      perception of quality of care. Further testing in clinical practice is suggested
      to assess if the QoC-Q can be used to evaluate care and areas of improvement in
      health care for persons living with IBD.

PMID- 30299174
TI  - Core-shell microencapsulation of curcumin in PLGA microparticles: programmed for
      application in ovarian cancer therapy.
AB  - In our study, we have established a novel liquid-driven co-flow focusing (LDCF)
      process to fabricate curcumin (CUR)-loaded poly (lactic-co-glycolic acid) (PLGA)
      microparticles (CPMs). LDCF-CPMs of size 20.26 +/- 2.37 MUm have high
      encapsulation efficiency (>70%) and were intended for application in ovarian
      cancer by intraperitoneal (IP) administration. LDCF-CPMs have smooth surface with
      narrow size distribution and a core-shell structured verified by confocal
      microscopy which can be precisely controlled by changing the flow rates of
      focusing, outer and inner phases. The LDCF-CPMs reveal the physiochemical
      stability with sustained release profile corresponding to 95% CUR release over a
      period of 14 days in an in vitro release medium. Moreover, LDCF-CPMs were
      testified for cytotoxicity against SKOV-3 ovarian cancer cell lines and
      peritoneal delivery advantages by animal experiments. The pharmacokinetics of
      LDCF-CPMs in rats following IP injection shows slow systemic absorption with mean
      residence time (MRT) of 13.54 h in comparison with 9.82 and 6.74 h for SE-CPMs
      and free CUR, respectively. In addition, IP delivery of CUR can expose the
      ovarian tumour to higher concentration for a longer duration by programming the
      thickness of the shell. The study provides compelling evidence for LDCF-CPMs
      having high therapeutic opportunity in the treatment of peritoneal cancers, such
      as ovarian, that reside in the peritoneal cavity.

PMID- 30299175
TI  - Analysis of the risk factors for contrast-induced nephropathy in over-aged
      patients receiving coronary intervention.
AB  - Contrast-induced nephropathy has been the common cause of hospital-acquired acute
      kidney injury in the elderly patients. This study aimed to analyze the risk
      factors for contrast-induced nephropathy in over-aged patients undergoing
      coronary angiography or percutaneous coronary intervention. A total of 470 over
      aged patients (>=80 years old) were judged as the contrast-induced nephropathy
      group ( n = 46) and non-contrast-induced nephropathy group ( n = 424) according
      to the postoperative 48-h serum creatinine levels. The patients' clinical
      information such as hypertension grade, number and degree of coronary artery
      stenosis, and death rate was compared. The risk factors for contrast-induced
      nephropathy were also analyzed. The hypertension grade in the contrast-induced
      nephropathy group was significantly higher than that in the non-contrast-induced
      nephropathy group ( P = 0.004). The degree of coronary artery stenosis was
      significantly more in the contrast-induced nephropathy group compared with the
      non-contrast-induced nephropathy group ( P = 0.003). The death rate of the
      contrast-induced nephropathy group (15.8%) was significantly higher than that of
      the non-contrast-induced nephropathy group (0.6%; P = 0.000). The percentage of
      patients with abnormal urine microalbumin was significantly bigger in the
      contrast-induced nephropathy group (62.5%) when comparing to the non-contrast
      induced nephropathy group (23.6%; P = 0.00). Besides, there was also significant
      difference in the emergency/selective operation between the contrast-induced
      nephropathy group and non-contrast-induced nephropathy group ( P = 0.001).
      Further, hypertension grade ( P = 0.019), emergency/selective operation ( P =
      0.025), degree of coronary artery stenosis ( P = 0.038), eGFR ( P = 0.034), and
      urine microalbumin ( P = 0.005) were the risk factors for contrast-induced
      nephropathy. Hypertension grade, emergency/selective operation, degree of
      coronary artery stenosis, eGFR, and urine microalbumin were the risk factors for
      contrast-induced nephropathy in over-aged patients receiving coronary angiography
      and percutaneous coronary intervention, providing guidance for the clinical
      prevention of contrast-induced nephropathy. Impact statement In this work, we
      evaluated the risk factors for contrast-induced nephropathy (CIN) in over-aged
      patients receiving coronary angiography (CAG) and percutaneous coronary
      intervention (PCI). We found that hypertension grade, emergency/selective
      operation, degree of coronary artery stenosis, eGFR, and urine microalbumin were
      the risk factors for CIN in over-aged patients receiving CAG and PCI. This study
      provides guidance for the clinical prevention of CIN in over-aged patients
      undergoing coronary intervention, highlighting that a perioperative comprehensive
      management strategy is needed to improve the prognosis.

PMID- 30299176
TI  - An exploration of the experiences and utility of functional electrical
      stimulation for foot drop in people with multiple sclerosis.
AB  - PURPOSE: Functional electrical stimulation (FES) is effective in improving
      walking in people with multiple sclerosis (MS) with foot drop. There is limited
      research exploring people's experiences of using this device. This study aims to
      explore the utility, efficacy, acceptability, and impact on daily life of the
      device in people with MS. METHODS: An interpretative phenomenological approach
      was employed. Ten participants who had used FES for 12 months were interviewed.
      Transcripts were analysed, and emergent themes identified. RESULTS: Nine
      participants continued to use the device. Three relevant super-ordinate themes
      were identified; impact of functional electrical stimulation, sticking with
      functional electrical stimulation, and autonomy and control. Participants
      reported challenges using the device; however, all reported positive physical and
      psychological benefits. Intrinsic and external influences such as; access to
      professional help, the influence of others, an individual's ability to adapt, and
      experiences using the device, influenced their decisions to continue with the
      device. A thematic model of these factors was developed. CONCLUSIONS: This study
      has contributed to our understanding of people with MS experiences of using the
      device and will help inform prescribing decisions and support the continued,
      appropriate use of FES over the longer term. Implications for Rehabilitation
      People with multiple sclerosis using functional electrical stimulation report
      benefits in many aspects of walking, improved psychological well-being and
      increased engagement in valued activities. A number of challenges impact on
      functional electrical stimulation use. Factors such as; a positive experience
      using the device, access to professional help, the influence of others, a strong
      sense of personal autonomy and an individual's ability to adapt, influence an
      individual's decision to continue using functional electrical stimulation.
      Clinicians prescribing functional electrical stimulation should be aware of these
      factors so that the right support and guidance can be provided to people with
      multiple sclerosis, thus improving outcomes and compliance over the long term.

PMID- 30299177
TI  - Commentary.

PMID- 30299178
TI  - A Randomized Double-Blind Trial of Ginger Root for Reducing Muscle Soreness and
      Improving Physical Performance Recovery Among Experienced Recreational Distance
      Runners.
AB  - Previous studies indicate that ginger root has pain-relieving properties, but
      these effects have not been thoroughly examined in the context of distance
      running. The purpose of this randomized, double-blind, placebo-controlled trial
      was to determine whether ginger root supplementation reduces muscle soreness and
      dysfunction from downhill running. Thirty-two runners (10 women, 22 men) were
      pair-matched and randomized to 1.425 g/day of ginger root or placebo for 5 days.
      A 40-minute downhill (-7.5%) run was completed on day 3. Before supplementation
      and at various points throughout a 5-day protocol, muscle soreness, pain-pressure
      threshold, vertical jump, and 1.5-mile run performance were evaluated.
      Differences between treatments were assessed using magnitude-based inferential
      statistics. Soreness while jogging likely increased to a lesser degree with
      ginger root from baseline to immediately postrun (Cohen's d = -0.69; 90%
      confidence limit [CL] [-1.50, 0.12]) and from baseline to day 5 (d = -0.72; 90%
      CL [-1.61, 0.16]). Ginger root had a possible small benefit on vertical jump from
      baseline to day 5 (d = 0.24; 90% CL [0.05, 0.44]) but likely no meaningful impact
      on 1.5-mile run performance. Trivial or unclear effects were found for most other
      outcomes. No significant differences in adverse events were observed between
      treatments. Ginger root possibly has moderate beneficial effects on running
      induced soreness but likely irrelevant effects on recovery of physical
      performance. Ginger represents one option for runners looking to temporarily
      reduce pain, although more studies are warranted to clarify its safety profile
      and its effects on long-term training adaptation.

PMID- 30299180
TI  - Cardioprotective Efficacy of Coriandrum sativum (L.) Seed Extract in Heart
      Failure Rats Through Modulation of Endothelin Receptors and Antioxidant
      Potential.
AB  - The present study aimed to evaluate the therapeutic and prophylactic potential of
      Coriandrum sativum extract in isoproterenol-induced heart failure (HF) in Wistar
      rats. Two weeks after the isoproterenol administration, rats developed severe
      impairment in left ventricular functions, reduced baroreflex sensitivity, and
      significant alteration in hemodynamic parameters and lipid profile. HF rats also
      exhibited enhanced lipid peroxidation and increased expression of endothelin
      receptors (ETA and ETB). Therapeutic and prophylactic treatment with C. sativum
      extract significantly (p < .05) improved the left ventricular functions and
      hemodynamic parameters and increased baroreflex sensitivity. It also inhibited
      lipid peroxidation, improved lipid profile, and downregulated the expression of
      endothelin receptors. Simvastatin treatment showed a similar cardioprotective
      effect. Our results suggest that C. sativum extract provides significant
      protection from heart failure possibly due to its ability to improve left
      ventricular functions and baroreflex sensitivity, attenuate lipid peroxidation,
      and modulate the expression of endothelin receptors.

PMID- 30299179
TI  - Role of microRNA-223 in the regulation of poly(ADP-ribose) polymerase in
      pediatric patients with Crohn's disease.
AB  - OBJECTIVES: Crohn's disease (CD) is a multifactorial disease, characterized by
      oxidant-induced tissue injury with a possible activation of poly(ADP-ribose)
      polymerase (PARP)-1. MicroRNAs (miRs) can offer a potential link between the
      genetic susceptibility, environmental and immunologic factors in the pathogenesis
      of CD. Previously, PARP-1 was identified as a direct target gene of miR-223 in an
      epithelial cell line. Our aim was to examine PARP activation and miR-223
      expression in colonic biopsies of pediatric CD. To support our in vivo findings,
      the effect of lipopolysaccharide (LPS) on same parameters was examined in HT-29
      colonic epithelial cell line. METHODS: Colonic biopsies were taken from patients
      with macroscopically inflamed and intact mucosa with CD and controls. LPS treated
      HT-29 cells served as our in vitro model. To analyze the PARP-1 expression real
      time PCR, Western blot and immunohistochemical analyses were used. PARP-1
      enzymatic activity was assessed on the basis of poly(ADP-ribosyl)ated proteins.
      Expression of miR-223 was examined by real-time PCR. RESULTS: PARP-1 mRNA and miR
      223 expression was significantly elevated, however, the amount of PARP-1 protein
      and poly(ADP-ribose) was reduced in pediatric CD compared to controls. LPS
      incubation did not affect the expression of PARP-1 mRNA, however, decreased miR
      223 expression, and enhanced PARP-1 activity. CONCLUSIONS: In our study, we
      showed that the expression of miR-223 is up-regulated and poly(ADP-ribosyl)ation
      is reduced in pediatric patients with CD. Moreover, we confirmed their opposite
      change in LPS treated epithelial cells, too. These data suggest that the
      hypofunctionality of PARP-1 may play a potential role in the pathomechanism of
      CD.

PMID- 30299181
TI  - Ozone pollution and asthma emergency department visits in the Central Valley,
      California, USA, during June to September of 2015: a time-stratified case
      crossover analysis.
AB  - OBJECTIVE: The San Joaquin Valley (SJV) exceeds the state and national standards
      for ozone (O3). This study investigates whether short-term exposure to O3 is
      associated with asthma emergency department (ED) visits. METHODS: We identified
      1,101 ED visits in June-September of 2015 in SJV, California, who lived within 15
      km of active air monitors. Conditional logistic regression models were used to
      obtain the odds ratio (OR) and 95% confidence interval (CI) associated with an
      interquartile (IQR) increase in ozone. We explored the potential effect
      modification by sex (female and male), race (White, Black and Hispanic), age (2
      5, 6-18, 19-40, 41-64 and > = 65) and county (Merced, Madera, Kings, Fresno and
      Kern). RESULTS: An IQR range (18.1 ppb) increase in O3 exposure three days before
      an asthma attack (lag 3) was associated with a 6.6% [OR: 1.066 (95% CI: 1.032,
      1.082)] increase in the odds of having an asthma ED visit. The overall ORs
      differed across age groups and races/ethnicities, with strongest for children
      aged 6-18 years [OR: 1.219 (95% CI: 1.159, 1.280)], adults 19-40 years [OR: 1.102
      (95% CI: 1.053, 1.154)] and Blacks [OR: 1.159 (95% CI: 1.088, 1.236)],
      respectively. O3 exposure was not positively associated with asthma ED visits for
      Whites, while it was for other underrepresented groups. Fresno had the highest
      number of asthma ED visits and positive association among all five counties.
      CONCLUSION: We found that O3 exposure is associated with asthma ED visits in the
      SJV.

PMID- 30299182
TI  - Patients' attitudes toward treatment withdrawal in inflammatory bowel disease.

PMID- 30299183
TI  - Indigenous Health Curriculum and Health Professional Learners: A Systematic
      Review.
AB  - BACKGROUND: Globally, an estimated 370 million Indigenous peoples reside in more
      than 70 countries with these people commonly experiencing health care access
      inequity. PURPOSE: This systematic review aimed to examine the impact of
      Indigenous health care curriculum on entry-level health professional learners in
      preparation to deliver equitable health care. METHODS: Seventeen articles were
      identified and analyzed for: context; study design; study measures, teaching and
      learning delivery mode, content and duration; positive and negative learner
      reactions; learning gained and article quality was assessed using the Medical
      Education Research Study Quality Instrument. RESULTS: Most included studies
      described face-to-face delivery along with blended learning combining a placement
      in an Indigenous setting, stand-alone placements and digital learning.
      Descriptions of learning gained covered five domains: remembering, understanding,
      self-knowledge, perspective and application relating mostly to cultural
      awareness. Factors contributing to positive learner reactions included attitude,
      environment, educator skill, pedagogy and opportunities. Factors contributing to
      negative learner reactions included attitude and environment. CONCLUSIONS: There
      is a need to further explore how health professional graduates are prepared to
      work in Indigenous health and the appropriate measures to do this. There is
      opportunity to learn more about Indigenous health teaching and learning across
      learning domains, in mainstream clinical placements and in digital learning.

PMID- 30299184
TI  - Contemporary Nutrition Interventions to Optimize Performance in Middle-Distance
      Runners.
AB  - Middle-distance runners utilize the full continuum of energy systems throughout
      training, and given the infinite competition tactical scenarios, this event group
      is highly complex from a performance intervention point of view. However, this
      complexity results in numerous potential periodized nutrition interventions to
      optimize middle-distance training adaptation and competition performance. Middle
      distance race intensity is extreme, with 800m to 5,000m races being at ~95 to
      130% of VO2max. Accordingly, elite middle-distance runners have primarily Type
      IIa / IIx fiber morphology and rely almost exclusively on carbohydrate (primarily
      muscle glycogen) metabolic pathways for producing ATP. Consequently, the
      principle nutritional interventions that should be emphasized are those that
      optimize muscle glycogen contents to support high glycolytic flux (resulting in
      very high lactate values, of >20mmol/L in some athletes) with appropriate
      buffering capabilities, while optimizing power to weight ratios, all in a macro
      and micro-periodized manner. From youth to elite level, middle-distance athletes
      have arduous racing schedules (10-25 races/year), coupled with excessive global
      travel, which can take a physical and emotional toll. Accordingly, proactive and
      integrated nutrition planning can have a profound recovery effect over a long
      race season, as well as optimizing recovery during rounds of championship racing.
      Finally, with evidence-based implementation, and an appropriate risk/reward
      assessment, several ergogenic aids may have an adaptive and/or performance
      enhancing effect in the middle-distance athlete. Given that elite middle-distance
      athletes undertake ~400 to 800 training sessions with 10 to 25 races/year, there
      are countless opportunities to implement various periodized acute and chronic
      nutrition-based interventions to optimize performance.

PMID- 30299185
TI  - Medical College of the Future: from Informative to Transformative.
AB  - The complexity of medical education and healthcare systems is a 'wicked problem'.
      Change will be a continuous iteration between evaluation and revaluation.
      Medicine is a social science. It is about people, societies and human interaction
      and communication. Medical College of the future should be developed in the light
      of social constructivism theories. Students from year one, day one, should be
      embedded in the work environment. Academic Healthcare Systems will be the norm
      not the exceptional. The training of students will be in all healthcare related
      facilities in the community. Public-private partnership in education and research
      will spread and become more regulated and encouraged. The students who want to be
      the future physicians should be selected differently. The curriculum will be more
      context related. Entrustable professional activities will be measured more
      frequently at different points of the students learning trajectory. Research and
      innovation will be integral to the students' learning experience. They should be
      exposed to how researchers think and behave and be embedded in a research
      environment. The medical college of the future will be using advanced technology
      which will be disruptive and transform existing educational models. E-Learning
      materials will be shared by consortia of collaborating medical colleges from all
      around the world. Artificial intelligence and machine learning will influence how
      students learn. National and international accreditation systems should ensure
      quality, but not stifle innovation. Physical learning spaces should reflect and
      express the underlying assumptions about "what is learning and teaching?". This
      should be reflected and expressed through the design of its buildings,
      infrastructure, technology, furniture and out of class learning environment.
      Predicting the future is difficult in a rapidly changing world. Next generation
      physicians should be competent in treating the next generation of patients while
      maintaining the health of the population.

PMID- 30299186
TI  - Total Energy Expenditure, Physical Activity Level, and Water Turnover of
      Collegiate Dinghy Sailors in a Training Camp.
AB  - Prior studies have examined offshore sailing and energy strategies using accurate
      total energy expenditure (TEE) measurement in free-living conditions. However, no
      research has studied energy and water requirement during dinghy class sailing
      such as an Olympic event with concentrated training. This study aimed to
      investigate the TEE, physical activity level (PAL), and water turnover (rH2O) of
      collegiate dinghy sailors in a training camp using the doubly labeled water (DLW)
      method. Eleven dinghy sailing collegiate athletes (9 males and 2 females)
      participated. The DLW method was used to determine the participants' TEE and PAL
      over 8 days (6 training, 2 non-training days). Participants trained approximately
      7 h/day on water. Body fat was measured using a stable-isotope dilution method.
      The rH2O was estimated using deuterium turnover. The mean TEE, PAL, and rH2O were
      17.30 +/- 4.22 MJ/day (4133 +/- 1009 kcal/day), 2.8 +/- 0.3 (range, 2.1 to 4.1),
      and 3.3+/-0.7 (range, 2.6 to 4.5) L/day, respectively. To our knowledge, this was
      the first study to use the DLW method to determine TEE, PAL, and rH2O as
      references for competitive dinghy sailors in a spring training camp. Our results
      may serve as a reference to assist competitive dinghy sailors in determining
      their required nutritional support.

PMID- 30299187
TI  - 2018 Consensus framework for good assessment.
AB  - INTRODUCTION: In 2010, the Ottawa Conference produced a set of consensus criteria
      for good assessment. These were well received and since then the working group
      monitored their use. As part of the 2010 report, it was recommended that
      consideration be given in the future to preparing similar criteria for systems of
      assessment. Recent developments in the field suggest that it would be timely to
      undertake that task and so the working group was reconvened, with changes in
      membership to reflect broad global representation. METHODS: Consideration was
      given to whether the initially proposed criteria continued to be appropriate for
      single assessments and the group believed that they were. Consequently, we
      reiterate the criteria that apply to individual assessments and duplicate
      relevant portions of the 2010 report. RESULTS AND DISCUSSION: This paper also
      presents a new set of criteria that apply to systems of assessment and,
      recognizing the challenges of implementation, offers several issues for further
      consideration. Among these issues are the increasing diversity of candidates and
      programs, the importance of legal defensibility in high stakes assessments,
      globalization and the interest in portable recognition of medical training, and
      the interest among employers and patients in how medical education is delivered
      and how progression decisions are made.

PMID- 30299188
TI  - Spectacle Compliance and Its Determinants in a School Vision Screening Pilot in
      Botswana.
AB  - PURPOSE: The effectiveness of school eye health programmes relies on many
      factors, including compliance with spectacle wear. The objectives of this study
      were to determine spectacle compliance in a school vision screening pilot
      programme in Botswana, and investigate factors predictive of compliance. METHODS:
      The study was an observational, cross-sectional follow-up of a pilot school
      screening programme. Unannounced compliance checks were completed after 3-4
      months in a convenience sample of 19 schools. Sex, age, school level, visual
      acuity, and refractive error were analysed using logistic regression to
      investigate factors predictive of compliance. FINDINGS: Compliance data were
      recorded for 193/286 (67.5%) children; 62.2% were female and the median age was
      15 years (interquartile range 12-17 years). 60.1% of the sample were compliant
      with spectacle wear. Girls were more likely to be compliant than boys (adjusted
      odds ratio (aOR) = 2.32, 95% confidence interval (CI) 1.03-5.27). Children at
      primary and junior secondary school were more likely to be complaint than senior
      secondary school children (aOR = 16.96, 95% CI 5.60-51.39; and aOR = 3.39, 95% CI
      1.39-8.22, respectively). Children with binocular uncorrected visual acuity
      (UCVA) of 6/7.5 to 6/12 were 2.76 (95% CI1.05-7.23) times more likely to be
      compliant than children with binocular UCVA of 6/6. CONCLUSION: Compliance was
      higher in Botswana than previous African studies; however, improvement in this
      area would increase the effectiveness of the programme. Further investigation
      into barriers to spectacle wear affecting boys and older children is warranted. A
      prescribing protocol to avoid low prescriptions - especially where binocular UCVA
      is 6/6 - is desirable.

PMID- 30299189
TI  - Preclinical Pharmacokinetics of a Novel anti-c-Met Antibody-Drug Conjugate, SHR
      A1403, in Rodents and Non-human Primates.
AB  - 1. The in vivo pharmacokinetics (PK) profiles of a novel c-Met antibody-drug
      conjugate (ADC), SHR-A1403, were investigated and characterized in mice, rats and
      monkeys. 2. Serum concentrations of ADC and total antibody were detected using
      validated ELISA methods. The results showed low systemic clearance of both ADC
      and total antibody in all three species as reflected by gradual decrease in serum
      concentrations. Half-life (t1/2) of ADC ranged from 4.6 to 11.3 days in the three
      species. 3. Tissue distribution study in tumor-bearing mice showed high
      accumulation of 125I-SHR-A1403 in tumor tissues over the other organs/tissues,
      indicating the favourable safety of SHR-A1403 and characteristics of an ADC drug.
      4. Relatively low grade of anti-drug antibody (ADA) in monkeys had no impact on
      PK profile of the ADC. 5. During discovery stage, undesirable exposure and/or ADA
      incidence were observed for SHR-A1403 with high or low drug-antibody ratio (DAR),
      which was DAR = 5 to 6 and DAR = 1, respectively, and therefore prompted
      selection of an appropriate DAR value (DAR = 2) for SHR-A1403 used in preclinical
      development and clinical trials. 6. In conclusion, our work demonstrated
      favourable PK characterization of SHR-A1403, and supported for investigational
      new drug application (IND) and the ongoing first-in-human trial in the US.

PMID- 30299190
TI  - Observing neck movements evokes an excitatory response in the sympathetic nervous
      system associated with fear of movement in patients with chronic neck pain.
AB  - The objective of this study was to evaluate the response of the sympathetic
      excitatory nervous system in patients with chronic neck pain compared with a
      control group of asymptomatic subjects who underwent an intervention of watching
      activities involving movements in the neck region. Thirty participants were
      divided into two groups: patients with chronic neck pain (n = 15) and the control
      group (n = 15). The patients' neck disability, fear of movement and catastrophism
      were assessed with a self-report. The recorded variables related to the autonomic
      nervous system were skin conductance and skin temperature. The ANOVA test
      revealed significant differences in the increase in skin conductance in the
      chronic neck pain group after observing the activities (both in the photographs
      and video) at the end of the observation and 5 minutes after the intervention (p
      < .01; d > 0.80). There were no significant differences in skin temperature.
      Ultimately, the correlation analysis revealed a moderate positive correlation
      between kinesiophobia and skin conductance at 30 seconds (r = 0.53) and at 60
      seconds (r = 0.52) of observing the activities in the video for the chronic neck
      pain group. Based on the results of the present study, we suggest that observing
      activities involving neck movements causes an activation of the sympathetic
      excitatory nervous system in patients with chronic neck pain. These changes could
      be related to a fear of movement when faced with visual exposure to neck
      movements that could be interpreted as 'harmful' or 'dangerous'.

PMID- 30299191
TI  - The clarion call for a third wave in medical education to optimise healthcare in
      the twenty-first century.
AB  - During the years preceding 1910, the education and training of physicians
      (doctors) -to-be was based mainly on a master-apprentice model; the primary focus
      then was on the teaching and development of clinical skills. In 1910, however,
      Abraham Flexner submitted a highly influential report to the American medical
      authorities: in it, he recommended that all medical schools should be university
      based and that, importantly, medical practice should have a scientific basis
      strongly underpinned by the basic medical sciences. The recommendation provided
      the impetus for the design of medical education that begins with a pre-clinical
      phase to provide the strong scientific foundation for the clinical phase that
      follows. During the clinical phase, student learning will focus primarily on the
      clinical sciences relating to the diagnosis, treatment and management of patient
      care. Thus, two key 'pillars' (the basic sciences and the clinical sciences) of
      medical education were established; this two pillar model of medical education
      persisted for many decades thereafter and remained so till today. However, in
      order to optimise delivery of health care this must be viewed as an 'eco-system'
      taking into account the practice setting both present and future. The authors
      will attempt to provide a background to the changing trends in medical education
      and the changing practice environment, due primarily to the disruptive forces of
      change in this article.

PMID- 30299192
TI  - Sports Foods and Dietary Supplements for Optimal Function and Performance
      Enhancement in Track and Field Athletes.
AB  - Athletes are exposed to numerous nutritional products, attractively marketed with
      claims of optimizing health, function and performance. However, there is limited
      evidence to support many of these claims, and the efficacy and safety of many
      products is questionable. The variety of nutritional aids considered for use by
      track and field athletes includes sports foods, performance supplements and
      therapeutic nutritional aids. Support for sports foods, and five evidence-based
      performance supplements (caffeine, creatine, nitrate/beetroot juice, beta-alanine
      and bicarbonate) varies according to the event, the specific scenario of use and
      the individual athlete's goals and responsiveness. Specific challenges include
      developing protocols to manage repeated use of performance supplements in multi
      event or heat-final competitions or the interaction between several products
      which are used concurrently. Potential disadvantages of supplement use include
      expense, false expectancy and the risk of ingesting banned substances sometimes
      present as contaminants. However, a pragmatic approach to the decision-making
      process for supplement use is recommended. We conclude that it is pertinent for
      sports foods and nutritional supplements to be considered only where a strong
      evidence-base supports their use as safe, legal and effective; and that such
      supplements are trialed thoroughly by the individual before committing to use in
      a competition setting.

PMID- 30299193
TI  - Differences in foot contact times between obese and non-obese postmenopausal
      women when crossing obstacles.
AB  - OBJECTIVE: This study aimed to investigate the foot contact time differences
      between obese and non-obese subjects during walking when crossing obstacles.
      METHODS: Ninety-eight postmenopausal women were assigned to four groups, and
      their plantar pressure temporal data were collected using a two-step protocol
      during walking when crossing an obstacle set at 30% height of lower limb length
      of each subject. The initial, final, and duration of contact of 10 foot areas
      were measured. RESULTS: Leading limb: (1) the heel groups initiated foot contact
      using the heel, and the non-heel groups initiated contact using the metatarsals;
      (2) heel obese subjects showed an earlier initial contact and a longer contact
      duration of metatarsals 2-3; (3) non-heel obese subjects showed an earlier
      midfoot initial contact. Regarding the trailing limb: (4) heel obese subjects
      showed an earlier midfoot initial contact and a longer contact duration of
      metatarsal 5; (5) non-heel obese subjects showed an earlier initial contact and a
      longer contact duration of metatarsals 4-5. CONCLUSIONS: (1) The non-heel groups'
      foot rollover pattern may result from an attempt of rapidly restoring stability;
      (2) the heel obese subjects seem to regulate their plantar foot muscles to
      overcome their overweight; (3) the overweight of the non-heel obese subjects
      leads to a quicker backward foot roll-over from the metatarsals to the heel; (4)
      the overweight of the heel obese subjects can distort their footprints and/or
      their higher inertia may precipitate an anticipation of the midfoot contact,
      which can also explain the result observed for 5.

PMID- 30299194
TI  - MiR-216a inhibits proliferation and promotes apoptosis of human airway smooth
      muscle cells by targeting JAK2.
AB  - OBJECTIVE: Accumulating evidence suggests that aberrantly expressed microRNAs in
      airway smooth muscle (ASM) cells could change airway remodeling during the
      development of asthma. However, the underlying functions of microRNAs in ASM cell
      proliferation and apoptosis need to be further elucidated. METHODS: By using RT
      qPCR, miR-216a expression level was examined in the asthmatic patients and non
      asthmatic individuals. Cell proliferation assay and flow cytometry analysis were
      used in ASM cells in which miR-216a was an abnormal expression. MiR-216a
      predicted to target gene was explored by bioinformatic software, and further
      analyzed by Western blotting and luciferase reporter assay. RESULTS: Our results
      demonstrated that miR-216a levels were considerably lower in the ASM cells of
      asthmatic patients than in those of non-asthmatic individuals. Further study
      verified that the overexpression of miR-216a markedly suppressed cell
      proliferation and promoted cell apoptosis, whereas the knockdown of miR-216a had
      opposite effects in ASM cells. In addition, luciferase reporter assays and
      Western blotting identified that JAK2 was the direct functional target of miR
      216a, and the ectopic expression of JAK2 partially rescued the inhibitory effect
      of miR-216a in ASM cells. CONCLUSIONS: The above data indicate that miR-216a may
      function as a key regulator of airway remodeling by targeting JAK2, thus
      suggesting the potential role of miR-216a in the pathogenesis of asthma.

PMID- 30299195
TI  - What's in Your Beet Juice? Nitrate and Nitrite Content of Beet Juice Products
      Marketed to Athletes.
AB  - Consumption of beetroot juice (BRJ) supplements has become popular among
      athletes, because beets tend to be rich in nitrate (NO3-), which can enhance
      exercise performance by increasing nitric oxide production. The NO3- content of
      beets can vary significantly, however, making it difficult to know how much NO3-
      any product actually contains. Samples from 45 different lots of 24 different BRJ
      products from 21 different companies were therefore analyzed for NO3- (and
      nitrite; NO2-) concentration using high performance liquid chromatography. The
      NO3- and NO2- content, i.e., amount per serving, was then calculated based on
      either 1) the manufacturer's recommended serving size (for prepackaged/single
      dose products) or 2) as used in previous studies, a volume of 500 mL (for BRJ
      sold in bulk containers). There was moderate-to-large variability in NO3- content
      between samples of the same product, with a mean coefficient of variation of 30+/
      26% (range 2 to 83%). There was even greater variability between products, with a
      ~50-fold range in NO3- content between the lowest and highest. Only five products
      consistently provided >=5 mmol of NO3- per serving, which seems to be the minimal
      dose required to enhance exercise performance in most individuals. NO2- contents
      were generally low (i.e., <=0.5% compared to NO3-), although two products
      contained 10 and 14%. The present results may be useful to athletes and their
      support staff contemplating which (if any) BRJ product to utilize. These data may
      also offer insight into variability in the literature with respect to the effects
      of BRJ on exercise performance.

PMID- 30299196
TI  - Plus CA Change, plus C'Est Pareil: Making a Continued Case for the Use of MCQs in
      Medical Education.
AB  - Despite the increased emphasis on the use of workplace-based assessment in
      competency-based education models, there is still an important role for the use
      of multiple choice questions (MCQs) in the assessment of health professionals.
      The challenge, however, is to ensure that MCQs are developed in a way to allow
      educators to derive meaningful information about examinees' abilities. As
      educators' needs for high-quality test items have evolved so has our approach to
      developing MCQs. This evolution has been reflected in a number of ways including:
      the use of different stimulus formats; the creation of novel response formats;
      the development of new approaches to problem conceptualization; and the
      incorporation of technology. The purpose of this narrative review is to provide
      the reader with an overview of how our understanding of the use of MCQs in the
      assessment of health professionals has evolved to better measure clinical
      reasoning and to improve both efficiency and item quality.

PMID- 30299197
TI  - Twelve Tips for Developing Clinical Reasoning Skills in the Pre-Clinical and
      Clinical Stages of Medical School.
AB  - Clinical reasoning (CR) is a complex skill required in future clinicians. The
      best way to develop CR has not been fully elucidated in existing literature.
      Barriers to CR development include content, environmental, and teacher or expert
      physician factors. We have reviewed literature, interviewed medical students and
      teaching staff at the University of Nottingham, and evaluated our teaching
      delivery. We identified twelve strategies to combat barriers to CR learning at
      our university. The foundation for CR must be built early through lectures and
      case-based learning. We emphasize the irreplaceable nature of ward-based learning
      and add on methods of optimizing time on wards. Placement on acute wards with
      trained teaching staff to facilitate CR teaching was suggested. Ward time should
      be supplemented with symptom-focused teaching, patient workshops, simulation
      sessions, virtual case banks, and clinical skills practice. However, ward time is
      the utmost priority and must not be replaced.

PMID- 30299198
TI  - Epicatechin Supplementation and Resistance Training-Induced Improvement of Muscle
      Strength and Circulatory Levels of Plasma Follistatin and Myostatin in Sarcopenic
      Older Adults.
AB  - To investigate the effects of resistance training and Epicatechin supplementation
      on muscle strength, follistatin and myostatin in sarcopenic older adults, 62
      sarcopenic males (68.63+/-2.86 years) underwent a supervised 8-week randomized
      controlled trial. Participants were divided into Resistance Training (RT),
      Epicatechin (EP), Resistance Training+Epicatechin (RT+EP), and Placebo (PL) in a
      double-blind method. A pretest and posttest measurement was conducted. One-way
      ANOVA was used to analyze between-group differences. Significantly greatest
      increase was observed in follistatin, follistatin/myostatin ratio, leg-press, and
      chest-press in RT+EP comparing RT, EP and, PL groups whereas, myostatin decreased
      significantly only in RT+EP and RT groups, however, appMMI and TUG enhanced
      significantly in all experimental groups than the PL group (P<=0.05).
      Consequently, by comparing the results between three experimental groups, the
      greatest improvement was detected in RT+EP group. Therefore, using two
      interventions simultaneously seems to have better impacts on improving muscle
      growth factors and preventing the progression of sarcopenia.

PMID- 30299199
TI  - Stress Relaxation and Targeted Nutrition to Treat Patellar Tendinopathy.
AB  - Patellar tendinopathy is one of the most common afflictions in jumping sports.
      This case study outlines the rehabilitation of a professional basketball player
      diagnosed by MRI with a central core patellar tendinopathy within the proximal
      enthesis. The player undertook a nutrition and strength based rehabilitation
      program combining gelatin ingestion and heavy isometric loading of the patella
      designed to produce significant stress relaxation as part of their competition
      schedule and a whole body training plan. On follow up one and a half years into
      the program an independent orthopedic surgeon declared the tendon normal on MRI.
      Importantly, the improved MRI results were associated with a decrease in pain and
      improved performance. This case study provides evidence that a nutritional
      intervention combined with a rehabilitation program that uses stress relaxation
      can improve clinical outcomes in elite athletes.

PMID- 30299200
TI  - The Magnitude of Rapid Weight Loss and Rapid Weight Gain in Combat Sport Athletes
      Preparing for Competition: A Systematic Review.
AB  - Combat sport athletes typically engage in a process called making-weight,
      characterised by rapid weight loss (RWL) and subsequent rapid weight gain (RWG)
      in the days preceding competition. These practices differ across each sport, but
      no systematic comparison of the size of the changes in body mass exists. The aim
      was to determine the magnitude of RWL and RWG in combat sport athletes preparing
      for competition. The review protocol was preregistered with PROSPERO
      [CRD42017055279]. In eligible studies, athletes prepared habitually with a RWL
      period <=7 days preceding competition. An electronic search of EBSCOhost (CINAHL
      Plus, MEDLINE, SPORTDiscus) and PubMed Central was performed to July 2018.
      Sixteen full-text studies (total 4432 participants, 156 female, 4276 male) were
      included, providing data from five combat sports (boxing, judo, mixed martial
      arts (MMA), taekwondo and wrestling). Three studies reported RWL and fourteen
      studies reported RWG. Duration permitted for RWG ranged 3-32 hours. The largest
      changes in body mass occurred in two separate MMA cohorts (RWL 7.4 +/- 1.1kg
      [~10%], RWG 7.4 +/- 2.8kg [11.7 +/- 4.7%]). The magnitude of RWG appears to be
      influenced by the type of sport, competition structure, and recovery duration
      permitted. A cause for concern is the lack of objective data quantifying the
      magnitude of RWL. There is insufficient evidence to substantiate the use of RWG
      as a proxy for RWL, and little data are available in females. By engaging in RWG,
      athletes are able to exploit rules to compete up to three weight categories
      higher than at the official weigh-in.

PMID- 30299201
TI  - Test-retest reliability of subjective supra-threshold scaling of multiple
      pressure-pain sensations among healthy individuals: a study using hydraulic
      pressure algometry.
AB  - BACKGROUND: Supra-threshold scaling of multiple pressure-pain sensations involves
      delivery of varied stimulus intensities, either via stimulus-dependent or
      response-dependent manner, and recording of subjective pain ratings by
      participants. The focus of this study was to determine the intra- and inter
      session reliability of pain intensity and pain unpleasantness ratings related to
      pressure-pain thresholds (PPTs) of just noticeable pain (JNP), weak pain (WP) and
      moderate pain (MP) among healthy individuals. METHODS: Fourteen healthy
      participants (eight women, six men) participated in three sessions of testing at
      varied intervals over the course of 72 h. In session one, a multiple random
      staircase method using hydraulic pressure algometry was used to measure PPT of
      JNP, WP and MP on thumbnail bed. In session 2, ratings of pain intensity and pain
      unpleasantness were recorded when stimuli at levels corresponding to PPT of JNP,
      WP and MP were repeatedly applied before and after 20 min of no intervention.
      RESULTS: Interclass correlation coefficient (ICC) values for pain ratings of JNP,
      WP and MP in intra-session reliability were 0.810, 0.826 and 0.881, respectively,
      whereas the values were 0.817, 0.792 and 0.910, respectively, for inter-session
      reliability. ICC values for pain unpleasantness were also highly consistent and
      repeatable. Temporal summation of pain intensity and pain unpleasantness were not
      related to the repeated application of pressure stimuli. CONCLUSIONS: The
      findings indicate that the pain intensity and pain unpleasantness ratings for
      stimuli at levels equal to the thresholds of JNP, WP and MP have good intra- and
      inter-session reliability. SIGNIFICANCE: This study showed that both pain
      intensity and pain unpleasantness of JNP, WP and MP have good intra- and inter
      session reliability and agreement. Furthermore, the temporal summation of pain or
      unpleasantness is not related to repeated application of pressure stimuli.
      ABBREVIATIONS: JNP: Just noticeable pain; WP: Weak pain; MP: Moderate pain; PPTs:
      pressure-pain thresholds; HPA: Hydraulic pressure algometry; MRSM: multiple
      random staircase method.

PMID- 30299202
TI  - Long-Term Safety and Efficacy of Weekly Subcutaneous Tocilizumab Monotherapy in
      Patients With Rheumatoid Arthritis Who Had an Inadequate Response to Subcutaneous
      Tocilizumab Every Other Week: Results From the Open-Label Extension of the
      SHINOBI Study.
AB  - OBJECTIVE: To evaluate the long-term safety and efficacy of subcutaneous
      tocilizumab (TCZ-SC) monotherapy administered weekly (qw) in patients with
      rheumatoid arthritis who had an inadequate response to TCZ-SC every other week
      (q2w). METHODS: Patients who completed 12 weeks of double-blind treatment with
      either TCZ-SC q2w monotherapy or TCZ-SC qw monotherapy were switched to or
      continued to receive open-label treatment with TCZ-SC qw monotherapy for 40
      weeks. Safety and efficacy were assessed. Subgroup analyses of Disease Activity
      Score based on 28 joints using erythrocyte sedimentation rate (DAS28-ESR) were
      performed at 12 weeks. RESULTS: The incidence of adverse events was 464.4/100
      patient-years (PY). The incidence of infection was 121.3/100 PY. The safety
      profile of TCZ-SC qw monotherapy was consistent with that of prior studies of
      TCZ. No additional safety concerns were observed. Improvement from baseline in
      DAS28-ESR was maintained at week 52 in patients who continued TCZ-SC qw and
      improved in patients who switched from TCZ-SC q2w to qw. At week 12, the efficacy
      of TCZ-SC qw monotherapy was greater than that of TCZ-SC q2w monotherapy
      irrespective of weight and BMI subgroups. CONCLUSION: The long-term weekly dosing
      of TCZ-SC monotherapy was well tolerated and efficacy was maintained over 52
      weeks.

PMID- 30299203
TI  - Antioxidative Effects of Piperine against Cadmium-Induced Oxidative Stress in
      Cultured Human Peripheral Blood Lymphocytes.
AB  - Cadmium (Cd) has a remarkable property of generating oxidative stress. It
      upregulates the level of reactive oxygen species, which generates damage to
      lipids, proteins, and DNA The level of oxidative stress by Cd is observed by
      inhibitory effects of antioxidant enzymes such as catalase, superoxide dismutase,
      glutathione reductase, and glutathione peroxidase. Piperine is one of the plant
      derived alkaloids isolated from Piper nigrum and Piper longum. It diminishes the
      level of oxidative damage by quenching the free radicals and reactive oxygen
      species and inhibiting the lipid peroxidation. It is well known to induce stress
      proteins, including metallothionein (MT), a metal-binding protein and heat shock
      protein (HSP70). In the present work, antioxidative effects of piperine have been
      studied against Cd-induced oxidative stress. We observed its ameliorative effects
      using various biomarkers, such as comet and lipid peroxidation (LPA) assays in
      cultured human peripheral blood lymphocytes from healthy individuals. Piperine at
      35 and 50 uM concentrations significantly reduces the tail moment and
      peroxidation of lipids. We also explored the relationship of MT2A gene
      polymorphism on oxidative and antioxidative effects of Cd and piperine,
      respectively. At selected concentration, we observed a decrease in the mean value
      of tail moment and lipid peroxidation level. However, the overall effect was
      statistically nonsignificant (p > .05).

PMID- 30299204
TI  - Twelve tips for clinicians dealing with uncertainty when assessing learners.
AB  - Clinician educators often experience distress caused by uncertainty regarding how
      effectively to participate in assessment practices in a way that supports both
      their programs and their students. Uncertainty is a common state for clinicians,
      particularly for those who see patients with early or ill-defined illness
      presentations. While clinicians often feel ill at ease when facing uncertainty in
      the clinical realm, becoming comfortable with uncertainty and learning to manage
      such states are now recognized as vital components of clinical practice.
      Clinicians, as a result, have adopted a series of strategies to lessen the unease
      that uncertainty can create. While similar experiences plague clinician educators
      placed in assessment roles, much less attention has been given to how we can
      support individuals in the education setting. Here, the distress of uncertainty
      may be greater due to clinician educators having less experience with assessment
      practices. Fortunately, strategies that are effective in the clinical domain can
      be translated into the assessment realm to accommodate uncertainty when assessing
      learners. In this 12 tips article we offer guidance on the translation of such
      strategies.

PMID- 30299206
TI  - Physical Activity Attitudes, Preferences, and Experiences of Regionally-Based
      Australia Adults 65+ Years.
AB  - An understanding of physical activity attitudes, preferences, and experiences in
      older adults is important for informing interventions. Focus groups were
      conducted with 46 regionally-based Australian adults aged 65 years and older who
      were not currently meeting activity recommendations. Content analysis revealed
      that participants mainly engaged in incidental activities such as gardening and
      household chores rather than planned exercise; however, leisure time walking was
      also mentioned frequently. While participants valued the physical and mental
      health benefits of physical activity, they reported being restricted by poor
      physical health, extreme weather and fear of injury. Participants were interested
      in exercise groups and physical activity programs tailored to their existing
      physical health. The majority of participants reported preferring to be active
      with others. The findings from this study are useful in for informing future
      interventions specifically tailored to the needs of older adults in Australia.

PMID- 30299207
TI  - Human amniotic membrane as differentiating matrix for in vitro chondrogenesis.
AB  - AIM: The aim of the present study is to use human amniotic membrane (HAM) for in
      vitro chondrogenesis of placenta-derived mesenchymal stem cells (MSCs) and
      umbilical cord-derived MSCs. MATERIALS & METHODS: MSCs from the placenta and
      umbilical cord were isolated, characterized by immunophenotyping and after
      analyzing their rate of proliferation, cytotoxicity and viability, chondrogenesis
      was performed on plastic adherent surface and on HAM. RESULTS: Successfully
      isolated and characterized placenta-derived MSCs and umbilical cord-derived MSCs
      revealed positive expression of MSCs markers CD90, CD73, CD105 and CD49d, while
      they were negative for CD45. Both types of cells in the presence of chondrogenic
      induction medium on plastic adherent surface and HAM showed aggregates of
      proteoglycan and strong expression of COL2A1 (collagen 2) and ACAN1 (aggrecan).
      CONCLUSION: HAM supported proliferation as well as chondrogenesis of MSCs and
      provide novelty of HAM utilization as an efficient natural delivery matrix for
      stem cell transplantation.

PMID- 30299205
TI  - Integration of genomics, high throughput drug screening, and personalized
      xenograft models as a novel precision medicine paradigm for high risk pediatric
      cancer.
AB  - Pediatric high grade gliomas (HGG) are primary brain malignancies that result in
      significant morbidity and mortality. One of the challenges in their treatment is
      inter- and intra-tumoral heterogeneity. Precision medicine approaches have the
      potential to enhance diagnostic, prognostic and/or therapeutic information. In
      this case study we describe the molecular characterization of a pediatric HGG and
      the use of an integrated approach based on genomic, in vitro and in vivo testing
      to identify actionable targets and treatment options. Molecular analysis based on
      WGS performed on initial and recurrent tumor biopsies revealed mutations in TP53,
      TSC1 and CIC genes, focal amplification of MYCN, and copy number gains in SMO and
      c-MET. Transcriptomic analysis identified increased expression of MYCN, and genes
      involved in sonic hedgehog signaling proteins (SHH, SMO, GLI1, GLI2) and receptor
      tyrosine kinase pathways (PLK, AURKA, c-MET). HTS revealed no cytotoxic efficacy
      of SHH pathway inhibitors while sensitivity was observed to the mTOR inhibitor
      temsirolimus, the ALK inhibitor ceritinib, and the PLK1 inhibitor BI2536. Based
      on the integrated approach, temsirolimus, ceritinib, BI2536 and standard therapy
      temozolomide were selected for further in vivo evaluation. Using the PDX animal
      model (median survival 28 days) we showed significant in vivo activity for mTOR
      inhibition by temsirolimus and BI2536 (median survival 109 and 115.5 days
      respectively) while ceritinib and temozolomide had only a moderate effect (43 and
      75.5 days median survival respectively). This case study demonstrates that an
      integrated approach based on genomic, in vitro and in vivo drug efficacy testing
      in a PDX model may be useful to guide the management of high risk pediatric brain
      tumor in a clinically meaningful timeframe.

PMID- 30299208
TI  - Sensitivity of Botrytis cinerea From Nectarine/Cherry in China to Six Fungicides
      and Characterization of Resistant Isolates.
AB  - Botrytis cinerea, the causal agent of gray mold, can result in considerable
      preharvest and postharvest losses in many economically valuable plant species.
      Fungicides were widely used to minimize such losses, but fungicide resistances
      were detected frequently. In the present study, we collected 164 isolates from
      nectarine and cherry in China and tested the sensitivity to six fungicides. Among
      the tested isolates, 71 (43.3%) were resistant to azoxystrobin, 14 (8.5%) to
      cyprodinil, 7 (4.3%) to boscalid, 4 (2.4%) to carbendazim, 1 (0.6%) to iprodione,
      and no isolates were found to be resistant to fludioxonil. The EC50 value and
      resistance factor (RF) of resistant isolates were determined. Fitness analysis
      showed that there were no significant differences between sensitive and resistant
      isolates for osmotic stress and pathogenicity, while more conidia production was
      observed for some resistant isolates. Control efficacy of fungicides showed that
      the resistant isolates could not be controlled efficiently by using corresponding
      fungicides. The point mutation G143A was detected in the Cyt b gene of the
      isolates resistant to azoxystrobin, while the point mutation H272R of SdhB gene
      was confirmed in boscalid-resistant isolates, and mutations E198V/A of TUB2 gene
      and mutation I365S of BcOs1 occurred in carbendazim-resistant and iprodione
      resistant isolates, respectively. These results indicate that the occurrence of
      fungicide resistance greatly threatens the management of gray mold on stone
      fruits nectarine and cherry.

PMID- 30299209
TI  - Global role for coactivator complexes in RNA polymerase II transcription.
AB  - SAGA and TFIID are related transcription complexes, which were proposed to
      alternatively deliver TBP at different promoter classes. Recent genome-wide
      studies in yeast revealed that both complexes are required for the transcription
      of a vast majority of genes by RNA polymerase II raising new questions about the
      role of coactivators.

PMID- 30299210
TI  - Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes
      a Krebs cycle intermediate (SDH) in an animal model.
AB  - Rabies is the most lethal zoonotic, vaccine-preventable viral disease in the
      world. Its treatment is complicated by insufficient vaccine supply and the
      requirement for four to five repeated injections, as commercially available
      inactivated rabies lack adjuvant and have low immunogenicity. In this study, we
      focused on the role of a Krebs cycle intermediate, succinate dehydrogenase (SDH),
      in the innate immune response to cytokine production. We formulated a novel
      nanoemulsion adjuvant, Golden03, which stabilizes mouse SDH activity and contains
      more coenzyme Q10 and succinic acid than the classic MF59 adjuvant. Mice were
      immunized on days 1, 3, and 7, with seroconversion rate results suggesting that
      Golden03 significantly enhanced vaccine-stimulated antibody production against
      the rabies virus. Neutralizing antibody concentration testing by RFFIT indicated
      that treatment with Golden03 could result in antibody levels of up to 0.74 IU/mL
      5 days post infection (DPI). ELISPOT for IFN-gamma in mouse spleen cells showed
      that Golden03 enhanced immune responses at 14 DPI, inducing a rapid and powerful
      cellular response compared to the control group. Furthermore, the Vaccine
      Golden03 group displayed no obvious weight loss or death after intracranial
      injection with CVS-11. An additional advantage is that Golden03 allowed for a
      three-quarter reduction in dose, while maintaining its efficacy and rapid
      stimulation effect. We suggest that Golden03 could be developed as a potential
      adjuvant for use in human rabies vaccine.

PMID- 30299211
TI  - MiRNA-155 regulates lymphangiogenesis in natural killer/T-cell lymphoma by
      targeting BRG1.
AB  - BACKGROUND: miR-155 was up-regulated in natural killer/T-cell lymphoma (NKTCL),
      an aggressive malignancy, and correlated with disease progression. However,
      minimal is known on biological activities and underlying mechanisms of miR-155 in
      NKTCL. In this study, we examined BRG1, a potential target of miR-155, and
      focused on the miR-155/BRG1 signaling in regulating lymphangiogenesis of NKTCL.
      METHODS: The expression of miR-155, BRG1, VEGFC, and VEGFD was compared between
      two NKTCL cell lines and normal NK cells. The critical role of miR-155 and STAT3
      was assessed using miR-155 inhibitor and STAT3 inhibitor S31-201, respectively.
      Two biological phenotypes, apoptosis and pro-lymphangiogenesis, were examined in
      vitro by flow cytometry and lymphatic tube formation, respectively, and in vivo
      using an NKTCL xenograft model. RESULTS: The miR-155 level negatively correlated
      with BRG1, but positively with VEGFC in normal NK as well as two NKTCL cell
      lines. Targeting miR-155 in NKTCL cells significantly boosted BRG1 expression and
      decreased the activated STAT3 or VEGFC level, leading to enhanced apoptosis and
      reduced lymphangiogenesis. STAT3 acted downstream of BRG1 and essentially
      regulated miR-155-mediated up-regulation of VEGFC and pro-lymphangiogenesis. In
      vivo, targeting miR-155 inhibited primary xenograft growth as well as tumor
      associated lymphangiogenesis. CONCLUSIONS: By inhibiting BRG1 expression, miR-155
      activated STAT3/VEGFC signaling and promoted lymphangiogenesis. In addition, miR
      155 also controlled the viability of NKTCL cells. Therefore, targeting miR-155
      provides a novel therapy for NKTCL.

PMID- 30299212
TI  - Reasons for attempting suicide: An exploratory study in Ghana.
AB  - This study examined the reasons for suicide attempts among patients in Ghana.
      Semi-structured interviews were conducted among 30 informants who had been
      hospitalized for attempted suicide. Interpretative Phenomenological Analysis
      (IPA) was used to analyse the transcribed narratives, and five main themes
      emerged: 1) lack of support; 2) abandonment; 3) shame; 4) existential struggles;
      and 5) supernatural reasons. There were gender differences with abandonment
      reported by only women and shame associated with economic difficulties reported
      only by men. Findings are discussed within the context of a socio-cultural theory
      of suicide behaviour, and implications for the prevention of suicide and care of
      suicidal persons are suggested.

PMID- 30299213
TI  - Regulation of Plant Immune Signaling by Calcium-Dependent Protein Kinases.
AB  - Activation of Ca2+ signaling is a universal response to stress that allows cells
      to quickly respond to environmental cues. Fluctuations in cytosolic Ca2+ are
      decoded in plants by Ca2+-sensing proteins such as Ca2+-dependent protein kinases
      (CDPKs). The perception of microbes results in an influx of Ca2+ that activates
      numerous CDPKs responsible for propagating immune signals required for resistance
      against disease-causing pathogens. This review describes our current
      understanding of CDPK activation and regulation, and provides a comprehensive
      overview of CDPK-mediated immune signaling through interaction with various
      substrates.

PMID- 30299214
TI  - Influence of deployment time and surface wind speed on the accuracy of
      measurements of greenhouse gas fluxes using a closed chamber method under low
      surface wind speed.
AB  - As a convenient method, the closed chamber method has been applied to determine
      gaseous emission fluxes from fully open animal feeding operations despite the
      measured fluxes being theoretically affected by deployment time, wind speed over
      the emitting surface and detected gas mass. This laboratory study evaluated the
      effects of deployment time (0 to 120 min) and external surface wind speed (ESWS)
      (0.00, 0.25, 0.50, 0.75, 1.00, 1.50 and 2.00 m sec-1) on the measurement accuracy
      of a 300 mm (diameter) * 400 mm (height) (D300*H400) closed chamber using methane
      (CH4), nitrous oxide (N2O) and sulfur hexafluoride (SF6) as reference gases. The
      results showed that the overall deviation ratio between the measured and
      reference CH4 fluxes ranged from 9.99 % to -37.32 % and the flux was
      overestimated in the first 20 min. The measured N2O and SF6 emissions were
      smaller than the reference fluxes using the chamber. N2O measurement accuracy
      decreased from -14.47 to -35.09% with deployment time extended to 120 min, while
      SF6 accuracy sharply increased in the first 40 min, with the deviation
      stabilizing at approximately -5.00%. CH4, N2O and SF6 measurements were
      significantly affected by deployment time and ESWS (P<0.05), and the interaction
      of those two factors greatly influenced CH4 and SF6 measurements (P<0.05). With
      the D300*H400 closed chamber, deployment times of 20 to 30 min and 10 to 20 min
      are recommended to measure CH4 and N2O, respectively, from the open operations of
      dairy farms under wind speeds lower than 2 m sec-1. Implications: This study
      recommended the suitable deployment times and wind speeds for using a D300 * H400
      closed chamber to measure CH4, N2O, and SF6 in an open system, such as a dairy
      open lot and manure stockpile, to help researchers and other related industry
      workers get accurate data for gas emission rate. Deployment times of 20 to 30 min
      and 10 to 20 min were recommended to measure CH4 and N2O emissions using the D300
      * H400 closed chamber, respectively, from the open operations of dairy farms
      under wind speeds lower than 2 m sec-1. For the measurement of SF6, a typical
      tracer gas, a deployment of 70 to 90 min was suggested.

PMID- 30299215
TI  - Pulmonary adverse events related to idelalisib therapy: A single centre
      experience.
AB  - Idelalisib is a potent and selective inhibitor of the PI3Kdelta approved since
      September 2014 for the treatment of several types of B cell malignancies.
      Pulmonary adverse events related to idelalisib are an emerging serious adverse
      event. We report here a single centre cohort of 16 patients who initiated
      idelalisib as routine treatment. Five of them experienced severe pulmonary
      adverse events related to idelalisib therapy. Comparison of the 5 patients with
      severe pulmonary events versus the 11 patients without identified no predisposing
      factors. Severe pulmonary adverse events were related to infectious pneumonia
      and/or to a drug-induced pneumonitis. The mechanisms of idelalisib-associated
      pneumonitis are unknown but consistent with the drug-induced pneumonitis
      described with mTOR inhibitors. Indeed, by inhibiting PI3Kdelta, idelalisib also
      inhibits the mTOR pathway. Clinicians should be aware that any idelalisib-treated
      patient who presents with pulmonary symptoms should be evaluated for pneumonitis.
      Corticosteroids should be considered in addition to anti-infective therapy in
      case of severe pneumonitis or persistent pulmonary symptoms despite adequate
      antibiotic therapy.

PMID- 30299216
TI  - Augmentation cystoplasty in neuropathic bladder.
AB  - OBJECTIVES: To look at the changing role of cystoplasty in the neuropathic
      population. DESIGN: Retrospective case series. SETTING: Single center over a 10
      year period from 2004 to 2014. PARTICIPANTS AND INTERVENTION: In 1995, the
      Princess Royal spinal injuries unit published the outcomes of 78 neuropathic
      patients who had undergone cystoplasty in the 10-year period from 1982 to 1992.
      [Singh G, Thomas DG. Enterocystoplasty in the neuropathic bladder. Neurourol
      Urodyn 1995; 14(1): 5-10.]. In this series, we review 51 consecutive patients
      undergoing the same operation over a 10-year period from 2004 to 2014 in the same
      single unit. OUTCOME MEASURES: Demographic data were collected to include patient
      age, condition, and previous treatments. Pre- and post-operative details included
      sphincter insertions, renal function, continence rates, and complications.
      RESULTS: Despite an increase in the number of patients seen at the unit, there
      were considerably fewer cystoplasty procedures performed in the current series
      (51 vs. 78 in the 1982-1992 series). There were also significantly fewer patients
      with spina bifida and fewer concomitant sphincter insertions in the latter series
      (eight patients vs. 52 in the 82/92 series). Nevertheless, similar outcomes are
      observed between the current and 1982-1992 series, with continence rates of 93.7
      and 93.6%, respectively and low numbers of reported adverse events for both
      retrospective cohorts. CONCLUSIONS: Cystoplasty remains a safe and effective
      option for the management of neuropathic bladder in a carefully selected group of
      patients.

PMID- 30299217
TI  - The impact of canister geometry on chemical biological radiological and nuclear
      filter performance: A computational fluid dynamics analysis.
AB  - Steady-state axisymmetric simulations using the Reynolds-Averaged Navier-Stokes
      equations have been carried out in order to optimize the performance of a
      Chemical, Biological, Radiological and Nuclear (CBRN) canister filter for its use
      in a powered air-purifying respirator (PAPR). Alterations have been made to the
      shape of the canister, the spacing of the rear wall of the canister with regard
      to the carbon filter, and the bracketing between (i) the particulate filter and
      the carbon bed and (ii) the carbon bed and the canister wall. The pressure drop
      across the canister and the residence time distribution at the rear of the carbon
      bed have been analysed in detail based on an extensive parametric analysis
      involving the aforementioned variations. It has been demonstrated that the non
      uniform porosity profile of the carbon bed resulted in alternating regions of
      high and low velocity close to the canister wall, providing a possible route for
      breakthrough. Designs, which included a bracket at the rear of the carbon bed,
      blocked this route and consequently had a longer minimum mean residence time than
      those, which did not. It has also been shown that the spacing between the carbon
      bed and the canister rear wall had a large impact on both residence time and
      pressure drop. In cases where the carbon backed directly onto the canister rear
      wall flow in the axial direction from the outside wall towards the canister axis
      resulted in far greater pressure drop and a reduction in minimum mean residence
      time within the carbon bed.

PMID- 30299218
TI  - The Ongoing Sodium Controversy - Between PURE and NutriCode.
AB  - The impact of sodium intake on cardiovascular health has long been a subject of
      controversial debates. On the one hand, the World Health Organization (WHO) and
      the American Heart Association (AHA) have argued for a target of 1500-2000 mg of
      sodium per day (4-5 g sodium chloride daily). On the other hand, this
      recommendation has been accompanied by a growing body of criticism. Recently, the
      results of the PURE and the NutriCode study have flared up the "salt
      controversy". Actually, the results of the PURE study seem to strengthen the
      position of those who have called into question the AHA and WHO guidelines for
      daily sodium intake whereas those who recommend a considerable salt reduction
      believe that the NutriCode study confirm their conviction. In this paper, the
      results of the PURE and NutriCode study will be discussed and evaluated with
      regard to practical consequences.

PMID- 30299219
TI  - Analysis on the risks of severe adverse events in rabies post-exposure
      prophylaxis and appropriate decision-making procedure.
AB  - Severe adverse events (AEs) following post-exposure rabies vaccination had been
      occasionally described in previous studies. Once AEs occurred, immediate medical
      treatment and appropriate change of vaccine and vaccination schedule were of
      significance. It was also important and challengeable to determine the
      relationship among adverse reactions, vaccines residues and laboratory tests for
      patients, to choose a proper vaccine in resumed vaccination, to avoid the
      reoccurrence of AEs and to ensure adequate immune response. Here, we present
      steps about how to cope with AEs by giving an example with a two-year-old girl
      who was identified as category II exposure to rabies, suffered from anaphylaxis
      after first dose administration with human diploid rabies vaccine (HDCV) so
      vaccination was temporarily suspended. Dexamethasone was prescribed to her in
      anti-allergy therapy. Allergy tests indicated that the patient was not sensitive
      to allergens and heterologous proteins. Vaccine test report showed that residual
      kanamycin existed in that batch of vaccines. This reminded us to provide her
      antibiotic skin sensitivity test which found she was allergic to kanamycin. Thus,
      we could conclude it was the cause of AEs. Then, 0.5 mL lyophilized Purified Vero
      Cell Rabies Vaccine (PVRV) without any residues was enrolled in the resumed
      vaccination. To ensure successful immunization, immunogenicity test was also
      provided which showed adequate immune response (RVNA >= 0.5 IU/mL) starting from
      day14. Besides, no further AEs occurred afterward. This study emphasized the
      importance of in-depth survey, analysis and implied the necessity to
      scientifically and properly choose the optimal vaccine for patients and
      appropriately provide treatments if AEs occurred.

PMID- 30299220
TI  - Achieving high HPV vaccine completion rates in a pediatric clinic population.
AB  - OBJECTIVE: To evaluate the efficacy of an intervention utilizing patient
      navigators (PNs) to 1) educate families on human papillomavirus (HPV) vaccination
      in a clinic setting and 2) provide personalized reminders for follow-up. METHOD:
      Families with 9-17 year-old children who had no record of completing the HPV
      vaccination series receiving primary or specialty care in 3 pediatric clinics
      were approached by PNs between February 1, 2015 and August 31, 2016. Demographic
      characteristics, visit type, preferred contact method, rates and correlates of
      completion, and appointments missed were analyzed. In addition, qualitative
      interviews of 21 providers and PNs assessed their perceptions of the program.
      RESULTS: 1,391 adolescents were identified out of 2,162 patients approached as
      unvaccinated or partially vaccinated prior starters; among the unvaccinated, 930
      received the 1st dose after being counseled by the PN (66.9%), either immediately
      or at a follow-up visit soon thereafter. This included 118 siblings of patients
      who did not have an appointment that day. Of initiators approached between
      2/1/2015 and 8/31/2016, 93% (864/930) completed the series by 8/31/2017. No
      differences in series completion among initiators were observed by gender or
      race/ethnicity, but older patients (15-17 years old) were less likely to complete
      than 11-12 year olds. Of the 688 patients identified as prior starters, 85%
      completed the series through the program. Qualitative interviews demonstrated
      that providers felt the program addressed major barriers to HPV vaccination.
      CONCLUSION: Employing PNs dramatically increased HPV vaccine series completion
      among boys and girls with historically low HPV vaccination rates at pediatric
      clinics in Texas. Clinic providers felt this program addressed many barriers they
      observed prior to program implementation. This approach could markedly improve
      HPV vaccine series completion rates in the US.

PMID- 30299221
TI  - New ways to get policy into practice.
AB  - PURPOSE: Health service effectiveness continues to be limited by misaligned
      objectives between policy makers and frontline clinicians. While capturing the
      discretion workers inevitably exercise, the concept of "street-level bureaucracy"
      has tended to artificially separate policy makers and workers. The purpose of
      this paper is to understand the role of social-organizational context in aligning
      policy with practice. DESIGN/METHODOLOGY/APPROACH: This mixed-method
      participatory study focuses on a locally developed tool to implement an Australia
      wide strategy to engage and respond to mental health services for parents with
      mental illness. Researchers: completed 69 client file audits; administered 64
      staff surveys; conducted 24 interviews and focus groups (64 participants) with
      staff and a consumer representative; and observed eight staff meetings, in an
      acute and sub-acute mental health unit. Data were analyzed using content
      analysis, thematic analysis and descriptive statistics. FINDINGS: Based on
      successes and shortcomings of the implementation (assessment completed for only
      30 percent of clients), a model of integration is presented, distinguishing
      "assimilist" from "externalist" positions. These depend on the degree to which,
      and how, the work environment affords clinicians the setting to coordinate
      efforts to take account of clients' personal and social needs. This was
      particularly so for allied health clinicians and nurses undertaking sub-acute
      rehabilitative-transitional work. ORIGINALITY/VALUE: A new conceptualization of
      street-level bureaucracy is offered. Rather than as disconnected, it is a process
      of mutual influence among interdependent actors. This positioning can serve as a
      framework to evaluate how and under what circumstances discretion is appropriate,
      and to be supported by managers and policy makers to optimize client-defined
      needs.

PMID- 30299222
TI  - What's the fuss? Gender and academic leadership.
AB  - PURPOSE: Women continue to be disproportionately represented in top leadership
      positions. Leadership development programs typically focus on skills attainment.
      The purpose of this paper is to explore the perceptions and experiences of
      academic leaders in order to inform how leadership development programs may more
      effectively address the gender gap in leadership. DESIGN/METHODOLOGY/APPROACH: A
      sequential mixed methods study design was used. Participants completed the
      Leadership Practice Inventory (r)(LPI) survey followed by individual interviews
      of a subset of participants. The survey results were analyzed and compared by
      gender using the t-test. Thematic analysis was used to compare themes across and
      between genders. Quantitative and qualitative findings were integrated in the
      final analysis. FINDINGS: In total, 65 leaders (38 women; 27 men) (37.7 percent
      response rate) participated in the survey. There were no significant demographic
      or statistical differences between women and men on any of the LPI(r) components.
      Five women and five men were interviewed. Thematic analysis revealed common
      leadership aspirations and values. Gender differences were noted in leadership
      attainment, mentorship and the influence of gender on leadership. While the male
      narratives reflected cognitive awareness of gender inequities, the female
      narratives also included lived experiences. Male participants focused on the
      importance of meritocracy whereas the female participants emphasized the gendered
      social and structural influences on leadership attainment. PRACTICAL
      IMPLICATIONS: Leadership development programs need go beyond generic "skills
      building" in order to conceptualize leadership within a gendered social context.
      This framework will enable critical awareness and tools for developing both women
      and men's fullest leadership potential. ORIGINALITY/VALUE: This study was
      conducted in order to better understand how academic health leaders experience
      the intersection of gender and leadership. The findings contribute to the current
      literature by providing insight into perceptual gaps that exist at the level of
      practice between women and men leaders. In doing so, the authors discuss how
      leadership development programs may play a more effective role in addressing
      gender equity in leadership.

PMID- 30299223
TI  - Team based communication and the healthcare communication space.
AB  - PURPOSE: While previous studies have described structural, process and social
      aspects of the healthcare communication space there is no overall model of it.
      Such a model is an essential first step to improving the operationalization and
      management of healthcare communication. The paper aims to discuss these issues.
      DESIGN/METHODOLOGY/APPROACH: This paper used a case study approach to study team
      based communication on a palliative care unit. Non-participant observation,
      interviews and documents were analyzed using qualitative content analysis.
      FINDINGS: The analysis developed an overall model of the healthcare communication
      space that consists of five stages: purpose, practices and workflows, structures,
      implementation, and the development of common ground to support team-based
      communication. The authors' findings emphasized that implicit communication
      remains a predominant means of communication and workflow issues at the
      individual level are a frequent cause of unnecessary group communication tasks.
      ORIGINALITY/VALUE: To improve team-based communication we first need to develop
      protocols that support team communication needs such as loop closing of group
      communication tasks in order to minimize unnecessary individual communication
      tasks. We also need to develop common ground at the protocol, document and
      terminology levels as part of supporting team-based communication.

PMID- 30299224
TI  - Discursive practice - lean thinking, nurses' responsibilities and the cost to
      care.
AB  - PURPOSE: The purpose of this paper is to explore the literature regarding work
      intensification that is being experienced by nurses, to examine the effects this
      is having on their capacity to complete care. The authors contend that nurses'
      inability to provide all the care patients require, has negative implications on
      their professional responsibility. DESIGN/METHODOLOGY/APPROACH: The authors used
      institutional ethnography to review the discourse in the literature. This
      approach supports inquiry through the review of text in order to uncover
      activities that remain institutionally accepted but unquestioned and hidden.
      FINDINGS: What the authors found was that the quality and risk management forms
      an important part of lean thinking, with the organisational culture influencing
      outcomes; however, the professional cost to nurses has not been fully explored.
      RESEARCH LIMITATIONS/IMPLICATIONS: The text uncovered inconsistency between what
      organisations accepted as successful cost savings, and what nurses were
      experiencing in their attempts to achieve the care in the face of reduced time
      and human resources. Nurses' attempts at completing care were done at the risk of
      their own professional accountability. PRACTICAL IMPLICATIONS: Nurses are working
      in lean and stressful environments and are struggling to complete care within
      reduced resource allocations. This leads to care rationing, which negatively
      impacts on nurses' professional practice, and quality of care provision.
      ORIGINALITY/VALUE: This approach is a departure from the standard qualitative
      review because the focus is on the textual relationships between what is being
      advocated by organisations directing cost reduction and what is actioned by the
      nurses working at the coalface. The discordant standpoints between these two
      juxtapositions are identified.

PMID- 30299225
TI  - Darzi Clinical Leadership Fellows: an activity theory perspective.
AB  - PURPOSE: The purpose of this paper is to review the impact of the clinical
      leadership programme, in enabling the Darzi fellows to lead change projects in
      health and care services, and to secure quality healthcare in the NHS beyond the
      lifetime of the programme. DESIGN/METHODOLOGY/APPROACH: A longitudinal empirical
      investigation of clinical leaders ( n=80) over an eight-year period was framed
      through an activity theory (AT)-driven research methodology using a mixed-methods
      approach. FINDINGS: AT illuminated how change was sustained in the NHS in London
      through the Darzi Clinical Leadership Fellowship. By any reasonable measurement,
      this programme excels, with learning and positive behavioural change sustained
      after the Fellowship across the NHS. Further recognition is needed of the
      continuing development needs of fellows as they take on more responsible
      leadership roles in their careers. RESEARCH LIMITATIONS/IMPLICATIONS: Darzi
      fellows are a hard-to-reach group. The sample represents a response rate of 34
      per cent. In total, 77 per cent of respondents emanated from cohorts 5 to 8
      programmes. PRACTICAL IMPLICATIONS: The investment in a clinical leadership
      programme focused on systems leadership for quality generates value for the NHS.
      SOCIAL IMPLICATIONS: Countless interventions flowed through London's healthcare
      community and beyond as a result of the Fellowship. This research exposed how
      Darzi fellows continue to lead innovation for alternative healthcare outcomes.
      Many proactive fellows employ a suite of learned skills and capabilities to lead
      systemic change. ORIGINALITY/VALUE: This research is the first known longitudinal
      clinical leadership development study undertaken. The Darzi programme has created
      a unique clinical network of mutually supportive, team-centric systems thinkers
      and doers, with an evidence-based approach to systems change. Many fellows are
      catalysing sustainable change in the healthcare environment.

PMID- 30299226
TI  - Stroke rehabilitation and research: consideration of the role of the cortico
      reticulospinal system.
AB  - A cerebrovascular accident, otherwise known as stroke, has the potential to
      damage multiple areas within the brain affecting descending motor control via a
      multitude of pathways resulting in a wide variety of movement problems. The
      cortico-reticulospinal system, one of the largest motor systems, is frequently
      affected, compromising its output, resulting in postural control deficits. The
      identification of clinically relevant instruments and scales to document and
      evaluate recovery in post-stroke patients is vital. However, the availability of
      such measures and scales which take into consideration the role of postural
      control as an integral component of functional movement performance are scarce.
      This paper will critically discuss the importance of integrating current
      neuroscience and motor control knowledge in order to better understand and
      describe the clinical presentation of persons post-stroke such that the
      effectiveness of stroke rehabilitation can be appropriately measured.

PMID- 30299227
TI  - Early predictors of developing problematic spasticity following traumatic spinal
      cord injury: A prospective cohort study.
AB  - OBJECTIVE: To identify early predictors and develop reliable, validated
      prediction models for development of problematic spasticity after traumatic
      spinal cord injury (SCI). DESIGN: Prospective cohort study of the Rick Hansen
      Spinal Cord Injury Registry (RHSCIR), retrospective review of inpatient medical
      charts. SETTING: Quaternary trauma center, rehabilitation center, community
      settings. PARTICIPANTS: Individuals with traumatic SCI between March 1, 2005, and
      March 31, 2014, prospectively enrolled in the Vancouver site RHSCIR.
      INTERVENTIONS: None. MAIN OUTCOME MEASURE: Spasticity limiting function or
      requiring treatment (problematic spasticity) on the Spinal Cord Injury Health
      Questionnaire. RESULTS: In 350 patients, variables documented during
      hospitalization that predicted the development of problematic spasticity up to 5
      years post-injury included: initial Glasgow Coma Scale; age at time of injury;
      admission to rehabilitation center; community discharge anti-spasticity
      medication prescription, neurological status, Penn Spasm Frequency Scale, and
      pain interference with quality of life, sleep, activities; greater change in AIS
      motor scores between admission and discharge. The predictive models had area
      under the receiver operating characteristic curve of 0.80 (95% CI 0.75, 0.85) in
      the development set (N = 244) and 0.84 (95% CI 0.74, 0.92) in the validation set
      (N = 106) for spasticity limiting function and 0.81 (95% CI 0.76, 0.85) in the
      development set and 0.85 (95% CI 0.77, 0.92) in the validation set for spasticity
      requiring treatment. CONCLUSIONS: Our prediction models provide an early
      prognosis of risk of developing problematic spasticity after traumatic SCI, which
      can be used to improve clinical spasticity management and assist research (e.g.
      risk stratification in interventional trials).

PMID- 30299228
TI  - Detecting lenticulostriate artery lesions in patients with acute ischemic stroke
      using high-resolution MRA at 7 T.
AB  - Background Recent advances in high-resolution (HR) magnetic resonance angiography
      (MRA) using ultrahigh-field systems enable direct visualization of the
      lenticulostriate arteries (LSAs), which had been hardly achieved by conventional
      MRA. Hence, by using HR-MRA at 7 T, we attempted to assess occlusive changes in
      the LSAs in patients with LSA territorial infarcts. Methods We prospectively
      examined 34 consecutive patients with acute ischemic stroke in the LSA territory
      using a 7 T scanner. We measured the lengths of the relevant LSAs on HR-MRA and
      the diameters/volume of the infarcts and compared these between the patients
      with/without occlusive changes in the LSAs. Results On HR-MRA, occlusion of the
      LSAs was observed in 19 (59%) of 32 patients who were eligible for the analyses.
      The curved/straight lengths of the LSAs in the patients with LSA occlusion (23.1
      31.1/17.8-24.3 mm) were significantly shorter than in those without apparent LSA
      occlusion (25.8-39.5/24.0-30.4 mm) ( P = 0.027/0.003). The
      anteroposterior/superoinferior diameters of the infarcts were significantly
      larger in the occluded-LSA group (14.5-21.4/14.9-22.2 mm) than in the intact-LSA
      group (10.9-16.8/10.8-16.2 mm) ( P = 0.041/0.011). In addition, the curved
      lengths of the relevant LSAs showed significant correlations with the
      superoinferior diameters of the infarcts ( r = 0.38, P = 0.034). Conclusion
      Occlusive changes in the LSAs were frequently found in patients with acute
      ischemic stroke within the LSA territory when using HR-MRA at 7 T and were
      substantially related to superoinferior extension of the infarcts.

PMID- 30299230
TI  - Statistical analysis plan for evaluating different intensities of blood pressure
      control in the ENhanced Control of Hypertension And Thrombolysis strokE stuDy.
AB  - BACKGROUND: The ENhanced Control of Hypertension And Thrombolysis strokE study
      (ENCHANTED) trial was initiated as a 2 * 2 partial-factorial active-comparison,
      prospective, randomized, open, blinded endpoint clinical trial to evaluate in
      thrombolysis-eligible acute ischemic stroke (AIS) patients whether: (1) Arm A -
      low-dose (0.6 mg/kg body weight) intravenous (iv) alteplase has noninferior
      efficacy and lower risk of symptomatic intracerebral hemorrhage (sICH) compared
      with standard-dose (0.9 mg/kg body weight) iv alteplase; and (2) Arm B - early
      intensive blood pressure (BP) lowering (systolic target 130-140 mmHg) has
      superior efficacy and lower risk of ICH compared with guideline-recommended BP
      control (systolic target <180 mmHg). Arm A was completed in 2016; Arm B is now
      concluding. OBJECTIVE: To outline in detail and make public the predetermined
      statistical analysis plan (SAP) for the 'BP control' arm of this study. METHODS:
      All data collected by participating researchers will be reviewed and formally
      assessed. Information pertaining to the baseline characteristics of patients,
      their process of care, and the delivery of treatments will be outlined, and for
      each item, statistically relevant descriptive elements will be described. For the
      trial outcomes, the most appropriate statistical comparisons to be made between
      groups are planned and described. RESULTS: A SAP was developed for the results of
      the BP control arm of this study that is transparent, available to the public,
      verifiable, and predetermined before completion of data collection. CONCLUSIONS:
      We have developed a predetermined SAP for the ENCHANTED BP control arm to be
      followed to avoid analysis bias arising from prior knowledge of the study
      findings. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01422616); ISRCTN
      Register (ISRCTN82387104); Australian New Zealand Clinical Trial Registry
      (ACTRN12611000236998); EU Clinical Trials Register (2011-005545-12); and Clinical
      Trials Registry - India (REF/2017/05/014334).

PMID- 30299229
TI  - High five-year mortality rates of ischemic stroke subtypes: A prospective cohort
      study in Brazil.
AB  - BACKGROUND: Studies regarding long-term outcomes of ischemic stroke subtypes are
      scarce in low- and middle-income countries. We aimed to measure the five-year
      prognosis of ischemic stroke subtypes in Joinville, Brazil. METHODS: All first
      ever ischemic strokes that occurred in Joinville in 2010 were followed-up for
      five years. RESULTS: We included 334 ischemic stroke patients. Over five years,
      156 died, 51 had a recurrent stroke, and 128 were free of recurrent stroke. The
      overall cumulative risk of death was 17% (95% CI, 13% to 22%) at 30 days and 47%
      (95% CI, 41% to 52%) after five years. Undetermined with incomplete investigation
      ischemic stroke had a significantly worse survival probability (beta -4.91; 95%
      CI, -6.31 to -3.50; p < 0.001), followed by cardioembolic ischemic stroke (beta 
      3.07; 95% CI, -4.32 to -1.83; p < 0.001) and large artery disease ischemic stroke
      (beta -1.95; 95% CI, -3.30 to -0.60; p = 0.005). The survival probability of
      undetermined with negative investigation or cryptogenic ischemic stroke did not
      differ significantly from small artery disease ischemic stroke (beta -1.022; 95%
      CI, -3.37 to -1.43; p = 0.414). The five-year mortality for small artery disease
      ischemic stroke was 30% (95% CI, 22% to 39%) and 47% (95% CI, 35% to 60%) for
      large artery ischemic stroke. The risk of stroke recurrence was 2% in the first
      year and 5% in the second year. The proportion of disability among survivors in
      the first month ranged from 8% (95% CI, 3-15) for small artery disease ischemic
      stroke to 40% (95% CI, 30-52) for cardioembolic ischemic stroke patients.
      CONCLUSIONS: Cardioembolic and undetermined with incomplete investigation
      ischemic stroke sub-types have a poor long-term prognosis. An alarming finding
      was that our patients with both small and large artery ischemic stroke had higher
      five-year mortality rates compared with subjects from high-income countries.

PMID- 30299231
TI  - Deep Learning-based Method for Fully Automatic Quantification of Left Ventricle
      Function from Cine MR Images: A Multivendor, Multicenter Study.
AB  - Purpose To develop a deep learning-based method for fully automated
      quantification of left ventricular (LV) function from short-axis cine MR images
      and to evaluate its performance in a multivendor and multicenter setting.
      Materials and Methods This retrospective study included cine MRI data sets
      obtained from three major MRI vendors in four medical centers from 2008 to 2016.
      Three convolutional neural networks (CNNs) with the U-NET architecture were
      trained on data sets of increasing variability: (a) a single-vendor, single
      center, homogeneous cohort of 100 patients (CNN1); (b) a single-vendor,
      multicenter, heterogeneous cohort of 200 patients (CNN2); and (c) a multivendor,
      multicenter, heterogeneous cohort of 400 patients (CNN3). All CNNs were tested on
      an independent multivendor, multicenter data set of 196 patients. CNN performance
      was evaluated with respect to the manual annotations from three experienced
      observers in terms of (a) LV detection accuracy, (b) LV segmentation accuracy,
      and (c) LV functional parameter accuracy. Automatic and manual results were
      compared with the paired Wilcoxon test, Pearson correlation, and Bland-Altman
      analysis. Results CNN3 achieved the highest performance on the independent
      testing data set. The average perpendicular distance compared with manual
      analysis was 1.1 mm +/- 0.3 for CNN3, compared with 1.5 mm +/- 1.0 for CNN1 (P <
      .05) and 1.3 mm +/- 0.6 for CNN2 (P < .05). The LV function parameters derived
      from CNN3 showed a high correlation (r2 >= 0.98) and agreement with those
      obtained by experts for data sets from different vendors and centers. Conclusion
      A deep learning-based method trained on a data set with high variability can
      achieve fully automated and accurate cine MRI analysis on multivendor,
      multicenter cine MRI data. (c) RSNA, 2018.

PMID- 30299232
TI  - Clinical Tracking of Cell Transfer and Cell Transplantation: Trials and
      Tribulations.
AB  - Cell therapy has provided unprecedented opportunities for tissue repair and
      cancer therapy. Imaging tools for in vivo tracking of therapeutic cells have
      entered the clinic to evaluate therapeutic cell delivery and retention in
      patients. Thus far, clinical cell tracking studies have been a mere proof of
      principle of the feasibility of cell detection. This review centers around the
      main clinical queries associated with cell therapy: Have cells been delivered
      correctly at the targeted site of injection? Are cells still alive, and, if so,
      how many? Are cells being rejected by the host, and, if so, how severe is the
      immune response? For stem cell therapeutics, have cells differentiated into
      downstream cell lineages? Is there cell proliferation including tumor formation?
      At present, clinical cell tracking trials have only provided information on
      immediate cell delivery and short-term cell retention. The next big question is
      if these cell tracking tools can improve the clinical management of the patients
      and, if so, by how much, for how many, and for whom; in addition, it must be
      determined whether tracking therapeutic cells in every patient is needed. To
      become clinically relevant, it must now be demonstrated how cell tracking
      techniques can inform patient treatment and affect clinical outcomes.

PMID- 30299233
TI  - A Predictive Model for Postembolization Syndrome after Transarterial Hepatic
      Chemoembolization of Hepatocellular Carcinoma.
AB  - Purpose To develop and validate a predictive model for postembolization syndrome
      (PES) following transarterial hepatic chemoembolization (TACE) for hepatocellular
      carcinoma. Materials and Methods In this single-center, retrospective study, 370
      patients underwent 513 TACE procedures between October 2014 and September 2016.
      Seventy percent of the patients were randomly assigned to a training data set and
      the remaining 30% were assigned to a testing data set. Variables included
      demographic, laboratory, clinical, and procedural details. PES was defined as
      pain and/or nausea beyond 6 hours after TACE that required intravenous medication
      for symptom control. The predictive model was developed by using conditional
      inference trees and Lasso regression. Results Demographics, laboratory data,
      performance, tumor characteristics, and procedural details were statistically
      similar for the training and testing data sets. Overall, 83 of 370 patients
      (22.4%) after 107 of 513 TACE procedures (20.8%) met the predefined criteria.
      Factors identified at univariable analysis included large tumor burden (P =
      .004), drug-eluting embolic TACE (P = .03), doxorubicin dose (P = .003), history
      of PES (P < .001) and chronic pain (P < .001), of which history of PES, tumor
      burden, and drug-eluting embolic TACE were identified as the strongest predictors
      by the multivariable analysis and were used to develop the predictive model. When
      applied to the testing data set, the model demonstrated an area under the curve
      of 0.62, sensitivity of 79% (22 of 28), specificity of 44.2% (53 of 120), and a
      negative predictive value of 90% (53 of 59). Conclusion The model identified
      history of postembolization syndrome, tumor burden, and drug-eluting embolic
      chemoembolization as predictors of protracted recovery because of
      postembolization syndrome. (c) RSNA, 2018.

PMID- 30299234
TI  - Carotid Artery Wall Thickness and Incident Cardiovascular Events: A Comparison
      between US and MRI in the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - Purpose To compare common carotid artery (CCA) wall thickness measured manually
      by using US and semiautomatically by using MRI, and to examine their associations
      with incident coronary heart disease and stroke. Materials and Methods This
      prospective study enrolled 698 participants without a history of clinical
      cardiovascular disease (CVD) from the Multi-Ethnic Study of Atherosclerosis
      (MESA) from July 2000 to December 2013 (mean age, 63 years; range, 45 to 84
      years; same for men and women). All participants provided written informed
      consent. CCA wall thickness was measured with US as well as both noncontrast
      proton-density-weighted and intravenous gadolinium-enhanced MRI. Cox proportional
      hazards models were used to assess the associations between wall thickness
      measurements by using US and MRI with CVD outcomes. Results The adjusted hazard
      ratios for coronary heart disease, stroke, and CVD associated with per standard
      deviation increase in intima-media thickness were 1.10, 1.08, and 1.14,
      respectively. The corresponding associations for mean wall thickness measured
      with proton-density-weighted MRI were 1.32, 1.48, and 1.37, and for mean wall
      thickness measured with gadolinium-enhanced MRI were 1.27, 1.58, and 1.38. When
      included simultaneously in the same model, MRI wall thickness, but not intima
      media thickness, remained associated with outcomes. Conclusion For individuals
      without known cardiovascular disease at baseline, wall thickness measurements by
      using MRI were more consistently associated with incident cardiovascular disease,
      particularly stroke, than were intima-media thickness by using US. (c) RSNA, 2018
      Online supplemental material is available for this article.

PMID- 30299235
TI  - Deep Learning for Cardiac MRI: The Time Has Come.

PMID- 30299236
TI  - Alexander R. Margulis, MD.

PMID- 30299237
TI  - Cumulative Radiation Exposures from CT Screening and Surveillance Strategies for
      von Hippel-Lindau-associated Solid Pancreatic Tumors.
AB  - Purpose To assess the potential ionizing radiation exposure from CT scans for
      both screening and surveillance of patients with von Hippel-Lindau (VHL)
      syndrome. Materials and Methods For this retrospective study, abdomen-pelvic (AP)
      and chest-abdomen-pelvic (CAP) CT scans were performed with either a three-phase
      (n = 1242) or a dual-energy virtual noncontrast protocol (VNC; n = 149) in 747
      patients with VHL syndrome in the National Institutes of Health Clinical Center
      between 2009 and 2015 (mean age, 47.6 years +/- 14.6 [standard deviation]; age
      range, 12-83 years; 320 women [42.8%]). CT scanning parameters for patients with
      pancreatic neuroendocrine tumors (PNETs; 124 patients and 381 scans) were
      compared between a tumor diameter-based surveillance protocol and a VHL genotype
      and tumor diameter-based algorithm (a tailored algorithm) developed by three VHL
      clinicians. Organ and lifetime radiation doses were estimated by two radiologists
      and five radiation scientists. Cumulative radiation doses were compared between
      the PNET surveillance algorithms by analyses of variance, and a two-tailed P
      value less than .05 indicated statistical significance. Results Median cumulative
      colon doses for annual CAP and AP CT scans from age 15 to 40 years ranged from
      0.34 Gy (5th-95th percentiles, 0.18-0.75; dual-energy VNC CT) to 0.89 Gy (5th
      95th percentiles, 0.42-1.0; three-phase CT). For the current PNET surveillance
      protocol, the cumulative effective radiation dose from age 40 to 65 years was 682
      mSv (tumors < 1.2 cm) and 2125 mSv (tumors > 3 cm). The tailored algorithm could
      halve these doses for patients with initial tumor diameter less than 1.2 cm (P <
      .001). Conclusion CT screening of patients with von Hippel-Lindau syndrome can
      lead to substantial radiation exposures, even with dual-energy virtual
      noncontrast CT. A genome and tumor diameter-based algorithm for pancreatic
      neuroendocrine tumor surveillance may potentially reduce lifetime radiation
      exposure. (c) RSNA, 2018 Online supplemental material is available for this
      article.

PMID- 30299239
TI  - Successful use of rituximab in granulomatosis with polyangiitis with aortic
      inflammation.
AB  - Large vessel inflammation, although rare, has been increasingly recognised as a
      complication of granulomatosis with polyangiitis (GPA) in recent years. The
      presentation is highly variable, ranging from an incidental finding to aortic
      dissection and rupture. Treatment has predominately consisted of a combination of
      cyclophosphamide and high dose corticosteroids with surgical intervention when
      indicated. We present the case of a 34-year-old male diagnosed with GPA after
      presenting with sinus and eye inflammation and the ensuing investigation revealed
      large vessel involvement that remarkably improved after 6 months of treatment
      with the combination of rituximab infusions, methotrexate and corticosteroids.

PMID- 30299238
TI  - Human papilloma virus genotype distribution and risk factor analysis amongst
      reproductive-age women in urban Gambia.
AB  - PURPOSE: Cervical cancer is the most frequently diagnosed female cancer in The
      Gambia, representing approximately 30 % of cases. In 2014, the quadrivalent human
      papilloma virus (HPV) vaccine was introduced, which offers protection against HPV
      genotypes 6, 11, 16 and 18. To evaluate the potential effectiveness of this
      vaccine, genotype distribution and risk factor analysis were assessed.
      METHODOLOGY: Endocervical samples (n=232) were collected from women aged 20-49
      years residing in urban Gambia. A questionnaire was administered to capture socio
      demographic and cervical cancer risk factors. HPV detection and genotyping was
      performed by PCR amplification of the L1 major capsid gene and analysis of
      sequenced PCR products.Results/Key findings. The prevalence of HPV was 12 %
      (28/232), and the high-risk (HR) genotype HPV 52 (5/28) was the most prevalent
      genotype. HR-HPV sequences had high identity (>=90 %) to isolates which
      originated from America, Europe and Asia but not from Africa. Half (14/28) of
      participants were co-infected with Ureaplasma urealyticum/parvum, which increases
      the risk of progression to cervical cancer. Female genital mutilation and the use
      of hormone contraception for >5 years were identified as potential risk factors
      for HPV infection. Ethnicity-associated differences were also noted; participants
      of the Fula ethnic group had a higher prevalence of HR-HPV infection (31.3 %)
      compared to the Mandinka (18.8 %) and Wollof (12.5 %) groups. CONCLUSION: These
      data may have a significant public health impact as the HPV quadrivalent vaccine
      may be of limited value if the circulating non-HPV 16/18 HR-genotypes are
      responsible for cytological abnormalities of the cervix.

PMID- 30299240
TI  - Antinuclear antibodies in the general population: positive association with
      inflammatory and vascular biomarkers but not traditional cardiovascular risk
      factors.
AB  - OBJECTIVES: Patients with clinically evident autoimmune disease are at increased
      risk for premature cardiovascular disease (CVD). Markers of serological
      autoimmunity such as anti-nuclear antibodies (ANA) are found in approximately 25%
      of the general population. Yet, the vast majority will not develop clinical
      autoimmune disease. Serological autoimmunity is a risk factor for CVD death in
      individuals without autoimmune disease; however, the mechanisms mediating this
      excess CVD risk have not been elucidated. METHODS: We examined associations of
      ANA with traditional cardiovascular risk factors, inflammatory mediators, and
      vascular biomarkers in the Dallas Heart Study - a large, representative
      multiethnic population-based cohort. Plasma ANA were measured by enzyme linked
      immunosorbent assay in 3,488 Dallas Heart Study participants aged 30 to 65 years
      who do not have known rheumatologic disease. Associations of ANA with demographic
      characteristics, cardiovascular risk factors, and biomarkers were assessed using
      univariable and multivariable linear regression. RESULTS: Factors independently
      associated with higher ANA include female sex, African-American race/ethnicity,
      soluble intracellular adhesion molecule-1, soluble CD40 ligand, chemokine CXCL-2,
      and Cystatin C (p<0.05 for each). ANA was not associated with traditional
      cardiovascular risk factors, high sensitivity C-reactive protein, coronary artery
      calcium scores, or aortic wall thickness. CONCLUSION: ANA are associated with
      inflammatory mediators and biomarkers of vascular activation, but not with
      traditional cardiovascular risk factors in a multiethnic population-based cohort.
      These findings suggest that the cardiovascular risk associated with ANA may
      involve pathways distinct from traditional risk factors and include dysregulation
      of endothelial cells and the immune system.

PMID- 30299241
TI  - Efficacy of tocilizumab monotherapy after response to combined tocilizumab and
      methotrexate in patients with rheumatoid arthritis: the randomised JUST-ACT
      study.
AB  - OBJECTIVES: The aim of the JUST-ACT study was to assess whether the add-on effect
      of tocilizumab (TCZ) to background methotrexate (MTX) observed in MTX-inadequate
      responders with active rheumatoid arthritis (RA), would be sustained when MTX is
      withdrawn. METHODS: A double-blind, parallel-group, phase 3 study in biologic
      naive RA patients with a disease activity score 28 (DAS28)>3.2 despite MTX which
      were treated with TCZ+MTX for an initial 16-week period. Patients who at week 16
      achieved low disease activity (LDA) (DAS28<=3.2) were randomised to continue with
      TCZ+MTX or switch to TCZ + placebo (PBO) for an additional 12 weeks. The primary
      endpoint was the change in DAS28-ESR from the randomisation at week 16 to week
      28. Non-inferiority was confirmed if the upper limit of the two-sided 95%CI for
      the treatment difference between TCZ+MTX and TCZ monotherapy groups was lower
      than the selected non-inferiority margin of 0.6. RESULTS: 261 patients completed
      the first 16 weeks of TCZ+MTX treatment and 165 were randomised (83 to TCZ+MTX
      and 82 to TCZ+PBO). For the primary endpoint, the adjusted treatment difference
      (95% CI) in mean change of DAS28-ESR was -0.06 (-0.40 to 0.27), and therefore the
      non-inferiority of switching to TCZ monotherapy versus continuing with TCZ+MTX
      was demonstrated. In both treatment groups, the percentage of patients in
      clinical remission from 16 to 28 weeks was similar as were the improvements in
      disease activity, functional disability and quality of life. CONCLUSIONS: In MTX
      non-responder patients achieving LDA with TCZ+MTX, switching to TCZ monotherapy
      is non-inferior to continuing the combination.

PMID- 30299242
TI  - Inflammation and cardiovascular disease in familial Mediterranean fever. An
      analysis of hospital admissions for acute cardiovascular event.
AB  - OBJECTIVES: Patients, suffering from inflammatory disorders, are at an increased
      risk to develop cardiovascular disease (CVD). Here, we examine whether in
      familial Mediterranean fever (FMF), a model of inflammatory diseases,
      inflammation also increases the risk to develop cardiovascular (CV) disease.
      METHODS: To explore the role of inflammation in the occurrence of CVD in FMF, we
      identified all FMF patients <=55 years old with CVD, admitted to our center over
      a 15-year period. Correlates of inflammation, such as severity of FMF and dose of
      colchicine, as well as the presence of traditional CV risk factors were compared
      between the FMF patients with CVD (FMF- CVD) and control FMF patients with- out
      CVD. RESULTS: Twenty-three FMF-CVD and 40 control patients were compared. The
      severity of FMF, and the dose of colchicine, were similar in the 2 study groups;
      therefore, not associated with CVD. Compared with FMF patients without CVD, the
      FMF-CVD group comprised a higher proportion of men (78 vs. 40% p=0.005), and of
      patients with diabetes (31 vs. 7%, p=0.016) and inflammatory comorbidities such
      as Behcet's disease (30 vs. 7%, p=0.005). Multivariate analysis revealed that
      only diabetes mellitus and inflammatory comorbidities were independent factors
      associated with FMF-CVD. CONCLUSIONS: In FMF patients treated with colchicine,
      CVD is not associated with FMF-related inflammation.

PMID- 30299243
TI  - Why are Behcet's disease patients always exhausted?
AB  - OBJECTIVES: Patients with Behcet's disease (BD) constantly complain of fatigue
      and many have problems with poor sleep. This ultimately has a major impact on all
      aspects of normal living. To attempt to understand this, Artificial Intelligence
      (AI) was used to identify potential biomarkers. These were alpha-melanocyte
      stimulating hormone (alpha-MSH), vasoactive intestinal peptide (VIP) and some
      inflammatory cytokines. We assessed the association of fatigue, quality of sleep
      and disease activity with circulating concentration of alpha-MSH, VIP and
      inflammatory cytokines. METHODS: There were 127 participants, 97 BD patients, and
      30 healthy controls (HC). All completed the Multi-Dimensional Assessment of
      Fatigue questionnaire (MAF) and the Pittsburgh Sleep Quality Index (PSQI) on the
      day of their clinical assessment. Enzyme-linked immunosorbent assays (ELISA) were
      used to evaluate the serum concentrations of alpha-MSH, VIP and cytokines (IL
      1beta, IL-6, IL-10, and TNF-alpha). RESULTS: 64% of BD patients experienced high
      fatigue scores, and 63% had poor quality of sleep. When BD and HC were compared
      the MAF and PSQI scores as well as the serum concentrations of alpha-MSH, VIP,
      and IL-6 were significantly higher in BD (p values were: 0.001, 0.001, 0.001,
      0.004 and 0.036, respectively). Both alpha-MSH and IL-6 had significant impact on
      MAF and PSQI. Interestingly, VIP had a significant influence on PSQI and disease
      activity, but not on MAF. CONCLUSIONS: A better understanding of these complex
      clinical and biochemical interactions between alpha-MSH, VIP and IL-6 might lead
      to the development of novel approaches to manage fatigue and sleep disorders as
      well as disease activity in BD patients.

PMID- 30299244
TI  - Short-term clinical worsening is a clear predictor for worsening at 2 years in
      established knee and hip osteoarthritis.
AB  - OBJECTIVES: Our aim was to estimate the proportion of knee and hip OA patients
      showing worsening at 2 years, and to examine the additional predictive value of
      failure of optimised non-surgical treatment during 3 months for worsening at 2
      years. METHODS: Data of patients participating in the longitudinal CONTROL-PRO
      study (patients fulfilling clinical ACR criteria for knee or hip OA) were used.
      Measurements of pain, functioning and patient global assessments were performed
      at baseline, 3 months and 2 years. Worsening at 2 years was defined as fulfilling
      the recently validated clinical worsening criteria for knee and hip OA, or total
      joint replacement (TJR). Logistic regression was performed with worsening at 2
      years as the dependent variable. RESULTS: The 297 included patients were
      predominantly women (66%) with a mean age of 55 years. At 2 years, 61% showed
      worsening (knee 59%; hip 71%) and 24% had undergone a TJR (knee 19%; hip 51%).
      Clinical worsening at 3 months appeared to be a clear independent predictor for
      worsening at 2 years (OR 2.8 95% CI 1.5-5.2) with a moderate discriminative
      ability (AUC 0.68 95% CI 0.57-0.70). Similar results were obtained when only TJR
      at 2 years was used as the outcome measure (OR 4.1 95% CI 2.0-8.4) with good AUC
      (0.82 95% CI 0.76-0.87). CONCLUSIONS: Our findings suggest that re-assessment of
      symptoms after optimised non-surgical treatment could be meaningful in clinical
      decision making for TJR. Furthermore, this information could be used to identify
      subgroups of patients potentially eligible for novel and advanced treatment
      options.

PMID- 30299245
TI  - Epidemiological characteristics of psoriatic arthritis.
AB  - Psoriatic arthritis (PsA) is a specific form of inflammatory arthritis associated
      with skin psoriasis. PsA makes part of a heterogeneous group of arthritides
      called the spondyloarthropathies. Several studies regarding the prevalence and
      incidence of PsA have been published during the last decades, showing a
      considerable variation of the disease occurrence among different populations. The
      purpose of this review is to discuss recent observations of epidemiological
      features for PsA patients. Thus, the literature was reviewed until May 2018 for
      studies regarding PsA epidemiology, classification criteria and risk factors for
      PsA development. Systematic reviews based on the international bibliography, are
      reporting the prevalence of the disease from 1/100.000 inhabitants in Japan to as
      high as 420/100.000 inhabitants in Italy. The annual incidence also varies,
      ranging from 1 to 23/100.000 inhabitants, while the average incidence rate is 6.5
      cases/100.000 inhabitants. The random effect pooled PsA prevalence and incidence
      rates are 133/100.000 and 83/100.000 subjects respectively. Thus, a large
      heterogeneity between studies is observed. This variability could be explained by
      a number of factors such as the use of multiple and different classification
      criteria in the studies. Geographical variations are also observed regarding
      disease occurrence. Differences were found not only between different continents,
      but also within the same geographic regions. This could be explained by the
      different genetic background especially the distribution of the human leucocyte
      antigens. In addition, other factors such as environmental (infections, climate,
      sun exposure), dietary habits (fish oil consumption, Mediterranean diet) or life
      style habits (obesity, smoking), could explain the geographic variability in the
      prevalence estimates. The implementation of unanimous classification criteria and
      the conformation by the scientific community could lead to a better understanding
      of the disease epidemiology.

PMID- 30299246
TI  - Implication of CXCL5 (epithelial neutrophil-activating peptide 78) in the
      development of insulin resistance in patients with rheumatoid arthritis.
AB  - OBJECTIVES: The chemokine molecule CXCL5 (C-X-C motif chemokine ligand 5, also
      known as epithelial neutrophil activating peptide 78 -ENA78-) constitutes a link
      between obesity, inflammation and insulin resistance (IR) in the general
      population. CXCL5 has also been found to play a role in rheumatoid arthritis (RA)
      pathogenesis. Since chronic inflammation promotes IR and impairs pancreatic beta
      cell function in RA patients, we assessed the role of CXCL5 in the development of
      IR in RA. METHODS: Cross-sectional study that encompassed 141 non-diabetic
      patients with RA. IR assessed by homeostatic model assessment (HOMA2), insulin
      and C-peptide serum levels and lipid profile, and CXCL5 serum levels were
      studied. Regression analysis was performed to evaluate how CXCL5 was related to
      IR, disease activity, and disease characteristics in RA patients. RESULTS: HOMA2
      IR indexes showed high values for both IR and beta cell production (%B), and low
      insulin sensitivity (%S) in patients with RA. C reactive protein (beta coef. 0.2
      [95%CI -1.5-1.9], p=0.80) and disease activity through DAS28 (beta coef. 13
      [95%CI -14-41], p=0.34) revealed no relation with CXCL5. Other disease
      characteristics, such as disease duration, serological status, or use of
      methotrexate or anti-TNF alpha therapies, were not associated with CXCL5 serum
      levels. While glucocorticoids were related to insulin, C-peptide serum levels,
      and HOMA2-IR and HOMA2-%B-C peptide, the use of prednisone was not associated
      with CXCL5 serum levels. Insulin and C peptide serum levels and IR indexes showed
      strong correlations among each other, but not with CXCL5 (insulin r2=-0.034,
      p=0.69; C peptide r2=-0.050, p=0.56). CONCLUSIONS: CXCL5 is not related to IR in
      RA patients. Therefore, the mechanisms leading to IR in patients with RA may be
      different from those in the general population.

PMID- 30299247
TI  - Prevalence of sicca syndrome in the Peruvian population.
AB  - OBJECTIVES: Sjogren's syndrome is a complex and heterogeneous autoimmune disease
      characterised by ocular and oral dryness (1), which mainly affects the exocrine
      glands. The objective of this study was to determine the prevalence of sicca
      syndrome (SS) in the Peruvian population. The age and gender of patients with SS
      and their national prevalence and in each of the departments were defined.
      METHODS: Cross-sectional prevalence study. All the people that the Ministry of
      Health (MINSA) in Peru covered health treatments from January to December 2016
      were taken into account. The patients with SS were newly or previously diagnosed
      with sicca syndrome (Sjogren's) according to the international classification of
      diseases version 10 (ICD-10) of the World Health Organization (WHO). The
      prevalence was determined considering the number of cases of SS in the total
      population registered by the Ministry of Health (MINSA). RESULTS: 1,301 cases of
      SS were observed in a total population of 15,417,345 people served in 25
      territories. The prevalence of SS in this population was 0.0084%, the prevalence
      rate was 8.4 cases per 100,000 persons (95% CI: 7.99-8.91). The prevalence of SS
      was higher in the territories of Tacna, Lima, La Libertad, Arequipa, Callao, and
      Apurimac. CONCLUSIONS: The results of this study show the prevalence of SS in the
      Peruvian population and serve to strengthen the health strategies of
      rheumatology, ophthalmology, and oral health to improve the diagnosis, treatment,
      follow-up of the disease, and the quality of life of patients with SS.

PMID- 30299248
TI  - Serum calprotectin as a marker of clinical and ultrasound-detected synovitis in
      early psoriatic and rheumatoid arthritis: results from a cross-sectional
      retrospective study.
AB  - OBJECTIVES: We aimed to evaluate the correlation between serum calprotectin and
      clinical and ultrasonographic (US) variables in early-onset psoriatic arthritis
      (PsA) and controls with rheumatoid arthritis (RA). METHODS: In a retrospective
      cross-sectional study, including PsA and matched RA patients, 44 joint counts
      (TJC, SJC), calprotectin, ESR and CRP were measured. US of wrists and MCPs 1-5
      was performed, with grey-scale (GS) and power Doppler (PD) scored 0-3 at each
      site, summed in a total score. The correlation between calprotectin, clinical and
      US variables was evaluated by Spearman's coefficient, the predictivity by
      calprotectin of US by regression. Secondary analyses separating polyarticular PsA
      and using different US definitions (GS>1, PD>1) were performed. RESULTS: 78 PsA
      and 78 RA were included (PsA male 32%; mean age 51.7 (13.5)). Calprotectin did
      not significantly differ in PsA and RA. In PsA, calprotectin correlated with GS
      score (rho=0.340, p=0.008), PD score (rho=0.292, p=0.023) and the presence of PD
      (rho=0.263, p=0.042); in RA there were no significant correlations. In
      polyarticular PsA, a significant correlation between calprotectin and GS
      (rho=0.369, p=0.019) and PD scores (rho=0.363, p=0.021) was confirmed. In both
      PsA and RA, calprotectin and CRP significantly correlated, while SJC and TJC did
      not. In the regression analysis, calprotectin did not predict US variables in
      PsA. Similar results were achieved in RA. CONCLUSIONS: In early PsA, serum
      calprotectin correlates with US measures of disease activity. Our results provide
      preliminary evidence for the application of this biomarker in early PsA.

PMID- 30299249
TI  - Does the cognitive index of the symptom severity scale (SSS) evaluate cognition?
      Data from subjective and objective cognitive measures in fibromyalgia.
AB  - OBJECTIVES: The current provisional diagnostic criteria for the fibromyalgia
      syndrome (FM) include a cognitive index score (SSS-Cog), which constitutes a part
      of the Symptom Severity Scale (SSS). The current study aimed at assessing the
      validity of the cognitive index score, by comparing this subjective measure of
      cognitive impairment with an objective measure of cognitive functioning,
      collected through comprehensive computerised cognitive testing and assessment.
      METHODS: 50 FM patients underwent a computerised cognitive assessment battery,
      including testing in domains of memory, executive function, attention and
      information processing speed (NeuroTraxCorp.). Age and education standardised
      scores were computed. FM symptoms were assessed by the Fibromyalgia Impact
      Questionnaire (FIQ), Widespread Pain Index (WPI) and Symptom Severity Scale
      (SSS), a Visual Analog Scale (VAS) of clinical pain and the Beck Depression
      inventory (BDI-II). RESULTS: The index score for subjective assessment of
      cognitive decline (SSS-Cog) was not correlated with any of the objective
      cognitive measures. However, a positive correlation was found between the SSS-Cog
      and the FIQ, the WPI and the VAS measures, all reflecting subjective overall
      functional ability. CONCLUSIONS: No significant relationship was found between FM
      patients' subjective appraisal of cognitive deficit and objective cognitive
      scores on all computerised subtests. However, subjective appraisal of cognitive
      impairment was found to be strongly and significantly related to patients'
      functional ability. Therefore, we suggest reconsidering the definition of this
      index score (SSS-Cog) and propose developing novel and more accurately defined
      tools in order to measure cognitive impairment in FM patients, for both
      diagnostic and epidemiological purposes.

PMID- 30299250
TI  - Increased interleukin-22 levels in lupus nephritis and its associated with
      disease severity: a study in both patients and lupus-like mice model.
AB  - OBJECTIVES: Interleukin-22 (IL-22) has been considered as an inflammatory
      cytokine. In the present study, we investigated the potential role of IL-22 in
      lupus nephritis (LN). METHODS: We examined the IL-22 levels of serum and kidney
      tissue from LN patients and MRL/lpr mice. An intraperitoneal injection of saline,
      isotype control antibody (IgG), prednisone (3mg/kg/mouse), or anti-IL-22 mAb
      (5MUg/kg/mouse or 25MUg/kg/mouse) was administered twice a week from 6 to 18
      weeks of age. RESULTS: IL-22 levels in both serum and kidney were significantly
      higher in LN patients as compared with those in healthy controls. The serum and
      renal levels of IL-22 in MRL/lpr mice were significantly increased over time.
      After MRL/lpr mice were treated with anti-IL-22 monoclonal antibody (mAb) for 12
      weeks, significantly less urine protein and lower serum levels of creatinine and
      urea nitrogen were found. In addition, less renal injury score and few number of
      inflammatory cells per glomerulus were observed in MRL/lpr mice treated with anti
      IL-22 mAb as compared with control groups. CONCLUSIONS: Our results suggest that
      IL-22 as a pathogenic cytokine might be a potential target for treatment of lupus
      nephritis.

PMID- 30299251
TI  - Clinical and genetic characteristics of ankylosing spondylitis patients with
      peripheral arthritis at disease onset.
AB  - OBJECTIVES: The aim of this study was to assess the clinical and genetic
      characteristics associated with the presence of peripheral arthritis (PA) at
      disease onset in patients with ankylosing spondylitis (AS). METHODS: 456 Spanish
      AS patients, diagnosed according to the modified New York Criteria, who had at
      least ten years of follow-up since initial disease onset were selected from the
      National Spondyloarthropathies Registry (REGISPONSER). 18.9% of AS patients
      initially presented PA. Clinical variables and 384 single nucleotide
      polymorphisms (SNPs) distributed in 190 genes were analysed. SNP genotyping was
      performed using the Illumina GoldenGate genotyping platform. Association tests
      for allele frequencies and for categorical clinical variables were performed by
      the chi2 test and with the unpaired t-test for continuous variables. p-values of
      <0.05 were considered statistically significant. RESULTS: AS patients with PA
      showed an earlier age of disease onset (p=0.021), longer disease duration
      (p=0.020) and longer duration of AS symptoms from onset (p=0.034) than AS
      patients without PA. We found significant associations with the presence of PA at
      disease onset in 14 SNPs located in 10 genes: HLA-DQB2 (rs2857210 and rs9276615),
      HLA-DOB (rs2857151, rs2621332 and rs1383261), JAK2 (rs7857730), IL-23R
      (rs11209008 and rs10489630), CYP1B1 (rs1056836), NELL1 (rs8176786), KL
      (rs564481), and MEFV (rs224204), IL-2RB (rs743777) and IL-1A (rs1800587).
      CONCLUSIONS: Both clinical and genetic factors are associated with the presence
      of PA at disease onset in Spanish AS patients. The results suggest that this
      subset of AS patients with PA at disease onset might have differentiation factors
      involved in disease pathogenesis.

PMID- 30299252
TI  - Association of a polymorphism of the Fcgamma-receptor 2A (FCGR2A) gene with
      chronic periaortitis.
AB  - OBJECTIVES: Chronic periaortitis (CP) is an inflammatory disease associated in 20
      60% of the cases with IgG4 related disease. Current evidence supports an
      autoimmune nature for CP. Fc gamma receptors (FcgammaRs) are involved in several
      immune system activities and are associated with autoimmunity in general. We
      explored the influence of genetic variants within this region on susceptibility
      to CP. METHODS: Genotyping of 4 candidate single nucleotide polymorphisms (SNPs)
      of the FCGR region was performed in CP patients and controls. RESULTS: One
      hundred and eighty-three cases and 181 controls were included. An association
      between the SNP rs1801274 of the FCGR2A and CP was detected (OR 1.6, 95%CI 1.18
      2.16;corrected p-value, pcorr=0.0085). After stratification of the population
      according to clinical characteristics, the association was restricted to cases of
      idiopathic retroperitoneal fibrosis (OR 1.66, 95%CI 1.21-2.29;pcorr=0.028),
      without involvement of the thoracic aorta (OR 1.77, 95%CI 1.21-2.57;pcorr=0.043),
      with deep vein thrombosis at onset (OR 3.96, 95%CI 1.81-8.66;pcorr=0.0021) and
      with normal IgG4 levels (OR 2.67, 95%CI 1.39-5.12;pcorr=0.031). CONCLUSIONS: In
      the largest candidate gene approach study performed so far in CP, we demonstrated
      an association for CP with a gene hallmark of autoimmunity. The association
      appears restricted to typical cases of CP without increase of IgG4 levels.

PMID- 30299253
TI  - Mitochondria reorganization upon proliferation arrest predicts individual yeast
      cell fate.
AB  - Most cells spend the majority of their life in a non-proliferating state. When
      proliferation cessation is irreversible, cells are senescent. By contrast, if the
      arrest is only temporary, cells are defined as quiescent. These cellular states
      are hardly distinguishable without triggering proliferation resumption, hampering
      thus the study of quiescent cells properties. Here we show that quiescent and
      senescent yeast cells are recognizable based on their mitochondrial network
      morphology. Indeed, while quiescent yeast cells display numerous small vesicular
      mitochondria, senescent cells exhibit few globular mitochondria. This allowed us
      to reconsider at the individual-cell level, properties previously attributed to
      quiescent cells using population-based approaches. We demonstrate that cell's
      propensity to enter quiescence is not influenced by replicative age, volume or
      density. Overall, our findings reveal that quiescent cells are not all identical
      but that their ability to survive is significantly improved when they exhibit the
      specific reorganization of several cellular machineries.

PMID- 30299254
TI  - Range, routing and kinetics of rod signaling in primate retina.
AB  - Stimulus- or context-dependent routing of neural signals through parallel
      pathways can permit flexible processing of diverse inputs. For example, work in
      mouse shows that rod photoreceptor signals are routed through several retinal
      pathways, each specialized for different light levels. This light-level-dependent
      routing of rod signals has been invoked to explain several human perceptual
      results, but it has not been tested in primate retina. Here, we show,
      surprisingly, that rod signals traverse the primate retina almost exclusively
      through a single pathway - the dedicated rod bipolar pathway. Identical
      experiments in mouse and primate reveal substantial differences in how rod
      signals traverse the retina. These results require reevaluating human perceptual
      results in terms of flexible computation within this single pathway. This
      includes a prominent speeding of rod signals with light level - which we show is
      inherited directly from the rod photoreceptors themselves rather than from
      different pathways with distinct kinetics.

PMID- 30299255
TI  - The DWORF micropeptide enhances contractility and prevents heart failure in a
      mouse model of dilated cardiomyopathy.
AB  - Calcium (Ca2+) dysregulation is a hallmark of heart failure and is characterized
      by impaired Ca2+ sequestration into the sarcoplasmic reticulum (SR) by the SR
      Ca2+-ATPase (SERCA). We recently discovered a micropeptide named DWORF (DWarf
      Open Reading Frame) that enhances SERCA activity by displacing phospholamban
      (PLN), a potent SERCA inhibitor. Here we show that DWORF has a higher apparent
      binding affinity for SERCA than PLN and that DWORF overexpression mitigates the
      contractile dysfunction associated with PLN overexpression, substantiating its
      role as a potent activator of SERCA. Additionally, using a well-characterized
      mouse model of dilated cardiomyopathy (DCM) due to genetic deletion of the muscle
      specific LIM domain protein (MLP), we show that DWORF overexpression restores
      cardiac function and prevents the pathological remodeling and Ca2+ dysregulation
      classically exhibited by MLP knockout mice. Our results establish DWORF as a
      potent activator of SERCA within the heart and as an attractive candidate for a
      heart failure therapeutic.

PMID- 30299257
TI  - Smoking-induced changes in leptin serum levels and c/EBPalpha-related methylation
      status of the leptin core promotor during smoking cessation.
AB  - Previous studies have provided evidence of an association between serum leptin
      levels and smoking as well as craving during smoking cessation. As promoter
      methylation also regulates leptin expression, we investigated the leptin gene
      promoter region of smokers before and after smoking cessation. Since leptin's
      core promoter region contains an essential c/EBPalpha transcription binding site,
      we narrowed our investigation to C-300 (-300 base pairs from the transcription
      start site) of that binding site. Female smokers showed hypermethylation of C-300
      compared to non-smokers. Global methylation status is associated with higher
      craving and the degree of dependence in female smokers. Serum leptin levels in
      female smokers were significantly higher than in non-smokers. These findings
      support previous results and, for the first time, point to a pathophysiological
      role of c/EBPalpha-related C-300 methylation in tobacco dependence.

PMID- 30299258
TI  - Raloxifene as a treatment for cognition in women with schizophrenia: the
      influence of menopause status.
AB  - Cognitive impairments cause significant functional issues for people with
      schizophrenia, often emerging before the onset of hallucinations, delusions and
      other psychosis symptoms. Current pharmacological treatments do not target
      cognitive dysfunction. Several lines of evidence support the beneficial effects
      of estrogens on cognition. Raloxifene hydrochloride, a selective estrogen
      receptor modulator, has been associated with cognitive improvements in healthy
      postmenopausal women and in schizophrenia, although findings are inconsistent.
      Using pooled data from two clinical trials, the aim of the current study was to
      compare the efficacy of 120 mg/day adjunctive raloxifene to placebo for 12 weeks
      on cognitive performance in women with schizophrenia who were stratified by
      menopause status (pre-menopausal; peri-menopausal or post-menopausal). A total of
      sixty-nine participants with a diagnosis of schizophrenia or schizoaffective
      disorder were included. Cognition was assessed at baseline and study end using
      the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
      Results indicated that after stratifying for menopause status (strata) and
      adjusting for endogenous hormone levels (estrogen, progesterone, follicle
      stimulating hormone and luteinising hormone), semantic fluency, picture naming
      and list recognition change from baseline scores for the raloxifene group
      differed significantly from the placebo group. The findings from the current
      study highlight the importance of considering menopause status when interpreting
      the effects of hormonal treatments.

PMID- 30299256
TI  - Transition between fermentation and respiration determines history-dependent
      behavior in fluctuating carbon sources.
AB  - Cells constantly adapt to environmental fluctuations. These physiological changes
      require time and therefore cause a lag phase during which the cells do not
      function optimally. Interestingly, past exposure to an environmental condition
      can shorten the time needed to adapt when the condition re-occurs, even in
      daughter cells that never directly encountered the initial condition. Here, we
      use the molecular toolbox of Saccharomyces cerevisiae to systematically unravel
      the molecular mechanism underlying such history-dependent behavior in transitions
      between glucose and maltose. In contrast to previous hypotheses, the behavior
      does not depend on persistence of proteins involved in metabolism of a specific
      sugar. Instead, presence of glucose induces a gradual decline in the cells'
      ability to activate respiration, which is needed to metabolize alternative carbon
      sources. These results reveal how trans-generational transitions in central
      carbon metabolism generate history-dependent behavior in yeast, and provide a
      mechanistic framework for similar phenomena in other cell types.

PMID- 30299259
TI  - Falling in love is associated with immune system gene regulation.
AB  - Although falling in love is one of the most important and psychologically potent
      events in human life, the somatic implications of new romantic love remain poorly
      understood. Psychological, immunological, and reproductive perspectives offer
      competing predictions of the specific transcriptional regulatory shifts that
      might accompany the experience of falling in love. To characterize the impact of
      romantic love on human genome function, we conducted genome-wide transcriptome
      profiling of 115 circulating immune cell samples collected from 47 young women
      over the course of a 2-year longitudinal study. Analyses revealed a selective
      alteration in immune cell gene regulation characterized by up-regulation of Type
      I interferon response genes associated with CD1C+/BDCA-1+ dendritic cells (DCs)
      and CLEC4C+/BDCA-2+ DCs, and a reciprocal down-regulation of alpha-defensin
      related transcripts associated with neutrophil granulocytes. These effects
      emerged above and beyond the effects of changes in illness, perceived social
      isolation, and sexual contact. These findings are consistent with a selective up
      regulation of innate immune responses to viral infections (e.g., Type I
      interferons and DC) and with DC facilitation of sexual reproduction, and provide
      insight into the immunoregulatory correlates of one of the keystone experiences
      in human life.

PMID- 30299260
TI  - Ciliary neurotrophic factor is a key sex-specific regulator of depressive-like
      behavior in mice.
AB  - Ciliary neurotrophic factor (CNTF) is produced by astrocytes and promotes
      neurogenesis and neuroprotection. Little is known about the role of CNTF in
      affective behavior. We investigated whether CNTF affects depressive- and anxiety
      like behavior in adult mice as tested in the forced swim, sucrose preference and
      elevated-T maze tests. Female wild type CNTF+/+ mice more readily developed
      behavioral despair with increased immobility time and decreased latency to
      immobility in the forced swim test than male CNTF+/+ littermates. The lack of
      CNTF in CNTF-/- mice had an opposite effect on depressive-like behavior in female
      mice (reduced immobility time and increased sucrose preference) vs. male mice
      (increased immobility time). Female wildtype mice expressed more CNTF in the
      amygdala than male mice. Ovariectomy increased CNTF expression, as well as
      immobility time, which was significantly reduced in CNTF-/- mice, suggesting that
      CNTF mediates overiectomy-induced immobility time, possibly in the amygdala.
      Progesterone but not 17-beta estradiol inhibited CNTF expression in cultured C6
      astroglioma cells. Progesterone treatment also reduced CNTF expression in the
      amygdala and decreased immobility time in female CNTF+/+ but not in CNTF-/- mice.
      Castration did not alter CNTF expression in males nor their behavior. Lastly,
      there were no effects of CNTF on the elevated T-maze, a behavioral test of
      anxiety, suggesting that a different mechanism may underlie anxiety-like
      behavior. This study reveals a novel CNTF-mediated mechanism in stress-induced
      depressive-like behavior and points to opportunities for sex-specific treatments
      for depression, e.g. progesterone in females and CNTF-stimulating drugs in males.

PMID- 30299261
TI  - Effectiveness of Percutaneous Intradiscal Decompression Therapy in Thoracic Disc
      Herniation.
AB  - AIMS: Although there have been many studies about lomber and cervical ablation
      procedures, very few studies have been performed on the thoracic region. This is
      a study to evaluate the clinical results of percutaneous disc decompression
      device in patients with radicular symptoms and/or dorsal pain due to thoracic
      disc herniation. METHODS: Eleven patients with thoracic disc herniation and/or
      degenerative discs (all in T10-T11, or T11-T12 levels) who did not respond to
      conservative treatments were undergo ablation and compression procedure. Pain and
      radicular symptoms consistent with the thoracolumbar region were confirmed via
      abnormal magnetic resonans image findings after detailed anamnesis and physical
      examination. All patients were evaluated before and 1, 3, 6 and 12 months after
      treatment using the visual analoge scale score. The Patient Satisfaction Scale
      was used to evaluate the level of patient satisfaction at the end of the
      treatment at 12 months. RESULTS: Median visual analoge scale score was 7.00+/
      0.45 points before treatment, and 2.73+/-0.65 points at 12 month post-procedure
      were statistically significant (p<0.001). The results of pairwise comparisons
      using the Bonferroni Corrected Wilcoxon Signed-Rank test showed that there were
      statistically significant differences. The mean visual analoge scale score at the
      beginning (7.00+/-0.45) was significantly higher than the mean score at the other
      months Postoperative improvement was significant with a 99% confidence interval.
      No complications that may cause permanent damage occured. CONCLUSION: Our results
      suggest that the percutaneous disc decompression is an effective and safe
      procedure for the treatment of pain caused by low thoracic intervertebral disc
      disease which did not respond to conservative treatments.

PMID- 30299262
TI  - Results of an internal audit on the survival of patients with uterine sarcoma.
AB  - OBJECTIVE: In the last 5 years there has been a lot of discussion about the
      surgical procedure for uterine fibroids and essentially also uterine sarcoma.
      Still there exist no reliable presurgical diagnostic tool to differentiate
      between benign fibroids and uterine sarcomas. The aim of this study was to
      confirm the suspected an association between intraoperative spread of tumor by
      morcellation and impaired outcome in sarcoma patients. MATERIAL AND METHODS:
      After local ethics commission positively reviewed the study protocol the
      oncological database of our university hospital was retrospectively reviewed for
      patients with uterine sarcomas over a time period of 13 years (2002-2015). Data
      was extracted from the medical files and survival information was collected by
      contacting patient's general practitioners if last follow-up-status was older
      than 6 months. For the analysis patients were split into two groups with either
      intrasurgical morcellation (M+) or no morcellation (M-) regarding information
      provided by the surgical report. RESULTS: Data on 57 uterine sarcoma patients was
      available for further analysis. The median age was 63years with a BMI of 27
      kg/m2. The sarcoma subtypes were 25 leiomyosarcoma (LMS), 19 carcinosarcoma (KS),
      9 endometriod stroma sarcoma (ESS), 3 adenosarcoma (AS) and one case without
      further differentiation. In the majority, no morcellation was done (44 patients
      in M- group) and 51 patients received open surgery (3 laparoscopic, 1 vaginal and
      2 incomplete surgeries). Median time of follow-up was 31 months. The disease free
      survival was 50.5 months and the cox regressions analysis showed a hazard ratio
      of 3.06 (no significant difference between the two subgroups (p=0.079; 95%-KI:
      0.9 - 10.6)). The overall survival was found to be 62.2 months and the cox
      regression analysis showed a hazard ratio of 3.216 with statistical
      significantdifference between the two subgroups (p=0.013; 95%-KI: 1.3 - 8.1).
      CONCLUSION: Despite the efforts to find a pre-surgical diagnostic tool, the
      clinical situation remains unsatisfactory. Overall sarcoma prevalence is low
      during the last 13 years at our university center, but morcellation occurred in a
      relevant portion of patients (13 out of 57). If a sarcoma is suspected or
      diagnosed the en-bloc resection of the uterus can prolong the survival. Thus,
      morcellation of the uterus and not the surgical technique (en-bloc resection) is
      the prognostic factor and should be avoided in any suspicious case.

PMID- 30299263
TI  - Selective fetal reduction in monochorionic twins: Preliminary experience.
AB  - OBJECTIVE: In complicated mono-chorionic twin pregnancies, vaso-occlusive
      techniques like bipolar cord coagulation (BPCC), radiofrequency ablation (RFA),
      interstitial laser ablation (ILA) of cord and fetoscopy guided cord coagulation
      with lasers are the methods proposed for selective fetal reduction. This study
      brings forth preliminary data of selective fetal reduction procedures at a
      tertiary care center in India. MATERIAL AND METHODS: This was a prospective
      observational study of 31 patients with complicated mono-chorionic twin
      pregnancies. Methods used were ILA, RFA and BPCC. Outcome measures included
      overall co-twin survival after selective feticide, survival rates with each
      method, miscarriage (defined as all fetal loss before 24 weeks), early fetal
      death (<24 hours after procedure) and late fetal death (>24hrs after the
      procedure) of co-twin. RESULTS: Technical success was achieved in 30/31(96.8%) of
      pregnancies. Over all take home baby rate was 63.3%. Live birth rates were 50%,
      71.4% and 75%with ILA, RFA and BPCC respectively. CONCLUSION: Data from initial
      cases of selective fetal reduction in complicated mono-chorionic twins suggests
      that these procedures are feasible but are associated with high adverse perinatal
      outcome.

PMID- 30299264
TI  - Oocyte Donors' Awareness on Donation Procedure and Risks: A Call for Developing
      Guidelines for Health Tourism in Oocyte Donation Programmes
AB  - Objective: In the recent years, oocyte donation programmes have widely spread
      worldwide becoming the drive of health tourism. In some countries the donation
      programmes are tightly regulated; whereas in some, the guidelines or regulations
      are not well defined. The aim of this study was to evaluate the donors' awareness
      of the donation programmes and the ethical consequences in enrolling these
      programmes. Material and Methods: A detailed questionnaire-based survey was
      conducted to evaluate the donors' main drive to get involved in the donation
      programme and the donor's knowledge and awareness of risk factors. Results:
      Majority of the donors (70%) were undergoing donation programmes for financial
      gains through compensation. The donors were especially not aware of the long-term
      medical risks and the possibility of identity exposure through genetic screening.
      Conclusion: The health professionals have the main duty to counsel the donors
      about the basic procedures and any possible problems they may face during the
      donation programmes. Reimbursement of oocyte donors is a slippery slope path in
      oocyte donation programmes. High compensation may make women to think that
      donation is a profession without considering possible risks. Furthermore, with
      the wider use of direct-toconsumer genetic testing, genetic anonymity may be at
      risk, thus the donors have to be counselled properly. Therefore, in this era of
      health tourism, it is crucial to set up well-defined counselling bodies in all
      oocyte donation centres and enable the donors to make an informed choice in
      becoming oocyte donors.

PMID- 30299266
TI  - Outcomes in Fournier's Gangrene Using Skin and Soft Tissue Sparing Flap
      Preservation Surgery for Wound Closure: An Alternative Approach to Wide Radical
      Debridement.
AB  - INTRODUCTION: Fournier's gangrene (FG) remains a forbidding necrotizing soft
      tissue infection (NSTI) that necessitates early recognition, prompt surgical
      excision, and goal-directed antibiotic therapy. Traditionally, surgical
      management has included wide radical excision for sepsis control, but this
      management often leaves large, morbid wounds that require complex wound coverage,
      prolonged hospitalizations, and/or delayed healing. OBJECTIVE: The purpose of
      this case series is to report the outcomes of FG using a surrogate approach of
      concurrent debridement of spared skin and soft tissue, negative pressure wound
      therapy (NPWT), and serial delayed primary closure (DPC). MATERIALS AND METHODS:
      A retrospective review of 17 consecutive patients with FG treated with concurrent
      skin and soft tissue sparing surgery, NPWT, and serial DPC at Miami Valley
      Hospital Regional Adult Burn and Wound Center (Dayton, OH) between 2008 and 2018
      was conducted. Patients were included if the following were noted: clinical
      suspicion of FG based on genital and perineal cellulitis, fever, leukocytosis,
      and confirmation of tissue necrosis upon surgical exploration. Patients not
      treated with skin sparing surgical debridement or wounds with an inability to
      maintain a NPWT dressing seal were excluded. RESULTS: The mean number of total
      surgeries including simultaneous debridement and reconstruction was 5.5. The
      average intensive care unit and hospital length of stay was 3.2 and 18.9 days,
      respectively. The average number of days from initial consult to wound closure
      was 24.3. The need for colostomy and skin grafts were nearly eliminated with this
      surrogate approach. Using this reproducible technique, DPC was achieved in 100%
      of patients. Only 11.8% (2/17) required split-thickness skin grafting as part of
      wound closure. The majority (9/17; 52.9%) were partially managed as an outpatient
      during wound closure. During staged DPC, the mean number of outpatient management
      days was 16.0. There were no mortalities in this series of patients. CONCLUSIONS:
      To the best of the authors' knowledge, this is the largest case series reported
      in the literature using skin and soft tissue sparing surgery for wound closure of
      a FG NSTI.

PMID- 30299267
TI  - Unusual Presentation of Deep Tissue Injuries: A Case Series.
AB  - Deep tissue injuries (DTIs) are the manifestation of multiple layers of tissue
      necrosis and are often secondary to chronic mechanical stress to an area of bony
      prominence. The prevalence of these injuries among the chronically ill and
      patients in long-term care require a strong understanding of their etiology and a
      highly sensitive identification algorithm. Although the National Pressure Ulcer
      Advisory Panel (NPUAP) has released new guidelines with accurate descriptions as
      to how these injuries present, there is a significant segment of patients that
      present atypically and, as such, the treatment plan and prognosis are difficult
      to predict based on physical presentation, which can lead to either delays in
      necessarily aggressive care or conversely an overzealous treatment plan in hopes
      of addressing a pathology that may be self-limiting. Three cases of patients with
      a DTI, in which the initial presentation was not typical (ie, as described by the
      current NPUAP staging system) and not an accurate diagnostic predictor of
      prognosis, are presented. These differences, their course of treatment, and a
      more comprehensive diagnostic approach will be discussed in the hopes of more
      accurately identifying these injuries with a focus on prediction of disease
      trajectory.

PMID- 30299265
TI  - The effect of nutrient supplementation in the management of polycystic ovary
      syndrome-associated metabolic dysfunctions: A critical review
AB  - Polycystic ovary syndrome (PCOS) is complex heterogeneous disorder that has
      several aspects in terms of pathology such as metabolic, endocrine, reproductive,
      and psychological. However, the etiology of PCOS remains poorly understood.
      Several studies suggest that insulin resistance and hyperandrogenism play a
      central role in the progression of PCOS pathophysiology. Therefore, common
      treatment strategies of PCOS are based on lifestyle modification, which include
      exercise, diet, and nutrient supplementation therapy. Recent studies have
      recommended some nutrients such as vitamins, minerals, and vitamin-like nutrients
      for the therapy of PCOS because each has at least one functional property in PCOS
      induced pathways. Therefore, it is claimed that the cause of PCOS could be
      vitamin or mineral deficiency. This review aims to provide a critical literature
      survey on nutritional supplementation for the treatment of PCOS-associated
      endocrine and metabolic dysfunctions and discuss the role of nutrients in the
      management of PCOS in view of the clinical trials and experimental studies.

PMID- 30299268
TI  - The fasting blood glucose and long non-coding RNA SNHG8 predict poor prognosis in
      patients with gastric carcinoma after radical gastrectomy.
AB  - This prospective study sought to evaluate the prediction of fasting blood glucose
      and long non-coding RNA (lncRNA) SNHG8 for the risk of gastric carcinoma
      mortality. A total of 217 gastric carcinoma patients underwent radical
      gastrectomy were included during 2012-16. The final follow-up was finished in
      January 2017. The aggregate hazard ratio(HR) demonstrated that poor prognosis of
      gastric carcinoma was associated with fasting blood glucose (HR= 1.29, P=0.037),
      SNHG8 expression(HR = 1.10, P= 0.009), positive distant metastasis(HR = 2.99, P=
      0.020), EBV positive (HR = 3.40, P=0.002), and tumor size more than 5.0 cm (HR =
      3.36, P= 0.005). In survival analysis, elevated fasting blood glucose (P =0.007)
      and high SNHG8 expression (P =0.007) were significantly associated with shorter
      survival times in gastric cancer. Significant multiplicative interaction was
      shown between fasting blood glucose and SNHG8 expression (chi-squared=7.81,
      Pmultiplicative =0.005), without statistical additive interaction. Fasting blood
      glucose and SNHG8 expression could predict poor prognosis after radical
      gastrectomy. LncRNA SNHG8 could be applied as a novel epigenetic molecular target
      in gastric carcinoma.

PMID- 30299270
TI  - Renin-Angiotensin Inhibition and Outcomes in Nursing Home Residents With Heart
      Failure.
AB  - BACKGROUND: Angiotensin-converting enzyme inhibitors or angiotensin receptor
      blockers (ACEIs-ARBs) improve outcomes in heart failure (HF). Less is known about
      this association in nursing home (NH) residents. METHODS: Of the 8024
      hospitalized HF patients, 542 were NH residents, of whom 250 received ACEIs-ARBs.
      We assembled a propensity score-matched cohort of 157 pairs of NH residents
      receiving and not receiving ACEIs-ARBs balanced on 29 baseline characteristics
      (mean age, 83 years, 74% women, 17% African American), in which we estimated
      hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated
      with ACEI-ARB use. We then checked for interaction in a matched cohort of 5130
      patients (378 were NH residents) assembled from the 8024 patients. RESULTS: Among
      314 matched NH residents, HRs (95% CIs) for 30-day all-cause readmission, HF
      readmission, and all-cause mortality were 0.78 (0.47-1.28), 0.68 (0.29-1.60), and
      1.26 (0.70-2.27), respectively. Respective HRs (95% CIs) at 1 year were 0.76
      (0.56-1.02), 0.68 (0.42-1.09), and 1.04 (0.78-1.38). Among 5130 matched patients,
      ACEI-ARB use was associated with a significantly lower risk of all outcomes at
      both times, with no significant interactions, except for 1-year mortality, which
      was only significant in the non-NH subgroup (P for interaction, 0.026).
      CONCLUSIONS: We found no evidence that the use of ACEIs or ARBs is associated
      with improved outcomes in patients with HF in the NH setting. However, we also
      found no evidence that this association is different in NH residents with HF
      versus non-NH patients with HF. Future larger studies are needed to demonstrate
      effectiveness of these drugs in the NH setting.

PMID- 30299269
TI  - A high glucose diet induces autophagy in a HLH-30/TFEB-dependent manner and
      impairs the normal lifespan of C. elegans.
AB  - A high-glucose diet (HGD) is associated with the development of metabolic
      diseases that decrease life expectancy, including obesity and type-2 diabetes
      (T2D); however, the mechanism through which a HGD does so is still unclear.
      Autophagy, an evolutionarily conserved mechanism, has been shown to promote both
      cell and organismal survival. The goal of this study was to determine whether
      exposure of Caenorhabditis elegans to a HGD affects autophagy and thus
      contributes to the observed lifespan reduction under a HGD. Unexpectedly,
      nematodes exposed to a HGD showed increased autophagic flux via an HLH-30/TFEB
      dependent mechanism because animals with loss of HLH-30/TFEB, even those with
      high glucose exposure, had an extended lifespan, suggesting that HLH-30/TFEB
      might have detrimental effects on longevity through autophagy under this stress
      condition. Interestingly, pharmacological treatment with okadaic acid, an
      inhibitor of the PP2A and PP1 protein phosphatases, blocked HLH-30 nuclear
      translocation, but not TAX-6/calcineurin suppression by RNAi, during glucose
      exposure. Together, our data support the suggested dual role of HLH-30/TFEB and
      autophagy, which, depending on the cellular context, may promote either
      organismal survival or death.

PMID- 30299272
TI  - Milnacipran for Postcoital Cephalgia and Premature Ejaculation.

PMID- 30299271
TI  - Antithrombotic Therapy and Outcomes of Patients With New-Onset Transient Atrial
      Fibrillation After ST-Segment Elevation Myocardial Infarction.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common complication of ST-segment
      elevation myocardial infarction (STEMI), and AF might require anticoagulant
      treatment in some conditions. STUDY QUESTION: There are no clear recommendations
      about vitamin K antagonist (VKA) use in patients with STEMI who complicated with
      new-onset transient AF. In this study, we examined the association of concomitant
      use of VKA and dual antiplatelet therapy (DAPT) with clinical outcomes of this
      patient population. STUDY DESIGN: A total of 4086 patients with STEMI who
      underwent primary percutaneous coronary intervention retrospectively
      investigated. Among these patients, a total of 286 patients who developed new
      onset transient AF during hospitalization were enrolled. VKA group consisted of
      116 patients treated with warfarin, aspirin, and clopidogrel, and DAPT group
      consisted of 170 patients treated with aspirin and clopidogrel. MEASURES AND
      OUTCOMES: One-year mortality, ischemic stroke, major, and minor bleeding were
      determined as clinical outcomes. RESULTS: Although VKA group had proportionally
      lower mortality (17.2% vs. 20.0%) and ischemic stroke (7.8% vs. 11.8%) compared
      with DAPT group, the differences did not reach to statistical significance,
      whereas the 1-year major bleeding had higher rates at VKA group and that had 3.5
      times higher major bleeding than DAPT group. This relationship was persisted
      after multivariable analysis (hazard ratio = 3.37, 95% CI, 1.76-10.04, P =
      0.012). CONCLUSIONS: There is not a widely accepted treatment algorithm in
      patients with STEMI who complicated with new-onset AF in clinical guidelines. The
      current study indicated that transient form of new-onset AF might not require
      long-term VKA. Besides, addition of VKA to DAPT therapy may increase the rates of
      major and minor bleeding.

PMID- 30299273
TI  - Radiocontrast-Induced Thyroid Storm.

PMID- 30299274
TI  - In Response.

PMID- 30299275
TI  - Brian Bateman, M.D., Recipient of the 2018 James E. Cottrell, M.D., American
      Society of Anesthesiologists Presidential Scholar Award: Erratum.

PMID- 30299276
TI  - Increased Health Care Utilization in Dementia Subtypes Before Diagnosis.
AB  - INTRODUCTION: Prior studies have reported higher health care utilization (HCU)
      leading up to diagnosis of the Alzheimer disease and related dementia (ADRD), but
      none have assessed variation in HCU by ADRD subtype or examined disease-specific
      HCU. The objectives of this study were to identify ADRD subtypes and: (1)
      characterize all-cause and (2) disease-specific HCU during the 3 years preceding
      diagnosis, and (3) determine if HCU varied by ADRD subtype. METHODS: We used data
      from the OptumLabs Data Warehouse 2008 to 2014 to identify ADRD subtypes (total
      N=36,838) using an algorithm based on temporal sequencing of diagnoses and
      provider type. Annual counts of all-cause and disease-specific HCU in each of the
      3 years preceding ADRD diagnosis were regressed on ADRD subtypes with mild
      cognitive impairment (MCI) as the reference group, year, and other variables.
      RESULTS: HCU increased over time, was highest in the outpatient setting, and
      varied by ADRD subtype. Compared with MCI, highest HCU was observed in vascular
      and nonspecific dementia. Compared with MCI, most subtypes had elevated disease
      specific HCU. DISCUSSION: Variation in HCU by ADRD subtype points to different
      pathways to diagnosis and patterns of use.

PMID- 30299277
TI  - Attenuation of glutamatergic and nitrergic system contributes to the
      antidepressant-like effect induced by capsazepine in the forced swimming test.
AB  - The transient receptor potential vanilloid 1 (TRPV1) can modulate stress-related
      behaviours, thus representing an interesting target for new antidepressant drugs.
      TRPV1 can trigger glutamate release and nitric oxide synthesis in the brain,
      mechanisms also involved in the neurobiology of depression. However, it is not
      known if these mechanisms are involved in TRPV1-induced behavioural effects.
      Therefore, the aim of this study was to verify if the antidepressant-like effect
      induced by a TRPV1 antagonist in mice submitted to the forced swimming test (FST)
      would be facilitated by combined treatment with neuronal nitric oxide synthase
      (nNOS) inhibition and N-methyl-D-aspartate (NMDA) blockade. Male Swiss mice were
      given (intracerebroventricular) injections of capsazepine (CPZ) (TRPV1 antagonist
      - 0.05/0.1/0.3/0.6 nmol/ul), and AP7 (NMDA antagonist - 1/3/10 nmol/ul) or N
      propyl-L-arginine (NPA, nNOS inhibitor - 0.001/0.01/0.1 nmol/ul), and 10 min
      later, submitted to an open field test, and immediately afterwards, to the FST.
      An additional group received coadministration of CPZ and AP7 or CPZ and NPA, in
      subeffective doses. The results demonstrated that CPZ (0.1 nmol/ul), AP7 (3
      nmol/ul) and NPA (0.01/0.1 nmol/ul) induced antidepressant-like effects.
      Moreover, coadministration of subeffective doses of CPZ and AP7 or CPZ and NPA
      induced significant antidepressant-like effects. Altogether, the data indicate
      that blockade of TRPV1 receptors by CPZ induces antidepressant-like effects and
      that both nNOS inhibition and NMDA blockade facilitate CPZ effects in the FST.

PMID- 30299278
TI  - Is Self-Reported Knee Stability Associated With Symptoms, Function, and Quality
      of Life in People With Knee Osteoarthritis After Anterior Cruciate Ligament
      Reconstruction?
AB  - OBJECTIVE: This study aimed to investigate the association of self-reported knee
      stability with symptoms, function, and quality of life in individuals with knee
      osteoarthritis after anterior cruciate ligament reconstruction (ACLR). SETTING:
      Cross-sectional. PARTICIPANTS: Twenty-eight individuals with knee osteoarthritis,
      5 to 12 years after ACLR. MAIN OUTCOME MEASURES: Self-reported knee stability was
      assessed using visual analogue scales (VAS) during hop for distance (HD), side-to
      side hop (SSH), and one-leg rise (OLR). Symptoms [Knee Injury and Osteoarthritis
      Outcome Score (KOOS) pain, Anterior Knee Pain Scale (AKPS), and International
      Knee Documentation Committee form], self-reported function (KOOS-sport/rec),
      performance-based function (hopping and OLR), and quality of life (KOOS-QOL) were
      assessed. K-means clustering categorized individuals into low (n = 8) and high
      self-reported knee stability (n = 20) groups based on participants' VAS scores
      during functional tasks. RESULTS: The low self-reported knee stability group had
      worse knee symptoms than the high self-reported knee stability group [KOOS-pain:
      mean difference -17 (95% confidence interval, -28 to -5); AKPS: -10 (-20 to -1)],
      and worse self-reported function [KOOS-sport/rec: -33 (-48 to -18)] and
      performance-based function [HD: -28 (-53 to -3); SSH: -10 (-20 to -1), OLR: -18 (
      32 to -50)]. CONCLUSION: Low self-reported stability is associated with worse
      symptoms, and worse self-reported and performance-based function. Further
      research is required to determine the causation relation of self-reported knee
      stability to knee symptoms and function in individuals with knee osteoarthritis
      after ACLR.

PMID- 30299279
TI  - Surgical Management of Placenta Accreta Spectrum.
AB  - This is a discussion of the standard surgical treatment of placenta accreta
      spectrum disorders including preoperative considerations, diagnostic imaging,
      surgical steps for cesarean hysterectomy, and postoperative management.

PMID- 30299280
TI  - Pathophysiology of Placenta Accreta Spectrum Disorders: A Review of Current
      Findings.
AB  - Current findings continue to support the concept of a biologically defective
      decidua rather than a primarily abnormally invasive trophoblast. Prior cesarean
      sections increase the risk of placenta previa and both adherent and invasive
      placenta accreta, suggesting that the endometrial/decidual defect following the
      iatrogenic creation of a uterine myometrium scar has an adverse effect on early
      implantation. Preferential attachment of the blastocyst to scar tissue
      facilitates abnormally deep invasion of trophoblastic cells and interactions with
      the radial and arcuate arteries. Subsequent high velocity maternal arterial
      inflow into the placenta creates large lacunae, destroying the normal
      cotyledonary arrangement of the villi.

PMID- 30299281
TI  - What is a Right Distal Fusion Level for Prevention of Sagittal Imbalance in
      Multilevel Posterior Cervical Spine Surgery: C7 or T1?
AB  - STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: To evaluate the
      sagittal alignment and T1 slope after multilevel posterior cervical fusion
      surgery depending on the distal fusion level; C7 or T1, and find out the
      appropriate distal fusion level. SUMMARY OF BACKGROUND DATA: The sagittal balance
      of the cervical spine is known to be affected by cervical lordosis and T1 slope.
      However, T1 slope is not a constant parameter that can be frequently changed
      after the surgery. Furthermore, useful studies to help guide surgeons in decision
      making as to the most appropriate distal level of fusion for cervical sagittal
      balance are very limited. MATERIALS AND METHODS: From 2014 to 2015, 50 patients
      who underwent multilevel posterior cervical fusion surgery were evaluated and
      followed up for >2 years. Group 1 was composed of 29 patients whose distal fusion
      level was C7. Group 2 was composed of 21 patients whose distal fusion level was
      T1. C1-C2 lordosis, C2-C7 lordosis, C2-C7 sagittal vertical axis (SVA), and T1
      slope were measured on preoperative and the last follow-up. RESULTS: In group 1,
      C2-C7 SVA (23.1->30.4 mm, P=0.043) was worsened, and T1 slope (22.3->32.9
      degrees, P=0.001) was increased after the surgery. In group 2, no significant
      change occurred in C2-C7 SVA after the surgery (25.3 ->23.6 mm, P=0.648). The
      last follow-up T1 slope was similar with preoperative T1 slope (22.7->21.8
      degrees, P=0.04) in group 2. CONCLUSIONS: This study showed that sagittal
      alignment became worse after the multilevel posterior cervical surgery when
      distal fusion level was stopped at C7, which was associated with increase of T1
      slope. However, when we extended the distal fusion level to T1, T1 slope was not
      changed after the surgery. Therefore, sagittal alignment was maintained after the
      surgery. On the basis of the results of this study, we recommend distal fusion
      extends to T1. LEVEL OF EVIDENCE: Level III.

PMID- 30299282
TI  - Do Cervical Spine Surgery Patients Recall Their Preoperative Status?: A Cohort
      Study of Recall Bias in Patient-reported Outcomes.
AB  - STUDY DESIGN: This is a prospective cohort study. OBJECTIVE: To characterize the
      accuracy of patient recollection of preoperative symptoms after cervical spine
      surgery. SUMMARY OF BACKGROUND DATA: Recall bias is a well-known source of
      systematic error. The accuracy of patient recall after cervical spine surgery
      remains unknown. METHODS: Consecutive patients undergoing cervical spine surgery
      for myelopathy or radiculopathy were enrolled. Neck and arm numeric pain scores
      and Neck Disability Indices were recorded preoperatively. Patients were asked to
      recall their preoperative status at either short (<1 y) or long-term (>=1 y)
      follow-up. Actual and recalled scores were compared using paired t tests and
      relations were quantified using the Pearson correlation coefficients.
      Multivariable linear regression was used to identify factors impacting
      recollection. RESULTS: In total, 73 patients with a mean age of 58.2 years were
      included. Compared with their preoperative scores, patients showed significant
      improvement in neck pain [mean difference (MD)=-2.9; 95% confidence intervals
      (CIs), -3.5 to -2.3], arm pain (MD, -3.4; 95% CI, -4.0 to -2.8), and disability
      (MD, -12.4%; 95% CI, -16.9 to -7.9). Patient recollection of preoperative status
      was significantly more severe than actual for neck pain (MD, +1.5; 95% CI, 0.8
      2.2), arm pain (MD, +2.3; 95% CI, 1.6-3.0), and disability (MD, +5.8%; 95% CI,
      2.4-9.2). Moderate correlation between actual and recalled scores with regard to
      neck (r=0.41), arm (r=0.50) pain, and disability (r=0.67) was seen. This was
      maintained across age, sex, and time between date of surgery and recollection.
      Over 30% of patients switched their predominant symptom from neck-to-arm pain or
      vice versa on recall of their preoperative symptoms. CONCLUSIONS: Relying on
      patient recollection does not provide an accurate measure of preoperative status
      after cervical spine surgery. Prospective and not retrospective collection of
      patient-reported outcomes remain the gold standard to measure and interpret
      outcomes after cervical spine surgery. Recall bias has the potential to affect
      patient satisfaction and requires further study.

PMID- 30299283
TI  - Endothelial Cell Loss in Obstetric Forceps-Related Corneal Injury: A Longitudinal
      Specular Microscopic Study.
AB  - PURPOSE: To assess the impact of ocular trauma associated with obstetric forceps
      delivery on the corneal endothelium in children. METHODS: Five patients who
      attended the Hospital for Sick Children, Toronto, between 2013 and 2016 with a
      diagnosis of unilateral obstetrical forceps-related corneal injury were included.
      Clinical presentation, best-corrected visual acuity, corneal endothelial cell
      density (ECD, cells/mm), and measures of cellular morphology were obtained.
      RESULTS: The mean follow-up duration was 30 +/- 10 months. Mean ECD in the
      affected eye at initial assessment was significantly lower than that of the
      fellow eye (2576 +/- 733 vs. 3481 +/- 288 cells/mm, P = 0.02). At final follow
      up, mean ECD was 3293 +/- 175 and 1907 +/- 524 cells/mm in the normal and
      affected eyes, respectively (P = 0.004). The mean annual rate of the ECD decrease
      was higher in the affected eyes than in the normal eyes (9.1% +/- 4.2% vs. 2.0%
      +/- 2.5%), although this difference was not statistically significant (P = 0.06).
      CONCLUSIONS: In children with forceps-related corneal injury, lower ECD with a
      higher annual decrease can be assessed with specular microscopy for risk
      stratification and parental counseling purposes.

PMID- 30299284
TI  - Nurse Decision Making and Attitudes About Circuit Disconnection During Ventilator
      Therapy at a Swedish Neonatal Intensive Care Unit.
AB  - BACKGROUND: There are many challenges to providing care to infants in need of
      ventilator therapy. Yet, few studies describe the practical handling of the
      ventilator circuit during nursing care. PURPOSE: To describe neonatal intensive
      care unit (NICU) nurses' decision making regarding whether or not to disconnect
      the ventilator circuit when changing the infant's position and to investigate the
      grounds for their decisions. METHODS: A descriptive questionnaire study with both
      quantitative and qualitative elements was conducted. In 2015, a convenience
      sample of nurses working in an NICU completed a questionnaire including both
      closed-ended and open-ended, free-text questions. Answers to the closed-ended
      questions were analyzed with descriptive statistics, whereas answers to the free
      text questions were analyzed using qualitative content analysis. RESULTS: Nurses'
      decisions on whether to disconnect or keep the ventilator circuit closed were
      based on the infant's needs for ventilator support. The nurses gave several
      reasons and motivations both for why they disconnected the circuit and for why
      they did not. The handling of the circuit and the reasons and motivations given
      were inconsistent among the nurses. IMPLICATIONS FOR PRACTICE: This study
      highlights the need for continuous, repetitive education and training for NICU
      nurses, as well as demonstrating the importance of clear and distinct guidelines
      and working methods regarding the care of infants on ventilator support.
      IMPLICATIONS FOR RESEARCH: Future research should continue to find ways of
      working and handling an infant on ventilator support that are least harmful to
      the infant.

PMID- 30299285
TI  - Is a Cephalomedullary Nail Durable Treatment for Patients With Metastatic
      Peritrochanteric Disease?
AB  - BACKGROUND: Although cephalomedullary nail fixation is often used for metastatic
      peritrochanteric lesions of the femur, there is concern regarding the durability
      of the implant in comparison to endoprosthetic reconstruction. Previous studies
      have reported the proportion of patients who undergo reoperation for loss of
      stability, but the adequacy of the construct has not been critically evaluated in
      a competing risk analysis that incorporates death of the patient in the
      calculation. QUESTIONS/PURPOSES: (1) What is the cumulative incidence of
      reoperation of cephalomedullary nails with death as a competing risk for
      metastatic lesions of the proximal femur? (2) What is the survival of patients
      with metastases to the proximal femur after cephalomedullary nailing? (3) What
      clinical factors are associated with implant stability in these patients?
      METHODS: Between 1990 and 2009, 11 surgeons at one center treated 217 patients
      with cephalomedullary nails for metastatic proximal femoral lesions. This
      represented 40% (217 of 544) of the patients undergoing surgery for metastases in
      this location during the study period. In general, we used cephalomedullary nails
      when there was normal bone in the femoral head, no fracture in the neck, and a
      moderate-sized lesion; we favored bipolar hemiarthroplasty for femoral neck
      fractures and disease affecting the femoral head; finally, we used proximal
      femoral endoprosthetic replacement for large lesions with severe bone
      destruction. A retrospective study was conducted of 199 patients with
      cephalomedullary nails for peritrochanteric metastases from 1990 to 2009.
      Pathologic fracture, defined as a breach in cortex with a clear fracture line
      either with or without displacement, was present in 61 patients. The most common
      primary cancers were breast (42 of 199 patients [21%]), lung (37 of 199 patients
      [18%]), and renal cell (34 of 199 patients [17%]). A competing risk analysis was
      performed to describe the cumulative incidence of implant revision. Patient
      overall survival was assessed by Kaplan-Meier survivorship. A univariate analysis
      was performed to determine whether there was an association between revision
      surgery and various patient factors, including tumor histology, pathologic
      fracture, cementation, and radiation. RESULTS: Loss of implant stability
      necessitating revision surgery occurred in 19 of 199 patients (10%). In a
      competing risk analysis with death of the patient as the competing event, the
      cumulative incidence of revision surgery was 5% (95% confidence interval [CI], 3%
      9%) at 12 months and 9% (95% CI, 5%-13%) at 5 years. Using Kaplan-Meier analysis,
      the overall patient survival was 31% (95% CI, 25%-37%) at 12 months and 5% (95%
      CI, 3%-9%) at 60 months. Patients with lung cancer had the shortest overall
      survival of 11% (95% CI, 1%-21%) at 12 months, and patients with multiple myeloma
      had the longest overall survival of 71% (95% CI, 49%-94%) at 12 months (p <
      0.001). Duration of patient survival beyond the median 7 months was the only
      factor associated with a greater likelihood of revision surgery. Factors not
      associated with revision included tumor histology, pathologic fracture, closed
      versus open nailing, cementation, gender, age, and postoperative radiation.
      CONCLUSIONS: The competing risk analysis demonstrates a relatively low cumulative
      incidence of reoperation and suggests that cephalomedullary nailing is reasonable
      for patients with moderate-sized proximal femoral metastasis not affecting the
      femoral head. For the large majority of patients, the construct achieves the goal
      of stabilizing the femur for the duration of the patient's life. Longer patient
      survival was associated with greater risk of revision surgery, but no particular
      tumor histology was found to have a greater cumulative incidence of reoperation.
      Future work with a larger number of patients and stricter surgical indications
      may be needed to corroborate these findings. LEVEL OF EVIDENCE: Level III,
      therapeutic study.

PMID- 30299286
TI  - Reply to the Letter to the Editor: Five Hundred Fifty-five Retrieved Metal-on
      metal Hip Replacements of a Single Design Show a Wide Range of Wear, Surface
      Features, and Histopathologic Reactions.

PMID- 30299287
TI  - From Bench to Bedside: A Little Dab Will Do You Good? Topical Prevention of
      Surgical Site Infections.

PMID- 30299288
TI  - Advances in management of nonvariceal upper gastrointestinal bleeding.
AB  - PURPOSE OF REVIEW: To review new advances in managing nonvariceal upper
      gastrointestinal hemorrhage. RECENT FINDINGS: Implementation of various scoring
      systems in combination with video capsule endoscopy assists in stratifying and
      managing nonvariceal upper gastrointestinal bleeding. New techniques such as
      thermocoagulation and hemoclips are useful to treat bleeding. SUMMARY: The
      advancement of methods and procedures in managing nonvariceal upper
      gastrointestinal bleeding has decreased mortality of patients presenting with
      this type of hemorrhage. In this chapter, we will be discussing various scores to
      stratify nonvariceal upper gastrointestinal bleeding and techniques to stop
      bleeding.

PMID- 30299289
TI  - Xenobiotic and endobiotic handling by the mucosal immune system.
AB  - PURPOSE OF REVIEW: Mucosal immune cells in the intestinal tract are continuously
      exposed to a barrage of both foreign and endogenously generated metabolites,
      termed xenobiotics, and endobiotics, respectively. This review summarizes recent
      insights into the mechanisms by which xenobiotics and endobiotics regulate
      intestinal immunity and inflammation. RECENT FINDINGS: The community of enteric
      microbes (i.e., microbiota) has profound impacts on the development and function
      of the mucosal immune system. The composition and function of gut microbiota is
      dynamically regulated by diet, and this interplay dictates which and how many
      immunomodulatory xenobiotics are present in the intestine. Microbiota also
      regulate the concentration and composition of circulating bile acids, an abundant
      class of liver-derived endobiotics with pleotropic immunoregulatory activities. A
      growing body of literature is emerging that sheds new light on the mechanisms by
      which xenobiotics and endobiotics interact with germline-encoded receptors and
      transporters to shape mucosal immune function. SUMMARY: The complex and dynamic
      interplay among xenobiotics, endobiotics, and the mucosal immune system is a new
      frontier in mucosal immunology that is proving fruitful for the discovery of
      novel and pharmacologically accessible mechanisms with relevance to human
      inflammatory diseases.

PMID- 30299290
TI  - Mucosal immune responses to fungi and the implications for inflammatory bowel
      disease.
AB  - PURPOSE OF REVIEW: The intestinal microbiota plays a central role in inflammatory
      diseases of the gut. Although most investigations regarding how the mucosal
      immune system interacts with the microbiota have focused on bacteria, recent
      studies are elucidating the additional role of commensal fungi in health and
      disease in the gut. RECENT FINDINGS: New technical approaches are defining the
      makeup of the fungal communities in the intestines of humans and mice. The
      reported composition of these communities is influenced by the approaches used to
      define the fungi. Changes in the intestinal mycobiota are associated with gut
      inflammation in patients with inflammatory bowel disease and in mouse models of
      colitis. Recent studies are beginning to elucidate the mechanisms by which the
      mucosal immune system interacts with and is influenced by intestinal fungi.
      SUMMARY: Studies clearly demonstrate the presence of intestinal fungi and
      document the ability of the mucosal immune system to recognize and respond to
      fungi. Future studies will further investigate whether intestinal fungi directly
      influence intestinal disease and what cellular, molecular, and genetic mechanisms
      contribute.

PMID- 30299291
TI  - Impact of ovarian function suppression in premenopausal women with estrogen
      receptor-positive early breast cancer.
AB  - PURPOSE OF REVIEW: This manuscript aims at providing an updated overview on the
      role of adding ovarian function suppression to tamoxifen or an aromatase
      inhibitor as adjuvant endocrine therapy in premenopausal women with estrogen
      receptor-positive early breast cancer. RECENT FINDINGS: Until recently, tamoxifen
      alone was the only recommended adjuvant treatment option for premenopausal women
      with estrogen receptor-positive disease. However, recent important evidence has
      contributed to significantly modify the endocrine treatment landscape in this
      setting. SUMMARY: With the only exception of patients with low-risk clinical
      pathological features characterized by excellent survival outcomes with tamoxifen
      alone, the use of ovarian function suppression is to be considered standard of
      care for most of premenopausal women with estrogen receptor-positive disease.
      Regarding the choice of its best partner as endocrine agent, the available data
      suggest that the higher the risk of disease recurrence the larger benefit can be
      observed with a more profound estrogen deprivation that can be obtained with
      ovarian function suppression and an aromatase inhibitor as compared to ovarian
      function suppression and tamoxifen. Despite the significant improvement in our
      understanding on the role of ovarian function suppression in this setting,
      several unanswered questions remain and further research efforts are needed in
      the field.

PMID- 30299292
TI  - Risk stratification in early breast cancer in premenopausal and postmenopausal
      women: integrating genomic assays with clinicopathological features.
AB  - PURPOSE OF REVIEW: There is growing consensus that genomic assays provide useful
      complementary information to clinicopathological features in oestrogen receptor
      positive breast cancers. Here, ongoing research with multigene tests used for
      postmenopausal breast cancer and new emerging prognostic and predictive markers
      for pre and postmenopausal women are summarised. RECENT FINDINGS: Results of the
      TAILORx trial have shown that women with an intermediate risk score do not
      benefit from adjuvant chemotherapy. Prosgina has been further investigated in a
      contemporary patient population in postmenopausal women and its use has been
      extended for premenopausal women. The EndoPredict was extensively used in
      decision-impact studies showing that its use can potentially reduce the need for
      adjuvant chemotherapy. Several new genomic assays have been developed, with some
      of them showing promising use for women with early oestrogen receptor-positive
      breast cancer. SUMMARY: New areas of research for prediction of recurrence and
      risk stratification involve the development of immune gene signatures that carry
      modest but significant prognostic value. The recent expansion of high-throughput
      technology platforms including circulating tumour DNA/RNA and microRNA offer new
      opportunities to improve prediction models, particularly in women with oestrogen
      receptor-negative disease and premenopausal women. Genomic assays have clearly
      improved prognostication of early oestrogen receptor-positive breast cancer but
      it is clear that standard clinicopathological parameters are still very important
      when identifying patient for adjuvant chemotherapy.

PMID- 30299293
TI  - Relocation of an Infected Cardiac Pacemaker Generator Under Ultrasound-Guided
      Pectoralis Nerve Block: A Case Study.
AB  - Reports on pacemaker placement/relocation surgery under pectoralis nerve block
      are limited. We herein report a case involving a 74-year-old woman with an
      infected cardiac pacemaker generator who underwent pacemaker relocation surgery
      under an ultrasound-guided pectoralis nerve block. On preoperative evaluation,
      she had congestive heart failure, type 2 diabetes mellitus, and a pacer-dependent
      heart rhythm. She was considered to be at high risk for general anesthesia. Thus,
      an ultrasound-guided pectoralis nerve block was planned. The surgery was
      completed successfully, without notable complications. Our findings might help in
      the management of patients who require pacemaker implantation/relocation.

PMID- 30299294
TI  - Challenges in Grading Low-Flow, Low-Gradient Aortic Stenosis.

PMID- 30299295
TI  - Presumed Malignant Hyperthermia Treated During Cardiopulmonary Bypass in a
      Pediatric Patient Undergoing Aortic Valve Replacement: A Case Report.
AB  - There are no case reports of malignant hyperthermia in pediatric patients treated
      on cardiopulmonary bypass (CPB). We report the case of a 10-year-old boy
      undergoing aortic valve replacement. The patient developed progressive
      tachycardia and hypercarbia. In addition, EtCO2 and PaCO2 were equal and
      myoglobinuria was suspected given darkened urine. Numerous dantrolene boluses
      were given on CPB, and a dantrolene infusion was started. The patient's base
      deficit and creatine phosphokinase normalized by postoperative day 2. This case
      demonstrates the importance of expeditious diagnosis of malignant hyperthermia,
      and the need for additional dantrolene when treating patients whose blood volume
      is diluted on CPB.

PMID- 30299296
TI  - Dual Epidural Catheter Therapy for Abdominal Surgery Pain: 2 Case Reports.
AB  - Dual epidural catheter (DEC) therapy improves postoperative pain control in
      scoliosis correction surgery, esophagectomies, and labor. Reports about the use
      of a second epidural catheter to improve pain control after abdominal surgeries
      are sparse. We describe the successful use of unplanned DEC therapy in 2 complex
      pain patients who underwent large exploratory laparotomies. In both patients, the
      addition of the second catheter led to improved pain control and mobility and
      reduced side effects from adjuvant intravenous analgesics. DEC therapy merits
      consideration as an additional tool for managing postoperative pain after large
      abdominal surgeries despite existing incomplete epidural analgesia.

PMID- 30299297
TI  - In Response.

PMID- 30299298
TI  - Evaluation of 30 Day Readmissions After Index Ventricular Assist Device
      Implantation in the United States.
AB  - Ventricular assist device (VAD) implantation has improved quality of life and
      short-term survival for advanced heart failure patients. There are limited data
      from single-center studies addressing the characteristics and etiologies of 30
      day readmissions after VAD implant. We used the Nationwide Readmissions Database
      (NRD) 2014 to identify insertion of implantable heart assist system during index
      admission. Primary and secondary outcomes were 30 day readmissions and leading
      etiologies, respectively. We analyzed 1,481 patients who received VAD during the
      primary admission of whom 1,315 patients survived to hospital discharge
      (mortality rate 11.2%), and 60.6% were discharged to a nursing facility. One
      hundred and thirty-one (10.0%) patients were readmitted within 30 days of primary
      hospitalization. Leading etiologies of 30 day readmission were bleeding (24%),
      heart failure (18%), and device complications (14%). Mean length of stay during
      readmission was 13.8 days with a mortality rate of 2.1%. Fifty percent of 30 day
      readmissions were readmitted from day 22 to 30. Variables for predictors of 30
      day readmissions were not statistically significant. By identifying
      gastrointestinal bleeding, heart failure, and device complications as leading
      etiologies of 30 day readmission post-VAD implantation, providers can potentially
      modify practices to prevent hospital readmissions, decreasing cost of care, and
      improving the quality of life of patients.

PMID- 30299299
TI  - Pharmacokinetics of Sildenafil in Patients with a Left Ventricular Assist Device:
      A Word of Caution.
AB  - We compared maximal plasma concentrations (Cmax) of sildenafil and metabolite n
      desmethyl sildenafil in 12 inpatients with left ventricular assist devices
      (LVADs) on sildenafil (60 mg/day) to the reference range. Sildenafil Cmax (156.8
      +/- 124.5 ng/ml) was elevated in 66% of patients, with a two to fivefold increase
      over the upper limit of the reference range in 25% of patients. Metabolite Cmax
      (133.3 +/- 102.0 ng/ml) was elevated in 75% of patients, with a three to
      sevenfold increase over the upper limit of the reference range in 40% of
      patients. Patients with heart failure and LVADs are at increased risk of
      concentrated-related sildenafil adverse events.

PMID- 30299300
TI  - Bivalirudin and ECLS: Commentary and Considerations.

PMID- 30299302
TI  - Bivalirudin in Extracorporeal Life Support: Response and Considerations.

PMID- 30299301
TI  - Management of RVAD Thrombosis in Biventricular HVAD Supported Patients: Case
      Series.
AB  - Patients with biventricular assist devices (BIVAD) are severely critically ill
      compared with patients who receive left ventricular assist device (LVAD) support
      alone and portend a significant risk for greater adverse events including pump
      thrombosis (PT). Current approaches to treat PT are limited to LVAD with variable
      outcomes depending on the management strategy implemented. Moreover the
      management of PT in patients with BIVAD support, specifically to the right
      ventricular assist device (RVAD), is unknown. We describe the first care series
      to date on the management of PT in patients with durable right ventricular assist
      device and their outcomes.

PMID- 30299303
TI  - Chronic In Vivo Test of a Right Heart Replacement Blood Pump for Failed Fontan
      Circulation.
AB  - An implantable rotary blood pump was developed to provide long-term mechanical
      right heart support for patients who have failing Fontan circulation. The
      objective of this study was to evaluate the pump in vivo in a 30 day sheep study.
      Pump speed was set at 3,900 rpm for the duration of the study, and pump power was
      between 4.3 and 4.6 W. The pump inlet pressures for the superior vena cava (SVC)
      and inferior vena cava (IVC) were 14 +/- 15 and 11 +/- 15 mm Hg, respectively,
      over the duration of the study. Hematocrit remained stable at 30% +/- 4%. Partial
      thromboplastin time (PTT) steadily increased from 30 s preoperatively to a high
      of 59 s on postoperative day 20, while prothrombin time (PT) remained at 20 +/- 2
      s for the duration of the study. The implantation and postoperative recovery were
      successful, and the animal demonstrated normal physiologic pulmonary and venous
      pressures and cardiac output. On pump inspection, the IVC and SVC inlets were
      completely clear of any deposits, but there were small thrombi (approximately 0.5
      mm diameter) between each of the three rotor blades and along 20% of the parting
      line of the two volute halves. A complete right heart bypass was performed,
      postoperative recovery was successful, and the pump demonstrated adequate
      circulatory support and normal physiologic pulmonary and venous pressures. This
      study was the first successful test of a right heart replacement device in a
      chronic animal study.

PMID- 30299304
TI  - Use of an Ecological Momentary Assessment Application to Assess the Effects of
      Auricular Point Acupressure for Chronic Low Back Pain.
AB  - The purpose of this pilot study was to assess the feasibility and usability of an
      ecological momentary assessment smartphone application. The app collected real
      time data on chronic low back pain and time-contingent ecological momentary
      assessment surveys during a 4-week auricular point acupressure intervention, and
      on the consistency between recalled and momentary clinical measures. Eighteen
      participants received auricular point acupressure treatment weekly for 4 weeks.
      Each participant was provided a smartphone with the ecological momentary
      assessment application installed, along with instructions for use. The primary
      outcomes comprised pain intensity, pain interference with daily activity, sleep
      quality score, and medication usage. System Usability Scale and adherence were
      also measured. According to the results, the rate of adherence for completion of
      the random ecological momentary assessment survey was 87%. The usability score
      for the ecological momentary assessment application was reported as 78. The
      average recalled pain intensity was higher than the mean momentary pain
      intensity. Self-reported average pain interference with daily activities showed a
      similar result. Spearman rank correlation coefficients were greater than +0.70; P
      < .01 for the associations among recalled and momentary measurements. In
      conclusion, the study demonstrated promising adherence rates and supported the
      usability and feasibility of using an ecological momentary assessment application
      on a smartphone to collect real-time data on chronic lower back pain, which
      eliminated recall bias.

PMID- 30299305
TI  - Filipino Nurses' Use of Smartphones in Clinical Settings.
AB  - While previous research has examined specific ways that nurses have used
      smartphones for work purposes in clinical settings, large-sample quantitative
      studies are limited, particularly in Asia. To address this research gap, this
      study provided a ranking on how nurses have used their smartphones for work
      purposes in clinical settings and identified differences based on demographic and
      organizational factors. In January to June 2017, a pen-and-paper survey was
      administered to 517 staff nurses employed in 19 tertiary-level general hospitals
      in Metro Manila, Philippines. Results show that nurses frequently used their
      smartphones to exchange voice calls and text messages with other nurses and
      doctors. Results also showed that specific items reflecting the use of
      smartphones for communication purposes differed according to gender, age,
      hospital ownership, nursing area, number of patients handled in last shift, and
      presence of a hospital-provided mobile phone. Next, some items for information
      seeking purposes differed according to highest educational attainment and years
      of clinical experience. Moreover, some items for documentation purposes differed
      according to age, hospital ownership, and number of patients handled in last
      shift. Overall, the results of this study can be used to guide policies on the
      use of smartphones in clinical settings.

PMID- 30299306
TI  - Towards the integration of pharmacogenetics in psychiatry: a minimum, evidence
      based genetic testing panel.
AB  - PURPOSE OF REVIEW: The implementation of pharmacogenetic testing in psychiatry is
      underway but is not yet standard protocol. Barriers to pharmacogenetics becoming
      standard practice are the lack of translation of evidence-based recommendations
      and standardization of genetic testing panels. As for the latter, there are
      currently no regulatory standards related to the gene and allele content of
      testing panels used to derive medication selection and dosing advice. To address
      these barriers, we summarize the current gene-drug interaction knowledgebase and
      proposed a minimum gene and allele set for pharmacogenetic testing in psychiatry.
      RECENT FINDINGS: The Pharmacogenomics Knowledgebase has cataloged 448 gene-drug
      interactions relevant to psychiatry based on the current scientific literature,
      drug labels, and pharmacogenetic-based implementation guidelines. A majority of
      these interactions involved two cytochrome P450 enzymes (CYP2D6 and CYP2C19) and
      antidepressant medications, however, CYP2C9, HLA-A, and HLA-B are relevant to
      mood stabilizers/anticonvulsants. SUMMARY: On the basis of evidence base, we
      proposed a minimum gene and allele set for pharmacogenetic testing in psychiatry
      that includes 16 variant alleles within five genes (CYP2C9, CYP2C19, CYP2D6, HLA
      A, HLA-B). The intent is to assist clinicians in judging the gene and allele
      content of pharmacogenetic tests and to facilitate pharmacogenetic testing as a
      standard protocol and companion tool for psychotropic medication selection and
      dosing.

PMID- 30299307
TI  - Schema therapy conceptualization of personality functioning and traits in ICD-11
      and DSM-5.
AB  - PURPOSE OF REVIEW: Schema therapy conceptualizes personality disorders in terms
      of modes and underlying schemas. This article reviews the literature on schema
      therapy conceptualization of personality disorder functioning and traits, and
      proposes how these findings apply to novel personality disorder classification in
      ICD-11 and the DSM-5 Alternative Model of Personality Disorders (AMPD). RECENT
      FINDINGS: Maladaptive schemas and modes are generally associated with personality
      dysfunction and traits in conceptually coherent ways. The healthy adult mode, a
      transdiagnostic core concept in schema therapy, corresponds to the ICD-11 and DSM
      5-AMPD features of core personality functioning. Modes and underlying schemas
      substantially overlap with specific ICD-11 and DSM-5-AMPD traits, which denote
      individual themes and styles of personality dysfunction. SUMMARY: The dimensional
      personality disorder framework in ICD-11 and DSM-5-AMPD is largely compatible
      with the schema therapy model. The ICD-11 and DSM-5-AMPD provide a scientifically
      derived and theory-free framework for all practitioners, which may be connected
      to clinical theory of schema therapy in a coherent manner. Level of personality
      functioning can be conceptualized as healthy adult functioning (e.g. sense of
      identity, self-worth, emotion regulation, intimacy, and fulfillment), which
      inform intensity of treatment. Trait qualifiers can be conceptualized by
      associated modes (e.g., compliant surrender) and underlying schemas (e.g.
      abandonment), which inform focus and style of treatment.

PMID- 30299308
TI  - Dialysis catheters in the ICU: selection, insertion and maintenance.
AB  - PURPOSE OF REVIEW: Choosing the best catheter for renal replacement therapy (RRT)
      is not an easy task. Beyond catheter length, many of its properties can influence
      effectiveness of the RRT session. Maintenance between sessions, particularly the
      locking solution, also impacts catheter lifespan and infection rates. RECENT
      FINDINGS: Many innovations in dialysis catheters have been proposed by the
      industry over the past decade, including the material used, the shape of the
      lumens and the position of the inflow and outflow holes. Impregnated catheters
      have also been developed to prevent catheter-related infections. Many locking
      solutions are available, either for maintaining catheter patency or for
      preventing infections. SUMMARY: Although studies conducted in the specific
      context of the ICU are still scarce, some conclusions can be drawn. Catheter
      length must be adapted to the insertion site to reach an area of high blood flow.
      Kidney-shape lumens appear to be less thrombogenic and seem to prevent catheter
      dysfunction. Catheter tip and lumen holes also affect catheter function. For
      catheter locking, 4% citrate appears nowadays as one of the best options, but
      taurolidine-based solutions are also interesting.

PMID- 30299309
TI  - Noninvasive ventilation as acute therapy.
AB  - PURPOSE OF REVIEW: Noninvasive ventilation (NIV) is widely used in ICU patients
      to treat or to prevent acute respiratory failure. Whereas its physiological
      effects are clearly beneficial in hypercapnic patients, it could be deleterious
      in hypoxemic patients without hypercapnia. RECENT FINDINGS: NIV should be
      cautiously used in patients with de-novo respiratory failure, the vast majority
      of whom meet the criteria for acute respiratory distress syndrome. Spontaneous
      breathing with high tidal volumes may worsen lung injury in these patients, and
      recent findings suggest that NIV may increase the risk of mortality. Even though
      high-flow oxygen therapy is increasingly applied in this context, NIV remains
      recommended for management of immunocompromised patients with acute respiratory
      failure. NIV should be the first-line oxygenation strategy in patients with acute
      hypercapnic respiratory failure when pH is equal to or below 7.35. Prophylactic
      NIV prevents respiratory failure after extubation of patients at high risk of
      reintubation. SUMMARY: Most previous studies have compared NIV with standard
      oxygen, and recent recommendations have been established from these findings.
      Given the growing use of high-flow oxygen therapy, new studies are needed to
      compare NIV versus high-flow oxygen therapy so as to better define the
      appropriate indications for each treatment.

PMID- 30299310
TI  - Major surgery and the immune system: from pathophysiology to treatment.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the
      immune response to major surgery, and the ways in which it may be modulated to
      improve postoperative outcomes. RECENT FINDINGS: Data from patients who have
      undergone a variety of tissue injuries (surgery, burns, sepsis, trauma) have
      shown the presence of a conserved 'genomic storm' that alters the leukocyte
      transcriptome, with upregulation of the innate immune response and concomitant
      downregulation of the adaptive immune response. The innate and adaptive immune
      systems are often regarded largely distinct. However, more recent evidence
      suggests there are critical connections between the two arms of the immune
      response, whereby innate immune cells are able to suppress the adaptive response.
      SUMMARY: The immune system is critical to the host response to tissue injury
      occurring due to surgery. However, the physiological processes required to
      resolve the surgical insult can also contribute to sequelae such as cognitive
      decline, pneumonia and acute kidney injury. Our understanding of the immune
      pathogenesis underlying these complications is improving, leading to interest in
      the development of immunomodulatory therapies, which aim to permit host defence
      whilst ameliorating postoperative complications.

PMID- 30299311
TI  - Perioperative management of obese patient.
AB  - PURPOSE OF REVIEW: The volume of bariatric and nonbariatric surgical procedures
      on obese patients is dramatically increasing worldwide over the past years. In
      this review, we discuss the physiopathlogy of respiratory function during
      anesthesia in obese patients, the stratification of perioperative risk to develop
      intraoperative and postoperative pulmonary complications, the optimization of
      airway management, and perioperative ventilation, including postoperative
      respiratory assistance. RECENT FINDINGS: Scores have been proposed to stratify
      the risk of surgical patients, some of which were specifically developed for
      obese patients. Most scores identify obstructive sleep apnea and elevated BMI as
      independent risk factors. Obese patients might be at risk of difficult intubation
      and mask ventilation, and also of developing postoperative pulmonary
      complications. Intraoperative ventilation settings affect clinical outcome, but
      the optimal ventilation strategy is still to be determined. Opioid-free regimens
      are being widely investigated. Postoperative monitoring and respiratory
      assistance are necessary in selected patients. Early mobilization and
      physiotherapy are mandatory. SUMMARY: Obese patients are at higher risk of
      perioperative complications, mainly associated with those related to the
      respiratory function. An appropriate preoperative evaluation, intraoperative
      management, and postoperative support and monitoring is essential to improve
      outcome and increase the safety of the surgical procedure.

PMID- 30299312
TI  - How to optimize critical care resources in surgical patients: intensive care
      without physical borders.
AB  - PURPOSE OF REVIEW: Timely identification of surgery patients at risk of
      postoperative complications is important to improve the care process, including
      critical care. This review discusses epidemiology and impact of postoperative
      complications; prediction scores used to identify surgical patients at risk of
      complications, and the role of critical care in the postoperative management. It
      also discusses how critical care may change, with respect to admission to the
      ICU. RECENT FINDING: Optimization of postoperative outcome, next to preoperative
      and intraoperative optimization, consists of using risk scores to early identify
      patients at risk of developing complications. Critical care consultancy should be
      performed in the ward after surgery, if necessary. ICUs could work at different
      levels of intensity, but remain preferably multidisciplinary, combining care for
      surgical and medical patients. ICU admission should still be considered for those
      patients at very high risk of postoperative complications, and for those
      receiving complex or emergency interventions. SUMMARY: To optimize critical care
      resources for surgery patients at high risk of postoperative complications, the
      care process should not only include critical care and monitoring in ICUs, but
      also strict monitoring in the ward. Prediction scores could help to timely
      identify patients at risk. More intense care (monitoring) outside the ICU could
      improve outcome. This concept of critical care without borders could be
      implemented in the near future to optimize the local resources and improve
      patient safety. Predict more, do less in ICUs, and more in the ward.

PMID- 30299313
TI  - Emergencies in critical care: improving care by learning how to use old therapies
      better.

PMID- 30299314
TI  - Renal replacement therapy in the ICU: continued controversy despite recent
      advances.

PMID- 30299315
TI  - Risk factors for extrahepatic cholangiocarcinoma: a case-control study in China.
AB  - To investigate risk factors for extrahepatic cholangiocarcinoma (ECC) in China. A
      total of 200 ECC cases and 200 matched control were included in the study. The
      presence of cigarette smoking, alcohol drinking, choledocholithiasis, primary
      sclerosing cholangitis, liver fluke infection (Clonorchis sinensis), diabetes
      mellitus, was investigated through clinical records. Blood from all cases was
      tested for hepatitis B surface antigen. Odds ratios (OR) and 95% confidence
      intervals (CIs) were estimated using conditional logistic regression. Compared
      with controls, ECC patients had a higher prevalence of cigarette smoking (61.0
      vs. 47.0%, P=0.007), alcohol drinking (17.5 vs. 3.5%, P<0.000), and
      choledocholithiasis (6.0 vs. 1.0%, P=0.011). By multivariate analysis, the
      significant risk factors for the development of ECC were current smoking
      (OR=1.90, 95% CI=1.08-3.34), heavy alcohol drinking (OR=2.08, 95% CI=1.39-3.13),
      and choledocholithiasis (OR=6.68, 95% CI=1.48-30.27). The prevalence of hepatitis
      B virus infection, diabetes mellitus were not significantly different between
      cases and controls. These findings suggest that smoking, alcohol drinking, and
      choledocholithiasis are positive risk factors for the development of ECC in
      China.

PMID- 30299316
TI  - Vitamin D receptor expression and serum 25(OH)D concentration inversely
      associates with burden of neurofibromas.
AB  - Vitamin D and its receptor may play a role in preventing tumor development and
      progression. As such antineoplastic effects are expected to be weak and to act
      over long periods, conditions with increased tumor incidence, such as the
      neurofibromatosis type 1 (NF1), provide suitable study models. We previously
      found an inverse correlation of serum 25(OH)D concentration with number of
      neurofibromas in NF1. Here we aim to further explore the role of the vitamin D
      receptor. A total of 141 adult NF1 patients were included in the study. For 101
      of them, serum vitamin 25(OH)D data were available. From 87 patients, blood
      samples were obtained in PaxGene tubes containing a reagent to stabilize RNA
      immediately. mRNA of the vitamin D receptor (VDR) gene (coding for the vitamin D
      receptor) was measured by means of RT-PCR. Correlation of laboratory data with
      NF1-related tumors was statistically evaluated. Vitamin D receptor in NF1-tumors
      was examined by means of immunohistochemistry using an antibody against the
      vitamin D1 receptor. The number of dermal neurofibromas was significantly
      inversely correlated with VDR mRNA level and with serum 25(OH)D concentration in
      NF1 patients. In contrast, plexiform neurofibroma and malignant peripheral nerve
      sheath tumor did not correlate with these two parameters. Immunostaining did not
      detect vitamin D receptor in NF1-tumors. Both vitamin D and its receptor may play
      a role in suppressing the development of neurofibromas. Sustaining 25(OH)D at an
      adequate level may contribute to controlling neurofibromas and possibly also
      other tumors. This is especially important for individuals with lower expression
      of VDR.

PMID- 30299318
TI  - Expanding adolescent access to hormonal contraception: an update on over-the
      counter, pharmacist prescribing, and web-based telehealth approaches.
AB  - PURPOSE OF REVIEW: Hormonal contraceptives are largely responsible for recent
      declines in unintended adolescent pregnancies, with oral contraceptives being the
      most commonly used. Young people face multiple barriers to accessing effective
      contraception in clinical settings. This article reviews innovations in
      contraceptive access. RECENT FINDINGS: The three biggest innovations are over-the
      counter oral contraceptives (OTC-OCs), pharmacist-prescribing, and web-based
      telehealth platforms. In many countries, oral contraceptives are available OTC,
      and FDA trials for OTC-OCs are underway in the United States. Many states have
      passed legislation allowing pharmacists to prescribe contraceptives after a brief
      health screening. Web-based telehealth platforms also provide prescription
      contraceptive access. There is a small but growing body of literature that
      demonstrates young people's interest in, and capacity to consent to, hormonal
      contraceptives in nontraditional settings. State-to-state variability in minor
      consent, pharmacist prescribing, and telehealth laws act as barriers to young
      people's access to these newer options. SUMMARY: Access to hormonal contraception
      is expanding outside of clinical settings, reducing barriers. Adolescents' unique
      needs should be considered in the design, implementation, and evaluation of these
      new approaches. More data is needed to ensure that adolescents are not excluded
      from expanded contraceptive access options, as they are disproportionately
      affected by unintended pregnancy.

PMID- 30299317
TI  - The challenge of cardiomyopathies and heart failure in pregnancy.
AB  - PURPOSE OF REVIEW: To discuss the risk preexisting or new onset
      cardiomyopathy/heart failure (CMP/heart failure) in pregnant woman, and recent
      insights regarding their management and therapy. RECENT FINDINGS: Recent data
      from the European Registry on Pregnancy and Heart disease of the European Society
      of Cardiology (ROPAC) suggest that, after an adequate prepregnancy evaluation in
      specialized centres, the vast majority of pregnancies are safe for both mother
      and foetus. A tailored approach is required according to cardiac phenotype (i.e.
      type of cardiomyopathy), clinical and functional status, and new potential
      treatments (i.e. bromocriptine in patients with peripartum cardiomyopathy).
      SUMMARY: In clinical practice, prepregnancy cardiac evaluation is mandatory,
      including evaluation of the clinical status, standard ECG (and 24-48 h
      monitoring, whenever required), and imaging, to define the individual risk
      profile. In presence of severe symptoms (advanced New York Heart Association
      class), cardiac dysfunction (moderate-severe reduced ejection fraction),
      haemodynamic load (left ventricular outflow tract obstruction, pulmonary
      hypertension), pregnancy is contraindicated. A tailored monitoring is warranted
      in other cases (mild-moderate risk pregnancies). Likewise, in women who develop
      PPCM, a risk stratification and tailored monitoring and therapy should be
      achieved by an expert, multidisciplinary team, including cardiologists,
      gynaecologists, obstetricians, genetic counsellor, and psychologists.

PMID- 30299319
TI  - Clinical significance of cerebroplacental ratio.
AB  - PURPOSE OF REVIEW: Two-thirds of the pregnancies complicated by stillbirth
      demonstrate growth restriction. Identification of the foetus at risk of growth
      restriction is essential to reduce the risk of stillbirth. The aim of this review
      is to critically appraise the current evidence regarding clinical utility of
      cerebroplacental ratio (CPR) in antenatal surveillance. RECENT FINDINGS: The CPR
      has emerged as an assessment tool for foetuses at increased risk of growth
      disorders. CPR is a better predictor of adverse events compared with middle
      cerebral artery or umbilical artery Doppler alone. The predictive value of CPR
      for adverse perinatal outcomes is better for suspected small-for-gestational age
      foetuses compared with appropriate-for-gestational age (AGA) foetuses. CPR could
      be useful for the risk stratification of small-for-gestational age foetuses to
      determine the timing of delivery and also to calculate the risk of intrapartum
      compromise or prolonged admission to the neonatal care unit. Although there are
      many proposed cut-offs for an abnormal CPR value, evidence is currently lacking
      to suggest the use of one cut-off over another. CPR appears to be associated with
      increased risk of intrapartum foetal compromise, abnormal growth velocity, and
      lower birthweight in AGA foetuses as well. Moreover, birthweight differences are
      better explained with CPR compared to other factors such as ethnicity. However,
      the role of CPR in predicting adverse perinatal outcomes such as acidosis or low
      Apgar scores in AGA foetuses is yet to be determined. SUMMARY: CPR appears to be
      a useful surrogate of suboptimal foetal growth and intrauterine hypoxia and it is
      associated with a variety of perinatal adverse events.

PMID- 30299320
TI  - The patient perspective: perceptions of the quality of the abortion experience.
AB  - PURPOSE OF REVIEW: Abortion services are essential in sexual and reproductive
      health and should be held to the same standards as other health services. Patient
      (or person)-centeredness is a key dimension of healthcare quality that
      incorporates the perspectives of patients in care provision. The purpose of this
      review is to summarize studies published in the last year examining women's
      experiences with abortion care and to describe facilitators and barriers to
      person-centered care. RECENT FINDINGS: Considering person-centeredness in
      abortion care using dimensions of dignity, autonomy, privacy, communication,
      social support, supportive care and health facility environment allows for
      critical evaluation of data describing women's experiences with abortion and
      postabortion services. Review of the available literature shed light on the
      impact of social stigma, health policy and abortion restrictions on women's
      abortion experiences. SUMMARY: Considering multiple domains and varied settings,
      current data suggest abortion services worldwide generally fail to provide person
      centered care. Institutions and providers may be limited in their ability to
      provide patient-centered abortion care because of deeply embedded social stigma,
      institutional regulations and legal restrictions.

PMID- 30299321
TI  - Advances in the management of early pregnancy loss.
AB  - PURPOSE OF REVIEW: To describe recent advances in management of early pregnancy
      loss. RECENT FINDINGS: Addition of mifepristone to current protocols for medical
      management of miscarriage increases effectiveness of a single dose of misoprostol
      and significantly reduces subsequent aspiration procedures. Women with an
      incomplete evacuation after medical management may be treated expectantly with
      similar rates of complete expulsion compared with surgical management at 6 weeks.
      As cytogenetic analysis improves, analysis of products of conception can be
      performed whether collected after surgical or medical management and is an
      efficient strategy in starting a recurrent pregnancy loss work-up. For those
      seeking pregnancy after miscarriage, conception immediately following an early
      pregnancy loss is not associated with increased risk of subsequent miscarriage.
      However, recent studies suggest that the original intendedness of the pregnancy
      resulting in miscarriage does not predict future reproductive goals of the woman,
      so family planning should be discussed at the time of miscarriage. SUMMARY:
      Miscarriage is a common experience among reproductive-aged women and advances in
      medical management and modern-day aspiration techniques make the use of the sharp
      curette obsolete.

PMID- 30299322
TI  - Pelvic floor disorders in women with gynecologic malignancy.
AB  - PURPOSE OF REVIEW: This article serves as an update on issues relating to the
      intersection of pelvic floor disorders and gynecology oncology. RECENT FINDINGS:
      Gynecologic cancer survivors experience pelvic floor disorders (PFDs) at a higher
      rate than their age-matched peers, often because of shared risk factors and as
      sequelae of cancer treatment. Concomitant pelvic floor and oncologic surgery can
      serve as a method to promote quality of life. Studies have demonstrated
      concomitant surgery to be well tolerated in appropriately selected patients, but
      only about 2% of oncologic surgeries are coordinated to include the treatment of
      PFDs. Conversely, women undergoing surgery for PFD have a low, but real risk of
      occult malignancy. Therefore, preoperative counseling is warranted in select
      populations. This article will discuss the management of concurrent PFDs and
      gynecologic malignancies. SUMMARY: Healthcare providers should be familiar with
      screening, management and referral of women with pelvic floor disorders in the
      gynecologic oncology population.

PMID- 30299323
TI  - Ergonomics in gynecologic surgery.
AB  - PURPOSE OF REVIEW: Work-related musculoskeletal disorders (WMSDs) are prevalent
      among surgeons and result in significant disability. We aimed to review the
      English-language literature regarding ergonomic risk, prevalence of WMSDs, and
      unique ergonomic considerations of gynecologic surgery. RECENT FINDINGS: Surgeon
      WMSDs are prevalent, with rates ranging from 66 to 94% for open surgery, 73-100%
      for conventional laparoscopy, 54-87% for vaginal surgery, and 23-80% for robotic
      assisted surgery. Risk factors for injury in open surgery include use of loupes,
      headlamps, and microscopes. Unique risks in laparoscopic surgery include table
      and monitor position, long-shafted instruments, and poor instrument handle
      design. In vaginal surgery, improper table height and twisted trunk position
      create injury risk. Although robotic surgery offers some advantages in neck and
      shoulder strain, it remains associated with trunk, wrist, and finger strain.
      SUMMARY: WMSDs are prevalent among surgeons but have received little attention
      because of under-reporting of injury and logistical constraints of studying
      surgical ergonomics. Future research must aim to develop objective surgical
      ergonomics instruments and guidelines and to correlate ergonomics assessments
      with pain and tissue-level damage in surgeons with WMSDs. Ergonomics training
      should be developed and implemented in order to protect surgeons from
      preventable, potentially career-altering injuries.

PMID- 30299324
TI  - Psychological burden of haematological cancer on patient and family: is it time
      for a multisystem approach?
AB  - PURPOSE OF REVIEW: Literature addressing the psychological impact of
      haematological cancers on patients and their families is sparse. New evidence
      might prompt a change in approach to the assessment and management of
      psychological burden. RECENT FINDINGS: The diagnosis, treatment and surveillance
      of haematological cancers often have a profound psychological impact on patients
      and their families and can result in clinically significant problems and
      increased carer stress. These may manifest at any stage from diagnosis to death
      or living as a survivor. Some high-risk subgroups have been identified. SUMMARY:
      The range of diagnostic groups, wide range of data analysis time-points relative
      to time of diagnosis, heterogeneity of outcome measures and differing
      methodologies (mainly prevalence studies) confound generalization of the
      findings. Targeted screening of the most at-risk subpopulations at times of
      greatest risk seems sensible to facilitate early intervention; further work is
      required to establish how often to screen and the best way of doing that. None of
      these articles define thresholds for intervention. Clearly more psychological
      support is needed for patients with haematological cancers and their families,
      but these articles do not provide evidence to suggest what this should comprise.
      There remains a need for large, longitudinal multicentre studies.

PMID- 30299325
TI  - Endpoints in clinical trials in cancer cachexia: where to start?
AB  - PURPOSE OF REVIEW: The lack of agreement and knowledge of optimal endpoints in
      cachexia trials have impeded progress in finding interventions counteracting the
      devastating effects cancer cachexia has on morbidity and mortality. An endpoint
      should both be sensitive enough to detect change and specific enough not to be
      influenced by other conditions or treatments. RECENT FINDINGS: There is a wealth
      of potential and applied endpoints in trials investigating cachexia. As of today,
      there is no generally acknowledged consensus, but assessments of key factors such
      as body composition should continue to be applied. However, the impact and effect
      size necessary to achieve clinical benefit using these endpoints are not clear.
      Further, the use of other endpoints assessing physical function, symptom
      evaluation and quality of life remains to be elucidated. SUMMARY: It is essential
      that endpoints are clinically relevant and further research is therefore needed
      to develop endpoints that are meaningful for patients with cachexia.

PMID- 30299326
TI  - Managing anaemia in bone marrow failure syndromes.
AB  - PURPOSE OF REVIEW: Anaemia is a common haematological presentation in patients
      with bone marrow failure, yet a challenging condition to treat. As anaemia has a
      direct impact on the patient's symptoms, managing anaemia in the common bone
      marrow failure conditions, such as myelodysplastic syndrome will help to improve
      the quality of life. This review discusses the available treatment options and
      the benefit of improving the haemoglobin level. RECENT FINDINGS: Managing anaemia
      effectively has shown to improve the patient outcome, yet treatment option remain
      limited. Recently, activin inhibitors such as Luspatercept have shown to be
      effective in patients' refractory to ESAs and further clinical trials are ongoing
      to explore this further. SUMMARY: Transfusion still remains the mainstay of
      treatment in patients not suitable, lost response or refractory to erythropoiesis
      stimulating agents (ESAs). Majority of these patients are not suitable for
      definite treatment options such as bone marrow transplantation. The aim of
      treatment remains improving the quality of life and newer therapeutic options may
      offer better and more sustained response.

PMID- 30299327
TI  - NACNS Newsletter: President's Message.

PMID- 30299328
TI  - Clinical Nurse Specialists International.

PMID- 30299329
TI  - A Season of Self-destruction-The Current Suicide Epidemic in Older Adults:
      Evidence to Consider Before Writing the Prescription.

PMID- 30299330
TI  - Yoga Treatment for Chronic Nonspecific Low Back Pain.

PMID- 30299331
TI  - Data and the Nurse: Combining Expertise in Clinical Domains and Data Analytics.

PMID- 30299332
TI  - A Clinical Nurse Specialist-Led Initiative to Reduce Deficits in Tube Feeding
      Administration for the Surgical and Trauma Populations.
AB  - PURPOSE/OBJECTIVES: The purpose of this clinical nurse specialist-led initiative
      was to redefine the standard of care to reduce the deficit that exists between
      the daily amount of tube feedings prescribed versus received by patients in a
      surgical-trauma intensive care unit. DESCRIPTION OF THE PROJECT: Nutrition plays
      a vital role in health and wellness. Although nutritional recommendations are not
      always met by individuals on a daily basis-the presence of in-hospital
      malnutrition presents greater risks and complications after a surgery or
      traumatic event. An evidence-based algorithm for initiating and maintaining tube
      feedings was developed and incorporated into morning bedside report. A
      preintervention and postintervention chart analysis was done to calculate the
      amount of tube feedings received by patients during their first 5 days of
      admission. OUTCOMES: Preintervention data revealed that 29 patients received a
      mean 49.8% (SD, 21.6%) of tube feedings prescribed, and postintervention data
      showed 31 patients received 60.4% (SD, 18.5%) of tube feedings prescribed (P =
      .04). CONCLUSION: Through the implementation of a tube feeding algorithm, there
      was a reduction of tube feed interruptions and volume deficits during the first 5
      days of admission.

PMID- 30299333
TI  - Alcohol Withdrawal Assessment Tool: Validity and Reliability Testing in Acute
      Care.
AB  - PURPOSE/AIMS: The purpose of this study was to validate a tool to assess alcohol
      withdrawal in acute care patients. Study aims included (1) establish content
      validity, (2) examine criterion-related validity, (3) test interrater
      reliability, and (4) assess nurse usability. DESIGN: A psychometric research
      study was designed to evaluate the Alcohol Withdrawal Assessment Tool. METHODS:
      Validation was conducted using an expert panel to determine content validity. The
      Clinical Institute Withdrawal Assessment for Alcohol-Revised was used as
      comparison for the criterion related validity. Interrater reliability was
      determined by having 2 investigators simultaneously complete the assessment on
      the same patients. Usability was determined using a Likert scale survey. RESULTS:
      The average age of participants was 53 years, with a range of 27 to 81 years.
      Interrater reliability was supported by a kappa statistic range of 0.61 to
      0.6957, and content validity was supported by a content validity index of 1.0.
      Criterion-related validity was supported with a Pearson r correlation of 0.665 (P
      < .000). Of nurses surveyed, all answered agree or strongly agree to the
      usability survey. CONCLUSIONS: The assessment tool may be an effective
      alternative to utilize in the acute care setting. It is easy to use and drives
      frequency of assessment and appropriate pharmacologic treatment.

PMID- 30299334
TI  - Clinical Nurse Specialists' Perceptions of a Mental Health Patient Portal.
AB  - PURPOSE: The purposes of this study were to explore clinical nurse specialists'
      views of the potential influence of a mental health portal on nursing practice
      and to identify portal implementation strategies. METHODS: A qualitative
      descriptive approach was used. Semistructured interviews were conducted with 5
      clinical nurse specialists. Two independent coders conducted an inductive content
      analysis of the transcribed interviews to generate codes describing patterns in
      the data to identify originating themes. RESULTS: The content analysis uncovered
      the following 4 themes: (1) implementation strategies, (2) nurse likelihood to
      recommend, (3) impact on nursing practice, and (4) perceived influence on
      patients. CONCLUSION: Direct care nurses may benefit from education and coaching
      on how to document in the record using patient-centered language that is
      understandable to patients who may be reading it. In addition, the use of patient
      portals should be designed to fit into nurses' existing clinical workflows.
      Finally, more research is needed to identify the benefits and unintended
      consequences of patient portals within a mental health context.

PMID- 30299335
TI  - A Best Practice Initiative to Optimize Transfer of Young Adults With Osteogenesis
      Imperfecta From Child to Adult Healthcare Services.
AB  - PURPOSE: The aims of this study were (1) to review the current body of knowledge
      on the transition experiences of adolescents with osteogenesis imperfecta (OI)
      and appraise the evidence available on transfer summary tools, (2) to develop
      guidelines for the successful transition of adolescents with OI from child to
      adult healthcare services, and (3) to create a transfer tool tailored to
      adolescents with OI. DESIGN AND METHODS: This knowledge synthesis study was
      overseen by an interprofessional expert task force at Shriners Hospitals for
      Children-Canada and entailed (1) review of the literature, (2) development of
      guidelines, and (3) creation of a tool. RESULTS: The tool was created from
      evidence compiled from case reports, clinical examples, and nonexperimental
      studies. CONCLUSION: The transfer tool proposes guidelines designed to facilitate
      a smooth transition from child to adult healthcare services. It also offers
      creation of a clinically meaningful, person-focused, OI transfer tool that may in
      turn help improve the transition experience for adolescents. This study
      significantly contributes to the dearth of literature on transition experiences
      in OI and on transfer tools in general. Future research is needed to evaluate the
      implementation and evaluation of the OI transfer tool in practice.

PMID- 30299336
TI  - Caring for the Body, Mind, and Spirit.

PMID- 30299337
TI  - A Season of Self-destruction-The Current Suicide Epidemic in Older Adults:
      Evidence to Consider Before Writing the Prescription.

PMID- 30299338
TI  - Biomarkers for Radiation Biodosimetry and Injury Assessment after Mixed-field
      (Neutron and Gamma) Radiation in the Mouse Total-body Irradiation Model.
AB  - The risk of potential radiation exposure scenarios that include detonation of
      nuclear weapons, terrorist attacks on nuclear reactors, and the use of
      conventional explosives to disperse radioactive substances has increased in
      recent years. The majority of radiation biodosimetry and countermeasure studies
      have been performed using photon radiation even though many exposure scenarios
      predict mixed-field (neutron and photon) radiation. Hence, there is a need to
      evaluate biomarkers and accurately determine exposure levels of mixed-field
      combinations of neutrons and photons for an individual. These biomarkers will be
      critical for biodosimetry triage, treatment, and follow-up visits with such
      individuals. We evaluated the utility of multiple blood biomarkers for early
      response assessment of radiation exposure using a mouse (B6D2F1, males and
      females) total-body irradiation model exposed to a mixed-field (neutrons and
      gamma rays) using the Armed Forces Radiobiology Research Institute's Mark F
      nuclear research reactor. Total-body irradiation was given as a single exposure
      over a dose range from 1.5 to 6 Gy, dose rates of 0.6 and 1.9 Gy min, and
      different proportions of neutrons and gammas: either (67% neutrons + 33% gammas)
      or (30% neutrons + 70% gammas). Blood was collected 1, 2, 4, and 7 d after total
      body irradiation. Radiation-responsive protein biomarkers were measured using the
      Meso Scale Diagnostics' high-throughput MULTI-ARRAY plate-format platform
      (QuickPlex 120 Imager) and enzyme-linked immunosorbent assay kits. Results
      demonstrate (1) dose- and time-dependent changes in fms-related tyrosine kinase 3
      ligand, interleukins IL-5, IL-10, IL-12, and IL-18, granulocyte and granulocyte
      macrophage colony-stimulating factors, thrombopoietin, erythropoietin, acute
      phase proteins (serum amyloid A and lipopolysaccharide binding protein), surface
      plasma neutrophil (CD45) and lymphocyte (CD27) markers, ratio of CD45 to CD27,
      and procalcitonin; (2) dose- and time-dependent changes in blood cell counts
      (lymphocytes, neutrophils, platelets, red blood cells, and ratio of neutrophils
      to lymphocytes); (3) levels of IL-18, granulocyte and granulocyte-macrophage
      colony-stimulating factors, serum amyloid A, and procalcitonin were significantly
      higher in animals irradiated with 67% neutrons + 33% gammas compared to those
      irradiated with 30% neutrons + 70% gammas (p < 0.015), while no significant
      differences (p > 0.114) were observed in hematological biomarker counts; (4)
      exposure with 3-fold difference in dose rate (0.6 or 1.9 Gy min) revealed no
      significant differences in hematological and protein biomarker levels (p >
      0.154); and (5) no significant differences in hematological and protein biomarker
      levels were observed in the sex-comparison study for any radiation dose at any
      time after exposure (p > 0.088). Results show that the dynamic changes in the
      levels of selected hematopoietic cytokines, organ-specific biomarkers, and acute
      phase protein biomarkers reflect the time course and severity of acute radiation
      syndrome and may function as prognostic indicators of acute radiation syndrome
      outcome. These studies supplement an ongoing effort to deliver U.S. Federal Drug
      Administration-approved biodosimetry capabilities, which assess mixed-field
      radiation exposure.

PMID- 30299339
TI  - Mapping 241Am Spatial Distribution Within Anatomical Bone Structures Using
      Digital Autoradiography.
AB  - Digital autoradiography with the ionizing radiation quantum imaging detector is
      used at the US Transuranium and Uranium Registries for visualizing the
      microdistribution of alpha particles from Am and quantifying the activity. The
      radionuclide spatial distribution was investigated within cortical and trabecular
      regions of bone samples from US Transuranium and Uranium Registries case 0846.
      Multiple specimens from the humerus proximal end, humerus proximal shaft, and
      clavicle acromial end were embedded in plastic, and 100-MUm-thick sections were
      taken and imaged using the ionizing radiation quantum imaging detector. The
      detector images were superimposed on the anatomical structure images to visualize
      Am distribution in cortical bone, trabecular bone, and trabecular spongiosa.
      Activity concentration ratios were used to characterize Am distribution within
      different bone regions. The trabecular-to-cortical bone and trabecular-spongiosa
      to-cortical bone activity concentration ratios were quantified in both humerus
      and clavicle. The ionizing radiation quantum imaging detector results were in
      agreement with those obtained from radiochemical analysis of the remaining bone
      specimens. The results were compared with International Commission on
      Radiological Protection default biokinetic model predictions. Digital
      autoradiography was proven to be an effective method for microscale heterogeneous
      distribution studies where traditional counting methods are impractical.

PMID- 30299340
TI  - Opioid Prescribing Practices of Orthopaedic Surgeons: Results of a National
      Survey.
AB  - INTRODUCTION: Opioids are widely used after orthopaedic procedures. Nonmedical
      opioid use is a growing public health issue. METHODS: An anonymous online survey
      was distributed by e-mail to the orthopaedic societies of all 50 states and
      several large private practices to assess practicing orthopaedic surgeons' opioid
      prescribing practices. RESULTS: A total of 555 orthopaedic surgeons practicing in
      37 states responded. The most commonly prescribed opioid for both teenagers and
      adults was hydrocodone/acetaminophen. Of note, 42.3% reported that a patient they
      have prescribed opioids for developed an opioid dependency, whereas 35.3% do not
      believe that opioid use is a problem in their practice. Of note, 30.3% reported
      prescribing refills, and factors significantly associated with increased
      prescribing of refills included a greater number of years in practice (P < 0.001)
      and practicing in a suburban rather than an urban or rural environment (P =
      0.03). CONCLUSION: Orthopaedic surgeons rarely prescribe any refills, tend to
      prescribe less opioids to teenagers than adults, and prescribe fairly uniformly
      for patients who are treated nonsurgically or undergo minor or arthroscopic
      surgery. They exhibit considerable variation in prescribing for fractures and
      major procedures.

PMID- 30299341
TI  - Effect of Obesity on Perioperative Complications, Hospital Costs, and Length of
      Stay in Patients With Open Ankle Fractures.
AB  - INTRODUCTION: The objective of this study was to examine the effect of obesity on
      perioperative complications and the cost of surgical management of open ankle
      fractures. METHODS: This study examined data from the National Inpatient Sample.
      The primary outcome variables assessed were occurrence of any complication,
      complication subtype, length of stay, and total hospital costs. RESULTS: Patients
      with obesity accounted for 10.1% (n = 8.972) of the total cohort. After adjusting
      for patient and hospital characteristics, patients with obesity exhibited higher
      odds of any complication, as well as longer length of stay and higher total
      costs. CONCLUSION: As our understanding of the association between complications
      and cost of managing open ankle fractures in patients with obesity improves,
      future research should strive to improve patient outcomes and decrease cost of
      care through efforts made to prevent complications in patients with obesity.

PMID- 30299342
TI  - Redundant Information Is Sometimes More Beneficial Than Spatial Information to
      Understand Speech in Noise.
AB  - OBJECTIVES: To establish a framework to unambiguously define and relate the
      different spatial effects in speech understanding: head shadow, redundancy,
      squelch, spatial release from masking (SRM), and so on. Next, to investigate the
      contribution of interaural time and level differences to these spatial effects in
      speech understanding and how this is influenced by the type of masking noise.
      DESIGN: In our framework, SRM is uniquely characterized as a linear combination
      of head shadow, binaural redundancy, and binaural squelch. The latter two terms
      are combined into one binaural term, which we define as binaural contrast: a
      benefit of interaural differences. In this way, SRM is a simple sum of a monaural
      and a binaural term. We used the framework to quantify these spatial effects in
      10 listeners with normal hearing. The participants performed speech
      intelligibility tasks in different spatial setups. We used head-related transfer
      functions to manipulate the presence of interaural time and level differences. We
      used three spectrally matched masker types: stationary speech-weighted noise, a
      competing talker, and speech-weighted noise that was modulated with the broadband
      temporal envelope of the competing talker. RESULTS: We found that (1) binaural
      contrast was increased by interaural time differences, but reduced by interaural
      level differences, irrespective of masker type, and (2) large redundancy (the
      benefit of having identical information in two ears) could reduce binaural
      contrast and thus also reduce SRM. CONCLUSIONS: Our framework yielded new
      insights in binaural processing in speech intelligibility. First, interaural
      level differences disturb speech intelligibility in realistic listening
      conditions. Therefore, to optimize speech intelligibility in hearing aids, it is
      more beneficial to improve monaural signal-to-noise ratios rather than to
      preserve interaural level differences. Second, although redundancy is mostly
      ignored when considering spatial hearing, it might explain reduced SRM in some
      cases.

PMID- 30299343
TI  - Factors Affecting Sound-Source Localization in Children With Simultaneous or
      Sequential Bilateral Cochlear Implants.
AB  - OBJECTIVES: The study aimed to determine the effect of interimplant interval and
      onset of profound deafness on sound localization in children with bilateral
      cochlear implants, controlling for cochlear implant manufacturer, age, and time
      since second implant. DESIGN: The authors conducted a retrospective,
      observational study using routinely collected clinical data. Participants were
      127 bilaterally implanted children aged 4 years or older, tested at least 12 mo
      post- second implant. Children used implants made by one of three manufacturers.
      Sixty-five children were simultaneously implanted, of whom 43% were congenitally,
      bilaterally profoundly deaf at 2 and 4 kHz and 57% had acquired or progressive
      hearing loss. Sixty-two were implanted sequentially (median interimplant interval
      = 58 mo, range 3-143 mo) of whom 77% had congenital and 23% acquired or
      progressive bilateral profound deafness at 2 and 4 kHz. Children participated in
      a sound-source localization test with stimuli presented in a random order from
      five loudspeakers at -60, -30, 0, +30, and +60 degrees azimuth. Stimuli were
      prerecorded female voices at randomly roved levels from 65 to 75 dB(A). Root mean
      square (RMS) errors were calculated. Localization data were analyzed via
      multivariable linear regression models, one applied to the whole group and the
      other to just the simultaneously? implanted children. RESULTS: Mean RMS error was
      25.4 degrees (SD = 12.5 degrees) with results ranging from perfect accuracy to
      chance level (0-62.7 degrees RMS error). Compared with simultaneous implantation,
      an interimplant interval was associated with worse localization by 1.7 degrees
      RMS error per year (p < 0.001). Compared with congenital deafness, each year with
      hearing thresholds better than 90 dB HL at 2 and 4 kHz bilaterally before
      implantation led to more accurate localization by 1.3 degrees RMS error (p <
      0.005). Every year post-second implant led to better accuracy by 1.6 degrees RMS
      error (p < 0.05). Med-El was associated with more accurate localization than
      Cochlear by 5.8 degrees RMS error (p < 0.01) and with more accurate localization
      than Advanced Bionics by 9.2 degrees RMS error (p < 0.05). CONCLUSIONS:
      Interimplant interval and congenital profound hearing loss both led to worse
      accuracy in sound-source localization for children using bilateral cochlear
      implants. Interimplant delay should therefore be minimized for children with
      bilateral profound hearing loss. Children presenting with acquired or progressive
      hearing loss can be expected to localize better via bilateral cochlear implants
      than their congenitally deaf peers.

PMID- 30299344
TI  - Effects of induction of labor prior to post-term in low-risk pregnancies: a
      systematic review.
AB  - OBJECTIVE: The objective of this review was to identify, assess and synthesize
      the best available evidence on the effects of induction prior to post-term on the
      mother and fetus. Maternal and fetal outcomes after routine labor induction in
      low-risk pregnancies at 41+0 to 41+6 gestational weeks (prior to post-term) were
      compared to routine labor induction at 42+0 to 42+6 gestational weeks (post
      term). INTRODUCTION: Induction of labor when a pregnancy exceeds 14 days past the
      estimated due date has long been used as an intervention to prevent adverse fetal
      and maternal outcomes. Over the last decade, clinical procedures have changed in
      many countries towards an earlier time for induction. A shift towards earlier
      inductions may lead to 15-20% more inductions. Given the fact that induction as
      an intervention can cause harm to both mother and child, it is essential to
      ensure that the benefits of the change in clinical practice outweigh the harms.
      INCLUSION CRITERIA: This review included studies with participants with expected
      low-risk deliveries, where both fetus and mother were considered healthy at
      inclusion and with no known risks besides the potential risk of the ongoing
      pregnancy. Included studies evaluated induction at 41+1-6 gestational weeks
      compared to 42+1-6 gestational weeks. Randomized control trials (RCTs) (n = 2),
      quasi-experimental trials (n = 2), and cohort studies (n = 3) were included. The
      primary outcomes of interest were cesarean section, instrumental vaginal
      delivery, low Apgar score (<= 7/5 min.), and low pH (< 7.10). Secondary outcomes
      included additional indicators of fetal or maternal wellbeing related to
      prolonged pregnancy or induction. METHODS: The following information sources were
      searched for published and unpublished studies: PubMed, CINAHL, Embase, Scopus,
      Swemed+, POPLINE; Cochrane, TRIP; Current Controlled Trials; Web of Science, and,
      for gray literature: MedNar; Google Scholar, ProQuest Nursing & Allied Health
      Source, and guidelines from Royal College of Obstetricians and Gynaecologists and
      The American College of Obstetricians and Gynecologists, according to the
      published protocol. In addition, OpenGrey and guidelines from National Institute
      for Health and Care Excellence, The World Health Organization, and The Society of
      Obstetricians and Gynaecologists of Canada were sought. Included papers were
      assessed by all three reviewers independently using the Joanna Briggs Institute
      System for the Unified Management, Assessment and Review of Information (JBI
      SUMARI). The standardized data extraction tool from JBI SUMARI was used. Data
      were pooled in a statistical meta-analysis model using RevMan 5, when the
      criteria for meta-analysis were met. Non-pooled results were presented
      separately. RESULTS: Induction at 41+0-6 gestational weeks compared to 42+0-6
      gestational weeks was found to be associated with an increased risk of overall
      cesarean section (relative risk [RR] = 1.11, 95% confidence interval [CI] 1.09
      1.14), cesarean section due to failure to progress (RR = 1.43, 95% CI 1.01-2.01),
      chorioamnionitis (RR = 1.13, 95% CI 1.05-1.21), labor dystocia (RR = 1.29, 95% CI
      1.22-1.37), precipitate labor (RR = 2.75, 95% CI 1.45-5.2), uterine rupture (RR =
      1.97, 95% CI 1.54-2.52), pH < 7.10 (RR = 1.9, 95% CI 1.48-2.43), and a decreased
      risk of oligohydramnios (RR = 0.4, 95% CI 0.24-0.67) and meconium stained
      amniotic fluid (RR = 0.82, 95% CI 0.75-0.91). Data lacked statistical power to
      draw conclusions on perinatal death. No differences were seen for postpartum
      hemorrhage, shoulder dystocia, meconium aspiration, 5-minute Apgar score < 7, or
      admission to neonatal intensive care unit. A policy of awaiting spontaneous onset
      of labor until 42+0-6 gestational weeks showed, that approximately 70% went into
      spontaneous labor. CONCLUSIONS: Induction prior to post-term was associated with
      few beneficial outcomes and several adverse outcomes. This draws attention to
      possible iatrogenic effects affecting large numbers of low-risk women in
      contemporary maternity care. According to The World Health Organization, expected
      benefits from a medical intervention must outweigh potential harms. Hence, our
      results do not support the widespread use of routine induction prior to post-term
      (41+0-6 gestational weeks).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- 30299345
TI  - Student and Faculty Experiences in the Flipped Learning Environment in
      Undergraduate Nursing.
AB  - AIM: The aim of the study was to describe student and faculty experiences in the
      flipped learning environment. BACKGROUND: Studies of flipped instruction in
      science, technology, engineering, and mathematics reveal improvements in student
      performance. There is limited research related to student and faculty experiences
      in the learning environment. METHOD: This study utilized a multiple-case study
      research design with two undergraduate nursing courses at two institutions.
      RESULTS: Student participants in Case A felt the implementation of flipped
      learning reflected the pillars of flipped learning more than Case B participants.
      The strategies used to implement flipped learning in the two cases were different
      as were student experiences. CONCLUSION: Three conclusions resulted from the
      study: flipped learning results in a shift in the student role that requires
      additional instructor support, instructors would benefit from guidance in the
      form of best practices, and nurse educators can use flipped learning to better
      meet the learning needs of their students.

PMID- 30299346
TI  - Impact of an HIV Care Coordination Program on Durable Viral Suppression.
AB  - BACKGROUND: To assess long-term effectiveness of an intensive and comprehensive
      Ryan White Part A-funded HIV Care Coordination Program (CCP) recruiting people
      living with HIV (PLWH) with a history of suboptimal HIV care outcomes. METHODS:
      We merged programmatic data on CCP clients with surveillance data on all adults
      diagnosed with HIV. Using propensity score matching, we identified a
      contemporaneous, non-CCP exposed comparison group. Durable viral suppression
      (DVS) was defined as regular VL monitoring and all VLs <=200 copies/mL in months
      13-36 of follow-up. RESULTS: Ninety percent of the combined cohort (N=12,414) had
      >=1 VL<=200 during the follow-up period (December 1, 2009 to March 31, 2016), and
      nearly all had routine VL monitoring, but only 36.8% had DVS. While DVS did not
      differ overall (relative risk[RR]: 0.99, 95%CI: 0.95-1.03), CCP clients without
      any VL suppression in the 12 months pre-enrollment showed higher DVS versus
      'usual care' recipients (21.3% versus 18.4%; RR: 1.16, 95%CI: 1.04-1.29).
      CONCLUSIONS: Enrollment in an intensive intervention modestly improved DVS among
      those unsuppressed prior to CCP enrollment. This program shows promise for
      meeting treatment-as-prevention goals and advancing progress along the HIV care
      continuum, if people without evidence of VLS are prioritized for CCP enrollment
      over those with recent evidence of VLS. Low overall DVS (<40%) levels underscore
      a need for focused adherence-maintenance interventions, in a context of high
      treatment access.

PMID- 30299348
TI  - Burkitt Lymphoma Presenting With Intracardiac Mass and Tumor Thrombosis in the
      Anterior Mediastinum With Literature Review.
AB  - Burkitt lymphoma manifesting as an intracardiac mass is a rare entity. This
      report describes the case of a 10-year-old boy who presented with an intracardiac
      mass and tumor thrombosis in the anterior mediastinum that proved to be Burkitt
      lymphoma. The LMB-96 chemotherapy protocol was given and at the end of the
      treatment there was still residual mass. A biopsy was performed and the pathology
      revealed thymus tissue. The patient has been in complete remission for 3 months.
      Burkitt lymphoma has a short doubling time and an intracardiac lesion can become
      life threatening. Early recognition and prompt treatment are crucial in achieving
      optimal outcomes.

PMID- 30299347
TI  - The Association of Fibroblast Growth Factor-23 (FGF-23) with Incident Frailty in
      HIV-Infected and -Uninfected Individuals.
AB  - BACKGROUND: In the Multicenter AIDS Cohort Study, we examined whether fibroblast
      growth factor-23 (FGF-23), a bone-derived phosphaturic hormone involved in bone
      metabolism, is associated with incident frailty. Further, we examined whether
      this association differs by HIV serostatus and race. METHODS: Of 715 men assessed
      for frailty and selected for FGF-23 measurements using stored blood samples (2007
      2011), 512 men were non-frail at/prior to the baseline visit. Frailty was defined
      by the presence of >=3 of the following on two consecutive 6-month visits within
      1 year: unintentional weight loss >=10 pounds, weakness, slowness, low energy and
      low physical activity. We determined the association of FGF-23 levels with
      incident frailty using proportional hazards models adjusting for
      sociodemographics, co-morbidities and kidney function. RESULTS: Sixty-five
      percent were HIV-infected; 29% were black. Median baseline FGF-23 levels were
      lower in HIV-infected versus HIV-uninfected men (33.7 vs. 39.9 rU/mL, p=0.006)
      but similar by race. During a median follow-up of 6.6 years, 32 men developed
      frailty; they had higher baseline FGF-23 levels versus men who remained non-frail
      (45 vs. 36 rU/mL, p=0.02). FGF-23 (per doubling) was associated with a 1.63-fold
      risk of frailty (95%CI:1.19, 2.23); results did not differ by HIV serostatus.
      Conversely, FGF-23 was associated with a 2.72-fold risk of frailty among blacks
      (95%CI:1.51, 4.91) but had minimal association among non-blacks (HR=1.26,
      95%CI:0.77, 2.05; p-interaction=0.024). CONCLUSION: Among men with or at-risk for
      HIV infection, higher FGF-23 was associated with greater risk of frailty,
      particularly in blacks. The mechanisms by which FGF-23 may contribute to frailty
      warrant further study.

PMID- 30299349
TI  - Not All Pediatric Bladder Masses are Rhabdomyosarcoma: Report of a Rare Case With
      Review of the Literature.
AB  - Leiomyoma of the urinary bladder in the pediatric age group is one of the rarest
      tumors with only 2 case reports in the English literature. Rhabdomyosarcoma is
      the commonest tumor at this site in this age group. It needs to be distinguished
      from rhabdomyosarcoma by histomorphology for appropriate treatment and
      management. We report the third case of urinary bladder leiomyoma arising in a 6
      year-old boy with a short review of the literature.

PMID- 30299351
TI  - Successful Treatment of an Adolescent Male With Severe Refractory Evans Syndrome
      Using Bortezomib-based Therapy.
AB  - Evans syndrome is defined by bilineal autoimmune cytopenia, typically coombs
      positive hemolytic anemia and thrombocytopenia. Corticosteroids are the mainstay
      of treatment, with rituximab and/or mycophenolate mofetil often used in steroid
      refractory cases. However, no treatment methodology has ever evaluated by a
      randomized clinical trial. We present a 15-year-old boy with Evans syndrome and
      common variable immunodeficiency who experienced a severe, refractory flare 16
      months postsplenectomy. After failing to respond to multiple other agents, he
      achieved a durable response to a bortezomib-based regimen. Bortezomib may be a
      reasonable second or third line option, especially before high-morbidity
      therapies such as splenectomy or stem cell transplantation.

PMID- 30299350
TI  - Gray Zone Lymphoma Arising in the Neck of a Teenager With a Germline Mutation in
      TP53.
AB  - Gray zone lymphoma is an aggressive disease for which appropriate management is
      still debated. We report a 15-year-old girl with a cervical mass, an enlarged
      ipsilateral tonsil, and anemia. Both sites showed hypermetabolism on F18-FG
      positron emission tomography/CT. Surgical resection was diagnostic of Epstein
      Barr virus-negative gray zone lymphoma cervical and tonsillar involvement. No
      abnormality was found in cytogenetic analysis on tumor cells. However, exome
      sequencing in peripheral blood DNA revealed a germline mutation in TP53. Complete
      response was achieved after surgery and 6 cycles of rituximab with dose-adjusted
      etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin regimen.

PMID- 30299352
TI  - Use of Tranexamic Acid in an Uncommon Triad: Hemorrhagic Stroke, Sickle Cell
      Disease and Severe Coagulopathy.

PMID- 30299353
TI  - Multidrug-resistant Gram-negative infection in solid organ transplant recipients:
      implications for outcome and treatment.
AB  - PURPOSE OF REVIEW: Solid organ transplantation (SOT) is the best therapeutic
      option for both acute and chronic end-stage diseases. The development of more
      potent and safer immunosuppressants and the improvement of prophylactic practices
      have significantly diminished the morbidity and mortality associated with
      rejection and opportunistic infections. However, infections produced by multidrug
      resistant (MDR) Gram-negative bacilli (GNB) have recently emerged as a
      significant threat. RECENT FINDINGS: The Spanish Society of Transplantation
      (SET), the Group for Study of Infection in Transplantation of the Spanish Society
      of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC) and the Spanish
      Network for Research in Infectious Diseases (REIPI) have recently published their
      recommendations concerning the management of MDR GNB infections in SOT
      recipients. We review this guideline, and also the most recent available
      evidence, focusing on donor-derived infections, colonized recipients and
      therapeutic approaches. SUMMARY: Overall, donor and recipient colonization is
      associated with an increased risk of infection by MDR GNB, although none of these
      circumstances constitutes an absolute contraindication to transplantation. SOT
      recipients with risk factors for MDR GNB infection should receive an empirical
      treatment which includes potentially active antibiotics. Targeted therapy should
      be adjusted according to antimicrobial susceptibility testing and severity of
      infection.

PMID- 30299354
TI  - How to optimize antibiotic pharmacokinetic/pharmacodynamics for Gram-negative
      infections in critically ill patients.
AB  - PURPOSE OF REVIEW: Optimized antibiotic dosing regimens improve survival rates in
      critically ill patients. However, dose optimization is challenging because of
      fluctuating antibiotic pharmacokinetics both between patients and within a single
      patient. This study reviews the pharmacokinetic changes that occur in critically
      ill patients, along with the pharmacodynamics and toxicodynamics of antibiotics
      commonly used for the treatment of Gram-negative bacterial infections to
      formulate a recommendation for antibiotic dosing at the bedside. RECENT FINDINGS:
      Recent studies highlight that critically ill patients do not achieve therapeutic
      antibiotic exposures with standard antibiotic dosing. Although dose increases are
      required, the method of administration, such as the use of beta-lactam antibiotic
      continuous infusions and nebulized aminoglycoside administration, may improve
      efficacy and limit toxicity. In addition, the increased availability of
      therapeutic drug monitoring and antibiotic dosing software allow the formulation
      of individualized dosing regimens at the bedside. SUMMARY: When prescribing
      antibiotic doses, the clinician should consider antibiotic pharmacokinetic and
      pharmacodynamic principles. Before initiating high-dose antibiotic therapy,
      therapeutic drug monitoring may be considered to assist the clinician to optimize
      antibiotic treatment and minimize potential toxicity.

PMID- 30299355
TI  - Hepatitis B virus and hepatitis C virus infection in immunocompromised patients.
AB  - PURPOSE OF REVIEW: To provide an update on recent studies of hepatitis B virus
      (HBV) and hepatitis C virus (HCV) infections in cancer patients with an emphasis
      on viral reactivation after cancer treatment, new antiviral therapies, and safety
      concerns. RECENT FINDINGS: The diagnostic criteria for HBV reactivation in
      patients receiving cancer therapy were revised in 2018. HBV reactivation in these
      patients is preventable, even with the use of new cancer therapies. HCV
      reactivation also has been reported in cancer patients, particularly those with
      hematologic malignancies, and is not a virologic condition usually associated
      with poor outcome. Prophylaxis to prevent HCV reactivation is not recommended
      because therapy with direct-acting antivirals eradicates the infection in the
      majority of cancer patients. SUMMARY: Cancer patients with HBV or HCV infection
      are at risk for viral reactivation, with many similarities between these two
      infections. Patients at high risk for reactivation will benefit significantly
      from taking oral antivirals, which will reduce the risk of HBV reactivation or
      prevent development of HCV reactivation following its virologic cure.

PMID- 30299356
TI  - Neuraminidase inhibitor resistance in influenza: a clinical perspective.
AB  - PURPOSE OF REVIEW: Neuraminidase inhibitors (NAIs), including oseltamivir,
      zanamivir, and peramivir, is the main class of antiviral available for clinical
      use. As such, development of resistance toward these agents is of great clinical
      and public health concern. RECENT FINDINGS: At present, NAI resistance remains
      uncommon among the circulating viruses (oseltamivir <3.5%, zanamivir <1%).
      Resistance risk is slightly higher in A(H1N1) than A(H3N2) and B viruses.
      Resistance may emerge during drug exposure, particularly among young children (<5
      years), the immunocompromised, and individuals receiving prophylactic regimens.
      H275Y A(H1N1) variant, showing high-level oseltamivir resistance, is capable of
      causing outbreaks. R294K A(H7N9) variant shows reduced inhibition across NAIs.
      Multi-NAI resistance has been reported in the immunocompromised. SUMMARY: These
      findings highlight the importance of continuous surveillance, and assessment of
      viral fitness and transmissibility of resistant virus strains. Detection can be
      challenging, especially in a mix of resistant and wild-type viruses. Recent
      advances in molecular techniques (e.g. targeted mutation PCR, iART, ddPCR,
      pyrosequencing, next-generation sequencing) have improved detection and our
      understanding of viral dynamics. Treatment options available for oseltamivir
      resistant viruses are limited, and susceptibility testing of other NAIs may be
      required, but non-NAI antivirals (e.g. polymerase inhibitors) that are active
      against these resistant viruses are in late-stage clinical development.

PMID- 30299357
TI  - Combination versus monotherapy for the treatment of infections due to carbapenem
      resistant Enterobacteriaceae.
AB  - PURPOSE OF REVIEW: Combination therapy is a common strategy for treatment of
      multidrug resistant infections. Despite the strong twin rationales of improving
      efficacy and reducing resistance development, the evidence supporting this
      strategy remains controversial. The aims of this review are to assess the most
      recent studies supporting the use of combination therapy for treating infections
      because of carbapenem-resistant Enterobacteriaceae (CRE) and to highlight
      relevant areas for further research. RECENT FINDINGS: Evidence supporting the use
      of combination therapy for the treatment of CRE remains limited to in-vitro
      experiments and observational studies with considerable risk of bias. Very few
      antibiotic combinations have been tested in well designed randomized controlled
      trials, making it difficult to draw general conclusions for clinical practice.
      SUMMARY: Further studies are urgently needed to test the most promising
      synergistic combinations. New drugs potentially active against CRE should also to
      be tested in studies with adequate sample size and truly representative of the
      general patient population.

PMID- 30299358
TI  - Current management of Gram-negative septic shock.
AB  - PURPOSE OF REVIEW: Sepsis is a common condition in critically ill patients and
      associated with high morbidity and mortality. Sepsis is the result of infection
      by many potential pathogens, including Gram-negative bacteria. There are no
      specific antisepsis therapies and management relies largely on infection control
      and organ support, including hemodynamic stabilization. We discuss these key
      aspects and briefly mention potential immunomodulatory strategies. RECENT
      FINDINGS: New aspects of sepsis management include the realization that early
      treatment is important and that fluids and vasopressor agents should be
      administered simultaneously to insure rapid restoration of an adequate perfusion
      pressure to limit development and worsening of organ dysfunction. New
      immunomodulatory therapies, both suppressive and stimulatory, are being tested.
      SUMMARY: Early diagnosis enabling rapid treatment can optimize outcomes. The
      multiple components of adequate sepsis management necessitate a team approach.

PMID- 30299359
TI  - The ideal patient profile for new beta-lactam/beta-lactamase inhibitors.
AB  - PURPOSE OF REVIEW: The worldwide spread of extended-spectrum beta-lactamase
      (ESBL)-producing bacteria, the overuse of carbapenems, the emergence of
      carbapenemase-producing organisms and the growing importance of multidrug
      resistant and/or extended drug-resistant strains have totally changed
      prescribers' habits, leading to very few treatment options in many cases. Beta
      lactam/beta-lactamase inhibitor (BLBLI) combinations should be considered as an
      alternative to carbapenems for treating ESBL-producing bacteria and Pseudomonas
      aeruginosa infections. The purpose of this study was to provide insight
      concerning the patients who would constitute ideal candidates to receive these
      new BLBLI combinations. RECENT FINDINGS: Ceftolozane/tazobactam and
      ceftazidime/avibactam are the first drugs constituting the use of new beta
      lactamase inhibitors. Ceftolozane/tazobactam is the drug of choice for treating
      MDR/XDR P. aeruginosa infections. Ceftazidime/avibactam is the best drug
      available for treating KPC and OXA-48 carbapenemase-producing Enterobacteriaceae.
      Ceftolozane/tazobactam and ceftazidime/avibactam are both carbapenem-sparing
      agents for treating ESBL-producing Enterobacteriaceae. The role of
      carbapenem/inhibitors remains to be clarified. SUMMARY: Each BLBLI combination
      has distinctive specificities and limitations that need to be investigated
      cautiously. Randomized trials will play a key role in defining the best
      strategies. Infection control measures and prompt diagnosis remain fundamental to
      prevent dissemination of MDR pathogens in healthcare settings and to optimize
      early antimicrobial treatment.

PMID- 30299360
TI  - Polyclonal and monoclonal antibodies for the treatment of influenza.
AB  - PURPOSE OF REVIEW: This review summarizes past and ongoing efforts for using
      polyclonal and monoclonal antibodies for the treatment of influenza, and is
      focused on products that have entered clinical trials. RECENT FINDINGS: At least
      three polyclonal and eight monoclonal antibody products have been tested in
      clinical trials for the treatment of influenza. Considered across the two classes
      of therapeutics, these products appear to be safe and well tolerated. However,
      the efficacy results have been mixed and inconclusive. To date, no products have
      consistently shown superiority to currently available antivirals. SUMMARY: No
      products within these two classes have been licensed, and several products appear
      to have stopped further clinical development. There are several ongoing studies
      that are anticipated to be completed or reported in the next 1-2 years which will
      be critical for understanding the value of polyclonal and monoclonal antibodies
      in the treatment of influenza.

PMID- 30299361
TI  - Invasive fungal disease and cytomegalovirus infection: is there an association?
AB  - PURPOSE OF REVIEW: Invasive fungal disease (IFD) and cytomegalovirus (CMV)
      infections occur frequently, either concomitantly or sequentially in immune
      compromised hosts. Although there is extensive knowledge of the risk factors for
      these infections as single entities, the inter-relationship between opportunistic
      fungii and CMV has not been comprehensively explored. RECENT FINDINGS: Both solid
      organ and stem cell transplant recipients who develop CMV invasive organ disease
      are at an increased risk of developing IFD, particularly aspergillosis and
      Pneumocystis pneumonia (PCP). Moreover, CMV viremia and recipient CMV serostatus
      also increased the risk of both early and late-onset IFD. Treatment-related
      factors, such as ganciclovir-induced neutropenia and host genetic Toll-like
      receptor (TLR) polymorphisms are likely to be contributory. Less is known about
      the relationship between CMV and IFD outside transplantation, such as in patients
      with hematological cancers or other chronic immunosuppressive conditions.
      Finally, few studies report on the relationship between CMV-specific treatments
      or the viral/antigen kinetics and its influence on IFD management. SUMMARY: CMV
      infection is associated with increased risk of IFD in posttransplant recipients
      because of a number of overlapping and virus-specific risk factors. Better
      understanding of how CMV virus, its related treatment, CMV-induced
      immunosuppression and host genetic factors impact on IFD is warranted.

PMID- 30299362
TI  - Antifungal stewardship: developments in the field.
AB  - PURPOSE OF REVIEW: To outline key drivers and components of antifungal
      stewardship (AFS) programmes, the evidence for specific interventions, and
      methods to assess performance of programmes. RECENT FINDINGS: Recent developments
      in antifungal resistance and breakthrough invasive fungal diseases have increased
      the urgency for effective AFS. In practice, however, few hospitals have dedicated
      AFS programmes. To date, AFS programmes have centred around the provision of
      expert bedside reviews and have reduced costs and consumption of antifungal
      agents. Incorporating tools such as fungal diagnostics and therapeutic drug
      monitoring into AFS programme models is recommended. However, the application and
      impact of these tools in this context have not been adequately assessed. The
      effectiveness of AFS programmes has been measured in multiple ways but a
      standardized method of evaluation remains elusive. Few studies have explored the
      impact of AFS interventions on patient outcomes. SUMMARY: The uptake of formal
      AFS programmes has been slow. New initiatives integrating AFS tools in
      programmes, and measuring the impacts on patient outcomes are required given such
      data are not readily available. A comprehensive approach to evaluate AFS
      programmes by correlating the quantity and quality of antifungal prescribing with
      impacts on patient outcomes is needed. Consensus definitions for core AFS metrics
      are required to benchmark performance and are essential to the resourcing and
      sustainability of these programmes.

PMID- 30299363
TI  - Whipple's disease and Tropheryma whipplei infections: when to suspect them and
      how to diagnose and treat them.
AB  - PURPOSE OF REVIEW: The delay between first clinical signs and diagnosis of
      Whipple's disease and Tropheryma whipplei infections is more than 6 years, and
      relapses are frequently observed, resulting in a need for clinicians to be aware
      of this infection. RECENT FINDINGS: 18 FDG-PET is useful in the diagnosis and the
      follow-up of patients (particularly in case of neurological involvement).
      Histological involvement remains the goldstandard for classic Whipple's disease
      diagnosis. PCR performed on biopsies of fluid is the main tool for the diagnosis
      of localized chronic infections. PCR performed on urine samples should become an
      important role of noninvasive diagnostic strategies, while T. whipplei PCR
      performed on saliva and stool lack specificity. Because of lifetime
      susceptibility to T. whipplei and in-vitro susceptibility data, a 1-year course
      of doxycycline and hydroxychloroquine followed by a lifelong treatment by
      doxycycline is recommended for Whipple's disease, localized endocarditis and
      encephalitis. SUMMARY: Clinical involvement of the different T. whipplei
      infections is well described, as well as the treatment of Whipple's disease,
      endocarditis and encephalitis. The place of PCR performed on urine remains to be
      clarified for diagnosis of localized T. whipplei infections and acute infections
      as well as the optimal treatment for arthritis and acute infections.

PMID- 30299364
TI  - Rational approach in the management of Pseudomonas aeruginosa infections.
AB  - PURPOSE OF REVIEW: This review details the management of Pseudomonas aeruginosa
      infections covering both current and future treatment options that are and may be
      available for the clinicians. RECENT FINDINGS: Pseudomonas aeruginosa infections
      are a great concern in hospital-acquired infections with very limited therapeutic
      options. The increasing antibiotic resistance has led to a need for different
      treatment choices that range from the use of new antibiotics to new nonantibiotic
      alternative agents to kill or disarm the pathogen. SUMMARY: New molecules such as
      ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam have shown
      an adequate activity against P. aeruginosa, especially against multidrug
      resistance strains. Other nonantibiotic alternative treatments, such as
      antibodies, bacteriocins or phage therapy, have shown promising results, but
      future clinical studies are needed.

PMID- 30299366
TI  - Update on epidemiology and appropriate treatment of life-threatening gram
      negative infections.

PMID- 30299367
TI  - Invasive pulmonary aspergillosis complicating severe influenza: epidemiology,
      diagnosis and treatment.
AB  - PURPOSE OF REVIEW: Bacterial super-infection of critically ill influenza patients
      is well known, but in recent years, more and more reports describe invasive
      aspergillosis as a frequent complication as well. This review summarizes the
      available literature on the association of invasive pulmonary aspergillosis (IPA)
      with severe influenza [influenza-associated aspergillosis (IAA)], including
      epidemiology, diagnostic approaches and treatment options. RECENT FINDINGS:
      Though IPA typically develops in immunodeficient patients, non-classically
      immunocompromised patients such as critically ill influenza patients are at high
      risk for IPA as well. The morbidity and mortality of IPA in these patients is
      high, and in the majority of them, the onset occurs early after ICU admission. At
      present, standard of care (SOC) consists of close follow-up of these critically
      ill influenza patients with high diagnostic awareness for IPA. As soon as there
      is clinical, mycological or radiological suspicion for IAA, antifungal azole
      based therapy (e.g. voriconazole) is initiated, in combination with therapeutic
      drug monitoring (TDM). Antifungal treatment regimens should reflect local
      epidemiology of azole-resistant Aspergillus species and should be adjusted to
      clinical evolution. TDM is necessary as azoles like voriconazole are
      characterized by nonlinear pharmacokinetics, especially in critically ill
      patients. SUMMARY: In light of the frequency, morbidity and mortality associated
      with influenza-associated aspergillosis in the ICU, a high awareness of the
      diagnosis and prompt initiation of antifungal therapy is required. Further
      studies are needed to evaluate the incidence of IAA in a prospective multicentric
      manner, to elucidate contributing host-derived factors to the pathogenesis of
      this super-infection, to further delineate the population at risk, and to
      identify the preferred diagnostic and management strategy, and also the role of
      prophylaxis.

PMID- 30299368
TI  - "Progress in Corneal Research and Practice in Japan and Abroad": The 23rd Annual
      Meeting of the Kyoto Cornea Club, November 24 and 25, 2017.

PMID- 30299369
TI  - Fuchs Endothelial Corneal Dystrophy Through the Prism of Oxidative Stress.
AB  - The corneal endothelium (CE) is vital for maintaining the water balance and
      clarity of the cornea. The CE is a cell layer that is particularly susceptible to
      aging because of its postmitotic arrest, high metabolic activity involving
      pumping of ions, and lifelong exposure to ultraviolet light. Despite gradual age
      related cell loss, a sufficient number of CE cells are preserved during the
      lifespan of an individual. However, in conditions such as Fuchs endothelial
      corneal dystrophy (FECD), permanent loss of CE cells leads to corneal edema and
      loss of vision requiring corneal transplantation. FECD is a genetic and oxidative
      stress disorder manifested by abnormal cell-matrix interactions and expedited
      cellular aging culminating in cellular death. Because the endothelium has minimal
      replicative capacity in vivo and an inability to replace its genome, it is
      particularly prone to cumulative DNA damage acquired throughout life. In FECD,
      the underlying genetic defects make the CE genome even more vulnerable to this
      damage, to the point of causing mitochondrial dysfunction, mitochondrial membrane
      potential loss, and excessive mitophagy activation. Endogenous and exogenous
      intracellular stressors alter the synthetic footprint of CE cells, leading to
      endothelial-mesenchymal transition and secretion of aberrant extracellular matrix
      (in the form of guttae), resembling scar formation in other organs. In turn, the
      guttae or endothelial scars contribute to a vicious cycle of FECD pathogenesis
      and, by further inducing endothelial-mesenchymal transition and oxidant
      antioxidant imbalance, perpetuate the molecular changes of the degenerating
      endothelium.

PMID- 30299370
TI  - Preganglionic Parasympathetic Denervation Rabbit Model for Innervation Studies.
AB  - PURPOSE: Tear secretion from the main lacrimal gland (LG) is mainly regulated by
      parasympathetic nerves. We performed several innervation studies to investigate
      lacrimation. METHODS: In male rabbits, we performed a retrograde dye-tracing
      study of LG innervation, evaluated preganglionic parasympathetic denervation, and
      administered glial cell-derived neurotrophic factor (GDNF) in the surgical area
      after parasympathetic denervation. RESULTS: Accumulation of fluorescent dye was
      observed in the pterygopalatine ganglion cells on the same side as the dye
      injection into the main LG. Fewer stained cells were observed in the cervical and
      trigeminal ganglia. After parasympathetic denervation surgery, tear secretion was
      decreased, and fluorescein and rose bengal staining scores were increased at day
      1 after surgery and remained increased for 3 months on the denervated side only.
      Most of the effects in rabbits with parasympathetic denervation were not
      recovered by administration of GDNF. CONCLUSIONS: The main LG is primarily
      innervated by parasympathetic nerves to stimulate tear secretion. After
      preganglionic parasympathetic denervation, lacrimation was decreased, resulting
      in dry eyes, and this was maintained for at least 3 months. Administration of
      GDNF only minimally altered the effects of denervation.

PMID- 30299372
TI  - Simulating Cultural Competence.

PMID- 30299371
TI  - Detection of IDH1 and IDH2 Mutation in Formalin-fixed Paraffin-embedded Gliomas
      Using Allele-specific COLD-PCR and Probe Melting Curve Analysis.
AB  - Many tumors, especially gliomas, contain an isocitrate dehydrogenase (IDH)
      mutation that can be used for clinical diagnosis and prognosis. Our study aimed
      to develop a new reliable detection assay for IDH1 and IDH2 mutations for
      clinical diagnosis based on the allele-specific (AS) coamplification with lower
      denaturing-polymerase chain reaction (COLD-PCR) and probe melting curve analysis
      (PMCA). The method includes 3 elements allowing for the sensitive detection of
      low-abundance mutations: (1) PCR amplification of the target fragments with AS
      primers; (2) COLD-PCR; and (3) PMCA for differentiating the different mutations
      after amplification. We conducted a blinded study with 45 paraffin-embedded
      gliomas specimens and 13 fresh specimens screened for IDH mutations using Sanger
      sequencing. Concordance between the results of our AS-COLD-PCR/PMCA assay and
      Sanger sequencing was 100%. Our assay appeared to be superior to direct
      sequencing with a much higher sensitivity of 0.4% mutations. In summary, our
      assay is a cost-effective, convenient, and sensitive method for detecting IDH
      mutations and could be applied in the clinical setting to assess small brain
      biopsies.

PMID- 30299373
TI  - An Innovative Audiovisual Reflective Portfolio for Nursing Students.

PMID- 30299374
TI  - Perfusion of Porcine Kidneys with Macromolecular Heparin Reduces Early Ischemia
      Reperfusion Injury.
AB  - BACKGROUND: Previously we have been able to demonstrate the possibility of
      coating the inner surface of the renal arteries in porcine kidneys with a heparin
      conjugate during hypothermic machine perfusion (HMP). The purpose of this study
      was to assess the efficacy of this treatment in reducing early ischemia
      reperfusion injury. METHOD: Brain death was induced in male landrace pigs by
      stepwise volume expansion of an epidural balloon catheter until negative cerebral
      perfusion pressure was obtained. Both kidneys (matched pairs; n=6+6) were
      preserved for 20 hours by HMP during which 50 mg heparin conjugate was added to 1
      of the HMP systems (treated group). A customized ex vivo normothermic oxygenated
      perfusion (NP) system with added exogenous creatinine was used to evaluate early
      kidney function. Blood, urine and histological samples were collected during the
      subsequent 3 hours of NP. RESULTS: Kidney weight was lower at the end of NP
      (p=0.017) in the treated group compared to control kidneys. The rate of decline
      in creatinine level was faster (p=0.024), total urinary volume was higher
      (p=0.031) and the level of urine neutrophil gelatinase-associated lipocalin
      (NGAL) was lower (p=0.031) in the treated group. Histologically, less tubular
      changes were seen (p=0.046). During NP intrarenal resistance remained lower
      (p<0.0001) in the treated group. CONCLUSIONS: Perfusion of porcine kidneys with
      heparin conjugate during HMP reduces preservation injury and improves organ
      function shortly after reperfusion. No increased risk of bleeding was seen in
      this setup. This protective strategy may potentially improve the quality of
      transplanted kidneys in the clinical setting.

PMID- 30299376
TI  - Words matter.

PMID- 30299375
TI  - Do we need noninvasive biomarkers for delayed graft function after kidney
      transplantation?

PMID- 30299377
TI  - Suicide risk assessment and prevention.

PMID- 30299378
TI  - Delay in Hip Fracture Surgery Prolongs Postoperative Hospital Length of Stay but
      Does Not Adversely Affect Outcomes at 30 Days.
AB  - OBJECTIVES: To evaluate the association between the timing of hip fracture
      surgery with postoperative length of stay and outcomes. DESIGN: Retrospective
      review using the American College of Surgeons National Surgical Quality
      Improvement Program database. SETTING: National inquiry database incorporating
      140 academic and private medical centers. PATIENTS: Seventeen thousand four
      hundred fifty-nine patients who underwent surgery for a hip fracture between 2006
      and 2013 were identified from the National Surgical Quality Improvement Program
      database. INTERVENTION: Surgical management of hip fractures was performed at the
      discretion of participating surgeons. OUTCOME MEASURE: Thirty-day outcomes
      including postoperative length of stay, readmission rates, reoperation rates,
      complications, and mortality rates. RESULTS: Of the 17,459 patients, 4107 (23.5%)
      were operated on within 24 hours, 8740 (50.1%) within 24-48 hours, and 4612
      (26.4%) more than 48 hours after hospital admission. Increased time to surgery
      was associated with longer postoperative hospital length of stay. Prolonged time
      to surgery did not adversely affect postoperative outcomes. CONCLUSIONS: Although
      a delay in the management of hip fractures is associated with an increase in
      postoperative hospital length of stay, 30-day postoperative outcomes are not
      adversely affected in patients undergoing hip fracture fixation. LEVEL OF
      EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 30299379
TI  - Intraoperative Cone Beam Tomography and Navigation for Displaced Acetabular
      Fractures: A Comparative Study.
AB  - OBJECTIVES: To evaluate the accuracy of reduction of the acetabular articular
      surface using an intraoperative computed tomography scanner (O-Arm) and screw
      navigation compared with a classical open technique. DESIGN: Prospective matched
      cohort study. SETTING: Tertiary referral center. PATIENTS/PARTICIPANTS: Adult
      patients with acute acetabular fractures were included in the study. All patients
      were treated by 2 senior surgeons using intraoperative imaging and screw
      navigation. MAIN OUTCOME MEASUREMENTS: The primary outcome measure was articular
      reduction. Secondary outcomes were radiation dosage, operative variables
      [operative time, time for image acquisition, intraoperative bleeding (cell
      saver), number of surgical plates, and number of screws], and postoperative
      variables (first postoperative day pain on the visual analog scale, postoperative
      transfusion, and hemoglobin change). P < 0.05 was considered statistically
      significant. RESULTS: Thirty-five patients were treated in the inclusion period
      (2016-2017) and were matched to 35 cases in our database (2013-2016). Mean age
      was 43 years, and the most common fracture type was a both-column fracture
      (OTA/AO type C). Postoperative image analysis showed that reduction was achieved
      in 87.1% of the cases in the O-Arm group versus 64.7% in the control group (P <
      0.05). Mean gap of the articular fragments was 3.6 mm in the O-Arm group compared
      with 5.6 mm (P = 0.01) in the control group. There was no significant difference
      between the 2 groups in regards to all other studied variables except a decrease
      in intraoperative blood loss and transfusions and an increase in surgical time
      with the O-Arm group. Finally, the total radiation dose was decreased using the
      intraoperative O-Arm compared with a routine postoperative computed tomography
      scan (dose length product in O-Arm: 498 mGy.cm; dose length product in historical
      group: 715 mGy.cm). CONCLUSIONS: Using intraoperative imaging and screw
      navigation for displaced acetabular fractures allow screw navigation with
      increasing articular surface reduction accuracy. Operative and anesthesia times
      were not increased, whereas radiation exposure to the patient was significantly
      decreased. We recommend the use of intraoperative imaging for the treatment of
      displaced acetabular fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30299380
TI  - Far Cortical Locking Fixation of Distal Femur Fractures is Dominated by Shear at
      Clinically Relevant Bridge Spans.
AB  - OBJECTIVES: Far cortical locking (FCL) constructs have been shown to increase
      axial interfragmentary displacement while limiting shear and have been
      specifically recommended in the treatment of distal femur fractures. However,
      there is no available data regarding their mechanical behavior within the range
      of bridge spans typically employed for comminuted distal femur fractures. This
      biomechanical study of distal femur locked plate fixation assessed four methods
      of diaphyseal fixation for associated axial and shear displacement at bridge
      spans typically employed in clinical practice. METHODS: Distal femur locking
      plates were used to bridge simulated fractures in femur surrogates with four
      different methods of diaphyseal fixation (bicortical locking, bicortical
      nonlocking, near cortical locking, and FCL). Axial and shear displacement were
      assessed at five different bridge spans for each fixation method. RESULTS:
      Diaphyseal fixation type was associated with the amount of shear (p = 0.04), but
      not the amount of axial displacement (p = 0.39). Specifically, FCL constructs
      demonstrated greater shear than bicortical locking (median 4.57 vs 2.94mm, p =
      0.02) and bicortical nonlocking (median 4.57 vs 3.41mm, p = 0.02) constructs.
      CONCLUSIONS: Unexpectedly, FCL constructs demonstrated greater shear than
      bicortical locking and nonlocking constructs and similar axial displacement for
      all fixation methods. Bridge span had a dominant effect on displacement that
      interacted negatively with more flexible FCL diaphyseal fixation. Potentially
      interactive construct features are best studied in concert. Given the complexity
      of these relationships, computational modeling will likely play an integral role
      in future mechanotransduction research.

PMID- 30299381
TI  - Ease of use of electronic health records and relational coordination among
      primary care team members.
AB  - BACKGROUND: Electronic health records (EHRs) have potential to improve quality,
      health outcomes, and efficiency, but little is known about the mechanisms through
      which these improvements occur. PURPOSE: One potential mechanism could be that
      EHRs improve care team communication and coordination, leading to better
      outcomes. To test this hypothesis, we examine whether ease of EHR use is
      associated with better relational coordination (RC), a measure of team
      communication and coordination, among primary care team members. METHODOLOGY:
      Surveys of adult primary care team members (n = 304) of 16 practices of two
      accountable care organizations in Chicago and Los Angeles were analyzed. The
      survey included a validated measure of RC and a measure of ease of EHR use from a
      national survey. Linear regression models estimated the association of ease of
      EHR use and RC, controlling for care site and patient demographics and accounting
      for cluster-robust standard errors. An interaction term tested a differential
      association of ease of EHR use and RC for primary care providers (PCPs) versus
      non-PCPs. RESULTS: Ease of EHR use (mean = 3.5, SD = 0.6, range: 0-4) and RC were
      high (mean = 4.0, SD = 0.7, range: 0-5) but differed by occupation. In regression
      analyses, a 1-point increase in ease of EHR use was associated with a 0.36 point
      higher RC score (p = .001). The association of ease of EHR and RC use was
      stronger for non-PCPs than PCPs. CONCLUSION: Ease of EHR use is associated with
      better RC among primary care team members, and the benefits accrue more to non
      PCPs than to PCPs. PRACTICE IMPLICATIONS: Ensuring that clinicians and staff
      experience EHRs as easy to use for accessing and integrating data and for
      communication may produce gains in efficiency and outcomes through high RC.
      Future studies should examine whether interventions to improve EHR usability can
      lead to improved RC and patient outcomes.

PMID- 30299382
TI  - Integration of cardiologists with hospitals: Effects on physician compensation
      and productivity.
AB  - BACKGROUND: Hospital-physician vertical integration involving employment of
      physicians has increased considerably over the last decade. Cardiologists are one
      group of specialists being increasingly employed by hospitals. Although hospital
      physician integration has the potential to produce economic and societal
      benefits, there is concern that this consolidation may reduce competition and
      concentrate bargaining power among providers. In addition, hospitals may be
      motivated to offer cardiologists higher compensation and reduced workloads as an
      incentive to integrate. PURPOSE: The aim of the study was to determine if there
      are differences in compensation and clinical productivity, measured by work
      relative value units (RVUs), for cardiologists as they transition from being
      independent practitioners to being employed by hospitals. METHODOLOGY/APPROACH:
      This study was a quantitative, retrospective, longitudinal analysis, comparing
      the compensation and work RVUs of integrated cardiologists to their compensation
      and work RVUs as independent cardiologists. Data from the MedAxiom Annual Survey
      from 2010 to 2014 were used. Participants included 4,830 unique cardiologists
      that provided 13,642 pooled physician-year observations, with ownership status,
      compensation, work (RVUs), and other characteristics as variables for analysis.
      RESULTS: Results from the multivariate regressions indicate that average
      compensation for cardiologists increases by $129,263.1 (p < .001) when they move
      from independent to integrated practice. At the same time, physician work RVUs
      decline by 398.04 (p = .01). CONCLUSION: Our findings support the conjecture that
      hospitals may be offering higher pay and lower workloads to incentivize
      cardiologists to integrate. PRACTICE IMPLICATIONS: Although hospitals may have
      goals of quality improvement and lower costs, such goals may presently be
      secondary to service line growth and increased market power. There is reason to
      be cautious about some of the implications of hospital integration of
      cardiologists.

PMID- 30299383
TI  - Working around hierarchy: Resident and medical assistant teaming.
AB  - BACKGROUND: In health care, hierarchy can facilitate getting work done
      efficiently. It can also hinder performance by suppressing valuable contributions
      from lower-positioned individuals. Team-based care could mitigate negative
      effects by creating space for all team members to contribute their unique
      expertise. PURPOSE: This article sought to understand how resident-medical
      assistant (MA) dyads interacted before and after primary care clinics
      transitioned to team-based care. We also studied how they negotiated changes in
      interpersonal dynamics given the challenge these changes presented to
      hierarchical norms. METHODOLOGY: We conducted two qualitative interview studies,
      with 37 residents and 30 MAs at primary care clinics transitioning to team-based
      care. Interviews were transcribed, coded, and analyzed together using a thematic
      networks approach and focused coding. RESULTS: An intervention that promoted
      teamwork prompted resident-MA dyads to change their interactions to counter
      traditional hierarchy. Residents increasingly asked MAs questions about patient
      care, and MAs initiated interactions and volunteered ideas more frequently. We
      also found that MAs and residents expressed some discomfort with the hierarchical
      ambiguity that their new interactions produced and used alternate scripts to
      buffer this discomfort and to collaborate as teammates despite formal hierarchy.
      CONCLUSION: Among resident-MA dyads, a team-based care intervention changed
      interpersonal dynamics by blurring hierarchical lines and shifting traditional
      boundaries in ways that were uncomfortable for both groups. They were able to
      work around discomfort by using new scripts that downplayed the threat to
      hierarchy. PRACTICE IMPLICATIONS: Organizational structures that encourage
      greater interprofessional collaboration may neutralize barriers that formal
      hierarchy in medicine can pose for effective teamwork, but this process can also
      bring social discomfort. Our findings suggest that health care professionals may
      use microlevel strategies, such as alternative scripts, to overcome formal
      hierarchies without openly engaging them. Together, new organizational structures
      and interaction techniques can help professionals work around hierarchy and
      improve team performance.

PMID- 30299384
TI  - Stress, Workplace Violence, and Burnout in Nurses Working in King Abdullah
      Medical City During Al-Hajj Season.
AB  - BACKGROUND: The Hajj pilgrimage to Mecca, one of the largest mass gatherings in
      the world, is associated with various challenges for nurses. One of these
      challenges is increased levels of workplace violence. Therefore, handling and
      mitigating workplace violence against nurses during Hajj, when nurses face a
      higher risk of violence and most experience stress and burnout, is of particular
      importance. PURPOSE: The aims of this study were to identify the types and
      sources of workplace violence, examine the relationship between burnout in nurses
      and the variables of stress and workplace violence, and identify from the
      perspective of nurses measures to effectively handle and mitigate these issues
      during Hajj season. METHODS: This study used a descriptive correlational design.
      A convenience sample of 118 nurses completed the Perceived Stress Scale, the
      Maslach Burnout Inventory, and the modified version of the Joint Programme on
      Workplace Violence in the Health Sector published by the International Labour
      Office in Geneva. Data analysis was done using an independent samples t test and
      Pearson product-moment correlation. RESULTS: One hundred eighteen nurses
      completed the study. Over two thirds (65%) were female, and 56% reported
      experiencing at least one type of violence, of which bullying/mobbing, racial
      harassment, threats, and physical violence accounted for 61%, 15%, 12%, and 12%,
      respectively. Nurse managers displayed violent behaviors against 54% of the
      participants. Participants reported high levels of stress and burnout. A positive
      relationship was found between stress and emotional exhaustion (r = .387, p <
      .01). Providing effective security measures and staff training regarding how to
      deal with violence at the workplace were the main measures identified to help
      reduce workplace violence. CONCLUSIONS: Providing effective security measures and
      tailored intervention programs addressing how to deal with violence in the
      workplace may enable nurses to handle violent behaviors more effectively.

PMID- 30299385
TI  - Reply.

PMID- 30299386
TI  - Age Adjustment of the Psychological Development Questionnaire-1.

PMID- 30299387
TI  - Innate immune cell infiltration in melanoma metastases affects survival and is
      associated with BRAFV600E mutation status.
AB  - Little is known about the infiltrative pattern of innate immune cells in primary
      melanoma compared with their paired metastases and in BRAF-mutated tumors.
      Therefore, our aim was to characterize the inflammatory microenvironment in
      primary ulcerated and nonulcerated melanomas and paired metastases, to
      investigate the relation between inflammation and BRAF mutation in primary
      melanoma and paired metastases, and to evaluate the effect of the analyzed
      biomarkers on melanoma-specific survival. A total of 385 primary tumors and 96
      paired metastases were stained with immunohistochemistry for BRAF, CD163+
      macrophages, CD123+ plasmacytoid dendritic cells, CD66b+ neutrophils, and E
      cadherin and estimated using objective computer-assisted image analysis. BRAF was
      semiquantitatively scored as either present or absent. In metastases of
      nonulcerated melanomas, we observed higher neutrophil (P=0.02) and macrophage
      (P=0.01) numbers. In the metastases of ulcerated melanomas, we found a higher
      number of macrophages (P<0.0001). Increase in the neutrophil numbers in the
      metastases was associated with poor patient survival after first relapse (hazard
      ratio=1.19, 95% confidence interval: 1.03-1.38, P=0.02). BRAF-positive primary
      tumors (P=0.02) and metastases (P=0.01) exhibited increased plasmacytoid
      dendritic cell numbers compared with BRAF-negative tumors. Lastly, primary
      melanomas in men had higher neutrophil numbers than women (P<=0.0001), and men
      had worse melanoma-specific survival (hazard ratio=1.52, 95% confidence interval:
      1.04-2.21, P=0.03). Our data show that melanoma metastases are densely
      infiltrated with neutrophils, which affects survival. Our results also highlight
      the importance of recognizing the presence of inflammatory cells in the
      metastases as a prognostic marker, and that they may potentially be used to
      improve the precision of immunotherapy and BRAF targeted therapy.

PMID- 30299388
TI  - Optimal Emotional Profiles for Peak Performance in Strength and Conditioning.
AB  - Cooper, JJ, Johnson, M, Radcliffe, J, and Fisher, J. Optimal emotional profiles
      for peak performance in strength and conditioning. J Strength Cond Res XX(X): 000
      000, 2018-This study investigated athletes' performance-related emotions and
      emotional profiles for optimal performance in strength and conditioning (S&C). It
      is suggested that the identification and control of emotions associated with
      successful and unsuccessful performances are essential for achieving peak
      psychological states and optimal performance in sports-related tasks. The
      individual zone of optimal functioning (IZOF) model outlines an idiographic and
      comprehensive conceptual framework of interrelated dimensions that describe the
      structure and dynamics of subjective emotional experiences and performance
      related psychobiological states. With institutional ethics approval, 13
      competitive elite athletes (male, n = 7; female, n = 6: mean age = 21.7 +/- 4.0
      years) completed IZOF-based emotion profiling, in which participants were asked
      to recall their perceived best and worst S&C session, outlining emotions and
      intensity within 4 global emotional categories. A significant difference was
      evidenced between best ever and worst ever performance within positive functional
      emotions (p < 0.001, d = 3.63) and negative dysfunctional emotions (p < 0.001, d
      = 4.92). Initial findings suggest that perceived peak performance states within
      S&C are associated with a high intensity of positive functional emotions
      (confident, motivated, and energetic) and a low intensity of negative
      dysfunctional emotions (worn out, sluggish, annoyed, and discouraged). Although
      future research is necessary to fully understand this area, the present data
      suggest that to assist athletes in achieving perceived peak performance states
      within S&C, psychological skills and strategies should be informed and developed
      in collaboration with sport psychologists, with the aim of achieving an optimal
      emotional profile.

PMID- 30299389
TI  - Effect of Velocity-Based Loading on Acceleration Kinetics and Kinematics During
      Sled Towing.
AB  - Bentley, I, Sinclair, JK, Atkins, SJ, Metcalfe, J, and Edmundson, CJ. Effect of
      velocity-based loading on acceleration kinetics and kinematics during sled
      towing. J Strength Cond Res XX(X): 000-000, 2018-Sled towing (ST) provides an
      external load in the form of a sled towed using a shoulder or waist harness and
      cord behind the athlete. Loading strategies have varied greatly between studies,
      and despite many investigations, there is little agreement on the optimum sled
      loading to develop the acceleration phase. The aim of this study was to
      investigate the kinetics and kinematics of velocity-based ST during the
      acceleration phase of sprinting. Twelve academy rugby league players performed a
      series of 6-m sprints in different conditions; uninhibited, 10, 15, and 20%
      velocity decrement (VDec). Sagittal plane kinematics and kinetic measures were
      examined using 1-way repeated-measures analysis of variance. Results indicated
      that ST affected trunk, knee, and ankle joint kinematics (p < 0.05). Peak knee
      flexion increased as sled loads increased (p < 0.05), which may enable athletes
      to lower their center of mass and increase their horizontal force application.
      Net horizontal and propulsive impulse measures were greater in all sled
      conditions (p < 0.05), which increased significantly because sled loadings were
      heavier. In conclusion, this study highlights the effects of differential loads
      to help coaches understand acute kinetics and kinematic changes to improve the
      planning of sprint training.

PMID- 30299390
TI  - A Novel Approach for Athlete Profiling: The Unilateral Dynamic Strength Index.
AB  - Bishop, C, Read, P, Lake, J, Loturco, I, and Turner, A. A novel approach for
      athlete profiling: The unilateral dynamic strength index. J Strength Cond Res
      XX(X): 000-000, 2018-The Dynamic Strength Index (DSI) provides a ratio of the
      peak force an athlete can produce in both isometric and ballistic tasks. Although
      the DSI measured during bilateral tests has been examined, unilateral DSI scores
      have not been reported to date and thus was the aim of the present study. Twenty
      eight recreational sport athletes performed 3 trials of a unilateral isometric
      squat and countermovement jump (CMJ) to measure peak force in each task across 2
      separate test sessions. The unilateral DSI was calculated using both left vs.
      right and dominant vs. nondominant limbs. Good to excellent reliability was shown
      in the isometric squat (intraclass correlation coefficient [ICC] = 0.86-0.96;
      coefficient of variation [CV] <= 5.7%) and the CMJ (ICC = 0.83-0.93; CV <= 5.8%)
      on both limbs. The DSI showed moderate to good reliability (ICC = 0.71-0.79; CV =
      7.54-11.9%). Dynamic Strength Index scores of 0.52-0.55 and 0.55-0.59 were
      reported on the left and right limbs, respectively, with no significant
      differences reported between limbs. A significant difference (p = 0.04) was seen
      for the CMJ between left and right during the second test session only. The
      dominant and nondominant limbs reported mean DSI scores of 0.53-0.57, and
      significant differences were evident between limbs in both the isometric squat
      and CMJ (p < 0.01). This study provides normative data for the unilateral DSI and
      indicates acceptable levels of reliability, whereas the consistency of individual
      measures of peak force can be considered good when quantified unilaterally.

PMID- 30299391
TI  - Comparison of Step-by-Step Kinematics of Elite Sprinters' Unresisted and Resisted
      10-m Sprints Measured With Optojump or Musclelab.
AB  - van den Tillaar, R. Comparison of step-by-step kinematics of elite sprinters'
      unresisted and resisted 10-m sprints measured with Optojump or Musclelab. J
      Strength Cond Res XX(X): 000-000, 2018-The purpose of this study was to compare
      step-by-step kinematics of unresisted and resisted 10-m sprints measured with the
      Optojump or Musclelab on elite sprinters. Six subjects (age 30.0 +/- 5.1 years,
      body mass 76.3 +/- 5.3 kg, body height 1.79 +/- 0.09 m, and 100-m personal best
      10.51 +/- 0.3 s) performed 2 unresisted and 2 sets of 2 resisted (10 and 20% of
      body mass) 30-m sprints in random order (6 sprints in total) in 1 session in
      which kinematics of the first 10 m were measured with the Optojump and Musclelab.
      The main finding was that there were no significant differences between the
      measurements made with the Optojump and Musclelab systems. In addition, it was
      possible to discriminate most kinematic variables per step of the first 10 m when
      different loads (10 and 20% of body mass) had to be pulled during the 30-m
      sprints. The variations in sprint times associated with changes in the resistance
      provided by the dynaSpeed were mainly caused by a decrease in step length as the
      resistance increased. It was concluded that the 2 systems are valid and could
      help coaches, researchers, and athletes by providing more detailed information
      about possible changes to kinematics during training and sprinting with different
      resistances.

PMID- 30299392
TI  - Competition-Based Heart Rate, Training Load, and Time Played Above 85% Peak Heart
      Rate in NCAA Division I Women's Basketball.
AB  - Sanders, GJ, Boos, B, Rhodes, J, Kollock, RO, and Peacock, CA. Competition-based
      heart rate, training load, and time played above 85% peak heart rate in NCAA
      division I women's basketball. J Strength Cond Res XX(X): 000-000, 2018
      Basketball athletes frequently engage in intensities >=85% HRpeak throughout
      competition. Knowing the time spent competing at intensities >=85% HRpeak can
      improve training protocols. The purpose of the study was to assess heart rate
      responses across 4-quarter games (N = 31) in an NCAA division I women's
      basketball season. Ten female athletes were tested and monitored with heart rate
      based wearable microsensor devices. Before the season, HRpeak was recorded
      through a peak metabolic test (V[Combining Dot Above]O2peak). Average (HRavg) and
      HRpeak were recorded for each game, and time spent in 5 heart rate zones
      (HRZones) were recorded: HRZone1 = 50-60% HRpeak, HRZone2 = 60-70% HRpeak,
      HRZone3 = 70-76% HRpeak, HRZone4 = 77-84% HRpeak, and HRZone5 = 85-100% HRpeak.
      Training load was calculated with the summated-heart-rate-zone model (SHRZmod).
      There was a main effect of position (p <= 0.019) and quarter (p <= 0.005) on
      SHRZmod and on time spent in HRZone1-5. Athletes accumulated the most time in
      HRZone4 and HRZone5 and in the fourth quarter, and SHRZmod was the greatest in
      the fourth quarter. There was no main effect for HRavg and HRpeak (p >= 0.110).
      Athletes averaged 34.5 minutes per game competing in HRZone5 or >=85% HRpeak with
      nearly one-third of those minutes accumulated in the fourth quarter. Although
      there were no differences in HRavg and HRpeak from quarter to quarter, SHRZmod
      increased from the first to fourth quarter. Utilizing time spent in heart rate
      zones and training load with SHRZmod can provide valuable information to
      practitioners regarding the intensity and physiological demands of competitive
      basketball games.

PMID- 30299394
TI  - Moderate-Intensity Strength Exercise to Exhaustion Results in More Pronounced
      Signaling Changes in Skeletal Muscles of Strength-Trained Compared With Untrained
      Individuals.
AB  - Lysenko, EA, Popov, DV, Vepkhvadze, TF, Sharova, AP, and Vinogradova, OL.
      Moderate-intensity strength exercise to exhaustion results in more pronounced
      signaling changes in skeletal muscles of strength-trained compared with untrained
      individuals. J Strength Cond Res XX(X): 000-000, 2018-The aim of our
      investigation was to compare the response pattern of signaling proteins and genes
      regulating protein synthesis and degradation in skeletal muscle after strength
      exercise sessions performed to volitional fatigue in strength-trained and
      untrained males. Eight healthy recreationally active males and 8 power-lifting
      athletes performed 4 sets of unilateral leg presses to exhaustion (65% 1
      repetition maximum). Biopsy samples of m. vastus lateralis were obtained before,
      1 and 5 hours after cessation of exercise. Phosphorylation of p70S6k, 4EBP1, and
      ACC increased, whereas phosphorylation of eEF2 and FOXO1 decreased only in the
      trained group after exercise. Expression of DDIT4, MURF1, and FOXO1 mRNAs
      increased and expression of MSTN mRNA decreased also only in the trained group
      after exercise. In conclusion, moderate-intensity strength exercise performed to
      volitional fatigue changed the phosphorylation status of mTORC1 downstream
      signaling molecules and markers of ubiquitin-proteasome system activation in
      trained individuals, suggesting activation of protein synthesis and degradation.
      In contrast to the trained group, signaling responses in the untrained group were
      considerably less pronounced. It can be assumed that the slowdown in muscle mass
      gain as the athletes increase in qualification cannot be associated with a
      decrease in the sensitivity of systems regulating protein metabolism, but
      possibly with inadequate intake or assimilation of nutrients necessary for
      anabolism. Perhaps, the intake of highly digestible protein or protein
      carbohydrate dietary supplements could contribute to the increase in muscle mass
      in strength athletes.

PMID- 30299393
TI  - Effect of the Fatigue on the Physical Performance in Different Small-Sided Games
      in Elite Football Players.
AB  - Calderon Pellegrino, G, Paredes-Hernandez, V, Sanchez-Sanchez, J, Garcia-Unanue,
      J, and Gallardo, L. Effect of the fatigue on the physical performance in
      different small-sided games in elite football players. J Strength Cond Res XX(X):
      000-000, 2018-Football players need to be able to perform high-intensity efforts
      of short duration with brief recovery periods. The aim of this study was to
      analyze the influence of the pitch dimension on high-intensity actions and the
      effect of a repeated sprint ability (RSA) test on the physical performance in
      different 4-against-4 (4v4) small-sided games (SSG) dimensions. Sixteen U-18
      elite football players performed an RSA test between two 4v4 SSGs (pre and post)
      to induce fatigue and compare physical data. Speed, sprint number, accelerations,
      sprint distance, total distance covered, and total distance covered of the
      players at different intensities were evaluated in 3 different SSGs (125, 150,
      250, and 300 m). Results revealed a significant detriment of physical performance
      in the 125-m SSG after RSA, mostly in number of sprints (-6.56; confidence
      interval [CI] 95%: -10.13 to -3.00; effect size [ES]: 1.13 p < 0.001),
      accelerations (-2.69; CI 95%: -5.13 to -0.24; ES: 0.68; p = 0.032), and sprint
      distance (-65.44 m; CI 95%: -103.73 to -27.16; ES: 1.20; p = 0.001). In bigger
      SSGs (250 and 300 m), higher distance at high intensity was covered and Vmax,
      Vmean, and sprint distance were greater. In summary, accelerations, sprint
      number, and fatigue were higher in smaller pitches, and higher velocities were
      reached in bigger SSGs. Football players should be aware that changes in pitch
      size can modify the physical performance on high-intensity actions in SSGs.

PMID- 30299395
TI  - Very early-onset inflammatory bowel disease: an integrated approach.
AB  - PURPOSE OF REVIEW: Immune dysregulation disorders are among the most rapidly
      growing set of inborn errors of immunity. One particular subset is the category
      where early-onset inflammatory bowel disease (IBD) is the most common
      manifestation. These disorders are being increasingly appreciated although there
      has been minimal effort to articulate a unified approach to their diagnosis and
      management. This review will cover current thinking and strategies related to
      diagnosis and management of very early-onset IBD. RECENT FINDINGS: There is an
      expanding set of monogenic causes of early-onset IBD. In many cases, the precise
      genetic cause dictates management. Lessons learned from the management of these
      monogenic conditions can sometimes be extrapolated to other refractory cases of
      IBD. SUMMARY: An integrated approach to diagnosis, risk analysis, and management
      can include diagnostic approaches not often utilized for traditional IBD such as
      whole exome sequencing. Management can also include nontraditional approaches
      such as targeted biologics or hematopoietic cell transplantation.

PMID- 30299396
TI  - Very early onset IBD: novel genetic aetiologies.
AB  - PURPOSE OF REVIEW: To summarize the current understanding and recent advances on
      the genetic aetiology in the pathogenesis of very early onset inflammatory bowel
      disease (VEO-IBD). RECENT FINDINGS: IBD is a chronic disorder of the
      gastrointestinal tract whose manifestation is a result of complex interactions
      between genetics, environment, immune system and microbial flora. Over 230 IBD
      risk loci have been reported in genome wide association studies but the genetic
      contribution of the majority of these loci in the manifestation of IBD is very
      low. Patients with VEO-IBD present with a more severe disease than older
      patients, characterized by poor prognosis and failure of conventional therapy.
      Recent studies have reported several monogenic diseases with high penetrance that
      present with IBD and IBD-like intestinal manifestations and overlap with primary
      immunodeficiencies. Increasing body of evidence supports a prominent role of
      genetics in the onset of VEO-IBD. New genetic variants and diagnoses in VEO-IBD
      are reviewed and current challenges in therapy with potential strategy to manage
      the disease are discussed. SUMMARY: Functional analysis of the genes implicated
      in monogenic IBD has increased the understanding of the underlying
      pathobiological mechanism of the disease. This knowledge can be used to
      personalize medicine for specific patients, improving the standard of care and
      quality of life.

PMID- 30299397
TI  - Biological treatments for severe asthma: where do we stand?
AB  - PURPOSE OF REVIEW: For patients with severe asthma, disease control is not
      achieved resulting in persistent morbidity and risks for exacerbations. The
      advent of biologics is providing a new form of treatment for many with severe
      asthma. RECENT FINDINGS: Four mAb biologics are approved for clinical use:
      omalizumab (anti-IgE) and three antieosinophilic interventions (mepolizumab,
      reslizumab, and benralizumab). These four biologics target components of the type
      2-inflammatory pathway which is reflected by biomarkers: peripheral blood
      eosinophils and exhaled nitric oxide. In severe asthma, biologics have reduced
      asthma exacerbations. The antieosinophilic biologics have also improved lung
      function. The safety profile of these biologics has been good. SUMMARY: For
      patients with severe asthma and biomarkers indicating a type 2 inflammatory
      pathway, the addition of biologics has proven to be an effective approach to
      achieve disease control and is an appropriate next step treatment.

PMID- 30299398
TI  - Secondary antibody deficiency in neurology.
AB  - PURPOSE OF REVIEW: Induction of lymphocyte depletion is increasingly used as a
      therapeutic strategy for central and peripheral neuroinflammatory disease.
      However, there is also a growing recognition of the treatment-related
      complication of secondary antibody deficiency (SAD). Although the occurrence of
      hypogammaglobulinaemia is a recognized phenomenon during immunomodulation, robust
      data on the coexistence of impaired responses to immunization, and significant
      and/or atypical infections is scarce. Here we review the literature on SAD in
      anti-CD20 therapy. RECENT FINDINGS: Several factors that may increase the
      incidence of SAD have now been identified, including low levels of
      immunoglobulins prior to the commencement of B-cell ablation therapy, duration of
      maintenance therapy, and concurrent or prior use of other immunosuppressing
      agents such as cyclophosphamide and steroids. Measurement of disease-specific
      antibodies and vaccine response are likely to be helpful adjuncts to measurement
      of serum immunoglobulin levels during B-cell depleting therapy. Supportive
      treatment may include amending the treatment schedule to limit cumulative dose.
      SUMMARY: B-cell depleting agents offer considerable therapeutic benefit in
      neurology. We propose modifications in current practice that include risk
      stratification and early identification of SAD, with the aim of minimising
      morbidity and mortality related to this underappreciated condition.

PMID- 30299399
TI  - Advances in site-specific gene editing for primary immune deficiencies.
AB  - PURPOSE OF REVIEW: Conventional gene therapy has been a successful, curative
      treatment modality for many primary immune deficiencies with significant
      improvements in the last decade. However, the risk of leukemic transformation
      with viral-mediated gene addition still remains, and unregulated gene addition is
      not an option for certain diseases in which the target gene is closely
      controlled. The recent bloom in genome modification platforms has created the
      opportunity to site-specifically correct mutated DNA base pairs or insert a
      corrective cDNA minigene while maintaining gene expression under control of
      endogenous regulatory elements. RECENT FINDINGS: There is an abundance of ongoing
      research utilizing programmable nucleases to facilitate site-specific gene
      correction of many primary immune deficiencies including X-linked severe combined
      immune deficiency, X-linked chronic granulomatous disease, Wiskott-Aldrich
      syndrome, X-linked hyper-IgM syndrome, X-linked agammaglobulinemia, and immune
      dysregulation, polyendocrinopathy, enteropathy, X-linked. In all, these studies
      have demonstrated the ability to integrate corrective DNA sequences at a precise
      location in the genome at rates likely to either cure or ameliorate disease.
      SUMMARY: Gene editing for primary immune deficiency (PID) has advanced to the
      point to that translation to clinical trials is likely to occur in the next
      several years. At the current pace of research in DNA repair mechanisms, stem
      cell biology, and genome-editing technology, targeted genome modification
      represents the next chapter of gene therapy for PID.

PMID- 30299400
TI  - Daily Stress Processes as Contributors to and Targets for Promoting Cognitive
      Health in Later Life.
AB  - OBJECTIVE: The aim of this study was to test the hypothesis that daily stress
      processes, including exposure and emotional reactivity to daily stressors, are
      associated with response time inconsistency (RTI), an indicator of processing
      efficiency and cognitive health. Furthermore, we considered daily stress
      cognitive health associations at the level of individual differences and within
      persons over time. METHODS: Participants were 111 older adults (Mean=80 years,
      Range=66-95) enrolled in a measurement burst study where assessments of response
      time based cognitive performance, stressful experiences, and affect were
      administered on each of 6 days over a two-week period. This protocol was repeated
      every six months for 2.5 years. Multilevel modeling was used to examine frequency
      of stressor exposure, non-stressor affect, and affect reactivity to daily
      stressors as individual difference and time-varying predictors of RTI. RESULTS:
      Between-persons, higher levels of non-stressor negative affect (b=0.41, 95%CI: 
      0.01, 0.83, p=.055) and negative affect reactivity (b=0.80, 95%CI: 0.18, 1.42,
      p=.012) were associated with greater RTI. Within-persons over time, higher levels
      of negative affect (b=0.20, 95%CI: 0.06, 0.34, p=.006) and negative affect
      reactivity (b=0.13, 95%CI: 0.02, 0.24, p=.018) were associated with increased RTI
      among the oldest portion of the sample, while higher levels of positive affect
      (b=-0.11, 95% CI: -0.21, -0.02, p=.019) were associated with reduced RTI.
      CONCLUSIONS: Negative affect reactions to daily stressors are associated with
      compromised RTI both between- and within-persons. Findings suggest that emotional
      reactions to daily stressors contribute to compromise older adults' cognitive
      health, while increased positive affect may be beneficial.

PMID- 30299401
TI  - The Relationship Between Daytime Salivary Melatonin and Gastrointestinal Symptoms
      in Young Adults Seeking Psychiatric Care.
AB  - OBJECTIVE: The pathophysiology of irritable bowel syndrome (IBS) is not
      completely understood, although we do know that patients with IBS have a high
      prevalence of psychiatric comorbidity (mainly depression and anxiety disorders).
      Melatonin, produced in the gastrointestinal tract, influences gut motility.
      Psychiatric conditions are associated with circadian disturbances in peripheral
      melatonin levels. This study aimed to investigate associations between daytime
      salivary melatonin and gastrointestinal symptoms in young adult psychiatric
      patients. METHODS: Ninety-six patients (86% women), age 18-25 years (mean 21,
      SD=2), seeking psychiatric care with primarily anxiety disorders, affective
      disorders, or both were included in the study. Total scores from The
      Gastrointestinal Symptoms Rating Scale - IBS (GSRS-IBS) were compared with
      salivary melatonin measured at three time points (30 minutes after waking up, at
      11:00 hours and 30 minutes after lunch) during the waking hours of one day.
      RESULTS: When controlling for potential confounders, melatonin levels in saliva
      30 minutes after lunch remained significantly correlated to the total GSRS-IBS
      score after correction for multiple testing (B=0.016, SE=0.006, p=0.015,
      q=0.045). In a post hoc analysis, symptoms of gastrointestinal pain and bloating
      contributed most to this association. CONCLUSIONS: In young adult psychiatric
      patients salivary melatonin levels after lunch are associated with
      gastrointestinal symptoms, which is consistent with the proposed effect of
      elevated levels of gastrointestinal melatonin on gut motility. This result
      suggests a link between IBS symptoms and regulation of melatonin in patients with
      psychiatric disorders.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- 30299402
TI  - Maternal Thyroid Function During Pregnancy or Neonatal Thyroid Function and
      Attention Deficit Hyperactivity Disorder: A Systematic Review.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is the most common
      neurobehavioral disorder in children, yet its etiology is poorly understood.
      Early thyroid hormone disruption may contribute to the development of ADHD.
      Disrupted maternal thyroid hormone function has been associated with adverse
      neurodevelopmental outcomes in children. Among newborns, early-treated congenital
      hypothyroidism has been consistently associated with later cognitive deficits.
      METHODS: We systematically reviewed literature on the association between
      maternal or neonatal thyroid hormones and ADHD diagnosis or symptoms. We searched
      Embase, Pubmed, Cinahl, PsycInfo, ERIC, Medline, Scopus, and Web of Science for
      articles published or available ahead of print as of April 2018. RESULTS: We
      identified 28 eligible articles: 16 studies of maternal thyroid hormones, seven
      studies of early-treated congenital hypothyroidism, and five studies of neonatal
      thyroid hormones. The studies provide moderate evidence for an association
      between maternal thyroid hormone levels and offspring ADHD, some evidence for an
      association between early-treated congenital hypothyroidism and ADHD, and little
      evidence for an association between neonatal thyroid hormone levels and later
      ADHD. CONCLUSIONS: The reviewed articles suggest an association between maternal
      thyroid function and ADHD, and possibly between early-treated congenital
      hypothyroidism and ADHD. Study limitations, however, weaken the conclusions in
      our systematic review, underlining the need for more research. Importantly, there
      was much variation in the measurement of thyroid hormone function and of ADHD
      symptoms. Recommendations for future research include using population-based
      designs, attending to measurement issues for thyroid hormones and ADHD,
      considering biologically relevant covariates (e.g., iodine intake), and assessing
      nonlinear dose-responses.

PMID- 30299403
TI  - The Authors Respond.

PMID- 30299404
TI  - Lifestyle Patterns and Survival Following Breast Cancer in the Carolina Breast
      Cancer Study.
AB  - BACKGROUND: Few studies have examined the impact of lifestyle patterns on
      survival following breast cancer. We aimed to identify distinct lifestyle
      patterns based on five behavior/dietary exposures among a population-based sample
      of women diagnosed with breast cancer and to examine their association with
      subsequent survival. METHODS: In the Carolina Breast Cancer Study Phases I/II, we
      interviewed 1,808 women 20-74 years of age following diagnosis of invasive breast
      cancer. We determined vital status using the National Death Index (717 deaths,
      427 from breast cancer; median follow-up 13.56 years). We assessed lifestyle
      patterns using a latent class analysis based on five behavioral and dietary
      exposures: current versus never/former smokers; low versus high vegetable and
      fruit intake; high and low/moderate, versus no alcohol consumption; and no and
      low/moderate, versus high regular physical activity. We used Cox regression to
      estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals
      (CIs) for all-cause mortality, and cause-specific and subdistribution HRs for
      breast cancer-specific mortality within 5 years and 13 years postdiagnosis
      conditional on 5-year survival. RESULTS: We identified three distinct lifestyle
      patterns: healthy behavior and diet (n = 916); healthy behavior and unhealthy
      diet (n = 624); and unhealthy behavior and diet (n = 268). The unhealthy (vs.
      healthy) behavior and diet pattern was associated with a 13-year conditional all
      cause mortality HR of 1.4 (95% CI = 1.1, 1.9) and with 13-year conditional breast
      cancer-specific and subdistribution HRs of 1.2 (95% CI = 0.79, 1.9) and 1.2 (95%
      CI = 0.77, 1.8), respectively. CONCLUSIONS: Behavioral and dietary patterns can
      be used to identify lifestyle patterns that influence survival patterns following
      breast cancer diagnosis.

PMID- 30299405
TI  - Quality of Maternal Height and Weight Data from the Revised Birth Certificate and
      Pregnancy Risk Assessment Monitoring System.
AB  - BACKGROUND: The 2003 revision of the US Standard Certificate of Live Birth (birth
      certificate) and Pregnancy Risk Assessment Monitoring System (PRAMS) are
      important for maternal weight research and surveillance. We examined quality of
      prepregnancy body mass index (BMI), gestational weight gain, and component
      variables from these sources. METHODS: Data are from a PRAMS data quality
      improvement study among a subset of New York City and Vermont respondents in
      2009. We calculated mean differences comparing prepregnancy BMI data from the
      birth certificate and PRAMS (n = 734), and gestational weight gain data from the
      birth certificate (n = 678) to the medical record, considered the gold standard.
      We compared BMI categories (underweight, normal weight, overweight, obese) and
      gestational weight gain categories (below, within, above recommendations),
      classified by different sources, using percent agreement and the simple kappa
      statistic. RESULTS: For most maternal weight variables, mean differences between
      the birth certificate and PRAMS compared with the medical record were less than 1
      kg. Compared with the medical record, the birth certificate classified similar
      proportions into prepregnancy BMI categories (agreement = 89%, kappa = 0.83);
      PRAMS slightly underestimated overweight and obesity (agreement = 84%, kappa =
      0.73). Compared with the medical record, the birth certificate overestimated
      gestational weight gain below recommendations and underestimated weight gain
      within recommendations (agreement = 81%, kappa = 0.69). Agreement varied by
      maternal and pregnancy-related characteristics. CONCLUSIONS: Classification of
      prepregnancy BMI and gestational weight gain from the birth certificate or PRAMS
      was mostly similar to the medical record but varied by maternal and pregnancy
      related characteristics. Efforts to understand how misclassification influences
      epidemiologic associations are needed.

PMID- 30299407
TI  - Re: Herpesvirus Infection in Infants with Gastroschisis.

PMID- 30299406
TI  - Nonparticipation Selection Bias in the MOBI-Kids Study.
AB  - BACKGROUND: MOBI-Kids is a 14-country case-control study designed to investigate
      the potential effects of electromagnetic field exposure from mobile
      telecommunications devices on brain tumor risk in children and young adults
      conducted from 2010 to 2016. This work describes differences in cellular
      telephone use and personal characteristics among interviewed participants and
      refusers responding to a brief nonrespondent questionnaire. It also assesses the
      potential impact of nonparticipation selection bias on study findings. METHODS:
      We compared nonrespondent questionnaires completed by 77 cases and 498 control
      refusers with responses from 683 interviewed cases and 1501 controls (suspected
      appendicitis patients) in six countries (France, Germany, Israel, Italy, Japan,
      and Spain). We derived selection bias factors and estimated inverse probability
      of selection weights for use in analysis of MOBI-Kids data. RESULTS: The
      prevalence of ever-regular use was somewhat higher among interviewed participants
      than nonrespondent questionnaire respondents 10-14 years of age (68% vs. 62%
      controls, 63% vs. 48% cases); in those 20-24 years, the prevalence was >=97%.
      Interviewed controls and cases in the 15- to 19- and 20- to 24-year-old age
      groups were more likely to have a time since start of use of 5+ years. Selection
      bias factors generally indicated a small underestimation in cellular telephone
      odds ratios (ORs) ranging from 0.96 to 0.97 for ever-regular use and 0.92 to 0.94
      for time since start of use (5+ years), but varied in alternative hypothetical
      scenarios considered. CONCLUSIONS: Although limited by small numbers of
      nonrespondent questionnaire respondents, findings generally indicated a small
      underestimation in cellular telephone ORs due to selective nonparticipation.

PMID- 30299408
TI  - Transfemoral aortic valve implantation with new-generation devices: the
      repositionable Lotus vs. the balloon-expandable Edwards Sapien 3 valve.
AB  - BACKGROUND: New-generation transcatheter heart valves have been developed to
      reduce complications of transcatheter aortic valve implantation (TAVI). With this
      study we sought to compare procedural and 30-day outcomes of the new-generation
      repositionable Boston Scientific Lotus (Lotus) and the balloon-expandable Edwards
      Sapien 3 (ES3) transcatheter heart valves. METHODS: A total of 315 patients with
      severe symptomatic aortic stenosis undergoing transfemoral TAVI with Lotus or ES3
      included in two large Italian registries were considered for this analysis. After
      propensity matching, 93 matched pairs of patients were included. Outcomes were
      evaluated according to Valve Academic Research Consortium-2 definition at
      discharge and 30 days. RESULTS: There were no differences in baseline
      characteristics, except for lower mean aortic gradient and larger mean aortic
      annulus in the ES3-treated patients. Valve Academic Research Consortium-2 defined
      device success was high and comparable between groups (97.8 for Lotus vs. 98.9%
      for ES3, P = 0.09). The frequency of moderate/severe paravalvular leak was low
      and similar for both devices (2.2 vs. 1.1%, P = 0.10). At 30 days, both groups
      showed low all-cause mortality (5.4 vs. 1.1%, P = 0.10) and rates of disabling
      stroke (3.2 vs. 1.1%, P = 0.31). New pacemaker implantation was more common after
      Lotus deployment (31.7 vs. 10.5%, P < 0.001). CONCLUSION: Transfemoral TAVI with
      both Lotus and ES3 resulted in favorable clinical and hemodynamic procedural and
      30-day outcomes. Rates of significant paravalvular leak were low with both
      devices. The Lotus valve was associated with higher risk of pacemaker
      implantation.

PMID- 30299410
TI  - Carotid Doppler assessment in patients undergoing transcatheter aortic valve
      implantation.

PMID- 30299409
TI  - Safety and effectiveness of the transsubclavian approach for transcatheter aortic
      valve implantation with the 14-F CoreValve Evolut R device.
AB  - AIMS: In addition to the transfemoral route, common approaches for transcatheter
      aortic valve implantation (TAVI) are the transapical and transaortic ones. Yet,
      these are associated with morbidity. The transsubclavian approach (TSA) is an
      alternative to minimize invasiveness. METHODS: Fifteen consecutive patients
      underwent TAVI via TSA using the CoreValve Evolut R. The 14F delivery system
      without sheath was directly introduced into the artery. RESULTS: Success was
      100%; contrast volume was 99.4 +/- 29.58 ml. Patients were extubated after 1.66
      +/- 0.89 h. Hemoglobin drop was 0.64 +/- 0.28 g/dl. There were no complications.
      Hospital stay was 4.53 +/- 1.24 days: 11 patients were discharged home, the
      remainder to rehabilitation. CONCLUSION: TSA is associated with limited
      morbidity, early patient mobilization, short hospitalization.

PMID- 30299411
TI  - Use of newly designed graphs for depicting network meta-analyses: how to
      summarize difficult calculations with visual immediateness.

PMID- 30299412
TI  - Sucrose but Not Nitrate Ingestion Reduces Strenuous Cycling-induced Intestinal
      Injury.
AB  - PURPOSE: Strenuous exercise induces intestinal injury, which is likely related to
      splanchnic hypoperfusion and may be associated with gastrointestinal complaints
      commonly reported during certain exercise modalities. Increasing circulating
      nitric oxide (NO) levels or inducing postprandial hyperemia may improve
      splanchnic perfusion, thereby attenuating intestinal injury during exercise.
      Therefore, we investigated the effects of both dietary nitrate ingestion and
      sucrose ingestion on splanchnic perfusion and intestinal injury induced by
      prolonged strenuous cycling. METHODS: In a randomized cross-over manner, 16 well
      trained male athletes (age: 28+/-7 y; Wmax: 5.0+/-0.3 W.kg) cycled 60 min at 70%
      Wmax following acute ingestion of: sodium nitrate (NIT; 800 mg NO3), sucrose
      (SUC; 40 g) or a water placebo (PLA). Splanchnic perfusion was assessed by
      determining the gap between gastric and arterial pCO2 (gapg-apCO2) using gastric
      air tonometry. Plasma intestinal fatty-acid binding protein (I-FABP)
      concentrations, reflecting enterocyte damage, were assessed every 20 min during
      and up to 60 min of post-exercise recovery. RESULTS: The exercise protocol
      resulted in splanchnic hypoperfusion, as gapg-apCO2 levels increased during
      exercise (P<0.001), with no differences between treatments (P=0.47). Although
      plasma I-FABP concentrations increased during exercise and post-exercise recovery
      for all treatments (P<0.0001), the increase was different between treatments
      (P<0.0001). Post-hoc comparisons showed an attenuated increase in I-FABP in SUC
      vs PLA (P=0.020). In accordance, I-FABP area under the curve (AUC0-120) was
      significantly lower in SUC vs PLA (57,270+/-77,425 vs 114,907+/-91,527 pg.mL.120
      min, P=0.002). No differences were observed between NIT and PLA (P=0.99).
      CONCLUSION: Sucrose but not nitrate ingestion lowers intestinal injury evoked
      during prolonged strenuous cycling. These results suggest that sucrose ingestion,
      but not nitrate, prevents hypoperfusion-induced gastrointestinal damage during
      exercise and, as such, may help to lower exercise-related gastrointestinal
      complaints.

PMID- 30299414
TI  - To the Editor.

PMID- 30299413
TI  - Supplemental Oxygen Does Not Influence Self-selected Work Rate at Moderate
      Altitude.
AB  - INTRODUCTION: It is well known that supplemental oxygen can increase aerobic
      power output during high-intensity and/or maximal efforts at moderate altitude,
      yet the effects on self-selected work rate during lower-intensity, submaximal
      exercise are unknown. We reasoned that if the degree of arterial oxygen
      saturation (SaO2) influences teleoanticipatory regulation of power output,
      supplemental oxygen given at moderate altitude would increase average power
      output during exercise performed at self-selected work rates corresponding to RPE
      9 (very light) and 13 (somewhat hard). METHODS: Twenty-three subjects (17 males,
      6 females) completed one familiarization [fraction of inspired O2 (FIO2)=0.209]
      and two blinded, experimental trials (FIO2=0.209 and FIO2=0.267). In each trial,
      subjects self-regulated their work rate on a cycle ergometer to maintain RPE 9
      for 5 min and RPE 13 for 10 min, before performing an incremental step test to
      exhaustion (25 W/min). Oxygen consumption (VO2) and SaO2 via pulse oximetry
      (SpO2) were continuously monitored. Subjects were asked to guess the experimental
      condition after each stage of the protocol. RESULTS: Supplemental oxygen
      increased SpO2 throughout exercise (~4%; P<0.001) and was associated with greater
      peak power output (4+/-4%; P<0.001) and VO2 (5+/-10%; P=0.010) during the
      incremental test, but did not increase average power output selected during
      exercise at RPE 9 (P=0.235) or 13 (P=0.992). Subjects were unable to perceive the
      difference in FIO2 at any stage (P>0.14). CONCLUSIONS: Small increases in
      inspired oxygen concentration at moderate altitude are imperceptible and do not
      appear to influence selection of submaximal work rates at RPE <= 13.

PMID- 30299415
TI  - Closed Wound Sub-Fascial Suction Drainage in Posterior Fusion Surgery for
      Adolescent Idiopathic Scoliosis: A Prospective Randomize Control study.
AB  - STUDY DESIGN: Prospective randomized control study. OBJECTIVE: To compare the
      complication rate in adolescent idiopathic scoliosis (AIS) posterior spinal
      fusion (PSF) surgery with and without drainage. SUMMARY OF BACKGROUND DATA: PSF
      is the mainstay of surgical treatment for AIS. Drains are commonly used despite
      contradictory findings in the literature for their having any clear advantage.
      METHODS: A total of 100 AIS patients undergoing instrumented PSF were blindly
      randomized into 2 groups of either a deep drain or no drain. The collected data
      included wound follow-up findings, hemoglobin, hematocrit, vital signs and fever
      levels, and mean 20 months follow-up. RESULTS: Fifty-two patients were randomly
      allocated to the "no drain" group and 48 to the "drain" group. There were no
      differences in patient characteristics, surgical data and hemoglobin and
      hematocrit levels between the 2 groups. Only 4 units of packed cells were given
      in total. Fever during the first postoperative 1-3 days was equal, but increased
      in the no drain group on day 6 (P = 0.017). Length of hospitalization was equal
      (6 days) for all the patients. The mean follow-up period was 20 months [8.5-30.7
      (SD 6.4)]. Complications included one case (1.9%) of pneumonia in the "no-drain"
      group, wound dehiscence in 2 cases (3.8%) in the "no-drain" group and in one case
      (2.1%) in the "drain" group, and 2 cases (3.8%) of superficial wound infection in
      the "no-drain" group. There was no case of deep infection in either group.
      CONCLUSION: The current results indicate that there is no advantage to deep
      drainage in AIS patients undergoing PSF. The number of wound healing
      complications was low and identical for both the drain and no-drain groups. LEVEL
      OF EVIDENCE: 2.

PMID- 30299416
TI  - Don't you wish you had fused to the pelvis the first time: a comparison of
      reoperation rate and correction of pelvic obliquity.
AB  - STUDY DESIGN: Multicenter retrospective OBJECTIVE.: To compare pelvic obliquity
      correction and reoperation rate in neuromuscular scoliosis patients who had their
      pelvis included in a posterior spinal fusion (pelvic fusion, PF) at their index
      procedure vs revision procedures. SUMMARY OF BACKGROUND DATA: There is limited
      information on outcomes specific to fusing to the pelvis for neuromuscular
      scoliosis in a revision operation versus index surgery. METHODS: Charts and
      radiographs were reviewed of patients with PF for neuromuscular scoliosis from
      01/2003 to 08/2015 at 4 high volume pediatric spine centers with > 2 year follow
      up. RESULTS: 285 patients met inclusion criteria; 271 had PF done at index
      surgery and 14 had PF done during revision surgery. Prior to index procedure,
      there were no significant differences in Cobb angle (p = 0.13). Prior to pelvic
      fusion there was no difference in pelvic obliquity (p = 0.26). At the time of
      fusion to the pelvis, estimated blood loss (p = 0.23) and operative time (p =
      0.43) did not differ between index and revision groups. Percent correction in
      pelvic obliquity was similar for both groups (p = 0.72). Overall, 69 patients had
      complications requiring return to the OR. Excluding the revision surgery for
      inclusion of the pelvis for the revision group, there was still a lower
      reoperation rate with index PF (22.9%, n = 62/271) than revision PF (50.0%, n =
      7/14) (p = 0.02). Implant failures were significantly higher in the revision
      group (index = 7.4%, 20/271; revision = 42.9%, 6/14; p < 0.001). CONCLUSION: PF
      at the index spinal fusion led to similar correction of pelvic obliquity with
      approximately half the reoperation rate compared to PF at a revision surgery.
      Operative time and blood loss were similar between index and revision spinal
      fusion. LEVEL OF EVIDENCE: 4.

PMID- 30299417
TI  - How common is medial and lateral shoulder discordance in lenke 1 and 2 curves? a
      preoperative analysis of medial and lateral shoulder balance among 151 lenke 1
      and 2 adolescent idiopathic scoliosis (AIS) patients.
AB  - STUDY DESIGN: .: Retrospective study of prospectively collected data. OBJECTIVE:
      .: To analyze the incidence and the patterns of medial and lateral shoulder
      discordance among Lenke 1 and 2 patients. SUMMARY OF BACKGROUND DATA: .:
      Postoperative shoulder imbalance (PSI) is still common in Lenke 1 and 2 AIS. This
      could be due to presence of medial dan lateral shoulder discordance. METHODS: .:
      151 patients with Lenke 1 and 2 AIS were recruited. Lenke 1 were subclassified
      into Lenke 1-ve (PTSB Cobb angle < 15 degrees ) and 1 + ve (PTSB Cobb angle
      between 15 degrees  to 24.9 degrees ). T1 tilt represented "medial shoulder
      balance" and Radiological Shoulder Height (RSH) represented "lateral shoulder
      balance". We categorized patients into 3 concordant shoulder pattern types
      (Medial Balanced/ Lateral Balanced (MBLB), Medial Imbalanced + ve/ Lateral
      Imbalanced + ve (MI + ve/LI + ve), Medial Imbalanced -ve/ Lateral Imbalanced -ve
      (MI-ve/LI-ve) and 6 discordant shoulder types. RESULTS: .: The mean age was 16.2
      +/- 5.7 years. 81 patients (53.6%) had concordant patterns and 70 patients
      (46.4%) with discordant patterns. Lateral shoulder imbalance was 35.1% and medial
      shoulder imbalance was 43.7%. In Lenke 1-ve curves, 35 patients (68.6%) had
      concordant imbalance with Medial Imbalanced -ve/ Lateral Imbalanced -ve (MI-ve/LI
      ve) being the commonest (68.6%). In Lenke 1 + ve curves, 33 patients (55.0%) had
      concordant patterns with Medial Balanced/ Lateral Balanced (MB/LB) being the
      commonest type (57.6%). In Lenke 2 AIS, 27 patients (67.5%) were discordant with
      Medial Imbalanced + ve/ Lateral Balanced (MI + ve/LB) being the commonest pattern
      (44.4%) (p value = 0.002). CONCLUSION: .: 46.4% Lenke 1 and 2 AIS patients had
      shoulder discordant pattern. This was more prevalent in Lenke 2 curves (67.5%).
      In Lenke 1-ve curves, MI-ve/LI-ve pattern was the commonest. In Lenke 1 + ve
      curves, both concordant and discordant groups were almost equal. In Lenke 2 AIS,
      the most common shoulder pattern was MI + ve/LB pattern. LEVEL OF EVIDENCE: 4.

PMID- 30299418
TI  - Skeletal Muscle Cell Oxidative Stress As A Possible Therapeutic Target In A
      Denervation-Induced Experimental Sarcopenic Model.
AB  - STUDY DESIGN: A basic study using a rodent model of sarcopenia. OBJECTIVE: To
      elucidate the contribution of oxidative stress to muscle degeneration and the
      efficacy of antioxidant treatment for sarcopenia using an animal model of
      neurogenic sarcopenia. SUMMARY OF BACKGROUND DATA: Oxidative stress has been
      reported to be involved in a number of pathologies, including musculoskeletal
      disorders. Its relationship with sarcopenia, one of the potential origins of
      lower back pain, however, is not yet fully understood. METHODS: Myoblast cell
      lines (C2C12) were treated with H2O2, an oxidative stress inducer, and N-acetyl-L
      cysteine (NAC), an antioxidant. Apoptotic effects induced by oxidative stress and
      the antioxidant effects of NAC were assessed by western blotting,
      immunocytochemistry, and MTT cell viability assays. An animal model of sarcopenia
      was produced via axotomy of the sciatic nerves to induce muscle atrophy. Twenty
      four male Sprague-Dawley rats were divided into sham, sham+NAC, axotomy, and
      axotomy+NAC groups. Rats were provided water only or water containing NAC (1 g/L)
      for four weeks. The gastrocnemius muscle was isolated and stained with
      hematoxylin and eosin (H&E) two weeks after axotomy, from which muscle cells were
      harvested and protein extracted for evaluation. RESULTS: Mitogen-activated
      protein kinases (MAPKs) were significantly activated by H2O2 treatment in C2C12
      cells, which was ameliorated by NAC pretreatment. Furthermore, H2O2 induced
      apoptosis and death of C2C12 cells, which was prevented by NAC pretreatment. The
      weight of the gastrocnemius muscle was reduced in the axotomy group, which was
      prevented by NAC administration. Lastly, although muscle specimens from the
      axotomy group showed greater reductions in muscle fiber, the oral administration
      of NAC significantly inhibited amyotrophy via antioxidant effects. CONCLUSIONS:
      The current in vitro and in vivo study demonstrated the possible involvement of
      oxidative stress in sarcopenic pathology. NAC represents a potential anti
      sarcopenic drug candidate, preventing amyotrophy and fatty degeneration. LEVEL OF
      EVIDENCE: 4.

PMID- 30299419
TI  - Recognition of Insufficient Competence-Nurses' Experiences in Direct Involvement
      With Adolescent Children of Cancer Patients.
AB  - BACKGROUND: A parent's cancer may have disruptive impact on his/her adolescent
      children. Currently, nurses have been regarded as central actors in direct
      involvement with patients' minor children. Development of an extended nursing
      role has become a pertinent issue. OBJECTIVE: Adolescents' needs tend to be
      overlooked by nurses because of inexperience with this population. The aim of
      this study was to explore nurses' experiences of direct involvement with these
      adolescents, to get a deeper understanding about this phenomenon. METHODS: Using
      a constructivist grounded theory approach, 12 interviews were conducted among
      Norwegian nurses within the cancer care context. The category insufficient
      competence was explored through analyzing participants' experiences of direct
      involvements with adolescents. RESULTS: The recognition of insufficient
      competence became visible as nurses experienced being involved with a population
      about whom they held inadequate and limited knowledge. Adolescents were perceived
      as unpredictable and rejecting nurses' approaches. Consequently, nurses feared
      involvement and experienced failing on their assignments. After completing more
      or less failed attempts to establish good relationships with adolescents, the
      nurses requested for more knowledge and experience in order to support this
      group. CONCLUSIONS: Nurses are recognizing insufficient competence in direct
      involvement with adolescents, which calls for extended competence. Because nurses
      are not the only responsible actors performing in this field, building competence
      requires a broadened attention at both an individual and organizational level,
      across several healthcare disciplines, as well as through user participation.
      IMPLICATIONS FOR PRACTICE: Competence building should be considered in light of
      organizational frameworks, collective learning possibilities across disciplines,
      and opportunities for involving adolescents/young adults as user participants.

PMID- 30299420
TI  - Does the Oral Administration of Ginger Reduce Chemotherapy-Induced Nausea and
      Vomiting?: A Meta-analysis of 10 Randomized Controlled Trials.
AB  - BACKGROUND: Preclinical tests in animals have shown that ginger extract can be
      used to treat chemotherapy-induced nausea and vomiting (CINV); however, research
      findings in clinical trials have not been conclusive. OBJECTIVE: Through this
      meta-analysis, we aimed to determine whether ginger could be used to treat CINV,
      which was interpreted using the PICOS (patient, problem/population, intervention,
      comparison, outcome, study) framework, with P being patients who underwent
      chemotherapy; I being 0.5 to 2.0 g/d of Zingiberaceae, Zintoma, dry ginger,
      ginger capsules, powdered ginger root, Zingiber officinale Roscoe, ginger
      extract, powdered ginger, 6-gingerol, or shogalos; C being placebo or standard
      care; and O being the relief, reduction, or improvement of CINV. METHOD: Via
      systematic literature review, we searched for studies in English from 2000 to
      2017 in databases. We conducted a meta-analysis using Comprehensive Meta-analysis
      2 on a total of 10 studies with complete data. RESULTS: The odds ratio (OR) of
      ginger in controlling CINV was 0.71 (95% confidence interval [CI], 0.54-0.94; P =
      .015). Heterogeneity existed among the samples; therefore, we proceeded with a
      subgroup analysis and divided nausea and vomiting into acute or delayed. The
      results revealed that ginger could only reduce acute CINV in patients (OR, 0.60;
      95% CI, 0.42-0.86; P = .006), particularly acute vomiting (OR, 0.58; 95% CI, 0.37
      0.94; P = .025). CONCLUSIONS: Ginger displayed significant efficacy with regard
      to controlling CINV in the experimental groups. IMPLICATIONS FOR PRACTICE: Our
      results could provide a reference for antiemetic methods to treat CINV and
      facilitate support for more clinical trials in the future to establish relevant
      guidelines.

PMID- 30299421
TI  - Association of Time-Varying Rest-Activity Rhythm With Survival in Older Adults
      With Lung Cancer.
AB  - BACKGROUND: To the best of our knowledge, this is the first study to examine the
      relationship of rest-activity rhythm with survival in older adults with lung
      cancer and to consider variations in rest-activity rhythm over time. OBJECTIVE:
      The aim of this study was to explore the relationship between rest-activity
      rhythm variations and survival in 33 older adults with lung cancer by considering
      rest-activity rhythm as a time-dependent covariate over time. METHODS: In this
      prospective study with 5 repeated measurements, patients' rest-activity rhythm
      over 3 days was measured using actigraphy. The rest-activity rhythm was
      represented using the dichotomy index I (in-bed activity) < O (out-of-bed
      activity). The median I < O was used as the cutoff point, with an I < O of
      greater than or equal to 85.59% and less than 85.59% indicating robust and
      disrupted rest-activity rhythms, respectively. Data were analyzed using the Cox
      regression model with time-dependent repeated measurements of a covariate.
      RESULTS: In the time-dependent multivariate Cox model, a disrupted rest-activity
      rhythm was independently associated with a higher risk of death than was a robust
      rest-activity rhythm (hazard ratio, 16.05; P=.009). CONCLUSION: A time-varying
      rest-activity rhythm is incrementally associated with mortality in older adults
      with lung cancer and represents a rigorous and independent prognostic factor for
      their survival. IMPLICATIONS FOR PRACTICE: Clinicians may need to pay more
      attention to the rest-activity rhythms of older adults with lung cancer during
      disease progression. Future studies should account for the variation in rest
      activity rhythm over time.

PMID- 30299422
TI  - Impact of the 2017 Blood Pressure Guidelines by the American Academy of
      Pediatrics in overweight/obese youth.
AB  - OBJECTIVES: The aim of this study was to compare the impact of the European
      Society of Hypertension Guidelines 2016 (ESHG2016) and the American Academy of
      Pediatrics Guidelines 2017 (AAPG2017) on the screening of hypertension and
      classification of abnormal left ventricular geometry (ALVG) in overweight/obese
      youth. METHODS: This study included 6137 overweight/obese youth; 437 had
      echocardiographic assessment. Hypertension was defined using either ESHG2016 or
      AAPG2017. ALVG was defined using 95th percentile for age and sex of left
      ventricular mass index (LVMi) and/or relative wall thickness (RWT) more than 0.38
      (juvenile cut-offs) according to ESHG2016 or LVMi more than 51 g/h and/or RWT
      more than 0.42 (adult cut-offs) according to AAPG2017. RESULTS: Prevalence of
      youth at a high risk of hypertension was 13% higher using AAPG2017 than ESHG2016.
      The increase was larger in overweight youth at least 13 years of age (+43%).
      Using the juvenile cut-offs for ALVG, youth at a high risk of hypertension by
      ESHG2016 had an odds ratio [95% confidence interval (95% CI)] of 3.03 (1.31-7.05)
      for left ventricular concentric remodelling (LVcr) and 2.53 (1.43-4.47) for
      concentric left ventricular hypertrophy (cLVH) as compared with youth with normal
      LVG. Similarly, in youth at a high risk of hypertension by AAPG2017, the odds
      ratio for LVcr was 3.28 (1.45-7.41, P < 0.001) and 3.02 (95% CI: 1.73-5.27, P <
      0.001) for cLVH. Using the adult cut-offs, no significant difference in ALVG was
      found with both guidelines. CONCLUSION: The prevalence of overweight/obese youth
      at a high risk of hypertension increased by 13% comparing AAPG2017 vs. ESHG2016.
      The juvenile cut-offs for ALVG were more effective than the adult criteria in
      intercepting individuals with a potentially higher cardiovascular risk.

PMID- 30299423
TI  - Group B Streptococcal Neonatal and Early Infancy Infections in Iceland 1976 -
      2015.
AB  - BACKGROUND: Despite a risk-based peripartum chemoprophylaxis approach in Iceland
      since 1996, Streptococcus agalactiae (GBS) remains an important cause of early
      onset (<7 days, EOD) and late-onset disease (7 days to 3 months, LOD). METHODS:
      We studied GBS invasive disease in children <1 year in Iceland in 1976-2015.
      Bacteria (n=98) were characterized by susceptibility to a panel of
      antimicrobials, capsular serotyping, resistance genes, surface protein and pilus
      locus profiling, and multilocus sequence typing. RESULTS: Both EOD and LOD
      increased during the early years, but while EOD subsequently decreased from
      0.7/1000 live births in 1991-1995 to 0.2/1000 in 2011-2015, LOD showed a non
      significant decrease from its peak value of 0.6/1000 in 2001-2005 to 0.4/1000 in
      2006-2015. Serotype III was the most frequently found (n=48), represented mostly
      by the hypervirulent lineage CC17/III/rib/PI-1+PI-2b (62%), but also by
      CC19/III/rib/PI-1+PI-2a (35%) frequently associated with colonization. Serotype
      Ia (n=22) was represented by CC23/Ia/eps/PI-2a (68%), and CC7/Ia/bca/PI-1+PI-2b
      (23%) of possible zoonotic origin. Resistance to erythromycin and clindamycin was
      increasingly detected in the last years of the study (five out of the nine cases
      were isolated after 2013), including representatives of a multiresistant
      CC17/III/rib/PI-2b sublineage described recently in other countries and
      expressing resistance to erythromycin, clindamycin and streptomycin. CONCLUSIONS:
      The risk-based chemoprophylaxis adopted in Iceland possibly contributed to the
      decline of EOD but has had limited effect on LOD. GBS causing neonatal and early
      infancy invasive infections in Iceland are genetically diverse and the recent
      emergence of antimicrobial resistant lineages may reduce the choices for
      prophylaxis and therapy of these infections.

PMID- 30299424
TI  - Respiratory Microbiota Predicts Clinical Disease Course of Acute Otorrhea in
      Children With Tympanostomy Tubes.
AB  - BACKGROUND: Acute otitis media (AOM) is one of the most common childhood
      infections, generally thought to be caused by ascension of bacteria from the
      nasopharynx (NP) to the middle ear. Using 16S rRNA-based sequencing, we evaluated
      the relationship between the NP and middle ear fluid (MEF) microbiota in children
      with acute otitis media with tympanostomy tubes (AOMT) as a proxy for AOM, and
      explored whether microbiota profiling predicts natural disease course. METHODS:
      Microbiota profiles of paired NP and MEF samples of 94 children aged below five
      years with uncomplicated AOMT were determined. RESULTS: Local diversity (p<0.001)
      and overall microbiota composition (p<0.001) of NP and MEF samples differed
      significantly, though paired NP and MEF samples were much more similar than
      unpaired samples (p<0.001). High qualitative agreement between the presence of
      individual bacteria in both niches was observed. Abundances of Pseudomonas
      aeruginosa, Staphylococcus aureus, Streptococcus pyogenes, Turicella otitidis,
      Klebsiella pneumoniae, and Haemophilus spp. were strongly correlated between the
      two niches. Additionally, P. aeruginosa, S. aureus, T. otitidis and Streptococcus
      pneumoniae abundance in NP were predictive of the presence of a range of oral
      types of bacteria in MEF. Interestingly, there was no association between
      Moraxella catarrhalis in NP and MEF samples, which was highly present in NP but
      virtually absent in MEF. Finally, the NP microbiota composition could predict
      duration of AOMT, even better than MEF microbiota. CONCLUSIONS: We observed
      substantial correlations between paired NP and MEF microbiota in children with
      AOMT. Our data also suggest that NP microbiota profiling deserves further
      exploration as tool for future treatment decisions.

PMID- 30299425
TI  - Scabies: New Opportunities for Management and Population Control.

PMID- 30299426
TI  - A Teenage Girl With Aseptic Meningitis and Abdominal Pain.

PMID- 30299427
TI  - Impact of Disease on Amikacin Pharmacokinetics and Dosing in Children.
AB  - BACKGROUND: Amikacin is widely used to treat severe Gram-negative bacterial
      infections. Its peak concentration in plasma is associated with treatment
      efficacy. Amikacin pharmacokinetics (PK) is influenced by disease conditions, in
      addition to other patient characteristics. In this retrospective study, we
      evaluated the impact of clinical characteristics and disease condition on
      amikacin PK in children with burn injuries and those with cancer. METHODS:
      Amikacin PK data from 66 children with burn injuries and 112 children with cancer
      were analyzed. A population PK model was developed using the non-linear mixed
      effects modeling approach. Models were developed using NONMEM 7.3 (ICON
      Development Solutions, LLC, Ellicott City, MD, USA). Data processing and
      visualization was performed using R packages. RESULTS: The amikacin PK data was
      best described by a 2-compartment model. The parameters were estimated with means
      (95% confidence intervals) as follows: central volume of distribution (V1), 5.70
      L (4.64-6.76 L); central clearance (CL), 2.12 L/h (1.79-2.46 L); peripheral
      volume of distribution (V2), 4.79 L (2.36-7.22 L); distribution clearance (Q),
      0.71 L/h (0.25-1.16 L/h). The final model identified the disease condition as a
      significant covariate, and indicated 55% (28% - 82%) higher CL and 17% (1% - 34%)
      higher V1 in burn patients compared with cancer patients. Volume of distribution
      was significantly influenced by age and body weight. Clearance was significantly
      influenced by age, body weight and creatinine clearance. Using the final PK
      model, we developed a workflow for selecting optimal dosing strategies for three
      representative pediatric patient profiles. CONCLUSION: Disease condition was
      significant in influencing amikacin PK in children. To reach the same target
      concentrations (64 mg/L peak concentration) with a daily dose plan, burn patients
      need higher doses than cancer patients. Future investigations are needed to
      explore the impact of other diseases on amikacin disposition in children, and to
      prospectively validate the proposed dosing strategy.

PMID- 30299428
TI  - Pharmacodynamic monitoring of biological therapies in chronic inflammatory
      diseases.
AB  - BACKGROUND: Psoriasis, psoriatic arthritis, spondyloarthritis, rheumatoid
      arthritis, ulcerative colitis and Crohn's disease share similar underlying
      pathophysiological processes, providing the opportunity to treat the patients
      using similar biological therapies. Failure of biological treatments due to
      underexposure can be managed by therapeutic drug monitoring. Adjusting the
      treatment based on pharmacokinetic monitoring can be further improved by taking
      pharmacodynamic parameters such as clinical and molecular markers into account.
      METHODS: Here, we critically evaluate the existing evidence, the hurdles to be
      taken and the opportunities for a widespread implementation of pharmacodynamic
      monitoring. RESULTS: Pharmacodynamic monitoring typically is the monitoring of
      biochemical markers. A pharmacodynamic marker preferably is specific for the
      pharmacological action of a drug, but most of the time nonspecific
      pharmacodynamic markers are used, like C-reactive protein and the erythrocyte
      sedimentation rate. Clinical pharmacodynamic markers typically evaluate physical
      variables or symptoms. While physician-reported outcomes have been studied for a
      longer time and often have been shown to correlate well with molecular
      pharmacodynamic markers and treatment outcomes, the introduction of mobile health
      or mHealth technologies caused a shift towards patient-reported outcomes, with
      the associated challenge to consistently reflect the inflammatory state, thereby
      preventing undertreatment or unnecessary overdosing of patients. CONCLUSIONS: The
      primary goal of pharmacodynamic monitoring is to optimize the response, but it
      can also have an impact on safety, costs, patient adherence, etc. Ideally, the
      constant remote monitoring of patient-reported disease activity is expected to
      become the standard, facilitated by mHealth technologies.

PMID- 30299429
TI  - Estimation of unbound carboplatin clearance from total plasma concentrations as a
      means of facilitating therapeutic drug monitoring.
AB  - BACKGROUND: Therapeutic drug monitoring of carboplatin is based on its unbound
      clearance (CLU) determined by Bayesian analysis on unbound (U) concentrations.
      However, the ultrafiltration of plasma samples presents technical and time
      constraints. Therefore, the present study aims to estimate CLU using total plasma
      (P) concentrations. METHODS: U and P concentration data of 407 patients were
      obtained from two clinical studies in which actual CLU had been determined for
      each patient. The patients were then split into development (277 patients) and
      prospective datasets (130 patients). Two approaches were evaluated. PK-model-only
      approach: a three-compartment pharmacokinetic (PK) model based on U and P
      concentrations and taking into account the protein binding process was developed.
      The model with patient covariates was also evaluated. Linear regression approach:
      an equation (CLU = a.CLP + b) was obtained by linear regression analysis between
      actual CLU and CLP which is the total plasma clearance obtained by analyzing P
      concentrations according to a two-compartment PK model. Predictive performance
      was then assessed within the prospective dataset by estimating CLU from P
      concentrations using each approach and computing the relative percentage error
      (PE) between estimated CLU and actual CLU. RESULTS: The linear regression
      equation was CLU (L/h) = 1.15 CLP (L/h) + 0.13. The mean PE (MPE) between CLU
      (estimated using the equation) and the actual CLU was +1.2% (ranging from -31% to
      +33%) and the mean absolute PE (MAPE) was 9.7%. With the three-compartment PK
      model, the MPE was +2.3% (ranging from -41% to +31%), and the MAPE was 11.1%.
      Inclusion of covariates in the three-compartment model did not improve the
      estimation of CLU [MPE: +6.3% (from -33% to +37%); MAPE=11.4%]. CONCLUSIONS: The
      linear equation gives a relatively good estimation of CLU based on P
      concentrations, making PK-based carboplatin dose adaptation possible for centers
      without ultrafiltration facilities.

PMID- 30299430
TI  - A Short Communication: Pharmacokinetic characteristics and limited sampling
      strategies for therapeutic drug monitoring of colistin in patients with multidrug
      resistant Gram-negative bacterial infections.
AB  - BACKGROUND: Colistin is increasingly used as the last therapeutic option for the
      treatment of multidrug-resistant, Gram-negative bacterial infections. To ensure
      safe and efficacious use of colistin, therapeutic drug monitoring (TDM) is needed
      due to its narrow therapeutic window. This study aimed to evaluate the
      pharmacokinetic (PK) characteristics of colistin and to guide TDM in colistin
      treated patients in Korea. METHODS: In a prospective study, we analysed PK
      characteristics in 15 patients who intravenously received colistin
      methanesulfonate (CMS) twice per day. CMS doses were adjusted based on renal
      function of the subjects. The appropriate blood sampling points for TDM were
      evaluated by analysing the correlations between the PK parameters and the plasma
      concentrations at each time point. RESULTS: The mean values for the minimum,
      maximum and average concentrations (Cmin, Cmax and Caverage) of colistin at
      steady state were 2.29, 5.5 and 3.38 mg/L, respectively. The dose-normalized
      Cmin, Cmax, Caverage and area under the plasma concentration-time curve from 0 to
      the last measurable concentration (AUClast) showed negative correlations with the
      creatinine clearance. The combination of the 0 and 2-hour post-dose plasma
      concentrations was evaluated as the appropriate sampling point for TDM. Two
      patients reported nephrotoxic adverse events during colistin administration.
      CONCLUSIONS: Our study clarifies the PK characteristics of successful colistin
      treatment using TDM. Further evaluations in a larger patient population are
      needed to confirm the clinical usefulness of colistin TDM.

PMID- 30299431
TI  - Anti-Mullerian hormone as a predictor of reproductive potential.
AB  - PURPOSE OF REVIEW: Anti-Mullerian hormone (AMH), a marker of ovarian reserve,
      declines over a woman's reproductive lifespan. AMH is highly correlated with a
      woman's age and number of primordial ovarian follicles, and has been shown to
      predict time to menopause in women in their 40s. For these reasons, it was
      assumed that AMH levels could predict a woman's reproductive potential or serve
      as a 'fertility test'. Recently, studies have sought to determine the association
      between AMH and fertility. RECENT FINDINGS: Although a small, prospective, time
      to-pregnancy study of 98 women suggested that an AMH level less than 0.7 ng/ml
      was associated with lower day-specific probabilities of conception, the follow
      up, larger cohort did not identify an association with AMH and fecundability.
      Women with AMH values less than 0.7 ng/ml had similar pregnancy rates after 12
      cycles of attempting to conceive as women with normal AMH values after adjusting
      for age. Four additional studies, including a secondary analysis of the NICHD
      EAGER trial including over 1200 women confirmed these findings. SUMMARY: Although
      AMH is a marker of ovarian reserve, existing literature does not support the use
      of AMH as a marker of reproductive potential in the general population.

PMID- 30299432
TI  - Anti-mullerian hormone in the pathophysiology and diagnosis of polycystic ovarian
      syndrome.
AB  - PURPOSE OF REVIEW: Polycystic ovarian syndrome (PCOS) is the most common cause of
      chronic anovulation and hyperandrogenism in young women and represents a true
      public health concern and an economic burden. RECENT FINDINGS: The
      pathophysiology of PCOS is still not fully understood, but progresses have been
      made and the relationships between anti mullerian hormone (AMH), follicle
      stimulating hormone, luteinizing hormone, E2 and androgens have been explored.
      The follicle excess plays a central role in the syndrome and AMH is definitively
      a major component of this phenomena. SUMMARY: The aim of this chapter is to
      present the recent work studying the role of AMH in the pathophysiology of PCOS
      and to discuss the improvement that serum AMH assay brings in the diagnosis of
      PCOS.

PMID- 30299434
TI  - Current clinical applications of antimullerian hormone.
AB  - PURPOSE OF REVIEW: Determine if literature supports the use of anti-Mullerian
      hormone (AMH) as a useful biomarker of reproductive potential when cumulative
      live birth rates (CLBRs) per retrieval are used as the outcome variable. RECENT
      FINDINGS: Advances in technology used in in-vitro fertilization (IVF) permit the
      use of single embryo transfer to achieve expected pregnancy success rates. Many
      IVF cycles result in the creation of more than a single embryo suitable for
      transfer per oocyte retrieval. Cryopreservation permits subsequent use of other
      embryos with no loss in total reproductive potential from single retrievals.
      Therefore, an emerging concept in IVF is the CLBR per retrieval as an indicator
      of the patient's reproductive potential. Using the total reproductive potential
      from a single retrieval may help patients decide on IVF. As such, any predictor
      of success that relies upon the live birth rate for a single transfer, as opposed
      to CLBR per retrieval, is inadequate to estimate the true reproductive potential
      for patient. AMH has been proposed as a biomarker for reproductive potential, but
      most studies have correlated an AMH value to a single embryo transfer. SUMMARY: A
      more appropriate way to use AMH levels may be to correlate the AMH with CLBR per
      retrieval. AMH may thus prove to be a useful biomarker when counseling patients
      about what to expect from their treatment.

PMID- 30299433
TI  - The role of antimullerian hormone in assessing ovarian damage from chemotherapy,
      radiotherapy and surgery.
AB  - PURPOSE OF REVIEW: Iatrogenic ovarian damage can occur after chemotherapy,
      radiotherapy and surgery for cancer as well as for non-malignant conditions. This
      review describes the effects of such treatment on antimullerian hormone (AMH) and
      the implications of the fall in AMH in relation to ovarian function and
      fertility, especially in the era of improved fertility preservation strategies.
      RECENT FINDINGS: The risk of gonadotoxicity differs between chemotherapy
      regimens. There is growing evidence that pretreatment AMH has prognostic
      significance for the degree of fall in AMH after treatment, the reversibility of
      ovarian damage and risk of premature ovarian insufficiency. The accuracy of
      prediction increases when age is coupled with AMH. The adverse effect of removal
      of endometriomas is increasingly clear, and AMH pre and post surgery useful is
      assessing the degree of damage to the ovary. The implications of low AMH after
      such treatment on natural fertility and reproductive lifespan are less clear.
      Apart from treatment effects, there are other coexisting conditions that can
      affect AMH which needs to be taken into consideration during interpretation of
      AMH before and after treatment. SUMMARY: A fall in AMH in women after gonadotoxic
      treatment has been consistently described, with variable recovery, the accurate
      interpretation and clinical application of post-treatment AMH level on
      reproductive lifespan and fertility prediction needs to be studied in future
      larger prospective studies with longer follow-up.

PMID- 30299435
TI  - Use of bone turnover markers in the management of osteoporosis.
AB  - PURPOSE OF REVIEW: Osteoporosis is a common public health problem that is often
      undertreated and underdiagnosed. The clinical management of osteoporosis is often
      reactionary to devastating fracture events. Bone turnover markers may improve the
      ease and rapidity at which osteoporosis is monitored and treated. Bone turnover
      markers are biochemical byproducts of bone formation or bone resorption. The
      clinical use of bone turnover markers is limited by significant preanalytical
      variability. Effective interpretation of bone turnover markers requires a
      detailed understanding of the variables that can affect their responses to
      osteoporosis treatment and monitoring. RECENT FINDINGS: Progress is continuously
      being made on the standardization of bone turnover markers. The literature on the
      response of bone turnover markers to unique clinical situations is expanding.
      Data for evidence-based reference intervals for bone turnover markers has
      increased. Variables that affect the appropriate timing of lab draws like diurnal
      variation, postprandial status, exercise and alcohol use have been described.
      Studies examining the expected response of bone turnover markers to treatments of
      osteoporosis and other medications that affect bone health continue to increase.
      SUMMARY: Bone turnover markers have clinical utility in the comprehensive
      evaluation of osteoporosis. When interpreted with caution and with a good
      understanding of their natural variability, bone turnover markers provide
      information that supplements osteoporosis management and provides useful clinical
      information about conditions that alter bone turnover.

PMID- 30299436
TI  - [Evaluation of variety and quality in the school menus of Asturias. 2015/2016].
AB  - OBJECTIVE: Since the first evaluation in 2011 of the "Healthy Eating and
      Ecological Production Program in School Meals of Asturias", the improvement of
      the menus has been analyzed in terms of frequencies in the food group offer. The
      objective of this study was to evaluate the culinary quality of the menus, in
      order to complement this analysis. METHODS: Transversal descriptive study with a
      sample for convenience of the 243 Primary Education centers of Asturias, that is,
      195 in the 2015-16 academic year.. A monthly menu was requested to all the
      centers and in case of not receiving a response, a search was made on the
      Internet. Minimum criteria were defined to comply with frequencies, variety and
      recipes for each food group. The menus were analyzed every day and the
      differences between the menus cooked on site vs catering, as well as between
      public versus private / concerted centers. The data analysis was performed with
      the SPSS program and the differences between percentages of compliance with the
      Chi square test. RESULTS: 195 menus were analyzed (80.2%), obtaining high
      percentages of compliance in all the criteria (over 80%), except in the variety
      of carbohydrates (27.7%), fruit (22.1%). %), processed meat (13.9%), vegetable
      offer as first course (6.1%) and animal protein in the first course (2.6%).
      CONCLUSIONS: The general compliance of the recommendations with respect to
      variety and different recipes in the schools is very adequate, especially in
      those of public ownership and with own kitchen type.

PMID- 30299437
TI  - Corrigendum: Transcriptomic analyses of murine ventricular cardiomyocytes.
AB  - This corrects the article DOI: 10.1038/sdata.2018.170.

PMID- 30299438
TI  - Global-scale phylogenetic linguistic inference from lexical resources.
AB  - Automatic phylogenetic inference plays an increasingly important role in
      computational historical linguistics. Most pertinent work is currently based on
      expert cognate judgments. This limits the scope of this approach to a small
      number of well-studied language families. We used machine learning techniques to
      compile data suitable for phylogenetic inference from the ASJP database, a
      collection of almost 7,000 phonetically transcribed word lists over 40 concepts,
      covering two thirds of the extant world-wide linguistic diversity. First, we
      estimated Pointwise Mutual Information scores between sound classes using
      weighted sequence alignment and general-purpose optimization. From this we
      computed a dissimilarity matrix over all ASJP word lists. This matrix is suitable
      for distance-based phylogenetic inference. Second, we applied cognate clustering
      to the ASJP data, using supervised training of an SVM classifier on expert
      cognacy judgments. Third, we defined two types of binary characters, based on
      automatically inferred cognate classes and on sound-class occurrences. Several
      tests are reported demonstrating the suitability of these characters for
      character-based phylogenetic inference.

PMID- 30299439
TI  - An underwater observation dataset for fish classification and fishery assessment.
AB  - Using Dual-Frequency Identification Sonar (DIDSON), fishery acoustic observation
      data was collected from the Ocqueoc River, a tributary of Lake Huron in northern
      Michigan, USA. Data were collected March through July 2013 and 2016 and included
      the identification, via technology or expert analysis, of eight fish species as
      they passed through the DIDSON's field of view. A set of short DIDSON clips
      containing identified fish was curated. Additionally, two other datasets were
      created that include visualizations of the acoustic data and longer DIDSON clips.
      These datasets could complement future research characterizing the abundance and
      behavior of valued fishes such as walleye (Sander vitreus) or white sucker
      (Catostomus commersonii) or invasive fishes such as sea lamprey (Petromyzon
      marinus) or European carp (Cyprinus carpio). Given the abundance of DIDSON data
      and the fact that a portion of it is labeled, these data could aid in the
      creation of machine learning tools from DIDSON data, particularly for invasive
      sea lamprey which are amply represented and a destructive invader of the
      Laurentian Great Lakes.

PMID- 30299440
TI  - Corrigendum: High-throughput RNAi screen for essential genes and drug synergistic
      combinations in colorectal cancer.
AB  - This corrects the article DOI: 10.1038/sdata.2017.139.

PMID- 30299441
TI  - Isofraxidin targets the TLR4/MD-2 axis to prevent osteoarthritis development.
AB  - Osteoarthritis (OA) is a major cause of joint pain and disability, resulting in
      large socioeconomic costs worldwide. Isofraxidin (ISO), a bioactive coumarin
      compound isolated from the functional foods Siberian ginseng and Apium
      graveolens, exerts anti-inflammatory effects in a variety of diseases. However,
      no studies have reported the protective effects of ISO against OA development.
      Accordingly, this study aimed to assess the therapeutic effect of ISO in human OA
      chondrocytes, and in a mouse model of OA induced by destabilisation of the medial
      meniscus (DMM). In vitro, lipopolysaccharide (LPS)-induced overproduction of
      nitric oxide (NO), prostaglandin E2 (PGE2), tumour necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6) was decreased by ISO pre-treatment. Furthermore,
      ISO attenuated the increased expression of inflammatory enzymes, including
      inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in response
      to LPS stimulation. Meanwhile, LPS-induced extracellular matrix (ECM) degradation
      was also reversed by ISO treatment. Mechanistically, ISO competitively inhibited
      Toll-like receptor 4 (TLR4)/myeloid differentiation protein-2 (MD-2) complex
      formation, and thus TLR4/nuclear factor kappa B (NF-kappaB) signalling cascades.
      In vivo, ISO treatment not only prevented the calcification and erosion of
      cartilage, as well as the thickening of subchondral bone, but also reduced the
      serum levels of inflammatory cytokines in the mouse OA model. Taken together,
      these data suggest that ISO has potential in the treatment of OA.

PMID- 30299443
TI  - Tethered sensitizer-catalyst noble-metal-free molecular devices for solar-driven
      hydrogen generation.
AB  - Inspired by natural photosynthesis in an organized assembly, compact H2-evolving
      molecular devices, which tether sensitizer and catalyst modules in one single
      molecule, present an opportunity to overcome the diffusion limit required for
      multi-component molecular systems, and increase intramolecular electron transfer
      rates from the photoactivated unit to the catalytic center to improve H2-evolving
      efficiency. Thereinto absolutely noble-metal free H2-evolving molecular devices
      are of particular interest because they don't contain precious and scarce noble
      metal based components. This Frontier article focuses specifically on the recent
      advances in the design, synthesis, and photocatalytic properties of all-abundant
      element molecular devices for photoinduced H2 generation via intramolecular
      processes. Some challenges and suggestions for future directions in this field
      are also illustrated.

PMID- 30299444
TI  - Essential but sparse collagen hydroxylysyl post-translational modifications
      detected by DNP NMR.
AB  - The sparse but functionally essential post-translational collagen modification 5
      hydroxylysine can undergo further transformations, including crosslinking, O
      glycosylation, and glycation. Dynamic nuclear polarization (DNP) and stable
      isotope enriched lysine incorporation provide sufficient solid-state NMR
      sensitivity to identify these adducts directly in skin and vascular smooth muscle
      cell extracellular matrix (ECM), without extraction procedures, by comparison
      with chemical shifts of model compounds. Thus, DNP provides access to the
      elucidation of structural consequences of collagen modifications in intact
      tissue.

PMID- 30299446
TI  - Efficient synthesis of organic thioacetates in water.
AB  - Thioacetates as precursors of thiols are interesting starting points for
      synthesizing other organosulfur compounds. Herein, we propose a simple, efficient
      and fast method to obtain organic thioacetates using water as a solvent. Taking
      into account the great attention that has been paid toward environmentally
      friendly synthetic procedures in the past decades, we prove the role and the
      strength of the thioacetate anion as a nucleophile for nucleophilic displacement
      reactions in an aqueous medium. The reactions were carried out under pH control,
      to prevent the decomposition of the mesylate starting materials, using potassium
      carbonate as a safe and mild base. A simple work up allows products to be
      obtained with excellent yield and acceptable purity.

PMID- 30299450
TI  - Synergistic actions of mixed small and large pores for capillary absorption
      through biporous polymeric materials.
AB  - Water absorption in porous media is an important process involved in numerous
      materials for various applications, such as in the building industry, food
      processing and bioengineering. Designing new materials with appropriate
      absorption properties requires an understanding of how absorption behavior
      depends on both the material's morphology and the properties of the solid matrix,
      i.e. hydrophilic/hydrophobic nature and swelling/deformation properties. Although
      the basic principles of imbibition are well-known for simple porous systems, much
      less is known about absorption in complex porous systems, in particular those
      containing several coexisting porous phases, such as wood for example. Here,
      water absorption is studied for model porous organic materials exhibiting several
      degrees of hydrophobicity and two pore size levels, either as monoporous
      materials (large or small pores) or as biporous materials (mixed large and small
      pores). The interconnected biporous structure is designed via a double porogen
      templating approach using cubic sodium chloride particles as templates for the
      generation of the larger pore size (250-400 MUm) and i-PrOH as a porogenic
      solvent for the smaller pore size (2-5 MUm). While absorption for the small pore
      material is well described by the classical Washburn theory, the large pore
      material shows a drastic reduction in the imbibition rate. This behavior is
      attributed to the slow breakthrough mechanism for the water interface at sharp
      edge connections between pores. Remarkably, this slow regime is suppressed for
      the biporous material and the imbibition rate is even higher than the sum of
      rates obtained for its monoporous counterparts, which highlights the synergistic
      action of mixed small and large pores.

PMID- 30299451
TI  - Target Validity and the Hierarchy of Study Designs.
AB  - In recent years, increasing attention has been paid to problems of external
      validity, specifically to methodological approaches for both quantitative
      generalizability and transportability of study results. However, most approaches
      to these issues have considered external validity separately from internal
      validity. Here, we argue that considering either internal or external validity in
      isolation may be problematic. Further, we argue that a joint measure of the
      validity of an effect estimate with respect to a specific population of interest
      may be more useful: we call this proposed measure target validity. In this work,
      we introduce and formally define target validity as the total difference between
      the true causal effect in the target population and the estimated causal effect
      in the study sample. We illustrate this measure with a series of examples and
      show how this measure may help us to think more clearly about comparisons between
      experimental and non-experimental research results. Specifically, we show that
      even perfect internal validity does not ensure that a causal effect will be
      unbiased in a specific target population.

PMID- 30299452
TI  - Life expectancy with and without dementia: a population-based study of dementia
      burden and preventive potential.
AB  - Reliable population estimates of life-expectancy with dementia are required for
      shaping health care policy. 10,348 persons from the population-based Rotterdam
      Study were followed from 1990-2015 for dementia and death. We created multi-state
      lifetables, and assessed the effect of postponing disease onset. During 120,673
      person-years, 1,666 persons developed dementia, and 6,150 died. Overall life
      expectancy of women ranged from 18.0 years (95% confidence interval:17.8-18.2) at
      age 65 to 2.3 years (2.2-2.3) at age 95. Of total life-expectancy at age 65,
      5.7%, i.e. 1.0 year (1.0-1.1), was lived with dementia, increasing with age to
      42.1% (1.0 year,0.9-1.0) of life-expectancy at age 95. For men, overall life
      expectancy ranged from 15.6 years (15.4-15.9) at age 65 to 1.8 years (1.7-1.8) at
      age 95, of which 3.7% (0.6 year,0.5-0.6) and 35.3% (0.6 year,0.5-0.7) was lived
      with dementia, respectively. Postponing dementia onset by 1-3 years resulted in
      25-57% reductions in years lived with dementia. Survival after dementia diagnosis
      ranged from 6.7 (95%CI 5.3-8.1) years when diagnosed before age 70, to 2.6 years
      (2.3-2.9) >90 years. Dementia places a large burden on individuals and society in
      terms of healthy life-years lost, but this is potentially highly amendable by
      preventive interventions at the population level.

PMID- 30299453
TI  - Detection and prevention of adverse drug reactions in multi-morbid older
      patients.
AB  - Adverse drug reactions (ADRs) are a recognised unintentional form of iatrogenic
      harm, which commonly occur in older adults who have high levels of multi
      morbidity and associated polypharmacy. Previous studies estimate that at least
      one in 10 hospitalised older patients will experience an ADR. While recent
      research indicates that this could be as high as 39% in hospitalised multi
      morbid, older adults, up to two-thirds of these ADRs can be considered
      preventable and therefore potentially avoidable. In addition to increasing
      patient morbidity and contributing to avoidable mortality, there is an associated
      cost implication with ADR occurrence. This commentary summarises current
      mainstream research in terms of ADR detection, prediction and prevention in multi
      morbid older patients. At present, the biggest barrier to understanding and
      comparing ADRs in the literature is the large heterogeneity that exists in the
      population and study methods. Furthermore, there is the lack of standardised
      universally accepted methodology for ADR prediction, detection, causality
      assessment and subsequent prevention in older people. Standard available methods
      of ADR prediction applied to a heterogeneous multi-morbid population are
      generally unsatisfactory. Without an instrument that consistently and reliably
      predicts ADR risk in a reproducible manner, ADR prevention in multi-morbid older
      patients is challenging. Further attention should be focused on the culprit drugs
      that commonly lead to major ADRs in older multi-morbid hospitalised patients with
      polypharmacy. Risk associated with particular drug classes may possibly predict
      ADR occurrence better than patient characteristics alone. Current research is
      examining this drug class focus for ADR prevention in multi-morbid older people.

PMID- 30299454
TI  - Reductions in Cigarettes per Day and Mortality Among Older Adults in The United
      States.
AB  - Many smokers do not quit but instead reduce the number of cigarettes that they
      smoke per day (CPD) over their lifetime, yet the associations of such changes in
      CPD with health risks are unclear. We examined the association of changes in CPD
      with subsequent mortality (2004-2011) among 253,947 participants of the NIH-AARP
      Diet and Health Study. We identified cigarette smokers who quit, decreased,
      maintained, or increased their CPD between ages 25-29 and 50-59 using a
      questionnaire assessing smoking history in 2004-2005. Hazard ratios (HR) and 95%
      confidence intervals (CI) were from multivariable-adjusted Cox proportional
      hazards regression. Relative to never smokers, smokers who maintained a
      consistent CPD had 2.93 times (95%CI: 2.82, 3.05) higher all-cause mortality
      risk, with still higher risks observed in participants who increased their CPD
      (HR: 3.37, 95%CI: 3.23, 3.52). Risks were lower among participants who decreased
      their CPD (HR: 2.38, 95%CI: 2.25, 2.52) or quit smoking (HR for quitting between
      30-39 years: 1.32, 95%CI: 1.25, 1.39). Similar patterns were observed for smoking
      related causes of death, with particularly strong associations for lung cancer
      and respiratory disease. Reductions in CPD over the lifetime meaningfully
      decrease mortality risk. But cessation provides a larger benefit than even large
      declines in CPD.

PMID- 30299455
TI  - Letter to Editor: Long-Term Testosterone Administration on Insulin Sensitivity in
      Older Men with Low or Low-Normal Testosterone Levels.

PMID- 30299456
TI  - Host Preference and Olfaction in Drosophila mojavensis.
AB  - Many organisms live in complex environments that vary geographically in resource
      availability. This environmental heterogeneity can lead to changes within species
      in their phenotypic traits. For example, in many herbivorous insects, variation
      in host plant availability has been shown to influence insect host preference
      behavior. This behavior can be mediated in part through the insect olfactory
      system and the odor-evoked responses of olfactory receptor neurons (ORNs), which
      are in turn mediated by their corresponding odorant receptor genes. The desert
      dwelling fly Drosophila mojavensis is a model species for understanding the
      mechanisms underlying host preference in a heterogeneous environment. Depending
      on geographic region, one to multiple host plant species are available. Here, we
      conducted electrophysiological studies and found variation in responses of ORNs
      to host plant volatiles both within and between 2 populations-particularly to the
      odorant 4-methylphenol. Flies from select localities within each population were
      found to lack a response to 4-methylphenol. Experiments then assessed the extent
      to which these electrophysiological differences were associated with difference
      in several odor-mediated behavioral responses. No association between the
      presence/absence of these odor-evoked responses and short range olfactory
      behavior or oviposition behavior was observed. However, differences in odor
      induced feeding behavior in response to 4-methylphenol were found. Localities
      that exhibit an odor-evoked response to the odorant had increased feeding
      behavior in the presence of the odorant. This study sets the stage for future
      work examining the functional genetics underlying variation in odor perception.

PMID- 30299457
TI  - Reducing the Number of Unnecessary Thyroid Biopsies While Improving Diagnostic
      Accuracy: Toward the "Right" TIRADS.
AB  - Context: The prevalence of thyroid nodules in the general population is
      increasingly high, and at least half of those biopsied prove to be benign.
      Sonographic risk-stratification systems are being proposed as "rule-out" tests
      that can identify nodules that do not require fine-needle aspiration (FNA)
      cytology. Objective: To comparatively assess the performances of five
      internationally endorsed sonographic classification systems [those of the
      American Thyroid Association, the American Association of Clinical
      Endocrinologists, the American College of Radiology (ACR), the European Thyroid
      Association, and the Korean Society of Thyroid Radiology] in identifying nodules
      whose FNAs can be safely deferred and to estimate their negative predictive
      values (NPVs). Design: Prospective study of thyroid nodules referred for FNA.
      Setting: Single academic referral center. Patients: Four hundred seventy-seven
      patients (358 females, 75.2%); mean (SD) age, 55.9 (13.9) years. Main Outcome
      Measures: Number of biopsies classified as unnecessary, false-negative rate
      (FNR), sensitivity, specificity, predictive values, and diagnostic ORs for each
      system. Results: Application of the systems' FNA criteria would have reduced the
      number of biopsies performed by 17.1% to 53.4%. The ACR Thyroid Imaging Reporting
      and Data System (TIRADS) allowed the largest reduction (268 of 502) with the
      lowest FNR (NPV, 97.8%; 95% CI, 95.2% to 99.2%). Except for the Korean Society of
      Thyroid Radiology TIRADS, all other systems exhibited significant discriminatory
      performance but produced significantly smaller reductions in the number of
      procedures. Conclusions: Internationally endorsed sonographic risk stratification
      systems vary widely in their ability to reduce the number of unnecessary thyroid
      nodule FNAs. The ACR TIRADS outperformed the others, classifying more than half
      the biopsies as unnecessary with a FNR of 2.2%.

PMID- 30299458
TI  - Response to Letter "Long-Term Testosterone Administration on Insulin Sensitivity
      in Older Men with Low or Low-Normal Testosterone Levels".

PMID- 30299459
TI  - Impacts of various storage periods on egg quality, hatchability, post-hatching
      performance, and economic benefit analysis of two breeds of quail.
AB  - The effect of storage period on hatching and post-hatching performance of two
      quail breeds (brown Japanese quail (BJQ) and French white quail (FWQ)) was
      investigated using 940 eggs from each breed. Eggs were divided into four equal
      groups (235 eggs each), in each group. A total number of 210 eggs were used for
      incubation (with three replicates, 70 eggs each) and additional 25 eggs served as
      samples for egg quality parameters, each group was kept for special storage
      period. The first group was incubated on the same day of collection (zero day
      storage). Whereas the second, third, and fourth groups were stored for 4, 7, and
      10 d, respectively. Increasing the storage period more than 4 d significantly
      decreased the relative albumen weight, yolk index, total hatchability, and
      fertile eggs but significantly increased the relative yolk/albumen ratio,
      absolute and relative egg weight loss. Moreover, FWQ eggs exhibited higher (P <
      0.05) hatchability compared to BJQ eggs after 10 d of storage and yielded heavier
      chicks (P < 0.05) after all storage periods. The economic analysis indicated that
      the storage costs for FWQ eggs were significantly greater than those of BJQ at a
      0 d of storage (2.42 vs. 4.81 US cent (c); P < 0.05). Furthermore, the total
      costs for BJQ eggs were significantly lower than the total costs for FWQ eggs
      (3.0 vs. 7.0 c; P < 0.05). With respect to profitability, the total return
      represented by selling the chicks was calculated at 5.43 c for BJQ and 9.01 c for
      FWQ. The net return estimated for FWQ was significantly greater than that of BJQ
      (3.0 vs. 2.0 c; P < 0.05). However, the hatchability loss for FWQ was
      significantly greater than that of BJQ over different storage periods.

PMID- 30299460
TI  - Effects of dietary Zn-methionine supplementation on the laying performance, egg
      quality, antioxidant capacity, and serum parameters of laying hens.
AB  - This study was to determine the effects of dietary Zn-methionine (Zn-Met)
      supplementation on the laying performance, egg quality, antioxidant capacity, and
      serum parameters of laying hens. Jingh ong-1 strain laying hens (n = 720, 49 wk
      of age) were randomly assigned to 6 treatments with 6 replications of 20 birds.
      The control was fed a basal diet supplemented with 80 mg of Zn/kg as Zn sulphate
      of diet and the 5 groups were fed a basal diet supplemented with 20, 40, 60, 80,
      and 100 mg of Zn/kg as Zn-Met of diet for 10 wk, respectively. At the terminal
      experiment, there were significant differences between control and 80 mg/kg Zn
      Met group in feed intake (P < 0.05) and feed conversion ratio (FCR) (P < 0.01).
      Egg weight (P < 0.05) and albumen height (P < 0.01) reduced and were not
      significantly influenced by supplemental 80 mg/kg Zn-Met group until being stored
      15 d as compared to the control. Zn-Met group in 100 mg/kg significantly
      increased haugh unit (P < 0.05) as compared to the control. The activity of MDA
      in serum had a linear decrease in 20 to 100 mg/kg Zn-Met. The activity of CAT in
      liver and GSH-Px in serum had quadratic effects in response to the Zn-Met
      treatments. Compared to the control, 60 mg/kg Zn-Met group increased the T-AOC,
      GSH-Px activity in serum (P < 0.01), and the T-AOC (P < 0.05), CuZnSOD (P <
      0.01), GSH-Px (P < 0.01) activity in liver. Compared with the control, the
      concentration of serum ionic Ca in 80, 100 mg/kg Zn-Met treatments reduced (P <
      0.01) significantly while the activity of serum alkaline phosphatase (AKP)
      increased in the Zn-Met groups of 40, 60, and 80 mg/kg (P < 0.01), and 100 mg/kg
      (P < 0.05). In conclusion, dietary Zn-Met supplementation at 60 to 80 mg/kg had
      more positive effects on performance, egg quality, and antioxidant capacity in
      laying hens as compared to 80 mg/kg ZnSO4.

PMID- 30299461
TI  - Engineering of the upper hinge region of human IgG1 Fc enhances the binding
      affinity to FcgammaIIIa (CD16a) receptor isoform.
AB  - The interaction between antibodies and Immune cells surface FcgammaRIIIa (CD16a)
      receptor triggers a variety of immune responses including antibody-dependent cell
      mediated cytotoxicity, antibody neutralization, phagocytosis, inflammation and
      tissue injury. Recent studies showed that IgG1 upper hinge region and FcgammaRs
      polymorphism play a major role in the interaction with Fcgamma receptors and in
      the stability of the immune complex hence, in mounting strong inflammatory
      response. To further investigate this issue, we developed a tool box of IgG1 Fc
      isoforms to depict the affinity between mutated IgG1 Fc regions and extracellular
      domain variants (V158F) of CD16a. Our strategy consisted of designing different
      random upper-hinge mutated variants of IgG1 Fc domain, reproducing the naturally
      occurring two variants of CD16a and producing all of them as recombinant fusion
      proteins in Pichia Pastoris. The interactions were assayed using the Surface
      Plasmon Resonance (Biacore) method along with an in silico analysis to identify
      the major interaction and key residues that underline the affinity between the Fc
      region and CD16a variants. Our data showed that the affinity of the Fc region to
      the CD16a is strongly correlated to polar interactions. This molecular
      engineering approach yielded an IgG1Fc mutant with enhanced binding affinity to
      CD16a F158 variant.

PMID- 30299462
TI  - Assessing the effect of patient to provider language discordance on depression
      screening utilizing the Patient Health Questionnaire: an epidemiology study.
AB  - Background: As depression screening becomes a standard in primary care, the
      question remains of how effective and equitable screening can be implemented to
      avoid cultural and language-related disparities. Methods: In this retrospective
      cohort study, rates of depression screening were compared for 3626 adult patients
      at a family medicine residency-based health centre in Pennsylvania, USA. The PHQ
      2/PHQ-9 modality was verbally administered by nursing staff at the time of
      patient intake as part of a universal screening initiative. Chi-square analysis
      was used to determine the univariate associations of performed depression
      screening with variables of language, ethnicity, gender and number of office
      visits. A binary logistic regression was then performed to measure whether
      univariate associations remain significant after correction for other variables.
      Results: Chi-square analysis revealed significant differences in screening based
      on univariate associations of language, gender and number of office visits. No
      significant difference was found for age or ethnicity. Binary logistic regression
      revealed the following odds ratio of being screened for depression for each
      variable: Spanish language (OR = 0.694, CI = 0.559 to 0.862), female gender (OR =
      1.155, CI = 1.005 to 1.328) and office visit frequency of three or more office
      visits per year (OR = 2.103, CI = 1.835 to 2.410). Conclusions: Spanish-speaking
      adults were significantly less likely to be screened for depression than their
      English-speaking counterparts. Women were more likely to be screened than men,
      and the odds of screening increased with more frequent exposure to the office.
      Future studies should be directed at validating these findings in multiple
      clinical settings.

PMID- 30299463
TI  - Perceived Properties Are Not Free-Floating.

PMID- 30299464
TI  - Acute Effects of the Translocator Protein (TSPO) Drug Ligand FGIN-1-27 on Serum
      Testosterone and LH Levels in Male Sprague Dawley Rats.
AB  - We reported that FGIN-1-27 (N, N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide,
      FGIN), a synthetic ligand for translocator protein (TSPO, 18 kDa), increased
      serum testosterone levels in young and aged Brown Norway rats after its
      administration daily for 10 days. It is not known, however, how soon after
      treatment with FGIN serum testosterone rises, how long levels remain elevated
      after cessation of treatment, or whether the drug acts solely through TSPO. Adult
      Sprague Dawley male rats received a single ip dose of FGIN (1mg/kg BW). Serial
      blood samples were collected and serum testosterone and LH were assessed hourly
      throughout 24 hours. Testosterone concentration was maximal by 3 hours, remained
      significantly higher than the controls at 10 hours, and returned to the control
      level by 24 hours. Consistent with the in vivo study, culturing isolated Leydig
      cells with either FGIN (40MUM) or LH (0.1ng/ml) resulted in significantly
      increased testosterone production by 30 mins, and the stimulatory effects
      persisted through 48 hours. At a very early (15 min) treatment time, however,
      FGIN significantly increased testosterone production but LH had not yet done so.
      Surprisingly, in vivo treatment with FGIN not only increased serum testosterone
      but also serum LH concentration, raising the possibility that FGIN may increase
      serum testosterone concentration by dual mechanisms.

PMID- 30299465
TI  - Detected Objects, Perceived Properties.

PMID- 30299466
TI  - Seasonal variations in extracellular enzymatic activity in marine snow-associated
      microbial communities and their impact on the surrounding water.
AB  - Seasonal changes of microbial abundance and associated extracellular enzymatic
      activity in marine snow and in seawater were studied in the northern Adriatic
      during a three-year period. Marine snow was present during the entire period of
      investigation, although in higher concentrations during summer than during
      winter. Microorganisms densely colonized marine snow and aggregate-associated
      enzymatic activity was substantially higher (up to 105 times) than in seawater.
      Alkaline phosphatase activity (APA) and aminopeptidase activity in marine snow
      showed seasonal variations with higher values in late spring-summer than in
      autumn-winter, probably in response to changes in the quantity and quality of
      organic matter. The highest cell-specific bacterial activity was found for
      phosphatase, followed by peptidase, and the lowest was for glucosidases.
      Differential hydrolysis of marine snow-derived organic matter points to the well
      known phosphorus limitation of the northern Adriatic and indicates preferential
      utilization of phosphorus- and nitrogen-rich organic compounds by microbes, while
      hydrolysis of polysaccharides seemed to be less important. In oligotrophic
      conditions during summer, organic matter released from marine snow might
      represent a significant source of substrate for free-living bacteria in seawater.
      For the first time microorganisms producing APA in marine snow were identified,
      revealing that dense populations of bacteria expressed APA, while cyanobacteria
      did not. Cyanobacteria proliferating in marine snow could benefit from phosphorus
      release by bacteria and nanoflagellates.

PMID- 30299467
TI  - A dietary carbohydrase blend improved intestinal barrier function and growth rate
      in weaned pigs fed higher fiber diets.
AB  - The objective of this study was to evaluate the effects of dietary xylanase (X)
      and a carbohydrase enzyme blend (EB: cellulase, beta-glucanase, and xylanase) on
      nutrient digestibility, intestinal barrier integrity, inflammatory status, and
      growth performance in weaned piglets fed higher fiber diets. A total of 460 pigs
      (6.43 +/- 0.06 kg BW; F25 * 6.0 Genetiporc) were blocked by initial BW and pens
      (n = 12 per treatment) were randomly assigned to 1 of 4 dietary treatments. The
      diets included a higher fiber unsupplemented control diet (CON) and the CON
      supplemented with 0.01% X, 0.01% EB, or both enzymes, arranged in a 2 * 2
      factorial. The diets were based on corn, soybean meal, corn distillers dried
      grains with solubles (DDGS), and wheat middlings. Pigs had 7 d to adapt to the
      environment and consumed the same commercial diet. Pigs were fed the experimental
      diets for 28 d with free access to feed and water. Body weight and feed
      disappearance were recorded weekly. One pig with BW closest to the pen average
      from each pen was selected and moved to metabolism crates on day 16 and
      intragastric gavaged a solution of lactulose and mannitol on day 22 followed by
      12-h urine collection. Feces were collected from day 23 to 25. Intestinal tissues
      and mucosal scrapings were collected on day 28. Data were analyzed using PROC
      MIXED of SAS (9.4). Xylanase, EB, and their interaction were fixed effects and
      block was a random effect. The EB, but not X, increased pig BW and improved ADG
      over 28 d (P < 0.05). Neither carbohydrase impacted ADFI, G:F, or apparent total
      tract digestibility (ATTD) of DM, GE, or CP. The EB improved ATTD of ADF (32.45
      vs. 26.57%; P < 0.01), but had no effect on NDF. Unexpectedly, X reduced ATTD of
      NDF and ADF (P < 0.01). The EB reduced urinary lactulose:mannitol and increased
      ileal claudin-3 mRNA abundance (P < 0.05), indicating improved small intestinal
      barrier integrity. There was a X * EB interaction on ileal secretory
      immunoglobulin A (sIgA) concentration (P < 0.05); in the absence of X, EB
      decreased sIgA compared to CON, but this effect disappeared in the presence of X.
      The EB also reduced ileal IL-22 mRNA abundance (P < 0.05), probably indicating
      decreased immune activation. In conclusion, EB but not X enhanced growth rate of
      weaned pigs fed higher fiber diets, which may be partly explained by the improved
      small intestinal barrier integrity and reduced immune activation, rather than
      improvement in nutrient digestibility.

PMID- 30299469
TI  - Effect of familiarity and mixing method on gestating sow welfare and productivity
      in large dynamic groups.
AB  - The objectives of this study were twofold: first, to investigate the effects of
      sow familiarity prior to mixing into a larger dynamic group of gestating sows
      and, second, to examine the impact of how the sows entered the pen during this
      mixing event. The cohort of sows was either familiar with each other because of
      premixing (PMIX) or unfamiliar (UMIX). This PMIX or containment of sows in a
      stall (UMIX), occurred from weaning until the sows were mixed into the large
      gestation pen 8 d later. The cohort of incoming sows was introduced either as a
      batched unit (BAT) or new sows were introduced into the dynamic group singly
      (IND) though the electronic sow feeder. Lesion severity and quantity score,
      lameness, and body condition score (BCS) were tracked throughout the entire
      gestation period for 213 sows. Overall, there was little effect of the treatment
      but a strong impact of parity on the outcomes. Younger animals had significantly
      higher risk for lesions (P < 0.001) and higher risk for more severe lesions (P <
      0.001) than higher parity animals. Lower parity had an association with the risk
      of lameness (P < 0.05), but it had no significant effect on BCS (P > 0.05). The
      risk of lameness increased on days 15 and 62 compared to weaning (P < 0.001).
      Risk of low BCS decreased on days 62 and 113 relative to scores at weaning (P <
      0.001). A degree of familiarity by day interaction was present for lesion
      quantity (P < 0.001) and lesion severity (P < 0.001). The risk of more lesions
      was higher in the premixed groups before going into the dynamic group, but
      equilibrated with the unmixed group after day 11, 3 d in the large dynamic pen.
      The highest risk for the greatest quantity of lesions peaked at day 11 then
      declined, but never reached the lowest level again which was measured at weaning.
      Despite the variability in the welfare measures, there was no significant impact
      of treatment or parity on sow productivity. In conclusion, our data demonstrate
      that a period of premixing sows and varying the method of entering sows into the
      pen did not have a long-term impact on the welfare of the sows or on their
      productivity.

PMID- 30299468
TI  - Prevalence and risk factors of zygotic splitting after 937 848 single embryo
      transfer cycles.
AB  - STUDY QUESTION: What is the prevalence of multiple pregnancy with zygotic
      splitting after single embryo transfer (SET)? SUMMARY ANSWER: The prevalence of
      multiple pregnancy with zygotic splitting after SET was 1.36%. WHAT IS KNOWN
      ALREADY: In 2008, the Japan Society of Obstetrics and Gynaecology (JSOG)
      recommended the adoption of SET to reduce multiple births. Since then, to improve
      the clinical pregnancy rate, elective SET using blastocyst transfer and frozen
      warmed ET has increased. Blastocyst culture and zona pellucida manipulation,
      including ICSI and AH, have been widely reported as risk factors for monozygotic
      twinning. However, all these studies may have included cases with dizygotic
      pregnancies produced by a transferred embryo and a spontaneous conception. STUDY
      DESIGN, SIZE, DURATION: A retrospective observational study was performed, based
      on 937 848 SET cycles in registered ART data from the JSOG between 2007 and 2014.
      The study was approved by the Registration and Research Subcommittee of the JSOG
      and Juntendo University Ethics Committee. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: To identify possible factors affecting the prevalence of zygotic
      splitting, we identified pregnancies, in which the number of foetuses exceeded
      the number of gestational sacs (GSs), to restrict our analysis to 'true' zygotic
      splitting. Multiple logistic regression analysis was performed using singleton
      pregnancy after SET, as control. P < 0.05 was considered statistically
      significant. MAIN RESULTS AND THE ROLE OF CHANCE: Fresh and frozen-warmed SET
      produced 276 934 clinical pregnancies (29.5%/SET), including 4310 twins (1.56% of
      pregnancies) and 109 triplets (0.04% of pregnancies). Based on sex analysis of
      dichorionic twins after SET, the prevalence of multiple pregnancy with zygotic
      splitting was 1.36%. Statistical analysis revealed that compared to singleton
      pregnancies zygotic splitting pregnancies were associated with frozen-warmed ET
      cycles (odds ratio [OR] = 1.34; 95% CI: 1.16-1.55), blastocyst culture (OR =
      1.79; 95% CI: 1.54-2.09) or AH (OR = 1.21; 95% CI: 1.08-1.35). In fresh ET
      cycles, the prevalence rate of zygotic splitting pregnancy after single
      blastocyst transfer was significantly higher than that after SET cycles with
      cleavage embryos (OR = 2.20; 95% CI: 1.83-2.66). However, no significant
      difference in ovarian stimulation and fertilization methods was recognized.
      LIMITATIONS, REASONS FOR CAUTION: In the current Japanese ART registry system,
      data regarding frozen-warmed ET do not include information about ovarian
      stimulation and fertilization methods. Registration for AH only began in 2010.
      There is no way of validating if data submitted by clinics is correct. WIDER
      IMPLICATIONS OF THE FINDINGS: Clinicians should consider whether to counsel
      couples about the small increase in the risk of zygotic splitting associated with
      some embryo manipulations. STUDY FUNDING/COMPETING INTEREST(S): No external funds
      were used for the study. The authors have no competing interests to declare.
      TRIAL REGISTRATION NUMBER: None.

PMID- 30299470
TI  - Kit-independent mast cell adhesion mediated by Notch.
AB  - Kit/CD117 plays a crucial role in the cell-cell and cell-matrix adhesion of
      mammalian mast cells (MCs); however, it is unclear whether other adhesion
      molecule(s) perform important roles in the adhesion of MCs. In the present study,
      we show a novel Kit-independent adhesion mechanism of mouse cultured MCs mediated
      by Notch family members. On stromal cells transduced with each Notch ligand gene,
      Kit and its signaling become dispensable for the entire adhesion process of MCs
      from tethering to spreading. The Notch-mediated spreading of adherent MCs
      involves the activation of phosphatidylinositol 3-kinases and mitogen-activated
      protein kinases signaling, similar to Kit-mediated spreading. Despite the
      activation of the same signaling pathways, while Kit supports the adhesion and
      survival of MCs, Notch only supports adhesion. Thus, Notch family members are
      specialized adhesion molecules for MCs that effectively replace the adhesion
      function of Kit in order to support the interaction of MCs with the surrounding
      cellular microenvironments.

PMID- 30299471
TI  - Streptomyces protein secretion and its application in biotechnology.
AB  - Bacteria are of tremendous importance in the pharma- and bio-industry as
      producers of a broad range of economically interesting metabolites and proteins.
      Gram-positive bacteria are valuable hosts for the production of heterologous
      proteins for obvious reasons. Contrary to Gram-negative bacteria, Gram-positive
      bacteria release their secreted proteins immediately into the spent culture broth
      as they are not hindered by an outer membrane. Secretory protein production also
      avoids the formation of inclusion bodies, hence facilitating downstream
      processing. Eight protein secretion pathways have been described in Gram-positive
      bacteria, but solely the general secretion or Sec pathway and, to a lesser
      extent, the Twin-arginine pathway, are used for the recombinant protein
      production. This process is not always successful, but might be hampered by
      inefficient secretion, misfolding of the recombinant protein, its degradation by
      proteases and metabolic burden by the host hindering proper growth and
      diminishing product yield. In this review, the different protein export avenues
      will be briefly discussed, and the potential means to optimize protein secretion
      and yields for the Streptomyces lividans model presented. The proposed approaches
      are largely applicable for other Streptomyces host systems.

PMID- 30299472
TI  - Use of Soil and Litter Ants (Hymenoptera: Formicidae) as Biological Indicators of
      Soil Quality Under Different Land Uses in Southern Rwanda.
AB  - The use of soil and litter arthropods as biological indicators is a way to assess
      environmental changes, where ant species in particular may serve as important
      indicators of soil quality. This study aimed at relating the abundance of soil
      and litter ant species to soil parameters under different tree species, both
      native and exotic, and varieties of coffee and banana plantations. Variations
      were found in soil physicochemical parameters. A total of 30 species belonging to
      14 genera, and four subfamilies, the Formicinae, Dorylinae, Myrmicinae, and
      Ponerinae were identified. Higher abundance was found in coffee plantations
      compared to banana plantations, exotic and native tree species. Species of
      Camponotus cinctellus and Odontomachus troglodytes occurred in all land uses
      which is a sign of tolerance to a wide range of soil properties. In addition,
      these species, together with Myrmicaria SP02, Phrynoponera gabonensis, Camponotus
      SP06, Myrmicaria opaciventris, Pheidole SP03, Tetramorium simillimum, Pheidole
      SP01, and Tetramorium laevithorax were not strongly correlated with soil
      physicochemical parameters. Species of Pheidole SP02 and Camponotus SP05 were
      restricted to specific soil physicochemical properties, while species of
      Tetramorium zonacaciae and Bothroponera talpa discriminated between native tree
      species, coffee plantations, soil organic carbon, sandy soil texture, and
      aggregate stability. We concluded that these ant species can differently indicate
      the soil quality depending on the land use. We recommended further studies in
      order to generalize these findings.

PMID- 30299473
TI  - Statin treatment decreases mitochondrial respiration but muscle coenzyme Q10
      levels are unaltered: The LIFESTAT study.
AB  - Background: Myalgia is a common side effect to statin therapy, but the underlying
      mechanism is unknown. Statins may reduce Coenzyme Q10 (CoQ10) which is an
      essential electron carrier in the mitochondrial electron transport system,
      thereby impairing mitochondrial respiratory function potential leading to
      myalgia. Objectives: To investigate whether statin induced myalgia is coupled to
      reduced intramuscular CoQ10 concentration and impaired mitochondrial respiratory
      function. Methods: 64 men and women in simvastatin therapy were recruited. 25 who
      experienced myalgia were allocated to the myalgic group. The remaining 39 statin
      users had no symptoms of myalgia (non-sympt). 20 men and women with untreated
      high blood cholesterol levels were recruited as control group. Blood and muscle
      samples were obtained. Intramuscular CoQ10 concentration was measured, and
      mitochondrial respiratory function and reactive oxygen species (ROS) production
      were measured. Citrate Synthase (CS) activity was used as a biomarker for
      mitochondrial content in skeletal muscle. Results: Intramuscular CoQ10
      concentration was comparable between groups. Mitochondrial complex II-linked
      respiration was reduced in the statin myalgic and statin non-symptomatic groups
      compared to control. When mitochondrial respiration was normalized to CS activity
      respiration rate was higher in the myalgic group compared to non-symptomatic and
      control group. Maximal ROS production was similar between groups. Discussion: Our
      results suggests that statin therapy impairs mitochondrial complex-II linked
      respiration, but the mitochondrial capacity for complex I+II linked respiration
      is intact. Myalgia is not coupled to reduced intramuscular CoQ10 levels.
      Intrinsic mitochondrial respiratory capacity is increased with statin induced
      myalgia, but not accompanied by increased ROS production.

PMID- 30299474
TI  - Friends or foes in the rhizosphere: traits of fluorescent Pseudomonas that hinder
      Azospirillum brasilense growth and root colonization.
AB  - Bacteria of the Azospirillum and Pseudomonas genera are ubiquitous members of the
      rhizosphere, where they stimulate plant growth. Given the outstanding capacity of
      pseudomonads to antagonize other microorganisms, we analyzed the interaction
      between these two bacterial groups to identify determinants of their
      compatibility. We could establish that, when in direct contact, certain
      Pseudomonas strains produce lethality on Azospirillum brasilense cells using an
      antibacterial type 6 secretion system. When analyzing the effect of Pseudomonas
      spp. diffusible metabolites on A. brasilense growth on King's B medium, we
      detected strong inhibitory effects, mostly mediated by siderophores. On Congo Red
      medium, both inhibitory and stimulatory effects were induced by unidentified
      compounds. Under this condition, Pseudomonas protegens CHA0 produced a Gac/Rsm
      regulated antibiotic which specifically inhibited A. brasilense Sp7 but not
      Sp245. This effect was not associated with the production of 2,4
      diacetylphloroglucinol. The three identified antagonism determinants were also
      active in vivo, producing a reduction of viable cells of A. brasilense in the
      roots of wheat seedlings when co-inoculated with pseudomonads. These results are
      relevant to the understanding of social dynamics in the rhizosphere and might aid
      in the selection of strains for mixed inoculants.

PMID- 30299475
TI  - Evaluation of Escherichia coli pathotypes associated with irritable bowel
      syndrome.
AB  - Irritable bowel syndrome (IBS) affects 10%-20% of people. Increased numbers of
      Escherichia coli (E. coli) correlate with symptoms, and patients respond to
      antimicrobials targeting E. coli. We examined whether specific E. coli strains,
      phylogroups and pathotypes are associated with IBS. We evaluated 218 E. coli
      isolates from 33 IBS patients and 23 healthy controls. RAPD analysis revealed 89
      E. coli strains (29 controls, 60 IBS), spanning the A, B1, B2 and D phylogroups.
      Strains were similarly enriched in virulence genes associated with
      extraintestinal pathogenic E. coli (ExPEC) and/or adherent-invasive E. coli
      (AIEC). Three strains harbored a diarrheagenic virulence gene (2 IBS, 1 control).
      Escherichia coli capable of invading epithelial cells or replicating in
      macrophages were detected in 53% of IBS and 50% controls, and 67% IBS and 45%
      controls respectively (P > 0.05). AIEC were identified in 33% of IBS patients vs
      20% of controls (P = 0.35). Virulence genes ibeA, ColV and pduC were associated
      with intramacrophage persistence; ibeA and ColV were associated with epithelial
      invasion and AIEC pathotype (P < 0.05). IBS patients and controls are commonly
      colonized by E. coli that resemble ExPEC and display pathogen-like behavior in
      vitro, similar to CD-associated AIEC. The relationship of these resident
      pathosymbiont E. coli to IBS warrants further investigation.

PMID- 30299476
TI  - Quantitative proteomic analysis of xylose fermentation strain Pichia stipitis CBS
      5776 to lignocellulosic inhibitors acetic acid, vanillin and 5
      hydroxymethylfurfural.
AB  - To obtain a global insight into the dynamic protein expression pattern in Pichia
      stipitis during xylose fermentation in the presence of three representative
      inhibitors (acetic acid, vanillin and 5-hydroxymethylfurfural), proteins were
      extracted for quantitative proteomic analysis using 8-plex isobaric tag for
      relative and absolute quantitation (iTRAQ) on a liquid chromatography-mass/mass
      spectrometry instrument. Interestingly, aconitase (Aco1p) and NAD-isocitrate
      dehydrogenase (Idh1p) were upregulated during the middle exponential phase in the
      presence of the three inhibitors during tricarboxylic acid cycle. We speculated
      that yeast cells adaptively increased the expression of the tricarboxylic acid
      cycle proteins to compensate for low NADH derived from glycolysis in the presence
      of the three inhibitors. Proteins related to amino acid metabolism, aminoacyl
      tRNA synthesis and stress response were also significantly affected in the
      presence of the three inhibitors. Taken together, quantitative proteomic analysis
      is capable of monitoring P. stipitis xylose fermentation under inhibitor
      conditions and identifying physiological changes, such as stress response.

PMID- 30299477
TI  - eAssessment: development of an electronic version of the Objective Structured
      Assessment of Debriefing tool to streamline evaluation of video recorded
      debriefings.
AB  - Objective: The Objective Structured Assessment of Debriefing (OSAD) is an
      evidence-based, 8-item tool that uses a behaviorally anchored rating scale in
      paper-based form to evaluate the quality of debriefing in medical education. The
      objective of this project was twofold: 1) to create an easy-to-use electronic
      format of the OSAD (eOSAD) in order to streamline data entry; and 2) to pilot its
      use on videoed debriefings. Materials and Methods: The eOSAD was developed in
      collaboration with the LSU Health New Orleans Epidemiology Data Center using
      SurveyGizmo (Widgix Software, LLC, Boulder, CO, USA) software. The eOSAD was then
      piloted by 2 trained evaluators who rated 37 videos of faculty teams conducting
      pre-briefing and debriefing after a high-fidelity trauma simulation. Inter-rater
      reliability was assessed, and evaluators' qualitative feedback was obtained.
      Results: Inter-rater reliability was good [prebrief, intraclass correlation
      coefficient, ICC = 0.955 (95% CI, 0.912-0.977), P < .001; debrief, ICC = 0.853
      (95% CI, 0.713-0.924), P < .001]. Qualitative feedback from evaluators found that
      the eOSAD was easy to complete, simple to read and add comments, and reliably
      stored data that were readily retrievable, enabling the smooth dissemination of
      information collected. Discussion: The eOSAD features a secure login, sharable
      internet access link for distant evaluators, and the immediate exporting of data
      into a secure database for future analysis. It provided convenience for end
      users, produced reliable assessments among independent evaluators, and eliminated
      multiple sources of possible data corruption. Conclusion: The eOSAD tool format
      advances the post debriefing evaluation of videoed inter-professional team
      training in high-fidelity simulation.

PMID- 30299478
TI  - A simple mathematical model to describe antibody-dependent enhancement in
      heterologous secondary infection in dengue.
AB  - We develop a mathematical model to describe the role of antibody-dependent
      enhancement (ADE) in heterologous secondary infections, assuming that antibodies
      specific to primary dengue virus (DENV) infection are being produced by
      immunological memory. The model has a virus-free equilibrium (VFE) and a unique
      virus-presence equilibrium (VPE). VFE is asymptotically stable when VPE is
      unstable; and unstable, otherwise. Additionally, there is an asymptotic attractor
      (not a fixed point) due to the fact that the model assumes unbounded increase in
      memory cells. In the analysis of the model, ADE must be accounted in the initial
      stage of infection (a window of time of few days), period of time elapsed from
      the heterologous infection until the immune system mounting an effective response
      against the secondary infection. We apply the results yielded by model to
      evaluate ADE phenomonon in heterologous DENV infection. We also associate the
      possible occurrence of severe dengue with huge viremia mediated by ADE
      phenomenon.

PMID- 30299479
TI  - Cross-sectional associations between body mass index and social-emotional
      wellbeing among differentially active children.
AB  - Background: This study assessed gender-specific associations between body mass
      index (BMI) and social-emotional wellbeing (SEW) among differentially active
      seven-year-old children. Methods: Data are from wave four of the UK Millennium
      Cohort Study, collected in 2007-08. Children wore an ActiGraph accelerometer for
      seven consecutive days and measures of stature and body mass were taken. BMI was
      calculated from stature and body mass (kg/m2). Parents/carers completed the
      strengths and difficulties questionnaire (SDQ). A total of 6011 children (3073
      girls) had completed data. Mean minutes per day spent in moderate-to-vigorous
      intensity physical activity (MVPA) were calculated for each child. Gender
      specific MVPA quartile cut-off values categorized boys and girls separately into
      four graded groups representing the least (Q1) through to the most active (Q4)
      children. Adjusted linear regression analyses examined associations between BMI
      and SDQ scores. Gender-specific analyses were conducted separately for MVPA
      quartiles. Results: BMI was positively associated with peer problems for Q1 and
      Q2 boys and girls, conduct problems for Q2 and Q4 boys, emotional problems and
      prosocial behaviour for Q2 boys and total difficulty scores for Q1 girls and Q2
      boys (P < 0.05). Conclusions: Our results revealed that BMI was positively
      associated with SEW difficulties among the low active children but not the high
      active children. Further research examining the concurrent effect of diet and
      MVPA on child weight status and SEW is needed.

PMID- 30299480
TI  - Characterization of the CYP11A1 Non-synonymous Variant p.E314K in Children
      Presenting with Adrenal Insufficiency.
AB  - Context: Cholesterol side-chain cleavage enzyme (P450scc), encoded by CYP11A1
      catalyzes the first step of steroidogenesis. Complete P450scc deficiency leads to
      primary adrenal insufficiency (PAI) and 46,XY disordered sexual development.
      Partial impairment can cause variable adrenal and gonadal dysfunction. Objective:
      Our aim was to evaluate the effects of the CYP11A1 variant p.E314K, identified in
      patients with PAI, specifically on P450scc enzyme stability and function.
      Patients/Methods: We studied four males from two unrelated families presenting
      with PAI during childhood (3.6 to 9 years old). All patients were compound
      heterozygous for c.940G>A (p.E314K), a CYP11A1 non-synonymous variant likely to
      be pathogenic by some but not all in silico prediction models, and c.835delA
      (p.I79Yfs*10), a known pathogenic variant. HEK293T cells were transfected with
      wild-type (WT) and p.E314K mutant vectors, and a cycloheximide chase assay was
      performed to analyze protein stability. Pregnenolone production was assayed from
      cells expressing WT and p.E314K-F2 fusion proteins. Results: Two males
      experienced spontaneous puberty, but then developed evidence of primary gonadal
      failure at 14 and 18 years old. Two males had testicular adrenal rest tissue
      (TART), detected by ultrasound at ages 8.6 and 16 years. Compared to WT, mutant
      protein synthesis was reduced (P=0.0006) with increased protein turn over, and
      mutant P450scc half-life was decreased by approximately 50%. p.E314K mutant
      P450scc retained 60% of WT enzymatic activity (P=0.007). Conclusions: The CYP11A1
      p.E314K variant impairs P450scc stability and is a possible cause of PAI during
      childhood. Pathogenic CYP11A1 variants potentially impact both adrenal and
      gonadal function and males may develop TART.

PMID- 30299481
TI  - How Clean Is the Linen at My Hospital? The Mucorales on Unclean Linen Discovery
      Study of Large United States Transplant and Cancer Centers.
AB  - Mucormycosis outbreaks have been linked to contaminated linen. We performed
      fungal cultures on freshly-laundered linens at 15 transplant and cancer
      hospitals. At 33% of hospitals, the linens were visibly unclean. At 20%,
      Mucorales were recovered from >10% of linens. Studies are needed to understand
      the clinical significance of our findings.

PMID- 30299483
TI  - Sex influences SAMHD1 activity and susceptibility to HIV-1 in primary human
      macrophages.
AB  - While it is known that host sex affects HIV-1 viremia and influences the severity
      of HIV-1 associated neurocognitive disease, a cellular or molecular basis for
      these findings remains elusive. Macrophages are major targets for HIV-1,
      contribute to viral propagation in vivo, and are instrumental in the pathogenesis
      of HAND. We explored whether sex affects HIV-1 infectivity of primary human
      macrophages and CD4+ T cells in vitro. We find that macrophages derived from
      female donors were less susceptible to HIV-1 infection than those derived from
      males. This sex-dependent difference in macrophage infectivity was independent of
      the requirement for CD4/CCR5-mediated virus entry and was not observed in CD4+ T
      cells. Investigations into the mechanism governing these sex-dependent
      differences revealed that the host restriction factor SAMHD1 exists in a
      hyperphosphorylated, less active state in male-derived macrophages. In addition,
      the major kinase responsible for SAMHD1 phosphorylation, CDK1, exhibited lower
      levels of expression in female-derived macrophages in all tested donor pairs. The
      sex-dependent differences in viral restriction imposed by SAMHD1 were abrogated
      upon its depletion. We conclude that SAMHD1 is an essential modulator of
      infectivity in a sex-dependent manner in macrophages, constituting a novel
      component of sex differences in innate immune control of HIV-1.

PMID- 30299482
TI  - Assessment of ovarian reserve after cystectomy versus 'one-step' laser
      vaporization in the treatment of ovarian endometrioma: a small randomized
      clinical trial.
AB  - STUDY QUESTION: Does CO2 laser vaporization offer better results in treating
      endometrioma in terms of ovarian reserve preservation compared to traditional
      cystectomy? SUMMARY ANSWER: Assessing both antral follicle count (AFC) and serum
      anti-Mullerian hormone (AMH) levels as measures of ovarian reserve, the results
      suggest that CO2 technology may be an alternative treatment for endometrioma,
      causing minimal damage to adjacent healthy ovarian tissue. WHAT IS KNOWN ALREADY:
      Excisional surgery has been questioned as an ideal surgical approach for
      endometriomas because it is associated with potential reduction of ovarian
      reserve. Recently, vaporization with CO2 laser in-line-of-sight, according to the
      'three-step procedure', has been proposed as the best method to preserve ovarian
      function. However, no randomized controlled trials have been conducted to compare
      cystectomy and 'one-step' CO2 fiber laser vaporization (without GnRH agonist
      therapy) with respect to the ovarian reserve. STUDY DESIGN, SIZE, DURATION: A
      multicentre randomized clinical trial including 60 patients was performed between
      July 2017 and February 2018. Computerized randomization was conducted to allocate
      them in a proportion of 1:1 either to Group 1 (laparoscopic stripping:
      cystectomy) or Group 2 (CO2 laser vaporization). Patients in Group 1 underwent a
      standardized laparoscopic stripping technique; patients in Group 2 underwent
      drainage of the cyst content, biopsy and vaporization of the internal wall with a
      CO2 fiber laser. Patients underwent pelvic ultrasound examination to determine
      the AFC and blood sampling to determine AMH levels before surgery and at 1- and 3
      month follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients undergoing
      surgery for symptomatic endometriomas (infertility and/or pelvic pain) larger
      than 3 cm were randomized in two groups according to the surgical technique.
      Patients aged >=40 years, or with deep infiltrating endometriosis/adenomyosis, or
      previously submitted to surgical procedures on the ovaries or to hysterectomy
      were excluded from the study. The primary endpoint was the comparison of intra
      group AFC changes before and after surgery (DeltaAFC) between the two groups
      (DeltaAFC Group 1 versus DeltaAFC Group 2). The secondary endpoint was the
      modification of serum AMH before and after surgery (DeltaAMH) between the two
      groups (DeltaAMH Group 1 versus DeltaAMH Group 2). MAIN RESULTS AND THE ROLE OF
      CHANCE: The AFC of the operated ovary was significantly increased in Group 2
      (laser vaporization) compared with Group 1 (cystectomy) after surgery (Group 1:
      from 4.1 +/- 2.2 [mean +/- SD] at baseline to 6.3 +/- 3.5 at 3-month follow-up;
      95% CI: 0.9-4; Group 2: from 3.6 +/- 1.9 at baseline to 8.6 +/- 4.2 at 3-month
      follow-up; 95% CI: 2.8-7.1; P = 0.016); serum AMH levels were significantly
      reduced at 3 months in Group 1 (from 2.6 +/- 1.4 ng/mL at baseline to 1.8 +/- 0.8
      ng/mL at 3-month follow-up; 95% CI: -1.3 to -0.2; P = 0.012) compared with no
      reduction in Group 2 (from 2.3 +/- 1.1 ng/mL at baseline to 1.9 +/- 0.9 ng/mL at
      3-month follow-up; 95% CI: -1 to -0.2; P = 0.09). LIMITATIONS, REASON FOR
      CAUTION: The key limitations of the trial were the low accuracy of AFC in
      estimating the ovarian reserve in ovaries with endometriomas, the limited study
      size and the relatively short follow-up, which do not allow us to draw definitive
      conclusions. WIDER IMPLICATIONS OF THE FINDINGS: The present study suggests that
      CO2 technology may treat endometrioma with minimal damage to the adjacent healthy
      ovarian tissue; however, this study should be considered as a preliminary
      clinical trial, intended to stimulate future larger trials to address this
      clinically relevant issue. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL
      REGISTRATION NUMBER: ClinicalTrials.gov NCT03227640. TRIAL REGISTRATION DATE: 9
      July 2017. DATE OF FIRST PATIENT'S ENROLLMENT: 24 July 2017.

PMID- 30299484
TI  - Steroid-Responsive Relapsing-Remitting Neutrophilic Encephalitis: A Case Report.
AB  - We report a case of a rapidly progressing, relapsing-remitting, steroid
      responsive granulocytic encephalitis without any signs of peripheral nervous
      system or other organ involvement. It apparently had an immune-mediated etiology
      that could not be attributed to any known disease entity. A 22-year-old man
      presented with rapidly progressive severe neurological symptoms caused by
      encephalitis. Examination of the cerebrospinal fluid as well as brain biopsy
      showed extensive accumulation of neutrophilic granulocytes with no hints of an
      infectious agent. Magnetic resonance imaging revealed multiple T2/FLAIR
      demarcated lesions. Subsequent to a steroid pulse therapy, the clinical symptoms
      and imaging abnormalities improved rapidly. Ten months later, the patient
      experienced a disease relapse, which again responded well to steroids. Forty
      months after the relapse, he is currently doing well on azathioprine. This case
      highlights that an immunosuppressive treatment should be considered in patients
      with extensive neutrophilic encephalitis when no infectious agent is detected. A
      new immune-mediated relapsing-remitting CNS disease entity might need to be
      considered.

PMID- 30299486
TI  - Global Health and the Infectious Diseases Physician-Scientist Workforce.

PMID- 30299485
TI  - Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines
      on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma:
      Novel Surgical Strategies.
AB  - BACKGROUND: Treatment of thoracolumbar burst fractures has traditionally involved
      spinal instrumentation with fusion performed with standard open surgical
      techniques. Novel surgical strategies, including instrumentation without fusion
      and percutaneous instrumentation alone, have been considered less invasive and
      more efficient treatments. OBJECTIVE: To review the current literature and
      determine the role of fusion in instrumented fixation, as well as the role of
      percutaneous instrumentation, in the treatment of patients with thoracolumbar
      burst fractures. METHODS: The task force members identified search
      terms/parameters and a medical librarian implemented the literature search,
      consistent with the literature search protocol (see Appendix I), using the
      National Library of Medicine PubMed database and the Cochrane Library for the
      period from January 1, 1946 to March 31, 2015. RESULTS: A total of 906 articles
      were identified and 38 were selected for full-text review. Of these articles, 12
      articles met criteria for inclusion in this systematic review. CONCLUSION: There
      is grade A evidence for the omission of fusion in instrumented fixation for
      thoracolumbar burst fractures. There is grade B evidence that percutaneous
      instrumentation is as effective as open instrumentation for thoracolumbar burst
      fractures. QUESTION: Does the addition of arthrodesis to instrumented fixation
      improve outcomes in patients with thoracic and lumbar burst fractures?
      RECOMMENDATION: It is recommended that in the surgical treatment of patients with
      thoracolumbar burst fractures, surgeons should understand that the addition of
      arthrodesis to instrumented stabilization has not been shown to impact clinical
      or radiological outcomes, and adds to increased blood loss and operative time.
      Strength of Recommendation: Grade A. QUESTION: How does the use of minimally
      invasive techniques (including percutaneous instrumentation) affect outcomes in
      patients undergoing surgery for thoracic and lumbar fractures compared to
      conventional open techniques? RECOMMENDATION: Stabilization using both open and
      percutaneous pedicle screws may be considered in the treatment of thoracolumbar
      burst fractures as the evidence suggests equivalent clinical outcomes. Strength
      of Recommendation: Grade B The full version of the guideline can be reviewed at:
      https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic
      review-evidence-based-guidelines/chapter_12.

PMID- 30299487
TI  - Pre-treatment cerebrospinal fluid bacterial load correlates with inflammatory
      response and predicts neurological events during tuberculous meningitis
      treatment.
AB  - Background: Mycobacterium tuberculosis (Mtb) bacillary load in the brain of those
      with tuberculous meningitis (TBM) may reflect the host ability to control the
      pathogen and determine disease severity and treatment outcomes. Methods: We
      measured pre-treatment cerebrospinal fluid (CSF) Mtb bacterial load by GeneXpert
      in 692 adults with TBM. We sought to understand the relationship between CSF
      bacterial load and inflammation, and their respective impact on disease severity
      and treatment outcomes. Results: Ten-fold higher Mtb load was associated with
      increased disease severity (Odds Ratio=1.59, p=0.001 for grade 1 versus grade 3),
      and increased CSF neutrophils (r=0.364, p<0.0001) and cytokine concentrations
      (r=0.438, p<0.0001). High Mtb load predicted new neurological events after
      starting treatment (Multinomial logistic regression, p=0.005), but not death.
      Death was previously associated with attenuated inflammatory response at the
      start of treatment, with reduced cytokine concentrations compared to survivors.
      In contrast, patients with high pre-treatment CSF bacterial loads, cytokines, and
      neutrophils were more likely to subsequently suffer neurological events.
      Conclusions: Pre-treatment GeneXpert-derived Mtb load may be a useful predictor
      of neurological complications occurring during TBM treatment. Therapeutic
      strategies aimed at reducing neurological complications and deaths from TBM may
      need reassessment, given the evidence for their divergent pathogenesis.

PMID- 30299488
TI  - Genome-Wide Association Study of Susceptibility Loci for Radiation-Induced Brain
      Injury.
AB  - Background: Radiation-induced brain injury is a nonnegligible issue in the
      management of cancer patients treated by partial or whole brain irradiation. In
      particular, temporal lobe injury (TLI), a deleterious late complication in
      nasopharyngeal carcinoma, greatly affects the long-term life quality of these
      patients. Although genome-wide association studies (GWASs) have successfully
      identified single nucleotide polymorphisms (SNPs) associated with radiation
      toxicity, genetic variants contributing to the radiation-induced brain injury
      have not yet been assessed. Methods: We recruited and performed follow-up for a
      prospective observational cohort, Genetic Architecture of Radiotherapy Toxicity
      and Prognosis, using magnetic resonance imaging for TLI diagnosis. We conducted
      genome-wide association analysis in 1082 patients and validated the top
      associations in two independent cohorts of 1119 and 741 patients, respectively.
      All statistical tests were two-sided. Results: We identified a promoter variant
      rs17111237 (A > G, minor allele frequency [MAF] = 0.14) in CEP128 associated with
      TLI risk (hazard ratio = 1.45, 95% confidence interval = 1.26 to 1.66,
      Pcombined=3.18 * 10-7) which is in moderate linkage disequilibrium (LD) with
      rs162171 (MAF = 0.18, R2 = 0.69), the top signal in CEP128 (hazard ratio = 1.46,
      95% confidence interval = 1.29-1.66, Pcombined= 6.17 * 10-9). Combining the
      clinical variables with the top SNP, we divided the patients into different
      subgroups with varying risk with 5-year TLI-free rates ranging from 33.7% to
      95.5%. CEP128, a key component of mother centriole, tightly interacts with
      multiple radiation-resistant genes and plays an important role in maintaining the
      functional cilia, which otherwise will lead to a malfunction of the neural
      network. We found that A > G alteration at rs17111237 impaired the promoter
      activity of CEP128 and knockdown of CEP128 decreased the clonogenic cell survival
      of U87 cells under radiation. Noteworthy, 12.7% (27/212) of the GWAS-based
      associated genes (P < .001) were enriched in the neurogenesis pathway.
      Conclusions: This three-stage study is the first GWAS of radiation-induced brain
      injury that implicates the genetic susceptibility gene CEP128 involved in TLI
      development and provides the novel insight into the underlying mechanisms of
      radiation-induced brain injury.

PMID- 30299489
TI  - Evaluation of Intravenous Posaconazole Dosing and Pharmacokinetic Target
      Attainment in Pediatric Patients.
AB  - Limited data exist on intravenous (IV) posaconazole dosing and the risk for
      hepatotoxicity it confers to children. In this study, we evaluated dosing and
      resulting trough levels in 10 pediatric patients on IV posaconazole. A
      therapeutic level in these patients was achieved 95% of the time. We found a
      median minimum effective dose of 6.55 mg/kg of body weight. No correlation was
      found between the duration or posaconazole trough level and an increased alanine
      transaminase level.

PMID- 30299490
TI  - The AP2/ERF transcription factor SmERF115 positively regulates the biosynthesis
      of phenolic acids in Salvia miltiorrhiza.
AB  - Phenolic acids are an important kind of active secondary metabolites produced in
      Chinese medicinal plant Salviamiltiorrhiza, with the increasing market demand.
      Here, a novel AP2/ERF transcription factor SmERF115 was isolated and functionally
      characterized. SmERF115 was most responsive to methyl jasmonate (MJ) treatment
      and was localized in the nucleus. The phenolic acid production was obviously
      increased in SmERF115-overexpressing hairy roots but with decreased tanshinones
      content. Oppositely, silence of SmERF115 reduced phenolic acid level but with
      improved tanshinones content. The expression of key biosynthetic gene SmRAS1 was
      up-regulated in SmERF115 overexpression lines but was downregulated in SmERF115
      RNAi lines. Yeast one-hybrid (Y1H) and electrophoretic mobility shift assays
      (EMSAs) showed that SmERF115 directly binds to the promoter of SmRAS1, while Dual
      Luciferase (Dual-LUC) assays SmERF115 could activate expression of SmRAS1 in
      vivo. Furthermore, global transcriptomic analysis by RNA-seq revealed that
      expression of others genes such as PAL3, 4CL5, TAT3 and RAS4 were also increased
      in overexpressing line, implied that they were potentially involved in the
      SmERF115-mediated pathway. Therefore, SmERF115 is a positive regulator of
      salvianolic acid biosynthesis, which suggested that SmERF115 may be a potential
      target for further metabolic engineering of phenolic acid biosynthesis in
      S.miltiorrhiza.

PMID- 30299491
TI  - Immunogenicity and Reactogenicity of 13-Valent Pneumococcal Conjugate Vaccine
      Among Infants, Toddlers, and Children in Western Burkina Faso: Results From a
      Clinical Trial of Alternative Immunization Schedules.
AB  - Background: Many African countries have introduced pneumococcal conjugate vaccine
      (PCV) into their routine immunization program to reduce the burden of morbidity
      and death that results from Streptococcus pneumoniae infection, yet
      immunogenicity and reactogenicity data from the region are limited for the 2
      available PCV products. Methods: We conducted a randomized trial of 13-valent PCV
      (PCV13) in Bobo-Dioulasso, Burkina Faso. Infants received 3 doses of PCV at 6,
      10, and 14 weeks of age or at 6 weeks, 14 weeks, and 9 months of age; toddlers
      received 2 doses 2 months apart or 1 dose beginning at 12 to 15 months of age;
      and children received 1 dose between 2 and 4 years of age. We measured each
      participant's serotype-specific serum immunoglobulin G concentration and
      opsonophagocytic activity before and after vaccination. For each age group, we
      compared immune responses between study arms and between the standard schedule in
      our study and the PCV13-licensing trials. Results: In total, 280 infants, 302
      toddlers, and 81 children were assigned randomly and underwent vaccination; 268,
      235, and 77 of them completed follow-up, respectively. PCV13 resulted in low
      reactogenicity in all the study arms. The vaccine elicited a strong primary
      immune response in infants after 2 or more doses and in children aged 1 to 4
      years after 1 dose. Infants who received a booster dose exhibited a robust memory
      response. Immunogenicity was higher than or comparable to that observed in the
      PCV13-licensing trials for a majority of serotypes in all 3 age groups.
      Conclusions: PCV13 has a satisfactory immunogenicity and reactogenicity profile
      in this population. Our findings will help support decision making by countries
      regarding their infant and catch-up vaccination schedules.

PMID- 30299492
TI  - AL amyloidosis: advances in diagnostics and treatment.
AB  - AL amyloidosis (light chain; previously also called primary amyloidosis) is a
      systemic disease characterized by an amyloid deposition process affecting many
      organs, and which still has unsatisfactory survival of patients. The monoclonal
      light chains kappa (kappa) or lambda (lambda) or their fragments form the fibrils
      that deposit and accumulate in different tissues. Renal involvement is very
      frequent in AL amyloidosis and can lead to the development of nephrotic syndrome
      followed by renal failure in some cases. AL amyloidosis ultimately leads to
      destruction of tissues and progressive disease. With recent advances in the
      treatment, the importance of an early diagnosis of amyloidosis and correct
      assessment of its type is high. Histologic confirmation is based on Congo red
      detection of amyloid deposits in tissues but AL amyloidosis must also be
      distinguished from other systemic forms of amyloidoses with renal involvement,
      such as AA amyloidosis, amyloidosis with heavy chain deposition, fibrinogen
      Aalpha or ALECT2 (leukocyte chemotactic factor 2) deposition. Immunofluorescence
      (IF) plays a key role here. IF on formalin-fixed paraffin-embedded tissue after
      protease digestion, immunohistochemistry or laser microdissection with mass
      spectrometry should complete the diagnosis in unclear cases. Standard treatment
      with melphalan and prednisolone or with cyclophosphamide and dexamethasone has
      been replaced with newer drugs used for the treatment of multiple myeloma
      bortezomib, carfilzomib and ixazomib or thalidomide, lenalidomide and
      pomalidomide. High-dose melphalan supported by autologous stem cell
      transplantation remains the therapeutic option for patients with low-risk status.
      These new treatment options prolong survival from months to years and improve the
      prognosis in a majority of patients.

PMID- 30299494
TI  - Pandemic yellow fever: a potential threat to global health via travelers.

PMID- 30299493
TI  - Chronic Traumatic Encephalopathy Within an Amyotrophic Lateral Sclerosis Brain
      Bank Cohort.
AB  - Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative
      disorder linked to repetitive head impacts and has been associated with
      amyotrophic lateral sclerosis (ALS), a fatal, degenerative neuromuscular
      disorder. The Department of Veterans Affairs Biorepository Brain Bank (VABBB) is
      a tissue repository that collects antemortem disease progression data and
      postmortem central nervous system tissue from veterans with ALS. We set out to
      determine the frequency of co-morbid ALS and CTE in the VABBB cohort and to
      characterize the clinical, genetic, and pathological distinctions between
      participants with ALS only and those with both ALS and CTE (ALS+CTE). Of 155
      participants, 9 (5.8%) had neuropathologically confirmed ALS+CTE. Participants
      with ALS+CTE were more likely to have a history of traumatic brain injury (p <
      0.001), served during the first Persian Gulf War (p < 0.05), and to have more
      severe tau pathology within the frontal cortex and spinal cord (p < 0.05). The
      most common exposures to head impacts included contact sports (n = 5) and
      military service (n = 2). Clinically, participants with ALS+CTE were more likely
      to have bulbar onset ALS (p = 0.006), behavioral changes (p = 0.002), and/or mood
      changes (p < 0.001). Overall, compared with ALS in isolation, comorbid ALS+CTE is
      associated with a history of TBI and has a distinct clinical and pathological
      presentation.

PMID- 30299495
TI  - Dynamic network approach for the modelling of genomic sub-complexes in multi
      segmented viruses.
AB  - Viruses with segmented genomes, including pathogens such as influenza virus,
      Rotavirus and Bluetongue virus (BTV), face the collective challenge of packaging
      their genetic material in terms of the correct number and types of segments. Here
      we develop a novel network approach to predict RNA-RNA interactions between
      different genomic segments. Experimental data on RNA complex formation in the
      multi-segmented BTV genome are used to establish proof-of-concept of this
      technique. In particular, we show that trans interactions between segments occur
      at multiple specific sites, termed segment assortment signals (SASs) that are
      dispersed across each segment. In order to validate the putative trans acting
      networks, we used various biochemical and molecular techniques which confirmed
      predictions of the RNA network approach. A combination of mutagenesis and reverse
      genetics systems revealed that the RNA-RNA interacting sites identified are
      indeed responsible for segment assortment and complex formation, which are
      essential criteria for genome packaging. This paves the way for their
      exploitation as novel types of drug target, either to inhibit assembly, or for
      designing defective interfering particles containing an incomplete set of genomic
      segments.

PMID- 30299496
TI  - Evaluating the Addition of CO2 to Black Light Traps for Sampling Culicoides
      (Diptera: Ceratopogonidae) in Alberta.
AB  - We examined the effect of augmenting black light trap with CO2 at two release
      rates for monitoring and surveillance of Culicoides at northern latitudes.
      Species composition was highly correlated among black light (BL) traps with no
      CO2 (BL0 traps) and traps augmented with 300 and 1000 ml/min CO2 (BL300 and
      BL1000 traps, respectively); however, traps augmented with CO2 captured one to
      three more rare species than BL0 traps and can detect rare species that might be
      missed if BL0 traps were used. Addition of CO2 increased the number of
      individuals captured from 1.4 to 38.5-fold for BL300 traps and from 1.5 to 153.5
      fold for BL1000 traps. This advantage may be lost in areas with low abundance as
      might be expected at the limits of species. The daily probability of detecting a
      species was greater for traps augmented with CO2, but this can be compensated for
      by operating BL0 traps for sufficient time. The association between numbers
      captured by BL0 and BL300 and BL1000 traps also suggests that BL0 traps may
      provide useful measures of relative abundance for Culicoides sonorensis,
      Culicoides davisi, and Culicoides riethi, again providing the BL0 traps are left
      to operate for some period. Measurements of diel activity were influenced by trap
      type only for a single species and were primarily determined by solar radiation,
      temperature, and windspeed. Overall, the use of BL0 only traps for widescale
      surveys is supported, especially given their convenience.

PMID- 30299497
TI  - A 4-Year-Old Boy With an Unusual Bacterial Meningitis Infection.

PMID- 30299498
TI  - Association of thyroid status prior to transition to end-stage renal disease with
      early dialysis mortality.
AB  - Background: Advanced chronic kidney disease (CKD) patients, including those
      receiving dialysis, have a high prevalence of thyroid dysfunction. Although
      hypothyroidism is associated with higher death risk in end-stage renal disease
      (ESRD) patients, no studies have examined whether thyroid status in the pre-ESRD
      period impacts mortality after dialysis initiation. Methods: Among US veterans
      with CKD identified from the national Veterans Affairs database that transitioned
      to dialysis over the period from October 2007 to September 2011, we examined the
      association of pre-ESRD serum thyrotropin (TSH) levels averaged over the 1-year
      pre-dialysis ('prelude') period with all-cause mortality in the first year
      following dialysis initiation. Results: Among 15 335 patients in the 1-year
      prelude cohort, TSH levels >5.0 mIU/L were associated with higher mortality in
      expanded case-mix Cox models (reference: TSH 0.5-5.0 mIU/L): adjusted hazard
      ratio (aHR) [95% confidence interval (CI) 1.20 (1.07-1.33). Similar findings were
      observed for TSH >5.0 mIU/L and mortality in the 2- and 5-year cohorts: aHRs (95%
      CI) 1.11 (1.02-1.21) and 1.15 (1.07-1.24), respectively. Analyses of finer
      gradations of TSH in the 1-year prelude cohort demonstrated that incrementally
      higher levels >5.0 mIU/L were associated with increasingly higher mortality in
      expanded case-mix models (reference: TSH 0.5-3.0 mIU/L): aHRs (95% CI) 1.18 (1.04
      1.33) and 1.28 (1.03-1.59) for TSH levels >5.0-10.0 mIU/L and >10.0 mIU/L,
      respectively. In the 2- and 5-year cohorts, mortality associations persisted most
      strongly for those with TSH >10.0 mIU/L, particularly after laboratory covariate
      adjustment. Conclusions: Among new ESRD patients, there is a dose-dependent
      relationship between higher pre-ESRD TSH levels >5.0 mIU/L and post-ESRD
      mortality. Further studies are needed to determine the impact of TSH reduction
      with thyroid hormone supplementation in this population.

PMID- 30299499
TI  - Relationship between fluorescence yield and photochemical yield under water
      stress with intermediate light.
AB  - The associated dynamics between fluorescence (Fs) yield and photochemical (P)
      yield in changing environment are essential for understanding the relationship
      between photosynthesis and fluorescence. It was reported that the ratio of Fs
      yield and P yield tends to be constant under high light intensity (Liu et al.,
      2017). However, under intermediate and low light, the relationship between these
      two yields and its response to environment conditions need to be further
      explored. In this study, leaf-scale measurements of fluorescence parameters by
      pulse-amplitude modulation (PAM) technology were conducted for summer maize (Zea
      mays L.) grown under intermediate light condition (the light intensity above
      canopy was kept at 700 MUmol m-2 s-1) in a climate chamber. Plants were treated
      as moderate water stressed (45% - 55% of the field capacity) and non-water
      stressed (> 80% of the field capacity). Results showed that, decreasing of P
      yield was accompanied with increasing of Fs yield and non-photochemical quenching
      (NPQ) yield in response to moderate water stress under intermediate and low light
      condition. Fs yield was negatively correlated with P yield (p < 0.01) under
      intermediate and low light condition when soil water in root zone was sufficient.
      However, under water stress, their correlation was negative at low light level
      (PAR < 450 MUmol m-2 s-1), but it turned to be positive under higher light (PAR
      >= 450 MUmol m-2 s-1 and PAR <= 700 MUmol m-2 s-1); Fs yield was negatively
      related with P yield when NPQ yield was low, however they were synergistically
      and positively associated with each other when excessive light dissipating was
      dominated by NPQ. In conclusion, the relationship between fluorescence yield and
      photochemical yield is affected by light intensity and water status. The positive
      linear relationship may not be directly used to estimate photosynthesis by
      fluorescence emission for plants under intermediate and low light condition.

PMID- 30299500
TI  - Erratum to: Stereotactic Radiosurgery for Acromegaly: An International
      Multicenter Retrospective Cohort Study.

PMID- 30299501
TI  - Esrrb plays important roles in maintaining self-renewal of trophoblast stem cells
      (TSCs) and reprogramming somatic cells to induced TSCs.
AB  - Trophoblast stem cells (TSCs), which can be derived from the trophoectoderm of a
      blastocyst, have the ability to sustain self-renewal and differentiate into
      various placental trophoblast cell types. Meanwhile, essential insights into the
      molecular mechanisms controlling the placental development can be gained by using
      TSCs as the cell model. Esrrb is a transcription factor that has been shown to
      play pivotal roles in both embryonic stem cell (ESC) and TSC, but the precise
      mechanism whereby Esrrb regulates TSC-specific transcriptome during
      differentiation and reprogramming is still largely unknown. In the present study,
      we elucidate the function of Esrrb in self-renewal and differentiation of TSCs,
      as well as during the induced TSC (iTSC) reprogramming. We demonstrate that the
      precise level of Essrb is critical for stem state maintenance and further
      trophoblast differentiation of TSCs, as ectopically expressed Esrrb can partially
      block the rapid differentiation of TSCs in the absence of Fgf4. However, Esrrb
      depletion results in downregulation of certain key TSC-specific transcription
      factors, consequently causing a rapid differentiation of TSCs and these Esrrb
      deficient TSCs lose the ability of hemorrhagic lesion formation in vivo. This
      function of Esrrb is exerted by directly binding and activating a core set of TSC
      specific target genes including Cdx2, Eomes, Sox2, Fgfr4, and Bmp4. Furthermore,
      we show that Esrrb overexpression can facilitate the MEF-to-iTSC conversion.
      Moreover, Esrrb can substitute for Eomes to generate GEsTM-iTSCs. Thus, our
      findings provide a better understanding of the molecular mechanism of Esrrb in
      maintaining TSC self-renewal and during iTSC reprogramming.

PMID- 30299502
TI  - OpenProt: a more comprehensive guide to explore eukaryotic coding potential and
      proteomes.
AB  - Advances in proteomics and sequencing have highlighted many non-annotated open
      reading frames (ORFs) in eukaryotic genomes. Genome annotations, cornerstones of
      today's research, mostly rely on protein prior knowledge and on ab initio
      prediction algorithms. Such algorithms notably enforce an arbitrary criterion of
      one coding sequence (CDS) per transcript, leading to a substantial
      underestimation of the coding potential of eukaryotes. Here, we present OpenProt,
      the first database fully endorsing a polycistronic model of eukaryotic genomes to
      date. OpenProt contains all possible ORFs longer than 30 codons across 10
      species, and cumulates supporting evidence such as protein conservation,
      translation and expression. OpenProt annotates all known proteins (RefProts),
      novel predicted isoforms (Isoforms) and novel predicted proteins from alternative
      ORFs (AltProts). It incorporates cutting-edge algorithms to evaluate protein
      orthology and re-interrogate publicly available ribosome profiling and mass
      spectrometry datasets, supporting the annotation of thousands of predicted ORFs.
      The constantly growing database currently cumulates evidence from 87 ribosome
      profiling and 114 mass spectrometry studies from several species, tissues and
      cell lines. All data is freely available and downloadable from a web platform
      (www.openprot.org) supporting a genome browser and advanced queries for each
      species. Thus, OpenProt enables a more comprehensive landscape of eukaryotic
      genomes' coding potential.

PMID- 30299503
TI  - Xylem functioning, dysfunction and repair: a physical perspective and
      implications for phloem transport.
AB  - Xylem and phloem are the two main conveyance systems in plants allowing exchanges
      of water and carbohydrates between roots and leaves. While each system has been
      studied in isolation for well over a century, the coupling and coordination
      between them remains the subject of inquiry and active research and frames the
      scope of the review here. Using a set of balance equations, hazards of bubble
      formation and their role in shaping xylem pressure and its corollary impact on
      phloem pressure and sugar transport are featured. The behavior of an isolated and
      freely floating air bubble within the xylem is first analyzed so as to introduce
      key principles such as the Helmholtz free energy and its links to embryonic
      bubble sizes. These principles are extended by considering bubbles filled with
      water vapor and air arising from air seeding. Using this framework, key results
      about stability and hazards of bubbles in contact with xylem walls are discussed.
      A chemical equilibrium between phloem and xylem systems is then introduced to
      link xylem and osmotic pressures. The consequences of such a link for sugar
      concentration needed to sustain efficient phloem transport by osmosis in the
      loading zone is presented. Catastrophic cases where phloem dysfunction occurs are
      analyzed in terms of xylem function and its vulnerability to cavitation. A link
      between operating pressures in the soil system bounded by field capacity and
      wilting points and maintenance of phloem functioning are discussed as conjectures
      to be tested in the future.

PMID- 30299505
TI  - A standardization method to disentangle environmental information from axial
      trends of xylem anatomical traits.
AB  - Anatomical traits such as xylem conduit diameter and vessel connectivity are
      fundamental characteristics of the hydraulic architecture of vascular plants.
      Stem xylem conduits are narrow at the stem apex, and this confers resistance to
      embolisms that might otherwise be induced by large, negative water potentials at
      the top of tall trees. Below the apex, conduits progressively widen and this
      characteristic minimizes effects of path length on total hydraulic resistance.
      While interconnections among xylem vessels have been noted for decades, their
      role(s) are not fully clarified. For example, we do not know if they allow water
      to bypass embolized vessels, or increase the risk of spread of embolisms, or how
      their arrangement varies within a tree. Here we demonstrate the benefit of
      removing the independent effect of stem length on assessment of effects of
      external (e.g., climatic) factors on such xylem traits. We measured the hydraulic
      diameter (Dh) and vessel conductivity index (VCI) along the stem of 21
      shrubs/trees of similar height (1.19 < H < 5.45 m) belonging to seven Acacia
      species, across a wide aridity gradient in Australia. All trees showed similar
      scaling exponents of Dh (b = 0.33) and VCI (b = 0.53) vs axial distance from the
      apex (L), thus conforming with general patterns in woody plants. After de
      trending for L, neither Dh (P = 0.21) nor VCI (P = 0.109) differed across the
      aridity gradient. We found that across a wide gradient of aridity, climate had no
      effect on xylem anatomy of Acacia spp, which was instead dictated by axial
      distances from stem apices. We argue that the use of standardization procedures
      to filter out intrinsic patterns of vascular traits is an essential step in
      assessing climate-driven modifications of xylem architecture.

PMID- 30299506
TI  - STAT3 gain of function: a new aetiology of severe rheumatic disease.

PMID- 30299507
TI  - Bilaterally Reduced Intraepidermal Nerve Fiber Density in Unilateral CRPS-I.
AB  - Objective: Findings regarding small nerve fiber damage in complex regional pain
      syndrome type I (CRPS-I) are not uniform, and studies have not included a matched
      healthy control group. The aim was to assess intraepidermal nerve fiber density
      (IENFD) in relation to thermal sensitivity of the same skin areas in CRPS-I
      patients and a gender- and age-matched healthy control group. Methods: IENFD was
      investigated in skin biopsies from the CRPS-affected and contralateral limbs of
      eight CRPS-I patients and from an equivalent site in eight gender- and age
      matched healthy controls (HCs). Thermal thresholds (cold/warm detection, cold-
      and heat-pain detection) were assessed on the affected limb, the matching
      contralateral limb, and on the equivalent limbs of HCs, and participants rated
      the intensity of cold/heat and pain to static thermal stimuli (5  degrees C and
      40  degrees C). Results: IENFD was significantly lower in both the affected and
      contralateral limbs of CRPS-I patients than HCs, but IENFD did not differ between
      the affected and contralateral limbs of patients. The heat pain threshold was
      lower in the affected CRPS-I limb than in HCs, but all other thermal thresholds
      were similar in both groups. CRPS-I patients rated the cold stimulus as colder
      and more painful in the affected limb, and the warm stimulus as hotter,
      bilaterally, than the HCs. Conclusions: CRPS-I may be associated with bilateral
      small fiber damage, and perhaps small fiber neuropathy and bilateral disturbances
      in thermo-sensory perception. These disturbances could stem from a systemic
      response to injury or might increase the risk of developing CRPS-I after physical
      trauma.

PMID- 30299504
TI  - Genetics of Human Longevity From Incomplete Data: New Findings From the Long Life
      Family Study.
AB  - The special design of the Long Life Family Study provides a unique opportunity to
      investigate the genetics of human longevity by analyzing data on exceptional
      lifespans in families. In this article, we performed two series of genome wide
      association studies of human longevity which differed with respect to whether
      missing lifespan data were predicted or not predicted. We showed that the use of
      predicted lifespan is most beneficial when the follow-up period is relatively
      short. In addition to detection of strong associations of SNPs in APOE, TOMM40,
      NECTIN2, and APOC1 genes with longevity, we also detected a strong new
      association with longevity of rs1927465, located between the CYP26A1 and MYOF
      genes on chromosome 10. The association was confirmed using data from the Health
      and Retirement Study. We discuss the biological relevance of the detected SNPs to
      human longevity.

PMID- 30299509
TI  - Influence of dietary zinc concentration and supplemental zinc source on nutrient
      digestibility, zinc absorption, and retention in sheep.
AB  - The objective of this study was to assess whether supplemental Zn source or
      concentration would affect ruminant Zn retention and nutrient digestibility.
      Thirty-six weaned crossbred Polypay wethers, were sorted by BW to 3 periods and
      stagger started on a common diet (22 mg Zn/kg DM) for a 52-d depletion period.
      Day 52 BW was used to assign Zn treatments (3 lambs/treatment/period): no
      supplemental Zn (CON), or supplemental Zn (40 mg Zn/d) from Zn sulfate (ING; Zinc
      Nacional, Monterrey, SA, Mexico), Zn methionine (ORG; Zinpro 120; Zinpro, Eden
      Prairie, MN), or Zn hydroxychloride (HYD; IntelliBond Z; Micronutrients USA LLC,
      Indianapolis, IN). On day 53 (day 1 of Zn treatments), lambs were moved to
      metabolism crates for 10 d of adaptation and 5 d of total fecal and urine
      collection. Blood for plasma Zn analysis was collected on day 52 and day 68. Data
      were analyzed as a randomized complete design with fixed effects of treatment,
      period and the interaction, which was significant (P >= 0.19) for day 68 plasma
      Zn but was removed for all other variables. Contrast statements were used to
      separate treatment means: CON vs. ZINC (ING, ORG, HYD), ING vs. HYD, and ORG vs.
      HYD. Day 52 plasma Zn concentrations were similar when CON was compared with ZINC
      (P = 0.84), and when ING and ORG were compared with HYD (P >= 0.19). Dry matter
      and neutral detergent fiber digestibility were lesser in ORG compared with HYD (P
      = 0.05) and organic matter and acid detergent fiber digestibility tended (P <=
      0.08) to be lesser in ORG compared with HYD. Intake and fecal excretion of Zn was
      lesser, while apparent absorption of Zn was greater, in CON compared with ZINC (P
      <= 0.001). Zinc retained as a percent of Zn intake was greater in CON compared
      with ZINC (P = 0.001). Zinc retained (mg/d) was similar in CON compared with ZINC
      (P = 0.58) and when ING or ORG were compared with HYD (P >= 0.83). There was a
      treatment * period interaction for day 68 plasma Zn where treatments did not
      differ for periods 1 and 3 but ORG lambs had increased plasma Zn in period 2
      compared with other treatments (P = 0.02). Lambs receiving no supplemental Zn had
      increased apparent absorption, suggesting Zn absorption may be upregulated in
      these lambs. Similarities in Zn retention across treatments suggests Zn
      requirements of these lambs were met regardless of supplementation concentration
      or source. Nutrient digestibility was improved in HYD lambs compared with ORG,
      and further work is needed to clarify the influence of supplemental Zn source on
      nutrient digestion.

PMID- 30299510
TI  - Heparin-binding protein release is strongly induced by Leptospira spp. and is a
      candidate for an early diagnostic marker of human leptospirosis.
AB  - Background: Leptospirosis is one of the most widespread zoonosis worldwide,
      caused by spirochetes of the genus Leptospira. Efficient leptospirosis early
      diagnostic methods are still lacking and acute disease presents with non-specific
      symptomatology, being often misdiagnosed. The leptospires pathogenic processes
      and virulence mechanisms remain virtually unknown. In severe infections,
      hemostatic impairment is frequently observed, and pathophysiological
      complications often develop when the host response is modulated by the pathogen.
      The neutrophil heparin-binding protein (HBP) is an inflammatory mediator and
      potent inducer of vascular leakage. Results: In this study, we found that
      leptospires and their secreted products induce the release of HBP from stimulated
      neutrophils through a controlled degranulation mechanism. We acknowledged two
      leptospiral proteins as able to induce HBP degranulation. These findings have
      clinical implications, as high levels of HBP were detected in serum of
      leptospirosis patients, especially at the early phase of the disease. Conclusion:
      In conclusion, we describe a new mechanism by which the leptospirosis
      pathophysiological complications may arise, such as vascular leakage and oedema
      formation. We also propose HBP as a new early screening biomarker for human
      leptospirosis.

PMID- 30299508
TI  - Targeting Exercise Interventions to Patients With Cancer in Need: An Individual
      Patient Data Meta-Analysis.
AB  - Background: Exercise effects in cancer patients often appear modest, possibly
      because interventions rarely target patients most in need. This study
      investigated the moderator effects of baseline values on the exercise outcomes of
      fatigue, aerobic fitness, muscle strength, quality of life (QoL), and self
      reported physical function (PF) in cancer patients during and post-treatment.
      Methods: Individual patient data from 34 randomized exercise trials (n = 4519)
      were pooled. Linear mixed-effect models were used to study moderator effects of
      baseline values on exercise intervention outcomes and to determine whether these
      moderator effects differed by intervention timing (during vs post-treatment). All
      statistical tests were two-sided. Results: Moderator effects of baseline fatigue
      and PF were consistent across intervention timing, with greater effects in
      patients with worse fatigue (Pinteraction = .05) and worse PF (Pinteraction =
      .003). Moderator effects of baseline aerobic fitness, muscle strength, and QoL
      differed by intervention timing. During treatment, effects on aerobic fitness
      were greater for patients with better baseline aerobic fitness (Pinteraction =
      .002). Post-treatment, effects on upper (Pinteraction < .001) and lower
      (Pinteraction = .01) body muscle strength and QoL (Pinteraction < .001) were
      greater in patients with worse baseline values. Conclusion: Although exercise
      should be encouraged for most cancer patients during and post-treatments,
      targeting specific subgroups may be especially beneficial and cost effective. For
      fatigue and PF, interventions during and post-treatment should target patients
      with high fatigue and low PF. During treatment, patients experience benefit for
      muscle strength and QoL regardless of baseline values; however, only patients
      with low baseline values benefit post-treatment. For aerobic fitness, patients
      with low baseline values do not appear to benefit from exercise during treatment.

PMID- 30299511
TI  - Seroprevalence, risk factors and spatial distribution of West Nile virus in
      Jordan.
AB  - Background: This is the first countrywide study of the seroprevalence, risk
      factors and spatial distribution of West Nile virus (WNV) in Jordan. Methods: A
      cross-sectional sample of 801 participants was administered a comprehensive
      questionnaire survey and tested for WNV immunoglobulin G antibodies. Results: The
      point seroprevalence rate for WNV infection was 8.61% (95% confidence interval
      6.8 to 10.8). Multivariate regression analysis demonstrated that sex, age,
      climate, income and drinking water source were significantly associated with
      seropositivity (p<=0.05). Males had 1.73 greater odds of infection compared with
      females. Compared with 15 to 29-year-olds, adults 30-49 y old and adults >=50 y
      old had 2.0 and 3.1 greater odds of infection, respectively. Individuals living
      in the Jordan Valley and Badia had 22.2 and 7.2 times greater odds of infection,
      respectively, compared with individuals living in the highlands. Households with
      an income of <US$750/month had 1.8 greater odds of infection compared with those
      with higher household incomes. Individuals using spring lakes as a drinking water
      source had 5.1 greater odds of infection than people who used water from any
      other source. Conclusions: This study demonstrates that WNV is circulating in
      Jordan and should be considered as a differential diagnosis in medical cases
      presenting with nervous system symptoms, especially for older populations living
      in the Jordan Valley and Badia areas.

PMID- 30299514
TI  - Reply to Kempker and Blumberg.

PMID- 30299513
TI  - Gullible Travails.

PMID- 30299515
TI  - Returns to Operating Room After Neurosurgical Procedures in a Tertiary Care
      Academic Medical Center: Implications for Health Care Policy and Quality
      Improvement.
AB  - BACKGROUND: Return to the operating room (ROR) has been put forth by the National
      Quality Forum and the American College of Surgeons as a surgical quality
      indicator. However, current quality metrics fail to consider the nature and
      etiology of the ROR. OBJECTIVE: To provide a comprehensive description of all
      reoperations after neurosurgical procedures and assess the validity of ROR as a
      quality measure in neurosurgery. METHODS: We retrospectively analyzed all
      neurosurgical procedures performed in a high-volume, tertiary care academic
      medical center between June 1, 2014 and December 31, 2016. Based on a system
      constructed and validated at our institution, we classified RORs into (a)
      unplanned related, (b) planned return due to complications, (c) planned-staged
      return, or (d) unrelated return. RESULTS: A total of 9200 unique neurosurgical
      cases were identified, of which 788 had an ROR within 45 d (8.6%). Median time to
      ROR (interquartile range) was 9 d (4-15). Specifically, 4.2% were planned-staged
      returns, 3.4% were unplanned related, 0.3% were unrelated, and 0.6% were planned
      because of previous complications. Cranial procedures had the highest unplanned
      ROR rate (4.2%), followed by spinal (2.8%) and peripheral nerve (0.4%). The most
      common reason for an unplanned ROR was wound complication/surgical site infection
      (34.3%), followed by hematoma evacuation (13.9%) and cerebrospinal fluid (CSF)
      leak (11.3%). CONCLUSION: Unplanned RORs were relatively rare and most commonly
      associated with wound complication, postoperative hematoma, and CSF leak. To
      better reflect surgical quality, ROR metrics should indicate whether the return
      was planned or unrelated.

PMID- 30299516
TI  - Association of DAT1 Genetic Variants with Habitual Sleep Duration in the UK
      Biobank.
AB  - Short sleep duration has been linked to negative health effects, but is a complex
      phenotype with many contributing factors, including genetic. We evaluated 27
      common SNPs in candidate genes previously reported to be associated with other
      sleep variables for association with self-reported habitual sleep duration in the
      UK Biobank in 111,975 individuals of European ancestry. Genetic variation in DAT1
      (rs464049) was significantly associated with sleep duration after correction for
      multiple testing (p=4.00x10-5), whereas SNPs correlated to a previously studied
      VNTR in DAT1 were not significant in this population. We also replicated a
      previously reported association in DRD2. Independent replication of these
      associations and a second signal in DRD2 (rs11214607) was observed in an
      additional 261,870 participants of European ancestry from the UK Biobank. Meta
      analysis confirmed genome-wide significant association of DAT1 rs464049 (G, beta
      (se) = -0.96 (0.18) mins/allele, p = 5.71x10-10) and study-wide significant
      association of DRD2 (rs17601612, C, beta (SE) = -0.66 (0.18) mins/allele, p =
      1.77x10-5; rs11214607, C, beta (SE) = 1.08 (0.24) mins/allele, p = 1.39x10-6).
      Overall, SNPs in two dopamine-related genes were significantly associated with
      sleep duration, highlighting the important link of the dopamine system with adult
      sleep duration in humans.

PMID- 30299517
TI  - Tree host-pathogen interactions as influenced by drought timing: linking
      physiological performance, biochemical defence and disease severity.
AB  - There is increasing concern about tree mortality around the world due to climatic
      extremes and associated shifts in pest and pathogen dynamics. Yet, empirical
      studies addressing the interactive effect of biotic and abiotic stress on plants
      are very rare. Therefore, in this study, we examined the interaction between
      drought stress and a canker pathogen, Quambalaria coyrecup, on the eucalypt -
      Corymbia calophylla (marri), which is experiencing increasing drought stress. We
      hypothesized that drought stress would increase marri's susceptibility to canker
      disease, and cankers would have the largest negative effect on plants that are
      already drought stressed before pathogen inoculation. To test the hypotheses, in
      a glasshouse, marri saplings were exposed to drought either before or after
      pathogen inoculation, or were well-watered or droughted throughout the experiment
      either with or without inoculation. Canker development was greater in well
      watered saplings than in droughted saplings, with the fastest development
      occurring in well-watered saplings that had experienced drought stress before
      inoculation. Irrespective of water treatments, marri saplings employed phenol
      based localized biochemical defence against the pathogen. Drought reduced
      photosynthesis and growth, however, a negative effect of canker disease on
      saplings' physiological performance was only observed in well-watered saplings.
      In well-watered saplings, canker-induced loss of sapwood function contributed to
      reduced whole-plant hydraulic conductance, photosynthesis and growth. The results
      provide evidence that timing of drought stress influences host physiology, and
      host condition influences canker disease susceptibility through differences in
      induced biochemical defence mechanisms. The observations highlight the importance
      of explicitly incorporating abiotic and biotic stress, as well as their
      interactions, in future studies of tree mortality in drought-prone regions
      worldwide.

PMID- 30299520
TI  - Gait Stability in Older Adults during Level-ground Walking: The Attentional Focus
      Approach.
AB  - Objectives: The objective is to investigate the effect of attentional focus
      instructions on gait stability during level-ground walking among older adults.
      Method: We recruited 140 community-dwelling older adults (mean age = 70.3 years,
      SD = 4.7 years) from elderly community centres in Hong Kong. The experiment
      included assessments on participant's characteristics and walking trials. During
      walking trials, each participant was invited to walk at a self-selected pace
      along a 6-metre walkway. Either internal focus instructions (Internal condition),
      external focus instructions (External condition) or no instruction (Control
      condition) were given in a randomized order for 3 trials per condition, giving a
      total of 9 walking trials. Spatial and temporal gait parameters were measured.
      Results: Results showed significantly higher body sway and variability of swing
      and stance time under Internal condition relative to External and Control
      conditions. Moreover, reduced velocity and shorter steps were demonstrated under
      Internal condition relative to External and Control conditions. Discussion:
      External focus instructions did not improve gait stability in older adults when
      compared to Control condition. Internal focus instructions appear to compromise
      gait stability. Future research should investigate if walking instructions that
      refer to body movements explicitly compromise gait rehabilitation for older
      adults in clinical settings.

PMID- 30299518
TI  - Sex Differences in Hypertension: Where We Have Been and Where We Are Going.
AB  - While it has been known since the 1940s that men have greater increases in blood
      pressure (BP) compared with women, there have been intense efforts more recently
      to increase awareness that women are also at risk for developing hypertension and
      that cardiovascular diseases (CVDs) are the leading causes of death among both
      men and women in the United States. With the release of the 2017 Hypertension
      Clinical Guidelines, 46% of adults in the United States are now classified as
      hypertensive, and hypertension is the primary modifiable risk factor for the
      development of CVD. This increase in the prevalence of hypertension is reflected
      in an increase in prevalence among both men and women across all demographics,
      although there were greater increases in the prevalence of hypertension among men
      compared with women. As a result, the well-established gender difference in the
      prevalence of hypertension is even more pronounced and now extends into the sixth
      decade of life. The goals of this review are to (i) review the historical
      clinical trial data and hypertension guidelines from the perspective of both
      genders and then (ii) review the role of the renin-angiotensin system and T-cell
      activation in contributing to sex differences in BP control.

PMID- 30299519
TI  - Bivalent Human Papillomavirus Vaccine Effectiveness in a Japanese Population:
      High Vaccine-Type-Specific Effectiveness and Evidence of Cross-Protection.
AB  - Background: Proactive recommendations for human papillomavirus (HPV) vaccines in
      Japan have been suspended for 5 years because of safety concerns. While no
      scientific evidence exists to substantiate these concerns, one reason given for
      not reinstating recommendations is the lack of reliable vaccine effectiveness
      (VE) data in a Japanese population. This study reports the VE of the bivalent HPV
      vaccine in Japanese women aged 20-22 years. Methods: During cervical screening
      between 2014 and 2016, women had Papanicolaou smears and HPV tests performed and
      provided data about their sexual history. Estimates of VE for vaccine-targeted
      HPV type 16 (HPV16) and 18 and cross-protection against other types were
      calculated. Results: Overall, 2197 women were tested, and 1814 were included in
      the analysis. Of these, 1355 (74.6%) were vaccinated, and 1295 (95.5%) completed
      the 3-dose schedule. In women sexually naive at vaccination, the pooled VEs
      against HPV16 and 18 and for HPV31, 45, and 52 were 95.5% (P < .01) and 71.9% (P
      < .01), respectively. When adjusted for number of sex partners and birth year,
      pooled VEs were 93.9% (P = .01) and 67.7% (P = .01) for HPV16 and 18 and HPV31,
      45, and 52, respectively. Conclusions: The bivalent HPV vaccine is highly
      effective against HPV16 and 18. Furthermore, significant cross-protection against
      HPV31, 45, and 52 was demonstrated and sustained up to 6 years after vaccination.
      These findings should reassure politicians about the VE of bivalent HPV vaccine
      in a Japanese population.

PMID- 30299521
TI  - Fatigue in adults with cerebral palsy: A three-year follow-up study.
AB  - OBJECTIVES: To describe the course of fatigue over a 3-year follow-up period in
      adults with cerebral palsy and to investigate the association of known
      determinants of fatigue (i.e. demographic characteristics and/or body
      composition) with change in fatigue. METHODS: Forty-one adults with cerebral
      palsy from a previous study of fatigue were invited to participate in a follow-up
      study. Twenty-three adults with cerebral palsy (Gross Motor Function
      Classification System (GMFCS) levels I-V; mean age 38 years 2 months, standard
      deviation (SD) 14 years 1 month)) agreed to participate (convenience sample).
      Fatigue was measured with the Fatigue Impact and Severity Self-Assessment (FISSA,
      range 31-157) questionnaire. The course of fatigue is described at group,
      subgroup (GMFCS) and individual levels. RESULTS: The mean FISSA score for all
      participants was 84.0 (SD 27.7) at baseline and 91.7 (SD 26.7) at follow-up.
      Despite variations among individuals in the change of fatigue, there was no
      statistically significant difference in FISSA score over time (p = 0.087, 95%
      confidence interval (95% CI) -16.7 to 1.22). No known determinants of fatigue
      predictive of change in FISSA scores were found. DISCUSSION: Fatigue appears to
      be relatively stable within adults with cerebral palsy over time, with a variable
      presentation between individuals and across GMFCS levels. Care providers should
      monitor and discuss fatigue in young individuals with cerebral palsy in order to
      attenuate fatigue later in life.

PMID- 30299522
TI  - Differences in cardiovascular health in ambulatory persons with cerebral palsy.
AB  - OBJECTIVE: To compare cardiovascular health variables and physical activity
      levels of adolescents and adults with cerebral palsy who are Gross Motor Func
      tion Classification System (GMFCS) levels I and II. METHODS: Eleven adolescents
      (mean age 13.1 (standard deviation (SD) 2.1) years) and 14 adults (mean age 31.7
      (SD 10.4) years)) with cerebral palsy were included, grouped by their GMFCS level
      (level I (n = 12); level II (n = 13)). Assessments of cardiovascular health, body
      composition and physical activity levels were performed. Cardiovascular variables
      included resting blood pressure and carotid artery intima media thickness. Body
      composition included height, weight, body mass index, and waist circumference.
      Physical activity was measured using accelerometry. RESULTS: Adjusting for age
      between GMFCS levels (GMFCS I mean 17.3 (SD 5.2); GMFCS II mean 29.3 (SD 14.1)
      years, p = 0.011), significant differences were evident for moderate-to-vigorous
      physical activity per day (GMFCS I median 45.8 (interquartile range (IQR) 32.4
      75.1); GMFCS II median 16.4 (IQR 13.0, 25.0) min/day, p = 0.011), height (GMFCS I
      mean 1.63 (SD 0.14); GMFCS II mean 1.56 (SD 0.12) m, p = 0.010), mean arterial
      pressure (GMFCS I mean 84.6 (SD 7.8); GMFCS II mean 89.4 (SD 8.5) mmHg, p =
      0.030), and carotid artery intima media thickness (GMFCS I mean 0.431 (SD 0.06);
      GMFCS II mean 0.489 (SD 0.04), p = 0.026). CONCLUSION: Individuals with cerebral
      palsy who were GMFCS level I had lower mean arterial pressure, thinner carotid
      artery intima media thickness, and engaged in a greater amount of moderate-to
      vigorous physical activity per day than those who were GMFCS level II. Clinicians
      should acknowledge that ambulatory individuals with cerebral palsy could have
      differing cardiovascular health profiles and should monitor these cardiovascular
      variables and discuss physical activity during healthcare visits, regardless of
      age.

PMID- 30299523
TI  - Efficacy of hyaluronic acid after knee arthroscopy: A systematic review and meta
      analysis.
AB  - OBJECTIVE: To investigate the effect of hyaluronic acid on functional recovery
      and pain control in patients following knee arthroscopy. DESIGN: A systematic
      review and meta-analysis was conducted to explore the efficacy of hyaluronic acid
      following knee arthroscopy. SUBJECTS AND METHODS: Randomized controlled trials
      (RCTs) assessing the effect of hyaluronic acid in knee arthroscopy were included.
      A meta-analysis was performed using the random-effect model. RESULTS: Six RCTs
      involving 310 patients were included in the meta-analysis. Overall, compared with
      control intervention following knee arthroscopy, hyaluronic acid treatment was
      found to significantly increase Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) scores (mean difference 11.43; 95% confidence
      intervals (95% CI) 1.39-21.47; p = 0.03), but had no impact on pain scores at 2
      weeks (mean difference -0.16; 95% CI -0.81-0.49; p = 0.63), pain scores at 6
      weeks (mean difference 0.01; 95% CI -0.86-0.89; p = 0.98), pain scores at 12
      weeks (mean difference -0.51; 95% CI -1.56-0.53; p = 0.34). In addition, pain on
      motion was significantly reduced after knee arthroscopy (risk ratio (RR) 0.22;
      95% CI 0.06-0.79; p = 0.02). CONCLUSION: Compared with control intervention after
      knee arthroscopy, hyaluronic acid treatment was found to significantly improve
      WOMAC score and decrease pain on motion, but had no substantial influence on pain
      scores at 2, 6 and 12 weeks after knee arthroscopy.

PMID- 30299524
TI  - Validity and feasibility of a temperature sensor for measuring use and non-use of
      orthopaedic footwear.
AB  - OBJECTIVE: Adherence is a prerequisite for the effectiveness of orthopaedic
      footwear. The aim of this study is to assess the validity of a new temperature
      sensor for objective assessment of footwear use and non-use. DESIGN:
      Observational study. METHODS: The validity of a temperature sensor (Orthotimer,
      Balingen, Germany) to discriminate between time periods of use and non-use of
      footwear over a period of 48 h was assessed using 3 algorithms, in 10 healthy
      participants (mean age 32.8 years (standard deviation (SD) 14.1 years)). Footwear
      use measured with the sensor was compared with a reference standard, footwear use
      measured with a time-lapse sports camera secured to the shoe. MAIN OUTCOME
      MEASURE: Hours of footwear use. RESULTS: Mean footwear use measured with the
      camera was 8.10 (SD 2.46) h per day. Mean footwear uses measured with the sensor
      and calculated with the 3 algorithms were 8.16 (SD 2.37), 8.86 (SD 2.48) and 4.91
      (SD 3.17) h per day for the Groningen algorithm, algorithm-25, and algorithm-29,
      respectively. The correlation between footwear use assessed with the camera and
      with the sensor was: rGroningen = 0.995, ralg25 = 0.919 and ralg29 = 0.680).
      CONCLUSION: The temperature sensor is a valid instrument to measure footwear use
      and non-use when using the Groningen algorithm.

PMID- 30299525
TI  - Assessing the effectiveness of rehabilitation and optimizing effectiveness in
      routine clinical work.

PMID- 30299526
TI  - Paediatric cerebral palsy prevalence and high-risk factors in Henan Province,
      Central China.
AB  - OBJECTIVE: To evaluate the prevalence of, and risk factors for, cerebral palsy in
      Henan province, China. METHODS: The prevalence of cerebral palsy in children aged
      0-6 years between September 2011 and September 2012 was investigated using a
      stratified-clustered-random sampling method. An age-, sex- , and residence
      matched control group of typically developing children was recruited. Univariate
      analysis and multinomial logistic regression analysis were used to identify risk
      factors associated with cerebral palsy. RESULTS: The prevalence of cerebral palsy
      in Henan province was 2.37 per 1,000 live births. Risk factors included: moving
      into a newly painted room; complicating maternal diseases (infection, heart
      disease, hypertension, anaemia, diabetes, kidney disease) during pregnancy; high
      gravidity (> 3); foetal asphyxia; low birth-weight (< 2,500 g); and hypoxic
      ischaemic encephalopathy. CONCLUSION: The prevalence of cerebral palsy in Henan
      province was 2.37 per 1,000 live births. Parents and clinicians should be aware
      of the risk factors for cerebral palsy.

PMID- 30299527
TI  - [Introduction of prehospital blood transfusion programme in Sweden: experiences
      from a physician staffed helicopter emergency medical service].
AB  - In 2016, physician staffed helicopter emergency medical service (VGR HEMS) became
      the first Swedish prehospital service to routinely carry and transfuse red blood
      cells. In this report we describe our implementation and present our results,
      with preliminary analysis of our data. Out of 1 336 patients a total of 34
      patients (2,5 %) were transfused without any adverse events. Our demography is
      predominantly male and the most common mechanism of injury is trauma. Amongst the
      most common interventions were endotracheal intubation, thoracostomy and CPR.
      Preliminary analysis showed an increase in median systolic blood pressure and
      decrease in median heart rate after prehospital blood transfusion. Half of the
      patients that received CPR had return of spontaneous circulation (ROSC). We
      conclude that prehospital blood transfusion in a Swedish physician-staffed
      helicopter emergency medical service is feasible and safe.

PMID- 30299529
TI  - ?

PMID- 30299528
TI  - [Postural orthostatic tachycardia syndrome].
AB  - Postural orthostatic tachycardia syndrome (POTS) is a condition where the patient
      experiences tachycardia (a rise in heart rate of at least 30 beats per minute, 40
      in people between the ages of 12 and 19) upon assuming the upright position, in
      the absence of orthostatic hypotension (a fall in systolic blood pressure of more
      than 20 mmHg). The majority of patients are young women. Symptoms are experienced
      frequently during standing, and include dizziness, fatigue, palpitations,
      tremulousness, blurred vision and sometimes syncope - although presyncope is more
      common. The diagnosis requires that symptoms have been present for at least six
      months and lack another medical explanation. The pathophysiology is believed to
      be multifactorial; peripheral sympathetic denervation, excessive sympathetic
      drive, hypovolemia and deconditioning have been reported in POTS. Patient
      education is fundamental in the management of POTS, including information
      regarding symptoms and exacerbating factors as well as methods for increasing
      arterial pressure. Exercise is believed to be effective. Several drugs can be
      used to relieve symptoms, although none of them are licensed for the treatment of
      POTS. We describe a case that illustrates that POTS can be debilitating, which
      requires awareness of the condition among clinicians.

PMID- 30299530
TI  - [The large hiatal hernia should be acknowledged and respected].
AB  - A hiatal hernia is a partial or total dislocation of the stomach, sometimes
      together with other intraabdominal organs, through the diaphragmatic esophageal
      hiatus into the thoracic cavity. The condition is common and often asymptomatic.
      Old age and obesity are risk factors for developing hiatal hernia. Small hernias
      might induce gastroesophageal reflux, which usually is satisfactorily treated
      pharmacologically. Larger hiatal hernias are more often associated with
      obstructive symptoms including dysphagia, vomiting or discomfort/pain due to
      compression of adjacent organs/tissues. In severe cases, large hiatal hernias may
      become incarcerated with ischemia in herniated tissues and need of acute surgical
      intervention. The risk of complications in association with operation for large
      hiatal hernias is high, particularly in acute surgery and in elderly patients
      with co-morbidities.

PMID- 30299531
TI  - [How many patients had their colon investigated within five years prior to
      colorectal cancer diagnosis?]
AB  - We aimed to investigate the prevalence of patients who had their colon
      investigated five years to three months before their colorectal cancer (CRC) was
      diagnosed. All patients diagnosed between January 1st 2016 and September 14th
      2017 in the county of Vasterbotten, Sweden were included (n=307). The proportion
      of patients with CRC who had their colon investigated before diagnosis was 7%
      (n=22). The median time from the index examination to the date of diagnosis of
      CRC was 1013 days (IQR 639 days). In addition, 16% of the patients had a positive
      FIT test (F-Hb) and 23% had anemia that was known more than three months prior to
      diagnosis. A long duration of anemia before diagnosis was significantly more
      common in men than in women (31% vs 16%; p=0.003). We conclude that the incidence
      of "missed" CRC are low but may be improved by a thorough adherence to
      colonoscopy guidelines. We found that a positive iFOBT and anemia often were
      detected more than three months prior to diagnosis.

PMID- 30299532
TI  - ?

PMID- 30299533
TI  - Prevalence of second canal in the mesiobuccal root of permanent maxillary molars
      from a Turkish subpopulation: a cone-beam computed tomography study.
AB  - BACKGROUND: Permanent maxillary molar teeth have the most complex root and canal
      systems. This study aimed to determine the frequency and the localization of
      secondary mesiobuccal canal (MB2) in the mesiobuccal roots of permanent maxillary
      molars in a Turkish subpopulation using cone beam computed tomography (CBCT) and
      compare them by different age groups and gender. MATERIALS AND METHODS: In this
      retrospective study, a total of 800 maxillary molar teeth in 200 subjects were
      investigated. The distances between canals were calculated from the center point
      of the MB2 canal (PMB2) to the center point of the mesiobuccal canal (PMB1) and
      the center point of the palatal canal (PP). RESULTS: The incidence of MB2 canals
      was found to be 33.5% (23.2% in females, 43.6% in males) in 200 subjects. A
      significant difference was found between age groups and genders in terms of the
      frequency of MB2 (p<0.05). The distances between PMB1-PMB2 were 2.95 +/- 0.58 mm,
      3.08 +/- 0.67 mm for 1MM and 2MM, respectively. For 1MM and 2MM, the averages of
      PMB2-PP distances were 5.81 +/- 1.09 mm and 5.55 +/- 1.09 mm, respectively. The
      contralateral formation of the MB2 canals was 90.5% (16, 26) in the first molars
      and 93.9% in the second molars (17, 27). The contingency rate in the first
      quadrant was 86.0% (16, 17) and 83.5% (26, 27) in the second quadrant.
      CONCLUSIONS: It is important for the clinician to know the high probability of
      finding the MB2 canal in the maxillary first and second molars. CBCT imaging can
      facilitate the clinician to detect complex and variable root canal anatomy.

PMID- 30299534
TI  - Accessory head of the flexor pollicis longus muscle: anatomical study and
      clinical significance.
AB  - BACKGROUND: The accessory head of the flexor pollicis longus (AHFPL) has an
      oblique trajectory from medial to lateral aspect of the forearm below the flexor
      digitorum superficialis muscle and then joins the flexor pollicis longus muscle.
      When the anterior interosseous nerve (AIN) courses underneath the muscle belly of
      the AHFPL an entrapment neuropathy may occur, known as anterior interosseous
      nerve syndrome (AINS). MATERIALS AND METHODS: This descriptive cross-sectional
      study evaluated 106 fresh upper extremities. When the AHFPL was present, its
      fascicle was traced up to evaluate the origin site. The morphometric variables
      were measured using a digital micrometer (Mitutoyo, Japan). The relationship
      between the AHFLP and the AIN was evaluated. RESULTS: The AHFPL was found in 34
      (32.1%) of the 106 forearms. The AHFPL arose from the flexor digitorum
      superficialis muscle in 16 forearms (47.1%), the medial epicondyle of the humerus
      in ten forearms (29.4%) and the coronoid process of ulna in eight forearms
      (23.5%). The average total length of the AHFPL was 94.11 +/- 10.33 mm. The AIN
      was located lateral to the AHFPL in three forearms (8.8%), posterolateral in
      seven forearms (20.6%) and posterior in 24 forearms (70.6%). CONCLUSIONS: This
      study performed in a South American population sample revealed a prevalence of
      the AHFPL in a lower range compared to previous studies in North Americans and
      Asians. The AIN coursed more frequently underneath the muscle belly of AHFPL.
      This finding has clinical significance in the onset of the AINS and the
      subsequent surgical procedure for the AIN decompression.

PMID- 30299535
TI  - The play skills of children with high-functioning autism spectrum disorder in
      peer-to-peer interactions with their classmates: A multiple case study design.
AB  - BACKGROUND/AIM: Children with ASD are known to have lower play skills than their
      typically developing peers. However, the play skills of children with ASD are
      rarely investigated using observational measures in the context of their everyday
      peer-to-peer play interactions. To explore the play skills of children with ASD
      and their aged matched classmates during a peer-to-peer play interaction.
      METHODS: Using convenience sampling, four children with ASD (5-11 years)
      attending mainstream schools were recruited for this multiple case design study.
      Each child with ASD was paired with one of their aged matched typically
      developing classmates. Children's play skills were measured using the Test of
      Playfulness (ToP). Additional case data were collected through teacher-reported
      social skills and behaviours. Rasch analysis was utilised to convert raw ToP
      scores into an interval level overall score for each child. Children's individual
      ToP item scores, social skills and behaviours are presented by case. RESULTS: The
      two children with ASD who had the highest ToP scores, also had the highest
      teacher-reported social skills. All children with ASD had greatest difficulty on
      ToP items reflecting suspension of reality and framing. Two children with ASD had
      higher ToP scores than their classmate. In these two cases, the classmates had
      similar play skills of children with ASD. CONCLUSION: The play skills of children
      with ASD varied by case. Across the cases, teacher-reported social skills,
      classmate age and existence of friendship between children were all factors
      observed to influence play. These findings require replication and investigation
      in larger scale studies.

PMID- 30299536
TI  - Symbiotic dinitrogen fixation is seasonal and strongly regulated in water-limited
      environments.
AB  - Plants, especially perennials, growing in drylands and seasonally dry ecosystems
      are uniquely adapted to dry conditions. Legume shrubs and trees, capable of
      symbiotic dinitrogen (N2 ) fixation, often dominate in drylands. However, the
      strategies that allow symbiotic fixation in these ecosystems, and their influence
      on the nitrogen cycle, are largely unresolved. We evaluated the climatic,
      biogeochemical and ontogenetic factors influencing nitrogen fixation in an
      abundant Mediterranean legume shrub, Calicotome villosa. We measured nodulation,
      fixation rate, nitrogen allocation and soil biogeochemistry in three field sites
      over a full year. A controlled experiment evaluated differences in plant
      regulation of fixation as a function of soil nutrient availability and seedling
      and adult developmental stages. We found a strong seasonal pattern, shifting
      between high fixation rates during the rainy season at flowering and seed-set
      times to almost none in the rainless season. Under controlled conditions, plants
      downregulated fixation in response to soil nitrogen availability, but this
      response was stronger in seedlings than in adult shrubs. Finally, we did not find
      elevated soil nitrogen under N2 -fixing shrubs. We conclude that seasonal
      nitrogen fixation, regulation of fixation, and nitrogen conservation are key
      adaptations influencing the dominance of dryland legumes in the community, with
      broader consequences on the ecosystem nitrogen cycle.

PMID- 30299537
TI  - The first case of severe acute hemolytic transfusion reaction caused by anti-Sc2.
AB  - BACKGROUND: Alloantibodies to the low-frequency antigen Scianna-2 (Sc2) have been
      implicated in cases of hemolytic disease of the fetus and newborn but never in
      hemolytic transfusion reactions (HTRs); thus, the clinical significance of anti
      Sc2 has yet to be fully addressed. STUDY DESIGN AND METHODS: A 26-year-old woman
      with thalassemia presented rigors, fever, nausea, abdominal pain, and hemolytic
      biochemistry after exposure to 75 mL of plasma-reduced red blood cells (RBCs).
      The RBC unit was issued by electronic crossmatch but was 3+ incompatible on
      recrossmatch by gel indirect antiglobulin test (IAT). The patient had anti-Sc2
      previously identified, but considered to be clinically insignificant. The
      transfusion history was reviewed and a monocyte monolayer assay (MMA) was
      performed. RESULTS: The patient was investigated for a RBC reaction 9 years
      prior, when she developed symptoms of HTR. The RBC unit was crossmatched by
      immediate spin due to consistent screen negativity. Full crossmatch found the RBC
      1+ incompatible by gel IAT with both pre/post samples, while direct antiglobulin
      test was negative (pre) and 1+ immunoglobulin G positive (post). The antibody
      remained unidentified and she was committed to gel IAT crossmatch. Two-years
      later, the specificity to Sc2 was deduced when one RBC unit was found 3+
      incompatible. Finally, the transfusion reaction reported herein occurred when she
      received by happenstance RBCs from the same donor who was associated with the
      remote reaction 9 years earlier. MMA yielded highly positive phagocytic indices
      only for Sc2+ RBCs, including the donor's RBCs that triggered the severe HTR.
      CONCLUSION: This is the first case of HTR caused by anti-Sc2 confirmed by
      clinical findings and MMA.

PMID- 30299538
TI  - The opioid epidemic in the United States-Overview, origins, and potential
      solutions.

PMID- 30299539
TI  - Reply to Patients with revised surgical resection margins are best studied as a
      distinct group.

PMID- 30299540
TI  - The added value of geriatric screening and assessment for predicting overall
      survival in older patients with cancer.
AB  - BACKGROUND: The aim of this study was to determine and compare the added
      prognostic value of screening tools, geriatric assessment (GA) components, and GA
      summaries to clinical information for overall survival (OS) in older patients
      with cancer. METHODS: A screening and a 10-item GA were systematically performed
      in patients >=70 years old with cancer. Cox regression analyses were conducted to
      evaluate the added prognostic value for OS of screening tools, GA, and GA
      summaries to clinical information (age, stage, and tumor type) in 2 cohorts (A
      and B). Cox models were compared on the basis of the Akaike information criterion
      and the concordance probability estimate. The 2 cohorts for the analyses were
      similar but independent. RESULTS: A complete case analysis was available for 763
      patients (median age, 76 years) in cohort A and for 402 patients (median age, 77
      years) in cohort B. In both cohorts, most individual GA components were
      independent prognostic factors for OS. Nutritional status (assessed with the Mini
      Nutritional Assessment Short Form) and functional status (assessed with the
      Instrumental Activities of Daily Living) consistently displayed a strong capacity
      to predict OS. Less consistent results were found for screening tools. GA
      summaries performed the best in comparison with the screening tools and the
      individual GA components. CONCLUSIONS: Most individual GA components, especially
      nutritional status and functional status, are prognostic factors for OS in older
      patients with cancer. GA summaries provide more prognostic information than
      individual GA components but only moderately improve the prognostic baseline
      model with clinical information.

PMID- 30299541
TI  - Leaf litter decay rates differ between mycorrhizal groups in temperate, but not
      tropical, forests.
AB  - Whereas the primary controls on litter decomposition are well established, we
      lack a framework for predicting interspecific differences in litter decay within
      and across ecosystems. Given previous research linking tree mycorrhizal
      association with carbon and nutrient dynamics, we hypothesized that the two
      dominant mycorrhizal groups in forests - arbuscular mycorrhizal (AM) and
      ectomycorrhizal (ECM) fungi - differ in litter decomposition rates. We compiled
      leaf litter chemistry and decay data for AM- and ECM-associating angiosperms and
      gymnosperms (> 200 species) from temperate and tropical/subtropical, and
      investigated relationships among decay rates, mycorrhizal association, phylogeny
      and climate. In temperate forests, AM litters decayed faster than ECM litters,
      with litter nitrogen and phylogeny best explaining variation in litter decay. In
      sub/tropical forests, we found no significant difference in litter decay rate
      between mycorrhizal groups, and variation in decay rates was best explained by
      litter phosphorus. Our results suggest that knowledge of tree mycorrhizal
      association may improve predictions of species effects on ecosystem processes,
      particularly in temperate forests where AM and ECM species commonly co-occur,
      providing a predictive framework for linking litter quality, organic matter
      dynamics and nutrient acquisition in forests.

PMID- 30299542
TI  - A phase 1, open-label, dose escalation study of intravenous paricalcitol in
      combination with gemcitabine in patients with advanced malignancies.
AB  - BACKGROUND: Calcitriol, the active analogue of vitamin D, is antiproliferative
      and enhances the cytotoxicity of several anticancer agents, including
      gemcitabine. The vitamin D receptor (VDR) is expressed in the tumor stroma and
      treatment with VDR ligands results in stromal remodeling and increased
      intratumoral gemcitabine delivery. Furthermore, calcitriol can decrease the
      activity of the gemcitabine deactivating enzyme cytidine deaminase (CDD). Because
      hypercalcemia has been the most worrisome calcitriol-related adverse event, the
      less hypercalcemic agent paricalcitol may be preferred for further investigation.
      METHODS: The authors undertook a phase 1 study of gemcitabine in combination with
      escalating doses of paricalcitol administered weekly intravenously in patients
      with advanced cancers. A standard 3+3 dose escalation schema was used.
      Pharmacokinetic assessment of gemcitabine and its metabolite 2',2'
      difluorodeoxyuridine (dFdU) was performed. Pharmacodynamic assessment of
      paricalcitol was performed by measurement of CDD activity in peripheral blood
      mononuclear cells. RESULTS: A total of 44 patients were enrolled. Somnolence was
      the main dose-limiting toxicity. The highest dose of paricalcitol administered
      was 10.5 ug/kg. Hypercalcemia was infrequent and mild in severity. Paricalcitol
      did not appear to affect the pharmacokinetics of gemcitabine and dFdU. Evaluation
      of CDD activity was available for 9 patients; no clear trend for CDD activity
      after treatment with paricalcitol was established. The overall response rate was
      4%; the rate of disease control was 67% in patients who were pretreated with
      gemcitabine. Progression-free and overall survival were 3.4 months and 6.5
      months, respectively. CONCLUSIONS: Paricalcitol can be administered safely in
      doses up to 7 ug/kg weekly with fixed dose rate gemcitabine without dose-limiting
      hypercalcemia. To the best of the authors' knowledge, the maximum tolerated dose
      has not been formally established to date. Preliminary clinical activity deserves
      further exploration.

PMID- 30299543
TI  - Repeated domestication of melon (Cucumis melo) in Africa and Asia and a new close
      relative from India.
AB  - PREMISE OF THE STUDY: The domestication history of melon is still unclear. An
      African or Asian origin has been suggested, but its closest wild relative was
      recently revealed to be an Australian species. The complicated taxonomic history
      of melon has resulted in additional confusion, with a high number of
      misidentified germplasm collections currently used by breeders and in genomics
      research. METHODS: Using seven DNA regions sequenced for 90% of the genus and the
      major cultivar groups, we sort out described names and infer evolutionary origins
      and domestication centers. KEY RESULTS: We found that modern melon cultivars go
      back to two lineages, which diverged ca. 2 million years ago. One is restricted
      to Asia (Cucumis melo subsp. melo), and the second, here described as C. melo
      subsp. meloides, is restricted to Africa. The Asian lineage has given rise to the
      widely commercialized cultivar groups and their market types, while the African
      lineage gave rise to cultivars still grown in the Sudanian region. We show that
      C. trigonus, an overlooked perennial and drought-tolerant species from India is
      among the closest living relatives of C. melo. CONCLUSIONS: Melon was
      domesticated at least twice: in Africa and Asia. The African lineage and the
      Indian C. trigonus are exciting new resources for breeding of melons tolerant to
      climate change.

PMID- 30299544
TI  - Retrograde signalling as an informant of circadian timing.
AB  - The circadian system comprises interlocking transcriptional-translational
      feedback loops that regulate gene expression and consequently modulate plant
      development and physiology. In order to maximize utility, the circadian system is
      entrained by changes in temperature and light, allowing endogenous rhythms to be
      synchronized with both daily and seasonal environmental change. Although a great
      deal of environmental information is decoded by a suite of photoreceptors, it is
      also becoming apparent that changes in cellular metabolism also contribute to
      circadian timing, through either the stimulation of metabolic pathways or the
      accumulation of metabolic intermediates as a consequence of environmental stress.
      As the source of many of these metabolic byproducts, mitochondria and
      chloroplasts have begun to be viewed as environmental sensors, and rapid
      advancement of this field is revealing the complex web of signalling pathways
      initiated by organelle perturbation. This review highlights recent advances in
      our understanding of how this metabolic regulation influences circadian timing.

PMID- 30299545
TI  - Do tall tree species have higher relative stiffness than shorter species?
AB  - PREMISE OF THE STUDY: In 1757 Leonhard Euler demonstrated that to avoid bending
      tall columns needed to be stiffer but not stronger than shorter columns of equal
      diameter and material density. Many researchers have concluded that trees have a
      fixed stiffness to basic density ratio, and therefore, trees adjust for
      increasing height by adding mass to adjust stem form. But the wood science
      literature points to considerable variance in stiffness with respect to green
      wood density. METHODS: Using the vast global repository of green wood mechanical
      properties, we compared relative stiffness and relative strength between taller
      and shorter species. For North American trees, we examined stem moisture
      distribution. KEY RESULTS: For all regions of the world, taller species on
      average possessed greater stiffness, but not strength, than shorter species of
      equal basic specific gravity. We looked for a possible universal mechanism that
      might allow taller tree species to adjust stiffness without affecting xylem
      specific gravity and concluded that the evidence points to a decrease in
      cellulose microfibril angle in structural cell walls combined with possible
      increases in holocellulose percentage. The evidence is strongest for conifers. We
      also showed that tall conifers have the ability to adjust the distribution of
      xylem moisture to maximize conduction while minimizing column load. CONCLUSIONS:
      Our research reveals that taller trees have developed internal stem adjustments
      to minimize diameter increase while attaining ever-greater heights, thus enabling
      these taller species to reduce energy expended on biomass accumulation while
      gaining greater access to solar radiation.

PMID- 30299546
TI  - Patients with revised surgical resection margins are best studied as a distinct
      group.

PMID- 30299547
TI  - JPEN Journal Club 39. Validating a Surrogate.

PMID- 30299548
TI  - Poor Social Support and Unemployment Are Associated With Negative Affect in Home
      Parenteral Nutrition-Dependent Patients With Chronic Intestinal Failure.
AB  - BACKGROUND: Home parenteral nutrition (HPN) provides life-sustaining treatment
      for people with chronic intestinal failure (CIF). Poor quality of life is
      reported in association with the burden of HPN and the underlying condition
      leading to intestinal failure (IF). However, levels of negative affect (NA),
      incorporating anxiety and depression, have not been reported in CIF. This study
      examined the occurrence and risk factors for NA in a large CIF population using
      the validated Hospital Anxiety & Depression Scale (HADS) and Multidimensional
      Scale of Perceived Social Support (MSPSS) questionnaires. METHODS: A survey pack
      including HADS and MSPSS were distributed to patients managed by a specialist IF
      center. Data from these measures were analyzed against factors including
      underlying disease, length of time receiving HPN, employment status, and
      demographics. RESULTS: Of 85 patients who completed this study, 56% had clinical
      levels of anxiety and/or depression. Linear regression analysis confirmed
      significant correlations between social support and HADS scores, with poorer
      perceived social support associated with higher levels of NA (-0.26 MSPSS +
      33.24; R2 = 0.29; P < .0001). There were also significant associations between
      unemployment and higher anxiety (P = .004), depression (P = .008), and NA scores
      (P = .003). By contrast, there were no significant associations between patient
      age, duration of time receiving parenteral nutrition, pathophysiological
      mechanisms of CIF, and NA levels. CONCLUSIONS: Clinical anxiety and depression
      are common, affecting more than half of patients with CIF. Patients with poor
      social networks and those of working age who have ceased employment are
      particularly vulnerable and should be prioritized for psychological support
      because of their elevated risk.

PMID- 30299549
TI  - Analytic second derivatives for the efficient electrostatic embedding in the
      fragment molecular orbital method.
AB  - The analytic second derivatives of the energy with respect to nuclear coordinates
      are developed for restricted Hartree-Fock and density functional theory, based on
      the two-body fragment molecular orbital method (FMO) and combined with the
      electrostatic embedding potential, self-consistently determined by point charges
      for far separated fragments and electron densities for near fragments. The
      accuracy of the method is established with respect to FMO using the exact
      embedding potential based on electron densities and to full calculations without
      fragmentation. The computational efficiency of parallelization is measured on the
      K supercomputer and the method is applied to simulate infrared spectra of two
      proteins, Trp-cage (PDB: 1L2Y) and crambin (1CRN). The nature of the vibrations
      in the Amide I peak of crambin and the Tyr symmetric stretch peak in Trp-cage are
      analyzed in terms of localized vibrations. (c) 2018 Wiley Periodicals, Inc.

PMID- 30299550
TI  - Representation of DNA environment: Spiral staircase distribution function.
AB  - In the present study, we investigated the local structure of DNA and its
      environment using a new visualization technique. The spiral staircase
      distribution function (SSDF) is determined as two-dimensional density
      distribution of atoms of water and ligands in local reference frames linked with
      each base pair of poly-DNA molecule, either GC or AT. This property of SSDF
      provides opportunity to study sequence-specific binding of ions, peptides, and
      other agents derived from a molecular dynamics computer simulation. The spatial
      structure of double-stranded DNA environment in water solution containing either
      Mg2+ or Na+ ions was investigated using of SSDF. The distributions of ions around
      GC and AT base pairs are shown separately. It is observed that Mg2+ ions interact
      with DNA atoms by means of the layer of water molecules and penetrate into the
      major groove only. Na+ ions have a direct contact with DNA atoms and penetrate
      both into the major and minor grooves of DNA. (c) 2018 Wiley Periodicals, Inc.

PMID- 30299551
TI  - Metal-catalyzed alkyne oxidation/C?H functionalization: Effects of oxidant,
      temperature, and metal catalyst on chemoselectivity.
AB  - Gold-catalyzed intermolecular alkyne oxidation has attracted much synthetic
      attention, but mostly suffering undesired over-oxidation. Recent experiments
      demonstrated that over-oxidation could be dramatically suppressed in zinc(II)
      catalyzed intermolecular alkyne oxidation/C?H functionalization. By means of
      first-principle density functional theory calculations, we explored the mechanism
      of the M-catalyzed intermolecular alkyne oxidations (M = Zn(OTf)2 and Au+ PR3 )
      as well as the effects of oxidants, temperature, and metal catalysts on
      chemoselectivity, in an effort to disclose the origin of the extraordinary
      chemoselectivity pertaining to zinc catalysis. Our calculations indicate that the
      Zn-catalyzed intermolecular alkyne oxidation/C?H functionalization proceeds by a
      Friedel-Crafts alkylation mechanism rather than metal carbene insertion
      mechanism. The chemoselectivity of C?H functionalization against over-oxidation
      in Zn catalysis, in comparison with gold catalysis, can be jointly controlled by
      four factors: (1) the use of less nucleophilic N-oxide, (2) the enhanced
      electrophilicity and carbocationic nature of the carbenic site in the alpha-oxo
      metal carbenoid intermediate, (3) enhanced steric repulsion to incoming oxidant
      exerted by bulky ancillary ligand in the close nearby of the carbenic site to
      disfavor intermolecular over-oxidation and (4) the large negative value of
      activation entropy in the intermolecular over-oxidation pathway, that jointly
      give rise to lower activation free energy for the intramolecular cyclization/C?H
      functionalization pathway than for the intermolecular over-oxidation pathway. (c)
      2018 Wiley Periodicals, Inc.

PMID- 30299553
TI  - Defence-related priming and responses to recurring drought: Two manifestations of
      plant transcriptional memory mediated by the ABA and JA signalling pathways.
AB  - Collective evidence from agricultural practices and from scientific research has
      demonstrated that plants can alter their phenotypic responses to repeated biotic
      and abiotic stresses or their elicitors. A coordinated reaction at the
      organismal, cellular, and genome levels has suggested that plants can "remember"
      an earlier stress and modify their future responses, accordingly. Stress memory
      may increase a plant's survival chances by improving its tolerance/avoidance
      abilities and may provide a mechanism for acclimation and adaptation.
      Understanding the mechanisms that regulate plant stress memory is not only an
      intellectually challenging topic but has important implications for agricultural
      practices as well. Here, I focus exclusively on specific aspects of the
      transcription memory in response to recurring dehydration stresses and the memory
      type responses to insect damage in a process known as "priming." The questions
      discussed are (a) whether/how the two memory phenomena are connected at the level
      of transcriptional regulation; (b) how differential transcription is achieved
      mechanistically under a repeated stress; and (c) whether similar molecular and/or
      epigenetic mechanisms are involved. Possible biological relevance of
      transcriptional stress memory and its preservation in plant evolution are also
      discussed.

PMID- 30299552
TI  - A kinetics study of ligand substitution reaction on dinuclear platinum complexes:
      Stochastic versus deterministic approach.
AB  - The kinetics on a basic ligand substitution reaction on dinuclear platinum
      complexes [Pt(PEt3 )2 PhPt(PEt3 )2 ]2+ and [Pt(PEt3 )2 PhCOPhPt(PEt3 )2 ]2+ ,
      with the ligands pyridine and 3-chloropyridine, is studied. This is a fundamental
      step in a self-assembly, and the time evolution has been observed with a new
      experimental technique, QASAP (quantitative analysis of self-assembly process),
      which is recently developed by Hiraoka's group. As a result of numerical
      calculations based on master equation, we succeed in specifying the reaction rate
      constants with a simple reaction model. In addition, the time evolutions of all
      the intermediate components produced and consumed in chemical reaction are
      revealed, including those unobserved in the experiments. The convergence behavior
      of the existence ratios of specific chemical species calculated with the
      stochastic algorithm method is compared with those obtained from deterministic
      formalism based on rate equations, revealing a clear dependence on the number of
      constituent molecules. (c) 2018 Wiley Periodicals, Inc.

PMID- 30299554
TI  - Nitric oxide inhibits biofilm formation by Vibrio fischeri via the nitric oxide
      sensor HnoX.
AB  - Nitric oxide (NO) is an important defense molecule secreted by the squid Euprymna
      scolopes and sensed by the bacterial symbiont, Vibrio fischeri, via the NO sensor
      HnoX. HnoX inhibits colonization through an unknown mechanism. The genomic
      location of hnoX adjacent to hahK, a recently identified positive regulator of
      biofilm formation, suggested that HnoX may inhibit colonization by controlling
      biofilm formation, a key early step in colonization. Indeed, the deletion of hnoX
      resulted in early biofilm formation in vitro, an effect that was dependent on
      HahK and its putative phosphotransfer residues. An allele of hnoX that encodes a
      protein with increased activity severely delayed wrinkled colony formation.
      Control occurred at the level of transcription of the syp genes, which produce
      the polysaccharide matrix component. The addition of NO abrogated biofilm
      formation and diminished syp transcription, effects that required HnoX. Finally,
      an hnoX mutant formed larger symbiotic biofilms. This work has thus uncovered a
      host-relevant signal controlling biofilm and a mechanism for the inhibition of
      biofilm formation by V. fischeri. The study of V. fischeri HnoX permits us to
      understand not only host-associated biofilm mechanisms, but also the function of
      HnoX domain proteins as regulators of important bacterial processes.

PMID- 30299555
TI  - High inpatient dose of opioid at discharge compared to home dose predicts
      readmission risk in sickle cell disease.

PMID- 30299556
TI  - Metabolic analysis of the melatonin biosynthesis pathway using chemical labeling
      coupled with liquid chromatography-mass spectrometry.
AB  - Characterization of the melatonin (MLT) biosynthesis pathway in plants is still
      limited. Additionally, a metabolomic analysis of MLT biosynthesis in plants is
      still a challenge due to analyte structural and chemical diversity, low analyte
      abundances, and plant matrix complexities. Herein, a sensitive liquid
      chromatography-mass spectrometry (LC-MS) method enabling the simultaneous
      determination of seven plant MLT biosynthetic metabolites was developed. In the
      proposed strategy, the targeted metabolites, which included tryptophan (Trp),
      tryptamine (TAM), 5-hydroxytryptophan (5HTP), serotonin (5HT), N-acetylserotonin
      (NAS), 5-methoxytryptamine (5MT), and MLT, were purified from plant extracts
      using a one-step dispersive solid-phase extraction (DSPE). The samples were then
      chemically labeled with dansyl chloride (DNS-Cl), followed by analysis using LC
      MS. The limit of detection (LOD) values ranged from 0.03 to 1.36 pg/mL and
      presented a 22- to 469-fold decrease when compared to the unlabeled metabolites.
      Due to the high sensitivity of the proposed method, the consumption of plant
      materials was reduced to 10 mg FW. Ultimately, the established method was
      utilized to examine the distributions of MLT and its intermediates in rice shoots
      and roots with or without cadmium (Cd) stress. The results suggested that under
      normal condition, MLT may also be generated via a Trp/TAM/5HT/5MT/MLT path
      (Pathway II) in addition to the previously reported Trp/TAM/5HT/NAS/MLT path
      (Pathway I), although Pathway I was shown to be dominant. During Cd stress, MLT
      was also shown to be produced through these two pathways, with Pathway II shown
      to be dominant in rice shoots and roots.

PMID- 30299557
TI  - More teeth in more elderly: Periodontal treatment needs in Germany 1997-2030.
AB  - OBJECTIVE: With more teeth retained for longer in an ageing population,
      population-wide periodontal treatment needs may increase. We assessed and
      projected periodontal treatment needs from 1997 to 2030 in Germany. METHODS:
      Partial-mouth probing-pocket depths (PPDs) from repeated waves (1997, 2005, 2014)
      of the nationally representative German Oral Health Studies were transformed into
      full-mouth PPDs via decision-tree-based ensemble-modelling. In line with German
      healthcare-regulations, teeth with PPD >= 4 mm were regarded as needing
      periodontal treatment. Weighted means were interpolated cross-sectionally by
      fitting spline-curves and then regressed longitudinally 1997-2030. RESULTS: In
      1997, younger adults (35-44 years old) had a mean of 7.4 teeth needing treatment
      (overall 93.8 million teeth); this decreased to 4.8 teeth (47.3 million teeth) in
      2014. For 2030, we project 3.2 teeth (33.7 million teeth). In seniors, an
      increase was recorded (1997: 4.5 teeth, 33.5 million teeth; 2014: 7.5 teeth, 63.4
      million teeth); this is expected to continue until 2030 (to 12.2 teeth, 140.8
      million teeth). The cumulative number of teeth needing treatment increased from
      2000 (355 million) to 2015 (365 million), and will increase further to 2030 (464
      million). CONCLUSIONS: Population-wide periodontal treatment needs may increase
      until 2030, mainly in the elderly. Concepts for addressing, these growing needs
      are required.

PMID- 30299558
TI  - Mechanism and rate constants of the CH2 + CH2 CO reactions in triplet and singlet
      states: A theoretical study.
AB  - Ab initio and density functional CCSD(T)-F12/cc-pVQZ-f12//B2PLYPD3/6-311G**
      calculations have been performed to unravel the reaction mechanism of triplet and
      singlet methylene CH2 with ketene CH2 CO. The computed potential energy diagrams
      and molecular properties have been then utilized in Rice-Ramsperger-Kassel-Marcus
      Master Equation (RRKM-ME) calculations of the reaction rate constants and product
      branching ratios combined with the use of nonadiabatic transition state theory
      for spin-forbidden triplet-singlet isomerization. The results indicate that the
      most important channels of the reaction of ketene with triplet methylene lead to
      the formation of the HCCO + CH3 and C2 H4 + CO products, where the former channel
      is preferable at higher temperatures from 1000 K and above. In the C2 H4 + CO
      product pair, the ethylene molecule can be formed either adiabatically in the
      triplet electronic state or via triplet-singlet intersystem crossing in the
      singlet electronic state occurring in the vicinity of the CH2 COCH2 intermediate
      or along the pathway of CO elimination from the initial CH2 CH2 CO complex. The
      predominant products of the reaction of ketene with singlet methylene have been
      shown to be C2 H4 + CO. The formation of these products mostly proceeds via a
      well-skipping mechanism but at high pressures may to some extent involve
      collisional stabilization of the CH3 CHCO and cyclic CH2 COCH2 intermediates
      followed by their thermal unimolecular decomposition. The calculated rate
      constants at different pressures from 0.01 to 100 atm have been fitted by the
      modified Arrhenius expressions in the temperature range of 300-3000 K, which are
      proposed for kinetic modeling of ketene reactions in combustion. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30299559
TI  - Exploring the applicability of density functional tight binding to transition
      metal ions. Parameterization for nickel with the spin-polarized DFTB3 model.
AB  - In this work, we explore the applicability and limitations of the current third
      order density functional tight binding (DFTB3) formalism for treating transition
      metal ions using nickel as an example. To be consistent with recent
      parameterization of DFTB3 for copper, the parametrization for nickel is conducted
      in a spin-polarized formulation and with orbital-resolved Hubbard parameters and
      their charge derivatives. The performance of the current parameter set is
      evaluated based on structural and energetic properties of a set of nickel
      containing compounds that involve biologically relevant ligands. Qualitatively
      similar to findings in previous studies of copper complexes, the DFTB3 results
      are more reliable for nickel complexes with neutral ligands than for charged
      ligands; nevertheless, encouraging agreement is noted in comparison to the
      reference method, B3LYP/aug-cc-pVTZ, especially for structural properties,
      including cases that exhibit Jahn-Teller distortions; the structures also compare
      favorably to available X-ray data in the Cambridge Crystallographic Database for
      a number of nickel-containing compounds. As to limitations, we find it is
      necessary to use different d shell Hubbard charge derivatives for Ni(I) and
      Ni(II), due to the distinct electronic configurations for the nickel ion in the
      respective complexes, and substantial errors are observed for ligand binding
      energies, especially for charged ligands, d orbital splitting energies and
      splitting between singlet and triplet spin states for Ni(II) compounds. These
      observations highlight that future improvement in intra-d correlation and ligand
      polarization is required to enable the application of the DFTB3 model to complex
      transition metal ions. (c) 2018 Wiley Periodicals, Inc.

PMID- 30299560
TI  - New aspects of quantum electrodynamics on electronic structure and dynamics.
AB  - Application of Alpha-oscillator theory to quantum electrodynamics (QED) solves
      the mystery (Feynman) of the double-slit phenomenon involved in the foundation of
      quantum mechanics (QM). Even if with the same initial condition given, different
      spots on the screen can be predicted deterministically with no introduction of
      hidden variables. The interference pattern is similar to, but cannot be
      reproduced quantitatively by, that of the QM wave function, contrary to many
      years-anticipation: a new prediction, awaiting experimental test over and above
      the Bohr-Einstein gedanken experiment. The general proof has already been
      published in Ref. [3a] and the concrete numerical algorithm of the extended
      normal mode technique for concrete trajectory of one electron in Ref. [3b]. In
      this article, (1) the new "interpretation" of the QED wave function is given in
      section "Interpretation of Wave Function in QED": the QED wave function used in
      the extended normal mode technique gives probability density distribution
      function of the initial values of trajectories. Moreover, (2) for the sake of
      demonstration of this new interpretation, the time-independent stationary state
      QM wave function is substituted to the QED wave function in section "Internal
      Self-Stress of Energetic Particles": the QED wave function is realized by
      internal self-stress revealed as energy density at the initial conditions. The
      renewed energy density is applied to study a unified scheme for generalized
      chemical reactivity. This is a new kind of chemical force acting in between
      electrons not in between nuclei. This paves a way for more advanced time
      dependent simulation of electronic structure and dynamics in chemical reaction
      dynamics by tracing trajectories of many electrons. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 30299561
TI  - The chemosensory function of primary cilia regulates cholangiocyte migration,
      invasion and tumor growth.
AB  - : Cholangiocytes, the epithelial cells lining the biliary tree in the liver,
      express primary cilia that can detect several kinds of environmental signals and
      then transmit this information into the cell. We have previously reported that
      cilia are significantly reduced in cholangiocarcinoma (CCA) and that the
      experimental deciliation of normal cells induces a malignant-like phenotype with
      increased proliferation, anchorage independent growth, invasion and migration.
      Here, we tested the hypothesis that the chemosensory function of cholangiocyte
      primary cilia acts as a mechanism for tumor suppression. We found that in the
      presence of extracellular nucleotides, ciliary-dependent chemosensation of the
      nucleotides inhibited migration and invasion in normal ciliated cholangiocytes
      via a P2Y11 receptor and LKB1-PTEN-AKT dependent mechanism. In contrast, in
      normal deciliated cholangiocytes and CCA cells, the nucleotides induced the
      opposite effects, i.e. increased migration and invasion. As activation of LKB1
      via a ciliary dependent mechanism was required for the nucleotide-mediated
      inhibitory effects on migration and invasion, we attempted to activate LKB1
      directly, independent of ciliary expression, using the compound hesperidin methyl
      chalcone (HMC). We found that HMC induced activation of LKB1 in both ciliated and
      deciliated cells in vitro, resulting in the inhibition of migration and
      proliferation. Furthermore, using a rat syngeneic orthotopic CCA model, we found
      that HMC inhibited tumor growth in vivo. CONCLUSIONS: these findings highlight
      the importance of the chemosensory function of primary cilia for the control of
      migration and invasion, and suggest that by directly activating LKB1 and
      bypassing the need for primary cilia, it is possible to emulate this chemosensory
      function in CCA cells. These data warrant further studies for evaluating the
      possibility of using HMC as a novel therapy for CCA. This article is protected by
      copyright. All rights reserved.

PMID- 30299562
TI  - A Ligand-Enabled Palladium-Catalyzed Highly para-Selective Difluoromethylation of
      Aromatic Ketones.
AB  - A practical and highly para-selective C-H difluoromethylation of aromatic ketones
      has been developed by employing tetrakis(triphenylphosphine)palladium(0) as the
      catalyst and triphenylphosphine as the ligand. In addition to general aromatic
      ketones, this transformation was compatible with bioactive compounds and well
      known drugs, such as oxybenzone, ketoprofen, zaltoprofen, and propafenone.
      Moreover, a mechanistic study revealed that a palladium intermediate coordinated
      by a carbonyl group promotes highly para-selective difluoromethylation.

PMID- 30299563
TI  - Prognostic role of baseline 18 F-FDG PET/CT parameters in MALT lymphoma.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent lymphoma with
      good prognosis and variable fluorine-18 fluorodeoxyglucose (18 F-FDG) avidity.
      Many possible prognostic factors have been investigated with controversial
      results, but the possible prognostic role of 18 F-FDG positron emission
      tomography/computed tomography (PET/CT) remains unclear. Our aim was to evaluate
      the prognostic impact of qualitative and semiquantitative baseline PET/CT
      parameters on outcome of MALT lymphoma. We retrospectively enrolled 161 patients
      with histologically confirmed MALT lymphoma who underwent 18 F-FDG PET/CT before
      any treatment. PET images were qualitatively and semiquantitatively analyzed by
      measuring the maximum standardized uptake value body weight (SUVbw), lean body
      mass (SUVlbm), body surface area (SUVbsa), metabolic tumor volume (MTV), and
      total lesion glycolysis (TLG). The Kaplan-Meier method was used to estimate the
      progression-free survival (PFS) and overall survival (OS) times. Cox regression
      models were performed to determine the relation between PET/CT features and OS
      and PFS. Ninety-eight patients had positive 18 F-FDG PET/CT showing 18 F-FDG
      uptake (mean SUVbw, 10.1; SUVlbm, 7.2; SUVbsa, 2.7; MTV, 88.8; and TLG, 526); the
      remaining 63 were not 18 F-FDG avid. 18 F-FDG avidity was significantly
      correlated with tumor size and Ki-67 score. Relapse/progression of disease
      occurred in 47 patients with an average time of 40.2 months; death occurred in 12
      patients with an average of 59 months. At a median follow-up of 62 months, median
      PFS and OS were 52 and 62 months, respectively. Advanced tumor stage and
      extragastric site were demonstrated to be independent prognostic factors for PFS,
      while only tumor stage for OS. Instead, PET/CT parameters were not related to
      survival, despite positive correlation at univariate analysis between MTV and TLG
      with PFS and positive PET/CT with PFS and OS. In conclusion, a 61% rate of PET
      avidity in biopsy-confirmed MALT lymphoma was found, and it was correlated with
      tumor size and Ki-67 score. Only tumor stage and localization were independently
      correlated with PFS and OS.

PMID- 30299565
TI  - Computational insight into excited states of the ring-opening radicals from the
      pyrolysis of furan biofuels.
AB  - The low-lying valence excited states and Rydberg states of the radical species
      from the ring-opening reactions in pyrolysis of furan biofuels have been
      determined by extensive density functional theory and sophisticated wave function
      theory calculations. The radicals 1-C4 H5 O-2, 2-furylCH2 , and 4-C6 H7 O with
      the delocalized pi-type single electron are predicted to be most stable among the
      reactive species here for furan, 2-methyfuran, and 2,5-dimethylfuran,
      respectively. Predicted vertical transition energies by TD-CAM-B3LYP show good
      agreement with those by CASPT2. Some among the electronic excitations to low
      lying states can take place in the visible light region, and they may be involved
      in the combustion process. Further surface hopping dynamics simulations on the
      excited states of the most stable ring-opening radical 1-C4 H5 O-2 of furan as an
      example reveal that 89.9% sampling trajectories at the initial excited state of
      22 A"(pi1 pi*2 ) decay to the 12 A'(n1 pi*2 ) state within an average of 384 fs,
      and then 81.2% trajectories at the 12 A' state go to the ground state within an
      average of 114 fs. At the end of the simulation for 1000 fs, 18.8% trajectories
      still stay on the excited states of 22 A" and 12 A', suggesting that the reactive
      radicals in the ground state are mainly responsible for the combustion chemistry
      of furan biofuels. (c) 2018 Wiley Periodicals, Inc.

PMID- 30299564
TI  - Facile Activation of Homoatomic sigma Bonds in White Phosphorus and Diborane by a
      Diboraallene.
AB  - Metal-free activation of homoatomic E-E sigma bonds (E=P, B) in white phosphorus
      (P4 ) and bis(catecholato)diboron (B2 cat2 ) with a 1,2-diboraallene 1 is
      reported. The 1:1 and 1:2 reactions of P4 with 1 afford Bn P4 cages (2: n=2, 3:
      n=4), whereas a stoichiometric mixture of 1 and B2 cat2 undergoes homonuclear
      catenation through the addition of the B-B sigma bond of B2 cat2 across the B=B
      double bond of 1 (i.e. diboration), which leads to the formation of a tetraborane
      (4) featuring a B4 chain.

PMID- 30299566
TI  - Ex vivo evaluation of the efficacy of canine fresh-frozen plasma thawed using a
      microwave plasma defroster.
AB  - BACKGROUND: Commercial microwave plasma defrosters (MPDs) are used globally in
      human medicine to safely thaw fresh-frozen plasma (FFP), but this technology has
      never been tested in a veterinary setting. This study was undertaken to assess
      the efficacy of a commercial MPD for the rapid thawing of canine FFP. STUDY
      DESIGN: Twenty-three units (twelve 120 mL and eleven 240 mL) of canine FFP were
      thawed using an MPD. Time-to-thaw and pre- and postthawing temperatures of the
      units were measured. Clotting factor activities (factors II, V, VII, VIII, IX, X,
      and von Willebrand factor), fibrinogen concentrations, prothrombin times, and
      activated partial thromboplastin times were measured. KEY FINDINGS: The evaluated
      MPD effectively thaws plasma quickly for both 120 mL units (2.7 +/- 0.08 min) and
      240 mL units (3.9 +/- 0.15 min) while maintaining clinically relevant activities
      of clotting factors and fibrinogen concentration. While some measurements of
      factor VIII activity fell below the reference interval, none fell below 40%. One
      240 mL unit had von Willebrand factor activity <70%. There was no evidence of
      excessively heated plasma to indicate a safety concern. SIGNIFICANCE: The MPD
      evaluated in this study provides a useful means to rapidly thaw canine FFP for
      correction of factor-deficient coagulopathy.

PMID- 30299567
TI  - Nonsurgical management of traumatic pneumoperitoneum in a cat.
AB  - OBJECTIVE: To describe the nonsurgical management of a cat with traumatic
      pneumoperitoneum. CASE SERIES SUMMARY: A 4-year-old cat was presented following
      vehicular polytrauma. Thoracic radiographs revealed 4 rib fractures, a scapular
      fracture, and pneumothorax. Abdominal ultrasound revealed a small volume of free
      abdominal fluid. Computed tomography showed a mild pneumoretroperitoneum and a
      pneumoperitoneum in the region of the porta hepatis. The cat was managed
      conservatively with close monitoring. Exploratory laparotomy was not pursued
      given patient stability and static serial imaging studies revealing no
      indications for surgical intervention. After 6 days, the pneumoperitoneum was no
      longer detectable. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge,
      this is the first report of successful nonsurgical management of traumatic
      pneumoperitoneum in a cat.

PMID- 30299568
TI  - Determining prognosis in canine sepsis by bedside measurement of cell-free DNA
      and nucleosomes.
AB  - OBJECTIVE: To investigate the use of plasma cell-free DNA (cfDNA) and nucleosome
      concentrations as prognostic biomarkers in canine sepsis. DESIGN: Prospective,
      observational cohort study conducted from June 2015 to February 2016. SETTING:
      University teaching hospital. ANIMALS: Forty-five dogs with sepsis, 10 dogs with
      nonseptic systemic inflammatory response syndrome (nSIRS), and 15 healthy
      controls were consecutively enrolled and followed to hospital discharge. Patients
      were eligible for enrollment if they met >=2 SIRS criteria and had a documented
      or highly suspected bacterial infection. Dogs <3 kg or with a known coagulopathy
      were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute Patient
      Physiology and Laboratory Evaluation scores (APPLE) were calculated and outcomes
      recorded. Plasma cfDNA was measured using a benchtop fluorimeter. Plasma
      nucleosome concentrations were determined by ELISA. Plasma nucleosome and cfDNA
      concentrations in dogs with sepsis or nSIRS were compared to those of healthy
      controls and cfDNA concentrations in septic dogs with and without bacteremia were
      compared. Associations between cfDNA concentrations and nucleosomes, leukocyte
      count, neutrophil count, and APPLE scores were evaluated. For septic dogs, cfDNA
      concentrations relative to neutrophil count and nucleosome concentrations in
      survivors and nonsurvivors were compared. Alpha was set at 0.05. cfDNA
      concentrations were significantly higher in dogs with sepsis or nSIRS compared to
      healthy controls (P < 0.0001 and P = 0.0034, respectively). Nucleosome
      concentrations were significantly higher in dogs with sepsis compared to healthy
      controls (P = 0.007). There was limited association between cfDNA and nucleosome
      concentrations (rs  = 0.266), and no association between cfDNA concentration and
      leukocyte count, neutrophil count, and APPLEfull scores. Concentrations of cfDNA
      were positively correlated with APPLEfast score (rs  = 0.335, P = 0.025);
      however, cfDNA concentrations were significantly higher in dogs with bacteremia
      (P = 0.0299). In dogs with sepsis, cfDNA concentrations relative to neutrophil
      count were significantly higher in nonsurvivors than in survivors (P = 0.008).
      CONCLUSIONS: In dogs with sepsis, high cfDNA concentrations relative to
      neutrophil count are associated with nonsurvival. Point-of-care cfDNA measurement
      may aid identification of bacteremia.

PMID- 30299569
TI  - Use of two complementary new molecular techniques, next-generation sequencing and
      droplet digital PCR, for diagnosis of an F8 gene deletion and subsequent carrier
      analysis in a family with haemophilia A: A Case Report.

PMID- 30299570
TI  - Tumor targeting with 99m Tc radiolabeled peptides: Clinical application and
      recent development.
AB  - Targeting overexpressed receptors on the cancer cells with radiolabeled peptides
      has become very important in nuclear oncology in the recent years. Peptides are
      small and have easy preparation and easy radiolabeling protocol with no side
      effect and toxicity. These properties made them a valuable tool for tumor
      targeting. Based on the successful imaging of neuroendocrine tumors with 111 In
      octreotide, other receptor-targeting peptides such as bombesin (BBN),
      cholecystokinin/gastrin analogues, neurotensin analogues, glucagon-like peptide
      1, and RGD peptides are currently under development or undergoing clinical
      trials. The most frequently used radionuclides for tumor imaging are 99m Tc and
      111 In for single-photon emission computed tomography and 68 Ga and 18 F for
      positron emission tomography imaging. This review presents some of the 99m Tc
      labeled peptides, with regard to their potential for radionuclide imaging of
      tumors in clinical and preclinical application.

PMID- 30299571
TI  - In vitro hemolysis of stored units of canine packed red blood cells.
AB  - BACKGROUND: Hemolysis is an important quality parameter of packed red blood cells
      (pRBCs) that is used to assess the cellular integrity of stored blood units.
      According to human standards, hemolysis at the end of storage must not exceed 1%,
      as otherwise it may be responsible for decreased transfusion effectiveness and
      acute life-threatening reactions. OBJECTIVES: This prospective study was designed
      to evaluate the hemolysis of canine pRBCs stored in an additive solution
      containing adenine, dextrose, mannitol, and sodium chloride, and to assess its
      associations with storage time, duration of the collection process, collection
      disturbances, and with the final volume and PCV of the pRBCs units. METHODS: One
      hundred eighty pRBCs units were collected from canine donors. Hemolysis of the
      pRBCs units was determined immediately after processing (t = 0). The units were
      then stored and retested (t = 1) either before administration (during weeks 2, 3,
      4, 5, or 6 of storage) or at the end of the storage period (42 d) if not used.
      RESULTS: Mean hemolysis at t = 0 was 0.09% (SD 0.06) and increased during
      storage, at a more pronounced rate from the 5th (mean values of 0.52%, SD 0.29)
      to the 6th week (1.2%, SD 0.72). Almost 51% of the units with 36-42 days of shelf
      life showed more than 1% hemolysis. Disturbances in the collection process, the
      volume of the whole blood units, and the volume of stored pRBCs units or their
      PCV were not related to pRBCs hemolysis. CONCLUSIONS: According to human blood
      bank recommendations regarding acceptable hemolysis, canine pRBCs stored for more
      than 35 days should be tested to ensure <1% hemolysis prior to administration.

PMID- 30299572
TI  - Advances in the Ongoing Battle against the Consequences of Peripheral Nerve
      Injuries.
AB  - A number of constraints to the full recovery of a peripheral nerve injury are
      being fought with a battery of novel promising tools. Anat Rec, 301:1606-1613,
      2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30299573
TI  - The Centrality of the Peripheral Nerves: The Anatomical Record Showcases New
      Findings on Regeneration of Peripheral Nerves in our Latest Thematic Papers
      Issue.

PMID- 30299574
TI  - Multiple roles and diverse regulation of the Ras/cAMP/protein kinase A pathway in
      Candida albicans.
AB  - Candida albicans is a major fungal pathogen of humans, causing both superficial
      and life-threatening systemic infections in immunocompromised people. The
      conserved Ras/cAMP/PKA pathway plays a key role in regulating multiple traits
      important for the virulence of C. albicans such as cell growth, yeast-hyphal
      transition, white-opaque switching, sexual reproduction and biofilm development.
      Diverse external signals influence cell physiology by activating this signaling
      pathway. The key components of the Ras/cAMP/PKA pathway include two Ras GTPases
      (Ras1 and Ras2), an adenylyl cyclase (Cyr1, also known as Cdc35), two cyclic
      nucleotide phosphodiesterases (Pde1 and Pde2) and the catalytic (Tpk1 and Tpk2)
      and regulatory (Bcy1) subunits of PKA kinase. Activation of this pathway
      dramatically alters the gene expression profile via several transcription
      factors, leading to the activation of specific biological processes. Here, we
      review the progress made in the past two decades to elucidate the molecular
      mechanisms by which the Ras/cAMP/PKA pathway senses diverse environmental cues
      and controls specific cellular responses and its connection with other signaling
      pathways in C. albicans.

PMID- 30299575
TI  - A dermatoscopic portrait of morphological changes of vulvar melanosis over time.

PMID- 30299576
TI  - Analysis of volatile components in Dalbergia cochinchinensis Pierre by a
      comprehensive two-dimensional gas chromatography with mass spectrometry method
      using a solid-state modulator.
AB  - Volatile components in Dalbergia cochinchinensis Pierre were analysed using a
      comprehensive two-dimensional gas chromatography with mass spectrometry method
      featuring a new solid-state modulator. Compared to one-dimensional gas
      chromatography, the number of detected peaks were significantly increased. A
      total of 45 major compounds were identified in this study and the forward and
      reverse match factors of these compounds were both above 800. The results showed
      that the volatile components in Dalbergia cochinchinensis Pierre were primarily
      aldehyde and ketone compounds such as benzaldehyde, cinnamaldehyde, 4-chromanone,
      1-(2-hydroxyphenyl)ethanone and acetophenone. In addition, a semi-quantitative
      analysis was conducted to determine the contents of the detected compounds based
      on peak area percentage. Moreover, the repeatability of the comprehensive two
      dimensional gas chromatography-mass spectrometry analysis in this study was quite
      satisfactory with relative standard deviations less than 12.7% for intraday and
      17.3% for interday measurements.

PMID- 30299577
TI  - Complete response to pembrolizumab after initial progress in a patient with
      metastatic uveal melanoma.

PMID- 30299578
TI  - Multiple Sources for Sertoli Cells and Two Sertoli Phenotypes in the Adult
      Elasmobranch Testis: Insight from Two Species Belonging to Different Orders.
AB  - Findings presented here for the chondrichthyans Prionace glauca and Isurus
      oxyrinchus show that the assembly of the spermatocyst and it's attached
      collecting duct are seamlessly connected developmental phenomena. The cyst's
      somatic cell component (i.e., Sertoli cells, SCs) and the duct's constituent
      cells derive both from a common precursor cell type (typically a large oblong
      cell) found among the A-spermatogonia in the folliculogenic region. Novel
      findings show that the co-developing collecting duct itself serves also as a
      source of either normal-looking or basophilic atypical SCs (aSCs), depending on
      whether the duct-cyst transition remains mitotically active and open, or is
      sealed. The aSCs arise from accumulating slender basophilic cells at the duct
      cyst interface after which the newly formed cyst is sealed. Quantitative analysis
      of the latter in P. glauca revealed a correlation between the appearance of this
      aSC in immature cysts and the degenerated testicular condition that displays a
      gradient of multinucleate cell (MNC) death among spermatogonial cysts. Findings
      seem to implicate these aSCs in the life-death balance in mature spermatogonial
      cohorts downstream in the spermatogenic sequence, rather than in newly formed
      cysts that exhibit low rates of apoptosis. Photomicrographs of developing
      spermatogonial cysts showing several aSCs interspersed among cytoplasmically
      linked spermatogonia that are proliferating or have died, seem to suggest that
      these small SCs may be involved in confining MNC death to a given cyst region
      under conditions of subthreshold levels of apoptosis such as to ensure cyst
      recovery in immature spermatogonial cysts. Anat Rec, 301:1944-1954, 2018. (c)
      2018 Wiley Periodicals, Inc.

PMID- 30299579
TI  - Nail clipping with onychomycosis and surprise clue to the diagnosis of nail unit
      melanoma.

PMID- 30299580
TI  - The Plant Journal has introduced optional double-blind peer review.

PMID- 30299581
TI  - Correction.

PMID- 30299582
TI  - Regulation of diurnal growth: phytochrome interacting factor 5 is degraded by the
      E3 ubiquitin ligase CUL4COP 1- SPA.

PMID- 30299583
TI  - Synthesis and biological evaluation of genistein-O-alkylamine derivatives as
      potential multifunctional anti-Alzheimer agents.
AB  - A series of genistein derivatives were synthesized and evaluated as
      multifunctional anti-Alzheimer agents. The results showed that these derivatives
      had significant acetylcholinesterase (AChE) inhibitory activity; compound 5a
      exhibited the strongest inhibition to AChE with an IC50 value (0.034 MUM) much
      lower than that of rivastigmine (6.53 MUM). A Lineweaver-Burk plot and molecular
      modeling study showed that compound 5a targeted both the catalytic active site
      and the peripheral anionic site of AChE. These compounds also showed potent
      peroxy scavenging activity and metal-chelating ability. The compounds did not
      show obvious effect on HepG2 and PC12 cell viability at the concentration of 100
      MUM. Therefore, these genistein derivatives can be utilized as multifunctional
      agents for the treatment of AD.

PMID- 30299584
TI  - Activation of transient receptor potential vanilloid 3 channel (TRPV3) aggravated
      pathological cardiac hypertrophy via calcineurin/NFATc3 pathway in rats.
AB  - Cardiac hypertrophy is a compensatory response to mechanical stimuli and
      neurohormonal factors, ultimately progresses to heart failure. The proteins of
      some transient receptor potential (TRP) channels, Ca2+ -permeable nonselective
      cation channel, are highly expressed in cardiomyocytes, and associated with the
      occurrence of cardiac hypertrophy. Transient receptor potential vanilloid 3
      (TRPV3) is a member of TRP, however, the functional role of TRPV3 in cardiac
      hypertrophy remains unclear. TRPV3 was elevated in pathological cardiac
      hypertrophy, but not in swimming exercise-induced physiological cardiac
      hypertrophy in rats. TRPV3 expression was also increased in Ang II-induced
      cardiomyocyte hypertrophy in vitro, which was remarkably increased by carvacrol
      (a nonselective TRPV channel agonist), and reduced by ruthenium red (a
      nonselective TRPV channel antagonist). Interestingly, we found that activated
      TRPV3 in Ang II-induced cardiomyocyte hypertrophy was accompanied with increasing
      intracellular calcium concentration, promoting calcineurin, and phosphorylated
      CaMKII protein expression, and enhancing NFATc3 nuclear translocation. However,
      blocking or knockdown of TRPV3 could inhibit the expressions of calcineurin,
      phosphorylated CaMKII and NFATc3 protein by Western blot. In conclusion, the
      activation of TRPV3 aggravated pathological cardiac hypertrophy through
      calcineurin/NFATc3 signalling pathway and correlated with the protein expression
      levels of calcineurin, phosphorylated CaMKII and NFATc3, revealing that TRPV3
      might be a potential therapeutic target for cardiac hypertrophy.

PMID- 30299586
TI  - Cytology techniques for minimally invasive molecular autopsies: An opportunity
      not to be missed.

PMID- 30299585
TI  - Altered VEGF Signaling Leads to Defects in Heart Tube Elongation and
      Omphalomesenteric Vein Fusion in Quail Embryos.
AB  - Formation of the endocardial and myocardial heart tubes involves precise cardiac
      progenitor sorting and tissue displacements from the primary heart field to the
      embryonic midline-a process that is dependent on proper formation of conjoining
      great vessels, including the omphalomesenteric veins (OVs) and dorsal aortae.
      Using a combination of vascular endothelial growth factor (VEGF) over- and under
      activation, fluorescence labeling of cardiac progenitors (endocardial and
      myocardial), and time-lapse imaging, we show that altering VEGF signaling results
      in previously unreported myocardial, in addition to vascular and endocardial
      phenotypes. Resultant data show: (1) exogenous VEGF leads to truncated
      endocardial and myocardial heart tubes and grossly dilated OVs; (2) decreased
      levels of VEGF receptor 2 tyrosine kinase signaling result in a severe abrogation
      of the endocardial tube, dorsal aortae, and OVs. Surprisingly, only slightly
      altered myocardial tube fusion and morphogenesis is observed. We conclude that
      VEGF has direct effects on the VEGF receptor 2-bearing endocardial and
      endothelial precursors, and that altered vascular morphology of the OVs also
      indirectly results in altered myocardial tube formation. Anat Rec, 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 30299587
TI  - Synthesis of Cytokinins via Enzymatic Arsenolysis of Purine Nucleosides.
AB  - This unit describes an effective method for the preparation of natural cytokinins
      and their synthetic derivatives based on enzymatic cleavage of the N-glycosidic
      bond of N6 -substituted adenosine or O6 -substituted inosine derivatives in the
      presence of purine nucleoside phosphorylase (PNP) and Na2 HAsO4 . The arsenolysis
      reaction is irreversible due to the hydrolysis of the resulting alpha-D-ribose-1
      arsenate. As a result, the desired products are formed in near-quantitative
      yields, as indicated by high-performance liquid chromatography (HPLC) analysis,
      and can easily be isolated. In the strategy used here, the ribose residue acts as
      a protective group. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30299588
TI  - Erratum.

PMID- 30299589
TI  - Reporting violent patient incidents.

PMID- 30299590
TI  - Short-term and long-term incidence of stroke in Takotsubo syndrome.

PMID- 30299591
TI  - Effectiveness and safety of rivaroxaban vs. warfarin in patients with non
      valvular atrial fibrillation and heart failure.
AB  - AIMS: Heart failure (HF) is a common co-morbidity in non-valvular atrial
      fibrillation (NVAF) patients and a potent risk factor for stroke, bleeding, and a
      decreased time-in-therapeutic range with warfarin. We assessed the real-world
      effectiveness and safety of rivaroxaban and warfarin in NVAF patients with co
      morbid HF. METHODS AND RESULTS: Using US Truven MarketScan Commercial and
      Medicare supplemental database claims data from 11/2011 to 12/2016, we identified
      oral anticoagulant (OAC)-naive NVAF patients with HF (International
      Classification of Diseases, 10th Revision codes of I50 or I09.81) and >=12 months
      of insurance coverage prior to the qualifying OAC dispensing. Rivaroxaban users
      (20 or 15 mg once daily) were 1:1 propensity score matched to warfarin users,
      with residual absolute standardized differences <0.1 being achieved for all
      covariates after matching. Patients were followed up until an event, OAC
      discontinuation/switch, insurance disenrolment, or end of follow-up. Rates
      [events per 100 person-years (PYs) of follow-up] for stroke or systemic embolism
      and major bleeding (using the Cunningham algorithm) were compared between the
      matched cohorts using Cox proportion hazard regression and reported as hazard
      ratios (HRs) with 95% confidence intervals (CIs). We matched 3418 rivaroxaban
      (32% receiving the reduced dose) and 3418 warfarin users with NVAF and HF with a
      median (interquartile range) available follow-up of 1.4 (0.6, 2.5) years. Median
      age was 74 (63, 82) years, and median CHA2 DS2 -VASc and HASBLED scores were 4
      (3, 5) and 2 (2, 3). Common HF medications included beta-blockers (64%),
      angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (62%),
      loop diuretics (46%), digoxin (11%), and aldosterone receptor antagonists (10%).
      The hazard of developing stroke or systemic embolism (0.98 events/100PY vs. 1.28
      events/100PY; HR = 0.82, 95% CI = 0.47-1.44), ischaemic stroke (0.70 events/100PY
      vs. 1.02 events/100PY; HR = 0.77, 95% CI = 0.41-1.46), or major bleeding (3.86
      events/100PY vs. 4.23 events/100PY; HR = 0.98, 95% CI = 0.73-1.31) was not found
      to be different between rivaroxaban and warfarin users. Intracranial haemorrhage
      was infrequent in both cohorts and numerically less with rivaroxaban (0.27
      events/100PY vs. 0.36 events/100PY; HR = 0.73, 95% CI = 0.25-2.08). CONCLUSIONS:
      Effectiveness and safety of rivaroxaban vs. warfarin are sustained in NVAF
      patients with co-morbid HF treated in routine practice. The general consistency
      between this real-world study and those from phase III randomized trial data of
      rivaroxaban should provide additional reassurance to clinicians regarding the use
      of rivaroxaban in NVAF patients with HF.

PMID- 30299592
TI  - Arterial Patterns of the Face in Camelidamorpha.
AB  - Arteries supplying the intermandibular, mental, masseteric, buccal, labial, and
      nasal regions of the face in selected species belonging to the suborder Tylopoda
      are described in this study. Analyses were conducted on a total of five species
      representing the family Camelidae based on 27 heads of cadaveric specimens, which
      were prepared by arterial injection with acetone-dissolved stained vinyl super
      chloride or stained latex LBS3060. Vascularization of regions of the face was
      formed by the facial, sublingual, mental, transverse facial, buccal, and
      infraorbital arteries. It was confirmed that the linguofacial trunk is absent in
      Camelidae. In turn, in camels the deep temporal artery descended in the common
      trunk with the transverse facial artery, while in llamas and alpacas it was a
      direct branch of the maxillary artery. It was shown that the pattern of facial
      arteries in Camelidamorpha exhibits specific traits for this clade and differs
      from the system of these arteries in other artiodactyls. The described specific
      character in arterial vascularization of the face not only expands the spectrum
      of morphological characteristics in Camelidae, but it also provides information
      which may prove useful for clinical purposes in veterinary practice. Anat Rec,
      2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30299593
TI  - Chondroitin Sulfate in Human Cutaneous Meissner and Pacinian Sensory Corpuscles.
AB  - Chondroitin sulfate is a glycosaminoglycan involved in maintaining the
      morphofunctional properties of the extracellular matrix in peripheral nerves, but
      its distribution in human sensory corpuscles is unknown despite the role of
      extracellular matrix in mechanotransduction and axonal guidance. In this study we
      used immunohistochemistry to analyze the distribution of chondroitin sulfate in
      human cutaneous Meissner and Pacinian corpuscles. Chondroitin sulfate expression
      was absent from Meissner corpuscles. In Pacinian corpuscles chondroitin sulfate
      was found associated to a CD34 positive endoneurial-related layer, interposed
      between the S100 protein positive inner core cells, and the vimentin positive
      inner core and outer core-capsule cells. Therefore, the intermediate
      CD34+/chondroitin sulfate+ intermediate layer present in Pacinian corpuscles
      isolates the neural segment of the corpuscles (axon and inner core) from the non
      neural segments (outer core and capsule). These results suggest a role of
      chondroitin sulfate in the proper axonal growth and guidance, within the neuronal
      compartment of the Pacinian corpuscles during development and reinnervation, can
      be hypothesized. Moreover, a role of CS in mechanotransduction cannot be ruled
      out. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30299594
TI  - Order in Disorder as Observed by the "Hydrophobic Cluster Analysis" of Protein
      Sequences.
AB  - Hydrophobic cluster analysis (HCA) is an original approach for protein sequence
      analysis, which provides access to the foldable repertoire of the protein
      universe, including yet unannotated protein segments ("dark proteome"). Foldable
      segments correspond to ordered regions, as well as to intrinsically disordered
      regions (IDRs) undergoing disorder to order transitions. In this review, how HCA
      can be used to give insight into this last category of foldable segments is
      illustrated, with examples matching known 3D structures. After reviewing the HCA
      principles, examples of short foldable segments are given, which often contain
      short linear motifs, typically matching hydrophobic clusters. These segments
      become ordered upon contact with partners, with secondary structure preferences
      generally corresponding to those observed in the 3D structures within the
      complexes. Such small foldable segments are sometimes larger than the segments of
      known 3D structures, including flanking hydrophobic clusters that may be critical
      for interaction specificity or regulation, as well as intervening sequences
      allowing fuzziness. Cases of larger conditionally disordered domains are also
      presented, with lower density in hydrophobic clusters than well-folded globular
      domains or with exposed hydrophobic patches, which are stabilized by interaction
      with partners.

PMID- 30299595
TI  - Pim-1 Expression in Rat Retina and its Changes after Optic Nerve Crush.
AB  - Pim-1 is a proto-oncogene which has been discovered to involve in cell
      proliferation, differentiation, and survival. In this study, we observed the
      expression of Pim-1 in neonatal and adult rat retina and the changes in rat
      retina following optic nerve crush (ONC) in order to explore the relationship
      between Pim-1 and the survival of retinal ganglion cells (RGC). We discovered
      that Pim-1 was distributed mainly in retinal pigment epithelial cells (RPE) and
      retinal ganglion cell layer (GCL) in normal newborn rats, and it appeared in RPE,
      cone rod cell layer and GCL in normal adult rats by immunohistochemistry. Our
      double immunofluorescent staining of Pim-1 and gamma-synuclein further confirmed
      that Pim-1 was localized in 80% of RGC. Moreover, we found that the amount of Pim
      1 mRNA and protein in adult rat retina was transiently increased after ONC and
      then decreased 2 weeks after ONC, and the expression level was lower than that of
      neonatal rat retina under all conditions. We also discovered that Pim-1
      expression in GCL detected by immunohistochemistry was upregulated at Day 1 and
      Day 3 after ONC, but downregulated at Day 14 after ONC when the survival of RGC
      was decreased and the apoptotic cells in GCL were increased by hematoxylin-eosin
      staining, immunohistochemistry, and TUNEL detection. We suggest that the
      overexpression of Pim-1 in the RGC is related to the optic nerve repair while the
      low expression of Pim-1 in RGC may be associated with apoptosis and weak
      intrinsic regeneration ability of RGC. Anat Rec, 301:1968-1976, 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 30299596
TI  - Introduction: Thematic Papers Issue on Peripheral Nerve Regeneration and Repair.
AB  - Injuries to the peripheral nerves result in loss of motor, sensory and autonomic
      functions in the denervated segments of the body, thus having strong impact in
      the quality of life of affected patients. Neurons are able to regenerate their
      injured axons in the peripheral nerves; however, the endogenous repair mechanisms
      usually do not allow for a satisfactory functional recovery, especially after
      severe nerve injuries. The interest on regeneration after peripheral nerve
      injuries has increased in the recent years due to the numerous advances derived
      from studies of neurobiology, cell therapy, and tissue engineering. This Thematic
      Papers Issue brings together a number of papers, authored by researchers in the
      field, which cover a wide spectrum of topics related to regeneration and repair
      of peripheral nerve injuries. The Issue proposal originated from the recent 4th
      International Symposium on Peripheral Nerve Regeneration (ISPNR2017) which was
      hosted by Xavier Navarro and the European Society for the Study of Peripheral
      Nerve Repair and Regeneration in Barcelona, Spain. Anat Rec, 301:1614-1617, 2018.
      (c) 2018 Wiley Periodicals, Inc.

PMID- 30299597
TI  - Generation and Biological Characteristics of a Mouse Model of Breast Cancer that
      Copresents with Diabetes Mellitus.
AB  - Both diabetes and breast cancer are common diseases worldwide, and diabetes is
      also linked to higher rates of breast cancer. Epidemiological data also indicate
      that diabetes may be one of the risk factors for breast cancer. However, the
      effect of diabetes on breast cancer progression in vivo is rarely reported. We
      established an ideal animal model of breast cancer using transgenic MMTV-PyMT
      mice, which spontaneously developed breast cancer. In this model, the animals
      copresented with diabetes mellitus, which allowed us to study the effect of high
      glucose on breast cancer. Compared with MMTV-PyMT mice without diabetes, MMTV
      PyMT mice with diabetes developed heavier tumors and exhibited greater tumor
      volumes. Furthermore, high glucose promoted the invasiveness and metastasis of
      breast cancer in MMTV-PyMT mice. This breast cancer model in which mice
      copresented with diabetes provides a useful tool to study the effect of diabetes
      on breast cancer. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30299598
TI  - Three-Dimensional Musculoskeletal Modeling of the Sauropodomorph Hind Limb: The
      Effect of Postural Change on Muscle Leverage.
AB  - The biomechanical constraints for life at massive size can be directly observed
      in the evolutionary history of sauropodomorph dinosaurs. Members of this lineage
      underwent a number of major postural transitions as they increased in size from
      relatively small bipedal dinosaurs to massive titanosaurs that include the
      largest terrestrial animals of all time. To better understand the impact of
      gigantic size on the biomechanics of sauropods, we used three-dimensional
      musculoskeletal modeling to investigate how hind limb musculature was affected,
      first by the development of a quadrupedal stance from a bipedal one, and later in
      the transition from a narrow-gauge to a wide-gauge stance. Muscle moment arms
      were measured in four sauropodomorph taxa: the bipedal basal sauropodomorph
      Plateosaurus engelhardti, the narrow-gauge diplodocid Diplodocus carnegii, the
      titanosauriform Giraffatitan brancai, and the wide-gauge titanosaur
      Diamantinasaurus matildae. In Plateosaurus, low moment arm leverage in the hip
      extensors and knee flexors and extensors was observed suggesting high-velocity
      movement for fast locomotion. A reduction in hip extensor leverage in
      Diamantinasaurus was found which suggests a reduced role for the hind limb in
      forward propulsion in titanosaurs. An increase in overall hip adductor leverage
      and leverage of adductors 1 and 2 in Diamantinasaurus, compared with other taxa
      studied, might relate to the development of a wide-gauge stance. High knee flexor
      extensor leverage in Giraffatitan but not Diamantinasaurus partially refutes the
      idea that broader femoral condyles in titanosauriforms increased knee torque
      production capabilities. Sauropodomorph postural changes clearly had an impact on
      the function and leverage of hind limb muscles. Anat Rec, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30299599
TI  - Enhancement of Vascular Smooth Muscle Contractility by Alterations of Membranous
      Architecture.
AB  - Plasma membrane (PM) of smooth muscle cells hosts channel molecules regulating
      the flow of various ions. An intact architecture of PM is essential to
      orchestrate proper channel functions in order to complete agonist-mediated
      contraction, which includes Ca2+ release from the sarcoplasmic reticulum (SR) to
      initiate contraction, and subsequent Ca2+ refilling into SR through PM to sustain
      muscle contraction. The Junctional Complex (JC), comprising of junctional SR, and
      its apposing PM and neighboring caveolae, provides a quasi-enclosed microdomain
      housing receptors as well as ion channels and also restricting ion diffusions
      into the cytosol so the cell achieves optimal performance. The spatial
      arrangement of the JC is believed to ensure an uninterrupted Ca2+ cycling route.
      Full understanding of the functional role of the JC is the key to elucidating the
      contractile mechanisms of vascular smooth muscle and the physiological function
      of vessel contraction. The JC can be further divided into two sub-divisions,
      namely the PM-SR and caveolar regions. Previously, we demonstrated the role of
      the PM-SR region in the initiation of muscle contraction using pharmacological
      tools on the inferior vena cava (IVC) of rabbit. In the current study, we further
      dissected the caveolar region using a cholesterol-disrupting agent to investigate
      the role of the caveolar region. We conclude that disruption of the caveolar
      region in rabbit IVC smooth muscle results in augmented muscle contraction in
      response to adrenergic stimulation and the altered Ca2+ signaling may underlie
      the augmented contractility. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30299601
TI  - [in process].

PMID- 30299602
TI  - [in process].

PMID- 30299603
TI  - [in process].

PMID- 30299600
TI  - Rationale and design of the EU-CERT-ICD prospective study: comparative
      effectiveness of prophylactic ICD implantation.
AB  - AIMS: The clinical effectiveness of primary prevention implantable cardioverter
      defibrillator (ICD) therapy is under debate. The EUropean Comparative
      Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable
      Cardioverter Defibrillators (EU-CERT-ICD) aims to assess its current clinical
      value. METHODS AND RESULTS: The EU-CERT-ICD is a prospective investigator
      initiated non-randomized, controlled, multicentre observational cohort study
      performed in 44 centres across 15 European Union countries. We will recruit 2250
      patients with ischaemic or dilated cardiomyopathy and a guideline indication for
      primary prophylactic ICD implantation. This sample will include 1500 patients at
      their first ICD implantation and 750 patients who did not receive a primary
      prevention ICD despite having an indication for it (non-randomized control
      group). The primary endpoint is all-cause mortality; the co-primary endpoint in
      ICD patients is time to first appropriate shock. Secondary endpoints include
      sudden cardiac death, first inappropriate shock, any ICD shock, arrhythmogenic
      syncope, revision procedures, quality of life, and cost-effectiveness. At
      baseline (and prior to ICD implantation if applicable), all patients undergo 12
      lead electrocardiogram (ECG) and Holter ECG analysis using multiple advanced
      methods for risk stratification as well as detailed documentation of clinical
      characteristics and laboratory values. Genetic biobanking is also organized. As
      of August 2018, baseline data of 2265 patients are complete. All subjects will be
      followed for up to 4.5 years. CONCLUSIONS: The EU-CERT-ICD study will provide a
      necessary update about clinical effectiveness of primary prophylactic ICD
      implantation. This study also aims for improved risk stratification and patient
      selection using clinical and ECG risk markers.

PMID- 30299604
TI  - [in process].

PMID- 30299605
TI  - [in process].

PMID- 30299606
TI  - [in process].

PMID- 30299607
TI  - [in process].

PMID- 30299608
TI  - [in process].

PMID- 30299610
TI  - [in process].

PMID- 30299609
TI  - [in process].

PMID- 30299611
TI  - [in process].

PMID- 30299613
TI  - [in process].

PMID- 30299612
TI  - [in process].

PMID- 30299614
TI  - [in process].

PMID- 30299615
TI  - [in process].

PMID- 30299616
TI  - [in process].

PMID- 30299617
TI  - [in process].

PMID- 30299619
TI  - [in process].

PMID- 30299620
TI  - [in process].

PMID- 30299618
TI  - [in process].

PMID- 30299621
TI  - [in process].

PMID- 30299622
TI  - [in process].

PMID- 30299623
TI  - [in process].

PMID- 30299624
TI  - [in process].

PMID- 30299625
TI  - [in process].

PMID- 30299626
TI  - [in process].

PMID- 30299627
TI  - [in process].

PMID- 30299628
TI  - Report as Presented to the LDA House of Delegates.

PMID- 30299629
TI  - Identity Theft - as Certain as Death and Taxes?

PMID- 30299630
TI  - ADEX as the Universal Cure for Dental Portability and Consistency.

PMID- 30299631
TI  - [Landmark events in the history of medicine to be commemorated in 2017].

PMID- 30299661
TI  - [Taxonomic Composition of Lake Baikal Bacterioneuston Communities].
AB  - The taxonomic composition of microbial communities of Lake Baikal surface
      microlayer was studied by pyrosequencing of the 16S rDNA amplicons. Statistically
      reliable differences were found between bacterioneuston of the shallow and deep
      water stations. The shallow station community was characterized by higher
      diversity than the deep-water one. While bacterioneuston communities were shown
      to be less diversethan the water column communities, their diversity was
      comparable to that of other biofilm associations. Microbial communities of Lake
      Baikal surface microlayer were shown to be similar to those of the water column
      in the composition of predominant phyla, while differing considerably at the
      genus level. Bacterioneuston of Lake Baikal was comparable to microbial
      communities of the surface microlayer of other freshwater basins, although it was
      characterized by high abundance of the Alphaproteobacteria and Verrucomicrobia.
      High abundance of photoheterotrophs compared to the water column communities of
      other freshwater basins was another distinctive feature of Lake Baikal
      bacterioneuston. Our results showed the Lake Baikal surface microlayer to be a
      specific microbial community with low species diversity and relatively high
      abundance of photoheterotrophic microorganisms.

PMID- 30299662
TI  - [Endophytic Yeasts in Leaf Galls].
AB  - Yeast abundance and species diversity of endophytic complexes in galls (cecidia)
      formed on the leaves of Salix fragilis, Salix caprea, Quercus robur, Tilia
      cordata, and Ulmus laevis and the epiphytic yeast communities of undamaged leaves
      of these plants were studied. Dynamics of yeast abundance in the galls was
      significantly different from that of the epiphytic yeast communities. Maximum
      numbers of endophytic yeastcells in the galls (up to 104 CFU/g) were comparable
      to abundance of epiphytic yeasts. A total of 14 species of endophytic yeasts were
      isolated from galls of different plants. Ascomycetous yeasts were found to
      predominate in the insect galls on willows and oak, while basidiomycetous yeasts
      dominated in mite galls on linden and elm, as well as on plant leaves. These
      results indicate that gall formation may be considered not only as abidirectional
      pathological process of the interaction between plants and invertebrates, but
      also as a process in which the endophytic microbial population of the galls plays
      an important role.

PMID- 30299663
TI  - Account of Prize-Questions.

PMID- 30299665
TI  - List of New Members of the Royal College of Physicians and Royal Society of
      Edinburgh.

PMID- 30299664
TI  - History of a Case in Which Singular Symptoms Occurred from the Swallowing of an
      Iron Nail, Which Remained in the Stomach for about Fifteen Months.

PMID- 30299666
TI  - Two Cases, Shewing That the Anterior Part of the Brain May Sustain Considerable
      Injury without a Fatal Consequence.

PMID- 30299667
TI  - Letter from Dr Richard Pearson of Birmingham, Respecting the Good Effects of
      Inspiring Vitriolic AEther in Cases of Phthisis Pulmonalis.

PMID- 30299668
TI  - Some Cases of Biliary Obstructions, from Calculi, Cured by Salivation.

PMID- 30299669
TI  - Account of the State of the Barometer, Thermometer, and Rain, at London and
      Edinburgh, during the Year 1795.

PMID- 30299671
TI  - Observations by Dr Withering on Pneumatic Medicine, Communicated in a Letter to
      Dr Duncan.

PMID- 30299670
TI  - The History of a Case Terminating Fatally from Swallowing a Plumb-Stone.

PMID- 30299672
TI  - Extract of a Letter from Mr George Kellie, Surgeon to His Majesty's Ship the
      Iris, Containing Some Observations on the Anatomy of the Shark.

PMID- 30299673
TI  - Account of the Good Effects, in the Cure of Diseases, Obtained in Bengal, from
      the Use of the Toon-Tree Bark.

PMID- 30299674
TI  - The History of a Singular Case of Diabetes Successfully Treated.

PMID- 30299675
TI  - A Case of Hydrocele Cured by Injection, Communicated to G. Pearson, M. D.

PMID- 30299676
TI  - Extract of a Letter to Dr Duncan, from Dr Brodbelt of Jamaica, Giving an Account
      of Some Observations and Experiments Made on the Gas Contained in the Air-Bladder
      of the Swordfish.

PMID- 30299677
TI  - A Case of Obstinate Constipation of the Bowels Cured by Calomel, Communicated to
      Dr Pearson.

PMID- 30299678
TI  - History of a Case of Cynanche, Attended with Symptoms of a High Degree of
      Putrescency, Where a Favourable Crisis Succeeded a Paroxysm of Furious Delirium.

PMID- 30299679
TI  - Account of the Effects Produced on the Human Body by the Internal Use of the
      Nitrous Acid, and of the Benefit Derived from It in the Cure of Diseases.

PMID- 30299680
TI  - Account of the Progress of Dr Beddoes's Pneumatic Institution at Bristol.

PMID- 30299681
TI  - Observations on the Epidemic Fever of Jamaica; with the History of a Remarkable
      Case Terminating Fatally, in Which a Great Quantity of Mercury Was Employed
      without Any Obvious Operation.

PMID- 30299682
TI  - History of a Case of the Epidemic Fever of Jamaica Terminating Successfully, in
      Which a Very Large Quantity of Mercury Was Employed without Any Obvious Operation
      during the Fever.

PMID- 30299683
TI  - Account of a Contagious Fever, Which Appeared in the 88th Regiment, in Jersey, in
      July 1797.

PMID- 30299684
TI  - History of a Case Terminating Fatally, from a Concretion Formed in the Bowels in
      Consequence of Swallowing the Stones of Fruit.

PMID- 30299685
TI  - Account of a Case, in Which a Fistula in Perinaeo Was Healed by the Introduction
      of a Seton.

PMID- 30299687
TI  - Extract of a Letter Respecting the Cow-Pox.

PMID- 30299686
TI  - Observations on the Pemphigus Major, with Two Cases.

PMID- 30299688
TI  - Letter from Dr Garnet, on the Use of the Oxygenated Muriat of Potash.

PMID- 30299690
TI  - List of Members Admitted during 1797, into the Royal Society, the Royal Colleges
      of Physicians and Surgeons, and Medical Faculty of the University of Edinburgh.

PMID- 30299689
TI  - Copy of a Letter from Mr David Paterson to the Navy Medical Board, on the Good
      Effects of Nitrous Vapour.

PMID- 30299692
TI  - Letter from Dr Guthrie of Petersburgh, Containing Various Articles of Medical
      Information Respecting Russia.

PMID- 30299691
TI  - Account of Some Discoveries of Mr Park in Africa.

PMID- 30299693
TI  - Official Directions to the Medical Practitioners Belonging to the French Army.

PMID- 30299694
TI  - Histories of Different Tetanic Complaints, in Which the Most Powerful Remedies
      Were Employed in Vain.

PMID- 30299695
TI  - Letter from Dr Cappe on the Internal Use of the Nitrat of Silver.

PMID- 30299696
TI  - Account of the Poisonous Effects of the Decoction of Certain Plants.

PMID- 30299697
TI  - Account of the State of the Thermometer, Barometer, and Rain, at London and
      Edinburgh, during the Year 1797.

PMID- 30299698
TI  - Letter from Dr Withering, Giving an Account of an Easy Method of Inhaling the
      Vapour of Volatile Substances.

PMID- 30299699
TI  - History of the Case of a Foetus Found in the Right Ovarium.

PMID- 30299700
TI  - Histories of Singular Cases of Ruptured Uterus and Vagina.

PMID- 30299701
TI  - History of a Singular Case in Midwifery, Where Delivery Was Effected by an
      Incision through the Vagina.

PMID- 30299702
TI  - Observations on the Duration and Course of Fever in Britain, and on the Efficacy
      of Medicine in Interrupting Its Course, and in Shortening Its Duration.

PMID- 30299703
TI  - A Letter from Dr D. G. Yates, Physician at Bedford, to Dr Duncan, Giving an
      Account of the Good Effects Obtained from a Combination of Calomel and Opium in
      Inflammatory Diseases; with Observations on the Effects Arising from Acetite of
      Copper, and on Some Other Important Subjects in the Practice of Medicine.

PMID- 30299704
TI  - Account of a Singular Case, in Which a Young Woman Was Cured of Loss of Speech by
      Burning with Moxa.

PMID- 30299705
TI  - Account of the Institution of a Society in London for the Extermination of the
      Small-Pox.

PMID- 30299706
TI  - Account of the Introduction of Vaccine Inoculation into the Isle of Mann.

PMID- 30299707
TI  - Notice of Dr Kinglake's Proposal of the Topical Use of Cold Water in Gout.

PMID- 30299709
TI  - Notice Respecting the New Regulations for the Studies and Graduations in Medicine
      in France, &c.

PMID- 30299708
TI  - History of the Case of a Man Who Discharged by the Anus a Portion of the
      Intestines, Full Fourteen Inches in Length.

PMID- 30299710
TI  - The History of a Recovery from a Singular Species of Hiccup, Which Had Subsisted
      for Several Months.

PMID- 30299711
TI  - Account of the Beneficial Effects of the Affusion of Cold Water in Typhus Fever.

PMID- 30299712
TI  - Case of a Gunshot Wound, with a Division of the Femoral Artery.

PMID- 30299713
TI  - History of a Singular Case of an Extra-Uterine Foetus Discharged by the Rectum.

PMID- 30299714
TI  - Observations on Bilious Disorders, Extracted from a Letter Dated from the River
      Ganges, in September 1770, to a Friend.

PMID- 30299715
TI  - History of a Remarkable Case of Diabetes, Treated in the Royal Infirmary of
      Edinburgh, and Extracted from the Records of That Hospital.

PMID- 30299716
TI  - Remarkable Cases of Convulsions, with Some Observations on the Haemorrhoea
      Petechialis, or Petechiae Sine Febre.

PMID- 30299717
TI  - History of a Considerable Wound of the Brain, Attended with Singular
      Circumstances.

PMID- 30299718
TI  - Notice of the Influenza 1803.

PMID- 30299719
TI  - Account of Gratuitous Vaccine Inoculation at the Public Dispensary of Edinburgh.

PMID- 30299720
TI  - ?

PMID- 30299721
TI  - Some Further Observations and Experiments on the Vaccine Inoculation.

PMID- 30299722
TI  - Case of Suppression of Urine and Stools, Occasioned by the Retroversion of the
      Uterus, Which Terminated Fatally.

PMID- 30299723
TI  - Case of Elisabeth Woodcock, Who Remained Buried in the Snow, without Food for
      Eight Days.

PMID- 30299724
TI  - Medical Histories.

PMID- 30299725
TI  - Observations on the Benefit Derived from the Application of Cold Water in
      Scarlatina Cynanchica.

PMID- 30299726
TI  - Case of Tetanus Cured by the Liberal Use of Wine.

PMID- 30299727
TI  - Observations on the Pemphigus Major of Sauvages.

PMID- 30299728
TI  - Observations on the Vaccine Inoculation.

PMID- 30299729
TI  - Sen. Examples of the Good Effects from the Use of the Hydrargyrus Muriatus Mitis
      in Croup.

PMID- 30299730
TI  - List of Members Admitted during 1799, into the Royal Society and the Royal
      Colleges of Physicians and Surgeons of Edinburgh.

PMID- 30299731
TI  - Epidemic Diseases among the Domestic Animals in America.

PMID- 30299732
TI  - Letter from Dr Yeats of Bedford, on the Effects of Nitric Vapour in Destroying
      Contagion.

PMID- 30299733
TI  - Plan of the Medical Repository.

PMID- 30299734
TI  - Observations on the Cow-Pox.

PMID- 30299735
TI  - Case of Retropulsed Gonorrhoea, Succeeded by a Severe Affection of the Eyes,
      Terminating Favourably.

PMID- 30299736
TI  - Observations of Dr Archer on the Use of the Polygala Seneca in Croup.

PMID- 30299737
TI  - A Singular Variety of the Chorea Sancti Viti, Considerably Relieved by the Use of
      the Argentum Nitratum.

PMID- 30299738
TI  - Table of the Number of Students at the University of Edinburgh, during the Last
      Ten Years of the Eighteenth Century.

PMID- 30299739
TI  - Case of Uterine Haemorhage, Where the Placenta Was Expelled Four Hours before the
      Birth of the Child.

PMID- 30299740
TI  - Observations on Digitalis.

PMID- 30299741
TI  - Letter from Dr Matthew Guthrie of Petersburg, Containing Various Articles of
      Medical Information.

PMID- 30299743
TI  - Speculations Concerning the Perspirable Fluids of the Human Body.

PMID- 30299742
TI  - Singular Case of Obstruction to the Execretion of Urine.

PMID- 30299744
TI  - Case, in Which an Inverted Uterus Was Successfully Extirpated.

PMID- 30299745
TI  - Letter from Dr G. G. Brown of Bath, with an Account of the Good Effects of the
      External Application of Cold in Madness.

PMID- 30299746
TI  - Case of a Wounded Kidney.

PMID- 30299748
TI  - Account of the State of the Thermometer, Barometer, and Rain, at London and
      Edinburgh, during 1798.

PMID- 30299747
TI  - Case of a Severe Wound of the Tongue, Threatening Locked-Jaw, Terminating
      Successfully.

PMID- 30299749
TI  - Sequel of the Case of Extrauterine Foetus, Partly Voided through an Abscess in
      the Abdomen.

PMID- 30299750
TI  - Identity of Galvanism and Electricity.

PMID- 30299751
TI  - Observations on Bilious Disorders.

PMID- 30299752
TI  - History of a Fracture of the Skull, with Very Considerable Injury to the Brain,
      Terminating in Complete Recovery, without Any Operation.

PMID- 30299754
TI  - Extract of a Letter Written by Dr James S. Stringham of New York, to Dr Duncan,
      Concerning Vaccine Inoculation.

PMID- 30299755
TI  - Account of Gratuitous Vaccine Inoculation at the Public Dispensary of Edinburgh.

PMID- 30299753
TI  - History of a Case of Imperforated Hymen.

PMID- 30299756
TI  - Account of a Case in Which the Anus Was Wanting, Successfully Cured.

PMID- 30299758
TI  - Observations on a Case of Zona, on the Cow-Pox, and on Angina Pectoris.

PMID- 30299757
TI  - Account of the Benefit Derived from Vaccine Inoculation, in Combating a Singular
      Disease of the Right Arm.

PMID- 30299759
TI  - Observations on the Use of the Muriat of Barytes in Scrofulous Affections of the
      West Indies, and in a Singularly Painful Disease Arising from the Bite of a
      Negro.

PMID- 30299760
TI  - Letter from Mr R. W. Taylor, Surgeon, London, to Dr Duncan Senior, Giving an
      Account of Two Cases of Vaccina, Attended with Eruptions.

PMID- 30299761
TI  - Extract of a Letter from Dr Pearson of London, on Mr Chenevix's Mode of Preparing
      James's Powder by Precipitation; with Notices Respecting Vaccina, &c.

PMID- 30299763
TI  - Notice of Recent Discoveries Respecting Galvanism.

PMID- 30299762
TI  - Letter from Mr Young, Relating His Own Case, in Which an Enlarged Spleen Was
      Cured by the Actual Cautery.

PMID- 30299764
TI  - On the Use of the Cuprum Ammoniacale in the Cure of Epilepsy: Communicated in a
      Letter from Dr William Batt, Genoa, to Dr Duncan Junior.

PMID- 30299766
TI  - Account of the Epidemic Disease Which Raged in Cadiz in Summer and Autumn 1800,
      with the Method of Treatment.

PMID- 30299765
TI  - Observations on Cow-Pox.

PMID- 30299767
TI  - Account of a Deception with Respect to Vaccine Inoculation.

PMID- 30299768
TI  - Extract of a Letter from Dr Hall to Dr Duncan Senior, Containing Farther
      Observations on the Cow-Pox.

PMID- 30299769
TI  - Galvanic Piles.

PMID- 30299770
TI  - Observations on a Case of Diabetes Insipidus, with an Account of Some Experiments
      on the Urine.

PMID- 30299772
TI  - State of the Thermometer, Barometer, and Rain, at London and Edinburgh, during
      the Year 1800.

PMID- 30299771
TI  - Singular Termination of a Case of Enteritis.

PMID- 30299773
TI  - Extract of a Letter to Dr Duncan Senior, from Mr James Anderson Senior, Surgeon
      in Edinburgh, Concerning the Use of the Mild Muriat of Quicksilver in the Cure of
      Croups.

PMID- 30299775
TI  - Return of Effective Men and Deaths in the 72d Regiment, from Oct. 1785 to Oct.
      1788, While Stationed at Tanjore on the Coromandel Coast, by Mr Wood, Surgeon to
      the Regiment.

PMID- 30299774
TI  - Cases of Chorea Sancti Viti, Terminating Successfully under the Use of Zinc.

PMID- 30299776
TI  - Extract of a Letter from Mr John Livingston, Surgeon of the Cirencester East
      Indiaman, to Dr George Kellie, Containing Some Observations on the Benefit
      Derived from Compression by the Tourniquet, in the Removal of Rheumatic Pains.

PMID- 30299777
TI  - Extract of a Letter from Dr John Rook of Montpellier Old Works, to the Honourable
      Fr. R. Brodbelt of Spanish-Town, Giving an Account of the Success of Vaccine
      Inoculation in Some Districts of Jamaica.

PMID- 30299778
TI  - Letter from Dr Paisley of Madras on the Bilious Disorders of That Climate.

PMID- 30299779
TI  - Account of Diseases of the 88th Regiment, during Their Passage to India, and at
      Bombay, from December 1798 Till June 1800.

PMID- 30299780
TI  - List of Members Admitted, during the Year 1801, into the Royal College of
      Physicians of Edinburgh.

PMID- 30299781
TI  - Cases of Vaccine Disease.

PMID- 30299782
TI  - Letter from Mr Wife of Maryport Respecting the Use of the Oleum Tritici.

PMID- 30299783
TI  - Dr Campbell, Argyleshire.

PMID- 30299784
TI  - Extract of a Letter from Dr Pearson to Dr Duncan with Regard to the Vaccina.

PMID- 30299786
TI  - Letter to Dr Pearson from Dr Barry in Cork, Respecting the Cow-Pock in Ireland.

PMID- 30299785
TI  - History of a Case of Angina Polyposa or Croup, Which Terminated Successfully
      under the Use of Calomel and Emetics.

PMID- 30299787
TI  - Account of a Method Employed in Bengal, for the Cure of the Cutaneous Disease,
      Commonly Known by the Name of Ring-Worms, the Herpes Serpigo of Sauvages, by
      Means of Cassunda Vinegar.

PMID- 30299789
TI  - Account of the Institution in London for the Inoculation of the Vaccine Pock.

PMID- 30299788
TI  - Account of the Employment of Very Large Quantities of the AErugo AEris, Exhibited
      Internally to Horses, with a View to the Cure of Glanders.

PMID- 30299790
TI  - Dr Wilson, Montrose.

PMID- 30299792
TI  - Dr Kennedy, Inverness.

PMID- 30299791
TI  - Letter from Mr Alexander Williamson to Dr Duncan Respecting the Inoculation of
      the Vaccine Disease.

PMID- 30299793
TI  - Dr Melville, St Andrew's.

PMID- 30299794
TI  - Cases of Yaws and Leprosy Treated with Nitrous Acid and Oxygenated Muriate of
      Potash.

PMID- 30299795
TI  - Remarks on a Case of Inversio Uteri, Terminating Fatally.

PMID- 30299796
TI  - A Short Account of the Epidemic Polypus at Grenada in 1790.

PMID- 30299797
TI  - Observations on Cold Applications to the Head in Cases of Insanity.

PMID- 30299798
TI  - History of a Case of Convulsions during the Latter Months of Pregnancy, with
      Practical Remarks on Convulsions during Pregnancy and Labour.

PMID- 30299799
TI  - List of Members Admitted during the Year 1800, into the Royal Society, and Royal
      Colleges of Physicians and Surgeons of Edinburgh.

PMID- 30299800
TI  - Account of Singular Effects of the Peruvian Bark.

PMID- 30299801
TI  - Account of the Institution at York for Vaccine Inoculation.

PMID- 30299803
TI  - Account of the Introduction of Vaccine Inoculation into Paris.

PMID- 30299802
TI  - Observations on the Use of the Argentum Nitratum in Chorea Sancti Viti.

PMID- 30299804
TI  - Letter to Dr Duncan from Dr Anderson of Leith Respecting Vaccine Inoculation.

PMID- 30299806
TI  - Notice from Dr Pearson to His Correspondents Concerning the Vaccina.

PMID- 30299805
TI  - Letters on the Yellow Fever, Addressed to Joseph Wilson, Esq; American Consul.

PMID- 30299807
TI  - Letter from Dr George Kellie, Physician to the British Prisoners at Valenciennes,
      Respecting the Extract of the Rhus Radicans.

PMID- 30299808
TI  - A Curious Case of Spasmodic Affection of the Face, Cured by the Oxygenated
      Muriate of Potash, by the Same.

PMID- 30299809
TI  - Cases of Patients Treated at the Dispensary and Lunatic Asylum of Montrose.

PMID- 30299810
TI  - State of the Thermometer, Barometer, and Rain, at London and Edinburgh, during
      the Year 1799.

PMID- 30299811
TI  - Account of a Singularly Fatal Epidemic among Cats.

PMID- 30299812
TI  - Account of Gratuitous Vaccine Inoculation at the Public Dispensary of Edinburgh.

PMID- 30299813
TI  - Account of the Introduction of Vaccine Inoculation into America.

PMID- 30299814
TI  - Observations and Experiments on the Electricity of Animals.

PMID- 30299815
TI  - Account of a Woman Who Remained in a Coal-Pit for near Twenty Days, without Food.

PMID- 30299817
TI  - Observations on the Influenza, as It Appeared in the Isle of Man in Spring 1803.

PMID- 30299816
TI  - Observations on the Means of Destroying Contagion.

PMID- 30299818
TI  - Observations on a Case of Diabetes Mellitus: With the History of the Morbid
      Appearances Which Were Discovered on Dissection.

PMID- 30299819
TI  - Three Cases of Hydrocephalus Chronicus; with Some Remarks on That Disease.

PMID- 30299820
TI  - Letter from the Rev. Mr Monteath, Respecting the Progress of Vaccination in
      Renfrewshire.

PMID- 30299821
TI  - Observations on the Influenza, as It Appeared at Bristol in the Year 1803.

PMID- 30299822
TI  - Members Admitted into the Royal Society, Edin.

PMID- 30299823
TI  - Notice Respecting a New Periodical Work, to Succeed the Annals, under the Title
      of The Edinburgh Medical and Surgical Journal.

PMID- 30299825
TI  - Common Culinary Salt Recommended for Fumigation, in Place of Nitre.

PMID- 30299824
TI  - Notice Respecting a New Edition of the Edinburgh Pharmacopoeia.

PMID- 30299826
TI  - Observations by Mr Braithwaite on the Utility of Oxygenated Muriatic Acid in the
      Cure of Scarlet Fever.

PMID- 30299827
TI  - Notice Respecting the Conclusion of Dr Duncan's Annals of Medicine.

PMID- 30299828
TI  - Members Admitted into the Royal College of Surgeons, Edinburgh.

PMID- 30299829
TI  - Address Transmitted to the Established Clergy of Scotland on the Subject of
      Vaccine Inoculation.

PMID- 30299830
TI  - Letter from the Rev. Mr Duguid, Giving an Account of the Success of Vaccination
      in Orkney.

PMID- 30299831
TI  - Notice Respecting an Improved Edition of Dr Duncan Junior's Edinburgh New
      Dispensatory.

PMID- 30299832
TI  - Report of the Committee of the House of Commons on Dr James Carmichael Smyth's
      Method of Destroying Contagion by Means of Nitrous Fumigation.

PMID- 30299833
TI  - Extract of a Letter from Dr Duncan Senior to Dr Smyth on the Benefit of Nitrous
      Fumigation at Edinburgh.

PMID- 30299835
TI  - Notice Respecting a General Index to Dr Duncan's Medical Commentaries and Annals.

PMID- 30299834
TI  - History of a Singular Affection of the Right Leg, Accompanied with Symptomatic
      Epilepsy, Which Was Cured in the Royal Infirmary of Edinburgh, by the Use of
      Galvanism.

PMID- 30299836
TI  - A Letter from Dr Robert Sproat of Belize, in the Bay of Honduras, Dated 2d
      October 1802, to Captain Chichester Macdonell, Respecting the Managua Bark of
      South America.

PMID- 30299837
TI  - Account of the Progress of the Vaccine Institution at Edinburgh.

PMID- 30299838
TI  - A Letter to Dr Thomas Beddoes, Physician at Bristol, Respecting the Influenza at
      Edinburgh, in Spring 1803.

PMID- 30299839
TI  - Members Admitted Since 1802 into the Royal College of Physicians, Edinburgh.

PMID- 30299840
TI  - Account of Two Cases of Diabetes Mellitus, with Remarks.

PMID- 30299841
TI  - Three Treatises, on the Brain, the Eye, and the Ear.

PMID- 30299842
TI  - The History of a Case, in Which, after a Complete Inversion of the Uterus, a
      Favourable Termination Took Place.

PMID- 30299843
TI  - Reports, Principally Concerning the Effects of the Nitrous Acid in the Venereal
      Disease.

PMID- 30299844
TI  - The History of a Case in Which a Tapeworm Was Discharged from the Stomach, on the
      Use of an Emetic.

PMID- 30299845
TI  - Abstract from a Publication by Count Berchtold, Respecting Mr Baldwin's Method of
      Preventing and Curing the Plague, Successfully Employed in Egypt.

PMID- 30299846
TI  - Circular Letter from Dr Beddoes of Bristol, Respecting the Use of the Nitrous
      Acid in the Venereal Disease.

PMID- 30299847
TI  - Observations on Mr Baynton's Method of Treating Ulcers of the Legs.

PMID- 30299848
TI  - Account of the Benefit Derived from the Use of Arsenic in the Hooping-Cough.

PMID- 30299849
TI  - Letter from Dr John Wilson on the Good Effects of the Argentum Nitratum in the
      Cure of Epilepsy.

PMID- 30299850
TI  - Account, by Dr George Mossman, of Epileptic Fits Being Arrested by Extending the
      Jaws, and Keeping the Teeth Asunder.

PMID- 30299852
TI  - The History of an Inveterate Case of Tinea Capitis, Successfully Treated by the
      Application of an Adhesive Paste.

PMID- 30299851
TI  - Account of a Memoir, by Citizen Bonhomme, on the Cure of Rachitis, by the
      External Use of Alkaline Lotions, and the Internal Use of Phosphate of Lime.

PMID- 30299853
TI  - Extraordinary Case of an Extra-Uterine Foetus, Voided through an Abscess in the
      Cavity of the Abdomen.

PMID- 30299854
TI  - The History of a Long Continued Case of Obstipation Terminating Fatally, with an
      Account of the Appearances on Dissection.

PMID- 30299855
TI  - Letters from Mr George Kellie, Surgeon of the Leopard, to His Father Mr Kellie,
      Surgeon, Leith, Respecting the Effects of the Nitrous Acid in the Cure of
      Syphilis.

PMID- 30299856
TI  - An Inquiry into the Nature and Causes of the Great Mortality among the Troops at
      St Domingo.

PMID- 30299858
TI  - Account of the State of the Barometer, Thermometer, and Rain, at London and
      Edinburgh, in the Year 1796.

PMID- 30299857
TI  - Observations on the Medical Effects of Compression by the Tourniquet.

PMID- 30299860
TI  - Letter from Count Rumford to the Royal Society of London, Respecting the
      Institution of a Prize-Medal for Important Discoveries Concerning Light or Heat.

PMID- 30299859
TI  - Report by Dr William Wright, Physician to the Army, Respecting the Diseases Most
      Common among the Troops in the West Indies.

PMID- 30299861
TI  - History of a Singular Case of Petechiae Sine Febre, Accompanied with Excessive
      Hoemorrhagies, Terminating Favourably under the Use of the Vitriolic Acid.

PMID- 30299862
TI  - Universal History of Medicine and Physics.

PMID- 30299863
TI  - Observations by Dr J. Harness, on the Use of the Gastric Fluid of Graminivorous
      Animals in the Cure of Ulcers.

PMID- 30299864
TI  - Observations on the Seats and Causes of Diseases, Illustrated by the Dissections
      of the Late Professor Morgagni.

PMID- 30299865
TI  - History of a Case in Which a Wound of the Head, with a Considerable Depression of
      the Cranium, Terminated in Complete Recovery, without Any Operation.

PMID- 30299866
TI  - The History of a Case of Venereal Ulcer, Effectually Cured by the Topical Use of
      an Arsenical Corrosive Application.

PMID- 30299867
TI  - Observation, by Mr David Macliesh, on the Cure of the Intermittent Fevers of
      Corsica.

PMID- 30299868
TI  - The Plait, the Yellow Spot, and the Transparent Portion of the Retina of the Eye.

PMID- 30299869
TI  - History of a Case Terminating Successfully, after Amputation Was Performed at the
      Shoulder-Joint.

PMID- 30299870
TI  - History of a Case of Imperforate Hymen, Successfully Removed by Operation.

PMID- 30299871
TI  - Letter from Mr Stephen Hammick, on the Benefit Obtained from the External Use of
      Hops in the Cure of Large Sordid Ulcers.

PMID- 30299873
TI  - Account of the Deliveries, Births, Deaths, &c. in the British Lying-In-Hospital
      of London, from Its Institution.

PMID- 30299872
TI  - A Treatise on the Yellow Fever, as It Appeared in Dominica in 1793 and 1796.

PMID- 30299874
TI  - Letter from Dr Thomas Garnett, Respecting the Benefit Derived from the Oxygenated
      Muriate of Potash Employed Employed as a Medicine.

PMID- 30299875
TI  - Chemist to the Ordnance, the Result of the Trials of Various Acids, and Some
      Other Susbtances, in the Cure of Lues Venerea.

PMID- 30299876
TI  - Account of Indian Serpents Collected on the Coast of Coromandel.

PMID- 30299877
TI  - Hints for a System of Diagnostics, Communicated to Reflecting Physicians.

PMID- 30299878
TI  - The History of a Remarkable Case of Typhus Fever, Immediately Succeeded by
      Measles, Terminating Successfully.

PMID- 30299879
TI  - Letter from Mr James M'Gregor, Confirming Dr Smyth Carmichael's Method of
      Destroying Febrile Contagion.

PMID- 30299880
TI  - A Case of Phthisis Pulmonanalis Completely Cured from the Patient Breathing
      Mephitic Air.

PMID- 30299881
TI  - Summary of Two Papers Published in the Exeter Essays, Respecting Rain, Heat, and
      Light.

PMID- 30299883
TI  - [Sulfate-Reducing Bacteria in the Microbial Community of Acidic Drainage from a
      Gold Deposit Tailing Storage].

PMID- 30299882
TI  - [Structure of Epiphytic Bacterial Communities of Weeds].
AB  - Dynamics of the taxonomic structure of epiphytic bacterial communities of the
      rhizosphere and phyllosphere of seven weed species was studied. The major types
      of isolated organisms were identified using phenotypic and molecular biological
      approaches. Dispersion analysis revealed that the ontogenesis stage and plant
      organ were the factors with the greatest effect on the taxonomic structure of the
      communities. The dominantmicroorganisms of weeds were similar to those of
      cultivated plants. The minor components revealed in the spectra of bacterial
      communities of weeds belonged to poorly studied genera of chemolithotrophic
      proteobacteria.

PMID- 30299885
TI  - [A Low-Molecular Mass Antimicrobial Peptide from Trichoderma cf. aureoviride
      Rifai VKM F-4268D].

PMID- 30299884
TI  - European Society of Endocrinology Clinical Practice Guidelines on the management
      of adrenocortical carcinoma in adults, in collaboration with the European Network
      for the Study of Adrenal Tumors
AB  - Adrenocortical carcinoma (ACC) is a rare and in most cases steroid hormone
      producing tumor with variable prognosis. The purpose of these guidelines is to
      provide clinicians with best possible evidence-based recommendations for clinical
      management of patients with ACC based on the GRADE (Grading of Recommendations
      Assessment, Development and Evaluation) system. We predefined four main clinical
      questions, which we judged as particularly important for the management of ACC
      patients and performed systematic literature searches: (A) What is needed to
      diagnose an ACC by histopathology? (B) Which are the best prognostic markers in
      ACC? (C) Is adjuvant therapy able to prevent recurrent disease or reduce
      mortality after radical resection? (D) What is the best treatment option for
      macroscopically incompletely resected, recurrent or metastatic disease? Other
      relevant questions were discussed within the group. Selected Recommendations: (i)
      We recommend that all patients with suspected and proven ACC are discussed in a
      multidisciplinary expert team meeting. (ii) We recommend that every patient with
      (suspected) ACC should undergo careful clinical assessment, detailed endocrine
      work-up to identify autonomous hormone excess and adrenal-focused imaging. (iii)
      We recommend that adrenal surgery for (suspected) ACC should be performed only by
      surgeons experienced in adrenal and oncological surgery aiming at a complete en
      bloc resection (including resection of oligo-metastatic disease). (iv) We suggest
      that all suspected ACC should be reviewed by an expert adrenal pathologist using
      the Weiss score and providing Ki67 index. (v) We suggest adjuvant mitotane
      treatment in patients after radical surgery that have a perceived high risk of
      recurrence (ENSAT stage III, or R1 resection, or Ki67 >10%). (vi) For advanced
      ACC not amenable to complete surgical resection, local therapeutic measures (e.g.
      radiation therapy, radiofrequency ablation, chemoembolization) are of particular
      value. However, we suggest against the routine use of adrenal surgery in case of
      widespread metastatic disease. In these patients, we recommend either mitotane
      monotherapy or mitotane, etoposide, doxorubicin and cisplatin depending on
      prognostic parameters. In selected patients with a good response, surgery may be
      subsequently considered. (vii) In patients with recurrent disease and a disease
      free interval of at least 12 months, in whom a complete resection/ablation seems
      feasible, we recommend surgery or alternatively other local therapies.
      Furthermore, we offer detailed recommendations about the management of mitotane
      treatment and other supportive therapies. Finally, we suggest directions for
      future research.

PMID- 30299886
TI  - MECHANISMS IN ENDOCRINOLOGY: Bone marrow adiposity and bone, a bad romance?
AB  - Bone marrow adipocytes (BMA-) constitute an original and heterogeneous fat depot
      whose development appears interlinked with bone status throughout life. The
      gradual replacement of the haematopoietic tissue by BMA arises in a well-ordered
      way during childhood and adolescence concomitantly to bone growth and continues
      at a slower rate throughout the adult life. Importantly, BM adiposity quantity is
      found well associated with bone mineral density (BMD) loss at different skeletal
      sites in primary osteoporosis such as in ageing or menopause but also in
      secondary osteoporosis consecutive to anorexia nervosa. Since BMA and osteoblasts
      originate from a common mesenchymal stem cell, adipogenesis is considered as a
      competitive process that disrupts osteoblastogenesis. Besides, most factors
      secreted by bone and bone marrow cells (ligands and antagonists of the WNT/beta
      catenin pathway, BMP and others) reciprocally regulate the two processes.
      Hormones such as oestrogens, glucocorticoids, parathyroid and growth hormones
      that control bone remodelling also modulate the differentiation and the activity
      of BMA. Actually, BMA could also contribute to bone loss through the release of
      paracrine factors altering osteoblast and/or osteoclast formation and function.
      Based on clinical and fundamental studies, this review aims at presenting and
      discussing these current arguments that support but also challenge the
      involvement of BMA in the bone mass integrity.

PMID- 30299887
TI  - MECHANISMS OF ENDOCRINOLOGY: Endocrinology of opioids
AB  - The use of opioids has grown substantially over the past two decades reaching the
      dimensions of a global epidemic. These drugs have effects on multiple levels of
      the endocrine system through mechanisms which are still not fully elucidated, and
      awareness of their endocrine sequelae is vital for all specialists prescribing or
      managing patients on them. Hypogonadism is the most well-recognised consequence
      of opioid use (prevalence 21-86%) which, however, may remain undiagnosed with
      potential adverse outcomes for the patients. Although less frequent, cortisol
      deficiency can also be found. Furthermore, there is a negative impact on bone
      health (with reduced bone mineral density and increased fracture risk) and
      occasionally hyperprolactinaemia, whereas the clinical significance of
      alterations in other hormones remains to be clarified. Discontinuation or
      reduction of the opioid and, in cases of chronic pain, consideration of
      alternative therapies for pain relief are potential management options. Hormonal
      replacement, especially when the above measures are not practically feasible,
      needs to be considered. Further studies are needed to clearly establish the
      prevalence of hormonal abnormalities with various regimes, doses and routes of
      opioids and to address reliably the long-term benefits and risks of hormonal
      treatment in patients on opioids. Until evidence-based, safe and cost-effective
      clinical guidelines become available, periodical assessment of the gonadal and
      adrenal function (particularly when relevant clinical manifestations are present)
      and evaluation of the bone health status are advised.

PMID- 30299889
TI  - MANAGEMENT OF ENDOCRINE DISEASE: Critical review of the evidence underlying
      management of glucocorticoid-induced hyperglycaemia
AB  - Glucocorticoids are frequently prescribed to patients with a wide range of
      inflammatory and autoimmune diseases. The semi-synthetic glucocorticoid
      prednisolone is most commonly prescribed and in two main patterns. Prednisolone
      is prescribed short term at medium-high doses to treat an acute inflammatory
      illness or long term at lower doses to attenuate chronic inflammatory disease
      progression. In hospitalized patients with acute prednisolone-induced
      hyperglycaemia, there is a distinct circadian pattern of glucose elevation, which
      occurs predominantly in the afternoon and evening. As a morning dose of isophane
      insulin has a pharmacokinetic pattern that matches this pattern of glucose
      elevation, treatment comprising a basal dose of morning isophane insulin in
      combination with short-acting insulin boluses is generally recommended. However,
      evidence is lacking that isophane-based basal bolus insulin is more efficacious
      than other insulin regimens. In outpatients, low-dose prednisolone causes a small
      increase in post glucose-load glucose concentration but no change in overall
      glycaemic control as measured by glycosylated haemoglobin. If treatment is
      indicated, metformin has been shown to be effective and may attenuate other
      adverse effects of long-term prednisolone therapy. Further studies are necessary
      in order to identify factors underlying the variability in response to insulin
      therapy and clinical benefits of treatment in hospitalized patients with
      prednisolone-induced hyperglycaemia. In outpatients prescribed low-dose
      prednisolone, the cardiovascular risk associated with postprandial hyperglycaemia
      and efficacy of hypoglycaemic therapies should be evaluated in future randomized
      clinical trials.

PMID- 30299888
TI  - GENETICS IN ENDOCRINOLOGY: Approaches to molecular genetic diagnosis in the
      management of differences/disorders of sex development (DSD): position paper of
      EU COST Action BM 1303 'DSDnet'
AB  - The differential diagnosis of differences or disorders of sex development (DSD)
      belongs to the most complex fields in medicine. It requires a multidisciplinary
      team conducting a synoptic and complementary approach consisting of thorough
      clinical, hormonal and genetic workups. This position paper of EU COST (European
      Cooperation in Science and Technology) Action BM1303 'DSDnet' was written by
      leading experts in the field and focuses on current best practice in genetic
      diagnosis in DSD patients. Ascertainment of the karyotpye defines one of the
      three major diagnostic DSD subclasses and is therefore the mandatory initial
      step. Subsequently, further analyses comprise molecular studies of monogenic DSD
      causes or analysis of copy number variations (CNV) or both. Panels of candidate
      genes provide rapid and reliable results. Whole exome and genome sequencing (WES
      and WGS) represent valuable methodological developments that are currently in the
      transition from basic science to clinical routine service in the field of DSD.
      However, in addition to covering known DSD candidate genes, WES and WGS help to
      identify novel genetic causes for DSD. Diagnostic interpretation must be
      performed with utmost caution and needs careful scientific validation in each DSD
      case.

PMID- 30299890
TI  - Prognostic relevance of proliferation-related miRNAs in pancreatic neuroendocrine
      neoplasms
AB  - Objective: Pancreatic neuroendocrine neoplasms (PanNENs) are rare tumors arising
      from the endocrine pancreas; however, their prognosis differs significantly upon
      their proliferative state, which is characterized by histopathological grading.
      MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene
      expression. Our aim was to identify miRNAs with altered expression upon
      proliferation which can be used as prognostic biomarkers in PanNENs. Methods:
      MiRNA expression profiles of 40 PanNENs were downloaded from Gene Expression
      Omnibus and were reanalyzed upon tumor grades (discovery cohort). Results of the
      reanalysis were confirmed by qRT-PCR analysis of five miRNAs on an independent
      validation cohort of 63 primary PanNEN samples. Cox proportional hazards survival
      regression models were fit for both univariate and multivariate analysis to
      determine the miRNAs' effect on progression-free and overall survival. Results:
      Nineteen miRNAs displayed differential expression between tumor grades. The
      altered expression of three out of five chosen miRNAs was successfully validated;
      hsa-miR-21, hsa-miR-10a and hsa-miR-106b were upregulated in more proliferative
      PanNENs compared to Grade 1 tumors. In univariate analysis, higher expression of
      tissue hsa-miR-21, hsa-miR-10a and hsa-miR-106b of primary PanNENs predicted
      worse progression-free and overall survival; however, multivariate analysis only
      confirmed the expression of hsa-miR-21 as an independent prognostic factor.
      Conclusions: The expression of hsa-miR-106b, hsa-miR-10a and especially hsa-miR
      21 has prognostic relevance regarding progression-free and overall survival in
      patients with PanNENs.

PMID- 30299891
TI  - Comorbidities in patients with non-functioning pituitary adenoma: influence of
      long-term growth hormone replacement
AB  - Background: Patients with hypopituitarism have an increased mortality. The aim of
      this study was to investigate comorbidities including cerebral infarction, type 2
      diabetes mellitus (T2DM) and malignant tumors in patients with non-functioning
      pituitary adenomas (NFPA) with and without growth hormone replacement therapy
      (GHRT). Methods: Observational cohort study in patients with NFPA within the
      western region of Sweden. Subjects were identified through the National Patient
      Registry and followed between 1987 and 2014. Patient records were reviewed and
      standardized incidence ratios (SIRs) with 95% CIs for comorbidities were
      calculated. Results: In total, 426 patients were included, 206 with GHRT and 219
      without. Median (range) follow-up time for patients with and without GHRT was
      12.2 (0-24) and 8.2 (0-27) years, respectively. Mean +/- s.d. BMI was 28.5 +/-
      4.5 and 26.5 +/- 4.4 for patients with and without GHRT, respectively (P <
      0.001). Incidence of cerebral infarction was increased (SIR: 1.39; 95% CI: 1.03
      1.84; P = 0.032), with no difference between patients with and without GHRT. SIR
      for T2DM in patients not receiving GHRT was increased (1.65; 1.06-2.46; P =
      0.018), whereas the incidence in patients receiving GHRT was not (0.99; 0.55
      1.63; P = 0.99). The incidence of malignant tumors was not increased, either in
      patients with or without GHRT. Conclusion: The incidence of cerebral infarction
      is increased in patients with NFPA irrespective of GHRT. Patients without GHRT
      had an increased risk of T2DM, whereas patients with GHRT had a normal incidence
      of T2DM, despite having higher BMI. Incidence of malignant tumors was not
      increased. Thus, long-term GHRT seems to be safe regarding risk of comorbidities.

PMID- 30299893
TI  - ?

PMID- 30299892
TI  - ?

PMID- 30299894
TI  - Change in serum 25-hydroxyvitamin D and parallel change in depressive symptoms in
      Dutch older adults
AB  - Objectives: Previous prospective studies on the association between vitamin D
      status and depression used a single 25-hydroxyvitamin D (25(OH)D) measurement. We
      investigated the association between change in serum 25(OH)D and parallel change
      in depressive symptoms over time in Dutch older adults. Design: A population
      based, prospective study in two cohorts of older men and women from the
      Longitudinal Aging Study Amsterdam. Methods: Serum 25(OH)D concentrations were
      determined at two time points: in 1995/1996 and 13 years later in the older
      cohort (aged 65-88y, n = 173) and in 2002/2003 and 6 years later in the younger
      cohort (55-65 years, n = 450). At these time points, depressive symptoms were
      measured with the Center for Epidemiologic Studies Depression scale (CES-D).
      Associations were tested by multiple linear regression analyses. Results: During
      follow-up, serum 25(OH)D concentrations increased in 32.4% of the older cohort
      and in 69.8% of the younger cohort. In the older cohort, change in 25(OH)D was
      not associated with change in CES-D score. In the younger cohort, no associations
      were observed in participants with higher baseline 25(OH)D concentrations (>58.6
      nmol/L), but in those with lower baseline 25(OH)D concentrations, an increase in
      25(OH)D was associated with a decrease in CES-D score (adjusted B per 10 nmol/L
      25(OH)D increase: -0.62 (95% CI: -1.17, -0.07)).

PMID- 30299897
TI  - ?

PMID- 30299896
TI  - ?

PMID- 30299895
TI  - Preserved insulin secretion and kidney function in recipients with functional
      pancreas grafts 1 year after transplantation: a single-center prospective
      observational study
AB  - Objective: Successful simultaneous pancreas and kidney transplantation (SPK) or
      pancreas transplantation alone (PTA) restores glycemic control. Diabetes and
      impaired kidney function are common side effects of immunosuppressive therapy.
      This study addresses glucometabolic parameters and kidney function during the
      first year. Methods: We examined 67 patients with functioning grafts (SPK n = 30,
      PTA n = 37) transplanted between September 2011 and November 2016 who underwent
      repeated oral glucose tolerance tests (OGTTs) 8 and 52 weeks after
      transplantation. Another 19 patients lost their graft the first year post
      transplant and 28 patients did not undergo repeated OGTTs and could not be
      studied. All patients received ATG induction therapy plus tacrolimus,
      mycophenolate and prednisolone. Glomerular filtration rate was measured before
      and 8 and 52 weeks after transplantation by serum clearance methods. Results:
      From week 8 to 52 after transplantation, mean fasting glucose decreased (SPK: 5.4
      +/- 0.7 to 5.1 +/- 0.8 mmol/L, PTA: 5.4 +/- 0.6 to 5.2 +/- 0.7 mmol/L; both P <
      0.05), and also 120-min post-OGTT glucose (SPK: 6.9 +/- 2.9 to 5.7 +/- 2.2
      mmol/L; P = 0.07, PTA: 6.5 +/- 1.7 to 5.7 +/- 1.2 mmol/L; P < 0.05). Fasting C
      peptide levels also decreased (SPK: 1500 +/- 573 to 1078 +/- 357 pmol/L, PTA:
      1210 +/- 487 to 1021 +/- 434 pmol/L, both P < 0.005). Measured GFR decreased from
      enlistment to 8 weeks post transplant in PTA patients (94 +/- 22 to 78 +/- 19
      mL/min/1.73 m2; P < 0.005), but did not deteriorate from week 8 to week 52 (SPK:
      55.0 +/- 15.1 vs 59.7 +/- 11.3 ml/min/1.73 m2; P = 0.19, PTA: 76 +/- 19 vs 77 +/-
      19 mL/min/1.73 m2; P = 0.74). Conclusion: Glycemic control and kidney function
      remain preserved in recipients with functioning SPK and PTA grafts 1 year after
      transplantation.

PMID- 30299898
TI  - ?

PMID- 30299900
TI  - ?

PMID- 30299901
TI  - ?

PMID- 30299915
TI  - ?

PMID- 30299902
TI  - Characterization of fibroblast growth factor 1 in obese children and adolescents
AB  - Background: Fibroblast growth factor 1 (FGF1) can regulate glucose and lipid
      metabolism in obese mice. Serum FGF1 has increased in type 2 diabetes mellitus
      adults and correlated with BMI. This study aimed to indicate conventional weight
      loss effects on FGF1 in obese children and adolescents. Materials and Methods:
      Clinical and metabolic parameters of 88 lean and obese individuals (ages 5-15
      years) and 39 obese individuals followed with 6 months of lifestyle intervention
      were collected. Serum FGF1 levels were detected through enzyme-linked
      immunosorbent assays. Results: FGF1 levels were increased in obese individuals.
      Serum FGF1 levels were significantly correlated with BMI and waist circumferences
      (r = 0.377, P = 0.012; r = 0.301, P = 0.047, respectively). Multivariate stepwise
      linear regression analyses showed that FGF1 levels were significantly correlated
      with HbA1c and HOMA-IR (beta = 0.371, P = 0.008; beta = 0.323, P = 0.021,
      respectively). Weight loss (2.3 +/- 0.1 kg) was accompanied by a significant
      reduction of circulating FGF1 levels (7.2 +/- 0.4 pg/mL). Changes in FGF1 were
      significantly correlated with changes in fasting glucose, HOMA-IR and low-density
      lipoprotein cholesterol (beta = 0.277, P = 0.020; beta = 0.474, P < 0.001; beta =
      0.320, P = 0.008, respectively). Conclusion: FGF1 levels were increased in obese
      individuals. Serum FGF1 levels were significantly correlated with BMI and waist
      circumferences (r = 0.377, P = 0.012; r = 0.301, P = 0.047, respectively).
      Multivariate stepwise linear regression analyses showed that FGF1 levels were
      significantly correlated with HbA1c and HOMA-IR (beta = 0.371, P = 0.008; beta =
      0.323, P = 0.021, respectively). Weight loss (2.3 +/- 0.1 kg) was accompanied by
      a significant reduction of circulating FGF1 levels (7.2 +/- 0.4 pg/mL). Changes
      in FGF1 were significantly correlated with changes in fasting glucose, HOMA-IR
      and low-density lipoprotein cholesterol (beta = 0.277, P = 0.020; beta = 0.474, P
      < 0.001; beta = 0.320, P = 0.008, respectively).

PMID- 30299899
TI  - Radiation exposure of adrenal vein sampling: a German Multicenter Study
AB  - Objective: Adrenal vein sampling (AVS) represents the current diagnostic standard
      for subtype differentiation in primary aldosteronism (PA). However, AVS has its
      drawbacks. It is invasive, expensive, requires an experienced interventional
      radiologist and comes with radiation exposure. However, exact radiation exposure
      of patients undergoing AVS has never been examined. Design and Methods: We
      retrospectively analyzed radiation exposure of 656 AVS performed between 1999 and
      2017 at four university hospitals. The primary outcomes were dose area product
      (DAP) and fluoroscopy time (FT). Consecutively the effective dose (ED) was
      approximately calculated. Results: Median DAP was found to be 32.5 Gy*cm2 (0.3
      3181) and FT 18 min (0.3-184). The calculated ED was 6.4 mSv (0.1-636).
      Remarkably, values between participating centers highly varied: Median DAP ranged
      from 16 to 147 Gy*cm2, FT from 16 to 27 min, and ED from 3.2 to 29 mSv. As main
      reason for this variation, differences regarding AVS protocols between centers
      could be identified, such as number of sampling locations, frames per second and
      the use of digital subtraction angiographies. Conclusions: This first systematic
      assessment of radiation exposure in AVS not only shows fairly high values for
      patients, but also states notable differences among the centers. Thus, we not
      only recommend taking into account the risk of radiation exposure, when referring
      patients to undergo AVS, but also to establish improved standard operating
      procedures to prevent unnecessary radiation exposure.

PMID- 30299917
TI  - A Series of Metal-Organic Frameworks for Selective CO2 Capture and Catalytic
      Oxidative Carboxylation of Olefins.
AB  - Three new lanthanide-based metal-organic frameworks (Ln-MOFs), namely MOF-590, 
      591, and -592 constructed from a tetratopic linker, benzoimidephenanthroline
      tetracarboxylic acid (H4BIPA-TC), were synthesized under solvothermal conditions
      and fully characterized. All of the new MOFs exhibit three-dimensional
      frameworks, which adopt unprecedented topologies in MOF field. Gas adsorption
      measurements of MOF-591 and -592 revealed good adsorption of CO2 (low pressure,
      at room temperature) and moderate CO2 selectivity over N2 and CH4. Consequently,
      breakthrough experiments illustrated the separation of CO2 from binary mixture of
      CO2 and N2 with the use of MOF-592. Accordingly, MOF-592 revealed the selective
      CO2 capture effectively without any loss in performance after three cycles.
      Moreover, MOF-590, -591, and -592 showed to be catalytically active in the
      oxidative carboxylation of styrene and CO2 for a one-pot synthesis of styrene
      carbonate under mild conditions (1 atm CO2, 80  degrees C, and without solvent).
      Among the new materials, MOF-590 revealed a remarkable efficiency with
      exceptional conversion (96%), selectivity (95%), and yield (91%).

PMID- 30299916
TI  - Follicular thyroid lesions: is there a discriminatory potential in the
      computerized nuclear analysis?
AB  - Background: Computerized image analysis seems to represent a promising diagnostic
      possibility for thyroid tumors. Our aim was to evaluate the discriminatory
      diagnostic efficiency of computerized image analysis of cell nuclei from
      histological materials of follicular tumors. Methods: We studied paraffin
      embedded materials from 42 follicular adenomas (FA), 47 follicular variants of
      papillary carcinomas (FVPC) and 20 follicular carcinomas (FC) by the software
      ImageJ. Based on the nuclear morphometry and chromatin texture, the samples were
      classified as FA, FC or FVPC using the Classification and Regression Trees
      method. Results: We observed high diagnostic sensitivity and specificity rates
      (FVPC: 89.4% and 100%; FC: 95.0% and 92.1%; FA: 90.5 and 95.5%, respectively).
      When the tumors were compared by pairs (FC vs FA, FVPC vs FA), 100% of the cases
      were classified correctly. Conclusion: The computerized image analysis of nuclear
      features showed to be a useful diagnostic support tool for the histological
      differentiation between follicular adenomas, follicular variants of papillary
      carcinomas and follicular carcinomas.

PMID- 30299918
TI  - Dynamics of Architecturally Engineered All-Polymer Nanocomposites.
AB  - We present nanocomposite materials formed by using glassy star-shaped polymers as
      nanofillers and dispersing them in soft matrices. The resulting "architecturally
      engineered" polymer nanocomposites structurally reside between the linear
      homopolymer blends and the conventional polymer nanocomposites with inorganic
      fillers, inducing reinforcement, which can be as strong as that of solid
      nanoparticles, or softening depending on the compactness and concentration of the
      nanoparticles. Such behavior can be traced back to the dynamical features at the
      local segmental and the chain level, which we investigated using neutron
      scattering over a wide range of time and length scales in the glassy and melt
      states of the nanocomposites. The local and segmental dynamics as well as the
      degree of chain-chain entanglements are all modified by the star-shaped fillers.
      The presented approach to tuning the physical properties of all-polymer-based
      nanocomposites is readily adaptable to other polymer architectures with immediate
      applications in numerous areas including gas separation membranes, tissue
      engineering, drug delivery, and functional coatings.

PMID- 30299919
TI  - Thermal Percolation Threshold and Thermal Properties of Composites with High
      Loading of Graphene and Boron Nitride Fillers.
AB  - We investigated thermal properties of the epoxy-based composites with the high
      loading fraction-up to f ~ 45 vol %-of the randomly oriented electrically
      conductive graphene fillers and electrically insulating boron nitride fillers. It
      was found that both types of the composites revealed a distinctive thermal
      percolation threshold at the loading fraction fT > 20 vol %. The graphene loading
      required for achieving thermal percolation, fT, was substantially higher than the
      loading, fE, for electrical percolation. Graphene fillers outperformed boron
      nitride fillers in the thermal conductivity enhancement. It was established that
      thermal transport in composites with high filler loadings, f >= fT, is dominated
      by heat conduction via the network of percolating fillers. Unexpectedly, we
      determined that the thermal transport properties of the high loading composites
      were influenced strongly by the cross-plane thermal conductivity of the quasi-two
      dimensional fillers. The obtained results shed light on the debated mechanism of
      the thermal percolation, and facilitate the development of the next generation of
      the efficient thermal interface materials for electronic applications.

PMID- 30299921
TI  - Polyanthraquinone-Triazine-A Promising Anode Material for High-Energy Lithium-Ion
      Batteries.
AB  - A novel covalent organic framework polymer material that bears conjugated
      anthraquinone and triazine units in its skeleton has been prepared via a facile
      one-pot condensation reaction and employed as an anode material for Li-ion
      batteries. The conjugated units consist of C?N groups, C?O groups, and benzene
      groups, which enable a 17-electron redox reaction with Li per repeating unit and
      bring a theoretical specific capacity of 1450 mA h g-1. The polymer also shows a
      large specific surface area and a hierarchically porous structure to trigger
      interfacial Li storage and contribute to an additional capacity. The highly
      conductive conjugated polymer skeleton enables fast electron transport to
      facilitate the Li storage. In this way, the polymer electrode shows a large
      specific capacity and favorable cycling and rate performance, making it an
      appealing anode choice for the next-generation high-energy batteries.

PMID- 30299922
TI  - Localization of Protein Complex Bound Ligands by Surface-Induced Dissociation
      High-Resolution Mass Spectrometry.
AB  - Surface-induced dissociation (SID) is a powerful means of deciphering protein
      complex quaternary structures due to its capability of yielding dissociation
      products that reflect the native structures of protein complexes in solution.
      Here we explore the suitability of SID to locate the ligand binding sites in
      protein complexes. We studied C-reactive protein (CRP) pentamer, which contains a
      ligand binding site within each subunit, and cholera toxin B (CTB) pentamer,
      which contains a ligand binding site between each adjacent subunit. SID dissects
      ligand-bound CRP into subcomplexes with each subunit carrying predominantly one
      ligand. In contrast, SID of ligand-bound CTB results in the generation of
      subcomplexes with a ligand distribution reflective of two subunits contributing
      to each ligand binding site. SID thus has potential application in localizing
      sites of small ligand binding for multisubunit protein-ligand complexes.

PMID- 30299920
TI  - Manganese-Hydroxido Complexes Supported by a Urea/Phosphinic Amide Tripodal
      Ligand.
AB  - Hydrogen bonds (H-bonds) within the secondary coordination sphere are often
      invoked as essential noncovalent interactions that lead to productive chemistry
      in metalloproteins. Incorporating these types of effects within synthetic systems
      has proven a challenge in molecular design that often requires the use of rigid
      organic scaffolds to support H-bond donors or acceptors. We describe the
      preparation and characterization of a new hybrid tripodal ligand ([H2pout]3-)
      that contains two monodeprotonated urea groups and one phosphinic amide. The urea
      groups serve as H-bond donors, while the phosphinic amide group serves as a
      single H-bond acceptor. The [H2pout]3- ligand was utilized to stabilize a series
      of Mn-hydroxido complexes in which the oxidation state of the metal center ranges
      from 2+ to 4+. The molecular structure of the MnIII-OH complex demonstrates that
      three intramolecular H-bonds involving the hydroxido ligand are formed.
      Additional evidence for the formation of intramolecular H-bonds was provided by
      vibrational spectroscopy in which the energy of the O-H vibration supports its
      assignment as an H-bond donor. The stepwise oxidation of [MnIIH2pout(OH)]2- to
      its higher oxidized analogs was further substantiated by electrochemical
      measurements and results from electronic absorbance and electron paramagnetic
      resonance spectroscopies. Our findings illustrate the utility of controlling both
      the primary and secondary coordination spheres to achieve structurally similar Mn
      OH complexes with varying oxidation states.

PMID- 30299923
TI  - Transport Properties of Perfluorosulfonate Membranes Ion Exchanged with Cations.
AB  - In this work, the properties of univalent, that is, Li+, Na+, NH4+, and TEA+ form
      perfluorosulfonate (PFSA) membranes are studied and compared to the properties of
      H+ form materials. Properties of these polymer membranes including water uptake,
      density and conductivity, were investigated for membranes exposed to various
      water activity levels. The water uptake by the membranes decreased in the order
      H+ > Li+ > Na+ > NH4+ > TEA+, the same order as the hydration enthalpy (absolute
      values) of cations. Conductivity values did not strictly follow this order,
      indicating the importance of different factors besides the hydration level. The
      partial molar volume of water is derived from the density data as a function of
      water content for the various membrane forms. This provides further insight into
      the water, cation, and polymer interactions. Factors that contribute to the
      conductivity of these membranes include the size of cations, the electrostatic
      attraction between cations and sulfonate group, and the ion-dipole and hydrogen
      bonding interactions between cations and water. NH4+ transport is surprisingly
      high given the low water uptake in NH4+ form membranes. We attribute this to the
      ability of this ion to develop hydrogen bonded structures that helps to overcome
      electrostatic interactions with sulfonates. Pulsed-field gradient (PFG) nuclear
      magnetic resonance (NMR) was used to measure the diffusion coefficient of water
      in the membranes. FT-IR spectroscopy is employed to probe cation interactions
      with water and sulfonate sites in the polymer. Overall, the results reflect a
      competition between the strong electrostatic interaction between cation and
      sulfonate versus hydration and hydrogen bonding which vary with cation type.

PMID- 30299924
TI  - Visible Light Driven Organic Pollutants Degradation with Hydrothermally
      Carbonized Sewage Sludge and Oxalate Via Molecular Oxygen Activation.
AB  - Converting sewage sludge into functional environmental materials has become an
      attractive sewage sludge disposal route. In this study, we synthesize a sewage
      sludge-based material via a facile one-pot hydrothermal carbonization method and
      construct a visible light molecular oxygen activation system with hydrothermally
      carbonized sewage sludge (HTC-S) and oxalate to degrade various organic
      pollutants. It was found that iron species of HTC-S could chelate with oxalate to
      generate H2O2 via molecular oxygen activation under visible light, and also
      promote the H2O2 decomposition to produce *OH for the fast organic pollutants
      degradation. Taking sulfadimidine as the example, the apparent degradation rate
      of HTC-S/oxalate system was almost 5-20 times that of iron oxides/oxalate system.
      This outstanding degradation performance was attributed to the presence of iron
      containing clay minerals in HTC-S, as confirmed by X-ray diffraction measurements
      and Mossbauer spectrometry. In the oxalate solution, these iron-containing clay
      minerals could be excited more easily than common iron oxides under visible
      light, because the silicon species strongly interacted with iron species in HTC-S
      to form Fe-O-Si bond, which lowered the excitation energy of Fe-oxalate complex.
      This work provides an alternative sewage sludge conversion pathway and also sheds
      light on the environmental remediation applications of sewage sludge-based
      materials.

PMID- 30299925
TI  - Light-Tunable 1T-TaS2 Charge-Density-Wave Oscillators.
AB  - External stimuli-controlled phase transitions are essential for fundamental
      physics and design of functional devices. Charge density wave (CDW) is a
      metastable collective electronic phase featured by the periodic lattice
      distortion. Much attention has been attracted to study the external control of
      CDW phases. Although much work has been done in the electric-field-induced CDW
      transition, the study of the role of Joule heating in the phase transition is
      insufficient. Here, using the Raman spectroscopy, the electric-field-driven phase
      transition is in situ observed in the ultrathin 1T-TaS2. By quantitative
      evaluation of the Joule heating effect in the electric-field-induced CDW
      transition, it is shown that Joule heating plays a secondary role in the nearly
      commensurate (NC) to incommensurate (IC) CDW transition, while it dominants the
      IC-NC CDW transition, providing a better understanding of the electric field
      induced phase transition. More importantly, at room temperature, light
      illumination can modulate the CDW phase and thus tune the frequency of the
      ultrathin 1T-TaS2 oscillators. This light tunability of the CDW phase transition
      is promising for multifunctional device applications.

PMID- 30299926
TI  - High-Pressure Effect on the Optical Extinction of a Single Gold Nanoparticle.
AB  - When reducing the size of a material from bulk down to nanoscale, the enhanced
      surface-to-volume ratio and the presence of interfaces make the properties of
      nano-objects very sensitive not only to confinement effects but also to their
      local environment. In the optical domain, the latter dependence can be exploited
      to tune the plasmonic response of metal nanoparticles by controlling their
      surroundings, notably applying high pressures. To date, only a few optical
      absorption experiments have demonstrated this feasibility, on ensembles of metal
      nanoparticles in a diamond anvil cell. Here, we report a nontrivial combination
      between a spatial modulation spectroscopy microscope and an ultraflat diamond
      anvil cell, allowing us to quantitatively investigate the high-pressure optical
      extinction spectrum of an individual nano-object. A large tuning of the surface
      plasmon resonance of a gold nanobipyramid is experimentally demonstrated up to 10
      GPa, in quantitative agreement with finite-element simulations and an analytical
      model disentangling the impact of metal and local environment dielectric
      modifications. High-pressure optical characterizations of single nanoparticles
      allow for the accurate investigation and modeling of size, strain, and
      environment effects on physical properties of nano-objects and also enable fine
      tuned applications in nanocomposites, nanoelectromechanical systems, or
      nanosensing devices.

PMID- 30299927
TI  - LiCrS2 and LiMnS2 Cathodes with Extraordinary Mixed Electron-Ion Conductivities
      and Favorable Interfacial Compatibilities with Sulfide Electrolyte.
AB  - Sulfide-type solid-state electrolytes for all-solid-state lithium ion batteries
      are capturing more and more attention. However, the electronegativity difference
      between the oxygen and the sulfur element makes sulfide-type solid-state
      electrolytes chemically incompatible with the conventional LiCoO2 cathode. In
      this work, we proposed a series of chalcopyrite-structured sulfide-type materials
      and systematically assessed their performances as the cathode materials in all
      solid-state lithium ion batteries by first-principle calculations. All the five
      metallic LiMS2 (M = Cr, Mn, Fe, Co, and Ni) materials are superionic conductors
      with extremely small lithium ion migration barriers in the range from 43 to 99
      meV, much lower than most oxide- and even sulfide-type cathodes. Voltage and
      volume calculations indicate that only LiCrS2 and LiMnS2 cathodes are
      structurally stable during cycling with the stable voltage plateaus at ~3 V, much
      higher than that of the P3m1-LiTiS2 cathode. For the first time, we studied the
      interfacial lithium transport resistance from a new perspective of charge
      transfer and redistribution at the electrode/solid-state electrolyte interface.
      LiCrS2 and LiMnS2 cathodes exhibit favorable interfacial compatibilities with
      Li3PS4 electrolyte. Our investigations demonstrate that the metallic LiCrS2 and
      LiMnS2 superionic conductors would possess excellent rate capability, high energy
      density, good structural stability during cycling, and favorable interfacial
      compatibility with Li3PS4 electrolyte in all-solid-state lithium ion batteries.

PMID- 30299928
TI  - Toward Condensation-Resistant Omniphobic Surfaces.
AB  - Omniphobic surfaces based on reentrant surface structures repel all liquids,
      regardless of the surface material, without requiring low-surface-energy
      coatings. Although omniphobic surfaces have been designed and demonstrated, they
      can fail during condensation, a phenomenon ubiquitous in both nature and
      industrial applications. Specifically, as condensate nucleates within the
      reentrant geometry, omniphobicity is destroyed. Here, we show a nanostructured
      surface that can repel liquids even during condensation. This surface consists of
      isolated reentrant cavities with a pitch on the order of 100 nm to prevent
      droplets from nucleating and spreading within all structures. We developed a
      model to guide surface design and subsequently fabricated and tested these
      surfaces with various liquids. We demonstrated repellency to 10  degrees C below
      the dew point and showed durability over 3 weeks. This work provides important
      insights for achieving robust, omniphobic surfaces.

PMID- 30299930
TI  - TiO2@UiO-68-CIL: A Metal-Organic-Framework-Based Bifunctional Composite Catalyst
      for a One-Pot Sequential Asymmetric Morita-Baylis-Hillman Reaction.
AB  - A chiral ionic liquid (CIL) moiety of a l-pyrrolidin-2-ylimidazole-decorated
      homochiral UiO-68-type metal-organic framework, UiO-68-CIL (1), was successfully
      prepared by the combination of a new premodified chiral CIL ligand (H2L-CIL) and
      ZrCl4 via a solvothermal method. The TiO2-loaded TiO2@UiO-68-CIL (2) was prepared
      by impregnating 1 in a toluene solution of Ti(OPri)4 and sequential in situ
      hydrolysis. The obtained 2 can be a bifunctional asymmetric heterogeneous
      catalyst to successfully promote the one-pot Morita-Baylis-Hillman reaction
      starting from aromatic alcohols in a tandem way.

PMID- 30299929
TI  - Liquid Chromatography-Tandem Mass Spectrometry Approach for Determining
      Glycosidic Linkages.
AB  - The structural analysis of carbohydrates remains challenging mainly due to the
      lack of rapid analytical methods able to determine and quantitate glycosidic
      linkages between the diverse monosaccharides found in natural oligosaccharides
      and polysaccharides. In this research, we present the first liquid chromatography
      tandem mass spectrometry (LC-MS/MS)-based method for the rapid and simultaneous
      relative quantitation of glycosidic linkages for oligosaccharide and
      polysaccharide characterization. The method developed employs ultrahigh
      performance liquid chromatography coupled with triple quadrupole mass
      spectrometry (UHPLC/QqQ-MS) analysis performed in multiple reaction monitoring
      (MRM) mode. A library of 22 glycosidic linkages was built using commercial
      oligosaccharide standards. Permethylation and hydrolysis conditions along with LC
      MS/MS parameters were optimized resulting in a workflow requiring only 50 MUg of
      substrate for the analysis. Samples were homogenized, permethylated, hydrolyzed,
      and then derivatized with 1-phenyl-3-methyl-5-pyrazolone (PMP) prior to analysis
      by UHPLC/MRM-MS. Separation by C18 reversed-phase UHPLC along with the
      simultaneous monitoring of derivatized terminal, linear, bisecting, and
      trisecting monosaccharide linkages by mass spectrometry is achieved within a 15
      min run time. Reproducibility, efficacy, and robustness of the method was
      demonstrated with galactan ( Lupin) and polysaccharides within food such as whole
      carrots. The speed and specificity of the method enables its application toward
      the rapid glycosidic linkage analysis of oligosaccharides and polysaccharides.

PMID- 30299931
TI  - Effect of Interface Structure on the Mechanical Properties of Graphene Nanosheets
      Reinforced Copper Matrix Composites.
AB  - Currently, seldom studies have paid close attention to the impact of the defects
      and oxygen-containing functional groups on the surface of the graphene for
      composite applications. In this work, two typical graphene materials, namely
      graphene nanosheets synthesized by an in situ catalytic reaction and reduced
      graphene oxide (RGO), were adopted to fabricate reinforced copper matrix
      composites by spark plasma sintering. A harmful transitional interfacial layer
      made up of Cu/CuOx/amorphous carbon/RGO, resulted from interfacial reaction
      between Cu and RGO, were observed in the RGO/Cu composite. In contrast, the in
      situ synthesized graphene with fewer defect and lower oxygen level can realize
      clean graphene-Cu interface with Cu-O-C bonding and thus lead to much improved
      interface bonding and superior yield strength and tensile ductility. These
      results imply that the in situ synthesized graphene is more favorable for
      achievement of robust interfacial bonding for enhancing the mechanical properties
      of the graphene-Cu composites.

PMID- 30299932
TI  - Reply to Comment on METLIN: A Technology Platform for Identifying Knowns and
      Unknowns.

PMID- 30299933
TI  - Large-Area Preparation of Robust and Transparent Superomniphobic Polymer Films.
AB  - Transparent superamphiphobic surfaces that repel various liquids have many
      important applications, but there are critical challenges in their fabrication,
      such as expensive or complicated fabrication methods, contradictions between the
      rough surface for superamphiphobicity and smooth surface for transparency, large
      area fabrication, etc. Herein, we report a simple and effective strategy for
      large-scale fabrication of robust, transparent, and superomniphobic polymer films
      by combined unidirectional rubbing and heating-assisted assembly technology. The
      obtained polymer films display two kinds of special structures of monolayer
      ordered re-entrant geometries with either hexagonally triangular protrusions or
      with hexagonally rectangular micropillars, depending upon the sphere diameters of
      silica templates, and demonstrate excellent repellence to water and low-surface
      tension liquids, as well as high transparency.

PMID- 30299934
TI  - Design for Brighter Photon Upconversion Emissions via Energy Level Overlap of
      Lanthanide Ions.
AB  - The perfect energy level overlap of 2H11/2, 4S3/2, and 4F9/2 in Er3+ ions with
      those of 5F3, 5F4/5S2, and 5F5 in adjacently codoped Ho3+ ions allows efficient
      interenergy transfer. Therefore, in addition to routine activators, Er3+ or Ho3+
      can further act as sensitizers to transfer the upconverted energy to nearby Ho3+
      or Er3+, resulting in enhanced upconversion luminescence due to the emission
      overlap. Proper codoping of Er3+/Ho3+ or Ho3+/Er3+ obviously elevates the maximum
      doping concentration (thus producing additional upconverted photons) to a level
      higher than that causing luminescence quenching and significantly enhances
      upconversion emissions compared with those of singly Er3+ or Ho3+-doped host
      materials. Indeed, the so-far strongest red upconversion emission under 1532 nm
      excitation was obtained in LiYF4:Er/Ho@LiYF4 nanoparticles and Ho3+-sensitized
      Er3+ upconversion emissions excited by 1150 nm laser was simultaneously
      discovered. With great enhancement compared with that of singly Ho3+ doped
      counterparts, this work demonstrates the generality and rationality of our design
      strategy.

PMID- 30299935
TI  - Facile Synthesis of Na-Doped MnO2 Nanosheets on Carbon Nanotube Fibers for
      Ultrahigh-Energy-Density All-Solid-State Wearable Asymmetric Supercapacitors.
AB  - Flexible fiber-shaped supercapacitors hold promising potential in the area of
      portable and wearable electronics. Unfortunately, their general application is
      hindered by the restricted energy densities due to low operating voltage and
      small specific surface area. Herein, an all-solid-state fiber-shaped asymmetric
      supercapacitor (FASC) possessing ultrahigh energy density is reported, in which
      the positive electrode was designed as Na-doped MnO2 nanosheets on carbon
      nanotube fibers (CNTFs) and the negative electrode as MoS2 nanosheet-coated
      CNTFs. Owing to the excellent properties of the designed electrodes, our FASCs
      exhibit a large operating potential window (0-2.2 V), a remarkable specific
      capacitance (265.4 mF/cm2), as well as an ultrahigh energy density (178.4
      MUWh/cm2). Moreover, the devices are of outstanding mechanical flexibility.

PMID- 30299936
TI  - Fe(VI)-Mediated Single-Electron Coupling Processes for the Removal of
      Chlorophene: A Combined Experimental and Computational Study.
AB  - Potassium ferrate [Fe(VI)] is a promising oxidant widely used in water treatment
      for the elimination of organic pollutants. In this work, the reaction kinetics,
      products, and mechanisms of the antimicrobial agent chlorophene (CP) undergoing
      Fe(VI) oxidation in aqueous solutions were investigated. CP is very readily
      degraded by Fe(VI), with the apparent second-order rate constant, k, being 423.2
      M-1 s-1 at pH 8.0. A total of 22 oxidation products were identified using liquid
      chromatography-quadrupole time-of-flight-mass spectrometry , and their structures
      were further elucidated using tandem mass spectrometry. According to the
      extracted peak areas in mass spectra, the main reaction products were the
      coupling products (dimers, trimers, and tetramers) that formed via single
      electron coupling. Theoretical calculations demonstrated that hydrogen
      abstraction should easily occur at the hydroxyl group to produce reactive CP.
      radicals for subsequent polymerization. Cleavage of the C-C bridge bond,
      electrophilic substitution, hydroxylation, ring opening, and decarboxylation were
      also observed during the Fe(VI) oxidation process. In addition, the degradation
      of CP by Fe(VI) was also effective in real waters, which provides a basis for
      potential applications.

PMID- 30299937
TI  - Comment on METLIN: A Technology Platform for Identifying Knowns and Unknowns.

PMID- 30299938
TI  - Urokinase-Conjugated Magnetite Nanoparticles as a Promising Drug Delivery System
      for Targeted Thrombolysis: Synthesis and Preclinical Evaluation.
AB  - Mortality and disabilities as outcomes of cardiovascular diseases are primarily
      related to blood clotting. Optimization of thrombolytic drugs is aimed at the
      prevention of side effects (in particular, bleeding) associated with a disbalance
      between coagulation and anticoagulation caused by systemically administered
      agents. Minimally invasive and efficient approaches to deliver the thrombolytic
      agent to the site of clot formation are needed. Herein, we report a novel
      nanocomposite prepared by heparin-mediated cross-linking of urokinase with
      magnetite nanoparticles (MNPs@uPA). We showed that heparin within the composition
      evoked no inhibitory effects on urokinase activity. Importantly, the magneto
      control further increased the thrombolytic efficacy of the composition. Using our
      nanocomposition, we demonstrated efficient lysis of experimental clots in vitro
      and in animal vessels followed by complete restoration of blood flow. No
      sustained toxicity or hemorrhagic complications were registered in rats and
      rabbits after single bolus i.v. injection of therapeutic doses of MNPs@uPA. We
      conclude that MNPs@uPA is a prototype of easy-to-prepare, inexpensive,
      biocompatible, and noninvasive thrombolytic nanomedicines potentially useful in
      the treatment of blood clotting.

PMID- 30299939
TI  - From Transition Metals to Lanthanides to Actinides: Metal-Mediated Tuning of
      Electronic Properties of Isostructural Metal-Organic Frameworks.
AB  - Isostructural metal-organic frameworks (MOFs) have been prepared from a variety
      of metal-oxide clusters, including transition metals, lanthanides, and actinides.
      Experimental and calculated shifts in O-H stretching frequencies for hydroxyl
      groups associated with the metal-oxide nodes reveal varying electronic properties
      for these units, thereby offering opportunities to tune support effects for other
      materials deposited onto these nodes.

PMID- 30299940
TI  - beta-Cyclodextrin-Modified Magnetic Nanoparticles Immobilized on Sepharose
      Surface Provide an Effective Matrix for Protein Refolding.
AB  - In this article, we propose an impressive and facile strategy to improve protein
      refolding using solid phase artificial molecular chaperones consisting of the
      surface-functionalized magnetic nanoparticles. Specifically, monotosyl-beta
      cyclodextrin connected to the surface of 3-aminopropyltriethoxysilane (APES)
      modified magnetic nanoparticles is immobilized on the sepharose surface to
      promote interaction with exposed hydrophobic surfaces of partially folded
      (intermediates) and unfolded states of proteins. Their efficiencies were
      investigated by circular dichroism spectroscopy and photoluminescence
      spectroscopy of the protein. Although the mechanism of this method is based on
      principles of hydrophobic chromatography, this system is not only purging the
      native protein from inactive inclusion bodies but also improving the protein
      refolding process. We chose beta-cyclodextrin (beta-CD) considering multiple
      reports in the literature about its efficiency in protein refolding and its
      biocompatibility. To increase the surface area/volume ratio of the sepharose
      surface by nanoparticles, more beta-CD molecules are connected to the sepharose
      surface to make a better interaction with proteins. We suppose that proteins are
      isolated in the nanospace created by bound cyclodextrins on the resin surface so
      intermolecular interactions are reduced. The architecture of nanoparticles was
      characterized by Fourier transform infrared spectra, X-ray diffraction, scanning
      electron microscopy images, energy dispersive X-ray spectroscopy, nuclear
      magnetic resonance (1H NMR and 13C NMR), and dynamic light scattering.

PMID- 30299941
TI  - Surface Hopping within an Exciton Picture. An Electrostatic Embedding Scheme.
AB  - We report the development and the implementation of an exciton approach that
      allows ab initio nonadiabatic dynamics simulations of electronic excitation
      energy transfer in multichromophoric systems. For the dynamics, a trajectory
      based strategy is used within the surface hopping formulation. The approach
      features a consistent hybrid formulation that allows the construction of
      potential energy surfaces and gradients by combining quantum mechanics and
      molecular mechanics within an electrostatic embedding scheme. As an application,
      the study of a molecular dyad consisting of a covalently bound BODIPY moiety and
      a tetrathiophene group is presented using time-dependent density functional
      theory (TDDFT). The results obtained with the exciton model are compared to
      previously performed full TDDFT dynamics of the same system. Our results show
      excellent agreement with the full TDDFT results, indicating that the couplings
      that lead to excitation energy transfer (EET) are dominated by Coulomb
      interaction terms and that charge-transfer states are not necessary to properly
      describe the nonadiabatic dynamics of the system. The exciton model also reveals
      ultrafast coherent oscillations of the excitation between the two units in the
      dyad, which occur during the first 50 fs.

PMID- 30299942
TI  - Correction to "Enantioselective Synthesis of alpha-Amidoboronates Catalyzed by
      Planar-Chiral NHC-Cu(I) Complexes".

PMID- 30299943
TI  - Investigation of Physiological Properties of Transglycosylated Stevia with
      Cationic Surfactant and Its Application To Enhance the Solubility of Rebamipide.
AB  - The poor water solubility of rebamipide was enhanced by the mixed micelles of
      transglycosylated stevia (Stevia-G) and trimethylammonium chloride with varying
      carbon chain length (C nTAC, n = 14, 16, and 18). Fluorometry, isothermal
      titration calorimetry (ITC) and dynamic light scattering techniques examined the
      aggregation properties of Stevia-G and C nTAC. Synergism was found between Stevia
      G and C nTAC using the approaches of Clint and Rubingh. The negative interaction
      parameter (average betam = -4.17, -5.47, and -7.07) and excess free energy
      (average DeltaG degrees ex = -2.47, -3.06, and -3.88 kJ mol-1) increased with
      increasing chain length of C nTAC. The negative B1 values by the Maeda approach
      suggested that chain-chain interactions contribute to the formation of a mixed
      micelle. The solubilization of rebamipide in the mixed micelle was evaluated in
      the term of the molar solubilization ratio (MSR) and partition coefficient ( Km).
      The Km from the Stevia-G/C16TAC system was highest at a low mole fraction of C
      nTAC (0.2-0.6). In conclusion, the solubilization of rebamipide was more
      favorable between Stevia-G and C16TAC, although the stability of the mixed
      micelle was enhanced by an increase in hydrophobicity of the longer chain lengths
      used in C nTAC.

PMID- 30299944
TI  - Crystal Structure Determination of Ubiquitin by Fusion to a Protein That Forms a
      Highly Porous Crystal Lattice.
AB  - The protein crystallization process requires screening of a large number of
      conditions using a large quantity of high-purity protein, which makes crystal
      structure analysis difficult. Thus, the development of easy and versatile protein
      crystallization techniques is both extremely desirable and highly challenging.
      Here I demonstrate the crystallization and structure determination of ubiquitin
      by genetic fusion to the highly porous honeycomb lattice of R1EN. I successfully
      crystallized and collected X-ray data from three R1EN-ubiquitin constructs with
      various linker lengths under the same conditions as the original R1EN. The
      crystals diffracted to 1.7-2.4 A resolution, and the ubiquitin structures were
      determined with results almost identical to the previously published structure.
      Moreover, the ubiquitin structure could be solved by molecular replacement using
      R1EN alone. This method may reduce the effort required for crystallization
      screening and is applicable to de novo protein structure determination.

PMID- 30299945
TI  - Semiclassical Treatment of High-Lying Electronic States of H2.
AB  - We report quantum-mechanical and semiclassical WKB calculations for energies and
      wave functions of high-lying 2Sigma states of H2+ in atomic units. The high-lying
      states we present lie in an unexplored regime, corresponding asymptotically to H
      ( n <= 146) plus a proton, with R <= 120 000 a0. We compare quantum-mechanical
      energies, spectroscopic constants, dipole matrix elements, and phases with
      semiclassical results and demonstrate a high level of agreement. Our quantum
      mechanical phases were determined by using Milne's phase-amplitude procedure. We
      compare our semiclassical energies for low-lying states with those of other
      researchers.

PMID- 30299946
TI  - Development of Multifunctional Avermectin Poly(succinimide) Nanoparticles to
      Improve Bioactivity and Transportation in Rice.
AB  - Avermectin (AVM) as a nonsystemic pesticide possesses a low effective utilization
      rate. Studies of the multifunctional pesticide delivery system for improving
      biological activity are developing prosperously. In this study, multifunctional
      avermectin/polysuccinimide with glycine methyl ester nanoparticles (AVM-PGA) were
      prepared by the self-assembly process. The AVM loading capacity was up to 23.7%.
      After 24 h of UV irradiation, there was still about 70% of AVM remaining in PGA42
      nanocarriers, as opposed to less than 5% of the free-form AVM. The rising ambient
      pH promoted the release of AVM using an in vitro releasing test, revealing a
      favorable pH-responsively controlled-release property. The mortality rate of
      Plutella xylostella with 2.5 MUg/mL of AVM content of AVM-PGA42 was 96.3% after
      48 h, while that of free AVM was only 51.5%. In addition, the AVM could be
      detected in stems and all leaves treated with AVM-PGA42 nanoparticles, whereas
      rare AVM was detected only in treated leaves for the free-form AVM, which
      achieved the transportation of nanocarriers carrying AVM in rice for the first
      time. Furthermore, the PGA nanoparticles performed a good growth promoting effect
      on rice. These results show that the AVM-PGA42 nanopesticides have a great
      potential application prospect to control the pest and improve the drug
      utilization efficiency on agriculture.

PMID- 30299947
TI  - Sr2FeIrO4: Square-Planar Ir(II) in an Extended Oxide.
AB  - Topochemical reduction of the double-perovskite oxide Sr2FeIrO6 under dilute
      hydrogen leads to the formation of Sr2FeIrO4. This phase consists of ordered
      infinite sheets of apex-linked Fe2+O4 and Ir2+O4 squares stacked with Sr2+
      cations and is the first report of Ir2+ in an extended oxide phase. Plane-wave
      density functional theory calculations indicate high-spin Fe2+ (d6, S = 2) and
      low-spin Ir2+ (d7, S = 1/2) configurations for the metals and confirm that both
      ions have a doubly occupied d z2 orbital, a configuration that is emerging as a
      consistent feature of all layered oxide phases of this type. The stability and
      double occupation of d z2 in the Ir2+ ions invites a somewhat unexpected analogy
      to the extensively studied Ir4+ ion as both ions share a common near-degenerate
      (d xy/ xz/ yz)5 valence configuration. On cooling below 115 K, Sr2FeIrO4 enters a
      magnetically ordered state in which the Ir and Fe sublattices adopt type II
      antiferromagnetically coupled networks which interpenetrate each other, leading
      to frustration in the nearest-neighbor Fe-O-Ir couplings, half of which are
      ferromagnetic and half antiferromagnetic. The spin frustration drives a symmetry
      lowering structural distortion in which the four equivalent Ir-O and Fe-O
      distances of the tetragonal I4/ mmm lattice split into two mutually trans pairs
      in a lattice with monoclinic I112/ m symmetry. This strong magneto-lattice
      coupling arises from the novel local electronic configurations of the Fe2+ and
      Ir2+ cations and their cation-ordered arrangement in a distorted perovskite
      lattice.

PMID- 30299948
TI  - Accuracy of Coupled Cluster Excited State Potential Energy Surfaces.
AB  - The validation of the quality of the description of excited electronic states is
      of special importance in quantum chemistry as the general reliability of ab
      initio methods shows a much larger variation for these states than for the ground
      state. In this study, we investigate the quality of excited state energy
      gradients and potential energy surfaces on selected systems, as provided by the
      single reference coupled cluster variants CC2, CCSD, CCSD(T)(a)*, and CC3.
      Gradients and surface plots that follow the Franck-Condon forces are compared to
      the respective CCSDT reference values, thereby establishing a useful strategy for
      judging each variant's accuracy. The results reveal serious flaws of lower order
      methods - in particular, CC2 - in several situations where they otherwise give
      accurate vertical excitation energies, as well as excellent accuracy and
      consistency of the recently proposed CCSD(T)(a)* method.

PMID- 30299950
TI  - Lessons from the Spin-Polarization/Spin-Contamination Dilemma of Transition-Metal
      Hyperfine Couplings for the Construction of Exchange-Correlation Functionals.
AB  - Hyperfine couplings (HFCs) of open-shell transition-metal centers are known to
      often depend crucially on core-shell spin polarization (CSSP). The latter is
      typically underestimated by semilocal density functionals, while admixture of
      exact exchange (EXX) in (global) hybrid functionals enhances CSSP. Unfortunately,
      a metal-ligand antibonding character of one or more of the singly occupied
      molecular orbitals of the complex will cause substantial valence-shell spin
      polarization (VSSP), which for global hybrids with higher EXX admixtures may lead
      to substantial spin contamination, thereby deteriorating the overall electronic
      structure and the dipolar couplings. In view of this known dilemma, we use a
      subset of 3d complexes from an earlier study (M. Munzarova, M. Kaupp J. Phys.
      Chem. A 1999, 103, 9966-9983) to examine systematically a wide range of exchange
      correlation functionals for metal HFCs, including highly parametrized (meta
      )GGAs, global, and range-separated hybrid functionals not yet available in
      earlier studies, as well as for the first time local hybrids with real-space
      position-dependent EXX admixture. Both CSSP and VSSP have been carefully analyzed
      in terms of their orbital contributions, both for cases dominated only by CSSP
      and for systems influenced crucially by VSSP and spin contamination. While some
      more parametrized meta-GGA functionals (tau-HCTH, VSXC, partially M06-L) provide
      surprisingly realistic CSSP, some others (MN12-L, MN15-L) and some global hybrids
      (M05, M06, partly MN15) exhibit dramatic shortcomings in describing the CSSP
      contributions. Local hybrid functionals provide a promising way of enhancing CSSP
      by high EXX admixture in the core region while avoiding excessive VSSP and thus
      spin contamination. These analyses provide important insights that may help to
      construct improved functionals for HFCs and related properties (e.g., contact NMR
      shifts).

PMID- 30299949
TI  - Electronically Excited Solute Described by RISM Approach Coupled with
      Multireference Perturbation Theory: Vertical Excitation Energies of Bioimaging
      Probes.
AB  - For theoretically studying molecules with fluorescence in the near-infrared
      region, high-accuracy determination of state energy level is required for
      meaningful analyses since the spectra of interest are of very narrow energy
      range. In particular, these molecules are in many cases handled in solution;
      therefore, consideration of the solvation effect is essential upon calculation
      together with the electronic structure of the excited state. Earlier studies
      showed that they cannot be described with conventional methods such as PCM-TD
      DFT, yielding results far from experimental data. Here, we have developed a new
      method by combining a solvation theory based on statistical mechanics (RISM) and
      a multireference perturbation theory (CASPT2) with the extension of the density
      matrix renormalization group reference states for calculating the photochemical
      properties of near-infrared molecules and have obtained higher-accuracy
      prediction.

PMID- 30299951
TI  - Linking Molybdenum-Sulfur Clusters for Electrocatalytic Hydrogen Evolution.
AB  - Controlling the spatial arrangement of molecular catalysts on electrodes is
      critical to developing an optimal electrocatalyst. Mo-S clusters have shown great
      promise in catalyzing hydrogen evolution for the generation of carbon-free fuel
      from water. Here we report a synthetic approach to organize these molecular
      clusters into ordered dimers, cages, and chains through the use of organic
      linkers, as solved by single-crystal X-ray diffraction. We find that the linkage
      through the coordination bond between thiolate and Mo3S7 leads to (1) a 40-fold
      enhancement in turnover frequency compared with the unlinked cluster and (2) the
      periodic arrangement of clusters on the electrode with control over their
      distance, orientation, and density, thus enabling hydrogen evolution at high
      catalyst loading. The materials developed here require an overpotential of only
      89 mV to achieve a current density of 10 mA cm-2, outperforming other Mo-S
      catalysts (both molecular and solid-state).

PMID- 30299952
TI  - Insight into the Solvation Structure of Tetraglyme-Based Electrolytes via First
      Principles Molecular Dynamics Simulation.
AB  - Glyme-lithium salt equimolar mixtures, as solvate ionic liquid electrolytes for
      rechargeable lithium secondary batteries, are of great interest, due to the
      desirable properties such as high oxidative stability, low vapor pressure, and
      nonflammability. However, the fundamental understanding of the solvation shell
      structure in glyme electrolytes has not been clearly established. Herein, we
      employ first-principles molecular dynamics (FPMD) simulation to study the lithium
      bis(trifluoromethylsulfonyl)-amide (LiTFSA) and tetraglyme (G4) electrolyte
      system. For the case of equimolar ratio, a positive correlation between the total
      coordination number of Li+ ions and the phase stability is clearly established.
      At the ground state of equimolar LiTFSA-G4 electrolyte, most of the Li+ ions are
      coordinated to four O atoms of a curled G4 molecule and one O atom of a TFSA-
      anion, equivalent to the second most stable contact ion pair in gas-phase cluster
      calculations. By contrast, Li+ ions prefer to be coordinated by two G4 molecules
      and not in direct contact with TFSA- anions at a low concentration of Li salt.
      The significantly increased probability of pairing between the Li-G4 complexes
      and TFSA- anions at the equimolar ratio could be highly relevant to its ionic
      liquid-like properties.

PMID- 30299953
TI  - The Nonlocal Kernel in van der Waals Density Functionals as an Additive
      Correction: An Extensive Analysis with Special Emphasis on the B97M-V and
      omegaB97M-V Approaches.
AB  - The development of van der Waals density functional approximations (vdW-DFAs) has
      gained considerable interest over the past decade. While in a strictest sense,
      energy calculations with vdW-DFAs should be carried out fully self-consistently,
      we demonstrate conclusively for a total of 11 methods that such a strategy only
      increases the computational time effort without having any significant effect on
      energetic properties, electron densities, or orbital-energy differences. The
      strategy to apply a nonlocal vdW-DFA kernel as an additive correction to a fully
      converged conventional DFA result is therefore justified and more efficient. As
      part of our study, we utilize the extensive GMTKN55 database for general main
      group thermochemistry, kinetics, and noncovalent interactions [ Phys. Chem. Chem.
      Phys. 2017, 19, 32184], which allows us to analyze the very promising B97M-V [ J.
      Chem. Phys. 2015, 142, 074111] and omegaB97M-V [ J. Chem. Phys. 2016, 144,
      214110] DFAs. We also present new DFT-D3(BJ) based counterparts of these two
      methods and of omegaB97X-V [ J. Chem. Theory Comput 2013, 9, 263], which are
      faster variants with similar accuracy. Our study concludes with updated
      recommendations for the general method user, based on our current overview of 325
      dispersion-corrected and -uncorrected DFA variants analyzed for GMTKN55. vdW-DFAs
      are the best representatives of the three highest rungs of Jacob's Ladder,
      namely, B97M-V, omegaB97M-V, and DSD-PBEP86-NL.

PMID- 30299954
TI  - Achieving Fast and Efficient K+ Intercalation on Ultrathin Graphene Electrodes
      Modified by a Li+ Based Solid-Electrolyte Interphase.
AB  - Advancing beyond Li-ion batteries requires translating the beneficial
      characteristics of Li+ electrodes to attractive, yet incipient, candidates such
      as those based on K+ intercalation. Here, we use ultrathin few-layer graphene
      (FLG) electrodes as a model interface to show a dramatic enhancement of K+
      intercalation performance through a simple conditioning of the solid-electrolyte
      interphase (SEI) in a Li+ containing electrolyte. Unlike the substantial plating
      occurring in K+ containing electrolytes, we found that a Li+ based SEI enabled
      efficient K+ intercalation with discrete staging-type phase transitions observed
      via cyclic voltammetry at scan rates up to 100 mVs-1 and confirmed as ion
      intercalation processes through in situ Raman spectroscopy. The resulting
      interface yielded fast charge-discharge rates up to ~360C (1C is fully discharge
      in 1 h) and remarkable long-term cycling stability at 10C for 1000 cycles. This
      SEI promoted the transport of K+ as verified via mass spectrometric depth
      profiling. This work introduces a convenient strategy for improving the
      performance of ion intercalation electrodes toward a practical K-ion battery and
      FLG electrodes as a powerful analytical platform for evaluating fundamental
      aspects of ion intercalation.

PMID- 30299955
TI  - Major G-Quadruplex Form of HIV-1 LTR Reveals a (3 + 1) Folding Topology
      Containing a Stem-Loop.
AB  - Nucleic acids can form noncanonical four-stranded structures called G
      quadruplexes. G-quadruplex-forming sequences are found in several genomes
      including human and viruses. Previous studies showed that the G-rich sequence
      located in the U3 promoter region of the HIV-1 long terminal repeat (LTR) folds
      into a set of dynamically interchangeable G-quadruplex structures. G-quadruplexes
      formed in the LTR could act as silencer elements to regulate viral transcription.
      Stabilization of LTR G-quadruplexes by G-quadruplex-specific ligands resulted in
      decreased viral production, suggesting the possibility of targeting viral G
      quadruplex structures for antiviral purposes. Among all the G-quadruplexes formed
      in the LTR sequence, LTR-III was shown to be the major G-quadruplex conformation
      in vitro. Here we report the NMR structure of LTR-III in K+ solution, revealing
      the formation of a unique quadruplex-duplex hybrid consisting of a three-layer (3
      + 1) G-quadruplex scaffold, a 12-nt diagonal loop containing a conserved duplex
      stem, a 3-nt lateral loop, a 1-nt propeller loop, and a V-shaped loop. Our
      structure showed several distinct features including a quadruplex-duplex
      junction, representing an attractive motif for drug targeting. The structure
      solved in this study may be used as a promising target to selectively impair the
      viral cycle.

PMID- 30299957
TI  - Identification and Enantiodivergent Synthesis of (5 Z,9 S)-Tetradec-5-en-9-olide,
      a Queen-Specific Volatile of the Termite Silvestritermes minutus.
AB  - The queens of social insects differ from sterile colony members in many aspects
      of their physiology. Besides adaptations linked with their specialization for
      reproduction and extended lifespan, the queens also invest in the maintenance of
      their reproductive dominance by producing exocrine chemicals signaling their
      presence to the nestmates. The knowledge of the chemistry of queen-specific cues
      in termites is scarce. In addition to the contact recognition based on cuticular
      hydrocarbons, long-range signals mediated by volatiles are expected to
      participate in queen signaling, especially in populous colonies of higher
      termites (Termitidae). In queens of the higher termite Silvestritermes minutus
      (Syntermitinae), we have detected a previously undescribed volatile. It is
      present in important quantities on the body surface and in the headspace,
      ovaries, and body cavity. MS and GC-FTIR data analyses led us to propose the
      structure of the compound to be a macrolide 10-pentyl-3,4,5,8,9,10-hexahydro-2 H
      oxecin-2-one. We performed enantiodivergent syntheses of two possible enantiomers
      starting from enantiopure ( S)-glycidyl tosylate. The synthetic sequence involved
      macrolide-closing metathesis quenched with a ruthenium scavenging agent. The
      absolute and relative configuration of the compound was assigned to be (5 Z,9 S)
      tetradec-5-en-9-olide. Identification and preparation of the compound allow for
      investigation of its biological significance.

PMID- 30299958
TI  - Water-Soluble Leaving Group Enables Hydrophobic Functionalization of RNA.
AB  - Attachment of hydrophobic groups to RNA is challenging because of their poor
      aqueous solubility. One-step acylation of RNA 2'-OH groups in water using a water
      soluble imidazole leaving group is described. The effect of the hydrophobic
      groups on hybridization is reported. Furthermore, propargyl-functionalized RNA is
      shown to be readily labeled with a fluorophore. Lastly, heptyl-functionalized RNA
      is found to exhibit the unusual property of solubility in organic solvents.

PMID- 30299956
TI  - Zinc Oxide Nanoparticle as a Novel Class of Antifungal Agents: Current Advances
      and Future Perspectives.
AB  - Certain types of nanoparticles, especially zinc oxide nanoparticles (ZnONPs), are
      widely reported to be capable of the inhibition of harmful bacteria, yeasts, and
      filamentous fungi. The unique physicochemical and biological properties of ZnONPs
      also make them attractive to the food industry for use as a promising antifungal
      agent. This Review thoroughly introduces the preparation methods and antifungal
      properties of ZnONPs and analyzes their possible antifungal mechanisms. The
      applicability of ZnONPs in food packaging and nutritional supplements and as an
      antimicrobial additive is also documented. Moreover, evaluations for biological
      safety of ZnONPs are objectively reviewed in this paper. The discussions
      addressed in this Review not only have theoretical significance but also are
      conducive to the development of food safety, nutrition, and human health. The
      summarized knowledge and future perspectives outlined here are expected to
      promote and guide new research toward developing and optimizing the application
      of ZnONPs as a novel class of antifungal agents to help improve food quality as
      well as food safety in the near future.

PMID- 30299959
TI  - Competing Intramolecular Hydrogen Bond Strengths and Intermolecular Interactions
      in the 4-Aminobutanol-Water Complex.
AB  - We seek to determine the effect of competing intermolecular hydrogen bonds from
      water on the preferred conformation of 4-aminobutanol (4AB) monomers stabilized
      by intramolecular hydrogen bonds. Toward this end, the rotational spectrum of the
      4-aminobutanol-H2O complex was recorded using Fourier transform microwave
      spectroscopy and fit to the rotational, quadrupole coupling, and centrifugal
      distortion constants of the Watson S-reduction Hamiltonian. The experimental
      results are consistent with a 4AB-water complex that preserves the intramolecular
      hydrogen bond within the 4AB monomer and forms a single intermolecular bond with
      water acting as a donor. The experimental monomer structure agrees well with the
      lowest energy conformation calculated at the MP2/6-311++G(d,p) level of theory.
      Upon complex formation and the introduction of competing intermolecular bonds
      from water, only small changes in the OH...N intramolecular hydrogen bond and
      backbone torsional angles of the 4-aminobutanol monomer are observed. Similar
      small changes were observed for the shorter chain 3-aminopropanol amino alcohol
      monomer when complexed with water, in contrast to the 2-aminoethanol-H2O complex.
      In the latter, a large change in the backbone torsional angle and a breaking of
      the intramolecular hydrogen bond were observed. Thus, extending the methylene
      chain results in an increase in the strength of the intramolecular hydrogen bond
      in unbranched amino alcohols.

PMID- 30299960
TI  - Zinc-Induced Conformational Transitions in Human Islet Amyloid Polypeptide and
      Their Role in the Inhibition of Amyloidosis.
AB  - Type-2 diabetes mellitus (T2DM) is a disease hallmarked by improper homeostasis
      within the islets of Langerhans of the pancreas. The most critical species
      affected is insulin, which is produced by the beta-cells of the islets, but there
      are a number of other species copackaged and cosecreted within the insulin
      granules. This includes zinc, which exists in high (millimolar) concentrations
      within the beta-cells, and islet amyloid polypeptide (IAPP), which is an amyloid
      peptide thought to induce beta-cell apoptosis through self-association into toxic
      amyloid oligomers. Zinc is essential in the packaging of crystalline insulin
      within the vesicles but it can also bind and interact with IAPP. This implies a
      complex relationship between all three species and diabetes, particularly in the
      structure and function of toxic IAPP aggregates. Atypical (low or high)
      concentrations of zinc generally appear to correlate with increased hIAPP
      aggregation, whereas physiological zinc concentrations have an inhibitory effect.
      To better understand how zinc ions alter the monomer and oligomer structure of
      hIAPP in vitro, we employ a combination of ion mobility mass spectrometry and
      atomic force microscopy. We observe an increase in the extended beta-hairpin
      conformation of hIAPP when it is bound to zinc. With sufficiently low
      concentrations of zinc this could result in an association site for zinc-free
      hIAPP, promoting amyloid aggregation. At high zinc concentrations, we see the
      appearance of a secondary zinc association site whose coordination could account
      for the loss of inhibition at high zinc concentrations. Generally, it appears
      that zinc preferentially stabilizes the beta-hairpin conformation of hIAPP and
      the population of zinc-bound hIAPP in solution determines what effect this has on
      amyloid aggregation.

PMID- 30299961
TI  - Characterization of Laser Gold Nanowarming: A Platform for Millimeter-Scale
      Cryopreservation.
AB  - Preventing ice formation during cryopreservation by vitrification has led to the
      successful storage and banking of numerous cellular- and tissue-based
      biomaterials. In their breakthrough work, Peter Mazur's group achieved over 90%
      survival by using a laser warming technique for 100 MUm mice oocytes that were
      cooled in 0.1 MUL droplets with 2.3 M CPA and extracellularly loaded India ink
      (laser absorber). Laser warming can provide rapid and uniform warming rates to
      "outrun" damaging ice crystal growth. Here we generalize Mazur's technique for
      microliter-sized droplets using laser nanowarming to rewarm millimeter-scale
      biomaterials when loaded extracellularly and/or intracellularly with
      biocompatible 1064 nm resonant gold nanoparticles. First, we show that droplets
      containing low-concentration cryoprotectants (such as 2 M propylene glycol +/- 1
      M trehalose) can be rapidly cooled at rates up to 90 000  degrees C/min by
      plunging into liquid nitrogen to achieve either a visually transparent state
      (i.e., vitrified) or a cloudy with ice (i.e., nonvitrified) state. Both modeling
      and experiments were then used to characterize the laser nanowarming process for
      different laser energy (2-6 J), pulse length (1-20 ms), droplet volume (0.2-1.8
      MUL), cryoprotectant (2-3 M), and gold concentration (0.77 * 1017-4.8 * 1017
      nps/m3) values to assess physical and biological success. Physical success was
      achieved by finding conditions that minimize cloudiness and white spots within
      the droplets during cooling and warming as signs of damaging ice formation and
      ice crystallization, respectively. Biological success was achieved using human
      dermal fibroblasts to find conditions that achieve >=90% cell viability
      normalized to controls postwarming. Thus, physical and biological success can be
      achieved using this platform cryopreservation approach of rapid cooling and laser
      gold nanowarming in millimeter-scale systems.

PMID- 30299962
TI  - Nanoscale Topographical Fluctuations: A Key Factor for Evaporative Colloidal Self
      Assembly.
AB  - This work investigates the role of surface parameters such as the nanoscale
      roughness, topography, and skewness of smooth and rough Si surfaces in the shape
      of patterns left by evaporating colloidal droplets of spherical polystyrene
      particles. The droplet contact angle, colloidal deposition pattern, crack
      density, and rim growth velocities are experimentally evaluated for varying
      roughness. The contact angle and rim growth rate are found to be more for rough
      surfaces in comparison to smooth ones. Roughness also helps in reducing stress in
      the drying droplets, thereby impeding the process of crack formation as
      exemplified by the experimental results. The altered Derjaguin-Landau-Verwey
      Overbeek (DLVO) interactions emerging from the contribution of nanoscale
      roughness are theoretically evaluated for each differently rough substrate
      particle combination. The forces have been calculated by considering large- and
      small-scale roughness parameters of the experimental surfaces. The experimental
      findings have been duly corroborated by theoretical estimates. Finally, it is
      observed that the skewness of the surface and the small-scale asperity radius
      bear a correlation with the DLVO forces and subsequently with the ring deposit
      pattern. The present understanding of the influence of surface fluctuations on
      evaporative self-assembly would enable one to choose the right topographic
      surface for particular applications.

PMID- 30299963
TI  - Thiourea-Catalyzed Enantioselective Malonate Addition onto 3-Sulfonyl-3'-indolyl
      2-oxindoles: Formal Total Syntheses of (-)-Chimonanthine, (-)-Folicanthine, and
      (+)-Calycanthine.
AB  - A general approach to bispyrroloindolines via a key thiourea-catalyzed addition
      of malonates to 3-sulfonyl-3'-indolyl-2-oxindoles is reported. The
      enantioselelective process is found to be highly effective (up to 94% ee), where
      a C-C bond formation leads to the synthesis of a number of 2-oxindoles with an
      all-carbon quaternary stereocenter.

PMID- 30299964
TI  - Intermolecular Voids in Lipid Bilayers in the Presence of Glycyrrhizic Acid.
AB  - It is known that glycyrrhizic acid (GA) promotes the enhancement of the activity
      of several medicines. This is attributed to the fact that GA increases the
      membrane permeability of small drug molecules. There is an opinion that GA
      facilitates the formation of additional large voids in the membrane, which
      enhance the passive diffusion of molecules across the membrane. In this work, we
      investigate how GA influences the intermolecular voids using the molecular
      dynamics simulation. We calculate the interstitial spheres (empty spheres
      inscribed between molecules) in model DPPC and DOPC bilayers, both pure and with
      the addition of cholesterol. It was observed that the addition of GA does not
      lead to the formation of new large interstitial spheres; i.e., new large voids do
      not appear. The distribution of empty volume inside the bilayers is also studied.
      We calculated the profiles of the empty volume fraction both from the middle
      plane of the bilayer and from its outer surface (from the lipid-water interface).
      This analysis has shown that the addition of GA does not cause the increase of
      the empty volume in the bilayer; moreover, there is a slight decrease in the
      bilayers with cholesterol. Thus, we have not found a confirmation of the simplest
      hypothesis that individual GA molecules induce pores in the membrane.

PMID- 30299965
TI  - Ranking in Vitro Dissolution of Inhaled Micronized Drug Powders including a
      Candidate Drug with Two Different Particle Sizes.
AB  - Pulmonary dissolution of poorly soluble drug substances (DSs) may limit the drug
      absorption rate and consequently influence clinical performance. Dissolution rate
      is thus an important quality attribute, and its influence on in vivo drug release
      must be characterized, understood, and controlled early in the development
      process. The aim of this study is to establish an in vitro dissolution method
      with the capability to capture therapeutically relevant differences in the
      dissolution rate between drug batches and drug compounds. A method was developed
      by which a biorelevant aerosol fraction was captured on a filter using a
      sedimentation technique in a modified Andersen cascade impactor to avoid particle
      agglomeration. Subsequently, the filters were transferred to a commercial
      Transwell system where dissolution in 3 mL of phosphate buffer at pH 6.8 with
      0.5% sodium dodecyl sulfate (SDS) occurred at sink conditions. Dissolved DS was
      quantified over time using UPLC-UV. Dissolution data was obtained on a series of
      micronized and aerosolized lipophilic DSs, budesonide, fluticasone furoate (FF),
      fluticasone propionate (FP), and AZD5423. The latter is a lipophilic AstraZeneca
      development compound available in two different mass median diameters (MMD), 1.3
      (AZD54231.3) and 3.1 MUm (AZD54233.1). Dissolution data were evaluated using a
      Weibull fit and expressed as t63, the time to dissolution of 63% of the initial
      dose. The following rank-order of t63 was obtained (mean t63 and MMD in
      brackets), budesonide (10 min, 2.1 MUm) = AZD54231.3 (10 min, 1.3 MUm) <
      AZD54233.1 (19 min, 3.1 MUm) < FP (38 min, 2.4 MUm) < FF (63 min, 2.5 MUm). The
      method could differentiate between different drug compounds with different
      solubility but similar particle size distribution, as well as between the same
      drug compound with different particle size distributions. Furthermore, a relation
      between the in vitro dissolution rate ( t63) and mean pulmonary absorption time
      in man (literature data) was observed, indicating clinical relevance. It is thus
      concluded, that the method may be useful for the characterization and ranking of
      DSs and drug products in early development, as well as being a potential tool for
      the control of dissolution as a potential quality attribute.

PMID- 30299966
TI  - Counterion-Induced Nanosheet-to-Nanofilament Transition of Lyotropic Bent-Core
      Liquid Crystals.
AB  - The smart flexibility of phase transitions in liquid crystals (LCs) makes them
      suitable for various applications and is an important research field in
      contemporary science, engineering, and technology. Unlike most reports focused on
      bent-core LCs in the thermotropic situation, in our present study, we designed
      and synthesized a fully rigid bent-core molecule with the sulfonic acid group
      replacing conventional flexible chains. A rich variety of counterion-induced
      supramolecular LC phase behaviors have been systematically investigated. It was
      found that the smectic phase with nanosheets tends to transform to the hexagonal
      phase with nanofilaments when the protons of the sulfonic acid group are
      partially replaced by alkali metal ions. The experimental results show that the
      nanoaggregate and phase transition are controlled by the displacing ratio of
      alkali metal ions rather than the molecular concentration. Another interesting
      feature is that the achiral bent-core molecules self-assemble into columns by
      helical stacking and present macroscopic chirality, indicating that spontaneous
      chiral symmetry breaking occurs in the columnar phase. The fully rigid bent-core
      molecules reveal surprisingly hierarchical molecular self-assemblies with the
      smectic-to-hexagonal phase transition, which was not previously observed in
      supramolecular complexes. The findings will provide new possibilities for
      applications in LC-based photonic devices, biosystem switches, and supramolecular
      actuators.

PMID- 30299967
TI  - Esterase-Sensitive Glutathione Persulfide Donor.
AB  - An esterase-sensitive glutathione persulfide (GSSH) donor (BW-GP-401) is
      described. The release profile was studied by monitoring the formation of lactone
      and direct trapping of GSSH with 1-fluoro-2,4-dinitrobenzene (DNFB). The donor
      was examined for its inhibitory effect toward glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH). Under highly oxidative conditions, the donor also shows
      cytoprotective effects in H9c2 cardiomyocytes.

PMID- 30299968
TI  - Impact of Asphaltene Surface Energy on Stability of Asphaltene-Toluene System: A
      Parametric Study.
AB  - Asphaltene is a complex macromolecule whose abundance strongly affects the
      physical and interfacial properties of crude oil. Asphaltene molecules may
      precipitate during crude oil production/transportation, which may lead to
      plugging/clogging of wellbores, pipelines, and equipment. In this study, the
      solubility of asphaltene in toluene has been investigated by calculation of
      noncovalent interaction energies between asphaltenes in toluene medium. The
      results of this study revealed that the main interactions in the asphaltene
      toluene system are Lifshitz-van der Waals and Lewis acid-base interactions,
      whereas the electrostatic double layer is of lower comparative order of
      significance specifically at lower separation distances and lower zeta
      potentials. However, the repulsive electrostatic double-layer interactions may
      assist in stabilizing the asphaltene-toluene system based on the comparative
      values of Lifshitz-van der Waals, Lewis acid-base, and electrostatic double-layer
      interactions. This is the case especially at higher separation distances and/or
      higher temperatures where asphaltene particles have greater values of zeta
      potential. Furthermore, it is illustrated that when asphaltene has a lower
      electron-donor parameter, i.e., a lower basicity than toluene, then Lewis acid
      base interactions between asphaltenes in toluene are repulsive. This repulsive
      Lewis acid-base interaction may compensate for the attractive van der Waals
      interactions between asphaltene particles at low asphaltene basicity. Finally,
      the electron donor/acceptor component of the surface energy strongly determines
      the fate of asphaltene in crude oil colloidal system.

PMID- 30299969
TI  - Evaluating the Effect of Shear Stress on Graft-To Zwitterionic Polycarboxybetaine
      Coating Stability Using a Flow Cell.
AB  - The effect of surface coatings on the performance of antifouling activity under
      flow can be influenced by the flow/coating interactions. This study evaluates the
      effect of surface coatings on antifouling activity under different flows for the
      analyses of coating stability. This was done by exposing DOPA-PCB-300/dopamine
      coated polydimethylsiloxane (PDMS) to physiological shear stresses using a
      recirculation system which consisted of dual chamber acrylic flow cells, tygon
      tubing, flow probe and meter, and perfusion pumps. The effect of shear stress
      induced by phosphate buffered saline flow on coating stability was characterized
      with differences in fibrinogen adsorption between control (coated PDMS not loaded
      with shear stress) and coated samples loaded with various shear stresses.
      Fibrinogen adsorption data showed that relative adsorption on coated PDMS that
      were not exposed to shear (5.73% +/- 1.97%) was significantly lower than uncoated
      PDMS (100%, p < 0.001). Furthermore, this fouling level, although lower, was not
      significantly different from coated PDMS membranes that were exposed to 1 dyn/cm2
      (9.55% +/- 0.09%, p = 0.23), 6 dyn/cm2 (15.92% +/- 10.88%, p = 0.14), and 10
      dyn/cm2 (21.62% +/- 13.68%, p = 0.08). Our results show that DOPA-PCB
      300/dopamine coatings are stable, with minimal erosion, under shear stresses
      tested. The techniques from this fundamental study may be used to determine the
      limits of stability of coatings in long-term experiments.

PMID- 30299970
TI  - Colloidal Stability of Apolar Nanoparticles: Role of Ligand Length.
AB  - Inorganic nanoparticle cores are often coated with organic ligands to render them
      dispersible in apolar solvents. However, the effect of the ligand shell on the
      colloidal stability of the overall hybrid particle is not fully understood. In
      particular, it is not known how the length of an apolar alkyl ligand chain
      affects the stability of a nanoparticle dispersion against agglomeration. Here,
      small-angle X-ray scattering and molecular dynamics simulations have been used to
      study the interactions between gold nanoparticles and between cadmium selenide
      nanoparticles passivated by alkanethiol ligands with 12-18 carbons in the solvent
      decane. We find that increasing the ligand length increases colloidal stability
      in the core-dominated regime but decreases it in the ligand-dominated regime.
      This unexpected inversion is connected to the transition from ligand-dominated to
      core-dominated agglomeration when the core diameter increases at constant ligand
      length. Our results provide a microscopic picture of the forces that determine
      the colloidal stability of apolar nanoparticles and explain why classical colloid
      theory fails.

PMID- 30299971
TI  - Palladium(II)-Catalyzed C(sp2)-H Carbonylation of Sterically Hindered Amines with
      Carbon Monoxide.
AB  - A palladium-catalyzed, amine-directed C(sp2)-H carbonylation of alpha,alpha
      disubstituted benzylamine under 1 atm of CO for the facile synthesis of
      sterically hindered benzolactam has been developed. The key to success is the use
      of 2,2,6,6-tetramethyl-1-piperidinyloxy as the crucial sole oxidant. The
      synthetic utility of this transformation has been demonstrated by the first
      concise synthesis of the natural product spiropachysin-20-one.

PMID- 30299972
TI  - Intramolecular Desulfitative Coupling: Nickel-Catalyzed Transformation of Diaryl
      Sulfones into Biaryls via Extrusion of SO2.
AB  - As a new transformation of organosulfur compounds, intramolecular desulfitative
      coupling of diaryl sulfones to the corresponding biaryls has been developed with
      the aid of nickel-NHC catalysts. This catalytic elimination of SO2 was also
      applicable to alkenyl aryl sulfone to furnish the corresponding alkenyl arene.

PMID- 30299973
TI  - Authors' reply.

PMID- 30299974
TI  - Effect of Lactation on Maternal Hypertension: A Systematic Review.
AB  - INTRODUCTION: Hypertension is relatively common in pregnancy, and pregnancy may
      unmask hypertension among women who are predisposed to it. Lactation may be a
      means through which to mitigate pregnancy-related vascular risk. The impact of
      lactation on maternal blood pressure, and the duration of any effect, remains
      unclear. This study aimed at systematically reviewing the literature evaluating
      the impact of lactation on the development of hypertension. MATERIALS AND
      METHODS: We searched PubMed, including EMBASE and MEDLINE, for studies that
      reported on the association between breastfeeding and maternal risk of
      hypertension that were published in a peer-reviewed source. The quality of the
      studies included was assessed by using the Newcastle-Ottawa Scale. RESULTS:
      Nineteen studies met all inclusion criteria for this review. Of the four studies
      with short-term follow-up, 50% showed a protective association. The fifteen
      studies with longer-term follow-up were stratified by outcome assessed. Sixty
      seven percent of the studies that evaluated for elevated blood pressure and 100%
      of the studies evaluating for an outcome of hypertension showed a protective
      association. The minimum duration of lactation associated with a benefit was 1
      month. This association was demonstrated in follow-up periods as long as two to
      three decades. Studies that showed a protective association had overall higher
      quality ratings. DISCUSSION: Lactation is associated with a beneficial effect on
      maternal blood pressure that persists for decades. These results add to the
      growing body of literature demonstrating the protective association of lactation
      on maternal cardiovascular risk. Providers may incorporate the decreased risk of
      hypertension into their counseling on the maternal benefits of lactation.

PMID- 30299975
TI  - Executive Functioning Mediates Predictions of Youth Academic and Social
      Development from Parenting Behavior.
AB  - Using multiple mediation with bootstrapping, dimensions of executive functioning
      (i.e., inhibitory control, working memory, set shifting) were tested as mediators
      of predictions of academic and social outcomes from observed positive and
      negative parenting in 131 children followed prospectively into early adolescence.
      Inhibitory control and working memory mediated predictions of academic
      achievement, whereas inhibitory control meditated predictions of school
      competence from positive parenting. Additionally, working memory mediated
      predictions of negative social preference, but not social competence, from
      positive parenting. Executive functioning did not mediate predictions from
      negative parenting. The role of parenting in shaping youth outcomes through
      executive functioning is considered.

PMID- 30299976
TI  - In-Clinic Evaluation of the MiniMed 670G System "Suspend Before Low" Feature in
      Children with Type 1 Diabetes.
AB  - BACKGROUND: The Medtronic predictive low-glucose management (PLGM) algorithm
      automatically stops insulin delivery when sensor glucose (SG) is predicted to
      reach or fall below a preset low-glucose value within the next 30 min, and
      resumes delivery after hypoglycemia recovery. The present study evaluated the
      PLGM algorithm performance of the MiniMedTM 670G system SmartGuardTM "suspend
      before low" feature in children aged 7-13 years with type 1 diabetes (T1D).
      METHOD: Participants (N = 105, mean +/- standard deviation of 10.8 +/- 1.8 years)
      underwent an overnight in-clinic evaluation of the "suspend before low" feature
      with a preset low limit of 65 mg/dL. After exercise, frequent sample testing
      (FST) was conducted every 5 min if values were <70 mg/dL; every 15 min if 70-80
      mg/dL; and every 30 min if >80 mg/dL. First-day performance of the GuardianTM
      Sensor 3 glucose sensor and continuous glucose monitoring system was also
      evaluated. RESULTS: Activation of the "suspend before low" feature occurred in 79
      of the 105 participants, 79.7% (63/79) did not result in SG falling below 65
      mg/dL. Mean glucose at activation was 102 +/- 19 mg/dL and the initial insulin
      suspension duration was 87.5 +/- 32.7 min. Four hours after insulin resumption,
      mean reference glucose was 130 +/- 42 mg/dL. Mean absolute relative difference
      between the FST reference glucose and SG values on the first day of sensor wear
      was 11.4%. For the 26 participants in whom the "suspend before low" feature did
      not activate, none involved a reference glucose value <=65 mg/dL, suggesting that
      the PLGM algorithm performed as intended. CONCLUSION: In children aged 7-13 years
      with T1D, the "suspend before low" feature of the MiniMed 670G system
      demonstrated a hypoglycemia prevention rate of nearly 80% after exercise and did
      not involve rebound hyperglycemia. There were no events of severe hypoglycemia
      during the evaluation.

PMID- 30299977
TI  - Sexual Distress Mediates the Associations Between Sexual Contingent Self-Worth
      and Well-Being in Women With Genitopelvic Pain: A Dyadic Daily Experience Study.
AB  - Provoked vestibulodynia (PVD), a common cause of women's genitopelvic pain, is
      associated with poorer psychological and sexual well-being in affected couples.
      Greater sexual contingent self-worth (CSW)-defined as self-esteem that is
      dependent on the perceived success or failure of a sexual relationship-has been
      linked to poorer well-being in a cross-sectional study of couples coping with
      PVD. This study aimed to examine whether daily sexual distress mediated the
      associations between greater sexual CSW and lower sexual satisfaction and greater
      anxiety, depressed mood, and women's pain in affected couples. Women (N = 125)
      diagnosed with PVD and their partners completed the Sexual CSW Scale and then
      online daily surveys for eight weeks measuring sexual distress, sexual
      satisfaction, anxiety, depressed mood, and women's pain during intercourse.
      Multilevel analyses were based on the actor-partner interdependence model (APIM).
      For women who had higher sexual CSW (compared to lower sexual CSW), on sexual
      activity days when their sexual distress was higher, they reported lower sexual
      satisfaction and greater anxiety, depressed mood, and pain (compared to their
      average level across all sexual activity days). Findings suggest that daily
      sexual distress may be one pathway between greater sexual CSW and poorer day-to
      day well-being in women with PVD.

PMID- 30299978
TI  - Intrinsic Parameters and Bacterial Growth Prediction in a Brazilian Minimally
      Ripened Cheese (Coalho) during Refrigerated Storage.
AB  - This study evaluated the microbiological and physicochemical characteristics in
      different commercial brands of a Brazilian minimally ripened (coalho) cheese
      during 60 days of storage under refrigeration. Combinations of maximum and
      minimum values of water activity and pH determined in cheese samples at
      refrigeration temperature (7 degrees C) were used in a bacterial growth
      prediction analysis. Maximum growth rate (Grmax) was estimated for different
      pathogenic and/or spoilage bacteria using the ComBase Predictor. Results of
      microbiological characterization analyses showed persistent high counts for all
      monitored microbial groups ( Lactobacillus spp., Lactococcus spp., Enterococcus
      spp., Staphylococcus spp., Enterobacteriaceae, proteolytic and lipolytic
      microorganisms, and fungi) in cheese samples; no dominant microbial group was
      observed over time. Values of pH (6.03 +/- 0.16 to 7.28 +/- 0.55), acidity (0.15%
      +/- 0.09% to 0.66% +/- 0.26%), sodium chloride (1.05% +/- 0.19% to 1.97% +/-
      0.75%), and water activity (0.948 +/- 0.020 to 0.974 +/- 0.012) did not vary in
      cheese samples during storage. Estimated Grmax values for the tested bacteria
      were in the range of 0.004 to 0.044 log CFU/h. Highest Grmax values (0.005 to
      0.044 log CFU/h) were predicted for the psychrotrophic Aeromonas hydrophila,
      Listeria monocytogenes, Pseudomonas spp., and Yersinia enterocolitica. Grmax
      values predicted for Escherichia coli, Salmonella spp., and Staphylococcus aureus
      were in the range of 0.004 to 0.016 log CFU/h. These results indicate
      unsatisfactory microbiological characteristics of commercially available coalho
      cheese. Physicochemical characteristics of commercial coalho cheese stored under
      refrigeration allow bacterial growth to occur, indicating higher risk for fast
      growth of contaminant bacteria in this product.

PMID- 30299979
TI  - Psocoptera (Psocodea) in Spice and Medicinal Dehydrated Plants Sold in Bulk in a
      Big Metropolis in Brazil.
AB  - In Brazil, the production of dried herbs and condiments is on a smaller scale
      than that of its other agricultural sectors; however, it has been growing and
      attracting new producers, driven by the stimulus to provide healthy and gourmet
      foods. Insects in the order Psocoptera may cause loss of quality in such dried
      foods, and because of their small size, these insects can be easily transported
      by commerce. No information is available on how these insects may be entering
      Brazil via the importation of dehydrated products or how they may be exported
      with the increase of Brazilian dried food production. To examine these issues, 10
      sites offering foods sold in bulk within the city of Sao Paulo, Brazil, were
      chosen. At each food site, the same 20 species of aromatic spice and medicinal
      dehydrated plants were purchased. In the laboratory, they were analyzed for the
      presence of insects immediately after acquisition. After removal of nymphal and
      adult psocopterans, the plants were kept in vials under environmental conditions
      to be investigated 40 days later. Psocopterans were found in 12 of the 20
      dehydrated plant species. Eleven psocopteran species were recorded, including six
      species of unidentified Liposcelis. Liposcelis bostrychophila (Badonnel) was
      found in all samples with the presence of insects. The other frequent species
      were Liposcelis entomophila (Enderlein) and Lepinotus reticulatus (Enderlein).
      Lepinotus reticulatus constitutes the first record in Brazil. In total, 1,021
      insects were recorded in the evaluation right after purchase, and this number
      grew to 3,734 individuals recovered 40 days later under laboratory conditions.
      The data show that in a relatively short period of storage, a population increase
      occurs that may cause loss of product quality and a decrease in organoleptic
      properties. Thus, it is necessary to have greater surveillance of the products so
      that consumers have access to quality dehydrated foods.

PMID- 30299980
TI  - Development and Feasibility Testing of a Videogame Intervention to Reduce High
      Risk Sexual Behavior in Black and Hispanic Adolescents.
AB  - OBJECTIVE: Develop and test feasibility of a mobile videogame intervention to
      decrease high-risk sexual behavior in black and Hispanic adolescents. MATERIALS
      AND METHODS: Iterative design to develop intervention in partnership with target
      audience. Feasibility and preliminary impact data collected at baseline,
      following 2-3 hours of gameplay and at 8-week follow-up. RESULTS: Twenty-six 15
      17-year-olds completed pilot testing: 16 (62%) were male, 20 (77%) black or
      Hispanic. Pilot testing demonstrated feasibility, including producing a usable
      videogame prototype, incorporating videogame testing within a high school, and
      participants' acceptability of the videogame. Participants' gameplay experience
      reflected that most would play the videogame again (77%), stated that they felt
      responsible for the choices they made in the videogame (73%), and would tell
      their friends to play the videogame (58%). Most suggested adding more videogame
      content to further engage participants. From baseline to follow-up, participants
      demonstrated improvements in condom and contraception self-efficacy (P = 0.003),
      risk perceptions (P = 0.009), and high-risk sexual behavior knowledge (P <
      0.0001). Among black or Hispanic adolescents, we found improvements in summary
      measures of intentions (P = 0.04), self-efficacy (P = 0.003), risk perceptions (P
      = 0.002), and sexual knowledge (P = 0.0002). Adolescents with previous sexual
      experience showed similar improvements. CONCLUSION: Pilot testing of an
      innovative videogame, developed in partnership with the target audience,
      demonstrated feasibility and preliminary impact with this cohort of black or
      Hispanic adolescents. We developed a usable videogame prototype and gained
      important data about how to enhance the next videogame iteration. Future plans
      include targeting an older age group to maximize our ability to measure potential
      impact among sexually experienced adolescents.

PMID- 30299981
TI  - "I Felt Like I Was a Part of Trying to Keep My Baby Alive": Perspectives of
      Hispanic and Non-Hispanic Black Mothers in Providing Milk for Their Very Preterm
      Infants.
AB  - BACKGROUND: Compared with non-Hispanic white, Hispanic and non-Hispanic black
      mothers of very preterm infants are less likely to provide mother's milk at the
      point of hospital discharge; the perspectives of these mothers are poorly
      understood. OBJECTIVES: To examine the perceived barriers and facilitators of
      providing milk for very preterm infants during the hospitalization among Hispanic
      and non-Hispanic black mothers. MATERIALS AND METHODS: We conducted 23 in-depth,
      semistructured interviews of English and Spanish-speaking Hispanic and non
      Hispanic black mothers that initiated milk production for their very preterm
      infants, <=1,750 g at birth. Following thematic saturation, results were
      validated through expert triangulation and member checking. RESULTS: Twelve
      mothers were Hispanic, where three were English speaking and nine were Spanish
      speaking. Eleven mothers were non-Hispanic black and English speaking. We found
      themes pertaining to general experiences: (1) Breastfeeding intent impacts
      mothers' success in providing milk throughout the hospitalization; (2) Pumping
      milk for a hospitalized infant is repetitive, exhausting, and does not elicit the
      same emotional connection as breastfeeding; (3) Hospital providers are an
      important source of support, when sufficient time is spent to address ongoing
      issues; (4) Providing milk creates a unique sense of purpose when mothers
      otherwise feel a lack of control; and we found themes pertaining to the
      experiences of Hispanic and non-Hispanic black mothers: (1) Breastfeeding as a
      cultural norm influences mothers' intent to initiate and continue breastfeeding;
      (2) Hospital staff are viewed as more supportive when interactions and treatment
      are perceived as racially/ethnically unbiased and (3) when communication occurs
      in the primary language; and (4) Mother-infant separation creates logistical
      challenges that negatively impact ongoing milk production. CONCLUSIONS: While
      providing milk for a hospitalized very preterm infant is exhausting, and
      logistically challenging, Hispanic and non-Hispanic black mothers are inspired to
      do so because of their intent to breastfeed, support from hospital providers, and
      feelings of purpose.

PMID- 30299982
TI  - The Relationship Between Dimensions of Adult Attachment and Motivation for Faking
      Orgasm in Women.
AB  - Attachment and sexual behavior are both integral parts of adult romantic
      relationships. Attachment avoidance is linked to impersonal, egocentric sexual
      activities, whereas the sexuality of anxiously attached individuals revolves
      around relationship maintenance and the needs of the partner. In this attachment
      context, faking orgasm might serve as a means for relational regulation. The aim
      of our study was to investigate the links between dimensions of adult attachment
      and motives for faking orgasm in women. Young women completed measures of adult
      attachment and motivations for faking orgasm. Both attachment avoidance and
      attachment anxiety were related to the use of faked orgasm as a means to avoid
      negative, shameful feelings. Attachment avoidance was significantly associated
      with the intention to quickly end sexual intercourse through faking orgasm.
      Attachment anxiety was associated with the use of faked orgasm to increase sexual
      arousal and to elevate partners' self-esteem. Results are discussed with regard
      to relational and sexual goals associated with adult attachment orientations.

PMID- 30299983
TI  - Evaluation of the dental spectral cone beam CT for metal artefact reduction.
AB  - OBJECTIVES:: Metal artefacts are highly common in dental CT images because of the
      high X-ray attenuation of metallic dental fillings and implants. This study
      presents an evaluation of the virtual monochromatic imaging for metal artefact
      reduction by a recently introduced dental spectral cone beam CT, which is the
      first commercial dental spectral CBCT with flat-panel detector. METHODS:: We
      carried out phantom experiments and clinical trials in this study. In the phantom
      study, the head phantom with metallic dental fillings and implants of various
      materials was scanned. Moreover, standard deviation, metal artefact index, and
      contrast-to-noise ratio were analyzed for fixed region of interest. Patient study
      included 23 patients with metallic fillings and metal implants. Traditional CT
      images and virtual monochromatic images were produced in a single scan, ensuring
      that the comparison can be made within the same patient and same location.
      Standard deviation and metal artefact index were analyzed for fixed region of
      interest. RESULTS:: The phantom study and patient study showed that the metal
      artefacts caused by metallic dental fillings are well-suppressed by the virtual
      monochromatic imaging. Moreover, the improvements in virtual monochromatic
      imaging in terms of image quality are more pronounced for small dental fillings..
      The noise increase in image slices without metallic objects is a side-effect of
      the virtual monochromatic images. CONCLUSIONS:: Virtual monochromatic imaging by
      spectral cone beam CT reduces the metal artefact and improves the image contrast
      to-noise ratio around dental metallic fillings. This kind of imaging would be
      recommended for patients with dental metallic fillings.

PMID- 30299985
TI  - Concussion Competencies: A Framework for School-based Concussion Management.

PMID- 30299984
TI  - Quality Control System in an Obstetrics and Gynecology Disease Biobank.
AB  - AIM: To ensure that sample quality meets the requirements of experimental
      research, the gynecology and obstetrics biobank of the Nanjing Drum Tower
      hospital designed different quality control methods for relevant types of
      samples. A range of quality control procedures has been formulated. METHODS: The
      sample types were frozen tissue, paraffin-embedded tissue, optimal cutting
      temperature (OCT)-embedded tissue, plasma, buffy coat, serum, blood clots, and
      urine. Different categories of samples from a random selection of 1% of cases
      were analyzed for quality control experiments: (i) frozen tissue, buffy coat, and
      blood clots: RNA and DNA were extracted and the concentration, purity, and
      integrity were determined; (ii) paraffin-embedded tissue: morphological
      observations were made after hematoxylin-eosin staining and immunohistochemical
      detection of beta-actin or CD10; (iii) OCT-embedded tissue: hematoxylin-eosin
      staining and immunofluorescence detection of beta-actin; and (iv) frozen tissue
      samples derived from different organs of 18 fetal autopsy specimens with
      different cold ischemia times (CITs), 0-12 hours, 12-18 hours, 18-24 hours, and
      24-48 hours, were chosen to study RNA quality. There is no universally recognized
      quality control index for plasma, serum, and urine, so the quality of samples was
      evaluated from feedback from the research projects in which the samples were
      used. RESULTS: Currently, there are ~2000 cases and 360,000 sample vials in the
      biobank. According to the experiments, (i) the concentration and purity of all
      nucleic acids of selected samples were qualified; (ii) for frozen tissues with a
      CIT <=1 hour, using a qualified standard RNA quality number (RQN) >=7, the
      qualification rate was 90%; (iii) frozen tissues with CIT between 1 and 18 hours,
      using a qualified standard RQN >=5, the qualification rate was 61.1%; (iv) all of
      the paraffin-embedded tissues qualified for morphological observation; (v) the
      qualification rate of OCT-embedded tissue was 89%; and (vi) CIT had a great
      influence on the integrity of frozen tissue RNA. As the tissue CIT lengthened,
      the integrity of the RNA decreased. The RNA integrity parameters of different
      tissue types in the same specimen were significantly different. CONCLUSIONS: A
      quality control system was constructed in an obstetrics and gynecology disease
      biobank with various types of diseases and abundant samples. Using specific
      quality control experiments for different types of samples was a reliable
      operating strategy that can be beneficial for providing qualified research
      resources. For birth defect autopsy specimens, the samples used for RNA research
      should have a CIT of at least <12 hours.

PMID- 30299986
TI  - Quantifying the setup uncertainty of a stereotactic murine micro-image guided
      radiation therapy system.
AB  - OBJECTIVE:: Investigate the reproducibility of murine cranial positioning using
      solely a stereotactic stage, and quantify the potential improvements from the on
      board image guidance of the X-RAD SmART irradiator. METHODS:: For intermouse
      reproducibility, athymic nude mice (N = 5, *4 groups) were cranially fixed on a
      stereotactic stage. Each mouse was imaged via cone-beam CT (CBCT). A virtual
      isocenter target was placed in the brain, the stage shifted to that target, and
      the couch positions recorded. The mouse was removed from the stage and this
      process repeated twice (N=60 measurements). The first acquired CBCT coordinates
      (within each group of five mice) were used to define "stereotactic couch
      coordinates." CBCT shifts were calculated to quantify the accuracy of setup based
      on couch coordinates alone. For intramouse reproducibility, C57BL/6 mice (N=4)
      were imaged daily for 7 days. Each mouse had individual stereotactic coordinates
      defined from their first day of CBCT localization, and positional shifts required
      on the six subsequent days of imaging were quantified (N = 24 measurements).
      RESULTS:: The mean vector shift between stereotactic setup and CBCT alignment for
      inter and intramouse analysis was 0.78 +/- 0.27 mm and 0.82 +/- 0.34 mm,
      respectively. CONCLUSION:: Cranial irradiation that can permit positional
      uncertainties on the order of a millimeter can rely solely on stereotactic
      coordinates derived from a single daily CBCT. Irradiations of subregions
      requiring submillimeter accuracy require daily image guidance for each mouse.
      ADVANCES IN KNOWLEDGE:: This is the first investigation of stereotactic
      reproducibility using the X-RAD SmART and it suggests a method for increased
      efficiency in high-throughput experiments.

PMID- 30299987
TI  - Cognitive and Affective Theory of Mind in Mild Cognitive Impairment and
      Parkinson's Disease: Preliminary Evidence from the Italian Version of the Yoni
      Task.
AB  - The aim of the study was to explore cognitive and affective dimensions of ToM
      using the computerized Yoni task in participants with amnestic Mild Cognitive
      Impairment (aMCI=16), early stage of Parkinson's Disease (PD=14), and healthy
      controls (HC=18) Results demonstrated that the Yoni task was effective in
      discriminating between groups in 1th order cognitive dimension (MCI<PD=HC,
      pcorr<.05), and in 2nd order cognitive and affective dimensions (MCI<HC, pcorr
      <.05), highlighting a reduced ToM performance also in people with PD (MCI<PD<HC,
      pcorr <.05). Thus, the Yoni task represents a sensitive tool for detecting
      different dimensions of ToM impairment, across different clinical conditions.

PMID- 30299988
TI  - Use of iOCT in Vitreoretinal Surgery for Dense Vitreous Hemorrhage in a Chinese
      Population.
AB  - PURPOSE: To evaluate the feasibility and utility of intraoperative optical
      coherence tomography (iOCT) during pars plana vitrectomy (PPV) surgery for dense
      vitreous hemorrhage (VH). METHODS: A retrospective, consecutive, interventional
      case series. A total of 68 dense VH patients (71 eyes) were enrolled, and the
      patients were divided into two groups. The control group (43 eyes) did not
      receive iOCT and the experimental group (28 eyes) did. All patients with macular
      structures that could not be assessed by preoperative OCT underwent PPV for dense
      VH. iOCT images were qualitatively evaluated for retinal abnormalities that might
      affect intraoperative management. The assessment of iOCT utility was evaluated by
      the surgeon. Intraoperative membrane peeling, postoperative macular structure,
      and postoperative visual acuity were compared between the two groups. RESULTS:
      There were no significant differences in sex, age, different etiologies of VH, or
      best corrected visual acuity between the two groups at baseline. In the
      experimental group, iOCT revealed macular edema (eight eyes, 28.6%), epiretinal
      membranes (ERM, five eyes, 17.9%), macular atrophy (one eye, 3.6%), lamellar
      macular hole (one eye, 3.6%), polypoidal choroidal vasculopathy (one eye, 3.6%),
      and the existence of both macular edema with ERM (one eye, 3.6%). Eight cases
      showed macular abnormalities on the iOCT images that were inconsistent with the
      surgeon's judgment without iOCT. iOCT imaging affected the surgical plan for
      seven of the eight cases. Significantly more iOCT eyes had intraoperative
      membrane peeling than control eyes (P = 0.01), while significantly fewer iOCT
      eyes had postoperative ERMs (P = 0.04). CONCLUSIONS: iOCT during PPV for VH may
      provide the surgeon with clinically relevant information that influences surgical
      management. The iOCT group had a higher incidence of ERM peeling intraoperatively
      and lower incidence of ERM postoperatively compared with the control group.

PMID- 30299989
TI  - Will MRI of gastrointestinal function parallel the clinical success of cine
      cardiac MRI?
AB  - Cine cardiac MRI is generally accepted as the "gold-standard" for functional
      myocardial assessment. It only took a few years after the development of
      commercial MRI systems for functional cardiac imaging to be developed, with
      electrocardiogram (ECG)-gated cine imaging first reported in 1988. The function
      of the gastrointestinal (GI) tract is more complex to study compared to the
      heart. However, the idea of having a non-invasive tool to study the GI function
      that also allows the concurrent assessment of different aspects of this function
      has become more and more attractive in the gastroenterological field. This review
      summarises key literature of the last 5 years to describe the current status of
      MRI in respect to the evaluation of GI function, highlighting the gaps and
      challenges and the future prospects. As the clinical application of a new
      technique requires that its clinical utility is confirmed by demonstration of its
      ability to enable clinicians to make a diagnosis and/or predict the treatment
      response, this review also considers whether or not this has been achieved, and
      how MRI has been validated against techniques currently recognised as the gold
      standard in clinical practice.

PMID- 30299990
TI  - Correction.

PMID- 30299991
TI  - Evolution of depression during rehabilitation program in patients with
      cardiovascular diseases.
AB  - BACKGROUND: Cardiovascular diseases represent the main cause of death in the
      world. Rehabilitation through exercise is more and more used in cardiac patients.
      Given that these patients suffer from depressive symptoms, the risk of having
      recurrent cardiovascular problems increases. Thus, the aim of this study is to
      identify the effects of a rehabilitation program on the physiological and
      psychological parameters; with a particular attention on the depression scores
      between the scales. METHODS: Twenty-eight cardiac patients participated in this
      study during a cardiovascular rehabilitation program. They are tested at their
      entry and at their exit with an evaluation of their physical fitness on an
      electromagnetic cycle ergometer and by four depression scales (Beck Depression
      Inventory, Hospital Anxiety and Depression Scale (HADS), Center for Epidemiologic
      Studies - Depression and Geriatric Depression Screening). RESULTS: We observe
      that 21.4-50% of these patients have depressive symptoms, according to depression
      scales. The women have depression scores significantly higher than the men. The
      rehabilitation program improves their maximal oxygen consumption and their
      maximal aerobic power. At the end of the rehabilitation program, our analysis
      identifies a significant decrease in the depression score for the HADS.
      Regardless of the physical deconditioning level and of the improvement of the
      maximal oxygen consumption, our results show an effect of the rehabilitation
      program on the depression scores. No correlation between the physical
      deconditioning and the different depression scores is observed. CONCLUSIONS: This
      study shows the importance of measuring depression and its severity to improve
      the care of patients. Our findings show that between 21.4% and 50% of patients
      have depressive symptoms which challenges the categorical approach of the self
      report depression scales. Implications for rehabilitation Depression and
      cardiovascular diseases have an impact on the patients' physical fitness. The
      rehabilitation program, primarily based around exercise, reduces depressive
      symptoms. As soon as cardiovascular diseases patients enter in a rehabilitation
      program, the depression should be measured by a psychologist. Taking into account
      the depressive symptoms of the patients as soon as their cardiac event occurs
      makes it possible to improve the care of patients.

PMID- 30299992
TI  - An Autumn Docket Heavy On Health Policy.
AB  - A spate of health policy litigation featured a challenge to the individual
      mandate and the entire ACA.

PMID- 30299993
TI  - Pharmacotherapy of type 2 diabetes in patients with chronic liver disease: focus
      on nonalcoholic fatty liver disease.
AB  - INTRODUCTION: Pharmacotherapy used to treat type 2 diabetes mellitus (T2DM) is
      facing a paradigm shift in clinical practice with recent cardiovascular (CV)
      outcome trials having a substantial impact on drug prescription with treatment
      having a more tailored approach. In patients with T2DM, the issue of chronic
      liver disease is multifaceted. However, a clinical evidence is emerging on the
      beneficial effect of antidiabetic medications on nonalcoholic fatty liver disease
      (NAFLD). Areas covered: The authors provide a synopsis on the current and
      upcoming pharmacotherapy for NAFLD, including the challenges with their
      development, focusing on drugs for T2DM. Clinical data on the potential benefits
      and safety issues are assessed with the aim of proposing an individualized
      algorithm for patient management. Both MEDLINE and ClinicalTrials.Gov are used to
      derive the relevant information. Expert opinion: Considering the pivotal role of
      insulin resistance in NAFLD, insulin sensitizers should be the treatment of
      choice. Accordingly, pioglitazone is the only drug with a significant effect on
      liver fibrosis, the driver of disease progression and long-term outcome. Among
      new glucose-lowering drugs, glucagon-like-peptide 1 receptor agonists or sodium
      glucose cotransporter type 2 inhibitors have shown positive effects in phase II
      studies and are qualifying as potential candidates for NAFLD treatment in
      diabetes.

PMID- 30299995
TI  - Histogram Analysis of Adrenal Lesions With a Single Measurement for 10th
      Percentile: Feasibility and Incremental Value for Diagnosing Adenomas.
AB  - OBJECTIVE: Our purpose was to assess whether histogram analysis of adrenal
      lesions from a single measurement of mean attenuation and SD, using a threshold
      of 10% of negative voxels, can replace voxel counting while maintaining
      diagnostic accuracy. MATERIALS AND METHODS: In a 4-year period, 325 adrenal
      lesions were detected on CT examinations of 308 consecutive patients. After
      exclusions, 91 patients with 108 lesions, including 20 malignant lesions and 88
      adenomas (defined by histologic results or follow-up), were enrolled. Two
      observers retrospectively measured lesion size, mean attenuation value, and SD
      attenuation value and generated a pixel histogram. The 10th percentile (P10) was
      obtained from the conventional histogram analysis and was also calculated from
      the following formula: P10 = mean attenuation - (1.282 * SD). Diagnostic
      accuracies of the mean attenuation criterion, histogram analysis, and calculated
      10th percentile were compared. RESULTS: The study group was composed of 74
      patients with 88 adenomas and 17 patients with 20 malignant lesions, including
      seven adrenocortical carcinomas and 13 metastases; 93.1% of histograms showed
      normal distribution. The correlation between histogram analysis and calculated
      10th percentile was 0.9827 and 0.9843 for reader 1 and 2 (p < 0.00001 for both).
      For both readers, sensitivity and specificity of the mean attenuation analysis
      were 65.9% (95% CI, 55.0-75.7%) and 100.0% (95% CI, 83.2-100%). The sensitivity
      and specificity of histogram analysis and calculated 10th percentile were the
      same, 87.5% (95% CI, 78.7-93.6%) and 95.0% (95% CI, 75.1-99.8%), for both
      readers. The increment increase in sensitivity was significant (p < 0.001),
      whereas the decrease in specificity was not (p = 0.15). CONCLUSION: For most
      adrenal lesions, the pixel attenuation has a gaussian distribution, allowing
      estimation of 10th percentile with a single measurement. The accuracy of
      histogram analysis and calculated 10th percentile outperformed the mean
      attenuation as a diagnostic criterion for nonfunctioning adenomas.

PMID- 30299997
TI  - Imaging Evaluation of the Adult Presenting With New-Onset Seizure.
AB  - OBJECTIVE: The purpose of this study is to discuss the evidence supporting the
      use of neuroimaging in adult patients presenting with new-onset seizure.
      CONCLUSION: Unenhanced CT should be the initial imaging examination performed for
      adults presenting with first unprovoked seizure in the acute setting to exclude
      conditions requiring urgent or emergent intervention. MRI has added benefits and
      should be considered for adults presenting acutely for whom the initial CT is
      negative and for those presenting with new-onset seizure in the nonacute setting.

PMID- 30299996
TI  - Maturation-Related Changes in T2 Relaxation Times of Cartilage and Meniscus of
      the Pediatric Knee Joint at 3 T.
AB  - OBJECTIVE: The objective of our study was to use a T2 mapping sequence performed
      at 3 T to investigate changes in the composition and microstructure of the
      cartilage and menisci of the pediatric knee joint during maturation. MATERIALS
      AND METHODS: This retrospective study was performed of MRI examinations of 76
      pediatric knees without internal derangement in 72 subjects (29 boys [mean age,
      12.5 years] and 43 girls [mean age, 13.0 years]) who were evaluated with a
      sagittal T2 mapping sequence. T2 relaxation time values were quantitatively
      measured in eight cartilage subregions and in the medial and lateral menisci.
      Wilcoxon rank sum and Kruskal-Wallis tests were used to analyze the relationship
      between cartilage and meniscus T2 relaxation time values and sex and skeletal
      maturation, respectively. A multivariate linear regression model was used to
      investigate the independent association between cartilage T2 relaxation time
      values and age, weight, and body mass index (BMI [weight in kilograms divided by
      the square of height in meters]). RESULTS: There were no significant sex
      differences (p = 0.26-0.91) in T2 relaxation time values for cartilage or
      meniscus. T2 relaxation time values in each individual cartilage subregion
      significantly decreased (p < 0.001) with progressive maturation. T2 relaxation
      time values in the lateral meniscus significantly increased (p = 0.001) with
      maturation, whereas T2 relaxation time values in the medial meniscus did not
      significantly change (p = 0.82). There was a significant association (p < 0.001)
      between cartilage T2 relaxation time values and age independent of weight and
      BMI, but no significant association between cartilage T2 relaxation time values
      and weight (p = 0.06) and BMI (p = 0.20) independent of age. CONCLUSION:
      Cartilage T2 relaxation time values significantly decreased in all cartilage
      subregions and meniscus T2 relaxation time values significantly increased in the
      lateral meniscus during maturation. These changes in T2 relaxation time values
      reflect age-related changes in tissue composition and microstructure.

PMID- 30299998
TI  - Comparison of Metal Artifact Reduction in Dual- and Single-Source CT: A Vertebral
      Phantom Study.
AB  - OBJECTIVE: The objective of this study was to compare the capability of two
      algorithms for metal artifact reduction and virtual monoenergetic imaging (VME),
      a metal artifact reduction application for dual-source CT. MATERIALS AND METHODS:
      A bovine vertebra phantom with 16 artificial osteolyses and two 20 * 4.5 mm
      stainless steel screws was scanned on two single-source CT scanner and one dual
      source CT scanner at a dose identical to the single-source acquisitions. Datasets
      were reconstructed with a metal artifact reduction algorithm for orthopedic
      implants (O-MAR, Philips Healthcare), an iterative metal artifact reduction
      algorithm (iMAR, Siemens Healthineers), and VME. Blinded to the method used for
      artifact reduction, three independent observers evaluated datasets regarding the
      extent of metal artifacts using a 4-point scale. Depicted osteolyses were counted
      and screw diameters measured for each reconstruction. Interobserver variability
      was evaluated using the Kendall coefficient of concordance for ordinal variables
      and the intraclass correlation coefficient for continuous data. RESULTS: VME
      showed the best metal artifact reduction capability among evaluated methods;
      overall artifacts were rated 1.08 +/- 0.29 for VME, 3.33 +/- 0.65 for iMAR, and
      3.91 +/- 0.29 for O-MAR (p < 0.01). VME resulted in better representation of the
      cortical bone, trabecular structure, and soft tissue compared with the other two
      algorithms. VME provided the most realistic reconstruction of screw diameter.
      However, VME missed osteolyses. Good to almost perfect agreement was achieved for
      nearly all evaluated attributes. CONCLUSION: In our vertebral phantom, VME led to
      the most detailed representation of the osteosynthesis screw, caused the lowest
      amount of artifact, and represented the adjacent tissue best. Thus, VME should be
      considered as an alternative method to evaluate implants when other algorithms
      fail.

PMID- 30299999
TI  - Simulated Dose Reduction for Abdominal CT With Filtered Back Projection
      Technique: Effect on Liver Lesion Detection and Characterization.
AB  - OBJECTIVE: Previous studies have shown the possibility to reduce radiation dose
      in abdominal CT by 25-50% without negatively affecting detection of liver
      lesions. How radiation dose reduction affects characterization of liver
      metastases is not as well known. The objective of this study was to investigate
      how different levels of simulated dose reduction affect the detection and
      characterization of liver lesions, primarily hypovascular metastases. A secondary
      objective was to analyze the relationship between the lesion size and contrast-to
      noise ratio (CNR) and the detection rate. MATERIALS AND METHODS: Thirty-nine
      patients (19 with metastases and 20 without) were retrospectively selected. The
      following radiation dose levels (DLs) were simulated: 100% (reference level),
      75%, 50%, and 25%. Five readers were asked to mark liver lesions and rate the
      probability of malignancy on a 5-grade Likert scale. Noninferiority analysis
      using the jackknife free-response ROC (JAFROC) method was performed as well as
      direct comparison of detection rates and grades. RESULTS: JAFROC analysis showed
      noninferior detection and characterization of metastases at DL75 as compared with
      DL100. However, the number of benign lesions and false-positive localizations
      rated as "suspected malignancy" was significantly higher at DL75. CONCLUSION:
      Radiation dose can be reduced by 25% without negatively affecting diagnosis of
      hypovascular liver metastases. Characterization of benign lesions, however, is
      impaired at DL75, which may lead to unnecessary follow-up examinations. Finally,
      increased image noise seems to affect the detection of small lesions to a degree
      that cannot be explained solely by the reduction in CNR.

PMID- 30300000
TI  - Value of Mammography for Women 30-39 Years Old Presenting With Breast Symptoms.
AB  - OBJECTIVE: The purpose of this study was to determine the performance and added
      value of bilateral mammography in identifying cancers distant from sites of
      presenting breast symptoms in women 30-39 years old. MATERIALS AND METHODS: A
      search identified consecutively registered women 30-39 years old who underwent
      mammography and ultrasound to evaluate focal breast symptoms between June 2006
      and August 2016. Outcomes were determined by imaging and pathologic analysis
      through linkage with a tumor registry. Medical records were reviewed to determine
      the presence of breast cancer risk factors. Lifetime breast cancer risk was
      calculated with the International Breast Cancer Intervention Study model.
      RESULTS: The study included 4426 diagnostic examinations of 3997 women 30-39
      years old. Sixty-eight breast cancers were diagnosed (cancer detection rate, 15.4
      per 1000 examinations). Sixty examinations led to biopsy of a finding distant
      from the presenting symptom site, yielding nine incidental malignancies (positive
      predictive value, 15.0%; incidental cancer detection rate, 2.0 per 1000
      examinations [9/4426]). Among the other 59 cancers diagnosed in the symptomatic
      area, bilateral mammography depicted multicentric or contra-lateral disease in
      seven (11.9%). Average lifetime risk of breast cancer among the 68 women with
      cancer was significantly higher than that among age-matched control subjects
      (22.8% vs 13.1%, p < 0.001); 45 of these 68 women (66.2%) had identifiable risk
      factors. Lifetime risk among the nine women with incidental cancers was higher
      than that of age-matched control subjects, although without statistical
      significance (24.9% vs 13.2%, p = 0.07). CONCLUSION: Bilateral mammographic
      evaluation of women 30-39 years old presenting with breast symptoms yielded an
      additional 2.0 incidental cancers per 1000 examinations. The low added cancer
      yield may support the judicious rather than routine use of mammography in this
      patient cohort.

PMID- 30300001
TI  - Opportunistic Screening for Hereditary Hemochromatosis With Unenhanced CT:
      Determination of an Optimal Liver Attenuation Threshold.
AB  - OBJECTIVE: The purpose of this study was to assess whether a specific liver
      attenuation threshold for unenhanced CT allows both sensitive opportunistic
      detection of unsuspected hereditary hemochromatosis and low overall screening
      test-positive rates. MATERIALS AND METHODS: We used a standard ROI placement
      method on unenhanced CT studies of 3357 consecutive adults (mean age, 57.0 years)
      with no symptoms of liver disease who underwent colorectal screening. Hepatic
      attenuation (in HU) was measured to assess test-positive rates at various liver
      attenuation thresholds. To assess sensitivity, unenhanced hepatic CT attenuation
      was also measured in 12 patients with hereditary hemochromatosis (mean age, 48.3
      years), who were homozygous for the HFE C282Y mutation. All scans were obtained
      at 120 kV. Serum ferritin levels were recorded for the hereditary hemochromatosis
      cohort. RESULTS: Mean liver attenuation +/- SD among screened adults was 59.4 +/-
      12.7 HU, compared with 78.7 +/- 13.1 HU (range, 59-105 HU) in the hereditary
      hemochromatosis cohort (p < 0.001). Screening test-positive rates were 30.6% (n =
      1028) at 65 HU, 8.2% (n = 275) at 70 HU, 1.2% (n = 39) at 75 HU, and 0.2% (n = 7)
      at 80 HU. Corresponding sensitivities for hereditary hemochromatosis at these
      thresholds were 83.3% (10/12) at 65, 70, and 75 HU; and 50.0% (6/12) at 80 HU.
      Serum ferritin levels were elevated in all patients with hereditary
      hemochromatosis (mean, 1678 ng/mL; range, 477-3991 ng/mL). CONCLUSION: An
      unenhanced CT liver attenuation threshold of 75 HU was sensitive (83.3%) for
      hereditary hemochromatosis while maintaining an acceptably low screening test
      positive rate (1.2%). An unexplained liver attenuation of 75 HU or more on
      unenhanced CT should trigger appropriate laboratory investigation for iron
      overload; early intervention with phlebotomy can limit or prevent organ damage in
      patients with hemochromatosis.

PMID- 30300003
TI  - Comparison of Standard Breath-Held, Free-Breathing, and Compressed Sensing 2D
      Gradient-Recalled Echo MR Elastography Techniques for Evaluating Liver Stiffness.
AB  - OBJECTIVE: The objective of our study was to compare standard breath-held, free
      breathing, and compressed sensing (CS) accelerated 2D gradient-recalled echo
      (GRE) MR elastography (MRE) techniques for measuring liver stiffness. SUBJECTS
      AND METHODS: Twenty-five adult volunteers (20 without liver disease and five with
      liver disease) underwent MRE with five different 2D GRE techniques: breath-held;
      free-breathing; and CS with acceleration factors of 1.5, 2, and 3. Four axial
      images were obtained through the mid liver with each technique, and liver
      stiffness measurements (in kilopascals) were made by three blinded readers using
      elastograms with 95% confidence maps. Liver stiffness measurements were compared
      between techniques using repeated-measures ANOVA. Absolute agreement between
      techniques was evaluated for each reader using single-measure intraclass
      correlation coefficients (ICCs). Bland-Altman analyses were performed to assess
      bias between techniques using breath-held MRE as the reference. RESULTS:
      Individual subject mean liver stiffness values ranged from 1.35 to 5.25 kPa for
      the population. There was no significant difference in mean liver stiffness
      values between MRE techniques for readers 1 and 3 (p > 0.05). A significant
      difference (p = 0.02) due to higher stiffness measurements using free-breathing
      MRE was observed for reader 2. There was excellent absolute agreement between MRE
      techniques for each reader (all ICCs > 0.940). Bias between techniques ranged
      from -0.102 to 0.089 kPa for reader 1, -0.119 to 0.121 kPa for reader 2, and 
      0.074 to 0.085 kPa for reader 3. CONCLUSION: Free-breathing and CS accelerated 2D
      GRE MRE techniques yield similar results to the conventional breath-held
      technique with only slight bias and may be useful in pediatric and adult patients
      with limited ability to breath-hold.

PMID- 30300002
TI  - Improving Diagnosis of Primary Prostate Cancer With Combined 68Ga-Prostate
      Specific Membrane Antigen-HBED-CC Simultaneous PET and Multiparametric MRI and
      Clinical Parameters.
AB  - OBJECTIVE: The current study was designed to test the diagnostic performance of
      68Ga-prostate-specific membrane antigen (PSMA) PET and multiparametric MRI along
      with clinical parameters in the characterization of prostatic lesions. MATERIALS
      AND METHODS: Eighty-two men with 63 malignant and 21 benign histologically proven
      prostate lesions who underwent complete clinical workup were included in this
      retrospective study. All patients underwent simultaneous whole-body 68Ga-PSMA
      PET/MRI with dedicated multiparametric MRI. Prostate Imaging-Reporting and Data
      System (PI-RADS) version 2 assessment was used for predicting the likelihood of
      cancer. Uptake of 68Ga-PSMA was recorded by adopting the copy-and-paste function
      of ROIs defined on MR images. ROC and combined ROC analyses were performed to
      test the diagnostic accuracy of individual and combined parameters. Spearman
      analysis was used to assess the correlations. RESULTS: PSMA uptake (maximum
      standardized uptake value) was significantly different among tumors with Gleason
      scores of 7, 8, and 9, with the lowest uptake in tumors with a score of 7 and the
      highest uptake in tumors with a score of 9. There was a significant difference
      between early- and delayed-phase PSMA uptake in malignant prostatic lesions (p <
      0.01). Significant correlations were observed between delayed and differential
      PSMA uptake and PI-RADS category (p < 0.01 and < 0.01, respectively), digital
      rectal examination findings (p = 0.01 and < 0.01, respectively), Gleason score (p
      = 0.05 and < 0.05, respectively), and prostate-specific antigen levels (p = 0.01
      for both). Combined ROC analysis of prostate-specific antigen levels, digital
      rectal examination findings, multiparametric MRI, and differential PSMA uptake
      were able to characterize prostatic lesions with a mean (+/- SD) AUC of 0.94 +/-
      0.03, compared with their individual AUCs of 0.77, 0.70, 0.82, and 0.88.
      CONCLUSION: Gallium-68-PSMA PET combined with multiparametric MRI showed high
      diagnostic accuracy for prostate cancer diagnosis compared with either
      multiparametric MRI or PET alone or with clinical factors (e.g., digital rectal
      examination or prostate-specific antigen level) alone, and the combination
      further improves characterization of prostatic lesions.

PMID- 30300004
TI  - Poststernotomy Complications: A Multimodal Review of Normal and Abnormal
      Postoperative Imaging Findings.
AB  - OBJECTIVE: The purpose of this article is to review the normal postoperative
      appearance of various sternotomy configurations as well as the pathophysiologic
      and imaging characteristics of sternotomy complications on radiographs, MDCT,
      MRI, and scintigraphy. CONCLUSION: Clinical signs of sternotomy complications are
      nonspecific and often overlap with normal postoperative changes. Knowledge of
      normal and abnormal imaging findings is essential to guide management and
      treatment.

PMID- 30300005
TI  - Utility of FDG PET/CT in the Characterization of Sinonasal Neoplasms: Analysis of
      Standardized Uptake Value Parameters.
AB  - OBJECTIVE: We aimed to evaluate the contribution of different standardized uptake
      value (SUV) parameters generated from pretreatment 18F-FDG PET/CT in the
      characterization of sinonasal neoplasms with histopathologic correlations.
      MATERIALS AND METHODS: This retrospective study included 97 consecutive patients
      (58 men, 39 women; age range, 20-93 years; mean age, 62 years) with
      pathologically proven untreated sinonasal neoplasms who underwent FDG PET/CT from
      February 2010 to August 2017. Semiquantitative analysis of primary tumors were
      performed to evaluate the maximum standardized uptake value (SUVmax), mean
      standardized uptake value (SUVmean), and the ratio of the SUVmax of the primary
      tumor to the SUVmean of mediastinal blood pool, which we refer to here as "
      SUVratio." Various sinonasal tumor histopathologic subgroups (n = 14) were
      analyzed. The Kruskal-Wallis test was used to compare the SUVmax, SUVmean, and
      SUVratio with the histopathologic diagnosis. RESULTS: Mean values of SUVmax,
      SUVmean, and SUVratio for the sinonasal neoplasms were 16.6 +/- 9.7 (SD), 8.6 +/-
      5.1, and 5.9 +/- 3.7, respectively, and each parameter was significantly
      different between histopathologic types (p < 0.05). Mean values of SUVmax,
      SUVmean, and SUVratio were higher in sinonasal undifferentiated carcinoma (SNUC)
      than in olfactory neuroblastoma, metastasis, and adenoid cystic carcinoma (p <
      0.05). Mean values of SUVmax and SUVmean were higher in squamous cell carcinoma
      (SCC) than in olfactory neuroblastoma and metastasis (p < 0.05). Also, mean
      SUVmax was higher in SCC and SNUC than in poorly differentiated carcinoma (p <
      0.05). Mean SUVratio was higher in SCC than in small cell carcinoma, olfactory
      neuroblastoma, and adenoid cystic carcinoma (p < 0.05). CONCLUSION: We conclude
      that different SUV parameters from FDG PET/CT can be used as so-called "metabolic
      biopsy" to categorize sinonasal neoplasms into different histopathologic
      subgroups because it can help in the characterization of some of the more common
      subgroups of sinonasal neoplasms. However, we found that there is overlap in FDG
      uptake values among some of the rare histologic subgroups; hence, surgical biopsy
      is still needed for differentiation of histologic subtypes of aggressive
      sinonasal masses.

PMID- 30300006
TI  - Detection of Traumatic Pediatric Elbow Joint Effusion Using a Deep Convolutional
      Neural Network.
AB  - OBJECTIVE: The purpose of this study is to determine whether a deep convolutional
      neural network (DCNN) trained on a dataset of limited size can accurately
      diagnose traumatic pediatric elbow effusion on lateral radiographs. MATERIALS AND
      METHODS: A total of 901 lateral elbow radiographs from 882 pediatric patients who
      presented to the emergency department with upper extremity trauma were divided
      into a training set (657 images), a validation set (115 images), and an
      independent test set (129 images). The training set was used to train DCNNs of
      varying depth, architecture, and parameter initialization, some trained from
      randomly initialized parameter weights and others trained using parameter weights
      derived from pretraining on an ImageNet dataset. Hyperparameters were optimized
      using the validation set, and the DCNN with the highest ROC AUC on the validation
      set was selected for further performance testing on the test set. RESULTS: The
      final trained DCNN model had an ROC AUC of 0.985 (95% CI, 0.966-1.000) on the
      validation set and 0.943 (95% CI, 0.884-1.000) on the test set. On the test set,
      sensitivity was 0.909 (95% CI, 0.788-1.000), specificity was 0.906 (95% CI, 0.844
      0.958), and accuracy was 0.907 (95% CI, 0.843-0.951). CONCLUSION: Accurate
      diagnosis of traumatic pediatric elbow joint effusion can be achieved using a
      DCNN.

PMID- 30300007
TI  - Downstream Costs Associated With Incidental Pancreatic Cysts Detected at MRI.
AB  - OBJECTIVE: The purpose of this study is to assess downstream costs associated
      with pancreatic cysts incidentally detected at MRI. MATERIALS AND METHODS: Two
      hundred patients with an incidental pancreatic cyst detected at MRI were
      identified. Downstream events (imaging, office visits, endoscopic ultrasound
      guided fine-needle aspiration, or chemotherapy) were identified from the
      electronic medical record. Radiologists' recommendations and ordering physician
      management were classified relative to the American College of Radiology (ACR)
      incidental findings committee recommendations. Costs for the downstream events
      were estimated using national Medicare rates and a 3% annual discount rate. Mean
      costs were computed. RESULTS: Estimated downstream costs averaged $460 per cyst
      ($872 per cyst with any follow-up testing). Nine patients had a clinically
      relevant outcome during follow-up (increase in cyst size, development of new
      cyst, or development of pancreatic cancer). Downstream cost per cyst with a
      clinically relevant outcome was $1364. Costs were greater when ordering
      physicians overmanaged ($842) versus when they were adherent ($631) or
      undermanaged ($252) relative to radiologist recommendation. Although costs were
      $252 when ordering physicians undermanaged relative to ACR incidental findings
      committee recommendations, costs were similar when ordering physicians were
      adherent ($811) or overmanaged ($845) relative to ACR incidental findings
      committee recommendations. Costs did not vary significantly according to whether
      radiologists recommended follow-up testing ($317-$491) or whether radiologist
      recommendations were adherent, undermanaged, or overmanaged relative to ACR
      incidental findings committee recommendations ($344-$528). CONCLUSION: The
      findings suggest a role for targeted educational efforts, collaborative
      partnerships, and other initiatives to foster greater adherence to radiologist
      recommendations, including critical test results notification systems, automated
      reminders within electronic health systems, and stronger language within
      radiology reports when no follow-up testing is recommended.

PMID- 30300008
TI  - Venous Malformations: Phleboliths Correlate With the Presence of Arteriovenous
      Microshunts.
AB  - OBJECTIVE: The objective of this study was to identify differences between venous
      malformations (VMs) with arteriovenous (AV) microshunts and VMs without AV
      microshunts. MATERIALS AND METHODS: In this retrospective study, 83 patients with
      untreated VMs of the extremities underwent a prospectively defined MRI protocol
      performed at 3 T. MR images were reviewed to determine localization and extent of
      each VM and tissue involvement. The VM volume and the lesion volume relative to
      body surface were measured. The number of phleboliths within the lesions was
      determined. Using time-resolved MR angiography, the hemodynamic subtype (VM with
      AV microshunts versus VM without AV microshunts) was classified, and the interval
      between the onset of arterial enhancement and lesion enhancement (tonset) was
      measured. Clinical data were reviewed to determine patient demographic
      characteristics, the onset of symptoms, the frequency of thrombophlebitis, and
      the pain score. RESULTS: Of the 83 patients, 56 (67%) presented with AV
      microshunts. The tonset (p <= 0.001), absolute and relative lesion volume (p =
      0.001), and number of phleboliths (p = 0.038) differed significantly between
      these two subgroups. With use of a multivariable regression model, the strongest
      indicator for VM with AV microshunts was the presence of more than two
      phleboliths (odds ratio, 2.80; p = 0.007). No differences were noted regarding
      patient demographic characteristics and history or lesion morphologic features or
      anatomy. CONCLUSION: Occurrence of AV microshunts in untreated VM is a frequent
      phenomenon. This hemodynamic subtype is significantly associated with phleboliths
      and large lesions. The subtypes did not differ in terms of history and clinical
      course.

PMID- 30300009
TI  - Association of the Gross Appearance of Intratumoral Vascularity at MDCT With the
      Carbonic Anhydrase IX Score in Clear Cell Renal Cell Carcinoma.
AB  - OBJECTIVE: The purpose of this study was to determine whether qualitative MDCT
      features are associated with the carbonic anhydrase IX (CAIX) score of clear cell
      renal cell carcinoma (RCC). The CAIX score has been previously found to have
      prognostic significance for disease-free survival, overall survival, and lymph
      node involvement. MATERIALS AND METHODS: A cohort of 105 histologically proven
      clear cell RCCs in patients who underwent preoperative four-phase renal mass MDCT
      was derived from 2001 to 2013. Two genitourinary radiologists evaluated each
      lesion for the gross appearance of intratumoral vascularity, calcification,
      enhancement pattern, necrosis, margin, collecting system invasion, and renal vein
      invasion. Immunohistochemical analysis was used to determine the CAIX score
      (defined as the positive staining percentage multiplied by the staining
      intensity). Logistic and linear regression analyses were performed. RESULTS: In a
      linear regression model controlled for lesion size and stage, the gross
      appearance of intratumoral vascularity had a significant positive association
      with CAIX score (beta = 38.33, p = 0.010). In a logistic regression model
      controlled for lesion size and stage, the gross appearance of intratumoral
      vascularity had an odds ratio of 2.85 (p = 0.019) in differentiating clear cell
      RCCs with a CAIX score of 200-300 from clear cell RCCs with a CAIX score of 0
      199. CONCLUSION: In clear cell RCCs, the gross appearance of intratumoral
      vascularity at MDCT was significantly associated with CAIX score, a
      prognostically significant molecular marker. Current assessment of CAIX score
      requires pathologic tissue sampling and immunohistochemical analysis. A
      noninvasive imaging biomarker that may help predict CAIX score may be of great
      clinical value.

PMID- 30300010
TI  - Angiotensin-(1-7) Contributes to Insulin-Sensitizing Effects of Angiotensin
      Converting Enzyme Inhibition in Obese Mice.
AB  - Angiotensin converting enzyme (ACE) inhibitors reduce body weight, lower blood
      pressure (BP), and improve insulin sensitivity in animal models of
      cardiometabolic syndrome. These effects are generally attributed to reduced
      angiotensin (Ang) II formation; however, these therapies also increase levels of
      Ang-(1-7), a beneficial hormone opposing Ang II actions. We hypothesized this Ang
      (1-7) generation contributes to the insulin sensitizing effects of ACE inhibition
      in obese mice. Adult male C57BL/6J mice were placed on a 60% high fat diet for 11
      weeks. During the last 3 weeks of diet, mice received normal water or water
      containing the ACE inhibitor captopril (50 mg/L) as well as the Ang-(1-7) mas
      receptor antagonist A779 (400 or 800 ng/kg/min) or saline vehicle via
      subcutaneous osmotic mini-pumps. At the end of treatment, arterial BP was
      measured and hyperinsulinemic-euglycemic clamps were performed in conscious obese
      mice receiving vehicle, captopril, captopril plus A779, or A779 (n=6-13/group).
      Captopril reduced body weight (28+/-2 vs. 41+/-2 g saline; p=0.001), lowered
      systolic BP (109+/-6 vs.144+/-7 mmHg saline; p=0.041), and improved whole-body
      insulin sensitivity (steady-state glucose infusion rate: 31+/-4 vs. 16+/-2
      mg/kg/min saline; p=0.001) in obese mice. A779 attenuated captopril-mediated
      improvements in insulin sensitivity (23+/-2 mg/kg/min; p=0.042), with no effect
      on body weight (32+/-2 g; p=0.441) or BP (111+/-7 mmHg; p=0.788). There was no
      effect of A779 alone on cardiometabolic outcomes. These data suggest that insulin
      sensitizing effects of ACE inhibition are in part due to activation of Ang-(1
      7)/mas receptor pathways, and provide new insight into mechanisms underlying the
      positive metabolic effects of these therapies.

PMID- 30300011
TI  - Multi-omics Approach Reveals Metabolic Changes in the Heart at Birth.
AB  - During late gestation, the fetal heart primarily relies on glucose and lactate to
      support rapid growth and development. While numerous studies describe changes in
      heart metabolism to preferentially utilize fatty acids a few weeks after birth,
      little is known about metabolic changes of the heart within the first day
      following birth. Therefore, we used the ovine model of pregnancy to investigate
      metabolic differences between the near-term fetal and the newborn heart. Heart
      tissue was collected for metabolomic, lipidomic, and transcriptomic approaches
      from the left and right ventricles and intraventricular septum in 7 fetuses at
      gestational day 142 and 7 newborn lambs on the day of birth. Significant
      metabolites and lipids were identified using a Student's t-test, while
      differentially expressed genes were identified using a moderated t-test with
      empirical Bayes method (FDR-corrected p<0.10). Single-sample gene set enrichment
      analysis (ssGSEA) was used to identify pathways enriched on a transcriptomic
      level (FDR-corrected p<0.05), while over-representation enrichment analysis (ORA)
      was used to identify pathways enriched on a metabolomic level (p<0.05). We
      observed greater abundance of metabolites involved in butanoate and propanoate
      metabolism, and glycolysis in the term fetal heart and differential expression in
      these pathways were confirmed with ssGSEA. Immediately following birth, newborn
      hearts displayed enrichment in purine, fatty acid, and glycerophospholipid
      metabolic pathways, as well as oxidative phosphorylation with significant
      alterations in both lipids and metabolites to support transcriptomic findings. A
      better understanding of metabolic alterations that occur in the heart following
      birth may improve treatment of neonates at risk for heart failure.

PMID- 30300012
TI  - Leptin contributes to the beneficial effects of insulin treatment in
      streptozotocin-diabetic male mice.
AB  - It was long thought that the only hormone capable of reversing the catabolic
      consequences of diabetes was insulin. However, various studies have demonstrated
      that the adipocyte-derived hormone leptin can robustly lower blood glucose levels
      in rodent models of insulin-deficient diabetes. In addition, it has been
      suggested that some of the metabolic manifestations of insulin-deficient diabetes
      are due to hypoleptinemia as opposed to hypoinsulinemia. Since insulin therapy
      increases leptin levels, we sought to investigate the contribution of leptin to
      the beneficial effects of insulin therapy. To do this we tested insulin therapy
      in STZ-diabetic mice that were either on an ob/ob background or that were given a
      leptin antagonist to determine if blocking leptin action would blunt the glucose
      lowering effects of insulin therapy. We found that STZ diabetic ob/ob mice have a
      diminished blood glucose lowering effect in response to insulin therapy compared
      STZ diabetic controls and exhibited more severe weight loss post STZ-injection.
      In addition, STZ diabetic mice administered a leptin antagonist through daily
      injection or plasmid expression respond less robustly to insulin therapy as
      assessed by both fasting blood glucose levels and blood glucose levels during an
      oral glucose tolerance test. However, leptin antagonism did not prevent the
      insulin-induced reduction in beta-hydroxybutyrate and triglyceride levels.
      Therefore, we conclude that elevated leptin levels can contribute to the glucose
      lowering effect of insulin therapy in insulin-deficient diabetes.

PMID- 30300013
TI  - The rise of transcutaneous drug delivery for the management of alopecia: A review
      of existing literature and an eye towards the future.
AB  - INTRODUCTION: Fractional lasers and microneedling devices are increasingly used
      with topical drugs to treat various conditions, including alopecia, as they grant
      access to dermal structures such as hair follicles and cutaneous vasculature.
      OBJECTIVE: To perform a comprehensive review on transcutaneous drug delivery for
      the management of alopecia. METHODS: PubMed, Embase, and Ovid Medline databases
      were searched using terms including: alopecia, microneedling, lasers,
      androgenetic alopecia (AGA), alopecia areata (AA), drug delivery. Articles were
      examined for inclusion criteria: diagnosis of alopecia regardless of type, use of
      fractional laser or microneedling devices, and subsequent administration of
      topical medication. RESULTS: 8 studies, 6 prospective clinical trials and 2 case
      series, examining either AA or AGA were identified. For AA, five studies examined
      microneedling together with topical triamcinolone in three of these, while two
      studies used photodynamic therapy. Regarding AGA, two studies used topical
      minoxidil plus microneedling, and one examined topical finasteride with
      fractional erbium glass laser. Improvement was seen in 6 of the 8 studies.
      DISCUSSION: Transcutaneous drug delivery via fractional laser and microneedling
      is a promising modality with preliminary evidence for increased hair regrowth
      over topical therapy alone. Further studies are needed to elucidate treatment
      parameters and appropriate device selection for drug delivery.

PMID- 30300014
TI  - Comparison between microwave ablation and bipolar radiofrequency ablation in
      benign thyroid nodules: differences in energy transmission, duration of
      application and applied shots.
AB  - PURPOSE: Comparison between different thermal ablation systems for thyroid
      nodules regarding their different procedural characteristics such as treatment
      time, number of shots and energy transmission in the context of their clinical
      performance such as complication rate and volume reduction after three months.
      METHODS: A total of 60 patients with 65 nodules underwent thermal ablation of
      thyroid nodules with either microwave ablation (MWA) (9 male, 15 female and mean
      age 57 +/- 13 years) or radiofrequency ablation (RFA) (12 male, 24 female and
      mean age 54 +/- 12 years). RESULTS: Mean initial volume (MWA: 23.90 +/- 17.35 ml;
      RFA: 29.44 +/- 30.09 ml), energy transmission (MWA: 13.56 +/- 10.17 kJ; RFA:
      15.12 +/- 13.45 kJ), energy transmission per ml (MWA: 0.85 +/- 1.01 kJ/ml; RFA:
      0.65 +/- 0.32 kJ/ml), power (MWA: 22.69 +/- 12.32 J/s; RFA: 20.97 +/- 7.86 J/s)
      and duration of ablation (MWA: 618 +/- 304 s; RFA: 695 +/- 463 s) were not
      statistically different (p > .05). MWA required significantly less shots (MWA: 3
      +/- 1; RFA: 6 +/- 3) than RFA (p < .05). At three-months follow-up a significant
      mean nodular volume reduction of 53.54 +/- 15.40% after MWA and 51.21 +/- 16.58%
      after RFA (p < .05) was measured. However, mean nodular volume reduction was not
      significantly different between both systems (p > .05). One patient treated by
      MWA reported a transient Horner's syndrome, which recovered without any further
      treatment. Major complications such as nodule rupture, infection or persisting
      nerve injuries did not occur. CONCLUSION: Both systems are suitable to treat
      thyroid nodules and show no significant difference in the duration of
      application, energy transmission and volume reduction. However, MWA requires less
      shots to treat the whole nodule.

PMID- 30300016
TI  - Effects of Carbohydrate, Caffeine and Guarana on Cognitive Performance, Perceived
      Exertion and Shooting Performance in High Level Athletes.
AB  - PURPOSE:: This study aimed at investigating the effect of carbohydrate (CHO),
      caffeine (CAF) and a guarana complex (GUAc) ingestion during a running exercise
      on cognitive performance, ratings of perceived exertion (RPE) and shooting
      performance in high level Modern Pentathlon athletes. METHODS:: Ten athletes
      completed four counterbalanced sessions within a 2 week-period, corresponding to
      ingestions of CHO (30 g), GUAc (300 mg), CAF (200 mg) or placebo (PL). The
      exercise involved a 40-minute run on a treadmill at a steady speed, previously
      determined as a "somewhat hard" exercise (RPE 13). Shooting and cognitive
      performances (Simon task) were assessed in three phases: 1) prior to exercise and
      ingestion, 2) prior to exercise and after half ingestion, and 3) after exercise
      and full ingestion. Ingestions were consumed 40 minutes (250 ml) and 5 minutes
      (125 ml) prior to exercise, and after 20 minutes of run (125 ml). RPE was
      assessed at 10 minutes intervals during exercise. RESULTS:: Results have shown an
      interaction between drinks and exercise on mean reaction time (p = .01, np2= .41)
      and a drinks effect on RPE (p = .01, np2 = .15). CHO, CAF and GUAc enhanced the
      speed of information processing after exercise (respectively p = .003, p = .004
      and p = .04) but only CAF and GUAc decreased RPE (respectively p = .002, p =
      .02). CONCLUSIONS:: Our results highlight the beneficial effect of nutritional
      supplements on information processing and RPE. This finding is particularly
      interesting since decision-making processes are vital in many sports performance.

PMID- 30300015
TI  - Differences in Sprint Mechanical Force-Velocity Profile Between Trained Soccer
      and Futsal Players.
AB  - PURPOSE:: This study aimed to compare the sprint mechanical force-velocity (F-V)
      profile between soccer and futsal players. A secondary aim was, within each
      sport, to study the differences in sprint mechanical F-V profile between sexes
      and players of different levels. METHODS:: 102 soccer players (63 men) and 77
      futsal players (49 men) that were competing from the elite to amateur levels in
      the Spanish league participated in this investigation. The testing procedure
      consisted of 3 unloaded maximal 40-m sprints. The velocity-time data recorded by
      a radar device was used to calculate the variables of the sprint acceleration F-V
      profile (maximal theoretical force [F0], maximal theoretical velocity [V0],
      maximal power [Pmax], decrease in the ratio of horizontal-to-resultant force
      [DRF], and maximal ratio of horizontal-to-resultant force [RFpeak]). RESULTS::
      Futsal players showed a higher F0 than soccer players (effect size [ES] range:
      0.11 to 0.74), while V0 (ES range: -0.48 to -1.15) and DRF (ES range: -0.75 to 
      1.45) was higher for soccer players. No significant differences were observed
      between soccer and futsal players for Pmax (ES range: -0.43 to 0.19) and RFpeak
      (ES range: -0.49 to 0.30). Men and high-level players presented an overall
      enhanced F-V profile compared to women and their lower-level counterparts,
      respectively. CONCLUSIONS:: The higher F0 and lower V0 of futsal players could be
      caused by the specific game's demand (larger number of accelerations but of
      shorter distances compared to soccer). These results show that the sprint
      mechanical F-V profile is able to distinguish between soccer and futsal players.

PMID- 30300017
TI  - Whole-body vibration in the reduction of the cellulite.
AB  - OBJECTIVE: Evaluate the effects of the whole body vibration in improving of
      cellulite in the women's gluteal region. METHODS: Controlled clinical trial
      performed with 42 women, with cellulite in the gluteal region, detected by means
      of clinical examination. After evaluation, the women were divided into two
      groups: Whole-Body Vibration (WBV_G) and control (C_G). The evaluations were
      performed at the beginning and the end of 10 sessions and superficial skin
      temperature, perimetry in the gluteal region, analysis of body contouring,
      analysis of improvement by blind reviewers and instrument of satisfaction, by
      numeric scale were investigated. RESULTS: In the thermographic analysis, the
      WBV_G obtained significant increase of superficial skin temperature on the right
      (p = 0.02) and left (p = 0.02) gluteal region. There was no difference in intra-
      and intergroups in perimetry and the analysis of body contour. The WBV_G obtained
      a higher percentage of improvement by assessment of the blind reviewers (p =
      0.003) and greater aesthetics satisfaction (p = 0.006), when compared to C_G.
      CONCLUSION: WBV provided an improvement in the aspect of the cellulite when
      assessed by blind reviewers and greater participants' satisfaction, providing a
      significant increase in the superficial skin temperature in the gluteal region.

PMID- 30300018
TI  - Neoadjuvant chemotherapy plus radiation versus chemotherapy plus regional
      hyperthermia in high-grade soft tissue sarcomas: a retrospective comparison.
AB  - PURPOSE: Localized adult high-grade soft tissue sarcomas (STS) usually require
      multimodality treatment including surgery, radiotherapy, chemotherapy and
      hyperthermia. If maximal preoperative tumor-shrinkage is envisaged, neoadjuvant
      chemotherapy + radiation (CRT) is often applied, however at the expense of
      relatively high toxicities and increased postoperative complication rates. This
      study aims to compare preoperative CRT with neoadjuvant chemotherapy + regional
      hyperthermia (HCT) regarding histopathological response, toxicity and outcome.
      METHODS: In this retrospective analysis, 61 consecutive high-grade STS patients
      treated between 2009 and 2016 were included. All patients were treated within a
      prospective treatment protocol. 28 patients received neoadjuvant CRT 33 patients
      HCT. CRT consisted of four cycles doxorubicin/ifosfamide and two cycles
      ifosfamide concomitant to 50.4 Gray external beam radiotherapy. HCT consisted of
      4-6 cycles doxorubicin/ifosfamide with deep regional hyperthermia administered bi
      weekly during each cycle. Association of treatment modality with overall survival
      (OS), local control (LC) and freedom from distant metastases (FFDM) was evaluated
      by Kaplan-Meier and log-rank analyses. RESULTS: The overall patient
      characteristics were well balanced. Histopathological tumor response did not
      differ significantly between both groups (p = .67), neither did higher-grade
      toxicities during neoadjuvant treatment. Wound dehiscence (p = .018) and surgical
      hospital re-admissions (p < .001) were both significantly more frequent in the
      CRT group. Two-year OS, LC and FFDM rates of all patients were 93, 85 and 71%
      with no significant differences between CRT and HCT. CONCLUSION: Compared to CRT,
      HCT seems equally efficient and appears to bear less surgical complications.
      Interpretation should be cautious due to the low number of patients and the
      retrospective nature of this study.

PMID- 30300020
TI  - Intense pulsed light vs silicone gel sheet in the management of hypertrophic
      scars: an interventional comparative trial in the Indian population.
AB  - INTRODUCTION: Hypertrophic scars are abnormal scars that are a source of great
      functional, psychological and financial burden to the patient. Currently
      available treatment modalities are either very cumbersome to use or have not
      provided very satisfactory results. Intense pulsed light (IPL) therapy for the
      management of hypertrophic scars has been recently introduced. However, most of
      the studies available are from the Western population. In this trial, we aim to
      study the effect of IPL on the South Indian population with darker skin and
      compare it with an existing treatment modality (silicone gel sheet). MATERIALS
      AND METHODS: This trial was an interventional clinical trial conducted from
      September 2015 to March 2017 on 28 patients with 65 hypertrophic scars. Each scar
      was divided into 2 equal parts (4.6 x 1 cm2). One half of the scar was treated to
      4 sessions of 29J/cm2 of IPL at 3 weekly intervals. A silicone gel sheet (SGS)
      was applied over the other half and changed at 3 weekly intervals. The Vancouver
      scar scale was used to grade both halves of the scar before treatment, at each
      visit and 3 weeks after treatment completion. RESULTS: Scars treated with IPL
      showed a significant reduction in the pliability (p=0.002) and hyperpigmentation
      (p=0.000) as compared to scars treated with SGS. Though the percentage reduction
      in the height of the scar was more in the IPL group (15.4% as compared to 4.6%in
      the SGS group), the result was not statistically significant (p<0.065). As most
      scars in our study showed normal vascularity at the beginning, the percentage
      reduction in vascularity between both groups was the same (p<0.597). The
      reduction in the median VSS score was more in the IPL group compared to SGS group
      (p=0.00). CONCLUSION: IPL therapy offers a safe and effective means of
      hypertrophic scar treatment, especially on large scars where other treatment
      modalities may not be feasible. Minimal side effects that occur can be prevented
      with proper pre, intra and post procedure cooling.

PMID- 30300021
TI  - Randomized, side-by-side comparison of a topical photo-enhancer gel for hair
      removal: an efficacy and safety study.
AB  - BACKGROUND: Novel protocols are evolving to enhance hair follicle damage while
      preserving safety and improving efficacy. OBJECTIVES: The safety and tolerability
      of a 755-nm diode laser was compared to a combined laser with topical photo
      enhancer gel ("combined") versus laser alone ("solo"). METHODS: Twenty women (age
      23-33 years old), Fitzpatrick skin type I-V, were randomized to side-by-side
      comparisons with a laser hair removal protocol. The combined side received
      reduced laser energy compared to the solo side. The laser used in-motion super
      hair removal technology. Subjects received up to four treatments. Subjects were
      assessed at baseline and at 1 and 6 months after the last treatment. RESULTS: At
      the 1-month follow-up, there were no statistical differences in percent hair
      reduction between the combined (81 +/- 16%) versus the solo (77 +/- 15%)
      protocols (p > 0.05). Similarly, at 6-month follow-up, there are no statistical
      differences between the combined (71 +/- 24%) versus the solo (70 +/- 23%)
      treatment protocols (p > 0.05). The average accumulative laser energy in the
      combined side was half of the solo side (4.2 +/- 1.6 vs. 7.6 +/- 2.7 kJ,
      respectively). Pain during the procedure was significantly higher in the solo
      (5.5 +/- 1.8) versus the combined (3.8 +/- 1.7) protocol (p < 0.001). CONCLUSION:
      A laser hair removal paradigm that combines a 755-nm diode laser with a photo
      enhancer gel (reduced kJ protocol) is clinically effective as a solo treatment
      protocol.

PMID- 30300019
TI  - Applying lessons from human papillomavirus vaccines to the development of
      vaccines against Chlamydia trachomatis.
AB  - INTRODUCTION: Chlamydia trachomatis (Ct), the most common bacterial sexually
      transmitted infection (STI), leads to pelvic inflammatory disease, infertility,
      and ectopic pregnancy in women. In this Perspective, we discuss the successful
      human papillomavirus (HPV) vaccine as a case study to inform Ct vaccine efforts.
      Areas covered: The immunological basis of HPV vaccine-elicited protection is high
      titer, long-lasting antibody responses in the genital tract which provides
      sterilizing immunity. These antibodies are elicited through parenteral
      administration of a subunit vaccine based on virus-like particles (VLPs) of HPV.
      We present three lessons learned from the successful HPV vaccine efforts: (1)
      antibodies alone can be sufficient to provide protection from STIs in the genital
      tract, (2) the successful generation of high antibody levels is due to the
      multivalent structure of HPV VLPs, (3) major challenges exist in designing
      vaccines that elicit appropriate effector T cells in the genital tract. We then
      discuss the possibility of antibody-based immunity for Ct. Expert commentary: In
      this Perspective, we present a case for developing antibody-eliciting vaccines,
      similar to the HPV vaccine, for Ct. Basic research into the mechanisms of Ct
      entry into host cells will reveal new vaccine targets, which may be antigens
      against which antibodies are not normally elicited during natural infection.

PMID- 30300022
TI  - Microwave ablation followed by immediate biopsy in the treatment of non-small
      cell lung cancer.
AB  - BACKGROUND: To evaluate the efficacy and safety of microwave ablation (MWA)
      followed by immediate biopsy in the treatment of non-small cell lung cancer
      (NSCLC) and to clarify whether pathology changes can predict treatment responses
      and patient survival. METHODS: Patients with pathologically confirmed NSCLC pre
      ablation were treated with MWA, and immediate biopsy was carried out right after
      ablation in one procedure. Pathology changes were categorized according to the
      pre- and postablation pathology: Group A, same histology type; Group B, paired
      histology type with burning degeneration; Group C, no definite histology type;
      Group D, no definite cancer cells. The internal correlations between pathology
      changes and baseline characteristics, responses to MWA and survival were
      evaluated. RESULTS: A total of 68 patients were enrolled in the study, of which
      19, 28, 11 and 10 patients were classified into Group A, Group B, Group C and
      Group D, respectively. In total, 85.3 and 69.1% patients were diagnosed with
      malignant tumors and the same pathology type, respectively. No significant
      difference in clinical-pathologic characteristics or response to MWA between the
      groups was observed. Upon combining Groups A, B and C, Group D exhibited longer
      progression-free survival (PFS) (Groups A + B + C versus Group D, 11.7 months,
      95% CI 9.6-13.7 versus 26.6 months, 95% CI 19.0-34.2, p = .253) and overall
      survival (OS) (15.9 months, 95% CI 14.2-17.5, versus 29.8 months, 95% CI, 24.3
      35.3, p = .395), although no significant differences were observed. Complications
      were identified in 63 (92.6%), of which 17 (25.0%) patients had major
      complications. CONCLUSIONS: Immediate biopsy post-MWA can distinguish cancer
      cells or histology types in most cases of NSCLC. However, pathology changes pre-
      and postablation could not predict the response to MWA and patient survival.

PMID- 30300023
TI  - Anaerobic Speed Reserve: A Key Component of Elite Male 800m Running.
AB  - PURPOSE:: In recent years (2011-2016), men's 800m championship running
      performances have required greater speed than previous eras (2000-2009). The
      "Anaerobic speed reserve" (ASR) may be a key differentiator of this performance,
      but profiles of elite 800m runners and its relationship to performance time have
      yet to be determined. METHODS:: The ASR - determined as the difference between
      maximal sprint speed (MSS) and predicted maximal aerobic speed (MAS) - of 19
      elite 800m and 1500m runners was assessed using 50m sprint and 1500m race
      performance times. Profiles of three athlete sub-groups were examined using
      cluster analysis and the speed reserve ratio (SRR), defined as MSS/MAS. RESULTS::
      For the same MAS, MSS and ASR showed very large negative (both r=-0.74+/-0.30, +/
      90% confidence limits; very likely) relationships with 800m performance time. In
      contrast, for the same MSS, ASR and MAS had small negative relationships (both r=
      0.16+/-0.54), possibly) with 800m performance. ASR, 800m personal best, and SRR
      best defined the three sub-groups along a continuum of 800m runners, with SRR
      values as follows: 400-800m >=1.58, 800m <=1.57 to >=1.47, and 800-1500m as
      <=1.47 to >= 1.36. CONCLUSIONS:: MSS had the strongest relationship with 800m
      performance, whereby for the same MSS, MAS and ASR showed only small
      relationships to differences in 800m time. Further, our findings support coaching
      observation of three 800m sub-groups, with the SRR potentially representing a
      useful and practical tool for identifying an athlete's 800m profile. Future
      investigations should consider the SRR framework and its application for
      individualised training approaches in this event.

PMID- 30300024
TI  - Reliability and Validity of a Novel Trunk Strength Assessment For High
      Performance Sprint Flatwater Kayakers.
AB  - PURPOSE:: The purpose of the current study was to determine the reliability and
      validity of a novel trunk maximal isometric force assessment involving seven
      different tasks with 200 m times for elite sprint flatwater kayakers. METHODS::
      Ten elite sprint flatwater kayakers, performed a series of maximal isometric
      voluntary contractions (MVCs) on two separate days to assess reliability. MVC
      force was assessed as the participants sat on a modified kayak ergometer and
      applied their maximal isometric force to a uniaxial load cell during seven
      different tasks. The seven tasks of interest were a seated trunk forward flexion
      (FF), bilateral rotational pulls (RTPLL, RTPLR), bilateral rotational pushes
      (RTPSL, RTPSR), and a sport specific bilateral kayak stroke simulation (SIML,
      SIMR). Twenty elite flatwater kayak athletes (10 male, 10 female) participated in
      the validity portion by completing the series of tasks in conjunction with a 200
      m race. RESULTS:: MVC force values ranged from 84 N to 800 N across all
      participants and all tasks. The average coefficient of variation (CV) of the
      seven tasks ranged from 2.4% to 7.7%. Regression analysis showed Pearson
      correlations ranging from -0.84 to -0.22 for both absolute and relative values
      with 200 m performance times. CONCLUSIONS:: MVC force measured in each task was
      considered reliable as a small degree of variance between trials was found. The
      summation of the seven trunk scores showed very strong correlations with on-water
      performance, indicating this assessment is valid for elite sprint kayakers.

PMID- 30300025
TI  - Relationship Between Various Training Load Measures in Elite Cyclists during
      Training, Road Races and Time Trials.
AB  - PURPOSE:: The relationship between various training load (TL) measures in
      professional cycling is not well explored. This study investigates the
      relationship between mechanical energy spent (in kJ), sRPE, LuTRIMP and TSS in
      training, races and time trials (TT). METHODS:: From 4 consecutive years field
      data was collected from 21 professional cyclists and categorized as being
      collected in training, racing or TT's. kJ spent, sRPE, LuTRIMP and TSS were
      calculated and the correlations between the various TL's were made. RESULTS::
      11,655 sessions were collected from which 7,596 sessions had heart rate (HR) data
      and 5,445 sessions had an RPE-score available. The r between the various TL's
      during training was almost perfect. The r between the various TL's during racing
      was almost perfect or very large. The r between the various TL's during TT's was
      almost perfect or very large. For all relationships between TSS and one of the
      other measurements of TL (kJ spent, sRPE and LuTRIMP) a significant different
      slope was found. CONCLUSIONS:: kJ spent, sRPE, LuTRIMP and TSS have all a large
      or almost perfect relationship with each other during training, racing and TT's
      but during racing both sRPE and LuTRIMP have a weaker relationship with kJ spent
      and TSS. Further, the significant different slope of TSS versus the other
      measurements of TL during training and racing has the effect that TSS collected
      in training and road-races differ by 120% while the other measurements of TL (kJ
      spent, sRPE and LuTRIMP) differ by only 73%, 67%, and 68% respectively).

PMID- 30300026
TI  - The assessment of the effects of the combination of microdermabrasion and
      cavitation peeling in the therapy of seborrhoeic skin with visible symptoms of
      acne punctata.
AB  - OBJECTIVE: The aim of this study was to assess objectively the effects of the
      combination of corundum microdermabrasion and cavitation peeling in the therapy
      of seborrheic skin with visible symptoms of acne punctata. MATERIAL AND METHODS:
      The study involved a group of nine women. A series of six treatments with the
      combination of microdermabrasion and cavitation peeling were performed within
      facial skin at 10-14 days intervals. Corneometric measurements examining skin
      hydration level and sebumetric measurements analyzing skin sebum level were made
      before the series of treatments and after second, fourth and sixth procedure in
      five facial areas. Clinical assessment of the efficacy of the therapy was
      performed on the basis of photographic documentation (Fotomedicus). Anonymous
      questionnaires were used in order to evaluate patients' satisfaction rate.
      RESULTS: Statistically significant improvement in skin sebum level was observed
      in all examined areas (forehead p = 0.002; nose p = 0.001, chin p = 0.01, left
      cheek p = 0.009, right cheek p = 0.007). In case of skin hydration, significant
      improvement was found only in the area of chin (p = 0.03). 78% of participants
      estimated that the improvement was in the range of 55-70%, while 22% of
      participants of 75-100%. The reduction in the amount and visibility of comedones
      and pimples were demonstrated on the basis of questionnaire and photographic
      documentation. CONCLUSIONS: Combined microdermabrasion and cavitation peeling
      treatments improve the condition of seborrheic skin.

PMID- 30300027
TI  - Suppression of SESN1 reduces cisplatin and hyperthermia resistance through
      increasing reactive oxygen species (ROS) in human maxillary cancer cells.
AB  - INTRODUCTION: Cisplatin is used as a standard chemotherapeutic agent for head and
      neck cancer treatment. However, some head and neck cancers have cisplatin
      resistance, leading to difficulty in treatment and poor prognosis. Overcoming
      cisplatin resistance remains an important strategy to improve prognoses for head
      and neck cancer patients. OBJECTIVE: Elucidation of the mechanisms underlying
      cisplatin resistance can suggest novel targets to enhance the anticancer effects
      of cisplatin for treating head and neck cancers. MATERIAL AND METHODS: We used a
      cisplatin-resistant human maxillary cancer cell line, IMC-3CR to analyse the
      cisplatin resistance mechanisms. Cisplatin-induced genes were analysed in IMC-3CR
      cells using PCR array. Among the genes with expression increased by cisplatin, we
      specifically examined SESN1. SESN family reportedly regenerates peroxiredoxin and
      suppresses oxidative DNA injury by reactive oxygen species (ROS), which can be
      induced by chemotherapeutic agents such as cisplatin, radiation, and
      hyperthermia. The function of SESN1 in cisplatin resistance and ROS generation
      were analysed using specific RNAi. RESULTS: Results show that SESN1 was induced
      by cisplatin treatment in IMC-3CR cells. Suppression of SESN1 by RNAi induced
      apoptosis and reduced cell viability through enhancement of ROS after cisplatin
      treatment. Moreover, suppression of SESN1 enhanced the cell-killing effects of
      hyperthermia with increased ROS, but did not affect the cell-killing effects of
      radiation. CONCLUSIONS: This study demonstrated the participation of SESN1 in
      cisplatin and hyperthermia resistance of human head and neck cancers. SESN1 is a
      novel molecular target to overcome cisplatin resistance and hyperthermia
      resistance and improve head and neck cancer treatment.

PMID- 30300028
TI  - Predictive value of simulated SAR and temperature for changes in measured
      temperature after phase-amplitude steering during locoregional hyperthermia
      treatments.
AB  - INTRODUCTION: On-line adaptive hyperthermia treatment planning can be useful to
      suppress treatment limiting hot spots and improve tumor temperatures during
      locoregional hyperthermia. This requires adequate prediction of changes in
      heating patterns after phase-amplitude steering. We investigated the predictive
      value of simulated SAR and temperature for changes in measured temperature after
      phase-amplitude steering during locoregional hyperthermia. METHODS: All treatment
      sessions of 75 patients with pelvic malignancies treated between September 2013
      and March 2018 were evaluated. Phase-amplitude adaptations during the 60 min
      steady-state period were analyzed. Treatment planning was performed using
      Plan2Heat, based on CT scans with (thermometry) catheters in the vagina, rectum,
      and bladder in situ. The predicted SAR and temperature along the thermometry
      tracks were extracted from the simulated distributions. Correlations between
      changes in average measured temperature and the simulated SAR and temperature
      were evaluated for single phase-amplitude steering events, unaccompanied by other
      (steering) actions. RESULTS: A total of 67 phase-amplitude steering events were
      suitable for analysis. Simulated changes in both SAR and temperature correlated
      with the measured temperature changes. For the vagina, R2 = 0.44 and R2 = 0.55
      for SAR and temperature, respectively. For the rectum, these values were 0.53 for
      SAR and 0.66 for temperature. Correlations for the bladder were weaker: R2 = 0.15
      and R2 = 0.14 for SAR and temperature, respectively. This can be explained by
      convection in the bladder fluid, unaccounted for by present treatment planning.
      CONCLUSION: Treatment planning can predict changes in an average temperature
      after phase-amplitude steering. This allows on-line support with phase-amplitude
      steering to optimize hyperthermia treatments.

PMID- 30300029
TI  - Treading the beaten path with old and new obstacles: a report from the Indian
      HIPEC registry.
AB  - BACKGROUND: The Indian HIPEC registry is a self-funded registry instituted by a
      group of Indian surgeons for patients with peritoneal metastases (PM) undergoing
      surgical treatment. This work was performed to  * Evaluate outcomes of
      cytoreductive surgery +/- HIPEC in patients enrolled in the registry.  * Identify
      operational problems. METHODS: A retrospective analysis of patients enrolled in
      the registry from March 2016 to September 2017 was performed. An online survey
      was performed to study the surgeons' attitudes and existing practices pertaining
      to the registry and identify operational problems. RESULTS: During the study
      period, 332 patients were enrolled in 8 participating centres. The common
      indication was ovarian cancer for three centres and pseudomyxoma peritonei for
      three others. The median PCI ranged from 3 to 23. A CC-0/1 resection was obtained
      in 94.7%. There was no significant difference in the morbidity (p = .25) and
      mortality (p = .19) rates between different centres. There was a high rate of
      failure-to-rescue (19.3%) patients with complications and the survival in
      patients with colorectal PM was inferior. A lack of dedicated personnel for data
      collection and entry was the main reason for only 10/43 surgeons contributing
      data. The other problem was the lack of complete electronic medical record
      systems at all centres. CONCLUSIONS: These results validate existing practices
      and identify country-specific problems that need to be addressed. Despite
      operational problems, the registry is an invaluable tool for audit and research.
      It shows the feasibility of fruitful collaboration between surgeons in the
      absence of any regulatory body or funding for the project.

PMID- 30300030
TI  - Post-sauna recovery enhances brain neural network relaxation and improves
      cognitive economy in oddball tasks.
AB  - OBJECTIVE: The aim of this study was to investigate the post-sauna residual
      consequences on brain neural network arousal, information processing and
      cognitive performance. METHODS: Sixteen male subjects (24 +/- 1 yr.) participated
      in the study. Whole-body hyperthermia was induced with Finnish sauna bathing.
      Before and 90 min after the sauna, resting electroencephalography (EEG) for
      spectral analysis and EEG event-related potentials (ERPs) during oddball tasks by
      two modalities (auditory and visual) were recorded. RESULTS: Sauna bathing
      increased rectal temperature (Tre, 37.11 +/- 0.33  degrees C to 38.84 +/- 0.32 
      degrees C) and heart rate (HR, 65.63 +/- 9.39 bpm to 151.0 +/- 21.8 bpm). At 90
      min after the sauna, Tre (37.00 +/- 0.29  degrees C) and HR (72.1 +/- 2.80 bpm)
      recovered to baseline levels. An increase was found in alpha power following
      sauna recovery. In the visual task modality, post-sauna recovery led to
      enhancement in the N2 amplitude with centroparietal distribution and decreases in
      P3 amplitude with distribution along the frontoparietal axis for executive motor
      cognitive processing. In the auditory task modality, post-sauna recovery led to a
      decrease in P3 amplitude with a frontoparietal distribution and this change was
      accompanied by auditory N2 amplitude enhancement along the centroparietal
      distribution for non-target cognitive processing. No significant differences in
      task performance were found. CONCLUSION: Post-sauna recovery to normothermia led
      to enhanced resting neural network relaxation followed by increases in cognitive
      processing economy for the given oddball tasks. The auditory processing was not
      affected more by post-sauna recovery than was visual processing. Post-sauna
      recovery modifications in ERP components (stimulus processing) were insufficient
      to affect cognitive performance in both visual and auditory task modalities.

PMID- 30300031
TI  - Factors Affecting Cyclists' Chances of Success in Match-Sprint Tournaments.
AB  - PURPOSE:: To further the understanding of elite athlete performance in complex
      race environments by examining the changes in cyclists' performances between solo
      time trials and head-to-head racing in match-sprint tournaments. METHODS::
      Analyses were derived from official results of cyclists in 61 elite international
      sprint tournaments (2000-2016), incorporating the results of 2060 male and 1969
      female head-to-head match races. Linear mixed modelling of log-transformed
      qualification and finish ranks was used to determine estimates of performance
      predictability as intraclass correlation coefficients. Correlations between
      qualifying performance and final tournament rank were also calculated. Chances of
      winning head-to-head races were estimated adjusting for the difference in the
      cyclists' qualifying times. All effects were evaluated using magnitude-based
      inference. RESULTS:: Minor differences in predictability between qualification
      time-trial and final tournament rank were suggestive of more competitiveness
      amongst males in the overall tournament. Performance in the qualification time
      trial was strongly correlated with, but not fully indicative of, performance in
      the overall tournament. Correspondingly, being the faster qualifier had a large
      positive effect on the chances of winning a head-to-head race, but small
      substantial differences between riders remained after adjustment for time-trial
      differentials. CONCLUSIONS:: The present study provides further insight into how
      real-world competition data can be used to investigate elite-athlete performance
      in sports where athletes must directly interact with their opponents 1,2. For
      elite match-sprint cyclists, qualifying time-trial performance largely determines
      success in the overall tournament, but there is evidence of a consistent match
      race ability that modifies chances of winning head-to-head races.

PMID- 30300032
TI  - Comparison of CT/MRI-CEUS and US-CEUS fusion imaging techniques in the assessment
      of the thermal ablation of liver tumors.
AB  - PURPOSE: To compare the applicability of fusion imaging between contrast-enhanced
      ultrasound (CEUS) and computed tomography (CT) or magnetic resonance imaging
      (MRI) (CT/MRI-CEUS fusion imaging) and fusion imaging between CEUS and ultrasound
      (US-CEUS fusion imaging) in the assessment of treatment response during liver
      cancer ablation. METHODS: From August to December 2015, patients who underwent US
      guided thermal ablation of liver tumors at our hospital with available CT/MRI
      images were enrolled consecutively. Both CT/MRI-CEUS and US-CEUS fusion imaging
      were performed in all patients to evaluate treatment responses. The applicable
      rate, success rate of registration and duration time were recorded. Complications
      were monitored in the follow-up period, and CECT/MRI within three months were
      taken as the standard reference of technical efficacy. RESULTS: A total of 157
      liver tumors (19 +/- 8 mm, range 8-55 mm) in 115 patients (54 +/- 11 years old,
      range 2 7~ 84 years old) were enrolled. The applicable rate of US-CEUS fusion
      imaging was 61.1% (96/157) because of inconspicuous lesions in US, lower than
      that of CT/MRI-CEUS fusion imaging (99.7% (155/157)) (p < .05). However, the
      success rate of registration in US-CEUS fusion imaging (93.8% (90/96)) was
      superior to that of CT/MRI-US fusion imaging (81.3% (126/155)) (p < .05),
      especially for cases combined with alternative preablation surgeries or
      procedures (p < .05). The technical efficacy rate was 99.3% (150/151) according
      to the CECT/CEMRI. CONCLUSIONS: Both CT/MRI-CEUS and US-CEUS fusion imaging are
      feasible means for intraprocedural immediate evaluation of treatment response for
      liver thermal ablation. US-CEUS fusion imaging is preferred because of its
      convenience and higher success rate of registration.

PMID- 30300033
TI  - Evidence of metabolic imbalance and oxidative stress among patients suffering
      from pressure ulcers.
AB  - BACKGROUND: Pressure ulcers (PU) are serious medical problems that involve
      several factors. Recent studies suggest that oxidative stress along with chronic
      inflammation may cause and develop PU. However, the metabolic disturbances
      underlying PU are not totally known. The purpose of this study is to evaluate
      biochemical oxidative stress markers in Tunisian patients suffering from PU.
      METHODS: A total of 100 adult patients with PU and 213 healthy adult controls
      were selected for the study. Biochemical parameters related to immune profiles,
      and biomarkers of the liver, kidney, and inflammatory proteins were evaluated
      using recently developed automated measurement methods. Oxidant-antioxidant
      system markers (malondialdehyde (MDA), carbonyl proteins, total antioxidant
      potential, total oxidant status (TOS), catalase, and glutathione-S-transferase)
      were studied using appropriate methods. RESULTS: Patients with PU showed,
      remarkably, abnormal levels of biochemical markers and relatively higher systemic
      oxidative stress compared to healthy subjects. This provides the first evidence
      that alterations in biochemical parameters and oxidative stress are features of
      PU. CONCLUSIONS: Understanding the signaling pathways involved in the development
      of PU will provide experts with additional knowledge for therapeutic strategies
      aimed at limiting the oxidative and inflammatory reactions in affected patients.
      ClinicalTrials.gov ID: NCT0257800.

PMID- 30300034
TI  - Genetic Relationship Between IL-6 rs1800796 Polymorphism and Susceptibility to
      Periodontitis.
AB  - BACKGROUND: There are accumulating reports for the potential role of Interleukin
      6 (IL-6) rs1800796 polymorphism in the risk of periodontitis. However, distinct
      conclusions are observed. In this study, we have an interest in comprehensively
      analyzing the genetic relationship between IL-6 rs1800796 and the susceptibility
      to periodontitis. METHODS: We retrieved the eligible case-control studies from on
      line database and conducted a meta-analysis. P-value of association test, OR (odd
      ratios) and 95% CI (confidence interval) were calculated for the assessment of
      potential genetic association. RESULTS: We enrolled a total of 20 case-control
      studies for pooling analysis. A positive association between periodontitis cases
      and controls was observed in the overall meta-analysis under all genetic models
      (all P < 0.05, OR > 1). Similar results were detected in the "population-based,
      PB" and "China" subgroups (all P < 0.05, OR > 1). In the "Asian" subgroup, there
      is an increased periodontitis risk under the allele, homozygote, heterozygote,
      dominant and carrier models (all P < 0.05, OR > 1). Nevertheless, negative
      results were found in the "Caucasian" subgroup under all models [all P > 0.05].
      In addition, a positive association between IL-6 rs1800796 and the risk of
      chronic periodontitis was detected under the models of allele [G vs. C], GG vs.
      CC, GG vs. CC+ CG and carrier [G vs. C] (all P < 0.05, OR > 1). CONCLUSION: IL-6
      rs1800796 may serve as one genetic risk factor for periodontitis patients in the
      Asian population, especially the Chinese population. G/G genotype of IL-6
      rs1800796 appears to be associated with an increased risk of chronic
      periodontitis.

PMID- 30300035
TI  - Critical Speed as a Measure of Aerobic Fitness for Male Rugby Union Players.
AB  - PURPOSE:: To compare critical speed (CS) derived from all-out testing (AOT) for
      linear and shuttle running with metrics from a graded exercise test (GXT), the Yo
      Yo intermittent recovery test (YYIR1), and estimation of an 800-m shuttle time
      trial. METHODS: Twelve male rugby players completed a GXT, YYIR1, a linear AOT,
      shuttle AOTs of 25- and 50-m, and an 800-m shuttle time-trial consisting of 32 x
      25-m shuttles. RESULTS:: Strong linear correlations were observed between maximum
      oxygen uptake (VO2max) and CS (m.s-1) derived from the linear AOT (3.68 +/- 0.62,
      r = 0.90, p < 0.01) and 50-m shuttle AOT (3.19 +/- 0.26, r = 0.83, p < 0.01).
      Conversely, VO2max showed lower correlations with speeds evoking CS from 25-m AOT
      (2.86 +/- 0.18, r = 0.42, p = 0.18) and YY1R1 (4.36 +/- 0.11, r = 0.55, p =
      0.07). The 800-m time trial (213.58 +/- 15.84 sec) was best predicted using
      parameters from the 25-m AOT (r = 0.93,SEE = 6.60 sec ; p < 0.001). CONCLUSION::
      The AOT is a valuable method of assessing performance-specific fitness, with CS
      from linear and 50-m shuttle AOTs being strong predictors of VO2max, rivaling
      metrics from the GXT. The YYIR1 offered limited utility compared to the AOT
      method.

PMID- 30300036
TI  - Multiple antenna placement in microwave ablation assisted by a three-dimensional
      fusion image navigation system for hepatocellular carcinoma.
AB  - PURPOSE: This study was conducted to compare a three-dimensional (3D) fusion
      image navigation system (FINS) with ultrasound (US) for guiding percutaneous
      microwave ablation (PMWA) for treatment of hepatocellular carcinoma (HCC).
      MATERIALS AND METHODS: This is a retrospective, non-randomized, comparative
      study. Our team developed a 3D FINS and used it to guide PMWAs for HCCs in 19
      patients (3D group) and compared the results to those of 24 PMWAs guided by US
      (US group). The complete ablation rate of the first session, the local tumor
      progression (LTP), intrahepatic recurrence and disease-free survival were
      compared between the groups. RESULTS: The 3D FINS was successfully applied in all
      19 patients. The mean size of HCCs was 4.14 cm +/-0.95 in 3D the group and 4.07
      cm +/-0.91 in the US group. Major complications were identified at 5.3% in the 3D
      group and 4.2% in the US group (p = .865). Average time of image fusion was
      404.53 +/- 161.84 s. There were more antenna insertions in the 3D group (3.68 +/-
      1.57) than in the US group (2.71 +/- 1.12) (p = .02). The complete ablation rate
      of the first session was higher in the 3D group (94.7%) than in the US group
      (62.5%) (p = .034). The mean follow-up period was 11.4 months +/-4.9 in the 3D
      group and 9.8 months +/-5.5 in the US group. There were no significant
      differences in technique efficacy rate and LTP rate between the two groups.
      CONCLUSIONS: The 3D FINS could be a safe, feasible and effective technique for
      guiding PMWA of HCC, which could help an operator improve the complete ablation
      rate of the first session.

PMID- 30300037
TI  - Training to Compete at Altitude: Natural Altitude or Simulated Live High: Train
      Low?
AB  - PURPOSE:: To compare the effects of natural altitude training and simulated live
      high: train low training on road race-walking performance (min), as well as
      treadmill threshold walking speed (km.h-1) at 4 mmol.L-1 (THRESH), and maximal
      oxygen consumption (VO2max), at 1380 m. METHODS:: Twenty-two elite-level, male (n
      = 15) and female (n = 7) race-walkers completed 14 days of: natural altitude
      training at 1380 m (NAT; n = 7); simulated live high; train low at 3000: 600 m
      (SIM; n = 7); or control conditions (600 m altitude; CON, n = 8). All pre and
      post-intervention testing was conducted at 1380 m, and consisted of an
      incremental treadmill test, completed prior to a 5 x 2 km road race-walking
      performance test. Differences between groups were analysed via mixed-model ANOVA
      and magnitude-based inferences, with a substantial change detected with >75%
      likelihood of exceeding the smallest worthwhile change. RESULTS:: The improvement
      in total performance time for the 5 x 2 km test in NAT was not substantially
      different to SIM, but was substantially greater (85% likely) than CON. The
      improvement in percentage decrement within the 5 x 2 km performance test in NAT
      was greater than in both SIM (93% likely) and CON (93% likely). The increase in
      VO2max was substantially greater (91% likely) in NAT than SIM. Improvement in
      THRESH was substantially greater than CON for both SIM (91% likely) and NAT (90%
      likely). CONCLUSIONS:: Both NAT and SIM may allow athletes to achieve reasonable
      acclimation prior to competition at low altitude.

PMID- 30300038
TI  - Training Load, Salivary Immunoglobulin A and Illness Incidence in Elite
      Paratriathletes.
AB  - PURPOSE:: To gain an exploratory insight into the relationship between training
      load (TL), salivary secretory immunoglobulin A (sIgA) and upper respiratory tract
      illness (URI) in elite paratriathletes. METHODS:: Seven paratriathletes were
      recruited. Athletes provided weekly saliva samples for the measurement of sIgA
      over 23 consecutive weeks (February - July) and a further 11 consecutive weeks
      (November - January). sIgA was compared to individuals' weekly training duration,
      external TL and internal TL, utilising time spent in pre-determined heart rate
      zones. Correlations were assessed via regression analyses. URI was quantified via
      weekly self-report symptom questionnaire. RESULTS:: There was a significant
      negative relationship between athletes' individual weekly training duration and
      sIgA secretion rate (p = 0.028) with changes in training duration accounting for
      12.7% of the variance (quartiles: 0.2%, 19.2%). There was, however, no
      significant relationship between external or internal TL and sIgA parameters (p
      >= 0.104). There was no significant difference in sIgA when URI was present or
      not (101% vs 118% healthy median concentration; p >= 0.225); likewise, there was
      no difference in sIgA when URI occurred within two weeks of sampling or not (83%
      vs 125% healthy median concentration; p >= 0.120). CONCLUSIONS:: Paratriathletes'
      weekly training duration significantly affects sIgA secretion rate, yet we did
      not find a relationship between external or internal TL and sIgA parameters.
      Further, it was not possible to detect any link between sIgA and URI occurrence
      which throws into question the potential of using sIgA as a monitoring tool for
      early detection of illness.

PMID- 30300039
TI  - Quantitative dynamic contrast-enhanced ultrasound may help predict the outcome of
      hepatocellular carcinoma after microwave ablation.
AB  - PURPOSE: Previous studies have reported that parameters of dynamic contrast
      enhanced ultrasound (DCE-US) could predict prognosis of hepatocellular carcinoma
      (HCC) patients after antiangiogenic therapies. In this study, we aimed to
      investigate the correlation of DCE-US parameters and the prognosis of HCC
      patients after microwave ablation (MWA). MATERIALS AND METHODS: Between June 2012
      and January 2018, a total of 35 HCC patients who received MWA with a curative
      intent were enrolled. Pre-ablation DCE-US, liver biopsy, CD34 staining, and
      vascular endothelial growth factor (VEGF) staining were performed. DCE-US
      parameters were extracted from time-intensity curves using SonoLiver software.
      The correlation of DCE-US parameters with histopathology results and overall
      survival (OS) were investigated. RESULTS: Quantitative analysis showed that IMAX,
      RT, TTP, and mTT of HCC were statistically different with that of reference liver
      parenchyma (all p < .001). Microvessel density was shown to be positively
      correlated with IMAX and negatively correlated with TTP (r = 0.755 and -0.647,
      both p < .01). Additionally, positive correlations were observed between IMAX and
      VEGF expression (r = 0.665, p < .01). After a median follow-up of 22 months
      (range 6-64 months), local recurrence was detected in three patients. Largest
      diameter and TTP were shown to help predict OS in univariate and multivariate
      analyses. CONCLUSION: DCE-US parameter may help predict the outcome of HCC
      patients after MWA, though further study is still needed.

PMID- 30300040
TI  - Advances and challenges in recombinant Mycobacterium bovis BCG-based HIV vaccine
      development: lessons learned.
AB  - INTRODUCTION: Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome,
      tuberculosis, and malaria are responsible for most human deaths produced by
      infectious diseases worldwide. Vaccination against HIV requires generation of
      memory T cells and neutralizing antibodies, mucosal immunity, and stimulation of
      an innate immune responses. In this context, the use of Mycobacterium bovis
      bacillus Calmette-Guerin (BCG) as a live vaccine vehicle is a promising approach
      for T-cell induction. Areas covered: In this review, we provide a comprehensive
      summary of the literature regarding immunogenicity studies in animal models
      performed since 2005. Furthermore, we provide expert commentary and 5-year view
      on how the development of potential recombinant BCG-based HIV vaccines involves
      careful selection of the HIV antigen, expression vectors, promoters, BCG strain,
      preclinical animal models, influence of preexisting immunity, and safety issues,
      for the rational design of recombinant BCG:HIV vaccines to prevent HIV
      transmission in the general population. Expert commentary: The three critical
      issues to be considered when developing a rBCG:HIV vaccine are codon
      optimization, antigen localization, and plasmid stability in vivo. The use of
      integrative expression vectors are likely to improve the mycobacterial vaccine
      stability and immunogenicity to develop not only recombinant BCG-based vaccines
      expressing second generation of HIV-1 immunogens but also other major pediatric
      pathogens to prime protective responses shortly following birth.

PMID- 30300041
TI  - Poxvirus-based vector systems and the potential for multi-valent and multi
      pathogen vaccines.
AB  - INTRODUCTION: With the increasing number of vaccines and vaccine-preventable
      diseases, the pressure to generate multi-valent and multi-pathogen vaccines
      grows. Combining individual established vaccines to generate single-shot
      formulations represents an established path, with significant ensuing public
      health and cost benefits. Poxvirus-based vector systems have the capacity for
      large recombinant payloads and have been widely used as platforms for the
      development of recombinant vaccines encoding multiple antigens, with considerable
      clinical trials activity and a number of registered and licensed products. Areas
      covered: Herein we discuss design strategies, production processes, safety
      issues, regulatory hurdles and clinical trial activities, as well as pertinent
      new technologies such as systems vaccinology and needle-free delivery. Literature
      searches used PubMed, Google Scholar and clinical trials registries, with a focus
      on the recombinant vaccinia-based systems, Modified Vaccinia Ankara and the
      recently developed Sementis Copenhagen Vector. Expert commentary: Vaccinia-based
      platforms show considerable promise for the development of multi-valent and multi
      pathogen vaccines, especially with recent developments in vector technologies and
      manufacturing processes. New methodologies for defining immune correlates and
      human challenge models may also facilitate bringing such vaccines to market.

PMID- 30300042
TI  - Upfront HIPEC and bevacizumab-containing adjuvant chemotherapy in advanced
      epithelial ovarian cancer.
AB  - INTRODUCTION: In advanced epithelial ovarian cancer patients, the standard of
      care is primary debulking surgery, followed by first-line chemotherapy often with
      bevacizumab addiction. In this context, some experiences have shown that a
      comprehensive treatment approach to surgery combined with hyperthermic
      intraperitoneal chemotherapy (HIPEC) could improve the prognosis. OBJECTIVE: This
      is a study aimed to explore the feasibility of primary debulking surgery and
      HIPEC upfront followed by first-line therapy with bevacizumab. STUDY DESIGN:
      Phase II monocentric, open label, non-randomised and single-arm study. Forty
      patients affected by advanced ovarian cancer submitted to primary debulking
      surgery with HIPEC were enrolled in the study. After surgery, all patients
      underwent systemic chemotherapy with bevacizumab addiction. RESULTS: Complete
      cytoreduction (RT = 0) was achieved in all cases. Treatment-related early
      complications were observed in 23 patients and in 15 cases were G1-G2. Major
      complications were reported in 8 patients. No postoperative death was recorded.
      Subsequent chemotherapy was administered in all cases. Median time between
      surgery and first cycle of chemotherapy was 42 days (range 30-76). Concomitant
      bevacizumab was administered in 34 patients (85%). Maintenance with bevacizumab
      was feasible in 33 patients (82.5%) and its withdrawal was necessary for 1
      patient (2.5%) due to G3 hypertension. CONCLUSION: Our data suggest that HIPEC
      can be safely introduced in the upfront therapy of advanced ovarian cancer.

PMID- 30300043
TI  - Sequential Pulse Compression's Effect on Blood Flow in the Lower Extremity.
AB  - Several interventions are available to reduce the intensity and duration of the
      unwanted effects (e.g. muscle soreness) associated with physical activity such as
      massage, compression garments, and sequential pulse compression (SPC). Such
      interventions aim to increase blood flow to alleviate symptoms. However, there is
      a lack of evidence to support the use of SPC to alter total hemoglobin
      concentration (THb) in active individuals. The aim of this study was to examine
      the acute effects of a single session of SPC on hemoglobin concentration compared
      to a control condition. Thirty-four physically active and healthy participants
      (females=12, males=22) completed the study. We randomly assigned participants to
      first receive the experimental (SPC) or control condition. Measures were recorded
      pre- and post-condition. Participants returned to the laboratory to complete the
      second condition >=24 hours after the first condition. Relative change in THb,
      oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) measures were
      recorded using near-infrared spectroscopy placed on the muscle belly of the
      medial gastrocnemius of the dominant limb. SPC significantly increased THb
      (P<0.001, d=0.505) and O2Hb (P<0.001, d=0.745) change scores compared to the
      control condition. No statistical difference in HHb change scores were found
      between SPC and control conditions, but a medium effect size suggests potential
      biological significance (p=0.055, d=0.339). Overall, SPC increases THb to the
      lower extremity, and may be a viable option in the management of muscle soreness
      related to physical activity.

PMID- 30300044
TI  - Acylated ghrelin protects aorta damage post-MI via activation of eNOS and
      inhibition of angiotensin-converting enzyme induced activation of NAD(P)H
      dependent oxidase.
AB  - NAD(P)H dependent oxidase derived-reactive oxygen species (ROS) due to activation
      of the renin-angiotensin-aldosterone system (RAAS) in blood vessels
      postmyocardial infarction MI or during the HF leads to endothelium dysfunction
      and enhanced apoptosis. Acylated ghrelin (AG) is a well-reported cardioprotective
      and antiapoptotic agent for the heart. AG receptors are widely distributed in
      most of blood vessels, suggesting a role in the regulation of endothelial
      function and survival. This study investigated if AG can protect aorta of rats'
      postmyocardial infarction (MI)-induced damage and endothelial dysfunction. Adult
      male rats were divided into four groups of (1) Sham, (2) Sham + AG, (3) MI, and
      (4) MI + AG. Vehicle (normal saline) or AG (100 u/kg) was administered to rats
      for 21 consecutive days, after which, numerous biochemical markers were detected
      by blot. Both histological and electron microscope studies were carried on aortic
      samples from MI-induced rats. AG increased protein levels of both total and
      phosphorylated forms of endothelial nitric oxide synthase (eNOS and p-eNOS,
      respectively). Only in MI-treated rats, AG prevented the decreases in the levels
      of reduced glutathione (GSH) and superoxide dismutase (SOD) and lowered levels of
      malondialdehyde (MDA) and glutathione disulfide (GSSG). Concomitantly, it lowered
      the increased protein levels of angiotensin-converting enzyme (ACE), p22phox and
      cleaved caspase-3 and prevented the aorta histological and ultrustructural
      abnormalities induced by MI.

PMID- 30300045
TI  - How and Why School Is Important to Teenagers with Cancer: Outcomes from a Photo
      Elicitation Study.
AB  - BACKGROUND: Being diagnosed with cancer during the teenage years can be
      significant given that young people are at a key developmental, educational, and
      future-planning stage. Little is known about young people's attitude toward and
      engagement with school postdiagnosis, nor how this changes over time. We adopted
      a novel qualitative approach to examine accounts over time of young people
      recently diagnosed with cancer. METHODS: Twelve teenagers (13-16 years), recently
      diagnosed with cancer, participated in photo-elicitation interviews at three time
      points (~2, 6, and 9 months postdiagnosis), generating 30 interviews in total.
      Photo-elicitation interviews center around images that participants bring to
      represent key experiences and issues that matter to them. Transcripts were
      analyzed using interpretative phenomenological analysis. RESULTS: Seven themes
      were generated, representing experiences over time. Themes convey how significant
      school was to the young people postdiagnosis, principally because it mattered to
      them to maintain a normative educational pathway. Young people felt tension
      between wanting to be the same as their peers but feeling distinctly changed.
      Keeping ownership and control of their cancer story within school was
      challenging. Survivorship brought, for some, a legacy of missed schooling.
      CONCLUSION: Support for young people and reintegration plans for school need to
      be tailored to the young person's emerging way of understanding their cancer and
      recovery, and their orientation to coping. Young people need help to understand
      that schoolwork exemptions/extensions do not implicate academic deficiency, and
      how they could accept a "same but different" position as they continue to develop
      personally and educationally with their peers.

PMID- 30300046
TI  - The efficacy of lower limb screening tests in predicting PlayerLoad within a
      professional soccer academy.
AB  - CONTEXT:: Training exposure has been associated with injury epidemiology in elite
      youth soccer, where lower limb musculoskeletal screening is commonly used to
      highlight injury risk. However, there has been little consideration of the
      relationship between lower limb screening and the loading response to soccer
      activities. OBJECTIVE:: To quantify the efficacy of using screening tests to
      predict the loading elicited in soccer-specific activities, and to develop a
      hierarchical ordering of musculoskeletal screening tests to identify test
      redundancy and inform practice. DESIGN:: Correlational. SETTING:: Professional
      soccer club academy. PARTICIPANTS:: 21 elite male soccer players aged 15.7 +/-
      0.9 years. INTERVENTION:: Players completed a battery of five screening tests
      (knee to wall, hip internal rotation, adductor squeeze, single leg hop, anterior
      reach), and a 25min standardised soccer session with a GPS unit placed at C7 to
      collect multi-planar PlayerLoad data. MAIN OUTCOME MEASURES:: Baseline data on
      each screening test, along with uni-axial PlayerLoad in the medio-lateral,
      anterio-posterior and vertical planes. RESULTS:: Stepwise hierarchical modelling
      of the screening tests revealed that dominant leg knee to wall distance was the
      most prevalent and powerful predictor of multi-planar PlayerLoad, accounting for
      up to 42% of variation in uni-axial loading. The adductor squeeze test was the
      least powerful predictor of PlayerLoad. Of note, one player who incurred a knee
      injury within three weeks of testing had shown a 20% reduction in knee to wall
      distance compared with peers, and elicited 23% greater PlayerLoad, supporting the
      hierarchical model. CONCLUSIONS:: There was some evidence of redundancy in the
      screening battery, with implications for clinical choice. Hierarchical ordering
      and a concurrent case study highlight dominant leg knee to wall distance as the
      primary predictor of multi-axial loading in soccer. This has implications for the
      design and interpretation of screening data in elite youth soccer.

PMID- 30300047
TI  - Low Doses of Caffeine: Enhancement of Physical Performance in Elite Adolescent
      Male Soccer Players.
AB  - CONTEXT:: Large doses of ~6 mg.kg-1 body mass have improved performance during
      intermittent running, jumping, and agility protocols. However, there are sparse
      data on low doses of caffeine, especially in elite adolescent soccer players.
      METHOD:: Fifteen elite youth soccer players (177.3+/-4.8 cm, 66.9+/-7.9 kg and
      16+/-1 y) participated in the study, consuming 1, 2, or 3 mg.kg-1 caffeine in a
      gelatin capsule or a 2-mg.kg-1 placebo in a single-blind, randomized, crossover
      study design. Testing consisted of a 20-m sprint, arrowhead agility (change of
      direction [CoD] right or left), countermovement jump (CMJ), and Yo-Yo
      Intermittent Recovery Test Level-1 (Yo-Yo IR1). Post-exercise CMJ performance was
      assessed as participants exited the Yo-Yo IR1. Data were analyzed using a
      Bayesian multilevel regression model to provide explained variance and
      probabilities of improvement (p=%). RESULTS:: 3 mg.kg-1 caffeine presented the
      highest probabilities of change compared with placebo across a range of tests
      (mean +/- SD, p= %). Times for 20-m sprint were 3.15+/-0.10s vs 3.18+/-0.09s
      (p=73%), CoD-R times were 8.43+/-0.24s vs 8.55+/-0.25s (p=99%), CoD-L times were
      8.44+/-0.22s vs 8.52+/-0.18s (p=85%), Yo-Yo IR1 distance was 2440+/-531m vs
      2308+/-540m (p=15%), and preexercise CMJ height was 41.6+/-7.2cm vs 38+/-8.5cm
      (p=96%). Postexercise CMJ was higher with 3 mg.kg-1 than with placebo (42.3+/-8cm
      vs 36.6+/-8cm [p=100%]). Doses of 1 or 2 mg.kg-1 caffeine also demonstrated the
      ability to enhance performance but were task dependent. CONCLUSION:: Low doses of
      caffeine improve performance but are dose and task dependent. A dose of 3 mg.kg-1
      caffeine improved performance across the majority of tests with potential to
      further improve postexercise CMJ height.

PMID- 30300048
TI  - The Effect of Body Checking Policy Changes on Concussion Incidence in Canadian
      Male Youth Ice Hockey Players: A Critically Appraised Topic.
AB  - CLINICAL SCENARIO:: Current studies have identified body checking as the most
      common cause of sports-related concussion in ice hockey across all divisions and
      levels. As a result, many hockey organizations, particularly in youth sports,
      have implemented rules making body checking to the head, face, and/or neck,
      illegal. Such a rule, in Canada, makes age 13 the first age in which individuals
      can engage in body-checking. Despite these changes, effectiveness of their
      implementation on the incidence of concussion in Canadian male youth ice hockey
      players remains unclear. CLINICAL QUESTION:: What is the effect of body checking
      policy changes on concussion incidence in male youth ice hockey players? SUMMARY
      OF KEY FINDINGS:: Two out of the three included studies reported a decrease in
      the incidence of concussion once a body checking policy change was implemented.
      The third study showed an increase; however, it is important to note that this
      may be due, in part, to increased awareness leading to better reporting of
      injuries. CLINICAL BOTTOM LINE:: Current evidence supports a relationship between
      body checking policy implementation and decreased concussion incidence; however,
      more research is needed to understand the long-term implications of policy change
      and the effects in other leagues. In addition, further data are needed to
      differentiate between increased concussion incidence resulting from concussion
      education efforts that may improve disclosure and increased concussion incidence
      as a direct result of policy changes. STRENGTH OF RECOMMENDATION:: Grade B
      evidence exists that policy changes regarding body checking decreases concussion
      incidence in youth, male ice hockey players.

PMID- 30300049
TI  - The Experience and Meaning of Physical Activity in Assisted Living Facility
      Residents.
AB  - Assisted living (AL) residents engage in very low levels of physical activity
      (PA) placing them at increased risk for mobility disability and frailty. But many
      residents in AL may not perceive the need to increase their PA. This study
      explored the experience, meaning and perceptions of PA in 20 older adults in
      assisted living. Factors associated with PA were also examined. Qualitative data
      were collected using semi-structured interviews and analyzed using Colaizzi's
      (1978) phenomenological methodology. Six themes were identified: PA was
      experienced as planned exercise, activities of daily living, and social
      activities based on a schedule or routine; PA meant independence and confidence
      in the future; residents perceived themselves as being physically active; social
      comparisons influenced perception of PA; personal health influenced PA;
      motivations and preferences influenced PA. Findings highlight the importance of
      residents' personal perceptions of PA and effects of the social milieu in the
      congregate setting on PA.

PMID- 30300050
TI  - Three-Dimensional Kinematics and Power Output in Elite Para-Kayakers and Elite
      Able-Bodied Flat-Water Kayakers.
AB  - Trunk, pelvis and leg movement are important for performance in sprint kayaking.
      Para-kayaking is a new Paralympic sport in which athletes with trunk and/or leg
      impairment compete in three classification groups. The purpose of this study was
      to identify how physical impairments impact on performance by examining:
      differences in three-dimensional joint range of motion (RoM) between 10 (4
      females, 6 males) elite able-bodied kayakers and 41 (13 females, 28 males) elite
      para-kayakersfrom the three classification groups, and which joint angles were
      correlated with power output during high intensity kayak ergometer paddling.
      There were significant differences in RoM between the able-bodied kayakers and
      the three para-kayak groups for the shoulders (flexion, rotation: able-bodied
      kayakers<para-kayakers), trunk and pelvis (rotation: able-bodied kayakers>para
      kayakers) and legs (hip, knee, ankle flexion: able-bodied kayakers>para-kayakers)
      during paddling. Furthermore, athletes with greater impairment exhibited lower
      trunk and leg RoM compared to those with less impairment. Significant positive
      correlations were observed for both males and females between power output and
      peak shoulder and trunk flexion, trunk and pelvis rotation RoM and hip, knee and
      ankle flexion RoM. This information is important for understanding how key
      kinematic and kinetic variables for para-kayaking performance vary between
      athletes from different classification groups.

PMID- 30300051
TI  - Females Demonstrate Reduced Vertical Ground Reaction Forces following a 4-week
      Jump-Landing Feedback Intervention without Negatively Affecting Vertical Jump
      Performance University of Toledo, Musculoskeletal Health and Movement Science
      Laboratory.
AB  - CONTEXT:: High vertical ground reaction force (vGRF) when initiating ground
      contact during jump-landing is one biomechanical factor that may increase risk of
      anterior cruciate ligament injury. Intervention programs have been developed to
      decrease vGRF to reduce injury risk, yet generating high forces is still critical
      for performing dynamic activities such as a vertical jump task. OBJECTIVE:: To
      evaluate if a jump-landing feedback intervention, cueing a decrease in vGRF,
      would impair vertical jump performance in a separate task (Vertmax). DESIGN::
      Randomized controlled trial. PATIENTS (OR OTHER PARTICIPANTS):: Forty-eight
      recreationally-active females (feedback: n=31, 19.63+/-1.54 years, 1.63+/-0.08cm,
      58.13+/-7.84kg; control: n=15, 19.6+/-1.68 years, 1.64+/-0.05cm, 60.11+/-8.36kg)
      participated in this study. INTERVENTION:: Peak vGRF during a jump-landing and
      Vertmax were recorded at baseline and 4-weeks post. The feedback group
      participated in 12 sessions over the 4-week period consisting of feedback
      provided for 6 sets of 6 jumps off a 30cm box. The control group was instructed
      to return to the lab 28 days following the baseline measurements. MAIN OUTCOME
      MEASURES:: Change scores (post-baseline) were calculated for peak vGRF and
      Vertmax. Group differences were evaluated for peak vGRF and Vertmax using a Mann
      Whitney U test (P<0.05). RESULTS:: There were no significant differences between
      groups at baseline (p>0.05). The feedback group (-0.5+/-0.3N/kg) demonstrated a
      greater decrease in vGRF compared to the control group (0.01+/-0.3N/kg) (t(46)=
      5.52, p<0.001). There were no significant differences in change in Vertmax
      between groups (feedback=0.9+/-2.2cm, Control=0.06+/-2.1cm; t(46)=0.46, p=0.643).
      CONCLUSIONS:: While the feedback intervention was effective in decreasing vGRF
      when landing from a jump, these participants did not demonstrate changes in
      vertical jump performance when assessed during a different task. Practitioners
      should consider implementing feedback intervention programs to reduce peak vGRF,
      without worry of diminished vertical jump performance.

PMID- 30300052
TI  - Protective Effects of beta-Carotene Against Ammonium Sulfate Toxicity:
      Biochemical and Histopathological Approach in Mice Model.
AB  - In this study, the protective role of beta-carotene against ammonium sulfate
      induced toxicity has been evaluated in Mus musculus var. albino mice, along with
      biochemical and histopathological parameters. Some biochemical parameters such as
      aspartate transaminase (AST), alanine transaminase (ALT), blood urea nitrogen
      (BUN), creatinine and oxidative stress parameters, malondialdehyde (MDA), and
      glutathione (GSH) levels in kidney and liver tissues were investigated. The mice
      were randomly divided into six groups. Group I received intraperitoneal
      injections of 0.9% NaCl; group II received orally administered 250 mg kg-1 bw
      beta-carotene, group III received orally administered 500 mg kg-1 bw beta
      carotene; group IV received 320 mg kg-1 bw ammonium sulfate; group V was given
      250 mg kg-1 bw beta-carotene +320 mg kg-1 of bw ammonium sulfate; and group VI
      received orally administered 500 mg kg-1 of bw beta-carotene +320 mg kg-1 of bw
      ammonium sulfate. As a result, it was determined that the ammonium sulfate
      treatment causes significant changes in the biochemical and oxidative stress
      parameters and also in histological examinations. In group IV, significant
      increases in ALT, AST, BUN, MDA, and creatinine levels, and a significant
      decrease in GSH levels were observed compared with control group. In
      histopathological examinations, different pathological findings such as
      proteinaceous deposits, thickening of basement membrane, hyaline cast in kidney
      tissue and stellate cell, karyomegaly, and binucleated cells in liver tissue were
      observed. beta-carotene treatment in group V and VI ameliorated the elevated
      levels of liver enzymes and improved oxidative stress and histopathological
      findings, and so, it could be concluded that beta-carotene offered remarkable
      protection against ammonium sulfate-induced toxicity.

PMID- 30300053
TI  - Suboptimal Use of Effective Contraceptive Methods in Young Mexican Women With
      Breast Cancer.
AB  - PURPOSE: Contraceptive counseling and adherence in young women with breast cancer
      (BC) is a relevant issue because chemotherapy and hormonal treatment resulting in
      amenorrhea do not preclude unintended pregnancies. Currently, there is limited
      evidence from high-income countries; however, there are no studies regarding use
      of contraceptives in patients with BC in Mexico. This study aimed to determine
      the rate of contraceptive use in young Mexican women with BC during cancer
      treatment, characterize their contraceptive preferences, and assess contraceptive
      counseling by Mexican physicians. PATIENTS AND METHODS: A cross-sectional survey
      was conducted regarding contraceptive use and counseling among women age 40 years
      or younger at BC diagnosis who had completed chemotherapy in the previous 5 years
      or who were currently receiving long-term treatment with hormonal therapy and/or
      trastuzumab at a large tertiary health care facility in Mexico. RESULTS: Of a
      total of 104 eligible women with median age at diagnosis of 34 years, 51.1%
      reported using a contraceptive during chemotherapy and 45.7% reported using a
      contraceptive during other types of cancer treatment (hormonal therapy and
      trastuzumab). Of the 51 patients (49%) who were sexually active during
      chemotherapy, 76.5% used contraception, but only 29.4% used an effective
      contraceptive method. When asked about contraceptive counseling, only 16.7%
      recalled being advised by their health care provider. Sexually active women who
      received contraceptive counseling used contraceptives more often than women who
      were not counseled (83.3% v 22.2%). CONCLUSION: A minority of young women with BC
      in Mexico use effective contraception methods during cancer treatment and receive
      contraceptive counseling. Informing all premenopausal patients with BC about
      effective use of contraception methods during treatment should be an essential
      aspect of the supportive care of young women.

PMID- 30300054
TI  - Blood Flow Restriction Therapy Versus Standard Care for Reducing Quadriceps
      Atrophy After Anterior Cruciate Ligament Reconstruction.

PMID- 30300055
TI  - Hip abductor and adductor muscles activity patterns during landing after anterior
      cruciate ligament injury.
AB  - CONTEXT:: Hamstring and quadriceps activity adaptations are well known in
      individuals with anterior cruciate ligament deficiency (ACLD) and reconstructed
      (ACLR) to potentially compensate for knee joint instability. However, few studies
      have explored hip muscles activity patterns after ACL injury. OBJECTIVE:: to
      examine the activation characteristics of gluteus medius (GMED) and adductor
      longus (AL) in ACLR and ACLD subjects compared to controls. DESIGN:: case-control
      study. SETTING:: Athletic training room and university lab. PARTICIPANTS:: 12
      healthy and 24 ACL injured (12 ACL reconstructed and 12 ACL deficit)
      recreationally active male volunteers. INTERVENTIONS:: Surface EMG of the GMED
      and AL were recorded during a single leg vertical drop landing and normalized to
      maximum voluntary isometric contractions (MVICs). MAIN OUTCOME MEASURES::
      Preparatory and reactive muscle activity and co-activation were analyzed from 100
      milliseconds prior to initial contact to 250 milliseconds post-contact. RESULTS::
      During reactive activity, ACL injured (ACLR and ACLD) participants demonstrated
      significantly lower peak GMED activity compared to controls (F=4.33, P=0.021). In
      addition, ACLR participants exhibited significantly lower reactive GMED:AL co
      activiation muscle activity compared to controls (F=4.09, P= 0.026). CONCLUSION::
      Our findings suggest neuromuscular adaptations of the hip musculature are present
      in people at least two years from ACL injury. GMED activation exercises should be
      considered in designing rehabilitation programs for ACL injured individuals.

PMID- 30300056
TI  - PHYSICAL EXERCISE FOR INDIVIDUALS WITH SPINAL CORD INJURY: SYSTEMATIC REVIEW
      BASED ON THE INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY, AND HEALTH.
AB  - INTRODUCTION:: Considering the reduction of physical activity performed daily in
      people with spinal cord injury, it is necessary to analyze the interventions
      based on physical exercises in order to provide recommendations based on
      evidence. OBJECTIVES:: To review and evaluate the literature on physical exercise
      interventions for individuals with SCI, based on the ICF, as well as
      physiological parameters for exercise prescription. METHOD:: A systematic review
      of the literature produced from August 2016 to February 2017 within the PubMed,
      EMBASE, Cochrane Library, and MEDLINE databases. Results: Two independent
      examiners conducted a search in which 223 articles were initially found. A third
      evaluator verified possible divergences and generated a final list of 25 articles
      that strictly met the inclusion criteria, 5 of which investigated the effects of
      aerobic exercise, 2 of resistance training, 2 of balance training, 12 of gait
      training, and 4 evaluating the combined effect of two or more forms of training.
      CONCLUSION:: Considering studies classified as high and moderate quality of
      evidence, positive effects were observed in the domains of structures and
      functions, in aerobic, resistance training and combined exercises, and in some
      studies with gait training. In the domain of activities and participation,
      positive effects were observed in the studies with gait training, balance
      training, and combined interventions.

PMID- 30300057
TI  - Comparing Anterior Cruciate Ligament Injury Risk Variables Between Unanticipated
      Cutting and Decelerating Tasks.
AB  - The purpose of this study was to examine the relationship between ACL injury risk
      factors in unanticipated cutting and decelerating. Three-dimensional kinematics
      and ground reaction forces were collected on eleven females (22+/-2yrs, 1.67+/
      0.08m, 68.5+/-9.8kg) during two unanticipated tasks. Paired samples t-tests were
      performed to compare dependent variables between tasks. Spearman rank correlation
      coefficients were calculated to analyze the relationship between peak internal
      knee adduction moment and peak anterior tibial shear force during two
      unanticipated tasks. Significantly greater knee abduction angles, peak knee
      adduction moments, and peak anterior tibial shear forces were observed during
      cutting (p<=0.05). A strong positive correlation existed between decelerating
      anterior tibial shear force and cutting anterior tibial shear force (rho=0.67),
      while correlations between decelerating knee adduction moment and cutting knee
      adduction moment and decelerating anterior tibial shear force and cutting knee
      adduction moment were not significant. In situations where time management is a
      necessity, and only one task can be evaluated, it may be more appropriate to
      utilize an unanticipated cutting task rather than an unanticipated deceleration
      task because of the increased knee adduction moment and anterior tibial shear
      force. These data can help future clinicians in better designing more effective
      ACL injury risk screening methods.

PMID- 30300058
TI  - Use of Physical Activity Questionnaires in People With Dementia: A Scoping
      Review.
AB  - Physical activity questionnaires are an important means to assess habitual
      physical activity. It remains unclear what questionnaires are used and whether
      they are appropriate for people with dementia who have impaired information
      recall but are also often largely sedentary. This scoping review aimed to
      identify and quantify the use of physical activity questionnaires within a
      dementia population. Eighteen studies met the inclusion criteria for this review.
      The majority of studies used questionnaires that were validated for use within an
      older adult population (e.g., Modified Baecke Questionnaire for the Elderly),
      though none had specifically been validated for use in people with dementia.
      Interestingly, just over half of studies (N= 10, 55.6%) adapted the
      questionnaires from the original validated version by allowing a proxy to provide
      input into the responses. Future research needs to robustly validate the use of
      proxy-report measures of physical activity in people with dementia.

PMID- 30300059
TI  - Recent ankle injury, sport participation level and tests of proprioception.
AB  - OBJECTIVE:: Assessing the effects of ankle injury and sport participation level
      on ankle proprioceptive sensitivity using a joint position reproduction (JPR)
      test and an inversion movement extent discrimination test. DESIGN:: Cross
      sectional. SETTING:: Biomechanics lab. PARTICIPANTS:: 45 student athletes aged 21
      to 30 years (M 24.8 years). MAIN OUTCOME MEASURES:: Participants were tested for
      ankle inversion sensitivity using two devices; movement reproduction error was
      obtained from JPR in non-weight-bearing (N-WB) at 10 and 15 degrees of inversion,
      and an ankle proprioceptive sensitivity score was obtained from the active
      movement extent discrimination apparatus (AMEDA), representing ability to
      differentiate five inversion movement extents between 10.5 degrees  and 14.5
      degrees , with testing in both N-WB and WB. RESULTS:: For the 34 athletes with no
      ankle injury in the previous 12 months, the sensitivity scores achieved on the
      AMEDA were significantly higher (p < 0.01) than for the 11 athletes with ankle
      injury, and this injury effect was significantly greater in WB (p=0.013). In JPR
      testing, the 2.96 degrees  error of reproduction for athletes with no recent
      ankle injury was not significantly different from the 3.36 degrees  error for
      those with ankle injury (p=0.46). Correlation of current sport participation
      level with JPR showed less error for higher level performers (r = 0.49, p =
      0.001), but no significant relationship to WB or N-WB AMEDA scores (both p >
      0.61). WB AMEDA scores were significantly higher for athletes who had competed at
      a higher level of sport competition when aged <18 years (r = - 0.57, p < 0.001).
      CONCLUSIONS:: Previous ankle sprains affected proprioceptive scores on the WB
      AMEDA and N-WB AMEDA tests, indicating the sensitivity of the AMEDA movement
      discrimination test to the effects of ankle injury. The correlation between JPR
      scores and current level of sport participation suggests sensitivity of the JPR
      test to current ankle use.

PMID- 30300060
TI  - The Acute Effects of Mat Pilates on Hemodynamic and Salivary Nitrate Responses
      After Exercise in Postmenopausal Women.
AB  - The aim of study was to compare the hemodynamic and salivary responses after Mat
      Pilates, aerobic, resistance exercise and control. 16 normotensive postmenopausal
      women performed: PILATES:ten floor exercises; AEROBIC:35 minutes on the treadmill
      (60 to 70%of heart rate reserve); RESISTANCE: 60% of 1RM; CONTROL:no physical
      exercise. Blood pressure (BP) and heart rate variability (HRV) were evaluated at
      rest and 60 minutes after the intervention. Saliva samples were collected at
      rest, immediately, 30' and 60' after exercise for analysis of nitrite
      concentration (NO2-) and total proteins (TP). SBP, DBP and MBP AUC were lower
      (p<0.05) after both aerobic and resistance exercises sessions, but not the
      Pilates session, when compared with the control session. The NO2- concentrations
      in saliva were higher 60' after the end of all exercise sessions, The HRV was
      higher after the resistance exercise. Aerobic and resistance exercises were
      capable of decreasing arterial blood pressure after acute exercise.

PMID- 30300061
TI  - TV Viewing is Associated With All-Cause Mortality in Older Adults With
      Hypertension: Findings From a 6-Year Longitudinal Study.
AB  - The purpose of this study was to examine the longitudinal association between TV
      viewing and all-cause mortality in older adults with hypertension. Sedentary
      behavior, physical activity, hypertension and other chronic diseases were
      assessed by face-to-face interviews and confirmed by medical history. Mortality
      was reported by relatives and confirmed in medical records of the National Health
      System. The fully- adjusted model showed a direct association between high TV
      viewing time and all-cause mortality (HR: 1.65 [95% CI 1.02 - 2.68]). Women with
      high TV viewing were more likely to die than men. Higher TV viewing time was
      associated with all-cause mortality among those with diabetes and hypertension
      (HR: 3.54 [95% CI 1.64 - 7.66]). The findings from this longitudinal study show
      that higher TV viewing time is associated with higher risk for all-cause
      mortality among older adults with hypertension, independently of physical
      activity and other potential confounders.

PMID- 30300062
TI  - Atorvastatin induces autophagy in MDA-MB-231 breast cancer cells.
AB  - This article explores the effects of atorvastatin on cultured breast cancer
      cells. Our experiment demonstrated that atorvastatin triggered autophagy and
      inhibited proliferation in breast cancer cells. A CCK8 assay indicated that
      atorvastatin can inhibit the activity of MDA-MB-231 breast cancer cells. Western
      blotting results showed that atorvastatin increased the conversion of light chain
      3 (LC3)-I to LC3-phosphatidylethanolamine conjugate (LC3-II). Confocal microscopy
      was used to reveal the appearance of a punctate structure in the cytoplasm, and
      electron microscopy was used to reveal the formation of double-membrane
      autophagosome. In conclusion, our study showed that atorvastatin may affect MDA
      MB-231 breast cancer cells by inducing autophagy.

PMID- 30300063
TI  - Clinical Breathing Mechanics Differ Based on Test and Position.
AB  - CONTEXT:: Altered diaphragm function is linked to decreased core stabilization,
      postural changes, and decreased function. Two clinical tests used to assess
      breathing are the hi-lo and lateral rib expansion (LRE) tests. It is currently
      unknown how breathing classification based on these tests differ, and how their
      results are affected by varying test positions. OBJECTIVE:: To compare results of
      breathing tests when conducted in varying test positions. DESIGN:: Prospective
      cross-sectional study. SETTING:: University laboratory. PARTICIPANTS:: 50 healthy
      adults (female=31, male=29; age=29.3+/-4.1 years; height=170.0+/-10.4cm;
      weight=70.7+/-15.1kg). INTERVENTION(S):: Hi-lo and LRE tests in supine, seated,
      standing, and half-kneeling body positions. All tests were recorded and later
      scored by a single examiner. A generalized estimating equations approach with
      breathing test and body position as factors was used for analysis. Pairwise
      comparison with Bonferroni correction was used to adjust for multiple tests.
      Statistical significance was set at p=.05, 2-tailed. MAIN OUTCOME MEASURES:: Hi
      lo and LRE tests were scored based on the presence or absence of abdominal
      excursion, lateral rib expansion, and superior rib cage migration. Following
      scoring, results were classified as functional or dysfunctional based on
      observation of these criteria. RESULTS:: A significant breathing test x test
      position interaction (P<0.001) was noted, as well as main effects for test
      (P<0.001) and test position (P<0.001).. All hi-lo test positions identified
      significantly more dysfunctional breathers in positions of increased stability
      demand (P<0.001-0.006), except between standing and half-kneeling positions
      (P=0.52). In the LRE test, all positions were similar (P=1.000) except for half
      kneeling, which was significantly different from all other positions (P<0.001).
      CONCLUSIONS:: The hi-lo test and LRE tests assess different breathing mechanics.
      Clinicians should use these tests in combination to gain a comprehensive
      understanding of a person's breathing pattern. The hi-lo test should be
      administered in multiple testing positions.

PMID- 30300064
TI  - Validity of the Open Barbell and Tendo Weightlifting Analyzer Systems Versus the
      Optotrak Certus 3D Motion Capture System for Barbell Velocity.
AB  - PURPOSE:: The aim of this study was to examine the validity of two linear
      position transducers, the Tendo Weightlifting Analyzer System (TWAS) and Open
      Barbell System (OBS), compared to a criterion device, the Optotrak Certus Three
      Dimensional Motion Capture System (OC3D). METHODS:: Twenty-five males (age: 25+/
      3yrs, height: 174.0+/-6.7cm, body mass: 89.0+/-14.7kg, squat one-repetition
      maximum-1RM: 175.8+/-34.7kg) with >=2yrs of resistance training experience
      completed a back 1RM and one set to failure at 70% of 1RM. Average (ACV) and peak
      (PCV) concentric velocity were recorded by all three devices during the final
      warm-up set, all 1RM attempts, and every repetition during the 70% set. RESULTS::
      In total, 575 samples were obtained. Bland-Altman plots, Mountain plots, a one
      way ANOVA, standard error of measurement, and intraclass correlation coefficients
      were used to analyze validity. The ANOVA showed no difference (p=0.089) between
      devices for ACV. However, for PCV, TWAS was significantly different (i.e.
      inaccurate) from OC3D (p<0.001) and OBS (p=0.001), but, OBS was similar (p=0.412)
      to OC3D. For ACV, intraclass correlation coefficients were higher for OBS than
      for TWAS. Bland-Altman plots showed agreement for ACV for both devices against
      OC3D, but large limits of agreement for PCV for both devices. Mountain Plots
      showed valid ACV for both devices, however, but slightly greater ACV and PCV
      accuracy with OBS than TWAS. CONCLUSIONS:: Both devices may provide valid ACV
      measurements, but some metrics suggest more accurate ACV with OBS versus TWAS.
      For PCV neither device is particularly accurate, however, OBS seems to be more
      accurate than TWAS.

PMID- 30300065
TI  - Effects of Water Immersion on Squat and Split-Squat Kinematics in Older Aged
      Adults.
AB  - This study examined the effect of water immersion on trunk and lower limb
      kinematics during squat exercises in older aged participants. Twenty-four active
      older aged adults (71.4 +/- 5.4 yrs.) performed squats and split-squats on land
      and while partially submerged in water. Inertial sensors (100 Hz) were used to
      record trunk and lower-body kinematics. Water immersion increased the squat depth
      (squat: P=0.028, d=0.63, split-squat: P=0.005, d=0.83) and reduced the trunk
      flexion range (squat: P=0.006, d=0.76, split-squat: P<0.001, d=1.35) during both
      exercises. Additionally, water immersion increased the hip range of motion during
      the split-squat (P<=0.002, d=0.94). Waveform analyses also indicated differences
      in the timing of the movements. These results showed that aquatic-based exercise
      generate a different exercise outcome and appear to provide an alternative option
      for older aged adults, allowing these tasks to be performed in a manner that is
      not possible on land.

PMID- 30300066
TI  - Heart Rate Variability in Elite Synchronized Swimmers.
AB  - PURPOSE:: To determine whether heart rate variability (HRV) was correlated with
      other training load and training tolerance markers for monitoring the effect of a
      training session on elite synchronized swimmers. METHODS:: We recorded the
      resting HRVs (Rest) of 12 elite swimmers (mean age: 21.5+/-3.5 yrs) 3 times over
      1 week with a cadence of 48 h prior to the 2015 World Swimming Championships. We
      continuously monitored heart rate (HR) and obtained salivary cortisol (SC)
      samples before and after the last training session of the week. We measured
      capillary blood lactate (Lapeak) 2, 4, and 8 min after the last training session
      and monitored recovery HRV (Rec). We assessed rate of perceived exertion (RPE)
      over the entire session, and we tested the association between Lapeak, SC, and
      RPE and relative changes (Delta%) in the natural logarithm of the root mean
      square successive difference of intervals (LnRMSSD). We also calculated the
      smallest worthwhile change (SWC) of the averaged pre and post LnRMSSD
      measurements. RESULTS:: There were periods of pronounced bradycardia (60.5+/-16.7
      bpm) during training exercises corresponding to apneic exercise. The magnitude
      based inferences showed non clinically meaningful changes of LnRMSSD.Lapeak
      (6.8+/-2.7) was correlated positively with Delta%LnRMSSD and Delta%SC.
      CONCLUSIONS:: There was no change in LnRMSSD, and Lapeak, Delta%SC, and RPE
      indicated reduced sympathetic activation and positive adaptation to the stress
      imposed by the session. Isolated HRV assessment may reveal a controversial
      interpretation of the autonomic nervous system status or the training tolerance
      in elite SS athletes that are influenced by diving response.

PMID- 30300067
TI  - Massive hemorrhage from a unique old cesarean scar ectopic pregnancy with
      negative urine and serum beta-HCG: a rare case report.
AB  - Human chorionic gonadotropin (HCG) is an important indicator for the diagnosis of
      pregnancy. The authors report a unique case of cesarean scar ectopic pregnancy
      (CSEP) with negative urine and serum HCG levels, which was initially misdiagnosed
      as an intrauterine tumor despite the use of transvaginal ultrasound. Dilation and
      curettage was performed, which caused massive vaginal bleeding. Diagnostic
      hysteroscopy after uterine artery embolization and pathological examination of
      the surgical specimen confirmed the diagnosis of old CSEP. Postoperative follow
      up showed that normal menstruation restarted 2 months later. This case reminds
      gynecologists and obstetricians the diagnosis of CSEP should be considered,
      especially when there is a mass at or near the surgical scar, regardless of the
      HCG level.

PMID- 30300068
TI  - Functional hip characteristics and their relationship with ball velocity in
      college baseball pitchers.
AB  - CONTEXT:: Compared to shoulder and elbow functions, the hip functional
      characteristics of baseball pitchers have not been fully investigated. Therefore,
      little is known about the relationship between hip function and pitching
      performance. OBJECTIVE:: The purpose of this study was to evaluate the
      characteristics of hip flexibility and strength focusing on their influences on
      the ball velocity in baseball pitchers. DESIGN:: Descriptive laboratory study.
      SETTING:: Laboratory and University baseball facility. PARTICIPANTS:: Twenty
      three college baseball pitchers. INTERVENTIONS:: Passive hip range of motion
      (ROM) and isometric hip muscle strength were bilaterally measured. The pitchers
      threw 20 fastballs at an official pitching distance. MAIN OUTCOME MEASURES::
      Bilateral hip ROM and strength in flexion, extension, abduction, adduction, and
      external and internal rotation; the maximal ball velocity. RESULTS:: The pivot
      side showed smaller hip external rotation ROM (p < 0.01), larger hip internal
      rotation ROM (p = 0.03), and greater hip adduction strength (p = 0.03) than the
      stride side. The hip extension ROM on the stride side had a negative correlation
      with the maximal ball velocity (r = -0.58, p < 0.01). The maximal ball velocity
      (135.3 +/- 4.1 km/h) positively correlated with the hip extension (r = 0.59, p <
      0.01), flexion (r = 0.57, p < 0.01), abduction (r = 0.55, p < 0.01), and
      adduction (r = 0.55, p < 0.01) strength on the pivot leg, and the hip flexion (r
      = 0.53, p = 0.01), abduction (r = 0.67, p < 0.01), and adduction (r = 0.46, p =
      0.03) strength on the stride leg. CONCLUSIONS:: These findings suggest that
      baseball pitchers do not have marked side-to-side differences in the hip
      flexibility and strength, and that an important fitness factor for increasing
      ball velocity is not the hip flexibility but the hip muscle strength of both
      legs.

PMID- 30300069
TI  - Technical and Tactical Discriminatory Factors Between Winners and Defeated Elite
      Karate Athletes.
AB  - PURPOSE:: The aim of this study was to assess the technical and tactical demands
      of elite karate athletes in relation to three match sequences (i.e., advantage,
      disadvantage, drawing) and match outcome (i.e., win/defeat). METHODS:: One
      hundred and twenty elite seniors (60 males and 60 females) World Karate
      Federation combats were analysed during two World Championships (2012 and 2014).
      Specific karate attributes (strategy, technique, tactic, target and
      effectiveness) were evaluated and classified in three sequences: advantage,
      disadvantage and drawing. RESULTS:: Karatekas performed more combination
      techniques in disadvantage sequences compared to drawing sequences (P=0.011). A
      higher number of timed-attack actions were reported during advantage sequences
      compared to drawing sequences (P=0.048). Winners of the whole combat had higher
      lower-limb technique rate (1.0 +/- 0.9 vs. 0.1 +/- 0.3; P=0.044) and less rate of
      timed-attack (0.3 +/- 0.5 vs. 0.6 +/- 1.0; P=0.030) compared to defeated
      karatekas during advantage- and drawing- sequences, respectively. CONCLUSIONS::
      Winners used higher lower limb technique- and less timed-attack- rates compared
      to defeated karatekas in advantage and drawing sequences, respectively. Indeed,
      using lower limb technique during advantaged situations could be a powerful
      strategy to increase the lead. Therefore, it seems fundamental for coaches of top
      elite karatekas to put their athletes in simulated situation and push them to
      increase the use of lower limb techniques.

PMID- 30300070
TI  - STATIC STRETCHING INTENSITY DOES NOT INFLUENCE ACUTE RANGE OF MOTION, PASSIVE
      TORQUE AND MUSCLE ARCHITECTURE.
AB  - CONTEXT:: Although stretching exercises are commonly used in clinical and
      athletic practice, there is a lack of evidence regarding the methodological
      variables that guide the prescription of stretching programs, such as intensity.
      OBJECTIVE:: The aim of this study was to investigate the acute effects of
      different stretching intensities on the range of movement (ROM), passive torque
      and muscle architecture. DESIGN:: Two-group pretest-posttest design. SETTING::
      Laboratory. PARTICIPANTS:: Twenty untrained men were allocated into the Low (LI)
      or High (HI) intensity group. MAIN OUTCOME MEASURES:: Subjects were evaluated for
      initial (ROMinitial) and maximum (ROMmax) discomfort angle, stiffness,
      viscoelastic stress relaxation (VSR), muscle fascicle length and pennation angle.
      RESULTS:: The ROM assessments showed significant changes, in both groups, in the
      pre- and post-intervention measures, both for the ROMinitial (p<0.01) and ROMmax
      angle (p=0.02). There were no significant differences for stiffness and VSR
      variables. The pennation angle and muscle fascicle length were different between
      the groups, but there was no significant interaction. CONCLUSION:: Performing
      stretching exercises at high or low intensity acutely promotes similar gains in
      flexibility, ie, there are short term/immediate gains in ROM, but does not modify
      passive torque and muscle architecture.

PMID- 30300071
TI  - Clinical and Biomechanical Efficacies of Mechanical Perturbation Training After
      Anterior Cruciate Ligament Rupture.
AB  - CONTEXT:: Manual perturbation training improves knee functional performance and
      mitigates abnormal gait in patients with anterior cruciate ligament (ACL)
      rupture. However, manual perturbation training is time-and labor-intensive for
      therapists. OBJECTIVE:: The purpose of this study was to investigate whether
      perturbation training administered using a mechanical device can provide effects
      similar to manual training on clinical measures and knee biomechanics after ACL
      rupture. DESIGN:: Prospective cohort (therapeutic) study. A 2x2 analysis of
      variance (ANOVA) was used for statistical analysis. SETTING:: A clinical and
      biomechanical laboratory. PATIENTS:: Eighteen Level I/II athletes with acute ACL
      ruptures participated in this preliminary study. INTERVENTION:: Nine patients
      received mechanical perturbation training on an automated mechanical device
      (Mechanical group) and 9 patients received manual perturbation training (Manual
      group). OUTCOME MEASURES:: Patients completed performance-based testing
      (quadriceps strength and single-legged hop tests), patient-reported
      questionnaires (Knee Outcome Survey- Activities of Daily Living Scale, Global
      Rating Score (GRS), International Knee Documentation Committee 2000 (IKDC 2000))
      and 3-D gait analysis before (pre-testing) and after (post-training) training.
      RESULTS:: There was no significant group-by-time interaction found for all
      measures (p>0.18). Main effects of time were found for IKDC 2000 (pre
      testing:69.10+10.95, post-testing:75.14+7.19), knee excursion during weight
      acceptance (pre-testing: 16.01+3.99o; post-testing:17.28+3.99o) and mid-stance
      (pre-testing:14.78+4.13o; post-testing:16.92+4.53o) and external knee flexion
      moment (pre-testing:0.43+0.11 Nm/kg.m; post-testing:0.48+0.11 Nm/kg.m) (p<0.04).
      After accounting for pre-testing groups' differences, mechanical group scored
      significantly higher on triple hops (Mechanical: 96.73+6.65%; Manual:
      84.97+6.83%) and 6-meter timed hops (Mechanical:102.07+9.50%; Manual:
      91.21+9.42%) (p<0.047) compared to manual group. CONCLUSION:: The clinical
      significance of this study is the mechanical perturbation training produced
      effects similar to manual training, with both training methods effective at
      improving patients' perception of knee function and increasing knee excursion and
      external flexion moment during walking after acute ACL rupture. Mechanical
      perturbation training is a potential treatment to improve patients' functional
      and biomechanical outcomes after ACL rupture.

PMID- 30300072
TI  - Calories in Context: Conceptual Metaphors and Consumers' Perception and Use of
      Calorie Information.
AB  - The U.S. Food and Drug Administration (FDA) recently made changes to the
      nutrition facts label so that calories will be emphasized over all other nutrient
      information (U.S. Food and Drug Administration (FDA), 2016a, August 3). In light
      of calories' increased visibility, strategic health communicators need to
      understand both how individuals perceive calorie information and how calories
      influence consumption decisions. Therefore, a qualitative study was conducted to
      analyze the metaphors that structure consumers' thoughts about calorie
      information and food choices. In-depth interviews were conducted with 34 women
      from diverse racial/ethnic and socioeconomic backgrounds. Through the interviews
      and subsequent thematic analysis, metaphors were gathered that explained
      perceptions of different kinds of calories and how calories function in the diet.
      Five conceptual metaphors were uncovered. The metaphors individuals used varied
      based on their eating paradigms, and the metaphors were related to different
      approaches to consumption decisions. The implications of using these different
      calorie metaphors for translational communication interventions are further
      discussed.

PMID- 30300073
TI  - Using a mobile application to assess knee valgus in healthy and post-anterior
      cruciate ligament reconstruction participants.
AB  - CONTEXT:: Popularity of using handheld devices in clinical settings has
      increased, especially the use of motion analysis applications (MAA). Video-based
      measurement tools have been found reliable in measuring knee valgus in subjects
      without anterior cruciate ligament (ACL) injury. However, there is a need for
      validation of using a MAA to measure knee valgus in an injured population given
      that they may exhibit higher degrees of knee valgus. OBJECTIVE:: To examine the
      reliability and validity of using a MAA to measure knee valgus during functional
      activities used to assess return-to-sport after ACL reconstruction (ACLR).
      DESIGN:: Reliability and validity study. SETTING:: University laboratory.
      PARTICIPANTS:: Twelve ACLR participants and 20 healthy individuals.
      INTERVENTIONS:: Each subject performed single-leg drop landing, single-leg hop,
      and 90o cut with simultaneous 3-dimensional (3D) motion capture and video
      recording on an iPad. MAIN OUTCOME MEASURES:: Peak knee valgus during the landing
      phase was measured using MAA and 3D analysis. To obtain reliability, peak knee
      valgus was measured on 2 separate days. Reliability was determined using intra
      class correlation coefficients (ICCs) and standard errors of measurement (SEMs).
      Validity was assessed using Pearson correlation coefficients by comparing peak
      knee valgus between the MAA and 3D analysis. T tests were used to compare knee
      valgus obtained between raters, within raters, and between the MAA and 3D
      analysis. RESULTS:: Our data revealed excellent intra- and inter-rater
      reliability with low SEMs of using a MAA for both groups. Significant, moderate
      to large associations were found in comparing peak knee valgus between the MAA
      and 3D analysis. However, knee valgus was significantly different between the MAA
      and 3D analysis across all tasks in both groups. CONCLUSIONS:: While a MAA is
      reliable for measuring peak knee valgus in individuals with ACLR and healthy
      controls, the actual values obtained by a MAA should be viewed with caution.

PMID- 30300074
TI  - Renal Arterial Pseudoaneurysm After Partial Nephrectomy: Literature Review and
      Single-Center Analysis of Predictive Factors and Renal Functional Outcomes.
AB  - INTRODUCTION AND OBJECTIVE: Partial nephrectomy (PN) represents the current
      surgical standard for T1 tumors. Renal arterial pseudoaneurysm is a rare but
      potentially life-threatening complication reported after PN. The aim of this
      study was to identify the factors associated with the occurrence of
      pseudoaneurysm after PN, specifically focusing on those requiring management with
      selective embolization. A literature review of the topic was performed. METHODS:
      A retrospective review of the institutional PN database was performed from
      January 2011 to December 2016. Patients who underwent embolization for
      pseudoaneurysm represented a separated cohort to be compared with other patients
      (controls). Patients' and tumors' characteristics were considered. Univariable
      and multivariable analyses were used to test their eventual association with the
      occurrence of pseudoaneurysm. RESULTS: A total of 1417 cases were evaluated. At a
      median of 21 days (interquartile range = 10-34), 20 patients (1.4%) developed
      postoperative pseudoaneurysm. The majority of patients (70%) presented with gross
      hematuria. The clinical suspicion was confirmed by contrast-enhanced computed
      tomography scan with angiography. Selective embolization was performed using
      endovascular coils. Technical success and clinical success rates were 100% and
      95%, respectively. No difference was found in percentage estimated glomerular
      filtration rate (eGFR) preserved between patients who underwent embolization
      versus controls (median 82.6% versus 86.3%, P = .35). No differences in age,
      baseline renal function (as assessed by glomerular filtration rate [GFR]), tumor
      size, and R.E.N.A.L. were found between patients who reported and did not report
      pseudoaneurysm. In patients who developed pseudoaneurysm, longer operative time
      (225.6 minutes versus 193 minutes, P = .04), and cold ischemia time (48 minutes
      versus 29 minutes, P = .03) were reported. CONCLUSION: In our series, the
      occurrence of pseudoaneurysm was associated with longer operative and cold
      ischemia times. In patients who underwent selective embolization, renal function
      remained comparable with that of controls.

PMID- 30300075
TI  - The Effects of HighVersus Low-Intensity Power Training on Muscle Power Outcomes
      in Healthy, Older Adults: A Systematic Review.
AB  - Power training (PT) improves muscle power in older adults, however, intensity
      recommendations are less clear. A narrative approach was used to compare high-
      versus low-intensity PT on muscle power (and function) in healthy, older adults.
      Searches were performed using Medline, EMBASE, CINAHL, SPORTDiscus, Ageline, and
      Scopus. Interventions in which older subjects (60+ years) were instructed to
      perform the concentric phase 'as fast as possible' were included. After searches
      were performed, a 3rd category of PT (moderate intensity) was included. Evidence
      from 27 studies (32 PT groups) showed changes in muscle power that averaged
      26.8%, 33.4%, and 21.5%, respectively for high-, moderate-, and low-intensity PT,
      with greater changes with longer training duration and in mildly mobility-limited
      older adults. Function improved similarly across categories. In conclusion, both
      low- and high- intensity PT led to clinically significant changes in power, and
      are viable options for improving power and function in older adults.

PMID- 30300076
TI  - Contraception Update: Extended Use of Long Acting Methods, Hormonal Contraception
      Risks, and Over the Counter Access.
AB  - The clinical update serves as a brief review of recently published, high-impact,
      and potentially practice changing journal articles summarized for our readers.
      Topics include menopause, sexual dysfunction, breast health, contraception,
      osteoporosis, and cardiovascular disease. For this clinical update, we reviewed
      both reproductive and general medical journals for clinically relevant
      publications related to the use of contraceptive methods. We have chosen to
      highlight articles examining the extended use of highly effective (long-acting)
      methods, complications of implants, risks associated with oral combined hormonal
      contraceptives, and the availability of over the counter contraception.

PMID- 30300077
TI  - Relationship Between Obesity and Lumbar Spine Degeneration: A Cross-Sectional
      Study from the Fifth Korean National Health and Nutrition Examination Survey,
      2010-2012.
AB  - BACKGROUND: Although several studies have shown that obesity affects low back
      pain (LBP), the relationship between degenerative lumbar spine (LSD) and obesity
      has not been fully investigated. This study evaluated whether obesity is
      independently associated with LSD in the general population. METHODS: This cross
      sectional study used public data from the Fifth Korean National Health and
      Nutrition Examination Survey (2010-2012). Subjects aged >=50 years who had
      completed surveys were included (3668 men and 4966 women). Obesity was classified
      based on the body mass index, and LSD was assessed by lumbar spine radiographs.
      Independent associations of obesity with LSD or LBP were determined using odds
      ratios (OR) adjusted by two regression models. RESULTS: The prevalence of obesity
      was more frequent in women than in men (38.27% vs. 33.97%, P < 0.001). Compared
      with normal weight women, the risk of LSD was increased in overweight and obese
      women following adjustments [OR = 1.227, 95% confidence interval (CI): 1.019
      1.477; OR = 1.217, 95% CI: 1.024-1.446, respectively]. When obesity was
      subdivided, the obese II group showed higher odds for LSD in women (OR = 1.797,
      95% CI: 1.287-2.510). However, obesity was not correlated with LSD in men. There
      was no significant association between obesity and LBP in either men or women.
      CONCLUSIONS: Compared with normal weight women, LSD risk was higher in overweight
      and obese women, especially those in the obese II subgroup. These findings
      suggest that maintaining normal body weight may be a preventative factor of LSD.

PMID- 30300078
TI  - Assessment of Subfascial Muscle/Water and Fat Accumulation in Lymphedema Patients
      Using Magnetic Resonance Imaging.
AB  - BACKGROUND: In patients with arm or leg lymphedema, more fat has been found in
      the epifascial compartment of the edematous limb compared to the healthy limb.
      However, not much is known about subfascial fat accumulation in these patients.
      This study aims to investigate the intramuscular and intermuscular fat and
      muscle/water volume in lymphedema patients. The excess of intramuscular and
      intermuscular fat volume was also compared to the excess epifascial fat volume,
      the excess limb volume, and the duration of lymphedema. METHODS AND RESULTS: Data
      from 13 patients (seven arm and six leg lymphedemas) were acquired using a 1.5 T
      magnetic resonance imaging (MRI) scanner before liposuction and at five time
      points (4 days, 4 weeks, 3 months, 6 months, and 1 year) after liposuction. From
      water-fat imaging, fat and muscle/water volumes within the intramuscular and
      intermuscular compartments were calculated. The relative excess volume was
      defined as (volume of edematous limb-volume of healthy limb)/volume of healthy
      limb. Elevated relative excess volumes of intramuscular and intermuscular fat
      were found at all time points. A decrease in the relative excess volume of
      muscle/water over time was found. This decrease was not correlated to the
      relative excess of epifascial fat volume, the relative excess of limb volume, or
      the duration of lymphedema. CONCLUSIONS: An excess fat volume was found in the
      intramuscular and intermuscular compartments in lymphedema patients. The results
      suggest that the subfascial compartment needs to be studied separately as no
      correlation between intramuscular/intermuscular fat accumulation and other
      measured parameters was found.

PMID- 30300079
TI  - Trends in Publications on Medical Cannabis from the Year 2000.
AB  - Widespread use of cannabis as a drug and passage of legislation on its use should
      lead to an increase in the number of scientific publications on cannabis. The aim
      of this study was to compare trends in scientific publication for papers on
      medical cannabis, papers on cannabis in general, and all papers between the years
      2000 and 2017. A search of PubMed and Web of Science was conducted. The overall
      number of scientific publications in PubMed increased 2.5-fold. In contrast, the
      number of publications on cannabis increased 4.5-fold and the number of
      publications on medical cannabis increased almost 9-fold. The number of
      publications on medical cannabis in Web of science increased even more (10-fold).
      The most significant number of publications was in the field of psychiatry. In
      the fields of neurology and cancer treatment there was a significant increase in
      the years 2011-2013. There was a rise in the number of publications on children
      and the elderly after 2013. The specific indications with the largest number of
      publications were HIV (261), chronic pain (179), multiple sclerosis (118), nausea
      and vomiting (102), and epilepsy (88). More than half of the publications on
      medical cannabis originated from the United States, followed by Canada. More than
      66% of the publications were original studies. The spike in the number of
      scientific publications on medical cannabis since 2013 is encouraging. In light
      of this trend the authors expect an even greater increase in the number of
      publications in this area in coming years.

PMID- 30300080
TI  - Drawing as an Encoding Tool: Memorial Benefits in Younger and Older Adults.
AB  - : Background/Study Context. In a recent study, drawing pictures relative to
      writing words at encoding has been shown to benefit later memory performance in
      young adults. In the current study, we sought to test whether older adults'
      memory might also benefit from drawing as an encoding strategy. Our prediction
      was that drawing would serve as a particularly effective form of environmental
      support at encoding as it encourages a more detailed perceptual representation.
      METHODS: Participants were presented 30 nouns, one at a time, and asked to either
      draw a picture or repeatedly write out the word, which was followed by a free
      recall test for all words (Experiment 1). In Experiment 2, we added an
      elaborative processing task in which we asked participants to list physical
      characteristics of the objects. In Experiment 3, we probed recognition memory for
      the words. RESULTS: Of the words recalled in Experiment 1, a larger proportion
      had been drawn than written at encoding, and this effect was larger in older
      relative to younger adults. In Experiment 2, we demonstrated that drawing
      improves memory in both younger and older adults more than does an elaborative
      encoding task consisting of listing descriptive characteristics of the target
      nouns. In Experiment 3, older and younger adults drew or wrote out words at
      encoding, and subsequently provided Remember-Know-New recognition memory
      decisions. We showed that drawing reduced age-related differences in Remember
      responses. CONCLUSIONS: We suggest that incorporating visuo-perceptual
      information into the memory trace, by drawing pictures at study, increases
      reliance of the memory trace on visual sensory regions, which are relatively
      intact in normal aging, relative to simply writing out or elaborately encoding
      words. Overall, results indicate that drawing is a highly valuable form of
      environmental support that can significantly enhance memory performance in older
      adults.

PMID- 30300081
TI  - Intra-Dermal Absorbable Suture in the Groin Incision Associated with Less Groin
      Surgical Site Infections than Trans-Dermal Sutures in Vascular Surgical Patients.
AB  - BACKGROUND: The groin surgical site is frequently infected in vascular surgical
      procedures. Our aim was to evaluate the relation of skin closure methods and
      groin incision infection after vascular operations involving femoral artery
      exposure. METHODS: In this retrospective patient record study, patient files of
      all consecutive patients admitted for a vascular procedure to the Turku
      University Hospital Department of Vascular Surgery during 2015-2016 were
      evaluated. Patients with an isolated groin surgical site because of femoral
      artery exposure (256) were included in the study. Patient demographics, details
      of the operations, and follow-up data were collected from the electronic patient
      data record. Statistical analyses were performed using a multi-variable model.
      RESULTS: Altogether, 330 groin incisions were performed for 256 patients. Of all
      incisions, 262 (79.4%) were closed using intra-dermal absorbable suture; trans
      dermal sutures were used in 68 (20.6%) incisions. Groin infections occurred in 24
      (9.2%) patients after skin closure with intra-dermal absorbable suture and in 17
      (25.0%) cases after trans-dermal sutures. Incisions that were closed using trans
      dermal sutures were 3.5 times as likely to have an infection as those closed
      using intra-dermal sutures (odds ratio 3.5, confidence interval 95% 1.6 to 7.6, p
      = 0.002). CONCLUSION: Present data suggest that groin incision closure with intra
      dermal absorbable suture is associated with groin incision infections compared
      with those incisions closed with trans-dermal sutures.

PMID- 30300082
TI  - Update of Recent Literature on Remotely Delivered Psychotherapy Interventions for
      Anxiety and Depression.
AB  - INTRODUCTION: Anxiety and depression are harmful to individuals suffering from
      these disorders, their caregivers, and the economy. Remote delivery of
      psychotherapy has been established as a viable alternative to traditional in
      person psychotherapy for treating anxiety and depression. However, literature
      comparing and evaluating the variety of remote delivery modalities of
      psychotherapy has not yet been integrated. This review examines the efficacy,
      practicality, and limitations of telephone, video, and online-administered
      psychotherapy for the treatment of anxiety and depression. METHODS: A
      comprehensive literature search conducted using PubMed and PsycINFO included
      systematic reviews, randomized controlled trials, and cost-analysis studies
      focused on a remote delivery method of psychotherapy for anxiety and depression.
      RESULTS: Overall, interventions delivered through telephone, video, and online
      modalities demonstrated good efficacy in treating anxiety and depression in
      general, and when presenting comorbid with other disorders. The literature also
      suggested that telehealth psychotherapy is accessible, convenient, and cost
      effective. However, there is less evidence for video-delivered psychotherapy for
      anxiety and depression compared with telephone-administered and online
      administered modalities. Despite this, overall, the efficacy and practical
      benefits of remote psychotherapy interventions in treating anxiety and depression
      across a diverse range of patient groups suggested that it is an appropriate
      alternative for those who cannot access in-person psychotherapy. CONCLUSIONS:
      Further research evaluating the efficacy and practical benefits of video
      delivered psychotherapy for anxiety and depression is much needed for patients
      with limited access to in-person psychological care.

PMID- 30300083
TI  - Hallucination in Adolescence-Or, Nora in Nowhereland Between Neurosis and
      Psychosis.
AB  - The authors present a case history in which they investigate the psychic
      mechanisms behind the production and function of adolescent hallucinations
      against the background of Freud's framework and Laplanche's concept of enigmatic
      messages. They conclude that these hallucinations, although to all appearance
      psychotic, are basically neurotic in nature, and that both their content and
      hallucinatory form serve to protect the defense mechanisms with which parents
      ward off their unconscious conflicts.

PMID- 30300084
TI  - On Reverie and Independence.
AB  - The author presents a detailed clinical discussion of his work with a forty-year
      old man and a ten-year-old boy in which he focuses on loss of self-object
      differentiation in the transference-countertransference experiences while he and
      these two patients were working with tyrannical internal objects (arising from in
      tergenerationally transmitted trauma). In both of the analytic psychotherapies,
      the author experiences reveries in which a benevolent paternal figure lovingly
      supports a child's quest for independence. These reveries are of help to the
      therapist in recognizing, acknowledging, and accepting the need on the part of
      both patients to emancipate themselves from unconscious tyrannizing internal
      objects. The patients had previously experienced their need for emancipation as
      destructive to their parents and themselves, and consequently too dangerous to
      attempt.

PMID- 30300085
TI  - Psyche Singing: Interview With Michael Eigen.
AB  - This interview with Michael Eigen is a conversation about doubt, faith, and three
      influential men, on getting too excited when reading Freud, having a revelation
      come in a dream, and accepting mortality. It's about starting to write and
      breaking things down into smaller pieces, a need to play, the madness in all of
      us, and the basic rhythm of breaking apart and breaking through, and of letting
      the psyche sing.

PMID- 30300086
TI  - Sexual Disgust Redux.
AB  - This critique of Lawrence Josephs's paper on sexual disgust offers an alternate
      understanding of what is meant by the term "relational." To this end, the work of
      Georges Bataille is appropriated toward a relational understanding of sexual
      disgust, both as it relates to the content of the phenomenon and as a model for
      investigation. The perspective adopted from Bataille is then applied to Josephs's
      clinical case material. The critique testifies to the need for a more expansive
      relational perspective, including cross-disciplinary and cross-cultural contact.

PMID- 30300088
TI  - Il deserto rosso.
AB  - The color contrast between the story the protagonist tells in Antonioni's Il
      deserto rosso and the rest of the film points to its oneiric significance. In it
      the otherwise unaccountable removal of the girl's bra is a clue to the repression
      of masturbation and menstruation latent in the recounted story.

PMID- 30300089
TI  - Effects of Resistance Training on Vascular and Hemodynamic Responses in Patients
      With Coronary Artery Disease.
AB  - PURPOSE: The purpose of this study was to determine the impact of adjunctive
      resistance training (RT) in aerobically trained patients with coronary artery
      disease on systolic blood pressure (SBP), heart rate (HR), rating of perceived
      exertion (RPE; using the traditional 6-to-20 scale), and rate-pressure product
      (RPP) responses to lifting fixed submaximal workloads. Additionally, pretest and
      posttest RT measures of brachial artery reactivity were obtained. METHOD: Fifteen
      patients with coronary artery disease (Mage = 66.1 +/- 5.1 years) who were
      already performing regular aerobic exercise completed an adjunctive 12-week
      progressive RT program. Prior to and immediately after the training period,
      hemodynamic responses and RPE were obtained while participants performed one set
      of exercises including the bicep curl (BC), shoulder press (SP), and leg press
      (LP) at individually determined fixed submaximal loads, using ~ 60% to 80% of
      estimated maximal voluntary contraction. Vascular function was assessed by flow
      mediated vasodilation (FMD) testing before and after training. RESULTS:
      Attenuated hemodynamic and RPE responses for all variables were observed.
      Meaningful changes were attained for RPP ([HR * SBP] / 100) during BC (106 +/- 27
      mmHg * beats/min * 10-2 to 91 +/- 22 mmHg * beats/min * 10-2, d = 0.6, p < .05)
      and SP (102 +/- 24 mmHg * beats/min * 10-2 to 86 +/- 17 mmHg * beats/min * 10-2,
      d = 0.8, p < .05). Rating of perceived exertion decreased significantly during
      all exercises (d ranging from 1.8 to 3.1, p < .05): BC (14.3 +/- 2.6 to 9.7 +/-
      1.6), SP (13.9 +/- 1.6 to 9.2 +/- 1.5), and LP (14.3 +/- 1.4 to 10.3 +/- 1.6).
      Peak group FMD responses were 12.8% and 10.3% dilation at pretraining and
      posttraining, respectively (p > .05). Five of the 15 participants showed modest
      improvements in their posttraining time to achieve maximum dilation from a mean
      of 117 s to 81 s, although this change was not statistically significant (p >
      .05). CONCLUSION: Among aerobically trained cardiac patients, a supplemental RT
      program resulted in decreased hemodynamic and RPE responses to lifting fixed
      submaximal workloads.

PMID- 30300091
TI  - CervixCheck: A Spiritually-Based Text Messaging Intervention to Promote Cervical
      Cancer Awareness and Pap Test Screening Intention among African-American Women.
AB  - BACKGROUND/PURPOSE: On a national level, African-American women have a 34% higher
      incidence of cervical cancer and are twice as likely to die of the disease when
      compared to White women. In response to the need to improve cervical cancer
      prevention and Pap test screening knowledge and utilization, we developed and
      pilot tested a 16-day SMS text message-based intervention. The CervixCheck study
      was designed to develop, pilot test, and evaluate the feasibility, acceptability,
      and initial efficacy of a spiritually-based SMS text messaging intervention aimed
      at increasing cervical cancer awareness and Pap test screening intention in
      church-attending African-American women ages 21-65. Methods/Approach: The Theory
      of Planned Behavior guided the development of the CervixCheck intervention. This
      intervention utilized a non-experimental one-group pretest-posttest design. In
      this article, we present findings from the pilot testing phase. Of the 52
      participants at baseline, 46 completed the post-program survey. RESULTS/FINDINGS:
      The current study provides evidence for the early feasibility, high
      acceptability, and some initial efficacy of the CervixCheck intervention. There
      was a significant pre-post increase observed for knowledge about cervical cancer
      and the Pap test (p = .001) and subjective norms (p = .006). Findings post
      intervention also revealed that 83% of participants reported being either
      "satisfied" or "very satisfied" with the CervixCheck intervention and 85% found
      the SMS text messages either "useful" or "very useful". CONCLUSIONS/SIGNIFICANCE:
      A spiritually-based SMS text messaging intervention could be a culturally
      appropriate and cost-effective method of promoting cervical cancer early
      detection information to church-attending African-American women.

PMID- 30300090
TI  - Electrode Equivalence for Use in Bioimpedance Spectroscopy Assessment of
      Lymphedema.
AB  - BACKGROUND: Bioimpedance spectroscopy (BIS) is commonly used in the assessment
      and monitoring of lymphedema. This study investigated electrodes as a source of
      variability that could impact the accuracy of BIS in the clinic and determined if
      Ag/AgCl electrocardiograph (ECG) electrodes could be used as an alternative to
      instrument-specific electrodes. METHODS AND RESULTS: Two types of Ag/AgCl
      electrodes were studied: instrument-specific bioimpedance electrodes
      (bioimpedance) and single tab ECG electrodes (cardiac). Six areas of
      investigation were addressed: intrinsic electrode resistance; electrode age;
      drive electrode position; electrode width/surface area; concordance between
      cardiac and bioimpedance electrodes; and mixing electrode types and batches.
      Participants included women (n = 26) and men (n = 8), both with (n = 4) and
      without lymphedema (n = 30). Resistance (R0) of the limbs was measured and used
      to calculate interlimb BIS ratios. Intrinsic electrode resistance varied between
      batches (p <= 0.001), with cardiac electrodes recording higher resistance.
      Electrode age had no impact on limb resistance (p = 0.85). Drive electrode
      position biased limb resistance (0.1%-2.3%) and electrode size/surface area had a
      small (<=1%), but significant effect on limb resistance (p <= 0.001). However,
      calculation of interlimb BIS ratios negated the impact of these as well as any
      effect of mixing electrode batches and types (p = 0.15-0.96). Electrode type had
      no impact on arm and leg resistance, or interlimb BIS ratios (p = 0.173-0.289).
      CONCLUSION: Calculation of interlimb BIS ratios improves accuracy of clinical
      BIS. Ag/AgCl cardiac electrodes can be used as an alternative to device-specific
      electrodes to measure limb resistance.

PMID- 30300092
TI  - Hypertensive Waist and Lipid Accumulation Product as Predictors of Metabolic
      Syndrome.

PMID- 30300093
TI  - Quality-of-Life Outcomes following Surgical Treatment of Meniere's Disease: A
      Systematic Review and Meta-analysis.
AB  - Objective Several surgical interventions are offered to patients with Meniere's
      disease (MD) who fail medical management. Although outcomes have historically
      been reported according to American Academy of Otolaryngology-Head and Neck
      Surgery guidelines, patient-reported outcome measures (PROMs) are increasingly
      used to evaluate treatments. This study reviews PROMs used to assess surgical
      treatments for MD and compares the effect of each intervention based on PROM
      scores. Data Sources PubMed, EMBASE, CINAHL, and Web of Science. Review Methods
      This is a systematic review and meta-analysis of English-language studies that
      reported PROMs for surgical treatments of MD. Two independent investigators
      assessed study eligibility, rated the quality using Methodological Index for Non
      Randomized Studies (MINORS), and abstracted data for comparative analysis. A
      random-effects model was used for meta-analysis of pooled data. Results Of 148
      unique studies identified, 11 satisfied inclusion criteria. The Meniere's Disease
      Outcome Questionnaire (MDOQ) was the most commonly used survey. Interventions
      included intratympanic gentamicin, vestibular nerve section, endolymphatic sac
      surgery, and labyrinthectomy. Pooled analysis of 8 studies that used the MDOQ
      instrument demonstrated statistically significant improvements in quality of life
      but did not identify a difference between destructive and nondestructive
      procedures. Conclusion Although our review shows significant improvements in PROM
      scores for both destructive and nondestructive interventions, there was no
      significant difference noted between treatment types. We cannot draw conclusions
      regarding the comparative effectiveness of specific interventions, and the
      results do not account for placebo effects or the natural history of the disease.
      Further investigation with randomized controlled trials should be considered in
      future studies.

PMID- 30300094
TI  - Neuronomy, education, and outreach in neuroscience: A historical case study of
      Burt Green Wilder.
AB  - Burt Green Wilder (1841-1925) was a pioneering naturalist and anatomist who is
      historically known for his brain collection and for his contributions to
      neuroanatomical nomenclature. During his 42-year career, Wilder also used brain
      measurements for education and outreach, especially in regard to issues of race
      and gender. Additionally, Wilder influenced neuroscience education and acted as a
      scientific liaison to the public. For example, he designed early implementations
      of the sheep brain dissections that are still being conducted today, as well as
      likely conducted the first "Brain Day." This article reviews each of these
      topics, as well as others, with the aim of accurately placing Wilder in the
      history of neuroscience as a naturalist and anatomist who, among other
      achievements, pioneered the use of brain measurements for education and outreach.

PMID- 30300095
TI  - Thoracoscopic Treatment of Late-Presenting Congenital Diaphragmatic Hernia in
      Infants and Children.
AB  - PURPOSE: Given that the application of thoracoscopic surgery to late-presenting
      congenital diaphragmatic hernia (CDH) in infants and children is controversial,
      we summarized our experiences with patients at two medical centers and aimed to
      discuss the safety and feasibility of thoracoscopic repair. MATERIALS AND
      METHODS: A retrospective review of late-presenting CDH cases involving patients
      who underwent thoracoscopic repair from October 2010 to June 2017 was performed.
      Data, including patients' demographic characteristics, manipulative details, and
      postoperative complications, were extracted and analyzed. RESULTS: A total of 59
      cases were included in this study. Patients ranged in age from 2 months to 8
      years (mean: 18 months). Twenty-five patients presented with shortness of breath
      and dyspnea. Furthermore, 34 cases were found occasionally. Forty-six left-sided
      hernias and 13 right-sided hernias were found. Operating time ranged from 30 to
      100 minutes (mean: 55 minutes), and the amount of blood loss was 3-5 mL (mean:
      3.8 mL). The size of the diaphragmatic defect ranged from 2 * 2 cm to 5 * 8 cm.
      The chest tubes were taken out within 24 hours. The average length of
      postoperative hospital stay was 5.2 +/- 0.4 days (range: 4-6 days). The length of
      the follow-up period ranged from 3 months to 3 years (mean: 18 months), with no
      recurrences. CONCLUSION: Thoracoscopic repair of late-presenting CDH is a safe
      and efficacious technique. It can facilitate the procedure and decrease the
      recurrence rate by shifting the focus to operative details. The prognosis is
      excellent once the correct operative details are achieved.

PMID- 30300096
TI  - Characteristics of biochars prepared by co-pyrolysis of sewage sludge and cotton
      stalk intended for use as soil amendments.
AB  - The safe disposal and utilisation of sewage sludge can be challenging because of
      the potential environmental risks posed by heavy metals in the sludge. Conversion
      of sewage sludge and agriculture biomass into biochars that can be used to
      improve or remediate contaminated soils is a promising solution to this problem.
      In this study, biochars were produced via co-pyrolysis of sewage sludge and
      cotton stalk (1:1, w/w) at temperatures ranging from 300 degrees C to 600 degrees
      C. Then, the potential environmental risks of heavy metals and properties of the
      biochars were investigated. The addition of cotton stalk promoted the migration
      and transformation of heavy metals from bioavailable to stable fractions, which
      significantly reduced the potential environmental risks of heavy metals in
      biochars. Moreover, compared with biochars obtained via pyrolysis of sewage
      sludge alone, the pH values, C contents, and adsorption capacities of biochars
      increased, while the yields, ash contents, specific surface areas and molar H/C
      ratios decreased. In summary, co-pyrolysis of sewage sludge and cotton stalk is a
      feasible method for alleviating the potential environmental risks of heavy metals
      in biochars used to treat soils.

PMID- 30300097
TI  - A Single-Center Experience: The Diagnostic Role of Peritoneoscopy in Patients
      with Exudative Ascites.
AB  - BACKGROUND AND AIM: The causes of exudative and transudative ascites can be
      detected through noninvasive methods nowadays. In selected cases, peritoneoscopy
      could be necessary for definitive diagnosis. In this retrospective study, we
      aimed to present the peritoneal biopsy results of patients who had exudative
      ascites with unclear etiology. MATERIALS AND METHODS: A retrospective analysis
      was performed in 86 patients who had exudative ascites of unclear etiology. All
      the patients showed abnormalities of the peritoneum or greater omentum as
      determined by abdominal ultrasonography and underwent peritoneoscopy between
      January 2012 and December 2015. Patient data were obtained from hospital records.
      RESULTS: Eighty-six patients (male: 22; 25.6%, mean age +/- standard deviation:
      57.97 +/- 15.97) who had exudative ascites of unclear etiology were included to
      the study. The success rate of the procedures was 100% (86/86). A specific
      histopathological diagnosis was made in all patients, with an overall diagnostic
      accuracy of 100%. Among the 86 diagnosed patients, 43 (50%) were peritonitis
      carcinomatosa, 21 (24.4%) were tuberculous peritonitis, 14 (16.3%) were
      mesothelioma, 4 (4.7%) were chronical inflammation, and 1 (1.2%) was lymphoma.
      Three (3.5%) patients had normal peritoneal biopsy findings. DISCUSSION:
      Peritoneoscopy is a safe and efficient alternative method due to its high
      diagnostic capacity in selected patients who have exudative ascites of unclear
      etiology.

PMID- 30300098
TI  - The Influence of Ankle Braces on Functional Performance Tests and Ankle Joint
      Range of Motion.
AB  - CONTEXT:: The lateral ankle sprain is one of the most common lower extremity
      injuries in sports. Previous research has found that some prophylactic ankle
      supports reduce the risk of recurrent ankle sprains and provide extra support to
      the joint. However, there is a continued concern that these supports may
      negatively influence performance. OBJECTIVE:: To determine if wearing an ankle
      brace influences athlete performance and ankle kinematics during functional
      performance tests (FPTs). DESIGN:: Repeated measures. SETTING:: University
      Gymnasium. OTHER PARTICIPANTS:: Male and female recreational or competitive
      athletes (n=20). INTERVENTION:: Participants performed three trials of a standing
      long jump, vertical jump, 40 yard sprint, and T-drill under each of the following
      three conditions: wearing traditional lace-up brace (brace 1), modified lace-up
      brace (brace 2), and no-brace. MAIN OUTCOME MEASURES:: A 2D motion capture camera
      was used to measure ankle range of motion (ROM) in the sagittal plane during the
      vertical and standing long jumps and in the frontal plane during the cutting
      phase of the T-drill. Performance of each test and ankle ROM were compared
      between each of the braced conditions. RESULTS:: Ankle braces did not influence
      performance in speed or agility FPTs (p>0.05). Ankle braces negatively affected
      performance of the standing long jump (p=0.01) and vertical jump (p=0.01). There
      was no significant difference between brace or no-brace conditions in ankle
      inversion ROM during the T-drill (p>0.05). Both brace conditions restricted ROM
      in the sagittal plane during the vertical and standing long jumps (p<0.05).
      CONCLUSIONS:: Braced conditions restricted sagittal plane ROM during the vertical
      jump and long jump. This decrease in ROM explains the decline in functional
      performance also seen during these tests.

PMID- 30300099
TI  - Early Low-Level Laser Therapy Improves the Passive Range of Motion and Decreases
      Pain in Patients with Flexor Tendon Injury.
AB  - BACKGROUND: To obtain the best result from flexor tendon repair surgery, proper
      surgical technique, appropriate materials, good rehabilitation, and patient
      satisfaction are essential to consider. Nevertheless, no general unique protocol
      still exists between researchers, for a suitable treatment plan. OBJECTIVE: The
      aim of the present random clinical trial (RCT) was to determine the adjuvant
      effect of low-level laser therapy (LLLT) on healing tendon injury in patients.
      MATERIALS AND METHODS: In an RCT, 97 patients (114 fingers) with sharp injury in
      three zones of their hands were randomly divided into LLLT and control groups,
      using the unequal treatment allocation approach. Thirty-nine patients (31 males
      and 8 females, 46 fingers) were enrolled in the LLLT group, receiving 8-10
      sessions of LLLT (red and infrared lasers) over the flexor tendon repaired area.
      In the control group, 58 patients were included, 20 patients did not come back
      for follow-up, and 38 patients (29 males and 9 females, 46 fingers) participated
      in the study. Patients were visited in days 28 - 32 after surgery. Passive range
      of motion (PROM), pain severity of groups, and patient satisfaction from LLLT
      were all recorded. The two observers, blind to the LLLT group assessed the data
      independently. RESULTS: In two groups, no rupture was observed during 4 weeks
      postsurgery. None of the patients in the control group was able to perform the
      full passive flexion. There was a significant increase in PROM (t = 82.925, p =
      0.000) and a significant pain reduction (t = -11.96, p = 0.000) in the LLLT
      group, compared with the control group. All Patients in the LLLT group were
      satisfied. CONCLUSIONS: LLLT is a proper adjuvant therapy in flexor tendon
      repair. Evidently, LLLT promotes tendon healing, alleviates the pain, and assists
      flexibility of soft tissue and joints, leading to the tremendous improvement in
      patient cooperation and compliance.

PMID- 30300101
TI  - The Relationship between Post-Battle Experiences and Thwarted Belongingness and
      Perceived Burdensomeness in Three United States Military Samples.
AB  - Suicide rates within the military are elevated relative to the general
      population; however, research suggests that many of the suicide risk factors for
      military personnel are similar to the suicide risk factors for civilians. Given
      that many military specific experiences (e.g., number of deployments) are not
      considered robust predictors of either suicidal ideation or behavior, it has been
      posited that deployment specific experiences (e.g., post-battle experiences) may
      be better able to explain the increased rates of suicide among military
      personnel. Therefore, the current study aimed to examine the relationship between
      post-battle experiences and perceived burdensomeness (PB), thwarted belongingness
      (TB), and suicidal ideation within 3 different military samples: a non-clinical
      sample of Army National Guard personnel, a non-clinical sample of active duty
      U.S. Air Force Security Forces personnel, and a clinical sample of U.S. Army
      personnel receiving outpatient treatment. Post-battle experiences were found to
      be significantly associated with TB in both non-clinical samples; however, the
      association between post-battle experiences and TB was non-significant within the
      clinical sample. Furthermore, results indicated that post-battle experiences were
      not significantly associated with either PB or suicidal ideation in any of the
      samples. These findings suggest that in non-clinical samples, post-battle
      experiences impact a soldier's ability to feel connected to others. Within
      clinical samples, results indicate that post-battle experiences may not be a
      direct contributor to either PB or TB. These results indicate a need for
      universal intervention promoting interpersonal support of military personnel and
      their families prior to development of further need for psychological
      interventions. This upstream approach may decrease further development of TB and
      potentially prevent suicidal desire.

PMID- 30300100
TI  - Does the Improvement of Position Sense Following Motor Imagery Practice Vary as a
      Function of Age and Time of Day?
AB  - The effectiveness of motor imagery practice is known to depend on age and on the
      ability to form motor images. In the same individual, motor imagery quality
      changes during the day, being better late in the morning for older adults and in
      the afternoon for younger adults. Does this mean that motor imagery practice
      should be done at specific time of the day depending on the age of participants
      to maximize motor learning? To examine whether the effect of motor imagery
      practice varies as a function of time of day and age, the authors used an arm
      configuration reproduction task and measured position sense accuracy before and
      after 135 kinesthetic motor imagery trials. Younger and older participants were
      randomly assigned to either a morning or an afternoon session. Data showed that
      the accuracy for reproducing arm configurations improved following imagery
      practice regardless of time of day for both younger and older adults. Moreover,
      the authors observed that the position sense was less accurate in the afternoon
      than in the morning in older participants (before and after motor imagery
      practice), while performance did not change during the day in younger
      participants. These results may have practical implications in motor learning and
      functional rehabilitation programs. They highlight the effectiveness of motor
      imagery practice for movement accuracy in both younger and older adults
      regardless of time of day. By contrast, they reveal that the assessment of
      position sense requires that the time of day be taken into account when
      practitioners want to report on the older patients' progress without making any
      mistakes.

PMID- 30300102
TI  - Dissemination of the Safety Planning Intervention (SPI) to University Counseling
      Center Clinicians to Reduce Suicide Risk among College Students.
AB  - OBJECTIVE: Suicide risk on college campuses remains a pervasive problem.
      Structural deficits in current clinical care models often result in sub-optimal
      treatment for suicidal students. This study reports on the feasibility,
      acceptability and utility of the Safety Planning Intervention (SPI), a brief,
      empirically-validated, clinician-administered suicide prevention intervention, in
      a university counseling center (UCC) setting. METHODS: Twelve university
      counseling center direct service staff completed a 2-hour training in SPI.
      Participants reported on suicide intervention practices, training needs, and
      confidence at baseline and 10 weeks post-training. Acceptability, utility, and
      frequency of SPI use were assessed at follow-up. RESULTS: All clinical staff
      attended the training and found it useful, reporting that confidence in managing
      suicide risk increased as a result. Two-thirds of staff implemented SPI least
      once. CONCLUSION: Results suggest that SPI is a feasible, acceptable, and useful
      suicide intervention tool for UCCs.

PMID- 30300103
TI  - Parental emotion regulation and preschoolers' prosocial behavior: The mediating
      roles of parental warmth and inductive discipline.
AB  - The potential mediating roles of parental warmth and inductive discipline on the
      relations of parental emotion regulation strategies to children's prosocial
      behavior were examined in this study. Sixty-four parents of preschoolers (50%
      girls) completed questionnaires assessing their own regulation practices (i.e.,
      cognitive reappraisal, expressive suppression), parenting behaviors (i.e.,
      parental warmth/nurturance, inductive discipline), and children's prosocial
      behavior (voluntary behavior intended to benefit another). The authors
      hypothesized that cognitive reappraisal would be positively and expressive
      suppression would be negatively related to parenting behaviors and children's
      prosocial behavior. They further hypothesized that parental warmth and inductive
      discipline would mediate the relations between parents' own regulation strategies
      and children's prosocial behavior. Results demonstrated that parental cognitive
      reappraisal was positively associated with warmth, and expressive suppression was
      negatively associated with inductive discipline and children's prosocial
      behavior. Parental warmth, but not inductive discipline, mediated the relations
      between cognitive reappraisal and children's prosocial behavior. The results
      highlight adults' own regulatory strategies as predictors of socialization
      behaviors and the potential processes for socialization of children's moral
      emotions and positive social development.

PMID- 30300104
TI  - Effects of Gain- and Loss-Framed Quit Messages on Smokers: Test of the Ability to
      Process the Health Message as a Moderator.
AB  - Health messages can emphasize the benefits of engaging in healthy behavior (gain
      framed) or the costs of failing to engage in it (loss-framed). Previous research
      revealed that gain-framed messages tend to be more effective in motivating
      smokers to quit. As a supplement to previous studies, we questioned whether the
      ability to process health messages moderates the size of the gain-frame
      advantage. There were two competing theoretical ideas. First, some scholars have
      noted that a high ability to process a health message is a necessary precondition
      to observe the advantage of gain-framing. Second, risk aversion-a central concept
      used in previous theorizing to explain the gain-frame advantage-is associated
      with automatic processing and automatic processing has a stronger influence on
      decision making under a low ability to process. We utilized a 2 (exposure to gain
      or loss-framed quit messages) * 2 (low or high ability to process) randomized
      controlled trial with a pre-post exposure change in quit intentions as the target
      outcome (N = 182 smokers). Although the analysis revealed the hypothesized gain
      frame advantage, the ability to process did not moderate the effect. We discuss
      the theoretical implications.

PMID- 30300106
TI  - The impact of different product formats on inaction inertia.
AB  - The inaction inertia effect describes situations in which a person rejects an
      opportunity after having forgone a relatively superior opportunity. This study
      explores whether product format (hedonic vs. utilitarian) affects the inaction
      inertia effect. The authors build on previous findings that show comparisons of
      utilitarian benefits are easier than hedonic benefits, and hedonic consumption
      (vs. utilitarian consumption) usually generates greater pleasure. The authors
      propose that people show higher inaction inertia after they have missed a
      superior utilitarian consumption opportunity than after they have missed a
      superior hedonic consumption opportunity. This prediction was tested and
      supported in three different experiments. Moreover, the authors found that
      differences in comparability between products, rather than the hedonic pleasure,
      explain differences in inaction inertia effects. These findings contribute to the
      inaction inertia literature and marketing practice.

PMID- 30300105
TI  - A case study on breastfeeding education in Lebanon's public medical school:
      exploring the potential role of social networks in medical education.
AB  - BACKGROUND: Limited knowledge, negative beliefs, and lack of sufficient
      breastfeeding promotion and support by physicians contribute to global suboptimal
      breastfeeding rates. Formal medical education is well-known to influence future
      physicians' knowledge, beliefs, and medical practice. However, less understood is
      the influence of social networks and processes on the exchange and diffusion of
      knowledge and practices related to breastfeeding. OBJECTIVES: We selected the
      underserved and under-supported public medical school in Lebanon to examine the
      social side of medical education. Our objectives were to assess knowledge,
      beliefs, and self-efficacy related to breastfeeding promotion and support among
      interns and residents. We also examined the social ecosystem surrounding these
      students concerning the exchange of breastfeeding knowledge. DESIGN: All data
      were collected during one study visit per participant. First, an interview
      administered structured survey was used to assess beliefs, perceived knowledge,
      basic breastfeeding knowledge, and self-efficacy related to breastfeeding among n
      = 70 medical interns and residents. Then, social network data were collected
      during a semi-structured interview and analyzed using an ego-network approach.
      All interviews were voice-recorded, transcribed, coded, and thematically
      analyzed. Descriptive statistics were used to analyze quantitative survey and
      social network results. RESULTS: Although interns and residents had positive
      beliefs about breastfeeding benefits, they had limited knowledge and low self
      efficacy related to the psychosocial and clinical aspects of breastfeeding
      promotion and support. They did not seem to have a well-connected professional
      network around breastfeeding knowledge and practices. Several tended to rely on
      their informal/non-professional network, such as their mothers, partners, and
      sisters, for knowledge and practice. CONCLUSIONS: Our work using breastfeeding as
      an exemplary case suggests there is a role for better attending to the beliefs of
      medical students as well as to the social side of medical education. Future
      studies can use social network theory to help identify and address influences on
      medical education outcomes.

PMID- 30300107
TI  - Fathers and Perceptions of God Play an Important Role in Psychological Adjustment
      Among Emerging Adults in Guatemala and the United States.
AB  - Interpersonal acceptance-rejection theory posits that people require parental
      acceptance in childhood to develop healthy psychological adjustment. People's
      beliefs about and their relationship with deity also influences their
      psychological adjustment. The purpose of the present study was to investigate how
      both perceived parental acceptance and a relationship with deity are related to
      psychological adjustment for emerging adults in Guatemala and the United States.
      Participants (N = 189) from Guatemala and the United States completed measures of
      perceived parental acceptance-rejection, images of God, attachment to God, and
      psychological adjustment. Results indicate that perceived paternal acceptance
      rejection was only a significant predictor of psychological adjustment in U.S.
      participants, and not in Guatemalan participants. In both samples, images of God
      did not predict psychological adjustment. However, an anxious attachment with God
      predicted psychological maladjustment for both groups. The findings suggest that
      two important factors to be considered by researchers, educators, and mental
      health professionals are adults' perceptions of their father's level of
      acceptance-rejection and the amount of anxiety they experience in their
      relationship with God.

PMID- 30300108
TI  - Effects of psychological distance on attraction effect.
AB  - The present study demonstrated that psychological distance influences the
      attraction effect by changing the weights of the attributes of options. Construal
      level theory proposes that the weight of a superordinate attribute increases with
      psychological distance, whereas the weight of a subordinate attribute decreases
      with psychological distance. The present hypothesis proposed that an asymmetrical
      change of weights of attributes would influence the relationship between options,
      and, consequently, the attraction effect would vary. The present study comprised
      two studies. In study 1, participants made choices among three lotteries in near
      and distant future conditions. Study 2 asked the participants to choose among
      three events in similar and dissimilar other conditions. The results showed that
      the choice of the asymmetrically dominating option, which was superior in
      superordinate attributes, increased as the psychological distance increased,
      whereas the choice of the asymmetrically dominating option, which was superior in
      subordinate attributes, decreased or stayed static.

PMID- 30300109
TI  - Challenges for Japanese rural home care workers in interprofessional
      collaboration: a qualitative study.
AB  - Among medical professionals, the role of home care workers is crucial in the care
      of patients in their homes. In Japan, however, research on the difficulties home
      care workers face while working in rural zones is limited. Using thematic
      analysis, a qualitative study was conducted with 57 home care workers in a rural
      area of Japan. Findings revealed the difficulties they experienced regarding the
      medical problems of their patients and in their relationships with other
      professionals. The old customs of rural medicine and the system of long-term care
      insurance strongly influence relationships among multiprofessionals, leading to
      conflict and hierarchy.

PMID- 30300110
TI  - Experimental Infection and Transmission Competence of Sindbis Virus in Culex
      torrentium and Culex pipiens Mosquitoes from Northern Sweden.
AB  - INTRODUCTION: Sindbis virus (SINV) is a mosquito-borne Alphavirus known to infect
      birds and cause intermittent outbreaks among humans in Fenno-Scandia. In Sweden,
      the endemic area has mainly been in central Sweden. Recently, SINV infections
      have emerged to northern Sweden, but the vectorial efficiency for SINV of
      mosquito species in this northern region has not yet been ascertained. OBJECTIVE:
      Mosquito larvae were sampled from the Umea region in northern Sweden and
      propagated in a laboratory to adult stage to investigate the infection,
      dissemination, and transmission efficiency of SINV in mosquitoes. MATERIALS AND
      METHODS: The mosquito species were identified by DNA barcoding of the cytochrome
      oxidase I gene. Culex torrentium was the most abundant (82.2%) followed by Culex
      pipiens (14.4%), Aedes annulipes (1.1%), Anopheles claviger (1.1%), Culiseta
      bergrothi (1.1%), or other unidentified species (1.1%). Mosquitoes were fed with
      SINV-infected blood and monitored for 29 days to determine the viral extrinsic
      incubation period. Infection and dissemination were determined by RT-qPCR
      screening of dissected body parts of individual mosquitoes. Viral transmission
      was determined from saliva collected from individual mosquitoes at 7, 14, and 29
      days. SINV was detected by cell culture using BHK-21 cells, RT-qPCR, and
      sequencing. RESULTS: Cx. torrentium was the only mosquito species in our study
      that was able to transmit SINV. The overall transmission efficiency of SINV in
      Cx. torrentium was 6.8%. The rates of SINV infection, dissemination, and
      transmission in Cx. torrentium were 11%, 75%, and 83%, respectively. CONCLUSIONS:
      Cx. torrentium may be the key vector involved in SINV transmission in northern
      Sweden.

PMID- 30300111
TI  - Couples' employment after spousal kidney donation.
AB  - We used data from the United Network for Organ Sharing registry of living kidney
      donors and recipients to identify correlates of paid employment among couples
      following spousal living donation. Among such couples, post-transplant employment
      of both spouses (41%) was as common as employment of the donor only (41%).
      However, when the recipient was female, donor-only employment after transplant
      was more than twice as likely as compared to employment of both spouses (relative
      risk ratio = 2.57; p < .001). We conclude that traditional gender roles regarding
      paid workforce participation may be associated with the likelihood of employment
      after spousal kidney donation.

PMID- 30300112
TI  - The SIC Scale of Ageism: Confirmatory Factor Analysis, Measurement Invariance,
      and Revisions.
AB  - The present study seeks to confirm the factor structure of the succession,
      identity, and consumption (SIC) scale of prescriptive ageism as a modern measure
      of intergenerational ageism, with particular utility for institutionalized ageism
      and policy in health care, the workplace, and residential facilities. In
      addition, measurement invariance of the scale is tested for gender and
      racial/ethnic groups. Confirmatory factor analysis was performed on the scale as
      initially proposed, treating the items as categorical variables (see for
      treatment of Likert-type items as categorical). Modifications to the scale were
      explored using both theoretical and statistical criteria. Measurement invariance
      tests were run on both gender and racial/ethnic categories. Analyses indicated
      that the three-factor structure as initially proposed was validated in an
      undergraduate population. Minor modifications are proposed to improve the
      performance of the measure. Using comparative fit indices, measurement invariance
      was established for gender and racial/ethnic groups with mean level scale score
      differences discussed.

PMID- 30300113
TI  - Development of a Quantitative RT-PCR Assay to Differentiate Rift Valley Fever
      Virus Smithburn Vaccine Strain from Clone 13 Vaccine Strain.
AB  - A new quantitative RT-PCR assay was developed to differentiate Rift Valley fever
      (RVF) Smithburn vaccine strain from Clone 13 vaccine strain. The new qRT-PCR
      assay targeting the S segment (NSs and N gene) was tested on synthesized standard
      RNA and MP-12 strain viruses. The detection limit of the new qRT-PCR assay is 1
      copy/MUL of NSs and N, and is able to differentiate the Smithburn vaccine strain
      of RVF from the Clone 13 vaccine strain. No cross-reactivity with other vector
      borne viruses was observed, a factor that is especially important in the Republic
      of Korea (ROK). To examine the performance of the qRT-PCR, intra- and inter-assay
      variability data were analyzed and showed high reproducibility. These results
      indicate that the new qRT-PCR can be used as a safe and cost-effective test.
      Furthermore, this result suggests the possibility of differentiation between
      infected and vaccinated animals diagnostic test in RVF-free countries including
      ROK.

PMID- 30300114
TI  - The Impact of Widely Publicized Suicides on Search Trends: Using Google Trends to
      Test the Werther and Papageno Effects.
AB  - OBJECTIVE: To examine the impact of widely publicized suicides on the Werther and
      Papageno Effects using internet search trends. METHOD: A list of widely
      publicized suicides from 2010 through 2018 was compiled along with dates of death
      for each of these individuals. Google.com/trends data was then collected for
      searches for "how to suicide" and "suicide prevention" for 14 days prior to a
      widely publicized suicide/14 days after a widely publicized suicide and 7 days
      prior to a widely publicized suicide/7 days after a widely publicized suicide.
      Comparisons were then made between these time periods for "how to suicide" and
      "suicide prevention." RESULTS: Some celebrities, such as Robin Williams (2014)
      and Aaron Hernandez (2017) were associated with increased searches. However, for
      many there was no increase in search trends. CONCLUSIONS: Limited support was
      found for the impact of widely publicized suicides on internet search trends with
      one case supporting a Werther Effect and one case supporting a Papageno Effect.
      The finding that only some celebrities were associated with increased searches
      may be a byproduct of the impact of celebrity status on these effects, with more
      prominent celebrities having the greatest impact.

PMID- 30300115
TI  - Social workers, nurses, or both: Who is primarily responsible for hospital
      discharge planning with older adults?
AB  - This study examines the profession primarily responsible for discharge planning
      in all hospitals serving older adults in Minnesota. Quantitative analyses
      determined that the majority of hospitals in Minnesota serving older adults are
      small, rural hospitals with critical access designations, are private nonprofit,
      and are affiliated with a health care system. Social workers are primarily
      responsible for discharge planning in half of the hospitals, nurses in a quarter
      and either a nurse/social worker team or both nurse and social worker separately
      in the remaining quarter. Multinomial logistic regression determined that in
      critical access hospitals nurses are more likely than social workers to be the
      profession primarily responsible for discharge planning.

PMID- 30300117
TI  - Reliability and Validity of the Trauma Symptom Checklist for Children and Trauma
      Symptom Checklist for Young Children Screeners in a Clinical Sample.
AB  - This study reports on the reliability and validity for two measures developed for
      screening of symptoms in child sexual abuse (CSA)-the Trauma Symptom Checklist
      for Children-Screening Form (TSCC-SF) and the Trauma Symptom Checklist for Young
      Children-Screening Form (TSCYC-SF). The sample of 200 children and caregivers
      received outpatient treatment. Internal consistencies ranged from an alpha of
      0.79-0.85. Concurrent validity was demonstrated by correlations with the TSCC and
      TSCYC. The TSCC-SF General Trauma (GT) was only correlated Child Behavior
      Checklist (r = .236 for the Anxious Depressed Scale with the TSCC GT; however,
      all Child Behavior Checklist scales correlated with the TSCYC GT ranging from
      .422 to .692, and with the SC with r = .713), and the Children's Attributional
      and Perceptual Scale. Findings support reliability and validity reported
      elsewhere. The TSCC-SF and TSCYC-SF show promise for screening and triage of CSA
      victims in many settings.

PMID- 30300116
TI  - The long coding RNA AFAP1-AS1 promotes tumor cell growth and invasion in
      pancreatic cancer through upregulating the IGF1R oncogene via sequestration of
      miR-133a.
AB  - Long non-coding RNAs (lncRNAs) have been shown to play a significant role in the
      progression of many cancers, including pancreatic cancer (PC). However, the
      biological function and regulatory mechanisms of lncRNAs in PC remains largely
      unclear. The aim of this study was to identify and evaluate the potential
      functions of lncRNAs in PC and reveal the underlying mechanisms of their effects.
      Screening of published microarray data (GEO accession Nos. GSE16515 and
      GSE32688), revealed lncRNA AFAP1-AS1 to be one of the most upregulated lncRNAs in
      PC tissues. High expression of AFAP1-AS1 was correlated with advanced stages,
      tumor size and lymph node metastasis, as well as with poorer overall survival in
      patients with PC. Functionally, knockdown of AFAP1-AS1 by transfection with siRNA
      inhibited the proliferative and invasive capacities of PaCa-2 and SW1990 PC
      cells, promoted apoptosis of PC cells in vitro, and impaired in-vivo
      tumorigenicity. In particular, it was hypothesized that AFAP1-AS1 may act as a
      competitive endogenous RNA (ceRNA), effectively becoming a sink for miR-133a
      whose expression was found to be downregulated in PC tissues and cell lines, and
      which was negatively correlated with the expression of AFAP1-AS1. We also found
      that the IGF1R oncogene which is an important regulator of MEK/ERK signaling
      pathway, was positively regulated by AFAP1-AS1 through ameliorating miR-133a
      mediated IGF1R repression in PC tissues. Moreover, we demonstrated that knockdown
      of IGF1R by transfection with si-IGF1R suppressed cell proliferation, invasion
      and migration of PaCa-2 and SW1990 PC cells, suggesting that IGF1R may function
      as an oncogene in PC cells. Further investigations revealed that miR-133a
      reversed the biological effects of AFAP1-AS1 on PC cells. Collectively, the
      findings provide new evidence that AFAP1-AS1 could regulate the progression of
      pancreatic cancer by acting as a ceRNA, and suggest it has potential for use as
      both a biomarker for the early detection PC and for the development of
      individualized therapies for PC.

PMID- 30300119
TI  - Potential Mood Variation Following a Behavioral Analogue of Self-Injurious
      Behavior.
AB  - Despite increased use of behavioral analogues to identify casual mechanisms of
      self-injurious behavior (e.g., suicide attempts; non-suicidal self-injury),
      little is known about the impact on participants. The current study examined the
      impact of a specific behavior analogue, Self-Aggressive Paradigm (SAP), on
      participant affect. Community participants (n = 507) reported several affective
      ratings before and after completing SAP task procedures. Following the SAP,
      participants reported reductions in nervousness and fear and increases in
      calmness and anger (d = .21). Participants with a current anxiety disorder
      reported greater increases in happiness; those with a suicide attempt history
      reported greater increases in sadness. Findings demonstrate the SAP has no
      adverse mood effects, supporting its use in experimental research.

PMID- 30300118
TI  - Gestational diabetes and macrosomia among Greenlanders. Time to change diagnostic
      strategy?
AB  - : Gestational diabetes mellitus (GDM) is a serious condition associated to both
      maternal and offspring complications. Yet, no globally accepted consensus exists
      on how to test and diagnose GDM. In Greenland, the clinical criteria for testing
      and diagnosing GDM are adapted from Danish guidelines. The aim of this study was
      to estimate the prevalence of GDM among Greenlanders using both the current
      clinical GDM criteria and the recent WHO 2013 criteria and, further, to study the
      association between GDM, pre-pregnant overweight or obesity and macrosomia. A
      cross-sectional study of all 450 Greenlandic women who gave birth to a singleton
      in Nuuk within 1 year was performed. Based on an oral glucose tolerance test
      measuring capillary whole blood glucose, 119 women were categorised as having
      clinical GDM, WHO 2013 GDM or not GDM. Macrosomia defined as birth weight above
      4,000 g was used as outcome variable. The prevalence of clinical GDM and WHO 2013
      GDM was 0.4% (95% CI; 0-1.1) and 6.9% (95% CI; 4.5-9.2). WHO 2013 GDM, fasting
      blood glucose, pre-pregnant maternal overweight and obesity were associated with
      macrosomia. WHO 2013 GDM criteria were superior to clinical criteria in
      predicting macrosomia indicating that it may be time to consider the diagnostic
      strategy used in Greenland. Pre-pregnant overweight may also need more
      intensified lifestyle-intervention. ABBREVIATIONS: GDM: Gestational diabetes
      mellitus; VP: venous plasma; CWB: capillary whole blood; OGTT: oral glucose
      tolerance test; WHO: World Health Organisation; FIGO: The International
      Federation of Gynaecology and Obstetrics; BMI: body mass index; GA: gestational
      age.

PMID- 30300121
TI  - Escherichia coli mutation rates and spectra with combinations of environmental
      limitations.
AB  - Micro-organisms often face multiple stresses in natural habitats. Individual
      stresses are well known to influence mutation rates and the spectra of mutational
      types, but the extent to which multiple stresses affect the genetic variation in
      populations is unknown. Here we investigate pair-wise combinations of nutritional
      stresses in Escherichia coli to determine their effect on mutation rates and
      mutational types. Environmental interactions modified both the rate and spectrum
      of mutations in double-limited environments, but the effects were not additive or
      synergistic relative to single stresses. Generally, bacteria in the mixed
      environments behaved as if one of the two single-stress stimuli was more dominant
      and the genetic variation seen with every dual limitation was intermediate
      between known patterns with individual stresses. The composition of mutational
      types with double stresses was also intermediate between individual stress
      patterns. At least with mutations, the single stressor results available are
      reasonable indicators of stress-induced genetic variation in multifaceted natural
      habitats. With the influence of 11 conditions available on mutational patterns,
      we can now also see the clustering of mutational types as a function of these
      environments.

PMID- 30300120
TI  - Rubrobacter indicoceani sp. nov., a new marine actinobacterium isolated from
      Indian Ocean sediment.
AB  - A novel mesophilic marine actinobacterial strain, designated as SCSIO 08198T, was
      isolated from a deep-sea sediment sample collected from the Indian Ocean. The
      strain was Gram-stain-positive, rod-shaped and salmon pink in colour. Good growth
      occurred on marine agar with 1-5 % (w/v) NaCl and incubation at 28  degrees C for
      more than a fortnight. Sensitive to short ultraviolet radiation. Analysis of 16S
      rRNA gene sequences revealed that strain SCSIO 08198T had the highest similarity
      of 97.2 % to Rubrobacter radiotolerans DSM 5868T, and loosely related (<94.2 %)
      to all other species in the genus Rubrobacter. Phylogenetic analysis based on
      nearly complete 16S rRNA gene sequences revealed that the novel isolate shared a
      lineage with members of the genus Rubrobacter. The total cellular fatty acid
      profile was dominated by C16 : 0 12-methyl. MK-8 was the main menaquinone. The
      peptidoglycan type was A3alpha (l-Lys-l-Ala). The major phospholipids were
      diphosphatidylglycerol, phosphatidylglycerol and unidentified phospholipids.
      Based on the whole genome sequence analysis, the genome size is 3 078 689 bp with
      DNA G+C value of 63.8 mol%, including one circular chromosome and two plasmids.
      Based on these polyphasic data, a new species, Rubrobacterindicoceani sp. nov.,
      is proposed, with the type strain SCSIO 08198T (=DSM 105148T=CGMCC 1.16398T).

PMID- 30300122
TI  - Anti-Pseudomonas activity of 3-nitro-4-phenylfuroxan.
AB  - Pseudomonas aeruginosa is a microorganism that is well adapted to both clinical
      and industrial settings, where it can form adherent communities that are
      difficult to eradicate. New anti-Pseudomonas compounds and strategies are
      necessary, as the current antimicrobial approaches for the inhibition of biofilm
      formation and, above all, the eradication of formed biofilms are ineffective.
      Compounds that belong to the furoxan family, which are well-known NO donors, have
      recently been shown to display anti-Pseudomonas activity. The present study
      investigates three furoxan compounds that are substituted at the hetero-ring with
      electron-withdrawing groups (NO2, CN, CONH2) for their effects on P. aeruginosa
      PAO1 growth and biofilm formation/dispersal. Of the furoxans tested, only 3-nitro
      4-phenylfuroxan (KN455) inhibited the growth of suspended P. aeruginosa PAO1
      cultures. Furthermore, KN455 inhibited the formation of both younger and older
      biofilms with very high yields and thus proved itself to be toxic to planktonic
      subpopulations. It also displayed moderate eradicating power. The activity of
      KN455 does not appear to be related to its capacity to release small amounts of
      NO. Interestingly, the isomer 4-nitro-3-phenylfuroxan (KN454), included for
      comparison, displayed a comparable antibiofilm rate, but did not show the same
      antimicrobial activity against suspended cells and planktonic subpopulations.
      While hypotheses as to the mechanism of action have been formulated, further
      investigations are necessary to shed light onto the antimicrobial activity of
      this furoxan.

PMID- 30300123
TI  - Description of a novel species of fast growing mycobacterium: Mycobacterium
      kyogaense sp. nov., a scotochromogenic strain received as Mycobacterium vaccae.
AB  - A polyphasic study was undertaken to determine the taxonomic status of a rapidly
      growing, scotochromogenic organism that had been received as Mycobacterium
      vaccaeNCTC 11659T. The organism was found to have chemotaxonomic and cultural
      properties in accord with its assignment to the genus Mycobacteriumand was
      distinguished from the type strain of Mycobacterium vaccaeand from other closely
      related reference strains on the basis of concatenated sequences of 16S rRNA,
      gyrB, hsp65, recA and rpoB genes. It was also distinguished from M. vaccaestrain
      DSM 43292T and from the type strain of Mycobacterium obuense, its nearest
      phylogenetic neighbour, on the basis of chemotaxonomic and phenotypic data and
      digital DNA -DNA relatedness values of 22.7 and 68.3 %, respectively. These
      datasets not only indicate that strain NCTC 11659T had been misclassified as M.
      vaccae but that it merits recognition as representing a novel species of the
      genus Mycobacterium. It is proposed that the organism be classified as
      Mycobacteriumkyogaense sp. nov.

PMID- 30300124
TI  - Evaluation of sexual function in women with labia minora hypertrophy: A
      preliminary study.
AB  - OBJECTIVE: To compare the sexual functions in women with labia minora hypertrophy
      and age-matched healthy controls. MATERIAL AND METHOD: 43 patients with labia
      minora hypertrophy and 30 age-matched healthy controls were enrolled in the
      present study. The sexual functions of the women were evaluated by using the
      index of female sexual function (IFSF). RESULTS: Mean ages of the patients and
      controls were 30.06+/-7.11 and 31.34+/-4.12 (p=0.41), respectively. Mean total
      IFSF scores of the patients and controls were 24.18+/-3.24 and 27.53+/-4.43
      (p<0.05), respectively. The subscale scores of IFSF-lubrication, orgasm,
      satisfaction and pain in the patient group were significantly lower than in the
      control group (respectively, p<0.001, p<0.05, p<0.001 and p<0.05). There was no
      statistically significant difference between IFSF-arousal scores of the patient
      and control groups (p=0.30). The mean IFSF-desire scores of the patient group was
      higher than the controls (p<0.001). Labia minora hypertrophy was significantly
      associated with female sexual dysfunction (odds ratio [OR]=14.97, 95% confidence
      interval [Cl]=[3.66-61.21], p<0.001). CONCLUSION: This study suggests that
      patients with labia minora hypertrophy have poorer lubrication, satisfaction,
      pain, and orgasm scores on the IFSF scale compared to age-matched healthy
      controls.

PMID- 30300125
TI  - Association of open field behavior with blood and semen characteristics in
      roosters: an alternative animal model.
AB  - INTRODUCTION: The paucity of literature is addressed regarding the correlation
      between open field as an individual behavioral trait on reproductive capacity in
      animals. MATERIALS AND METHODS: To address this, Nine-month-old indigenous
      roosters were housed in individual cages. Each animal was observed twice a week
      for ten minutes before feeding in an open field apparatus for two weeks (7:00
      12:00PM). RESULTS: Interestingly, it was found that rooster's semen
      characteristics were correlated with their open field behavior. On the other
      hand, plasma glucose level as a blood attribute was more correlated with semen
      characteristics. The open field monitoring also revealed that the roosters with
      the lowest delay to their first pace had the highest sperm forward motility and
      lower sperm abnormality. The heterophil to lymphocyte ratio (H:L) was found to be
      low when pace bout and pace numbers were 20 and 35, respectively. The negative
      correlation between H:L ratio and semen characteristics (live sperm percentage,
      sperm concentration, and membrane integrity) may be an indication of poor
      reproductive performance in fearful roosters with higher H:L ratio. CONCLUSIONS:
      The data suggested a relationship between open field behavior indices and some
      reproductive parameters in roosters. The results might be applicable for
      selection of more reproductive animals. Hence, the rooster may also be useful
      model for similar studies in other species.

PMID- 30300126
TI  - [Transsexuality and the process of sexual reassignment from the perspective of
      male transsex: A qualitative study].
AB  - OBJECTIVE: To understand the process of sexual reassignment from the perspective
      of people who undergo this procedure; to know how their body image influences
      their day to day life and the impact on their sexuality, and to learn from
      transgender male experiences in order to guide the health care teams involved, so
      that they can provide care in a more adjusted way to actual needs. METHOD:
      Qualitative study with a total of 7 male transsexuals over 18 years of age,
      undergoing at least one surgery intervention for sexual reassignment, using data
      collection techniques such as individual, semi structured, open, audio recorded
      interviews and writing of reflective diaries. RESULTS: Decision making to undergo
      surgery to change their body image and sexual identity is complex. Factors
      influencing this decision are related to: the need to accept their own body, the
      experience with hormonal treatments, the relationship with the family and social
      context and with the partner, management of their own fears, the organization of
      health care services, the relationship and communication with the health care
      professionals, and the economic aspects. CONCLUSIONS: Both professionals and
      health services should consider and delve into the topic with the goal to
      understand the meaning of sex reassignment procedures to ensure better care for
      transsexualism.

PMID- 30300127
TI  - [Assessment of the erectile function and patients' perception of improvement in
      Spanish patients with erectile dysfunction].
AB  - OBJECTIVE: This study has been carried out to assess the hardness of erection and
      the perception of improvement in erectile function with the treatments received
      during the last month. MATERIAL AND METHOD: Descriptive, observational,
      multicenter, cross-sectional study carried out in 30 urology sites in Spain.
      Patients diagnosed of erectile dysfunction receiving treatment during at least
      the last month have been enrolled. Hardness of erection has been assessed with
      the erection hardness score and improvement perception has been estimated with
      the global assessment question. RESULTS: A 63% of patients had a hardness of
      erection that was insufficient for penetration, but 75% of patients referred that
      their erectile function had improved with treatment. After adjustment for other
      factors, erection hardness score values were not significantly different among
      patients being treated with alprostadil topical cream, compared to patients being
      treated with the combination of phosphodiesterase 5 (PDE5) inhibitors plus
      alprostadil topical cream or with PDE5i other than sildenafil alone. However,
      patients treated with alprostadil topical cream had a significantly higher chance
      of referring an improvement in their erectile function compared to patients
      treated with PDE5i, despite the fact that they had received treatment for a
      shorter period of time. CONCLUSION: Hardness of erection is just another factor
      of erectile function, but it is not the only one influencing improvement
      perception by patients.

PMID- 30300128
TI  - [Systematic review of the subjective experience of orgasm].
AB  - Orgasm is an essential component of the sexual response. Its study has generated
      results that point out its importance in human sexuality. The aim of the present
      study was to review the subjective orgasm experience, its evaluation and its
      association with personal, interpersonal and psychosocial variables. After
      conducting a literature search in major databases, we provide a total of 121
      scientific articles published between 2000 and 2016, in which the subjective
      orgasm experience was the main variable. The analysis of the related variables
      shows that personal variables (for example, health and demographic factors) and
      interpersonal variables (for example, sexual functioning) are the most
      considered. To conclude, we observe the need to develop standardized instruments
      to evaluate specifically the subjective orgasm experience and the need to study
      jointly the associated variables in order to propose explanatory models of orgasm
      that are useful for clinical practice.

PMID- 30300129
TI  - [Tunica albuginea adenomatoid tumor. A challenging case managed conservatively].
AB  - The adenomatoid tumors are rare benign mesothelial lesions that in males affect
      mainly the epididymis. They account for over one third of paratesticular tumors,
      and the treatment of choice has been surgical excision. The origin in testicular
      parenchyma or the tunica albuginea is extremely rare. Clinical signs and imaging
      studies are often inconclusive in differentiate from a more common malignant
      intratesticular solid tumour, which can result in unnecessary orchiectomies. We
      present a case of adenomatoid tumor of tunica albuginea where clinical suspicion
      and intraoperative frozen section analysis led to a partial orchiectomy.

PMID- 30300130
TI  - [Psychometric validation of the Portuguese version of the Massachusetts General
      Hospital - Sexual Functioning Questionnaire].
AB  - INTRODUCTION: Sexual dysfunctions are a high prevalence health problem, making it
      necessary to provide assessment instruments adapted to the Portuguese population.
      METHODS: The purpose of this study was to validate the Massachusetts General
      Hospital-Sexual Functioning Questionnaire (MGH-SFQ) for the Portuguese
      population. Participants in this study were 1079 Portuguese adults who completed
      a sociodemographic questionnaire and the MGH-SFQ. The participants' ages varied
      between 18 and 89 years of age (M = 29.66; SD = 13.05), and 32.6% (n = 352) were
      men and 67.4% (n = 727) were women. RESULTS: The Cronbach's alpha obtained was
      .91 and the psychometric properties of the scale were adequate. The validation of
      the construct was evaluated through Confirmatory Factor Analysis, setting up a
      suitable one-dimensional model (RMSEA = .041, CFI = .974). DISCUSSION: Taking
      into account the results of the psychometric validation, the sample size and the
      applicability of this instrument in clinical and sexological practice, we can
      confirm that this is a valid and reliable instrument to evaluate the sexual
      functioning of both Portuguese men and women.

PMID- 30300131
TI  - [Guide for the classification of clinical research articles for the International
      Journal of Andrology].
AB  - The classification of knowledge is essential for understanding between
      researchers and the advancement of science. In this article a brief
      classification of clinical research methods is presented. The advantages that
      researchers use the same nomenclature are recalled, which enables improved
      communication among researchers, facilitates replication of studies and searches
      in databases, and helps to establish the aspects that can affect the different
      research models. They are grouped into four broad categories: epidemiological
      articles, articles of qualitative methodology, mixed methodology articles and
      review articles.

PMID- 30300132
TI  - Long-term patient-reported satisfaction with different inflatable penile
      prosthesis: Comparison between AMS 700CX and Coloplast Titan.
AB  - INTRODUCTION: Erectile dysfunction (ED) is one of the most prevalent male sexual
      disorders worldwide. When conservative treatment is unsuccessful, contraindicated
      or causes unacceptable side effects penile prosthesis implantation is a
      definitive option for the management of ED. Although considered a third-line
      therapy, it achieves the highest satisfaction rates as compared with non-surgical
      treatment. Three-piece inflatable penile prothesis (IPP) represents the most
      sophisticated implantable device, AMS 700CXTM and Coloplast Titan(r) being the
      two most commonly used. Although there are several studies evaluating patient
      satisfaction with either model, there is little published data comparing both
      models. METHODS: We have compared overall patient satisfaction in 55 patients
      submitted to either 700CXTM or Titan(r) implantation. The Erectile Dysfunction
      Inventory of Treatment Satisfaction (EDITS) questionnaire was used to access
      patient satisfaction. RESULTS: Patient mean age and follow-up time were 59.1
      years and 57.9 months respectively. There was no difference in EDITS score
      between 700CXTM and Titan(r) IPP (77.2+/-12.1 versus 77.5+/-16.6 respectively,
      p=0.956). CONCLUSION: Overall patient satisfaction as assessed by EDITS
      questionnaire was not different between 700CXTM and Titan(r).

PMID- 30300133
TI  - Erectile dysfunction treated with intracavernous stem cells: A promising new
      therapy?
AB  - In the past decades, great interest has been shown in the development of new
      therapies for erectile dysfunction. Stem cell therapy has generated promising
      results in numerous preclinical trials in animal models, which is why has led to
      the development of the first clinical trials in humans. The main cause involved
      in the pathophysiology of erectile dysfunction is vascular damage related to
      endothelial and neuronal injury. The interest in stem cell therapy is justified
      by their capability to differentiate into specific damaged tissues, including
      endothelium and nervous tissue, and induction of the host own cell proliferation.
      Despite the great effort of the many studies carried out to date, knowledge about
      biological effects, therapeutic efficacy and safety of stem cells therapy for
      erectile dysfunction is still very limited.

PMID- 30300134
TI  - Testicular adrenal rest tumors.
AB  - We report a case of congenital adrenal hyperplasia in a 29 year old patient, who
      presented with testicular pain, bilateral testicular masses, and oligospermia.
      Ultrasonography confirmed, in both testis, the presence of heterogeneous and
      hypoechoic lesions with irregular borders and internal and peripheral
      vascularization. Seric tumor markers were negative. The patient was scheduled for
      perioperative testicular biopsy and bilateral orchiectomy. Perioperative biopsy
      was suggestive of testicular adrenal rest tumor and not additional procedure was
      performed. Treatment was initiated with high doses of glucocorticoids, decreasing
      the size of testicular masses and testicular pain was alleviated.

PMID- 30300135
TI  - Effect of anakinra, an interleukin one beta antagonist, on oxidative testicular
      damage induced in rats with ischemia reperfusion.
AB  - BACKGROUND: It has been reported in the literature that proinflammatory
      interleukin-1 beta (IL-1beta) is increased in cases of testicular ischemia
      reperfusion (I/R) damage. This information suggests that anakinra, an IL-1beta
      antagonist, may be effective in testicular I/R damage. OBJECTIVE: In our study,
      we investigated the effect of anakinra on testicular I/R damage induced in rats
      with torsion/detorsion. METHODS: The 50mg/kg anakinra+testicular
      torsion/detorsion (KTD-50) and 100mg/kg anakinra+testicular torsion/detorsion
      (KTD-100) groups received an intraperitoneal (i.p.) injection of 50mg/kg and
      100mg/kg of anakinra, respectively. In turn, the testicular torsion/detorsion
      (TTD) and sham operation (SOG) groups received a single dose of distilled water
      as a solvent 1h before ketamine anaesthesia. After the testes of the TTD, KTD-50
      and KTD-100 groups were subjected to torsion and detorsion for 4h each, the rats
      were killed with a high-dose anaesthesia, and their testicles were removed and
      evaluated through biochemical, gene expression and histopathological
      examinations. The results were evaluated in comparison with those of the SOG
      group. RESULTS: The levels of malondialdehyde (MDA), myeloperoxidase (MPO) and IL
      1beta showed significant increases in the TTD group, which underwent
      torsion/detorsion, compared to the KTD-50, KTD-100 and SOG groups. Conversely,
      the levels of glutathione (tGSH), glutathione peroxidase (GPO) and glutathione s
      transferase (GST) were found to be significantly higher in the KTD-50, KTD-100
      and SOG groups than in the TTD group. CONCLUSION: Anakinra at a 100mg/kg dose
      histologically suppressed better oxidative stress and tunica albuginea, germ
      cell, seminiferous tubule and interstitial damage in the testicular tissue
      compared to a 50mg/kg dose. Experimental results indicate that anakinra might be
      beneficial in the attenuation of testicular I/R damage.

PMID- 30300137
TI  - A Novel Insight into the Challenges of Diagnosing Degenerative Cervical
      Myelopathy using Online Symptom Checkers.
AB  - BACKGROUND: Degenerative Cervical Myelopathy (DCM) is a common debilitating
      condition resulting from degeneration of the cervical spine. Whilst decompressive
      surgery can halt disease progression, existing spinal cord damage is often
      permanent, leaving patients with lifelong disability. Early surgery improves the
      likelihood of recovery, yet the average time from onset of symptoms to correct
      diagnosis is over 2 years. The majority of delays occur initially, before and
      within primary care, mainly due to a lack of recognition. Symptom checkers are
      widely used by patients before medical consultation and can be useful for
      preliminary triage and diagnosis. Lack of recognition of DCM by symptom checkers
      may contribute to the delay in diagnosis. OBJECTIVE: The present study sought to
      investigate whether online symptom checkers are able to recognise relevant
      symptoms of DCM, to characterise the DCM differential returned, and to evaluate
      the diagnostic performance of its recognised symptoms. METHODS: Classical DCM
      symptoms were pooled from leading review articles. These symptoms were entered
      into the algorithms used by the top 20 symptom checker websites (N=4) (Google
      Search). The most widely cited symptom checker, WebMD, was used to characterise
      the differential diagnosis for DCM symptoms. RESULTS: 31 classical DCM symptoms
      were identified, of which 14 (45%) listed DCM as a differential and 3 (10%)
      placed DCM in the top third of the differential. The mean differential rank for
      motor symptoms was significantly better than for arthritic symptoms (P = .0093)
      and the average differential rank for all symptoms (P = .048). The symptom
      checker WebMD performed best at recognising DCM, placing it nearer the top of the
      differential list (average rank of 5.6) than both Healthline (rank of 12.9, P =
      .015) and Healthtools.AARP (rank of 15.5, P = .0014). On WebMD, only one
      combination of symptoms resulted in DCM as the primary differential: neck,
      shoulder and arm pain with hand weakness. 151 differential diagnoses for DCM
      symptoms were recorded on WebMD. Multiple sclerosis and peripheral neuropathy
      were the most common differentials, shortlisted for 52% and 32% of DCM symptoms
      respectively. CONCLUSIONS: DCM symptoms perform poorly in online symptom checkers
      and lead to a large differential of many other common conditions. Whilst a
      diagnosis becomes more likely as the number of symptoms increases, this will not
      support much needed earlier diagnosis. Symptom checkers remain an attractive
      concept with potential. Further research is required to support their
      optimisation.

PMID- 30300136
TI  - [Sexual life quality of spinal cord-injured men receiving pharmacological
      treatment for erectile dysfunction and their partners].
AB  - OBJECTIVE: To assess the quality of sexual life reported by spinal cord-injured
      men treated with oral drugs for erectile dysfunction (ED) and their female
      partners. MATERIAL AND METHOD: Men with spinal cord injuries (SCI) complaining of
      ED and their female partners were evaluated using the Sexual Life Quality
      Questionnaire (SLQQ), a fully validated instrument in Spain. Two studies were
      conducted. A transversal study (1) on patients who were already on treatment with
      phosphodiesterase type 5 inhibitors (PDE5Is) and their partners, with 73 couples
      providing valid data. An additional prospective study (2) assessed SCI patients
      naive to PDE5Is in which both the patients and their spouses answered the SLQQ
      before treatment and after 3 months taking PDE5Is regularly, with 12 couples
      completing the study. RESULTS: The SLQQ scores of SC injured men on PDE5Is (study
      1) were under the remembered pre-lesion level, with lower scores reported by
      those with complete lesions (P<.2 vs incomplete). Their partners' SLQQ scores
      were apparently similar to pre-injury times. The SLQQ scores of the patients and
      their partners were well correlated (r = 0.57, P<.0001), and they both reported
      high treatment satisfaction. Study 2: Untreated SCI patients reported very low
      SLQQ scores that were improved by PDE5Is treatment (P<.004), albeit without
      reaching the pre-injury level. A similar trend was found in their partners. Again
      both patients and partners reported high treatment satisfaction scores (P <.001).
      CONCLUSION: The sexual life quality levels of SC injured men on PDE5Is and their
      able-bodied spouses are well correlated. Both partners report high treatment
      satisfaction scores.

PMID- 30300138
TI  - Correction: Repeated superovulation increases the risk of osteoporosis and
      cardiovascular diseases by accelerating ovarian aging in mice.

PMID- 30300139
TI  - Correction: SIRT4 interacts with OPA1 and regulates mitochondrial quality control
      and mitophagy.

PMID- 30300140
TI  - Galpha12 ablation exacerbates liver steatosis and obesity by suppressing
      USP22/SIRT1-regulated mitochondrial respiration.
AB  - Nonalcoholic fatty liver disease (NAFLD) arises from mitochondrial dysfunction
      under sustained imbalance between energy intake and expenditure, but the
      underlying mechanisms controlling mitochondrial respiration have not been
      entirely understood. Heterotrimeric G proteins converge with activated GPCRs to
      modulate cell-signaling pathways to maintain metabolic homeostasis. Here, we
      investigated the regulatory role of G protein alpha12 (Galpha12) on hepatic lipid
      metabolism and whole-body energy expenditure in mice. Fasting increased Galpha12
      levels in mouse liver. Galpha12 ablation markedly augmented fasting-induced
      hepatic fat accumulation. cDNA microarray analysis from Gna12-KO liver revealed
      that the Galpha12-signaling pathway regulated sirtuin 1 (SIRT1) and PPARalpha,
      which are responsible for mitochondrial respiration. Defective induction of SIRT1
      upon fasting was observed in the liver of Gna12-KO mice, which was reversed by
      lentivirus-mediated Galpha12 overexpression in hepatocytes. Mechanistically,
      Galpha12 stabilized SIRT1 protein through transcriptional induction of ubiquitin
      specific peptidase 22 (USP22) via HIF-1alpha increase. Galpha12 levels were
      markedly diminished in liver biopsies from NAFLD patients. Consistently, Gna12-KO
      mice fed a high-fat diet displayed greater susceptibility to diet-induced liver
      steatosis and obesity due to decrease in energy expenditure. Our results
      demonstrate that Galpha12 regulates SIRT1-dependent mitochondrial respiration
      through HIF-1alpha-dependent USP22 induction, identifying Galpha12 as an upstream
      molecule that contributes to the regulation of mitochondrial energy expenditure.

PMID- 30300141
TI  - Bone marrow transplantation generates T cell-dependent control of myeloma in
      mice.
AB  - Transplantation with autologous hematopoietic progenitors remains an important
      consolidation treatment for patients with multiple myeloma (MM) and is thought to
      prolong the disease plateau phase by providing intensive cytoreduction. However,
      transplantation induces inflammation in the context of profound lymphodepletion
      that may cause hitherto unexpected immunological effects. We developed
      preclinical models of bone marrow transplantation (BMT) for MM using Vk*MYC
      myeloma-bearing recipient mice and donor mice that were myeloma naive or myeloma
      experienced to simulate autologous transplantation. Surprisingly, we demonstrated
      broad induction of T cell-dependent myeloma control, most efficiently from memory
      T cells within myeloma-experienced grafts, but also through priming of naive T
      cells after BMT. CD8+ T cells from mice with controlled myeloma had a distinct T
      cell receptor (TCR) repertoire and higher clonotype overlap relative to myeloma
      free BMT recipients. Furthermore, T cell-dependent myeloma control could be
      adoptively transferred to secondary recipients and was myeloma cell clone
      specific. Interestingly, donor-derived IL-17A acted directly on myeloma cells
      expressing the IL-17 receptor to induce a transcriptional landscape that promoted
      tumor growth and immune escape. Conversely, donor IFN-gamma secretion and
      signaling were critical to protective immunity and were profoundly augmented by
      CD137 agonists. These data provide new insights into the mechanisms of action of
      transplantation in myeloma and provide rational approaches to improving clinical
      outcomes.

PMID- 30300142
TI  - Temporal dynamics of Wnt-dependent transcriptome reveal an oncogenic
      Wnt/MYC/ribosome axis.
AB  - Activating mutations in the Wnt pathway drive a variety of cancers, but the
      specific targets and pathways activated by Wnt ligands are not fully understood.
      To bridge this knowledge gap, we performed a comprehensive time-course analysis
      of Wnt-dependent signaling pathways in an orthotopic model of Wnt-addicted
      pancreatic cancer, using a porcupine (PORCN) inhibitor currently in clinical
      trials, and validated key results in additional Wnt-addicted models. The temporal
      analysis of the drug-perturbed transcriptome demonstrated direct and indirect
      regulation of more than 3,500 Wnt-activated genes (23% of the transcriptome).
      Regulation was both via Wnt/beta-catenin and through the modulation of protein
      abundance of important transcription factors, including MYC, via Wnt-dependent
      stabilization of proteins (Wnt/STOP). Our study identifies a central role of
      Wnt/beta-catenin and Wnt/STOP signaling in controlling ribosome biogenesis, a key
      driver of cancer proliferation.

PMID- 30300144
TI  - Ultrasound-Guided Cubital Tunnel Decompression in a Collegiate Swimmer: A Case
      Report.
AB  - A 19-year-old female collegiate swimmer presented to our sports medicine clinic
      with a history and physical examination consistent with right ulnar neuropathy at
      the cubital tunnel. Diagnostic ultrasound (US) revealed compression of the ulnar
      nerve under the cubital tunnel retinaculum (CTR) with nerve swelling proximal to
      the site of compression. Electrodiagnostic studies confirmed the diagnosis of a
      moderate to severe ulnar neuropathy at the elbow. Treatment consisted of an US
      guided decompression of the ulnar nerve in the cubital tunnel by cutting the CTR
      using a rotated stylet "v" cutting technique. The patient's symptoms resolved,
      and she was able to begin a swimming progression 2 weeks after the procedure.
      After completion of this progression, she was able to successfully resume full,
      unrestricted competitive collegiate swimming without return of her symptoms. To
      the best of our knowledge, this is the first description of an US-guided cubital
      tunnel decompression surgery.

PMID- 30300143
TI  - Concussion Burden, Recovery, and Risk Factors in Elite Youth Ice Hockey Players.
AB  - OBJECTIVE: To examine rates of concussion and more severe concussion (time loss
      of greater than 10 days) in elite 13- to 17-year-old ice hockey players. METHODS:
      This is a prospective cohort study (Alberta, Canada). Bantam (13-14 years) and
      Midget (15-17 years) male and female elite (top 20% by division of play) youth
      ice hockey players participated in this study. Players completed a demographic
      and medical history questionnaire and clinical test battery at the beginning of
      the season. A previously validated injury surveillance system was used to
      document exposure hours and injury during one season of play (8 months). Players
      with a suspected ice hockey-related concussion were referred to the study sport
      medicine physicians for assessment. Time loss from hockey participation was
      documented on an injury report form. RESULTS: Overall, 778 elite youth ice hockey
      players (659 males and 119 females; aged 13-17 years) participated in this study.
      In total, 143 concussions were reported. The concussion incidence rate (IR) was
      17.60 concussions/100 players (95% CI, 15.09-20.44). The concussion IR was 1.31
      concussions/1000 player-hours (95% CI, 1.09-1.57). Time loss of greater than 10
      days was reported in 74% of cases (106/143), and 20% (n = 28) had time loss of
      greater than 30 days. CONCLUSIONS: Concussion is a common injury in elite youth
      ice hockey players. In this study population, a large proportion of concussions
      (74%) resulted in a time loss of greater than 10 days, possibly reflecting more
      conservative management or longer recovery in youth athletes.

PMID- 30300145
TI  - Selected Case From the Arkadi M. Rywlin International Pathology Slide Seminar:
      Atypical Thymoma With Rhabdomyomatous Differentiation.
AB  - Thymic epithelial neoplasms with foci of rhabdomyomatous differentiation are
      rare. A case is presented of a primary thymic epithelial neoplasm showing the
      features of an atypical spindle cell thymoma that contained foci of bland
      appearing rhabdomyomatous cells. The histologic and immunohistochemical features
      of this tumor are discussed along with a review of the literature and the
      comments from the AMR members to the case.

PMID- 30300147
TI  - Gleason Grading: There is No Substitute for Judgment.

PMID- 30300146
TI  - Gleason Grading: Clear and Straightforward Rules Facilitate Judgment.

PMID- 30300148
TI  - Low-dose, short course alteplase treatment of submassive pulmonary embolism: a
      case series from the National Institutes of Health Clinical Center.
AB  - : Guidelines-recommend thrombolytic therapy for pulmonary embolism in patients
      with severe hemodynamic compromise and low risk of bleeding. Thrombolytics in
      submassive pulmonary embolism have an unfavorable risk/benefit ratio and remain
      controversial. Based on our experience with extensive, lower extremity thrombi,
      nine patients with symptomatic, submassive pulmonary embolisms (five medical,
      four surgical) were treated with low-dose alteplase (<10 mg/day, infused over 6 h
      per treatment). Alteplase was delivered by pulse spray and/or directed or
      undirected central venous catheters depending on clot size and location. All
      patients improved symptomatically and as determined objectively by pulmonary
      artery pressures and/or imaging, though acute benefits ranged from substantial to
      modest. One surgical patient required re-exploration for bleeding at the site of
      a recent retroperitoneal lymph node dissection. This experience may help guide
      the design of a randomized controlled trial to determine the safety and efficacy
      of low-dose alteplase for submassive pulmonary embolism.

PMID- 30300149
TI  - Fatal pulmonary embolism and pulmonary hemorrhage in lupus anticoagulant
      hypoprothrombinemia syndrome: a case report and review of literature.
AB  - : Lupus anticoagulant hypoprothrombinemia syndrome (LAHS) is a rare disorder
      characterized by development of lupus anticoagulant and antiprothrombin
      antibodies. The most common clinical manifestation is bleeding. Clinical
      management can be challenging due to the subtle balance between the bleeding and
      thrombotic tendencies. We report a novel case of LAHS in which the patient
      experienced the sequence of hemorrhage-thrombosis-hemorrhage before eventually
      dying of fatal pulmonary embolism and pulmonary hemorrhage. Specifically, she
      presented with multiple gastrointestinal bleeding episodes, followed by
      multifocal subdural hematomas, pulmonary embolism after normalization of
      prothrombin activity levels with immunosuppression, and finally with fatal
      pulmonary hemorrhage after enoxaparin treatment for pulmonary embolism. This case
      illustrates the importance of recognizing early minor bleeding episodes, and
      detecting specific antiprothrombin antibodies, in the diagnosis of LAHS.
      Furthermore, it highlights the complex challenge of normalizing prothrombin
      activity levels while at the same time preventing medical complications.

PMID- 30300150
TI  - Predictors of reliably high-value end-of-life care.
AB  - PURPOSE OF REVIEW: Care near the end of life is expensive and frequently not
      aligned with the expressed preferences of decedents, creating an opportunity to
      improve value, or increase quality while lowering cost. This review examines
      publications from 2017 and 2018 on interventions and policies associated with
      high-value end-of-life care. Innovations in video and web-based advance care
      planning are promising to improve preference-congruent care at low cost. RECENT
      FINDINGS: The patterns of care within hospice and in particular increased
      investment in patient care in hospice are shown to improve value. A meta-analysis
      demonstrated the role of inpatient palliative care consultations in decreasing
      hospitalization costs, as did several studies on inpatient palliative care units.
      Internationally, a range of home-based palliative care programs, implemented at
      the population level, demonstrated cost savings and reduced intensive care near
      the end of life. Finally, public policies that funded medical and long-term care
      and address broader inequalities were demonstrated to decrease low-value care
      near the end of life. SUMMARY: This review demonstrates the efficacy of a range
      of approaches to improve value of care at the end of life, both within the health
      system and across public policy sectors.

PMID- 30300151
TI  - Technology for improving accessibility of end-of-life care: Extension for
      Community Healthcare Outcomes Project.
AB  - PURPOSE OF REVIEW: To describe how Project ECHO works and to analyze what has
      been published on Project ECHO Palliative Care (Project ECHO PC) over the last 18
      months. RECENT FINDINGS: Only two articles on Project ECHO PC have been published
      over the last 18 months: a descriptive study of experiences in seven health
      centers of the United States, the United Kingdom, Uruguay and India; and a
      quantitative and qualitative study of the impact of the teleECHO clinic on
      physicians and nurses in Northern Ireland, which reports a significant boost in
      knowledge acquisition and self-efficacy. SUMMARY: Project ECHO is an innovative
      telemedicine strategy, which creates learning communities, which use a
      standardized methodology and benefits healthcare professionals, particularly
      primary care providers or practitioners based on remote or rural areas.Since
      2011, Project ECHO PC has been implemented in 12 health centers in 4 different
      countries, with greater growth in 2017. It has facilitated a wider access to
      professional education, improvements in clinical practice and knowledge
      acquisition, the development of professional curricula and more confidence and
      self-efficacy among healthcare professionals. Project ECHO PC is engaged in
      several international initiatives to aid countries with different degrees of
      palliative care development.

PMID- 30300152
TI  - Compassion in palliative care: a review.
AB  - PURPOSE OF REVIEW: Compassion has been recognized as a key aspect of high-quality
      healthcare, particularly in palliative care. This article provides a general
      review of the current understanding of compassion in palliative care and
      summarizes emergent compassionate initiatives in palliative care at three
      interdependent levels: compassion for patients, compassion in healthcare
      professionals, and compassionate communities at the end of life. RECENT FINDINGS:
      Compassion is a constructive response to suffering that enhances treatment
      outcomes, fosters the dignity of the recipient, and provides self-care for the
      giver. Patients and healthcare professionals value compassion and perceive a
      general lack of compassion in healthcare systems. Compassion for patients and for
      professionals' self-care can be trained and implemented top-down (institutional
      policies) and bottom-up (compassion training). 'Compassionate communities' is an
      important emerging movement that complements regular healthcare and social
      services with a community-level approach to offer compassionate care for people
      at the end of life. SUMMARY: Compassion can be enhanced through diverse
      methodologies at the organizational, professional, and community levels. This
      enhancement of compassion has the potential to improve quality of palliative care
      treatments, enhance healthcare providers' satisfaction, and reduce healthcare
      costs.

PMID- 30300153
TI  - Palliative care teaching shapes medical undergraduate students' professional
      development: a scoping review.
AB  - PURPOSE OF REVIEW: The aim of this review is to understand how palliative care
      teaching (PCT) as a patient-centered learning model, influences medical
      undergraduate students' professional development. RECENT FINDINGS: To study PCT
      medical undergraduate students' learning experiences, we have employed the
      medical teaching concept, 'hidden curriculum,' as a way of describing attitudes
      and behavior conveyed implicitly by palliative care educators. Fifteen studies
      were selected: ten of those studies used a qualitative approach; two are
      theoretical explanations of the topic explored, one guideline, one review and
      just one quantitative study, made up the review. Medical undergraduate students
      reported that after PCT, they felt they had acquired better attitudes for
      effective integration with the patient, such as empathy or holistic care; ethical
      principles, such as respect or humanization of their clinical practice; and
      commitment to an improvement in competences, such as self-awareness or self
      esteem. They also reported improved behavior in effective integration with
      patients, such as communication, caring for patients' families, and when
      addressing psychosocial, cultural and spiritual aspects; their commitment to
      improvement in competences, such as dealing with emotions and uncertainty; they
      learned team work as an effective way to interact within the health system; and
      to become more reliable, making themselves more available and dedicating enough
      time to each patient. SUMMARY: PCT seems to be an effective way of fostering
      medical undergraduate students' patient-centered professional development.

PMID- 30300154
TI  - The role of day care in supporting older people living with long-term conditions.
AB  - PURPOSE OF REVIEW: For older people with long-term conditions, regular structured
      activities within a community setting meeting others are thought to improve well
      being and quality of life. Historically local authority-run day care centres were
      widely available, but austerity measures have meant that in many areas, such
      provision has been markedly reduced and different models of day care services are
      being developed. There is little known about outcomes of day care provision for
      older people with long-term conditions. RECENT FINDINGS: This review has
      critically examined the recent evidence on outcomes of day care provision for
      older people with long-term conditions and will focus on three areas - physical
      functioning, intergenerational provision and measurement of outcomes. In terms of
      interventions to improve physical functioning for older people with long-term
      conditions attending day care, there are few studies and it is difficult to
      generalize but there appears to be a trend for positive impact on physical
      functioning when activities are incorporated into a day care programme. There is
      a paucity of research on intergenerational provision, however, the small number
      of studies suggest positive benefits. Studies measuring outcomes for older people
      with long-term conditions attending day care services are very limited in terms
      of outcome data with the exception of a Canadian study, which suggested that
      attendance at day care could reduce hospital attendance and admissions. SUMMARY:
      This review reveals a lack of research of day care provision for older people
      with long-term conditions. There is a suggestion in the small number of articles
      included in this review that there can be benefits both in terms of global
      outcomes of attendance and in improved physical functioning; there is limited
      evidence of the value of intergenerational provision. Robust research with
      collection of meaningful outcomes is required to ensure that the increasing
      number of older people with long-term conditions are enabled to access high
      quality day care provision.

PMID- 30300155
TI  - Targeting IL-1alpha in cancer cachexia: a narrative review.
AB  - PURPOSE OF REVIEW: Cachexia is defined as ongoing loss of skeletal muscle mass,
      with or without depletion of adipose tissue and is a common syndrome in cancer
      patients, affecting 50% of those diagnosed. Cachexia, which cannot be fully
      reversed and causes significant functional impairment is caused by various
      mechanisms such as an altered energy balance and disruption of homeostatic
      control by the central nervous system. This central nervous system deregulation
      involves hypothalamic pituitary adrenal (HPA) axis stimulation, which can be
      triggered by IL-1R1 engagement on neuronal processes and endothelium in the
      microvasculature of the hypothalamus. This review will explore current evidence
      regarding both the importance of IL-1alpha in the various components of cancer
      cachexia and its potential as a therapeutic target. RECENT FINDINGS: IL-1alpha,
      which signals through IL-1R1, has been identified as a key agonist in the IL-1
      pathway. As such, IL-1alpha has been explored as a therapeutic target in cancer
      cachexia, leading to the development of bermekimab, a mAb which neutralizes IL
      1alpha. With a limited array of medication currently available to treat cancer
      cachexia, bermekimab represents a possible therapy. SUMMARY: IL-1alpha is a key
      mediator in cachexia development and targeting this may be a viable therapeutic
      target.

PMID- 30300156
TI  - 'The shoulders, clavicles, chest and thighs melt away': a compilation of reviews
      on cachexia.

PMID- 30300157
TI  - Early Resumption of beta Blockers Is Associated with Decreased Atrial
      Fibrillation after Noncardiothoracic and Nonvascular Surgery: A Cohort Analysis.
AB  - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW:
      BACKGROUND:: Beta (beta) blockers reduce the risk of postoperative atrial
      fibrillation and should be restarted after surgery, but it remains unclear when
      best to resume beta blockers postoperatively. The authors thus evaluated the
      relationship between timing of resumption of beta blockers and atrial
      fibrillation in patients recovering from noncardiothoracic and nonvascular
      surgery. METHODS: The authors evaluated 8,201 adult beta-blocker users with no
      previous history of atrial fibrillation who stayed at least two nights after
      noncardiothoracic and nonvascular surgery as a retrospective observational
      cohort. After propensity score matching on baseline and intraoperative variables,
      1,924 patients who did resume beta blockers by the end of postoperative day 1
      were compared with 973 patients who had not resumed by that time on postoperative
      atrial fibrillation using logistic regression. A secondary matched analysis
      compared 3,198 patients who resumed beta blockers on the day of surgery with
      3,198 who resumed thereafter. RESULTS: Of propensity score-matched patients who
      resumed beta blockers by end of postoperative day 1, 4.9% (94 of 1,924) developed
      atrial fibrillation, compared with 7.0% (68 of 973) of those who resumed
      thereafter (adjusted odds ratio, 0.69; 95% CI, 0.50-0.95; P = 0.026). Patients
      who resumed beta blockers on day of surgery had an atrial fibrillation incidence
      of 4.9% versus 5.8% for those who started thereafter (odds ratio, 0.84; 95% CI,
      0.67-1.04; P = 0.104). CONCLUSIONS: Resuming beta blockers in chronic users by
      the end of the first postoperative day may be associated with lower odds of in
      hospital atrial fibrillation. However, there seems to be little advantage to
      restarting on the day of surgery itself.

PMID- 30300158
TI  - Achieved Gain and Subjective Outcomes for a Wide-Bandwidth Contact Hearing Aid
      Fitted Using CAM2.
AB  - OBJECTIVES: The objective of this study was to test the ability to achieve,
      maintain, and subjectively benefit from extended high-frequency amplification in
      a real-world use scenario, with a device that restores audibility for frequencies
      up to 10 kHz. DESIGN: A total of 78 participants (149 ears) with mild to
      moderately-severe sensorineural hearing loss completed one of two studies
      conducted across eight clinical sites. Participants were fitted with a light
      driven contact hearing aid (the Earlens system) that directly drives the tympanic
      membrane, allowing extended high-frequency output and amplification with minimal
      acoustic feedback. Cambridge Method for Loudness Equalization 2 - High Frequency
      (CAM2)-prescribed gains for experienced users were used for initial fitting, and
      adjustments were made when required according to participant preferences for
      loudness and comfort or when measures of functional gain (FG) indicated that more
      or less gain was needed. Participants wore the devices for an extended period.
      Prescribed versus adjusted output and gain, frequency-specific FG, and self
      perceived benefit assessed with the Abbreviated Profile of Hearing Aid Benefit,
      and a custom questionnaire were documented. Self-perceived benefit results were
      compared with those for unaided listening and to ratings with participants' own
      acoustic hearing aids. RESULTS: The prescribed low-level insertion gain from 6 to
      10 kHz averaged 53 dB across all ears, with a range from 26 to 86 dB. After
      adjustment, the gain from 6 to 10 kHz decreased to an average of 45 dB with a
      range from 16 to 86 dB. Measured FG averaged 39 dB from 6 to 10 kHz with a range
      from 11 to 62 dB. Abbreviated Profile of Hearing Aid Benefit results revealed a
      significant improvement in communication relative to unaided listening, averaging
      28 to 32 percentage points for the background noise, reverberation, and ease of
      communication subscales. Relative to participants' own hearing aids, the
      subscales ease of communication and aversiveness showed small but significant
      improvements for Earlens ranging from 6 to 7 percentage points. For the custom
      satisfaction questionnaire, most participants rated the Earlens system as better
      than their own hearing aids in most situations. CONCLUSIONS: Participants used
      and reported subjective benefit from the Earlens system. Most participants
      preferred slightly less gain at 6 to 10 kHz than prescribed for experienced users
      by CAM2, preferring similar gains to those prescribed for inexperienced users,
      but gains over the extended high frequencies were high relative to those that are
      currently available with acoustic hearing aids.This is an open access article
      distributed under the Creative Commons Attribution License 4.0 (CCBY), which
      permits unrestricted use, distribution, and reproduction in any medium, provided
      the original work is properly cited.

PMID- 30300159
TI  - Mesenchymal stromal cells in kidney transplantation.
AB  - PURPOSE OF REVIEW: Mesenchymal stromal cells (MSC) have emerged as one of the
      most promising candidates for immunomodulatory cell therapy in kidney
      transplantation. Here we describe novel insights into the MSC mechanism of action
      and provide an overview of initial safety and feasibility studies with MSC in
      kidney transplantation. RECENT FINDINGS: Clinical studies of MSC-based cell
      therapy in kidney transplant recipients demonstrated the safety and feasibility
      of cell therapy and provide the first encouraging evidence of the efficacy of MSC
      in enabling the minimization of immunosuppressive drugs. In our initial
      experience with MSC-based therapy in kidney transplant recipients we carried out
      extensive clinical and immunological monitoring of MSC-treated patients and found
      possible biomarkers of MSC immunomodulation in some of them. Based on these
      biomarkers we identified a patient in whom complete discontinuation of
      immunosuppression has been achieved safely and successfully. SUMMARY: Many issues
      should be addressed before MSC-based therapy becomes a standard treatment
      protocol for kidney transplantation. A better understanding of the MSC mechanism
      of action and the identification of biomarkers of response to therapy will inform
      the rational design of the most effective clinical protocol and the selection of
      patients amenable to safe immunosuppressive drug withdrawal.

PMID- 30300161
TI  - Fatal iatrogenic vinorelbine poisoning: a case report.
AB  - The paper describes the case of a 69-year-old man with non-small-cell lung cancer
      who, owing to a mistake, received intravenously 500 mg of vinorelbine. Within 3
      days of intoxication, the bone marrow of the patient was damaged with subsequent
      pancytopenia that did not respond to treatment. On the fifth day after the
      poisoning, features of intestinal obstruction appeared. The patient died on the
      sixth day after the drug overdose. The case presented by us constitutes the first
      description of a fatal iatrogenic poisoning with this drug.

PMID- 30300160
TI  - Prognosis of patients with gastric variceal bleeding after endoscopic variceal
      obturation according to the type of varices.
AB  - BACKGROUND AND AIMS: This study was performed to evaluate the treatment efficacy
      of endoscopic variceal obturation (EVO) in patients with gastric variceal
      bleeding (GVB) according to the type of varices. PATIENTS AND METHODS: All
      patients who were treated with EVO for bleeding from gastric varices (GVs) were
      included. Patients with a previous history of endoscopic treatment for GVB and
      those with accompanying portal vein invasion by hepatocellular carcinoma or other
      malignancy were excluded. RESULTS: Ninety-one patients with GVB were included.
      Mean age was 59.4+/-12.4 years and 72 (79.1%) patients were men. The types of
      varices were gastroesophageal varices (GOV) type 1 (GOV1), GOV2, and isolated
      gastric varices type 1 (IGV1) in 30 (33.3%), 35 (38.5%), and 26 (28.6%) patients,
      respectively. Hemostasis and GV obliteration were achieved in 88 (96.7%) and 81
      (89.0%) patients, respectively. Among 81 patients with GV obliteration, GV
      recurred in 26 (32.1%) patients. The GV recurrence rate was significantly lower
      in patients with GOV1 than in those with GOV2 (P=0.007), while it was comparable
      between patients with GOV1 and IGV1 (P=0.111) and between patients with GOV2 and
      IGV1 (P=0.278). Variceal rebleeding occurred in 11 (13.6%) patients. GVB
      recurrence rate was significantly higher in patients with GOV2 than in those with
      GOV1 (P=0.034) and IGV1 (P=0.018), while it was comparable between patients with
      GOV1 and IGV1 (P=0.623). Mortality rate was comparable among the three groups.
      CONCLUSIONS: EVO was very effective in patients with GVB. GV recurrence and GV
      rebleeding were significantly lower in patients with GOV1 than in those with
      GOV2.

PMID- 30300162
TI  - 2018 Frank Stinchfield Award: Spinopelvic Hypermobility Is Associated With an
      Inferior Outcome After THA: Examining the Effect of Spinal Arthrodesis.
AB  - BACKGROUND: Many patients undergo both THA and spinal arthrodesis, and those
      patients may not fare as well as those who undergo one procedure but not the
      other. The mechanisms of how spinal arthrodesis affects patient function after
      THA remain unclear. QUESTIONS/PURPOSES: The aims of our study were to (1)
      determine how patient-reported outcome measures (PROMs), including the Oxford hip
      score as well as dislocations and complications compare after THA between
      patients with and without spinal arthrodesis; (2) characterize sagittal pelvic
      changes in these patients that occur when moving between different functional
      positions and test for differences between patients with and without spinal
      arthrodesis; and (3) assess whether differences in sagittal pelvic dynamics are
      associated with PROMs, complications, and dislocations after THA. METHODS: In
      this case-control study, we identified 42 patients (60 hips) who had undergone
      both THA and spinal arthrodesis between 2002 and 2016 and who were available for
      followup at a minimum of 12 months (mean, 6 +/- 5 years) after the later of the
      two procedures. These cases were case-control-matched for age, gender, and body
      mass index with 42 patients (60 hips) who underwent only THA and had no known
      spinal pathology. All patients completed PROMs, including the Oxford hip score,
      and underwent four radiographs of the pelvis and spinopelvic complex in three
      positions (supine, standing, and deep-seated). Cup orientation and various
      spinopelvic parameters, including pelvic tilt and pelvic-femoral angle, were
      measured. The difference in pelvic tilt between standing and seated allowed for
      patient classification based on spinopelvic mobility into normal (+/- 10 degrees 
      30 degrees ), stiff (< +/- 10 degrees ) or hypermobile (> +/- 30 degrees )
      groups. RESULTS: Compared with the THA-only group, the THA-spinal arthrodesis
      group had inferior PROMs (Oxford hip score, 33 +/- 10 versus 43 +/- 6; p < 0.001)
      and more surgery-related complications (such as dislocation, loosening,
      periprosthetic fracture or infection, psoas irritation) (12 versus 3; p = 0.013),
      especially dislocation (5 versus 0; p = 0.023). We detected no difference in
      change of pelvic tilt between supine and standing positions between the groups.
      When standing, patients undergoing THA-spinal arthrodesis had greater pelvic tilt
      (25 degrees  +/- 11 degrees  versus 17 degrees  +/- 8 degrees ; p < 0.001) and
      the hip was more extended (193 degrees  +/- 22 degrees  versus 185 degrees  +/-
      30 degrees ; p = 0.012). We found that patients undergoing THA-spinal arthrodesis
      were more likely to have spinopelvic hypermobility (12 of 42 versus three of 42;
      odds ratio, 5.2; p = 0.02) with anterior tilting of the pelvis. Of all
      biomechanical parameters, only spinopelvic hypermobility was associated with
      inferior PROMs (Oxford hip score, 35 +/- 9 versus 40 +/- 7 in normal mobility; p
      = 0.049) and was also present in dislocating hips that underwent revision despite
      acceptable cup orientation. CONCLUSIONS: In patients with spinal arthrodesis who
      have undergone THA, spinopelvic hypermobility is associated with inferior
      outcomes, including hip instability. Spinopelvic hypermobility should be
      routinely assessed because these patients may have a narrow zone of optimum cup
      orientation that would require new technology to define and assist the surgeon in
      obtaining it.Level of Evidence Level III, therapeutic study.

PMID- 30300163
TI  - Postmortem Diagnosis of Myocardial Infarction Due to Butane Gas Intoxication in a
      Child: A Case Report.
AB  - Volatile substance addiction and toxic gas inhalation are now an important health
      problem. The pleasure-based inhalation of butane gas, also known as lighter
      refill gas, is especially prevalent among children and young people. The most
      important reasons for this situation are that they are cheap and easy to obtain
      and lack of legal supervision. The exhaled gas is absorbed through the alveolar
      surface and rapidly enters the bloodstream and leads to clinical signs. It can
      cause dizziness, nausea, vomiting, confusion, hallucinations, and euphoria in the
      acute phase. In severe cases, bronchospasm, hypoxia, ventricular arrhythmia,
      cardiopulmonary arrest, and death can occur. Our case is one of the rare cases in
      the literature that was diagnosed by postmortem histopathological examination.
      Our case is a 15-year-old girl who was found in front of a tobacco product store.
      On gross examination, there was a hemorrhagic area under the aortic valve that
      continued to interventricular septum. There was no coronary artery lesion.
      Histopathological examination revealed hypereosinophilia and contraction band
      necrosis in myocardial fibers, which was more intense in papillary muscle.
      Immunohistochemical studies also supported early myocardial ischemic changes.
      Upon toxicological examination, butane gas was detected in lung and blood
      samples.

PMID- 30300164
TI  - Linearity, Bias, Intrascanner Repeatability, and Interscanner Reproducibility of
      Quantitative Multidynamic Multiecho Sequence for Rapid Simultaneous Relaxometry
      at 3 T: A Validation Study With a Standardized Phantom and Healthy Controls.
AB  - OBJECTIVES: The aim of this study was to evaluate the linearity, bias,
      intrascanner repeatability, and interscanner reproducibility of quantitative
      values derived from a multidynamic multiecho (MDME) sequence for rapid
      simultaneous relaxometry. MATERIALS AND METHODS: The NIST/ISMRM (National
      Institute of Standards and Technology/International Society for Magnetic
      Resonance in Medicine) phantom, containing spheres with standardized T1 and T2
      relaxation times and proton density (PD), and 10 healthy volunteers, were scanned
      10 times on different days and 2 times during the same session, using the MDME
      sequence, on three 3 T scanners from different vendors. For healthy volunteers,
      brain volumetry and myelin estimation were performed based on the measured T1,
      T2, and PD. The measured phantom values were compared with reference values;
      volunteer values were compared with their averages across 3 scanners. RESULTS:
      The linearity of both phantom and volunteer measurements in T1, T2, and PD values
      was very strong (R = 0.973-1.000, 0.979-1.000, and 0.982-0.999, respectively) The
      highest intrascanner coefficients of variation (CVs) for T1, T2, and PD were
      2.07%, 7.60%, and 12.86% for phantom data, and 1.33%, 0.89%, and 0.77% for
      volunteer data, respectively. The highest interscanner CVs of T1, T2, and PD were
      10.86%, 15.27%, and 9.95% for phantom data, and 3.15%, 5.76%, and 3.21% for
      volunteer data, respectively. Variation of T1 and T2 tended to be larger at
      higher values outside the range of those typically observed in brain tissue. The
      highest intrascanner and interscanner CVs for brain tissue volumetry were 2.50%
      and 5.74%, respectively, for cerebrospinal fluid. CONCLUSIONS: Quantitative
      values derived from the MDME sequence are overall robust for brain relaxometry
      and volumetry on 3 T scanners from different vendors. Caution is warranted when
      applying MDME sequence on anatomies with relaxometry values outside the range of
      those typically observed in brain tissue.

PMID- 30300165
TI  - Markers of mineralocorticoid receptor function: changes over time and
      relationship to response in patients with major depression.
AB  - The renin-angiotensin-aldosterone system and its hormone receptors, i.e. the
      angiotensin and mineralocorticoid receptor (MR), have emerged as important
      targets for central nervous system disorders and in particular for major
      depression. We have recently characterized baseline MR function as a predictor
      for treatment outcome with standard antidepressants. The aims of this study are
      (i) to characterize how strongly an early biomarker change (after 2 weeks) is
      related to outcome and (ii) whether these biomarker changes are related to the
      final outcome, that is, could serve as surrogate markers for response. Twenty
      four of 30 patients with unipolar major depression completed the observational
      trial. MR-related biomarkers were assessed at baseline, 2 weeks, and 6 weeks of
      standard antidepressant treatment. These biomarkers included slow wave sleep
      (SWS), salivary cortisol and aldosterone after awakening, heart rate variability
      measured as respiratory sinus arrhythmia (RSA), systolic blood pressure, salt
      taste intensity (STI), salt pleasantness (SP), and plasma electrolytes. The
      Hamilton depression rating scale with 21 items was primarily used to determine
      depression severity. In the overall sample, STI increased and SP decreased
      significantly with treatment without a clear relationship with treatment outcome.
      No other significant changes were observed. Reductions in cortisol and
      aldosterone after 2 weeks of treatment were significantly related to improvement
      after 6 weeks (P<0.05). SWS increase after 2 and 6 weeks was by trend (P<0.08)
      correlated to clinical improvement after 6 weeks. Systolic blood pressure
      differentiated responders and nonresponders at baseline (P<0.05), but did not
      change significantly during treatment. We earlier identified a relationship
      between clinical outcome and baseline values of STI, SP, and RSA only in male
      patients; therefore, changes in this subgroup were analyzed separately: in male
      treatment responders, a trend toward an increase in SWS occurred after 2 (P<0.07)
      and 6 (P<0.07) weeks. Further, a trend toward RSA reduction (P<0.07) was
      observed. Changes in STI and SP were similar to the total group, but did not
      reach levels of significance. Early changes in central MR-related biomarkers
      appear to influence the outcome of standard antidepressant treatment: reduced
      salivary cortisol, increased SWS, and reduced RSA are linked to a better
      treatment outcome. These features point to a mechanism involving increased
      central MR activation in responders to standard antidepressants, but not in
      nonresponders.

PMID- 30300166
TI  - Anaesthesia care team improves outcomes in surgical patients compared with solo
      anaesthesiologist: An observational study.
AB  - BACKGROUND: In anaesthesiology, little attention has been drawn to the role of
      anaesthesia nurses as support personnel on quality of care. OBJECTIVES: To
      compare an anaesthesiologist alone (solo anaesthesiologist) with an anaesthesia
      care team (anaesthesiologist and anaesthesia nurse). DESIGN: An observational
      study. SETTING: A single centre study. PARTICIPANTS: Anaesthesiologists and
      anaesthesia nurses. INTERVENTION: Anaesthesia performed by solo
      anaesthesiologists compared with anaesthesia care teams. MAIN OUTCOME MEASURES:
      30-day postoperative mortality and hospital length of stay. Propensity score
      matching was performed by logistic regression to adjust for baseline differences
      between the two groups and pairs of perfectly matched patients were formed.
      RESULTS: Anaesthesia was performed by solo anaesthesiologists in 2832 patients
      and by an anaesthesia care team in 2842 patients. Matching with 2095 pairs of
      perfectly matched patients was formed. The two groups were comparable in respect
      of sex and duration of anaesthesia but differed notably for age, American Society
      of Anesthesiologists' physical status score and type of surgery. Logistic
      regression showed a significantly lower 30-day mortality rate for the anaesthesia
      care teams compared with solo anaesthesiologists (0.76 vs. 1.56%, P = 0.0014).
      Length of hospital stay was also significantly reduced when an anaesthesia nurse
      was present (4.9 +/- 10.1 vs. 5.6 +/- 11.5 days, P = 0.0011). CONCLUSION:
      Anaesthesia given by teams of anaesthesiologists and anaesthesia nurses is
      associated with decreased 30-day postoperative mortality and shorter length of
      stay when compared with solo anaesthesiologists. Even without any demonstration
      of causality, this emphasises the benefits of the anaesthesia care team model.
      TRIAL REGISTRATION: CCB 325201730849.

PMID- 30300167
TI  - Phonemic fluency improved after inhibitory transcranial magnetic stimulation in a
      case of chronic aphasia.
AB  - Twenty-six months after a left hemispheric ischemic stroke an aphasic patient
      showed a significant improvement in verbal fluency following ten daily sessions
      of inhibitory 1 Hz repetitive transcranial magnetic stimulation over the right
      cortex homologous to the Broca's area.No improvement was observed for other
      linguistic functions or for executive ones. Results confirm the segregation of
      neural circuitries subtending phonemic and semantic fluency and suggest a
      selective usefulness of the repetitive transcranial magnetic stimulation
      treatment.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- 30300168
TI  - Factors Affecting Racial Disparities in End-of-Life Care Costs Among Lung Cancer
      Patients: A SEER-Medicare-based Study.
AB  - OBJECTIVES: Racial disparities exist in end-of-life lung cancer care, which could
      potentially lead to considerable racial differences in end-of-life care costs.
      This study for the first time estimates the racial differences in end-of-life
      care costs among lung cancer patients, and identifies and quantifies factors that
      contribute the most to these differences using a statistical decomposition
      method. METHODS: This is a retrospective analysis of patients 66 years and older,
      diagnosed with stage I-IV lung cancer, who died on or before December 31, 2013,
      using the Surveillance Epidemiology and End Result-Medicare data from 1991 to
      2013. Ordinary least square regression of logarithmically transformed cost was
      used to estimate racial differences in end-of-life care costs among lung cancer
      patients. Blinder-Oaxaca decomposition was used to identify and quantify factors
      that contributed the most to these differences. RESULTS: Non-Hispanic blacks had
      10% to 13% higher end-of-life care costs as compared with non-Hispanic whites.
      Geographic variations, baseline comorbidity indices and stage at diagnosis
      contributed the most to explaining the racial differences in costs, with
      geographic variation explaining most of the differences. However, the observed
      factors could only explain 25% to 32% of the racial differences in end-of-life
      care costs. CONCLUSIONS: Geographic differences in access to timely and
      appropriate care, and provider practice patterns, should be examined to
      understand the reasons behind geographic variations in racial disparity. Provider
      level educational interventions to reduce small area practice variations and
      differential management of patients by race, as well as racially sensitive
      patient-level educational and navigational interventions might be critical in
      improving quality of care and reducing costs during end-of-life.

PMID- 30300169
TI  - How to Optimize Cancer Treatment in Older Patients: An Overview of Available
      Geriatric Tools.
AB  - Cancer is a disease of older people, but this age group has often been excluded
      from clinical trials of cancer, which leads to poor transportability of
      standardized treatments in older cancer patients. One of the main reasons for the
      exclusion is the heterogeneity of older people in several domains: social
      environment, comorbidities, dependency, functional status, nutritional status,
      cognition status, and mood status. Comprehensive geriatric assessment aims to
      assess this heterogeneity and has identified frequent health problems often
      unknown before therapeutic decisions, which allows for targeted geriatric
      interventions with or without follow-up and appropriate cancer treatment
      selection. Several tools and scores have been developed for a complementary
      approach. These tools have the following characteristics: they screen for
      vulnerability to select patients who may benefit from a comprehensive geriatric
      assessment; are predictive tools for survival, postoperative complications, or
      chemotherapy-related toxicity; are decisional algorithms for cancer treatment; or
      define a core set of geriatric data to be collected in clinical cancer trials.
      Here, we present an overview of the geriatric tools that were published in PubMed
      from 2000 to 2017, that could help in the therapeutic decision-making for older
      cancer patients.

PMID- 30300170
TI  - Factors Associated With Head and Neck Cancer Hospitalization Cost and Length of
      Stay-A National Study.
AB  - OBJECTIVES: The aim of the study was to estimate hospitalization cost, and
      factors associated with hospitalization costs and length of stay (LOS) of
      patients treated for head and neck cancer in the United States. METHODS: Data on
      71,440 weighted hospital admissions from the 2014 National Inpatient Sample with
      a diagnosis of head and neck cancer were examined. Multivariable linear
      regression models estimated factors associated with hospitalization costs, and
      negative binomial regression models were used to identify factors associated with
      hospital LOS. Factor variables included characteristics of the patient, clinical,
      and hospital characteristics. RESULTS: The average hospitalization cost was US
      $18,371 and the average LOS was 6.6 days. LOS was significantly associated with
      admissions involving bacterial infection, major operating procedures, chemo
      procedure, and radiation procedure as well as admissions at medium or small bed
      size hospitals, and rural hospitals. Admissions among black patients, elective
      admissions, admissions involving bacterial infection, major operating procedures,
      chemo procedure, radiation procedure, and advance comorbidities were associated
      with increased hospitalization costs. In contrast, admissions at urban
      nonteaching or rural had increased hospitalization costs. CONCLUSIONS: Admissions
      that involve higher number of comorbidities, metastasis, bacterial infection,
      radiation, and chemo procedures had longer hospital stay and higher cost whereas
      admissions are rural hospitals had shorter hospital stay and lower cost.
      Understanding these factors associated with increased LOS and hospitalization
      cost will help efforts to decrease health care cost and improve quality of care.

PMID- 30300171
TI  - Effect of Apneic Oxygenation on Tracheal Oxygen Levels, Tracheal Pressure, and
      Carbon Dioxide Accumulation: A Randomized, Controlled Trial of Buccal Oxygen
      Administration.
AB  - BACKGROUND: Apneic oxygenation via the oral route using a buccal device extends
      the safe apnea time in most but not all obese patients. Apneic oxygenation
      techniques are most effective when tracheal oxygen concentrations are maintained
      >90%. It remains unclear whether buccal oxygen administration consistently
      achieves this goal and whether significant risks of hypercarbia or barotrauma
      exist. METHODS: We conducted a randomized trial of buccal or sham oxygenation in
      healthy, nonobese patients (n = 20), using prolonged laryngoscopy to maintain
      apnea with a patent airway until arterial oxygen saturation (SpO2) dropped <95%
      or 750 seconds elapsed. Tracheal oxygen concentration, tracheal pressure, and
      transcutaneous carbon dioxide (CO2) were measured throughout. The primary outcome
      was maintenance of a tracheal oxygen concentration >90% during apnea. RESULTS:
      Buccal patients were more likely to achieve the primary outcome (P < .0001), had
      higher tracheal oxygen concentrations throughout apnea (mean difference, 65.9%;
      95% confidence interval [CI], 62.6%-69.3%; P < .0001), and had a prolonged median
      (interquartile range) apnea time with SpO2 >94%; 750 seconds (750-750 seconds) vs
      447 seconds (405-525 seconds); P < .001. One patient desaturated to SpO2 <95%
      despite 100% tracheal oxygen. Mean tracheal pressures were low in the buccal
      (0.21 cm.H2O; SD = 0.39) and sham (0.56 cm.H2O; SD = 1.25) arms; mean difference,
      -0.35 cm.H2O; 95% CI, 1.22-0.53; P = .41. CO2 accumulation during early apnea
      before any study end points were reached was linear and marginally faster in the
      buccal arm (3.16 vs 2.82 mm Hg/min; mean difference, 0.34; 95% CI, 0.30-0.38; P <
      .001). Prolonged apnea in the buccal arm revealed nonlinear CO2 accumulation that
      declined over time and averaged 2.22 mm Hg/min (95% CI, 2.21-2.23). CONCLUSIONS:
      Buccal oxygen administration reliably maintains high tracheal oxygen
      concentrations, but early arterial desaturation can still occur through
      mechanisms other than device failure. Whereas the risk of hypercarbia is similar
      to that observed with other approaches, the risk of barotrauma is negligible.
      Continuous measurement of advanced physiological parameters is feasible in an
      apneic oxygenation trial and can assist with device evaluation.

PMID- 30300172
TI  - Contemporary Academic Contributions From Anesthesiologists in Adult Critical Care
      Medicine.
AB  - BACKGROUND: Anesthesiology has a long relationship with critical care medicine
      (CCM). However, US anesthesiologists are less likely to practice CCM than non-US
      anesthesiologists. To date, no studies have compared academic contributions in
      CCM between US anesthesiologists and non-US anesthesiologists. The objective of
      our study was to use recent trends in critical care publications as a surrogate
      for academic contribution among US and non-US anesthesiologists. METHODS:
      Research articles published between 2010 and 2015 in 3 anesthesiology journals
      (Anesthesiology, Anesthesia & Analgesia, and British Journal of Anaesthesia) and
      3 multidisciplinary CCM journals (Critical Care Medicine, Intensive Care
      Medicine, and Journal of Critical Care) were reviewed. Author information,
      including the primary department appointment and geographic location for the
      first and senior author(s), and article details, including topic and publication
      type, were collected. Odds ratios for having a first or senior author from the
      United States were calculated. Anesthesiologists' contributions in individual
      journals were summarized, as were trends in anesthesiology CCM publications
      during the 6-year study period. RESULTS: A total of 3831 articles were reviewed,
      with 1050 (27.4%) having US authors. Eighty-two and one-half percent of CCM
      articles in anesthesiology journals had a US anesthesiologist as first author,
      and 81% had a US anesthesiologist as senior author, while fewer CCM articles in
      multidisciplinary journals had a US anesthesiologist as first (12.1%) or senior
      (12.3%) author. When considering all publications, 16.3% and 16.4% of articles
      had a US anesthesiologist as the first or senior author compared with articles
      for which non-US anesthesiologists were first (23.8%) or senior (20.9%) authors.
      The odds of having a US anesthesiologist as first or senior author compared to a
      non-US anesthesiologist for all publications were 0.6 (0.5-0.7) and 0.7 (0.6
      0.9). The number of publications trended downward for both US anesthesiologists
      and non-US anesthesiologists during the study period. CONCLUSIONS: When compared
      to non-US anesthesiologists, US anesthesiologists had more CCM publications in
      anesthesiology journals and fewer publications in multidisciplinary CCM journals.
      The number of anesthesiology CCM publications decreased for both US and non-US
      anesthesiologists throughout the study period.

PMID- 30300173
TI  - Mild Perioperative Hypothermia and Myocardial Injury: A Retrospective Cohort
      Analysis.
AB  - BACKGROUND: We tested the primary hypothesis that final intraoperative esophageal
      temperature is associated with increased odds of a composite of in-hospital all
      cause mortality and myocardial injury within 7 days after noncardiac surgery.
      Secondary exposures were time-weighted average intraoperative temperature and
      area <37 degrees C threshold. METHODS: Myocardial injury was defined by
      postoperative fourth-generation troponin T >=0.03 ng/mL apparently due to cardiac
      ischemia. Data were extracted for inpatients who had noncardiac surgery with
      general anesthesia at the Cleveland Clinic between 2012 and 2015. All had
      esophageal temperature monitoring and routine postoperative troponin monitoring.
      We estimated the confounder-adjusted association between final intraoperative
      esophageal temperature and the collapsed composite with multivariable logistic
      regression. We similarly estimated associations with time-weighted average
      intraoperative temperature and area <37 degrees C. RESULTS: Two thousand two
      hundred ten patients were included. Nearly all final esophageal temperatures were
      36 degrees C-37 degrees C. Ninety-seven patients (4.4%) had myocardial injury,
      and 7 (0.3%) died before discharge. Final intraoperative core temperature was not
      associated with the collapsed composite: odds ratio, 0.91 (95% confidence
      interval, 0.68-1.24) per 1 degrees C decrease. Similarly, neither of the
      secondary exposures was associated with the composite outcome. CONCLUSIONS: We
      did not observe an association between mild perioperative hypothermia and
      mortality or myocardial injury in adults having noncardiac surgery. However, the
      range of final intraoperative temperatures was small and largely restricted to
      the normothermic range (36 degrees C-37 degrees C). Trials are needed to further
      assess the effect of temperature on myocardial injury.

PMID- 30300174
TI  - Intensive Care Unit Readmission After Left Ventricular Assist Device
      Implantation: Causes, Associated Factors, and Association With Patient Mortality.
AB  - BACKGROUND: Previous studies on readmissions after left ventricular assist device
      (LVAD) implantation have focused on hospital readmissions after dismissal from
      the index hospitalization. Because few data exist, the purpose of this study was
      to examine intensive care unit (ICU) readmissions in patients during their
      initial hospitalization for LVAD implantation to determine reasons for, factors
      associated with, and incidence of mortality after ICU readmission. METHODS: A
      retrospective analysis was performed from February 2007 to March 2015 of patients
      at our institution receiving first-time LVAD implantation. After LVAD
      implantation, patients dismissed from the ICU who then required ICU readmission
      before hospital dismissal were compared to those not requiring ICU readmission
      before hospital dismissal with respect to preoperative, intraoperative, and
      postoperative factors. RESULTS: Among 287 LVAD patients, 266 survived their
      initial ICU admission, of which 49 (18.4%) required ICU readmission. The most
      common reasons for readmission were bleeding and respiratory failure. Factors
      found to be univariably associated with ICU readmission were preoperative
      hemoglobin, preoperative aspartate aminotransferase, preoperative atrial
      fibrillation, preoperative dialysis, longer cardiopulmonary bypass times, and
      higher intraoperative allogeneic blood transfusion requirements. Multivariable
      analysis revealed ICU readmission to be independently associated with
      preoperative dialysis (odds ratio, 12.86; 95% confidence interval, 3.16-52.28; P
      < .001). Overall mortality at 1 year was 22.6%. Survival after hospital dismissal
      was worse for patients who required ICU readmission during the index
      hospitalization (adjusted hazard ratio, 2.35; 95% confidence interval, 1.15-4.81;
      P = .019). CONCLUSIONS: ICU readmission after LVAD implantation occurred
      relatively frequently and was significantly associated with 1-year mortality
      after hospital dismissal. These data can perhaps be used to identify subsets of
      LVAD patients at risk for ICU readmission and may lead to implementation of
      practice changes to mitigate ICU readmissions. Future larger and prospective
      studies are warranted.

PMID- 30300175
TI  - Recognizing the Chinese Pioneer of Neuraxial Labor Analgesia: Dr Guang-Bo Zhang
      and Her Unpublished Manuscript From More Than a Half-Century Ago.
AB  - Dr Guang-Bo Zhang was the first anesthesiologist to administer and study the
      effects of labor epidural analgesia in China. Between September 1963 and March
      1964, she conducted an observational study evaluating the effects of neuraxial
      analgesia for laboring women. She presented her research and prepared an article;
      however, due to the Great Proletarian Cultural Revolution (Cultural Revolution),
      which began in 1966, her work went unpublished. She successfully preserved her
      unpublished article, notes, and slides throughout the Cultural Revolution by
      hiding them in a countryside location near Beijing. These 54-year-old, previously
      unpublished documents represent the first known clinical trial of neuraxial labor
      analgesia conducted in China.

PMID- 30300176
TI  - Emergency Department Airway Management Responsibilities in the United States.
AB  - BACKGROUND: In the 1990s, emergency medicine (EM) physicians were responsible for
      intubating about half of the patients requiring airway management in emergency
      rooms. Since then, no studies have characterized the airway management
      responsibilities in the emergency room. METHODS: A survey was sent via the
      Eastern Association for Surgery and Trauma and the Trauma Anesthesiology Society
      listservs, as well as by direct solicitation. Information was collected on trauma
      center level, geographical location, department responsible for intubation in the
      emergency room, department responsible for intubation in the trauma bay, whether
      these roles differed for pediatrics, whether an anesthesiologist was available
      "in-house" 24 hours a day, and whether there was a protocol for anesthesiologists
      to assist as backup during intubations. Responses were collected, reviewed,
      linked by city, and mapped using Python. RESULTS: The majority of the responses
      came from the Eastern Association for Surgery of Trauma (84.6%). Of the
      respondents, 72.6% were from level-1 trauma centers, and most were located in the
      eastern half of the United States. In the emergency room, EM physicians were
      primarily responsible for intubations at 81% of the surveyed institutions. In
      trauma bays, EM physicians were primarily responsible for 61.4% of intubations.
      There did not appear to be a geographical pattern for personnel responsible for
      managing the airway at the institutions surveyed. CONCLUSIONS: The majority of
      institutions have EM physicians managing their airways in both emergency rooms
      and trauma bays. This may support the observations of an increased percentage of
      airway management in the emergency room and trauma bay setting by EM physicians
      compared to 20 years ago.

PMID- 30300177
TI  - Fluid Challenge During Anesthesia: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Assessing the volemic status of patients undergoing surgery is part
      of the routine management for the anesthesiologist. This assessment is commonly
      performed by means of dynamic indexes based on the cardiopulmonary interaction
      during mechanical ventilation (if available) or by administering a fluid
      challenge (FC). The FC is used during surgery to optimize predefined hemodynamic
      targets, the so-called Goal-Directed Therapy (GDT), or to correct hemodynamic
      instability (non-GDT). METHODS: In this systematic review, we considered the FC
      components in studies adopting either GDT or non-GDT, to assess whether
      differences exist between the 2 approaches. In addition, we performed a meta
      analysis to ascertain the effectiveness of dynamic indexes pulse pressure
      variation (PPV) and stroke volume (SV) variation (SVV), in predicting fluid
      responsiveness. RESULTS: Thirty-five non-GDT and 33 GDT studies met inclusion
      criteria, including 5017 patients. In the vast majority of non-GDT and GDT
      studies, the FC consisted in the administration of colloids (85.7% and 90.9%,
      respectively). In 29 non-GDT studies, the colloid infused was the 6% hydroxyethyl
      starch (6% HES; 96.6% of this subgroup). In 20 GDT studies, the colloid infused
      was the 6% HES (66.7% of this subgroup), while in 5 studies was a gelatin (16.7%
      of this subgroup), in 3 studies an unspecified colloid (10.0% of this subgroup),
      and in 1 study albumin (3.3%) or, in another study, both HES 6% and gelatin
      (3.3%). In non-GDT studies, the median volume infused was 500 mL; the time of
      infusion and hemodynamic target to assess fluid responsiveness lacked
      standardization. In GDT studies, FC usually consisted in the administration of
      250 mL of colloids (48.8%) in 10 minutes (45.4%) targeting an SV increase >10%
      (57.5%). Only in 60.6% of GDT studies, a safety limit was adopted. PPV pooled
      area under the curve (95% confidence interval [CI]) was 0.86 (0.80-0.92). The
      mean (standard deviation) PPV threshold predicting fluid responsiveness was 10.5%
      (3.2) (range, 8%-15%), while the pooled (95% CI) sensitivity and specificity were
      0.80 (0.74-0.85) and 0.83 (0.73-0.91), respectively. SVV pooled area under the
      curve (95% CI) was 0.87 (0.81-0.93). The mean (standard deviation) SVV threshold
      predicting fluid responsiveness was 11.3% (3.1) (range, 7.5%-15.5%), while the
      pooled (95% CI) sensitivity and specificity were 0.82 (0.75-0.89) and 0.77 (0.71
      0.82), respectively. CONCLUSIONS: The key components of FC including type of
      fluid (colloids, often 6% HES), volume (500 and 250 mL in non-GDT studies and GDT
      studies, respectively), and time of infusion (10 minutes) are quite standardized
      in operating room. However, pooled sensitivity and specificity of both PPV and
      SVV are limited.

PMID- 30300179
TI  - The Importance of Differentiating Charges and Cost.

PMID- 30300178
TI  - Regional Analgesia Added to General Anesthesia Compared With General Anesthesia
      Plus Systemic Analgesia for Cardiac Surgery in Children: A Systematic Review and
      Meta-analysis of Randomized Clinical Trials.
AB  - BACKGROUND: The aim of this systematic review was to compare the effects of
      regional analgesic (RA) techniques with systemic analgesia on postoperative pain,
      nausea and vomiting, resources utilization, reoperation, death, and complications
      of the analgesic techniques in children undergoing cardiac surgery. METHODS: A
      search was done in May 2018 in PubMed, Embase, and the Cochrane Central Register
      of Controlled Trials for randomized controlled trials comparing RA techniques
      with systemic analgesia. Risks of bias of included trials were judged with the
      Cochrane tool. Data were analyzed with fixed- (I < 25%) or random-effects models
      (I >= 25%). The quality of evidence was graded according to the Grading of
      Recommendations Assessment, Development, and Evaluation working group scale.
      RESULTS: We included 14 randomized controlled trials with 605 participants (312
      to RA and 293 to the comparator). RA reduces pain up to 24 hours after surgery.
      At 6-8 hours after surgery, the standardized mean difference was -0.81 (95%
      confidence interval [CI], -1.22 to -0.40; low-quality evidence). We did not find
      a difference for nausea and vomiting (risk ratio [RR], 0.89; 95% CI, 0.61-1.31;
      very low-quality evidence), duration of tracheal intubation (standardized mean
      difference, -0.18; 95% CI, -0.40 to 0.05; low-quality evidence), intensive care
      unit length of stay (mean difference, -0.10 hours; 95% CI, -1.31 to 1.12 hours;
      low-quality evidence), hospital length of stay (mean difference, -0.02 days; 95%
      CI, -1.16 to 1.12 days; low-quality evidence), reoperation (RR, 0.76; 95% CI,
      0.17-3.28; low-quality evidence), death (RR, 0.50; 95% CI, 0.05-4.94; low-quality
      evidence), and respiratory depression (RR, 2.06; 95% CI, 0.20-21.68; very low
      quality evidence). No trial reported signs of local anesthetic toxicity or
      lasting neurological or infectious complications related to the RA techniques.
      One trial reported 1 transient ipsilateral episode of diaphragmatic paralysis
      with intrapleural analgesia that resolved with cessation of local anesthetic
      administration. CONCLUSIONS: Compared to systemic analgesia, RA techniques reduce
      postoperative pain up to 24 hours in children undergoing cardiac surgery.
      Currently, there is no evidence that RA for pediatric cardiac surgery has any
      impact on major morbidity and mortality. These results should be interpreted
      cautiously because they represent a meta-analysis of small and heterogeneous
      studies. Further studies are needed.

PMID- 30300180
TI  - Use of the Bougie Endotracheal Tube Introducer in Unstable Cervical Spine Airway
      Management?

PMID- 30300181
TI  - Resting Hemodynamics and Response to Exercise Using the 6-Minute Walk Test in
      Late Pregnancy: An International Prospective Multicentre Study.
AB  - BACKGROUND: Cardiac disease is the leading cause of maternal death. Assessment of
      cardiovascular fitness is important in pregnant women because it is linked to
      increased risk of cardiac disease but is rarely undertaken or studied. The 6
      Minute Walk Test (6MWT) is a safe exercise test but is not used in pregnancy. We
      determined the 95% reference interval for resting heart rate (HR) and distance
      walked for the 6MWT, as well as hemodynamic recovery variables, and quantified
      expectations and actual experiences of exertion and breathlessness with exercise
      in late pregnancy. METHODS: After institutional research board approval
      (Australian and New Zealand Clinical Trials Registry Number: 12615000964516), 300
      healthy term nulliparous pregnant women performed the 6MWT at 3 tertiary referral
      obstetric hospitals using a standardized protocol. Each woman underwent two 6MWT
      with maximum 15-minute recovery period after each test. Hemodynamic variables
      were measured at rest and after exercise. Participants were asked 4 questions, 2
      regarding expectation and 2 regarding actual experience, using the Rating of
      Perceived Exertion scale and Modified Borg Dyspnea scale. RESULTS: Participant
      characteristics and resting variables were mean (standard deviation [SD]); age,
      31 years (4.2 years); body mass index, 27 kg/m (2.9 kg/m); gestational age, 37
      weeks (1.3 weeks); HR, 85 bpm (10.8 bpm) with 95% reference interval 64-106 bpm;
      systolic blood pressure, 112 mm Hg (10.2 mm Hg); diastolic blood pressure, 72 mm
      Hg (8.6 mm Hg); oxygen saturation, 98% (0.9%); and respiratory rate, 18
      breaths/min (5.7 breaths/min). The mean (SD) average distance walked was 488 m
      (94.9 m) with a speed of 3.0 mph (0.64 mph) with a 95% reference interval of 302
      674 m. The mean (SD) HR increase with exercise was 12 bpm (11.0 bpm) with a
      median [quartile] recovery time of 5.0 minutes [1-8 minutes]. A lower resting HR
      was associated with increased distance walked (r = -0.207; 95% confidence
      interval, -0.313 to -0.096; P < .001). A greater HR change with exercise was
      associated with increased recovery time from exercise (r = 0.736; 95% confidence
      interval, 0.697-0.784; P < .001). Sixty-three percent and 83% of participants,
      respectively, expected to be more exerted and breathless than they actually were
      with exercise. CONCLUSIONS: The 6MWT is feasible and applicable in term pregnant
      women. The reference intervals for resting HR and distance walked in the 6MWT
      have been generated. HR increases by approximately 12 bpm with submaximal
      exercise, and half of the women recovered within 5 minutes of submaximal
      exercise. Women expected to be more exerted and breathless than they actually
      were with exercise.

PMID- 30300182
TI  - Implementing a Pediatric Perioperative Surgical Home Integrated Care Coordination
      Pathway for Laryngeal Cleft Repair.
AB  - BACKGROUND: The Pediatric Perioperative Surgical Home (PPSH) model is an
      integrative care model designed to provide better patient care and value by
      shifting focus from the patient encounter level to the overarching surgical
      episode of care. So far, no PPSH model has targeted a complex airway disorder. It
      was hypothesized that the development of a PPSH for laryngeal cleft repair would
      reduce the high rates of postoperative resource utilization observed in this
      population. METHODS: Institutional review board approval was obtained for the
      purpose of data collection and analysis. A multidisciplinary team of
      anesthesiologists, surgeons, nursing staff, information technology specialists,
      and finance administrators was gathered during the PPSH development phase.
      Standardized perioperative (preoperative, intraoperative, and postoperative)
      protocols were developed, with a focus on preoperative risk stratification.
      Patients presenting before surgery with >=1 predefined medical comorbidity were
      triaged to the intensive care unit (ICU) postoperatively, while patients without
      severe systemic disease were triaged to a lower-acuity floor for overnight
      observation. The success of the PPSH protocol was defined by quality outcome and
      value measurements. RESULTS: The PPSH initiative included 120 patients, and the
      pre-PPSH period included 115 patients who underwent laryngeal cleft repair before
      implementation of the new process. Patients in the pre-PPSH period were reviewed
      and classified as ICU candidates or lower acuity floor candidates had they
      presented in the post-PPSH period. Among the 79 patients in the pre-PPSH period
      who were identified as candidates for the lower-acuity floor transfer, 70
      patients (89%) were transferred to the ICU (P < .001). Retrospective analysis
      concluded that 143 ICU bedded days could have been avoided in the pre-PPSH group
      by using PPSH risk stratification. Surgery duration (P = .034) and hospital
      length of stay (P = .015) were found to be slightly longer in the group of pre
      PPSH observation unit candidates. Rates of 30-day unplanned readmissions to the
      hospital were not associated with the new PPSH initiative (P = .093). No patients
      in either group experienced emergent postoperative intubation or other expected
      complications. Total hospital costs were not lower for PPSH observation unit
      patients as compared to pre-PPSH observation unit candidates (difference = 8%;
      95% confidence interval, -7% to 23%). CONCLUSIONS: A well-defined preoperative
      screening protocol for patients undergoing laryngeal cleft repair can reduce
      postoperative ICU utilization without affecting patient safety. Further research
      is needed to see if these findings are applicable to other complex airway
      surgeries.

PMID- 30300183
TI  - In Response.

PMID- 30300184
TI  - ACCEPTANCE SPEECH GIVEN BY SHAHEEN A. DEWJI, RECIPIENT OF THE 2018 ELDA E.
      ANDERSON AWARD: at the 63rd Annual Meeting of the Health Physics Society
      Cleveland, Ohio 15-19 July 2018.

PMID- 30300185
TI  - 2018 HONOR ROLL AWARD: Presented to FRANCIS M. COSTELLO at the 63rd Annual
      Meeting of the Health Physics Society Cleveland, Ohio 15-19 July 2018.

PMID- 30300186
TI  - Designing and Developing a Mobile App for Clinical Decision Support: An
      Interprofessional Collaboration.

PMID- 30300187
TI  - 2018 Nursing Knowledge Big Data Science Initiative.

PMID- 30300188
TI  - Exploring the State of the Science of the Nursing Hand-off Communication.

PMID- 30300190
TI  - Blunt Abdominal Trauma in Sports.

PMID- 30300191
TI  - Use of Foot Doming for Increasing Dynamic Stability and Injury Prevention in
      Runners and Athletes.

PMID- 30300192
TI  - Billing and Coding in Sports Medicine.

PMID- 30300193
TI  - Antidoping Science: Important Lessons From the Medical Sciences.
AB  - The ineffectiveness of antidoping programs in elite sport, largely due to human
      and political factors, is leading to a new resolve and greater transparency of
      antidoping authorities and those stakeholders interested in drug-free sport. The
      perception by the public, athletes, and the World Anti-Doping Agency (WADA) of
      antidoping science and current drug testing programs in elite sport varies widely
      from "ineffective" to "robust and reliable." Here, we discuss why a careful and
      considered reevaluation of the underlying premise of antidoping science is needed
      to bring this unique application of predictive/diagnostic science more in line
      with other areas of medicine. We show how the validity of doping tests are
      neither "stand-alone figures" generated under ideal laboratory conditions, nor
      figures that can be used in isolation to support the efficacy of the current drug
      testing program. Given the consequences of a failed doping test for the athlete,
      the sport, and multiple stakeholders (e.g., the sponsors), there is a need for
      transparent decision making to ensure those affected are well informed. We
      identify in this perspective the minimal essential data on drug testing that
      should be reported by antidoping laboratories to draw meaningful conclusions
      about the effectiveness of specific drug testing methods to support antidoping.
      In the absence of information on the validity of a doping test, it is not
      possible to plan or conduct "intelligent testing." It is imperative that the
      prevalence of doping and the likelihood of false-positive doping tests be
      regularly updated and made available for the wider antidoping research community
      to explore new approaches that could improve the validity of antidoping tests.
      True confirmatory testing which requires the use of different analytical
      technology and ideally an independent sample taken from an athlete with a
      positive test to transcend the present-day analysis of the B-sample. Indirect
      biomarkers of doping derived from new "omics"-based approaches may significantly
      improve the testing strategy. Biomarker molecular signatures are flexible enough
      to develop "normal ranges" optimized for either test sensitivity or specificity
      to detect a plethora of doping substances and methods.

PMID- 30300194
TI  - GPS Tracker-Enabled Rescue of a Lost Runner During a Wilderness Ultramarathon: A
      Case Report.

PMID- 30300195
TI  - Olecranon Fracture from Direct Trauma to Elbow during a Baseball Game: A Case
      Report.

PMID- 30300196
TI  - Scapula Dyskinesis: A Review of Current Concepts and Evaluation of Assessment
      Tools.
AB  - Scapula dyskinesis is prevalent in athletes conducting forceful overhead
      movements. This review summarizes our current understanding of the condition and
      evaluates the different options for assessing dyskinesis. Current methods for
      assessing scapula dyskinesis involve clinical observations, three-dimensional
      kinematics and three-dimensional wing computer tomography. Clinical observation
      is the most pragmatic method for assessing dyskinesis yielding inter-rater
      agreement of 79% and sensitivity of 76%. Similar sensitivities have been recorded
      using three-dimensional kinematics. Three-dimensional wing computer tomography
      has yielded a near-perfect interclass correlation coefficient of 0.972 when used
      to assess dyskinesis. Three-dimensional wing computer tomography, given its
      expense, low availability, and levels of irradiation, should be reserved for high
      performance athletes where detailed assessments need to be made to aid
      rehabilitation. Observational assessments should remain the main modality used
      for general assessment.

PMID- 30300197
TI  - Don't Just Blame it on the Veins: An Update on Vascular Exertional Limb Pain.
AB  - Exertional limb pain is a common problem encountered in recreational and
      competitive athletes. Affecting both the upper and lower extremities, this broad
      entity can be musculoskeletal, vascular, neurologic, oncologic, or infectious in
      origin. This article focuses on the vascular causes of exercise-related extremity
      pain, which encompass a cadre of elusive diagnoses. Specifically, we examine
      arterial endofibrosis, popliteal artery entrapment syndrome, and chronic
      exertional compartment syndrome of both the upper and lower extremities. For each
      of these conditions, we offer updates regarding the respective epidemiology,
      common signs and symptoms, worthwhile diagnostic modalities, and pertinent
      treatment options, all based on evidence and reports published over the past
      year.

PMID- 30300198
TI  - Occult Giant Cell Arteritis Concurrent With Pancreatic Carcinoma Revealed by 18F
      FDG PET/CT.
AB  - An F-FDG PET/CT was performed on a 74-year-old woman with pancreatic carcinoma
      and liver metastases. Occult giant cell arteritis, involving the aorta, truncus
      brachiocephalicus, subclavian arteries, axillaries, external carotid arteries,
      vertebral arteries, and superficial temporal arteries, was accidentally revealed.

PMID- 30300199
TI  - Splenosis of the Liver Capsule.
AB  - Splenosis, a form of ectopic splenic tissue, is generally caused by heterotopic
      autotransplantation of splenic tissues after traumatic splenic rupture or
      splenectomy. The implants are often localized intraperitoneally, mostly in the
      left upper quadrant and splenic region. Hepatic foci are seen only on rare
      occasions. The differential diagnosis of splenosis foci from malignant masses can
      be challenging by conventional imaging and lead to unnecessary invasive
      procedures. This manuscript presents radiological and scintigraphic images of
      splenosis foci located in the peritoneal cavity and liver capsule of a 46-year
      old man who underwent splenectomy due to traumatic splenic rupture 30 years ago.

PMID- 30300200
TI  - Prognostic Value of Volumetric Parameters of Pretreatment 18F-FDG PET/CT in
      Esophageal Cancer: A Systematic Review and Meta-analysis.
AB  - PURPOSE: We performed a systematic review and meta-analysis on the prognostic
      value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived
      from pretreatment F-FDG PET/CT in patients with esophageal cancer. METHODS:
      PubMed and EMBASE databases were searched until April 12, 2018, for studies that
      evaluated MTV or TLG as prognostic factors in esophageal cancer, with overall
      survival (OS) and event-free survival serving as the end points. Hazard ratios
      (HRs) were meta-analytically pooled using a random-effects model. Subgroup
      analyses based on the clinicopathological and PET variables were performed.
      RESULTS: In total, 16 studies with 1294 patients were included. The pooled HRs of
      MTV and TLG for OS were 2.26 (95% confidence interval [CI], 1.73-2.96) and 2.23
      (95% CI, 1.73-2.87), respectively. Regarding event-free survival, the pooled HRs
      of MTV and TLG were 2.03 (95% CI, 1.66-2.49) and 2.57 (95% CI, 1.82-3.62),
      respectively. Metabolic tumor volume was found to be a significant prognostic
      factor for OS consistently across multiple subgroups classified based on stage,
      histological subtype, treatment, delineation of volume of interest, and the
      determination method of cutoff value, with pooled HRs ranging from 1.96 to 2.54.
      CONCLUSIONS: In patients with esophageal cancer, MTV and TLG derived from
      pretreatment F-FDG PET are significant prognostic factors. As prognostic
      biomarkers, volumetric metabolic parameters may bolster the role of F-FDG PET in
      the management of esophageal cancer.

PMID- 30300201
TI  - Endometrioid Intraepithelial Neoplasia: An Endometrial Precancer Detected by 18F
      FDG PET/CT.
AB  - The report describes a 55-year-old woman with postmenopausal abnormal vaginal
      spotting. PET/CT revealed focal hot F-FDG uptake in the fundus portion of the
      uterine cavity, and pathology of hysteroscopic dilation and curettage showed
      endometrioid intraepithelial neoplasia of uterine endometrium, an endometrial
      precancer. This case points to the significance of F-FDG PET/CT in determining
      the dilation and curettage site for the postmenopausal women with abnormal
      vaginal spotting. Increased F-FDG activity in the region of the uterus must be
      investigated to determine the possibilities of primary malignancies, metastases,
      and benign diseases.

PMID- 30300202
TI  - 18F-Choline and 18F-FDG PET/CT in a Patient With Diffuse Large B-Cell Lymphoma
      and Recurrent Prostate Cancer.
AB  - We report herein the case of an 80-year-old man who was referred for a
      biochemical recurrence of a high-risk prostate cancer. In addition to prostate
      cancer recurrence, F-choline allowed partial initial staging of an incidental
      diffuse large B-cell lymphoma which was further confirmed and staged using F-FDG
      and a biopsy. Two types of metabolic behavior were therefore identified using F
      choline and F-FDG which corresponded to 2 different uptake patterns, that is,
      those of the prostate and lymphoma tumoral cell contingents.

PMID- 30300203
TI  - 18F-DCFPyL PET/CT in Oncocytoma.
AB  - A 76-year-old man with biochemical failure after primary radiotherapy for
      prostate cancer had no malignant disease detected on Tc-MDP bone scan and
      diagnostic CT. Prostate-specific membrane antigen (PSMA), a type II transmembrane
      glycoprotein, is overexpressed in prostate cancer cells. The PSMA-targeted F
      DCFPyL PET/CT demonstrated lymph node disease and photopenic defects in the left
      kidney associated with a cyst and biopsy-proven oncocytoma. Prostate-specific
      membrane antigen is expressed in the neovasculature of several solid tumors. It
      has been reported that PSMA expression is seen in approximately 50% of oncocytoma
      versus 76% of clear cell renal carcinomas. Biopsy confirmation is needed
      regardless of F-DCFPyL avidity.

PMID- 30300204
TI  - FDG PET/CT in a Case of Dural Amyloidoma.
AB  - Dural amyloidoma is an unusual presentation of central nervous system
      amyloidosis. A 49-year-old woman presented with 1-month history of repeated
      episodes of vertigo. Precontrast MRI showed dural thickening over right frontal
      convexity with signal intensity similar to white matter. Postcontrast T1-weighted
      images showed remarkable enhancement of the lesion. Dural amyloidoma was
      confirmed by partial resection of the lesion. The patient underwent no further
      treatment. A follow-up FDG PET/CT showed increased FDG uptake of the residual
      dural amyloidoma. This case indicates dural amyloidoma should be included in the
      differential diagnosis of abnormal FDG uptake in dural lesions.

PMID- 30300205
TI  - Quality and Safety in Healthcare, Part XLVII: Resilience and Burnout.
AB  - The ability to come back from challenges such as the many factors predisposing to
      burnout is resilience. Individual strategies to prevent and recover from burnout
      can be learned and practiced. This includes mindfulness, meditation, yoga,
      various stress reduction techniques, coaching, counseling, mentoring, discussions
      in small groups, workshops, and better work life balance. Other approaches
      include building a support network, taking care of one's personal health,
      pursuing narrative medicine, engaging in reflection, emphasizing positive
      psychology approaches including learned optimism, encouraging a growth mindset,
      and volunteering. This article will focus on the topic of resilience as it is
      related to burnout, and subsequent articles will discuss some of the strategies
      for prevention and recovery in detail.

PMID- 30300206
TI  - Unexpected Bone Metastases in 99mTc-Pertechnetate Scan of Recurrent Goiter.
AB  - A 68-year-old woman who underwent a thyroidectomy for bilateral goiter 20 years
      ago was referred to our department. The examination revealed a newly occurred
      thyroid nodule in the right central lobe. Unexpectedly the Tc-pertechnetate scan
      revealed several extrathyroidal foci right-sided supraclavicular, beside a cold
      thyroid nodule in the right lower lobe. Consecutive surgery and histology
      confirmed the suspected diagnosis of follicular thyroid cancer with multiple bone
      metastases. Whole-body scintigraphy performed after the following radioiodine
      therapy indicated disseminated osseous metastases.

PMID- 30300207
TI  - Hypermetabolism Caused by Seizure Mimicking Tumor Recurrence.
AB  - A 41-year-old man had a right frontal grade I glioma resection 17 years ago. He
      was tumor free since. However, 1 month ago, he presented with an uncontrollable
      seizure, which raised the possibility of recurrent tumor. The FDG PET/CT brain
      scan showed increased tracer uptake at the margin of the previous resected tumor,
      suggesting the possibility of tumor recurrence. However, on a repeat FDG PET
      brain scan confirmed by electroencephalography monitory as an interictal study,
      no elevated FDG uptake was revealed at this site. These results indicate that the
      elevated F-FDG activity on the original study was a result of seizure.

PMID- 30300208
TI  - Update on sinus disease in children with cystic fibrosis: advances in treatment
      modalities, microbiology, and health-related quality-of-life instruments.
AB  - PURPOSE OF REVIEW: There is a lack of consensus with regards to the diagnosis and
      treatment of sinus disease in children with cystic fibrosis. Here, we review
      literature from the past 18 months in order to highlight the way forward in this
      contentious field. RECENT FINDINGS: Most of the literature (from the past 18
      months) on sinus disease in pediatric cystic fibrosis focused on treatment
      approaches, bacteriology and immunology, and health-related quality-of-life
      (HRQOL) instruments. Quality studies have demonstrated that functional endoscopic
      sinus surgery (FESS) is as safe in children with or without cystic fibrosis; that
      the microbiology of the paranasal sinus in children with cystic fibrosis is
      different than that of their lungs; and, that HRQOL instruments may prove useful
      in determining sinonasal disease severity in children with cystic fibrosis.
      SUMMARY: Medical and surgical approaches appear to be viable in the treatment of
      sinonasal disease in pediatric cystic fibrosis; the microbiology and immunology
      of pediatric cystic fibrosis is proving more complex and nuanced than initially
      believed; and, HRQOL instruments show promise in reconciling differences between
      observable and clinically relevant sinus disease in pediatric cystic fibrosis
      patients.

PMID- 30300209
TI  - Velopharyngeal incompetence: role in paediatric swallowing deficits.
AB  - PURPOSE OF REVIEW: The purpose of this manuscript is to highlight the latest
      advances in diagnosis and management of velopharyngeal incompetence (VPI) as it
      pertains to swallowing deficits in children. This is timely and relevant as
      otolaryngologists are often amongst the first to diagnose and treat VPI. Although
      nasal regurgitation of a bolus is frequently transient, persistent problems can
      be associated with other swallowing problems and other significant medical
      problems. Furthermore, velopharyngeal incompetence has implications for speech
      production. RECENT FINDINGS: Persistent VPI associated with a swallowing deficit
      can be an isolated anomaly with or without a cleft palate or submucous cleft
      palate. VPI may be secondary to a cranial neuropathy, esophageal abnormality or
      associated with another airway anomaly, any of which may further contribute to
      dysphagia. Findings of additional anomalies may be suggestive of a syndrome.
      Workup should explore these potential causes. When velopharyngeal incompetence is
      associated with dysphagia, fiberoptic endoscopic evaluation of swallow (FEES) and
      videofluoroscopic swallow study (VFSS) can be helpful in diagnosis and
      management. The advantages and disadvantages of FEES and VFSS have been well
      delineated over the past few years. Similarly, nasopharyngoscopy and fluoroscopy
      are increasingly used in diagnosis and management of VPI that is associated with
      hypernasal resonance disorders. SUMMARY: Concurrent medical diagnoses or syndrome
      manifestations are often associated with or contribute significantly to the cause
      of dysphagia in children with VPI. As VPI can be a sign of brainstem vagal
      neuropathy, the clinician should investigate by imaging the CNS if other
      correlative symptoms of dysphagia and examination findings are present. Endoscopy
      is advocated for evaluation of vocal fold function. Fluoroscopy is best for
      further assessment of airway protection or safety of swallow. And, whenever
      indicated, additional workup is recommended to determine an underlying cause of
      the swallowing disorder.

PMID- 30300210
TI  - Recurrent respiratory papillomatosis: update 2018.
AB  - PURPOSE OF REVIEW: Recurrent respiratory papillomatosis (RRP) is the most common
      as well as the costliest benign airway neoplasm in the United States [Ivancic et
      al. (2018). Laryngoscope Investig Otolaryngol 3:22; Derkay (1995). Arch
      Otolaryngol Head Neck Surg 121:1386]. In addition, it is potentially deadly, with
      risk of airway obstruction as well as a 3-7% risk of malignant conversion
      [Schraff et al. (2004). Arch Otolaryngol Head Neck Surg 130:1039]. This review
      highlights exciting advancements over the past 1-2 years in scientific
      understanding of the pathophysiology, epidemiology, natural history, prevention,
      and treatment of this difficult disease. RECENT FINDINGS: Recent studies have
      yielded the following findings: The primary quality of life reduction that
      patients perceive is voice-related; the membranous vocal folds are the most
      frequently involved anatomic subsite in adult-onset RRP; there may be a
      correlation between laryngopharyngeal reflux, herpes simplex virus type 2, and
      adult-onset RRP; there has been a decline in RRP incidence in Australia following
      the implementation of a national vaccination program; addition of educational
      audiovisual aids assists in vaccine acceptance rates; preventive vaccination can
      be used as treatment for pediatric as well as adult RRP patients with
      demonstrable effects on antibody titers and reoperation rates; calreticulin
      linked DNA vaccines show promise in reducing the growth rate of human papilloma
      virus (HPV)11 E6/E7-expressing tumors in mice; injection of bevacizumab is
      associated with no adverse tissue affects; systemic bevacizumab is effective as a
      treatment for severe uncontrolled disease; pegylated interferon treatment is
      effective in select severe pediatric RRP disease; and finally, increased rates of
      programed death 1 T-lymphocyte infiltration and programed death-ligand 1
      expression are seen on both papilloma and infiltrating immune cells. SUMMARY: RRP
      is declining in incidence but remains a challenging disease to treat with great
      costs to patients, families, and the healthcare system. As the disease continues
      to be better understood, new frontiers are opening in treatment, particularly for
      severe or poorly controlled disease. Until the disease can be eradicated, it
      remains a vital area of research to help prevent new cases and treat afflicted
      patients.

PMID- 30300211
TI  - Vocal fold nodules in children.
AB  - PURPOSE OF REVIEW: Vocal nodules are a common presentation in children,
      representing the most common cause of dysphonia. RECENT FINDINGS: Children with
      siblings, ADHD, and of male sex are most likely to be affected. Female children,
      however, tend to have more likely progression into adolescence. Quality-of-life
      indices can aid in screening for vocal nodules whereas stroboscopy, and possibly,
      ultrasound are required for definitive diagnosis. SUMMARY: Management has not
      significantly changed over time and should begin with conservative behavioral and
      environmental modifications along with voice therapy in those more severely
      impacted. Though immediate outcomes vary somewhat depending on management
      direction, the overall prognosis seems to be good even with lack of intervention.
      It is most critical to ensure a definitive diagnosis, and offer management
      therapies that are appropriate for the level of impact the vocal nodules have on
      communication and voice production in the child.

PMID- 30300212
TI  - Recurrent laryngeal nerve reinnervation: is this the standard of care for
      pediatric unilateral vocal cord paralysis?
AB  - PURPOSE OF REVIEW: Ansa to recurrent laryngeal nerve reinnervation, otherwise
      known as a nonselective laryngeal reinnervation (NSLR), is growing in popularity
      for the management of pediatric unilateral neuronal vocal fold movement
      impairment (VFMI). In this chapter, we will review the current treatment options
      for neuronal VFMI and role that NSLR plays in the treatment algorithm. RECENT
      FINDINGS: In 2018, Bouhabel and Hartnick published a survey of fellowship trained
      pediatric otolaryngologists and found an increasing comfort level with NSLR.
      Respondents felt that NSLR resulted in favorable subjective and objective
      postsurgical voice outcomes. Furthermore, NSLR may decrease the risk of
      aspiration in children with neuronal VFMI. Although NSLR appears to work, the
      voice results are not perfect for all children. Further work is being done to
      understand which preoperative variables, such as age, time from injury, and preop
      laryngeal electromyography, may predict a better voice outcome. SUMMARY: A
      variety of treatment options exist for unilateral neuronal VFMI. Recent data and
      developments demonstrate the effectiveness of reinnervation as a potential first
      line surgical intervention in children with unilateral neuronal VFMI.

PMID- 30300213
TI  - The long and winding road.

PMID- 30300214
TI  - Predictors of antiretroviral adherence self-efficacy among people living with
      HIV/AIDS in a Canadian setting.
AB  - BACKGROUND: Sub-optimal adherence to antiretroviral therapy among people living
      with HIV/AIDS (PLWHA) who use illicit drugs remains an ongoing health concern.
      Although health outcomes associated with adherence self-efficacy have been well
      documented, there is dearth research exploring the predictors of this construct.
      This study sought to identify possible determinants of adherence self-efficacy
      among a cohort of PLWHA who use illicit drugs. METHODS: From December 2004 to May
      2014, we collected data from the AIDS Care Cohort to evaluate Exposure to
      Survival Services, a prospective cohort of adult PLWHA who use illicit drugs in
      Vancouver, Canada. We used multivariate generalized estimating equations (GEE)
      analyses to identify longitudinal factors independently associated with higher
      adherence self-efficacy. RESULTS: Among 742 participants, 493 (66.4%) identified
      as male and 406 (54.7%) reported white ancestry. In multivariate GEE analysis,
      older age at ART initiation (Adjusted Odds Ratio [AOR] = 1.02, 95% confidence
      interval [CI]: 1.00 - 1.03) and recent year of baseline interview (AOR = 1.08,
      95% CI: 1.05 - 1.11) were independently associated with higher adherence self
      efficacy, while homelessness (AOR = 0.78, 95% CI: 0.65 - 0.94); >= daily crack
      smoking (AOR = 0.81, 95% CI: 0.68 - 0.96); experienced violence (AOR = 0.82, 95%
      CI: 0.69 - 0.98), and childhood abuse (AOR = 0.75, 95% CI: 0.60 - 0.92) were
      negatively associated. CONCLUSIONS: These findings highlight the potential role
      that personal and contextual factors can play in predicting levels of ART
      adherence self-efficacy. Future research should seek to identify and validate
      strategies to optimize adherence self-efficacy.

PMID- 30300215
TI  - Two Surgeon Approach for Complex Spine Surgery: Rationale, Outcome, Expectations,
      and the Case for Payment Reform.
AB  - There is an increased trend in complex spine deformity cases toward a two
      attending surgeon approach, but the practice has not become widely accepted by
      payers. Multiple studies have shown that spine surgery complications increase
      with the duration of case, estimated blood loss, and use of transfusions, as well
      as in certain high-risk populations or those requiring three-column osteotomies.
      Dual-surgeon cases have been shown to decrease estimated blood loss, transfusion
      rate, surgical times, and therefore complication rates. Although this practice
      comes at an uncertain price to medical training and short-term costs, the
      patient's quality of care should be prioritized by institutions and payers to
      include dual-surgeon coverage for these high-risk cases. Because we enter an era
      where the value of spine care and demonstrating cost-effectiveness is essential,
      dual surgeon attending approaches can enhance these tenets.

PMID- 30300216
TI  - Optimizing Clinical Use of Biologics in Orthopaedic Surgery: Consensus
      Recommendations From the 2018 AAOS/NIH U-13 Conference.
AB  - Concern that misinformation from direct-to-consumer marketing of largely unproven
      "biologic" treatments such as platelet-rich plasma and cell-based therapies may
      erode the public trust and the responsible investment needed to bring legitimate
      biological therapies to patients have resulted in calls to action from
      professional organizations and governing bodies. In response to substantial
      patient demand for biologic treatment of orthopaedic conditions, the American
      Academy of Orthopaedic Surgeons convened a collaborative symposium and
      established a consensus framework for improving and accelerating the clinical
      evaluation, use, and optimization of biologic therapies for musculoskeletal
      diseases. The economic and disease burden of musculoskeletal conditions is high.
      Of the various conditions discussed, knee osteoarthritis was identified as a
      "serious condition" associated with substantial and progressive morbidity and
      emerged as the condition with the most urgent need for clinical trial
      development. It was also recognized that stem cells have unique characteristics
      that are not met by minimally manipulated mixed cell preparations. The work group
      recommended that minimally manipulated cell products be referred to as cell
      therapy and that the untested and uncharacterized nature of these treatments be
      clearly communicated within the profession, to patients, and to the public.
      Minimum standards for product characterization and clinical research should also
      be followed. A framework for developing clinical trials related to knee OA was
      agreed upon. In addition to recommendations for development of high-quality
      multicenter clinical trials, another important recommendation was that physicians
      and institutions offering biologic therapies commit to establishing high-quality
      patient registries and biorepository-linked registries that can be used for
      postmarket surveillance and quality assessments.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- 30300217
TI  - Management of Developmental Dysplasia of the Hip in Infants up to Six Months of
      Age: Intended for Use by General Pediatricians and Referring Physicians.
AB  - The American Academy of Orthopaedic Surgeons has developed the Appropriate Use
      Criteria (AUC) for the Management of Developmental Dysplasia of the Hip in
      Infants up to Six Months of Age: Intended for Use by General Pediatricians and
      Referring Physicians. Evidence-based information, in conjunction with the
      clinical expertise of physicians, was used to develop the criteria to improve
      patient care and obtain best outcomes while considering the subtleties and
      distinctions necessary in making clinical decisions. The Management of
      Developmental Dysplasia of the Hip in Infants up to Six Months of Age: Intended
      for Use by General Pediatricians and Referring Physicians AUC clinical patient
      scenarios were derived from indications typical of patients presenting with
      developmental dysplasia of the hip in clinical practice. The 24 patient scenarios
      and four treatments were developed by the Writing Panel, a group of clinicians
      who are specialists in this AUC topic. Next, a separate multidisciplinary, Voting
      Panel (made up of specialists and nonspecialists) rated the appropriateness of
      treatment of each patient scenario using a 9-point scale to designate a treatment
      as Appropriate (median rating, 7 to 9), May be Appropriate (median rating, 4 to
      6), or Rarely Appropriate (median rating, 1 to 3).

PMID- 30300218
TI  - Management of Developmental Dysplasia of the Hip in Infants up to Six Months of
      Age: Intended for Use by Orthopaedic Specialists.
AB  - The American Academy of Orthopaedic Surgeons has developed the Appropriate Use
      Criteria (AUC) for the Management of Developmental Dysplasia of the Hip in
      Infants up to Six Months of Age: Intended for Use by Orthopaedic Specialists.
      Evidence-based information, in conjunction with the clinical expertise of
      physicians, was used to develop the criteria to improve patient care and obtain
      best outcomes while considering the subtleties and distinctions necessary in
      making clinical decisions. The Management of Developmental Dysplasia of the Hip
      in Infants up to Six Months of Age: Intended for Use by Orthopaedic Specialists
      AUC clinical patient scenarios were derived from indications typical of patients
      presenting with developmental dysplasia of the hip in clinical practice. The 432
      patient scenarios and three treatments were developed by the Writing Panel, a
      group of clinicians who are specialists in this AUC topic. Next, a separate
      multidisciplinary, Voting Panel (made up of specialists and nonspecialists) rated
      the appropriateness of treatment of each patient scenario using a 9-point scale
      to designate a treatment as Appropriate (median rating, 7 to 9), May be
      Appropriate (median rating, 4 to 6), or Rarely Appropriate (median rating, 1 to
      3).

PMID- 30300219
TI  - Individual Treatment of Delayed Distal Biceps Tendon Rupture: Case Report and
      Literature Review.
AB  - INTRODUCTION: Complicated elbow injuries (elbow injuries with bone and soft
      tissue injury) with distal biceps tendon ruptures (DBTRs) are not uncommon. There
      are several treatment modalities in different situations of injuries. In this
      article, we reported 3 successful individual treatments of delayed DBTR with
      complicated elbow injuries. MATERIALS AND METHODS: Three cases of complicated
      elbow injuries treated between 2010 and 2016 were reviewed. The delayed DBTR
      cases were summarized and treated. Mayo Elbow Performance Score value, range of
      motion, and visual analog scale score were used to assess outcomes after a
      minimum follow-up of 12 months. RESULTS: All 3 patients were male, aged 47 to 54
      years (mean, 49.6 years). Patients received surgical treatments. After a mean
      follow-up of 13.7 months, in cases 1 and 2, Mayo Elbow Performance Score values
      improved by 50% and 100%, elbow flexion-extension arc were 115 degrees and 110
      degrees, pronation-supination arc were 130 degrees and 120 degrees. Arthrodesis
      case reported pain relief; visual analog scale score for pain was 0 to 1. No
      postoperative complications were observed, and all patients were satisfied with
      the results. CONCLUSIONS: Individual treatment is advised in DBTR with
      complicated elbow injuries. Secondary treatment of DBTR can achieve satisfactory
      results using individual strategies depending on patients' overall condition.

PMID- 30300220
TI  - Application of Concatenated Arterialized Venous Flaps in Finger Reconstruction.
AB  - Venous flaps from the distal volar forearm are said to be suitable flaps for
      finger reconstruction. The pliability of the forearm venous flap makes it easy to
      follow the curvature of the finger contour. The thickness of the flap makes it
      appropriate as a flap for finger resurfacing. Following the venous network at the
      palmar forearm, diverse patterns of the venous flaps can be designed. This
      article describes the use of a 2-concatenated paddle, flow-through arterialized
      venous flap design for simultaneous resurfacing of 2 separate defects on a single
      digit. A technique that can be used to reduce postoperative venous congestion
      will be highlighted in this article.

PMID- 30300221
TI  - Mechanical Dilation With a Nylon Monofilament for 0.1-mm Anastomoses.
AB  - Despite advances in supermicrosurgical techniques, the ability to anastomose
      vessels with a diameter of less than 0.2 mm remains limited. One of the reasons
      for this limitation is that the dilation methods currently available, such as
      inserting the tip of a microforceps into the lumen or topical application of a
      vasodilator such as papaverine hydrochloride or xylocaine spray, are not
      effective in very small vessels. To overcome this problem, we have developed a
      method whereby nylon monofilaments are placed inside the vessel lumen to act as a
      dilator. Using this method, a smaller nylon monofilament is inserted into the
      vessel as a guide before inserting a larger nylon monofilament as a dilator.
      After the smaller guide monofilament has been inserted, it is then much easier to
      insert another monofilament for dilation, even if it is a larger one. Using this
      method, even a vessel with a diameter of less than 0.1 mm could be dilated to
      greater than 0.2 mm. The dilator monofilament can also be used as an
      intravascular stent in the anastomosis. We have found that anastomosis of vessels
      with a diameter of less than 0.1 mm is possible using this method. In our
      experience, the immediate patency rate has been 100%. We believe mechanical
      dilation with a nylon monofilament is helpful for supermicrosurgery and even
      ultramicrosurgery.

PMID- 30300222
TI  - Readability, Suitability, and Complexity of Online Resources for Lower Extremity
      Reconstruction.
AB  - BACKGROUND: Surgical options for lower extremity reconstruction frequently
      include a decision between autologous free flap reconstruction and amputation.
      Patients rely on health education materials for information before making
      treatment decisions. This study evaluates the quality of online health
      information for lower extremity reconstruction. METHODS: We identified the top 10
      Web sites for "leg amputation" and "leg free flap reconstruction." Three
      validated tools were used to evaluate literacy demand of materials, including (1)
      the Simple Measure of Gobbledygook for readability; (2) the Peter Mosenthal and
      Irwin Kirsch readability formula for complexity of nonprose materials such as
      list, graphs, charts; and (3) the Centers for Disease Control and Prevention's
      Clear Communication Index (Index). Differences in mean between the 2 groups were
      compared using Student t test. RESULTS: Average Simple Measure of Gobbledygook
      reading grades approximated 12th-grade level and were similar between the 2
      groups. This is above the recommended level of sixth-grade health literature.
      Complexity scores for nonprose materials of these groups were within recommended
      range and corresponded to very low complexity at a fourth- to seventh-grade
      level. The Centers for Disease Control and Prevention index was higher for
      amputation literature compared with free flap reconstruction (70% vs 54%), but
      the difference was not statistically significant. CONCLUSIONS: Overall, online
      health resources for lower extremity amputation and free flap reconstruction do
      not meet the standard for quality and accessible health information. Free flap
      reconstruction resources are scarce and complex. Patients facing decisions about
      extremity reconstruction may not have appropriate online health resources
      available to them to make informed decisions.

PMID- 30300223
TI  - Cross-sectional Area Just Proximal to the Carpal Tunnel According to the Ulnar
      Variances: Positive Ulnar Variance and Carpal Tunnel Syndrome.
AB  - PURPOSE: We evaluated the relationship between the area around the distal
      radioulnar joint according to the ulnar variances and the cross-sectional area
      using magnetic resonance imaging (MRI) scans in this prospective study of
      patients with carpal tunnel syndrome (CTS). METHODS: From among a total of 243
      patients who had been diagnosed with CTS between March 2012 and February 2017 at
      our hospital, 41 patients with positive ulnar variance were enrolled in group 1.
      As control groups, 39 healthy volunteers who underwent MRI evaluations were
      included in group 2 (neutral ulnar variance) and group 3 (negative variance).
      Basic demographic data, including age, sex, and body mass index, were recorded
      for all 3 groups. An area encompassing the contents of carpal tunnel
      (nerves/tendons) was designated as area "A," and the area just beneath the
      subcutaneous fat was designated as area "B" at the levels of the lunate (L) and
      pisiform (P) on axial MRI. Ratios of these areas ("A/B at L" and "A/B at P") were
      evaluated in terms of their correlations with ulnar variance. RESULTS: Mean age,
      sex, and body mass index were not statistically different among the groups,
      respectively. Within each group, there was no difference between "A/B at L" and
      "A/B at P," respectively. When comparing the 3 groups, "A/B at L" and "A/B at P"
      were all significantly decreased in group 1 than in other groups. Regardless of
      the group, ulnar length negatively correlated with both "A/B at L" and "A/B at P"
      ratios. CONCLUSIONS: We found a positive relationship between decreased cross
      sectional area around the distal radioulnar joint and positive ulnar variance on
      radiologic investigation. These findings show the importance of variance in the
      positive ulna variance to the development of CTS.

PMID- 30300224
TI  - Comparative Study of Choke Vessel Reconstruction With Single and Multiple
      Perforator-Based Flaps on the Murine Back Using Delayed Surgery.
AB  - OBJECTIVE: Choke vessels, vascular anastomosis between adjacent angiosome, play
      an important role in flap expansion and survival. Here we established a flap
      model with single and multiple perforators to detect and compare the changes in
      choke vessels, discuss the effect of hemodynamics on the vascular morphology, and
      explore the underlying mechanism. METHODS: One hundred mice (7-8 weeks) were
      subjected to a "choke zone" surrounded by 4 perforators on their backs. Delayed
      surgery was performed by the ligation of 1, 2, or 3 perforators to establish flap
      models. The blood flow of the choke zone was measured by laser Doppler flowmetry
      preoperatively and 6 hours and 1, 3, 5, and 7 days. The morphological changes of
      choke vessels in the choke zone were observed by gross and histological analyses.
      Levels of angiogenesis-related markers such as endothelial nitric oxide synthase
      (eNOS), metalloproteinase 2, hypoxia-inducible factor 1alpha (HIF-1alpha), and
      intercellular adhesion molecule 2 (ICAM-2) were detected by Western blotting and
      enzyme-linked immunosorbent assay. RESULTS: Blood flow and microvascular count
      were obviously increased postoperatively and peaked and were maintained for 1
      week (P < 0.01). Meanwhile, the diameters of the choke vessels expanded. The eNOS
      level was increased at 7 days (P < 0.05); however, the enzyme-linked
      immunosorbent assay results showed that the HIF-1alpha and ICAM-2 levels were
      decreased at 7 days. CONCLUSIONS: (1) The delayed surgery that kept a single
      perforator had the greatest impact on the choke zone. (2) Changes in choke
      vessels were closely related to the shear stress caused by enhanced blood
      perfusion after surgery. (3) Choke vessel growth was regulated by eNOS,
      metalloproteinase 2, HIF-1alpha, and ICAM-2.

PMID- 30300225
TI  - The Influence of Patient Exposure to Breast Reconstruction Approaches and
      Education on Patient Choices in Breast Cancer Treatment.
AB  - BACKGROUND: The landscape of surgical and medical management and patient choices
      for breast cancer treatment changes as breast reconstruction and oncoplastic
      approaches improve and diversify. Increased access to breast reconstruction, in
      addition to patient education, influences the breast cancer patient. Therefore,
      the examination of the possible impact of reconstructive surgery on all stages of
      the breast cancer management per se seemed timely. METHODS: Plastic surgery
      consults were arranged for 520 new patients diagnosed with breast cancer (2012
      2016) including patients with noninvasive breast cancer but at high risk of
      further cancer development. To test the plastic surgery impact on patient choices
      regarding the management of the cancer, a subset of 90 patients was identified to
      test the plastic surgery impact on patient choices. These patients were referred
      to plastic surgery, following the first round of consultations by surgical and
      medical oncologists with only the preliminary oncological management plan
      defined. After a plastic surgery consultation, but prior to finalization of the
      overall oncological management plan, they were surveyed on the subject of
      modification of their personal choices and requests pertaining to their cancer
      management. RESULTS: In this subset of 90 patients 40 (44%) returned to their
      surgical or medical oncologist considering changes of the primary management plan
      after their plastic surgery consultation. Twenty-six (28%) ultimately altered
      their plan, and the following patient-driven changes were made: mastectomy as
      opposed to lumpectomy (18 patients [20%]), contralateral prophylactic mastectomy
      (11 patients [12%]), nipple/areola removal as opposed to nipple/areola sparing
      suggested by the oncologists (5 patients [6%]), oncoplastic breast reduction as
      part of lumpectomy (5 patients [6%]), and other modifications (3 patients [3%]).
      CONCLUSIONS: Decisions for altering the preliminary oncologic plan or choosing a
      specific alternative (eg, lumpectomy plus radiation vs mastectomy) resulted from
      patient education on (1) reconstructive options, (2) aesthetic pitfalls and
      results. and (3) their interfacing with the oncological outcomes. Ultimately,
      plastic surgeons influence the multispecialty breast cancer management and
      patient decision-making process. Therefore, oncological literacy for plastic
      surgeons is essential to provide state-of-the-art breast cancer care and
      avoidance of suboptimal patient decisions.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- 30300226
TI  - Pedicled Thoracodorsal Artery Perforator and Muscle-Sparing Latissimus Dorsi
      Flaps in the Axillary Reconstruction After Hidradenitis Suppurativa Excision:
      Functional and Aesthetic Issues.
AB  - BACKGROUND: Wide axillary reconstruction after hidradenitis suppurativa (HS)
      excision still represents a great challenge. Thoracodorsal artery perforator flap
      is one of the most reliable local reconstructive techniques. Although its anatomy
      and harvesting technique have been well described, specific reconstructive
      criteria still lack. The aim of this study was to help surgeons in planning
      axillary reconstruction on flaps based on the thoracodorsal artery. METHODS:
      Twelve patients affected by HS at Hurley stage III underwent wide "en block"
      excision and immediate reconstruction with 15 local thoracodorsal artery
      perforator flaps and 2 muscle-sparing latissimus dorsi flaps. A thorough chart
      review has been performed with preoperative and postoperative photographic
      documentations. Early and late complications have been analyzed. RESULTS: A total
      of 15 perforator flaps on thoracodorsal artery and 2 muscle-sparing latissimus
      dorsi flaps have been raised. The early complication rate was 29%, whereas the
      late complication rate was 35%. Except for one, all patients declared they were
      satisfied or highly satisfied from both aesthetic and functional points of view.
      Analyzing specific aspects, we have described several important details to
      consider for the reconstruction of the axilla. Through a retrospective analysis,
      we have classified HS axillary patients into 4 categories to better plan surgical
      reconstruction. CONCLUSIONS: Axillary reconstruction is still a plastic surgery
      challenge. Peculiar surgical details should be considered when approaching this
      area. This new classification may help young surgeons during the reconstructive
      phase.

PMID- 30300227
TI  - Maternal Tobacco Exposure and Development of Orofacial Clefts in the Child: A
      Case-Control Study Conducted in Pakistan.
AB  - INTRODUCTION: The purpose of this study was to evaluate the association between
      maternal tobacco exposure and development of orofacial clefts (OFCs) in the child
      in a Pakistani population. METHODS: A case-control study was conducted at the
      Cleft Hospital and Bashir Hospital in Gujrat, Pakistan, from December 2015 to
      December 2016. All new cases of OFC at the Cleft Hospital were included. Patients
      at Bashir Hospital younger than 3 years and without congenital malformations were
      selected as control subjects. Risk factors associated with OFC were identified
      through bivariate analyses. Multiple logistic regression was then performed to
      calculate adjusted odds ratios (ORs) of developing OFC according to various risk
      factors. RESULTS: The study included 297 patients with OFC and 131 control
      subjects. Upon univariable analysis, the following were associated with OFC:
      maternal tobacco exposure (P < 0.001), complications during pregnancy (P <
      0.001), maternal hypertension (P = 0.01), mother not on physician-recommended
      medications (P < 0.001), mother not receiving vaccinations (P < 0.001),
      consanguineous marriage (P < 0.001), and lower socioeconomic status (P < 0.001).
      Upon multivariable analysis, having a smoking parent (OR, 1.89; 95% confidence
      interval [CI], 1.10-3.26), complications during pregnancy (OR, 2.36; 95% CI, 1.43
      3.88), and consanguineous marriage (OR, 1.79; 95% CI, 1.13-2.85) were associated
      with increased odds of development of OFC; receiving vaccinations (OR, 0.31; 95%
      CI, 0.16-0.63) and higher socioeconomic status (OR, 0.20; 95% CI, 0.05-0.74) were
      protective. CONCLUSIONS: Patients with OFC were nearly twice as likely to have a
      parent who smokes as those without. Efforts to reduce tobacco consumption among
      prospective parents, such as perinatal tobacco cessation counseling programs,
      should be evaluated in this population.

PMID- 30300228
TI  - The Effects of Electrical Stimulation Parameters in Managing Spasticity after
      Spinal Cord Injury: A Systematic Review.
AB  - Controversial findings about the effects of neuromuscular electrical stimulation
      (NMES) and functional electrical stimulation (FES) in managing spasticity have
      been raised after spinal cord injury (SCI). A systematic review was conducted to
      identify the range of the stimulation parameters that may alleviate spasticity.
      Three independent reviewers searched Medline (PubMed), web of knowledge, Scopus,
      Cochrane Central, Virtual Health Library and Physiotherapy Evidence Database
      until January 2018. Inclusion criteria were applications of NMES/FES on the lower
      extremity muscles, stimulation parameters (frequency, pulse duration and
      amplitude of current) and measures of spasticity after SCI. The primary outcome
      was spasticity as measured by the Modified Ashworth Scale and the secondary
      outcome was spasticity assessed by other indirect measures. Twenty-three clinical
      and non-clinical trials were included with 389 subjects. NMES/FES provided
      reductions in spasticity by 45-60% with decrease in electromyography activity and
      increase in range of motion after SCI. The identified stimulation parameters were
      frequency of 20-30Hz, pulse duration of 300-350 MUs and amplitude of the current
      > 100 mA. NMES/FES provides an effective rehabilitation strategy in managing
      spasticity. However, a recommendation of the stimulation parameters cannot be
      accurately assumed due to high variability in the methodology, design and
      heterogeneity of the included studies.

PMID- 30300229
TI  - Physiotherapy in postinfection injury to cranial nerves III, IV, and VI: a case
      study.
AB  - The patient with bacterial infection sequelae in the form of damage to cranial
      nerves (CN) III, IV, and VI was followed-up. He had exhibited clinical and
      radiographic signs of paranasal sinusitis. Prior to his physiotherapy, the
      patient received standard treatment with natural and synthetic antibiotics and
      steroids. After acute signs of infection resolved without any functional
      improvement, the patient was referred to a rehabilitation unit to undergo
      neuromuscular re-education of the paralyzed extraocular muscles. Periorbital
      hydrocortisone iontophoresis and visuomotor exercises with intense ideomotor
      stimulation led to complete and rapid resolution of extraocular muscle paralysis
      and diplopia. Physiotherapy can be an effective treatment of choice after failed
      pharmacological treatment in patients with damage to CN III and VI. It has many
      theoretical advantages, including non-invasiveness and avoidance of first-pass
      metabolism of drugs administered systemically.

PMID- 30300230
TI  - A STIMULUS-RESPONSE FRAMEWORK TO INVESTIGATE THE INFLUENCE OF CONTINUOUS VERSUS
      INTERVAL WALKING EXERCISE ON SELECT SERUM BIOMARKERS IN KNEE OSTEOARTHRITIS.
AB  - OBJECTIVE: Compare changes in the concentration of serum biomarkers in response
      to continuous versus interval walking exercise in participants with knee
      osteoarthritis (OA). DESIGN: A two-phase sequential design. Twenty-seven
      participants with unilateral knee OA completed two separate treadmill walking
      sessions: 1) continuous 45-minute walking exercise and 2) three 15-minute bouts
      of walking exercise separated by 1-hour rest periods for a total of 45 minutes in
      an interval format. Participants reported their knee pain using the numeric pain
      rating scale and serum levels of biomarkers associated with tissue turnover
      [cartilage oligomeric matrix protein (COMP)], inflammation [Tumor necrosis factor
      alpha (TNF-alpha)] and pain [neuropeptide-Y (NPY)] were evaluated at baseline and
      every 15 minutes for both conditions. RESULTS: Continuous walking resulted in a
      cumulative increase in COMP concentration up to 45 minutes, whereas interval
      walking was associated with return of COMP concentrations back to baseline at 45
      minutes. There were no significant changes in TNF-alpha and NPY concentration
      during walking. There was a significant increase in pain compared to baseline in
      the continuous walking regimen only. CONCLUSION: Incorporating rest breaks in
      walking regimens may impact the potential deleterious effects of longer
      continuous bouts on the knee joint as well as limit pain during exercise.

PMID- 30300231
TI  - Measuring the Impact of Research Using Conventional and Alternative Metrics.
AB  - Bibliometrics utilize statistical methods to measure the scholarly impact of
      publications. Bibliometrics are categorized as conventional metrics (CM) or
      alternative metrics (AM). CM have often been considered the standard to measure
      the impact of publication-related scholarship. With the growing popularity of
      social media (SoMe) and ease of instantaneous distribution of information
      globally, AM have become an important complementary measure of scholarly
      activity. Bibliometrics may provide a standard performance measurement that may
      be used for tenure and/or promotion among academic institutions. The alternative
      metric industry has shown considerable growth with increasingly improved
      algorithms working towards standardization. Together, CM and AM may
      synergistically complement each other to provide an accelerated translation from
      research to clinical care that may lead to tremendous benefits in patients. All
      physicians and other healthcare professionals should receive training in
      bibliometrics and understand the potential impact of professional social media
      use.

PMID- 30300232
TI  - Electrical stimulation in the treatment of hemiplegic shoulder pain: a meta
      analysis of randomized controlled trials.
AB  - : OBJECTIVETo determine the effect of electrical stimulation (ES) in the
      treatment of hemiplegic shoulder pain (HSP).DESIGNEight databases were
      systematically searched for randomized controlled trials (RCTs) with a treatment
      duration of at least two weeks comparing ES with sham stimulation or no
      stimulation for patients with HSP. Shoulder pain on the hemiplegic side after
      stroke at baseline was required at study selection. The overall effects of ES
      were calculated using a meta-analytic method. RESULTS: Six studies were included.
      The pooled data indicated that ES may have a positive effect for patients with
      HSP on pain reduction (n=193; SMD [standardized mean difference] = -1.89; 95% CI
      [-3.05, -0.74]) and pain-free external rotation (PFER) (n=164; WMD [weighted mean
      difference] = 18.92; 95% CI [7.00, 30.84]). Meta-analysis also showed better
      recovery of activities of daily living (ADL) independence in patient groups
      receiving ES (n=167; WMD = 8.96; 95% CI [5.26, 12.66]). CONCLUSIONS: ES may be an
      effective pain management methodology for hemiplegic shoulders and may contribute
      to pain-free range of external rotation as well as ADL recovery. However, these
      results should be interpreted with caution, given the low number of selected
      studies and risk of potential bias.

PMID- 30300233
TI  - Is Occupational Therapy After Hip Fracture Surgery Effective in Improving
      Function? A Systematic Review and Meta-analysis of Randomized Controlled Studies.
AB  - OBJECTIVES: This study is aimed to evaluate whether occupational therapy (OT)
      improves activities of daily living (ADL) and overall physical functioning of
      patients after hip fracture surgery (HFS).PubMed-Medline, Embase, and Cochrane
      Library databases.We searched for randomized controlled trials comparing OT with
      comprehensive postoperative care (without OT) after HFS. A pairwise meta-analysis
      using fixed- and random-effects models was performed. The primary outcome of
      interest was performance of ADL assessed in any manner. The secondary outcomes
      were other functional parameters: 1) physical function; 2) health perception and
      emotion; and 3) fall occurrence. Effect sizes were computed as standardized mean
      differences (SMDs) with 95% confidence intervals (CIs). RESULTS: Five randomized
      controlled trials including a total of 524 participants were retrieved. There was
      a trend towards improvement in ADL, physical function, and fall occurrence, these
      changes were not significant. However, health perception and patient emotions
      improved significantly in the OT group (SMD=0.391; 95% CI, 0.104-0.678; p=0.008).
      CONCLUSION: OT after HFS seems to improve overall function. Indeed, the positive
      effects of OT on health perception and emotions were evident. Therefore, OT can
      be suggested in comprehensive rehabilitation programs after HFS.

PMID- 30300234
TI  - Dorsal Scapular Neuropathy as a Rare Cause of Complex Regional Pain Syndrome: A
      Reappraisal on Ultrasound Imaging and Guidance for Recalcitrant Pain.

PMID- 30300236
TI  - Anal Sex Is More Common Than Having a Twitter Account in the United States.

PMID- 30300237
TI  - Computerized exposure therapy for Spider Phobia: Effects of cardiac timing and
      interoceptive ability on subjective and behavioral outcomes.
AB  - OBJECTIVE: Spider phobia is a common form of anxiety disorder for which exposure
      therapy is an effective first-line treatment. Motivated by the observed
      modulation of threat processing by afferent cardiac signals; we tested the
      hypothesis that interoceptive information concerning cardiovascular arousal can
      influence the outcomes of computerised exposure therapy for spider phobia.
      METHOD: Fifty-three normal healthy participants with high spider phobia scores
      underwent one of three modified computerised exposure protocols, defined by the
      timing of exposure to brief spider stimuli within the cardiac cycle: Systole
      (during afferent baroreceptor firing); Diastole (during baroreceptor-quiescent
      interbeat interval); Random (non-contingent on cardiac cycle). Outcomes were
      judged on phobic and anxiety measures and physiological data (skin conductance).
      Subjects were also rated on interoceptive accuracy. RESULTS: Mancova analysis
      showed that timing group affected the outcome measures (F(10,80)=2.405, p=0.015)
      and there was a group interaction with interoception ability (F(15,110)=1.808,
      p=0.045). Subjective symptom reduction (SPQ) was greatest in the Systolic group
      relative to the other two groups (Diastolic (t=3.115, ptukey=0.009); Random
      (t=2.438, ptukey=0.048), with greatest reductions in those participants with
      lower interoceptive accuracy. Behavioural aversion (BAT) reduced more in cardiac
      contingent groups than the non-contingent (Random) group (Diastolic (t=3.295,
      ptukey=0.005); Systolic (t=2.602, ptukey=0.032). Physiological (SCR) responses
      remained strongest for spider stimuli presented at cardiac systole. CONCLUSION:
      Interoceptive information influences exposure benefit. The reduction in the
      subjective expression of fear/phobia is facilitated by 'bottom-up' afferent
      signals; while improvement in the behavioural expression is further dependent on
      'top-down' representation of self-related physiology (heart rhythm). Individual
      interoceptive differences moderate these effects, suggesting means to personalise
      therapy.

PMID- 30300238
TI  - Bereavement, self-reported sleep disturbances and inflammation: Results from
      Project HEART.
AB  - OBJECTIVE: Spousal bereavement is linked to increased mortality and morbidity
      from inflammatory conditions. It also has a significant impact on sleep
      disturbances. Evidence from experimental studies indicates that chronic stress
      may prime individuals to have an exaggerated inflammatory response to acute
      stress. In this study, we examined the association between self-reported sleep
      disturbances and inflammation after adjusting for depressive symptoms, and
      determined whether this association varies by bereavement status (bereaved
      individuals vs. controls). METHODS: Participants included 54 bereaved individuals
      and 47 controls with a mean age of 67.12 (SD=12.11). Inflammation was measured
      using C-reactive protein (CRP). Self-reported sleep disturbances were measured
      using the Pittsburgh Sleep Quality Index (PSQI). Depressive symptoms were
      measured using the Center for Epidemiologic Studies Depression Scale (CES-D).
      RESULTS: Sleep disturbances were not associated with elevated levels of CRP in
      the overall group (B=0.030, standardized beta=0.122, 95% Confidence Intervals
      [CI]=-0.027 - 0.087, p=0.299) after adjusting for depressive symptoms. Results
      indicated, however, that bereavement moderated the association between
      inflammation and sleep disturbances (B=0.104, beta=0.517, 95% CI=0.009 - 0.198,
      p=0.032). Stratified analyses demonstrated that these associations differed
      across groups. Associations were significant among bereaved individuals (B=0.104,
      beta=0.406, 95% CI=0.013 - 0.196, p=0.026) and not controls (B=-0.016, beta=
      0.066, 95% CI=-0.096 - 0.065, p=0.690). CONCLUSIONS: These findings provide
      preliminary evidence that bereavement moderates the association between self
      reported sleep disturbances and inflammation. Future studies should examine the
      course of sleep disturbances following bereavement and establish whether
      objective sleep has differential associations with inflammation among bereaved
      adults.

PMID- 30300239
TI  - Multiple sclerosis: clinical aspects.
AB  - PURPOSE OF REVIEW: Multiple sclerosis is a chronic, predominantly immune-mediated
      disease of the central nervous system, and one of the most common causes of
      neurological disability in young adults globally. This review will discuss the
      epidemiology, diagnosis, disease course, and prognosis of multiple sclerosis and
      will focus on recent evidence and advances in these aspects of the disease.
      RECENT FINDINGS: Multiple sclerosis is increasing in incidence and prevalence
      globally, even in traditionally low-prevalence regions of the world. Recent
      revisions have been proposed to the existing multiple sclerosis diagnostic
      criteria, which will facilitate earlier diagnosis and treatment in appropriate
      patients. Classifying multiple sclerosis into distinct disease phenotypes can be
      challenging, and recent refinements have been proposed to clarify existing
      definitions. The prognosis of multiple sclerosis varies substantially across
      individual patients, and a combination of clinical, imaging, and laboratory
      markers can be useful in predicting clinical course and optimizing treatment in
      individual patients. SUMMARY: A number of recent advances have been made in the
      clinical diagnosis and prognostication of multiple sclerosis patients. Future
      research will enable the development of more accurate biomarkers of disease
      categorization and prognosis, which will enable timely personalized treatment in
      individual multiple sclerosis patients.

PMID- 30300240
TI  - Are molecular subgroups of medulloblastomas really prognostic?
AB  - PURPOSE OF REVIEW: Medulloblastoma is no more a unique disease. Clinical and
      biologic classification used so far are challenged by molecular
      classification(s). Following the consensus article that described four molecular
      groups of medulloblastoma in 2012, several articles in 2017 provided more
      relevant classifications that may impact on further clinical trial design. RECENT
      FINDINGS: Though wingless (WNT) and sonic hedgehog (SHH) are defined by the
      activation of their respective pathways, the age and type of activation define
      various subgroups with specific features and outcome. Groups 3 and 4 remain ill
      defined. The whole population of medulloblastoma may be divided in 12 subgroups:
      WNTalphabeta, SHHalphabetagammadelta, group 3alphabetagamma and group
      4alphabetagamma. The paediatric population may be divided in seven subgroups:
      WNT, SHH of infants and children, and low-risk and high-risk groups 3 and 4. SHH
      of infants may be divided as iSHH-I vs. iSHH-II that have different prognosis.
      Moreover, specific drivers of groups 3 and 4 were reported. SUMMARY: These
      findings have and will have direct implications on the conception of clinical
      trials. Low-risk groups will benefit from less toxic therapies, and high-risk
      groups will benefit from targeted therapies.

PMID- 30300241
TI  - Is whole-brain radiotherapy still a standard treatment for primary central
      nervous system lymphomas?
AB  - PURPOSE OF REVIEW: In primary central nervous system lymphomas (PCNSL), optimal
      therapy remains to be established, and the role of whole-brain radiotherapy
      (WBRT) is a matter of debate. With radiation alone, transient responses and
      clinical improvement are frequent, but long-term disease control is exceptional.
      WBRT has been considered possible consolidation therapy after high-dose
      methotrexate (HDMTX)-based initial chemotherapy. This strategy has been
      questioned due to a high risk of delayed neurotoxicity after combined treatment.
      This review analyses the current role of WBRT in PCNSL. RECENT FINDINGS: Neither
      in retrospective analyses nor in randomized trials, an overall survival benefit
      with WBRT in addition to HDMTX-based initial chemotherapy could be found. On the
      other hand, a recent randomized trial did not show superiority of consolidation
      with high-dose chemotherapy followed by autologous stem-cell transplantation to
      consolidation WBRT after initial HDMTX-based polychemotherapy. This finding,
      however, is probably due to an intense initial therapy and to a small number of
      patients having reached consolidation and randomization to WBRT vs. high-dose
      chemotherapy followed by autologous stem-cell transplantation. SUMMARY: The
      current role of WBRT in PCNSL is confined to patients who cannot tolerate
      chemotherapy or have failed it. WBRT should not routinely be used for
      consolidation of HDMTX-based chemotherapy due to lack of evidence of efficacy as
      additional treatment and due to a high risk of neurotoxicity.

PMID- 30300242
TI  - Editorial: Hot Topics in Neuro-Oncology.

PMID- 30300243
TI  - Mycobacterium chimaera infections following cardiac surgery in Italy: results
      from a National Survey Endorsed by the Italian Society of Cardiac Surgery.
AB  - AIMS: A global outbreak of Mycobacterium chimaera infections following cardiac
      surgery and linked to contaminated heater-cooler units (HCUs) is currently
      ongoing. Neither the status of this outbreak in Italy nor the mitigation
      strategies adopted by adult cardiac surgery units (ACSUs) are currently known. In
      2017, the Italian Society of Cardiac Surgery launched a national survey among the
      Italian ACSU to shed some light on this issue. METHODS: In Italy, there are 90
      ACSUs across 20 regions. From May to November 2017, these ACSUs were surveyed
      collecting data on patients diagnosed with MC infections, ACSU workload, HCU
      models in use and control measures adopted in the operatory room. RESULTS: The
      response rate was 87.8%. The median number of cardiac procedures at each ACSU was
      450/year [interquartile range (IQR) 350-650 procedures/year], and nationally, the
      number of procedures/year exceeded 40k. In Italy, seven patients with M. chimaera
      infections following cardiac procedures have been reported since 2015: all had
      aortic or valvular surgery as the first procedure; the median latency between the
      first operation and the infection was 2 years (IQR 2-3.25). Mortality for
      patients requiring redo cardiac surgery was 50%. M. chimaera infections risk was
      0.4-1 patient every 1000 cardiac procedures. The most common HCU model in Italy
      is the 3T HCU (70.9%). The most common control measures adopted included
      implementing new HCU disinfection protocols, using sterile or filtrated water in
      the HCU and displacing HCU fans away from the patient: HCU replacement and
      microbiology testing were instead infrequent. CONCLUSION: In Italy, the risk of
      contracting M. chimaera infections and the mortality reported are in line with
      other European countries, but significant heterogeneity exists on the mitigation
      strategies adopted to prevent further M. chimaera inoculations, suggesting the
      development of national guidelines.

PMID- 30300244
TI  - Results of new-generation intrapericardial continuous flow left ventricular
      assist devices as a bridge-to-transplant.
AB  - AIMS: We analysed the outcomes with the use of a new-generation continuous-flow
      left ventricular assist device (CF-LVAD) as a bridge-to-transplant (BTT).
      MATERIALS AND METHODS: We included all patients implanted with an
      intrapericardial CF-LVAD as BTT, between January 2012 and December 2016. Primary
      outcomes were overall survival, survival on waiting list and postheart transplant
      (HTx) survival. The outcomes after HTx were compared with those of a contemporary
      cohort of patients transplanted without previous CF-LVAD (No-LVAD group, n = 73).
      RESULTS: We included 53 patients with a median age of 52 years (interquartile
      range: 43-59 years). Seventy-two percent were in INTERMACS profile 1-2 before
      implant; all entered the HTx waiting list after receiving the CF-LVAD. HTx was
      performed in 42 (79%) cases (LVAD group). Overall estimated survival (considering
      both pre-HTx and post-HTx) was 89% [95% confidence interval (CI) 81-98%] at 1
      year and 80% (CI 70-92%) at 2 years. The estimated survival on waiting list was
      91% (CI 80-100%) at 6 months, whereas the 1-year estimated post-HTx survival was
      88% (CI 79-98%). The Kaplan-Meier curves of survival after HTx of LVAD versus No
      LVAD group were comparable (log-rank P = 0.54), as well as the rates of post-HTx
      adverse events. A multivariable model of survival after HTx, accounting for the
      most relevant patient characteristics, identified LVAD use as a significant
      protective factor [LVAD versus No-LVAD hazard ratio 0.22 (CI 0.06-0.91)].
      CONCLUSION: The use of new-generation intrapericardial CF-LVADs as a BTT
      resulted, in our series, in satisfactory pre-HTx and post-HTx outcomes.

PMID- 30300245
TI  - Tenodesis of the Ulnotriquetrum Ligament to the Fovea for a Triangular
      Fibrocartilage Complex Tear.
AB  - We developed a novel procedure to treat a triangular fibrocartilage complex
      (TFCC) foveal tear, namely tenodesis of the ulnotriquetrum ligament (UTL) to the
      fovea. We attempted to reestablish the tension of the palmar radioulnar ligament
      by the procedure specifically in cases with palmar radius instability relative to
      the ulna. We used a palmar surgical approach to expose the palmar aspect of TFCC
      in which the ulnocarpal ligament merges with the palmar radioulnar ligament. UTL
      was distally excised at a 4 mm width from the triquetrum without disrupting its
      ligamentous connection to the palmar radioulnar ligament proximally. We pulled
      out the distal UTL through the bone tunnel from the fovea to ulnar neck. The UTL
      graft was fixed to the fovea with an interference screw. In 13 cases, this
      procedure effectively decreased ulnar wrist pain, improved distal radioulnar
      joint instability, and restored wrist motion and grip strength.

PMID- 30300246
TI  - Surgical Management of the Posttraumatic Stiff Elbow: A Step-Wise Algorithm for
      Open Osteocapsular Release.
AB  - Posttraumatic elbow stiffness is common with the primary indication for
      contracture release being limited motion that affects functional activities which
      has not adequately improved after intensive therapy and rehabilitation.
      Preoperative evaluation focuses on the history of previous nonoperative and/or
      operative treatment, physical exam with particular attention paid to the status
      of the ulnar nerve, and imaging consisting of radiographs and computed
      tomography. There are multiple intrinsic and extrinsic causes of posttraumatic
      contracture. In general, limitation of motion in one direction can be attributed
      to a mechanical block and/or opposing contracture or tightness. Open elbow
      contracture release has been shown to improve motion, patient health status and
      disability scores with the specific surgical approach based upon the contracture
      pathology and surgeon preference. A step-wise algorithm is presented for open
      osteocapsular release. An anterior and posterior release is performed first
      through a lateral approach with the addition of a medial approach if ulnar nerve
      dysfunction exists or inadequate release has been obtained from the lateral
      approach. A previous posterior incision can be utilized by raising full thickness
      flaps. After release, gentle manipulation is performed and intraoperative
      stability is assessed with stress testing under fluoroscopy. Postoperatively,
      pain is managed with an in-dwelling nerve catheter and rehabilitation commences
      immediately. Significant improvement in range of motion can be expected with
      adequate surgical release and postoperative rehabilitation.

PMID- 30300247
TI  - Therapeutic Management of the Posttraumatic Stiff Elbow After Open Osteocapsular
      Release.
AB  - Arthrofibrosis is an inevitable consequence of elbow trauma that oftentimes
      requires surgical release to restore range of motion and function. Although the
      surgical procedure for elbow osteocapsular release can result in marked
      improvement in elbow motion, postrelease rehabilitation is paramount to
      maintaining and even improving the gains achieved in surgery. There are a variety
      of rehabilitation protocols and modalities that can be implemented that can be
      divided into an early versus late stage of rehabilitation after surgery.
      Irrespectively, patient ownership in the rehabilitative process and effective
      communication between surgeon and therapist are integral in achieving successful
      outcomes.

PMID- 30300248
TI  - An Eco-conscious Alternative Material for Splinting in Hand Surgery.

PMID- 30300249
TI  - Pharmacogenomics Testing for Postoperative Pain Optimization Before Total Knee
      and Total Hip Arthroplasty.

PMID- 30300250
TI  - Team Approach: Perioperative Optimization for Total Joint Arthroplasty.

PMID- 30300251
TI  - Effects of herbs and spices on blood pressure: a systematic literature review of
      randomised controlled trials.
AB  - : Hypertension is a major risk factor for cardiovascular disease, affecting 1
      billion people worldwide. Literature suggests some herbs and spices have
      cardiovascular benefits, such as decreasing blood pressure; yet evidence is
      inconsistent. This article reviewed randomized controlled trials investigating
      effects of herbs and spices on blood pressure in normotensive, pre-hypertensive
      and hypertensive participants. Ovid Medline, Embase, Biological abstracts, CINAHL
      and Cochrane Collaboration were systematically searched. After inclusion and
      exclusion criteria were applied, nine articles were included for analysis.
      Overall, three of the nine studies reported statistically significant results,
      including one of the two studies on hypertensive participants and two of the six
      studies on pre-hypertensive participants. The remaining study was conducted on
      normotensive participants and reported no change in blood pressure. There is
      evidence to suggest certain herbs and spices can reduce blood pressure in a
      hypertensive and pre-hypertensive population and may not induce hypotension in a
      normotensive population.

PMID- 30300252
TI  - Combined impact of risk factors on the subsequent development of hypertension.
AB  - OBJECTIVES: This study aimed to develop a cumulative score composed of seven risk
      factors: age, resting heart rate, overweight or obesity, dyslipidemia,
      hyperuricemia, impaired glucose regulation, and impaired estimated glomerular
      filtration rate (eGFR), to evaluate the risk of new-onset hypertension. METHODS:
      We retrospectively conducted a cohort study in 23 665 participants free from
      hypertension at baseline, who attended at least two annual health examinations
      between 2011 and 2016. We defined hypertension as SBP of 140 mmHg or less and/or
      DBP of at least 90 mmHg, according to the 2010 Chinese guidelines for the
      management of hypertension. We computed a composite, individual-level cumulative
      score incorporating all seven risk factors (no = 0 point; yes = 1 point; total
      range 0-7 points). Cox regression was used to analyze the association between
      cumulative score and risk of hypertension. RESULTS: A total of 2305 participants
      developed hypertension during a median follow-up period of 3.6 years. Compared
      with participants with 0 points, the adjusted hazard ratios (95% confidence
      intervals) for the development of hypertension for those with 2, 3, and at least
      4 points were 1.61 (1.29-2.02), 2.05 (1.64-2.57) and 2.77 (2.22-3.46),
      respectively (P trend < 0.001). This association was present after adjustment for
      sex and baseline blood pressure. CONCLUSION: Age, resting heart rate, overweight
      or obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and
      impaired eGFR were associated with significant risk of new-onset hypertension and
      when combined there was an accumulation of risk.

PMID- 30300253
TI  - A Pediatric Nasogastroscope Facilitates Colorectal Endoscopic Stenting.
AB  - PURPOSE: Endoscopic placement of self-expandable metal stents (SEMSs) to relieve
      malignant colorectal obstruction has been widely accepted in clinical practice.
      Despite increasing experience, early and late complications occur with an
      incidence ranging from 4% to 20%. MATERIALS AND METHODS: We have adopted a
      modification in the technique. A pediatric nasogastroscope (4.8 mm in diameter)
      has been used to pass the obstruction. It is possible to have a direct vision of
      the anatomy and pathology, and to pass the guidewire above the obstruction,
      through the nasogastroscope, under direct vision. Fluoroscopy was also used to
      follow the course of the guidewire and deployment of the stent. RESULTS: Early
      and late complications have been reduced with the new technique. CONCLUSIONS: In
      the most recent experience of 64 patients, early and late complications have been
      reduced significantly. This new technique reduces radiation exposure by 70% for
      the patients and for the operators.

PMID- 30300254
TI  - Is Prophylactic Steroid Treatment Mandatory for Subclinical Cushing Syndrome
      After Unilateral Laparoscopic Adrenalectomy?
AB  - OBJECTIVE: This study aimed to provide rational guidelines for patients with
      subclinical Cushing syndrome (SCS), who are undergoing laparoscopic
      adrenalectomy, in order to avoid the risk of overtreatment. METHODS: A total of
      59 patients diagnosed with SCS caused by unilateral adrenal adenoma, who
      underwent laparoscopic adrenalectomy from 2010 to 2017, were included into the
      study. These patients did not receive prophylactic steroid treatment. After
      discharge, patients with adrenal insufficiency (AI) were treated with
      glucocorticoid. Then, cortisol levels were reevaluated at three months after
      surgery by morning serum cortisol. RESULTS: No severe perioperative complications
      occurred. After unilateral laparoscopic adrenalectomy, no patient developed AI
      and was readmitted. In the first week after surgery, 10 patients (16.9%) received
      steroid therapy at the clinic because of mild symptoms of AI. The probability of
      developing AI was greater in patients with 1-mg dexamethasone midnight
      suppression test (1 mg-DST) >5 MUg/dL than patients with mg-DST ranging within
      1.8 to 5.0 MUg/dL (P=0.042). The initial dose of hydrocortisone was 20.00+/-6.67
      mg/d (range, 10 to 30), and the duration of treatment was 6.90+/-3.51 weeks
      (range, 3 to 12 wk). At three months after surgery, morning cortisol was >5
      MUg/dL in all patients. CONCLUSIONS: After laparoscopic adrenalectomy, the
      probability of AI is small in patients with adrenal SCS, and the symptoms of AI
      were mild. Meanwhile, the HPA axis rapidly recovered. Therefore, prophylactic
      steroid treatment is not mandatory. Given that AI is more frequent in patients
      with higher cut-offs of 1 mg-DST, a more precise definition of SCS is necessary
      to better manage these patients.

PMID- 30300255
TI  - Complete Jejunal Transection After Blunt Abdominal Trauma: A Case Report.
AB  - INTRODUCTION: Isolated complete transection of the small bowel is extremely rare
      in blunt abdominal trauma. If it occurs, it is often associated with high-energy
      impact, as seen in motor vehicle accidents and falls from heights. In this case,
      a trivial trauma due to a handlebar injury caused a complete transection of the
      middle jejunum. CASE PRESENTATION: A 47-year-old man walked into the emergency
      department with moderate abdominal pain ~10 hours after a fall on to a bicycle's
      handlebar from a standing position. A bedside ultrasound showed minimal amount of
      free fluid and a following performed computed tomographic scan indicated an
      edematous loop of small bowel with diminutive amount of extraluminal air,
      suggesting small bowel perforation. Because of the absence of abdominal
      peritonism in a hemodynamically stable patient, a conservative treatment and
      surveillance was established. In the follow-up, the patient suddenly developed
      severe abdominal pain with now clear signs of peritonism. An emergency
      laparoscopy showed a complete transection of the middle jejunum. A primary
      anastomosis was performed. The patient had an uneventful recovery and was
      discharged after 7 days. CONCLUSIONS: Even seemingly trivial blunt abdominal
      traumas can cause complete transection of the small bowel, as shown in this case.
      Patients with blunt abdominal trauma need to be reviewed frequently by an
      experienced clinician. Diagnostic laparoscopy attaches a great importance to
      early detection and treatment of small bowel injuries. The mechanical pattern of
      the injury seems to be more important than the energy of the impact itself.

PMID- 30300256
TI  - Obstructive Sleep Apnea in Neuro-Ophthalmology.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a common pulmonary disorder with
      many systemic sequelae. Its association with diseases seen in neuro-ophthalmology
      is being increasingly recognized. Treatment of OSA with continuous positive
      airway pressure (CPAP) may reverse the pathology in some eye diseases. EVIDENCE
      ACQUISITION: We conducted a search of the literature using the Ovid Medline
      database and Google Scholar, focusing on articles that explored the association
      between OSA and ophthalmic conditions. These included hypertensive retinopathy,
      diabetic retinopathy, central serous retinopathy (CSR), retinal vein occlusion
      (RVO), nonarteritic anterior ischemic optic neuropathy (NAION), glaucoma,
      idiopathic intracranial hypertension (IIH), papilledema, and stroke. RESULTS:
      There is evidence of an independent association between OSA, and both
      hypertension and Type 2 diabetes mellitus, as well as the retinopathy associated
      with each disease. Evidence also suggests a link between OSA and CSR, NAION, and
      stroke. The evidence remains controversial or insufficient for convincing
      causative association with RVO, glaucoma, and IIH. However, in patients
      presenting with CSR, and IIH, underlying OSA is a common finding. CPAP reverses
      some pathological changes, but the evidence is limited. CONCLUSIONS: OSA is
      associated with many diseases seen in neuro-ophthalmology clinics. More studies
      are required to assess the real ability of CPAP to reverse pathological changes.
      Ophthalmologists can screen for undiagnosed OSA in patients presenting with
      certain eye diseases.

PMID- 30300257
TI  - Risk Factors for Fellow Eye Involvement in Nonarteritic Anterior Ischemic Optic
      Neuropathy.
AB  - BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAION) is the most
      common acute optic neuropathy in individuals older than 50 years. Demographic,
      ocular, and systemic risk factors for NAION have been identified, and we sought
      to determine which, if any, of these factors also increase risk of NAION in the
      fellow eye. METHODS: We performed a retrospective chart review of patients with
      "ischemic optic neuropathy" (based on International Classification of Disease
      [ICD] codes) seen at a single eye center between 2007 and 2017. Patients who met
      diagnostic criteria for unilateral NAION without fellow eye optic neuropathy at
      diagnosis were included. Demographic information, ocular comorbidities, and
      systemic diagnoses were recorded, in addition to whether the fellow eye developed
      NAION during the follow-up period. Univariate and multivariate Cox proportional
      hazard regression were used to calculate hazard ratios (HRs) for fellow eye
      involvement. RESULTS: Three hundred eighteen patients were identified by ICD
      codes, and 119 were included in the study. Twenty-nine (24%) patients developed
      NAION in the fellow eye over the mean follow-up period of 3.6 years (range: 1
      month-11 years). Significant risk factors for fellow eye NAION included the
      presence of bilateral optic disc drusen (ODD, HR 2.78, 95% confidence interval
      [CI] 1.12-6.90, P = 0.02) and noncompliance with continuous positive airway
      pressure (CPAP) in patients with moderate-to-severe obstructive sleep apnea (HR
      4.50, 95% CI 1.79-11.3, P = 0.0015). CONCLUSIONS: Bilateral ODD and noncompliance
      with CPAP when indicated are associated with increased risk of NAION in the
      fellow eye. Patients with these risk factors should be counseled on the
      potentially devastating visual consequences of bilateral NAION, and compliance
      with CPAP should be stressed when appropriate.

PMID- 30300258
TI  - Experience with definitive instrumented final fusion after posterior-based
      distraction lengthening in patients with early-onset spinal deformity: single
      center results.
AB  - Limited reports exist with regard to clinical and radiographic details of
      patients with early-onset spinal deformity (EOSD) undergoing definitive
      instrumented final fusion (FF) following implantation of a growing construct.
      Charts and radiographs were queried for all patients who underwent FF after
      management of EOSD with a distraction-based posterior construct at a single
      institution from 2006 to 2017. Patients managed during the growth modulation
      period with either proximal rib or spinal fixation were included. Thirteen
      patients qualified for inclusion. Spinal deformity etiologies were varied
      (neuromuscular: 5, idiopathic: 4, congenital: 4). Average age at implantation was
      6.5 years, and patients underwent an average of 8.15 lengthening procedures over
      an average of 69 months. After the growing program, modest correction in main
      coronal Cobb was obtained at FF (average 52.4 degrees  before FF, 37.6 degrees 
      following FF, P<0.001; average percent improvement of 27%). Five patients
      required posterior column osteotomies. Using criteria proposed by Flynn and
      colleagues, 'minimal' coronal correction was achieved in 23% of patients and
      'moderate' in 77%. No patient achieved 'substantial' (>50%) correction.
      Subjective poor bone quality was appreciated in 67% of patients, and 85% were
      noted to have areas of autofusion over previously spanned levels. Two (15%)
      patients sustained a total of four complications. After growth modulation
      procedures, EOSD deformities are generally stiff, bone quality is often
      subjectively poor, and autofusion is common, even after use of proximally rib
      based systems. Modestly improved coronal Cobb correction can be obtained at FF
      but may require single or multiple posterior osteotomies. Intraoperative
      difficulties can be expected, and clinicians should be alert for intraoperative
      and postoperative complications.

PMID- 30300259
TI  - XXXI. Julius Schottlaender.

PMID- 30300261
TI  - Foreword.

PMID- 30300262
TI  - Vitamin D: Immunomodulatory Aspects.
AB  - Vitamin D is a group of liposoluble prohormones consisting of 5 different
      vitamins, the most important forms being vitamin D2 and vitamin D3. The
      ergocalciferol (vitamin D2) is less efficacious and derives from irradiated
      fungi, while colecalciferol (vitamin D3), derived from cholesterol, is
      synthesized via ultraviolet B rays in animal organisms. Only the ultraviolet B
      rays (290 to 315 nm) portion of the solar ray photolyzes 7-dehydrocholesterol in
      the skin to previtamin D3, which is converted subsequently to vitamin D3.
      Moreover, the skin makes little vitamin D from the sun at latitudes above 37
      degrees north or below 37 degrees south of the equator. Calcidiol [25(OH)D] is
      the more stable metabolite of vitamin D in serum and the best indicator of the
      vitamin D status. Optimal values range are >30 ng/mL. Calcitriol [1,25(OH)2D] is
      the active hormone form of vitamin D. The 1,25(OH)2D binds to its nuclear
      receptor (vitamin D receptor), expressed in many tissues, regulating the
      expression of genes involved in calcium metabolism, cell differentiation,
      apoptosis, and immunity. About immunity, calcitriol stimulates innate immune
      responses by enhancing the chemotactic and phagocytotic responses of macrophages
      as well as the production of antimicrobial peptides. 1,25(OH)2D strongly enhances
      production of interleukine-10 by stimulating T regulatory cells and inhibiting
      Th1 and Th17 cell differentiation. Furthermore, several studies suggest that
      lower 25(OH)D serum levels are associated with an increased risk of respiratory
      infection at all ages in a dose-response manner.

PMID- 30300260
TI  - Treatment With Tumor-infiltrating Lymphocytes in Advanced Melanoma: Evaluation of
      Early Clinical Implementation of an Advanced Therapy Medicinal Product.
AB  - Tumor-infiltrating lymphocytes (TIL)-therapy in advanced melanoma is an advanced
      therapy medicinal product (ATMP) which, despite promising results, has not been
      implemented widely. In a European setting, TIL-therapy has been in use since 2011
      and is currently being evaluated in a randomized controlled trial. As clinical
      implementation of ATMPs is challenging, this study aims to evaluate early
      application of TIL-therapy, through the application of a constructive technology
      assessment (CTA). First the literature on ATMP barriers and facilitators in
      clinical translation was summarized. Subsequently, application of TIL-therapy was
      evaluated through semistructured interviews with 26 stakeholders according to 6
      CTA domains: clinical, economic, patient-related, organizational, technical, and
      future. In addition, treatment costs were estimated. A number of barriers to
      clinical translation were identified in the literature, including: inadequate
      financial support, lack of regulatory knowledge, risks in using live tissues, and
      the complex path to market approval. Innovative reimbursement procedures could
      particularly facilitate translation. The CTA survey of TIL-therapy acknowledged
      these barriers, and revealed the following facilitators: the expected
      effectiveness resulting in institutional support for an internal pilot, the
      results of which led to the inclusion of TIL-therapy in a national coverage with
      evidence development program, the availability of an in-house pharmacist, quality
      assurance expertise and a TIL-skilled technician. Institutional and national
      implementation of TIL-therapy remains complex. The promising clinical
      effectiveness is expected to facilitate the adoption of TIL-therapy, especially
      when validated through a randomized controlled trial. Innovative and conditional
      reimbursement procedures, together with the organization of knowledge transfer,
      could support and improve clinical translation of TIL and ATMPs.

PMID- 30300263
TI  - ULTRASOUND IN VITRECTOMY: An Alternative Approach to Traditional Vitrectomy
      Techniques.
AB  - PURPOSE: To study a prototype of an ultrasound-based vitrector, and to try to
      understand the physical phenomena underlying this new technology. METHODS: We
      tested the ultrasound-based vitrector prototype (UV) (ultrasonically-driven
      handpiece obtained from a modified version of the Alcon CONSTELLATION Vision
      System [Alcon]) using an automatic experimental setup. Balanced saline solution
      (BSS) and vitreous (from fresh postmortem enucleated porcine eyes) flow rates
      were analyzed using three different tips. RESULTS: In general, BSS solution flow
      rates increased with increasing aspiration levels and decreased when we used % US
      power. Vitreous flow rates were influenced by aspiration levels, % US power, and
      ultrasound-related phenomena: cavitation phenomenon and "jet streaming."
      CONCLUSION: Ultrasound-based vitrectomy may represent an important alternative to
      traditional vitrectomy. Such a tool, capable of liquefying and excising the
      vitreous body using ultrasound, could overcome all the limits of the guillotine
      based technique (GV). Knowledge of the physical phenomena underlying ultrasound
      based technology is a necessary prerequisite for further development of this new
      technology.

PMID- 30300264
TI  - MESOPIC AND DARK-ADAPTED TWO-COLOR FUNDUS-CONTROLLED PERIMETRY IN GEOGRAPHIC
      ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.
AB  - PURPOSE: To investigate retinal sensitivity in the junctional zone of geographic
      atrophy (GA) secondary to age-related macular degeneration using patient-tailored
      perimetry grids for mesopic and dark-adapted two-color fundus-controlled
      perimetry. METHODS: Twenty-five eyes with GA of 25 patients (prospective, natural
      history Directional Spread in Geographic Atrophy study [DSGA; NCT02051998]) and
      40 eyes of 40 normal subjects were included. Patient-tailored perimetry grids
      were generated using annotated fundus autofluorescence data. Customized software
      positioned test-points along iso-hulls surrounding the GA boundary at distances
      of 0.43 degrees , 0.86 degrees , 1.29 degrees , 2.15 degrees , and 3.01 degrees .
      The grids were used for duplicate mesopic and dark-adapted two-color (cyan and
      red) fundus-controlled perimetry. Age-adjusted reference-data were obtained
      through regression analysis of normative data followed by spatial interpolation.
      RESULTS: The mean sensitivity loss for mesopic testing decreased with the
      distance to GA (-10.3 dB [0.43 degrees ], -8.2 dB [0.86 degrees ], -7.1 dB [1.29
      degrees ], -6.8 dB [2.15 degrees ], and -6.6 dB [3.01 degrees ]; P < 0.01). Dark
      adapted cyan sensitivity loss exceeded dark-adapted red sensitivity loss for all
      iso-hulls (-14.8 vs. -11.7 dB, -13.5 vs. -10.1 dB, -12.8 vs. -9.1 dB, -11.6 vs. 
      8.2 dB, -10.7 vs. -8.0 dB; P < 0.01). CONCLUSION: Patient-tailored fundus
      controlled perimetry grids allowed for testing of retinal function in the
      junctional zone of GA with high spatial resolution. A distinct decrease in
      mesopic sensitivity loss between 0.43 degrees  (125 um) and 1.29 degrees  (375
      um) was observed that leveled off at more distant test-points. In proximity to
      the GA boundary, the results indicate that rod exceeded cone dysfunction.

PMID- 30300265
TI  - COMPARISON BETWEEN RELEASABLE SCLERAL BUCKLING AND VITRECTOMY IN PATIENTS WITH
      PHAKIC PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT.
AB  - PURPOSE: To compare the efficiency of releasable scleral buckling (RSB) and pars
      plana vitrectomy (PPV) in the treatment of phakic patients with primary
      rhegmatogenous retinal detachment. METHODS: The current study was a prospective
      randomized clinical trial. One hundred and ten eyes from 110 patients with
      primary rhegmatogenous retinal detachment and proliferative vitreoretinopathy of
      Grade B or less were included in this study. The patients were randomly allocated
      into an RSB group and a PPV group. The functional and anatomical success was
      compared between groups. RESULTS: The primary anatomical success rate (PPV 41/43
      [95.35%] and RSB 38/41 [92.68%]) and final anatomical success rate (PPV and RSB
      100%) showed a nonsignificant difference. The best-corrected visual acuity,
      intraocular pressure, and complications were not different between the groups.
      However, the incidence of cataract progression was higher in the PPV group (26 of
      43 [60.47%]) than in the RSB group (4 of 41 [9.76%]) at the 12-month follow-up.
      The subfoveal choroidal thickness increased significantly in the RSB group 3
      months after surgery, but no longer differed at the postoperative 6-month and 12
      month follow-ups. The axial length had increased significantly 1 month after
      surgery, but the difference was no longer significant at 3 months, 6 months, and
      12 months. CONCLUSION: The RSB and PPV procedures have the same effects on the
      functional and anatomical success for patients with phakic primary rhegmatogenous
      retinal detachment. Nevertheless, based on the few cases of intraocular
      complications and cataract progression, we believe that the RSB technique should
      be preferentially recommended.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- 30300266
TI  - RELATIONSHIP BETWEEN STAGES OF DIABETIC RETINOPATHY AND LEVELS OF BRAIN-DERIVED
      NEUROTROPHIC FACTOR IN AQUEOUS HUMOR AND SERUM.
AB  - PURPOSE: The aim of the study was to determine aqueous humor and serum levels of
      brain-derived neurotrophic factor (BDNF) in diabetic patients with and without
      retinopathy. METHODS: The study included diabetic patients with or without
      retinopathy, who had an indication for cataract surgery. The study groups were
      diabetic patients without retinopathy (Group 2), with nonproliferative diabetic
      retinopathy (Group 3), and with proliferative retinopathy (Group 4). To
      quantitatively determine the amount of BDNF in samples, the RayBio Human BDNF
      ELISA kit (Norcross, GA), based on an enzyme-labeled immunosorbent assay was
      used. RESULTS: The median serum BDNF levels were significantly lower in all the
      study groups than in the control group (P values: 0.038 Group 2, 0.02 Group 3,
      and 0.002 Group 4). Serum BDNF was lower in Group 4 than in Group 3 (P = 0.030),
      and in Group 3 than in Group 2 (P = 0.04). The median aqueous humor BDNF levels
      were significantly decreased in all groups (P values: 0.047 Group 2, 0.021 Group
      3, and 0.007 Group 4). There was no significant difference between Groups 2, 3,
      and 4 (P = 0.214). CONCLUSION: The serum and aqueous humor BDNF levels decreased
      in patients with diabetes mellitus (DM) before the emergence of clinical signs of
      retinopathy.

PMID- 30300267
TI  - CHANGES OF AQUEOUS HUMOR MULLER CELLS' BIOMARKERS IN HUMAN PATIENTS AFFECTED BY
      DIABETIC MACULAR EDEMA AFTER SUBTHRESHOLD MICROPULSE LASER TREATMENT.
AB  - PURPOSE: To evaluate the changes in activity of biomarkers of Mu[Combining
      Diaeresis]ller cells (MC) in aqueous humor of patients with diabetic macular
      edema after subthreshold micropulse laser, over 1 year. METHODS: Patients with
      untreated diabetic macular edema and central retinal thickness <= 400 MUm were
      enrolled. Best-corrected visual acuity, full ophthalmic examination, and optical
      coherence tomography were performed. Subthreshold micropulse laser was applied
      every 3 months. Glial fibrillary acidic protein and inwardly rectifying potassium
      channel (Kir 4.1), MC activity markers, and vascular endothelial growth factor
      were quantified in the aqueous humor collected at baseline and at 1, 3, and 12
      months after laser. Changes in the macular thickness and inner nuclear layer
      thickness, where MC bodies are located, were measured. RESULTS: Ten eyes of 10
      patients were included. Best-corrected visual acuity improved at 3 months (P =
      0.047) and remained stable. Inner nuclear layer thickness significantly reduced
      at 12 months (P = 0.012). Glial fibrillary acidic protein, Kir 4.1, and vascular
      endothelial growth factor decreased at 1 and/or 3 and/or 12 months compared with
      baseline (P < 0.05). CONCLUSION: Subthreshold micropulse laser improves visual
      function in diabetic macular edema. Kir 4.1 and glial fibrillary acidic protein
      decrease and inner nuclear layer thickness reduction demonstrate that
      subthreshold micropulse laser may restore MC function. Subthreshold micropulse
      laser also reduces vascular endothelial growth factor concentration. The effect
      of subthreshold micropulse laser in diabetic macular edema may in part be due to
      changes of MC metabolic activity.

PMID- 30300268
TI  - OUTCOME OF ACUTE NONTRAUMATIC VITREOUS HEMORRHAGE IN HEALTHY PATIENTS.
AB  - PURPOSE: To compare outcomes in dense vitreous hemorrhage versus mild vitreous
      hemorrhage due to nontraumatic posterior vitreous detachment. METHODS: We
      compared 315 eyes, divided into 2 patient groups, one with dense and the other
      with mild vitreous hemorrhage. The main outcome measures were final mean best
      corrected visual acuity, number of retinal tears, number of retinal detachments,
      and the number of pars plana vitrectomy and/or scleral buckle surgeries. RESULTS:
      In 33.4% of the patients, posterior vitreous detachment without complications was
      found. Retinal breaks after posterior vitreous detachment were found in 59% of
      the eyes. Rhegmatogenous retinal detachment was principally treated with pars
      plana vitrectomy and scleral buckle. In nonvisible fundus hemorrhage group, 44.4%
      of the patients underwent vitrectomy. In visible fundus hemorrhage group, 9.52%
      of the patients underwent pars plana vitrectomy. The mean final visual acuity was
      20/25, without significant difference between groups (P = 0.064). CONCLUSION:
      Acute, spontaneous, nontraumatic posterior vitreous separation with vitreous
      hemorrhage is associated with a high incidence of retinal complications. Close
      follow-up is necessary. We did not find significant differences in final visual
      acuity neither between the two groups nor among the treatments.

PMID- 30300269
TI  - GENETIC RISK FACTORS IN ACUTE CENTRAL SEROUS CHORIORETINOPATHY.
AB  - PURPOSE: To investigate genetic associations in white patients with acute central
      serous chorioretinopathy (aCSC) and to assess genetic differences between aCSC
      and chronic CSC (cCSC). METHODS: A total of 135 aCSC patients, 272 cCSC patients,
      and 1,385 control individuals were included. Eight single nucleotide
      polymorphisms were genotyped for ARMS2 (rs10490924), CFH (rs800292, rs1061170,
      rs1065489, rs1329428, rs2284664, rs3753394), and NR3C2 (rs2070951). Also, C4B
      gene copy numbers were analyzed. RESULTS: Three single nucleotide polymorphisms
      in the CFH gene were significantly associated with aCSC: rs800292 (P = 0.003,
      odds ratio = 1.53 [95% confidence interval = 1.15-2.03]), rs1061170 (P = 0.002,
      odds ratio = 0.64 [95% confidence interval = 0.48-0.86]), and rs1329428 (P = 5.87
      * 10, odds ratio = 1.83 [95% confidence interval = 1.40-2.38]). A significant
      difference was found in the distribution of C4B gene copy numbers in aCSC
      patients compared with controls (P = 0.0042). No differences could be found among
      the selected variants between aCSC and cCSC patients. CONCLUSION: Three variants
      in the CFH gene and copy number variations in C4B were found to be significantly
      associated with the risk of aCSC development. Despite the differences in clinical
      presentation, acute and chronic CSC may share a similar genetic predisposition
      based on our present analysis. Other genetic and/or nongenetic risk factors may
      be more influential in the differentiation toward an acute or a chronic phenotype
      of CSC.

PMID- 30300270
TI  - Correspondence.

PMID- 30300271
TI  - Reply.

PMID- 30300272
TI  - Reply.

PMID- 30300273
TI  - Combined Reconstruction of the Medial Patellofemoral Ligament (MPFL) and Medial
      Quadriceps Tendon-Femoral Ligament (MQTFL) for Patellar Instability in Children
      and Adolescents: Surgical Technique and Outcomes.
AB  - OBJECTIVES: A variety of surgical options exist to treat the challenging problem
      of recurrent patellar instability in children and adolescents. The goal of the
      current study is to describe a novel combined reconstruction technique of both
      the medial patellofemoral ligament (MPFL) and the medial quadriceps tendon
      femoral ligament (MQTFL) and report patient outcomes of a single-surgeon series.
      METHODS: All patients studied underwent simultaneous MPFL and MQTFL
      reconstruction for patellar instability using gracilis allograft. Demographic,
      clinical, and radiographic data were collected. Subjective outcomes were assessed
      for a minimum of 1 year postoperatively. RESULTS: Twenty-five patients (27
      knees), including 15 female and 10 male individuals with an average age of 15.0+/
      2.2 years (range, 10.3 to 18.9), were included. Prior ipsilateral patellofemoral
      surgery had been performed in 6 of 25 (24%) patients. Simultaneous
      hemiepiphysiodesis for valgus deformity at the time of combined reconstruction
      was performed in 5 of 25 (20%) patients. Preoperative imaging showed a mean
      tibial tubercle-trochlear groove of 17.2+/-3.8, Caton-Deschamps Index (CDI) of
      1.13+/-0.16, and trochlear dysplasia Dejour A/B [22/26 (85%)] or Dejour C/D [4/26
      (15%)]. A total of 18 patients (19 knees, 72%) returned outcomes questionnaires
      at a mean 2.0+/-0.5 years after surgery. Mean Kujala, Pedi-IKDC, and Lysholm
      scores were 85.9+/-13.9, 81.5+/-15.2, and 84.3+/-13.5, respectively. Later
      revision procedure (tibial tubercle osteotomy) for recurrent patellar instability
      was required in 2 of 25 patients (8%) patients, and another patient reported
      persistent instability not requiring revision. Return to sports was possible in
      10 of 13 self-reported athletes (77%) at a mean of 5.8+/-3.9 months (range, 2 to
      15). CONCLUSIONS: The present study describes a combined MPFL-MQTFL
      reconstruction technique with favorable short-term results. Although particularly
      useful in the skeletally immature patient where tibial tubercle osteotomy should
      be avoided and patellar fixation minimized, combined reconstruction may
      potentially be appropriate for older patients with patellofemoral instability as
      well. This technique more closely recreates the native anatomy of both the MPFL
      and MQTFL, may decrease the risk of patellar fracture, and can be useful in the
      revision setting. LEVEL OF EVIDENCE: Level IV.

PMID- 30300274
TI  - Persistence and Progression of Airway Obstruction in Children With Early Onset
      Scoliosis.
AB  - BACKGROUND: Obstructive lung disease occurs in 30% of children with early onset
      scoliosis (EOS); changes in degree of airway obstruction over time have not been
      reported. METHODS: Longitudinal patterns of incidental, persistent, and
      progressive airway obstruction were retrospectively analyzed in a cohort of
      children with EOS with at least 1 forced expiratory volume in 1 second
      (FEV1)/forced vital capacity (FVC) value <85% on serial spirometric assessments
      over a >=3-year observation period. The prevalence of clinical features and the
      severity of coronal and sagittal spine deformities for each group at the
      beginning and end of the study period were compared. RESULTS: Airway obstruction
      was incidental in 12 (24%) and persistent in 37 (76%) of 49 children with EOS.
      Twenty of 37 (54%) of those with persistent obstruction developed progressive
      airway obstruction. The decline in FEV1/FVC over 6+/-2 years was insignificant in
      the incidental group (4%+/-2%) and the persistent nonprogressive group (7%+/-4%)
      but significant in the progressive group (13%+/-4%, t test; P=0.002). In total,
      29% of the 49 children at the onset and 57% at the end of the study had airway
      obstruction. The incidental, persistent nonprogressive, and progressive groups
      did not differ with regard to age, diagnosis distribution, or sex. The initial
      coronal curve size, apex, direction of the curve, and degree of kyphosis were
      statistically similar among the 3 groups. Coronal curve magnitude inversely
      correlated with FEV1/FVC at the end but not the beginning of the study (r=-0.19,
      P=0.002). Six of 19 responded to bronchodilator treatment, suggesting concurrent
      asthma. Airway obstruction did not relate to restrictive pulmonary abnormalities
      measured by FVC at first or last timepoints [slope=-0.076 (95% confidence
      interval, -0.99 to 0.038; P=0.19)]. Changes in degrees of airway obstruction and
      restrictive lung disease over time did not correlate [slope=-0.125 (95%
      confidence interval, -0.294 to 0.044; P=0.14)]. CONCLUSIONS: Children with EOS
      and progressive airway obstruction represent an important subgroup which may
      require new surgical and nonsurgical treatment strategies to prevent loss of lung
      function over time.

PMID- 30300276
TI  - Hip Status and Long-term Functional Outcomes in Spina Bifida.
AB  - BACKGROUND: Nearly 50% of individuals with myelomeningocele will develop a
      dislocated hip by skeletal maturity. The purpose of this study was to determine
      the influence of hip status on functional outcomes in a cohort of adult patients
      with myelomeningocele. METHODS: Patients with a diagnosis of myelomeningocele >18
      years were prospectively enrolled over a 12-month period. Neurological level of
      involvement was obtained from chart review and interview. Clinical examination
      included hip range of motion and leg-length discrepancy. Reimer's migration index
      was calculated from a current anteroposterior pelvic radiograph. All subjects
      completed the VR-12 and the NIH PROMIS outcomes measures for pain interference
      and physical function. The chi, the Pearson correlation coefficients, and linear
      regression models were applied to evaluate the influence of hip status on
      functional outcomes. RESULTS: In total, 31 patients (average age 31, range 19 to
      49) were included. Eight thoracic, 9 lumbar, and 14 sacral level patients
      participated. Twenty had bilaterally located hips, 5 had a unilateral subluxation
      or dislocation, and 6 had bilaterally subluxated or dislocated hips. In
      univariate analysis, patients with bilaterally located hips performed better in
      lower extremity function than those with unilateral subluxation/dislocation (36.7
      vs. 26.0; P=0.03) but worse in pain interference than those with bilateral
      subluxation/dislocation (52.0 vs. 43.3; P=0.03). After controlling for
      neurological level, there was no statistically significant difference in the VR
      12 mental (P=0.32) or physical component summary (P=0.32) scores, nor in the
      PROMIS lower extremity function (P=0.26) or pain interference scores (P=0.33)
      between groups. Decreased extension and abduction were indirectly correlated with
      VR-12 mental component scores (P=0.0038, 0.0032). Leg-length discrepancy was not
      associated with any outcome measure. CONCLUSIONS: Long-term outcomes are not
      associated with hip status in adult patients with myelomeningocele. Functional
      outcomes are more closely correlated with neurological level and hip range of
      motion. These results suggest efforts to keep myelomeningocele hips reduced are
      likely without functional benefit and should be avoided in favor of maintaining
      motion with contracture release as needed. LEVEL OF EVIDENCE: Level III.

PMID- 30300275
TI  - C-Reactive Protein Predicts Risk of Venous Thromboembolism in Pediatric
      Musculoskeletal Infection.
AB  - BACKGROUND: The rate of venous thromboembolism in children with musculoskeletal
      infections (MSKIs) is markedly elevated compared with hospitalized children in
      general. Predictive biomarkers to identify high-risk patients are needed to
      prevent the significant morbidity and rare mortality associated with thrombotic
      complications. We hypothesize that overactivation of the acute phase response is
      associated with the development of pathologic thrombi and we aim to determine
      whether elevations in C-reactive protein (CRP) are associated with increased
      rates of thrombosis in pediatric patients with MSKI. METHODS: A retrospective
      cohort study measuring CRP in pediatric MSKI patients with or without thrombotic
      complications. RESULTS: The magnitude and duration of elevation in CRP values
      correlated with the severity of infection and the development of pathologic
      thrombosis. In multivariable logistic regression, every 20 mg/L increase in peak
      CRP was associated with a 29% increased risk of thrombosis (P<0.001). Peak and
      total CRP were strong predictors of thrombosis with area under the receiver
      operator curves of 0.90 and 0.92, respectively. CONCLUSIONS: Future prospective
      studies are warranted to further define the discriminatory power of CRP in
      predicting infection-provoked thrombosis. Pharmacologic prophylaxis and increased
      surveillance should be strongly considered in patients with MSKI, particularly
      those with disseminated disease and marked elevation of CRP. LEVEL OF EVIDENCE:
      Level III.

PMID- 30300277
TI  - Utilization of a Wide Array of Nonvalidated Outcome Scales in Pediatric
      Orthopaedic Publications: Can't We All Measure the Same Thing?
AB  - PURPOSE: Clinical changes are best evaluated with standardized, validated
      outcomes, including both patient-reported outcome measures and surgeon-reported
      outcome measures (PROMs and SROMs). The purpose of this study was to describe the
      spectrum of outcome measures used in pediatric orthopaedic publications over the
      past 10 years and to determine the proportion that are in fact age-appropriate,
      validated, and appropriately applied in terms of condition and population.
      METHODS: The Journal of Bone and Joint Surgery, The Bone and Joint Journal,
      Journal of Pediatric Orthopaedics A and B, and Journal of Children's Orthopaedics
      were systematically searched for studies including children aged 18 and below,
      over a 10-year period from January 2005 to December 2014. Economic evaluations,
      letters, editorials, review articles, and clinical guidelines were excluded.
      SROMs and PROMs used were extracted, as were details on subject age and condition
      for which they were used. Each outcome scale was assessed for validity, and the
      proportion of scales used appropriately was calculated. Cochrane-Armitage test of
      trend was used to determine changes in PROM and SROM utilization over the study
      period. RESULTS: A total of 4614 articles were identified, of which 2251 met
      inclusion and exclusion criteria. In total, 259 (11.5%) of studies used a PROM,
      whereas 326 (14.5%) used a SROM. A total of 230 different outcome scales were
      identified; 115 were patient reported and 115 were surgeon reported. However,
      only 18.7% of SROMs and 38.3% of PROMs were applied to an age and disease
      appropriate demographic. Overall, there was a significant increase in the overall
      utilization of PROMs during the study period (P=0.004), but no corresponding
      increase in pediatric-validated PROMs (P=0.164). SROM utilization did not
      significantly change over the study period (P=0.337). CONCLUSIONS: Within the
      field of pediatric orthopaedics, an expansive variety of outcome scales are used,
      many of which have not been validated in children. Improved uniformity in
      reporting of outcomes and use of disease and age-validated outcomes scales is
      essential to improve multicenter research collaboration and data quality to
      generate appropriate evidence-based conclusions and treatment strategies in
      pediatric orthopaedics. LEVEL OF EVIDENCE: Level IV-systematic review.

PMID- 30300278
TI  - Comparison of 3 Pediatric Pelvic Osteotomies for Acetabular Dysplasia Using
      Patient-specific 3D-printed Models.
AB  - BACKGROUND: Children with developmental dysplasia of the hip may require a pelvic
      osteotomy to treat acetabular dysplasia. Three osteotomies are commonly performed
      in these patients (Pemberton, Dega, and San Diego), though comparative studies of
      each are limited. The purpose of this study was to compare changes in acetabular
      morphology (acetabular version, volume, and octant coverage angles) created by
      these 3 osteotomies using matched patient-specific 3D-printed pelvic models.
      METHODS: Fourteen patients with developmental dysplasia of the hip and
      preoperative computed tomography (CT) imaging were retrospectively included. For
      each patient CT, bone and cartilage tissues were independently segmented, and 3
      identical pelvises were 3D-printed using a dual material printer. Bone was
      printed with rigid material and cartilage with flexible material to simulate the
      flexibility of the triradiate cartilage and pubic symphysis. Pemberton, Dega, and
      San Diego acetabular osteotomies were performed on the triplicate set of 3D
      prints. Acetabular version, volume, and octant coverage angles (posterior,
      superior-posterior, superior, superior-anterior, and anterior) were determined
      before and after each mock surgery by morphologic assessment using preoperative
      and postoperative CT images. RESULTS: San Diego osteotomy yielded a small
      increase (+3.34+/-1.71 degrees) in version, compared with decreases with
      Pemberton (-5.47+/-1.54 degrees) and Dega (-8.57+/-1.21 degrees, P<0.05).
      Acetabular volume decreased similarly for Pemberton (-13.36%+/-2.88%), Dega (
      19.21%+/-2.73%), and San Diego (-19.29%+/-2.44%; P=0.215) osteotomies. San Diego
      osteotomy tended to have a larger postoperative increase in the posterior
      regions, and the Dega and Pemberton osteotomies tended to have larger
      postoperative increases in the anterior coverage regions. CONCLUSIONS:
      Quantifiable differences were identified in acetabular octant coverage angles and
      version between the 3 pelvic osteotomies. San Diego osteotomy increased
      acetabular coverage posteriorly resulting in acetabular anteversion, whereas
      Pemberton and Dega had greater superior-anterior coverage resulting in relative
      acetabular retroversion. This study is the first known to utilize 3D-printed
      models for comparison of surgical approaches in pediatric pelvic osteotomies.

PMID- 30300279
TI  - Biomechanical Assessment of Torsional Stiffness in a Supracondylar Humerus
      Fracture Model.
AB  - BACKGROUND: We assessed the effect on the torsional stability by different pin
      diameters and varied pin configurations in a biomechanical supracondylar humerus
      fracture model. METHODS: After scanning a model of a pediatric humerus, the image
      was imported into software. Variable pin trajectories were planned. Acrylonitrile
      butadiene styrene plastic models were 3-dimensionally printed with predetermined
      pin trajectories. Models were osteotomized and potted with a polyurethane resin.
      Five-pin configurations were designed to test coronal and sagittal patterns of
      pin placement. Each included 3 lateral pins and a medial pin. Pin diameters of
      1.6, 2.0, and 2.4 mm were tested in all configurations. Three models for each pin
      diameter/configuration were tested to ensure uniformity. Stability of the
      construct was tested to determine the torque needed to deflect the osteotomy 10
      degrees in internal/external rotation. Each model was tested 3 times. RESULTS: In
      all models/configurations, the 2.4 mm pin diameter was statistically stiffer than
      1.6 mm diameter pins; this lost statistical significance in certain patterns when
      comparing 2.0- and 2.4-mm pins. When comparing a divergent to a parallel
      configuration in the coronal plane, there was no significant difference in
      stability when pin diameter or number were controlled. The convergent pin
      configuration was, in general, the least stable pattern. Use of a medial pin
      conferred statistically significant stiffness throughout most models as
      demonstrated with pin deletion. Use of 2 pins was significantly less stiff than
      most 3-pin models. CONCLUSIONS: Larger pin diameters confer greater stiffness
      among all patterns. The use of 3 lateral and 1 medial pin was not statistically
      different than 2 lateral and 1 medial pin in our models. Both patterns were
      stiffer than 3 lateral pins only or other fewer pin constructs. The alignment of
      pins in the sagittal plane did not affect overall construct stiffness.

PMID- 30300280
TI  - Emerging Ethical Challenges Raised by the Evolution of Vascularized Composite
      Allotransplantation.
AB  - BACKGROUND: Despite early skepticism, the field of vascularized composite
      allotransplantation (VCA) has demonstrated feasibility. The ethics of VCA have
      moved past doubts about the morality of attempting such transplant to how to
      conduct them ethically. METHODS: Leaders of each program performing and/or
      evaluating VCA in the United States were invited to participate in a working
      group to assess the state and future of VCA ethics and policy. Four meetings were
      held over the course of 1 year to describe key challenges and potential
      solutions. RESULTS: Working group participants concluded that VCA holds great
      promise as treatment for patients with particular injuries or deficits, but the
      field faces unique challenges to adoption as standard of care, which can only be
      overcome by data sharing and standardization of evaluation and outcome metrics.
      CONCLUSIONS: Adequate attention must be given to concerns including managing the
      uniquely intense physician-patient relationship, ethical patient selection,
      ensuring patients have adequate representation, informing and earning the trust
      of the public for donation, standardizing metrics for success, and fostering an
      environment of data sharing. These steps are critical to transitioning VCA from
      research to standard of care, and to its insurance coverage inclusion.

PMID- 30300281
TI  - EVERYDAY PEOPLE SING A SIMPLE SONG: Establishing a core outcome for Life
      Participation.

PMID- 30300282
TI  - Urinary TIMP-2 predicts the presence and duration of delayed graft function in
      donation after circulatory death kidney transplant recipients.
AB  - BACKGROUND: Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin
      like growth factor binding protein-7 (IGFBP7) have been validated as biomarkers
      for acute kidney injury. We investigated the performance of both markers in
      predicting the occurrence and duration of functionally defined delayed graft
      function (fDGF) in donation after circulatory death (DCD) kidney transplant
      recipients. METHODS: Urine samples of 74 DCD recipients were analyzed. TIMP-2 and
      IGFBP7 were measured with ELISA on postoperative day 1 to 7, day 10, week 6 and
      month 6 and values were corrected for osmolality (mOsm). Immunosuppression
      consisted of anti-CD25 antibody induction and triple maintenance therapy
      (steroids, MMF and CNI). Statistical analysis included receiver operating
      characteristic curves and multivariate logistic regression. RESULTS: Fifty-one
      renal transplant recipients had fDGF (69%), of which 14 experienced prolonged
      fDGF (>=21 days). TIMP-2/mOsm on day-1 and day-10 adequately identified patients
      with fDGF (AUC 0.91) and prolonged fDGF (AUC 0.80), respectively, whereas
      IGFBP7/mOsm did not (AUC 0.63 and 0.60). Multivariate analysis on day-1
      identified 24-hour urinary creatinine excretion and TIMP-2/mOsm as significant
      predictors of fDGF (AUC 0.90, 95% CI 0.80-0.98). The best predictors of prolonged
      fDGF on day-10 were 24-hour urinary creatinine excretion, TIMP-2/mOsm and total
      warm ischemia time with an AUC of 0.85 (95% CI: 0.72-0.95). Consecutive TIMP
      2/mOsm values showed a decrease in TIMP-2/mOsm prior to an increase in eGFR,
      enabling us to monitor fDGF and predict resolution of fDGF. CONCLUSION: Urinary
      TIMP-2, but not IGFBP7, is a promising biomarker to predict the occurrence and
      duration of fDGF in DCD kidney transplant recipients.

PMID- 30300283
TI  - Importance of Hematopoietic Mixed Chimerism for Induction of Renal Allograft
      Tolerance in Nonhuman Primates.
AB  - BACKGROUND: Although induction of durable mixed chimerism is required for murine
      skin allograft tolerance, renal allograft tolerance has been achieved after
      induction of only transient mixed chimerism in nonhuman primates (NHPs) and
      humans. To better define the level/duration of chimerism required for stable
      renal allograft tolerance, we retrospectively analyzed these parameters and
      compared them with transplant outcomes in NHP combined kidney and bone marrow
      transplant (CKBMT) recipients. METHODS: Peripheral blood levels and duration of
      myeloid or lymphoid chimerism were retrospectively analyzed in 34 NHP CKBMT
      recipients which were divided into 3 groups: Tolerance (TOL), n=10; chronic
      antibody-mediated rejection (CAMR), n=12; and T cell-mediated rejection (TCMR),
      n=12. RESULTS: All 4 of the recipients that failed to develop any chimerism lost
      their allografts due to TCMR after discontinuation of immunosuppression (56 +/- 3
      days). Among 30 recipients who successfully developed multilineage chimerism, 10
      achieved immunosuppression-free survival (1258 +/- 388 days), 12 eventually
      developed CAMR (932 +/- 155 days), and 8 developed TCMR (82 +/- 10 days). The
      maximum level but not duration of lymphoid chimerism was significantly higher in
      TOL recipients compared with both CAMR (p=0.0159) and TCMR (p=0.0074).
      Conversely, the maximum myeloid chimerism was significantly higher in TOL than in
      TCMR (p=0.0469), but not in CAMR. ROC analyses revealed that lymphoid chimerism
      levels of 3.1% or greater could reliably predict long-term immunosuppression-free
      renal allograft survival (p<0.0001). CONCLUSIONS: This retrospective study
      confirmed that induction of chimerism is essential for long-term
      immunosuppression-free survival, which best correlates with lymphoid chimerism
      levels higher than 3.1%.

PMID- 30300284
TI  - Establishing a Core Outcome Measure for Life Participation: a Standardized
      Outcomes in Nephrology - Kidney Transplantation (SONG-Tx) Consensus Workshop
      Report.
AB  - BACKGROUND: Kidney transplantation confers substantial survival and quality of
      life benefits for many patients with end-stage kidney disease compared with
      dialysis, but complications and side-effects of immunosuppression can impair
      participation in daily life activities. Life participation is a critically
      important patient-reported outcome for kidney transplant recipients but is
      infrequently and inconsistently measured in trials. We convened a consensus
      workshop on establishing an outcome measure for life participation for use in all
      trials in kidney transplantation. METHODS: Twenty-five (43%) kidney transplant
      recipients/caregivers and 33 (57%) health professionals from 8 countries
      participated in 6 facilitated breakout group discussions. Transcripts were
      analyzed thematically. RESULTS: Four themes were identified. Returning to
      normality conveyed the patients' goals to fulfill their roles (ie, in their
      family, work, and community) and reestablish a normal lifestyle after transplant.
      Recognizing the diverse meaning and activities of 'life' explicitly acknowledged
      life participation as a subjective concept that could refer to different
      activities (eg, employment, recreation, family duties) for each individual
      patient. Capturing vulnerability and fluctuations posttransplant (eg, due to
      complications and side-effects) distinguished between experiences in the first
      year posttransplant and the long-term impact of transplantation. Having a
      scientifically rigorous, feasible and meaningful measure was expected to enable
      consistent and frequent assessment of life participation in trials in kidney
      transplantation. CONCLUSIONS: A feasible and validated core outcome measure for
      life participation is needed so that this critically important patient-reported
      outcome can be consistently and meaningfully assessed in trials in kidney
      transplantation to inform decision-making and care of recipients.

PMID- 30300285
TI  - Temporal Trends Associated with the Rise in Alcoholic Liver Disease Related Liver
      Transplantation in the United States.
AB  - BACKGROUND: In the United States, alcoholic liver disease (ALD) has recently
      become the leading indication for liver transplantation (LT). METHODS: Using the
      United Network for Organ Sharing registry, we examined temporal trends in adult
      liver transplant waitlist registrants and recipients with chronic liver disease
      (CLD) due to ALD from 2007 to 2016. RESULTS: From 2007 to 2016, ALD accounted for
      20.4% (18 399) of all CLD waitlist (WL) additions. The age-standardized ALD WL
      addition rate was 0.459 per 100 000 US population in 2007; nearly doubled to
      0.872 per 100 000 US population in 2016 and increased with an average annual
      percent change of 47.56% (95% CI: 30.33% to 64.72%).The ALD WL addition rate
      increased over twofold among young (18-39 years) and middle-aged (40-59 years)
      adults during the study period. Young adult ALD WL additions presented with a
      higher severity of liver disease including Model for End-Stage Liver Disease
      score compared to middle aged and older adults (> 60 years). The number of annual
      ALD WL deaths readily rose from 2014 to 2016, despite an overall annual decline
      in all CLD WL deaths. Severe hepatic encephalopathy, low BMI (< 18.5) and
      diabetes mellitus were significant predictors for 1-year waitlist mortality.
      CONCLUSION: ALD-related WL registrations and LT have increased over the past
      decade with a disproportionate increase in young and middle-aged adults. These
      subpopulations within the ALD cohort need to be evaluated in future studies to
      improve our understanding of factors associated with these alarming trends.

PMID- 30300286
TI  - THE OUTCOME OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR INHERITED
      DISEASES IS INFLUENCED BY HLA MATCH, YEAR OF TRANSPLANTATION AND IMMUNIZED FEMALE
      DONOR.
AB  - BACKGROUND: For many inborn errors of metabolism (IEM), allogeneic hematopoietic
      stem cell transplantation (HUSCT) is the only cure. METHODS: We report the
      outcome in 160 patients with inherited diseases, who were treated with HSCT in 3
      decades. Median age was 3 years (range 0.1-63). Grafts were from matched related
      donors (MRDs, 56), matched unrelated donors (MUDs, 66), or HLA-mismatched donors
      (38). RESULTS: Graft failure (GF) occurred in 26 patients (16%), severe acute
      graft-versus-host disease (GVHD) in 9 (6%), and chronic GVHD in 23 (12%). Ten
      year survival was 64% before the year 2000 and 86% after that (p=0.01). Ten-year
      survival for MRD grafts was 90%, as opposed to 79% for MUD grafts and 56% for HLA
      mismatched grafts (p=0.03). In multivariate analysis, GF was associated with
      having an HLA-mismatched donor (p<0.05) or MUD (p=0.015) and with reduced
      intensity conditioning (p<0.01). Death was associated with year of transplant
      (p=0.015), having an HLA-mismatched donor (p<0.001), and being a male recipient
      from an immune female donor (p=0.05). CONCLUSIONS: The outcome after HSCT for IEM
      depends on HLA match, year and immune female donor.

PMID- 30300287
TI  - Nonalcoholic fatty liver disease: basic pathogenetic mechanisms in the
      progression from NAFLD to NASH.
AB  - Nonalcoholic fatty liver disease (NAFLD) represents a growing cause of chronic
      liver injury, especially in Western Countries, where it is becoming the most
      frequent indication for liver transplantation (OLTx). NAFLD encompasses a
      spectrum of diseases that from simple steatosis (pure NAFLD) can progress to
      Nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma
      (HCC). The pathogenesis of NAFLD and the mechanisms behind its progression to
      NASH have been extensively studied. However, while the processes that determine
      fat accumulation are mostly clear, the mechanisms associated with the progression
      of the disease are not fully characterized. In predisposed patients, lipid
      accumulation can promote lipotoxicity and mitochondrial dysfunction, thus
      triggering hepatocyte death, inflammation and fibrosis. The specific role of
      different lipids has been identified and free fatty acids as well as free
      cholesterol have been identified as toxic species. To make the picture more
      complex, the pathogenesis of NAFLD involves pathological connections between
      several organs, including the adipose tissue and the gut, with the liver. The
      "inflamed" adipose tissue plays a key role in the release of toxic lipids, while
      alterations in the gut-liver axis have been associated with the progression from
      NAFLD to NASH mediated by dysbiosis, alteration of intestinal barrier, and
      finally bacterial translocation, that can trigger proinflammatory and
      profibrogenetic pathways, finally leading to cirrhosis development.

PMID- 30300288
TI  - The Transplant Index (TI): A Novel Method To Predict Adult Liver Transplant
      Waitlist Outcomes.
AB  - BACKGROUND: The field of transplantation is shifting outcome priorities from 1
      year survival to more comprehensive metrics including transplant rate and
      waitlist mortality. Identifying disenfranchised candidates (high waitlist death
      risk, low transplantation chance) can be a focus to improve outcomes. METHODS:
      Given waitlist outcomes, (continued waiting, death, and transplantation), we
      aimed to identify factors predicting the likelihood candidates would undergo
      transplant or death by performing multivariate competing risk analyses of 121 198
      candidates in the United Network for Organ Sharing database. We incorporated
      these probabilities (likelihood of transplantation and waitlist death) into the
      transplant index (TI) to identify disenfranchised candidates (high likelihood of
      death, low likelihood of transplantation). RESULTS: Half of the patients had low
      incidences of death and transplantation within 90 days (TI-inactive). The
      remaining were stratified into 10 groups within a predictive index, the TI. Low
      TI groups (TI-10, 20, 30) had 90-day transplant rates of 50.8%, 41.6%, and 39.8%
      respectively, and their respective 90-day death rates were 22.8%, 15.1%, and
      10.9%. High-TI groups (TI 80, 90, >90) had 90-day transplantation rates of 53.7%,
      64.3%, and 73.9% respectively, and 90-day death rates of 5.9%, 6.5%, and 6.7%
      respectively. As TI increased, the likelihood of transplantation increased and
      that of death decreased. Low-TI groups represent the disenfranchised candidates.
      CONCLUSIONS: The TI identifies disenfranchised candidates on the adult liver
      transplant waitlist. This is the subgroup that would benefit the most from
      efforts to increase access to transplantation.

PMID- 30300289
TI  - Recommendations for management and treatment of nonalcoholic steatohepatitis.
AB  - The prevalence of nonalcoholic liver disease (NAFLD) is increasing worldwide in
      conjunction with the epidemic increase in obesity and metabolic risk factors.
      Consequently, NAFLD has become a leading indication for liver transplantation.
      While genetic factors play an important role in the pathogenesis of NAFLD,
      detrimental lifestyle trends favoring a calorically unrestricted diet rich in
      carbohydrates and unsaturated fat, prolonged sedentary periods or limited
      physical activity have major metabolic implications. In aggregate these
      physiological dysregulations constitute the main risk factors for the metabolic
      syndrome and NAFLD. The cornerstone of the treatment of NAFLD, is lifestyle
      changes, including modifications to diet and physical activity, to reduce body
      weight and liver fat, however adherence is notoriously poor and the epidemic of
      NAFLD continues to grow unimpeded. In the face of this unmet clinical need, the
      pharmacologic therapy of NAFLD has been expanding as the varied mechanistic
      pathways of NAFLD are elucidated. Beyond these approaches to treating NAFLD, the
      prevention of other liver diseases is additionally important. Chief among these
      is alcoholic liver disease, and heavy use is detrimental irrespective of
      underlying NAFLD. However, the impact of mild to moderate alcohol use in patients
      with mild or nonadvanced forms NAFLD is undefined. This article summarizes the
      results of the International Liver Transplant Society consensus meeting on NAFLD
      in liver transplantation. It describes the available evidence and provides
      consensus guidance on the lifestyle and pharmacologic therapies of NAFLD, and the
      consensus position on alcohol use in patients with NAFLD.

PMID- 30300290
TI  - Risperidone But Not Quetiapine Treatment Is Associated With Increased Appetite
      But Not Satiety Hormones in Children During An Oral Glucose Tolerance Test: A
      Pilot Study.
AB  - BACKGROUND: Second-generation antipsychotics (SGAs) are commonly used to treat
      children with mental health conditions (MHCs) but are associated with adverse
      effects including obesity, hypertension, dyslipidemia, and type 2 diabetes. The
      mechanisms underlying these complications are unknown, but it has been suggested
      that SGAs increase appetite leading to weight gain. The present objective was to
      perform a pilot study to investigate appetite and satiety hormones in SGA-treated
      (risperidone or quetiapine) and SGA-naive children with similar mental health
      conditions. METHODS: Oral glucose tolerance tests (OGTTs) were conducted in SGA
      naive (n = 18), risperidone-treated (n = 20), and quetiapine-treated (n = 16)
      children recruited from the British Columbia Children's Hospital Psychiatry
      Department. Over 5 time-points during the OGTT, appetite questionnaires using a
      visual analogue scale were administered, and blood was collected to measure
      ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, glucagon-like
      protein 1, leptin, and adiponectin. Mixed model analyses were conducted to
      examine between-group differences. RESULTS: The children were similar in age,
      psychiatric diagnosis, and global assessment of functioning scores. Body mass
      index z-scores were also similar between groups. Appetite was increased during
      the OGTT in the risperidone-treated compared with the SGA-naive group for 2
      questions ("How strong is your desire to eat"; P = 0.003 and "How much food do
      you think you can eat"; P = 0.028). No differences in satiety hormones were
      observed between the 3 groups. CONCLUSIONS: Risperidone treatment in youth is
      associated with elevated appetite during an OGTT, with no differences in gut
      peptides or adipocytokines to explain risperidone's effect on appetite. Further
      research is needed to explore other mediators of weight gain and metabolic
      dysfunction in SGA-treated youth.

PMID- 30300291
TI  - Clinical Characteristics of Patients With Schizophrenia Who Successfully
      Discontinued Antipsychotics: A Literature Review.
AB  - PURPOSE/BACKGROUND: Although discontinuing antipsychotics clearly increases the
      risk of relapse in schizophrenia, some patients remain clinically well without
      continuous antipsychotic treatment. However, data on the characteristics of such
      patients are still scarce. METHODS/PROCEDURES: A systematic literature review was
      conducted to identify predictive factors for successful antipsychotic
      discontinuation in schizophrenia using PubMed (last search; June 2018) with the
      following search terms: (antipsychotic* or neuroleptic) AND (withdraw* or cessat*
      or terminat* or discontinu*) AND (schizophreni* or psychosis). The search was
      filtered with humans and English. Factors associated with a lower risk of
      relapse, when replicated in 2 or more studies with a follow-up period of 3 months
      or longer, were considered successful. FINDINGS/RESULTS: Systematic literature
      search identified 37 relevant articles. Mean relapse rate after antipsychotic
      discontinuation was 38.3% (95% confidence interval = 16.0%-60.6%) per year.
      Factors associated with a lower risk of relapse were being maintained on a lower
      antipsychotic dose before discontinuation, older age, shorter duration of
      untreated psychosis, older age at the onset of illness, a lower severity of
      positive symptoms at baseline, better social functioning, and a lower number of
      previous relapses. IMPLICATIONS/CONCLUSIONS: Although this literature review
      suggests some predictors for successful antipsychotic withdrawal in patients with
      schizophrenia, the very limited evidence base and unequivocally high relapse
      rates after discontinuation must remain a matter of serious debate for
      risk/benefit considerations.

PMID- 30300292
TI  - Hallucinogen Persisting Perception Disorder After Ibogaine Treatment for Opioid
      Dependence.

PMID- 30300294
TI  - In Memoriam: Bernard J. Carroll, MD, PhD.

PMID- 30300293
TI  - Very Low-Dose Mirtazapine (7.5 mg) in Treatment of Acute Antipsychotic-Associated
      Akathisia.
AB  - BACKGROUND: Some evidence suggests that off-label use of mirtazapine (15 mg) is
      effective in treatment of acute antipsychotic-associated akathisia (AAA). We
      analyzed whether a lower dose of mirtazapine (7.5 mg) maintained its
      antiakathisia properties while exhibiting better tolerability in patients with
      schizophrenia and mood disorders who developed acute AAA. METHODS: Medical charts
      were retrospectively evaluated for 12 patients with AAA. All scored at least 2
      (mild akathisia) on the Barnes Akathisia Rating Scale (BARS) and were treated
      with mirtazapine (7.5 mg) for a mean of 10.3 days. RESULTS: There was a
      statistically significant decrease in the BARS subjective, distress, and global
      (P < 0.01 to P < 0.001), but not objective (P = 0.63), subscales. Five
      participants (41.6%) fulfilled the predefined criterion of response, a decrease
      of at least 2 points on the BARS global subscale. The positive antiakathisia
      effect of mirtazapine was observed predominantly in aripiprazole-treated
      patients. Mirtazapine (7.5 mg) was well tolerated, and no clinically significant
      adverse effects, primarily drowsiness or increased appetite, were reported.
      CONCLUSIONS: A large-scale controlled evaluation is warranted to substantiate
      clinical utility of off-label use of mirtazapine (7.5 mg) for patients with AAA.

PMID- 30300296
TI  - Statistics Commentary Series: Commentary No. 29: Network Meta-Analysis.

PMID- 30300295
TI  - Age Impacts Olanzapine Exposure Differently During Use of Oral Versus Long-Acting
      Injectable Formulations: An Observational Study Including 8,288 Patients.
AB  - PURPOSE: Olanzapine is a commonly prescribed antipsychotic available as oral and
      long-acting injectable (LAI) formulations. Data are lacking on the use and safety
      of olanzapine-LAI in older patients. The aim of this study was to investigate the
      effect of increasing age on olanzapine exposure during oral versus LAI
      administration in a real-life setting. METHODS: This observational study was
      based on routine therapeutic drug monitoring data collected during 2005-2017. As
      a measure of exposure, absolute concentrations and concentration/dose ratios of
      olanzapine were defined as outcome variables. Linear mixed-model analyzes were
      used to allow for inclusion of multiple samples per patient and adjustment for
      covariate effects. RESULTS: Olanzapine concentrations and doses from 8,288
      patients (21,378 measurements) were included. The number of patients on oral
      treatment was 7,893 (42%, 50 years or older), while 395 were using olanzapine-LAI
      (27%, 50 years or older). In contrast to oral use, where the dose-adjusted
      concentration of olanzapine increased significantly for patients 50 years or
      older (P < 0.001), increasing age had no effect on olanzapine concentration
      following LAI administration (P = 0.550). The effects of smoking habits and
      gender were equal in oral and olanzapine-LAI users. CONCLUSION: While the dose
      adjusted systemic exposure of olanzapine increases by age after oral
      administration, these novel findings from a large patient population show that
      systemic exposure of olanzapine-LAI is unaffected by age, probably due to the
      lacking influence of age-related changes in gastrointestinal absorption and/or
      presystemic metabolism. From a pharmacokinetic point of view, it is therefore no
      reason to restrict the use of olanzapine-LAI in older patients requiring long
      term treatment.

PMID- 30300297
TI  - The mysteries of menopause and urogynecologic health: clinical and scientific
      gaps.
AB  - OBJECTIVES: A significant body of knowledge implicates menopausal estrogen levels
      in the pathogenesis of the common pelvic floor disorders (PFDs). These health
      conditions substantially decrease quality of life, increase depression, social
      isolation, caregiver burden, and economic costs to the individuals and society.
      METHODS: This review summarizes the epidemiology of the individual PFDs with
      particular attention to the understanding of the relationship between each PFD
      and menopausal estrogen levels, and the gaps in science and clinical care that
      affect menopausal women. In addition, we review the epidemiology of recurrent
      urinary tract infection (rUTI)-a condition experienced frequently and
      disproportionately by menopausal women and hypothesized to be potentiated by
      menopausal estrogen levels. RESULTS: The abundance of estrogen receptors in the
      urogenital tract explains why the natural reduction of endogenous estrogen, the
      hallmark of menopause, can cause or potentiate PFDs and rUTIs. A substantial body
      of epidemiological literature suggests an association between menopause, and PFDs
      and rUTIs; however, the ability to separate this association from age and other
      comorbid conditions makes it difficult to draw definitive conclusions on the role
      of menopause alone in the development and/or progression of PFDs. Similarly, the
      causative link between the decline in endogenous estrogen levels and the
      pathogenesis of PFDs and rUTIs has not been well-established. CONCLUSIONS:
      Innovative human studies, focused on the independent effects of menopausal
      estrogen levels, uncoupled from tissue and cellular senescence, are needed.

PMID- 30300298
TI  - Clinical application and mid-term results of modified vaginal closure: pelvic
      symptoms, quality of life, satisfaction, and regret rate.
AB  - OBJECTIVE: To evaluate the safety and efficacy of a modified vaginal closure in
      older women with severe pelvic organ prolapse (POP) with respect to symptoms,
      quality of life, postoperative satisfaction, regret rate, and complications
      METHODS:: From March, 2014 to December, 2016, in all, 32 women were enrolled in
      the study. All the participants underwent a modified vaginal closure. Records
      were reviewed to collect demographic characteristics and perioperative
      parameters. The Pelvic Floor Distress Inventory-short form 20 (PFDI-20) and the
      Short Form 36 Health Survey Profile (SF-36) were used to evaluate pelvic symptoms
      and self-perceived quality of life, respectively, 6 months postoperatively and at
      the latest follow-up. The Patient Global Impression of Change (PGI-C) was used to
      estimate the satisfaction. The satisfaction and regret rates were assessed at the
      latest follow-up. RESULTS: After an average follow-up period of 23 months (range
      8-41 months), none of the 32 women experienced recurrence of prolapse that
      required reoperation. During follow-up, significant improvements were observed in
      the Pelvic Organ Prolapse Distress Inventory (POPDI-6), Urinary Distress
      Inventory (UDI-6), and SF-36 results (P < 0.001). However, the Colorectal-Anal
      Distress Inventory (CRADI-8) results did not improve significantly (P = 0.074).
      None of the participants regretted undergoing this procedure, and the PGI-C
      indicated a satisfaction rate of 93.8%. CONCLUSIONS: The modified vaginal closure
      showed a positive impact on POP and urinary symptoms, and consequently improved
      quality of life of the 32 participants. This procedure achieved a relatively high
      satisfaction rate and a low regret rate.

PMID- 30300299
TI  - High and dry: recognizing the impact of genitourinary syndrome of menopause.

PMID- 30300300
TI  - Tissue-selective estrogen complex for women who experience breast discomfort or
      vaginal bleeding when on hormone therapy.
AB  - OBJECTIVE: The objective of this study was to evaluate the effects of switching
      from hormone therapy to tissue-selective estrogen complex (TSEC) in women who
      experience vaginal bleeding or breast discomfort. METHODS: This retrospective
      cohort study included 82 postmenopausal women who received TSEC after switching
      from another hormone therapy due to adverse events. Changes in symptoms and
      imaging after switching to TSEC were evaluated. RESULTS: The mean age was 56.9
      years. The women were switched to TSEC due to vaginal bleeding in 56.1% and
      breast discomfort in 47.6% (multiple choices were allowed). After the switch,
      almost all women (97.6%) experienced an improvement in adverse events. However,
      27% of the women had worsening of vasomotor symptoms, which was more common when
      hormone therapy was changed from 2 mg of estradiol (41.7%) compared with 1 mg of
      estradiol (16.7%), 0.625 mg of conjugated estrogen (30%), or tibolone (12.5%).
      Images of breast lesions and fibroids before the switch were assessed, showing no
      change in most women. CONCLUSIONS: This study suggests that TSEC is a good option
      for women who have breast discomfort or persistent bleeding during other hormone
      therapy when taking into account the differences in estrogen dose.

PMID- 30300301
TI  - Age at natural menopause and life expectancy with and without type 2 diabetes.
AB  - OBJECTIVE: Effective interventions of future health care require a better
      understanding of the health risks associated with early onset of menopause and
      diabetes, but the necessary data are scarce. Little quantitative information is
      available about the combined association of early menopause and diabetes on life
      expectancy and the number of years lived with and without diabetes. METHODS: We
      included 3,650 postmenopausal women aged 45+ years from the Rotterdam Study, a
      prospective population-based cohort study. Age at menopause categories were
      defined as follows: early (<=44 y old), normal (45-54 y old), and late (>=55 y
      old). For life table calculations, we used prevalence, incidence rates, and
      hazard ratios for three transitions (free of diabetes to diabetes, free of
      diabetes to death, and diabetes to death) stratifying by age at menopause
      categories and adjusting for confounders. RESULTS: Compared with late menopause,
      the difference in life expectancy for women who experienced early menopause was 
      3.5 (95% CI, -6.6 to -0.8) years overall and -4.6 (95% CI, -8.9 to -0.9) years
      without diabetes. Compared with age at normal menopause, the difference in life
      expectancy for women who experienced early menopause was -3.1 (95% CI, -5.1 to 
      1.1) years overall and -3.3 (95% CI, -6.0 to -0.6) years without diabetes.
      CONCLUSIONS: Women who experienced early menopause lived less long and spent
      fewer years without diabetes than women who experienced normal or late menopause.

PMID- 30300302
TI  - In Reply.

PMID- 30300303
TI  - The Relationship Between Binocular Visual Field Loss and Various Stages of
      Monocular Visual Field Damage in Glaucoma Patients.
AB  - PURPOSE: To investigate the effects of monocular visual field loss severity on
      binocular visual field loss in primary angle-closure glaucoma, primary open angle
      glaucoma and normal tension glaucoma patients. METHODS: In this observational
      cross-sectional study, 250 glaucoma patients and 31 healthy participants were
      assigned to groups according to the stage of monocular visual field loss in both
      eyes; normal, early, moderate or severe. Binocular visual field assessments were
      determined via integrated visual field and Esterman binocular visual evaluations.
      Monocular and binocular visual field parameters were compared within and among
      groups. RESULTS: In patients with one eye at normal or early stage and the other
      at severe stage, the average integrated mean deviations were (mean [SD]), -1.67
      (1.39) dB, and -3.27 (2.05) dB, respectively, and the average Esterman scores
      were >95% (99.17% [1.89%], 96.08% [3.99%], respectively). Where both eyes had
      progressed to moderate or severe damage (moderate/moderate, moderate/severe, or
      severe/severe), the average integrated mean deviations were worse than -6?dB, and
      the mean Esterman scores in the moderate/moderate and the moderate/severe damage
      groups were still >90% (94.20%[5.96%], 94.32%[4.95%], respectively), but it
      dropped rapidly from >90% to 68.44% (26.27%) when both eyes were at severe stage.
      CONCLUSIONS: The binocular visual field can remain relatively intact provided one
      eye is at normal or early stage. Significant binocular visual field defects
      measured by integrated mean deviation were evident when both eyes had progressed
      to moderate or severe stage, and significant Esterman binocular visual field
      defects were only detected when both eyes had advanced to severe stage.

PMID- 30300304
TI  - A Prospective Evaluation of the Repeatability and Reliability of New Steady-state
      Pattern Electroretinogram Parameters.
AB  - PURPOSE: The purpose of this study was to determine the repeatability and
      reproducibility of a new Pattern Electroretinography (PERG) device in healthy
      subjects. METHODS: A total of 40 eyes of 20 healthy subjects (45.6+/-6.8 y, 70%
      female) were enrolled in this prospective study. Steady-state PERG were recorded
      using the Diopsys NOVA (Diopsys Inc., NJ) to obtain the Magnitude, MagnitudeD,
      MagnitudeD/Magnitude Ratio, and Signal to Noise Ratio. Subjects underwent 2
      "contrast sensitivity" protocols with the same electrodes and 2 after changing
      electrodes, by a single examiner. Eyes were stimulated separately using high and
      low contrast patterns. The same examination was repeated by a different operator
      following the same protocol 6 months after the baseline measures. Repeatability
      and reproducibility of the readings were calculated using intraclass correlation
      coefficient (ICC). A Bland-Altman plot was used to analyze the agreement between
      measures. RESULTS: ICC of Magnitude, MagnitudeD, MagnitudeD/Magnitude ratio, and
      SNR were 0.87, 0.81, 0.36, and 0.81, respectively between measures taken with the
      same electrodes (repeatability). After changing electrodes, ICC of the Magnitude,
      MagD, MagD/Mag ratio, and SNR were 0.79, 0.85, 0.51, and 0.83, respectively
      during the same session as baseline measures, and 0.87, 0.85, 0.40, and 0.76 when
      repeated after 6 months (reproducibility). The variability of MagD/Mag ratio
      increased with successive test repetitions. CONCLUSIONS: Mag, MagD, and SNR were
      repeatable and reproducible, whereas the MagD/Mag ratio was less repeatable and
      reproducible. These results suggest that the former parameters are sufficiently
      reliable to be used in clinical practice.

PMID- 30300305
TI  - Associations among Pregnancy, Parturition, and Open-angle Glaucoma: Korea
      National Health and Nutrition Examination Survey 2010-2011.
AB  - PURPOSE: To investigate the association between factors associated with
      parturition and open-angle glaucoma (OAG) in Korean females. METHODS: A
      population-based, cross-sectional survey was performed from the Korean National
      Health and Nutrition Examination Survey from 2010-2011 and enrolled
      postmenopausal female participants (n=1798). We obtained information on
      demographics, comorbidities, and health-related behaviors and performed
      comprehensive ophthalmic examinations. Multivariate regression analysis was used
      to assess the correlation between pregnancy and delivery and the prevalence of
      OAG in all enrolled subjects. RESULTS: The prevalence of OAG among study
      participants was 6.42%. There was a significant difference in the number of
      deliveries and age at first delivery between the OAG group and the non-glaucoma
      group. In multiple linear regression models adjusted for age, hypertension, and
      intraocular pressure only pregnancy 1 was associated with higher risk of OAG
      compared with pregnancy 2 (P=0.023). Subjects who had three or four deliveries
      were at higher risk of OAG compared with subjects with two deliveries (P=0.027).
      An age at first delivery of 16-20 years or 21-23 years was associated with
      increased OAG risk compared with the reference group (P<0.05). CONCLUSIONS: A
      history of three or more deliveries and an age at first delivery younger than 23
      years were associated with increased risk of OAG. These results suggest that
      changes or events during the period from pregnancy to delivery affect the
      development of glaucoma.

PMID- 30300306
TI  - Impact of Head Tilt on Optical Coherence Tomography Image Orientation.
AB  - PURPOSE: Head tilt can have an impact on the orientation of posterior pole
      images. We conducted this study to determine the effect of head tilt on image
      orientation measured by the fovea-Bruch's membrane opening (FoBMO) angle with
      optical coherence tomography (OCT) imaging. METHODS: The study included 56
      healthy subjects with mean (range) age of 33 (18 to 61) years. The dominant eye
      was first determined. To measure head tilt, a smartphone with a built-in
      gyroscope was affixed to the subject's head with adjustable straps. OCT imaging
      was performed in both eyes (in randomized order) at 0, 5, and 10 degrees of head
      tilt in the direction of the imaged eye (ipsilateral head tilt), and then in the
      opposite direction (contralateral head tilt). For each image, the device software
      determined Bruch's membrane opening center and the foveal pit from which the
      FoBMO angle was derived. RESULTS: Thirty-eight (68%) subjects were right eye
      dominant and 18 (32%) were left eye dominant. Each 1 degree head tilt resulted in
      a mean change of 0.76 degree in the FoBMO angle (P<0.01), with no significant
      difference in effect between the 2 eyes (P=0.72). The magnitude of the effect
      increased from 5 to 10 degrees, and was similar for both ipsilateral and
      contralateral head tilt. Ocular dominance did not modulate the effect of head
      tilt (P=0.42). CONCLUSIONS: Head tilt significantly affects OCT image orientation
      as measured by the FoBMO angle, presumably because cyclotorsion is not fully
      compensatory. The magnitude and direction of the effect does not depend on the
      dominant eye.

PMID- 30300307
TI  - Outcomes of Laser Goniopuncture Following Non-penetrating Deep Sclerectomy with
      Mitomycin C: A Large Retrospective Cohort Study.
AB  - PURPOSE: To report on the frequency, efficacy, and safety of laser goniopuncture
      (LGP) in lowering IOP following mitomycin-C augmented non-penetrating deep
      sclerectomy (NPDS) in a large cohort of eyes. METHODS: Monocenter database
      retrospective study. We reviewed records of 350 eyes that underwent NPDS between
      2009 and 2015, at National Ophthalmology Center of XV-XX (Paris, France). We
      recorded incidence of LGP, time between NPDS and LGP, IOP efficacy and the
      occurrence of complications. The success of the LGP was defined by an IOP lower
      than 15?mmHg without hypotonic treatment. RESULTS: Mean postoperative follow-up
      period was 19+/-15.9 months after the NPDS (range:6-58). LGP was performed in 125
      eyes (35.7%) in a mean time after NPDS of 7.4+/-7.6 months (range: 1?d-36?mo).
      Most LGP procedures were performed during the first year (97 eyes, 77.6%). The
      survival analysis using the Kaplan-Meier method showed a 50% incidence of LGP by
      2 years. The mean IOP before LGP was 23.8+/-7.1?mmHg. LGP resulted in immediate
      (Day 8) and significant IOP lowering by up to 15+/-6.8?mmHg. This decrease was
      maintained throughout the follow-up period and the Kaplan-Meier survival success
      rate at two years was 48.9% (95% CI=39.4-60.8). The most common complication was
      iris incarceration which occurred in 22 eyes of 125 LGP (17.6%). CONCLUSIONS:
      Most of the eyes which underwent NPDS may require LGP to reduce IOP to below the
      target value. Most often this procedure was performed in the first year after
      NPDS (77,6%). LGP lowered IOP below 15?mmHg without any hypotonic medication for
      at least two years in 50% of cases. Goniopuncture is associated with potentially
      significant complications, of which the most common is iris incarceration. We
      identified two predicting factors for iris incarceration: high IOP before LGP and
      early LGP after NPDS.

PMID- 30300308
TI  - Panscleritis as an Unusual Complication of Gonioscopy-assisted Transluminal
      Trabeculotomy.
AB  - PURPOSE: To report a case of panscleritis after gonioscopy-assisted transluminal
      trabeculotomy (GATT). METHODS: We describe the case of a 33-year-old man with a
      history of unilateral anterior uveitis and glaucoma, who developed panscleritis
      after GATT surgery. RESULTS: Uneventful GATT surgery was performed in a
      glaucomatous left eye. On the second postoperative day, the patient developed
      tenderness on palpation of the eye. Ophthalmic examination revealed significant
      diffuse hyperemia, elongated and tortuous upper bulbar conjunctival/scleral
      vessels, and exudative retinal detachment at the superior nasal quadrant, with
      diffuse scleral thickening. The patient was diagnosed as having panscleritis,
      which was attributed to the GATT surgery. Although the scleritis resolved
      completely with intravenous and oral methylprednisolone treatment, localized
      retinal detachment persisted. CONCLUSION: Surgery-induced posterior scleritis may
      occur following minimally invasive glaucoma surgeries such as GATT. Control of
      uveitis for at least 3 months prior to surgery is indicated in patients with
      uveitis if GATT surgery is planned.

PMID- 30300310
TI  - World Gastroenterology Organisation (WGO) News and Events.

PMID- 30300309
TI  - Primary Angle Closure Glaucoma with Normal Intraocular Pressure at the First
      Visit: Its Prevalence and Ocular Characteristics.
AB  - PURPOSE: To investigate the prevalence of normal intraocular pressure (IOP) at
      first visit among patients with primary angle closure glaucoma (PACG) and their
      ocular characteristics. PATIENTS AND METHODS: We retrospectively reviewed
      patients with PACG in a referral center. According to untreated IOP, we divided
      PACG eyes into two groups: those with normal IOP and those with high IOP
      (>21?mmHg) at the first visit. RESULTS: One hundred sixty eyes of 160 Korean PACG
      patients were included. Sixty percent (97/160) of the patients had normal IOP at
      their first visit. The PACG patients with initially normal IOP had significantly
      longer axial length (mean+/-standard deviation [SD] 22.99+/-0.76 vs. 22.74+/
      0.61) and deeper "true" anterior chamber depth (ACD) (2.09+/-0.27 vs. 1.82+/
      0.33) than those with initially high IOP (both P<0.05). Multiple logistic
      regression revealed that deeper "true" ACD (per 0.1?mm, odds ratio [OR] 1.38) and
      more hyperopic refractive errors (OR 1.48) were independent predictors of
      initially normal IOP in PACG eyes (P<0.05). The prevalence of disc hemorrhage was
      higher in PACG patients with initially normal IOP than in those with initially
      high IOP (29.9% vs. 14.3%, P=0.029). CONCLUSION: Sixty percent of patients with
      PACG had normal IOP at their first visit. This suggests that without gonioscopy
      clinicians may misdiagnose PACG as normal tension glaucoma. ACD measurement can
      aid the diagnosis of PACG because even PACG eyes with initially normal IOP have
      shallow ACD.

PMID- 30300311
TI  - PROGRESSION OF SCOTOPIC SINGLE-FLASH ELECTRORETINOGRAPHY IN THE STAGES OF CAPN5
      VITREORETINOPATHY.
AB  - PURPOSE: To characterize the changes found in the electroretinography (ERG)
      recordings of patients with autosomal dominant neovascular inflammatory
      vitreoretinopathy and correlate with clinical stages of the disease. METHODS:
      Retrospective chart review. Bright- and dim-flash full-field scotopic, photopic,
      and 30-Hz flicker ERGs were obtained according to international standards. The
      scotopic ERGs were further processed to analyze the oscillatory potential. The
      patient described in the case report underwent full ERG testing; five patients
      composed the archival case series data and included scotopic ERG recordings.
      RESULTS: Stage I autosomal dominant neovascular inflammatory vitreoretinopathy is
      characterized by a decrease in the b-wave amplitude on scotopic flash ERG and the
      disappearance of late OPs; however, the a-wave amplitude is normal. In Stage II,
      attenuation of early OPs and the c-wave are observed in scotopic ERG recordings,
      but both a- and b-wave amplitudes are unchanged. For patients in Stage III, there
      is a continued decline of both a- and b-wave amplitudes in scotopic ERG
      recordings. There was a loss of recordable scotopic ERG response in patients with
      Stage IV disease. CONCLUSION: Electroretinography may be valuable in determining
      optimal timing for therapeutic intervention and response before loss of
      recordable retinal function in CAPN5 vitreoretinopathy.

PMID- 30300312
TI  - PNEUMATIC COMPACTION TREATMENT OF ACUTE SUBFOVEAL HEMORRHAGE AFTER BLUNT TRAUMA
      IN A PATIENT WITH ANGIOID STREAKS ASSOCIATED WITH PSEUDOXANTHOMA ELASTICUM.
AB  - PURPOSE: To report a case of photoreceptor restitution and vision improvement
      with pneumatic compaction treatment of acute subfoveal hemorrhage in a patient
      with angioid streaks associated with pseudoxanthoma elasticum, observed by
      sequential fundus photography, spectral domain optical coherence tomography, and
      fundus autofluorescence. METHODS: Findings on initial and sequential clinical
      examinations, fundus autofluorescence, and spectral domain optical coherence
      tomography are presented, before and after pneumatic compaction, demonstrating
      the course of compaction and resolution of subfoveal hemorrhage and status of the
      foveal ellipsoid zone and external limiting membrane. Sequential improvements in
      oxygen and nutrient diffusion are calculated using Fick's law of diffusion.
      Findings are compared with previous reports regarding the natural history of
      similar patients. RESULTS: Rapid compaction of subfoveal hemorrhage occurred,
      resulting in an 89% improvement in oxygen diffusion in 15 days. No centrifugal
      movement of subfoveal hemorrhage occurred, potentially minimizing photoreceptor
      shearing injury. Ultimately, resorption of all hemorrhage occurred with
      reestablishment of the foveal ellipsoid zone and external limiting membrane and
      minimal juxtafoveal subretinal fibrosis; best-corrected visual acuity improved to
      20/40: an advantage over natural history based on published reports. CONCLUSION:
      Pneumatic compaction in patients with acute subfoveal hemorrhage secondary to
      angioid streaks associated with pseudoxanthoma elasticum compacts subfoveal
      hemorrhage, therefore improving oxygen and nutrient diffusion. This potentially
      spares foveal photoreceptors of ischemic and shearing injury, theoretically
      reducing subfoveal fibrosis and improving vision prognosis in these patients.

PMID- 30300314
TI  - NEUROTROPHIC KERATOPATHY AFTER RETINAL DETACHMENT SURGERY COMBINED WITH ENDOLASER
      PHOTOCOAGULATION.
AB  - PURPOSE: To report neurotrophic keratopathy after vitreoretinal surgery combined
      with aggressive photocoagulation. METHODS: We report a series of three cases with
      neurotrophic keratopathy after pars plana vitrectomy combined with endolaser
      photocoagulation. RESULTS: Three patients who had pars plana vitrectomy with
      different indications were identified. On follow-up, all patients were diagnosed
      with neurotrophic keratopathy. Two of the patients underwent amniotic membrane
      transplantation for the treatment of resistant neurotrophic corneal ulcers.
      CONCLUSION: Neurotrophic keratopathy may occur after pars plana vitrectomy. The
      possible mechanism is long ciliary nerve damage related to the extensive
      endolaser photocoagulation.

PMID- 30300313
TI  - BEARING DOWN ON TREPONEMES: AN ATYPICAL PRESENTATION OF SYPHILITIC UVEITIS.
AB  - PURPOSE: To present an atypical case of syphilis that presented with findings
      concerning for endocarditis and valsalva retinopathy. METHODS: History and
      clinical examination of 42-year-old white man who presented to the emergency
      department with acute onset vision changes associated with gastrointestinal
      symptoms, otalgia, and constitutional symptoms. RESULTS: The review of this case
      highlights the atypical nature in which syphilis can present and can remain
      undiagnosed even in the face of extensive workups for other systemic conditions.
      CONCLUSION: We present a case of syphilis in a patient with multiorgan
      involvement in whom the diagnosis was made based on atypical ocular examination
      findings.

PMID- 30300315
TI  - ADULT-ONSET VITELLIFORM MACULAR DYSTROPHY SECONDARY TO A NOVEL IMPG2 GENE
      VARIANT.
AB  - PURPOSE: To report a case of adult-onset vitelliform macular dystrophy in a
      patient who was found to have a previously unreported variant of the IMPG2 gene.
      METHODS: Case report. RESULTS: A 65-year-old white woman with no significant
      medical or ocular history presented with a complaint of persistent wavy vision
      for 10 months. On funduscopic examination, bilateral vitelliform lesions of
      approximately 1 mm in the right eye and 0.5 mm in the left eye were evident, with
      no choroidal neovascularization in either eye. The patient was diagnosed with
      adult-onset vitelliform macular dystrophy. Genetic testing revealed a single
      likely pathogenic variant of the IMPG2 gene that may explain the examination
      findings. CONCLUSION: Adult-onset vitelliform macular dystrophy is a common and
      relatively benign condition occurring in approximately 1 in 8,000 individuals.
      Although vitelliform lesions can be a manifestation of systemic diseases or be
      idiopathic, in a minority of patients, genetic predisposition may play a role.
      Mutations in four particular genes BEST1, PRPH2, IMPG1, and IMPG2 have been
      associated with some cases of adult-onset vitelliform macular dystrophy, with
      this particular gene variant of IMPG2 being previously unreported.

PMID- 30300316
TI  - Effect of Long-Term Polytrauma on Ventilator-Induced Diaphragmatic Dysfunction in
      a Piglet Model.
AB  - INTRODUCTION: Mechanical ventilation is known to activate oxidative stress and
      proteolytic pathways in the diaphragm. Trauma by inducing inflammation and
      activating proteolytic pathways may potentiate the effects of mechanical
      ventilation on the diaphragm. In a blunt chest trauma with concomitant injuries
      we tested the hypothesis that trauma via inflammation further activates the
      proteolytic pathways and worsens atrophy in the diaphragm. MATERIAL AND METHODS:
      Piglets were separated into 2 groups and underwent 72hrs of mechanical
      ventilation. One group received a polytrauma (PT) by unilateral femur fracture,
      blunt chest trauma with lung contusion, laparotomy with standardized liver
      incision and a predefined haemorrhagic shock. The second mechanically ventilated
      group (MV) did not receive any trauma. A non-ventilated group (Con) served as
      control.Diaphragmatic fibre dimensions, Western Blot analyses of proteolytic
      pathways and lipid peroxidation and mRNA levels of cytokines and NFkB subunit p65
      were measured. RESULTS: Active Caspase-3 was significantly increased in MV (p =
      0.019), and in PT (p = 0.02) compared to Con. NFkB subunit p65, was up-regulated
      in PT (p = 0.010) compared to Con. IL-6 mRNA increased significantly in PT
      compared to Con (p = 0.0024) but did not differ between Con and MV. CONCLUSION:
      Trauma and mechanical ventilation induced proteolysis and atrophy in the
      diaphragm, but only polytrauma induced an inflammatory response in the diaphragm.
      The additional traumatic inflammatory stimulus did not increase the levels of the
      pre-mentioned variables. These data underline that inflammation is not a major
      contributor to VIDD. TRIAL REGISTRY NUMBER: AZ 84-02.04.2014.A265 (Landesamt fur
      Natur-, Umwelt- und Verbraucherschutz, LANUV NRW, Germany).

PMID- 30300317
TI  - A New Echocardiographic Tool for Cardiac Output Evaluation: An Experimental
      Study.
AB  - BACKGROUND: The correlation between cardiac output (CO) evaluated by
      echocardiography and CO measured by thermodilution (COth) varies according to
      different studies. A new transthoracic echocardiography (TTE) tool allows
      automatic calculation of the subaortic velocity time index (VTIauto) and CO
      (COauto). The main objective was to evaluate the correlation between COth and
      COauto in an anesthetized, ventilated piglet hemorrhagic shock (HS) model. The
      secondary objectives were to evaluate the correlation between COth and CO
      evaluated by manual measurements of VTI, and the preload-dependency of VTIvaresp.
      METHODS: Eighteen piglets were bled until mean arterial pressure reached 40 mmHg.
      Controlled hemorrhage was maintained for 30 min before a resuscitation phase. CO
      was measured by Pulse index Contour Cardiac Output (PiCCO) thermodilution
      methods. At each time of the experiment, three VTI values were measured (min,
      med, max) and the average value was calculated. COs were calculated by TTE
      (COmax, COmed, COmin, COave). RESULTS: For the 204 measures attempted, the
      success rate was 197 (97%) manually and 122 (60%) automatically (p < 0.01). The
      correlation coefficients (r) between COth and, respectively, COauto, COave,
      COmax, COmed, and COmin were: 0.83 (95%CI [0.76; 0.88]; p < 0.01), 0.54 (95%CI
      [0.43; 0.63]; p < 0.01), 0.43 (95%CI [0.31; 0.54]; p < 0.01), 0.58 (95%CI [0.48;
      0.67]; p < 0.01), and 0.52 (95%CI [0.41; 0.62]; p < 0.01). CONCLUSION: In an
      experimental model of HS, a new ultrasound tool, COauto, seems better correlated
      with COth than manual echocardiographic measurements.

PMID- 30300318
TI  - Exploring the Protective Role and the Mechanism of Sphingosine 1 Phosphate in
      Endotoxic Cardiomyocytes.
AB  - FTY720 is a sphingosine 1 phosphate (S1P) receptor agonist approved for the
      treatment of multiple sclerosis (MS), which is a chronic inflammatory autoimmune
      disorder. Sepsis is a complex syndrome associated with progressive endotoxemic
      developments, which finally leads to damage of multiple organs, including the
      heart. In critical patients, cardiovascular dysfunction due to sepsis is a major
      cause of death. Previous studies have shown an association between S1P and
      cardioprotection in the situation of ischemia reperfusion and myocardial
      infarction. Therefore, we will study the role of S1P towards endotoxic
      cardiomyocytes. Different doses of FTY720 were applied or not to endotoxic
      cardiomyocytes. The concentration of inflammatory cytokines, including TNF-alpha,
      IL-1beta, IL-6 and IL-10, was measured by enzyme-linked immuno sorbent assay
      (ELISA). Western blotting (WB) was used to analyze the downstream signaling
      pathways. We discovered that FTY720 reduced the levels of TNF-alpha and IL-6
      through the NF-KappaB pathway, inhibited the expression of caspase-3 and
      activated both AKT and ERK1/2. Additionally, the activation of AKT and ERK 1/2
      could be inhibited by the S1P1 and S1P3 receptor antagonist VPC23019. Therefore,
      we infer that S1P exerts a protective effect towards endotoxic cardiomyocytes by
      decreasing the levels of TNF-alpha and IL-6, regulating apoptotic and survival
      signaling pathway. The S1P1 and S1P3 receptors are involved in the prosurvival
      signal activation.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- 30300319
TI  - Comparison of Real-Time and Static Ultrasonography Diagnoses for Detecting
      Incidental Diffuse Thyroid Disease: A Multicenter Study.
AB  - This study aimed to compare diagnostic accuracy of real-time and static
      ultrasonography (US) for differentiating diffuse thyroid disease (DTD) from
      normal thyroid parenchyma (NTP). At 4 participating institutions, 203 patients
      underwent real-time thyroid US before thyroid surgery. For static US, the same
      radiologists retrospectively evaluated US findings on a picture archive and
      communication system after 4 weeks. In real-time and static US diagnoses, US
      category included no DTD, indeterminate, suspicious for DTD, and DTD. We
      investigated the diagnostic accuracy of real-time and static US with a receiver
      operating characteristic curve analysis using histopathologic results as the
      reference standard. Histopathologic results exhibited NTP (n = 139), Hashimoto
      thyroiditis (n = 24), non-Hashimoto lymphocytic thyroiditis (n = 33), and diffuse
      hyperplasia (n = 7). Of 203 patients, there were significant differences in
      echogenicity, echotexture, glandular margin, and vascularity of the thyroid gland
      and US category between NTP and DTD groups in both real-time and static US
      diagnoses (P < 0.001). The diagnostic indices of real-time and static US were
      highest when the cutoff criterion was chosen as 1 or more abnormal US features.
      In addition, US category was the only feature with a significant difference
      between DTD and NTP groups regardless of the practical experience. The receiver
      operating characteristic curve analysis showed that real-time US was superior to
      static US in the diagnostic accuracy; however, there was no significant
      difference (P = 0.09). In conclusion, real-time and static US can be helpful for
      detecting incidental DTD by using US classification based on abnormal US
      features.

PMID- 30300320
TI  - Diagnosing Polyps on Transvaginal Sonography: Is Sonohysterography Always
      Necessary?
AB  - BACKGROUND: Endometrial polyps are localized overgrowth of glands, stroma, and
      blood vessels and reported in 13% to 50% of women with dysfunctional uterine
      bleeding. Transvaginal ultrasound (TVUS) is the initial noninvasive modality of
      choice for the evaluation of endometrial polyps. The addition of intrauterine
      contrast by adding saline during saline infusion sonohysterography (SIS) has been
      reported to improve diagnostic accuracy in detecting of endometrial polyps. Given
      all the technical advances in ultrasound instrumentation and technology over the
      last 10 years, we wanted to revisit the diagnostic accuracy and associated
      confidence level of TVUS and SIS for detecting endometrial polyps. OBJECTIVE: The
      aims of this study was to determine the diagnostic accuracy of TVUS in detecting
      endometrial polyps in patients with abnormal uterine bleeding or infertility and
      to determine if SIS is necessary when the level of confidence that a polyp is
      present is high. MATERIALS AND METHODS: A total of 144 patients who underwent
      both TVUS and SIS for the evaluation of abnormal uterine bleeding and infertility
      were retrospectively identified and independently reviewed by 2 blinded readers.
      Examinations were graded as polyps absent, equivocal for polyps, and polyps
      definitely present. Interreader agreement for TVUS grade was assessed using Cohen
      kappa. Hysteroscopy and histopathology were used as the reference standard for
      the final diagnosis. The sensitivity, specificity, positive predictive value
      (PPV), and negative predictive value were calculated, and confidence intervals
      (CIs) were computed. RESULTS: From the combined assessments of both readers (288
      reads), 24.7% were definitively positive for polyps, 47.2% were negative, and
      28.1% were equivocal by TVUS. Interreader agreement was good with a kappa of 0.66
      (95% CI, 0.56-0.76). Among the 108 reads where hysteroscopy/histopathology
      results were available, even when diagnostic confidence for the presence of
      polyps was high, TVUS had a PPV of 65.2% (95% CI, 42.1%-88.9%). This PPV was
      significantly lower than the corresponding PPV of SIS of 88.5% (95% CI, 77.4
      100.0%; P = 0.021 for the difference). CONCLUSION: Saline infusion
      sonohysterography has better diagnostic accuracy for the detection and exclusion
      of endometrial polyps than TVUS, even in cases where the diagnostic confidence
      for the presence of polyps is high. Saline infusion sonohysterography may still
      be needed to confirm a TVUS diagnosis for polyps to limit the number of negative
      hysteroscopies.

PMID- 30300321
TI  - Assessment of Subclinical Atherosclerosis in Vitamin D Deficiency.
AB  - PURPOSE: Patients with vitamin D deficiency (VDD) have potential to have
      increased cardiovascular morbidity and mortality. In this study, we aimed to
      discover the findings of early atherosclerosis in patients with VDD by measuring
      carotid intima-media thickness (CIMT) and epicardial fat thickness (EFT).
      MATERIALS AND METHODS: The study population includes 52 patients with VDD (n = 30
      [57% female], mean +/- SD age 54.28 +/- 8.77 years, mean +/- SD serum 25
      hydroxyvitamin D (25 [OH] D) 11 +/- 2.4 ng/mL) and 82 participants for control
      group (n = 52 [63.4% female], mean +/- SD age 56.40 +/- 7.90 years, mean +/- SD
      serum (25 [OH] D) 53 +/- 4.2 ng/mL) who have no cardiovascular disease. Carotid
      intima-media thickness was assessed by using ultrasonography, and EFT was
      measured on the free wall of the right ventricle at end diastole from the
      parasternal long-axis views by standard transthoracic 2-dimensional
      echocardiography. RESULTS: Both CIMT and EFT were significantly higher in
      patients with VDD compared with controls (0.75 +/- 0.16 mm vs 0.68 +/- 0.21 mm, P
      < 0.05, and 0.66 +/- 0.15 cm vs 0.56 +/- 0.15 cm, P < 0.001). CONCLUSIONS:
      Patients with VDD seem to have increased CIMT and EFT, which are predictors of
      atherosclerotic process. Further studies are needed to confirm these results.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- 30300322
TI  - Hyperechoic Abdominal Fat: A Sentinel Sign of Inflammation.
AB  - One of the most useful sonographic signs of acute abdominal inflammation is the
      identification of increased echogenicity of the surrounding fat. Hyperechoic fat
      results from vasodilation and edema extending from an adjacent source of
      infection or inflammation. These changes are mediated by such factors such as
      bradykinin, histamine, and various cytokines. The recognition of hyperechoic fat
      on sonography may be an important indicator of the primary source of pathology.
      In addition, it often reflects a more advanced degree of transmural pathology,
      such as "walled-off" perforation of a hollow viscus. This pictorial essay will
      present a variety of examples of hyperechoic inflamed fat involving different
      abdominal organs and will illustrate the diagnostic value of this finding.

PMID- 30300323
TI  - Quantitative Assessment of Palatine Tonsils in Healthy Children and Adolescents
      With Shear-Wave Elastography.
AB  - The normal elasticity and velocity values for palatine tonsils (PTs) in healthy
      children and adolescents were defined using shear wave elastography, and the
      relationship with potential factors affecting these values was assessed. This
      prospective study included a total of 80 cases with ages ranging from 3 to 17
      years. Sex, age, and body mass index (BMI) were recorded. Elasticity and velocity
      measurements of both PTs and the relationship with basic descriptive data were
      investigated. For statistical analyses, independent-samples t tests and Spearman
      rho (r) correlation coefficient were used. Quantitative variables are shown as
      the mean +/- SD, and categorical variables are shown as n (%). The mean age was
      10.6 +/- 6.4 years, and the mean BMI was 17.40 +/- 4 kg/m. The mean elasticity
      and velocity values were 9.38 +/- 1.27 kPa and 1.76 +/- 0.11 m/s for the right PT
      and 9.57 +/- 1.43 kPa and 1.79 +/- 1.04 m/s for the left PT, respectively. The
      mean tonsil volume was 2.44 mL for the right PT and 2.36 mL for the left PT.
      There were no significant differences in elasticity, velocity, and volumes when
      comparing location, age, or sex groups. No significant correlations were observed
      between the elasticity and velocity values and BMI. In conclusion, this
      preliminary work can be used as a reference for the diagnosis of PT diseases.
      Future comprehensive studies are necessary to establish the role of elastography
      in the diagnosis of pathologic tissue differentiation confirmed by clinical,
      laboratory, or pathology analyses.

PMID- 30300324
TI  - Ultrasound Assessment of Acute Kidney Injury.
AB  - Ultrasound assessment of the kidneys in patients with renal impairment has been
      described in various ways in the critical care, nephrology, and radiology
      literature, resulting in a somewhat heterogeneous picture of the gray-scale and
      Doppler ultrasound manifestation of acute kidney injury (AKI). Given that
      ultrasound assessment can potentially identify reversible causes of AKI or
      identify underlying chronic kidney disease, it is important for radiologists to
      be aware of the common etiologies of AKI and the spectrum of ultrasound findings.
      We review the definition and etiologies of renal injury and introduce the
      ultrasound SERVeillance framework-assessment of renal size, echogenicity, renal
      hilum, and vascularity-for the imaging assessment of AKI.

PMID- 30300325
TI  - Difference in Detection Rate of Portal Venous Gas via Computed Tomography and
      Ultrasonography in Pediatric Patients.
AB  - This study was performed to compare computed tomography (CT)- and ultrasonography
      (US)-derived detection rates of portal venous gas (PVG) in pediatric patients and
      investigate whether discrepancies between these modalities were influenced by
      patient age and interval between examinations. We included 25 children who
      underwent both CT and US within 2 days for evaluation of intestinal ischemia.
      McNemar test was used to compare the detection of PVG between the 2 modalities.
      The cohort was retrospectively divided into 2 groups based on whether comparable
      results were obtained via both modalities; the Mann-Whitney U test was used to
      compare patient age and interval between CT and US between these 2 groups. Among
      25 children, CT and US yielded similar results in 17 patients regarding the
      presence or absence of PVG (median age/interval, 2 years [range, 0-17 years]/51
      minutes [range, 2-1196 minutes]; 3/14 detected via both/not both modalities) and
      different results in 8 (median age/interval, 0 years [range, 0-15 years]/171.5
      minutes [range, 64-1486 minutes]; 7/1 detected via US only/via CT only). There
      was a significant difference in PVG detection rate between US and CT (P = 0.034).
      Patient age did not differ significantly between the 2 groups (P = 0.206), but
      the interval between CT and US did (P = 0.025). In conclusion, the detection rate
      of PVG was higher with US, compared with CT, although the timings of the
      examinations could have influenced this finding. Ultrasonography could be useful
      for PVG detection in pediatric patients because it can be performed repeatedly at
      the bedside without radiation exposure.

PMID- 30300326
TI  - New primary immunodeficiency diseases: context and future.
AB  - PURPOSE OF REVIEW: Primary immunodeficiency diseases (PIDs) are genetic disorders
      classically characterized by impaired host defense and an increased
      susceptibility to infections. It is now appreciated that these conditions broadly
      include variations in the genetic code that cause dysregulated immune function.
      This review highlights the newly defined PIDs in the 2017 International Union of
      Immunologic Societies (IUIS) report, current approaches to diagnosing PIDs, and
      the implications for the future management of PIDs. RECENT FINDINGS: With the
      advances in and increased commercial availability of genetic testing and the
      adoption of the TREC assay into the US Newborn Screening program, the number of
      identified PIDs has exponentially risen in the past few decades, reaching over
      350 disorders. The IUIS Inborn Errors of Immunity committee acknowledged at least
      50 new disorders between 2015 and 2017. Furthermore, given the greater
      recognition of disorders with primarily immune dysregulation, the committee
      proposed a more inclusive term of 'inborn errors of immunity' to encompass
      primary immunodeficiencies and immune dysregulation disorders. SUMMARY: This
      latest IUIS report underscores the rapid expansion in the PID field with
      technologic advancements in immunogenetics and clinical screening discovering new
      genetic diseases, and therefore, paving the way to novel therapeutics and
      precision medicine.

PMID- 30300327
TI  - Female athletes: managing risk and maximizing benefit.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an updated summary on
      the unique aspects of caring for female youth and adolescent athletes. RECENT
      FINDINGS: Recent research on female athletes has led to a better understanding of
      injuries and conditions that are more likely to occur in female youth and
      adolescent athletes, including the frequency and severity of concussions,
      musculoskeletal injury such as involving the anterior cruciate ligament, and the
      female athlete triad. Social factors, such as the growing pressure to specialize
      in a sport particularly at an early age, also put young female athletes at risk
      for issues such as overuse injuries. Researchers continue to explore the benefits
      of athletic participation that extend beyond physical fitness. SUMMARY: Female
      participation in youth sports has increased dramatically during the past 50
      years. This has led to greater research on how to manage risks and maximize
      benefits for young female athletes, although there is still much to be learned.
      Providers should educate patients, parents, and coaches on both the increased
      risks for female athletes and ways to provide better support and accessibility of
      youth sports to all children.

PMID- 30300328
TI  - Advances in liver xenotransplantation.
AB  - PURPOSE OF REVIEW: This review highlights advances in liver xenotransplantation,
      focusing on immunologic barriers and mechanisms underlying graft failure and
      recipient demise, and discussion of recent in-vivo results. RECENT FINDINGS: Pig
      to primate models of liver xenotransplantation have been plagued by
      thrombocytopenia, anemia, and coagulopathy. It is now known that platelet
      sequestration is mediated by liver sinusoidal endothelial cells and Kupffer cells
      in part by asialoglycoprotein receptor 1-driven mechanisms. Xenoantigens,
      specifically N-glycolylneuraminic acid, play a role in graft injury as well as
      red blood cell consumption. Finally incompatibilities between coagulation cascade
      molecules contribute to lethal coagulopathy, but can be counteracted with genetic
      modifications and coagulation factor supplementation. Survival has markedly
      increased with this strategy. SUMMARY: An increased understanding of the cellular
      mechanisms responsible for failure of in-vivo pig to primate liver xenotransplant
      models has led to improved outcomes, and this recent success supports initial
      clinical application.

PMID- 30300329
TI  - Infections after xenotransplantation.
AB  - PURPOSE OF REVIEW: Xenotransplantation offers a solution for the global shortage
      of available organs. However, cross-species transplantation and immunosuppression
      raises concerns about transmission of zoonotic infections to the recipient as
      well as to the public. RECENT FINDINGS: Here, we review the major infections of
      concern after xenotransplantation, risks of their transmission, diagnostic,
      therapeutic as well as prevention modalities for these infections after
      xenotransplantation. This review is particularly timely in light of recent
      advances in porcine genome editing technology that allow removal of retroviral
      sequences. SUMMARY: We cannot appreciate the full risk of infections after
      xenotransplantation in absence of clinical trials. However, there are guidelines
      for strict microbiologic monitoring and reporting, infectious diagnostic assay
      development, breeding and quarantine of graft source animals to limit infectious
      transmission.

PMID- 30300330
TI  - Lung bioengineering: advances and challenges in lung decellularization and
      recellularization.
AB  - PURPOSE OF REVIEW: Bioengineering the lung based on its natural extracellular
      matrix (ECM) offers novel opportunities to overcome the shortage of donors, to
      reduce chronic allograft rejections, and to improve the median survival rate of
      transplanted patients. During the last decade, lung tissue engineering has
      advanced rapidly to combine scaffolds, cells, and biologically active molecules
      into functional tissues to restore or improve the lung's main function, gas
      exchange. This review will inspect the current progress in lung bioengineering
      using decellularized and recellularized lung scaffolds and highlight future
      challenges in the field. RECENT FINDINGS: Lung decellularization and
      recellularization protocols have provided researchers with tools to progress
      toward functional lung tissue engineering. However, there is continuous evolution
      and refinement particularly for optimization of lung recellularization. These
      further the possibility of developing a transplantable bioartificial lung.
      SUMMARY: Bioengineering the lung using recellularized scaffolds could offer a
      curative option for patients with end-stage organ failure but its accomplishment
      remains unclear in the short-term. However, the state-of-the-art of techniques
      described in this review will increase our knowledge of the lung ECM and of
      chemical and mechanical cues which drive cell repopulation to improve the
      advances in lung regeneration and lung tissue engineering.

PMID- 30300331
TI  - Mesenchymal stromal cell therapy in intestinal diseases.
AB  - PURPOSE OF REVIEW: The advent of cell therapies, mainly based on the use of
      mesenchymal stromal cells (MSCs), represents a great step forward in the
      treatment of immune-mediated conditions. Here, we focus on those intestinal
      disorders wherein MSCs have been applied for immunotherapeutic purposes and whose
      results are available. RECENT FINDINGS: By virtue of their ability to favour both
      tissue regeneration and immune tolerance, together with a substantial lack of
      immunogenicity, MSCs have gained huge attention in the last decade. Following
      abundant positive experimental data, a sizable number of clinical trials using
      MSCs as a new treatment in chronic inflammatory intestinal diseases were carried
      out with promising results and several are still ongoing. The main indication was
      refractory Crohn's disease wherein both feasibility and safety clearly emerged
      when treating the luminal phenotype with intravenous infusion/s, albeit no
      definitive conclusion on efficacy may be drawn. By contrast, the availability of
      robust demonstration also on the efficacy when treating the fistulizing phenotype
      through local injection/s of MSCs has led to approval of the marketing of an
      industrial preparation (darvadstrocel). SUMMARY: Successful clinical
      implementation of this attractive option is hampered by a number of obstacles
      arising from methodology and regulation issues, which require the institution of
      interdisciplinary task forces before this cell therapy becomes a bedside reality.

PMID- 30300332
TI  - Effects of COMT polymorphism on the cortical processing of vocal pitch
      regulation.
AB  - Recent evidence has shown that auditory-motor integration for speech production
      is influenced by cognitive functions such as working memory and attention,
      suggesting that speech motor control is likely modulated by mechanisms mediated
      by prefrontal regions. Catechol-O-methyltransferase (COMT) gene plays an
      important role in dopamine breakdown in the prefrontal cortex and has been
      associated with a variety of prefrontal cognitive functions. The present event
      related potential study investigated the association between COMT ValMet
      polymorphism and auditory-motor processing of vocal feedback errors. A sample of
      131 Chinese young female adults was genotyped for rs4680 and produced sustained
      vowels while hearing their voice unexpectedly shifted down in pitch by 50 or 200
      cents. The behavioral results showed no effects of COMT ValMet on vocal
      compensations for pitch perturbations. However, individuals with the Met allele
      produced significantly larger P2 responses to -200 cents perturbations than
      individuals with the Val/Val genotype. These results suggest the existence of a
      relationship between COMT ValMet polymorphism and self-monitoring of speech
      feedback errors, and they provide insights into our understanding of the top-down
      modulations of speech motor control mediated by prefrontal regions.

PMID- 30300333
TI  - The potential effect of human chorionic gonadotropin on vasoproliferative
      disorders of the immature retina.
AB  - Human chorionic gonadotropin (hCG) is known to be a powerful vascular endothelial
      growth factor (VEGF)-regulating hormone. It stimulates vascularization of the
      gravid uterus by upregulating VEGF expression. In the body, hCG activates the
      same receptor as luteinizing hormone (LH). Like hCG, LH is also strongly
      proangiogenic. Recently, it has been shown that LH/hCG receptors are present in
      the retina and that both LH and hCG are found in the eye. In fact, the human eye
      can synthesize its own hCG. We have previously shown that LH and VEGF are
      significantly correlated in mammalian eyes, potentially implicating LH
      receptor/hCG-receptor activation in intraocular VEGF regulation. Given that
      elevated VEGF is associated with progression of two vasoproliferative pediatric
      retinal disorders, retinopathy of prematurity and retinoblastoma, our objective
      was to determine whether hCG may potentially affect VEGF production and
      pathologic retinal vascularization in vasoproliferative disorders affecting the
      immature retina. In this study, we used (a) oxygen-induced retinopathy mouse
      model (standard model for retinopathy of prematurity) and (b) Y79 retinoblastoma
      cells (a human cell line derived from immature retinal cells). In the oxygen
      induced retinopathy model, number of preretinal nuclei (representing pathologic
      retinal neovascularization) significantly increases by 57% (P<0.05) in hCG
      treated mice. In Y79 cells, VEGF production significantly increases by 37%
      (P<0.05) in hCG-treated cells. These findings suggest that hCG is potentially
      able to influence retinal vascularization and VEGF production and thus, the hCG
      receptor may potentially represent a therapeutic target for vasoproliferative
      retinal disorders affecting the young eye.

PMID- 30300335
TI  - Highlights in lymphoma from the 2018 American Society of Clinical Oncology annual
      meeting.

PMID- 30300334
TI  - EphA8 is a Prognostic Factor for Oral Tongue Squamous Cell Carcinoma.
AB  - BACKGROUND Oral tongue squamous cell carcinoma (OTSCC) is the most common
      malignancy of the oral cavity. Here we explore the potential effects of EphA8,
      which is one of the receptors in Ephs subfamily of RTKs (receptor tyrosine
      kinases), in the progression and prognosis of OTSCC. MATERIAL AND METHODS A total
      of 119 OTSCC patients were enrolled in this retrospective study.
      Immunohistochemistry (IHC) staining and quantitative polymerase chain reaction (Q
      PCR) were utilized to examine the expression of EphA8 in OTSSC tissues and
      adjacent non-tumor tissues. The relationship between EphA8 expression and the
      clinicopathological features of OTSCC patients were analyzed by chi-square.
      Survival analysis was carried out with Kaplan-Meier curve and the related log
      rank test. Multivariate analysis was then undertaken to assess the prognosis
      factor by utilizing the Cox proportional hazard regression model. In addition,
      MTT assay and Matrigel invasion assay were performed to examine the effects of
      EphA8 on the proliferation and invasion capacities of human oral squamous
      carcinoma cells (SCC-25) and human tongue squamous cell carcinoma cells (H357).
      RESULTS Q-PCR and IHC staining revealed that EphA8 was highly expressed in OTSCC
      tissues, especially in advanced stage OTSCC tissues. Kaplan-Meier curve showed
      that high EphA8 expression was significantly associated with poor prognosis,
      similar to age, smoking habit, drinking habit, tumor size, and TNM stage.
      Multivariate analysis indicated that EphA8 expression could serve as an
      independent prognostic factor in OTSCC. In vitro experiments revealed that
      overexpression of EphA8 might promote the progression of OTSCC via enhancing the
      invasion capacity but not proliferation capacity of tumor cells. CONCLUSIONS
      EphA8 was highly expressed in OTSCC tissues and was significantly associated with
      poor prognosis of OTSCC.

PMID- 30300337
TI  - Advances in aggressive lymphoma from the 2018 American Society of Clinical
      Oncology annual meeting.

PMID- 30300336
TI  - Highlights in lymphoma from the 2018 American Society of Clinical Oncology annual
      meeting: commentary.

PMID- 30300338
TI  - Advances in aggressive lymphoma from the 2018 American Society of Clinical
      Oncology annual meeting: commentary.

PMID- 30300340
TI  - Highlights in chronic lymphocytic leukemia from the 23rd Congress of the European
      Hematology Association.

PMID- 30300339
TI  - Clinical implications of the 2018 iwCLL Guidelines update.

PMID- 30300341
TI  - The neuroanatomy of speech sequencing at the syllable level.
AB  - Correctly ordering a sequence of speech sounds is a crucial aspect of speech
      production. Although studies have yielded a rich body of data on the neural
      substrates of visuomotor sequencing and sequence learning, research on brain
      regions and their functions involving speech sequence production hasn't attracted
      much attention until recently. Previous functional MRI studies manipulating the
      complexity of sequences at the phonemic, syllabic, and suprasyllabic levels have
      revealed a network of motor-related cortical and sub-cortical speech regions. In
      this study, we directly compared human brain activity measured with functional
      MRI during processing of a sequence of syllables compared with the same syllables
      processed individually. Among a network of regions independently identified as
      being part of the sensorimotor circuits for speech production, only the left
      posterior inferior frontal gyrus (pars opercularis, lIFG), the supplementary
      motor area (SMA), and the left inferior parietal lobe (lIPL) responded more
      during the production of syllable sequences compared to producing the same
      syllables articulated one at a time.

PMID- 30300342
TI  - Gene expression in response to optical defocus of opposite signs reveals
      bidirectional mechanism of visually guided eye growth.
AB  - Myopia (nearsightedness) is the most common eye disorder, which is rapidly
      becoming one of the leading causes of vision loss in several parts of the world
      because of a recent sharp increase in prevalence. Nearwork, which produces
      hyperopic optical defocus on the retina, has been implicated as one of the
      environmental risk factors causing myopia in humans. Experimental studies have
      shown that hyperopic defocus imposed by negative power lenses placed in front of
      the eye accelerates eye growth and causes myopia, whereas myopic defocus imposed
      by positive lenses slows eye growth and produces a compensatory hyperopic shift
      in refractive state. The balance between these two optical signals is thought to
      regulate refractive eye development; however, the ability of the retina to
      recognize the sign of optical defocus and the composition of molecular signaling
      pathways guiding emmetropization are the subjects of intense investigation and
      debate. We found that the retina can readily distinguish between imposed myopic
      and hyperopic defocus, and identified key signaling pathways underlying retinal
      response to the defocus of different signs. Comparison of retinal transcriptomes
      in common marmosets exposed to either myopic or hyperopic defocus for 10 days or
      5 weeks revealed that the primate retina responds to defocus of different signs
      by activation or suppression of largely distinct pathways. We also found that 29
      genes differentially expressed in the marmoset retina in response to imposed
      defocus are localized within human myopia quantitative trait loci (QTLs),
      suggesting functional overlap between genes differentially expressed in the
      marmoset retina upon exposure to optical defocus and genes causing myopia in
      humans. These findings identify retinal pathways involved in the development of
      myopia, as well as potential new strategies for its treatment.

PMID- 30300343
TI  - Physicochemical characterization and study of molar mass of industrial gelatins
      by AsFlFFF-UV/MALS and chemometric approach.
AB  - Industrial gelatins have different physicochemical properties that mainly depend
      of the raw materials origin and the extraction conditions. These properties are
      closely related to the molar mass distribution of these gelatins. Several methods
      exist to characterize molar mass distribution of polymer, including the
      Asymmetrical Flow Field Flow Fractionation method. The goal of this study is to
      analyze the relationship between physicochemical properties and the gelatins
      molar mass distribution obtained by Asymmetrical Flow Field Flow Fractionation.
      In this study, 49 gelatins samples extracted from pig skin are characterized in
      terms of gel strength and viscosity and their molar mass distribution are
      analyzed by Asymmetrical Flow Field Flow Fractionation coupled to an Ultraviolet
      and Multi Angle Light Scattering detector. This analytical method is an
      interesting tool for studying, simultaneously, the primary chains and the high
      molar-mass fraction corresponding to the polymer chains. Correlation analysis
      between molar mass distribution data from the different fractions highlights the
      importance of high molar mass polymer chains to explain the gel strength and
      viscosity of gelatins. These results are confirmed by an additional chemometric
      approach based on the UV absorbance of gelatin fractograms to predict gel
      strength (r2Cal = 0.85) and viscosity (r2Cal = 0.79).

PMID- 30300345
TI  - Climate communication for biologists: When a picture can tell a thousand words.
AB  - Pictures often tell a story better than the proverbial 1,000 words. However, in
      connection with climate change, many pictures can be highly misleading, for
      example, when a snowball is used to ridicule the notion of global warming or when
      a picture of a dead crop is supposed to alert people to climate change. We
      differentiate between such inappropriate pictures and those that can be used
      legitimately because they capture long-term trends. For example, photos of a
      glacier's retreat are legitimate indicators of the long-term mass balance loss
      that is observed for the vast majority of glaciers around the world.

PMID- 30300346
TI  - Confronting climate change in the age of denial.
AB  - This Editorial introduces a Collection of articles in which the authors explore
      the challenges and pitfalls of communicating the science of climate change in an
      atmosphere where evidence doesn't matter.

PMID- 30300344
TI  - Ran GTPase, an eukaryotic gene novelty, is involved in amphioxus mitosis.
AB  - Ran (ras-related nuclear protein) is a small GTPase belonging to the RAS
      superfamily that is specialized in nuclear trafficking. Through different
      accessory proteins, Ran plays key roles in several processes including nuclear
      import-export, mitotic progression and spindle assembly. Consequently, Ran
      dysfunction has been linked to several human pathologies. This work illustrates
      the high degree of amino acid conservation of Ran orthologues across evolution,
      reflected in its conserved role in nuclear trafficking. Moreover, we studied the
      evolutionary scenario of the pre-metazoan genetic linkage between Ran and Stx,
      and we hypothesized that chromosomal proximity of these two genes across
      metazoans could be related to a regulatory logic or a functional linkage. We
      studied, for the first time, Ran expression during amphioxus development and
      reported its presence in the neural vesicle, mouth, gill slits and gut
      corresponding to body regions involved in active cell division.

PMID- 30300347
TI  - A genome size and phylogenetic survey of Mediterranean Tripleurospermum and
      Matricaria (Anthemideae, Asteraceae).
AB  - The study of genome size variation can contribute valuable information on species
      relationships as well as correlate to several morphological or ecological
      features, among others. Here we provide an extensive report on genome sizes on
      genus Tripleurospermum and its closely related genus Matricaria, which are two
      typically Mediterranean genera particularly widespread and diverse in Turkey, the
      origin of most of the populations here studied. We analyse and discuss genome
      size variation in the first relatively complete molecular phylogenetic framework
      of Tripleurospermum (based on ITS and ETS ribosomal DNA-rDNA-regions). We find
      cases of intraspecific genome size variation, which could be taxonomically
      significant. Genome downsizing is also detected as the typical response to
      polyploidisation in Tripleurospermum taxa, being most conspicuous at the
      tetraploid level. Several positive correlations with genome size, including those
      with pollen and stomatal size or cypsela length, among others, are also found.
      Remarkably, taxa presenting rhizomes tend to present higher genome sizes,
      confirming a trend to accumulate nuclear DNA in such species, which could be
      explained by the nutrient reserves availability in their storage organs, allowing
      genome expansion, or by the lower rates of sexual reproduction in rhizomatous
      taxa.

PMID- 30300348
TI  - Association of plasma and urine viscosity with cardiometabolic risk factors and
      oxidative status. A pilot study in subjects with abdominal obesity.
AB  - There is increasing interest in the search for accurate, repeatable and widely
      applicable clinical biomarkers for the early detection of cardiometabolic
      alterations and oxidative status. Viscosity is a promising tool in that sense,
      although most studies have used simple viscosimeters, providing limited
      information, and have not considered oxidative status. The aim of this study was
      to assess whether viscosity determinations were associated with cardiometabolic
      and oxidative status in subjects at a primary stage of cardiometabolic risk. A
      pilot study (n = 20) was conducted in subjects with abdominal obesity,
      determining urine and plasma viscosity with a rotational rheometer at different
      shear rates (10000-1000 s-1 in plasma and 1000-50 s-1 in urine). Simple
      regression showed that urine viscosity was significantly (p< 0.05) associated
      with markers of oxidative status, and plasma viscosity with blood glucose.
      Categorical Principal Component Analysis plots showed that urine viscosity
      measurements at different shear rates clustered in three groups (low,
      intermediate and high shear rates) were selectively associated with uric acid,
      polyphenols and antioxidant capacity respectively. Plasma viscosity did not seem
      to be a relevant clinical marker in subjects with abdominal obesity. Therefore,
      urine viscosity could potentially serve as a complimentary marker in the
      evaluation of oxidative status.

PMID- 30300350
TI  - Tracking arctic marine mammal resilience in an era of rapid ecosystem alteration.
AB  - Global warming is significantly altering arctic marine ecosystems. Specifically,
      the precipitous loss of sea ice is creating a dichotomy between ice-dependent
      polar bears and pinnipeds that are losing habitat and some cetaceans that are
      gaining habitat. While final outcomes are hard to predict for the many and varied
      marine mammal populations that rely on arctic habitats, we suggest a simplified
      framework to assess status, based upon ranking a population's size, range,
      behavior, and health. This basic approach is proposed as a means to prioritize
      and expedite conservation and management efforts in an era of rapid ecosystem
      alteration.

PMID- 30300349
TI  - The effect of parasite infection on the recombination rate of the mosquito Aedes
      aegypti.
AB  - Sexual reproduction and meiotic recombination generate new genetic combinations
      and may thereby help an individual infected by a parasite to protect its
      offspring from being infected. While this idea is often used to understand the
      evolutionary forces underlying the maintenance of sex and recombination, it also
      suggests that infected individuals should increase plastically their rate of
      recombination. We tested the latter idea with the mosquito Aedes aegypti and
      asked whether females infected by the microsporidian Vavraia culicis were more
      likely to have recombinant offspring than uninfected females. To measure the rate
      of recombination over a chromosome we analysed combinations of microsatellites on
      chromosome 3 in infected and uninfected females, in the (uninfected) males they
      copulated with and in their offspring. As predicted, the infected females were
      more likely to have recombinant offspring than the uninfected ones. These results
      show the ability of a female to diversify her offspring in response to parasitic
      infection by plastically increasing her recombination rate.

PMID- 30300352
TI  - Contribution of social factors to maternal deaths in urban India: Use of care
      pathway and delay models.
AB  - This paper uses care pathway and delay models to better understand the possible
      social reasons for maternal deaths in a city with good public and private health
      infrastructure. The findings can inform programmes to reduce maternal mortality.
      During 2007-15, 136 maternal deaths were reported in Chandigarh, India. Using
      World Health Organisation's verbal autopsy questionnaire, interviews were
      conducted with primary caregivers of 68 (50%) of the 136 deceased women, as
      majority of the families had returned to their native places. We used process
      tracing techniques to construct the care pathways and identify delays, and
      explored open-ended responses using thematic analysis. The mean age of the
      deceased women was 27 years, 51% resided in slums, 32% were primigravida, 25% had
      their deliveries assisted by traditional birth attendants, and 23% had Caesarean
      section. Eight percent died at home, and 54% died in tertiary level facilities.
      Post-partum haemorrhage (26.5%), and complications of puerperium (25%) and
      labour/delivery (14.7%) were the reported medical causes. Male child preference
      and norms for home delivery were identified as the distal socio-cultural causes.
      Individual and family level factors included: shame on multiple pregnancies; fear
      of discrimination from providers; past successful deliveries at home leading to
      overconfidence and not seeking institutional care; and lack of awareness about
      family planning, antenatal care, and danger signs of pregnancy. Healthcare system
      factors were: non-availability of senior doctors at the time of consultation in
      the emergency that delayed initiation of immediate treatment, and lack of
      availability of life-saving equipment due to patient load. Empirical evidence was
      found on social causes of maternal deaths, which could have been prevented by
      appropriate actions at individual, family, societal, institutional and policy
      levels. This study identified potential preventable causes of primarily social
      origin, which could help in taking actionable steps at several levels to further
      reduce maternal deaths in India.

PMID- 30300351
TI  - Retention in HIV care during the 3 years following release from incarceration: A
      cohort study.
AB  - BACKGROUND: Sustained retention in HIV care (RIC) and viral suppression (VS) are
      central to US national HIV prevention strategies, but have not been
      comprehensively assessed in criminal justice (CJ) populations with known health
      disparities. The purpose of this study is to identify predictors of RIC and VS
      following release from prison or jail. METHODS AND FINDINGS: This is a
      retrospective cohort study of all adult people living with HIV (PLWH)
      incarcerated in Connecticut, US, during the period January 1, 2007, to December
      31, 2011, and observed through December 31, 2014 (n = 1,094). Most cohort
      participants were unmarried (83.7%) men (77.0%) who were black or Hispanic
      (78.1%) and acquired HIV from injection drug use (72.6%). Prison-based pharmacy
      and custody databases were linked with community HIV surveillance monitoring and
      case management databases. Post-release RIC declined steadily over 3 years of
      follow-up (67.2% retained for year 1, 51.3% retained for years 1-2, and 42.5%
      retained for years 1-3). Compared with individuals who were not re-incarcerated,
      individuals who were re-incarcerated were more likely to meet RIC criteria (48%
      versus 34%; p < 0.001) but less likely to have VS (72% versus 81%; p = 0.048).
      Using multivariable logistic regression models (individual-level analysis for
      1,001 individuals after excluding 93 deaths), both sustained RIC and VS at 3
      years post-release were independently associated with older age (RIC: adjusted
      odds ratio [AOR] = 1.61, 95% CI = 1.22-2.12; VS: AOR = 1.37, 95% CI = 1.06-1.78),
      having health insurance (RIC: AOR = 2.15, 95% CI = 1.60-2.89; VS: AOR = 2.01, 95%
      CI = 1.53-2.64), and receiving an increased number of transitional case
      management visits. The same factors were significant when we assessed RIC and VS
      outcomes in each 6-month period using generalized estimating equations (for 1,094
      individuals contributing 6,227 6-month periods prior to death or censoring).
      Additionally, receipt of antiretroviral therapy during incarceration (RIC: AOR =
      1.33, 95% CI 1.07-1.65; VS: AOR = 1.91, 95% CI = 1.56-2.34), early linkage to
      care post-release (RIC: AOR = 2.64, 95% CI = 2.03-3.43; VS: AOR = 1.79; 95% CI =
      1.45-2.21), and absolute time and proportion of follow-up time spent re
      incarcerated were highly correlated with better treatment outcomes. Limited data
      were available on changes over time in injection drug use or other substance use
      disorders, psychiatric disorders, or housing status. CONCLUSIONS: In a large
      cohort of CJ-involved PLWH with a 3-year post-release evaluation, RIC diminished
      significantly over time, but was associated with HIV care during incarceration,
      health insurance, case management services, and early linkage to care post
      release. While re-incarceration and conditional release provide opportunities to
      engage in care, reducing recidivism and supporting community-based RIC efforts
      are key to improving longitudinal treatment outcomes among CJ-involved PLWH.

PMID- 30300353
TI  - The placenta goes viral: Retroviruses control gene expression in pregnancy.
AB  - The co-option of endogenous retroviruses (ERVs) is increasingly recognized as a
      recurrent theme in placental biology, which has far-reaching implications for our
      understanding of mammalian evolution and reproductive health. Most research in
      this area has focused on ERV-derived proteins, which have been repeatedly co
      opted to promote cell-cell fusion and immune modulation in the placenta. ERVs
      also harbor regulatory sequences that can potentially control placental gene
      expression, but there has been limited evidence to support this role. In a recent
      study, Dunn-Fletcher and colleagues discover a striking example of an ERV-derived
      enhancer element that has been co-opted to regulate a gene important for human
      pregnancy. Using genomic and experimental approaches, they firmly establish that
      a primate-specific ERV functions as a placenta-specific enhancer for
      corticotropin-releasing hormone (CRH), a hormone linked to the control of birth
      timing in humans. Their findings implicate an extensive yet understudied role for
      retroviruses in shaping the evolution of placental gene regulatory networks.

PMID- 30300354
TI  - (Escaping) the paradox of scientific storytelling.
AB  - Compelling stories about science can motivate people to engage and respond to
      relevant problems facing society. While science plays a unique role in society,
      providing the best available evidence for policy choices, understanding the
      world, and informing citizens' daily lives, it does not hold any intrinsic
      advantage in creating captivating stories for mass audiences. Instead, science
      must compete with other storytellers, many of whom are not bound to scientific
      evidence. This presents a paradox-how can science preserve its credibility as
      curator of knowledge while engaging audiences with a communication format that is
      agnostic to truth?

PMID- 30300355
TI  - Strawberry seed extract and its major component, tiliroside, promote ceramide
      synthesis in the stratum corneum of human epidermal equivalents.
AB  - The activation of peroxisomeproliferator-activated receptor (PPAR) alpha can
      stimulate the expression of ceramide-related enzymes, and a major component of
      strawberry seed extract (SSE) tiliroside enhances the expression of PPARalpha. We
      determined whether SSE and tiliroside may stimulate ceramide synthesis in the
      stratum corneum (SC) of the human epidermal equivalents (HEEs) culture model.
      Treatment with SSE at 1.0 and 3.0 MUg/mL elicited a significant increase in the
      total ceramide content in the SC, which was accompanied by a significant increase
      in almost all ceramide species except for ceramide [EOS] and [AP]. Treatment with
      tiliroside at 0.3 MUg/mL slightly accentuated the total ceramide content in the
      SC together with a significant increase in the ceramide [NS, NDS] content.
      Messenger RNA analysis demonstrated that SSE at 1 or 3 MUg/mL significantly
      stimulated the gene expression of serine palmitoyltransferase (SPT) 2, ceramide
      synthase (CerS) 3, glucosylceramide synthase (GCS), and beta-glucocerebrosidase
      (GBA) but not of SPT1, sphingomyelin synthase (SMS) 1/2 and acid sphingomyelinase
      (ASM). In contrast, tiliroside elicited significant increases in the gene
      expression levels of GCS and GBA only at 0.3 and/or 0.1 MUg/mL. Western blotting
      analysis revealed that both SSE and tiliroside enhanced the protein expression
      levels of GCS and GBA but not of SPT2 at 1 or 3 and 0.1 or 0.3 MUg/mL,
      respectively. These findings suggested that both SSE and tiliroside have a
      distinct potential to stimulate the level of ceramide [NS, NDS] in the SC by
      enhancing the expression of GCS and GBA. The higher stimulatory effect with SSE
      than tiliroside on SC ceramide synthesis correlates with the significant increase
      observed with SSE but not tiliroside in the gene expression levels of SPT2 and
      CerS3. Therefore, it is anticipated that SSE is effective in improving skin
      barrier function and moisture retention in several ceramide-deficit skin
      conditions, including surfactant-induced roughened skin, xerosis, and atopic
      dermatitis.

PMID- 30300356
TI  - Human posterior parietal and dorsal premotor cortex encode the visual properties
      of an upcoming action.
AB  - Behavioral studies show that motor actions are planned by adapting motor programs
      to produce desired visual consequences. Does this mean that the brain plans these
      visual consequences independent of the motor actions required to obtain them?
      Here we addressed this question by investigating planning-related fMRI activity
      in human posterior parietal (PPC) and dorsal premotor (PMd) cortex. By
      manipulating visual movement of a virtual end-effector controlled via button
      presses we could dissociate motor actions from their sensory outcome. A clear
      representation of the visual consequences was visible in both PPC and PMd
      activity during early planning stages. Our findings suggest that in both PPC and
      PMd action plans are initially represented on the basis of the desired sensory
      outcomes while later activity shifts towards representing motor programs.

PMID- 30300357
TI  - Penetration and scattering-Two optical phenomena to consider when applying
      proximal remote sensing technologies to object classifications.
AB  - Proximal remote sensing is being used across a very wide range of research fields
      and by scientists, who are often without deep theoretical knowledge optical
      physics; the author of this article falls squarely in that category! This article
      highlights two optical phenomena, which may greatly influence the quality and
      robustness of proximal remote sensing: penetration and scattering. Penetration
      implies that acquired reflectance signals are associated with both physical and
      chemical properties of target objects from both the surface and internal
      tissues/structures. Scattering implies that reflectance signals acquired from one
      point or object are influenced by scattered radiometric energy from neighboring
      points or objects. Based on a series of laboratory experiments, penetration and
      scattering were discussed in the context of "robustness" (repeatability) of
      hyperspectral reflectance data. High robustness implies that it is possible to
      control imaging conditions and therefore: 1) obtain very similar radiometric
      signals from inert objects (objects that do not change) over time, and 2) be able
      to consistently distinguish objects that are otherwise highly similar in
      appearance (size, shape, and color) and in terms of biochemical composition. It
      was demonstrated that robustness of hyperspectral reflectance data (40 spectral
      bands from 385 to 1024 nm) were significantly influenced by penetration and
      scattering of radiometric energy. In addition, it was demonstrated that the
      influence of penetration and scattering varied across the examined spectrum.
      Characterization of how optical phenomena may affect the robustness of
      reflectance data is important when using proximal remote sensing technologies as
      tools used to classify engineering and biological objects.

PMID- 30300358
TI  - Adherence to etanercept therapy in rheumatoid arthritis patients during 3 years
      of follow-up.
AB  - OBJECTIVES: To determine the percentage non-adherence to etanercept in patients
      with rheumatoid arthritis during three years of follow-up. METHODS: During study
      visits in this prospective cohort study, blood samples were taken to determine
      serum etanercept concentrations using ELISA and patients were asked if they had
      missed an etanercept dose, at which date and for what reason. Non-adherence was
      defined as serum etanercept concentration <0.1 MUg/mL and no valid reason to miss
      the prescribed etanercept dose. RESULTS: In total, 292 consecutive patients
      treated with etanercept were included. Most patients had a valid reason to miss
      their etanercept dose (25/37). In total 12 out of 292 patients (4.1%, 95%
      confidence interval 2.2-7.2) were non-adherent during the 3 year period. In a
      small percentage of patients (3.4%, 95% confidence interval 0.8-10.4) who failed
      to respond to etanercept therapy, according to their rheumatologist, this was
      associated with inadequate exposure to etanercept and thus non-adherence.
      CONCLUSION: In this study, adherence to etanercept therapy was measured using
      serum etanercept concentration. In most patients an absent etanercept
      concentration was due to a medical reason. Furthermore, the majority of patients
      were adherent to etanercept therapy and had adequate drug exposure. In total,
      only 12 out of 292 patients (4.1%) were non-adherent during 3 years of follow-up.
      These findings highlight that only a small minority of patients are non-adherent
      to etanercept treatment, especially compared to adherence rates of other drugs.
      However, physicians should be aware that in patients failing to respond to
      treatment, non-adherence is a possible cause.

PMID- 30300359
TI  - Identification of Leptospira and Bartonella among rodents collected across a
      habitat disturbance gradient along the Inter-Oceanic Highway in the southern
      Amazon Basin of Peru.
AB  - BACKGROUND: The southern Amazon Basin in the Madre de Dios region of Peru has
      undergone rapid deforestation and habitat disruption, leading to an unknown
      zoonotic risk to the growing communities in the area. METHODOLOGY/PRINCIPAL
      FINDINGS: We surveyed the prevalence of rodent-borne Leptospira and Bartonella,
      as well as potential environmental sources of human exposure to Leptospira, in 4
      communities along the Inter-Oceanic Highway in Madre de Dios. During the rainy
      and dry seasons of 2014-2015, we captured a total of 97 rodents representing 8
      genera in areas that had experienced different degrees of habitat disturbance.
      Primarily by using 16S metagenomic sequencing, we found that most of the rodents
      (78%) tested positive for Bartonella, whereas 24% were positive for Leptospira;
      however, the patterns differed across seasons and the extent of habitat
      disruption. A high prevalence of Bartonella was identified in animals captured
      across both trapping seasons (72%-83%) and the relative abundance was correlated
      with increasing level of land disturbance. Leptospira-positive animals were more
      than twice as prevalent during the rainy season (37%) as during the dry season
      (14%). A seasonal fluctuation across the rainy, dry, and mid seasons was also
      apparent in environmental samples tested for Leptospira (range, 55%-89% of
      samples testing positive), and there was a high prevalence of this bacteria
      across all sites that were sampled in the communities. CONCLUSIONS/SIGNIFICANCE:
      These data indicate the need for increased awareness of rodent-borne disease and
      the potential for environmental spread along the communities in areas undergoing
      significant land-use change.

PMID- 30300360
TI  - Blood outgrowth endothelial cells (BOECs) as a novel tool for studying adhesion
      of Plasmodium falciparum-infected erythrocytes.
AB  - The lack of suitable animal models for the study of cytoadhesion of P. falciparum
      infected erythrocytes (IEs) has necessitated in vitro studies employing a range
      of cell lines of either human tumour origin (e.g., BeWo and C32 cells) or non
      human origin (e.g., CHO cells). Of the human cells available, many were isolated
      from adults, or derived from a pool of donors (e.g., HBEC-5i). Here we
      demonstrate, for the first time, the successful isolation of blood outgrowth
      endothelial cells (BOECs) from frozen stabilates of peripheral blood mononuclear
      cells obtained from small-volume peripheral blood samples from paediatric malaria
      patients. BOECs are a sub-population of human endothelial cells, found within the
      peripheral blood. We demonstrate that these cells express receptors such as
      Intercellular Adhesion Molecule 1 (ICAM-1/CD54), Endothelial Protein C Receptor
      (EPCR/CD201), platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31),
      Thrombomodulin (CD141), and support adhesion of P. falciparum IEs.

PMID- 30300361
TI  - Measures matter: A scoping review of maternal and newborn indicators.
AB  - BACKGROUND: A variety of global-level monitoring initiatives have recommended
      indicators for tracking progress in maternal and newborn health. As a first step
      supporting the work of WHO's Mother and Newborn Information for Tracking Outcomes
      and Results (MoNITOR) Technical Advisory Group, we aimed to compile and
      synthesize recommended indicators in order to document the landscape of maternal
      and newborn measurement and monitoring. METHODS: We conducted a scoping review of
      indicators proposed by global multi-stakeholder groups to suggest next steps to
      further support maternal and newborn measurement and monitoring. Indicators
      pertaining to pregnancy, childbirth, and postpartum/postnatal and newborn care
      were extracted and included in the indicator compilation, together with key
      indicator metadata. We examined patterns and relationships across the compiled
      indicators. RESULTS: We identified 140 indicators linked to maternal and newborn
      health topics across the continuum of service provision. Fifty-five indicators
      relate to inputs and processes, 30 indicators relate to outputs, outcomes
      comprise 37 indicators in the database, and 18 impact indicators. A quarter of
      indicators proposed by global groups is either under development/discussion or is
      considered "aspirational", highlighting the currently evolving monitoring
      landscape. Although considerable efforts have been made to harmonize indicator
      recommendations, there are still relatively few indicators shared across key
      monitoring initiatives and some of those that are shared may have definitional
      variation. CONCLUSION: Rapid, wide-ranging work by a number of multi-stakeholder
      groups has resulted in a substantial number of indicators, many of which
      partially overlap and many are not supported with adequate documentation or
      guidance. The volume of indicators, coupled with the number of initiatives
      promoting different indicator lists, highlight the need for strengthened
      coordination and technical leadership to harmonize recommendations for improved
      measurement and monitoring of data related to maternal and newborn heath.

PMID- 30300362
TI  - An efficient dynamic ID-based remote user authentication scheme using self
      certified public keys for multi-server environments.
AB  - Recently, Li et al. proposed a novel smart card and dynamic ID-based remote user
      authentication scheme for multi-server environments. They claimed that their
      scheme can resist several types of attacks. However, through careful analysis, we
      find that Li et al.'s scheme is vulnerable to stolen smart card and off-line
      dictionary attacks, replay attacks, impersonation attacks and server spoofing
      attacks. By analyzing other similar schemes, we find that a certain type of
      dynamic ID-based multi-server authentication scheme in which only hash functions
      are used and whereby no registration center participates in the authentication
      and session key agreement phase faces difficulties in providing perfectly
      efficient and secure authentication. To compensate for these shortcomings, we
      propose a novel dynamic ID-based remote user authentication scheme for multi
      server environments based on pairing and self-certified public keys. Security and
      performance analyses show that the proposed scheme is secure against various
      attacks and has many excellent features.

PMID- 30300363
TI  - Intrinsic activation of the vitamin D antimicrobial pathway by M. leprae
      infection is inhibited by type I IFN.
AB  - Following infection, virulent mycobacteria persist and grow within the
      macrophage, suggesting that the intrinsic activation of an innate antimicrobial
      response is subverted by the intracellular pathogen. For Mycobacterium leprae,
      the intracellular bacterium that causes leprosy, the addition of exogenous innate
      or adaptive immune ligands to the infected monocytes/macrophages was required to
      detect a vitamin D-dependent antimicrobial activity. We investigated whether
      there is an intrinsic immune response to M. leprae in macrophages that is
      inhibited by the pathogen. Upon infection of monocytes with M. leprae, there was
      no upregulation of CYP27B1 nor its enzymatic activity converting the inactive
      prohormone form of vitamin D (25-hydroxyvitamin D) to the bioactive form
      (1,25alpha-dihydroxyvitamin D). Given that M. leprae-induced type I interferon
      (IFN) inhibited monocyte activation, we blocked the type I IFN receptor (IFNAR),
      revealing the intrinsic capacity of monocytes to recognize M. leprae and
      upregulate CYP27B1. Consistent with these in vitro studies, an inverse
      relationship between expression of CYP27B1 vs. type I IFN downstream gene OAS1
      was detected in leprosy patient lesions, leading us to study cytokine-derived
      macrophages (MPhi) to model cellular responses at the site of disease. Infection
      of IL-15-derived MPhi, similar to MPhi in lesions from the self-limited form of
      leprosy, with M. leprae did not inhibit induction of the vitamin D antimicrobial
      pathway. In contrast, infection of IL-10-derived MPhi, similar to MPhi in lesions
      from patients with the progressive form of leprosy, resulted in induction of type
      I IFN and suppression of the vitamin D directed pathway. Importantly, blockade of
      the type I IFN response in infected IL-10 MPhi decreased M. leprae viability.
      These results indicate that M. leprae evades the intrinsic capacity of human
      monocytes/MPhi to activate the vitamin D-mediated antimicrobial pathway via the
      induction of type I IFN.

PMID- 30300364
TI  - Safety of intrauterine devices in MRI.
AB  - OBJECTIVES: The paucity of safety information on intrauterine devices (IUD) for
      magnetic resonance imaging (MRI) examinations is clinically relevant. The aim of
      this study is to evaluate the MRI safety of clinically used IUDs composed of
      copper/gold and stainless steel at 1.5T and 3.0T. MATERIALS AND METHODS: We
      assessed and compared the displacement force, torque effects, presence of imaging
      artifacts and heating of IUDs composed of copper/gold (western IUDs) and
      stainless steel (China) on 1.5 and 3.0T MRI systems. RESULTS: Gold/Copper IUDs
      can show small deflection angles of 7 degrees  +/- 7 degrees  in the worst-case
      field gradient of 40T/m (equivalent to magnetic force of 0.5 mN), while the
      stainless steel IUD experienced significant magnetic force and deflection (Force
      > 7.5 N; deflection angle 90 degrees  +/- 1 degrees ). Manual rotation and
      suspension method show no torque effects on gold/copper IUDs but high torque
      effects were observed by manual rotation on the stainless steel IUD. Heating
      measurements showed a temperature increase (rescaled to a wbSAR of 4 W/kg) of 1.4
      degrees C at 1.5T / 3.4 degrees C at 3.0 T (stainless steel IUD), 3.2 degrees C
      at 1.5 T / 3.8 degrees C at 3 T (copper/gold IUD), 3.3 degrees C at 1.5 T / 4.8
      degrees C at 3 T (copper 1), 3.8 degrees C at 1.5 T / 4.8 degrees C at 3 T
      (copper 2). The visible imaging artifacts of the copper and gold IUDs at 3 T MRI
      reach a diameter of 4 mm +/- 1 mm, while the stainless steel IUD resulted in
      artifacts measuring 200mm +/- 10 mm when using gradient echo pulse sequences.
      CONCLUSIONS: Standard IUDs (copper/gold) can be considered as conditional for MR
      safety at 1.5 T and 3.0 T, demonstrating at wbSAR up to 4W/kg and a magnetic
      field gradient of up to 40T/m with minimal imaging artifacts. The stainless steel
      IUD, however, induces unacceptable artifacts and is potentially harmful to
      patients during MRI due to high magnetic dislocation forces and torque (MR
      unsafe).

PMID- 30300365
TI  - The degree of altriciality and performance in a cognitive task show correlated
      evolution.
AB  - Previous comparative research on the evolution of cognition has tested what we
      call the "altricial intelligence hypothesis". This posits that a relationship
      between evolutionary changes in the altricial period length and cognition exists
      across animal species. However, the evidence available thus far either comes from
      indirect measurements of cognition or has not been conclusive. We performed a
      phylogenetic analysis of published data from various sources on 31 homeothermic
      species to test for an evolutionary association between the degree of
      altriciality and a direct measure of self-control. For each species, the degree
      of altriciality was determined based on the residual altricial period (i.e., the
      time from birth to fledging in birds and to weaning in mammals) on lifespan. The
      percentage of success in the cylinder task was the measure of self-control. Our
      results showed that the degree of altriciality covaried positively with the
      measure of self-control. Based on the results of this study, we sustain that
      evolutionary changes in the length of the altricial period are associated with
      evolutionary changes in the cognitive system used by homeotherms to perform the
      cylinder task.

PMID- 30300366
TI  - Killed Propionibacterium acnes enhances immunogenicity and tumor growth control
      of a dendritic-tumor cell hybrid vaccine in a murine melanoma model.
AB  - Hybrid vaccines have been investigated in clinical and experimental studies once
      expresses total antigens of a tumor cell combined with the ability of a dendritic
      cell (DC) to stimulate immune responses. However, the response triggered by these
      vaccines is often weak, requiring the use of adjuvants to increase vaccine
      immunogenicity. Killed Propionibacterium acnes (P. acnes) exerts immunomodulatory
      effects by increasing the phagocytic and tumoricidal activities of macrophages,
      promoting DC maturation, inducing pro-inflammatory cytokines production and
      increasing the humoral response to different antigens. Here, we evaluated the
      effect of P. acnes on a specific antitumor immune response elicited by a hybrid
      vaccine in a mouse melanoma model. Hybrid vaccine associated with P. acnes
      increased the absolute number of memory T cells, the IFN-gamma secretion by these
      cells and the IgG-specific titers to B16F10 antigens, polarizing the immune
      response to a T helper 1 pattern. Furthermore, the addition of P. acnes to a
      hybrid vaccine increased the cytotoxic activity of splenocytes toward B16F10 in
      vitro and avoided late tumor progression in a pulmonary colonization model. These
      results revealed the adjuvant effect of a killed P. acnes suspension, as it
      improved specific humoral and cellular immune responses elicited by DC-tumor cell
      hybrid vaccines.

PMID- 30300367
TI  - The effect of 3-month finasteride challenge on biomarkers for predicting cancer
      outcome on biopsy: Results of a randomized trial.
AB  - BACKGROUND: Finasteride, a 5-alpha reductase inhibitor may have effects on
      biomarkers such as prostate-specific antigen (PSA) that could be leveraged to
      improve screening. OBJECTIVE: To determine the predictive characteristics of
      biomarkers for prostate cancer for cancer on biopsy following 3 months of
      finasteride use compared with placebo. DESIGN, SETTING AND PARTICIPANTS: 383 men
      from multiple clinical sites with intermediate prostate cancer risk, without
      history of prostate cancer, were randomly allocated in a double-blinded manner,
      4:1, to receive either finasteride or placebo for 90 days at which time a
      prostate biopsy was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The
      primary outcomes were associations of biomarkers with prostate cancer that were
      tested using multiple logistic regression and area under the receiver operating
      curves (AUC). Biomarkers for PCA risk (PCA3, TMPRSS2:ERG (T2:ERG) gene product,
      and PSA) were measured at baseline and at biopsy in a blinded fashion to assess
      the predictive performance of baseline levels, 90-day levels, and measures of
      change relative to standard predictors. RESULTS AND LIMITATIONS: A total of 292
      (233 finasteride; 59 placebo) randomized patients underwent biopsy and were
      analyzed. On finasteride, baseline and 90-day measures of PCA3 and T2:ERG had
      similar moderate discrimination capacity with AUCs 62 to 65% (p-values < 0.001
      and 0.001, respectively), but their rates of change had no discrimination ability
      (AUC 51%, (95% CI 43 to 60% p = 0.72) and 48% (95% CI 44 to 60%, p = 0.62),
      respectively).) Relative to baseline, the 90-day PCA3 and PSA decreased in the
      finasteride group by 25% and 50%, respectively (both p<0.001). T2:ERG had a
      smaller, non-significant change post finasteride treatment (p = 0.08).
      CONCLUSIONS: Short-term finasteride therapy did not improve performance of the
      most commonly-employed prostate cancer biomarkers. Threshold values for new
      biomarkers of prostate cancer should be interpreted with caution in patients
      receiving finasteride until formal validation of test performance in these
      patients is conducted. PATIENT SUMMARY: Three months of finasteride treatment did
      not increase the accuracy for predicting the outcome on prostate biopsy but did
      have a significant effect on biomarker values. Adjustments to thresholds for
      biopsy for men on finasteride are proposed. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT01296672.

PMID- 30300368
TI  - The crowding-out effect of tobacco expenditure on household spending patterns in
      Bangladesh.
AB  - BACKGROUND: Tobacco consumption constitutes a sizable portion of household
      consumption expenditure, which can lead to reduced expenditures on other basic
      commodities. This is known as the crowding-out effect. This study analyzes the
      crowding-out effect of tobacco consumption in Bangladesh, and the research
      findings have relevance for strengthening the tobacco control for improving
      health and well-being. METHODS: We analyzed data from the Bangladesh Household
      Income and Expenditure Survey 2010 to examine the differences in consumption
      expenditure pattern between tobacco user and non-user households. We further
      categorize tobacco user households in three mutually exclusive groups of smoking
      only, smokeless-only, and dual (both smoking and smokeless); and investigated the
      crowding-out effects for these subgroups. We compared the mean expenditure shares
      of different types of households, and then estimated the conditional Engel curves
      for various expenditure categories using Seemingly Unrelated Regression (SUR)
      method. Crowding-out was considered to have occurred if estimated coefficient of
      the tobacco use indicator was negative and statistically significant. RESULTS: We
      find that tobacco user households on average allocated less in clothing, housing,
      education, energy, and transportation and communication compared to tobacco non
      user households. The SUR estimates also confirmed crowding-out in these
      consumption categories. Mean expenditure share of food and medical expenditure of
      tobacco user households, however, are greater than those of tobacco non-user
      households. Albeit similar patterns observed for different tobacco user
      households, there were differences in magnitudes depending on the type of tobacco
      use, rural-urban locations and economic status. CONCLUSION: Policy measures that
      reduce tobacco use could reduce displacement of commodities by households with
      tobacco users, including those commodities that can contribute to human capital
      investments.

PMID- 30300369
TI  - Associations of lack of voluntary private insurance and out-of-pocket
      expenditures with health inequalities. Evidence from an international
      longitudinal survey in countries with universal health coverage.
AB  - OBJECTIVES: In countries with universal health coverage (UHC), national public
      health insurances cover 70% of health expenditures on average, but health care
      user fees and out-of-pocket expenditures have been neglected in empirical patient
      centered health inequality research. This study is the first to investigate how
      health care-related factors are associated with health status among middle-aged
      and elderly people-vulnerable groups for the burden of illness-in countries with
      UHC. DESIGN: Longitudinal observational cohort study. SETTING: Population-based
      cohort Survey of Health, Ageing and Retirement in Europe (SHARE) in twelve
      countries with UHC. PARTICIPANTS: Non-institutionalized people aged 50 and older
      (n = 29,260). Two subsamples were also used: participants without global activity
      limitation at baseline (n = 16,879) and participants without depression at
      baseline (n = 21,178). MAIN OUTCOME MEASURES: Risk of death, risk of global
      activity limitations, and risk of depression. We used mixed-effects Cox
      proportional hazards regressions to estimate hazard ratios (HR) for all-cause
      mortality, physical limitations, and depression. RESULTS: Having a voluntary
      private insurance to cover health expenses not included in the public health care
      system (44.1% of the total sample) was a protective factor for all outcomes
      (HR<=0.91), controlling for a large range of socio-economic variables. On the
      contrary, having out-of-pocket expenditures (62.4%) was a risk factor (HR>=1.12).
      CONCLUSIONS: UHC systems are not free from health inequalities: there is a
      potential effect of lack of voluntary private insurance and out-of-pocket
      expenditures on mortality and health. Health care-related factors should be at
      focus in future researches designed to understand and address health
      inequalities. Reducing out-of-pocket expenditures and developing voluntary
      private insurance may protect against premature illness and death.

PMID- 30300370
TI  - Enhancement of brackish water desalination using hybrid membrane distillation and
      reverse osmosis systems.
AB  - Desalination of geothermal brackish water by membrane distillation (MD) provides
      a low recovery rate, but integrating MD with reverse osmosis (RO) can maximize
      the production rate. In this study, different design configurations of a hybrid
      system involving brine recycling and cascading are studied via simulations, and
      the performance improvement due to the process integration is substantiated via
      the increased recovery rate and reduced specific energy consumption. Brine
      recycling is also found to improve the recovery rate considerably to 40% at an
      energy cost of 0.9 $/m3. However, this achievement is only valid when the final
      brine is recycled to the RO feed: when the final brine is recycled to the MD
      feed, the overall performance degrades because the recycled brine cools the feed
      and causes a serious reduction in the driving force and the consequent production
      rate. Configuring the hybrid system in multiple stages connected in series
      increases the recovery rate to 90% and reduces the specific energy consumption to
      0.9 MJ/kg. Although the specific energy cost increases dramatically because
      external inter-stage heating is implemented, using a free energy source (such as
      a geothermal or waste-energy source) for inter-stage heating could provide the
      optimum configuration.

PMID- 30300371
TI  - Effectiveness of a multifactorial intervention for dizziness in older people in
      primary care: A cluster randomised controlled trial.
AB  - OBJECTIVES: Dizziness is common in older people. Physicians are often unable to
      identify a specific cause for dizziness in older people, even after an extensive
      diagnostic work-up. A prognosis-oriented approach, i.e. treating modifiable risk
      factors for an unfavourable course of dizziness, may reduce dizziness-related
      impairment in older people in primary care. DESIGN: Cluster randomized controlled
      trial. SETTING: 45 primary care practices in The Netherlands. PARTICIPANTS: 168
      participants aged >=65y who consulted their general practitioner for dizziness
      and experienced significant dizziness-related impairment (Dizziness Handicap
      Inventory (DHI) >=30). Participants were part of to the intervention group (n =
      83) or control group (n = 85), depending on whether they were enlisted in an
      intervention practice or in a control practice. INTERVENTIONS: The multifactorial
      intervention consisted of: medication adjustment in case of >=3 prescribed fall
      risk-increasing drugs (FRIDs) and/or stepped mental health care in case of
      anxiety disorder and/or depression and/or exercise therapy in case of impaired
      functional mobility. The intervention was compared to usual care. OUTCOME
      MEASURES: The primary outcome was dizziness-related impairment. Secondary
      outcomes were quality of life (QoL), dizziness frequency, fall frequency, anxiety
      and depression, use of FRIDs. RESULTS: Intention-to-treat analysis showed no
      significant intervention effect on dizziness-related impairment (DHI score
      difference -0.69 [95% CI -5.66;4.28]; p = 0.79). The intervention proved
      effective in reducing the number of FRIDs (FRID difference -0.48 [95% CI -0.89;
      0.06]; p = 0.02). No significant intervention effects were found on other
      secondary outcomes. The uptake of and adherence to the interventions was
      significantly lower in patients eligible for >=2 interventions compared to
      patients eligible for one intervention (p<0.001). CONCLUSIONS: The multifactorial
      intervention for dizziness in older patients showed no significant intervention
      effect on most outcomes and adherence to the multifactorial intervention was low.
      Although multifactorial treatment for older dizzy people seems promising in
      theory, we question its feasibility in daily practice. Future research could
      focus on a sequential treatment for dizziness, e.g. measuring effectiveness of
      various evidence-based therapies in a stepwise approach.

PMID- 30300372
TI  - High variability phonetic training in adaptive adverse conditions is rapid,
      effective, and sustained.
AB  - This paper evaluates a novel high variability phonetic training paradigm that
      involves presenting spoken words in adverse conditions. The effectiveness,
      generalizability, and longevity of this high variability phonetic training in
      adverse conditions was evaluated using English phoneme contrasts in three
      experiments with Malaysian multilinguals. Adverse conditions were created by
      presenting spoken words against background multi-talker babble. In Experiment 1,
      the adverse condition level was set at a fixed level throughout the training and
      in Experiment 2 the adverse condition level was determined for each participant
      before training using an adaptive staircase procedure. To explore the
      effectiveness and sustainability of the training, phonemic discrimination ability
      was assessed before and immediately after training (Experiments 1 and 2) and 6
      months after training (Experiment 3). Generalization of training was evaluated
      within and across phonemic contrasts using trained and untrained stimuli. Results
      revealed significant perceptual improvements after just three 20-minute training
      sessions and these improvements were maintained after 6 months. The training
      benefits also generalized from trained to untrained stimuli. Crucially,
      perceptual improvements were significantly larger when the adverse conditions
      were adapted before each training session than when it was set at a fixed level.
      As the training improvements observed here are markedly larger than those
      reported in the literature, this indicates that the individualized phonetic
      training regime in adaptive adverse conditions (HVPT-AAC) is highly effective at
      improving speech perception.

PMID- 30300373
TI  - Estimating recent HIV incidence among young men who have sex with men:
      Reinvigorating, validating and implementing Osmond's algorithm for behavioral
      imputation.
AB  - HIV incidence information is essential for epidemic monitoring and evaluating
      preventive interventions. However, reliable HIV incidence data is difficult to
      obtain, especially among marginalized populations, such as young men who have sex
      with men (YMSM). Here we evaluate the reliability of an alternative HIV incidence
      assessment method, behavioral imputation, as compared to serologically estimated
      HIV incidence. Recent HIV incidence among YMSM (aged 18 to 21 and 18 to 24 years)
      enrolled in a cohort study in Bangkok from 2006 to 2014 was estimated using two
      mid-point methods for seroconversion: 1) between age of first anal intercourse
      and first HIV-positive test (without previous HIV-negative test) (behavioral
      imputation) and 2) between the date of last negative and first positive HIV test
      (serological estimation). Serologically estimated HIV incidence was taken as the
      "gold standard" to evaluate between-method agreement. At baseline, 314 YMSM age
      18 to 21 years accumulated 674 person-years (PY) of follow-up since first anal
      intercourse. Considering that 50 men had prevalent HIV infection, the
      behaviorally imputed HIV incidence was 7.4 per 100 PY. Of the remaining 264 HIV
      negative men, 54 seroconverted for HIV infection during the study, accumulating
      724 PY of follow-up and a serologically estimated HIV incidence of 7.5 per 100
      PY. At baseline, 712 YMSM age 18 to 24 years (including 18 to 21-year-old men
      analyzed above) accumulated 2143 PY of follow-up since first anal intercourse.
      Considering that 151 men had prevalent HIV infection, the behaviorally imputed
      HIV incidence was 7.0 per 100 PY. Of the remaining 561 HIV-negative men, 125
      seroconverted for HIV infection during the study, accumulating 1700 PY of follow
      up and a serologically estimated HIV incidence of 7.4 per 100 PY. Behavioral
      imputation and serological estimation are in good agreement when estimating
      recent HIV incidence in YMSM.

PMID- 30300374
TI  - Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents.
AB  - Recent studies have shown that HDAC inhibitors act synergistically with
      camptothecin derivatives in combination therapies. To exploit this synergy, new
      hybrid molecules targeting simultaneously topoisomerase I and HDAC were designed.
      In particular, a selected multivalent agent containing a camptothecin and a SAHA
      like template showed a broad spectrum of antiproliferative activity, with IC50
      values in the nanomolar range. Preliminary in vivo results indicated a strong
      antitumor activity on human mesothelioma primary cell line MM473 orthotopically
      xenografted in CD-1 nude mice and very high tolerability.

PMID- 30300376
TI  - HCF-CRS: A Hybrid Content based Fuzzy Conformal Recommender System for providing
      recommendations with confidence.
AB  - A Recommender System (RS) is an intelligent system that assists users in finding
      the items of their interest (e.g. books, movies, music) by preventing them to go
      through huge piles of data available online. In an effort to overcome the data
      sparsity issue in recommender systems, this research incorporates a content based
      filtering technique with fuzzy inference system and a conformal prediction
      approach introducing a new framework called Hybrid Content based Fuzzy Conformal
      Recommender System (HCF-CRS). The proposed framework is implemented to be used in
      the domain of movies and it provides quality recommendations to users with a
      confidence level and an improved accuracy. In our proposed framework, first, a
      Content Based Filtering (CBF) technique is applied to create a user profile by
      considering the history of each user. CBF is useful in the situations like: lack
      of demographic information and the data sparsity problems. Second, a Fuzzy based
      technique is incorporated to find the similarities and differences between the
      user profile and the movies in the dataset using a set of fuzzy rules to get a
      predicted rating for each movie. Third, a Conformal prediction algorithm is
      implemented to calculate the non-conformity measure between the predicted ratings
      produced by fuzzy system and the actual ratings from the dataset. A p-value
      (confidence measure) is computed to give a level of confidence to each
      recommended item and a bound is set on the confidence level called a significance
      level epsilon, according to which the movies only above the specified
      significance level are recommended to user. By building a confidence centric
      hybrid conformal recommender system using the content based filtering approach
      with fuzzy logic and conformal prediction algorithm, the reliability and the
      accuracy of the system is considerably enhanced. The experiments are evaluated on
      MovieLens and Movie Tweetings datasets for recommending movies to the users and
      they are compared with other state-of-the-art recommender systems. Finally, the
      results confirm that the proposed algorithms perform better than the traditional
      ones.

PMID- 30300375
TI  - High prevalence of spa type t571 among methicillin-susceptible Staphylococcus
      aureus from bacteremic patients in a French University Hospital.
AB  - Staphylococcus aureus bacteremia is one of the most frequent severe bacterial
      infections worldwide, with an associated mortality of about 20-40% in developed
      countries. In 2013, we noted an increase in this infection in the teaching
      hospital in Grenoble, France, compared to 2012. The mean incidence of S. aureus
      bacteremia was 0.28 per 1,000 patient-days in 2012 and 0.35 per 1,000 patient
      days in 2013. This trend was confirmed in 2014 (0.35 per 1,000 patient-days). In
      the present work we aimed to study the population of patients presenting with S.
      aureus bacteremia in 2013 and to genotype the corresponding S. aureus strains in
      order to identify a successful and/or virulent genotype to design a specific
      infection control program. One hundred ninety-one S. aureus isolates (including 9
      methicillin-resistant) out of 199 corresponding cases of bacteremia were
      characterized with the spa typing method. Among 108 spa types, t571, t002, t008
      and t084 were the most prevalent. Although not widely prevalent, t571 was the
      most frequently identified clone (8.4% of all isolates). Spa type t571 has been
      described in previous studies as belonging to the clonal complex CC398, which is
      consistent with the recent emergence of methicillin-susceptible S. aureus CC398
      reported in blood cultures in Europe.

PMID- 30300377
TI  - Surgical resection for rectal cancer. Is laparoscopic surgery as successful as
      open approach? A systematic review with meta-analysis.
AB  - BACKGROUND: Recently, it has been questioned if minimally invasive surgery for
      rectal cancer was surgically successful. We decided to perform a meta-analysis to
      determine if minimally invasive surgery is adequate to obtain a complete
      resection for curable rectal cancer. METHODS: A systematic search pertaining to
      evaluation between laparoscopic and open rectal resection for rectal cancer was
      performed until 30th November 2016 in the electronic databases (PubMed, Web of
      Science, Scopus, EMBASE), using the following search terms in all possible
      combinations: rectal cancer, laparoscopy, minimally invasive and open surgery.
      Outcomes analyzed were number of clear Distal Resection Margins (DRM or DM),
      complete Circumferential Resection Margins (CRM) and complete, nearly complete
      and incomplete Total Mesorectal Excision (TME) and of patients who received
      laparoscopic or open treatment for rectal cancer. RESULTS: 12 articles were
      included in the final analysis. The prevalence of successful surgical resection
      was similar between open and laparoscopic surgery. About distance from distal
      margin of the specimen, clear CRM and complete TME there were no statistically
      significant difference between the two groups (MD = -0.090 cm, p = 0.364, 95% CI 
      0.283, 0.104; OR = 1.032, p = 0.821, 95% CI 0.784, 1.360; OR = 0.933, p = 0.720,
      95% CI 0.638, 1.364, respectively). The analysis of nearly complete TME showed a
      significant difference between the two groups (OR = 1.407, p = 0.006, 95% CI
      1.103, 1.795), while the analysis of incomplete TME showed a non-significant
      difference (OR = 1.010, p = 0.964, 95% CI 0.664, 1.534). CONCLUSIONS: By pooling
      together data from 5 RCTs and 7 nRCTs, we are able to provide evidence of safety
      and efficacy of minimally invasive surgery. Waiting for further randomized
      clinical trials, our results are encouraging to introduce laparoscopic rectal
      resection in daily practice.

PMID- 30300378
TI  - Influence of mirror therapy and motor imagery on intermanual transfer effects in
      upper-limb prosthesis training of healthy participants: A randomized pre-posttest
      study.
AB  - The effect that a motor skill trained on one side can lead to improvement in the
      untrained side is called intermanual transfer. Intermanual transfer can help
      enhance upper limb prosthetic training. To determine the influence of mirror
      therapy and motor imagery on intermanual transfer in upper limb prosthesis
      training, a pseudo-randomized clinical trial, single blinded, with a pre-posttest
      design was used. Forty-seven able-bodied, right-handed participants were pseudo
      randomly assigned to two training groups and one control group. One training
      group undertook an intermanual transfer training program, using an upper-limb
      prosthetic simulator with added mirror therapy and motor imagery. The second
      training group completed only the intermanual transfer training program. The
      control group completed a sham training: a dummy training without using the
      prosthesis simulator. The program lasted five consecutive days. To determine the
      improvement in skill, a test was administered before, immediately after, and six
      days after the training program. Training used the "unaffected" arm; tests were
      performed with the "affected" arm, resembling the amputated limb. Movement time,
      the time from the beginning of the movement until completion of the task; hand
      opening, the duration of the maximum prosthetic hand opening; and grip-force
      control, the deviation from the required force during a tracking task. No
      intermanual transfer effects were found: neither the intermanual transfer
      training program, nor the additional mirror therapy and motor imagery affected
      prosthesis skills. A limitation of the study was that the training program was
      applied to able-bodied subjects instead of patients with an amputation. Contrary
      to previous studies, no intermanual transfer effects were found. Additional
      mirror therapy and motor imagery did not ameliorate intermanual transfer effects.

PMID- 30300379
TI  - Child sexual abuse in India: A systematic review.
AB  - OBJECTIVE: Child Sexual Abuse (CSA) is a pressing human right issue and public
      health concern. We conducted a systematic review of quantitative and qualitative
      studies published in the past decade on CSA in India to examine the distribution
      of the prevalence estimates for both genders, to improve understanding of the
      determinants and consequences of CSA and identify gaps in the current state of
      research. METHODS: For this systematic review, we searched electronic literature
      databases (PubMed, POPLINE, and PsycINFO) for articles published in English on
      Child Sexual Abuse in India between January 1, 2006 and January 1, 2016 using 55
      search terms. Data were extracted from published articles only. FINDINGS: Fifty
      one studies met inclusion criteria for the review. The review indicates that
      prevalence rates of CSA is high among both boys and girls in India. Due to
      heterogeneity of study designs and lack of standardised assessments, reported
      prevalence estimates varied greatly among both genders in different studies.
      There is a need to conduct representative studies using a validated instrument to
      obtain valid epidemiological estimates. Commercial sex workers, men who have sex
      with men, and women with psychiatric disorders were at higher risks for sexual
      abuse during childhood. In addition, the synthesis of qualitative data across
      studies included in the review suggests that exposure and perpetration of CSA is
      a multifaceted phenomenon grounded in the interplay between individual, family,
      community, and societal factors. The review indicates poor physical, behavioural,
      social, and mental health outcomes of CSA in India. We conclude with a research
      agenda calling for quantitative and qualitative studies to explore the
      determinants and perpetration of child sexual abuse in India from an ecological
      lens. This research agenda may be necessary to inform the development of a
      culturally tailored primary prevention and treatment strategy for CSA victims in
      India.

PMID- 30300380
TI  - Maternal dissatisfaction with their children's body size in private schools in
      the Federal District, Brazil.
AB  - We investigated the prevalence of maternal dissatisfaction with their child's
      body size and its associated factors among mothers of first- to third-grade
      elementary school students in private schools in the Federal District, Brazil.
      This is a cross-sectional study with 548 mother-schoolchildren pairs. We measured
      children's weight and height, and collected their mother's sociodemographic data
      and Body Mass Index using an online questionnaire. We also verified maternal body
      dissatisfaction and maternal dissatisfaction with their child's body size using
      Shape Scales. Most mothers (50.5%) were dissatisfied with their child's body
      size. Mothers of boys (Adjusted OR = 2.85) were more likely to want a larger
      silhouette for their child, while mothers of girls (Adjusted OR = 3.18),
      overweight (Adjusted OR = 24.83) and obese (Adjusted OR = 189.86) children were
      more likely to want a thinner silhouette for their child. A positive correlation
      was observed between maternal dissatisfaction with their own body and maternal
      dissatisfaction with their children's body size (rs = 0.178). There was a high
      prevalence of maternal dissatisfaction with their child's body size, particularly
      among mothers of overweight and obese children. Additional studies should be
      conducted to better understand the influence of this dissatisfaction on maternal
      practices and attitudes related to their child's body, food consumption, and
      lifestyle.

PMID- 30300381
TI  - An integrative approach using real-world data to identify alternative therapeutic
      uses of existing drugs.
AB  - Different computational approaches are employed to efficiently identify novel
      repositioning possibilities utilizing different sources of information and
      algorithms. It is critical to propose high-valued candidate-repositioning
      possibilities before conducting lengthy in vivo validation studies that consume
      significant resources. Here we report a novel multi-methodological approach to
      identify opportunities for drug repositioning. We performed analyses of real
      world data (RWD) acquired from the United States Food and Drug Administration's
      Adverse Event Reporting System (FAERS) and the claims database maintained by the
      Japan Medical Data Center (JMDC). These analyses were followed by cross
      validation through bioinformatics analyses of gene expression data. Inverse
      associations revealed using disproportionality analysis (DPA) and sequence
      symmetry analysis (SSA) were used to detect potential drug-repositioning signals.
      To evaluate the validity of the approach, we conducted a feasibility study to
      identify marketed drugs with the potential for treating inflammatory bowel
      disease (IBD). Primary analyses of the FAERS and JMDC claims databases identified
      psycholeptics such as haloperidol, diazepam, and hydroxyzine as candidates that
      may improve the treatment of IBD. To further investigate the mechanistic
      relevance between hit compounds and disease pathology, we conducted
      bioinformatics analyses of the associations of the gene expression profiles of
      these compounds with disease. We identified common biological features among
      genes differentially expressed with or without compound treatment as well as
      disease-perturbation data available from open sources, which strengthened the
      mechanistic rationale of our initial findings. We further identified pathways
      such as cytokine signaling that are influenced by these drugs. These pathways are
      relevant to pathologies and can serve as alternative targets of therapy.
      Integrative analysis of RWD such as those available from adverse-event databases,
      claims databases, and transcriptome analyses represent an effective approach that
      adds value to efficiently identifying potential novel therapeutic opportunities.

PMID- 30300383
TI  - Early hematoma retraction in intracerebral hemorrhage is uncommon and does not
      predict outcome.
AB  - BACKGROUND: Clot retraction in intracerebral hemorrhage (ICH) has been described
      and postulated to be related to effective hemostasis and perihematoma edema (PHE)
      formation. The incidence and quantitative extent of hematoma retraction (HR) is
      unknown. Our aim was to determine the incidence of HR between baseline and time
      of admission. We also tested the hypothesis that patients with HR had higher PHE
      volume and good prognosis. METHODS: This was a retrospective single-centre study
      in which serial planimetric volume measurements of the total hematoma volume
      (parenchymal (IPH) and intraventricular (IVH)) and PHE were performed in ICH
      patients with baseline non-contrast computed tomography (CT) completed within 6
      hours of onset and follow-up CT 24 (+/-12) hours from symptom onset. HR was
      defined as a decrease in volume of >3ml or >15%, and hematoma expansion (HE) as
      an increase of >6ml or >30%. All other patients were categorized as stable
      hematoma (HS). Good outcome was defined as modified Rankin Scale (mRS) 0-2 at 90
      days. RESULTS: A total of 136 patients (mean age = 69.3+/-13.39 years, 58.1%
      male) were included. Median (interquartile range) baseline total hematoma volume
      was 14.96 (7.80, 31.88) ml. HR >3ml and >15% occurred in 6 (4.4%) and 8 (5.9%)
      patients, respectively. Neither definition of HR was associated with follow-up
      PHE (p>0.297) or good outcome (p>0.249). IVH was the only independent predictor
      of HR (p<0.0241). CONCLUSIONS: Early HR is rare and associated with IVH, but not
      with PHE or clinical outcome. There was no relationship between HR, PHE, and
      patient prognosis. Therefore, HR is unlikely to be a useful endpoint in clinical
      ICH studies.

PMID- 30300382
TI  - Carious status and supragingival plaque microbiota in hemodialysis patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the carious status and the
      microbial profiles of supragingival plaque in patients with chronic kidney
      disease undergoing hemodialysis. METHODS: This study included 30 patients with
      chronic kidney disease undergoing hemodialysis as well as 30 control subjects.
      Dental examination was performed and the decayed-missing-filled-teeth was
      recorded. Supragingival plaque was taken and analyzed using 16S rRNA gene
      amplicon by Illumina MiSeq sequencing to detect microbial composition and
      community diversity and structure. RESULTS: The level of decayed-missing-filled
      teeth was higher in the hemodialysis group than that in the control group.
      Microbial analysis showed a decrease in alpha diversity and a increase in
      relative abundance and prevalence of many acidogenic and aciduric caries related
      species in the supragingival plaque samples of the hemodialysis patients,
      including Streptococcus mutans, Lactobacillus salivarius, Lactobacillus
      fermentum, Lactobacillus vaginalis, Scardovia wiggsiae F0424, and Actinomyces
      naeslundii. CONCLUSION: Our results suggested that the hemodialysis patients were
      more susceptible to caries. More attentions for caries prevention and treatment
      should be paid to improve their life quality, and even to reduce their
      cardiovascular events and survival.

PMID- 30300384
TI  - Bat rabies in Washington State: Temporal-spatial trends and risk factors for
      zoonotic transmission (2000-2017).
AB  - BACKGROUND: Rabies is a zoonotic viral disease that can affect all mammals. In
      the United States, the majority of human rabies cases are caused by bats, which
      are the only known reservoirs for rabies virus (RABV) in Washington State. We
      sought to characterize bat RABV epidemiology in Washington among bats submitted
      by the public for RABV testing. METHODS: We examined temporal and spatial trends
      in RABV positivity (% positive) for taxonomically identified bats submitted to
      diagnostic laboratories during 2006-2017. For a subset of Myotis species, we
      evaluated sensitivity and predictive value positive (PPV) of morphological
      identification keys, using mitochondrial markers (cytochrome b) as a reference.
      For bats tested during 2000-2016, we analyzed RABV positivity by circumstances of
      encounters with humans, cats, and dogs. RESULTS: During 2006-2017, RABV
      positivity for all bat species was 6.0% (176/2,928). Among species with >=100
      submissions, RABV positivity was 2.0%-11.7% and highest among big brown bats
      (Eptesicus fuscus). An increasing trend in annual positivity was significant only
      for big brown bats (P = 0.02), and was circumstantially linked to a geographic
      cluster. Sensitivity and PPV of morphological identification keys was high for M.
      evotis but varied for M. lucifugus, M. californicus, M. yumanensis, and M.
      septentrionalis. A positive RABV result was significantly associated with
      nonsynanthropic species, abnormal behavior, abnormal hiding, injury, biting,
      found in a body of water, found alive, found outdoors, and caught by a dog.
      CONCLUSION: Monitoring passive RABV surveillance trends enables public health
      authorities to perform more accurate risk assessments. Differences in temporal
      and spatial trends in RABV positivity by bat species indicate the importance of
      collecting taxonomic data, although morphological identification can be
      unreliable for certain Myotis species. Current public health practices for RABV
      exposures should be maintained as RABV infection in bats can never be excluded
      without diagnostic testing.

PMID- 30300385
TI  - A type 2 diabetes disease module with a high collective influence for Cdk2 and
      PTPLAD1 is localized in endosomes.
AB  - Despite the identification of many susceptibility genes our knowledge of the
      underlying mechanisms responsible for complex disease remains limited. Here, we
      identified a type 2 diabetes disease module in endosomes, and validate it for
      functional relevance on selected nodes. Using hepatic Golgi/endosomes fractions,
      we established a proteome of insulin receptor-containing endosomes that allowed
      the study of physical protein interaction networks on a type 2 diabetes
      background. The resulting collated network is formed by 313 nodes and 1147 edges
      with a topology organized around a few major hubs with Cdk2 displaying the
      highest collective influence. Overall, 88% of the nodes are associated with the
      type 2 diabetes genetic risk, including 101 new candidates. The Type 2 diabetes
      module is enriched with cytoskeleton and luminal acidification-dependent
      processes that are shared with secretion-related mechanisms. We identified new
      signaling pathways driven by Cdk2 and PTPLAD1 whose expression affects the
      association of the insulin receptor with TUBA, TUBB, the actin component ACTB and
      the endosomal sorting markers Rab5c and Rab11a. Therefore, the interactome of
      internalized insulin receptors reveals the presence of a type 2 diabetes disease
      module enriched in new layers of feedback loops required for insulin signaling,
      clearance and islet biology.

PMID- 30300386
TI  - Ablation of nasal-associated lymphoid tissue does not affect focal ischemic brain
      injury in mice.
AB  - Stroke is a devastating disease with a strong inflammatory component. It has been
      shown that part of this response is mediated by IL17+ gammadeltaT cells.
      gammadeltaT cells constitute a lymphocyte population with innate features that
      mainly populates epithelial surfaces including skin, intestine, and airways. We
      have shown that in the context of stroke, T cells migrate from the small
      intestine to the meninges but whether they can migrate from other epithelial
      surfaces is still unknown. Because of its proximity, one possible source of
      stroke-associated IL17+ gammadeltaT cells could be the Nasal-Associated Lymphoid
      Tissue (NALT) from which T cells could migrate along olfactory nerve sheaths
      through the cribriform plate into the brain and/or meninges. In order to study
      the role of NALT as a source for immune cells and/or inflammatory mediators in
      the context of stroke, we analyzed the effect of NALT ablation on immune cell
      infiltration and infarct volume after stroke. Infarct volume analysis did not
      show any significant difference between sham and NALT-ablated animals. In
      addition, no significant differences were found in immune cell infiltration in
      the brain or meninges of stroke animals subjected to NALT or Sham-ablation
      surgery. In conclusion, NALT ablation does not affect ischemic brain damage or
      immune cell infiltration in the meninges or brain after stroke.

PMID- 30300388
TI  - African cassava whitefly, Bemisia tabaci, cassava colonization preferences and
      control implications.
AB  - Cassava is a staple food for people across sub-Saharan Africa. Over the last 20
      years, there has been an increased frequency of outbreaks and crop damage in this
      region caused by the cassava-adapted Bemisia tabaci putative species. Little is
      known about when and why B. tabaci adults move and colonize new cassava crops,
      especially in farming systems that contain a mixture of cultivar types and plant
      ages. Here, we assessed experimentally whether the age and variety of cassava
      affected the density of B. tabaci. We also tested whether the age and variety of
      the source cassava field affected the variety preference of B. tabaci when they
      colonized new cassava plants. We placed uninfested potted "sentinel" plants of
      three cassava varieties (Nam 130, Nase 14, and Njule Red) in source fields
      containing one of two varieties (Nam 130 or Nase 14) and one of three age classes
      (young, medium, or old). After two weeks, the numbers of nymphs on the sentinel
      plants were used as a measure of colonization. Molecular identification revealed
      that the B. tabaci species was sub-Saharan Africa 1 (SSA1). We found a positive
      correlation between the density of nymphs on sentinel plants and the density of
      adults in the source field. The density of nymphs on the sentinels was not
      significantly related to the age of the source field. Bemisia tabaci adults did
      not preferentially colonize the sentinel plant of the same variety as the source
      field. There was a significant interactive effect, however, between the source
      and sentinel variety that may indicate variability in colonization. We conclude
      that managing cassava source fields to reduce B. tabaci abundance will be more
      effective than manipulating nearby varieties. We also suggest that planting a
      "whitefly sink" variety is unlikely to reduce B. tabaci SSA1 populations unless
      fields are managed to reduce B. tabaci densities using other integrative
      approaches.

PMID- 30300387
TI  - Molecular characterization of feline astrovirus in domestic cats from Northeast
      China.
AB  - Feline astrovirus (FeAstV) which belonged to the genus Mamastrovirus was first
      identified in the feces of kittens with diarrhea in the USA in 1981 by electron
      microscopy, and had been reported in many countries. Presently, there are no any
      reports of the circulation of FeAstV in mainland China. We performed this study
      to investigate the apparent prevalence and genetic variability of FeAstV infected
      in cats in mainland China for the first time. We tested fecal samples of 105 cats
      with diarrhea and 92 asymptomatic cats in five cities in northeast China by RT
      PCR targeting RNA-dependent RNA polymerase (RdRp) gene of FeAstV, and analyzed
      sequences variability and phylogenetic evolution based on the complete capsid
      gene of FeAstV strains obtained from positive samples. The overall prevalence of
      FeAstV was 23.4% (46/197) of which 38 were tested in cats with diarrhea (36.2%,
      38/105) and 8 were in asymptomatic cats (8.7%, 8/92). Mixed infection with other
      enteroviruses including feline parvovirus (FPV), feline bocavirus (FBoV) and
      feline kobuvirus (FeKoV) was found in 38 FeAstV-positive samples. Phylogenetic
      analysis based on the complete capsid gene revealed all FeAstV strains were
      divided into two different groups with a 0.454+/-0.016 of mean amino acid genetic
      distance between two groups, suggesting that FeAstVs should be classified into
      two different genotype species. This study provided the first molecular evidence
      that FeAstV with considerable genetic diversity was circulating in northeast
      China, and analyzed genetic variability and classification of FeAstVs for the
      first time.

PMID- 30300389
TI  - Wound healing in wild male baboons: Estimating healing time from wound size.
AB  - Wound healing in animals is important to minimize the fitness costs of infection.
      Logically, a longer healing time is associated with higher risk of infection and
      higher energy loss. In wild mammals, wounds caused by aggressive intraspecific
      interactions can potentially have lethal repercussions. Clarifying wounding rate
      and healing time is therefore important for measuring the severity of the
      attacks. In addition, impact of secondary damage of wounds (e.g., accidental
      peeling off of scabs) on heeling time is unknown despite the risk of infection in
      wild mammals. In baboons, most male injuries have been reported to result from
      male to male fights. Here, we investigated the relationship between wound size
      and healing time in wild anubis baboons to clarify the healing cost of physical
      attacks including secondary damage of wounds. Observations were conducted daily
      between August 2016 and July 2017 in Kenya for seven adult male anubis baboons.
      The individual wound rate was one per month on average. In 16 cases, we were able
      to assess the number of days required for wound healing, and the median healing
      time was 13 d. Wound healing time was longer for larger wounds. When the scab was
      peeled off accidentally because of external factors, healing time became longer.
      One of the causes of scabs' peeling off was baboons' scab-picking behavior, and
      the behaviour was considered self-injurious behavior. However, its predicted
      healing cost might not be high. We concluded that wounds less than 800 mm2 (the
      largest observed in this study) in baboon males have little effect on survival.
      Our results suggest that lethal wounds by physical attacks rarely occur in male
      baboons, and that healing time and delay caused by secondary damages can be
      estimated by measuring wound area.

PMID- 30300390
TI  - Glyphosate affects the larval development of honey bees depending on the
      susceptibility of colonies.
AB  - As the main agricultural insect pollinator, the honey bee (Apis mellifera) is
      exposed to a number of agrochemicals, including glyphosate (GLY), the most widely
      used herbicide. Actually, GLY has been detected in honey and bee pollen baskets.
      However, its impact on the honey bee brood is poorly explored. Therefore, we
      assessed the effects of GLY on larval development under chronic exposure during
      in vitro rearing. Even though this procedure does not account for social
      compensatory mechanisms such as brood care by adult workers, it allows us to
      control the herbicide dose, homogenize nutrition and minimize environmental
      stress. Our results show that brood fed with food containing GLY traces (1.25-5.0
      mg per litre of food) had a higher proportion of larvae with delayed moulting and
      reduced weight. Our assessment also indicates a non-monotonic dose-response and
      variability in the effects among colonies. Differences in genetic diversity could
      explain the variation in susceptibility to GLY. Accordingly, the transcription of
      immune/detoxifying genes in the guts of larvae exposed to GLY was variably
      regulated among the colonies studied. Consequently, under laboratory conditions,
      the response of honey bees to GLY indicates that it is a stressor that affects
      larval development depending on individual and colony susceptibility.

PMID- 30300392
TI  - Rates and predictors of recurrent work disability due to common mental health
      disorders in the United States.
AB  - CONTEXT: Despite the high prevalence of work disability due to common mental
      disorders (CMD), no information exists on the rates and predictors of recurrence
      in a United States population. OBJECTIVE: To estimate recurrent work disability
      statistics and evaluate factors associated with recurrence due to CMDs including
      adjustment, anxiety, bipolar, and depressive disorders. METHODS: Recurrent work
      disability statistics were calculated using a nationwide database of disability
      claims. For the CMDs, univariate and multiple variable analyses were used to
      examine demographic factors and comorbidities associated with the time to
      recurrence. RESULTS: Of the CMDs, cases with bipolar (n = 3,017) and depressive
      disorders (n = 20,058) had the highest recurrence densities, 98.7 and 70.9 per
      1000 person-years, respectively. These rates were more than three times higher
      than recurrence rates for other chronic disorders (e.g., diabetes, asthma; n =
      105,558) and non-chronic disorders (e.g., injury, acute illnesses; n = 153,786).
      Individuals with CMD were also more likely to have a subsequent disability
      distinct from their mental health condition. Risk factors for recurrent CMD
      disability included being younger, being an hourly employee, living in a
      geographic area with more college graduates, having more previous psychiatric
      visits, having a previous work leave, and the type of work industry. CONCLUSIONS:
      Results indicate that CMD patients may benefit from additional care and
      disability management both during and after their work absence to help prevent
      subsequent CMD and non-CMD related leaves.

PMID- 30300391
TI  - Effect of flow on targeting and penetration of angiopep-decorated nanoparticles
      in a microfluidic model blood-brain barrier.
AB  - The blood-brain barrier (BBB) limits transport of nanoparticles from the
      circulation to the brain parenchyma. Angiopep-2, a peptide which functions as a
      brain transport vector, can be coupled to nanoparticles in order to facilitate
      binding and internalization by brain endothelial cells (ECs), and subsequent BBB
      penetration. This multi-step process may be affected by blood flow over brain
      ECs, as flow influences endothelial cell phenotype as well as interactions of
      nanoparticles with ECs. In the present study a microfluidic BBB model was
      constructed to evaluate binding and internalization by brain ECs, as well as BBB
      penetration of Angiopep-2 coupled liposomes (Ang2-Liposomes) in static and flow
      conditions. Ang2 conjugation to liposomes markedly improved binding relative to
      unconjugated liposomes. Ang2-Liposomes bound and were internalized efficiently by
      brain endothelial cells after static incubation or with 1 dyne/cm2 of fluid shear
      stress (FSS), while binding was reduced at a FSS of 6 dyne/cm2. Penetration of
      the model microfluidic BBB by Ang2-Liposomes was higher at a FSS of 1 dyne/cm2
      and 6 dyne/cm2 than with static incubation. Analysis of barrier function and
      control experiments for receptor-mediated penetration provided insight into the
      magnitude of transcellular versus paracellular transport at each tested FSS.
      Overall, the results demonstrate that flow impacted the binding and BBB
      penetration of Ang2-functionalized nanoparticles. This highlights the relevance
      of the local flow environment for in vitro modeling of the performance of
      nanoparticles functionalized with BBB penetrating ligands.

PMID- 30300393
TI  - Quantitative optical coherence tomography angiography biomarkers for neovascular
      age-related macular degeneration in remission.
AB  - PURPOSE: To characterize quantitative optical coherence tomography angiography
      (OCT-A) parameters in active neovascular age-related macular degeneration (nAMD)
      patients under treatment and remission nAMD patients. DESIGN: Retrospective,
      cross-sectional study. PARTICIPANTS: One hundred and four patients of whom 72
      were in Group 1 (active nAMD) and 32 in Group 2 (remission nAMD) based on SD-OCT
      (Spectral Domain OCT) qualitative morphology. METHODS: This study was conducted
      at the Centre Ophtalmologique de l'Odeon between June 2016 and December 2017.
      Eyes were analyzed using SD-OCT and high-speed (100 000 A-scans/second) 1050-nm
      wavelength swept-source OCT-A. Speckle noise removal and choroidal
      neovascularization (CNV) blood flow delineation were automatically performed.
      Quantitative parameters analyzed included blood flow area (Area), vessel density,
      fractal dimension (FD) and lacunarity. OCT-A image algorithms and graphical user
      interfaces were built as a unified tool in Matlab coding language. Generalized
      Additive Models were used to study the association between OCT-A parameters and
      nAMD remission on structural OCT. The models' performance was assessed by the
      Akaike Information Criterion (AIC), Brier Score and by the area under the
      receiver operating characteristic curve (AUC). A p value of <= 0.05 was
      considered as statistically significant. RESULTS: Area, vessel density and FD
      were different (p<0.001) in the two groups. Regarding the association with CNV
      activity, Area alone had the highest AUC (AUC = 0.85; 95%CI: 0.77-0.93) followed
      by FD (AUC = 0.80; 95%CI: 0.71-0.88). Again, Area obtained the best values
      followed by FD in the AIC and Brier Score evaluations. The multivariate model
      that included both these variables attained the best performance considering all
      assessment criteria. CONCLUSIONS: Blood flow characteristics on OCT-A may be
      associated with exudative signs on structural OCT. In the future, analyses of OCT
      A quantitative parameters could potentially help evaluate CNV activity status and
      to develop personalized treatment and follow-up cycles.

PMID- 30300394
TI  - Muscle regeneration is disrupted by cancer cachexia without loss of muscle stem
      cell potential.
AB  - Cancer cachexia is a severe, debilitating condition characterized by progressive
      body wasting associated with remarkable loss of skeletal muscle weight. It has
      been reported that cancer cachexia disturbs the regenerative ability of skeletal
      muscle, but the cellular mechanisms are still unknown. Here, we investigated the
      skeletal muscle regenerative process in mouse colon-26 (C26) tumor cell-bearing
      mice as a C26 cancer cachexia model. Although the proliferation and
      differentiation abilities of muscle stem cells derived from the C26 tumor cell
      bearing mice were sustained in vitro, the proliferation and differentiation were
      severely impaired in the cachexic mice. The numbers of both macrophages and
      mesenchymal progenitors, which are critical players in muscle regeneration, were
      reduced in the cancer cachexic mice, indicating that the skeletal muscle
      regeneration process was disrupted by cancer cachexia. Furthermore, the number of
      infiltrated neutrophils was also reduced in cancer cachexia mice 24 hours after
      muscle injury, and the expression of critical chemokines for muscle regeneration
      was reduced in cancer cachexia model mice compared to control mice. Collectively,
      although the ability to regeneration of MuSCs was retained, cancer cachexia
      disturbed skeletal muscle regenerative ability by inhibiting the orchestrated
      muscle regeneration processes.

PMID- 30300395
TI  - Impact of successful treatment with direct-acting antiviral agents on health
      related quality of life in chronic hepatitis C patients.
AB  - BACKGROUND: Direct-acting antivirals (DAA) have demonstrated high efficacy to
      achieve sustained virological response (SVR) in chronic hepatitis C patients. We
      aim to assess the change in health-related quality of life (HRQoL) among patients
      successfully treated, and to identify predictors of this variation. METHODS: In a
      prospective observational study, patients with chronic hepatitis C who started
      DAA therapy between May 2016 and April 2017 completed the EQ-5D-5L questionnaire
      at baseline and 12 weeks after the end of therapy before knowing the virological
      result. Analysis included all patients with SVR. RESULTS: Median baseline EQ-5D
      5L scores of the 206 enrolled patients were 0.857 utility and 70.0 visual
      analogue scale (VAS). Following SVR, a reduction occurred in the proportion of
      patients with mobility problems (35% vs 24%, p = 0.012), pain/discomfort (60% vs
      42%, p<0.001) and anxiety/depression (57% vs 44%, p = 0.012), with an increase in
      utility (+0.053, p<0.001) and VAS (+10, p<0.001). Score improvements were also
      observed in cirrhotic (+0.048 utility, p = 0.027; +15 VAS, p<0.001) and HIV co
      infected patients (+0.039 utility, p = 0.036; +5 VAS, p = 0.002). In multivariate
      analyses, middle age (45-64 years) and baseline anxiety/depression were
      associated to greater improvement in utility after SVR, and moderate-advanced
      liver fibrosis and cirrhosis to greater increase in VAS score. Low baseline
      values were associated to greater improvements in utility value and VAS score.
      CONCLUSIONS: The cure of chronic hepatitis C infection with DAA has a short term
      positive impact on HRQoL with improvement in mobility, pain/discomfort,
      anxiety/depression, utility value and VAS score. Patients with poor baseline
      HRQoL were the most beneficed.

PMID- 30300396
TI  - Malaria prevention practices and associated environmental risk factors in a rural
      community in Wakiso district, Uganda.
AB  - BACKGROUND: Besides use of insecticide-treated mosquito nets (ITNs) and indoor
      residual spraying (IRS), other complimentary measures including suitable housing
      structures, and environmental management that reduce breeding of malaria vectors,
      can be implemented at households to prevent the disease. However, most studies on
      malaria prevention have focused mainly on ITNs and IRS. The aim of this study was
      therefore to assess malaria prevention practices beyond ITNs and IRS, and
      associated environmental risk factors including housing structure in rural Wakiso
      district, Uganda. METHODS: A clustered cross-sectional survey was conducted among
      727 households in Wakiso district. Data were collected using an interviewer
      administered questionnaire and observational checklist. The questionnaire
      assessed participants' household practices on malaria prevention, whereas the
      checklist recorded environmental risk factors for malaria transmission, and
      structural condition of houses. Poisson regression modeling was used to identify
      factors associated with use of mosquito nets by households. RESULTS: Of the 727
      households, 471 (64.8%) owned at least one mosquito net. Use of mosquito nets by
      households was higher with increasing education level of participants-primary
      (aPR = 1.27 [95% CI: 1.00-1.60]), secondary (ordinary level) (aPR = 1.47 [95% CI:
      1.16-1.85]) and advanced level / tertiary (aPR = 1.55 [95% CI: 1.19-2.01]), and
      higher household income (aPR = 1.09 [95% CI: 1.00-1.20]). Additionally,
      participants who were not employed were less likely to have mosquito nets used in
      their households (aPR = 0.83 [95% CI: 0.70-0.98]). Houses that had undergone IRS
      in the previous 12 months were 42 (5.8%), while 220 (43.2%) households closed
      their windows before 6.00 pm. Environmental risk factors found at households
      included presence of vessels that could potentially hold water for mosquito
      breeding 414 (56.9%), and stagnant water in compounds 144 (19.8%). Several
      structural deficiencies on houses that could promote entry of mosquitoes were
      found such as lack of screening in ventilators 645 (94.7%), and external doors
      not fitting perfectly into walls hence potential for mosquito entry 305 (42.0%).
      CONCLUSION: There is need to increase coverage and utilisation of ITNs and IRS
      for malaria prevention in Wakiso district, Uganda. In addition, other malaria
      prevention strategies such as environmental management, and improving structural
      condition of houses are required to strengthen existing malaria prevention
      approaches.

PMID- 30300397
TI  - The adoption of hypertension reference framework: An investigation among primary
      care physicians of Hong Kong.
AB  - BACKGROUND: The Hong Kong Government released a Reference Framework (RF-HT) for
      Hypertension Care for Adults in Primary Care Settings since 2010. No studies have
      evaluated its adoption by primary care physicians (PCPs) since its release. AIM:
      We aimed to evaluate the level of PCPs' adoption of the RF-HT and the potential
      barriers of its use in family practice. DESIGN AND SETTING: A cross-sectional
      study was conducted by a self-administered validated survey among all PCPs in
      Hong Kong through various means. METHODS: We assessed the level of and factors
      associated with its adoption by multivariate logistic regression modelling.
      RESULT: A total of 3,857 invitation episodes were sent to 2,297 PCPs in 2014
      2015. We received 383 completed questionnaires. The average score of adoption was
      3.43 out of 4.00, and 47.5% of PCPs highly adopted RF-HT in their daily
      consultations. Male practitioners (adjusted odds ratio [aOR] = 0.524, 95% CI =
      0.290-0.948, p = 0.033) and PCPs of public sector (aOR = 0.524, 95% CI = 0.292
      0.940, p = 0.030) were significantly less likely to adopt the RF-HT. PCPs with
      higher training completion or being academic fellow are more likely to adopt RF
      HT than those who were "nil to basic training completion" (aOR = 0.479, 95% CI =
      0.269-0.853, p = 0.012) or "higher trainee" (aOR = 0.302, 95% CI = 0.093-0.979, p
      = 0.046). Three most-supported suggestions on RF-HT improvement were
      simplification of RF-HT, provision of pocket version and promoting in patients.
      CONCLUSION: Among PCP respondents, the adoption level of the RF-HT was high.
      These findings also highlighted some factors associated with its adoption that
      could inform targeted interventions for enhancing its use in clinical practice.

PMID- 30300398
TI  - Evaluation of antivirals against tick-borne encephalitis virus in organotypic
      brain slices of rat cerebellum.
AB  - Neurotropic tick borne encephalitis virus (TBEV) causes life-threatening disease,
      and accounts for most cases of tick-transmitted viral infections in Central and
      Eastern Europe and Russia. No specific treatment for TBEV infections exists, and
      vaccination is recommended for people at risk. So far, various nucleoside
      analogues have been investigated in vitro as potential candidates for treatment
      of TBEV infections. However, in vitro experiments with more complex cell culture
      systems, such as organotypic culture slices which model the sophisticated
      architecture of the target tissue are lacking. Using TBEV as a model, we
      investigated the suitability of rat organotypic cerebellum slices (OCS) to study
      the effectiveness of nucleoside analogues with a well-known anti-TBEV activity.
      In these OCS, 50 MUM of the nucleoside analogues 2'-C-methyladenosine (2'-CMA)
      and especially 7-deaza-2'-C-methyladenosine (7-deaza-2'-CMA) exhibited strong
      inhibitory effects on TBEV replication, reducing viral titers to an average of
      103-fold and TBEV RNA content 60-90-fold. In contrast, the influence of 2'-C
      methylcytidine (2'-CMC) on TBEV replication was very weak, reducing virus titers
      by 10-fold and TBEV RNA content by 3-fold. In agreement with other studies, there
      was no noticeable difference in TBEV titers between OCS treated with 50 MUM of
      Ribavirin and the DMSO treated controls. All tested nucleoside analogues
      exhibited excellent cytotoxicity profiles at concentrations of 50 MUM. Our
      findings in OCS were highly comparable to data obtained in cell line culture
      systems. Therefore, OCS represent an ideal in vitro approach to study antivirals
      against TBEV and possibly other neurotropic viruses.

PMID- 30300399
TI  - MicroRNA-146a is induced by inflammatory stimuli in airway epithelial cells and
      augments the anti-inflammatory effects of glucocorticoids.
AB  - BACKGROUND: MicroRNAs (miRNAs) are emerging as central regulators of
      inflammation, but their role in asthma and airway epithelial cells is not well
      studied. Glucocorticoids are the cornerstone of therapy in asthma and other
      inflammatory disease, yet their mechanisms of action are not completely
      elucidated, and it is not clear whether miRNAs modulate their effects. OBJECTIVE:
      We aimed to identify miRNAs that regulate cytokine and chemokine expression in
      airway epithelial cells and whether these miRNAs are subject to the effects of
      glucocorticoids. METHODS AND RESULTS: MicroRNAomic analyses of immortalized,
      normal human bronchial epithelial cells identified 7 miRNAs that were altered by
      inflammatory cytokine treatment and 22 that were regulated by glucocorticoids (n
      = 3 for each treatment condition). MiR-146a emerged as a central candidate, whose
      expression was induced by TNF-alpha and repressed by glucocorticoids. Its role as
      a candidate in asthmatic inflammation was supported by expression profiling in
      human asthmatics, which showed that plasma miR-146a expression was elevated in
      asthma and associated with measures related to worse asthma outcomes, including
      elevated blood eosinophil counts, higher asthma control questionnaire scores, and
      need for higher doses of inhaled glucocorticoids. However, transfection of miR
      146a in A549 cells treated with TNF-alpha +/- glucocorticoids produced an anti
      inflammatory effect and increased efficacy of glucocorticoids. CONCLUSIONS: We
      propose a model whereby miR-146a is induced by inflammatory conditions as a
      feedback mechanism to limit inflammation. Exogenous administration of miR-146a
      augmented the effects of glucocorticoids and could be a novel therapeutic
      strategy to enhance efficacy of these medications.

PMID- 30300400
TI  - Associations between diabetes mellitus and pulmonary hypertension in chronic
      respiratory disease patients.
AB  - BACKGROUND: Pulmonary hypertension (PH) is a common complication of chronic
      respiratory disease. Recent studies have reported diabetes mellitus (DM) to be a
      poor prognostic factor in patients with chronic respiratory disease, including
      chronic obstructive pulmonary disease or interstitial pneumoniae. However, the
      association between DM and PH in chronic respiratory disease remains unclear. In
      this study, we aimed to investigate whether DM is a predictor of PH in patients
      with chronic respiratory disease. METHODS: We prospectively analyzed 386 patients
      in our hospital with chronic respiratory disease. An echocardiographic pressure
      gradient between the right atrium and the right ventricle of >= 40 mmHg was
      defined as PH. We compared the clinical characteristics and impact of DM between
      chronic respiratory disease patients with and those without PH. RESULTS: Of the
      386 patients, 42 (10.9%) were diagnosed as having PH. The PH group had higher
      modified medical research council (mMRC) grade and complication rate of DM, but
      not hypertension and hyperlipidemia, when compared to the non-PH group.
      Multivariable logistic regression analysis revealed that mMRC scale (odds ratio
      1.702, 95% confidence interval, 1.297 to 2.232, P < 0.001) and presence of DM
      (odd ratio 2.935, 95% confidence interval, 1.505 to 5.725, P = 0.002) were
      associated with PH in chronic respiratory disease patients. CONCLUSION: DM is
      potentially associated with PH and is an independent factor for prediction of PH
      in patients with chronic respiratory disease.

PMID- 30300401
TI  - Association of tumour necrosis factor-alpha (TNF-alpha) gene polymorphisms (-308
      G>A and -238 G>A) and the risk of severe dengue: A meta-analysis and trial
      sequential analysis.
AB  - Individual studies have assessed the association between TNF-alpha-308G>A and TNF
      alpha-238 G>A polymorphisms and severity of dengue infection. However, the
      results are inconclusive and most studies had small sample sizes. The objective
      of this study was to summarize the evidence of association between TNF-alpha-308
      G>A and TNF-alpha-238 G>A and severity of dengue infection. This study follows
      the preferred reporting items for systematic reviews and meta- analyses of
      genetic association studies, recommended by PLOS One. We calculated pooled odds
      ratio and its 95% confidence interval (CI) to estimate the association between
      TNF-alpha-308 G>A or TNF-alpha-238 G>A and the risk of severe dengue infections.
      To determine the information size required for this meta-analysis study, a trial
      sequential analysis (TSA) was done. Eight studies (640 cases and 1275 controls),
      which assessed the association of TNF-alpha-308 G>A or TNF-alpha-238 G>A and the
      risk of DHF were included. Overall, we found no significant association between
      TNF-alpha-308 G>A and the DHF risk in the allelic model (OR, 0.91; 95% CI, 0.51
      1.63), the recessive model (OR,1.32;95%CI,0.73-2.37), the dominant model
      (OR,0.93;95%CI:0.59-1.47) or the additive model (OR,1.43,95;95%CI:0.79-2.59).
      There was also no significant association between TNF-alpha-238 G>A and DHF risk
      under the allele contrast model (OR:1.51;95%CI:0.88-2.58), the recessive model
      (OR,1.48,95% CI:0.33-6.58), the dominant model (OR,1.48;95%CI:0.56-3.92), or the
      additive model (OR:1.5;95%CI:0.34-6.69). On subgroup analysis, neither the Asian
      population nor the non-Asian population showed significant association between
      TNF-alpha-308 G>A/TNF-alpha-238 G>A and the DHF risk under any genetic models.
      Leave-one-out meta-analysis showed stability of the results. TSA plots suggested
      that the sample size in this meta-analysis study was below the required
      information size. The findings suggest an inclusive evidence of the association
      between TNF-alpha-308/ TNF-alpha-238 G>A and the risk of developing severe dengue
      infection. Large studies with evidence of Hardy-Weinberg equilibrium, assessing
      gene-gene interactions are recommended.

PMID- 30300402
TI  - Association of monocyte myeloperoxidase with incident cardiovascular disease: The
      Atherosclerosis Risk in Communities Study.
AB  - Myeloperoxidase (MPO) is a heme-containing peroxidase found in azurophilic
      granules of neutrophils and monocytes. Epidemiological studies have reported
      greater plasma MPO concentration to be associated with increased incidence of
      several cardiovascular diseases (CVD), but the association of intracellular
      monocyte MPO (mMPO) with CVD is unclear. The prospective population-based
      Atherosclerosis Risk in Communities (ARIC) cohort study measured mMPO using flow
      cytometry in 1,465 participants. The association of mMPO with incident
      cardiovascular disease (CVD, comprising incident coronary heart disease (CHD),
      heart failure, stroke, peripheral artery disease, and cardiovascular mortality)
      was examined over a median 9.6 years of follow-up (n = 290 CVD events). There was
      no statistically significant association between mMPO and all incident CVD events
      in either age, sex, and race-adjusted proportional hazards models (HR (95% CI)
      across tertiles of mMPO: 1, 1.09 (0.76, 1.57), and 0.78 (0.52, 1.15), P-trend =
      0.21) or adjusted for other major CVD risk factors (HR (95% CI): 1, 1.17 (0.81,
      1.69), and 0.87 (0.58, 1.29), P-trend = 0.50). There also was no association
      between mMPO tertiles and incident CHD, heart failure, or all-cause mortality,
      examined separately. In conclusion, intracellular monocyte myeloperoxidase was
      not associated with incident cardiovascular disease in this prospective
      population-based study.

PMID- 30300403
TI  - High rates of death and loss to follow-up by 12 months of rifampicin resistant TB
      treatment in South Africa.
AB  - INTRODUCTION: Treatment success rates of rifampicin resistant (RR)/multi-drug
      resistant (MDR) tuberculosis (TB) in South Africa range from 43-48%, falling
      short of the World Health Organization's target of >=75%. We present rates and
      assess predictors of attrition by 12 months on treatment. METHODS: Prospective
      observational cohort analysis of adults (>=18 years) initiating RR/MDR-TB
      treatment from 01 March 2013 to 30 September 2016. Attrition was defined as a
      combination of death and loss to follow-up (LTFU; treatment interruption >=2
      months) by 12 months on treatment. Predictors of attrition were identified using
      Cox Proportional Hazards models to estimate crude (HR) and adjusted hazard ratios
      (aHR) with corresponding 95% confidence intervals. RESULTS: By 12 months on
      treatment, 75/240 (31.3%) patients had either died (37/240; 15.4%) or been LTFU
      (38/240; 15.8%). Patients with moderate/severe anaemia (aHR: 2.10; 95% CI 1.00
      4.39), and those who were smear positive at baseline (aHR: 2.04; 95% CI 1.01
      4.12) were significantly more likely to die or be lost from care. CONCLUSION: At
      this outpatient DR-TB treatment site, there was a high rate of attrition halfway
      through the standard treatment course at 12 months of 31%. High rates of
      attrition by 12 months on treatment may continue during the second-half of
      therapy.

PMID- 30300404
TI  - Emotional responses to conspecific distress calls are modulated by affiliation in
      cockatiels (Nymphicus hollandicus).
AB  - Vocal communication is used across the animal kingdom to transfer information
      from emitters to receivers, such as size, sex, age, dominance status or even
      emotional states. The transmission of an emotional state from one individual to
      another is called "emotional contagion" and is classified as the first level of
      empathy. Emotional contagion is thought to be stronger between familiar
      individuals. While affiliation represents a stronger relation between individuals
      than mere familiarity, it remains understudied whether affiliation modulates
      emotional reactions as well. Using cockatiels (Nymphicus hollandicus), we played
      back three types of audio stimuli to individual birds: a partner's distress call
      (emitted when birds are caught or forcibly restrained), a non-partner's distress
      call, and a control sound (white noise). The calls were recorded from familiar
      birds with either low (non-partners) or high levels of affiliation (partners).
      The subjects' response was scored using four behavioural parameters: the time
      spent near the loudspeaker, the amount of movements, the number of calls emitted,
      and the position of the crest. Across all variables, birds were more attentive
      and active when confronted to distress calls compared to control sounds,
      particularly when the distress call was emitted from a partner rather than a non
      partner. These results raise the possibility that distress calls do not only
      function as a stimulus-triggering automatic reaction in cockatiels but also
      transmit emotions. Moreover, affiliation enhanced emotional reactions to
      conspecific distress calls. Our data provides first insights into the mechanisms
      of emotional contagion in parrots.

PMID- 30300406
TI  - BlasterJS: A novel interactive JavaScript visualisation component for BLAST
      alignment results.
AB  - BACKGROUND: The wide range of potential applications has made the Basic Local
      Alignment Search Tool (BLAST) a ubiquitous tool in the field of Molecular
      Biology. Within this context, it is increasingly appealing to embed BLAST
      services within larger Web applications. RESULTS: This work introduces BlasterJS
      viewer, a new JavaScript library for the lightweight development of Web-based
      applications supporting the visualisation of BLAST outputs. BlasterJS detaches
      from similar data viewers by focusing on the visual and interactive display of
      sequence similarity results and being completely independent of BLAST services.
      BlasterJS is compatible with the text outputs generated by the BLAST family of
      programs, namely BLASTp, BLASTn, BLASTx, tBLASTn, and tBLASTx, and works in all
      major Web browsers. Furthermore, BlasterJS is available through the EBI's BioJS
      registry 5, which extends its potential use to a wider scope of bioinformatics
      applications. CONCLUSIONS: BlasterJS is new Javascript library that enables easy
      and seamless integration of visual and interactive representations of BLAST
      outputs in Web-based applications supporting sequence similarity search.
      BlasterJS is free accessible at http://sing-group.org/blasterjs/.

PMID- 30300405
TI  - The long-term use of foot orthoses affects walking kinematics and kinetics of
      children with flexible flat feet: A randomized controlled trial.
AB  - BACKGROUND: Due to inconclusive evidence on the effects of foot orthoses
      treatment on lower limb kinematics and kinetics in children, studies are needed
      that particularly evaluate the long-term use of foot orthoses on lower limb
      alignment during walking. Thus, the main objective of this study was to evaluate
      the effects of long-term treatment with arch support foot orthoses versus a sham
      condition on lower extremity kinematics and kinetics during walking in children
      with flexible flat feet. METHODS: Thirty boys aged 8-12 years with flexible flat
      feet participated in this study. While the experimental group (n = 15) used
      medial arch support foot orthoses during everyday activities over a period of
      four months, the control group (n = 15) received flat 2-mm-thick insoles (i.e.,
      sham condition) for the same time period. Before and after the intervention
      period, walking kinematics and ground reaction forces were collected. RESULTS:
      Significant group by time interactions were observed during walking at preferred
      gait speed for maximum ankle eversion, maximum ankle internal rotation angle,
      minimum knee abduction angle, maximum knee abduction angle, maximum knee external
      rotation angle, maximum knee internal rotation angle, maximum hip extension
      angle, and maximum hip external rotation angle in favor of the foot orthoses
      group. In addition, statistically significant group by time interactions were
      detected for maximum posterior, and vertical ground reaction forces in favor of
      the foot orthoses group. CONCLUSIONS: The long-term use of arch support foot
      orthoses proved to be feasible and effective in boys with flexible flat feet to
      improve lower limb alignment during walking.

PMID- 30300407
TI  - Outcomes of endovascular treatment versus bypass surgery for critical limb
      ischemia in patients with thromboangiitis obliterans.
AB  - We aimed to compare the clinical outcomes between endovascular treatment and
      inframalleolar bypass surgery for critical limb ischemia (CLI) in patients with
      thromboangiitis obliterans (TAO) and to assess the role of bypass surgery in the
      era of innovative endovascular treatment. Between January 2007 and December 2017,
      a total of 33 consecutive patients with the diagnosis of TAO presenting with CLI
      who underwent endovascular treatment (endovascular group, n = 22) or bypass
      surgery to the pedal or plantar vessels (bypass group, n = 11) were included and
      analyzed retrospectively. The primary endpoint was defined as a major amputation
      of the index limb, and the secondary endpoint was defined as graft occlusion,
      regardless of the number of subsequent procedures. In the bypass group, six
      patients (55%) had undergone previous failed endovascular procedures and/or
      arterial bypass surgery to the index limb before inframalleolar bypass, and two
      patients (18%) received microvascular flap reconstruction after bypass surgery.
      During the median follow-up period of 32 months (range 1-115 months), there were
      no significant differences in primary and secondary endpoints between the two
      groups although the bypass group had a higher Rutherford class than the
      endovascular group. Kaplan-Meier survival analysis showed that there were similar
      limb salvage (P = 0.95) and graft patency rates (P = 0.39). In conclusion,
      endovascular treatment is a valid strategy leading to an acceptable limb salvage
      rate for TAO patients, and surgical bypass to distal target vessels could play a
      vital role in cases of previous failed endovascular treatment or extensive soft
      tissue loss of the foot.

PMID- 30300408
TI  - Sepsis is associated with reduced spontaneous neutrophil migration velocity in
      human adults.
AB  - Sepsis is a common and deadly complication among trauma and surgical patients.
      Neutrophils must mobilize to the site of infection to initiate an immediate
      immune response. To quantify the velocity of spontaneous migrating blood
      neutrophils, we utilized novel microfluidic approaches on whole blood samples
      from septic and healthy individuals. A prospective study at a level 1 trauma and
      tertiary care center was performed with peripheral blood samples collected at <12
      hours, 4 days, and/or 14 days relative to study initiation. Blood samples were
      also collected from healthy subjects. Ex vivo spontaneous neutrophil migration
      was measured on 2 MUl of whole blood using microfluidic devices and time-lapse
      imaging. For each sample, individual neutrophils were tracked to calculate mean
      instantaneous velocity. Forty blood samples were collected from 33 patients with
      sepsis, and 15 blood samples were collected from age- and gender-matched healthy,
      control subjects. Average age was 61 years for septic patients with a male
      predominance (67%). Overall, average spontaneous neutrophil migration velocity in
      septic samples was 16.9 MUm/min, significantly lower than controls samples at
      21.1 MUm/min (p = 0.0135). Neutrophil velocity was reduced the greatest at <12
      hours after sepsis (14.5 MUm/min). Regression analysis demonstrated a
      significant, positive correlation between neutrophil velocity and days after
      sepsis (p = 0.0059). There was no significant association between neutrophil
      velocity and age, gender, APACHE II score, SOFA score, sepsis severity, total
      white blood cell count, or percentage of neutrophils. Circulating levels of the
      cytokines IL-6, IL-8, IL-10, MCP-1, IP-10, and TNF were additionally measured
      using bead-based multiplex assay and found to peak at <12 hours and be
      significantly increased in patients with sepsis at all three time points (<12
      hours, 4 days, and 14 days after sepsis) compared to healthy subjects. In
      conclusion, these findings may demonstrate an impaired ability of neutrophils to
      respond to sites of infection during the proinflammatory phase of sepsis.

PMID- 30300409
TI  - A mathematical model for predicting the adult height of girls with idiopathic
      central precocious puberty: A European validation.
AB  - BACKGROUND: A previous single-center study established a mathematical model for
      predicting the adult height (AH) in girls with idiopathic central precocious
      puberty (CPP). OBJECTIVE: To perform internal and external validations by
      comparing the actual AH to the calculated AH established by this model and to
      update it. METHODS: The original formula, calculated AH (cm) = 2.21 (height at
      initial evaluation, SD) + 2.32 (target height, SD) - 1.83 (luteinizing
      hormone/follicle-stimulating hormone peaks ratio) + 159.68, was established in a
      sample of 134 girls (group 4) and was applied to additional girls with CPP seen
      in the same center (group 1, n = 35), in Germany (group 2, n = 43) and in the
      Netherlands (group 3, n = 72). This formula has been updated based on these
      extended data, and both versions are available at the following location:
      http://www.kamick.org/lemaire/med/girls-cpp15.html. RESULTS: Despite the
      differences among the 4 groups in terms of their characteristics at the initial
      evaluation and the percentages of patients treated with the gonadotropin
      releasing hormone analogue, they have similar calculated and actual AHs. The
      actual AHs are 162.2+/-7.0, 163.0+/-7.6, 162.4+/-7.7 and 162.1+/-5.6 cm in groups
      1 to 4, respectively. They are highly correlated with the AHs calculated by the
      formula established in the original group (group 4), with R at 0.84, 0.67 and
      0.69 in groups 1 to 3, respectively. When the actual AHs and the AHs predicted by
      the Bayley and Pinneau method are compared, the R is 0.76, 0.51 and 0.64 in
      groups 1 to 3, respectively. The absolute differences between actual AHs and the
      calculated AHs are greater than 1 SD (5.6 cm) in 15%, 35% and 28% of the patients
      in groups 1 to 3, respectively. CONCLUSION: This study validates and updates the
      previously established formula for predicting AH in girls with CPP. This updated
      formula can help clinicians to make treatment decisions.

PMID- 30300411
TI  - Antimicrobial treatment practices among Ugandan children with suspicion of
      central nervous system infection.
AB  - Acute central nervous system (CNS) infections in children in sub-Saharan Africa
      are often fatal. Potential contributors include late presentation, limited
      diagnostic capacity and inadequate treatment. A more nuanced understanding of
      treatment practices with a goal of optimizing such practices is critical to
      prevent avoidable case fatality. We describe empiric antimicrobial treatment,
      antibiotic resistance and treatment adequacy in a prospective cohort of 459
      children aged two months to 12 years hospitalised for suspected acute CNS
      infections in Mbarara, Uganda, from 2009 to 2012. Among these 459 children, 155
      had a laboratory-confirmed diagnosis of malaria (case-fatality rate [CFR] 14%),
      58 had bacterial infections (CFR 24%) and 6 children had mixed malaria and
      bacterial infections (CFR 17%). Overall case fatality was 18.1% (n = 83). Of 219
      children with laboratory-confirmed malaria and/or bacterial infections, 182
      (83.1%) received an adequate antimalarial and/or antibiotic on the day of
      admission and 211 (96.3%) within 48 hours of admission. The proportion of those
      receiving adequate treatment was similar among survivors and non-survivors. All
      bacterial isolates were sensitive to ceftriaxone except one Escherichia coli
      isolate with extended-spectrum beta-lactamase (ESBL). The observed high mortality
      was not a result of inadequate initial antimicrobial treatment at the hospital.
      The epidemiology of CNS infection in this setting justifies empirical use of a
      third-generation cephalosporin, however antibiotic resistance should be monitored
      closely.

PMID- 30300412
TI  - The current status and effects of emergency drug shortages in China: Perceptions
      of emergency department physicians.
AB  - OBJECTIVES: The shortage of emergency drugs in China is severe. This study aimed
      to characterize emergency drug shortages in China and to measure their effects.
      METHODS: An online questionnaire based on a literature review was sent to
      emergency department physicians in Chinese secondary and tertiary hospitals from
      November 2016 to February 2017. The survey asked physicians questions about their
      experiences with emergency drug shortages. RESULTS: In total, 236 physicians from
      29 provinces participated in the survey. According to their responses, 90.7% of
      the respondents experienced drug shortages during the last year. More than half
      of the physicians (65.7%) reported that drug shortages occurred at least once a
      month. Hospitals in the eastern and western regions of China had more emergency
      drugs in shortage than hospitals in central China, especially those with many
      inpatient beds (>=800). In addition, the shortage situation was more serious in
      secondary hospitals than in tertiary hospitals. More respondents agreed that
      original medicines, injections, essential medicines, medicines without
      alternative agents and cheap medicines were more susceptible to shortages than
      generics, oral medicines, nonessential medicines, medicines with alternative
      agents and expensive medicines, respectively. Most respondents thought that drug
      shortages always, often or sometimes affected patients [delayed therapy (62.6%),
      longer rescue and recovery times (58.9%) and higher costs (58.7%)] and physicians
      [inconvenience (81.0%), higher pressure (76.5%) and harm to patient-doctor
      relationships (72%)] and compromised hospital reputations (55.1%). CONCLUSIONS:
      The shortage of emergency drugs in China is serious, especially in secondary
      hospitals located in eastern and western China. Emergency drug shortages have
      significant effects on patients and physicians.

PMID- 30300410
TI  - Identification of gene expression predictors of occupational benzene exposure.
AB  - BACKGROUND: Previously, using microarrays and mRNA-Sequencing (mRNA-Seq) we found
      that occupational exposure to a range of benzene levels perturbed gene expression
      in peripheral blood mononuclear cells. OBJECTIVES: In the current study, we
      sought to identify gene expression biomarkers predictive of benzene exposure
      below 1 part per million (ppm), the occupational standard in the U.S. METHODS:
      First, we used the nCounter platform to validate altered expression of 30 genes
      in 33 unexposed controls and 57 subjects exposed to benzene (<1 to >=5 ppm).
      Second, we used SuperLearner (SL) to identify a minimal number of genes for which
      altered expression could predict <1 ppm benzene exposure, in 44 subjects with a
      mean air benzene level of 0.55+/-0.248 ppm (minimum 0.203ppm). RESULTS: nCounter
      and microarray expression levels were highly correlated (coefficients >0.7,
      p<0.05) for 26 microarray-selected genes. nCounter and mRNA-Seq levels were
      poorly correlated for 4 mRNA-Seq-selected genes. Using negative binomial
      regression with adjustment for covariates and multiple testing, we confirmed
      differential expression of 23 microarray-selected genes in the entire benzene
      exposed group, and 27 genes in the <1 ppm-exposed subgroup, compared with the
      control group. Using SL, we identified 3 pairs of genes that could predict <1 ppm
      benzene exposure with cross-validated AUC estimates >0.9 (p<0.0001) and were not
      predictive of other exposures (nickel, arsenic, smoking, stress). The predictive
      gene pairs are PRG2/CLEC5A, NFKBI/CLEC5A, and ACSL1/CLEC5A. They play roles in
      innate immunity and inflammatory responses. CONCLUSIONS: Using nCounter and SL,
      we validated the altered expression of multiple mRNAs by benzene and identified
      gene pairs predictive of exposure to benzene at levels below the US occupational
      standard of 1ppm.

PMID- 30300413
TI  - Staged hybrid procedure versus radiofrequency catheter ablation in the treatment
      of atrial fibrillation.
AB  - The treatment effect of the hybrid procedure, consisting of a thoracoscopic
      ablation followed by an endocardial radiofrequency catheter ablation (RFCA), is
      unclear. A total of 117 ablation-naive patients who underwent either the staged
      hybrid procedure (n = 72) or RFCA alone (n = 105) for drug-refractory, non
      valvular persistent or long-standing persistent atrial fibrillation (AF) were
      enrolled. The primary outcome is occurrence of total atrial arrhythmia, defined
      as a composite of AF, sustained atrial tachycardia (AT), and atypical atrial
      flutter (AFL) after index procedure. The mean age was 52.7 years. Eighty-four
      percentage of the patients were male. Patients with prior history of stroke and
      long-standing persistent AF were more prevalent in the hybrid group than RFCA
      group. The left atrial volume index was larger in the hybrid group (P<0.001).
      During 2.1 years of median follow-up, the incidence of total atrial arrhythmia
      was not different between the two groups (32.5% vs. 35.7%; adjusted hazard ratio:
      0.64; 95% confidence interval: 0.36-1.14; P = 0.13). The AF recurrence was
      significantly lower in the hybrid group than in the RFCA group (29.6% vs. 34.9%;
      adjusted HR: 0.53; 95% CI: 0.29-0.99; P = 0.046). The hospital stay was longer in
      the hybrid group than in the RFCA group (11 days vs. 4 days; P<0.001). A staged
      hybrid procedure may be an alternative choice for drug-refractory persistent AF,
      but it is no more effective than RFCA alone to eliminate atrial arrhythmias.
      Considering the long-length of stay and the morbidity, careful consideration
      should be given in selection of treatment strategy.

PMID- 30300414
TI  - Parameters that remain consistent independent of pausing before gait-initiation
      during normal rise-to-walk behaviour delineated by sit-to-walk and sit-to-stand
      and-walk.
AB  - BACKGROUND: Rising-to-walk is an everyday transitional movement task rarely
      employed in gait rehabilitation. Sit-to-walk (STW) and sit-to-stand-and-walk
      (STSW), where a pause separates sit-to-stand and gait-initiation (GI) represent
      extremes of rising-to-walk behaviour. Delayed GI can indicate pathological
      impairment but is also observed in healthy individuals. We hypothesise that
      healthy subjects express consistent biomechanical parameters, among others that
      differ, during successful rising-to-walk task performance regardless of
      behaviour. This study therefore sought to identify if any parameters are
      consistent between STW and STSW in health because they represent normal rise-to
      walk performance independent of pause, and also because they represent candidate
      parameters sensitive enough to monitor change in pathology. METHODS: Ten healthy
      volunteers performed 5 trials of STW and STSW. Event timing, ground-reaction
      forces (GRFs), whole-body-centre-of-mass (BCoM) displacement, and centre-of
      pressure (CoP) to extrapolated BCoM (xCoM) distance (indicator of positional
      stability) up to the 3rd step were compared between-tasks with paired t-tests.
      For consistent parameters; agreement between-tasks was assessed using Bland
      Altman analyses and minimal-detectable-change (MDC) calculations. RESULTS: Mean
      vertical GRFs, peak forward momentum and fluidity during rising; CoP-xCoM
      separation at seat-off, upright, GI-onset, and steps1-2; and forward BCoM
      velocity were all significantly greater in STW. In contrast, peak BCoM vertical
      momentum, flexion-momentum time, and 3rd step stability were consistent between
      tasks and yielded acceptable reliability. CONCLUSION: STW is a more challenging
      task due to the merging of rising with GI reflected by greater CoP-xCoM
      separation compared to STSW indicative of more positional instability. However,
      BCoM vertical momentum, flexion-momentum time, and step3 stability remained
      consistent in healthy individuals and are therefore candidates with which to
      monitor change in gait rehabilitation following pathology. Future studies should
      impose typical pause-durations observed in pathology upon healthy subjects to
      determine if the parameters we have identified remain consistent.

PMID- 30300415
TI  - The usefulness of narrow band imaging in the assessment of laryngeal
      papillomatosis.
AB  - OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis (RRP) is a benign
      disease caused by human papillomavirus 6 and 11. The characteristic feature of
      this disease are wart-like lesions covering the respiratory epithelium with a
      predilection for the larynx. There is no curative treatment for the disease. The
      goal of the treatment is a total surgical removal of the papillomatous lesions in
      order to reduce the number of relapses. Therefore, a good visualization method of
      papillomas is crucial during surgery. The aim of the study was to compare the
      accuracy of narrow band imaging (NBI) to the use of white light alone in
      detecting RRP. METHODS: The study was carried out between April 2013 and November
      2015 at Poznan University of Medical Sciences, Department of Otolaryngology,
      Poland. Rigid endoscopy with conventional white light (WL) and NBI (CV-260SL
      processor and CLV- 260SL light source, Olympus Optical Co. Ltd, Tokyo, Japan) was
      performed in all patients during direct laryngoscopy. All anatomical sites of the
      larynx and trachea were assessed using the Dikkers scale and Derkay total site
      scoring system with WL and NBI. The consensus was reached as to the number of
      lesions seen in WL compared to NBI. RESULTS: During 36 microlaryngoscopies, the
      number of papillomas detected in the larynx (by Derkay total site score) differed
      significantly between white light endoscopy and NBI (Wilcoxon test p = 0.000655).
      In endoscopy with NBI, a mean of 1.3 more papillomas in Derkay total site score
      was detected in comparison to white light endoscopy NBI showed additional areas
      of diseased tissue in 15/36 (41.67%) patients. CONCLUSIONS: NBI as an additional
      tool during microlaryngoscopy can improve the detection of papillomatous lesions.

PMID- 30300417
TI  - A multi-agent system for distributed multi-project scheduling with two-stage
      decomposition.
AB  - A two-stage decomposition approach based on a novel multi-agent system (MAS) is
      proposed for the distributed resource constrained multi-project scheduling
      problem (DRCMPSP). In stage one, from the point of view of each local project
      manager, a forward-backward hybrid genetic algorithm (FBHGA) is developed to
      generate an initial local schedule with the objective of minimizing individual
      project makespan. In stage two, from the global perspective of project management
      office, a sequential game-based negotiation mechanism is employed to eliminate
      global resource conflicts with the objective of minimizing total tardiness cost
      (TTC). The proposed approach is tested on 140 benchmark problem instances.
      According to the computational results, high-quality local project schedules can
      be obtained by FBHGA in stage one. Furthermore, it is observed that our method is
      capable of dealing with various complex multi-project instances under different
      degrees of resource conflicts in reasonable CPU running time. Compared to the
      existing decentralized methods for DRCMPSP, the proposed approach with sequential
      game-based negotiation mechanism shows the superiority in producing multi-project
      schedules with lower TTC, especially for large-size and strong conflicting
      instances.

PMID- 30300416
TI  - Effect of sensor location on continuous intraperitoneal glucose sensing in an
      animal model.
AB  - BACKGROUND: In diabetes research, the development of the artificial pancreas has
      been a major topic since continuous glucose monitoring became available in the
      early 2000's. A prerequisite for an artificial pancreas is fast and reliable
      glucose sensing. However, subcutaneous continuous glucose monitoring carries the
      disadvantage of slow dynamics. As an alternative, we explored continuous glucose
      sensing in the peritoneal space, and investigated potential spatial differences
      in glucose dynamics within the peritoneal cavity. As a secondary outcome, we
      compared the glucose dynamics in the peritoneal space to the subcutaneous tissue.
      MATERIAL AND METHODS: Eight-hour experiments were conducted on 12 anesthetised
      non-diabetic pigs. Four commercially available amperometric glucose sensors
      (FreeStyle Libre, Abbott Diabetes Care Ltd., Witney, UK) were inserted in four
      different locations of the peritoneal cavity and two sensors were inserted in the
      subcutaneous tissue. Meals were simulated by intravenous infusions of glucose,
      and frequent arterial blood and intraperitoneal fluid samples were collected for
      glucose reference. RESULTS: No significant differences were discovered in glucose
      dynamics between the four quadrants of the peritoneal cavity. The intraperitoneal
      sensors responded faster to the glucose excursions than the subcutaneous sensors,
      and the time delay was significantly smaller for the intraperitoneal sensors, but
      we did not find significant results when comparing the other dynamic parameters.

PMID- 30300418
TI  - Correction: A multicenter, randomized controlled trial of individualized
      occupational therapy for patients with schizophrenia in Japan.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0193869.].

PMID- 30300419
TI  - Genomic profiling supports the diagnosis of primary ciliary dyskinesia and
      reveals novel candidate genes and genetic variants.
AB  - Primary ciliary dyskinesia (PCD) is a rare inherited autosomal recessive or X
      linked disorder that mainly affects lungs. Dysfunction of respiratory cilia
      causes symptoms such as chronic rhinosinusitis, coughing, rhinitis, conductive
      hearing loss and recurrent lung infections with bronchiectasis. It is now well
      known that pathogenic genetic changes lead to ciliary dysfunction. Here we report
      usage of clinical-exome based NGS approach in order to reveal underlying genetic
      causes in cohort of 21 patient with diagnosis of PCD. By detecting 18 (12 novel)
      potentially pathogenic genetic variants, we established the genetic cause of 11
      (9 unrelated) patients. Genetic variants were detected in six PCD disease-causing
      genes, as well as in SPAG16 and SPAG17 genes, that were not detected in PCD
      patients so far, but were related to some symptoms of PCD. The most frequently
      mutated gene in our cohort was DNAH5 (27.77%). Identified variants were in
      homozygous, compound heterozygous and trans-heterozygous state. For detailed
      characterization of one novel homozygous genetic variant in DNAI1 gene (c.
      947_948insG, p. Thr318TyrfsTer11), RT-qPCR and Western Blot analysis were
      performed. Molecular diagnostic approach applied in this study enables analysis
      of 29 PCD disease-causing and related genes. It resulted in mutation detection
      rate of 50% and enabled discovery of twelve novel mutations and pointed two
      possible novel PCD candidate genes.

PMID- 30300420
TI  - The impact and cost-effectiveness of controlling cholera through the use of oral
      cholera vaccines in urban Bangladesh: A disease modeling and economic analysis.
AB  - BACKGROUND: Cholera remains an important public health problem in major cities in
      Bangladesh, especially in slum areas. In response to growing interest among local
      policymakers to control this disease, this study estimated the impact and cost
      effectiveness of preventive cholera vaccination over a ten-year period in a high
      risk slum population in Dhaka to inform decisions about the use of oral cholera
      vaccines as a key tool in reducing cholera risk in such populations.
      METHODOLOGY/PRINCIPAL FINDINGS: Assuming use of a two-dose killed whole-cell oral
      cholera vaccine to be produced locally, the number of cholera cases and deaths
      averted was estimated for three target group options (1-4 year olds, 1-14 year
      olds, and all persons 1+), using cholera incidence data from Dhaka, estimates of
      vaccination coverage rates from the literature, and a dynamic model of cholera
      transmission based on data from Matlab, which incorporates herd effects. Local
      estimates of vaccination costs minus savings in treatment costs, were used to
      obtain incremental cost-effectiveness ratios for one- and ten-dose vial sizes.
      Vaccinating 1-14 year olds every three years, combined with annual routine
      vaccination of children, would be the most cost-effective strategy, reducing
      incidence in this population by 45% (assuming 10% annual migration), and costing
      was $823 (2015 USD) for single dose vials and $591 (2015 USD) for ten-dose vials
      per disability-adjusted life year (DALY) averted. Vaccinating all ages one year
      and above would reduce incidence by >90%, but would be 50% less cost-effective
      ($894-1,234/DALY averted). Limiting vaccination to 1-4 year olds would be the
      least cost-effective strategy (preventing only 7% of cases and costing $1,276
      $1,731/DALY averted), due to the limited herd effects of vaccinating this small
      population and the lower vaccine efficacy in this age group.
      CONCLUSIONS/SIGNIFICANCE: Providing cholera vaccine to slum populations in Dhaka
      through periodic vaccination campaigns would significantly reduce cholera
      incidence and inequities, and be especially cost-effective if all 1-14 year olds
      are targeted.

PMID- 30300421
TI  - Femoral antecurvation-A 3D CT Analysis of 1232 adult femurs.
AB  - INTRODUCTION: For optimal treatment of femoral fractures, it is essential to
      understand the anatomical antecurvation of the human femur. Recent clinical
      studies have highlighted the problem of distal anterior encroachment or even
      perforation of the nail tip. The aim of this study was to accurately describe the
      femoral antecurvation in a large cohort. Another objective was to identify the
      most important influences on femoral antecurvation, such as age, femur length,
      gender and ethnicity. METHODS: A three dimensional modelling and analytical
      technology was applied for the analysis of 1,232 femurs. Individual femoral
      antecurvation was precisely computed to determine whether gender, femur length,
      age, ethnicity or body mass index influence the radius of curvature (ROC).
      RESULTS: The calculated mean ROC for all femurs was 943 mm. The lowest ROC of 826
      mm was found in female Asian femurs. A regression analysis demonstrated that age
      and femur length could predict the variability of the curvature, with femoral
      length as most powerful predictor. A matched pair subgroup analysis between
      Asians and Caucasians could not show any significant differences of ROC values.
      CONCLUSIONS: The mean radius of the femoral antecurvation may be smaller than
      previously reported revealing a significant mismatch between the actual
      individual anatomy and existing implants. In opposite to existing literature,
      this study suggests, that antecurvation differences between various ethnicities
      may exclusively be attributed to differences in femoral length and age. The
      findings of this study may be found helpful in the development of novel designs
      for intra- and extramedullary implants.

PMID- 30300423
TI  - Scaling of speed with group size in cooperative transport by the ant Novomessor
      cockerelli.
AB  - Working together allows social animals to accomplish tasks beyond the abilities
      of solitary individuals, but the benefits of cooperation must be balanced with
      the costs of coordination. Many ant species form cooperative groups to transport
      items too large for a single ant. However, transport by groups is often slower
      and less efficient than that of lone ants, for reasons that remain poorly
      understood. We tested the hypothesis that groups are slower when porters must
      encircle the load to carry it, because this arrangement places ants in a variety
      of postures relative to the load and the direction of travel. Porters may
      therefore have difficulty maximizing individual forces and aligning them with
      those of other group members. Experiments on the desert ant Novomessor
      cockerelli, an adept cooperative transporter, did not support this hypothesis.
      Groups ranging in size from one to four ants were induced to carry loads such
      that all porters were aligned with one another. Load weight was adjusted so that
      all porters pulled the same per capita weight, but lone porters were nonetheless
      faster than groups of any size. As group size increased, porters persisted in
      carrying the load for longer periods before letting go. We used simulations to
      explore a scenario in which ants vary in their intrinsic speed and the group's
      speed is limited by that of its slowest member. This proposed mechanism is
      analogous to other social groups where group efficiency is determined by the
      weakest link. We discuss how interactions among porters, mediated by the load
      itself, might explain such a constraint.

PMID- 30300422
TI  - Patient-centered primary care and self-rated health in 6 Latin American and
      Caribbean countries: Analysis of a public opinion cross-sectional survey.
AB  - BACKGROUND: Despite the substantial attention to primary care (PC), few studies
      have addressed the relationship between patients' experience with PC and their
      health status in low-and middle-income countries. This study aimed to (1) test
      the association between overall patient-centered PC experience (OPCE) and self
      rated health (SRH) and (2) identify specific features of patient-centered PC
      associated with better SRH (i.e., excellent or very good SRH) in 6 Latin American
      and Caribbean countries. METHODS AND FINDINGS: We conducted a secondary analysis
      of a 2013 public opinion cross-sectional survey on perceptions and experiences
      with healthcare systems in Brazil, Colombia, El Salvador, Jamaica, Mexico, and
      Panama; the data were nationally representative for urban populations. We
      analyzed 9 features of patient-centered PC. We calculated OPCE score as the
      arithmetic mean of the PC features. OPCE score ranged from 0 to 1, where 0 meant
      that the participant did not have any of the 9 patient-centered PC experiences,
      while 1 meant that he/she reported having all these experiences. After testing
      for interaction on the additive scale, we analyzed countries pooled for aim 1,
      with an interaction term for Mexico, and each country separately for aim 2. We
      used multiple Poisson regression models double-weighted by survey and inverse
      probability weights to deal with the survey design and missing data. The study
      included 6,100 participants. The percentage of participants with excellent or
      very good SRH ranged from 29.5% in Mexico to 52.4% in Jamaica. OPCE was
      associated with reporting excellent or very good SRH in all countries: adjusting
      for socio-demographic and health covariates, patients with an OPCE score of 1 in
      Brazil, Colombia, El Salvador, Jamaica, and Panama were more likely to report
      excellent or very good SRH than those with a score of 0 (adjusted prevalence
      ratio [aPR] 1.61, 95% CI 1.37-1.90, p < 0.001); in Mexico, this association was
      even stronger (aPR 4.27, 95% CI 2.34-7.81, p < 0.001). The specific features of
      patient-centered PC associated with better SRH differed by country. The
      perception that PC providers solve most health problems was associated with
      excellent or very good SRH in Colombia (aPR 1.38, 95% CI 1.01-1.91, p = 0.046)
      and Jamaica (aPR 1.21, 95% CI 1.02-1.43, p = 0.030). Having a provider who knows
      relevant medical history was positively associated with better SRH in Mexico (aPR
      1.47, 95% CI 1.03-2.12, p = 0.036) but was negatively associated with better SRH
      in Brazil (aPR 0.71, 95% CI 0.56-0.89, p = 0.003). Finally, easy contact with PC
      facility (Mexico: aPR 1.35, 95% CI 1.04-1.74, p = 0.023), coordination of care
      (Mexico: aPR 1.53, 95% CI 1.19-1.98, p = 0.001), and opportunity to ask questions
      (Brazil: aPR 1.42, 95% CI 1.11-1.83, p = 0.006) were each associated with better
      SRH. The main study limitation consists in the analysis being of cross-sectional
      data, which does not allow making causal inferences or identifying the direction
      of the association between the variables. CONCLUSIONS: Overall, a higher OPCE
      score was associated with better SRH in these 6 Latin American and Caribbean
      countries; associations between specific characteristics of patient-centered PC
      and SRH differed by country. The findings underscore the importance of high
      quality, patient-centered PC as a path to improved population health.

PMID- 30300424
TI  - Southernmost records of Escarpia spicata and Lamellibrachia barhami (Annelida:
      Siboglinidae) confirmed with DNA obtained from dried tubes collected from
      undiscovered reducing environments in northern Chile.
AB  - Deep-sea fishing bycatch enables collection of samples of rare species that are
      not easily accessible, for research purposes. However, these specimens are often
      degraded, losing diagnostic morphological characteristics. Several tubes of
      vestimentiferans, conspicuous annelids endemic to chemosynthetic environments,
      were obtained from a single batch of deep-sea fishing bycatch at depths of around
      1,500 m off Huasco, northern Chile, as part of an ongoing study examining bycatch
      species. DNA sequences of the mitochondrial cytochrome c oxidase subunit I (COI)
      gene and an intron region within the hemoglobin subunit B2 (hbB2i) were
      successfully determined using vestimentiferans' dried-up tubes and their degraded
      inner tissue. Molecular phylogenetic analyses based on DNA sequence identified
      the samples as Escarpia spicata Jones, 1985, and Lamellibrachia barhami Webb,
      1969. These are the southernmost records, vastly extending the geographical
      ranges of both species from Santa Catalina Island, California to northern Chile
      for E. spicata (over 8,000 km), and from Vancouver Island Margin to northern
      Chile for L. barhami (over 10,000 km). We also determined a 16S rRNA sequence of
      symbiotic bacteria of L. barhami. The sequence of the bacteria is the same as
      that of E. laminata, Lamellibrachia sp. 1, and Lamellibrachia sp.2 known from the
      Gulf of Mexico. The present study provides sound evidence forthe presence of
      reducing environments along the continental margin of northern Chile.

PMID- 30300426
TI  - Initial Fluid Therapy in Pediatric Diabetic Ketoacidosis: A comparison of
      Hypertonic Saline Solution and Normal Saline Solution.
AB  - INTRODUCTION: The optimal fluid therapy in children with DKA is a matter of
      debate, especially if we take into account its association with cerebral edema,
      the most important complication. Hypertonic Saline Solution is used in the
      treatment of cerebral edema, and also has been used for volume resuscitation in
      children with shock. AIM OF STUDY: To compare the effects of 3% saline and 0.9%
      saline solutions on changes in vital parameters, sodium and chloride levels,
      lactate and pH; time needed for the correction of hyperglycemia; time needed for
      the control of ketoacidosis and incidence of cerebral edema. METHODS: Open-label
      prospective RCT in which 40 children with moderate to severe DKA were randomized
      to receive either 3% saline or 0.9% saline as initial fluid therapy. RESULTS:
      There was no significant difference between the two groups in the clinical vital
      parameters, time for the correction of hyperglycemia and the resolution of
      acidosis. Patients in the 3% saline group had a higher increase in sodium and
      chloride from baseline compared to the 0.9% saline group. The acidemia was noted
      to worsen in both groups after the initiation of fluid therapy, which was not
      associated with clinical deterioration. The frequency of cerebral edema was
      similar in both groups. CONCLUSIONS: Both 0.9% saline and 3% saline were equally
      effective as initial fluid in children with DKA with respect to hemodynamic
      improvement, the resolution of acidosis and the correction of hyperglycemia, but
      the use of 3% saline solution did not preclude the development of cerebral edema
      and has the potential to cause hypernatremia, hyperchloremia and hyperchloremic
      metabolic acidosis.

PMID- 30300425
TI  - Altered white matter connectivity in patients with schizophrenia: An
      investigation using public neuroimaging data from SchizConnect.
AB  - Several studies have produced extensive evidence on white matter abnormalities in
      schizophrenia (SZ). However, optimum consistency and reproducibility have not
      been achieved, and reported low white matter tract integrity in patients with SZ
      varies between studies. A whole-brain imaging study with a large sample size is
      needed. This study aimed to investigate white matter integrity in the corpus
      callosum and connections between regions of interests (ROIs) in the same
      hemisphere in 122 patients with SZ and 129 healthy controls with public
      neuroimaging data from SchizConnect. For each diffusion-weighted image (DWI), two
      tensor full-brain tractography was performed; DWIs were parcellated by processing
      and registering T1 images with FreeSurfer and Advanced Normalization Tools. White
      matter query language was used to extract white matter fiber tracts. We evaluated
      group differences in means of diffusion measures between the patients and
      controls, and correlations of diffusion measures with the severity of clinical
      symptoms and cognitive impairment in the patients using the Positive and Negative
      Syndrome Scale (PANSS), a letter-number sequencing (LNS) test, vocabulary test,
      letter fluency test, category fluency test, and trail-making test, part A. To
      correct for multiple comparisons, a false discovery rate of q < 0.05 was applied.
      In patients with SZ, we observed significant radial diffusivity (RD) and trace
      (TR) increases in left thalamo-occipital tracts and the right uncinate fascicle,
      and a significant RD increase in the right middle longitudinal fascicle (MDLF)
      and the right superior longitudinal fascicle ii. Correlations were present
      between TR of left thalamo-occipital tracts, and the letter fluency test and the
      LNS test, and RD in the right MDLF and PANSS positive subscale score. However,
      these correlations were not significant after correction for multiple
      comparisons. These results indicated widespread white matter fiber tract
      abnormalities in patients with SZ, contributing to SZ pathophysiology.

PMID- 30300427
TI  - Assessment pf physical fitness of 8 and 9-year-old children from Szczecin,Poland,
      involved in the obesity prevention program - pilot study.
AB  - INTRODUCTION: Increasing incidence of excess weight and poor physical fitness of
      children validates the need for preventive actions. The Szczecin municipality
      (gmina Szczecin) runs the "Odwazna osemka" ("The Brave Eight") program -
      Prevention of excess weight and obesity in 8 and 9-year-old children attending
      elementary school in Szczecin, Poland. AIM: The assessment of physical fitness as
      well as the prevalence and intensity of excess body weight and blood pressure
      rates among the 8 and 9-year-old children attending elementary school in
      Szczecin, Poland. MATERIAL AND METHODS: Between 6th December 2016 and 3rd
      December 2017, 3407 8 and 9-year-old children were examined (1757 girls and 1650
      boys). BMI (Body Mass Index) as well as WHR (Waist Hip Ratio) were calculated.
      All the children were assessed according to criteria established by the
      International Obesity Task Force (IOTF). The examination included basic
      anthropometric measurements, such as: body height and weight, waist and hip
      circumference, blood pressure, body constitution analysis, and physical fitness
      assessment. RESULTS: Excess body weight was diagnosed in 822 patients, which is
      24.1% of the examined population. 369 patients were diagnosed with elevated blood
      pressure (10.8%). Very poor physical fitness - test abandoned before the
      completion (HR>180/min), was diagnosed in 151 children (4.5%), very poor physical
      fitness was diagnosed in 234 children (7%), poor physical fitness was diagnosed
      in 827 children (24.9%), sufficient physical fitness was diagnosed in 961
      children (29.2%), good physical fitness was diagnosed in 650 children (19.5%),
      very good physical fitness was diagnose in 428 children (12.8%) and excellent in
      70 children (2.1%). CONCLUSION: The fact of unsatisfactory physical fitness and
      excess body weight in children from Szczecin is unsettling. There is ceratainly a
      need for preventive measures in the broad sense.

PMID- 30300428
TI  - [Nutritional habits of 11-12-year-old swimmers against non-athlete peers - a
      pilot study].
AB  - INTRODUCTION: Quality and quantity of food, consumed by a child have a great
      influence on his biological development. Dietary habits of children often do not
      meet criteria suggested by health institutions and schools. Nutrition of a child,
      involved in competitive sport should be rationally planned and obeyed. AIM:
      Comparison of dietary habits among two groups children: practicing swimming and
      non-athletes. MATERIALS AND METHOD: Research group consisted of 11-12-year-old
      children attending the same public primary school. Forty six students engaged in
      swimming training and forty two non-athletes were examined. The following
      anthropometrics variables had been measured: body height, body mass, percent body
      fat and body mass index. Dietary habits of the children were assessed by the
      survey, created on the basis of a tools available in literature. RESULTS:
      Children of both groups differed essentially in terms of percent body fat.
      Anyway, their body proportions meet the referred standards. A few differences
      were discovered in nutritional patterns among swimmers and non-athletes. Young
      swimmers more often consumed dinners at school. Moreover, swimming pupils ate
      dairy products more often than their peers, but ate fish less often. Non-athletes
      declared consumption of sweets more often when compared to the swimmers.
      CONCLUSIONS: Results of this study revealed insufficient number of consumed meal
      portions in both groups. There is a need of permanent nutritional education,
      provided by parents, teachers at school and sports coaches.

PMID- 30300429
TI  - [Body fat measurements using bioelectrical impedance in pediatric patientstreated
      with hematopoietic cell transplantation].
AB  - INTRODUCTION: In patients who have undergone hematopoietic cell transplantation
      (HCT), the metabolic syndrome may develop without obesity defined by Body Mass
      Index (BMI). AIM OF THE STUDY: The aim of the study was to compare body fat
      parameters measured using bioelectrical impedance (BIA) and using standard
      parameters of obesity in patients treated with HCT and healthy controls. MATERIAL
      AND METHODS: We compared body fat (BF) and body fat percentage (BF%) measured
      using BIA in 44 patients before HCT and 28 patients after HCT, versus 26
      controls. We also compared BMI and other BIA parameters in these groups of
      patients. RESULTS: The differences in BF and BF% between the patients before HCT
      and controls were not significant, while both BF and BF% were significantly lower
      in patients after HCT than in the control group. No significant differences in
      standard clinical obesity parameters were found in the patients before HCT, and
      in the patients after HCT, compared with the controls. The differences in other
      BIA parameters between the patients before HCT and the controls were not
      significant, while in the patients after HCT some parameters were significantly
      lower. CONCLUSION: Significant differences in BF and BF% in the patients after
      HCT compared with healthy controls suggest that BIA may be useful in screening
      for body fat abnormalities in patients after HCT.

PMID- 30300430
TI  - Endocrine disruptor compounds in environment: As a danger for children health.
AB  - Endocrine disrupting compounds (EDCs) are heterogenous in structure and include
      synthetic organic compounds such as pharmaceutical agents, plant protection
      products, plastics, plasticizers, polychlorinated biphenyls, dioxins, flame
      retardants, and antifoulant paint additive, as well, as natural plant-derived
      EDCs termed phytoestrogens and mycoestrogens. Children and adults are exposed
      daily to EDCs during drinking contaminated water, eating, breathing polluted air
      or direct contact with chemicals. Prenatal and perinatal period, infancy,
      childhood, and puberty are critical time of development during which maturing
      systems are particularly sensitive to hormonal disruptions (small elimination of
      xenobiotics). Exposure to environmental chemicals with estrogenic or
      antiandrogenic action may disrupt female reproductive tract development, also
      testosterone synthesis and sexual differentiation, leading to adult testis
      dysfunction and infertility. What is important, today there is still no
      definitive risk assessment tool for EDCs.

PMID- 30300431
TI  - [The impact of VDR gene polymorphisms on obesity, metabolic changes, bone mass
      disorders and neoplastic processes].
AB  - Vitamin D activity is controlled by its receptor (VDR) located in many cells of
      the body. The presence of VDR in numerous cellular pathways suggests its
      important role in the etiology and development of many diseases. Increased risk
      of obesity, metabolic disturbances, bone mass disturbances and neoplasia among
      certain VDR alleles has been proven. The importance of VDR in the etiopathology
      of obesity is associated with the occurrence of polymorphisms: Fok1, Bsm1, Apa1,
      Taq1. VDR expression in adipocytes plays a role in the regulation of energy
      metabolism and the induction of obesity. Vitamin D and VDR polymorphisms can
      participate in the development of many metabolic disorders. The VDR gene is one
      of the better researched genes among patients with type 1 diabetes. The action of
      vitamin D affects the proper functioning and development of the skeletal system.
      Vitamin D has an effect on bone remodeling through its receptor and its
      polymorphisms: Apa1, Bsm1, Taq1, Fok1 and Cdx2. The identification and diagnosis
      of VDR varieties gives the possibility of early detection of the risk of
      osteoporosis or individual predisposition to its development. There is a high
      variability in the results of individual VDR polymorphisms in relation to the
      occurrence of osteoporosis among various ethnic groups. The polymorphisms
      important in the neoplastic process include, among others, the polymorphism of
      Fok1, Bsm1, and Taq1. The association of VDR gene polymorphisms with the risk of
      breast cancer (Bsm1, Fok1), prostate cancer (Fok1) and malignant melanoma (Fok1)
      is indicated. The greatest importance in the prognosis is observed in patients
      with prostate cancer (F1), breast cancer (Bsm1, Taq1), malignant melanoma (Bsm1)
      and renal cell carcinoma (Taq1). It is important to identify, describe and
      correlate the occurrence of genetic polymorphisms of the VDR, which will allow
      early diagnosis or prevention of correlative entities correlated with them.

PMID- 30300433
TI  - Poster list.

PMID- 30300432
TI  - Oral prednisolone for management of persistent hypercalcemia afterhypercalcemic
      crisis in the Williams-Beuren syndrome.
AB  - Hypercalcemia may occur in approximately 15% of children with the Williams-Beuren
      syndrome. The episodes of hypercalcemic crisis usually respond well to initial
      hyperhydration, loop diuretics and calcitonin, bisphosphonates, or subsequent
      dialysis. However, many patients suffer from recurrent or persistent
      hypercalcemia after the resolution of the hypercalcemic crisis. Although
      hypercalcemia in the Williams-Beuren syndrome is generally considered transient,
      it may last for several months, result in significant morbidity, and compromise
      physical growth. There are no guidelines for the management of persistent or
      recurrent hypercalcemia in patients with the Williams-Beuren syndrome. In this
      report, we describe our experience of conducting oral corticosteroid therapy in a
      child with the Williams-Beuren syndrome who continued to have hypercalcemia after
      the resolution of the hypercalcemic crisis.

PMID- 30300438
TI  - Long-term effects of delayed graft function duration on function and survival of
      deceased donor kidney transplants.
AB  - INTRODUCTION: Delayed graft function (DGF) is a frequent complication after
      deceased donor kidney transplantation with an impact on the prognosis of the
      transplant. Despite this, long-term impact of DGF on graft function after
      deceased donor kidney transplantation has not been properly evaluated. OBJECTIVE:
      The main objective of this study was to evaluate risk factors for DGF and the
      impact of its occurrence and length on graft survival and function. METHODS: A
      retrospective cohort study was performed in 517 kidney transplant recipients who
      received a deceased donor organ between January 2008 and December 2013. RESULTS:
      The incidence of DGF was 69.3% and it was independently associated with donor's
      final serum creatinine and age, cold ischemia time, use of antibody induction
      therapy and recipient's diabetes mellitus. The occurrence of DGF was also
      associated with a higher incidence of Banff >= 1A grade acute rejection (P =
      0.017), lower graft function up to six years after transplantation and lower
      death-censored graft survival at 1 and 5 years (P < 0.05). DGF period longer than
      14 days was associated with higher incidence of death-censored graft loss (P =
      0.038) and poorer graft function (P < 0.001). No differences were found in
      patient survival. CONCLUSIONS: The occurrence of DGF has a long-lasting
      detrimental impact on graft function and survival and this impact is even more
      pronounced when DGF lasts longer than two weeks.

PMID- 30300439
TI  - Aromatic-Diimide-Based n-Type Conjugated Polymers for All-Polymer Solar Cell
      Applications.
AB  - All-polymer solar cells (all-PSCs) have attracted immense attention in recent
      years due to their advantages of tunable absorption spectra and electronic energy
      levels for both donor and acceptor polymers, as well as their superior thermal
      and mechanical stability. The exploration of the novel n-type conjugated polymers
      (CPs), especially based on aromatic diimide (ADI), plays a vital role in the
      further improvement of power conversion efficiency (PCE) of all-PSCs. Here,
      recent progress in structure modification of ADIs including naphthalene diimide
      (NDI), perylene diimide (PDI), and corresponding derivatives is reviewed, and the
      structure-property relationships of ADI-based CPs are revealed.

PMID- 30300440
TI  - Pharmacokinetics of the Meropenem Component of Meropenem-Vaborbactam in the
      Treatment of KPC-Producing Klebsiella pneumoniae Bloodstream Infection in a
      Pediatric Patient.
AB  - Meropenem-vaborbactam is a new beta-lactam/beta-lactamase inhibitor combination
      designed to target Klebsiella pneumoniae carbapenemase (KPC)-producing
      Enterobacteriaceae. Meropenem-vaborbactam was United States Food and Drug
      Administration-approved for complicated urinary tract infections in patients 18
      years of age or older. An understanding of the pharmacokinetics of meropenem when
      given in combination with vaborbactam is important to understanding the dosing of
      meropenem-vaborbactam. In addition, the safety and efficacy of meropenem
      vaborbactam in a pediatric patient have yet to be described in the literature.
      The authors conducted a retrospective single-patient chart review for a 4-year
      old male patient with short bowel syndrome, colostomy and gastrojejunal tube,
      bronchopulmonary dysplasia, and a central line for chronic total parenteral
      nutrition and hydration management, complicated with multiple central line
      associated bloodstream infections (BSIs). The patient was brought to our medical
      center with fever concerning for a BSI. On day 2, the patient was started on
      meropenem-vaborbactam at a dosage of 40 mg/kg every 6 hours infused over 3 hours
      for KPC-producing K. pneumoniae BSI. Meropenem serum concentrations obtained on
      day 5 of meropenem-vaborbactam therapy, immediately following the completion of
      the infusion and 1 hour after the infusion, were 51.3 and 13.6 MUg/ml,
      respectively. Serum concentrations correlated to a volume of distribution of 0.59
      L/kg and a clearance of 13.1 ml/min/kg. Repeat blood cultures remained negative,
      and meropenem-vaborbactam was continued for a total of 14 days. A meropenem
      vaborbactam regimen of 40 mg/kg every 6 hours given over 3 hours was successful
      in providing a target attainment of 100% for meropenem serum concentrations above
      the minimum inhibitory concentration for at least 40% of the dosing interval and
      was associated with successful bacteremia clearance in a pediatric patient.

PMID- 30300441
TI  - Clinical Utility of Methicillin-Resistant Staphylococcus aureus Nasal Screening
      for Antimicrobial Stewardship: A Review of Current Literature.
AB  - Significant clinical and financial consequences are associated with both
      inadequate and unnecessary exposure to broad-spectrum antibiotics. As such,
      antimicrobial stewardship programs seek objective, reliable, and cost-effective
      tests to identify patients at highest or lowest risk for drug-resistant organisms
      to guide empirical antimicrobial selection. Use of methicillin-resistant
      Staphylococcus aureus (MRSA) nasal screening to rule out MRSA in lower
      respiratory tract infections has led to significant reductions in duration of
      vancomycin therapy. The clinical utility of MRSA nasal screening in other types
      of infection remains less clear. This review describes the performance of MRSA
      nasal screening in predicting MRSA infection, highlights practical considerations
      for use of MRSA nasal screening, and provides guidance for incorporating MRSA
      nasal screening into clinical practice. With a high negative predictive value
      when the prevalence of MRSA is low, MRSA nasal screening is a valuable
      antimicrobial stewardship tool with potential applications beyond lower
      respiratory tract infections. In appropriately selected patients, negative MRSA
      nasal screening can prevent initiation or guide discontinuation of anti-MRSA
      therapy. Antimicrobial stewardship programs should develop institutional
      guidelines to promote proper use of MRSA nasal screening. Pharmacists are well
      positioned to assist with education, interpretation, and application of MRSA
      nasal screening results.

PMID- 30300442
TI  - Flexible and Implantable Microelectrodes for Chronically Stable Neural
      Interfaces.
AB  - Implantable electrical probes that can record neural activities at single-neuron
      and sub-millisecond resolution are the most widely applied tools in both
      neuroscience research and neuroprosthetics. However, the structural and
      mechanical mismatch between conventional rigid probes and neural tissues results
      in inflammatory responses and signal degradation over chronic recordings.
      Reducing the cross-sectional footprints and rigidity of the probes can
      effectively improve the long-term stability of neural interfaces. Herein, recent
      progress in the development of implantable microelectrodes for chronically stable
      neural interfaces is highlighted, with a focus on the utilization of advanced
      materials and structural design concepts.

PMID- 30300443
TI  - Nanoenvelopes: Wrapping a Single-Walled Carbon Nanotube with Graphene using an
      Atomic Force Microscope.
AB  - Engineering the morphology and structure of low-dimensional carbon nanomaterials
      is important to study their mechanical and electrical properties and even
      superconductivity. Herein, first the techniques that are used to engineer carbon
      nanotubes, including manipulation, morphology modification, and fabrication of
      complex nanostructures, are reviewed. This is followed by a summary of the
      methods applied to fabricate graphene nanostructures, such as heterostructures
      and nanoenvelopes of graphene. Lastly, an insight into the applications of low
      dimensional-carbon-based electronics is given, such as carbon nanotube (CNT)
      transistors, graphene-based nanoenvelopes, and graphene-contacted CNT field
      effect transistors (FETs), which are promising components in future electronics.

PMID- 30300444
TI  - Advanced Carbon for Flexible and Wearable Electronics.
AB  - Flexible and wearable electronics are attracting wide attention due to their
      potential applications in wearable human health monitoring and care systems.
      Carbon materials have combined superiorities such as good electrical
      conductivity, intrinsic and structural flexibility, light weight, high chemical
      and thermal stability, ease of chemical functionalization, as well as potential
      mass production, enabling them to be promising candidate materials for flexible
      and wearable electronics. Consequently, great efforts are devoted to the
      controlled fabrication of carbon materials with rationally designed structures
      for applications in next-generation electronics. Herein, the latest advances in
      the rational design and controlled fabrication of carbon materials toward
      applications in flexible and wearable electronics are reviewed. Various carbon
      materials (carbon nanotubes, graphene, natural-biomaterial-derived carbon, etc.)
      with controlled micro/nanostructures and designed macroscopic morphologies for
      high-performance flexible electronics are introduced. The fabrication strategies,
      working mechanism, performance, and applications of carbon-based flexible devices
      are reviewed and discussed, including strain/pressure sensors,
      temperature/humidity sensors, electrochemical sensors, flexible conductive
      electrodes/wires, and flexible power devices. Furthermore, the integration of
      multiple devices toward multifunctional wearable systems is briefly reviewed.
      Finally, the existing challenges and future opportunities in this field are
      summarized.

PMID- 30300445
TI  - Population Pharmacokinetics of Gentamicin in Neonates with Hypoxemic-Ischemic
      Encephalopathy Receiving Controlled Hypothermia.
AB  - OBJECTIVE: Identify population pharmacokinetics and pharmacodynamic target
      attainment of gentamicin in neonates with hypoxic-ischemic encephalopathy (HIE)
      undergoing controlled hypothermia (CH). DESIGN: Prospective open-label
      pharmacokinetic study. Gentamicin concentrations were modeled and dosing regimens
      simulated for a 5000-patient neonatal population with HIE receiving CH using
      PMetrics, a nonparametric, pharmacometric modeling, and simulation package for R.
      SETTING: A 189-bed children's tertiary care teaching hospital. RESULTS: Twelve
      patients, 5 (42%) females and 7 (58%) males, met inclusion criteria with a median
      gestation age of 39.9 weeks (interquartile range [IQR] 38.5-40.2 wks) and a
      median birthweight (BW) of 3.3 kg (IQR 3.1-3.7 kg). Gentamicin concentrations
      were best described by a two-compartment model with first-order elimination with
      BW as a covariate on volume of distribution (Vd). The mean total body population
      clearance (CL) was 2.2 +/- 0.7 ml/minute/kg, and the volume of the central
      compartment was 0.44 +/- 0.06 L/kg. The R2 , bias, and precision for the observed
      versus population predicted model were 0.917, 1.15, and 10.9 MUg/ml; the R2 ,
      bias, and precision for the observed versus individual predicted model were
      0.982, -0.132, and 0.932 MUg/ml, respectively. The calculated mean population
      estimate for the total Vd was 0.96 +/- 0.4 L/kg. The dosing regimen that most
      consistently produced a maximum concentration (Cmax ) in the range of 10-12 mg/L
      with a minimum concentration (Cmin ) level less than 2 mg/L was 5 mg/kg/dose
      given every 36 hours. CONCLUSION: These data suggest the population
      pharmacokinetics of gentamicin in neonates with HIE receiving CH have an increase
      in gentamicin CL and are different from previous reports in neonates with HIE not
      receiving CH and/or neonates without HIE. This analysis suggests a dosing regimen
      of 5 mg/kg/dose every 36 hours results in a gentamicin Cmax within the range of
      10-12 mg/L with a Cmin lower than 2 mg/L, which is appropriate for treating
      susceptible gram-negative organisms with minimum inhibitory concentrations of 1
      mg/L or lower.

PMID- 30300447
TI  - Effect of resilience on intolerance of uncertainty in nursing university
      students.
AB  - PURPOSE: Nursing students must cope in a complex and uncertain society. We
      identified the relationship between resilience and intolerance of uncertainty
      (IOU) in nursing students. METHODS: Data were collected from November 10 to 20,
      2016, from 134 Korean nursing students (male = 21, female = 113; first-year = 39,
      second-year = 39, third-year = 35, and fourth-year = 21), using a questionnaire.
      The measures in this study included resilience and IOU. RESULTS: Differences in
      IOU relating to participants' general characteristics showed that IOU was high
      when the major satisfaction was rated as "middle" rather than "high."
      Participants' IOU was significantly negatively correlated with the following
      resilience subdomains: self-regulation skills, interpersonal skills, and positive
      tendencies. In particular, higher positive tendencies led to lower levels of IOU.
      CONCLUSION: It is vital to devise strategies to advance nursing students'
      satisfaction toward their major and positive tendencies to reduce the level of
      IOU. This will prepare nursing students for various programs and improve their
      outcomes at school.

PMID- 30300446
TI  - The dynamics of cortical GABA in human motor learning.
AB  - KEY POINTS: The ability to learn new motor skills is supported by plasticity in
      the structural and functional organisation of the primary motor cortex in the
      human brain. Changes inhibitory to signalling by GABA are thought to be crucial
      in inducing motor cortex plasticity. This study used magnetic resonance
      spectroscopy (MRS) to quantify the concentration of GABA in human motor cortex
      during a period of motor learning, as well as during a period of movement and a
      period at rest. We report evidence for a reduction in the MRS-measured
      concentration of GABA specific to learning. Further, the GABA concentration early
      in the learning task was strongly correlated with the magnitude of subsequent
      learning: higher GABA concentrations were associated with poorer learning. The
      results provide initial insight into the neurochemical correlates of cortical
      plasticity associated with motor learning, specifically relevant in therapeutic
      efforts to induce cortical plasticity during recovery from stroke. ABSTRACT: The
      ability to learn novel motor skills is a central part of our daily lives and can
      provide a model for rehabilitation after a stroke. However, there are still
      fundamental gaps in our understanding of the physiological mechanisms that
      underpin human motor plasticity. The acquisition of new motor skills is dependent
      on changes in local circuitry within the primary motor cortex (M1). This
      reorganisation has been hypothesised to be facilitated by a decrease in local
      inhibition via modulation of the neurotransmitter GABA, but this link has not
      been conclusively demonstrated in humans. Here, we used 7 T magnetic resonance
      spectroscopy to investigate the dynamics of GABA concentrations in human M1
      during the learning of an explicit, serial reaction time task. We observed a
      significant reduction in GABA concentration during motor learning that was not
      seen in an equivalent motor task lacking a learnable sequence, nor during a
      passive resting task of the same duration. No change in glutamate was observed in
      any group. Furthermore, M1 GABA measured early in task performance was strongly
      correlated with the degree of subsequent learning, such that greater inhibition
      was associated with poorer subsequent learning. This result suggests that higher
      levels of cortical inhibition may present a barrier that must be surmounted in
      order to achieve an increase in M1 excitability, and hence encoding of a new
      motor skill. These results provide strong support for the mechanistic role of
      GABAergic inhibition in motor plasticity, raising questions regarding the link
      between population variability in motor learning and GABA metabolism in the
      brain.

PMID- 30300448
TI  - Persistent inaccuracies in completion of medical certificates of stillbirth: A
      cross-sectional study.
AB  - BACKGROUND: The UK Medical Certificate of Stillbirth (MCS) records information
      relevant to the cause of stillbirth of infants >=24 weeks' gestation. A cross
      sectional audit demonstrated widespread inaccuracies in MCS completion in 2009 in
      North West England. A repeat study was conducted to assess whether practice had
      improved following introduction of a regional care pathway. METHODS: 266 MCS
      issued in 14 North West England obstetric units during 2015 were studied
      retrospectively. Cause of death was assigned following review of information
      available at the time of MCS completion. This was compared to that documented on
      the MCS, and to data from 2009. RESULTS: Twenty-three certificates were excluded
      (20 inadequate data, 3 late miscarriages). 118/243 (49%) MCS contained major
      errors. Agreement between the MCS and adjudicated cause of stillbirth was fair
      (Kappa 0.31; 95% CI 0.24, 0.38) and unchanged from 2009 (0.29). In 2015,
      excluding 34 terminations of pregnancy, the proportion of MCSs documenting
      "unexplained" stillbirths (113/211; 54%) was reduced compared to 2009 (158/213;
      74%); causality could be assigned after case note review in 78% cases.
      Recognition of fetal growth restriction (FGR) as a cause of stillbirth improved
      (2015: 30/211; 14% vs 2009: 1/213; 0.5%), although 71% cases were missed. 47%
      MCSs following termination of pregnancy documented an iatrogenic primary cause of
      death. CONCLUSIONS: Completion of MCSs remains inaccurate, particularly in
      recognition of FGR as a cause of stillbirth. Detailed case note review before
      issuing the MCS could dramatically improve the usefulness of included
      information; evaluation of practitioner education programmes/internal feedback
      systems are recommended.

PMID- 30300450
TI  - Effect of reducing acid-etching duration time on compressive strength and bonding
      of a universal adhesive to calcium silicate cements.
AB  - AIM: To assess the effect of acid-etching duration time on the compressive
      strength, microstructure and shear bond strength of All-Bond Universal adhesive
      to MTA-Angelus (AMTA), and Biodentine (BD). METHODOLOGY: Forty-eight cylindrical
      specimens (4 mm in diameter, 6 mm in height) of AMTA in four groups and 48
      specimens of BD in four groups (n = 12) were prepared and stored for 72 h. The
      control groups were unetched whilst the three experimental groups were acid
      etched for 5, 10 and 15 s, respectively, followed by compressive strength
      testing. The effect of the various acid-etching times on surface micromorphology
      was evaluated under a scanning electron microscope. Similar groups were bonded
      using All-Bond Universal and Aelite Flo and shear bond strength was tested. Data
      were analysed using two-way ANOVA and Tukey tests. RESULTS: 10-s and 15-s acid
      etching reduced the compressive strength of AMTA and BD (P < 0.001), while 5-s
      etching did not (P <= 0.86). In all the groups, BD had greater compressive
      strength compared to AMTA. Contrary to BD, the three etched AMTA groups had
      significantly higher shear bond strength compared to the control group (P <
      0.001), with no significant differences between them. The etched groups of AMTA
      had shear bond strengths comparable to all the BD groups. Scanning electron
      microscope observations indicated variable surface morphologies such as remnant
      crystals and cracking/eroding in all our groups of AMTA; though these differences
      were less prominent for BD. CONCLUSIONS: Shortening the acid-etching time to 5 s
      resulted in a beneficial effect in terms of resin bonding for AMTA while
      preventing the detrimental effect of 10-s and 15-s etching on the compressive
      strength of AMTA and BD. However, the three etching times had no effect on resin
      BD bond.

PMID- 30300451
TI  - Shining light on the paraventricular nucleus: the role of glutamatergic PVN
      neurons in blood pressure control.

PMID- 30300449
TI  - Deferasirox in children with transfusion-dependent thalassemia or sickle cell
      anemia: a large cohort real-life experience from Turkey (REACH-THEM).
AB  - OBJECTIVES: To evaluate the long-term efficacy and safety of deferasirox therapy
      in a large observational cohort of children with transfusion-dependent
      thalassemia (TDT) and sickle cell anemia (SCA) in Turkey. METHODS: This was a
      multicenter, prospective cohort study including TDT and SCA patients aged 2-18
      years with iron overload (>=100 mL/kg of pRBC or a serum ferritin [SF] level
      >1000 MUg/L) receiving deferasirox. Patients were followed for up to 3 years
      according to standard practice. RESULTS: 439 patients were evaluated (415 [94.5%]
      TDT, 143 [32.6%] between 2-6 years). SF levels consistently and significantly
      decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5
      MUg/L (p<0.001). SF decreases were noted in TDT (1804.9 to 1241 MUg/L), SCA
      (1655.5 to 1260 MUg/L), and across age groups 2-6 years (1971.5 to 1499 MUg/L), 7
      12 years (1688.5 to 1159.8 MUg/L), and 13-18 years (1496.5 to 1107 MUg/L). SF
      decreases were also noted for all deferasirox dose groups but only significant in
      patients with doses >=30 mg/kg/day (n=120, -579.6 median reduction, p<0.001).
      Only 9 (2%) patients had adverse events suspected to be related to deferasirox.
      Serum creatinine slightly increased but remained within the normal range.
      CONCLUSIONS: Deferasirox has long-term efficacy and safety in children with TDT
      and SCA, although higher doses (>=30 mg/kg/day) may be required to achieve iron
      balance. This article is protected by copyright. All rights reserved.

PMID- 30300452
TI  - Better Guidelines Needed for Cancer Survivorship Management.

PMID- 30300453
TI  - Patients with MELAS not only require treatment of stroke-like episodes but a
      comprehensive individual and family management.

PMID- 30300454
TI  - Differences between chronic and nonchronic depression: Systematic review and
      implications for treatment.
AB  - BACKGROUND: There is still uncertainty if and to what extent chronic depression
      (CD) presents with specific features especially in contrast to the nonchronic
      course of major depressive disorder (non-CD). This systematic review aims to
      summarize the existing literature regarding sociodemographic factors,
      psychopathology, and course of disease in patients with CD in comparison to
      patients with non-CD. METHODS: A structured database search (MEDLINE, PsycINFO,
      Web of Science, CENTRAL) was performed. All studies comparing CD with non-CD
      patients were included. Twenty-eight studies, including cohort studies, cross
      sectional studies, and observational studies, were identified in which both
      subgroups were diagnosed according to DSM-IV or DSM-5, respectively. Primary
      outcome were group comparisons focused on sociodemographic factors, childhood
      adversity, onset of the disorder, comorbidities, severity and course of the
      depressive symptoms, and specific psychopathology. RESULTS: Patients with CD had
      an earlier onset of depressive symptoms, higher rates of psychiatric
      comorbidities, and a complicated treatment course (e.g., higher rates of
      suicidality) compared to non-CD. We also found some evidence for specific
      features in the psychopathology of CD patients (submissive and hostile
      interpersonal styles) in contrast to non-CD patients. Results were inconsistent
      with regard to childhood maltreatment. No differences were found regarding the
      severity of depressive symptoms and most sociodemographic factors. CONCLUSION:
      Despite some inconsistencies, the results of this review verified important
      differences between CD and non-CD. However, future research is needed to
      characterize especially the specific psychopathology of CD in comparison to non
      CD patients to develop more tailored treatment strategies.

PMID- 30300455
TI  - Disturbed sleep in cluster headache is not the result of transient processes
      associated with the cluster period.
AB  - BACKGROUND AND PURPOSE: Cluster headache (CH) is characterized by severe,
      unilateral attacks of pain and a high nocturnal attack burden. It remains unknown
      whether perturbations of sleep are solely present during the CH bout. Therefore,
      we aimed to investigate differences in sleep between the bout and remission
      period in patients with episodic CH and, secondly, to compare patients in the two
      phases with controls. METHODS: Patients with episodic CH (aged 18-65 years),
      diagnosed according to the International Classification of Headache Disorders 2nd
      edition, were admitted for polysomnography at the Danish Center for Sleep
      Medicine in bout and in remission. The macrostructure of sleep, including
      arousals, breathing parameters, limb movements and periodic limb movements, was
      compared with 25 age-, sex- and body mass index-matched healthy controls.
      RESULTS: There were no differences in any of the sleep parameters for patients in
      bout (n = 32) compared with patients in remission (n = 23). Attacks were
      unrelated to sleep stages, presence of apnea episodes, periodic limb movements,
      limb movements and arousals. In bout, patients had longer sleep latency (18.8 vs.
      11.7 min, P < 0.05) and rapid eye movement sleep latency (1.7 vs. 1.2 h, P <
      0.05) than controls and sleep efficiency was lower (82.5% vs. 86.5%, P < 0.05).
      Patients in remission only had a longer sleep latency compared with controls
      (17.5 vs. 11.7 min, P < 0.01). CONCLUSIONS: The results support the presence of a
      continuing or slowly recovering disturbance of sleep outside the bout rather than
      a disturbance occurring secondary to attacks. Further, we confirm that there is
      no relation between CH attacks and specific sleep stages or between CH and
      breathing parameters.

PMID- 30300456
TI  - "Green" UV-LED gel nail polishes from bio-based materials.
AB  - OBJECTIVE: Gel nail polishes represent an advanced class of nail polishes, with
      the ability to cure under ultraviolet (UV) radiation, and consequently
      demonstrate improved properties and greater durability compared to conventional
      nail polishes. Most gel nail polishes available today are based on petrochemical
      resources, making them unsustainable. Bio-based materials are excellent renewable
      resources, with high potential for meeting final-product performance, cost, and
      environmental needs. In addition, bio-based materials can be modified to make
      them amenable to being cured by advanced Light Emitting Diode (LED) resources
      that consume low energy and are safer for human exposure compared to conventional
      UV-mercury lamps. Consumer preference for use of products made from bio-based
      sources has been clearly growing. On the other hand, according to the U.S.
      Department of Energy (DOE) technology roadmap, a considerable amount of basic
      chemical building blocks should be derived from plant-based renewable materials
      in near future. However, to the best of our knowledge, bio-based nail products
      have not been sufficiently explored. Therefore, to keep pace with environmental
      regulations and consumer preference, there is an unmet opportunity to develop
      novel, sustainable nail gel polishes with considerable bio-renewable content. In
      this study, two sustainable UV-LED curable gel nail polish prototypes-one high
      solids zero-volatile organic content (VOC) and the other waterborne, both with
      considerable bio-renewable content, were designed. METHODS: Both formulations
      were cured under both UV-mercury and UV-LED radiation sources in order to
      evaluate their curing efficiency under a UV-LED source. Also, their performance
      was compared with a commercial petro-based benchmark. RESULTS: The high-solids
      formulation demonstrated promising performance, exceeding that of the benchmark
      in opacity, chemical properties, gloss, and pendulum hardness, while the
      waterborne formulation met most of the desirable requirements with some
      significant technical benefits, including low odour and higher renewable raw
      material content. CONCLUSION: These novel gel nail polishes are greener
      alternatives to the current products in the market with high potential for
      promising consumer acceptance.

PMID- 30300457
TI  - Multiple sclerosis - a review.
AB  - Multiple sclerosis (MS) is the commonest non-traumatic disabling disease to
      affect young adults. The incidence of MS is increasing worldwide, together with
      the socioeconomic impact of the disease. The underlying cause of MS and
      mechanisms behind this increase remain opaque, although complex gene-environment
      interactions almost certainly play a significant role. The epidemiology of MS
      indicates that low serum levels of vitamin D, smoking, childhood obesity and
      infection with the Epstein-Barr virus are likely to play a role in disease
      development. Changes in diagnostic methods and criteria mean that people with MS
      can be diagnosed increasingly early in their disease trajectory. Alongside this,
      treatments for MS have increased exponentially in number, efficacy and risk.
      There is now the possibility of a diagnosis of 'pre-symptomatic MS' being made;
      as a result potentially preventive strategies could be studied. In this
      comprehensive review, MS epidemiology, potential aetiological factors and
      pathology are discussed, before moving on to clinical aspects of MS diagnosis and
      management.

PMID- 30300458
TI  - High burden of neurological disease in the older general population: results from
      the Canadian Longitudinal Study on Aging.
AB  - BACKGROUND AND PURPOSE: Our objective was to study the association between the
      presence of a neurological disease and the comorbidity burden as well as
      healthcare utilization (HCU). METHODS: Using baseline data from the Canadian
      Longitudinal Study on Aging (CLSA), we examined the burden of five neurological
      conditions. The CLSA is a population-based study of approximately 50 000
      individuals, aged 45-85 years at baseline. We used multivariable Poisson
      regression to identify correlates of comorbidity burden and HCU. RESULTS: The
      lifetime prevalence of five neurological diseases is presented: epilepsy,
      Parkinson's disease/parkinsonism, stroke/transient ischaemic attack, multiple
      sclerosis and migraine. We found the somatic and psychiatric comorbidity burden
      to be higher in those individuals with a neurological disease (an 18-45% mean
      increase in the number of chronic conditions) as compared with the comparison
      group without a neurological disease, except for Parkinson's
      disease/parkinsonism. The presence of a neurological disease was associated with
      only a modest increase in the probability of visiting a general practitioner but
      was associated with a greatly increased probability of visiting a medical
      specialist (up to 68% more likely) or an emergency department (up to 79% more
      likely) and an overnight hospitalization (up to 108% more likely). CONCLUSIONS:
      We found striking associations between our neurological diseases and increased
      comorbidity burdens and HCU. These findings are important for informing public
      policy planning as well as driving avenues for future research. The present study
      established the CLSA as an important research platform for the study of
      neurological conditions in an aging general population.

PMID- 30300459
TI  - CNT Interwoven Nitrogen and Oxygen Dual-Doped Porous Carbon Nanosheets as Free
      Standing Electrodes for High-Performance Na-Se and K-Se Flexible Batteries.
AB  - Na-Se and K-Se batteries are attractive as a stationary energy storage system
      because of much abundant resources of Na and K in the Earth's crust. As the alloy
      type Se has a severe pulverization issue, one critical challenge to develop
      advanced Na-Se and K-Se batteries is to explore a highly efficient and stable Se
      based cathode. Herein, a flexible free-standing Se/carbon composite film is
      prepared by encapsulation of Se into a carbon nanotube (CNT) interwoven N,O dual
      doped porous carbon nanosheet (Se@NOPC-CNT). The 3D interconnected CNT uniformly
      wrapped on the N,O dual-doped porous carbon skeletons improves the flexibility
      and offers an interconnected conductive pathway for rapid ionic/electronic
      transport. In addition, the N,O dual-doping significantly enhances the chemical
      affinity and adhesion between Nax Se/Kx Se (0 < x <= 2) and porous carbon, which
      is confirmed by density functional theory calculation. When used as the cathode
      in Na-Se batteries, the Se@NOPC-CNT delivers a remarkable reversible capacity of
      400 mA h g-1 at 1 A g-1 after 2000 cycles with a 0.008% capacity decay per cycle.
      For K-Se batteries, it also exhibits an excellent cycling stability (335 mA h g-1
      after 700 cycles at 0.8 A g-1 ). This unique design may open an avenue for
      practical application of flexible Na-Se and K-Se batteries.

PMID- 30300460
TI  - The morphogenesis of the renal plexus: Renal artery and sympathetic fibers.
AB  - To examine the origin and development of the renal plexus and its relationship to
      the renal vessels in embryos and early human fetuses. Serial sections of 34 human
      embryos (stages 16 to 23 of Carnegie, 4 or 5-8 weeks) and 38 fetuses (9-19 weeks)
      were analyzed. Throughout the embryonic period, the kidney was not innervated by
      the renal plexus. Those nerves appeared at the beginning of the early fetal
      period (9 weeks) as branches given off by the immature autonomic abdominal
      plexus. The renal nerves started to approach to the kidney during the early fetal
      period at 9-10 weeks of development. They were distributed in close proximity to
      the renal arteries and their branches. They were observed first with the
      settlement of the renal veins. The renal artery is present as a branch of the
      abdominal aorta at stage 19 (between 6 and 7 weeks) prior to development of the
      renal plexus. The renal veins were not present during the embryonic period but
      appeared at the start of the fetal period, along with the renal nerves that
      emerged from segmented sympathetic para-aortic bodies (SPBs). Clin. Anat., 2018.
      (c) 2018 Wiley Periodicals, Inc.

PMID- 30300461
TI  - Melphalan-based autologous transplant in octogenarian multiple myeloma patients.

PMID- 30300462
TI  - Adiponectin profile at baseline is correlated to progression and severity of
      multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Adiponectin is a cytokine linking energy metabolism and
      immune system. After being assembled, adiponectin circulates as oligomers of
      different molecular weight, i.e. low, medium and high (HMW) molecular weight.
      These have the most potent biological effects. Multiple sclerosis (MS) is an
      autoimmune disease of the human central nervous system. The aim of this study was
      to characterize the expression levels of both total adiponectin and its
      oligomerization state in the serum from 99 patients with MS at baseline (i.e. not
      influenced by therapies). We also investigated the potential relationships
      between adiponectin and disease progression and severity. METHODS: Adiponectin
      was quantified and visualized by enzyme-linked immunosorbent assay, western
      blotting and fast protein liquid chromatography. During the follow-up (3.6 +/-
      2.20 years), the patients were evaluated using total annualized relapse rate and
      Expanded Disability Status Scale score. RESULTS: Total adiponectin is
      statistically higher in patients with MS compared with matched controls (12.18
      vs. 10.02 MUg/mL, P = 0.001). Interestingly, the adiponectin oligomerization
      state is altered in MS, with an increase of HMW oligomers. In addition, patients
      with MS with higher levels of adiponectin at baseline have significantly higher
      risk of progression and severity (Multiple Sclerosis Severity Score, 3.84 vs.
      2.44, P = 0.001). No statistical difference in adiponectin expression was found
      between active and inactive patients with MS and among the different forms of
      disease. CONCLUSIONS: This study demonstrated that adiponectin and its HMW
      oligomers are greatly involved in MS autoimmune disorder representing a potential
      biomarker to predict worse MS prognosis and severity. Further studies are
      required to clarify the molecular mechanisms underlying the properties of
      adiponectin and HMW oligomers in MS.

PMID- 30300466
TI  - Quantitative Analysis of Food Science Trends.

PMID- 30300463
TI  - Management of psychogenic non-epileptic seizures: a multidisciplinary approach.
AB  - The International League against Epilepsy (ILAE) proposed a diagnostic scheme for
      psychogenic non-epileptic seizure (PNES). The debate on ethical aspects of the
      diagnostic procedures is ongoing, the treatment is not standardized and
      management might differ according to age group. The objective was to reach an
      expert and stakeholder consensus on PNES management. A board comprising adult and
      child neurologists, neuropsychologists, psychiatrists, pharmacologists, experts
      in forensic medicine and bioethics as well as patients' representatives was
      formed. The board chose five main topics regarding PNES: diagnosis; ethical
      issues; psychiatric comorbidities; psychological treatment; and pharmacological
      treatment. After a systematic review of the literature, the board met in a
      consensus conference in Catanzaro (Italy). Further consultations using a model of
      Delphi panel were held. The global level of evidence for all topics was low. Even
      though most questions were formulated separately for children/adolescents and
      adults, no major age-related differences emerged. The board established that the
      approach to PNES diagnosis should comply with ILAE recommendations. Seizure
      induction was considered ethical, preferring the least invasive techniques. The
      board recommended looking carefully for mood disturbances, personality disorders
      and psychic trauma in persons with PNES and considering cognitive-behavioural
      therapy as a first-line psychological approach and pharmacological treatment to
      manage comorbid conditions, namely anxiety and depression. Psychogenic non
      epileptic seizure management should be multidisciplinary. High-quality long-term
      studies are needed to standardize PNES management.

PMID- 30300464
TI  - Evaluation of Nutritional Compositions, Bioactive Compounds, and Antioxidant
      Activities of Shanxi Aged Vinegars During the Aging Process.
AB  - : Shanxi aged vinegar (SAV) is known as famous fermented food in China. During
      the brewing process, a large number of nutritional substances and bioactive
      compounds are produced, which have beneficial effects on human body. In this
      study, the contents of nutritional compositions including proteins, fats,
      carbohydrates, organic acids, and amino acids were determined in SAV samples. The
      antioxidant compounds and properties of SAV with different aging time were also
      evaluated. The results showed that the contents of proteins, crude fats, and
      carbohydrates in SAV were not changed with the aging time. Moreover, Alanine was
      the main component of amino acids in SAV, and the total contents of amino acids
      were increased with the aging time. Acetic acid and lactic acid were the
      predominant organic acids in SAV. The contents of acetic acid and lactic acid
      accounted for more than 90% of the total organic acids in SAV, which were
      increased during the aging process of 5 years. Furthermore, total phenols,
      flavonoids contents, and browning index in SAV were also increased during the
      aging time. These antioxidant compounds showed a high correlation with the
      antioxidant activities of SAV measured by ferric reducing antioxidant power and
      2,2'-azino-bis(3-ethylbenzthi azoline-6-sulfonic acid) assays. The contribution
      of polyphenolic fractions and high molecular weight melanoidins to total
      antioxidant activities was similar (about 49% and 48%, respectively). Our
      findings would provide new insights to further explore the development of new
      vinegar-based functional foods. PRACTICAL APPLICATION: The analysis of
      nutritional compositions, bioactive compounds, and antioxidant capacities in
      vinegars provides a theoretical basis for the function of SAV. It also provides
      references for further explore the development of new-type functional and healthy
      vinegars.

PMID- 30300467
TI  - Meat Color Stability of Ovine Muscles Is Related to Glycolytic Dehydrogenase
      Activities.
AB  - The relationship between glycolytic dehydrogenase, including glyceraldehyde-3
      phosphate dehydrogenase (GAPDH), lactic dehydrogenase (LDH), and meat color
      stability was studied in this study using ovine muscle. Three different ovine
      muscles, including M. longissimus lumborum (LL), M. semimembranosus (SM), and M.
      psoas major (PM), were obtained (n = 10, respectively), and then displayed for 7
      days at 4  degrees C. The LL and SM muscle had higher surface redness, higher (P
      < 0.05) GAPDH activity, nicotinamide adenine dinucleotide (NADH) content, and
      lower (P < 0.05) LDH-B activity than PM muscles during display. The PM muscle had
      the worst color stability and lowest NADH content. These results suggest that
      variation in color stability of physiologically different muscles may be affected
      by glycolysis dehydrogenases. Comparatively, our data showed that GAPDH may play
      a more important role than LDH-B to maintain meat color stability.

PMID- 30300468
TI  - Sensory restoration of breast reconstruction - The search for the ideal approach
      continues.
AB  - Contemporary reconstructive modalities focus on breast anatomy and attempt to
      reconstruct breasts that are soft, of adequate shape, size, and symmetry.
      However, a functional component, i.e. sensation, has largely been ignored. Flap
      neurotization addresses this shortcoming. While we are still in search of the
      ideal surgical technique to achieve this goal, a novel approach that limits nerve
      harvest to the sensory branch only, thus, minimizing abdominal donor-site
      morbidity, is presented.

PMID- 30300470
TI  - Identification and characterization of vaccine candidates against Hyalomma
      anatolicum-Vector of Crimean-Congo haemorrhagic fever virus.
AB  - Crimean-Congo haemorrhagic fever (CCHF) is a tick borne viral disease reported
      from different parts of the world. The distribution of the CCHF cases are linked
      with the distribution of the principal vector, Hyalomma anatolicum in the
      ecosystem. Presently, vector control is mainly dependent on repeated application
      of acaricides, results in partial efficacy and generated acaricide resistant tick
      strains. Amongst the different components of integrated management programme,
      immunization of hosts is considered as one of the sustainable component. To
      restrict CCHF virus spreading, use of anti-Hyalomma vaccines appears as a viable
      solution. Accordingly, present study was under taken to characterize and evaluate
      vaccine potential of two conserved molecules, ferritin2 (FER2) and tropomyosin
      (TPM). Silencing of the genes conferred a cumulative reduction (rejection +
      unable to engorge) of 61.3% in FER2 and 70.2% in TPM respectively. Furthermore,
      44.2% and 72.7% reduction in engorgement weight, 63.6% and 94.9% reduction in egg
      masses in FER2 and TPM silenced ticks in comparison to LUC-control group was
      recorded. The recombinant protein, rHaFER2 was characterized as 35 kDa protein
      with pI of 5.84 and possesses iron binding domains. While rHaTPM is a 51kDa
      protein with pI of 4.94 having calcium binding domains. Immunization of cross
      bred calves by rHaFER2 conferred 51.7% and 51.2% protection against larvae and
      adults of H. anatolicum challenge infestations. While rHaTPM conferred 63.7% and
      66.4% protection against larvae and adults infestations, respectively. The
      results were comparable with the data generated by RNAi and it clearly showed the
      possibility for the development of anti-hyalomma vaccine to manage CCHF virus and
      Theileria annulata infection in human and animals.

PMID- 30300469
TI  - Soft, Skin-Interfaced Microfluidic Systems with Wireless, Battery-Free
      Electronics for Digital, Real-Time Tracking of Sweat Loss and Electrolyte
      Composition.
AB  - Sweat excretion is a dynamic physiological process that varies with body
      position, activity level, environmental factors, and health status. Conventional
      means for measuring the properties of sweat yield accurate results but their
      requirements for sampling and analytics do not allow for use in the field.
      Emerging wearable devices offer significant advantages over existing approaches,
      but each has significant drawbacks associated with bulk and weight, inability to
      quantify volumetric sweat rate and loss, robustness, and/or inadequate accuracy
      in biochemical analysis. This paper presents a thin, miniaturized, skin
      interfaced microfluidic technology that includes a reusable, battery-free
      electronics module for measuring sweat conductivity and rate in real-time using
      wireless power from and data communication to electronic devices with
      capabilities in near field communications (NFC), including most smartphones. The
      platform exploits ultrathin electrodes integrated within a collection of
      microchannels as interfaces to circuits that leverage NFC protocols. The
      resulting capabilities are complementary to those of previously reported
      colorimetric strategies. Systematic studies of these combined
      microfluidic/electronic systems, accurate correlations of measurements performed
      with them to those of laboratory standard instrumentation, and field tests on
      human subjects exercising and at rest establish the key operational features and
      their utility in sweat analytics.

PMID- 30300471
TI  - Antidiabetic Effect of Abextide, a Long-Acting Exendin-4 Analogue in Cynomolgus
      Monkeys.
AB  - Abextide, synthesized by conjugating an albumin-binding moiety-truncated Evans
      blue-to glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4, shows
      extended drug release and enhanced hypoglycemic effect in diabetic mice. The aim
      of this study is to evaluate the pharmacodynamics of Abextide in nonhuman
      primates. Two batches of elderly cynomolgus monkeys with naturally occurring
      diabetes are used for this study. During the whole experiment period, no
      abnormalities such as swelling at the injection site, lethargy, or hypoglycemia
      are observed in all animals. The monkeys in the Abextide group lose appetite
      after drug administration and then recover over time. In the single dose
      treatment, at day 1 and day 3 after treatment, decreased plasma glucose level is
      observed in the Abextide-treated group but not in placebo or Albiglutide-treated
      group. For monkeys that receive two doses of drug, the blood glucose level in all
      subjects in Abextide group decreases rapidly upon drug administration and return
      to a plateau by day 3. A similar pattern of response is seen after the second
      dose administration. The delayed drug release and hypoglycemic effect of Abextide
      make it potentially useful as an antidiabetic drug for weekly subcutaneous
      administration.

PMID- 30300472
TI  - Discordance in risk factors for the progression of diabetic retinopathy and
      diabetic nephropathy in patients with type 2 diabetes mellitus.
AB  - AIMS/INTRODUCTION: We aimed to investigate whether there are differences in the
      risk factors or markers for the progression of diabetic retinopathy (DR) and
      diabetic nephropathy (DN) in type 2 diabetes mellitus. MATERIALS AND METHODS: We
      carried out a 3-year retrospective cohort study of 604 patients with type 2
      diabetes mellitus. The outcomes were the progression of DR (worsening of the DR
      stage) and DN (an estimated glomerular filtration rate decline >12%) at the 3
      year follow up. The mean hemoglobin A1c (HbA1c) level and HbA1c variability
      (HbA1c-VAR) were calculated. RESULTS: The mean HbA1c and HbA1c-VAR levels were
      higher in the DR progressors (n = 67) than in the DR non-progressors (n = 537).
      The mean HbA1c was a significant predictor for DR progression independent of the
      duration of diabetes and HbA1c-VAR levels. The urine albumin-to-creatinine ratio
      at baseline and HbA1c-VAR levels were higher in the DN progressors (n = 34) than
      in the DN non-progressors (n = 570). The triglyceride to high-density lipoprotein
      cholesterol ratio at baseline tended to be higher in the DN progressors than in
      the DN non-progressors. HbA1c-VAR levels and the triglyceride-to-high-density
      lipoprotein cholesterol ratio were significant predictors for DN progression
      independent of estimated glomerular filtration rate and the urine albumin-to
      creatinine ratio. CONCLUSIONS: Average glycemia was significantly associated with
      progression of DR, whereas glycemic variability and dyslipidemia were
      significantly associated with progression of DN in type 2 diabetes mellitus.

PMID- 30300473
TI  - One-Step Synthesis of Iodinated Polypyrrole Nanoparticles for CT Imaging Guided
      Photothermal Therapy of Tumors.
AB  - Theranostic materials are of great significance to a personalized precise
      medicine. However, conventional theranostic agents are mainly fabricated by
      combining presynthesized independent imaging probes and therapeutic agents,
      suffering from multiple synthesis procedures, poor morphological control, and
      time/reagent-consuming process. Herein, iodinated polypyrrole (I-PPy)
      nanoparticles are fabricated via a one-step synthesis strategy combining chemical
      oxidation and iodination for computed tomography (CT) imaging-guided photothermal
      therapy. Iodic acid with a high standard electrode potential enables the chemical
      oxidation polymerization of pyrrole monomers. Meanwhile, the iodination of PPy
      induced by the corresponding reduction product I2 takes place during the
      polymerization process to generate I-PPy nanoparticles. The prepared I-PPy
      nanoparticles possess a uniform size, excellent colloidal stability, intense near
      infrared absorption, strong X-ray attenuation ability, and favorable
      biocompatibility. The as-synthesized I-PPy nanoparticles not only guarantee
      remarkable contrast-enhanced CT imaging of blood pool and tumors, but also
      realize effective tumor suppression in vitro and in vivo by I-PPy nanoparticles
      mediated CT imaging-guided photothermal therapy. To the best of the authors'
      knowledge, it is the first time that multifunctional PPy nanoparticles are
      fabricated through a one-step synthesis process. The proposed strategy opens up a
      new way for the fabrication of high-performance theranostic agents via a one-step
      strategy under mild conditions.

PMID- 30300474
TI  - The association of childhood sleep problems with the prevalence of traumatic
      dental injury in schoolchildren.
AB  - BACKGROUND/AIM: Sleep quality exerts an influence on attention level and motor
      skills and is associated with accidental injuries in children. The aim of this
      study was to evaluate the association between traumatic dental injury and sleep
      behaviour in children. MATERIAL AND METHODS: A cross-sectional study was
      conducted in a small city in southern Brazil with a representative sample of
      schoolchildren aged 8-10 years (n = 537). Weight and height were measured, and
      examinations were performed for the determination of clinical occlusion and
      traumatic dental injury. The parents answered the Sleep Behaviour Questionnaire
      and questions addressing socio-demographic characteristics. RESULTS: The
      prevalence of traumatic dental injury was 22% (95% CI: 19-26) and was higher
      among children who woke three to four times per night (PR = 3.30; 95% CI: 2.47
      4.39), those who fell asleep in the parental bed (PR = 1.41; 95% CI: 1.09-1.83),
      those who were not in a good mood on waking up in the morning (PR = 1.30; 95% CI:
      1.02-1.65), those who became sleepy while sitting and/or studying (PR = 1.57; 95%
      CI: 1.09-2.24) and while watching TV (PR = 1.41; 95% CI: 1.0005-1.97) and those
      who had bad dreams (PR = 1.35; 95% CI: 1.04-1.76). The Poisson multiple
      regression model with a multilevel approach revealed that the prevalence of
      traumatic dental injury was 1.51-fold higher among children with daytime
      drowsiness (PR = 1.51; 95% CI: 1.11-2.04) after adjusting for socio-demographic,
      occlusal and anthropometric variables. CONCLUSION: Sleep problems were associated
      with a higher prevalence of traumatic dental injury among the children analysed.

PMID- 30300475
TI  - Thermoforming method to effectively maintain mouthguard thickness: Effect of
      moving the model position just before vacuum formation.
AB  - BACKGROUND/AIMS: Mouthguards can reduce the risk of sports-related injuries but
      the sheet material and thickness have a large effect on their efficacy and
      safety. The aim of this study was to investigate the effect of the thermoforming
      technique that moves the model position just before vacuum formation. MATERIALS
      AND METHODS: Ethylene vinyl acetate sheets of 4.0-mm thickness and a vacuum
      forming machine were used. The working model was placed with its anterior rim
      positioned 40 mm from the front of the forming table. Three forming conditions
      were compared: (a) The sheet was formed when it sagged 15 mm at the top of the
      post under normal conditions (control); (b) the sheet frame was lowered to and
      heated at 50 mm from the level of ordinary use, and the sheet was formed when it
      sagged 15 mm (LH); and (c) the sheet frame at the top of the post was lowered and
      covered on the model when it sagged 15 mm. Subsequently, the rear side of the
      model was pushed to move it forward 20 mm, and it was then formed (MP). Sheet
      thickness after fabrication was determined for the incisal edge, labial surface,
      and buccal surface using a specialized caliper accurate to 0.1 mm. Thickness
      differences among forming conditions were analyzed by one-way ANOVA and
      Bonferroni's multiple comparison tests. RESULTS: A significant difference was
      observed for all measurement points, and the thickness after formation increased
      in the order of control, LH, and MP. Particularly on the labial surface, MP was
      able to yield about 1.7 times the thickness (about 3.1 mm) of the control.
      CONCLUSION: The forming method of moving the model forward just before vacuum
      formation was effective for suppressing the mouthguard thickness reduction, which
      is capable of securing the labial thickness at 3 mm or more with a single layer.

PMID- 30300476
TI  - Review of the role of cigarette smoking in diabetic foot.
AB  - Diabetic foot ulceration has been a serious issue over the past decades in Asia,
      causing economic and social problems. Therefore, it is important to identify and
      reduce the risk factors of diabetic foot. Cigarette smoking has been reported to
      be associated with diabetes and its macrovascular complications, but the
      relationship between smoking and diabetic foot ulcers is still unclear. In the
      present review, we summarize the effects of cigarette smoking on diabetic foot
      ulcers with respect to peripheral neuropathy, vascular alterations and wound
      healing. One underlying mechanism of these impacts might be the smoking-induced
      oxidative stress inside the cells. At the end of this review, the current
      mainstream therapies for smoking cessation are also outlined. We believe that it
      is urgent for all diabetic patients to quit smoking so as to reduce their chances
      of developing foot ulcers and to improve the prognosis of diabetic foot ulcers.

PMID- 30300477
TI  - Verzogerte bullose Druckurtikaria: die verwirrende Rolle der eosinophilen
      Granulozyten.

PMID- 30300478
TI  - Dermatologische Aspekte aus der S2k-Leitlinie zum Down-Syndrom im Kindes- und
      Jugendalter.
AB  - Das Down-Syndrom (DS) ist mit einer Inzidenz von 1 : 700 aller Geburten nicht
      selten und mit diversen Erkrankungen unterschiedlicher Organsysteme assoziiert.
      Zu den schwerwiegenden Erkrankungen zahlen Herzfehler und Leukamie. Letztere
      zeigt sich im Neugeborenenalter und geht nicht immer in eine klassische
      myeloische Leukamie uber (transiente myeloproliferative Erkrankung).
      Dermatologisch bilden die Neugeborenen Pusteln/Vesikulopusteln, die bei DS nicht
      nur an typische Neugeborenenexantheme und Infektionen, sondern auch an die
      transiente myeloproliferative Erkrankung denken lassen sollten. Die meisten
      Dermatosen jedoch sind benigner Natur und umfassen im Wesentlichen
      Verhornungsstorungen, die sich als Xerosis, Keratosis pilaris, Lichenifikation
      und Ichthyosis vulgaris zeigen. Typisch, aber nicht spezifisch, ist auch die
      palmare Vierfingerfurche. Die Patienten neigen haufig zu Follikulitiden, die
      aufgrund einer Elastolyse in eine Anetodermie ubergehen. Die bekannte
      Immundysbalance erklart das Auftreten von Autoimmunerkrankungen, die sich an der
      Haut als Alopecia areata und Vitiligo manifestieren. Als typische
      Hautveranderungen bei DS zahlen zudem Elastosis perforans serpiginosa, Syringome,
      Milien-ahnliche Calcinosis cutis (Milia-like calcinosis cutis) und Multiple
      eruptive Dermatofibrome.

PMID- 30300479
TI  - Rasch wachsende verrukose axillare Tumoren, multiple Erosionen, Pusteln und
      Cheilitis.

PMID- 30300480
TI  - Plaques und Tumoren unter der Therapie mit Mogamulizumab bei einer Patientin mit
      refraktarem Sezary-Syndrom.

PMID- 30300481
TI  - Delayed bullous pressure urticaria: the puzzling role of eosinophils.

PMID- 30300482
TI  - Bienen- und Wespengiftallergie: Sensibilisierung und spezifische Immuntherapie.

PMID- 30300483
TI  - Adulte Akne (Acne tarda) der Frau: Eine Herausforderung fur den Dermatologen.

PMID- 30300484
TI  - Ein Fall von Muckle-Wells-Syndrom mit einer neuen NLRP3-Mutation.

PMID- 30300485
TI  - Muscle hypertrophy and onychodystrophy.

PMID- 30300486
TI  - Die histologische intralasionale Heterogenitat aktinischer Keratosen als Zeichen
      von Feldkanzerisierung.

PMID- 30300487
TI  - Mehrere livid-erythematose Maculae und Plaques mit leichter Abschuppung bei einem
      jungen Mann.

PMID- 30300488
TI  - OGDV Preistrager stellen sich vor: Der MEDA Non Melanoma Skin Cancer
      Forschungspreis 2017 ging an Mag. rer. nat. Bettina Huber, PhD, aus Wien.

PMID- 30300489
TI  - Cryopyrin-assoziiertes periodisches Syndrom (CAPS) bei T348M-Mutation im NLRP3
      Gen.

PMID- 30300490
TI  - Ein nicht heilender Herpes zoster ophthalmicus.

PMID- 30300491
TI  - Dermatological aspects of the S2k guidelines on Down syndrome in childhood and
      adolescence.
AB  - With an incidence of 1 in 700 births, Down syndrome (DS) is not an uncommon
      condition. It is associated with various disorders of different organ systems.
      Serious disorders include cardiac defects and leukemia. With an onset during the
      newborn period, the latter does not always progress to classic myeloid leukemia
      (transient myeloproliferative disorder). Skin manifestations in newborns include
      pustules/vesiculopustules. In individuals with DS, such lesions should not only
      prompt suspicion for typical neonatal rashes and infections but also for
      transient myeloproliferative disorder. However, most dermatoses are benign. They
      essentially comprise disorders of keratinization that present as xerosis,
      keratosis pilaris, lichenification, and ichthyosis vulgaris. Also typical but not
      specific is the four-finger palmar crease (simian crease). Patients frequently
      develop folliculitides, which - due to elastolysis - subsequently progress to
      anetoderma. The known immune disturbance in DS patients explains the occurrence
      of autoimmune diseases such as alopecia areata and vitiligo. Typical skin
      conditions associated with DS include elastosis perforans serpiginosa,
      syringomas, milia-like calcinosis cutis, and multiple eruptive dermatofibromas.

PMID- 30300492
TI  - Perifolliculitis capitis abscedens et suffodiens: eine Fallserie mit 66 Patienten
      und ein Vorschlag zur Klassifikation.

PMID- 30300493
TI  - AIDS-assoziierte disseminierte Talaromyces marneffei-Mykose (vormals Penicillium
      marneffei-Mykose).

PMID- 30300494
TI  - Muskelhypertrophie und Onychodystrophie.

PMID- 30300495
TI  - Eruptive Hypomelanose - der erste Fall aubetaerhalb Asiens.

PMID- 30300496
TI  - Kongresskalender 2018.

PMID- 30300497
TI  - Wirksamkeit einer ablationsbasierten Kombinationstherapie bei Vitiligo: Eine
      systematische Ubersichtsarbeit und Metaanalyse.

PMID- 30300498
TI  - Langzeitergebnisse nach Schweibetadrusenresektion bei axillarer Hyperhidrose.

PMID- 30300499
TI  - Honeybee and wasp venom allergy: Sensitization and immunotherapy.
AB  - Hymenoptera venom allergy is the most common cause of anaphylactic reactions in
      adults. In children, it is the second most common cause after food-related
      anaphylaxis. Such reactions are primarily due to stings by honeybees (Apis) and
      certain social wasps (Vespula vulgaris and Vespula germanica in particular).
      Especially in adults, stings are frequently associated with severe anaphylaxis.
      Established diagnostic methods including molecular tests allow for greater
      success rates in terms of determining the insect actually responsible for
      triggering the anaphylactic reaction. Sensitization to both venoms, or a history
      of systemic sting reaction without any evidence of sensitization, complicate the
      decision regarding treatment. Venom immunotherapy (VIT) is a safe and effective
      causal treatment.

PMID- 30300501
TI  - An Early History of Medical Translation.

PMID- 30300500
TI  - Akne bei erwachsenen Frauen: Physiologische und psychologische Erwagungen und
      Management.

PMID- 30300503
TI  - High Electrical Conductivity 2D MXene Serves as Additive of Perovskite for
      Efficient Solar Cells.
AB  - MXenes, a newly intriguing family of 2D materials, have recently attracted
      considerable attention owing to their excellent properties such as high
      electrical conductivity and mobility, tunable structure, and termination groups.
      Here, the Ti3 C2 Tx MXene is incorporated into the perovskite absorber layer for
      the first time, which aims for efficiency enhancement. Results show that the
      termination groups of Ti3 C2 Tx can retard the crystallization rate, thereby
      increasing the crystal size of CH3 NH3 PbI3 . It is found that the high
      electrical conductivity and mobility of MXene can accelerate the charge transfer.
      After optimizing the key parameters, 12% enhancement in device performance is
      achieved by 0.03 wt% amount of MXene additive. This work unlocks opportunities
      for the use of MXene as potential materials in perovskite solar cell
      applications.

PMID- 30300504
TI  - Biochemical characterization of the minimal domains of an iterative eukaryotic
      polyketide synthase.
AB  - Iterative type I polyketide synthases (PKS) are megaenzymes essential to the
      biosynthesis of an enormously diverse array of bioactive natural products. Each
      PKS contains minimally three functional domains, beta-ketosynthase (KS),
      acyltransferase (AT), and acyl carrier protein (ACP), and a subset of reducing
      domains such as ketoreductase (KR), dehydratase (DH), and enoylreductase (ER).
      The substrate selection, condensation reactions, and beta-keto processing of the
      polyketide growing chain are highly controlled in a programmed manner. However,
      the structural features and mechanistic rules that orchestrate the iterative
      cycles, processing domains functionality, and chain termination in this kind of
      megaenzymes are often poorly understood. Here, we present a biochemical and
      functional characterization of the KS and the AT domains of a PKS from the
      mallard duck Anas platyrhynchos (ApPKS). ApPKS belongs to an animal PKS family
      phylogenetically more related to bacterial PKS than to metazoan fatty acid
      synthases. Through the dissection of the ApPKS enzyme into mono- to didomain
      fragments and its reconstitution in vitro, we determined its substrate
      specificity toward different starters and extender units. ApPKS AT domain can
      effectively transfer acetyl-CoA and malonyl-CoA to the ApPKS ACP stand-alone
      domain. Furthermore, the KS and KR domains, in the presence of Escherichia coli
      ACP, acetyl-CoA, and malonyl-CoA, showed the ability to catalyze the chain
      elongation and the beta-keto reduction steps necessary to yield a 3
      hydroxybutyryl-ACP derivate. These results provide new insights into the
      catalytic efficiency and specificity of this uncharacterized family of PKSs.

PMID- 30300505
TI  - Molecular recognition of the beta-glucans laminarin and pustulan by a SusD-like
      glycan-binding protein of a marine Bacteroidetes.
AB  - Marine bacteria catabolize carbohydrate polymers of algae, which synthesize these
      structurally diverse molecules in ocean surface waters. Although algal glycans
      are an abundant carbon and energy source in the ocean, the molecular details that
      enable specific recognition between algal glycans and bacterial degraders remain
      largely unknown. Here we characterized a surface protein, GMSusD from the
      planktonic Bacteroidetes-Gramella sp. MAR_2010_102 that thrives during algal
      blooms. Our biochemical and structural analyses show that GMSusD binds glucose
      polysaccharides such as branched laminarin and linear pustulan. The 1.8 A crystal
      structure of GMSusD indicates that three tryptophan residues form the putative
      glycan-binding site. Mutagenesis studies confirmed that these residues are
      crucial for laminarin recognition. We queried metagenomes of global surface water
      datasets for the occurrence of SusD-like proteins and found sequences with the
      three structurally conserved residues in different locations in the ocean. The
      molecular selectivity of GMSusD underscores that specific interactions are
      required for laminarin recognition. In conclusion, our findings provide insight
      into the molecular details of beta-glucan binding by GMSusD and our bioinformatic
      analysis reveals that this molecular interaction may contribute to glucan cycling
      in the surface ocean.

PMID- 30300506
TI  - Big Data - big chance, big challenge.

PMID- 30300507
TI  - [in process].

PMID- 30300508
TI  - [in process].

PMID- 30300509
TI  - [in process].

PMID- 30300510
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PMID- 30300511
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PMID- 30300512
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PMID- 30300513
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PMID- 30300515
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PMID- 30300514
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PMID- 30300516
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PMID- 30300518
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PMID- 30300517
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PMID- 30300519
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PMID- 30300520
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PMID- 30300521
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PMID- 30300523
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PMID- 30300522
TI  - [in process].

PMID- 30300525
TI  - [in process].

PMID- 30300524
TI  - [in process].

PMID- 30300527
TI  - Big Data, better care?.

PMID- 30300526
TI  - [in process].

PMID- 30300528
TI  - [in process].

PMID- 30300529
TI  - [in process].

PMID- 30300530
TI  - [in process].

PMID- 30300531
TI  - [in process].

PMID- 30300532
TI  - The effect of surgery on fat mass, lipid and glucose metabolism in mild primary
      hyperparathyroidism
AB  - Context: Mild primary hyperparathyroidism has been associated with increased body
      fat mass and unfavorable cardiovascular risk factors. Objective: To assess the
      effect of parathyroidectomy on fat mass, glucose and lipid metabolism. Design,
      patients, interventions, main outcome measures: 119 patients previously
      randomized to observation (OBS; n = 58) or parathyroidectomy (PTX; n = 61) within
      the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, an
      open randomized multicenter study, were included. Main outcome measures for this
      study were the differences in fat mass, markers for lipid and glucose metabolism
      between OBS and PTX 5 years after randomization. Results: In the OBS group, total
      cholesterol (Total-C) decreased from mean 5.9 (+/-1.1) to 5.6 (+/-1.0) mmol/L (P
      = 0.037) and LDL cholesterol (LDL-C) decreased from 3.7 (+/-1.0) to 3.3 (+/-0.9)
      mmol/L (P = 0.010). In the PTX group, the Total-C and LDL-C remained unchanged
      resulting in a significant between-group difference over time (P = 0.013 and P =
      0.026, respectively). This difference was driven by patients who started with
      lipid-lowering medication during the study period (OBS: 5; PTX: 1). There was an
      increase in trunk fat mass in the OBS group, but no between-group differences
      over time. Mean 25(OH) vitamin D increased in the PTX group (P < 0.001), but did
      not change in the OBS group. No difference in parameters of glucose metabolism
      was detected. Conclusion: In mild PHPT, the measured metabolic and cardiovascular
      risk factors were not modified by PTX. Observation seems safe and cardiovascular
      risk reduction should not be regarded as a separate indication for
      parathyroidectomy based on the results from this study.

PMID- 30300534
TI  - Adherence and long-term growth outcomes: results from the easypodTM connect
      observational study (ECOS) in paediatric patients with growth disorders
AB  - Objective: The easypod connect observational study (ECOS) assessed treatment
      adherence among paediatric patients receiving growth hormone (GH) via the easypod
      electronic injection device. Design: ECOS was an open-label, observational,
      longitudinal study conducted in 24 countries between 2010 and 2016, enrolling
      children treated with GH. Methods: The primary endpoint was the rate of treatment
      adherence during 5 years of follow-up. Impact of adherence on growth outcomes was
      assessed using Spearman's product-moment correlations. Results and conclusions:
      Overall, 1190 patients had easypod data available for >=3 months; most patients
      had GH deficiency (75%); 606 of these patients were GH naive at baseline. Over
      the first year of monitoring, the median rate of adherence was 93.7% among
      patients overall and >93.0% in GH-naive patients, irrespective of the treatment
      indication. Clinically meaningful improvements in growth rates were observed
      after 1 year of treatment across all GH indications. Adherence decreased with
      increasing treatment duration, but the overall median adherence rate remained
      high after 3 years of follow-up: 87.2% (n = 409), 75.5% after 4 years (n = 143)
      and 70.2% after 5 years (n = 43). Statistically significant correlations between
      adherence and 1-year change in height standard deviation score (P < 0.001 for
      patients overall) and height velocity (P < 0.001) were observed. Conclusions:
      ECOS produced accurate, real-time adherence data in a large population of GH
      treated children over 5 years of follow-up. Using the easypod connect system,
      physicians can potentially identify patients with inadequate adherence and poor
      response to treatment, enabling them to take appropriate action to help them
      maximise the benefits of GH treatment.

PMID- 30300533
TI  - Post-chemotherapy serum anti-Mullerian hormone level predicts ovarian function
      recovery
AB  - In the era of precision medicine, the prediction of ovarian function recovery
      from chemotherapy-induced amenorrhoea using feasible biological markers may be
      helpful to optimise the treatment strategy for young patients with hormone
      receptor-positive breast cancer. The purpose of this study was to investigate the
      accuracy of post-chemotherapy biological markers for predicting the recovery of
      ovarian function in breast cancer patients of the ASTRRA trial, with chemotherapy
      induced amenorrhoea. Using data of 82 participants from a single institution in
      the ASTRRA trial, the post-chemotherapy serum levels of the anti-Mullerian
      hormone (AMH), oestradiol, inhibin B and other clinical factors associated with
      chemotherapy-induced amenorrhoea were evaluated. Recovery of ovarian function was
      defined by the resumption of menstruation manifested by vaginal bleeding. Fifty
      two patients regained menstruation within 55 months after enrolment. In
      univariate analysis, <40 years of age (P = 0.009), oestradiol >=37 pg/mL (P =
      0.003) or AMH >=800 pg/mL (P = 0.026) were associated with recovery of
      menstruation. On multivariate analysis, oestradiol (hazard ratio: 3.171, 95% CI:
      1.306-7.699, P = 0.011) and AMH (hazard ratio: 2.853, 95% CI: 1.011-8.046, P =
      0.048) remained as significant independent predictors for resumption of
      menstruation. The diagnostic accuracy of age, oestradiol and AMH in predicting
      the resumption of menstruation was 38.3, 23.3 and 86.7%, respectively. In
      conclusion, post-chemotherapy AMH level might be a relatively accurate predictor
      of the recovery of ovarian function, presented by resumption of menstruation in
      breast cancer patients with chemotherapy-induced amenorrhoea

PMID- 30300535
TI  - Behavioural phenotyping, learning and memory in young and aged growth hormone
      releasing hormone-knockout mice
AB  - Background: Growth hormone-releasing hormone (GHRH) plays an important role in
      brain functions. The aim of this study was to examine cognitive functions and
      emotional behaviour in a mouse model of isolated GH deficiency due to bi-allelic
      ablation of the GHRH gene (GHRH knockout, GHRHKO). Methods: Learning, memory and
      emotional behaviour were evaluated using a series of validated tests (Morris
      water maze, eight-arm radial maze, open field, elevated plus maze test, forced
      swim tests) in 2-, 5- and 12-month-old male mice either homozygous (-/-) or
      heterozygous (+/-) for the GHRHKO allele. Results: Compared with age-matched +/-
      mice, -/- mice showed decreased cognitive performance in Morris water maze and
      eight-arm radial maze tests. By comparing the effects of aging in each genotype,
      we observed an age-related impairment in test results in +/- mice, while in -/-
      mice a significant decline in cognitive function was found only in 12 months
      compared with 2-month-old mice, but no difference was found between 5 months old
      vs 2 months old. -/- mice showed increased exploration activity compared to age
      matched +/- controls, while both strains of mice had an age-related decrease in
      exploration activity. When evaluated through open field, elevated plus maze and
      forced swim tests, -/- mice demonstrated a decrease in anxiety and depression
      related behaviour compared to age-matched +/- controls. Conclusions: Our results
      suggest that homozygous ablation of GHRH gene is associated with decreased
      performance in learning and memory tests, possibly linked to increased
      spontaneous locomotor activity. In addition, we observed an age-related decline
      in cognitive functions in both genotypes.

PMID- 30300536
TI  - Improved salivary cortisol rhythm with dual-release hydrocortisone
AB  - Introduction and Aim: The purpose of replacement therapy in adrenal insufficiency
      (AI) is mimicking endogenous cortisol levels as closely as possible: dual release
      hydrocortisone (DR-HC) has been introduced to replicate the circadian cortisol
      rhythm. Multiple daily saliva collections could be used to assess the cortisol
      rhythm during real life: our aim was to study the salivary cortisol profile in
      AI. Materials and Methods: We prospectively evaluated, in an observational study,
      18 adult outpatients with AI (11 primary and 7 secondary AI), switched from
      conventional treatment (conv-HC, 25 mg/day) to the same dose of DR-HC. We
      collected six samples of saliva in a day, measuring cortisol (F) and cortisone
      (E) with LC-MS/MS. Forty-three matched healthy subjects served as controls.
      Results: F levels were similar in the morning (and higher than controls) in
      patients treated with conv-HC or DR-HC; otherwise F levels and exposure were
      lower in the afternoon and evening in patients with DR-HC, achieving a cortisol
      profile closer to healthy controls. Daily cortisol exposure, measured with area
      under the curve, was lower with DR-HC. Morning F and E presented sensitivity and
      specificity >90% to diagnose AI (respectively threshold of 3 and 9.45 nmol/L).
      Total cholesterol and HbA1c levels reduced with DR-HC. Conclusions: Salivary
      cortisol daily curve could be used as a new tool to assess the cortisol profiles
      in patients treated with conv-HC and DR-HC. A lower daily cortisol exposure was
      achieved with DR-HC (despite the same HC dose), especially in the afternoon
      evening.

PMID- 30300537
TI  - Circulating MIR148A associates with sensitivity to adiponectin levels in human
      metabolic surgery for weight loss
AB  - Objective: We sought to discover secreted biomarkers to monitor the recovery of
      physiological adiponectin levels with metabolic surgery, focusing on epigenetic
      changes that might predict adiponectin function. Design: We conducted a
      prospective observational study of patients undergoing metabolic surgery by Roux
      en-Y Gastric Bypass (RYGB) for weight loss in a single center (IRB GHS # 1207
      27). Methods: All patients (n = 33; 27 females; 6 males) signed informed consent.
      Metabolites, adiponectin and MIR148A were measured in fasting plasma. We followed
      MIQE for transcript profiles. Results: Patients lost on average 47 +/- 12% excess
      BMI (%EBMI) after 12 weeks. Adiponectin pre, post or delta (post minus pre) did
      not correlate with %EBMIL. A decrease in adiponectin following weight loss
      surgery was observed in a subset of patients, chi-square test of independence
      rejects the null hypotheses that the liver DNA methyltransferase 1 (DNMT1) and
      delta adiponectin are independent (chi-square statistics chi2 = 6.9205, P =
      0.00852, n = 33), as well as MIR148A and delta adiponectin are independent (chi
      square statistics chi2 = 9.6823, P = 0.00186, n = 33). The presence of plasma
      MIR148A allows identification of patients that appear to be adiponectin
      insensitive at baseline. Conclusion: We combined the presence of plasma MIR148A,
      the concentration of total adiponectin and the expression of DNA
      methyltransferase 1 (DNMT1) in liver biopsy tissue to identify patients with non
      physiological adiponectin. Weight loss and physical activity interventions
      complemented with the new method presented here could serve to monitor the
      physiological levels of adiponectin, thought to be important for long-term weight
      loss maintenance.

PMID- 30300538
TI  - The effect of obesity and dietary habits on oxidative stress in Hashimoto's
      thyroiditis
AB  - Objective: Increased oxidative stress has been described in patients with
      Hashimoto's thyroiditis (HT). The aim of the present study was to investigate
      whether high oxidative stress is further influenced by obesity and dietary habits
      in euthyroid women with HT. Methods: Two hundred eighteen consecutive euthyroid
      women with HT were studied and separated in two groups; 102 with thyroxine
      replacement and 114 without. For the evaluation of oxidative stress, total lipid
      peroxide levels in serum (TOS) were measured and recoded as 'high TOS' vs
      'medium/low TOS'. The type of food and consumption frequency were recorded. Two
      binary variables were considered; normal vs low fruit consumption and daily vs
      sporadic vegetable consumption. Results: 'High TOS' was more frequent in women
      under thyroxine replacement (31.4% vs 14.7%, OR = 2.7, 95% CI: 1.4-5.2). The
      prevalence of 'high TOS' was higher among overweight/obese women compared to
      women with normal BMI (30.4% vs 12.5%, OR = 3.1, 95% CI: 1.5-6.4). Low fruit
      consumption was associated with increased 'high TOS' prevalence (30.6% vs 12.9%,
      OR = 3.0, 95% CI: 1.4-6.2). Sporadic vegetable consumption was associated with
      increased 'high TOS' prevalence compared to daily consumption (29.9% vs 13.5%, OR
      = 2.7, 95% CI: 1.3-5.7). The examined risk factors were independent and additive
      in their effect on TOS. At least three risk factors had to be concomitantly
      present for the likelihood of 'high TOS' to be significantly elevated.
      Conclusions: Oxidative stress is increased in women with HT under thyroxine
      replacement. Nevertheless, normal BMI, daily fruit and vegetable consumption, all
      contribute in maintaining oxidative stress at low levels.

PMID- 30300539
TI  - The RET C611Y mutation causes MEN 2A and associated cutaneous
AB  - Background: Cutaneous lichen amyloidosis (CLA) has been reported in some multiple
      endocrine neoplasia type 2A (MEN 2A) families affected by specific germline RET
      mutations C634F/G/R/W/Y or V804M, as a characteristic of the clinical
      manifestation in 'MEN 2A with CLA', one of four variants of MEN 2A, which was
      strictly located in the scapular region of the upper back. Patient Findings: This
      study reports a large south-eastern Chinese pedigree with 17 individuals carrying
      the MEN 2A-harboring germline C611Y (c.1832G>A) RET mutation by Sanger
      sequencing. One individual presented MEN 2A-related clinical features, including
      typical CLA in the interscapular region; another individual exhibited
      neurological pruritus and scratching in the upper back but lacked CLA skin
      lesions. Both subjects presented with CLA or pruritic symptoms several years
      before the onset of medullary thyroid carcinoma (MTC) and/or pheochromocytoma.
      The remaining 15 RET mutation carriers did not exhibit CLA; of these, one
      presented with MTC and pheochromocytoma, nine with MTC only, two with elevated
      serum calcitonin and three younger subjects with normal serum calcitonin levels.
      This family's clinical data revealed a later diagnosis of MTC (mean age, 45.9
      (range: 23-73) years), a lower penetrance of pheochromocytoma (2/17, 11.8%) and
      CLA (1/17, 5.9%). However, no hyperparathyroidism and Hirschsprung disease were
      reported in this family. Summary and Conclusions: This is the first description
      of a family with MEN 2A-related CLA due to a germline RET C611Y mutation, which
      might exhibit a novel and diversified genotype-phenotype spectrum in MEN 2A.

PMID- 30300540
TI  - Vitamin D measurement and effect on outcome in a cohort of patients with heart
      failure
AB  - Objectives: The aims of this paper were to evaluate the levels of Vitamin D
      (VitD) in patients with heart failure (HF), compared to a control group, to
      assess the effects of VitD on HF outcome and to compare VitD measurement between
      LIAISON immunoassay and HPLC-MS-MS methods in this population. Design and
      Methods: We collected clinical, biochemical and outcome data from 247 patients
      with HF and in a subgroup of 151 patients, we measured VitD both with LIAISON and
      HPLC-MS-MS. Results: HF patients had statistically lower 25OHD levels (45.2 +/-
      23.7 nmol/L vs 58.2 +/- 24.0 nmol/L, P < 0.001) and a statistically higher
      prevalence of VitD insufficiency (61.1% vs 39.5%, P < 0.001) and deficiency
      (24.7% vs 6.6%, P < 0.001), compared to healthy controls. There was a significant
      inverse relationship between baseline 25OHD and risk of HF-related death, with a
      HR of 0.59 (95% CI 0.37-0.92, P = 0.02), confirmed in a multivariate adjusted
      analysis. Kaplan-Meier survival analyses showed that VitD insufficiency was
      associated with reduced survival in HF patients (log rank P = 0.017). There was a
      good agreement between LIAISON and HPLC-MS-MS (Cohen's kappa coefficient 0.70),
      but the prevalence of VitD insufficiency was significantly higher with the former
      compared to the latter method (58.3%, n = 88 vs 55.6%, n = 84, P < 0.001).
      LIAISON underestimated the 25OHD levels and showed a mean relative bias of 
      0.739% with 95% of limits of agreement (-9.00 to +7.52%), when compared to HPLC
      MS-MS. Conclusions: 25OHD levels adequately measured by HPLC-MS-MS showed to be
      low in HF population and to be correlated with HF-related risk of death.

PMID- 30300541
TI  - Serum anti-Mullerian hormone predicts ovarian response in (Macaca fascicularis)
      monkeys
AB  - AMH as a promising predictor of ovarian response has been studied extensively in
      women undergoing assisted reproductive technology treatment, but little is known
      about its prediction value in monkeys undergoing ovarian stimulation. In the
      current study, a total of 380 cynomolgus monkeys ranging from 5 to 12 years
      received 699 ovarian stimulation cycles. Serum samples were collected for AMH
      measure with enzyme-linked immunosorbent assay. It was found that serum AMH
      levels were positive correlated with the number of retrieved oocytes (P < 0.01)
      in the first, second and third stimulation cycles. In the first cycles, area
      under the curve (ROCAUC) of AMH is 0.688 for low response and 0.612 for high
      response respectively, indicating the significant prediction values (P = 0.000
      and P = 0.005). The optimal AMH cutoff value was 9.68 ng/mL for low ovarian
      response and 15.88 ng/mL for high ovarian response prediction. In the second
      stimulation cycles, the significance of ROCAUC of AMH for high response rather
      than the low response was observed (P = 0.001 and P = 0.468). The optimal AMH
      cutoff value for high ovarian response was 15.61 ng/mL. In the third stimulation
      cycles, AMH lost the prediction value with no significant ROCAUC. Our data
      demonstrated that AMH, not age, is a cycle-dependent predictor for ovarian
      response in form of oocyte yields, which would promote the application of AMH in
      assisted reproductive treatment (ART) of female cynomolgus monkeys. AMH
      evaluation would optimize candidate selection for ART and individualize the
      ovarian stimulation strategies, and consequentially improve the efficiency in
      monkeys.

PMID- 30300542
TI  - Hydrogen-Bond Assembly of Poly(vinyl alcohol) and Polyhexamethylene Guanidine for
      Nonleaching and Transparent Antimicrobial Films.
AB  - The combination of transparency, antimicrobial activities, nonleaching of
      antimicrobial component and green preparation for poly(vinyl alcohol) (PVA) films
      is of importance for practical applications in industry. However, until now it
      remains a challenge. Herein, a facile antimicrobial PVA films containing
      polyhexamethylene guanidine (PHMG) is reported via a green solution casting
      method. Such PVA films show high transparency of 91%, above 99.99% of
      antimicrobial rates against Escherichia coli and Staphylococcus aureus, and
      nonleaching characteristic of PHMG due to the hydrogen-bond (H-bond) interaction
      between PHMG and PVA. The thermal stability and mechanical properties of the PVA
      films are further improved compared to neat PVA film. These antimicrobial films
      are expected to find promising applications in tissue engineering and packaging
      fields, which opens up a methodology to prepare nonleaching antimicrobial
      polymeric materials via H-bond.

PMID- 30300543
TI  - Accelerating QM/MM Free Energy Computations via Intramolecular Force Matching.
AB  - The calculation of free energy differences between levels of theory has numerous
      potential pitfalls. Chief among them is the lack of overlap, i.e., ensembles
      generated at one level of theory (e.g., "low") not being good approximations of
      ensembles at the other (e.g., "high"). Numerous strategies have been devised to
      mitigate this issue. However, the most straightforward approach is to ensure that
      the "low" level ensemble more closely resembles that of the "high". Ideally, this
      is done without increasing computational cost. Herein, we demonstrate that by
      reparametrizing classical intramolecular potentials to reproduce high level
      forces (i.e., force matching) configurational overlap between a "low" (i.e.,
      classical) and "high" (i.e., quantum) level can be significantly improved. This
      procedure is validated on two test cases and results in vastly improved
      convergence of free energy simulations.

PMID- 30300544
TI  - Synthesis of Chiral Carbo-Nanotweezers for Enantiospecific Recognition and DNA
      Duplex Winding in Cancer Cells.
AB  - Targeting the DNA of tumor cells with small molecules may offer effective
      clinical strategies for transcriptional inhibition. We unveil synthesis and
      characterization of ~20 nm chiral carbon nanoparticles for enantiospecific
      recognition of DNA. Our approach inculcates chirality in carbon nanoparticles by
      controlled tethering of minor groove binders, i.e., Troger's base (TB). The
      chiral particles positively enriched the cellular nucleus in MCF-7 breast cancer
      cells, irrespective of the TB asymmetry tethered on the particle surface, but
      negatively induced chiral carbon nanoparticles exhibited improved efficiency at
      inhibiting cell growth. Further studies indicated that these chiral particles act
      as nanotweezers to perturb the genomic DNA and induce apoptosis cascade in cancer
      cells.

PMID- 30300545
TI  - Lipid-Polymer Bilaminar Oxygen Nanobubbles for Enhanced Photodynamic Therapy of
      Cancer.
AB  - Hypoxia in solid tumors may be a hindrance to effective treatments of tumors in
      achieving their therapeutic potential, especially for photodynamic therapy (PDT)
      which requires oxygen as the supplement substrate. Oxygen delivery using
      perfluorocarbon emulsions or lipid oxygen microbubbles has been developed as the
      agents to supply endogenous oxygen to fuel singlet oxygen generation in PDT.
      However, such methods suffer from premature oxygen release and storage issues. To
      address these limitations, we designed lipid-polymer bilaminar oxygen nanobubbles
      with chlorin e6 (Ce6) conjugated to the polymer shell as a novel oxygen self
      supplement agent for PDT. The resultant nanobubbles possessed excellent stability
      to reduce the risk of premature oxygen release and were stored as freeze-dried
      powders to avoid shelf storage issues. In vitro and in vivo experimental results
      demonstrated that the nanobubbles exhibited much higher cellular uptake rates and
      tumor targeting efficiency compared to free Ce6. Using the oxygen nanobubbles for
      PDT, a significant enhancement of therapeutic efficacy and survival rates was
      achieved on a C6 glioma-bearing mice model with no noticeable side effects, owing
      to the greatly enhanced singlet oxygen generation powered by oxygen encapsulated
      nanobubbles.

PMID- 30300546
TI  - Metabolic Engineering of Escherichia coli for High Yield Production of Succinic
      Acid Driven by Methanol.
AB  - Methanol is increasingly becoming an attractive carbon feedstock for the
      production of various biochemicals due to its high abundance and low price. In
      this study, when methanol assimilation module was introduced into succinic acid
      producing Escherichia coli by employing the NAD-dependent methanol dehydrogenase
      from Bacillus methanolicus and ribulose monophosphate pathway from different
      donor organisms, succinic acid yield was increased from 0.91 +/- 0.08 g/g to 0.98
      +/- 0.11 g/g with methanol as an auxiliary substrate under the anaerobic
      fermentation. Further 13C-labeling experiments showed that the recombinant strain
      successfully converted methanol into succinic acid, as the carbon atom of
      carboxyl group in succinic acid was labeled by 13C. It was found that the NADH
      generated by methanol oxidation would benefit succinate production, as the
      NADH/NAD+ ratio in vivo was decreased from 0.67 to 0.45 in the engineered strain,
      indicating that the efficiency of succinic acid synthesis was significantly
      improved when driven by methanol. This study represents a successful case for the
      development of reducing chemical production using methanol as an auxiliary
      substrate.

PMID- 30300547
TI  - Successive Surface Reactions on Hydrophilic Silica for Modified Magnetic
      Nanoparticle Attachment Probed by Sum-Frequency Generation Spectroscopy.
AB  - Successive surface reactions on hydrophilic silica substrates were designed and
      performed to immobilize ethanolamine-modified magnetic ferrite-based nanoparticle
      (NP) for surface characterization. The various surfaces were monitored using sum
      frequency generation (SFG) spectroscopy. The surface of the hydrophilic quartz
      substrate was first converted to a vinyl-terminated surface by utilizing a
      silanization reaction, and then, the surface functional groups were converted to
      carboxylic-terminated groups via a thiol-ene reaction. The appearance and
      disappearance of the vinyl (?CH2) peak at ~2990 cm-1 in the SFG spectra were
      examined to confirm the success of the silanization and thiol-ene reactions,
      respectively. Acyl chloride (-COCl) formation from carboxy (-COOH) functional
      group was then performed for further attachment of magnetic amine-functionalized
      magnesium ferrite nanoparticles (NPs) via amide bond formation. The scattered NPs
      attached on the modified silica substrate was then used to study the changes in
      the spectral profile of the ethanolamine modifier of the NPs for in situ lead(II)
      (Pb2+) adsorption at the solid-liquid interface using SFG spectroscopy. However,
      due to the limited number of NPs attached and sensitivity of SFG spectroscopy
      toward expected change in the modifier spectroscopically, no significant change
      was observed in the SFG spectrum of the modified silica with magnetic NPs during
      exposure to Pb2+ solution. Nevertheless, SFG spectroscopy as a surface technique
      successfully monitored the modifications from a clean fused substrate to -COCl
      formation that was used to immobilize the decorated magnetic nanoparticles. The
      method developed in this study can provide a reference for many surface or
      interfacial studies important for selective attachment of adsorbed organic or
      inorganic materials or particles.

PMID- 30300548
TI  - pH and Temperature Dual-Responsive Plasmonic Switches of Gold Nanoparticle
      Monolayer Film for Multiple Anticounterfeiting.
AB  - Two-dimensional (2D) gold nanoparticle (Au NP) monolayer film possesses a lot of
      fascinating peculiarities, and has shown promising applications in
      photoelectrical devices, catalysis, spectroscopy, sensors, and
      anticounterfeiting. Because of the localized surface plasmon resonance (LSPR)
      property predetermined by the natural structure of metal nanoparticles, it is
      usually difficult to realize the reversible LSPR transition of 2D film. In this
      work, we report on the fabrication of a large-area free-standing Au NP monolayer
      film with dual-responsive switchable plasmonic property using a pH- or thermal
      responsive dendronized copolymer as a stimuli-sensitive linker. In this system,
      an oligoethylene-glycol-based (OEG-based) dendronized copolymer (named PG1A) with
      pH or temperature sensitivity was first modified onto the surface of a Au NP.
      Then, polyethylene glycol dibenzyl aldehyde (PEG-DA) was introduced to interact
      with the amino moieties from PG1A before the process of oil-water interfacial
      self-assembly of NPs, resulting in an elastic, robust, pH- or temperature
      sensitive interpenetrating network among Au NPs in monolayer films. In addition,
      the film could exhibit reversibly plasmonic shifts of about 77 nm and inherent
      color changes through varying temperature or pH. The obtained free-standing
      monolayer film also shows an excellent transferable property, which can be easily
      transferred onto substrates such as plastic molds, PDMS, copper grids, and
      silicon wafers. In virtue of these peculiarities of the free-standing property,
      special plasmonic signal, and homologous macroscopic color, the transferred film
      was primely applied to an anticounterfeiting security label with clear color
      change at the designed spots, providing a new avenue to plasmonic nanodevices
      with various applications.

PMID- 30300549
TI  - Individual Variability of Protein Expression in Human Tissues.
AB  - Human tissues are known to exhibit interindividual variability, but a deeper
      understanding of the different factors affecting protein expression is necessary
      to further apply this knowledge. Our goal was to explore the proteomic
      variability between individuals as well as between healthy and diseased samples,
      and to test the efficacy of machine learning classifiers. In order to investigate
      whether disparate proteomics data sets may be combined, we performed a
      retrospective analysis of proteomics data from 9 different human tissues. These
      data sets represent several different sample prep methods, mass spectrometry
      instruments, and tissue health. Using these data, we examined interindividual and
      intertissue variability in peptide expression, and analyzed the methods required
      to build accurate tissue classifiers. We also evaluated the limits of tissue
      classification by downsampling the peptide data to simulate situations where less
      data is available, such as clinical biopsies, laser capture microdissection or
      potentially single-cell proteomics. Our findings reveal the strong potential for
      utilizing proteomics data to build robust tissue classifiers, which has many
      prospective clinical applications for evaluating the applicability of model
      clinical systems.

PMID- 30300550
TI  - A New Strategy for Intestinal Drug Delivery via pH-Responsive and Membrane-Active
      Nanogels.
AB  - Oral administration of hydrophobic and poorly intestinal epithelium-permeable
      drugs is a significant challenge. Herein, we report a new strategy to overcome
      this problem by using novel, pH-responsive, and membrane-active nanogels as drug
      carriers. Prepared by simple physical cross-linking of amphiphilic pseudopeptidic
      polymers with pH-controlled membrane-activity, the size and hydrophobicity
      hydrophilicity balance of the nanogels could be well-tuned. Furthermore, the
      amphiphilic nanogels could release hydrophobic payloads and destabilize cell
      membranes at duodenum and jejunum pH 5.0-6.0, which suggests their great
      potential for intestinal drug delivery.

PMID- 30300551
TI  - Encapsulation and Release of Essential Oils in Functional Silica Nanocontainers.
AB  - We describe the fabrication of mesoporous silica nanocontainers (SiO2NCs) that
      simultaneously encapsulate different antiseptic agents. Peppermint oil (PO),
      thyme oil (TO), cinnamon oil (CnO), and clove oil (CO), which are known to
      display antibacterial properties, are loaded in the core of the silica
      nanocontainers that are stabilized by antiseptic surfactants. The encapsulation
      efficiency, surface area, and pore size are controlled by the type of oil and
      surfactant. The release of essential oils is further controlled by grafting
      oxidized hyaluronic acid on silica nanocontainers functionalized with amino
      groups.

PMID- 30300552
TI  - Phase-Transferable Force Field for Alkali Halides.
AB  - A longstanding goal of computational chemistry is to predict the state of
      materials in all phases with a single model. This is particularly relevant for
      materials that are difficult or dangerous to handle or compounds that have not
      yet been created. Progress toward this goal has been limited, as most work has
      concentrated on just one phase, often determined by particular applications. In
      the framework of the development of the Alexandria force field, we present here
      new polarizable force fields for alkali halides with Gaussian charge
      distributions for molecular dynamics simulations. We explore different
      descriptions of the van der Waals interaction, like the commonly applied 12-6
      Lennard-Jones (LJ), and compare it to "softer" ones, such as the 8-6 LJ,
      Buckingham, and a modified Buckingham potential. Our results for physicochemical
      properties of the gas, liquid, and solid phases of alkali halides are compared to
      experimental data and calculations with reference polarizable and nonpolarizable
      force fields. The new polarizable force field that employs a modified Buckingham
      potential predicts the tested properties for gas, liquid, and solid phases with a
      very good accuracy. In contrast to reference force fields, this model reproduces
      the correct crystal structures for all alkali halides at low and high
      temperature. Seeing that experiments with molten salts may be tedious due to high
      temperatures and their corrosive nature, the models presented here can contribute
      significantly to our understanding of alkali halides in general and melts in
      particular.

PMID- 30300553
TI  - Early Emergency General Surgery Is Associated with a Higher Incidence of
      Clostridium difficile Infection.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is an important surgical
      complication. Emergency general surgery (EGS) is a developing area of the acute
      care surgical practice. Few studies evaluating the incidence and risk factors of
      CDI in this patient population are available. PATIENTS AND METHODS: A
      prospectively maintained Acute and Critical Care Surgery registry spanning from
      2008 to 2015 was queried for cases of operative EGS with clinical suspicion of
      CDI post-operatively. Diagnosis of CDI was made using toxin A/B assay in stools.
      Demographics, co-morbidities, surgical procedures, length of stay (LOS),
      intensive care unit LOS, antibiotic use, and death were obtained. The patients
      positive and negative for CDI were compared using chi-squared and Student's t
      test. Multi-variable logistic regression was used to determine risk factors for
      CDI. RESULTS: A total of 550 patients were identified. The total incidence of CDI
      was 12.7%. There was no significant difference in demographics between CDI
      positive and negative patients. Average time to CDI diagnosis was 10.1 +/- 8.5
      days post-operatively. Patients who received three or more antibiotic classes
      were at higher risk of CDI developing post-operatively (83% vs. 75%, p = 0.04).
      The CDI positive patients underwent an EGS significantly earlier than CDI
      negative patients (0.9 +/- 2.3 vs. 3.2 +/- 9.2 days, p < 0.001). The most common
      procedures were partial colectomies (21.4%); small bowel resections/repairs
      (12.9%); gastric repair for perforated peptic ulcer (10%); skin and soft tissue
      procedure (7.1%), and laparotomies (5.7%). There was no difference in outcomes
      between the groups. On linear regression, an EGS performed later after admission
      was an independent risk factor for lower CDI (OR 0.87; CI 95% [0.79-0.96], p <
      0.01). CONCLUSION: Patients undergoing an early EGS have a high incidence of CDI.
      The number of antibiotic classes administered post-operatively affects CDI
      status. Bowel resections appear to be at increased risk for CDI. Clinicians
      should have a high index of suspicion and low threshold for testing C. difficile
      in high-risk EGS patients.

PMID- 30300555
TI  - Linking Opioid-Overdose Data to Human Services and Criminal Justice Data:
      Opportunities for Intervention.
AB  - OBJECTIVES:: In Allegheny County, Pennsylvania, the incidence of opioid-related
      overdose deaths increased from 17.4 per 100 000 population in 2008 to 23.9 per
      100 000 population in 2014. Our objectives were to describe local demographic
      characteristics of this epidemic, identify public human services targets for
      intervention, determine temporal relationships between use of public human
      services and overdose mortality, and provide recommendations about potentially
      beneficial interventions. METHODS:: We used autopsy data from the Allegheny
      County Medical Examiner to link people who died of overdoses from 2008 through
      2014 to their premortem incarcerations and use of mental health services and
      substance use disorder services. We calculated the frequency of use of public
      human services by decedents and the interval between the last use of these
      services and overdose death. RESULTS:: Of the 1399 decedents, 957 (68.4%) had a
      public human service encounter before overdose death. Of these 957 decedents, 531
      (55.5%) had ever been incarcerated, 616 (64.4%) had ever used a mental health
      service, and 702 (73.4%) had ever used a substance use disorder service. Of 211
      decedents incarcerated in the year before their overdose death, 54 (25.6%)
      overdosed within 30 days of their last release from jail. Of 510 decedents using
      mental health services in the year before death, 231 (45.3%) overdosed within 30
      days of their last use of the services. Of 350 decedents using substance use
      disorder services in the year before their overdose death, 134 (38.3%) overdosed
      within 30 days of their last use of the services. CONCLUSIONS:: Merging data on
      overdose mortality with data on use of public human services can be a useful
      strategy to identify trends in, and factors contributing to, the opioid epidemic;
      to target interventions; and to stimulate collaboration to address the epidemic.

PMID- 30300556
TI  - Taking Opportunity Costs Seriously in Public Health Law.

PMID- 30300557
TI  - In Vitro Flow Rate Dependency of Delivered Dose and Fine Particle Dose of
      Salmeterol/Fluticasone Propionate Easyhaler and Seretide Diskus with Patient Flow
      Rates Collected in a Randomized Controlled Trial.
AB  - BACKGROUND: The Easyhaler(r) device-metered dry powder inhaler containing
      Salmeterol and Fluticasone propionate (S/F) has been developed for the treatment
      of patients with asthma and chronic obstructive pulmonary disease (COPD). We
      report two studies which evaluated the in vitro flow rate dependence of delivered
      dose (DD) and fine particle dose (FPD) of S/F Easyhaler versus Seretide
      Diskus(r). METHODS: A randomized controlled trial (RCT) assessed inspiratory flow
      parameters of S/F Easyhaler and Seretide Diskus in subgroups of patients with
      asthma (children, adolescents and adults, and elderly) and in COPD patients. The
      10th, 50th, and 90th percentile airflow rates were determined and utilized in
      vitro, to evaluate flow rate dependence of DD and FPD. Flow rate dependence was
      evaluated relative to the result obtained at the 50th percentile and any values
      deviating from 100% indicated flow rate dependence. The volumetric flow rate
      dependence (Q) index derived from FPD at 10th and 90th percentile airflows was
      also evaluated. RESULTS: Overall, 227 patients were enrolled and randomized; 216
      completed the RCT. In total, 55.5% of patients were female, and the mean age was
      46.3 years. Clinically relevant airflow rates (46, 68, and 85 L/min for S/F
      Easyhaler and 44, 71, and 96 L/min for Seretide Diskus) were carried forward into
      the in vitro study, which demonstrated similar flow rate dependence of DD and FPD
      for S/F Easyhaler compared with Seretide Diskus; all values were within +/-15%
      limits across the 10th, 50th, and 90th percentile airflow rates. Q index results
      suggested that both S/F Easyhaler and Seretide Diskus are medium airflow
      dependent products. CONCLUSIONS: Similar in vitro flow rate dependence of DD and
      FPD was demonstrated for S/F Easyhaler compared with Seretide Diskus, across a
      range of clinically relevant airflow rates, collected from patients with asthma
      and COPD.

PMID- 30300558
TI  - The Problematic Role of Public Health in Washington, DC's, Urban Renewal.

PMID- 30300559
TI  - Concentric Group Therapy for Aggression: A Historical Perspective.
AB  - The purpose of this study is to present themes from a novel group therapy
      intervention for veterans with aggression. The groups were designed based on a
      psychodynamic rather than cognitive?behavioral theoretical framework, in which
      there are two overlapping short and long-term groups. Content analysis revealed
      six themes including, control your anger, helplessness, improvement,
      disagreements, where are the boundaries, and co-leadership, parallel process.
      This unique and innovative approach for the treatment of veterans with a history
      of aggressive behavior helped improved their understanding of aggression and
      decreased these behaviors. This group model may also have potential to be
      expanded to other patient populations with similar behaviors.

PMID- 30300561
TI  - Fecal Microbiota Transplantation for the Management of Clostridium difficile
      Infection.
AB  - The clinical burden of Clostridium difficile infection (CDI) continues to grow.
      Despite the multitude of treatment options that have been developed and tested to
      combat the morbidity and death associated with CDI, recurrence remains common. As
      such, treatment modalities such as fecal microbiota transplantation (FMT) have
      become studied increasingly; FMT serves to transplant stool from carefully
      selected healthy subjects into C. difficile positive patients through a variety
      of delivery routes. In doing so, FMT is hypothesized to correct dysbiosis of the
      recipient gut microbiome addressing the root cause of the pathogenesis of C.
      difficile infection. A growing body of evidence shows FMT to be efficacious in
      this setting, and the study of FMT accordingly continues to evolve to identify
      novel indications for its utilization.

PMID- 30300560
TI  - Racial/Ethnic Disparities in Influenza Vaccination Coverage Among US Adolescents,
      2010-2016.
AB  - OBJECTIVE:: Although research suggests racial/ethnic disparities in influenza
      vaccination and mortality rates, few studies have examined racial/ethnic trends
      among US adolescents. We used national cross-sectional data to determine (1)
      trends in influenza vaccination rates among non-Hispanic white (hereinafter,
      white), non-Hispanic black (hereinafter, black), and Hispanic adolescents over
      time and (2) whether influenza vaccination rates among adolescents varied by
      race/ethnicity. METHODS:: We analyzed provider-reported vaccination histories for
      2010-2016 from the National Immunization Survey-Teen. We used binary logistic
      regression models to determine trends in influenza vaccination rates by
      race/ethnicity for 117 273 adolescents, adjusted for sex, age, health insurance,
      physician visit in the previous 12 months, vaccination facility type, poverty
      status, maternal education level, children in the household, maternal marital
      status, maternal age, and census region of residence. We calculated adjusted
      probabilities for influenza vaccination for each racial/ethnic group, adjusted
      for the same demographic characteristics. RESULTS:: Compared with white
      adolescents, Hispanic adolescents had higher odds (adjusted odds ratio [aOR] =
      1.11; 95% confidence interval [CI], 1.06-1.16) and black adolescents had lower
      odds (aOR = 0.95; 95% CI, 0.90-1.00) of vaccination. Compared with white
      adolescents, Hispanic adolescents had significantly higher adjusted probabilities
      of vaccination for 2011-2013 (2011: 0.22, P < .001; 2012: 0.23, P < .001; 2013:
      0.26, P < .001). Compared with white adolescents, black adolescents had
      significantly lower probabilities of vaccination for 2016 (2016: 0.21, P < .001).
      CONCLUSIONS:: Targeted interventions are needed to improve adolescent influenza
      vaccination rates and reduce racial/ethnic disparities in adolescent vaccination
      coverage.

PMID- 30300563
TI  - Antiseptic Irrigation as an Effective Interventional Strategy for Reducing the
      Risk of Surgical Site Infections.
AB  - A surgical site infection (SSI) can occur at several anatomic sites related to a
      surgical procedure: Superficial or deep incisional or organ/space. The SSIs are
      the leading cause of health-care-associated infection (HAI) in industrialized
      Western nations. Patients in whom an SSI develops require longer hospitalization,
      incur significantly greater treatment costs and reduction in quality of life, and
      after selective surgical procedures experience higher mortality rates. Effective
      infection prevention and control requires the concept of the SSI care bundle,
      which is composed of a defined number of evidence-based interventional
      strategies, because of the many risk factors that can contribute to the
      development of an SSI. Intra-operative irrigation has been a mainstay of surgical
      practice for well over 100 years, but lacks standardization and compelling
      evidence-based data to validate its efficacy. In an era of antibiotic
      stewardship, with a widespread prevalence of bacterial resistance to multiple
      antibiotic agents, there has emerged an interest in using intra-operative
      antiseptic irrigation to reduce microbial contamination in the surgical site
      before closure and possibly reduce the need for antibiotic agents. This approach
      has gained added appeal in an era of biomedical device implantation, especially
      with the recognition that most, if not all, device-related infections are
      associated with biofilm formation. This review focuses on the limited, evidence
      based rationale for the use of antiseptic agents as an effective risk reduction
      strategy for prevention of SSIs.

PMID- 30300564
TI  - Bioinformatics Analysis and Competitive Regulation by Transcription Factors of
      SIRT5 at the Core Promoter Region Using Bovine Adipocytes.
AB  - Sirtuin 5 (SIRT5) belongs to the mitochondrial sirtuin family, which constitutes
      a highly conserved family of nicotinamide adenine dinucleotide NAD+-dependent
      deacetylases and ADP-ribosyltransferases that play an important regulatory role
      in stress resistance and metabolic homeostasis. SIRT5, a member of the
      mitochondrial sirtuins, has been confirmed to exhibit deacetylase, desuccinylase,
      and demalonylase enzymatic activities. First, we showed that SIRT5 was expressed
      at the highest level in the bovine testis, followed by longissimus thoracis and
      subcutaneous adipose tissue, using real-time quantitative PCR and mRNA levels of
      SIRT5 during adipocyte differentiation, which increased before the first day and
      then decreased rapidly. To explore the molecular regulation of bovine SIRT5
      expression, we cloned a 2-kb fragment of the 5'-regulatory region and the
      functional proximal minimal promoter of bovine SIRT5. Electrophoretic mobility
      shift assays and luciferase reporter assays identified Kruppel-like factor 2
      (KLF2), CCAAT enhancer binding protein beta (CEBPbeta), peroxisome proliferator
      activated receptor alpha (PPARalpha), myogenic differentiation 1 (MYOD), and
      nuclear respiratory factor 1 (NRF1) binding sites as transcriptional activators
      or repressors in the core promoter region of SIRT5. In brief, our study focused
      on the mechanism underlying the transcriptional regulation of SIRT5 expression in
      bovine adipocytes.

PMID- 30300565
TI  - Juxtafacial Lipoma within the Mastoid Bone.

PMID- 30300566
TI  - Can There Be Acceptable Prison Health Care? Looking Back on the 1970s.

PMID- 30300567
TI  - The Effect of Pectins on Water Crystallization Pattern and Integrity of Cells
      During Freezing.
AB  - The ability of various pectin polysaccharides to modify the morphological
      structure of ice during the phase transitions from water to ice was studied.
      Pectins were isolated from Sosnowsky's hogweed Heracleum sosnowskyi Manden
      (heracleuman-N6HS), tansy Tanacetum vulgare L. (tanacetan-N7TVF), and Rauwolfia
      serpentina Benth callus (rauwolfian-N8RS). Pectins were isolated by multistep
      extraction. The effect of pectins was assessed using osmometry, thermographic
      analysis, and cryomicroscopy. A concentrate of leukocytes was used as the sample
      for the subsequent freezing step. The condition of the leukocyte membrane, and
      lysosomal and phagocytic activity after a freezing-warming process were assessed.
      Osmotic concentrations of the pectin polysaccharide solutions were found to be
      very low. The 0.4 wt % N7TVF solution had the highest osmotic concentration as
      well as freezing point; however, the duration of its crystallization plateau was
      lower than that of the 0.4 wt % and 0.2 wt % N6HS solutions. All studied
      polysaccharide solutions demonstrated a high linear rate of ice crystal growth.
      There were statistically significant differences between the melting rates for
      the 0.2% solutions of the pectins, N6HS and N7TVF, N6HS and N8RS, as well as
      between concentrations for the pectin N7TVF and between concentrations for the
      pectin N8RS. The data on the integrity of cells that are frozen in a medium
      containing polysaccharides may indicate a cryoprotective effect of the N7TVF and
      N8RS pectins, that is, tanacetan from tansy and rauwolfian from rauwolfia. The
      most effective modifier among the substances, which were studied by us, was the
      N7TVF pectin polysaccharide (tanacetan from tansy).

PMID- 30300568
TI  - An Academic-Practice Partnership at the University of Washington School of Public
      Health: The Student Epidemic Action Leaders (SEAL) Team.
AB  - In 2015, the University of Washington School of Public Health, Department of
      Epidemiology established the Student Epidemic Action Leaders (SEAL) team to
      provide public health students with experience in field epidemiology in state and
      local public health communicable disease divisions. The University of Washington
      Department of Epidemiology developed the SEAL team in collaboration with the
      Washington State Department of Health to offer public health graduate students
      opportunities to contribute to the real-time needs of public health agencies
      during a communicable disease event and/or preparedness event. The SEAL team
      combines classroom and field-based training in public health practice and applied
      epidemiology. During the first 2 years of the SEAL team (2016-2018), 34 SEALs
      were placed at 4 agencies contributing more than 1300 hours of assistance on 24
      public health projects.

PMID- 30300569
TI  - Microbe Isolation from Blood, Central Venous Catheters, and Fluid Collections
      after Liver Resections.
AB  - BACKGROUND: Our goal was to evaluate the microbe species responsible for
      bacteremia or infections related to central venous catheter (CVC) or fluid
      collections after liver resection. PATIENTS AND METHODS: Data from 112 patients
      (68 males, 44 females) who underwent liver resection over a period of 63 months
      were reviewed. Patient and tumor characteristics, intra-operative and post
      operative data, and the results from cultures of peripheral blood, CVC tips and
      drained intra-abdominal or intra-throracic fluid collections were collected.
      RESULTS: There were positive blood cultures in 20 patients (17.9%). Coagulase
      negative staphylococci (CoNS) and bacteria of enteric flora were the micro
      organisms found most frequently and half of the cases had multiple isolated
      microbe species. The construction of a bilioenteric anastomosis was an
      independent risk factor for microbe isolation in peripheral blood (odds ratio
      [OR]: 11, p = 0.01). Furthermore, there were positive cultures of the CVC tip in
      14 patients (12.5%), with CoNS being the micro-organism found most frequently and
      most cases had only one isolated microbe species. No specific risk factor for
      catheter-related infections was detected. In addition, there were positive
      cultures of drained fluid collections in 19 patients (17%), with bacteria of
      enteric flora being the micro-organisms found most frequently and the majority of
      cases had multiple isolated microbe species. The construction of a bilioenteric
      anastomosis (OR: 23.5, p = 0.002) and the laparoscopic approach (OR: 4.7, p =
      0.0496) were independent risk factors for microbe isolation in drained fluid
      collections. Finally, the presence of positive blood cultures was associated with
      the presence of positive culture of CVC tips (p = 0.018) and drained fluid
      collections (p = 0.001). CONCLUSIONS: Post-operative bacteremia, colonization of
      CVCs, and contamination of fluid collections occur frequently after liver
      resections and various microbe species may be involved. Patients who undergo
      hepatectomy and a synchronous construction of a bilioenteric anastomosis are at
      increased risk of bacteremia development and contamination of fluid collections.

PMID- 30300570
TI  - Losing our soul: American values.

PMID- 30300571
TI  - Development of an Embryonic Zebrafish Oligodendrocyte-Neuron Mixed Coculture
      System.
AB  - During vertebrate neural development, oligodendrocytes insulate nerve axons with
      myelin sheaths. Zebrafish (Danio rerio) has emerged as a useful model organism
      for studying oligodendrocyte development. However, the absence of an in vitro
      culture system necessitates in vivo manipulations and analyses, which, in some
      instances, limits the questions that can be addressed. To fill this gap we
      developed a mixed coculture system for embryonic zebrafish neurons and
      oligodendrocyte-lineage cells. Cultures harvested from embryos >=30 hours
      postfertilization (hpf) yielded oligodendrocyte progenitor cells (OPCs) positive
      for olig2 and sox10 transgenic reporters. Cultured OPCs exhibited dynamic,
      exploratory membrane processes, and cell morphologies resembled those established
      in vivo. Cells harvested from advanced stage embryos possessed more arborized
      processes than those from early stage embryos. Advanced stage (>60 hpf) embryo
      culture produced differentiated, mbp+ oligodendrocytes. Genetically tractable
      neuron subtypes extended neurites when harvested from embryos >=19 hpf. Coculture
      produced juxtaposed oligodendrocytes and neurons, demonstrating the practical
      usefulness of this technique for future studies examining axon-oligodendrocyte
      interactions under defined conditions. We expect that zebrafish oligodendrocyte
      culture will complement existing in vivo strengths and may facilitate future
      studies elucidating the mechanisms of oligodendrocyte specification,
      proliferation, differentiation, motility, and axon-oligodendrocyte interactions
      that shape adult myelination patterns.

PMID- 30300572
TI  - Motor Neuron Abnormalities Correlate with Impaired Movement in Zebrafish that
      Express Mutant Superoxide Dismutase 1.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by progressive loss of motor neurons. ALS can be modeled in
      zebrafish (Danio rerio) through the expression of human ALS-causing genes, such
      as superoxide dismutase 1 (SOD1). Overexpression of mutated human SOD1 protein
      causes aberrant branching and shortening of spinal motor axons. Despite this, the
      functional relevance of this axon morphology remains elusive. Our aim was to
      determine whether this motor axonopathy is correlated with impaired movement in
      mutant (MT) SOD1-expressing zebrafish. Transgenic zebrafish embryos that express
      blue fluorescent protein (mTagBFP) in motor neurons were injected with either
      wild-type (WT) or MT (A4V) human SOD1 messenger ribonucleic acid (mRNA). At 48
      hours post-fertilization, larvae movement (distance traveled during behavioral
      testing) was examined, followed by quantification of motor axon length. Larvae
      injected with MT SOD1 mRNA had significantly shorter and more aberrantly branched
      motor axons (p < 0.002) and traveled a significantly shorter distance during
      behavioral testing (p < 0.001) when compared with WT SOD1 and noninjected larvae.
      Furthermore, there was a positive correlation between distance traveled and motor
      axon length (R2 = 0.357, p < 0.001). These data represent the first correlative
      investigation of motor axonopathies and impaired movement in SOD1-expressing
      zebrafish, confirming functional relevance and validating movement as a disease
      phenotype for the testing of disease treatments for ALS.

PMID- 30300573
TI  - Contribution of Vaccination to the Reduction of Infectious Mortality in Ukraine
      in the Second Half of the 20th and Early 21st Century: A Comparative Population
      Based Study of the Dynamics and Structure of Infectious Mortality and Incidence.
AB  - Our work presents an epidemiological analysis of the dynamics and structure of
      the annual indicators such as Cumulative Incidence, Mortality Rate (MR), and Case
      Fatality Rate for infections preventable by vaccines (vaccine-preventable
      infections-VPIs) in Ukraine between 1944 and 2015 compared to the same indicators
      for infections not preventable by vaccines (nonvaccine-preventable infections-non
      VPIs). In 1965, the proportion of all infectious diseases in the context of
      mortality (7.47%), and especially of VPI (3.77%), including those registered
      among children aged 0-14 years (2.12%), testifies to the low profile of
      infectious diseases by the time of routine vaccination introduction. The analyses
      of these particular data are important with respect to the role of vaccination
      programs in reducing not only the total infectious mortality but also mortality
      related to VPIs in the twentieth century. Interestingly, in Ukraine between 1965
      and 2015, similar rates of mortality reduction were observed in both the total
      population (1.6-2.6 times) and in children under 14 (15.2-20.4 times) for both
      VPIs and non-VPIs. During the 1944-2015 period in Ukraine, the reduction of MR of
      VPI (tuberculosis, diphtheria, tetanus, pertussis, poliomyelitis, measles, and
      hepatitis B) varied greatly, ranging from 40.5 times (tetanus) to 1,061.1 times
      (measles), but in general, the reduction incidence rate of VPI was significantly
      lower ranging from 42.4 times (measles) to 471.1 times (diphtheria). The ratio of
      incidence and mortality reduction in percent shows the contribution of
      vaccination to the mortality reduction for various infections during 1944-2015.
      This ratio ranged from 0% (tuberculosis) to 84.9% (tetanus), provided that the
      reduction of the VPI incidence 100% depends on vaccine effects. Thus, we can
      assume that the observed reduction in mortality for some VPIs was, in part,
      caused by factors not associated with vaccines.

PMID- 30300574
TI  - Identification of a Novel Zebrafish Mutant Line that Develops Testicular Germ
      Cell Tumors.
AB  - Testicular tumors are the most common solid malignant tumors in men 20-35 years
      of age. Although most of testicular tumors are curable, current treatments still
      fail in 15%-20% of patients. However, insufficient understanding of the molecular
      basis and lack of animal models limit development of more effective treatments.
      This study reports the identification of a novel zebrafish mutant line, ns1402,
      which develops testicular germ cell tumors (TGCTs). While both male and female
      ns1402 mutants were fertile at young age, male ns1402 mutants became infertile as
      early as 9 months of age. This infertility was associated with progressive loss
      of mature sperm. Failure of spermatogenesis was, at least in part, explained by
      progressive loss of mature Leydig cells, a source of testosterone that is
      essential for spermatogenesis. Interestingly, TGCTs in ns1402 mutants contained a
      large number of Sertoli cells and gene expression profiles of Sertoli cells were
      altered before loss of mature Leydig cells. This suggests that changes in Sertoli
      cell properties happened first, followed by loss of mature Leydig cells and
      failure of spermatogenesis. Taken together, this study emphasizes the importance
      of cell-cell interactions and cell signaling in the testis for spermatogenesis
      and tissue homeostasis.

PMID- 30300575
TI  - Genetic Ancestry May Influence the Evolutionary Trajectory of Cancers.
AB  - In this issue of Cancer Cell, Yuan et al. compared the somatic alterations
      harbored by tumors from European and African ancestry individuals. They
      determined that the latter group has a propensity for aberrations that are
      consistent with genomic instability, potentially lending insight to the genomic
      basis of cancer health disparities.

PMID- 30300576
TI  - Complement C5a-Mediated TAM-ing of Antitumor Immunity Drives Squamous
      Carcinogenesis.
AB  - In this issue of Cancer Cell, Medler et al. demonstrate that fibrinolytic enzyme
      mediated generation of complement C5a reprograms tumor-infiltrating C5aR1+
      macrophages into an immunosuppressive phenotype that dampens CD8+ T cell
      responses during squamous carcinogenesis. C5aR1 blockade combined with
      chemotherapy offers a promising immunomodulatory strategy for treating squamous
      cell carcinoma.

PMID- 30300577
TI  - Intratumoral Heterogeneity: Tools to Understand and Exploit Clone Wars in AML.
AB  - In this issue of Cancer Cell, de Boer et al. refine a set of acute myeloid
      leukemia (AML)-enriched plasma membrane markers that can be used to identify,
      prospectively isolate, and longitudinally track leukemic subclones within
      individual AML patients, correlating immunophenotypic profiles with specific
      mutational signatures, transcription, functional behavior, and therapeutic
      outcomes.

PMID- 30300578
TI  - Integrated Analysis of Genetic Ancestry and Genomic Alterations across Cancers.
AB  - Disparities in cancer care have been a long-standing challenge. We estimated the
      genetic ancestry of The Cancer Genome Atlas patients, and performed a pan-cancer
      analysis on the influence of genetic ancestry on genomic alterations. Compared
      with European Americans, African Americans (AA) with breast, head and neck, and
      endometrial cancers exhibit a higher level of chromosomal instability, while a
      lower level of chromosomal instability was observed in AAs with kidney cancers.
      The frequencies of TP53 mutations and amplification of CCNE1 were increased in
      AAs in the cancer types showing higher levels of chromosomal instability. We
      observed lower frequencies of genomic alterations affecting genes in the PI3K
      pathway in AA patients across cancers. Our result provides insight into genomic
      contribution to cancer disparities.

PMID- 30300580
TI  - MYC Interacts with the G9a Histone Methyltransferase to Drive Transcriptional
      Repression and Tumorigenesis.
AB  - MYC is an oncogenic driver that regulates transcriptional activation and
      repression. Surprisingly, mechanisms by which MYC promotes malignant
      transformation remain unclear. We demonstrate that MYC interacts with the G9a
      H3K9-methyltransferase complex to control transcriptional repression. Inhibiting
      G9a hinders MYC chromatin binding at MYC-repressed genes and de-represses gene
      expression. By identifying the MYC box II region as essential for MYC-G9a
      interaction, a long-standing missing link between MYC transformation and gene
      repression is unveiled. Across breast cancer cell lines, the anti-proliferative
      response to G9a pharmacological inhibition correlates with MYC sensitivity and
      gene signatures. Consistently, genetically depleting G9a in vivo suppresses MYC
      dependent tumor growth. These findings unveil G9a as an epigenetic regulator of
      MYC transcriptional repression and a therapeutic vulnerability in MYC-driven
      cancers.

PMID- 30300579
TI  - Complement C5a Fosters Squamous Carcinogenesis and Limits T Cell Response to
      Chemotherapy.
AB  - Complement is a critical component of humoral immunity implicated in cancer
      development; however, its biological contributions to tumorigenesis remain poorly
      understood. Using the K14-HPV16 transgenic mouse model of squamous
      carcinogenesis, we report that urokinase (uPA)+ macrophages regulate C3
      independent release of C5a during premalignant progression, which in turn
      regulates protumorigenic properties of C5aR1+ mast cells and macrophages,
      including suppression of CD8+ T cell cytotoxicity. Therapeutic inhibition of
      C5aR1 via the peptide antagonist PMX-53 improved efficacy of paclitaxel
      chemotherapy associated with increased presence and cytotoxic properties of
      CXCR3+ effector memory CD8+ T cells in carcinomas, dependent on both macrophage
      transcriptional programming and IFNgamma. Together, these data identify C5aR1
      dependent signaling as an important immunomodulatory program in neoplastic tissue
      tractable for combinatorial cancer immunotherapy.

PMID- 30300582
TI  - Pharmacological Induction of RAS-GTP Confers RAF Inhibitor Sensitivity in KRAS
      Mutant Tumors.
AB  - Targeting KRAS mutant tumors through inhibition of individual downstream pathways
      has had limited clinical success. Here we report that RAF inhibitors exhibit
      little efficacy in KRAS mutant tumors. In combination drug screens, MEK and PI3K
      inhibitors synergized with pan-RAF inhibitors through an RAS-GTP-dependent
      mechanism. Broad cell line profiling with RAF/MEK inhibitor combinations revealed
      synergistic efficacy in KRAS mutant and wild-type tumors, with KRASG13D mutants
      exhibiting greater synergy versus KRASG12 mutant tumors. Mechanistic studies
      demonstrate that MEK inhibition induced RAS-GTP levels, RAF dimerization and RAF
      kinase activity resulting in MEK phosphorylation in synergistic tumor lines
      regardless of KRAS status. Taken together, our studies uncover a strategy to
      rewire KRAS mutant tumors to confer sensitivity to RAF kinase inhibition.

PMID- 30300581
TI  - Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and
      CD1d Targeting.
AB  - Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical
      remissions in CD19+ B cell lymphomas are often short lived. We tested whether
      CAR19-engineering of the CD1d-restricted invariant natural killer T (iNKT) cells
      would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively
      activated by CD1d- and CAR19-CD19-dependent interactions are more effective than
      CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter
      in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to
      eradicate brain lymphomas underpinned an improved tumor-free and overall
      survival. CD1D transcriptional de-repression by all-trans retinoic acid results
      in further enhanced cytotoxicity of CAR19-iNKT cells against CD19+ chronic
      lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for
      CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers.

PMID- 30300584
TI  - Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies.

PMID- 30300585
TI  - Non-conventional Inhibitory CD4+Foxp3-PD-1hi T Cells as a Biomarker of Immune
      Checkpoint Blockade Activity.

PMID- 30300583
TI  - The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to
      Drive Leukemic Transformation.
AB  - Oncogenic transcription factors such as the leukemic fusion protein RUNX1/ETO,
      which drives t(8;21) acute myeloid leukemia (AML), constitute cancer-specific but
      highly challenging therapeutic targets. We used epigenomic profiling data for an
      RNAi screen to interrogate the transcriptional network maintaining t(8;21) AML.
      This strategy identified Cyclin D2 (CCND2) as a crucial transmitter of RUNX1/ETO
      driven leukemic propagation. RUNX1/ETO cooperates with AP-1 to drive CCND2
      expression. Knockdown or pharmacological inhibition of CCND2 by an approved drug
      significantly impairs leukemic expansion of patient-derived AML cells and
      engraftment in immunodeficient murine hosts. Our data demonstrate that RUNX1/ETO
      maintains leukemia by promoting cell cycle progression and identifies G1 CCND-CDK
      complexes as promising therapeutic targets for treatment of RUNX1/ETO-driven AML.

PMID- 30300586
TI  - For Intestinal Homeostasis, You Are What You Eat.
AB  - Nutrients play a central role in controlling the form and function of the
      intestinal epithelium. In this issue of Developmental Cell, Mattila et al. (2018)
      and Obniski et al. (2018) uncover important mechanisms by which Drosophila
      intestinal stem cells respond to dietary signals, linking nutrients to tissue
      homeostasis.

PMID- 30300587
TI  - Single Cell and Open Chromatin Analysis Reveals Molecular Origin of Epidermal
      Cells of the Skin.

PMID- 30300588
TI  - Mechanical Force-Driven Adherens Junction Remodeling and Epithelial Dynamics.
AB  - During epithelial tissue development, repair, and homeostasis, adherens junctions
      (AJs) ensure intercellular adhesion and tissue integrity while allowing for cell
      and tissue dynamics. Mechanical forces play critical roles in AJs' composition
      and dynamics. Recent findings highlight that beyond a well-established role in
      reinforcing cell-cell adhesion, AJ mechanosensitivity promotes junctional
      remodeling and polarization, thereby regulating critical processes such as cell
      intercalation, division, and collective migration. Here, we provide an integrated
      view of mechanosensing mechanisms that regulate cell-cell contact composition,
      geometry, and integrity under tension and highlight pivotal roles for
      mechanosensitive AJ remodeling in preserving epithelial integrity and sustaining
      tissue dynamics.

PMID- 30300590
TI  - Neuroethology of bat navigation.

PMID- 30300591
TI  - Cryo-EM.
AB  - Eva Nogales introduces cryo-electron microscopy used to visualize macromolecular
      structures.

PMID- 30300592
TI  - Sleep spindles.
AB  - Schonauer and Pohlchen introduce the reader to sleep spindles, brain oscillations
      that occur during nREM sleep that are thought to function in the stabilization of
      memories.

PMID- 30300589
TI  - Combining Developmental and Perturbation-Seq Uncovers Transcriptional Modules
      Orchestrating Neuronal Remodeling.
AB  - Developmental neuronal remodeling is an evolutionarily conserved mechanism
      required for precise wiring of nervous systems. Despite its fundamental role in
      neurodevelopment and proposed contribution to various neuropsychiatric disorders,
      the underlying mechanisms are largely unknown. Here, we uncover the fine temporal
      transcriptional landscape of Drosophila mushroom body gamma neurons undergoing
      stereotypical remodeling. Our data reveal rapid and dramatic changes in the
      transcriptional landscape during development. Focusing on DNA binding proteins,
      we identify eleven that are required for remodeling. Furthermore, we sequence
      developing gamma neurons perturbed for three key transcription factors required
      for pruning. We describe a hierarchical network featuring positive and negative
      feedback loops. Superimposing the perturbation-seq on the developmental
      expression atlas highlights a framework of transcriptional modules that together
      drive remodeling. Overall, this study provides a broad and detailed molecular
      insight into the complex regulatory dynamics of developmental remodeling and thus
      offers a pipeline to dissect developmental processes via RNA profiling.

PMID- 30300593
TI  - Chromokinesins.
AB  - During the cell cycle it is critical that the duplicated DNA faithfully
      segregates to give rise to two genetically identical daughter cells. An even
      distribution of the genome during mitosis is mediated by mitotic spindle
      microtubules, assisted by, among others, motor proteins of the kinesin
      superfamily. Chromokinesins are members of the kinesin superfamily that harbour a
      specific DNA-binding domain. The best characterized chromokinesins belong to the
      kinesin-4/Kif4 and kinesin-10/Kif22 families, respectively. Functional analysis
      of chromokinesins in several model systems revealed their involvement in
      chromosome arm orientation and oscillations. This is consistent with their
      originally proposed role in the generation of polar ejection forces that assist
      chromosome congression to the spindle equator. Kinesin-12/Kif15 members comprise
      a third family of chromokinesins, but their role remains less understood.
      Noteworthy, all chromokinesins exhibit chromosome-independent localization on
      spindle microtubules, and recent works have significantly extended the portfolio
      of mitotic processes in which chromokinesins play a role, from error correction
      and DNA compaction, to the regulation of spindle microtubule dynamics.

PMID- 30300594
TI  - Avoiding death by feigning death.
AB  - Thanatosis is a common phenomenon in which prey appear to feign death when
      attacked by predators. It was once widely believed that thanatosis exploited
      predators' tendencies to avoid dead prey. However, this hypothesis has never been
      tested, and its feasibility has been questioned to the point that it has been
      largely abandoned [1,2]. Here, I show that naive birds quickly learned that dead
      Indian stick insects Carausius morosus were unpalatable, and subsequently
      rejected live insects that displayed thanatosis, but not those that failed to
      show thanatosis. Thanatosis had no effect on the behavior of birds that had never
      experienced dead insects, or those that had experienced dead insects whose
      resemblance to thanatosic insects had been destroyed. Therefore, thanatosis
      clearly caused predators to avoid prey that they mistakenly perceived to be dead.

PMID- 30300595
TI  - Marine plastics threaten giant Atlantic Marine Protected Areas.
AB  - There has been a recent shift in global perception of plastics in the
      environment, resulting in a call for greater action. Science and the popular
      media have highlighted plastic as an increasing stressor [1,2]. Efforts have been
      made to confer protected status to some remote locations, forming some of the
      world's largest Marine Protected Areas, including several UK overseas
      territories. We assessed plastic at these remote Atlantic Marine Protected Areas,
      surveying the shore, sea surface, water column and seabed, and found drastic
      changes from 2013-2018. Working from the RRS James Clark Ross at Ascension, St.
      Helena, Tristan da Cunha, Gough and the Falkland Islands (Figure 1A), we showed
      that marine debris on beaches has increased more than 10 fold in the past decade.
      Sea surface plastics have also increased, with in-water plastics occurring at
      densities of 0.1 items m-3; plastics on seabeds were observed at <= 0.01 items m
      2. For the first time, beach densities of plastics at remote South Atlantic sites
      approached those at industrialised North Atlantic sites. This increase even
      occurs hundreds of meters down on seamounts. We also investigated plastic
      incidence in 2,243 animals (comprising 26 species) across remote South Atlantic
      oceanic food webs, ranging from plankton to seabirds. We found that plastics had
      been ingested by primary consumers (zooplankton) to top predators (seabirds) at
      high rates. These findings suggest that MPA status will not mitigate the threat
      of plastic proliferation to this rich, unique and threatened biodiversity.

PMID- 30300596
TI  - Protection against the lethal side effects of social immunity in ants.
AB  - Many animals use antimicrobials to prevent or cure disease [1,2]. For example,
      some animals will ingest plants with medicinal properties, both prophylactically
      to prevent infection and therapeutically to self-medicate when sick.
      Antimicrobial substances are also used as topical disinfectants, to prevent
      infection, protect offspring and to sanitise their surroundings [1,2]. Social
      insects (ants, bees, wasps and termites) build nests in environments with a high
      abundance and diversity of pathogenic microorganisms - such as soil and rotting
      wood - and colonies are often densely crowded, creating conditions that favour
      disease outbreaks. Consequently, social insects have evolved collective disease
      defences to protect their colonies from epidemics. These traits can be seen as
      functionally analogous to the immune system of individual organisms [3,4]. This
      'social immunity' utilises antimicrobials to prevent and eradicate infections,
      and to keep the brood and nest clean. However, these antimicrobial compounds can
      be harmful to the insects themselves, and it is unknown how colonies prevent
      collateral damage when using them. Here, we demonstrate that antimicrobial acids,
      produced by workers to disinfect the colony, are harmful to the delicate pupal
      brood stage, but that the pupae are protected from the acids by the presence of a
      silk cocoon.

PMID- 30300597
TI  - Roads threaten Asiatic cheetahs in Iran.
AB  - Wildlife-vehicle collisions are an important cause of mortality for many animal
      species. They also prove extremely detrimental to the critically endangered
      Asiatic cheetah (Acinonyx jubatus venaticus) [1,2]. One to two Asiatic cheetahs
      are killed by vehicles on Iran's roads annually [3,4]. As such, the Asiatic
      cheetah could be the next charismatic felid subspecies to go extinct in the near
      future [5]. We identified one statistically-significant cluster of cheetah
      vehicle collisions on the Shahroud-Sabzevar Highway (SSH), in Semnan Province.
      Because of the extremely small population of cheetahs and the corresponding
      difficulty of finding statistically-significant clusters, we propose that every
      single cheetah-vehicle collision should be considered important. We further
      recommend that wildlife underpasses and associated fencing be constructed in
      areas of previous cheetah-vehicle collisions.

PMID- 30300598
TI  - Human Cooperation: The Hunter-Gatherer Puzzle.
AB  - In tracing the roots of human cooperation, researchers have gleaned insights from
      the sociality of contemporary hunter-gatherers. A new study among the Hadza, one
      of the few surviving foraging populations, challenges popular approaches to
      cooperation while suggesting a central role for cultural transmission.

PMID- 30300599
TI  - Plant Physiology: One Way to Dump Salt.
AB  - Soil salinization is a major challenge to global food security. The quinoa plant
      tolerates saline conditions by dumping excess salt into specialised bladder cells
      on the leaves. The pathways and transporters underlying this one-way accumulation
      system are now becoming clearer.

PMID- 30300600
TI  - Animal Behavior: Socializing Octopus.
AB  - Building on the recently published Octopus bimaculoides genome, a new study
      identifies an evolutionarily conserved neural mechanism for serotonergic
      regulation of social behaviors.

PMID- 30300601
TI  - Mutation Rates: Simpler Than We Thought?
AB  - Mutation rate variation is often explained by varying optimal rates, or through
      effective population sizes determining the effectiveness of selection. But a rate
      difference between humans and owl monkeys is now explained mechanistically as a
      consequence of differing reproductive longevities.

PMID- 30300602
TI  - Selective Attention: A Plausible Mechanism Underlying Confirmation Bias.
AB  - Our perception is strongly influenced by our experience of past stimuli and
      choices. A new study suggests that our attention is selectively deployed to those
      aspects of the sensory evidence which are consistent with our previous decisions,
      thus introducing a confirmation bias.

PMID- 30300603
TI  - Nervous System Development: Flies and Worms Converging on Neuron Identity
      Control.
AB  - Distinct neuronal cell types display phenotypic similarities such as their
      neurotransmitter identity. Studies in worms and flies have revealed that this
      phenotypic convergence can be brought about by distinct transcription factors
      regulating the same effector genes in different neuron types.

PMID- 30300604
TI  - Neuroscience: Modeling the Brain on Acid.
AB  - A receptor map of serotonin distribution is integrated into a model of the
      dynamic activity of the brain under the effects of LSD. The approach opens new
      avenues to understand experimental manipulations of healthy brain activity and
      offers a novel drug-discovery platform.

PMID- 30300605
TI  - Dinosaurs: Four Legs Good, Two Legs Bad.
AB  - The quadrupedal Sauropods - the biggest dinosaurs to walk the Earth - evolved
      from bipedal ancestors. Two new early sauropodomorphs from South Africa and
      Argentina indicate that very large, flexed-limbed sauropodomorphs coexisted with
      early columnar-limbed sauropods for 20 million years.

PMID- 30300606
TI  - Lingering Effects of Herbivory and Plant Defenses on Pollinators.
AB  - In order to survive and reproduce, flowering plants must balance the conflicting
      selective pressures of herbivore avoidance and pollinator attraction. Links
      between herbivory and reproduction are often attributed to indirect effects of
      leaf damage on pollination via reductions in floral allocation, or increases in
      chemical defenses on herbivore-damaged plants. However, the impacts of herbivory
      on pollinators have the potential to extend beyond initial floral visits when
      plant defenses impact pollinator health, foraging behavior, and reproductive
      success. Here, we examine important but underexplored ways in which herbivory may
      alter floral phenotype and thus impact pollinators. First, we outline genetic and
      biochemical mechanisms predicted to underlie floral changes following herbivory,
      as they impact the floral resources (nectar and pollen) sought by pollinators.
      Next, we discuss how the consumption of secondary compounds might impact
      pollinator fitness, including carryover effects on subsequent foraging, mating
      success, and transgenerational effects on offspring. We consider how pollinator
      health, life history, and coevolutionary history might result in context
      dependent impacts of plant defensive chemistry on pollinator fitness. Finally, we
      call for studies that measure the impact of herbivore-induced plant defenses on
      the full spectrum of flower visitors, and contrast case studies on conventional
      pollinators (for example, generalized bees) versus insects whose larvae are
      herbivores on the same plants that adults pollinate (such as several butterflies
      and moths). By linking these consequences of herbivory to fitness effects on both
      herbivores and pollinators, we will better understand how coevolution between
      plants, herbivores, and pollinators shapes both defensive and reproductive plant
      traits.

PMID- 30300607
TI  - The role of the laboratory in the expanding field of neuroimmunology:
      Autoantibodies to neural targets.
AB  - Accelerated identification of autoantibodies associated with previously
      idiopathic neurological disease has provided insights into disease mechanisms,
      enhanced understanding of neurological function, and opportunities for improved
      therapeutic interventions. The role of the laboratory in the expanding field of
      neuroimmunology is critical as specific autoantibody identification provides
      guidance to clinicians in diagnosis, prognosis, tumor search strategies, and
      therapeutic interventions. The number of specific autoantibodies identified
      continues to increase and newer testing strategies increase efficiencies in the
      laboratory and availability to clinicians. The need for broadly targeted
      efficient testing is underscored by the variability in clinical presentation and
      tumor associations attributable to a specific autoantibody, and conversely the
      various autoantibody specificities that can be the cause of a given clinical
      presentation. While many of the antineural antibodies were first recognized in
      the setting of neoplastic disease, idiopathic autoimmune neurological disease in
      the absence of underlying tumor is increasingly recognized. Appropriation of
      therapeutic modalities used to treat autoimmune disease to treat these
      autoantibody mediated neurological diseases has improved patient outcomes.
      Interaction between clinicians and laboratorians is critical to our understanding
      of these diseases and optimization of the clinical benefits of our increasing
      knowledge in neuroimmunology.

PMID- 30300608
TI  - Detection and identification of potential transglutaminase 2 substrates in the
      mouse renal glomeruli.
AB  - The glomerulus primarily comprises mesangial cells, glomerular microvascular
      endothelial cells, and podocytes. IgA nephropathy is the most common primary
      glomerulonephritis worldwide and has a risk of progression to end-stage renal
      disease. IgA nephropathy is characterized by predominant IgA deposition in the
      glomerular mesangial area, where TG2 is significantly enhanced. Therefore,
      identification of glomerular TG2 substrates is the first step in elucidating the
      role of TG2 as a crosslinking enzyme during disease progression. To clarify
      potential glomerular TG2 substrates, and to establish a procedure for substrate
      identification, we attempted to identify those molecules using normal mouse
      glomeruli. Extracts from mouse glomerular and non-glomerular fractions were
      treated with our established biotin-labeled substrate peptide, which specifically
      crosslinks to the lysine-donor substrates depending on TG2 activity. Peptide
      incorporated proteins were then purified using avidin resin and identified via
      mass spectrometry. In parallel, we performed the identification using
      corresponding samples from TG2 knockout mice. Consequently, potential TG2
      substrates were separately identified in glomerular and non-glomerular fractions.
      They were mainly identified as novel TG2 substrates and partly include the well
      known substrates. These results potentially provide novel insights into the
      mechanism underlying IgA nephropathy and may help elucidate the physiological
      functions of TG2.

PMID- 30300609
TI  - Expansion of Myeloid-Derived Suppressor Cells in the Peripheral Blood and
      Lesional Skin of Cutaneous Lupus Patients.

PMID- 30300610
TI  - Neuroendocrine stress response is moderated by sex and sex hormone receptor
      polymorphisms.
AB  - Sex hormones are significant regulators of stress reactivity, however, little is
      known about how genetic variation in hormone receptors contributes to this
      process. Here we report interactions between biological sex and repeat
      polymorphisms in genes encoding sex hormone receptors, and their effects on
      salivary cortisol reactivity in a sample of 100 participants (47 men & 53 women;
      24.7 +/- 3.23 years). Three genes were investigated: estrogen receptors alpha
      (ESR1) and beta (ESR2), and the androgen receptor (AR). Participants were
      classified as carrying 'Short' or 'Long' alleles based on median splits of the
      repeat distribution for each gene. Measures of physiological reactivity were
      collected before and after exposure to a canonical laboratory stressor and
      converted to traditional summary measures for analyses. Overall, men exhibited
      greater cortisol (p = 0.001) and mean arterial pressure reactivity (p = 0.002),
      while women displayed elevated heart rate throughout the session (p = 0.02). The
      effect of polymorphisms on salivary cortisol was sex sensitive. ESR1 was
      associated with differential reactivity in men (p = 0.04), but not women (p =
      0.24). ESR2 genotype interacted with sex such that each additional 'Long' allele
      was associated with a 6.4% decrease in salivary cortisol in men, but a 9.5%
      increase in the levels of women (p = 0.02 for interaction). For the X-linked AR,
      the 'Long' allele was associated with decreased cortisol levels in men (p =
      0.047), but in women had no effect (p = 0.75). Together, these results provide
      evidence for the saliency of genetic variation in sex hormone receptors on stress
      reactivity in humans and highlight their important role as mediators of hormonal
      activity.

PMID- 30300611
TI  - Features of Immune Cells and the Tumor-Associated Stroma Tango as Prognostic
      Factors in Patients With Pancreatic Ductal Adenocarcinoma.

PMID- 30300612
TI  - Gastroenterology's Improvements and New Features.

PMID- 30300613
TI  - Organized Screening Is Better Than Opportunistic Screening at Decreasing the
      Burden of Colorectal Cancer in the United States.

PMID- 30300614
TI  - The Unfolding Story of ATF6, Microbial Dysbiosis, and Colorectal Cancer.

PMID- 30300615
TI  - How to Promote the Academic Success of Junior Faculty Physicians in
      Gastroenterology.

PMID- 30300617
TI  - Teach Your Children Well.

PMID- 30300618
TI  - Mentorship: An Essential Element in Oral and Maxillofacial Surgery Education.

PMID- 30300619
TI  - Matrix metalloproteinases promote fat body cell dissociation and ovary
      development in Bombyx mori.
AB  - Matrix metalloproteinases (Mmps) are pivotal extracellular proteinases
      participating in tissue remodeling. Three Mmps genes have been identified from
      the silkworm, Bombyx mori, and their expression levels and enzyme activity are
      consistent with progressive fat body cell dissociation during the early pupal
      stages. Using both loss-of-function and gain-of-function experiments, we have
      demonstrated that Mmps are functionally required for fat body cell dissociation
      and ovary development in female pupae. Moderate inhibition of Mmps activity via
      inhibitor treatments delayed fat body cell dissociation and ovary development,
      while severe inhibition blocked these developmental processes and eventually led
      to pupal lethality. Individual RNAi knockdown of each Mmp delayed fat body cell
      dissociation, with the strongest and weakest phenotypes occurring for Mmp3 and
      Mmp1, respectively. By contrast, overexpression of each Mmp promoted fat body
      cell dissociation and ovary development, with the strongest stimulatory effects
      for Mmp3 overexpression and the weakest effects for Mmp1 overexpression. This is
      the first time to show that Mmps induce fat body cell dissociation in
      Lepidoptera, and we also hypothesize that Mmps-induced fat body cell dissociation
      is required for ovary development in this insect species.

PMID- 30300620
TI  - Mechanistic Study of Belinostat Oral Absorption From Spray-Dried Dispersions.
AB  - Spray-dried dispersions (SDDs) are an important technology for enhancing the oral
      bioavailability of poorly water-soluble drugs. To design an effective oral SDD
      formulation, the key rate-determining step(s) for oral drug absorption must be
      understood. This work combined in vivo and in vitro tests with in silico modeling
      to identify the rate-determining steps for oral absorption of belinostat SDDs
      made with 3 different polymers (PVP K30, PVP VA64, and HPMCAS-M). The goal was
      developing a belinostat SDD formulation that maximizes oral bioavailability
      (ideally matching the performance of a belinostat oral solution) and defining
      critical performance attributes for formulation optimization. The in vivo
      pharmacokinetic study with beagle dogs demonstrated that 1 of the 3 SDDs (PVP K30
      SDD) matched the performance of the oral solution. In vitro data coupled with in
      silico modeling elucidated differences among the SDDs and supported the
      hypothesis that absorption of belinostat in the small intestine from the other 2
      SDDs (PVP VA64 and HPMCAS-M) may be limited by dissolution rate or reduced drug
      activity (maximum concentration) in the presence of polymer. It was concluded
      that drug concentration in the stomach before emptying into the proximal
      intestine is a key factor for maximizing in vivo performance.

PMID- 30300621
TI  - Changes in the Solid State of Nicergoline, a Poorly Soluble Drug, Under Different
      Grinding and Environmental Conditions: Effect on Polymorphism and Dissolution.
AB  - Nicergoline native crystals (Form I) were subjected to different grinding methods
      for 15, 30, 45, and 60 min: Method A, grinding at 20 degrees C under air
      atmosphere; Method B, grinding in presence of liquid nitrogen under air
      atmosphere; Method C, grinding at 20 degrees C under nitrogen atmosphere; and
      Method D, grinding in presence of liquid nitrogen under nitrogen atmosphere.
      Scanning electron microscopy, differential scanning calorimetry, X-ray powder
      diffractometry, thermogravimetry, and infrared spectroscopy were used to follow
      changes in the particle size and in crystalline structures. Batches from Methods
      A and C underwent partial amorphization immediately after grinding; Form II was
      obtained by heating these partially amorphous forms or after spontaneous
      crystallization after 1 and 5 months storage. Method B promoted the hydration of
      nicergoline to a monohydrate form. Batch D was stable under grinding and neither
      amorphization nor hydration were observed. The best intrinsic dissolution rate
      was that of metastable Form II, followed by Form I, while the worst was that of
      the Method B monohydrate form. The slowest particle dissolution was observed for
      hydrated particles, because of the lowest IDR, while the most rapid was exhibited
      by batch D, because of the very small particle size.

PMID- 30300622
TI  - Skin secretion transcriptome remains in chromatographic fractions suitable for
      molecular cloning.
AB  - Traditional sources of mRNA for molecular cloning on amphibian skin secretion
      studies have been the frog's skin and skin secretions. Here, we demonstrate that
      mRNA isolated from chromatographic fractions of skin secretions is amenable for
      molecular cloning assays. We identified precursor sequences of the Arg0, Trp5,
      Leu8-bradykinin and six antimicrobial peptides of Pelophylax esculentus
      (Ranidae). These results show that both transcriptomic and peptidomic analyses
      can be performed with a single sample reducing in half the amount of starting
      skin secretion required. This is a significant advantage when working with
      endangered or very rare amphibian species, where minimal samples are available.

PMID- 30300623
TI  - Uncured PDMS inhibits myosin in vitro motility in a microfluidic flow cell.
AB  - The myosin motor powers cardiac contraction and is frequently implicated in
      hereditary heart disease by its mutation. Principal motor function
      characteristics include myosin unitary step size, duty cycle, and force-velocity
      relationship for translating actin under load. These characteristics are
      sometimes measured in vitro with a motility assay detecting fluorescent labeled
      actin filament gliding velocity over a planar array of surface immobilized
      myosin. Assay miniaturization in a polydimethylsiloxane/glass (PDMS/glass) hybrid
      microfluidic flow channel is an essential component to a small sample volume
      assay applicable to costly protein samples however the PDMS substrate
      dramatically inhibits myosin motility. Myosin in vitro motility in a PDMS/glass
      hybrid microfluidic flow cell was tested under a variety of conditions to
      identify and mitigate the effect of PDMS on myosin. Substantial contamination by
      unpolymerized species in the PDMS flow cells is shown to be the cause of myosin
      motility inhibition. Normal myosin motility recovers by either extended cell
      aging (~20 days) to allow more complete polymerization or by direct chemical
      extraction of the unpolymerized species from the polymer substrate. PDMS flow
      cell aging is the low cost alternative compatible with the other PDMS and glass
      modifications needed for in vitro myosin motility assaying.

PMID- 30300624
TI  - Managing normal tension glaucoma by lowering the intraocular pressure.

PMID- 30300625
TI  - Intraocular pressure-independent management of normal tension glaucoma.

PMID- 30300626
TI  - Chrysophanol selectively represses breast cancer cell growth by inducing reactive
      oxygen species production and endoplasmic reticulum stress via AKT and mitogen
      activated protein kinase signal pathways.
AB  - Breast cancer is a leading lethal gynecological cancer. Although many tumor
      markers and target genes have been studied in breast cancer, its incidence is
      increasing. Recently, the therapeutic effects of natural phytochemicals have been
      studied in various cancers as adjuvants. Chrysophanol is an anti-inflammatory,
      anti-angiogenetic, and anti-tumor anthraquinone but has not been widely studied
      in cancers. Here, we verified the anti-cancer effects and cellular mechanism of
      chrysophanol in human breast cancer cells (BT-474 and MCF-7). Chrysophanol
      selectively inhibited cell proliferation and induced apoptosis of breast cancer
      cells but not of normal mammary ductal epithelial cells, MCF-12A. Additionally,
      chrysophanol increased loss of mitochondrial membrane potential and cytosolic
      calcium levels to activate pro-apoptotic proteins, Bax, Bak, and cytochrome c, in
      both cell lines. Reactive oxygen species (ROS) overproduction by chrysophanol
      resulted in endoplasmic reticulum (ER) stress, leading to an increase in PERK,
      eIF2alpha, GADD153, and IRE1alpha levels in BT-474 and MCF-7 cells. These ER
      stress proteins increased by chrysophanol were repressed by co-treatment with N
      acetyl-L-cysteine, an ROS inhibitor. Western blotting showed that chrysophanol
      down-regulated ERK1/2, AKT, P70S6K, and S6 in both cell lines. However, P38 and
      JNK activities decreased in BT-474 cells and increased in MCF-7 cells.
      Additionally, co-treatment with ERK1/2 (U0126) or an AKT inhibitor (LY294002)
      plus chrysophanol reduced cell proliferation, whereas P38 (SB203580) and a JNK
      inhibitor (SP600125) showed synergic effects only in BT-474 cell lines. These
      results show that chrysophanol has anti-cancer effects on human breast cancer
      cells, specifically through mitochondrial apoptosis and ER stress induction.

PMID- 30300627
TI  - Transitional Care Interventions for Heart Failure: What Are the Mechanisms?

PMID- 30300628
TI  - Team-Based Primary Care for the Multimorbid Patient: Matching Complexity With
      Complexity.

PMID- 30300629
TI  - The saprophytic fungus Fusarium solani increases the insecticidal efficacy of the
      entomopathogenic nematode Steinernema diaprepesi.
AB  - In two field surveys, high proportions of Galleria mellonella L. (Lepidoptera:
      Pyralidae) sentinel larval cadavers were infected by Fusarium solani without
      evidence of concomitant entomopathogenic nematode (EPN) or entomopathogenic
      fungus (EPF) reproduction. Because F. solani is not considered entomopathogenic,
      the survey suggested the possibility that F. solani competes with EPNs. We tested
      the hypotheses that F. solani attracts the EPN, Steinernema diaprepesi, to
      facilitate infection of Diaprepes root weevils (Diaprepes abbreviatus L.) and
      thereafter competes with the nematode in the insect cadaver. In two-choice
      olfactometer assays where one side was treated with F. solani mycelia and
      conidia, juvenile S. diaprepesi were attracted to the fungus, in either raw soil,
      or in autoclaved soil in the presence or absence of insects. However, this
      attraction was attenuated as the habitat became more complex, by using raw soil
      in combination with insect larvae. Fusarium oxysporum did not recruit the
      nematode. When soil microcosms were tested with F. solani conidia and S.
      diaprepesi, the concomitant infection increased the mortality of the insect (P =
      0.02) to 83%, compared to 58% and 0% mortality when nematodes or fungi were
      individually applied, respectively. Concomitant inoculation also increased the
      number of cadavers that supported nematode reproduction and increased the
      population density of fungus in soil. The number of IJs entering the host insect
      was not affected by F. solani. These results support the possibility that F.
      solani can facilitate the insecticidal efficiency of S. diaprepesi in order to
      exploit the resources in the cadaver.

PMID- 30300630
TI  - Synergistic effects of pathogen and pesticide exposure on honey bee (Apis
      mellifera) survival and immunity.
AB  - Declines in native insect pollinator populations and substantial losses in
      managed honey bees have been reported on a global scale and become a widespread
      concern because of the importance of these insects for human food production and
      ecosystem stability. Several potential factors have been studied as possible
      causes of declining pollinator health, such as parasites and pathogens, exposure
      to agricultural pesticides, habitat loss and/or climate change. More recently, a
      combination of these factors rather than a single cause have been blamed for
      observed pollinator losses, but field studies of such interactions are
      challenging, especially in the presence of confounding environmental stressors.
      We therefore examined the impact of single and combined stressors on the honey
      bee (Apis mellifera) in a generally healthy Australian population. We exposed
      workers during their larval development and drones until they reached sexual
      maturity to the neonicotinoid pesticide Thiamethoxam, at concentrations more than
      20 times lower than we initially measured in the field, the microsporidian gut
      pathogen Nosema apis or both stressors at the same time. We found that
      simultaneous exposure significantly reduced bee health. We observed a substantial
      increase in mortality and a reduction of immunocompetence in workers exposed to
      both the pathogen and the pesticide. We conclude that the exposure of generally
      healthy bees to multiple environmental stressors results in synergistic effects
      where the effects are expected to negatively impact performance and could be
      sufficient to trigger colony collapse. We found that the vast majority of males
      did not survive to sexual maturity after exposure to very low levels of
      Thiamethoxam. This would not only reduce the reproductive success of individual
      colonies, but can also impact gene flow and genetic diversity at the population
      level, which are both known as key components of honey bee health.

PMID- 30300631
TI  - Molecular and structural assessment of microsporidia infecting daphnids: The
      "obtusa-like" microsporidia, a branch of the monophyletic Agglomeratidae clade,
      with the establishment of a new genus Conglomerata.
AB  - Microsporidia (Opisthosporidia, Microsporidia) are frequent parasites of
      planktonic cladocerans, including Daphnia (Crustacea, Branchiopoda). Analysis of
      available molecular data (ITS region and partial ssu and lsu rDNA) of these
      parasites indicates that many microsporidia infecting daphnids have a common
      ancestor and represent a large clade, which splits during evolution into a number
      of well supported subclades. These subclades are cytologically different but may
      be most conveniently characterised by their specific ITS barcode. We have
      analysed one of these subclades and we describe a new microsporidian genus and
      species combination, and assemble a large group of structurally indistinguishable
      microsporidian parasites that infect adipose cells of their hosts and form
      pyriform spores of a certain type ("obtuse spores"). Obtuse spores are non
      infectious by feeding to their crustacean hosts and it is plausible that
      microsporidia forming them actually are parasites of insects with aquatic larval
      stages, with an obligate two-host life cycle, analogous to the Amblyospora life
      cycle involving copepods and mosquitoes.

PMID- 30300632
TI  - Clinical Utility of Prostate and Tumor Volume-Related Parameters Following
      Radical Prostatectomy for Localized Prostate Cancer.
AB  - PURPOSE: To evaluate whether prediction of biochemical recurrence (BCR) after
      radical prostatectomy (RP) is enhanced by any of six parameters: prostate volume,
      total tumor volume (TV), high grade TV, ratio of high grade TV to TV, ratio of TV
      to prostate volume and/or ratio of high grade TV to prostate volume. MATERIALS
      AND METHODS: 1261 patients who underwent RP over a 3 year period had tumor maps
      constructed with Gleason pattern denoted as either low (3) or high (4 or 5) and
      volumetric data generated using commercially available software. Univariate Cox
      regression models were used to assess whether each volume-related parameters was
      associated with BCR after RP. A multivariable Cox regression "base model" (age,
      PSA, Gleason score/grade group, pathologic stage and margin status) was compared
      with 6 additional models (base model + each volume-related parameter) to evaluate
      enhancement in predictive accuracy. Decision curve analysis was performed to
      determine the clinical utility of parameters that enhanced predictive accuracy.
      RESULTS: On univariate analysis, each parameter was significantly associated with
      BCR except prostate volume. Predictive accuracy of multivariable base model was
      high (c-index=0.861). Adding volume-related parameters marginally enhanced
      discrimination. Decision curve analysis failed to show added benefit even for
      high grade TV/TV (parameter with highest discriminative improvement).
      CONCLUSIONS: Tumor volume-related parameters are significantly associated with
      BCR, but do not add important discrimination to standard clinicopathologic
      variables for BCR prediction nor provide benefit across a range of clinically
      relevant decision thresholds. Volume-related measurement is not warranted in
      routine pathologic evaluation and reporting.

PMID- 30300633
TI  - Making a Case for NOT Prescribing Antimuscarinic Drugs to Treat Overactive
      Bladder in Older Adults.

PMID- 30300634
TI  - Ventral pallidal modulation of aversion processing.
AB  - Responding to aversive and rewarding stimuli is essential to survival. The
      ventral pallidum (VP) is a critical node in the mesolimbic network, being the
      primary output of the nucleus accumbens and projecting to the lateral habenula
      (LHb) and ventral tegmental area (VTA). The VP is thus poised to modulate the
      habenula-tegmental circuitry and contribute to processing both rewarding and
      aversive stimuli. Here, we integrate human functional imaging, behavioral
      pharmacology in rodents, and recent optogenetic circuit dissection studies of the
      VP with a focus on the role of the neurochemically-distinct subpopulations in
      aversion processing. These recent results support a model in which glutamatergic
      VP neurons play a unique role in aversion processing, while canonical GABAergic
      VP neurons promote reinforcement and encode the hedonic value of reward. Genetic
      ablation of glutamatergic, but not GABAergic VP neurons abolishes devaluation of
      natural reward (sucrose) by pairing with an aversive stimulus (lithium chloride
      injection). Both of these populations modulate activity throughout the LHb and
      VTA, which is necessary for expression of adaptive behavior in response to
      rewarding or aversive stimuli. Future work will address how neuromodulators such
      as endogenous opioids or dopamine shape function and plasticity within these
      distinct populations of VP neurons, when these subpopulations are engaged during
      learning responses to rewarding and aversive stimuli, and how their activity is
      altered in models of reward-related disorders. Answering these questions will be
      necessary to understand the basis and ultimately develop targeted therapies for
      disorders of reward/aversion processing, such as affective, chronic pain and
      substance use disorders.

PMID- 30300635
TI  - Dopamine signals related to appetitive and aversive events in paradigms that
      manipulate reward and avoidability.
AB  - Using environmental cues to acquire good and avoid harmful things is critical for
      survival. Rewarding and aversive outcomes both drive behavior through
      reinforcement learning and sometimes occur together in the environment, but it
      remains unclear how these signals are encoded within the brain and if signals for
      positive and negative reinforcement are encoded similarly. Recent studies
      demonstrate that the dopaminergic system and interconnected brain regions process
      both positive and negative reinforcement necessary for approach and avoidance
      behaviors, respectively. Here, we review these data with a special focus on
      behavioral paradigms that manipulate both expected reward and the avoidability of
      aversive events to reveal neural correlates related to value, prediction error
      encoding, motivation, and salience.

PMID- 30300636
TI  - A competitive model for striatal action selection.
AB  - The direct and indirect pathway striatal medium spiny neurons (dMSNs and iMSNs)
      have long been linked to action selection, but the precise roles of these neurons
      in this process remain unclear. Here, we review different models of striatal
      pathway function, focusing on the classic "go/no-go" model which posits that
      dMSNs facilitate movement while iMSNs inhibit movement, and the "complementary"
      model, which argues that dMSNs facilitate the selection of specific actions while
      iMSNs inhibit potentially conflicting actions. We discuss the merits and
      shortcomings of these models and propose a "competitive" model to explain the
      contribution of these two pathways to behavior. The "competitive" model argues
      that rather than inhibiting conflicting actions, iMSNs are tuned to the same
      actions that dMSNs facilitate, and the two populations "compete" to determine the
      animal's behavioral response. This model provides a theoretical explanation for
      how these pathways work together to select actions. In addition, it provides a
      link between action selection and behavioral reinforcement, via modulating
      synaptic strength at inputs onto dMSNs and iMSNs. Finally, this model makes
      predictions about how imbalances in the activity of these pathways may underlie
      behavioral traits associated with psychiatric disorders. Understanding the roles
      of these striatal pathways in action selection may help to clarify the neuronal
      mechanisms of decision-making under normal and pathological conditions.

PMID- 30300637
TI  - Evaluation of performance monitoring ERPs through difficulty manipulation in a
      response-feedback paradigm.
AB  - Performance monitoring is an amply studied function, since it is of major
      importance in carrying out actions in our everyday life. No consensus has been
      reached on the functional role and the relationship between each event-related
      potential (ERP) characterizing this function. In this study, we used a modified
      version of the flanker task, measuring the impact of task difficulty on the
      amplitudes of response-locked and feedback-locked performance monitoring ERPs in
      a single trial. We observed a functional differentiation between fronto-central
      (ERN/CRN and FRN) and centro-parietal (Pe/Pc and P300) components: the former
      seem to be only sensitive to accuracy, whereas the latter seem to be mainly
      modulated by task difficulty. The use of a surface Laplacian transformation,
      estimating current source density, on our data also supported an effect of
      difficulty on centro-parietal response-locked and feedback-locked ERPs. This
      technique allowed the spatial resolution to be improved and provided clarity,
      associated with the difficulty manipulation, and the activity of response-locked
      and feedback-locked performance monitoring ERPs.

PMID- 30300638
TI  - Uniportal Lung Cancer Surgery: The State of the Evidence.
AB  - BACKGROUND: Uniportal video-assisted thoracic surgery (VATS) has generated much
      attention in recent years, but questions remain regarding the adequacy of
      evidence to support its use in lung cancer surgery. This review aims to explore
      what the currently published literature suggests the role of the uniportal
      approach may be, and to critically appraise that literature. METHODS: A
      systematic review was conducted using the OVID Medline database to identify
      articles related to uniportal VATS. Articles were selected for review on the
      basis of ability to provide original clinical data on the role of uniportal VATS
      for lung cancer surgery. RESULTS: Literature searching reveals that only a
      minority of the publications on uniportal VATS provide original clinical data.
      Twenty-two articles were selected for review, including 9 case series and 13
      comparative studies. No concerns about the safety of the uniportal VATS have been
      noted. Some but not all comparative studies provide data suggesting that
      uniportal VATS may hold advantages over multiportal VATS in some simple clinical
      outcomes (such as reduced lengths of stay and post-operative pain). However, the
      quantity and quality of the evidence thus far is limited. CONCLUSIONS: It remains
      premature to declare superiority for uniportal VATS in lung cancer surgery. A
      higher level of evidence is needed, especially in investigating objective
      benefits and treatment efficacy of the single incision approach.

PMID- 30300639
TI  - The incidence of patient-prosthesis mismatch is improving, but can we do even
      better?

PMID- 30300640
TI  - Off-Pump versus On-Pump Impact: Diabetic Patient Five-Year Coronary Artery Bypass
      Clinical Outcomes (Commentary).

PMID- 30300641
TI  - Intensity of Glycemic Control Affects Long-Term Survival After Coronary Artery
      Bypass Graft Surgery (Commentary).

PMID- 30300642
TI  - Two ventricles are not better than one in the Fontan circulation: equivalent late
      outcomes.
AB  - BACKGROUND: A subset of Fontan patients has two adequate-sized ventricles, but an
      anatomic biventricular circulation cannot be achieved due to complex morphology
      or technical reasons. We sought to determine whether these two-ventricle Fontan
      patients had superior outcomes compared to those with a single ventricle.
      METHODS: A bi-national Registry of Fontan patients (n=1377) was analysed to
      identify Fontan patients with two adequate ventricles. This cohort was compared
      with single ventricle Fontan patients. The primary end-point was a composite
      endpoint called 'Fontan failure' encompassing death, transplant, Fontan takedown
      or conversion, protein-losing enteropathy, plastic bronchitis or NYHA III or IV
      functional class. RESULTS: A total of 79 Fontan patients with two adequate
      ventricles (2V) were compared with 1291 single ventricle (1V) Fontan patients.
      Median follow-up for the entire cohort was 11.5 years (IQR 5.1-18.8 years). There
      was no difference in unadjusted 15-year freedom from Fontan failure (2V: 81% (95%
      CI 69-94%) vs. 1V: 86% (83-88%), p= 0.4). Propensity-score matching for potential
      confounding factors yielded 75 two-ventricle Fontan patients being matched with
      604 single ventricle Fontan patients, in which 15-year freedom from Fontan
      failure was also not different (2V: 79% (67-94%) vs 1V: 87% (84-91%), p=0.3).
      CONCLUSIONS: The two-ventricle Fontan circulation does not have better outcomes
      compared to the single ventricle Fontan. Late outcomes may depend more on other
      characteristics of the Fontan circulation. This finding is relevant when the
      Fontan procedure is being considered as an alternative to anatomic repair in
      complex two ventricle morphologies.

PMID- 30300643
TI  - Methylene Blue for Vasoplegic Syndrome After Cardiac Operations.

PMID- 30300644
TI  - Surgical atrial fibrillation ablation improves long-term survival: A multicenter
      analysis.
AB  - BACKGROUND: Society of Thoracic Surgeons guidelines recommend surgical ablation
      (SA) at the time of concomitant mitral operations, aortic valve replacement,
      coronary artery bypass grafting (CABG), and AVR plus CABG for patients in atrial
      fibrillation (AF). The goal of this analysis was to assess the influence of SA on
      long term survival. METHODS: A retrospective analysis of 20,407 consecutive CABG
      or valve procedures from 2008-2015 among 7 centers reporting to a prospectively
      maintained clinical registry was conducted. Patients undergoing surgery with
      documented pre-operative AF were included (n=2,740). Patients receiving SA were
      compared to those receiving no SA. The primary endpoint was all-cause mortality.
      Secondary endpoints included in-hospital morbidity and mortality. RESULTS: The
      frequency of SA was 23.1% (n=634), and there was an increase in the rate of SA
      over the study period (p<0.001). Concomitant SA was performed in: 16.2% of CABG,
      30.6% of valve, and 24.3% of valve plus CABG cases. There was a significant
      improvement in unadjusted survival among patients undergoing SA (HR 0.54,
      95%CI=0.42-0.70). Moreover, there were no differences in post-operative
      complications. SA patients did have longer bypass times (p<0.001) but a shorter
      overall length of stay (p<0.001). After risk adjustment, SA patients had an
      improved 5-year survival (HR 0.69, 95%CI=0.51-0.92), and the effect was observed
      across all operations. CONCLUSIONS: In a multi-center cohort of patients with AF,
      concomitant SA resulted in significantly improved long-term survival across CABG,
      valve, and valve plus CABG patients. These findings support current STS
      guidelines recommending broader application of concomitant SA.

PMID- 30300645
TI  - LMIC and US trainees benefit from the global health educator.

PMID- 30300646
TI  - Obesity Paradox in Esophageal Cancer: Fashion or Reality? (Reply).

PMID- 30300647
TI  - The evolution of variance in sequential defences.
AB  - The defences used by organisms against predators display a great degree of
      variability. Defence phenotypes can differ substantially among individuals of the
      same species, and a single individual can itself deploy a variety of defences.
      Here, we use a mathematical model that includes mutation and selection to
      understand the evolutionary origin of this variability in a population of a
      species that deploys defences sequentially ("first" and "second" defences).
      Typically, the first defence evolves to have lower variance, i.e. appears more
      closely accumulated around the ideal phenotype, than the second defence (even
      when the breaching the first defence incurs more fitness loss than breaching the
      second defence with the other parameters the same for both defences). However, if
      the first defence is much less effective in repelling predators, or is much less
      tolerant of deviation from the ideal phenotype, then the first defence can evolve
      to have higher variance than the second. Other factors like mutation strength and
      the losses in the fitness when each defence fails also influence the defence
      variance. Larger mutation rate incurs larger equilibrium variances, and when the
      comparative importance in fitness of one defence increases, then the ratio
      between the variances of this defence and the other defence decreases.
      Sequentially acting defences are found in many organisms, so we encourage
      empirical research to test our theoretical predictions.

PMID- 30300648
TI  - Viral replication modes in single-peak fitness landscapes: A dynamical systems
      analysis.
AB  - Positive-sense, single-stranded RNA viruses are important pathogens infecting
      almost all types of organisms. Experimental evidence from distributions of
      mutations and from viral RNA amplification suggest that these pathogens may
      follow different RNA replication modes, ranging from the stamping machine
      replication (SMR) to the geometric replication (GR) mode. Although previous
      theoretical work has focused on the evolutionary dynamics of RNA viruses
      amplifying their genomes with different strategies, little is known in terms of
      the bifurcations and transitions involving the so-called error threshold
      (mutation-induced dominance of mutants) and lethal mutagenesis (extinction of all
      sequences due to mutation accumulation and demographic stochasticity). Here we
      analyze a dynamical system describing the intracellular amplification of viral
      RNA genomes evolving on a single-peak fitness landscape focusing on three cases
      considering neutral, deleterious, and lethal mutants. We analytically derive the
      critical mutation rates causing lethal mutagenesis and error threshold, governed
      by transcritical bifurcations that depend on parameters alpha (parameter
      introducing the mode of replication), replicative fitness of mutants (k1), and on
      the spontaneous degradation rates of the sequences (epsilon). Our results relate
      the error catastrophe with lethal mutagenesis in a model with continuous
      populations of viral genomes. The former case involves dominance of the mutant
      sequences, while the latter, a deterministic extinction of the viral RNAs during
      replication due to increased mutation. For the lethal case the critical mutation
      rate involving lethal mutagenesis is MUc=1-E/alpha. Here, the SMR involves lower
      critical mutation rates, being the system more robust to lethal mutagenesis
      replicating closer to the GR mode. This result is also found for the neutral and
      deleterious cases, but for these later cases lethal mutagenesis can shift to the
      error threshold once the replication mode surpasses a threshold given by
      alpha=epsilon/k1.

PMID- 30300649
TI  - Wall stress enhanced exocytosis of extracellular vesicles as a possible mechanism
      of left-right symmetry-breaking in vertebrate development.
AB  - In certain vertebrate species, the developing embryo breaks left-right symmetry
      in a transient organising structure: the "Left-Right Organiser" (LRO) known as
      the "node" in mice, and "Kupffer's vesicle" in fish. Directional cilia-driven
      flow is integral to this symmetry-breaking process, however the mechanism by
      which this flow is translated into an asymmetric signal remains contested; the
      principal theories are either flow transport of vesicles containing morphogens,
      or flow mechanosensing by cilia. Whilst some recent work favours the morphogen
      theory, other findings seem to support mechanosensing. In this study, we consider
      a hypothesis whereby the cilia themselves drive the release of morphogen-carrying
      extracellular vesicles (EVs) into the LRO; namely, that fluid stresses on the
      cell membrane induce/enhance exocytosis of EVs. Using a mathematical model, we
      calculate significant wall normal and shear stresses for a range of typical
      cilium parameter values comparable to levels capable of enhancing exocytosis.
      This mechanism may be able to reconcile the apparently conflicting experimental
      evidence.

PMID- 30300650
TI  - Complex interaction of resource availability, life-history and demography
      determines the dynamics and stability of stage-structured populations.
AB  - The dynamics of stage-structured populations facing stage-specific variability in
      resource availability and/or demographic factors like unequal sex-ratios, remains
      poorly understood. We addressed these issues using a stage-structured individual
      based model that incorporates life-history parameters common to many
      holometabolous insects. The model was calibrated using time series data from a 49
      generation experiment on laboratory populations of Drosophila melanogaster,
      subjected to four different combinations of larval and adult nutritional levels.
      The model was able to capture multiple qualitative and quantitative aspects of
      the empirical time series across three independent studies. We then simulated the
      model to explore the interaction of various life-history parameters and
      nutritional levels in determining population stability. In all nutritional
      regimes, constancy stability of the populations was reduced upon increasing egg
      hatchability, critical mass, and proportion of body resource allocated to female
      fecundity. However, the effects of increasing sensitivity of female-fecundity to
      adult density on constancy stability varied across nutrition regimes. The effects
      of unequal sex-ratio and sex-specific culling were greatly influenced by
      fecundity but not by levels of juvenile nutrition. Finally, we investigated the
      implications of some of these insights on the efficiency of the widely-used pest
      control method, the Sterile Insect Technique (SIT). We show that increasing the
      amount of juvenile food had no effects on SIT efficiency when the density
      independent fecundity is low, but reduces SIT efficiency when the density
      independent fecundity is high.

PMID- 30300651
TI  - Sleep Timing, Stability, and BP in the Sueno Ancillary Study of the Hispanic
      Community Health Study/Study of Latinos.
AB  - BACKGROUND: Timing and stability of the sleep-wake cycle are potential modifiable
      risk factors for cardiometabolic disease. The aim of this study was to evaluate
      the relationship between objective measures of sleep-wake timing and stability
      with cardiometabolic disease risk. METHODS: In this multicenter, cross-sectional,
      population-based study, actigraphy data were obtained from the 2,156 adults, aged
      18 to 64 years, recruited from the Sueno ancillary study of the Hispanic
      Community Health Study/Study of Latinos (2010-2013). These data were correlated
      with measures of cardiometabolic disease risk, including systolic and diastolic
      BPs, homeostatic assessment of insulin resistance, glycosylated hemoglobin, BMI,
      and hypertension and diabetes status. RESULTS: Each 10% decrease in interdaily
      stability was associated with a 3.0% absolute increase in the prevalence of
      hypertension (95% CI, 0.6-5.3; P < .05), an increase in systolic BP by 0.78 mm Hg
      (95% CI, 0.12-1.45; P < .05) and an increase in diastolic BP by 0.80 mm Hg (95%
      CI, 0.28-1.32; P < .05). In addition, delaying the midpoint of sleep by 1 h was
      associated with an increase in systolic BP by 0.73 mm Hg (95% CI, 0.30-1.16; P <
      .01) and diastolic BP by 0.53 mm Hg (95% CI, 0.17-0.90; P < .01). These
      associations were not significant after adjusting for shift work status. No
      association was found between interdaily stability or sleep timing and diabetes,
      BMI, or insulin resistance. CONCLUSIONS: These results suggest that beyond sleep
      duration, the timing and regularity of sleep-wake schedules are related to
      hypertension prevalence and BP.

PMID- 30300653
TI  - Validation of the Incremental Shuttle Walk Test as a Clinical End Point in
      Bronchiectasis.
AB  - BACKGROUND: A validated clinical end point is needed to assess response to
      therapies in bronchiectasis. OBJECTIVES: The goal of this study was to assess the
      reliability, validity, and responsiveness of the incremental shuttle walk test
      (ISWT) as a clinical end point in bronchiectasis. METHODS: In clinically stable
      patients (n = 30), the ISWT was performed twice, 6 months apart. Correlation
      between the St. George's Respiratory Questionnaire (SGRQ) and the ISWT (n = 94)
      was performed. The 1-year gentamicin study was reanalyzed to assess the area
      under the curve (percent change of ISWT with a >= 4 unit improvement in total
      SGRQ). ISWT was performed prior to and following 14 days of antibiotics for an
      exacerbation (94 oral courses and 30 IV courses, n = 124) and reanalysis of the 1
      year gentamicin study (n = 57). RESULTS: The ISWT did not significantly change
      over 6 months while clinically stable. The ISWT correlated inversely with the
      SGRQ (rs = -0.60; P < .0001), Bronchiectasis Severity Index score (rs = -0.44; P
      < .0001), and sedentary time (rs = -0.48; P = .0007) but correlated with physical
      activity (rs = 0.42; P = .004). The area under the curve for percent change in
      ISWT with >= 4 unit improvement in SGRQ was 0.79 (95% CI, 0.66-0.91; P = .001). A
      threshold of 5% improvement in the ISWT had a 92% sensitivity but 50%
      specificity, and from the responsiveness studies would capture 73% of all
      patients. CONCLUSIONS: This study confirmed the ISWT to be reliable, valid, and
      responsive to change in patients with bronchiectasis. The authors propose that a
      minimum clinically important difference of 5% improvement in the ISWT would be a
      useful objective end point to assess therapies in bronchiectasis.

PMID- 30300654
TI  - Differential effects of high-fat diets before pregnancy and/or during pregnancy
      on fetal growth development.
AB  - AIMS: The aim of the study was to investigate the effects of high-fat diets
      before pregnancy and/or during pregnancy on fetal development. MAIN METHODS:
      Female mice were fed with standard diets (SD) or high-fat diets (HFD). After 12
      weeks, females were mated. In the SD + SD and HFD + SD groups, pregnant mice were
      fed with standard diets. In the SD + HFD and HFD + HFD groups, pregnant mice were
      fed with high-fat diets. All pregnant mice were sacrificed on gestational day
      (GD) 16. KEY FINDINGS: Fetal weight and crown-rump length were increased in SD +
      HFD-fed mice, whereas were decreased in HFD + SD-fed mice. The levels of CRP and
      TNF-alpha in maternal serum and amniotic fluid were elevated in all HFD-fed mice.
      Placenta weight was elevated in SD + HFD-fed but not in HFD + SD-fed mice. Blood
      sinusoid areas, and the number of Ki67-positive cells, a marker of cell
      proliferation, were elevated in placental labyrinth layer of SD + HFD-fed mice,
      but decreased in HFD + SD-fed mice. Finally, placental Fatp1, a fatty acid
      transporter gene, was up-regulated in SD + HFD-fed mice. By contrary, placental
      Fatp1, and Snat2, an amino acid transporter, were down-regulated in HFD + SD-fed
      mice. Moreover, the levels of placental FATP4 and SNAT2 were up-regulated in SD +
      HFD-fed mice. SIGNIFICANCE: HFD before pregnancy and HFD during pregnancy
      differentially disturb fetal growth development. HFD before pregnancy-induced
      fetal SGA might be partially attributed to inflammatory cytokines and mediators
      derived from maternal adipose tissue. By contrary, HFD during pregnancy-induced
      fetal overweight may be partially attributed to the increase of placental
      nutrient transport capacity.

PMID- 30300652
TI  - VTE Risk Profiles and Prophylaxis in Medical and Surgical Inpatients: The
      Identification of Chinese Hospitalized Patients' Risk Profile for Venous
      Thromboembolism (DissolVE-2)-A Cross-sectional Study.
AB  - BACKGROUND: Limited data exist on VTE risk and prophylaxis in Chinese inpatients.
      The Identification of Chinese Hospitalized Patients' Risk Profile for Venous
      Thromboembolism-2 (DissolVE-2), a nationwide, multicenter, cross-sectional study,
      was therefore designed to investigate prevalence of VTE risks and evaluate VTE
      prophylaxis implementation compliant with the latest prophylaxis guidelines
      (American College of Chest Physicians [CHEST], 9th edition). METHODS: Adults
      admitted (>= 72 h) to 60 urban, tertiary Chinese hospitals due to acute medical
      conditions or surgery from March to September 2016 were assessed for VTE risk.
      Risk assessments were made by using the Padua Prediction Scoring or Caprini Risk
      Assessment model, risk factors, and prophylaxis based on the CHEST guidelines,
      9th edition. RESULTS: A total of 13,609 patients (6,986 surgical and 6,623
      medical) were analyzed. VTE risk in surgical inpatients was categorized as low
      (13.9%; 95% CI, 13.1-14.7), moderate (32.7%; 95% CI, 31.6-33.8), and high (53.4%;
      95% CI, 52.2-54.6); risk in medical patients was categorized as low (63.4%; 95%
      CI, 62.2-64.6) and high (36.6%; 95% CI, 35.4-37.8). Major risk factors in
      surgical and medical patients were major open surgery (52.6%) and acute infection
      (42.2%), respectively. Overall rate of any prophylaxis and appropriate
      prophylactic method was 14.3% (19.0% vs 9.3%) and 10.3% (11.8% vs 6.0%) in
      surgical and medical patients. CONCLUSIONS: A large proportion of hospitalized
      patients reported VTE risk and low rate of CHEST-recommended prophylaxis. The
      data highlight the insufficient management of VTE risk and show the great
      potential for improving physicians' awareness and current practices across China.
      TRIAL REGISTRY: Chinese Clinical Trial Registry; No.: ChiCTR-OOC-16010187; URL:
      http://www.chictr.org.cn/showproj.aspx?proj=17077.

PMID- 30300655
TI  - Effect of valproic acid alone or combined with low dose gamma irradiation in
      modulating PTZ-induced convulsions in rats involving AKT/m-TOR pathway.
AB  - AIM: The current study evaluates the anticonvulsant effect of valproic acid (VPA)
      alone or combined with low dose gamma-irradiation (LDR) against pentylenetetrazol
      induced convulsions in rats. MATERIAL AND METHODS: Five groups of rats were used,
      group I served as normal control, group II served as PTZ- control and the other
      three groups were pretreated with single LDR(o.5 Gy), VPA(150 mg/kg i.p.5 days)
      and VPA with LDR respectively before PTZ injection. Racine score, latency and
      duration of convulsions were assessed. Evaluation of brain neurotransmitters
      (glutamate and GABA) as well as AKT/m-TOR pathway (protein kinase B [AKT],
      mammalian target of rapamycin [m-TOR], protein S6 and caspase 3). Measurement of
      oxidative stress (Malondialdehyde, glutathione and nitric oxide) was carried out.
      Histopathological examinations of hippocampi were done. KEY FINDINGS: PTZ
      resulted in behavioural changes (high Racine score, long seizure duration and
      short latency).PTZ enhanced oxidative stress state (high MDA and NO, as well as
      low GSH) compared to normal control. VPA alone or combined with LDR ameliorated,
      the convulsions and caused significant improvement in behavioural changes and
      other tested parameters compared to normal control. Histopathological examination
      of hippocampi was carried out to adjoin the biochemical changes. Certain changes
      were observed after PTZ injection. However, normal pictures of the other tested
      groups. SIGNIFICANCE: The previously mentioned findings support that LDR purveyed
      novel anticonvulsant activity which could offer a possible contributor in the
      basic treatment of convulsions. This effect might be due to modulation of AkT/m
      TOR pathway, reduction of oxidative stress and modulation of neurotransmitters.

PMID- 30300656
TI  - Salidroside protects LPS-induced injury in human thyroid follicular epithelial
      cells by upregulation of MiR-27a.
AB  - AIMS: Hypothyroidism is a common endocrine disease without standard treatment.
      Salidroside (SAL) has various positive biological activities. In this study,
      experiments were performed to investigate whether SAL had protective effects on
      LPS-induced cell inflammatory injury. MAIN METHODS: The human thyroid follicular
      epithelial cells (Nthy-ori 3-1) stimulated by LPS were treated with SAL and/or
      transfected with miR-27a inhibitor. Cell viability and cell apoptosis were detect
      by Cell Counting Kit-8 assay and flow cytometry, respectively. The expression of
      Cyclin D1 and apoptosis-related proteins, Notch proteins and NF-kappaB pathways
      related proteins were all measured by western blot. The expression of miR-27a and
      inflammatory chemokines MCP-1, IL-6 and TNF-alpha was examined by qRT-PCR. The
      protein weight of MCP-1, IL-6 and TNF-alpha was detected by ELISA. KEY FINDINGS:
      LPS treatment induced cell injury by decreasing cell viability, and inducing cell
      apoptosis and inflammatory chemokines MCP-1, IL-6 and TNF-alpha. In addition, SAL
      alleviated LPS-induced cell injury by increasing cell viability, and decreasing
      cell apoptosis and inflammatory chemokines MCP-1, IL-6 and TNF-alpha. SAL
      upregulated miR-27a expression and further study showed that miR-27a
      downregulation impaired the protective effects of SAL. SAL downregulated the
      expression of Notch1/2, and phosphorylation of p65 and IkappaBalpha.
      SIGNIFICANCE: SAL protects against LPS-induced injury in human thyroid follicular
      epithelial cells by upregulation of miR-27a. This process might be via
      inactivating Notch and NF-kappaB pathways.

PMID- 30300657
TI  - Pulmonary arterial input impedance reflects the mechanical properties of
      pulmonary arterial remodeling in rats with pulmonary hypertension.
AB  - AIMS: Although pulmonary arterial remolding in pulmonary hypertension (PH)
      changes the mechanical properties of the pulmonary artery, most clinical studies
      have focused on static mechanical properties (resistance), and dynamic mechanical
      properties (compliance) have not attracted much attention. As arterial compliance
      plays a significant role in determining afterload of the right ventricle, we
      evaluated how PH changes the dynamic mechanical properties of the pulmonary
      artery using high-resolution, wideband input impedance (ZPA). We then examined
      how changes in ZPA account for arterial remodeling. Clarification of the
      relationship between arterial remodeling and ZPA could help evaluate arterial
      remodeling according to hemodynamics. MAIN METHODS: PH was induced in Sprague
      Dawley rats with an injection of Sugen5416 (20 mg/kg) and 3-week exposure to
      hypoxia (10% oxygen) (SuHx). ZPA was evaluated from pulmonary artery pressure and
      flow under irregular pacing. Pulmonary histology was examined at baseline and 1,
      3, and 8 weeks (n = 7, each) after Sugen5416 injection. KEY FINDINGS: SuHx
      progressively increased pulmonary arterial pressure. ZPA findings indicated that
      SuHx progressively increased resistance (baseline: 9.3 +/- 3.6, SuHx1W: 20.7 +/-
      7.9, SuHx3W: 48.8 +/- 6.9, SuHx8W: 62.9 +/- 17.8 mm Hg/mL/s, p < 0.01) and
      decreased compliance (baseline: 11.9 +/- 2.1, SuHx1W: 5.3 +/- 1.7, SuHx3W: 2.1 +/
      0.7, SuHx8W: 1.9 +/- 0.6 * 10-3 mL/mm Hg, p < 0.01). The time constant did not
      significantly change. The progressive reduction in compliance was closely
      associated with wall thickening of small pulmonary arteries. SIGNIFICANCE: The
      finding that changes in resistance were reciprocally associated with those in
      compliance indicates that resistant and compliant vessels are anatomically
      inseparable. The analysis of ZPA might help evaluate arterial remodeling in PH
      according to hemodynamics.

PMID- 30300658
TI  - Miniaturized whole-cell bacterial bioreporter assay for identification of quorum
      sensing interfering compounds.
AB  - The continuing emergence and spread of antibiotic-resistant bacteria is worrisome
      and new strategies to curb bacterial infections are being sought. The
      interference of bacterial quorum sensing (QS) signaling has been suggested as a
      prospective antivirulence strategy. The AI-2 QS system is present in multiple
      bacterial species and has been shown to be correlated with pathogenicity. To
      facilitate the discovery of novel compounds interfering with AI-2 QS, we
      established a high-throughput setup of whole-cell bioreporter assay, which can be
      performed in either 96- or 384-well format. Agonistic or antagonistic activities
      of the test compounds against Escherichia coli LsrB-type AI-2 QS system are
      monitored by measuring the level of beta-galactosidase expression. A control
      strain expressing beta-galactosidase in quorum sensing-independent manner is
      included into the assay for false-positive detection.

PMID- 30300659
TI  - Racial and Sociodemographic Differences of Semen Parameters Among US Men
      Undergoing a Semen Analysis.
AB  - OBJECTIVE: To characterize sociodemographic differences in semen parameters among
      US men undergoing a semen analysis. MATERIALS AND METHODS: Men who provided a
      semen sample were identified from insurance claims between 2007 and 2016.
      Differences in semen parameters were characterized according to age, race,
      education, and region. Mean semen parameters and proportions of men with
      suboptimal parameters were compared and risks of oligospermia and azoospermia
      were assessed by logistic regression. RESULTS: Of the 7263 men included, most men
      were white (55.1%), Hispanic (20.2%), or Asian (10.2%). Asians had the highest
      mean semen concentrations (69.2 * 106/mL), whereas blacks had the lowest (51.3 *
      106/mL). Men from the Midwest were more likely to have oligospermia (odds ratio
      [OR] 1.62; 95% confidence interval [CI] 1.34-1.94), whereas men from the West
      were less likely (OR 0.82; 95% CI 0.82-0.94) when compared with men from South.
      An association between education and sperm concentration was observed. For
      example, men with a high school diploma or less were more likely to have
      oligospermia (OR 1.09; 95% CI 0.95-1.26), whereas men with at least a bachelor
      degree were less likely (OR 0.87; 95% CI 0.76-1.0) when compared with men with
      less than a bachelor degree. CONCLUSION: As we observed differences in semen
      quality based on sociodemographic factors, these findings may have clinical
      implications as relying on a single reference value when guiding infertile
      couples may be problematic given these variations. Further work is warranted to
      understand the etiology of such differences and determine if different normative
      reference values may apply for different populations.

PMID- 30300660
TI  - Robot-assisted Partial Nephrectomy: Is Routine Urinary Catheterization Still
      Mandatory in the Era of Enhanced Recovery?
AB  - OBJECTIVE: To assess the benefits and safety of noncatheterization during robot
      assisted partial nephrectomy within an enhanced recovery protocol. MATERIALS AND
      METHODS: A single-center retrospective comparative study was carried out of
      consecutive patients who underwent a robot-assisted partial nephrectomy between
      February 2015 and December 2017 within an early recovery program. The patients
      who received a urinary catheter were compared with those who did not in terms of
      postoperative complications, acute urinary retention rates, urinary tract
      infection rates, and lengths of hospital stay. RESULTS: Of the 145 patients who
      followed an early recovery program after robot-assisted partial nephrectomy in
      the study period, 96 received a urinary catheter and 49 did not. There was no
      significant difference between these 2 groups in terms of the rates of acute
      urinary retention (3% vs 6%, respectively; P = .393), urinary tract infection (3%
      vs 2%; P = .707), postoperative complications (14% vs 18%; P = .445), or
      readmissions within 30 days (8% vs 6%; P = .636). However, patients who did not
      receive a catheter had shorter initial and total (including readmissions) lengths
      of hospital stay (respectively 2.16 days vs 2.56 days; P = .058, and 2.27 days vs
      3.40 days; P <.001). CONCLUSION: Our findings challenge the routine use of
      urinary catheterization during robot-assisted partial nephrectomies.
      Noncatheterization does not seem to increase the risk of postoperative urinary
      retention. Only catheterizing specific at-risk patients may prove beneficial.

PMID- 30300661
TI  - The effect of countermeasures against the reaction time based concealed
      information test on the P300 index of knowledge recognition: A combined RT and
      P300-based test.
AB  - Behavioral reaction time (RT) to key (probe) stimuli in a concealed information
      test (CIT) is usually greater than RT to irrelevant stimuli, and this difference
      has been utilized as a sign of recognition of concealed information. The ability
      to voluntarily increase irrelevant RT would appear to be an obvious
      countermeasure to the RT-based CIT. This study examined the effect of such
      countermeasure use on the simultaneously recorded P300 event related potentials.
      There were two blocks of trials in the present study, based on the 3-stimulus
      protocol. On the first trial block, half the participants were tested on
      concealed recognition of their phone numbers without a countermeasure. In the
      second block, this subset of participants were tested on their birth dates, while
      they applied a countermeasure consisting of the mental statement of the phrase
      "yes sir" prior to the button press signaling irrelevant stimulus. The other half
      of the subjects received the reverse order of stimulus categories. Results were
      that probe RT exceeded irrelevant RT in the first block, but that this
      relationship was reversed on the second block. In contrast, although the probe
      P300 exceeded the irrelevant P300 in the first block, this difference
      significantly increased in the second (RT countermeasure) block, leading to more
      detections based on P300. Thus, there was a differential effect of this novel
      countermeasure (directed at countering RT) on RT and P300, which actually led to
      improved detection with P300, suggesting that both measures might be profitably
      used in field applications.

PMID- 30300662
TI  - Frontal asymmetry predicts the incentive value of perceptual information.
AB  - Information has been suggested to convey incentive value mediated by dopaminergic
      systems similar to those implicated in extrinsic reward. Although the reward
      characteristics of information have received preliminary support by behavioral
      and fMRI findings, EEG correlates and individual differences have not yet been
      examined. In the current study, a novel perceptual paradigm was developed to
      probe the associations between anticipation of perceptual information and frontal
      electroencephalographic alpha asymmetry, i.e., a marker of approach motivation.
      Assuming individual differences in engaging with perceptual information, trait
      openness was examined as a moderator of the associations. One hundred and twenty
      participants viewed partly visible photos that were gradually uncovered. After
      they indicated state levels of confidence and curiosity, the photos were fully
      disclosed. During anticipation of the fully disclosed stimuli, left-lateralized
      asymmetry linearly increased with curiosity. Moreover, a curvilinear relationship
      between confidence and left-lateralized asymmetry emerged, suggesting enhanced
      motivational activation during medium levels of uncertainty. The curvilinear
      relationship was moderated by trait openness, indicating individual differences
      in the responsiveness to perceptual uncertainty. In summary, our findings provide
      novel empirical evidence for the incentive motivational value of information.

PMID- 30300663
TI  - The aversive brain system of teleosts: Implications for neuroscience and
      biological psychiatry.
AB  - Defensive behavior is a function of specific survival circuits, the "aversive
      brain system", that are thought to be conserved across vertebrates, and involve
      threat detection and the organization of defensive responses to reduce or
      eliminate threat. In mammals, these circuits involve amygdalar and hypothalamic
      subnuclei and midbrain circuits. The increased interest in teleost fishes as
      model organisms in neuroscience created a demand to understand which brain
      circuits are involved in defensive behavior. Telencephalic and habenular circuits
      represent a "forebrain circuit" for threat processing and organization of
      responses, being important to mounting appropriate coping responses. Specific
      hypothalamic circuits organize neuroendocrine and neurovegetative outputs, but
      are the less well-studied in fish. A "midbrain circuit" is represented by
      projections to interneurons in the optic tectum which mediate fast escape
      responses via projections to the central gray and/or the brainstem escape
      network. Threatening stimuli (especially visual stimuli) can bypass the "high
      road" and directly activate this system, initiating escape responses. Increased
      attention to these circuits in an evolutionary framework is still needed.

PMID- 30300664
TI  - Expression of amino acid transporter (LAT1 and 4F2hc) in pulmonary pleomorphic
      carcinoma.
AB  - Amino acid transporters are necessary for tumor growth, metastasis, and survival
      of various neoplasms; however, the clinicopathological significance of L-type
      amino acid transporter 1 (LAT1) and 4F2 cell surface antigen (4F2hc) in patients
      with pulmonary pleomorphic carcinoma (PPC) remains unknown. The aim of this study
      is to clarify the prognostic impact of these amino acid transporters in PPC. One
      hundred and five patients with surgically resected PPC were assessed by
      immunohistochemistry. The expression of LAT1 and 4F2hc, and Ki-67 labeling index
      were investigated using specimens of the resected tumors. LAT1 and 4F2hc were
      highly expressed in 35% and 53% of all patients (n = 105, P < .01), 25% and 48%
      of patients with an adenocarcinoma component (n = 48, P = .02), and 44% and 58%
      of patients with a non-adenocarcinoma component (n = 57, P = .18), respectively.
      A high LAT1 expression was significantly related to advanced disease, lymphatic
      permeation, tumor cell proliferation and 4F2hc expression. By multivariate
      analysis, LAT1 and 4F2hc were identified as significant independent markers for
      predicting a worse prognosis. LAT1 is highly expressed in PPC and high LAT1
      expression can serve as a significant predictor linked to a worse prognosis in
      patients with PPC.

PMID- 30300665
TI  - Chronic inflammatory pain drives alcohol drinking in a sex-dependent manner for
      C57BL/6J mice.
AB  - Sex differences in chronic pain and alcohol abuse are not well understood. The
      development of rodent models is imperative for investigating the underlying
      changes behind these pathological states. In the present study, we investigated
      whether hind paw treatment with the inflammatory agent Complete Freund's Adjuvant
      (CFA) could generate hyperalgesia and alter alcohol consumption in male and
      female C57BL/6J mice. CFA treatment led to greater nociceptive sensitivity for
      both sexes in the Hargreaves test, and increased alcohol drinking for males in a
      continuous access two-bottle choice (CA2BC) paradigm. Regardless of treatment,
      female mice exhibited greater alcohol drinking than males. Following a 2-hour
      terminal drinking session, CFA treatment failed to produce changes in alcohol
      drinking, blood ethanol concentration (BEC), and plasma corticosterone (CORT) for
      both sexes. 2-hr alcohol consumption and CORT was higher in females than males,
      irrespective of CFA treatment. Taken together, these findings have established
      that male mice are more susceptible to escalations in alcohol drinking when
      undergoing pain, despite higher levels of total alcohol drinking and CORT in
      females. Furthermore, the exposure of CFA-treated C57BL/6J mice to the CA2BC
      drinking paradigm has proven to be a useful model for studying the relationship
      between chronic pain and alcohol abuse. Future applications of the CFA/CA2BC
      model should incorporate manipulations of stress signaling and other related
      biological systems to improve our mechanistic understanding of pain and alcohol
      interactions.

PMID- 30300666
TI  - Virulence genes and genetic diversity assessment of Shiga toxin-producing
      Escherichia coli O91 strains from cattle, beef and poultry products.
AB  - Shiga toxin-producing Escherichia coli (STEC) O91 has ranked in the top five of
      the non-O157 serogroups most frequently associated with human cases. In order to
      gain insight into the genetic diversity of O91 Latin American STEC strains, we
      analyzed their virulence properties and carried out a subtyping assay. A panel of
      21 virulence genetic markers associated with human and animal infections was
      evaluated and the relatedness among strains was determined by a multiple-locus
      variable-number tandem repeats analysis (MLVA) comprising 9 VNTR loci. Twenty-two
      STEC O91 isolated from cattle and meat food and belonging to 5 serotypes
      (O91:H21, O91:H8, O91:H14, O91:H28, O91:H40) were studied. Eight virulence
      profiles were obtained for the O91 STEC strains: 4 for O91:H21 plus one for
      O91:H8, O91:H14, O91:H28 and O91:H40. All strains contained ehxA and lpfA0113
      genes and only both stx1-positive strains lacked saa, which encodes the STEC
      autoagglutinating adhesin. Other genes involved in adhesion were detected: ehaA
      (91%), elfA and espP (86%), ecpA (82%) and, hcpA (77%). The gene encoding the
      cytolethal distending toxin type-V (CDT-V) was found only in O91:H8 and O91:H21,
      being present in the majority (89%) of strains of this last serotype. MLVA typing
      divided the total number of strains into 12 genotypes, and 9 of them were unique
      to a single strain. No association was observed between the virulence profiles
      and the source of the strains. Although they lack the eae gene, most of the
      strains have the genetic potential to adhere to host cells through other
      structures and possess cdt-V, which has been found in STEC strains involved in
      serious diseases. The MLVA showed clonal relatedness among strains isolated from
      cattle belonged to a same dairy farm and suggested that the same clone remains
      circulating throughout the year and, on the other hand, the need to increase the
      number of VNTR loci which could allow a higher discrimination among O91:H21
      isolates.

PMID- 30300667
TI  - Identification of key pathways and metabolic fingerprints of longevity in C.
      elegans.
AB  - Impaired insulin/IGF-1 signaling (IIS) and caloric restriction (CR) prolong
      lifespan in the nematode C. elegans. However, a cross comparison of these
      longevity pathways using a multi-omics integration approach is lacking. In this
      study, we aimed to identify key pathways and metabolite fingerprints of longevity
      that are shared between IIS and CR worm models using multi-omics integration. We
      generated transcriptomics and metabolomics data from long-lived worm strains,
      i.e. daf-2 (impaired IIS) and eat-2 (CR model) and compared them with the wild
      type strain N2. Transcriptional profiling identified shared longevity signatures,
      such as an upregulation of lipid storage and defense responses, and
      downregulation of macromolecule synthesis and developmental processes.
      Metabolomics profiling identified an increase in the levels of glycerol-3P,
      adenine, xanthine, and AMP, and a decrease in the levels of the amino acid pool,
      as well as the C18:0, C17:1, C19:1, C20:0 and C22:0 fatty acids. After we
      integrated transcriptomics and metabolomics data based on the annotations in
      KEGG, our results highlighted increased amino acid metabolism and an upregulation
      of purine metabolism as a commonality between the two long-lived mutants.
      Overall, our findings point towards the existence of shared metabolic pathways
      that are likely important for lifespan extension and provide novel insights into
      potential regulators and metabolic fingerprints for longevity.

PMID- 30300668
TI  - Hepatic signalling disruption by pollutant Polychlorinated biphenyls in
      steatohepatitis.
AB  - BACKGROUND: Polychlorinated biphenyl-mediated steatohepatitis has been shown to
      be due in part to inhibition of epidermal growth factor receptor (EGFR)
      signalling. EGFR signalling regulates many facets of hepatocyte function, but it
      is unclear which other kinases and pathways are involved in the development of
      toxicant-associated steatohepatitis (TASH). METHODS: Comparative hepatic
      phosphoproteomic analysis was used to identify which kinases were affected by
      either PCB exposure (Aroclor 1260 mixture), high fat diet (HFD), or their
      interaction in a chronic exposure model of TASH. Cellular assays and western blot
      analysis were used to validate the phosphoproteomic findings. RESULTS: 1760
      unique phosphorylated peptides were identified and of those 588 were
      significantly different. PCB exposure and dietary interaction promoted a near 25%
      reduction of hepatic phospho-peptides. Leptin and insulin signalling were
      pathways highly affected by PCB exposure and liver necrosis was a pathologic
      ontology over represented due to interaction between PCBs and a HFD. Casein
      kinase 2 (CK2), Extracellular regulated kinase (ERK), Protein kinase B (AKT), and
      Cyclin dependent kinase (CDK) activity were demonstrated to be downregulated
      after PCB exposure and this downregulation was exacerbated with a HFD. PCB
      exposure led to a loss of hepatic CK2 subunit expression limiting CK2 kinase
      activity and negatively regulating caspase-3 (CASP3). PCBs promoted secondary
      necrosis in vitro validating the latter observation. The loss of hepatic
      phosphoprotein signalling appeared to be due to decreased signal transduction
      rather than phosphatase upregulation. CONCLUSIONS: PCBs are signal disrupting
      chemicals that promote secondary necrosis through affecting a myriad of liver
      processes including metabolism and cellular maintenance. PCB exposure,
      particularly with interaction with a HFD greatly down-regulates the hepatic
      kinome. More data are needed on signalling disruption and its impact on liver
      health.

PMID- 30300669
TI  - Lifestyle segmentation and political ideology: Toward understanding beliefs and
      behavior about local food.
AB  - This research sought to better understand local food consumers and take steps to
      begin to identify how targeted messages could engage different groups. In order
      to accomplish these aims, data was collected through a survey mailed to a random
      sample of Wisconsin households with a final sample size of 577. These consumers
      were then segmented based on variables related to the food related lifestyle
      (FRL) and political ideology. Political ideology was included as it influences
      the media to which individuals pay attention, and how they interpret messages.
      Identified groups were further profiled with variables related to local food
      purchasing, frequency of shopping at farmers' markets and natural food stores,
      willingness to pay a premium for local food, perceptions related to local food,
      communication habits, and demographics. Five segments were identified, with three
      standing out as likely consumers of local produce. The liberal, "Adventurous"
      consumers showed a strong interest in local food, perceiving local food to be
      superior for its environmental benefits, among other reasons. The "Traditional"
      and "Rational" groups were not interested in local food for environmental
      reasons, and may find such messages unappealing. In order to engage these other
      groups, messages should address the high quality of local food, how it can be
      incorporated into traditional recipes (for the "Traditional" group), and ways to
      make local food affordable and convenient to buy (for the "Rational" group).

PMID- 30300670
TI  - The effects of reward and loss anticipation on attentional bias for reward
      related stimuli.
AB  - Attentional biases for reward-related (e.g., food, alcohol) cues are moderated by
      the expectation of imminent reward availability, but the psychological mechanisms
      that underlie this effect are unclear. We report two studies in which we
      investigated if effects of reward gain anticipation are specific to the type of
      reward that is anticipated, and if anticipation of loss has comparable effects to
      anticipation of reward gain. We used an eye tracking task to investigate the
      effects of anticipation of gain (experiment 1) or loss (experiment 2) of alcohol
      and chocolate on attentional bias for alcohol and chocolate pictures using full
      crossover designs; the effects of uncertain outcomes were investigated in both
      experiments. Results indicated robust effects of anticipation of reward gain and
      uncertainty on attentional bias that were outcome-specific (experiment 1).
      However attentional bias was not influenced by loss anticipation (experiment 2).
      Our findings demonstrate that anticipation of reward gain increases attentional
      bias for the type of reward that is anticipated, but anticipation of loss does
      not influence attentional bias.

PMID- 30300671
TI  - Vitamin E alleviates non-alcoholic fatty liver disease in
      phosphatidylethanolamine N-methyltransferase deficient mice.
AB  - Phosphatidylethanolamine N-methyltransferase (PEMT) converts
      phosphatidylethanolamine (PE) to phosphatidylcholine (PC), mainly in the liver.
      Pemt-/- mice are protected from high-fat diet (HFD)-induced obesity and insulin
      resistance, but develop severe non-alcoholic fatty liver disease (NAFLD) when fed
      a HFD, mostly due to impaired VLDL secretion. Oxidative stress is thought to be
      an essential factor in the progression from simple steatosis to steatohepatitis.
      Vitamin E is an antioxidant that has been clinically used to improve NAFLD
      pathology. Our aim was to determine whether supplementation of the diet with
      vitamin E could attenuate HFD-induced hepatic steatosis and its progression to
      NASH in Pemt-/- mice. Treatment with vitamin E (0.5 g/kg) for 3 weeks improved
      VLDL-TG secretion and normalized cholesterol metabolism, but failed to reduce
      hepatic TG content. Moreover, vitamin E treatment was able to reduce hepatic
      oxidative stress, inflammation and fibrosis. We also observed abnormal ceramide
      metabolism in Pemt-/- mice fed a HFD, with elevation of ceramides and other
      sphingolipids and higher expression of mRNAs for acid ceramidase (Asah1) and
      ceramide kinase (Cerk). Interestingly, vitamin E supplementation restored Asah1
      and Cerk mRNA and sphingolipid levels. Together this study shows that vitamin E
      treatment efficiently prevented the progression from simple steatosis to
      steatohepatitis in mice lacking PEMT.

PMID- 30300672
TI  - Genome-wide analysis reveals the effects of artificial selection on production
      and meat quality traits in Qinchuan cattle.
AB  - A new strain of Qinchuan cattle (QNS) has been obtained after more than forty
      years of selective breeding, and it shows good performance and production traits.
      To characterize the genetic changes that have resulted from breeding, we
      sequenced 10 QNS and 10 of the original breed Qinchuan cattle (QCC) for the first
      time, with average of 12.5-fold depth. A total of 31,242,284 and 29,612,517 SNPs
      were identified in the QCC and QNS genomes, 47.81% and 44.36% of which were found
      to be novel, respectively. Furthermore, population structure analysis revealed
      the selection that these cattle had experienced. Then, 332 and 571 potential
      selected genes were obtained, associated with enhanced immunity and
      acclimatization in QCC (CD5, SMARCA2, CATHL2, etc.) and production or meat
      quality traits in QNS (PLCD3, MB, PPARGC1A, etc.). These results revealed the
      efforts of selective breeding for Chinese Qinchuan cattle, and will be helpful
      for future cattle breeding.

PMID- 30300673
TI  - Affect dynamics of facial EMG during continuous emotional experiences.
AB  - Emotional experiences are complex, multi-component processes that unfold over
      time. Accordingly, it is crucial to understand the temporal dynamics of these
      constituent components. Here we studied the dynamics of one of the core emotional
      systems, i.e. facial muscle activity, during continuous emotional experiences,
      elicited by movies. We found that transient zygomatic fluctuations were narrowly
      tuned to a positive emotional experience. During a positive but not a negative
      movie, zygomatic response patterns were consistent across participants, tracked
      with subjective ratings and co-varied with emotional dynamics. Corrugator
      activity evidenced a broader affective profile and larger individual variability.
      It was coordinated with tonic changes in emotional negativity and inversely
      coupled with transient changes in positive affect. Taken together, our results
      confirmed previous findings on the affective profiles of facial responses and
      extended them to temporal dynamics. They further uncovered important differences
      in temporal response characteristics of zygomatic and corrugator measures.

PMID- 30300674
TI  - Conflict-related medial frontal theta as an endophenotype for alcohol use
      disorder.
AB  - Diminished cognitive control in alcohol use disorder (AUD) is thought to be
      mediated by prefrontal cortex circuitry dysregulation. Research testing the
      relationship between AUD and specific cognitive control psychophysiological
      correlates, such as medial frontal (MF) theta-band EEG power, is scarce, and the
      etiology of this relationship is largely unknown. The current report tested
      relationship between pathological alcohol use through young adulthood and reduced
      conflict-related theta at age 29 in a large prospective population-based twin
      sample. Greater lifetime AUD symptomatology was associated with reduced MF theta
      power during response conflict, but not alpha-band visual attention processing.
      Follow-up analyses using cotwin control analysis and biometric modeling suggested
      that genetic influences, and not the consequences of sustained AUD
      symptomatology, explained the theta-AUD association. Results provide strong
      evidence that AUD is genetically related to diminished conflict-related MF theta,
      and advance MF theta as a promising electrophysiological correlate of AUD-related
      dysfunctional frontal circuitry.

PMID- 30300675
TI  - Melatonin as an adjunct to therapeutic hypothermia in a piglet model of neonatal
      encephalopathy: A translational study.
AB  - Therapeutic hypothermia is only partially protective for neonatal encephalopathy;
      there is an urgent need to develop treatments that augment cooling. Our objective
      was to assess safety, efficacy and pharmacokinetics of 5 and 15 mg/kg/24 h
      melatonin (proprietary formulation) administered at 2 h and 26 h after hypoxia
      ischemia (HI) with cooling in a piglet model. Following moderate cerebral HI, 30
      piglets were eligible and randomized to: i) Hypothermia (33.5  degrees C, 2-26 h)
      and vehicle (HT + V;n = 13); b) HT and 5 mg/kg melatonin over 6 h at 2 h and 26 h
      after HI (HT + Mel-5;n = 4); c) HT and 15 mg/kg melatonin over 6 h at 2 h and 26
      h after HI (HT + Mel-15;n = 13). Intensive care was maintained for 48 h; brain
      MRS was acquired and cell death (TUNEL) evaluated at 48 h. Comparing HT + V with
      HT + Mel-5 and HT + Mel-15, there was no difference in blood pressure or
      inotropic support needed, brain Lactate/N Acetylaspartate at 24 h and 48 h was
      similar, ATP/phosphate pool was higher for HT + Mel-15 versus HT + V at 24 h (p =
      0.038) but not 48 h. A localized reduction in TUNEL positive cell death was
      observed in the sensorimotor cortex in the 15 mg/kg melatonin group (HT + Mel-15
      versus HT + V; p < 0.003) but not in the 5 mg/kg melatonin group (HT + Mel-5
      versus HT + V; p = 0.808). Putative therapeutic melatonin levels were reached 8 h
      after HI (104 increase from baseline; ~15-30 mg/l). Mean +/- SD peak plasma
      melatonin levels after the first infusion were 0.0014 +/- 0.0012 mg/l in the HT +
      V group, 3.97 +/- 1.53 mg/l in the HT + Mel-5 group and 16.8 +/- 8.3 mg/l in the
      HT + Mel-15 group. Protection was dose dependent; 15 mg/kg melatonin started 2 h
      after HI, given over 6 h, was well tolerated and augmented hypothermic protection
      in sensorimotor cortex. Earlier attainment of therapeutic plasma melatonin levels
      may optimize protection by targeting initial events of reperfusion injury. The
      time window for intervention with melatonin, as adjunct therapy with cooling, is
      likely to be narrow and should be considered in designing future clinical
      studies.

PMID- 30300676
TI  - Potentially missing data is considerably more frequent than definitely missing
      data: A methodological survey of 638 randomized controlled trials.
AB  - BACKGROUND: Missing data for the outcomes of participants in randomized
      controlled trials (RCTs) are a key element of risk of bias assessment. However,
      it is not always clear from RCT reports whether some categories of participants
      were followed-up or not (i.e., do or do not have missing data) nor how the RCT
      authors dealt with missing data in their analyses. OBJECTIVE: Our objectives were
      to describe how RCT authors: (1) report on different categories of participants
      that might have missing data; (2) handle these categories in the analysis; and
      (3) judge the risk of bias associated with missing data. METHODS: We surveyed all
      RCT reports included in 100 clinical intervention systematic reviews (SRs), half
      of which were Cochrane SRs. Eligible SRs reported a group-level meta-analysis of
      a patient-important dichotomous efficacy outcome, with a statistically
      significant effect estimate. Eleven reviewers, working in pairs, independently
      extracted data from the primary RCT reports included in the SRs. We pre-defined
      19 categories of participants that might have missing data. Then, we classified
      these participants as follows: 'explicitly followed-up', 'explicitly not followed
      up' (i.e., definitely missing data), or 'unclear follow-up status' (i.e.,
      potentially missing data). RESULTS: Of 638 eligible RCTs, 400 (63%) reported on
      at least one of the pre-defined categories of participants that might have
      missing data. The median percentage of participants who were explicitly not
      followed-up was 5.8% (IQR 2.2%-14.8%); it was 9.7% (4.1%-14.9%) for participants
      with unclear follow up status; and 11.7% (IQR 5.6%-23.7%) for participants who
      were explicitly not followed-up and with unclear follow up status. When authors
      explicitly reported not following-up participants, they most often conducted
      complete case analysis (54%). Most RCTs neither reported on missing data
      separately for different outcomes (99%) nor reported using a method for judging
      risk of bias associated with missing data (95%). CONCLUSION: 'Potentially missing
      data' is considerably more frequent than 'definitely missing data'. Adequate
      reporting of missing data will require development of explicit standards on which
      editors insist and to which RCT authors adhere.

PMID- 30300677
TI  - Electromechanics of polarized cell growth.
AB  - One of the most challenging questions in cell and developmental biology is how
      molecular signals are translated into mechanical forces that ultimately drive
      cell growth and motility. Despite an impressive body of literature demonstrating
      the importance of cytoskeletal and motor proteins as well as osmotic stresses for
      cell developmental mechanics, a host of dissenting evidence strongly suggests
      that these factors per se cannot explain growth mechanics even at the level of a
      single tip-growing cell. The present study addresses this issue by exploring
      fundamental interrelations between electrical and mechanical fields operating in
      cells. In the first instance, we employ a simplified but instructive model of a
      quiescent cell to demonstrate that even in a quasi-equilibrium state, ion
      transport processes are conditioned principally by mechanical tenets. Then we
      inquire into the electromechanical conjugacy in growing pollen tubes as
      biologically relevant and physically tractable developmental systems owing to
      their extensively characterized growth-associated ionic fluxes and strikingly
      polarized growth and morphology. A comprehensive analysis of the multifold stress
      pattern in the growing apices of pollen tubes suggests that tip-focused ionic
      fluxes passing through the polyelectrolyte-rich apical cytoplasm give rise to
      electrokinetic flows that actualize otherwise isotropic intracellular turgor into
      anisotropic stress field. The stress anisotropy can be then imparted from the
      apical cytoplasm to the abutting frontal cell wall to induce its local extension
      and directional cell growth. Converging lines of evidence explored in the
      concluding sections attest that tip-focused ionic fluxes and associated
      interfacial transport phenomena are not specific for pollen tubes but are also
      employed by a vast variety of algal, plant, fungal and animal cells, rendering
      their cytoplasmic stress fields essentially anisotropic and ultimately
      instrumental in cell shaping, growth and motility.

PMID- 30300678
TI  - Local and global dynamics in collective movements of embryonic cells.
AB  - Several important morphogenetic processes belong to the category of collective
      cell movements (CCM), by which we mean coordinated rearrangements of many
      neighboring cells. The causes of the dynamic order established during CCM are
      still unclear. We performed statistical studies of rates and angular orientations
      of cell rearrangements in two kinds of embryonic tissues, which we categorized as
      "committed" (in the sense of being capable of autonomous CCM) as opposed to
      "naive" tissues, which are those that require external forces in order to exhibit
      full scale CCM. In addition, we distinguished two types of cell rearrangements:
      first, those in which mutual cell-cell shifts characterizing the local dynamics
      (LD); and, second, those which moved in reference to common external coordinates
      (global dynamics, GD). We observed that in most cases LD rates deviated from
      normal distributions and do so by creating excesses of extensively converging and
      moderately diverging cells. In contrast, GD was characterized by nearly random
      behavior of slowly moving cells, combined with increased angular focusing of the
      fast cells trajectories as well as bimodal distribution of cell rates. When
      committed tissues were opposed by external mechanical forces, then they tended to
      preserve the inherent CCM patterns. On the other hand, the naive ones reacted by
      creating two orthogonal cells flows, one of these coinciding with the force
      direction. We consider CCM as a self-organizing process based on feedbacks
      between converging and diverging cell shifts, which is able to focus the
      trajectories imposed by external forces.

PMID- 30300679
TI  - PI3K pathway in prostate cancer: All resistant roads lead to PI3K.
AB  - The phosphoinositide 3-kinase (PI3K) pathway integrates multifarious
      environmental cues to regulate cell survival, growth, and metabolism.
      Hyperactivation of the PI3K pathway increases biological fitness by offering a
      high degree of adaptability to and resilience against diverse perturbations, thus
      conferring survival benefits on premalignant and transformed cells. In prostate
      cancer, the PI3K pathway is aberrantly activated by various genetic and
      epigenetic alterations and its hyperactivation is closely associated with a poor
      clinical outcome. In this review, we discuss the challenges encountered with
      clinically effective therapies targeting the PI3K pathway in prostate cancer,
      highlighting the clinical importance of combination therapies. In particular, we
      address how prostate cancer cells utilize the PI3K pathway for the development of
      resistance to a broad range of anticancer treatments. In addition, we describe
      the molecular mechanisms by which prostate cancer cells become resistant to PI3K
      pathway inhibitors. This review will be helpful in translating biological
      knowledge into therapeutic strategies for the treatment of prostate cancer and
      provide insight into overcoming therapeutic challenges associated with prostate
      cancer.

PMID- 30300680
TI  - Systemic L-buthionine-S-R-sulfoximine administration modulates glutathione
      homeostasis via NGF/TrkA and mTOR signaling in the cerebellum.
AB  - Glutathione (GSH) is an essential component of intracellular antioxidant systems
      that plays a primordial role in the protection of cells against oxidative stress,
      maintaining redox homeostasis and xenobiotic detoxification. GSH synthesis in the
      brain is limited by the availability of cysteine and glutamate. Cystine, the
      disulfide form of cysteine is transported into endothelial cells of the blood
      brain barrier (BBB) and astrocytes via the system xc-, which is composed of xCT
      and the heavy chain of 4F2 cell surface antigen (4F2hc). Cystine is reduced
      inside the cells and the L-type amino acid transporter 1 (LAT1) transports
      cysteine from the endothelial cells into the brain, cysteine is transported into
      the neurons through the excitatory amino acid transporter 3 (EAAT3), also known
      as excitatory amino acid carrier 1 (EAAC1). The mechanistic/mammalian target of
      rapamycin (mTOR) and neurotrophins can activate signaling pathways that modulate
      amino acid transporters for GSH synthesis. The present study found that systemic
      L-buthionine-S-R-sulfoximine (BSO) administration selectively altered GSH
      homeostasis and EAAT3 levels in the mice cerebellum. Intraperitoneal treatment of
      mice with 6 mmol/kg of BSO depleted GSH and GSSG in the liver at 2 h of
      treatment. The cerebellum, but not other brain regions, exhibited a redox
      response. The mTOR and the neuronal growth factor (NGF)/tropomyosin receptor
      kinase A (TrkA) signaling pathways were activated and lead to an increase in the
      protein levels of the EAAT3 transporter, which was linked to an increase in the
      GSH/GSSG ratio and GSH concentration in the cerebellum at 0.5 and 2 h,
      respectively. Therefore, the cerebellum responds to peripheral GSH depletion via
      activation of the mTOR and NGF/TrkA pathways, which increase the transport of
      cysteine for GSH synthesis.

PMID- 30300682
TI  - LGR5 acts as a target of miR-340-5p in the suppression of cell progression and
      drug resistance in breast cancer via Wnt/beta-catenin pathway.
AB  - Breast cancer is one of the most common malignant tumors among females. Recent
      studies demonstrated that microRNAs (miRNAs) played an important role in the
      regulation of tumor progression. In our present study, we firstly detected miR
      340-5p expression in breast cancer cell lines and found lower expression of miR
      340-5p in breast cancer cell lines (MCF-7, MDA-MB-231, BT-549, ZR-75-1) through
      qRT-PCR. Overexpressed miR-340-5p inhibited cell proliferation and drug
      resistance to docetaxel with enhanced cell apoptosis of breast cancer cells.
      Through bioinformatic prediction, we found that LGR5 was a potential target of
      miR-340-5p. LGR5 was highly expressed in breast cancer cells. Relative expression
      of LGR5 was negatively regulated by miR-340-5p. Knockdown of LGR5 also inhibited
      cell proliferation and drug resistance to docetaxel with enhanced cell apoptosis
      of breast cancer cells. Moreover, knockdown of LGR5 decreased the expression of
      beta-catenin, c-myc, Survivin. The activation of Wnt/beta-catenin pathway
      contracted the effects of LGR5 siRNA, indicating that LGR5 siRNA inhibited cell
      proliferation and drug resistance with induced apoptosis via suppressing Wnt/beta
      catenin signaling pathway in breast cancer. Taken together, our study
      demonstrated that overexpressed miR-340-5p inhibited cell proliferation and drug
      resistance with increased apoptosis of breast cancer cells through down
      regulating LGR5 expression via Wnt/beta-catenin pathway. The miR-340-5p/LGR5 axis
      may provide a new perspective for treatment for breast cancer.

PMID- 30300681
TI  - miR-323-3p regulates the steroidogenesis and cell apoptosis in polycystic ovary
      syndrome (PCOS) by targeting IGF-1.
AB  - Polycystic ovary syndrome (PCOS) is an endocrine and metabolic heterogeneous
      disorder. The incidence of which reaches 5% to 10% among reproductive-age women.
      Abnormal folliculogenesis is considered to be a common characteristic of PCOS,
      but the cause of this disorder and its pathogenesis still remain uncertain.
      Previous studies had proved that dysregulation of microRNAs is related to the
      pathogenesis of PCOS. In this study, we investigated the effect of miR-323-3p on
      the human cumulus cells (CCs). We also investigated the underlying mechanisms of
      miR-323-3p on human granulosa-like tumor cell line (KGN) or primary human CCs by
      stimulating with Dihydrotestosterone (DHT). Our findings suggested that the level
      of miR-323-3p in human CCs of women with PCOS was down-regulated, compared with
      that of the control group. Moreover, the inhibition of the level of miR-323-3p
      could up-regulate of the steroidogenesis and promote the apoptosis in KGN cells.
      In addition, our data confirmed that the Insulin-like growth factor 1 (IGF-1)
      gene was the direct target of miR-323-3p. Furthermore, the mimic of miR-323-3p
      inhibited the expression of IGF-1, which down-regulated the levels of AR, AMHR
      II, CYP19A, EGFR, and GATA-4. In conclusion, miR-323-3p targeting IGF-1 regulates
      the steroidogenesis and the activity of CCs, which plays an important role in the
      occurrence and development of PCOS. Our results have shown that miR-323-3p is a
      novel and promising molecular target for the improvement of the dysfunction of
      CCs in PCOS.

PMID- 30300683
TI  - Combined use of bFGF/EGF and all-trans-retinoic acid cooperatively promotes
      neuronal differentiation and neurite outgrowth in neural stem cells.
AB  - Neural stem cells (NSCs) as sources of new neurons in brain injuries or diseases
      are required to not only elicit neurons for neuronal repair, but also to enhance
      neurite outgrowth for neuronal network reestablishment. Various trophic or
      chemotropic factors have been shown to cooperatively improve NSC neurogenesis.
      However, effects of combined treatment of all-trans-retinoic acid (RA) with GF
      (Basic fibroblast growth factor and epidermal growth factor, bFGF/EGF) on
      neurogenesis of NSCs are poorly understood. To address this question, NSCs were
      isolated from the forebrains of embryonic mice, and treated with GF and RA either
      alone or in combination for differentiation in vitro. Neurons and astrocytes
      differentiated from NSCs were stained for MAP2 and GFAP separately by
      immunofluorescence. The results indicated that GF displayed superior efficacy in
      promoting neuronal differentiation, and RA showed better efficacy in advancing
      neurite outgrowth by increasing both neurite length and number. In addition,
      higher differentiation efficiency of neurons to astrocytes in RA or GF, or both
      acted at the early stage. However, more importantly, compared with RA alone, GF
      and RA in combination enhanced neuronal differentiation. Moreover, the combined
      use of GF and RA increased the length and number of neurites compared with GF, as
      well as the relative expression level of Smurf1. In addition, astrocytes induced
      by GF, RA, or both exhibited a radial glia-like morphology with long processes
      differing from serum effects, which might in part attribute to the total numbers
      of neurons. These findings for the first time unveil the roles of combined use of
      GF and RA on the neurogenesis of NSCs, suggesting that the use of this
      combination could be a comprehensive strategy for the functional repair of the
      nervous system through promoting neuronal differentiation, and advancing neurite
      outgrowth.

PMID- 30300684
TI  - Resting Heart Rate and Chronotropic Response to Exercise: Prognostic Implications
      in Heart Failure Across the Left Ventricular Ejection Fraction Spectrum.
AB  - BACKGROUND: We studied the relationship between resting heart rate (HR),
      chronotropic response to exercise, and clinical outcomes in patients with heart
      failure (HF) across the spectrum of left ventricle ejection fraction (LVEF).
      METHODS AND RESULTS: Resting HR and chronotropic index (CIx) were assessed in 718
      patients with HF (53 +/- 14 years of age, 66% male) referred for exercise
      testing. Associations with the composite outcome of left ventricular assist
      device implantation, transplantation, or death (151 events, 4.4 [range 3.0-5.8]
      years of follow-up) were assessed with the use of Cox models adjusted for age,
      sex, HF etiology, diabetes, LVEF, beta-blocker use, device therapy, estimated
      glomerular filtration rate, and peak oxygen uptake. Resting HR was 73 +/- 15
      beats/min, CIx was 0.60 +/- 0.26, LVEF was 34% +/- 15%, and 39% had an LVEF
      >=40%. Resting HR correlated poorly with CIx (r = 0.08; P = .04) and did not
      predict (P = .84) chronotropic incompetence (CIx <0.60). Both higher resting HR
      (per 5 beats/min increase: adjusted hazard ratio [HR] -1.05, 95% confidence
      interval [CI] 1.00-1.11) and CIx (per SD change: adjusted HR -0.77, 95% CI 0.62
      0.94) were independent prognostic markers. No heterogeneity of effect was noted
      based on LVEF (P >.05). CONCLUSION: Higher resting HR and lower CIx are both
      associated with more severe HF, but correlated poorly with each other. They
      provide independent and additive prognostic information in HF across the LVEF
      spectrum.

PMID- 30300685
TI  - The Crossroads of Frailty and Heart Failure: What More Can We Learn?

PMID- 30300686
TI  - Genetic hypercalcemia.
AB  - A genetic disorder should be suspected in patients with hypercalcemia, notably
      those who are young; have family members with hypercalcemia; or have had a tumor
      of the endocrine pancreas, thyroid, pituitary, adrenal gland, or jaw bone. All
      forms of hypercalcemia should be interpreted according to the serum level of
      parathyroid hormone (PTH). Genetic forms are thus classified as related or
      unrelated to a parathyroid gland disorder. When the PTH level is elevated or is
      not depressed despite the hypercalcemia, findings that suggest family history of
      hypercalcemia due to a genetic cause include syndromic manifestations in the
      patient or family members, parathyroid cancer (either suspected before surgery or
      confirmed during parathyroidectomy), multiple or recurrent parathyroid tumors, a
      family history of primary hyperparathyroidism, and the onset of primary
      hyperthyroidism before 50 years of age. In patients with moderate hypercalcemia,
      a normal PTH level, and relative hypocalciuria, the first hypothesis is a
      mutation in the calcium-sensing receptor gene, which is often difficult to
      distinguish from primary hyperparathyroidism, particularly when there is no known
      family history of hyperparathyroidism, as is often the case. A low PTH level
      suggests non-parathyroid hypercalcemia due to a genetic defect in patients with
      no evidence of other conditions associated with hypercalcemia and low PTH levels
      and in those whose calcitriol levels are elevated or normal (instead of depressed
      as expected when PTH is elevated). Patients with hypercalciuria but no evidence
      of conditions such as granulomatous diseases should be evaluated for increased
      vitamin D sensitivity due to a CYP 4A1 mutation. Other very rare causes include
      hypophosphatasia due to ALPL mutations, which is characterized by a low alkaline
      phosphatase level; and renal phosphate wasting due to an NPT2A mutation, in which
      serum phosphate levels are low. A thorough analysis of the clinical and
      laboratory data can point toward a genetic disorder in patients with
      hypercalcemia. The diagnosis is then confirmed by obtaining genetic tests
      tailored to the clinical and laboratory test abnormalities. The current
      development of diagnostic genetic testing is shedding new light on the
      phenotypes, thereby improving their management.

PMID- 30300687
TI  - Development of the human pancreas and its vasculature - An integrated review
      covering anatomical, embryological, histological, and molecular aspects.
AB  - OBJECTIVES: The aim of this study was to provide a comprehensive overview of the
      clinically relevant anatomical and histological aspects of the development of the
      human pancreas, with emphasis on the vascularization of the gland. METHODS: A
      comprehensive search on the relevant aspects of pancreatic biology was performed
      through the main electronic databases up to August 2017. Data from all relevant
      articles was gathered, analyzed and included in this narrative review. RESULTS:
      This review outlines the main topics on embryology, anatomy, histology, and
      molecular biology of the microcirculation of the human pancreas. The first part
      describes in detail the development of the pancreas synthesizing anatomical
      knowledge with findings of novel molecular studies. The second and third parts
      give information on the organization of arterial and venous pancreatic
      circulation. The final part summarizes the most important findings concerning
      pancreatic microcirculation. All parts taken together create a comprehensive and
      up-to-date description of the development and organization of the blood supply to
      the human pancreas. CONCLUSIONS: Detailed knowledge on the physiological
      development of the pancreas and anatomy of its blood supply play a key role in
      understanding the pathophysiology of various pancreatic disorders and is crucial
      for developing novel therapies for pancreatic disorders.

PMID- 30300688
TI  - Trial integration of combined ultrasound and laparoscopy tuition in an
      undergraduate anatomy class with volunteer participation - A pilot study.
AB  - Anatomy is a cornerstone of medical undergraduate curricula. Due to increasing
      changes in various medical fields, a lot of new subjects were introduced in
      undergraduate curricula, while the teaching areas of basic sciences, i.e.
      anatomy, were reduced. The introduction of advanced diagnostic and therapeutic
      devices, i.e. ultrasound and laparoscopy, with outstanding imaging quality will
      be increasingly introduced in basic sciences. In our project, we examined the
      effect integrating ultrasound and laparoscopy in an anatomy undergraduate course
      to illustrate the female pelvis. Anatomy students that completed their practicum
      and cadaver dissection course were enrolled in our project. They received a
      theoretical introduction followed by a practical course of ultrasound or
      laparoscopy in the department of obstetrics and gynaecology. Following the course
      the students had to answer two questionnaires that evaluated their satisfaction,
      subjective knowledge-gain, problems and content of the course. At the end, a
      closing briefing was done to discuss the clinical skills and the course. The
      answers of the questionnaire were summed up in a Likert scale. 25 students were
      enrolled in the project. 52% attended laparoscopy operations, while 48% attended
      ultrasound examinations. After analysing the questionnaires using Likert scales
      (1=strongly agree, 5=strongly disagree) a general satisfaction of 1.5, a
      subjective knowledge gain of 2.4 and a thrive to extend these clinical skill
      programs in gynaecology and other specialities in basic science of 1.5 and 1.2,
      respectively, was reported. There were no statistically significant differences
      in the Likert scores between both groups (p>0.05). The introduction of ultrasound
      and laparoscopy in undergraduate basic science teaching programs is a promising
      method and should be further evaluated, standardized and expanded.

PMID- 30300690
TI  - Comparative spermatozoal ultrastructure and molecular analysis in dromiid crabs
      and their phylogenetic implications for Dromiidae and Podotremata (Decapoda:
      Brachyura).
AB  - We described the spermatozoal ultrastructure and conducted a molecular analysis
      of Dromiidae Hypoconcha parasitica, Hypoconcha arcuata, Moreiradromia antillensis
      and Dromia erythropus. To elucidate the relationship between the different
      species of this brachyuran group, we also compared the spermatozoal morphologies
      and phylogenetic positioning among species of Dromiidae, Dromioidea and
      Podotremata. Specimens were collected from the northern coast of Sao Paulo,
      Brazil and were fixed and processed followed by transmission electron microscopy
      and molecular analysis routines. The Dromiidae spermatozoa studied are
      characterized by a discoidal acrosome, with three or four concentric zones, which
      are centrally separated by a bilaterally capitate perforatorial chamber, with a
      "mushroom"-shaped apex in the Hypoconchinae and a "T-shape" in Dromiinae. Above
      the perforatorial chamber, there is an apical protuberance, continuous with the
      subopercular region and the operculum, which forms a low, centrally perforated
      dome. Under differential interference contrast microscopy, the spermatozoa show 3
      to 4 radial arms. The spermatozoal characters in Hypoconchinae and Dromiinae do
      not separate these subfamilies from the Dromiidae and Dromioidea. Ultrastructural
      differentiation was only found between representative Dromioidea and other
      Podotremata. Thus, the spermiotaxonomy of these Hypoconcha, Moreiradromia and
      Dromia species corroborated previous morphological and molecular studies,
      supporting the monophyly of Dromiidae and Dynomenidae in relation to Homolidae
      and Latreilliidae.

PMID- 30300689
TI  - The Needs and Benefits of Continuous Model Updates on the Accuracy of RT-induced
      Toxicity Prediction Models within a Learning Health System.
AB  - BACKGROUND: and Purpose: Clinical data collection and development of outcome
      prediction models by machine learning can form the foundation for a learning
      health system offering precision radiotherapy. However, changes in clinical
      practice over time can affect the measures and outcomes of patients and hence the
      collected data. We hypothesize that regular prediction model updates along with
      continuous prospective data collection is important to prevent the degradation of
      a model's predication accuracy. MATERIAL AND METHODS: Clinical and dosimetric
      data from head and neck patients receiving intensity-modulated radiation therapy
      from 2008 to 2015 were prospectively collected as a routine clinical workflow and
      anonymized for the analysis. Prediction models for grade>=2 xerostomia at 3 to 6
      month follow-up were developed by bivariate logistic regression using DVH of
      parotid and submandibular glands. A baseline prediction model was developed with
      training dataset from 2008 to 2009. The selected predictor variables and
      coefficients were updated by four different model updating methods: (A) The
      prediction model was updated by using only recent two-year data and applied to
      patients in the following test year. (B) The model was updated by increasing the
      training dataset yearly. (C) The model was updated by increasing the training
      dataset on condition that the area under the curve (AUC) of the recent test year
      was less than 0.6. (D) The model was not updated. The AUC of the test dataset was
      compared among the four model updating methods. RESULTS: Dose to parotid and
      submandibular glands and grade of xerostomia showed decreasing trends over the
      years (2008-2015, 297 patients, p<0.001). The AUC of predicting grade>=2
      xerostomia for the initial training dataset (2008-2009, 41 patients) was 0.6196.
      The AUC for the test dataset (2010-2015, 256 patients) decreased to 0.5284 when
      the initial model was not updated (D). However, the AUC was significantly
      improved by model updates (A: 0.6164, B: 0.6084, p<0.05). When the model was
      conditionally updated, the AUC was 0.6072 (C). CONCLUSIONS: Our preliminary
      results demonstrate that updating prediction models with prospective data
      collection is effective for maintaining the performance of xerostomia prediction.
      This suggests that a machine learning framework can handle the dynamic changes in
      a radiation oncology clinical practice and may be an important component for the
      construction of a learning health system.

PMID- 30300692
TI  - Viscoelasticity of multicellular systems: From subcellular to supracellular
      levels.

PMID- 30300693
TI  - Need for preterm birth risk assessment in every pregnancy at any gestational age.

PMID- 30300691
TI  - Deformable liposomes for skin therapy with human epidermal growth factor: The
      effect of liposomal surface charge.
AB  - The topical administration of exogenous human epidermal growth factor (hEGF) is a
      promising approach for improved chronic wound therapy. To develop therapeutically
      superior hEGF formulation, we prepared hEGF-containing neutral (NDLs), cationic
      (CDLs) and anionic (ADLs) deformable liposomes (DLs), respectively, since it is
      expected that the liposomal surface charge can affect both the liposomal
      physicochemical properties, their skin penetration potential and therapeutic
      efficacy of liposome-associated drug. All prepared liposomes were of similar size
      (300-350 nm) with high hEGF load (~80% entrapment efficacy). Among the studied
      DLs, ADLs were found to be most promising for sustained release of hEGF, as
      assessed in vitro using the polyamide membrane. Ex vivo studies revealed that all
      DLs were excellent systems for skin therapy with hEGF and no penetration of hEGF
      through the full thickness human skin was detected. ADLs provided a depot
      exhibiting the highest hEGF retention onto the human skin surface. ADLs also
      revealed enhanced mitogenic activities in human fibroblasts compared to both NDLs
      and CDLs after 48 hrs treatment. Moreover, hEGF-containing ADLs significantly
      enhanced mitogenic activity in fibroblast as compared to activity of hEGF
      solution (positive control). Similar trends were observed in human keratinocytes
      after 24 hrs of treatment. We proved that the liposomal surface charge affects
      the therapeutic potential of hEGF-containing liposomes. hEGF-containing ADLs can
      be a promising nanosystem-based formulation for localized therapy of chronic
      wounds.

PMID- 30300694
TI  - Comparison of in vitro antibacterial activity of streptomycin-diclofenac loaded
      composite biomaterial dressings with commercial silver based antimicrobial wound
      dressings.
AB  - Infected chronic wounds heal slowly, exhibiting prolonged inflammation, biofilm
      formation, bacterial resistance, high exudate and ineffectiveness of systemic
      antimicrobials. Composite dressings (films and wafers) comprising
      polyox/carrageenan (POL-CAR) and polyox/sodium alginate (POL-SA), loaded with
      diclofenac (DLF) and streptomycin (STP) were formulated and tested for
      antibacterial activity against 2 * 105 CFU/mL of Escherichia coli, Pseudomonas
      aeruginosa and Staphylococcus aureus representing infected chronic wounds and
      compared with marketed silver dressings. Minimum inhibitory concentration (MIC)
      showed higher values for DLF than STP due to non-conventional antibacterial
      activity of DLF. The DLF and STP loaded dressings were highly effective against
      E. coli, P. aeruginosa and S. aureus. POL-SA dressings were more effective
      against the three types of bacteria compared to POL-CAR formulations, while the
      DLF and STP loaded dressings showed greater antibacterial activity than the
      silver-based dressings. The films, showed greater antibacterial efficacy than
      both wafers and silver dressings. STP and DLF can act synergistically not only to
      kill the bacteria but also prevent their resistance and biofilm formation
      compared to silver dressings, while reducing chronic inflammation associated with
      infection.

PMID- 30300695
TI  - Fucosterol exerts protection against amyloid beta-induced neurotoxicity, reduces
      intracellular levels of amyloid beta and enhances the mRNA expression of
      neuroglobin in amyloid beta-induced SH-SY5Y cells.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease that leads to progressive
      loss of neurons which often results in deterioration of memory and cognitive
      function. The development of AD is highly associated with the formation of senile
      plaques and neurofibrillary tangles. Amyloid beta (Abeta) induces neurotoxicity
      and contributes to the development of AD. Recent evidences also highlighted the
      importance of neuroglobin (Ngb) in ameliorating AD. This study assessed the
      ability of fucosterol, a phytosterol found in brown alga, in protecting SH-SY5Y
      cells against Abeta-induced neurotoxicity. Its effects on the mRNA levels of APP
      and Ngb as well as the intracellular Abeta levels were also determined in Abeta
      induced SH-SY5Y cells. SH-SY5Y cells were exposed to fucosterol prior to Abeta
      treatment. The effect on apoptosis was determined using Annexin V FITC staining
      and mRNA expression was studied using RT-PCR. Flow cytometry confirmed the
      protective effects of fucosterol on SH-SY5Y cells against Abeta-induced
      apoptosis. Pretreatment with fucosterol increased the Ngb mRNA levels but reduced
      the levels of APP mRNA and intracellular Abeta in Abeta-induced SH-SY5Y cells.
      These observations demonstrated the protective properties of fucosterol against
      Abeta-induced neurotoxicity in neuronal cells.

PMID- 30300696
TI  - Snakegourd root/Astragalus polysaccharide hydrogel preparation and application in
      3D printing.
AB  - Hydrogels have good water retention, biocompatibility and biodegradability, so
      they are well used in the medical industry. Here, we have active polysaccharide
      exacted from Chinese traditional medicine and carboxymethyl chitosan cross-linked
      to form hydrogel and characterized them by Scanning electron microscopy, FTIR
      analysis, swelling, degradation, release and cytotoxicity tests. We printed the
      composite hydrogel into patches with three different shapes by Hot-Melt extruded
      3D printer and studied the effects of different shapes on the release of drug.
      The results show, under acidic or alkaline conditions, the BSA cumulative release
      rate of the three hydrogel patches with different shape range from 49% to 89%.
      Therefore, there is a significant difference in the release between circular,
      cube and rectangular shape. Through the study, we found that the hydrogels we
      prepared have excellent potential for future applications in drug delivery
      system.

PMID- 30300697
TI  - Investigating the effect of chitosan on hydrophilicity and bioactivity of
      conductive electrospun composite scaffold for neural tissue engineering.
AB  - In this paper, nanofibers containing poly(epsilon-caprolactone) (PCL), chitosan
      and polypyrrole (PPy) were fabricated using electrospinning to combine advantages
      of electrospun nanofibers topography with versatile advantages of chitosan and
      PPy. Various compositions of the PCL/chitosan/PPy polymeric scaffolds were
      fabricated by electrospinning and were analyzed for their surface topography,
      hydrophilicity and bioactivity. The results illustrated that chitosan in the
      scaffold imposed significant advancement in the hydrophilicity of the scaffold as
      confirmed by a decrease in contact angle up to 66% (123 +/- 2.3 for PCL to 41.37
      +/- 3.51 for PCL/chitosan). The average diameter of the fibers was within the
      range of 30-180 nm, which influenced by the concentration of the chitosan as the
      increase up to 30% in chitosan content decreased fiber diameter from 124 nm to 36
      nm. In-vitro studies using PC12 cells revealed that the PCL/chitosan/PPy
      nanofibrous scaffold supports cell attachment, spreading and revealed significant
      increase in proliferation up to 356% in comparison to Pure PCL and neurite
      extension of PC12. The results indicated the PCL/chitosan/PPy nanofibrous
      scaffolds support the adhesion, spreading and proliferation of the PC12 cells.
      Therefore, this scaffold could serve as promising neural tissue substitutes.

PMID- 30300698
TI  - Osteogenic effectiveness of photo-immobilized bone morphogenetic protein-2 using
      different azidophenyl-natural polymer carriers in rat calvarial defect model.
AB  - The osteogenetic potential of photo-immobilized azdiophenyl (Az)-natural polymers
      as a carrier of bone morphogenetic protein-2 (BMP-2) was assessed in 56 rats
      randomized to four groups. The control group comprised implanted collagen sheet
      with BMP-2. In the three experimental groups, the implant comprised collagen
      sheet with photo-immobilized BMP-2 on Az-gelatin (Az-Gel), Az-O-carboxymethyl
      chitosan (Az-OMC), or Az-O-carboxymethyl low molecular chitosan (Az-LMC). Micro
      computed tomography analysis revealed more regenerated bone in Az-Gel at 8weeks.
      Immunohistochemical analysis at 4weeks revealed that the positively expressed
      cellular ratio in RUNX2-stained cells was significantly higher in Az-Gel and Az
      OMC groups. At 8weeks, only the Az-Gel group showed higher positively expressed
      cellular ratio compared with the control group. These results demonstrate the
      superior osteogenetic potential of photo-immobilized BMP-2 using Az-Gel carrier
      in a rat calvarial defect model compared with control group. Photo-immobilization
      of BMP-2 using Az-gelatin could be a more effective carrier system of BMP-2 than
      a chitosan-based carrier system.

PMID- 30300699
TI  - Advantages of short repetition time resting-state functional MRI enabled by
      simultaneous multi-slice imaging.
AB  - BACKGROUND: Recent advancements in simultaneous multi-slice (SMS) imaging
      techniques have enabled whole-brain resting-state fMRI (rs-fMRI) scanning at sub
      second temporal resolution, providing spectral ranges much wider than the
      typically used range of 0.01-0.1 Hz. However, the advantages of this accelerated
      acquisition for rs-fMRI have not been evaluated. NEW METHOD: In this study, we
      used SMS Echo Planar Imaging (EPI) to probe whole-brain functional connectivity
      with a short repetition time (TR = 350 ms) and compared it with standard EPI with
      a longer TR of 2000 ms. We determined the effect of scan length and investigated
      the temporal filtration strategies that optimize results based on metrics of
      signal-noise separation and test-retest reliability using both seed-based and
      independent component analysis (ICA). RESULTS: We found that use of either the
      entire frequency range of 0.01-1.4 Hz or the entire frequency range with the
      exclusion of typical cardiac and respiratory frequency values tended to provide
      the best functional connectivity maps. COMPARISON WITH EXISTING METHODS: We found
      that the SMS-acquired rs-fMRI scans had improved the signal-noise separation,
      while preserving the same level of test-retest reliability compared to
      conventional EPI, and enabled the detection of reliable functional connectivity
      networks with scan times as short as 3 min. CONCLUSIONS: Our findings suggest
      that whole-brain rs-fMRI studies may benefit from the increased temporal
      resolution enabled by the SMS-EPI acquisition, leading to drastic scan time
      reductions, which in turn should enable the more widespread use of rs-fMRI in
      clinical research protocols.

PMID- 30300700
TI  - Simulating human sleep spindle MEG and EEG from ion channel and circuit level
      dynamics.
AB  - BACKGROUND: Although they form a unitary phenomenon, the relationship between
      extracranial M/EEG and transmembrane ion flows is understood only as a general
      principle rather than as a well-articulated and quantified causal chain. METHOD:
      We present an integrated multiscale model, consisting of a neural simulation of
      thalamus and cortex during stage N2 sleep and a biophysical model projecting
      cortical current densities to M/EEG fields. Sleep spindles were generated through
      the interactions of local and distant network connections and intrinsic currents
      within thalamocortical circuits. 32,652 cortical neurons were mapped onto the
      cortical surface reconstructed from subjects' MRI, interconnected based on
      geodesic distances, and scaled-up to current dipole densities based on laminar
      recordings in humans. MRIs were used to generate a quasi-static electromagnetic
      model enabling simulated cortical activity to be projected to the M/EEG sensors.
      RESULTS: The simulated M/EEG spindles were similar in amplitude and topography to
      empirical examples in the same subjects. Simulated spindles with more core
      dominant activity were more MEG weighted. COMPARISON WITH EXISTING METHODS:
      Previous models lacked either spindle-generating thalamic neural dynamics or
      whole head biophysical modeling; the framework presented here is the first to
      simultaneously capture these disparate scales. CONCLUSIONS: This multiscale model
      provides a platform for the principled quantitative integration of existing
      information relevant to the generation of sleep spindles, and allows the
      implications of future findings to be explored. It provides a proof of principle
      for a methodological framework allowing large-scale integrative brain
      oscillations to be understood in terms of their underlying channels and synapses.

PMID- 30300701
TI  - Coding of "Home Cage" by PFC Neurons.
AB  - Contexts play critical roles in many important aspects of an animal's routine
      functions, such as the interpretation of incoming signals and retrieved memories.
      The roles played by prefrontal cortex (PFC) neurons in the coding of contexts
      have been largely studied in relation to aversive stimuli (such as foot shock in
      conditioned fear). Whether PFC neurons may code contexts that mice encounter in
      everyday life, such as their home cage, is poorly understood. Here, we report the
      identification of a subpopulation of ventral medial PFC (vmPFC) neurons which
      change their spike rates when mice enter or leave their home cages. Both increase
      (ON units) and decrease (OFF units) in spike rate were observed, with about 2/3
      of neurons showing decrease and 1/3 showing increase. These changes were evident
      whenever transitions occur from home cage to a different environment regardless
      of the novelty of the environments. In addition, changes in firing rate were not
      affected when mice entering a context where fear conditioning had taken place
      after contextual or auditory/cued fear conditioning. Furthermore, we found that
      the differential spike rates of ON and OFF units appear to allow mice to
      recognize that they are inside their home cages. Together, vmPFC neural spiking
      appears to enable the encoding of "home cage".

PMID- 30300702
TI  - Cross-modal Restoration of Juvenile-like Ocular Dominance Plasticity after
      Increasing GABAergic Inhibition.
AB  - In juvenile and young adult mice monocular deprivation (MD) shifts the ocular
      dominance (OD) of binocular neurons in the primary visual cortex (V1) away from
      the deprived eye. However, OD plasticity is completely absent in mice older than
      110 days, but can be reactivated by treatments which decrease GABA levels in V1.
      Typically, these OD shifts can be prevented by increasing GABAergic transmission
      with diazepam. We could recently demonstrate that both bilateral whisker and
      auditory deprivation (WD, AD), can also restore OD plasticity in mice older than
      110 days, since MD for 7 days in WD mice caused a potentiation of V1 input
      through the ipsilateral (open) eye, the characteristic feature of OD plasticity
      of "young adult" mice. Here we examined whether WD for 7 days also decreases GABA
      levels. For this, we performed post mortem HPLC analysis of V1 tissue. Indeed, we
      found that WD significantly decreased GABA levels in V1. Surprisingly, enhancing
      GABAergic inhibition by diazepam did not abolish OD shifts in WD mice, as
      revealed by repeated intrinsic signal imaging. On the contrary, this treatment
      led to a depression of V1 input through the previously closed contralateral eye,
      the characteristic signature of OD plasticity in juvenile mice during the
      critical period. Interestingly, the same result was obtained after AD. Taken
      together, these results suggest that cross-modally restored OD plasticity does
      not only depend on reduction of GABA levels in V1, but also requires other, so
      far unknown mechanisms.

PMID- 30300703
TI  - Inhibiting Succinate Dehydrogenase by Dimethyl Malonate Alleviates Brain Damage
      in a Rat Model of Cardiac Arrest.
AB  - Brain damage is a leading cause of death in patients with cardiac arrest (CA).
      The accumulation of succinate during ischemia by succinate dehydrogenase (SDH) is
      an important mechanism of ischemia-reperfusion injury. It was unclear whether
      inhibiting the oxidation of accumulated succinate could also mitigate brain
      damage after CA. In this study, rats were subjected to a 6 min of CA, and
      cardiopulmonary resuscitation (CPR) was performed with administration of normal
      saline or dimethyl malonate (DMM, a competitive inhibitor of SDH). After the
      return of spontaneous circulation, neurological function of the rats was assessed
      by a tape removal test for 3 days. The rats were then sacrificed, and their
      brains were used to assess neuronal apoptosis by terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) assay. Hippocampal tissues were used
      for Western blotting analysis and biochemical detection. In addition, hippocampal
      mitochondria during CA and CPR were isolated. The relative mitochondrial membrane
      potential (MMP) and cytochrome C in the cytosol were detected. Our results show
      that DMM promoted ROSC and neurological performance in rats after CA. The TUNEL
      assay showed that DMM reduced neuronal apoptosis. Western blotting analysis
      showed that DMM inhibited the activation of caspase-3 and enhanced the expression
      of HIF-1alpha. Moreover, DMM inhibited excessive hyperpolarization of MMP after
      CPR, and prevented the release of cytochrome C. Therefore, inhibiting SDH by DMM
      alleviated brain damage after CA, and the main mechanisms included inhibiting the
      excessive hyperpolarization of MMP, reducing the generation of mtROS and
      stabilizing the structure of HIF-1alpha.

PMID- 30300704
TI  - Local Injection of Endothelin-1 in the Early Neonatal Rat Brain Models Ischemic
      Damage Associated with Motor Impairment and Diffuse Loss in Brain Volume.
AB  - Cerebral palsy is an irreversible movement disorder resulting from cerebral
      damage sustained during prenatal or neonatal brain development. As survival
      outcomes for preterm injury improve, there is increasing need to model ischemic
      injury at earlier neonatal time-points to better understand the subsequent
      pathological consequences. Here we demonstrate a novel neonatal ischemic model
      using focal administration of the potent vasoconstrictor peptide, endothelin-1
      (ET-1), in newborn rats. The functional and histopathological outcomes compare
      favourably to those reported following the widely used hypoxic ischemia (HI)
      model. These include a robust motor deficit sustained into adulthood and
      recapitulation of hallmark features of preterm human brain injury, including
      atrophy of subcortical white matter and periventricular fiber bundles. Compared
      to procedures involving carotid artery manipulation and periods of hypoxia, the
      ET-1 ischemia model represents a rapid and technically simplified model more
      amenable to larger cohorts and with the potential to direct the locus of ischemic
      damage to specific brain areas.

PMID- 30300705
TI  - The Effects of Waveform and Current Direction on the Efficacy and Test-Retest
      Reliability of Transcranial Magnetic Stimulation.
AB  - The pulse waveform and current direction of transcranial magnetic stimulation
      (TMS) influence its interactions with the neural substrate; however, their role
      in the efficacy and reliability of single- and paired-pulse TMS measures is not
      fully understood. We investigated how pulse waveform and current direction affect
      the efficacy and test-retest reliability of navigated, single- and paired-pulse
      TMS measures. 23 healthy adults (aged 18-35 years) completed two identical TMS
      sessions, assessing resting motor threshold (RMT), motor-evoked potentials
      (MEPs), cortical silent period (cSP), short- and long-interval intra-cortical
      inhibition (SICI and LICI), and intracortical facilitation (ICF) using either
      monophasic posterior-anterior (monoPA; n = 9), monophasic anterior-posterior
      (monoAP; n = 7), or biphasic (biAP-PA; n = 7) pulses. Averages of each TMS
      measure were compared across the three groups and intraclass correlation
      coefficients were calculated to assess test-retest reliability. RMT was the
      lowest and cSP was the longest with biAP-PA pulses, whereas MEP latency was the
      shortest with monoPA pulses. SICI and LICI had the largest effect with monoPA
      pulses, whereas only monoAP and biAP-PA pulses resulted in significant ICF. MEP
      amplitude was more reliable with either monoPA or monoAP than with biAP-PA
      pulses. LICI was the most reliable with monoAP pulses, whereas ICF was the most
      reliable with biAP-PA pulses. Waveform/current direction influenced RMT, MEP
      latency, cSP, SICI, LICI, and ICF, as well as the reliability of MEP amplitude,
      LICI, and ICF. These results show the importance of considering TMS pulse
      parameters for optimizing the efficacy and reliability of TMS neurophysiologic
      measures.

PMID- 30300706
TI  - Polysorbate degradation in biotherapeutic formulations: Identification and
      discussion of current root causes.
AB  - Biotherapeutic protein formulations are often high concentration liquid protein
      solutions, which are required to be stable under pharmaceutically relevant
      storage conditions and presence of external stress. Non-ionic detergents like
      polysorbate have been the most commonly used detergent to maintain formulation
      stability. Recently, particle formation in polysorbate containing biotherapeutic
      formulations has arisen as a major quality concern and potential patient risk
      factor. In this review, we provide a general overview into (i) degradation of
      polysorbates, (ii) polysorbate analytics, (iii) particle formation induced by
      polysorbate degradation and root causes thereof, (iv) particle composition and
      (v) various influencing factors that might lead to particle formation.
      Consequently, we explore the role of polysorbate degradation in particle
      formation. Additionally, various degradation pathways and the current discussed
      root causes are reviewed.

PMID- 30300707
TI  - Antitumor effect of a liposome-encapsulated beta1,4-galactosyltransferase
      inhibitor.
AB  - Galactosyltransferases are a family of enzymes responsible for the synthesis of
      glycan chains which are involved in cell proliferation, adhesion and apoptosis. A
      recently synthesized galactosyltransferase inhibitor, 2-naphthyl 2-butanamido-2
      deoxy-1-thio-beta-D-glucopyranoside (612), has been found to selectively inhibit
      beta1,4-galactosyltransferase over beta1,3-galactosyltransferase and, therefore,
      has potential to suppress the synthesis of cancer associated epitopes. However,
      the application of this inhibitory activity in biological systems remains
      unknown. In this study, 612 was introduced into a cationic liposome (LP) delivery
      system, and the anti-proliferative effects of both free and the LP-incorporated
      612 (612-LP) were investigated in A549 lung cancer cells, which actively express
      anionic sialic acid moieties on the surfaces of cells. The anti-proliferative
      effects were evaluated via MTT assays. The results revealed that free 612 and
      empty LP impose neither anti-proliferative nor apoptotic effects on cancer cells
      at low doses, whereas the 612-LP system inhibited cancer cell growth at a
      concentration as low as 0.1 MUg/mL after 3 days of incubation, suggesting that
      this formulation enabled efficient delivery of 612 into cells and promoted the
      anti-proliferative activity of 612 against cancer cells. Therefore, this highly
      specific inhibitor 612 has the potential for development as an effective anti
      cancer agent and merits further investigation.

PMID- 30300708
TI  - Polysaccharide-based film loaded with vitamin C and propolis: A promising device
      to accelerate diabetic wound healing.
AB  - Wound healing can be a painful and time-consuming process in patients with
      diabetes mellitus. In light of this, the use of wound healing devices could help
      to accelerate this process. Here, cellulose-based films loaded with vitamin C
      (VitC) and/or propolis (Prop), two natural compounds with attractive properties
      were engineered. The starting materials and the cellulose-based films were
      characterized in detail. As assessed, vitamin C can be released from the Cel
      PVA/VitC and Cel-PVA/VitC/Prop films in a controlled manner. In vitro
      antibacterial activity studies showed a reduction of bacteria counts (Escherichia
      coli and Staphylococcus aureus) after Cel-PVA/VitC, Cel-PVA/Prop, and Cel
      PVA/VitC/Prop treatments. Moreover, we examined the antibacterial and wound
      healing properties of the cellulose-based films in a streptozotocin (STZ)-induced
      diabetic animal model. Diabetic mice exhibited impaired wound healing while the
      Cel-PVA/VitC/Prop treatment increased the wound closure. A marked reduction in
      bacterial counts present in the wound environment of diabetic mice was observed
      after Cel-PVA/VitC, Cel-PVA/Prop and Cel-PVA/VitC/Prop treatment. Histological
      analysis demonstrated that the non-treated diabetic mice group did not exhibit
      adequate wound healing while the treated group with Cel-PVA/VitC and Cel
      PVA/VitC/Prop films presented good cicatricial response. Furthermore, these novel
      eco-friendly films may represent a new therapeutic approach to accelerate
      diabetic wound healing.

PMID- 30300709
TI  - Analysis of pin milling of pharmaceutical materials.
AB  - Milling is an important process for tailoring the particle size distribution for
      enhanced dissolution, content uniformity, tableting, etc., specially for active
      pharmaceutical ingredients and excipient in pharmaceutical industries. Milling
      performance of particulate solids depends on the equipment operating conditions
      (geometry, process conditions and input energy etc.) as well as material
      properties (particle size, shape, and mechanical properties, such as Young's
      modulus, hardness and fracture toughness). In this work, a newly developed
      approach to assess the breakability of pharmaceutical materials using an
      aerodynamic dispersion method has been combined with the Discrete Element Method
      (DEM) to simulate the dynamic behaviour of a number of pharmaceutical materials
      in a pin mill. A sensitivity analysis is carried out addressing the effect of the
      milling conditions (rotational speed of the mill and feed particle flow rate) and
      feed properties on the milled products in terms of the shift in the specific
      surface area of the milled particles. The outcome of the work is used as a method
      to predict the breakage of the particles for the milling conditions where
      chipping takes place.

PMID- 30300710
TI  - Two siblings with a novel nonsense variant provide further delineation of the
      spectrum of recessive KLHL7 diseases.
AB  - Mutations in Kelch-like family member 7 (KLHL7) have recently been described as a
      cause of a constellation of clinical findings with descriptions of both a
      Crisponi syndrome (CS)/cold-induced sweating syndrome type 1 (CISS1)-like, as
      well as a Bohring-Opitz syndrome (BOS)-like presentation. Here we report two
      siblings of Guatelmalan descent with a novel homozygous nonsense mutation
      (p.Arg326*) in KLHL7. These children have multiple dysmorphic features and
      developmental delay. Interestingly, their clinical traits inconsistently overlap
      both the CS/CISS1-like and BOS-like phenotypes, and the siblings also have subtle
      differences from each other, suggesting that clinicians need to be aware of the
      degree of variability in the presentations of these patients. Still, there is
      enough in common between patients with recessive KLHL7 mutations to define a
      novel multisystem disease that features various neurodevelopmental,
      musculoskeletal, dysmorphic, and other unique components. This report adds to the
      clinical features and disease-associated variants of the newly-recognized
      spectrum of KLHL7 mutations, and offers a new description, PERCHING, for the
      resulting syndrome.

PMID- 30300711
TI  - Cartilaginous extracellular matrix derived from decellularized chondrocyte sheets
      for the reconstruction of osteochondral defects in rabbits.
AB  - Cartilaginous extracellular matrix (ECM) materials derived from decellularized
      native articular cartilage are widely used in cartilage regeneration. However, it
      is difficult for endogenous cells to migrate into ECM derived from native
      cartilage owing to its nonporous structure and dense nature. Moreover, current
      decellularization approaches frequently lead to architectural breakdown and
      potential loss of surface composition of ECM. To solve this problem, we aimed to
      establish a novel biological ECM scaffold from chondrocyte sheets for cartilage
      regeneration. We cultured chondrocytes harvested from the auricular cartilage of
      4-week-old New Zealand rabbits and enabled them to form cell sheets. These sheets
      were decellularized using sodium dodecyl sulfate (SDS) with three different
      concentrations, namely, 1%, 5%, and 10%, followed by 1% Triton X-100 and
      deoxyribonuclease enzyme solution. In vitro microstructural examination and
      mechanical tests demonstrated that 1% SDS not only removed chondrocytes
      completely but also maintained the native architecture and composition of ECM,
      thus avoiding the use of high-concentration SDS. Application of decellularized
      chondrocyte sheets for osteochondral defects in rabbits resulted in substantial
      host remodeling and variant regeneration of osteochondral tissues. One percent
      SDS-treated decellularized chondrocyte sheets contributed to the superior
      reconstruction of osteochondral defects as compared with 5% and 10% SDS groups,
      which includes vascularized subchondral bone, articular cartilage with adequate
      thickness, and integration with host tissues. Furthermore, ECM from 1% SDS
      significantly increased the migrating potential of bone marrow mesenchymal stem
      cells (BMSCs) in vitro. RT-PCR and western blot also revealed that ECM increased
      the expression of SOX-9 in BMSCs, whereas it decreased COL-X expression. In
      conclusion, our results suggested that the chondrocyte sheets decellularized with
      1% SDS preserved the integrity and bioactivity, which favored cell recruitment
      and enabled osteochondral regeneration in the knee joints of rabbits, thus
      offering a promising approach for articular cartilage reconstruction without cell
      transplantation. STATEMENT OF SIGNIFICANCE: Although biological extracellular
      matrix (ECM) derived from decellularized native cartilage has been widely used in
      cartilage regeneration, it is difficult for endogenous cells to migrate into ECM
      owing to its dense nature. Moreover, current decellularization approaches lead to
      architectural breakdown of ECM. This study established a novel biological ECM
      from decellularized chondrocyte sheets for cartilage regeneration. Our results
      suggested that cartilaginous ECM favored cell recruitment and enabled
      osteochondral regeneration in rabbits, thus offering a promising approach for
      articular cartilage reconstruction without cell transplantation. SDS 1%
      adequately decellularized the chondrocytes in cell sheets, whereas it maintained
      the native architecture and composition of ECM, thereby avoiding the use of high
      concentration SDS and providing a new way to acquire cartilaginous ECM.

PMID- 30300712
TI  - Ageing, the autonomic nervous system and arrhythmia: From brain to heart.
AB  - An ageing myocardium possesses significant electrophysiological alterations that
      predisposes the elderly patient to arrhythmic risk. Whilst these alterations are
      intrinsic to the cardiac myocytes, they are modulated by the cardiac autonomic
      nervous system (ANS) and consequently, ageing of the cardiac ANS is fundamental
      to the development of arrhythmias. A systems-based approach that incorporates the
      influence of the cardiac ANS could lead to better mechanistic understanding of
      how arrhythmogenic triggers and substrates interact spatially and temporally to
      produce sustained arrhythmia and why its incidence increases with age. Despite
      the existence of physiological oscillations of ANS activity on the heart,
      pathological oscillations can lead to defective activation and recovery
      properties of the myocardium. Such changes can be attributable to the decrease in
      functionality and structural alterations to ANS specific receptors in the
      myocardium with age. These altered ANS adaptive responses can occur either as a
      normal ageing process or accelerated in the presence of specific cardiac
      pathologies, such as genetic mutations or neurodegenerative conditions. Targeted
      intervention that seek to manipulate the ageing ANS influence on the myocardium
      may prove to be an efficacious approach for the management of arrhythmia in the
      ageing population.

PMID- 30300714
TI  - Role of 18F-fluoro-ethyl-tyrosine Positron Emission Tomography in Investigation
      and Management of Suspected Gliomas.
AB  - BACKGROUND: This study aims to investigate the utility of 18F-fluoro-ethyl
      tyrosine (18F-FET) positron emission tomography in surgical decision making in
      suspected glioma. METHODS: A retrospective review of patients undergoing 18F-FET
      positron emission tomography was performed. Previously published thresholds for
      maximum tumor background ratios (TBRs) were used for quantitative analysis. Forty
      seven patients were included in the study, of whom 15 had confirmed glioma and 7
      had a confirmed alternative diagnosis. RESULTS: 18F-FET showed significantly
      higher uptake in high-grade glioma than in nonglioma. CONCLUSIONS: Lesions with
      TBRmax >2.5 should be considered suspicious for glioma and biopsy considered.
      Threshold TBRmax >3.0 is useful for differentiating high-grade glioma from low
      grade glioma. This may be a particularly useful tool for directing management in
      eloquent areas, such as brainstem glioma.

PMID- 30300715
TI  - Workforce Analysis of Spine Surgeons Involved with Neurological and Orthopedic
      Surgery Residency Training.
AB  - OBJECTIVE: Spinal surgery is taught and practiced within 2 different surgical
      disciplines: neurological surgery and orthopedic surgery. We have provided a
      unified analysis of spine-focused faculty at U.S. residency programs. METHODS: A
      total of 278 Accreditation Council for Graduate Medical Education training
      programs were assessed to identify 923 full-time faculty members with a spinal
      surgery designation, defined by spine fellowship training or surgeon case volume
      >75% spine surgeries. Faculty were assessed with respect to parent discipline,
      years of fellowship training, academic rank, gender, and academic productivity (h
      index). RESULTS: The spine-teaching workforce contains 55% orthopedic surgeons
      and 45% neurosurgeons with wide gender asymmetry overall and at all faculty
      ranks. Of the female spine surgeons, those with neurosurgical training (64.44%)
      nearly doubled the number with orthopedic training (35.56%). Academic
      productivity increased with academic rank similarly for both genders and
      subspecialties. Orthopedic spine surgeons had a greater mean fellowship number
      compared with the neurological spine surgeons. Fellowship time of completion
      (intraresidency/infolded vs. postresidency) did not significantly affect the h
      indexes. Addition of fellowship conferred academic productivity benefit for
      orthopedic surgeons only. CONCLUSIONS: Neurological and orthopedic spine surgery
      showed similar patterns for the spread of faculty across academic ranks and
      trends in academic productivity. Marked gender disparity was seen in both
      neurosurgical and orthopedic surgery, with fewer female spine surgeons seen at
      every academic rank. Orthopedic spine surgeons had a greater mean fellowship
      number than did their neurosurgical counterparts, and a lack of fellowship
      correlated with lower academic productivity in orthopedic, but not neurological,
      spine surgery.

PMID- 30300713
TI  - Association networks in a matched case-control design - Co-occurrence patterns of
      preexisting chronic medical conditions in patients with major depression versus
      their matched controls.
AB  - OBJECTIVE: We present a method for comparing association networks in a matched
      case-control design, which provides a high-level comparison of co-occurrence
      patterns of features after adjusting for confounding factors. We demonstrate this
      approach by examining the differential distribution of chronic medical conditions
      in patients with major depressive disorder (MDD) compared to the distribution of
      these conditions in their matched controls. MATERIALS AND METHODS: Newly
      diagnosed MDD patients were matched to controls based on their demographic
      characteristics, socioeconomic status, place of residence, and healthcare service
      utilization in the Korean National Health Insurance Service's National Sample
      Cohort. Differences in the networks of chronic medical conditions in newly
      diagnosed MDD cases treated with antidepressants, and their matched controls,
      were prioritized with a permutation test accounting for the false discovery rate.
      Sensitivity analyses for the associations between prioritized pairs of chronic
      medical conditions and new MDD diagnosis were performed with regression modeling.
      RESULTS: By comparing the association networks of chronic medical conditions in
      newly diagnosed depression patients and their matched controls, five pairs of
      such conditions were prioritized among 105 possible pairs after controlling the
      false discovery rate at 5%. In sensitivity analyses using regression modeling,
      four out of the five prioritized pairs were statistically significant for the
      interaction terms. CONCLUSION: Association networks in a matched case-control
      design can provide a high-level comparison of comorbid features after adjusting
      for confounding factors, thereby supplementing traditional clinical study
      approaches. We demonstrate the differential co-occurrence pattern of chronic
      medical conditions in patients with MDD and prioritize the chronic conditions
      that have statistically significant interactions in regression models for
      depression.

PMID- 30300716
TI  - Micafungin is a novel anti-viral agent of chikungunya virus through multiple
      mechanisms.
AB  - The chikungunya virus (CHIKV) is a mosquito-borne virus that belongs to the genus
      Alphavirus, family Togaviridae. It is the cause of chikungunya fever in humans,
      which presents a serious global threat due to its high rate of contagion. The
      clinical symptoms of CHIKV include fever and persistent, severe arthritis.
      Micafungin has broad-spectrum fungicidal activity against Candida spp. is a
      promising echinocandin that was recently approved by the U.S. Food and Drug
      Administration (FDA) and has demonstrated activity against Candida and
      Aspergillus. Recent studies have demonstrated the antiviral activity of
      micafungin; however, the inhibitory effects against CHIKV have yet to be
      investigated. Our objectives in this study were to explore the antiviral effects
      of micafungin on CHIKV infection and to elucidate the potential molecular
      mechanisms of inhibition. We determined that micafungin has the ability to
      counter CHIKV-induced cytopathic effects. We further discovered that micafungin
      limits virus replication, release, cell-to-cell transmission, and also slightly
      affected virus stability during high doses treatment. The efficacy of micafungin
      was further confirmed against two clinical isolates of CHIKV and two
      alphaviruses: Sindbis virus (SINV) and Semliki Forest virus (SFV). Our findings
      suggest that micafungin has considerable potential as a novel inhibitor against
      the viral replication, and intracellular and extracellular transmission of CHIKV,
      and has a little effect on virus stability. Our findings also suggest that
      micafungin could have curative effects on other alphavirus infections.

PMID- 30300717
TI  - Elbasvir plus grazoprevir for patients with chronic hepatitis C genotype 1: A
      multicenter, real-world cohort study focusing on chronic kidney disease.
AB  - The real-world effectiveness and safety of all-oral direct-acting antivirals
      (DAAs) for chronic hepatitis C (HCV) infection and chronic kidney disease (CKD)
      have not been fully elucidated. This study assesses elbasvir (EBR) plus
      grazoprevir (GZR) for patients with HCV genotype 1 infection in the clinical
      setting, focusing on CKD stage 3-5D. This multicenter, real-world cohort study
      consisted of 282 Japanese patients who were treated with EBR (50 mg) plus GZR
      (100 mg) for a fixed 12-week duration. We evaluated the sustained viral response
      rate 12 weeks after the end of treatment (SVR12), longitudinal liver and renal
      parameters, and adverse effects according to the cirrhosis and CKD status. Of
      those enrolled, 89 (31.6%) were CKD stage 3-5 and 21 (7.4%) were CKD stage 5D
      (hemodialysis-dependent). The overall and CKD stage 3-5D SVR12 rates in the per
      protocol populations were 98.6% (272/276) and 98.1% (101/103). High SVR12 rates
      were observed in almost all groups, except for prior all-oral DAA failure with
      NS5A resistance-associated substitutions. There was no significant change during
      treatment or follow-up period in estimated glomerular filtration rate,
      irrespective of CKD status. In contrast, the serum complement level (C3 and C4)
      increased, with significance for C3. Serious adverse effects were very rare, both
      in the groups with normal eGFR and CKD, and discontinuation was required for only
      six (2.1%) patients. EBR plus GZR for HCV genotype 1 was highly effective with a
      low rate of adverse effects, regardless of CKD status. In addition, liver
      parameters and complement levels improved longitudinally.

PMID- 30300718
TI  - Early stages of drug crystallization from amorphous solid dispersion via fractal
      analysis based on chemical imaging.
AB  - Early stages of crystallization from amorphous solid dispersion (ASD) are
      typically not detected by means of standard methods like powder X-ray diffraction
      (XRPD). The aim of this study is therefore to evaluate if fractal analysis based
      on energy dispersive X-ray imaging can provide the means to identify early signs
      of physical instability. ASDs of the poorly water-soluble compound, felodipine
      (FEL) were prepared by solvent evaporation using different grades of HPMCAS, at
      50 wt% drug loading. Samples were stored at accelerated conditions of 40  degrees
      C. Scanning electron microscopy equipped with an energy-dispersive X-ray
      spectroscopy (SEM-EDS) was used for elemental mapping of tablet surfaces.
      Comparative data were generated with a standard XRPD and with more sensitive
      methods for detection of early instability, i.e. laser scanning confocal
      microscopy (LSM) and atomic force microscopy (AFM). The SEM-EDS identified
      changes of drug-rich domains that were confirmed by LSM and AFM. Early changes in
      drug clusters were also revealed by a multifractal analysis that indicated a
      beginning phase separation and drug crystallization. Therefore, the presented
      fractal cluster analysis based on chemical imaging bears much promise as a new
      method to detect early signs of physical instability in ASD, which is of great
      relevance for pharmaceutical development.

PMID- 30300719
TI  - Protein-polysaccharide nanohybrids: Hybridization techniques and drug delivery
      applications.
AB  - Complex nanosystems fabricated by hybridization of different types of materials
      such as lipids, proteins, or polysaccharides are usually superior to simple ones
      in terms of features and applications. Proteins and polysaccharides hold great
      potential for development of nanocarriers for drug delivery purposes based on
      their unique biocompatibility, biodegradability, ease of functionalization,
      improved biodistribution and minimal toxicity profiles. Protein-polysaccharide
      nanohybrids have gained a lot of attention in the past few years particularly for
      drug delivery applications. In this review, different hybridization techniques
      utilized in the fabrication of such nanohybrids including electrostatic
      complexation, Maillard conjugation, chemical coupling and electrospinning were
      thoroughly reviewed. Moreover, various formulation factors affecting the
      characteristics of the formed nanohybrids were discussed. We also reviewed in
      depth the outcomes of such hybridization ranging from stability enhancement, to
      toxicity reduction, improved biocompatibility, and drug release modulation. We
      also gave an insight on their limitations and what hinders their clinical
      translation and market introduction.

PMID- 30300720
TI  - Mechanistic modelling of intestinal drug absorption - The in vivo effects of
      nanoparticles, hydrodynamics, and colloidal structures.
AB  - Particle size reduction is a traditional approach to increase the intestinal
      absorption of active pharmaceutical ingredients with poor intestinal solubility,
      by increasing the particle dissolution rate. However, an increase in the
      dissolution rate cannot always fully explain the effects of nanoformulations, and
      a method of assessing the potential benefits of a nanoformulation in vivo would
      hence be of great value in drug development. A novel mathematical model of a
      nanoformulation, including interlinked descriptions of the hydrodynamics,
      particle dissolution and diffusion of particles and colloidal structures (CS),
      was developed to predict the combined in vivo effects of these mechanisms on drug
      absorption. The model successfully described previously reported in vivo
      observations of nanoformulated aprepitant in rats, at various drug concentrations
      and in the presence or absence of CS. The increase in absorption rate was
      explained as a direct consequence of the increased drug concentration at the
      membrane, caused by the contributing effects of the diffusion of both
      nanoparticles and CS into which the drug had partitioned. Further simulations
      supported the conclusion that the model can be applied during drug development to
      provide a priori assessments of the potential benefits of nanoformulations.

PMID- 30300721
TI  - DNA Demethylation by DNMT3A and DNMT3B in vitro and of Methylated Episomal DNA in
      Transiently Transfected Cells.
AB  - The DNA methylation program in vertebrates is an essential part of the epigenetic
      regulatory cascade of development, cell differentiation, and progression of
      diseases including cancer. While the DNA methyltransferases (DNMTs) are
      responsible for the in vivo conversion of cytosine (C) to methylated cytosine
      (5mC), demethylation of 5mC on cellular DNA could be accomplished by the combined
      action of the ten-eleven translocation (TET) enzymes and DNA repair.
      Surprisingly, the mammalian DNMTs also possess active DNA demethylation activity
      in vitro in a Ca2+- and redox conditions-dependent manner, although little is
      known about its molecular mechanisms and occurrence in a cellular context. In
      this study, we have used LC-MS/MS to track down the fate of the methyl group
      removed from 5mC on DNA by mouse DNMT3B in vitro and found that it becomes
      covalently linked to the DNA methylation catalytic cysteine of the enzyme. We
      also show that Ca2+ homeostasis-dependent but TET1/TET2/TET3/TDG-independent
      demethylation of methylated episomal DNA by mouse DNMT3A or DNMT3B can occur in
      transfected human HEK 293 and mouse embryonic stem (ES) cells. Based on these
      results, we present a tentative working model of Ca2+ and redox conditions
      dependent active DNA demethylation by DNMTs. Our study substantiates the
      potential roles of the vertebrate DNMTs as double-edged swords in DNA methylation
      demethylation during Ca2+-dependent physiological processes.

PMID- 30300722
TI  - Complementary feeding may pose a risk of simultaneous exposures to aflatoxin M1
      and deoxynivalenol in Indian infants and toddlers: Lessons from a mini-survey of
      food samples obtained from Kolkata, India.
AB  - A mini-survey of 29 different foods produced by 21 different Indian manufacturers
      was conducted for the presence of aflatoxins B1, B2, G1 and G2, aflatoxin M1 and
      deoxynivalenol. The products were purchased from local markets in Kolkata, India
      and commonly used in the complementary feeding of infants and toddlers in India.
      Using a previously established direct competitive enzyme-linked immunoassay for
      this analysis we show that 100% of the samples contained aflatoxin M1 at levels
      exceeding the recommended European Union levels of 25 ng kg-1 by more than an
      order of magnitude. Also, several (66%) of them contained detectable
      concentrations of deoxynivalenol with two samples (6.9%) exceeding European Union
      guidelines for baby food products (200 MUg kg-1) and 51.7% samples with DON
      levels that can lead to dietary intake higher than 1  MUg kg-1 recommended by the
      joint FAO/WHO expert committee on food additives. None of the samples contained
      aflatoxins B1, B2, G1 and G2. The results, therefore, suggest that complementary
      feeding can put Indian infants and toddlers at risk of simultaneous exposures to
      deoxynivalenol and aflatoxin M1 and warrant an urgent in-depth research to track,
      increase surveillance and reduce mycotoxin contamination of baby foods
      manufactured in India.

PMID- 30300723
TI  - RIFM fragrance ingredient safety assessment, 3a,7-methano-3ah
      cyclopentacycloocten-3-ol, decahydro-1,1,7-trimethyl-, formate, CAS Registry
      Number 58096-47-2.

PMID- 30300724
TI  - RIFM fragrance ingredient safety assessment, benzyl methyl ether, CAS Registry
      Number 538-86-3.

PMID- 30300725
TI  - RIFM fragrance ingredient safety assessment, 1,1-diethoxyheptane, CAS Registry
      Number 688-82-4.
AB  - The use of this material under current conditions is supported by existing
      information. 1,1-Diethoxyheptane was evaluated for genotoxicity, repeated dose
      toxicity, reproductive toxicity, local respiratory toxicity,
      phototoxicity/photoallergenicity, skin sensitization, and environmental safety.
      Data from the read-across analog octanal dimethyl acetal (CAS # 10022-28-3) show
      that 1,1-diethoxyheptane is not expected to be genotoxic. Based on the
      application of the non-reactive DST, 1,1-diethoxyheptane does not present a
      concern for skin sensitization. The repeated dose, developmental and
      reproductive, and local respiratory toxicity endpoints were completed using the
      TTC for a Cramer Class I material (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4
      mg/day, respectively). The phototoxicity/photoallergenicity endpoint was
      completed based on UV spectra. The environmental endpoints were evaluated; 1,1
      diethoxyheptane was found not to be PBT as per the IFRA Environmental Standards,
      and its risk quotients, based on its current volume of use in Europe and North
      America (i.e., PEC/PNEC), are <1.

PMID- 30300726
TI  - Maternal BDE-209 exposure during lactation perturbs steroidogenesis, germ cell
      kinetics and THRalpha1 expression in testes of prepubertal mice offspring.
AB  - Decabromodiphenyl ether (BDE-209), a congener of polybrominated diphenyl ethers
      (PBDEs), is used as flame retardant and affects thyroid homeostasis. Thyroid
      hormones (THs) play crucial role in Leydig cell differentiation and
      steroidogenesis during early life. Present study examined the effect of maternal
      BDE-209 exposure during lactation on testicular steroidogenesis and
      spermatogenesis in relation to thyroid hormone receptor alpha 1 (THRalpha1) and
      possible mechanism(s) of its action in prepubertal Parkes mice offspring.
      Lactating female Parkes mice were orally gavaged with 500, and 700 mg/kg body
      weight of BDE-209 in corn oil from postnatal day (PND) 1 to PND 28. Lactating
      mothers and male pups were sacrificed on PND 28. Maternal BDE-209 exposure
      markedly affected testicular histopathology, steroidogenesis and germ cell
      dynamics with downregulated expressions of various steroidogenic markers in mice
      offspring. Serum THs levels were markedly reduced in both pups and lactating
      mothers compared to controls. Expression of proliferating cell nuclear antigen
      and THRalpha1 also deceased in testes of BDE-209-exposed mice offspring. In
      silico analysis by molecular docking was performed successfully for steroidogenic
      facor-1 (SF-1) and THRalpha1 with BDE-209 and T3. Maternal BDE-209 exposure
      during lactation affects testicular steroidogenesis, spermatogenesis and
      expression of THRalpha1 in prepubertal mice offspring through downregulation of
      SF-1.

PMID- 30300727
TI  - RIFM fragrance ingredient safety assessment, beta-caryophyllene alcohol, CAS
      Registry Number 472-97-9.

PMID- 30300728
TI  - Development and validation of a ready to use cryo-EROD assay for the standardized
      screening of dioxins and dioxin-like compounds in foodstuffs.
AB  - Recent European regulations have indicated the need for new bioanalytical
      screening methods capable of monitoring dioxin and dioxin-like compounds in
      foodstuffs and environmental samples, cost-effectively and with a quicker
      turnaround. Cryo-cells of the hepatic H4IIE line preserved in 96-well plates were
      exposed to sample extracts prepared from various foodstuffs and analysed for
      their content of dioxins and dioxin-like compounds by means of the 7
      Ethoxyresorufin-O-Deethylase (EROD)-assay in two laboratories. Assay data were
      compared between both laboratories and results from instrumental analysis used as
      a confirmatory method. Additionally, cut-off values for the different studied
      matrices were derived. The current European regulation regarding methods of
      analysis for the control of foodstuffs was applied with the aim of determining
      the feasibility of the cryo-methodology. Results obtained in both laboratories
      were in congruence with the required validation parameters of the Commission
      Regulation (EU) No 2017/644. Cut-off values should be established matrix
      dependent to reduce the rate of false compliant results and to keep the rate of
      false non-compliant results under control. In summary, the ready-to-use cryo
      assay method for the bioanalytical screening of foodstuffs in control
      laboratories without cell-culture facilities has successfully proven to be
      accurate, far quicker and more cost effective than current methods.

PMID- 30300729
TI  - RIFM fragrance ingredient safety assessment, terpinyl isobutyrate, CAS Registry
      Number 7774-65-4.

PMID- 30300730
TI  - RIFM fragrance ingredient safety assessment, 3a,4,5,6,7,7a-hexahydro-4,7-methano
      1H-inden-5-yl pivalate, CAS Registry Number 68039-45-2.

PMID- 30300731
TI  - Reduced-Intensity Conditioning with Fludarabine, Melphalan, and Total Body
      Irradiation for Allogeneic Hematopoietic Cell Transplantation: The Effect of
      Increasing Melphalan Dose on Underlying Disease and Toxicity.
AB  - Disease relapse and toxicity are the shortcomings of reduced-intensity
      conditioning (RIC) for allogeneic hematopoietic cell transplantation (alloHCT).
      We hypothesized that adding total body irradiation (TBI) to and decreasing
      melphalan (Mel) from a base RIC regimen of fludarabine (Flu) and Mel would
      increase cytoreduction and improve disease control while decreasing toxicity. We
      performed a phase II trial of Flu 160 mg/m2, Mel 50 mg/m2, and TBI 400 cGy
      (FluMelTBI-50, n = 61), followed by a second phase II trial of Flu 160 mg/m2, Mel
      75 mg/m2, and TBI 400 cGy (FluMelTBI-75, n = 94) as RIC for alloHCT. Outcomes
      were compared with a contemporaneous cohort of 162 patients who received Flu 125
      mg/m2 and Mel 140 mg/m2. Eligibility criteria were equivalent for all 3 regimens.
      All patients were ineligible for myeloablative/intensive conditioning. The median
      (range) follow-up for all patients was 51 (15 to 103) months. Day 100 donor
      lymphoid chimerism and transplant-related mortality, neutrophil and platelet
      engraftment, acute and chronic graft versus host disease incidence, overall
      survival (OS), and progression-free survival (PFS) were equivalent between
      FluMel, FluMelTBI-50, and FluMelTBI-75. Stomatitis was decreased for FluMelTBI
      versus FluMel (P < .01). PFS for patients not in complete remission on alloHCT
      was improved for FluMelTBI-75 versus FluMel (P = .03). On multivariate analysis,
      OS (P = .05) and PFS (P = .05) were significantly improved for FluMelTBI-75
      versus FluMel. FluMelTBI-75 is better tolerated than FluMel, with improved
      survival and disease control.

PMID- 30300732
TI  - Interventions for common mental health problems among university and college
      students: A systematic review and meta-analysis of randomized controlled trials.
AB  - Common mental health problems (CMHPs), such as depression, anxiety disorder,
      obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD)
      are internalizing disorders with high comorbidity. University and college
      students are under many stressors and transitional events, and students fall
      within the age range when CMHPs are at their developmental peak. Compared to the
      expanded effort to explore and treat CMHPs, there has been no a meta-analysis
      that comprehensively reviewed the interventions for CMHPs and examined the
      effects of interventions for CMHPs in college students. The objective of this
      review is to conduct a systematic review and meta-analysis of randomized
      controlled trials (RCTs) examining interventions for CMHPs among university and
      college students and to estimate their post-intervention effect size (ES), as
      well as follow-up ES, for depression, anxiety disorder, OCD and PTSD separately.
      Meta-analytic procedures were conducted in accordance with PRISMA guidelines. We
      reviewed 7768 abstracts from which 331 full-text articles were reviewed and 51
      RCTs were included in the analysis. We found moderate effect sizes for both
      depression (Hedges' g = -0.60) and anxiety disorder (Hedges' g = -0.48). There
      was no evidence that existing interventions for OCD or PTSD were effective in
      this population. For interventions with high number of papers, we performed
      subgroup analysis and found that cognitive behavioral therapy (CBT) and
      mindfulness-based interventions were effective for both depression and
      generalized anxiety disorder (GAD), and attention/perception modification was
      effective for GAD; other interventions (i.e. art, exercise and peer support) had
      the highest ES for both depression and GAD among university and college students.

PMID- 30300734
TI  - Albuminuria and other renal damage biomarkers detect acute kidney injury soon
      after acute ingestion of oxalic acid and potassium permanganate.
AB  - BACKGROUND: Deliberate self-poisoning with a combination washing powder
      containing oxalic acid (H2C2O4) and potassium permanganate (KMnO4) is a
      significant medical problem in the Southern Province of Sri Lanka. Acute kidney
      injury (AKI) is a frequent consequence. Biomarkers for early diagnosis of
      nephrotoxicity could guide appropriate supportive therapies. METHODS: We
      investigated the performance of three serum biomarkers and nine urinary
      biomarkers in 85 patients in an ongoing multicenter prospective cohort study in
      Sri Lanka exploring AKI following poisoning. RESULTS: Sixty two (62/85, 73%)
      patients developed AKI (acute kidney injury network, AKIN, criteria). Early and
      rapid increases in serum creatinine (sCr) peaking on day 3 were observed in AKIN
      stage 2 and 3 patients. In these patients, serum cystatin C (sCysC) rose more
      gradually but also peaked on day 3. Biomarker concentrations (normalized to
      urinary creatinine) of urinary albumin (uAlbumin), clusterin (uClusterin), beta-2
      microglobulin (uB2M), osteopontin (uOPN), neutrophil gelatinase-associated
      lipocalin (uNGAL) and kidney injury molecule-1 (uKIM-1) in the AKIN2/3 group
      increased above the 95th centile concentration of the healthy population. Within
      8 h of ingestion, the normalized uAlbumin and sCysC predicted AKIN2/3 with
      respective area under receiver operating characteristic curve, AUC-ROC values, of
      0.94 (95% CI 0.86-1.00) and 0.85 (95% CI 0.76-0.95). CONCLUSIONS: Urinary albumin
      was the best performing AKI biomarker following ingestion of H2C2O4/KMnO4. This
      may reflect glomerular injury and/or proximal tubular injury. The urinary albumin
      concentrations observed in this study could generally be detected using albumin
      specific dipstick methods, easily available even in resource poor settings.

PMID- 30300735
TI  - Endothelial nitric oxide synthase enhancer AVE3085 reverses endothelial
      dysfunction induced by homocysteine in human internal mammary arteries.
AB  - Homocysteine (Hcy) is an independent risk factor for endothelial dysfunction in
      cardiovascular diseases. We hypothesized that the eNOS transcription enhancer
      AVE3085 may protect the endothelial function damaged by Hcy in the human internal
      mammary artery (IMA). Cumulative concentration-relaxation curves to acetylcholine
      (-10 to -4.5 log mol/L) or sodium nitroprusside were established in IMA from
      patients undergoing coronary artery surgery precontracted by U46619 (-8 log
      mol/L) in the absence/presence of Hcy (100 MUmol/L) with/without AVE3085 (30
      MUmol/L) in vitro in a myograph. RT-qPCR and ELISA were used to quantify the mRNA
      and protein levels of eNOS. Colorimetric assay method was used to detect the
      production of nitric oxide (NO). Maximal relaxation was significantly attenuated
      by Hcy in human IMA. Co-incubation with AVE3085 protected endothelium from the
      impairment by Hcy and increased the production of NO. Exposure to Hcy for 24 h
      downregulated eNOS protein expression (P < 0.05) whereas it upregulated the
      expression of eNOS at mRNA levels (P < 0.05). The presence of AVE3085 in addition
      to Hcy significantly increased the eNOS protein (P < 0.05) and slightly decreased
      the mRNA level. The study for the first time revealed that in the human blood
      vessels (IMA) the clinically-relevant high concentration of Hcy directly causes
      endothelial dysfunction by downregulating eNOS protein that may be reversed by
      AVE3085. These findings not only provide new direction for protecting endothelium
      during coronary artery bypass grafting and improving long-term patency of the
      grafts, but also provide evidence to the use of eNOS enhancer in the patients
      with endothelial dysfunction in various pathological conditions.

PMID- 30300733
TI  - Impact of in vitro heavy metal exposure on pancreatic beta-cell function.
AB  - Susceptibility to type-2 diabetes mellitus (DM) is determined, in part, by a
      variety of environmental factors, including exposure to metals. Heavy metals
      including inorganic arsenic (iAs), zinc (Zn), manganese (Mn), and cadmium (Cd)
      have been reported to affect glucose homeostasis or DM risk in population-based
      and/or laboratory studies. Previous evidence from our lab has shown that iAs can
      increase DM risk by impairing mitochondrial metabolism, one of the key steps in
      the regulation of glucose-stimulated insulin secretion (GSIS) in pancreatic beta
      cells. The goal of the current study was to compare the effects of iAs on GSIS
      and mitochondrial function in INS-1 832/13 beta-cells with those of Cd, Mn, and
      Zn, and to evaluate effects of binary mixtures of these metals. As expected, 24
      hour exposure to iAs (arsenite, >=1 MUM) significantly inhibited GSIS as did Cd
      (5 MUM) and Mn (12.5, 25, or 50 MUM). Zn had no effects on GSIS at concentrations
      up to 50 MUM. Mitochondrial function was assessed by measuring oxygen consumption
      rate (OCR) after glucose stimulation and during simulated mitochondrial stress.
      While both iAs and Mn impaired mitochondrial function (inhibiting OCR, maximal
      respiration, and/or spare respiratory capacity of mitochondria), no significant
      effects were found in cells exposed to Cd. Interestingly, no additive or
      synergistic effects on GSIS or OCR were observed in binary mixtures of iAs with
      either Mn or Cd. These data suggest that Mn, like iAs, may inhibit GSIS by
      impairing mitochondrial function, whereas Cd may target other mechanisms that
      regulate GSIS in beta-cells.

PMID- 30300736
TI  - An MBT domain containing anti-lipopolysaccharide factor (PtALF8) from Portunus
      trituberculatus is involved in immune response to bacterial challenge.
AB  - Anti-lipopolysaccharide factors are effective antimicrobial peptides that can
      bind and neutralize lipopolysaccharide (LPS). In the present study, a new
      sequence encoding for ALF (designated as PtALF8) was cloned by suppression
      subtractive hybridization method using ovary of swimming crab Portunus
      trituberculatus as material. The full-length cDNA of PtALF8 consisted of 531 bp
      with an ORF of 348 bp encoding a peptide of 115 amino acids containing a putative
      signal peptide of 19 amino acids. The mature PtALF8 had a predicted molecular
      weight (MW) of 11.28 kDa and theoretical isoelectricpoint (pI) of 5.11. The
      PtALF8 contains an MBT domain which was not found in the other 7 isoforms of ALF
      reported in P. trituberculatus. Unlike most ALFs expressed in hemocytes, PtALF8
      transcript was predominantly detected in hepatopancreas. After challenge with
      Vibrio alginolyticus, the temporal expression level of PtALF8 transcript in
      hemocytes reached the highest level at 3 h, then decreased to the lowest level at
      24 h, and started to increase at 48 h. The recombinant protein showed
      antimicrobial and bactericidal activity against several bacteria, such as Gram
      positive bacteria, Staphylococcus aureus, Micrococcus luteus and Gram-negative
      bacteria, V. alginolyticus, indicated that the PtALF8 isoform might play
      protective function against invading bacteria in P. trituberculatus.

PMID- 30300737
TI  - Two novel serine proteases from Scylla paramamosain involved in the synthesis of
      anti-lipopolysaccharide factors and activation of prophenoloxidase system.
AB  - Serine proteases (SPs) are important in various immune responses, including
      prophenoloxidase (proPO) activation, antimicrobial peptides (AMPs) synthesis, and
      hemolymph coagulation in invertebrates. In this study, SP3 and SP5 of mud crab
      (Scylla paramamosain) were studied. SP3 and SP5 were expressed in all examined
      tissues (mainly in hemocytes), and are associated with the immune responses of
      mud crab to Vibrio parahemolyticus and Staphylococcus aureus, as well as
      interacted with TRAF6, and are involved in the activation of anti
      lipopolysaccharide factors (ALFs) probably through the TLR/NF-kappaB pathway.
      Depletion of SP3 inhibited the expression of ALF1, ALF2, ALF3, and ALF6, while
      knockdown of SP5 significantly decreased ALF5, and ALF6. Furthermore, both SP5
      and TRAF6 regulated the PO activity in the hemolymph of mud crab. Overexpression
      assay showed that both SP3 and SP5 could enhance the promoter activities of ALFs
      in mud crab. Taken together, the results of this study indicate that SP3 and SP5
      might play important roles in the immune system of mud crab against pathogen
      invasion.

PMID- 30300738
TI  - Oral delivery of Bacillus subtilis spores expressing grass carp reovirus VP4
      protein produces protection against grass carp reovirus infection.
AB  - Grass carp (Ctenopharyngodon idellus) hemorrhagic disease (GCHD), caused by grass
      carp reovirus (GCRV), has given rise to an enormous loss in grass carp industry
      during the past years. Up to date, vaccination remained to be the most effective
      way to protect grass carp from GCHD. Oral vaccination is of major interest due to
      its advantages of noninvasive, time-saving, and easily-operated. The introduction
      of oral vaccination has profound impact on aquaculture industry because of its
      feasibility of extensive application for fish in various size and age. However,
      the main challenge in developing oral vaccine is that antigens are easily
      degraded and are easy to induce tolerance. Bacillus subtilis (B. subtilis) spores
      would be an ideal oral vaccine delivery system for their robust specialty, gene
      operability, safety and adjuvant property. VP4 protein is the major outer capsid
      protein encoded by GCRV segment 6 (S6), which plays an important role in viral
      invasion and replication. In this study, we used B. subtilis spores as the oral
      delivery system and successfully constructed the B. subtilis CotC-VP4 recombinant
      spores (CotC-VP4 spores) to evaluate its protective efficacy in grass carp. Grass
      carp orally immunized with CotC-VP4 spores showed a survival rate of 57% and the
      relative percent survival (RPS) of 47% after the viral challenge. Further, the
      specific IgM levels in serum and the specific IgZ levels in intestinal mucus were
      significantly higher in the CotC-VP4 group than those in the Naive group. The
      immune-related genes including three innate immune-related genes (IL-4/13A, IL
      4/13B, CSF1R), four adaptive immune-related genes (BAFF, CD4L, MHC-II, CD8),
      three inflammation-related genes (IL-1beta, TNF-alpha, TGF-beta) and interferon
      type I (IFN-I) related signaling pathway genes were significantly up-regulated in
      the CotC-VP4 group. The study demonstrated that the CotC-VP4 spores produced
      protection in grass carp against GCRV infection, and triggered both innate and
      adaptive immunity post oral immunization. This work highlighted that Bacillus
      subtilis spores were powerful platforms for oral vaccine delivery, and the
      combination of Bacillus subtilis spores with GCRV VP4 protein was a promising
      oral vaccine.

PMID- 30300739
TI  - Responses of Mytilus galloprovincialis to challenge with the emerging marine
      pathogen Vibrio coralliilyticus.
AB  - Vibrio coralliilyticus has emerged as a coral pathogen of concern throughout the
      Indo-Pacific reef. The interest towards understanding its ecology and pathogenic
      potential has increased since V. coralliilyticus was shown to be strongly
      virulent also for other species; in particular, it represents a serious threat
      for bivalve aquaculture, being one of the most important emerging pathogen
      responsible for oyster larval mortalities worldwide. V. coralliilyticus has a
      tightly regulated temperature-dependent virulence and it has been related to mass
      mortalities events of benthic invertebrates also in the temperate northwestern
      Mediterranean Sea. However, no data are available on the effects of V.
      coralliilyticus in the mussel Mytilus galloprovincialis, the most abundant
      aquacultured species in this area. In this work, responses of M.
      galloprovincialis to challenge with V. coralliilyticus (ATCC BAA-450) were
      investigated. In vitro, short term responses of mussel hemocytes were evaluated
      in terms of lysosomal membrane stability, bactericidal activity, lysozyme
      release, ROS and NO production, and ultrastructural changes, evaluated by TEM. In
      vivo, hemolymph parameters were measured in mussels challenged with V.
      coralliilyticus at 24h p.i. Moreover, the effects of V. coralliilyticus on mussel
      early embryo development (at 48 hpf) were evaluated. The results show that both
      in vitro and in vivo, mussels were unable to activate immune response towards V.
      coralliilyticus, and that challenge mainly induced lysosomal stress in the
      hemocytes. Moreover, V. coralliilyticus showed a strong and concentration
      dependent embryotoxicity. Overall, the results indicate that, although M.
      galloprovincialis is considered a resistant species to vibrio infections, the
      emerging pathogen V. coralliilyticus can represent a potential threat to mussel
      aquaculture.

PMID- 30300740
TI  - Effects of glycinin and beta-conglycinin on growth performance and intestinal
      health in juvenile Chinese mitten crabs (Eriocheir sinensis).
AB  - This study investigates the effects of two soybean antigens (glycinin and beta
      conglycinin) as an antinutritional substance in the diet on the growth, digestive
      ability, intestinal health and microbiota of juvenile Chinese mitten crabs
      (Eriocheir sinensis). The isonitrogenous and isolipidic diets contained two
      soybean antigens at two levels each (70 and 140 g/kg beta-conglycinin, 80 and 160
      g/kg glycinin) and a control diet without beta-conglycinin or glycinin
      supplementation, and were used respectively to feed juvenile E. sinensis for
      seven weeks. Dietary inclusion of either glycinin or beta-conglycinin
      significantly reduced crab survival and weight gain. The crabs fed diets
      containing soybean antigens had higher malondialdehyde concentrations and lower
      catalase activities in the intestine than those in the control. The activities of
      trypsin and amylase in the intestine were suppressed by dietary beta-conglycinin
      and glycinin. Dietary glycinin or beta-conglycinin impaired the immunity and
      morphological structure of intestine, especially the peritrophic membrane. The
      mRNA expression of constitutive and inducible immune responsive genes
      (lipopolysaccharide-induced TNF-alpha factor and interleukin-2 enhancer-binding
      factor 2) increased while the mRNA expression of the main genes related to the
      structural integrity peritrophic membrane (peritrophin-like gene and peritrophic
      2) significantly decreased in the groups with soybean antigen addition. Soybean
      antigen could also change the intestinal microbial community. The abundance of
      pathogenic bacteria (Ochrobactrum, Burkholderia and Pseudomonas) increased
      significantly in both soybean antigen groups. Although pathogenic bacteria Vibrio
      were up-regulated in the glycinin group, the abundance of Dysgonomonas that
      degraded lignocellulose and ameliorated the gut environment decreased in the
      glycinin group. This study indicates that existence of soybean antigens (glycinin
      or beta-conglycinin) could induce gut inflammation, reshape the community of gut
      microbiota, and cause digestive dysfunction, ultimately leading to impaired
      growth in crabs.

PMID- 30300741
TI  - Identification and characterization of a carboxypeptidase N1 from red lip mullet
      (Liza haematocheila); revealing its immune relevance.
AB  - Complement system orchestrates the innate and adaptive immunity via the
      activation, recruitment, and regulation of immune molecules to destroy pathogens.
      However, regulation of the complement is essential to avoid injuries to the
      autologous tissues. The present study unveils the characteristic features of an
      important complement component, anaphylatoxin inactivator from red lip mullet at
      its molecular and functional level. Mullet carboxypeptidase N1 (MuCPN1) cDNA
      sequence possessed an open reading frame of 1347 bp, which encoded a protein of
      449 amino acids with a predicted molecular weight of 51 kDa. In silico analysis
      discovered two domains of PM14-Zn carboxypeptidase and a C-terminal domain of M14
      N/E carboxypeptidase, two zinc-binding signature motifs, and an N-glycosylation
      site in the MuCPN1 sequence. Homology analysis revealed that most of the residues
      in the sequence are conserved among the other selected homologs. Phylogeny
      analysis showed that MuCPN1 closely cladded with the Maylandia zebra CPN1 and
      clustered together with the teleostean counterparts. A challenge experiment
      showed modulated expression of MuCPN1 upon polyinosinic:polycytidylic acid and
      Lactococcus garviae in head kidney, spleen, gill, and liver tissues. The highest
      upregulation of MuCPN1 was observed 24 h post infection against poly I:C in each
      tissue. Moreover, the highest relative expressions upon L. garviae challenge were
      observed at 24 h post infection in head kidney tissue and 48 h post infection in
      spleen, gill, and liver tissues. MuCPN1 transfected cells triggered a 2.2-fold
      increase of nitric oxide (NO) production upon LPS stimulation compared to the un
      transfected controls suggesting that MuCPN1 is an active protease which releases
      arginine from complement C3a, C4a, and C5a. These results have driven certain way
      towards enhancing the understanding of immune role of MuCPN1 in the complement
      defense mechanism of red lip mullet.

PMID- 30300742
TI  - IgM and IgD heavy chains of yellow catfish (Pelteobagrus fulvidraco): Molecular
      cloning, characterization and expression analysis in response to bacterial
      infection.
AB  - Three different immunoglobulin (Ig) isotypes, namely IgM, IgD, and IgT/IgZ have
      been described in most teleost, among which IgM and IgT are considered crucial in
      systematic and mucosal immunity, respectively. However, some teleost have no
      IgT/IgZ and it is unclear how other Ig isotypes interact to perform immune
      protective roles in both systematic and mucosal sites. In this study, the
      complete cDNA sequences of IgM and IgD heavy chains were cloned and analyzed from
      yellow catfish (Pelteobagrus fulvidraco). The full-length cDNA of Pf-IgM and Pf
      IgD heavy chains contained an open reading frame (ORF) of 1710 and 2991 bp
      encoding a predicted protein of 570 and 997 amino acids, respectively. Tissue
      specific expression analysis indicated that both IgM and IgD were highly
      expressed in kidney and spleen, and higher expression levels were found at zygote
      and 13th day post hatching during early development. Multiple sequence alignment
      and phylogenetic analysis showed IgM and IgD of yellow catfish are closely
      related to other fish of Siluriformes. Moreover, we also constructed the
      infection model of yellow catfish with bacteria (Flavobacterium columnare G4) for
      the first time to study the function of Pf-IgM and Pf-IgD heavy chain genes in
      immune response. Quantitative real-time PCR (qRT-PCR) showed that significantly
      up-regulated expression of Pf-IgM was not only detected in liver and spleen, but
      also in mucosal tissues including skin and intestine, while Pf-IgD was just
      significantly increased in liver and spleen, which might suggest the main immune
      protecting roles of IgM in mucosal tissues of yellow catfish.

PMID- 30300743
TI  - Quantitative mass spectrometry to identify protein markers for diagnosis of
      malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is a devastating malignancy with a prognosis
      of <12 months. Even with bans on the use of asbestos in most Western countries,
      the incidence is still increasing due to the long latency periods between
      exposure and development of the disease. Diagnosis is often delayed due to
      invasive biopsies and lack of distinguishable markers. Patients frequently
      present with pleural effusions months to years before a radiologically detectable
      mass appears. This study aimed to investigate the proteome of pleural effusions
      taken from patients with MPM, adenocarcinoma and benign conditions in an attempt
      to identify a biomarker for early diagnosis. We identified several proteins that
      may be possible targets and warrant further investigation. Due to the
      predominance of up regulated proteins involved in VEGF signalling in MPM, we
      analysed VEGFA levels in effusions and found a strong correlation between VEGFA
      levels and survival in MPM.

PMID- 30300744
TI  - The effect of a telephone-based self-management program led by nurses on self
      care behavior, biological index for cardiac function, and depression, in
      ambulatory heart failure patients.
AB  - PURPOSE: This study was conducted to examine the effects of a telephone-based
      self-management support program led by nurses on self-care behavior, biological
      index for cardiac function and depression. METHODS: This study is a quasi
      experiment in nonequivalent control group design. 36 heart failure patients were
      conducted in medical treatment at the hospital (18 heart failure patients in
      experimental group and 18 heart failure patients in control group). The
      experimental group (n=18) received the telephone-based self-management support
      program, which included a 30-minute face-to-face education session and 4
      telephone consultation and education sessions. The face-to-face education session
      was conducted at the first visit to the out-patient clinic. Thereafter, weekly
      telephone consultations and education sessions were performed for 4 weeks. Data
      were analyzed using descriptive statistics, Chi-square test, Fisher's exact test,
      independent t-test, paired t-test, repeated measures ANOVA using the SPSS/WIN
      21.0. RESULTS: The participants in the experimental group showed significantly
      increased self-care behavior scores (t=6.65, p<.001), decreased NT-proBNP level
      (U=-2.28, p=.022), improved LV EF values (t=2.24, p=.032), and decreased
      depression scores (t=-3.49, p=.001) compared to the control group. CONCLUSION:
      The findings indicate that the telephone-based self-management program is an
      effective intervention to improve self-management in heart failure patients.

PMID- 30300745
TI  - Age-related differences in the activation of the mentalizing- and reward-related
      brain regions during the learning of others' true trustworthiness.
AB  - Behavioral studies suggest that older adults may be less adept than younger
      adults at remembering information contradicting their first impressions about
      others' trustworthiness. To identify the neural bases associated with such age
      related differences, we measured the brain activity of older and younger
      participants using functional magnetic resonance imaging while they processed
      feedback on whether their initial trustworthiness impressions of stimulus
      persons, whose true trustworthiness had been predetermined, were right or wrong.
      Of special interest was the activation in mentalizing- (e.g., medial prefrontal
      cortex) and reward-related brain regions (e.g., striatum), which are known to be
      involved in impression formation and feedback learning, respectively. The
      reduction in the striatal responses to impression-contradicting versus impression
      confirming feedback was greater in older than in younger participants. The
      activation of some mentalizing-related regions (medial prefrontal cortex and
      precuneus) was lower in older than younger participants; however, it was not
      modulated by impression-feedback congruency. The results suggest that age-related
      differences in the striatum engagement may underlie older adults' inefficiency in
      learning impression-incongruent information about others' trustworthiness.

PMID- 30300746
TI  - Dehydration during egg production alters egg composition and yolk immune
      function.
AB  - Parent-offspring conflicts occur when resources are limited for allocation, and,
      historically, energy has been the primary currency of focus when examining these
      trade-offs. Water is a fundamental resource that has received far less
      consideration for parent-offspring conflicts. Previous research suggests that,
      when water is limited, reproductive females are compromised in favor of
      developing embryos. However, these studies limited their assessments to standard
      metrics such as clutch size and mass. We tested the hypothesis that the mother
      offspring conflict over limited water resources leads to finer scale
      morphological and physiological impacts on the eggs in Children's pythons
      (Antaresia childreni). We predicted that water deprivation during gravidity
      alters female investment into her eggs, impacting egg water content and shell
      development. Additionally, we predicted that the yolk in these dehydrated eggs
      would have enhanced immune performance metrics, as has been documented in
      dehydrated adults. We found that eggs from water-deprived females were dehydrated
      as indicated by reduced percent water and greater yolk osmolality compared to
      eggs from females that received ad libitum water. We also found that eggs from
      dehydrated mothers had thinner shells and higher water loss rates. The impacts
      were not entirely negative as dehydrated eggs had higher antimicrobial
      capabilities. Also, thinner and more permeability eggshells might allow for
      elevated rates of rehydration from nest substrate. Overall, by examining an array
      of egg traits, we demonstrated that dehydration of gravid females impacts the
      eggs, not just the females as previously reported. As a result, the mother
      offspring conflicts are indeed two-sided.

PMID- 30300747
TI  - Role of flow-sensitive microRNAs and long noncoding RNAs in vascular dysfunction
      and atherosclerosis.
AB  - Atherosclerosis is the primary underlying cause of myocardial infarction,
      ischemic stroke, and peripheral artery disease. The disease preferentially occurs
      in arterial regions exposed to disturbed blood flow, in part, by altering
      expression of flow-sensitive coding- and non-coding genes. In this review, we
      summarize the role of noncoding RNAs, [microRNAs (miRNAs) and long noncoding
      RNAs(lncRNAs)], as regulators of gene expression and outline their relationship
      to the pathogenesis of atherosclerosis. While miRNAs are small noncoding genes
      that post-transcriptionally regulate gene expression by targeting mRNA
      transcripts, the lncRNAs regulate gene expression by diverse mechanisms, which
      are still emerging and incompletely understood. We focused on multiple flow
      sensitive miRNAs such as, miR-10a, -19a, -23b, -17~92, -21, -663, -92a, -143/145,
      -101, -126, -712, -205, and -155 that play a critical role in endothelial
      function and atherosclerosis by targeting inflammation, cell cycle,
      proliferation, migration, apoptosis, and nitric oxide signaling. Flow-dependent
      regulation of lncRNAs is just emerging, and their role in vascular dysfunction
      and atherosclerosis is unknown. Here, we discuss the flow-sensitive lncRNA STEEL
      along with other lncRNAs studied in the context of vascular pathophysiology and
      atherosclerosis such as MALAT1, MIAT1, ANRIL, MYOSLID, MEG3, SENCR, SMILR,
      LISPR1, and H19. Also discussed is the use of these noncoding RNAs as potential
      biomarkers and therapeutics to reduce and regress atherosclerosis.

PMID- 30300748
TI  - Cationic carrier peptide enhances cerebrovascular targeting of nanoparticles in
      Alzheimer's disease brain.
AB  - Accumulation of amyloid beta (Abeta) peptides in the cerebral vasculature,
      referred to as cerebral amyloid angiopathy (CAA), is widely observed in
      Alzheimer's disease (AD) brain and was shown to accelerate cognitive decline.
      There is no effective method for detecting cerebrovascular amyloid (CVA) and
      treat CAA. The targeted nanoparticles developed in this study effectively
      migrated from the blood flow to the vascular endothelium as determined by using
      quartz crystal microbalance with dissipation monitoring (QCM-D) technology. We
      also improved the stability, permeability, and blood-brain barrier (BBB)
      transcytosis of targeted nanoparticles by coating them with a cationic BBB
      penetrating peptide (K16ApoE). The K16ApoE-Targeted nanoparticles demonstrated
      specific targeting of vasculotropic DutchAbeta40 peptide accumulated in the
      cerebral vasculature. Moreover, K16ApoE-Targeted nanoparticles demonstrated
      significantly greater uptake into brain and provided specific MRI contrast to
      detect brain amyloid plaques.

PMID- 30300749
TI  - Trimodal synergistic antitumor drug delivery system based on graphene oxide.
AB  - A multifunctional antitumor drug delivery system was synthesized based on
      graphene oxide (GO) for near-infrared (NIR) light controlling
      chemotherapeutic/photothermal (PTT) /photodynamic (PDT) trimodal synergistic
      therapy. The system named ICG-Wed-GO was formed by co-loading wedelolactone (Wed)
      and indocyanine green (ICG) on the surface of GO through pi-pi stacking
      interaction. Under NIR laser irradiation, ICG-Wed-GO could effectively absorb and
      transform optical energy to heat, generate reactive oxygen species (ROS) to
      ablating and damage tumor cells. The temperature of ICG-Wed-GO solution reached
      up to 79.4  degrees C in 10 min with NIR irradiation. In in vitro and in vivo
      study, ICG-Wed-GO showed excellent antitumor effect. After 14-day treatment of
      ICG-Wed-GO with NIR laser irradiation, the tumor disappeared completely on tumor
      bearing mice. The low biotoxicity of ICG-Wed-GO was also proved. The system
      achieved the synergistic trimodal chemotherapeutic/photothermal/photodynamic
      treatment and demonstrated excellent antitumor effect, which is expected to have
      a greater potential for cancer therapy.

PMID- 30300750
TI  - Self-assembling lisofylline-fatty acid conjugate for effective treatment of
      diabetes mellitus.
AB  - Lisofylline is an anti-inflammatory agent with proven anti-diabetic activity. Its
      high solubility and rapid metabolism results in poor bioavailability and short
      half-life, limiting its clinical utility. We have synthesized Lisofylline
      Linoleic acid (LSF-LA) conjugate which self-assembled into micelles (156.9 nm;
      PDI 0.187; CMC 1 MUg/mL; aggregation number 54) without any surfactant and showed
      enhanced cellular uptake. It protected MIN6 insulinoma cells from cytokine
      induced cell death and enhanced insulin production under inflammatory conditions.
      It also suppressed the proliferation of activated peripheral blood mononuclear
      cells and reduced the production of inflammatory cytokines, IFN-gamma and TNF
      alpha. LSF-LA micelles exhibited reduced protein binding, significantly higher
      half-life (5.7-fold) and higher apparent volume of distribution (5.3-fold) than
      free LSF. In T1D animals, reduced blood glucose levels were observed at a reduced
      dose (~15 mg/kg, once daily of LSF-LA micelles vs. 25 mg/kg, twice daily of free
      LSF) that was further confirmed by immunohistochemical analysis.

PMID- 30300751
TI  - Automatic segmentation of the spinal cord and intramedullary multiple sclerosis
      lesions with convolutional neural networks.
AB  - The spinal cord is frequently affected by atrophy and/or lesions in multiple
      sclerosis (MS) patients. Segmentation of the spinal cord and lesions from MRI
      data provides measures of damage, which are key criteria for the diagnosis,
      prognosis, and longitudinal monitoring in MS. Automating this operation
      eliminates inter-rater variability and increases the efficiency of large
      throughput analysis pipelines. Robust and reliable segmentation across multi-site
      spinal cord data is challenging because of the large variability related to
      acquisition parameters and image artifacts. In particular, a precise delineation
      of lesions is hindered by a broad heterogeneity of lesion contrast, size,
      location, and shape. The goal of this study was to develop a fully-automatic
      framework - robust to variability in both image parameters and clinical condition
      - for segmentation of the spinal cord and intramedullary MS lesions from
      conventional MRI data of MS and non-MS cases. Scans of 1042 subjects (459 healthy
      controls, 471 MS patients, and 112 with other spinal pathologies) were included
      in this multi-site study (n = 30). Data spanned three contrasts (T1-, T2-, and
      T2*-weighted) for a total of 1943 vol and featured large heterogeneity in terms
      of resolution, orientation, coverage, and clinical conditions. The proposed cord
      and lesion automatic segmentation approach is based on a sequence of two
      Convolutional Neural Networks (CNNs). To deal with the very small proportion of
      spinal cord and/or lesion voxels compared to the rest of the volume, a first CNN
      with 2D dilated convolutions detects the spinal cord centerline, followed by a
      second CNN with 3D convolutions that segments the spinal cord and/or lesions.
      CNNs were trained independently with the Dice loss. When compared against manual
      segmentation, our CNN-based approach showed a median Dice of 95% vs. 88% for
      PropSeg (p <= 0.05), a state-of-the-art spinal cord segmentation method.
      Regarding lesion segmentation on MS data, our framework provided a Dice of 60%, a
      relative volume difference of -15%, and a lesion-wise detection sensitivity and
      precision of 83% and 77%, respectively. In this study, we introduce a robust
      method to segment the spinal cord and intramedullary MS lesions on a variety of
      MRI contrasts. The proposed framework is open-source and readily available in the
      Spinal Cord Toolbox.

PMID- 30300753
TI  - High detection sensitivity with antibody-based PET radioligand for amyloid beta
      in brain.
AB  - PET imaging of amyloid-beta (Abeta) deposits in brain has become an important aid
      in Alzheimer's disease diagnosis, and an inclusion criterion for patient
      enrolment into clinical trials of new anti-Abeta treatments. Available PET
      radioligands visualizing Abeta bind to insoluble fibrils, i.e. Abeta plaques.
      Levels of prefibrillar Abeta forms, e.g. soluble oligomers and protofibrils,
      correlate better than plaques with disease severity and these soluble species are
      the neurotoxic form of Abeta leading to neurodegeneration. The goal was to create
      an antibody-based radioligand, recognizing not only fibrillary Abeta, but also
      smaller and still soluble aggregates. We designed and expressed a small
      recombinant bispecific antibody construct, di-scFv 3D6-8D3, targeting the Abeta N
      terminus and the transferrin receptor (TfR). Natively expressed at the blood
      brain barrier (BBB), TfR could thus be used as a brain-blood shuttle. Di-scFv 3D6
      8D3 bound to Abeta1-40 with high affinity and to TfR with moderate affinity. Di
      scFv [124I]3D6-8D3 was injected in two transgenic mouse models overexpressing
      human Abeta and wild-type control mice and PET scanned at 14, 24 or 72 h after
      injection. Di-scFv [124I]3D6-8D3 was retained in brain of transgenic animals
      while it was cleared from wild-type lacking Abeta. This difference was observed
      from 24 h onwards, and at 72 h, 18 months old transgenic animals, with high load
      of Abeta pathology, displayed SUVR of 2.2-3.5 in brain while wild-type showed
      ratios close to unity. A subset of the mice were also scanned with [11C]PIB.
      Again wt mice displayed ratios of unity while transgenes showed slightly, non
      significantly, elevated SUVR of 1.2, indicating improved sensitivity with novel
      di-scFv [124I]3D6-8D3 compared with [11C]PIB. Brain concentrations of di-scFv
      [124I]3D6-8D3 correlated with soluble Abeta (p < 0.0001) but not with total
      Abeta, i.e. plaque load (p = 0.34). We have successfully created a small
      bispecific antibody-based radioligand capable of crossing the BBB, subsequently
      binding to and visualizing intrabrain Abeta in vivo. The radioligand displayed
      better sensitivity compared with [11C]PIB, and brain concentrations correlated
      with soluble neurotoxic Abeta aggregates.

PMID- 30300754
TI  - Histoplamosis in an immunocompetent man returning from Brazil: A diagnostic
      challenge helped by 18 FDG PET CT.

PMID- 30300755
TI  - Microbiological features of indigenous typhoid cases in Taiwan and relatedness to
      imported cases, 2001-2014: A cross-sectional analysis.
AB  - BACKGROUND: Typhoid fever was rare in Taiwan but approximately two-thirds of the
      cases were indigenous. The transmission source of the indigenous cases and the
      relatedness to the imported cases remained unknown. METHODS: Patients with any
      site culture positive for Salmonella enterica serovar Typhi were identified in a
      teaching hospital during 2001-2014. The isolates were determined for antibiotic
      susceptibilities, pulsed-field gel electrophoresis (PFGE) types and single
      nucleotide polymorphisms (SNP) types. RESULTS: A total of 64 typhoid episodes
      were identified in 63 patients. Seventeen episodes (26.6%) were imported and a
      majority (10, 58.8%) of them were from Indonesia. The clinical manifestations,
      outcomes of patients and antibiograms of isolates were similar between indigenous
      and imported cases. 63.3% of the isolates were ciprofloxacin-resistant. The
      distributions of PFGE and SNP types did not differ significantly between
      indigenous and imported isolates, either (P = 0.191 and 0.124, respectively).
      Identical PFGE pattern could be identified in indigenous isolates appearing at
      certain time frames, indicating outbreaks due to local transmission of certain
      Typhi strains. CONCLUSIONS: The imported cases of typhoid fever from Southeast
      Asia were the major sources of indigenous S. Typhi infections in Taiwan. Small
      scale outbreaks occurred due to local transmission of the strains after their
      importation.

PMID- 30300752
TI  - A framework for linking resting-state chronnectome/genome features in
      schizophrenia: A pilot study.
AB  - Multimodal, imaging-genomics techniques offer a platform for understanding
      genetic influences on brain abnormalities in psychiatric disorders. Such
      approaches utilize the information available from both imaging and genomics data
      and identify their association. Particularly for complex disorders such as
      schizophrenia, the relationship between imaging and genomic features may be
      better understood by incorporating additional information provided by advanced
      multimodal modeling. In this study, we propose a novel framework to combine
      features corresponding to functional magnetic resonance imaging (functional) and
      single nucleotide polymorphism (SNP) data from 61 schizophrenia (SZ) patients and
      87 healthy controls (HC). In particular, the features for the functional and
      genetic modalities include dynamic (i.e., time-varying) functional network
      connectivity (dFNC) features and the SNP data, respectively. The dFNC features
      are estimated from component time-courses, obtained using group independent
      component analysis (ICA), by computing sliding-window functional network
      connectivity, and then estimating subject specific states from this dFNC data
      using a k-means clustering approach. For each subject, both the functional (dFNC
      states) and SNP data are selected as features for a parallel ICA (pICA) based
      imaging-genomic framework. This analysis identified a significant association
      between a SNP component (defined by large clusters of functionally related SNPs
      statistically correlated with phenotype components) and time-varying or dFNC
      component (defined by clusters of related connectivity links among distant brain
      regions distributed across discrete dynamic states, and statistically correlated
      with genomic components) in schizophrenia. Importantly, the polygenetic risk
      score (PRS) for SZ (computed as a linearly weighted sum of the genotype profiles
      with weights derived from the odds ratios of the psychiatric genomics consortium
      (PGC)) was negatively correlated with the significant dFNC component, which were
      mostly present within a state that exhibited a lower occupancy rate in
      individuals with SZ compared with HC, hence identifying a potential dFNC imaging
      biomarker for schizophrenia. Taken together, the current findings provide
      preliminary evidence for a link between dFNC measures and genetic risk,
      suggesting the application of dFNC patterns as biomarkers in imaging genetic
      association study.

PMID- 30300756
TI  - Occurrence of intestinal parasites among asylum seekers in Italy: A cross
      sectional study.
AB  - BACKGROUND: In recent years Europe has experienced a dramatic increase in
      migration flows. Nevertheless, limited data is available about the occurrence of
      neglected parasitic diseases among migrant population. The purpose of the present
      study was to evaluate the prevalence of intestinal and urinary parasites in newly
      arrived asylum seekers. METHODS: A total of 364 newly arrived migrants hosted at
      the Asylum Seekers Centre of Castelnuovo di Porto (Italy) were screened during 8
      months period for intestinal and urinary parasites. Each enrolled subject was
      interviewed using a standardized questionnaire, with focus on socio-demographical
      data and risk factors of parasitic infections. RESULTS: Stool analysis showed a
      prevalence of intestinal parasites of 20.6%. The travel route did not affect the
      prevalence of intestinal parasites (p = 0.096), while a significant negative
      correlation was found between the length of travel and the prevalence of parasite
      infection (p = 0.019). No statistically significant correlation between
      gastrointestinal symptoms and the presence of intestinal parasites was detected.
      CONCLUSION: The prevalence of intestinal parasitosis reported in asylum seekers
      does not necessarily reflect the prevalence of the parasitosis in the motherland.
      An anamnestic and syndromic approach may not be sufficient to highlight the
      problem of intestinal parasitic infestations in a screening setting.

PMID- 30300758
TI  - Transcriptomic changes in C2C12 myotubes triggered by electrical stimulation:
      Role of Ca2+i-mediated and Ca2+i-independent signaling and elevated [Na+]i/[K+]i
      ratio.
AB  - Elevation of Ca2+i and AMP-activated protein kinase (AMPK) are considered as
      major signals triggering transcriptomic changes in exercising skeletal muscle.
      Electrical pulse stimulation (EPS) of cultured myotubes is widely employed as an
      in vitro model of muscle contraction. This study examines the impact of Ca2+i
      mediated and Ca2+i-independent signaling in transcriptomic changes in EPS-treated
      C2C12 myotubes. Electrical pulse stimulation (40 V, 1 Hz, 10 ms, 2 h) resulted in
      [Ca2+]i oscillations, gain of Na+i, loss of K+i, and differential expression of
      3215 transcripts. Additions of 10 MUM nicardipine abolished [Ca2+]i oscillations
      but did not affect elevation of the [Na+]i/[K+]i ratio seen in EPS-treated
      myotubes. Differential expression of 1018 transcripts was preserved in the
      presence of nicardipine, indicating a Ca2+i-independent mechanism of excitation
      transcription coupling. Among nicardipine-resistant transcripts, we noted 113
      transcripts whose expression was also affected by partial Na+,K+-ATPase
      inhibition with 30 MUM ouabain providing the same elevation of the [Na+]i/[K+]i
      ratio as in EPS-treated cells. Electrical pulse stimulation increased
      phosphorylation of CREB, ATF-1, Akt, ERK, and p38 MAPK without any impact on
      phosphorylation of acetyl-CoA carboxylase and Unc-51 like autophagy activating
      kinase-1, i.e. downstream markers of AMPK activation. Unlike CREB, ATF-1, and
      MAPKs, an increment in Akt phosphorylation was abolished by nicardipine. Thus,
      our results show that Ca2+i-independent signaling plays a key role in altered
      expression of 30% of studied genes in EPS-treated myotubes. This signaling
      pathway is at least partially triggered by dissipation of transmembrane gradients
      of monovalent cations.

PMID- 30300759
TI  - Assembly and disassembly intermediates of maize streak geminivirus.
AB  - Maize streak virus (MSV) belongs to the Geminiviridae. Four forms of MSV coat
      protein (CP) assemblages were isolated from infected plants: geminate capsids, T
      = 1 icosahedral capsids, pentamers and decamers of CPs. Sequential exposure of
      geminate capsids to increasing pH, from 4.8 to 7.2 was used to monitor capsid
      disassembly. The capsids remain intact at pH4.8, disassemble to decamers and
      pentamers by pH6.4 and aggregate by pH7.2. Similarly, high salt and divalent
      cations cause disassembly. The disassembly process was reversed in low pH and low
      salt, but resulted in empty (no DNA) single and geminate capsid assemblies. This
      is likely due to disruption of CP-DNA interactions under acidic conditions and
      suggests a mechanism of capsid assembly in which the genome is packaged into
      preformed empty capsids. The pH assay developed in this study provides a method
      for characterizing the conditions that are the determinants of geminivirus
      assembly and disassembly.

PMID- 30300757
TI  - Modulation of associative learning in the hippocampal-striatal circuit based on
      item-set similarity.
AB  - Mounting evidence suggests that the medial temporal lobe (MTL) and striatal
      learning systems support different forms of learning, which can be competitive or
      cooperative depending on task demands. We have previously shown how activity in
      these regions can be modulated in a conditional visuomotor associative learning
      task based on the consistency of response mappings or reward feedback (Mattfeld &
      Stark, 2015). Here, we examined the shift in learning towards the MTL and away
      from the striatum by placing strong demands on pattern separation, a process of
      orthogonalizing similar inputs into distinct representations. Mnemonically,
      pattern separation processes have been shown to rely heavily on processing in the
      hippocampus. Therefore, we predicted modulation of hippocampal activity by
      pattern separation demands, but no such modulation of striatal activity. Using a
      variant of the conditional visuomotor associative learning task that we have used
      previously, we presented participants with two blocked conditions: items with
      high and low perceptual overlap during functional magnetic resonance imaging
      (fMRI). As predicted, we observed learning-related activity in the hippocampus,
      which was greater in the high than the low overlap condition, particularly in the
      dentate gyrus. In contrast, the associative striatum also showed learning related
      activity, but it was not modulated by overlap condition. Using functional
      connectivity analyses, we showed that the correlation between the hippocampus and
      dentate gyrus with the associative striatum was differentially modulated by high
      vs. low overlap, suggesting that the coordination between these regions was
      affected when pattern separation demands were high. These findings contribute to
      a growing literature that suggests that the hippocampus and striatal network both
      contribute to the learning of arbitrary associations that are computationally
      distinct and can be altered by task demands.

PMID- 30300760
TI  - Substance abuse in parents and subsequent risk of offspring psychiatric morbidity
      in late adolescence and early adulthood: A longitudinal analysis of siblings and
      their parents.
AB  - The effects of substance abuse on other family members are not fully established.
      We estimate the contribution of parental substance abuse on offspring psychiatric
      morbidity in late adolescence and early adulthood, with emphasis on the timing
      and persistency of exposure. We used a nationally representative 20% sample of
      Finnish families with children born in 1986-1996 (n = 136,604) followed up in
      1986-2011. We identified parental substance abuse and offspring psychiatric
      morbidity from hospital discharge records, death records and medication
      registers. The effects of parental substance abuse at ages 0-4, 5-9 and 10-14 on
      psychiatric morbidity after age 15 were estimated using population averaged and
      sibling fixed effects models; the latter controlling for unobserved factors
      shared by siblings. Parental substance abuse at ages 0-14 was associated with
      almost 2-fold increase in offspring psychiatric morbidity (HR = 1.86, 95% CI 1.78
      1.95). Adjustment for childhood parental education, income, social class and
      family type reduced these effects by about 50%, with some further attenuation
      after adjustment for time-varying offspring characteristics. In the sibling fixed
      effects models those exposed at 0-4 or 5-9 years had 20% (HR = 1.20, 95% CI 0.90
      1.60) and 33% (HR = 1.33, 95% CI 1.01-1.74) excess morbidity respectively. Also
      in sibling models those with early exposure at ages 0-4 combined with repeated
      exposure in later childhood had about 80-90% higher psychiatric morbidity as
      compared to never exposed siblings (e.g. for those exposed throughout childhood
      HR = 1.81, 95% CI 1.01-3.25). Childhood exposure to parental substance abuse is
      strongly associated with subsequent psychiatric morbidity. Although these effects
      are to a large extent due to other characteristics shared within the parental
      home, repeated exposure to parental substance abuse is independently associated
      with later psychiatric morbidity.

PMID- 30300761
TI  - Unexpected death in ill old age: An analysis of disadvantaged dying in the
      English old population.
AB  - The literature on death expectation in ill old age is mostly medical. A social
      science standpoint (especially quantitative) is practically absent. However,
      whether families, social and healthcare services can anticipate, support and
      prepare for the deaths of ill old adults is not reducible to the biomedical
      paradigm. Yet it is critical for end of life care (EOLC) policy. This study's aim
      is to investigate relatives' perception of death as unexpected in relation to
      both disease-related and care-related factors. Using the English Longitudinal
      Study of Ageing End-of-life Interviews Wave 6 this paper draws on probit
      regression analysis of unexpected (vs. expected) death in ill adults aged 50+.
      Findings are interpreted considering the containment of sudden death and the
      trajectories of dying in ill old age. The latter display overall visible decline
      preceding death. On this basis, EOLC literature and policy evidence death's
      uncertain timing as much as death's certain emergence in the horizon of
      expectation. Therefore, unexpected death in ill old age was interpreted as a
      failure to acknowledge dying, rather than the impossibility of discerning its
      approach. Very old age, dementia diagnoses and supported care environments were
      found to shape unexpected death.

PMID- 30300763
TI  - Investigation of flow characteristics in the maxillary sinus where polypoid
      changes develop.
AB  - Flow behavior in the maxillary sinus where polypoid changes develop was
      investigated using computational fluid dynamics. A nasal cavity model was
      constructed, after performing a virtual polypectomy based on computed tomography
      images of a patient, using a computer-aided design software to artificially
      remove polypoid changes inside the maxillary sinus. Local flow characteristics in
      the maxillary sinus were examined for one full respiration period. The results
      showed that the epithelial surfaces where polypoid changes occur are located in
      the lower part of the maxillary sinus which contains a protruding zone of the
      sinus and are characterized by stagnation of air during the entire respiration
      period. Due to the geometric characteristics, a very slow recirculating motion
      was found to occur in the bulging area for approximately half of the respiration
      period as a result of interaction with a larger-scale, counter-rotating vortex
      filling the middle of the maxillary sinus. With a much smaller velocity inside
      the maxillary sinus compared to that typically found in the airway passage
      through the middle meatus, both wall shear and pressure changes were found to be
      vanishingly small along the epithelial surface of the maxillary sinus where
      polypoid changes were found.

PMID- 30300762
TI  - Before the here and now: What we can learn from variation in spatiotemporal
      patterns of changing heart disease mortality by age group, time period, and birth
      cohort.
AB  - One hypothesized explanation for the recent slowing of declines in heart disease
      death rates is the generational shift in the timing and accumulation of risk
      factors. However, directly testing this hypothesis requires historical age-group
      specific risk factor data that do not exist. Using national death records, we
      compared spatiotemporal patterns of heart disease death rates by age group, time
      period, and birth cohort to provide insight into possible drivers of trends. To
      do this, we calculated county-level percent change for five time periods (1973
      1980, 1980-1990, 1990-2000, 2000-2010, 2010-2015) for four age groups (35-44, 45
      54, 55-64, 65-74), resulting in eight birth cohorts for each decade from the
      1900s through the 1970s. From 1973 through 1990, few counties experienced
      increased heart disease death rates. In 1990-2000, 49.0% of counties for ages 35
      44 were increasing, while all other age groups continued to decrease. In 2000
      2010, heart disease death rates for ages 45-54 increased in 30.4% of counties. In
      2010-2015, all four age groups showed widespread increasing county-level heart
      disease death rates. Likewise, birth cohorts from the 1900s through the 1930s
      experienced consistently decreasing heart disease death rates in almost all
      counties. Similarly, with the exception of 2010-2015, most counties experienced
      decreases for the 1940s birth cohort. For birth cohorts in the 1950s, 1960s, and
      1970s, increases were common and geographically widespread for all age groups and
      calendar years. This analysis revealed variation in trends across age groups and
      across counties. However, trends in heart disease death rates tended to be
      generally decreasing and increasing for early and late birth cohorts,
      respectively. These findings are consistent with the hypothesis that recent
      increases in heart disease mortality stem from the beginnings of the obesity and
      diabetes epidemics. However, the common geographic patterns within the earliest
      and latest time periods support the importance of place-based macro-level
      factors.

PMID- 30300764
TI  - Foot binding in a Ming dynasty cemetery near Xi'an, China.
AB  - This paper describes the morphology of the feet of a population of elite women
      from the Ming dynasty (1368-1644 CE) in Shaanxi province. This is a social
      stratum, time, and place in which foot binding was practiced. Among a group of 31
      skeletons exhumed from the cemetery, eight were women with well-preserved foot
      bones. Macroscopic examination revealed that half these women (4/8) had clearly
      altered foot bones: the metatarsal bones, and the few observable phalanges, were
      gracile and small, while the tarsal bones exhibited a slight reduction in size
      but no dramatic change in morphology. The other half of the women (4/8) had
      apparently unmodified metatarsal bones. T-tests comparing linear measurements of
      the foot bones between the two groups revealed that metatarsal bones were the
      most affected by binding, and among the tarsal bones, the talar trochlea and
      calcaneal dimensions were most impacted. This small group of skeletons reveals
      that some elite women in Shaanxi apparently still did not practice foot binding
      in the late Ming dynasty, or practiced a much milder form of foot binding, and
      that there was considerable variation even among those who did practice it.

PMID- 30300765
TI  - Radial Nerve Injury Caused by Compression Garment for Lymphedema: A Case Report.
AB  - Lymphedema is a condition characterized by localized fluid retention and tissue
      swelling caused by a compromised lymphatic system. To minimize fluid build-up and
      stimulate the flow of fluid through the lymphatic system, compression garments
      are usually applied to patients with lymphedema. There are few studies to report
      complications of compression garments to treat breast cancer-related lymphedema.
      To our knowledge, this is the first report of radial nerve compression neuropathy
      associated with wearing a compression garment to treat lymphedema.

PMID- 30300766
TI  - Venous Thromboembolism is Associated with Lack of Vitamin D Supplementation in
      Patients with Spinal Cord Injury and Low Vitamin D Levels.
AB  - BACKGROUND: The role of vitamin D (VitD) in the pathogenesis of venous
      thromboembolism (VTE) and prevalence of low VitD (LVitD) in spinal cord injury
      (SCI) has motivated VitD testing and supplementation. This is an exploratory
      study of data collected at a time before the routine clinical practice of VitD
      supplementation, allowing for evaluation of the natural history of LVitD levels
      in patients with SCI. OBJECTIVE: To determine if VitD supplementation in persons
      with SCI and LVitD levels is associated with decreased prevalence of VTE. DESIGN:
      Retrospective cohort study. SETTING: Rehabilitation Center at Level I Trauma
      Center. PARTICIPANTS: Patients with SCI admitted to acute inpatient
      rehabilitation (N=282). MAIN OUTCOME MEASURES: VTE prevalence in patients with
      LVitD levels, grouped by presence or absence of VitD supplementation. RESULTS: Of
      the acute inpatient SCI population, 80% (227/282) demonstrated VitD levels < 30
      ng/mL (LVitD). Although the incidence of VTE was almost double in the LVitD
      group, 19% (43/227) of the patients in the LVitD group had VTE versus 9% (5/55)
      of patients with VitD levels > 30 ng/mL (Normal VitD, NVitD), it did not achieve
      statistical significance (P=.108, V=.104). When the role of VitD supplementation
      was analyzed, individuals in the LVitD group who received no VitD supplementation
      (LVitDSuppNegative) had a statistically significant higher incidence of VTE
      compared to the LVitD group with VitD supplementation (LVitDSuppPositive) (24%
      [42/178] versus 2% [1/49]) (P<.001, V=.226). In post-hoc exploratory analyses,
      the VTE rate of patients in the LVitDSuppNegative group was noted to be
      significantly higher than all other patient groups combined (P<.001, V=.229). A
      binary logistic regression model incorporating clinical covariates also showed
      this grouping to be significant. CONCLUSION: A significant association appears to
      exist between lack of VitD supplementation and VTE occurrence in persons with
      acute SCI and LVitD levels.

PMID- 30300767
TI  - The Effectiveness of Injected Corticosteroid Type, Dose, and Volume for the
      Treatment of Pain in Small- and Intermediate-size Joints: A Systematic Review.
AB  - OBJECTIVE: To systematically evaluate the scientific literature examining the
      efficacy of corticosteroid injections in small- and intermediate-size joints,
      specifically looking at the effect of corticosteroid type, dose, and volume on
      clinical outcomes (pain and/or function). TYPE: Systematic review LITERATURE
      SURVEY: Medline (PubMed)(r), Cochrane Central Register of Controlled Trial, and
      SportDiscus(r) databases were searched. METHODOLOGY: Inclusion criteria included
      adult patients enrolled in prospective studies evaluating pain- and/or function
      related improvements following a corticosteroid injection of a small- or
      intermediate-sized joint. SYNTHESIS: A total of 28 articles were included in the
      study, all including patients with osteoarthritis and/or rheumatoid arthritis.
      Only six studies contained level I evidence, and most studies were prospective
      case series without a control. Most studies used 10-20mg of corticosteroid for
      small joints and 20-40mg in intermediate joints; wrist joints were the only joint
      studied that directly compared doses - 20mg was noninferior to 40mg.
      Triamcinolone hexacetonide was found to be superior to methylprednisolone in the
      interphalangeal finger joints; no other joints compared steroid types. No studies
      evaluated the effect of volume on clinical outcomes. Most studies showed pain
      and/or functional improvements for weeks to months. CONCLUSIONS: Very few studies
      directly examine the effect of corticosteroid type, corticosteroid dose, or
      injectate volume on clinical outcomes for small- or intermediate-size joint
      arthralgia. Future studies are needed to better elucidate the most effective
      treatment protocols. LEVEL OF EVIDENCE: Level II, systematic review of cohort
      studies.

PMID- 30300768
TI  - Palmaris Longus Tendinopathy Diagnosed with Ultrasound: A Case Report.
AB  - This is a case of 52-year old deaf female who was referred to the
      electrodiagnostic (EDX) laboratory for evaluation of pain and parasthesias in the
      left upper limb. The EDX study was normal. However, ultrasound revealed
      tendinopathy of the palmaris longus tendon, manifested by increased
      hypoechogenecity, caliber, and tenderness to sonopalpation compared to the right
      side. To the authors' knowledge there are no reported cases of palmaris longus
      tendinopathy diagnosed with ultrasound. This case supports the use of point of
      care ultrasound to explore other possible causes of pathology in patients with
      parasthesias in the context of a normal EDX study.

PMID- 30300769
TI  - Could the biomarker levels in saliva help distinguish between healthy implants
      and implants with peri-implant disease? A systematic review.
AB  - BACKGROUND: The most accurate data help to minimize possible mistakes on a
      patient's evaluation, as more robust findings are necessary to establish a
      correct diagnosis, prognosis and, consequently, better treatment. PURPOSE: Could
      biomarker levels in the saliva help to distinguish between healthy implants and
      implants with peri-implant disease? MATERIALS AND METHODS: An electronic database
      search of Pubmed/MEDLINE, Web of Science, the Cochrane Library, OVID and Scielo
      was performed. The articles and abstracts identified were considered relevant if
      they compared cytokine levels in saliva from patients with healthy implants to
      those in saliva from patients with untreated peri-implantitis. RESULTS: Lower
      salivary levels of interleukin 1beta were found in healthy implants than in
      inflamed implants. A significantly positive correlation was found between the
      salivary levels of IL-6 and peri-implant inflammatory conditions. The salivary
      concentrations of total antioxidants, urate and ascorbate were higher in healthy
      implants than in inflamed implants. The data extracted from the 6 studies
      evaluated in this review revealed heterogeneity in relation to the clinical
      parameters assessed, implant restoration, bone loss and peri-implant disease
      definitions. CONCLUSIONS: There was no clear, developed basis for using any
      specific biomarker in a clinical setting to distinguish between healthy implants
      and those with peri implant disease.

PMID- 30300770
TI  - In situ effect of fluoride toothpaste supplemented with nano-sized sodium
      trimetaphosphate on enamel demineralization prevention and biofilm composition.
AB  - OBJECTIVE: To evaluate the effect of a fluoride toothpaste containing nano-sized
      sodium trimetaphosphate (TMPnano) on enamel demineralization in situ and
      composition of the biofilm. DESIGN: This crossover double-blind study consisted
      of four phases (seven days each) and 12 volunteers who wore oral appliances
      containing four enamel bovine blocks. The cariogenic challenge was performed by
      30% sucrose solution (6x/day). The toothpaste treatments (3x/day) were as
      follows: no F/TMP/TMPnano (Placebo), 1100 ppm F (1100F), 1100F plus 3%
      micrometric or nano-sized TMP (1100F/TMP; 1100F/TMPnano). Percentage of surface
      hardness loss (%SH), and integrated loss of subsurface hardness (DeltaKHN), as
      well as enamel calcium (Ca), phosphorus (P), and fluoride (F) were determined.
      Moreover, biofilm formed on the blocks were analyzed for F, Ca, P, and insoluble
      extracellular polysaccharide (EPS) concentrations. Data were analyzed using one
      way ANOVA, repeated measures followed by Fisher LSD test (p < 0.001). RESULTS:
      1100F/TMPnano promoted the lowest %SH and DeltaKHN among all groups (p < 0.001).
      Regarding the F concentrations in the enamel and in the biofilm, there were no
      significant differences between 1100 F and 1100 F/TMPnano, but significantly
      increased enamel Ca concentrations (p < 0.001). 1100F/TMPnano showed lower values
      of EPS concentration when compared with 1100F (~80%) (p < 0.001). CONCLUSION:
      1100F/TMPnano promoted a greater protective effect against enamel
      demineralization and significantly affected the composition of biofilm formed in
      situ when compared to 1100F toothpaste.

PMID- 30300772
TI  - Fire safety enhancement of a highly efficient flame retardant
      poly(phenylphosphoryl phenylenediamine) in biodegradable poly(lactic acid).
AB  - Flame-retarded poly(lactic acid) (PLA) biodegradable materials are viewed as
      promising as sustainable alternatives to petroleum-based commodity polymers. A
      new highly efficient flame retardant, poly(phenylphosphoryl phenylenediamine)
      (PPDA), was synthesized by the condensation of phenylphosphoryl dichloride with p
      phenylenediamine and its structure was confirmed by 1H nulear magnetic resonance
      and Fourier-transform infrared spectroscopy. When 3 wt% PPDA was incorporated
      into PLA, the limited oxygen index increased from 20.0% of neat PLA to 25.5% and
      its UL-94 vertical burning testing achieved V-0 rating. Moreover, the total heat
      release and peak heat release rate values of PLA/3 wt% PPDA material were
      decreased from 109.1 MJ/m2 and 643.7 kW/m2 of PLA to 98.3 MJ/m2 and 570.0 kW/m2,
      respectively, and the fire performance index increased from 0.081 of PLA to 0.132
      m2 s/kW. The high fire safety of PPDA in PLA is mainly attributed to the combined
      effects of the phosphorous-containing radical inhibition and inert gases and the
      barrier action of the formed char layer. The addition of less than 3 wt% PPDA has
      little influence on the tensile and impact properties of PLA. The flame retardant
      PLA blends have great application potential in electrical casing, automobile
      interiors and three-dimensional printing materials.

PMID- 30300771
TI  - Management of non-metastatic castrate-resistant prostate cancer: A systematic
      review.
AB  - Management of non metastatic castrate resistant prostate cancer is challenging
      for clinicians due to the heterogeneity of the disease and to the scarce clinical
      data available in this setting. Recent results obtained with the new generation
      hormone therapies (NGHT) apalutamide and enzalutamide bring a new perspective for
      the treatment strategy. The authors present here a systematic review of the
      treatment options.

PMID- 30300773
TI  - Promotion of graphitic carbon oxidation via stimulating CO2 desorption by calcium
      carbonate.
AB  - Carbon oxidation has two stages, the first is the formation of surface oxides and
      the second is the gasification of the surface oxides to CO2. Calcium carbonate
      (CaCO3) was used to catalyze the gasification of the surface oxides. The
      catalytic effect of on graphite oxidation and its catalytic mechanism were
      studied by using thermogravimetric technique and in situ diffuse reflectance
      infrared Fourier transform spectroscopy (DRIFTS). It was found that
      characteristic temperature (T50) of graphite oxidation with CaCO3 was 946 K, 113
      K lower than that of graphite only. DRIFTS analysis results show that surface
      oxides (adsorbed CO2 and carbonate CO32-) were formed on the graphite surface at
      a temperature above 473 K, carbonate products on graphite surface disappeared
      when CaCO3 was present; formation of CO32- on CaCO3 surface was confirmed, this
      CO32- may be more easily gasified into gaseous CO2. The kinetic analysis results
      showed that CaCO3 promoted graphite oxidation has an activation energy of 74.3 kJ
      mol-1, far lower than that of graphite (148 kJ mol-1).

PMID- 30300774
TI  - Quantitative research on gas explosion inhibition by water mist.
AB  - Water mist as an effective explosion inhibitor has wide application prospect to
      prevent and reduce gas explosion hazard. The quantitative study of gas explosion
      inhibition with water mist provides the groundwork for the design of gas
      explosion suppression system. In this paper, the influence of the initial droplet
      sizes and spraying concentrations on explosion inhibition were numerically
      studied in a 2D numerical model. Under the initial spraying concentrations in the
      range of ~1.5 kg/m3, the inhibition effect of water mist on the explosion
      overpressure was not significant. The inhibition effect of water mist was mainly
      reflected in the suppression of the explosion flame temperature. When the initial
      droplet sizes were in the range of 50-150 MUm, the flame length was obviously
      reduced. But when the initial droplet sizes were less than 50 MUm or more than
      150 MUm, the inhibition to reduce flame length begin to weaken. The results of
      this study provide the theoretical basis of the suppression technology for gas
      explosion.

PMID- 30300775
TI  - Adducts formed during protein digestion decreased the toxicity of five carbonyl
      compounds against Caco-2 cells.
AB  - Acrolein (ACR), glyoxal (GO), methylglyoxal (MGO), hydroxymethylfurfural (HMF),
      and malondialdehyde (MDA) are toxic contaminants for humans. This work aimed to
      investigate whether intake of proteins can mitigate their toxicity. Simulated
      gastrointestinal digestion of proteins from pork, chicken, milk powder and soy
      protein isolate eliminated amount of ACR, GO, MGO, HMF, and MDA. Among six amino
      acids, cysteine showed highest capacity for elimination of these toxic compounds
      through the formation of adducts; it reached the highest elimination capacity for
      GO, MGO, ACR, MDA, and HMF in 40 min at pH 2.0, and 20 min at pH 7.0. The formed
      adducts between cysteine and GO, MGO, or ACR showed much lower toxicity against
      Caco-2 cells. Incubation of the cells with 8 mM GO and MGO for 48 h decreased the
      cell viability to 16.1%, 16.9% respectively; while incubation of the same
      concentration of their adducts still kept the cell viability at 82.2% and 81.6%
      respectively. Cysteine showed much higher detoxifying capacity for ACR than GO
      and MGO, which can lower the toxicity of ACR toward Caco-2 cells by 80 times.

PMID- 30300776
TI  - A unique Pb-binding flagellin as an effective remediation tool for Pb
      contamination in aquatic environment.
AB  - Metal contaminants present persistent and deleterious threats to environmental
      ecosystems and human health. Microorganisms can rapidly develop protective
      mechanisms against metal toxicity, such as metallothionein production. The
      identification of biological factors related to these protective mechanisms is
      essential for effective metal remediation. This study presents a robust pathway
      to rapidly locate and characterize a Pb-binding flagellin in Serratia Se1998,
      which can bind Pb at a 16:1 Pb: protein ratio. A column gel electrophoresis
      system hyphenated with inductively coupled plasma mass spectrometry (ICP MS) was
      constructed to efficiently separate and identify Pb-binding proteins from the
      whole bacterial proteome. PCR and transgenic assays were used to elucidate the
      exact sequences and biological function of Pb-binding proteins and heterogeneous
      expression of Pb-binding flagellin in E. coli could significantly enhance Pb
      removal from aqueous solution by approximately 45%. This method provides a
      benchmark procedure to rapidly identify biological factors responsible for metal
      biosorption. Identification of this unique Pb-binding flagellin highlights that
      microorganisms can survive high metal stresses due to various complex biological
      pathways for metal detoxification and remediation.

PMID- 30300777
TI  - Visible light promoted degradation of gaseous volatile organic compounds
      catalyzed by Au supported layered double hydroxides: Influencing factors,
      kinetics and mechanism.
AB  - In this paper, factors of initial concentration, catalyst dosage, irradiation
      intensity, relative humidity and reaction temperature onto visible light gaseous
      o-xylene photodegradation by ZnCr layered double hydroxides (ZnCr-LDHs) and Au
      supported ZnCr-LDHs (Au/ZnCr-LDHs) were investigated. ZnCr-LDHs shows low removal
      efficiency for o-xylene photodegradation, while Au/ZnCr-LDHs exhibits both
      excellent photodegradation rate and high TOF values for o-xylene as well as other
      VOCs including benzene, o-xylene, m-xylene and p-xylene. The kinetic equation and
      activation energy were calculated for o-xylene photodegradation, which are
      [Formula: see text] and 21.85 kJ/mol for ZnCr-LDH [Formula: see text] and 12.84
      kJ/mol for Au/ZnCr-LDHs. The obvious difference both in kinetic equation and
      activation energy suggests the reaction mechanism of ZnCr-LDHs and Au/ZnCr-LDHs
      should be very different. The active species inhabitation experiments show that
      the major drive of photocatalytic reaction for ZnCr-LDHs is hydroxyl radical,
      while for Au/ZnCr-LDHs it is the hole and hydroxide radical. It is also proved
      that the support of Au NPs onto LDHs would result in the transfer of photoexcited
      electrons from LDHs to Au NPs which results in the enhancement of photocatalytic
      property as well as photocatalytic mechanism change based on UV-vis, XPS, the
      contribution of different wavelength ranges of visible light onto photocatalytic
      efficiency and electrochemical tests.

PMID- 30300778
TI  - Reaction kinetics of phenols and p-nitrophenols in flowing aerated aqueous
      solutions generated by a discharge plasma jet.
AB  - In this paper, we propose a method for removing phenols and p-nitrophenols (PNPs)
      from flowing aqueous solutions generated by atmospheric pressure plasma jets
      (APPJs). For analyzing the removal characteristics, multiple techniques were
      used, including flow speed analysis of the aerated solution, optical emission
      spectroscopy (OES), and liquid chromatography. In addition, the reaction kinetics
      of diffusion and activation control processes were evaluated using aerated fluid
      speed variation and the corresponding activation energy. From these results, the
      relative intensities of hydroxyl radicals produced by an APPJ in water were found
      to be stronger than those in air and to decrease with increasing flow speed.
      Furthermore, the reaction kinetics were found to be diffusion-controlled when the
      solution flow speed was low and activation-controlled under high solution flow
      speed. It was also found that the degradation efficiency was enhanced with
      increasing flow speed, which increased the discharge voltage and temperature of
      the solution and changed the initial pH value when TiO2/UV catalysis was used.
      From the complex relationship between the reactive species, fluid diffusion, and
      discharge parameters in wastewater described herein, it is anticipated that these
      findings will facilitate new approaches to both the design and optimization of
      discharge reactors intended for wastewater treatment.

PMID- 30300779
TI  - Time of day effects on the relationship between daily sleep and anxiety: An
      ecological momentary assessment approach.
AB  - Previous research has linked sleep disturbance to anxiety. However, evidence for
      this relation has been inconsistent, largely limited to retrospective reports
      that do not account for daily variability, and silent on when the association is
      most pronounced. Thus, the present study utilized ecological momentary assessment
      (EMA) to examine the effects of daily deviations in total sleep time (TST) and
      person-average TST on anxiety and whether these effects varied as a function of
      time of day in a sample of unselected adults (N = 138). Results indicate that the
      amount of TST on a given night, relative to personal average TST, negatively
      predicted anxiety, and this relation was significant in the morning and
      afternoon, but not evening. In contrast, person-average TST was unrelated to
      average anxiety. Relations between TST and anxiety did not differ across
      objective (e.g., actigraphy) and subjective (e.g., sleep diary) measures.
      Furthermore, the pattern of results remained the same when controlling for
      previous day's anxiety and were not bidirectional. These findings suggest that
      getting less sleep than is typical for the individual predicts subsequent
      anxiety, and this effect is particularly strong in the morning. Average sleep
      duration may be less important to the experience of anxiety than deviations from
      that average. These findings highlight the importance of EMA to examine how and
      when variability in sleep confers vulnerability for anxiety symptoms.

PMID- 30300780
TI  - Effect of UV irradiation on iodinated trihalomethane formation during post
      chloramination.
AB  - Ultraviolet (UV) irradiation has been widely used in drinking water treatment
      processes, but its influence on the formation of disinfection by-products (DBPs),
      especially the emerging iodinated trihalomethanes (I-THMs) during post
      chloramination remains unclear. This study evaluated the impact of low pressure
      (LP) UV treatment on the formation of I-THMs during post-chloramination through
      two pathways. The first pathway is through the transition of DOM structure and
      composition during UV-chloramination, resulting significant increase of I-THM
      formation with increasing UV dosage in different dissolved organic matter (DOM)
      containing water (49.7%-90.5% at 1160 mJ/cm2). With the application of excitation
      emission matrix-parallel factor analysis (EEM-PARAFAC), we found that I-THM
      formation in UV-chloraminated water correlated well with two ratios of three
      PARAFAC humic-like components (C3/C2 and C1/C2, R2 = 0.958-1.000), suggesting
      that the ratios of fluorescent components can be used as reliable indicators for
      I-THM formation. Moreover, the shift in these fluorescent components is crucial
      for I-THM formation during UV-chloramination. Another pathway for UV irradiation
      to affect I-THM formation during post-chloramination is through the
      transformation of iodine species. Large amounts of reactive iodine species
      (HOI/I2 and I3-) can be generated directly in the mixed iodine system by UV
      light, leading to the enhancement of iodine utilization factor (IUF) (up to
      0.040) after post-chloramination. These results suggest that UV application to
      DOM-containing water may induce changes in organic precursors and iodine species
      so as to enhance I-THM formation during post-chloramination.

PMID- 30300781
TI  - Controlling effluent suspended solids in the aerobic granular sludge process.
AB  - The main processes contributing to elevated effluent suspended solids in the full
      scale aerobic granular sludge process were studied. The two processes found to be
      most important were (1) rising of sludge due to degasification of nitrogen gas
      (produced by denitrification) and (2) wash-out of particles that intrinsically do
      not settle such as certain fats and foams. A mathematical model was made to
      describe the process of degasification of nitrogen gas during the feeding phase
      in an AGS reactor. The process of rising sludge due to degasification could be
      limited by stripping out the nitrogen gas before starting the settling phase in
      the process cycle. The wash-out of scum particles could be reduced by introducing
      a vertical scum baffle in front of the effluent weir, similar to weirs in
      traditional clarifiers. A full-scale Nereda(r) reactor in the municipality of
      Utrecht, The Netherlands, was operated with a nitrogen stripping phase and scum
      baffles for 9 months at an average biomass concentration of 10 g L-1 and an
      average granulation grade of 84%. In this period the influent suspended solids
      concentration was 230+/-118mgL-1 and the concentration of effluent suspended
      solids was 7.8+/-3.8mgL-1.

PMID- 30300782
TI  - The role of surfactants in wastewater treatment: Impact, removal and future
      techniques: A critical review.
AB  - Wastewater treatment has an important responsibility to react to changing
      consumer and industrial produced wastes that pose environmental challenges.
      Surfactants are one of these emerging contaminants. They are of interest because
      of their increasingly ubiquitous domestic and industrial use and the difficulty
      their presence causes traditional treatment. In response to this developing area,
      this critical review considers research from a variety of technical backgrounds
      to provide an up to date overview of the impact of surfactants on the
      environment, health and their removal. This found major concerns about
      surfactants on the environment and on health being corroborated in the past five
      years. Current research into removal focuses on existing biological and chemical
      wastewater treatment optimisation. Despite improvements being found to
      traditional biological methods using chemical pre-treatments there is a clear
      lack of consensus regarding the ideal strategy. Drawbacks and potential solutions
      for a range of these technologies, including Fenton reaction and aerobic
      degradation, are discussed. In this field the authors recommend an improved
      diversity in surfactants used for the research and addressing of significant
      knowledge gaps. Novel methods, such as Carbon Nanotube (CNT) use are also
      discussed. These methods, while showing promising results, will require continual
      research effort to resolve present issues such as variable performance and
      environmental concerns. Larger scale work is also needed to validate the initial
      work done. Potential uses of surfactants to optimise wastewater treatment, such
      as Surfactant Modified Zeolites (SMZs), are also discussed. This review finds
      that surfactant removal from wastewater is a promising and challenging field that
      warrants further investigation.

PMID- 30300783
TI  - UV inactivation of human infectious viruses at two full-scale wastewater
      treatment plants in Canada.
AB  - Ultraviolet (UV) disinfection is widely used to inactivate microorganisms prior
      to release of treated municipal wastewater. However, limited data are available
      for in situ inactivation of infectious enteric viruses by UV treatment at full
      scale. In this study, a total of 51 pre-UV and 50 post-UV samples were collected
      over a two-year period from two wastewater treatment plants (WWTPs) and analyzed
      for noroviruses, rotavirus, reovirus, sapovirus, astrovirus, enteroviruses,
      adenoviruses and JC virus. Both pre-UV and post-UV samples had relatively high
      concentrations of these viruses determined by qPCR. Infectious viruses were also
      observed in 98% of pre-UV samples and 76% of post-UV samples by cell culture,
      using either cytopathic effect (CPE) or integrated cell culture with qPCR (ICC
      qPCR). Reovirus was the most common virus detected by ICC-qPCR, present in 92% of
      pre-UV and 48% of post-UV samples. Infectious enterovirus and adenovirus were
      detected by ICC-qPCR in 33% and 31% of pre-UV samples, 14% and 20% of post-UV
      samples, respectively. Mean log10 reduction estimates for infectious reovirus was
      1.2 and 1.8 log for the two WWTPs as assessed by ICC-qPCR, which was similar to
      the reduction of total infectious viruses (1.5 and 1.7 log) as assessed by CPE in
      cells culture. Overall, quantification of infectious reovirus appears to provide
      a useful index of enteric virus inactivation during wastewater treatment at full
      scale. To our knowledge, this is the first comprehensive study to assess UV
      inactivation of human enteric viruses at full-scale in WWTPs using both molecular
      and cell culture techniques, providing important information for quantitative
      microbial risk assessment of UV inactivation of human viruses in municipal
      wastewater.

PMID- 30300784
TI  - Non-activated peroxymonosulfate oxidation of sulfonamide antibiotics in water:
      Kinetics, mechanisms, and implications for water treatment.
AB  - Despite that sulfate radical-based activated peroxymonosulfate (PMS) oxidation
      processes (e.g., UV/PMS, Co2+/PMS, etc.) have been widely applied for
      decontamination, the direct oxidation of organic contaminants by PMS per se is
      less known. This contribution reports that certain contaminants, such as
      sulfonamides (SAs), are amendable to direct oxidation by PMS without activation.
      Using sulfamethoxazole (SMX) as a representative, kinetics and density functional
      theory (DFT)-based computational methods were applied to elucidate the underlying
      mechanisms and pathways through which SMX was transformed by direct PMS
      oxidation. High resolution mass spectrometry (HR-MS) coupled with high
      performance liquid chromatography (HPLC) analyses using authentic standards were
      adopted to qualifying and quantifying SMX transformation products. Our results
      reveal that nonradical oxidation of SMX by PMS was initiated by formation of a
      transition state complex between PMS molecule and amino functional group of SMX.
      Such reaction was assisted by two water molecules, which significantly reduced
      energy barrier. Direct PMS oxidation of SMX led to the formation of N4-hydroxyl
      sulfamethoxazole (N4-OH-SMX), 4-nitroso-sulfamethoxazole (4-NO-SMX), and 4-nitro
      sulfamethoxazole (4-NO2-SMX), sequentially. Implications of PMS oxidation with
      SAs to water treatment were further evaluated by investigating the effects of PMS
      dosage, pH, and natural water matrices. While PMS has a potential to transform a
      suite of SAs with similar structures (SMX, sulfisoxazole, sulfamethizole,
      sulfapyridine, sulfadiazine, and sulfachloropyridazine), the formation of
      potential hazardous nitroso- and nitro-byproducts should be scrutinized before
      this technology can be safely used for water and wastewater treatment.

PMID- 30300785
TI  - Removal of sulfonamide antibiotics and human metabolite by biochar and
      biochar/H2O2 in synthetic urine.
AB  - Source-separated urine has been increasingly regarded as a promising alternative
      waste-stream for effectively removing pharmaceuticals and human metabolites. This
      study investigated the removal of sulfonamide antibiotics, one category among the
      most frequently detected antibiotics in the environment, by biochar and
      biochar/H2O2 in synthetic urine matrix. The adsorption and degradation of four
      parent sulfonamide antibiotics, including sulfamethoxazole, sulfadiazine,
      sulfamethazine, sulfadimethoxine, and one human metabolite, N4-acetyl
      sulfamethoxazole (together referred as SAs) were investigated. Biochar derived
      from cotton straw was applied as adsorbent for SAs and catalyst for H2O2. Results
      showed that the adsorption of SAs was inhibited in urine compared with that in
      phosphate buffer solution. Bicarbonate in urine placed major influence. Langmuir
      isotherm model well described the adsorption process in both buffer and urine
      matrices. Adsorption and desorption rates were estimated by a kinetic model,
      which well fitted the removal of SAs from aqueous phase at various biochar doses.
      The adsorption of SAs on biochar was due to multiple forces, in which van der
      Waals forces and hydrophobicity played major roles in distinguishing the sorption
      behavior of different SAs. To destruct the SAs, H2O2 was added with biochar.
      Except for N4-acetyl-sulfamethoxazole, all the parent SAs can be degraded in
      urine matrix. Carbonate radical, produced from the activation of
      peroxymonocarbonate by biochar, was proposed to be the major contributing
      reactive species in biochar/H2O2 system in urine matrix.

PMID- 30300786
TI  - The evaluation of Oryza sativa L (Black rice) extracts for detection of
      spermatozoa on the clothing and vaginal swab samples.
AB  - Investigation of sexual assault cases from the evidence involving vaginal swab,
      clothing and others is examined by a forensic scientist. The explanation of trace
      findings on spermatozoa on clothing is often problematic due to the use of
      different staining methods. Conventional staining method used either Papanicolaou
      (PAP) or Dip quick(r) stain as synthetic dyes which are expensive imported
      material and harmful to human health. Therefore, the present study aims to
      determine the ability of Oryza sativa L (black rice) extract as a natural dye to
      detect spermatozoa on the clothing and vaginal swab casework samples for routine
      forensic examination. Results revealed that black rice extract has a highly
      effective for detecting spermatozoa on cloth and vaginal swab casework samples.
      There was no significantly different in the detection of spermatozoa compared
      with rapid PAP stain and Dip quick(r) stain. Results also showed that the
      staining of vaginal swab casework with black rice extracted can be used for PCR
      amplification of centromeric alphoid repeat gene on chromosome Y for 60 days.
      Moreover, the DNA extracted from stained semen slide generates a full profile of
      16 alleles of STR typing. The results indicate that a new natural staining dye
      which extracted from black rice can be used to detect spermatozoa and identify a
      person from the trace evidence. The application of natural dyes for routine
      staining of spermatozoa from forensic specimens will decrease the expense to be
      spent in purchasing the synthetic dye and reduce their side effects on human and
      environment.

PMID- 30300787
TI  - Recognition, treatment, and sequelae of congenital cytomegalovirus in Australia:
      An observational study.
AB  - BACKGROUND AND OBJECTIVES: Australian national surveillance data was used to
      assess recognition, sequelae, and antiviral therapy for congenital
      cytomegalovirus (CMV) cases. STUDY DESIGN: Data from congenital CMV cases
      reported through the Australian Paediatric Surveillance Unit born January 1999 to
      December 2016 were described and Chi-square tests used to characterise trends and
      associations in case reporting, maternal CMV serology testing, and antiviral
      therapy. Descriptive analyses for hearing loss and developmental delay were
      reported for cases born >=2004, following introduction of universal neonatal
      hearing screening. RESULTS: There were 302 congenital CMV cases (214 symptomatic,
      88 asymptomatic). Congenital CMV was suspected in 70.6% by 30 days of age, with
      no differences across birth cohorts. Maternal CMV serology testing was associated
      with maternal illness during pregnancy but not birth cohort. There was increasing
      antiviral use for symptomatic cases, being used in 14% born 1999-2004, 19.6% born
      2005-2010, and 44.4% born 2011-2016 (p < 0.001). For those born >=2004, hearing
      loss was reported in 42.1% of symptomatic and 26.6% of asymptomatic cases; while
      developmental delay was reported in 16.9% of symptomatic and 1.3% of asymptomatic
      cases. CONCLUSION: There appears to be under-reporting and under-recognition of
      congenital CMV despite increasing use of antiviral therapy. Universal newborn CMV
      screening should be considered to facilitate follow-up of affected children and
      targeted linkage into hearing and developmental services, and to provide
      population-level infant CMV epidemiology to support research and evaluation of
      antiviral and adjunctive therapies.

PMID- 30300788
TI  - CTRP5 promotes transcytosis and oxidative modification of low-density lipoprotein
      and the development of atherosclerosis.
AB  - BACKGROUND AND AIMS: Increased transcytosis of low-density lipoprotein (LDL)
      across the endothelium and oxidation of LDL deposited within the subendothelial
      space are crucial early events in atherogenesis. C1q/TNF-related protein (CTRP) 5
      is a novel secreted glycoprotein and its biological functions are largely
      undefined. METHODS: Expression of CTRP5 was analyzed in sera and atherosclerotic
      plaques of patients with coronary artery disease (CAD). The role of CTRP5 in
      atherogenesis was investigated in vitro and in vivo. RESULTS: We found CTRP5
      serum levels were higher in patients with than without CAD (247.26 +/- 61.71 vs.
      167.81 +/- 68.08 ng/mL, p < 0.001), and were positively correlated with the
      number of diseased vessels (Spearman's r = 0.611, p < 0.001). Increased
      expression of CTRP5 was detected in human coronary endarterectomy specimens as
      compared to non-atherosclerotic arteries. Immunofluorescence further showed that
      CTRP5 was predominantly localized in the endothelium, infiltrated macrophages and
      smooth muscle cells in the neointima. In vivo and in vitro experiments
      demonstrated that CTRP5 promoted transcytosis of LDL across endothelial
      monolayers, as well as the oxidative modification of LDL in endothelial cells.
      Mechanistically, we found that CTRP5 up-regulated 12/15-lipoxygenase (LOX), a key
      enzyme in mediating LDL trafficking and oxidation, through STAT6 signaling.
      Genetic or pharmacological inhibition of 12/15-LOX dramatically attenuated the
      deposition of oxidized LDL in the subendothelial space and the development of
      atherosclerosis. CONCLUSIONS: These data indicate that CTRP5 is a novel pro
      atherogenic cytokine and promotes transcytosis and oxidation of LDL in
      endothelial cells via up-regulation of 12/15-LOX.

PMID- 30300789
TI  - Trans-anal minimally invasive surgery: A new technique to avoid peritoneal entry.
AB  - INTRODUCTION: Transanal minimally invasive surgery (TAMIS) is a valuable surgical
      option for removal of rectal polyps and early rectal cancers. A potential
      complication of this technique is abdominal entry if the lesion is located above
      the peritoneal reflection. We present the first case series describing the use of
      a laparoscopic stapling device to remove a sessile lesion, and seal the resulting
      defect simultaneously with full thickness excision of the rectal lesion, avoiding
      abdominal entry. PRESENTATION OF CASES: Five patients with rectal lesions between
      8 and 14 cm from the anal verge are described in this case series. Each underwent
      a stapled-TAMIS procedure as the lesion was suspected to be above the peritoneal
      reflection. The goal specimen was achieved in each procedure. DISCUSSION: This
      article demonstrates the feasibility of a novel technique to remove sessile
      polyps in the upper rectum using laparoscopic staplers trans-anally through the
      TAMIS port. More studies and long-term follow-up are needed to evaluate the
      oncologic outcomes including the recurrence rate for those lesions removed with a
      stapler. CONCLUSION: For rectal lesions suspected to be above the peritoneal
      reflection, a stapled resection through a TAMIS port could prove be a valuable
      addition to the standard excisional approach to TAMIS.

PMID- 30300790
TI  - A rare case of paraganglioma of the cystic duct.
AB  - INTRODUCTION: Biliary system paragangliomas are rare neuroendocrine tumors of
      embryonic neural crest origin. The majority is asymptomatic and incidentally
      found due to gallbladder functional disorders. Herein, we present a non
      functional, 2.25 mm focus in the cystic duct, which to our knowledge, is the
      first reported paraganglioma of the cystic duct. PRESENTATION OF CASE: The
      patient presented to the Emergency Department complaining of a sudden-onset,
      right upper abdominal and epigastric pain. Ultrasound and Computed Tomography
      were both consistent with signs of early cholecystitis. Laparoscopic
      cholecystectomy was performed without major complications. In addition to
      cholelithiasis and chronic cholecystitis, pathological examination reported a
      neuroendocrine proliferation in the cystic duct measuring 2.25 mm favoring
      paraganglioma. Incidentally, the patient is unique in that they were also found
      to have an adrenal nodule and a normocalcemic primary hyperparathyroidism that
      raised suspicion for an underlying endocrinopathy. Nevertheless, genetic testing
      was negative. DISCUSSION: Extensive literature review demonstrates only nine
      cases of gallbladder paraganglioma, and three cases of hepatic ducts
      paraganglioma, but no cases of paraganglioma occurring at the cystic duct.
      Although a gene mutation and syndrome was not identified in the patient, the fact
      that an adrenal nodule and normocalcemic primary hyperparathyroidism were
      present, suggests that a complete hormonal workup should be obtained in these
      patients. CONCLUSION: It is important to realize that biliary system
      paragangliomas, although rare, may occur. As they have an association with
      multiple endocrine neoplasia syndrome, a thorough endocrine investigation should
      be made.

PMID- 30300791
TI  - A case report of a rare, spontaneous external jugular vein aneurysm.
AB  - INTRODUCTION: Compared to arterial aneurysms, venous pseudoaneurysms are rare and
      even more rare are external jugular vein aneurysms (EJV). To our knowledge, there
      are less than 10 well-documented cases of EJV aneurysms accessible. PRESENTATION
      OF CASE: Our patient is a 75 year old hispanic female who noticed a painless
      right neck mass two months prior. Ultrasound confirmed a cystic mass of unknown
      etiology containing doppler flow. Excisional biopsy revealed an EJV aneurysm with
      pathologic results of: blood, calcified debris, and a vessel wall consistent with
      EJV pseudoaneurysm. DISCUSSION: EJV aneurysms are clinically rare compared to IJV
      aneurysms. Recent trauma, cardiovascular disease and age are reported to be the
      highest significant clinical risk factors in the formation of jugular vein
      aneurism (JVA). The absence of trauma in our patient is noteworthy because it
      eliminates a direct contributor to a normally low-pressure vessel. CONCLUSIONS:
      Despite their rarity, spontaneous EJV aneurisms should be included in the
      differential of the elderly hypertensive patient who is presenting with a
      painless mass of the lateral neck that has cystic appearance and ultrasound
      findings of doppler flow.

PMID- 30300792
TI  - Effect of chitosan, and bacteriocin - Producing Carnobacterium maltaromaticum on
      survival of Escherichia coli and Salmonella Typhimurium on beef.
AB  - The aim of this study was to investigate the synergistic effect of chitosan and
      bacteriocins against Escherichia coli and Salmonella in media and in lean beef.
      The inhibitory effects of chitosan and bacteriocins against E. coli AW1.7 and S.
      enterica Typhimurium in media were determined by a critical dilution assay. The
      efficacy a bacteriocin-producing strain of Carnobacterium maltaromaticum and high
      molecular weight chitosan (HMWC) in inactivation of E. coli AW1.7 and S.
      Typhimurium was evaluated on beef. Current interventions applied in the beef
      industry, steaming coupled with lactic acid, were used as reference. HMWC
      demonstrated higher antibacterial activity than water soluble chitosan (WSC) or
      chitosan oligosaccharides (COS) in media, and the addition of partially purified
      bacteriocins from C. maltaromaticum UAL307 increased the activity of the chitosan
      in vitro. The hurdle combinations associated with HMWC inactivated E. coli AW1.7
      and S. enterica Typhimurium more effectively on lean beef when compared to steam
      or steam coupled with lactic acid. When used on beef, addition of bacteriocins
      and chitosan did not increase the antibacterial efficacy. Cell counts of S.
      enterica were further reduced during storage in presence of C. maltaromaticum and
      chitosan; however, this decrease was not dependent on bacteriocin production. In
      conclusion, addition of chitosan alone or in combination with C. maltaromaticum
      UAL 307 as protective culture significantly reduces cell counts of E. coli and
      Salmonella on beef. Results will be useful to improve pathogen intervention
      treatments in beef processing.

PMID- 30300793
TI  - Gene sequence screening for manganese poisoning-susceptible genes and analysis of
      gene interaction effects.
AB  - Manganese poisoning is a common occupational disease, studies have found that the
      susceptibility to manganese poisoning differs in individuals. We adopted genome
      wide sequencing methods to screen for susceptibility genes involved in gene
      mediated metabolic pathways from the perspective of manganese poisoning. We
      identified 18,439 genes in this study, including 14,272 known genes and 4398 new
      genes. We then selected 17 differential genes using p values, of which 7 genes
      were down-regulated and 10 genes were up-regulated. Possible interaction genes
      for each differential gene were selected according to the String database. Sgk1,
      HCRTr1, HspB1, Rem2, Oprd1, ATF5, and TRHr identified in this study may be
      involved in oxidative stress mechanisms, dopamine (DA) synthesis, and neuronal
      survival during apoptosis and may affect susceptibility to manganese poisoning.

PMID- 30300794
TI  - Dietary co-exposure to methylmercury and monosodium glutamate disrupts cellular
      and behavioral responses in the lobster cockroach, Nauphoeta cinerea model.
AB  - The present study aims to investigate the effect of monosodium glutamate (MSG)
      both separately and combined with a low dose of methylmercury (MeHg) on
      behavioral and biochemical parameters in Nauphoeta cinerea (lobster cockroach).
      Cockroaches were fed with the basal diet alone, basal diet + 2% NaCl, basal diet
      + 2% MSG; basal diet + 0.125 mg/g MeHg, basal diet + 0.125 mg/g MeHg + 2% NaCl;
      and basal diet + 0.125 mg/g MeHg + 2% MSG for 21 days. Behavioral parameters such
      as distance traveled, immobility and turn angle were automatically measured using
      ANY-maze video tracking software (Stoelting, CO, USA). Biochemical end-points
      such as acetylcholinesterase (AChE), glutathione-S-transferase (GST), total thiol
      and TBARS were also evaluated. Results show that MeHg + NaCl, increased distance
      traveled while MeHg + MSG increased time immobile. AChE activity was
      significantly reduced in cockroaches across all the groups when compared to the
      control. There was no significant alteration in GST activity and total thiol
      levels. It could be that both NaCl and MSG potentiates the neurotoxic effect of
      MeHg in cockroaches.

PMID- 30300795
TI  - Road safety and distraction, results from a responsibility case-control study
      among a sample of road users interviewed at the emergency room.
AB  - Despite the complexities of the driving task, more and more drivers engage in non
      driving secondary tasks that take their hands (manual distraction), their eyes
      (visual distraction) and/or their mind (cognitive distraction) away from their
      primary task. Inattention arising from external distractions has received much
      less consideration beyond the impact of mobile phone use. We aimed to investigate
      the association between distraction behind the wheel and risk of being
      responsible for a road traffic crash in a responsibility case-control study. The
      study population included 1912 drivers injured in a road traffic crash recruited
      in two rounds of recruitment (from April 2010 to August 2011 and from March 2013
      to January 2015) in the adult emergency department of Bordeaux University
      Hospital (France). Responsibility levels were estimated using a standardized
      method. Self-reported activities among a pre-established list of potential
      distractions were combined into four external distraction variables: visual
      distraction, manual distraction, auditory distraction, and verbal interaction. A
      significantly increased risk of being responsible for a road traffic crash was
      associated with the exposure to activities that take drivers' eyes off the road
      (adjusted odds ratio 2.99, 95% confidence interval 1.42-6.28) and activities that
      take drivers' hands off the wheel (adjusted odds ratio 2.12, 95% confidence
      interval 1.20-3.75). No significant associations were found for verbal
      interaction and listening to the radio and/or singing. This study suggests that
      beyond the use of mobile phone, particular attention must be paid to activities
      that involve visual and/or manual distraction.

PMID- 30300796
TI  - Reducing intercity bus crashes through driver rescheduling.
AB  - Intercity bus crashes often involve driver fatigue, which itself is usually the
      result of sleep deprivation, long driving hours, a maladjusted circadian rhythm,
      or some combination of the above. And driver scheduling has long been suspected
      as the root cause affecting sleepiness and fatigue. As such, a fundamental
      question for intercity bus carriers is how to reduce crashes associated with
      driver schedules, while maintaining a nonstop service? This research seeks to
      develop a paradigm to minimize overall fleet crash risk by rescheduling. In this
      study, we first identified those driving schedules associated with the highest
      crash risks, and a rescheduling scheme is then proposed to reduce fleet crashes
      overall. A case-study approach was employed to identify driver scheduling
      associated with higher crash risk, and a mathematical program was then formulated
      to minimize fleet crash risk. Our results showed that several types of driver
      schedules would lead to higher crash risk; for example: (1) working in the
      afternoon or early hours in the morning for two consecutive days; and (2)
      commencing a driving shift in the mornings, the afternoon or the early hours of
      the morning after being off-duty for more than 24 h. To meet the challenge of
      maintaining a nonstop service while simultaneously minimizing the crash risk
      associated with these risk patterns, a mathematical program was developed, and it
      was found that rescheduling based on our algorithm could reduce the incidence of
      crashes by approximately 30 percent.

PMID- 30300797
TI  - Who is responsible for global road safety? A cross-cultural comparison of Actor
      Maps.
AB  - The traditional three 'E's approach to road safety (engineering, education,
      enforcement) has had, and will continue to have, a significant impact on road
      traffic casualty rates worldwide. Nevertheless, with rising motorisation in many
      countries, global fatality numbers have changed little over the past decade.
      Following calls for the application of sociotechnical systems thinking to the
      problem, we widen the road safety discussion with an additional four 'E's;
      economics, emergency response, enablement, and, the umbrella term for the
      approach taken, ergonomics. The research presents an application of Rasmussen's
      Risk Management Framework to the road safety systems of five distinct nations;
      Bangladesh, China, Kenya, the UK, and Vietnam. Following site visits, reviews of
      literature, and interviews with subject matter experts in each of the countries,
      a series of Actor Map models of the countries' road safety systems were
      developed. These are compared and discussed in terms of the wide variety of
      interconnecting organisations involved, their influences on road safety outcomes,
      the differences between nations, and the need to look beyond road users when
      designing road safety interventions.

PMID- 30300799
TI  - Harm perceptions of electronic cigarettes and nicotine: A nationally
      representative cross-sectional survey of young people in Great Britain.
AB  - BACKGROUND: E-cigarettes often contain nicotine without the most harmful
      constituents of tobacco smoke. AIMS: This study aims to assess prevalence and
      correlates of accurately perceiving e-cigarettes as less harmful than cigarettes
      and that none or a small amount of the harm from smoking comes from nicotine.
      METHODS: Cross-sectional survey of 2,103 11-18-year-olds in Great Britain in
      2016. Prevalence of e-cigarette and nicotine harm perceptions were calculated.
      Logistic regressions assessed associations between accurate e-cigarette and
      nicotine harm perceptions and smoking, e-cigarette use, gender, age, region,
      social grade, family smoking, family e-cigarette use, smoking friends, public
      approval of smoking, and public approval of e-cigarettes. Associations between
      accurate e-cigarette and nicotine harm perceptions were also assessed. RESULTS:
      Most (63.4%) accurate e-cigarette harm perceptions were higher among those aged
      16+ (OR = 1.89 [95%CI = 1.45-2.47]), 14-15 (OR = 1.29 [1.00-1.65]), who
      tried/used an e-cigarette sometimes (OR = 1.51 [1.03-2.21]), with family e
      cigarette use (OR = 2.11 [1.46-3.04]), who perceived public disapproval of
      smoking (OR = 2.11 [1.18-3.77]) and approval of e-cigarettes (OR = 2.44 [1.73
      3.45]), and with accurate nicotine harm perceptions (OR = 2.05 [1.28-3.28]).
      Accurate nicotine harm perceptions were higher among those aged 16+ (OR = 2.60
      [1.62-4.16]), from North England (OR = 1.87 [1.02-3.43]) and Wales/Scotland (OR =
      2.61 [1.35-5.03]) vs. London, with family smoking (OR = 1.59 [1.05-2.42]), and
      with accurate e-cigarette harm perceptions (OR = 2.12 [1.32-3.41]). CONCLUSIONS:
      Many young people have inaccurate harm perceptions of e-cigarettes and nicotine.
      Accurate e-cigarette and nicotine harm perceptions were associated with one
      another. E-cigarette use was associated with accurate e-cigarette but not
      nicotine harm perceptions; smoking was not associated with either.

PMID- 30300798
TI  - Using single cell analysis for translational studies in immune mediated diseases:
      Opportunities and challenges.
AB  - The difficulty of studying small tissue samples and rare cell populations have
      been some of the main limitations in performing efficient translational studies
      of immune mediated diseases. Many of these conditions are grouped under the name
      of a single disease whilst there are strong suggestions that disease
      heterogeneity leads to variable disease progression as well as therapeutic
      responses. The recent development of single cell techniques, such as single cell
      RNA sequencing, gene expression profiling, or multiparametric cytometry, is
      likely to be a turning point. Single cell approaches provide researchers the
      opportunity to finally dissect disease pathology at a level that will allow
      mechanistic classifications and precision therapeutic strategies. In this review,
      we will give an overview of the current and developing repertoire of single cell
      techniques, the benefits and limitations of each, and provide an example of how
      single cell techniques can be utilized to understand complex immune mediated
      diseases and their translation from mouse to human.

PMID- 30300801
TI  - Non-medical use of prescription drugs and cultural orientation among college
      students in China.
AB  - BACKGROUND: Due to a dramatic increase in the past 20 years, the non-medical use
      of prescription drugs (NMUPD) has become a global public health issue. College
      students have high prevalence of NMUPD in the United States. However, limited
      studies have been conducted among Chinese students. The purposes of this study
      were to examine the prevalence of NMUPD among college students in two urban
      centers (Beijing and Macau) in China and assess its relationships with cultural
      orientation (collectivism - primary focus on the group and individualism -
      primary focus on the individual). METHODS: In January-April 2017, 849
      undergraduates (72.2% female) from Beijing and Macau, with an average age of 20
      completed online surveys about their demographics, NMUPD, and cultural
      orientation. RESULTS: Overall, 62.9% (lifetime) and 33.4% (past three-months) of
      students in Beijing reported NMUPD, while 35.9% (lifetime) and 21.8% (past three
      months) of students in Macau reported NMUPD. The most commonly non-medically used
      class of medicine (lifetime) was analgesics (62.9% Beijing; 35.5% Macau),
      followed by sedatives (4.0% Beijing; 0.9% Macau), anxiolytics (2.7% Beijing; 0.6%
      Macau), and stimulants (1.0% Beijing; 0.2% Macau). Multivariate analyses
      suggested a positive association of individualism with lifetime NMUPD (OR = 1.78,
      95% CI = 1.15, 2.75, p < .01 in Beijing; OR = 1.53, 95% CI = 1.16, 2.02, p < .01
      in Macau). CONCLUSION: NMUPD in Chinese college students appears to be common.
      More discussion is needed in China about regulation of prescription drugs. Future
      culturally-tailored NMUPD-risk reduction intervention programs may be beneficial
      to Chinese college students.

PMID- 30300800
TI  - Accounting for the uncounted: Physical and affective distress in individuals
      dropping out of oral naltrexone treatment for opioid use disorder.
AB  - BACKGROUND: The theoretical benefits of naltrexone as a treatment for opioid use
      disorder (e.g., safety, non-addictive, low risk of diversion) stand in sharp
      contrast to its disappointing record on retention in most samples. The
      relationship of uncomfortable physical and dysphoric symptoms to retention on
      naltrexone is a controversial and under-studied issue. METHODS: Using data from a
      randomized controlled trial of voucher-based contingency management and support
      from a significant other to enhance retention on oral naltrexone, we compared
      self-reported somatic and dysphoric symptoms, measured weekly, for individuals
      who were retained on naltrexone through the 12-week trial (n = 50) versus those
      who dropped out (n = 70). RESULTS: There were no differences between participants
      who completed treatment and those who dropped out on multiple baseline
      characteristics, including somatic or affective symptoms prior to treatment.
      However, whether analyzed cross-sectionally or over time, participants who
      dropped out consistently reported higher rates of somatic symptoms, particularly
      difficulty sleeping, as well as affective symptoms, including multiple indicators
      of depression, anxiety, and anhedonia. CONCLUSIONS: Although the smaller group of
      participants who were retained on oral naltrexone for 12 weeks reported
      decreasing physical and affective discomfort over time, there was substantial
      evidence that those who dropped out experienced continued and significant levels
      of distress. Individuals who report physical or affective distress while taking
      naltrexone may be at higher risk of dropout.

PMID- 30300802
TI  - Cigarette smoking is associated with cortical thinning in anterior frontal
      regions, insula and regions showing atrophy in early Alzheimer's Disease.
AB  - BACKGROUND: Magnetic resonance imaging studies of cigarette smoking-related
      effects on human brain structure primarily focused on cortical volumes. Much less
      is known about the effects of smoking on cortical thickness. Smokers and Non
      smokers were compared on regional cortical thickness. We predicted smokers would
      demonstrate greater age-related thinning localized to anterior frontal regions
      that serve as nodes for the executive, salience, and emotional regulation
      networks (ESER regions) and those demonstrating significant atrophy in early
      Alzheimer's Disease (AD regions). METHODS: Non-smokers (n = 41) and smokers (n =
      41), 22-70 years of age, completed a 4 T MRI study. Regional cortical thickness
      was quantitated via FreeSurfer. In smokers, associations between smoking
      severity, decision-making, impulsivity, and regional cortical thickness were
      examined. RESULTS: Smokers demonstrated cortical thinning in the medial and
      lateral OFC, insula, entorhinal, fusiform, middle temporal, and Composite AD
      regions. In Smokers, greater pack-years were associated with thinner lateral OFC,
      middle temporal, inferior parietal, fusiform, precuneus, and Composite AD
      regions. In Smokers, poorer decision-making/greater risk taking was related to
      thinner cortices in caudal ACC, rostral middle frontal and superior frontal gyri,
      and Composite ESER. Higher self-reported impulsivity was associated with thinner
      rostral and caudal ACC. CONCLUSIONS: This study provides additional evidence that
      cigarette smoking is associated with thinner cortices in regions implicated in
      the development and maintenance of substance use disorders and in regions
      demonstrating significant atrophy in early AD. The novel structure-function
      relationships in Smokers further our understanding of the neurobiological
      substrates potentially underlying the neuropsychological abnormalities documented
      in smokers.

PMID- 30300803
TI  - Assessment of rimonabant-like adverse effects of purported CB1R neutral
      antagonist / CB2R agonist aminoalkylindole derivatives in mice.
AB  - BACKGROUND: Cannabinoids may be useful in the treatment of CNS disorders
      including drug abuse and addiction, where both CB1R antagonists / inverse
      agonists and CB2R agonists have shown preclinical efficacy. TV-5-249 and TV-6-41,
      two novel aminoalkylindoles with dual action as neutral CB1R antagonists and CB2R
      agonists, previously attenuated abuse-related effects of ethanol in mice.
      PURPOSE: To further characterize these drugs, TV-5-249 and TV-6-41 were compared
      with the CB1R antagonist / inverse agonist rimonabant in assays relevant to
      adverse effects and cannabinoid withdrawal. PROCEDURES AND FINDINGS: The
      cannabinoid tetrad confirmed that TV-5-249 and TV-6-41 were devoid of CB1R
      agonist effects at behaviorally-relevant doses, and neither of the novel drugs
      induced rimonabant-like scratching. Generalized aversive effects were assessed,
      and rimonabant and TV-5-249 induced taste aversion, but TV-6-41 did not. Schedule
      controlled responding and observation of somatic signs were used to assess
      withdrawal-like effects precipitated by rimonabant or TV-6-41 in mice previously
      treated with the high-efficacy CB1R agonist JWH-018 or vehicle. Rimonabant and TV
      6-41 dose-dependently suppressed response rates in all subjects, but TV-6-41 did
      so more potently in JWH-018-treated mice than in vehicle-treated mice, while
      rimonabant equally suppressed responding in both groups. Importantly, rimonabant
      elicited dramatic withdrawal signs, but TV-6-41 did not. CONCLUSIONS: These
      findings suggest differences in both direct adverse effects and withdrawal
      related effects elicited by rimonabant, TV-5-249, and TV-6-41, which could relate
      to neutral CB1R antagonism, CB2R agonism, or a combination of both. Both
      mechanisms should be explored and exploited in future drug design efforts to
      develop pharmacotherapies for drug dependence.

PMID- 30300804
TI  - Association between the splice mutation g.8283C>A of the PHKG1 gene and meat
      quality traits in Large White pigs.
AB  - Pork technological and sensory qualities are greatly affected by water-holding
      capacity (WHC), pH, color, tenderness, and chemical composition, and the
      identification of genetic markers affecting these traits is regarded as a primary
      goal in pig selection. Phosphorylase Kinase Catalytic Subunit Gamma 1 (PHKG1)
      gene has been reported in the literature to be a candidate gene for meat drip
      loss, ultimate pH, color and glycolytic potential. This study was mainly aimed at
      testing whether PHKG1 g.8283C>A SNP was associated with meat quality traits in
      heavy pigs. The associations between PHKG1 g.8283C>A SNP, WHC, meat color and pH
      measurements were evaluated in 250 Italian Large White pigs. The marker showed an
      additive effect on WHC (P = .008) and a dominant effect on a* color parameter (P
      = .004). Further studies are needed to elucidate the effects of this polymorphism
      on heavy pig meat quality traits before this mutation could be considered a
      marker of interest for heavy pig selection schemes.

PMID- 30300805
TI  - Balance highly influences flexibility measured by the toe-touch test.
AB  - Flexibility evaluation is a standard assessment in clinical and in sports
      settings. The Toe-touch test (TTT) is a common assessment tool to evaluate
      posterior muscular chain flexibility, but the test procedure implies a balance
      demand. The objective of the study was to verify the hypothesis that the balance
      demand during the TTT may affect the flexibility measured by the test. Twenty
      healthy, active young adults participated in the present study. Toe-touch test
      outcome (the linear finger to toe distance), Center of Pressure (CP) and sagittal
      plane joint angles were compared under two balance conditions: (1) standard TTT
      (ST) and (2) minimised postural demand (MPD) during TTT (using a device that
      restrained the participant against a forward fall). Then, ST was re-tested to
      verify a possible effect of motor learning on TTT outcome. Compared to ST, MPD
      showed an improvement of 73% in test outcome, greater flexion of the ankle,
      greater total body flexion, and a forward displacement of the CP. Re-test of ST
      showed indications of motor learning with a different balance strategy compared
      to the first trial in the same condition. The test outcome showed significant
      negative correlations with CP position in ST (weak correlation), in the re-test
      (strong correlation) and when the conditions were combined (moderate
      correlation). In conclusion, TTT outcome was highly affected by balance
      performance. Maximum range of motion during ST was a fraction of the range
      obtained when balance demand was minimized.

PMID- 30300806
TI  - Removal of micropollutants and cyanobacteria from drinking water using KMnO4 pre
      oxidation coupled with bioaugmentation.
AB  - Increasing micropollutant and cyanobacterial contamination of drinking water
      threatens human health worldwide. However, these contaminates are not efficiently
      removed by common drinking water treatment processes, and thus additional
      treatments are frequently required. Recent investigations have demonstrated that
      KMnO4 pre-oxidation can efficiently remove some micropollutants and cyanobacteria
      but the release of cyanobacterial toxins and Mn2+ limit its use. To overcome
      these problems, we proposed a KMnO4 pre-oxidation coupled with bioaugmentation
      (e.g., sand filtration) method to treat micropollutant- and cyanobacteria-laden
      water. We used 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (BP-4, a common
      micropollutant in drinking water sources) and Microcystis aeruginosa (a widely
      distributed cyanobacterial species) as model pollutants to verify the feasibility
      of the proposed method. Results revealed that KMnO4 pre-oxidation efficiently
      removed existing natural organic matter and Microcystis aeruginosa but failed to
      remove BP-4 and released Mn2+ and microcystin-LR (MC-LR) during treatment.
      Following the addition of a manganese-oxidizing bacterial strain (Pseudomonas sp.
      QJX-1) to the KMnO4-treated solution, we found that the bacteria could transform
      Mn2+ to Mn(III&IV) oxides, with the formed Mn oxides then able to remove BP-4 and
      MC-LR. Overall, the proposed method exhibited advantages in the removal of
      natural organic matter (i.e., decreasing disinfection byproduct formation),
      micropollutants, and cyanobacteria as well as preventing the release of Mn2+, and
      thus may be considered a good alternative for treating polluted drinking water.

PMID- 30300807
TI  - Mechanisms of strontium's adsorption by Saccharomyces cerevisiae: Contribution of
      surface and intracellular uptakes.
AB  - The objective of this work was to explore the mechanisms participating in
      strontium sorption by living Saccharomyces cerevisiae (S. cerevisiae). The
      location of strontium adsorbed by S. cerevisiae was studied by our plasmolysis
      treatment. The contribution of physical and chemical mechanisms was determined
      quantitatively by desorption and blockage of functional groups. Moreover, our
      results indicated that bioaccumulation also played a major role in biosorption by
      living cells. Thus, supplementary methods including 2-DE (two-dimensional
      electrophoresis) and Matrix-Assisted Laser Desorption/Ionization Tandem Time of
      Flight Mass Spectrometry (MALDI-TOF-TOF) were employed to analyze the different
      proteins. The subsequent desorption % of Sr2+ by Distilled Water (DW), NH4NO3 and
      EDTA-Na2 from Sr2+ loaded sorbents indicated a minor role for physical
      adsorption, while ion exchange and complexation were responsible for
      approximately 20% and 40%. Specific blockage of functional groups revealed that
      carboxyl and amine groups played an important role in Sr2+ binding to the living
      S. cerevisiae. From our MALDI-TOF-TOF results, we concluded that 38 proteins
      showed up-regulated expression profiles and 11 proteins showed down-regulated
      after biosorption. Moreover, proteins belong to: phagocytic function (Act1p); ion
      channel (S-adenosylmethionine synthase); glycolysis (Tubulin) may directly
      involve in strontium bioaccumulation. In conclusion, the present work indicates
      that the strontium sorption mechanism by living S. cerevisiae is complicated
      including ion-exchange along with complexation as the main mechanism, whereas the
      other mechanisms such as physical adsorption play a minor contribution.
      Metabolically-dependent proteins may play an important role in bioaccumulation.

PMID- 30300808
TI  - Sorption and desorption of phenanthrene on biodegradable poly(butylene adipate co
      terephtalate) microplastics.
AB  - Biodegradable plastics, as alternatives to conventional plastics, are
      increasingly used, but their interactions with organic pollutants are still
      unknown. In this study, the sorption and desorption behaviors on a type of
      biodegradable plastic-poly(butylene adipate co-terephtalate) (PBAT) were
      investigated, and at the same time two types of conventional plastics
      polyethylene (PEc and PEv) and polystyrene (PS) were used for comparison.
      Phenanthrene (PHEN) was chosen as one of representative organic pollutants.
      Results indicated that the sorption and desorption capacities of PBAT were not
      only higher than those of the other types of microplastics, but also higher than
      those of carbonaceous geosorbents. The surface area normalized results
      illustrated that sorption and desorption of the microplastics were positively
      correlated with their abundance of rubbery subfraction. The sorption kinetic
      results showed that the sorption rates of PBAT and PEc were higher than PEv and
      PS. The effects of water chemistry factors including salinity, dissolved organic
      matter and Cu2+ ion on the sorption process displayed the same trend, but the
      degrees of influence on the four microplastics differed. The degrees of influence
      were mainly dependent on the abundance of rubbery subfraction for microplastics.
      These findings indicate that the biodegradable poly(butylene adipate co
      terephtalate) microplastics are actually stronger vectors than the conventional
      microplastics, and crystallization characteristics of the microplastics have
      great influences on the vector effect.

PMID- 30300809
TI  - Intermittent operating characteristics of an ecological soil system with two
      stage water distribution for wastewater treatment.
AB  - Ecological soil systems (ESSs) are usually used to remove nitrogen from
      wastewater. Due to the poor denitrification performance of traditional ecological
      soil systems (ESSs), this study proposes a two-stage water distribution system to
      improve the nitrogen removal. The effects of different distribution ratios on the
      system treatment effect were studied in an intermittent operation mode. After
      determining the optimal distribution ratio and intermittent operation conditions,
      the dynamics of system inflow, outflow, and nitrogen removal were monitored.
      Theoretical analysis of the denitrification mechanism was carried out. The
      results showed that the optimum water distribution ratio was 2: 1, and a mean
      total nitrogen removal rate of 60.42% was achieved, which is 23.09% greater than
      that is typically achieved by the single-section ecological system. Under optimum
      distribution ratio conditions, the system also demonstrated effective removal of
      chemical oxygen demand (COD), total phosphorus (TP) and ammonia nitrogen (NH4+
      N), allowing the effluent to satisfy China's urban sewage treatment plant level B
      emission standards.

PMID- 30300810
TI  - The effect of flunixin meglumine, firocoxib and meloxicam on the uterine mobility
      of equine embryos.
AB  - Embryo mobility occurs as a result of prostaglandin production by the embryo and
      endometrium, promoting uterine smooth muscle contractions, which propels the
      embryonic vesicle through the lumen. Non-steroidal anti-inflammatory drugs
      (NSAIDs), as flunixin meglumine, are routinely used in equine medicine and can
      alter the conceptus mobility if applied in early pregnancy, which may impair
      maternal recognition of pregnancy. The objective of this study was to evaluate
      and compare the effect of flunixin meglumine (FM; 1.1 mg/kg IV), firocoxib (FIRO;
      0.2 mg/kg PO), and meloxicam (ML; 0.6 mg/kg, IV), on the embryo mobility. Thirty
      mares were divided into three groups (n = 10 per treatment). After the pregnancy
      diagnosis on day 12 after ovulation, the embryo mobility was evaluated by
      transrectal ultrasonography every 5 min for 1 h in order to visualize the
      location of the embryo. In all mares, three evaluations were performed:
      immediately before treatment (pre-treatment), after NSAID administration and 24 h
      after treatment. In group FM, embryo mobility decreased, from 5.8 +/- 0.3
      movements/hour (m/h) to 2.3 +/- 0.5 m/h (p < 0.05) and, after 24 h the values
      were similar to the pre-treatment evaluation (5.9 +/- 0.2 m/h). Likewise, ML
      treatment caused a decrease of embryo movements, from 5.9 +/- 0.3 to 1.9 +/- 0.3
      m/h (p < 0.05), 24 h after treatment values were 5.7 +/- 0.4 m/h. Treatment with
      FIRO did not interfere with embryo mobility (5.7 +/- 0.4; 5.8 +/- 0.3 and 5.6 +/-
      0.3 embryo movements in the first, second and third evaluation, respectively). In
      conclusion, FIRO was the only NSAID that did not alter the embryo mobility and
      may be the safest NSAID for use in early pregnant mares.

PMID- 30300811
TI  - A quantitative morphological analysis of three-dimensional CT coxal bone images
      of contemporary Japanese using homologous models for sex and age estimation.
AB  - Sexual dimorphisms and age-dependent morphological features of the human coxal
      bone were quantitatively analyzed using homologous models created from three
      dimensional (3D) computed tomography images of the pelvis (male: 514 samples,
      female: 388 samples, age 16-100). Bilateral average coxal images of each sex and
      age decade were generated separately through principle component analyses (PCA).
      By measuring average point-to-point distances of 8472 corresponding points
      (average corresponding point differences [ACPDs]) between each homologous coxal
      image and the average images, the sex of more than 93% of the samples was
      correctly assigned. Some principal components (PCs) detected in PCA of the
      homologous models of the samples correlated fairly well with age and are affected
      by features of the curvature of the iliac crest, the arcuate line and the greater
      sciatic notch. Moreover, separate PCA using the average images of each age decade
      successfully detected the first PCs, which were strongly correlated with age.
      However, neither multiple regression analysis using PCs related to age nor
      comparison of ACPDs with the average images of each age decade could produce
      accurate results for age decade assignment of unknown (blind) samples. Therefore,
      more detailed analysis of age-dependent morphological features would be necessary
      for actual age estimation. In addition, some laterality or left and right shape
      difference of the coxal bone images was also elucidated, and was more significant
      in females. Analysis of 3D structures using homologous models and PCA appears to
      be a potential technique to detect subsistent morphological changes of bones.

PMID- 30300812
TI  - Permeability and microstructure of cholesterol-depleted skin lipid membranes and
      human stratum corneum.
AB  - Cholesterol (Chol) is one of the major skin barrier lipids. The physiological
      level of Chol in the stratum corneum (SC) appears to exceed its miscibility with
      other barrier lipids, as some Chol is phase separated. Chol synthesis is
      essential for epidermal homeostasis, yet the role of these Chol domains in SC
      permeability is unknown. We investigated the impact of Chol depletion on the
      permeability properties and microstructure of model membranes and human SC. X-ray
      powder diffraction of membranes constructed from isolated human skin ceramides or
      synthetic ceramides confirmed that only approximately half of the normal Chol
      amount can be incorporated in either long or short periodicity lamellar phases.
      The long periodicity lipid arrangement persisted even in the absence of Chol.
      Infrared spectroscopy suggested that Chol had negligible effects on the lipid
      chain order and packing at physiological skin temperature. Chol depletion of the
      model membranes or isolated human SC did not compromise the barrier function to
      water and two model permeants. On the contrary, the membrane with the Chol
      content reduced to 40% of the normal value, where no separated Chol was observed,
      was significantly less permeable than the control. Thus, a 0.4:1:1 M ratio of
      Chol/ceramides/fatty acids appears sufficient for skin lipids to limit water loss
      and prevent the entry of environmental substances. We speculate that the SC Chol
      domains may have roles in the skin other than barrier function.

PMID- 30300813
TI  - The sensitivity of satellite-based PM2.5 estimates to its inputs: Implications to
      model development in data-poor regions.
AB  - Exposure to fine particulate matter (PM2.5) has been associated with a wide range
      of negative health outcomes. The overwhelming majority of the epidemiological
      studies that helped establish such associations was conducted in regions with
      sufficient ground observations and other supporting data, i.e., the data-rich
      regions. However, air pollution health effects research in the data-poor regions,
      where pollution levels are often the highest, is still very limited due to the
      lack of high-quality exposure estimates. To improve our understanding of the
      desired input datasets for the application of satellite-based PM2.5 exposure
      models in data-poor areas, we applied a Bayesian ensemble model in the southeast
      U.S. that was selected as a representative data-rich region. We designed four
      groups of sensitivity tests to simulate various data-poor scenarios. The factors
      considered that would influence the model performance included the temporal
      sampling frequency of the monitors, the number of ground monitors, the accuracy
      of the chemical transport model simulation of PM2.5 concentrations, and different
      combinations of the additional predictors. While our full model achieved a 10
      fold cross-validated (CV) R2 of 0.82, we found that when reducing the sampling
      frequency from the current 1-in-3 day to 1-in-9 day, the CV R2 decreased to 0.58,
      and the predictions could not capture the daily variations of PM2.5. Half of the
      current stations (i.e., 30 monitors) could still support a robust model with a CV
      R2 of 0.79. With 20 monitors, the CV R2 decreased from 0.71 to 0.55 when 100%
      additional random errors were added to the original CMAQ simulations. However,
      with a sufficient number of ground monitors (e.g., 30 monitors), our Bayesian
      ensemble model had the ability to tolerate CMAQ errors with only a slight
      decrease in CV R2 (from 0.79 to 0.75). With fewer than 15 monitors, our full
      model collapsed and failed to fit any covariates, while the models with only time
      varying variables could still converge even with only five monitors left. A model
      without the land use parameters lacked fine spatial details in the prediction
      maps, but could still capture the daily variability of PM2.5 (CV R2 >= 0.67) and
      might support a study of the acute health effects of PM2.5 exposure.

PMID- 30300814
TI  - Variability of urinary concentrations of non-persistent chemicals in pregnant
      women and school-aged children.
AB  - BACKGROUND: Exposome studies are challenged by exposure misclassification for non
      persistent chemicals, whose temporal variability contributes to bias in dose
      response functions. OBJECTIVES: We evaluated the variability of urinary
      concentrations of 24 non-persistent chemicals: 10 phthalate metabolites, 7
      phenols, 6 organophosphate (OP) pesticide metabolites, and cotinine, between
      weeks from different pregnancy trimesters in pregnant women, and between days and
      between seasons in children. METHODS: 154 pregnant women and 152 children from
      six European countries were enrolled in 2014-2015. Pregnant women provided three
      urine samples over a day (morning, midday, and night), for one week in the 2nd
      and 3rd pregnancy trimesters. Children provided two urines a day (morning and
      night), over two one-week periods, six months apart. We pooled all samples for a
      given subject that were collected within a week. In children, we also made four
      daily pools (combining morning and night voids) during the last four days of the
      first follow-up week. Pools were analyzed for all 24 metabolites of interest. We
      calculated intraclass-correlation coefficients (ICC) and estimated the number of
      pools needed to obtain an ICC above 0.80. RESULTS: All phthalate metabolites and
      phenols were detected in >90% of pools whereas certain OP pesticide metabolites
      and cotinine were detected in <43% of pools. We observed fair (ICC = 0.40-0.59)
      to good (0.60-0.74) between-day reliability of the pools of two samples in
      children for all chemicals. Reliability was poor (<0.40) to fair between
      trimesters in pregnant women and between seasons in children. For most chemicals,
      three daily pools of two urines each (for weekly exposure windows) and four
      weekly pools of 15-20 urines each would be necessary to obtain an ICC above 0.80.
      CONCLUSIONS: This quantification of the variability of biomarker measurements of
      many non-persistent chemicals during several time windows shows that for many of
      these compounds a few dozen samples are required to accurately assess exposure
      over periods encompassing several trimesters or months.

PMID- 30300815
TI  - The association of traffic-related air and noise pollution with maternal blood
      pressure and hypertensive disorders of pregnancy in the HOME study cohort.
AB  - Traffic-related air and noise pollution may increase the risk for cardiovascular
      disorders, especially among susceptible populations like pregnant women. The
      objective of this study was to evaluate the association of exposure to traffic
      related air pollution and traffic noise with blood pressure in pregnant women. We
      extracted systolic blood pressure (SBP) and diastolic blood pressure (DBP) at
      >=20 weeks gestation, as well as hypertensive disorders of pregnancy from medical
      records in the HOME Study, a prospective pregnancy and birth cohort from
      Cincinnati, OH (n = 370). We estimated exposure to elemental carbon attributable
      to traffic (ECAT),1 a marker of traffic-related air pollution, at women's
      residences at ~20 weeks gestation using a validated land use regression model and
      traffic noise using a publicly available transportation noise model. We used
      linear mixed models and modified Poisson regression adjusted for covariates to
      examine associations of ECAT and traffic noise with blood pressure and
      hypertensive disorders of pregnancy risk, respectively. In adjusted models, we
      found a 1.6 (95% CI = 0.02, 3.3; p = 0.048) mm Hg increase in SBP associated with
      an interquartile range increase in ECAT concentration; the association was
      stronger after adjusting for traffic noise (1.9 mm Hg, 95% = 0.1, 3.7; p =
      0.035). ECAT concentrations were not significantly associated with DBP or
      hypertensive disorders of pregnancy, and traffic noise was not associated with
      SBP, DBP, or hypertensive disorders of pregnancy. There was no evidence of a
      joint effect of traffic noise and ECAT on any outcome. In this cohort, higher
      residential traffic-related air pollution exposure at ~20 weeks gestation was
      associated with higher SBP in late pregnancy. It is important for future studies
      of traffic-related air or noise pollution to jointly consider both exposures and
      neighborhood characteristics given their correlation and potential cumulative
      impact on cardiovascular health.

PMID- 30300817
TI  - Natural variability and modulation by environmental stressors of global genomic
      cytosine methylation levels in a freshwater crustacean, Gammarus fossarum.
AB  - To improve the assessment of aquatic organism responses to environmental
      stressors, there is an interest in studying epigenetic marks in addition to other
      validated biomarkers. Indeed, the epigenetic marks may be influenced by the
      surrounding environment. Non-model invertebrates such as gammarids are sentinel
      organisms representative of the diversity of natural stream communities. Despite
      their ecologically relevance, the epigenetic responses have been to date poorly
      documented in these species. The present study explores the measurement of the
      global cytosine methylation level in the genome of the freshwater crustacean
      Gammarus fossarum. In a first step, natural variability of global cytosine
      methylation level (basal level) was assessed by studying the effect of sex, age
      and sampling site of organisms. Results showed a significant effect of age and
      sampling site. In a second step, effects of water temperature and food starvation
      were studied. For both factors, a hypermethylation was observed after 1 month of
      exposure. In a third step, gammarids were exposed to a range of environmentally
      relevant cadmium concentrations (0.05-5 MUg/L) in order to assess the effect of a
      chemical stress. Whatever the cadmium concentration used, a significant
      hypomethylation was observed after 14 days followed by a trend for
      hypermethylation after 1 month of exposure. These results are the first ones
      dealing with the 5C-methylation status in gammarids. The results constitute
      potential markers of environmental stresses in relevant sentinel species widely
      used in ecotoxicological studies.

PMID- 30300816
TI  - Urinary trace metals individually and in mixtures in association with preterm
      birth.
AB  - One in ten infants born in the United States is born preterm, or prior to 37
      weeks gestation. Exposure to elevated levels of metals, such as lead and arsenic,
      has been linked to higher risk of preterm birth (PTB), but consequences of lower
      levels of exposure and less studied metals are unclear. We examined the
      associations between 17 urinary trace metals individually and in mixtures in
      relation to PTB. The LIFECODES birth cohort enrolled pregnant women at <15 weeks
      gestation at Brigham and Women's Hospital in Boston. We selected cases of PTB (n
      = 99) and unmatched controls (n = 291) and analyzed urine samples for a panel of
      trace metals (median: 26 weeks gestation). We used logistic regression models to
      calculate the odds ratio (OR) for PTB and subtypes of PTB based on presentation
      at delivery. Subtypes included spontaneous and placental PTB. We used elastic net
      (ENET) regularization to identify individual metals or pairwise interactions that
      had the strongest associations with PTB, and principal components analysis (PCA)
      to identify classes of exposures associated with the outcome. We observed
      increased odds of PTB (OR: 1.41, 95% Confidence Interval [CI]: 1.12, 1.78) in
      association with an interquartile range difference in urinary copper (Cu). We
      also observed an increased OR for selenium (OR: 1.33, 95% CI: 0.98, 1.81). ENET
      selected Cu as the most important trace metal associated with PTB. PCA identified
      3 principal components (PCs) that roughly reflected exposure to toxic metals,
      essential metals, and metals with seafood as a common source of exposure. PCs
      reflecting essential metals were associated with increased odds of overall and
      spontaneous PTB. Maternal urinary copper in the third trimester was associated
      with increased risk of PTB, and statistical analyses for mixtures indicated that
      after accounting for correlation this metal was the most important statistical
      predictor of the outcome.

PMID- 30300818
TI  - Women with compulsive buying or gambling disorder: Similar profiles for different
      behavioural addictions.
AB  - The aim of the present study was to examine the differences in sociodemographic
      and clinical characteristics of 104 women diagnosed with compulsive buying
      behaviour (CBB = 55) or gambling disorder (GD = 49) treated at three public
      hospitals unit specialized in behavioural addictions from January 2004 to
      December 2015. Significant between-group differences in sociodemographic
      variables were observed for cohabitation status (living with a partner or not)
      and educational level, with a higher percentage of women in the GD group
      cohabiting (x2 (1), p = .029). By contrast, the CBB group had a significantly
      higher educational level (x2 (1) = 7.4, p = .007). There were no significant
      differences between the groups in age of onset, age at treatment initiation, age
      at the onset of behavioural problems, or in the years elapsed until presenting
      addiction problems. However, there were significant between-group differences in
      the amount of money spent weekly (F (1.100) = 4.9, p = .028), with women in the
      CBB group spending on average ?289.4/week (SD, 412.4) versus ?151/week (SD,
      141.23) in the GD group. The CBB group had significantly more depressive
      disorders compared to the GD group (x2(1) = 5.4, p = .020). In contrast, the GD
      group presented significantly more tobacco use than the CBB group (x2(1) = 1.19,
      p = .000). This study suggests that women with CBB or GD share more
      characteristics than differences and the treatment approaches must take into
      account gender related factors.

PMID- 30300819
TI  - Spinal cord infarction with ipsilateral segmental neuropathic pain and flaccid
      paralysis. A functional role for human afferent ventral root small sensory
      fibres.
AB  - This paper illustrates the cases of two patients with an acute onset of right
      brachial neuropathic pain, flaccid paralysis and contralateral thermal and
      thermal pain hypoesthesia, without posterior column impairment nor pyramidal
      signs below the segmental lesion. MRI showed right sided spinal cord infarction,
      in the anterior spinal artery territory between C1 and C5 in one patient and
      between C3 and C7 in the other. Contact Heat Evoked Potentials and Quantitative
      Thermal Sensory testing are consistent with contralateral, but not ipsilateral,
      spinothalamic tract involvement. Electromyographic results established
      ipsilateral segmental denervation and somatosensory evoked responses were
      consistent with dorsal column sparing. Unilateral anterior cervical spinal cord
      infarction may present with acute ipsilateral segmental neuropathic pain, lower
      motor neurone-type weakness, contralateral thermoanalgesia and no pyramidal
      signs. The ipsilateral pain provides novel evidence that in some instances,
      ventral roots can play a role in nociception in humans. The infarcted territory
      may result from occlusion of a sulcal commissural artery or a number of more
      proximal vessels (including a single or duplicated anterior spinal artery,
      vertebral arteries or feeding radicular arteries).

PMID- 30300820
TI  - 360 degrees  multiparametric imaging atomic force microscopy: A method for three
      dimensional nanomechanical mapping.
AB  - Atomic Force Microscopy (AFM) has been intensively used for imaging,
      characterization and manipulation at the micro- and nanoscale. Taking into
      account that the material is usually anisotropic, it needs to be characterized in
      various regions and orientations. Although recent advances of AFM techniques have
      allowed for large area scan of the sample on a two-dimensional plane, mapping a
      three-dimensional (3D) sample at a full orientation of 360 degrees  remains
      challenge. This paper reports a multiparametric imaging atomic force microscope
      via robot technique for 360 degrees  mapping and 3D reconstruction of the
      sample's topography and nanomechanical properties. The system is developed by
      integrating a three degrees of freedom (DoFs) high-precision rotation stage and a
      home positioning approach is proposed to compensate for the eccentric distance
      between the cross-section center of the sample and the ration center of the
      stage. With this method, the sample surface can be fully mapped by the force
      distance-based AFM via rotating the sample with a complete orientation. 360
      degrees  multiparametric mapping and 3D reconstruction results (e.g., topography,
      adhesion, modulus, energy dissipation) of a human hair demonstrate practicability
      and reliability of the proposed method.

PMID- 30300821
TI  - NF-kappaB signaling activation via increases in BRD2 and BRD4 confers resistance
      to the bromodomain inhibitor I-BET151 in U937 cells.
AB  - Novel epigenetic therapies targeting bromodomain and extra-terminal (BET) family
      proteins have shown therapeutic efficacy in diverse hematologic malignancies and
      solid cancers. However, the mechanism of resistance remains poorly understood. In
      the present study, we evaluated the mechanism of resistance to the BET inhibitor
      I-BET151 and its signaling pathway to overcome resistance in U937 cells.
      Treatment with 10 MUM I-BET151 significantly induced growth inhibition,
      apoptosis, and cell cycle modulation, including increases in sub-G1 and G1 phases
      and decreases in S and G2/M phases, in U937 cells. However, no significant
      changes in these factors were detected in I-BET151-resistant U937 (U937R) cells.
      Combined treatment with I-BET151 and IKK inhibitor VII synergistically induced
      apoptosis in U937 and U937R cells. Increased expression of bromodomain-containing
      protein (BRD) 2, BRD4, and nuclear NF-kappaBp65 proteins was detected in U937R
      cells. IKK inhibitor VII inhibited the activation of NF-kappaBp65 protein in the
      nuclear fraction of U937R cells. These findings suggest that resistance to I
      BET151 in U937R cells is related to constitutive activation of the NF-kappaB
      signaling pathway via increased expression of both BRD2 and BRD4. Targeting the
      NF-kappaB signaling pathway may be an effective therapeutic strategy to enhance
      or restore the sensitivity to I-BET151 in U937 cells.

PMID- 30300822
TI  - Outcomes of fludarabine, high dose cytarabine and granulocyte-colony stimulating
      factor (FLAG) as re-induction for residual acute myeloid leukemia on day 14 bone
      marrow.
AB  - BACKGROUND: Patients with acute myeloid leukemia (AML) treated with intensive
      chemotherapy may require re-induction based on the evaluation of day 14 bone
      marrow biopsy. METHODS: A retrospective chart review was performed to evaluate
      adult patients with AML who received re-induction with fludarabine, high dose
      cytarabine and granulocyte colony stimulating factor (FLAG) regimen for residual
      disease (>= 5% blasts by morphology) on day 14 bone marrow examination between
      September 2012 and July 2017 at our institution. RESULTS: We identified 27
      patients who received FLAG therapy for treatment of residual disease on day 14
      marrow examination following initial induction. The median age at diagnosis was
      61 years and the majority of patients had poor risk AML. The overall response
      rate was 78% and 15 patients proceeded to allogeneic hematopoietic stem cell
      transplantation. CONCLUSION: The regimen was well tolerated and is a viable re
      induction option for patients with residual disease on a day 14 bone marrow.

PMID- 30300823
TI  - An mTORC1/2 kinase inhibitor enhances the cytotoxicity of gemtuzumab ozogamicin
      by activation of lysosomal function.
AB  - Gemtuzumab ozogamicin (GO), the first antibody-drug conjugate (ADC), has
      attracted the interest of hematologists because more than 90% of acute myeloid
      leukemia (AML) blasts express its target, CD33. Although GO and subsequently
      developed ADCs depend on lysosomes for activation, lysosome number and activity
      in tumor cells has not been well elucidated. In this study, we investigated
      whether an mTORC1/2 kinase inhibitor, PP242, which was reported to activate
      lysosomal function, potentiates the cytotoxicity of GO in AML cells. Eight AML
      cell lines (U937, THP-1, SKM-1, SKK-1, SKNO-1, HL-60, MARIMO and KO52) were
      treated with GO and PP242. The cytotoxic effect of GO was enhanced by concurrent
      treatment with a non-cytotoxic concentration (500 nM) of PP242 in most cell
      lines, except MARIMO and KO52 cells. We then used LysoTracker to label acidic
      lysosomes in U937, THP-1, SKM-1, MARIMO and KO52 cells. LysoTracker fluorescence
      was dramatically increased by treatment with PP242 in U937, THP-1 and SKM-1
      cells, and the intensified fluorescence was retained with PP242 + GO. In
      contrast, PP242 did not induce a significant increase in fluorescence in MARIMO
      cells, consistent with the lack of combinatory cytotoxicity. LysoTracker
      fluorescence was also increased by PP242 in KO52 cells, which have been reported
      to strongly express multidrug resistance (MDR). Further, PP242 suppressed GO
      induced Chk1 activation and G2/M cell cycle arrest, which in turn triggered cell
      cycle promotion and cell death. These results indicate that inhibition of
      mTORC1/2 kinase by PP242 enhanced the cytotoxicity of GO by increasing lysosomal
      compartments and promoting the cell cycle via suppression of GO-induced Chk1
      activation. This combination may represent an attractive new therapeutic strategy
      for the treatment of leukemia.

PMID- 30300824
TI  - Hole free phase plate tomography for materials sciences samples.
AB  - We report, for the first time, the three dimensional reconstruction (3D) of a
      transistor from a microprocessor chip and roughness of molecular electronic
      junction obtained by electron tomography with Hole Free Phase Plate (HFPP)
      imaging. The HFPP appears to enhance contrast between inorganic materials and
      also increase the visibility of interfaces between different materials. We
      demonstrate that the degree of enhancement varies depending on material and
      thickness of the samples using experimental and simulation data.

PMID- 30300825
TI  - Ion transmission through a dielectric hollow tip for scanning probe microscopy.
AB  - We present a new concept for scanning probe microscopy characterization of
      molecular microstructures. It is based on a thin capillary using as a sharp tip
      to probe and map the morphology of a surface. In our experiment a collimated ion
      beam is formed by tungsten ions passing through a quartz tapered capillary with a
      100-nm aperture and enters a 2D position-sensitive detector. We demonstrate that
      such ions are capable of producing the image of a dielectric nanoaperture in the
      case of low-dose ion beam. Ion transmission through a nanoscale capillary opens
      the door to observing photodesorption of large organic molecular ions with high
      spatially-element resolution using the combination of a hollow-tip vacuum scanner
      with time-of-flight mass spectrometer.

PMID- 30300826
TI  - Altered spatial and temporal concordance among intrinsic brain activity measures
      in schizophrenia.
AB  - Various data-driven voxel-wise measures derived from resting-state functional
      magnetic resonance imaging (rs-fMRI) have been developed to characterize
      spontaneous brain activity. These measures have been widely applied to explore
      brain functional changes in schizophrenia and have enjoyed significant success in
      unraveling the neural mechanisms of this disorder. However, their spatial and
      temporal coupling alterations in schizophrenia remain largely unknown. To address
      this issue, 88 schizophrenia patients and 116 gender- and age-matched healthy
      controls underwent rs-fMRI examinations. Kendall's W was used to calculate volume
      wise (across voxels) and voxel-wise (across time windows) concordance among
      multiple commonly used measures, including fractional amplitude of low frequency
      fluctuations, regional homogeneity, voxel-mirrored homotopic connectivity, degree
      centrality and global signal connectivity. Inter-group differences in the
      concordance were investigated. Results revealed that whole gray matter volume
      wise concordance was reduced in schizophrenia patients relative to healthy
      controls. Although two groups showed similar spatial distributions of the voxel
      wise concordance, quantitative comparison analysis revealed that schizophrenia
      patients exhibited decreased voxel-wise concordance in gray matter areas spanning
      the bilateral frontal, parietal, occipital, temporal and insular cortices. In
      addition, these concordance changes were negatively correlated with onset age in
      schizophrenia patients. Our findings suggest that the concordance approaches may
      provide new insights into the neural mechanisms of schizophrenia and have the
      potential to be extended to neuropsychiatric disorders.

PMID- 30300828
TI  - Potentiality of microemulsion systems in treatment of ophthalmic disorders:
      Keratoconus and dry eye syndrome - In vivo study.
AB  - Microemulsions are widely studied as potential ocular drug delivery vehicles. In
      the present study we show the versatility of possible use microemulsions as
      ocular delivery vehicle. The ME is loaded with a hydrophilic drug, riboflavin
      phosphate (RFP) and a lipophilic, docosahexaenoic acid in triglyceride form (TG
      DHA), each separately. These drugs treat keratoconus and dry eye syndrome,
      respectively. The advantage of using ME loaded with RFP is in overcoming eye
      epithelium debridement during collagen cross-linking therapy for treatment of
      keratoconus. ME loaded with lipophilic TG-DHA provides convenient dosage in
      liquid aqueous form of administration of highly lipophilic TG-DHA, which is known
      as a protective molecule in dry eye syndrome. The capability of RFP-loaded MEs
      was demonstrated in terms of improvement of biomechanical strength of the rabbit
      cornea, as a result of successful penetration of RFP through the intact
      epithelium. TG-DHA-loaded microemulsion applied topically onto an eye with
      induced dry eye syndrome showed the significant relief of the dry eye condition.

PMID- 30300827
TI  - Expression of the Immune Checkpoint Modulator OX40 in Acute Lymphoblastic
      Leukemia Is Associated with BCR-ABL Positivity.
AB  - OX40 and its ligand are members of the TNF/TNF receptor superfamily, which
      includes various molecules influencing cellular signaling and function of both
      tumor and immune cells. The ability of OX40 to promote proliferation and
      differentiation of activated T cells fueled present attempts to modulate this
      immune checkpoint to reinforce antitumor immunity. While we recently found
      evidence for the involvement of OX40 in pathophysiology of acute myeloid leukemia
      including natural killer (NK) cell immunosurveillance, less is known on its role
      in acute lymphoblastic leukemia (ALL). In the present study, OX40 expression on
      ALL cells was significantly associated with positivity for the adverse risk
      factor BCR-ABL. In line, signaling via OX40 increased metabolic activity of
      primary ALL cells and resulted in release of cytokines involved in disease
      pathophysiology. Furthermore, interaction of ALL-expressed OX40 with its cognate
      ligand on NK cells stimulated ALL cell lysis. The data presented thus not only
      identify the yet unknown involvement of OX40/OX40L in ALL pathophysiology and NK
      cell immunosurveillance but also point to the necessity to thoroughly consider
      the consequences of modulating the OX40/OX40L molecule system beyond its effects
      on T cells when developing OX40-targeting approaches for cancer immunotherapy.

PMID- 30300829
TI  - Entrapment and growth of Chlamydomonas reinhardtii in biocompatible silica
      hydrogels.
AB  - In this work, we aimed at improved viability and growth of the microalga
      Chlamydomonas reinhardtii in transparent silica hydrogels based on low-ethanol,
      low-sodium and low-propylamine synthesis. Investigation into replacement of
      conventional base KOH by buffers dipotassium phosphate and
      tris(hydroxymethyl)aminomethane along with increased precursor concentrations
      yielded an aqueous synthesis route which provided a gelation within 10 min,
      absorptions below 0.1 and elastic moduli of 0.04-4.23 kPa. The abrasion
      resistance enhanced by 41% compared to calcium alginate hydrogels and increased
      to 70-85% residual material on addition of chitosan. Entrapment of microalgae in
      low-sodium and low-propylamine silica hydrogels maintained the PSII quantum yield
      above 0.3 and growth rates of 0.23 +/- 0.01 d-1, similarly to cells entrapped in
      calcium alginate. These promising results pave the way for the entrapment of
      sensitive, photosynthetically active and growing cells for in robust
      biotechnological applications.

PMID- 30300830
TI  - Preparation of antimicrobial gold and silver nanoparticles from tea leaf
      extracts.
AB  - Gold and silver nanoparticles were prepared from the green tea and black tea
      extracts of the leaves of Camellia sinensis. The metal nanoparticle solutions
      were obtained by reacting HAuCl4 or AgNO3 aqueous solutions with aqueous NaHCO3
      and tea leaf extracts, which were obtained from used tea leaves at low
      temperature, under ambient conditions. The nanoparticles were stable at room
      temperature and had a uniform particle size (Au: ~10 nm, Ag: ~30 nm).
      Nanoparticle-immobilized cotton cloths were then prepared, which displayed high
      antibacterial activity and a characteristic color, thereby showing potential
      application as antimicrobial pigments. This study provides a means of utilizing
      used tea leaves, which would otherwise be considered waste products.

PMID- 30300831
TI  - Synthesis of ultra-small Rh nanoparticles congregated over DNA for catalysis and
      SERS applications.
AB  - Exploration of rare earth metals for the Surface Enhanced Raman Scattering (SERS)
      is greatly preferred to identify probe molecules even at nano molar level. Highly
      stable Rh nanoparticles (NPs) which are ultra-small size have been prepared
      within 20 min of reaction time as a colloidal solution using a bio-molecular
      scaffold DNA and NaBH4 as a reducing agent under room temperature. While keeping
      metal ion concentration fixed and by making difference in DNA concentration,
      three different sets of Rh@DNA such as 0.08, 0.085 and 0.09 M were formed as
      nanochains like structure with varying diameters. The average chain length of Rh
      NPs for varying concentrations of DNA is ~98 nm and the Rh particles size is
      below 5 nm in all the cases. These ultra-small Rh NPs have been utilized for two
      distinct potential applications such as in catalysis and SERS studies. From the
      catalysis reaction, reduction of 4-Nitro benzaldehyde to 4-amino benzaldehyde,
      Rh@DNA (0.08 M) has shown rate constant value of 0.26 min-1 which is highest
      among other concentrations studied. SERS study revealed that the calculated
      Enhancement Factor (EF) value was 1.19 * 105 for Rh@DNA (0.08 M) which is highest
      while compared with other concentrations. Apart from catalysis and SERS, the as
      synthesized Rh NPs can find applications in other interdisciplinary fields such
      as organic catalysis, electro-catalysis and so on in near future.

PMID- 30300832
TI  - Poly(d,l-lactic-co-glycolic acid) (PLGA) hollow fiber with segmental
      switchability of its chains sensitive to NIR light for synergistic cancer
      therapy.
AB  - This work introduces a new fibrous system for synergistic cancer therapy. The
      system consists of poly(d,l-lactic-co-glycolic acid) (PLGA) fibers with a core
      encapsulating an anticancer drug and a shell entrapping gold nanorods (AuNRs) as
      a photothermal agent. On exposure to NIR light, the photothermal agent generates
      heat to raise the local temperature of the fibers. If the temperature is above a
      glass transition (Tg) of the polymer, the polymer chains will be mobile,
      increasing free volume in size within the shell. As a result, a rapid release of
      the drug can be achieved. When NIR light is turned off, the release will stop
      with inactivity of the photothermal agent, followed by freezing the segmental
      motion of the polymer chains. The on-off switching of NIR light in a time
      controllable manner allows a repeated and accurate release of the drug, leading
      to the significant enhancement of anticancer activity in combination with the
      hyperthermia effect arising from the photothermal agent.

PMID- 30300833
TI  - Biocompatible graphene-based nanoagent with NIR and magnetism dual-responses for
      effective bacterial killing and removal.
AB  - Antibiotics have been widely used in clinical applications to treat pathogenic
      infections at present, but the problem of drug-resistance associated with the
      abuse of antibiotics has become a large threat to human beings. Herein, we
      developed an antibacterial nanoagent by coating quaternized chitosan (QCS) on the
      surface of Fe3O4 nanoparticles-anchored graphene oxide (GO), which enabled QCS
      and GO to achieve synergistic effects on killing the drug-resistant bacteria.
      Systematical antibacterial experiments showed that the prepared nanoagent had
      antibacterial ability, which was significantly enhanced after the introduction of
      near-infrared (NIR). Importantly, the nanoagent could be easily recycled and
      reused without the reduction of the antibacterial ability. During the test time,
      this nanoagent exhibited no obviously toxic side effect to cells. Given the above
      advantages, we anticipate that the nanoagent has a promising future in various
      applications such as wound disinfection, water purification, and surface
      sterilization of medical devices.

PMID- 30300834
TI  - An investigation into the release behavior of solid lipid microparticles in
      different simulated gastrointestinal fluids.
AB  - In recent years there has been a growing interest in solid lipid-based systems,
      particularly in solid lipid microparticles (SLMs); however, only very few studies
      deeply investigated the dissolution behaviour of orally delivered-SLMs. The
      present study provides new insights about the release performance in different
      gastrointestinal fluids of SLMs containing a freely water soluble drug (caffeine,
      as BCS class I drug). Three different formulations of SLMs were prepared by spray
      congealing using lipid excipients belonging to three chemical classes: fatty
      acids, triglycerides and waxes. The dissolution profiles of caffeine were
      investigated using various updated biorelevant dissolution media simulating the
      conditions of the gastrointestinal tract (gastric tract and proximal human
      intestine). The profiles were statistically compared and the morphological
      changes of the particles after dissolution were assessed by SEM analysis. The
      influence of the SLMs composition resulted to be crucial on the dissolution
      behavior in the case of bigger particles (>250 MUm), while smaller SLMs (100-250
      MUm) were mainly affected by the fluid composition. Moreover, regardless of the
      particle size, greater differences in drug release profiles were noted by using
      different intestinal media compared to those obtained in gastric media. In
      particular, the drug release from fatty acid and triglyceride-based SLMs was more
      controlled in the phosphate buffer than in the intestinal biorelevant media;
      while the opposite behavior was noticed for waxy-bases SLMs. Overall, the present
      study provides interesting insights which can be useful for the design of a
      multiparticulated solid lipid formulation.

PMID- 30300835
TI  - Long-term exposure to high-sucrose diet down-regulates hepatic endoplasmic
      reticulum-stress adaptive pathways and potentiates de novo lipogenesis in weaned
      male mice.
AB  - Childhood consumption of added sugars, such as sucrose, has been associated to
      increased risk of metabolic syndrome (MetS) and nonalcoholic fatty liver disease
      (NAFLD). Although the mechanisms underlying NAFLD onset are incompletely defined,
      recent evidence has proposed a role for the endoplasmic reticulum (ER) stress.
      Thus, the present study sought to investigate the metabolic outcomes of high
      sucrose intake on weaned Swiss mice fed a 25% sucrose diet for 30, 60 and 90 days
      in comparison to regular chow-fed controls. High-sucrose feeding promoted
      progressive metabolic and oxidative disturbances, starting from fasting and fed
      hyperglycemia, hyperinsulinemia, glucose intolerance and increased adiposity at
      30-days; passing by insulin resistance, hypertriglyceridemia and NAFLD onset at
      60 days; until late hepatic oxidative damage at 90 days. In parallel, assessment
      of transcriptional and/or translational levels of de novo lipogenesis (DNL) and
      ER stress markers showed up-regulation of both fatty acid synthesis (ChREBP and
      SCD1) and oxidation (PPARalpha and CPT-1alpha), as well as overexpression of
      unfolded protein response sensors (IRE1alpha, PERK and ATF6), chaperones (GRP78
      and PDIA1) and antioxidant defense (NRF2) genes at 30 days. At 60 days, fatty
      acid oxidation genes were down-regulated, and ER stress switched over toward a
      proapoptotic pattern via up-regulation of BAK protein and CHOP gene levels.
      Finally, down-regulation of both NRF2 and CPT-1alpha protein levels led to late
      up-regulation of SREBP-1c and exponential raise of fatty acids synthesis. In
      conclusion, our study originally demonstrates a temporal relationship between DNL
      and ER stress pathways toward MetS and NAFLD development on weaned rats fed a
      high-sucrose diet.

PMID- 30300836
TI  - Bio-accessible milk casein derived tripeptide (LLY) mediates overlapping anti-
      inflammatory and anti-oxidative effects under cellular (Caco-2) and in vivo
      milieu.
AB  - Inflammation and oxidative stress are closely linked patho-physiological
      processes which occur concurrently in many diseased conditions. Recently,
      interdependence between these two processes explains the antioxidant paradox
      associated with failure to select appropriate agents required for prevention of
      diseases known to be induced by oxidative stress. Present study established the
      overlapping anti-inflammatory and anti-oxidative potential along with bio
      accessibility of milk casein derived tripeptide (LLY). Tripeptide exhibited anti
      inflammatory response under ex vivo conditions by suppressing (P<.01) mice
      splenocytes proliferation and modulating their cytokines (IFN-gamma, IL-10 and
      TGF-beta) with improved phagocytosis of peritoneal macrophages. Conversely,
      tripeptide displayed extraordinary radical scavenging ability and cellular anti
      oxidative potential using chemical assays and H2O2 induced oxidative stress model
      on Caco-2 cells. Under cellular assessment, on one hand tripeptide inhibited
      (P<.01) intracellular ROS generation and reduced MDA and protein carbonyls but on
      the other also increased (P<.01) the activity of anti-oxidative enzyme, catalase
      without much effect on SOD and GPx. This anti-oxidative potential was further
      established by studying relative expression of genes (Nrf-2 and Keap1) and Nrf-2
      nuclear translocation associated with anti-oxidative signaling in Caco-2 cells.
      Bio-accessibility of tripeptide and its intact transport across Caco-2 cell
      monolayer was also found to be 1.72+/-0.22% through PepT1 mediated transport
      mechanism. Besides, tripeptide displayed strong anti-oxidative and anti
      inflammatory potential under in vivo conditions in mice against ethanol induced
      oxidative stress by elevating (P<.01) liver GSH content and by decreasing (P<.01)
      the activities of anti-oxidative enzymes, MDA along with reduced expression of
      CYP2E1, PPAR-alpha, TNF-alpha and COX-2 genes than ethanol control.

PMID- 30300837
TI  - Obesity alters the uterine environment before pregnancy.
AB  - Obesity is a metabolic disorder that predisposes to numerous diseases and has
      become a major global public health concern. Cafeteria diet (CAF) is the animal
      model used for the study of obesity that more closely reflects Western diet
      habits. Previously, we described that CAF administration for 60 days induces
      obesity in female rats and their fetuses develop macrosomia. Given that, in our
      model, rats are not genetically modified and that obese mothers were fed standard
      chow during pregnancy, the aim of the current study was to test the hypothesis
      that obesity alters the intrauterine environment prior to pregnancy, and this may
      explain the exacerbated fetal weight gain. We found that uteri from obese rats
      during the estrous phase developed insulin resistance through mechanisms that
      involve the induction of uterine hypoxia and the down-regulation of the insulin
      receptor gene. Moreover, uterine cell proliferation was induced by obesity
      concomitantly with the reduction in the uterine contractile response to a beta2
      AR agonist, salbutamol, and this may be consequence of the down-regulation in the
      uterine beta2 AR expression. We conclude that CAF-induced obesity alters the
      uterine environment in rats during the estrous phase and may cause the fetal
      macrosomia previously described by us in obese animals. The lower sensitivity of
      the uterus to a relaxation stimulus (salbutamol) is not a minor fact given that
      for implantation to occur the uterus must be relaxed for embryo nidation. Thus,
      the alteration in the uterine quiescence may impair implantation and,
      consequently, the foregoing pregnancy.

PMID- 30300838
TI  - Cancer epidemiology fieldwork in a resource-limited setting: Experience from the
      western Kenya ESCCAPE esophageal cancer case-control pilot study.
AB  - BACKGROUND: Case-control studies remain an important study design for aetiologic
      research on cancer, particularly when cohorts are not available. In addition to
      the potential biases inherent in this design, conducting fieldwork in settings
      with weak health care and information systems for cancer, such as in sub Saharan
      Africa, confer additional challenges which we present here with the aim to share
      experience to guide future studies. METHODS: We undertook a hospital-based case
      control study of squamous cell esophageal cancer at the Moi Teaching and Referral
      Hospital in Eldoret, West Kenya. Cases were recruited at endoscopy and controls
      from hospital wards, age and gender frequency-matched to cases. Urine, toenails,
      blood and tumour biopsy were collected and a questionnaire administered. RESULTS:
      During this pilot phase, 143 cases and 155 controls were successfully recruited.
      Complete questionnaire data was obtained through e-data collection. Biospecimen
      collection was possible with support of an already existing equipped laboratory.
      We introduce changes made in the main study phase, including on expansion of the
      control groups to allow to consideration of selection bias. CONCLUSIONS: Extra
      attention and funding to train and monitor data quality and biospecimen
      collection and collaboration of a large group held together by strong leadership
      are essential. We recommend studies based on regional treatment centres with
      their more defined catchment areas rather than in the capital cities as referral
      routes in multi-level health care systems are severely attrition prone.

PMID- 30300839
TI  - Modulation of heat-shock response is associated with Di (2-ethylhexyl) phthalate
      (DEHP)-induced cardiotoxicity in quail (Coturnix japonica).
AB  - Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant with
      endocrine disrupting properties. As a plasticizer, DEHP can be leach from the
      plastic to transfer the external environment and thus enters the animal food
      chain, causing serious damage to the animal organs. The heat-shock response (HSR)
      comprising heat-shock protein (HSPs) and heat-shock transcription factor (HSFs)
      plays a pivotal role in various toxic stress conditions. For the sake of
      investigating the effects of DEHP exposure on cardiac toxicity and the regulation
      of HSR, male quail were fed the diet with 0, 250, 500 and 750 mg/kg DEHP by
      gavage administration for 45 days. Histopathological changes including
      cardiomyocyte swelling and muscle fiber dilatation were observed in the hearts
      exposed to DEHP. During the DEHP treatment, the mRNA expression of HSP60 and
      HSP70 were universally reduced, while the expression of other HSPs (HSP10, HSP25,
      HSP27, HSP40, HSP47, HSP90, HSP110) had different degrees of growth. In addition,
      the levels of HSF1, HSF2, and HSF3 were significantly increased. Given the facts
      above, DEHP exposure induced the toxic effects of quail heart. DEHP exposure did
      great harm to HSR via affecting the synthesis of HSFs to mediate the
      transcription of the HSPs. Ultimately, this study provided new evidence that DEHP
      induced cardiotoxicity in quail was related to activation of HSR and playing a
      protective role.

PMID- 30300840
TI  - Adsorption of phenolic compounds from water by a novel ethylenediamine rosin
      based resin: Interaction models and adsorption mechanisms.
AB  - This study describes the adsorption performance of a novel ethylenediamine rosin
      based resin (EDAR) for several industrially-important phenolic compounds. Its
      removal of 4-nitrophenol (4-NP) from water was comparable to or better than many
      commercial resins, although it was less effective with other phenols (i. e.,
      phenol, 2,4-dichlorophenol, 4-chlorophenol, and 4-methylphenol). Experimental
      conditions for batch adsorption of 4-NP by EDAR are evaluated, the adsorption
      kinetics is well described by the pseudo-second-order model (R2 > 0.99) and
      isotherm follows the Langmuir isotherm model (R2 > 0.99), with the maximum
      monolayer adsorption capacity of 82 mg g-1 at pH 6.0 and 293 K. The thermodynamic
      parameters indicate that the adsorption is spontaneous and endothermic. Also,
      quantum chemistry calculations indicate involvement of hydrogen-bonding between 4
      NP and amino groups of EDAR. 4-NP was efficiently desorbed from the loaded EDAR
      resin by 0.2 M HCl, and the resin could be recycled with only a small decrease in
      its initial adsorption capacities. Thus, EDAR is a promising adsorbent for the
      removal of 4-NP during water treatment.

PMID- 30300841
TI  - Harmful effect of nanoparticles on the functions of freshwater ecosystems:
      Insight into nanoZnO-polluted stream.
AB  - ZnO nanoparticle toxicity on aquatic organisms has been extensively studied, but
      its concentration-and time-dependent effects on ecosystem functioning are remain
      uncertain. Here we assessed the harmful effects of nano-ZnO (10, 100, 1000 mg L
      1) on the stream functioning by using a microcosm system simulating poplar leaf
      decomposition for 50 days. The 100 mg L-1 ZnO nanoparticles had significantly and
      stably inhibitory effect on the litter decomposition during the exposure period.
      The inhibition was not detected in the 10 mg L-1 treatment until 43 d. In
      contrast, the significant and continuous inhibition started to disappear from 43
      d in the 1000 mg L-1 treatment. The varied consequences on litter decomposition
      might be directly affected by the different ZnO nanoparticle homogeneity of the
      different treatments. ZnO nanoparticles led to significant decreases in pH value
      of the decomposition environment, which had significant and positive
      relationships to the activities of dehydrogenase, glycine-aminopeptidase, N
      acetylglucosaminidase, and acid phosphatase. Besides, 10 and 1000 mg L-1 ZnO
      nanoparticles led to lower fungal diversity, which was negatively related to the
      variability of decomposition. In conclusion, fungal decomposers showed different
      responses to the different concentrations of ZnO nanoparticle, and ultimately
      affected the stability of ecosystem functions.

PMID- 30300842
TI  - Does early object exploration support gesture and language development in
      extremely preterm infants and full-term infants?
AB  - BACKGROUND: An increasing body of research on typically and atypically developing
      infants has shown that motor skills play an important role in language
      development. To date, however, the role of specific object exploration skills for
      early gesture and vocabulary development has not been investigated in extremely
      low gestational age infants (ELGA, GA < 28 weeks), who are at greater risk for
      motor and language delays than full-term (FT) infants. PURPOSE: This longitudinal
      study examined relations between 6-month active exploratory behaviors and 12-
      month word comprehension, gestures and vocal production, controlling for
      cognitive performance and neonatal condition (ELGA vs FT). METHODS: Forty
      infants, 20 ELGA and 20 FT, and their mothers participated in the study. Mother
      infant play interaction was video-recorded at 6 and 12 months. Oral and manual
      object exploration at 6 months and spontaneous gestures and vocal production at
      12 months were coded. Word comprehension was evaluated with the Italian version
      of the MacArthur-Bates CDI parent questionnaire at 12 months. Cognitive
      performance was examined with the Griffiths Mental Developmental Scales at 6
      months and the Bayley-III Scales at 12 months. RESULTS: Regression analyses
      showed that after accounting for cognitive performance and neonatal condition,
      oral exploration was related to word comprehension, and manual exploration to
      gestures and vocal production in the overall sample. CONCLUSIONS: Cascading
      effects of specific object exploration skills on gestures and language
      comprehension and production in preterm infants and FT infants are discussed.
      Clinical implications for early assessment of and interventions involving object
      exploration skills, which may affect language development, are considered for the
      preterm population.

PMID- 30300843
TI  - Structural exploration of cinnamate-based phosphonic acids as inhibitors of
      bacterial ureases.
AB  - The conjugated system of cinnamic acid, alpha-substituted with a phosphonoalkyl
      residue, was previously validated as a scaffold that provided one of the most
      potent organophosphorus inhibitors of bacterial urease. Following the idea of
      using Morita-Baylis-Hillman adducts to introduce the terminal phosphonic side
      chain functionality to the alpha,beta-unsaturated system, we currently report the
      synthesis and activity of an extended series of compounds. Cinnamates modified
      with 3-phosphonopropyl and 4-phosphonobutyl side chains were obtained in a
      convenient two-step procedure, which involved Pd-mediated transformations of the
      Morita-Baylis-Hillman bromides as the key substrates. The introduction of a
      terminal alkenyl fragment, which was achieved by Stille coupling with stannanes,
      was followed by a tandem C-P bond formation/oxidation process. A submicromolar
      ligand of Sporosarcina pasteurii urease (Ki = 0.509 MUM) was identified among the
      active molecules. In addition, inhibitors of Proteus mirabilis urease affected
      bacterial growth at the micromolar level. Based on the structure-activity
      relationship and the mechanism of inhibition, we suggest a nontypical mixed mode
      of action for the slow binding compounds. We presume that the molecular distance
      between the phosphonic group and the backbone double bond allows a dual activity:
      complexation of the acidic group with nickel ions and Michael addition of a
      cysteine forming the active site lid.

PMID- 30300844
TI  - Designing dichlorobinaphthoquinone as a prooxidative anticancer agent based on
      hydrogen peroxide-responsive in situ production of hydroxyl radicals.
AB  - Compared with normal cells, cancer cells harbor increased levels of reactive
      oxygen species (ROS) including hydrogen peroxide (H2O2), and therefore are more
      vulnerable to further ROS production. This biochemical difference favors the idea
      of developing new powerful selective prooxidative anticancer agents. However, it
      still remains a challenge to design them by targeting this difference. Herein, we
      report the designed dichlorobinaphthoquinone as a prooxidative anticancer agent
      which is capable of exploiting increased levels of H2O2 of cancer cells to
      produce in situ lethal hydroxyl radicals (HO*) and thereby kill them selectively,
      a design strategy inspired from Zhu et al.'s work on the molecular mechanism for
      metal-independent production of HO*.

PMID- 30300845
TI  - 1-(2-Hydroxybenzoyl)-thiosemicarbazides are promising antimicrobial agents
      targeting d-alanine-d-alanine ligase in bacterio.
AB  - The bacterial cell wall and the enzymes involved in peptidoglycan synthesis are
      privileged targets for the development of novel antibacterial agents. In this
      work, a series of 1-(2-hydroxybenzoyl)-thiosemicarbazides inhibitors of D-Ala-D
      Ala ligase (Ddl) were designed and synthesized in order to target resistant
      strains of bacteria. Among these, the 4-(3,4-dichlorophenyl)-1-(2-hydroxybenzoyl)
      3-thiosemicarbazide 29 was identified as a potent Ddl inhibitor with activity in
      the micromolar range. This compound, possessing strong antimicrobial activity
      including against multidrug resistant strains, was proven to act through a
      bactericidal mechanism and demonstrated very low cytotoxicity on THP-1 human
      monocytic cell line. Inhibition of Ddl activity by 29 was confirmed in bacterio
      using UPLC-MS/MS by demonstrating an increase in D-Ala intracellular pools
      accompanied by a commensurate decrease in D-Ala-D-Ala. Further structure-activity
      relationships (SARs) studies provided evidence that the hydroxyl substituent in
      the 2-position (R1) of the benzoylthiosemicarbazide scaffold is essential for the
      enzymatic inhibition. This work thus highlights the 1-(2-hydroxybenzoyl)
      thiosemicarbazide motif as a very promising tool for the development of novel
      antibacterial compounds acting through an interesting mechanism of action and low
      cytotoxicity.

PMID- 30300846
TI  - Using summary videos in online classes for nursing students: A mixed methods
      study.
AB  - Online courses need strategies to engage students, especially after a learning
      module is over. We made a series of summary videos for students' assignments and
      investigated their impact on students' learning. This study investigated whether,
      from the students' perspective, summary videos made by teachers for each learning
      module in asynchronized online courses led to students' engagement and feeling of
      being helped. We used exploratory sequential mixed methods research design, which
      started with a qualitative phase. After collecting students' feedback from an
      open-ended question administered to 47 nursing students from 3 online courses, we
      conducted qualitative data analysis. The analysis identified 2 themes: engagement
      and helpfulness. We used these themes to find 2 validated surveys from the
      literature to quantitatively measure students' engagement levels and perceived
      helpfulness of the summary videos. In the quantitative phase, we surveyed 78
      nursing students from 4 online courses 3 times. The results indicated that there
      was no statistically significant difference in students' perceived engagement
      level among the 3 time points, and that students did not believe the helpful
      impact of the summary videos on their learning increased significantly. In the
      mixed methods phase, we compared and contrasted the teaching strategies, quotes
      from the qualitative strand, and results from the statistical analyses of survey
      data. The results indicated that the summary videos were helpful in facilitating
      students' achievement of learning new knowledge and reinforcing previous
      knowledge; engaging students cognitively, emotionally, and socially; and
      motivating students intrinsically. However, the videos did not help with
      students' behavioral engagement and did not help students have a fun learning
      experience. We concluded that the teaching presence in the summary videos created
      the positive and supportive learning environment necessary for giving students
      the opportunity to engage with learning contents.

PMID- 30300847
TI  - Recovery of failing hearts by mechanical unloading: Pathophysiologic insights and
      clinical relevance.
AB  - By reduction of ventricular wall-tension and improving the blood supply to vital
      organs, ventricular assist devices (VADs) can eliminate the major
      pathophysiological stimuli for cardiac remodeling and even induce reverse
      remodeling occasionally accompanied by clinically relevant reversal of cardiac
      structural and functional alterations allowing VAD explantation, even if the
      underlying cause for the heart failure (HF) was dilated cardiomyopathy.
      Accordingly, a tempting potential indication for VADs in the future might be
      their elective implantation as a therapeutic strategy to promote cardiac recovery
      in earlier stages of HF, when the reversibility of morphological and functional
      alterations is higher. However, the low probability of clinically relevant
      cardiac improvement after VAD implantation and the lack of criteria which can
      predict recovery already before VAD implantation do not allow so far VAD
      implantations primarily designed as a bridge to cardiac recovery. The few
      investigations regarding myocardial reverse remodeling at cellular and sub
      cellular level in recovered patients who underwent VAD explantation, the
      differences in HF etiology and pre-implant duration of HF in recovered patients
      and also the differences in medical therapy used by different institutions during
      VAD support make it currently impossible to understand sufficiently all the
      biological processes and mechanisms involved in cardiac improvement which allows
      even VAD explantation in some patients. This article aims to provide an overview
      of the existing knowledge about VAD-promoted cardiac improvement focusing on the
      importance of bench-to-bedside research which is mandatory for attaining the
      future goal to use long-term VADs also as therapy-devices for reversal of chronic
      HF.

PMID- 30300848
TI  - Concurrence of juvenile idiopathic arthritis and primary demyelinating disease in
      a young child.
AB  - CASE REPORT: The association of juvenile idiopathic arthritis (JIA) and primary
      demyelinating disease of central nervous system (CNS) in the same patient is
      rare. Here we present a 10-year-old girl formerly diagnosed with JIA who
      presented with acute total vision loss. Magnetic resonance imaging of the brain
      and spinal cord showed bilateral optic neuritis and T2 hyperintense lesions in
      the brain, cerebellum and cervical spinal cord, some of them gadolinium
      enhancing. Oligoclonal bands were present in the cerebrospinal fluid. Visual
      evoked potentials were prolonged. Aquaporin-4 antibodies were negative. The
      patient was treated with methylprednisolone 30 mg/kg daily for five days,
      resulting in improvement in vision and gait. This first demyelinating event in
      this patient with JIA with clinical and paraclinical features meeting the 2017 MS
      diagnostic criteria supports a possible predisposition to autoimmune disorders.
      CONCLUSION: The concurrence of JIA and multiple sclerosis (MS) has been reported
      in only two adult cases and not in the pediatric population. While JIA and MS are
      two distinct chronic inflammatory diseases, immunogenetic predisposition and
      common environmental triggers might be involved.

PMID- 30300849
TI  - Cardiorespiratory fitness and cognitive processing speed in multiple sclerosis:
      The possible roles of psychological symptoms.
AB  - BACKGROUND: Aerobic exercise training may improve cognitive performance among
      persons with multiple sclerosis (MS). This is largely based on evidence that
      cardiorespiratory fitness (as a cross-sectional surrogate for aerobic exercise
      training) is associated with cognitive processing speed. There may be a set of
      "other" variables (i.e., psychological symptoms) that influences the association
      between cardiorespiratory fitness and cognitive processing speed in MS, and such
      factors should be accounted for when designing optimized exercise rehabilitation
      interventions. METHODS: The primary objective of the present study involved
      examining psychological symptoms of anxiety, depression, pain, and fatigue as
      possible mediators, moderators, or confounders of the association between
      cardiorespiratory fitness and cognitive processing speed. Sixty-two persons
      across the MS disability spectrum completed anxiety, depression, pain, and
      fatigue questionnaires; underwent Symbol Digit Modalities Test administration; as
      well as two separate incremental exercise tests to exhaustion for measurement of
      psychological symptoms, cognitive processing speed, and cardiorespiratory
      fitness, respectively. RESULTS: Depressive symptoms, pain, and fatigue were
      significantly and jointly associated with cardiorespiratory fitness and cognitive
      processing speed (p < .05) based on bivariate correlation analyses. Despite those
      associations, hierarchical linear regression, bivariate correlation, and partial
      correlation analyses indicated that those psychological symptoms were not
      mediators, moderators, or confounders of the cardiorespiratory fitness/cognitive
      processing speed relationship, respectively. CONCLUSION: The present pattern of
      results suggests that aerobic exercise training (via improving cardiorespiratory
      fitness) might improve cognitive processing speed independent of the influence of
      depression, pain, and fatigue. Such results further suggest that having elevated
      depressive symptoms or severe MS-related fatigue might not affect aerobic
      exercise training-related changes in cognitive processing speed, and that
      psychological symptoms might not distort the association between aerobic exercise
      training and changes in cognitive processing speed.

PMID- 30300850
TI  - Atypical Anti-MOG syndrome with aseptic meningoencephalitis and pseudotumor
      cerebri-like presentations.
AB  - OBJECTIVE: To describe 2 atypical cases with Anti-MOG antibody related
      demyelinating syndrome. METHODOLOGY: Case series. RESULTS: We present two cases.
      Case 1 is an 18-year-old woman who presented with headache, blurred vision, and
      papilledema and was initially diagnosed with pseudotumor cerebri syndrome. CSF
      showed mildly elevated opening pressure and lymphocytic pleocytosis and a
      diagnosis of aseptic meningitis was considered. MRI brain and spinal cord
      revealed longitudinally extensive bilateral simultaneous optic neuritis and
      multiple spinal cord lesions. Case 2 is a 28-year old man who presented initially
      with unilateral optic neuritis followed by aseptic meningitis three weeks later
      and subsequently acute disseminated encephalomyelitis (ADEM). Serology was
      positive for Anti-MOG antibody on a cell-based assay in both these cases.
      DISCUSSION: Although bilateral optic neuritis has been well described in MOG
      related disorders, aseptic meningitis and pseudotumor cerebri-like syndromes are
      notable alternate presentations. The presence of eosinophils in the CSF (in the
      first patient) is a unique finding in our case series. CONCLUSION: In a patient
      with an aseptic meningitis like presentation, the presence of optic neuritis,
      brain and/or spinal cord lesions should raise suspicion for an MOG-Ab related
      syndrome.

PMID- 30300852
TI  - Control of bovine mastitis in the 21st century: Immunize or tolerize?

PMID- 30300851
TI  - Resolution of inflammation in neuromyelitis optica spectrum disorders.
AB  - BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are a spectrum of
      neuroinflammatory disorders associated with autoimmune antibodies against
      aquaporin-4 (AQP4). Accumulating evidence suggests that inflammation is involved
      in NMOSD pathogenesis. Resolution of inflammation, which is a highly regulated
      process mediated by specialized pro-resolving lipid mediators (SPMs) is important
      to prevent over-responsive inflammation. Deficiency in resolution of inflammation
      may lead to or accelerates inflammatory diseases. However, whether resolution of
      inflammation is impaired in NMOSD is not known. The objective of this study was
      to analyze the levels of SPMs in the serum and cerebrospinal fluid (CSF) of NMOSD
      patients, and to explore the roles of SPMs in clinical features of NMOSD.
      METHODS: Thirty-five patients with NMOSD, 34 patients with multiple sclerosis,
      and 36 patients with non-inflammatory neurological diseases were enrolled in this
      study. Pro-resolving mediators including Annexin A1 (ANXA1) and resolvin D1
      (RvD1), as well as pro-inflammatory lipid mediator leukotriene B4 (LTB4) levels
      were analyzed by enzyme-linked immunosorbent assay. Pro- and anti-inflammatory
      cytokines as well as chemokine levels were analyzed using cytometric beads array
      (CBA). RESULTS: Our results showed RvD1 levels were significantly decreased,
      whereas LTB4 levels were significantly increased in the CSF of NMOSD patients.
      AQP4-IgG titer was negatively correlated with RvD1 levels in the CSF of NMOSD
      patients. CONCLUSIONS: Decreased RvD1 levels indicate impaired resolution of
      inflammation in NMOSD patients. AQP4-IgG may contribute to increased inflammation
      and lead to unresolved inflammation in NMOSD.

PMID- 30300853
TI  - Protection efficacy of Argentinian isolates of Mycobacterium avium subsp.
      paratuberculosis with different genotypes and virulence in a murine model.
AB  - Paratuberculosis is a chronic disease caused by Mycobacterium avium subsp.
      paratuberculosis (Map). The disease causes economic losses and, therefore, it is
      imperative to follow proper control strategies, which should include an effective
      vaccine. Several strategies have assessed the virulence and immune response of
      Map strains that could be used as a vaccine. This study evaluates the degree of
      virulence, immune response, and protection of Argentinian strains of Map with
      different genotype in a murine model. Four local isolates (Cattle type) with
      different genotypes (analyzed by MIRU-VNTR and SSRs) were selected and evaluated
      in a virulence assay in BALB/c mice. This assay allowed us to differentiate
      virulent and low-virulence Map strains. The less virulent strains (1543/481 and
      A162) failed to induce a significant production of the proinflammatory cytokine
      IFNg, whereas the virulent strain 6611 established infection along with a
      proinflammatory immune response. On the other hand, the virulent strain 1347/498
      was efficient in establishing a persistent infection, but failed to promote an
      important Th1 response compared with 6611 at the evaluated time. We selected the
      low-virulence strain 1543/498 as a live vaccine and the virulent strain 6611 as a
      live and inactivated vaccine in a protection assay in mice. Strain 1543/481
      failed to protect the animals from challenge, whereas strain 6611, in its live
      and inactivated form, significantly reduced the CFUs count in the infected mice,
      although they had different immunological response profiles. The inactivated
      virulent strain 6611 is a potential vaccine candidate against paratuberculosis to
      be tested in cattle.

PMID- 30300854
TI  - Inflammation and coronary artery disease: The exercise paradox.

PMID- 30300855
TI  - Distinct mechanisms regulate IL1B gene transcription in lymphoid CD4 T cells and
      monocytes.
AB  - Interleukin 1beta is a pro-inflammatory cytokine important for both normal immune
      responses and chronic inflammatory diseases. The regulation of the 31 kDa proIL
      1beta precursor coded by the IL1B gene has been extensively studied in myeloid
      cells, but not in lymphoid-derived CD4 T cells. Surprisingly, we found that some
      CD4 T cell subsets express higher levels of proIL-1beta than unstimulated
      monocytes, despite relatively low IL1B mRNA levels. We observed a significant
      increase in IL1B transcription and translation in CD4 T cells upon ex vivo
      CD3/CD28 activation, and a similar elevation in the CCR5+ effector memory
      population compared to CCR5- T cells in vivo. The rapid and vigorous increase in
      IL1B gene transcription for stimulated monocytes has previously been associated
      with the presence of Spi-1/PU.1 (Spi1), a myeloid-lineage transcription factor,
      pre-bound to the promoter. In the case of CD4 T cells, this increase occurred
      despite the lack of detectable Spi1 at the IL1B promoter. Additionally, we found
      altered epigenetic regulation of the IL1B locus in CD3/CD28-activated CD4 T
      cells. Unlike monocytes, activated CD4 T cells possess bivalent
      H3K4me3+/H3K27me3+ nucleosome marks at the IL1B promoter, reflecting low
      transcriptional activity. These results support a model in which the IL1B gene in
      CD4 T cells is transcribed from a low-activity bivalent promoter independent of
      Spi1. Accumulated cytoplasmic proIL-1beta may ultimately be cleaved to mature 17
      kDa bioactive IL-1beta, regulating T cell polarization and pathogenic chronic
      inflammation.

PMID- 30300856
TI  - Long-term outcome and necessity of liver transplantation in infants with biliary
      atresia are independent of cytokine milieu in native liver and serum.
AB  - PURPOSE: Biliary atresia (BA) is a rare disease of unknown pathogenesis in
      infants characterized by an inflammatory, progressive destruction of the biliary
      system and deterioration of liver function. The standard treatment for BA is a
      Kasai-hepatoportoenterostomy (KPE). However, liver transplantation (LTX) becomes
      necessary in about 50-80% of cases. Therefore, some authors advocate for primary
      LTX in BA, but this would require early markers to predict which children would
      benefit from KPE or to show rapid progression to liver cirrhosis (RLC) instead.
      METHODS: Snap-frozen liver biopsies and sera samples of 57 infants with BA were
      collected during KPE. Clinical and follow-up data were assessed via the biliary
      atresia and related diseases registry (BARD-online.com). Protein-levels of 25 pro
      and anti-inflammatory mediators of 49 infants were assessed via multiplex
      protein-immunoassay and analyzed by t-test as well as multidimensional principal
      component analysis. RESULTS: 22 different immunomodulatory mediators were
      detectable in livers of children with BA, while serum protein levels were very
      low to undetectable. Following KPE, 33 BA patients showed RLC that required early
      LTX, while 24 had favorable course of disease with long-term survival with native
      liver (SNL). There were no significant differences between RLC and SNL in terms
      of local (from liver samples) nor systemic (from sera) immunomodulatory
      mediators. Protein levels were much lower in sera than in livers without
      statistical correlation. CONCLUSION: Our data suggest that local or systemic
      immunomodulatory mediators are unsuitable for predicting the disease course of
      BA. Thus, no deduction for optimal treatment strategy can be drawn. Collectively,
      we conclude that in BA, the degree of inflammation and protein microenvironment
      in the liver at the time-point of KPE are dismissible factors for the future
      course of disease.

PMID- 30300857
TI  - Recruiting, integrating, and sustaining stakeholder participation in
      environmental management: A case study from the Great Lakes Areas of Concern.
AB  - Stakeholder participation is now widely viewed as an essential component of
      environmental management projects, but limited research investigates how
      practitioners perceive the major challenges and strategies for implementing high
      quality participation. In order to address this gap, we present findings from a
      survey and interviews conducted with managers and advisory committee leaders in a
      case study of United States and binational (US and Canada) Great Lakes Areas of
      Concern. Our findings suggest that recruiting and integrating participants and
      sustaining participation over the long term present distinctive ongoing
      challenges that are not fully recognized in existing conceptualizations of the
      process of implementing participation. For example, it can be difficult to
      recruit active stakeholders to fill vacant "slots," to integrate distinctive
      interests and perspectives in decision-making processes, and to keep participants
      involved when activity is low and less visible. We present strategies that
      emerged in the survey and interviews for addressing these challenges, emphasizing
      the building and leveraging of relationships among stakeholders themselves. Such
      strategies include balancing tight networks with an openness to new members,
      supplementing formal hearings with social gatherings, making participation
      socially meaningful, and dividing labor between managers and advisory committees.

PMID- 30300858
TI  - Potential development of Irish agricultural sustainability indicators for current
      and future policy evaluation needs.
AB  - There is a significant and detailed range of sustainability indicators for Irish
      agri-food production, but there remain areas where further indicator development
      or new indicators could prove valuable. This review provides an outline of
      potential developments in Irish assessment of agricultural sustainability
      following the latest research and in order to meet policy demands. Recent
      research findings have suggested means of improved quantitative modelling of
      greenhouse gas emissions, but additional dietary and soil data may be important
      for this, especially for the potential inclusion of any soil sequestration. This
      information could also benefit more detailed modelling of nutrient losses to
      water. Specific concerns over pesticide and antibiotic use may require additional
      survey work on the particular locations or types of farms of interest.
      Biodiversity monitoring could be improved by expanding the range of results
      oriented agri-environment schemes or employing remote-sensing habitat monitoring,
      likely supplemented with targeted field surveys for specific objectives. Farm
      level economic sustainability is largely well-covered, but additional data
      collection may be of benefit to address specific issues such as labour costs.
      Recent additional surveys on farm-level social sustainability have addressed
      important social indicators of isolation and access to local services, and could
      be rolled out on a larger number of farms in the future. Wider societal concerns
      such as animal welfare, genetically modified materials in foodstuffs and
      antibiotic resistance have limited indicators currently available, and could also
      benefit from additional surveys. The breadth and detail required in agri-food
      sustainability indicators present a significant challenge to survey design and
      implementation, but many developments can be achieved without additional surveys
      through the use of remote sensing and geospatial technologies and integration of
      existing datasets. Despite the important benefits of further developments in
      Irish sustainability indicators, consideration must also be given to farmer
      confidentiality and survey fatigue.

PMID- 30300859
TI  - Biochar amendment and water stress alter rhizosphere carbon and nitrogen budgets
      in bauxite-processing residue sand under rehabilitation.
AB  - Nitrogen (N) bioavailability is one of the main limiting factors for microbial
      activity and vegetation establishment in bauxite-processing residue sand (BRS).
      Although beneficial effects of biochar on reducing N loss in the early stages of
      BRS rehabilitation have been observed previously, the underlying mechanisms of
      this complicated process, particularly the interactions between applied biochar
      and the plant rhizosphere is largely unknown. This glasshouse study (116 days),
      investigated the coupled effects of biochar and water stress on N bioavailability
      in the rhizosphere of ryegrass (Lolium rigidum) grown in BRS amended with di
      ammonium phosphate (DAP) fertiliser (at rates of 0 or 2.7 t ha-1) with and
      without biochar amendment. The applied biochar was characterised as either aged
      acidic (AC) or alkaline pine (PC) and was mixed with BRS at a rate of 5% v/v
      under four moisture regimes (50%, 40%, 20% and 7.5% water holding capacity).
      Amending BRS with AC and PC biochars increased NH4+ retention and decreased
      cumulative NH3 volatilization within both the rhizosphere and root-free zones
      compared with fertiliser only treatment. These effects were more pronounced for
      the AC than PC biochar, suggesting that aged acidic biochar has the great
      potential for use in rapid establishment of vegetation in BRS disposal areas. The
      biochar amendment increased cumulative nitrous oxide emissions compared with DAP
      only treatment, with no significant differences among different moisture regimes.
      The Control and 20% water holding capacity (WHC) treatment showed the highest
      dissolved organic carbon (DOC) concentrations compared with other treatments and
      moisture regimes in the ryegrass rhizosphere, while the highest dissolved organic
      N concentration were observed in the DAP + AC treatment. Reducing moisture levels
      below 20% WHC generally decreased microbial biomass carbon (MBC) concentrations
      and activity in both the rhizosphere and root-free zones of all treatments, while
      total N generally decreased as moisture levels decreased from 50% to 7.5% WHC.
      Plant took up more N in the DAP + AC treatment compared with DAP + PC and DAP
      only treatments, while increasing water stress generally resulted in decreased
      aboveground biomass.

PMID- 30300860
TI  - High resolution spectroscopy on Te2: New lines for reference.
AB  - Ro-vibrational spectra of different electronic states of molecules are often used
      as absolute wavelength or frequency standards. These standards are also used to
      mitigate any slow drift of laser frequency during an experiment. In the precision
      experiment, the two most commonly used molecular standards are iodine and
      tellurium, both are homo-nuclear diatomic molecules. The former is mostly used as
      standard for the long wavelength (600-900 nm) region, while the tellurium
      spectrum is widely used in short wavelength (400-550 nm) including near
      ultraviolet. A comprehensive data on tellurium spectra can be obtained from the
      tellurium atlas [1]. However near the 455 nm range where a number of important
      atomic resonance line, the atlas provides no significant data. We have performed
      high resolution modulation transfer spectroscopy (MTS) on tellurium molecule in a
      hot cell in the region close to 455 nm wavelength thereby obtained more than 100
      new spectral lines which were not observed before. The linewidth of each of these
      peaks is about a few tens of MHz, making them suitable for laser frequency
      locking.

PMID- 30300861
TI  - Design and optimization of a luminescent Samarium complex of isoprenaline: A
      chemometric approach based on Factorial design and Box-Behnken response surface
      methodology.
AB  - A chemometrically optimized procedure has been developed for the determination of
      isoprenaline (ISO) in the parent substance as well as in its respective
      pharmaceutical preparation. It is worth mentioning that although spectroscopic
      determination of Isoprenaline metal complexes has been described in literature,
      yet, no methods for the quantification of Isoprenaline with Samarium nor any
      other lanthanide metal have been reported. Fractional factorial design (FFD) was
      implemented in the initial screening procedure of the four designated factors,
      namely, reaction time (RT), metal volume (MV), pH and temperature (T) followed by
      Response Surface Methodology (RSM) optimization tool performed by the aid of Box
      Behnken design (BBD).The proposed techniques are based on a multivariate approach
      where a complexation reaction between Isoprenaline (ISO) and Samarium III (Sm3+)
      metal was exploited for the first time to synthesize novel fluorescence and
      absorbance probes of ISO-Sm. Maximum fluorescence intensity (Y1) as well as
      maximum absorbance (Y2) of the produced complex were attained at
      lambdaex/lambdaem = 315/450 and lambda 295 nm for spectrofluorimetric and
      spectrophotometric determinations, respectively, against blank solutions. Using
      assessment quality tools such as, Pareto charts, normal probability plots and
      statistical analysis of variance testing (ANOVA), significant factors were
      successfully indicated (p < 0.05). Furthermore, the proposed methods verified
      specificity and accuracy for the determination of Isoprenaline in its pure and
      pharmaceutical preparation using spectrofluorimetric (Technique A) and
      spectrophotometric (Technique B) techniques, respectively. Linearity was obtained
      in the range of (0.02-0.50 MUg/mL) and (2-12 MUg/mL) upon employing both
      techniques A and B, respectively. Furthermore, limit of detection (LOD) and limit
      of quantification (LOQ), were found to be 5.1877 * 10-3 MUg/mL, 0.01572 MUg/mL
      and 0.5593 MUg/mL, 1.6949 MUg/mL, upon employing techniques A and B,
      respectively. Standard addition method was applied for both techniques. The
      analysis was successfully applied to the assay of pure powder and pharmaceutical
      dosage forms after which the corresponding mean recoveries were computed and were
      found to be in the range of 99.546%-100.257% (Technique A) and 99.872%-99.887%
      (Technique B) with RSD (<1).

PMID- 30300863
TI  - Effect of nonpharmacological interventions for the prevention of delirium in the
      intensive care unit: A systematic review and meta-analysis.
AB  - PURPOSE: We aimed to classify nonpharmacological interventions used for
      preventing delirium in the intensive care unit (ICU), and estimate their effect
      size. MATERIALS AND METHODS: In this systematic review and meta-analysis, the
      literature was searched and studies were selected based on the PRISMA flow chart.
      Data sources included MEDLINE, Cochrane, CINHAHL, PsyInfo, and EMBASE. We used
      Cochrane's Effective Practice and Organisation of Care (EPOC) criteria in study
      design and quality assessment of the meta-analysis. RESULTS: This systematic
      review and meta-analysis included 35 and 15 studies, respectively. Studies were
      grouped into nine intervention types: multicomponent (16 studies), physical
      environment (9), daily interruption of sedation (2), exercise (2), patient
      education (2), automatic warning system (1), cerebral hemodynamics improving (1),
      family participation (1), and sedation reducing protocol (1). The effect size of
      preventive nonpharmacological interventions had an odds ratio (OR) of 0.66 (95%
      confidence interval [CI], 0.50-0.86) for delirium occurrence, and an OR of 0.31
      (95% CI, 0.10-0.94) for delirium duration. Although relevant studies by
      interventions were lacking, a partial subgroup analysis by intervention was
      performed. CONCLUSIONS: Nonpharmacological interventions were effective in
      reducing the duration and occurrence of delirium. Consistent application and
      development of nonpharmacological interventions for use in the ICU are important.

PMID- 30300862
TI  - Apoptosis inducing factor deficiency causes retinal photoreceptor degeneration.
      The protective role of the redox compound methylene blue.
AB  - Dysfunction in mitochondrial oxidative phosphorylation (OXPHOS) underlies a wide
      spectrum of human ailments known as mitochondrial diseases. Deficiencies in
      complex I of the electron transport chain (ETC) contribute to 30-40% of all cases
      of mitochondrial diseases, and leads to eye disease including optic nerve atrophy
      and retinal degeneration. The mechanisms responsible for organ damage in
      mitochondrial defects may include energy deficit, oxidative stress, and an
      increase in the NADH/NAD+ redox ratio due to decreased NAD+ regeneration.
      Currently, there is no effective treatment to alleviate human disease induced by
      complex I defect. Photoreceptor cells have the highest energy demand and
      dependence on OXPHOS for survival, and the lowest reserve capacity indicating
      that they are sensitive to OXPHOS defects. We investigated the effect of
      mitochondrial OXPHOS deficiency on retinal photoreceptors in a model of
      mitochondrial complex I defect (apoptosis inducing factor, AIF-deficient mice,
      Harlequin mice), and tested the protective effect of a mitochondrial redox
      compound (methylene blue, MB) on mitochondrial and photoreceptor integrity. MB
      prevented the reduction in the retinal thickness and protein markers for
      photoreceptor outer segments, Muller and ganglion cells, and altered
      mitochondrial integrity and function induced by AIF deficiency. In rotenone
      induced complex I deficient 661 W cells (an immortalized mouse photoreceptor cell
      line) MB decreased the NADH/NAD+ ratio and oxidative stress without correcting
      the energy deficit, and improved cell survival. MB deactivated the mitochondrial
      stress response pathways, the unfolding protein response and mitophagy. In
      conclusion, preserving mitochondrial structure and function alleviates retinal
      photoreceptor degeneration in mitochondrial complex I defect.

PMID- 30300864
TI  - A method to quantify intracellular glycation in dermal fibroblasts using liquid
      chromatography coupled to fluorescence detection - Application to the selection
      of deglycation compounds of dermatological interest.
AB  - Glycation is a common non-enzymatic reaction between proteins and sugars, which
      gives rise in the human body to the formation of advanced glycation end products
      (AGEs). These modifications impacts both extra and intracellular proteins,
      leading to cells and tissues dysfunctions. In the skin, accumulation of AGEs
      leads to aesthetic consequences, wrinkles, dark spots and yellowish skin tone, as
      it can be seen in diabetic patients. Consequently, there is a growing
      dermatological interest to find compounds able to eliminate AGEs accumulated in
      skin. In this context, a method has been developed to detect and quantify
      intracellular glycation in human dermal fibroblasts. After cultivation of
      fibroblasts, cell lysates were injected in an HPLC system coupled with a
      fluorescence detector in by-pass mode. The system allows the simultaneous
      measurement of global AGEs and particular pentosidine amounts using two sets of
      wavelengths in a single run of 1 min. The immunocytochemistry approach was used
      to valid the HPLC analysis data. The method developed was able to quantify
      changes in global AGEs and pentosidine content in cells in response to glyoxal
      treatment. Fibroblasts treated with 500 MUM of glyoxal for 48 h showed a
      significant 2.3-fold and 2.6-fold increase in the content of AGEs and pentosidine
      respectively compared to control cells. As an application, a screening of natural
      extracts have been done and the method allowed identifying extracts able to
      significantly reduce the amount of pentosidine in fibroblasts (-32%). These
      extracts act as deglycation agents of interest in the field of dermatology and
      cosmetology.

PMID- 30300865
TI  - DNA methylation of the ELOVL2, FHL2, KLF14, C1orf132/MIR29B2C, and TRIM59 genes
      for age prediction from blood, saliva, and buccal swab samples.
AB  - Many studies have reported age-associated DNA methylation changes and age
      predictive models in various tissues and body fluids. Although age-associated DNA
      methylation changes can be tissue-specific, a multi-tissue age predictor that is
      applicable to various tissues and body fluids with considerable prediction
      accuracy might be valuable. In this study, DNA methylation at 5 CpG sites from
      the ELOVL2, FHL2, KLF14, C1orf132/MIR29B2C, and TRIM59 genes were investigated in
      448 samples from blood, saliva, and buccal swabs. A multiplex methylation
      SNaPshot assay was developed to measure DNA methylation simultaneously at the 5
      CpG sites. Among the 5 CpG sites, 3 CpG sites in the ELOVL2, KLF14 and TRIM59
      genes demonstrated strong correlation between DNA methylation and age in all 3
      sample types. Age prediction models built separately for each sample type using
      the DNA methylation values at the 5 CpG sites showed high prediction accuracy
      with a Mean Absolute Deviation from the chronological age (MAD) of 3.478 years in
      blood, 3.552 years in saliva and 4.293 years in buccal swab samples. A tissue
      combined model constructed with 300 training samples including 100 samples from
      each blood, saliva and buccal swab samples demonstrated a very strong correlation
      between predicted and chronological ages (r = 0.937) and a high prediction
      accuracy with a MAD of 3.844 years in the 148 independent test set samples of 50
      blood, 50 saliva and 48 buccal swab samples. Although more validation might be
      needed, the tissue-combined model's prediction accuracies in each sample type
      were very much similar to those obtained from each tissue-specific model. The
      multiplex methylation SNaPshot assay and the age prediction models in our study
      would be useful in forensic analysis, which frequently involves DNA from blood,
      saliva, and buccal swab samples.

PMID- 30300866
TI  - Attempting to discontinue antipsychotic medication: Withdrawal methods, relapse
      and success.
AB  - Few studies explore subjective experiences of attempting to discontinue
      antipsychotic medication, the withdrawal methods people use, or how their efforts
      affect their outcomes. People who take antipsychotics for off-label purposes are
      poorly represented in the literature. This study investigates experiences of
      attempting to discontinue antipsychotics in a cross-sectional sample and explores
      potential associations between withdrawal methods, relapse, and success. An
      anonymous online survey was completed by 105 adults who had taken antipsychotics
      for any reason and had attempted discontinuation at least once. A mixed methods
      approach was used to interpret the responses. Just over half (55.2%) described
      successfully stopping for varying lengths of time. Half (50.5%) reported no
      current use. People across diagnostic groups reported unwanted withdrawal
      effects, but these were not universal. Withdrawing gradually across more than one
      month was positively associated, and relapse was negatively associated with both
      self-defined successful discontinuation and no current use. Gradual withdrawal
      was negatively associated with relapse during withdrawal. We conclude it is
      possible to successfully discontinue antipsychotic medication, relapse during
      withdrawal presents a major obstacle to successfully stopping AMs, and people who
      withdraw gradually across more than one month may be more likely to stop and to
      avoid relapse during withdrawal.

PMID- 30300867
TI  - Social anhedonia and asociality in psychosis revisited. An experience sampling
      study.
AB  - The DSM-5 appended the conceptualization of asociality in psychotic disorders as
      the manifestation of diminished interest in social interactions, but it also
      admitted that it might merely be the result of limited opportunities for social
      interactions. In an effort to investigate this apparent dichotomy, we used
      experience sampling data from 149 patients with psychotic disorder and 143
      controls, and divided their social interactions into those occurring in the
      context of work and other structured activities that patients have limited access
      to, and those occurring in the context of unstructured activities such as visits
      and conversations that both groups can choose relatively more freely. Patients
      spent significantly smaller proportion of their time in structured social
      context, but matched the controls in the time spent in unstructured social
      contexts, and endorsed intact hedonic experience of both social contexts.
      Moreover, employment and living situation, in addition to the severity of
      symptoms of avolition, predicted the proportion of time patients spent in
      structured and unstructured social contexts, supporting the notion that both
      lifestyle as well as disease-specific factors contribute to real-life social
      behavior in psychosis.

PMID- 30300868
TI  - Detection of patients with methamphetamine dependence with cue-elicited heart
      rate variability in a virtual social environment.
AB  - In the present study, we developed a methamphetamine (METH)-related virtual
      social environment to elicit subjective craving and physiological reactivity.
      Sixty-one male patients who were abstinent from METH use and 45 age-matched
      healthy males (i.e., normal controls) were recruited. The physiological
      electrocardiogram (ECG) signals were recorded before (resting-state condition)
      and during viewing of a METH-cue video in the virtual environment (cue-induced
      condition). The cue-induced subjective craving was measured with a visual
      analogue scale (VAS) for patients with METH dependence. The results indicated
      that the cue-induced condition elicited significant differences in heart rate
      variability (HRV) between patients with METH dependence and normal controls. The
      changes of HRV indexes on time domain and non-linear domain from the resting
      state condition to the cue-induced condition were positively correlated with the
      score on VAS of METH craving. Using a supervised machine learning algorithm with
      the features extracted from HRV changes, our results showed that the discriminant
      model provided a high predictive power for distinguishing patients with METH
      dependence from normal controls. Our findings support that immersing subjects
      with METH dependence in a METH-related virtual social environment can
      successfully induce physiological reactivity, and cue-induced physiological
      signal changes may have a potential implication in clinical practice.

PMID- 30300869
TI  - Body-focused repetitive behaviors: More prevalent than once thought?
AB  - Body-focused repetitive behaviors (BFRBs), such as hair pulling, skin picking,
      and nail biting are common habits, but their pathological manifestations have
      been considered rare. Growing evidence suggests pathological forms of these
      behaviors can be conceptualized as a class of related disorders. However, few
      previous studies have examined the collective prevalence of related pathological
      BFRBs. The current study examined the self-reported prevalence of current (past
      month) subclinical and pathological BFRBs in a large (n = 4335) sample of college
      students. The study also examined the chronicity and impact of these behaviors.
      Results showed that 59.55% of the sample reported occasionally engaging in
      subclinical BFRBs, and 12.27% met criteria for a pathological BFRB, suggesting
      these conditions may be quite common. Of the various BFRB topographies, cheek
      biting was the most common. Both subclinical and pathological BFRBs tended to be
      chronic (i.e., occurring for longer than 1 year). Although persons with
      pathological BFRBs were distressed about their behavior, few experienced
      functional impairment or sought help for the behavior. Implications of these
      findings for the conceptualization and treatment of body-focused repetitive
      behaviors are discussed.

PMID- 30300870
TI  - An evaluation of a low intensity mHealth enhanced mindfulness intervention for
      Chinese university students: A randomized controlled trial.
AB  - Mental disorders and sleep dysfunction are common among Chinese university
      students. This study aimed to evaluate a low cost scalable mindfulness
      intervention program to improve psychological health and sleep quality among
      Chinese university students. A randomized controlled trial with 101 university
      students (mean age 22.30 +/- 2.63, 69.31% female) was conducted. Participants
      were randomized into 4 groups: Group 1: control group (n = 25), Group 2:
      mindfulness only group (n = 27), Group 3: mindfulness + plain-text reminder group
      (n = 24), and Group 4: mindfulness + enhanced text reminder with animal meme
      group (n = 25).The mindfulness intervention consisted of two in-person guided
      sessions along with weekly self-guided practice for 7 weeks. The Depression,
      Anxiety and Stress Scale (DASS-21) and The Pittsburgh Sleep Quality Index (PSQI)
      were used to measure depression, anxiety, stress, and sleep dysfunction. After
      the intervention at week 4, compared to controls, completers in group 2, 3 and 4
      (n = 42) showed significantly reduced depression (Cohen's d = 0.83), anxiety
      (Cohen's d = 0.84), and stress (Cohen's d = 0.75), and improved subjective sleep
      quality (Cohen's d = 2.00), sleep latency (Cohen's d = 0.55), and habitual sleep
      efficiency (Cohen's d = 0.86). The effect was maintained at week 7. Low-intensity
      mindfulness interventions might be a useful intervention program in university
      settings.

PMID- 30300871
TI  - MINDSET: Clinical feasibility of utilizing the revised epilepsy self-management
      tool for Spanish speaking patients.
AB  - This paper describes the expanded English/Spanish version of the Management
      Information and Decision Support Epilepsy Tool (MINDSET) as well as the methods
      and findings from a feasibility study conducted from July 2016 through February
      2017 with 43 Spanish and English-speaking Hispanic people living with epilepsy
      (PWE) in Arizona (n = 23) and Texas (n = 20) over two consecutive regular clinic
      visits. The expansion of MINDSET added goal setting and strategy selection to
      improve self-management (S-M) in PWE. The previous study tested the feasibility
      of English MINDSET, which was designed to facilitate the identification and
      discussion of S-M issues between the patient and healthcare provider (HCP) during
      a regular clinic visit. Results indicate MINDSET feasibility for use in the
      following: 1) identifying S-M issues across several domains; 2) selecting and
      assessing confidence in tailored S-M goals/strategies for improvement; 3)
      discussing S-M issues/goals/strategies/confidence with a HCP; and 4) creating an
      action plan (AP) and tracking achievement during regular clinic visits. Across
      two visits, 80-90% of patients agreed that the revised version of MINDSET was
      helpful, understandable, trustworthy, promoted careful thinking about management,
      was of appropriate duration, and would be helpful in future management and
      communication with HCP. Participating HCPs agreed that MINDSET improved the ease,
      thoroughness, and accuracy in identifying patient S-M issues and establishing a
      plan for improvement.

PMID- 30300872
TI  - Priority substances in accumulated sediments in a stormwater detention basin from
      an industrial area.
AB  - One of the most adopted solutions in developed countries to manage stormwater is
      detention/retention basins which generate large quantities of sediments that have
      to be removed regularly. In order to manage them properly, accurate data are
      needed about their physical and chemical characteristics, particularly on
      micropollutant concentrations and their associated risk. This work consisted in a
      two-year sampling of dry sediments from a detention-settling basin. Priority
      substances, including pesticides, polybrominated diphenyl ethers (PBDE),
      alkylphenols and bisphenol A (BPA), were monitored. Different sites in the basin
      bottom were sampled in order to investigate spatial distribution of the
      contamination. Results show that the increase of the sediment thickness in the
      basin was heterogeneous with a maximum of 15 cm after two years. Pesticides and
      PBDE were, if detected, mainly found in low concentrations from 2 ng/g to 286
      ng/g. Conversely, alkylphenols and bisphenol A were always quantified at
      concentrations varying from 6 ng/g to 3400 ng/g. These high levels suggest that
      these sediments should be managed with precautions. Spatial heterogeneity of
      alkylphenol ethoxylates and BPA concentrations was observed, with higher
      contamination of alkylphenol ethoxylates in anaerobic zones and BPA levels
      correlated with total organic carbon and in a lesser extent to fine particles.

PMID- 30300873
TI  - Oxidative potential of fine ambient particles in various environments.
AB  - The oxidative potential (OP) and chemical characteristics of fine particles
      collected from urban, roadside, rural, and industrial sites in Korea during
      spring, summer, fall, and winter seasons and an urban site in the Philippines
      during dry and wet seasons were examined. Significant differences in the OP of
      fine particles among sites and seasons were found. The industrial site yielded
      the highest OP activity (both mass and volume-normalized OP) among the sites,
      suggesting the strongest reactive oxygen species (ROS)-generating capability of
      industry source-dominant PM2.5. Seasonal data show that OP activities increased
      during the spring and summer possibly due to increased heavy metals caused by
      dust events and secondary organic aerosols formed by strong photochemical
      activity, respectively. The strength of the OP association with the chemical
      components highlights the influence of organic carbon and transition metals on
      the OP of ambient fine particles. The two OP assays (dithiothreitol (DTT) and
      electron spin resonance (ESR)) having different ROS-generating mechanisms were
      found to have different sensitivities to the chemical components facilitating a
      complementary analysis of the OP of ambient fine particles. Multiple linear
      regression model equations (OP as a function of chemical components) which were
      dependent on the sites were derived. A comparison of the daily OP and hazard
      index (HI) (the ratio of the measured mass concentration to the reference mass
      concentration of fine particles) suggests that the HI may not be sufficient to
      accurately estimate the health effects of fine particles, and a direct or
      indirect measurement of toxicity such as OP should be required in addition to the
      concentration level.

PMID- 30300874
TI  - Dendritic spine loss caused by AlCl3 is associated with inhibition of the Rac
      1/cofilin signaling pathway.
AB  - Aluminum (Al) has neurotoxicity that can result in cognitive dysfunction.
      Hippocampal dendritic spine loss is a pathological characteristic of cognitive
      dysfunction. Our previous study reported that Al exposure caused dendritic spine
      loss in the hippocampus, but the underlying mechanism remains unclear. In this
      study, rats were orally administered 50, 150 or 450 mg/kg of AlCl3 for 90 days.
      The dendritic spine density of the CA1 and DG regions was detected by Golgi-Cox
      staining. The F-actin/G-actin ratio, the expression of drebrin A and the
      components of the Rac 1/cofilin pathway were measured in the hippocampus. The
      results obtained showed that AlCl3 caused dendritic spine loss and decreased the
      F-actin/G-actin ratio. In addition, it was found that AlCl3 downregulated the
      expression of Rac 1, p-PAK, p-LIMK, p-cofilin and drebrin A and upregulated
      cofilin expression. Altogether, these results demonstrated that Al inactivated
      the Rac 1/cofilin pathway by inhibiting the phosphorylation of cofilin and the
      polymerization of F-actin, resulting in dendritic spine loss in the hippocampus.

PMID- 30300875
TI  - A rationale for the high limits of quantification of antibiotic resistance genes
      in soil.
AB  - The determination of values of abundance of antibiotic resistance genes (ARGs)
      per mass of soil is extremely useful to assess the potential impacts of relevant
      sources of antibiotic resistance, such as irrigation with treated wastewater or
      manure application. Culture-independent methods and, in particular, quantitative
      PCR (qPCR), have been regarded as suitable approaches for such a purpose.
      However, it is arguable if these methods are sensitive enough to measure ARGs
      abundance at levels that may represent a risk for environmental and human health.
      This study aimed at demonstrating the range of values of ARGs quantification that
      can be expected based on currently used procedures of DNA extraction and qPCR
      analyses. The demonstration was based on the use of soil samples spiked with
      known amounts of wastewater antibiotic resistant bacteria (ARB) (Enterococcus
      faecalis, Escherichia coli, Acinetobacter johnsonii, or Pseudomonas aeruginosa),
      harbouring known ARGs, and also on the calculation of expected values determined
      based on qPCR. The limits of quantification (LOQ) of the ARGs (vanA, qnrS,
      blaTEM, blaOXA, blaIMP, blaVIM) were observed to be approximately 4 log-units per
      gram of soil dry weight, irrespective of the type of soil tested. These values
      were close to the theoretical LOQ values calculated based on currently used DNA
      extraction methods and qPCR procedures. The observed LOQ values can be considered
      extremely high to perform an accurate assessment of the impacts of ARGs
      discharges in soils. A key message is that ARGs accumulation will be noticeable
      only at very high doses. The assessment of the impacts of ARGs discharges in
      soils, of associated risks of propagation and potential transmission to humans,
      must take into consideration this type of evidence, and avoid the simplistic
      assumption that no detection corresponds to risk absence.

PMID- 30300876
TI  - Effectiveness End Points in Real-World Studies on Biological Therapies in
      Psoriasis: Systematic Review with Focus on Drug Survival.
AB  - Psoriasis is a complex and chronic disease, and, in most cases, therapies are
      required during all patients' lifetime. The efficacy and safety profiles of
      biological therapies are well established, but their effectiveness is still open
      to discussion. We performed a systematic review to summarize how the
      effectiveness of biological therapies for psoriasis is measured in real-world
      studies and to understand whether drug survival, a recent alternative outcome to
      clinical ones, is a recurrent and valid outcome of effectiveness. In March 2017,
      we searched for quantitative epidemiological data of psoriasis treatments using
      PubMed/Medline and EMBASE, and we included 65 publications. The retrospective
      study design (37%) was most frequent, followed by prospective registries (29%),
      prospective studies (19%), and retrospective administrative databases/claims.
      Drug survival was reported in over 60% of prospective registries and
      retrospective studies, and less frequently in prospective studies. A general
      consensus emerged in the definition of drug survival as the time patients remain
      under treatment with a specific therapy, and in its interpretation as an overall
      marker of treatment success and treatment adherence, as it represents
      simultaneously information on drug efficacy, drug safety, and patient
      satisfaction. In conclusion, notwithstanding some limitations, drug survival is a
      useful measurement of biological therapy effectiveness for psoriasis in daily
      practice. Its major advantage is that it can be computed also in already
      collected databases without any specific clinical information on psoriasis. This
      outcome, combined with evidence on clinical markers of effectiveness, can
      contribute to better understanding the performance of this expensive class of
      drugs.

PMID- 30300877
TI  - To Wash or Not to Wash? Comparison of Patient Outcome after Infusion of
      Cryopreserved Autologous Hematopoietic Stem Cells before and after the
      Replacement of Manual Washing by Bedside Thawing.
AB  - BACKGROUND: Prior to infusion, cryopreserved autologous peripheral blood stem
      cell (auto-PBSC) grafts can either be thawed at the bedside or thawed and washed
      at the laboratory. At our center, manual washing of grafts prior to infusion was
      discontinued in April 2012 and bedside thawing was implemented. METHODS: This
      study compares the outcomes of two patient groups who received auto-PBSC either
      after post-thaw washing (n = 84) or bedside thawing (n = 83). RESULTS: No life
      threatening infusion-related side effects were reported in either group. There
      was no significant difference in the mean CD34+ cells/kg dose of infused auto
      PBSC in the two groups (p = 0.41), nor in the number of days to neutrophils > 0.5
      * 109/L (p = 0.14), days to platelets > 20 * 109/L (p = 0.64), or days to
      platelets > 50 * 109/L (p = 0.62) after transplant. There was also no difference
      in the number of days on total parenteral nutrition (p = 0.69), days on G-CSF
      therapy (p = 0.48), or days with fever (p = 0.73). Finally, there was no
      significant difference in the number of red cell units transfused (p = 0.32), or
      platelet units transfused (p = 0.94) after the transplant. One-hundred-day
      mortality was identical in the two groups (2.4%). CONCLUSION: Both thawing
      procedures are safe and result in acceptable engraftment and patient outcomes.

PMID- 30300878
TI  - Balance Control during Stance and Gait after Cochlear Implant Surgery.
AB  - BACKGROUND: After cochlear implant (CI) surgery, some patients experience
      vertigo, dizziness and/or deficits in vestibulo-ocular reflexes. However, little
      is known about the effect of CI surgery on balance control. Therefore, we
      examined differences in stance and gait balance control before versus after CI
      surgery. METHODS: Balance control of 30 CI patients (mean age 59, SD 15.4 years),
      receiving a first unilateral CI surgery, was measured preoperatively and
      postoperatively 1 month after the initial implant stimulation (2 months after
      surgery). Trunk sway was measured during 14 stance and gait tests using an
      angular-velocity system mounted at lumbar vertebrae 1-3. RESULTS: For pre- versus
      postoperative comparisons across all 30 patients, a nonsignificant worsening in
      balance control was observed. Significant changes were, however, found within
      subgroups. Patients younger than 60 years of age had a significant worsening of
      an overall balance control index (BCI) after CI surgery (p = 0.008), as did
      patients with a normal BCI preoperatively (p = 0.005). Gait task measures
      comprising the BCI followed a similar pattern, but stance control was unchanged.
      In contrast, patients over 60 years or with a pathological BCI preoperatively
      showed improved tandem walking postoperatively (p = 0.0235). CONCLUSION: Across
      all CI patients, CI surgery has a minor effect on balance control 2 months
      postoperatively. However, for patients younger than 60 years and those with
      normal balance control preoperatively, balance control worsened for gait
      indicating the need for preoperative counseling.

PMID- 30300879
TI  - Prognostic Value of Inflammatory Biomarkers in Gastric Cancer Patients and the
      Construction of a Predictive Model.
AB  - BACKGROUND: It is known that inflammation promotes cancer development. However, a
      few studies have evaluated the prognostic significance of inflammatory biomarkers
      in gastric cancer (GC). METHODS: In this study, 2,334 patients who underwent
      gastrectomy for GC at Fudan University Shanghai Cancer Center between 2003 and
      2007 were retrospectively analyzed, and 1,227 patients were found to be eligible.
      The preoperative serum neutrophil-to-lymphocyte ratio (NLR), platelet-to
      lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), and albumin/globulin ratio
      (AGR) levels were analyzed. A nomogram was constructed with the Cox proportional
      hazards regression model in the training set (n = 818) to predict the probability
      of overall survival (OS) and disease-free survival (DFS). The predictive accuracy
      and discriminative ability were determined using the concordance index (C-index)
      and calibration curve. RESULTS: We found that lower AGR and LMR values were
      correlated with decreased OS, lower LMR values, and higher NLR values with a
      decreased DFS. Other significant factors were included to construct the nomogram.
      The discriminative ability of the nomogram was higher than that of the eighth
      American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system
      (0.746 for TNM v.s. 0.654 for the nomogram, p < 0.001). CONCLUSIONS: The nomogram
      yielded a more accurate prognostic prediction in GC patients after gastrectomy,
      suggesting great clinical value.

PMID- 30300880
TI  - Association between Type of Residence and Clinical Signs of Neglect in Older
      Adults.
AB  - BACKGROUND: Studies have demonstrated that measures of lower quality of care and
      associated adverse health effects are more prevalent in for-profit nursing homes
      compared to not-for-profit facilities. However, these studies omit persons who
      receive care in the community setting, and exclusively focus on isolated clinical
      signs that may obscure the true effect size, since these clinical signs rarely
      occur in isolation. OBJECTIVE: In this study, we use the Clinical Signs of
      Neglect Scale (CSNS), which is an aggregate measure of clinical signs of neglect
      and substandard care, to evaluate the association of residence type on health
      outcomes among individuals living in both private community residences and for
      profit and not-for-profit long-term care facilities. METHODS: In a multicenter,
      retrospective data analysis of 1,149 patients identified from an inpatient
      hospital registry, we assessed the relationship between residence type (community
      dwelling, not-for-profit, and for-profit facilities) and clinical signs of
      neglect. Adjusted parameter estimates and 95% CIs were estimated with linear
      regression in 3 models using different reference groups. RESULTS: The most
      serious clinical signs were consistently more prevalent among residents of for
      profit facilities, as were measures of poor institutional quality. Relative to
      low-functioning community-dwelling patients, the mean difference in CSNS scores
      was higher among patients residing in not-for-profit facilities by 1.99 (p =
      0.012) and 3.55 (p <= 0.001) among patients in for-profit facilities. In a
      separate model, the mean difference in CSNS scores among patients living in for
      profit facilities compared to not-for-profit facilities was 1.90 (p = 0.035).
      CONCLUSIONS: Using an aggregate measure, our findings support prior studies
      demonstrating an association between residence type and adverse health outcomes
      for disabled elderly.

PMID- 30300881
TI  - Ecthyma Gangrenosum in Paroxysmal Nocturnal Hemoglobinuria.

PMID- 30300882
TI  - Cortical Processing of Frequency Changes Reflected by the Acoustic Change Complex
      in Adult Cochlear Implant Users.
AB  - The purpose of this study was to examine neural substrates of frequency change
      detection in cochlear implant (CI) recipients using the acoustic change complex
      (ACC), a type of cortical auditory evoked potential elicited by acoustic changes
      in an ongoing stimulus. A psychoacoustic test and electroencephalographic
      recording were administered in 12 postlingually deafened adult CI users. The
      stimuli were pure tones containing different magnitudes of upward frequency
      changes. Results showed that the frequency change detection threshold (FCDT) was
      3.79% in the CI users, with a large variability. The ACC N1' latency was
      significantly correlated with the FCDT and the clinically collected speech
      perception score. The results suggested that the ACC evoked by frequency changes
      can serve as a useful objective tool in assessing frequency change detection
      capability and predicting speech perception performance in CI users.

PMID- 30300883
TI  - Bone Involvement in Hodgkin's Lymphoma: Clinical Features and Outcome.
AB  - Hodgkin's lymphoma (HL) is now a highly curable disease, with an improving 5-year
      survival rate that has now reached 86%. At the time of presentation, HL is
      usually almost entirely confined to the lymph nodes. We performed a retrospective
      single-institution study of 384 cases with a median follow-up of 44 months, with
      the aim of identifying clinical and radiological characteristics and outcomes of
      patients with bone HL; 32 patients (8%) had primary bone involvement, always with
      concurrent nodal disease. These included 22 men (69%) and 10 women (31%) with the
      median age as 41 years. Advanced stages and nodular sclerosis histology prevailed
      among the subgroup. Radiographic features of bone HL are not specific but
      indicate a destructive malignant process with osteosclerosis and/or osteolysis.
      With current chemotherapeutic regimens, the long-term prognosis of patients with
      osseous HL appears good. The presence of bone lesions in HL should not be
      interpreted as implying a worse prognosis than without bone involvement.

PMID- 30300884
TI  - Na+/H+ Exchangers Are Required for the Development and Function of Vertebrate
      Mucociliary Epithelia.
AB  - Na+/H+ exchangers (NHEs) represent a highly conserved family of ion transporters
      that regulate pH homeostasis. NHEs as well as other proton transporters were
      previously linked to the regulation of the Wnt signaling pathway, cell polarity
      signaling, and mucociliary function. Furthermore, mutations in the gene SLC9A3
      (encoding NHE3) were detected as additional risk factors for airway infections in
      cystic fibrosis patients. Here, we used the Xenopus embryonic mucociliary
      epidermis as well as human airway epithelial cells (HAECs) as models to
      investigate the functional roles of NHEs in mucociliary development and
      regeneration. In Xenopus embryos, NHEs 1-3 were expressed during epidermal
      development, and loss of NHE function impaired mucociliary clearance in tadpoles.
      Clearance defects were caused by reduced cilia formation, disrupted alignment of
      basal bodies in multiciliated cells (MCCs), and dysregulated mucociliary gene
      expression. These data also suggested that NHEs may contribute to the activation
      of Wnt signaling in mucociliary epithelia. In HAECs, pharmacological inhibition
      of NHE function also caused defective ciliation and regeneration in airway MCCs.
      Collectively, our data revealed a requirement for NHEs in vertebrate mucociliary
      epithelia and linked NHE activity to cilia formation and function in
      differentiating MCCs. Our results provide an entry point for the understanding of
      the contribution of NHEs to signaling, development, and pathogenesis in the human
      respiratory tract.

PMID- 30300885
TI  - Prognostic Accuracy of Heart Rate Variability Analysis in Neonatal
      Encephalopathy: A Systematic Review.
AB  - BACKGROUND: Heart rate variability analysis offers real-time quantification of
      autonomic disturbance after perinatal asphyxia, and may therefore aid in disease
      stratification and prognostication after neonatal encephalopathy (NE). OBJECTIVE:
      To systematically review the existing literature on the accuracy of early heart
      rate variability (HRV) to predict brain injury and adverse neurodevelopmental
      outcomes after NE. DESIGN/METHODS: We systematically searched the literature
      published between May 1947 and May 2018. We included all prospective and
      retrospective studies reporting HRV metrics, within the first 7 days of life in
      babies with NE, and its association with adverse outcomes (defined as evidence of
      brain injury on magnetic resonance imaging and/or abnormal neurodevelopment at
      >=1 year of age). We extracted raw data wherever possible to calculate the
      prognostic indices with confidence intervals. RESULTS: We retrieved 379
      citations, 5 of which met the criteria. One further study was excluded as it
      analysed an already-included cohort. The 4 studies provided data on 205 babies,
      80 (39%) of whom had adverse outcomes. Prognostic accuracy was reported for 12
      different HRV metrics and the area under the curve (AUC) varied between 0.79 and
      0.94. The best performing metric reported in the included studies was the
      relative power of high-frequency band, with an AUC of 0.94. CONCLUSIONS: HRV
      metrics are a promising bedside tool for early prediction of brain injury and
      neurodevelopmental outcome in babies with NE. Due to the small number of studies
      available, their heterogeneity and methodological limitations, further research
      is needed to refine this tool so that it can be used in clinical practice.

PMID- 30300886
TI  - Different Genetic Expression Profiles of Oxidative Stress and Apoptosis-Related
      Genes in Crohn's Disease.
AB  - BACKGROUND/AIMS: Increased oxidative stress and decreased immune cell apoptosis
      have been reported to be important factors in the pathogenesis of Crohn's disease
      (CD). Our aim was to characterize the genetic expression of molecules implicated
      in the regulation of oxidative stress and apoptosis in peripheral white
      mononuclear cells of 18 healthy volunteers (controls) and 20 patients at the
      onset of CD (active CD [aCD]): 10 who achieved remission (inactive CD [iCD]) and
      10 who did not present a complete and deep response to treatment (aCD-T).
      METHODS: mRNA expression was measured by the Agena MassARRAY quantitative gene
      expression analysis application. The genes analyzed were Fas-receptor (FASR), Fas
      ligand (FASL), signal transducer and activator of transcription 1 (STAT1),
      nuclear factor kappa-light-chain--enhancer of activated B cells (NFKB1),
      apoptosis signal-regulating kinase 1 (ASK1), serine/threonine-protein kinase H1
      (PSKH1), ATP-binding cassette sub-family B1 (ABCB1) and peptidylprolyl isomerase
      D (PPID). RESULTS: During a CD flare, we found specific upregulated expression of
      the genes STAT1 and PSKH1, whereas ABCB1 and FASL were downregulated. In the
      patients with iCD, FASR and NFKB1 were upregulated. The expression levels of
      NFKB1, STAT1 and ABCB1 did not show any difference in patients with aCD at the
      onset of the disease and after treatment (aCD-T). The expression levels of PPID
      and ASK1 did not show any differences in the patients with aCD, iCD and the
      controls. We have also reviewed the cellular function and role of these genes in
      CD. CONCLUSIONS: These findings contribute to improving the understanding of the
      pathogenesis of CD and highlight potential genes involved.

PMID- 30300887
TI  - Hyperbaric Oxygen Therapy as Concurrent Treatment with Systemic Steroids for
      Idiopathic Sudden Sensorineural Hearing Loss: A Comparison of Three Different
      Steroid Treatments.
AB  - We analyzed 356 patients with idiopathic sudden sensorineural hearing loss
      treated with hyperbaric oxygen therapy and systemic steroids (n = 161), systemic
      steroids alone (n = 160), or intratympanic and systemic steroids (n = 35). The
      main outcome measure was the hearing recovery rate. The effect of other
      variables, including the initial averaged 5-frequency hearing level, patient age,
      interval between the onset of symptoms and treatment, presence of vertigo as a
      complication, presence of diabetes mellitus, smoking history, and presence of
      hypertension, on the hearing recovery rate was also evaluated. The overall
      hearing recovery rate was significantly higher for the patients treated with
      hyperbaric oxygen therapy and systemic steroids than for those treated with
      systemic steroids alone (p < 0.001) or systemic and intratympanic steroids (p <
      0.001). The presence of vertigo negatively affected hearing recovery. Our
      findings suggest that hyperbaric oxygen therapy confers a significant additional
      therapeutic benefit when used in combination with steroid therapy for idiopathic
      sudden sensorineural hearing loss.

PMID- 30300888
TI  - [Arzneipflanzen im Berner Pferdestall: Erfahrungswissen von Pferdehaltern].
AB  - Hintergrund: Wahrend uber den traditionellen Einsatz von Arzneipflanzen durch
      Landwirtinnen und Landwirte beim Nutztier sowohl in Sudeuropa als auch in der
      Schweiz zunehmend wissenschaftliche Veroffentlichungen vorliegen, fehlen gezielte
      Studien mit Pferdebesitzern weitestgehend. Mit der vorliegenden Studie sollte
      dieses Wissen exemplarisch fur den Schweizer Kanton Bern erfasst werden.
      Probanden und Methoden: Methodisch an vorhergehende Studien in der Schweiz
      angelehnt, wurden von 2011-2012 7 Pferdehalter im Alter von 24-65 Jahren anhand
      eines semistrukturierten Fragebogens zum Einsatz von Arzneipflanzen bei ihren
      Pferden interviewt. Neben Informationen zu Pflanzenarten und Pflanzenteilen
      wurden die Zubereitung und Anwendung (inklusive Dosierung) der Rezepturen
      detailliert dokumentiert. Ergebnisse: Insgesamt wurden 21 Rezepturen von den
      Berner Pferdehaltern genannt, von denen 4 Mischungen aus 2-5 verschiedenen
      Pflanzenarten waren. In den Rezepturen wurden 27 Pflanzenarten aus 22
      Pflanzenfamilien verwendet. Fur mehr als 50% der Rezepte wurden die
      Arzneipflanzen in der Apotheke gekauft, jedoch lediglich fur 1 (4%) beim
      Tierarzt; fur ein weiteres Drittel der Rezepte wurden Pflanzen gesammelt. Fur die
      21 Rezepturen wurden 30 Anwendungen beschrieben, vor allem zur Behandlung der
      Haut, des Bewegungsapparats und der Atemwege. Am haufigsten wurden Anwendungen
      von Ingwer (Zingiber officinale) und Johanniskraut (Hypericum perforatum)
      genannt. Beide Pflanzen werden uberwiegend zur innerlichen (Ingwer) bzw.
      aubetaerlichen Behandlung (Johanniskrautblutenol) von Erkrankungen des
      Bewegungsapparats eingesetzt. Schlussfolgerungen: Gemessen an der Zahl der
      interviewten Pferdehalter kommt im Kanton Bern traditionell ein breites Spektrum
      von Arzneipflanzen beim Pferd zum Einsatz. Auch wenn Tierarzte aktuell kaum als
      Bezugsquelle fur Arzneipflanzen dienen, durfte das Potenzial fur die
      tierarztliche Phytotherapie in der Pferdemedizin grobeta sein.

PMID- 30300889
TI  - One-Year Experience of Implementation of 100% Cervical Cytology Rapid Review.

PMID- 30300890
TI  - Can Fetal Umbilical Venous Blood Be a Reliable Source for Admission Complete
      Blood Count and Culture in NICU Patients?
AB  - BACKGROUND: Minimizing initial neonatal blood draws and their associated pain is
      important. The placenta has ample fetal blood that is otherwise discarded;
      obtaining admission laboratory evaluations from fetal umbilical venous blood
      (FUVB) may provide a suitable alternative. OBJECTIVE: We hypothesized that
      obtaining an aerobic bacterial blood culture (BCX) and a complete blood count
      with manual differential (CBC/diff) from FUVB is feasible and yields results
      comparable to those obtained directly from the neonate. STUDY DESIGN: BCX and
      CBC/diff were attempted on paired samples from FUVB (in the delivery room) and
      neonatal blood (shortly after NICU admission) of 110 patients. The paired t test,
      Pearson's correlation coefficient (R), and multivariable linear regression were
      used for data analysis. RESULTS: Positive BCXs were found in 9 of 108 FUVB
      samples compared to 1 of 91 neonatal samples. Three out of 9 FUVB cultures were
      true pathogens, including 2 Escherichia coli and 1 viridans group streptococcus,
      all with negative corresponding paired neonatal cultures. There was 1 positive
      neonatal BCX, E. coli, with a negative paired FUVB culture. Neonatal hemoglobin
      (Hb), platelets (PLT), and white blood cells (WBC) all significantly (p < 0.0001)
      correlated with the paired FUVB samples (R = 0.50, 0.49, and 0.84, respectively).
      Hb, PLT, and WBC values were clinically comparable but statistically higher in
      neonatal blood (the differences were 2.3 g/dL, 30,000 cells/MUL, and 2,800
      cells/MUL, respectively; p < 0.007 for all comparisons). CONCLUSIONS: FUVB is
      suitable for obtaining CBC/diff. FUVB is an appropriate second source for BCX as
      it yields additional true pathogens. Our findings may support the presence of
      "culture-negative sepsis" in some neonates.

PMID- 30300891
TI  - Advances and Current Challenges Associated with the Use of Human Induced
      Pluripotent Stem Cells in Modeling Neurodegenerative Disease.
AB  - One of the most profound advances in the last decade of biomedical research has
      been the development of human induced pluripotent stem cell (hiPSC) models for
      identification of disease mechanisms and drug discovery. Human iPSC technology
      has the capacity to revolutionize healthcare and the realization of personalized
      medicine, but differentiated tissues derived from stem cells come with major
      criticisms compared to native tissue, including variability in genetic
      backgrounds, a lack of functional maturity, and differences in epigenetic
      profiles. It is widely believed that increasing complexity will lead to improved
      clinical relevance, so methods are being developed that go from a single cell
      type to various levels of 2-D coculturing and 3-D organoids. As this inevitable
      trend continues, it will be essential to thoroughly understand the strengths and
      weaknesses of more complex models and to develop criteria for assessing
      biological relevance. We believe the payoff of robust, high-throughput,
      clinically meaningful human stem cell models could be the elimination of often
      inadequate animal models. To facilitate this transition, we will look at the
      challenges and strategies of complex model development through the lens of
      neurodegeneration to encapsulate where the disease-in-a-dish field currently is
      and where it needs to go to improve.

PMID- 30300892
TI  - Determination of Cardiac Output: A Game of Thrones.

PMID- 30300893
TI  - ACTA2 Cerebral Arteriopathy: Not Just a Puff of Smoke.
AB  - BACKGROUND: Missense mutations in the gene that codes for smooth muscle actin,
      ACTA2, cause diffuse smooth muscle dysfunction and a distinct cerebral
      arteriopathy collectively known as multisystemic smooth muscle dysfunction
      syndrome (MSMDS). Until recently, ACTA2 cerebral arteriopathy was considered to
      be a variant of moyamoya disease. However, recent basic science and clinical data
      have demonstrated that the cerebral arteriopathy caused by mutant ACTA2 exhibits
      genetic loci, histopathology, neurological sequelae, and radiographic findings
      unique from moyamoya disease. We conducted a literature review to provide insight
      into the history, clinical significance, and neurosurgical management of this
      recently described novel cerebral arteriopathy. SUMMARY: We performed a
      literature search using PubMed with the key words "ACTA2 mutation," "ACTA2
      cerebral arteriopathy," and "multisystemic smooth muscle dysfunction syndrome."
      Case reports with confirmed ACTA2 mutations and cerebral arteriopathy were
      included in our review. Our literature search revealed 15 articles (58 cases) of
      confirmed ACTA2 cerebral arteriopathy. Distinctive features of this arteriopathy
      included an aberrant internal carotid circulation with dilatation of the proximal
      segments, occlusive disease at the distal segments, and dolichoectasia. As such,
      mutant ACTA2 predisposed patients to ischemic strokes as children. Direct and
      indirect cerebral revascularization procedures are the mainstay treatment options
      with varying degrees of success. Key Messages: ACTA2 cerebral arteriopathy is a
      recently described novel cerebrovascular disease seen in patients with MSMDS.
      Patients currently diagnosed with moyamoya disease who also have dysfunction of
      smooth muscle organs may benefit from reevaluation by a medical geneticist and
      ACTA2 genotyping.

PMID- 30300894
TI  - Favorable Outcomes of Elderly ABO-Incompatible Kidney Transplantation-Pilot
      Single Center Experience.
AB  - BACKGROUND: The growth in the end-stage kidney disease (ESKD) population has been
      predominantly in the older adult population. In Japan, ABO-incompatible kidney
      transplantation has become an acceptable treatment option. However, few studies
      have been conducted on elderly ABO-incompatible kidney transplantation. PATIENTS
      AND METHODS: Seventeen patients aged 60 years and older who received their grafts
      from ABO-incompatible living donors at our institution between December 2006 and
      September 2016 were enrolled in this study, and the outcome of these recipients
      was evaluated. RESULTS: All 17 patients underwent successful kidney
      transplantation. Both overall patient and graft survival rates were 100, 100, and
      83.3% at posttransplant 1, 3, and 5 years respectively. Six of the 17 patients
      (35.3%) had an episode of biopsy-proven acute cellular rejection. Two patients
      who developed steroid- and deoxyspergualin-resistant acute rejection required
      anti-human thymocyte immunoglobulin. CONCLUSION: ABO-incompatible kidney
      transplantation may be an effective radical renal replacement therapy for elderly
      patients with ESKD, although it could be a high-risk procedure.

PMID- 30300895
TI  - The Relationship between the Fetal Volume-Corrected Renal Artery Pulsatility
      Index and Amniotic Fluid Volume.
AB  - INTRODUCTION: To evaluate if the volume-corrected renal artery pulsatility index
      (vcRA-PI) is more closely related to the amniotic fluid level than the
      uncorrected or the gestational age (GA)-adjusted RA-PI. METHODS: RA-PI and kidney
      volume were measured in low- and high-risk pregnancies at 17-38 weeks. Fetal
      anomalies associated with nonrenal causes of abnormal amniotic fluid volume were
      excluded. The vcRA-PI was calculated by dividing the RA-PI by the renal volume.
      The RA-PI was adjusted for GA, to obtain the GA-adjusted RA-PI. The uncorrected,
      GA-adjusted, and the vcRA-PI were related to the amniotic fluid level using
      nonparametric tests and receiver operating characteristic (ROC) curve analyses.
      RESULTS: 146 examinations from 59 pregnancies were reviewed. Of these, 16 had
      oligo- and 15 had polyhydramnios. A higher vcRA-PI was associated with
      oligohydramnios (OR 2.54, 95% CI 1.67-3.86, p < 0.001), while the uncorrected RA
      PI and GA-adjusted RA-PI were not able to predict oligohydramnios. ROC curve
      analysis showed a high predictive accuracy of the vcRA-PI for oligohydramnios
      (AUC 0.84, 95% CI 0.72-0.94). On the other hand, the uncorrected RA-PI and GA
      adjusted RA-PI significantly predicted polyhydramnios (p = 0.04 and 0.02,
      respectively), while the vcRA-PI did not. CONCLUSION: The vcRA-PI is superior to
      the uncorrected and the GA-adjusted RA-PI in predicting oligohydramnios.

PMID- 30300896
TI  - An Analysis of the Association between Epilepsy-Related Genes and Vertigo in the
      Polish Population.
AB  - Considering the possibility of a common genetic background of vertigo and
      epilepsy, we genotyped an affected group of individuals with vertigo and an
      unaffected group, by studying 26 single-nucleotide polymorphisms (SNPs) in 14
      genes which were previously reported to be of particular importance for epilepsy.
      Significant differences were found between the patients and the control group
      (chi2 = 38.3, df = 3, p = 1.6 * 10-7) for the frequencies of haplotypes consist
      ing of 2 SNPs located in chromosome 11 (rs1939012 and rs1783901 within genes MMP8
      and SCN3B, respectively). The haplotype rs1939012:C-rs1783901:A, consisting of
      the minor-frequency alleles was found to be associated with a higher risk of
      vertigo (OR = 5.0143, 95% CI = 1.6991-14.7980, p = 0.0035). In contrast, the
      haplotype rs1939012:T-rs1783901:A showed a significant association with a
      decreased risk of the disease (OR = 0.0597, 95% CI = 0.0136-0.2620, p = 0.0002).
      Our results suggest that the SNPs rs1939012 and rs1783901 may play a potential
      role of gene regulation and/or epistasis in a complex etiology of vertigo.

PMID- 30300897
TI  - COMPETITIVE TESTING THE WHO 2010 VS THE WHO 2017 GRADING OF PANCREAS
      NEUROENDOCRINE NEOPLASIA: DATA FROM A LARGE INTERNATIONAL COHORT STUDY.
AB  - : <br>Background: the World Health Organization (WHO) and the American Joint
      Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine
      neoplasms from a three-tiers (WHO-AJCC 2010) to a four-tiers system by
      introducing the novel category of NET G3 (WHO-AJCC 2017). OBJECTIVES: This study
      aims at validating the WHO-AJCC 2017 and identifying the most effective grading
      system. METHOD: 2102 patients were enrolled; entry criteria were i) performed
      surgery; ii) at least two years of follow-up; iii) observation time up to 2015.
      Data from 34 variables were collected; grading was assessed and compared for
      efficacy by statistical means including Kaplan Meier method, Cox regression
      analysis, Harrell's C statistics and Royston's explained variation in univariable
      and multivariable analyses. RESULTS: At descriptive analysis, the two grading
      systems demonstrated statistically significant differences for the major category
      sex but not for age groups. At Cox regression analysis, both grading systems
      showed statistically significant differences between grades for OS and EFS,
      however no statistically significant difference was observed between the two G3
      classes of WHO-AJCC 2017. At multivariable analysis for the two models fitted to
      compare efficacy, the two grading systems performed equally well with
      substantially similar optimal discrimination and well-explained variation for
      both OS and EFS. The WHO-AJCC 2017 grading system retained statistically
      significant difference between the two G3 classes for OS but not for EFS.
      CONCLUSIONS: the WHO-AJCC 2017 grading is at least equally performing as the WHO
      AJCC 2010 but allows the successful identification of the most aggressive PanNET
      subgroup. Grading is confirmed as probably the most powerful tool for patient
      survival prediction. <br>.

PMID- 30300898
TI  - Endovascular Clot Retrieval by Hub-and-Spoke Service Delivery is Feasible
      Compared with Direct-to-Mothership.
AB  - BACKGROUND: Endovascular clot retrieval (ECR) improves outcomes for acute
      ischaemic stroke with large artery occlusion. However, the provision of ECR
      requires resource-intensive comprehensive stroke centres (CSC), which are
      impractical to establish in regional hospitals. An alternative is a "hub-and
      spoke" model, whereby ischaemic strokes are triaged at the regional primary
      centres and where eligible, transferred to a CSC. We aimed to compare the
      outcomes of patients directly admitted to a CSC with patients treated in the "hub
      and-spoke" model. We hypothesize that there are no significant differences in
      clinical outcomes between the 2 systems. METHODS: We included patients undergoing
      ECR at a CSC. Patients were categorised into 2 groups; the first group included
      patients directly admitted to the CSC and the second group included patients in
      the "hub-and-spoke" model. Good clinical outcome was defined as modified Rankin
      Scale 0-2 and the difference between the 2 groups was tested by logistic
      regression. RESULTS: Of 178 patients, 50 (28%) presented directly to CSC and 128
      (72%) were transferred from a referring hospital. The median age was 70
      (interquartile range 58-77) and 61% were male. Thrombolysis in ischaemic cerebral
      infarction 2b/3 recanalisation was achieved in 79% of patients. Of the direct
      group, 63% (95% CI 48-77%) achieved good clinical outcomes compared to 52% (95%
      CI 43-61%) in the "hub-and-spoke" group (p = 0.233). CONCLUSION: This state-wide
      service model demonstrates comparable clinical outcomes to that described in
      clinical trials. We found no significant difference in outcome between patients
      directly admitted to CSC and those with "hub-and-spoke" service delivery.

PMID- 30300899
TI  - IgD Myeloma: Dialysis-Independence following High-Dose Melphalan and Autologous
      Stem Cell Transplantation.

PMID- 30300900
TI  - Open Fetal Surgery in Turkey.

PMID- 30300901
TI  - Id1/NR2B Receptor Pathway Regulates Rat Cochlear Sensory Epithelial Cell Survival
      after Radiation.
AB  - Survival of cochlear sensory epithelial cells may be regulated by inhibitor of
      differentiation-1 (Id1) and the N-methyl-D-aspartic acid (NMDA) receptor.
      However, it is unclear whether Id1 and the NMDA receptor are involved in the
      radiation-mediated survival of rat cochlear sensory epithelial cells. Here, we
      show that the percentage of apoptotic cells increased, the percentage of cells in
      the S phase decreased, Id1 mRNA and protein expression decreased and the NMDA
      receptor subtype 2B (NR2B) mRNA and protein level increased in OC1 cells after
      radiation. Cells infected with the Id1 gene exhibited higher Id1 mRNA and protein
      levels and lower NR2B mRNA and protein levels than the control cells. In
      contrast, after transfection of the Id1 siRNA into OC1 cells, Id1 mRNA and
      protein expression decreased and NR2B mRNA and protein expression increased
      relative to that of the control group. Additionally, treatment with ifenprodil
      for 24 h before radiation reduced apoptosis and increased the percentage of cells
      in the S phase. Our results suggest that Id1 and NR2B might regulate the survival
      of OC1 cells following radiation.

PMID- 30300902
TI  - Lung Biopsy in Interstitial Lung Diseases: There Is More than One Way to Cook an
      Egg.

PMID- 30300903
TI  - Endothelial Function in Patients with Severe and Moderate Haemophilia A and B.
AB  - The life expectancy of patients with haemophilia has increased and therefore the
      interest in age-related comorbidities has grown. The aim of this study was to
      determine whether haemophilia patients have a different endothelial function
      compared with the general population. A total of 26 patients with severe or
      moderate haemophilia A or B, 14 controls and 36 patients with coronary artery
      disease (CAD) were included in this study. Five markers of endothelial
      dysfunction (MOEDs) were determined. Moreover, the endothelial function was
      examined using the Itamar Endo-PAT, and the reactive hyperemia index (RHI) was
      calculated from the results. The MOEDs soluble intercellular adhesion molecule-1
      (p = 0.0095) and interleukin-6 (p = 0.010) were significantly higher for patients
      with haemophilia compared with the control group. The presence of increased
      adhesion molecule levels and low-grade inflammation is suggestive of a decreased
      endothelial function. RHI is impaired in CAD patients (1.862), whereas
      haemophilia patients have an RHI of 1.958 in comparison with 2.112 in controls (p
      = 0.127). Therefore, laboratory and functional measurements imply a possible
      higher risk for CAD in haemophilia patients.

PMID- 30300904
TI  - Impact of Prosthesis-Patient Mismatch on Survival after Mitral Valve Replacement:
      A Meta-analysis.
AB  - BACKGROUND:  Numerous studies have demonstrated a negative impact of prosthesis
      patient mismatch (PPM) on long-term clinical outcomes after aortic valve
      replacement. However, the impact of PPM after mitral valve replacement (MVR) on
      clinical outcomes is still controversial. This study was conducted to evaluate
      the impact of PPM on early and long-term survival after MVR. METHODS:  A
      literature search of five databases was performed. The primary and secondary
      outcomes were all-cause mortality and early mortality, respectively. Subgroup
      analyses were performed according to the risk of bias, patients' age, proportion
      of female patients, and proportion of patients with mechanical MVR. RESULTS: 
      Eleven nonrandomized studies including 8,072 patients were included in this meta
      analysis. The overall incidence of PPM was 58.0% (range: 10.4-85.9%). The odds
      ratio of early mortality in nine studies was not significantly different between
      the PPM and non-PPM patients (odds ratio: 1.35; 95% confidence interval [CI]:
      0.98-1.86). A pooled analysis in 11 studies demonstrated that all-cause mortality
      after MVR was higher in the PPM than non-PPM patients (hazard ratio [HR]: 1.39;
      95% CI: 1.09-1.77). This analysis revealed a moderate to high heterogeneity (I 2
      = 69.4%). When pooled analyses were performed in two subgroups according to the
      proportion of patients with mechanical MVR, there were low heterogeneity in each
      group. No other subgroup analyses demonstrated a significant difference in the HR
      of all-cause mortality. Funnel plots and Egger's tests showed no visually and
      statistically significant publication bias. CONCLUSION:  The present meta
      analysis indicates that PPM negatively affects long-term survival after MVR.

PMID- 30300905
TI  - Icariin Improves Functional Behavior in a Mouse Model of Traumatic Brain Injury
      and Promotes Synaptic Plasticity Markers.
AB  - Epimedii Herba (EH) has been used in traditional Asian medicine to treat
      hemiplegia following stroke. Icariin, its major active component, is used as a
      quality-control marker and for its various pharmacological effects. We
      hypothesized that icariin would show protective effects following traumatic brain
      injury (TBI). The TBI mouse model was induced using a controlled cortical impact
      method. Body weight, brain damage, motor function, and cognitive function were
      evaluated. Synaptogenesis markers were analyzed to investigate potential
      mechanisms of action. The animals were divided into six groups: sham, control,
      minocycline-treated group, and icariin-treated (3, 10, and 30 mg/kg, p. o.)
      groups. The icariin 30 mg/kg-treated group regained body weight at 7 and 8 d post
      TBI. Icariin 30 mg/kg- and 10 mg/kg-treated groups showed enhanced sensory-motor
      function at 8 d post TBI in rotarod and balance beam tests. Icariin-treated
      groups showed increased recognition index in the novel object recognition test at
      all doses and increased spontaneous alternation in the Y-maze test at 30 mg/kg.
      Icariin upregulated brain-derived neurotrophic factor, synaptophysin and
      postsynaptic density protein 95 expressions. However, no protective effects
      against brain damage or neuronal death were observed. The current results provide
      a basis for using icariin following TBI and suggest that it could be a candidate
      for the development of therapeutic agents for functional recovery after TBI.

PMID- 30300906
TI  - How Much Should I Record During a CEUS Examination? Practical Aspects of the
      "Real-Time" Feature of a Contrast Ultrasound Study.

PMID- 30300907
TI  - Diagnostic Value of Contrast-Enhanced Ultrasound in a 12-Year-Old Girl with
      Suspected Malposition of a Bladder Catheter and Ambiguous Findings on B-Mode
      Ultrasound - A Case Report.

PMID- 30300908
TI  - [Congress Report of the Ultraschall-Dreilandertreffen 2017 - Summary - Abdomen
      Sonography and CEUS].

PMID- 30300909
TI  - Genetic Depletion of Thromboxane A2/Thromboxane-Prostanoid Receptor Signalling
      Prevents Microvascular Dysfunction in Ischaemia/Reperfusion Injury.
AB  - OBJECTIVE:  Activation of thromboxane A2 synthase (TXAS)/thromboxane A2
      (TXA2)/thromboxane prostanoid (TP) receptor leads to arterial constriction,
      platelet aggregation and vascular injury. We attempted to characterize the
      microvascular dysfunction in ischaemia/reperfusion injury using genetically
      modified TXAS-/-, TP-/- and TXAS-/-TP-/- mice. APPROACH AND RESULTS:  The cardiac
      micro-circulation and electrocardiograms were evaluated from B6, TXAS-/-, TP-/-
      and TXAS-/-TP-/- mice in response to intravenous saline, endothelin-1, U46619 (a
      TXA2 agonist) and myocardial ischaemia/reperfusion injury. Cardiac function was
      investigated with myocardial permeability, the troponin I concentration and the
      infarct size. Myocardial TXAS, TP, endothelial nitric oxide (NO) synthase (eNOS),
      nicotinamide adenine dinucleotide phosphate oxidase 4 (NOx4), 4-hydroxynonenal,
      interleukin (IL)-1beta, cell apoptosis, coronary effluent thromboxane B2 (TXB2)
      and superoxide anions (O2 -) and NO concentrations were measured. Mice mesenteric
      reactivity in response to various drugs was assessed by wire myography. In vivo
      fluorescent platelet adhesiveness to the mesenteric arterial endothelium after
      FeCl3 stimulation was examined. In B6 mice, ischaemia/reperfusion significantly
      increased levels of ST-segment elevation, myocardial TXAS, TP, NOx4, IL-1beta,
      apoptosis, coronary endothelin-1, TXB2, O2 - release and the infarct size, with
      concomitant decreases in eNOS, NO concentrations and cardiac micro-circulation.
      These effects were remarkably depressed in TXAS-/-, TP-/- and TXAS-/-TP-/- mice.
      Aspirin treatment or depletion of the TXAS, TP or TXAS/TP gene significantly
      attenuated the exaggerated vascular reactivity by vasoconstrictors and
      vasodilators and efficiently reduced platelet adhesion to the mesenteric
      endothelium under FeCl3 stimulation. CONCLUSION:  Inhibiting TXAS/TXA2/TP
      signalling confers microvascular protection against oxidative injury in both
      cardiac and mesenteric arteries.

PMID- 30300910
TI  - Monocytes of Different Subsets in Complexes with Platelets in Patients with
      Myocardial Infarction.
AB  - Acute myocardial infarction (AMI) is associated with activation of various cells,
      including platelets that form monocyte-platelet complexes (MPCs). Here, we
      analysed MPC in vivo and in vitro and investigated the abilities of different
      monocyte subclasses to form MPC, the characteristics of the cells involved in MPC
      formation and MPC changes in AMI. We identified MPC by co-staining for platelet
      antigen CD41a and monocyte antigens CD14 and CD16. Platelet activation was
      evaluated from expression of phosphatidylserine as revealed by annexin V. Our
      results confirm published data and provide new information regarding the patterns
      of MPC in AMI patients. We found that the patterns of platelet aggregation with
      monocytes were different in AMI patients and controls: (1) in AMI patients, MPC
      formed by intermediate monocytes carry more platelets whereas in healthy controls
      more platelets aggregated with classical monocytes; (2) the numbers of MPC in AMI
      patients, being already higher than in controls, were further increased if these
      patients suffered various in-hospital complications; (3) on the basis of the
      CD41a fluorescence of the antibody-stained MPC, some of the aggregates seem to
      consist of monocytes and platelet-derived extracellular vesicles (EVs); (4)
      aggregation of monocytes with platelet EV occurred in in vitro experiments; and
      (5) these experiments demonstrated that monocytes from AMI patients aggregate
      with both platelets and platelet EVs more efficiently than do monocytes from
      controls. MPC in AMI patients may play an important role in this pathology.

PMID- 30300911
TI  - IL-9 Promotes the Development of Deep Venous Thrombosis by Facilitating Platelet
      Function.
AB  - The development of deep venous thrombosis (DVT) is a sterile inflammatory process
      related to cytokines, such as interleukin (IL)-6 or IL-17. IL-9 is a cytokine
      involved in many inflammatory diseases, including cystic fibrosis, ulcerative
      colitis, psoriasis and psoriatic arthritis. However, it remains unknown whether
      IL-9 is related to DVT. In this study, we characterized the role and mechanism of
      IL-9 in DVT. Analysis of the data of patients with and without DVT revealed that
      stasis, venous surgery as well as elevated IL-9 and sP-selectin levels were
      related to the development of DVT. We also showed for the first time that IL-9
      receptor was expressed in mouse platelets, and it dramatically promoted the
      aggregation rate and expression of P-selectin (CD62P) in the presence of
      adenosine diphosphate, but otherwise exhibited no effect on platelets. This study
      also revealed that Janus kinase 2/signal transducer and activator of
      transcription 3 (JAK2/STAT3) signalling pathway, not phosphoinositide 3
      kinase/AKT pathway, was involved in the process. We also showed in a mouse model
      of stasis that the thrombus size (weight and length) and CD62P expression in the
      thrombus were higher and lower in the IL-9 group and IL-9 antibody group,
      respectively, than in the control group. All these findings indicated that IL-9
      facilitated platelet function through the JAK2/STAT3 pathway, thus promoting the
      development of DVT.

PMID- 30300912
TI  - Spontaneous Septic Arthritis of Canine Elbows: Twenty-One Cases.
AB  - OBJECTIVE:  This study provides information on clinical features, diagnosis,
      treatment and associated risk factors of spontaneous septic elbow arthritis in
      the dog. METHODS: Medical records between March 2007 and June 2015 were searched
      for cases of spontaneous septic elbow arthritis with a diagnosis based on
      clinical signs, arthrocentesis, cytological and microbiological analysis of elbow
      joint synovial fluid, radiography and outcome following treatment. RESULTS:
      Twenty-one cases of septic arthritis were identified. Pre-existing osteoarthritis
      was present in 14/15 elbows for which diagnostic imaging was available. Although
      all cases had increased neutrophil count on synovial fluid cytology, culture was
      only positive in 12/21. Despite initial improvement in lameness scores (pre
      treatment 9/10 [range: 1-10] versus post-treatment 3/10 [range: 1-5]), 11/12 had
      residual long-term lameness. Recurrence of infection was noted in 3/12 elbows for
      which long-term (>8 weeks) follow-up was available. There was an acute mortality
      rate of 2/21 associated with severe systemic sepsis. CLINICAL SIGNIFICANCE:
      Septic arthritis, even in the absence of pyrexia, should be considered as a major
      differential diagnosis in middle aged, large breed dogs, with pre-existing elbow
      arthritis, that suffer an acute onset lameness, with elbow joint effusion and
      discomfort. Antibiotic therapy alone was effective for treatment with high
      initial response rates. Chronic lameness post-treatment was common, and a high
      rate of recurrence was seen with 3/12 dogs suffering more than one episode.

PMID- 30300913
TI  - Sensitivity and Specificity of a Weight Distribution Platform for the Detection
      of Objective Lameness and Orthopaedic Disease.
AB  - INTRODUCTION:  Weight distribution and off-loading at the stance are commonly
      used subjective assessments during the orthopaedic examination. The clinical
      relevance, sensitivity and specificity of limb off-loading have not yet been
      established. The aim of the study was to assess off-loading on a weight
      distribution platform (WDP) and determine the sensitivity and specificity at
      various cut-off points for the detection of objective lameness (OL) and
      orthopaedic disease (OD). MATERIALS AND METHODS:  The total pressure index was
      used to determine OL on a pressure-sensitive walkway (PSW). Normal weight
      distribution on both the PSW and WDP was considered 30/30/20/20. A total pressure
      index standard deviation of 2 was used. The sensitivity and specificity of the
      WDP for the identification of OL and OD was determined at cut-off points 1 to 6
      below normal weight distribution values. RESULTS:  All patients in the study (n =
      50) had confirmed OD. The PSW identified 36/50 (74%) patients as OL; these were
      deemed to be OL for sensitivity and specificity analysis of WDP data. At cut-off
      point 1, the WDP had the highest sensitivity for OD (84%) and OL (97%). At cut
      off point 6, the WDP had the highest specificity for OD (98%) and OL (98%). The
      highest combination of sensitivity and specificity for both OD (1.65) and OL
      (1.80) was at cut-off point 2. DISCUSSION/CONCLUSION:  The WDP provided the
      highest combined sensitivity and specificity at cut-off point 2 below the normal
      value for the detection of both OL and OD.

PMID- 30300914
TI  - Reproducibility, Accuracy and Effect of Autoclave Sterilization on a
      Thermoplastic Three-Dimensional Model Printed by a Desktop Fused Deposition
      Modelling Three-Dimensional Printer.
AB  - OBJECTIVES:  The main purpose of this study was to determine the reproducibility
      and accuracy of a three-dimensional (3D) bone model printed on a desktop 3D
      printer based on fused deposition modelling (FDM) technology with polylactic acid
      (PLA) and the effect of autoclave sterilization on the printed models. METHODS: 
      Computed tomographic images of the tibia were obtained from 10 feline cadavers,
      used to create a bone surface-rendering file and sent to the 3D printing
      software. Right and left tibias were each printed five times with the FDM desktop
      3D printer using PLA plastic material. Plastic models and cadaveric bones were
      measured with a profile projector device at six predetermined landmarks. Plastic
      bones were then sterilized using an autoclave before being re-measured applying
      the same method. Analyses of printed model size reliability were conducted using
      intra-class correlation coefficients (ICC) and Bland-Altman plots. RESULTS:  The
      ICC always showed an almost perfect agreement when comparing 3D-printed models
      issued from the same cadaveric bone. The ICC showed moderate agreement for one
      measurement and strong/perfect agreement for others when comparing a cadaveric
      bone with the corresponding 3D model. Concerning the comparison of the same 3D
      printed model, before and after sterilization, ICC showed either strong or
      perfect agreement. CLINICAL SIGNIFICANCE:  Rapid-prototyping with our FDM desktop
      3D-printer using PLA was an accurate, a reproducible and a sterilization
      compliant way to obtain 3D plastic models.

PMID- 30300915
TI  - Computed Tomographic Trochlear Depth Measurement in Normal Dogs.
AB  - OBJECTIVES:  The main purpose of this study was to describe the relationship
      between patellar maximal craniocaudal thickness and femoral trochlear groove
      depth in normal dogs and to valuate the intra-observer or inter-observer
      variability of maximal trochlear depth and maximal patellar craniocaudal
      thickness using computed tomography. METHODS:  Trochlear groove depth and
      patellar maximal craniocaudal thickness of 40 limbs (20 dogs) were measured by
      three independent veterinarians using three-dimensional multiplanar
      reconstruction computed tomography images. The patellar maximal craniocaudal
      thickness/trochlear depth ratio was determined. RESULTS:  The mean ratio of these
      stifles was 0.46 (range 0.24-0.70), meaning that the mean maximal depth of the
      trochlea was 46% of the mean maximal-patellar thickness. CLINICAL SIGNIFICANCE: 
      A wide range of maximal-patellar-craniocaudal-thickness/maximal trochlear-depth
      ratio was found suggesting that breed studies should be performed to determine a
      breed-specific patellar-thickness/trochlear-depth ratio. To make decisions on
      when and where to perform a sulcoplasty during patellar luxation surgery,
      patella/trochlea thickness relationship should be measured for each breed with
      patellar tracking from stifle hyperflexion to stifle hyperextension.

PMID- 30300916
TI  - Comparison of Early Measurements of the Distraction Index, Norberg Angle on
      Distracted View and the Official Radiographic Evaluation of the Hips of 215 Dogs
      from Two Guide Dog Training Schools.
AB  - OBJECTIVES:  The main purpose of this article is to evaluate the correlation
      between the distraction index (DI) and Norberg angle values in distracted hips
      (distraction Norberg angle, DNA) at 4 months of age and the official hip score
      based on the Federation Cynologique Internationale (FCI) grid at 12 months of
      age. METHODS:  For dogs (n = 215) from two guide dog training organizations, the
      DI and DNA were measured by a single expert on distraction radiographs performed
      at 4 months of age. The FCI score was determined by the same expert at 12 months
      of age on a standard hip-extended view.Statistical analysis included receiver
      operating characteristic curve analysis and concordance correlation coefficient
      calculation. RESULTS:  The mean DI was 0.48, the mean DNA was 86.5 degrees  and
      59.5% of hips had an A FCI score. The concordance correlation coefficient of DI
      and DNA was 0.78. The DI threshold for D- and E-scored hips that was associated
      with the least misclassification was 0.58 (sensitivity [Se] = 0.6, specificity
      [Sp] = 0.82). The DNA threshold that was associated with the least
      misclassification was 85 degrees  (Se = 0.83, Sp = 0.68). CLINICAL SIGNIFICANCE: 
      DNA has a fair correlation with DI at 4 months and reflects hip passive laxity. D
      and E FCI scores at 12 months cannot be reliably predicted from the 4 months
      value of DI or DNA but 96% of hips with DI < 0.58 at 4 months had an A, B or C
      FCI score at 12 months of age. Similarly, 98% of hips with DNA > 85 degrees  at 4
      months had an A, B or C FCI score at 12 months of age.

PMID- 30300917
TI  - Wnt-induced activation of glucose metabolism mediates the in vivo neuroprotective
      roles of Wnt signaling in Alzheimer disease.
AB  - Dysregulated Wnt signaling is linked to major neurodegenerative diseases,
      including Alzheimer disease (AD). In mouse models of AD, activation of the
      canonical Wnt signaling pathway improves learning/memory, but the mechanism for
      this remains unclear. The decline in brain function in AD patients correlates
      with reduced glucose utilization by neurons. Here, we test whether improvements
      in glucose metabolism mediate the neuroprotective effects of Wnt in AD mouse
      model. APPswe/PS1dE9 transgenic mice were used to model AD, Andrographolide or
      Lithium was used to activate Wnt signaling, and cytochalasin B was used to block
      glucose uptake. Cognitive function was assessed by novel object recognition and
      memory flexibility tests. Glucose uptake and the glycolytic rate were determined
      using radiotracer glucose. The activities of key enzymes of glycolysis such as
      hexokinase and phosphofructokinase, Adenosine triphosphate (ATP)/Adenosine
      diphosphate (ADP) levels and the pentose phosphate pathway and activity of
      glucose-6 phosphate dehydrogenase were measured. Wnt activators significantly
      improved brain glucose utilization and cognitive performance in transgenic mice.
      Wnt signaling enhanced glucose metabolism by increasing the expression and/or
      activity of hexokinase, phosphofructokinase and AMP-activated protein kinase.
      Inhibiting glucose uptake partially abolished the beneficial effects of Wnt
      signaling on learning/memory. Wnt activation also enhanced glucose metabolism in
      cortical and hippocampal neurons, as well as brain slices derived from
      APPswe/PS1E9 transgenic mice. Combined, these data provide evidence that the
      neuroprotective effects of Wnt signaling in AD mouse models result, at least in
      part, from Wnt-mediated improvements in neuronal glucose metabolism.

PMID- 30300918
TI  - Hands-Free, Nonwearable Technology for Outpatient Clinic Gait Speed Assessment.

PMID- 30300919
TI  - An application of data mining to identify potential risk factors for anophthalmia
      and microphthalmia.
AB  - BACKGROUND: We examined a large number of variables to generate new hypotheses
      regarding a wider range of risk factors for anophthalmia/microphthalmia using
      data mining. METHODS: Data were from the National Birth Defects Prevention Study,
      a multicentre, case-control study from 10 centres in the United States. There
      were 134 cases of "isolated" and 87 "nonisolated" (with other major birth
      defects) of anophthalmia/microphthalmia and 11 052 nonmalformed controls with
      delivery dates October 1997-December 2011. Using random forest, a data mining
      procedure, we compared the two case types with controls for 201 variables.
      Variables considered important ranked by random forest were included in a
      multivariable logistic regression model to estimate odds ratios and 95%
      confidence intervals. RESULTS: Predictors for isolated cases included paternal
      race/ethnicity, maternal intake of certain nutrients and foods, and childhood
      health problems in relatives. Using regression, inverse associations were
      observed with greater maternal education and with increasing intake of folate and
      potatoes. Odds were slightly higher with greater paternal education, for
      increased intake of carbohydrates and beans, and if relatives had a childhood
      health problem. For nonisolated cases, predictors included paternal
      race/ethnicity, maternal intake of certain nutrients, and smoking in the home the
      month before conception. Odds were higher for Hispanic fathers and smoking in the
      home and NSAID use the month before conception. CONCLUSIONS: Results appear to
      support previously hypothesised risk factors, socio-economic status, NSAID use,
      and inadequate folate intake, and potentially provide new areas such as passive
      smoking pre-pregnancy, and paternal education and ethnicity, to explore for
      further understanding of anophthalmia/microphthalmia.

PMID- 30300920
TI  - Development and Validation of a Fall Prevention Knowledge Test.
AB  - Falls are a serious, persistent problem in hospitals. Ensuring that all hospital
      staff have adequate knowledge of how to prevent falls is the first step in
      prevention. We identified validated fall prevention knowledge tests (FPKTs) and
      planned to conduct a systematic literature review. When the review identified a
      lack of FPKTs, we developed and evaluated a FPKT, confirmed its conceptual
      framework, identified the content domain, drafted test items, devised the format,
      selected items for empirical examination, and conducted a psychometric
      evaluation. We randomly divided a 209-subject data set into test and validation
      samples to make item reduction decisions and examine reliability and validity.
      The typical respondent was a white, 42-year old female nurse with a bachelor's
      degree and 7 years' experience. Subjects were confident in their ability to
      prevent falls, rating themselves an 8 on a self-efficacy scale of 1 (not at all)
      to 10 (very). The 11-item FPKT scale (range 0-11) attained a tetrachoric
      coefficient of 0.73, confirming initial reliability. FPKT mean scores obtained
      before and after fall prevention education improved from 5.1 +/- 1.8 to 6.6 +/-
      1.7. Statistically significant differences (paired t-test = 12.4, p < .001)
      confirmed validity. A robust way to assess nurses' knowledge of fall prevention
      is needed to inform effective educational programs. Addressing gaps in validated
      FPKTs provides an opportunity to inform and evaluate effective fall prevention
      programs.

PMID- 30300921
TI  - "On Water" Surface-initiated Polymerization of Hydrophobic Monomers.
AB  - We present the "on water" surface-initiated Cu-mediated controlled radical
      polymerization ("on water" SI-CuCRP) that converts hydrophobic monomers in
      aqueous reaction medium to polymer brushes at unparalleled speed and efficiency.
      The method allows the facile conversion of a variety of common monomers under
      most simple reaction conditions and with minimal monomer amounts to thick and
      homogeneous polymer brushes. The highly living character of the "on water" SI
      CuCRP allowed the preparation of decablock (homo)polymer brushes and opens the
      pathway to sequentially controlled polymer brushes on solids.

PMID- 30300922
TI  - Influence of OCT1 Ontogeny and Genetic Variation on Morphine Disposition in
      Critically Ill Neonates: Lessons From PBPK Modeling and Clinical Study.
AB  - Morphine is commonly used for analgesia in the neonatal intensive care unit
      (NICU) despite having highly variable pharmacokinetics (PKs) between individual
      patients. The pharmacogenetic (PG) effect of variants at the loci of organic
      cation transporter 1 (OCT1) and UDP-glucuronosyltransferase 2B7 (UGT2B7) on age
      dependent morphine clearance were evaluated in a cohort of critically ill
      neonatal patients using an opportunistic sampling design. Our primary results
      demonstrate the significant influence of OCT1 genotype (P < 0.05) and gestational
      age (P <= 0.005) on morphine PKs. A physiologically based pharmacokinetic (PBPK)
      model for morphine that accounted for OCT1 ontogeny and PG effect in post-term
      neonates adequately described the clinically observed variability in morphine
      PKs. This study serves as a proof of concept for genotype-dependent drug
      transporter ontogeny in neonates.

PMID- 30300923
TI  - Pressure-Induced Stable Binary Compounds of Magnesium and Germanium.
AB  - Motivated by the possibility to obtain unusual stoichiometric compounds (e.g., Na
      Cl and Mg-O systems) with exotic properties at high pressures, we systematically
      investigated the high-pressure structures and chemical bonding of Mg-Ge systems
      by using a structure-searching method and first-principles calculations. Compared
      with the stable composition of Mg2 Ge at ambient pressure, several
      stoichiometries (e.g., Mg3 Ge, MgGe, and MgGe2 ) were predicted to be stable
      under high pressures. The Pm 3? m Mg3 Ge structure consists of a 12-fold
      coordinated face-sharing GeMg12 cuboctahedron, whereas the P4/mmm MgGe and Cmcm
      MgGe2 phases form MgGe8 hexahedrons and MgGe4 polygons, respectively. All the
      stable phases of Mg-Ge compounds under high pressures exhibit metallic features
      owing to overlap between the conduction and valence bands. For Cmcm MgGe2 , the
      projected density of states near the Fermi energy mainly derive from Ge s, Ge p,
      and Ge d, which are responsible for its metallicity. The calculated
      superconducting critical temperature values of Cmcm Mg2 Ge and P4/mmm MgGe reach
      10.3 and 9.07 K at 5 GPa, respectively.

PMID- 30300924
TI  - Addition of the C-terminus of CD6 to a chimeric antigen receptor enhances
      cytotoxicity and does not compromise expression.
AB  - T cells expressing chimeric antigen receptors (CARs) are a promising new cancer
      immunotherapy that has now reached the clinic. CARs are synthetic receptors that
      redirect T cells towards a tumour-associated antigen and activate them through
      various fused signalling regions, for example derived from CD3zeta, 4-1BB or
      CD28. Analysis of the optimal combination of CAR components including signalling
      domains is not yet comprehensive and may vary with the particular application.
      The C-terminus of the T-cell surface receptor CD6 is critical for its co
      stimulatory effects and signals through two phospho-tyrosine motifs that bind to
      the intracellular adaptor proteins GADS and SLP-76. Addition of the C terminus of
      CD6 did not compromise CAR expression, showing it was a stable moiety that can be
      used independently of the native receptor. A third-generation CAR containing 4
      1BB, CD3zeta and the C terminus of CD6 (4-1BBz-CD6) enhanced interferon-gamma
      release and cytotoxicity when compared with the second-generation 4-1BB CD3zeta
      (4-1BBz) CAR. The CD6 C terminus is a valuable addition to potential components
      for modular design of CARs to improve effector function, particularly
      cytotoxicity.

PMID- 30300925
TI  - Connexin and pannexin (hemi)channels: emerging targets in the treatment of liver
      disease.
AB  - Connexin proteins are the building blocks of hemichannels, which dock further
      between adjacent cells to form gap junctions. Gap junctions control the
      intercellular exchange of critical homeostasis regulators. By doing so, gap
      junctions control virtually all aspects of the hepatic life cycle. In the last
      decade, it has become clear that connexin hemichannels also provide a pathway for
      cellular communication on their own independent of their role as structural
      precursors of gap junctions, namely between the cytosol of an individual cell and
      its extracellular environment. In contrast to gap junctions, connexin
      hemichannels become particularly active in liver disease by facilitating
      inflammation and cell death. This equally holds true for cellular channels
      composed of pannexins, being connexin-like proteins recently identified in the
      liver that gather in structures reminiscent of hemichannels. This paper gives an
      overview of the involvement of connexin-based and pannexin-based channels in non
      cancerous liver disease. This article is protected by copyright. All rights
      reserved.

PMID- 30300926
TI  - Parents' Perceptions and Use of School-Based Body Mass Index Report Cards.
AB  - BACKGROUND: Obesity in children and adolescents has become one of the most
      critical public health problems in the United States. Schools may play an
      important role in raising awareness and possibly slowing the obesity epidemic.
      METHODS: The purpose of this study was to gather information on parents'
      perception and use of body mass index (BMI) report cards provided by public
      schools through the administration of a questionnaire. The questionnaire was
      developed with the assistance of physical educators, pediatricians, and exercise
      scientists. The questionnaires were backpacked home with 1127 students in 6
      Arkansas public schools. Parents completed and returned 404 questionnaires.
      RESULTS: Findings indicate that parents are supportive of schools reporting BMI
      and providing information on healthier lifestyles. However, most parents reported
      not making any adjustment to their child's diet and physical activity habits
      based on the BMI reports. Approximately half of parents (55%) thought the BMI
      report accurately reflected their child's health status. Approximately half of
      the parents reported their child's BMI report led them to think about their
      family's health habits. CONCLUSIONS: Although parents do support receiving BMI
      information from schools, many did not indicate using the data to initiate
      changes such as increased physical activity or healthy eating.

PMID- 30300927
TI  - Correlates of Patient-Centered Medical Home Recognition in School-Based Health
      Centers.
AB  - BACKGROUND: The patient-centered medical home (PCMH) is promoted as a way to
      improve access to care, health care outcomes, and control costs. The
      organizational, environmental, and patient characteristics associated with school
      based health centers (SBHCs) obtaining PCMH recognition is currently unknown. A
      multitheoretical approach was used to explore the correlates of formal PCMH
      recognition in SBHCs. METHODS: The 2013-2014 National Census of School-Based
      Health Centers was used as the primary data source for this analysis.
      Multivariable logistic regression was used to assess the odds of an SBHC
      obtaining any type of PCMH recognition, and obtaining national PCMH recognition.
      RESULTS: Only 29% of SBHCs had received any type of recognition as a PCMH and 17%
      reported receiving national-level recognition. School-based health centers that
      were managed care preferred providers, received Health Resources and Services
      Administration SBHC Capital Funding, and based in schools without adolescents had
      greater odds of both types of PCMH recognition outcomes. High levels of revenue
      from patient billing and more staff were also associated with national PCMH
      recognition. CONCLUSIONS: Financial and personnel resources are needed for
      national-level PCMH recognition, and managed care is supportive of PCMH
      implementation. Efforts should be made to increase medical home activity in SBHCs
      that serve adolescents.

PMID- 30300928
TI  - Well-Being and Academic Achievement: Differences Between Schools From 2002 to
      2010 in the Helsinki Metropolitan Area.
AB  - BACKGROUND: We studied school-level differences in academic achievement and well
      being from 2002 to 2010 in the Helsinki Metropolitan Area, as well as the
      connection between academic achievement, well-being, and socioeconomic
      composition. METHODS: The School Health Promotion Study covered 109 schools and
      78% of schoolchildren (N = 100,413; aged 14 to 16 years). Depression was measured
      with the modified Beck Depression Scale and academic achievement with the grade
      point average. Trajectory analysis identified groups of schools that were as
      heterogeneous over time as possible. RESULTS: Six school trajectories differing
      in academic achievement and 3 in well-being were observed. Differences between
      the trajectories persisted over time. Academic achievement and well-being were
      related: schools on a poor achievement trajectory were more often on a low-well
      being trajectory. The poor socioeconomic composition of students was more common
      in low-academic achievement and well-being trajectories. CONCLUSIONS: Academic
      achievement and well-being differed between schools and are closely related to
      each other and to the school's socioeconomic composition. Differences between the
      schools did not increase over time. Educational policies aimed at reducing
      differences should address both academic achievement and well-being.

PMID- 30300929
TI  - Disparities in Health Risk Behaviors and Health Conditions Among Rhode Island
      Sexual Minority and Unsure High School Students.
AB  - BACKGROUND: Sexual minority students have higher risk for health-related
      behaviors. We examined 5 domains including 34 health risk behaviors and health
      conditions among sexual minorities and unsure students in Rhode Island. We also
      included sexual contact of heterosexually identified students to capture
      heterosexually identified students who may be considered sexual minorities by
      their behavior. METHODS: We used the 2007-2015 Rhode Island Youth Risk Behavior
      Survey data (N = 14,264). We categorized students into 4 groups: students self
      identified as heterosexual and reported no sexual contact with same sex only or
      both sexes (group 1); self-identified as heterosexual and reported sexual contact
      with same sex only or both sexes (group 2); self-identified as lesbian, gay,
      bisexual (group 3); and responded as unsure (group 4). We used multivariable
      adjusted logistic regression analyses to evaluate associations of sexual minority
      and unsure students with 34 health risk behaviors and health conditions
      accounting for complex sampling design. RESULTS: Students in groups 2-4 were more
      likely to engage in health-risk behaviors including violent behaviors, attempted
      suicide, substance use, and no physical activity than their peers. CONCLUSIONS:
      As sexual minority youth continue to report higher rates of health-related risk
      behaviors, targeted evidence-based prevention approaches must focus on reducing
      these risk behaviors among those youth.

PMID- 30300930
TI  - No Association Between Active Commuting to School, Adiposity, Fitness, and
      Cognition in Spanish Children: The MOVI-KIDS Study.
AB  - BACKGROUND: Walking and bicycling (active commuting) to school may be a useful
      strategy to increase the daily amount of physical activity, and, potentially,
      improve children's health. However, it is unclear whether active commuting to
      school (ACS) has the potential to improve physical health and cognitive
      performance in children. Our aim was to examine the relationship between ACS with
      adiposity indicators, physical fitness, and cognitive performance in 4- to 7-year
      old children. METHODS: We conducted a cross-sectional study with 1159 children
      from the provinces of Cuenca and Ciudad Real, Spain. ACS was self-reported by
      parents. Adiposity (body mass index, waist circumference, body fat mass, and
      triceps skinfold thickness) and physical fitness (cardiorespiratory and muscular
      fitness) were measured by standard procedures. Cognitive performance was assessed
      using the Battery of General and Differential Aptitudes. Data analysis included
      analysis of covariance. RESULTS: We found no differences in adiposity, physical
      fitness, and cognitive performance between active commuters and nonactive
      commuters. CONCLUSIONS: Walking to school had no positive impact on adiposity,
      physical fitness, and cognition in 4- to 7-year-old children. Future studies
      should examine the intensity and duration of walking to school needed to provide
      benefits in health and cognitive performance.

PMID- 30300931
TI  - Schoolteachers' and Administrators' Perceptions of Concussion Management and
      Implementation of Return-to-Learn Guideline.
AB  - BACKGROUND: Concussions are a public health concern and concussion management in
      school requires a team approach. We examined schoolteachers' and administrators'
      perceptions of concussions, management, and implementation of return-to-learn
      (RTL) guidelines. METHODS: We audio-recorded and transcribed semistructured
      interviews with teachers (N = 16) and administrators (N = 6) from a public school
      system. We analyzed data using an analytic induction and constant comparison
      approach. RESULTS: Two themes emerged: different understanding, and school
      context. Participants with no sport coaching experience were less familiar with
      concussions than those who coached a sport. Participants with personal experience
      with concussions were more sympathetic toward concussed students' needs. Teachers
      expressed feeling ill-equipped to implement RTL guidelines without specific
      instructions in the complex school environment. However, school administrators
      had minimal understanding of teacher-described challenges. CONCLUSIONS: Teachers
      and administrators recognize that concussions are a health concern, but differ in
      their perceptions of concussions, management, and implementation of RTL
      guidelines. Personal experiences mediate individual perceptions about
      concussions. The daily realities of a school environment complicate teachers'
      capacity to implement RTL guidelines. Conversely, school administrators did not
      express awareness of any challenges with concussion management. To best
      facilitate students' recovery schools should include all stakeholders when
      devising concussion management policies.

PMID- 30300932
TI  - Systematic Review: Frameworks Used in School-Based Interventions, the Impact on
      Hispanic Children's Obesity-Related Outcomes.
AB  - BACKGROUND: Childhood obesity among Hispanic children is a public health concern
      in the United States and Mexico. Although experiences from school-based
      intervention programs aimed at influencing obesity-related behaviors have been
      positive, the understanding of those framework elements that are associated with
      successful outcomes is limited. The purpose of this study was to examine the
      frameworks used within school-based intervention programs in the United States
      and Mexico that showed improvements in obesity-related outcomes among Hispanic
      children. METHODS: A systematic review of the literature was conducted using 4
      electronic databases. Inclusion criteria included: incorporating a framework or
      aspects of frameworks within an intervention, more than 50% of Hispanic children
      used in the study and obesity-related outcomes (eg, dietary behaviors and
      anthropometric measurements). Data extraction and evaluation were completed using
      the Academy of Nutrition and Dietetics Evidence Analysis Manual. RESULTS: Ten
      articles (United States = 4; Mexico = 6) meeting inclusion criteria were
      evaluated. Eight studies that included a community-based framework, intensive
      nutrition education, and continuous communication among stakeholders resulted in
      improvements in dietary behaviors and anthropometric measurements among children
      compared to control groups. CONCLUSIONS: Incorporating community-based frameworks
      may increase the efficacy of school-based intervention programs to reduce obesity
      related outcomes among Hispanic children.

PMID- 30300933
TI  - Bullying Victimization in Schools: Why the Whole School, Whole Community, Whole
      Child Model Is Essential.
AB  - BACKGROUND: Bullying is more likely to happen in schools than in any other
      location. The purpose of this study is to use decision tree analyses to predict
      specific risk factors for bullying to identify areas of interest for school-based
      bullying prevention. METHODS: We obtained data from the 2013 National Crime
      Victimization Study (NCVS) School Crime Supplement. We used case-wise deletion to
      create a sample with completed data based on the measure of bullying (N = 4967).
      The dependent variable for this study was bullying. We used chi-square automatic
      interaction detection (CHAID) to uncover predictors of bullying victimization in
      schools. RESULTS: Results suggest that 21.7% of the participants were bullied
      during the 6 months prior to the survey. Being distracted in class and being
      involved in a fight were the top statistically significant variables for bullying
      victimization in schools. Fear of being attacked and seeing hate-related words or
      symbols in school were also strong predictors of bullying. CONCLUSIONS: Bullying
      victimization can often be predicted. Therefore, school personnel can implement
      programs and policies consistent with the Whole School, Whole Community, Whole
      Child (WSCC) model to improve the social and emotional climate in schools and
      proactively reduce opportunities for bullying victimization.

PMID- 30300934
TI  - Evaluation of the Process of Implementing an Outdoor School Ground Smoking Ban at
      Secondary Schools.
AB  - BACKGROUND: Although outdoor smoking bans at school are becoming important, it
      remains unclear whether successful implementation is feasible and what conditions
      promote it. Therefore, this study evaluates the implementation process by
      identifying important factors. METHODS: Interviews were held with directors of 24
      secondary schools that had decided to implement an outdoor school ground smoking
      ban, to identify important factors during implementation. Additionally,
      observations were made before and (about 4 weeks) after implementation to
      evaluate adherence to guidelines. Data were analyzed using a thematic approach.
      RESULTS: During implementation, the following items were important: smoking ban
      (eg, guidelines), school (eg, policy, enforcement, environmental factors,
      resources, etc), and external factors (eg, social environment). Four schools were
      unable to implement the ban, 20 schools implemented the ban but student adherence
      was low, and at 4 schools, staff members still smoked on school grounds.
      CONCLUSIONS: Although implementation is feasible, there are challenges. Schools
      need to apply a phased/dynamic process with ample lead time and clear
      communication of the policy. Directors should deal with offenders by strictly
      enforcing the ban and helping them stop smoking. This study offers information to
      help institutes implement an outdoor smoking ban to further protect adolescents
      from the harm of smoking.

PMID- 30300935
TI  - Community phylogeny of the globally critically imperiled pine rockland ecosystem.
AB  - PREMISE OF THE STUDY: Community phylogenetic methods incorporate information on
      evolutionary relationships into studies of organismal assemblages. We used a
      community phylogenetic framework to investigate relationships and biogeographic
      affinities and to calculate phylogenetic signal of endemism and invasiveness for
      the flora of the pine rocklands-a globally critically imperiled ecosystem with a
      significant portion of its distribution in South Florida, United States. METHODS:
      We reconstructed phylogenetic relationships of 538 vascular plant taxa, which
      represent 92.28% of the vascular flora of the pine rocklands. We estimated
      phylogenetic signal for endemism and invasiveness using phylogenetic generalized
      linear mixed models. We determined the native range for each species in the data
      set and calculated the total number of species sourced from each region and all
      possible combinations of these regions. KEY RESULTS: The pine rockland flora
      includes representatives of all major vascular plant lineages, and most species
      have native ranges in the New World. There was strong phylogenetic signal for
      endemism, but not for invasiveness. CONCLUSIONS: Community phylogenetics has high
      potential value for conservation planning, particularly for fragmented and
      endangered ecosystems like the pine rockland. Strong phylogenetic signal for
      endemic species in our data set, which also tend to be threatened or endangered,
      can help to identify species at risk, as well as fragments where those species
      occur, highlighting conservation priorities. Our results indicate, at least in
      the pine rockland ecosystem, no phylogenetic signal for invasive species, and
      thus other information must be used to predict the potential for invasiveness.

PMID- 30300936
TI  - Interprofessional Intervention to Improve Geriatric Consultation Timing on an
      Acute Medical Service.
AB  - OBJECTIVES: To determine whether an interprofessional intervention would improve
      the use and timing of a geriatric consultation on a hospitalist service. DESIGN:
      Difference-in-differences (DID), which measures the difference in improvement
      over time between intervention and control team patients attributable to the
      intervention. SETTING: 1,000-bed U.S. academic medical center. PARTICIPANTS:
      Individuals aged 60 and older admitted to a general medicine hospitalist service
      (N=7,038; n = 718 on intervention teams, n = 686 historical controls, n = 5,634
      on control teams (concurrent and historic). INTERVENTION: On 2 of 11 hospitalist
      teams, a geriatrician attended multidisciplinary discharge rounds twice weekly
      and advised on the benefits of a geriatric consultation for individuals aged 60
      and older. MEASUREMENTS: Primary outcome was percentage of hospitalizations
      resulting in a geriatric consultation. Secondary outcome was days to geriatric
      consultation. Both outcomes were controlled for age, sex, comorbidity, mean daily
      intensity of inpatient care utilization, and admission in the prior 30 days. In
      the primary analysis, length of stay was controlled. RESULTS: Intervention
      participants were more likely to have a geriatric consultation (DID = 2.35%
      absolute percentage points, 95% confidence interval (CI) = 0.59-4.39%) and to
      have a consultation sooner (DID = 3.61 fewer days, 95% CI = -1 to -7).
      CONCLUSION: An interprofessional intervention that focused on hospitalist
      ordering practices increased use of appropriate geriatric consultation and
      decreased time to consultation. This model of interprofessional effort is
      effective. Future adaptations are needed to target scarce geriatric resources
      without increasing overall use.

PMID- 30300937
TI  - Ticket to spawn: Combining economic and genetic data to evaluate the effect of
      climate and demographic structure on spawning distribution in Atlantic cod.
AB  - Climate warming and harvesting affect the dynamics of species across the globe
      through a multitude of mechanisms, including distribution changes. In fish,
      migrations to and distribution on spawning grounds are likely influenced by both
      climate warming and harvesting. The Northeast Arctic (NEA) cod (Gadus morhua)
      performs seasonal migrations from its feeding grounds in the Barents Sea to
      spawning grounds along the Norwegian coast. The distribution of cod between the
      spawning grounds has historically changed at decadal scales, mainly due to
      variable use of the northern and southern margins of the spawning area. Based on
      historical landing records, two major hypotheses have been put forward to explain
      these changes: climate and harvesting. Climate could affect the distribution
      through, for example, spatial habitat shifts. Harvesting could affect the
      distribution through impacting the demographic structure. If demographic
      structure is important, theory predicts increasing spawner size with migration
      distance. Here, we evaluate these hypotheses with modern data from a period (2000
      2016) of increasing temperature and recovering stock structure. We first analyze
      economic data from the Norwegian fisheries to investigate geographical
      differences in size of spawning fish among spawning grounds, as well as
      interannual differences in mean latitude of spawning in relation to changes in
      temperature and demographic parameters. Second, we analyze genetically determined
      fish sampled at the spawning grounds to unambiguously separate between migratory
      NEA cod and potentially smaller sized coastal cod of local origin. Our results
      indicate smaller spawners farther away from the feeding grounds, hence not
      supporting the hypothesis that harvesting is a main driver for the contemporary
      spawning ground distribution. We find a positive correlation between annual mean
      spawning latitude and temperature. In conclusion, based on contemporary data,
      there is more support for climate compared to harvesting in shaping spawning
      ground distribution in this major fish stock in the North Atlantic Ocean.

PMID- 30300938
TI  - Weighing of Evidence by Health Technology Assessment Bodies: Retrospective Study
      of Reimbursement Recommendations for Conditionally Approved Drugs.
AB  - This study assessed whether five Health Technology Assessment (HTA) bodies in
      Europe were more negative about drugs with a Conditional Marketing Authorization
      (CMA) that are approved without controlled studies compared to CMA drugs that are
      approved based on controlled studies. The HTA recommendations were categorized
      into positive, restricted, and negative. A total of 92 HTA recommendations were
      available for 27 drugs. Thirty of 62 (48%) and 17 of 30 (57%) of the
      recommendations were negative for drugs with and without controlled studies,
      respectively. Overall, only 12 (13%) recommendations were positive. In all
      jurisdictions, recommendations between drugs with and drugs without controlled
      data were comparable, which suggests that the presence of controlled data is not
      decisive in HTA evaluations. The small proportion of unrestricted positive
      recommendations highlights difficulties with recommending the drugs in this
      cohort, which may be caused by scientific uncertainty or other factors. Earlier
      collaboration between stakeholders is advised in order to improve patient access.

PMID- 30300939
TI  - In Situ/Operando X-ray Spectroscopies for Advanced Investigation of Energy
      Materials.
AB  - Issues related to energy and the environment have now become of central and
      crucial importance in our societies. Low-carbon green energy will have a critical
      role in a necessary third industrial revolution. To reduce global greenhouse gas
      emissions in response to globalization and increasingly stringent carbon emission
      policies, large scale green energy production technologies must be established
      worldwide. A new age of human demand for green energy is thus coming and
      scientists are focused on finding new functional efficient and low-cost materials
      to generate clean and sustainable energy. Improving the energy conversion,
      generation, and storage efficiency of energy materials has always been a daunting
      challenge. For many important energy material systems, such as nanostructured
      catalysts, artificial photosynthetic systems, smart energy saving materials, and
      energy storage devices, monitoring the atomic and electronic structures close to
      the interfacial region in a real working environment is of paramount importance.
      Designing a better-performing material without comprehending its fundamental
      properties such as chemical states, atomic and electronic structures and how they
      are altered close to the interfacial regions during the physical and chemical
      reactions involved in their applications is very challenging. Understanding,
      controlling and tuning the interfaces in energy conversion and storage materials
      requires in situ/operando characterization tools, of which synchrotron X-ray
      spectroscopies, which have several unique features, are very suitable ones. X-ray
      absorption spectroscopy can be used to elucidate the local unoccupied electronic
      structure in the conduction band, and X-ray emission spectroscopy can be used to
      characterize the occupied electronic structure in the valence band. The derived
      resonant inelastic X-ray scattering reveals inter- and/or intra-electric
      transitions (i.e. d-d, f-f excitation and charge-transfer excitation) that
      reflect intrinsic chemical and physical properties. Scanning transmission X-ray
      microscopy is a chemical mapping technique with elemental sensitivity and spatial
      selectivity, which can therefore yield information about chemical composition in
      various spatial regions. This unique characteristic makes the method effective
      for investigating interfacial phenomena (such as electron transport, interface
      formation/deformation, defects, doping etc.). In situ/operando approaches have
      made the probing and understanding of changes in the atomic and electronic
      structures of energy materials in an operational environment feasible. This
      article presents a perspective of the pioneering developments as well as the
      recent achievements in in situ/operando synchrotron X-ray spectroscopies for the
      advanced investigation of energy materials. Four major energy material systems
      are identified: energy storage, energy generation, energy conversion, and energy
      saving material systems. Selected representative investigations of each systems
      are showcased and discussed demonstrating that in situ/operando synchrotron X-ray
      spectroscopy is truly essential for unraveling better fundamental knowledge for
      mechanism understanding and efficiency optimization of existing and emerging
      energy material systems.

PMID- 30300940
TI  - 5-Oxyacetic Acid Modification Destabilizes Double Helical Stem Structures and
      Favors Anionic Watson-Crick like cmo5 U-G Base Pairs.
AB  - Watson-Crick like G-U mismatches with tautomeric Genol or Uenol bases can evade
      fidelity checkpoints and thereby contribute to translational errors. The 5
      oxyacetic acid uridine (cmo5 U) modification is a base modification at the wobble
      position on tRNAs and is presumed to expand the decoding capability of tRNA at
      this position by forming Watson-Crick like cmo5 Uenol -G mismatches. A detailed
      investigation on the influence of the cmo5 U modification on structural and
      dynamic features of RNA was carried out by using solution NMR spectroscopy and UV
      melting curve analysis. The introduction of a stable isotope labeled variant of
      the cmo5 U modifier allowed the application of relaxation dispersion NMR to probe
      the potentially formed Watson-Crick like cmo5 Uenol -G base pair. Surprisingly,
      we find that at neutral pH, the modification promotes transient formation of
      anionic Watson-Crick like cmo5 U- -G, and not enolic base pairs. Our results
      suggest that recoding is mediated by an anionic Watson-Crick like species, as
      well as bring an interesting aspect of naturally occurring RNA modifications into
      focus-the fine tuning of nucleobase properties leading to modulation of the RNA
      structural landscape by adoption of alternative base pairing patterns.

PMID- 30300941
TI  - "We Take Care of Patients, but We Don't Advocate for Them": Advance Care Planning
      in Prison or Jail.
AB  - OBJECTIVES: To investigate correctional healthcare providers' knowledge of and
      experience with advance care planning (ACP), their perspectives on barriers to
      ACP in correctional settings, and how to overcome those barriers. DESIGN:
      Qualitative. SETTING: Four prisons in 2 states and 1 large city jail in a third
      state. PARTICIPANTS: Correctional healthcare providers (e.g., physicians, nurses,
      social workers; N=24). RESULTS: Participants demonstrated low baseline ACP
      knowledge; 85% reported familiarity with ACP, but only 42% provided accurate
      definitions. Fundamental misconceptions included the belief that providers
      provided ACP without soliciting inmate input. Multiple ACP barriers were
      identified, many of which are unique to prison and jail facilities, including
      provider uncertainty about the legal validity of ACP documents in prison or jail,
      inmate mistrust of the correctional healthcare system, inmates' isolation from
      family and friends, and institutional policies that restrict use of ACP.
      Clinicians' suggestions for overcoming those barriers included ACP training for
      clinicians, creating psychosocial support opportunities for inmates, revising
      policies that limit ACP, and systematically integrating ACP into healthcare
      practice. CONCLUSION: Despite an increasing number of older and seriously ill
      individuals in prisons and jails, many correctional healthcare providers lack
      knowledge about ACP. In addition to ACP barriers found in the community, there
      are unique barriers to ACP in prisons and jails. Future research and policy
      innovation are needed to develop clinical training programs and identify ACP
      implementation strategies for use in correctional settings.

PMID- 30300942
TI  - Light-Induced Gold-Catalyzed Hiyama Arylation: A Coupling Access to
      Biarylboronates.
AB  - Organoboron compounds are versatile synthetic building blocks. We herein report a
      new strategy, a photochemical gold-catalyzed chemo-selective Hiyama arylation of
      B,Si bifunctionalized reagents with diazonium salts, which is orthogonal to
      common strategies and therefore a unique tool for synthesis of valuable
      biarylboronates. With this new methodology a wide array of diversely
      functionalized sp2 - and sp3 -hybridized biarylboronates were obtained. Notably,
      the synergism of gold catalysis with copper catalysis or palladium catalysis,
      allows for one-pot iterative C-X (heteroatom) and C-C couplings for the rapid
      assembly of several simple fragments to relatively complex molecules. Mechanistic
      studies indicated that photosensitizer-free conditions were superior to
      gold/Ru(bpy)3 Cl2 dual catalysis.

PMID- 30300943
TI  - FERONIA mutation induces high levels of chloroplast-localized Arabidopsides which
      are involved in root growth.
AB  - The FERONIA (FER) signaling pathway is known to have diverse roles in Arabidopsis
      thaliana, such as growth, reproduction, and defense, but how this receptor kinase
      is involved in various biological processes is not well established. In this
      work, we applied multiple mass spectrometry techniques to identify metabolites
      involved in the FER signaling pathway and to understand their biological roles. A
      direct infusion Fourier transform ion cyclotron resonance (FT-ICR)-MS approach
      was used for initial screening of wild-type and feronia (fer) mutant plant
      extracts, and Arabidopsides were found to be significantly enriched in the
      mutant. As Arabidopsides are known to be induced by wounding, further experiments
      on wounded and non-wounded leaf samples were carried out to investigate these
      oxylipins as well as related phytohormones using a quadrupole-time-of-flight (Q
      TOF) MS by direct injection and LC-MS/MS. In a root growth bioassay with
      Arabidopside A isolated from fer mutants, the wild-type showed significant root
      growth inhibition compared with the fer mutant. Our results therefore implicated
      Arabidopsides, and Arabidopside A specifically, in FER functions and/or
      signaling. Finally, matrix-assisted laser desorption/ionization MS imaging (MALDI
      MSI) was used to visualize the localization of Arabidopsides, and we confirmed
      that Arabidopsides are highly abundant at wounding sites in both wild-type and
      fer mutant leaves. More significantly, five micron high-spatial resolution MALDI
      MSI revealed that Arabidopsides are localized to the chloroplasts where many
      stress signaling molecules are made.

PMID- 30300944
TI  - Maternal paracetamol intake and fetal ductus arteriosus constriction or closure:
      a case series analysis.
AB  - Recent case reports describe an association between maternal paracetamol intake
      and fetal ductus arteriosus constriction or closure. To put these cases into
      perspective and explore causality, a structured literature search was conducted.
      The World Health Organization Uppsala Monitoring Centre (WHO-UMC) causality tool
      was applied to the cases retrieved. The search resulted in 12 papers with 25 case
      descriptions, of which one case was classified as unlikely, nine as possible, 11
      as probable and four as certain. Consequently, we concluded that a causal
      relationship between maternal paracetamol intake and fetal ductus arteriosus
      constriction or closure is likely. These findings suggest that pharmacovigilance
      studies on paracetamol safety during pregnancy are warranted to quantify the
      event and put the current findings into clinical perspective. Although analgesia
      during pregnancy and during the peripartum period is of obvious relevance,
      alternative analgesics such as opioids or other nonsteroidal anti-inflammatory
      drugs also have side effects.

PMID- 30300946
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 42/2018.

PMID- 30300945
TI  - Quantitative phosphoproteomic analysis reveals common regulatory mechanisms
      between effector- and PAMP-triggered immunity in plants.
AB  - Plant immunity consists of two arms: pathogen-associated molecular pattern (PAMP)
      triggered immunity (PTI), induced by surface-localized receptors, and effector
      triggered immunity (ETI), induced by intracellular receptors. Despite the little
      structural similarity, both receptor types activate similar responses with
      different dynamics. To better understand phosphorylation events during ETI, we
      employed a phosphoproteomic screen using an inducible expression system of the
      bacterial effector avrRpt2 in Arabidopsis thaliana, and identified 109
      differentially phosphorylated residues of membrane-associated proteins on
      activation of the intracellular RPS2 receptor. Interestingly, several RPS2
      regulated phosphosites overlap with sites that are regulated during PTI,
      suggesting that these phosphosites may be convergent points of both signaling
      arms. Moreover, some of these sites are residues of important defense components,
      including the NADPH oxidase RBOHD, ABC-transporter PEN3, calcium-ATPase ACA8,
      noncanonical Galpha protein XLG2 and H+ -ATPases. In particular, we found that
      S343 and S347 of RBOHD are common phosphorylation targets during PTI and ETI. Our
      mutational analyses showed that these sites are required for the production of
      reactive oxygen species during both PTI and ETI, and immunity against avirulent
      bacteria and a virulent necrotrophic fungus. We provide, for the first time,
      large-scale phosphoproteomic data of ETI, thereby suggesting crucial roles of
      common phosphosites in plant immunity.

PMID- 30300947
TI  - Potentially Inappropriate Medications in Older Adults: Deprescribing with a
      Clinical Pharmacist.
AB  - OBJECTIVES: To compare the effects of a Geriatric Patient-Aligned Care Team
      (GeriPACT) on deprescribing of potentially inappropriate medications (PIMs) in
      individuals aged 80 and older with usual care (UC) in the Veterans Affairs
      setting. DESIGN: Retrospective cohort study. SETTING: Veterans Affairs Medical
      Center in Lexington, Kentucky. PARTICIPANTS: Individuals aged 80 and older who
      filled a PIM at least 90 days before a GeriPACT or primary care appointment
      between January 1, 2015, and September 6, 2017 (N = 568). MEASUREMENTS: The
      primary outcome was to determine whether an interdisciplinary team (IDT)
      including a clinical pharmacy specialist (CPS) resulted in greater deprescribing
      of PIMs for older adults than UC. RESULTS: One hundred twenty-one (26.8%) PIMs
      were deprescribed in GeriPACT, compared with 73 (16.1%) in UC (p = <.001). Of
      PIMs not deprescribed, 9.7% (n = 32) were dose reduced in GeriPACT, versus 2.8%
      (n = 11) in UC (p < .001). Documentation of risk versus benefit discussion
      between a provider and participant or pharmacist and participant occurred with
      65.2% (n = 215) of PIMs not deprescribed in GeriPACT and 0.003% (n = 1) in UC (p
      < .001). CONCLUSION: An IDT that included a CPS led to significantly more
      deprescribing of PIMs in older veterans. Including a CPS on an IDT for the
      management of older adults can decrease PIM use in our rapidly growing aging
      population.

PMID- 30300948
TI  - Report of the Office of Population Affairs' expert work group meeting on short
      birth spacing and adverse pregnancy outcomes: Methodological quality of existing
      studies and future directions for research.
AB  - BACKGROUND: The World Health Organization (WHO) recommends that women wait at
      least 24 months after a livebirth before attempting a subsequent pregnancy to
      reduce the risk of adverse maternal, perinatal, and infant health outcomes.
      However, the applicability of the WHO recommendations for women in the United
      States is unclear, as breast feeding, nutrition, maternal age at first birth, and
      total fertility rate differs substantially between the United States and the low-
      and middle-resource countries upon which most of the evidence is based. METHODS:
      To inform guideline development for birth spacing specific to women in the United
      States, the Office of Population Affairs (OPA) convened an expert work group
      meeting in Washington, DC, on 14-15 September 2017 among reproductive, perinatal,
      paediatric, social, and public health epidemiologists; obstetrician
      gynaecologists; biostatisticians; and experts in evidence synthesis related to
      women's health. RESULTS: Presentations and discussion topics included the
      methodological quality of existing studies, evaluation of the evidence for causal
      effects of short interpregnancy intervals on adverse perinatal and maternal
      health outcomes, good practices for future research, and identification of
      research gaps and priorities for future work. CONCLUSIONS: This report provides
      an overview of the presentations, discussions, and conclusions from the expert
      work group meeting.

PMID- 30300949
TI  - Workplace violence perpetrated by clients of health care: A need for safety and
      trauma-informed care.
AB  - AIMS: To examine the relationship between workplace violence perpetrated by
      clients, their innate neurophysiological response to dis-ease and the resulting
      interactions with healthcare providers. BACKGROUND: Client-on-worker violence
      remains a problem globally. Workplace violence risk factors have been documented.
      A gap remains in understanding what has happened to clients that perpetrate
      violence, and the link between adverse childhood experiences (ACE), the
      neuroscience of threat and trauma-informed care. DESIGN: This explanatory study
      was part of a larger descriptive study. METHODS: Managers, directors,
      health/safety staff, nurses and educators (n = 99) from Australian rural and
      metropolitan health services participated in individual and group interviews.
      Following inductive thematic analysis, a secondary analysis, informed by
      understandings of ACE, polyvagal theory and trauma-informed care, was conducted.
      Analysis was guided by the question: What happens to clients that causes them to
      instigate violence against healthcare workers? Reporting of this research adheres
      to the COREQ guidelines. RESULTS: Clients can react aggressively when under
      perceived threat. Themes included are as follows: client stress and trauma,
      previous client trauma, impact of care provision on client and trauma-informed
      care. CONCLUSION: Healthcare services can be experienced as stressful
      environments. Coupled with high incidences of past trauma, clients' assessment of
      risk and safety can be compromised resulting in inappropriate reactivity when
      staff are trying to provide care. Care provision can be perceived as a threat to
      clients' physical and psychological safety, activating the fight protective
      response resulting in aggression. Understanding and applying neuroscience and
      implementing a cultural change of trauma-informed care have the potential to
      reduce workplace violence. Even with these understandings, it is imperative that
      healthcare staff are protected and feel safe at work. RELEVANCE TO CLINICAL
      PRACTICE: Understanding trauma and the neuroscience of threat and safety can
      assist staff to understand what happens to clients that causes them to instigate
      violence against healthcare providers and implement systems and strategies to
      respond to such threat.

PMID- 30300950
TI  - Enantioselective Synthesis of Chiral-at-Sulfur 1,2-Benzothiazines by Cpx RhIII 
      Catalyzed C-H Functionalization of Sulfoximines.
AB  - Sulfoximines with stereogenic sulfur atoms are attractive structural motifs in
      drug discovery. A direct catalytic enantioselective method for the synthesis of
      sulfur-chiral 1,2-benzothiazines from readily accessible diaryl sulfoximines is
      presented. Rhodium(III) complexes equipped with chiral cyclopentadienyl ligands
      and paired with suitable carboxylic acid additives engage in an
      enantiodetermining C-H activation directed by the sulfoximine group. Subsequent
      trapping of the rhodacycle with a broad range of diazoketones gives access to S
      chiral 1,2-benzothiazines with synthetically highly attractive substitution
      patterns in good yields and enantioselectivities.

PMID- 30300951
TI  - Analyte-Substrate Interactions at Functionalized Tip-Electrospray Ionization Mass
      Spectrometry: Molecular Mechanisms and Applications.
AB  - Conventional electrospray ionization mass spectrometry (ESI-MS) commonly uses
      capillary tip for sample introduction and ionization. In recent years, ESI-MS
      using non-capillary substrate tips has attracted growing interest as it allows
      separation and enrichment of analytes from complex samples due to the analytes
      substrate interactions. In this work, model mixtures and functionalized tips were
      employed to investigate the molecular mechanism of the analyte-substrate
      interactions. The mixtures were directly loaded on substrate tips, and then
      temporal responses of analytes were investigated by monitoring selected ion
      chromatogram (SIC) responses of each analyte. It is found that movements of bulk
      solution on substrate surface was firstly occurred that all analytes are sprayed
      out together, and then sequential ionization of analytes were observed on
      substrate surface which were affected by the analytes-substrate interactions in
      which weaker interaction were easier to be faster moved on substrate tips and the
      stronger interactions caused the target analyte to be retained on the substrate.
      The main molecular mechanisms of analyte-substrate interactions were revealed to
      be hydrophobic interactions and electrostatic interactions. Furthermore, based on
      the mechanistic insights, functionalized tips were further applied for rapid
      extractive sampling of target analytes from complex samples with good analytical
      performances. Overall, this study on the mechanism and applications of analyte
      substrate interactions is useful for understanding of the fundamental principles
      and further developments of functionalized TESI.

PMID- 30300952
TI  - PI3Kdelta Is a Therapeutic Target in Hepatocellular Carcinoma.
AB  - Class I phosphoinositide 3-kinase (PI3K) signaling is a major pathway in human
      cancer development and progression. Among the four PI3K isoforms, PI3Kalpha and
      PI3Kbeta are ubiquitously expressed, whereas PI3Kgamma and PI3Kdelta are found
      primarily in leukocytes. Until now, PI3K targeting in solid tumors has focused on
      inhibiting PI3Kalpha-mediated and PI3Kbeta-mediated cancer cell-intrinsic PI3K
      activity. The role of PI3Kdelta in solid tumors is unknown. Here, we evaluated
      the effects of PI3Kdelta using established hepatocellular carcinoma (HCC) cells,
      malignant hepatocytes derived from patients with advanced HCC, murine models, and
      HCC tissues using RNA sequencing, quantitative PCR, immunoblotting,
      immunofluorescence, microarray, liquid chromatography-tandem mass spectrometry,
      and kinase assay. We established a chemical carcinogenesis model of liver
      malignancy that reflects the malignant phenotype and the in vivo environment of
      advanced HCC. In this in vivo advanced HCC-mimic system using HCC cells treated
      with hydrogen peroxide (H2 O2 ), we showed that H2 O2 selectively increases
      PI3Kdelta activity while decreasing that of other class I PI3Ks. Blocking
      PI3Kdelta activity with a PI3Kdelta inhibitor or small interfering RNA-mediated
      PI3Kdelta gene silencing inhibited HCC-cell proliferation and dampened key
      features of malignant HCC, including the up-regulation of telomerase reverse
      transcriptase (TERT). Mechanistically, H2 O2 induced oxidative modification of
      the serpin peptidase inhibitor, serpin peptidase inhibitor (SERPINA3), blocking
      its ubiquitin-dependent degradation and enhancing its activity as a
      transcriptional activator of PI3Kdelta and TERT. High PI3Kdelta levels in HCC
      were found to correlate with poor survival rates, with human advanced HCC showing
      positive correlations between the protein levels of oxidized SERPINA3, PI3Kdelta,
      and TERT. Thus, PI3Kdelta plays significant roles in malignant liver tumors.
      Conclusion: Our data identify PI3Kdelta inhibition, recently approved for the
      treatment of human B-cell malignancies, as a potential treatment for HCC.

PMID- 30300953
TI  - Reply to: Hands-free but Nonwearable Technology Needed for Outpatient Clinical
      Gait-speed Assessment.

PMID- 30300954
TI  - PHOTOIONIZATION AND PHOTOFRAGMENTATION IN MASS SPECTROMETRY WITH VISIBLE AND UV
      LASERS.
AB  - Ever since the introduction of laser technology to the field of mass
      spectrometry, several disciplines evolved providing solutions to challenging
      scientific and analytical tasks in research and industry. Among these are
      techniques involving multiphoton ionization such as Resonance-Enhanced
      Multiphoton Ionization (REMPI, R2PI) and Mass-Analyzed Threshold Ionization
      (MATI) spectroscopy, a variant of Zero Kinetic Energy (ZEKE) spectroscopy, that
      possess the ability to selectively ionize certain preselected compounds out of
      complex mixtures, for example, environmental matrices, with a high level of
      efficiency. Another key feature of multiphoton ionization techniques is the
      ability to control the degree of fragmentation, whereas soft ionization is most
      highly appreciated in most applications. In cases where rich fragmentation
      patterns are desired for diagnostic purposes, Photodissociation mass spectrometry
      (PD-MS) is applied successfully. PD-MS allows for the cleavage of selected
      chemical bonds. With the introduction of chromophoric labels in PD-MS, it became
      possible to target certain molecules or groups within a molecule. In this review
      article, an overview of the basic principles and experimental requirements of
      REMPI and MATI spectroscopy and PD mass spectrometry are given. By means of
      selected examples, the latest developments and application possibilities in this
      field over the past decade with special focus on the German research landscape
      are pointed out. (c) 2018 Wiley Periodicals, Inc. Mass Spec Rev 9999: XX-XX,
      2018.

PMID- 30300955
TI  - Highly Diastereo- and Enantioselective Synthesis of Nitrile-Substituted
      Cyclopropanes by Myoglobin-Mediated Carbene Transfer Catalysis.
AB  - A chemobiocatalytic strategy for the highly stereoselective synthesis of nitrile
      substituted cyclopropanes is reported. The present approach relies on an
      asymmetric olefin cyclopropanation reaction catalyzed by an engineered myoglobin
      in the presence of ex situ generated diazoacetonitrile within a compartmentalized
      reaction system. This method enabled the efficient transformation of a broad
      range of olefin substrates at a preparative scale with up to 99.9 % de and ee and
      up to 5600 turnovers. The enzymatic product could be further elaborated to afford
      a variety of functionalized chiral cyclopropanes. This work expands the range of
      synthetically valuable, abiotic transformations accessible through biocatalysis
      and paves the way to the practical and safe exploitation of diazoacetonitrile in
      biocatalytic carbene transfer reactions.

PMID- 30300956
TI  - One-Pot Synthesis of Aryl- and Alkyl S-Perfluoroalkylated NH-Sulfoximines from
      Sulfides.
AB  - A general efficient one-pot synthesis of S-perfluoroalkylated NH-sulfoximines
      from sulfides has been developed using phenyliodine diacetate (PIDA) and ammonium
      carbamate. Remarkable rate enhancement with trifluoroethanol was observed,
      presumably due to H-bonding effects. These mild and metal-free conditions are
      compatible with -CH2 F, -CFCl2 , -CF2 H, -CF2 Br, -C4 F9 , and -CF3 groups, in
      both the alkyl- and aryl series. Based on a 19 F NMR analysis, a lambda6 
      acetoxysulfanenitrile intermediate was proposed.

PMID- 30300957
TI  - Xanthocidin Derivatives from the Endophytic Streptomyces sp. AcE210 Provide
      Insight into Xanthocidin Biosynthesis.
AB  - Xanthocidin and six new derivatives were isolated from the endophytic
      Streptomyces sp. AcE210. Their planar structures were elucidated by 1D and 2D NMR
      spectroscopy as well as by HRMS. The absolute configuration of one compound was
      determined by using vibrational circular dichroism spectroscopy (VCD). The
      structural similarities of xanthocidin and some of the isolated xanthocidin
      congeners to the methylenomycins A, B, and C suggested that the biosynthesis of
      these compounds might follow a similar route. Feeding studies with isotopically
      labelled [13 C5 ]-l-valine showed that instead of utilizing acetyl-CoA as starter
      unit, which has been proposed for the methylenomycin biosynthesis, Streptomyces
      sp. AcE210 employs an isobutyryl-CoA starter unit, resulting in a branched side
      chain in xanthocidin. Further evidence for a comparable biosynthesis was given by
      the analysis of the genome sequence of Streptomyces sp. AcE210 that revealed a
      cluster of homologues to the mmy genes involved in methylenomycin biosynthesis.

PMID- 30300958
TI  - A reduction in compliance or activation level reduces residual force depression
      in human tibialis anterior.
AB  - AIM: We investigated if residual force depression (rFD) is present during
      voluntary fixed-end contractions of human tibialis anterior (TA) and whether
      reducing TA's activation level after active shortening could reduce rFD. METHODS:
      Ten participants performed fixed-end dorsiflexion contractions to a low, moderate
      or high level while electromyography (EMG), dorsiflexion force and TA ultrasound
      images were recorded. Contractions were force- or EMG-matched and after the low
      or high contraction level was attained, participants respectively increased or
      decreased their force/EMG to a moderate level. Participants also performed
      moderate level contractions while the TA muscle-tendon unit (MTU) was lengthened
      during the force/EMG rise to the reference MTU length. RESULTS: Equivalent
      fascicle shortening over moderate and low to moderate level contractions did not
      alter EMG (P = 0.45) or dorsiflexion force (P = 0.47) at the moderate level.
      Greater initial fascicle shortening magnitudes (1.7 mm; P <= 0.01) to the high
      contraction level did not alter EMG (P = 0.45) or dorsiflexion force (P = 0.30)
      at the subsequent moderate level compared with moderate level contractions. TA
      MTU lengthening during the initial force/EMG rise reduced TA fascicle shortening
      (-2.5 mm; P <= 0.01), which reduced EMG (-3.9% MVC; P < 0.01) and increased
      dorsiflexion force (3.7% MVC; P < 0.01) at the moderate level compared with fixed
      end moderate level contractions. CONCLUSION: rFD is present during fixed-end
      dorsiflexion contractions because fascicles actively shorten as force/EMG
      increases and rFD can be reduced by reducing the effective MTU compliance. A
      reduction in muscle activation level also reduces rFD by potentially triggering
      residual force enhancement-related mechanisms as force drops and some fascicles
      actively lengthen.

PMID- 30300959
TI  - Radical-Mediated Thiol-Ene Strategy: Photoactivation of Thiol-Containing Drugs in
      Cancer Cells.
AB  - Photoactivated drugs provide an opportunity to improve efficacy alongside
      reducing side-effects in the treatment of severe diseases such as cancer.
      Described herein is a photoactivation decaging method of isobutylene-caged thiols
      through a UV-initiated thiol-ene reaction. The method was demonstrated with an
      isobutylene-caged cysteine, cyclic disulfide-peptide, and thiol-containing drug,
      all of which were rapidly and efficiently released under mild UV irradiation in
      the presence of thiol sources and a photoinitiator. Importantly, it is shown that
      the activity of histone deacetylase inhibitor largazole can be switched off when
      stapled, but selectively switched on within cancer cells when irradiated with non
      phototoxic light.

PMID- 30300960
TI  - A Hemicyanine-Embedded Diphenylselenide-Containing Probe "HemiSe" in which SePh2
      Stays Reduced for Selective Detection of Superoxide in Living Cells.
AB  - A simple one-step synthesis of fluorescent probe HemiSe has been developed for
      the detection of superoxide (O2 .- ). The probe undergoes reaction specifically
      with O2 .- when in the presence of other competitive ROS/RNS/metal ions. The
      diphenylselenide was incorporated to completely quench the fluorescence of the
      hemicyanine unit through the action of a photoinduced electron transfer (PET)
      photomechanism. However, after the addition of O2 .- , the latent fluorophore
      regains its fluorescence owing to the reaction at the C=C bond of the hemicyanine
      with O2 .- through nucleophilic attack; the increase in blue emission is due to a
      reaction of the double bond within HemiSe followed by an increase in fluorescence
      quantum yield (Phi) up to 0.45; the limit of detection (LOD) is 11.9 nm. A time
      dependent study shows that HemiSe can detect superoxide within 13 min with high
      sensitivity, high selectivity, over a wide pH range, and through confirmation
      with a xanthine/xanthine oxidase biochemical assay (lambdaem =439 nm). A study in
      the RAW 264.7 macrophage living cells also shows that HemiSe is not toxic, cell
      permeable (experimental log P=2.11); confocal imaging results show that HemiSe
      can detect O2 .- in endogenous and exogeneous systems.

PMID- 30300961
TI  - Periodontitis is associated with incident chronic liver disease-A population
      based cohort study.
AB  - BACKGROUND & AIMS: Chronic liver disease is a major health concern worldwide and
      the identification of novel modifiable risk factors may benefit subjects at risk.
      Few studies have analyzed periodontitis as a risk factor for liver complications.
      We studied whether periodontitis is associated with incident severe liver
      disease. METHODS: The study comprised 6165 individuals without baseline liver
      disease who participated in the Finnish population-based Health 2000 Survey
      (BRIF8901) during 2000-2001, a nationally representative cohort. Follow-up was
      until 2013 for liver-related admissions, liver cancer and mortality from National
      Hospital Discharge, Finnish Cancer Registry and Causes of Death Register,
      Statistics Finland. Mild to moderate periodontitis was defined as >=1 tooth with
      periodontal pocket >=4 mm deep, and advanced periodontitis as >=5 teeth with such
      pockets. Multiple confounders were considered. RESULTS: A total of 79 subjects
      experienced a severe liver event during follow-up. When adjusted for age, sex and
      number of teeth, hazards ratios by Cox regression regarding incident severe liver
      disease were, for mild to moderate periodontitis, 2.12 (95% CI 0.98-4.58), and,
      for advanced periodontitis, 3.69 (95% CI 1.79-7.60). These risk estimates
      remained stable after additionally adjusting for alcohol use, smoking, metabolic
      risk, serum gamma-glutamyltransferase, dental-care habits, lifestyle and
      socioeconomic status. Periodontal disease-associated liver risk was accentuated
      among subjects with non-alcoholic fatty liver disease or heavy alcohol use at
      baseline. CONCLUSIONS: Periodontitis was associated with incident liver disease
      in the general population independently of various confounders. As a preventable
      disease, periodontal disease might present a modifiable risk factor for chronic
      liver disease.

PMID- 30300962
TI  - Structural Design of Ionic Liquids for Optimizing Aromatic Dissolution.
AB  - Certain protic ionic liquids (PILs) are potentially low-cost, high-efficiency
      solvents for the extraction and processing of aromatic compounds. To understand
      the key design features of PILs that determine solubility selectivity at the
      atomic level, neutron diffraction was used to compare the bulk structure of two
      PILs with and without an aromatic solute, guaiacol (2-methoxyphenol). Guaiacol is
      a common lignin residue in biomass processing, and a model compound for anisole-
      or phenol-based food additives and drug precursors. Although the presence of
      amphiphilic nanostructure is important to facilitate the dissolution of solute
      nonpolar moieties, the local geometry and competitive interactions between the
      polar groups of the cation, anion, and solute are found to also strongly
      influence solvation. Based on these factors, a framework is presented for the
      design of PIL structure to minimize competition and to enhance driving forces for
      the dissolution of small aromatic species.

PMID- 30300963
TI  - Impact of colonoscopic screening in Familial Colorectal Cancer Type X.
AB  - BACKGROUND: Hereditary Non-Polyposis Colorectal cancer is caused by Lynch
      Syndrome (LS; an autosomal dominant condition) or by Familial Colorectal Cancer
      Type-X (FCCTX; a condition of high family risk that fulfills Amsterdam criteria).
      The lifetime risk of developing colorectal cancer (CRC) in FCCTX family members
      is high and CRC occurs later than in LS. METHODS: To determine the impact of
      primary prevention colonoscopic screening in asymptomatic first-degree relatives
      of incident CRC cases in 20 families with FCCTX, we compared cancer incidence and
      survival in 79 males and 83 females, assumed to be at 50% risk of inheriting a
      genetic CRC susceptibility factor, who entered screening to an unscreened control
      group from the families, matched for age at entry into screening and for sex.
      RESULTS: In males, median age at entry into screening was 44.8 years, median
      follow-up 12.4 years, 12% developed CRC, and 46% died after 30 years of follow
      up. Compared to the unscreened group, relative risk of CRC was 0.27 (95%
      confidence intervals (CI) 0.10-0.71). In screened females, comparable results
      were 44.5 years at entry, 11.2 years of follow-up, 7.1% developed CRC, and 7.2%
      died after 30 years of follow-up. The relative risk of CRC compared to the
      unscreened group was 0.19 (95% CI 0.07-0.48). CONCLUSION: Primary prevention
      screening colonoscopy in asymptomatic family members significantly decreased the
      risk of CRC in FCCTX.

PMID- 30300964
TI  - A review on the use of computational methods to characterize, design, and
      optimize tissue engineering scaffolds, with a potential in 3D printing
      fabrication.
AB  - The design and fabrication of tissue engineering scaffolds is a highly complex
      process. In order to provide a proper architecture for cells to grow,
      proliferate, and differentiate to form tissues, scaffolds have to be made with
      suitable properties. However, the limited structural designs and conventional
      fabrication techniques severely cripple the improvement of scaffold properties.
      To overcome these limitations, many researchers have recently adopted
      computational methods combined with 3D printing techniques as a new approach for
      scaffold design and fabrication. This approach allows scaffolds to be designed
      and fabricated with highly complex microstructures and good control and accuracy.
      Previous works have also shown this approach to be a very useful tool to predict
      the scaffold properties and to optimize the scaffold designs with a great
      reduction of experimental iterations. As this approach combining computational
      methods and 3D printing techniques for scaffold design and fabrication has many
      advantages over the conventional trial-and-error based approach, it is imperative
      to provide a state-of-the-art review on the topic. To this end, this article
      reviews the various applications of computational methods in scaffold design and
      simulation; it also briefly reviews the application of 3D printing techniques to
      fabricate the computationally designed scaffolds. Finally, the limitations and
      future trends of this approach are discussed. Overall, this review will enable
      readers to understand the benefits of using computational methods coupled with 3D
      printing to design and fabricate scaffolds, and thus help researchers to improve
      and optimize the scaffold properties for future tissue engineering research. (c)
      2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B: Appl Biomater, 2018.

PMID- 30300965
TI  - Epac1-/- mice have elevated baseline permeability and do not respond to histamine
      as measured with dynamic contrast-enhanced magnetic resonance imaging with
      contrast agents of different molecular weights.
AB  - AIM: Epac1-/- mice, but not Epac2-/- mice have elevated baseline permeability to
      albumin. This study extends the investigations of how Epac-dependent pathways
      modulate transvascular exchange in response to the classical inflammatory agent
      histamine. It also evaluates the limitations of models of blood-to-tissue
      exchange in transgenic mice in DCE-MRI measurements. METHODS: We measured DCE-MRI
      signal intensity in masseter muscle of wt and Epac1-/- mice with established
      approaches from capillary physiology to determine how changes in blood flow and
      vascular permeability contribute to overall changes of microvascular flux. We
      used two tracers, the high molecular weight tracer (Gadomer-17, MW 17 kDa,
      apparent MW 30-35 kDa) is expected to be primarily limited by diffusion and
      therefore less dependent on changes in blood flow and the low molecular weight
      tracer (Dotarem (MW 0.56 kDa) whose transvascular exchange is determined by both
      blood flow and permeability. Paired experiments in each animal combined with
      analytical methods provided an internally consistent description of microvascular
      transport. RESULTS: Epac1-/- mice had elevated baseline permeability relative to
      wt control mice for Dotarem and Gadomer-17. In contrast to wt mice, Epac1-/- mice
      failed to increase transvascular permeability in response to histamine. Dotarem
      underestimated blood flow and vascular volume and Gadomer-17 has limited
      sensitivity in extravascular accumulation. CONCLUSION: The study suggests that
      the normal barrier loosening effect of histamine in venular microvessels do not
      function when the normal barrier tightening effect of Epac1 is already
      compromised. The study also demonstrated that the numerical analysis of DCE-MRI
      data with tracers of different molecular weight has significant limitations.

PMID- 30300966
TI  - Cucurbit[8]uril Reactivation of an Inactivated Caspase-8 Mutant Reveals
      Differentiated Enzymatic Substrate Processing.
AB  - Caspase-8 constructs featuring an N-terminal FGG sequence allow for selective
      twofold recognition by cucurbit[8]uril, which leads to an increase of the
      enzymatic activity in a cucurbit[8]uril dose-dependent manner. This
      supramolecular switching has enabled for the first time the study of the same
      caspase-8 in its two extreme states; as full monomer and as cucurbit[8]uril
      induced dimer. A mutated, fully monomeric caspase-8 (D384A), which is
      enzymatically inactive towards its natural substrate caspase-3, could be fully
      reactivated upon addition of cucurbit[8]uril. In its monomeric state caspase-8
      (D384A) still processes a small synthetic substrate, but not the natural caspase
      3 substrate, highlighting the close interplay between protein dimerization and
      active site rearrangement for substrate selectivity. The ability to switch the
      caspase-8 activity by a supramolecular system thus provides a flexible approach
      to studying the activity of a protein at different oligomerization states.

PMID- 30300967
TI  - 3D-printed polycaprolactone scaffold mixed with beta-tricalcium phosphate as a
      bone regenerative material in rabbit calvarial defects.
AB  - Defect-specific bone regeneration using 3-dimensional (3D) printing of block bone
      has been developed. Polycaprolactone (PCL) is biocompatible polymer that can be
      used as 3D scaffold. The aim of this study is to assess the biocompatibility and
      osteogenic efficacy of 3D printed PCL scaffold and to evaluate the effectiveness
      of beta-tricalcium phosphate (beta-TCP) addition in PCL scaffold. In this work,
      four circular defects (diameter: 8 mm) in rabbit calvarium were randomly assigned
      to (1) negative control (control), (2) PCL block (PCL), (3) PCL mixed with 10 wt%
      beta-TCP (PCL/beta-TCP), and (4) PCL/beta-TCP plus collagen membrane (PCL/beta
      TCP + M). Animals were euthanized at 2 (n = 5) and 8 weeks (n = 5). Results
      indicated that in micro-CT, PCL/beta-TCP + M showed the highest total augmented
      volume and new bone volume at 8 weeks, but there was no significant difference
      among four groups. Histomorphometrically, PCL, PCL/beta-TCP, and PCL/beta-TCP + M
      showed the significantly higher total augmented area compared to the control.
      PCL/beta-TCP + M showed the highest new bone area but not statistically higher
      than the control. New bone formation deep inside the scaffold was observed only
      in beta-TCP added scaffold. PCL showed high biocompatibility with great volume
      maintenance. Addition of beta-TCP to PCL seemed to increase hydrophilicity and
      osteoconductivity. Developments in 3D-printed PCL material are expected. (c) 2018
      Wiley Periodicals, Inc. J Biomed Mater Res B Part B: Appl Biomater, 2018.

PMID- 30300969
TI  - Does transanal local resection increase morbidity for subsequent total mesorectal
      excision for early rectal cancer?
AB  - AIM: Local excision is recommended for early rectal cancer (pT1). Complementary
      total mesorectal excision (cTME) is warranted when bad pathological features are
      present. The impact of a prior local resection on the outcome remains unclear.
      The aim of this study was to assess if prior local excision increases the
      morbidity of a subsequent cTME compared with primary TME. METHODS: From 2001 to
      2016 all patients who underwent TME after local excision for rectal
      adenocarcinoma were studied. All were matched (1:1) with patients who underwent
      primary TME, without neoadjuvant radiochemotherapy. The matching factors included
      age, sex, body mass index, American Society of Anesthesiologists score and type
      of surgery. Short-term morbidity and pathological examination of the resected
      specimen were compared. RESULTS: Forty-one patients were included (14 women, 34%,
      mean age 65 +/- 11 years), comprising classic transanal excision (66%) and
      transanal endoscopic microsurgery (34%), and were matched to 41 patients who had
      primary TME. cTME was significantly longer (315 min +/- 87 vs 275 min +/- 58, P =
      0.03). The overall morbidity was 48.8% in the local excision group vs 31.7% in
      the control group (P = 0.18). Surgical morbidity was 31.7% vs 26.8% (P = 0.8).
      Anastomotic related morbidity was similar (local excision 17% vs TME 14.6%, P =
      0.84) and the mean length of stay was similar (14 days) in both groups. There was
      a tendency to a worse quality of mesorectal excision in the cTME group (17% vs
      5%, P = 0.15). CONCLUSION: Local excision prior to TME for early rectal cancer
      tends to increase overall morbidity and may worsen the quality of the mesorectal
      plane but should be considered as a surgical approach in select cases.

PMID- 30300970
TI  - Continuous-flow Synthesis of Aryl Aldehydes by Pd-catalyzed Formylation of Aryl
      Bromides Using Carbon Monoxide and Hydrogen.
AB  - A continuous-flow protocol utilizing syngas (CO and H2 ) was developed for the
      palladium-catalyzed reductive carbonylation of (hetero)aryl bromides to their
      corresponding (hetero)aryl aldehydes. The optimization of temperature, pressure,
      catalyst and ligand loading, and residence time resulted in process-intensified
      flow conditions for the transformation. In addition, a key benefit of
      investigating the reaction in flow is the ability to precisely control the CO-to
      H2 stoichiometric ratio, which was identified as having a critical influence on
      yield. The protocol proceeds with low catalyst and ligand loadings: palladium
      acetate (1 mol % or below) and cataCXium A (3 mol % or below). A variety of
      (hetero)aryl bromides at a 3 mmol scale were converted to their corresponding
      (hetero)aryl aldehydes at 12 bar pressure (CO/H2 =1:3) and 120  degrees C
      reaction temperature within 45 min residence time to afford products mostly in
      good-to-excellent yields (17 examples). In particular, a successful scale-up was
      achieved over 415 min operation time for the reductive carbonylation of 2-bromo-6
      methoxynaphthalene to synthesize 3.8 g of 6-methoxy-2-naphthaldehyde in 85 %
      isolated yield. Studies were conducted to understand catalyst decomposition
      within the reactor by using inductively coupled plasma-mass spectrometry (ICP-MS)
      analysis. The palladium could easily be recovered using an aqueous nitric acid
      wash post reaction. Mechanistic aspects and the scope of the transformation are
      discussed.

PMID- 30300968
TI  - Continued reassortment of avian H6 influenza viruses from Southern China, 2014
      2016.
AB  - H6 subtype avian influenza virus (AIV) was prevalent in poultry and could
      sporadically infect humans. Here, a total of 196 novel H6 AIVs isolated from
      poultry in eight provinces of China from 2014 to 2016 were phylogenetically
      characterized. Our analysis revealed that they could be divided into two clades
      in the Asian H6 HA lineage, A/wild duck/Shantou/2853/2003(H6N2) (ST2853-like)
      (85.7%) and A/duck/Shantou/339/2000(H6N2) (ST339-like) (14.3%), in which ST2853
      like strains predominate. These novel strains belonged to the H6N6 (n = 165,
      84.2%), H6N2 (n = 30, 15.3%), and H6N3 (n = 1, 0.51%) subtypes, which could be
      classified into 36 genotypes including 12 novel genotypes described in this
      study. In particular, several strains possessed the V190 and S228 mutations in HA
      (H3 numbering), which is critical for human receptor binding and identical to the
      human-derived strain A/Taiwan/2/2013(H6N1). Furthermore, 10.3% of the H6N6
      isolates possessed the N6-?11b (59-69) deletion. In summary, we describe
      phylogenetic and molecular characterizations of H6 AIVs in southern China and
      highlight the constant prevalence of H6 AIVs in poultry as well as adaptation to
      mammalian hosts.

PMID- 30300971
TI  - Organocatalysts Derived from Unnatural alpha-Amino Acids: Scope and Applications.
AB  - The organocatalytic properties of unnatural alpha-amino acids are reviewed. Post
      translational derivatives of natural alpha-amino acids include 4-hydroxy-l
      proline and 4-amino-l-proline scaffolds, and also proline homologues. The
      activity of synthetic unnatural alpha-amino acid-based organocatalysts, such as
      beta-alkyl alanines, alanine-based phosphines, and tert-leucine derivatives, are
      reviewed herein. The organocatalytic properties of unnatural monocyclic,
      bicyclic, and tricyclic proline derivatives are also reviewed. Several families
      of these organocatalysts permit the efficient and stereoselective synthesis of
      complex natural products. Most of the reviewed organocatalysts accelerate the
      reported reactions through covalent interactions that raise the HOMO (enamine
      intermediates) or lower the LUMO (iminium intermediates).

PMID- 30300972
TI  - Hydrogen-Bonding-Assisted Supramolecular Metal Catalysis.
AB  - The process of catalyst screening and discovery still largely relies on
      traditional ligand-design approaches, which suffer from complex synthetic
      requirements and offer limited structural diversity. On the contrary,
      supramolecular chemistry offers the potential to harness multiple weak secondary
      interactions to deliver self-assembled catalysts with diverse structures or to
      orient substrates to achieve enzyme-like activity and selectivity. Herein, the
      application of hydrogen-bonding (H-bonding) interactions as a construction
      element and directing group in "supramolecular transition-metal catalysis" is
      critically reviewed and the current state-of-the-art in the field is presented. H
      bonding interactions empower structurally simple ligands to deliver complex self
      assembled catalysts, which have been found to catalyze a gamut of organic
      transformations, including hydroformylation, hydrogenation, and allylation
      reactions. As we will discuss, on many occasions, these supramolecular catalysts
      outperform their analogous covalently linked catalytic systems. The potential of
      H-bonding interactions as directing groups has recently been recognized by the
      scientific community and this Focus Review presents the role of hydrogen-bonding
      interactions in directing substrates to obtain excellent selectivities and
      activities in a range of catalytic transformations.

PMID- 30300973
TI  - Reply to 'Incidence, risk factors, and prevention of stoma site incisional
      hernias: a systematic review and meta-analysis'.

PMID- 30300974
TI  - Gene Discovery in Gelsemium Highlights Conserved Gene Clusters in Monoterpene
      Indole Alkaloid Biosynthesis.
AB  - Genome mining is a routine technique in microbes for discovering biosynthetic
      pathways. In plants, however, genomic information is not commonly used to
      identify novel biosynthesis genes. Here, we present the genome of the medicinal
      plant and oxindole monoterpene indole alkaloid (MIA) producer Gelsemium
      sempervirens (Gelsemiaceae). A gene cluster from Catharanthus roseus, which is
      utilized at least six enzymatic steps downstream from the last common
      intermediate shared between the two plant alkaloid types, is found in G.
      sempervirens, although the corresponding enzymes act on entirely different
      substrates. This study provides insights into the common genomic context of MIA
      pathways and is an important milestone in the further elucidation of the
      Gelsemium oxindole alkaloid pathway.

PMID- 30300975
TI  - High-Voltage and Low-Temperature Aqueous Supercapacitor Enabled by "Water-in
      Imidazolium Chloride" Electrolytes.
AB  - Symmetric aqueous high voltage supercapacitors up to 3 V have been demonstrated
      using concentrated aqueous 1-butyl-3-methylimidazolium chloride ([BMIm]Cl),
      namely, "water-in-imidazolium chloride", as working electrolytes, and graphene
      nanoplatelets-coated carbon paper as electrodes. Performance enhancement was
      further achieved either through adding redox species such as 4-hydroxy-2,2,6,6
      tetramethylpiperidin-1-oxyl (4hT) into the electrolytes (110 Wh kg-1 for a 20 m
      [BMIm]Cl/H2 O with 0.1 m 4hT) or by pre-inserting ClO4 - anions into the graphene
      platelets. Moreover, the newly studied aqueous electrolytes allow low-temperature
      operation at -20  degrees C and even at -32  degrees C, retaining competitive
      energy storage capability (maximum energy densities of 36 and 21 Wh kg-1 ,
      respectively).

PMID- 30300976
TI  - In Situ-Fabricated 2D/2D Heterojunctions of Ultrathin SiC/Reduced Graphene Oxide
      Nanosheets for Efficient CO2 Photoreduction with High CH4 Selectivity.
AB  - Photoreduction of CO2 into fuel molecules such as CH4 represents a promising
      route to simultaneously explore renewable energy and alleviate global warming.
      However, the implementation of such a process is hampered by low product yields
      and poor selectivity. A 2D/2D heterojunction of ultrathin SiC and reduced
      graphene oxide (RGO) nanosheets was fabricated in situ for efficient and
      selective photoreduction of CO2 . Ultrathin SiC suppresses significant charge
      recombination in the bulk phase, thus providing more energetic electrons. The
      robust 2D/2D heterojunction allows fast transfer of energetic electrons from SiC
      to RGO. Combining the vital role of RGO in facilitating CO2 activation, the
      optimized SiC/RGO exhibits an electron-transfer rate of 58.17 MUmol h-1  g-1
      towards CO2 reduction, 2.7 times that of pure SiC (20.25 MUmol h-1  g-1 ). About
      92 % of the transferred electrons from SiC are devoted to generating CH4 (6.72
      MUmol h-1  g-1 ). Such high efficiency and selectivity are mainly a result of the
      densely accumulated energetic electrons within RGO, which facilitate the eight
      electron process to produce CH4 . This work will inspire the design of
      catalyst/cocatalyst systems for efficient and selective photoreduction of CO2 .

PMID- 30300977
TI  - The Current State of Evidence on Bundled Payments.
AB  - A review of the evidence shows that bundled payments for surgical procedures can
      generate savings without adversely affecting patient outcomes. Less is known
      about the effect of bundled payments for chronic medical conditions, but early
      evidence suggests that cost and quality improvements may be small or non
      existent. There is little evidence that bundles reduce access and equity, but
      continued monitoring is required.

PMID- 30300978
TI  - A Novel Approach for Incisionless Stone Management: Transpapillary Lumen-Apposing
      Metal Stent for Duct Clearance and Cholangioscopy Access.

PMID- 30300979
TI  - A Rare Case of Lymph Node Metastasis from Early Gastric Cancer.
AB  - Gastric cancers that fulfill the Japanese criteria for curative endoscopic
      resection show a low risk of lymph node (LN) metastasis. Here, we report a case
      of LN metastasis from early gastric cancer that fulfilled the curative criteria.
      A 74-year-old Japanese woman was referred to our hospital for treatment of early
      gastric cancer identified at the site of a hyperplastic polyp that had been
      diagnosed 10 years prior to presentation. Contrast-enhanced computed tomography
      did not show any lymphadenopathy and laparoscopy-assisted distal gastrectomy was
      performed. Histopathological examination revealed a predominantly moderately
      differentiated adenocarcinoma that measured 15 mm in size and was confined to the
      mucosa. However, a single metastatic regional LN was observed. A few cancer cells
      showed positive staining for alpha-fetoprotein. It should be noted that early
      gastric cancer can be accompanied by LN metastasis even if it fulfills the
      criteria for curative endoscopic resection.

PMID- 30300980
TI  - Buried Barrett's Esophagus with High-Grade Dysplasia after Radiofrequency
      Ablation.
AB  - Radiofrequency ablation therapy is an effective endoscopic option for the
      eradication of Barrett's esophagus that appears to reduce the risk of esophageal
      cancer. A concern associated with this technique is the development of
      subsquamous/buried intestinal metaplasia, whose clinical relevance and malignant
      potential have not yet been fully elucidated. Fewer than 20 cases of subsquamous
      neoplasia after the successful radiofrequency ablation of Barrett's esophagus
      have been reported to date. Here, we describe a new case of subsquamous neoplasia
      (high-grade dysplasia) following radiofrequency ablation that was managed with
      endoscopic resection. Our experience suggests that a meticulous endoscopic
      inspection prior to and after radiofrequency ablation is fundamental to reduce
      the risk of buried neoplasia development.

PMID- 30300981
TI  - Omental Patching and Purse-String Endosuture Closure after Endoscopic Full
      Thickness Resection in Patients with Gastric Gastrointestinal Stromal Tumors.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract, primarily arising from the stomach. With the
      widespread utilization of and technical advancements in endoscopy, gastric GISTs
      are being increasingly detected at an early stage, enabling complete endoscopic
      resection. Endoscopic full-thickness resection (EFTR) is an advanced technique
      that has been recognized as a treatment tool for neoplasms in the digestive tract
      in selected patients. Although a number of methods are available, closing large
      iatrogenic defects after EFTR can be a concern in clinical practice. If this
      potential problem is appropriately solved, patients with gastric GISTs would be
      suitable candidates for resection utilizing this technique. To our knowledge,
      this is the first study to propose omental patching and purse-string endosuture
      closure following EFTR as a feasible endoscopic option in patients with gastric
      GISTs.

PMID- 30300982
TI  - Primary Gastric Small Cell Carcinoma (Presenting as Linitis Plastica) Diagnosed
      Using Endoscopic Ultrasound-Guided Biopsy: A Case Report.
AB  - Small cell carcinomas are the most aggressive, highly malignant neuroendocrine
      tumors; among these, gastric small cell carcinoma (GSCC) is extremely rare. Here
      we report a case of a patient with primary GSCC, presenting as linitis plastic,
      who was diagnosed using endoscopic ultrasound (EUS)-guided biopsy. With
      undiagnosed linitis plastica, an 80-year-old woman was referred to our
      institution. Abdominal computed tomography revealed irregular wall thickening
      extending from the gastric body to the antrum. Endoscopy suspected to have
      Borrmann type IV advanced gastric cancer. EUS of the stomach showed diffuse
      submucosal thickening of the gastric wall, mainly the antrum. EUS-guided bite-on
      bite biopsy confirmed the diagnosis of GSCC. In general, GSCC is difficult to
      diagnose and careful examination is necessary to determine the therapeutic
      strategy; however, EUS is particularly helpful in the differential diagnosis of a
      lesion presenting as linitis plastica.

PMID- 30300983
TI  - Single-Stage Endoscopic Stone Extraction and Cholecystectomy during the Same
      Hospitalization.
AB  - Background/Aims: The clinical impact of single-stage endoscopic stone extraction
      by endoscopic retrograde cholangiopancreatography (ERCP) and cholecystectomy
      during the same hospitalization remains elusive. This study aimed to determine
      the efficacy and safety of single-stage ERCP and cholecystectomy during the same
      hospitalization in patients with cholangitis. Methods: We retrospectively
      reviewed the medical records of 166 patients who underwent ERCP for mild to
      moderate cholangitis due to choledocholithiasis secondary to cholecystolithiasis
      from 2012 to 2016. Results: Complete stone extraction was accomplished in 92% of
      patients (152/166) at the first ERCP. Among 152 patients who underwent complete
      stone extraction, cholecystectomy was scheduled for 119 patients (78%).
      Cholecystectomy was performed during the same hospitalization in 89% of patients
      (106/119). We compared two groups of patients: those who underwent
      cholecystectomy during the same hospitalization (n=106) and those who underwent
      cholecystectomy during a subsequent hospitalization (n=13). In the delayed group,
      cholecystectomy was performed about three months after the first ERCP. There were
      no significant differences between the groups in terms of operative time, rate of
      postoperative complications, and interval from cholecystectomy to discharge.
      Conclusions: Single-stage endoscopic stone extraction is recommended in patients
      with mild to moderate acute cholangitis due to choledocholithiasis. The
      combination of endoscopic stone extraction and cholecystectomy during the same
      hospitalization is safe and feasible.

PMID- 30300984
TI  - Endoscopy Timing in Patients with Acute Upper Gastrointestinal Bleeding.
AB  - Background/Aims: The role of very early (<=12 hours) endoscopy in nonvariceal
      upper gastrointestinal bleeding is controversial. We aimed to compare results of
      very early and early (12-24 hours) endoscopy in patients with upper
      gastrointestinal bleeding demonstrating low-risk versus high-risk features and
      nonvariceal versus variceal bleeding. Methods: : This retrospective study
      included patients with nonvariceal and variceal upper gastrointestinal bleeding.
      The primary outcome was a composite of inpatient death, rebleeding, or need for
      surgery or intensive care unit admission. Endoscopy timing was defined as very
      early and early. We performed the analysis in two subgroups: (1) high-risk vs.
      low-risk patients and (2) variceal vs. nonvariceal bleeding. Results: : A total
      of 102 patients were included, of whom 59.8% underwent urgent endoscopy. Patients
      who underwent very early endoscopy received endoscopic therapy more frequently
      (p=0.001), but there was no improvement in other clinical outcomes. Furthermore,
      patients at low risk and with nonvariceal bleeding who underwent very early
      endoscopy had a higher risk of the composite outcome. Conclusion: s: Very early
      endoscopy does not seem to be associated with improved clinical outcomes and may
      lead to poorer outcomes in specific populations with upper gastrointestinal
      bleeding. The actual benefit of very early endoscopy remains controversial and
      should be further clarified.

PMID- 30300985
TI  - Bimodal Chromoendoscopy with Confocal Laser Endomicroscopy for the Detection of
      Early Esophageal Squamous Cell Neoplasms.
AB  - Background/Aims: This study aimed to evaluate the diagnostic accuracy of dual
      focus narrow-band imaging (dNBI) and Lugol'schromoendoscopy (LCE) combined with
      probe-based confocal laser endomicroscopy (pCLE) to screen for esophageal
      squamous cell neoplasms (ESCNs) in patients with a history of head and neck
      cancer. Methods: From March to August 2016, dNBI was performed. Next, LCE was
      performed, followed by pCLE and biopsy. Histology has historically been the gold
      standard to diagnose ESCN. The sensitivity, specificity, positive predictive
      value (PPV), negative predictive value (NPV), and accuracy of dNBI and LCE
      adjunct with pCLE were determined. Results: Twenty-four patients were included.
      Ten ESCNs were found in 8 patients (33%). Forty percent of high-graded
      intraepithelial neoplasias and all low-grade intraepithelial neoplasias were
      overlooked by dNBI. The sensitivity, specificity, PPV, NPV, and accuracy of dNBI
      vs. LCE combined with pCLE were 50% vs. 80%, 62% vs. 67%, 36% vs. 44%, 75% vs.
      91%, and 83% vs. 70%, respectively. Conclusions: The use of dNBI to detect ESCN
      was suboptimal. LCE with pCLE following dNBI had additional value for detecting
      esophageal dysplasia not detected by dNBI. The use of pCLE to detect dNBI-missed
      lesions yielded a high NPV, while pCLE-guided biopsy could reduce the number of
      unnecessary biopsies.

PMID- 30300987
TI  - Intussusception after Colonoscopy: A Case Report and Review of Literature.
AB  - Intussusception after colonoscopy is an unusual complication. A MEDLINE search
      revealed only 7 reported cases. We present a report of a 28-year-old man who
      developed abdominal pain several hours after routine colonoscopy and in whom
      computed tomography (CT) revealed colocolic intussusception. We postulate that
      this condition is iatrogenic and induced by suctioning of gas on withdrawal of
      the colonoscope. A common observation among the reported cases was abdominal pain
      several hours after colonoscopy and right-sided intussusception. All cases had
      colonoscopy reaching the right side of the colon. Treatment for adult
      intussusception remains controversial with regard to reduction versus resection,
      especially given the high association with a pathological cause and malignancy.
      Among the 8 reported cases, only the current case did not require surgery. A
      combination of benign colonoscopy, CT, and the clinical picture should provide
      sufficient information to initially choose a more conservative treatment
      approach.

PMID- 30300986
TI  - First Characterization with Ultrasound Contrast Agent of a Fibrovascular Polyp
      Before Its Endoscopic Resection: A Case Report (with Videos).
AB  - We described for the first time the contrast enhancement of a giant fibrovascular
      esophageal polyp using ultrasound contrast agent, Sonovue(r) (Bracco, Milan,
      Italy) during echoendoscopy. Fine Doppler was unsuccessful in showing
      vascularization due to the mobile characteristic of the tumor. In contrast, via
      Sonovue(r) , tissue microcirculation was highlighted inside the entire head of
      the polyp, leading to better appreciate the risk of bleeding related to its
      resection. In a second part, we showed the feasibility of classic polypectomy for
      this giant polyp (5*5 cm) without complication and results of control endoscopy
      at 3 months. The present case is summarized in a video.

PMID- 30300988
TI  - Mucosal Changes in the Small Intestines in Portal Hypertension: First Study Using
      the Pillcam SB3 Capsule Endoscopy System.
AB  - BACKGROUND/AIMS: To evaluate patients with portal hypertension (PH) of varied
      etiologies for portal hypertensive enteropathy (PHE) using the PillCam SB3
      capsule endoscopy (CE) system. METHODS: Consecutive patients with PH presenting
      with unexplained anemia and/or occult gastrointestinal bleeding were evaluated
      using the PillCam SB3 CE system. Abnormal findings were categorized as vascular
      or non-vascular. The patients with ongoing bleeding caused by PHE were treated.
      The correlation of the CE scores of PHE with the clinical, laboratory, and
      endoscopic features was determined. RESULTS: Of the 43 patients included in the
      study, 41 (95.3%) showed PHE findings. These included varices (67.4%), red spots
      (60.5%), erythema (44.2%), villous edema (46.5%), telangiectasia (16.3%), and
      polyps (16.3%). The CE scores varied from 0 to 8 (mean+/-standard deviation,
      4.09+/-1.8). Five patients (11.6%) showed evidence of ongoing or recent bleeding
      due to PHE. Three of these five patients underwent endotherapy, and one patient
      underwent radiological coil placement. CONCLUSION: The PillCam SB3 CE system
      revealed a high prevalence of PHE in the patients with PH. Using this system,
      evidence of bleeding due to PHE was found in a small but definite proportion of
      the patients.

PMID- 30300989
TI  - Renovations Needed: the FDA's Floor/Ceiling Framework, Preemption, and the Opioid
      Epidemic.
AB  - The FDA's regulatory framework for pharmaceuticals uses a "floor/ceiling" model:
      administrative rules set a "floor" of minimum safety, while state tort liability
      sets a "ceiling" of maximum protection. This model emphasizes pre-market scrutiny
      but largely relies on the state common law "ceiling" to police the postapproval
      drug market. As the Supreme Court increasingly holds state tort law preempted by
      federal administrative standards, the FDA's framework becomes increasingly
      imbalanced. In the face of a historic prescription medication overdose crisis,
      the Opioid Epidemic, this imbalance allows the pharmaceutical industry to avoid
      internalizing the public health costs of their opioid products. This Note argues
      that the FDA's administrative design misallocates the costs of the Opioid
      Epidemic and fails to adequately compensate those injured by it. Part I
      summarizes the FDA's regulatory framework with respect to opioid medications.
      Part II explains how that framework creates a compensatory problem that prevents
      the internalization of negative externalities by pharmaceutical manufacturers.
      Part III proposes a victims' compensation fund as the best substitute for the
      functions long performed by state tort liability.

PMID- 30300990
TI  - Fatigue and weakness hinder patient social reintegration after liver
      transplantation.
AB  - Background/Aims: With improvements in the survival of liver transplantation (LT)
      recipients, the focus is shifting to patient quality of life (QOL), and
      employment is an important factor in aiding the social reintegration of LT
      patients. This study aims to evaluate the current employment status of liver
      graft recipients and various factors that may hinder reemployment. Methods: Fifty
      patients above age 18 who underwent either living or deceased donor LT at a
      single center from March 2009 to July 2016 were interviewed during their visit to
      the outpatient clinic. The internally developed questionnaire consisted of 10
      items. The Karnofsky Performance Scale and EQ-5D were used to evaluate patient
      function and QOL. Results: A total of 25 (50%) patients returned to work after
      transplantation (the working group), and 21 (84%) patients in the working group
      returned to work within the first year after transplantation. In the non-working
      group (n=25), 17 (68%) answered that their health was the reason for
      unemployment. Fatigue and weakness were the most frequent symptoms. Conclusions:
      The data shows that as many as 50% of total patients returned to work after
      receiving LT. Fatigue and weakness were the most common complaints of the
      unemployed group, and resolving the causes of these symptoms may help to increase
      the employment rate.

PMID- 30300991
TI  - Pathologic differential diagnosis of metastatic carcinoma in the liver.
AB  - The liver is one of the most common sites to which malignancies preferentially
      metastasize. Although a substantial number of liver malignancies are primary
      tumors, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma,
      the metastasis of carcinomas to the liver is relatively common and frequently
      encountered in clinical settings. Representative carcinomas that frequently
      metastasize to the liver include colorectal carcinoma, breast carcinoma,
      neuroendocrine tumors, lung carcinoma, and gastric carcinoma. The diagnostic
      confirmation of suspected metastatic lesions in the liver is generally achieved
      through a histopathologic examination of biopsy tissues. Although morphology is
      the most important feature for a pathologic differential diagnosis of metastatic
      carcinomas, immunohistochemical studies facilitate the differentiation of
      metastatic carcinoma origins and subtypes. Useful immunohistochemical markers for
      the differential diagnosis of metastatic carcinomas in the liver include
      cytokeratins (CK7, CK19, and CK20), neuroendocrine markers (CD56, synaptophysin,
      and chromogranin A), and tissue-specific markers (CDX2, SATB2, TTF-1, GCDFP-15,
      mammaglobin, etc.). Here, we provide a brief review about the pathologic
      differential diagnosis of major metastatic carcinomas in the liver.

PMID- 30300992
TI  - Metal concentrations in the beach sediments of Bahia Solano and Nuqui along the
      Pacific coast of Choco, Colombia: A baseline study.
AB  - Thirty sediment samples from four different beaches along Bahia Solano and Nuqui
      (Department of Choco) of eastern Colombia, with tourism and gold mining
      activities, were analysed to estimate the concentrations of fourteen different
      acid leachable metals. Metal distribution patterns showed elevated concentrations
      of Co, Cr, Cu, Pb and Zn compared with the upper continental crust values.
      Calculation of geochemical indices confirmed that the enrichment is due to
      periodic gold mining activities (severe to extremely severe enrichment of Cu, Zn,
      V, Co, Cr and Pb) along with natural (geological) contributions (minor and
      moderate enrichment of Ca, Mg, Fe, Ti, Mn and Li). Potential ecological risk
      index revealed that Pb posed the highest risk. Our results together with a global
      comparison suggest that the observed metal enrichments are mainly caused by
      mining and to a lesser extent by tourism in this region, thus instigating
      continuous monitoring of metal concentrations in this region.

PMID- 30300993
TI  - Marine benthic communities affected by the Doce River (southwestern Atlantic):
      Baseline before a mining disaster.
AB  - Prior to Brazil's worst environmental disaster, caused by a mining dam collapse,
      we had carried out a study of the marine benthic macrofauna (11-51 m depth) under
      the influence of the Doce River. Our results showed significant diversity, in
      which mollusks, polychaetes, and crustaceans had the highest frequency, density,
      and abundance, represented by 162 families in summer and 173 in winter. Our
      results suggested that richness, abundance, and diversity increase with distance
      from the coast. Furthermore, with increasing distance from the coast and river
      mouth, in addition to increasing depth, there was a differentiation in
      composition and abundance. Multivariate analyses showed depth, carbonate, and
      organic matter as important factors that explain variations in composition and
      diversity across the continental shelf. The results could provide an invaluable
      baseline for measuring the effects on shallow and mesophotic communities of one
      of the largest tailings dam failures worldwide.

PMID- 30300994
TI  - The distribution of and biodegradation impact on spilled oil in sediments from
      Dalian Bay, NE China.
AB  - Three cores collected in the area of 16th July 2010 oil spill by box crab in May
      2013 and July 2014 at the Dalian Bay have been geochemically characterized to
      investigate the fate of chemical components in sediments. The total organic
      carbon, extractable organic matter contents and biomarker compositions have been
      applied for the differentiation of alien organic matters from in situ ones and
      evaluation of the biodegradation impact. Multivariate statistical analysis
      suggests four groups of sediments. Except a few samples at deepest part of BQ050,
      majority samples have certain affinity with the spilled oil. The most
      contaminated sediments occur at site BQ050 and the spilled oil has migrated to 8
      12 cm depth. The degree of contamination can be ranked by the similarity of
      molecular compositions with spilled oil. Variable biomarker components in
      sediment extracts were also altered by ongoing biodegradation.

PMID- 30300995
TI  - A study of the environmental factors influencing the growth phases of Ulva
      prolifera in the southern Yellow Sea, China.
AB  - Macroalgal blooms of U. prolifera in the southern Yellow Sea (SYS) have become an
      ecological disaster. In this study, we attempt to explore the influence of
      environmental factors and human activity on the annual development of U.
      prolifera during 2011-2016, combining geostationary ocean color imager images and
      monitored environmental factors. Blooms of U. prolifera were mainly distributed
      in the central SYS, drifting from the southern Yellow Sea Radial Sand Ridges.
      Three growth phases were defined (initial phase, outbreak phase and dissipation
      phase) to facilitate analysis of the relationship between the environmental
      factors and growth conditions of U. prolifera. Seaweed cultivation, sea surface
      temperature (SST) and available radiation influenced the algal biomass during the
      initial phase; the seawater transparency, precipitation and wind activity
      affected the algae during the outbreak phase; and SST, intense radiation and
      cleanup operations increased the rate of algal extinction in the dissipation
      phase.

PMID- 30300996
TI  - Long-term variations and influence factors of nutrients in the western North
      Yellow Sea, China.
AB  - This study investigated the long-term variations and compositions of nutrients
      and the associated controlling factors in the western North Yellow Sea on the
      basis of historical data. The NO3-N and DIN concentrations and N/P showed
      continuous increases over the past two decades, which were dominantly affected by
      riverine inputs, such as inputs from the Yellow River, Yalujiang River and Jia
      River and atmospheric deposition. However, due to human activities, such as dam
      construction in rivers and climate change, the SiO3-Si concentrations and Si/P
      ratios decreased before the early 1990s and then gradually increased. The
      vertical distributions of nutrients displayed higher concentrations at the bottom
      than those at the surface in summer, which was attributed to the combined
      influence of the thermocline, the Yellow Sea Cold Water Mass, the Yellow Sea Warm
      Current and biological activities.

PMID- 30300997
TI  - Distribution and enrichment of trace metals in surface marine sediments collected
      by the manned submersible Jiaolong in the Yap Trench, northwest Pacific Ocean.
AB  - In this study, we carried out grain size and heavy metal analyses and also
      assessed heavy metal enrichment and ecological risk indices in ten sediment
      samples collected by the manned submersible Jiaolong at different segments of the
      Yap Trench. The results showed that the sediments in the Yap Trench were mainly
      slumping deposits composed of sandy silt. Heavy metals in the sediments showed
      different spatial distribution patterns from north to south direction of the
      trench. The distribution pattern of these heavy metals also differed in the
      eastern and western flanks of the trench. From the results of the enrichment
      factors, only arsenic, chromium, and manganese showed a slight enrichment.
      However, all elements were affected by natural factors. Further, most elements
      showed a low ecological risk, and only arsenic showed a moderate risk at two
      stations. Finally, the potential ecological risk of the whole study area was at a
      low level.

PMID- 30300998
TI  - Mapping widespread and increasing underwater noise pollution from acoustic
      deterrent devices.
AB  - Acoustic deterrent devices (ADDs) are used in attempts to mitigate pinniped
      depredation on aquaculture sites through the emission of loud and pervasive
      noise. This study quantified spatio-temporal changes in underwater ADD noise
      detections along western Scotland over 11 years. Acoustic point data ('listening
      events') collected during cetacean line-transect surveys were used to map ADD
      presence between 2006 and 2016. A total of 19,601 listening events occurred along
      the Scottish west coast, and ADD presence was recorded during 1371 listening
      events. Results indicated a steady increase in ADD detections from 2006 (0.05%)
      to 2016 (6.8%), with the highest number of detections in 2013 (12.6%), as well as
      substantial geographic expansion. This study demonstrates that ADDs are a
      significant and chronic source of underwater noise on the Scottish west coast
      with potential adverse impacts on target (pinniped) and non-target (e.g.
      cetaceans) species, which requires further study and improved monitoring and
      regulatory strategies.

PMID- 30300999
TI  - Plastic levels in sediments closed to Cecina river estuary (Tuscany, Italy).
AB  - This study focuses on plastic distribution levels (shape, size, colour, type) in
      sediments from the coastal area of Cecina (Tuscany, Italy). Samples are collected
      in three sampling stations along six transect settled randomly along the
      shoreline and along the final tract of the Cecina river. Recorded plastic size
      ranges within 62.51-13,462 MUm (average values 1591 +/- 837 MUm). Microplastics
      (<5000 MUm) represent over than 97% of the total even if mesoplastics (5000
      25,000 MUm) are also recorded (2%). Over than 60% of recorded plastic items are
      higher than 500 MUm. Measured levels range within 72 (ST2)-191 (ST4) items/kg
      d.w. Fragment > Fiber > Granule in each of the tested sampling site. Plastic
      litter levels recorded in study evidence low pollution compared to the existing
      literature supporting the occurrence of good environmental levels in Cecina
      coastline for the "Marine litter" descriptor.

PMID- 30301000
TI  - Baseline radionuclide concentration in selected marine organisms around the
      coastal areas of Ratnagiri and Sindhudurg districts, west coast of Maharashtra,
      India.
AB  - The present work deals with assessment of baseline radionuclide concentration in
      marine organisms around selected coasts of Maharashtra, India. This baseline
      study highlights concentrations of natural and fallout radionuclides in finfish
      and shellfish species found in the surrounding seawater. Water and fish samples
      were collected, processed, and analyzed for 238U, 226Ra, 228Ra, 232Th, 40K, and
      137Cs by high-resolution gamma spectrometry. 238U, 226Ra, 228Ra, 232Th, 40K, and
      137Cs concentrations were found to be in the range of <=1.5, <=2.0, <=0.4, <=1.5,
      <=8.0 to 258, and <=0.2 Bq/kg, respectively. The seasonal study revealed the
      maximum concentration in premonsoon season. Activity concentrations were higher
      in pelagic fish than those in demersal fish. A higher concentration factor was
      reported in shellfish than in finfish.

PMID- 30301001
TI  - Long term development of Bathing Water Quality at the German Baltic coast:
      spatial patterns, problems and model simulations.
AB  - Bathing water quality plays a key role for public health, is highly important for
      recreational tourism and therefore monitored in the EU-Directive 2006/7/EC. To
      identify pollution hot spots, sources and impacts of the directive-change in
      2006, including a change of indicator organisms, we evaluated monitoring data of
      the past 15 years, collected own data, determined survival rates of indicator
      organisms and applied hydrodynamic modelling in a micro-tidal-system. Due to
      higher survival rates under turbid conditions and restricted water exchange,
      shallow, eutrophic bays and lagoons are hot spots of microbial pollution. Rain
      events cause high microbial emission and distribution. Based on different decay
      rates, the ratio of E. coli to Enterococci can hint towards a pollution source.
      Including rain predictions, currents and winds, hydrodynamic models can then
      assess the daily risk of microbial pollution at each bathing site. They are an
      important tool to modify beach management and event-based monitoring.

PMID- 30301003
TI  - Bioaccumulation of 2,4,6-trinitrotoluene (TNT) and its metabolites leaking from
      corroded munition in transplanted blue mussels (M. edulis).
AB  - Bioaccumulation of 2,4,6-trinitrotoluene (TNT) and its main metabolites 2-amino
      4,6-dinitrotoluene (2-ADNT) and 4-amino-2,6-dinitrotoluene (4-ADNT) leaking from
      corroded munitions at a munitions dumping site (Kolberger Heide, Germany) was
      evaluated in transplanted blue mussels (Mytilus edulis). Six moorings with mussel
      bags were placed east and west at varying positions near the mine mound. In order
      to monitor any differences resulting from changing seasons, three exposure times
      were chosen. First exposure period: April-July 2016 (106 days); second exposure
      period: July-December 2016 (146 days); third exposure period: December 2016-March
      2017 (92 days). We found amounts of 4-ADNT in mussel tissue ranging from 2.40 +/-
      2.13 to 7.76 +/- 1.97 ng/(g mussel wet weight). Neither TNT nor 2-ADNT could be
      detected. Considering seasonal differences, orientation and distances of the
      moorings to the mine mound no correlation between levels in mussel tissue was
      evident.

PMID- 30301002
TI  - Comparative feeding rates of native and invasive ascidians.
AB  - Ascidians have a recent history of species introductions globally, often with
      strong ecological impacts. Comparisons of per capita effects of invaders and
      comparable natives are useful to assess such impacts. Here, we explore ingestion
      rates (IR) and clearance rates (CR) of Ciona intestinalis and Ciona robusta, co
      occurring native and non-native ascidians, respectively, from Brittany, France.
      IR was positively related to food concentration, with the invader responding more
      strongly to increasing food concentration. CR also differed by species, with the
      invader demonstrating higher values. C. robusta exhibited a higher functional
      response (Type I) than did C. intestinalis (Type II). Relative impact measured
      using seasonal abundance and IR revealed that C. robusta has a much greater
      impact than C. intestinalis at all food concentrations tested, though the former
      has a constrained distribution which limits its regional impact. Nevertheless,
      when abundant, we expect C. robusta to exert a greater impact on algal foods.

PMID- 30301004
TI  - Screening of human and veterinary pharmaceuticals in estuarine waters: A baseline
      assessment for the Tejo estuary.
AB  - We investigated the presence of 66 human and veterinary pharmaceuticals from
      seven therapeutic groups in surface waters of the Tejo estuary. Collection sites
      covered the entire estuary and included areas near main river inflows and
      wastewater treatment outfalls, traversing urban, agriculture, aquaculture, and
      nature reserve areas. Detection of pharmaceuticals was performed via UHPLC-TOF
      MS. Pharmaceuticals were found in all sites (32 different compounds in total).
      Antibiotics, beta-blockers, antihypertensives and anti-inflammatories were the
      most frequently detected (>90%), with variation in concentrations reflecting the
      multifaceted nature of estuarine surroundings (accumulated site contamination
      between 15 and 351 ng L-1). Higher concentrations of antidepressant Sertraline
      (304 ng L-1), non-steroidal anti-inflammatory Diclofenac (51.8 ng L-1), lipid
      regulator Gemfibrozil (77.0 ng L-1), antihypertensive Ibersartan (161.9 ng L-1)
      or antibiotic Doxycycline (128.0 ng L-1), among others, though localized may
      potentially impact key estuarine functions or services. Ultimately, results
      provide a baseline for regulatory information and future biota evaluations.

PMID- 30301005
TI  - Thalassia testudinum as a potential vector for incorporating microplastics into
      benthic marine food webs.
AB  - Seagrasses are among the most productive shallow water ecosystems, serving a
      diverse assemblage of fish and invertebrates. Tropical seagrass communities are
      dominated by the turtle grass Thalassia testudinum, whose wide, flattened blades
      host diverse epibiont communities. Amidst its epibionts, T. testudinum may also
      be accumulating microplastics, which are a ubiquitous marine pollutant even in
      remote locales. To assess the extent of microplastic accumulation, seagrass
      samples were collected from Turneffe Atoll, which lies offshore but parallel with
      a major urban center. Seventy-five percent of Thalassia blades had encrusted
      microplastics, with microfibers occurring more than microbeads and chips by a
      ratio of 59:14. Grazers consumed seagrasses with higher densities of epibionts.
      Potential mechanisms for microplastic accumulation include entrapment by
      epibionts, or attachment via biofilms. This study is the first to document
      microplastics on marine vascular plants, suggesting that macroherbivory is a
      viable pathway for microplastic pollution to enter marine food webs.

PMID- 30301006
TI  - UV fluences required for compliance with ballast water discharge standards using
      two approved methods for algal viability assessment.
AB  - This study investigates the extra UV fluence needed to meet the International
      Maritime Organisation's ballast water discharge standards for the 10-50 MUm size
      class using the approved vital stain (VS) method compared to the Most Probable
      Number (MPN) method for organism viability assessment. Low- and medium pressure
      UV collimated beam treatments were applied to natural algae collected in
      temperate and tropical water environments and analysed using both methods. About
      10 times higher UV fluence was required to meet discharge standards when using VS
      compared to MPN. Implementing a dark-hold period after UV treatments decreased
      algal viability. Length of dark-hold period to meet discharge standards decreased
      with increasing UV fluence. No significant differences between temperate and
      tropical samples were observed. The results showed that UV treated algae assessed
      using the VS method could meet discharge standards by increasing fluence and/or
      introducing a dark-hold period.

PMID- 30301007
TI  - Biochemical and molecular responses in oysters Crassostrea brasiliana collected
      from estuarine aquaculture areas in Southern Brazil.
AB  - Biochemical and molecular responses were evaluated in oysters Crassostrea
      brasiliana collected from three oyster farms, at Guaratuba Bay, southern Brazil,
      forming a pollutant gradient: Farm 1 (reference site - farther from the urban
      area), Farm 2 (intermediate site) and Farm 3 (nearest to the urban area).
      Oxidative stress markers, DNA damage and transcript levels of CYP2AU1, CYP2
      like1, CYP2-like2, SULT-like, GPx-like, SOD-like, CAT-like, GSTmicrosomal-like,
      GSTomega-like, FABP-like and ALAd-like genes were analyzed in the gills. The
      levels of polycyclic aromatic hydrocarbons, linear alkylbenzenes and
      polychlorinated biphenyls were also evaluated in the soft tissues of the oysters
      and in the sediment of the Farms. Higher GSTomega-like, CYP2AU1 and FABP-like
      transcript levels, GR and G6PDH activities and lipid peroxidation levels were
      observed in oysters from Farms 2 and 3, suggesting pollutant effects on oysters.
      Alterations in oxidative stress markers also suggest a response against a
      prooxidant condition in C. brasiliana due to pollutant effects.

PMID- 30301008
TI  - Mercury concentrations in muscles and liver tissues of Cape monkfish (Lophius
      vomerinus) from the Northern Benguela, Namibia.
AB  - Cape monkfish (Lophius vomerinus) is one of the long-lived species and top
      predators in the northern Benguela region. Studies on bioaccumulation of mercury
      (Hg) in cape monkfish are limited. This study compared the total Hg concentration
      between monkfish muscle and liver tissue; and related the monkfish total Hg
      concentrations to fish body size and capture locations (depth and latitude).
      Monkfish specimens (n = 529) were collected from 2016 to 2018. The mean total Hg
      concentration was 0.126 +/- 0.005 mg/kg in muscle tissues and 0.106 +/- 0.005
      mg/kg in liver tissues. No significant differences were observed between total Hg
      concentrations of muscles and liver tissues. Differences in Hg concentrations
      between monkfish length classes were observed. No significant correlation was
      found between total Hg concentrations and latitude. A significant increase of
      total Hg concentration with the depth was observed. The concentrations of Hg were
      below the World Health Organization (WHO limits for fish (0.5 mg/kg).

PMID- 30301009
TI  - Pollution and coral damage caused by derelict fishing gear on coral reefs around
      Koh Tao, Gulf of Thailand.
AB  - Most lost fishing gear is made of non-biodegradable plastics that may sink to the
      sea floor or drift around in currents. It may remain unnoticed until it shows up
      on coral reefs, beaches and in other coastal habitats. Stony corals have fragile
      skeletons and soft tissues that can easily become damaged when they get in
      contact with lost fishing gear. During a dive survey around Koh Tao, a small
      island in the Gulf of Thailand, the impact of lost fishing gear (nets, ropes,
      cages, lines) was studied on corals representing six different growth forms:
      branching, encrusting, foliaceous, free-living, laminar, and massive. Most gear
      (>95%) contained plastic. Besides absence of damage (ND), three categories of
      coral damage were assessed: fresh tissue loss (FTL), tissue loss with algal
      growth (TLAG), and fragmentation (FR). The position of the corals in relation to
      the fishing gear was recorded as either growing underneath (Un) or on top (On),
      whereas corals adjacent to the gear (Ad) were used as controls. Nets formed the
      dominant type of lost gear, followed by ropes, lines and cages, respectively.
      Branching corals were most commonly found in contact with the gear and also
      around it. Tubastraea micranthus was the most commonly encountered coral species,
      either Un, On, or Ad. Corals underneath gear showed most damage, which
      predominantly consisted of tissue loss. Fragmentation was less common than
      expected, which may be related to the low fragility of T. micranthus as dominant
      branching species. Even if nets serve as substrate for corals, it is recommended
      to remove them from reefs, where they form a major component of the plastic
      pollution and cause damage to corals and other reef organisms.

PMID- 30301010
TI  - An ecological risk assessment model for Arctic oil spills from a subsea pipeline.
AB  - There is significant risk associated with increased oil and gas exploration
      activities in the Arctic Ocean. This paper presents a probabilistic methodology
      for Ecological Risk Assessment (ERA) of accidental oil spills in this region. A
      fugacity approach is adopted to model the fate and transport of released oil,
      taking into account the uncertainty of input variables. This assists in
      predicting the 95th percentile Predicted Exposure Concentration (PEC95%) of
      pollutants in different media. The 5th percentile Predicted No Effect
      Concentration (PNEC5%) is obtained from toxicity data for 19 species. A model
      based on Dynamic Bayesian Network (DBN) is developed to assess the ecological
      risk posed to the aquatic community. The model enables accounting for the
      occurrence likelihood of input parameters, as well as analyzing the time-variable
      risk profile caused by seasonal changes. It is observed through the results that
      previous probabilistic methods developed for ERA can be overestimating the risk
      level.

PMID- 30301011
TI  - Widespread recovery of seagrass coverage in Southwest Florida (USA): Temporal and
      spatial trends and management actions responsible for success.
AB  - In Southwest Florida, a variety of human impacts had caused widespread losses of
      seagrass coverage from historical conditions. St. Joseph Sound and Clearwater
      Harbor lost approximately 24 and 51%, respectively, of their seagrass coverage
      between 1950 and 1999, while Tampa Bay and Sarasota Bay had lost 46% and 15%,
      respectively, of their seagrass coverage between 1950 and the 1980s. However,
      over the period of 1999 to 2016, the largest of the six estuaries, Tampa Bay,
      added 408 ha of seagrass per year, while the remaining five estuaries examined in
      this paper added approximately 269 ha per year. In total, seagrass coverage in
      these six estuaries increased 12,171 ha between the 1980s and 2016. Focused
      resource management plans have held the line on nitrogen loads from non-point
      sources, allowing seagrass resources to expand in response to reductions in point
      source loads that have been implemented over the past few decades.

PMID- 30301012
TI  - Heavy metal distribution, contamination and analysis of sources - Intertidal
      zones of Sandu Bay, Ningde, China.
AB  - Concentrations of heavy metals in sediments and seawaters from the intertidal
      zone are analyzed along with cage-bred fish in the Sandu Bay of Fujian Province
      in China. Elements measured are As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn. The
      concentrations of Cu and Ni found in the sediments do not meet the first standard
      of the Chinese National Criteria for Marine Sediment Quality. The results of
      Igeo, EF, and CF index calculations for the sediment samples clearly prove
      anthropogenic causes of contamination. The water quality standard for fisheries
      was exceeded by As, Hg, and Cu. Cage-bred fish show increased levels of As, Cr,
      and Zn. Significant associations are found for AsCu and NiZn. These findings can
      be related to coal and crude oil combustion and processes associated with the
      production of batteries, steel, and alloys. The results point to industrial
      source locations along discharging rivers north and northwest of the Sandu Bay.

PMID- 30301013
TI  - Proof of concept for a model of light reflectance of plastics floating on natural
      waters.
AB  - Remote sensing of plastic littering natural waters is an emerging field of
      science with the potential to provide observations on local to global scales. We
      present the verification of a theoretical reflectance model of sunlight
      interacting with a water surface littered with buoyant plastic objects. We
      measured a few common litter items of different polymers as well as shapes,
      transparencies, and surface roughnesses. Spectral reflectance measurements in the
      field were backed up with measurements in the laboratory of coefficients of total
      and diffuse reflectance, transmittance and absorption. We evaluated a single-band
      algorithm for 850 nm wavelength and a dual-band algorithm using a second
      wavelength at a polymer absorption band between 1660 and 1730 nm. Both algorithms
      were plastic litter type specific. Our findings show that for interpreting
      spectral remote sensing of floating plastic, physical properties that control
      geometrical optics should complement information about the absorption spectra of
      the polymer.

PMID- 30301014
TI  - Decadal and spatial variation of Hg concentrations in sediments of a multi
      stressor impacted estuary.
AB  - The present study has evaluated temporal and spatial mercury trends based on
      surficial sediment samples and 210Pb-dated sediment profiles. The obtained
      results show that there are areas close to the main bay's tributary rivers where
      the Hg content has doubled during the last 15 years and regions where it has
      decreased by a factor of 2, mainly the area close to the navigation channel,
      which is submitted to periodic dredging. In the inner part of the bay, the most
      contaminated region, mercury shows a strong association with sulfide. In the same
      region, based on the 210Pb results, it was possible to calculate the yearly
      increment on the Hg concentration in the surface sediment, 0.62 MUg kg-1 y-1 to
      0.29 MUg kg-1 y-1, according to the distance to the bay's main tributary rivers.

PMID- 30301015
TI  - Numerical modelling of mercury evasion in a two-layered Adriatic Sea using a
      coupled atmosphere-ocean model.
AB  - A new mercury (Hg) evasion model for the Adriatic Sea was developed accounting
      for the ocean mixed layer depth in order to decrease Hg depletion at the surface.
      Previously modelled airborne Hg species and measured Hg in the ocean were used.
      Simulations were run using one- and two-way coupled atmosphere-ocean models.
      Discrepancies in evasion between the applied coupling schemes were shown to be
      insignificant. The model was evaluated by applying various wind parameterisations
      and diffusive coefficient formulae. Relatively high discrepancies among the
      applied methods were observed. The results of a shorter simulation were
      extrapolated over a one-year period by applying a measurement-based adaptation.
      We obtained good agreement with previously published data on Hg evasion in the
      entire Mediterranean area, thus confirming the suitability of the new model for
      Hg evasion simulations. Model computations performed for the Adriatic Sea
      resulted in levels of evasion approximately two times lower than previously
      estimated.

PMID- 30301016
TI  - Root activities and arsenic translocation of Avicennia marina (Forsk.) Vierh
      seedlings influenced by sulfur and iron amendments.
AB  - Sulfur and iron are abundant and have close, complex interactions with the
      biogeochemical cycle of arsenic (As) in mangrove ecosystems. A hydroponic
      experiment was conducted to investigate the influences of variable SO42- and Fe2+
      supplies on radial oxygen loss (ROL), iron plaque formation and As translocation
      in Avicennia marina upon exposure to As(III). The results indicate that A. marina
      is an As-tolerant plant, the application of iron and sulfur not only showed
      positive growth effects but also induced much higher amounts of ROL-induced iron
      plaque formation on root surfaces. The presence of iron plaque remarkably
      improved the proportion of As sequestration near this area but consequently
      reduced the proportion of As translocation in root. Therefore, it is concluded
      that iron plaque may act as a barrier for protection against As, and iron and
      sulfur play important roles in controlling the growth and translocation of As in
      A. marina seedlings.

PMID- 30301017
TI  - Assessing the impacts of seabed mineral extraction in the deep sea and coastal
      marine environments: Current methods and recommendations for environmental risk
      assessment.
AB  - Mineral extraction from the seabed has experienced a recent surge of interest
      from both the mining industry and marine scientists. While improved methods of
      geological investigation have enabled the mapping of new seafloor mineral
      reserves, the ecological impacts of mining in both the deep sea and the shallow
      seabed are poorly known. This paper presents a synthesis of the empirical
      evidence from experimental seabed mining and parallel industries to infer the
      effects of seabed mineral extraction on marine ecosystems, focusing on
      polymetallic nodules and ferromanganese concretions. We use a problem-structuring
      framework to evaluate causal relationships between pressures caused by nodule
      extraction and the associated changes in marine ecosystems. To ensure that the
      rationale behind impact assessments is clear, we propose that future impact
      assessments use pressure-specific expert elicitation. We further discuss
      integrating ecosystem services in the impact assessments and the implications of
      current methods for environmental risk assessments.

PMID- 30301018
TI  - Study of the oil interaction towards oil spill recovery skimmer material: Effect
      of the oil weathering and emulsification properties.
AB  - The primary aim of this research was to identify the physicochemical properties
      of the oil and water-in-oil (W/O) emulsions used during a NOFO Oil-on-Water field
      trials that reduced the performance of the skimmers recovery efficacy during the
      trials. Extensive studies were performed at SINTEF laboratories with the residues
      of oil topped (i.e. evaporative loss of crude oil components by distillation
      process at large scale) for the field trial and compared it with different
      residues of oil topped by bench scale laboratory procedures. In order to obtain a
      sufficient stable W/O emulsion for the field trial, bunker fuel oil (IFO380) and
      various concentrations of an emulsifier (Paramul(r)) were also added to the
      residues of oil topped on large scale and investigated through interfacial
      tension, contact angle, droplet adhesion and "dip and withdraw" tests. The
      investigations revealed that the addition of an emulsifier lowered the
      interfacial tension of oil residues, which consequently reduced the adherence
      properties of the oil and emulsions to the surface of the skimmer material. Too
      high concentration of an emulsifier (>0,5%) also had a negative effect on the
      stability of W/O emulsion.

PMID- 30301019
TI  - Phycotoxins in scallops (Patinopecten yessoensis) in relation to source,
      composition and temporal variation of phytoplankton and cysts in North Yellow
      Sea, China.
AB  - The North Yellow Sea is a major aquaculture production area for the scallop
      Patinopecten yessoensis. In this study, the temporal and spatial variation of
      phycotoxins in scallops, phytoplankton, and their cysts were analyzed during a
      survey conducted from June 2011 to April 2012 around Zhangzi Island. The study
      area is a semi-enclosed epicontinental sea surrounded by the Shandong Peninsula,
      the Liaodong Peninsula and the Korean Peninsula. The three main results of the
      study were as follows: (1) The saxitoxin-group toxins, okadaic acid and
      analogues, and pectenotoxins were the major phycotoxin residues found in
      scallops; (2) Six kinds of toxic microalgae were identified, Protoperidinium
      spp., Gonyaulax spp., and Alexandrium spp. were the dominant taxa; Seven types of
      potential marine toxin-producing dinoflagellates, A. tamarense, A. catenella,
      Dinophysis fortii, G. catenatum, Gambierdiscus toxicus, Azadinium poporum, and
      Pseudo-nitzschia pungen were identified as the primary source of phycotoxins and
      were present at relatively high density from June to October; and (3)
      azaspiracids and domoic acid might be new potential sources of toxin pollution.
      This study represents the first assessment to phycotoxins around Zhangzi Island
      in the North Yellow Sea.

PMID- 30301020
TI  - Fine sediment and particulate organic matter: A review and case study on ridge-to
      reef transport, transformations, fates, and impacts on marine ecosystems.
AB  - Studies documenting the effects of land-derived suspended particulate matter
      (SPM, i.e., particulate organic matter and mineral sediment) on marine ecosystems
      are typically disconnected from terrestrial studies that determine their origin,
      transport and fate. This study reviews sources, transport, transformations, fate
      and effects of SPM along the 'ridge-to-reef' continuum. We show that some of the
      SPM can be transported over long distances and transformed into large and easily
      resuspendible organic-rich sediment flocs. These flocs may lead to prolonged
      reductions in water clarity, impacting upon coral reef, seagrass and fish
      communities. Using the Great Barrier Reef (NE Australia) as a case study, we
      identify the latest research tools to determine thresholds of SPM exposure,
      allowing for an improved appreciation of marine risk. These tools are used to
      determine ecologically-relevant end-of-basin load targets and reliable marine
      water quality guidelines, thereby enabling enhanced prioritisation and management
      of SPM export from ridge-to-reef.

PMID- 30301021
TI  - Heavy metals, OCPs, PAHs, and PCDD/Fs contamination in surface sediments of a
      coastal lagoon (Valli di Comacchio, NW Adriatic, Italy): Long term trend (2002
      2013) and effect on benthic community.
AB  - Surface sediments contamination (heavy metals, organochlorine pesticides,
      polycyclic aromatic hydrocarbons, polychlorinated dibenzodioxins and
      dibenzofurans) and benthic community of the Valli di Comacchio, were analysed
      from 2002 to 2013. Along the studied period, most of analysed pollutants did not
      exceed thresholds for Good chemical status of sediments. In 2008, a peak of
      contamination was observed, with total PAHs and OCPs exceeding their threshold.
      Considering metals, Ni and Cr exceeded their thresholds, but not the background
      levels for the area, suggesting natural enrichment; conversely Pb exceeded
      background levels for the area in many samples, but it exceeded its sediment
      quality thresholds only in few samples (2006, 2009, 2011). Conversely, the
      ecological status evaluated though AMBI and M-AMBI, was below the Good/Moderated
      thresholds established by WFD in most of the studied years. In the 11 yrs-study
      period, the benthic community showed a very weak response to chemical
      contamination.

PMID- 30301022
TI  - Aggregate dredging impacts in South East England: Improving ecological health by
      integrating fisher ecological knowledge with scientific research.

PMID- 30301023
TI  - Marine conservation in Oceania: Past, present, and future.
AB  - The people of Oceania have long relied on the ocean for sustenance, commerce, and
      cultural identity, which promulgated a sophisticated understanding of the marine
      environment and its conservation. Global declines in ocean health now require
      innovative solutions that can benefit from customary knowledge and practices,
      which in the past led to sustainable marine resource use. The resurgence of local
      stewardship, which incorporates customary practices and governance, has shown
      promise in many locations throughout the Pacific, although a complete return to
      past practices is not fully implementable owing to the loss of traditional
      knowledge, centralized governmental structures, economic development, and
      globalization. Hybrid systems that incorporate elements of customary and
      contemporary management can overcome some of these limitations to implementation
      of successful local management, and lead to greater food security, social
      cohesion, and the creation of an adaptive system that can potentially mitigate
      the effects of climate change and other stressors.

PMID- 30301025
TI  - Entanglement of birds in plastics and other synthetic materials.
AB  - Entanglement of animals is one of the main environmental impacts of waste
      plastic. A 2015 review of entanglement records found that the proportion of
      affected seabirds increased from 16% of species to 25% over the last two decades.
      However, this was restricted to published records; Google Images and other web
      based sources indicate that at least 147 seabird species (36%), as well as 69
      freshwater birds (10%) and 49 landbirds (0.5%) from 53 families have been
      entangled in plastic or other synthetic materials. Fishing gear is responsible
      for entangling most species (83%), although it is often difficult to
      differentiate entanglement from bycatch on active gear. Mitigation measures
      include banning high-risk applications where there are alternatives (e.g. six
      pack rings), discouraging the use of high-risk items (e.g. balloons on strings,
      'manja' kites), and encouraging fishers to not discard waste fishing gear by
      providing specific receptacles and associated educational signage in fishing
      areas.

PMID- 30301024
TI  - Performance characteristics of the temperature-modified ISO 9308-1 method for the
      enumeration of Escherichia coli in marine and inland bathing waters.
AB  - This study defines performance characteristics of the temperature-modified ISO
      9308-1 method for E. coli enumeration in bathing water. After a 4-hour
      resuscitation period at 36 +/- 2  degrees C, the incubation temperature was
      changed to 44 +/- 0.5  degrees C. Elevated incubation temperature significantly
      suppressed the growth of thermo-intolerant bacteria, and enhanced the selectivity
      of Chromogenic Coliform Agar (CCA) up to 49.5% for inland and up to 66.0% for
      coastal water. Consequently, most of the selectivity-related performance
      characteristics are improved. Relative recovery was determined by comparing an
      alternative method against the reference, ISO 9308-1:2014 method, following the
      criteria set out in ISO 17994:2014. Temperature modification did not
      significantly alter the results and the methods were evaluated as "not different"
      for both, coastal and inland waters. Chromogenic Coliform Agar was assessed as a
      suitable medium for reliable E. coli enumeration in bathing water when incubated
      for 17-19 h at 44 +/- 0.5  degrees C after the 4-5 h resuscitation period at 36
      +/- 2  degrees C.

PMID- 30301026
TI  - Variability in sediment-water carbonate chemistry and bivalve abundance after
      bivalve settlement in Long Island Sound, Milford, Connecticut.
AB  - Cues that drive bivalve settlement and abundance in sediments are not well
      understood, but recent reports suggest that sediment carbonate chemistry may
      influence bivalve abundance. In 2013, we conducted field experiments to assess
      the relationship between porewater sediment carbonate chemistry (pH, alkalinity
      (At), dissolved inorganic carbon (DIC)), grain size, and bivalve abundance
      throughout the July-September settlement period at two sites in Long Island Sound
      (LIS), CT. Two dominate bivalves species were present during the study period Mya
      arenaria and Nucula spp. Akaike's linear information criterion models, indicated
      29% of the total community abundance was predicted by grain size, salinity, and
      pH. When using 2 weeks of data during the period of peak bivalve settlement, pH
      and phosphate concentrations accounted 44% of total bivalve community composition
      and 71% of Nucula spp. abundance with pH, phosphate, and silica. These results
      suggest that sediment carbonate chemistry may influence bivalve abundance in LIS.

PMID- 30301027
TI  - Do microplastics affect marine ecosystem productivity?
AB  - Marine and coastal ecosystems are among the largest contributors to the Earth's
      productivity. Experimental studies have shown negative impacts of microplastics
      on individual algae or zooplankton organisms. Consequently, primary and secondary
      productivity may be negatively affected as well. In this study we attempted to
      estimate the impacts on productivity at ecosystem level based on reported
      laboratory findings with a modelling approach, using our biogeochemical model for
      the North Sea (Delft3D-GEM). Although the model predicted that microplastics do
      not affect the total primary or secondary production of the North Sea as a whole,
      the spatial patterns of secondary production were altered, showing local changes
      of +/-10%. However, relevant field data on microplastics are scarce, and strong
      assumptions were required to include the plastic concentrations and their impacts
      under field conditions into the model. These assumptions reveal the main
      knowledge gaps that have to be resolved to improve the first estimate above.

PMID- 30301028
TI  - Historical trends of anthropogenic metals in sediments of Jiaozhou Bay over the
      last century.
AB  - Reconstructing heavy metal historical trends are essential for better
      understanding anthropogenic impact on marine ecosystems. In this work, the
      ecological risk and sources of Cr, Mn, Ni, Cu, Zn, As, Cd, and Pb in Jiaozhou Bay
      were studied and the anthropogenic metal emissions was also quantified. The
      ecological risk was mainly caused by Cd, As and Cu, which presented an increasing
      trend with increased anthropogenic activities since the 1950s. The statistical
      analysis show that Cr, Mn, Ni, Cu and Zn were primarily from natural sources.
      Cadmium and Mn might originate from both natural and anthropogenic sources.
      Arsenic and Pb were sourced from agricultural activities and atmospheric
      precipitation, respectively. The anthropogenic flux of Cr, Mn, Ni, Cu, Zn, As, Cd
      and Pb were 138, 586, 63, 66, 161, 35, 0.31 and 44 mg/m2/a since the 1950s. Over
      40.0% of Cu and As were quantified from anthropogenic emissions since the 1950s.

PMID- 30301029
TI  - Extended-spectrum-beta-lactamase (CTX-M)-producing Escherichia coli in wild
      fishes from a polluted area in the Atlantic Coast of South America.
AB  - The presence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia
      coli in oceanic ecosystems constitutes an emerging public health risks in the
      marine environment. In this study, we report for the first time the
      identification of ESBL (CTX-M)-producing E. coli in wild fishes from a polluted
      area in the South Atlantic coast of Brazil, where a genomic analysis confirm the
      presence of livestock and human E. coli lineages belonging to sequence types
      (STs) ST744 and ST746, which carried clinically relevant resistance genes for
      human and veterinary antibiotics, and heavy metals. These findings reveal the
      presence of multidrug-resistant (MDR) bacteria in the gut microbiota of wild
      fishes living in polluted coastal waters, alerting that microbial contamination
      by bacteria related directly and indirectly to human or animal activities could
      affect the safety of the seafood supply, as well as the commercial and
      recreational use of coastal marine waters.

PMID- 30301030
TI  - Influence of thermooxidative degradation on the in situ fate of polyethylene in
      temperate coastal waters.
AB  - Polyethylene is a commonly used polymer in plastic products and is often found as
      marine litter. Nevertheless there is limited knowledge about what happens to the
      material when it ends up in the sea. Polyethylene films were therefore thermally
      oxidised to four different levels of degradation. The films were then placed in
      stainless-steel cages in the sea off the Swedish west coast for 12 summer weeks.
      Subsamples were analysed with respect to biofouling, degradation and buoyancy.
      All levels showed a continued oxidation in the field. The pre-degraded films
      started fragmenting and the non-degraded films showed a decrease in tensile
      strain. All levels showed increased biofouling with higher presence of
      filamentous algae and bryozoans on pre-degraded materials. The density (kg.m-3)
      of the films was seen to increase slightly, and the apparent density for the pre
      degraded films (density of the films with biofilm) showed a strong increase,
      which resulted in sinking.

PMID- 30301031
TI  - Underwater noise levels of pile-driving in a New Zealand harbour, and the
      potential impacts on endangered Hector's dolphins.
AB  - Impact pile-driving generates loud underwater anthropogenic sounds, and is
      routinely conducted in harbours around the world. Surprisingly few studies of
      these sounds and their propagation are published in the primary literature. To
      partially redress this we studied pile-driving sounds in Lyttelton Harbour, New
      Zealand, during wharf reconstruction after earthquake damage. That Lyttelton
      harbour is routinely used by Hector's dolphins (Cephalorhynchus hectori), an
      endangered species found only in New Zealand, provided further context for this
      study. Steel piles of 0.61 or 0.71 m diameter were driven using three different
      pile-drivers. Maximum calculated source SEL was 192 dB re 1 MUPa2s @ 1 m (SPL0-p
      of 213 dB re 1 MUPa @ 1 m). Propagation of piling noise was strongly influenced
      by harbour bathymetry and a rock breakwater near the piling operation. We
      calculated range estimates at which Hector's dolphins may suffer temporary
      hearing threshold shift and behavioural change.

PMID- 30301032
TI  - Hydrocarbon-degradation and MOS-formation capabilities of the dominant bacteria
      enriched in sea surface oil slicks during the Deepwater Horizon oil spill.
AB  - A distinctive feature of the Deepwater Horizon (DwH) oil spill was the formation
      of significant quantities of marine oil snow (MOS), for which the mechanism(s)
      underlying its formation remain unresolved. Here, we show that Alteromonas strain
      TK-46(2), Pseudoalteromonas strain TK-105 and Cycloclasticus TK-8 - organisms
      that became enriched in sea surface oil slicks during the spill - contributed to
      the formation of MOS and/or dispersion of the oil. In roller-bottle incubations,
      Alteromonas cells and their produced EPS yielded MOS, whereas Pseudoalteromonas
      and Cycloclasticus did not. Interestingly, the Cycloclasticus strain was able to
      degrade n-alkanes concomitantly with aromatics within the complex oil mixture,
      which is atypical for members of this genus. Our findings, for the first time,
      provide direct evidence on the hydrocarbon-degrading capabilities for these
      bacteria enriched during the DwH spill, and that bacterial cells of certain
      species and their produced EPS played a direct role in MOS formation.

PMID- 30301033
TI  - Experimental and modeled thermoregulatory costs of repeated sublethal oil
      exposure in the Double-crested Cormorant, Phalacrocorax auritus.
AB  - To fully understand the impact of oil exposure, it is important to understand
      sublethal effects like how increased thermoregulatory costs may affect survival
      and reproduction. However, it is difficult and time-consuming to measure these
      effects in wild animals. We present a novel use of a bioenergetics model, Niche
      MapperTM, to estimate thermoregulatory impacts of oiling, using data from captive
      Double-crested Cormorants (Phalacrocorax auritus) experimentally exposed to oil.
      Oiled cormorants had significant increases in surface body temperatures following
      exposure. Niche Mapper accurately predicted surface temperatures and metabolic
      rates for unoiled and oiled cormorants and predicted 13-18% increased daily
      energetic demands due to increased thermoregulatory costs of oiling, consistent
      with increased food consumption observed in experimentally oiled cormorants. We
      show that Niche Mapper can provide valuable insight into sublethal oiling effects
      by quantifying the extent to which thermoregulatory costs divert energy resources
      away from important life processes like maintenance, reproduction and migration.

PMID- 30301034
TI  - Spreading of drill cuttings and sediment recovery of three exploration wells of
      different ages, SW Barents Sea, Norway.
AB  - Five stations (<=250 m from the well heads) from three exploration wells of
      different ages from the SW Barents Sea were studied to investigate the spreading
      of drill cuttings and sediment quality. Two of the wells were drilled before the
      restriction of use of oil-based drilling fluids (1993). Elevated concentrations
      of Ba were found in sediments near all the wells with the highest concentrations
      at <=60 m from the well head. The thickness of drill cutting layers was between
      >20 cm (well head) and 2 cm (250 m from the well head). The sediment quality
      varied from very bad (oldest well) to background (normal) (newer wells).
      Regulations led to better sediment quality. Metal concentrations from the oldest
      well suggested that the top 4 cm of the core represents sediment recovery.
      However, Ba concentrations of the top sediment layer at all the stations of the
      three wells indicate no physical recovery.

PMID- 30301035
TI  - Effects of increasing nutrient disturbances on phytoplankton community structure
      and biodiversity in two tropical seas.
AB  - Statistical analysis of rainfall data from 2005 to 2015 showed that atmospheric
      deposition supplied large amount of dissolved inorganic nitrogen (38-155 mg.m
      2.month-1) in N-deficient South China Sea and Eastern Indian Ocean. To understand
      marine ecosystem responses to increasing nutrient disturbances, we implemented
      field mesocosm experiments to study phytoplankton community structure and
      biodiversity responses to nutrient treatments with nitrate, phosphate and iron
      across tropical seas. Our results showed that DIN supply would change
      phytoplankton community structure and stimulated the regime shift from
      cyanobacteria to diatoms (relative dominance R > 0). Phytoplankton communities
      were dominated by diatoms (relative abundance >50%) accompanied by high
      chlorophyll a content with 1.58-39.27 MUg.L-1 in DIN-added cultures, whereas
      cyanobacteria dominated communities (relative abundance >60%) with low biomass of
      0.12-0.18 MUg.L-1 in undisturbed cultures. Simultaneously increased DIN loading
      from atmospheric deposition would decrease ecological diversity of tropical seas
      owing to species competition and succession (Shannon diversity H' decreased to
      <1).

PMID- 30301036
TI  - Mobility versus retention of mercury in bare and salt marsh sediments of a
      recovering coastal lagoon (Ria de Aveiro, Portugal).
AB  - During decades, mercury (Hg) was discharged into the Aveiro Lagoon. Twenty-five
      years after the cessation of discharges, sediment cores were collected at two
      areas to assess the evolution of the mercury contamination status. Vertical Hg
      profiles differed considerably between bare and vegetated sediments. Bare
      sediments contained significantly less Hg (<8 mg kg-1) than historical data of
      1995 (up to 40 mg kg-1), probably resulting from erosion. Salt marsh sediments
      were marked by a Hg sub-surface enrichment, reaching 44 mg kg-1 in the site
      closer to the industrial discharge point. High Hg concentrations in 2007, 2011
      and 2016 were found at similar sediment layers. These results emphasise the role
      of halophyte plants in the cycling and retention of Hg in sediments. The
      persistency of high Hg in the upper marsh layers highlights the complexity in the
      recovery of historically contaminated marshes and the vulnerability to
      modifications in hydrology associated with climate changes.

PMID- 30301037
TI  - Suspended microplastics in a highly polluted bay: Abundance, size, and
      availability for mesozooplankton.
AB  - Microplastic ingestion by mesozooplankton may be an important pathway for the
      microplastics to enter the food web. To determine microplastic abundance in
      Guanabara Bay, samples were collected by neustonic haul with a 64-MUm-net and
      oblique hauls using 64- and 200-MUm nets. Microplastic size and abundance as well
      as copepod, fish-larvae, and chaetognath sizes, densities, and preferential prey
      sizes were determined. Microplastic abundance was higher in samples collected
      with fine nets (average 4.8 microplastics m-3, maximum 11 microplastics m-3) than
      in those collected with coarse net. Microplastic abundance in Guanabara Bay was
      higher than that in other marine ecosystems. Microplastics >100 MUm were too
      large to be ingested by copepods. However, for fish larvae and chaetognaths, the
      abundance of microplastics, at the corresponding prey size range, were,
      respectively, ~9000- and 14,400-folds lower than the preferential copepod prey,
      in the same size range. Thus, in Guanabara Bay, microplastics were available, but
      too diluted to be frequently ingested by fish larvae and chaetognaths.

PMID- 30301038
TI  - Testing performances of marine benthic biotic indices under the strong
      seasonality in the tropical intertidal habitats, South Andaman, India.
AB  - Understanding the natural variability and its influence on the performance of
      marine biotic indices used for the health assessment of marine ecosystem is the
      prime concern. This study addresses the seasonal variability of univariate and
      multimetric indices by using macrobenthic data collected from three intertidal
      habitats for two years (July 2013-July 2015). The univariate indices viz.,
      abundance, richness, Shannon index and ES (100) showed strong seasonal
      variability. For the multimetric indices, the seasonal variability was low and
      appeared site specific. W-statistics, AMBI and M-AMBI showed highest constancy
      whilst BENTIX and BOPA exhibited wide - ranging. A general tendency could be
      inferred as majority of indices showed improvement in benthic quality (poor -
      moderate and good - high) from turbulent monsoon to stable dry period. The
      results are discussed concerning possible consequences especially related to the
      benthic community and biotic indices in intertidal habitats under the influence
      of sewage discharge and monsoonal effects.

PMID- 30301039
TI  - First report of occurrence, distribution, and composition of microplastics in
      surface waters of the Sea of Marmara, Turkey.
AB  - Plastic is produced today in large quantities and used for many purposes. At the
      end of use, a large part of it gets into the environment, often into the sea and
      there it is fragmented into the smallest fragments, so-called microplastic (MP).
      MPs pose a serious challenge to the marine environment such as the sources and
      properties of MP particles, their impact on marine organisms, and the challenges
      of environmental pollution. This work, carried out in the fourteen sites in the
      area, is the first reference to the detection of MP distribution at surface
      waters in the Sea of Marmara, Turkey. As a result of this study, the average
      level of MP in the surface was determined to be 1.263 item/m2. The results were
      higher compared of the most other adjacent regions and show that the Sea of
      Marmara started to face that problem.

PMID- 30301040
TI  - Assessing vessel slowdown for reducing auditory masking for marine mammals and
      fish of the western Canadian Arctic.
AB  - Vessel slowdown may be an alternative mitigation option in regions where re
      routing shipping corridors to avoid important marine mammal habitat is not
      possible. We investigated the potential relief in masking in marine mammals and
      fish from a 10 knot speed reduction of container and cruise ships. The mitigation
      effect from slower vessels was not equal between ambient sound conditions,
      species or vessel-type. Under quiet ambient conditions, a speed reduction from 25
      to 15 knots resulted in smaller listening space reductions by 16-23%, 10-18%, 1
      2%, 5-8% and 8% respectively for belugas, bowheads, bearded seals, ringed seals,
      and fish, depending on vessel-type. However, under noisy conditions, those
      savings were between 9 and 19% more, depending on the species. This was due to
      the differences in species' hearing sensitivities and the low ambient sound
      levels measured in the study region. Vessel slowdown could be an effective
      mitigation strategy for reducing masking.

PMID- 30301041
TI  - Microplastics in mussels and fish from the Northern Ionian Sea.
AB  - Microplastic ingestion by marine organisms presents an emerging threat to marine
      ecosystems; microplastics in different marine species are currently reported
      worldwide. This study aims to assess microplastic ingestion in four, highly
      commercial, marine species from Greek waters in the Northern Ionian Sea
      (Mediterranean Sea). Microplastics were found in mussels (Mytilus
      galloprovincialis) and all three fish species (Sardina pilchardus, Pagellus
      erythrinus, Mullus barbatus) examined. The frequency of occurrence of ingested
      microplastics was 46.25% in mussels, while among fish species, S. pilchardus
      showed the highest frequency of microplastic ingestion (47.2%). Microplastic
      abundance ranged from 1.7-2 items/individual in mussels and from 1.5-1.9
      items/individual in fish. The majority of ingested microplastics were fragments,
      while their color and size varied. Fourier Transform Infrared Spectroscopy (FT
      IR) indicated polyethylene as the most common polymer type in mussels and fish.
      Results can be used to set baseline levels for the assessment of microplastic
      pollution in the Ionian Sea.

PMID- 30301042
TI  - First data on plastic ingestion by blue sharks (Prionace glauca) from the
      Ligurian Sea (North-Western Mediterranean Sea).
AB  - Few studies have focused so far on plastic ingestion by sharks in the
      Mediterranean Sea. The aim of this paper was to determine, for the first time,
      the plastic litter ingested by blue sharks (Prionace glauca), categorized as
      "Critically Endangered" in the Mediterranean Sea by IUCN, caught in the Pelagos
      Sanctuary SPAMI (North-Western Mediterranean Sea). The analysis of the stomach
      contents was performed following the MSFD Descriptor 10 standard protocol
      implemented with FT-IR spectroscopy technique. The results showed that 25.26% of
      sharks ingested plastic debris of wide scale of sizes from microplastics (<5 mm)
      to macroplastics (>25 mm). The polyethylene sheetlike user plastics, widely used
      as packaging material, are the most ingested debris. This research raises a
      warning alarm on the impact of plastic debris on a threatened species, with a key
      role in the food web, and adds important information for futures mitigation
      actions.

PMID- 30301044
TI  - Intensive anthropogenic activities had affected Daya Bay in South China Sea since
      the 1980s: Evidence from heavy metal contaminations.
AB  - Sediment geochemical characteristics were analyzed to assess how anthropogenic
      activities affected the Daya Bay, a subtropics bay adjacent to the most
      economically developed region of China. Vertical profiles of heavy metal contents
      and their enrichment factors indicated the development of Daya Bay environment in
      the past 100 years basically experienced three stages, which were closely
      consistent with the economic development. Before 1980s, the concentration of
      heavy metals was basically at the background level. Contamination of metals,
      particularly for Cr, Ni, Cu, Zn, Cd, and Pb, generally began in mid-1980s and
      became serious in 2000s. However, after late-2000s, the sediment quality had been
      radically improved. Heavy metals in nearshore sediment of Daya Bay were all
      closely related with import of anthropogenic and/or terrestrial material, whereas
      those in offshore were likely to be related with joint influence from the
      anthropogenic activities and the natural processes.

PMID- 30301043
TI  - Proteome responses of Gracilaria lemaneiformis exposed to lead stress.
AB  - Proteome response of plants is an important process that enables them to cope
      with environmental stress including metal stress. In this study, the proteome of
      Gracilaria lemaneiformis exposed to lead was investigated. Two-dimensional gel
      electrophoresis analysis revealed 123 protein spots, among which 14 proteins were
      significantly differentially expressed and identified using MALDI-TOF MS. Two of
      the up-regulated proteins were identified and predicted to be involved in
      photosynthesis and signal transduction, while eleven down-regulated proteins were
      functionally grouped into five classes including photosynthesis, energy
      metabolism, protein metabolism, carbohydrate transport and metabolism, and
      antioxidation proteins. There was also an up-regulation in superoxide dismutase,
      peroxidase, glutathione s-transferase, and heat-shock protein 70 upon Pb
      exposure. Proteomic studies provide a better picture of protein networks and
      metabolic pathways primarily involved in intracellular detoxification and defense
      mechanisms.

PMID- 30301045
TI  - Contributions of pre- versus post-settlement processes to fluctuating abundance
      of crown-of-thorns starfishes (Acanthaster spp.).
AB  - Numerous hypotheses have been put forward to account for population outbreaks of
      crown-of-thorns starfishes (CoTS, Acanthaster spp.), which place specific
      importance on either pre- or post-settlement mechanisms. The purpose of this
      review is to specifically assess the contributions of pre- versus post-settlement
      processes in the population dynamics of CoTS. Given the immense reproductive
      potential of CoTS (>100 million eggs per female), persistent high densities would
      appear inevitable unless there were significant constraints on larval
      development, settlement success, and/or early post-settlement growth and
      survival. In terms of population constraints, pre- and post-settlement processes
      are both important and have additive effects to suppress densities of juvenile
      and adult CoTS within reef ecosystems. It is difficult, however, to assess the
      relative contributions of pre- versus post-settlement processes to population
      outbreaks, especially given limited data on settlement rates, as well as early
      post-settlement growth and mortality. Prioritising this research is important to
      resolve potential effects of anthropogenic activities (e.g., fishing) and habitat
      degradation on changing population dynamics of CoTS, and will also improve
      management effectiveness.

PMID- 30301046
TI  - A critical review of marine snow in the context of oil spills and oil spill
      dispersant treatment with focus on the Deepwater Horizon oil spill.
AB  - Natural marine snow (NMS) is defined as the "shower" of particle aggregates
      formed by processes that occur in the world's oceans, consisting of macroscopic
      aggregates of detritus, living organisms and inorganic matter. Recent studies
      from the Deepwater Horizon oil spill suggest that marine snow is also formed in
      association with oil spills and was an important factor for the transport of oil
      to the seabed. This review summarizes the research and literature on MS, mainly
      from the DWH oil spill, with a focus on the relation between the use of oil spill
      dispersants and the formation and fate of oil-related marine snow (ORMS). Studies
      are still required to determine ORMS processes at oil concentrations as relevant
      as possible for chemically dispersed oil.

PMID- 30301047
TI  - Sustainable recycling of mooring ropes from decommissioned offshore platforms.
AB  - Decommissioning offshore Floating Production, Storage and Offloading (FPSO)
      platforms requires extensive technical knowledge, since it generates different
      post-consumer materials, including mooring lines. These ropes are made from
      polyester high tenacity yarn, based on polyethylene terephthalate (PET), and
      their high added value means they should not be discarded as scrap. This paper
      aims to present a review and technical opportunities, from an economic
      standpoint, of recycling the mooring lines recovered from decommissioned FPSOs.
      Studies conducted over the last two years have researched and developed different
      potential applications for the fibers. These studies include collaborative
      project initiatives involving technical and management professionals,
      universities and private enterprises, with a view to achieving a more sustainable
      destination for these fibers.

PMID- 30301048
TI  - 20th century increase in body size of a hypoxia-tolerant bivalve documented by
      sediment cores from the northern Adriatic Sea (Gulf of Trieste).
AB  - An increase in the frequency of hypoxia, mucilages, and sediment pollution
      occurred in the 20th century in the Adriatic Sea. To assess the effects of these
      impacts on bivalves, we evaluate temporal changes in size structure of the
      opportunistic bivalve Corbula gibba in four sediment cores that cover the past
      ~500 years in the northern, eutrophic part and ~10,000 years in the southern,
      mesotrophic part of the Gulf of Trieste. Assemblages exhibit a stable size
      structure during the highstand phase but shift to bimodal distributions and show
      a significant increase in the 95th percentile size during the 20th century. This
      increase in size by 2-3 mm is larger than the northward size increase associated
      with the transition from mesotrophic to eutrophic habitats. It coincides with
      increasing concentrations of total organic carbon and nitrogen, and can be
      related to enhanced food supply and by the tolerance of C. gibba to hypoxia.

PMID- 30301049
TI  - Plastic litter transfer from sediments towards marine trophic webs: A case study
      on holothurians.
AB  - This study estimates for the very first time plastic litter levels in sea
      cucumbers (Echinodermata, Holothuroidea) sampled in situ and their intakes from
      sediments in three different rocky bottom habitats (slides, cliff, banks) settled
      in Salina Island (Aeolian Archipelago). Macroplastic were never recorded while
      meso- and microplastics were identified in all sediment (81-438 items/kg d.w.)
      and animal samples (1.8-22 items/ind.). Plastic intakes by sea cucumbers resulted
      frequently associated to the size range included within 100-2000 MUm. Over than
      70% of ingested plastic litter is represented by the size fraction >500 MUm.
      Sediment/animals ratios % are included 2.7 +/- 2.0% in studied habitats with a
      selective intake of fragments occurring in slides. Furthermore, results support
      the occurrence of selective ingestion of plastic litter by holothurians in
      natural environments underlining the role of these species in microplastic
      transfer from abiotic towards biotic compartments of the marine trophic web.

PMID- 30301050
TI  - Using a genetic algorithm to improve oil spill prediction.
AB  - The performance of oil spill models is strongly influenced by multiple
      parameters. In this study, we explored the ability of a genetic algorithm (GA) to
      determine optimal parameters without the need for time-consuming manual attempts.
      An evaluation function integrating the percentage of coincidence between the
      predicted polluted area and the observed spill area was proposed for measuring
      the performance of a Lagrangian oil particle model. To maximise the objective
      function, the oil spill was run numerous times with continuously optimised
      parameters. After many generations, the GA effectively reduced discrepancies
      between model results and observations of a real oil spill. Subsequent validation
      indicated that the oil spill model predicted oil slick patterns with reasonable
      accuracy when equipped with optimal parameters. Furthermore, multiple objective
      optimisation for observations at different times contributed to better model
      performance.

PMID- 30301051
TI  - Development of analytical methods used for the study of 2,4,6-trinitrotoluene
      degradation kinetics in simulated sediment samples from the Baltic Sea.
AB  - Large amounts of ammunition containing 2,4,6-trinitrotoluene (TNT) and other
      substances were dumped in the Baltic Sea after WWII. Considering progressive
      corrosion processes, studying the transformation of TNT occurring in the
      environment constitutes an important aspect of a possible associated risk. This
      study focused on the transformations of TNT in simulated conditions of the Baltic
      Sea bottom sediment. Methods of analysis of TNT and selected products of its
      transformations were developed for that purpose. The developed methods allowed
      for the determination of selected compounds below 1 ng/g. Systematic monitoring
      of TNT transformations in the environment of the bottom sediment was performed.
      This allowed for the determination of the kinetics of TNT degradation and
      identification of degradation reaction products. Based on the obtained results,
      the TNT decay half-time in conditions present in the Baltic Sea was estimated to
      be 16.7 years for the abiotic environment and 5.6 for the biotic environment.

PMID- 30301052
TI  - Microtidal estuaries warrant special management measures that recognise their
      critical vulnerability to pollution and climate change.
AB  - Not all estuaries are equally susceptible to anthropogenic perturbation.
      Microtidal estuaries with long residence times are intrinsically less robust than
      well-flushed macrotidal estuaries, facilitating the accumulation of contaminants.
      This promotes development of blooms of non-toxic and toxic phytoplankton, and
      hypoxia and anoxia may occur in deeper sections of the typically stratified water
      column. In Mediterranean and arid climates, high temperatures and low and/or
      seasonal rainfall can result in marked hypersalinity. Thus, any increase in
      anthropogenic perturbation will further decrease the health of a system in which
      the biota already experiences natural stress. Microtidal estuaries are also more
      susceptible to climate change, the detrimental longer-term effects of which are
      becoming manifestly obvious. Numerous attempts have been made to develop novel
      solutions to problems caused by eutrophication, phytoplankton blooms, hypoxia and
      hypersalinity, which have met with various levels of success, but the need for
      such measures and effective legislation is increasingly critical.

PMID- 30301053
TI  - Towards cleaner shores: Assessing the Great Canadian Shoreline Cleanup's most
      recent data on volunteer engagement and litter removal along the coast of British
      Columbia, Canada.
AB  - This paper analyzes voluntary cleanups organized by the Great Canadian Shoreline
      Cleanup (GCSC) along the coast of British Columbia (2013-2016). Cleanup
      performance indicators, litter composition and diversity were compared between
      years and across areas (i.e., North Coast of British Columbia, Inner Coast of
      Vancouver Island, West Coast of Vancouver Island, and Southern Strait of
      Georgia). Significant differences in parameters were found between areas but not
      across time. Spatial variation in trash composition and diversity was mostly
      related to source of litter. Trash yield per kilometre of shoreline was higher in
      isolated areas and in areas with exposed shorelines. The majority of recovered
      litter items were composed of plastic. Local actions, complementary to the GCSC,
      such as banning single-use, non-biodegradable takeout containers on beaches,
      implementing trash buyback programs, and modifying waste management and recycling
      regulations, are proposed as mechanisms for strengthening the prevention and
      mitigation of coastal pollution in British Columbia.

PMID- 30301054
TI  - An alternative approach to bioaccumulation assessment of methyl-Hg, total-Hg, Cd,
      Pb, Zn in bivalve Anomalocardia brasiliana from Rio de Janeiro bays.
AB  - We present an alternative approach for establishing in situ bioaccumulation
      assessment of methyl-Hg (MeHg), total-Hg, Cd, Pb and Zn in bivalve Anomalocardia
      brasiliana from four bays of Rio de Janeiro presenting varying degrees of
      eutrophication, acid volatile sulfides (2-55 MUmol g-1), simultaneously extracted
      metals (SEM) and total metals (TM) in sediments. Using metal concentrations of
      composite samples from three size classes of bivalve and their incorporation
      rates (IR = metal concentration / total length), which depend on exposure time,
      we calculated asymptotic IR and respective consequent metal concentrations. Both
      IR and the metal concentration presented inverse relationships with total length
      (excepting MeHg) and bay contamination. Lead and zinc concentrations were above
      Brazilian legal criteria in the most anoxic and contaminated bay, suggesting
      significant metal bioavailability (SEM/TM between 8% and 63%).

PMID- 30301055
TI  - Degradation of petroleum hydrocarbons in seawater by simulated surface-level
      atmospheric ozone: Reaction kinetics and effect of oil dispersant.
AB  - Oil degradation by surface-level atmospheric ozone has been largely ignored in
      the field. To address this knowledge gap, this study investigated the ozonation
      rate and extent of typical petroleum compounds by simulated surface-level ozone,
      including total petroleum hydrocarbons (TPHs), n-alkanes, and polycyclic aromatic
      hydrocarbons (PAHs). Moreover, the work explored the effect of a prototype oil
      dispersant, Corexit EC9500A, on the ozonation rate. Rapid oxidation of TPHs, n
      alkanes and PAHs was observed at various gaseous ozone concentrations (i.e. 86,
      200 and 300 ppbv). Generally, the presence of the oil dispersant enhanced
      ozonation of the oil compounds. The addition of humic acid inhibited the
      reaction, while increasing salinity accelerated the degradation. Both direct
      ozonation by molecular ozone and indirect oxidation by ozone-induced radicals
      play important roles in the degradation process. The findings indicate that
      ozonation should be taken into account in assessing environmental fate and
      weathering of spilled oil.

PMID- 30301056
TI  - Determination of radiological hazard parameters in sea snails (Rapana venosa) in
      the East Black Sea Coast of Turkey.
AB  - The aim of this study was to determine the activity concentrations and
      radiological hazard parameters of 137Cs and 40K in soft tissue samples of sea
      snails (Rapana venosa) collected from 12 different stations in the East Black Sea
      coastal area of Turkey. The values in soft tissues of sea snail samples with
      three different sizes were between 0.31 and 1.79 Bq kg-1 for 137Cs and 163.9 and
      269.4 Bq kg-1 for 40K. The mean activity concentrations of 137Cs and 40K in
      tissues of small-sized sea snails were determined to be higher than those of
      137Cs and 40K in soft tissues of the other sizes. The determined activity
      concentration values were lower than the concentrations reported in similar
      studies. Radiological hazard parameters such as the daily intake (Dint) of 137Cs
      and 40K, annual committed effective dose (Eeff), and lifetime cancer risk (LCR)
      were calculated and compared with the international recommended values.

PMID- 30301057
TI  - Natural radioactivity in the beach sand and soil along the coastline of Guangxi
      Province, China.
AB  - Natural radioactivity in the beach sand and soil was measured and evaluated in
      typical ecosystems of mangroves, seagrasses, and coral reefs along the coastline
      of Guangxi Province, China. Radioactivity in the soil was about three times
      higher than that in the beach sand probably due to the distinct mineral
      components and particle sizes. A comparison with natural radioactivity levels in
      the global beach sands indicated that the beach sand of Guangxi had the lowest
      radioactivity. Radiological parameters including radium equivalent activity
      (Raeq), external and internal hazard indices (Hex and Hin), representative gamma
      level index (Igammar), absorbed gamma dose rate (DR), and annual effective dose
      equivalent (AEDE) were lower than the recommended values. Our results provide
      baseline data on radioactivity in the beach sand and soil along the coastline of
      Guangxi and contribute to the database of radioactivity in the global beach sand.

PMID- 30301058
TI  - Microplastics analysis in Malaysian marine waters: A field study of Kuala Nerus
      and Kuantan.
AB  - The first report on the emergence of microplastic in Malaysian marine waters was
      documented in this study. Water samples were collected from two regions, namely
      Kuala Nerus and Kuantan port, as the representatives of different anthropogenic
      activities. Identification of microplastic was performed based on physical
      characteristics (colour, shape, density) and chemical characterisation (ATR-FTIR
      analysis) for a functional group of polymers. Fragment type, black or grey colour
      and high density (>1.02 g cm-3) of microplastic were the most prevalent
      characteristics found in both areas. Two principal components (density and
      colour) rendered explained about 95.3% (Kuantan) and 95.6% (Kuala Nerus) of the
      total variance. Six possible polymer materials were identified, namely polyester,
      polystyrene, polyamide, polyvinyl chloride, polypropylene, and polyethylene. The
      findings of the study provided good baseline information on marine debris issue
      in Malaysia.

PMID- 30301059
TI  - Using citizen science data to assess the difference in marine debris loads on
      reefs in Queensland, Australia.
AB  - The prevalence of marine debris in global oceans is negatively impacting the
      marine environment. In Australia, marine debris has been an increasing concern
      for sensitive marine environments, such as coral reefs. Citizen science can
      contribute data to explore patterns of subtidal marine debris loads. This study
      uses data from Reef Check Australia to describe patterns of debris abundance on
      reef tourism sites in two Queensland regions, the Great Barrier Reef (GBR) and
      Southeast Queensland (SEQ). Debris was categorized into three groups, fishing
      line, fishing net, and general rubbish. Overall, debris abundance across reefs
      was relatively low (average 0.5-3.3 items per survey (400 m2)), but not absent on
      remote reefs surveyed in the GBR region. Highest debris loads were recorded in
      SEQ near cities and high use areas. These results indicate the presence of marine
      debris on remote and urban reefs, and the applicability of using citizen science
      to monitor debris abundance.

PMID- 30301060
TI  - Photoacclimation to light-limitation in a clionaid sponge; implications for
      understanding sponge bioerosion on turbid reefs.
AB  - Watershed-based pollution is a common form of coral reef degradation. Affected
      reefs are often highly turbid, where light-limitation confines the distribution
      of photosynthetic benthic taxa and the capacity for photoacclimation is important
      for survival. We investigated low light photoacclimation in a Symbiodinium
      hosting bioeroding sponge using in situ PAM fluorometry. Cliona aff. viridis was
      artificially shaded (70 & 95% ambient light reduction) on a low turbidity
      Indonesian reef for 25 days, with a subsequent 14-day recovery period.
      Significant changes in rETRmax, and qP, and a non-significant but observable
      decline in Ek, demonstrated that C. aff. viridis is able to photoacclimate to
      conditions of extreme light reduction and recover within a relatively short
      period of time. The sponge is therefore unlikely to be light limited on even the
      most turbid reefs. However, other aspects of watershed-pollution such as
      sedimentation may still limit their distribution in affected coastal waters.

PMID- 30301061
TI  - An 87-year sedimentary record of mercury contamination in the Old Yellow River
      Estuary of China.
AB  - A sediment core, spanning from the year 1925 +/- 3.03 to 2012, was collected for
      analyzing historical distribution of mercury (Hg) in the Old Yellow River Estuary
      (OYRE), China. The Hg concentrations in the sediment core ranged from 14 to 351
      ng g-1, with the high values occurred in the middle layers (1960-1996), which may
      be resulted from intensive human activities during this period, such as oil
      exploitation and booming of petrochemical industry, salt chemical industry and
      chlor-alkali plants. A significant positive correlation was found between THg and
      loss on ignition (LOI). The main fraction of Hg existed in residual part while
      the fraction that was easy to leach out from sediments accounted for only a small
      portion according to the results of BCR sequential extraction procedure. Multiple
      ecological risks indices and guidelines of Hg indicated that the sedimentary
      record presented an "intermediate state" for Hg contamination in the OYRE.

PMID- 30301063
TI  - Quantification of microfibre levels in South Africa's beach sediments, and
      evaluation of spatial and temporal variability from 2016 to 2017.
AB  - The microfibre content of beach sediment samples was established at 175 sampling
      sites along over 2700 km of South Africa's coastline in 2016 and again in 2017.
      The average microfibre content was 80 +/- 102 F/dm3 in Feb/March 2017 (n = 161),
      and 87 +/- 84 F/dm3 in May/June 2016 (n = 128). These average values, and the
      observed ranges of 0 to 797 F/dm3 in 2017 and 4 to 772 F/dm3 in 2016, are
      consistent with global observations. The highest microfibre levels were observed
      at sampling sites close to large coastal waste water treatment work discharge
      points. Several instances of temporal variability are observed, only some of
      which can be associated with seasonal changes in river runoff. This baseline data
      set is a valuable reference point for identification of priority study sites for
      more detailed study of marine ecosystem response to microfibre pollution.

PMID- 30301062
TI  - Microbial water quality and the detection of multidrug resistant E. coli and
      antibiotic resistance genes in aquaculture sites of Singapore.
AB  - Poor microbial water quality jeopardizes the health and safety of food produced
      by aquaculture farms. Three fish farms and transect sites in Singapore were
      assessed for microbial water quality and antimicrobial resistance determinants.
      Of the 33 multidrug resistant E. coli isolated from surface waters of the Johor
      Straits, 81.8% were ESBL producers. The relative abundance of sul1, qnrA and
      intI1 genes were higher in sediments than surface waters. Among the surface water
      samples, higher concentrations (10-1-101) of beta-lactamases (blaSHV, blaOXA,
      blaCTX-M) were detected in the transect sites. This study highlights a potential
      antimicrobial resistance transmission chain from environmental waters, to animal
      carriers and humans.

PMID- 30301064
TI  - An environmental risk assessment of three organic UV-filters at Lac Bay, Bonaire,
      Southern Caribbean.
AB  - Although organic UV filters (OUVFs) benefit human health by preventing skin burns
      and cancer, several studies revealed that organic UV filters can induce
      developmental and reproductive toxicity to aquatic organisms. Discharge of OUVFs
      occurs predominantly at marine recreational hotspots, such as Lac Bay, Bonaire,
      and is predicted to increase significantly due to growing tourism worldwide.
      Unfortunately, there is no insight what the current and future discharge of OUVF
      at Lac Bay is. Therefore, this study aimed to 1) measure concentrations and
      estimate the risk of specific OUVFs to different nursery habitats at Lac Bay, and
      2) compare measured and predicted concentration based risk assessment outcome.
      Results showed that at least one of the three nurseries at Lac Bay had a
      potential for adverse effects. Furthermore, predicted environmental
      concentrations of UV filter discharge can be applied to gain more insight in the
      order of extent of OUVF discharge by marine tourism.

PMID- 30301065
TI  - Impact of anthropogenic activities on mussel (Mytella guyanensis) in the Gulf of
      Paria, Trinidad.
AB  - This body of work demonstrated the levels of selected contaminants (as well as
      their potential sources), in mussels (Mytella guyanensis) - a known bio-indicator
      of pollution, along the west coast (Gulf-of-Paria) of Trinidad. The findings
      demonstrated that polyaromatic hydrocarbons levels in the mussels investigated
      were moderate to high (201.80-1200.08 MUg/kg). Notably, benzo(a)pyrene levels
      (1.15-9.32 MUg/kg) exceeded the European Union guidelines at various sites. The
      distribution of PAHs and trace elements in the Gulf of Paria are impacted by
      tidal currents and local source discharge. Significant risks were identified from
      toxic carcinogenic equivalent levels (3.01 to 22.37 MUg/kg) and mutagenic
      equivalent levels (3.98 to 38.61 MUg/kg). The concentration of trace elements, Zn
      (46.05-56.36 mg/kg) and Cd (0.46-1.17 mg/kg), exceeded both local and
      international guidelines at certain sites investigated. The analysis revealed a
      high bioavailability of the identified pollutants in the Gulf of Paria from
      industrial, urban and marine activities.

PMID- 30301066
TI  - Sources and fate of organic matter in constructed versus natural coastal
      waterways.
AB  - Coastal wetlands are increasingly being converted into canal estates with
      potential consequences for ecosystem functioning. We compared the sources and
      fate of organic matter and water quality at four types of canal habitats
      (entrances and ends of canals, canal lakes and lake edges) and shallow and deep
      natural habitats (four replicates of each habitat). The fate of labile organic
      matter was assessed by measuring rates of scavenging of carrion. Surface
      sediments were analysed for organic carbon content and stable carbon isotopes,
      fatty acid biomarkers and compound specific stable isotope analysis of selected
      fatty acids were used to elucidate sources of sedimentary organic matter. Canal
      lakes differed from other habitats and were characterised by negligible
      scavenging, larger quantities of organic matter comprised of higher contributions
      from diatoms, and hypoxia. Despite some trends, natural habitats were
      statistically indistinguishable from canal entrances and ends. Variation among
      replicate habitats was large.

PMID- 30301067
TI  - Whole genome sequences to assess the link between antibiotic and metal resistance
      in three coastal marine bacteria isolated from the mummichog gastrointestinal
      tract.
AB  - Antibiotic resistance is a global public health issue and metal exposure can co
      select for antibiotic resistance. We examined genome sequences of three multi
      drug and metal resistant bacteria: one Shewanella sp., and two Vibrio spp.,
      isolated from the gut of the mummichog fish (Fundulus heteroclitus). Our primary
      goal was to understand the mechanisms of co-selection. Phenotypically, the
      strains showed elevated resistance to arsenate, mercury, and various types of
      beta-lactams. The genomes contained genes of public health concern including one
      carbapenemase (blaOXA-48). Our analyses indicate that the co-selection phenotype
      is mediated by chromosomal resistance genes and cross-resistance. No evidence of
      co-resistance was found; most resistance genes were chromosomally located.
      Moreover, the identification of many efflux pump gene homologs indicates that
      cross-resistance and/or co-regulation may further contribute to resistance. We
      suggest that the mummichog gut microbiota may be a source of clinically relevant
      antibiotic resistance genes.

PMID- 30301068
TI  - Impacts of the traditional baited basket fishing trap "gargoor" on green sea
      turtles Chelonia mydas (Testudines: Cheloniidae) Linnaeus, 1758 from two case
      reports in the United Arab Emirates.
AB  - The United Arab Emirates fisheries consist of highly diverse fish communities,
      and the most popular equipment used by fishermen to harvest them is a traditional
      baited basket fishing trap known locally as "gargoor". Gargoors are dome-shaped
      traps made from galvanized steel; they have a circular supporting base and a
      funnel-like entrance. Unintended impacts of gargoors on marine fauna include
      bycatch of non-target species and, when lost, ghost fishing. However, there is
      very little information on sea turtle interaction with gargoors. In this paper we
      present two case reports from the eastern coast of the UAE of green sea turtle
      strandings associated with gargoor interactions. The first case report describes
      a turtle that was discovered trapped inside a lost or abandoned gargoor. The
      second case report describes another turtle that suffered from extensive
      perforation of the gastrointestinal tract resulting from the ingestion of 32
      pieces of rusty gargoor fragments.

PMID- 30301069
TI  - Analyzing trends in ballasting behavior of vessels arriving to the United States
      from 2004 to 2017.
AB  - Maritime shipping transports over 90% of global goods. Ballast water, used to
      provide vessel stability, has been associated with the introduction of marine
      invasive species. Thus, understanding ballasting trends is imperative to
      protecting human and environmental health. This paper examines data from the
      National Ballast Information Clearinghouse to assess ballasting behavior and
      shipping trends in the United States. From 2005 to 2017, vessel arrivals have
      remained relatively constant (annual growth rate of 1.2% per year) while total
      ballast discharge per vessel has grown at an annual rate of 7.6%. Furthermore,
      from 2014 to 2016, alternative ballast water management methods have been on the
      rise, and these treatment options are likely to continue increasing in response
      to the International Maritime Organization Ballast Water Management Convention
      that entered into force in September 2017. It is critical that the shipping
      industry monitors potential cascading impacts on other ballasting behaviors
      stemming from this shift.

PMID- 30301070
TI  - The impact of ghost fishing on catch rate and composition in the southern Caspian
      Sea.
AB  - The catch rates and the catch composition of lost nets were investigated during
      two seasons (fall and winter) in the southern Caspian Sea. A total of 167 surveys
      were conducted using anchor to retrieve ghost nets, which led to recover a total
      of 515 monofilaments gillnet. The most abundant caught species in during both
      seasons was belonged to Alosa caspia (52.1-43.9%). At both seasons, individuals
      of Huso huso, and Acipenser stellatus were substantially caught below the length
      at first maturity. The highest mean of catch rates was discovered at 0-10 m depth
      (2.79 kg), while the depth of 10-20 m provided the lowest amount of catch (2.0
      kg). The Spearman correlation test showed that an increase in depth is reflected
      in lower values of the retrieved ghost nets. Overall, this study revealed that
      ghost gillnets is widely distributed in the southern Caspian Sea, mainly at the
      shallow waters.

PMID- 30301071
TI  - Aragonite saturation state variation and control in the river-dominated marginal
      BoHai and Yellow seas of China during summer.
AB  - Based on a survey conducted from June to July 2013, aragonite saturation state
      variation and control in the river-dominated marginal BoHai and Yellow seas were
      investigated. Surface water Omegaarag ranged from 2.0-3.8, whereas subsurface
      water Omegaarag was generally lower than 2.0. Temperature changes had a strong
      influence on Omegaarag through induced CO2 solubility changes in seawater.
      Riverine freshwater input decreased Omegaarag in the Changjiang and Yalu river
      estuaries, but induced higher Omegaarag in the Yellow River estuary. Biological
      processes had opposite effects on Omegaarag, whereby elevated biological
      production led to the highest Omegaarag in the South Yellow Sea surface water,
      whereas net community respiration/remineralization induced low Omegaarag in
      subsurface water. Stratification affected the level and scale of low Omegaarag in
      subsurface water. By the year 2100, surface water with Omegaarag > 2.0 will
      disappear except for the Yellow River estuary, and most of the subsurface water
      will develop substantial aragonite undersaturation.

PMID- 30301072
TI  - Marine debris ingestion of green sea turtles, Chelonia mydas, (Linnaeus, 1758)
      from the eastern coast of the United Arab Emirates.
AB  - The deleterious effects of marine debris ingestion on marine turtles are well
      documented in literature globally. In this study, the qualitative and
      quantitative aspects of marine debris ingested by 14 stranded green sea turtles
      Chelonia mydas, (Linnaeus, 1758) along the eastern coast of the United Arab
      Emirates were investigated. The numeric and gravimetric proportions of debris in
      the esophagus, stomach and intestines were documented following classification of
      color, presumed sources and Marine Strategy Framework Directive categories and
      sub-categories. The results show that 85.7% of the specimens examined consumed
      marine debris. On average, specimens consumed 61.9 +/- 17.2 items of 1.0 +/- 0.3
      g mass. Plastics, particularly white, and transparent thread-like and sheet-like
      plastics, were the predominant debris ingested. The results reflect a potentially
      high level of interaction between green sea turtles and anthropogenic marine
      debris along the Gulf of Oman coast of the UAE.

PMID- 30301073
TI  - Marginal coral reefs show high susceptibility to phase shift.
AB  - Phase shift, resulting from coral reef degradation, has been frequently recorded
      on reefs in optimal conditions, while marginal reefs were considered more
      resistant due to few records. Noting the lack of marginal reef phase shift
      studies, we quantitatively assessed their geographic extent in the Southwest
      Atlantic. Using metadata and a calculated phase shift index, we identified phase
      shifts from corals to both zoanthid and macroalgal dominance. Positive
      correlations existed between phase shift and local human impacts for zoanthids:
      proximity to human populations >100,000 inhabitants, urbanized surfaces and
      dredged ports and a negative relationship to the endurance of SST >1  degrees C
      above normal. Macroalgal shifts positively correlated to ports and urbanized
      surfaces, higher latitudes and shore proximity, indicating a possible link to
      nutrient runoff. The high frequency of these phase shifts suggests greater
      degradation than reported for Caribbean reefs, suggesting that marginal reefs do
      not have higher natural resistance to human impacts.

PMID- 30301074
TI  - Characteristics of phytoplankton assemblages in the southern Yellow Sea, China.
AB  - The characteristics of phytoplankton assemblages were analyzed by the Utermohl
      method in the southern Yellow Sea in summer, 2008. A total of 113 species
      (including varieties and forms), belonging to 51 genera and 3 phyla, were
      identified. Diatom was the most dominant group. The dominant species included
      Eucampia zoodiacus, Leptocylindrus danicus, Chaetoceros affinis, Thalassionema
      nitzschioides, Skeletonema costatum, Paralia sulcata and Chaetoceros tortissimus,
      which were eurytopic and temperate species. The cell abundance of phytoplankton
      ranged from 0.04 to 620.08 cells.mL-1 with an average of 27.52 cells.mL-1.
      Horizontally, the cell abundance showed a decreasing trend from the south to the
      north. In terms of vertical distribution, the values in surface and subsurface
      water layers were higher than those in bottom water layers. Results of
      correlation analysis showed that phytoplankton cell abundance was positively
      correlated with water temperature, ammonia and nitrite concentrations, and
      negatively correlated with salinity and silicate concentration.

PMID- 30301075
TI  - On the transport and modeling of dispersed oil under ice.
AB  - Theoretical arguments and numerical investigations were conducted to understand
      the transport of oil droplets under ice. It was found that the boundary layer
      (BL) in the water under ice produces a downward velocity that reaches up to 0.2%
      of horizontal current speed, and is, in general, larger than the rise velocity of
      70 MUm oil droplets. The eddy diffusivity was found to increase with depth and to
      decrease gradually afterward. Neglecting the gradient of eddy diffusivity when
      conducting Lagrangian transport of oil droplets would result in an unphysical
      spatial distribution. When the downward velocity of water was neglected, oil
      accumulated at the water-ice interface regardless of the attachment efficiency.
      The lift force was found to scrape off droplets of the ice, especially for
      droplets <= 70 MUm. These findings suggest that previous oil spill simulations
      may have overestimated the number of small droplets (<=70 MUm) at the water-ice
      interface.

PMID- 30301076
TI  - Sorption behaviors of tris-(2,3-dibromopropyl) isocyanurate and
      hexabromocyclododecanes on polypropylene microplastics.
AB  - In recent years, microplastics in oceans have become a serious environmental
      problem and the focus of attention. In the present study, the sorption of TBC and
      HBCDs by microplastics in simulated seawater is examined. The effects of particle
      size, temperature, salinity, and concentration on the adsorption of TBC and HBCDs
      by microplastics are studied. Results indicate that the first-order adsorption
      kinetic model is more suitable than the pseudo-second-order kinetic model to
      describe adsorption. The equilibrium adsorption times are 15 h and 10 h for TBC
      and HBCDs, respectively. The adsorption capacity increases with the decrease in
      particle size. The adsorption capacity gradually increases at first and then
      decreases with the increase in salinity and temperature. The maximum adsorption
      capacity is at 15  degrees C and 14% salinity. Compared with the linear and
      Freundlich models, the Langmuir model is more suitable; this indicates that the
      main adsorption mechanism might be chemical adsorption.

PMID- 30301077
TI  - Scleractinian coral microplastic ingestion: Potential calcification effects, size
      limits, and retention.
AB  - The impact that microplastics (<5 mm) have on scleractinian coral is largely
      unknown. This study investigated calcification effects, size limits, and
      retention times of microbeads and microfibers in two Caribbean species,
      Montastraea cavernosa and Orbicella faveolata, in a series of three experiments.
      No calcification effects were seen in the two-day exposure to a microbead
      concentration of 30 mg L-1. M. cavernosa and O. faveolata actively ingested
      microbeads ranging in size from 425 MUm-2.8 mm, however, a 212-250 MUm size class
      did not elicit a feeding response. The majority of microbeads were expelled
      within 48 h of ingestion. There was no difference in ingestion or retention times
      of 425-500 MUm microbeads versus 3-5 mm long microfibers. M. cavernosa and O.
      faveolata have the ability to recognize and reject indigestible material, yet,
      there is still a need to study effects of energetics and microplastic
      contamination as a result of ingestion and egestion.

PMID- 30301078
TI  - Highly polluted life history and acute heat stress, a hazardous mix for blue
      mussels.
AB  - Intertidal sessile organisms constitute through their life history unintended
      stress recorders. This study focuses on the impact of pollution on Mytilus edulis
      ability to cope with an additional stress. For this purpose, two acclimation
      stages to different temperatures were conducted before an acute stress exposure
      in mussels collected from a heavily polluted site. Gill proteomes were analyzed
      by 2DE and regulated proteins identified. Massive mortality was observed for
      organisms acclimated to colder temperatures. Despite this major difference, both
      groups shared a common response with a strong representation of proteoforms
      corresponding to "folding, sorting and degradation" processes. Nevertheless,
      surviving mussels exhibit a marked increase in protein degradation consistent
      with the observed decrease of cell defense proteins. Mussels acclimated to warmer
      temperature response is essentially characterized by an improved heat shock
      response. These results show the differential ability of mussels to face both
      pollution and acute heat stress, particularly for low-acclimated organisms.

PMID- 30301079
TI  - Sources and trends of artificial sweeteners in coastal waters in the bay of Cadiz
      (NE Atlantic).
AB  - This is the first comprehensive study on the input, occurrence, and distribution
      of artificial sweeteners (ASs) in coastal wastewater treatment plants (WWTPs) and
      their receiving coastal waters. Acesulfame (ACE), aspartame (ASP), cyclamate
      (CYC), saccharine (SAC), and sucralose (SUC) were monitored for 6 months in Cadiz
      Bay (SW Spain). ASP was always detected at <0.1 MUg L-1 and removal efficiencies
      were >90% for SAC and CYC. Higher ACE removal efficiencies were observed during
      warmer months. Persistence of ACE and SUC was observed in both WWTPs and their
      receiving coastal surface waters, where values up to 0.6 and 3 MUg L-1 were
      measured, respectively. The highest concentrations were measured in a sewage
      impacted estuary located in the north of the bay, where conservative behavior was
      confirmed. The source specificity and recalcitrance of ACE and SUC make them
      suitable for being used as sewage-pollution markers in coastal environments.

PMID- 30301080
TI  - Carbon economy of Mediterranean seagrasses in response to thermal stress.
AB  - Increased plant mortality in temperate seagrass populations has been recently
      observed after summer heatwaves, although the underlying causes of plant death
      are yet unknown. The potential energetic constrains resulting from anomalous
      thermal events could be the reason that triggered seagrass mortality, as
      demonstrated for benthic invertebrates. To test this hypothesis, the carbon
      balance of Posidonia oceanica and Cymodocea nodosa plants from contrasting
      thermal environments was investigated during a simulated heatwave, by analyzing
      their photosynthetic performance, carbon balance (ratio
      photosynthesis:respiration), carbohydrates content, growth and mortality. Both
      species were able to overcome and recover from the thermal stress produced by the
      six-week exposure to temperatures 4  degrees C above mean summer levels, albeit
      plants from cold waters were more sensitive to warming than plants from warm
      waters as reflected by their inability to maintain their P:R ratio unaltered. The
      strategies through which plants tend to preserve their energetic status varied
      depending on the biology of the species and the thermal origin of plants. These
      included respiratory homeostasis (P. oceanica warm-plants), carbon diversion from
      growth to respiration (C. nodosa cold-plants) or storage (P. oceanica warm
      plants) and changes in biomass allocation (C. nodosa warm-plants). Findings
      suggest an important geographic heterogeneity in the overall response of
      Mediterranean seagrasses to warming with potential negative impacts on the
      functions and services offered by seagrass meadows including among others their
      capacity for carbon sequestration and carbon export to adjacent ecosystems.

PMID- 30301081
TI  - Litter & microplastics features in table salts from marine origin: Italian versus
      Croatian brands.
AB  - This study estimates litter content, including microplastics, mesoplastic, and
      macroplastic in marine table salts coming from Italy and Croatia. Both high (HC)
      and low (LC) costs commercial brands easily found at the supermarket were
      analysed. Any macroplastic or mesoplastic were recovered while microplastics and
      other litter impurities significantly affect table salts of all tested brands.
      Average microplastic values ranged within 1.57 (HC) - 8.23 (LC) (Italy) and 27.13
      (HC) - 31.68 (LC) items/g (Croatia). Microplastics sizes (min-max) ranged within
      4-2100 MUm (Italy) and 15-4628 MUm (Croatia). In samples from both Nations, a
      significant general positive correlation between the average number of items/g
      recorded and the total amount of general impurities was recorded. Concerning
      microplastic shapes, in Italy, fragments dominated even if fibres, granules,
      films, and foams are frequently recorded. On the contrary, clear PP fibres
      dominated in Croatian brands even if also other shape classes were recorded.

PMID- 30301082
TI  - The effects of plastic bags presence on a macrobenthic community in a polluted
      estuary.
AB  - The damaging effects of marine debris on wildlife are often noted through the
      observation of animals that ingest and/or become entangled in debris. Yet, few
      studies have evaluated the effects of marine litter on benthic habitats. The aim
      of this study was to investigate if the presence of plastic bags has any effect
      on benthic macrofauna in an estuary located in an urban area in North-eastern
      Brazil. Biogeochemical and macrofauna samples were obtained from 10 different
      deposition locations (location factor), under, border and distant (treatment
      factor) from plastic bags. The results did not show any significant alterations
      in the biogeochemical parameters of the sediment due to treatment effect except
      for summed microphytobenthic pigments. The macrobenthic community structure
      responded to treatment. The greatest dissimilarity (34%) was between samples that
      were under and distant. Effects occurred despite the high dynamics of deposition
      resuspension of plastic bags and the dominance of opportunistic species. Changes
      in community structure are a complex result of plastic bags effects on species
      ecological interactions in the polluted estuarine environment, attracting deposit
      feeders, diminishing suspension feeders and providing mechanical protection
      against predation by seabirds.

PMID- 30301084
TI  - Sex may influence environmental diphenhydramine accumulation in Round Stingrays.
AB  - Despite the amount of treated wastewater discharged into the Southern California
      Bight, few studies have examined pharmaceutical compounds in local biota. The
      Round Stingray (Urobatis halleri) was selected as a representative elasmobranch
      species to perform an exploratory study on environmental pharmaceutical exposure.
      Archived liver samples of males and females from juvenile to adult size classes
      from several locations (n = 53) were examined for 18 pharmaceutical and illicit
      drug compounds using isotope-dilution LC-MS/MS. Very few compounds were detected
      in stingray livers, with diphenhydramine as the only pharmaceutical above
      quantitation limits. Only stingrays collected from the urban site (mainland
      California) had detectable levels of diphenhydramine compared to no detections in
      reference stingrays (offshore island). Sex and sampling location substantially
      influenced both detection rate and concentrations. Our results suggest that
      aspects of species' ecology and physiology should be considered for future
      studies investigating pharmaceutical exposure in elasmobranchs.

PMID- 30301083
TI  - Exceptional biodiversity of the cryptofaunal decapods in the Chagos Archipelago,
      central Indian Ocean.
AB  - The Chagos Archipelago is geographically remote and isolated from most direct
      anthropogenic pressures. Here, we quantify the abundance and diversity of decapod
      crustaceans inhabiting dead coral colonies, representing a standardised
      microhabitat, across the Archipelago. Using morphological and molecular
      techniques we recorded 1868 decapods from 164 nominal species within 54 dead
      coral colonies, but total species estimates (Chao1 estimator) calculate at least
      217 species. Galatheids were the most dominant taxa, though alpheids and
      hippolytids were also very abundant. 32% of species were rare, and 46% of species
      were found at only one atoll. This prevalence of rarer species has been reported
      in other cryptofauna studies, suggesting these assemblages maybe comprised of low
      abundance species. This study provides the first estimate of diversity for reef
      cryptofauna in Chagos, which will serve as a useful baseline for global
      comparisons of coral reef biodiversity.

PMID- 30301086
TI  - The response of benthic foraminifera to aquaculture and industrial pollution: A
      case study from the Northern Persian Gulf.
AB  - The aquaculture and industrial sewage impacts on benthic foraminifera
      investigated at two reefs across the northern Persian Gulf. The foraminifera
      assemblages at a single sewaged reef were compared with two non-sewaged reefs. A
      low-diversity assemblage, dominated by stress-tolerant species Quinqueloculina
      sp. and larger symbiont-bearing Amphistegina sp., was characteristic of the
      industrial sewaged reef. The opportunistic species Ammonia sp. and Elphidium sp.
      were common in aquaculture sewaged reef. The density of foraminifera in sewaged
      reefs was lower than non-sewaged reefs. The lower diversity was only detected in
      the industrial sewaged reef. Assemblage structure was significantly different
      between sewaged and non-sewaged reefs. The industrial sewaged reef displayed high
      FORAM Index values (>4.0), reflecting favorable environments for supporting
      relatively healthy reefs. FORAM Index in aquaculture sewaged reef ranged from 2.0
      to 4.0 indicated that the water with organic pollution may support living coral
      community, but any damage would not be followed by recovery.

PMID- 30301085
TI  - Urban coral reefs: Degradation and resilience of hard coral assemblages in
      coastal cities of East and Southeast Asia.
AB  - Given predicted increases in urbanization in tropical and subtropical regions,
      understanding the processes shaping urban coral reefs may be essential for
      anticipating future conservation challenges. We used a case study approach to
      identify unifying patterns of urban coral reefs and clarify the effects of
      urbanization on hard coral assemblages. Data were compiled from 11 cities
      throughout East and Southeast Asia, with particular focus on Singapore, Jakarta,
      Hong Kong, and Naha (Okinawa). Our review highlights several key characteristics
      of urban coral reefs, including "reef compression" (a decline in bathymetric
      range with increasing turbidity and decreasing water clarity over time and
      relative to shore), dominance by domed coral growth forms and low reef
      complexity, variable city-specific inshore-offshore gradients, early declines in
      coral cover with recent fluctuating periods of acute impacts and rapid recovery,
      and colonization of urban infrastructure by hard corals. We present hypotheses
      for urban reef community dynamics and discuss potential of ecological engineering
      for corals in urban areas.

PMID- 30301087
TI  - Antibiotic and heavy-metal resistance of Vibrio parahaemolyticus isolated from
      oysters in Korea.
AB  - Vibrio parahaemolyticus, found frequently in oysters and other seafoods, is the
      most prevalent gastroenteritis-causing pathogen in Korea and other Asian
      countries. It is associated exclusively with the consumption of raw or improperly
      cooked contaminated seafood, especially oysters. In this study, we isolated and
      characterized 59 V. parahaemolyticus strains (toxR-positive) from May to October
      2016 in shellfish-harvesting areas off the west coast of Korea. The results
      revealed that none of the isolates contained the tdh and trh toxicity genes. The
      multiple antibiotic resistance (MAR) value of most isolates was 0.32, but it was
      as high as 0.69 in one isolate strain. Moreover, when resistance to heavy metals
      was examined, the majority of the isolates displayed resistance to Ba2+ (98.3%),
      Co3+ (28.8%), Cd2+ (16.9%), and Cu2+ (13.6%). Interestingly our data revealed
      that tolerance to heavy metals was prevalent in the V. parahaemolyticus strains
      with more than two antibiotic resistance phenotypes.

PMID- 30301088
TI  - Increased temperature but not pCO2 levels affect early developmental and
      reproductive traits of the economically important habitat-forming kelp Lessonia
      trabeculata.
AB  - The effects of ocean warming and ocean acidification on developmental and
      reproductive traits of Lessonia trabeculata were evaluated. Meiospores were
      cultured for 35 days in an experimental mesocosm where temperature (~15 and 19 
      degrees C) and partial CO2 pressure (pCO2, ~400 and 1300 MUatm) were controlled.
      The results indicate that germination was reduced at 19  degrees C, whereas the
      increase of pCO2 only had effects at 15  degrees C. Likewise, the increase in
      temperature significantly affected the vegetative growth of female gametophytes.
      Sex ratio was not affected significantly by any of the variables studied.
      Fertility and reproductive success decreased by about 50% at 19  degrees C. The
      pCO2 levels had no significant effects on most early developmental traits. The
      results suggest that ocean warming or periodic warming events (e.g. an El Nino
      event) might affect the recruiting capacity of this or other similar species by
      affecting their early developmental stages.

PMID- 30301089
TI  - The effects of dredging and environmental conditions on concentrations of
      polycyclic aromatic hydrocarbons in the water column.
AB  - Sediment dredging can cause damage to the marine environment due to mobilization
      of sediments and contaminants. The effects of dredging and boundary environmental
      conditions on the concentration of Polycyclic Aromatic Hydrocarbons (PAHs) in
      water were evaluated during dredging of the Oil Port of Genoa-Multedo (Italy).
      Results showed that turbidity and PAH concentrations increased in the water
      during dredging. However, the scenario was complex due to the high number of
      interacting physical-chemical factors influencing PAH concentrations and
      transport. Due to these, PAH distribution is different in water, where low
      molecular-weight PAHs were predominant (maximum concentration 0.105 MUg L-1), and
      in bottom sediments, where high-molecular-weight PAHs had the highest
      concentrations (from 299.3 to 1256.5 ng g-1). Moreover, mainly during dredging
      the PAH concentrations in water were significantly higher inside than outside the
      port as a consequence of the lower dynamics within the port basin. Turbidity was
      the main parameter related to PAH concentrations.

PMID- 30301090
TI  - Evaluating the impact of sewage discharges on the marine environment with a
      lightweight AUV.
AB  - Environmental studies that use small Autonomous Underwater Vehicles (AUVs) can
      survey wider and deeper areas, compared to traditional methods, at a reasonable
      cost. Thanks to the precise vehicle navigation systems, the data collected can be
      accurately geolocalized. Besides, lightweight vehicles can be deployed from the
      shore or from small boats and programmed by means of user-friendly graphical
      interfaces, thus reducing and simplifying the need of human resources and
      infrastructures. Based on such a technology, this paper presents a framework to
      assess the environmental impact of a marine sewage outfall set in the Bay of
      Palma (Mallorca, Spain). We report the results of the analysis of the images
      recorded in the course of six missions conducted with an AUV. The plan was
      designed after a microbiological analysis detected the presence of cyanobacteria
      in a sample of sand and water collected by scuba divers close to the sewer pipe
      mouth.

PMID- 30301091
TI  - Calculation of oil droplet size distribution in ocean oil spills: A review.
AB  - Calculation of oil droplet size distribution is one of the key components of
      ocean oil spill models. Oil fate and transport calculations of the model are
      significantly impacted by the droplet size distribution. Accuracy of the model
      predictions heavily depend on how well the model can calculate or represent oil
      droplet sizes. However, in early oil spill models, the importance of oil droplet
      size calculation has been overlooked and they used simple empirical formulas. In
      recent decades, there have been some significant improvements in understanding of
      oil droplet size calculations. Both experimental studies as well as numerical
      studies have been contributed to improve oil droplet size calculations. The
      traditional equilibrium models have been improved while droplet dynamics models
      provided a different dimension to the oil DSD calculations. Thus, at this stage
      it is important to review the existing studies and methods of oil droplet size
      calculation. The objective of this paper is to review the development of oil
      droplet size calculation in ocean oil spill models highlighting the recent
      improvements. Furthermore, this paper discusses the capabilities and limitations
      of different approaches in calculating oil droplet size distribution in both
      underwater and surface oil spill models and discuss their applicability to
      different situations. This study will provide a good guideline for future oil
      spill model developments to improve the oil droplet size calculations.

PMID- 30301093
TI  - Oil and gas infrastructure decommissioning in marine protected areas: System
      complexity, analysis and challenges.
AB  - Many offshore oil and gas production facilities are nearing the end of their
      operational life, with decommissioning now becoming a global challenge. The
      compatibility of decommissioning operations to marine protected areas (MPAs)
      creates further challenges. The recently-developed DAPSI(W)R(M) problem
      structuring framework (covering Drivers, Activities, Pressures, State changes,
      Impacts (on Welfare) and Responses (as Measures)) was applied here to interrogate
      the complexity of decommissioning oil and gas infrastructure within MPAs, with
      outputs feeding into the development of a novel database tool for Screening
      Potential Impacts of Decommissioning Activities (SPIDA). In meeting the current
      requirements of the marine regulatory regime, SPIDA provides a more streamlined,
      evidence-based process which can be applied by industry, statutory nature
      conservation bodies and regulators for identifying and evaluating evidence that
      supports the implications of decommissioning alternatives on the condition of
      MPAs. SPIDA has been developed to be adapted for other activities and sectors,
      including offshore renewables.

PMID- 30301092
TI  - Marine animal forests as useful indicators of entanglement by marine litter.
AB  - Entanglement of marine fauna is one of the principal impacts of marine litter,
      with an incidence that can vary strongly according to regions, the type and the
      quantity of marine litter. On the seafloor, areas dominated by sessile suspension
      feeders, such as tropical coral reefs or deep-sea coral and sponge aggregations,
      have been termed "animal forests" and have a strong potential to monitor the
      temporal and spatial trends of entanglement by marine litter, especially fishing
      gears. Several characteristics of these organisms represent advantages while
      avoiding constraints and bias. Biological constraints and logistical aspects,
      including tools, are discussed to better define a strategy for supporting long
      term evaluation of accumulation and entanglement of marine litter.

PMID- 30301094
TI  - Mercury and selenium in the grass goby Zosterisessor ophiocephalus (Pisces:
      Gobiidae) from a mercury contaminated Mediterranean lagoon.
AB  - Mercury (Hg) and its bioaccumulation are important in evaluating the health risk
      through fish consumption. In the Marano and Grado Lagoon a historical
      contamination originating from both mining and industrial sources is present. In
      this study the Hg levels in the grass goby and the protective effect of selenium
      (Se) were determined as a function of size, sex, sampling sites and season.
      Mercury often exceeded the limit for commercialisation, whereas Se was mostly
      constant being homeostatically regulated. The mean Se/Hg molar ratio showed about
      40% of data >1.0 and the HBVSe index was on average equal to 0.0. Thus, grass
      goby of this area is not a Se source food indicated for pregnant and/or
      breastfeeding women, but its occasional consumption would appear to have no
      contraindications if integrated with other Se rich foods: the ingestion of about
      10 fish fillets per week can be safely consumed by adults.

PMID- 30301095
TI  - Petroleum hydrocarbon and microbial community structure successions in marine oil
      related aggregates associated with diatoms relevant for Arctic conditions.
AB  - Oil-related aggregates (ORAs) may contribute to the fate of oil spilled offshore.
      However, our understanding about the impact of diatoms and associated bacteria
      involved in the formation of ORAs and the fate of oil compounds in these
      aggregates is still limited. We investigated these processes in microcosm
      experiments with defined oil dispersions in seawater at 5  degrees C, employing
      the Arctic diatom Fragilariopsis cylindrus and its associated bacterial
      assemblage to promote ORA formation. Accumulation of oil compounds, as well as
      biodegradation of naphthalenes in ORAs and corresponding water phases, was
      enhanced in the presence of diatoms. Interestingly, the genus Nonlabens was
      predominating the bacterial communities in diatom-supplemented microcosms, while
      this genus was not abundant in other samples. This work elucidates the relevance
      of diatom biomass for the formation of ORAs, microbial community structures and
      biodegradation processes in chemically dispersed oil at low temperatures relevant
      for Arctic conditions.

PMID- 30301096
TI  - Polycyclic aromatic hydrocarbons in sediments of the Amazon River Estuary (Amapa,
      Northern Brazil): Distribution, sources and potential ecological risk.
AB  - The distribution, sources and potential ecological risk of priority polycyclic
      aromatic hydrocarbons (PAHs) in sediment from the Amazon River Estuary (Macapa
      and Santana, Amapa, Northern Brazil) were investigated. The total PAHs
      concentration (?PAH) ranged from 22.2 to 158.9 ng g-1 dw (mean value 49.4 ng g-1
      dw). PAHs levels in the study area were relatively low than those in nearby areas
      and other coastal zones worldwide, and could be considered as baseline for PAHs
      in Amazonic sediments. PAHs ratios and the statistical analysis showed that
      fossil fuel and biomass combustions, primarily from local sources, were the
      dominant PAHs origins. The potential ecological risk was assessed on the basis of
      the sediment quality guidelines, and it was found that PAHs in the sediments of
      the Amazon River Estuary do not cause adverse effects on living organisms;
      however, the abundance of naphthalene and the presence of dibenzo[a,h]anthracene
      and benzo[a]pyrene deserve more attention.

PMID- 30301097
TI  - Environmental triggers of a Microcystis (Cyanophyceae) bloom in an artificial
      lagoon of Hangzhou Bay, China.
AB  - The relationship between Microcystis abundance and environmental variables was
      studied during a Microcystis bloom in the summer months of 2016 in an artificial
      lagoon of Hangzhou Bay, China. It was determined that Microcystis abundance
      increased from 0.16 * 104 cell/L to 5.8 * 107 cell/L within 17 days from 28 July
      to 14 August, contributing to 96.84-99.56% of the total phytoplankton abundance.
      Then, Microcystis gradually disappeared 57 days afterwards. The results showed
      that the growth of Microcystis, including the stage of recovery, outbreak,
      subsidence and disappearance, was significantly correlated with water
      temperature, salinity, soluble reactive phosphorus (PO4-P), dissolved inorganic
      nutrients (DIN), silicate (SiO4-Si), the ratio of DIN/SiO4-Si and zooplankton
      abundance, and the key environmental triggers which promoted the outbreak of
      Microcystis were water temperature, PO4-P concentration and zooplankton abundance
      in this artificial lagoon.

PMID- 30301098
TI  - Mercury contents in relation to biometrics and proximal composition and
      nutritional levels of fish eaten from the Western Mediterranean Sea (Almeria
      bay).
AB  - Total liver and muscle mercury, and muscular composition, biometrics and trophic
      levels, were determined in four species (Mullus surmuletus, Merluccius
      merluccius, Auxis rochei and Scomber japonicus) of the Mediterranean Sea (Almeria
      Bay, Spain). Mercury levels did not exceed the maximum residue limit, and M.
      merluccius obtained the highest level in muscle. Considerable variations in Hg
      content among individuals were observed in non-gregarious species. A positive
      correlation between Hg and trophic level or length was found in muscle, but not
      in liver. Organs (liver or muscle) with major Hg accumulation depend on species;
      muscle in M. merluccius and liver in S. japonicus. The results indicate that Hg
      levels in fish depend on intra- and interspecies factors that should be taken
      into account in systems to monitor Hg levels.

PMID- 30301099
TI  - Spatial variation of heavy metals in sediments within a temperate mangrove
      ecosystem in northern New Zealand.
AB  - Spatial dynamics of heavy metals (Cd, Cu, Fe, Pb, and Zn) and metalloid As were
      investigated along the sedimentary column, inside and outside mangrove stands,
      and within the upper, middle, and lower Mangawhai Estuary, New Zealand. Organic
      matter contents (1.89 to 17.15%) were 10 times higher inside versus outside
      mangroves, and decreased sharply with depth to 30 cm. Cu, Fe, and Zn were highest
      in the upper estuary and Pb was highest close to a road (lower estuary),
      reflecting road run-off. A mangrove island (lower estuary; high energy) had
      lowest heavy metal and highest As concentrations (resulting from high absorption
      of As by the carbonate rich sediments). Most of the analysed sediment parameters
      in our study were higher inside versus outside mangroves, suggesting the
      accumulation of organic matter and build up capacity to buffer pollutants. Our
      results show that mangrove stands tend to accumulate heavy metals and may act as
      natural filters of pollution of coastal waterways.

PMID- 30301100
TI  - Study on the bacterial and archaeal community structure and diversity of
      activated sludge from three wastewater treatment plants.
AB  - In this study, the bacterial and archaeal communities along with their functions
      of activated sludge from three wastewater treatment plants were investigated by
      Illumina MiSeq Platform. The treatment processes were modified A/A/O, DE
      oxidation ditch and pre-anaerobic carrousel oxidation ditch, respectively. The
      taxonomic analyses showed that Proteobacteria was the predominant bacterial
      phylum, and Nitrosospira was the dominant nitrification genus. Candidatus
      Accumulibacter was abundant in DE oxidation ditch process, and the main archaea
      communities were methanosaeta-like species which had the capability to anaerobic
      ammonia oxidation. The results illustrated that anaerobic ammonium oxidation
      played an important role in the nitrogen metabolism and there might be other
      unknown phosphate-accumulating organisms (PAOs) performing phosphorus removal in
      activated sludge. The predicted function analyses indicated that both bacteria
      and archaea were involved in nitrification, denitrification, ammonification and
      phosphorus removal processes, and their relative abundance varied metabolic
      modules differed from each other.

PMID- 30301102
TI  - Passive sampling monitoring of PAHs and trace metals in seawater during the
      salvaging of the Costa Concordia wreck (Parbuckling Project).
AB  - Passive sampling techniques were used for monitoring trace metals and polycyclic
      aromatic hydrocarbons (PAHs) in the seawater surrounding the Costa Concordia
      shipwreck (Isola del Giglio, Italy). The monitoring lasted two and a half years
      (2012-2014) and considered all four phases of the "parbuckling project":
      stabilisation of the wreckage, installation of steel caissons on both sides of
      the wreck, parbuckling, and refloating. Dissolved trace metals (Cd, Cr, Cu, Hg,
      Ni, Pb, and V) were measured with diffusive gradients in thin films (DGT), while
      freely dissolved PAHs were measured with semi-permeable membrane devices (SPMDs).
      Passive sampling allowed to detect very low concentrations of contaminants, and
      indicated significant differences among the sampling stations and among the
      different steps for salvaging the wreck. The results suggested that the main
      source of contamination was the heavy working vessel traffic at the disaster
      site, rather than the release of contaminants from the wreck.

PMID- 30301101
TI  - Sources and scavenging of plutonium in the East China Sea.
AB  - The 240Pu/239Pu atom ratio and 239+240Pu activity of seawater in the East China
      Sea (ECS) was measured in order to examine the Pu sources and elaborate Pu
      scavenging process. High 240Pu/239Pu atom ratios (0.187-0.243, average = 0.221 +/
      0.017) in the surface water and water column were observed during 2011, implying
      of non-global fallout Pu sources. The distribution of 240Pu/239Pu atom ratio in
      the ECS was in agreement with the introduction pathway of the Kuroshio, showing a
      decreasing trend away from the outer shelf. An even higher 240Pu/239Pu atom
      ratios (0.243-0.263, average = 0.253 +/- 0.007) were observed in the Kuroshio,
      indicating the non-global fallout Pu signal from the Pacific Proving Grounds
      (PPG). Using a two end-member mixing model, the Pu source from the PPG
      contribution was calculated to be 36 +/- 9% in the ECS seawater. The 239+240Pu
      activities of surface seawater were in the range of 2.00-2.95 mBq m-3 in the ECS.
      The spatial distribution of 239+240Pu activity in the surface seawater showed an
      increasing trend from the outer shelf to the nearshore. Moreover, 239+240Pu
      inventory of water column at the station DH23 in the ECS was calculated to be
      ~0.29 Bq m-2, which was 1-3 orders of magnitude lower than the estimates of
      sediment cores in the ECS shelf (9-407 Bq m-2). Such differences were determined
      by the high degree Pu scavenging efficiency in the ECS and high Pu input carried
      by terrestrial sediments from the Yangtze River. Finally, both 240Pu/239Pu atom
      ratios and 239+240Pu activities were identical before and after the Fukushima
      nuclear accident (FNA), suggesting that the impact of the FNA on the ECS was
      negligible.

PMID- 30301103
TI  - PAHs contamination in edible gastropods from north Patagonian harbor areas.
AB  - PAHs are persistent pollutants released into the environment by fossil fuels
      burning and leak during petroleum operations. Associated with suspended particles
      upon entering marine ecosystem are accumulated by benthic fauna. Human exposure
      occurs mainly from ingestion such as gastropods consumption. The objective was to
      determine PAHs in sediments and in the marine gastropod Buccinanops globulosus in
      sites with different maritime and urban influences. In sampling sites located 20
      km from the harbor, PAHs were non-detected; while in harbor gastropods, the level
      of PAH4 was exceeded according to international normative. Level of
      dibenzo[a,h]anthracene in sediments was between the ISQG and PEL. Since these are
      the first results of PAHs in edible gastropods in South America, we concluded
      that PAHs can be dangerous for consumers according to ingestion frequency.
      Integrative studies are necessary to evaluate the interaction among pollutants in
      maritime areas and the incidence in human health due to shellfish consumption.

PMID- 30301104
TI  - Microplastics disturb the anthozoan-algae symbiotic relationship.
AB  - World production of plastic has dramatically increased from the 1950's and now it
      reaches approximately 311 million tons per year. The resulting accumulation of
      small plastic detritus less than 5 mm in size, termed "microplastics", has
      started threatening the life cycles of marine organisms. Here we show the first
      evidence that microplastics disturb the initiation of symbiotic relationships in
      anthozoan-algae symbiosis. We found in both the aposymbiotic sea-anemone Aiptasia
      sp. and the coral Favites chinensis that the infectivity of symbiotic algae into
      the host is severely suppressed by microspheres fed either directly or indirectly
      through microsphere-fed Artemia sp. Similar trends were seen when microplastics
      collected from commercial facewash were used instead of microspheres. Therefore,
      ongoing accumulation of microplastics in the ocean might disturb the healthy
      anthozoan-algae symbiotic relationships, which are cornerstones of the
      biologically enriched coral reef ecosystem.

PMID- 30301105
TI  - Environmental changes in Ariake Sea of Japan and their relationships with Isahaya
      Bay reclamation.
AB  - This paper reviews the recent environmental deterioration in Ariake Sea, Japan,
      including an increased frequency of red tides and hypoxic waters and decreased
      fishery production. Analysis of the mechanisms of environmental deterioration
      suggests that it is possibly induced by the decrease in tidal flat area,
      decreases in the tide and tidal current and changes in the sediment environment.
      The Isahaya Bay reclamation project resulted in the loss of 1550 ha of tidal
      flats, and is one of the possible reasons for the decreases in the tide and tidal
      current. Therefore, some fishermen and researchers believe that opening the
      reclamation project dike's floodgates is an effective environmental restoration
      countermeasure for Ariake Sea. However, the central government decided not to
      open the floodgates at present due to strong opposition from local farmers, and
      some researchers believe that the influences of the Isahaya Bay reclamation
      project on the environmental changes outside of Isahaya Bay are minor. Several
      lawsuits regarding these relationships and the opening of the dike's floodgates
      are currently under dispute. To revive Ariake Sea as a sustainable ecosystem,
      other countermeasures for environmental restoration are suggested and discussed
      in this paper.

PMID- 30301106
TI  - Dumping to the abyss: single-use marine litter invading bathyal plains of the
      Sardinian margin (Tyrrhenian Sea).
AB  - This study reports data on benthic litter abundance, composition and distribution
      obtained during deep-sea trawl surveys conducted along the Sardinian continental
      margin down to the bathyal plain, at depths comprised from 740 to 1740 m. None of
      the investigated sites was litter free. Density ranged from a minimum of 4 to a
      maximum of >1300 litter items per km2, with a mean value of 258 +/- 59 items.
      Plastic accounted for 56% of the total collected items, followed by glass (24%),
      metal (10%). Most items, irrespectively of the category, were single-use items.
      Fish abundance in all of the investigated catches was significantly higher than
      the number of litter items, the weight of which was similar to the reared fish
      biomass. Our results confirm that anthropogenic waste has reached the deep
      Mediterranean Sea, and that the most recent EU legislation banning single-use
      plastic tools represents a timely and necessary measure.

PMID- 30301107
TI  - Seabirds and plastics don't mix: Examining the differences in marine plastic
      ingestion in wedge-tailed shearwater chicks at near-shore and offshore locations.
AB  - Plastic ingestion by wedge-tailed shearwaters (WTS) nesting at near-shore and
      offshore sites along the east coast of Australia were investigated. Ingestion
      rates were at 20% in near-shore lavaged WTS, where the beaches were significantly
      more polluted, compared to 8% in birds at offshore sites. The material and colour
      of recovered plastics at offshore sites differed significantly between beach
      surveys and that ingested by seabirds in the same area. This pattern was not
      evident near-shore. Hence, in near-shore environments birds may feed locally and
      are influenced by nearby plastics, compared to birds offshore. The origins of
      marine debris between near-shore and offshore beaches differed; with land-based
      sources unsurprisingly having more influence on near-shore sites. The findings of
      this study indicate the need for localised data to address and manage this
      pollutant, with nesting seabirds at greater risk in near-shore environments. A
      preliminary modified ecological quality objective for WTS is presented.

PMID- 30301108
TI  - Type and quantity of coastal debris pollution in Taiwan: A 12-year nationwide
      assessment using citizen science data.
AB  - Man-made coastal debris pollution is a growing concern for Taiwan. In 2004,
      Taiwanese environmental organizations led by the "Society of Wilderness" began
      gathering data on 19 categories of debris items collected during cleanup events.
      We present our analysis of the resulting 12-year dataset collated from 541 events
      held between October 2004 and December 2016. In total, 904,302 items weighing
      131,358.3 kg were collected, and 63.6% and 27.2% of items were made of either
      plastic or plastic mixed with other materials, respectively. The five most
      commonly recorded debris categories were plastic shopping bags, plastic bottle
      caps, disposable tablewares, fishing equipment, and plastic drinking straws. We
      estimated that during the 12-year period on average between 3.7 and 7.9 million
      items weighing 560-1110 metric tons polluted Taiwan's coastline. We offer
      recommendations for improving the quality of data collected during Taiwan's
      cleanup events and report some policy changes due partly to previous reports of
      this dataset.

PMID- 30301109
TI  - Thyasira tokunagai as an ecological indicator for the quality of sediment and
      benthic communities in the East Sea-Byeong, Korea.
AB  - The biomass and abundance of molluscan species were identified to evaluate the
      ecological quality of the surface sediment at the East Sea-Byeong ocean dumping
      site, Korea. To identify the dominant molluscan species, sediment samples were
      collected at nine selected stations during five expeditions in 2009, 2012, 2013,
      2014, and 2015. In total, 16 molluscan species, including Aplacophora,
      Gastropoda, Bivalvia, and Scaphopoda, were observed. The bivalve Thyasira
      tokunagai was the dominant species, accounting for 82.6% of the total abundance
      of all identified species. This species was also the dominant benthic molluscan
      in sediments rich in organic matter and with a low manganese content. In
      addition, environmental variables, including sediment grain size, water depth,
      total organic carbon, and heavy metals, were found to be critical drivers
      affecting the spatial distribution of molluscan species.

PMID- 30301110
TI  - Temporal metal concentration in coastal sediment at the north region of Persian
      Gulf.
AB  - The purpose of this article is to study, result of metal concentration in two
      sediment cores from Persian Gulf. Age of sediment is determined by C14 isotope
      method and bulk concentration is determined by ICP. This research output shows
      that, age of BandareAbbas core back to 9660 and Bushehr core to 15,600 years ago.
      Also,concentration in BandareAbbas and Bushehr cores respectively change as, As
      (1.08-11.76 Vs 5.2-13.09), Ba (15.03-129.5 Vs 73.9-120.4), Cd (0.09-0.46 Vs 0.09
      0.18), Li (5.66-58.5 Vs 15.3-33.4), Mo (0.3-0.75 Vs 0.3-0.8), Mg (7928.4-15,503.9
      Vs 13,102.8-17,227.8), Mn (110.6-566.4 Vs 279.3-429.1), Na (8905.47-27,993.3 Vs
      9357.7-27,541.4), Ni (13.3-110.3 Vs 37.1-88.4), Pb (0.5-42.5 Vs 2.5-13.6), Sr
      (407.5-1773.2 Vs 440.3-1596.9), Zn (13.05-71.2Vs22.4-50.5), Fe (0.46-4.07 Vs 1.7
      3.18), Ca (9.25-23.3 Vs 13.8-19.2) and Al (0.62-8.15 Vs 2.48-4.65). Moreover
      different pollution index investigation represent that except Ca, the rest of the
      metal elements do not show pollution.

PMID- 30301111
TI  - Occurrence of microplastics in fishes from two landing sites in Tuticorin, South
      east coast of India.
AB  - Microplastics pollution of the marine environment has been reported worldwide.
      Here, we investigate the occurrence of microplastics in two species of fishes
      namely Rastrilleger kanagurta and Epinephalus merra bought from Thirespuram and
      Punnakayal fish landing sites at Tuticorin. Out of the total 40 fish, 12 fish
      showed the presence of microplastic particulates in the intestine. The
      particulates included microfibers (80%) in red, black and translucent colors and
      irregularly shaped microplastic fragments (20%). The microplastics were
      identified as Polyethylene and Polypropylene by Fourier Transform Infrared
      Radiation analysis. Though microplastics were detected in the gut of the species,
      the risk of transfer due to consumption can be safely ruled out as the fish are
      degutted prior to consumption here. Presence of microplastics in the Tuticorin
      coast is a matter of concern due to its proximity to the Gulf of Mannar, a
      sensitive coral reef patch already threatened by marine pollution.

PMID- 30301112
TI  - Similarities and differences of 137Cs distributions in the marine environments of
      the Baltic and Black seas and off the Fukushima Dai-ichi nuclear power plant in
      model assessments.
AB  - The compartment model POSEIDON-R with an embedded food web model was used to
      assess 137Cs distributions in the Baltic and Black seas and off the Pacific coast
      of Japan during 1945-2020 due to the weapon testing and accidents at the
      Chernobyl and Fukushima Dai-ichi nuclear power plants. The results of simulations
      conducted with generic parameters agreed well with measurements of 137Cs
      concentrations in the water, bottom sediments, and in fish. In the Black and
      Baltic seas, salinity variations affected the transfer of 137Cs through the food
      web. The contamination of pelagic fish followed the water contamination with some
      delay, whereas demersal fish depuration was found to be related to decreasing
      137Cs concentrations in the upper sediment layer. On the Pacific shelf off Japan,
      intensive currents and eddies caused the simulated depuration rates in fish to be
      one-two orders of magnitude larger than those in the semi-enclosed Black and
      Baltic seas.

PMID- 30301113
TI  - Trace metal concentrations in the muscle of seven marine species: Comparison
      between the Gulf of Lions (North-West Mediterranean Sea) and the Bay of Biscay
      (North-East Atlantic Ocean).
AB  - Concentrations of 6 trace metals (Ag, Cd, Cu, Ni, Pb, Zn) in the muscle of 2
      sharks (Galeus melastomus and Scyliorhinus canicula), 4 teleosts (Helicolenus
      dactylopterus, Lepidorhombus boscii, Micromesistius poutassou and Phycis
      blennoides) and 1 crustacean (Nephrops norvegicus) were compared between the Bay
      of Biscay (Atlantic Ocean) and the Gulf of Lions (Mediterranean Sea). Although
      average concentrations and the trace element pollution index were generally
      higher in the Gulf of Lions, significant differences between the two ecosystems
      were only found for Zn for Helicolenus dactylopterus, and for Ag and Cu for the
      crustacean N. norvegicus. Moreover, some relationships between trophic level or
      size and metal concentrations were found for these two species. The absence of
      clear pattern may result from the blurring effect of contamination and excretion
      that may act differentially for all species and all elements.

PMID- 30301114
TI  - Distribution, composition, and ecological risk of surface sedimental
      polychlorinated naphthalenes in the East China Sea.
AB  - To reveal the pollution levels and estimate the ecological risks of
      polychlorinated naphthalenes (PCNs) in the East China Sea (ECS), seventy-five
      surface sediment samples were collected and analyzed by high-resolution mass
      spectrometry. PCN contents ranged from below detection limit to 261.71 ng/g dry
      weight (d.w.), with an integrally seaward decreasing trend. Mono-, tetra-, and
      hepta-CNs were the dominant homologs, and CN-2, CN-73, and CN-75 were the major
      individual components in most samples. CN-2 presented an obvious boundary with
      lower contents (16.48 +/- 3.40 ng/g d.w.) in the center of the study area and
      higher contents (50.88 +/- 10.39 ng/g d.w.) in the north and south of the
      boundary. The toxic equivalent (TEQ) contents ranged from 0 to 0.212 ng/g, and CN
      2 and CN-73 were the predominant contributors to the TEQ.

PMID- 30301115
TI  - Nitrogen and sulfur isotopes predict variation in mercury levels in Arctic
      seabird prey.
AB  - Mercury (Hg) biotransformation and biomagnification are processes that affect Hg
      burdens in wildlife. To interpret variation in Hg in seabird eggs, used as Hg
      bioindicators in the Arctic, it is important to understand how Hg biomagnifies
      through the food web. We evaluated the use of delta34S, along with other commonly
      used stable isotope signatures (delta15N and delta13C), for the determination of
      possible sources of Hg in an Arctic food web (56 individuals of 15 species of
      fish and invertebrates). Hg correlated with delta34S (R2 = 0.72). When the
      combined effects of delta34S and delta15N were considered in mixed-effects
      models, both delta34S and delta15N together described Hg patterns in Arctic food
      webs better than either isotope alone. Our results demonstrate the usefulness of
      delta34S to account for variation in Hg among marine animals and to study the
      possible underlying effects that MeHg production may have on Hg pathways in
      Arctic ecosystems.

PMID- 30301116
TI  - Risk assessment of oil spills in the Chinese Bohai Sea for prevention and
      readiness.
AB  - Oil spill accidents occur with increasing frequency in the Chinese Bohai Sea
      because of the presence of extensive number of oil platforms and oil pipelines
      the Chinese Bohai region. An appropriate risk assessment for oil spill prevention
      and readiness is necessary. Risk assessment for the entire Chinese Bohai Sea
      based on a quantitative method is proposed. We created a hypothetical simulation
      of oil spill trajectories based on an oil spill model for 28 oil platforms in the
      Chinese Bohai region in 2010. Then, we mapped a risk index in the study areas
      based on a combination of oil spill trajectories and shoreline susceptibility
      data. Five high-risk areas were identified in the entire Chinese Bohai Sea.
      Detailed suggestions for prevention and readiness are described here. These
      results can help in developing a risk assessment of oil spills in the Chinese
      Bohai Sea and serve as a useful analytic tool for slick-related emergencies.

PMID- 30301117
TI  - Background levels of trace elements in brown and red seaweeds from Trindade, a
      remote island in South Atlantic Ocean.
AB  - Trace elements in organisms are normally higher in well-developed coastal areas
      than on oceanic islands. Few studies have used seaweeds as their sentinels on
      islands. This study established background levels of trace elements (As, Cd, Pb,
      Zn, Cu and Hg) for four seaweed species (Dictyopteris delicatula and
      Canistrocarpus cervicornis, brown algae; Ceratodictyon variabile and Palisada
      perforata, red algae) from Trindade, an oceanic Brazilian island, and verified
      potential differences associated to distinct environmental conditions. Spatial
      differences were not detected for As, Hg and Cd in samples, although the highest
      concentrations of these elements were observed in brown seaweeds. The highest Zn,
      Pb and Cu concentrations in seaweeds from the only inhabited beach may be a
      signal of the onset of human footprints on this still pristine, remote island. By
      comparison with background described in the literature, concentrations of trace
      elements in seaweeds were low, thus, allowing them to be considered reference
      levels.

PMID- 30301118
TI  - Microplastics in Galway Bay: A comparison of sampling and separation methods.
AB  - Microplastics, an emerging pollutant, are recognised as having a ubiquitous
      distribution in the environment. Currently several benthic sampling tools are
      being employed to collect subtidal marine sediment, however, there are no
      comparative studies on the efficiency of these tools to sample for microplastics
      or the subsequent extraction methods of microplastics from these marine
      sediments. This study addresses these knowledge gaps by comparing commonly
      applied benthic sampling tools (Van Veen grab, box corer, gravity corer) and a
      variety of density separation methods (elutriation column, sodium chloride
      solution, sodium tungstate dihydrate solution) for microplastic collection and
      processing. Each sampling tool was tested at the same station and the collected
      sediment was used to assess the extraction performance for the different density
      separation techniques. No statistically significant differences were found
      between the concentrations of microplastics extracted for any of the sampling
      tools. However, there were significant differences between the density separation
      methods using sodium tungstate dihydrate and sodium chloride solution and the
      elutriation method. This preliminary study provides evidence that the sampling
      tools tested are both suitable and proficient at determining the abundance of
      microplastics in sediments. Sodium tungstate dihydrate proved to be a novel and
      feasible option for dense liquid separation of microplastics in subtidal marine
      sediments. These results will allow for more confidence in data quality when
      comparing future surveys applying different benthic sampling tools.

PMID- 30301119
TI  - Sediment characteristics influence the fertilisation success of the corals
      Acropora tenuis and Acropora millepora.
AB  - Elevated suspended sediment concentrations (SSCs) often impact coral
      fertilisation success, but sediment composition can influence effect thresholds,
      which is problematic for accurately predicting risk. Here, we derived
      concentration-response thresholds and cause-effect pathways for SSCs comprising a
      range of realistic mineral and organic compositions on coral fertilisation
      success. Effect concentration thresholds (EC10: 10% fertilisation inhibition)
      varied markedly, with fertilisation highly sensitive to inshore organic-clay rich
      sediments and bentonite clay at <5 mg L-1. Mineral clays and organic matter
      within these sediments likely promoted flocculation of the coral sperm, which in
      turn reduced fertilisation. In contrast, sediments lacking these properties bound
      less sperm, leading to higher SSC thresholds for coral fertilisation (EC10 > 40
      mg L-1). The effect thresholds for relevant sediment types were combined with in
      situ turbidity data from locations near dredging operations to assess the risks
      posed by dredging to coral fertilisation at these locations.

PMID- 30301120
TI  - Macrobenthic community characteristics and ecological health of a constructed
      intertidal oyster reef in the Yangtze Estuary, China.
AB  - Development of substrate organisms (oysters, barnacles) and the health of a
      monitored oyster reef were investigated in the Yangtze Estuary. Very low salinity
      suppressed oyster survival. Nevertheless, middle- to high-salinity significantly
      increased the abundance and biomass of substrate organisms, and macrobenthos
      species and diversity. Long-term variation in substrate organisms was steady
      after a major fluctuation, yet the macrobenthic community structure lagged behind
      that of oysters. Overall, the oyster reef was in a healthy state. The M-AMBI
      results showed that its ecological status under high-salinity was better than
      medium-salinity conditions. Redundancy analysis indicated these results were
      associated with changes in water salinity and substrate factors. Taken together,
      our results suggest this constructed intertidal oyster reef has had a positive
      effect on the community and health status of macrobenthos in the Yangtze Estuary.
      Further, these ecological benefits increased going from medium- to high-salinity
      waters, but were generally absent under low salinity.

PMID- 30301121
TI  - Simulated fate of catchment-derived sediment on the Great Barrier Reef shelf.
AB  - Numerical experiments using a 3D model of fine sediment transport in the Great
      Barrier Reef region indicate deposition of the bulk mass of catchment sediments
      from river plumes within a few tens of kilometres from river mouths. A very fine
      fraction of easily resuspended catchment sediment has a capacity to propagate
      over much greater distances reaching out into the mid-shelf and outer-shelf
      regions. The model suggests such particles, instrumental to the development of
      low density flocs in the marine environment, can play a critical role in altering
      optical properties of water masses over the shelf during wet years. The mid-term
      (4 year) impact of Great Barrier Reef catchments on the probability of suspended
      sediment concentration exceeding the ecologically significant trigger value of 2
      mg/L is confined to inshore regions adjacent to river mouth locations.

PMID- 30301122
TI  - An online platform for rapid oil outflow assessment from grounded tankers for
      pollution response.
AB  - The risk of oil spills is an ongoing societal concern. Whereas several decision
      support systems exist for predicting the fate and drift of spilled oil, there is
      a lack of accurate models for assessing the amount of oil spilled and its
      temporal evolution. In order to close this gap, this paper presents an online
      platform for the fast assessment of tanker grounding accidents in terms of
      structural damage and time-dependent amount of spilled cargo oil. The simulation
      platform consists of the definition of accidental scenarios; the assessment of
      the grounding damage and the prediction of the time-dependent oil spill size. The
      performance of this integrated online simulation environment is exemplified
      through illustrative case studies representing two plausible accidental grounding
      scenarios in the Gulf of Finland: one resulting in oil spill of about 50 t, while
      in the other the inner hull remained intact and no spill occurred.

PMID- 30301123
TI  - Environmental regeneration processes in the Anthropocene: The Bilbao estuary case
      (northern Spain).
AB  - This work tackles a multidisciplinary study on the recent sedimentary record of
      the Bilbao estuary (northern Spain), which is the backbone of a city that was
      primarily industrial and now is widely recognized as a successful example of
      urban transformation. Although hotspots of heavily polluted materials still
      remain at the mouth of the two main tributaries (Galindo and Gobelas), the data
      obtained confirm the ongoing formation of a new layer of sediments (here called
      "postindustrial zone") covering historically polluted and azoic deposits. It is
      characterized by largely variable levels of metals and magnetic susceptibility
      and moderate-to-high abundances of benthic foraminifera. Monitoring of the
      evolution of this layer appears a key factor to assess environmental improvement
      and decision-making in polluted estuaries.

PMID- 30301124
TI  - Biomonitoring coastal environments with transplanted macroalgae: A methodological
      review.
AB  - The use of macroalgae transplants is a recent technique used in pollution
      biomonitoring studies in marine ecosystems. Only 60 articles published between
      1978 and 2017 reported the use of this environmental tool for the active
      biomonitoring of inorganic pollutants and nutrients worldwide. In this review
      paper, we evaluated studies on this topic in relation to the development of
      methodological aspects of the technique and the degree of standardization of the
      protocols used. On the basis of findings of this review, we conclude that the
      technique is not yet standardized and that uniformisation of protocols is
      required to enable comparison of the results of different studies. We propose a
      new protocol for applying the technique, in which each suggestion has been
      carefully and rigorously compared with the relevant findings reported in the
      available literature.

PMID- 30301125
TI  - Non-Human Primate Models of Enteric Viral Infections.
AB  - There is an important role non-human primates (NHP) play in biomedical research.
      Phylogenetic proximity of any of the NHP species to Homo sapiens assures that
      much better translatability of research outcomes from model studies involving
      human diseases can be achieved than from those generated with other pre-clinical
      systems. Our group and others used during past two decades NHPs in research
      directed towards viral and autoimmune disorders of the gastrointestinal tract.
      This review summarizes progress made in the area of enteric viral infections
      including its applicability to human disease.

PMID- 30301126
TI  - The Effect of Extensive Human Presence at an Early Age on Stress Responses and
      Reactivity of Juvenile Ostriches towards Humans.
AB  - The effect of extensive human presence and regular gentle handling performed at
      an early age (0-3 months old) on stress responses and reactivity of juvenile
      ostriches towards humans was investigated. A total of 416 ostrich chicks over two
      years were exposed to one of three treatments for three months after hatching;
      namely, Human Presence 1 (HP1, N = 144): extensive/prolonged human presence with
      physical contact (touch, stroking), gentle human voice, and visual stimuli; Human
      Presence 2 (HP2, N = 136): extensive/prolonged human presence without physical
      contact, but with gentle human voice and visual stimuli; and the Standard
      treatment (S, N = 136): human presence limited to routine feed and water supply
      as a control. At 7.5 months of age, the plasma heterophil/lymphocyte (H/L) ratio
      was measured before and 72 h after feather harvesting and feather clipping to
      determine acute stress responses, while chronic stress was measured by
      quantification of corticosterone (CORT) concentrations in the floss feathers of
      the birds. Birds' behavioural response towards a familiar or an unfamiliar
      handler was evaluated at 12 months using docility and fear tests, and through
      behavioural observations conducted on random days between the ages of 8-13
      months. Willingness to approach, and to allow touch interactions, aggressiveness,
      and exhibition of sexual display towards the handler, was recorded. No difference
      in the H/L ratios before and after feather harvesting and clipping was observed
      in HP1 birds, whereas H/L ratios showed a significant increase 72 h post feather
      harvesting and clipping in HP2 and S birds (p < 0.05). Birds from the S treatment
      exhibited a significantly (p < 0.05) higher feather CORT concentration compared
      with HP1 birds, while HP2 birds had intermediate responses. Birds' reactivity
      towards humans and temperament as evaluated using behavioural observations,
      docility, and fear tests was not affected by treatment (p > 0.05). However, HP1
      and HP2 birds were more inclined (p < 0.05) to approach a familiar rather than an
      unfamiliar handler during the behavioural observations, indicating an ability to
      distinguish between a familiar and an unfamiliar handler. Overall, the results
      indicate that early gentle human interactions with ostrich chicks can be
      beneficial in reducing physiological stress sensitivity later in life and
      facilitate the ability of ostriches to distinguish between familiar and
      unfamiliar handlers.

PMID- 30301127
TI  - Regular Intake of a Usual Serving Size of Flavanol-Rich Cocoa Powder Does Not
      Affect Cardiometabolic Parameters in Stably Treated Patients with Type 2 Diabetes
      and Hypertension-A Double-Blinded, Randomized, Placebo-Controlled Trial.
AB  - Regular cocoa consumption has been shown to improve blood pressure (BP), insulin
      sensitivity, and lipid levels in patients with type 2 diabetes (T2D), using up to
      100 g of chocolate or 54 g of cocoa. These effects, attributed to cocoa
      flavanols, would be beneficial for patients with T2D if they could be achieved by
      a usual serving size of flavanol-rich cocoa. Forty-two hypertensive patients with
      T2D (stable pharmacological treatment, with good adjustment for glucose
      metabolism, lipids, and BP) ingested capsules with 2.5 g/day of a flavanol-rich
      cocoa or cocoa-free capsules for 12 weeks in a double-blinded, randomized,
      placebo-controlled study with parallel group design. Participants had to maintain
      diet, lifestyle, and medication. Before and after intervention, fasting blood
      samples were collected; BP and nutritional status were investigated. Cocoa
      treatment did not affect BP, nor glucose metabolism (glucose, HbA1c, insulin,
      HOMA-IR) and lipids (triglycerides, total cholesterol, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol). Body weight, fat mass, and
      nutrient supply remained unchanged. Changes in the placebo group did not occur.
      Regular intake of a usual serving size of flavanol-rich cocoa does not improve
      cardiometabolic parameters in stably treated patients with T2D and hypertension.
      As the medication modulates partly the same targets as cocoa flavanols, future
      studies should focus on the preventive effect of cocoa against diabetes and other
      cardiometabolic diseases in individuals with preexisting abnormalities that do
      not require any pharmacological treatment.

PMID- 30301128
TI  - Maternal Protein Restriction Alters the Renal Ptger1 DNA Methylation State in
      SHRSP Offspring.
AB  - We previously reported that maternal protein restriction (LP) during pregnancy
      increases salt sensitivity in offspring using the Stroke-Prone Spontaneously
      Hypertensive Rat (SHRSP). In the present study, we focus on DNA methylation
      profiles of prostaglandin E receptor 1 gene (ptger1), which is known to be
      associated with hypertension. We evaluated the ptger1 DNA methylation status via
      bisulfite sequencing, and analyzed the expression of ptger1-related genes. The
      results of these analyses showed that, compared to controls, the LP-S offspring
      exhibited both marked ptger1 hypermethylation, and significantly increased ptger1
      expression. Moreover, they also exhibited significantly decreased expression of
      the downstream gene epithelial Na+ channel alpha (enacalpha). Interestingly, LP
      offspring that were provided with a standard water drinking supply (W) also
      exhibited increased ptger1 methylation and expression. Together, these results
      suggest that maternal protein restriction during pregnancy modulates the renal
      ptger1 DNA methylation state in SHRSP offspring, and thereby likely mediates
      ptger1 and enacalpha gene expression to induce salt sensitivity.

PMID- 30301129
TI  - Ironing out the Details: Untangling Dietary Iron and Genetic Background in
      Diabetes.
AB  - The search for genetic risk factors in type-II diabetes has been hindered by a
      failure to consider dietary variables. Dietary nutrients impact metabolic disease
      risk and severity and are essential to maintaining metabolic health. Genetic
      variation between individuals confers differences in metabolism, which directly
      impacts response to diet. Most studies attempting to identify genetic risk
      factors in disease fail to incorporate dietary components, and thus are ill
      equipped to capture the breadth of the genome's impact on metabolism.
      Understanding how genetic background interacts with nutrients holds the key to
      predicting and preventing metabolic diseases through the implementation of
      personalized nutrition. Dysregulation of iron homeostasis is associated with type
      II diabetes, but the link between dietary iron and metabolic dysfunction is
      poorly defined. High iron burden in adipose tissue induces insulin resistance,
      but the mechanisms underlying adipose iron accumulation remain unknown. Hepcidin
      controls dietary iron absorption and distribution in metabolic tissues, but it is
      unknown whether genetic variation influencing hepcidin expression modifies
      susceptibility to dietary iron-induced insulin resistance. This review highlights
      discoveries concerning the axis of iron homeostasis and adipose function and
      suggests that genetic variation underlying dietary iron metabolism is an
      understudied component of metabolic disease.

PMID- 30301130
TI  - Zinc Content in Breast Milk and Its Association with Maternal Diet.
AB  - BACKGROUND: Zinc is an indispensable element, being involved in many biological
      processes. Correspondingly, insufficient zinc intake in early youth can
      detrimentally affect the function of a growing body. The aim of this study was to
      determine zinc content in breast milk among lactating women in Latvia and factors
      (maternal diet; mother's and baby's characteristics; breastfeeding pattern)
      affecting it. METHODS: In total, 62 mature milk (at least one month postpartum)
      samples were collected and pooled within 24 h. Zinc content (mg 100 mL-1) was
      determined using inductively coupled plasma mass spectrometry (ICP-MS; Agilent
      7700*, Agilent Technologies, Tokyo, Japan). RESULTS: Zinc content in mature
      breast milk ranged from 0.01 to 0.34 mg 100 mL-1 with a median (interquartile
      range) content of 0.10 (0.05-0.15) mg 100 mL-1. Time postpartum was a significant
      negative predictor for zinc content in breast milk (r = -0.500; p = 0.000).
      Median maternal zinc intake was 10.70 (7.24-15.27) mg. Yet, zinc content in
      breast milk was unaffected by maternal dietary zinc intake (r = 0.155; p =
      0.221). CONCLUSIONS: Maternal dietary zinc intake was nearly the recommended
      intake for lactating women (11 mg), but due to low zinc content in breast milk,
      babies in Latvia might not receive sufficient zinc intake. Future research should
      aim for the assessment of zinc status by evaluating plasma or serum levels of
      both mothers and babies.

PMID- 30301131
TI  - Are Clean Eating Blogs a Source of Healthy Recipes? A Comparative Study of the
      Nutrient Composition of Foods with and without Clean Eating Claims.
AB  - Food blogs are an increasingly popular source of information about food and
      nutrition. There is a perception that foods published on clean eating blogs,
      which promote unprocessed foods, are healthier than comparable foods without
      these claims. However, foods with these claims and their nutrient composition
      have not previously been evaluated. The purpose of the study was to describe the
      nutritional content of clean eating recipes compared to recipes without clean
      eating claims and the nutritional guidelines published by the World Health
      Organisation (WHO). Clean eating recipes were systematically selected from 13
      popular clean eating blogs and were described and compared with control recipes
      without clean eating claims. The nutrient profiles from the included recipes were
      summarised and evaluated against criteria from WHO recommendations for chronic
      disease prevention and criteria from the U.K. Food Standards Agency. Data for 86
      clean eating recipes were extracted that represented five food categories:
      breakfast, snacks, treats, desserts, and smoothies. These were matched with 86
      control recipes without clean eating claims. The clean eating recipes, per
      portion, provide the equivalent of 15% of daily energy intake. The average
      serving sizes were not significantly different between clean eating and control
      recipes. Overall, the clean eating recipes contained significantly more protein
      (8.1 +/- 7.3 g vs. 5.7 +/- 4.1 g, p = 0.01), fat (15.8 +/- 10.6 g vs. 12.4 +/-
      9.3 g, p = 0.03), and fibre (5.0 +/- 4.3 g vs. 2.8 +/- 2.9 g, p < 0.01) per
      serving than control recipes. There were no significant differences between clean
      eating and control recipes with respect to the energy (1280 +/- 714 kJ vs. 1137
      +/- 600 kJ, p = 0.16), carbohydrate (31.5 +/- 27.3 g vs. 33.9 +/- 19.4 g, p =
      0.51), sugar (21.1 +/- 20.9 g vs. 23.2 +/- 14.9 g, p = 0.46), and sodium content
      (196.7 +/- 269 vs. 155.8 +/- 160.8, p = 0.23). Less than 10% of clean eating and
      control recipes met the WHO constraints for proportions of energy from fat and
      sugar intake. A simulated nutrient profile of an average clean and control recipe
      shows that nutrients for both are similarly classified as moderate to high in
      fat, saturated fat, salt, and sugar. Foods with clean eating claims contained the
      same amount of energy, sugar, and sodium as foods without those claims. Clean
      eating claims are potentially misleading for consumers who may believe these
      foods are healthy alternatives, potentially undermining people's efforts to eat a
      healthy diet.

PMID- 30301133
TI  - Filling of Irregular Channels with Round Cross-Section: Modeling Aspects to Study
      the Properties of Porous Materials.
AB  - The filling of channels in porous media with particles of a material can be
      interpreted in a first approximation as a packing of spheres in cylindrical
      recipients. Numerous studies on micro- and nanoscopic scales show that they are,
      as a rule, not ideal cylinders. In this paper, the channels, which have an
      irregular shape and a circular cross-section, as well as the packing algorithms
      are investigated. Five patterns of channel shapes are detected to represent any
      irregular porous structures. A novel heuristic packing algorithm for monosized
      spheres and different irregularities is proposed. It begins with an initial
      configuration based on an fcc unit cell and the subsequent densification of the
      obtained structure by shaking and gravity procedures. A verification of the
      algorithm was carried out for nine sinusoidal axisymmetric channels with
      different Dmin/Dmax ratio by MATLAB(r) simulations, reaching a packing fraction
      of at least 0.67 (for sphere diameters of 5%Dmin or less), superior to a random
      close packing density. The maximum packing fraction was 73.01% for a channel with
      a ratio of Dmin/Dmax = 0.1 and a sphere size of 5%Dmin. For sphere diameters of
      50%Dmin or larger, it was possible to increase the packing factor after applying
      shaking and gravity movements.

PMID- 30301132
TI  - The Gliocentric Brain.
AB  - The Neuron Doctrine, the cornerstone of research on normal and abnormal brain
      functions for over a century, has failed to discern the basis of complex
      cognitive functions. The location and mechanisms of memory storage and recall,
      consciousness, and learning, remain enigmatic. The purpose of this article is to
      critically review the Neuron Doctrine in light of empirical data over the past
      three decades. Similarly, the central role of the synapse and associated neural
      networks, as well as ancillary hypotheses, such as gamma synchrony and cortical
      minicolumns, are critically examined. It is concluded that each is fundamentally
      flawed and that, over the past three decades, the study of non-neuronal cells,
      particularly astrocytes, has shown that virtually all functions ascribed to
      neurons are largely the result of direct or indirect actions of glia continuously
      interacting with neurons and neural networks. Recognition of non-neural cells in
      higher brain functions is extremely important. The strict adherence of purely
      neurocentric ideas, deeply ingrained in the great majority of neuroscientists,
      remains a detriment to understanding normal and abnormal brain functions. By
      broadening brain information processing beyond neurons, progress in understanding
      higher level brain functions, as well as neurodegenerative and neurodevelopmental
      disorders, will progress beyond the impasse that has been evident for decades.

PMID- 30301134
TI  - Differential Effect of Cobalt and Chromium Ions as Well as CoCr Particles on the
      Expression of Osteogenic Markers and Osteoblast Function.
AB  - The balance of bone formation and resorption is the result of a regulated
      crosstalk between osteoblasts, osteoclasts, and osteocytes. Inflammation,
      mechanical load, and external stimuli modulate this system. Exposure of bone
      cells to metal ions or wear particles are thought to cause osteolysis via
      activation of osteoclasts and inhibition of osteoblast activity. Co2+ ions have
      been shown to impair osteoblast function and the expression of the three
      transforming growth factor (TGF)-beta isoforms. The current study was performed
      to analyze how Co2+ and Cr3+ influence the expression, proliferation, and
      migration profile of osteoblast-like cells. The influence of Co2+, Cr3+, and CoCr
      particles on gene expression was analyzed using an osteogenesis PCR Array. The
      expression of different members of the TGF-beta signaling cascade were down
      regulated by Co2+, as well as several TGF-beta regulated collagens, however, Cr3+
      had no effect. CoCr particles partially affected similar genes as the
      Co2+treatment. Total collagen production of Co2+ treated osteoblasts was reduced,
      which can be explained by the reduced expression levels of various collagens.
      While proliferation of MG63 cells appears unaffected by Co2+, the migration
      capacity was impaired. Our data may improve the knowledge of changes in gene
      expression patterns, and the proliferation and migration effects caused by
      artificial materials.

PMID- 30301135
TI  - Impact of Rehabilitation on Outcomes after TAVI: A Preliminary Study.
AB  - The benefit of rehabilitation in elderly patients undergoing transcatheter aortic
      valve implantation (TAVI) for treatment of severe aortic stenosis is unknown. The
      impact of declining rehabilitation programs on mortality has also not been
      described. In a longitudinal cohort study of 1056 patients undergoing elective
      TAVI between 2008 and 2016, logistic regression analysis was used to assess the
      relationship between treatment modality and outcome according to whether or not
      patients participated in a three-week rehabilitation program after TAVI. Subgroup
      analyses included patient outcome separated according to cardiac, geriatric, or
      no rehabilitation. A total of 1017 patients survived until hospital discharge
      (96.3%) and were offered rehabilitation, 366 patients (36.0%) declined to undergo
      rehabilitation, with the remaining patients undergoing either cardiac (n = 435;
      42.8%) or geriatric rehabilitation (n = 216; 21.2%). Mortality at six months was
      lower for patients receiving rehabilitation compared with those who had not
      (adjusted odds ratio (OR): 0.49; 95% confidence interval (confidence interval
      [CI]: 0.25-0.94; p = 0.032). Sub-analysis showed the benefit of cardiac (adjusted
      OR: 0.31; 95% CI 0.14-0.71, p = 0.006), but not geriatric rehabilitation
      (adjusted OR 0.83; 95% CI 0.37-1.85, p = 0.65). A program of rehabilitation after
      TAVI has the potential to reduce mortality. Future studies should focus on health
      orientated behavior and identifying risk factors for declining rehabilitation
      programs.

PMID- 30301136
TI  - Paired CRISPR/Cas9 Nickases Mediate Efficient Site-Specific Integration of F9
      into rDNA Locus of Mouse ESCs.
AB  - Hemophilia B (HB) is an X-linked recessive bleeding disorder, caused by F9 gene
      deficiency. Gene therapy combined with the CRISPR/Cas9 technology offers a
      potential cure for hemophilia B. Now the Cas9 nickase (Cas9n) shows a great
      advantage in reducing off-target effect compared with wild-type Cas9. In this
      study, we found that in the multicopy ribosomal DNA (rDNA) locus, the homology
      directed recombination (HDR) efficiency induced by sgRNA-Cas9n was much higher
      than sgRNA-Cas9, meanwhile without off-target in six predicted sites. After co
      transfection into mESCs with sgRNA-Cas9n and a non-viral rDNA targeting vector
      pMrnF9, harboring the homology donor template and the human F9 expression
      cassette, a recombination efficiency of 66.7% was achieved and all targeted
      clones were confirmed to be site-specific integration of F9 in the rDNA locus by
      PCR and southern blotting. Targeted mESCs retained the main pluripotent
      properties and were then differentiated into hepatic progenitor like cells
      (HPLCs) and mature hepatocytes, which were characterized by hepatic markers and
      functional assays. Importantly, the differentiated cells could transcribe
      exogenous F9 and secrete coagulation factor IX (FIX) proteins, suggesting active
      transcription and stable inheritance of transgenes in the rDNA locus. After
      intrasplenical transplantation in severe combined immune deficiency (SCID) mice,
      targeted HPLCs could survive and migrate from spleen to liver, resulting in
      secretion of exogenous FIX into blood. In summary, we demonstrate an efficient
      and site-specific gene targeting strategy in rDNA locus for stem cell-based gene
      therapy for hemophilia B.

PMID- 30301138
TI  - Significance of Brownian Motion for Nanoparticle and Virus Capture in
      Nanocellulose-Based Filter Paper.
AB  - Pressure-dependent breakthrough of nanobioparticles in filtration was observed
      and it was related to depend on both convective forces due to flow and diffusion
      as a result of Brownian motion. The aim of this work was to investigate the
      significance of Brownian motion on nanoparticle and virus capture in a
      nanocellulose-based virus removal filter paper through theoretical modeling and
      filtration experiments. Local flow velocities in the pores of the filter paper
      were modeled through two different approaches (i.e., with the Hagen-Poiseuille
      equation) and by evaluating the superficial linear flow velocity through the
      filter. Simulations by solving the Langevin equation for 5 nm gold particles and
      28 nm PhiX174 bacteriophages showed that hydrodynamic constraint is favored for
      larger particles. Filtration of gold nanoparticles showed no difference in
      retention for the investigated fluxes, as predicted by the modeling of local flow
      velocities. Filtration of PhiX174 bacteriophages exhibited a higher retention at
      higher filtration pressure, which was predicted to some extent by the Hagen
      Poiseuille equation but not by evaluation of the superficial linear velocity. In
      all, the hydrodynamic theory was shown able to explain some of the observations
      during filtration.

PMID- 30301137
TI  - Peroxiredoxins in Colorectal Cancer: Predictive Biomarkers of Radiation Response
      and Therapeutic Targets to Increase Radiation Sensitivity?
AB  - Colorectal cancer (CRC) is the third most common cancer in the Western world,
      with one-third of cases located in the rectum. Preoperative radiotherapy is the
      standard of care for many patients with rectal cancer but has a highly variable
      response rate. The ability to predict response would be of great clinical
      utility. The response of cells to ionizing radiation is known to involve
      immediate damage to biomolecules and more sustained disruption of redox
      homeostasis leading to cell death. The peroxiredoxins are an important group of
      thiol-dependent antioxidants involved in protecting cells from oxidative stress
      and regulating signaling pathways involved in cellular responses to oxidative
      stress. All six human peroxiredoxins have shown increased expression in CRC and
      may be associated with clinicopathological features and tumor response to
      ionizing radiation. Peroxiredoxins can act as markers of oxidative stress in
      various biological systems but they have not been investigated in this capacity
      in CRC. As such, there is currently insufficient evidence to support the role of
      peroxiredoxins as clinical biomarkers, but it is an area worthy of investigation.
      Future research should focus on the in vivo response of rectal cancer to
      radiotherapy and the redox status of peroxiredoxins in rectal cancer cells, in
      order to predict response to radiotherapy. The peroxiredoxin system is also a
      potential therapeutic target for CRC.

PMID- 30301140
TI  - Fucosterol from an Edible Brown Alga Ecklonia stolonifera Prevents Soluble
      Amyloid Beta-Induced Cognitive Dysfunction in Aging Rats.
AB  - Fucosterol from edible brown seaweeds has various biological activities,
      including anti-inflammatory, anti-adipogenic, antiphotoaging, anti
      acetylcholinesterase, and anti-beta-secretase 1 activities. However, little is
      known about its effects on soluble amyloid beta peptide (sAbeta)-induced
      endoplasmic reticulum (ER) stress and cognitive impairment. Fucosterol was
      isolated from the edible brown seaweed Ecklonia stolonifera, and its
      neuroprotective effects were analyzed in primary hippocampal neurons and in aging
      rats. Fucosterol attenuated sAbeta1-42-induced decrease in the viability of
      hippocampal neurons and downregulated sAbeta1-42-induced increase in glucose
      regulated protein 78 (GRP78) expression in hippocampal neurons via activation of
      tyrosine receptor kinase B-mediated ERK1/2 signaling. Fucosterol co-infusion
      attenuated sAbeta1-42-induced cognitive impairment in aging rats via
      downregulation of GRP78 expression and upregulation of mature brain-derived
      neurotrophic factor expression in the dentate gyrus. Fucosterol might be
      beneficial for the management of cognitive dysfunction via suppression of aging
      induced ER stress.

PMID- 30301142
TI  - Gut Microbiota and Iron: The Crucial Actors in Health and Disease.
AB  - Iron (Fe) is a highly ample metal on planet earth (~35% of the Earth's mass) and
      is particularly essential for most life forms, including from bacteria to
      mammals. Nonetheless, iron deficiency is highly prevalent in developing
      countries, and oral administration of this metal is so far the most effective
      treatment for human beings. Notably, the excessive amount of unabsorbed iron
      leave unappreciated side effects at the highly interactive host-microbe interface
      of the human gastrointestinal tract. Recent advances in elucidating the molecular
      basis of interactions between iron and gut microbiota shed new light(s) on the
      health and pathogenesis of intestinal inflammatory diseases. We here aim to
      present the dynamic modulation of intestinal microbiota by iron availability, and
      conversely, the influence on dietary iron absorption in the gut. The central part
      of this review is intended to summarize our current understanding about the
      effects of luminal iron on host-microbe interactions in the context of human
      health and disease.

PMID- 30301141
TI  - In Field Fruit Sizing Using A Smart Phone Application.
AB  - In field (on tree) fruit sizing has value in assessing crop health and for yield
      estimation. As the mobile phone is a sensor and communication rich device carried
      by almost all farm staff, an Android application ("FruitSize") was developed for
      measurement of fruit size in field using the phone camera, with a typical
      assessment rate of 240 fruit per hour achieved. The application was based on
      imaging of fruit against a backboard with a scale using a mobile phone, with
      operational limits set on camera to object plane angle and camera to object
      distance. Image processing and object segmentation techniques available in the
      OpenCV library were used to segment the fruit from background in images to obtain
      fruit sizes. Phone camera parameters were accessed to allow calculation of fruit
      size, with camera to fruit perimeter distance obtained from fruit allometric
      relationships between fruit thickness and width. Phone geolocation data was also
      accessed, allowing for mapping fruits of data. Under controlled lighting, RMSEs
      of 3.4, 3.8, 2.4, and 2.0 mm were achieved in estimation of avocado, mandarin,
      navel orange, and apple fruit diameter, respectively. For mango fruit, RMSEs of
      5.3 and 3.7 mm were achieved on length and width, benchmarked to manual caliper
      measurements, under controlled lighting, and RMSEs of 5.5 and 4.6 mm were
      obtained in-field under ambient lighting.

PMID- 30301143
TI  - Role of Natural Volatiles and Essential Oils in Extending Shelf Life and
      Controlling Postharvest Microorganisms of Small Fruits.
AB  - Small fruits are a multi-billion dollar industry in the US, and are economically
      important in many other countries. However, they are perishable and susceptible
      to physiological disorders and biological damage. Food safety and fruit quality
      are the major concerns of the food chain from farm to consumer, especially with
      increasing regulations in recent years. At present, the industry depends on
      pesticides and fungicides to control food spoilage organisms. However, due to
      consumer concerns and increasing demand for safer produce, efforts are being made
      to identify eco-friendly compounds that can extend the shelf life of small
      fruits. Most volatiles and essential oils produced by plants are safe for humans
      and the environment, and lots of research has been conducted to test the in vitro
      efficacy of single-compound volatiles or multi-compound essential oils on various
      microorganisms. However, there are not many reports on their in vivo (in storage)
      and In situ (in the field) applications. In this review, we discuss the efficacy,
      minimum inhibitory concentrations, and mechanisms of action of volatiles and
      essential oils that control microorganisms (bacteria and fungi) on small fruits
      such as strawberries, raspberries, blueberries, blackberries, and grapes under
      the three conditions.

PMID- 30301139
TI  - Crosstalk between NF-kappaB and Nucleoli in the Regulation of Cellular
      Homeostasis.
AB  - Nucleoli are emerging as key sensors of cellular stress and regulators of the
      downstream consequences on proliferation, metabolism, senescence, and apoptosis.
      NF-kappaB signalling is activated in response to a similar plethora of stresses,
      which leads to modulation of cell growth and death programs. While nucleolar and
      NF-kappaB pathways are distinct, it is increasingly apparent that they converge
      at multiple levels. Exposure of cells to certain insults causes a specific type
      of nucleolar stress that is characterised by degradation of the PolI complex
      component, TIF-IA, and increased nucleolar size. Recent studies have shown that
      this atypical nucleolar stress lies upstream of cytosolic IkappaB degradation and
      NF-kappaB nuclear translocation. Under these stress conditions, the RelA
      component of NF-kappaB accumulates within functionally altered nucleoli to
      trigger a nucleophosmin dependent, apoptotic pathway. In this review, we will
      discuss these points of crosstalk and their relevance to anti-tumour mechanism of
      aspirin and small molecule CDK4 inhibitors. We will also briefly the discuss how
      crosstalk between nucleoli and NF-kappaB signalling may be more broadly relevant
      to the regulation of cellular homeostasis and how it may be exploited for
      therapeutic purpose.

PMID- 30301144
TI  - Microenvironmental pH and Exosome Levels Interplay in Human Cancer Cell Lines of
      Different Histotypes.
AB  - Exosomes are extracellular nanovesicles primarily involved in the pathogenesis of
      many diseases including cancer. This study was set out from recent evidence that
      extracellular acidity may increase the exosome release by cancer cells. However,
      this preliminary evidence did not provide solid information on whether the pH
      dependent exosome over-release represents a common feature of all cancers. To the
      purpose of demonstrating that cancer acidity is a major determinant in inducing
      an increased exosome release by human cancer cells, we evaluated human tumor cell
      lines deriving from either colon, breast, prostate cancers, melanoma, or
      osteosarcoma. All cell lines were cultured in either the current 7.4 pH or the
      typical pH of cancer that is 6.5. The levels of released extracellular vesicles
      were measured by protein counts, nanoparticle tracking analysis (NTA), and
      nanoscale flow cytometry. The results showed that pH 6.5 induced a remarkable
      increase in exosome release, and buffering the medium significantly reduced the
      exosome release in all cancers. With these results, we provide, for the first
      time, evidence that tumor acidity and exosome levels represent common cancer
      phenotypes.

PMID- 30301145
TI  - Calculating Intake of Dietary Risk Components Used in the Global Burden of
      Disease Studies from the What We Eat in America/National Health and Nutrition
      Examination Surveys.
AB  - Disability adjusted life years (DALYs) is a health burden metric that combines
      years of life lost due to disease disability and premature mortality. The Global
      Burden of Disease (GBD) has been using DALYs to determine the health burden
      associated with numerous health risks, including risks associated with dietary
      intakes, at the global and national level. To translate such information at the
      food level in the U.S., variables in What We Eat in America (WWEIA) need to be
      aligned with those in the GBD. In this paper, we develop the necessary new
      variables needed to account for differences in definitions and units between
      WWEIA and the GBD. We use the Food Patterns Equivalents Database, Food Patterns
      Equivalents Ingredient Database, Food and Nutrient Database for Dietary Studies,
      and Standard Reference databases that provide data for WWEIA to develop food
      group and nutrient variables that align with definitions and units used in the
      GBD. Considerable effort was needed to disaggregate mixed dishes to GBD
      components. We also developed a new "non-starchy" vegetable variable, since the
      GBD vegetables do not include potatoes and corn, and we report fruits and
      vegetables in grams instead of household measures. New fiber variables were
      created to avoid double counting of fiber from legumes, whole grains, fruits, and
      vegetables. Regression analyses were used to predict trans-fat content for foods
      in WWEIA with missing or incomplete information. The majority of foods in various
      U.S. Department of Agriculture (USDA) categories contain multiple GBD food groups
      (e.g., vegetables, whole grains, and processed meat). For most nutrients
      considered in the GBD, composition is more evenly distributed across the main
      food categories; however, seafood omega-3 fats were predominantly from either
      protein foods or mixed dishes and sugar sweetened beverages were from a single
      category. Dietary intakes in the U.S. fall short of recommendations for all food
      groups/nutrients with established theoretical minimum-risk targets in GBD. To our
      knowledge, this is the first approach that aligns WWEIA intake variables with
      those used in the health burden-based GBD reports. These methods will facilitate
      researchers to begin comparing data from the U.S. with that from other countries,
      as well as assess food sustainability performances by concomitantly evaluating
      DALYs for environmental and nutritional impacts.

PMID- 30301146
TI  - Molecular Targets Modulated by Fangchinoline in Tumor Cells and Preclinical
      Models.
AB  - Despite tremendous progress made during the last few decades in the treatment
      options for cancer, compounds isolated from Mother Nature remain the mainstay for
      therapy of various malignancies. Fangchinoline, initially isolated from the dried
      root of Stephaniae tetrandrine, has been found to exhibit diverse pharmacological
      effects including significant anticancer activities both in tumor cell lines and
      selected preclinical models. This alkaloid appears to act by modulating the
      activation of various important oncogenic molecules involved in tumorigenesis
      leading to a significant decrease in aberrant proliferation, survival and
      metastasis of tumor cells. This mini-review briefly describes the potential
      effects of fangchinoline on important hallmarks of cancer and highlights the
      molecular targets modulated by this alkaloid in various tumor cell lines and
      preclinical models.

PMID- 30301147
TI  - Prostaglandin D2 Induces Ca2+ Sensitization of Contraction without Affecting
      Cytosolic Ca2+ Level in Bronchial Smooth Muscle.
AB  - Prostaglandin D2 (PGD2) is one of the key lipid mediators of allergic airway
      inflammation, including bronchial asthma. However, the role of PGD2 in the
      pathogenesis of asthma is not fully understood. In the present study, the effect
      of PGD2 on smooth muscle contractility of the airways was determined to elucidate
      its role in the development of airway hyperresponsiveness (AHR). In isolated
      bronchial smooth muscles (BSMs) of naive mice, application of PGD2 (10-9-10-5 M)
      had no effect on the baseline tension. However, when the tissues were
      precontracted partially with 30 mM K+ (in the presence of 10-6 M atropine), PGD2
      markedly augmented the contraction induced by the high K+ depolarization. The
      PGD2-induced augmentation of contraction was significantly inhibited both by 10-6
      M laropiprant (a selective DP1 antagonist) and 10-7 M Y-27632 (a Rho-kinase
      inhibitor), indicating that a DP1 receptor-mediated activation of Rho-kinase is
      involved in the PGD2-induced BSM hyperresponsiveness. Indeed, the GTP-RhoA pull
      down assay revealed an increase in active form of RhoA in the PGD2-treated mouse
      BSMs. On the other hand, in the high K+-depolarized cultured human BSM cells,
      PGD2 caused no further increase in cytosolic Ca2+ concentration. These findings
      suggest that PGD2 causes RhoA/Rho-kinase-mediated Ca2+ sensitization of BSM
      contraction to augment its contractility. Increased PGD2 level in the airways
      might be a cause of the AHR in asthma.

PMID- 30301148
TI  - Tailoring of Magnetic Properties of NiO/Ni Composite Particles Fabricated by
      Pulsed Laser Irradiation.
AB  - We present NiO/Ni composite particles with face-centered cubic (fcc) structure
      prepared by a pulsed laser irradiation of NiO nanoparticles dispersed in liquid.
      The sizes of particles and the Ni content in NiO/Ni composites were controlled by
      tuning the laser parameters, such as laser fluence and irradiation time. We found
      that the weight fraction of Ni has a significant impact on magnetic properties of
      composite particles. Large exchange bias (HEB) and coercivity field (HC) were
      observed at 5 K due to the creation of heterojunctions at interfaces of
      ferromagnetic Ni and antiferromagnetic NiO. For the NiO/Ni composites with 80% of
      NiO we have observed the largest values of exchange bias (175 Oe) and coercive
      field (950 Oe), but the increase of Ni weight fraction resulted in the decrease
      of both HC and HEB values.

PMID- 30301149
TI  - Knockdown of LXRalpha Inhibits Goat Intramuscular Preadipocyte Differentiation.
AB  - Goat intramuscular fat (IMF) content is mainly determined by the processes of
      intramuscular preadipocytes adipogenic differentiation and mature adipocyte lipid
      accumulation. However, the underlying regulators of these biological processes
      remain largely unknown. Here, we report that the expression of Liver X receptor
      alpha (LXRalpha) reaches a peak at early stage and then gradually decreases
      during goat intramuscular adipogenesis. Knockdown of LXRalpha mediated by two
      independent siRNAs significantly inhibits intramuscular adipocytes lipid
      accumulation and upregulates preadipocytes marker- preadipocyte factor 1 (pref1)
      expression. Consistently, siRNA treatments robustly decrease mRNA level of
      adipogenic related genes, including CCAAT enhancer binding protein alpha
      (Cebpalpha), Peroxisome proliferator activated receptor gamma (Pparg), Sterol
      regulatory element binding protein isoform 1c (Srebp1c), Fatty acids binding
      protein (aP2) and Lipoprotein lipase (Lpl). Next, adenovirus overexpression of
      LXRalpha does not affect intramuscular adipocytes adipogenesis manifested by Oil
      Red O signal measurement and adipogenic specific genes detection. Mechanically,
      we found that both CCAAT enhancer binding protein beta (Cebpbeta) and Kruppel
      like factor 8 (Klf8) are potential targets of LXRalpha, indicated by having
      putative binding sites of LXRalpha at the promoter of these genes and similar
      expression pattern during adipogenesis comparing to LXRalpha. Importantly, mRNA
      levels of Cebpbeta and Klf8 are downregulated significantly in goat LXRalpha
      knockdown intramuscular adipocyte. These results demonstrate that loss function
      of LXRalpha inhibits intramuscular adipogenesis possibly through down-regulation
      of Cebpbeta and Klf8. Our research will provide new insights into mechanical
      regulation of goat IMF deposition.

PMID- 30301150
TI  - Ganoderma tsugae Inhibits the SREBP-1/AR Axis Leading to Suppression of Cell
      Growth and Activation of Apoptosis in Prostate Cancer Cells.
AB  - Recent research suggests that the activation of lipid biosynthesis (lipogenesis)
      is linked with prostate cancer (PCa) malignancy. Sterol regulatory element
      binding protein-1 (SREBP-1) is a key transcriptional regulator controlling
      lipogenesis. Moreover, androgen receptor (AR) has been well defined to play an
      important role in lethal PCa aggressiveness from androgen-responsive to
      castration-resistant status. In this study, we showed that the quality-assured
      Ganoderma tsugae ethanol extract (GTEE), a Chinese natural and herbal product,
      significantly inhibited expression of SREBP-1 and its downstream genes associated
      with lipogenesis in PCa cells. Through inhibiting SREBP-1, GTEE reduced the
      levels of intracellular fatty acids and lipids in PCa cells. Importantly, GTEE
      also downregulated the expression of AR and prostate-specific antigen (PSA) in
      both androgen-responsive and castration-resistant PCa cells. By blocking the
      SREBP-1/AR axis, GTEE suppressed cell growth and progressive behaviors, as well
      as activating the caspase-dependent apoptotic pathway in PCa cells. These data
      provide a new molecular basis of GTEE for the development of a potential
      therapeutic approach to treat PCa malignancy.

PMID- 30301152
TI  - Tumor-Stroma Cross-Talk in Human Pancreatic Ductal Adenocarcinoma: A Focus on the
      Effect of the Extracellular Matrix on Tumor Cell Phenotype and Invasive
      Potential.
AB  - The extracellular matrix (ECM) in the tumor microenvironment modulates the cancer
      cell phenotype, especially in pancreatic ductal adenocarcinoma (PDAC), a tumor
      characterized by an intense desmoplastic reaction. Because the epithelial-to
      mesenchymal transition (EMT), a process that provides cancer cells with a
      metastatic phenotype, plays an important role in PDAC progression, the authors
      aimed to explore in vitro the interactions between human PDAC cells and ECM
      components of the PDAC microenvironment, focusing on the expression of EMT
      markers and matrix metalloproteinases (MMPs) that are able to digest the basement
      membrane during tumor invasion. EMT markers and the invasive potential of HPAF
      II, HPAC, and PL45 cells grown on different ECM substrates (fibronectin, laminin,
      and collagen) were analyzed. While N-cadherin, alphaSMA, and type I collagen were
      not significantly affected by ECM components, the E-cadherin/beta-catenin complex
      was highly expressed in all the experimental conditions, and E-cadherin was
      upregulated by collagen in PL45 cells. Cell migration was unaffected by
      fibronectin and delayed by laminin. In contrast, collagen significantly
      stimulated cell migration and the secretion of MMPs. This study's results showed
      that ECM components impacted cell migration and invasive potential differently.
      Collagen exerted a more evident effect, providing new insights into the
      understanding of the intricate interplay between ECM molecules and cancer cells,
      in order to find novel therapeutic targets for PDAC treatment.

PMID- 30301151
TI  - Dietary Patterns in Primary School are of Prospective Relevance for the
      Development of Body Composition in Two German Pediatric Populations.
AB  - This study performed comparative analyses in two pediatric cohorts to identify
      dietary patterns during primary school years and examined their relevance to body
      composition development. Nutritional and anthropometric data at the beginning of
      primary school and two or four years later were available from 298 and 372
      participants of IDEFICS-Germany (Identification and prevention of Dietary-induced
      and lifestyle-induced health Effects In Children and infants Study) and the KOPS
      (Kiel Obesity Prevention Study) cohort, respectively. Principal component
      analyses (PCA) and reduced rank regression (RRR) were used to identify dietary
      patterns at baseline and patterns of change in food group intake during primary
      school years. RRR extracted patterns explaining variations in changes in body
      mass index (BMI), fat mass index (FMI), and waist-to-height-ratio (WtHR).
      Associations between pattern adherence and excess gain in BMI, FMI, or WtHR
      (>75th percentile) during primary school years were examined using logistic
      regression. Among PCA patterns, only a change towards a more Mediterranean food
      choice during primary school years were associated with a favorable body
      composition development in IDEFICS-Germany (p < 0.05). In KOPS, RRR patterns
      characterized by a frequent consumption of fast foods or starchy carbohydrate
      foods were consistently associated with an excess gain in BMI and WtHR (all p <
      0.005). In IDEFICS-Germany, excess gain in BMI, FMI, and WtHR were predicted by a
      frequent consumption of nuts, meat, and pizza at baseline and a decrease in the
      consumption frequency of protein sources and snack carbohydrates during primary
      school years (all p < 0.01). The study confirms an adverse impact of fast food
      consumption on body composition during primary school years. Combinations of
      protein and carbohydrate sources deserve further investigation.

PMID- 30301153
TI  - Synthesis and Evaluation of Novel Ligustrazine Derivatives as Multi-Targeted
      Inhibitors for the Treatment of Alzheimer's Disease.
AB  - A series of novel ligustrazine derivatives 8a-r were designed, synthesized, and
      evaluated as multi-targeted inhibitors for anti-Alzheimer's disease (AD) drug
      discovery. The results showed that most of them exhibited a potent ability to
      inhibit both ChEs, with a high selectivity towards AChE. In particular, compounds
      8q and 8r had the greatest inhibitory abilities for AChE, with IC50 values of
      1.39 and 0.25 nM, respectively, and the highest selectivity towards AChE (for 8q,
      IC50 BuChE/IC50 AChE = 2.91 * 106; for 8r, IC50 BuChE/IC50 AChE = 1.32 * 107). Of
      note, 8q and 8r also presented potent inhibitory activities against Abeta
      aggregation, with IC50 values of 17.36 uM and 49.14 uM, respectively. Further
      cellular experiments demonstrated that the potent compounds 8q and 8r had no
      obvious cytotoxicity in either HepG2 cells or SH-SY5Y cells, even at a high
      concentration of 500 MUM. Besides, a combined Lineweaver-Burk plot and molecular
      docking study revealed that these compounds might act as mixed-type inhibitors to
      exhibit such effects via selectively targeting both the catalytic active site
      (CAS) and the peripheral anionic site (PAS) of AChEs. Taken together, these
      results suggested that further development of these compounds should be of great
      interest.

PMID- 30301154
TI  - Fine-Scale Source Apportionment Including Diesel-Related Elemental and Organic
      Constituents of PM2.5 across Downtown Pittsburgh.
AB  - Health effects of fine particulate matter (PM2.5) may vary by composition, and
      the characterization of constituents may help to identify key PM2.5 sources, such
      as diesel, distributed across an urban area. The composition of diesel
      particulate matter (DPM) is complicated, and elemental and organic carbon are
      often used as surrogates. Examining multiple elemental and organic constituents
      across urban sites, however, may better capture variation in diesel-related
      impacts, and help to more clearly separate diesel from other sources. We designed
      a "super-saturation" monitoring campaign of 36 sites to capture spatial variance
      in PM2.5 and elemental and organic constituents across the downtown Pittsburgh
      core (~2.8 km2). Elemental composition was assessed via inductively-coupled
      plasma mass spectrometry (ICP-MS), organic and elemental carbon via thermal
      optical reflectance, and organic compounds via thermal desorption gas
      chromatography mass-spectrometry (TD-GCMS). Factor analysis was performed
      including all constituents-both stratified by, and merged across, seasons.
      Spatial patterning in the resultant factors was examined using land use
      regression (LUR) modelling to corroborate factor interpretations. We identified
      diesel-related factors in both seasons; for winter, we identified a five-factor
      solution, describing a bus and truck-related factor [black carbon (BC),
      fluoranthene, nitrogen dioxide (NO2), pyrene, total carbon] and a fuel oil
      combustion factor (nickel, vanadium). For summer, we identified a nine-factor
      solution, which included a bus-related factor (benzo[ghi]fluoranthene, chromium,
      chrysene, fluoranthene, manganese, pyrene, total carbon, total elemental carbon,
      zinc) and a truck-related factor (benz[a]anthracene, BC, hopanes, NO2, total
      PAHs, total steranes). Geographic information system (GIS)-based emissions source
      covariates identified via LUR modelling roughly corroborated factor
      interpretations.

PMID- 30301155
TI  - Life Course Effects of Socioeconomic and Lifestyle Factors on Metabolic Syndrome
      and 10-Year Risk of Cardiovascular Disease: A Longitudinal Study in Taiwan
      Adults.
AB  - The objective of the study was to explore the dynamic effects of socioeconomic
      status (SES) and lifestyle behaviors on the risks of metabolic syndrome (MS) or
      cardiovascular disease (CVD) in life course. The data of 12,825 subjects (6616
      males and 6209 females) who underwent repeated examinations and answered repeated
      questionnaires from 2006 to 2014 at the Major Health Screening Center in Taiwan,
      was collected and analyzed. The trajectory of trends in the subjects' SES and
      lifestyle mobility over time was observed, and the effects of factors with
      potential impacts on health were tested and analyzed using multiple logistic
      regression and a generalized estimated equation model. A 10% increase in MS
      prevalence was observed over the nine-year period. The average Framingham CVD
      score for people with MS was estimated to be about 1.4% (SD = 1.5%). Except for
      middle-aged women, marriage was found to raise the risk of CVD, whereas
      increasing education and work promotions independently reduced CVD risk for the
      majority of subjects. However, the risk of CVD was raised by half for young men
      who had a job or lost a job in comparison to continuously unemployed young men.
      Physical activity was only found to be advantageous for disease prevention in
      those aged less than 40 years; increased exercise levels were useless for
      reducing CVD risk among older men. Alcohol drinking and betel chewing caused
      increased CVD risk in the old and young subjects, respectively, whereas
      vegetarian diets and vitamin C/E intake were helpful in preventing CVD, even if
      those habits were ceased in later life. For middle-aged women, getting sufficient
      sleep reduced CVD risk. We concluded that SES and lifestyle behaviors may have
      different effects on health over time, among various populations. Accordingly,
      suggestions can be provided to healthcare workers in designing health promotion
      courses for people at different life stages.

PMID- 30301156
TI  - Pulse Ultrasonic Cure Monitoring of the Pultrusion Process.
AB  - This article discusses the results of a series of experiments on pulse ultrasonic
      cure monitoring of carbon fiber reinforced plastics applied to the pultrusion
      process. The aim of this study is to validate the hypothesis that pulse
      ultrasonic cure monitoring can be applied (a) for profiles having small cross
      sections such as 7 mm * 0.5 m m and (b) within the environment of the pultrusion
      process. Ultrasonic transducers are adhesively bonded to the pultrusion tool as
      actuators and sensors. The time-of-flight and the amplitude of an ultrasonic wave
      are analyzed to deduce the current curing state of the epoxy matrix. The
      experimental results show that ultrasonic cure monitoring is indeed applicable
      even to very thin cross sections. However, significant challenges can be reported
      when the techniques are used during the pultrusion process.

PMID- 30301157
TI  - Non-Stationary Platform Inverse Synthetic Aperture Radar Maneuvering Target
      Imaging Based on Phase Retrieval.
AB  - As a powerful signal processing tool for imaging moving targets, placing radar on
      a non-stationary platform (such as an aerostat) is a future direction of Inverse
      Synthetic Aperture Radar (ISAR) systems. However, more phase errors are
      introduced into the received signal due to the instability of the radar platform,
      making it difficult for popular algorithms to accurately perform motion
      compensation, which leads to severe effects in the resultant ISAR images.
      Moreover, maneuvering targets may have complex motion whose motion parameters are
      unknown to radar systems. To overcome the issue of non-stationary platform ISAR
      autofocus imaging, a high-resolution imaging method based on the phase retrieval
      principle is proposed in this paper. Firstly, based on the spatial geometric and
      echo models of the ISAR maneuvering target, we can deduce that the radial motion
      of the radar platform or the vibration does not affect the modulus of the ISAR
      echo signal, which provides a theoretical basis for the phase recovery theory for
      the ISAR imaging. Then, we propose an oversampling smoothness (OSS) phase
      retrieval algorithm with prior information, namely, the phase of the blurred
      image obtained by the classical imaging algorithm replaces the initial random
      phase in the original OSS algorithm. In addition, the size of the support domain
      of the OSS algorithm is set with respect to the blurred target image.
      Experimental simulation shows that compared with classical imaging methods, the
      proposed method can obtain the resultant motion-compensated ISAR image without
      estimating the radar platform and maneuvering target motion parameters, wherein
      the fictitious target is perfectly focused.

PMID- 30301158
TI  - Effect of Cetylpyridinium Chloride (CPC) on Colony Formation of Common
      Nontuberculous Mycobacteria.
AB  - Cetylpyridinium chloride (CPC) is widely used to decontaminate water samples for
      the cultivation of nontuberculous mycobacteria (NTM). The rationale for using CPC
      is that it kills more non mycobacteria than NTM and thereby prevents the
      outgrowth and detection of mycobacterial colonies on solid media. The few CPC
      susceptibility measurements that have been published, suggest that CPC
      decontamination does kill significant numbers of NTM. We confirm that observation
      here and further demonstrate that CPC-susceptibility varied significantly by one
      log between representative NTM species and between strains of the same species.
      CPC-susceptibility was the same for cells collected from cultures or water
      acclimated (P = 0.6485, T-test) and CPC-susceptibility was relatively similar
      over the range of commonly employed CPC dosages. We conclude that use of CPC as
      decontaminating agent may lead to failure to recover an NTM isolate and
      considerable underestimates of NTM numbers.

PMID- 30301159
TI  - The Acute Effects of Foam Rolling on Fatigue-Related Impairments of Muscular
      Performance.
AB  - The purpose of this study was to examine the effects of self-myofascial release
      (MFR) via foam rolling immediately following strenuous activity on acute fatigue
      related impairments of muscular performance. Healthy male (n = 16) and female (n
      = 9) subjects visited the laboratory three separate times. During visit 1,
      subjects were familiarized with performance testing procedures and the foam
      rolling and fatigue protocols. For visits 2 and 3, subjects were (T1) assessed
      for vertical jump height, velocity, and power and dynamic reaction time (DRT).
      Subjects then performed the exercise fatigue protocol, followed by either a foam
      rolling treatment (MFR) or seated rest (CON). Immediately after, subjects
      repeated the performance tests (T2). CON resulted in a greater percent decline
      from T1-T2 for average power (p = 0.03), average velocity (p = 0.02), and peak
      power (p = 0.03) than the MFR treatment. No between-treatment differences were
      detected for %? vertical jump height (p = 0.14) or DRT (p = 0.20). According to
      magnitude-based inference analysis, MFR is likely beneficial in attenuating
      fatigue-induced kinematic decrements (i.e., power and velocity). Based on
      magnitude-based inference analysis, MFR is "possibly beneficial" with respect to
      mitigating acute fatigue-related impairment of jump height and dynamic reaction
      time. Results demonstrate the plausible short-term benefits of foam rolling on
      muscular performance decrements associated with acute muscular fatigue from
      exercise.

PMID- 30301160
TI  - Evaluation of Intensity of Sleep Bruxism in Arterial Hypertension.
AB  - Sleep bruxism (SB) is a masticatory muscle activity during sleep that is
      characterized as rhythmic (phasic) or non-rhythmic (tonic). The recent hypothesis
      on the etiology of SB supports the role of the central and autonomic nervous
      systems. Therefore, in this study, we aimed to assess the intensity of SB in
      patients with arterial hypertension. A total of 70 adults participated in this
      study: 35 patients with hypertension (study group) and 35 normotensive subjects
      (control group). Data were recorded using home portable cardiorespiratory
      polygraphy. The bruxism episode index (BEI) in the study group was found to be
      significantly higher compared to the control group (3.4 +/- 3.25 vs. 2.35 +/-
      2.29, p = 0.04). Hypertension, higher body mass index (BMI), lower values of mean
      oxygen saturation (SpO2), and a higher percentage of SpO2 < 90% constituted
      independent risk factors for increased BEI. These results suggest the need for
      special oral care in hypertensive patients, patients with higher BMI, lower
      values of SpO2 and a higher percentage of SpO2 < 90%.

PMID- 30301161
TI  - A Marine Diterpenoid Modulates the Proteasome Activity in Murine Macrophages
      Stimulated with LPS.
AB  - The proteasome is an intracellular complex that degrades damaged or unfolded
      proteins and participates in the regulation of several processes. The
      immunoproteasome is a specialized form that is expressed in response to
      proinflammatory signals and is particularly abundant in immune cells. In a
      previous work, we found an anti-inflammatory effect in a diterpenoid extracted
      from the octocoral Pseudopterogorgia acerosa, here called compound 1. This
      compound prevented the degradation of inhibitor kappaB alpha (IkappaBalpha) and
      the subsequent activation of nuclear factor kappaB (NFkappaB), suggesting that
      this effect might be due to inhibition of the ubiquitin-proteasome system. Here
      we show that compound 1 inhibits the proteasomal chymotrypsin-like activity (CTL)
      of murine macrophages in the presence of lipopolysaccharide (LPS) but not in its
      absence. This effect might be due to the capacity of this compound to inhibit the
      activity of purified immunoproteasome. The compound inhibits the cell surface
      expression of major histocompatibility complex (MHC)-I molecules and the
      production of proinflammatory cytokines induced by LPS in vitro and in vivo,
      respectively. Molecular docking simulations predicted that compound 1 selectively
      binds to the catalytic site of immunoproteasome subunits beta1i and beta5i, which
      are responsible for the CTL activity. Taken together these findings suggest that
      the compound could be a selective inhibitor of the immunoproteasome, and hence
      could pave the way for its future evaluation as a candidate for the treatment of
      inflammatory disorders and autoimmune diseases.

PMID- 30301162
TI  - Elucidating Functions of FleQ in Xanthomonas oryzae pv. oryzae by Comparative
      Proteomic and Phenotypic Analyses.
AB  - To acclimate to different environments, gene expression has to be controlled
      using diverse transcriptional activators. FleQ activates sigma54-dependent
      transcription initiation and regulates flagellar biosynthesis and other
      mechanisms in several bacteria. Xanthomonas oryzae pv. oryzae (Xoo), which is a
      causal agent of bacterial leaf blight on rice, lacking FleQ loses swimming
      motility and virulence is not altered. However, other biological mechanisms
      related with FleQ in Xoo are unknown. In this study, we generated the FleQ
      overexpressing strain, Xoo(FleQ), and knockout mutant, XooDeltafleQ. To predict
      the mechanisms affected by FleQ, label-free shotgun comparative proteomics was
      carried out. Based on proteomic results, we performed diverse phenotypic assays.
      Xoo(FleQ) had reduced ability to elicit disease symptoms and exopolysaccharide
      production. Additionally, the ability of XooDeltafleQ(EV) (empty vector) and
      Xoo(FleQ) to form biofilm was decreased. Swarming motility of XooDeltafleQ(EV)
      was abolished, but was only reduced for Xoo(FleQ). Additionally, abnormal
      twitching motility was observed in both strains. Siderophore production of
      Xoo(FleQ) was enhanced in iron-rich conditions. The proteomic and phenotypic
      analyses revealed that FleQ is involved in flagellar-dependent motility and other
      mechanisms, including symptom development, twitching motility, exopolysaccharide
      production, biofilm formation, and siderophore production. Thus, this study
      provides fundamental information about a sigma54-dependent transcription
      activator in Xoo.

PMID- 30301163
TI  - Unliganded Progesterone Receptor Governs Estrogen Receptor Gene Expression by
      Regulating DNA Methylation in Breast Cancer Cells.
AB  - Breast cancer prognosis and response to endocrine therapy strongly depends on the
      expression of the estrogen and progesterone receptors (ER and PR, respectively).
      Although much is known about ERalpha gene (ESR1) regulation after hormonal
      stimulation, how it is regulated in hormone-free condition is not fully
      understood. We used ER-/PR-positive breast cancer cells to investigate the role
      of PR in ESR1 regulation in the absence of hormones. We show that PR binds to the
      low-methylated ESR1 promoter and maintains both gene expression and DNA
      methylation of the ESR1 locus in hormone-deprived breast cancer cells. Depletion
      of PR reduces ESR1 expression, with a concomitant increase in gene promoter
      methylation. The high amount of methylation in the ESR1 promoter of PR-depleted
      cells persists after the stable re-expression of PR and inhibits PR binding to
      this genomic region. As a consequence, the rescue of PR expression in PR-depleted
      cells is insufficient to restore ESR1 expression. Consistently, DNA methylation
      impedes PR binding to consensus progesterone responsive elements. These findings
      contribute to understanding the complex crosstalk between PR and ER and suggest
      that the analysis of ESR1 promoter methylation in breast cancer cells can help to
      design more appropriate targeted therapies for breast cancer patients.

PMID- 30301165
TI  - Seasonal Change in Distribution and Heat Coma Temperature of Oceanic Skaters,
      Halobates (Insecta, Heteroptera: Gerridae).
AB  - A series of studies were conducted during two cruises between Tokyo and Honolulu
      in September 2010 and from February to March 2012. The aims of the studies were
      to (1) compare the distribution of three species of Halobates oceanic skaters, H.
      germanus, H. micans, and H. sericeus, with respect to their temperature limits;
      (2) identify the lower temperature limit of H. sericeus, the species that
      displays the widest distribution range (40 degrees N-35 degrees S) latitude; and
      (3) test the hypothesis that H. sericeus can change their temperature tolerance
      to adapt to seasonal changes in sea surface temperatures. The heat coma
      temperature (HCT) was measured during the two cruises and the values were
      compared between the two populations of H. sericeus. The species collected in
      September 2010 were H. germanus, H. micans, and H. sericeus. H. sericeus was
      dominant, occupying more than 90% of the collecting sites. H. germanus and H.
      micans were collected in the northern and western part of the cruise track (29-34
      degrees N, 141-151 degrees E), and not in the southern and eastern part. The
      population density of these two species was 9000-150,000/km2 in the first cruise,
      which took place in summer. On the other hand, H. sericeus was collected
      throughout the cruise track during that cruise. The population density of H.
      sericeus was relatively high, at 4000-310,000/km2, in the southern and eastern
      part of the cruise track (19-29 degrees N, 152 degrees E-165 degrees W). In
      February and March 2012, only H. sericeus was collected at a density of 17,000
      80,000/km2 and only in the eastern and southern part, at 25 degrees -28 degrees
      N, 169 degrees E-178 degrees W. No Halobates oceanic skaters were found in the
      western or northern part (30 degrees N and further north, 159 degrees E and
      further west) during that cruise. The lower limit for the inhabitation of sea
      surface temperatures appeared to be 27.8  degrees C or slightly lower for H.
      germanus and H. micans, but was 22.1  degrees C or slightly lower for H.
      sericeus. H. sericeus specimens, mostly adults, that had been collected during
      the two cruises were used in heat coma experiments. Summer specimens showed
      significantly higher heat coma temperatures (HCTs) than the winter specimens.
      This difference in HCTs may be the result of relatively long term temperature
      acclimation in the summer or winter for the adults that inhabit the temperate and
      subtropical areas along the cruise tracks between Tokyo and Honolulu in the
      Pacific Ocean. This temperature plasticity of H. sericeus may be related to the
      wider latitude area inhabited by this species (main range: 40 degrees N-25
      degrees S).

PMID- 30301166
TI  - Dispersal in Host-Parasitoid Interactions: Crop Colonization by Pests and
      Specialist Enemies.
AB  - Interactions of insect pests and their natural enemies increasingly are being
      considered from a metapopulation perspective, with focus on movements of
      individuals among habitat patches (e.g., individual crop fields). Biological
      control may be undercut in short-lived crops as natural enemies lag behind the
      pests in colonizing newly created habitat. This hypothesis was tested by
      assessing parasitism of cereal leaf beetle (Oulema melanopus) and alfalfa weevil
      (Hypera postica) larvae at varying distances along transects into newly planted
      fields of small grains and alfalfa in northern Utah. The rate of parasitism of
      cereal leaf beetles and alfalfa weevils by their host-specific parasitoids
      (Tetrastichus julis (Eulophidae) and Bathyplectes curculionis (Ichneumonidae),
      respectively) was determined for earliest maturing first generation host larvae.
      Rates of parasitism did not vary significantly with increasing distance into a
      newly planted field (up to 250-700 m in individual experiments) from the nearest
      source field from which pest and parasitoid adults may have immigrated. These
      results indicate strong, rapid dispersal of the parasitoids in pursuing their
      prey into new habitat. Thus, across the fragmented agricultural landscape of
      northern Utah, neither the cereal leaf beetle nor the alfalfa weevil initially
      gained substantial spatial refuge from parasitism by more strongly dispersing
      than their natural enemies into newly created habitat. Additional studies,
      including those of colonization of newly planted crops by generalist pests and
      natural enemies, are called for in assessing these results with a broader
      perspective.

PMID- 30301164
TI  - Comprehensive Description of Fusarium graminearum Pigments and Related Compounds.
AB  - Several studies have explored in depth the biochemistry and genetics of the
      pigments present in Fusarium graminearum, but there is a need to discuss their
      relationship with the mold's observable surface color pattern variation
      throughout its lifecycle. Furthermore, they require basic cataloguing, including
      a description of their major features known so far. Colors are a viable
      alternative to size measurement in growth studies. When grown on yeast extract
      agar (YEA) at 25  degrees C, F. graminearum initially exhibits a whitish
      mycelium, developing into a yellow-orange mold by the sixth day and then turning
      into wine-red. The colors are likely due to accumulation of the golden yellow
      polyketide aurofusarin and the red rubrofusarin, but the carotenoid
      neurosporaxanthin also possibly plays a major role in the yellow or orange
      coloration. Torulene might contribute to red tones, but it perhaps ends up being
      converted into neurosporaxanthin. Culmorin is also present, but it does not
      contribute to the color, though it was initially isolated in pigment studies.
      Additionally, there is the 5-deoxybostrycoidin-based melanin, but it mostly
      occurs in the teleomorph's perithecium. There is still a need to chemically
      quantify the pigments throughout the lifecycle, and analyze their relationships
      and how much each impacts F. graminearum's surface color.

PMID- 30301167
TI  - Microbiota and Phage Therapy: Future Challenges in Medicine.
AB  - An imbalance of bacterial quantity and quality of gut microbiota has been linked
      to several pathologies. New strategies of microbiota manipulation have been
      developed such as fecal microbiota transplantation (FMT); the use of
      pre/probiotics; an appropriate diet; and phage therapy. The presence of
      bacteriophages has been largely underestimated and their presence is a relevant
      component for the microbiome equilibrium. As a promising treatment, phage therapy
      has been extensively used in Eastern Europe to reduce pathogenic bacteria and has
      arisen as a new method to modulate microbiota diversity. Phages have been
      selected and "trained" to infect a wide spectrum of bacteria or tailored to
      infect specific antibiotic resistant bacteria present in patients. The new
      development of genetically modified phages may be an efficient tool to treat the
      gut microbiota dysbiosis associated with different pathologies and increased
      production of bacterial metabolites and subsequently decrease systemic low-grade
      chronic inflammation associated with chronic diseases. Microbiota quality and
      mitochondria dynamics can be remodulated and manipulated by phages to restore the
      equilibrium and homeostasis of the system. Our aim is to highlight the great
      interest for phages not only to eliminate and control pathogenic bacterial
      infection but also in the near future to modulate the microbiota by adding new
      functions to selected bacteria species and rebalance the dynamic among phages and
      bacteria. The challenge for the medicine of tomorrow is to re-think and redesign
      strategies differently and far from our traditional thinking.

PMID- 30301168
TI  - Challenge Studies to Determine the Ability of Foods to Support the Growth of
      Listeria monocytogenes.
AB  - : Listeria monocytogenes is a foodborne pathogen that causes listeriosis, a
      relatively rare, but potentially fatal, disease, with a mortality rate of 20-30%.
      In general, European Regulations require the absence of L. monocytogenes in five
      samples of 25 g before the food has left the producer, but if the food has been
      demonstrated not to support the growth of L. monocytogenes, up to 100 cfu g-1 are
      allowed in the food (except for foods for infants or medical purposes) during its
      shelf-life under reasonably foreseeable storage conditions. It is important for
      food producers to determine if their food supports the growth of L.
      monocytogenes. The European Union Reference Laboratory for L. monocytogenes
      published a Technical Guidance document for conducting shelf-life studies on L.
      monocytogenes in ready-to-eat foods in June 2014. Primarily based on the EURL
      guidance document for conducting challenge studies, the ability of cheese (feta
      and soft goat's milk cheese), cold-smoked salmon, coleslaw, and pork pate to
      support the growth of L. monocytogenes was determined using a starting inoculum
      of approximately 100 cfu g-1. The cheese and pork pate were incubated at 8 
      degrees C for 14 days; the smoked salmon was incubated at 6  degrees C for 5 days
      and 8 degrees C for 9 days; and the coleslaw was incubated at 8  degrees C for 7
      days and 12  degrees C for 14 days. The results showed that the smoked salmon and
      pork pate supported growth, while coleslaw and cheese did not. From this study,
      it is evident that there are factors in food other than pH, water activity, and
      total bacterial count (TBC) that can inhibit the ability of L. monocytogenes to
      grow in food.

PMID- 30301169
TI  - Improvement of Soybean Agrobacterium-Mediated Transformation Efficiency by Adding
      Glutamine and Asparagine into the Culture Media.
AB  - As a genetically modified crop, transgenic soybean occupies the largest global
      scale with its food, nutritional, industrial, and pharmaceutical uses.Efficient
      transformation is a key factor for the improvement of genetically modified
      soybean. At present, the Agrobacterium-mediated method is primarily used for
      soybean transformation, but the efficiency of this method is still relatively low
      (below 5%) compared with rice (above 90%). In this study, we examined the
      influence of l-glutamine and/or l-asparagine on Agrobacterium-mediated
      transformation in soybean and explored the probable role in the process of
      Agrobacterium-mediated transformation. The results showed that when the amino
      acids l-glutamine and l-asparagine were added separately or together to the
      culture medium, the shoot induction frequency, elongation rate, and
      transformation frequency were improved. The combined effects of l-glutamine and l
      asparagine were better than those of l-glutamine and l-asparagine alone. The 50
      mg/L l-glutamine and 50 mg/L l-asparagine together can enhance the transformation
      frequency of soybean by attenuating the expression level of GmPRs (GmPR1, GmPR4,
      GmPR5, and GmPR10) and suppression of the plant defense response. The transgene
      was successfully transmitted to the T1 generation. This study will be useful in
      genetic engineering of soybean.

PMID- 30301170
TI  - Erucic Acid (22:1n-9) in Fish Feed, Farmed, and Wild Fish and Seafood Products.
AB  - The European Food Safety Authority (EFSA) published a risk assessment of erucic
      acid (22:1n-9) in 2016, establishing a Tolerable Daily Intake (TDI) for humans of
      7 mg kg-1 body weight per day. This report largely excluded the contribution of
      erucic acid from fish and seafood, due to this fatty acid often not being
      reported separately in seafood. The Institute of Marine Research (IMR) in Norway
      analyzes erucic acid and has accumulated extensive data from analyses of fish
      feeds, farmed and wild fish, and seafood products. Our data show that rapeseed
      oil (low erucic acid varieties) and fish oil are the main sources of erucic acid
      in feed for farmed fish. Erucic acid content increases with total fat content,
      both in farmed and wild fish, and it is particularly high in fish liver, fish
      oil, and oily fish, such as mackerel. We show that the current TDI could be
      exceeded with a 200 g meal of mackerel, as at the maximum concentration analyzed,
      such a meal would contribute 143% to the TDI of a 60 kg person. These data cover
      a current knowledge gap in the scientific literature regarding the content of
      erucic acid in fish and seafood.

PMID- 30301172
TI  - A Novel Sampling Method to Measure Socioeconomic Drivers of Aedes Albopictus
      Distribution in Mecklenburg County, North Carolina.
AB  - Climate change, urbanization, and globalization have facilitated the spread of
      Aedes mosquitoes into regions that were previously unsuitable, causing an
      increased threat of arbovirus transmission on a global scale. While numerous
      studies have addressed the urban ecology of Ae. albopictus, few have accounted
      for socioeconomic factors that affect their range in urban regions. Here we
      introduce an original sampling design for Ae. albopictus, that uses a spatial
      optimization process to identify urban collection sites based on both geographic
      parameters as well as the gradient of socioeconomic variables present in
      Mecklenburg County, North Carolina, encompassing the city of Charlotte, a rapidly
      growing urban environment. We collected 3,645 specimens of Ae. albopictus (87% of
      total samples) across 12 weeks at the 90 optimized site locations and modelled
      the relationships between the abundance of gravid Ae. albopictus and a variety of
      neighborhood socioeconomic attributes as well as land cover characteristics. Our
      results demonstrate that the abundance of gravid Ae. albopictus is inversely
      related to the socioeconomic status of the neighborhood and directly related to
      both landscape heterogeneity as well as proportions of particular resident
      races/ethnicities. We present our results alongside a description of our novel
      sampling scheme and its usefulness as an approach to urban vector epidemiology.
      Additionally, we supply recommendations for future investigations into the
      socioeconomic determinants of vector-borne disease risk.

PMID- 30301171
TI  - Clinical Implications of Hepatitis B Virus RNA and Covalently Closed Circular DNA
      in Monitoring Patients with Chronic Hepatitis B Today with a Gaze into the
      Future: The Field Is Unprepared for a Sterilizing Cure.
AB  - . Chronic hepatitis B virus (HBV) infection has long remained a critical global
      health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the
      HBV genome that maintains HBV chronicity. Decades of extensive research resulted
      in the two therapeutic options currently available: nucleot(s)ide analogs and
      interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients
      has been established, including the recently discovered encapsidated pregenomic
      RNA in serum, which can be used to determine treatment end-points and to predict
      the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and
      cccDNA and its epigenetic modifications are associated with the clinical course
      and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new
      antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T
      cell therapies aim at completely eliminating HBV, and it is clear that the
      diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In
      this review, we discuss the currently available tools for detecting and measuring
      HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of
      these markers, and debate needs and goals within the context of the sterilizing
      cure that is soon to come.

PMID- 30301173
TI  - Photo-Crosslinked Polymeric Matrix with Antimicrobial Functions for Excisional
      Wound Healing in Mice.
AB  - Wound infection extends the duration of wound healing and also causes systemic
      infections such as sepsis, and, in severe cases, may lead to death. Early
      prevention of wound infection and its appropriate treatment are important. A
      photoreactive modified gelatin (GE-BTHE) was synthesized by gelatin and a
      conjugate formed from the 3,3',4,4'-benzophenone tetracarboxylic dianhydride
      (BTDA) and the 2-hydroxyethyl methacrylate (HEMA). Herein, we investigated the
      photocurable polymer solution (GE-BTHE mixture) containing GE-BTHE, poly(ethylene
      glycol) diacrylate (PEGDA), chitosan, and methylene blue (MB), with antimicrobial
      functions and photodynamic antimicrobial chemotherapy for wound dressing. This
      photocurable polymer solution was found to have fast film-forming property
      attributed to the photochemical reaction between GE-BTHE and PEGDA, as well as
      the antibacterial activity in vitro attributed to the ingredients of chitosan and
      MB. Our in vivo results also demonstrated that untreated wounds after 3 days had
      the same scab level as the GE-BTHE mixture-treated wounds after 20 s of
      irradiation, which indicates that the irradiated GE-BTHE mixture can be quickly
      transferred into artificial scabs to protect wounds from an infection that can
      serve as a convenient excisional wound dressing with antibacterial efficacy.
      Therefore, it has the potential to treat nonhealing wounds, deep burns, diabetic
      ulcers and a variety of mucosal wounds.

PMID- 30301174
TI  - Sonic Hedgehog Signaling Pathway in Endothelial Progenitor Cell Biology for
      Vascular Medicine.
AB  - The Hedgehog (HH) signaling pathway plays an important role in embryonic and
      postnatal vascular development and in maintaining the homeostasis of organs.
      Under physiological conditions, Sonic Hedgehog (SHH), a secreted protein
      belonging to the HH family, regulates endothelial cell growth, promotes cell
      migration and stimulates the formation of new blood vessels. The present review
      highlights recent advances made in the field of SHH signaling in endothelial
      progenitor cells (EPCs). The canonical and non-canonical SHH signaling pathways
      in EPCs and endothelial cells (ECs) related to homeostasis, SHH signal
      transmission by extracellular vesicles (EVs) or exosomes containing single-strand
      non-coding miRNAs and impaired SHH signaling in cardiovascular diseases are
      discussed. As a promising therapeutic tool, the possibility of using the SHH
      signaling pathway for the activation of EPCs in patients suffering from
      cardiovascular diseases is further explored.

PMID- 30301175
TI  - Simultaneous Enhancement of Mechanical and Magnetic Properties in Extremely-Fine
      Nanograined Ni-P Alloys.
AB  - Exploring structural effects that influence both the mechanics and magnetism in
      nanocrystalline materials, particularly extremely-fine nanograined ones with
      grain sizes down to several nanometers, is of high interest for developing
      multifunctional materials combining superior mechanical and magnetic
      performances. We found in this work that electrodeposited extremely-fine
      nanograined Ni-P alloys exhibit a significant enhancement of magnetization,
      simultaneously along with an increase in hardness, after low-temperature
      annealing. The relaxation of non-equilibrium structures, precipitation of the
      second phase and the segregation of P atoms to grain boundaries (GBs) during
      annealing have then been sequentially evidenced. By systematically comparing the
      variations in macroscopic and microstructural investigation results among several
      Ni-P alloys with different P contents, we suggest that the second phase has
      little effect on magnetization enhancement, and essentially both the structural
      relaxation and GB segregation can play important roles in hardening by governing
      GB stability, and in the improvement of magnetization by enhancing Ni-Ni atom
      exchange interactions.

PMID- 30301176
TI  - Chemical Constituents from the Stems of Tinospora sinensis and Their Bioactivity.
AB  - Fifty-seven compounds were purified from the stems of Tinospora sinensis,
      including three new compounds characterized as a lignan (1), a pyrrole alkaloid
      (11), and a benzenoid (17), respectively. Their structures were elucidated and
      established by various spectroscopic and spectrometric analytical methods. Among
      the isolates, fifteen compounds were examined for their anti-inflammatory
      potential in vitro. The results showed that several compounds displayed moderate
      inhibition of N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)
      induced superoxide anion generation and elastase release.

PMID- 30301177
TI  - Modern Compact Cities: How Much Greenery Do We Need?
AB  - The modern compact city is identified as a high-density and mixed-use pattern.
      Its features are believed to contribute to a form of functional urban design that
      supports sustainability and, restresses, the importance of ecosystem services.
      Urban green space (UGS) plays a vital role in the design and impact on how
      compact cities have developed and triggered a scientific discord on the amount of
      greenery individuals require and to what extent contemporary approaches address
      the question. Research points to at least 9 m2 of green space per individual with
      an ideal UGS value of 50 m2 per capita. An examination on the perception, use,
      quality, accessibility and health risks of urban green and blue spaces is
      explored, alongside the availability of novel UGS and greenery-related approaches
      that investigate compact city design and planning for health and wellbeing. The
      amount of 'green' and relating UGS availability in cities indicates vital
      knowledge modern compact cities must consider.

PMID- 30301178
TI  - Degassing Rhythms and Fluctuations of Geogenic Gases in A Red Wood-Ant Nest and
      in Soil in The Neuwied Basin (East Eifel Volcanic Field, Germany).
AB  - Geochemical tracers of crustal fluids (CO2, He, Rn) provide a useful tool for the
      identification of buried fault structures. We acquired geochemical data during 7
      months of continual sampling to identify causal processes underlying correlations
      between ambient air and degassing patterns of three gases (CO2, He, Rn) in a nest
      of red wood ants (Formica polyctena; "RWA") and the soil at Goloring in the
      Neuwied Basin, a part of the East Eifel Volcanic Field (EEVF). We explored
      whether temporal relations and degassing rhythms in soil and nest gas
      concentrations could be indicators of hidden faults through which the gases
      migrate to the surface from depth. In nest gas, the coupled system of CO2-He and
      He concentrations exceeding atmospheric standards 2-3 fold suggested that RWA
      nests may be biological indicators of hidden degassing faults and fractures at
      small scales. Equivalently periodic degassing infradian rhythms in the RWA nest,
      soil, and three nearby minerals springs suggested NW-SE and NE-SW tectonic
      linkages. Because volcanic activity in the EEVF is dormant, more detailed
      information on the EEVF's tectonic, magmatic, and degassing systems and its
      active tectonic fault zones are needed. Such data could provide additional
      insights into earthquake processes that are related to magmatic processes at the
      lower crust.

PMID- 30301179
TI  - Identifying Risk of Viral Failure in Treated HIV-Infected Patients Using
      Different Measures of Adherence: The Antiretroviral Therapy Cohort Collaboration.
AB  - Adherence to antiretroviral therapy (ART) is critical for successful treatment of
      Human Immunodeficiency Virus (HIV), but comparisons across settings are difficult
      because adherence is measured in different ways. We examined utility of different
      adherence measures for identification of patients at risk of viral failure (VF).
      Eight cohorts in the ART Cohort Collaboration contributed data from pharmacy
      refills or self-report questionnaires collected between 1996 and 2013 (N =
      11689). For pharmacy data (N = 7156), we examined associations of percentage
      adherence during the 1st year of ART with VF (>500 copies/mL) at 1 year. For self
      report data (N = 4533), we examined 28-day adherence with VF based on closest
      viral load measure within 6 months after questionnaire date. Since adherence
      differed markedly by measurement type, we defined different cut-off points for
      pharmacy (lower <45%, medium 45-99%, higher 100%) and self-report (lower <=95%,
      medium 96-99%, higher 100%) data. Adjusted odds ratios (ORs) for VF in lower and
      medium, compared to higher adherence groups, were 23.04 (95% CI: 18.44-28.78) and
      3.84 (3.36-4.39) for pharmacy data. For self-report data, they were 3.19 (2.31
      4.40) and 1.08 (0.80-1.46). Both types of measure were strongly associated with
      VF. Although adherence measurements over longer time-frames are preferable for
      prediction, they are less useful for intervention.

PMID- 30301180
TI  - Antibacterial and Antibiofilm Activity and Mode of Action of Magainin 2 against
      Drug-Resistant Acinetobacter baumannii.
AB  - Antimicrobial peptides (AMPs) are promising therapeutic agents for treating
      antibiotic-resistant bacterial infections. Previous studies showed that magainin
      2 (isolated from African clawed fogs Xenopus laevis) has antimicrobial activity
      against gram-positive and gram-negative bacteria. The present study was conducted
      to investigate the antibacterial activity of magainin 2 against Acinetobacter
      baumannii. Magainin 2 showed excellent antibacterial activity against A.
      baumannii strains and high stability at physiological salt concentrations. This
      peptide was not cytotoxic towards HaCaT cells and showed no hemolytic activity.
      Biofilm inhibition and elimination were significantly induced in all A. baumannii
      strains exposed to magainin 2. We confirmed the mechanism of magainin 2 on the
      bacterial outer and inner membranes. Collectively, these results suggest that
      magainin 2 is an effective antimicrobial and antibiofilm agent against A.
      baumannii strains.

PMID- 30301181
TI  - Enhanced Gas-Sensing Performance of GO/TiO2 Composite by Photocatalysis.
AB  - Few studies have investigated the gas-sensing properties of graphene
      oxide/titanium dioxide (GO/TiO2) composite combined with photocatalytic effect.
      Room temperature gas-sensing properties of the GO/TiO2 composite were
      investigated towards various reducing gases. The composite sensor showed an
      enhanced gas response and a faster recovery time than a pure GO sensor due to the
      synergistic effect of the hybridization, such as creation of a hetero-junction at
      the interface and modulation of charge carrier density. However, the issue of
      long-term stability at room temperature still remains unsolved even after
      construction of a composite structure. To address this issue, the surface and
      hetero-junction of the GO/TiO2 composite were engineered via a UV process. A
      photocatalytic effect of TiO2 induced the reduction of the GO phase in the
      composite solution. The comparison of gas-sensing properties before and after the
      UV process clearly showed the transition from n-type to p-type gas-sensing
      behavior toward reducing gases. This transition revealed that the dominant
      sensing material is GO, and TiO2 enhanced the gas reaction by providing more
      reactive sites. With a UV-treated composite sensor, the function of identifying
      target gas was maintained over a one-month period, showing strong resistance to
      humidity.

PMID- 30301182
TI  - Application of Neurokinin-1 Receptor in Targeted Strategies for Glioma Treatment.
      Part I: Synthesis and Evaluation of Substance P Fragments Labeled with 99mTc and
      177Lu as Potential Receptor Radiopharmaceuticals.
AB  - Gliomas, particularly WHO grade IV glioblastoma multiforme, are one of the most
      common and aggressive primary tumors of the central nervous system. The
      neuropeptide, substance P (SP), is the physiological ligand of the neurokinin-1
      (NK-1) receptor that is consistently overexpressed in glioblastoma cells. The aim
      of this work was to study physico-chemical and biological properties of different
      SP analogues labeled with technetium-99m and lutetium-177 radionuclides. The
      synthesized compounds were characterized in vitro by partition coefficients
      (logP) and their stability was investigated in various physiological solutions.
      Biological properties (Kd, Bmax) were characterized using the U373 MG cell line.
      The obtained lipophilicity values of the [99mTc]NS3/CN-SP and [177Lu]DOTA-SP
      radiobioconjugates were in the range of -0.3 to +0.6 and -2.5 to -5.0,
      respectively. The studied radiobioconjugates were stable in PBS buffer and CSF,
      as well as in 10 mM histidine and/or cysteine solutions whereas in human serum
      showed enzymatic biodegradation. [177Lu]DOTA-[Thi8,Met(O2)11]SP(1-11),
      [177Lu]DOTA-SP(4-11) and [177Lu]DOTA-[Thi8,Met(O2)11]SP(5-11) radiobioconjugates
      bound specifically to NK-1 receptors expressed on glioblastoma cells with
      affinity in the nanomolar range. To conclude, the shorter analogues of SP can be
      used as vectors, nevertheless they still do not fulfil all requirements for
      preparations in nuclear medicine.

PMID- 30301183
TI  - Nanostructured TiO2 Carbon Paste Based Sensor for Determination of Methyldopa.
AB  - Methyldopa is a catecholamine widely used in the treatment of mild to moderate
      hypertension whose determination in pharmaceutical formulae is of upmost
      importance for dose precision. Henceforth, a low-cost carbon paste electrode
      (CPE) consisting of graphite powder obtained from a crushed pencil stick was
      herein modified with nanostructured TiO2 (TiO2@CPE) aiming for the detection of
      methyldopa in pharmaceutical samples. The TiO2-modified graphite powder was
      characterized by scanning electron microscopy and X-ray diffraction, which
      demonstrated the oxide nanostructured morphology. Results evidenced that
      sensitivity was nonetheless increased due to electro-catalytic effects promoted
      by metal modification, and linear response obtained by differential pulse
      voltammetry for the determination of methyldopa (pH = 5.0) was between 10-180
      MUmol/L (Limit of Detection = 1 MUmol/L) with the TiO2@CPE sensor. Furthermore,
      the constructed sensor was successfully applied in the detection of methyldopa in
      pharmaceutical formulations and excipients promoted no interference, that
      indicates that the sensor herein developed is a cheap, reliable, and useful
      strategy to detect methyldopa in pharmaceutical samples, and may also be
      applicable in determinations of similar compounds.

PMID- 30301184
TI  - The Significance of Low Titre Antigliadin Antibodies in the Diagnosis of Gluten
      Ataxia.
AB  - BACKGROUND: Patients with gluten ataxia (GA) without enteropathy have lower
      levels of antigliadin antibodies (AGA) compared to patients with coeliac disease
      (CD). Magnetic Resonance Spectroscopy (NAA/Cr area ratio) of the cerebellum
      improves in patients with GA following a strict gluten-free diet (GFD). This is
      associated with clinical improvement. We present our experience of the effect of
      a GFD in patients with ataxia and low levels of AGA antibodies measured by a
      commercial assay. METHODS: Consecutive patients with ataxia and serum AGA levels
      below the positive cut-off for CD but above a re-defined cut-off in the context
      of GA underwent MR spectroscopy at baseline and after a GFD. RESULTS: Twenty-one
      consecutive patients with GA were included. Ten were on a strict GFD with
      elimination of AGA, 5 were on a GFD but continued to have AGA, and 6 patients did
      not go on a GFD. The NAA/Cr area ratio from the cerebellar vermis increased in
      all patients on a strict GFD, increased in only 1 out of 5 (20%) patients on a
      GFD with persisting circulating AGA, and decreased in all patients not on a GFD.
      CONCLUSION: Patients with ataxia and low titres of AGA benefit from a strict GFD.
      The results suggest an urgent need to redefine the serological cut-off for
      circulating AGA in diagnosing GA.

PMID- 30301185
TI  - Role of Milk-Derived Antibacterial Peptides in Modern Food Biotechnology: Their
      Synthesis, Applications and Future Perspectives.
AB  - Milk-derived antibacterial peptides (ABPs) are protein fragments with a positive
      influence on the functions and conditions of a living organism. Milk-derived ABPs
      have several useful properties important for human health, comprising a
      significant antibacterial effect against various pathogens, but contain toxic
      side-effects. These compounds are mainly produced from milk proteins via
      fermentation and protein hydrolysis. However, they can also be produced using
      recombinant DNA techniques or organic synthesis. This review describes the role
      of milk-derived ABPs in modern food biotechnology with an emphasis on their
      synthesis and applications. Additionally, we also discuss the mechanisms of
      action and the main bioproperties of ABPs. Finally, we explore future
      perspectives for improving ABP physicochemical properties and diminishing their
      toxic side-effects.

PMID- 30301186
TI  - Design of an Aluminum/Polymer Plasmonic 2D Crystal for Label-Free Optical
      Biosensing.
AB  - A design study of a nanostructured two-dimensional plasmonic crystal based on
      aluminum and polymeric material for label-free optical biosensing is presented.
      The structure is formed of Al nanohole and nanodisk array layers physically
      separated by a polymeric film. The photonic configuration was analyzed through
      finite-difference time-domain (FDTD) simulations. The calculated spectral
      reflectance of the device exhibits a surface plasmon polariton (SPP) resonance
      feature sensitive to the presence of a modeled biolayer adhered onto the metal
      surfaces. Simulations also reveal that the Al disks suppress an undesired SPP
      resonance, improving the device performance in terms of resolution as compared to
      that of a similar configuration without Al disks. On the basis of
      manufacturability issues, nanohole diameter and depth were considered as design
      parameters, and a multi-objective optimization process was employed to determine
      the optimum dimensional values from both performance and fabrication points of
      view. The effect of Al oxidation, which is expected to occur in an actual device,
      was also studied.

PMID- 30301187
TI  - Audencel Immunotherapy Based on Dendritic Cells Has No Effect on Overall and
      Progression-Free Survival in Newly Diagnosed Glioblastoma: A Phase II Randomized
      Trial.
AB  - Dendritic cells (DCs) are antigen-presenting cells that are capable of priming
      anti-tumor immune responses, thus serving as attractive tools to generate tumor
      vaccines. In this multicentric randomized open-label phase II study, we
      investigated the efficacy of vaccination with tumor lysate-charged autologous DCs
      (Audencel) in newly diagnosed glioblastoma multiforme (GBM). Patients aged 18 to
      70 years with histologically proven primary GBM and resection of at least 70%
      were randomized 1:1 to standard of care (SOC) or SOC plus vaccination (weekly
      intranodal application in weeks seven to 10, followed by monthly intervals). The
      primary endpoint was progression-free survival at 12 months. Secondary endpoints
      were overall survival, safety, and toxicity. Seventy-six adult patients were
      analyzed in this study. Vaccinations were given for seven (3-20) months on
      average. No severe toxicity was attributable to vaccination. Seven patients
      showed flu-like symptoms, and six patients developed local skin reactions.
      Progression-free survival at 12 months did not differ significantly between the
      control and vaccine groups (28.4% versus 24.5%, p = 0.9975). Median overall
      survival was similar with 18.3 months (vaccine: 564 days, 95% CI: 436-671 versus
      control: 568 days, 95% CI: 349-680; p = 0.89, harzard ratio (HR) 0.99). Hence, in
      this trial, the clinical outcomes of patients with primary GBM could not be
      improved by the addition of Audencel to SOC.

PMID- 30301188
TI  - Effect of Resveratrol on Reactive Oxygen Species-Induced Cognitive Impairment in
      Rats with Angiotensin II-Induced Early Alzheimer's Disease ?.
AB  - Recent studies have indicated that several anti-hypertensive drugs may delay the
      development and progression of Alzheimer's disease (AD). However, the
      relationships among AD, hypertension, and oxidative stress remain to be
      elucidated. Here, we aimed to determine whether reactive oxygen species (ROS)
      reduction by resveratrol in the brain leads to cognitive impairment reduction in
      rats with angiotensin II (Ang-II)-induced early AD. Male Wistar Kyoto (WKY) rats
      with Ang-II-induced AD were treated with losartan or resveratrol for two weeks.
      Our results show decreased blood pressure, increased hippocampal brain-derived
      neurotrophic factor (BDNF) level, and decreased nucleus tractus solitarius (NTS)
      ROS production in the Ang-II groups with losartan (10 mg/kg), or resveratrol (10
      mg/kg/day) treatment. Furthermore, losartan inhibition of hippocampal TauT231
      phosphorylation activated AktS473 phosphorylation, and significantly abolished
      Ang-II-induced Abeta precursors, active caspase 3, and glycogen synthase kinase
      3beta (GSK-3beta)Y216 expressions. Consistently, resveratrol showed similar
      effects compared to losartan. Both losartan and resveratrol restored hippocampal
      dependent contextual memory by NADPH oxidase 2 (NOX2) deletion and superoxide
      dismutase 2 (SOD2) elevation. Our results suggest that both losartan and
      resveratrol exert neuroprotective effects against memory impairment and
      hippocampal damage by oxidative stress reduction in early stage AD rat model.
      These novel findings indicate that resveratrol may represent a pharmacological
      option similar to losartan for patients with hypertension at risk of AD during
      old age.

PMID- 30301190
TI  - Variations in Physiology and Multiple Bioactive Constituents under Salt Stress
      Provide Insight into the Quality Evaluation of Apocyni Veneti Folium.
AB  - As one of the major abiotic stresses, salinity stress may affect the physiology
      and biochemical components of Apocynum venetum L. To systematically evaluate the
      quality of Apocyni Veneti Folium (AVF) from the perspective of physiological and
      the wide variety of bioactive components response to various concentrations of
      salt stress, this experiment was arranged on the basis of ultra-fast liquid
      chromatography tandem triple quadrupole mass spectrometry (UFLC-QTRAP-MS/MS)
      technology and multivariate statistical analysis. Physiological characteristics
      of photosynthetic pigments, osmotic homeostasis, lipid peroxidation product, and
      antioxidative enzymes were introduced to investigate the salt tolerance mechanism
      of AVF under salinity treatments of four concentrations (0, 100, 200, and 300 mM
      NaCl, respectively). Furthermore, a total of 43 bioactive constituents, including
      14 amino acids, nine nucleosides, six organic acids, and 14 flavonoids were
      quantified in AVF under salt stress. In addition, multivariate statistical
      analysis, including hierarchical clustering analysis, principal component
      analysis (PCA), and gray relational analysis (GRA) was employed to systematically
      cluster, distinguish, and evaluate the samples, respectively. Compared with the
      control, the results demonstrated that 200 mM and 100 mM salt stress contributed
      to maintain high quality of photosynthesis, osmotic balance, antioxidant enzyme
      activity, and the accumulation of metabolites, except for total organic acids,
      and the quality of AVF obtained by these two groups was better than others;
      however, under severe stress, the accumulation of the oxidative damage and the
      reduction of metabolite caused by inefficiently scavenging reactive oxygen
      species (ROS) lead to lower quality. In summary, the proposed method may provide
      integrated information for the quality evaluation of AVF and other salt-tolerant
      Chinese medicines.

PMID- 30301189
TI  - Genome-Wide Investigation of Genes Regulated by ERalpha in Breast Cancer Cells.
AB  - Estrogen receptor alpha (ERalpha), which has been detected in over 70% of breast
      cancer cases, is a driving factor for breast cancer growth. For investigating the
      underlying genes and networks regulated by ERalpha in breast cancer, RNA-seq was
      performed between ERalpha transgenic MDA-MB-231 cells and wild type MDA-MB-231
      cells. A total of 267 differentially expressed genes (DEGs) were identified. Then
      bioinformatics analyses were performed to illustrate the mechanism of ERalpha.
      Besides, by comparison of RNA-seq data obtained from MDA-MB-231 cells and
      microarray dataset obtained from estrogen (E2) stimulated MCF-7 cells, an overlap
      of 126 DEGs was screened. The expression level of ERalpha was negatively
      associated with metastasis and EMT in breast cancer. We further verified that
      ERalpha might inhibit metastasis by regulating of VCL and TNFRSF12A, and suppress
      EMT by the regulating of JUNB and ID3. And the relationship between ERalpha and
      these genes were validated by RT-PCR and correlation analysis based on TCGA
      database. By PPI network analysis, we identified TOP5 hub genes, FOS, SP1,
      CDKN1A, CALCR and JUNB, which were involved in cell proliferation and invasion.
      Taken together, the whole-genome insights carried in this work can help fully
      understanding biological roles of ERalpha in breast cancer.

PMID- 30301192
TI  - A Robotic Context Query-Processing Framework Based on Spatio-Temporal Context
      Ontology.
AB  - Service robots operating in indoor environments should recognize dynamic changes
      from sensors, such as RGB-depth (RGB-D) cameras, and recall the past context.
      Therefore, we propose a context query-processing framework, comprising spatio
      temporal robotic context query language (ST-RCQL) and a spatio-temporal robotic
      context query-processing system (ST-RCQP), for service robots. We designed them
      based on spatio-temporal context ontology. ST-RCQL can query not only the current
      context knowledge, but also the past. In addition, ST-RCQL includes a variety of
      time operators and time constants; thus, queries can be written very efficiently.
      The ST-RCQP is a query-processing system equipped with a perception handler,
      working memory, and backward reasoner for real-time query-processing. Moreover,
      ST-RCQP accelerates query-processing speed by building a spatio-temporal index in
      the working memory, where percepts are stored. Through various qualitative and
      quantitative experiments, we demonstrate the high efficiency and performance of
      the proposed context query-processing framework.

PMID- 30301191
TI  - Secondary Unconjugated Bile Acids Induce Hepatic Stellate Cell Activation.
AB  - Hepatic stellate cells (HSCs) are key players in liver fibrosis, cellular
      senescence, and hepatic carcinogenesis. Bile acids (BAs) are involved in the
      activation of HSCs, but the detailed mechanism of this process remains unclear.
      We conducted a comprehensive DNA microarray study of the human HSC line LX-2
      treated with deoxycholic acid (DCA), a secondary unconjugated BA. Additionally,
      LX-2 cells were exposed to nine BAs and studied using immunofluorescence
      staining, enzyme-linked immunosorbent assay, and flow cytometry to examine the
      mechanisms of HSC activation. We focused on the tumor necrosis factor (TNF)
      pathway and revealed upregulation of genes related to nuclear factor kappa B (NF
      kappaB) signaling and senescence-associated secretory phenotype factors. alpha
      Smooth muscle actin (alpha-SMA) was highly expressed in cells treated with
      secondary unconjugated BAs, including DCA, and a morphological change associated
      with radial extension of subendothelial protrusion was observed. Interleukin-6
      level in culture supernatant was significantly higher in cells treated with
      secondary unconjugated BAs. Flow cytometry showed that the proportion of cells
      highly expressing alpha-SMA was significantly increased in HSCs cultured with
      secondary unconjugated BAs. We demonstrated that secondary unconjugated BAs
      induced the activation of human HSCs.

PMID- 30301193
TI  - Efficient Encapsulation of Citral in Fast-Dissolving Polymer-Free Electrospun
      Nanofibers of Cyclodextrin Inclusion Complexes: High Thermal Stability, Longer
      Shelf-Life, and Enhanced Water Solubility of Citral.
AB  - Here, we report a facile production of citral/cyclodextrin (CD) inclusion complex
      (IC) nanofibers (NFs) from three types of CDs (hydroxypropyl-beta-cyclodextrin
      (HPbetaCD), hydroxypropyl-gamma-cyclodextrin (HPgammaCD), and methylated-beta
      cyclodextrin (MbetaCD)) by an electrospinning technique without the need of any
      polymeric carrier matrix. Self-standing nanofibrous webs of citral/CD-IC
      nanofibers (citral/CD-IC-NF) with uniform fiber morphology have been successfully
      electrospun from aqueous solutions of citral/CD-IC. Thanks to the inclusion
      complex formed with CDs, the efficient preservation of citral (up to ~80%) in
      citral/CD-IC-NFs was observed. In addition, the citral/CD-IC-NFs have shown ~50%
      preservation of citral for 15 days at room temperature even though citral has a
      highly volatile nature. The enhanced thermal stability of citral (~100-300
      degrees C) in citral/CD-IC-NFs compared to pure citral (~50-165 degrees C) has
      been observed. Moreover, citral/CD-IC-NFs tended to disintegrate in water very
      quickly. To summarize, citral was efficiently encapsulated in citral/CD-IC-NFs,
      and these citral/CD-IC-NFs have been shown to be fast dissolving. In citral/CD-IC
      NFs, citral/CD-ICs have enhanced water solubility of citral along with high
      temperature stability and a longer shelf-life.

PMID- 30301196
TI  - SECOND: Sparsely Embedded Convolutional Detection.
AB  - LiDAR-based or RGB-D-based object detection is used in numerous applications,
      ranging from autonomous driving to robot vision. Voxel-based 3D convolutional
      networks have been used for some time to enhance the retention of information
      when processing point cloud LiDAR data. However, problems remain, including a
      slow inference speed and low orientation estimation performance. We therefore
      investigate an improved sparse convolution method for such networks, which
      significantly increases the speed of both training and inference. We also
      introduce a new form of angle loss regression to improve the orientation
      estimation performance and a new data augmentation approach that can enhance the
      convergence speed and performance. The proposed network produces state-of-the-art
      results on the KITTI 3D object detection benchmarks while maintaining a fast
      inference speed.

PMID- 30301194
TI  - Headache Associated with Coeliac Disease: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: The aim of this systematic review was to explore the relationship
      between coeliac disease (CD) and headache. The objectives were to establish the
      prevalence of each entity amongst the other, to explore the role of gluten free
      diet (GFD), and to describe the imaging findings in those affected by headaches
      associated with CD. METHODOLOGY: A systematic computer-based literature search
      was conducted on the PubMed database. Information regarding study type,
      population size, the age group included, prevalence of CD amongst those with
      headache and vice versa, imaging results, the nature of headache, and response to
      GFD. RESULTS: In total, 40 articles published between 1987 and 2017 qualified for
      inclusion in this review. The mean pooled prevalence of headache amongst those
      with CD was 26% (95% CI 19.5-33.9%) in adult populations and 18.3% (95% CI 10.4
      30.2%) in paediatric populations. The headaches are most often migraine-like. In
      children with idiopathic headache, the prevalence of CD is 2.4% (95% CI 1.5
      3.7%), whereas data for adult populations is presently unavailable. Brain imaging
      can be normal, although, cerebral calcifications on CT, white matter
      abnormalities on MRI and deranged regional cerebral blood flow on SPECT can be
      present. GFD appears to be an effective management for headache in the context of
      CD, leading to total resolution of headaches in up to 75% of patients.
      CONCLUSIONS: There is an increased prevalence of CD amongst idiopathic headache
      and vice versa. Therefore, patients with headache of unknown origin should be
      screened for CD, as such patients may symptomatically benefit from a GFD.

PMID- 30301195
TI  - Do the Effects of Resveratrol on Thermogenic and Oxidative Capacities in IBAT and
      Skeletal Muscle Depend on Feeding Conditions?
AB  - The aim of this study was to compare the effects of mild energy restriction and
      resveratrol on thermogenic and oxidative capacity in interscapular brown adipose
      tissue (IBAT) and in skeletal muscle. Rats were fed a high-fat high-sucrose diet
      for six weeks, and divided into four experimental groups fed a standard diet: a
      control group, a resveratrol-treated group, an energy-restricted group and an
      energy-restricted group treated with resveratrol. Weights of IBAT, gastrocnemius
      muscle and fat depots were measured. Activities of carnitine palmitoyltransferase
      (CPT) and citrate synthase (CS), protein levels of sirtuin (SIRT1 and 3),
      uncoupling proteins (UCP1 and 3), glucose transporter (GLUT4), mitochondrial
      transcription factor (TFAM), nuclear respiratory factor (NRF1), peroxisome
      proliferator-activated receptor (PPARalpha) and AMP activated protein kinase
      (AMPK) and peroxisome proliferator-activated receptor gamma coactivator
      (PGC1alpha) activation were measured. No changes in IBAT and gastrocnemius
      weights were found. Energy-restriction, but not resveratrol, decreased the
      weights of adipose depots. In IBAT, resveratrol enhanced thermogenesis activating
      the SIRT1/PGC1alpha/PPARalpha axis. Resveratrol also induced fatty acid oxidation
      and glucose uptake. These effects were similar when resveratrol was combined with
      energy restriction. In the case of gastrocnemius muscle, the effects were not as
      clear as in the case of IBAT. In this tissue, resveratrol increased oxidative
      capacity. The combination of resveratrol and energy restriction seemingly did not
      improve the effects induced by the polyphenol alone.

PMID- 30301197
TI  - Further Evidence on Efficacy of Diet Supplementation with Fatty Acids in Ocular
      Pathologies: Insights from the EAE Model of Optic Neuritis.
AB  - In the experimental autoimmune encephalomyelitis (EAE) mouse model of optic
      neuritis, we recently demonstrated that diet supplementation with a balanced
      mixture of fatty acids (FAs), including omega 3 and omega 6, efficiently limited
      inflammatory events in the retina and prevented retinal ganglion cell (RGC)
      death, although mechanisms underlying the efficacy of FAs were to be elucidated.
      Whether FAs effectiveness was accompanied by efficient rescue of demyelinating
      events in the optic nerve was also unresolved. Finally, the possibility that RGC
      rescue might result in ameliorated visual performance remained to be
      investigated. Here, the EAE model of optic neuritis was used to investigate
      mechanisms underlying the anti-inflammatory effects of FAs, including their
      potential efficacy on macrophage polarization. In addition, we determined how FAs
      induced rescue of RGC degeneration was related to optic nerve histopathology by
      performing ultrastructural morphometric analysis with transmission electron
      microscopy. Finally, RGC rescue was correlated with visual performance by
      recording photopic electroretinogram, an efficient methodology to unravel the
      role of RGCs in the generation of electroretinographic waves. We conclude that
      the ameliorative effects of FAs were dependent on a predominant anti-inflammatory
      action including a role on promoting the shift of macrophages from the
      inflammatory M1 phenotype towards the anti-inflammatory M2 phenotype. This would
      finally result in restored optic nerve histopathology and ameliorated visual
      performance. These findings can now offer new perspectives for implementing our
      knowledge on the effectiveness of diet supplementation in counteracting optic
      neuritis and suggest the importance of FAs as possible adjuvants in therapies
      against inflammatory diseases of the eye.

PMID- 30301199
TI  - Direct Depth SLAM: Sparse Geometric Feature Enhanced Direct Depth SLAM System for
      Low-Texture Environments.
AB  - This paper presents a real-time, robust and low-drift depth-only SLAM
      (simultaneous localization and mapping) method for depth cameras by utilizing
      both dense range flow and sparse geometry features from sequential depth images.
      The proposed method is mainly composed of three optimization layers, namely
      Direct Depth layer, ICP (iterative closet point) Refined layer and Graph
      Optimization layer. The Direct Depth layer uses a range flow constraint equation
      to solve the fast 6-DOF (six degrees of freedom) frame-to-frame pose estimation
      problem. Then, the ICP Refined layer is used to reduce the local drift by
      applying local map based motion estimation strategy. After that, we propose a
      loop closure detection algorithm by extracting and matching sparse geometric
      features and construct a pose graph for the purpose of global pose optimization.
      We evaluate the performance of our method using benchmark datasets and real scene
      data. Experiment results show that our front-end algorithm clearly over performs
      the classic methods and our back-end algorithm is robust to find loop closures
      and reduce the global drift.

PMID- 30301200
TI  - Engineering of an Anti-Inflammatory Peptide Based on the Disulfide-Rich
      Linaclotide Scaffold.
AB  - Inflammatory bowel diseases are a set of complex and debilitating diseases, for
      which there is no satisfactory treatment. Peptides as small as three amino acids
      have been shown to have anti-inflammatory activity in mouse models of colitis,
      but they are likely to be unstable, limiting their development as drug leads.
      Here, we have grafted a tripeptide from the annexin A1 protein into linaclotide,
      a 14-amino-acid peptide with three disulfide bonds, which is currently in
      clinical use for patients with chronic constipation or irritable bowel syndrome.
      This engineered disulfide-rich peptide maintained the overall fold of the
      original synthetic guanylate cyclase C agonist peptide, and reduced inflammation
      in a mouse model of acute colitis. This is the first study to show that this
      disulfide-rich peptide can be used as a scaffold to confer a new bioactivity.

PMID- 30301198
TI  - Can Nuts Mitigate Malnutrition in Older Adults? A Conceptual Framework.
AB  - The proportion of adults aged over 60 years in the world is expected to reach 20%
      by the year 2050. Ageing is associated with several physiological changes that
      increase the risk of malnutrition among this population. Malnutrition is
      characterized by deficiencies or insufficiencies of macro- and micronutrients.
      Malnutrition has detrimental effects on the health, wellbeing, and quality of
      life in older adults. Nuts are rich in energy, unsaturated fats, and protein, as
      well as other nutrients that provide a range of health benefits. While the
      effects of nuts on overnutrition have been studied extensively, very few studies
      have been specifically designed to understand the role of nuts in mitigating
      undernutrition in the elderly. Therefore, this review explores the potential role
      of nuts in improving the nutritional status of older adults who are at risk of
      undernutrition. Several properties of whole nuts, some of which appear important
      for addressing overnutrition, (e.g., hardness, lower-than-expected nutrient
      availability, satiety-enhancing effects) may limit their effectiveness as a food
      to combat undernutrition. However, we propose that modifications such as
      transforming the physical form of nuts, addressing the timing of nut ingestion,
      and introducing variety may overcome these barriers. This review also discusses
      the feasibility of using nuts to prevent and reverse undernutrition among older
      adults. We conclude with a recommendation to conduct clinical studies in the
      future to test this conceptual framework.

PMID- 30301202
TI  - Sensing and Reliability Improvement of Electrostatic-Discharge Transient by
      Discrete Engineering for High-Voltage 60-V n-Channel Lateral-Diffused MOSFETs
      with Embedded Silicon-Controlled Rectifiers.
AB  - High-voltage n-channel lateral-diffused metal-oxide-semiconductor field-effect
      transistor (nLDMOS) components, fabricated by a TSMC 0.25-m 60-V bipolar-CMOS
      DMOS (BCD) process with drain-side embedded silicon-controlled rectifier (SCR) of
      the n-p-n-arranged and p-n-p-arranged types, were investigated, in order to
      determine the devices' electrostatic discharge (ESD)-sensing behavior and
      capability by discrete anode engineering. As for the drain-side n-p-n-arranged
      type with discrete-anode manners, transmission-line-pulse (TLP) testing results
      showed that the ESD ability (It2 value) was slightly upgraded. When the discrete
      physical parameter was 91 rows, the optimal It2 reached 2.157 A (increasing 17.7%
      compared with the reference sample). On the other hand, the drain-side SCR p-n-p
      arranged type with discrete-anode manner had excellent SCR behavior, and its It2
      values could be increased to >7 A (increasing >281.9% compared with the reference
      DUT). Moreover, under discrete anode engineering, the drain-side SCR n-p-n
      arranged and p-n-p-arranged types had clearly higher ESD ability, except for the
      few discrete physical parameters. Therefore, using the anode discrete
      engineering, the ESD dissipation ability of a high-voltage (HV) nLDMOS with drain
      side SCRs will have greater effectiveness.

PMID- 30301203
TI  - Exploring Morphine-Triggered PKC-Targets and Their Interaction with Signaling
      Pathways Leading to Pain via TrkA.
AB  - It is well accepted that treatment of chronic pain with morphine leads to MU
      opioid receptor (MOR) desensitization and the development of morphine tolerance.
      MOR activation by the selective peptide agonist, D-Ala2, N-MePhe4, Gly-ol]
      enkephalin(DAMGO), leads to robust G protein receptor kinase activation, beta
      arrestin recruitment, and subsequent receptor endocytosis, which does not occur
      in an activation by morphine. However, MOR activation by morphine induces
      receptor desensitization, in a Protein kinase C (PKC) dependent manner. PKC
      inhibitors have been reported to decrease receptor desensitization, reduce opiate
      tolerance, and increase analgesia. However, the exact role of PKC in these
      processes is not clearly delineated. The difficulties in establishing a
      particular role for PKC have been, in part, due to the lack of reagents that
      allow the selective identification of PKC targets. Recently, we generated a
      conformation state-specific anti-PKC antibody that preferentially recognizes the
      active state of this kinase. Using this antibody to selectively isolate PKC
      substrates and a proteomics strategy to establish the identity of the proteins,
      we examined the effect of morphine treatment on the PKC targets. We found an
      enhanced interaction of a number of proteins with active PKC, in the presence of
      morphine. In this article, we discuss the role of these proteins in PKC-mediated
      MOR desensitization and analgesia. In addition, we posit a role for some of these
      proteins in mediating pain by TrKA activation, via the activation of transient
      receptor potential cation channel subfamily V member 1 (TRPV1). Finally, we
      discuss how these new PKC interacting proteins and pathways could be targeted for
      the treatment of pain.

PMID- 30301201
TI  - Epidemiology and Elimination of HCV-Related Liver Disease.
AB  - Hepatitis C virus (HCV) infection, defined by active carriage of HCV RNA, affects
      nearly 1.0% of the worldwide population. The main risk factors include unsafe
      injection drug use and iatrogenic infections. Chronic HCV infection can promote
      liver damage, cirrhosis and hepatocellular carcinoma (HCC) in affected
      individuals. The advent of new second-generation, direct-acting antiviral (DAA)
      agents allow a virological cure in more than 90% of treated patients, and
      therefore prevent HCV-related complications. Recently, concerns have been raised
      regarding the safety of DAA-regimens in cirrhotic patients with respect to the
      occurrence and the recurrence of HCC. Here, we review the current available data
      on HCV epidemiology, the beneficial effects of therapy, and discuss the recent
      controversy with respect to the potential link with liver cancer. We also
      highlight the challenges that have to be overcome to achieve the ambitious World
      Health Organization objective of HCV eradication by 2030.

PMID- 30301204
TI  - Aqueous Extract of Davallia mariesii Attenuates 6-Hydroxydopamine-Induced
      Oxidative Damage and Apoptosis in B35 Cells Through Inhibition of Caspase Cascade
      and Activation of PI3K/AKT/GSK-3beta Pathway.
AB  - The medicinal ferns of Polydiaceae and Davalliaceae species are called "Gusuibu"
      by Chinese physicians and used as antiaging dietary medicines. Our previous
      report revealed that Drynaria fortunei (Polydiaceae) protected against 6
      hydroxydopamine (6-OHDA)-induced oxidative damage via the PI3K/AKT pathway in B35
      neuroblastoma cells. The present study compares the antioxidant phytoconstituent
      contents and radical scavenging capacities of five Davalliaceae species. The
      further aim was to clarify the protective mechanism of Davallia mariesii (DM)
      against 6-OHDA-induced oxidative damage and apoptosis in B35 cells. The results
      show that Araiostegia perdurans (AP) and DM extracts have better radical
      scavenging capacities against 1,1-diphenyl-2-picryhydrazyl (DPPH) and reactive
      oxygen species (ROS) than other Davalliaceae species. However, only DM extract
      inhibited 6-OHDA autoxidation under cell-free systems and increased cell
      viability, compared to B35 cells solely exposed to 6-OHDA. DM extract decreased
      apoptosis and restored mitochondrial expression in 6-OHDA-treated B35 cells.
      Additional data indicated that DM extract decreased intracellular ROS and nitric
      oxide levels generated by 6-OHDA exposure. DM extract also restored glutathione
      (GSH) levels and the activities of glutathione peroxidase and reductase, and then
      decreased the elevated malondialdehyde (MDA) levels. Finally, DM extract
      regulated the protein expression of the caspase cascade and PI3K/AKT/GSK-3beta
      pathways. These results suggest that the protective mechanism of DM extract
      against 6-OHDA-induced oxidative damage and apoptosis might be related to its
      radical scavenging capacity, maintaining the mitochondrial function to inhibit
      the Bcl-2/caspase cascade pathway and activating intracellular antioxidant
      defenses (GSH recycling, HO-1 and NQO-1) by modulating the activation of the
      PI3K/AKT/GSK-3beta pathway.

PMID- 30301206
TI  - Effects of Low Pressure Treatment on the Mortality of Different Life Stages of
      Indianmeal moth (Plodia interpunctella) and the Quality of Dried Chinese Jujube.
AB  - Low pressure technology is a potential non-chemical method to control insects in
      agriculture products. The purpose of this study was to determine the tolerance of
      different life stages of indianmeal moth (Plodia interpunctella) to low pressure
      and to validate the mortality of P. interpunctella when infesting Chinese jujube
      (Zizyphus jujuba Miller) using a low pressure system. Results showed that larvae
      were the most tolerant life stage of P. interpunctella, with a minimum exposure
      time of 41.4 h at 1.3 kPa and 25  degrees C to obtain 100% mortality. Pupae were
      the most susceptible life stage, with a lethal time of 12 h under the above low
      pressure conditions. The survival ratio of P. interpunctella in jujube decreased
      with increasing exposure time and reached 0% when the jujubes with P.
      interpunctella larvae were exposed to low-pressure treatment for 41.6 h at 1.3
      kPa and 25  degrees C. Although the color, moisture, soluble solid, and vitamin C
      contents were slightly changed, there was no significant quality difference in
      these factors between control and treated jujubes. The information provided by
      this study is useful in developing effective non-chemical low-pressure treatments
      for disinfesting agricultural products.

PMID- 30301205
TI  - Intestinal Saturated Long-Chain Fatty Acid, Glucose and Fructose Transporters and
      Their Inhibition by Natural Plant Extracts in Caco-2 Cells.
AB  - The intestinal absorption of fatty acids, glucose and fructose is part of the
      basic requirements for the provision of energy in the body. High access of
      saturated longchain fatty acids (LCFA), glucose and fructose can facilitate the
      development of metabolic diseases, particularly the metabolic syndrome and type-2
      diabetes mellitus (T2DM). Research has been done to find substances which
      decelerate or inhibit intestinal resorption of these specific food components.
      Promising targets are the inhibition of intestinal long-chain fatty acid (FATP2,
      FATP4), glucose (SGLT1, GLUT2) and fructose (GLUT2, GLUT5) transporters by plant
      extracts and by pure substances. The largest part of active components in plant
      extracts belongs to the group of polyphenols. This review summarizes the
      knowledge about binding sites of named transporters and lists the plant extracts
      which were tested in Caco-2 cells regarding uptake inhibition.

PMID- 30301207
TI  - A Versatile Strategy for the Synthesis of 4,5-Dihydroxy-2,3-Pentanedione (DPD)
      and Related Compounds as Potential Modulators of Bacterial Quorum Sensing.
AB  - Resistance to antibiotics is an increasingly serious threat to global public
      health and its management translates to significant health care costs. The
      validation of new Gram-negative antibacterial targets as sources for potential
      new antibiotics remains a challenge for all the scientists working in this field.
      The interference with bacterial Quorum Sensing (QS) mechanisms represents a
      potentially interesting approach to control bacterial growth and pursue the next
      generation of antimicrobials. In this context, our research is focused on the
      discovery of novel compounds structurally related to (S)-4,5-dihydroxy-2,3
      pentanedione, commonly known as (S)-DPD, a small signaling molecule able to
      modulate bacterial QS in both Gram-negative and Gram-positive bacteria. In this
      study, a practical and versatile synthesis of racemic DPD is presented. Compared
      to previously reported syntheses, the proposed strategy is short and robust: it
      requires only one purification step and avoids the use of expensive or hazardous
      starting materials as well as the use of specific equipment. It is therefore well
      suited to the synthesis of derivatives for pharmaceutical research, as
      demonstrated by four series of novel DPD-related compounds described herein.

PMID- 30301208
TI  - Isolation of Nb2Se9 Molecular Chain from Bulk One-Dimensional Crystal by Liquid
      Exfoliation.
AB  - The optimum solvent for Nb2Se9 dispersion, which is a new type of one dimensional
      (1D) material, is investigated. Among several solvents (16 solvents in total),
      strong dispersion was observed in benzyl alcohol, isopropyl alcohol, isobutyl
      alcohol, and diacetone alcohol, which have medium dielectric constants in the
      range of 10 to 30 and surface tension in the range of 25 to 35 mJ m-2. 1D Nb2Se9
      chains, whose size is less than 10 nm, are well dispersed and it is possible to
      disperse mono-chains of 1 nm or less in a specific dispersion region. The 1D unit
      chain with dangling bond free surface and high volume to area ratio is expected
      to be used in applications that utilize the surface of the material. Such
      dispersion is an important first step towards various potential applications and
      is an indispensable scientific goal for the practical applications of Nb2Se9.

PMID- 30301209
TI  - Exploring the Emerging Evolution Trends of Urban Resilience Research by
      Scientometric Analysis.
AB  - : Numerous studies in urban resilience have been published in the past decade.
      However, only a few publications have tracked the evolution trends of urban
      resilience research, the findings of which can serve as a useful guide for
      scholars to foresee worth-effort research areas and make the best use of precious
      time and resources. In order to fill the research gap, this study performed a
      scientometric analysis on the evolution trends of urban resilience research using
      a versatile software package-CiteSpace. The scientomentric analysis focuses on
      distribution of lead authors and their institutions, high frequency categories
      and keywords, high influential journals, author contribution, and evolutionary
      trends based on co-author analysis, co-word analysis, co-citation analysis and
      cluster analysis of documents. This study discoveries that first, the U.S.,
      England, Australia, Canada, China and Sweden are the countries that make the most
      significant contributions in the advancement of urban resilience research;
      second, the existing urban resilience research focuses primarily on environmental
      studies, geography and planning development; third, hot topics of the urban
      resilience research keep shifting from 1993 to 2016; fourth, the knowledge body
      of urban resilience research consists of five clusters: resilience exploratory
      analysis, disaster resilience, urban resilience, urban resilience practice, and
      social-ecological systems; last, the emerging trends in urban resilience research
      include defining urban resilience, adaptation model, case studies, analytical
      methods and urban social-ecological systems, resulting in cutting-edge research
      areas in urban resilience.

PMID- 30301210
TI  - Arginine in the FARM and SARM: A Role in Chain-Length Determination for Arginine
      in the Aspartate-Rich Motifs of Isoprenyl Diphosphate Synthases from
      Mycobacterium tuberculosis.
AB  - Isoprenyl chains are found in many important metabolites. These are derived from
      precursors of the appropriate length produced by isoprenyl diphosphate synthases
      (IDSs). The human pathogen Mycobacterium tuberculosis makes various
      isoprenoids/terpenoids, with important roles in their biosynthesis played by two
      closely related IDSs, encoded by grcC1 (Rv0562) and grcC2 (Rv0989c), with Rv0989c
      generating the 10-carbon precursor (E)-geranyl diphosphate (GPP), and Rv0562 the
      20-carbon precursor (E,E,E)-geranylgeranyl diphosphate (GGPP). Intriguingly,
      while Rv0562 contains the prototypical trans-IDS first and second aspartate-rich
      (DDxxD) motifs (FARM and SARM, respectively), Rv0989c uniquely contains arginine
      in place of the second Asp in the FARM and first Asp in the SARM. Here site
      directed mutagenesis of the corresponding residues in both Rv0562 and Rv0989c
      reveals that these play a role in determination of product chain length.
      Specifically, substitution of Asp for the Arg in the FARM and SARM of Rv0989c
      leads to increased production of the longer 15-carbon farnesyl diphosphate (FPP),
      while substitution of Arg for the corresponding Asp in Rv0562 leads to increased
      release of shorter products, both FPP and GPP. Accordingly, while the primary
      role of the FARM and SARM is known to be chelation of the divalent magnesium ion
      co-factors that assist substrate binding and catalysis, the Arg substitutions
      found in Rv0989c seem to provide a novel means by which product chain length is
      moderated, at least in these M. tuberculosis IDSs.

PMID- 30301211
TI  - Consensus-Based Sequential Estimation of Process Parameters via Industrial
      Wireless Sensor Networks.
AB  - Process parameter estimation, to a large extent, determines the industrial
      production quality. However, limited sensors can be deployed in a traditional
      wired manner, which results in poor process parameter estimation in hostile
      environments. Industrial wireless sensor networks (IWSNs) are techniques that
      enrich sampling points by flexible sensor deployment and then purify the target
      by collaborative signal denoising. In this paper, the process industry scenario
      is concerned, where the workpiece is transferred on the belt and the parameter
      estimate is required before entering into the next process stage. To this end, a
      consensus-based sequential estimation (CSE) framework is proposed which utilizes
      the co-design of IWSN and parameter state estimation. First, a group-based
      network deployment strategy, together with a TDMA (Time division multiple access)
      based scheduling scheme is provided to track and sample the moving workpiece.
      Then, by matching to the tailored IWSN, the sequential estimation algorithm,
      which is based on the consensus-based Kalman estimation, is developed, and the
      optimal estimator that minimizes the mean-square error (MSE) is derived under the
      uncertain wireless communications. Finally, a case study on temperature
      estimation during the hot milling process is provided. The results show that the
      estimation error can be reduced to less than 3 ? C within a limited time period,
      although the measurement error can be more than 100 ? C in existing systems with
      a single-point temperature sensor.

PMID- 30301212
TI  - Protected Natural Areas: In Sickness and in Health.
AB  - Numerous studies show the benefits that contact with the natural environment have
      for human health, but there are few studies on the role of Protected Natural
      Areas (PNAs), either from the preventive point of view or on their potential
      benefits, on individuals with health problems. A study was made of the
      relationship between the visitation of Montseny Natural Park and Biosphere
      Reserve and health, from the perspective of a population group with different
      diseases. A total of 250 patients resident in the areas near the park were
      surveyed, recording their beliefs about the benefits of nature, as well as the
      reasons for visiting and the activities associated with health that they carried
      out in the park. The pure air is the most valued benefit (27.2%), particularly
      for those with allergies. The majority (57%) visit the park for health reasons.
      High levels (82%) of exercise are recorded, especially by patients with heart
      diseases (85%), and 65% exercised in the park. More physical activity is
      mentioned among those that visit the park most often, particularly among those
      that carried it out for health reasons. Plants were collected for medicinal use
      by 39.6%. The study confirmed the significant role of the Montseny Natural Park
      and Biosphere Reserve as a health resource for individuals with diseases that
      live near it. It also corroborates the beneficial effects that the PNA provide in
      human health.

PMID- 30301215
TI  - Elastic Properties of Magnetorheological Elastomers in a Heterogeneous Uniaxial
      Magnetic Field.
AB  - Magnetorheological elastomers (MREs) are stimulus-responsive soft materials that
      consist of polymeric matrices and magnetic particles. In this study, large-strain
      response of MREs with 5 vol % of carbonyl iron (CI) particles is experimentally
      characterized for two different conditions: (1) shear deformation in a uniform
      magnetic field; and (2), compression in a heterogeneous uniaxial magnetic field.
      For condition (1), dynamic viscoelastic measurements were performed using a
      rheometer with a rotor disc and an electric magnet that generated a uniform
      magnetic field on disc-like material samples. For condition (2), on the other
      hand, three permanent magnets with different surface flux densities were used to
      generate a heterogeneous uniaxial magnetic field under cylindrical material
      samples. The experimental results were mathematically modeled, and the
      relationship between them was investigated. We also used finite-element method
      (FEM) software to estimate the uniaxial distributions of the magnetic field in
      the analyzed MREs for condition (2), and developed mathematical models to
      describe these phenomena. By using these practicable techniques, we established a
      simple macroscale model of the elastic properties of MREs under simple
      compression. We estimated the elastic properties of MREs in the small-strain
      regime (neo-Hookean model) and in the large-strain regime (Mooney-Rivlin model).
      The small-strain model explains the experimental results for strains under 5%. On
      the other hand, the large-strain model explains the experimental results for
      strains above 10%.

PMID- 30301214
TI  - Pathophysiological Alterations of Redox Signaling and Endocannabinoid System in
      Granulocytes and Plasma of Psoriatic Patients.
AB  - Inflammatory granulocytes are characterized by an oxidative burst, which may
      promote oxidative stress and lipid modification both in affected tissues and on a
      systemic level. On the other hand, redox signaling involving lipid peroxidation
      products acting as second messengers of free radicals play important yet not
      fully understood roles in the pathophysiology of inflammation and various stress
      associated disorders. Therefore, the aim of this study was to evaluate the onset
      of oxidative stress and alterations of enzyme-dependent lipid metabolism
      resulting from redox imbalance in granulocytes and plasma obtained from patients
      with psoriasis vulgaris or psoriatic arthritis in comparison to the healthy
      subjects. The results obtained revealed enhanced activity of pro-oxidant enzymes
      nicotinamide adenine dinucleotide phosphate (NADPH) and xanthine oxidases in
      granulocytes with a decrease of enzymatic and non-enzymatic antioxidants in the
      plasma of psoriatic patients. The nuclear factor erythroid 2-related factor 2
      (Nrf2) and its regulators were increased in both forms of psoriasis while heme
      oxygenase 1 levels were increased only in psoriasis vulgaris. The redox imbalance
      was associated with decreased levels of phospholipids and of free polyunsaturated
      fatty acids but with enhanced activity of enzymes involved in lipid metabolism
      (phospholipase A2, acetylhydrolase PAF, cyclooxygenases 1 and 2) and increased
      lipid peroxidation products 4-hydroxynonenal, isoprostanes, and neuroprostanes.
      Increased endocannabinoids and G protein-coupled receptor 55 were observed in
      both forms of the disease while expression of the cannabinoid type 1 receptor
      (CB1) was increased only in patients with psoriatic arthritis, which is opposite
      to the cannabinoid type 2 receptor. This receptor was increased only in psoriasis
      vulgaris. Changes in protein expression promoted the apoptosis of granulocytes by
      increased caspases mainly in psoriasis vulgaris. This study indicates that
      inhibition of the Nrf2 pathway in psoriatic arthritis promotes a redox imbalance.
      In addition, increased expression of CB1 receptors leads to increased oxidative
      stress, lipid modifications, and inflammation, which, in turn, may promote the
      progression of psoriasis into the advanced, arthritic form of the disease.

PMID- 30301213
TI  - Role of Hypoxic Stress in Regulating Tumor Immunogenicity, Resistance and
      Plasticity.
AB  - Hypoxia, or gradients of hypoxia, occurs in most growing solid tumors and may
      result in pleotropic effects contributing significantly to tumor aggressiveness
      and therapy resistance. Indeed, the generated hypoxic stress has a strong impact
      on tumor cell biology. For example, it may contribute to increasing tumor
      heterogeneity, help cells gain new functional properties and/or select certain
      cell subpopulations, facilitating the emergence of therapeutic resistant cancer
      clones, including cancer stem cells coincident with tumor relapse and
      progression. It controls tumor immunogenicity, immune plasticity, and promotes
      the differentiation and expansion of immune-suppressive stromal cells. In this
      context, manipulation of the hypoxic microenvironment may be considered for
      preventing or reverting the malignant transformation. Here, we review the current
      knowledge on how hypoxic stress in tumor microenvironments impacts on tumor
      heterogeneity, plasticity and resistance, with a special interest in the impact
      on immune resistance and tumor immunogenicity.

PMID- 30301216
TI  - Recent Trends in Potential Therapeutic Applications of the Dietary Flavonoid
      Didymin.
AB  - Didymin (isosakuranetin 7-O-rutinoside) is an orally bioactive dietary flavonoid
      glycoside first found in citrus fruits. Traditionally, this flavonoid has long
      been used in Asian countries as a dietary antioxidant. Recent studies have
      provided newer insights into this pleiotropic compound, which could regulate
      multiple biological activities of many important signaling molecules in health
      and disease. Emerging data also presented the potential therapeutic application
      of dietary flavonoid glycoside didymin against cancer, neurological diseases,
      liver diseases, cardiovascular diseases, and other diseases. In this review, we
      briefly introduce the source and extraction methods of didymin, and summarize its
      potential therapeutic application in the treatment of various diseases, with an
      emphasis on molecular targets and mechanism that contributes to the observed
      therapeutic effects. The dietary flavonoid didymin can be used to affect health
      and disease with multiple therapeutic targets, and it is anticipated that this
      review will stimulate the future development of this potential dietary medicine.

PMID- 30301217
TI  - Synthesis, Molecular Docking and in Vitro Screening of Some Newly Synthesized
      Triazolopyridine, Pyridotriazine and Pyridine-Pyrazole Hybrid Derivatives.
AB  - A series of novel pyridine and fused pyridine derivatives have been prepared
      starting from 6-(3,4-dimethylphenyl)-2-hydrazinyl-4-(thiophen-2-yl)-pyridine-3
      carbonitrile 1 which on treatment with appropriate formic acid, acetic acid/
      acetic anhydride, benzoyl chloride and/or carbon disulfide afforded the
      corresponding triazolopyridine derivatives 2-5. Also, treatment of hydrazide 1
      with diethyloxalate, chloroacetyl chloride, chloroacetic acid and/or 1,2
      dichloroethane yielded the corresponding pyridotriazine derivatives 7-10. Further
      transformation of compound 1 with a different active methylene group, namely
      acetyl acetone, diethylmalonate, ethyl cyanoacetate, ethyl benzoylacetate and/or
      ethyl acetoacetate, produced the pyridine-pyrazole hybrid derivatives 11-15.
      These newly synthesized compounds (1-15) were subjected to in silico molecular
      docking screenings towards GlcN-6-P synthase as the target protein. The results
      revealed moderate to good binding energies of the ligands on the target protein.
      All the newly prepared products exhibited antimicrobial and antioxidant activity.

PMID- 30301218
TI  - FBXL7 Upregulation Predicts a Poor Prognosis and Associates with a Possible
      Mechanism for Paclitaxel Resistance in Ovarian Cancer.
AB  - Paclitaxel (PTX) is a common regimen used to treat patients with ovarian cancer.
      Although approximately 60% of ovarian cancer patients exhibit a pathologic
      complete response (pCR), approximately 40% of patients appear to be insensitive
      to PTX adjuvant therapy. Thus, identifying a useful biomarker to predict pCR
      would be of great help to ovarian cancer patients who decide to receive PTX
      treatment. We found that FBXL7 was downregulated in OVSAHO (PTX-sensitive) but
      upregulated in KURAMOCHI (PTX-resistant) cells after PTX treatment at cytotoxic
      concentrations. Moreover, our data showed that the fold change of FBXL7
      expression post-treatment with PTX was causally correlated with the 50%
      inhibitory concentrations (IC50) of PTX in a panel of ovarian cancer cell lines.
      In assessments of progression-free survival probability, high levels of FBXL7
      transcript strongly predicted a poor prognosis and unfavorable response to PTX
      based chemotherapy in patients with ovarian cancer. The knockdown of FBXL7
      predominantly enhanced the cytotoxic effectiveness of PTX on the PTX-resistant
      KURAMOCHI cells. FBXL7 may be a useful biomarker for predicting complete
      pathologic response in ovarian cancer patients who decide to receive post
      operative PTX therapy.

PMID- 30301219
TI  - Effects of Different Techniques of Malolactic Fermentation Induction on Diacetyl
      Metabolism and Biosynthesis of Selected Aromatic Esters in Cool-Climate Grape
      Wines.
AB  - The effects of different malolactic bacteria fermentation techniques on the
      bioconversion of aromatic compounds in cool-climate grape wines were examined.
      During three wine seasons, red and white grape wines were produced using various
      malolactic fermentation induction techniques: Coinoculation, sequential
      inoculation, and spontaneous process. Volatile compounds (diacetyl and the
      products of its metabolism, and selected ethyl fatty acid esters) were extracted
      by solid phase microextraction. Compounds were identified with a multidimensional
      gas chromatograph-GC * GC-ToFMS with ZOEX cryogenic (N2) modulator. Sensory
      evaluation of the wines was also performed. It was found that the fermentation
      derived metabolites studied were affected by the malolactic bacteria inoculation
      regime. Quantitatively, ethyl lactate, diethyl succinate, and ethyl acetate
      dominated as esters with the largest increase in content. The total concentration
      of ethyl esters was highest for the coinoculation technique, while the highest
      concentration of diacetyl was noted for the spontaneous technique. Controlled
      malolactic fermentation, especially using the coinoculation technique, can be
      proposed as a safe and efficient enological practice for producing quality cool
      climate grape wines enriched with fruity, fresh, and floral aromas.

PMID- 30301221
TI  - Object Detection in Very High-Resolution Aerial Images Using One-Stage Densely
      Connected Feature Pyramid Network.
AB  - Object detection in very high-resolution (VHR) aerial images is an essential step
      for a wide range of applications such as military applications, urban planning,
      and environmental management. Still, it is a challenging task due to the
      different scales and appearances of the objects. On the other hand, object
      detection task in VHR aerial images has improved remarkably in recent years due
      to the achieved advances in convolution neural networks (CNN). Most of the
      proposed methods depend on a two-stage approach, namely: a region proposal stage
      and a classification stage such as Faster R-CNN. Even though two-stage approaches
      outperform the traditional methods, their optimization is not easy and they are
      not suitable for real-time applications. In this paper, a uniform one-stage model
      for object detection in VHR aerial images has been proposed. In order to tackle
      the challenge of different scales, a densely connected feature pyramid network
      has been proposed by which high-level multi-scale semantic feature maps with high
      quality information are prepared for object detection. This work has been
      evaluated on two publicly available datasets and outperformed the current state
      of-the-art results on both in terms of mean average precision (mAP) and
      computation time.

PMID- 30301220
TI  - Maize WRKY Transcription Factor ZmWRKY106 Confers Drought and Heat Tolerance in
      Transgenic Plants.
AB  - WRKY transcription factors constitute one of the largest transcription factor
      families in plants, and play crucial roles in plant growth and development,
      defense regulation and stress responses. However, knowledge about this family in
      maize is limited. In the present study, we identified a drought-induced WRKY
      gene, ZmWRKY106, based on the maize drought de novo transcriptome sequencing
      data. ZmWRKY106 was identified as part of the WRKYII group, and a phylogenetic
      tree analysis showed that ZmWRKY106 was closer to OsWRKY13. The subcellular
      localization of ZmWRKY106 was only observed in the nucleus. The promoter region
      of ZmWRKY106 included the C-repeat/dehydration responsive element (DRE), low
      temperature responsive element (LTR), MBS, and TCA-elements, which possibly
      participate in drought, cold, and salicylic acid (SA) stress responses. The
      expression of ZmWRKY106 was induced significantly by drought, high temperature,
      and exogenous abscisic acid (ABA), but was weakly induced by salt. Overexpression
      of ZmWRKY106 improved the tolerance to drought and heat in transgenic Arabidopsis
      by regulating stress-related genes through the ABA-signaling pathway, and the
      reactive oxygen species (ROS) content in transgenic lines was reduced by
      enhancing the activities of superoxide dismutase (SOD), peroxide dismutase (POD),
      and catalase (CAT) under drought stress. This suggested that ZmWRKY106 was
      involved in multiple abiotic stress response pathways and acted as a positive
      factor under drought and heat stress.

PMID- 30301223
TI  - Testing New Concepts for Crop Cultivation in Space: Effects of Rooting Volume and
      Nitrogen Availability.
AB  - Long term human missions to the Moon and Mars, rely on life support systems for
      food production and regeneration of resources. In the EU H2020 TIME SCALE
      project, an advanced life support system concept was developed to facilitate
      plant research and technology demonstration under different gravity conditions.
      Ground experiments assessed irrigation systems and effects of rooting- and
      nutrient solution volume. The maximal allowed volume for existing International
      Space Station research facilities (3.4 L) was able to support cultivation of two
      lettuce heads for at least 24 days. A smaller rooting volume (0.6 L) increased
      root biomass after 24 days, but induced a 5% reduction in total biomass at day
      35. Regulating effects of nitrate supply on plant water fluxes in light and dark
      were also investigated. At low concentrations of nitrate in the nutrient
      solution, both transpiration and stomatal conductance increased rapidly with
      increasing nitrate concentration. During day-time this increase levelled off at
      high concentrations, while during nigh-time there was a distinct decline at supra
      optimal concentrations. Plants supplied with nitrate concentrations as low as
      1.25 mM did not show visible signs of nutrient stress or growth reduction. These
      findings hold promise for both reducing the environmental impact of terrestrial
      horticulture and avoiding nutrient stress in small scale closed cultivation
      systems for space.

PMID- 30301222
TI  - MDA-MB-231 Breast Cancer Cells and Their CSC Population Migrate Towards Low
      Oxygen in a Microfluidic Gradient Device.
AB  - Most cancer deaths are caused by secondary tumors formed through metastasis, yet
      due to our limited understanding of this process, prevention remains a major
      challenge. Recently, cancer stem cells (CSCs) have been proposed as the source of
      metastases, but only little is known about their migratory behavior. Oxygen
      gradients in the tumor have been linked to directional migration of breast cancer
      cells. Here, we present a method to study the effect of oxygen gradients on the
      migratory behavior of breast CSCs using a microfluidic device. Our chip contains
      a chamber in which an oxygen gradient can be generated between hypoxic (<1%) and
      ambient (21%) conditions. We tracked the migration of CSCs obtained from MDA-MB
      231 breast cancer cells, and found that their migration patterns do not differ
      from the average MDA-MB-231 population. Surprisingly, we found that the cells
      migrate towards low oxygen levels, in contrast with an earlier study. We
      hypothesize that in our device, migration is exclusively due to the pure oxygen
      gradient, whereas the effects of oxygen in earlier work were obscured by
      additional cues from the tumor microenvironment (e.g., nutrients and
      metabolites). These results open new research directions into the role of oxygen
      in directing cancer and CSC migration.

PMID- 30301224
TI  - In Vitro and in Vivo Imaging of Nitroxyl with Copper Fluorescent Probe in Living
      Cells and Zebrafish.
AB  - Nitroxyl (HNO) plays a critical role in many physiological processes which
      includes vasorelaxation in heart failure, neuroregulation, and myocardial
      contractility. Powerful imaging tools are required to obtain information for
      understanding the mechanisms involved in these in vivo processes. In order to
      develop a rapid and high sensitive probe for HNO detection in living cells and
      the zebrafish model organism, 2-((2-(benzothiazole-2yl)benzylidene) amino)benzoic
      acid (AbTCA) as a ligand, and its corresponding copper(II) complex Cu(II)-AbTCA
      were synthesized. The reaction results of Cu(II)-AbTCA with Angeli's salt showed
      that Cu(II)-AbTCA could detect HNO quantitatively in a range of 40-360 uM with a
      detection limit of 9.05 uM. Furthermore, Cu(II)-AbTCA is more selective towards
      HNO over other biological species including thiols, reactive nitrogen, and
      reactive oxygen species. Importantly, Cu(II)-AbTCA was successfully applied to
      detect HNO in living cells and zebrafish. The collective data reveals that Cu(II)
      AbTCA could be used as a potential probe for HNO detection in living systems.

PMID- 30301225
TI  - A Novel Non-Enzymatic Electrochemical Hydrogen Peroxide Sensor Based on a Metal
      Organic Framework/Carbon Nanofiber Composite.
AB  - A co-based porous metal-organic framework (MOF) of zeolitic imidazolate framework
      67 (ZIF-67) and carbon nanofibers (CNFs) was utilized to prepare a ZIF-67/CNFs
      composite via a one-pot synthesis method. Scanning electron microscopy (SEM),
      energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD) were
      employed to investigate the morphology, structure, and composition of the
      resulting composite. A novel high-performance non-enzymatic electrochemical
      sensor was constructed based on the ZIF-67/CNFs composite. The ZIF-67/CNFs based
      sensor exhibited enhanced electrocatalytic activity towards H2O2 compared to a
      pure ZIF-67-based sensor, due to the synergistic effects of ZIF-67 and CNFs.
      Meanwhile, chronoamperometry was utilized to explore the detection performance of
      the sensor. Results showed the sensor displayed high-efficiency electrocatalysis
      towards H2O2 with a detection limit of 0.62 MUM (S/N = 3), a sensitivity of 323
      uA mM-1 cm-2, a linear range from 0.0025 to 0.19 mM, as well as satisfactory
      selectivity and long-term stability. Furthermore, the sensor demonstrated its
      application potential in the detection of H2O2 in food.

PMID- 30301226
TI  - Composition Analysis by UPLC-PDA-ESI (-)-HRMS and Antioxidant Activity Using
      Saccharomyces cerevisiae Model of Herbal Teas and Green Teas from Hainan.
AB  - Different teas from everywhere are very useful and have been extensively studied.
      We studied the antioxidant activity of herbal teas and green teas from Hainan,
      Mallotus oblongifolius Muell. Arg. (MO), Ilex kudingcha C.J. Tseng (KD), Camellia
      sinensis var. assamica (J. W. Mast.) Kitam. Hainan Dayezhong (DY), and Camellia
      sinensis (L.) O. Ktze. (produced from Hainan Baisha (BS)). The total phenol
      content and total flavonoid content from water extracts, resin extracts and
      fractions of herbal teas and green teas were compared. Later, eight fractions of
      herbal teas and green teas were subjected to UPLC-PDA-ESI-(-)-HRMS. We determined
      1-diphenyl -2-picryl-hydrazyl radical and hydroxyl free radical scavenging
      activity by electron paramagnetic resonance spectroscopy. We subjected
      Saccharomyces cerevisiae to hydrogen peroxide, stress and evaluated antioxidant
      activity of herbal teas and green teas in cellulo. The experiment identified more
      than 14 potential antioxidant compounds from herbal teas and green teas. The
      herbal teas and green teas had a clearance rate higher than ferulic acid at the
      same concentrations. MO best reduced intracellular oxidation levels and increased
      catalase, glutathione reductase activities, glutathione reduced and glutathione
      oxidized content. KD had the highest cell survival rate and reduced cell lipid
      peroxidation. DY best improved superoxide dismutase activity and BS was the most
      active in the halo test. Therefore, we concluded that MO had stronger antioxidant
      activity than other herbal teas and green teas from Hainan, especially, which
      reduce S. cerevisiae oxidative stress under H2O2 stress.

PMID- 30301228
TI  - Green Procurement Relationships Development under Carbon Emissions Regulations: A
      Bi-Level Programming Approach.
AB  - A multi-period Stackelberg game is adopted to study a green procurement
      relationship between manufacturers and suppliers in a supply chain. The
      manufacturers are considered as leaders, while the suppliers are modelled as
      followers in this Stackelberg game. Accordingly, a mixed binary linear bi-level
      programming model is developed to elaborate the game in consideration of carbon
      tax scheme. The upper level (the leader) aims at selecting a proper number of
      suitable suppliers to provide heterogeneous raw materials at the lowest
      operational cost. The objective of the lower level (the follower) is to find
      optimal purchasing quantities of raw materials. In addition, two lemmas are
      introduced to transform the mixed linear bi-level programming model into a single
      level linear programming model. The numerical example illustrates that: (1) the
      manufacturer prefers to adopt the multiple sourcing strategy due to the
      flexibility; (2) keeping stable supplies and large order volumes could
      effectively reduce carbon emissions for the suppliers and make the supply chain
      greener.

PMID- 30301227
TI  - Evaluation of Circulating MicroRNA Biomarkers in the Acute Pancreatic Injury Dog
      Model.
AB  - This study aimed to evaluate the usefulness of four microRNAs (miRNAs) in an
      acute pancreatic injury dog model. Acute pancreatitis was induced by infusion of
      cerulein for 2 h (7.5 MUg/kg/h). The levels of well-known miRNAs, microRNA-216a
      (miR-216a) and microRNA-375 (miR-375), and new candidates microRNA-551b (miR
      551b), and microRNA-7 (miR-7), were measured at 0, 0.5, 1, 2, 6, 12, and 24 h
      with serum amylase and lipase, and histopathological examination was performed.
      Among the four miRNAs, miR-216a and miR-375, and serum enzymes were significantly
      increased by cerulein treatment. The expression levels of miRNAs and serum
      enzymes peaked at 2-6 h with a similar pattern; however, the overall increases in
      miR-216a and miR-375 levels were much higher than those of the serum enzyme
      biomarkers. Increased levels of miR-216a and miR-375 were most highly correlated
      to the degree of individual histopathological injuries of the pancreas, and
      showed much greater dynamic response than serum enzyme biomarkers. Twenty-four
      hour time-course analysis in this study revealed time-dependent changes of miRNA
      expression levels, from initial increase to decrease by predose level in acute
      pancreatitis. Our findings demonstrate that, in dogs, miR-216a and miR-375 have
      the potential to sensitively detect pancreatitis and reflect well the degree of
      pancreatic injury, whereas miR-551b and miR-7 do not.

PMID- 30301230
TI  - Microdialysis-Assessed Adipose Tissue Metabolism, Circulating Cytokines and
      Outcome in Critical Illness.
AB  - Microdialysis (MD) can provide continuous information about tissue composition.
      To assess in critically ill patients adipose tissue metabolic patterns, the
      relationships between metabolic patterns and blood cytokine concentration
      associations of adipose tissue energy metabolism and clinical outcome we studied
      203 mechanically ventilated general intensive care unit (ICU) patients. Upon ICU
      admission an MD catheter was inserted into the subcutaneous adipose tissue of the
      upper thigh to measure lactate (L), glucose, pyruvate (P), and glycerol. Serum
      concentrations of IL-10, IL-6, IL-8, and TNF-alpha were determined within 48 h
      from ICU admission. Mitochondrial dysfunction was defined as L/P ratio >30 and
      pyruvate >=70 MUmol/L, ischemia as L/P ratio >30 and pyruvate <70 MUmol/L and no
      ischemia/no mitochondrial dysfunction (i.e. aerobic metabolism) was as L/P ratio
      <=30. Metabolism was aerobic in 74% of patients. In 13% of patients there was
      biochemical evidence of ischemia and in 13% of patients of mitochondrial
      dysfunction. Mitochondrial dysfunction was associated with poor outcome. In
      conclusion, MD showed that about two thirds of critically ill patients have
      normal aerobic adipose tissue metabolism. Mitochondrial dysfunction was not
      common but was associated with poor outcome. Identifying subgroups of critically
      ill patients is crucial as different treatment strategies may improve survival.

PMID- 30301229
TI  - Whole Genome Characterization of Orthopoxvirus (OPV) Abatino, a Zoonotic Virus
      Representing a Putative Novel Clade of Old World Orthopoxviruses.
AB  - Orthopoxviruses (OPVs) are diffused over the complete Eurasian continent, but
      previously described strains are mostly from northern Europe, and few infections
      have been reported from Italy. Here we present the extended genomic
      characterization of OPV Abatino, a novel OPV isolated in Italy from an infected
      Tonkean macaque, with zoonotic potential. Phylogenetic analysis based on 102
      conserved OPV genes (core gene set) showed that OPV Abatino is most closely
      related to the Ectromelia virus species (ECTV), although placed on a separate
      branch of the phylogenetic tree, bringing substantial support to the hypothesis
      that this strain may be part of a novel OPV clade. Extending the analysis to the
      entire set of genes (coding sequences, CDS) further substantiated this
      hypothesis. In fact the genome of OPV Abatino included more CDS than ECTV; most
      of the extra genes (mainly located in the terminal genome regions), showed the
      highest similarity with cowpox virus (CPXV); however vaccinia virus (VACV) and
      monkeypox virus (MPXV) were the closest OPV for certain CDS. These findings
      suggest that OPV Abatino could be the result of complex evolutionary events,
      diverging from any other previously described OPV, and may indicate that
      previously reported cases in Italy could represent the tip of the iceberg yet to
      be explored.

PMID- 30301231
TI  - TRP Channels as Drug Targets to Relieve Itch.
AB  - Although acute itch has a protective role by removing irritants to avoid further
      damage, chronic itch is debilitating, significantly impacting quality of life.
      Over the past two decades, a considerable amount of stimulating research has been
      carried out to delineate mechanisms of itch at the molecular, cellular, and
      circuit levels. There is growing evidence that transient receptor potential (TRP)
      channels play important roles in itch signaling. The purpose of this review is to
      summarize our current knowledge about the role of TRP channels in the generation
      of itch under both physiological and pathological conditions, thereby identifying
      them as potential drug targets for effective anti-itch therapies.

PMID- 30301232
TI  - Effect of Straw Checkerboards on Wind Proofing, Sand Fixation, and Ecological
      Restoration in Shifting Sandy Land.
AB  - Due to their simple layout and adaptability to various environments, straw
      checkerboards are widely used to control windblown sand in China. To fully
      understand the wind proofing and sand-fixing benefits of different board
      specifications, and to determine the restorative effects of straw checkerboard,
      we tested different sizes of checkerboard, determined their performance as a
      windbreak and in trapping shifting sand, and constructed models based on wind
      tunnel tests, enabling the wind speed flow field to be analysed. We also sampled
      the soil in areas where straw checkerboards had been established for several
      years and analysed the trends in soil physical and chemical properties over time.
      We found that all sizes of straw checkerboard effectively reduced the wind speed
      near the surface and formed a protected area, with the best protective effect
      achieved for a one-meter board. All sizes of straw checkerboard effectively
      intercepted windblown sand to form surface accumulation, with the one-meter board
      again showing the best performance. The use of a straw checkerboard also
      effectively improved the physical and chemical properties of soil and promoted
      ecological restoration. These results indicate that straw checkerboards are a low
      cost engineering measure that could play an important role in desertification
      control and the ecological restoration of sandy land ecosystems.

PMID- 30301233
TI  - Mitigated Impact of Provision of Local Foods Combined with Nutrition Education
      and Counseling on Young Child Nutritional Status in Cambodia.
AB  - BACKGROUND: In Cambodia, stunting and wasting affect, respectively, 32% and 10%
      of children 0-59 months while 55% are anemic. Our research aims to assess the
      efficiency of two local foods combined with nutritional education and counseling
      (CEN) activities as compared to CEN alone on improving child nutritional status
      and dietary intake. METHODS: A cluster-randomized controlled trial was conducted
      in Soth Nikum area over a six-month period among children 6-23 months (n = 360)
      assigned to receive either moringa +CEN, cricket +CEN or CEN alone.
      Anthropometric measurements were performed and hemoglobin and ferritin levels
      assessed. RESULTS: Overall, no significant increase in the mean length/height-for
      age z-score was observed, although a small increase of the weight-for
      length/height was noted in intervention groups. Hemoglobin and ferritin mean
      values increased in all groups. The degree of satisfaction of energy, proteins,
      iron, and zinc requirements improved in all groups, but to a greater extent in
      the intervention groups and more children were healthy. CONCLUSION: Our research
      shows no significant impact of the provision of two local foods combined with CEN
      on the improvement of child nutritional status as compared to CEN alone. However,
      children consuming them better fulfilled their energy, iron, and zinc
      requirements and were healthier.

PMID- 30301234
TI  - Design of Antibacterial Agents: Alkyl Dihydroxybenzoates against Xanthomonas
      citri subsp. citri.
AB  - Xanthomonas citri subsp. citri (Xcc) causes citrus canker, affecting sweet orange
      producing areas around the world. The current chemical treatment available for
      this disease is based on cupric compounds. For this reason, the objective of this
      study was to design antibacterial agents. In order to do this, we analyzed the
      anti-Xcc activity of 36 alkyl dihydroxybenzoates and we found 14 active
      compounds. Among them, three esters with the lowest minimum inhibitory
      concentration values were selected; compounds 4 (52 MUM), 16 (80 MUM) and 28 (88
      MUM). Our study demonstrated that alkyl dihydroxybenzoates cause a delay in the
      exponential phase. The permeability capacity of alkyl dihydroxybenzoates in a
      quarter of MIC was compared to nisin (positive control). Compound 28 was the most
      effective (93.8), compared to compound 16 (41.3) and compound 4 (13.9) by
      percentage values. Finally, all three compounds showed inhibition of FtsZ GTPase
      activity, and promoted changes in protofilaments, leading to depolymerization,
      which prevents bacterial cell division. In conclusion, heptyl dihydroxybenzoates
      (compounds 4, 16 and 28) are promising anti-Xcc agents which may serve as an
      alternative for the control of citrus canker.

PMID- 30301236
TI  - Determinants of Breeding Farmers' Safe Use of Veterinary Drugs: A Theoretical and
      Empirical Analysis.
AB  - As food safety has attracted the widespread attention of society, the quality
      safety of agricultural products has become an important part of food safety and
      also confronts multiple challenges. In fact, the safe use of veterinary drugs in
      the production process has become one of important guarantees for the quality
      safety of agricultural products. It's of great significance to regulate the
      breeding farmers' safe use of veterinary drugs and to create a safe and healthy
      production environment for agricultural products. A field survey of individual
      and large-scale swine breeding farmers in four typical provinces including Henan,
      Shandong, Jiangxi and Guizhou generated 397 questionnaires. This field survey
      conducted the internal and external classification of breeding farmers' safe use
      of veterinary drugs and defined the breeding farmers' safe use of veterinary
      drugs in the light of dosage, type and standardized operation of veterinary
      drugs. Based on Lewin's behavior theory, the survey used the structural equation
      modeling method to systematically examine the generation path of breeding
      farmers' safe use of veterinary drugs. The comprehensive analysis reveals that
      breeding farmers' knowledge about veterinary drugs, the attitudes toward the
      government supervision and the market environment of breeding activities all
      exert some effects on breeding farmers' use of veterinary drugs. Some suggestions
      and countermeasures for breeding farmers' safe use of veterinary drugs are
      provided as follows: First, more efforts should be pumped into publicity and
      instruction so that breeding farmers can have a better understanding of
      veterinary drugs. Second, preferential policies should be formulated to encourage
      the breeding farmers' participation in the industrial organizations of swine
      breeding farmers, and advocate the industrial organizations' active provision of
      different technical trainings. Third, the communication and cooperation platform
      should be created among breeding farmers, slaughter and processing plants and
      supermarkets, the poultry insurance market should be regulated, and the insurance
      purchase process should be improved. Fourth, when more subsidies for harm-free
      and environment-friendly veterinary drugs are provided, more serious punishments
      should be imposed on the unsafe use of veterinary drugs to offer policy support
      for the breeding farmers' standardized use of veterinary drugs.

PMID- 30301235
TI  - Movement of the RecG Motor Domain upon DNA Binding Is Required for Efficient Fork
      Reversal.
AB  - RecG catalyzes reversal of stalled replication forks in response to replication
      stress in bacteria. The protein contains a fork recognition ("wedge") domain that
      binds branched DNA and a superfamily II (SF2) ATPase motor that drives
      translocation on double-stranded (ds)DNA. The mechanism by which the wedge and
      motor domains collaborate to catalyze fork reversal in RecG and analogous
      eukaryotic fork remodelers is unknown. Here, we used electron paramagnetic
      resonance (EPR) spectroscopy to probe conformational changes between the wedge
      and ATPase domains in response to fork DNA binding by Thermotoga maritima RecG.
      Upon binding DNA, the ATPase-C lobe moves away from both the wedge and ATPase-N
      domains. This conformational change is consistent with a model of RecG fully
      engaged with a DNA fork substrate constructed from a crystal structure of RecG
      bound to a DNA junction together with recent cryo-electron microscopy (EM)
      structures of chromatin remodelers in complex with dsDNA. We show by mutational
      analysis that a conserved loop within the translocation in RecG (TRG) motif that
      was unstructured in the RecG crystal structure is essential for fork reversal and
      DNA-dependent conformational changes. Together, this work helps provide a more
      coherent model of fork binding and remodeling by RecG and related eukaryotic
      enzymes.

PMID- 30301237
TI  - Associations between Body Mass Index and Urban "Green" Streetscape in Cleveland,
      Ohio, USA.
AB  - Public health researchers are increasingly interested in assessing the impact of
      neighborhood environment on physical activities and chronic health issues among
      humans. Walkable streets and proximity to green space have long been believed to
      promote active lifestyles in cities, which contribute to positive health outcomes
      among residents. Traditionally, urban environmental metrics were calculated at
      the area level to describe the physical environment of neighborhoods. However,
      considering the fact that streets are the basic unit for human activities in
      cities, it is important to understand how the streetscape environment can
      influence human health conditions. In this study, we investigated the influence
      of street greenery and walkability on body mass index in Cleveland, Ohio, USA.
      Different from the area level and overhead view greenery metrics, we used the
      green view index calculated from the Google Street View to represent the amount
      of street greenery. The Walk Score was used to indicate the walkability of
      neighborhoods also at the street level. Statistical analysis results show that
      the Walk Score has a more significant association with decreased BMI for males
      than females and the street greenery has a more significant association with
      decreased BMI for females than males in Cleveland, Ohio. The results of this
      study would provide a reference for designing gender-specific healthy cities.

PMID- 30301239
TI  - BATS: Adaptive Ultra Low Power Sensor Network for Animal Tracking.
AB  - In this paper, the BATS project is presented, which aims to track the behavior of
      bats via an ultra-low power wireless sensor network. An overview about the whole
      project and its parts like sensor node design, tracking grid and software
      infrastructure is given and the evaluation of the project is shown. The BATS
      project includes a lightweight sensor node that is attached to bats and combines
      multiple features. Communication among sensor nodes allows tracking of bat
      encounters. Flight trajectories of individual tagged bats can be recorded at high
      spatial and temporal resolution by a ground node grid. To increase the
      communication range, the BATS project implemented a long-range telemetry system
      to still receive sensor data outside the standard ground node network. The whole
      system is designed with the common goal of ultra-low energy consumption while
      still maintaining optimal measurement results. To this end, the system is
      designed in a flexible way and is able to adapt its functionality according to
      the current situation. In this way, it uses the energy available on the sensor
      node as efficient as possible.

PMID- 30301240
TI  - Should I Eat or Should I Go? Acridid Grasshoppers and Their Novel Host Plants:
      Potential for Biotic Resistance.
AB  - Novel, non-coevolved associations between introduced plants and native insect
      herbivores may lead to changes in trophic interactions in native communities, as
      well as to substantial economic problems. Although some studies in invasion
      ecology demonstrated that native herbivores can preferentially feed on introduced
      plants and therefore contribute to the biotic resistance of native communities to
      plant invasions, the role of acridid grasshoppers as native generalist insect
      herbivores is largely overlooked. This systematic review aimed to identify
      patterns of grasshopper feeding preferences for native versus introduced plants
      and, consequently, a potential of grasshoppers to provide biotic resistance of
      native communities. The analysis of 63 records of feeding preference trials for
      28 North-American grasshopper species (retrieved from 2146 studies published
      during 1967-2017) has demonstrated a preference of grasshoppers for introduced
      host plants, and identified 12 preferred introduced plants with high or middle
      invasive ranks. A significant effect of the life stage (p < 0.001), but not the
      experimental environment, plant material, and measurements, on grasshopper
      preferences for introduced plants was also detected. Overall, results suggest a
      potential of acridid grasshoppers to contribute to the biotic resistance of
      native communities. The review also provides methodological recommendations for
      future experimental studies on grasshopper-host plant interactions.

PMID- 30301238
TI  - EEG-Based Control for Upper and Lower Limb Exoskeletons and Prostheses: A
      Systematic Review.
AB  - Electroencephalography (EEG) signals have great impact on the development of
      assistive rehabilitation devices. These signals are used as a popular tool to
      investigate the functions and the behavior of the human motion in recent
      research. The study of EEG-based control of assistive devices is still in early
      stages. Although the EEG-based control of assistive devices has attracted a
      considerable level of attention over the last few years, few studies have been
      carried out to systematically review these studies, as a means of offering
      researchers and experts a comprehensive summary of the present, state-of-the-art
      EEG-based control techniques used for assistive technology. Therefore, this
      research has three main goals. The first aim is to systematically gather,
      summarize, evaluate and synthesize information regarding the accuracy and the
      value of previous research published in the literature between 2011 and 2018. The
      second goal is to extensively report on the holistic, experimental outcomes of
      this domain in relation to current research. It is systematically performed to
      provide a wealthy image and grounded evidence of the current state of research
      covering EEG-based control for assistive rehabilitation devices to all the
      experts and scientists. The third goal is to recognize the gap of knowledge that
      demands further investigation and to recommend directions for future research in
      this area.

PMID- 30301241
TI  - Acute Effects of Substitution, and Addition, of Carbohydrates and Fat to Protein
      on Gastric Emptying, Blood Glucose, Gut Hormones, Appetite, and Energy Intake.
AB  - Whey protein, when ingested on its own, load-dependently slows gastric emptying
      and stimulates gut hormone concentrations in healthy young men. The aim of this
      study was to determine the effects of substitution, and addition, of carbohydrate
      (dextrose) and fat (olive oil) to whey protein. In randomized, double-blind
      order, 13 healthy young men (age: 23 +/- 1 years, body mass index: 24 +/- 1
      kg/m2) ingested a control drink (450 mL; ~2 kcal/'control') or iso-volumetric
      drinks containing protein/carbohydrate/fat: (i) 14 g/28 g/12.4 g (280
      kcal/'M280'), (ii) 70 g/28 g/12.4 g (504kcal/'M504'), and (iii) 70 g/0 g/0 g (280
      kcal/'P280'), on 4 separate study days. Gastric emptying (n = 11, 3D
      ultrasonography), blood glucose, plasma insulin, ghrelin, cholecystokinin (CCK)
      and glucagon-like peptide-1 (GLP-1) concentrations (0-180 min), appetite (visual
      analogue scales), and ad-libitum buffet-meal energy intake (180-210 min) were
      determined. Substitution of protein with carbohydrate and fat was associated with
      faster gastric emptying (lower 50% emptying time (T50)), reduced suppression of
      ghrelin, and stimulation of GLP-1 (all P < 0.001); while the addition of
      carbohydrate and fat to protein did not affect gastric emptying or gut hormone
      responses significantly. Total energy intake (i.e., drink plus meal) was greater
      after all caloric drinks than control (P < 0.001). In conclusion, substitution of
      whey protein with dextrose and olive oil accelerated gastric emptying. Higher
      protein content of a mixed macronutrient drink increased gut hormone and insulin
      responses.

PMID- 30301242
TI  - Lung Diseases: Chronic Respiratory Infections.

PMID- 30301243
TI  - Decision-Tree Based Meta-Strategy Improved Accuracy of Disorder Prediction and
      Identified Novel Disordered Residues Inside Binding Motifs.
AB  - Using computational techniques to identify intrinsically disordered residues is
      practical and effective in biological studies. Therefore, designing novel high
      accuracy strategies is always preferable when existing strategies have a lot of
      room for improvement. Among many possibilities, a meta-strategy that integrates
      the results of multiple individual predictors has been broadly used to improve
      the overall performance of predictors. Nonetheless, a simple and direct
      integration of individual predictors may not effectively improve the performance.
      In this project, dual-threshold two-step significance voting and neural networks
      were used to integrate the predictive results of four individual predictors,
      including: DisEMBL, IUPred, VSL2, and ESpritz. The new meta-strategy has improved
      the prediction performance of intrinsically disordered residues significantly,
      compared to all four individual predictors and another four recently-designed
      predictors. The improvement was validated using five-fold cross-validation and in
      independent test datasets.

PMID- 30301244
TI  - An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein
      Affects Viral RNA Synthesis and Attenuates the Virus In Vivo.
AB  - The recent outbreaks of Zika virus (ZIKV), its association with Guillain-Barre
      syndrome and fetal abnormalities, and the lack of approved vaccines and
      antivirals, highlight the importance of developing countermeasures to combat ZIKV
      disease. In this respect, infectious clones constitute excellent tools to
      accomplish these goals. However, flavivirus infectious clones are often difficult
      to work with due to the toxicity of some flavivirus sequences in bacteria. To
      bypass this problem, several alternative approaches have been applied for the
      generation of ZIKV clones including, among others, in vitro ligation, insertions
      of introns and using infectious subgenomic amplicons. Here, we report a simple
      and novel DNA-launched approach based on the use of a bacterial artificial
      chromosome (BAC) to generate a cDNA clone of Rio Grande do Norte Natal ZIKV
      strain. The sequence was identified from the brain tissue of an aborted fetus
      with microcephaly. The BAC clone was fully stable in bacteria and the infectious
      virus was efficiently recovered in Vero cells through direct delivery of the cDNA
      clone. The rescued virus yielded high titers in Vero cells and was pathogenic in
      a validated mouse model (A129 mice) of ZIKV infection. Furthermore, using this
      infectious clone we have generated a mutant ZIKV containing a single amino acid
      substitution (A175V) in the NS2A protein that presented reduced viral RNA
      synthesis in cell cultures, was highly attenuated in vivo and induced fully
      protection against a lethal challenge with ZIKV wild-type. This BAC approach
      provides a stable and reliable reverse genetic system for ZIKV that will help to
      identify viral determinants of virulence and facilitate the development of
      vaccine and therapeutic strategies.

PMID- 30301245
TI  - AWRK6, a Novel GLP-1 Receptor Agonist, Attenuates Diabetes by Stimulating Insulin
      Secretion.
AB  - Diabetes is a metabolic disorder leading to many complications. The treatment of
      diabetes mainly depends on hypoglycemic drugs, often with side effects, which
      drive us to develop novel agents. AWRK6 was a peptide developed from the
      antimicrobial peptide Dybowskin-2CDYa in our previous study, and the availability
      of AWRK6 on diabetes intervention was unknown. Here, in vivo and in vitro
      experiments were carried out to investigate the effects of AWRK6 against
      diabetes. In diabetic mice, induced by high-fat diet followed by streptozocin
      (STZ) administration, the daily administration of AWRK6 presented acute and
      sustained hypoglycemic effects. The plasma insulin was significantly elevated by
      AWRK6 during an oral glucose tolerance test (OGTT). The relative beta cell mass
      in diabetic mice was increased by AWRK6 treatment. The body weight and food
      intake were remarkably reduced by AWRK6 administration. In the mouse pancreatic
      beta cell line Min6 cells, the intracellular calcium concentration was found to
      be enhanced under the treatment with AWRK6, and protein kinase A (PKA) inhibitor
      H-89 and Epac2 inhibitor HJC0350 represented inhibitory effects of the
      insulinotropic function of AWRK6. By FITC-AWRK6 incubation and GLP-1 receptor
      (GLP-1R) knockdown, AWRK6 proved to be a novel GLP-1R agonist. In addition, AWRK6
      showed no toxicity in cell viability and membrane integrity in Min6 cells, and no
      hypoglycemia risk and no lethal toxicity in mice. In summary, AWRK6 was found as
      a novel agonist of GLP-1R, which could stimulate insulin secretion to regulate
      blood glucose and energy metabolism, via cAMP-calcium signaling pathway, without
      significant toxicity. The peptide AWRK6 might become a novel candidate for
      diabetes treatment.

PMID- 30301246
TI  - Cycle Stability and Hydration Behavior of Magnesium Oxide and Its Dependence on
      the Precursor-Related Particle Morphology.
AB  - Thermochemical energy storage is considered as an auspicious method for the
      recycling of medium-temperature waste heat. The reaction couple Mg(OH)2-MgO is
      intensely investigated for this purpose, suffering so far from limited cycle
      stability. To overcome this issue, Mg(OH)2, MgCO3, and MgC2O4.2H2O were compared
      as precursor materials for MgO production. Depending on the precursor, the
      particle morphology of the resulting MgO changes, resulting in different
      hydration behavior and cycle stability. Agglomeration of the material during
      cyclization was identified as main reason for the decreased reactivity. Immersion
      of the spent material in liquid H2O decomposes the agglomerates restoring the
      initial reactivity of the material, thus serving as a regeneration step.

PMID- 30301247
TI  - Dietary Intake of Vitamin D in the Czech Population: A Comparison with Dietary
      Reference Values, Main Food Sources Identified by a Total Diet Study.
AB  - The usual dietary intake of vitamin D was studied in 10 subgroups of the Czech
      population. Food consumption data was collected using repeated 24 h recall in a
      national cross-sectional survey (the Study of Individual Food Consumption,
      SISP04), and the vitamin D content in marketed foods was quantified within the
      national Total Diet Study (2014-2015). The Monte Carlo Risk Assessment
      computational model (version MCRA 8.2) was used to assess usual intake. The
      median vitamin D intakes for the Czech population (aged 4-90 years, both genders)
      were within a range of 2.5-5.1 MUg/day. The highest median intake, excluding
      dietary supplements, was observed in men aged 18-64, and the lowest was observed
      in children aged 4-6 and girls aged 11-17. The main sources in the diet were hen
      eggs (21-28% of usual dietary intake), fine bakery wares (11-19%), cow's milk and
      dairy products (7-23%), meat and meat products (4-12%), fish (6-20%), and
      margarines (7-18%). The dietary intake of vitamin D for more than 95% of the
      Czech population was below the recommended Dietary Reference Values (DRVs). These
      findings should encourage public health authorities to support interventions and
      education and implement new regulatory measures for improving intake.

PMID- 30301248
TI  - Electrochemical Measurements of Multiwalled Carbon Nanotubes under Different
      Plasma Treatments.
AB  - In the present work, we described the post-treatment effects of applying
      different plasma atmosphere conditions on the electrochemical performances of the
      multiwalled carbon nanotubes (MWCNTs). For the study, a composite of MWCNTs/Co/Ti
      was successfully grown on the silicon substrate and then pre-treated with
      ammonia, oxygen and hydrogen plasma. The composite was characterized by making
      use of field emission scanning electron microscopy (FESEM) for the surface
      morphology and Raman spectroscopy for the functionalization. Further, the
      electrochemical measurements were performed with the use of the cyclic
      voltammetry (CV) applied in the 0.01 M potassium ferricyanide in 0.1 M KCl
      solution. On testing, the results indicated that the NH3-treated MWCNTs have the
      highest efficiency as compared to the other pretreatments and control. This
      increased performance of NH3 treated sample can be linked to the enhanced surface
      area of the composite, thereby improved adsorption and associated interaction
      with that of the analyte molecules at the electrodes. Further comparison of the
      electrode with that of commercial Dropsens electrodes provided the confirmation
      for the efficiency of the NH3/MWCNTs, thereby suggesting for the potentiality of
      applying the NH3 modified electrode towards electrochemical applications.

PMID- 30301249
TI  - IMU-Based Virtual Road Profile Sensor for Vehicle Localization.
AB  - A road profile can be a good reference feature for vehicle localization when a
      Global Positioning System signal is unavailable. However, cost effective and
      compact devices measuring road profiles are not available for production
      vehicles. This paper presents a longitudinal road profile estimation method as a
      virtual sensor for vehicle localization without using bulky and expensive sensor
      systems. An inertial measurement unit installed in the vehicle provides filtered
      signals of the vehicle's responses to the longitudinal road profile. A
      disturbance observer was designed to extract the characteristic features of the
      road profile from the signals measured by the inertial measurement unit. Design
      synthesis based on a Kalman filter was used for the observer design. A nonlinear
      damper is explicitly considered to improve the estimation accuracy. Virtual
      measurement signals are introduced for observability. The suggested methodology
      estimates the road profile that is sufficiently accurate for localization. Based
      on the estimated longitudinal road profile, we generated spectrogram plots as the
      features for localization. The localization is realized by matching the
      spectrogram plot with pre-indexed plots. The localization using the estimated
      road profile shows a few meters accuracy, suggesting a possible road profile
      estimation method as an alternative sensor for vehicle localization.

PMID- 30301250
TI  - Misperception of Oral Health among Adults in Rural Areas: A Fundamental but
      Neglected Issue in Primary Healthcare.
AB  - Background: Poor oral hygiene is associated with metabolic syndrome, systemic
      diseases, mortality and many chronic diseases. Misperception means a wrong or
      incorrect understanding or interpretation. Few studies have examined the
      subjective perception and objective condition of oral health among community
      adults in rural areas. Methods: This was a cross-sectional, community-based
      study. Participants were recruited via convenience samples from December 2015 to
      July 2016. One thousand six (1006) community residents participated in the
      project, of which 973 fulfilled the inclusion criteria. The average age was 42.8
      (SD = 12.3) years, range 20-64, selected from a collaboration local hospital.
      Results: Most of the participants reported brushing their teeth every day,
      however, 72% reported seldom brushing their teeth after meals, 54% seldom used
      dental floss, 64% seldom received dental scaling, 29.5% had experienced a
      toothache within 6 months, and 30.5% demonstrated significant tooth loss.
      However, most of them perceived their oral health as good. Misperception of oral
      health was common, 21.5% among whose number of remaining teeth <25 under-assess
      their actual oral health. The more number of remaining teeth (p < 0.001) and
      regular dental check-up (p < 0.01) were positively associated with feeling good
      about their oral health. After adjusting for potential confounders, clinically
      significant findings indicated that number of remaining teeth (OR = 3.03, p <
      0.001), age (OR = 0.99, p < 0.001), regular dental check-ups/scaling (OR = 1.85,
      p < 0.001), education (OR = 1.45, p < 0.05), and water consumption (OR = 1.38, p
      < 0.05) were independently associated with good perceived oral health.
      Conclusions: The findings showed that subjective self-perception of oral health
      was not matched with their objective oral condition. Excluding the unmodifiable
      factors, the clinical implications indicated that oral health promotion programs,
      particularly for adopting regular dental check-up, healthy diet and oral hygiene
      habits are urgent in rural areas.

PMID- 30301251
TI  - Development and Validation of a New Tool to Assess Burden of Dietary Sodium
      Restriction in Patients with Chronic Heart Failure: The BIRD Questionnaire.
AB  - (1) Background: Burden scales are useful in estimating the impact of
      interventions from patients' perspectives. This is overlooked in sodium
      diet/heart failure (HF). The aim of this study is to develop and validate a
      specific tool to assess the burden associated with low-sodium diets in HF: the
      Burden scale In Restricted Diets (BIRD). (2) Methods: Based on the literature and
      reports from patients, 14 candidate items were identified for the following
      dietary-related domains: organization, pleasure, leisure, social life, vitality,
      and self-rated health. The validation study was conducted prospectively. The
      questionnaire was refined via item reduction according to inter-item correlations
      and exploratory factor analysis. Internal consistency was determined using
      Cronbach's alpha (Calpha) and convergent validity by assessing correlations
      between BIRD and the health-related quality of life (HRQoL) Minnesota Living with
      HF questionnaire (MLHF). (3) Results: Of the 152 invited patients, 96 (63%)
      returned the questionnaire. The median score was 6.5 (IQR 2.0-14.0). The results
      showed good acceptability (non-response rates/item from 2.0% to 12.1%), an
      excellent internal consistency (Calpha = 0.903) and a good convergent validity
      (rhos = 0.37 (physical), 0.4 (mental), and 0.45 (global); all p < 0.05). (4)
      Conclusions: BIRD demonstrates good psychometric properties and is useful to
      quantify the burden associated with sodium restriction. It may help optimize
      dietary interventions and improve the overall management of patients with HF.

PMID- 30301253
TI  - Cost-Effective Biochar Produced from Agricultural Residues and Its Application
      for Preparation of High Performance Form-Stable Phase Change Material via Simple
      Method.
AB  - A new form-stable composite phase change material (PEG/ASB) composed of almond
      shell biochar (ASB) and polyethylene glycol (PEG) was produced via a simple and
      easy vacuum impregnation method. The supporting material ASB, which was cost
      effective, environmentally friendly, renewable and rich in appropriate pore
      structures, was produced from agricultural residues of almond shells by a simple
      pyrolysis method, and it was firstly used as the matrix of PEG. Different
      analysis techniques were applied to investigate the characteristics of PEG/ASB,
      including structural and thermal properties, and the interaction mechanism
      between ASB and PEG was studied. The thermogravimetric analysis (TGA) and thermal
      cycle tests demonstrated that PEG/ASB possessed favorable thermal stability. The
      differential scanning calorimetry (DSC) curves demonstrated that the capacities
      for latent heat storage of PEG/ASB were enhanced with increasing PEG weight
      percentage. Additionally, PEG/ASB had an excellent thermal conductivity of 0.402
      W/mK, which was approximately 1.6 times higher than that of the pure PEG due to
      the addition of ASB. All the study results indicated that PEG/ASB had favorable
      phase change properties, which could be used for thermal energy storage.

PMID- 30301252
TI  - Stereotactic Radiosurgery and Immune Checkpoint Inhibitors in the Management of
      Brain Metastases.
AB  - Brain metastases traditionally carried a poor prognosis with an overall survival
      of weeks to months in the absence of treatment. Radiation therapy modalities
      include whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS).
      WBRT delivers a relatively low dose of radiation, has neurocognitive sequelae,
      and has not been investigated for its immunostimulatory effects. Furthermore,
      WBRT exposes the entire intracranial tumor immune microenvironment to radiation.
      SRS delivers a high dose of conformal radiation with image guidance to minimize
      dose to surrounding normal brain tissue, and appears to promote anti-tumor
      immunity. In parallel with many of these discoveries, immune checkpoint
      inhibitors (ICIs) have demonstrated a survival advantage in multiple malignancies
      commonly associated with brain metastases (e.g., melanoma). Combination SRS and
      ICI are theorized to be synergistic in anti-tumor immunity directed to brain
      metastases. The purpose of this review is to explore the synergy of SRS and ICIs,
      including pre-clinical data, existing clinical data, and ongoing prospective
      trials.

PMID- 30301255
TI  - Grain Refinement by Second Phase Particles under Applied Stress in ZK60 Mg Alloy
      with Y through Phase Field Simulation.
AB  - Based on the principle of grain refinement caused by the second-phase particles,
      a phase field model was built to describe the recrystallization process in the
      ZK60 alloy system with Y added under applied stress between temperatures 573 and
      673 K for 140 min duration. The simulation of grain growth with second phase
      particles and applied stress during annealing process on industrial scale on the
      condition of real time-space was achieved. Quantitative analysis was carried out
      and some useful laws were revealed in ZK60 alloy system. The second phase
      particles had a promoting effect on the grain refinement, however the effect
      weakened significantly when the content exceeded 1.5%. Our simulation results
      reveal the existence of a critical range of second phase particle size of 0.3-0.4
      MUm, within which a microstructure of fine grains can be obtained. Applied stress
      increased the grain coarsening rate significantly when the stress was more than
      135 MPa. The critical size of the second phase particles was 0.4-0.75 MUm when
      the applied stress was 135 MPa. Finally, a microstructure with a grain size of
      11.8-13.8 MUm on average could be obtained when the second phase particles had a
      content of 1.5% and a size of 0.4-0.75 MUm with an applied stress less than 135
      Mpa after 30 min annealing at 573 K.

PMID- 30301254
TI  - The Inhibitory Effect of Flavonoid Aglycones on the Metabolic Activity of CYP3A4
      Enzyme.
AB  - Flavonoids are natural compounds that have been extensively studied due to their
      positive effects on human health. There are over 4000 flavonoids found in higher
      plants and their beneficial effects have been shown in vitro as well as in vivo.
      However, data on their pharmacokinetics and influence on metabolic enzymes is
      scarce. The aim of this study was to focus on possible interactions between the
      30 most commonly encountered flavonoid aglycones on the metabolic activity of
      CYP3A4 enzyme. 6beta-hydroxylation of testosterone was used as marker reaction of
      CYP3A4 activity. Generated product was determined by HPLC coupled with diode
      array detector. Metabolism and time dependence, as well as direct inhibition,
      were tested to determine if inhibition was reversible and/or irreversible. Out of
      the 30 flavonoids tested, 7 significantly inhibited CYP3A4, most prominent being
      acacetin that inhibited 95% of enzyme activity at 1 uM concentration. Apigenin
      showed reversible inhibition, acacetin, and chrysin showed combined irreversible
      and reversible inhibition while chrysin dimethylether, isorhamnetin, pinocembrin,
      and tangeretin showed pure irreversible inhibition. These results alert on
      possible flavonoid-drug interactions on the level of CYP3A4.

PMID- 30301256
TI  - Restoring Large Defect of Posterior Tooth by Indirect Composite Technique: A Case
      Report.
AB  - Advances in adhesive dentistry have led to increased use of indirect
      restorations. In some situations, indirect composite techniques are more
      advantageous than direct composite filling techniques, such as establishing
      proper occlusal and interproximal anatomy, reducing polymerization shrinkage
      stress, and promoting the degree of conversion. This article presents a case
      about restoring the lower right first molar with extensive loss of tooth
      structure by the composite onlay to achieve a proper anatomic form and
      rehabilitate chewing function. This one-year clinical case encourages clinicians
      to manage large decay of posterior tooth conservatively. The given functional and
      esthetic outcomes demonstrate the promising applicability of the indirect
      composite technique.

PMID- 30301257
TI  - Poisson's Ratio of Closed-Cell Aluminium Foams.
AB  - A nondestructive impulse excitation technique was used to investigate Poisson's
      ratio of powder metallurgical pure closed-cell aluminium foams according to ASTM
      E 1876 within the foam density range of 0.430-1.390 g.cm-3. Instead of a constant
      value of 0.34, as according to Gibson and Ashby's assumption for the Poisson's
      ratio of metallic foams, the decrease of the Poisson's ratio with decreasing foam
      density was observed. Observed Poisson's ratio data were in the range of 0.21
      0.34. To check the validity of the results, the Young's modulus was calculated
      using Poisson's ratio and its dependence on relative density was successfully
      modelled using the usual power law function with characteristic exponent of 1.72
      +/- 0.1. This confirms that the obtained experimental results for Poisson's ratio
      are valid. Finally, rule of mixture and percolation theory were used to model the
      observed decrease of Poisson's ratio with increasing porosity.

PMID- 30301258
TI  - LTCC Packaged Ring Oscillator Based Sensor for Evaluation of Cell Proliferation.
AB  - A complementary metal-oxide-semiconductor (CMOS) chip biosensor was developed for
      cell viability monitoring based on an array of capacitance sensors utilizing a
      ring oscillator. The chip was packaged in a low temperature co-fired ceramic
      (LTCC) module with a flip chip bonding technique. A microcontroller operates the
      chip, while the whole measurement system was controlled by PC. The developed
      biosensor was applied for measurement of the proliferation stage of adherent
      cells where the sensor response depends on the ratio between healthy, viable and
      multiplying cells, which adhere onto the chip surface, and necrotic or apoptotic
      cells, which detach from the chip surface. This change in cellular adhesion
      caused a change in the effective permittivity in the vicinity of the sensor
      element, which was sensed as a change in oscillation frequency of the ring
      oscillator. The sensor was tested with human lung epithelial cells (BEAS-2B)
      during cell addition, proliferation and migration, and finally detachment induced
      by trypsin protease treatment. The difference in sensor response with and without
      cells was measured as a frequency shift in the scale of 1.1 MHz from the base
      frequency of 57.2 MHz. Moreover, the number of cells in the sensor vicinity was
      directly proportional to the frequency shift.

PMID- 30301259
TI  - A Novel Tb@Sr-MOF as Self-Calibrating Luminescent Sensor for Nutritional
      Antioxidant.
AB  - Sesamol, is well-known antioxidant and can reduce the rate of oxidation and
      prolong expiration date. It is also potentially antimutagenic and
      antihepatotoxic, the detection of sesamol is important and remains a huge
      challenge. Herein, a new 3D alkaline earth Sr metal organic framework
      [Sr(BDC)DMACH2O]n (BDC = benzene-1,4-dicarboxylate; DMAC = N,N-dimethylacetamide)
      is synthesized and a probe based on Tb3+ functionalized Sr-MOF. The Tb(3+)@Sr-MOF
      showed good luminescence and thermal property. Due to the energy competition
      between sesamol and ligand, the luminescence intensity of sesamol increases
      meantime luminescence intensity of Tb3+ decreases, the ratio of the emission
      intensities (I344/I545) linearly increases with sesamol in concentrations ranging
      from 1 * 10-7 to 8 * 10-4 M. Furthermore, the fluorescence-detected circular test
      shows that the composite Tb(3+)@Sr-MOF can serve as ratiometric sensor for
      sensing of sesamol. This is the first example for self-calibrated detecting
      sesamol based on metal-organic framework (MOF).

PMID- 30301261
TI  - Operation Mechanism of a MoS2/BP Heterojunction FET.
AB  - The electrical characteristics and operation mechanism of a molybdenum
      disulfide/black phosphorus (MoS2/BP) heterojunction device are investigated
      herein. Even though this device showed a high on-off ratio of over 1 * 107, with
      a lower subthreshold swing of ~54 mV/dec and a 1fA level off current, its
      operating mechanism is closer to a junction field-effect transistor (FET) than a
      tunneling FET. The off-current of this device is governed by the depletion region
      in the BP layer, and the band-to-band tunneling current does not contribute to
      the rapid turn-on and extremely low off-current.

PMID- 30301260
TI  - Uremia Impacts VE-Cadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell
      Junctions.
AB  - Endothelial dysfunction in uremia can result in cell-to-cell junction loss and
      increased permeability, contributing to cardiovascular diseases (CVD)
      development. This study evaluated the impact of the uremic milieu on endothelial
      morphology and cell junction's proteins. We evaluated (i) serum levels of
      inflammatory biomarkers in a cohort of chronic kidney disease (CKD) patients and
      the expression of VE-cadherin and Zonula Occludens-1 (ZO-1) junction proteins on
      endothelial cells (ECs) of arteries removed from CKD patients during renal
      transplant; (ii) ECs morphology in vitro under different uremic conditions, and
      (iii) the impact of uremic toxins p-cresyl sulfate (PCS), indoxyl sulfate (IS),
      and inorganic phosphate (Pi) as well as of total uremic serum on VE-cadherin and
      ZO-1 gene and protein expression in cultured ECs. We found that the uremic
      arteries had lost their intact and continuous endothelial morphology, with a
      reduction in VE-cadherin and ZO-1 expression. In cultured ECs, both VE-cadherin
      and ZO-1 protein expression decreased, mainly after exposure to Pi and uremic
      serum groups. VE-cadherin mRNA expression was reduced while ZO-1 was increased
      after exposure to PCS, IS, Pi, and uremic serum. Our findings show that uremia
      alters cell-to-cell junctions leading to an increased endothelial damage. This
      gives a new perspective regarding the pathophysiological role of uremia in
      intercellular junctions and opens new avenues to improve cardiovascular outcomes
      in CKD patients.

PMID- 30301262
TI  - Genomic Deletion of BAP1 and CDKN2A Are Useful Markers for Quality Control of
      Malignant Pleural Mesothelioma (MPM) Primary Cultures.
AB  - Malignant pleural mesothelioma (MPM) is a deadly cancer that is caused by
      asbestos exposure and that has limited treatment options. The current standard of
      MPM diagnosis requires the testing of multiple immunohistochemical (IHC) markers
      on formalin-fixed paraffin-embedded tissue to differentiate MPM from other lung
      malignancies. To date, no single biomarker exists for definitive diagnosis of MPM
      due to the lack of specificity and sensitivity; therefore, there is ongoing
      research and development in order to identify alternative biomarkers for this
      purpose. In this study, we utilized primary MPM cell lines and tested the
      expression of clinically used biomarker panels, including CK8/18, Calretinin, CK
      5/6, CD141, HBME-1, WT-1, D2-40, EMA, CEA, TAG72, BG8, CD15, TTF-1, BAP1, and Ber
      Ep4. The genomic alteration of CDNK2A and BAP1 is common in MPM and has potential
      diagnostic value. Changes in CDKN2A and BAP1 genomic expression were confirmed in
      MPM samples in the current study using Fluorescence In situ Hybridization (FISH)
      analysis or copy number variation (CNV) analysis with digital droplet PCR
      (ddPCR). To determine whether MPM tissue and cell lines were comparable in terms
      of molecular alterations, IHC marker expression was analyzed in both sample
      types. The percentage of MPM biomarker levels showed variation between original
      tissue and matched cells established in culture. Genomic deletions of BAP1 and
      CDKN2A, however, showed consistent levels between the two. The data from this
      study suggest that genomic deletion analysis may provide more accurate biomarker
      options for MPM diagnosis.

PMID- 30301263
TI  - Segmentation and Multi-Scale Convolutional Neural Network-Based Classification of
      Airborne Laser Scanner Data.
AB  - The classification of point clouds is a basic task in airborne laser scanning
      (ALS) point cloud processing. It is quite a challenge when facing complex
      observed scenes and irregular point distributions. In order to reduce the
      computational burden of the point-based classification method and improve the
      classification accuracy, we present a segmentation and multi-scale convolutional
      neural network-based classification method. Firstly, a three-step region-growing
      segmentation method was proposed to reduce both under-segmentation and over
      segmentation. Then, a feature image generation method was used to transform the
      3D neighborhood features of a point into a 2D image. Finally, feature images were
      treated as the input of a multi-scale convolutional neural network for training
      and testing tasks. In order to obtain performance comparisons with existing
      approaches, we evaluated our framework using the International Society for
      Photogrammetry and Remote Sensing Working Groups II/4 (ISPRS WG II/4) 3D labeling
      benchmark tests. The experiment result, which achieved 84.9% overall accuracy and
      69.2% of average F1 scores, has a satisfactory performance over all participating
      approaches analyzed.

PMID- 30301265
TI  - Precision Motion Control of a Linear Permanent Magnet Synchronous Machine Based
      on Linear Optical-Ruler Sensor and Hall Sensor.
AB  - The linear optical-ruler sensor with 1um precision mounted in the linear
      permanent magnet synchronous machine (LPMSM) is used for measuring the mover
      position of LPMSM in order to enhance the precision of a measured mover position.
      Due to nonlinear friction and uncertainty effects, linear controllers are very
      hard to achieve good mover positioning of LPMSM. The proposed adaptive amended
      Elman neural network backstepping (AAENNB) control system is adopted for
      controlling the LPMSM drive system to bring about the mover positioning precision
      of LPMSM. Firstly, a backstepping scheme is posed for controlling the tracing
      motion of the LPMSM drive system. The proposed backstepping control system, which
      is applied in the mover position of the LPMSM drive system, possesses better
      dynamic control performance and robustness to uncertainties for the tracing
      trajectories. Because of the LPMSM with nonlinear and time-varying dynamic
      characteristics, an adaptive amended Elman neural network uncertainty observer
      (AAENNUO) is posed to estimate the required lumped uncertainty. According to the
      Lyapunov stability theorem, on-line parameter training methodology of the amended
      Elman neural network (AENN) can be derived by use of adaptive law. The error
      estimated law is proposed to compensate for the observed error induced by the
      AENN with adaptive law. Furthermore, to help improve convergence and to obtain
      better learning performance, the mended particle swarm optimization (PSO)
      algorithm is utilized for adjusting the varied learning rate of the weights in
      the AENN. At last, these experimental results, which show better performance, are
      verified by the proposed control system.

PMID- 30301264
TI  - Synthesis and Biological Evaluation of Novel Indole-Derived Thioureas.
AB  - A series of 2-(1H-indol-3-yl)ethylthiourea derivatives were prepared by
      condensation of 2-(1H-indol-3-yl)ethanamine with appropriate
      aryl/alkylisothiocyanates in anhydrous media. The structures of the newly
      synthesized compounds were confirmed by spectroscopic analysis and the molecular
      structures of 8 and 28 were confirmed by X-ray crystallography. All obtained
      compounds were tested for antimicrobial activity against Gram-positive cocci,
      Gram-negative rods and for antifungal activity. Microbiological evaluation was
      carried out over 20 standard strains and 30 hospital strains. Compound 6 showed
      significant inhibition against Gram-positive cocci and had inhibitory effect on
      the S. aureus topoisomerase IV decatenation activity and S. aureus DNA gyrase
      supercoiling activity. Compounds were tested for cytotoxicity and antiviral
      activity against a large panel of DNA and RNA viruses, including HIV-1 and other
      several important human pathogens. Interestingly, derivative 8 showed potent
      activity against HIV-1 wild type and variants bearing clinically relevant
      mutations. Newly synthesized tryptamine derivatives showed also a wide spectrum
      activity, proving to be active against positive- and negative-sense RNA viruses.

PMID- 30301266
TI  - Widely Linear Adaptive Instantaneous Frequency Estimation in Vector Hydrophones.
AB  - To solve the problem that the time-frequency resolution of Short-Time Fourier
      Transform (STFT) is constrained by the window length and the moving step of the
      short time window, and to utilize the merits of a widely linear method, a novel
      instantaneous frequency estimation method in vector hydrophone was proposed. In
      this paper, a complex variable was constructed. It is composed of sound pressure
      and particle velocity as its real part and imaginary part, respectively. The
      constructed variable was approved to be second order noncircular (improper). For
      the modelling of noncircular signals, the standard linear estimation is not
      adequate and the pseudo-covariance matrix should also be taken into
      consideration. As a result, a widely linear adaptive instantaneous frequency
      estimation algorithm and its three solutions based on the augmented complex least
      mean square (ACLMS) method are presented to estimate the instantaneous frequency
      in vector hydrophones. The results of simulations and laboratory experiments
      prove that this approach based on a widely linear model performs better compared
      to STFT and strict linear filter methods.

PMID- 30301267
TI  - Citrus aurantium L. and Its Flavonoids Regulate TNBS-Induced Inflammatory Bowel
      Disease through Anti-Inflammation and Suppressing Isolated Jejunum Contraction.
AB  - Inflammatory bowel disease (IBD) is a serious digestive system disease, for which
      the clinical therapeutic choices remain limited. Dried fruits of Citrus aurantium
      L. (CAL) are a traditional medicine used for regulation of the digestive system.
      The aim of this study was to identify the regulatory effects of CAL on IBD and to
      clarify the mechanism of the active compounds. In trinitrobenzene sulfonic acid
      induced IBD rats, 125 to 500 mg/kg of oral CAL significantly alleviated weight
      loss and diarrhea, decreased colitis inflammatory cell infiltration, and
      inhibited pro-inflammatory cytokine production. The mechanisms of characteristic
      flavonoids in CAL were evaluated involving inflammation and intestine contraction
      aspects. Naringenin, nobiletin, and hesperetin showed anti-inflammatory effects
      on lipopolysaccharide-induced RAW cells. The mechanism may be related to the
      inhibition of the tumor necrosis factor-alpha (TNF-alpha)-induced nuclear factor
      kappa-light-chain-enhancer of activated B cells (NF-kappaB) pathway to suppress
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions.
      Naringenin and nobiletin showed inhibitory effects on isolated jejunum
      contraction. The mechanism of naringenin is partly related to COX, NOS, inositol
      triphosphate (IP3), and finally, to decreased jejunum motility. This study
      demonstrated that CAL, and its flavonoids' regulatory effects on IBD through anti
      inflammation and inhibition of intestine muscle contraction, can provide basic
      information on developing new drugs or supplements against IBD based on CAL.

PMID- 30301268
TI  - Job Satisfaction and Perceived Health in Spanish Construction Workers during the
      Economic Crisis.
AB  - The attitude towards work, either satisfaction or dissatisfaction, could
      influence the way in which workers perceive their health status. To check this
      hypothesis, this study analyses job satisfaction and its relationship with
      occupational health perception of Spanish construction workers. A descriptive,
      cross-sectional, observational study was carried out through a socio-demographic
      data questionnaire, the General Scale of Job Satisfaction and the SF-36 Health
      Survey. The study was conducted from January 2014 to June 2015, on a sample of
      302 individuals belonging to Andalusian companies using the stratified random
      method to access companies from different provinces and sizes. The findings
      indicate that work experience in the sector increases general satisfaction:
      workers above 55 years of age are more satisfied with their work than those
      between 36 and 45. Likewise, workers with an experience of 2-5 years show higher
      levels of overall satisfaction, in opposition to workers with 6 months and 2
      years of experience. On the other hand, workers without a contract and interns
      are the most dissatisfied in job terms. Also, there is a positive correlation
      between job satisfaction and the positive dimensions of health perception
      (physical functioning and physical and social role functioning), as well as a
      negative correlation between job satisfaction and bodily pain and general health
      perceived.

PMID- 30301269
TI  - Resveratrol Attenuates Staphylococcus Aureus-Induced Monocyte Adhesion through
      Downregulating PDGFR/AP-1 Activation in Human Lung Epithelial Cells.
AB  - Staphylococcus aureus (S. aureus) is a very common Gram-positive bacterium. It is
      widely distributed in air, soil, and water. S. aureus often causes septicemia and
      pneumonia in patients. In addition, it is considered to play a key role in
      mediating cell adhesion molecules upregulation. Resveratrol is a natural
      antioxidant with diverse biological effects, including the modulation of immune
      function, anti-inflammation, and cancer chemoprevention. In this study, we proved
      that S. aureus-upregulated vascular cell adhesion molecule-1 (VCAM-1) expression
      in human lung epithelial cells (HPAEpiCs) was inhibited by resveratrol. We also
      observed that resveratrol downregulated S. aureus-enhanced leukocyte count in
      bronchoalveolar lavage (BAL) fluid in mice. In HPAEpiCs, S. aureus stimulated c
      Src, PDGFR, p38 MAPK, or JNK1/2 phosphorylation, which was inhibited by
      resveratrol. S. aureus induced the adhesion of THP-1 cells (a human monocytic
      cell line) to HPAEpiCs, which was also reduced by resveratrol. Finally, we found
      that S. aureus induced c-Src/PDGFR/p38 MAPK and JNK1/2-dependent c-Jun and ATF2
      activation and in vivo binding of c-Jun and ATF2 to the VCAM-1 promoter, which
      were inhibited by resveratrol. Thus, resveratrol functions as a suppressor of S.
      aureus-induced inflammatory signaling, not only by inhibiting VCAM-1 expression
      but also by diminishing c-Src, PDGFR, JNK1/2, p38 MAPK, and AP-1 activation in
      HPAEpiCs.

PMID- 30301270
TI  - In Vivo Evaluation of Antirrhinum majus' Wound-Healing Activity.
AB  - Mediterranean-native perennial plant Antirrhinum majus was scrutinized in this
      study for its antioxidant activity and its total phenolic content in order to
      test for the plant's wound-healing capability. The traditional uses of this plant
      to treat gum scurvy, various tumors, ulcers, and hemorrhoids were the main idea
      behind this study. Leaves and flowers of the A. majus were extracted by
      maceration. Pilot qualitative phytochemical tests were made to check the presence
      of various secondary metabolites. Quantitatively, the flowers' macerate indicated
      superlative results regarding antioxidant activity and total phenolic content.
      However, the in vivo wound-healing capability study was made using 30 Wistar
      strain albino rats. This innovative part of the study revealed that the healing
      power of the flowers' extract ointment (5% w/w) was superior compared to the
      leaves' extract (5% w/w) and the positive-control ointments (MEBO) (1.5% w/w) (p
      <= 0.001). This activity was assessed by visual examination, wound-length
      measurement, and estimation of hydroxyproline content. Antirrhinum majus is a
      promising plant to be considered for wound healing. However, further testing
      (including histological examination and high-performance liquid chromatography
      (HPLC) analysis) is necessary to understand more about its mechanisms of action.

PMID- 30301272
TI  - Comparison of Perceived and Observed Hand Hygiene Compliance in Healthcare
      Workers in MERS-CoV Endemic Regions.
AB  - This study investigated healthcare workers' perceptions of hand hygiene practices
      by comparing personal reports, as assessed by questionnaires, to direct
      observations of the workers' hand hygiene practices. The study employed a cross
      sectional research design. Observations were made using a 16-item checklist,
      based on three sources: Centers for Disease Control and Prevention (CDC), World
      Health Organization (WHO), and Boyce and Pittet's guidelines of hand hygiene. The
      checklist was used for both direct-observation and self-reported data collection
      purposes. Pearson correlation and Multivariate Analysis of Covariance (MANCOVA)
      were utilized to statistically determine the relationship between healthcare
      workers' reports of hand hygiene practices and observed hand hygiene behaviors.
      The study was conducted in the outpatient examination rooms and emergency
      departments of three types of hospitals in the Eastern region of Saudi Arabia
      where Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic and is
      observed in routine cases and outbreaks. The total sample size included 87
      physicians and nurses recruited while on duty during the scheduled observation
      periods, with each healthcare worker being observed during individual medical
      examinations with at least three patients. No statistically significant
      correlations between the healthcare workers' perceptions of hand hygiene
      practices and healthcare workers' actual behaviors were evident. Based on the
      self-report questionnaires, significant differences were found between
      physicians' and nurses' hand hygiene practices reports. Healthcare workers
      clearly understand the importance of careful hand hygiene practices, but based on
      researchers' observations, the medical personnel failed to properly implement
      protocol-driven hand hygiene applications. However, the significant differences
      between physicians' and nurses' self-reports suggest further inquiry is needed to
      fully explore these discrepancies.

PMID- 30301271
TI  - Enhancing Skin Health: By Oral Administration of Natural Compounds and Minerals
      with Implications to the Dermal Microbiome.
AB  - The history of cosmetics goes back to early Egyptian times for hygiene and health
      benefits while the history of topical applications that provide a medicinal
      treatment to combat dermal aging is relatively new. For example, the term
      cosmeceutical was first coined by Albert Kligman in 1984 to describe topical
      products that afford both cosmetic and therapeutic benefits. However, beauty
      comes from the inside. Therefore, for some time scientists have considered how
      nutrition reflects healthy skin and the aging process. The more recent link
      between nutrition and skin aging began in earnest around the year 2000 with the
      demonstrated increase in peer-reviewed scientific journal reports on this topic
      that included biochemical and molecular mechanisms of action. Thus, the
      application of: (a) topical administration from outside into the skin and (b)
      inside by oral consumption of nutritionals to the outer skin layers is now common
      place and many journal reports exhibit significant improvement for both on a
      variety of dermal parameters. Therefore, this review covers, where applicable,
      the history, chemical structure, and sources such as biological and biomedical
      properties in the skin along with animal and clinical data on the oral
      applications of: (a) collagen, (b) ceramide, (c) beta-carotene, (d) astaxanthin,
      (e) coenzyme Q10, (f) colostrum, (g) zinc, and (h) selenium in their mode of
      action or function in improving dermal health by various quantified endpoints.
      Lastly, the importance of the human skin microbiome is briefly discussed in
      reference to the genomics, measurement, and factors influencing its expression
      and how it may alter the immune system, various dermal disorders, and potentially
      be involved in chemoprevention.

PMID- 30301274
TI  - Granulin A Synergizes with Cisplatin to Inhibit the Growth of Human
      Hepatocellular Carcinoma.
AB  - Cisplatin is one of the most potent chemotherapy drugs widely used for cancer
      treatment. However, due to resistance and toxicity, the application of cisplatin
      for the treatment of hepatocellular carcinoma (HCC) is limited. Our previous
      study has shown that granulin A (GRN A), an anticancer peptide, is able to
      interact with enolase1 (ENO1) and inhibit the growth of HCC in vitro. In the
      present study, we studied the synergistic effect of the combination of cisplatin
      and GRN A for the inhibitory effect on HCC. An 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and Chou
      Talalay approaches revealed that the combination of GRN A and cisplatin displayed
      potent synergistic effect. The colony formation and cell viability of HCC cells
      were inhibited significantly in cells treated with the combination of cisplatin
      and GRN A, compared with cells treated with cisplatin or GRN A alone.
      Overexpression of ENO1 diminished the synergistic effect of GRN A and cisplatin
      in HCC cells. The combination of the two drugs exhibited a more obvious
      inhibitory effect on cancer cell apoptosis, as analyzed by the cytometry flow,
      mitochondrial membrane potential (MMP) and western blot analysis. An in vivo
      study confirmed that the combined use of the two drugs displayed more potent
      antitumor activity compared to mice treated with cisplatin and GRN A alone; the
      inhibitory rate of tumor growth was 65.46% and 68.94%, respectively, in mice
      treated with GRN A and cisplatin. However, the inhibitory rate increased to
      86.63% in mice treated with the combination of the two drugs. This study provides
      evidence that the combination of GRN A and cisplatin is able to sensitize the
      liver cancer to cisplatin, and that targeting ENO1 is a promising approach for
      enhancing the antitumor activity of cisplatin.

PMID- 30301275
TI  - Applications of Ion Mobility-Mass Spectrometry in Carbohydrate Chemistry and
      Glycobiology.
AB  - Carbohydrate analyses are often challenging due to the structural complexity of
      these molecules, as well as the lack of suitable analytical tools for
      distinguishing the vast number of possible isomers. The coupled technique, ion
      mobility-mass spectrometry (IM-MS), has been in use for two decades for the
      analysis of complex biomolecules, and in recent years it has emerged as a
      powerful technique for the analysis of carbohydrates. For carbohydrates, most
      studies have focused on the separation and characterization of isomers in
      biological samples. IM-MS is capable of separating isomeric ions by drift time,
      and further characterizing them by mass analysis. Applications of IM-MS in
      carbohydrate analysis are extremely useful and important for understanding many
      biological mechanisms and for the determination of disease states, although
      efforts are still needed for higher sensitivity and resolution.

PMID- 30301273
TI  - Zinc Finger Readers of Methylated DNA.
AB  - DNA methylation is a prevalent epigenetic modification involved in regulating a
      number of essential cellular processes, including genomic accessibility and
      transcriptional outcomes. As such, aberrant alterations in global DNA methylation
      patterns have been associated with a growing number of disease conditions.
      Nevertheless, the full mechanisms by which DNA methylation information is
      interpreted and translated into genomic responses is not yet fully understood.
      Methyl-CpG binding proteins (MBPs) function as important mediators of this
      essential process by selectively reading DNA methylation signals and translating
      this information into down-stream cellular outcomes. The Cys2His2 zinc finger
      scaffold is one of the most abundant DNA binding motifs found within human
      transcription factors, yet only a few zinc finger containing proteins capable of
      conferring selectivity for mCpG over CpG sites have been characterized. This
      review summarizes our current structural understanding for the mechanisms by
      which the zinc finger MBPs evaluated to date read this essential epigenetic mark.
      Further, some of the biological implications for mCpG readout elicited by this
      family of MBPs are discussed.

PMID- 30301276
TI  - Impact of Blood or Erythrocyte Membrane Fatty Acids for Disease Risk Prediction:
      Focusing on Cardiovascular Disease and Chronic Kidney Disease.
AB  - Fatty acids (FAs) are essential nutrients and main constituents of cell membranes
      that are involved in the signaling pathway and associated with health conditions.
      We investigated if blood or erythrocyte membrane FAs can predict the risk of
      cardiovascular disease (CVD), chronic kidney disease (CKD), and related
      complications. Omega-3 (n-3) FAs are important predictors for metabolic syndrome,
      diabetes, CVD, and CKD risks, and the n-3 index is also a good biomarker for
      sudden cardiac death in coronary artery disease. Linoleic acid, which is one of
      the major n-6 FAs reflecting recent dietary FA intake, may predict CVD risk and
      mortality in the general population and patients with CKD. Monounsaturated FAs
      (MUFAs) are also related to diabetes or diabetic nephropathy. Oleic acid, a major
      MUFA, is an emerging marker that is related to acute coronary syndrome, low
      glomerular filtration rate, and vascular calcification in patients with CKD, and
      can be modified by n-3 FA supplementation. Saturated FAs, trans-FAs, and FA
      desaturation/elongation are associated with CVD risk; however, few studies have
      been conducted on patients with CKD. In summary, blood or erythrocyte membrane FA
      measurements are important for CVD and CKD risk prediction and management.
      Further studies are needed to elucidate the FAs for their risk predictions.

PMID- 30301279
TI  - Examining the Effect of Radiant Exposure on Commercial Photopolimerizable Dental
      Resin Composites.
AB  - The objective of this study was to evaluate the effect of radiant exposure on the
      chemical and physical properties of four commercial dental resin composites. The
      four dental resin composites used were Kalore, Admira, Tetric N-Ceram Bulk Fill,
      and Filtek Z350 XT. The composites were subjected to three curing protocols: 1000
      mW/cm2 for 5 s, 1000 mW/cm2 for 10 s, and 400 mW/cm2 for 25 s. The flexural
      strength, elastic modulus, water sorption, water solubility, degree of
      conversion, and polymerization shrinkage were evaluated. The results were
      analyzed by means of ANOVA and Tukey tests. For Admira and Kalore, significant
      differences between light exposure protocols were observed for the elastic
      modulus (p < 0.001), which was higher when a higher amount of radiant exposure
      was used. For Filtek Z350, differences were only observed for the degree of
      conversion (p < 0.001), and a higher amount of radiant exposure allowed us to
      obtain higher values. The Tetric N-Ceram Bulk Fill analysis showed significant
      differences for the elastic modulus and water sorption (p < 0.001), and specimens
      that had been subject to a radiant exposure of 10 J/cm2 showed a higher elastic
      modulus. In most cases, the physical and mechanical properties analyzed were not
      affected by different radiant exposure values. Other resin-based composite (RBC)
      characteristics seem to have a greater influence on material properties.

PMID- 30301277
TI  - Synthesis and Biological Evaluation of Thalidomide Derivatives as Potential Anti
      Psoriasis Agents.
AB  - Several thalidomide derivatives were synthesized and evaluated for their anti
      inflammatory activity. Introduction of the benzyl group to the parent thalidomide
      is unfavorable in which 2-(1-benzyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione
      (4a) was inactivated. However, the inhibitory activities on TNF-alpha and IL-6
      expression in HaCaT cells were improved by the substitution of a chloro- or
      methoxy- group at the phenyl position of 4a. The IL-6 inhibitory activity
      decreased in an order of 5c (69.44%) > 4c (48.73%) > 6c (3.19%) indicating the 3
      substituted derivative is more active than the 4-substituted counterpart, which
      in turn is more active than the 2-substituted counterpart. Among them, 2-[1-(3
      chlorobenzyl)-2,6-dioxopiperidin-3-yl]isoindoline-1,3-dione (5c) was found to
      inhibit TNF-alpha and IL-6 expression in HaCaT cells with a higher potency than
      thalidomide and no significant cell cytotoxicity was detected at 10 MUM. In
      psoriasis, Compound 5c reduced IL-6, IL-8, IL-1beta and IL-24 in imiquimod
      stimulated models. Our results indicated that compound 5c is a potential lead of
      novel anti-psoriasis agents. Structural optimization of compound 5c and its in
      vivo assay are ongoing.

PMID- 30301278
TI  - Passive Sampling of Gaseous Elemental Mercury Based on a Composite TiO2NP/AuNP
      Layer.
AB  - Passive sampling systems (PASs) are a low cost strategy to quantify Hg levels in
      air over both different environmental locations and time periods of few hours to
      weeks/months. For this reason, novel nanostructured materials have been designed
      and developed. They consist of an adsorbent layer made of titania nanoparticles
      (TiO2NPs, <=25 nm diameter) finely decorated with gold nanoparticles. The TiO2NPs
      functionalization occurred for the photocatalytic properties of titania-anatase
      when UV-irradiated in an aqueous solution containing HAuCl4. The resulting
      nanostructured suspension was deposited by drop-casting on a thin quartz slices,
      dried and then incorporated into a common axial sampler to be investigated as a
      potential PAS device. The morphological characteristics of the sample were
      studied by High-Resolution Transmission Electron Microscopy, Atomic Force
      Microscopy, and Optical Microscopy. UV-Vis spectra showed a blue shift of the
      membrane when exposed to Hg0 vapors. The adsorbed mercury was thermally desorbed
      for a few minutes, and then quantified by a mercury vapor analyzer. Such a
      sampling system reported an efficiency of adsorption that was equal to ~95%.
      Temperature and relative humidity only mildly affected the membrane performances.
      These structures seem to be promising candidates for mercury samplers, due to
      both the strong affinity of gold with Hg, and the wide adsorbing surface.

PMID- 30301281
TI  - Smartphone Heading Correction Based on Gravity Assisted and Middle Time Simulated
      Zero Velocity Update Method.
AB  - Electronic appliances and ferromagnetic materials can be easily found in any
      building in urban environment. A steady magnetic environment and a pure value of
      geomagnetic field for calculating the heading of the smartphone in case of
      pedestrian walking indoors is hard to obtain. Therefore, an independent inertial
      heading correction algorithm without involving magnetic field but only making
      full use of the embedded Micro-Electro-Mechanical System (MEMS) Inertial
      measurement unit (IMU) device in the smartphone is presented in this paper.
      Aiming at the strict navigation requirements of pedestrian smartphone
      positioning, the algorithm focused in this paper consists of Gravity Assisted
      (GA) and Middle Time Simulated-Zero Velocity Update (MTS-ZUPT) methods. With the
      help of GA method, the different using-mode of the smartphone can be judged based
      on the data from the gravity sensor of smartphone. Since there is no zero
      velocity status for handheld smartphone, the MTS-ZUPT algorithm is proposed based
      on the idea of Zero Velocity Update (ZUPT) algorithm. A Kalman Filtering
      algorithm is used to restrain the heading divergence at the middle moment of two
      steps. The walking experimental results indicate that the MTS-ZUPT algorithm can
      effectively restrain the heading error diffusion without the assistance of
      geomagnetic heading. When the MTS-ZUPT method was integrated with GA method, the
      smartphone navigation system can autonomously judge the using-mode and compensate
      the heading errors. The pedestrian positioning accuracy is significantly improved
      and the walking error is only 1.4% to 2.0% of the walking distance in using-mode
      experiments of the smartphone.

PMID- 30301280
TI  - Synthesis of New Triarylpyrazole Derivatives Possessing Terminal Sulfonamide
      Moiety and Their Inhibitory Effects on PGE2 and Nitric Oxide Productions in
      Lipopolysaccharide-Induced RAW 264.7 Macrophages.
AB  - This article describes the design, synthesis, and in vitro anti-inflammatory
      screening of new triarylpyrazole derivatives. A total of 34 new compounds were
      synthesized containing a terminal arylsulfonamide moiety and a different linker
      between the sulfonamide and pyridine ring at position 4 of the pyrazole ring. All
      the target compounds were tested for both cytotoxicity and nitric oxide (NO)
      production inhibition in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages.
      Compounds 1b, 1d, 1g, 2a, and 2c showed the highest NO inhibition percentages and
      the lowest cytotoxic effect. The most potent derivatives were tested for their
      ability to inhibit prostaglandin E2 (PGE2) in LPS-induced RAW 264.7 macrophages.
      The IC50 for nitric oxide inhibition, PGE2 inhibition, and cell viability were
      determined. In addition, 1b, 1d, 1g, 2a, and 2c were tested for their inhibitory
      effect on LPS-induced inducible nitric oxide synthase (iNOS) and Cyclooxygenase 2
      (COX-2) protein expression as well as iNOS enzymatic activity.

PMID- 30301283
TI  - The modified midventral scales of Percina (Osteichthyes; Percidae).
AB  - The modified midventral scales on Percina males probably function to induce
      tactile stimulation of the female during spawning. The midbelly row of modified
      scales presumably evolved as a result of increased selective advantage of larger
      and more strongly toothed scales on the midventer; primitive and intermediate
      conditions in the evolution of the modified scales as well as a distinctly
      modified row are extant, The morphology of the scales varies seasonally and
      ontogenetically. The scales are permanent rather than deciduous as described in
      the literature interspecific variation of the modified scales is pronounced
      intersubgenerically. less so intrasubgenerically.

PMID- 30301282
TI  - Compatibility of a Silicone Impression/Adhesive System to FDM-Printed Tray
      Materials-A Laboratory Peel-off Study.
AB  - Computer-aided design (CAD) and additive manufacturing (AM) have shown promise in
      facilitating the fabrication of custom trays. Due to the clinical requirements,
      custom tray materials should achieve good bonding to the impression/adhesive
      systems. This study evaluated the retention of three fused deposition modeling
      (FDM) custom tray materials to a silicone impression/adhesive system before and
      after gritblasting (GB) by peel-off test. CAD-designed experimental test blocks
      were printed by FDM using acrylonitrile butadiene styrene (ABS), polyethylene
      terephthalate glycol copolyester (PETG), and high impact polystyrene (HIPS), and
      the reference test blocks were made of a conventional light-curing resin (n =
      11). Before and after GB, the surface topography of all tray materials was
      analysed, and the maximum strength of the test block peeled off from a silicone
      impression/adhesive system was measured. After GB, the arithmetic mean height
      (Sa) and the valley fluid retention index (Svi) of the four material groups
      declined (p < 0.05). The peel-off strength of each of the four material groups
      significantly decreased by GB (p < 0.05), but no statistical difference could be
      found among them before or after GB. In all peel-off tests, adhesive failure
      occurred at the adhesive-impression material interface. The results indicated
      ABS, HIPS, and PETG could provide sufficient adhesion to the adhesive as the
      conventional light-curing resin, and GB could reduce the roughness generated by
      FDM and weaken the bonding between the adhesive and the silicone impression.

PMID- 30301284
TI  - The structure of the ovarian ball and oogenesis in Moniliformis dubius
      (Acanthocephala).
AB  - Seven to nine days after infection of the definitive host (rat) by cystacanths,
      the genital primordium of the female acanthocephalan is transformed from a
      fragmented mass of cells into discrete ovarian balls. This is accomplished by
      envelopment of free germinal cells by somatic tissue which originates from the
      ligament sac primordium. Germinal cell nuclei then undergo repeated mitoses until
      about 21 days of development, with concurrent formation of oogonial syncytia
      which occupy the interior of the ovarian balls. Oocytes, derived from these
      oogonia, move to the periphery of the germinal syncytia for differentiation,
      growth, fertilization, shell formation, and release from the ovarian ball. After
      oogonial proliferation ceases, continued growth of the ovarian ball apparently
      results from increase in size of already present cells. Free-floating mature
      ovarian balls are found in the dorsal ligament sac; each consists of germ cells
      in various developmental stages, enveloped and pervaded by a multinucleate matrix
      syncytium of somatic origin, which functions as a follicle. Spermatozoa pass
      through the matrix cell for the internal fertilization of mature oocytes.
      Myelinated structures of an undetermined nature were found to correspond to
      previously reported polar bodies. After 100 days post-infection, the somatic
      matrix syncytium begins to manifest the degenerative effects of aging. The
      germinal tissue exhibits no subcellular signs of senescence by 154 days, but
      decreases in amount in older worms.

PMID- 30301285
TI  - The characterization of granular amoebocytes and their possible roles in the
      asexual reproduction of the polystyelid ascidian, Polyzoa vesiculiphora.
AB  - The blood cells in the bud and the zooid of the polystyelid ascidian, Polyzoa
      vesiculiphora, were examined by means of light and electron microscopy to
      identify the cells that have been named trophocytes. The large blood cells were
      abundant in the mesenchymal space of the bud, but not in that of the functional
      zooid. They contained glycogen particles, lipid droplets, large protein granules
      and autophagosomes in their cytoplasm and were identified as granular
      amoebocytes. The majority of these cells were specifically phagocytized by
      phagocytes during bud development and disappeared. These results indicate that
      the granular amoebocytes virtually represent trophocytes in Polyzoa and may
      participate in bud development via nutrient supply to the developing tissues.

PMID- 30301286
TI  - The cytology of the testaceous rhizopod Lesquereusia spiralis (Ehrenberg) Penard.
      I. Ultrastructure and shell formation.
AB  - Ultrastructure and shell formation in the testaceous ameba, Lesquereusia
      spiralis, were investigated with both scanning and transmission electron
      microscopy and X-ray microanalysis. The nucleus, surrounded by a fibrous lamina,
      contains multiple nucleoli. The cytoplasm, containing a well developed granular
      endoplasmic reticulum, also contains remnants of starch granules in stages of
      digestion. Spherical aggregates of ribosome-like particles may be seen. Golgi
      complexes seem to produce both a nonordered fibrous material and an electron
      dense vesicle. Only the latter appears to bleb off from the Golgi complex. X-ray
      microanalysis demonstration of silicon in Golgi vesicles and in some dense
      vesicles suggests that the fibrous component of the cisternae may take up and
      concentrate silica to form the electron-dense component of the vesicles. Membrane
      bound siliceous crystals are often seen adjacent to the Golgi, suggesting either
      a Golgi origin or platelet formation in vesicles after release from the Golgi
      complex. Both electron-dense bodies and siliceous platelets are released from the
      cell by a process similar to apocrine secretion and may be seen outside the cell
      in route to the shell during shell morphogenesis. Shell development involves
      fusion of electron-dense bodies to form a matrix, positioning of siliceous
      platelets in this matrix parallel to the shell surface, and development of a
      system of matrix chambers. A particulate glycoconjugate is released to the shell
      surface upon rupture of the matrix chamber.

PMID- 30301287
TI  - The neck region of the spermatozoon of Discus rotundatus (Muller) (Pulmonata,
      Stylommatophora).
AB  - The neck region of the mature spermatozoon of Discus rotundatus is described. No
      evidence for a centriole or centriolar derivative is obtained. Nine striated
      coarse fibres and the two central fibres of the axoneme extend into the base of
      the implantation fossa. The axonemal doublet system is disrupted in the neck
      region. There are two fibrous accessory structures located between the central
      doublet and the striated coarse fibres.

PMID- 30301288
TI  - Ultrastructure of the vasa deferentia of the mediterranean flour moth.
AB  - Each vas deferens of the Mediterranean flour moth, Anagasta kuehniella (Zeller),
      consists of a short swollen portion immediately below the testis, another swollen
      portion that forms a seminal vesicle, and an elongate lower portion that empties
      into one arm of the ductus ejaculatoris duplex. Three types of epithelial cells
      occur sequentially. Phagocytic cells that engulf debris from the testis form the
      anterior two-thirds of the first swollen portion. Tall secretory cells form the
      distal third of the first swollen region and extend to the seminal vesicles. The
      secretory cells surround a slit-like lumen and appear to function as a valve
      between the two swollen regions. Many membrane-enclosed secretory granules are
      stored at the apical ends of the cells and are released into the lumen together
      with small amounts of the surrounding cytoplasm. The granules remain intact while
      they are in the male tract. A second type of secretory cell forms the walls of
      the seminal vesicles and the lower vasa deferentia. These cells produce secretory
      granules whose contents become dispersed through the semen. PTA-chromic acid
      staining indicates that the seminal plasma has a high glycoprotein content. A
      thin muscle layer is basal to the epithelial cells. Both apyrene and eupyrene
      sperm undergo some development in the vasa deferentia. The epithelial cells,
      muscle, and stored sperm all undergo extensive changes with age.

PMID- 30301289
TI  - The ultrastructure of the hepatopancreatic caeca of Gammarus minus (crustacea,
      amphipoda).
AB  - The hepatopancreatic caeca of the freshwater amphipod Gummarus minus are four
      tapered blind pouches lined with a simple columnar epithelium bearing an apical
      surface of regular microvilli and resting on a basement membrane. This epithelium
      is enclosed by a tonic, striated muscularis. Each caecum consists of three
      regions. The distal zone is formed of embryonic cells having a high nuclear to
      cytoplasmic ratio and giving rise to the other cell types. The second or
      differentiation zone consists of regular tall columnar cells of two morphological
      types:(1) light staining R-cells which have a large number of lipid droplets and
      few Golgi bodies; (2) basophilic F-cells which have numerous distended Golgi
      bodies. The more proximal secretory zone forms the majority of each diverticulum.
      This mature zone is formed from R-cells and large, basophilic, vacuolated B-cells
      which differentiate from F-cells. The secretory cell sequence appears to be E
      cell - F-cell - B-cell with secretion being apocrine in nature. The exact
      relationship of Rcells to the other cell types is questionable, but the R-, F -
      and B-cells all appear to be able to absorb and store nutrients. Within the
      Malacostraca the hepatopancreatic epithelium of Amphipoda more closely
      approximates that of Decapoda than that of the Isopoda.

PMID- 30301290
TI  - Cytochemical observations of larval development in Eunapius fragilis (Leidy):
      Porifera; spongillidae.
AB  - Freshwater sponges of the family Spongillidae reproduce sexually through
      formation of a parenchymula larva. The cytochemical characteristics of
      parenchymula larval metamorphosis - beginning with the blastula and terminating
      with the motile escape stage - for the spongillid Eunapius fragilis (Leidy) have
      been defined using both absorption and fluorescent cytochemical methods,
      particularly those demonstrating protein end-groups. Morphogenesis of the
      parenchymula larva of E. fragilis involves the interrelated processes of
      cytodifferentiation and mobilization of reserve materials. Larval development has
      been categorized into five stages, from blastula (stage I) through the escape
      stage (stage V). Parenchymula development is characterized by morphogenetic
      precocity, a fact influencing the rate of mobilization of cytoplasmic reserves,
      cytodifferentiation, and the fate of individual cell types. With attainment of
      the stage V parenchymula, the larva is, essentially, a mobile adult sponge
      exhibiting flagellated chambers, canal systems, a well defined connective tissue
      stroma, a diverse cell population consisting of specialized elements and a
      totipotent archeocyte reserve, and a terminal epitheliocyte line. The present
      study recognizes differences in development within the spongillids as well as
      within more remote poriferan taxa - emphasizing the need for detiled
      understanding of particular processes in individual species before proposing
      major generalizations about development in this ancient but evolutionally
      specialized group.

PMID- 30301291
TI  - Dynamics and acoustical radiation of Porichthys notatus' swim bladder system.
AB  - The swimbladder system of the plainfin midshipman consists of a gas-filled
      bladder and two intrinsic sonic muscles which are attached to the bladder at
      opposite sides. An experimental and analytical study was conducted to define the
      physical characteristics of this dynamic system, and to relate these
      characteristics to radiated acoustical pressure pulses. Results indicate that the
      system has two degrees of freedom, being comprised of two inertial, stiffness and
      damping components; the first and second mode components of a 23.1-centimeter
      midshipman are 0.002 and 0.019 kg (inertial) 2130 and 106,000 newtons per meter
      (stiffness) and 0.25 and 0.10 (damping) respectively. This system is excited by
      the sonic muscle forcing function which equals
      ?documentclass{article}?pagestyle{empty}?begin{document}$ 0.00236{?rm}?sin
      ?frac{{2?pi {?rm t}}}{{0.0045{?rm}?sec}}{?rm newtons}. $?end{document} Two system
      frequency response peaks were observed; the first was 110 hertz, at the flat
      section next to the sonic muscle, and was very near the repetition frequency of
      the sonic muscle pulses; the second was 350 hertz, at the hemispherical section,
      which was the frequency of the acoustical pressure pulse. These phenomena
      describe a dynamical system closely "tuned" to its forcing function, and a system
      which is highly responsive to acoustical pressure pulses radiated by neighboring
      midshipmen. The acoustical pressure pulse coincides in wave form with the
      hemispherical bladder wall acceleration.

PMID- 30301292
TI  - Fine structure of an elongated dorso-ventrally compressed echinoderm
      (holothuroidea) spermatozoon.
AB  - The spermatozoon of Cucumaria pseudocurata is unique among those of the
      echinoderms in that it is tabloid in shape, i.e., elongated and dorsoventrally
      compressed. The sperm consists of a dorsal surface which contains an extensive
      striated rootlet-like structure located within a dorsal groove and a ventral
      surface which contains a medially situated acrosome. A single mitochondrion lies
      at the base of the nucleus. The flagellum is unusual in that a 9 + 3 tubular
      arrangement is observed in the mid-tail region. The acrosome consists of an
      acrosomal granule bounded by a limiting membrane and a surrounding periacrosomal
      layer. The granule is irregular in shape with the anterior-posterior surfaces
      flaring out, forming pockets in the periacrosomal material. The ventral granule
      surface bulges forming a close association with the plasma membrane. The dorsal
      surface is indented. Ventral to the depression (within the granule) is a small
      area containing a particulate-fibrous material. To the inside of the granule
      limiting membrane there is a second membrane-like structure (incomplete) which
      extends from the anterior-posterior surfaces around the dorsal face of the
      granule. Dorso-medial to the granule the periacrosomal layer contains a
      particulate-fibrous region lodged within the granule depression. This material is
      presumably the precursor of the acrosomal filament. Prominent cytoplasmic folds
      extend off from the basal flagellar region. The proximal and distal centrioles
      are situated perpendicular to one another within the mitochondrion. Centriolar
      satellite materials are associated with both centrioles. Toward the base of the
      tail the satellite of the distal centriole consists of nine radiating arms
      extending at an angle of 45 degrees  to the axis of the centriole. Each arm
      terminates in a dense thickening. The striated rootlet extends anteriorly from
      the distal centriole to just below the level of the acrosome.

PMID- 30301293
TI  - External morphology of antennae and their sense organs in the roach
      Gromphadorhina brunneri (Blattoidea: Dictyoptera).
AB  - The antennae and their sense organs in nymphs and adult roaches of Gromphadorhina
      brunneri, were investigated and described. The number of segments and sensillae
      of the nymphal antennae depend on the developmental stage. Sexual dimorphism is
      pronounced. Males have longer antennae than females as well as an abundance of
      especially long sensory hairs (long wavy hairs), which are probably responsible
      for the perception of female sex pheromones. They also have more thin-walled
      sensory hairs, for instance, sensilla trichodea. On a morphological basis the
      sensillae of Gromphadorhina brunneri, were named and classified. Long wavy hairs
      and large sensory hairs appear to be present also in a related species, G.
      portentosa, but are lacking in others. Their distribution on the antennae varies
      greatly from that in G. portentosa but their structure varies only slightly.
      These two types of sense organs are considered to be specialized forms of
      sensilla chaetica. They are contact chemoreceptors, as are two other types of
      sensilla chaetica. Furthermore, thin-walled chemoreceptors are present, such as
      sensilla trichodea, sensilla basiconica, sensilla coeloconica and a typical
      mechanoreceptor, the sensillum campaniformium.

PMID- 30301294
TI  - An ultrastructural study of byssus stem formation in Mytilus californianus.
AB  - In Mytilus californianus, root lamellae of the byssus stem are formed by two
      morphologically distinct exocrine cell types. Type 1 cells contain large
      ellipsoid granules which are ultrastructurally identical to those of the collagen
      gland associated with byssus thread formation: these granules are secreted only
      at the base of the stem generator. Type 2 cells contain small cylindroid granules
      which are secreted only from the lateral surfaces of generator septa. The
      resultant matrix is biphasic because the two secretions are incompletely mixed.
      Lamellar sheets of matrix are propelled outward by the action of cilia and are
      molded into a cylinder at the neck region of the stem. However, the stem retains
      a lamellar pattern. Byssus threads are attached to the stem by flattened rings
      formed from thread material which is secreted into the cervical crevice
      surrounding the neck. The microanatomy of the stem forming region is described
      and a new term, "stem generator," is proposed for this organ.

PMID- 30301295
TI  - A reconsideration of the phylogeny of the tetrapod heart.
AB  - After dissecting a variety of vertebrate hearts and extensively reviewing the
      literature, I have drawn some conclusions concerning the phylogeny of the
      tetrapod heart that differ from commonly expressed viewpoints in the literature.
      It is probable that the absence of an interventricular septum in amphibians is a
      primitive feature (rather than representing a loss). The complete
      interventricular septum of crocodilians and birds probably evolved primarily from
      the major horizontal septum of the typical (noncrocodilian) reptilian heart, with
      a smaller part representing a new development. The interventricular septum of
      mammals probably also evolved primarily from the reptilian horizontal septum.
      There is no reason to assume that the mammalian heart and aortic arches evolved
      directly from a pre-reptilian stage, as is often assumed. The evidence upon which
      these conclusions are based is given.

PMID- 30301296
TI  - A comparative study of the chemical defensive system of tenebrionid beetles III.
      Morphology of the glands.
AB  - The morphology of the abdominal defensive glands and associated structures of 115
      species of tenebrionid beetles was studied on KOH cleared material. The glands
      and reservoirs of all Tenebrionidae are homologous and evolved as a pair of sacs
      from the intersegmental membrane between sternites VII and VIII. On the basis of
      reservoir morphology and secretory cell tubule termination, seven provisional
      gland types were established. Several of the types include species from several
      tribes, and several tribes contain several gland types, indicating possible
      incongruencies between the taxonomy and phylogeny of the family. Morphological
      trends in the evolution of the glands include: increase of reservoir capacity,
      constriction of the proximal portion of the sacs into distinct exit ducts,
      release of secretion by exuding or spraying rather than everting, and
      concentration of the secretory cell tubule terminations into restricted fields,
      collecting ducts or ampullae. The morphology of the glands of 58 species is
      illustrated and the results are discussed in light of the current taxonomy of the
      Tenebrionidae.

PMID- 30301297
TI  - A study of the fine structure of the accessory muscle of the horseshoe crab,
      Tachypleus gigas.
AB  - The accessory muscle of the walking leg of the horseshoe crab, Tachypleus gigas,
      was examined electron microscopically. The muscle fibers vary in size but are
      small in diameter, when compared with other arthropod skeletal muscles. They are
      striated with A, I, Z and poorly defined H bands. The sarcomere length ranges
      from 3-10 MUm with most sarcomeres in the range of about 6 MUm. The myofilaments
      are arranged in lamellae in larger fibers and less well organized in the smaller
      ones. Each thick filament is surrounded by 9-12 thin filaments which overlap. The
      SR is sparse but well organized to form a fenestrated collar around the fibrils.
      Individual SR tubules are also seen among the myofibrils. Long transverse tubules
      extend inward from the sarcolemma to form dyads or triads with the SR at the A-I
      junction. Both dyads and triads coexist in a single muscle fiber, a feature
      believed to have evolutionary significance. The neuromuscular relationship is
      unique. In the region of synaptic contact, the sarcolemma is usually elevated to
      form a large club-shaped structure containing no myofilaments and few other
      organelles. The axons or axon terminals and glial elements penetrate deep into
      the club-shaped sarcoplasm and form synapses with the fiber. As many as 13
      terminals have been observed within a single section. Synaptic vesicles of two
      types are found in the axon terminals.

PMID- 30301298
TI  - Chelonian mental glands.
AB  - A survey of 69 of the 74 currently recognized chelonian genera revealed that 21
      genera in three families (Emydidae, Platysternidae and Testudinidae) possess
      paired integumentary glands or gland vestiges in the anterior throat skin. These
      glands are here termed mental glands; they are holocrine and may be classified
      morphologically as follows: Class I mental glands are large, complex, multilobed,
      have specialized ducts, and are found only in the genus Gopherus: Class II mental
      glands are small, simple sacklike invaginations containing secretory cells or
      keratinizing cells. The structure of Class II glands varies from distinctive and
      saccular to shallow keratinized invaginations having no glandular tissue; they
      are found only in the families Platysternidae and Emydidae. Mental glands occur
      in 17 of the 22 genera in the subfamily Batagurinae (sensu McDowell, 64); only 2
      of 9 genera in the subfamily Emydinae have these glands. The taxonomic occurrence
      of mental glands suggests that they are primitive structures. The loss of mental
      glands in most emydines is interpreted as a subfamilial trend toward
      integumentary simplification.

PMID- 30301299
TI  - A simplified placenta-like system for the transport of extraembryonic nutrients
      during embryogenesis of Bugula neritina (bryozoa).
AB  - Embryos of the marine cheilo-ctenostome bryozoan Bugula neritina undergo a marked
      increase in volume (about 500-fold) during embryogenesis while being retained in
      a brood chamber. Previous morphological studies indicate that shortly after
      transfer of the zygote to the brood chamber, the epithelium of the maternally
      derived portion of the brood chamber, the ooecial vesicle, differentiates in
      regions adjacent to the embryonary space from a squamous to a columnar form
      suggesting that the parent is involved as a source of extraembryonic nutrients
      required for the extensive growth of the embryo. Results of the present
      ultrastructural study indicate that hypertrophy of the epithelial cells occurs
      only in that region of the ooecial vesicle which opposes the embryo, that
      differentiation (and subsequent regression) of the lining are predictable events
      correlated with the onset (and termination) of embryonic growth, and that
      hypertrophied cells are well equipped for the synthesis and transport of
      macromolecular materials across the vesicle wall to the developing embryo.
      Further, that portion of the embryo's ectoderm (the presumptive metasomal sac) in
      contact with this hypertrophied epithelium is morphologically specialized for the
      uptake of nutrients. Finally, shortly before release of the larva, this intimate
      association of the metasomal sac tissue and the hypertrophied ooecial vesicle
      lining epithelium is terminated by invagination of the sac and atrophy of the
      lining.

PMID- 30301300
TI  - The Relationship between Plasma Oxytocin Levels and Social Anxiety Symptoms.
AB  - OBJECTIVE: The pathophysiology of social anxiety disorder (SAD) is not yet well
      understood, but previous research has suggested that oxytocin is associated with
      social behavior and may play a role in human anxiety states and anxiety-related
      traits. The aim of this study was to investigate the possible relationship
      between social anxiety symptoms and plasma oxytocin levels. METHODS: Twenty-three
      male patients with SAD and 28 healthy male controls participated in this study.
      All participants were assessed using the Mini International Neuropsychiatric
      Interview (MINI) and the Liebowitz Social Anxiety Scale (LSAS). Multivariate
      regression analysis was performed to identify associations between plasma
      oxytocin levels and SAD. RESULTS: In multiple regression models, after
      controlling for age and years of education, we found that higher oxytocin levels
      were significantly associated with higher total LSAS scores (R2 =0.157,
      coefficient=0.145, 95% CI=-0.0005-0.291, p=0.051) and fear subscale scores (R2
      =0.134, coefficient=0.083, 95% CI=0.007-0.159, p=0.034) in the SAD group.
      CONCLUSION: In this study, increased plasma oxytocin levels were associated with
      higher social anxiety symptoms among SAD patients, but not among controls. This
      might be because among SAD patients, higher oxytocin (OT) secretion is an
      insufficient compensatory attempt to reduce social anxiety symptoms.

PMID- 30301301
TI  - Use of a Machine Learning Algorithm to Predict Individuals with Suicide Ideation
      in the General Population.
AB  - OBJECTIVE: In this study, we aimed to develop a model predicting individuals with
      suicide ideation within a general population using a machine learning algorithm.
      METHODS: Among 35,116 individuals aged over 19 years from the Korea National
      Health & Nutrition Examination Survey, we selected 11,628 individuals via random
      down-sampling. This included 5,814 suicide ideators and the same number of non
      suicide ideators. We randomly assigned the subjects to a training set (n=10,466)
      and a test set (n=1,162). In the training set, a random forest model was trained
      with 15 features selected with recursive feature elimination via 10-fold cross
      validation. Subsequently, the fitted model was used to predict suicide ideators
      in the test set and among the total of 35,116 subjects. All analyses were
      conducted in R. RESULTS: The prediction model achieved a good performance [area
      under receiver operating characteristic curve (AUC)=0.85] in the test set and
      predicted suicide ideators among the total samples with an accuracy of 0.821,
      sensitivity of 0.836, and specificity of 0.807. CONCLUSION: This study shows the
      possibility that a machine learning approach can enable screening for suicide
      risk in the general population. Further work is warranted to increase the
      accuracy of prediction.

PMID- 30301302
TI  - Effects of 5HT1A Activation on Depression Profile Following 5-HT Depletion in
      Rats Lacking Social Attachment Since Weanling.
AB  - OBJECTIVE: Post weanling isolation-reared (IR) rats are featured with depressive
      phenotype, yet its mechanism is not clearly defined particularly in terms of the
      involvement of central 5-HT1A receptors. The present study aims to examine the
      effects of 5HT1A activation on forced swim test (FST) in IR rats following 5-HT
      depletion. METHODS: Social control (SOC) and IR rats received an
      intracerebraoventricular (ICV) injection of 5-HT depletion agent, 5,7-DHT. 14
      days after the surgery, rats were assessed their performance in FST with or
      without the challenge with a 5-HT1A agonist, 8-OH-DPAT. Rats were then sacrificed
      for analyzing their 5-HT tissue levels and the expressions of their 5-HA1A
      receptors in prefrontal cortex (PFC), hippocampus (HPX), and amygdala (AMY).
      RESULTS: 5,7-DHT decreased the tissue concentration of 5-HT in both IR and SOC
      rats. IR rats were more immobile and less sensitive to the lesion-induced
      immobility, however this effect was reversed by acute challenge of 8-OH-DPAT. 5,7
      DHT lesion increased the expression of PFC 5-HT1A receptors. CONCLUSION: The
      integrity of central 5-HT system is developmentally crucial for the 5-HT1A
      relevant depression profile in rats of social isolation.

PMID- 30301303
TI  - A Novel Bio-Psychosocial-Behavioral Treatment Model of Panic Disorder.
AB  - To conceptualize a novel bio-psychosocial-behavioral treatment model of panic
      disorder (PD), it is necessary to completely integrate behavioral,
      psychophysiological, neurobiological, and genetic data. Molecular genetic
      research on PD is specifically focused on neurotransmitters, including serotonin,
      neuropeptides, glucocorticoids, and neurotrophins. Although pharmacological
      interventions for PD are currently available, the need for more effective, faster
      acting, and more tolerable pharmacological interventions is unmet. Thus,
      glutamatergic receptor modulators, orexin receptor antagonists, corticotrophin
      releasing factor 1 receptor antagonists, and other novel mechanism-based anti
      panic therapeutics have been proposed. Research on the neural correlates of PD is
      focused on the dysfunctional "cross-talk" between emotional drive (limbic
      structure) and cognitive inhibition (prefrontal cortex) and the fear circuit,
      which includes the amygdala-hippocampus-prefrontal axis. The neural perspective
      regarding PD supports the idea that cognitive-behavioral therapy normalizes
      alterations in top-down cognitive processing, including increased threat
      expectancy and attention to threat. Consistent with the concept of "personalized
      medicine," it is speculated that Research Domain Criteria can enlighten further
      treatments targeting dysfunctions underlying PD more precisely and provide us
      with better definitions of moderators used to identify subgroups according to
      different responses to treatment. Structuring of the "negative valence systems"
      domain, which includes fear/anxiety, is required to define PD. Therefore,
      targeting glutamate- and orexin-related molecular mechanisms associated with the
      fear circuit, which includes the amygdala-hippocampus-prefrontal cortex axis, is
      required to define a novel bio-psychosocial-behavioral treatment model of PD.

PMID- 30301304
TI  - Smart Stress Care: Usability, Feasibility and Preliminary Efficacy of Fully
      Automated Stress Management Application for Employees.
AB  - OBJECTIVE: We developed a fully automated smartphone-based stress management
      application and explored its usability, potential feasibility, and preliminary
      efficacy for stress management in Korean employees. METHODS: Healthy employees
      working in large public enterprises were enrolled. Participants used our
      automated stress management application for four weeks. With the application,
      they monitored their stress level and life style factors. Personalized stress
      management techniques, including psychoeducation and cognitive behavioral
      technique, were also provided based on their stress level and lifestyle pattern.
      In 2014, additional relaxation techniques were incorporated. Participants' mental
      health status and lifestyle pattern were self-assessed at baseline and at 4 weeks
      after using the application. RESULTS: A total of 68 subjects were recruited. The
      application generally received high satisfaction rating. After the intervention,
      perceived stress level was significantly decreased, both in 2013 and 2014 (BEPSI
      K score pre. vs. post. 14.27 vs. 11.00, F=12.49, p=0.001 in 2013; 12.05 vs.
      10.00, F=17.18, p<0.001). In 2014, depression symptom severity was also
      significantly decreased (CES-D score pre- vs. Post-, 17.66 vs. 11.95, F=9.76,
      p=0.004). The effects were more significant in females and in those <35 years.
      CONCLUSION: Our fully automated stress management application is acceptable and
      usable, showing preliminary efficacy for reducing employees' stress levels.

PMID- 30301305
TI  - How Game Addiction Rates and Related Psychosocial Risk Factors Change Within 2
      Years: A Follow-Up Study.
AB  - OBJECTIVE: Prospective data of risky online gamers in Turkey is missing.
      Therefore, we aimed to investigate the change in gaming behaviors and addiction
      rates of Travian players within two years to search diagnostic stability of
      internet gaming disorder and some psychosocial risk factors. METHODS: 110
      responders completed the whole questionnaire package including 21-item Game
      Addiction Scale (GAS), Satisfaction with Life Scale (SLS), Rosenberg Self-Esteem
      Scale (RSES), and Multi-dimensional Scale of Perceived Social Support (MSPSS). A
      hierarchical linear modeling approach was followed to test the linear change in
      game addiction scores of the participants from 2013 to 2015. RESULTS: GAS scores
      of gamers significantly decreased within two years (p=0.026). MSPSS scores
      significantly and negatively associated with GAS scores (p<0.001) and the
      negative association of time remained significant (p=0.035). Decrement in the
      MSPSS scores in two years was associated with increment in GAS scores. 9 (90%) of
      10 participants with internet gaming disorder according to monothetic format and
      26 (52%) of 50 participants with internet gaming disorder according to polythetic
      format were found to not to meet the diagnosis in the follow-up. 33 out of all
      participants reported that they were not playing any online games for at least
      last 6 months. CONCLUSION: Social support seems to be a protective factor for
      game addiction and diagnosis of internet gaming disorder has low temporal
      stability among Travian players in Turkey.

PMID- 30301306
TI  - Reliability and Validity of the Korean Version of Health Anxiety Questionnaire.
AB  - OBJECTIVE: Health anxiety can be defined by concern about health in the absence
      of a pathology. The Health Anxiety Questionnaire (HAQ) based on the cognitive
      behavioral model can be useful for evaluating the severity and the structure of
      health anxiety. This study aims to verify the reliability and validity of Korean
      version of HAQ (K-HAQ). METHODS: For reliability, test-retest reliability and
      internal consistency were analyzed. For construct validity, exploratory factor
      analysis (EFA) and confirmatory factor analysis (CFA) were conducted. Receiver
      Operating Characteristic (ROC) analysis was performed to identify the optimal cut
      off score. RESULTS: Cronbach's alpha was 0.92, and r value of test-retest
      reliability was 0.84. In the EFA, 4- and 5-factor model showed cumulative
      percentile of variance of 60% or more. In the CFA, the 4-factor model was found
      to be the most appropriate and simplest (chi2 =397.33, df=187, CFI=0.909,
      TLI=0.888, RMSEA=0.077). In the ROC analysis, the cut-off score was 20 points.
      CONCLUSION: It is expected that K-HAQ can be helpful to evaluate the severity of
      health anxiety and make therapeutic plans because KHAQ can help explore the
      cognitive, emotional, and behavioral structure of health anxiety by each factor.

PMID- 30301307
TI  - Does Psychodrama Affect Perceived Stress, Anxiety-Depression Scores and Saliva
      Cortisol in Patients with Depression?
AB  - OBJECTIVE: Little is known about the effects of psychodrama group therapy on the
      level of stress, anxiety and depression of the group members, and the biological
      markers of stress. The aim of this study test cortisol level as a biological
      reflection of some mental characteristics gained by the psychodrama method in
      coping with stress. METHODS: Depressive patients aged between 18 and 65 years,
      who diagnosed with depression according to DSM-5, without psychiatric
      comorbidity, who do not use drugs and were available for psychodrama were
      enrolled into the study. These patients were evaluated using the Perceived Stress
      Scale, State-Trait Anxiety Inventory and Beck Depression Inventory. In order to
      observe the circadian rhythm of cortisol, samples were collected from the
      participants before lunch, before dinner and before going to sleep on the day
      before psychodrama and on the 0, 15th, and 30th minutes after awakening in the
      morning of the psychodrama day; as well as just before and after the psychodrama
      session. Saliva cortisol level just before the initial session of psychodrama
      group therapy was compared with the saliva cortisol level just after the last
      psychodrama session at the end of 16 weeks. RESULTS: Statistically significant
      difference was determined between the scores of perceived stress scale, STAI-1,
      STAI-2, beck depression inventory and salivary cortisol level before and after
      psychodrama session. There was significant decrease in both the scale scores and
      salivary cortisol after vs. before psychodrama. CONCLUSION: This results is
      important as it shows the biological aspect of clinical improvement. Further
      studies would provide us with better understanding of the effects of psychodrama
      group psychotherapy on depressive mood and biological projections by means of
      short-term and long-term follow-up studies.

PMID- 30301308
TI  - Mediating Effect of Internet Addiction on the Association between Resilience and
      Depression among Korean University Students: A Structural Equation Modeling
      Approach.
AB  - OBJECTIVE: This study examined the mediating role of internet addiction in the
      association between psychological resilience and depressive symptoms. METHODS:
      837 Korean university students completed a survey with items of demographic
      information, Connor-Davidson Resilience Scale (CD-RISC), Internet Addiction Test
      (IAT), and Patient Health Questionnaire (PHQ-9) in 2015. The complex associations
      among psychological resilience, internet addiction, and depressive symptoms were
      delineated using structural equation models. RESULTS: In the most parsimonious
      model, the total effect and indirect effect of resilience on depressive symptoms
      via internet addiction, were statistically significant. The goodness of fit of
      the measurement model was satisfactory with fit indices, normed fit index (NFI)
      of 0.990, non-normed fit index (NNFI) of 0.997, comparative fit index (CFI) of
      0.998, root mean square error (RMSEA) of 0.018 (90%CI=0.001-0.034); and Akaike
      Information Criterion (AIC) of -21.049. CONCLUSION: The association between
      psychological resilience and depressive symptoms was mediated by internet
      addiction in Korean university students. Enhancement of resilience programs could
      help prevent internet addiction and reduce the related depression risks.

PMID- 30301309
TI  - Spatial Learning and Memory Using a Radial Arm Maze with a Head-Mounted Display.
AB  - OBJECTIVE: A radial arm maze (RAM) is an essential tool for assessing spatial
      learning and memory. Although this tool is widely used to study deficits in
      spatial memory in animal models, it has several restrictions that prevent its
      adaptation to human research and training. Therefore, we developed a head-mounted
      display RAM (HMD-RAM) program for humans and verified its validity by comparing
      it to the results obtained by previous RAM studies. We also compared the HMD and
      a flat monitor as experimental devices. METHODS: Forty participants were
      recruited for the current study (Study 1: 20 participants with the HMD device;
      Study 2: 20 participants with the flat monitor). They navigated a virtual room as
      a first-person viewer and used environmental landmarks to remember their spatial
      position and orientation. The main dependent measures were working memory error,
      reference memory error, detection time, travel distance, and participant's head
      movements. To validate the program, participants also conducted
      neuropsychological assessments and self-reported measures. RESULTS: The results
      for HMD-RAM tasks were consistent with the results of previous research conducted
      on animals, and the HMD elicited a higher sense of presence, immersion, and
      simulator sickness than the flat monitor. According to post-experiment questions
      on navigation strategy, creating landmarks was important when people were
      discovering locations in their environment, and an HMD was beneficial for better
      navigation strategy. CONCLUSION: These results suggest that the HMD-RAM is
      valuable for estimating spatial learning and memory in humans and may be a useful
      tool for early diagnosis of deficits in spatial learning and memory, including
      amnestic mild cognitive impairment and Alzheimer's disease.

PMID- 30301310
TI  - Comparison of three risk stratification models for non-clear cell renal cell
      carcinoma patients treated with temsirolimus as first-line therapy.
AB  - Background/Aims: For metastatic renal cell carcinoma (RCC), various prognostic
      scoring systems have been developed. However, owing to the low prevalence of
      nonclear cell RCC, the three most commonly used tools were mainly developed based
      on patients with clear cell histology. Accordingly, this study applied three
      prognostic models to Korean non-clear cell RCC patients treated with first-line
      temsirolimus. Methods: This study analyzed data for 74 patients with non-clear
      cell RCC who were treated with temsirolimus as the first-line therapy at eight
      medical centers between 2011 and 2016. The receiver-operating characteristic
      (ROC) curves for the different prognostic models were analyzed. Results: Twenty
      seven (36.5%), 24 (32.4%), and 44 patients (59.5%) were assigned to the poor
      prognosis groups of the Memorial Sloan-Kettering Cancer Center (MSKCC),
      International Metastatic RCC Database Consortium (IMDC), and Advanced Renal Cell
      Carcinoma (ARCC) risk stratification models, respectively. All three prognostic
      models reliably discriminated the risk groups to predict progression-free
      survival and overall survival (p < 0.001). The area under the ROC curve (AUC) for
      progression and survival was highest for the ARCC model (0.777; 0.734), followed
      by the IMDC (0.756; 0.724) and the MSKCC (0.742; 0.712) models. Furthermore, the
      sensitivity and specificity for predicting progression were highest with the ARCC
      model (sensitivity 63.6%, specificity 85.7%), followed by the MSKCC (sensitivity
      58.2%, specificity 86.5%) and the IMDC models (sensitivity 56.4%, specificity
      85.7%). Conclusions: All three prognostic models accurately predicted the
      survival of the non-clear cell RCC patients treated with temsirolimus as the
      first-line therapy. Furthermore, the ARCC risk model performed better than the
      other risk models in predicting survival.

PMID- 30301311
TI  - Evaluating the Headspace Volatolome, Primary Metabolites, and Aroma
      Characteristics of Koji Fermented with Bacillus amyloliquefaciens and Aspergillus
      oryzae.
AB  - Production of good Koji primarily depends upon the selection of substrate
      materials and fermentative microflora, which together influence the
      characteristic flavor and aroma. Herein, we performed comparative metabolomic
      analyses of volatile organic compounds (VOCs) and primary metabolites for Koji
      samples fermented individually with Bacillus amyloliquefaciens and Aspergillus
      oryzae. The VOCs and primary metabolites were analyzed using headspace solid
      phase microextraction (HS-SPME) followed by gas chromatography time-of-flight
      mass spectrometry (GC-TOF-MS). In particular, alcohols, ketones, and furans were
      mainly detected in Bacillus-fermented Koji (Bacillus Koji, BK), potentially due
      to the increased levels of lipid oxidation. A cheesy and rancid flavor was
      characteristic of Bacillus Koji, which is attributable to high content of typical
      'off-flavor' compounds. Furthermore, the umami taste engendered by 2
      methoxyphenol, (E,E)-2,4-decadienal, and glutamic acid was primarily detected in
      Bacillus Koji. Alternatively, malty flavor compounds (2-methylpropanal, 2
      methylbutanal, 3-methylbutanal) and sweet flavor compounds (monosaccharides and
      maltol) were relatively abundant in Aspergillus-fermented Koji (Aspergillus Koji,
      AK). Hence, we argue that the VOC profile of Koji is largely determined by the
      rational choice of inocula, which modifies the primary metabolomes in Koji
      substrates, potentially shaping its volatolome as well as the aroma
      characteristics.

PMID- 30301312
TI  - Analysis of the Microbiota on Lettuce (Lactuca sativa L.) Cultivated in South
      Korea to Identify Foodborne Pathogens.
AB  - Lettuce (Lactuca sativa L.) is a major ingredient used in many food recipes in
      South Korea. Lettuce samples were collected during their maximum production
      period between April and July in order to investigate the microbiota of lettuce
      during different seasons. 16S rRNA gene-based sequencing was conducted using
      Illumina MiSeq, and real-time PCR was performed for quantification. The number of
      total bacterial was greater in lettuce collected in July than in that collected
      in April, albeit with reduced diversity. The bacterial compositions varied
      according to the site and season of sample collection. Potential pathogenic
      species such as Bacillus spp., Enterococcus casseliflavus, Klebsiella pneumoniae,
      and Pseudomonas aeruginosa showed season-specific differences. Results of the
      network co-occurrence analysis with core genera correlations showed
      characteristics of bacterial species in lettuce, and provided clues regarding the
      role of different microbes, including potential pathogens, in this microbiota.
      Although further studies are needed to determine the specific effects of regional
      and seasonal characteristics on the lettuce microbiota, our results imply that
      the 16S rRNA gene-based sequencing approach can be used to detect pathogenic
      bacteria in lettuce.

PMID- 30301314
TI  - A Novel Approach for Sericin-Conjugated Silver Nanoparticle Synthesis and Their
      Potential as Microbicide Candidates.
AB  - Silver nanoparticles have been widely applied for biomedical areas owing to their
      potent antiviral and antibacterial activities. Synthesis of silver nanoparticles
      using biomacromolecules is more efficient, environment-friendly, and cost-saving
      compared with the traditional approach. In this paper, a novel approach was
      developed to establish a reaction system with Ag+-BH4--sericin to synthesize
      silver nanoparticles conjugated to sericin (AgNPs-Sericin). Sericin could be as a
      good dispersant and stabilizing agent, which is able to modify nanoscaled AgNPs,
      the average diameter of which was only 3.78 +/- 1.14nm prepared in a 0.3 mg/ml
      sericin solution. The characterizations of the AgNPs-Sericin were determined by
      FTIR, thermogravimetry, and XRD analyses. The results showed that the synthesized
      AgNPs conjugated with sericin as organic phase. Via SAED and XRD analysis, we
      showed that these AgNPs formed polycrystalline powder with a face-centered cubic
      structure of bulk metals. Moreover, we investigated the antiviral and
      antibacterial activities of AgNPs-Sericin, and the results showed that AgNPs
      Sericin exhibited potent anti-HIV-1 activity against CCR5-tropic and CXCR4-tropic
      strains, but no significant cytotoxicity was found toward human genital
      epithelial cells compared with free silver ions, which are accepted as a commonly
      used potent antimicrobial agent. Moreover, its antibacterial activity was
      determined via flow cytometry. The results showed that AgNPs-Sericin could
      suppress gram-negative (E. coli) and gram-positive (S. aureus) bacteria, but more
      was potent for the gram-negative one. We concluded that our AgNPs-Sericin could
      be a potential candidate as a microbicide or antimicrobial agent to prevent
      sexually transmitted infections.

PMID- 30301313
TI  - Anti-Angiogenesis Effects Induced by Octaminomycins A and B against HUVECs.
AB  - In the course of studies to discover natural products with anti-angiogenic
      properties, two cyclic octapeptides, octaminomycins A (1) and B (2), were
      isolated from the cultures of Streptomyces sp. RK85-270. Octaminomycins
      suppressed the vascular endothelial growth factor (VEGF)-induced proliferation,
      adhesion, tube formation, migration, and invasion of HUVECs. Anti-angiogenic
      activity was futher confirmed in vivo by the chicken chorioallantoic membrane
      assay. We also identified that 1 and 2 inhibited the phosphorylation of VEGF
      receptor 2, AKT, and ERK1/2 and the expression and activities of MMP-2 and MMP-9.
      These results suggest that 1 and 2 may serve as potential scaffolds for the
      development of therapeutic agents to angiogenesis-dependent diseases.

PMID- 30301315
TI  - Generation and Characterization of a Neutralizing Human Monoclonal Antibody to
      Hepatitis B Virus PreS1 from a Phage-Displayed Human Synthetic Fab Library.
AB  - The hepatitis B virus (HBV) envelope contains small (S), middle (M), and large
      (L) proteins. PreS1 of the L protein contains a receptor-binding motif crucial
      for HBV infection. This motif is highly conserved among 10 HBV genotypes (A-J),
      making it a potential target for the prevention of HBV infection. In this study,
      we successfully generated a neutralizing human monoclonal antibody (mAb), 1A8
      (IgG1), that recognizes the receptor-binding motif of preS1 using a phage
      displayed human synthetic Fab library. Analysis of the antigen-binding activity
      of 1A8 for different genotypes indicated that it can specifically bind to the
      preS1 of major HBV genotypes (A-D). Based on Bio-Layer interferometry, the
      affinity (KD) of 1A8 for the preS1 of genotype C was 3.55 nM. 1A8
      immunoprecipitated the hepatitis B virions of genotypes C and D. In an in vitro
      neutralization assay using HepG2 cells overexpressing the cellular receptor
      sodium taurocholate cotransporting polypeptide, 1A8 effectively neutralized HBV
      infection with genotype D. Taken together, the results suggest that 1A8 may
      neutralize the four HBV genotypes. Considering that genotypes A-D are most
      prevalent, 1A8 may be a neutralizing human mAb with promising potential in the
      prevention and treatment of HBV infection.

PMID- 30301316
TI  - Regulation of AKT Activity by Inhibition of the Pleckstrin Homology Domain
      PtdIns(3,4,5)P3 Interaction Using Flavonoids.
AB  - The serine-threonine kinase AKT plays a pivotal role in tumor progression and is
      frequently overactivated in cancer cells; this protein is therefore a critical
      therapeutic target for cancer intervention. We aimed to identify small molecule
      inhibitors of the pleckstrin homology (PH) domain of AKT to disrupt binding of
      phosphatidylinositol-3,4,5-trisphosphate (PIP3), thereby downregulating AKT
      activity. Liposome pulldown assays coupled with fluorescence spectrometry were
      used to screen flavonoids for inhibition of the AKT PH-PIP3 interaction. Western
      blotting was used to determine the effects of the inhibitors on AKT activation in
      cancer cells, and in silico docking was used for structural analysis and
      optimization of inhibitor structure. Several flavonoids showing up to 50%
      inhibition of the AKT PH-PIP3 interaction decreased the level of AKT activation
      at the cellular level. In addition, the modified flavonoid showed increased
      inhibitory effects and the approach would be applied to develop anticancer drug
      candidates. In this study, we provide a rationale for targeting the lipid-binding
      domain of AKT, rather than the catalytic kinase domain, in anticancer drug
      development.

PMID- 30301317
TI  - Trends in medical disputes involving anesthesia in the period July 2009-June
      2018: an analysis of the Korean Society of Anesthesiologists database.
AB  - Background: To identify trends in injuries and substandard care associated with
      anesthesia, we analyzed the Korean Society of Anesthesiologists database, which
      includes anesthesia-related case files from July 2009 to June 2018. Methods: Case
      characteristics, injuries, and outcomes were compared between the first part
      (July 2009-June 2014, n = 105) and the second part (July 2014-June 2018, n = 92)
      of the analyzed time period. Results: Overall, 132 cases resulted in death. The
      proportion of fatal cases for sedation was similar to that for general anesthesia
      (66.2% vs. 76.3%). The proportion of cases with permanent injury or death
      decreased significantly in the second part of the period compared with the first
      part (76.1% vs. 93.3%, P = 0.002). With a growing trend in the proportion of
      sedation cases, a similar number of sedation and general anesthesia cases were
      referred during the overall period (77 and 76 cases, respectively). Propofol
      based regimens remained the dominant sedation method (89.7% in the first part vs.
      78.9% in the second part). A respiratory origin was identified as the most common
      adverse event in cases of permanent injury or death (98/182, 53.8%).
      Specifically, eight and five cases with permanent injury Sor death were related
      to local anesthetic systemic toxicity (LAST) and beach-chair positioning for
      shoulder surgery, respectively. Conclusions: Despite the decreasing trend in
      injury severity, several characteristic injury profiles were identified: lack of
      vigilance in propofol-based sedation, neurological injuries related to the beach
      chair position, and LAST occurring during tumescent anesthesia or brachial plexus
      block.

PMID- 30301318
TI  - The quest for patient safety.

PMID- 30301319
TI  - Training in Bariatric and Metabolic Endoscopic Therapies.
AB  - Bariatric endoscopy is an emerging subspecialty for gastroenterologists
      encompassing a broad array of procedures including primary endoscopic bariatric
      and metabolic therapies and the treatment of complications of bariatric surgery.
      In addition, comprehensive understanding of lifestyle intervention and
      pharmacotherapy are essential to successful outcomes. This review summarizes
      goals and steps of training for this emerging field.

PMID- 30301320
TI  - New findings and trends for depth of anesthesia monitoring.

PMID- 30301321
TI  - Successful use of spinal anesthesia for an urgent cesarean section in a
      parturient with a severe Klippel-Trenaunay syndrome.

PMID- 30301322
TI  - Characterization of phage-resistant strains derived from Pseudomonas tolaasii
      6264, which causes brown blotch disease.
AB  - Pseudomonas tolaasii 6264 is a representative strain that causes bacterial blotch
      disease on the cultivated oyster mushroom, Pleurotus ostreatus. Bacteriophages
      are able to sterilize the pathogenic P. tolaasii strains and therefore, they can
      be applied to make a disease-free cultivation farm, known as "phage therapy". For
      successful phage therapy, the characterization of phage-resistant strains is
      necessary, since they are frequently induced from the original pathogenic
      bacteria in the presence of phages. When 10 phages were incubated with P.
      tolaasii 6264, their corresponding phage-resistant strains were obtained. In this
      study, changes in pathogenic, genetic, and biochemical characteristics as well as
      the acquired phage resistance of these strains were investigated. In the
      phylogenetic analyses, all phage-resistant strains were identical to the original
      parent strain based on the sequence comparison of 16S rRNA genes. When various
      phage-resistant strains were examined by three different methods, pitting test,
      white line test, and hemolytic activity, they were divided into three groups:
      strains showing all positive results in three tests, two positive in the first
      two tests, and all negative. Nevertheless, all phage-resistant strains showed
      that their pathogenic activities were reduced or completely loss.

PMID- 30301323
TI  - Heterologous expression and characterization of a laccase from Laccaria bicolor
      in Pichia pastoris and Arabidopsis thaliana.
AB  - Laccases can oxidize a variety of phenolic and non-phenolic substrates including
      synthetic dyes. In this research, a laccase gene Lcc9 from Laccaria bicolor was
      chemically synthesized and optimized to heterogeneous expression in Pichia
      pastoris and Arabidopsis thaliana. The properties of recombinant laccase
      expressed by P. pastoris were investigated. The laccase activity was optimal at
      3.6 pH and 40  degrees C. It exhibited Km and Vmax values of 0.565 mmol l-1 and
      1.51 MUmol l-1 min-1 for ABTS respectively. As compared with untransformed
      control plants, the laccase activity in crude extracts of transgenic lines
      exhibited a 5.4 to 12.4-fold increased. Both laccases expressed in transgenic P.
      pastoris or A. thaliana could decolorize crystal violet. These results indicated
      that L. bicolor laccase gene may be transgenically exploited in fungi or plants
      for dye decolorization.

PMID- 30301324
TI  - Design, optimization and verification of 16S rRNA oligonucleotide probes of
      Fluorescence in-situ hybridization for targeting Clostridium spp. and Clostridium
      kluyveri.
AB  - Fluorescence in-situ hybridization (FISH) is a common and popular method to
      investigate microbial communities in natural and engineered environments. In this
      study, two specific 16S rRNA-targeted oligonucleotide probes CLZ and KCLZ were
      designed and verified to quantify the genus Clostridium and the species
      Clostridium kluyveri. The optimal concentration of hybridization buffer solution
      for both probes CLZ and KCLZ was 30% (w/v). The specificity of the designed
      probes was high by using pellets from the pure reference strains. Feasibility was
      tested using the samples of Luzhou-flavor liquor manufacturing cellar. The
      effectiveness of detecting target cells appears to vary widely in different
      environments. In pit mud, the detection effectiveness of the target cell by probe
      CLZ and KCLZ was 49.11% and 32.14%, respectively. The quantitative analysis by
      FISH technique of microbes in pit mud and fermented grains showed consistency
      with the results detected by qPCR and PCR-DGGE techniques, which showed that the
      probes CLZ and KCLZ were suitable to analyze the biomass of Clostridium spp. and
      C. kluyveri during liquor fermentation. Therefore, this study provides a method
      for quantitative analysis of Clostridium spp. and C. kluyveri and monitoring
      their community dynamics in microecosystems.

PMID- 30301325
TI  - Application and Analysis of Rhizopus oryzae Mycelia Extending Characteristic in
      Solid-state Fermentation for Producing Glucoamylase.
AB  - Enhanced application of solid-state fermentation (SSF) in industrial production
      and the influence of SSF of Rhizopus K1 on glucoamylase productivity were
      analyzed using flat band method. A growth model was implemented through SSF of
      Rhizopus K1 in this experiment, and spectrophotometric method was used to
      determine glucoamylase activity. Results showed that in bran and potato culture
      medium with 70% moisture in a loose state, MU of mycelium reached to 0.15 h-1
      after 45 h of culture in a thermostatic water bath incubator at 30  degrees C.
      Under a low-magnification microscope, mycelial cells appeared uniform, bulky with
      numerous branches, and not easily ruptured. The generated glucoamylase activity
      reached to 55 U/g (dry basis). This study had good utilization value for
      glucoamylase production by Rhizopus in SSF.

PMID- 30301326
TI  - Isolation and Characterization of Bifidobacterium longum subsp. longum BCBR-583
      for Probiotic Applications in Fermented Foods.
AB  - Recent human gut microbiome studies have supported that the genus Bifidobacterium
      is one of the most beneficial bacteria for human intestinal health. To develop a
      new probiotic strain for functional food applications, fourteen fecal samples
      were collected from healthy Koreans and a strain BCBR-583 was newly selected and
      isolated from a 25-year-old Korean woman's fecal sample using the selective
      medium for Bifidobacterium. Subsequent fructose-6-phosphate phosphoketolase
      (F6PPK) test and 16S rRNA gene sequencing analysis of the strain BCBR-583
      confirmed that it belongs to B. longum subsp. longum. The stress resistance tests
      showed that it has oxygen and heat tolerance activities (5- and 3.9-fold increase
      for 24 h at 60 and 120 rpm, respectively; 78.61 +/- 6.67% survival rate at 45
      degrees C for 24 h). In addition, gut environment adaptation tests revealed that
      this strain may be well-adapted in the gut habitat, with gastric acid/bile salt
      resistance (85.79 +/- 1.53%, survival rate under 6 h treatments of gastric acid
      and bile salt) and mucin adhesion (73.72 +/- 7.36%). Furthermore, additional
      tests including cholesterol lowering assay showed that it can reduce 86.31 +/-
      1.85% of cholesterol. Based on these results, B. longum BCBR-583 has various
      stress resistance for survival during food processing and environmental
      adaptation activities for dominant survival in the gut, suggesting that it could
      be a good candidate for fermented food applications as a new probiotic strain.

PMID- 30301328
TI  - Magnified single-balloon enteroscopy in the diagnosis of intestinal follicular
      lymphoma: a case series.
AB  - The objective of this study was to evaluate the magnified endoscopic findings in
      the diagnosis of follicular lymphoma in the small intestine in comparison with
      those of intestinal follicular lymphoma and lymphangiectasia. Four patients with
      follicular lymphoma and 3 with lymphangiectasia in the small intestine were
      retrospectively analyzed. A prototype magnifying singleballoon enteroscope was
      used. The findings of the intestinal follicular lymphoma and lymphangiectasia
      were retrospectively analyzed to determine the magnified endoscopic findings of
      follicular lymphoma in the small intestine. Opaque white granules were observed
      in 3 of the 4 patients with follicular lymphoma. Magnified narrow-band imaging
      (NBI) of the opaque white granules showed stretched microvessels, which had a
      diminutive tree-like appearance. The remaining patient had no opaque white
      granules and only displayed whitish villi. Magnified NBI observation of the
      whitish villi revealed the absence of marginal villus epithelium, which was
      confirmed by histology. The magnified NBI enteroscopy revealed the diminutive
      tree-like appearance on the opaque white granules and the absence of marginal
      villus epithelium of the whitish villi in intestinal follicular lymphoma. These
      findings may be useful in diagnosing follicular lymphoma.

PMID- 30301327
TI  - Rates of metachronous adenoma after curative resection for left-sided or right
      sided colon cancer.
AB  - Background/Aims: We determined the rates of metachronous colorectal neoplasm in
      colorectal cancer (CRC) patients after resection for right (R)-sided or left (L)
      sided cancer. Methods: Consecutive CRC patients who had undergone surgical
      resection for curative intent in our hospital between 2001 and 2004 were
      identified. R-sided colonic cancers refer to cancer proximal to splenic flexure
      whereas L-sided cancers include rectal cancers. Patients were included only if
      they had a clearing colonoscopy performed either before or within 6 months after
      the operation. Findings of surveillance colonoscopy performed up to 5 years after
      colonic resection were included in the analysis. Results: Eight hundred and sixty
      three CRC patients underwent curative surgical resection during the study period.
      Three hundred and twenty-seven patients (107 R-sided and 220 L-sided) fulfilled
      the inclusion criteria and had at least 1 postoperative surveillance colonoscopy
      performed. The proportion of patients who had polyp and adenoma on surveillance
      colonoscopy was significantly higher among patients with L-sided than R-sided
      cancers (polyps: 30.9% vs. 19.6%, P=0.03; adenomas: 25.5% vs. 13.1%, P=0.01). The
      mean number of adenoma per patient on surveillance colonoscopy was also higher
      for patients with L-sided than R-sided tumors (0.52; 95% confidence interval
      [CI], 0.37-0.68 vs. 0.22; 95% CI, 0.08-0.35; P<0.01). Multivariate analysis
      showed that L-sided cancers, age, male gender and longer follow-up were
      independent predictors of adenoma detection on surveillance colonoscopy.
      Conclusions: Patients with Lsided cancer had a higher rate of metachronous polyps
      and adenoma than those with R-sided cancer on surveillance colonoscopy.

PMID- 30301329
TI  - Seven days triple therapy for eradication of Helicobacter pylori does not alter
      the disease activity of patients with inflammatory bowel disease.
AB  - Background/Aims: The influences of Helicobacter pylori eradication therapy on the
      disease course of inflammatory bowel disease (IBD) are still unclear. We
      therefore conducted a multicenter, retrospective cohort study to evaluate the
      safety of H. pylori eradication therapy for IBD patients. Methods: IBD patients
      with H. pylori eradication from 2005 to 2015 (eradication group) and control
      patients (non-eradication group; 2 paired IBD patients without H. pylori
      eradication matched with each eradicated patient) were included. IBD exacerbation
      (increased/additional IBD drug or IBD-associated hospitalization/surgery) and
      disease improvement based on the physicians' global assessment were investigated
      at baseline, and at 2 and 6 months after eradication or observation. Results: A
      total of 429 IBD (378 ulcerative colitis, 51 Crohn's disease) patients,
      comprising 144 patients in the eradication group and 285 patients in the non
      eradication group, were enrolled at 25 institutions. IBD exacerbation was
      comparable between groups (eradication group: 8.3% at 2 months [odds ratio, 1.76;
      95% confidence interval, 0.78-3.92; P=0.170], 11.8% at 6 months [odds ratio,
      1.60; 95% confidence interval, 0.81-3.11; P=0.172]). Based on the physicians'
      global assessment at 2 months, none of the patients in the eradication group
      improved, whereas 3.2% of the patients in the non-eradication group improved
      (P=0.019). Multivariate analysis revealed that active disease at baseline, but
      not H. pylori eradication, was an independent factor for IBD exacerbation during
      2 months' observation period. The overall eradication rate was 84.0%-comparable
      to previous reports in non-IBD patients. Conclusions: H. pylori eradication
      therapy does not alter the short-term disease activity of IBD.

PMID- 30301330
TI  - Response to hepatitis B vaccination in patients with inflammatory bowel disease:
      a prospective observational study in Korea.
AB  - Background/Aims: Testing for hepatitis B virus (HBV) serologic markers and
      appropriate vaccination are required in the management of inflammatory bowel
      disease (IBD) patients. We evaluated immunogenicity for HBV in IBD patients and
      the response to the HBV vaccination. Methods: From May 2014 to August 2016,
      patients diagnosed with IBD were prospectively included and evaluated for anti
      HBs antibody, anti-HBc antibody, and HBs antigen. Among the 73 patients who were
      confirmed with nonimmunity to HBV, 44 patients who had completed the 3-dose HBV
      vaccination series received a single booster vaccination, while 29 patients who
      had not completed the vaccinations series or were unsure of receiving the
      vaccination received a full vaccination series. Results: An optimal response was
      obtained in 70.5% of the patients in the booster group, and 89.7% of the patients
      in the full vaccination group. Age younger than 26 years (odds ratio [OR], 6.01;
      95% confidence interval [CI], 1.15-31.32; P=0.033) and a complete previous
      vaccination series (OR, 0.15; 95% CI, 0.03-0.80; P=0.026) were associated with
      optimal vaccine response. Previous complete vaccination series (OR, 0.11; 95% CI,
      0.02-0.73; P=0.022) was the only predictive factor for lower compliance.
      Conclusions: The response to the HBV vaccination was lower in patients older than
      26 years and for those patients with a complete vaccination history. Since
      patients with a complete vaccination history also had poor compliance, serum HBV
      titers should be checked more thoroughly, and a full vaccination series should be
      administered in cases when there is a negative response to the booster
      vaccination.

PMID- 30301331
TI  - High risk of tuberculosis during infliximab therapy despite tuberculosis
      screening in inflammatory bowel disease patients in India.
AB  - Background/Aims: The data on the risk of tuberculosis (TB) reactivation with
      infliximab (IFX) in patients with inflammatory bowel disease (IBD) from TB
      endemic countries, like India, is limited. The risk of TB reactivation on IFX and
      its predictors in patients with IBD was assessed. Methods: This retrospective
      review included consecutive patients with IBD who received IFX, and were on
      follow-up from January 2005 to November 2017. The data was recorded on
      age/disease duration, indications for IFX, screening for latent tuberculosis
      (LTB) before IFX, response to IFX, incidence and duration when TB developed after
      IFX, and type of TB (pulmonary [PTB]/extra-pulmonary [EPTB]/disseminated).
      Results: Of 69 patients (22 ulcerative colitis/47 Crohn's disease; mean age,
      35.6+/-14.5 years; 50.7% males; median follow-up duration after IFX, 19 months
      [interquartile range, 5.5-48.7 months]), primary non-response at 8 weeks and
      secondary loss of response at 26 and 52 weeks were seen in 14.5%, 6% and 15%
      patients respectively. Prior to IFX, all patients were screened for LTB, 8
      (11.6%) developed active TB (disseminated, 62.5%; EPTB, 25%; PTB, 12.5%) after a
      median of 19 weeks (interquartile range, 14.0-84.5 weeks) of IFX. Of these 8
      patients' none had LTB, even when 7 of 8 were additionally screened with contrast
      enhanced chest tomography. Though not statistically significant, more patients
      with Crohn's disease than ulcerative colitis (14.9% vs. 4.5%, P=0.21), and those
      with past history of TB (25% vs. 9.8%, P=0.21), developed TB. Age, gender,
      disease duration, or extraintestinal manifestations could not predict TB
      reactivation. Conclusions: There is an extremely high rate of TB with IFX in
      Indian patients with IBD. Current screening techniques are ineffective and it is
      difficult to predict TB after IFX.

PMID- 30301332
TI  - Patient self-reported symptoms using visual analog scales are useful to estimate
      endoscopic activity in ulcerative colitis.
AB  - Background/Aims: In clinical practice, colonoscopy has been regarded as the gold
      standard for the evaluation of disease severity as well as mucosal healing in
      ulcerative colitis (UC). Some activity indices incorporating patient symptoms as
      parameters have been shown to reflect the endoscopic activity of UC. The aim of
      this study was to examine whether self-reported symptoms with visual analog
      scales (VAS) can predict endoscopic activity. Methods: A cross-sectional study of
      150 UC patients who underwent colonoscopy with submission of VAS scores of 4
      symptoms: general condition, bloody stools, stool form, and abdominal pain (0: no
      symptoms, 10: the most severe symptoms). Each VAS score was compared with
      colonoscopic activity assessed with the Mayo endoscopic subscore (MES). Results:
      All VAS scores were significantly correlated with the endoscopic severity
      (Spearman correlation coefficients of general condition, bloody stools, stool
      form, and abdominal pain: 0.63, 0.64, 0.58, and 0.43, respectively). Mucosal
      healing defined as MES 0 alone was predicted by VAS score <1.5 on general
      condition or 0 on bloody stools with sensitivity of 0.84 and 0.76 and specificity
      of 0.66 and 0.76, respectively. Additionally, VAS score <2.5 on stool form
      predicted active lesions in distal colorectum alone with sensitivity of 0.67 and
      specificity of 0.66, suggesting that this item could predict the indication of
      topical therapy. Conclusions: Self-reported VAS scores on symptoms were
      correlated with endoscopic activity of UC. To clarify the relationship between
      VAS and mucosal healing, further validation studies are needed.

PMID- 30301333
TI  - Medication non-adherence in inflammatory bowel diseases is associated with
      disability.
AB  - Background/Aims: Medication non-adherence is common in inflammatory bowel
      diseases (IBD). The short-term consequences of non-adherence include increased
      disease relapse but the long-term impact upon patients in terms of daily
      functional impairment are less well characterized. Identifying negative outcomes,
      such as disability, may encourage adherence. Methods: Consecutive ambulatory IBD
      subjects completed the Medication Adherence Rating Scale (MARS; non-adherence
      defined as <=16), Inflammatory Bowel Diseases Disability Index (IBD-DI;
      disability: <3.5) and Beliefs about Medicines Questionnaire (high
      necessity/concerns: >=16). The primary outcome was the association between
      medication non-adherence and disability. Secondary outcomes were the predictors
      of these outcomes. Results: A total of 173 subjects on IBD maintenance
      medications were recruited (98 Crohn's disease, 75 ulcerative colitis: median IBD
      DI, -5.0; interquartile range [IQR], -14.0 to 4.0 and median MARS, 19.0; IQR, 18
      to 20) of whom 24% were non-adherent. Disability correlated significantly with
      medication non-adherence (r=0.38, P<0.0001). Median IBD-DI for non-adherers was
      significantly lower than adherers (-16.0 vs. -2.0, P<0.0001). Predictors of
      disability included female sex (P=0.002), previous hospitalization (P=0.023),
      management in a referral hospital clinic (P=0.008) and medication concerns
      (P<0.0001). Non-adherence was independently associated with difficulty managing
      bowel movements (odds ratio [OR], 3.71; 95% confidence interval [CI], 1.50-9.16,
      P=0.005), rectal bleeding (OR, 2.69; 95% CI, 1.14-6.36; P=0.024) and
      arthralgia/arthritis (OR, 2.56; 95% CI, 1.11-5.92; P=0.028). Conclusions:
      Medication non-adherence was associated with significantly increased disability
      in IBD. Female gender, higher disease severity and medication concerns were
      additional predictors of disability.

PMID- 30301334
TI  - 5-Aminosalicylic acid aggravates colitis mimicking exacerbation of ulcerative
      colitis.
AB  - Ulcerative colitis (UC) is one of the major clinical phenotypes of inflammatory
      bowel diseases. Although 5-aminosalicylic acid (5-ASA) is widely used for UC and
      its efficacy and safety have been demonstrated, a few patients paradoxically
      develop a severe exacerbation of colitis by 5-ASA administration. It is crucial
      to know clinical features including endoscopic findings in this condition for
      making a correct diagnosis and a prompt decision to withdraw the medication.
      Here, we report case series with UC exacerbated by 5-ASA. Medical records of 8 UC
      patients experiencing an exacerbation of colitis after induction of 5-ASA that
      was improved by the withdrawal of 5-ASA but also re-aggravated by dose increase
      or re-administration of 5-ASA were reviewed. The patients were newly diagnosed
      with UC, started 5-ASA and developed an exacerbation in approximately 2 to 3
      weeks. They did not appear to have systemic allergic reactions. Seven of the 8
      patients had a high fever. Three of 5 patients who undertook total colonoscopy
      showed right-side-dominant colitis. These findings suggest clinical
      characteristics in this condition. Further assessment of clinical and endoscopic
      features in more cases is necessary for establishing diagnostic criteria and
      understanding underlying mechanisms in those cases where 5-ASA aggravates the
      colitis.

PMID- 30301335
TI  - Usefulness of fecal immunochemical test and fecal calprotectin for detection of
      active ulcerative colitis.
AB  - Background/Aims: Ulcerative colitis undergoes periods of exacerbation and
      remission. Fecal calprotectin levels increase with gut inflammation and correlate
      with endoscopic disease activity in ulcerative colitis. Intestinal blood loss and
      fecal immunochemical test levels also correlate with endoscopic disease activity.
      This study statistically evaluated the usefulness of fecal calprotectin, fecal
      immunochemical test, and C-reactive protein (CRP) as markers of disease activity.
      Methods: A total 106 ulcerative colitis patients who underwent endoscopy and
      fecal calprotectin, fecal immunochemical test, and CRP testing, from March 2015
      to August 2016, were retrospectively reviewed. Disease activity was assessed
      using a partial Mayo score and Mayo endoscopic score. The ability of fecal and
      serologic tests to reflect endoscopic disease severity was statistically
      evaluated. Results: Among 106 patients, 68 underwent endoscopy and stool study
      within 2 weeks. In patients with mild to severe activity, fecal immunochemical
      test and fecal calprotectin were superior to CRP at Mayo endoscopic score
      detection rate. The area under the curves of fecal immunochemical test and fecal
      calprotectin for the detection of Mayo endoscopic score >=1 were 0.956 and 0.942,
      respectively, and were superior to that of CRP (0.756). At Mayo endoscopic score,
      the effects of combination of fecal immunochemical test and CRP or fecal
      calprotectin and CRP were found to be higher than those of the independent fecal
      immunochemical test or fecal calprotectin. Conclusions: Fecal immunochemical test
      and fecal calprotectin can effectively detect active ulcerative colitis better
      than remission. As these markers reflect the status of mucosal inflammation, they
      may reduce the requirement for invasive endoscopic examination.

PMID- 30301336
TI  - Probe-based confocal laser endomicroscopy in the differential diagnosis of
      inflammatory bowel diseases: a case series.

PMID- 30301338
TI  - Vitamin D deficiency is associated with disease activity in patients with Crohn's
      disease.
AB  - Background/Aims: Previous data suggest that vitamin D has a significant role in
      inflammatory bowel disease (IBD). We investigated the incidence of vitamin D
      deficiency in Korean patients with IBD and the correlation between serum vitamin
      D level and disease activity. Methods: We retrospectively analyzed the medical
      records of patients with IBD whose serum vitamin D levels were checked.
      Deficiency of 25-hydroxyvitamin D was defined as <20 ng/mL. Disease activity was
      evaluated using the partial Mayo score for ulcerative colitis (>=2 defined as
      active disease) and Harvey-Bradshaw index for Crohn's disease (>=4 defined as
      active disease). Results: We enrolled 87 patients with IBD (UC, 45; CD, 42).
      Among them, 65.5% (57/87) were men, with a mean age of 44.9+/-15.1 years (range,
      18-75 years). The mean duration of disease was 4.7+/-4.8 years (range, 0.1-17.1
      years). Vitamin D deficiency was found in 73.6% (64/87) of patients with IBD.
      Patients with IBD (mean vitamin D level, 16.3+/-9.0 ng/mL) showed lower vitamin D
      level than the healthy control group (mean vitamin D level, 20.4+/-7.0 ng/mL),
      with no statistically significant difference (P=0.136). Disease activity was
      inversely correlated with vitamin D deficiency in patients with CD (P=0.007).
      However, no correlation was observed in patients with UC (P=0.134). Conclusions:
      Approximately 75% of Korean patients with IBD showed vitamin D deficiency state.
      Vitamin D deficiency is associated with disease activity, particularly in
      patients with CD.

PMID- 30301339
TI  - Experience of patients with inflammatory bowel disease in using a home fecal
      calprotectin test as an objective reported outcome for self-monitoring.
AB  - Background/Aims: Fecal calprotectin (fC) level is a predictive marker of mucosal
      healing for patients with inflammatory bowel disease (IBD). Home fC tests are now
      available. We evaluated the performance of the smartphone-based IBDoc home
      testing system in patients with IBD and obtained their feedback as an objective
      patient-reported outcome. Methods: This prospective study enrolled consecutive
      patients with IBD in clinical remission. fC in the same stool sample was assessed
      by using both the laboratory test (Quantum Blue calprotectin test) and home test
      (IBDoc). The correlation between the 2 tests was analyzed using the Pearson
      method. In addition, the patients were asked to fill a questionnaire based on
      their experience. Results: Fifty-one patients with IBD (68 tests and 49
      questionnaires) were included. The correlation between Quantum Blue test and
      IBDoc was good (r=0.776, P<0.0001). After the test, 56% patients found IBDoc easy
      to perform, and 96% were satisfied with it. Thirty-nine patients (80%) had a
      strong (>70%) probability to use it for future monitoring if the price was
      acceptable. By using 250 MUg/g as the cutoff, the agreement between home test and
      laboratory results was 80%, and by using 600 MUg/g as the cutoff, the agreement
      increased to 92%. Conclusions: The correlation between the laboratory and home
      tests was good. Most patients found the home test to be feasible and easy to use
      and preferred it over laboratory test and endoscopy for monitoring. Therefore,
      the home test could be used as an objective patient-reported outcome.

PMID- 30301340
TI  - The current capacity and quality of colonoscopy in Korea.
AB  - Background/Aims: Little is known for the capacity and quality of colonoscopy, and
      adherence to colonoscopy surveillance guidelines in Korea. This study aimed to
      investigate the present and potential colonoscopic capacity, colonoscopic
      quality, and adherence to colonoscopy surveillance guidelines in Korea. Methods:
      We surveyed representative endoscopists of 72 endoscopy units from June to August
      2015, using a 36-item questionnaire regarding colonoscopic capacity, quality, and
      adherence to colonoscopy surveillance guidelines of each hospitals. Results:
      Among the 62 respondents who answered the questionnaire, 51 respondents were
      analyzed after exclusion of 11 incomplete answers. Only 1 of 3 of endoscopy units
      can afford to perform additional colonoscopies in addition to current practice,
      and the potential maximum number of colonoscopies per week was only 42. The
      quality of colonoscopy was variable as reporting of quality indicators of
      colonoscopy were considerably variable (29.4%-94.1%) between endoscopy units.
      Furthermore, there are substantial gaps in the adherence to colonoscopy
      surveillance guidelines, as concordance rate for guideline recommendation was
      less than 50% in most scenarios. Conclusions: The potential capacity and quality
      of colonoscopy in Korea was suboptimal. Considering suboptimal reporting of
      colonoscopic quality indicators and low adherence rate for colonoscopy
      surveillance guidelines, quality improvement of colonoscopy should be underlined
      in Korea.

PMID- 30301337
TI  - Usefulness of fecal calprotectin by monoclonal antibody testing in adult Japanese
      with inflammatory bowel diseases: a prospective multicenter study.
AB  - Background/Aims: Noninvasive objective monitoring is advantageous for optimizing
      treatment strategies in patients inflammatory bowel disease (IBD). Fecal
      calprotectin (FCP) is superior to traditional biomarkers in terms of assessing
      the activity in patients with IBD. However, there are the differences among
      several FCP assays in the dynamics of FCP. In this prospective multicenter trial,
      we investigated the usefulness of fecal FCP measurements in adult Japanese
      patients with IBD by reliable enzyme immunoassay using a monoclonal antibody.
      Methods: We assessed the relationship between FCP levels and disease or
      endoscopic activity in patients with ulcerative colitis (UC, n=64) or Crohn's
      disease (CD, n=46) compared with healthy controls (HCs, n=64). Results: FCP
      levels in UC patients strongly correlated with the Disease Activity Index
      (rs=0.676, P<0.0001) and Mayo endoscopic subscore (MES; rs=0.677, P<0.0001). FCP
      levels were significantly higher even in patients with inactive UC or CD compared
      with HCs (P=0.0068, P<0.0001). The optimal cutoff value between MES 1 and 2
      exhibited higher sensitivity (94.1%). FCP levels were significantly higher in
      active UC patients than in inactive patients (P<0.001), except those with
      proctitis. The Crohn's Disease Activity Index tended to correlate with the FCP
      level (rs=0.283, P=0.0565). Conclusions: Our testing method using a monoclonal
      antibody for FCP was well-validated and differentiated IBD patients from HCs. FCP
      may be a useful biomarker for objective assessment of disease activity in adult
      Japanese IBD patients, especially those with UC.

PMID- 30301341
TI  - IBD2020 global forum: results of an international patient survey on quality of
      care.
AB  - Background/Aims: IBD2020 is a global forum for standards of care in inflammatory
      bowel disease (IBD). The aim of the IBD2020 survey was to identify and describe
      variations in quality care of IBD. Methods: Patients with IBD from Finland,
      Italy, France, Canada, Germany, UK, Spain and Sweden were surveyed during 2013 to
      2014, covering: disease characteristics; impact on life and work; organization
      and perceived quality of care. Results: Seven thousand five hundred and seven
      patients participated (median age, 39 years [range, 10-103 years]; 2,354 male
      [31.4%]), including 4,097 (54.6%) with Crohn's disease (CD) and 3,410 (45.4%)
      with ulcerative colitis (UC). Median time from symptom onset to diagnosis was 1
      year for both CD (range, 0-47 years) and UC (range, 0-46 years), with no clear
      evidence of improvement in diagnostic delay over the preceding 24 years. Half of
      the patients (3,429; 50.0%) rated their care as "excellent" or "very good," with
      similar results for CD and UC across countries. Five factors were significantly
      (P<0.01) associated with perceived good quality of care: quality of specialist
      communication; review consultation being long enough; failure to share
      information; no access to a dietician; speed of advice. Conclusions: The IBD2020
      survey has highlighted areas related to quality of care of IBD from the patients'
      perspective, with scope for improvement.

PMID- 30301342
TI  - Clinicopathological feature and treatment outcome of patients with colorectal
      laterally spreading tumors treated by endoscopic submucosal dissection.
AB  - Background/Aims: Endoscopic submucosal dissection (ESD) is an advanced technique
      that can be used to treat precancerous and early colorectal neoplasms by
      facilitating en bloc resection regardless of tumor size. In our study, we
      investigated the clinicopathological feature and the treatment outcome of
      patients with colorectal laterally spreading tumors (LSTs) that were treated by
      ESD. Methods: The study enrolled all of 210 patients with colorectal LSTs who
      underwent ESD. Clinical outcomes were analyzed by retrospectively reviewing
      medical records. Results: A cancerous pit pattern (Vi/Vn) was more common in
      pseudo-depressed (PD) subtype than in flat elevated (FE) subtype. The incidence
      of adenocarcinoma in the PD subtype and nodular mixed (NM) subtypes was
      significantly higher than in the homogenous (HG) subtype and FE subtype. The en
      bloc and R0 resection rates were 89.0% and 85.7%, respectively. The bleeding and
      perforation rates were 5.2% and 1.9%, respectively. The mean procedure time was
      much longer in the PD subtype than in the FE subtype. The en bloc resection rate
      was significantly higher in the NM subtype than in the HG subtype. However, there
      were no statistically significant differences in mean procedure time, en bloc
      resection rate, R0 resection rate, bleeding rate, or perforation rate between LST
      granular and LST-nongranular types. Conclusions: These results indicate that ESD
      is acceptable for treating colorectal LSTs concerning en bloc resection, curative
      resection, and risk of complications. Careful consideration is required for
      complete resection of the PD subtype and NM subtype because of their higher
      malignant potential.

PMID- 30301343
TI  - Development and diversity of lactic acid producing bacteria and bifidobacteria in
      healthy full term Indian infants from Himachal Pradesh.
AB  - Background/Aims: The initial microbial colonization is a crucial step for the
      healthy development of an infant. Previous studies from India reported the
      dominance of target microbial species among Indian infants without any analysis
      on the diversity of target groups. This is the first study from India with an
      objective to investigate the establishment and diversity of lactic acid producing
      bacteria (LAB) and bifidobacteria in vaginally delivered, full term, breastfed
      infants for the first 4 months after birth. Methods: Present study used
      polymerase chain reaction-denaturating gradient gel electrophoresis (PCR-DGGE)
      based sequence analysis of LAB and bifidobacteria in healthy infants. The results
      were used to compare the development and early colonization by LAB and
      bifidobacteria using diversity indices during the initial months of development
      of gut microbiota in infants. Results: During the first 4 months, the Shannon
      diversity index (H) of LAB increased from 1.16 to 1.318 and for bifidobacteria
      the H increased from 0.975 to 1.293 (P<0.05). Higher Sorenson's pair wise
      similarity coefficient was observed for LAB and bifidobacteria during 2nd and the
      3rd month. The species of the genera Enterococcus, Streptococcus, and
      Lactobacillus were dominant among the LAB group whereas Bifidobacterium breve was
      dominant species among Bifidobacterium group. Conclusions: Our results indicate
      that in breast fed infants, the microbial diversity of LAB and bifidobacteria
      increased during the period of study.

PMID- 30301344
TI  - Clinical features and outcomes in spontaneous intramural small bowel hematoma:
      Cohort study and literature review.
AB  - Background/Aims: Spontaneous intramural small bowel hematoma (SISBH) is an
      extremely rare complication of anticoagulant or antiplatelet therapy. We assessed
      the clinical characteristics and outcomes of patients with SISBH according to the
      anatomical location of the hematoma. Methods: From January 2003 to February 2016,
      medical records for all patients hospitalized for SISBH at 2 tertiary referral
      hospitals were retrospectively reviewed. The primary outcome was requirement for
      surgery. Results: A total of 37 patients were enrolled. The mean age was 74.1
      years. Among them, 33 patients (89.2%) were taking anticoagulant and/or
      antiplatelet agents. Duodenal intramural hematoma was detected in 4 patients
      (10.8%), jejunal in 16 (43.2%), and ileal in 17 (45.9%). Compared to jejunal and
      ileal involvement, duodenal intramural hematoma was significantly associated with
      high Charlson comorbidity index and low levels of white blood cells, hemoglobin,
      and platelets in the blood. SISBH in the duodenum was related to thrombocytopenia
      in 3 patients following systemic chemotherapy for malignancy. All patients with
      SISBH showed clinical improvement with conservative therapy. Mean length of
      hospital stay was 9.35 days. Independent predictors of a hospital stay of more
      than 7 days were body weight less than 60 kg (odds ratio [OR], 12.213; 95%
      confidence interval [CI], 1.755-84.998; P=0.011) and a history of cerebrovascular
      accidents (OR, 6.667; 95% CI, 1.121-39.650; P=0.037). Conclusions: Compared to
      jejunal and ileal involvement, thrombocytopenia may result in spontaneous
      duodenal intramural hematoma among patients who are treated with systemic
      chemotherapy for malignancies. Patients with SISBH have excellent clinical
      outcomes with conservative therapy regardless of the anatomical location of the
      hematoma.

PMID- 30301345
TI  - Methoxyphosphinidene and Isomeric Methylphosphinidene Oxide.
AB  - A rare oxyphosphinidene (Me-OP) has been generated in the triplet ground state
      through either photolysis (266 nm) or flash-vacuum pyrolysis (FVP, 700  degrees
      C) of methoxydiazidophosphine MeOP(N3)2. Upon ArF laser irradiation (193 nm), an
      unprecedented isomerization from Me-OP to the long-sought methylphosphinidene
      oxide (Me-PO) occurs in cryogenic Ne- and N2-matrices. Alternatively, the latter
      can be efficiently generated through photolysis (193 nm) or FVP (ca. 700  degrees
      C) of methylphosphoryl diazide MeP(O)(N3)2, in which the elusive nitrene
      intermediate MeP(O)(N3)N in the triplet ground state has been also observed by IR
      (with 15N-labeling) and EPR (| D/ hc| = 1.545 cm-1 and | E/ hc| = 0.003 95 cm-1)
      spectroscopy.

PMID- 30301346
TI  - Synthesis of Phenolic Glycosides: Glycosylation of Sugar Lactols with Aryl
      Bromides via Dual Photoredox/Ni Catalysis.
AB  - Multifarious sugar lactols were efficiently transformed into the corresponding
      phenolic glycosides by treating with aryl bromides in acetonitrile with
      Ir[dF(CF3)ppy]2(dtbbpy)(PF6) as a photocatalyst under visible light irradiation.
      Both pyranoses and furanoses or even disaccharide could all suffer this
      glycosylation protocol under mild reaction conditions. A variety of phenyl
      glycosides can be produced in moderate to good yields (up to 93% yield), and a
      gram scale process of this protocol was also well-established.

PMID- 30301347
TI  - Admicellar Polymerization Coating of CNF Enhances Integration in Degradable
      Nanocomposites.
AB  - A water-based one-pot synthesis strategy for converting cellulose nanofibrils
      (CNF) into a hydrophobic and processable biopolymer grade is devised. CNF was
      chemically modified through admicellar polymerization, producing fibrils coated
      with fatty acrylate polymers. The proposed modification targets a change in the
      interfibrillar interactions and improved CNF compatibility with a degradable
      plastic composite matrix, poly(butylene adipate- co-terephthalate), PBAT in
      composites prepared by melt extrusion. CNF had a clear reinforcing effect on
      PBAT, increasing Young's modulus by at least 35% and 169% at 5 and 20% (w/w) CNF
      content, respectively. However, unmodified CNF showed aggregation, poor adhesion
      in the matrix, and severely impaired the ductility of PBAT. CNF modified by
      admicellar polymerization was homogeneously dispersed in the PBT matrix and
      showed significantly better preservation of the elongation properties compared to
      unmodified CNF, especially at 5% (w/w) addition level.

PMID- 30301348
TI  - Biomimetic Mineralization of Three-Dimensional Printed Alginate/TEMPO-Oxidized
      Cellulose Nanofibril Scaffolds for Bone Tissue Engineering.
AB  - The three-dimensional (3D) printed scaffolds were prepared by partial cross
      linking of TEMPO-oxidized cellulose nanofibril/alginate hydrogel using calcium
      ions for printing the hydrogel while maintaining its shape, fidelity, and
      preventing the collapse of the filaments. The prepared scaffolds were fully cross
      linked using calcium ions immediately after printing to provide the rigidity of
      the hydrogel and give it long-term stability. The composition of the prepared
      pastes was adjusted in view of the description of the hydrogel and 3D printing
      parameters. The rheological properties in terms of thixotropic behavior and
      viscosity recovery of hydrogels were investigated by performing steady shear rate
      experiments. The results show that the viscosity recovery for pure alginate
      hydrogel was only about 16% of the initial value, whereas it was 66% when adding
      cellulose nanofibrils to alginate. Consequently, the shape of the pure alginate
      scaffold was soft and easy to collapse contrarily to the composite scaffold. The
      biomimetic mineralization process of printed scaffolds using simulated body
      fluid, mimicking the inorganic composition of human blood plasma, was performed
      and the hydroxyapatite nucleation on the hydrogel was confirmed. The strength
      properties of the fabricated scaffolds in terms of compressive strength analysis
      were also investigated and discussed. The results show that the alginate/TEMPO
      oxidized cellulose nanofibril system may be a promising 3D printing scaffold for
      bone tissue engineering.

PMID- 30301349
TI  - Design, Synthesis, and Pharmacological Characterization of Carbazole Based
      Dopamine Agonists as Potential Symptomatic and Neuroprotective Therapeutic Agents
      for Parkinson's Disease.
AB  - We have developed a series of carbazole-derived compounds based on our hybrid
      D2/D3 agonist template to design multifunctional compounds for the symptomatic
      and disease-modifying treatment of Parkinson's disease (PD). The lead molecules (
      )-11b (D-636), (-)-15a (D-653), and (-)-15c (D-656) exhibited high affinity for
      both D2 and D3 receptors and in GTPgammaS functional assay, the compounds showed
      potent agonist activity at both D2 and D3 receptors (EC50 (GTPgammaS); D2 = 48.7
      nM, D3 = 0.96 nM for 11b, D2 = 0.87 nM, D3 = 0.23 nM for 15a and D2 = 2.29 nM, D3
      = 0.22 nM for 15c). In an animal model of PD, the test compounds exhibited potent
      in vivo activity in reversing hypolocomotion in reserpinized rats with a long
      duration of action compared to the reference drug ropinirole. In a cellular
      antioxidant assay, compounds (-)-11b, (-)-15a, and (-)-15c exhibited potent
      activity in reducing oxidative stress induced by neurotoxin 6-hydroxydopamine (6
      OHDA). Also, in a cell-based PD neuroprotection model, these lead compounds
      significantly increased cell survival from toxicity of 6-OHDA, thereby producing
      a neuroprotective effect. Additionally, compounds (-)-11b and (-)-15a inhibited
      aggregation and reduced toxicity of recombinant alpha synuclein protein in a cell
      based in vitro assay. These observations suggest that the lead carbazole-based
      dopamine agonists may be promising multifunctional molecules for a viable
      symptomatic and disease-modifying therapy of PD and should be further
      investigated.

PMID- 30301350
TI  - Compound Molecular Logic in Accessing the Active Site of Mycobacterium
      tuberculosis Protein Tyrosine Phosphatase B.
AB  - Protein tyrosine phosphatase B (PtpB) from Mycobacterium tuberculosis (Mtb)
      extends the bacteria's survival in hosts and hence is a potential target for Mtb
      specific drugs. To study how Mtb-specific sequence insertions in PtpB may
      regulate access to its active site through large-amplitude conformational
      changes, we performed free-energy calculations using an all-atom explicit solvent
      model. Corroborated by biochemical assays, the results show that PtpB's active
      site is controlled via an "either/or" compound conformational gating mechanism,
      an unexpected discovery that Mtb has evolved to bestow a single enzyme with such
      intricate logical operations. In addition to providing unprecedented insights for
      its active-site surroundings, the findings also suggest new ways of inactivating
      PtpB.

PMID- 30301351
TI  - Comparison of the Effects and Inhibitory Pathways of the Constituents from
      Gynostemma pentaphyllum against LPS-Induced Inflammatory Response.
AB  - Saponins, the primary phytochemicals contributing to the health properties of G.
      pentaphyllum were frequently studied. However, compounds responsible for its
      bioactivities were still poorly understood. The saponin-rich fraction (GPMS), 3-
      O-[2G-( E)-Coumaroyl-3G- O-beta-d-glucosyl-3R- O-beta-d-glucosylrutinoside]
      (KCGG), gypenoside XLVI and gypenoside L were obtained by purification of G.
      pentaphyllum. The compounds were examined and compared with GPMS for their
      inhibitory effects on LPS-induced nitric oxide (NO) production. GPMS and KCGG
      differed in their inhibitory capacities against pro-inflammatory cytokines
      secretion. GPMS exhibited strong inhibition on inducible nitric oxide synthase
      (iNOS) and interleukin-6 (IL-6) mRNA expression but weak inhibition on tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-1beta mRNA expression. KCGG was
      better at inhibiting iNOS, IL-6, TNF-alpha, and cyclooxygenase-2 (COX-2) mRNA
      expression. GPMS showed similar inhibitory potency on mitogen-activated protein
      kinase phosphorylation and nuclear factor-kappaB (NF-kappaB) activation, as
      evidenced by their regulatory effects on LPS-induced P65 phosphorylation, NF
      kappaB nuclear translocation, IkappaBalpha phosphorylation and degradation,
      IkappaKalpha/beta phosphorylation, c-Jun N-terminal kinase phosphorylation, P38
      phosphorylation, and COX-2 expression. KCGG was more powerful in inhibiting the
      NF-kappaB pathway, suggesting that KCGG might be used in the management of
      inflammatory-associated diseases in which NF-kappaB played pivotal roles.
      Furthermore, KCGG might be mainly responsible for the predominant effects of
      GPMS.

PMID- 30301352
TI  - Orientation Relaxation Dynamics in Cellulose Nanocrystal Dispersions in the
      Chiral Liquid Crystalline Phase.
AB  - A Landau-de Gennes formulation was implemented in dynamic finite element
      simulations to compare with postshear relaxation experiments that were conducted
      on cholesteric cellulose nanocrystal (CNC) dispersions. Our study focused on the
      microstructural reassembly of CNCs in lyotropic dispersions as parameters such as
      chiral strength and gap confinement were varied. Our simulation results show that
      homeotropic and/or more complicated three-dimensional helical configurations are
      possible, depending on the choice of these parameters. We also observed how
      dynamic banding patterns develop into the hierarchical microstructures that are
      characterized by an equilibrium pitch length in both the experiments and
      simulations. This work has immediate relevance for cellulose nanocrystal
      dispersion processing and provides new insight into fluid phase ordering for
      tailorable optical properties.

PMID- 30301353
TI  - Amphiphilic Cellulose Nanocrystals for Enhanced Pickering Emulsion Stabilization.
AB  - Sulfated cellulose nanocrystals (CNC) with high surface charge density are
      inadequate for stabilizing oil-water emulsions, which limits their applications
      as interfacial stabilizers. We performed end-group modification by introducing
      hydrophobic chains (polystyrene) to CNC. Results showed that the modified CNC are
      more effective in emulsifying toluene and hexadecane than pristine CNC. Various
      parameters were investigated, such as concentration of particles, electrolytes,
      and polarity of solvents on the characteristics of the emulsions. This study
      provides strategies for the modification of cellulose nanocrystals to yield
      amphiphilic nanoparticles that enhance the stability of emulsions. Such systems,
      bearing biocompatible and environmentally friendly characteristics, are
      attractive for use in a wide range of industries spanning food, biomedicine,
      pharmaceuticals, cosmetics, and petrochemicals.

PMID- 30301354
TI  - Copper-Catalyzed Unstrained C-C Single Bond Cleavage of Acyclic Oxime Acetates
      Using Air: An Internal Oxidant-Triggered Strategy toward Nitriles and Ketones.
AB  - A copper-catalyzed aerobic oxidative C-C single bond cleavage of acyclic
      unstrained oxime acetates is reported, providing various aryl nitriles and
      ketones in good yields. Mechanistic studies indicate a radical procedure is
      involved in this transformation, and the oxygen atom in the ketone products is
      originated from O2 in the air. Oxime acetates as an internal oxidant have been
      proved to be an initiator, which may promote the discovery of novel protocol for
      C-C bond cleavage and dioxygen activation.

PMID- 30301355
TI  - Introduction: Carbene Chemistry.

PMID- 30301357
TI  - The patterns of self-reported maternal complications in Indonesia: are there
      rural-urban differences?
AB  - INTRODUCTION: Specific and targeted intervention is needed to reduce the
      relatively high maternal mortality and morbidity in Indonesia. The apparent rural
      urban disparities might require different intervention strategies. Therefore,
      this study aims to assess patterns and sociodemographic determinants of self
      reported maternal morbidity in rural and urban areas. METHODS: Data from the
      Indonesian Demographic and Health Survey 2012 were analyzed. In this cross
      sectional survey, maternal morbidity status and sociodemographic factors were
      obtained through questionnaire-based interviews. Women who completed the maternal
      morbidity questionnaire were included in the analyses (n=12 679). Descriptive
      statistics were used to assess differences in proportion; mixed-effects
      regression was used to evaluate the association between sociodemographic factors
      and maternal morbidity. RESULTS: Approximately 53.3% of women reported
      experiencing pregnancy and/or labor complications, with a lower proportion in
      rural areas (51.3%) than in urban areas (55.1%). The patterns of pregnancy
      morbidities were similar for rural and urban women. The highest proportion of
      pregnancy morbidity was classified as 'other', followed by 'bleeding'. There were
      slight differences in the type of labor morbidities. Compared to urban women,
      women in rural areas had a higher prevalence of bleeding and infection, but a
      significantly lower prevalence of pregnancy rupture of membrane. Nulliparity was
      a dominant factor for self-reported maternal morbidity. Younger urban, but not
      rural, women represented a higher proportion of maternal morbidity. In urban
      areas, women with social disadvantage represented a higher proportion of
      morbidity. However, in rural areas, a higher prevalence of maternal morbidity was
      seen in women of higher socioeconomic status. These rural-urban disparities might
      be partially caused by differences in knowledge of maternal morbidities and
      sociodemographic status between rural and urban women. CONCLUSIONS: This study
      found similar patterns of pregnancy morbidity, but slight differences in labor
      morbidity patterns. Specific interventions for major maternal complications
      within rural or urban areas are important. There were also differences in the
      proportion of self-reported maternal complications by sociodemographic factors,
      which might be caused by differences in reporting. Intervention to improve
      knowledge and awareness of maternal complication is needed, specifically for
      socially disadvantaged women and women living in rural areas.

PMID- 30301358
TI  - Effects of Hand Exercise on Eating Action in Patients With Alzheimer's Disease.
AB  - We aim to investigate whether a popular hand exercise could be used to improve
      the action of eating in patients with Alzheimer's disease (AD). A 6-month
      intervention was conducted in 60 patients with AD who live in a nursing home.
      They were divided into hand exercise and control groups. Patients of the control
      group maintained their daily routine. The improvement of Edinburgh Feeding
      Evaluation in Dementia scale in hand exercise group was significantly greater
      than in the control group ( P = .003). Significant differences in time of
      autonomous eating and time of simulated eating between patients in the hand
      exercise and control groups ( P < .05) were noted. The improvements in accuracy
      of eating action and coordination of eating action from baseline were significant
      in hand exercise group compared to the control group ( P = .020 and .014,
      respectively). Hand exercise is a safe and effective intervention to improve the
      feeding and eating of people with AD.

PMID- 30301360
TI  - A decade of incurred sample reanalysis: failures, investigations and impact.
AB  - Incurred sample reanalysis (ISR) is used to ensure the validity and reliability
      of bioanalytical data. Additionally, ISR results also help identify issues that
      could influence or bias the data. Overall, based on a decade of experimental data
      generated at Eli Lilly and Company, ISR failures are few with less than 5% of ISR
      samples failing to meet acceptance criteria. In a majority of situations, the
      cause for ISR failures has been 'human-error.' However, there are examples where
      ISR has helped identify issues related to the stability of the analyte or the
      ruggedness of the method. As a strategy, it is beneficial to conduct ISR
      following the completion of a few sample runs, so any potential issues impacting
      the validity and reliability of the data can be identified and rectified early.

PMID- 30301359
TI  - Prevalence and predictors of electrocardiogram abnormalities among athletes.
AB  - Background Existing evidence, predominantly from Western countries, has
      demonstrated that athletes' hearts undergo structural, physiological, and
      electrical changes, leading to abnormal electrocardiogram readings that are said
      to be training-related. Athletes with non-training-related electrocardiographic
      abnormalities risk developing sudden cardiac death. The lack of studies on this
      issue in the Asian population warrants further exploration. Therefore, the aim of
      this study was to estimate the prevalence and predictive factors contributing to
      electrocardiogram abnormalities among athletes in Brunei. Methods A descriptive
      cross-sectional study was conducted on 100 athletes (median age 25.2 years) in 10
      sporting disciplines, whose electrocardiogram readings and essential information
      was obtained. Results The prevalence of an abnormal electrocardiogram was 52%
      (95% confidence interval: 42.0%-62.0%), comprising training-related changes in
      49% (95% confidence interval: 39.0%-59.0%) and non-training-related changes in 3%
      (95% confidence interval: 0.4%-6.4%). Athletes with a higher body mass index were
      3.3-times (95% confidence interval: 1.47-9.58) more likely to have abnormal
      electrocardiogram readings. Athletes <25-years old (odds ratio = 0.25, 95%
      confidence interval: 0.07-0.81) and those who trained with low dynamic intensity
      (odds ratio = 0.33, 95% confidence interval: 0.12-0.93) were significantly less
      likely to have electrocardiogram abnormalities. Conclusions This is the first
      study reporting abnormal electrocardiograms among athletes in Brunei, which
      provides important information to relevant agencies involved in the preparation
      of Asian athletes for domestic or international competitions, particularly those
      with a higher body mass index and low dynamic training intensity.

PMID- 30301361
TI  - Incurred sample reanalysis: 'too much of a good thing?'

PMID- 30301362
TI  - Application of Integrative Metacognitive Psychotherapy for Serious Mental
      Illness.
AB  - Recovery for many people with serious mental illness is more than symptom
      remission or attainment of certain concrete milestones. It can also involve
      recapturing a previously lost coherent and cohesive sense of self. The authors
      review several case studies of integrative metacognitive psychotherapy offered to
      adults with broadly differing clinical presentations. In all the cases, patients
      demonstrated significant subjective gains and objective improvements-for example,
      in negative symptoms, in substance use, and in overcoming a history of childhood
      sexual abuse. By applying this method to various problems-issues consistent with
      the realities faced in actual clinics-the authors explore how integrative
      metacognitive psychotherapy is able to address more subjective aspects of
      recovery by stimulating gains in the experience of agency that lead to the
      development of more cohesive self-experience, regardless of objective markers of
      recovery.

PMID- 30301363
TI  - Home Hospice Caregivers' Perceived Information Needs.
AB  - BACKGROUND: Although home hospice organizations provide essential care for and
      support to terminally ill patients, many day-to-day caregiving responsibilities
      fall to informal (ie, unpaid) caregivers. Studies have shown that caregivers
      value receiving clear information about end-of-life (EoL) care. Meeting the
      information needs of this group is critical in improving their experience in
      hospice. OBJECTIVES: To identify the information needs of informal home hospice
      caregivers. DESIGN: One hundred five semi-structured phone interviews with
      informal caregivers were conducted. Study data were analyzed using a standard
      qualitative method (ie, content analysis). PARTICIPANTS: Informal home hospice
      caregivers whose loved ones have been discharged (death or live discharge) from
      an urban, nonprofit hospice organization. Measured: Participants' information
      needs were ascertained by assessing whether information regarding hospice was or
      was not fully explained or whether there was information they wished they knew
      prior to the hospice transition. RESULTS: Among study participants, 48.6% had
      unmet information needs related to (1) general information about hospice (n = 17,
      16.2%), (2) what to expect at the EoL (n = 19, 18.1%), and (3) support provided
      by hospice (n = 30, 28.6%). Specifically, caregivers expressed the need for more
      information on what hospice is, caring for a dying patient, and the day-to-day
      care hospice provides. CONCLUSION: Our study indicates that approximately half of
      the informal caregivers had unmet information needs. Further research is needed
      to identify efficacious strategies to best meet the information needs of this
      group. Specific topics that need emphasis include what hospice care is, what to
      expect at the EoL, and what level of support hospice offers.

PMID- 30301364
TI  - ISR: what have we learned after a decade of experience?
AB  - Within our company, incurred sample reproducibility (ISR) was implemented a
      decade ago. Only 11 studies (<2%) with failed ISR were identified over that
      period. These cases are described along with the strategy followed to resolve the
      issue. For three studies the failing ISR was caused by a method failure and all
      instances could be traced back to an instability problem. The majority of the
      failed ISR experiments were due to human error. For most of the studies the issue
      could be resolved and results reported. In two studies, no valid results could be
      generated. Based on this analysis we advise to limit the number of studies that
      require ISR assessment.

PMID- 30301365
TI  - How Low-Income Smokers in New York Access Cheaper Cigarettes.
AB  - PURPOSE: To understand the tobacco acquisition practices of low-income smokers in
      New York State in light of high cigarette prices due to high cigarette taxes.
      DESIGN: Eight focus groups with low-income smokers were conducted in spring 2015
      and 2016 (n = 74). SETTING: New York City (NYC) and Buffalo, New York.
      PARTICIPANTS: Low-income adults aged 18 to 65 who smoke cigarettes regularly.
      METHOD: Qualitative analysis of focus group transcripts that explored differences
      and similarities by region. We used the interview guide-which covered the process
      of acquiring cigarettes and the impact of cigarette prices-as a framework for
      analysis to generate themes and subthemes (deductive coding). We also generated
      themes and subthemes that emerged during focus group discussions (inductive
      coding). RESULTS: Some smokers in Western New York have switched to untaxed
      cigarettes from Native American reservations, whereas low-income smokers in NYC
      described convenient sources of bootlegged cigarettes (packs or loosies) in their
      local neighborhood stores, through acquaintances, or on the street. Familiarity
      with the retailer was key to accessing bootlegged cigarettes from retailers.
      CONCLUSIONS: Smokers in this study could access cheaper cigarettes, which
      discouraged quit attempts and allowed them to continue smoking. The availability
      of lower priced cigarettes may attenuate public health efforts aimed at reducing
      smoking prevalence through price and tax increases.

PMID- 30301367
TI  - Effects of exercise on the physical fitness level of adults with intellectual
      disability: a systematic review.
AB  - PURPOSE: To systematically review the existing scientific evidence regarding the
      effects of physical exercise on the fitness level of people with intellectual
      disabilities. METHODS: Following the checklist of the Preferred Reporting Items
      for Systematic review and Meta-Analysis Protocols, the PubMed, CINAHL,
      SPORTDiscus, and Scopus databases were searched using specific keywords up to
      January 2018. The methodological quality of the studies found was rated by the
      means of specific scales according to their specific design. RESULTS: A total of
      44 studies were selected. The majority of the included studies were randomized
      controlled trials (n = 17), followed by non-controlled studies (n = 11), non
      randomized controlled trials (n = 10), and comparative studies (n = 6). Aerobic,
      strengthening, and combined exercise programs were the most frequently proposed
      interventions. Exercise showed to have significant effects on the
      cardiorespiratory and muscular fitness. Not all the selected studies reported
      improvements in parameters related to body composition. CONCLUSIONS: There is
      sufficient scientific evidence for the beneficial effects of exercise on the
      cardiovascular and muscular fitness of adults with mild/moderate ID. There is a
      need for more studies focused on the impact of physical exercise on the body
      composition of this population, and those that aim at identifying the impact of
      alternative interventions. IMPLICATIONS FOR REHABILITATION There is a need for
      basic guidelines that can help rehabilitation professionals to prescribe exercise
      for maintaining and improving physical fitness in the adults with intellectual
      disabilities. In adults with intellectual disabilities, aerobic exercise has
      beneficial effects on cardiovascular and muscular fitness, flexibility, and range
      of motion. No firm conclusion can be made regarding the effects of aerobic,
      muscular, and combined training programs on the body composition of adults with
      intellectual disabilities. Rehabilitation professionals should be aware that
      scientific evidence regarding the prescription of alternative exercise protocols
      in adults with intellectual disabilities (i.e. dancing, water-based exercise,
      animal therapy, etc) is scarce.

PMID- 30301366
TI  - Perirenal Fat: A Unique Fat Pad and Potential Target for Cardiovascular Disease.
AB  - Although visceral obesity is recognized as a risk factor for cardiovascular
      diseases (CVDs), the efficacy of omental fat removal in CVD treatment is still
      controversial. There is a need to identify other visceral fat depots for CVD
      management. This review aims to provide a summary on perirenal fat as an
      important risk factor for CVD. Studies on epidemiology, anatomy, and function of
      perirenal fat were reviewed. Observational studies in humans suggest that
      excessive perirenal fat increases the risk of hypertension and coronary heart
      disease. Anatomy studies prove that perirenal fat is unique compared to other
      connective tissues in that it is well vascularized, innervated, and drains into
      the lymphatic system. Other special morphological features include a complete
      fascia border, sympathetic-independent development of architecture, and proximity
      to the kidneys. Based on these anatomical features, perirenal fat regulates the
      cardiovascular system presumably via neural reflex, adipokine secretion, and fat
      kidney interaction. These new insights suggest that perirenal fat may constitute
      a promising target for CVD management.

PMID- 30301368
TI  - Advances in stem cell therapy for erectile dysfunction.
AB  - INTRODUCTION: Stem cell (SC) application is a promising area of research in
      regenerative medicine, with the potential to treat, prevent, and cure disease. In
      recent years, the number of studies focusing on SCs for the treatment of erectile
      dysfunction (ED) and other sexual dysfunctions has increased significantly. Areas
      covered: This review includes critical ED targets and preclinical studies,
      including the use of SCs and animal models in diabetes, aging, cavernous nerve
      injury, and Peyronie's disease. A literature search was performed on PubMed for
      English articles. Expert opinion: Combination treatment offers better results
      than monotherapy to improve pathological changes in diabetic ED. Regenerative
      medicine is a promising approach for the maintenance of sexual health and
      erectile function later in life. Cavernous nerve regeneration and vascular
      recovery employing SC treatment may be focused on radical prostatectomy-induced
      ED. Notwithstanding, there are a number of hurdles to overcome before SC-based
      therapies for ED are considered in clinical settings. Paracrine action, not
      cellular differentiation, appears to be the principal mechanism of action
      underlying SC treatment of ED. Intracavernosal injection of a single SC type
      should be the choice protocol for future clinical trials.

PMID- 30301369
TI  - GZD2202, a novel TrkB inhibitor, suppresses BDNF-mediated proliferation and
      metastasis in neuroblastoma models.
AB  - Collective data suggest tropomyosin-related kinase B (TrkB), which is correlated
      with the growth, migration and poor prognosis of neuroblastoma (NB), is a
      potential target for NB target therapy. Several Phase I/II pan-Trk inhibitors
      display impressive clinical outcomes but still no drug has been approved for
      general use. In this paper, we report a novel structural TrkB inhibitor GZD2202,
      a structural derivative of our previously identified DDR1 antagonists. GZD2202
      demonstrates a moderate selectivity between Trk B/C and TrkA. GZD2202 suppresses
      the brain-derived neurotrophic factor (BDNF) -mediated TrkB signalling pathway,
      proliferation, migration and invasion in SH-SY5Y-TrkB neuroblastoma cells, and
      causes about 36.1% growth inhibition in a SH-SY5Y-TrkB neuroblastoma xenograft
      model.

PMID- 30301370
TI  - Objective ocular surface tolerance in patients with glaucoma treated with topical
      preserved or unpreserved prostaglandin analogues.
AB  - PURPOSE: Preservatives in glaucoma medications have been associated with ocular
      toxicity. We compared ocular signs and symptoms in patients with open-angle
      glaucoma or ocular hypertension treated in monotherapy with preserved or
      preservative-free prostaglandin analogues. METHODS: Observational cross-sectional
      clinical study in real life. 82 patients treated for at least 6 months with
      prostaglandin analogue were assessed for intraocular pressure, ocular symptoms
      and ocular signs including conjunctival hyperaemia, tear break-up time and tear
      meniscus height measured using objective and non-invasive methods (OCULUS
      Keratograph 5M). Patients presenting with symptoms of ocular toxicity with
      preserved prostaglandin analogues were switched to preservative-free latanoprost,
      and a second assessment was processed 6 months after. RESULTS: At inclusion, 30
      (36.6%) patients were treated with preservative-free latanoprost, 25 (30.5%) with
      preserved latanoprost, 16 (19.5%) with preserved travoprost and 11 (13.4%) with
      preserved bimatoprost. Patients treated with preservative-free latanoprost
      reported significantly less ocular symptoms upon instillation (mainly burning)
      and between instillations than patients treated with preserved prostaglandin
      analogues. The mean conjunctival hyperaemia (limbal + bulbar) was significantly
      lower with preservative-free latanoprost (2.08 +/- 0.55) compared to preserved
      latanoprost (2.50 +/- 0.7, p = 0.0085), preserved travoprost (2.67 +/- 0.82, p =
      0.0083) and preserved bimatoprost (2.68 +/- 0.67, p = 0.0041). There were no
      relevant between-group differences in mean tear meniscus height and break-up
      time. Ocular symptoms and conjunctival hyperaemia improved when preserved
      prostaglandin analogues were switched to preservative-free latanoprost for 6
      months while intraocular pressure reduction was maintained. CONCLUSION: Overall,
      this study suggests a better subjective and objective ocular tolerance when
      patients were treated with preservative-free latanoprost than with other
      preserved prostaglandin analogues monotherapy. Switching to preservative-free
      latanoprost maintained intraocular pressure at the same level as preservative
      prostaglandin analogue, but improved ocular surface tolerance.

PMID- 30301371
TI  - Pre-exposure prophylaxis sorting among men who have sex with men.
AB  - Factors such as race, masculinity, and sexually transmitted infections have been
      documented to influence partner selection in men who have sex with men (MSM). Pre
      exposure prophylaxis (PrEP) has received mixed evaluations as a responsible step
      in HIV prevention and as an enabler of risker sexual practices. PrEP may
      consequently serve as an additional factor in partner choice. We examine the role
      that PrEP use and "promiscuity" play in affiliation and dating decisions by men
      who have sex with men with different HIV and PrEP stati. We invited 450 MSM
      across the United States from a smartphone geo-locating sex application to
      complete a survey of which 339 successfully finished the task. The survey
      contained vignettes of fictional men who were promiscuous or monogamous and
      either taking PrEP or not. Participants provided responses on whether to
      affiliate with these characters in three social domains: as friends, dates, or
      sex partners. Neither PrEP nor promiscuity influenced friendship choices. There
      was a preference for dating monogamous characters. Critically, PrEP influenced
      sexual affiliations for HIV negative individuals who showed a preference for PrEP
      using characters. The pattern of results provides quantitative evidence for PrEP
      based sexual sorting aimed at reducing risk of HIV transmission.

PMID- 30301372
TI  - Beyond BCG: the approaching era of personalised bladder-sparing therapies for non
      muscle-invasive urothelial cancers.
AB  - Progress in the management of non-muscle invasive bladder cancer has been slow.
      Despite longstanding use of intravesical therapies (e.g., Bacille Calmette
      Guerin, BCG) to complement cystoscopic resection of high-grade lesions, many
      patients still develop recurrences requiring cystectomy, while others suffer side
      effects of BCG without definite benefit. Many questions remain: for example, how
      many patients receive intravesical prophylaxis without efficacy? Which high-risk
      patients are best managed with early cystectomy? Could systemic therapies and/or
      radiotherapy extend bladder preservation times? Such questions may soon be
      refined by clinicopathologic non-muscle invasive bladder cancer signatures that
      predict sensitivity to cytotoxic, immune and targeted therapies. Hypothesis-based
      trials using these signatures should lead to more rational adjuvant treatments,
      longer bladder preservation times, and better quality of life for patients.

PMID- 30301373
TI  - Hypersensitivity and infusion-site adverse events with intravenous fosaprepitant
      after anthracycline-containing chemotherapy: a retrospective study.
AB  - AIM: Fosaprepitant, an intravenous neurokinin-1 receptor antagonist for
      chemotherapy-induced nausea and vomiting, contains polysorbate 80, which is
      associated with infusion-site adverse events (ISAEs) and hypersensitivity
      systemic reactions (HSRs). This study investigated ISAEs/HSRs following
      fosaprepitant with anthracycline-containing chemotherapy. PATIENTS & METHODS:
      This retrospective chart review noted ISAEs/HSRs following the anthracycline
      doxorubicin+cyclophosphamide and a three-drug fosaprepitant regimen, via
      peripheral line. RESULTS: 35/127 patients (28%) developed ISAEs/HSRs with
      chemotherapy and antiemetic therapy: 32 developed 137 individual ISAEs, primarily
      erythema, pain and catheter-site swelling; 16 developed 50 individual HSRs,
      primarily edema/swelling, erythema or dermatitis (no anaphylaxis). CONCLUSION:
      Fosaprepitant is associated with a significant ISAE/HSR rate following
      anthracycline-containing chemotherapy via peripheral line. Polysorbate 80-free
      intravenous neurokinin-1 receptor antagonist may provide a safer chemotherapy
      induced nausea and vomiting prophylaxis option.

PMID- 30301374
TI  - Optical coherence tomography angiography findings in a case with acute posterior
      multifocal placoid pigment epitheliopathy.
AB  - Twenty-six-year-old male patient admitted to the outpatient clinic with a
      complaint of decreased vision in both eyes. Visual acuity was 2/10 in the right
      and 7/10 in the left eye. Fundus examination revealed bilateral yellow-white
      subretinal lesions involving the macula. Fluorescein angiography showed
      hypofluorescent lesions in early and hyperflourescent lesions in the late phase.
      Optical coherence tomography angiography performed in the acute phase showed
      bilateral hypofluorescency at the choriocapillary level. A diagnosis of acute
      posterior multifocal placoid pigment epitheliopathy was given. After steroid
      treatment, visual acuity was improved to 10/10 and earlier lesions in optical
      coherence tomography angiography were found to be reduced. In conclusion, optical
      coherence tomography angiography is a noninvasive imaging technique that can be
      used in the diagnosis and follow-up of acute posterior multifocal placoid pigment
      epitheliopathy.

PMID- 30301375
TI  - Optimal Allocation of Interviews to Baseline and Endline Surveys in Place-Based
      Randomized Trials and Quasi-Experiments.
AB  - BACKGROUND: Many place-based randomized trials and quasi-experiments use a pair
      of cross-section surveys, rather than panel surveys, to estimate the average
      treatment effect of an intervention. In these studies, a random sample of
      individuals in each geographic cluster is selected for a baseline
      (preintervention) survey, and an independent random sample is selected for an
      endline (postintervention) survey. OBJECTIVE: This design raises the question,
      given a fixed budget, how should a researcher allocate resources between the
      baseline and endline surveys to maximize the precision of the estimated average
      treatment effect? RESULTS: We formalize this allocation problem and show that
      although the optimal share of interviews allocated to the baseline survey is
      always less than one-half, it is an increasing function of the total number of
      interviews per cluster, the cluster-level correlation between the baseline
      measure and the endline outcome, and the intracluster correlation coefficient. An
      example using multicountry survey data from Africa illustrates how the optimal
      allocation formulas can be combined with data to inform decisions at the planning
      stage. Another example uses data from a digital political advertising experiment
      in Texas to explore how precision would have varied with alternative allocations.

PMID- 30301376
TI  - Psychometric Testing of the Evidence-Based Practice Nursing Leadership Scale and
      the Work Environment Scale After Cross-Cultural Adaptation in Mainland China.
AB  - Implementation and sustainability of the evidence-based practice (EBP) approach
      within systems of health-care delivery require leadership and organizational
      support, yet few instruments have been developed specifically in Mainland China.
      The purpose of this study was to adapt the EBP Nursing Leadership Scale and the
      EBP Work Environment Scale to Mainland China's cultural context and to evaluate
      the psychometric properties of the newly adapted Chinese version. A pilot study
      was conducted in Mainland China with 25 clinical nurses. A subsequent validation
      study was conducted with 419 nurses from Mainland China. A content validity index
      of .985 and .982 was achieved. The split-half coefficient was .890 for the EBP
      Nursing Leadership Scale and .892 for the EBP Work Environment Scale. Test-retest
      reliability was .871 and .855, respectively. Principal component analysis
      resulted in a one-factor structure explaining 62.069% of the total variance for
      the EBP Nursing Leadership Scale and 62.242% of the total variance for the EBP
      Work Environment Scale. Both of the newly cross-culturally adapted scales possess
      adequate internal consistency and test-retest reliability and validity and
      therefore may be utilized in health-care environments to assess leadership and
      organizational support for EBP in Mainland China.

PMID- 30301377
TI  - Mass spectral studies of N-oxides of chemical weapons convention-related
      aminoethanols by gas chromatography/mass spectrometry after silylation.
AB  - N-Alkylaminoethanols, N,N'-dialkylaminoethanols, and triethanolamine are the
      hydrolyzed products or precursors of V-agents/nitrogen mustards. These compounds
      are prone to undergo oxidation in environmental matrices. Detection of the
      oxidized products provides a clue for the presence of parent amine compounds and
      it is an important task in the verification process of chemical weapons
      convention. Gas chromatography/mass spectrometry is the technique of choice for
      the detection of most of the chemical warfare agents; however, it is ideal to
      develop gas chromatography/mass spectrometry techniques for all the possible
      degradation products of chemical warfare agents as well. In general, the N-oxides
      of amines are expected to be thermally unstable; hence, the gas
      chromatography/mass spectrometry analysis of the N-oxides of triethanolamine, N
      alkyldiethanolamines and N,N'-dialkylaminoethanols is not explored. In this
      study, the N-oxides of chemical weapons convention-related aminoethanols (13
      compounds) were successfully silylated and then analyzed by gas
      chromatography/mass spectrometry under electron ionization and chemical
      ionization techniques. The electron ionization mass spectra showed abundant
      molecular ions and structure indicative fragment ions including [M
      (O+CH2CH2OH)]+. The alkyl groups attached to nitrogen resulted in structure
      specific fragment ions that enable differentiation of isomeric compounds. The
      methane/chemical ionization spectra showed considerably abundant [M+H]+ (>10%)
      and the expected adduct ions. The retention indices of all the compounds were
      calculated using Van den Dool's formula. The gas chromatography/mass spectrometry
      data together with retention index values could be used for unambiguous
      identification of the N-oxides of aminoethanols during off-site analysis or
      proficiency tests.

PMID- 30301378
TI  - Challenges of probe cocktail approach for human drug-drug interaction assays.

PMID- 30301379
TI  - New daily persistent headache (NDPH) triggered by a single Valsalva event: A case
      series.
AB  - Objective To describe a new subtype of new daily persistent headache that is
      triggered by a single Valsalva event. Methods A case series of patients was
      evaluated in an academic headache clinic over a 3-year time period. Results A
      total of seven patients (four female and three male) were diagnosed with this new
      subtype of new daily persistent headache. The headaches all began after a single
      Valsalva event. Average age at time of headache onset was 41 years (males: 39
      years; females: 43 years) with an age range of 20-62 years. All patients
      developed their syndrome during the months of September to February with November
      and February being the most cited months (5/7 patients). Immediate worsening in
      the Trendelenburg position occurred in all patients and appeared to be an almost
      diagnostic test for the syndrome. No patient had papilledema on funduscopic exam.
      Five out of seven patients had no prior headache history including cough,
      exercise or migraine. Four of seven patients were of normal weight, while one was
      overweight and two were obese. A crowded posterior fossa was identified in five
      of seven patients on brain MRI. On cerebrospinal fluid pressure/volume lowering
      medication (acetazolamide, indomethacin and/or spironolactone), five out of seven
      patients achieved 90% plus improvement in headache frequency while three patients
      became pain free. Three patients were able to taper off medication without
      headache recurrence. Conclusion New daily persistent headache after a single
      Valsalva event appears to be a unique subtype of new daily persistent headache
      that is responsive to cerebrospinal fluid pressure/volume lowering medications.
      An abnormal reset of cerebrospinal fluid pressure/intracranial pressure to an
      elevated state is the presumed pathogenesis and may relate to the patient's
      baseline neuroanatomy of a crowded posterior fossa. There appears to be a
      circadian periodicity to the onset of the syndrome. Worsening in the
      Trendelenburg position is a probable diagnostic test. Defining new daily
      persistent headache subtypes by triggering event appears to be making a positive
      inroad in the understanding of this condition and helps present new effective
      therapies.

PMID- 30301381
TI  - Predictive value of laryngeal adductor reflex testing in patients with dysphagia
      due to a cerebral vascular accident.
AB  - PURPOSE: To determine the relationship between air pulse vs. touch laryngeal
      adductor reflex (LAR) tests and the clinical sensory findings of fiberoptic
      endoscopic evaluations of swallowing. METHOD: A retrospective review was
      conducted for 43 patients with dysphagia due to stroke that underwent fiberoptic
      endoscopic evaluation of swallowing with sensory testing (FEESST). Each patient
      received LAR testing using air pulse or touch methodologies. Clinically,
      responsiveness to pharyngeal residue and responsiveness to penetration or
      aspiration were analysed. RESULT: The sensitivity, specificity, positive and
      negative predictive values for both LAR test groups indicate that LAR testing did
      not effectively predict sensory function during the clinical swallow evaluation.
      Across both LAR groups, specificity values were higher than sensitivity values.
      In fact, the specificity values for the light touch LAR test group were extremely
      high, but the negative predictive values did not support those findings.
      Sensitivity and positive predictive values were low for both groups. CONCLUSION:
      Although LAR testing provides valuable information regarding laryngeal sensory
      discrimination, the results of the current study suggest that a clinical
      evaluation of swallowing is critical for effectively assessing the way in which
      patients utilise sensory information during swallowing.

PMID- 30301380
TI  - Correlations among brain and spinal MRI findings in spontaneous intracranial
      hypotension.
AB  - OBJECTIVES: Several brain and spinal magnetic resonance imaging signs have been
      described in spontaneous intracranial hypotension. Their correlations are not
      fully studied. This study aimed to explore potential mechanisms underlying
      cerebral neuroimaging findings and to examine associations among spinal and brain
      magnetic resonance imaging signs. METHODS: We conducted a retrospective review of
      magnetic resonance myelography and brain magnetic resonance imaging records of
      patients with spontaneous intracranial hypotension. Categorical principal
      component analysis was employed to cluster brain neuroimaging findings. Spearman
      correlation was employed to analyze associations among different brain
      neuroimaging findings and between brain and spinal neuroimaging findings.
      RESULTS: In patients with spontaneous intracranial hypotension (n = 148),
      categorical principal component analysis of brain neuroimaging signs revealed two
      clusters: Cerebral venous dilation and brain descent. Among all brain magnetic
      resonance imaging signs examined, only midbrain-pons angle associated with
      anterior epidural cerebrospinal fluid collection length (surrogate spinal
      cerebrospinal fluid leak severity) (n = 148, Spearman's rho = -0.38, p < .001).
      Subgroup analyses showed that the association between midbrain-pons angle (within
      brain descent cluster) and spinal cerebrospinal fluid leak severity was presented
      in patients with convex margins of the transverse sinuses (n = 122, Spearman's
      rho = -0.43, p < .001), but not in patients without convex margins (n = 26,
      Spearman's rho = -0.19, p = .348). The association between severity of transverse
      sinus distension and spinal cerebrospinal fluid leak severity was only presented
      in patients without convex margins (n = 26, Spearman's rho = 0.52, p = .006).
      CONCLUSION: This study indicates that there are two factors behind the brain
      neuroimaging findings in spontaneous intracranial hypotension: Cerebral venous
      dilation and brain descent. Certain brain neuroimaging signs correlate with
      spinal cerebrospinal fluid leakage severity, depending on different
      circumstances.

PMID- 30301382
TI  - Novel technology for mobility and balance tracking in patients with multiple
      sclerosis: a systematic review.
AB  - INTRODUCTION: Mobility and balance impairments in patients with multiple
      sclerosis (MS) are major factors for decreased quality of life. Novel sensing
      technologies have great potential to efficiently capture subtle changes in
      mobility and balance performance, and thus improve current practices by providing
      an easy-to-implement, objective, and continuous functional tracking in MS
      population. Areas covered: This review details the collective findings of novel
      technology utilization in mobility and balance tracking in patients with MS.
      Thirty-three were systematically identified and included in this review.
      Pertinent methodological features (participant demographics, sensing technology,
      study aims, functional assessment protocols, and outcome measures) were extracted
      from each article. The construct validity, reliability, clinical relevance, and
      discriminative ability of sensor-based assessment in the MS population were
      summarized. Expert commentary: Sensor-based balance and mobility assessment are
      valid in comparison with reference standard techniques and are reliable to
      measure performance in the MS population. Sensor-based measures are also
      associated with validated clinical outcomes and are sensitive to functional
      deficits in individuals with MS. Such technologies may greatly improve the
      likelihood of detecting mobility and balance dysfunctions in real-world
      environments, thus allowing healthcare professionals to monitor interventions and
      manage disease progression precisely and efficiently Abbreviations: PwMS:
      Patients with Multiple Sclerosis; BBS: Berg Balance Scale; DGI: Dynamic Gait
      Index; ABC: Activity-specific Balance Confidence; T25FW: Timed 25 Foot Walk;
      6MWT: 6 minute walk test; TUG: Timed Up and Go test; EO: Eyes Open; EC: Eyes
      Closed; ICC: Intraclass Correlation Coefficient; EDSS: Expanded Disability Status
      Scale; MFIS: Modified Fatigue Impact Scale; MSWS: Multiple Sclerosis Walking
      Scale; MSIS: Mutliple Sclerosis Impact Scale; PPA: Physiological Profile
      Assessment; HC: Healthy Control; AP: Anterior-posterior direction; ML:
      Mediolateral direction.

PMID- 30301383
TI  - Serum neopterin levels in women with preeclampsia: a systematic review.
AB  - OBJECTIVE: Neopterin is a pteridine that is produced following activation of
      human macrophages upon stimulation with the cytokine interferon-gamma. Several
      studies suggest its association with preeclampsia and the purpose of the present
      study is to evaluate this assumption. METHODS: We searched the Medline (1992
      2018), Scopus (1993-2018) and Google Scholar (1993-2018) databases. All articles
      that evaluated serum neopterin levels in patients with preeclampsia were held
      eligible for inclusion, regardless of the trimester of pregnancy in which the
      measurement was performed. Case reports, animal studies and previous reviews were
      excluded. RESULTS: A total of 10 studies were finally included in the present
      review, with a total number of 3,529 pregnant women. Among them 446 were
      diagnosed with preeclampsia. The majority of included studies reported that serum
      neopterin was significantly higher in patients with preeclampsia, compared to
      normotensive pregnant women (p < .05). One study reported that serum levels seem
      to correlate with the severity of the disease; as patients with HELLP had
      significantly higher values of neopterin compared to patients with mild and
      severe preeclampsia. None of the included studies proposed a cut-off value that
      would help assess the predictive accuracy of this protein for the detection of
      preeclampsia. CONCLUSION: Although current data seem to be promising, neopterin
      remains far from being used in current clinical practice as a biomarker that
      would help predict and follow-up patients that develop preeclampsia. Future
      studies are needed, to determine the optimal timing for its measurement and to
      propose potential cut-off values that would help in this direction.

PMID- 30301385
TI  - Physiologically-based pharmacokinetic modeling for mirabegron: a multi
      elimination pathway mediated by cytochrome P450 3A4, uridine 5'-diphosphate
      glucuronosyltransferase 2B7, and butyrylcholinesterase.
AB  - This was the first study to construct a physiologically-based pharmacokinetic
      (PBPK) model for mirabegron which incorporates the overall elimination pathways
      of metabolism by cytochrome P450 (CYP) 3A4, uridine 5'-diphosphate
      glucuronosyltransferase (UGT) 2B7, and butyrylcholinesterase (BChE) and renal
      excretion. The objective was to assess the risk of drug-drug interactions (DDIs)
      by estimating the contribution of each elimination pathway and simulating the
      magnitude of the DDIs with UGT2B7 inhibitors. A PBPK model for mirabegron was
      constructed to reproduce the plasma concentration-time curves from a phase 1
      study and the magnitude of the DDI with ketoconazole taking into account the
      overall elimination pathways. The PBPK model was subsequently verified using data
      from other DDI studies. The constructed PBPK model estimated the contribution for
      each elimination pathway: 44% and 29% for CYP3A4 and UGT2B7 in the liver, 1.6%
      for UGT2B7 in the kidney, 3.2% for BChE in plasma, and 22% for renal excretion.
      Co-administration of probenecid (an UGT2B7 inhibitor) or fluconazole (an UGT2B7
      and CYP3A4 inhibitor) was predicted to increase area under the curve for
      mirabegron to 115% or 174%, respectively. In conclusion, PBPK modeling and
      simulation revealed a low DDI risk for mirabegron following co-administration
      with BChE or UGT2B7 inhibitors.

PMID- 30301384
TI  - Speech-driven mobile games for speech therapy: User experiences and feasibility.
AB  - PURPOSE: To assist in remote treatment, speech-language pathologists (SLPs) rely
      on mobile games, which though entertaining, lack feedback mechanisms. Games
      integrated with automatic speech recognition (ASR) offer a solution where speech
      productions control gameplay. We therefore performed a feasibility study to
      assess children's and SLPs' experiences towards speech-controlled games, game
      feature preferences and ASR accuracy. METHOD: Ten children with childhood apraxia
      of speech (CAS), six typically developing (TD) children and seven SLPs trialled
      five games and answered questionnaires. Researchers also compared the results of
      ASR to perceptual judgment. RESULT: Children and SLPs found speech-controlled
      games interesting and fun, despite ASR-human disagreements. They preferred games
      with rewards, challenge and multiple difficulty levels. Automatic speech
      recognition-human agreement was higher for SLPs than children, similar between TD
      and CAS and unaffected by CAS severity (77% TD, 75% CAS - incorrect; 51% TD, 47%
      CAS, 71% SLP - correct). Manual stop recording yielded higher agreement than
      automatic. Word length did not influence agreement. CONCLUSION: Children's and
      SLPs' positive responses towards speech-controlled games suggest that they can
      engage children in higher intensity practice. Our findings can guide future
      improvements to the ASR, recording methods and game features to improve the user
      experience and therapy adherence.

PMID- 30301387
TI  - Large Epithelial and Stromal Lesion of Breast: It's Not Always Phyllodes!

PMID- 30301386
TI  - Factors associated with early and late failure after goniotomy for primary
      pediatric glaucoma.
AB  - PURPOSE: To analyze the risk factors associated with early and late failure after
      goniotomy for primary pediatric glaucoma. METHODS: A retrospective study was done
      on infants who underwent goniotomy as the initial surgical procedure for primary
      pediatric glaucoma, and had a follow-up period ?48 months after surgery. Early
      and late failures were defined as intraocular pressure ?18 mmHg or signs of
      glaucoma progression before and after the end of first year, respectively.
      RESULTS: A total of 81 eyes of 47 children were included. The mean age at the
      time of surgery was 6.1 +/- 6.7 months, 34 children (72.3%) were bilateral. The
      mean follow-up was 5.9 +/- 2.8 years. Of the included eyes, 41 eyes (50.6%)
      showed success, 25 eyes (30.9%) showed an early failure, and 15 eyes (18.5%)
      showed a late failure. The mean survival time was 43 months. However, only
      surgery before the end of the first month and positive consanguinity of the
      parents (P < 0.01 for both) were independent risk factors for early and late
      failure of goniotomy for primary pediatric glaucoma. Patients with late failure
      showed a statistically significant lower preoperative intraocular pressure (P =
      0.02). A larger preoperative corneal diameter and a male gender were associated
      with higher but statistically insignificant failure rates. There were no
      differences in the early or late failure rates between unilateral and bilateral
      cases. CONCLUSION: A positive consanguinity of the parents and surgery before the
      end of the first month are the major predictors of failure of goniotomy.

PMID- 30301389
TI  - Phosphoprotein-based drug target activation mapping for precision oncology: a
      view to the future.

PMID- 30301388
TI  - 3,3'-Diindolylmethane enhances apoptosis in docetaxel-treated breast cancer cells
      by generation of reactive oxygen species.
AB  - CONTEXT: A major problem in the treatment of cancer is the development of toxic
      side effects and resistance to chemotherapy. The use of plant compounds to
      overcome resistance and prevent toxicity is a potential strategy for treatment.
      OBJECTIVE: We evaluated whether 3,3'-diindolylmethane (DIM) enhanced the
      sensitivity of breast cancer cells to docetaxel (DOC). MATERIALS AND METHODS: MDA
      MB231 and Sk-BR-3 cells were treated with and without 25 or 50 uM of DIM and 1 nM
      of DOC for 48 and 72 h, respectively. MTT assay was used to measure cell
      survival. Apoptosis and intracellular reactive oxygen species (ROS) were
      determined by flow cytometry. The expression of proteins regulating ROS
      production and apoptosis was evaluated by immunoblotting technique. RESULTS:
      Combining 25 uM of DIM with 1 nM DOC decreased cell survival by 42% in MDA-MB231
      cells and 59% in Sk-BR-3 cells compared to control, DIM, or DOC (p <= 0.05). The
      combination treatment increased apoptosis over 20% (p <= 0.01) in both cell
      lines, which was associated with decreased Bcl-2, increased Bax, cleaved PARP and
      activated JNK (p <= 0.01). ROS production increased by 46.5% in the MDA-MB231 and
      29.3% in Sk-BR-3 cells with the combination compared to DIM or DOC alone.
      Pretreating cells with N-acetyl-cysteine or Tiron abrogated the anti-survival
      effect of the combination. The increase in ROS was associated with a 54% decrease
      in MnSOD and 47% increase in NOX2 protein compared to the other groups.
      CONCLUSIONS: Our findings indicated that DIM enhances the sensitivity of breast
      cancer cells to DOC treatment by increasing ROS, which led to decreased cell
      survival and apoptosis.

PMID- 30301391
TI  - Russell Body Dermatitis Due to Syphilis.

PMID- 30301390
TI  - Dicranopteris linearis extract inhibits the proliferation of human breast cancer
      cell line (MDA-MB-231) via induction of S-phase arrest and apoptosis.
AB  - CONTEXT: Dicranopteris linearis (Burm.f.) Underw. (Gleicheniaceae) has been
      scientifically proven to exert various pharmacological activities. Nevertheless,
      its anti-proliferative potential has not been extensively investigated.
      OBJECTIVE: To investigate the anti-proliferative potential of D. linearis leaves
      and determine possible mechanistic pathways. MATERIALS AND METHODS: MTT assay was
      used to determine the cytotoxic effects of D. linearis methanol (MEDL) and
      petroleum ether (PEEDL) extracts at concentrations of 100, 50, 25, 12.5, 6.25 and
      3.125 ug/mL against a panel of cancer cell lines (breast [MCF-7 and MDA-MB-231],
      cervical [HeLa], colon [HT-29], hepatocellular [HepG2] and lung [A549]), as
      compared to negative (untreated) and positive [5-fluorouracil (5-FU)-treated]
      control groups. Mouse fibroblast cells (3T3) were used as normal cells. The mode
      of cell death was examined using morphological analysis via acridine orange (AO)
      and propidium iodide (PI) double staining. Cell cycle arrest was determined using
      flow cytometer, followed by annexin V-PI apoptosis detection kit. RESULTS: MEDL
      demonstrated the most significant growth inhibition against MDA-MB-231 cells
      (IC50 22.4 ug/mL). PEEDL showed no cytotoxic effect. Induction of apoptosis by
      MEDL was evidenced via morphological analysis and acridine orange propidium
      iodide staining. MEDL could induce S phase cell cycle arrest after 72 h of
      incubation. Early apoptosis induction in MDA-MB-231 cells was confirmed by
      annexin V-FITC and PI staining. Significant increase in apoptotic cells were
      detected after 24 h of treatment with 15.07% cells underwent apoptosis, and the
      amount escalated to 18.24% with prolonged 48 h incubation. CONCLUSIONS: MEDL has
      potential as a potent cytotoxic agent against MDA-MB-231 adenocarcinoma.

PMID- 30301392
TI  - Vocational support in mental health service delivery in Australia.
AB  - BACKGROUND: Individuals experiencing severe and persistent mental illness report
      a desire to gain and sustain work. Individual Placement and Support (IPS) is an
      evidence-based approach to vocational rehabilitation to support competitive
      employment outcomes. AIM/OBJECTIVE: This study aimed to evaluate whether a joint
      governance management partnership, between a clinical adult mental health and an
      employment service, could deliver a sustained IPS program in Australia. MATERIALS
      AND METHOD: The methodology entailed a Clinical Data Mining approach, to examine
      records from seven years of implementation of IPS in one setting within an
      Australian public mental health service context. RESULTS/FINDINGS: Despite the
      prevalence of schizophrenia spectrum diagnoses and an older mean age (39 years),
      indicating that a large proportion of the cohort had experienced serious mental
      illness for over twenty years, findings were that 46.3% of participants achieved
      employment. CONCLUSIONS: This is an excellent result and is comparable to the
      only randomised control trial, with adult services, in the Australian context,
      which found a 42.5% employment rate possible under IPS compared with just 23.5%
      with referral to external employment services. SIGNIFICANCE: More extensive
      trialling of IPS across clinical services is required, in Australia and
      internationally, including fidelity protocols, for knowledge translation to be
      achieved.

PMID- 30301393
TI  - T-lymphoblastic lymphoma after previous thymoma: how NGS helps establishing the
      diagnosis and procures new insights.

PMID- 30301394
TI  - What makes playgroups therapeutic? A scoping review to identify the active
      ingredients of therapeutic and supported playgroups.
AB  - BACKGROUND: Supported and therapeutic playgroups aim to support and strengthen
      vulnerable children and families by increasing parenting capacity, parent-child
      interaction, enhancing child outcomes and promoting community networks. This
      review aimed to comprehensively scope the literature to identify the "active
      ingredients" of supported and therapeutic playgroups. METHOD: A systematic search
      of grey and scholarly literature was conducted using Medline, PyschINFO, EMBASE,
      ERIC, CINAHL, MedNar, Informit, Scopus, Libraries of Australia and Trove.
      Articles were included if they: i) defined playgroup as a group of children and
      actively involved caregivers; ii) described a therapeutic playgroup or supported
      playgroup model; iii) targeted children prior to school age; and iv) measured the
      impact of playgroups. A total of 36 articles met the inclusion criteria.
      Qualitative data was synthesised using a meta-ethnography approach with findings
      charted against a conceptual model of engagement. Quantitative data was
      synthesised using descriptive statistics. RESULTS: The findings identified that
      emotional, practical and informational components of playgroups strongly reflect
      family centred practice, self-efficacy theory and peer-support principles.
      CONCLUSION: Therapeutic and supported playgroups are complex interventions, with
      numerous interacting components that make them beneficial for children and
      families. This review is the first to identify the "active ingredients" of
      playgroups with findings informing the design of future playgroups for vulnerable
      children and families.

PMID- 30301395
TI  - Response to pembrolizumab and lenalidomide in advanced refractory mycosis
      fungoides.

PMID- 30301396
TI  - Expression of TLE1 in Malignant Melanoma With Spindle Cell Morphology: A
      Potential Diagnostic Pitfall.
AB  - OBJECTIVES: Transducer-like enhancer of split 1 (TLE1) immunohistochemistry is
      widely used as a biomarker of synovial sarcoma. Spindle cell or desmoplastic
      melanoma can morphologically mimic synovial sarcoma. The aim of this study was to
      investigate the expression of TLE1 in melanomas with a spindle cell morphology.
      METHODS: A search of the surgical pathology files resulted in 57 cases of
      melanomas diagnosed with a spindle cell or desmoplastic component. After review,
      8 cases had no definitive dermal spindle cell component and 7 cases had
      insufficient tissue remaining and were excluded from the study. A total of 42
      melanomas were examined for TLE1 immunohistochemistry using a mouse monoclonal
      antibody (Cell Marque, clone 1F5). Strength and percentage of nuclear TLE1
      positivity was graded on a scale from 0 to 3+. Staining for TLE1 was considered
      positive for 2 to 3+ and negative for 0 to 1+. RESULTS: Nuclear TLE1 expression
      was identified in 24 (57%) of the 42 melanoma cases with spindle cell morphology
      (2+, n = 14; 3+, n = 10). TLE1 was considered negative in 18 cases (43%), of
      which most contained weak staining (1+, n = 14 [33%]) and only a small subset did
      not show any staining (0, n = 4 [10%]). CONCLUSION: TLE1 frequently highlights
      melanomas with spindle cell morphology and is a potential diagnostic pitfall.
      Therefore, when evaluating spindle cell tumors in which the differential may
      include both a melanoma and synovial sarcoma, TLE1 expression should be
      interpreted with caution and in conjunction with an immunohistochemical panel.

PMID- 30301397
TI  - Everyday activities outside the home are a struggle: Narratives from two persons
      with acquired brain injury.
AB  - BACKGROUND: Participation restriction is a common consequence after acquired
      brain injury (ABI). AIM: To explore and identify problematic situations in
      everyday activities outside the home for persons with acquired brain injury.
      MATERIAL AND METHOD: Two persons of working age with ABI were included. Data were
      generated through repeated semi-structured interviews and participant
      observations. Narrative analysis was used to capture ongoing processes related to
      problematic situations during engagement in everyday activities outside the home.
      RESULTS: The narratives reflect how places, everyday activities and social
      relations were closely connected and influenced engagement in everyday activities
      outside the home. The participants visited fewer places and performed more of
      their everyday activities alone in their homes after the injury compared to
      before. They were struggling to create meaning in their lives and trying to
      reformulate their identity. Problematic situations often occurred outside the
      home as a result of unexpected events. The narratives indicate a struggle to find
      new routines to handle challenging situations. CONCLUSIONS: The results provide
      an understanding of how problematic situations occurred and were managed in
      different ways. By observing everyday situations professionals can gain access to
      how persons with ABI act in and reflect upon problematic situations which can
      eventually improve the design of individually tailored interventions.

PMID- 30301398
TI  - Re-examining insulin compared to non-insulin therapies for type 2 diabetes: when
      in the disease trajectory is insulin preferable?
AB  - In patients with type 2 diabetes secondary to excess nutrients and energy
      balance, relative - not absolute - insulin deficiency plays a key role in disease
      development and progression. Although patients with type 2 diabetes who have
      features of insulin resistance would usually have hyperinsulinemia, insulin
      therapy remains recommended by guidelines particularly when patients fail to
      achieve glycemic goals. This approach does not prevent complications particularly
      macrovascular complications. This raises a controversial question regarding the
      benefit of using exogenous insulin for glycemic control in patients with type 2
      diabetes who have features of insulin resistance. To address this concern, the
      authors performed a literature search looking for either randomized trials or
      meta-analyses directly comparing exogenous insulin to non-insulin therapy in the
      treatment of patients with type 2 diabetes. Our main outcomes of interest were
      effect on glycemic control and insulin resistance at various time points in the
      usual trajectory of type 2 diabetes. In trials investigating early short-term
      initiation of intensive insulin therapy, insulin therapy was beneficial in
      rapidly achieving glycemic control and reversing glucotoxicity. Following the
      initial 2 weeks to 3 months of adequate glycemic control in patients on intensive
      insulin therapy, there is little evidence that continuing insulin therapy
      provides greater glycemic control or improves insulin resistance beyond what can
      be achieved with other therapies. In conclusion, long-term insulin use appears
      neutral if not potentially harmful with respect to insulin resistance and
      cardiovascular outcomes. While this review has limitations and should be dealt
      cautiously, it raises questions regarding the benefit of insulin in patients with
      type 2 diabetes with features of insulin resistance. Further research is needed
      to confirm these findings.

PMID- 30301400
TI  - Undergraduate anesthetic education: Medical students' perspectives.

PMID- 30301399
TI  - Clinical and biological characteristics of acute myeloid leukemia with 20-29%
      blasts: a retrospective single-center study.
AB  - It is controversial whether acute myeloid leukemia (AML) patients with 20-29%
      bone marrow (BM) blasts should be considered AML or myelodysplastic syndromes
      (MDS). We retrospectively studied 382 patients, including 108 AML with 20-29% BM
      blasts (AML20-29), 210 AML with >=30% BM blasts (AML >= 30), and 64 MDS with 10
      19% BM blasts (MDS-EB2). We found that AML20-29 were more similar to MDS-EB2 in
      terms of advanced age, less blood count, the increased presence of poor-risk
      cytogenetics. The frequency of mutated genes in AML20-29 had both the characters
      of AML and MDS. Median overall survival of AML20-29 and MDS-EB2 were similar and
      shorter than those of AML >= 30 (p = .045). Multivariate analysis showed inferior
      survival with increased age, low platelet count and FLT3 mutations. Our findings
      suggest that AML20-29 have clinical features more similar to MDS than AML.

PMID- 30301401
TI  - Autophagy determines mtDNA copy number dynamics during starvation.
AB  - Derived from bacterial ancestors, mitochondria have maintained their own albeit
      strongly reduced genome, mitochondrial DNA (mtDNA), which encodes for a small and
      highly specialized set of genes. MtDNA exists in tens to thousands of copies
      packaged in numerous nucleoprotein complexes, termed nucleoids, distributed
      throughout the dynamic mitochondrial network. Our understanding of the mechanisms
      of how cells regulate the copy number of mitochondrial genomes has been limited.
      Here, we summarize and discuss our recent findings that Mip1/POLG (mitochondrial
      DNA polymerase gamma) critically controls mtDNA copy number by operating in 2
      opposing modes, synthesis and, unexpectedly, degradation of mtDNA, when yeast
      cells face nutrient starvation. The balance of the 2 modes of Mip1/POLG and thus
      mtDNA copy number dynamics depends on the integrity of macroautophagy/autophagy,
      which sustains continuous synthesis and maintenance of mtDNA. In autophagy
      deficient cells, a combination of nucleotide insufficiency and elevated
      mitochondrial ROS production impairs mtDNA synthesis and drives mtDNA degradation
      by the 3'-5'-exonuclease activity of Mip1/POLG resulting in mitochondrial genome
      depletion and irreversible respiratory deficiency. Abbrivations: mtDNA:
      mitochondrial DNA; mtDCN: mitochondrial DNA copy number.

PMID- 30301402
TI  - Viewpoints on how students with autism can best navigate university.
AB  - BACKGROUND: Despite recognition of the challenges faced by students with autism
      spectrum disorders (ASD) there is limited understanding of the barriers and
      facilitators to participation in major life areas, such as being a university
      student. AIM/OBJECTIVE: This research aimed to examine viewpoints on what affects
      the success of Australian university students with ASD. MATERIAL AND METHOD: Q
      methodology was used to describe the viewpoints of university students with ASD,
      their parents and their mentors, on success at university for students with ASD.
      A total of 57 participants completed the Q-sort. RESULTS/FINDINGS: Three
      viewpoints emerged; Individualised Support, Contextual Support and Social
      Support. CONCLUSIONS: This study highlighted that supports need to be
      individualized to the barriers and facilitators faced by Australian students with
      ASD. Supports also need to be contextualized to the built and social environments
      of universities. SIGNIFICANCE: This study supports the premise that environmental
      interventions can be effective in facilitating participation in major life areas,
      such as university education. Peer mentoring for students with ASD may have
      utility for this group, but should be extended to include social, emotional and
      psychological support.

PMID- 30301403
TI  - ASXL1 is a molecular predictor in idiopathic cytopenia of undetermined
      significance.
AB  - We analyzed the mutational profile of idiopathic cytopenia of undetermined
      significance (ICUS) compared with that of myelodysplastic syndrome (MDS).
      Targeted sequencing of 88 genes associated with myeloid malignancies was
      performed using samples of bone marrow mononuclear cells from ICUS and MDS
      patients. Forty patients with ICUS and 128 patients with MDS were included in
      this study. The median mutational burden was 0.7 mutation/person in the ICUS
      group and 2.2 mutation/person in the MDS group. ASXL1 (seven patients) was the
      most frequently mutated gene. ASXL1 was an independent significant prognostic
      factor for event-free survival (EFS) and overall survival (OS) (hazard ratio (HR)
      = 10.07 and 30.63, p = .004 and .003, respectively). The ASXL1 mutation which is
      frequently detected in elderly patients is a molecular predictor for pancytopenia
      and survival in patients with ICUS. A larger prospective study is needed to
      validate the role of this genetic mutation in an ICUS prognosis.

PMID- 30301406
TI  - Phase I and phase II metabolism simulation of antitumor-active 2
      hydroxyacridinone with electrochemistry coupled on-line with mass spectrometry.
AB  - 1. Here, we report the metabolic profile and the results of associated metabolic
      studies of 2-hydroxyacridinone (2-OH-AC), the reference compound for antitumor
      active imidazo- and triazoloacridinones. 2. Electrochemistry coupled with mass
      spectrometry was applied to simulate the general oxidative metabolism of 2-OH-AC
      for the first time. The reactivity of 2-OH-AC products to biomolecules was also
      examined. The usefulness of the electrochemistry for studying the reactive drug
      metabolite trapping (conjugation reactions) was evaluated by the comparison with
      conventional electrochemical (controlled-potential electrolysis) and enzymatic
      (microsomal incubation) approaches. 3. 2-OH-AC oxidation products were generated
      in an electrochemical thin-layer cell. Their tentative structures were assigned
      based on tandem mass spectrometry in combination with accurate mass measurements.
      Moreover, the electrochemical conversion of 2-OH-AC in the presence of reduced
      glutathione and/or N-acetylcysteine unveiled the formation of reactive metabolite
      nucleophilic trapping agent conjugates (m/z 517 and m/z 373, respectively) via
      the thiol group. This glutathione S-conjugate was also identified after
      electrolysis experiment as well as was detected in liver microsomes. 4. Summing
      up, the present work illustrates that the electrochemical simulation of metabolic
      reactions successfully supports the results of classical electrochemical and
      enzymatic studies. Therefore, it can be a useful tool for synthesis of drug
      metabolites, including reactive metabolites.

PMID- 30301405
TI  - Associations of Sedentary Behavior and Abdominal Muscle Density: The Multi-Ethnic
      Study of Atherosclerosis.
AB  - BACKGROUND: Sedentary behaviors (SB) may exacerbate loss of muscle mass and
      function, independent of physical activity levels. This study examined the
      associations of SB with abdominal muscle area and density, a marker of muscle
      quality, in adults. METHODS: A total of 1895 participants from the Multi-Ethnic
      Study of Atherosclerosis completed detailed health history, physical activity and
      SB questionnaires, computed tomography to quantify body composition, and
      measurements of inflammatory markers. Analyses included linear and nonlinear
      regression. RESULTS: The mean age and body mass index were 64.6 years and 28 kg.m
      2, respectively, and 50% were women. On average, participants engaged in 28
      metabolic equivalent hours.week-1 of SB. With adjustment for age, sex,
      race/ethnicity, physical activity, cardiovascular disease risk factors, and
      inflammation, multivariable regression modeling revealed a nonlinear (quadratic)
      relationship between SB and locomotor, stability, and total abdominal muscle
      density (P < .01) but not muscle area. The SB inflection point at which
      locomotor, stability, and total abdominal muscle density began to decrease was
      38.2, 39.6, and 39.2 metabolic equivalent hours.week-1 of SB, respectively.
      CONCLUSIONS: SB is associated with reduced muscle density when practiced as
      little as 5.5 metabolic equivalent hours.day-1. These findings may have important
      implications for SB guidelines for targeting skeletal muscle health in older
      adults.

PMID- 30301407
TI  - Ultrashort-Segment Embolization of High-Flow Vessels Using a Coil Packing
      Technique in an Amplatzer Vascular Plug.
AB  - PURPOSE: To report an experimental study and clinical case using a coil packing
      technique that hastens occlusion of an Amplatzer Vascular Plug 1 (AVP1) in short
      segment embolization of high-flow target vessels. TECHNIQUE: An experimental
      vascular stenosis model was made of 12-mm soft polyvinyl chloride tubing. Under
      continuous pulsatile flow, a 12-mm AVP1 was deployed in the 4-mm-diameter
      stenosis. Before detachment of the AVP1, a 2.2-F microcatheter was inserted into
      the AVP1 through its mesh via a 6-F delivery guiding sheath in parallel with the
      delivery wire. Hydrogel microcoils were deployed tightly in the AVP1 and the plug
      was detached. After the procedure, the pulsatile saline flow was nearly
      obliterated. In the first clinical case, a 64-year-old man with a thoracic aortic
      stent-graft and single vessel debranching for type B aortic dissection developed
      a residual type II endoleak via the left subclavian artery. This coil packing
      technique in an AVP1 was employed to successfully embolize the leak. CONCLUSION:
      Based on the experimental study and the first experience in vivo, tight coil
      packing of an AVP1 might be a robust technique for ultrashort-segment
      embolization.

PMID- 30301404
TI  - Potassium channels in the sinoatrial node and their role in heart rate control.
AB  - Potassium currents determine the resting membrane potential and govern
      repolarisation in cardiac myocytes. Here, we review the various currents in the
      sinoatrial node focussing on their molecular and cellular properties and their
      role in pacemaking and heart rate control. We also describe how our recent
      finding of a novel ATP-sensitive potassium channel population in these cells fits
      into this picture.

PMID- 30301408
TI  - The effect of hydraulic retention time on ammonia and nitrate bio-removal over
      nitrite process.
AB  - Ammonia and Nitrate Bio-removal Over Nitrite (ANBON) is a new biological process,
      which couples denitratation with Anaerobic Ammonium Oxidation (ANAMMOX) to carry
      out simultaneous removal of nitrate nitrogen and ammonia nitrogen. The effect of
      hydraulic retention time (HRT) on the performance of ANBON process was
      investigated. The results showed that the optimal HRT was about 0.7 h and the
      nitrogen removal rate was 26.2 +/- 0.7 g N.L-1.d-1, which was at top level
      reported in previous literatures. The change of HRT was found to trigger the
      change of microbial community in the reactor, which exerted a great effect on the
      performance of ANBON process. The community analysis based on 16S rRNA gene
      indicated that Halomonas and Candidatus Kuenenia were the dominant functional
      bacteria in the denitratation unit and the ANAMMOX unit respectively. These
      results are helpful for the development and application of ANBON process.

PMID- 30301409
TI  - Implementation and evaluation of Stanford Health Care store-and-forward
      teledermatology consultation workflow built within an existing electronic health
      record system.
AB  - Introduction Teledermatology services that function separately from patients'
      primary electronic health record (EHR) can lead to fragmented care, poor provider
      communication, privacy concerns and billing challenges. This study addresses
      these challenges by developing PhotoCareMD, a store-and-forward (SAF)
      teledermatology consultation workflow built entirely within an existing Epic
      based EHR. Methods Thirty-six primary care physicians (PCPs) from eight
      outpatient clinics submitted 215 electronic consults (eConsults) for 211 patients
      to a Stanford Health Care dermatologist via PhotoCareMD. Comparisons were made
      with in-person referrals for this same dermatologist prior to initiation of
      PhotoCareMD. Results Compared to traditional in-person dermatology clinic visits,
      eConsults decreased the time to diagnosis and treatment from 23 days to 16 hours.
      The majority (73%) of eConsults were resolved electronically. In-person referrals
      from PhotoCareMD (27%) had a 50% lower cancellation rate compared with
      traditional referrals (11% versus 22%). The average in-person visit and
      documentation was 25 minutes compared with 8 minutes for an eConsult. PhotoCareMD
      saved 13 additional clinic hours to be made available to the dermatologist over
      the course of the pilot. At four patients per hour, this opens 52 dermatology
      clinic slots. Over 96% of patients had a favourable experience and 95% felt this
      service saved them time. Among PCPs, 100% would recommend PhotoCareMD to their
      colleagues and 95% said PhotoCareMD was a helpful educational tool. Discussion An
      internal SAF teledermatology workflow can be effectively implemented to increase
      access to and quality of dermatologic care. Our workflow can serve as a
      successful model for other hospitals and specialties.

PMID- 30301410
TI  - Organic micropollutants in sewage sludge: influence of thermal and ultrasound
      hydrolysis processes prior to anaerobic stabilization.
AB  - Organic micropollutants (OMP) in the household and industrial wastewater are not
      efficiently removed by conventional treatment processes and a significant
      fraction ends in sludge. Proper valorization technologies become fundamental to
      attain sustainable sewage sludge management, with anaerobic digestion (AD) as one
      of the preferred strategies. However, it exhibits some limitations that can be
      overcome with pre-treatment processes. In this study, the influence of different
      pre-treatment configurations over OMP concentration and removal during AD was
      assessed. The incorporation of a sequential US - TT-PT resulted in decreased
      concentrations of 7 of the 9 detected compounds in biosolids compared to
      conventional AD digestate, with bisphenol-A and ter-octylphenol showing the
      opposite effect. The results suggest that the assessed PT could improve the
      removal of sequestered or highly hydrophobic compounds through their
      solubilization and increased bioavailability.

PMID- 30301412
TI  - Caregiver ratings and performance-based indices of executive function among
      preschoolers with and without maltreatment experience.
AB  - Despite the well-documented impact of early maltreatment on children's executive
      function (EF), there has been limited consensus about how to best assess this
      neurocognitive domain in high-risk, vulnerable preschool-aged children. Relevant
      studies have generally utilized either performance-based tests or caregiver
      ratings of EF, yet multi-method research has been rare. This study examined the
      EF profiles of preschoolers exposed to maltreatment, as indexed by the Behavior
      Rating Inventory of Executive function - Preschool Version (BRIEF-P), and
      investigated associations between caregiver ratings and performance-based
      measures (Happy-Sad Stroop, Tapping Test, and Dimensional Change Card Sort -
      DCCS) of EF in this population. Maltreatment status was further tested as a
      moderator of associations between these measures. Participants were (n = 107)
      children aged 4-5 years (M = 4.75; SD = 0.57; 39% female), with various levels of
      exposure to maltreatment. Children exposed to maltreatment were found to exhibit
      significantly more caregiver-rated deficits in EF than non-maltreated children,
      with greater fluctuations apparent across all scales of the BRIEF-P. Consistent
      with previous research in neurologically impaired children, there were only
      limited and weak to moderate correlations between BRIEF-P scales and performance
      based measures of EF. Furthermore, maltreatment status was found to moderate the
      association between scores on the BRIEF-P Inhibit Scale and the DCCS, such that
      the association between these indices was weaker among children exposed to higher
      levels of maltreatment.

PMID- 30301411
TI  - An overview about the impact of Hinge Region towards the Anticancer Binding
      Affinity of the Ck2 Ligands- A Quantum Chemical Analysis.
AB  - Casein Kinase 2 (CK2) is extremely preserved and universally uttered
      serine/threonine kinase, vital for cellular feasibility. The present study was
      aimed to analyse the binding strength of CK2 ligands specifically in the hinge
      region, as it is aware that most of the existing drugs are targeted to bind the
      hinge of the corresponding protein. The analysis will give a clear picture about
      the role of hinge region with ligand, which will be useful for scientist
      community in drug designing. To predict the binding strength of CK2 ligands, the
      role of halogen bond, hydrogen bond interaction at the hinge region was depicted
      in detail through interaction energy calculations at M062Z/def2-QZVP level of
      theory. HOMO map plotted for CK2 ligands gives clear pictorial representation of
      orbital's, which induce for interaction. Ligand properties discussed in detail
      through Lipinski's five rules predict that almost all the ligands satisfy the
      rule, except 3KXG, which violates the Lipinski's two rules i.e molecular mass
      exceeds 500 Da i.e. 512.61 Da and log P value is high of 5.09. The natural bond
      orbital analysis deliberate that the hydrogen/halogen bonds figuring out within
      the complexes are observed to have moderate stabilization energy, but those
      hydrogen/halogen bonds that exist with close contacts have high stabilization
      energy. Overall this computational work will give an understandable depiction for
      modelling anticancer ligands along the hinge region in CK2 protein; also it will
      give a new path for the choice of side chains on the ligand.

PMID- 30301413
TI  - Changes in Smoking During Retirement Transition: A Longitudinal Cohort Study.
AB  - AIMS: We examined the effect of retirement transition on changes in smoking,
      identified trajectories of smoking around the retirement transition, and
      investigated factors predicting the membership in the trajectories. METHODS: This
      longitudinal cohort study included 1,432 current or former smokers who entered
      into statutory retirement in 2000-2011 and who filled out two to four
      questionnaires sent at four-year intervals. Effect of retirement on smoking was
      analysed as a non-randomized pseudo-trial in which we compared the likelihood of
      quitting and relapsing smoking between two subsequent survey waves among those
      who retired and did not retire. We used latent class analysis to identify
      trajectories of smoking status and smoking intensity (low: <10 cigarettes/day or
      high: ?10 cigarettes/day), and multinomial logistic regression models to assess
      pre-retirement factors associated with smoking trajectories. RESULTS: Retirement
      transition was associated with 1.7-fold odds of quitting smoking (95% confidence
      intervals 1.3-2.2) compared with no retirement transition. We identified three
      smoking status trajectories: 'sustained non-smoking' (61% of the participants),
      'sustained smoking' (23%) and 'decreasing smoking' (16%). For 489 baseline
      smokers, we identified three smoking intensity trajectories: 'sustained high
      intensity smoking' (32% of the participants), 'sustained low intensity smoking'
      (32%) and 'decreasing high intensity smoking' (35%). Living outside an inner
      urban area predicted membership in the 'decreasing smoking' versus 'sustained
      smoking' trajectory. CONCLUSIONS: Smokers are more likely to quit smoking during
      transition to retirement than before or after it. Characteristics of the smoking
      environment may affect smoking behaviour around retirement.

PMID- 30301414
TI  - A phase I study of romidepsin, gemcitabine, dexamethasone and cisplatin
      combination therapy in the treatment of peripheral T-cell and diffuse large B
      cell lymphoma; the Canadian cancer trials group LY.15 study?.
AB  - We investigated GDP (gemcitabine, 1000 mg/m2 IV d1, d8; dexamethasone, 40 mg po
      d1-4; cisplatin, 75 mg/m2 IV d1) combined with romidepsin on days 1 and 8 every
      21 days to a maximum of six cycles in a standard 3 + 3, phase I dose escalation
      trial for patients with relapsed/refractory peripheral T-cell (PTCL) or diffuse
      large B-cell (DLBCL) lymphoma (NCT01846390). After treating four patients,
      gemcitabine and romidepsin were given on days 1 and 15 every 28 days. On the 21
      day schedule at 6 mg/m2 romidepsin, there were three dose-limiting toxicities
      (DLTs) among four patients. On the 28-day schedule, there were no DLTs at the 6,
      8, or 10 mg/m2 dose. At 12 mg/m2, there were four observed grade 3 DLTs among six
      evaluable patients. Full doses of GDP can be combined with a recommended phase II
      romidepsin dose of 10 mg/m2 if given on a day 1, 15 every 28 days schedule.

PMID- 30301415
TI  - Examining the relationship between performance-based and questionnaire
      assessments of executive function in young preterm children: Implications for
      clinical practice.
AB  - The aim of this study was to determine whether specific performance-based
      executive function assessment tools were associated with executive functioning in
      everyday life as reported by parents and teachers of four- to five-year-old
      preterm and term children. At the age of 4 years, 141 preterm children born <33
      weeks' gestation and 77 term children were assessed using performance-based
      intelligence (WPPSI-III) and executive function (EF) assessment tools (NEPSY-II,
      Day-Night and Shape School tasks). The assessment results were compared with the
      parent and teacher completed questionnaires of EF (BRIEF-P) when the children
      started kindergarten at the age of 4 to 5 years. The performance-based
      intelligence and EF assessment results were not consistently associated with the
      parent and teacher reports of EF in everyday life for either preterm or term
      groups. Clinical implications of using and interpreting performance-based EF
      assessment tools and EF questionnaires are discussed with a particular focus on
      young preterm children at the commencement of formal schooling.

PMID- 30301416
TI  - The lived experience of people with intellectual disabilities in post-secondary
      or higher education.
AB  - The transformational role education plays in the lives of people with
      intellectual disabilities has not been fully examined. The purpose of this study
      was to explore and investigate the meanings people with intellectual disabilities
      construct of their experiences in post-secondary and higher education.
      Heideggerian hermeneutic phenomenology was the qualitative methodology adopted
      for the study. Individual interviews were conducted with 27 people with
      intellectual disabilities and analysed in stages. These stages included the
      creation of I-Poems offering a unique opportunity for individual participant
      voices to be heard. Three core themes emerged to describe living an authentic
      life: learning (with the emphasis on increased skills, independence and
      opportunities); relationships (in particular, the importance of friendships), and
      perceptions including the existing realities of life for those with intellectual
      disabilities. The findings advance previous work highlighting the link between
      living a more authentic life and how education transforms how people with
      intellectual disabilities view themselves.

PMID- 30301418
TI  - ECTRIMS 2018 Committees.

PMID- 30301420
TI  - Visual Impairment Was Related to Educational Level but Not to Cognitive
      Performance Among Adults in Their 60s.
AB  - Background Older people are at greater risk of both physical impairments and
      cognitive decline. Although previous studies have examined whether visual and
      cognitive impairments are associated, findings have been mixed with cognitive
      performance only crudely assessed. Nonetheless, it remains possible that this
      association becomes stronger with age. Accordingly, in the present study, we
      tested the hypothesis that older people with visual impairments have poorer
      cognitive performance than healthy controls. To this end, we employed validated
      tools to assess both visual-related and visual-unrelated cognitive skills.
      Methods A total of 30 older adults (mean age: M = 63.98 years, 30% females) with
      poor vision (logMAR value 1.0 or higher) and 30 gender- and age-matched healthy
      controls with no visual impairments (logMAR value 0.2 or lower) took part in this
      cross-sectional study. After a careful medical and psychiatric examination,
      participants underwent thorough cognitive testing for working and long-term
      memory and attention. Results Cognitive performance did not differ between those
      with and without visual impairments, though better cognitive performance scores
      were associated with higher educational level. Conclusions Among older people,
      visual impairment was unrelated to cognitive performance. Rather, cognitive
      function was related to level of education.

PMID- 30301421
TI  - Relationship Between Autism Spectrum Disorder Characteristics and Humor
      Appreciation in Typically Developing Individuals.
AB  - Extant research regarding humor appreciation in individuals with autism spectrum
      disorder has been equivocal. This study aims to clarify the relationship between
      the severity of autism spectrum disorder characteristics and humor appreciation
      in typically developing individuals. We hypothesized that the severity of
      autistic traits would have a U-shaped linear relationship with humor
      appreciation. Eighty typically developing undergraduates between the ages of 18
      and 22 years ( Mage = 20.20; SDage = 1.08) were recruited for this study. They
      were asked to answer 24 statements, devised to measure humor appreciation, in
      response to a joke stimulus comprising 12 typically funny daily life occurrences
      (two statements per episode). The participants also responded to the Japanese
      version of the Autism-Spectrum Quotient. A significant U-shaped relationship was
      observed between the severity of autistic traits and appreciation of humor. A
      similar significant U-shaped relationship was seen between humor appreciation and
      the Autism-Spectrum Quotient subscales of attention switching, communication, and
      imagination. Humor appreciation showed no significant U-shaped relationship with
      the Autism-Spectrum Quotient subscales of social skills and local details. This
      study identified ways that autistic traits may influence how people appreciate
      humor. These findings are discussed in relation to cognitive processes underlying
      humor appreciation.

PMID- 30301422
TI  - The role of social embeddedness for remaining in non-desired workplaces and
      mental health consequences: Results from Scania Public Health Cohort.
AB  - AIMS: The aim of the study was to investigate the role of social embeddedness on
      and off the job in relation to remaining in non-desired workplaces (NDWs) and the
      development of mental health. METHOD: The study used questionnaire data from the
      Scania Public Health cohort ( N=2410) that were collected in 2000 (T1), 2005 (T2)
      and 2010 (T3). Logistic regression models were calculated to probe how NDWs and
      social embeddedness factors measured at baseline (T1) related to NDWs five years
      later (T2), and to investigate how NDWs and social embeddedness factors at T2
      related to poor mental health at T3. Synergy indices were calculated in both
      analyses to test for additive v. interactive effects between NDWs and social
      embeddedness factors on the outcomes. RESULTS: NDWs at baseline and low social
      embeddedness on and off the job was associated with NDWs at T2. For those in a
      desired workplace, low support from co-workers as well as low workplace affinity
      increased the risk to be in an NDW at T2. NDWs and low social embeddedness also
      associated with impaired mental health (T3). For those in an NDW, low support
      from co-workers as well as low workplace affinity increased the risk of poor
      mental health at T3. CONCLUSIONS: This study underlines the importance of social
      embeddedness for NDWs and the development of poor mental health over time.
      Particularly low social support from co-workers and low workplace affinity seem
      to be risk factors for future experience of an NDW and impaired mental health.

PMID- 30301423
TI  - Investigation of activation mechanism and conformational stability of N-(4-chloro
      3-trifluoromethyl-phenyl)-2-ethoxybenzamide and N-(4-chloro-3-trifluoromethyl
      phenyl)-2-ethoxy-6-pentadecyl-benzamidein the active site of p300 histone acetyl
      transferase enzyme by molecular dynamics and binding free-energy studies.
AB  - The CBP (CREB binding protein) and p300 are related to transcriptional
      coactivator family and are involves several post translational modifications; in
      which the acetylation is an important factor because it commences the
      transcription process. Experimental studies report that CTPB [N-(4-chloro-3
      trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide] and CTB [N-(4-chloro-3
      trifluoromethyl-phenyl)-2-ethoxybenzamide] are good activators of p300 HAT
      enzyme, but yet the molecular mechanism of their activation is not explored. The
      present study pertains to determine the intermolecular interactions, stability
      and binding free energy of CTB and CTPB from the molecular docking, molecular
      dynamics (MD) simulation and binding free energy calculation. The docking studies
      of the molecules reveal that the docking score of CTPB (-15.64 kcal/mol) is
      higher than CTB (-12.30 kcal/mol); contrary, CTB forms strong interaction with
      the key residues of catalytic site (Tyr1467, Trp1436) compare with CTPB. The MD
      simulation shows the stability of both molecules in the active site of p300 and
      their interactions. Furthermore, both docking and MD simulation studies of CTB
      confirm that it forms expected key interactions and retain the interactions with
      the active site amino acid residues of p300 on compared with CTPB. For this
      reason, the CTB recruits more acetyl-CoA in the active site of p300 compared with
      CTPB; it leads to activate the acetylation process, hence, CTB may be a best
      activator than CTPB. The binding free energy value of CTPB (-24.79+/-2.38
      kcal/mol) is high on compare with CTB (-12.14+/-1.30 kcal/mol) molecule; perhaps
      the interaction of pentadecyl chain of CTPB with p300, whereas in CTB such group
      is absent.

PMID- 30301424
TI  - The Rationality of (Over)imitation.
AB  - Imitation is a powerful and ubiquitous social learning strategy, fundamental for
      the development of individual skills and cultural traditions. Recent research on
      the cognitive foundations and development of imitation, though, presents a
      surprising picture: Although even infants imitate in selective, efficient, and
      rational ways, children and adults engage in overimitation. Rather than imitating
      selectively and efficiently, they sometimes faithfully reproduce causally
      irrelevant actions as much as relevant ones. In this article, we suggest a new
      perspective on this phenomenon by integrating established findings on children's
      more general capacities for rational action parsing with newer findings on
      overimitation. We suggest that overimitation is a consequence of children's
      growing capacities to understand causal and social constraints in relation to
      goals and that it rests on the human capacity to represent observed actions
      simultaneously on different levels of goal hierarchies.

PMID- 30301425
TI  - Workplace inclusion of employees with back pain and mental health problems: A
      focus group study about employees' experiences.
AB  - AIM: To explore how employees experience workplace inclusion of their colleagues
      or themselves when having back pain or mental health problems. METHODS: Three
      focus group interviews with a sample of 16 kindergarten employees were conducted.
      Systematic Text Condensation was used for analysis. RESULTS: The participants
      emphasized that it was easier to include colleagues whose health problems were
      specific, especially when they were open about having problems and expressed
      their needs for accommodation clearly. Discussions revealed difficulties of
      acceptance and accommodating colleagues with longstanding health problems, when
      the burden on the other staff members was heavy, and if it had negative
      consequences for the kindergarten children. Some of the participants had
      experienced health problems themselves, which was also described as challenging.
      Having health problems at work often induced feelings of guilt, being a burden to
      their colleagues, and experiencing a disparity between the ideals and the
      realities of inclusion practices. CONCLUSIONS: Workplace inclusion of employees
      is difficult when their health problems are unspecific, longstanding, and lead to
      negative consequences for children or colleagues. System level efforts are
      necessary to reduce negative stereotypes about employees with health problems and
      facilitate inclusion practices.

PMID- 30301426
TI  - Discomfort discussing HIV/AIDS and lack of awareness are barriers to partner-to
      partner pre-exposure prophylaxis education.
AB  - We suggest that people living with HIV (PLWH) may serve as pre-exposure
      prophylaxis (PrEP) educators for partners when informed about PrEP. Participants
      in this study were a convenience sample of PLWH at a public hospital in Miami. A
      cross-sectional survey assessed the frequency of serostatus disclosure, PrEP
      awareness, and willingness to recommend PrEP to intimate partners. To evaluate
      stigma surrounding human immunodeficiency virus (HIV), comfort discussing HIV
      with family, friends and intimate partners was interrogated. Surveys were
      completed by 137 participants; 39.5% had potentially sero-discordant sexual
      partners. Among respondents, 29.2% reported that they 'occasionally' or 'never'
      disclose HIV status to sexual partners. In all, 66.4% of patients reported that
      they had never heard of PrEP. After being educated about PrEP, 86.0% of
      respondents reported that they would encourage partners to use it. Participants
      were asked how often the subject of HIV comes up in conversations. Most indicated
      that 'rarely' or 'never' does it come up with friends and family; 46.1% indicated
      that 'never' or 'rarely' does it come up with partners. In bivariate analyses,
      participants with prior awareness of PrEP were more likely to indicate higher
      frequency of conversations regarding HIV with intimate partners. It is concluded
      that interventions which utilize partner education to increase PrEP uptake should
      address stigma and knowledge among other barriers.

PMID- 30301427
TI  - Blunted serum 25(OH)D response to vitamin D3 supplementation in children with
      autism.
AB  - INTRODUCTION: Data suggest a potential role for vitamin D in autism spectrum
      disorder (ASD) prevention and treatment. It is likely that the serum response to
      vitamin D supplementation contributes to its effectiveness. Multiple factors
      affect serum vitamin D 25(OH)D response to supplementation. METHODS: We conducted
      post-hoc analysis of two double-blind, randomized, placebo-controlled trials
      (RCT) of vitamin D3 supplementation, one RCT involving children with ASD and
      another involving children with asthma. Both trials were conducted in the same
      geographic location (Dublin, Ireland, 53 degrees N), conducted over Winter season
      and utilized the same vitamin D3 dose (2000 IU/day). RESULTS: We included 18
      children with ASD and 17 children with asthma. There was no significant
      difference in 25(OH)D or age at baseline, however, BMI was significantly lower in
      ASD (P = 0.03). Compliance with vitamin D supplementation was high in both
      trials. Despite a significantly longer intervention period (20w vs. 15w; P <
      0.0001), ASD children had a significantly lower absolute increase (+26 vs. +45
      nmol/l) in 25(OH)D (P = 0.04). CONCLUSIONS: Despite similar demographics,
      children with ASD had a lower increase in 25(OH)D levels with supplementation.
      Potential mechanisms include altered absorption/metabolism as well as well
      genetic factors. Clinical and research work relating to vitamin D is ASD should
      measure 25(OHO)D response to supplementation to assess therapeutic doses.

PMID- 30301428
TI  - On the Margins of Death: A Scoping Review on Palliative Care and Schizophrenia.
AB  - Schizophrenia is a serious chronic mental illness that results in marginalization
      and stigma for sufferers. It is the seventh leading cause for disability
      worldwide. The symptoms of the illness, including hallucinations, delusions, and
      extremely disordered thinking and behavior, may also introduce barriers to
      accessing treatment, education, housing, and employment. Little is known about
      end-of-life care for individuals with schizophrenia. To address this gap, a
      scoping review was conducted to enhance understanding of hospice and palliative
      care for patients with schizophrenia. From this scoping review, 342 unique titles
      and abstracts were identified through a search of 20 databases, including 11
      social science databases, 6 medical databases, and 3 gray literature databases. A
      total of 32 articles met the inclusion criteria and the following 4 themes were
      identified: Stigma affecting quality of care and access to care; Issues related
      to consent and capacity for the patient's end-of-life care decisions and to
      appoint substitute decision makers; Best practices for psychosocial
      interventions, pharmacology, family and health-care collaborations, goals of
      care, setting, and smoking; and Barriers to care, including setting,
      communication, provider education, and access to care. The review suggests the
      importance of mandatory interdisciplinary training practices and policy standards
      outlining cooperative communication across health-care providers. It highlights
      gaps in evidence-based research on psychosocial interventions and collaborative
      frameworks to enable the provision of quality end-of-life care for individuals
      with schizophrenia.

PMID- 30301429
TI  - Utilizing bioaugmentation to improve performance of a two-phase AnMBR treating
      sewage sludge.
AB  - Bioaugmentation in the acid-phase of a two-phase anaerobic membrane bioreactor
      (AnMBR) treating primary sludge was investigated as a means for targeting and
      improving hydrolysis and acetogenesis. Bioaugmentation was carried out using a
      proprietary bioculture blend containing a mixture of hydrolytic, acidogenic, and
      acetogenic microorganisms. This mixture was added on its own and in combination
      with recycled anaerobic sludge from the methane-phase of the AnMBR. Both
      bioaugmentation strategies had a positive effect on overall hydrolysis (25-38%),
      and acid-phase acetic acid generation (31-52%) compared to operation without
      bioaugmentation. This led to subsequent increases in average methane production
      (10-13%), and greater average solids reduction (25-55%). Microbial community
      analysis using 16S Illumina MiSeq generated sequences revealed increased relative
      abundance of Acetobacter and Syntrophomonas species in bioaugmented communities,
      suggesting these to be key players in improvements in process performance.
      However, in general the relative abundance of bioaugmented microorganisms within
      bioaugmented communities was relatively low, highlighting the need to optimize
      the bioculture composition and dosage. Overall, bioaugmentation was found to
      benefit the conversion of primary sludge to methane, when initial solubility was
      relatively low. Future work should optimize the bioculture composition and dosing
      strategy to improve its effectiveness and long-term stability, and minimize
      associated operating costs.

PMID- 30301430
TI  - Acute Stroke Treatment by Surgical Recanalization of Extracranial Internal
      Carotid Artery Occlusion: A Single Center Experience.
AB  - Ischemic stroke due to an acute occlusion of the extracranial internal carotid
      artery (eICA) is associated with high morbidity and mortality. The best treatment
      option remains unclear. This study aims to increase the available therapeutic
      experience documented for surgical recanalization of acute eICA occlusions. We
      retrospectively reviewed all hospital records of the University Hospital Jena
      between 2006 and 2018 to identified patients with acute ischemic stroke due to an
      occlusion of the eICA who underwent emergent surgical recanalization. We analyzed
      clinical data, surgical reports, imaging data, and outpatient records. The
      primary outcome parameter was the modified Rankin Scale (mRS) at 3 months. During
      the survey, 12 patients (mean age: 62.3 +/- 10.8 years; range: 35-87) underwent
      emergent surgical recanalization for an acutely symptomatic eICA occlusion. All
      patients presented with neurological deficits with a mean National Institutes of
      Health Stroke Scale score at admission of 15.0 +/- 5.1 (range 2-23). Patients
      were selected for surgery mainly due to the extent of the perfusion mismatch,
      while stroke severity and age were also considered. The median time from symptom
      onset to surgery was 309 +/- 122 minutes (range 112-650 minutes). Complete
      recanalization was obtained in all 12 patients. No patient deteriorated
      postoperatively, no intracranial hemorrhage was observed, and no patient died in
      the following 3 months. Favorable outcomes (mRS: 0-2) after 3 months were
      achieved in 7 of 12 patients. The current study adds support to previous findings
      that the surgical recanalization of acute eICA occlusions is a possible and safe
      treatment option. However, a critical patient selection based on mismatch size in
      perfusion imaging is crucially important for successful treatment.

PMID- 30301431
TI  - Metal Coordinated Poly-Zinc-Liothyronine Provides Stable Circulating
      Triiodothyronine Levels in Hypothyroid Rats.
AB  - BACKGROUND: Liothyronine (LT3) has limited short-term clinical applications, all
      of which aim at suppressing thyrotropin (TSH) secretion. A more controversial
      application is chronic administration along with levothyroxine in the treatment
      of hypothyroidism. Long-term treatment with LT3 is complicated by its unique
      pharmacokinetics that result in a substantial triiodothyronine (T3) peak in the
      blood three to four hours after oral dosing. This is a significant problem, given
      that T3 levels in the blood are normally stable, varying by <10% throughout the
      day. METHODS: A metal coordinated form of LT3 (Zn[T3][H2O])n, known as poly-zinc
      liothyronine (PZL), was synthesized and loaded into coated gelatin capsules for
      delivery to the duodenum where sustained release of T3 from PZL occurs. Male
      Wistar rats were made hypothyroid by feeding on a low iodine diet and water
      containing 0.05% methimazole for five to six weeks. Rats were given a capsule
      containing 24 MUg/kg PZL or equimolar amounts of LT3. Blood samples were obtained
      multiple times from the tail vein during the first 16 hours, and processed for T3
      and TSH serum levels. Some animals were treated daily for eight days, and blood
      samples were collected daily. RESULTS: Rats given LT3 exhibited the expected
      serum T3 peak (about fivefold baseline) at 3.5 hours, followed by a rapid
      decline, with serum levels almost returning to baseline values by 16 hours. In
      contrast, serum T3 in PZL-treated rats exhibited about a 30% lower T3 peak at
      nine hours. Furthermore, the plateau time, that is, the time-span during which
      the serum T3 concentration is at least half of T3 peak, increased from 4.9 to 7.7
      hours in LT3- versus PZL-treated rats, respectively. Serum TSH dropped in both
      groups, but PZL-treated rats exhibited a more gradual decrease, which was delayed
      by about four hours compared to LT3-treated rats. Chronic treatment with either
      LT3 or PZL restored growth, lowered serum cholesterol, and stimulated hepatic
      expression of the Dio1 mRNA and other T3-dependent markers in the central nervous
      system. CONCLUSION: Capsules of PZL given orally restore T3-dependent biological
      effects while exhibiting a reduced and delayed serum T3 peak after dosing, thus
      providing a longer period of relatively stable serum T3 levels compared to
      capsules of LT3.

PMID- 30301432
TI  - Using Social Network Analysis to Identify Successful Relationship Patterns Within
      Sexual Assault Response Teams (SARTs).
AB  - The current study used social network analysis (SNA) to examine relationships
      within three effective Sexual Assault Response Teams (SARTs) that coordinate the
      response of legal, medical, and advocacy organizations to sexual assault. Within
      each SART, organizations reported on each other member organization valuing their
      role, serving as a resource to their work, and communication outside of official
      meetings. Across the SARTs, there was high connectedness and reciprocity and low
      to moderate dependence on one organization to drive relationships. However, there
      was dependence on a subgroup of organizations to drive additional communication
      relationships. Implications for managing relationships in SARTs are discussed.

PMID- 30301433
TI  - Endovascular Treatment of Simultaneous Iliac and Superficial Femoral Arterial
      Pseudoaneurysms After Stenting Procedure Complications.
AB  - PURPOSE: To report on the endovascular management of a patient affected by
      concomitant left common iliac artery and right superficial femoral artery (SFA)
      pseudoaneurysms after stent positioning. CASE REPORT: A 77-year-old man affected
      by severe lower limb atherosclerosis was previously treated with iliac and
      femoropopliteal Supera stenting procedures; he presented to our emergency
      department because of bilateral severe claudication recurrence, back pain, and
      right groin region swelling. Angio-computed tomography (CT) depicted 2
      pseudoaneurysms of the left common iliac artery and right SFA, due to stent
      fracture and stent intussusception, respectively. A 2-step endovascular treatment
      was planned using bilaterally covered stent-grafts to exclude vascular lesions
      from blood flow. The devices were successfully deployed without any complication.
      At 1 month, angio-CT confirmed patency of the implanted stent-grafts showing
      complete pseudoaneurysm exclusion without leaks. CONCLUSION: Endovascular
      approach can be a valid option in the treatment of pseudoaneurysms due to
      stenting procedure complications.

PMID- 30301435
TI  - Corrigendum.

PMID- 30301437
TI  - Socioeconomic inequalities in health during the Great Recession: A scoping review
      of the research literature.
AB  - AIMS: The so-called 'Great Recession' in Europe triggered widespread concerns
      about population health, as reflected by an upsurge in empirical research on the
      health impacts of the economic crisis. A growing body of empirical studies has
      also been devoted to socioeconomic inequalities in health during the Great
      Recession. The aim of the current study is to summarise this health inequality
      literature by means of a scoping review. METHODS: We have performed a scoping
      review of the research literature (English language) published in the years 2012
      2017. Only empirical papers with (a) health status measured on the individual
      level, (b) information on socioeconomic position (i.e. employment status,
      educational level, income/wealth, and/or occupational class), and (c) data from
      European countries in both pre- and post-crisis years were considered relevant.
      In total, 49 empirical studies fulfilled these inclusion criteria. RESULTS: The
      empirical findings in the 49 included studies predominantly show that
      socioeconomic inequalities in health either increased or remained stable from pre
      to post-crisis years. Two-thirds (65%) of the studies found evidence of either
      increasing or partially increasing health inequalities. Thus, people in lower
      socioeconomic strata fared worse overall in terms of health during the Great
      Recession, compared to people with higher socioeconomic status. CONCLUSIONS: The
      Great Recession in Europe tends to be followed by increasing socioeconomic
      inequalities in health. Policymakers should take note of this finding. Widening
      socioeconomic inequalities in health is a major cause of concern, in particular
      if health deterioration among 'vulnerable groups' is caused by accelerating
      cumulative disadvantages.

PMID- 30301436
TI  - Classical pediatric Hodgkin lymphoma in very young patients: the Italian
      experience.
AB  - Many studies have reported a more favorable outcome in younger patients with
      Hodgkin lymphoma (HL). The aims of this study were to find an appropriate age
      cutoff able to identify low-risk children and to describe the natural history of
      135 very young patients affected by classic HL (cHL). The best age cutoff was
      identified at 7 years of age. EFS (p = .0451) and PFS (p = .00921) were
      significantly better in the group of younger patients. The OS rate at 10 years
      was 97.0% in the younger group and 92.5% in the older one (p = .0448). However,
      age was not found to be an independent prognostic factor in multivariate analysis
      and the better prognosis in younger patients seems to be related to more
      favorable disease characteristics at presentation.

PMID- 30301438
TI  - Understanding social inequalities in Zika infection and its consequences: A model
      of pathways and policy entry-points.
AB  - The health consequences of arbovirus infections such as dengue fever (DENV),
      Chikungunya (CHIKV) and Zika (ZIKV) has in recent years become a public health
      challenge, due to failure of prevention followed by increased incidence and
      pronounced social inequality in occurrence and consequences. This motivates a
      more systematic analysis of the potential mechanisms and pathways that generate
      these inequalities. We present in the paper a model that delineates five possible
      mechanisms driving the inequality of ZIKV and congenital Zika syndrome (CZS).
      They include differential exposure to bad housing and sanitary conditions,
      differential exposure to vector density and virus, differential vulnerability to
      the health effects of exposure to virus, differential intrauterine susceptibility
      to the teratogenic effects of ZIKV infection and differential social consequences
      of caring for a disabled child. For each mechanism, we present empirical evidence
      or need for more research as well as a discussion about policy implications.

PMID- 30301439
TI  - Urinary B-cell-activating factor of the tumour necrosis factor family (BAFF) in
      systemic lupus erythematosus.
AB  - INTRODUCTION: We examined the clinical relevance of urinary concentrations of B
      cell-activating factor of the tumour necrosis factor family (BAFF) and a
      proliferation-inducing ligand (APRIL) in systemic lupus erythematosus (SLE).
      METHODS: We quantified urinary BAFF (uBAFF) by enzyme-linked immunosorbent assay
      in 85 SLE, 28 primary Sjogren syndrome (pSS), 40 immunoglobulin A nephropathy
      (IgAN) patients and 36 healthy controls (HCs). Urinary APRIL (uAPRIL) and
      monocyte chemoattractant protein 1 (uMCP-1) were also quantified. Overall and
      renal SLE disease activity were assessed using the Systemic Lupus Erythematosus
      Disease Activity Index 2000. RESULTS: uBAFF was detected in 12% (10/85) of SLE
      patients, but was undetectable in HCs, IgAN and pSS patients. uBAFF was
      detectable in 28% (5/18) of SLE patients with active nephritis vs 5/67 (7%) of
      those without ( p = 0.03), and uBAFF was significantly higher in active renal
      patients ( p = 0.02) and more likely to be detected in patients with persistently
      active renal disease. In comparison, uAPRIL and uMCP-1 were detected in 32%
      (25/77) and 46% (22/48) of SLE patients, respectively. While no difference in
      proportion of samples with detectable uAPRIL was observed between SLE, HCs and
      IgAN patients, both uAPRIL and uMCP-1 were significantly detectable in higher
      proportions of patients with active renal disease. CONCLUSIONS: uBAFF was
      detectable in a small but a significant proportion of SLE patients but not in
      other groups tested, and was higher in SLE patients with active renal disease.

PMID- 30301440
TI  - GATA3 rs3824662 gene polymorphism as possible risk factor for systemic lupus
      erythematosus.
AB  - BACKGROUND: There is no report about the association between GATA3 rs3824662
      polymorphism and systemic lupus erythematosus (SLE). OBJECTIVE: To investigate
      the possible role of GATA3 rs3824662 polymorphism as a susceptibility risk factor
      for either adult SLE (aSLE) or pediatric SLE (pSLE) and to evaluate its role in
      the development of lupus nephritis (LN) in pSLE. METHODS: Typing of GATA3
      rs3824662 polymorphism was done using real-time polymerase chain reaction for
      three groups; 104 pSLE patients, 140 aSLE patients and 436 age- and sex-matched
      healthy controls. RESULTS: Non-significant differences were found between SLE
      patients and healthy controls for the allele and genotype frequencies of GATA3
      rs3824662 ( p > 0.05). In pSLE; the AC genotype was associated with LN ( p =
      0.04); the A allele and AC genotype were associated with persistent proteinuria (
      p = 0.036 and 0.01, respectively) and both the A allele and AA genotype were
      associated with higher chronicity index ( p = 0.031 and 0.04, respectively). In
      aSLE; the C allele was associated with cellular cast ( p = 0.03) and
      thrombocytopenia ( p = 0.01). Logistic regression analysis revealed significant
      association between the AC+AA genotypes and the prediction of LN and renal active
      disease in pSLE ( p = 0.04 and 0.01, respectively). CONCLUSION: GATA3 rs3824662
      is not associated with susceptibility to SLE either in adult or in pediatric
      patients; however, in pSLE patients, the heterozygous AC genotype could be
      considered a risk factor for LN. At the same time, the AC and AA genotypes could
      be considered as predictors for LN and active renal disease. However, the small
      sample size is a limiting factor of the present study when interpreting the
      positive association.

PMID- 30301441
TI  - Succinate Dehydrogenase-Deficient Gastrointestinal Stromal Tumor With SDHC
      Germline Mutation and Bilateral Renal and Neck Cysts.
AB  - Gastrointestinal stromal tumors (GISTs) are rare in children. Succinate
      dehydrogenase (SDH)-deficient GISTs are wild type and lack KIT proto-oncogene
      receptor tyrosine kinase and platelet-derived growth factor receptor A ( KIT or
      PDGFRA) mutations. These tumors result from germline SDH mutations, somatic SDH
      mutations, or SDH epimutants. Germline mutations in SDH genes ( SDHA, SDHB, SDHC,
      or SDHD) suggest Carney-Stratakis syndrome, a paraganglioma syndrome with
      predisposition for GIST. Negative immunohistochemistry for SDHB indicates
      dysfunction of the mitochondrial complex regardless of the subunit affected. We
      present an adolescent male with an SDH-deficient GIST and SDHC germline mutation
      who developed bilateral renal cysts and neck cysts, not previously described in
      children with this mutation. Germline testing is critical when SDH mutations are
      discovered due to treatment and surveillance implications. Further investigations
      are necessary to fully define the phenotypic expression of this mutation.

PMID- 30301442
TI  - Histological Features of Shallow Placental Implantation Unify Early-Onset and
      Late-Onset Preeclampsia.
AB  - Preeclampsia is distinguishable from other hypertensive conditions of pregnancy
      by its high rates of decidual arteriopathy, the uterine type of chronic hypoxic
      placental injury, the occurrence of villous infarctions, and clusters of
      multinucleate trophoblasts in the maternal floor. To retrospectively study the
      clinical and placental phenotypes of 230 women with early-onset preeclampsia, 261
      women with late-onset preeclampsia, and 5059 women without hypertension in
      pregnancy (comparative group), 24 clinical and 46 placental phenotypes were
      statistically compared (analysis of variance, chi2 with Bonferroni correction).
      The frequency of decidual arteriopathy (both hypertrophic and atherosis),
      patterns of chronic hypoxic placental injury, villous infarction, membrane
      laminar necrosis, membrane microscopic chorionic pseudocysts, clusters of
      maternal floor multinucleated trophoblasts, excessive number of extravillous
      trophoblasts, and intervillous thrombi was strikingly higher in both late-onset
      preeclampsia and early-onset preeclampsia than in the comparative group without
      hypertension in pregnancy. All 3 patterns of chronic hypoxic placental injury
      were 2- to 3-fold more common in preeclampsia. Although the preuterine pattern
      was as common in early-onset preeclampsia as it was in late-onset preeclampsia,
      the postuterine pattern was 2-fold more common in early-onset preeclampsia, and
      chronic villitis of unknown etiology was more common in late-onset preeclampsia
      than in the other 2 groups. Features of shallow placental implantation occurred
      at the same frequency in early-onset preeclampsia as in late-onset preeclampsia,
      which reflects an underlying common pathological mechanism in both subgroups of
      preeclampsia, while hypoxic lesions and patterns of placental injury were more
      common in early-onset preeclampsia than in late-onset preeclampsia, which
      correlates with more severe clinical outcomes of the former.

PMID- 30301443
TI  - Correlation of Endoscopic and Histologic Severity Scores in Pediatric Ulcerative
      Colitis at First Presentation.
AB  - Detailed histologic scoring systems have been developed for the assessment of
      disease activity in ulcerative colitis. Literature from adult patients has shown
      some correlation between endoscopy and histology, and reproducibility of
      histologic scoring systems has also been supported. The effectiveness of
      endoscopic appearance at predicting histologic scores in pediatric patients has
      not been well studied, and none of the histologic scoring systems used in adults
      have had interobserver reproducibility assessed in pediatric patients. We
      reviewed endoscopic images and concurrent biopsies using Mayo and Geboes scores
      from the distal colon and rectum in untreated pediatric patients at the
      presentation of presumed ulcerative colitis based on clinical and endoscopic
      findings. Interobserver concordance was calculated by weighted-kappa statistic.
      The averaged histologic scores were compared to endoscopy scores using Spearman's
      coefficient. Correlation between endoscopic score and each histologic score was
      weakly to moderately positive, whereas interobserver agreement for histologic
      scores was fair to moderate, suggesting that the Geboes scoring system has value
      in pediatric patients. For each histologic parameter, the average score was lower
      than the average endoscopic score. Examination of larger pediatric cohorts,
      treated patients, correlations of clinical outcomes with individual histologic
      parameters, and alternate scoring systems may contextualize these findings.

PMID- 30301444
TI  - Variation in Platelet Delta Granules Over Time in Young Women Undergoing
      Evaluation for Heavy Menstrual Bleeding.
AB  - Delta-granule platelet storage pool deficiency (delta-PSPD) is a qualitative
      platelet function defect associated with variable bleeding phenotypes. Platelet
      electron microscopy (EM) is commonly utilized to evaluate for delta-PSPD, but
      intrapatient variability in platelet delta-granule numbers by EM is currently
      unknown. Fifteen young women aged 11 to 17 years presenting to a young women's
      hematology clinic for the evaluation of heavy menstrual bleeding underwent
      platelet EM testing at their initial hematology clinic visit and at 1 and 3
      months later. Platelet aggregation of platelet-rich plasma by light transmission
      was also performed on all patients at their initial visit. Eight patients had
      average delta-granules per platelet consistently >=2. Three patients were found
      to have average delta-granules per platelet <2 on initial testing, 2 of which
      reverted to >=2 on subsequent testing. When initial average delta-granules per
      platelet was >=2, initial repeat testing remained so in 83% (95% confidence
      interval [CI], 52%-98%) of cases and subsequent repeat testing remained so in 75%
      (95% CI, 43%-95%) of the cases. Platelet aggregation testing was abnormal in 53%
      of patients, and there was no apparent correlation between platelet EM findings
      and platelet aggregation testing. In this small group of young women presenting
      for the evaluation of bleeding symptoms, we found that almost half of the
      patients had substantial variability in platelet EM results. Given other
      identified limitations in platelet EM testing, and the intrapatient variability
      identified in this study, providers should use caution in utilizing EM in
      isolation to diagnose delta-PSPD.

PMID- 30301445
TI  - Increased reliance on a right hemispheric mechanism during idiom processing in
      adults with dyslexia.
AB  - Previous studies on adults with dyslexia (DYS) have indicated difficulties in the
      comprehension of figurative language. Using the divided visual field paradigm,
      the present study investigated the hemispheric processing of idioms among 22
      adults with DYS and 21 regular reader (RR) adults. Participants performed a
      lexical decision task for a target word related to either a literal or a
      figurative interpretation of an idiom. The results show that whereas the RR group
      demonstrated a bilateral pattern of hemispheric processing of idiomatic meanings,
      the DYS group showed a right hemisphere (RH) advantage. Furthermore, both groups
      demonstrated the typical RH advantage in processing the literal meanings of
      idioms. Our findings indicate increased recruitment of the RH in dyslexia,
      probably due to differences in cerebral language areas or weaker LH semantic
      processing.

PMID- 30301446
TI  - Comparing Preventable Hospitalizations Among Veterans With and Without Mental
      Illnesses Before and After Implementation of PACT.
AB  - OBJECTIVES:: The authors examined whether the rate of preventable
      hospitalizations among veterans with mental illness changed after implementation
      of the Department of Veterans Affairs (VA) primary care medical home-Patient
      Aligned Care Teams (PACT). METHODS:: A 12-year retrospective cohort analysis was
      conducted of data from 9,206,017 veterans seen in 942 VA primary care clinics
      between October 2003 and March 2015. Preventable hospitalizations were those
      related to ambulatory care-sensitive conditions (ACSCs), identified with ICD-9
      codes. Changes in rates of ACSC-related hospitalizations were compared between
      patients with and without mental illness in two age groups (<65, >=65). Patients
      with mental illness diagnoses were grouped as follows: depression, posttraumatic
      stress disorder, anxiety, substance use disorder, and serious mental illness.
      Interrupted time-series analysis was used to model long-term trends and detect
      deviations after PACT implementation. RESULTS:: There was an overall increase in
      mental illness diagnoses across both age groups. Among older veterans (>=65) with
      any mental illness, the rate (per 1,000 patients) of ACSC-related
      hospitalizations was five fewer in the post-PACT period, compared with the pre
      PACT period. Among younger veterans (<65), there was a slight increase in ACSC
      related hospitalizations in years 3-5 post-PACT if they had any mental illness
      (.6 per 1,000 patients), depression (.3), anxiety (1.4), or a substance use
      disorder (.6). CONCLUSIONS:: In this retrospective, observational study examining
      large systemwide changes in clinical practice, mental illness was more likely to
      be diagnosed after PACT implementation, compared with before, and results
      suggested a benefit of PACT implementation among older veterans in terms of a
      reduction in ACSC-related hospitalizations.

PMID- 30301447
TI  - Survey of Peer Support Specialists: Professional Activities, Self-Rated Skills,
      Job Satisfaction, and Financial Well-being.
AB  - As the certified peer support specialist (CPSS) workforce matures, their roles
      evolve, leading to gaps in knowledge about their activities. This study aimed to
      address these gaps through a survey on CPSS activities, self-rated skills, job
      satisfaction, and financial well-being. The project team recruited a community
      advisory board of CPSSs to lead survey development. A survey link was e-mailed to
      all known CPSSs in the state of Michigan (N=1,128), yielding 394 respondents (35%
      response rate), of whom 319 were included in the analysis. The highest skill self
      ratings included sharing recovery stories (rated very strong by 80%); the lowest
      included vocational support (rated very strong by 33%). More than 75% were
      satisfied with their workplace supportiveness; less than one-half were satisfied
      with their promotion opportunities. When asked if they could generate adequate
      funds to address a common financial shock, 115 of 301 respondents (38%) were
      "certain" they could not, suggesting financial vulnerability. These results
      support developing career ladder opportunities for CPSSs.

PMID- 30301448
TI  - Integrating Predictive Modeling Into Mental Health Care: An Example in Suicide
      Prevention.
AB  - Recent advances in statistical methods and computing power have improved the
      ability to predict risks associated with mental illness with more efficiency and
      accuracy. However, integrating statistical prediction into a clinical setting
      poses new challenges that need creative solutions. A case example explores the
      challenges and innovations that emerged at a Department of Veterans Affairs
      hospital while implementing REACH VET (Recovery Engagement and Coordination for
      Health-Veterans Enhanced Treatment), a suicide prevention program that is based
      on a predictive model that identifies veterans at statistical risk for suicide.

PMID- 30301449
TI  - Sociodemographic Characteristics and Job Satisfaction of Psychiatrists in China:
      Results From the First Nationwide Survey.
AB  - OBJECTIVE:: The aim of the study was to establish a comprehensive understanding
      of the sociodemographic characteristics of psychiatrists in China and their
      working environment and job satisfaction. METHODS:: As part of a national survey,
      the authors conducted China's first survey in 32 tertiary psychiatric hospitals,
      including administration of a structured questionnaire for psychiatrists.
      Participants also completed the Minnesota Satisfaction Questionnaire (MSQ).
      RESULTS:: Of 3,363 surveyed psychiatrists, 2,715 (81%) responded, and 2,602 (77%)
      completed the survey. Among completers, 58% were women, and 83% were ages 30-49.
      Significant differences were found in actual and expected monthly income between
      male and female psychiatrists and across various regions. The mean+/-SD MSQ score
      was 71.6+/-14.3, suggesting moderate job satisfaction. The top three reasons for
      dissatisfaction were low pay, contentious doctor-patient relationships, and a
      heavy workload. One-fifth (20%) of participants reported an intention to quit
      their jobs. MSQ score was significantly associated with younger age, shorter
      working hours, higher monthly pay, and a smaller gap between expected and actual
      pay. Being in an administrative position, having medical liability insurance, and
      not having experienced medical disputes appeared to have a positive impact on job
      satisfaction. CONCLUSIONS:: Compared with their international counterparts,
      psychiatrists in China have a low level of the job satisfaction, especially those
      in West China. Given China's increasing demand for psychiatric services, policy
      makers in China urgently need to find ways to improve the job satisfaction of
      working psychiatrists and should consider enhancements in financial compensation,
      the working environment, and malpractice insurance coverage.

PMID- 30301451
TI  - Reflections on a journey: a retrospective of the ISCB Student Council symposium
      series.
AB  - This article describes the motivation, origin and evolution of the student
      symposia series organised by the ISCB Student Council. The meeting series started
      thirteen years ago in Madrid and has spread to four continents. The article
      concludes with the highlights of the most recent edition of annual Student
      Council Symposium held in conjunction with the 25th Conference on Intelligent
      Systems for Molecular Biology and the 16th European Conference on Computational
      Biology, in Prague, in July 2017.

PMID- 30301452
TI  - Adherence to the neonatal resuscitation algorithm for preterm infants in a
      tertiary hospital in Spain.
AB  - BACKGROUND: There is evidence that delivery room resuscitation of very preterm
      infants often deviates from internationally recommended guidelines. There were no
      published data in Spain regarding the quality of neonatal resuscitation.
      Therefore, we decided to evaluate resuscitation team adherence to neonatal
      resuscitation guidelines after birth in very preterm infants. METHODS: We
      conducted an observational study. We video recorded resuscitations of preterm
      infants < 32 weeks' gestational age and evaluated every step during resuscitation
      according to a score-sheet specifically designed for this purpose, following
      Carbine's method, where higher scores indicated that more intense resuscitation
      maneuvers were required. We divided the score achieved by the total possible
      points per patient to obtain the percentage of adherence to the algorithm. We
      also compared resuscitations performed by staff neonatologists to those performed
      by pediatricians on-call. We compared percentages of adherence to the algorithm
      with the Chi-square test for large groups and Fisher's exact test for smaller
      groups. We compared assigned Apgar scores with those given after analyzing the
      recordings and described them by their median and interquartile range. We
      measured the interrater agreement between Apgar scores with Cohen's kappa
      coefficient. Linear and logarithmic regressions were drawn to characterize the
      pattern of algorithm adherence. Statistical analysis was performed using SPSS
      V.20. A p-value < 0.05 was considered significant. Our Hospital Ethics Committee
      approved this project, and we obtained parental written consent beforehand.
      RESULTS: Sixteen percent of our resuscitations followed the algorithm. The number
      of mistakes per resuscitation was low. Global adherence to the algorithm was
      80.9%. Ventilation and surfactant administration were performed best, whereas
      preparation and initial steps were done with worse adherence to the algorithm.
      Intubation required, on average, 2.2 attempts; success on the first attempt
      happened in 33.3% of cases. Only 12.5% of intubations were achieved within the
      allotted 30 s. Many errors were attributable to timing. Resuscitations led by
      pediatricians on-call were performed as correctly as those by staff
      neonatologists. CONCLUSIONS: Resuscitation often deviates from the
      internationally recognized algorithm. Perfectly performed resuscitations are
      infrequent, although global adherence to the algorithm is high. Neonatologists
      and pediatricians need intubation training.

PMID- 30301453
TI  - Disability, mental health, sexual orientation and gender identity: understanding
      health inequity through experience and difference.
AB  - BACKGROUND: This paper focuses on inequities in health in the context of
      disability, mental health, sexual orientation and gender identity (The authors'
      location outside of these identities is acknowledged as a serious limitation in
      discussing experience as a framework to understand health inequity in the
      dimensions of disability, mental health, sexual orientation and gender identity).
      These are dimensions that lead to health inequity primarily through the pathways
      of stigma and discrimination. The aim here is to distinguish the unique
      characteristics of these groups and thereby try and articulate a new
      understanding of health and health equity with identity and difference in the
      foreground. We aim to bring attention to experience as a crucial parameter to
      discuss health equity in this context. DISCUSSION: Health inequity can be
      approached in two ways. One is to look at the lacuna in the current public health
      discourse in addressing the specific health concerns along the dimensions of
      disability, mental health, sexual orientation and gender identity. The second
      approach involves a more organic way of taking on board the concerns of these
      groups, rather than as after-thoughts; this involves a framework that gives a
      central role to the lived experience of stigma and discrimination. The dimensions
      of disability, mental health, sexual orientation and gender identity affect
      health inequities constitutively, instrumentally through co-morbidities, and
      through stigma either directly or indirectly. Experience of stigma also forms the
      basis of identities and the difference between identities, which emerges as an
      important concept in the articulation of health inequities beyond measurable
      gaps. Recognition and representation of these differences then form the basis of
      an inclusive articulation on health. CONCLUSION: The centrality of difference and
      experience prompts us to problematise the idea of equity that rests on 'avoidable
      and unfair', 'differentials' and even to argue that such a definition based on
      differentials, used in a quantitative sense, seriously limits our understanding
      of health inequity. Health equity will therefore not merely mean 'closing
      avoidable health gaps,' but mandate an inclusive social arrangement that
      celebrates difference.

PMID- 30301454
TI  - Standardization and application of a modified RFLP-PCR methodology for analysis
      of polymorphisms linked to treatment resistance in Ancylostoma braziliense.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) in codons 167, 198 and 200 of
      the beta-tubulin isotype 1 gene are associated with benzimidazoles resistance in
      many helminths. Codon 167 mutation has never been described in hookworms;
      however, polymorphisms in codons 198 and 200 have been described for Ancylostoma
      caninum and Necator americanus. These mutations have never been investigated in
      Ancylostoma braziliense; therefore, it is not known if they are present in this
      species and whether they are correlated with treatment resistance. The RFLP-PCR
      technique has been used to analyze these polymorphisms in some nematodes, but
      depending on the species, these alterations do not create or eliminate any
      restriction enzyme cleavage site, making it impossible to use this technique.
      Here, we describe the standardization and application of a modified RFLP-PCR
      technique for detecting polymorphisms in individual A. braziliense worms
      recovered from naturally infected dogs in two Brazilian states. RESULTS: The
      molecular techniques used were sensitive, specific, and easy to apply. To our
      knowledge, we report for the first time the presence of a polymorphism at codon
      198 of the beta-tubulin gene of A. braziliense (1/81; 95% CI: 0-3.69%).
      CONCLUSIONS: It is not known whether the presence of the mutation in codon 198 of
      the beta-tubulin gene of A. braziliense has importance for this parasite.
      However, based on studies of other helminths, it is possible that this
      polymorphism is directly related to the resistance to benzimidazoles. This may be
      a major concern, since this nematode has considerable relevance as a parasite of
      canids and felids and as one of the agents of cutaneous larva migrans in humans.
      Standardized methodologies will be useful for screening for polymorphisms in the
      beta-tubulin gene of canine hookworms in a broader population. The method could
      also be adapted for the analysis of other SNPs in other nematode species.

PMID- 30301455
TI  - A health equity research agenda for India: results of a consultative exercise.
AB  - BACKGROUND: This paper describes the process and outcome of a consultative
      exercise undertaken to develop a medium-term agenda for the next decade, and to
      identify a short list of immediate priorities for health equity research in
      India. This exercise was undertaken over 2014-2017 as part of 'Closing the Gap:
      Health Equity Research Initiative in India', implemented by the Achutha Menon
      Centre for Health Science Studies, at the Sree Chitra Tirunal Institute of
      Medical Sciences and Technology, Trivandrum, in south India. METHODS: We adopted
      a five-step process for the agenda- and priority-setting exercise. The first
      step, which lasted for approximately 1 year, consisted of a synthesis of evidence
      on health inequities in India produced during 2000-2014 and identification of
      gaps. In the second step, we shared the evidence gaps identified and engaged with
      diverse stakeholders to develop the research agenda through face-to-face and
      online consultations. In step three, we consolidated the research agenda and
      identified continuing gaps. Key informant consultations by phone or email with
      experts in the areas where gaps were identified constituted the fourth step. In
      the fifth and final step, we organised an expert group consultation to review the
      agenda and identify immediate research priorities through a consensus process.
      Overall, approximately 220 persons participated in the entire process, and
      consisted of persons from diverse disciplines and sectors. RESULTS: The research
      agenda and immediate priorities that emerged may be categorised into four themes,
      namely (1) descriptive research on the extent, nature and time trends in health
      inequities; (2) explanatory research on the pathways through which health
      inequities are created, and the political or policy environment that facilitates
      the process; (3) explanatory research that examines how health systems facilitate
      or mitigate inequities in healthcare; and (4) intervention research on
      initiatives that helped to mitigate health inequities, and examines the
      contributing factors. CONCLUSION: The strength of this research agenda is that it
      was developed through a broad-based consultation with stakeholders representing
      diverse disciplines, sectors and constituencies. The use of this agenda will help
      generate evidence that will facilitate India moving closer to the Sustainable
      Development Goal of leaving no one behind.

PMID- 30301456
TI  - Castleman disease of the hyaline vascular variant transforming to POEMS syndrome
      as endpoint: a case report.
AB  - BACKGROUND: POEMS syndrome is a rare neoplastic syndrome reflected by plasma cell
      disorder. It is composed by polyneuropathy, organomegaly, endocrinopathy,
      monoclonal protein, and skin changes. It is also reported to associate with
      Castleman disease. The early identification and treatment are pivotal to reduce
      the morbidity and mortality. CASE PRESENTATION: Here we report a 66-year-old man
      with treated Castleman disease developing with sequential presence of
      endocrinopathy polyneuropathy, skin changes, organomegaly and extravascular
      volume overload within 18 years, which was finally confirmed as POEMS syndrome by
      positive monoclonal protein. He was thereafter successfully treated with
      prednisone and azathioprine as primary therapy and thalidomide as maintenance
      therapy. CONCLUSION: The diagnosis of POEMS is based on a cluster of disorder
      involved in varied organs. We report a rare case that triggers the need to
      consider POEMS syndrome diagnosis for patients carrying Castleman disease and
      polyneuropathy.

PMID- 30301457
TI  - Globalisation and neoliberalism as structural drivers of health inequities.
AB  - In this paper, we draw upon and build on three presentations which were part of
      the plenary session on 'Structural Drivers of Health Inequities' at the National
      Conference on Health Inequities in India: Transformative Research for Action,
      organised by the Achutha Menon Centre for Health Science Studies in Trivandrum,
      India. The three presentations discussed the influential role played by
      globalisation and neoliberalism in shaping economic, social and political
      relationships across developed and developing countries. The paper further argues
      that the twin process of globalisation and liberalisation have been important
      drivers of health inequities. The first segment of the paper attempts a broader
      conceptualisation of neoliberalism beyond the economic realm. Using Stephanie Lee
      Mudge's conceptualisation (Soc Econ Rev 6:703-3, 2008) we have analysed how the
      political, bureaucratic and intellectual domains of neoliberalism have
      intersected and redefined the role of state and commercialised health services
      leading to inequities. Neoliberal ideas have reconfigured the role and changed
      the priorities of non-governmental organisations resulting in a fracture within
      this movement. n the second segment, we focus on the rise of American philanthro
      capitalism, and how the two major foundations, the Rockefeller Foundation (early
      twentieth century) and the Bill and Melinda Gates Foundation (twenty-first
      century), have shaped the ideology of institutions engaged in international
      health and influenced the global health agenda. We discuss how the activities of
      philanthro-capitalists have transformed the architecture of health governance
      through their top-down organisational culture and deficit of structures to ensure
      accountability. The third and final segment of the paper focuses on how
      neoliberalism as a political project and cultural movement has forged alliances
      with conservative politics and religious fundamentalisms, resulting in negative
      consequences for women and other marginalised groups. These alliances have
      resulted in the control of women's bodies and contributed to the reversal of hard
      won rights for health and gender justice in many parts of the world.

PMID- 30301458
TI  - Syringomyelia-like syndrome in neuromyelitis optica spectrum disorder complicated
      with Sjogren's syndrome: a case report.
AB  - BACKGROUND: Besides CSF-flow obstruction, syringomyelia is associated with
      inflammatory spinal cord lesions. However, syringomyelia-like syndrome
      concomitant with neuromyelitis optica spectrum disorder (NMOSD) and primary
      Sjogren's syndrome (pSS) is extremely rare. Here, we would like to report a case
      of a patient with syringomyelia-like syndrome in NMOSD complicated with Sjogren's
      Syndrome. CASE PRESENTATION: A 64-old male Han Chinese, presented with three
      episodes of acute demyelinating processes in the central nervous system within 5
      years. Firstly, he presented with ascending left lower extremity weakness and
      numbness, and initially progressive loss of vision in the right eye before 5
      years, and subsequently in the right eye 2 months later. High dose corticosteroid
      therapy was prescribed for this attack. Second, he suffered from refractory
      gastrointestinal symptoms. such as nausea, vomiting, abdominal pain and early
      satiety. After the second episode, he received long-term azathioprine and
      prednisone treatment in low dosages. Six months before admission, he developed
      the lower back pain and numbness in lower limbs, and urinary incontinence. This
      time, he complained of acute onset of right lower limb paralysis, paresthesia and
      urinary incontinence. MRI of the spine revealed a syringomyelia extending from
      the C7 to T4 levels with serum positive anti-aquaporin-4 antibodies (AQP4-Ab)
      (indirect immunofluorescence on AQP4 transfected cells). he was serologically
      positive for both anti-Sjogren's syndrome-related antigen A and B antibodies and
      there was reduced salivary flow on scintigraphy. Lip salivary gland (LSG)
      biopsies were graded (grade four lymphocytic infiltration) according to the
      Chisholm and Mason classification system and by morphometric analysis. And
      finally, diagnosed as syringomyelia-like syndrome in NMOSD complicated with
      Sjogren's syndrome. CONCLUSIONS: Although extremely rare, This index patient
      highlights that syringomyelia could be associated with underlying NMOSD and pSS,
      and autoimmune disorders should be considered in the initial differential
      diagnosis, This is very helpful for the therapeutic implications and evaluating
      curative effect.

PMID- 30301459
TI  - Coating the plate with antibiotic cement to treat early infection after fracture
      fixation with retention of the implants: a technical note.
AB  - BACKGROUND: Local antibiotic therapy has gained increasing attraction in the
      prevention and treatment of fracture infection. However, no reports have used
      local antibiotic therapy in the management of early infection after fracture
      fixation with retention of implants. METHODS: The present surgical technique
      report the use of antibiotic impregnated bone cement in the management of early
      infection after fracture fixation. Initially, the fractures were fixed with
      plates. The average time from initial procedure to debridement was15 days (range
      9 to 25 days). The infections were treated with irrigation, debridement, and
      retention of the implant. The lateral surface of the plates was coated with
      antibiotic cement and the bone defect was filled with antibiotic cement spacer
      after thorough debridement. RESULTS: Ten patients underwent this technique. The
      mean follow-up was 2.0 years (range 6 months to 4 years). The bone union rate was
      100%, and the average time to bone healing was5.5 months.There was recurrence of
      infection in one patient before bone healing, but the implants were left in place
      until bone healed, and the infection was eradicated after implant removal.
      CONCLUSION: Coating the plate with antibiotic cement is a simple technique which
      may play a role in the management of early infection after fracture fixation.

PMID- 30301460
TI  - Rising plasminogen activator inhibitor-1 and hypoadiponectinemia characterize the
      cardiometabolic biomarker profile of women with recent gestational diabetes.
AB  - BACKGROUND: Gestational diabetes (GDM) and milder gestational impaired glucose
      tolerance (GIGT) identify women at risk of developing type 2 diabetes and
      cardiovascular disease later in life. Accordingly, the postpartum years after
      gestational dysglycemia can provide insight into early events in the natural
      history of these disorders. We thus sought to prospectively evaluate the
      relationship between gestational glucose tolerance and emerging cardiometabolic
      biomarkers [adiponectin, chemerin, retinol-binding protein-4 (RBP-4), C-reactive
      protein (CRP), plasminogen activator inhibitor-1 (PAI-1)] at both 1- and 3-years
      postpartum in a cohort reflecting the full spectrum of gestational dysglycemia
      (from normal to GIGT to GDM). METHODS: Three-hundred-and-thirty-nine women
      completed a glucose challenge test (GCT) and oral glucose tolerance test (OGTT)
      in pregnancy, which identified 4 gestational glucose tolerance groups: GDM (n =
      105); GIGT (n = 59); abnormal GCT with normal OGTT (n = 99); and normal GCT with
      normal OGTT (n = 76). At 1- and 3-years postpartum, the women underwent repeat
      OGTT with measurement of biomarkers (adiponectin/chemerin/RBP-4/CRP/PAI-1).
      RESULTS: Serum adiponectin was lower in women with GDM and GIGT at both 1-year
      and 3-years (both P <= 0.002), whereas chemerin, RBP-4, CRP and PAI-1 showed no
      differences across the 4 groups. Importantly, the change in PAI-1 between 1- and
      3-years progressively increased from the normal GCT group to the abnormal GCT
      group to GIGT to GDM (P = 0.03). Indeed, both GDM (t = 2.98, P = 0.003) and GIGT
      (t = 2.14, P = 0.03) independently predicted an increase in PAI-1 from 1- to 3
      years postpartum. CONCLUSIONS: Hypoadiponectinemia and rising PAI-1 over time are
      early features of the cardiometabolic biomarker profile of women with recent
      gestational dysglycemia.

PMID- 30301461
TI  - A resonance Rayleigh scattering sensor for sensitive differentiation of telomere
      DNA length and monitoring special motifs (G-quadruplex and i-motif) based on the
      Ag nanoclusters and NAND logic gate responding to chemical input signals.
AB  - BACKGROUND: Differentiation of telomere length is of vital importance because
      telomere length is closely related with several deadly diseases such as cancer.
      Additionally, G-quadruplex and i-motif formation in telomeric DNA have been shown
      to act as a negative regulator of telomere elongation by telomerase in vivo and
      are considered as an attractive drug target for cancer chemotherapy. RESULTS: In
      this assay, Ag nanoclusters templated by hyperbranched polyethyleneimine (PEI-Ag
      NCs) are designed as a new novel resonance Rayleigh scattering (RRS) probe for
      sensitive differentiation of telomere length and monitoring special motifs (G
      quadruplex and i-motif). In this assay, free PEI-Ag NC probe or DNA sequence
      alone emits low intensities of RRS, while the formation of PEI-Ag NCs/DNA
      complexes yields greatly enhanced RRS signals; however, when PEI-Ag NCs react
      with G-quadruplex or i-motif, the intensities of RRS exhibit slight changes. At
      the same concentration, the enhancement of RRS signal is directly proportional to
      the length of telomere, and the sensitivity of 64 bases is the highest with the
      linear range of 0.3-50 nM (limit of detection 0.12 nM). On the other hand, due to
      the conversion of telomere DNA molecules among multiple surrounding conditions, a
      DNA logic gate is developed on the basis of two chemical input signals (K+ and
      H+) and a change in RRS intensity as the output signal. CONCLUSION: Our results
      indicate that PEI-Ag NCs can serve as a novel RRS probe to identify DNA length
      and monitor G-quadruplex/i-motif through the different increasing degrees of RRS
      intensity. Meanwhile, the novel attributes of the nanoprobe stand superior to
      those involving dyes or labeled DNA because of no chemical modification, low
      cost, green, and high efficiency.

PMID- 30301462
TI  - Re-infection rates and clinical outcomes following arthrodesis with
      intramedullary nail and external fixator for infected knee prosthesis: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Knee arthrodesis with intramedullary (IM) nail or external fixator
      (EF) is the most reliable therapeutic option to achieve definitive infection
      control in patients with septic failure of total knee arthroplasty (TKA). The
      first aim of this study was to compare re-infection rates following knee
      arthrodesis for periprosthetic joint infection (PJI) with IM nail or EF. The
      second aim was to compare rates of radiographic union, complication, and re
      operation as well as clinical outcomes. METHODS: A systematic search was
      performed in electronic databases for longitudinal studies of PJIs (minimum ten
      patients; minimum follow-up = 1 year) treated by knee arthrodesis with IM nail or
      EF. Studies were also required to report the rate of re-infection as an outcome
      measure. Eligible studies were meta-analyzed using random-effect models. RESULTS:
      The rate (95% confidence intervals) of re-infection was 10.6% (95% CI 7.3 to
      14.0) in IM nail arthrodesis studies. The corresponding re-infection rate for EF
      was 5.4% (95% CI 1.7 to 9.1). This difference was significant (p = 0.009). The
      use of IM nail resulted in more advantages than EF for frequency of major
      complications and limb shortening. Other postoperative clinical and radiographic
      outcomes were similar for both surgical strategies. CONCLUSIONS: The available
      evidence from the aggregate published data suggests that knee arthrodesis with EF
      in the specific context of PJI has a reduced risk of re-infection in comparison
      with the IM nail strategy. The use of IM nail is more effective for the
      complication rate and shortening of the affected limb.

PMID- 30301463
TI  - Isolation of anticancer constituents from Cucumis prophetarum var. prophetarum
      through bioassay-guided fractionation.
AB  - BACKGROUND: Cucumis prophetarum var. prophetarum is used in Saudi folk medicine
      for treating liver disorders and grows widely between Abha and Khamis Mushait
      City, Saudi Arabia. METHODS: Bioassay-guided fractionation and purification were
      used to isolate the main active constituents of Cucumis prophetarum var.
      prophetarum fruits. These compounds were structurally elucidated using NMR
      spectroscopy, mass spectral analyses and x-ray crystallography. All fractions,
      sub-fractions and pure compounds were screened for their anticancer activity
      against six cancer cell lines. RESULTS: The greatest cytotoxic activity was found
      to be in the ethyl acetate fraction, resulting in the isolation of five
      cucurbitacin compounds [E, B, D, F-25 acetate and Hexanorcucurbitacin D]. Among
      the cucurbitacins that were isolated and tested cucurbitacin B and E showed
      potent cytotoxicity activities against all six human cancer cell lines.
      CONCLUSION: Human breast cancer cell lines were found to be the most sensitive to
      cucurbitacins. Preliminary structure activity relationship (SAR) for cytotoxic
      activity of Cucurbitacins against human breast cancer cell line MDA-MB-231 has
      been reported.

PMID- 30301464
TI  - Profile of cardiac lipid metabolism in STZ-induced diabetic mice.
AB  - BACKGROUND: Lipotoxicity contributes to diabetic myocardial disease. In this
      study, we investigated the lipid species contributing to lipotoxicity and the
      relationship with peroxisomal beta-oxidation in the heart of diabetic mice.
      METHODS: Male C57BL/6 mice were randomly divided into a Diabetic group
      (intraperitoneal injection of STZ) and a Control group (saline). Cardiac function
      indexes [ejection fraction (EF%) and fractional shortening (FS%)] were evaluated
      by echocardiography. Morphological changes in the myocardial tissues and
      mitochondria were assessed by electron microscopy following hematoxylin and eosin
      staining. Blood myocardial injury indexes and lipids were measured using an
      automatic biochemical analyzer. Cardiac ATP levels were analyzed using a
      commercially available kit. mRNA levels of glucose transporter 4 (GLUT4), fatty
      acid binding protein 3 (FABP3), palmitoyl transferase 1alpha (CPT-1alpha), acyl
      CoA oxidase 1 (AOX1), D-bifunctional protein (DBP), 3-ketoacyl-CoA thiolase A
      (THLA), uncoupling protein (UCP) 2 and UCP3 were investigated by quantitative
      reverse-transcription polymerase chain reaction. FABP3 protein expression was
      analyzed by Western blotting. Non-targeted metabolomics by LC-MS/MS was applied
      to evaluate profile of lipid metabolism in heart. RESULTS: Compared with
      controls, EF% and FS% were significantly reduced in diabetic mice. Furthermore,
      blood myocardial injury indexes and lipids, as well as myocardial mitochondrial
      cristae fusion were significantly increased. In the diabetic heart, GLUT4
      expression was decreased, while expression of FABP3, CPT-1alpha, AOX1, DBP, THLA,
      UCP2 and UCP3 was increased, and ATP levels were reduced. In total, 113 lipids
      exhibited significant differential expression (FC > 2, P < 0.05) between the two
      groups, with sphingolipid metabolism identified as the top-ranking affected
      canonical pathway. In the diabetic heart, long-chain hydroxyl-acylcarnitines
      (8/8) and acylcarnitines (6/11), triglycerides (2/5), and diacyglycerol (3/7)
      were upregulated, while very long-chain polyunsaturated fatty acids (PUFAs) (5/6)
      including eicosapentaenoate, docosahexaenoate, phosphocholine (11/19),
      lysophosphocholine (5/9), phosphoethanolamine (7/11), lysophosphoethanolamine
      (7/10), phosphatidylglycerol (6/8), phosphoserine (6/8), phosphatidylinositol
      (2/2), phosphatidic acid (1/1), lysophosphatidic acid (1/1) and sphingomyelin
      (6/6) were downregulated. CONCLUSIONS: Our data suggest that the increase in
      toxic lipid species and decreased in PUFAs undergoing peroxisomal beta-oxidation,
      combined with the reduction in phospholipids cause mitochondrial injury and
      subsequent uncoupling of phosphorylation and ATP deficiency; thereby leading to
      diabetic heart dysfunction.

PMID- 30301465
TI  - Multidisciplinary approach for treatment of a dentigerous cyst -
      marsupialization, orthodontic treatment, and implant placement: a case report.
AB  - BACKGROUND: Dentigerous cysts are common odontogenic cysts associated with
      unerupted teeth. We describe a previously unreported case of a multidisciplinary
      approach using surgical, orthodontic, and implant treatment to establish the
      occlusion for a patient with a maxillary dentigerous cyst. CASE PRESENTATION: An
      18-year-old Japanese woman visited our hospital with a chief complaint of
      gingival swelling in her anterior maxillary region, midline diastema, and tooth
      crowding. Her main symptom was this gingival swelling. A panoramic radiograph
      revealed a radiolucent area, 30 mm in diameter, round in shape, and with well
      demarcated margins including the maxillary canine. Computed tomography revealed a
      cystic cavity filled with homogeneous fluid of the same density as water, and a
      distolingually inclined canine. Our clinical diagnosis was maxillary dentigerous
      cyst with an unerupted distolingually inclined canine. The selected treatment was
      marsupialization of the dentigerous cyst, followed by orthodontic traction of the
      unerupted canine, and simultaneous orthodontic treatment of the midline diastema
      and tooth crowding. The orthodontic traction failed because the canine did not
      erupt completely, and the canine was extracted. The treatment plan was then
      changed to implant treatment after the tooth crowding and midline diastema had
      been improved. Because the alveolar ridge width was inadequate, the implant was
      placed after a two-stage implant treatment; therefore, a satisfactory occlusion
      could be achieved. Our patient did not experience any complications, and the cyst
      has not recurred. A radiograph taken 7 years after marsupialization of the
      dentigerous cyst revealed that the cystic cavity had been replaced by new bone.
      CONCLUSIONS: In general, orthodontic traction of an unerupted tooth after
      marsupialization should be the best option. However, if orthodontic traction
      fails, a multidisciplinary approach involving implant treatment may be necessary.
      We describe a case in which a multidisciplinary approach involving surgical,
      orthodontic, and implant treatment was used to establish a satisfactory occlusion
      for a patient with a dentigerous cyst.

PMID- 30301466
TI  - Neurophysiological signals as predictive translational biomarkers for Alzheimer's
      disease treatment: effects of donepezil on neuronal network oscillations in
      TgF344-AD rats.
AB  - BACKGROUND: Translational research in Alzheimer's disease (AD) pathology provides
      evidence that accumulation of amyloid-beta and hyperphosphorylated tau,
      neuropathological hallmarks of AD, is associated with complex disturbances in
      synaptic and neuronal function leading to oscillatory abnormalities in the
      neuronal networks that support memory and cognition. Accordingly, our recent
      study on transgenic TgF344-AD rats modeling AD showed an age-dependent reduction
      of stimulation-induced oscillations in the hippocampus, and disrupted long-range
      connectivity together with enhanced neuronal excitability in the cortex,
      reflected in greatly increased expression of high-voltage spindles, an epileptic
      absence seizure-like activity. To better understand the translational value of
      observed oscillatory abnormalities in these rats, we examine here the effects of
      donepezil, an acetylcholine esterase inhibitor clinically approved for AD
      treatment. METHODS: Brainstem nucleus pontis oralis stimulation-induced
      hippocampal oscillations were recorded under urethane anesthesia in adult (6
      month-old) and aged (12-month-old) TgF344-AD and wild-type rats. Spontaneous
      cortical activity was monitored in a cohort of freely behaving aged rats
      implanted with frontal and occipital cortical electroencephalography (EEG)
      electrodes. RESULTS: Subcutaneous administration of donepezil significantly
      augmented stimulation-induced hippocampal theta oscillation in aged wild-type
      rats and both adult and aged TgF344-AD rats, which have been previously shown to
      have diminished response to nucleus pontis oralis stimulation. Moreover, in adult
      TgF344-AD rats, donepezil also significantly increased theta phase-gamma
      amplitude coupling in the hippocampus during stimulation. However, neither of
      these effects were significantly changed in adult wild-type rats. Under freely
      behaving conditions, donepezil treatment had the opposite effect on cortical
      oscillatory connectivity in TgF344-AD and wild-type rats, and it reduced the
      occurrence of high-voltage spindle activity in TgF344-AD rats. CONCLUSIONS:
      Together, these results imply that pharmacologically enhancing cholinergic tone
      with donepezil could partially reverse oscillatory abnormalities in TgF344-AD
      rats, which is in line with its clinical effectiveness in AD patients. Therefore,
      our study suggests good translational opportunities for these neurophysiological
      signals recorded in TgF344-AD rats, and their application could be considered in
      drug discovery efforts for developing therapies with disease-modifying potential.

PMID- 30301467
TI  - Infant progressive colonic stenosis caused by antibiotic-related Clostridium
      difficile colitis - a case report and literature review.
AB  - BACKGROUND: Colonic stenosis is a rare cause of pediatric intestinal obstruction.
      The root cause underlying colonic stenosis is unclear and there is no fixed
      operation. CASE PRESENTATION: We reported on a male infant with progressive
      colonic stenosis caused by antibiotic-related colitis. The infant was admitted to
      our hospital with pneumonia but developed progressive abdominal distension and
      diarrhea following antibiotic treatment with meropenem. Initial testing of stool
      culture showed a Clostridium difficile infection. Additional testing with barium
      enema imaging showed stenosis at the junction of the sigmoid and descending colon
      at first and another stenosis occurred at the right half of the transverse colon
      3 weeks later. Staged surgical treatment was performed with primary resections of
      the two parts suffering stenosis, ileostomy, and secondary intestinal
      anastomosis. A pathological exam then confirmed the diagnosis of colonic stenosis
      and the patient had an uneventful recovery and has been recovering well as
      evidenced by the 1-year follow-up. CONCLUSIONS: Based on a review of the
      literature and our case report, we found that progressive colonic stenosis caused
      by colitis due to antibiotic-related Clostridium difficile infection is rare in
      infants. Infants with colitis and repeated abdominal distention, vomiting, and
      constipation should be treated with the utmost caution and screened. Despite
      this, clinical manifestations depended on the severity of the stenosis. Barium
      enema, colonoscopy, laprascopy or laparotomy and colonic biopsy are helpful for
      diagnosis and differential diagnosis. While both one-stage and multiple-stage
      operations are feasible, a staged operation should be used for multiple colonic
      stenoses.

PMID- 30301468
TI  - Young man with severe metabolic acidosis after transformer oil ingestion: a case
      report.
AB  - BACKGROUND: Transformer oil is used in oil-filled transformers for its insulating
      as well as coolant properties. Transformer oil ingestion for attempted suicide is
      seldom heard of. Our patient's case presented us with a major diagnostic as well
      as treatment challenge because we encountered such a case for the first time and
      were totally unaware of the fact that methanol might make up the main component
      of an aged transformer oil. CASE PRESENTATION: A 19-year-old Pakistani/Asian man
      was brought to our hospital with altered sensorium. He was found to have elevated
      anion gap acidosis, increased osmolal gap, and acute kidney injury. He had no
      evidence of rhabdomyolysis or hemolysis. Computed tomography of his head showed
      cerebral edema. He was resuscitated with intravenous fluids and bicarbonate.
      Three days later, he confessed taking transformer oil with suicidal intention.
      His clinical picture mimicked acute methanol intoxication. With an initial
      improvement in his neurological status, he started complaining of constant
      headache with episodes of agitation and delirium. His renal function continued
      worsening despite an adequate urine output. He showed a remarkable improvement in
      his neurological state after just one session of hemodialysis. CONCLUSIONS: There
      is evidence that aged transformer oil contains methanol, and a patient who
      consumes it can present with features mimicking acute methanol intoxication.

PMID- 30301469
TI  - Profiling the airway in the macaque model of tuberculosis reveals variable
      microbial dysbiosis and alteration of community structure.
AB  - BACKGROUND: The specific interactions of Mycobacterium tuberculosis (Mtb), the
      causative agent of tuberculosis (TB), and the lung microbiota in infection are
      entirely unexplored. Studies in cancer and other infectious diseases suggest that
      there are important exchanges occurring between host and microbiota that
      influence the immunological landscape. This can result in alterations in immune
      regulation and inflammation both locally and systemically. To assess whether Mtb
      infection modifies the lung microbiome, and identify changes in microbial
      abundance and diversity as a function of pulmonary inflammation, we compared
      infected and uninfected lung lobe washes collected serially from 26 macaques by
      bronchoalveolar lavage over the course of infection. RESULTS: We found that Mtb
      induced an initial increase in lung microbial diversity at 1 month post infection
      that normalized by 5 months of infection across all macaques. Several core genera
      showed global shifts from baseline and throughout infection. Moreover, we
      identified several specific taxa normally associated with the oral microbiome
      that increased in relative abundance in the lung following Mtb infection,
      including SR1, Aggregatibacter, Leptotrichia, Prevotella, and Campylobacter. On
      an individual macaque level, we found significant heterogeneity in both the
      magnitude and duration of change within the lung microbial community that was
      unrelated to lung inflammation and lobe involvement as seen by positron emission
      tomography/computed tomography (PET/CT) imaging. By comparing microbial
      interaction networks pre- and post-infection using the predictive algorithm SPIEC
      EASI, we observe that extra connections are gained by Actinomycetales, the order
      containing Mtb, in spite of an overall reduction in the number of interactions of
      the whole community post-infection, implicating Mtb-driven ecological
      reorganization within the lung. CONCLUSIONS: This study is the first to probe the
      dynamic interplay between Mtb and host microbiota longitudinally and in the
      macaque lung. Our findings suggest that Mtb can alter the microbial landscape of
      infected lung lobes and that these interactions induce dysbiosis that can disrupt
      oral-airway boundaries, shift overall lung diversity, and modulate specific
      microbial relationships. We also provide evidence that this effect is
      heterogeneous across different macaques. Overall, however, the changes to the
      airway microbiota after Mtb infection were surprisingly modest, despite a range
      of Mtb-induced pulmonary inflammation in this cohort of macaques.

PMID- 30301471
TI  - The knowledge and attitudes of general practitioners to the assessment and
      management of pain in people with dementia.
AB  - BACKGROUND: Pain in people with dementia is underdiagnosed and undertreated.
      General practitioners (GPs) play a pivotal role in dementia care but their
      perspectives on pain in people with dementia remains under-researched. The aim of
      this study was to explore GPs' knowledge and attitudes towards pain assessment
      and management in people with dementia. METHODS: This was a descriptive cross
      sectional study. A questionnaire was adapted from a previous study and piloted
      with 5 GPs. The questionnaire was posted to a census sample of all GPs in Cork
      city and county in the southern region of Ireland. The questionnaire collected
      demographic information, responses to a series of Likert-type statements
      assessing GPs' knowledge and attitudes, and provided an opportunity for the GP to
      give qualitative feedback on their experiences of managing pain in dementia. SPSS
      v25 was used for statistical analysis. Qualitative responses were thematically
      analysed. RESULTS: Of the 320 questionnaires posted, 157 completed questionnaires
      were returned (response rate of 49%). The sample was representative of GPs
      nationally in terms of years in GP practice and practice location. Over two
      thirds (108/157) of respondents had a nursing home commitment. Only 10% of
      respondents (16/157) were aware of any dementia-specific pain assessment tools.
      The larger the nursing home commitment of the GP the more likely they were to be
      familiar with these tools (p = 0.048). The majority of respondents (113/157)
      believed people with dementia could not self-report pain. Respondents were
      uncertain about the safety of using opioid medications to treat pain in people
      with dementia with only 51.6% agreeing that they were safe. The qualitative
      comments highlighted the importance the GPs placed on surrogate reports of pain,
      GPs' uncertainty regarding the value of formal pain assessment tools and the
      challenges caused by under-resourcing in general practice. CONCLUSION: This study
      has highlighted aspects of pain assessment and management in dementia that GPs
      find challenging. Guidance on pain assessment and management in people with
      dementia do not appear to be translating into clinical practice. The findings
      will inform educational interventions being developed by our research team as
      part of the implementation of the Irish national dementia strategy. The knowledge
      and attitudes of general practitioners to the assessment and management of pain
      in people with dementia.

PMID- 30301470
TI  - Specific microRNA signatures in exosomes of triple-negative and HER2-positive
      breast cancer patients undergoing neoadjuvant therapy within the GeparSixto
      trial.
AB  - BACKGROUND: The focus of this study is to identify particular microRNA (miRNA)
      signatures in exosomes derived from plasma of 435 human epidermal growth factor
      receptor 2 (HER2)-positive and triple-negative (TN) subtypes of breast cancer
      (BC). METHODS: First, miRNA expression profiles were determined in exosomes
      derived from the plasma of 15 TNBC patients before neoadjuvant therapy using a
      quantitative TaqMan real-time PCR-based microRNA array card containing 384
      different miRNAs. Forty-five miRNAs associated with different clinical parameters
      were then selected and mounted on microRNA array cards that served for the
      quantification of exosomal miRNAs in 435 BC patients before therapy and 20
      healthy women. Confocal microscopy, Western blot, and ELISA were used for exosome
      characterization. RESULTS: Quantification of 45 exosomal miRNAs showed that
      compared with healthy women, 10 miRNAs in the entire cohort of BC patients, 13 in
      the subgroup of 211 HER2-positive BC, and 17 in the subgroup of 224 TNBC were
      significantly deregulated. Plasma levels of 18 exosomal miRNAs differed between
      HER2-positive and TNBC subtypes, and 9 miRNAs of them also differed from healthy
      women. Exosomal miRNAs were significantly associated with the clinicopathological
      and risk factors. In uni- and multivariate models, miR-155 (p = 0.002, p = 0.003,
      respectively) and miR-301 (p = 0.002, p = 0.001, respectively) best predicted
      pathological complete response (pCR). CONCLUSION: Our findings show a network of
      deregulated exosomal miRNAs with specific expression patterns in exosomes of HER2
      positive and TNBC patients that are also associated with clinicopathological
      parameters and pCR within each BC subtype.

PMID- 30301472
TI  - Investigating the growing trend of non-drinking among young people; analysis of
      repeated cross-sectional surveys in England 2005-2015.
AB  - BACKGROUND: Non-drinking among young people has increased over the past decade in
      England, yet the underlying factor driving this change is unknown. Traditionally
      non-drinking has been found to be associated with lower socio-economic status and
      poorer health. This study explores among which sub-groups non-drinking has
      increased, and how this correlates with changes in drinking patterns, to identify
      whether behaviours are becoming more polarised, or reduction is widespread among
      young people. METHODS: Among participants aged 16 to 24 years (N = 9699), within
      the annual cross-sectional nationally-representative Health Survey for England
      2005-2015 datasets, the following analyses were conducted: 1) The proportion of
      non-drinkers among social-demographic and health sub-groups by year, and tests
      for linear trends among sub-groups, adjusting for age were calculated. In pooled
      analyses, an interaction between year and each variable was modelled in sex- and
      age-adjusted logistic regression models on the odds of being a non-drinker versus
      drinker 2) At the population level, spearman correlation co-efficients were
      calculated between the proportion non-drinking and the mean alcohol units
      consumed and binge drinking on the heaviest drinking day, by year. Ordinary least
      squares regression analyses were used, modelling the proportion non-drinking as
      the independent variable, and the mean units/binge drinking as the dependent
      variable. RESULTS: Rates of non-drinking increased from 18% (95%CI 16-22%) in
      2005 to 29% (25-33%) in 2015 (test for trend; p < 0.001), largely attributable to
      increases in lifetime abstention. Not drinking in the past week increased from
      35% (32-39%) to 50% (45-55%) (p < 0.001). Significant linear increases in non
      drinking were found among most sub-groups including healthier sub-groups (non
      smokers, those with high physical activity and good mental health), white
      ethnicity, north and south regions, in full-time education, and employed. No
      significant increases in non-drinking were found among smokers, ethnic minorities
      and those with poor mental health. At the population-level, significant negative
      correlations were found between increases in non-drinking and declines in the
      mean units consumed (rho = - 0.85, p < 0.001), and binge drinking (rho = - 0.87,
      p < 0.001). CONCLUSION: Increases in non-drinking among young people has
      coincided with a delayed initiation into alcohol consumption, and are to be
      welcomed. Future research should explore attitudes towards drinking among young
      people.

PMID- 30301473
TI  - Exercise intervention alters HDL subclass distribution and function in obese
      women.
AB  - BACKGROUND: Obesity is associated with a change in high-density lipoprotein (HDL)
      function and subclass. Exercise training reduces cardiovascular risk in obese
      patients. We aimed to explore the effect of an exercise training stimulus on HDL
      functionality and subclass in obese women. METHODS: Thirty-two obese black South
      African women were randomly assigned to exercise (combined aerobic and resistance
      exercise) or control (no exercise) conditions for 12-weeks. Pre- and post-testing
      included venous blood sampling for analysis of lipid profile and HDL
      functionality, by measuring cellular cholesterol efflux capacity, reduction in
      endothelial vascular cell adhesion molecule (VCAM) expression (anti-inflammatory
      function), paraoxonase (PON) (antioxidative function) and platelet activating
      factor acetylhydrolase (PAF-AH) activities (anti-thrombotic function). PON-1 and
      PAF-AH expression were determined in serum and in isolated HDL using Western
      blotting. Levels of large, intermediate and small HDL subclasses were measured
      using the Lipoprint(r) system. RESULTS: Exercise training resulted in a decrease
      in body mass index (- 1.0 +/- 0.5% vs + 1.2 +/- 0.6%, p = 0.010), PON activity (-
      8.7 +/- 2.4% vs + 1.1 +/- 3.0%, p = 0.021), PAF-AH serum expression (- 22.1 +/-
      8.0% vs + 16.9 +/- 9.8, p = 0.002), and the distribution of small HDL subclasses
      (- 10.1 +/- 5.4% vs + 15.7 +/- 6.6%, p = 0.004) compared to controls. Exercise
      did not alter HDL cellular cholesterol efflux capacity and anti-inflammatory
      function. CONCLUSIONS: These results demonstrate the potential for exercise
      training to modify HDL subclass distribution and HDL function in obese women.
      TRIAL REGISTRATION: Clinical trials number: PACTR201711002789113 .

PMID- 30301475
TI  - Endosuture trainer box simulator as a tool for training and teaching in bariatric
      laparoscopic surgery.
AB  - BACKGROUND: Video surgery requires acquisition of psychomotor skills that are
      different from those required for open surgery. The aim of this study was to
      assess the EndoSuture Trainer Box Simulator (ESTBS), a new bariatric laparoscopic
      skills simulator, as a tool for surgical education, comparing it with a standard
      laparoscopic trainer (SLT). METHODS: A randomized prospective crossover study was
      designed to compare ESTBS versus SLT as a tool for training bariatric
      laparoscopic skills. Participants were assigned to perform a task simulating
      Nissen fundoplication operation. All subjects evaluated the simulators concerning
      to their performance on simulating laparoscopic procedures by the use of a
      questionnaire comparing: triangulation, resistance and resilience, spatial
      perception (stereotaxy), ergonomics and positioning, inverted movements,
      visibility, design, technical and technological resources for training and
      education. The overall score was defined as the median value obtained. A total of
      37 participants were enrolled in the study, including 29 experienced surgeons
      (78.37%) and 08 surgical residents (21.63%). RESULTS: A superior performance was
      observed with ESTBS as compared to SLT upon 7 of the 10 items evaluated in the
      questionnaire. Additionally, the overall score of ESTBS (median of 4, very good)
      was significantly higher (P < 0.0001) than that of SLT (median of 3, good). For
      the items, triangulation, resistance and resilience, ergonomics, design,
      training, technology and teaching, the evaluation for the ESTBS was very good and
      excellent, which was significantly higher than obtained by SLT. Also, ESTBS was
      cheaper. CONCLUSIONS: The ESTBS was shown to present excellent technical and
      technological performances and appears to constitute a useful cost-effective
      promising instrument for teaching and training bariatric surgical laparoscopic
      skills.

PMID- 30301474
TI  - Do medical conditions predispose to the development of chronic back pain? A
      longitudinal co-twin control study of middle-aged males with 11-year follow-up.
AB  - BACKGROUND: Poor general health predicts the transition to chronic back pain
      (CBP), but the role of specific medical conditions in the development of CBP is
      unclear. The study aim was to examine the association of medical conditions with
      the development of CBP ("incident CBP"), while controlling for familial factors,
      including genetics. METHODS: This was a longitudinal co-twin control study
      conducted in a nationwide United States sample from the Vietnam Era Twin
      Registry. The study sample included 3045 males without back problems at baseline,
      including 662 complete twin pairs, who were followed for 11 years. Baseline
      surveys inquired about self-reported medical conditions (arthritis, diabetes,
      hypertension, and coronary artery disease [CAD]). A medical comorbidity score was
      calculated based on the presence and/or treatment of 8 medical conditions.
      Covariates included age, race, and education. At 11-year follow-up, participants
      reported ever having had CBP. Odds ratios (ORs) and 95% confidence intervals (CI)
      were estimated when considering twins as individuals, and in matched-pair co-twin
      control analyses adjusting for familial/genetic factors. RESULTS: Mean age at
      baseline was 51 years and 17% of participants developed CBP over the 11-year
      follow-up. Arthritis was significantly associated with incident CBP in individual
      level analysis (OR 1.8 [95% CI 1.4-2.2]), but not within-pair analysis (OR 0.9
      [95% CI 0.4-1.9]. CAD (OR 1.6 [95% CI 1.0-2.3]), hypertension (OR 1.3 [95% CI 1.0
      1.5]), and the medical comorbidity score (OR 1.2 [95%CI 1.1-2.2]) were
      significantly associated with incident CBP in individual-level analyses;
      associations in within-pair analyses were of comparable magnitude, but not
      statistically significant. Diabetes was not associated with incident CBP.
      CONCLUSIONS: Arthritis, hypertension, CAD, and medical comorbidity score were
      associated with incident CBP in the current study. However, the association
      between arthritis and incident CBP was confounded by familial factors. This
      suggests that prevention or treatment of arthritis is unlikely to be useful for
      CBP prevention. Our findings cannot exclude the possibility of causal
      associations between CAD, hypertension, and medical comorbidities and incident
      CBP.

PMID- 30301476
TI  - Phylogeny and comprehensive revision of mugiliform-infecting myxobolids (Myxozoa,
      Myxobolidae), with the morphological and molecular redescription of the cryptic
      species Myxobolus exiguus.
AB  - Mullets inhabit a wide range of habitats from tropical to temperate regions and
      play a critical role in their ecosystems. This commercially important fish group
      constitutes a significant source of food in several geographic regions, and the
      production of some species for consumption is an increasing trend. About 64
      myxosporean species have been reported in mullets, some of which are cryptic, as
      is the case of Myxobolus exiguus, and M. muelleri. This paper provides, for the
      first time, a detailed and critical revision of the data available for myxobolids
      reported in mullets, determining the species that have bona fide mugiliform fish
      hosts, in accordance with the original species descriptions, the available
      molecular data and the currently accepted taxonomic and phylogenetic criteria.
      Phylogenetic analyses using Bayesian inference and maximum-likelihood
      methodologies suggest that the evolutionary history of myxobolids with bona fide
      mugiliform fish hosts reflects that of its vertebrate hosts, while reinforcing
      known evolutionary factors and old systematic issues of the clade of myxobolids.
      A comprehensive morphological, ultrastructural and molecular redescription is
      also provided for the cryptic species M. exiguus, from infections in the visceral
      peritoneum of the thinlip-grey mullet Chelon ramada in the River Minho, Portugal.

PMID- 30301477
TI  - Psychological distress and psychiatric disorder after natural disasters:
      systematic review and meta-analysis.
AB  - BACKGROUND: Natural disasters are increasing in frequency and severity. They
      cause widespread hardship and are associated with detrimental effects on mental
      health.AimsOur aim is to provide the best estimate of the effects of natural
      disasters on mental health through a systematic review and meta-analysis of the
      rates of psychological distress and psychiatric disorder after natural disasters.
      METHOD: This systematic review and meta-analysis is limited to studies that met
      predetermined quality criteria. We required included studies to make comparisons
      with pre-disaster or non-disaster exposed controls, and sample representative
      populations. Key studies were identified through a comprehensive search of
      PubMed, EMBASE and PsycINFO from 1980 to 3 March 2017. Random effects meta
      analyses were performed for studies that reported key outcomes with appropriate
      statistics. RESULTS: Forty-one studies were identified by the literature search,
      of which 27 contributed to the meta-analyses. Continuous measures of
      psychological distress were increased after natural disasters (combined
      standardised mean difference 0.63, 95% CI 0.27-0.98, P = 0.005). Psychiatric
      disorders were also increased (combined odds ratio 1.84, 95% CI 1.43-2.38, P <
      0.001). Rates of post-traumatic stress disorder and depression were significantly
      increased after disasters. Findings for anxiety and alcohol misuse/dependence
      were not significant. High rates of heterogeneity suggest that disaster-specific
      factors and, to a lesser degree, methodological factors contribute to the
      variance between studies. CONCLUSIONS: Increased rates of psychological distress
      and psychiatric disorders follow natural disasters. High levels of heterogeneity
      between studies suggest that disaster variables and post-disaster response have
      the potential to mitigate adverse effects.Declaration of interestNone.

PMID- 30301478
TI  - Does adding water to a dry starter diet improve calf performance during winter?
AB  - Very recently, we added water to a dry texturized starter diet and found
      substantial improvements in calf performance during summer, leading to the
      hypothesis that the wet starter diet would also benefit calf performance during
      winter. Forty-five 3-day-old male Holstein calves (BW 43.4+/-3.4 kg) were blocked
      by initial BW and distributed randomly to one of three starter diets (1 calf per
      pen; 15 pens per treatment) that differed only in moisture content as 90%, 75%
      and 50% dry matter (DM; DM90, DM75 and DM50, respectively). The starter diet
      comprised 55.1% ground ingredients (soybean meal, barley and corn gluten meal),
      21.9% whole corn, 10% rolled barley and 10% chopped alfalfa hay. The mean ambient
      temperature averaged 2.1+/-0.9 degrees C during the 70-day experiment. Calves
      were weaned at day 50 of the study. Although starter feed intake remained
      unaffected by treatment, the calves receiving DM75 and DM50 consumed more starter
      feed (DM basis) than those receiving DM90 diet during the first 20 days of the
      experiment. Body weight at weaning exhibited a quadratic response with the
      heaviest weaning weight (76.8 kg) occurring when calves consumed DM75 diet.
      Adding water to the dry starter diet tended to linearly increase final BW.
      Average daily gain during the pre- (0.67 kg/day) and post-weaning (1.22 kg/day)
      periods was the greatest for calves receiving DM75 and DM50, respectively.
      Although feed efficiency during the pre-weaning and overall periods did not
      differ across the treatments, a quadratic effect was detected in the post-weaning
      feed efficiency, with the lowest value being observed with DM75 diet. No
      difference was noted on skeletal growth parameters measured on days 50 and 70.
      Adding water to the dry starter diet linearly increased total volatile fatty
      acids concentration in the rumen. No difference among treatments existed in calf
      behavior recorded on days 35 and 70. As moisture content of the starter diet
      increased, the extent of sorting for long particles (>2 mm) and against fine
      particles (<0.125 mm) decreased. During the 70-day winter trial, adding water to
      the dry texturized starter diet with 10% chopped alfalfa hay resulted in a higher
      feed intake during the first weeks of life, a quadratic tendency toward improved
      growth rate during the pre-weaning period, and possibly a more functional rumen
      fermentation. A wet starter diet with 75% DM in the physical form offered in this
      study can be recommended to improve calf performance during winter.

PMID- 30301479
TI  - Effects of feeding treatment on growth rates, metabolic profiles and age at
      puberty, and their relationships in dairy heifers.
AB  - Puberty attainment in dairy heifers has been widely studied from a hormonal point
      of view, but few studies have focussed on puberty-blood profile relationships
      during growth. We led experiments to determine the effects of feeding treatments
      on growth parameters, age at puberty and plasma biochemical profiles, and the
      relationships between age at puberty and metabolic profiles at 6, 9, 12 and 15
      months (mo) of age. Blood samples were collected from 67 Holstein heifers, born
      between September 2011 and February 2012, every 10 days from 5.5 mo of age until
      heifers were considered pubertal (plasma progesterone concentration greater than
      1.0 ng/ml) or oestrus synchronisation (November 2012; 11 to 15 mo of age).
      Heifers born before 30 November were fed either a standard diet (SD, n=27) or an
      intensive-plane diet (ID1, n=27) from 0 to 6 mo of age. This strategy aimed to
      reach 190 to 200 kg (SD) or 220 to 230 kg (ID1) BW at 6 mo of age. All heifers
      born after 1 December received an intensive-plane diet (ID2, n=13) from birth
      until oestrus synchronisation, in order to reach a similar BW at first
      insemination as heifers born before 1 December. Only 56 heifers reached puberty
      before oestrus synchronisation, at an average age of 10.3+/-2.2 mo (6.2 to 14.4
      mo) and a BW of 296+/-40 kg (224 to 369 kg). There was no difference among the
      three feeding treatments until 6 mo, but at 9, 12 and 15 mo of age, ID2 (n=11)
      heifers weighed 37, 52 and 30 kg more than SD (n=22) and ID1 (n=23) heifers
      (P<0.001), respectively. Glucose, non-esterified fatty acids, albumin, aspartate
      aminotransferase, alkaline phosphatase and tartrate-resistant acid phosphatase,
      calcium, phosphorus, potassium and iron decreased with age, whereas beta
      hydroxybutyric acid, total cholesterol, creatinine, the creatinine : albumin
      ratio, alanine aminotransferase and chloride increased. The feeding treatment
      significantly affected creatinine, the creatinine : albumin ratio, and phosphorus
      and sodium levels, which were higher for ID2 heifers compared with SD and ID1. A
      logistic regression based on plasma metabolites at 6 mo of age to explain puberty
      attainment before or at 12 mo of age showed a positive relationship with plasma
      cholesterol (odds ratio=9.05). In conclusion, the feeding treatment had minor
      consequences on plasma metabolites, but it did affect growth performance.

PMID- 30301481
TI  - Population genetic structure and putative migration pathway of Sogatella
      furcifera (Horvath) (Hemiptera, Delphacidae) in Asia.
AB  - The white-backed planthopper, Sogatella furcifera (Horvath) (Hemiptera,
      Delphacidae), has emerged as a serious rice pest in Asia. In the present study,
      12 microsatellite markers were employed to investigate the genetic structure,
      diversity and migration route of 43 populations sampled from seven Asian
      countries (Bangladesh, China, Korea, Laos, Nepal, Thailand, and Vietnam).
      According to the isolation by distance analysis, a significant positive
      correlation was observed between genetic and geographic distances by the Mantel
      test (r2 = 0.4585, P = 0.01), indicating the role of geographic isolation in the
      genetic structure of S. furcifera. A population assignment test using the first
      generation migrants detection method (thresholds a = 0.01) revealed southern
      China and northern Vietnam as the main sources of S. furcifera in Korea. Nepal
      and Bangladesh might be additional potential sources via interconnection with
      Vietnam populations. This paper provides useful data for the migration route and
      origin of S. furcifera in Korea and will contribute to planthopper resistance
      management.

PMID- 30301480
TI  - Experimental combination therapy using low doses of benznidazole and allopurinol
      in mouse models of Trypanosoma cruzi chronic infection.
AB  - This study evaluated the effectiveness of low doses of benznidazole (BNZ) on
      continuous administration (BNZc), combined with allopurinol (ALO), in C57BL/6J
      and C3H/HeN mice infected with Trypanosoma cruzi Nicaragua strain and T. cruzi
      Sylvio-X10/4 clone. TcN-C57BL/6J was also treated with intermittent doses of BNZ
      (BNZit). The drug therapy started 3 months post infection (pi) in the chronic
      phase of mice with heart disease progression, followed-up at 6 months pi. TcN
      C57BL/6J treated with BNZc was also monitored up to 12 months pi by serology and
      electrocardiogram. These mice showed severe electrical abnormalities, which were
      not observed after BNZc or BNZit. ALO only showed positive interaction with the
      lowest dose of BNZ. A clear parasitic effect, with significant reductions in
      antibody titres and parasitic loads, was achieved in all models with low doses of
      BNZ, and a 25% reduction of the conventional dose showed more efficacy to inhibit
      the development of the pathology. However, BNZ 75 showed partial efficacy in the
      TcSylvio-X10/4-C3H/HeN model. In our experimental designs, C57BL/6J allowed to
      clearly define a chronic phase, and through reproducible efficacy indicators, it
      can be considered a good preclinical model.

PMID- 30301482
TI  - Parasite and host biomass and reproductive output in barnacle populations in the
      rocky intertidal zone.
AB  - The rocky intertidal zone has a long history of ecological study with barnacles
      frequently serving as a model system to explore foundational theories. Parasites
      are often ignored in community ecology studies, and this particularly holds for
      true for the rocky intertidal zone. We explore the role of the isopod parasite,
      Hemioniscus balani, on its host, the acorn barnacle, Chthamalus fissus. We use
      the currencies of biomass and reproduction measured at the individual level, then
      applied to the population level, to evaluate the importance of this parasite to
      barnacle populations. We found H. balani can comprise substantial biomass in
      'apparent' barnacle populations, sometimes even equaling barnacle biomass.
      Additionally, parasite reproduction sometimes matched barnacle reproduction.
      Thus, parasites divert substantial energy flow from the barnacle population and
      to near-shore communities in the form of parasite larvae. Parasites appeared to
      decrease barnacle reproduction per area. Potentially, this parasite may control
      barnacle populations, depending on the extent to which heavily infected barnacle
      populations contribute to barnacle populations at larger scales. These findings
      regarding the importance of a particular parasite for host population dynamics in
      this well studied ecosystem call for the integration of disease dynamics into
      community ecological studies of the rocky intertidal zone.

PMID- 30301483
TI  - A tale of three kingdoms: members of the Phylum Nematoda independently acquired
      the detoxifying enzyme cyanase through horizontal gene transfer from plants and
      bacteria.
AB  - Horizontal gene transfer (HGT) has played an important role in the evolution of
      nematodes. Among candidate genes, cyanase, which is typically found only in
      plants, bacteria and fungi, is present in more than 35 members of the Phylum
      Nematoda, but absent from free-living and clade V organisms. Phylogenetic
      analyses showed that the cyanases of clade I organisms Trichinella spp.,
      Trichuris spp. and Soboliphyme baturini (Subclass: Dorylaimia) represent a well
      supported monophyletic clade with plant cyanases. In contrast, all cyanases found
      within the Subclass Chromadoria which encompasses filarioids, ascaridoids and
      strongyloids are homologous to those of bacteria. Western blots exhibited typical
      multimeric forms of the native molecule in protein extracts of Trichinella
      spiralis muscle larvae, where immunohistochemical staining localized the protein
      to the worm hypodermis and underlying muscle. Recombinant Trichinella cyanase was
      bioactive where gene transcription profiles support functional activity in vivo.
      Results suggest that: (1) independent HGT in parasitic nematodes originated from
      different Kingdoms; (2) cyanase acquired an active role in the biology of extant
      Trichinella; (3) acquisition occurred more than 400 million years ago (MYA),
      prior to the divergence of the Trichinellida and Dioctophymatida, and (4) early,
      free-living ancestors of the genus Trichinella had an association with
      terrestrial plants.

PMID- 30301484
TI  - Effects of resveratrol and genistein on growth, nutrient utilization and fatty
      acid composition of rainbow trout.
AB  - The replacement of the finite and costly resource fish oil is an important task
      for aquaculture nutrition. A promising approach could be the use of plant
      bioactives that may have the potential to influence the metabolism and the
      synthesis of n-3 long chain polyunsaturated fatty acids, especially EPA (20:5n-3)
      and DHA (22:6n-3). In this study, the two phytochemicals resveratrol (RV) and
      genistein (G) were investigated for their effects on fish growth, nutrient
      utilization and body nutrient composition alongside their effects on whole body
      fatty acid (FA) composition. In a feeding trial lasting 8 weeks, rainbow trout
      (initial BW: 81.4+/-0.5 g) were held in a recirculating aquaculture system and
      fed six experimental diets with varying fish oil levels as plain variants or
      supplemented with 0.3% of dry matter (DM) of either RV or G. The six diets were
      as follows: diet F4 had 4% DM fish oil, diet F0 had 0% DM fish oil, diets F4+RV,
      F4+G, F0+RV and F0+G were equal to the diets F4 and F0, respectively, and
      supplemented with the phytochemicals RV and G. The feeding of the F0+RV diet
      resulted in reduced feed intake, growth rate and slightly reduced whole body
      lipid levels. At the same time, the amount of polyunsaturated FA and the n-3/n-6
      ratio were significantly increased in whole body homogenates of rainbow trout fed
      diet F0+RV in comparison to the F0 control. The feeding of the F0+G diet led to
      reduced feed intake, slightly increased protein utilization but did not
      significantly affect the whole body FA composition. Overall, feeding the fish oil
      free diet supplemented with the phytochemicals resulted in more pronounced
      effects on fish performance and FA composition than the single factors per se
      (dietary fish oil level or phytochemical). Present data indicate that G might not
      be of profitable use for trout nutrition. In terms of FA composition, RV could be
      a potentially useful complement for fish oil. However, the impairment of growth
      and performance parameters as observed in the present study discourages its use
      in trout diets.

PMID- 30301486
TI  - Understanding Urban Stormwater Denitrification in Bioretention Internal Water
      Storage Zones.

PMID- 30301485
TI  - Operational experience with a full-scale Anaerobic Baffled Reactor treating
      municipal wastewater.
AB  - The aim of the study was to investigate the influence of moderate temperatures on
      the efficiency of a full-scale anaerobic treatment system consisting of a primary
      sedimentation unit (PST) and an Anaerobic Baffled Reactor (ABR, approx. 10 m3).
      Therefore, two trials with different test setups in series were carried out (1st
      trial: continuous load, 2nd trial: diurnal variated load). The plant was fed with
      municipal wastewater and operated at temperatures between 8 and 24  degrees C.
      The mean efficiency of the ABR was low, compared to the one of the PST. At 10 
      degrees C, only 10 % of the COD was removed. The COD removal efficiency of the
      plant (PST + ABR) averaged 50 %. At low temperatures, volatile fatty acids began
      to accumulate. In both trials, the contents of total suspended solids in the
      sludge bed differed distinctly and influenced the effort for desludging.

PMID- 30301487
TI  - A novel method for oxidative degradation of metanil yellow azo dye by
      hexacynoferrate(III) ions.
AB  - In the present work the degradation of metanil yellow an azo dye by
      hexacyanoferrate(III) ions (oxidant) in the aqueous alkaline medium has been
      investigated by kinetic - spectrophotometric method at lambdamax 435 nm of the
      reaction mixture. The effect of various parameters such as the concentration of
      dye, oxidant and solution pH on the reaction rate has been determined. The
      results show that the rate of degradation increases linearly with the increase in
      concentrations of oxidant and dye at optimum pH 9.0 and constant temperature of
      40 +/- 0.1 degrees C. Thermodynamic parameters like energy of activation,
      enthalpy of activation, entropy of activation and energy of formation have been
      calculated by studying the reaction rate at four different temperatures, i.e. 40 
      55 0C. Based on the experimental results, a plausible reaction mechanism
      involving complex formation has been proposed and a rate law has been derived. UV
      Vis and LC-MS methods of analysis of degradation products show the formation of
      simpler and less hazardous degradation products.

PMID- 30301488
TI  - Surveillance on speed: Being aware of infectious diseases in migrants mass
      accommodations - an easy and flexible toolkit for field application of syndromic
      surveillance, Germany, 2016 to 2017.
AB  - Europe received an increased number of migrants in 2015. Housing in inadequate
      mass accommodations (MA) made migrants prone to infectious disease outbreaks. In
      order to enhance awareness for infectious diseases (ID) and to detect clusters
      early, we developed and evaluated a syndromic surveillance system in three MA
      with medical centres in Berlin, Germany. Healthcare workers transferred daily
      data on 14 syndromes to the German public health institute (Robert Koch
      Institute). Clusters of ID syndromes and single cases of outbreak-prone diseases
      produced a signal according to a simple aberration-detection algorithm that
      computes a statistical threshold above which a case count is considered unusually
      high. Between May 2016-April 2017, 9,364 syndromes were reported; 2,717 (29%)
      were ID, of those 2,017 (74%) were respiratory infections, 262 (10%) skin
      parasites, 181 (7%) gastrointestinal infections. The system produced 204 signals,
      no major outbreak was detected. The surveillance reinforced awareness for public
      health aspects of ID. It provided real-time data on migrants' health and stressed
      the burden of non-communicable diseases. The tool is available online and was
      evaluated as being feasible and flexible. It complements traditional notification
      systems. We recommend its usage especially when laboratory testing is not
      available and real-time data are needed.

PMID- 30301490
TI  - Addendum for Euro Surveill. 2018;23(15).

PMID- 30301489
TI  - Summary of available surveillance data on hepatitis C virus infection from eight
      Arctic countries, 2012 to 2014.
AB  - We summarised available hepatitis C virus (HCV) surveillance data for 2012-14
      from Arctic/sub-Arctic countries/regions. We sent a HCV data collection template
      by email to public health authorities in all jurisdictions. Population statistics
      obtained from census sources for each country were used to estimate rates of
      reported acute and chronic/undifferentiated HCV cases. Seven countries with
      Arctic regions (Canada, Denmark, Finland, Greenland, Norway, Sweden and the
      United States, represented by the state of Alaska), including three Canadian
      territories and one province, as well as 11 Russian subnational Arctic regions,
      completed the data collection template. Data on acute HCV infection during 2014
      was available from three Arctic countries and all Russian Arctic regions (rate
      range 0/100,000 population in Greenland, as well as Nenets and Chukotka Automous
      Okrugs (Russian subnational Arctic regions) to 3.7/100,000 in the Russian
      Republic of Komi). The rate of people with chronic/undifferentiated HCV infection
      in 2014 ranged from 0/100,000 in Greenland to 171.2/100,000 in Alaska. In most
      countries/regions, the majority of HCV-infected people were male and aged 19-64
      years. Differences in surveillance methods preclude direct comparisons of HCV
      surveillance data between Arctic countries/regions. Our data can inform future
      efforts to develop standardised approaches to HCV surveillance in the Arctic
      countries/regions by identifying similarities/differences between the
      surveillance data collected.

PMID- 30301491
TI  - Authors' correction for Euro Surveill. 2018;23(28).

PMID- 30301493
TI  - Effect of hydatid cyst antigens on inhibition of melanoma cancer growth in mouse
      model.
AB  - Cancer is the main cause of death in the developed countries. There are some
      scientific evidences indicating that parasitic infections induce antitumor
      activity against certain types of cancers. Hydatid cyst is the larval stage of
      Echinococcus granulosus, which causes hydatidosis in human and livestock. We have
      already shown that vaccination of mice with hydatid cyst crude antigens and
      subsequently challenge them with cancer cells, causes inhibition of melanoma
      cancer growth. In this study, therapeutic effects of hydatid cyst antigens on
      C57/black mice that had already been challenged with melanoma tumor were
      investigated. In this experimental study, 6 groups of C57 black mice were
      subcutaneously inoculated with melanoma cancer cells (line B16F10) in PBS inside
      their chest site. After 2 weeks case groups were injected with hydatid cyst
      fluid, a fraction of cyst fluid, live protoscolices or BCG.  control groups were
      injected with alum alone and other control group was left intact without any
      intervention. The size of each tumor was measured in all mice. Blood samples were
      also taken to estimate Interleukin-2 (IL-2), Tumor necrosis factor alpha (TNF
      alpha), Interferon gamma (IFN-gamma) and Interleukin-4 (IL-4) levels. Treatment
      of mice bearing melanoma cancer with hydatid cyst antigens resulted in inhibition
      of tumor growth and the difference between mean size of tumor in case and control
      groups was statistically significant. Also, according to our results mean level
      of measured cytokines between case and control groups was statistically
      different. Hydatid cyst antigens have anti-melanoma activities and this effect
      may be related to immune response to parasite antigens.

PMID- 30301495
TI  - Boric acid protects against cyclophosphamide-induced oxidative stress and renal
      damage in rats.
AB  - The worldwide increase in the rate of cancer incidence also leads to a
      significant increase in the use of chemotherapeutic agents. Unfortunately, the
      optimal clinical usefulness of these agents is heavy restricted by a high
      incidence of several organ toxicity and as well reason oxidative stress and bring
      about changing in antioxidant status. Kidney toxicity is a side effect often
      encountered with cyclophosphamide (CPM) which is commonly used in most cancer
      chemotherapy. The present study aims on the assessment of the probable defensive
      efficacy of Boric acid (BA) against CPM-induced oxidative stress and renal damage
      in rats. Based upon our investigation results with oxidative stress markers and
      light microscopic findings, it can be concluded that BA significantly reduced CPM
      induced oxidative stress and renal damage. As far as we know, high dose (200
      mg/kg) of BA are the first study on the prevention of kidney damage caused by
      CPM. It is thought that the renoprotective effects of BA may be due to an
      increase in the activity of the antioxidant protection system and also inhibition
      of lipid per oxidation.

PMID- 30301492
TI  - Screening for neurocysticercosis in internationally adopted children: yield, cost
      and performance of serological tests, Italy, 2001 to 2016.
AB  - IntroductionNeurocysticercosis (NCC) is one of the leading causes of epilepsy
      worldwide. The majority of cases in Europe are diagnosed in immigrants. Currently
      in Italy, routine serological screening for cysticercosis is recommended for
      internationally adopted children (IAC) coming from endemic countries. Methods: We
      retrospectively analyse the results of the serological screening for
      cysticercosis in IAC 16 years old or younger, attending two Italian third level
      paediatric clinics in 2001-16. Results: Of 2,973 children included in the study,
      2,437 (82.0%) were screened by enzyme-linked immune electro transfer blot (EITB),
      1,534 (51.6%) by ELISA, and 998 (33.6%) by both tests. The seroprevalence of
      cysticercosis ranged between 1.7% and 8.9% according to EITB and ELISA,
      respectively. Overall, 13 children were diagnosed with NCC accounting for a NCC
      frequency of 0.4% (95% confidence interval (CI): 0.2-0.6%). Among the 168
      seropositive children, only seven (4.2%) were diagnosed with NCC. Of these
      children, three were asymptomatic and four presented epilepsy. Among seronegative
      children (n = 2,805), seven presented with neurological symptoms that lead to the
      diagnosis of NCC in six cases. The sensitivity, specificity, positive and
      negative predictive value for the diagnosis of NCC were 54.5%, 98.6%, 14.6%,
      99.8% for EITB and 22.2%, 91.1%, 1.4%, 99.5% for ELISA. The yield of the
      screening programme was 437 NCC cases per 100,000. The number needed to screen to
      detect one NCC case was 228. The cost per NCC case detected was EUR 10,372.
      Conclusion: On the base of our findings we suggest the ongoing serological
      screening for cysticercosis to be discontinued, at least in Italy, until further
      evidence in support will be available.

PMID- 30301494
TI  - Establishment of a cochlear injury model using bone-conducted ultrasound
      irradiation in guinea pigs and investigation on peripheral coding and recognition
      of ultrasonic signals.
AB  - The cochlea of guinea pigs was irradiated with different frequencies of bone
      conducted ultrasound (BCU) at a specific dose to induce cochlear hair cell
      specific injuries, in order to establish frequency-related cochlear hair cell
      specific injury models. Cochlear near-field potentials were then evoked using BCU
      of different frequencies and intensities to explore the peripheral coding and
      recognition of BCU by the cochlea. The inner ears of guinea pigs were irradiated
      by 30 kHz at 100 db and 80 kHz at100 db BCU for 6h to create frequency-related,
      ultrasound-specific cochlear injury models. Then, 30 kHz and 80 kHz BCU of
      different intensities were used to evoke auditory brainstem response (ABR)
      thresholds, compound action potential (CAP) thresholds, and action potential (AP)
      intensity-amplitude input-output curves in the normal control group and the
      ultrasonic cochlear injury group. This allowed us to explore the coding and
      recognition of BCU frequencies and intensities by cochlear hair cells.
      Immunofluorescence assay of outer hair cell (OHC) Prestin and inner hair cell
      (IHC) Otofelin was performed to verify the injury models. Irradiation of guinea
      pig inner ears by 30 kHz and 80 kHz BCU at a specific dose induced hair cell
      injuries at different sites. Irradiation with low frequency BCU mainly induced
      OHC injury, whereas irradiation with high frequency BCU induced IHC injury;
      moreover, IHC injury was more serious than OHC injury. The 30 kHz-evoked ABR
      threshold was significantly higher in the 30 kHz ultrasonic cochlear injury group
      compared to the normal control group. The 30 kHz-evoked ABR threshold was
      significantly higher in the 30 kHz ultrasonic cochlear injury group compared to
      the 80 kHz ultrasonic cochlear injury group. The difference in the 80 kHz-evoked
      ABR thresholds were not significant between the 30 kHz and 80 kHz ultrasonic
      cochlear injury groups. The click- and 30 kHz-evoked AP intensity-amplitude
      curves for the 30 kHz ultrasonic cochlear injury group indicate that the AP
      amplitude evoked at the same intensity was higher in the 30 kHz-evoked group than
      the click-evoked group. The spatial positions of cochlear hair cells in guinea
      pigs had a coding function for the frequencies of low-frequency ultrasound. OHCs
      have an amplification effect on the coding of low-frequency ultrasonic
      intensities. The peripheral perception of high frequency BCU may not require the
      participation of cochlear hair cells.

PMID- 30301496
TI  - Keratinocytes contribute to the recruitment and M1 polarisation of macrophages
      during C. albicans colonisation.
AB  - Candida albicans (C. albicans) is an opportunistic human fungal pathogen that
      colonises the skin. Both keratinocytes and macrophages play crucial roles in host
      defence against C. albicans. However, the interaction of keratinocytes with
      macrophages during C. albicans colonisation has not been well studied. In this
      study, macrophages were cultured in conditioned medium from keratinocytes treated
      with heat-inactivated C. albicans (CM-C. albicans), macrophage migration and
      polarised activation and were then assessed by a Transwell assay, flow cytometry,
      quantitative real-time PCR (qPCR), Western blot and an enzyme-linked
      immunosorbent assay (ELISA). The results showed that CM-C. albicans-stimulated
      macrophages display significantly increased migration and phagocytosis, and they
      display an upregulation of proinflammatory cytokines (tumour necrosis factor
      alpha (TNF-a), interleukin (IL)-12 and nitric oxide (NO)). Markers characteristic
      of M1 macrophages, such as human leukocyte antigen (HLA)-DR, CD86 and inducible
      nitric oxide synthase (iNOS), are upregulated, whereas markers of M2 macrophages,
      such as mannose receptor (MR) and Arginase 1 (Arg1), are not affected.
      Additionally, the levels of TNF-a, IL-12 and monocyte chemotactic protein 1 (MCP
      1) in CM-C. albicans are markedly upregulated, whereas the levels of IL-4 and IL
      10 are not affected. And the CM-C. albicans-induced M1 macrophage polarisation,
      proinflammatory cytokine production and phagocytosis could be blocked by an anti
      TNF-a neutralising antibody. This study showed that keratinocytes may promote
      macrophage recruitment and M1 polarisation during C. albicans colonisation at
      least in part by secreting TNF-a.

PMID- 30301497
TI  - A simplified and optimized protocol for total DNA extraction from insect species:
      applicable for studying genetic diversity and PCR-based specimen identification
      via partial amplification of cytochrome oxidase I (COI) gene.
AB  - The efficient DNA extraction from insects has been suggested as a critical and
      main step affecting molecular entomology for taxonomic identification, the
      establishment of DNA barcoding library and analysis of genetic diversity
      relationship between insect populations. For successfully apply these molecular
      techniques, high-quantity and high-quality of the extracted DNA are required.
      Several protocols for efficient genomic DNA extraction from insects have been
      developed. In this research, we represent a rapid, reliable and cost-effective
      method that it is not reliant on poisonous and enzymatic reagents for DNA
      extraction from insect tissues. Results showed that high quantity and high
      quality of the isolated DNA by this method is suitable and can be used directly
      for PCR, also is enough to do hundreds of molecular reactions. In conclusion, we
      described a fast, cost-effective, non-toxic and enzyme-free protocol for high
      yield genomic DNA extraction from green Lacewings (Chrysoperla carnea) tissues in
      basic equipment laboratories.

PMID- 30301498
TI  - Investigation on the expression stability of common reference genes in Aurelia
      sp.1 under hypoxia.
AB  - RT-qPCR (Quantitative real-time polymerase chain reaction) is a reliable
      molecular biology technique used for gene expression detection due to its high
      sensibility and good reproducibility. However, suitable reference genes for RT
      qPCR are often not available to investigate the expression of target genes in
      jellyfish under different conditions. To determine the responsible genes of
      jellyfish under hypoxia, primers to amplify the actin gene was designed for the
      amplification according to the conserved actin amino acid sequences of cnidarian.
      Then, we cloned and sequenced the partial cDNA sequence of beta-actin gene
      containing 849 bp nucleic acids was cloned and sequenced, and the four common
      housekeeping genes (18S rRNA, beta-actin, alpha-tubulin and GAPDH) were detected.
      To obtain suitable reference genes, we compared the four genes under normoxia and
      hypoxia were determined and compared using RT-qPCR. The evaluation result shows
      that alpha-tubulin gene can be used as single reference gene, and alpha-tubulin
      and beta-actin can be served as multiple reference genes to study relative gene
      expression related to hypoxic tolerance of Aurelia sp.1. This research will
      establish foundation to reveal the molecular mechanism of jellyfish under
      hypoxia.

PMID- 30301499
TI  - Hydrothermal synthesis of highly fluorescent and non-toxic carbon dots using
      Stevia rebaudiana Bertoni.
AB  - Herein, green, environmental-friendly and economical synthesize of luminescent
      carbon dots (CDs) was reported using the plant-based material, Stevia rebaudiana
      Bertoni, as a herbal bio-sweetener. In this regard, hydrothermal carbonization of
      Stevia was performed under mild conditions and without any chemical oxidizing
      agents. Exploring the morphological aspect, surface groups, chemical composition
      and structure of Stevia-based CDs have been carried out systematically using SEM
      EDS, TEM, fluorescence, FT-IR, UV-Vis, and XRD techniques. UV-Vis spectra
      displayed signature absorption of CDs at 240 nm related to the pi-pi* transitions
      of C=C. Fluorescence spectra showed characteristic emission at the peak
      wavelength of 431 nm with a quantum yield of approximately 17.5%. Moreover, there
      was no living cell cytotoxicity for the as-prepared CDs confirmed by confocal
      microscopy. These results indicated that these plant-based CDs are ideal non
      toxic promising markers for cellular bio-imaging.

PMID- 30301500
TI  - NET-1 promotes invasion, adhesion and growth of hepatocellular carcinoma by
      regulating the expression of BAX, caspase 3, caspase 8 and BCL2.
AB  - Dysregulation of neuroepithelial transforming gene-1 (NET-1) has been shown in
      hepatocellular carcinoma (HCC) patients. We aimed to evaluate the influence of
      NET-1 on HCC invasion, adhesion and growth. In vitro cellular functional assays
      including invasion and adhesion were performed to evaluate the effects of
      knockdown and overexpression of NET-1. HCC cells were transplanted into nude
      mice, and tumor growth was assessed. BAX, caspase 3, caspase 8 and BCL2 protein
      levels were detected by western blot. After transfection with NET-1 siRNA, NET-1
      positive ratio in HCC cells significantly decreased. Cell invasion and adhesion
      assay showed that knockdown of NET-1 reduced the invasion and adhesion ability of
      HCC cells, whereas overexpression of NET-1 increased the ability. The evaluation
      of tumor growth revealed that NET-1 knockdown significantly decreased tumor
      volume and weight, while NET-1 overexpression promoted tumor growth in nude mice.
      Western blot showed that NET-1 knockdown increased BAX, caspase 3 and caspase 8
      expression but decreased BCL2 expression, whereas NET-1 overexpression
      significantly down-regulated BAX, caspase 3 and caspase 8 expression but
      increased BCL2 expression. Our data suggest that NET-1 promotes HCC invasion,
      adhesion and growth by regulating BAX, caspase 3, caspase 8 and BCL2 expression.

PMID- 30301501
TI  - Screening of total phenolic, antiradical and antioxidant activities of
      Wiedemannia orientalis.
AB  - In this study, it was aimed to investigate total phenolic, antioxidant and
      antiradical activities of water and ethanolic extracts of the Wiedemannia
      orientalis (W. orientalis). In order to investigate the antiradical capacities,
      DPPH and ABTS radical scavenging activates were employed in the evaluation
      process. For the evaluation of antioxidant capacities, activities of
      phosphomolybdenum assay, reducing power and metal chelating were investigated. 
      In the evaluations, the amounts of total phenolics were determined to be 11.95+/
      0.02-17.27+/-0.09 mg Gallic acid equivalents (GAE)/g in W. orientalis extracts,
      respectively. Additionally, the amount of reducing power and total antioxidant
      capacity of leaf ethanol extract of W. orientalis were determined to be higher
      compared to the other extracts of W. orientalis. While the highest activity was
      observed in flower ethanol extract on the DPPH radical scavenging activity,
      flower water extract demonstrated better results in metal chelating activity. In
      the ABTS radical chelating activity, no significant differences were observed. As
      a result, it was suggested in our study that extracts of W. orientalis could be
      regarded as a natural and alternative source in pharmacology and medicine and
      food sectors. Such results can be put to use in pharmaceutical formulations and
      may lead to the developments of new human drugs from this medicinal plant.

PMID- 30301502
TI  - Vitamin D can be used as a supplement against cancer stem cells.
AB  - Cancer is standing like a bottomless pit or a black hole in front of mankind.
      Scientists are trying all possible ways to find a solution against to cancer. As
      known, cancer is a phenomenon fed from internal dynamics. One of internal dynamic
      is cancer stem cells that are involved in the formation and development of
      cancer. Because of these dynamics, scientists began to search solution inside of
      the body. Another internal dynamic is vitamin D and it is not only important in
      calcium homeostasis but also it is important for cell proliferation,
      differentiation, and apoptosis. In this study, we investigated the effect of
      vitamin D on cancer stem cells that sorted from MCF-7 cell line and on HEK293
      cell line as control. Our results showed that calcitriol treatment reduced the
      number of CSC (Cancer Stem Cell) in the MCF-7 cell while increased in HEK293 cell
      population. Gene expression analyses showed that effect of calcitriol on
      apoptosis plays an important role in this reduction. Deficiency or unavailability
      of vitamin D may take a role in the pathogenesis of breast cancer.

PMID- 30301504
TI  - Effects of melatonin on apoptosis and cell differentiation in MCF-7 derived
      cancer stem cells.
AB  - Melatonin is a hormone of the pineal gland that has a wide range of biological
      effects such as antioxidant, anti-inflammatory, and anti-tumor activity. Previous
      studies have shown that melatonin also affects survival, proliferation, and
      apoptosis of the cells. In this study, we investigated the effect of melatonin on
      apoptosis, self-renewal, and differentiation. For this purpose, MCF-7 and HEK293
      cells were subjected to melatonin treatment. Expression of genes related to
      apoptosis (Bax and Bcl2) and self-renewal and differentiation (Oct4, Sox2, and
      Nanog) analyzed after the sorting of cancer stem cells from MCF-7 cells. Results
      showed that the effect of melatonin is dependent on the melatonin concentration
      and treatment periods. Melatonin treatment decreased the cell proliferation rate
      of MCF-7 in contrast to HEK293. Also, this treatment increased apoptosis in MCF-7
      cells and decreased in HEK293 cells. Gene expression of Nanog was decreased and
      Sox2 was increased in both cell groups after the melatonin treatment. Expression
      of Oct4 was decreased in MCF-7 cells and increased in HEK293 cells. We determined
      that melatonin decreases apoptosis and differentiation of stem cells in normal
      HEK293 stem cells, but increases apoptosis and differentiation in the MCF-7
      cancer stem cells.

PMID- 30301503
TI  - Serum levels of IL-31, IL-33 and ST2 in allergic rhinitis of children in China.
AB  - This study aimed to compare the serum levels of IL-31, IL-33 and ST2 in children
      patients with allergic rhinitis (AR) and allergic asthma and tried to reveal more
      insights in development of AR. Thirty-six children patients with intermittent AR
      were selected in the present study during January 2013 to December 2016. Two
      control groups were set, the allergic asthma group and the healthy individuals.
      Atopic status of all participants in this study was tested and confirmed by skin
      prick testing (SPT). Levels of IL-31, IL-33 and ST2 were determined using ELISA.
      Statistical analysis was performed by SPSS 18.0. There is no significant
      difference in age, gender ratio and BMI for all patients. However, positive ratio
      of SPT and total IgE in patients' groups were significantly higher than the
      control group. Levels of IL-33 and IL-31 in both AR and allergic asthma group
      were significantly higher than those of the control group, P<0.05. However, level
      of ST2 in the three groups didn't show significant difference. Correlation
      analysis showed that there was a positive correlation between levels of IL-33 and
      IL-31, P<0.05. However, levels of ST2 and IL-33, ST2 and IL-31 were not
      significantly correlated. The serum levels of IL-33 and IL-31 were significantly
      up-regulated in both AR and allergic asthma patients compared with normal
      individuals. These results could provide more clinical evidences for
      understanding roles of IL-33, IL-31 and ST2 in children patients with allergic
      rhinitis.

PMID- 30301505
TI  - Effect of cobalt nanoparticles and cobalt ions on alkaloids production and
      expression of CrMPK3 gene in Catharanthus roseus suspension cultures.
AB  - The capabilities of cobalt ions (Co2+) and cobalt nanoparticles (CoNPs) in
      enhancing alkaloids accumulation in Catharanthus roseus suspension cultures were
      evaluated in relation to the expression of CrMPK3 gene. Four concentrations (5,
      10, 15 and 20 mg/L) of each cobalt form were utilized in addition to control.
      Both forms induced oxidative stress that was more pronounced for Co2+ treatments.
      A positive correlation was observed between cobalt concentration and expression
      of CrMPK3 gene. However, a characteristic temporal expression profile was
      recorded for each cobalt form. Also, positive correlations were detected between
      both cobalt concentration and expression of CrMPK3 gene on one hand and the
      activities of antioxidant enzymes (SOD and APX) and alkaloids content on the
      other hand. Such correlations suggest CrMPK3 gene as a common player in cobalt
      induced stress signaling; regardless of cobalt form. Results revealed the higher
      capability of Co2+, compared with CoNPs, in enhancing alkaloids accumulation.
      However, results supported CoNPs as a novel tool in manipulating cobalt-induced
      alkaloids production in C. roseus.

PMID- 30301506
TI  - SMAR1 promotes immune escape of Tri-negative Breast Cancer through a mechanism
      involving T-bet/PD-1 Axis.
AB  - This study was aimed at investigating the specific molecular mechanisms involved
      in the regulation of immune escape of triple-negative breast cancer (TNBC) by
      SMRI, so as to provide a new clinical treatment target for the disease. Mouse
      original 4T1 breast cancer cells were inoculated subcutaneously in BALB/C to
      establish TNBC mouse model. CD8+T cells with immunological effects were selected
      from mouse thymus glands for primary culture. The CD8+positive T cells were
      infected with lentivirus interference vectors, and the proliferation of CD8+ T
      cells were determined by trypan blue staining and flow cytometry. CD8+T cells and
      4T1 cells were cultured together so as to determine the cytotoxic effects of
      SMAR1-downregulated CD8+ T cells on tumor cells and the expression of cytokines
      (IFN-gamma, TNF-alpha, IL-2, IL-4 and IL-6). The expressions of SMAR1, T-bet and
      PD-1 were assayed by Western blot. SMAR1-downregulated CD8+T cells were injected
      into 4T1 tumor-bearing mice through the caudal vein, and the growth of tumor in
      mice was monitored. Following the infection of CD8+T cells with SMAR1
      downregulated lentiviral system, cell apoptosis level was decreased significantly
      (control vs. sh-SMAR1: 32.23 +/- 12.4 % vs. 18.28 +/- 8.93 %, p < 0.05). Results
      from trypan blue staining experiments showed that the proliferation of CD8+ T
      cells in the SMAR1-downregulated group was significantly increased; SMAR1
      downregulated CD8+ T cells promoted the production of IFN-gamma, TNF-alpha, IL-2,
      IL-4 and IL-6 in 4T1 breast cancer cells (p < 0.05). Western blot showed that
      SMAR1 down-regulation led to significant upregulation of T-bet, while PD-1 was
      downregulated, when compared to the control group (p < 0.05). The downregulation
      of SMAR1 was associated with significant reduction in tumor size in mice (p <
      0.05). SMAR1 downregulation enhances the tumor killing effect of CD8+T cells by
      activating T-bet and down-regulating PD-1.

PMID- 30301507
TI  - Characterization of antioxidant activity of sulfur compounds in black garlic.
AB  - Different types of sulfur compounds, namely S-allyl-L-cysteine (SAC), S-allyl-L
      cysteine sulfoxide (ACSO) and a synthetic gamma-L-glutamyl-S-allyl-L-cysteine
      (GSAC) were extracted from black garlic and their inhibition to the advanced
      glycation end-products (AGEs) were investigated. Upon addition of inhibitor, the
      amount of produced fructosamine was determined by UV visible spectroscopy. The
      change of pentosidine and fluorescent AGEs during reaction was detected by
      fluorescence method and the change of carboxymethyl lysine (CML) was detected by
      high performance liquid chromatography. It was found that the inhibitory effects
      of SAC and ACSO are stronger to the early and mid non-fluorescent products in
      glycosylation reaction, and GSAC has an obvious inhibitory effect on the later
      reaction products. All these three inhibitors can effectively inhibit advanced
      glycation reaction. Although their effects on glycation products are different
      due to different chemical structures, they have similar inhibitory effects on
      fluorescent products.

PMID- 30301508
TI  - Omentin Val/Val genotype increases predisposition to acne vulgaris without
      changing omentin serum level.
AB  - Acne vulgaris is the most frequent and multifactorial inflammatory skin disorder
      in all races. Obesity is considered to be a risk factor for acne due to its
      contribution to inflammation. The involvements of inflammatory (leptin and
      resistin) and anti-inflammatory (adiponectin) adipokines in the pathogenesis of
      acne were reported. Omentin resembles adiponectin in terms of having inhibitory
      effect on tumor necrosis factor-alpha (TNF-alpha) induced inflammation, a vital
      process in the acne formation. This study was designed to investigate the
      putative involvement of omentin in acne formation. The genotyping was performed
      by restriction fragment length polymorphism (RFLP) method. Serum omentin protein
      levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Serum omentin
      level was not significantly changed between groups. However, the decreased serum
      omentin level was observed as the mean value of BMI increased. The Asp/Asp,
      Val/Asp and Val/Val genotypes distributions for control and patient groups
      (19[17.4%], 22[20.2%], and 3[2.8%] respectively, vs. 31[28.4%], 25[22.9%], and
      9[8.3%], respectively) were obtained. The Val/Val (mutant homozygote) genotype
      was found nearly 1.8 times more in the patient group (p=0.403, OR=1.839 (0.442
      7.653)). This is the first time to clarify a linkage between anti-inflammatory
      omentin and acne vulgaris. Omentin Val109Asp polymorphism affects the overall
      function of the protein. In conclusion, omentin Val/Val (mutant homozygote)
      genotype increases predisposition to acne vulgaris by probably disrupting overall
      protein function of omentin.

PMID- 30301509
TI  - Roscovitine and Trichostatin A promote DNA damage repair during porcine oocyte
      maturation.
AB  - Faithful repair of DNA double-strand breaks in mammalian oocytes is essential for
      meiotic maturation and embryonic development. In the present study we
      investigated the roles of Roscovitine and Trichostatin A (TSA) in DNA damage
      recovery during in vitro maturation of porcine oocytes. Etoposide was used to
      trigger DNA damage in oocytes. When these DNA-damaged oocytes were treated with 2
      MUM Roscovitine, 50 nM TSA or both for 22 h, first polar body extrusion and
      blastocyst formation in all treated groups were significantly improved compared
      with the etoposide-only group. The most significant improvement was observed when
      Roscovitine was present. Further immunofluorescent analysis of gammaH2A.X, an
      indicator of DNA damage, indicated that DNA damage was significantly decreased in
      all treated groups. This observation was further supported by analysing the
      relative mRNA abundance of DNA repair-related genes, including meiotic
      recombination 11 homolog A (MRE11A), breast cancer type 1 susceptibility protein
      (BRCA1), Recombinant DNA Repair Protein 51 (RAD51), DNA-dependent protein kinase
      catalytic subunit (PRKDC) and X-ray cross complementing gene 4 (XRCC4). Compared
      with the etoposide-only group, the experimental group with combined treatment of
      Roscovitine and TSA showed a significant decrease of all genes at germinal
      vesicle and MII stages. The Roscovitine-only treatment group revealed a similar
      tendency. Together, these results suggest that Roscovitine and TSA treatments
      could increase the capacity of oocytes to recover from DNA damage by enlisting
      DNA repair processes.

PMID- 30301511
TI  - Foreword.

PMID- 30301510
TI  - Follicular environment as a predictive tool for embryo development and kinetics
      in cattle.
AB  - Follicular fluid composition and the transcription pattern of granulosa cells
      were analysed to better comprehend associations between embryo development and
      morphokinetics. Bovine follicles were punctured and their respective follicular
      fluid and granulosa cells were collected. Cumulus-oocyte complexes derived from
      these follicles were matured and fertilised in vitro. Embryo morphology and
      kinetics were evaluated at 40 h after insemination, when embryos were classified
      as fast (FCL, four or more cells), slow (SCL, 2-3 cells) or non-cleaved (NCL).
      Their development was followed until the blastocyst stage. Glucose, pyruvate,
      cholesterol and oestradiol were quantified in the follicular fluid and the
      transcription pattern of 96 target genes was evaluated in granulosa cells by
      large-scale quantitative reverse transcription polymerase chain reaction.
      Follicular fluid from the blastocyst group had increased levels of glucose, total
      cholesterol and pyruvate compared to the non-blastocyst group, whereas higher
      levels of oestradiol were observed in the follicular fluid of embryos and
      blastocysts with fast cleavage. The transcriptional pattern revealed altered
      metabolic pathways between groups, such as lipid metabolism, cellular stress and
      cell signalling. In conclusion, both follicular fluid and granulosa cells are
      associated with the possibility of identifying follicles that may generate
      embryos with high potential to properly develop to the blastocyst stage.

PMID- 30301512
TI  - Hypervascular Pseudonodular Plaque-Like Ultrasound Morphology in Angiolymphoid
      Hyperplasia.
AB  - Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular
      proliferation characterized by solitary or multiple angiomatous lesions. It is
      most common in young or middle-aged women, and the lesions typically affect the
      head and neck, showing a particular predilection for the periauricular region.
      The differential diagnosis in patients with ALHE is broad and includes both
      benign and malignant conditions. We report on a series of cases of periauricular
      ALHE in which ultrasound imaging revealed an hypervascular, pseudonodular and
      plaque-like morphology with clinical and histologic correlations. It also
      evidenced vascular communication between lesions that appeared to be separate on
      clinical examination. Familiarity with such ultrasound presentations could help
      to improve diagnostic accuracy and facilitate disease monitoring in patients with
      ALHE.

PMID- 30301513
TI  - Kalman Inversion Stress Microscopy.
AB  - Although mechanical cues are crucial to tissue morphogenesis and development, the
      tissue mechanical stress field remains poorly characterized. Given traction force
      time-lapse movies, as obtained by traction force microscopy of in vitro cellular
      sheets, we show that the tissue stress field can be estimated by Kalman
      filtering. After validation using numerical data, we apply Kalman inversion
      stress microscopy to experimental data. We combine the inferred stress field with
      velocity and cell-shape measurements to quantify the rheology of epithelial cell
      monolayers in physiological conditions, found to be close to that of an elastic
      and active material.

PMID- 30301515
TI  - Milestones in the development of Spanish optometry.

PMID- 30301514
TI  - Effect of dsDNA on the Assembly Pathway and Mechanical Strength of SV40 VP1 Virus
      like Particles.
AB  - Simian virus 40 (SV40) is a possible vehicle for targeted drug delivery systems
      because of its low immunogenicity, high infectivity, and high transfection
      efficiency. To use SV40 for biotechnology applications, more information is
      needed on its assembly process to efficiently incorporate foreign materials and
      to tune the mechanical properties of the structure. We use atomic force
      microscopy to determine the effect of double-stranded DNA packaging, buffer
      conditions, and incubation time on the morphology and strength of virus-like
      particles (VLPs) composed of SV40 VP1 pentamers. DNA-induced assembly results in
      a homogeneous population of native-like, ~45 nm VLPs. In contrast, under high
      ionic-strength conditions, the VP1 pentamers do not seem to interact
      consistently, resulting in a heterogeneous population of empty VLPs. The
      stiffness of both in-vitro-assembled empty and DNA-filled VLPs is comparable.
      Yet, the DNA increases the VLPs' resistance to large deformation forces by acting
      as a scaffold, holding the VP1 pentamers together. Both disulfide bridges and
      Ca2+, important in-vitro-assembly factors, affect the mechanical stability of the
      VLPs: the reducing agent DTT makes the VLPs less resistant to mechanical stress
      and prone to damage, whereas Ca2+-chelating EDTA induces a marked softening of
      the VLP. These results show that negatively charged polymers such as DNA can be
      used to generate homogeneous particles, thereby optimizing VLPs as vessels for
      drug delivery. Moreover, the storage buffer should be chosen such that VP1
      interpentamer interactions are preserved.

PMID- 30301516
TI  - Characteristics of Neovascularization in Early Stages of Proliferative Diabetic
      Retinopathy by Optical Coherence Tomography Angiography.

PMID- 30301517
TI  - Editorial commentary: Confessions of a drug dealer.

PMID- 30301518
TI  - "Tweet"-format reflective writing: A hidden needs assessment?
AB  - BACKGROUND: Medical student reflection is integral for professional development.
      Preliminary findings suggest that short-format writing promotes reflection and
      identifies impactful experiences. We sought to determine whether reflective
      writing could be used as a clerkship needs assessment. METHODS: During their
      surgical clerkship, medical students submitted "tweet"-format reflections and
      completed a standardized evaluation. "Tweet" content was analyzed using modified
      grounded theory methods and coded by valence, content, and reflection. Sub-coding
      was conducted to compare feedback between "tweets" and evaluations. RESULTS: We
      analyzed 286 reflections and 214 evaluation comments; 176 "tweets" were
      reflective (62%). "Tweets" commented on "patient interaction" (53%), "educational
      experience" (38%), "physician interaction" (26%), and "career decisions" (10%). A
      significant difference was observed between "tweets" and evaluations with regard
      to the number that provided feedback on experiences with "critically ill or dying
      patients." CONCLUSIONS: Reflections provided real-time reactions to impactful
      clerkship events, notably those involving critically ill or dying patients. This
      focus on illness may represent an unmet need for discussions related to end of
      life care. Overall, reflections provided more actionable feedback compared to
      evaluations.

PMID- 30301519
TI  - Mechanistic insight into protein supported biosorption complemented by kinetic
      and thermodynamics perspectives.
AB  - In this review, we discussed the micro-level aspects of protein supported
      biosorption. The mechanism, surface chemistry in terms of energy interactions and
      electron transfer process (ETP) of peptide systems within protein are three
      important areas that provide mechanistic insight into protein supported
      biosorption. The functional groups in proteinous material like hydroxyl (-OH),
      carbonyl (>C=O), carboxyl (-COOH) and sulfhydryl (-SH) play a significant role in
      the biosorption of variety of pollutants such as metal ions, metalloids, and
      organic matters in wastewaters. The mechanistic aspects of biosorption are
      crucial not only for the separation process but also they contribute towards
      stoichiometric considerations and mathematical modelling process. The surface
      chemistry of applied biosorbents relies on interfacial components whose
      interaction energies are estimated with help of classical Derjaguin, Landau,
      Verwey, and Overbeek (DLVO) theory mathematically. Proteins are the fundamental
      molecules of many biomaterial used for the biosorption of contaminents and
      peptide bond is considered as the backbone of proteins. The charge variations on
      peptide bonding is the result of ETP whose discussion was made part of this
      review for understaning number of biological and technological processes of vital
      interests. In addition, this review was complemented by exhaustive overview of
      kinetic and thermodynamics perspectives of biosorption process.

PMID- 30301520
TI  - Isolated elevation of thyroglobulin in the follow-up of differentiated thyroid
      cancer, does it always indicate true persistent disease?

PMID- 30301521
TI  - Risk factors for systemic inflammatory response syndrome after percutaneous
      nephrolithotomy.
AB  - OBJECTIVES: To explore the risk factors for systemic inflammatory response
      syndrome (SIRS) after percutaneous nephrolithotomy (PCNL). METHODS: A
      retrospective chart review was performed to identify 1030 patients who had
      undergone PCNL from January 2014 to July 2016 in the Minimally Invasive Surgery
      Center. Multiple data, including age, sex, body mass index (BMI), operation time,
      Staghorn calculi, diabetes, Serun creatinine, preoperative urine culture and the
      urinary sediment microscopy white blood cell (WBC) were collected. These factors
      and postoperative SIRS were retrospectively analyzed. RESULTS: There were 108
      cases (10.49%) of SIRS among 1030 patients. The results of univariate analysis
      showed that sex (P=0.015), Staghorn calculi (P<0.001), preoperative urinary
      culture of Gram-negative bacteria (P<0.001) and preoperative urinary sediment
      microscopy WBC (+, ++, +++, ++++) (P<0.001, P<0.001, P=0.009, P=0.045) were
      correlated with postoperative SIRS (P<0.05). According to Multivariate analysis
      results, the likelihood of SIRS after PCNL increased with Staghorn calculi
      (P=0.01, OR=10.457, 95% CI=1.312-3.092), the urinary sediment microscopy WBC
      (+~++++) (P<0.001, OR=2.591, 95% CI=1.661-4.042) and positive urine culture for
      Gram-negative bacteria (P<0.001, OR=3.550, 95% CI=2.205-5.715). CONCLUSIONS:
      Staghorn calculi, the urinary sediment microscopy WBC and positive urine culture
      for Gram-negative bacteria are independent risk factors for SIRS. Patients
      affected by these risk factors should receive careful anti-infectious
      perioperative management for prevention of postoperative SIRS. LEVEL OF
      INCIDENCE: 4.

PMID- 30301522
TI  - Novel biomarkers in multiple myeloma.
AB  - Significant advancements have been made in the molecular mechanisms of
      myelomagenesis, diagnostic methods, prognostication, and the treatment options in
      multiple myeloma (MM) over the last decade. Despite these, MM remains a
      heterogeneous disease with differing outcomes. As myeloma treatment landscape
      continues to expand, personalized treatment that provides maximum benefit to a
      specific patient becomes more important. In the last few years, serum monoclonal
      proteins including the serum-free light chain assays, imaging, and cytogenetics
      have been used to predict the outcomes of MM patients receiving different types
      of therapies. With the development of novel technologies, more sensitive
      detection of residual disease using flow cytometry and next-generation sequencing
      has been possible. In addition, liquid biopsies using circulating tumor cells,
      tumor DNA, and novel immune biomarkers are potentially being investigated. These
      novel potential biomarkers not only accurately detect the mutational landscape of
      different cancers compared to standard methods but also serve as prognostic and
      predictive biomarkers for disease relapse and response to therapy. It is likely
      that we will be able to offer more targeted and risk-adapted therapeutic approach
      to patients with MM at different stages of their disease guided by these
      potential biomarkers.

PMID- 30301523
TI  - Motivational interviewing: A promising tool to address vaccine hesitancy.

PMID- 30301524
TI  - Promoting oral potassium administration in a tertiary care hospital: An eleven
      year study.
AB  - INTRODUCTION: Potassium is used to treat or prevent hypokalemia and exhibits all
      the characteristics of an intravenous to oral therapy conversion program. Despite
      this, the intravenous route for potassium replacement seems frequently
      unjustified. OBJECTIVES: To determine the impact of a conversion program on the
      use of intravenous and oral galenic forms in a university tertiary care hospital.
      METHODS: Two promotion campaigns were conducted in 2006 and 2009. The following
      years this was completed by pharmacist interventions during prescription analysis
      and face-to-face discussions with physicians during ward rounds. The consumption
      of products containing potassium was obtained by analyzing the hospital's
      financial database. RESULTS: The proportion of the oral route increased from 18%
      in 2006 to 22% in 2011, and from 25% in 2012 to 44% in 2016; the increase was
      significantly greater in the second period (P<0.0001). In 2016, in emergency,
      pulmonology, infectious diseases, and cardiology departments, the proportion of
      oral use ranged from 57% and 82%. The greatest progression from 2006 to 2016 was
      found for intensive care (4% vs. 12%) and visceral surgery departments (9% vs.
      34%) that increased approximately four-fold, followed by the emergency department
      (28% vs. 57%) that increased approximately two-fold. CONCLUSION: Promoting the
      oral route for potassium replacement modifies prescriber habits and is followed
      by a notable increase in the proportion of potassium administered orally
      irrespective of department type.

PMID- 30301525
TI  - Antibiotic anisomycin selectively targets leukemia cell lines and patient samples
      through suppressing Wnt/beta-catenin signaling.
AB  - Chronic myeloid leukemia (CML) responds well to BCR-ABL tyrosine kinase
      inhibitors (TKI), such as imatinib and dasatinib. However, these inhibitors have
      been less effective as single agents in the blast phase-CML. In this work, we
      show that anisomycin, a clinically available drug, targets CML cells at all
      stages of development and enhances BCR-ABL TKIs' efficacy. Anisomycin at
      nanomolar concentration inhibits proliferation and induces apoptosis in a panel
      of CML cell lines in a dose-dependent manner. It induces apoptosis CD34
      stem/progenitor cells isolated from patients with blast phase CML. Using colony
      formation and serial replating assays, we further show that anisomycin inhibits
      CML CD34 cell differentiation, proliferation and self-renewal. Additionally,
      anisomycin is less effective in normal bone marrow (NBM) CD34 cells, suggesting
      the selective anti-leukemia activity of anisomycin. Combination of anisomycin
      with imatinib or dasatinib achieves significantly better efficacy than TKI alone
      in leukemia cell lines and patient samples while sparing normal counterparts.
      Mechanistically, we demonstrate that p38 MAPK/JNK activation is not required for
      anti-leukemia activities of anisomycin. Instead, anisomycin displays preferential
      inhibitory effects to Wnt/beta-catenin-mediated signaling in CML. Our work
      provides the preclinical evidence on the potent efficacy of anisomycin in
      leukemia and its mechanisms of action. Our work suggests that anisomycin is a
      potential drug to overcome resistance to BCR-ABL TKI treatment in blast phase
      CML.

PMID- 30301526
TI  - Transgelin-1 (SM22alpha) interacts with actin stress fibers and podosomes in
      smooth muscle cells without using its actin binding site.
AB  - Transgelin-1 (SM22alpha) has been recognized as a smooth muscle marker and a
      tumor suppressor, but many details of the working mechanisms remain unclear.
      Transgelin-1 belongs to the calponin family of actin-binding proteins with an N
      terminal calponin homology domain (CH-domain) and a C-terminal calponin-like
      module (CLIK23). Here, we demonstrate that transgelin-1 interacts with actin
      stress fibers and podosomes in smooth muscle cells via its type-3 CH-domain,
      while CLIK23 is dispensable for the binding to the actin structures. We further
      suggest that the EF-hand motif in transgelin-1 contributes to proper folding of
      the CH-domain and in turn to the interaction with the actin structures. These
      results are in contrast to the ones reported in in vitro studies that
      demonstrated CLIK23 was necessary for the transgelin-1-actin binding, while the
      CH-domain was not. Besides, within cells, transgelin-1 phosphorylation at Ser181
      in CLIK23 did not affect its colocalization with the actin structures, while the
      same phosphorylation was reported in in vitro studies to negatively regulate
      actin binding. Thus, our results suggest the molecular basis of intracellular
      interaction between transgelin-1 and actin, distinct from that in vitro. The
      actin binding capability intrinsic to CLIK23 may not appear within cells probably
      because of the weaker competition for actin binding compared to other actin
      binding molecules.

PMID- 30301527
TI  - Interleukin-18 binding protein attenuates lipopolysaccharide-induced acute lung
      injury in mice via suppression NF-kappaB and activation Nrf2 pathway.
AB  - Interleukin (IL)-18 belongs to a rather large IL-1 gene family and is a
      proinflammatory cytokine. IL-18 plays important roles in lung injury. IL-18
      binding protein (IL-18BP), a natural antagonist of IL-18, binds IL-18 with high
      affinity. IL-18BP is able to neutralize IL-18 biological activity and has a
      protective effect against renal fibrosis. The aim of this study was to evaluate
      the potential protective effect of IL-18BP on lipopolysaccharide (LPS)-induced
      acute lung injury (ALI) in mice and to illuminate the underlying mechanisms.
      Results indicated that pretreatment with IL-18BP significantly attenuated LPS
      induced pulmonary pathological injury. Meanwhile, IL-18BP pretreatment markedly
      inhibited infiltration of inflammatory cell and release of inflammatory factor in
      ALI mice in vivo and in primary macrophages after LPS insult in vitro. IL-18BP
      treatment dramatically reduced oxidative stress through increasing superoxide
      dismutase (SOD) and glutathione (GSH) contents, and decreasing the levels of
      malondialdehyde (MDA) and reactive oxygen species (ROS) in LPS-induced ALI mice
      and primary macrophages. Additionally, IL-18BP was also observed to markedly
      decreased the activation of nuclear factor-kappa B (NF-kappaB) and upregulated
      the nuclear factor erythroid 2-related factor 2 (Nrf2). Taken together, IL-18BP
      possessed protective effect against LPS-induced ALI, which might be associated
      with its regulation of NF-kappaB and Nrf2 activities. The results rendered IL
      18BP worthy of further development into a pharmaceutical drug for the treatment
      of ALI.

PMID- 30301528
TI  - Helicobacter pylori flagellin: TLR5 evasion and fusion-based conversion into a
      TLR5 agonist.
AB  - Helicobacter pylori is a flagellated bacterium of the Epsilonproteobacteria class
      that causes peptic ulcers. Flagellin is a primary structural protein that
      assembles into the flagellar filament. Flagellins from bacteria that belong to
      the Gammaproteobacteria and Firmicutes groups are detected by Toll-like receptor
      5 (TLR5) in the host, triggering the innate immune response, and thus have been
      studied for the development of vaccines against diverse infections through fusion
      with protein antigens. However, H. pylori flagellin (hFlg) does not stimulate
      TLR5, allowing H. pylori to evade TLR5-mediated immune surveillance. The
      unresponsiveness of TLR5 to hFlg, along with the tendency of the hFlg protein to
      precipitate, limits the utility of hFlg for H. pylori vaccine development. Here,
      we report a soluble hFlg derivative protein that activates TLR5. We performed
      expression and purification screens with full-length and fragment hFlg proteins
      and identified the hypervariable domains as the soluble part of hFlg. The
      hypervariable domains of hFlg were engineered into a TLR5 agonist through fusion
      with the TLR5-activating Bacillus subtilis flagellin. Furthermore, based on
      comparative sequence and mutation analyses, we reveal that hFlg evolved to evade
      TLR5 detection by modifying residues that correspond to a TLR5-activation hot
      spot.

PMID- 30301529
TI  - Short fish-origin DNA elements served as flanking sequences in a knockdown
      cloning vector enabling the generation of a functional siRNA molecule in
      mammalian cells and fish embryos.
AB  - Improving the quality of a siRNA-knockdown cloning vector requires simpler,
      shorter, and more effective flanking sequences. In this study, we designed such
      flanking sequences based on those found in zebrafish pre-miR3906, namely,
      internal element (IE) 1 and IE2. We engineered a vegf-shRNA fragment flanked by
      an 80-bp IE1/IE2 and then inserted into the 3' UTR of GFP reporter cDNA driven by
      a cytomegalovirus promoter to obtain a plasmid containing gfp-IE-vegf-shRNA-polA.
      Upon microinjection of this plasmid into zebrafish embryos, we found that IE
      flanking sequences could effectively induce the production of vegf-shRNA
      fragment, which was then processed into a functional siRNA to silence the target
      vegf121 gene. Northern blot showed that the vegf-shRNA fragment was cleaved from
      gfp-IE-vegf-shRNA-polA, resulting in the loss of polyA tails, subsequently
      degrading the remaining RNA-containing GFP. Moreover, Western blot revealed that
      addition of IE-based vegf-shRNA fragment could markedly decrease the expression
      of VEGF. Finally, to facilitate a more versatile application of the IE-based
      knockdown vector, we generated an inducible expression vector in which IE-vegf
      shRNA was constructed downstream in a Tet-on system to generate a Tet-on-IE-vegf
      shRNA construct. After doxycycline induction, the protein level of VEGF in SW620
      cells harboring the Tet-on-IE-vegf-shRNA construct was decreased 77%.
      Interestingly, when SW620 cells harboring Tet-on-IE-vegf-shRNA cells were induced
      and transplanted into zebrafish embryos, we found that abnormal branch of the sub
      intestinal vessels was reduced in the recipient embryos, suggesting that vegf
      shRNA cleaved from Tet-on-IE-vegf-shRNA-polA was processed into a functional vegf
      siRNA in embryos suppressing endogenous VEGF and reducing tumor angiogenesis.
      Therefore, we conclude that fish-origin IEs are flanking sequences with short,
      simple, and effective DNA elements. This IE-based knockdown cloning vector
      provides a new alternative material to facilitate the generation of functional
      siRNA with which to perform loss-of-function experiments, both in vitro
      (mammalian cells) and in vivo (zebrafish embryos).

PMID- 30301530
TI  - Far upstream element-binding protein 1 is up-regulated in pancreatic cancer and
      modulates immune response by increasing programmed death ligand 1.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer
      related death worldwide. So far, almost all treatments are almost ineffective for
      pancreatic cancer. Thus, there is an urgent need to develop novel therapeutics
      for pancreatic cancer treatment. Immune checkpoints blockade therapies, including
      anti-PD-L1 and anti-PD-1, show promising anti-tumor efficacy for a various type
      of solid tumors. However, pancreatic cancer is disappointed for anti-PD-L1
      therapy alone. The expression level of PD-L1 is considered as one of determinant
      of checkpoint immunotherapy efficacy. The far upstream element-binding protein 1
      (FUBP1) is an important transactivator of c-Myc proto-oncogene. Here, we
      demonstrate that FUBP1 is overexpressed in pancreatic cancer and associated with
      poor prognosis. Moreover, we show that FUBP1 promotes tumor cell proliferation
      and migration and regulates the cancer cell immunity by increasing the PD-L1
      expression mediated by Myc in pancreatic cancer cells. Taken together, these
      findings uncover important aspects of the function of FUBP1 in cancer immunity
      and elucidated the specific mechanism regulating PD-L1 expression. Targeting
      FUBP1 may be a novel therapeutic strategy to overcome the immunotherapy
      resistance in pancreatic cancer.

PMID- 30301531
TI  - Real-time monitoring of IL-6 and IL-10 reporter expression for anti-inflammation
      activity in live RAW 264.7 cells.
AB  - In previous study, we suggested that the interleukin (IL)-6 and IL-10 could serve
      as a good biomarker for anti-inflammation that related to chronic inflammatory
      disease. Recently, we are finding new anti-inflammation compounds from natural
      products by screening of IL-6 and IL-10 levels. Although, we could measure IL-6
      and IL-10 levels by several methods. However, all methods could not measure
      continuous kinetic of IL-6 and IL-10 levels. Most methods have multiple steps and
      take a long time. Therefore, there is no a suitable method for screening. To this
      end, we established IL-6 and IL-10 promoter assay which can monitor with
      reference gene as Glyceraldehyde 3-phosphate dehydrogenase (gapdh) promoter in
      living single cell. It could determine IL-6 and IL-10 levels continuously in real
      time within two steps. We evaluated IL-6 and IL-10 reporter expression in LPS
      induced RAW 264.7 cells with well-known anti-inflammatory compounds such as
      quercetin, xanthones, beta-D-glucan and dexamethasone. As the results, the
      expression of IL-6 and IL-10 reporters were strongly induced by LPS. The
      expression of IL-6 reporter was inhibited by all anti-inflammation compounds in
      LPS-induced RAW 264.7 cells. The expression of IL-10 reporter was inhibited by
      quercetin, xanthones and dexamethasone in LPS-induced RAW 264.7 cells. While,
      expression of IL-10 reporter was induced by beta-D-glucan. These results
      indicated that this assay could use for determination of IL-6 and IL-10 reporter
      expression in LPS-induced RAW 264.7 cells for anti-inflammation activity.
      Moreover, the results showed that natural compounds have an effect on the time
      course of IL-6 and IL-10 expressions. Therefore, real-time monitoring has a merit
      for natural compounds screening. We suggested that this assay could serve as a
      compound screening assay for anti-inflammation activity.

PMID- 30301533
TI  - CTLA-4 regulates T follicular regulatory cell differentiation and participates in
      intestinal damage caused by spontaneous autoimmunity.
AB  - Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is a co-inhibitory molecule
      expressed by T cells and is required for immune regulation and inflammation
      prevention. In clinical patients, the CTLA-4 mutation causes spontaneous immune
      related early-onset Crohn's disease; however, its potential mechanism is still
      unknown. In the current study, we found that defects in CTLA-4 in CD4 cells lead
      to limited differentiation of T follicular regulatory (Tfr) cells and relatively
      increased T follicular helper (Tfh) cells and spontaneous B cell germinal centres
      (GCs) responses that trigger the accumulation of autoantibodies in intestinal
      epithelial cells. In addition, the deficiency of Tfr cells caused by defects in
      CTLA-4 causes these cells to lose their function of inhibiting the non-specific
      immune response produced during the specific humoural immune response induced by
      MCMV (mouse cytomegalovirus), resulting in acute intestinal injury and death in
      mice. The lack of Tfr cells may be responsible for the immunosuppressive disorder
      of inflammatory bowel disease caused by CTLA-4 deficiency. In conclusion, we
      verified that CTLA-4 may be required for Tfr cell differentiation and production.
      Tfr cells inhibit B cell responses and prevent humoural autoimmune-mediated
      intestinal damage by regulating Tfh-dependent GC responses.

PMID- 30301532
TI  - Deletion of ApoM gene induces apoptosis in mouse kidney via mitochondrial and
      endoplasmic reticulum stress pathways.
AB  - Apolipoprotein M (ApoM) is involved in lipid metabolism, and especially is
      involved in reverse cholesterol transport. However, the relationship between ApoM
      and apoptosis has been rarely reported. This study aimed to investigate the
      effect of ApoM on apoptosis using an ApoM gene-deficient mice (ApoM-/-) model and
      a mouse mesangial cell model with suppressed ApoM gene expression. First, we
      observed by transmission electron microscopy that mitochondrial damage and
      endoplasmic reticulum stress were abnormally altered in the kidneys of ApoM-/-
      mice compared with wild-type mice, showing mitochondrial swelling, vacuolization,
      myeloid changes, and expansion of the rough endoplasmic reticulum. At the
      molecular level, the expression of pro-apoptotic related proteins such as AIF,
      Bax, chop, clever-caspase 3, clever-caspase 7, clever-caspase 9, and clever
      caspase 12 increased, and the expression of anti-apoptotic protein Bcl-2
      decreased. Secondly, by interfering with the expression of the ApoM gene in mouse
      mesangial cells, we found that, compared with the control group (NC-si), the
      cells of the experimental group (siApoM) showed decreased cell viability, nuclear
      chromatin condensation, nuclear lysis, and an increased proportion of early
      apoptotic cells. The results in cells at the molecular level were consistent with
      those at the tissue level. These data indicated that the deletion of the ApoM
      gene led to upregulation of apoptosis in mouse kidney tissues and mesangial cells
      through the mitochondrial and endoplasmic reticulum pathways.

PMID- 30301535
TI  - Bringing patient-centered innovation to Patient Education & Counseling.

PMID- 30301537
TI  - Increasing carbon source uptake rates to improve chemical productivity in
      metabolic engineering.

PMID- 30301538
TI  - Mobility is a fundamental human right: Factors predicting attitudes toward self
      directed mobility.
AB  - BACKGROUND: Emergent disability studies research is interested in the community's
      views on how disability, including self-directed mobility, influences social and
      environmental policies. We anticipate that individuals' alignment with disability
      models, or sets of assumptions about the cause, nature, and treatment of
      disability, will influence attitudes about self-directed mobility. Self-directed
      mobility is defined as mobility that is controlled by an individual and may
      include walking or assisted ambulation through the use of mobility technology
      such as prosthetics, walking aids, manual wheelchairs, or motorized wheelchairs.
      OBJECTIVE: The purpose of this study was to explore how demographic factors,
      contact with people with disabilities, attitudes toward people with disabilities,
      and alignment with social or medical models of disability predict attitudes
      toward self-directed mobility. METHODS: 1545 students at a public university
      completed demographic questions, and measures of disability attitudes, disability
      model orientation, and self-directed mobility. RESULTS: The predictors explained
      16.60% of the variance in participants' attitudes toward self-directed mobility
      (R2 = 0.166, F(7,1537) = 43.9, p < .001). Significant predictors included: female
      gender (beta = -0.14, p < .01), more positive attitudes toward people with
      disabilities (beta = -0.30, p < .001), and social model orientation (beta = 0.59,
      p < .001). CONCLUSIONS: Participants who more strongly agreed with disability as
      a social construct (social model) were in stronger agreement that self-directed
      mobility is a fundamental right. Future research extending to rehabilitation
      professionals is warranted.

PMID- 30301539
TI  - Retraction notice to " Effect of electropulsing treatment and ultrasonic striking
      treatment on the mechanical properties and microstructure of biomedical ti-6Al-4V
      alloy"JCBM 40 (2014) 287-296.

PMID- 30301540
TI  - Retraction notice to "Mechanical properties and phase transition of biomedical
      titanium alloy strips with initial quasi-single phase state under high-energy
      electropulses" JCBM 42 (2015) 100-115.

PMID- 30301541
TI  - Outcomes of Acute Myocardial Infarction in Heart Transplant Recipients.
AB  - Heart transplantation (HT) recipients represent a growing patient population.
      Although mechanisms might differ, coronary artery disease is an important cause
      of morbidity in this group. Limited data are available on the outcomes of acute
      myocardial infarction (AMI) in HT in comparison to general population (non-HT).
      The study population was extracted from the National Readmissions Data 2014 using
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes for AMI and HT. The study outcomes included in-hospital all-cause
      mortality, length of hospital stay (LOS), cardiogenic shock, acute kidney injury,
      the likelihood of receiving invasive left-sided cardiac catheterization with
      and/or without percutaneous coronary intervention (PCI) and 30-day readmission
      rates. A total of 259,794 discharges with a principal diagnosis of AMI were
      identified, in which 789 had a history of HT. In comparison to non-HT, HT group
      was associated with longer LOS (5.9 vs 4.9 days, p <0.01), more cardiogenic shock
      (8.8% vs 6.4%, p <0.01), more acute kidney injury (26.2% vs 17.6%, p <0.01), less
      catheterization (59.7% vs 75.1%, p <0.01), less use of PCI (35.2% vs 50.0%, p
      <0.01), and higher 30-day readmission rate (21.3% vs 14.4%, p <0.01). However,
      there was no statistically significant difference in all-cause mortality (6.8% vs
      5.4%, p = 0.07). In conclusion, compared with non-HT, HT with AMI was associated
      with longer LOS, more in-hospital morbidity, lower likelihood of receiving
      invasive treatment (including PCI), and higher 30-day readmission rates. There
      was no significant difference in all-cause mortality.

PMID- 30301542
TI  - Raising the Bar by Lowering the Target: Integrating PCSK9 Inhibitors Into
      Hypercholesterolemia Management.
AB  - This CME-accredited CME Snapshot seven-part series is intended for interventional
      cardiologists, other cardiologists, lipidologists, endocrinologists, and other
      diabetologist physicians involved in the ongoing management of patients with
      persistent hypercholesterolemia. During these activities, expert faculty will
      participate in a series of interactive discussions on the latest evidence and
      their clinical experience managing patients with persistently elevated low
      density lipoprotein cholesterol levels using nonstatin lipid-lowering
      medications, including inhibitors of the enzyme protein convertase subtilisin or
      kexin type 9 (PCSK9). (Online access:
      https://lipidsnapshotcme.elsevierresource.com/.).

PMID- 30301543
TI  - Patterns of Acute Myocardial Infarction in Taiwan from 2009 to 2015.
AB  - Most studies about the trends of acute myocardial infarction (AMI) were based on
      the data from Western countries. In recent years, little information is available
      from Asia since 2010. This study assessed the nationwide trends of AMI in Taiwan
      from 2009 to 2015. Using data from the Taiwan National Health Insurance Research
      Database, we identified 100,570 adult patients hospitalized for AMI from 2009 to
      2015 and examined the temporal trends in the incidence of AMI. Overall, the age-
      and gender-adjusted incidence of AMI (per 100,000 persons) remained constant from
      49.8 in 2009 to 50.7 in 2015. The incidence of AMI increased 30.3% and 29.4% in
      the young male and female populations (<55 years), whereas in other age groups,
      the incidence decreased or remained unchanged. The ratio of non-ST-segment
      elevation MI (NSTEMI) to STEMI incidence increased from 1.93 in 2009 to 2.47 in
      2015. In young men (<55 years), a 49.8% increase in NSTEMI was observed. The
      prevalence of dyslipidemia increased significantly and it was the most common
      risk factor of AMI in young patients. Despite being increasingly used,
      percutaneous coronary intervention and secondary preventive medications,
      including dual antiplatelet therapy, angiotensin converting enzyme
      inhibitor/angiotensin receptor blocker, beta blocker and statin, were less
      prescribed for NSTEMI compared with STEMI. The in-hospital mortality of STEMI
      continued to decrease from 2013 to 2015 (8.8% to 7.6%), but not in NSTEMI (13.3%
      to 13.5%). In conclusion, our study revealed a marked increase of NSTEMI in young
      Taiwanese male population in recent years. Despite the increased utilization of
      percutaneous coronary intervention and guideline-recommended medications, the
      overall in-hospital mortality of NSTEMI remained stagnating in Taiwan.

PMID- 30301544
TI  - [Unusual cause of Takotsubo cardiomyopathy after pacemaker implantation].
AB  - Since its first description in Japan in 1990, Takotsubo (stress) cardiomyopathy
      has gained worldwide recognition. The disease is characterized by transient
      systolic and diastolic left ventricular dysfunction with a variety of wall-motion
      abnormalities. She predominantly affects elderly women and she is often preceded
      by an emotional or physical trigger. In the acute phase, the clinical
      presentation, electrocardiographic findings and biomarker profiles are often
      similar to those of an acute coronary syndrome. Although, the cause of Takotsubo
      cardiomyopathy remains unknown, the role of the brain-heart axis in the
      pathogenesis of the disease has been described. The potential role of
      catecholamine excess in the pathogenesis of Takotsubo cardiomyopathy has been
      long debated, and as such beta-blockers have been proposed as a therapeutic
      strategy. Currently, the treatment is not codified and it adapts according to
      clinical symptomatology. It seems difficult to summarize all the factors to
      provoque the cardiomyopathy, we describe a case of Takotsubo after a pacemaker
      (PM) implantation and to give a recent progress on this heart disease.

PMID- 30301545
TI  - [Place of the exercise stress test at the sportsman].
AB  - Is the stress test still part of the useful examinations in the detection of risk
      heart disease in sports subjects? Should we continue to use it as a surveillance
      examination in coronary sports patients? Meta-analysis, considering a ST subshift
      of more than 1mm as a criterion for positivity, underline the low prevalence of
      abnormal examinations and a significant rate of false-positives. But for the
      diagnosis of coronary artery disease, it is mainly the evolution of the ST
      segment to effort or recovery and the occurrence of stress arrhythmias that
      detect true positivity. When coronary risk is more important (presence of risk
      factors, resumption of sport, intense and prolonged efforts), it seems lawful to
      recommend such a review on a regular basis among men over 40 years of age with
      two risk factors but Also among veterans taking up sport after a period of
      prolonged inactivity. For the asymptomatic coronary athlete the stress test
      remains at the centre of the final decision for the resumption of a sport in
      competition irrespective of the method of revascularization. Of course the stress
      test, even inevitable, remains flawed in the detection of coronary artery disease
      in the asymptomatic athlete. However, it provides additional information on the
      condition of being maximal, and attaching importance to arrhythmias, the
      tensional profile and the maximum power developed in addition to the ST segment's
      only study.

PMID- 30301546
TI  - [Infectious endocarditis: Experience of a cardiology department at Oran
      university hospital].
AB  - INTRODUCTION: Infectious endocarditis (IE) is a serious disease that has
      continued to evolve in diagnostic and therapeutic terms. AIM: To analyze the
      diagnostic and out come profile. METHODS: We collected 57 (IE) cases with a
      definite diagnosis according to the modified Duke criteria. Patients were
      admitted consecutively to the Cardiology Department of the Oran university
      hospital from January 2011 to June 2017. Among the variables studied: clinical
      data, paraclinic data, therapeutic management and hospital outcome. RESULTS: The
      mean age was 40.5+/-15 years (extreme 16-67 years), with a male predominance (sex
      ratio=1.5). This was a native valve IE in 70% of cases, on valve prosthesis in
      15.5% of patients, on congenital heart disease in 2% and on pacemaker probe in 4%
      of cases. The entrance door was dominated by oral origin. Blood cultures were
      positive only in 51% of cases. The most commonly implicated organism in
      staphylococci in 22.6%, streptococcus in 18.9% and brucellosis in 3.8%.
      Ultrasound data revealed vegetation (83%), cardiac abscess (19%), valvular
      perforation (15.1%) and prosthesis disintegration (7.5%). Complications were
      mainly neurological complications (27%) and hemodynamics (26%). Cardiac surgery
      occurred in 29% of patients. Hospital mortality was 26%, predictive factors were
      staphylococcal AI (P<0.001), cardiac insufficiency (P<0.001) and neurological
      complications (P=0.04). CONCLUSION: Infectious endocarditis is a serious disease
      in the absence of surgery. The diagnosis is based on echocardiography in the
      first place and blood cultures. The population is often young revealing the EI by
      complications; its prevention is the best way to improve its prognosis.

PMID- 30301548
TI  - [Unusual cause of acute coronary syndrome: Horton's disease].
AB  - The pathophysiology of acute coronary syndromes is in most cases due to the
      erosion or rupture of a plaque with consequent thrombotic obstruction of coronary
      artery. In a few cases, the mechanism is different, this not modifying the
      initial management but imposing special techniques for diagnosis and therapeutic
      management. We report a clinical case of a patient supported for an acute
      coronary syndrome, in a context of impaired general condition and biological
      inflammatory syndrome revealing a Horton's disease.

PMID- 30301547
TI  - [VIVOPTIM: Feedback of an e-Health experimental program of primary prevention of
      cardiovascular risk on 30 to 70 years old volunteers].
AB  - Today by the e-health and the telemedicine, many people are more and more
      interested by the improvement of disease knowledge on cardiovascular diseases and
      associated risk factors, personalized self management support follow-up and e
      Health monitoring. MGEN is a not-for-profit complementary health insurance gave
      itself the ways to use the new digital tools in health. MGEN developed an
      original and personalized program VIVOPTIM for the primary prevention of the
      cardiovascular risks for their members. The VIVOPTIM Pilot program is based upon
      digital services and was experimented by November 2015 to December, 2017 with
      8000 members of the MGEN, from 30 to 70 years old and resident in two French
      areas (Occitanie and Bourgogne Franche-Comte). The assessment of the experiment
      VIVOPTIM e -health program was positive for the personalized cardiovascular
      support and for their health. Therefore, the MGEN generalized the VIVOPTIM
      program of cardiovascular prevention, to the whole France on July 11th, 2018.

PMID- 30301549
TI  - Thrombocytopenia independently predicts death in idiopathic PAH.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive vascular
      disorder with a high mortality. Clinical experience and small case series suggest
      thrombocytopenia may be frequent in this population and associated with a poor
      prognosis. We sought to estimate the prevalence of thrombocytopenia in patients
      with PAH and characterize its association with disease characteristics and
      patient outcome. METHODS: Single center cohort study of 714 incident adult
      patients with Group 1 PH who were evaluated for baseline platelet count at the
      time of diagnosis. Pts were stratified into three groups: normal platelet count
      (>150 * 109/L), Grade 1 thrombocytopenia (75-149 * 109/L) and Grade 2-4
      thrombocytopenia (<75 * 109/L). RESULTS: The median platelet count was 209 *
      109/L (IQR 163, 264). There were 572 (80%) pts without thrombocytopenia, 107
      (15%) with Grade 1 and 35 (5%) with Grade 2-4 thrombocytopenia. The median pt age
      was 55years (IQR 44-65) with no difference between platelet groups (p = 0.85).
      Men were more likely to have thrombocytopenia (62, 34%) than women (80, 15%, p <
      0.0001). Thrombocytopenia was frequent with portopulmonary PAH (84%) as opposed
      to idiopathic PAH (iPAH; 14%) or connective tissue disease associated PAH (12%).
      Platelet counts were not associated with functional class symptoms, the degree of
      right ventricular enlargement or dysfunction or tricuspid regurgitation by
      echocardiography. Invasive hemodynamics of right atrial pressure, mean pulmonary
      artery pressure and pulmonary vascular resistance were also similar between
      platelet groups. Thrombocytopenia was associated with higher mortality in iPAH
      patients (age- and sex-adjusted 5 year mortality [HR 1.95 (1.20, 3.08) p = 0.008]
      but not in other etiology groups. In a multivariate model of iPAH patients
      (adjusted for age, sex, DLCO, PVR, creatinine and 6MW distance) thrombocytopenia
      was most predictive of 5-year mortality [HR 1.68 (1.32, 2.12), p < 0.0001].
      CONCLUSION: Thrombocytopenia in the context of iPAH portends a poor prognosis and
      is a simple independent factor to consider in judging severity of disease.

PMID- 30301550
TI  - Does the activity of ankle plantar flexors differ between limbs while healthy,
      young subjects stand at ease?
AB  - Inferences on the active contribution of plantar flexors to the stabilisation of
      human standing posture have been drawn from surface electromyograms (EMGs).
      Surface EMGs were however often detected unilaterally, presuming the myoelectric
      activity from muscles in a single leg reflects the pattern of muscle activation
      in both legs. In this study we question whether surface EMGs detected from
      plantar flexor muscles in both legs provide equal estimates of the duration of
      activity. Arrays of surface electrodes were used to collect EMGs from
      gastrocnemius and soleus muscles while twelve, young male participants stood at
      ease for 60 s. Muscles in each leg were deemed active whenever the Root Mean
      Square amplitude of EMGs (40 ms epochs) detected by any channel in the arrays
      exceeded the noise level, defined from EMGs detected during rest. The Chi-Square
      statistics revealed significant differences in the relative number of active
      periods for both muscles in 10 out of 12 participants tested, ranging from 2% to
      65% (chi2 > 17.90; P < 0.01). Pearson correlation analysis indicated side
      differences in the duration of gastrocnemius though not soleus activity were
      associated with the centre of pressure mean, lateral position (R = 0.60; P =
      0.035). These results suggest therefore that surface EMGs may provide different
      estimates of the timing of plantar flexors' activity if collected unilaterally
      during standing and that asymmetric activation may be not necessarily associated
      with weight distribution between limbs. Depending on the body side from which
      EMGs are collected, the active contribution of plantar flexors to standing
      stabilization may be either under- or over-valued.

PMID- 30301551
TI  - Structures and dynamics of carbon-black in suspension probed by static and
      dynamic ultrasound scattering techniques.
AB  - Carbon black (CB) suspension exhibits various structures depending on the
      properties of solvent and dispersant as well as the preparation process of
      suspension. In most cases, CB particles do not exist as independent nanoparticles
      but as aggregates or agglomerates. In order to evaluate the size distribution at
      different level of hierarchal structure, we carried out static/dynamic ultrasound
      scattering analysis for the CB suspensions in alcohol and/or water with or
      without Nafion, a perfluorinated polymer. The potential of the dynamic ultrasound
      scattering technique was demonstrated by discriminating diffusing nanoparticles
      and micron-sized aggregates/agglomerates without dilution of the sample.
      Particularly, suppression of large agglomerates by addition of Nafion was clearly
      observed. Phosphotungstic acid (PWA), a family of polyoxometalate, was also
      employed to obtain smaller unit structures of the CB particles without formation
      of aggregation after decomposition of CB. The possible structures of the CB/PWA
      suspensions with and without Nafion were also discussed.

PMID- 30301552
TI  - Nonlinear scattering and mode conversion of Lamb waves at breathing cracks: An
      efficient numerical approach.
AB  - This article presents an efficient numerical approach to the investigation of
      nonlinear scattering and mode conversion phenomena of Lamb waves as they interact
      with breathing cracks. A Local Interaction Simulation Approach (LISA) is adopted,
      which possesses the versatility to capture arbitrary damage profiles. The stick
      slip contact dynamics is implemented in the LISA model via the penalty method,
      which captures the nonlinear interactions between Lamb waves and breathing
      cracks. The LISA framework achieves remarkable computational efficiency with its
      parallel implementation using Compute Unified Device Architecture (CUDA) executed
      on powerful GPUs. A small-size LISA model with absorbing boundaries is tailored
      for the purpose of extracting the Lamb wave scattering and mode conversion
      features. Due to the explicit parallel CUDA implementation and the small-size
      model setup, the computation is highly efficient. Numerical case studies on
      nonlinear scattering of Lamb waves from breathing cracks are given. Distinctive
      higher harmonic generation and selective mode conversion phenomena are presented
      using the complex-valued Wave Damage Interaction Coefficients (WDICs) containing
      both amplitude and phase information of the scattered wave field. The effect of
      oblique incident angle on nonlinear scattering phenomenon is investigated. The
      rough crack surface feature with initial openings and closures is also considered
      to better approximate fatigue cracks in practical engineering scenarios. In
      addition, the wave amplitude effect on the nonlinear scattering and mode
      conversion is studied. This research may provide guidelines for the effective
      design of sensor arrays utilizing nonlinear Lamb waves for fatigue crack
      detection.

PMID- 30301553
TI  - Inflammation in reproduction, pregnancy and development.

PMID- 30301554
TI  - Bevacizumab: Is the lower the better for glioblastoma patients in progression?
AB  - INTRODUCTION: Based on the radiological responses obtained with a schedule of ten
      mg/kg every two weeks bevacizumab was approved by the FDA for recurrent
      glioblastomas. Due to the negative results concerning overall survival of
      patients receiving bevacizumab, the European application was rejected. Despite
      this, many centers apply an off-label prescription. Our aim was to evaluate the
      safety and efficacy of schedules of low doses of bevacizumab. METHODS: From
      September 2013 to August 2016, we recruited patients with progressive
      glioblastoma, whatever the previous treatments. We compared a routine control
      group (CG) of ten mg/kg, to a low dose group (LDG) composed of 5 subgroups: G5:
      five mg/kg, G4: four mg/kg, G3: three mg/kg, G2: two mg/kg, G1: one mg/kg; each
      patient was treated with the same dose every two weeks. RESULTS: Fifty-three
      patients were treated: 20 women and 33 men, 24 in the CG and 29 in the LDG. The
      median age at diagnosis was 62 years [35.0-77.0]. No statistical difference was
      found in overall survival either for the CG or the LDG (P=0.086) or among groups
      (P=0.251), with even a trend toward improvement for LDG: 62 weeks [20-145] versus
      73 weeks [18-178]. The median progression free survival was comparable: 19.5
      weeks [6.0-54.0] for the CG and 15.0 weeks [0.0-134.0] for the LDG (P=0.221).
      Bevacizumab was stopped either due to progression (45.1%) or toxicity (52.9%),
      without significant differences between doses but maybe less toxicities in the
      LDG (16.7% for toxicity in G1). DISCUSSION: Use of bevacizumab at progression at
      lower than usual doses seems to give the same results as the standard dose
      without giving additional toxicity.

PMID- 30301555
TI  - Intralesional Macular Atrophy in Anti-Vascular Endothelial Growth Factor Therapy
      for Age-Related Macular Degeneration in the IVAN Trial.
AB  - PURPOSE: To report on the development and progression of macular atrophy (MA) and
      its relationship with morphologic and functional measures in study and fellow
      eyes in the Inhibition of vascular endothelial growth factor (VEGF) in Age
      related Choroidal Neovascularisation trial. DESIGN: Reading center analysis of
      data from a randomized controlled trial. PARTICIPANTS: Participants with
      previously untreated neovascular age-related macular degeneration (nAMD) in the
      study eye. METHODS: Color, fluorescein angiography (FA) and OCT images acquired
      at baseline and during the 2-year follow-up were graded systematically for
      presence of MA. Regression models were constructed to explore relationships
      between MA and lesion morphology and vision measures (best-corrected distance and
      near acuity, reading speed and index, contrast sensitivity). MAIN OUTCOME
      MEASURES: Primary outcome was development of intralesional MA (>=175 MUm greatest
      linear dimension of choroidal vessels seen on FA and/or color, aided by OCT)
      lying within the maximum footprint of the neovascular lesion. RESULTS: Study eye
      data were available for 594 of 610 participants; 57 (9.6%) showed intralesional
      MA at baseline. Incident intralesional MA occurred in 24.4% by the final visit
      and extralesional MA in only 1.54%. In fellow eyes, an established nAMD lesion
      was present at baseline in 248 of whom 42 (16.9%) showed intralesional MA at
      baseline and 32 (12.9%) developed incident intralesional MA. The odds of incident
      intralesional MA by final visit were lower in study eyes that had >=50% classic
      CNV at baseline (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.19-0.80;
      P = 0.010), subretinal fluid at final visit (OR, 0.41; 95% CI, 0.25-0.76; P =
      0.004), or pigment epithelial detachment at final visit (OR, 0.40; 95% CI, 0.21
      0.74; P = 0.004). Secondary analyses of incident or progressed intralesional MA
      in study eyes supported these findings, with odds increasing if the fellow eye
      had baseline intralesional MA (OR, 2.43; 95% CI, 1.09-5.44; P = 0.030). No
      significant associations were observed between development of intralesional MA
      and any other morphologic or visual function measure. CONCLUSIONS: Macular
      atrophy frequently develops within an nAMD lesion in eyes receiving anti-VEGF
      therapy over 2 years. No associations between incident MA and drug or treatment
      frequency or visual function were detected, providing some reassurance to
      clinicians; however, the longer-term effects remain unknown.

PMID- 30301556
TI  - Blood pressure targeting by partial REBOA is possible in severe hemorrhagic shock
      in pigs and produces less circulatory, metabolic and inflammatory sequelae than
      total REBOA.
AB  - BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is
      an effective adjunct in exsanguinating torso hemorrhage, but causes ischemic
      injury to distal organs. The aim was to investigate whether blood pressure
      targeting by partial REBOA (pREBOA) is possible in porcine severe hemorrhagic
      shock and to compare pREBOA and total REBOA (tREBOA) regarding hemodynamic,
      metabolic and inflammatory effects. METHODS: Eighteen anesthetized pigs were
      exposed to induced controlled hemorrhage to a systolic blood pressure (SBP) of 50
      mmHg and randomized into three groups of thoracic REBOA: 30 min of pREBOA (target
      SBP 80-100 mmHg), tREBOA, and control. They were then resuscitated by autologous
      transfusion and monitored for 3 h. Hemodynamics, blood gases, mesenteric blood
      flow, intraperitoneal metabolites, organ damage markers, histopathology from the
      small bowel, and inflammatory markers were analyzed. RESULTS: Severe hemorrhagic
      shock was induced in all groups. In pREBOA the targeted blood pressure was
      reached. The mesenteric blood flow was sustained in pREBOA, while it was
      completely obstructed in tREBOA. Arterial pH was lower, and lactate and troponin
      levels were significantly higher in tREBOA than in pREBOA and controls during the
      reperfusion period. Intraperitoneal metabolites, the cytokine response and
      histological analyses from the small bowel were most affected in the tREBOA
      compared to the pREBOA and control groups. CONCLUSION: Partial REBOA allows blood
      pressure titration while maintaining perfusion to distal organs, and reduces the
      ischemic burden in a state of severe hemorrhagic shock. Partial REBOA may lower
      the risks of post-resuscitation metabolic and inflammatory impacts, and organ
      dysfunction.

PMID- 30301557
TI  - Beyond the pillars of the ankle: A prospective randomized CT analysis of
      syndesmosis' injuries in Weber B and C type fractures.
AB  - BACKGROUND: This study compared clinical and radiographic results of patients who
      underwent stabilization of syndesmosis with one tricortical syndesmotic screw
      divided into three different groups: Group A without preoperative fractured ankle
      computed tomography (CT) scan, Group B with preoperative fractured CT scan, and
      Group C with preoperative bilateral ankle CT analysis. METHODS: Between June 2016
      and May 2017, fifty-one patients with fracture type AO/OTA 44 B and C were
      analyzed. Of those, 14 (27.45%) were assigned to Group A, 19 (37.25%) to Group B,
      and 18 (35.30%) to Group C. Clinical outcomes with AOFAS score at 3, 6 and 12
      months were recorded. Seven measurements on axial CT scan images were confronted
      between the injured and uninjured ankle to check the accuracy of reduction.
      RESULTS: At three months of follow up the median AOFAS score was 70.86 +/- 2.98
      with no significative difference between groups (p = 0.105). At 12 months of
      follow up the median AOFAS score was higher in group C (93.44 +/- 3.01) compared
      to Group B and Group C. The seven variables measured at the CT scan after
      syndesmotic reduction were statistically different between groups. We found a
      better restoration of the tibiofibular distances and the correct ankle anatomy in
      Group C respect to Group A and Group B. CONCLUSIONS: Use of the pre-operative CT
      scan of the injured and uninjured ankle give to the surgeons the more and
      accurate information for the reduction and help him intraoperative in the correct
      maneuvers. The accuracy of the syndesmosis reduction determines better clinical
      outcomes.

PMID- 30301558
TI  - Sleep problems and suicide risk in youth: A systematic review, developmental
      framework, and implications for hospital treatment.
AB  - OBJECTIVE: Sleep problems are transdiagnostic symptoms that confer significant
      risk for suicidal thoughts and behaviors (STBs) in adults. However, less is known
      about the sleep-STB association in adolescence-a developmental period when rates
      of STBs increase drastically, and sleep problems may be particularly pernicious.
      This article provides a systematic review of research on the sleep-STB
      association in youth, an overview of changes in sleep regulation during
      adolescence that may make sleep problems particularly detrimental for youth, and
      a discussion of the clinical implications of the sleep-STB association for
      hospitalized youth. METHOD: The systematic review included all longitudinal
      studies in which sleep problems were examined as prospective predictors of STBs
      in adolescents (aged 10-24 years). The search was conducted on December 1, 2017
      using PsychINFO, PubMed, and Web of Science databases. RESULTS: Ten studies
      qualified for inclusion in this review. Of these, seven studies found at least
      one type of sleep problem significantly predicted a STB outcome. CONCLUSIONS:
      Although findings are mixed, growing research suggests that sleep problems may be
      a unique risk factor for STBs in youth. Sleep problems may be particularly
      important intervention target because they are easily assessed across healthcare
      settings and are amenable to treatment.

PMID- 30301559
TI  - External validation of a multifactorial normal tissue complication probability
      model for tube feeding dependence at 6 months after definitive radiotherapy for
      head and neck cancer.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to externally validate a
      previously published normal tissue complication probability (NTCP) model for tube
      feeding dependence at 6 months (TUBEM6) after completion of (chemo) radiotherapy.
      MATERIALS AND METHODS: This study evaluated 122 head and neck cancer patients
      treated by definitive (chemo) radiotherapy. The closed testing procedure was used
      to select the appropriate method for updating the NTCP model. In this procedure,
      the likelihood ratio test was used to compare the updated model against the
      original model. RESULTS: Mean predicted NTCP was 12.2% (95% CI: 9.9%-14.5%) when
      using the original NTCP model for TUBEM6. TUBEM6 at our institute was 5.7% (95%
      CI: 1.8-9.6%) for the 122 patients evaluated. The test for the model revision
      against the original NTCP model was statistically significant (p = 0.032). The
      test for the model revision against the model adjusting intercept only was not
      statistically significant (p = 0.240). According to the closed testing procedure,
      the model required adjusting the intercept only. CONCLUSIONS: TUBEM6 at our
      institute was lower than that predicted by the original NTCP model. The closed
      testing procedure indicated that only an adjustment of the intercept was needed
      indicating the importance of external validation.

PMID- 30301560
TI  - Evaluating class III antiarrhythmic agents as novel MYC targeting drugs in
      ovarian cancer.
AB  - OBJECTIVE: To evaluate the utility of amiodarone and its derivative dronedarone
      as novel drug repositioning candidates in EOC and to determine the potential
      pathways targeted by these drugs. METHODS: Drug-predict bioinformatics platform
      was used to assess the utility of amiodarone as a novel drug-repurposing
      candidate in EOC. EOC cells were treated with amiodarone and dronedarone. Cell
      death was assessed by Annexin V staining. Cell viability and cell survival were
      assessed by MTT and clonogenics assays respectively. c-MYC and mTOR/Akt axis were
      evaluated as potential targets. Effect on autophagy was determined by autophagy
      flux flow cytometry. RESULTS: "DrugPredict" bioinformatics platform ranked Class
      III antiarrhythmic drug amiodarone within the top 3.9% of potential EOC drug
      repositioning candidates which was comparable to carboplatin ranking in the top
      3.7%. Amiodarone and dronedarone were the only Class III antiarrhythmic drugs
      that decreased the cellular survival of both cisplatin-sensitive and cisplatin
      resistant primary EOC cells. Interestingly, both drugs induced degradation of c
      MYC protein and decreased the expression of known transcriptional targets of c
      MYC. Furthermore, stable overexpression of non-degradable c-MYC partially rescued
      the effects of amiodarone and dronedarone induced cell death. Dronedarone induced
      higher autophagy flux in EOC cells as compared to amiodarone with decreased
      phospho-AKT and phospho-4EBP1 protein expression, suggesting autophagy induction
      due to inhibition of AKT/mTOR axis with these drugs. Lastly, both drugs also
      inhibited the survival of EOC tumor-initiating cells (TICs). CONCLUSIONS: We
      provide the first evidence of class III antiarrhythmic agents as novel c-MYC
      targeting drugs and autophagy inducers in EOC. Since c-MYC is amplified in >40%
      ovarian tumors, our results provide the basis for repositioning amiodarone and
      dronedarone as novel c-MYC targeting drugs in EOC with potential extension to
      other cancers.

PMID- 30301562
TI  - Pericardial effusion in infective endocarditis: The times they are a-changin'.

PMID- 30301561
TI  - Too many women are dying from cervix cancer: Problems and solutions.
AB  - One woman dies from cervix cancer every 2 min, adding up to over 270,000 deaths
      globally per year. This cancer affects a young population, and hence, the loss of
      life is staggering. There are many aspects of prevention, screening, and care
      that are suboptimal. A great deal is known about HPV induced carcinogenesis, yet
      clinical outcomes have been stagnant over decades. There has been no improvement
      in cervix cancer survival in the US since the mid-1970s [1]. With increased
      knowledge of the disease and greater worldwide resources including prevention,
      screening, and improved therapeutics, there is significant promise for fewer
      women to die from this virally induced cancer. We focus here on the major
      problems in prevention, screening, and delivery of care for cervix cancer and
      provide concrete solutions. With appropriate focus, a major improvement in
      survival from cervix cancer could be achieved in a short time span.

PMID- 30301564
TI  - Heart valve involvement in antiphospholipid syndrome: More than you think!

PMID- 30301563
TI  - Hyperbaric oxygen boosts long noncoding RNA MALAT1 exosome secretion to suppress
      microRNA-92a expression in therapeutic angiogenesis.
AB  - BACKGROUND: Hyperbaric oxygen (HBO) could improve wound healing by enhancement of
      angiogenesis. The effect of HBO on metastasis-associated lung adenocarcinoma
      transcript 1 (MALAT1), a proangiogenic long noncoding RNA, and on endothelial
      cell-derived exosome is unknown. We aim to investigate both whether MALAT1 is
      altered in human coronary artery endothelial cells (HCAECs)-derived exosomes in
      response to HBO as well as the molecular regulatory mechanisms of MALAT1 in
      HCAECs under HBO treatment. METHODS AND RESULTS: HCAECs were cultured and HBO was
      applied at 2.5 atmosphere absolute (ATA) in a hyperbaric chamber. Exosomes were
      extracted from culture media. A rat model of hind-limb ischemia was performed by
      ligation of the right femoral artery. HBO at 2.5 ATA significantly increased
      MALAT1 expression in HCAECs and HCAECs-derived exosomes. MALAT1 suppressed miR
      92a expression in HCAEC-derived exosomes under HBO. Silencing MALAT1 by MALAT1
      siRNA significantly inhibited KLF2 mRNA expression induced by HBO, as did MiR
      92a. MiR-92a significantly decreased KLF2 luciferase activity in HCAECs under
      HBO. HBO and HBO-induced exosomes significantly increased cell proliferation and
      the capillary-like network formation of HCAECs. MALAT1 siRNA and miR-92a
      overexpression significantly attenuated the cell proliferation and tube formation
      caused by HBO-induced exosome. HBO and HBO-induced exosomes significantly
      improved neovascularization in a rat model of hind-limb ischemia. CONCLUSIONS:
      HBO upregulates MALAT1 to suppress miR-92a expression and counteracts the
      inhibitory effect of miR-92a on KLF2 expression in HCAECs to enhance
      neovascularization. HBO-induced derivation of exosomes from HCAECs enhances
      angiogenesis. Exosomes containing MALAT1 might serve as a valuable therapeutic
      tool for neovascularization by HBO.

PMID- 30301565
TI  - Desperation Oncology.

PMID- 30301566
TI  - Epilepsy surgery: A therapeutic patient education program.
AB  - Before the creation of a therapeutic patient education (TPE) program for epilepsy
      surgery, a needs analysis was conducted with 29 people, including patients
      (n=13), family members (n=9) and healthcare providers (n=7). Most of them
      highlighted the psychological difficulties of the surgical process, and the need
      for considerably more precise information concerning the immediate postoperative
      period. In addition, several patients and/or family members requested meeting
      with a patient who had undergone the surgery. The majority of subjects were
      interested in epilepsy-surgery TPE. These data were important in the creation of
      our TPE program and, more generally, for the management of these patients.

PMID- 30301567
TI  - Corrigendum to "Vascular brain-derived neurotrophic factor pathway in rats with
      adjuvant-induced arthritis: Effect of anti-rheumatic drugs" [Atherosclerosis 274
      (July 2018) 77-85].

PMID- 30301569
TI  - [Sexual violence against women in Tunisia].
AB  - BACKGROUND: Sexual violence exists everywhere in the world. It depends mainly on
      the cultural and religious norms conveyed in the various societies. This is a
      neglected area of research. Available data are insufficient, especially in Arab
      Muslim context. METHODS: In this paper, we comprehensively review the scientific
      literature in order to clarify the cultural, religious and legal aspects of the
      concept of sexual violence against women in Tunisia, and ask the question of the
      urgent need to put in place strategies to counter this problem. RESULTS: The
      National Office for Family and Population published in 2011 the results of the
      national survey on violence against women in Tunisia, including data on sexual
      violence and its impact on women's health and well-being. According to this
      survey, 14.2% of women reported having been sexually abused by an intimate
      partner during their lifetime and 9.0% reported having experienced it during the
      last 12 months. One out of every six Tunisian women has been the victim of a
      sexual violence in a conjugal setting. More men than women legitimized violence
      against women in contexts where family control, especially conjugal control, is
      exercised over them. In a study examining the impact of culture and religion on
      experiences and sexual practice of women in Tunisian society, the majority of
      respondents thought that sexuality in women was a religious duty and that they do
      not have the right to refuse their husbands or to rebel. Thus, women would be
      doubly sanctioned having neither the right to express their desire nor not to
      respond to their husband's desire. A survey of a representative sample of
      Tunisian women found that 56.9% of the participants reported being victims of
      domestic violence, particularly sexual violence (10.7%) consisting mainly of rape
      and sodomy, at least once in their lifetime. This survey showed that those
      victims expressed dissatisfaction with overall quality of life. Moreover,
      contrary to Western literature, sexual violence was the least reported form of
      violence by teenage girls in Tunisian schools. Indeed, cultural values of
      modesty, virginity and honor are socially much more demanded for girls, in Arab
      countries in general, reinforcing staggering silence and inaction around violence
      experienced by school-aged adolescents. In Tunisian society, the cultural
      "solution" to rape wants the woman to marry her rapist which safeguards her
      family's integrity by legitimizing the union. CONCLUSION: Sexual violence has
      detrimental effects on female victims' physical and mental health. Even if the
      information on this form of violence is not easy to obtain in our environment,
      and that rates of subjects reporting sexual violence in their lifetimes are not
      important, the problem of sexual violence must be considered as a public health
      problem requiring urgent interventions and a greater institutional will.

PMID- 30301568
TI  - Hydroxypropyl-beta-cyclodextrin protects from kidney disease in experimental
      Alport syndrome and focal segmental glomerulosclerosis.
AB  - Studies suggest that altered renal lipid metabolism plays a role in the
      pathogenesis of diabetic kidney disease and that genetic or pharmacological
      induction of cholesterol efflux protects from the development of diabetic kidney
      disease and focal segmental glomerulosclerosis (FSGS). Here we tested whether
      altered lipid metabolism contributes to renal failure in the Col4a3 knockout
      mouse model for Alport Syndrome. There was an eight-fold increase in the
      cholesterol content in renal cortexes of mice with Alport Syndrome. This was
      associated with increased glomerular lipid droplets and cholesterol crystals.
      Treatment of mice with Alport Syndrome with hydroxypropyl-beta-cyclodextrin
      (HPbetaCD) reduced cholesterol content in the kidneys of mice with Alport
      Syndrome and protected from the development of albuminuria, renal failure,
      inflammation and tubulointerstitial fibrosis. Cholesterol efflux and trafficking
      related genes were primarily affected in mice with Alport Syndrome and were
      differentially regulated in the kidney cortex and isolated glomeruli. HPbetaCD
      also protected from proteinuria and mesangial expansion in a second model of non
      metabolic kidney disease, adriamycin-induced nephropathy. Consistent with our
      experimental findings, microarray analysis confirmed dysregulation of several
      lipid-related genes in glomeruli isolated from kidney biopsies of patients with
      primary FSGS enrolled in the NEPTUNE study. Thus, lipid dysmetabolism occurs in
      non-metabolic glomerular disorders such as Alport Syndrome and FSGS, and HPbetaCD
      improves renal function in experimental Alport Syndrome and FSGS.

PMID- 30301570
TI  - Non-nucleoside reverse transcriptase inhibitors (NNRTIs)-induced Stevens-Johnson
      syndrome and gynecomastia in an HIV-infected child: A case report.
AB  - BACKGROUND: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are
      antiretroviral drugs often used in the first-line treatment regimen of HIV1
      infection worldwide. We report a case of successive gynecomastia and Stevens
      Johnson syndrome (SJS) respectively induced by efavirenz and nevirapine in a
      single patient. CASE REPORT: A 16-year-old boy, HIV1-infected since birth, was
      started on antiretroviral treatment (ART) in August 2015 and was taking a regimen
      comprising abacavir, lamivudine and efavirenz. In April 2016, when his weight
      reached 35kg, abacavir was replaced with tenofovir. Bilateral breast enlargement,
      previously hidden by the patient, was diagnosed two years after the start of ART.
      History-taking, physical examination and laboratory tests ruled out known causes
      of gynecomastia, and efavirenz was thus considered the most likely cause. This
      drug was then withdrawn and replaced with nevirapine in July 2017. Thirty-three
      days after the patient started nevirapine treatment, a skin rash appeared.
      Physical examination revealed erythematous macules and flaccid bullae with
      estimated skin detachment of 10%. There were also conjunctival, buccal and
      genital lesions. A diagnosis was made of SJS induced by nevirapine. Three months
      after withdrawal of efavirenz, breast size decreased by 3cm on the left breast
      and 2cm on the right breast; two months after the SJS, cutaneous sequelae alone
      persisted, such as diffuse hyperchromic macules. DISCUSSION: Recognition of
      gynecomastia as a side-effect of efavirenz is important to allow the condition to
      be treated while it is still potentially reversible. Moreover, when efavirenz is
      replaced, a protease inhibitor should be preferred to nevirapine.

PMID- 30301571
TI  - Deep Learning with Microfluidics for Biotechnology.
AB  - Advances in high-throughput and multiplexed microfluidics have rewarded
      biotechnology researchers with vast amounts of data but not necessarily the
      ability to analyze complex data effectively. Over the past few years, deep
      artificial neural networks (ANNs) leveraging modern graphics processing units
      (GPUs) have enabled the rapid analysis of structured input data - sequences,
      images, videos - to predict complex outputs with unprecedented accuracy. While
      there have been early successes in flow cytometry, for example, the extensive
      potential of pairing microfluidics (to acquire data) and deep learning (to
      analyze data) to tackle biotechnology challenges remains largely untapped. Here
      we provide a roadmap to integrating deep learning and microfluidics in
      biotechnology laboratories that matches computational architectures to problem
      types, and provide an outlook on emerging opportunities.

PMID- 30301572
TI  - Current Bottlenecks and Challenges of the Microalgal Biorefinery.
AB  - Microalgae are increasingly considered as sources of renewable feedstocks for
      industrial production, and microalgae production now focuses on the multiproduct
      microalgal biorefinery. However, such a biorefinery presents several bottlenecks
      that are mainly associated with downstream processes. This reduced downstream
      efficiency results from unsolved problems related to the culture strategy for the
      accumulation of different products - the protein versus lipid dilemma - and the
      dilute nature of the microalgal culture. We identify new trends and propose
      promising solutions for realizing microalgal biorefineries at industrial scale.
      New perspectives and challenges are identified in protein properties and in the
      integration and cooptimization of culture and downstream processes.

PMID- 30301574
TI  - Direct Anterior Approach and Perioperative Fracture With a Single-Taper Wedge
      Femoral Component.
AB  - BACKGROUND: Despite growing interest in direct anterior approach total hip
      arthroplasty, perioperative femoral fracture and early aseptic loosening are
      increasingly recognized complications. Previous research has documented the role
      of surgeon experience in association with these femoral complications. The
      purpose of this study was to explore the relationship between femoral component
      design and early periprosthetic femoral complications. METHODS: This was an
      extension of previous work with an updated patient cohort of 5090 consecutive
      direct anterior primary total hip arthroplasties at a single institution with a
      single-taper, wedge femoral stem comprising 4 variants involving length and
      geometry: group 1, full-length, standard profile; group 2, full-length, reduced
      distal profile; group 3, short-length, standard profile; and group 4, short
      length, reduced distal profile. Records were reviewed retrospectively for the
      incidence of early postoperative periprosthetic fracture or aseptic loosening and
      analyzed with regard to patient demographics and femoral stem type. RESULTS:
      There were 42 (0.83%) periprosthetic femur complications observed in the early
      postoperative period. Increased age (P < .001) and female gender (P = .023) were
      significantly associated with incidence of femoral complications in univariate
      analysis, while age maintained this significant relationship in multivariate
      analysis (P < .001). There was a trend toward increased complication rate in
      patients receiving a short stem with full profile taper (1.27%, P = .0539).
      CONCLUSION: Despite an overall low rate of femoral complications after direct
      anterior total hip arthroplasty, the risk is increased in elderly patients and
      females. Furthermore, femoral stem design may portend an elevated risk of these
      complications.

PMID- 30301573
TI  - Optimal contrast-enhanced MRI image thresholding for accurate prediction of
      ventricular tachycardia using ex-vivo high resolution models.
AB  - Patient specific models created from contrast-enhanced (i.e. late-gadolinium,
      LGE) MRI images can be used for prediction of reentry location and clinical
      ablation planning. However, there is still a need for direct and systematic
      comparison between characteristics of ventricular tachycardia (VT) morphologies
      predicted in computational models and those acquired in clinical or experimental
      protocols. In this study, we aimed to: 1) assess the differences in VT
      morphologies predicted by modeling and recorded in experiments in terms of
      patterns and location of reentries, earliest and latest activation sites, and
      cycle lengths; and 2) define the optimal range of infarct tissue threshold values
      which provide best match between simulation and experimental results. To achieve
      these goals, we utilized LGE-MRI images from 4 swine hearts with inducible
      monomorphic VT. The images were segmented to identify non-infarcted myocardium,
      semi viable gray zone (GZ), and core scar based on pixel intensity. Several
      models were reconstructed from each LGE-MRI scan, with voxels of intensity
      between that of non-infarcted myocardium and 20-50% of the maximum intensity (in
      10% increments) in the infarct region classified as GZ. VT induction was
      simulated in each model. Our simulation results showed that using GZ intensity
      thresholds of 20% or 30% resulted in the best match of simulated propagation
      patterns and reentry locations with those from the experiment. Overall, we
      matched 70% (7/10) morphologies for all the hearts. Our simulation shows that MRI
      based computational models of hearts with myocardial infarction can accurately
      reproduce the majority of experimentally recorded post-infarction VTs.

PMID- 30301575
TI  - An Innovative Ultrasound Strain Elastographic Method for the Differential
      Diagnosis of Breast Tumors.
AB  - In this monocentric perspective study examining 64 lesions (19 benign and 45
      malignant), we tested an innovative ultrasound elastographic method for
      diagnosing breast tumors. A new region of control and a new index designating the
      strain ratio (SR) were used. A traditional ultrasound elastographic method was
      used as the control. The results indicated that the SR ratios of the benign and
      malignant groups were 0.25 +/- 0.22 and 1.10 +/- 1.53, respectively, and this
      difference was statistically significant. The area under the receiver operating
      characteristic curve of the SR ratio method was 0.95, the cutoff point was 0.37
      and the sensitivity and specificity were 95.56% and 94.74%, respectively. The two
      receiver operating characteristic curves of the traditional method and the SR of
      the proposed method were significantly different, at a p value of 0.02. Compared
      with that of the traditional method, the SR obtained with the new method had a
      larger area under the receiver operating characteristic curve, sensitivity,
      specificity and objectivity.

PMID- 30301576
TI  - Mutation analysis of KIF5A in Chinese amyotrophic lateral sclerosis patients.
AB  - Amyotrophic lateral sclerosis (ALS) is an age-related fatal neurodegenerative
      orphan disorder that is characterized by progressive injury of both the upper and
      lower motor neurons. Recently, loss-of-function mutations predominately
      disrupting the C-terminal amino acid sequence of KIF5A via aberrant exon 27
      splicing have been reported in European ALS cohorts. However, the contributions
      of KIF5A mutations in Asian patients with ALS remain unclear. KIF5A sequences,
      including exons 26 and 27, were analyzed in a large Chinese ALS cohort comprising
      33 unrelated familial ALS probands, 645 sporadic ALS (SALS) patients, 15 ALS
      patients presenting with concomitant frontotemporal dementia, 400 in-house
      controls, and 12,951 East Asian individuals from the Exome Aggregation Consortium
      and Genome Aggregation Database databases. As a result, the previously reported
      canonical splicing site mutation c.2993-1G>A was found in 1 SALS patient, while
      no mutations were detected in familial ALS case or ALS patients presenting with
      concomitant frontotemporal dementia. The frequency of KIF5A mutations accounts
      for 0.16% (1/645) of Chinese SALS patients, implying that it is an uncommon
      genetic determinant of ALS in Chinese patients.

PMID- 30301577
TI  - Productive activities of the older people in Vietnam.
AB  - Productive activities are crucial factors leading to an "active aging"
      population. With the case of Vietnam, this paper aimed to explore the productive
      activities among Vietnamese older people by using data from the Vietnam Aging
      Survey (VNAS), which was conducted in 2011 as the first-ever nationally
      representative survey on persons aged 50 and over in Vietnam and contained 2789
      older people (those aged 60 and over) representing all older people living in 6
      ecological regions and urban and rural areas in Vietnam. Productive activities
      included working and/or taking care of any (great)grandchild(ren) in the past 12
      months prior to the survey. Using paired t-tests and probit models, we compared
      the differences in these productive activities among older people in terms of sex
      and living area. The results from various t-tests showed that educational
      attainment, health status and poverty status were key factors differentiating
      older men and women and rural and urban older people in these productive
      activities. For the probit estimations in terms of both gender and living
      location, the results indicated that age, education, health status and supportive
      children were determinants of working decision, while age, marital status and
      size of household were consistently important factors of taking care of
      (great)grandchildren. The paper also discussed policy implications for socio
      economic and health protection in promoting older people's productive activities
      as well as protecting them from a variety of risks and vulnerabilities.

PMID- 30301578
TI  - Cross-cultural Adaptation and Validation of the Greek Voice Handicap Index-10
      (GVHI-10) With Additional Receiver Operating Characteristic Analysis.
AB  - OBJECTIVE(S): The use of subjective evaluation tools are proven useful and of
      high clinical value in the case of voice disordered population. For that type of
      evaluation, self-assessment questionnaires about the severity of the voice like
      Voice Handicap Index-30 (VHI-30) have been developed. The VHI-30 is the most
      studied tool which includes psychometrically robustness while guiding physician's
      therapeutic decision making. Additionally, a valid abbreviated version of VHI-30
      was developed for the first time in the Greek Language which is named as Greek
      Voice Handicap Index-10 (GVHI-10). Consequently, the aim of our study was to
      validate the proposed version of the VHI-10. METHODS: Ninety nondysphonic
      individuals and 90 dysphonic patients were classified by Otolaryngologists and
      Speech Language Pathologists. The study's subjects were evaluated with endoscopy
      and stroboscopy. Also, they were administrated the GVHI-30 and the translated
      version of the Voice Evaluation Template (VEF). The GVHI-10 was extracted by the
      Greek version of VHI-30. RESULTS: The group with voice disorders exhibited higher
      statistical significance in all GVHI-10 scores compared to those of the control
      group. The GVHI-10 showed a high internal consistency (Cronbach's a = 0.915 and
      split-half reliability coefficient equal to 0.86), good sensitivity compared to
      Greek VHI-30 (r = 0.764, P = 0.000) and intraclass correlation. A total cut-off
      point equal to 6.50 (AUC: 0.964; P < 0.001) was also calculated. CONCLUSIONS: The
      proposed version of GVHI-10 distinguished the perceived levels of voice between
      dysphonic and nondysphonic groups and between different voice disordered
      populations. The GVHI-10 is shown to be clinically valid and sensitive exhibiting
      high reliability.

PMID- 30301579
TI  - Epigenome-wide association study of peripheral blood mononuclear cells in
      systemic lupus erythematosus: Identifying DNA methylation signatures associated
      with interferon-related genes based on ethnicity and SLEDAI.
AB  - Systemic lupus erythematosus (SLE or lupus) is a heterogeneous autoimmune disease
      characterized by the involvement of multiple organs and the production of
      antinuclear antibodies. DNA methylation plays an important role in the
      pathogenesis of lupus. We have performed an epigenome-wide DNA methylation study
      in lupus and healthy control (non-lupus) subjects to identify epigenetic patterns
      in lupus characterized ethnicity and SLE disease activity index (SLEDAI). A total
      of fifty-seven lupus patients (39 African American (AA) and 18 European American
      (EA)) and 33 healthy controls (17 AA and 16 EA) were studied. Differential DNA
      methylation between lupus patients and controls was assessed for approximately
      485,000 CpG sites across the genome. We identified 41 differentially methylated
      sites (associated with 30 genes) between lupus and control s subjects, 85% of
      which were hypomethylated. Significant hypomethylation of differentially
      methylated sites was associated with several interferon-related genes, including
      MX1, IFI44L, PARP9, DT3XL, IFIT1, IFI44, RSAD2, PLSCR1, and IRF7. Several of
      these associated genes were also hypomethylated in comparisons between AA lupus
      and AA non-lupus subjects and between lupus patients with SLEDAI>6 and non-lupus
      subjects. Our analysis of gene expression data through RT-PCR confirmed these
      findings. Thus, the results indicate epigenetics susceptibility in lupus, which
      may be associated with SLEDAI score and ethnicity. In addition, our findings
      support the importance of the Type 1 interferon pathway in lupus pathogenesis.

PMID- 30301580
TI  - Quality gaps and priorities for improvement of healthcare service for patients
      with prolonged mechanical ventilation in the view of family.
AB  - BACKGROUND: Little is known about the gaps between expectation and the perception
      of service quality in the care setting of prolonged mechanical ventilation (MV).
      METHODS: We conducted this prospective study at the Respiratory Care Center (RCC)
      of a medical center from February 2017 to January 2018. Family members of the
      patients admitted to the RCC completed a questionnaire based on the SERVQUAL
      instrument in two sections - expectation and perception, consisting of 22
      questions each in five dimensions. We analyzed the gaps between paired items,
      used important-performance analysis (IPA) to identify priority items for
      improvement, and performed multivariate logistic regression analysis. RESULTS: A
      total of 167 respondents participated in the survey. The average length of
      patient stay in the RCC was 19.4 days, and 70.7% were successfully liberated from
      MV. The overall mean SERVQUAL scores for the two sections were similar (4.50 +/-
      0.52 and 4.51 +/- 0.54 for expectation and perception, respectively; p = 0.808).
      IPA identified four items, including one "tangible," one "reliability" and two
      "empathy" with an undesired expectation/perception gap indicating a priority for
      improvement. Multivariate logistic regression analysis showed that male
      respondents, patients older than 75 years, tracheostomy, and the need for
      physical training or dialysis were associated with an increased gap in these
      priority items. CONCLUSION: Gaps exist between expectation and perception in
      multiple dimensions of the quality of healthcare service in the care setting of
      prolonged MV, indicating unmet needs and priorities for improvement.

PMID- 30301581
TI  - The choice of antiviral therapy for hepatitis C recurrence after liver
      transplantation in the real world.

PMID- 30301582
TI  - Perspectives on window of opportunity trials in head and neck cancer: lessons
      from the EORTC 90111-24111-NOCI-HNCG study.
AB  - Assessing tumour response using a traditional phase I, II and III trial approach
      is not without limitations, particularly when targeted therapies are involved.
      Window of opportunity trials, performed presurgically but differing from
      neoadjuvant studies, were developed in an attempt to overcome the limitations of
      the traditional approach. A recent window of opportunity trial, the EORTC 90111
      24111-NOCI-HNCG study, evaluated afatinib in treatment-naive patients with
      squamous cell carcinoma of the head and neck. While this study was the first to
      demonstrate the activity of afatinib in this setting and to define its potential
      predictive biomarkers, it also highlighted the challenges associated with the
      window of opportunity trial design, including the impact of patient selection,
      tumour site, and other organisational issues. This report details the key
      learnings from the EORTC 90111-24111-NOCI-HNCG study and provides recommendations
      to overcome the challenges of this particular trial design.

PMID- 30301583
TI  - Vaccination Status and Another Preventive Measures in Medical Schools. Big Needs
      and Opportunities.

PMID- 30301584
TI  - Emergency Medical Services Utilization and Outcomes of Patients with ST-Elevation
      Myocardial Infarction in Lebanon.
AB  - BACKGROUND: Arrival of patients with ST-elevation myocardial infarction (STEMI)
      by Emergency Medical Services (EMS) results in shorter reperfusion times and
      lower mortality in developed countries. OBJECTIVES: This study examines EMS use
      by STEMI patients in Lebanon and associated clinical outcomes. METHODS: A
      retrospective observational study with chart review was carried out for STEMI
      patients arriving to the Emergency Department of a tertiary care center in
      Lebanon between January 1, 2013 and August 31, 2016. A descriptive analysis was
      done and followed by a bivariate analysis comparing two groups of patients (EMS
      vs. Non-EMS). RESULTS: A total of 280 patients were included in the study. They
      were mostly male (71.8%). Mean age was 65.1 years (95% confidence interval [CI]
      63.4-66.9). Only 12.5% (95% CI 8.6-16.4) presented by EMS. Chest pain (81.1%) was
      the most common presenting symptom. Anterior myocardial infarction was the most
      common electrocardiogram (ECG) diagnosis (51.4%). Most patients were admitted
      (98.2%), and 72.0% of these patients were treated with primary percutaneous
      coronary intervention. Cardiogenic shock was the most frequent in-hospital
      complication (6.2%). The mortality rate was 7.1%. Mean door-to-ECG and door-to
      balloon times were 10.8 (95% CI 7.1-14.4) min and 106.2 (95% CI 95.9-116.6) min,
      respectively. Patients' characteristics, presenting symptoms, outcomes, and
      performance metrics were similar between the two groups. CONCLUSION: EMS is
      underutilized by STEMI patients in Lebanon and is not associated with improvement
      in clinical outcomes. Medical oversight and quality initiatives focusing on
      outcomes of patients with timely sensitive emergencies are needed to advance the
      prehospital care system in Lebanon.

PMID- 30301585
TI  - A Cost-Effective, Rapidly Constructed Simulation Model for Ultrasound-Guided
      Pericardiocentesis Procedural Training.
AB  - BACKGROUND: Emergent ultrasound-guided pericardiocentesis (USGP) is an uncommonly
      performed procedure by emergency physicians (EPs). USGP simulation models have
      previously been developed to increase procedural proficiency, but these models
      are limited for routine implementation secondary to high-cost, lengthy time to
      construct, and lack of durability. The objective of this study was to develop an
      USGP simulation model that is cost-effective, easily and rapidly constructed, and
      has procedure-specific fidelity. DISCUSSION: We have developed a novel tofu
      simulation model for USGP training. The model cost per unit was $1.81 and the
      average construction time was 2.5 +/- 0.3 min. The model can withstand upward of
      100 needle punctures. Our model provides USGP procedure-specific aspiration of a
      simulated pericardial effusion. CONCLUSIONS: The tofu USGP model provides a cost
      effective and rapidly constructible simulation tool that could be readily
      integrated in EP procedural training.

PMID- 30301586
TI  - [A sternal mass].

PMID- 30301587
TI  - The effect of a multidisciplinary approach on geriatric hip fractures in Japan.
AB  - BACKGROUND: This study aimed to report results of the multidisciplinary treatment
      approach for geriatric hip fractures and evaluate its effectiveness compared with
      conventional treatment. Patients aged 65 years and older who presented with a hip
      fracture at our hospital on or after 2014 were treated according to a
      multidisciplinary approach. METHOD: Two groups of patients with hip fracture were
      compared. Group I (n = 364) was treated according to the new multidisciplinary
      approach in 2014-2016, and Group II (n = 105) which received conventional
      treatment in 2012. Time to surgery, length of hospital stay, postoperative
      complications, osteoporosis treatment, functional recovery, in-hospital
      mortality, 90-day mortality, and 1-year mortality were evaluated. The medical
      costs of multidisciplinary treatment were compared with those in other hospitals
      every year. RESULTS: There were no significant differences in the time to surgery
      between Group I and Group II, but each was considerably shorter than the average
      time in other Japanese hospitals. The length of hospital stay was longer in Group
      I. The overall postoperative complication rate was lower in Group I, but there
      was no significant difference for each individual complication. The rate of anti
      osteoporosis pharmacotherapy administration at the time of discharge was
      significantly higher in Group I. Moreover, the proportion of patients who
      recovered to their pre-injury functional level was significantly higher in Group
      I. The mortality rates did not significantly differ year on year. The total
      hospitalization medical cost per patient for the multidisciplinary treatment was
      lower than other hospital costs every year. CONCLUSIONS: Multidisciplinary
      treatment produced no significant improvement in time to surgery, length of
      hospital stay, or postoperative complications. However, the use of the
      multidisciplinary treatment approach led to a significant increase in
      osteoporosis treatment rate and better functional recovery. Furthermore, the
      total medical costs for multidisciplinary treatment were lower than the acute
      care hospital costs.

PMID- 30301588
TI  - Nerve Transfers for Enterovirus D68-Associated Acute Flaccid Myelitis: A Case
      Series.
AB  - BACKGROUND: Acute flaccid myelitis is associated with enterovirus D68 -induced
      inflammation and destruction of cervical anterior horn cells. To date, no medical
      intervention has altered the disease course. METHODS: We report two pediatric
      patients who were treated with nerve transfer in three limbs with sustained upper
      extremity neuropathy. Postoperative outcomes included muscle strength, graded on
      the British Medical Research Council (BMRC) scale, range of motion, and
      electromyography. RESULTS: Two years postoperatively, Patient 1 had improved
      elbow flexion to BMRC grade 4+, 125 degrees  of flexion, and discrete to
      decreased motor unit recruitment in targeted muscles. Twenty-one months
      postoperatively, Patient 2 demonstrated right brachialis flexion to BMRC grade
      4+/5 and deltoid firing with simultaneous pectoralis major recruitment, and
      limited but active flexor digitorum profundus flexion. CONCLUSIONS: Both patients
      continue to demonstrate functional recovery two years postoperatively. These
      outcomes suggest a promising reconstructive technique for this emerging and
      devastating viral endemic.

PMID- 30301589
TI  - Combining visual sensory functions and visuospatial orienting functions in
      children with visual pathology: A longitudinal study.
AB  - BACKGROUND: Peripheral and central visual processing development highly depends
      on the integrity of the visual sensory system and the allocation of visuospatial
      attention. METHOD: We quantitatively followed visual sensory functions (VSF) and
      visuospatial orienting functions (VOF) over two years in 77 children (1-13 years)
      with different types of visual pathology. RESULTS: Within the clinical groups,
      VSF were relatively constant over two years, except visual acuity, and VOF were
      characterized by longer reaction time, shorter fixation duration, and lower
      fixation accuracy than normal for their age. Children with peripheral pathology
      had high rates of abnormal VSF, of changes to abnormal visual acuity at 1-6
      years, and larger and more abnormal VOF (fixation inaccuracy). Children with
      central pathology had relatively good VSF, whereas two-third had delayed
      orienting reaction times that differed from other groups mainly at 1-6 years.
      CONCLUSION: The distinct patterns of quantitative VSF and VOF over time between
      the visual pathology groups, and the finding that both methods provided
      complementary information, argues for combining both types of assessments to
      provide comprehensive monitoring of visual functioning in children from a young
      age.

PMID- 30301590
TI  - Genetic analysis of undiagnosed ataxia-telangiectasia-like disorders.
AB  - OBJECTIVES: Defects in DNA damage responses or repair mechanisms cause numerous
      rare inherited diseases, referred to as "DNA-repair defects" or "DNA damage
      deficiency", characterized by neurodegeneration, immunodeficiency, and/or cancer
      predisposition. Early accurate diagnosis is important for informing appropriate
      clinical management; however, diagnosis is frequently challenging and can be
      delayed, due to phenotypic heterogeneity. Comprehensive genomic analysis could
      overcome this disadvantage. The objectives of this study were to determine the
      prevalence of ataxia-telangiectasia (A-T) and A-T-like DNA-repair defects in
      Japan and to determine the utility of comprehensive genetic testing of
      presumptively diagnosed patients in facilitating early diagnosis. METHODS: A
      nationwide survey of diseases presumably caused by DNA-repair defects, including
      A-T, was performed. Additionally, comprehensive next-generation sequencing (NGS)
      analysis, targeting known disease-causing genes, was conducted. RESULTS: Sixty
      three patients with A-T or other diseases with characteristics of DNA-repair
      defects were identified. Thirty-four patients were genetically or clinically
      definitively diagnosed with A-T (n = 22) or other DNA-repair defects (n = 12).
      Genetic analysis of 17 presumptively diagnosed patients revealed one case of
      ataxia with oculomotor apraxia type 1 (AOA1); one ataxia with oculomotor apraxia
      type 2 (AOA2); two types of autosomal dominant spinocerebellar ataxia (SCA5,
      SCA29); two CACNA1A-related ataxias; one microcephaly with or without
      chorioretinopathy, lymphedema, or mental retardation (MCLMR); and one autosomal
      dominant KIF1A-related disorder with intellectual deficit, cerebellar atrophy,
      spastic paraparesis, and optic nerve atrophy. The diagnostic yield was 58.8%.
      CONCLUSION: Comprehensive genetic analysis of targeted known disease-causing
      genes by NGS is a powerful diagnostic tool for subjects with indistinguishable
      neurological phenotypes resembling DNA-repair defects.

PMID- 30301591
TI  - Science in Focus: The Microbiome and Cancer Therapy.

PMID- 30301593
TI  - Mortality and complications after treatment of acute diabetic Charcot foot.
AB  - AIMS: Charcot foot is a rare but disabling complication to diabetic neuropathy,
      and can cause permanent, limb-threatening deformities. The aim of this study was
      to investigate a population of patients a Charcot foot on a case-by-case basis,
      in order to assess the consequences of an acute Charcot foot and its
      complications. METHODS: The study was conducted a retrospective study of patients
      admitted to the Copenhagen Wound Healing Center between 1996 and 2015 with the
      diagnosis of Charcot foot (DM14.6) and diabetes mellitus type 1 or 2 (DE10.X and
      DE11.X). Physical and electronic records were used, and compared to data from the
      Danish Diabetes Registry. RESULTS: In total 392 patients were identified of which
      173 were included. There were 26% with type 1 diabetes (initial HbA1c 81.7 +/-
      21.4 mmol/mol) and 74% with type 2 diabetes (initial HbA1c 66.5 +/- 20.3
      mmol/mol). Primary off-loading was with a removable walker in 95% of the cases
      (average off-loading time 8.3 months). The 5-year mortality was 14% with a mean
      survival time of 12.7 years. There was an association between lack of compliance
      and occurrence of foot complications, as well as between having a Charcot foot
      and leaving the workforce. CONCLUSION: More patients had type 1 diabetes compared
      to the background population, and they had a higher HbA1c than the general
      population of diabetes patients. A total of 67% developed complications such as
      ulcers, while patients non-compliant to treatment did significantly worse than
      those being compliant. The 5-year mortality was low, 14%, and comparable to
      diabetes patients without Charcot foot.

PMID- 30301594
TI  - Real life evidence that impaired awareness of hypoglycemia persists for years in
      patients with type 1 diabetes.
AB  - AIMS: To determine if impaired awareness of hypoglycemia in patients with type 1
      diabetes persists over time and to assess if continuous glucose monitoring use
      was associated with improved awareness of hypoglycemia in our population.
      METHODS: Thirty-six with type 1 diabetes and impaired awareness of hypoglycemia
      who participated in studies on impaired awareness of hypoglycemia between 2009
      and 2015 were contacted to complete an online survey. The survey included the
      Cox/Clarke and Gold hypoglycemia questionnaires and questions about continuous
      glucose monitoring use. RESULTS: 23 of 36 (63%) subjects contacted completed the
      survey. (12 M, 11 F; median age 51 years, median diabetes duration 34 years). One
      had had an islet cell transplant and was excluded. Persistent impaired awareness
      of hypoglycemia was found in 19/22 (86%) using the Cox questionnaire and 18/22
      (82%) using the Gold questionnaire. Consistent use of continuous glucose
      monitoring over the last six months defined as using a device >=75% of time over
      the last 6 months was reported by 67% (12/18) and 68% (13/19) of participants
      with persistent impaired awareness of hypoglycemia as measured by Gold and Cox;
      respectively. Nineteen of the 22 participants (86%) reported severe hypoglycemia
      over the last six months. CONCLUSION: Impaired awareness of hypoglycemia
      persisted in >80% of the subjects with type 1 diabetes we studied between 2009
      and 2015. While the consistent use of continuous glucose monitoring among our
      participants was high; it did not translate into restoration of hypoglycemia
      awareness in this population. This real world data shows that severe hypoglycemia
      continues to be a frequent problem in this patient population.

PMID- 30301595
TI  - Cardiovascular effects of caffeinated beverages.
AB  - Caffeine is the world's most popular 'drug', with tea and coffee a ubiquitous
      part of daily life. As a psychoactive stimulant, there are potential concerns
      regarding adverse cardiovascular squeal. Cardiovascular conditions, encompassing
      hypertension, coronary artery disease, rhythm disorders and heart failure affect
      billions of patients worldwide. We aim to provide a patient-centered
      comprehensive review of the cardiovascular effects of caffeinated beverages as
      they pertain to various common cardiovascular conditions. We conclude that intake
      of tea and coffee, particularly in moderate doses, does not appear to be harmful
      and may even be beneficial in a range of cardiovascular conditions, including
      coronary artery disease, heart failure and arrhythmias.

PMID- 30301592
TI  - Vector Immunity and Evolutionary Ecology: The Harmonious Dissonance.
AB  - Recent scientific breakthroughs have significantly expanded our understanding of
      arthropod vector immunity. Insights in the laboratory have demonstrated how the
      immune system provides resistance to infection, and in what manner innate
      defenses protect against a microbial assault. Less understood, however, is the
      effect of biotic and abiotic factors on microbial-vector interactions and the
      impact of the immune system on arthropod populations in nature. Furthermore, the
      influence of genetic plasticity on the immune response against vector-borne
      pathogens remains mostly elusive. Herein, we discuss evolutionary forces that
      shape arthropod vector immunity. We focus on resistance, pathogenicity and
      tolerance to infection. We posit that novel scientific paradigms should emerge
      when molecular immunologists and evolutionary ecologists work together.

PMID- 30301596
TI  - Left Atrial or Left Atrial Appendage Thrombus Resolution After Adjustment of Oral
      Anticoagulant Treatment.
AB  - BACKGROUND: There are few reports about non-vitamin K antagonist oral
      anticoagulant (NOAC) treatment for resolution of left atrium (LA) or left atrial
      appendage (LAA) thrombus. LAA thrombus is an important cause of cardiogenic
      cerebral thromboembolism, and the detection rate increases due to more and more
      patients receiving catheter ablation. However, the results from NOAC use for LA
      or LAA thrombus are still unknown in real-world practice. The aim of this study
      was to discover the resolution of LA or LAA thrombus after anticoagulant
      treatment in real-world practice. METHOD: From January 2013 to December 2016, a
      total 864 patients underwent transesophageal echocardiography (TEE), and 41 cases
      of LA or LAA thrombus were detected in our hospital. Among them, a total of 22
      patients underwent follow-up TEE to detect the resolution of LA or LAA thrombus.
      RESULT: The average age of the study patients was 72.0 +/- 11years old, and 61%
      were male. The average CHA2DS2-VASc scores were 3.76 +/- 2.01 points. A total of
      22 patients underwent follow-up TEE, and 19 (86.4%) patients presented LA or LAA
      thrombus resolution. The average resolution duration was 258.47 +/- 218.17days.
      One-year all-cause mortality was 4.9%, and the incidence of ischemic stroke was
      4.9%. Most physicians favored titration of the dosage of NOAC or warfarin in real
      world practice. CONCLUSION: In real-world practice, most physicians favored
      titration of the dosage of NOAC or warfarin for LA or LAA thrombus. LA or LAA
      thrombus could exist if the patient received a reduced dose of NOAC. High
      frequency of LAA or LA thrombi could resolve, and a low incidence of ischemic
      stroke occurred after adjustment of oral anticoagulant treatment.

PMID- 30301597
TI  - Effects of irradiation with narrowband-ultraviolet B on up-regulation of
      histamine H1 receptor mRNA and induction of apoptosis in HeLa cells and nasal
      mucosa of rats.
AB  - Narrowband-ultraviolet B (NB-UVB) phototherapy is used for the treatment of
      atopic dermatitis. Previously, we reported that irradiation with 200 mJ/cm2 of
      310 nm NB-UVB suppressed phorbol-12-myristate-13-acetate (PMA)-induced up
      regulation of histamine H1 receptor (H1R) gene expression without induction of
      apoptosis in HeLa cells. However, the effect of NB-UVB irradiation on nasal
      symptoms is still unclear. Here, we show that low dose irradiation with 310 nm NB
      UVB alleviates nasal symptoms in toluene 2,4-diisocyanate (TDI)-sensitized
      allergy model rats. Irradiation with 310 nm NB-UVB suppressed PMA-induced H1R
      mRNA up-regulation in HeLa cells dose-dependently at doses of 75-200 mJ/cm2 and
      reversibly at a dose of 150 mJ/cm2 without induction of apoptosis. While, at
      doses of more than 200 mJ/cm2, irradiation with 310 nm NB-UVB induced apoptosis.
      Western blot analysis showed that the suppressive effect of NB-UVB irradiation on
      H1R gene expression was through the inhibition of ERK phosphorylation. In TDI
      sensitized rat, intranasal irradiation with 310 nm NB-UVB at an estimated dose of
      100 mJ/cm2 once a day for three days suppressed TDI-induced sneezes and up
      regulation of H1R mRNA in nasal mucosa without induction of apoptosis. These
      findings suggest that repeated intranasal irradiation with low dose of NB-UVB
      could be clinically used as phototherapy of AR.

PMID- 30301598
TI  - Inflammation in human adipose tissues-Shades of gray, rather than white and
      brown.
AB  - Chronic inflammation in adipose tissues has been associated with obesity and
      metabolic syndrome over the years. Various studies using animal models have
      contributed to our knowledge on the pro- and anti- inflammatory mediators that
      regulate obesity. Analyses of cytokine profiles in humans have not revealed a
      clear scenario. Likewise, treatments targeting inflammation to control obesity
      and insulin resistance has not yielded promising results. In this review we
      summarize the data available in human obesity and discuss the possible reasons
      that could explain the difficulties in treating obesity and insulin resistance by
      targeting pro-inflammatory cytokines.

PMID- 30301599
TI  - Cervical cancer cells produce TGF-beta1 through the CD73-adenosine pathway and
      maintain CD73 expression through the autocrine activity of TGF-beta1.
AB  - In cancer, the adenosinergic pathway participates in the generation of an
      immunosuppressive microenvironment and in the promotion of tumor growth through
      the generation of adenosine (Ado). The present study analyzed the participation
      of Ado, generated through the functional activity of the cervical cancer (CeCa)
      pathway in CeCa cells, to induce the expression and secretion of TGF-beta1, as
      well as the participation of this factor to maintain CD73 expression. Ado
      concentrations greater than 10 MUM were necessary to induce an increase of over
      50% in the production and expression of TGF-beta1 in CeCa tumor cells. Blockade
      of A2AR and A2BR with the specific antagonists, ZM241385 and MRS1754,
      respectively, strongly reversed the production of TGF-beta1. TGF-beta1 produced
      by CeCa cells was necessary to maintain CD73 expression because the addition of
      anti-TGF-beta neutralizing antibodies or the inhibition of TGF-betaRI strongly
      reversed the expression of CD73 in the CeCa cells. These results suggested a
      feedback loop in CeCa cells that favors immunosuppressive activity through the
      production of TGF-beta1 and Ado as well as the autocrine activity of TGF-beta1
      and expression of CD73.

PMID- 30301600
TI  - A newly generated neuronal cell model of CLN7 disease reveals aberrant lysosome
      motility and impaired cell survival.
AB  - Mutations in the CLN7/MFSD8 gene encoding the lysosomal membrane protein CLN7 are
      causative of CLN7 disease, an inherited neurodegenerative disorder that typically
      affects children. To gain insight into the pathomechanisms of CLN7 disease, we
      established an immortalized cell line based on cerebellar (Cb) granule neuron
      precursors isolated from Cln7-/- mice. Here, we demonstrate that Cln7-deficient
      neuron-derived Cb cells display an abnormal phenotype that includes increased
      size and defective outward movement of late endosomes and lysosomes as well as
      impaired lysosomal exocytosis. Whereas Cln7-/- Cb cells appeared to be autophagy
      competent, loss of Cln7 resulted in enhanced cell death under prolonged nutrient
      deprivation. Furthermore, reduced cell survival of Cln7-deficient cells was
      accompanied by a significantly impaired protein kinase B/Akt phosphorylation at
      Ser473 during long-term starvation. In summary, our data demonstrate for the
      first time that the putative lysosomal transporter CLN7 is relevant for lysosome
      motility and plays an important role for neuronal cell survival under conditions
      of starvation.

PMID- 30301601
TI  - Fruit and Vegetable Preferences and Practices May Hinder Participation in
      Community-Supported Agriculture Among Low-Income Rural Families.
AB  - OBJECTIVE: Describe fruit and vegetable (FV) preferences and other factors that
      may influence participation in community-supported agriculture (CSA). DESIGN: In
      depth, semi-structured interviews. SETTING: Eight rural/micropolitan communities
      in 4 US states. PARTICIPANTS: There were 41 caregivers and 20 children (8-12years
      of age) from low-income, English-speaking households. PHENOMENA OF INTEREST:
      Knowledge, attitudes, and behaviors regarding FVs; perceived barriers to CSA
      participation. ANALYSIS: Transcribed verbatim and iteratively coded. RESULTS:
      Caregivers and children believed FVs were important to health, yet FVs were not
      featured in dinners or snacks and consumption was challenged by limited
      preferences and neophobia. Few caregivers and children knew about the seasonality
      of FV. Most caregivers were unfamiliar with CSA and had concerns about CSA cost,
      accessibility, produce quality, and selection. CONCLUSIONS AND IMPLICATIONS:
      These qualitative data support improvements in: 1) CSA distribution practices to
      offer flexible payment and pick-up options, more fruits, and self-selection of
      FV; 2) public awareness of produce seasonality and the CSA distribution model as
      necessary precursors to participation, and lower cost for low-income families who
      highlighted this barrier; and 3) capacity to prepare FV by enhancing skills and
      providing time-saving kitchen tools. Approaches to aligning CSA practices with
      the needs and preferences of low-income families warrant further research.

PMID- 30301602
TI  - Preoperative anemia and extensive transfusion during stay-in-hospital are
      critical for patient's mortality: A retrospective multicenter cohort study of
      oncological patients undergoing radical cystectomy.
AB  - BACKGROUND: Preoperative anemia and allogeneic blood transfusions (ABTs) may
      affect outcomes in cancer surgery. The prevalence of anemia, the use of ABTs, the
      risks of transfusions, lengths of stay and mortality of oncological patients
      undergoing radical cystectomy were investigated in three University Hospitals in
      Germany. PATIENTS AND METHODS: Hospital records of 220 consecutive patients
      undergoing radical cystectomy from 2010 to 2012 were retrospectively analyzed for
      independent risk factors of ABT and unfavorable outcomes (readmission, increased
      length of stay (LOS) or death) using multivariate regression analysis. RESULTS:
      Preoperative anemia was present in 40%. 70% of patients received blood
      transfusions. Low preoperative and intraoperative nadir hemoglobin levels were
      associated with receipt of ABT (OR 1.33, P = 0.04 and OR 2.94, P < 0.001
      respectively). Transfusion of ten or more red blood cell units (RBCs) during the
      entire hospital stay was a predictor of an increased LOS (P < 0.001) and death
      (OR 52, 95%CI [5.9, 461.3], P < 0.001), compared to non-transfused patients.
      Preoperative ABT and ASA scores were associated with >=10RBCs. CONCLUSION: Anemic
      patients undergoing radical cystectomy had a high risk to receive ABTs.
      Preoperative transfusions and transfusion of >=10RBCs during the entire hospital
      stay may increase patient's mortality. Prospective, randomized controlled studies
      have to follow this study.

PMID- 30301604
TI  - Focus on pancreatic cancer.

PMID- 30301603
TI  - Sec23a mediates miR-200c augmented oligometastatic to polymetastatic progression.
AB  - BACKGROUND: Cancer treatment is based on tumor staging. Curative intent is only
      applied to localized tumors. Recent studies show that oligometastatic patients
      who have limited number of metastases may benefit from metastasis-directed local
      treatments to achieve long-term survival. However, mechanisms underlying
      oligometastatic to polymetastatic progression remains elusive. METHODS: The
      effects of miR-200c and Sec23a on tumor metastasis were verified both in vitro
      and in vivo. The secretome changes were detected by mass spectrometry. FINDINGS:
      We established a pair of homologous lung-metastasis derived oligometastatic and
      polymetastatic cell lines from human melanoma cancer cell line M14. Using the two
      cell lines, we have identified Sec23a, a gene target of miR-200c, suppresses miR
      200c augmented oligometastatic to polymetastatic progression via its secretome.
      Firstly, miR-200c over-expression and Sec23a interference accelerated
      oligometastatic to polymetatic progression. Secondly, Sec23a functions downstream
      of miR-200c. Thirdly, mass spectrometric analysis of the secretory protein
      profile suggests that Sec23a-dependent secretome may impact metastatic
      colonization by modifying tumor microenvironment. Fourthly, the survival analysis
      using The Cancer Genome Atlas database shows Sec23a as a favorable prognostic
      marker for skin cutaneous melanoma, supporting the clinical relevance of our
      findings. INTERPRETATION: The finding that Sec23a is a suppressor of
      oligometastatic to polymetastatic progression has clinical implications. First,
      it provides a new theoretical framework for the development of treatments that
      prevent oligometastasis to polymetastasis. Second, Sec23a may be used as a
      favorable prognostic marker for the selection of patients with stable
      oligometastatic disease for oligometastasis-based local therapies of curative
      intent. FUND: National Natural Science Foundations of China.

PMID- 30301605
TI  - Functional constipation in children: Is there a place for surgical treatment.

PMID- 30301606
TI  - Ultrasound guidance improves safety and efficiency of central line placements.
AB  - BACKGROUND: Use of ultrasound-guidance for central venous access in adults is the
      standard of care. There is, however, less clarity in the role of routine
      ultrasound use in obtaining venous access in children. We sought to evaluate
      safety and efficiency of the placement of central lines utilizing an ultrasound
      guided approach compared to the traditional, landmark approach in pediatric
      patients. STUDY DESIGN: A single-institution retrospective chart review, using
      CPT codes, was performed for all tunneled central venous catheters in children
      between 2005 and 2017 by the same pediatric surgery group. During the study
      period, a practice change occurred from exclusively landmark-based line placement
      to ultrasound-guided line placement. Groups were divided into three phases: a
      traditional/landmark era (Phase 1), transitional period (Phase 2), and the
      ultrasound era (Phase 3). The primary outcomes analyzed were postoperative chest
      tube insertions and operative time. RESULTS: A total of 2010 tunneled central
      lines were included for analysis: Phase 1 (N = 930), Phase 2 (N = 313) and Phase
      3 (N = 767). Venous access for chemotherapy was the most common indication (29%).
      Phase 1 had a chest tube placement rate of 9.7/1000 procedures, while Phase 2 had
      a rate of 6.4/1000 procedures, and Phase 3 had no chest tube insertions (p =
      0.009). Phase 1 had longer OR times compared to Phase 2 (57 vs. 49, p = 0.0026)
      and Phase 3 (57 vs. 46 min, p < 0.001). CONCLUSIONS: This study represents the
      largest analysis of ultrasound-guided access for children. A complete practice
      transition to the ultrasound-guided approach was feasible within a two-year
      period. The ultrasound-guided approach had a shorter operative time and less
      chest tube insertions than the traditional, landmark technique in children. Level
      III evidence.

PMID- 30301607
TI  - Reimaging in pediatric blunt spleen and liver injury.
AB  - BACKGROUND: APSA guidelines do not recommend routine reimaging for pediatric
      blunt liver or spleen injury (BLSI). This study characterizes the symptoms,
      reimaging, and outcomes associated with a selective reimaging strategy for
      pediatric BLSI patients. METHODS: A planned secondary analysis of reimaging in a
      3-year multi-site prospective study of BLSI patients was completed. Inclusion
      required successful nonoperative management of CT confirmed BLSI without pancreas
      or kidney injury and follow up at 14 or 60 days. Patients with re-injury after
      discharge were excluded. RESULTS: Of 1007 patients with BLSI, 534 (55%) met
      inclusion criteria (median age: 10.18 [IQR: 6, 14]; 62% male). Abdominal
      reimaging was performed on 27/534 (6%) patients; 3 of 27 studies prompting
      hospitalization and/or intervention. Abdominal pain was associated with
      reimaging, but decreased appetite predicted imaging findings associated with
      readmission and intervention. CONCLUSION: Selective abdominal reimaging for BLSI
      was done in 6% of patients, and 11% of studies identified radiologic findings
      associated with intervention or re-hospitalization. A selective reimaging
      strategy appears safe, and even reimaging symptomatic patients rarely results in
      intervention. Reimaging after 14 days did not prompt intervention in any of the
      534 patients managed nonoperatively. LEVEL OF EVIDENCE: Level II, Prognosis.

PMID- 30301608
TI  - Prevalence and natural history of scoliosis and associated congenital vertebral
      anomalies in patients operated for esophageal atresia with or without
      tracheoesophageal fistula.
AB  - BACKGROUND: Scoliosis has been reported after repair of esophageal atresia with
      or without tracheoesophageal fistula (EA-TEF). This study aims to investigate the
      prevalence and natural history of scoliosis and associated congenital vertebral
      anomalies in patients operated for EATEF. METHODS: A retrospective review of
      patients operated for EA-TEF with radiological examination for the presence of
      scoliosis or associated spine congenital anomalies was done on 106 patients (ages
      5-19 years). RESULTS: Scoliosis was found in 53 patients (49%) for which 46 of
      these were in the thoracic region and 33 were right-thoracic curves. After a
      follow-up ranging from 5 to 14 years, four patients (3.7%) out of 106 were
      operated for scoliosis. Right-sided thoracotomy (RST) was the identifiable risk
      factor for scoliosis development; all patients with scoliosis had their EA
      repaired through RST. Congenital vertebral anomalies were found in 8 of those
      patients (7.5%). After a median follow-up of 6.5 years, no patients progressed
      enough to require operation. CONCLUSION: Scoliosis affects one of every two
      patients operated for EA; it may progress to the indication of surgery. RST was
      the identifiable risk factor for scoliosis development.

PMID- 30301609
TI  - Tissue expansion in pediatric patients: a 10-year review.
AB  - BACKGROUND/PURPOSE: Tissue expansion complication rates up to 40% have been
      reported in the pediatric population. This study aims to review one Canadian
      pediatric plastic surgeon's experience with tissue expansion by examining tissue
      expander and flap complication rates, and discussing important aspects of the
      tissue expansion experience. METHODS: This is a retrospective chart review of the
      medical records of all tissue expansion patients treated by the senior author
      during a ten-year period. Data were collected on patient demographics, tissue
      expansion details, complications, and outcomes, and were analyzed descriptively.
      The relationship between tissue expander complications and flap complications was
      analyzed with odds ratio. RESULTS: Ninety-three expanders were placed in 24
      patients during 49 sessions. Complications occurred in 19 expanders (10 patients;
      16 sessions), resulting in premature removal of nine. Only one session was
      unsuccessful; the expander became exposed and was removed after 1 month. The odds
      of having a flap complication were three times greater with preceding tissue
      expander complication (not statistically significant). CONCLUSIONS: Our study
      identifies a 20% expander complication rate in the pediatric population. Patients
      with tissue expander complications subsequently experienced more flap
      complications than those without tissue expander complications. Complications do
      not preclude successful reconstruction. TYPE OF STUDY: Prognostic. LEVEL OF
      EVIDENCE: II.

PMID- 30301610
TI  - Plasmacytoma-like post-kidney-transplant lymphoproliferative disorder confined to
      renal allograft and urinary tract: A case report.
AB  - Post-transplantation lymphoproliferative disorder (PTLD) is a well-know
      complication after organ transplantation. We report a case of a patient who
      developed an extramedullary plasmacytoma-like PTLD around his transplanted kidney
      treated with standard multiple myeloma chemotherapy. Three years after benefiting
      of a deceased donor kidney transplant for an end stage kidney disease secondary
      to nephroangiosclerosis, our patient developed an extra-medullary plasmacytoma
      confined to the transplant compartment. The transplant function was unaltered,
      and due to the absence of reduction of the lesion after immunosuppression
      reduction, a chemotherapy by bortezomib-cyclophosphamide-dexamethasone (VCD)
      known to be efficient in multiple myeloma was initiated. After 6 cycles, positron
      emission tomography (PET) scan showed complete metabolic remission confirming the
      biological exams. This case report suggests that a chemotherapy such as VCD can
      efficiently treat plasmacytoma-like PTLD allowing graft survival. Therefore,
      transplant removal may not be mandatory as the best second line treatment after
      unsuccessfulness reduction of immunosuppression.

PMID- 30301611
TI  - [Non-iodinated contrast media nephrotoxicity].
AB  - The development of interventional radiology techniques regularly exposes patients
      to the potential renal toxocity of iodinated contrast media. Faced with this risk
      of nephrotoxicity, gadolinium-based contrast agents have long been considered as
      a safe alternative to iodinated contrast media, especially in sensitive or at
      risk patients. However, these gadolinium-based contrast agents are not devoid of
      nephrotoxicity and present another risk, a complication related to renal failure,
      the nephrogenic systemic fibrosis. European and US recommendations from health
      agencies have recently come closer, defining groups of patients at risk of
      nephrogenic systemic fibrosis according to their level of renal function and the
      type of gadolinium-based contrast agent used. What are the real renal risks for
      these products? How to evaluate the benefit-risk balance of the patient to choose
      a radiological examination in an informative, effective and safe way? This
      article focuses on the description of the risks of gadolinium-based contrast
      agents, reviews existing recommendations and best practices to guide the choice
      of clinicians.

PMID- 30301612
TI  - Reactive oxygen species mediated placental oxidative stress, mitochondrial
      content, and cell cycle progression through mitogen-activated protein kinases in
      intrauterine growth restricted pigs.
AB  - Intrauterine growth restriction (IUGR) remains a significant obstacle in pig
      production; however, information regarding the relationship between reactive
      oxygen species (ROS)-induced placental dysfunction and IUGR is still unknown.
      This study aimed to explore the placental redox status, mitochondrial content,
      cellular progression, and mitogen-activated protein kinase (MAPK) pathways in
      IUGR. Placental tissues were collected from normal intrauterine gestation (NIUG)
      and IUGR fetuses at delivery. Compared with the NIUG, placental ROS production,
      lipid peroxidation, and DNA damage were increased in IUGR. Placental
      mitochondrial DNA (mtDNA) content and mtDNA-encoded gene expression decreased in
      IUGR. Moreover, p21 phosphorylation increased, cyclin E expression decreased in
      IUGR cases, which showed senescence characteristics. Analysis of signaling
      pathways showed that the ERK1/2 phosphorylation increased whereas the p38 and JNK
      phosphorylation decreased in IUGR. In cultured porcine trophectoderm (pTr) cells,
      exogenous H2O2 increased intracellular ROS production, decreased cell viability
      in a dose-dependent manner. Cell cycle distribution was found to arrest in S and
      G2/M phases. Our findings suggested that IUGR was associated with greater
      placental ROS and oxidative injury, which might be a factor that resulted in
      lower mitochondrial content, microvilli loss and senescence, and activation of
      MAPK pathways.

PMID- 30301613
TI  - [Ultrasound-guided selective nerve blocks for trigger finger surgeries to
      maintain flexion/extension of fingers - Case series].
AB  - BACKGROUND: A patient's ability to move his/her fingers during hand surgery may
      be helpful to surgeons because it allows the effectiveness of the intervention
      evaluation and prediction of hand function in the postoperative period. The
      purpose of this case series is to demonstrate the efficacy of an ultrasound
      guided peripheral nerve block technique to maintain the hand flexor and extensor
      muscles motor function and discuss the benefits of the technique for trigger
      finger surgery. CASE REPORT: Ten patients scheduled to undergo trigger finger
      surgery were selected. The goal was to maintain flexion and extension of the
      fingers during the procedure. Thus, ultrasound-guided ulnar, radial, and medial
      nerve block was performed in the distal third of the forearm, at 5-7cm proximal
      to the wrist. The block was performed with 5mL of 0.375% bupivacaine on each
      nerve. All procedures were uneventfully performed maintaining the flexion and
      extension of the fingers. In two cases, it was observed that the motricity
      maintenance and the patients' ability to move their fingers when requested
      allowed the success of the surgical procedure after the third intraoperative
      evaluation. CONCLUSION: This case series shows that it is possible to maintain
      the motor function of the hand flexor and extensor muscles to perform finger
      trigger surgeries using specific ultrasound-guided distal blocks.

PMID- 30301614
TI  - [Supraclavicular nerve and superior trunk block for surgical treatment of
      clavicle fracture in a patient with Steinert's disease - Case report].
AB  - BACKGROUND AND OBJECTIVES: Ultrasound-guided upper limb blocks may provide great
      benefits to patients with serious diseases. Patients with Steinert's disease have
      muscle weakness and risk of triggering myotony or malignant hyperthermia due to
      the use of anesthetic agents and surgical stress. The objective of this report
      was to demonstrate a viable alternative for clavicle fracture surgery with upper
      trunk and supraclavicular nerve block, thus reducing the spread of local
      anesthetic to the phrenic nerve in a patient with muscular dystrophy. CASE
      REPORT: A 53-year-old male patient with Steinert's disease, associated with
      dyspnea, hoarseness and dysphagia, referred to the surgical theater for
      osteosynthesis of clavicle fracture. Upper limb (1mL 0.75% ropivacaine) and
      supraclavicular nerve block (1mL 0.75% ropivacaine in each branch) were combined
      with venous anesthesia with propofol under laryngeal mask (infusion pump target
      of 4 mcg.Ml-1). Upon awakening, the patient had no pain or respiratory
      complaints. He was transferred to the ICU for immediate postoperative follow-up
      with discharge from this unit after 24hours without complications. CONCLUSIONS:
      The superior trunk and cervical plexus block associated with venous anesthesia
      under laryngeal mask, without the use of opioids, proved to be adequate in the
      case of a patient with clavicle fracture and Steinert's disease. With the use of
      ultrasonography in regional anesthesia it is possible to perform increasingly
      selective blocks, thus allowing greater security for the anesthetic-surgical
      procedure and lower morbidity for the patient.

PMID- 30301615
TI  - Dysglycaemia in CF - Why are investigating it, what should we measure and how
      should we treat it?

PMID- 30301616
TI  - Patent ductus arteriosus: The rare cause of left bronchial obstruction in neonate
      with pulmonary atresia.

PMID- 30301617
TI  - Impact of Chronic Total Coronary Occlusion Location on Long-term Survival After
      Percutaneous Coronary Intervention.
AB  - INTRODUCTION AND OBJECTIVES: Limited data are available on the clinical outcomes
      of optimal medical therapy (OMT) compared with revascularization by percutaneous
      coronary intervention (PCI) in patients with chronic total coronary occlusion
      (CTO) of the proximal or middle left anterior descending artery (pmLAD).
      Therefore, the objective of this study was to compare the long-term outcomes of
      patients with pmLAD CTO who were treated with a PCI strategy with those of
      patients treated with an OMT strategy. METHODS: Between March 2003 and February
      2012, 2024 patients with CTO were enrolled in a single-center registry. Among
      this patient group, we excluded CTO patients who underwent coronary artery bypass
      grafting. After the exclusion, a total of 1547 patients remained. They were
      stratified according to classification of coronary segments (pmLAD or non-pmLAD
      CTO) and the initial treatment strategy (OMT or PCI). Propensity score matching
      was performed. The primary outcome was cardiac death. RESULTS: The median follow
      up was 45.9 (interquartile range, 22.9-71.1) months. After propensity score
      matching, the incidence of cardiac death (HR, 0.54; 95%C, 0.31-0.94, P=.029) was
      significantly lower in the PCI with pmLAD CTO group than in the OMT group. In
      contrast, no significant difference was found in the rate of cardiac death
      between the PCI and OMT groups with non-pmLAD CTO (HR, 0.62; 95%CI, 0.27-1.42,
      P=.26). CONCLUSIONS: As an initial treatment strategy, PCI of pmLAD CTO, but not
      PCI of non-pmLAD, is associated with improved long-term survival.

PMID- 30301618
TI  - [Mini-sling versus transobturator sling: Efficiency and morbidity].
AB  - OBJECTIVE: To compare the effectiveness of an ALTIS(r) mini-sling and a
      conventionnal suburethral sling TVT-ABBREVO(r) for treatment of female stress
      urinary incontinence. METHODS: A single-center retrospective study included all
      female patients fitted with a conventional transobturator tape (TVT-ABBREVO(r))
      or mini-sling (ALTIS(r)), during 2015, in Angers university hospital. The success
      rate was defined by no urine leakage during a cough test on clinical examination,
      improved quality of life defined by a PGI-I (Patient Global Impression of
      Improvement) score of 1 to 3, and no stress urinary incontinence on USP (Urinary
      Symptom Profile) questionnaire. Morbidity associated with slings and
      perioperative data were also recorded. RESULTS: Ninety-two patients were included
      (39 in the ALTIS group and 53 in the ABBREVO group). The average follow-up was
      13.55 months. The success rate was not significantly different in ALTIS group for
      the negative cough test (89.7% vs 94.3% in ABBREVO group, P=0.45), for the
      absence of urinary leakage reported on the USP questionnaire (87.2% vs 90.6% in
      ABBREVO group, P=0.61), or for the improvement of the quality of life with a PGI
      I score between 1 and 3 (82.1% vs 86.8% in ABBREVO group, P=0.53). On the other
      hand, more patients were fully satisfied, with a PGI-I quality of life score of
      1, in ABBREVO group than in ALTIS group (67.9% compared with 46.2%, P=0.03).
      Immediate postoperative pain was significantly less intense in ALTIS group than
      in ABBREVO group (average VAS score of 0.5 comparated with 1.3, P=0.01), but this
      difference had disappeared one week after surgery. The rates of other
      complications were similar in both groups. CONCLUSION: The functional results of
      the ALTIS and TVT-ABBREVO(r) slings appear similar in the treatment of female
      stress urinary incontinence.

PMID- 30301619
TI  - Evaluation of candidate reference genes for investigation of the uterine tissue
      and corpus luteum of pigs on day 6 after artificial insemination.
AB  - Housekeeping genes (HKG) are genes necessary for the maintenance of basal
      cellular functions, regardless of the specific roles within a tissue. It,
      therefore, is expected that these genes will maintain a relatively constant
      expression profile when there are varying physiological conditions. The
      identification of tissue specific reference genes is highly important for the
      normalization of gene expression profiles among different tissues. In this sow
      study, the objective was to identify stable reference genes in the uterine tissue
      and corpus luteum (CL), 6 days post-artificial insemination. The stability of
      ubiquitin (UBB), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), DNA
      topoisomerase 2-beta (TOP2B), histone H3 (H3F3A) and hypoxanthine-guanine
      phosphoribosyltransferase 1 (HPRT1) abundances of mRNA were evaluated using the
      Bestkeeper technique. Briefly, total RNA was extracted for each tissue from 20
      gilts (n = 20), processed by RT-qPCR and submitted to analysis using the
      Bestkeeper technique, which allowed for the evaluation of the consistency in
      abundance of mRNA for the reference genes. For all evaluated genes, the abundance
      of mRNA was relatively consistent in the uterine tissue, with the greatest
      abundance being for the GAPDH and TOP2B genes. The analysis of these genes in the
      CL, however, indicated there was a relatively greater variation of mRNA abundance
      for the various reference genes. Data suggest that UBB was the reference gene
      with the most consistent relative abundance of mRNA and that this gene could be
      used as a reference for corpora lutea analyses of mRNA.

PMID- 30301620
TI  - Effect of length of time post-mortem on quality and freezing capacity of
      Cantabric chamois (Rupicapra pyrenaica parva) epididymal spermatozoa.
AB  - Genome Resource Banks are keystones in the ex-situ conservation of wild species.
      Post-mortem (PM) collection of epididymal spermatozoa is an opportunistic and
      valuable source of germplasm, the time from the death of the animal limits its
      use. Seeking to improve germplasm preservation strategies for the chamois
      (Rupicapra sp.), the effect of PM time on epididymal sperm quality and
      freezability was studied using the Cantabrian chamois. Samples were classified
      according to PM collection time, up to 216 h (refrigerated), and cryopreserved
      (Tris-citric acid-fructose, 430 mOsm/kg, 15% egg yolk, 8% glycerol; freezing at 
      20  degrees C/min). Sperm quality was assessed after recovery and post-thawing
      (motility by CASA, HOS test, abnormal forms, cytoplasmic droplets, and viability
      and acrosomal damage by flow cytometry). The sperm mass pH and osmolality showed
      a positive correlation with time. Total sperm motility dropped after 2 days PM,
      with progressivity and sperm velocities remained similar up to 3 days PM. Sperm
      freezability was acceptable, with the post-thawing HOST, motility, progressivity,
      VAP, VCL, VSL and BCF negatively correlating with PM time. Overall, chamois
      epidydimal samples were not adequate for preservation after 6 days PM.
      Freezability capacity could make these spermatozoa suitable for specific ART even
      if kept refrigerated for several days PM.

PMID- 30301621
TI  - Sperm quality in wild-caught and farmed males of the European eel (Anguilla
      anguilla).
AB  - Sperm density and performance of wild and farmed male European eels were
      evaluated to investigate the effect of maintenance in captivity on ejaculate
      quality. Hormonal stimulation (with human chorionic gonadotropin) lasted for 17
      weeks. Different origins of the male European eels partially influenced the
      quality of the ejaculates. Indeed, wild animals (i.e., collected at a natural
      site) had greater sperm longevity during the hormonal stimulation, whereas there
      was no significant effect of the origin on sperm density, spermatocrit, the
      percentage of motile sperm, and plasma testosterone concentrations. The different
      origins of the males also affected fatty acid sperm content, with greater
      unsaturated fatty acid and omega-6 concentrations in wild eels and lesser
      concentrations of saturated fatty acids and omega-3 fatty acids in farmed eels.
      Regarding sperm quality of European eels, this is the first study that takes into
      account the effect of different origins of stimulated males (wild-caught compared
      with farmed) on sperm quality, and these findings may help to improve the
      production of high-quality gametes in this endangered species.

PMID- 30301622
TI  - Effect of reduced glutathione (GSH) supplementation to Tris-egg yolk extender on
      chilled semen variables of dogs.
AB  - One reason for reduced longevity of chilled dog semen is oxidative stress. The
      antioxidant glutathione (GSH) improves viability of frozen-thawed dog sperm, but
      its effect on chilled dog semen has not been investigated. An experiment
      consisting of two parts was performed: Sperm rich fractions, SRF, were split,
      diluted with a Tris-egg yolk (TEY) extender containing 0, 5 or 10 mM GSH and
      stored at 4  degrees C for 10 days (Part 1; n = 19) or 4 days (Part 2; n = 11),
      respectively. For Part 1 of the study, percentage (%) of motile, viable,
      morphologically abnormal spermatozoa and % acrosomal deviations were assessed on
      days 0, 1, 2, 4 and 10 after dilution. For % sperm motility, samples from all
      three aliquots of each SRF (0/5/10 mM GSH) were pipetted simultaneously and
      analysed in a randomised order (time point of analysis, TPA). In Part 2 of the
      study, motility analysis was performed during 4 days storage and samples were
      analysed immediately after pipetting (part 2). Most investigated parameters were
      affected by storage time. For motility variables, there was an effect of GSH
      identified for circular, CM (ANOVA, Part 1: P =  0.05, Part 2: P < 0.0001) and
      local motility, LM (ANOVA, Part 2: P =  0.004). Furthermore, there was a trend
      for an interaction between time and sperm treatment for CM (Part 2: P =  0.077).
      In conclusion, in the present study there was not an overall positive effect of
      GSH addition (5/10 mM) on sperm motility in chilled dog semen samples that were
      characterised to be of good quality during 4- and 10-days of storage.

PMID- 30301623
TI  - Towards quantitative analysis of enamel erosion by focused ion beam tomography.
AB  - OBJECTIVES: The purpose of this work is a proof of concept to introduce a new
      quantitative 3D-analysis of dental erosion obtained by focused ion beam (FIB)
      tomography associated with silver nitrate penetration into porosities in etched
      enamel. METHODS: One sample selected was sound enamel after removal of the
      aprismatic surface. The other was studied after applying an additional attack
      with orthophosphoric acid. Both surfaces were infiltrated with silver nitrate via
      immersion. After dehydration, samples were observed in a dual column FIB/SEM
      station. Serial FIB sectioning was conducted with a current of 3nA at 30keV and
      an increment step of 20nm for the healthy enamel and of 40nm for the etched one.
      3D analysis was performed with Fiji software and BoneJ plugin and several
      parameters were obtained to characterize the tissue: non-mineralized phase
      content (NMP), connected porosity fraction (CPF) and degree of anisotropy (DA) of
      the NMP. RESULTS: Healthy enamel showed an NMP content of 0.5vol.%, with a
      bimodal distribution of non-mineralized regions, inside the prisms and between
      the prisms. No silver penetration was noticed in the healthy enamel,
      demonstrating the absence of open porosity. In contrast, silver nitrate
      penetration after acidic exposure was observed, up to a depth of 12MUm, which
      allowed the calculation of an interconnected porosity volume fraction (CPF) of
      3.1vol.%, mostly between the prisms. Values for DA of 0.56 for sound enamel and
      0.81 for acid-etched surface were determined, highlighting a higher degree of
      anisotropy in the latter. SIGNIFICANCE: Quantitative analysis of FIB tomography
      using NMP, CPF and DA should contribute to a better understanding and follow up
      of dental erosion, correlation between erosion and attrition or abrasion process,
      and the ability to develop enamel remineralization procedures.

PMID- 30301624
TI  - Biostable, antidegradative and antimicrobial restorative systems based on host
      biomaterials and microbial interactions.
AB  - OBJECTIVES: Despite decades of development and their status as the restorative
      material of choice for dentists, resin composite restoratives and adhesives
      exhibit a number of shortcomings that limit their long-term survival in the oral
      cavity. Herein we review past and current work to understand these challenges and
      approaches to improve dental materials and extend restoration service life.
      METHODS: Peer-reviewed work from a number of researchers as well as our own are
      summarized and analyzed. We also include yet-unpublished work of our own.
      Challenges to dental materials, methods to assess new materials, and recent
      material improvements and research directions are presented. RESULTS: Mechanical
      stress, host- and bacterial-biodegradation, and secondary caries formation all
      contribute to restoration failure. In particular, several host- and bacterial
      derived enzymes degrade the resin and collagen components of the hybrid layer,
      expanding the marginal gap and increasing access to bacteria and saliva.
      Furthermore, the virulence of cariogenic bacteria is up-regulated by resin
      biodegradation by-products, creating a positive feedback loop that increases
      biodegradation. These factors work synergistically to degrade the restoration
      margin, leading to secondary caries and restoration failure. Significant progress
      has been made to produce hydrolytically stable resins to resist biodegradation,
      as well as antimicrobial materials to reduce bacterial load around the
      restoration. Ideally, these two approaches should be combined in a holistic
      approach to restoration preservation. SIGNIFICANCE: The oral cavity is a complex
      environment that poses an array of challenges to long-term material success;
      materials testing conditions should be comprehensive and closely mimic pathogenic
      oral conditions.

PMID- 30301625
TI  - Reply to: "Finding fibroblast growth factor 19 during cholestasis: Does x mark
      the spot?

PMID- 30301626
TI  - Hip Arthroscopy in Patients Ages 50 Years or Older: Minimum 5-Year Outcomes,
      Survivorship, and Risk Factors for Conversion to Total Hip Replacement.
AB  - PURPOSE: To report minimum 5-year outcomes and risk factors for conversion to
      total hip arthroplasty (THA) in patients >=50 years old undergoing hip
      arthroscopy to treat labral tears and femoroacetabular impingement (FAI).
      METHODS: Data were prospectively collected on patients who underwent hip
      arthroscopy to treat labral tears and FAI between February 2008 and January 2012.
      The inclusion criteria were >=50 years old at surgery, arthroscopic treatment for
      both labral tears and FAI, and preoperative patient-reported outcome (PRO) scores
      for modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), Hip Outcome
      Score-Sports Specific Subscale (HOS-SSS), and Visual Analog Scale (VAS). The
      exclusion criteria were Tonnis grade > 1 and previous hip conditions or
      surgeries. RESULTS: Of 103 eligible cases, 94 hips (91.3%) had minimum 5-year
      follow-up at a mean of 70.1 months (range, 60.0-95.1 months). All PROs and VASs
      demonstrated significant improvement at latest follow-up (P = .0001). Mean
      patient satisfaction was 8.4. All mean scores demonstrated durability from 2
      years to latest follow-up, and NAHS (P = .009), HOS-SSS (P = .02), and VAS (P =
      .04) continued to significantly improve. Fifty-one (54.3%) of cases reached
      patient acceptable symptomatic state for mHHS, and 49 cases (52.1%) achieved
      minimal clinically important difference for this outcome measure. Four cases
      (4.3%) required secondary arthroscopy, and survivorship was 72.3%. Compared with
      survivors, the subgroup requiring THA demonstrated higher body mass indexes (P =
      .01), had larger alpha angles (P = .0200) and smaller lateral center-edge angles
      (P = .0200), and had higher proportions of Tonnis grade 1 (P = .0012), acetabular
      Outerbridge grade >= 2 (P = .0500), and femoral head Outerbridge grade >=2 (P =
      .0001). CONCLUSIONS: Hip arthroscopy for the treatment of labral tears and FAI in
      patients >=50 years old demonstrates statistically significant PRO improvements
      at minimum 5-year follow-up. However, due to potential for subsequent need for
      THA in a subset of this population, surgeons should use rigorous selection
      criteria and counsel patients appropriately. LEVEL OF EVIDENCE: Level IV, case
      series.

PMID- 30301627
TI  - Preoperative and Intraoperative Predictors of Long-Term Acceptable Knee Function
      and Osteoarthritis After Anterior Cruciate Ligament Reconstruction: An Analysis
      Based on 2 Randomized Controlled Trials.
AB  - PURPOSE: To determine preoperative predictors of long-term acceptable knee
      function and the development of osteoarthritis (OA) in long-term follow-up after
      anterior cruciate ligament (ACL) reconstruction. METHODS: This study is a long
      term follow-up of 2 previous randomized controlled trials that included 193
      patients who underwent unilateral ACL reconstruction with ipsilateral hamstring
      tendon or patellar tendon autografts. Patients who suffered multiligament
      injuries, major meniscal injuries, chondral lesions requiring surgical treatment,
      or had a previous ACL reconstruction were excluded. Patient demographics,
      preoperative clinical assessments, and intraoperative findings were used to
      create stepwise multivariable regression models to determine the patient
      acceptable symptom state (PASS) in the International Knee Documentation Committee
      and the development of OA defined as a Kellgren-Lawrence grade >=2. Knee laxity
      measurements, hop performance, patient-reported outcome, and concomitant injuries
      were determined as variables. RESULTS: A total of 147 patients (63.7% men) were
      eligible for inclusion, with a mean follow-up of 16.4 +/- 1.3 years. The patients
      were an average age of 27.9 +/- 8.3 years at the time of ACL reconstruction. One
      half of the cohort reported an International Knee Documentation Committee
      evaluation system score above the PASS cutoff. The presence of a concomitant
      injury at operation (odds ratio [OR], 2.61; 95% confidence interval [CI], 1.10
      6.21; P = .030) and greater preoperative anteroposterior laxity (OR, 1.87; 95%
      CI, 1.05-3.35; P = .034) increased the likelihood of achieving a PASS. A longer
      period between ACL injury and reconstruction (OR, 2.25; 95% CI, 1.02-5.00; P =
      .046) and older age at reconstruction (OR, 2.28; 95% CI, 1.34-3.86; P = .0023)
      increased the odds of developing OA at follow-up. CONCLUSIONS: Patients who were
      older at the time of ACL reconstruction and had waited >1 year between the injury
      and reconstruction ran an increased risk of having OA 16 years after
      reconstruction. One in 2 patients reported acceptable long-term knee function,
      but no risk factor for poorer subjective knee function was identified. Patients
      who had a minor concomitant injury and increased preoperative anteroposterior
      knee laxity had increased odds of reporting an acceptable long-term knee
      function. LEVEL OF EVIDENCE: Level II; prospective comparative study.

PMID- 30301628
TI  - Which Technique Is Better for Treating Patellar Dislocation? A Systematic Review
      and Meta-analysis.
AB  - PURPOSE: To clarify the discrepancy in surgical options and present evidence to
      treat patellar dislocation by evaluating which of the techniques yields better
      improvement in stability and functional recovery for patellar dislocation.
      METHODS: The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web
      of Science, and Scopus electronic databases were searched for relevant articles
      comparing the outcomes of medial patellofemoral ligament (MPFL) treatment
      published up until August 2017. Data searching, extraction, analysis, and quality
      assessment were performed based on The Cochrane Collaboration guidelines.
      Clinical outcomes were evaluated using various outcome values in various
      techniques. For results with high heterogeneity, 95% prediction intervals (PIs)
      were also investigated. RESULTS: Eleven clinical studies were investigated. In
      patients with primary patellar dislocation, there were no significant differences
      in all evaluated outcomes between the conservative and surgical treatment groups.
      For patients with recurrent patellar dislocation, MPFL reconstruction was
      associated with a favorable Kujala score (mean difference, -8.91; 95% confidence
      interval, -14.05 to -3.77; I2 = 94%; 95% PI, -9.64 to -8.1) and Lysholm score
      (mean difference, -13.51; 95% confidence interval, -21.35 to -5.68; I2 = 96%; 95%
      PI, -14.86 to -12.16) when compared with soft tissue realignment surgery.
      CONCLUSIONS: Although surgical treatment of the MPFL for primary patellar
      dislocation is not superior to conservative treatment in restoring knee function
      and clinical outcomes, MPFL reconstruction is associated with more favorable
      clinical outcomes compared with medial soft tissue realignment surgery in
      patients with recurrent patellar dislocation. Double-bundle MPFL reconstruction
      seems to provide more favorable outcomes than single-bundle MPFL reconstruction,
      but this finding should be interpreted with caution because the evidence levels
      were low and were from only a few studies. LEVEL OF EVIDENCE: Level III, meta
      analysis.

PMID- 30301629
TI  - Bacterial Deoxyribonucleic Acid Is Often Present in Failed Revision Anterior
      Cruciate Ligament Reconstructions.
AB  - PURPOSE: To determine whether bacterial DNA will be detectable by polymerase
      chain reaction (PCR) in torn graft tissue at the time of revision anterior
      cruciate ligament reconstruction (ACLR). METHODS: A total of 31 consecutive
      revision ACLR cases from 1 center from 2014-2016 were recruited. No patients had
      clinical signs of infection on presentation. Torn graft tissue was obtained in
      revision cases and subjected to clinical culture and PCR analysis with a
      universal bacterial primer. Fluorescence microscopy was used to confirm the
      presence of a biofilm. We obtained negative control samples of water open to air
      on the field and excess primary ACLR graft tissue, as well as torn native
      ligament, to evaluate for PCR positivity due to environmental contamination.
      RESULTS: Clinical cultures were positive (coagulase-negative Staphylococcus) in 1
      revision case (3%, 1 of 31). Bacterial DNA was detectable in most revision ACLR
      cases (87.0%, 27 of 31), and there was a low rate of PCR positivity in negative
      control samples of water open to air (0%, 0 of 3), excess primary ACLR graft
      tissue after passage (20%, 1 of 5), or native torn ligament (20%, 1 of 5).
      Bacterial biofilm presence on failed graft tissue as well as monofilament suture
      was visually confirmed with fluorescence microscopy. CONCLUSIONS: Bacterial DNA
      is frequently present in failed ACLR grafts, with high rates of DNA detection by
      PCR but low culture positivity. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 30301630
TI  - Type VIII SLAP Repair at Midterm Follow-Up: Throwers Have Greater Pain, Decreased
      Function, and Poorer Return to Play.
AB  - PURPOSE: To evaluate and compare midterm outcomes and return to play (RTP) of
      throwers and nonthrowers who underwent type VIII SLAP repair. METHODS: With 4
      year minimum follow-up, stability, pain, range of motion (ROM), Kerlan-Jobe
      Orthopaedic Clinic (KJOC), and American Shoulder and Elbow Surgeons (ASES)
      scores; surgical satisfaction; and RTP were compared between throwing and
      nonthrowing athletes who underwent repair of type VIII SLAP lesions between 2003
      and 2014. RESULTS: 46 patients (27 throwers and 19 nonthrowers) were included.
      The athletes were aged 24.2 +/- 9.2 years at the time of surgery. The mean follow
      up period was 6.6 +/- 2.0 years. A significant improvement in stability, pain,
      ROM, KJOC, and ASES scores was seen after surgery in both throwers and
      nonthrowers (P < .05). When postoperative outcomes were compared, throwers had
      more pain (P = .047), decreased ROM (P = .03), lower KJOC scores (52.2 +/- 24.0
      in throwers vs 87.5 +/- 18.8 in nonthrowers, P < .0001), and lower ASES scores
      (43.5 +/- 7.1 in throwers vs 48.3 +/- 3.0 nonthrowers, P = .02). There was no
      difference in stability (P = .06), surgical satisfaction (96.3% in throwers vs
      100% in nonthrowers, P > .99), or overall RTP (70.4% in throwers vs 94.7% in
      nonthrowers, P = .06). However, throwers were less likely to RTP at their
      preoperative level (37.0% in throwers vs 73.7% in nonthrowers, P = .02).
      CONCLUSIONS: Surgical repair of type VIII SLAP tears led to significant
      improvements in stability, pain, ROM, and outcome scores at midterm follow-up.
      Compared with nonthrowers, throwers had significantly more pain, less ROM, and
      worse function. Throwers were also less likely to RTP at their preoperative
      level. These findings suggest that type VIII SLAP tears should be repaired in all
      athletes because outcomes do improve, although throwers require specific
      counseling and expectation management regarding their ability to RTP at their
      preinjury level. LEVEL OF EVIDENCE: Level III, therapeutic case-control study.

PMID- 30301631
TI  - Primary Anterolateral Ligament Rupture in Patients Requiring Revision Anterior
      Cruciate Ligament Reconstruction: A Retrospective Case-Control Magnetic Resonance
      Imaging Review.
AB  - PURPOSE: To compare the initial rate of anterolateral ligament (ALL) injury at
      the time of anterior cruciate ligament (ACL) rupture in patients who subsequently
      experienced ACL reconstruction graft failure versus patients who did not
      experience subsequent ACL reconstruction graft failure. METHODS: Our
      institution's electronic medical record database was queried for patients who
      underwent primary ACL reconstruction with subsequent ACL graft rupture. Exclusion
      criteria included unavailable MRI scan, chronic ACL injury, multi-ligamentous
      injury, previous ACL reconstruction, and age younger than 13 or older than 50
      years. Each patient was paired with an age-, gender-, and graft-matched control
      who underwent ACL reconstruction without subsequent graft rupture. Each patient
      was diagnosed with an intact, partially injured, or fully ruptured ALL on initial
      MRI. The location of ALL injury was also noted. The incidence and location of ALL
      rupture were compared using chi2 analysis. RESULTS: 1,967 patients underwent
      primary ACL reconstruction. 128 patients experienced ACL graft rupture, and 55
      patients (43%) had MRI scans available for review. 39 of these patients fulfilled
      inclusion criteria and were matched with a control patient. In the revision
      group, the ALL was diagnosed as intact, partially torn, and completely torn in
      17, 14, and 8 patients, respectively, compared to 18, 13, and 8 patients,
      respectively in the control group. No difference was found in frequency of ALL
      rupture (Pearson chi2 = 0.066; P = .968) or rupture location (Pearson chi2 =
      4.00, P = 0.135). CONCLUSIONS: The incidence of initial ALL injury as documented
      on MRI was not different in patients who experienced subsequent ACL graft rupture
      compared with patients who did not experience ACL graft rupture after primary ACL
      reconstruction. The ALL was more commonly injured on the tibial side in patients
      with ACL graft rupture and femoral-sided lesions were more common in control
      patients. LEVEL OF EVIDENCE: Level III, prognostic case-control study.

PMID- 30301632
TI  - Identification of a Patient Acceptable Symptomatic State Score for the
      International Hip Outcome Tool in People Undergoing Hip Arthroscopy.
AB  - PURPOSE: To determine a Patient Acceptable Symptomatic State (PASS) score for the
      33-item International Hip Outcome Tool (iHOT-33) in people undergoing hip
      arthroscopy for primary diagnoses of femoroacetabular impingement syndrome,
      acetabular labral tears, and/or ligamentum teres pathology. METHODS: Consecutive
      participants underwent hip arthroscopy by a single surgeon between August 2011
      and May 2016. Participants were included if they were between ages 18 and 60
      years and underwent hip arthroscopy for femoroacetabular impingement syndrome,
      acetabular labral tears, or ligamentum teres pathology. Participants were
      excluded if they did not speak sufficient English to complete the iHOT-33, had
      evidence of hip dysplasia, had less than 2 mm of joint space on anteroposterior
      radiograph, or underwent subsequent total hip replacement surgery. Participants
      completed the iHOT-33 preoperatively and at a minimum of 1 to a maximum of 5
      years postoperatively. Participants were also asked to answer yes or no to the
      external anchor question of "Taking into account all the activities you do during
      your daily life, your level of pain and also your functional impairment, are you
      satisfied with your current state following your surgery?" A receiver operating
      characteristic (ROC) curve was used to identify the PASS score. Multiple logistic
      regression was performed to determine if patient factors, primary preoperative
      diagnosis, or intraoperative findings predicted achievement of the PASS score.
      RESULTS: A total of 117 participants undergoing hip arthroscopy were included: 72
      women (61.1%) and 45 men (38.5%) with mean age of 36.81 years (18-59). Forty-two
      (35.9%) had cam morphology, 18 (15.4%) had pincer morphology, 78 (67.2%) had
      labral tears, and 97 (82.9%) had ligamentum teres tears. Mean time to final
      follow-up was 2.25 years (range, 1-5). The PASS score at a mean of 2.25 years
      postoperatively was 58 as determined by the cutoff threshold on the ROC curve
      with the lowest difference between sensitivity and specificity (area under the
      ROC curve 0.88; P < .01; 95% confidence interval [CI], 0.81-0.95). No factors
      were predictors of achievement of the PASS score in this study (P > .05),
      including age (odds ratio [OR], 0.71; 95% CI, 0.32-1.56), sex (OR, 1.02; 95%, CI
      0.98-1.06), preoperative iHOT-33 score (OR, 1.002; 95% CI, 0.98-1.03), primary
      preoperative diagnosis (OR, 0.86; 95% CI, 0.53-1.40), cam morphology (OR, 1.19;
      95% CI, 0.54-2.64), Pincer morphology (OR, 0.50; 95%, CI 0.18-1.38), acetabular
      labral tears (OR, 1.93; 95% CI, 0.88-4.26), Outerbridge grade 3-4 chondral damage
      (OR, 0.97; 95% CI, 0.42-2.25), and ligamentum teres pathology (OR, 0.95; 95% CI,
      0.35-2.61). CONCLUSIONS: This study reports a PASS score of 58 for the iHOT-33 at
      2 years following hip arthroscopy. The PASS score will assist in assessing
      response to hip arthroscopy in research and clinical settings. LEVEL OF EVIDENCE:
      Level II, retrospective prognostic study.

PMID- 30301633
TI  - Loop Length Change of an Adjustable-Length Femoral Cortical Suspension Device in
      Anatomic Rectangular Tunnel Anterior Cruciate Ligament Reconstruction With a Bone
      Patellar Tendon-Bone Graft and Associated Clinical Outcomes.
AB  - PURPOSE: To evaluate loop length changes of an adjustable femoral cortical
      suspensory fixation device and assess the clinical results after anatomic
      rectangular tunnel anterior cruciate ligament (ART-ACL) reconstruction with a
      bone-tendon-bone (BTB) graft. METHODS: The study included 50 patients who
      underwent ART-ACL reconstruction with a BTB graft fixed using the adjustable
      length device BTB TightRope for femoral fixation between July 2013 and December
      2014. Computed tomography examinations were performed at 1 and 12 weeks after the
      surgery. Loop length was measured in the reconstructed plane just parallel to the
      femoral tunnel, including the bone plug and the button. Measurement was performed
      thrice, and the mean value was used. Loop length change was defined as the
      difference in loop length between 1 and 12 weeks after the surgery. A paired t
      test was conducted with the effect size for statistical analysis. At 2 years
      postoperatively, clinical evaluations, including subjective and objective
      assessments, were performed. RESULTS: The mean loop lengths at 1 and 12 weeks
      were 25.77 +/- 3.88 mm and 25.81 +/- 3.89 mm, respectively, with a significant
      difference (P = .01). However, the effect size was 0.01, suggesting that the
      difference was not meaningful. The mean individual loop length change was 0.04 +/
      0.13 mm. All individual loop length changes were within the measurement error
      range. At 2 years postoperatively, 49 patients (98%) were graded as normal or
      nearly normal according to the International Knee Documentation Committee form.
      The mean side-to-side difference in anterior laxity at manual maximum force was
      0.2 +/- 0.5 mm. CONCLUSIONS: The loop length change of an adjustable-length
      femoral cortical suspension device was negligible after ART-ACL reconstruction
      with a BTB graft. This ART-ACL reconstruction with a BTB graft using an
      adjustable-length device could safely provide sufficient stability to the
      operated knee. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 30301634
TI  - Return to Golf After Arthroscopic Management of Femoroacetabular Impingement
      Syndrome.
AB  - PURPOSE: To investigate if patients who reported playing golf before arthroscopic
      hip surgery for femoroacetabular impingement syndrome were able to return to
      playing golf postoperatively. METHODS: The study was a retrospective analysis of
      all consecutive patients undergoing hip arthroscopy for femoroacetabular
      impingement syndrome between 2012 and 2014. Inclusion criteria required that a
      patient (1) reported playing golf before the surgery, (2) had a minimum 2-year
      follow-up, and (3) completed patient-reported outcome measures. An electronic
      postoperative return to golf questionnaire was completed by patients who reported
      golf as an activity. To evaluate patients' ability to return to golf after
      surgery, the following variables were analyzed with paired samples t test and chi
      square tests: handedness, holes played, modified-Harris Hip Score, and Hip
      Outcome Score Activity of Daily Living and Sports-Specific Subscale. RESULTS: A
      total of 29 patients (22 men; age, 36.0 +/- 11.9 years) with a minimum of 24
      months of follow-up who self-reported playing golf preoperatively were included
      in the analysis. Preoperatively, 23 patients (79%) had discontinued golfing owing
      to activity-related hip complaints. At the final follow-up, all patients had
      significant improvements in the Hip Outcome Score Activity of Daily Living
      (preoperatively, 65.9 +/- 19.9; postoperatively, 91.5 +/- 12.8; P < .0001), the
      Hip Outcome Score Sports-Specific Subscale (38.2 +/- 23.5, 79.7 +/- 28.8; P =
      .0002), and modified-Harris Hip Score (54.8 +/- 15.6; 84.2 +/- 15.8; P < .0001).
      Additionally, there was a decrease in pain from 7.34 +/- 1.63 to 1.71 +/- 2.3
      postoperatively (P < .0001), and 97% of patients returned to golf at an average
      of 7.2 months postoperatively. Postoperatively, 55% of patients (n = 16) noted
      improved golfing performance, 41% (n = 11) returned to their preinjury level, 1
      patient (3%) returned at a lower level owing to non-hip-related problems, and 1
      (3%) did not return to golf owing to fear of reinjury. CONCLUSIONS: Arthroscopic
      treatment of femoroacetabular impingement syndrome in patients who reported
      playing golf before surgery resulted in significant improvements in hip function
      and predictably high rates of patient satisfaction, with 97% returning to golfing
      activity and 55% noting improvement from preinjury sporting performance. LEVEL OF
      EVIDENCE: Level IV, retrospective case series.

PMID- 30301635
TI  - Evaluation of NCAM and c-Kit as hepatic progenitor cell markers for intrahepatic
      cholangiocarcinomas.
AB  - BACKGROUND: Intrahepatic cholangiocarcinomas (ICCs) are primary liver
      malignancies and are the second most common type of malignancy after
      hepatocellular carcinoma. ICCs are heterogeneous in clinical features, genotype,
      and biological behavior, suggesting that ICCs can initiate in different cell
      lineages. AIM: We investigated intrahepatic cholangiocarcinoma RBE cell lines for
      the markers neural cell adhesion molecule (NCAM) and c-Kit, which possess hepatic
      progenitor cells properties. METHODS: NCAM + c-Kit + cells were tested for
      hepatic progenitor cell properties including proliferation ability, colony
      formation, spheroid formation, and invasiveness in NOD/SCID mice. The Agilent
      Whole Human Genome Microarray Kit was used to evaluate differences in gene
      expression related to stem cell signaling pathways between NCAM + c-Kit + and
      NCAM-c-Kit- subset cells. Microarray results were further confirmed by real-time
      RT-PCR. RESULTS: NCAM + c-Kit + cells showed hepatic progenitor cell-like traits
      including the abilities to self-renew and differentiate and tumorigenicity in
      NOD/SCID mice. Differences were observed in the expression of 421 genes related
      to stem cell signaling pathways (fc >= 2 or fc <= 0.5), among which 231 genes
      were upregulated and 190 genes were downregulated. CONCLUSION: NCAM + c-Kit +
      subset cells in RBE may have properties of hepatic progenitor cells. NCAM
      combined with c-Kit may be a valuable marker for isolating and purifying ICC
      stem/progenitor cells.

PMID- 30301636
TI  - A potential clinical significance of DAB2IP and SPRY2 transcript variants in
      prostate cancer.
AB  - Deregulation of key signaling pathways is one of the primary phenomena in
      carcinogenesis. DAB2IP and SPRY2 are regulatory elements, which act as feedback
      inhibitors of receptor tyrosine kinases signaling in mitogen-activated protein
      kinase pathway. These elements have also been implicated in the pathophysiology
      of cancer. Therefore, this study is aimed to investigate the expression of all
      known splice variants of DAB2IP and SPRY2 in prostate tissue. Fresh Prostate
      tissue samples (50 prostate cancer/ matched normal tissue and 30 BPH) were
      collected and total RNA was extracted followed by cDNA synthesis. The expression
      of DAB2IP and SPRY2 transcript variants were evaluated using RT-PCR and
      quantitative Real-time PCR. The results indicated significant down-regulation of
      DAB2IP transcript variant 1 in cancerous tissues compared to paired normal
      tissues (P = 0.001) as well as SPRY2 transcript variant 2 in cancerous tissues in
      comparison with the normal counterparts and BPH (P = 0.008 and P = 0.025,
      respectively). In addition, there was a significant negative correlation between
      DAB2IP.1 and SPRY2.2 expression with PSA levels in prostate cancer (P = 0.039 rho
      =-0.24 and P = 0.045 rho =-0.3, respectively). Interestingly, the down-regulation
      of DAB2IP.1 mRNA and SPRY2.2 mRNA was positively correlated in tumor samples (P =
      0.002 rho = 0.434). For the first time, this experiment highlights the
      deregulation of DAB2IP and SPRY2 transcript variants in human prostate cancer.
      The present study confirms and extends the previous reports through indicating
      transcript-specific down-regulation and significant association of DAB2IP and
      SPRY2 in prostate tumorigenesis.

PMID- 30301638
TI  - Restricted self-diffusion of adsorbed water in MIL-100(Al).
AB  - An extended two-site exchange model is presented, which is used to evaluate
      pulsed field gradient (PFG) nuclear magnetic resonance (NMR) measurements of
      water in the nanoporous metal-organic framework MIL-100(Al). Here the water
      molecules exchange between the inter- and the intracrystalline space during the
      observation time, but are also restricted in their movement by the crystal
      surface. The evaluation of temperature and loading dependent PFG NMR data yields
      information about the intracrystalline diffusion process, the radius of the
      restricting geometry and the time constants of the exchange process. The
      intracrystalline mean residence time is found to decrease with increasing
      temperature, which allows an estimate of the heat of adsorption under the
      equilibrium conditions of the NMR measurements.

PMID- 30301640
TI  - Clinical Application of Benefit-Finding for Dementia Caregivers.

PMID- 30301639
TI  - In situ reaction monitoring in heterogeneous catalysts by a benchtop NMR
      spectrometer.
AB  - Understanding the reactivity and mass transport properties of porous heterogenous
      catalysts is important for the development of new materials. Whereas MRI has
      previously been used to correlate chemical kinetics and hydrodynamics under
      operando conditions, this paper demonstrates that a modern benchtop NMR
      spectrometer is a suitable alternative to obtain diverse reaction information in
      porous heterogeneous catalyst materials on a smaller scale. Besides information
      about the chemical conversion within the pores, it can also be used to study
      changes of surface interaction by T1/T2 NMR relaxometry techniques and changes in
      mass transport by PFG NMR from a single chemical reaction.

PMID- 30301637
TI  - Large International Validation of ABSIS and PDAI Pemphigus Severity Scores.
AB  - The Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder
      Intensity-Score (ABSIS) scores have been proposed to provide an objective measure
      of pemphigus activity. These scores have been evaluated only on already treated
      patients mainly with mild to moderate activity. The objective was to assess the
      interrater reliability of ABSIS and PDAI scores and their correlation with other
      severity markers in a large international study. Consecutive patients with newly
      diagnosed pemphigus were enrolled in 31 centers. Severity scores were recorded
      during a 24-month period by the same two blinded investigators. Serum was
      collected at each visit for ELISA measurement of anti-desmoglein antibodies. The
      intraclass correlation coefficient (ICC) and Spearman rank correlation
      coefficient were calculated. A total of 116 patients with pemphigus vulgaris (n =
      84) or pemphigus foliaceus (n = 32) were included. At baseline, the ABSIS and
      PDAI ICCs were 0.90 (95% confidence interval [CI] = 0.85-0.93), and 0.91(95% CI =
      0.87-0.94), respectively. The ICCs for PDAI were higher in moderate and extensive
      pemphigus (ICC = 0.82, 95% CI = 0.63-0.92 and ICC = 0.80, 95% CI = 0.62-0.90,
      respectively) than in patients with intermediate (significant) extent (ICC =
      0.50, 95% CI = 0.27-0.68). Conversely, the ICCs for ABSIS were lower in patients
      with moderate extent (ICC = 0.44, 95% CI = 0.004-0.74) than in those with
      intermediate or extensive forms, (ICC = 0.69, 95% CI = 0.51-0.81 and ICC = 0.75,
      95% CI = 0.51-0.88, respectively). During patients' follow-up, the ICCs of both
      ABSIS and PDAI scores remained higher than 0.70. ABSIS and PDAI skin (r = 0.71
      and r = 0.75) but not mucosal (r = 0.32 and r = 0.37) subscores were correlated
      with the evolution of anti-DSG1 and anti-DSG3 ELISA values, respectively. ABSIS
      and PDAI scores are robust tools to accurately assess pemphigus activity.

PMID- 30301641
TI  - Impact of rotavirus vaccine introduction and genotypic characteristics of
      rotavirus strains in children less than 5 years of age with gastroenteritis in
      Ethiopia: 2011-2016.
AB  - INTRODUCTION: A monovalent rotavirus vaccine was introduced in the Ethiopian
      Expanded Program on Immunization from November 2013. We compared impact of
      rotavirus vaccine introduction on rotavirus associated acute diarrhea
      hospitalizations and genotypic characteristics of rotavirus strains pre-and post
      vaccine introduction. METHODS: Sentinel surveillance for diarrhea among children
      <5 years of age was conducted at 3 hospitals in Addis Ababa, Ethiopia from 2011
      to 2017. Stool specimens were collected from enrolled children and tested using
      an antigen capture enzyme immunoassay. Rotavirus positive samples (156 from pre-
      and 141 from post-vaccination periods) were further characterized by rotavirus
      genotyping methods to identify the predominant G and P types circulating during
      the surveillance era. RESULTS: A total of 788 children were enrolled during the
      pre- (July 2011-June 2013) and 815 children during the post-vaccination (July
      2014-June 2017) periods. The proportion of diarrhea hospitalizations due to
      rotavirus among children <5 years of age declined by 17% from 24% (188/788) in
      the pre-vaccine period and to 20% (161/185) in post-vaccine introduction era.
      Similarly, a reduction of 18% in proportion of diarrhea hospitalizations due to
      rotavirus in children <12 months of age in the post (27%) vs pre-vaccine (33%)
      periods was observed. Seasonal peaks of rotavirus declined following rotavirus
      vaccine introduction. The most prevalent circulating strains were G12P[8] in 2011
      (36%) and in 2012 (27%), G2P[4] (35%) in 2013, G9P[8] (19%) in 2014, G3P[6] and
      G2P[4] (19% each) in 2015, and G3P[8] (29%) in 2016. DISCUSSION: Following
      rotavirus vaccine introduction in Ethiopia, a reduction in rotavirus associated
      hospitalizations was seen in all age groups with the greatest burden in children
      <12 months of age. A wide variety of rotavirus strains circulated in the pre- and
      post-vaccine introduction periods.

PMID- 30301642
TI  - The effect of exercise on local and systemic adverse reactions after vaccinations
      - Outcomes of two randomized controlled trials.
AB  - INTRODUCTION: An adverse reaction associated with vaccination is considered to be
      a key barrier to vaccinate, yet little attention has been given to interventions
      to reduce their occurrence. Exercise is a behavioural adjuvant which may also
      influence adverse reactions. Here, two randomized controlled trials are reported,
      examining the effects of exercise on self-reported adverse reactions following
      vaccination in adolescents and young adults. METHODS: Study one; 116 adolescents
      receiving the HPV vaccine were randomly allocated to either Control (n = 56) or
      Pre-vaccine Exercise (n = 60) group (2015-2016). Exercise consisted of 15-minutes
      upper body exercise. Study two; 78 young adults receiving the influenza vaccine
      were randomly allocated to either Control (n = 19), or one of 3 exercise groups:
      Pre-vaccine Arm (n = 19), Pre-vaccine Leg (n = 20) or Post-vaccine Arm (n = 20)
      (2017). Exercise included 15-minutes of arm or leg exercises prior to or after
      vaccination. All participants in both studies completed an adverse events diary
      for seven-days post-vaccination. RESULTS: Study one; Reported days of tenderness
      in female adolescents that exercised were significantly lower than control (p =
      0.032), with a similar trend in reported days of pain (p = 0.050). Furthermore,
      days of feeling ill (p = 0.070) and reduced appetite (p = 0.067) were found to be
      lower with exercise, although not significant. Overall, female adolescents
      reported significantly more days of pain (p = 0.003), tenderness (p < 0.001),
      swelling (p = 0.011), and feeling ill (p = 0.0040). Study two; Exercise groups
      reported reduced days of swelling (p = 0.018), fever (p = 0.013), and lowered
      appetite (p = 0.011) across both genders. Furthermore, females reported reduced
      days of medication use with exercise (p = 0.034), and a trend toward reduced days
      of swelling (p = 0.052). DISCUSSION: In two separate trials, a short bout of
      exercise reduced reported adverse reactions after vaccinations for local and
      systemic adverse reactions. Gender differences in reported local and systemic
      adverse reactions were more evident among adolescents than young adults. These
      findings support the need for further work to examine the potential benefit of
      exercise in improving vaccination procedures.

PMID- 30301643
TI  - Posterior Interosseous Nerve Proximity to Cortical Button Implant for Distal
      Biceps Repair With Single and 2-Incision Approaches.
AB  - PURPOSE: Fixation with a cortical button is the biomechanically strongest
      surgical approach for distal biceps repair, and utilization of the 2-incision
      approach may provide a more anatomical repair and improved terminal supination
      strength. The risk of injury to the posterior interosseous nerve (PIN) associated
      with this approach requires further investigation. METHODS: A distal biceps
      repair with a cortical button was performed on 10 cadavers, 5 utilizing the
      single-incision approach and 5 utilizing the 2-incision approach. Contrast was
      injected into the radial nerve and computed tomography scans were obtained. The
      distance between the drilled cortical perforation and the PIN was measured.
      RESULTS: The mean distance from the cortical perforation to the PIN was not
      significantly different between approaches (9.4 mm and 8.8 mm). A PIN entrapment
      was seen in 0 out of 5 for the single-incision approach and 1 out of 5 for the 2
      incision approach. CONCLUSIONS: Distal biceps repair with cortical button
      fixation places the PIN at risk of injury regardless of the approach used.
      Methods of fixation that require bicortical drilling should be especially avoided
      when using the 2-incision approach. CLINICAL RELEVANCE: Distal biceps repair
      utilizing bicortical drilling for fixation through a 2-incision approach poses
      high risk of injury to the PIN and should be avoided.

PMID- 30301644
TI  - Morphological Changes of the Median Nerve Within the Carpal Tunnel During Various
      Finger and Wrist Positions: An Analysis of Intensive and Nonintensive Electronic
      Device Users.
AB  - PURPOSE: To investigate the effects of static hand postures during various finger
      and wrist positions on morphological changes of the median nerve within the
      carpal tunnel in intensive and nonintensive electronic device users. METHODS:
      Forty-eight university students, equally divided into intensive and nonintensive
      users (>=5 h/d and <5 h/d of electronic device usage, respectively), were
      randomly selected after questionnaire responses and evaluated clinically and by
      ultrasonography. RESULTS: Intensive users reported more wrist/hand pain with a
      high severity score than nonintensive users. They also had larger median nerve
      cross-sectional areas, flattening ratios, and perimeters than nonintensive users,
      and showed less median nerve deformation under various finger and wrist
      positions. Compared with the neutral wrist position with all fingers extended for
      both intensive and nonintensive users, the cross-sectional areas decreased under
      finger flexion and grip, as well as wrist extension-flexion and radial-ulnar
      deviation. Overall, the average median nerve size of the dominant hand was much
      larger than that of the nondominant hand, especially for intensive users.
      CONCLUSIONS: Wrist deviation from neutral can lead to more pronounced deformation
      of the median nerve than finger flexion for both intensive and nonintensive
      users. To minimize compression on the median nerve, it is important to keep the
      wrist as near to the neutral position as possible during computer-related work
      and avoid keeping the thumb and fingers in a static flexed position when using
      mobile devices, especially for single-hand use. CLINICAL RELEVANCE: On the basis
      of this observational study, intensive users had enlarged and flattened median
      nerves as well as decreased nerve deformation during hand motions compared with
      nonintensive users. As overuse of electronic devices may adversely affect the
      median nerve, caution may be warranted.

PMID- 30301645
TI  - In Vivo Survival of Mesenchymal Stromal Cell-Enhanced Decellularized Nerve Grafts
      for Segmental Peripheral Nerve Reconstruction.
AB  - PURPOSE: Adipose-derived mesenchymal stromal cells (MSCs) have emerged as
      promising tools for peripheral nerve reconstruction. There is a paucity of
      information regarding the ultimate survivorship of implanted MSCs or whether
      these cells remain where they are placed. The aim of the present study was to
      track the in vivo distribution and survival of MSCs seeded on a decellularized
      nerve allograft reconstruction of a peripheral nerve defect using luciferase
      based bioluminescence imaging (BLI). METHODS: To determine the in vivo
      survivability of MSCs, autologous Lewis rat MSCs were stably labeled with
      luciferase by lentiviral particles. Labeled cells were dynamically seeded onto a
      Sprague Dawley decellularized rat nerve allograft and used to bridge a 10-mm
      sciatic nerve defect. The MSC survival was determined by performing in vivo BLI
      to detect living cells. Twelve animals were examined at 24 hours after
      implantation, 3, 7, 9, 11, and 14 days, and at daily intervals thereafter if
      signals were still present. RESULTS: Labeled MSCs could be detected for up to 29
      days. Gradually diminishing BLI signals were observed within the first week
      following implantation. Implanted MSCs were not detected anywhere other than the
      site of surgery. CONCLUSIONS: The MSCs seeded on decellularized nerve allografts
      can survive in vivo but have finite survival after implantation. There was no
      evidence of migration of MSCs to surrounding tissues. CLINICAL RELEVANCE: The
      findings support a therapeutic approach that combines MSCs with a biological
      scaffold for peripheral nerve surgery. It provides understanding of the viability
      and distribution of implanted MSCs, which is a prerequisite before clinical
      translation can be considered.

PMID- 30301648
TI  - Stable and efficient partial nitritation granular sludge reactor treating
      domestic sewage at low temperature.
AB  - The success of combined partial nitritation (PN) and anammox process treating low
      strength domestic wastewater depends on achieving a stable and efficient PN. In
      this study, desirable PN for domestic sewage with low temperature of 11.8-16.9 
      degrees C was achieved in a granular sludge reactor operated in anaerobic/aerobic
      (A/O) mode. Average nitrite accumulation ratio of 97.3% was obtained with an
      effluent nitrite/ammonium ratio of 1.2 for influent ammonium of 39.3-78.7 mg.L-1.
      Quantitative microbial analysis and activity batch test showed that nitrite
      oxidizing bacteria (NOB) were effectively suppressed, while ammonium oxidizing
      bacteria (AOB) were dominant. For the efficient suppression of NOB, A/O mode,
      aerobic phosphorus uptake and granular sludge could play important roles.
      Furthermore, high AOB activity was obtained with an average ammonium oxidation
      rate of 11.6 mg N.L-1.h-1, which could be due to the abundant psychrotolerant
      microorganisms, increased content of extracellular polymeric substances and
      relatively high dissolved oxygen condition of the reactor.

PMID- 30301646
TI  - Overstuffing of Unstable Scaphoid Nonunions: A Radiographic Analysis of Carpal
      Parameters.
AB  - PURPOSE: The purpose of this study was to radiographically evaluate scaphoid
      length and carpal parameters before and after reconstruction of nonunions with
      interposition vascularized medial femoral condyle (MFC) bone graft to determine
      if the scaphoid was overstuffed or if normal anatomy was restored and to
      determine the effect on ulnar carpal translocation when the volar radiocarpal
      ligaments were left unrepaired. METHODS: Thirty-nine patients with established
      scaphoid nonunions with carpal collapse were reconstructed by interposition
      vascularized MFC bone grafts without repair of the volar radiocarpal ligaments.
      Pre- and postoperative radiographs and computed tomography scans of the 39
      patients were reviewed. The scaphoid length, capitate-ulnar distance ratio
      (CUDR), modified carpal height ratio (MCHR), radiolunate (RL) and scapholunate
      (SL) angles were measured before and 3 months after surgery. Thirteen of these
      patients had contralateral wrist radiographs that were used for analysis of
      scaphoid length restoration. RESULTS: No significant changes were observed for
      CUDR and MCHR before and after surgery. The length of the scaphoid significantly
      improved after reconstruction from 21.9 +/- 3.3 to 23.7 +/- 3.4 mm on
      posteroanterior x-ray views and from 24.0 +/- 2.2 to 27.7 +/- 2.8 mm on lateral
      views. The RL and SL angles also changed significantly after surgery from 19.5
      degrees  +/- 13.5 degrees  to 4.1 degrees  +/- 16.9 degrees  and from 67.5
      degrees  +/- 12.5 degrees  to 56.0 degrees  +/- 12.5 degrees , respectively.
      Regarding the 13 patients with contralateral x-rays, no differences were seen on
      CUDR, MCHR, or scaphoid length on posteroanterior x-ray views. However, the
      scaphoid length on lateral x-ray views increased from 23.1 +/- 2.40 to 27.6 +/-
      2.78 mm and was significantly longer than the contralateral side by 9.6%. The RL
      and SL angles were restored and comparable with the contralateral side.
      CONCLUSIONS: The use of vascularized MFC bone graft increased scaphoid length by
      9.6% and restored normal carpal alignment. Despite the increased scaphoid length
      compared with the contralateral side, the lack of repair of the volar radiocarpal
      ligaments did not cause ulnar carpal translocation in short-term follow-up. TYPE
      OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 30301647
TI  - In vitro Evidence of Improved Antimicrobial Efficacy of Silver and Triclosan
      Containing Vascular Grafts Compared with Rifampicin Soaked Grafts.
AB  - OBJECTIVES: The aim was to compare the antimicrobial efficacy of four different
      grafts: a standard graft (Intergard, IG), an IG graft soaked in rifampicin
      (IGrif), a silver impregnated graft (Intergard Silver, IGS), and a silver +
      triclosan impregnated graft (Intergard Synergy, IGSy). METHODS: This was a seven
      day in vitro study. The IG, IGrif, IGS, and IGSy grafts were each contaminated
      separately with the following microorganisms: Staphylococcus epidermidis,
      Methicillin resistant Staphylococcus aureus (MRSA), Escherichia coli, and Candida
      albicans from both clinical and American Type Culture Collection (ATCC) origins.
      The in vitro antimicrobial efficacy was evaluated by time to kill assays at T0,
      T24h, T48h, T72h, and T168h. Bactericidal activity was defined as >3 log10
      reduction factor (logRF). Additionally, Rifampicin, triclosan and silver
      resistance development were screened. RESULTS: As anticipated for the non
      antimicrobial IG, all microorganism strains proliferated. The IGSy and the IGS
      showed a seven day bactericidal efficacy (>3 logRF) for all tested
      microorganisms. This efficacy was confirmed at all time points for IGSy only,
      demonstrating faster bactericidal efficacy than IGS. The IGrif demonstrated a
      seven day bactericidal efficacy against the ATCC MRSA only, while showing no
      activity against C. albicans and ATCC E. coli. Regarding ATCC S. epidermidis,
      clinical MRSA and clinical E. coli, IGrif, although bactericidal at earlier time
      points, lost its antimicrobial efficacy at seven days leading to the emergence of
      rifampicin resistant mutants in four of six, two of six, and two of six assays,
      respectively. Mutant strains were also detected in ATCC MRSA in one of six
      assays. No triclosan or silver resistance has emerged at T7days. CONCLUSION: For
      all microorganisms tested, the Synergy graft combining silver with triclosan
      demonstrated a more sustainable and efficient seven day antimicrobial activity
      than the rifampicin soaked graft. The emergence of rifampicin resistant mutants
      suggests preference for a Synergy graft over a graft soaked in rifampicin, to
      prevent or treat an infection when a biological solution is not feasible.

PMID- 30301649
TI  - The association of variables of fibular reconstructed mandible and bite force in
      oral cancer patients with dental implant rehabilitation.
AB  - PURPOSE: The aim of this study was to investigate how the physical variables of
      fibular reconstructed mandibles with dental implants affects the relative bite
      force in oral cancer patients. MATERIALS AND METHODS: Over 7 years of follow-up,
      13 oral cancer patients were enrolled who included 51 successful implants in the
      fibular flap. The tactile sensor analyzer evaluated the bite force. The crown
      implant ratio, fibular, and rehabilitated dental length were measured using
      radiographic images. Linear regression was used to analyze the bite force related
      to the variables of the implants in the fibular reconstructed mandible. RESULTS:
      Even when the results showed no statistical significance (P > 0.05), increasing
      the crown-implant ratio, length of the fibular flap, and implant prosthetic
      reconstructed dentition had a tendency to decrease the bite force (estimate from 
      0.08% to -4.27%); there was a positive trend of occlusal force and the length of
      rehabilitative dentition compared with the dental antagonist (estimate = 6.95).
      CONCLUSION: In this study, the crown-implant ratio, implant dentition, and
      fibular flap length revealed no significant impact on the bite force or implant
      success in oral cancer patients; however, a trend to weaken the bite force was
      suggested once the numerical values of these variables increased.

PMID- 30301650
TI  - Effects of systemic erythropoietin treatment and heterogeneous xenograft in
      combination on bone regeneration of a critical-size defect in an experimental
      model.
AB  - The aim of the present study was to evaluate the effects of systemic EPO
      treatment alone or in combination with xenogenic bone graft augmentation on bone
      regeneration. Eleven adult male Sprague-Dawley rats were used in the present
      study. Rats were subjected to bilateral 5 mm critical size bone defects on the
      parietal bones under general anaesthesia. Right parietal bone defects were
      augmented with xenogenic bone graft and left parietal bone defect was left empty.
      Rats were randomly assigned for one of the two groups. One group of rats received
      (i) vehicle (n = 6) and other group received (ii) EPO (500IU kg/day) (n = 5). EPO
      treatment was continued for 28 days. Vascularization was analysed by
      immunohistochemical staining of CD31 (PECAM-1) and new bone formation was
      histomorphometrically evaluated. Xenogenic graft augmentation enhanced bone
      formation and vascularization significantly in either vehicle or EPO treated
      groups (p < 0.05). Histomorphometric results of angiogenesis was similar in the
      EPO treated group and the control group. However, angiogenesis was significantly
      higher in the combination of systemic EPO treatment with graft augmentation than
      graft augmentation alone (p < 0.01). Graft augmentation for treatment of critical
      size bone defects seems essential for proper bone healing. Results of the present
      study suggest that EPO potentiates the regenerative processes of augmented bone
      defects.

PMID- 30301651
TI  - Relapse tendency after BSSO surgery differs between 2D and 3D measurements: A
      validation study.
AB  - Bilateral sagittal split ramus osteotomy (BSSO) surgery is used to correct
      various dento-skeletal deformities. Clinical outcomes are critically dependent on
      accurate and proper positioning of skeletal units created by BSSO. Monitoring
      skeletal changes postoperatively is a major part of follow-up. Between January
      2015 and December 2015, 24 patients underwent BSSO surgery without any other
      segmental osteotomy (mean age, 29.9 +/- 14.2 [range, 17-67] years; 18 females).
      Cephalometric X-rays and cone-beam computed tomography scans were performed 6
      weeks and 12 months postoperatively. We compared the position displacement at
      three mandibular points at both postoperative time points using 2- and 3
      dimensional analysis separately and examined the relationship between these
      methods. Horizontally in at least in 14/24 patients, the difference between 2
      dimensional and 3-dimensional measurements was >1 mm. Vertically in at least in
      16/24 patients, the difference between 2-dimensional and 3-dimensional
      measurements was >1 mm. A scatter plot with orthogonal regression indicated the
      relationships between the 2-dimensional measurement and the corresponding 3
      dimensional measurement in the horizontal and vertical directions. Skeletal
      relapse with 2-dimensional-measurements differed significantly from the 3
      dimensional measurements. There was no evidence of a relationship between the two
      types of measurements regarding the direction and the location of the landmarks.

PMID- 30301652
TI  - Visualization and quantification of tongue movement during articulation: Is
      ultrasound a valid alternative to magnetic resonance imaging?
AB  - BACKGROUND: Quality of life in tumour patients following combined ablative and
      reconstructive head and neck surgery varies significantly. This is at least
      partially due to differences in speech and swallowing function. A tool to
      objectively evaluate articulation by magnetic resonance imaging (MRI) has now
      been tested alongside ultrasound examination. PATIENTS AND METHODS: A
      standardized sequence of phonemes from the German language was established in 20
      healthy volunteers and recorded in different planes by MRI and ultrasound.
      Phonemes were identified through recognition of typical tongue configurations by
      two different observers. An algorithm for metric analysis of articulation in
      terms of distances and angles for five extreme points on the tongue (anterior,
      posterior, cranial and two basal corners) was designed. The findings in these
      volunteers were subsequently compared with the results of an examination of a
      tumour patient. RESULTS: Physiological articulation was visualized and evaluated
      both by MRI and ultrasound. There was a high intra-class correlation coefficient
      for measurements between independent observers. Tongue position for certain
      phonemes was mostly constant in healthy patients of different age groups, with
      gender-specific differences. In a first comparison, tongue position in a patient
      with tongue cancer differed significantly from this position, both pre- and
      postoperatively. In agreement with clinical articulation quality, the tongue
      position of the patient returned to almost normal within 12 months
      postoperatively. CONCLUSION: Both ultrasound and MRI are appropriate instruments
      for visualization of articulation and objective measurements to evaluate speech
      in tumour patients. Whilst MRI is more precise and can identify more subtle
      differences, ultrasound is a valid alternative due to its wider availability and
      broader applicability.

PMID- 30301653
TI  - An introduction to the electronic waterpipe.
AB  - Despite the associated negative health outcomes, waterpipe smoking remains a
      popular method of tobacco consumption, specifically in young adults. While there
      have been expanding efforts to decrease waterpipe use, there is a new, non
      combustible waterpipe device on the market, the electronic waterpipe (e
      waterpipe), that could serve as an alternative to traditional, combustible
      waterpipe smoking. There is currently no known literature evaluating the e
      waterpipe including prevalence of use or its health risks. This mini review
      defines the e-waterpipe, explains how an e-head is used to construct an e
      waterpipe, and describes the various e-head models available for use. The review
      also discusses implications of e-head use and provides recommendations for future
      research and regulation.

PMID- 30301654
TI  - Using public health surveillance data to measure Clostridium difficile infection
      population burden in Massachusetts.
AB  - Clostridium difficile occurs both inside and outside of health care facilities,
      but surveillance has been traditionally limited to the hospital setting. To
      measure the population-based burden of C difficile infection (CDI), we used
      multiple routine sources of data. We found an overall rate of CDI in
      Massachusetts in 2016 of 132.5 per 100,000 population, with mortality in 2014 of
      6.4 per 100,000 population. Population-based measurement of CDI burden appears
      feasible without conducting a special study.

PMID- 30301655
TI  - Effect of varying federal definitions on prevalence and characteristics
      associated with carbapenem-resistant Enterobacteriaceae in veterans with spinal
      cord injury.
AB  - BACKGROUND: Patients with spinal cord injury (SCI) have a high risk for multidrug
      resistant organisms, including carbapenem-resistant Enterobacteriaceae (CRE).
      Accurate and easily applied definitions are critical to identify CRE. This study
      describes CRE and associated characteristics in veterans with SCI per Centers for
      Disease Control and Prevention (CDC) and Department of Veterans Affairs (VA)
      definitions. METHODS: A retrospective cohort of veterans with SCI and more than 1
      culture with Escherichia coli, Klebsiella spp and/or Enterobacter spp between
      2012 and 2013 was examined. Antibiotic susceptibility criteria of pre-2015 (CDC1)
      and post-2015 (CDC2) CDC definitions and pre-2017 (VA1) and post-2017 (VA2) VA
      definitions were used to identify CRE. CRE prevalence and characteristics are
      described for isolates meeting each definition, and agreement was assessed with
      the Cohen kappa. RESULTS: We reviewed 21,514 isolates cultured from 6,974
      veterans; 423 isolates met any CRE definition. Although agreement among
      definitions was high (kappa = 0.82-0.93), definitions including ertapenem
      resistance led to higher CRE prevalence (VA1 = 1.7% and CDC2 = 1.9% vs VA2 = 1.4%
      and CDC1 = 1.5%). Forty-four of 142 VA facilities had more than 1 CRE case
      defined by VA2; 10 facilities accounted for 60% of CRE cases. Almost all CRE was
      isolated from high-complexity, urban facilities, and the South had the highest
      proportion of CRE. CONCLUSIONS: Varying federal definitions give different CRE
      frequencies in a high-risk population. Definitions including ertapenem resistance
      resulted in higher CRE prevalence but may overemphasize noncarbapenemase
      isolates. Thus, both federal definitions now highlight the importance of
      carbapenemase testing.

PMID- 30301656
TI  - A novel personal protective equipment coverall was rated higher than standard
      Ebola virus personal protective equipment in terms of comfort, mobility and
      perception of safety when tested by health care workers in Liberia and in a
      United States biocontainment unit.
AB  - BACKGROUND: During the 2014-2016 Ebola virus epidemic, more than 500 health care
      workers (HCWs) died in spite of the use of personal protective equipment (PPE).
      The Johns Hopkins University Center for Bioengineering Innovation and Design
      (CBID) and Jhpiego, an international nongovernmental organization affiliate of
      Johns Hopkins, collaborated to create new PPE to improve the ease of the doffing
      process. METHODS: HCWs in Liberia and a US biocontainment unit compared standard
      Medecins Sans Frontiere PPE (PPE A) with the new PPE (PPE B). Participants wore
      each PPE ensemble while performing simulated patient care activities. Range of
      motion, time to doff, comfort, and perceived risk were measured. RESULTS:
      Overall, 100% of participants preferred PPE B over PPE A (P < .0001); 98.1% of
      respondents would recommend PPE B for their home clinical unit (P < .0001). There
      was a trend towards greater comfort in PPEB. HCWs at both sites felt more at risk
      in PPE A than PPE B (71.9% vs 25% in Liberia, P < .0001; 100% vs 40% in the US
      biocontainment unit, P < .0001). CONCLUSIONS: HCWs preferred a new PPE ensemble
      to Medecins Sans Frontiere PPE for high-consequence pathogens. Further studies on
      the safety of this new PPE need to be conducted.

PMID- 30301657
TI  - Laxative use and testing for Clostridium difficile in hospitalized adults: An
      opportunity to improve diagnostic stewardship.
AB  - BACKGROUND: It is recommended that that only unformed stool from patients with
      diarrhea be tested for Clostridium difficile infection. We determined the
      prevalence of and patient characteristics associated with antecedent laxative
      receipt among hospitalized adults undergoing C difficile testing. METHODS: In a
      case-control study of 5,452 C difficile tests from 5 hospitals in Southeast
      Michigan, patients who received laxatives (docusate, senna, polyethylene glycol
      3350, bisacodyl, and magnesium hydroxide) in the 24 or 48hours before testing
      were identified. Logistic regression was performed to identify patient
      characteristics associated with laxative receipt before testing. RESULTS: In 535
      (9.8%) and 707 (13%) tests, patients received laxatives in the 24 and 48hours
      before testing, respectively. The odds of antecedent laxative receipt were
      significantly greater for patients residing on a surgical service than a medical
      service (24hours odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-3.1;
      48hours OR, 2.7; 95% CI, 2.3-3.2), patients residing in an intensive care unit
      (ICU) than a non-ICU (24hours OR, 1.3; 95% CI, 1.0-1.6; 48hours OR, 1.3; 95% CI,
      1.1-1.6), and patients whose Elixhauser Comorbidity Score was 4 or higher
      (24hours OR, 1.4; 95% CI, 1.1-1.7; 48hours OR, 1.4; 95% CI, 1.2-1.7).
      CONCLUSIONS: Among patients tested for C difficile, antecedent laxative use was
      common. Improving diagnostic stewardship around C difficile testing, particularly
      in surgical and ICU patients, is a significant opportunity and priority for
      quality improvement.

PMID- 30301658
TI  - The role of short-term weather conditions in temporal dynamics of fire regime
      features in mainland Spain.
AB  - In this paper we investigate spatial-temporal associations of fire weather danger
      and fire regime features from 1979 to 2013. We analyze monthly time series of
      fire activity (number of fires and burned area) and fire weather danger rating
      indices (Fire Weather Index, Burning Index and Forest Fire Danger Index) at two
      spatial scales: (i) regionally, splitting the Spanish mainland into Northwest,
      Hinterland and Mediterranean regions; and (ii) locally, using the EMCWF grid. All
      analyses are based on decomposing time series to retrieve differential indicators
      of seasonal cycles, temporal evolution and anomalies. At regional scale we apply
      lagged cross-correlation analysis (4 lags or months before fire) to explore
      seasonal associations; and trend detection tests on the temporal evolution
      component. At the local scale, we calculate Pearson correlation coefficients
      between each individual index and the 18 possible fire-activity subsets according
      to fire size (all sizes, >1 ha and >100 ha) and source of ignition (natural,
      unintended and arson); this analysis is applied to both cycles, temporal and
      anomalies series. Results suggest that weather controls seasonal fire activity
      although it has limited influence on temporal evolution, i.e. trends. Stronger
      associations are detected in the number of fires in the Northwest and Hinterland
      regions compared to the Mediterranean, which has desynchronized from weather
      since 1994. Cross-correlation analysis revealed significant fire-weather
      associations in the Hinterland and Mediterranean, extending up to two months
      prior fire ignition. On the other hand, the association between temporal trends
      and weather is weaker, being negative along the Mediterranean and even
      significant in the case of burned area. The spatial disaggregation into grid
      cells reveals different spatial patterns across fire-activity subsets. Again, the
      connection at seasonal level is noticeable, especially in natural-caused fires.
      In turn, human-related wildfires are occasionally found independent from weather
      in some areas along the northern coast or the Ebro basin. In any case, this
      effect diminishes as the size of the fire increases. Our work suggests that for
      some regions of mainland Spain, these fire danger indices could provide useful
      information about upcoming fire activity up to two months ahead of time and this
      information could be used to better inform wildland fire prevention and
      suppression activities.

PMID- 30301659
TI  - An investigation on the capability of magnetically separable Fe3O4/mordenite
      zeolite for refinery oily wastewater purification.
AB  - Damage to the water resources and environment as a consequence of oil production
      and use of fossil fuels, has increased the need for applying various technologies
      and developing effective materials to remove contaminates from oily wastewaters
      resources. One of the challenges for an economic industrial wastewater treatment
      is separation and reusability of the developed purifying agents. Development of
      magnetic materials could potentially facilitate easier and more economic
      separation of purifying agents. Therefore, herein we have synthesised an
      efficient and easily recyclable Fe3O4/mordenite zeolite using a hydrothermal
      process to investigate its purification capability for wastewater from Kermanshah
      oil refinery. The synthesised Fe3O4/mordenite zeolite was characterised using
      XRD, FTIR, SEM, EDX, XRF and BET analysis. XRD result showed that the synthesised
      Fe3O4/mordenite zeolite comprised sodium aluminium silicate hydrate phase [01-072
      7919, Na8(Al6Si30O72)(H2O)9.04] and cubic iron oxide phase [04-013-9808, Fe3O4].
      Response Surface Method (RSM) combined with Central Composite Design (CCD) was
      used to identify the optimum operation parameters of the pollutant removal
      process. The effect of pH, contact time and Fe3O4/mordenite zeolite amount on the
      Chemical Oxygen Demand (COD), Biochemical Oxygen Demand (BOD) and Nephelometric
      Turbidity Unit (NTU) were investigated. It was found that pH was the most
      significant factor influencing COD and BOD removal but the quantity of
      Fe3O4/mordenite zeolite was the most influential factor on the turbidity removal
      capacity. The optimum removal process conditions were identified to be pH of
      7.81, contact time of 15.8 min and Fe3O4/mordenite zeolite amount of 0.52% w/w.
      The results show that the regenerated Fe3O4/mordenite zeolite can be reused for
      five consecutive cycles in purification of petroleum wastes.

PMID- 30301660
TI  - Treatment of older patients with advanced non-small cell lung cancer: A
      challenge.
AB  - With a median age of 70 years at diagnosis, lung cancer is a disease of older
      persons. As a consequence oncologists are confronted with an increasing older
      lung cancer population for which treatment decisions are needed. In the past
      years, the therapeutic landscape of advanced non-small cell lung cancer (NSCLC)
      has changed impressively with the introduction of targeted therapies and
      immunotherapy next to chemotherapy. Treatment choices for advanced NSCLC are
      mainly guided by different tumor-related characteristics. However, in older
      patients treatment decisions are more complex because of the scarcity of data
      from large randomized studies in older patients and the heterogeneity of this
      population with regards to different geriatric domains such as functional status,
      comorbidity and polypharmacy. The present manuscript reviews available data for
      the different treatment options for older patients with NSCLC as well as the use
      of geriatric assessment as an evaluation and guidance tool.

PMID- 30301661
TI  - Comparison of intraperitoneal ropivacaine and bupivacaine for postoperative
      analgesia in dogs undergoing ovariohysterectomy.
AB  - OBJECTIVE: To compare postoperative analgesia following either intraperitoneal
      (IP) ropivacaine or bupivacaine in dogs undergoing ovariohysterectomy (OVH) in
      the scope of multimodal analgesia. STUDY DESIGN: Prospective, randomized, blinded
      clinical study. ANIMALS: A total of 45 privately owned dogs undergoing OVH, aged
      37 +/- 28 months and weighing 11.3 +/- 4.5 kg. METHODS: Dogs were premedicated
      with acepromazine (0.05 mg kg-1) and morphine (0.5 mg kg-1) intramuscularly (IM).
      Anaesthesia was induced with alfaxalone and maintained with isoflurane in oxygen.
      Carprofen (4 mg kg-1) was injected subcutaneously after intubation. Dogs were
      randomly assigned to receive either bupivacaine (group B; 3 mg kg-1) or
      ropivacaine (group R; 3 mg kg-1) IP prior to complete closure of the linea alba.
      At 0.5, 1, 2, 4, 6 and 8 hours after extubation, sedation and postoperative pain
      were assessed, using the short form of the Glasgow Composite Pain scale (GCPS
      SF), a dynamic interactive visual analogue scale (DIVAS), and mechanical
      nociceptive threshold (MNT) measurement. Rescue morphine (0.2 mg kg-1) was
      administered in case of >= 5/20 or >= 6/24 in the GCPS-SF and/or >40 mm in the
      DIVAS. Parametric data were compared using the t test; nonparametric data were
      analysed with the two-sample Wilcoxon test (p < 0.05). RESULTS: The GCPS-SF score
      was significantly higher in group R at 8 hours. There was no other significant
      difference regarding sedation or analgesia between the groups. Rescue analgesia
      was administered to 15 dogs (R: 9/22; B: 6/22), with no significant difference
      between the groups. MNT values decreased in both groups at all time points when
      compared to baseline. No adverse effects were observed. CONCLUSIONS AND CLINICAL
      RELEVANCE: Ropivacaine or bupivacaine IP in combination with morphine IM and
      carprofen SC provided comparable postoperative analgesia in dogs after OVH for 6
      hours. However, the anaesthetic protocol used did not prevent the administration
      of rescue analgesia in 41% of animals.

PMID- 30301662
TI  - Limited fluid volume resuscitation (LFVR) in severe shock unresponsive to initial
      fluid challenge: A pilot study in 10 cats.
AB  - OBJECTIVE: To evaluate the effect of limited fluid volume resuscitation (LFVR)
      administration in cats with severe shock that was unresponsive to initial
      conventional resuscitation (CR) with isotonic crystalloids. STUDY DESIGN:
      Clinical pilot study. ANIMALS: Ten client-owned cats with non-cardiogenic shock,
      unresponsive to CR. METHODS: After an initial ineffective CR with isotonic
      crystalloids (15-20 mL kg-1 in 15 minutes), LFVR was started. The animals were
      randomly assigned to one of two treatments: hypertonic saline alone (group HTS)
      or HTS and hydroxyethyl starch (HES) (group HTS/HES). A first bolus of HTS (2 mL
      kg-1) was administered to both groups, immediately followed by HES (2 mL kg-1) to
      group HTS/HES over 5-10 minutes and vital signs were re-evaluated. Additional
      boluses were administered, every 5-10 minutes, until stabilization (vital
      parameters, such as temperature, heart rate, respiratory frequency, quality of
      the pulse and sensorium within the physiological ranges). The time until
      stabilization (minutes), the volume of HTS and colloid administered and the
      effect of LFVR on vital parameters were determined. RESULTS: A mean +/- standard
      deviation (range) volume of 3 +/- 2 (2-6) mL kg-1 of hypertonic saline in group
      HTS and 4 +/- 2 (2-6) mL kg-1 of both hypertonic and colloidal solutions in group
      HTS/HES was administered. In six cats (60%), a single bolus of HTS alone (group
      HTS; n = 3/4) or in combination with HES (group HTS/HES; n = 3/6) was sufficient
      for stabilization. In the remaining four cases (40%), a second bolus was
      required. Stabilization occurred in 33 +/- 13 minutes (15-60 minutes). Of the 10
      cats, six had a positive outcome (6-24 months follow-up) and the others died
      during hospitalization. CONCLUSIONS AND CLINICAL RELEVANCE: LFVR appears to be an
      efficacious treatment for feline shock and may be an alternative therapy for cats
      unresponsive to CR. Larger cross-sectional and prospective studies are needed to
      confirm these findings.

PMID- 30301663
TI  - Effect of benzodiazepines on the dose of alfaxalone needed for endotracheal
      intubation in healthy dogs.
AB  - OBJECTIVE: To evaluate the dose-sparing effect of midazolam or diazepam on the
      dose of alfaxalone required to achieve endotracheal intubation in premedicated
      dogs. STUDY DESIGN: Prospective, randomized, 'blinded', controlled clinical
      trial. ANIMALS: Ninety healthy dogs anaesthetized for elective surgery or
      diagnostic procedures. METHODS: Saline (0.1 mL kg-1), or midazolam or diazepam
      (0.2, 0.3, 0.4 or 0.5 mg kg-1) intravenously (IV) was randomly assigned;
      investigators were unaware of group designation. After premedication with IV
      acepromazine 0.01 mg kg-1 and methadone 0.2 mg kg-1, the degree of sedation was
      assessed. Alfaxalone (0.5 mg kg-1) was administered IV, followed by the assigned
      treatment. Further alfaxalone was administered until endotracheal intubation
      could be performed. Ease of endotracheal intubation, pulse rate and arterial
      blood pressure were assessed. General linear models were used to examine the
      effect of treatment drug and dose on induction dose of alfaxalone with Tukey's
      post hoc tests. Incidence of adverse reactions was assessed with chi-square
      tests. RESULTS: There were no significant differences between groups with regard
      to demographic data or sedation. Median (range) induction dose of alfaxalone in
      the saline group was 0.74 (0.43-1.26) mg kg-1 compared with 0.5 (0.46-0.75) mg kg
      1 and 0.5 (0.42-1.2) mg kg-1 for the midazolam and diazepam groups, respectively.
      Midazolam 0.3 and 0.5 mg kg-1 (p = 0.005 and 0.044, respectively) and diazepam
      0.4 mg kg-1 (p = 0.032) reduced the alfaxalone dose compared with saline. Adverse
      effects were not significantly different between groups. Midazolam 0.2, 0.3, 0.4
      and 0.5 mg kg-1 (p < 0.044, p = 0.001, p = 0.007, p = 0.044, respectively) and
      diazepam 0.2 and 0.5 mg kg-1 (p = 0.025 and p = 0.025) improved intubation score
      compared with saline. CONCLUSION AND CLINICAL RELEVANCE: Midazolam 0.3 and 0.5 mg
      kg-1 and diazepam 0.4 mg kg-1 coadministered at anaesthetic induction allow
      alfaxalone dose reduction in healthy dogs. Use of benzodiazepines improved the
      ease of endotracheal intubation.

PMID- 30301664
TI  - Metabolic acidosis during general anaesthesia: presumed systemic toxicity caused
      by topical dorzolamide in a dog.

PMID- 30301665
TI  - Sedative effect of intramuscular medetomidine with and without vatinoxan (MK
      467), and its reversal with atipamezole in sheep.
AB  - OBJECTIVE: To evaluate the effect of the peripherally acting alpha2-adrenoceptor
      antagonist vatinoxan (MK-467) on the sedative properties of medetomidine (MED)
      when injected intramuscularly (IM) in the same syringe and on reversal of this
      sedation with atipamezole in sheep. STUDY DESIGN: Randomized, blinded, crossover
      experimental trial. ANIMALS: Eight healthy adult female sheep. METHODS: Sheep
      received MED (30 MUg kg-1 IM) alone or combined in the same syringe with
      vatinoxan (300 MUg kg-1 IM, MED+VAT) with a 2 week washout period. Atipamezole
      (150 MUg kg-1 IM) was administered 30 minutes later for reversal. Sedation was
      assessed using two sedation scores, a visual analog score and a descriptive scale
      before treatments (T0) and at intervals up to 5 hours thereafter. Pulse rate (PR)
      was counted at T0 and at 30 (T30) and 90 (T90) minutes. Rectal temperature was
      measured at T0 and T90 postinjection. Plasma samples were analyzed for drug
      concentrations at T30 and T90. RESULTS: The first signs of sedation were seen
      significantly earlier after MED+VAT (4.6 +/- 1.7 minutes versus 9.4 +/- 2.6
      minutes after MED) and the sedation scores were significantly higher after
      MED+VAT than MED. All animals laid with head down 10.0 +/- 3.4 minutes after
      MED+VAT, whereas three MED animals did not become recumbent before atipamezole
      was administered. The plasma concentrations of dexmedetomidine were significantly
      higher at T30 (2.47 +/- 0.2 ng mL-1) and significantly lower at T90 (1.23 +/- 0.3
      ng mL-1) with MED+VAT than with MED (1.19 +/- 0.8 and 1.83 +/- 0.4 ng mL-1,
      respectively). While no significant differences were observed between treatments
      in PR at T30, PR at T90 was significantly higher with MED+VAT than with MED.
      CONCLUSIONS AND CLINICAL RELEVANCE: When administered IM in the same syringe,
      vatinoxan hastened and intensified the initial sedative effects of MED and
      enhanced the sedation reversal by atipamezole.

PMID- 30301666
TI  - Development of Targeted siRNA Nanocomplexes to Prevent Fibrosis in Experimental
      Glaucoma Filtration Surgery.
AB  - RNAi induced by double-stranded small interfering RNA (siRNA) molecules has
      attracted great attention as a naturally occurring approach to silence gene
      expression with high specificity. The myocardin-related transcription
      factor/serum response factor (MRTF/SRF) pathway is a master regulator of
      cytoskeletal gene expression and, thus, represents a promising target to prevent
      fibrosis. A major hurdle to implementing siRNA therapies is the method of
      delivery, and we have, thus, optimized lipid-peptide-siRNA (LPR) nanoparticles
      containing MRTF-B siRNAs as a targeted approach to prevent conjunctival fibrosis.
      We tested 15 LPR nanoparticle formulations with different lipid compositions,
      surface charges, and targeting or non-targeting peptides in human conjunctival
      fibroblasts. In vitro, the LPR formulation of the DOTMA/DOPE lipid with the
      targeting peptide Y (LYR) was the most efficient in MRTF-B gene silencing and non
      cytotoxic compared to the non-targeting formulation. In vivo, subconjunctival
      administration of LYR nanoparticles containing MRTF-B siRNAs doubled bleb
      survival in a pre-clinical rabbit model of glaucoma filtration surgery.
      Furthermore, MRTF-B LYR nanoparticles reduced the MRTF-B mRNA by 29.6% in rabbit
      conjunctival tissues, which led to significantly decreased conjunctival scarring
      with no adverse side effects. LYR-mediated delivery of siRNA shows promising
      results to increase bleb survival and to prevent conjunctival fibrosis after
      glaucoma filtration surgery.

PMID- 30301667
TI  - miR-30 Family Reduction Maintains Self-Renewal and Promotes Tumorigenesis in
      NSCLC-Initiating Cells by Targeting Oncogene TM4SF1.
AB  - Increasing evidence indicates that tumor-initiating cells (TICs) are responsible
      for the occurrence, development, recurrence, and development of the drug
      resistance of cancer. MicroRNA (miRNA) plays a significant functional role by
      directly regulating targets of TIC-triggered non-small-cell lung cancer (NSCLC),
      but little is known about the function of the miR-30 family in TICs. In this
      study, we found the miR-30 family to be downregulated during the spheroid
      formation of NSCLC cells, and patients with lower miR-30a/c expression had
      shorter overall survival (OS) and progression-free survival (PFS). Moreover,
      transmembrane 4 super family member 1 (TM4SF1) was confirmed to be a direct
      target of miR-30a/c. Concomitant low expression of miR-30a/c and high expression
      of TM4SF1 correlated with a shorter median OS and PFS in NSCLC patients. miR
      30a/c significantly inhibited stem-like characteristics in vitro and in vivo via
      suppression of its target gene TM4SF1, and then it inhibited the activity of the
      mTOR/AKT-signaling pathway. Thus, our data provide the first evidence that TM4SF1
      is a direct target of miR-30a/c and miR-30a/c inhibits the stemness and
      proliferation of NSCLC cells by targeting TM4SF1, suggesting that miR-30a/c and
      TM4SF1 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC
      patients.

PMID- 30301669
TI  - Catheter Ablation of Ventricular Fibrillation.
AB  - Ventricular fibrillation (VF) is a common and life-threatening arrhythmia
      resulting in sudden cardiac death (SCD). Due to the inherent challenges of
      mapping VF in humans, the underlying mechanisms that initiate and sustain this
      common arrhythmia are still poorly understood. In high-risk patients and
      survivors of SCD, implantable cardioverter defibrillators (ICD) play a central
      role in treating VF episodes, however, ICDs do not prevent VF recurrences and
      patients remain at risk of electrical storm and multiple shocks that are often
      refractory to escalation of medical therapy. More recently, the utility of
      catheter ablation (CA) has extended to the treatment of VF storms. This review
      will focus on updates in elucidating the mechanism of VF leading into the role
      and indication of CA as a treatment strategy.

PMID- 30301668
TI  - 4Mu Decreases CD47 Expression on Hepatic Cancer Stem Cells and Primes a Potent
      Antitumor T Cell Response Induced by Interleukin-12.
AB  - The tumor microenvironment (TME) represents a complex interplay between different
      cellular components, including tumor cells and cancer stem cells (CSCs), with the
      associated stroma; such interaction promotes tumor immune escape and sustains
      tumor growth. Several experimental approaches for cancer therapy are focused on
      TME remodeling, resulting in increased antitumor effects. We previously
      demonstrated that the hyaluronan synthesis inhibitor 4-methylumbelliferone (4Mu)
      decreases liver fibrosis and induces antitumor activity in hepatocellular
      carcinoma (HCC). In this work, 4Mu, in combination with an adenovirus encoding
      interleukin-12 genes (AdIL-12), elicited a potent antitumor effect and
      significantly prolonged animal survival (p < 0.05) in an orthotopic HCC model
      established in fibrotic livers. In assessing the presence of CSCs, we found
      reduced mRNA levels of CD133+, CD90+, EpCAM+, CD44+, and CD13+ CSC markers within
      HCC tumors (p < 0.01). Additionally, 4Mu downregulated the expression of the CSC
      marker CD47+ on HCC cells, promoted phagocytosis by antigen-presenting cells,
      and, combined with Ad-IL12, elicited a potent cytotoxic-specific T cell response.
      Finally, animal survival was increased when CD133low HCC cells, generated upon
      4Mu treatment, were injected in a metastatic HCC model. In conclusion, the
      combined strategy ameliorates HCC aggressiveness by targeting CSCs and as a
      result of the induction of anticancer immunity.

PMID- 30301670
TI  - Right Ventricular Function is Associated With Quality of Life in Patients With
      Systemic Lupus Erythematosus Associated Pulmonary Arterial Hypertension.
AB  - BACKGROUND: Right ventricular (RV) function has been identified as an important
      determinant of outcome in patients with pulmonary hypertension. We aimed to
      investigate the relationship between echocardiographic-derived RV function and
      health-related quality of life (HRQOL) in patients with systemic lupus
      erythematosus associated pulmonary arterial hypertension (SLE-APAH), and to
      identify the best echocardiographic parameter for evaluating RV function in these
      patients. METHODS: Sixty consecutive patients with SLE-APAH (all female, mean age
      33.6+/-8.2years) were recruited from May 2013 to November 2014. Echocardiograph,
      right heart catheterisation, SLE disease activity index (SLEDAI), and functional
      status and SF-36 generic questionnaire were assessed. RESULTS: Echocardiograph
      derived RV systolic function was significantly correlated with haemodynamics
      (p<0.05), with tricuspid annular plane systolic excursion (TAPSE) showing the
      strongest correlation with pulmonary vascular resistance (R2=0.278, p<0.001) and
      cardiac index (R2=0.215, p<0.001). Patients with a TAPSE<17mm had a shorter 6
      minute-walk-distance (6MWD), lower mixed venous oxygen saturation, and higher
      plasma N-terminal pro-brain natriuretic peptide (p<0.05). Patients with TAPSE
      <17mm had lower physical component summary (PCS) and mental component summary
      (MCS) scores than those with TAPSE >=17mm (35.5+/-13.2 vs. 55.0+/-15.5; 46.3+/
      15.3 vs. 64.8+/-18.8, respectively, all p<0.05). On multiple regression analysis,
      a TAPSE <17mm was independently related to lower PCS (beta -15.797, 95%
      confidence interval [CI] -24.746 to -6.848, p=0.001) and lower MCS (beta -12.887,
      95% CI -24.018 to -1.755, p=0.024). CONCLUSIONS: TAPSE is a useful index for RV
      function assessment, and is associated with HRQOL in patients with SLE-APAH.

PMID- 30301671
TI  - The Surface Electrocardiograph in Ventricular Arrhythmias: Lessons in
      Localisation.
AB  - The 12-lead electrocardiograph (ECG) is of critical importance both in the
      diagnosis of wide complex tachycardia and in the further classification,
      characterisation and management of ventricular arrhythmias. With its diligent
      application and interpretation, remarkable precision can be achieved in the
      localisation of the site of origin of ventricular arrhythmias and this may have
      major implications in the care of these patients. This review discusses the
      technical, anatomic and mechanistic basis of ECG interpretation in ventricular
      arrhythmias.

PMID- 30301672
TI  - Device-Related Thrombus After Left Atrial Appendage Occlusion With the Amulet
      Device.
AB  - BACKGROUND: Left atrial appendage occlusion (LAAO) is increasingly used for
      stroke prevention in patients with atrial fibrillation who are considered
      unsuitable for a lifelong oral anticoagulant regimen. Recently, a single-centre
      study reported device-related thrombus formation in 16.7% of patients treated
      with the second-generation Amulet device (St. Jude Medical, St. Paul, MN, USA),
      presenting a potential major safety concern. As "real-world" data on device
      related thrombus formation following LAAO with the Amulet occluder are scarce, we
      aimed to evaluate this outcome in a retrospective registry. METHODS: Clinical and
      tranosesophageal echocardiography data after LAAO with the Amulet in consecutive
      patients from three centres were collated. RESULTS: Among 38 patients (mean age
      75.8 years), mean (standard deviation) CHA2DS2-VASc and HAS-BLED scores were 4.4
      (1.2) and 3.4 (0.9), respectively. All patients underwent successful device
      placement without procedure-related adverse events. The antithrombotic regimen at
      discharge consisted of dual antiplatelet therapy (DAPT) in 27 patients (71.1%),
      single antiplatelet therapy in 10 patients (26.3%), and no antithrombotic therapy
      in one patient (2.6%). Device-related thrombus was observed in one patient (2.6%)
      despite DAPT regimen. The outcome of this patient was uncomplicated after
      adjustment of oral anticoagulant therapy. No patients presented with a
      thromboembolic event following LAAO during a mean (standard deviation) follow-up
      of 15 (5) months. CONCLUSIONS: In this retrospective study, device-related
      thrombus formation with the second-generation Amulet device was rare and occurred
      at a rate similar to that of the previous device. Importantly, no patient
      experienced a device-related thromboembolic event during follow-up. Larger real
      life studies are required to confirm the safety profile of this increasingly used
      device.

PMID- 30301673
TI  - Influence of Blood Count, Cardiovascular Risks, Inherited Thrombophilia, and JAK2
      V617F Burden Allele on Type of Thrombosis in Patients With Philadelphia
      Chromosome Negative Myeloproliferative Neoplasms.
AB  - INTRODUCTION: Thrombosis is the most common complication in Philadelphia
      chromosome negative (Ph-) myeloproliferative neoplasms patients. PATIENTS AND
      METHODS: In a cohort of 258 Ph- myeloproliferative neoplasm patients, the
      difference between patients with and without thrombosis was analyzed according to
      genetic thrombophilia factors, JAK2 V617F status and burden allele, blood count,
      cardiovascular risk factors and age. Patients were also divided in polycythemia
      vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)
      subgroups as well as by the type of thrombosis. RESULTS: Analysis of
      cardiovascular risk factors regarding arterial thrombosis showed that PV patients
      with thrombosis had higher incidence of diabetes (P = .030), ET patients more
      often had hypertension (P = .003) and hyperlipidemia (P = .005), while PMF
      patients had hyperlipidemia (P = .046) and at least one cardiovascular risk
      factor (P = .044). Moreover, leukocytes > 18 * 109/L and V617F burden allele >
      25.7% were statistically significantly different in PV patients (P = .019 and
      borderline significant at P = .055, respectively), while in ET patients
      leukocytes > 9.2 * 109/L (P < .001) and age at diagnosis of > 55 years were
      statistically significantly different (P = .002). PMF patients with V617F burden
      allele <= 34.8% were more prone to thrombosis (P = .032). When comparing patients
      with and without venous thrombosis, cutoff value of V617F burden allele > 90.4%
      was significant for PV patients with thrombosis (P = .036), as was > 56.7% for
      PMF patients with thrombosis (P = .046). Platelets <= 536 * 109/L and age at
      diagnosis > 54 years showed statistically significant difference for ET patients
      with thrombosis (P = .015 and P = .041, respectively). CONCLUSION: On the basis
      of our results, a new scoring system for thrombosis risk in PV could be made,
      while PMF prognostic model may be expanded for better recognition of potential
      thrombotic risk factors.

PMID- 30301674
TI  - Novel tacrine-pyridinium hybrid reactivators of organophosphorus-inhibited
      acetylcholinesterase: Synthesis, molecular docking, and in vitro reactivation
      study.
AB  - First-line medical treatment against nerve agents consists of co-administration
      of anticholinergic agents and oxime reactivators, which reactivate inhibited
      AChE. Pralidoxime, a commonly used oxime reactivator, is effective against some
      nerve agents but not against others; thus, new oxime reactivators are needed.
      Novel tacrine-pyridinium hybrid reactivators in which 4-pyridinealdoxime
      derivatives are connected to tacrine moieties by linear carbon chains of
      different lengths (C2-C7) were prepared (Scheme 1, 5a-f). Their binding
      affinities to electric eel AChE were tested because oximes can inhibit free AChE,
      and the highest AChE activity (95%, 92%, and 90%) was observed at 1 MUM
      concentrations of the oximes (5a, 5b, and 5c, respectively). Based on their
      inhibitory affinities towards free AChE, 1 MUM concentrations of the oxime
      derivatives (5) were used to examine reactivation of paraoxon-inhibited AChE.
      Reactivation ability increased as the carbon linker chains lengthened (n = 2-5),
      and 5c and 5d showed remarkable reactivation ability (41%) compared to that of 2
      PAM (16%) and HI-6 (4%) against paraoxon-inhibited electric eel AChE at 1 MUM
      concentrations. Molecular docking simulation showed that the most stable binding
      free energy was observed in 5c at 73.79 kcal?mol-1, and the binding mode of 5c is
      acceptable for the oxygen atom of oximate to attack the phosphorus atom of
      paraoxon and reactivate paraoxon-inhibited eel AChE model structure.

PMID- 30301675
TI  - Identification of inhibitors of the E. coli chaperone SurA using in silico and in
      vitro techniques.
AB  - SurA is a gram-negative, periplasmic chaperone protein involved in the proper
      folding of outer membrane porins (OMPs), which protect bacteria against toxins in
      the extracellular environment by selectively regulating the passage of nutrients
      into the cell. Previous studies demonstrated that deletion of SurA renders
      bacteria more sensitive to toxins that compromise the integrity of the outer
      membrane. Inhibitors of SurA will perturb the folding of OMPs, leading to
      disruption of the outer membrane barrier and making the cell more vulnerable to
      toxic insults. The discovery of novel SurA inhibitors is therefore of great
      importance for developing alternative strategies to overcome antibiotic
      resistance. Our laboratory has screened over 10,000,000 compoundsin silicoby
      computationally docking these compounds onto the crystal structure of SurA.
      Through this screen and a screen of fragment compounds (molecular weight less
      than 250 g/mol), we found twelve commercially readily available candidate
      compounds that bind to the putative client binding site of SurA. We confirmed
      binding to SurA by developing and employing a competitive fluorescence anisotropy
      based binding assay. Our results show that one of these compounds, Fmoc-beta-(2
      quinolyl)-d-alanine, binds the client binding site with high micromolar affinity.
      Using this compound as a lead, we also discovered that Fmoc-l-tryptophan and Fmoc
      l-phenylalanine, but not Fmoc-l-tyrosine, bind SurA with similar micromolar
      affinity. To our knowledge, this is the first report of a competitive
      fluorescence anisotropy assay developed for the identification of inhibitors of
      the chaperone SurA, and the identification of three small molecules that bind
      SurA at its client binding site.

PMID- 30301676
TI  - Discovery of a potent orally bioavailable retinoic acid receptor-related orphan
      receptor-gamma-t (RORgammat) inhibitor, S18-000003.
AB  - The retinoic acid receptor-related orphan receptor-gamma-t (RORgammat) is the
      master transcription factor responsible for regulating the development and
      function of T-helper 17 (Th17) cells, which are related to the pathology of
      several autoimmune disorders. Therefore, RORgammat is an attractive drug target
      for such Th17-mediated autoimmune diseases. A structure-activity relationship
      (SAR) study of lead compound 1 yielded a novel series of RORgammat inhibitors,
      represented by compound 6. Detailed SAR optimization, informed by X-ray cocrystal
      structure analysis, led to the discovery of a potent orally bioavailable
      RORgammat inhibitor 25, which inhibited IL-17 production in the skin of IL-23
      treated mice by oral administration.

PMID- 30301677
TI  - Preventative Health and Risk Behaviors Among Adolescent Girls With and Without
      Family Histories of Breast Cancer.
AB  - PURPOSE: To compare health behaviors (smoking, alcohol use, fruit and vegetable
      intake, and exercise frequency) and breast self-exam (BSE) between girls with
      breast cancer family history (BCFH+) and without (BCFH-) and assess associates of
      behaviors across all girls. METHODS: A total of 208 BCFH+ girls (11-19years old),
      with first- or second-degree relatives with breast cancer or a mother with a
      BRCA1/2 mutation, and 112 BCFH- peers reported their health behaviors, beliefs,
      and psychosocial function. RESULTS: Despite higher BCFH+ girls' greater perceived
      breast cancer risk, there were no differences between BCFH+ and BCFH- girls on
      diet, exercise, alcohol initiation, or BSE. BCFH+ girls were slightly more likely
      to report trying cigarettes (11% vs. 5%, p = .04). In multivariable models with
      all girls, categorical associations with behaviors included the following:
      developmental and demographic factors with smoking, alcohol, diet, and exercise;
      family breast cancer history and experience with smoking, alcohol, and diet;
      psychosocial factors with smoking; girls perceptions of cancer controllability
      and mother support for health behaviors with alcohol, diet, exercise, and BSE;
      and mother behaviors with diet. CONCLUSIONS: Adolescent girls from BCFH+ families
      reported similar health behaviors to BCFH- peers, signaling that they are not
      translating their higher perceived risk into cancer controlbehaviors. Both
      uncontrollable (i.e., breast cancer experiences) and modifiable factors relate to
      health behaviors and warrant further investigation. Results indicate that
      interventions with teens and parents that target modifiable variables such as
      controllability perceptions, maternal modeling, and communication may relate to
      better health behaviors and reduced future breast cancer risk.

PMID- 30301678
TI  - Suicide mortality trends in Spain, 1980-2016.
AB  - OBJECTIVES: To analyse changes in suicide mortality trends in Spain between 1980
      2016 using joinpoint regression models. METHODS: Mortality data were obtained
      from the INE. For each gender, age-group-specific and standardised (overall and
      truncated) rates (ASR) were calculated by the direct method (using the European
      standard population). The joinpoint analysis was used to identify the best
      fitting points where a statistically significant change in the trend occurred.
      RESULTS: Age adjusted mortality rates due to suicide in men was 9.8/100,000 males
      in 1980 and 11.8 in 2016, with an average annual increase of .8%. In women, the
      rates increased by 1.0% per year from 2.7 women per 100,000 in 1980 to 3.7 in
      2016. The joinpoint analysis identified three turning points in the rates for
      both men (1986, 2000 and 2010) and women (1986, 2004 and 2010), which identify
      changes in the trend. In the period 2010-2016 the rates increase in women while
      in men the rates remain stable. CONCLUSIONS: Our work shows a marked increase in
      mortality by suicide in Spanish women (2010-2016) while in men the rates remain
      stable. Little is known about the determinants of the increase and, therefore,
      more studies are needed.

PMID- 30301679
TI  - Advancing the Science of Healthcare Service Delivery: The NHLBI Corporate
      Healthcare Leaders' Panel.
AB  - There is a growing gap between available science and evidence and the ability of
      service providers to deliver high-quality care in a cost-effective way to the
      entire population. We believe that the chasm between knowledge and action is due
      to a lack of concerted effort among all organizations that deliver health care
      services across the life span of patients. Broad participation is needed and
      necessitates a far more explicit and concerted public-private partnership focused
      on large-scale transformation. In this context, the National Heart, Lung, and
      Blood Institute convened a panel made up of leaders of corporate health care
      entities, including academic health centers, and government agency
      representatives to inform contemporary strategic partnerships with health care
      companies. This article provides insights from the meeting on how to execute a
      transformative innovation research agenda that will foster improvements in health
      care service delivery by leveraging the translation of biomedical research
      evidence in real-world settings.

PMID- 30301680
TI  - Global Atlas of Cardiovascular Disease 2000-2016: The Path to Prevention and
      Control.

PMID- 30301681
TI  - Obesity, dynapenia and high cardiovascular risk co-exist in post-liver transplant
      setting: results of a cross-sectional study.
AB  - BACKGROUND: Cardiovascular disease is a major cause of death in post-liver
      transplantation (LT). The aim of this study was to evaluate LT patients as to the
      carotid intima-media thickness (CIMT) and its association with nutritional
      status, dietary intake, metabolic profile and cardiovascular risk factors.
      METHODS: In this cross-sectional study, adult patients with more than 12 months
      of post-transplant follow-up underwent clinical, laboratory, functional and
      nutritional evaluation by 3-day-diet-record, anthropometry and dynamometry. CIMT
      was evaluated by Doppler ultrasonography. RESULTS: Sixty-nine post-LT patients
      [males 61%, median of age 59 (51-64) years were included; median time post-liver
      transplantation 2.8 (1.4-6.3) years]. High prevalence of malnutrition was found
      (45% of arm muscle area < p15 and 71% of handgrip strength < p30). Excess weight
      was present in 72% of patients, body mass index >= 30 kg/m2 in 35% and metabolic
      syndrome in 51%. Abnormal CIMT was found in 54% of the sample. Patients with
      abnormal CIMT presented higher cardiovascular risk Score, LDL cholesterol, higher
      prevalence of high-sensitive C-reactive protein >= 1 mg/L and higher intake of
      saturated and trans fatty acids (P < 0.05 for all). CONCLUSIONS: Abnormal IMT was
      commonly found in LT patients presenting at the same time with overweight and
      dynapemia. These results were associated with higher LDL-cholesterol levels, high
      sensitive C-reactive protein >= 1 mg/L and higher intake of saturated and trans
      fatty acids. Preventive measures, including dietary advice, are required for all
      post-liver transplantation patients to minimize cardiovascular risk.

PMID- 30301682
TI  - Comparing algorithms for composite measures of intra-disease multiple medication
      adherence: The case of diabetes.
AB  - BACKGROUND: Adherence to multiple medications (i.e., separate dosage forms)
      intended for a disease can be measured by different single estimators, termed as
      composite estimators of intra-disease multiple medication adherence: 80% days
      covered (a) by at least one medication ("at least one"); (b) by both medications
      ("both"); (c) by each medication measured separately ("all"); and (d) computing
      an average of the individual medication adherence estimates ("average").
      OBJECTIVES: (a) Assess different composite adherence estimators regarding their
      ability to predict healthcare utilization; (b) compare and contrast composite
      estimators. METHODS: Using MarketScan 2002-2003 data, 6043 nonelderly patients
      who filled separate prescriptions of sulfonylurea [SU] and thiazolidinedione
      [TZD] were identified. Adherence was measured by the proportion of days covered
      (PDC) over periods of 90 days, 30 days, and cumulatively over such periods. Cox
      proportional hazards models analyzed all-cause and diabetes-related emergency
      room (ER) visits as the outcome variables. RESULTS: All composite measures
      predicted hazards of all-cause or diabetes ER visits (P < 0.001) and each measure
      showed statistically significant discriminatory power (concordance statistics
      from 0.55 to 0.58). Cox regression was performed multiple times in which
      composite estimators measured on a continuous scale (e.g., 'average') were
      dichotomized using several cut-points. In the majority of cases (<=3 out of 8
      times in analyses of ER outcomes), optimal results did not occur when the
      dichotomization cut-point was set at 80%. CONCLUSIONS: Each composite estimator
      showed the fundamental quality of a good measure. Although 'average' and 'all'
      approaches offer ease of measurement, there was no clear trend in superiority of
      one measure over the others. Clinical and practical considerations should dictate
      the choice of measure.

PMID- 30301683
TI  - Clinical and economic considerations based on persistency with a novel insulin
      delivery device versus conventional insulin delivery in patients with type 2
      diabetes: A retrospective analysis.
AB  - OBJECTIVE: Insulin is one of the most efficacious treatments for hyperglycemia;
      however, adherence to insulin therapy is poor, impacting its efficacy. Thus, the
      objectives of this study were to determine if persistent use of a new insulin
      delivery option, V-Go, improved clinical outcomes and secondly compare clinical
      and economic outcomes between persistent use of V-Go and conventional insulin
      delivery (CID). METHODS: A retrospective review of an outpatient clinic's records
      was performed. Patients initiating V-Go with documented persistent use of V-Go or
      resumed persistent use of CID after short-term V-Go use were included (>=5 months
      of persistency). Baseline data and a total of two post-V-Go or CID initiation
      visits were examined for clinical and economic outcomes. Cost-effectiveness of
      each therapy was calculated by dividing the mean cost difference (baseline to
      office visit 2) by the mean change in A1c (baseline to office visit 2). RESULTS:
      V-Go persistent patients had a significant decrease in A1c (-1.42; p < 0.001).
      Between baseline and office visit two, they required less insulin units/day and
      units/kg and had significantly lower A1c, insulin units/day, insulin units/kg,
      and 30-day insulin costs than CID patients. V-Go persistent patients had a lower
      incremental cost by $695.61 per 1% change in A1c compared to CID persistent
      patients. CONCLUSIONS: Utilization of a new insulin delivery option resulted in
      improved clinical outcomes compared to CID and was more cost-effective.
      Clinicians and health plans should consider the use of new insulin delivery
      options for the management of patients with diabetes on insulin therapy to
      promote persistence.

PMID- 30301684
TI  - Comparison of outcomes in women and men following carotid interventions in the
      Washington state's Vascular Interventional Surgical Care and Outcomes Assessment
      Program.
AB  - BACKGROUND: The benefit for carotid endarterectomy (CEA) to prevent a potential
      stroke has been shown to be less beneficial for women compared with men and the
      risk of carotid stenting (CAS) is higher in women than men. We hypothesized that
      a community-based Washington state registry data would also reveal increased
      morbidity and mortality for women undergoing carotid interventions. METHODS:
      Deidentified data for CEA and CAS between 2010 and 2015 were obtained from 19
      hospitals participating in the Washington State Vascular-Interventional Surgical
      Care and Outcomes Assessment Program. Data analysis compared in-hospital
      composite outcome of stroke and mortality from CEA and CAS between women and men.
      RESULTS: Over the study period, 3704 individuals underwent CEA (n = 2759; 49.5%
      symptomatic) and CAS (n = 945; 60.9% symptomatic). Women accounted for 39.5% of
      the cohort. Women were slightly younger than men (70.0 +/- 10.2 vs 71.0 +/- 9.6
      years respectively; P < .01), less likely to be smokers (70.1% vs 75.6%; P <
      .01), and less likely to have a diagnosis of coronary artery disease (32.9% vs
      46.5%; P < .01). Fewer women underwent CEA for symptomatic carotid disease (46.1%
      vs 51.8%; P < .01). There were no statistically significant differences in the
      postoperative in-hospital stroke and mortality among women and men undergoing CEA
      (asymptomatic, 0.8% vs 1.4% [P = .36]; symptomatic, 1.8% vs 2.2% [P = .58]) and
      CAS (asymptomatic, 1.4% vs 2.2% [P = .56]; symptomatic, 4.6% vs 2.5% [P = .18]).
      Hospital duration of stay and discharge disposition were similar for women and
      men. A subanalysis of the octogenarian cohort undergoing CAS demonstrated a
      substantial increase in-hospital stroke and mortality among women and men (11.6%
      [CAS] vs 2.2% [CEA]; P = .024). CONCLUSIONS: In the Washington state Vascular
      Interventional Surgical Care and Outcomes Assessment Program registry, hospital
      composite outcome of stroke and mortality following carotid interventions from
      2010 to 2015 were noted to be similar for women and men. The notable exception to
      this finding was observed in subcohort of women undergoing CAS for symptomatic
      carotid disease at age 80 years or older. These findings should be taken into
      account when risk stratifying patients for carotid interventions.

PMID- 30301685
TI  - Comparison of one-stage and two-stage upper arm brachiobasilic arteriovenous
      fistula in the Vascular Quality Initiative.
AB  - OBJECTIVE: An upper arm brachiobasilic arteriovenous fistula (BBAVF) is a
      reliable autogenous hemodialysis access created with a one-stage or two-stage
      technique. Although both techniques are variably used, the optimal approach is
      uncertain. In this study, we compared the outcomes of one-stage and two-stage
      BBAVF procedures. METHODS: We identified 2648 patients who had received BBAVFs
      within the Vascular Quality Initiative data set (2010-2016) and compared those
      created using the one-stage and two-stage technique. The primary outcome measures
      were primary and secondary patency rates at 12 months. Other outcomes assessed
      were wound infection, steal, and swelling at 3 months. The log-rank test was used
      to evaluate patency by Kaplan-Meier analysis. Cox proportional hazards models
      were used to examine the adjusted association between surgical technique and
      outcomes. RESULTS: There were 1234 (47%) one-stage and 1414 (53%) two-stage
      BBAVFs in the study cohort, including 1848 (70%) patients who were on dialysis at
      the time of surgery and 1795 (68%) patients with a history of previous access.
      Patients who underwent a one-stage BBAVF were more likely to be male (54% vs 45%;
      P < .001), to be white (60% vs 41%; P < .001), and to have a history of coronary
      artery disease (22% vs 17%; P = .001). Patients undergoing one-stage BBAVFs have
      larger vein diameters (4.1 vs 3.4 mm; P < .001) and have the procedure in an
      inpatient setting (21% vs 13%; P < .001) compared with patients undergoing a two
      stage procedure. The 12-month primary patency rate was higher for the one-stage
      BBAVF (49.1% vs 40.4%; P = .005), although the secondary patency rate was
      comparable (80.0% vs 77.9%; P = .54). Postoperative bleeding (4% vs 1.5%; P <
      .001), wound infection (1.01% vs 0.4%; P = .047), and arm swelling (2.1 % vs
      0.8%; P = .006) were higher for one-stage BBAVFs. In multivariable analysis,
      although loss of primary patency at 12 months (adjusted hazard ratio [aHR], 1.12;
      95% confidence interval [CI], 0.97-1.30; P = .12) and 3-month wound infection
      (aHR, 0.42; 95% CI, 0.14-1.25, P = .12) were similar between the two approaches,
      the risk of 3-month arm swelling was significantly lower for two-stage BBAVFs
      (aHR, 0.35; 95% CI, 0.16-0.77; P = .009). CONCLUSIONS: Whereas surgeons were more
      likely to perform a two-stage BBAVF in patients with a history of previously
      failed access and smaller basilic vein, our data show no difference in primary or
      secondary patency of one-stage and two-stage BBAVFs at 12 months.

PMID- 30301686
TI  - Patient satisfaction and chronic illness are predictors of postendovascular
      aneurysm repair surveillance compliance.
AB  - OBJECTIVE: Although lifelong surveillance is recommended by the Society for
      Vascular Surgery for patients undergoing endovascular aneurysm repair (EVAR)
      reported that compliance with long-term follow-up has been poor. We sought to
      identify factors that predict compliance with EVAR surveillance through analysis
      of patient variables and post-EVAR questionnaire results. METHODS: We analyzed 28
      patient variables gathered from our computerized registry, patient charts, and
      phone questionnaires of patients who underwent EVAR between January 1, 2010, and
      December 31, 2014. These factors included patient demographics, education,
      postoperative complications, satisfaction with vascular surgery care,
      transportation mode, distance to our medical center, and living situation.
      Compliance was defined as a patient who underwent the most recent recommended
      follow-up surveillance study within the prescribed timeframe. Post-EVAR
      surveillance protocol consisted of office evaluation and duplex ultrasound
      examination performed in our accredited noninvasive vascular laboratory at 1
      week, 6 months, then annually. Computed tomography angiography was obtained only
      if duplex ultrasound examination suggested endoleak, sac enlargement of more than
      5 mm, or a failing limb. RESULTS: Of 144 patients who underwent EVAR during this
      time period, 89 patients (62%) were compliant with the most recent recommended
      follow-up study. One hundred two patients completed the questionnaire or their
      families did if patients died or were incapacitated. Of those, 80 were compliant
      with follow-up and 22 were not. Based on the questionnaires of these 102
      patients, estimated compliance at 3 years after EVAR was 69.6 +/- 6.0% based on
      Kaplan-Meier analysis. In the compliant vs noncompliant groups, the estimated 3
      year survival rate was 93.2 +/- 3.4% vs 52.4 +/- 12.7%, respectively (P < .001),
      and the estimated 5-year survival rate was 83.1 +/- 6.4% vs 34.4 +/- 13.4%,
      respectively (P < .001), respectively. However, none of the mortalities observed
      in the noncompliant group were aneurysm related. Adverse neurologic events after
      EVAR demonstrated a trend predicting noncompliance after 5 years based on
      multivariate Cox regression analysis (hazard ratio [HR], 2.57; 95% confidence
      interval [CI], 0.95-6.90; P = .062). Patient dissatisfaction with their vascular
      surgeon and hospital care predicted noncompliance with recommended postoperative
      surveillance (HR, 5.0; 95% CI, 1.52-16.7; P = .008). College education or higher
      was associated with compliance (HR, 0.28; 95% CI, 0.06-1.23; P = .092). No other
      variables, including postoperative complications or distance from the hospital,
      predicted follow-up noncompliance. CONCLUSIONS: Patient satisfaction with their
      vascular surgeon and hospital experience predicted compliance with post-EVAR
      surveillance regardless of postoperative complications. Noncompliant patients had
      decreased survival, but mortality and surveillance noncompliance were likely due
      to disabling chronic disease.

PMID- 30301687
TI  - Aortic neck dilation is not associated with adverse outcomes after fenestrated
      endovascular aneurysm repair: Midterm results from an investigational device
      exemption clinical trial.
AB  - OBJECTIVE: Long-term outcomes after endovascular aneurysm repair (EVAR) are
      threatened by aortic neck dilation (AND), graft migration, and subsequent
      endoleak development. The aim of this study was to determine the rate of AND and
      the occurrence of endoleaks after fenestrated EVAR of juxtarenal aneurysms with
      physician-modified endovascular grafts (PMEGs). METHODS: The study included 77
      patients presenting with asymptomatic and ruptured juxtarenal abdominal aortic
      aneurysms treated with PMEGs who received radiologic follow-up. Analysis of
      computed tomography images took place on a three-dimensional workstation
      (TeraRecon, San Mateo, Calif). Aortic neck diameter was measured before and after
      EVAR at the lowest patent renal artery outer wall to outer wall. Significant AND
      was defined as >3-mm increase between baseline and follow-up, and sac regression
      >5 mm was considered significant. The patient's 1-month initial postoperative
      computed tomography measurement was considered baseline. The rate of AND was
      measured by comparing the baseline measurement with measurements at 6 months, 12
      months, and annually thereafter up to 4 years. RESULTS: In this cohort of
      patients, 75% were men with a mean age of 74 +/- 7.9 years. Median preoperative
      aneurysm size was 62 (57-73) mm, and median follow-up was 12 (3.5-30) months.
      Mean endograft oversizing was 17% +/- 12.5%, and mean seal zone length was 41 +/-
      11 mm. At 1-year follow-up, the median aortic neck increase was 1.7 (0-3) mm.
      Maximum aneurysm size decreased dramatically during the first postoperative year,
      with significant sac regression in 65% of the patients. Aortic neck diameter at 1
      year did correlate positively with the percentage of device oversizing. No other
      correlations were found. During the 4-year follow-up, there were no cases of type
      IA endoleaks. CONCLUSIONS: AND does not influence outcome after endovascular
      repair of juxtarenal aneurysms using PMEGs. These midterm results support the
      applicability of PMEGs in juxtarenal aneurysm repair.

PMID- 30301688
TI  - The role of ascending aortic size in outcomes of patients with uncomplicated
      acute type B aortic dissection.
AB  - OBJECTIVE: Recent studies demonstrate that uncomplicated acute type B aortic
      dissection (uATBAD) patients with enlarged descending thoracic aortic diameters
      are at high risk for development of complications. This study aimed to determine
      the association of maximum ascending aortic diameter and area and outcomes in
      patients with uATBAD. METHODS: All patients admitted with uATBAD from June 2000
      to January 2015 were reviewed, and those with available imaging were included.
      All measurements were obtained by a specialized cardiovascular radiologist,
      including the maximum ascending aortic diameter and area. Outcomes, including the
      need for intervention and mortality, were tracked over time. Data were analyzed
      by stratified Kaplan-Meier and multiple Cox regression analyses using SAS 9.4
      software (SAS Institute, Cary, NC). RESULTS: During the study period, 298
      patients with uATBAD were admitted, with 238 having available computed tomography
      and 131 having computed tomography angiography imaging and adequate follow-up
      available for analysis. The cohort had an average age of 60.96 +/- 13.4 years
      (60% male, 53% white). Ascending aortic area >12.1 cm2 and ascending aortic
      diameter >40.8 mm were associated with subsequent arch and proximal progression
      necessitating open ascending aortic repair (P < .027 and P < .033, respectively).
      Ascending diameter >40.8 mm predicted lower intervention-free survival (P = .01).
      However, it failed to predict overall survival (P = .12). Ascending aortic area
      >12.1 cm2 predicted lower intervention-free survival (P = .005). However, this
      was not predictive of mortality (P = .08). Maximum aortic diameter along the
      length of the aorta >44 mm persisted as a risk factor for mortality (P < .001).
      Neither maximum ascending aortic diameter >40.8 mm (hazard ratio [HR], 1.09; 95%
      confidence interval [CI], 0.42-2.83; P = .85) nor area >12.1 cm2 (HR, 0.992; 95%
      CI, 0.38-2.61; P = .99) significantly predicted mortality when controlling for
      maximum aortic diameter along the length of the aorta >44 mm (HR, 7.34; 95% CI,
      2.3-23.41; P < .001), diabetes mellitus (HR, 6.4; 95% CI, 2.17-18.93; P < .001),
      age (HR, 1.06/y; 95% CI, 1.03-1.10; P < .001), history of stroke (HR, 5.03; 95%
      CI, 1.52-16.63; P = .008), and syncope on admission (HR, 21.11; 95% CI, 2.3
      193.84; P = .007). Ascending aortic diameter >40.8 mm (HR, 2.01; 95% CI, 1.03
      3.95; P = .04) and maximum ascending aortic area >12.1 cm2 (HR, 1.988; 95% CI,
      1.02-3.87; P = .04) on admission persisted as predictors of decreased
      intervention-free survival after controlling for maximum aortic diameter along
      the length of the aorta >44 mm (HR, 3.142; 95% CI, 1.47-6.83; P < .004), syncope
      on admission (HR, 26.3; 95% CI, 2.81-246; P < .004), and pleural effusion on
      admission (HR, 3.02; 95% CI, 1.58-5.77; P < .001). CONCLUSIONS: uATBAD patients
      with ascending aortic area >12.1 cm2 or maximum ascending aortic diameter >40.8
      mm are at high risk for development of subsequent arch and proximal progression
      and may require closer follow-up or earlier intervention. Ascending aortic size
      (diameter and area) is predictive of decreased intervention-free survival in
      patients with uATBAD.

PMID- 30301689
TI  - In-hospital versus postdischarge major adverse events within 30 days following
      lower extremity revascularization.
AB  - OBJECTIVE: Studies using hospital discharge data likely underestimate
      postoperative morbidity and mortality after lower extremity revascularization
      because they fail to capture postdischarge events. However, the degree of
      underestimation and the timing of postdischarge complications are not well
      characterized. METHODS: We used the American College of Surgeons National
      Surgical Quality Improvement Program procedure-targeted vascular databases from
      2011 to 2015 to tabulate 30-day adverse events (in hospital and after discharge)
      for lower extremity bypass (LEB) and percutaneous vascular interventions (PVIs)
      performed for claudication and chronic limb-threatening ischemia (CLTI). RESULTS:
      A total of 14,125 patients underwent lower extremity revascularization, 8909
      patients (63%) with LEB and 5216 (37%) with PVI. For CLTI, total 30-day mortality
      was similar between PVI and LEB (2.3% vs 2.1%; P = .61), but in-hospital deaths
      only accounted for 43% of PVI mortality and only 65% of LEB mortality (P <=
      .001). Major adverse cardiac events occurred in 2.9% of PVI patients and 4.6% of
      LEB patients (P < .001), with postdischarge events accounting for 37% of PVI
      events and 18% of LEB (P <= .001). Although the 30-day reoperation rates were 14%
      for PVI and 18% for LEB (P < .001), almost one-half occurred after discharge (PVI
      46% vs LEB 44%; P = .55). Any postoperative major adverse events (MAEs) occurred
      in 22% of patients after PVI and 31% after LEB, with more than one-half occurring
      after discharge (PVI 56% vs LEB 53%; P = .17). For claudicants, total 30-day
      mortality was 0.4% for PVI and 0.7% for LEB (P = .32), with the vast majority of
      events occurring after discharge (PVI 90% vs LEB 50%; P = .049). The 30-day
      reoperation rates were 5.2% for PVI and 8.0% for LEB (P < .001), with more than
      one-half occurring after discharge (PVI 63% vs LEB 53%; P = .09). Any MAEs
      occurred in 7.0% of patients after PVI and 17% after bypass, with the majority
      occurring after discharge (PVI 65% vs LEB 63%; P = .66). CONCLUSIONS: Most MAEs
      occur less frequently after PVI than LEB. However, a significant number of major
      of adverse events after lower extremity revascularization occur after leaving the
      hospital, especially after PVI, which may overestimate its benefits compared with
      LEB if only in-hospital data are evaluated. These data demonstrate the importance
      of reporting 30-day rather than in-hospital outcomes when evaluating
      postoperative adverse events.

PMID- 30301690
TI  - Outcomes associated with a transcarotid artery revascularization-centered
      protocol in high-risk carotid revascularizations using the ENROUTE
      neuroprotection system.
AB  - OBJECTIVE: This investigation describes the perioperative and early follow-up
      results associated with transcarotid artery revascularization (TCAR) in patients
      not participating in the Safety and Efficacy Study for Reverse Flow Used During
      Carotid Artery Stenting Procedure II (ROADSTER-2) registry using the ENROUTE
      neuroprotection system (ENPS; Silk Road Medical, Sunnyvale, Calif). METHODS: A
      retrospective review was performed capturing all TCAR/ENPS procedures in patients
      deemed to be at high risk for complications after traditional carotid
      endarterectomy. All patients enrolled in the ROADSTER-2 registry were excluded,
      leaving only those treated outside trial regulations for analysis. Preoperative
      demographics, intraoperative variables, and perioperative and follow-up outcomes
      were abstracted and reported herein. RESULTS: From December 2015 to January 2018,
      there were 75 carotid arteries treated at our institution. All interventions were
      performed on carotid arteries that were symptomatic with >=50% stenosis (46.7%)
      or asymptomatic with >=80% stenosis (53.3%) by duplex ultrasound and computed
      tomography angiography. Technical success in our series was 97.3% (73/75), with
      treatment failures attributed to one case of common carotid artery dissection and
      another secondary to stent maldeployment in the external carotid artery.
      Perioperative (30-day) ipsilateral stroke rate was 2.7% (n = 2), myocardial
      infarction incidence was 0%, and mortality rate was 2.7% (n = 2). We did not
      observe any cranial nerve injuries. After a mean follow-up of 8.0 +/- 6.7 months,
      no carotid stents required reintervention. However, we noted one instance of
      minor (<50%) in-stent stenosis and one asymptomatic stent thrombosis. One
      additional ipsilateral stroke was observed on follow-up, probably from a cardiac
      source. CONCLUSIONS: We report that dynamic reverse-flow TCAR using the ENPS
      continues to be safe, feasible, and efficacious with minimal risks of
      postoperative stroke, myocardial infarction, and mortality outside of ROADSTER-2
      regulations.

PMID- 30301691
TI  - Burnout, depression, perceived stress, and self-efficacy in vascular surgery
      trainees.
AB  - OBJECTIVE: Burnout is a work-related syndrome involving emotional exhaustion,
      depersonalization, and a sense of reduced personal accomplishment that has become
      prevalent in all levels of medical training. We sought to understand factors
      associated with burnout identified in vascular surgery trainees. METHODS: An
      anonymous electronic survey consisting of demographic and programmatic
      information as well as validated scales for burnout, depression, perceived
      stress, self-efficacy, and social support was given to all vascular surgery
      trainees in the United States. Univariate and multivariate analyses were used to
      compare responses. Residents were grouped into quartiles based on burnout level,
      and predictors of burnout were determined. RESULTS: Of the 514 invitations sent,
      177 (34%) respondents completed the survey. Trainees in the highest quartile of
      burnout were more likely to have moderate to severe depression (40% vs 4%; P <
      .01), higher perceived stress score (odds ratio [OR], 1.3; P < .01), lower social
      support (OR, 0.89; P < .01), and lower self-efficacy (OR, 0.76; P < .01), and
      they were less likely to reconsider vascular surgery as a career if given the
      chance to do it over (chi2 = 20; P < .01). Trainees without a self-identified
      mentor were significantly more likely to report burnout (chi2 = 15; P < .01). In
      addition, trainees who reported more frequent 80-hour work infractions each month
      (3.6 vs 2.3; P < .01) and those without access to programmatic social events
      (chi2 = 11; P < .01) had higher levels of burnout. In contrast, trainees with the
      lowest quartile of burnout scores reported lower depression (OR, 0.43; P < .01),
      lower stress (OR, 0.63; P < .01), more social support (OR, 0.1.2; P < .01),
      higher self-efficacy (OR, 1.2; P < .01), and fewer work week violations each
      month (2.3 vs 2.9; P = .04). Lower burnout scores were associated with program
      mentorship (chi2 = 7.3; P < .01), program-sponsored social events (chi2 = 8.7; P
      < .01), and being more likely to choose vascular surgery again if given the
      chance (chi2 = 6.3; P < .01). Highest burnout scores did not correlate with sex
      (chi2 < .01; P = 1), age (32 years vs 32 years; P = .65), marital status (chi2 <
      .01; P = 1), proximity to family (OR, 1.2; P = .26), alcohol consumption (chi2 =
      0.23; P = .63), postgraduate year (OR, 1.1; P = .47), number of prior program
      graduates (OR, 0.95; P = .73), use of physician extenders in the program (OR,
      0.93; P = .74), or total debt (OR, 1.0; P = .63). Similarly, there were no
      significant associations with these variables among trainees with the lowest
      quartile of burnout scores. On multivariate analysis, higher depression (OR, 1.6;
      P < .01) and higher perceived stress (OR, 1.2; P < .01) were associated with
      higher burnout scores, and lower burnout scores were associated with lower
      perceived stress (OR, 0.67; P < .01). CONCLUSIONS: Burnout in vascular surgery
      trainees is associated with higher levels of depression and perceived stress and
      lower levels of social support and self-efficacy. The addition of programmatic
      social events, limiting 80-hour work week violations, and addition of formal
      mentoring programs may decrease levels of burnout.

PMID- 30301692
TI  - Endovascular aneurysm repair in patients over 75 is associated with excellent 5
      year survival, which suggests benefit from expanded screening into this cohort.
AB  - BACKGROUND: Endovascular aneurysm repair (EVAR) has decreased the perioperative
      mortality for patients undergoing abdominal aortic aneurysm repair and has
      increased the rates of elective aneurysm repair in the elderly. However, Medicare
      will not cover abdominal aortic aneurysm screening for beneficiaries over 75
      years of age. Consequently, abdominal aortic aneurysm treatment in this
      population depends on incidental detection. Targeted coverage for screening in
      this population, however, might be beneficial for a subgroup of patients.
      METHODS: To identify a subset of elderly patients who would potentially benefit
      from an expanded screening policy, we reviewed all patients greater than 75 years
      old undergoing elective EVAR in the Vascular Quality Initiative between 2003 and
      2016. We used Cox regression with multivariable fractional polynomials to
      construct a risk model for 5-year survival in elderly patients to identify a
      subpopulation who might benefit the most from screening and performed internal
      validation using the bootstrapping technique. RESULTS: We identified 10,676
      patients greater than 75 years old undergoing elective EVAR. Although
      perioperative mortality varied with age, it was only 2.1% in the oldest group of
      patients (>85 years). Significant predictors included in our final risk model for
      5-year survival in the elderly included age, aortic diameter, hemoglobin, current
      smoking, white race, body mass index, renal function, congestive heart failure,
      statin use, chronic obstructive pulmonary disease, and ejection fraction. The
      risk model produced risk scores ranging from a possible -2 to 33. The mean and
      median risk score were 6.9 and 6.0, respectively, with a right skew. We
      categorized the risk scores into four groups: -2 to 4 points, 5-8 points, 9-13
      points, and more than 13 points, with associated 5-year survivals of 88%, 79%,
      68%, and 49%, respectively. The model showed adequate discrimination and
      calibration, with a C-statistic of 0.69 and a calibration score of 0.99
      (predicted 5-year survival of 0.78 compared with an observed 5-year survival of
      0.77) and a Brier score of 0.15. Internal validation demonstrated an optimism
      corrected C-statistic of 0.69 and a calibration slope of 1.0. CONCLUSIONS:
      Elective EVAR in elderly patients chosen to undergo repair is associated with
      acceptable perioperative mortality. Our risk score can be used to define optimal
      patients for expanded screening into all but the highest risk group based on
      expected postoperative 5-year survival to justify removing this Medicare coverage
      restriction.

PMID- 30301693
TI  - Three-dimensional image fusion is associated with lower radiation exposure and
      shorter time to carotid cannulation during carotid artery stenting.
AB  - OBJECTIVE: Three-dimensional (3D) image fusion is associated with lower radiation
      exposure, contrast agent dose, and operative time during endovascular abdominal
      aortic aneurysm repair. Therefore, we evaluated the impact of this technology on
      carotid artery stenting (CAS). METHODS: We identified consecutive CAS procedures
      from 2009 to 2017 and compared those performed with and without 3D image fusion.
      For image fusion, we created a 3D reconstruction of the aortic arch anatomy based
      on preoperative computed tomography or magnetic resonance angiography that we
      merged with two-dimensional fluoroscopy, allowing 3D image overlay. We compared
      radiation exposure, fluoroscopy time, contrast agent dose, time to common carotid
      artery (CCA) cannulation, time from CCA cannulation to completion angiography,
      and total procedure time in procedures with and without image fusion. We also
      assessed rates of 30-day stroke/death, in-hospital and 30-day stroke, and acute
      kidney injury. We used multivariable linear regression to adjust for patient and
      procedural characteristics and used these models to compute the marginal effects
      of image fusion compared with no image fusion. RESULTS: There were 46 patients
      who underwent CAS with a 3D image fusion system and 70 patients without. Patients
      undergoing CAS with image fusion experienced 31% lower radiation exposure
      compared with the control group (207 +/- 23 mGy vs 300 +/- 26 mGy, respectively;
      P < .01), shorter fluoroscopy time (21 +/- 6 minutes vs 24 +/- 8 minutes; P =
      .02), shorter time to carotid cannulation (21 +/- 9 minutes vs 31 +/- 8 minutes;
      P < .001), and shorter total procedure time (47 +/- 13 minutes vs 54 +/- 18
      minutes; P = .03). There was no difference in contrast material volume, time from
      CCA cannulation to completion angiography, or total in-room time. After
      multivariable adjustment, 3D image fusion remained associated with lower
      radiation dose, shorter fluoroscopy time, and shorter time to carotid cannulation
      (all P < .05). The rate of 30-day stroke/death was 2.7% (three strokes and no
      deaths at 30 days), and the rate of acute kidney injury was 1.8%. CONCLUSIONS:
      CAS with 3D image fusion was associated with lower radiation exposure and shorter
      time to CCA cannulation. These results represent the potential technical
      advantage gained with image fusion and add to the growing body of evidence
      demonstrating its impact on radiation exposure and operative times during complex
      endovascular procedures.

PMID- 30301694
TI  - Identifying the Optimal Candidate for Salvage Lymph Node Dissection for Nodal
      Recurrence of Prostate Cancer: Results from a Large, Multi-institutional
      Analysis.
AB  - BACKGROUND: Salvage lymph node dissection (SLND) represents a possible treatment
      option for prostate cancer patients affected by nodal recurrence after local
      treatment. However, SLND may be associated with intra- and postoperative
      complications, and the oncological benefit may be limited to specific groups of
      patients. OBJECTIVE: To identify the optimal candidates for SLND based on
      preoperative characteristics. DESIGN, SETTING, AND PARTICIPANTS: The study
      included 654 patients who experienced prostate-specific antigen (PSA) rise and
      nodal recurrence after radical prostatectomy (RP) and underwent SLND at nine
      tertiary referral centers. Lymph node recurrence was documented by positron
      emission tomography/computed tomography (PET/CT) scan using either 11C-choline or
      68Ga-labeled prostate-specific membrane antigen ligand. INTERVENTION: SLND.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The study outcome was early
      clinical recurrence (eCR) developed within 1 yr after SLND. Multivariable Cox
      regression analysis was used to develop a predictive model. Multivariable-derived
      coefficients were used to develop a novel risk calculator. Decision-curve
      analysis was used to evaluate the net benefit of the predictive model. RESULTS
      AND LIMITATIONS: Median follow-up was 30 (interquartile range, 16-50) mo among
      patients without clinical recurrence (CR), and 334 patients developed CR after
      SLND. In particular, eCR at 1 yr after SLND was observed in 150 patients, with a
      Kaplan-Meier probability of eCR equal to 25%. The development of eCR was
      significantly associated with an increased risk of cancer-specific mortality at 3
      yr, being 20% versus 1.4% in patients with and without eCR, respectively
      (p<0.0001). At multivariable analysis, Gleason grade group 5 (hazard ratio [HR]:
      2.04; p<0.0001), time from RP to PSA rising (HR: 0.99; p=0.025), hormonal therapy
      administration at PSA rising after RP (HR: 1.47; p=0.0005), retroperitoneal
      uptake at PET/CT scan (HR: 1.24; p=0.038), three or more positive spots at PET/CT
      scan (HR: 1.26; p=0.019), and PSA level at SLND (HR: 1.05; p<0.0001) were
      significant predictors of CR after SLND. The coefficients of the predictive model
      were used to develop a risk calculator for eCR at 1 yr after SLND. The
      discrimination of the model (Harrel'sC index) was 0.75. At decision-curve
      analysis, the net benefit of the model was higher than the "treat-all" option at
      all the threshold probabilities. CONCLUSIONS: We reported the largest available
      series of patients treated with SLND. Roughly 25% of men developed eCR after
      surgery. We developed the first risk stratification tool to identify the optimal
      candidate to SLND based on routinely available preoperative characteristics. This
      tool can be useful to avoid use of SLND in men more likely to progress despite
      any imaging-guided approach. PATIENT SUMMARY: The risk of early recurrence after
      salvage lymph node dissection (SLND) was approximately 25%. In this study, we
      developed a novel tool to predict the risk of early failure after SLND. This tool
      will be useful to identify patients who would benefit the most from SLND from
      other patients who should be spared from surgery.

PMID- 30301695
TI  - Prognostic Implication of the United States Food and Drug Administration-defined
      BCG-unresponsive Disease.
AB  - The category "BCG-unresponsive disease", formulated by experts at the request of
      the United States Food and Drug Administration, denotes a group of patients with
      recurrent non-muscle-invasive bladder cancer for whom continued BCG treatment is
      unlikely to provide benefit. Although quickly adopted for trial design, many of
      the nuances within the definition lack validation. In this study, we evaluated
      the prognostic value of BCG unresponsive designation (i.e. recurrence after
      induction plus at least 1 maintenance course of BCG) by comparing the oncologic
      outcomes of these patients with those recurring after induction BCG alone. We
      confirm that appropriately defined, BCG-unresponsive patients are more likely to
      require salvage radical cystectomy (54.5% vs 17.9%, p=0.002). Moreover, those
      opting for second-line bladder-sparing therapies are less likely to remain free
      of tumor recurrence (23% vs 69.2%, p=0.003). On multivariate analysis, BCG
      unresponsive disease independently predicts inferior high-grade recurrence-free
      survival (hazard ratio [HR]: 6.25, 95% confidence interval [CI]: 2.27-16.67;
      p<0.001) and cystectomy-free survival (HR: 3.85, 95% CI: 1.49-10.0; p=0.006). Our
      data confirm the prognostic implication of the BCG unresponsive definition i.e.
      recurrence of high grade disease after induction and one course of maintenance
      BCG, and support its use in counseling and risk stratification of patients with
      tumor recurrence after BCG. Patient summary: Patients who have BCG-unresponsive
      disease, that is, high-grade non-muscle-invasive bladder cancer recurring after
      BCG induction and maintenance, have a low likelihood to respond to further BCG
      treatment and should consider radical cystectomy or clinical trial enrollment.

PMID- 30301696
TI  - A Prospective Study of the Association between Physical Activity and Risk of
      Prostate Cancer Defined by Clinical Features and TMPRSS2:ERG.
AB  - BACKGROUND: Growing evidence shows that clinical and molecular subtypes of
      prostate cancer (PCa) have specific risk factors. Observational studies suggest
      that physical activity may lower the risk of aggressive PCa. To our knowledge,
      the association between physical activity and PCa defined by TMPRSS2:ERG has not
      been evaluated. OBJECTIVE: To prospectively examine the association between
      physical activity and risk of PCa defined by clinical features and TMPRSS2:ERG.
      DESIGN, SETTING, AND PARTICIPANTS: We studied 49160 men aged 40-75 yr in the
      Health Professionals Follow-up Study from 1986 to 2012. Data was collected at
      baseline and every 2 yr with >90% follow-up. Total and vigorous physical activity
      were measured in metabolic equivalent of task (MET)-h/wk. OUTCOME MEASURES AND
      STATISTICAL ANALYSIS: Advanced PCa was defined as stage T3b, T4, N1, or M1 at
      diagnosis and lethal PCa as distant metastases or death due to disease over
      follow-up. Presence of TMPRSS2:ERG was estimated by immunohistochemistry of ERG
      protein expression. Cox proportional hazards models were used to obtain
      multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for
      incidence of subtype-specific PCa. RESULTS AND LIMITATIONS: During 26 yr of
      follow-up, 6411 developed PCa overall and 888 developed lethal disease. There
      were no significant associations between total physical activity and risk of PCa
      in the overall cohort. In multivariable-adjusted models, men in the highest
      quintile of vigorous activity had a significant 30% lower risk of advanced PCa
      (HR: 0.70, 95% CI: 0.53-0.92) and 25% lower risk of lethal PCa (HR: 0.75, 95% CI:
      0.59-0.94) than men in the lowest quintile of vigorous activity. The association
      was independent of screening history. Vigorous activity was not associated with
      total PCa in the overall cohort but was inversely associated among highly
      screened men (top vs bottom quintile, HR: 0.83, 95% CI: 0.70-0.97). Of all cases,
      945 were assayed for ERG (48% ERG-positive). Men with higher vigorous activity
      had a lower risk of ERG-positive PCa (top vs bottom quintile, HR: 0.71, 95% CI:
      0.52-0.97). There was no significant association with the risk of ERG-negative
      disease (p heterogeneity=0.09). CONCLUSIONS: Our study confirms that vigorous
      physical activity is associated with lower risk of advanced and lethal PCa and
      provides novel evidence for a lower risk of TMPRSS2:ERG-positive disease. PATIENT
      SUMMARY: The identification of modifiable lifestyle factors for prevention of
      clinically important prostate cancer (PCa) is needed. In this report, we compared
      risk of PCa in men with different levels of physical activity. Men with higher
      vigorous activity had a lower risk of developing advanced and lethal PCa and PCa
      with the common TMPRSS2:ERG gene fusion.

PMID- 30301697
TI  - Reply to Francesco Montorsi and Giorgio Gandaglia's Letter to the Editor re:
      Georg Jancke, Firas Aljabery, Sigurdur Gudjonsson, et al. Port-site Metastases
      After Robot-assisted Radical Cystectomy: Is There a Publication Bias? Eur Urol
      2018;73:641-2.

PMID- 30301698
TI  - Focal therapy in localised prostate cancer: Real-world urological perspective
      explored in a cross-sectional European survey.
AB  - INTRODUCTION: The urological community's opinion over focal therapy (FT) for
      prostate cancer (PCa) has never been assessed. Our aim was to investigate the
      current opinion on FT in the European urological community. METHODS: A 25-item
      questionnaire was devised according to the Cherries checklist and distributed
      through SurveyMonkey using a web link from November 2016 to October 2017. After a
      pilot validation (n = 40 urologists), the survey was sent through EAU and 9 other
      national European urological societies mailing list. Twitter was also used.
      RESULTS: We received 484 replies from 51 countries. Almost half (44.8%, n = 217)
      stated FT would represent a step forward, and 52.0% (n = 252) would suggest FT to
      a patient. Almost three-quarters (70.8%, n = 343) agreed FT will become a
      standard option after improvements in patient selection (n = 66) or when its
      effectiveness will be proven (n = 78), or both (n = 199). Most frequently used
      definition of FT was treatment of all significant (life-threatening) cancer foci
      whilst leaving untreated the rest of the gland (39.3%, n = 190). FT use was
      considered as an alternative to whole-gland treatments by 29.7% (n = 144), and to
      AS by 25.0% (n = 121). On multivariate analysis, FT availability and publications
      were associated with a positive opinion on FT. Conversely, attending
      International congresses, treating high PCa volumes and high percentages of high
      risk PCa was associated with a negative opinion. CONCLUSIONS: FT is considered as
      an attractive option for PCa treatment by the European urological community
      sampled by our survey. FT availability positively influences these thoughts. The
      present survey suggests whilst some early adopters already embraced FT, the
      relative majority of the urological community is prone to embrace FT in the near
      future, once current areas of debate are solved.

PMID- 30301699
TI  - Predictive role of changes in the tumor burden and International Metastatic Renal
      Cell Carcinoma Database Consortium class during active surveillance for
      metastatic renal cell carcinoma.
AB  - BACKGROUND: Despite important results achieved for metastatic renal cell
      carcinoma, some patients could benefit from local treatments or an initial active
      surveillance (AS) period for recurrent disease. We aim to analyze: changes in the
      International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk
      class, the number of metastases and the disease burden from the start of AS to
      the beginning of systemic therapy; and if these changes influenced patient
      outcomes. PATIENTS AND METHODS: Patients who started AS at our institution from
      January 2007 to April 2016 were included. The Kaplan-Meier method was used to
      estimate total overall survival (tOS) and progression-free survival. Changes in
      IMDC class, number of metastatic sites, and tumor burden (TB) were evaluated and
      related to patient survival. Among the patients who started active treatment,
      progression-free survival and post surveillance OS (psOS) were evaluated.
      RESULTS: 52 patients were included in the analysis. Median time on AS and tOS
      were 18.3 and 80.1 months respectively. Baseline factors were not related to the
      time on AS apart from the IMDC classification (HR = 2.15; 95% CI: 1.19-3.87; P =
      0.011). The increase in the number of metastatic sites during AS was correlated
      with poor tOS (HR = 2.86; 95% CI: 1.29-6.34; P = 0.010). The increase of the TB
      was a negative prognosis factor for tOS (HR = 1.16; 95% CI: 1.02-1.31; P = 0.024)
      and psOS (HR = 1.21; 95% CI: 1.07-1.40; P = 0.004). Both IMDC class and change in
      the TB at the start of therapy were related to psOS. The retrospective nature and
      the lack of an external review of the imaging are its main limitations.
      CONCLUSIONS: During AS, patients rarely experience a deterioration of their IMDC
      prognostic class, and the change in the TB, more than the increase in the number
      of metastatic sites, may help physicians to make decisions about the early
      termination of AS and the start of systemic therapy.

PMID- 30301700
TI  - Current controversies and developments on the role of lymphadenectomy for penile
      cancer.
AB  - Penile squamous cell carcinoma is a rare cancer in men. The main prognosticators
      of survival for penile cancer patients remain the presence and the extent of
      lymph node metastasis. While radical inguinal lymphadenectomy has been the
      cornerstone of regional lymph node management for many years, it is still
      associated with significant morbidity and psychological distress. Recent
      developments in penile squamous cell carcinoma management have been met with some
      controversy in the urologic oncology community. Herein, we review the current
      controversies and developments on the role of inguinal lymphadenectomy for penile
      cancer.

PMID- 30301701
TI  - Co-infection between Zika and different Dengue serotypes during DENV outbreak in
      Brazil.
AB  - BACKGROUND: The recent introduction of new arboviruses in the Americas, as Zika
      virus (ZIKV) and Chikungunya virus (CHIKV), increased the risk of outbreaks and
      arboviral co-infections. Herein, we report twelve cases of co-infection of ZIKV
      and different DENV serotypes in a city located in the northwest region of Sao
      Paulo State, Brazil, which is hyper-endemic to Dengue. METHODS: Between January
      and November 2016, 1254 suspected cases of arboviral infection were available by
      our surveillance program in Sao Jose do Rio Preto. All suspected patients were
      examined and, when they were arboviral disease-suspectd, had sera separated and
      viral RNA analyzed by PCR/qPCR assays to determine the diagnosis of DENV 1-4,
      ZIKV, or CHIKV in the same samples. After the molecular results, twelve patients
      with ZIKV-DENV coinfection were identified and their clinical and laboratory
      characteristics were described. RESULTS: The mean between symptoms onset and
      collected sample of 3 days. DENV-1 was identified in seven co-infected patients
      and DEN2 in other five. Two patients presented alarm signs of Dengue and no one
      was hospitalized. CONCLUSIONS: The constant presence of co-circulating
      arboviruses increases the chance of co-infection and demonstrates the importance
      of the differential diagnosis, especially during periods of arboviral outbreaks.
      The impact of this co-infection is known individual and collectively.

PMID- 30301702
TI  - BJORL: moving forward, always.

PMID- 30301703
TI  - Sexual Problems of Men With Androgenic Alopecia Treated With 5-Alpha Reductase
      Inhibitors.
AB  - INTRODUCTION: 5-Alpha reductase inhibitors (5-ARIs) are widely used in the
      treatment of benign prostatic hyperplasia (BPH) and androgenic alopecia (AGA).
      AIM: To examine all available data on the effects of 5-ARIs on sexual functioning
      in AGA treatment and to assess whether 5-ARIs increase the risk of sexual
      dysfunction. METHODS: A literature review of publications at PubMed related to
      the subject was used. MAIN OUTCOME MEASURE: We assessed erectile dysfunction,
      ejaculation impairment, and decreased libido. RESULTS: 5-ARIs may cause side
      effects such as erectile dysfunction, ejaculation problems, and decreased libido
      in patients. Their long-term impact and precise mechanism have not been
      clarified. Data from studies on 5-ARIs are important for drug selection and
      patient counseling. More training and awareness is needed for clinicians and
      patients to recover many patients from sexual adverse effects. CONCLUSION: 5-ARIs
      used in the treatment of AGA have well-defined side effects, which can negatively
      affect sexual life. It is unknown and unpredictable which men using these drugs
      may be subject to these side effects and when these effects may appear. Studies
      have been insufficient to provide a clear answer to this question. Coskuner ER,
      Ozkan B, Culha MG. Sexual Problems of Men With Androgenic Alopecia Treated With 5
      Alpha Reductase Inhibitors. Sex Med Rev 2018;XX:XX-XX.

PMID- 30301704
TI  - Exo-Clinical Trials of Nutritional Supplements for Sexual Dysfunction:
      Precedents, Principles, and Protocols.
AB  - INTRODUCTION: Care-seeking for sexual dysfunction is limited by embarrassment,
      efficacy/safety concerns, and cost. Nutritional supplements (NSs) are low-cost
      but unproven. AIM: To provide hypotheses on whether effective NS combinations for
      sexual dysfunction can be created following known pharmacology principles and
      tested with sufficient rigor in Internet-based "exo-clinical" trials (XCTs).
      METHODS: PubMed and Google searches were conducted to review the feasibility of
      XCTs of NS combinations for sexual dysfunction. Findings were synthesized into
      recommendations for XCTs to treat the most common sexual problems. MAIN OUTCOME
      MEASURE: The hierarchy of references used for making recommendations was
      controlled clinical trials over uncontrolled trials. The frequency of sexual
      dysfunction was determined in population-representative national surveys.
      RESULTS: XCTs of cognitive behavioral therapy show conclusive efficacy for
      anxiety and depression. 5 small XCTs showed efficacy for female sexual
      dysfunction and erectile dysfunction (ED), and 2 XCTs of NS for other medical
      problems substantiated feasibility. To test the feasibility of XCTs for the most
      common forms of sexual dysfunction-ED, hypoactive sexual desire disorder (HSDD),
      and sexual performance anxiety-protocol outlines were generated for frugal XCTs;
      the total estimated subject time burden is <=1 hour. CONCLUSION: An XCT is a cost
      effective method of evaluating new treatments, including sexual dysfunction and
      common mental disorders, if compliance is maintained by regular outreach while
      minimizing the time burden on subjects and handling consent and privacy issues
      appropriately. NS combinations might expand the opportunities for relief of
      sexual dysfunction if formulated with pharmacologically active doses of NS with
      already supported efficacy and safety. The feasibility of XCTs of NS combinations
      for sexual dysfunction might be tested most productively in men with ED, in women
      with HSDD, and in men and women with sexual performance anxiety. Pyke RE. Exo
      Clinical Trials of Nutritional Supplements for Sexual Dysfunction: Precedents,
      Principles, and Protocols. Sex Med Rev 2018;XX:XX-XX.

PMID- 30301705
TI  - The Effect of Pelvic Floor Muscle Exercise on Female Sexual Function During
      Pregnancy and Postpartum: A Systematic Review.
AB  - INTRODUCTION: Pelvic floor muscle exercise (PFME) is recommended as a first-line
      treatment for urinary incontinence. However, a review of the literature suggests
      the effect of PFME on sexual function (SF), particularly during pregnancy and the
      postpartum period, is understudied. AIM: To assess the effect of PFME on SF
      during pregnancy and the postpartum period. METHODS: The following databases were
      searched: CINAHL (EBSCOhost), Health Collection (Informit), PubMed (National
      Center for Biotechnology Information), Embase (Ovid), MEDLINE, Cochrane, Health
      Source, Scopus, Wiley, Health & Medical Complete (ProQuest), Joanna Briggs
      Institute, and Google Scholar. Results from published randomized controlled
      trials (RCTs) and non-RCTs from 2004 to January 2018 on pregnant and postnatal
      women were included. PEDro and Critical Appraisal Skills Programme scores were
      used to assess the quality of studies. Data were analysed using a qualitative
      approach. MAIN OUTCOME MEASURE: The primary outcome was the impact of antenatal
      or postnatal PFME on at least 1 SF variable, including desire, arousal, orgasm,
      pain, lubrication, and satisfaction. The secondary outcome was the impact of PFME
      on PFM strength. RESULTS: We identified 10 studies with a total of 3607
      participants. These included 4 RCTs, 1 quasi-experimental study, 3 interventional
      cohort studies, and 2 long-term follow up cohort studies. No studies examined the
      effect of PFME on SF during pregnancy. 7 studies reported that PFME alone
      improved sexual desire, arousal, orgasm, and satisfaction in the postpartum
      period. CONCLUSION: The current data needs to be interpreted in the context of
      the studies' risk of bias, small sample sizes, and varying outcome assessment
      tools. The majority of the included studies reported that postnatal PFME was
      effective in improving SF. However, there is a lack of studies describing the
      effect of PFME on SF during pregnancy, and only minimal data are available on the
      postpartum period. More RCTs are needed in this area. Sobhgol SS, Priddis H,
      Smith CA, et al. The Effect of Pelvic Floor Muscle Exercise on Female Sexual
      Function During Pregnancy and Postpartum: A Systematic Review. Sex Med Rev
      2018;XX:XX-XX.

PMID- 30301706
TI  - Genital Sensations in Persistent Genital Arousal Disorder: A Case for an
      Overarching Nosology of Genitopelvic Dysesthesias?
AB  - INTRODUCTION: Persistent genital arousal disorder (PGAD) is a highly distressing
      and poorly understood condition characterized by unwanted sensations of genital
      arousal in the absence of subjective sexual desire. Research has shown that some
      individuals with PGAD also report orgasm, urinary, and pain symptoms, with 1
      recent study specifically comparing a "painful persistent genital arousal
      symptom" group to a "non-painful persistent genital arousal symptom" group on
      various indicators given the highly frequent report of comorbid genitopelvic pain
      in their sample. AIM: To review literature on PGAD focusing on the presence of
      pain symptoms. METHODS: A literature review through May 2018 was undertaken to
      identify articles that discuss pain characteristics in individuals with
      persistent sexual arousal syndrome, persistent genital arousal disorder, symptoms
      of persistent genital arousal, and restless genital syndrome. MAIN OUTCOME
      MEASURE: A review of pain/discomfort associated with persistent genital arousal,
      and the proposal of a new theoretical framework of genitopelvic dysesthesias.
      RESULTS: PGAD is a distressing condition that is associated with a significant,
      negative impacts on psychosocial and daily functioning. Although it is clear that
      unwanted and persistent genital arousal is the hallmark symptom of PGAD, symptoms
      of pain and discomfort are also frequently reported. Based on the results of this
      review, a model of genitopelvic dysesthesias is proposed, with subcategories of
      unpleasant sensations that are based on patients' primary complaint: arousal,
      arousal and pain, or pain (and other sensations). CONCLUSION: The proposed model
      can provide an important framework for conceptualizing conditions characterized
      by unpleasant genitopelvic sensations. A model such as this one can benefit
      highly misunderstood conditions that are questioned in terms of their legitimacy
      and severity-such as PGAD-by conceptualizing them as sensory disorders, which in
      turn can reduce stigma, unify research efforts, and potentially improve access to
      care. Pukall CF, Jackowich R, Mooney K, et al. Genital Sensations in Persistent
      Genital Arousal Disorder: A Case for an Overarching Nosology of Genitopelvic
      Dysesthesias? Sex Med Rev 2018;XX:XXX-XXX.

PMID- 30301707
TI  - The Serendipitous Story of Sildenafil: An Unexpected Oral Therapy for Erectile
      Dysfunction.
AB  - INTRODUCTION: The serendipitous discovery of sildenafil (Viagra [sildenafil
      citrate]) as a treatment for erectile dysfunction (ED) is one of the most
      fascinating drug development stories of our time. When sildenafil was approved by
      the U.S. Food and Drug Administration in 1998, it revolutionized the treatment
      protocol for men with ED, once considered a psychological issue or an inevitable
      part of aging. AIM: To review the discovery of sildenafil and its role in
      changing the field of sexual medicine in the context of the epidemiology and
      history of treatment for ED. METHODS: For this narrative review, a literature
      search was conducted to identify essential articles and was supplemented by
      author observations from a historical perspective. MAIN OUTCOME MEASURE: A broad
      overview of ED and its past, current, and future treatments. RESULTS: ED is a
      prevalent condition for which medical treatment had been limited to genitally
      localized interventions, including surgery, vacuum pumps, injectable therapies,
      and intraurethral suppositories. The discovery of sildenafil provided a safe,
      oral pharmacotherapy for the treatment of ED, sparking greater understanding of
      the science behind ED and its role in men's overall health. CONCLUSION: The
      approval of sildenafil initiated a global conversation about ED that had profound
      implications for patients, methods of clinical practice, and academic sexual
      medicine. These changes will catalyze continued advances in ED treatment.
      Goldstein I, Burnett AL, Rosen RC, et al. The serendipitous story of sildenafil:
      an unexpected oral therapy for erectile dysfunction. Sex Med Rev 2018;XX:XXX-XXX.

PMID- 30301708
TI  - New Developments in Surgical Treatment for Penile Size Preservation in Peyronie's
      Disease.
AB  - INTRODUCTION: Peyronie's disease (PD) is associated with penile length loss due
      to atrophy that occurs as a result of fibrous inelastic scarring. Studies have
      shown diminished penile length and girth, as well as the inability to participate
      in sexual activity, can lead to decreased quality of life, emotional challenges,
      and sexual dissatisfaction in a large percentage of men. AIM: To provide a
      summary of the new developments in the surgical techniques available for the PD
      patient, with a focus on procedures that provide penile size restoration.
      METHODS: A MEDLINE PubMed search was used to identify articles related to
      surgical treatments for PD, including plication procedures, penile prosthesis
      placement, and techniques for size restoration. MAIN OUTCOME MEASURE: Types of
      surgical treatments for PD and their outcomes regarding penile length and patient
      satisfaction. RESULTS: The Nesbit procedure, among other plication procedures,
      and penile prosthesis placement with modeling or plication are likely to decrease
      penile length. Although plaque incision with grafting offers restoration of
      penile length, it carries a risk of postoperative erectile dysfunction (ED). For
      men with concomitant ED and severe curvature not amenable to prosthesis with
      modeling or plication, options include grafting, circumferential tunical
      incisions, subcoronal prosthesis placement, and the sliding technique with its
      modifications, allowing for management of both PD and ED while restoring penile
      length. Adjunct procedures, such as ventral phalloplasty and suspensory ligament
      release, have also been shown to restore length in PD patients. Novel therapies
      continue to evolve with the goal of preserving length while treating curvature.
      CONCLUSION: There are numerous surgical options for correcting penile curvature
      in PD patients, with or without concomitant ED treatment. When determining the
      optimal procedure, it is important to consider possible preservation of penile
      length and to discuss possible complications to increase patient satisfaction and
      improve quality of life. Barrett-Harlow B, Clavell-Hernandez J, Wang R. New
      Development in Surgical Treatment for Size Preservation in Peyronie's Disease.
      Sex Med Rev 2018;XX:XX-XX.

PMID- 30301709
TI  - Toll-like receptor 2 and 4 polymorphisms associated with Helicobacter pylori
      susceptibility and gastric cancer.
AB  - BACKGROUND/AIMS: Genetic polymorphisms in Toll-like receptors (TLRs) are
      important influence on gastric lesion development and Helicobacter pylori
      susceptibility. MATERIALS AND METHODS: TLR2 rs3804099 and rs3804100 and TLR4
      rs10759932 were determined in a total of 400 patients. The association among
      genotypes and the risk of gastric lesion development and H. pylori susceptibility
      were evaluated by the odds ratios (ORs) and 95% confidence intervals (95% CIs)
      from logistic regression analyses. RESULTS: TLR4 rs10759932, C/C homozygous
      genotype was associated with an increased risk of premalignant/malignant
      (OR=2.48, 95% CI=1.96-4.62, p=0.015). The recessive model of TLR4 rs10759932
      showed a decreased risk of H. pylori susceptibility (adjusted OR=0.52, 95%
      CI=0.38-0.82, p=0.046). Meanwhile, the recessive model was associated with an
      increased risk of non-malignant (OR=3.46, 95% CI=2.25-5.67, p=0.001). In subjects
      with H. pylori infection, the recessive model was associated with an increased
      risk of non-malignant (OR=2.28, 95% CI=1.24-3.57, p=0.001) and
      premalignant/malignant (OR=1.83, 95% CI=1.16-2.84, p=0.027). CONCLUSION: TLR4
      rs10759932, but not TLR2 rs3804099 and rs3804100, was associated with risk of
      premalignant and/or malignant and H. pylori susceptibility. H. pylori infection
      seems to contribute to chronic gastritis, and premalignant/malignant supported
      the development of the premalignant/malignant lesions involved in H. pylori
      infection that is critical to gastric cancer in Thai patients.

PMID- 30301710
TI  - Results of positive proximal margin after resection for hilar cholangiocarcinoma:
      An analysis of 42 cases.
AB  - BACKGROUND/AIMS: Hilar cholangiocarcinoma (HC) is a tumor that invades the
      confluence of the left and right hepatic bile ducts. Surgery is the definitive
      treatment but is also technically demanding. Here, we report our experience on 42
      patients who underwent surgical resection for HC. The aim of the present study
      was to evaluate the margin status of resected specimens on frozen sections and
      the impact of R1 resection margin on survival. MATERIALS AND METHODS: A total of
      42 patients with HC who underwent surgical resection in our clinic between
      January 2008 and January 2017 were included in the study. Patients' charts were
      evaluated retrospectively. RESULTS: The 1-, 2-, and 4-year overall survival rates
      of the 42 patients were 76.2%, 40%, and 10.7%, respectively. The median survival
      rates of the patients with negative and positive proximal surgical margins were
      22 (11.93-32.06) and 17 (14.43-19.56) months, respectively. There was no
      statistically significant difference between these two groups. CONCLUSION: In HC,
      surgery achieving negative proximal surgical margin is often very difficult. Our
      results demonstrate that frozen sections are reliable for the assessment of the
      invasion status of the proximal and distal ductal surgical margins. Although
      complete resection is potentially curative, survival of the patients with HC is
      still poor. If there is no distant metastasis at the time of diagnosis, then
      extirpating surgery should be encouraged as survival of the patients with
      positive and negative margins is not significantly different.

PMID- 30301711
TI  - Incidence and epidemiological features of acute pancreatitis among adult
      inhabitants in Qatar.
AB  - BACKGROUND/AIMS: Acute pancreatitis (AP) is one of the most common
      gastrointestinal causes of hospital admission in Qatar. The aim of the present
      study was to investigate the epidemiological features and demographic
      characteristics of patients with AP and to estimate the annual incidence rates of
      this disease among adult inhabitants in Qatar. MATERIALS AND METHODS: This
      retrospective study was conducted using the data collected by reviewing records
      of patients with AP admitted to the medical and surgical wards of Hamad
      GeneralHospital and Alkhor Hospital, Qatar from January 2007 to December 2012.
      Diagnosis of AP was based on abdominal pain suggestive of AP, serum lipase and/or
      amylase at least three times the upper limit of normal, and/or characteristic
      findings of AP on abdominal ultrasound or computed tomography. RESULTS: A total
      of 382 AP events were reported in 334 patients. There were 250 (75%) males and 84
      (25%) females. The mean age (+/-SD) of the patients was 56.8+/-18.7 years.
      Gallstone disease (40.6%) was the highest cause of AP, followed by alcohol
      consumption (28.5%) and idiopathic AP (20.7%). The mean annual incidence rate of
      AP was 5 per 100,000 adult inhabitants in Qatar from January 2007 to December
      2012. The incidence rate among men was higher than that among women. Mortality
      rate was low (0.3%), and there were complications in 112 (29.3%) patients.
      CONCLUSION: The annual incidence rate of AP is relatively low in Qatar and tends
      to behave similar to many European countries in etiology, which can be explained
      by population structure. Gallstone and alcohol consumption are the main causes,
      and idiopathic AP is responsible for more cases than expected.

PMID- 30301712
TI  - [Online information system for -phytotherapy in animals].
AB  - INTRODUCTION: Phytotherapy becomes increasingly popular in veterinary medicine.
      To fully exploit the therapeutic potential of medicinal plants and ensure their
      safe use, knowledge about the effective plant parts and preparations is required.
      Improper use and overdosage of medicinal plants can be toxic. With
      www.phytoarznei.ch, we provide an online decision support aid that allows for the
      retrieval of currently available information on medicinal plants and their use in
      domestic animals. This decision support system is based on the available
      literature in the field, which after critical evaluation has been incorporated
      into a structured database. For each medicinal plant or drug, we have listed
      therapeutic indications, different application types, organoleptic properties,
      plant ingredients, pharmacological effects, dosages, duration of treatment,
      toxicity, legal frame for use in livestock and relevance for doping. A user
      friendly access to all data is achieved by means of two search programs, either
      by entering the plant name or name of the drug in a search field or by selecting
      the desired animal species and therapeutic application from respective drop-down
      lists. This database on medicinal plant applications in animals is linked to the
      poisonous plant database of the University of Zurich and, for marketed
      preparations, to the Swiss compendium of veterinary medicinal products as well as
      to an index of related veterinary products.

PMID- 30301714
TI  - [Vaccinovigilance: Reports of adverse reactions in the year 2017].
AB  - INTRODUCTION: The aim of the Vaccinovigilance system is the identification of
      adverse reactions and rare events after the use of immunological veterinary
      medicinal products. In the year 2017, 128 reports of adverse reactions following
      the application of various authorized vaccines were received and evaluated. The
      notifications were submitted primarily by marketing authorization holders (96) or
      veterinarians (27) and private persons (5). As in previous years, dogs were
      involved in most of the adverse effects (55%), followed by cattle (18%) and swine
      (10%). Unlike the previous years, significantly fewer reports were submitted on
      cats (8%). The correlation between reaction and vaccination was considered
      probable in 43% of the - cases.

PMID- 30301715
TI  - Knee osteoarthritis and bisphosphonates: Could BCP crystals be the missing link?

PMID- 30301713
TI  - [Defining daily doses and total doses for the measurement of antibiotic usage in
      Swiss pig production].
AB  - INTRODUCTION: A significant Antibiotic-Monitoring-System is essential to analyse
      the use of antibiotics and to a better understanding of trends in resistance
      development. In human and veterinary medicine, for example, a system based on
      defined daily and treatment doses (Defined Daily Dose: DDD and Defined Course
      Dose: DCD) is applied. These definitions can be used to estimate the number of
      treatment days and treatments with antimicrobial agents in a population. For
      veterinary medicine, the European Medicines Agency (EMA) has published the
      European values DDDvet and DCDvet in the farm animal sector. The aim of this
      study was to define Swiss daily and treatment doses (DDDch and DCDch) for the
      treatment of pigs and to compare them with the EMA values in order to investigate
      the differences between individually collected national doses and average
      international doses. For the comparison, the quotient of Swiss and European
      values was calculated and the influence of the application form of an active
      substance and the number of active substances contained in a preparation was
      investigated. One hundred and three veterinary preparations with 138 active
      substances were assigned a DDDch and DCDch value. A comparison with EMA values
      was possible for 118 active substances. The comparison showed median values of
      0.91 for the daily doses and 0.90 for the treatment doses, so that the daily and
      treatment doses in Switzerland are lower than the corresponding EMA doses. Both
      the form of application (injection solutions: 1.00; premixes: 0.76; P=0.02) and
      the number of active substances in the preparation (one active substance: 1.00;
      two active substances: 0.76; three active substances: 0.43; each P.

PMID- 30301716
TI  - Tapering Janus kinase inhibitors in rheumatoid arthritis with low disease
      activity or remission: reality or dream?

PMID- 30301718
TI  - What did the party conferences tell us about the NHS and social care?

PMID- 30301717
TI  - Global warming: experts demand urgent action to prevent public health crisis.

PMID- 30301719
TI  - Inflammatory signals directly instruct PU.1 in HSCs via TNF.
AB  - The molecular mechanisms governing the transition from hematopoietic stem cells
      (HSCs) to lineage-committed progenitors remain poorly understood. Transcription
      factors (TFs) are powerful cell intrinsic regulators of differentiation and
      lineage commitment, while cytokine signaling has been shown to instruct the fate
      of progenitor cells. However, the direct regulation of differentiation-inducing
      hematopoietic TFs by cell extrinsic signals remains surprisingly difficult to
      establish. PU.1 is a master regulator of hematopoiesis and promotes myeloid
      differentiation. Here we report that TNF can directly and rapidly up-regulate
      PU.1 protein in HSCs in vitro and in vivo. We demonstrate that in vivo, niche
      derived TNF is the principal PU.1 inducing signal in HSCs and is both sufficient
      and required to relay signals from inflammatory challenges to HSCs.

PMID- 30301720
TI  - Implementation of a pharmacogenomics education program for pharmacists.
AB  - PURPOSE: The development, implementation, and evaluation of a pharmacogenomics
      education program for pharmacists in a large, integrated multicampus health
      system are described. SUMMARY: Pharmacogenomics has been described as tailoring
      medications to each patient's unique genetic sequence with the goals of
      minimizing harmful effects and optimizing therapeutic effects. Pharmacists are
      uniquely trained to lead the implementation of pharmacogenomics in clinical care.
      After assessment of pharmacists' comfort with pharmacogenomics, different
      approaches were explored to develop, pilot test, and disseminate pharmacogenomics
      education across a multicampus academic medical center. Limited success with
      large-audience, single-lecture didactic education led to development and delivery
      of targeted, competency-based online modules using the institution's academic
      virtual learning environment and course management system. Implementation steps
      included (1) collaboration with the Mayo Clinic Center for Individualized
      Medicine to create an interprofessional development team and project charter, (2)
      galvanizing pharmacy leadership support across multiple campuses, (3) development
      of competency-based interactive modules, and (4) assessment of the quality of and
      learner satisfaction with the modules. Significant improvements in competency
      scores were observed with each module and across the multiple campuses.
      Satisfaction with the education program was assessed at the end of a 4-module
      series. CONCLUSION: A pharmacogenomics educational program targeting pharmacists
      was developed through interprofessional collaboration and provided a novel
      opportunity to construct an educational infrastructure to support enterprise
      health-system campuses with limited educational resources.

PMID- 30301721
TI  - Transition from treprostinil to selexipag in patients with pulmonary arterial
      hypertension: Case series.
AB  - PURPOSE: Safe transition of patients with pulmonary arterial hypertension (PAH)
      from parenteral treprostinil to oral selexipag therapy in both inpatient and
      outpatient settings is described. SUMMARY: There is a paucity of published data
      on how to safely transition patients to oral therapy in the event of
      complications and problems during parenteral administration of prostacyclins,
      which can include bloodstream infections, injection-site pain (with use of
      subcutaneous treprostinil), infusion pump malfunction, and dosing errors due to
      incorrect dose preparation. This case series describes the transition of 4
      patients with World Health Organization (WHO) group I PAH (WHO functional classes
      II-IV) from i.v. (n = 3) and subcutaneous (n = 1) treprostinil infusion therapy
      to oral selexipag use. The transition process was completed through the use of 2
      cross-titration methods (rapid and slow). A rapid approach was used in 2 cases
      involving inpatients, with parenteral-to-oral transition completed over 8-13
      days; a slow transition method was used in 2 cases, in which outpatients
      completed the transition over 19-25 weeks. Adverse events during the transitions
      were headache, nausea, vomiting, diarrhea, and jaw pain. CONCLUSION: Four
      patients with WHO group I PAH who were not candidates for continued parenteral
      treprostinil therapy were safely transitioned to oral selexipag in both inpatient
      and outpatient settings.

PMID- 30301722
TI  - Canadians quit World Medical Association over president's plagiarised speech.

PMID- 30301723
TI  - Low risk cancer: recalibrate rather than just rename?

PMID- 30301724
TI  - Transparency in clinical trial reporting.

PMID- 30301725
TI  - Cerebral fat embolism syndrome (FES): similar cases with different outcomes.
AB  - Fat embolism syndrome (FES) is a rare multisystem, clinical syndrome occurring in
      0.9%-2.2% of long-bone fractures. The severity of FES can vary from subclinical
      with mild respiratory changes and haematological aberrations to a fulminant state
      characterised by sudden onset of severe respiratory and neurological impairment.
      Here we present two patients with cerebral FES secondary to femur fracture. Both
      patients exhibited profound neurological impairment with varied outcomes. Our
      cases highlight the importance of a high clinical suspicion of FES in patients
      with long-bone fractures and neurological deterioration. We recommend early plate
      osteosynthesis to prevent additional emboli in patients with FES and situational
      placement of intracranial pressure monitoring. Finally, cerebral FES has low
      mortality even in a patient with tentorial herniation and fixed, dilated pupils.

PMID- 30301726
TI  - Visual deficit possibly caused by lutetium-177 PSMA treatment.
AB  - This report describes a case of a 54-year-old man who underwent lutetium-177-PSMA
      therapy in the setting of metastatic castration-resistant prostate cancer (mCRPC)
      in the University Medical Center Utrecht. Following administration of the second
      cycle, patient presented with a slowly impairing, bilateral visual loss. This
      clinical presentation was most likely the result of the high intracranial
      pressure due to impediment of cerebrospinal fluid circulation, possibly related
      to obstructive dural thickness, being either caused by dural and/or
      leptomeningeal metastases of advanced mCRPC or by local radiation effects
      following lutetium-177-PSMA therapy. Describing this case, we aim to add to the
      discussion on 177Lu-PSMA safety, in which prospective research will ultimately
      offer definite answers.

PMID- 30301727
TI  - Fluoxetine overdose in a teenager resulting in serotonin syndrome, seizure and
      delayed onset rhabdomyolysis.
AB  - A 14-year-old young adult took an overdose of 1.2 g of fluoxetine, a selective
      serotonin reuptake inhibitor (SSRI) that he had been prescribed for depression.
      He had a generalised tonic/clonic seizure at 6 hours postingestion.After the
      seizure, he developed signs consistent with serotonin syndrome: fine tremor,
      agitation, sweating and hyperreflexia. This was followed by severe muscle pain
      and rhabdomyolysis with peak creatine kinase (CK) of 33 941 at 74 hours. He was
      managed with intravenous fluids and analgesia and discharged after 4 days, having
      avoided renal injury. The use of SSRI's such as fluoxetine in teenagers has
      increased in recent years. While it is generally considered benign in overdose,
      this report illustrates the severe consequences of overdose at high quantities
      and discusses appropriate management in these cases. We note that in this case,
      there was a delayed onset of rhabdomyolysis with peak CK at 74 hours
      postingestion.

PMID- 30301728
TI  - Two distinct histological Richter's transformations 23 years apart in a patient
      with chronic lymphocytic leukaemia.
AB  - A 53-year-old man with a 1-year history of chronic lymphocytic leukaemia (CLL)
      presented with a left bicep mass. Biopsy and staging workup revealed Richter's
      transformation (RT) Ann Arbor stage 1E diffuse large B-cell lymphoma in the
      bicep. The patient was treated with combination chemotherapy with
      cyclophosphamide, doxorubicin, Vincristine and prednisone followed by site
      radiation and did well thereafter. His CLL progressed and required treatment on
      two more occasions 11 and 18 years after his initial diagnosis with fludarabine,
      Cytoxan and Rituxan and then with bendamustine and rituximab. 23 years after
      initial presentation, he developed diffuse lymphadenopathy and B-symptoms. A
      biopsy of an enlarged cervical lymph node demonstrated only CLL for which he was
      started on ibrutinib. Treatment was shortly discontinued thereafter due to
      intolerance and worsening symptoms. A second biopsy was performed which revealed
      concurrent CLL and Hodgkin's lymphoma representing a second and histologically
      distinct RT.

PMID- 30301729
TI  - Severe pneumonitis refractory to steroids following anti-PD-1 immunotherapy.
AB  - Anti-programmed death 1 (PD-1) immune checkpoint inhibitors enhance the
      antitumour activity of the immune system and have produced durable tumour
      responses in several solid tumours including non-small cell lung cancer (NSCLC).
      However, PD-1 inhibitors can lead to immune-related adverse events , including
      pneumonitis, which is typically mild, but can be severe and potentially fatal.
      Pneumonitis often resolves with steroids, but some cases are steroid refractory,
      leading to a relapsing and remitting course in milder cases or the need for
      salvage therapies in more severe cases. Here, we present two patients with NSCLC
      who developed severe pneumonitis following therapy with nivolumab and
      pembrolizumab. While one patient improved with steroids and infliximab, the other
      patient failed to respond to steroids and subsequently died. These cases
      demonstrate the highly variable presentation and therapeutic responses seen in
      patients with pneumonitis following anti-PD-1 therapy and illustrate that severe
      cases can often present refractory to steroid therapy.

PMID- 30301730
TI  - Lady with 'lobster claw' feet.
AB  - A 94-year-old woman admitted with confusion secondary to a urinary tract
      infection exhibited deformities in all four limbs that were present from birth.
      Her appearance was suggestive of split hand/split foot malformation a rare
      congenital condition that affects the central rays of the distal limb portion.
      She had no syndromic features and had lived without support or assistance of her
      daily activities. A keen knitter, she regularly knitted for her three
      grandchildren, all of which, along with her son, were unaffected by this
      condition.

PMID- 30301731
TI  - Ascites with hepatic extravasation of total parenteral nutrition (TPN) secondary
      to umbilical venous catheter (UVC) malposition in an extremely preterm baby.
AB  - The ease of access and advantages of a secure central line makes use of umbilical
      venous catheter (UVC) and umbilical artery catheters a part of the standard of
      care in the extremely premature babies in the neonatal intensive care unit.
      However, there are complications associated with their use. One of the uncommon
      complications reported is total parenteral nutrition (TPN) ascites secondary to
      vessel perforation or hepatic erosion by the tip of the catheter due to
      malposition of a UVC. We present here a case of such catheter perforation causing
      ascites and right hepatic collection of TPN in a 28-week-old infant. Abdominal
      paracentesis was therapeutic by relieving the distension as well as confirming
      the presence of parenteral nutrition in the peritoneal cavity.

PMID- 30301732
TI  - DRESS syndrome-associated acute necrotizing eosinophilic myocarditis with giant
      cells.
AB  - Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an
      uncommon drug hypersensitivity reaction caused by a wide variety of agents. It
      has a characteristic latent period between 2 and 8 weeks from the onset of drug
      ingestion followed by a slow resolution with the potential for relapse. Despite
      being a potentially fatal disease, little is understood about its variable
      clinical presentation and why it can present long after removal of the offending
      drug. Visceral organ involvement typically occurs, but rarely results in
      clinically manifested cardiac injury. In its most aggressive form, acute
      necrotizing eosinophilic myocarditis (ANEM) can present with DRESS. We present an
      unusual case of DRESS syndrome due to lamotrigine with confirmed ANEM showing
      both eosinophils and rare giant cell infiltrates on endomyocardial biopsy.
      Although lamotrigine has been reported to cause DRESS, it has not been previously
      implicated as a cause of ANEM.

PMID- 30301733
TI  - Case of drug reaction with eosinophilia and systemic symptoms secondary to
      vancomycin.

PMID- 30301734
TI  - Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic
      athletes: a randomised clinical trial.
AB  - OBJECTIVE: Normal-weight oligo-amenorrhoeic athletes (OAA) are at risk for low
      bone mineral density (BMD). Data are lacking regarding the impact of oestrogen
      administration on bone outcomes in OAA. Our objective was to determine the
      effects of transdermal versus oral oestrogen administration on bone in OAA
      engaged in weight-bearing activity. METHODS: 121 patients with OAA aged 14-25
      years were randomised to receive: (1) a 17beta-estradiol transdermal patch
      continuously with cyclic oral micronised progesterone (PATCH), (2) a combined
      ethinyl estradiol and desogestrel pill (PILL) or (3) no oestrogen/progesterone
      (NONE). All participants received calcium and vitamin D supplementation. Areal
      BMD was assessed at the lumbar spine, femoral neck, total hip and total body less
      head using dual-energy X-ray absorptiometry at baseline, 6 and 12 months.
      Intention-to-treat (ITT) and completers analyses were performed. RESULTS:
      Randomised groups did not differ for age, body mass index or BMD Z-scores at
      baseline. For ITT analysis, spine and femoral neck BMD Z-scores significantly
      increased in the PATCH versus PILL (p=0.011 and p=0.021, respectively) and NONE
      (p=0.021 and p=0.033, respectively) groups, and hip BMD Z-scores significantly
      increased in the PATCH versus PILL group (p=0.018). Similar findings were noted
      in completers analysis. CONCLUSION: Transdermal estradiol over 12 months improves
      BMD in young OAA, particularly compared with an ethinyl estradiol-containing
      contraceptive pill/oral contraceptives. TRIAL REGISTRATION NUMBER: NCT00946192;
      Pre-results.

PMID- 30301735
TI  - Topical glyceryl trinitrate for the treatment of tendinopathies: a systematic
      review.
AB  - OBJECTIVE: To produce a best evidence synthesis of the clinical effects of
      topical glyceryl trinitrate (GTN) in the treatment of tendinopathies. DESIGN: A
      systematic review of published randomised controlled trials (RCTs) of the use of
      GTN in patients with tendinopathy. DATA SOURCES: MEDLINE, Embase, Scopus and
      CINAHL from database inception to January 2018. METHODS: We examined RCTs
      comparing the effects of topical GTN with either placebo or other treatments on
      tendinopathy. Overall quality of each eligible study was determined based on a
      combined assessment of internal validity, external validity and precision. The
      level of evidence for each assessed parameter was rated based on the system by
      van Tulder et al. RESULTS: A total of 10 eligible RCTs were identified including
      patients with tendinopathy of the rotator cuff (n=4), wrist extensors (n=3),
      Achilles (n=2) and patellar (n=1) tendons. For all tendinopathies, improvements
      in pain were significant when comparing GTN versus placebo in the short term (<8
      weeks; poor evidence). Significant improvements in midterm outcomes for treatment
      with GTN versus placebo included the following: patient satisfaction (strong
      evidence); chances of being asymptomatic with activities of daily living (strong
      evidence); range of movement (moderate evidence); strength (moderate evidence);
      pain (at night and with activity; poor evidence) and local tenderness (poor
      evidence). Patients treated with topical GTN reported a higher incidence of
      headaches than those who received placebo (moderate evidence). CONCLUSIONS AND
      RELEVANCE: Treatment of tendinopathies with topical GTN for up to 6 months
      appears to be superior to placebo and may therefore be a useful adjunct to the
      treating healthcare professions.

PMID- 30301736
TI  - Glucocorticoid-Induced Leucine Zipper Promotes Neutrophil and T-Cell Polarization
      with Protective Effects in Acute Kidney Injury.
AB  - The glucocorticoid-induced leucine zipper (GILZ) mediates anti-inflammatory
      effects of glucocorticoids. Acute kidney injury (AKI) mobilizes
      immune/inflammatory mechanisms, causing tissue injury, but the impact of GILZ in
      AKI is not known. Neutrophils play context-specific proinflammatory [type 1
      neutrophil (N1)] and anti-inflammatory [type 2 neutrophil (N2)] functional roles.
      Also, regulatory T lymphocytes (Tregs) and regulatory T-17 (Treg17) cells exert
      counterinflammatory effects, including the suppression of effector T lymphocytes
      [e.g., T-helper (Th) 17 cells]. Thus, utilizing cell preparations of mice kidneys
      subjected to AKI or sham operation, we determined the effects of GILZ on T cells
      and neutrophil subtypes in the context of its renoprotective effect; these
      studies used the transactivator of transcription (TAT)-GILZ or the TAT peptide.
      AKI increased N1 and Th-17 cells but reduced N2, Tregs, and Treg17 cells in
      association with increased interleukin (IL)-17+ but reduced IL-10+ cells
      accompanied with the disruption of mitochondrial membrane potential (psi m) and
      increased apoptosis/necrosis compared with sham kidneys. TAT-GILZ, compared with
      TAT, treatment reduced N1 and Th-17 cells but increased N2 and Tregs, without
      affecting Treg17 cells, in association with a reduction in IL-17+ cells but an
      increase in IL-10+ cells; TAT-GILZ caused less disruption of psi m and reduced
      cell death in AKI. Importantly, TAT-GILZ increased perfusion of the ischemic
      reperfused kidney but reduced tissue edema compared with TAT. Utilizing splenic T
      cells and bone marrow-derived neutrophils, we further showed marked reduction in
      the proliferation of Th cells in response to TAT-GILZ compared with response to
      TAT. Collectively, the results indicate that GILZ exerts renoprotection
      accompanied by the upregulation of the regulatory/suppressive arm of immunity in
      AKI, likely via regulating cross talk between T cells and neutrophils.

PMID- 30301737
TI  - Genotype-by-Environment-by-Environment Interactions in the Saccharomyces
      cerevisiae Transcriptomic Response to Alcohols and Anaerobiosis.
AB  - Next generation biofuels including longer-chain alcohols such as butanol are
      attractive as renewable, high-energy fuels. A barrier to microbial production of
      butanols is the increased toxicity compared to ethanol; however, the cellular
      targets and microbial defense mechanisms remain poorly understood, especially
      under anaerobic conditions used frequently in industry. Here we took a
      comparative approach to understand the response of Saccharomyces cerevisiae to 1
      butanol, isobutanol, or ethanol, across three genetic backgrounds of varying
      tolerance in aerobic and anaerobic conditions. We find that strains have
      different growth properties and alcohol tolerances with and without oxygen
      availability, as well as unique and common responses to each of the three
      alcohols. Our results provide evidence for strain-by-alcohol-by-oxygen
      interactions that moderate how cells respond to alcohol stress.

PMID- 30301738
TI  - 10q23.31 microduplication encompassing PTEN decreases mTOR signalling activity
      and is associated with autosomal dominant primary microcephaly.
AB  - BACKGROUND: Hereditary primary microcephaly (MCPH) is mainly characterised by
      decreased occipitofrontal circumference and variable degree of intellectual
      disability. MCPH with a dominant pattern of inheritance is a rare condition, so
      far causally linked to pathogenic variants in the ALFY, DPP6, KIF11 and DYRK1A
      genes. OBJECTIVE: This study aimed at identifying the causative variant of the
      autosomal dominant form of MCPH in a Brazilian family with three affected
      members. METHODS: Following clinical evaluation of two sibs and their mother
      presenting with autosomal dominant MCPH, array comparative genome hybridisation
      was performed using genomic DNA from peripheral blood of the family members. Gene
      and protein expression studies were carried out in cultured skin fibroblasts.
      RESULTS: A 382 kb microduplication at 10q23.31 was detected, encompassing the
      entire PTEN, KLLN and ATAD1 genes. PTEN haploinsufficiency has been causally
      associated with macrocephaly and autism spectrum disorder and, therefore, was
      considered the most likely candidate gene to be involved in this autosomal
      dominant form of MCPH. In the patients' fibroblasts, PTEN mRNA and protein were
      found to be overexpressed, and the phosphorylation patterns of upstream and
      downstream components of the mammalian target of rapamycin (mTOR) signalling
      pathway were dysregulated. CONCLUSIONS: Taken together, our results demonstrate
      that the identified submicroscopic 10q23.31 duplication in a family with MCPH
      leads to markedly increased expression of PTEN and reduced activity of the mTOR
      signalling pathway. These results suggest that the most probable pathomechanism
      underlying the microcephaly phenotype in this family involves downregulation of
      the mTOR pathway through overexpression of PTEN.

PMID- 30301740
TI  - Genome Instability Is Promoted by the Chromatin-Binding Protein Spn1 in
      Saccharomyces cerevisiae.
AB  - Cells expend a large amount of energy to maintain their DNA sequence. DNA repair
      pathways, cell cycle checkpoint activation, proofreading polymerases, and
      chromatin structure are ways in which the cell minimizes changes to the genome.
      During replication, the DNA-damage tolerance pathway allows the replication forks
      to bypass damage on the template strand. This avoids prolonged replication fork
      stalling, which can contribute to genome instability. The DNA-damage tolerance
      pathway includes two subpathways: translesion synthesis and template switch. Post
      translational modification of PCNA and the histone tails, cell cycle phase, and
      local DNA structure have all been shown to influence subpathway choice. Chromatin
      architecture contributes to maintaining genome stability by providing physical
      protection of the DNA and by regulating DNA-processing pathways. As such,
      chromatin-binding factors have been implicated in maintaining genome stability.
      Using Saccharomyces cerevisiae, we examined the role of Spn1 (Suppresses
      postrecruitment gene number 1), a chromatin-binding and transcription elongation
      factor, in DNA-damage tolerance. Expression of a mutant allele of SPN1 results in
      increased resistance to the DNA-damaging agent methyl methanesulfonate, lower
      spontaneous and damage-induced mutation rates, along with increased chronological
      life span. We attribute these effects to an increased usage of the template
      switch branch of the DNA-damage tolerance pathway in the spn1 strain. This
      provides evidence for a role of wild-type Spn1 in promoting genome instability,
      as well as having ties to overcoming replication stress and contributing to
      chronological aging.

PMID- 30301739
TI  - Radiation Exposure of Premature Infants Beyond the Perinatal Period.
AB  - OBJECTIVES: To determine the odds of premature compared with term infants
      exceeding the recommended radiation exposure threshold in the first year after
      discharge from birth hospitalization. METHODS: In this observational
      retrospective cohort study, we compared the radiation exposure of premature and
      term infants between 2008 and 2015 in an urban hospital system. The primary
      outcome was crossing the radiation exposure threshold of 1 millisievert. We
      assessed prematurity's effect on this outcome with multivariable logistic
      regression. RESULTS: In our study, 20 049 term and 2047 preterm infants met
      inclusion criteria. The population was approximately one-half female,
      predominantly multiracial or people of color (40% African American and 44%
      multiracial), and of low socioeconomic status. Premature infants had 2.25 times
      greater odds of crossing the threshold compared with term infants after
      adjustment for demographics (95% confidence interval [CI]: 1.66-3.05). Adjustment
      for complex chronic conditions, which are validated metrics of pediatric chronic
      illness, attenuated this association; however, premature infants still had 1.58
      times greater odds of crossing the threshold (95% CI: 1.16-2.15). When the final
      model was analyzed by degree of prematurity, very preterm and extremely preterm
      infants were significantly more likely to cross the threshold (1.85 [95% CI: 1.03
      3.32] and 2.53 [95% CI: 1.53-4.21], respectively), whereas late preterm infants
      were not (1.14 [95% CI: 0.73-1.78]). CONCLUSIONS: Premature infants crossed the
      recommended radiation threshold more often than term infants in the year after
      discharge from birth hospitalization.

PMID- 30301741
TI  - Improving youth mental health supports in Canada.

PMID- 30301742
TI  - Use of the emergency department as a first point of contact for mental health
      care by immigrant youth in Canada: a population-based study.
AB  - BACKGROUND: Emergency department visits as a first point of contact for people
      with mental illness may reflect poor access to timely outpatient mental health
      care. We sought to determine the extent to which immigrants use the emergency
      department as an entryway into mental health services. METHODS: We used linked
      health and demographic administrative data sets to design a population-based
      cohort study. We included youth (aged 10-24 yr) with an incident mental health
      emergency department visit from 2010 to 2014 in Ontario, Canada (n = 118 851).
      The main outcome measure was an emergency department visit for mental health
      reasons without prior mental health care from a physician on an outpatient basis.
      The main predictor of interest was immigrant status (refugee, non-refugee
      immigrant and non-immigrant). Immigrant-specific predictors included time since
      migration, and region and country of origin. We used Poisson models to estimate
      adjusted rate ratios (aRRs) and 95% confidence intervals (CIs). RESULTS: The
      cohort included 2194 (1.8%) refugee, 6680 (5.6%) non-refugee immigrant and 109
      977 (92.5%) nonimmigrant youth. Rates of first mental health contact in the
      emergency department were higher among refugee (61.3%) and non-refugee immigrant
      youth (57.6%) than non-immigrant youth (51.3%) (refugee aRR 1.17, 95% CI 1.13
      1.21; non-refugee immigrant aRR 1.10, 95% CI 1.08-1.13). Compared with non
      refugee immigrants, refugees had a higher rate of first mental health contact in
      the emergency department (aRR 1.06, 95% CI 1.02-1.11). We also observed higher
      rates among recent versus longer-term immigrants (aRR 1.10, 95% CI 1.05-1.16) and
      immigrants from Central America (aRR 1.17, 95% CI 1.08-1.26) and Africa (aRR
      1.15, 95% CI 1.06-1.24) versus from North America and Western Europe.
      INTERPRETATION: Immigrant youth are more likely to present with a first mental
      health crisis to the emergency department than non-immigrants, with variability
      by region of origin and time since migration. Immigrants may face barriers to
      access and use of outpatient mental health services from a physician. Efforts are
      needed to reduce stigma and identify mental health problems early, before crisis,
      among immigrant populations.

PMID- 30301744
TI  - Malnutrition in Canadian hospitals.

PMID- 30301745
TI  - Anterior and posterior segment vasculopathy associated with long-term use of
      tetrahydrozoline.

PMID- 30301746
TI  - Addressing bias and lack of objectivity in the Canadian resident matching
      process.

PMID- 30301747
TI  - Unintended consequences of focusing on accommodations and supports as barriers
      for medical trainees with disabilities.

PMID- 30301743
TI  - Canadian Cardiovascular Harmonized National Guidelines Endeavour (C-CHANGE)
      guideline for the prevention and management of cardiovascular disease in primary
      care: 2018 update.

PMID- 30301748
TI  - Are physicians too busy to ask about patients' concerns?

PMID- 30301749
TI  - Growing concern over medical students' excessive drinking.

PMID- 30301750
TI  - Do doctors experiencing burnout make more errors?

PMID- 30301751
TI  - David Oliver: Private GPs-a manufactured media scandal?

PMID- 30301752
TI  - Cross-sectional examination of extrapyramidal side effects in a specialist
      palliative care inpatient unit.
AB  - OBJECTIVES: Extrapyramidal side effects (EPSEs) are serious potentially
      reversible side effects of antipsychotic and other medications that can cause
      distress for patients. A core principle of palliative care involves optimising
      quality of life. If side effects of medications are burdensome, it is imperative
      that we address this issue. The aim of the study was to determine and describe
      the burden of EPSEs in a specialist inpatient unit. METHODS: Consenting patients
      who met inclusion criteria were assessed for EPSE with two validated screening
      tests, the Modified Simpson-Angus Scale (MSAS) and Barnes Akathisia Rating Scale
      (BARS). Additional demographic data were collected including medications
      associated with EPSE, previous history of EPSE and known risk factors that may
      predispose a patient to EPSE. RESULTS: 43% inpatients met inclusion criteria. At
      least 66% of patients were taking regular medications associated with EPSE. Of
      those, 25% were taking >=2 medications associated with EPSE. The MSAS revealed
      50% scored <3, 44% scored 3-5% and 6% scored 6-11. Seven patients had at least
      one 'not rateable score'. In the BARS (sitting+/-standing), 94% scored 0/5 and 6%
      scored 1/5. 12.5% of participants were able to stand for 2  min to complete the
      BARS. CONCLUSIONS: 50% screened positive for EPSE. The complete BARS was
      unsuitable for most participants. The MSAS, while allowing a not rateable score,
      may underestimate EPSE. The frailty of an inpatient unit population impacts on
      applicability of screening tools and may therefore underestimate the burden of
      the problem in this population. Development of a population-specific screening
      tool warrants further investigation.

PMID- 30301753
TI  - Palliative care clinicians and online education in India: a survey.
AB  - BACKGROUND: Whether online resources can facilitate spread of palliative care
      knowledge and skills in India is an urgent question given few providers and a
      large, ageing population. OBJECTIVES: We surveyed needs and feasibility regarding
      e-learning. METHODS: Indian, Australian and North American palliative care
      experts developed an electronic survey using Qualtrics, emailed to all
      registrants of the 2017 Indian Association of Palliative Care (IAPC) conference
      and distributed during the conference. RESULTS: Of 60 respondents (66% men, 60%
      doctors), most worked in hospitals and had oncology backgrounds, and 35% were
      from Kerala and Tamil Nadu. Most (90.9%) received palliative care training in
      India or overseas with 41% trained in a Trivandrum Institute of Palliative
      Sciences residential course (4-6 weeks). 17% completed the IAPC essential
      certificate and 22% had undertaken various distance learning courses. Interest in
      online training was substantial for most aspects of palliative care. CONCLUSION:
      There was a high level of interest and reported feasibility in taking a case
      based online course. This pilot survey provides support for online case-based
      education in India, particularly among physicians.

PMID- 30301755
TI  - Ipsilesional Motor Cortex Plasticity Participates in Spontaneous Hindlimb
      Recovery after Lateral Hemisection of the Thoracic Spinal Cord in the Rat.
AB  - After an incomplete spinal cord injury (SCI) spontaneous motor recovery can occur
      in mammals, but the underlying neural substrates remain poorly understood. The
      motor cortex is crucial for skilled motor learning and the voluntary control of
      movement and is known to reorganize after cortical injury to promote recovery.
      Motor cortex plasticity has also been shown to parallel the recovery of forelimb
      function after cervical SCI, but whether cortical plasticity participates in
      hindlimb recovery after SCI remains unresolved. Using intracortical
      microstimulation (ICMS) mapping, behavioral and cortical inactivation techniques
      in the female Long-Evans rat, we evaluated the spontaneous cortical mechanisms of
      hindlimb motor recovery 1-5 weeks after lateral hemisection of the thoracic (T8)
      spinal cord that ablated the crossed corticospinal tract (CST) from the
      contralesional motor cortex while sparing the majority of the CST from the
      ipsilesional motor cortex. Hemisection initially impaired hindlimb motor function
      bilaterally but significant recovery occurred during the first 3 weeks. ICMS
      revealed time-dependent changes in motor cortex organization, characterized by a
      chronic abolishment of hindlimb motor representation in the contralesional motor
      cortex and the development of transient bilateral hindlimb representation in the
      ipsilesional motor cortex 3 weeks after hemisection, when significant behavioral
      recovery occurred. Consistently, reversible inactivation of the ipsilesional, but
      not the contralesional motor cortex, during skilled ladder walking 3 weeks after
      hemisection reinstated deficits in both hindlimbs. These findings indicate that
      the ipsilesional motor cortex transiently reorganizes after lateral hemisection
      of the thoracic spinal cord to support recovery of hindlimb motor
      function.SIGNIFICANCE STATEMENT Partial motor recovery can occur after an
      incomplete spinal cord injury and is hypothesized to result from the
      reorganization of spared descending motor pathways. The motor cortex is crucial
      for the control of voluntary movement and contains topographical movement
      representations (motor maps) that are highly plastic. We examined the
      organization of hindlimb motor maps bilaterally after a lateral hemisection of
      the spinal cord to show that while motor maps are abolished in the deefferented
      cortex, the spared ipsilesional cortex transiently reorganizes to gain a
      representation of the affected hindlimb after injury that relates to recovery.
      This finding demonstrates that plasticity in the ipsilesional motor cortex at
      early time points after spinal cord hemisection is initially important to support
      motor recovery.

PMID- 30301754
TI  - Tropomodulin Isoform-Specific Regulation of Dendrite Development and Synapse
      Formation.
AB  - Neurons of the CNS elaborate highly branched dendritic arbors that host numerous
      dendritic spines, which serve as the postsynaptic platform for most excitatory
      synapses. The actin cytoskeleton plays an important role in dendrite development
      and spine formation, but the underlying mechanisms remain incompletely
      understood. Tropomodulins (Tmods) are a family of actin-binding proteins that cap
      the slow-growing (pointed) end of actin filaments, thereby regulating the
      stability, length, and architecture of complex actin networks in diverse cell
      types. Three members of the Tmod family, Tmod1, Tmod2, and Tmod3 are expressed in
      the vertebrate CNS, but their function in neuronal development is largely
      unknown. In this study, we present evidence that Tmod1 and Tmod2 exhibit distinct
      roles in regulating spine development and dendritic arborization, respectively.
      Using rat hippocampal tissues from both sexes, we find that Tmod1 and Tmod2 are
      expressed with distinct developmental profiles: Tmod2 is expressed early during
      hippocampal development, whereas Tmod1 expression coincides with synaptogenesis.
      We then show that knockdown of Tmod2, but not Tmod1, severely impairs dendritic
      branching. Both Tmod1 and Tmod2 are localized to a distinct subspine region where
      they regulate local F-actin stability. However, the knockdown of Tmod1, but not
      Tmod2, disrupts spine morphogenesis and impairs synapse formation. Collectively,
      these findings demonstrate that regulation of the actin cytoskeleton by different
      members of the Tmod family plays an important role in distinct aspects of
      dendrite and spine development.SIGNIFICANCE STATEMENT The Tropomodulin family of
      molecules is best known for controlling the length and stability of actin
      myofilaments in skeletal muscles. While several Tropomodulin members are
      expressed in the brain, fundamental knowledge about their role in neuronal
      function is limited. In this study, we show the unique expression profile and
      subcellular distribution of Tmod1 and Tmod2 in hippocampal neurons. While both
      Tmod1 and Tmod2 regulate F-actin stability, we find that they exhibit isoform
      specific roles in dendrite development and synapse formation: Tmod2 regulates
      dendritic arborization, whereas Tmod1 is required for spine development and
      synapse formation. These findings provide novel insight into the actin regulatory
      mechanisms underlying neuronal development, thereby shedding light on potential
      pathways disrupted in a number of neurological disorders.

PMID- 30301756
TI  - Insensitivity to Pain upon Adult-Onset Deletion of Nav1.7 or Its Blockade with
      Selective Inhibitors.
AB  - Strong human genetic evidence points to an essential contribution of the voltage
      gated sodium channel Nav1.7 to pain sensation: loss of Nav1.7 function leads to
      congenital insensitivity to pain, whereas gain-of-function mutations in the SCN9A
      gene that encodes Nav1.7 cause painful neuropathies, such as inherited
      erythromelalgia, a syndrome characterized by episodic spontaneous pain. Selective
      Nav1.7 channel blockers thus hold promise as potential painkillers with improved
      safety and reduced unwanted side effects compared with existing therapeutics. To
      determine the maximum effect of a theoretically perfectly selective Nav1.7
      inhibitor, we generated a tamoxifen-inducible KO mouse model enabling genetic
      deletion of Nav1.7 from adult mice. Electrophysiological recordings of sensory
      neurons from these mice following tamoxifen injection demonstrated the loss of
      Nav1.7 channel current and the resulting decrease in neuronal excitability of
      small-diameter neurons. We found that behavioral responses to most, but
      surprisingly not all, modalities of noxious stimulus are abolished following
      adult deletion of Nav1.7, pointing toward indications where Nav1.7 blockade
      should be efficacious. Furthermore, we demonstrate that isoform-selective
      acylsulfonamide Nav1.7 inhibitors show robust analgesic and antinociceptive
      activity acutely after a single dose in mouse pain models shown to be Nav1.7
      dependent. All experiments were done with both male and female mice.
      Collectively, these data expand the depth of knowledge surrounding Nav1.7 biology
      as it relates to pain, and provide preclinical proof of efficacy that lays a
      clear path toward translation for the therapeutic use of Nav1.7-selective
      inhibitors in humans.SIGNIFICANCE STATEMENT Loss-of-function mutations in the
      sodium channel Nav1.7 cause congenital insensitivity to pain in humans, making
      Nav1.7 a top target for novel pain drugs. Targeting Nav1.7 selectively has been
      challenging, however, in part due to uncertainties in which rodent pain models
      are dependent on Nav1.7. We have developed and characterized an adult-onset
      Nav1.7 KO mouse model that allows us to determine the expected effects of a
      theoretically perfect Nav1.7 blocker. Importantly, many commonly used pain
      models, such as mechanical allodynia after nerve injury, appear to not be
      dependent on Nav1.7 in the adult. By defining which models are Nav1.7 dependent,
      we demonstrate that selective Nav1.7 inhibitors can approximate the effects of
      genetic loss of function, which previously has not been directly established.

PMID- 30301757
TI  - A Multicomponent Neuronal Response Encodes the Larval Decision to Pupariate upon
      Amino Acid Starvation.
AB  - Organisms need to coordinate growth with development, particularly in the context
      of nutrient availability. Thus, multiple ways have evolved to survive extrinsic
      nutrient deprivation during development. In Drosophila, growth occurs during
      larval development. Larvae are thus critically dependent on nutritional inputs;
      but after critical weight, they pupariate even when starved. How nutrient
      availability is coupled to the internal metabolic state for the decision to
      pupariate needs better understanding. We had earlier identified glutamatergic
      interneurons in the ventral ganglion that regulate pupariation on a protein
      deficient diet. Here we report that Drosophila third instar larvae (either sex)
      sense arginine to evaluate their nutrient environment using an amino acid
      transporter Slimfast. The glutamatergic interneurons integrate external protein
      availability with internal metabolic state through neuropeptide signals. IP3
      mediated calcium release and store-operated calcium entry are essential in these
      glutamatergic neurons for such integration and alter neuronal function by
      reducing the expression of multiple ion channels.SIGNIFICANCE STATEMENT
      Coordinating growth with development, in the context of nutrient availability is
      a challenge for all organisms in nature. After attainment of "critical weight,"
      insect larvae can pupariate, even in the absence of nutrition. Mechanism(s) that
      stimulate appropriate cellular responses and allow normal development on a
      nutritionally deficient diet remain to be understood. Here, we demonstrate that
      nutritional deprivation, in postcritical weight larvae, is sensed by special
      sensory neurons through an amino acid transporter that detects loss of
      environmental arginine. This information is integrated by glutamatergic
      interneurons with the internal metabolic state through neuropeptide signals.
      These glutamatergic interneurons require calcium-signaling-regulated expression
      of a host of neuronal channels to generate complex calcium signals essential for
      pupariation on a protein-deficient diet.

PMID- 30301758
TI  - The Hippocampal Film Editor: Sensitivity and Specificity to Event Boundaries in
      Continuous Experience.
AB  - The function of the human hippocampus is normally investigated by experimental
      manipulation of discrete events. Less is known about what triggers hippocampal
      activity during more naturalistic, continuous experience. We hypothesized that
      the hippocampus would be sensitive to the occurrence of event boundaries, that
      is, moments in time identified by observers as a transition between events. To
      address this, we analyzed functional MRI data from two groups: one (n = 253, 131
      female) who viewed an 8.5 min film and another (n = 15, 6 female) who viewed a
      120 min film. We observed a strong hippocampal response at boundaries defined by
      independent observers, which was modulated by boundary salience (the number of
      observers that identified each boundary). In the longer film, there were
      sufficient boundaries to show that this modulation remained after covarying out a
      large number of perceptual factors. This hypothesis-driven approach was
      complemented by a data-driven approach, in which we identified hippocampal events
      as moments in time with the strongest hippocampal activity. The correspondence
      between these hippocampal events and event boundaries was highly significant,
      revealing that the hippocampal response is not only sensitive, but also specific
      to event boundaries. We conclude that event boundaries play a key role in shaping
      hippocampal activity during encoding of naturalistic events.SIGNIFICANCE
      STATEMENT Recent years have seen the field of human neuroscience research
      transitioning from experiments with simple stimuli to the study of more complex
      and naturalistic experience. Nonetheless, our understanding of the function of
      many brain regions, such as the hippocampus, is based primarily on the study of
      brief, discrete events. As a result, we know little of what triggers hippocampal
      activity in real-life settings when we are exposed to a continuous stream of
      information. When does the hippocampus "decide" to respond during the encoding of
      naturalistic experience? We reveal here that hippocampal activity measured by
      fMRI during film watching is both sensitive and specific to event boundaries,
      identifying a potential mechanism whereby event boundaries shape experience by
      modulation of hippocampal activity.

PMID- 30301760
TI  - Degranulation of gastrointestinal mast cells contributes to hepatic ischemia
      reperfusion injury in mice.
AB  - The pathological changes following liver damage, including those caused by
      ischemia and reperfusion (I/R), are closely related to gastrointestinal
      dysregulation. Mast cells (MCs) are tissue-resident immune cells abundant in the
      gastrointestinal system that play diverse roles. In view of the characteristic
      localization of MCs around the microvasculature, we hypothesized that a stimulus
      specific set of mediators released through degranulation of gastrointestinal MCs,
      which are enriched in hepatic sinusoids via the hepatic system, subsequently
      participate in associated pathological development within the liver. To elucidate
      the biological role of gastrointestinal MC granules in liver damage, we employed
      an experimental liver I/R model that allows conditional ablation of MCs. Marked
      degranulation was detected during I/R, which showed a significant positive
      correlation with liver damage. Our experiments further disclosed that MC
      degranulation primarily enhanced the cycle of inflammatory damage in I/R liver
      consisting of liver sinusoidal endothelial cell death, neutrophil infiltration,
      and formation of a neutrophil extracellular trap, with a concomitant increase in
      adhesion molecules, inflammatory cytokines, chemokines, and oxidative stress.
      Based on the collective results, we propose that suppression of activity or
      number of MCs may present an effective strategy for protection against hepatic
      I/R injury.

PMID- 30301759
TI  - Unilateral, 3D Arm Movement Kinematics Are Encoded in Ipsilateral Human Cortex.
AB  - There is increasing evidence that the hemisphere ipsilateral to a moving limb
      plays a role in planning and executing movements. However, the exact relationship
      between cortical activity and ipsilateral limb movements is uncertain. We sought
      to determine whether 3D arm movement kinematics (speed, velocity, and position)
      could be decoded from cortical signals recorded from the hemisphere ipsilateral
      to the moving limb. By having invasively monitored patients perform unilateral
      reaches with each arm, we also compared the encoding of contralateral and
      ipsilateral limb kinematics from a single cortical hemisphere. In four motor
      intact human patients (three male, one female) implanted with
      electrocorticography electrodes for localization of their epileptic foci, we
      decoded 3D movement kinematics of both arms with accuracies above chance.
      Surprisingly, the spatial and spectral encoding of contralateral and ipsilateral
      limb kinematics was similar, enabling cross-prediction of kinematics between
      arms. These results clarify our understanding that the ipsilateral hemisphere
      robustly contributes to motor execution and supports that the information of
      complex movements is more bihemispherically represented in humans than has been
      previously understood.SIGNIFICANCE STATEMENT Although limb movements are
      traditionally understood to be driven by the cortical hemisphere contralateral to
      a moving limb, movement-related neural activity has also been found in the
      ipsilateral hemisphere. This study provides the first demonstration that 3D arm
      movement kinematics can be decoded from human electrocorticographic signals
      ipsilateral to the moving limb. Surprisingly, the spatial and spectral encoding
      of contralateral and ipsilateral limb kinematics was similar. The finding that
      specific kinematics are encoded in the ipsilateral hemisphere demonstrates that
      the ipsilateral hemisphere contributes to the execution of unilateral limb
      movements, improving our understanding of motor control. Additionally, the
      bihemisheric representation of voluntary movements has implications for the
      development of neuroprosthetic systems for reaching and for neurorehabilitation
      strategies following cortical injuries.

PMID- 30301761
TI  - Novel treatment avenues for uterine leiomyoma: a new implication for endothelin?
AB  - Cysteine-rich angiogenic inducer 61 (CYR61), an angiogenic factor whose
      expression is decreased in fibroids. The aim of the present study was to
      determine if CYR61 secretion in smooth muscle cells (SMCs) is regulated by
      hypoxia and through the endothelin A (ETA) receptor. SMCs from fibroids (fSMC)
      and the adjacent myometrium smooth muscle cells (mSMCs) were extracted from ten
      women undergoing hysterectomy for uterine fibroids and cultured with or without
      1.0 uM of an ETA receptor antagonist for 24 h under either normal or hypoxic
      oxygen conditions. Cellular secretion of endothelin-1 (ET-1) and CYR61 were
      measured via enzyme linked immunosorbent assay in the cell culture media. SMCs
      were collected to determine cell proliferation and CYR61 protein expression via
      Western blot. ET-1 secretion was significantly increased in fSMC and was
      decreased with blockade of the ETA receptor under both normoxia (P=0.0004) and
      hypoxia (P=0.008). CYR61 expression was decreased in fSMCs and significantly
      increased with blockade of the ETA receptor under hypoxia (P=0.04). Cell
      proliferation decreased with ETA blockade under normoxia (P=0.0001) and hypoxia
      (P=0.001). These results suggest that suppression of CYR61 secretion in fSMC is
      regulated by the ET-1 and that blockade with ETA could be considered for a future
      treatment option.

PMID- 30301762
TI  - US opioids: Congress passes bill to tackle epidemic but provides little new
      funding.

PMID- 30301763
TI  - Sociodemographic correlates of eating disorder subtypes among men and women in
      France, with a focus on age.
AB  - BACKGROUND: On the population level, the association of age and other
      sociodemographic factors with eating disorders (ED) is unclear. METHODS: We used
      cross-sectional data from the French general population-based NutriNet-Sante e
      cohort (n=49 603 adults; 76.3% women; mean age=50.4+/-14.6 years). ED were
      evaluated in 2014 with the 5-item SCOFF screening questionnaire and the Expali
      algorithmic tool. Likely cases of restrictive, bulimic, hyperphagic and other ED
      were the dependent variables. Age, marital status, education, occupation,
      physical activity and smoking were the independent variables. Associations were
      estimated via gender-stratified multivariable polytomous logistic regression.
      RESULTS: Among women, age displayed inverse linear associations with both
      restrictive and bulimic ED, underscoring 18-25 years as the most vulnerable
      period (adjusted OR=3.37, 95% CI: 2.24 to 5.08 for restrictive ED; adjusted
      OR=2.98, 95% CI: 2.37 to 3.74 for bulimic ED, respectively). A similar
      association was observed in men regarding bulimic ED. In women, age was not
      associated with hyperphagic ED for which living alone, low education, low
      physical activity, being a homemaker/disabled/unemployed/retired, a manual worker
      or a former/current smoker had increased importance. In men, 18-39 years emerged
      as the least vulnerable period regarding hyperphagic ED (adjusted OR=0.74, 95%
      CI: 0.56 to 0.99). Across gender, having postsecondary education had significant
      inverse associations with all except restrictive ED, whereas being a student had
      a significant positive association with restrictive ED. CONCLUSIONS: The findings
      support gender-specific associations of age with four ED subtypes and could
      inform future prevention initiatives targeting specific ED among specific age
      groups. TRIAL REGISTRATION NUMBER: NCT03335644 ; Pre-results.

PMID- 30301764
TI  - Contrasted trends in health-related quality of life across gender, age categories
      and work status in France, 1995-2016: repeated population-based cross-sectional
      surveys using the SF-36.
AB  - BACKGROUND: Interest in monitoring health-related quality of life (HRQoL) in
      general populations has increased in the past 20 years, reinforced by population
      ageing and repeated economic crises. This study aims to identify temporal trends
      in HRQoL in France between 1995 and 2016 and to assess disparities according to
      demographic and socioeconomic characteristics. METHODS: Data from repeated
      population-based cross-sectional surveys conducted in 1995, 2003 and 2016 were
      used. HRQoL was measured using the Medical Outcomes Study 36-item Short Form (SF
      36) questionnaire. RESULTS: A substantial decrease in score was observed between
      1995 and 2016 for both genders in almost all subscales of the SF-36, with the
      largest decrease being in the mental health dimension for men. However, the age
      group 18-54 years were the most affected with persistent negative or even
      worsening trends in HRQoL. The largest decreases were among men aged 45-54 years
      and women aged 35-44 years in most dimensions, and among the age group 18-24
      years in vitality. Conversely, an overall improvement was noted among the age
      group 65-84 years. People in employment were more affected than the unemployed by
      the decline in several HRQoL dimensions. CONCLUSION: A general decline in HRQoL
      was found between 1995 and 2016 in the French population, but with wide
      disparities in trends between age groups. Young and especially middle-aged,
      employed people exhibited persistent negative and worsening trends. Consistent
      with evidence from traditional mental health morbidity and mortality indicators,
      our findings raise questions about the potential influence of macro-socioeconomic
      factors, especially the 2008 crisis; these observations deserve special attention
      from health policy-makers.

PMID- 30301766
TI  - Proliferating cell nuclear antigen interacts with the CRL4 ubiquitin ligase
      subunit CDT2 in DNA synthesis-induced degradation of CDT1.
AB  - During DNA replication or repair, the DNA polymerase cofactor, proliferating cell
      nuclear antigen (PCNA), homotrimerizes and encircles the replicating DNA, thereby
      acting as a DNA clamp that promotes DNA polymerase processivity. The formation of
      the PCNA trimer is also essential for targeting the replication- licensing
      protein, chromatin-licensing and DNA replication factor 1 (CDT1), for ubiquitin
      dependent proteolysis to prevent chromosomal DNA re-replication. CDT1 uses its
      PCNA-interacting peptide box (PIP box) to interact with PCNA, and the CRL4 E3
      ubiquitin ligase subunit CDT2 is recruited through the formation of PCNA-CDT1
      complexes. However, it remains unclear how CDT1 and many other PIP box-containing
      proteins are marked for degradation by the CRL4CDT2 ubiquitin ligase during DNA
      replication or damage. Here, using recombinant protein expression coupled with
      site-directed mutagenesis, we report that CDT2 and PCNA directly interact and
      this interaction depends on the presence of a highly conserved, C-terminal PIP
      box-like region in CDT2. Deletion or mutation of this region abolished the CDT2
      PCNA interaction between CDT2 and PCNA both in vitro and in vivo. Moreover, PCNA
      dependent CDT1 degradation in response to DNA damage and replication during the
      cell cycle requires an intact PIP box in CDT2. The requirement of the PIP boxes
      in both CDT2 and its substrate CDT1 suggests that the formation of the PCNA
      trimeric clamp around DNA during DNA replication and repair may bring together
      CDT1 and CRL4CDT2 ubiquitin E3 ligase to target CDT1 for proteolysis in a DNA
      synthesis-dependent manner.

PMID- 30301767
TI  - Three structurally and functionally distinct beta-glucuronidases from the human
      gut microbe Bacteroides uniformis.
AB  - The glycoside hydrolases encoded by the human gut microbiome play an integral
      role in processing a variety of exogenous and endogenous glycoconjugates. Here we
      present three structurally and functionally distinct beta-glucuronidase (GUS)
      glycoside hydrolases from a single human gut commensal microbe, Bacteroides
      uniformis We show using nine crystal structures, biochemical, and biophysical
      data that whereas these three proteins share similar overall folds, they exhibit
      different structural features that create three structurally and functionally
      unique enzyme active sites. Notably, quaternary structure plays an important role
      in creating distinct active site features that are hard to predict via structural
      modeling methods. The enzymes display differential processing capabilities toward
      glucuronic acid-containing polysaccharides and SN-38-glucuronide, a metabolite of
      the cancer drug irinotecan. We also demonstrate that GUS-specific and
      nonselective inhibitors exhibit varying potencies toward each enzyme. Together,
      these data highlight the diversity of GUS enzymes within a single Bacteroides gut
      commensal and advance our understanding of how structural details impact the
      specific roles microbial enzymes play in processing drug-glucuronide and glycan
      substrates.

PMID- 30301768
TI  - Inhibition of monoacylglycerol lipase, an anti-inflammatory and antifibrogenic
      strategy in the liver.
AB  - OBJECTIVE: Sustained inflammation originating from macrophages is a driving force
      of fibrosis progression and resolution. Monoacylglycerol lipase (MAGL) is the
      rate-limiting enzyme in the degradation of monoacylglycerols. It is a
      proinflammatory enzyme that metabolises 2-arachidonoylglycerol, an
      endocannabinoid receptor ligand, into arachidonic acid. Here, we investigated the
      impact of MAGL on inflammation and fibrosis during chronic liver injury. DESIGN:
      C57BL/6J mice and mice with global invalidation of MAGL (MAGL -/- ), or myeloid
      specific deletion of either MAGL (MAGLMye-/-), ATG5 (ATGMye-/-) or CB2 (CB2Mye-/
      ), were used. Fibrosis was induced by repeated carbon tetrachloride (CCl4)
      injections or bile duct ligation (BDL). Studies were performed on peritoneal or
      bone marrow-derived macrophages and Kupffer cells. RESULTS: MAGL -/- or MAGLMye-/
      mice exposed to CCl4 or subjected to BDL were more resistant to inflammation and
      fibrosis than wild-type counterparts. Therapeutic intervention with MJN110, an
      MAGL inhibitor, reduced hepatic macrophage number and inflammatory gene
      expression and slowed down fibrosis progression. MAGL inhibitors also accelerated
      fibrosis regression and increased Ly-6Clow macrophage number. Antifibrogenic
      effects exclusively relied on MAGL inhibition in macrophages, since MJN110
      treatment of MAGLMye-/- BDL mice did not further decrease liver fibrosis.
      Cultured macrophages exposed to MJN110 or from MAGLMye-/- mice displayed reduced
      cytokine secretion. These effects were independent of the cannabinoid receptor 2,
      as they were preserved in CB2Mye-/- mice. They relied on macrophage autophagy,
      since anti-inflammatory and antifibrogenic effects of MJN110 were lost in ATG5Mye
      /- BDL mice, and were associated with increased autophagic flux and autophagosome
      biosynthesis in macrophages when MAGL was pharmacologically or genetically
      inhibited. CONCLUSION: MAGL is an immunometabolic target in the liver. MAGL
      inhibitors may show promising antifibrogenic effects during chronic liver injury.

PMID- 30301769
TI  - Single LAMS versus multigate plastic stent drainage of WON; fair comparison or
      apples versus oranges?

PMID- 30301765
TI  - The Streptococcus pyogenes Shr protein captures human hemoglobin using two
      structurally unique binding domains.
AB  - In order to proliferate and mount an infection, many bacterial pathogens need to
      acquire iron from their host. The most abundant iron source in the body is the
      oxygen transporter hemoglobin (Hb). Streptococcus pyogenes, a potentially lethal
      human pathogen, uses the Shr protein to capture Hb on the cell surface. Shr is an
      important virulence factor, yet the mechanism by which it captures Hb and
      acquires its heme is not well-understood. Here, we show using NMR and biochemical
      methods that Shr binds Hb using two related modules that were previously defined
      as domains of unknown function (DUF1533). These hemoglobin-interacting domains
      (HIDs), called HID1 and HID2, are autonomously folded and independently bind Hb.
      The 1.5 A resolution crystal structure of HID2 revealed that it is a structurally
      unique Hb-binding domain. Mutagenesis studies revealed a conserved tyrosine in
      both HIDs that is essential for Hb binding. Our biochemical studies indicate that
      HID2 binds Hb with higher affinity than HID1 and that the Hb tetramer is engaged
      by two Shr receptors. NMR studies reveal the presence of a third autonomously
      folded domain between HID2 and a heme-binding NEAT1 domain, suggesting that this
      linker domain may position NEAT1 near Hb for heme capture.

PMID- 30301770
TI  - Rare cause of rectal stenosis in a patient with long-term use of Infliximab and
      Mercaptopurine for ulcerative colitis.
AB  - QUESTION: A 58-year-old, non-smoker male patient with no family history was
      followed up since 2002 for ulcerative colitis (UC) located in the rectosigmoid.
      He was initially treated by salicylates alone until November 2008. Mercaptopurine
      was started in August 2009 for steroid dependence with primary failure despite
      adequate 6 thioguanine nucleotides (6 TGN) level. He was included in February
      2010 in the PURSUIT trial testing Golimumab with only partial response. A
      combination therapy with Mercaptopurine and Infliximab was then started in
      December 2010 with a long-term clinical, biological and endoscopic steroid-free
      remission. A pan-chromoendoscopy performed in June 2016 showed a complete mucosal
      healing with no histological activity or dysplasia on multiple random biopsies.
      Regular monitoring of Infliximab trough levels and 6-TGN were appropriate. A
      rectosigmoidoscopy was carried in September 2017 for a relapse (figure 1A),
      scored UCEIS 3. Rectal biopsies showed a polymorphic inflammatory infiltrate with
      no dysplasia. Bacterial cultures were negative. A new Infliximab infusion was
      administered without clinical improvement. He was hospitalised in October 2017
      for poor general state, fever and persistent bloody diarrhoea. A CT scan of the
      chest, abdomen and pelvis found multiple mesenteric and peri-aortic
      lymphadenopathies, peritoneal infiltration with bilateral pyelocaliceal
      dilatation and major rectal thickening (figure 1B). The rectosigmoidoscopy
      revealed a stenosis from 5 to 20 cm from the anal verge passable by the
      fiberscope only (figure 1C). Biopsies were performed (figure 1D).gutjnl;gutjnl
      2018-317069v1/F1F1F1Figure 1(A) Endoscopic view of the rectosigmoid (27 September
      2017). (B) Abdominopelvic tomodensitometry: sagittal plane (17 October 2017). (C)
      Endoscopic view of the rectosigmoid (17 October 2017). (D) Anatomopathological
      examination of the biopsies performed. QUESTION: What is the diagnosis?

PMID- 30301771
TI  - Quantification of HBV core antibodies may help revisit infectious occult
      hepatitis B virus.

PMID- 30301772
TI  - Towards optimal pancreatic cyst fluid management: the need for standardisation.

PMID- 30301773
TI  - The Mitochondrial Endonuclease M20 Participates in the Down-regulation of
      Mitochondrial DNA in Pollen Cells.
AB  - Maintaining the appropriate number of mitochondrial DNA (mtDNA) molecules is
      crucial for supporting mitochondrial metabolism and function in both plant and
      animal cells. For example, a substantial decrease in mtDNA levels occurs as a key
      part of pollen development. The molecular mechanisms regulating mtDNA copy number
      are largely unclear, particularly with regard to those that reduce mtDNA levels.
      Here, we identified and purified a 20 kD endonuclease, M20, from maize (Zea mays)
      pollen mitochondria. We found M20 to be an H-N-H/N nuclease that degrades linear
      and circular DNA in the presence of Mg2+ or Mn2+. Arabidopsis thaliana AtM20,
      which shared high sequence similarity with maize M20, localized to the
      mitochondria, had a similar H-N-H/N structure, and degraded both linear and
      circular DNA. AtM20 transcript levels increased during pollen development, in
      parallel with a rapid reduction in mtDNA. Clustered regularly interspaced short
      palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing
      techniques were used to generate knockout lines of AtM20 (atm20), which exhibited
      a significant delay in the reduction in mtDNA levels in pollen vegetative cells
      but normal mtDNA levels in somatic cells. The delayed reduction in pollen mtDNA
      levels was rescued by the transgenic expression of AtM20 in atm20 plants. This
      study thus uncovers an endonucleolytic DNase in plant mitochondria and its
      crucial role in reducing mtDNA levels, pointing to the complex mechanism
      regulating mtDNA levels in plants.

PMID- 30301774
TI  - A Musashi Splice Variant and its Interaction Partners Influence Temperature
      Acclimation in Chlamydomonas.
AB  - Microalgae contribute significantly to carbon fixation on Earth. Global warming
      influences their physiology and growth rates. To understand algal short-term
      acclimation and adaptation to changes in ambient temperature, it is essential to
      identify and characterize the molecular components that sense small temperature
      changes, as well as the downstream signaling networks and physiological
      responses. Here, we used the green biflagellate alga Chlamydomonas reinhardtii as
      a model system to study responses to temperature. We report that an RNA
      recognition motif (RRM)-containing RNA-binding protein, Musashi, occurs in 25
      putative splice variants. These variants bear one, two, and three RRM domain(s),
      or even lack RRM domains. The most abundant Musashi variant, 12, with a molecular
      weight of 60 kDa, interacts with two clock-relevant members of RNA metabolism,
      the subunit C3 of the RNA-binding protein CHLAMY1 and the 5'-3' exoribonuclease
      XRN1. These proteins are able to integrate temperature information by up- or down
      regulation of their protein levels in cells grown at low (18{degree sign}C) or
      high (28{degree sign}C) temperature. We further show that the 60-kDa Musashi
      variants with three RRM-domains can bind to (UG)7-repeat containing RNAs and are
      up-regulated in cells grown at a higher temperature during early night.
      Intriguingly, the 60-kDa Musashi variant 12, as well as C3 and XRN1, confer
      thermal acclimation to C. reinhardtii, as shown with mutant lines. Our data
      suggest that these three proteins of the RNA metabolism machinery are key members
      of the thermal signaling network in C. reinhardtii.

PMID- 30301775
TI  - RNA Polymerase II read-through promotes expression of neighboring genes in SAL1
      PAP-XRN retrograde signaling.
AB  - In plants, the molecular function(s) of the nuclear localised 5'-3'
      EXORIBONUCLEASES (XRNs) are unclear; however, their activity is reported to have
      a significant effect on gene expression and SAL1-mediated retrograde signaling.
      Using Parallel Analysis of RNA Ends (PARE) we documented a dramatic increase in
      uncapped RNA substrates of the XRNs in both sal1 and xrn2xrn3 mutants. We found
      that a major consequence of reducing SAL1 or XRN activity was RNA Polymerase II
      (Pol II) 3' read-through. This occurred at 72% of expressed genes, demonstrating
      a major genome-wide role for the XRN-torpedo model of transcription termination
      in Arabidopsis. Read-through is speculated to have a negative effect on
      transcript abundance; however, we did not observe this. Rather, we identified a
      strong association between read-though and increased transcript abundance of
      tandemly orientated downstream genes, strongly correlated with the proximity
      (<1,000 bp) and expression of the upstream gene. We observed read-though in the
      proximity of 903 genes upregulated in the sal1-8 retrograde signaling mutant;
      thus, this phenomenon may directly account for up to 23% of genes upregulated in
      sal1-8. Using APX2 and AT5G43770 as exemplars, we genetically uncoupled read
      through loci from downstream genes to validate the principle of read-through
      mediated mRNA regulation, providing one mechanism by which an ostensibly post
      transcriptional exoribonuclease that targets uncapped RNAs could modulate gene
      expression.

PMID- 30301776
TI  - Polyploidy affects plant growth and alters cell wall composition.
AB  - Polyploidization has played a key role in plant breeding and crop improvement.
      Although its potential to increase biomass yield is well described, the effect of
      polyploidization on biomass composition has largely remained unexplored. Here, we
      generated a series of Arabidopsis (Arabidopsis thaliana) plants with different
      somatic ploidy levels (2n, 4n, 6n, and 8n) and performed rigorous phenotypic
      characterization. Kinematic analysis showed that polyploids developed slower
      compared to diploids; however, tetra- and hexaploids, but not octaploids,
      generated larger rosettes due to delayed flowering. In addition, morphometric
      analysis of leaves showed that polyploidy affected epidermal pavement cells, with
      increased cell size and reduced cell number per leaf blade with incrementing
      ploidy. However, the inflorescence stem dry weight was highest in tetraploids.
      Cell wall characterization revealed that the basic somatic ploidy level
      negatively correlated with lignin and cellulose content, and positively
      correlated with matrix polysaccharide content (i.e. hemicellulose and pectin) in
      the stem tissue. In addition, higher ploidy plants displayed altered sugar
      composition. Such effects were linked to the delayed development of polyploids.
      Moreover, the changes in polyploid cell wall composition promoted
      saccharification yield. The results of this study indicate that induction of
      polyploidy is a promising breeding strategy to further tailor crops for biomass
      production.

PMID- 30301777
TI  - Mesenchymal stem cell mechanotransduction is cAMP dependent and regulated by
      adenylyl cyclase 6 and the primary cilium.
AB  - Mechanical loading is a potent stimulus of bone adaptation, requiring the
      replenishment of the osteoblast from a progenitor population. One such progenitor
      is the mesenchymal stem cell (MSC), which undergoes osteogenic differentiation in
      response to oscillatory fluid shear. Yet, the mechanism mediating stem cell
      mechanotransduction, and thus the potential to target this therapeutically, is
      poorly understood. In this study, we demonstrate that MSCs utilise cAMP as a
      second messenger in mechanotransduction, which is required for flow-mediated
      increases in osteogenic gene expression. Furthermore, we demonstrate that this
      mechanosignalling is dependent on the primary cilium and the ciliary localised
      adenylyl cyclase 6. Finally, we also demonstrate that this mechanotransduction
      mechanism can be targeted therapeutically to enhance cAMP signalling and early
      osteogenic signalling, mimicking the beneficial effect of physical loading. Our
      findings therefore demonstrate a novel mechanism of MSC mechanotransduction that
      can be targeted therapeutically, demonstrating a potential mechanotherapeutic for
      bone-loss diseases such as osteoporosis.This article has an associated First
      Person interview with the first author of the paper.

PMID- 30301779
TI  - TM9SF4 levels determine sorting of transmembrane domains in the early secretory
      pathway.
AB  - Previous studies have shown that TM9SF4 interacts with glycine-rich transmembrane
      domains (TMDs) and promotes their surface localization, presumably by escorting
      them along the secretory pathway. Here, we delineated the role of TM9 proteins in
      the sorting of TMDs. Our results indicate that TM9SF4 interacts with and sorts a
      variety of TMDs. In human embryonic kidney (HEK) cells, a TMD carrying a
      positively charged residue (T-R1) or a negatively charged residue (T-D1) was
      localized to the endoplasmic reticulum (ER), but partially relocated to the Golgi
      complex upon overexpression of TM9SF4. These results show that TM9SF4 controls
      the sorting of TMDs at the ER-Golgi interface. Remarkably, sorting of T-R1 in
      HCT116 cells was different from that in HEK cells: in HCT116 cells, a substantial
      fraction of T-R1 was localized to the Golgi complex, and it was relocated to the
      ER by genetic ablation of TM9SF4. This observation indicates that TM9SF4 sorting
      activity differs in HEK and HCT116 cells, resulting in different sorting of TMDs
      in these two cell types. Although TM9SF1 associated with several TMDs, it did not
      visibly alter their intracellular transport in the secretory pathway and may
      function in other intracellular transport pathways.

PMID- 30301780
TI  - Mechanisms of integrin alphaVbeta5 clustering in flat clathrin lattices.
AB  - The family of integrin transmembrane receptors is essential for the normal
      function of multicellular organisms by facilitating cell-extracellular matrix
      adhesion. The vitronectin-binding integrin alphaVbeta5 localizes to focal
      adhesions (FAs) as well as poorly characterized flat clathrin lattices (FCLs).
      Here, we show that, in human keratinocytes, alphaVbeta5 is predominantly found in
      FCLs, and formation of the alphaVbeta5-containing FCLs requires the presence of
      vitronectin as ligand, Ca2+, and the clathrin adaptor proteins ARH (also known as
      LDLRAP1), Numb and EPS15/EPS15L1. Integrin chimeras, containing the extracellular
      and transmembrane domains of beta5 and the cytoplasmic domains of beta1 or beta3,
      almost exclusively localize in FAs. Interestingly, lowering actomyosin-mediated
      contractility promotes integrin redistribution to FLCs in an integrin tail
      dependent manner, while increasing cellular tension favors alphaVbeta5 clustering
      in FAs. Our findings strongly indicate that clustering of integrin alphaVbeta5 in
      FCLs is dictated by the beta5 subunit cytoplasmic domain, cellular tension and
      recruitment of specific adaptor proteins to the beta5 subunit cytoplasmic
      domains.

PMID- 30301778
TI  - Super-resolution imaging of live sperm reveals dynamic changes of the actin
      cytoskeleton during acrosomal exocytosis.
AB  - Filamentous actin (F-actin) is a key factor in exocytosis in many cell types. In
      mammalian sperm, acrosomal exocytosis (denoted the acrosome reaction or AR), a
      special type of controlled secretion, is regulated by multiple signaling pathways
      and the actin cytoskeleton. However, the dynamic changes of the actin
      cytoskeleton in live sperm are largely not understood. Here, we used the powerful
      properties of SiR-actin to examine actin dynamics in live mouse sperm at the
      onset of the AR. By using a combination of super-resolution microscopy techniques
      to image sperm loaded with SiR-actin or sperm from transgenic mice containing
      Lifeact-EGFP, six regions containing F-actin within the sperm head were revealed.
      The proportion of sperm possessing these structures changed upon capacitation. By
      performing live-cell imaging experiments, we report that dynamic changes of F
      actin during the AR occur in specific regions of the sperm head. While certain F
      actin regions undergo depolymerization prior to the initiation of the AR, others
      remain unaltered or are lost after exocytosis occurs. Our work emphasizes the
      utility of live-cell nanoscopy, which will undoubtedly impact the search for
      mechanisms that underlie basic sperm functions.This article has an associated
      First Person interview with the first author of the paper.

PMID- 30301781
TI  - Rab34 small GTPase is required for Hedgehog signaling and an early step of
      ciliary vesicle formation in mouse.
AB  - The primary cilium is a microtubule-based organelle that protrudes from the cell
      surface and plays essential roles in embryonic development. Ciliogenesis begins
      with the successive fusion of preciliary vesicles to form ciliary vesicles, which
      then dock onto the distal end of the mother centriole. Rab proteins have been
      linked to cilia formation in cultured cells, but not yet in vivo In the present
      study, we demonstrate that endocytic recycling protein Rab34 localizes to cilia,
      and that its mutation results in significant decrease of ciliogenesis in both
      cultured cells and mice. Rab34 is required for the successive fusion of
      preciliary vesicles to generate ciliary vesicles and for the migration of the
      mother centriole from perinuclear region to plasma membrane. We also show that
      Rab34 mutant mice exhibit polydactyly, and cleft-lip and -palate. These
      phenotypes are consistent with observations that nonciliated Rab34 mutant cells
      fail to respond to Hedgehog signaling and that processing of full-length Gli3 to
      its C-terminally truncated form is reduced in Rab34 mutant embryos. Therefore,
      Rab34 is required for an early step of ciliary vesicle formation and Hh signaling
      in vivo This article has an associated First Person interview with the first
      author of the paper.

PMID- 30301783
TI  - The RHEB-mTOR axis regulates expression of Tf2 transposons in fission yeast.
AB  - The human TSC2 gene, mutations in which predispose individuals to the disease
      tuberous sclerosis complex (TSC), encodes a GTPase-activating protein for the
      GTPase RHEB. Loss of TSC2 results in constitutive activation of RHEB and its
      target mammalian target of rapamycin (mTOR). We have previously reported that
      fission yeast (Schizosaccharomyces pombe) Tf2 retrotransposons (hereafter Tf2s)
      are abnormally induced upon nitrogen starvation in cells lacking the tsc2+ gene
      (Deltatsc2), a homolog of the human TSC2 gene, and in cells with a dominant
      active mutation in the fission yeast RHEB GTPase (rhb1-DA4). We report here that
      induction of Tf2s in these mutants is suppressed upon overexpression of the cgs2+
      gene, which encodes a cAMP-specific phosphodiesterase, or upon deletion of
      components in the glucose/cAMP signaling pathway, namely Cyr1, Pka1, Tor1 and the
      stress-activated transcription factor Atf1. The results suggest that the
      glucose/cAMP signaling pathway is downregulated when cells are starved for
      nitrogen. We also show that Tf2 proteins are degraded via autophagy, which is
      under control of Tor2, a homolog of human mTOR. It appears that failure in the
      two processes, downregulation of the glucose/cAMP signaling pathway and induction
      of autophagy, allows abnormal induction of Tf2s upon nitrogen starvation in
      Deltatsc2 and rhb1-DA4 cells.

PMID- 30301782
TI  - The AAA ATPase Afg1 preserves mitochondrial fidelity and cellular health by
      maintaining mitochondrial matrix proteostasis.
AB  - Mitochondrial functions are critical for cellular physiology; therefore, several
      conserved mechanisms are in place to maintain the functional integrity of
      mitochondria. However, many of the molecular details and components involved in
      ensuring mitochondrial fidelity remain obscure. Here, we identify a novel role
      for the conserved mitochondrial AAA ATPase Afg1 in mediating mitochondrial
      protein homeostasis during aging and in response to various cellular challenges.
      Saccharomyces cerevisiae cells lacking functional Afg1 are hypersensitive to
      oxidative insults, unable to tolerate protein misfolding in the matrix
      compartment and exhibit progressive mitochondrial failure as they age. Loss of
      the Afg1 ortholog LACE-1 in Caenorhabditis elegans is associated with reduced
      lifespan, impeded oxidative stress tolerance, impaired mitochondrial proteostasis
      in the motor neuron circuitry and altered behavioral plasticity. Our results
      indicate that Afg1 is a novel protein quality control factor, which plays an
      important evolutionarily conserved role in mitochondrial surveillance, and
      cellular and organismal health.

PMID- 30301785
TI  - Targeting neuro-immune communication in neurodegeneration: Challenges and
      opportunities.
AB  - Immune cells patrol the brain and can support its function, but can we modulate
      brain-immune communication to fight neurological diseases? Here, we briefly
      discuss the mechanisms orchestrating the cross-talk between the brain and the
      immune system and describe how targeting this interaction in a well-controlled
      manner could be developed as a universal therapeutic approach to treat
      neurodegeneration.

PMID- 30301784
TI  - Mitochondrial ultrastructural adaptations in fast muscles of mice lacking IL15RA.
AB  - The pro-inflammatory cytokine interleukin-15 (IL15) and its receptor alpha
      (IL15RA) participate in the regulation of musculoskeletal function and
      metabolism. Deletion of the Il15ra gene in mice increases spontaneous activity,
      improves fatigue resistance in the glycolytic extensor digitorum longus (EDL) and
      protects from diet-induced obesity. In humans, IL15RA single-nucleotide
      polymorphisms (SNPs) have been linked to muscle strength, metabolism and
      performance in elite endurance athletes. Taken together, these features suggest a
      possible role for IL15RA in muscle mitochondrial structure and function. Here, we
      have investigated the consequences of loss of IL15RA on skeletal muscle fiber
      type properties and mitochondrial ultrastructure. Immunostaining of the EDL for
      myosin heavy chain (MyHC) isoforms revealed no significant changes in fiber type.
      Electron microscopy (EM) analysis of the EDL indicated an overall higher
      mitochondria content, and increased cristae density in subsarcolemmal and A-band
      mitochondrial subpopulations. The higher cristae density in Il15ra -/-
      mitochondria was associated with higher OPA1 and cardiolipin levels. Overall,
      these data extend our understanding of the role of IL15RA signaling in muscle
      oxidative metabolism and adaptation to exercise.

PMID- 30301787
TI  - Preassembled GPCR signaling complexes mediate distinct cellular responses to
      ultralow ligand concentrations.
AB  - G protein-coupled receptors (GPCRs) are the largest class of cell surface
      signaling proteins, participate in nearly all physiological processes, and are
      the targets of 30% of marketed drugs. Typically, nanomolar to micromolar
      concentrations of ligand are used to activate GPCRs in experimental systems. We
      detected GPCR responses to a wide range of ligand concentrations, from attomolar
      to millimolar, by measuring GPCR-stimulated production of cyclic adenosine
      monophosphate (cAMP) with high spatial and temporal resolution. Mathematical
      modeling showed that femtomolar concentrations of ligand activated, on average,
      40% of the cells in a population provided that a cell was activated by one to two
      binding events. Furthermore, activation of the endogenous beta2-adrenergic
      receptor (beta2AR) and muscarinic acetylcholine M3 receptor (M3R) by femtomolar
      concentrations of ligand in cell lines and human cardiac fibroblasts caused
      sustained increases in nuclear translocation of extracellular signal-regulated
      kinase (ERK) and cytosolic protein kinase C (PKC) activity, respectively. These
      responses were spatially and temporally distinct from those that occurred in
      response to higher concentrations of ligand and resulted in a distinct cellular
      proteomic profile. This highly sensitive signaling depended on the GPCRs forming
      preassembled, higher-order signaling complexes at the plasma membrane.
      Recognizing that GPCRs respond to ultralow concentrations of neurotransmitters
      and hormones challenges established paradigms of drug action and provides a
      previously unappreciated aspect of GPCR activation that is quite distinct from
      that typically observed with higher ligand concentrations.

PMID- 30301786
TI  - The protein kinase p38alpha destabilizes p63 to limit epidermal stem cell
      frequency and tumorigenic potential.
AB  - The molecular circuitry directing tissue development and homeostasis is hardwired
      by genetic programs but may also be subject to fine-tuning or major modification
      by environmental conditions. It remains unclear whether such malleability is at
      work-particularly in tissues directly in contact with the environment-and
      contributes to their optimal maintenance and resilience. The protein kinase
      p38alpha is activated by physiological cues that signal tissue damage and
      neoplastic transformation. Here, we found that p38alpha phosphorylated and
      thereby destabilized p63, a transcription factor essential for epidermal
      development. Through this regulatory mechanism, p38alpha limited the frequency of
      keratinocytes with stem cell properties and tumorigenic potential.
      Correspondingly, epidermal loss of p38alpha expression or activity promoted or
      correlated with carcinogenesis in mouse and human skin, respectively. Genetic
      mouse models revealed a tumorigenic mechanism from p38alpha loss through p63
      mediated suppression of the matrix metalloprotease MMP13. These findings
      illustrate a previously uncharacterized epidermal tumor-suppressive mechanism in
      which stress-activated signaling induces the contraction of stem cell-like
      keratinocyte pools.

PMID- 30301789
TI  - Arid5a makes the IL-17A/F-responsive pathway less arid.
AB  - The cytokine interleukin-17A/F (IL-17A/F) not only protects the skin and mucosae
      against Candida albicans infection in mice and humans but also promotes
      autoimmunity and autoinflammation in mice. In this issue of Science Signaling,
      Amatya et al report that the RNA binding protein Arid5a promotes responses to IL
      17A/F through multiple mechanisms.

PMID- 30301788
TI  - IL-17 integrates multiple self-reinforcing, feed-forward mechanisms through the
      RNA binding protein Arid5a.
AB  - Interleukin-17A (IL-17A) not only stimulates immunity to fungal pathogens but
      also contributes to autoimmune pathology. IL-17 is only a modest activator of
      transcription in experimental tissue culture settings. However, IL-17 controls
      posttranscriptional events that enhance the expression of target mRNAs. Here, we
      showed that the RNA binding protein (RBP) Arid5a (AT-rich interactive domain
      containing protein 5a) integrated multiple IL-17-driven signaling pathways
      through posttranscriptional control of mRNA. IL-17 induced expression of Arid5a,
      which was recruited to the adaptor TRAF2. Arid5a stabilized IL-17-induced
      cytokine transcripts by binding to their 3' untranslated regions and also
      counteracted mRNA degradation mediated by the endoribonuclease MCPIP1 (Regnase
      1). Arid5a inducibly associated with the eukaryotic translation initiation
      complex and facilitated the translation of the transcription factors (TFs)
      IkappaBzeta (Nfkbiz ) and C/EBPbeta (Cebpb). These TFs in turn transactivated IL
      17-dependent promoters. Together, these data indicated that Arid5a orchestrates a
      feed-forward amplification loop, which promoted IL-17 signaling by controlling
      mRNA stability and translation.

PMID- 30301790
TI  - Neratinib is effective in breast tumors bearing both amplification and mutation
      of ERBB2 (HER2).
AB  - Mutations in ERBB2, the gene encoding epidermal growth factor receptor (EGFR)
      family member HER2, are common in and drive the growth of "HER2-negative" (not
      ERBB2 amplified) tumors but are rare in "HER2-positive" (ERBB2 amplified) breast
      cancer. We analyzed DNA-sequencing data from HER2-positive patients and used cell
      lines and a patient-derived xenograft model to test the consequence of HER2
      mutations on the efficacy of anti-HER2 agents such as trastuzumab, lapatinib, and
      neratinib, an irreversible pan-EGFR inhibitor. HER2 mutations were present in ~7%
      of HER2-positive tumors, all of which were metastatic but not all were previously
      treated. Compared to HER2 amplification alone, in both patients and cultured cell
      lines, the co-occurrence of HER2 mutation and amplification was associated with
      poor response to trastuzumab and lapatinib, the standard-of-care anti-HER2
      agents. In mice, xenografts established from a patient whose HER2-positive tumor
      acquired a D769Y mutation in HER2 after progression on trastuzumab-based therapy
      were resistant to trastuzumab or lapatinib but were sensitive to neratinib.
      Clinical data revealed that six heavily pretreated patients with tumors bearing
      coincident HER2 amplification and mutation subsequently exhibited a statistically
      significant response to neratinib monotherapy. Thus, these findings indicate that
      coincident HER2 mutation reduces the efficacy of therapies commonly used to treat
      HER2-positive breast cancer, particularly in metastatic and previously HER2
      inhibitor-treated patients, as well as potentially in patients scheduled for
      first-line treatment. Therefore, we propose that clinical studies testing the
      efficacy of neratinib are warranted selectively in breast cancer patients whose
      tumors carry both amplification and mutation of ERBB2/HER2.

PMID- 30301791
TI  - Identification of SLAC1 anion channel residues required for CO2/bicarbonate
      sensing and regulation of stomatal movements.
AB  - Increases in CO2 concentration in plant leaves due to respiration in the dark and
      the continuing atmospheric [CO2] rise cause closing of stomatal pores, thus
      affecting plant-water relations globally. However, the underlying CO2/bicarbonate
      (CO2/HCO3 -) sensing mechanisms remain unknown. [CO2] elevation in leaves
      triggers stomatal closure by anion efflux mediated via the SLAC1 anion channel
      localized in the plasma membrane of guard cells. Previous reconstitution analysis
      has suggested that intracellular bicarbonate ions might directly up-regulate
      SLAC1 channel activity. However, whether such a CO2/HCO3 - regulation of SLAC1 is
      relevant for CO2 control of stomatal movements in planta remains unknown. Here,
      we computationally probe for candidate bicarbonate-interacting sites within the
      SLAC1 anion channel via long-timescale Gaussian accelerated molecular dynamics
      (GaMD) simulations. Mutations of two putative bicarbonate-interacting residues,
      R256 and R321, impaired the enhancement of the SLAC1 anion channel activity by
      CO2/HCO3 - in Xenopus oocytes. Mutations of the neighboring charged amino acid
      K255 and residue R432 and the predicted gate residue F450 did not affect HCO3 -
      regulation of SLAC1. Notably, gas-exchange experiments with slac1-transformed
      plants expressing mutated SLAC1 proteins revealed that the SLAC1 residue R256 is
      required for CO2 regulation of stomatal movements in planta, but not for abscisic
      acid (ABA)-induced stomatal closing. Patch clamp analyses of guard cells show
      that activation of S-type anion channels by CO2/HCO3 -, but not by ABA, was
      impaired, indicating the relevance of R256 for CO2 signal transduction. Together,
      these analyses suggest that the SLAC1 anion channel is one of the physiologically
      relevant CO2/HCO3 - sensors in guard cells.

PMID- 30301793
TI  - Metastatic growth instructed by neutrophil-derived transferrin.
AB  - The tumor-promoting functions of neutrophils have been mainly attributed to
      induction of tumor angiogenesis or suppression of anticancer immunity. However, a
      direct impact of neutrophils on tumor cell growth and metastasis remains largely
      uncharacterized. Here, we coupled a proteomic approach with a functional screen
      to interrogate the secretome of tumor-associated neutrophils. Surprisingly, the
      iron-transporting protein transferrin was identified as the major mitogen for
      tumor cells secreted by neutrophils. Depletion of neutrophils inhibited lung
      metastasis and transferrin production in the metastatic microenvironment.
      Deletion of transferrin receptor suppressed growth of lung-colonizing tumor
      cells. Also, media conditioned by neutrophils isolated from metastatic breast
      cancer patients stimulated growth of human breast cancer cells, an effect that
      was largely abolished by transferrin immunodepletion. We identified GM-CSF, which
      is produced primarily by tumor cells, as a selective inducer of de novo
      transferrin synthesis in neutrophils through the Jak/Stat5beta pathway. GM-CSF
      neutralization or inhibition of Jak kinases curtailed neutrophil transferrin
      expression in vitro and in vivo as well as cancer metastasis. Thus, transferrin
      provides a mechanistic link between neutrophils and metastatic growth owing to
      the ability of tumor-infiltrating neutrophils to locally deliver this growth
      promoting protein in response to GM-CSF stimulation. Our study identifies
      neutrophil-derived transferrin as a key regulator of metastatic tumor cell growth
      and a therapeutic target for antimetastatic treatment.

PMID- 30301792
TI  - Protein shape modulates crowding effects.
AB  - Protein-protein interactions are usually studied in dilute buffered solutions
      with macromolecule concentrations of <10 g/L. In cells, however, the
      macromolecule concentration can exceed 300 g/L, resulting in nonspecific
      interactions between macromolecules. These interactions can be divided into hard
      core steric repulsions and "soft" chemical interactions. Here, we test a
      hypothesis from scaled particle theory; the influence of hard-core repulsions on
      a protein dimer depends on its shape. We tested the idea using a side-by-side
      dumbbell-shaped dimer and a domain-swapped ellipsoidal dimer. Both dimers are
      variants of the B1 domain of protein G and differ by only three residues. The
      results from the relatively inert synthetic polymer crowding molecules, Ficoll
      and PEG, support the hypothesis, indicating that the domain-swapped dimer is
      stabilized by hard-core repulsions while the side-by-side dimer shows little to
      no stabilization. We also show that protein cosolutes, which interact primarily
      through nonspecific chemical interactions, have the same small effect on both
      dimers. Our results suggest that the shape of the protein dimer determines the
      influence of hard-core repulsions, providing cells with a mechanism for
      regulating protein-protein interactions.

PMID- 30301794
TI  - Machine learning determination of atomic dynamics at grain boundaries.
AB  - In polycrystalline materials, grain boundaries are sites of enhanced atomic
      motion, but the complexity of the atomic structures within a grain boundary
      network makes it difficult to link the structure and atomic dynamics. Here, we
      use a machine learning technique to establish a connection between local
      structure and dynamics of these materials. Following previous work on bulk glassy
      materials, we define a purely structural quantity (softness) that captures the
      propensity of an atom to rearrange. This approach correctly identifies
      crystalline regions, stacking faults, and twin boundaries as having low
      likelihood of atomic rearrangements while finding a large variability within high
      energy grain boundaries. As has been found in glasses, the probability that atoms
      of a given softness will rearrange is nearly Arrhenius. This indicates a well
      defined energy barrier as well as a well-defined prefactor for the Arrhenius form
      for atoms of a given softness. The decrease in the prefactor for low-softness
      atoms indicates that variations in entropy exhibit a dominant influence on the
      atomic dynamics in grain boundaries.

PMID- 30301796
TI  - A potential solution for eliminating hypoxia as a cause for radioresistance.

PMID- 30301795
TI  - Characterizing posttranslational modifications in prokaryotic metabolism using a
      multiscale workflow.
AB  - Understanding the complex interactions of protein posttranslational modifications
      (PTMs) represents a major challenge in metabolic engineering, synthetic biology,
      and the biomedical sciences. Here, we present a workflow that integrates
      multiplex automated genome editing (MAGE), genome-scale metabolic modeling, and
      atomistic molecular dynamics to study the effects of PTMs on metabolic enzymes
      and microbial fitness. This workflow incorporates complementary approaches across
      scientific disciplines; provides molecular insight into how PTMs influence
      cellular fitness during nutrient shifts; and demonstrates how mechanistic details
      of PTMs can be explored at different biological scales. As a proof of concept, we
      present a global analysis of PTMs on enzymes in the metabolic network of
      Escherichia coli Based on our workflow results, we conduct a more detailed,
      mechanistic analysis of the PTMs in three proteins: enolase, serine
      hydroxymethyltransferase, and transaldolase. Application of this workflow
      identified the roles of specific PTMs in observed experimental phenomena and
      demonstrated how individual PTMs regulate enzymes, pathways, and, ultimately,
      cell phenotypes.

PMID- 30301797
TI  - Why large icosahedral viruses need scaffolding proteins.
AB  - While small single-stranded viral shells encapsidate their genome spontaneously,
      many large viruses, such as the herpes simplex virus or infectious bursal disease
      virus (IBDV), typically require a template, consisting of either scaffolding
      proteins or an inner core. Despite the proliferation of large viruses in nature,
      the mechanisms by which hundreds or thousands of proteins assemble to form
      structures with icosahedral order (IO) is completely unknown. Using continuum
      elasticity theory, we study the growth of large viral shells (capsids) and show
      that a nonspecific template not only selects the radius of the capsid, but also
      leads to the error-free assembly of protein subunits into capsids with universal
      IO. We prove that as a spherical cap grows, there is a deep potential well at the
      locations of disclinations that later in the assembly process will become the
      vertices of an icosahedron. Furthermore, we introduce a minimal model and
      simulate the assembly of a viral shell around a template under nonequilibrium
      conditions and find a perfect match between the results of continuum elasticity
      theory and the numerical simulations. Besides explaining available experimental
      results, we provide a number of predictions. Implications for other problems in
      spherical crystals are also discussed.

PMID- 30301798
TI  - Nonproteinogenic deep mutational scanning of linear and cyclic peptides.
AB  - High-resolution structure-activity analysis of polypeptides requires amino acid
      structures that are not present in the universal genetic code. Examination of
      peptide and protein interactions with this resolution has been limited by the
      need to individually synthesize and test peptides containing nonproteinogenic
      amino acids. We describe a method to scan entire peptide sequences with multiple
      nonproteinogenic amino acids and, in parallel, determine the thermodynamics of
      binding to a partner protein. By coupling genetic code reprogramming to deep
      mutational scanning, any number of amino acids can be exhaustively substituted
      into peptides, and single experiments can return all free energy changes of
      binding. We validate this approach by scanning two model protein-binding peptides
      with 21 diverse nonproteinogenic amino acids. Dense structure-activity maps were
      produced at the resolution of single aliphatic atom insertions and deletions.
      This permits rapid interrogation of interaction interfaces, as well as
      optimization of affinity, fine-tuning of physical properties, and systematic
      assessment of nonproteinogenic amino acids in binding and folding.

PMID- 30301799
TI  - Human leukemia mutations corrupt but do not abrogate GATA-2 function.
AB  - By inducing the generation and function of hematopoietic stem and progenitor
      cells, the master regulator of hematopoiesis GATA-2 controls the production of
      all blood cell types. Heterozygous GATA2 mutations cause immunodeficiency,
      myelodysplastic syndrome, and acute myeloid leukemia. GATA2 disease mutations
      commonly disrupt amino acid residues that mediate DNA binding or cis-elements
      within a vital GATA2 intronic enhancer, suggesting a haploinsufficiency mechanism
      of pathogenesis. Mutations also occur in GATA2 coding regions distinct from the
      DNA-binding carboxyl-terminal zinc finger (C-finger), including the amino
      terminal zinc finger (N-finger), and N-finger function is not established.
      Whether distinct mutations differentially impact GATA-2 mechanisms is unknown.
      Here, we demonstrate that N-finger mutations decreased GATA-2 chromatin occupancy
      and attenuated target gene regulation. We developed a genetic complementation
      assay to quantify GATA-2 function in myeloid progenitor cells from Gata2 -77
      enhancer-mutant mice. GATA-2 complementation increased erythroid and myeloid
      differentiation. While GATA-2 disease mutants were not competent to induce
      erythroid differentiation of Lin-Kit+ myeloid progenitors, unexpectedly, they
      promoted myeloid differentiation and proliferation. As the myelopoiesis-promoting
      activity of GATA-2 mutants exceeded that of GATA-2, GATA2 disease mutations are
      not strictly inhibitory. Thus, we propose that the haploinsufficiency paradigm
      does not fully explain GATA-2-linked pathogenesis, and an amalgamation of
      qualitative and quantitative defects instigated by GATA2 mutations underlies the
      complex phenotypes of GATA-2-dependent pathologies.

PMID- 30301800
TI  - C-type lectin receptor LSECtin-mediated apoptotic cell clearance by macrophages
      directs intestinal repair in experimental colitis.
AB  - Epithelial barrier disruption is a major cause of inflammatory bowel disease
      (IBD); however, the cellular and molecular regulation of intestinal epithelial
      homeostasis remains largely undefined. Here, we show that the C-type lectin
      receptor LSECtin (Clec4g) on macrophages is required for protection against
      dextran sulfate sodium-induced colitis. Mechanistically, LSECtin promotes
      apoptotic cell clearance by macrophages and induces the production of
      antiinflammatory/tissue repair factors in an engulfment-dependent manner, which
      in turn stimulates epithelial cell proliferation. Deletion of LSECtin results in
      defective engulfment by colon macrophages, leading to aberrant proresolving
      factor production and impaired intestinal epithelium repair. Collectively, our
      findings suggest that LSECtin-dependent corpse clearance by macrophages can
      direct intestinal regeneration and maintenance of the mucosal barrier after
      injury.

PMID- 30301802
TI  - MmpL8MAB controls Mycobacterium abscessus virulence and production of a
      previously unknown glycolipid family.
AB  - Mycobacterium abscessus is a peculiar rapid-growing Mycobacterium (RGM) capable
      of surviving within eukaryotic cells thanks to an arsenal of virulence genes also
      found in slow-growing mycobacteria (SGM), such as Mycobacterium tuberculosis A
      screen based on the intracellular survival in amoebae and macrophages (MPhi) of
      an M. abscessus transposon mutant library revealed the important role of
      MAB_0855, a yet uncharacterized Mycobacterial membrane protein Large (MmpL).
      Large-scale comparisons with SGM and RGM genomes uncovered MmpL12 proteins as
      putative orthologs of MAB_0855 and a locus-scale synteny between the MAB_0855 and
      Mycobacterium chelonae mmpL8 loci. A KO mutant of the MAB_0855 gene, designated
      herein as mmpL8 MAB , had impaired adhesion to MPhi and displayed a decreased
      intracellular viability. Despite retaining the ability to block phagosomal
      acidification, like the WT strain, the mmpL8 MAB mutant was delayed in damaging
      the phagosomal membrane and in making contact with the cytosol. Virulence
      attenuation of the mutant was confirmed in vivo by impaired zebrafish killing and
      a diminished propensity to induce granuloma formation. The previously shown role
      of MmpL in lipid transport prompted us to investigate the potential lipid
      substrates of MmpL8MAB Systematic lipid analysis revealed that MmpL8MAB was
      required for the proper expression of a glycolipid entity, a glycosyl diacylated
      nonadecyl diol (GDND) alcohol comprising different combinations of oleic and
      stearic acids. This study shows the importance of MmpL8MAB in modifying
      interactions between the bacteria and phagocytic cells and in the production of a
      previously unknown glycolipid family.

PMID- 30301801
TI  - Activity-dependent bulk endocytosis proteome reveals a key presynaptic role for
      the monomeric GTPase Rab11.
AB  - Activity-dependent bulk endocytosis (ADBE) is the dominant mode of synaptic
      vesicle endocytosis during high-frequency stimulation, suggesting it should play
      key roles in neurotransmission during periods of intense neuronal activity.
      However, efforts in elucidating the physiological role of ADBE have been hampered
      by the lack of identified molecules which are unique to this endocytosis mode. To
      address this, we performed proteomic analysis on purified bulk endosomes, which
      are a key organelle in ADBE. Bulk endosomes were enriched via two independent
      approaches, a classical subcellular fractionation method and isolation via
      magnetic nanoparticles. There was a 77% overlap in proteins identified via the
      two protocols, and these molecules formed the ADBE core proteome. Bioinformatic
      analysis revealed a strong enrichment in cell adhesion and cytoskeletal and
      signaling molecules, in addition to expected synaptic and trafficking proteins.
      Network analysis identified Rab GTPases as a central hub within the ADBE
      proteome. Subsequent investigation of a subset of these Rabs revealed that Rab11
      both facilitated ADBE and accelerated clathrin-mediated endocytosis. These
      findings suggest that the ADBE proteome will provide a rich resource for the
      future study of presynaptic function, and identify Rab11 as a regulator of
      presynaptic function.

PMID- 30301804
TI  - Translating biased signaling in the ghrelin receptor system into differential in
      vivo functions.
AB  - Biased signaling has been suggested as a means of selectively modulating a
      limited fraction of the signaling pathways for G-protein-coupled receptor family
      members. Hence, biased ligands may allow modulation of only the desired
      physiological functions and not elicit undesired effects associated with
      pharmacological treatments. The ghrelin receptor is a highly sought antiobesity
      target, since the gut hormone ghrelin in humans has been shown to increase both
      food intake and fat accumulation. However, it also modulates mood, behavior,
      growth hormone secretion, and gastric motility. Thus, blocking all pathways of
      this receptor may give rise to potential side effects. In the present study, we
      describe a highly promiscuous signaling capacity for the ghrelin receptor. We
      tested selected ligands for their ability to regulate the various pathways
      engaged by the receptor. Among those, a biased ligand, YIL781, was found to
      activate the Galphaq/11 and Galpha12 pathways selectively without affecting the
      engagement of beta-arrestin or other G proteins. YIL781 was further characterized
      for its in vivo physiological functions. In combination with the use of mice in
      which Galphaq/11 was selectively deleted in the appetite-regulating AgRP neurons,
      this biased ligand allowed us to demonstrate that selective blockade of
      Galphaq/11, without antagonism at beta-arrestin or other G-protein coupling is
      sufficient to decrease food intake.

PMID- 30301803
TI  - Meiosis-specific recombinase Dmc1 is a potent inhibitor of the Srs2
      antirecombinase.
AB  - Cross-over recombination products are a hallmark of meiosis because they are
      necessary for accurate chromosome segregation and they also allow for increased
      genetic diversity during sexual reproduction. However, cross-overs can also cause
      gross chromosomal rearrangements and are therefore normally down-regulated during
      mitotic growth. The mechanisms that enhance cross-over product formation upon
      entry into meiosis remain poorly understood. In Saccharomyces cerevisiae, the
      Superfamily 1 (Sf1) helicase Srs2, which is an ATP hydrolysis-dependent motor
      protein that actively dismantles recombination intermediates, promotes synthesis
      dependent strand annealing, the result of which is a reduction in cross-over
      recombination products. Here, we show that the meiosis-specific recombinase Dmc1
      is a potent inhibitor of Srs2. Biochemical and single-molecule assays demonstrate
      that Dmc1 acts by inhibiting Srs2 ATP hydrolysis activity, which prevents the
      motor protein from undergoing ATP hydrolysis-dependent translocation on Dmc1
      bound recombination intermediates. We propose a model in which Dmc1 helps
      contribute to cross-over formation during meiosis by antagonizing the
      antirecombinase activity of Srs2.

PMID- 30301805
TI  - Chronic social stress-induced hyperglycemia in mice couples individual stress
      susceptibility to impaired spatial memory.
AB  - Stringent glucose demands render the brain susceptible to disturbances in the
      supply of this main source of energy, and chronic stress may constitute such a
      disruption. However, whether stress-associated cognitive impairments may arise
      from disturbed glucose regulation remains unclear. Here we show that chronic
      social defeat (CSD) stress in adult male mice induces hyperglycemia and directly
      affects spatial memory performance. Stressed mice developed hyperglycemia and
      impaired glucose metabolism peripherally as well as in the brain (demonstrated by
      PET and induced metabolic bioluminescence imaging), which was accompanied by
      hippocampus-related spatial memory impairments. Importantly, the cognitive and
      metabolic phenotype pertained to a subset of stressed mice and could be linked to
      early hyperglycemia 2 days post-CSD. Based on this criterion, ~40% of the
      stressed mice had a high-glucose (glucose >150 mg/dL), stress-susceptible
      phenotype. The relevance of this biomarker emerges from the effects of the
      glucose-lowering sodium glucose cotransporter 2 inhibitor empagliflozin, because
      upon dietary treatment, mice identified as having high glucose demonstrated
      restored spatial memory and normalized glucose metabolism. Conversely, reducing
      glucose levels by empagliflozin in mice that did not display stress-induced
      hyperglycemia (resilient mice) impaired their default-intact spatial memory
      performance. We conclude that hyperglycemia developing early after chronic stress
      threatens long-term glucose homeostasis and causes spatial memory dysfunction.
      Our findings may explain the comorbidity between stress-related and metabolic
      disorders, such as depression and diabetes, and suggest that cognitive
      impairments in both types of disorders could originate from excessive cerebral
      glucose accumulation.

PMID- 30301807
TI  - Redox-dependent niche differentiation provides evidence for multiple bacterial
      sources of glycerol tetraether lipids in lakes.
AB  - Terrestrial paleoclimate archives such as lake sediments are essential for our
      understanding of the continental climate system and for the modeling of future
      climate scenarios. However, quantitative proxies for the determination of
      paleotemperatures are sparse. The relative abundances of certain bacterial
      lipids, i.e., branched glycerol dialkyl glycerol tetraethers (brGDGTs), respond
      to changes in environmental temperature, and thus have great potential for
      climate reconstruction. Their application to lake deposits, however, is hampered
      by the lack of fundamental knowledge on the ecology of brGDGT-producing microbes
      in lakes. Here, we show that brGDGTs are synthesized by multiple groups of
      bacteria thriving under contrasting redox regimes in a deep meromictic Swiss lake
      (Lake Lugano). This niche partitioning is evidenced by highly distinct brGDGT
      inventories in oxic vs. anoxic water masses, and corresponding vertical patterns
      in bacterial 16S rRNA gene abundances, implying that sedimentary brGDGT records
      are affected by temperature-independent changes in the community composition of
      their microbial producers. Furthermore, the stable carbon isotope composition
      (delta13C) of brGDGTs in Lake Lugano and 34 other (peri-)Alpine lakes attests to
      the widespread heterotrophic incorporation of 13C-depleted, methane-derived
      biomass at the redox transition zone of mesotrophic to eutrophic lake systems.
      The brGDGTs produced under such hypoxic/methanotrophic conditions reflect near
      bottom water temperatures, and are characterized by comparatively low delta13C
      values. Depending on climate zone and water depth, lake sediment archives
      predominated by deeper water/low-13C brGDGTs may provide more reliable records of
      climate variability than those where brGDGTs derive from terrestrial and/or
      aquatic sources with distinct temperature imprints.

PMID- 30301806
TI  - Molecular mechanism of activation of the immunoregulatory amidase NAAA.
AB  - Palmitoylethanolamide is a bioactive lipid that strongly alleviates pain and
      inflammation in animal models and in humans. Its signaling activity is terminated
      through degradation by N-acylethanolamine acid amidase (NAAA), a cysteine
      hydrolase expressed at high levels in immune cells. Pharmacological inhibitors of
      NAAA activity exert profound analgesic and antiinflammatory effects in rodent
      models, pointing to this protein as a potential target for therapeutic drug
      discovery. To facilitate these efforts and to better understand the molecular
      mechanism of action of NAAA, we determined crystal structures of this enzyme in
      various activation states and in complex with several ligands, including both a
      covalent and a reversible inhibitor. Self-proteolysis exposes the otherwise
      buried active site of NAAA to allow catalysis. Formation of a stable substrate-
      or inhibitor-binding site appears to be conformationally coupled to the
      interaction of a pair of hydrophobic helices in the enzyme with lipid membranes,
      resulting in the creation of a linear hydrophobic cavity near the active site
      that accommodates the ligand's acyl chain.

PMID- 30301808
TI  - Human mitochondrial degradosome prevents harmful mitochondrial R loops and
      mitochondrial genome instability.
AB  - R loops are nucleic acid structures comprising an DNA-RNA hybrid and a displaced
      single-stranded DNA. These structures may occur transiently during transcription,
      playing essential biological functions. However, persistent R loops may become
      pathological as they are important drivers of genome instability and have been
      associated with human diseases. The mitochondrial degradosome is a functionally
      conserved complex from bacteria to human mitochondria. It is composed of the ATP
      dependent RNA and DNA helicase SUV3 and the PNPase ribonuclease, playing a
      central role in mitochondrial RNA surveillance and degradation. Here we describe
      a new role for the mitochondrial degradosome in preventing the accumulation of
      pathological R loops in the mitochondrial DNA, in addition to preventing dsRNA
      accumulation. Our data indicate that, similar to the molecular mechanisms acting
      in the nucleus, RNA surveillance mechanisms in the mitochondria are crucial to
      maintain its genome integrity by counteracting pathological R-loop accumulation.

PMID- 30301810
TI  - Highly disordered histone H1-DNA model complexes and their condensates.
AB  - Disordered proteins play an essential role in a wide variety of biological
      processes, and are often posttranslationally modified. One such protein is
      histone H1; its highly disordered C-terminal tail (CH1) condenses
      internucleosomal linker DNA in chromatin in a way that is still poorly
      understood. Moreover, CH1 is phosphorylated in a cell cycle-dependent manner that
      correlates with changes in the chromatin condensation level. Here we present a
      model system that recapitulates key aspects of the in vivo process, and also
      allows a detailed structural and biophysical analysis of the stages before and
      after condensation. CH1 remains disordered in the DNA-bound state, despite its
      nanomolar affinity. Phase-separated droplets (coacervates) form, containing
      higher-order assemblies of CH1/DNA complexes. Phosphorylation at three serine
      residues, spaced along the length of the tail, has little effect on the local
      properties of the condensate. However, it dramatically alters higher-order
      structure in the coacervate and reduces partitioning to the coacervate phase.
      These observations show that disordered proteins can bind tightly to DNA without
      a disorder-to-order transition. Importantly, they also provide mechanistic
      insights into how higher-order structures can be exquisitely sensitive to
      perturbation by posttranslational modifications, thus broadening the repertoire
      of mechanisms that might regulate chromatin and other macromolecular assemblies.

PMID- 30301809
TI  - mTOR inhibitors lower an intrinsic barrier to virus infection mediated by IFITM3.
AB  - Rapamycin and its derivatives are specific inhibitors of mammalian target of
      rapamycin (mTOR) kinase and, as a result, are well-established immunosuppressants
      and antitumorigenic agents. Additionally, this class of drug promotes gene
      delivery by facilitating lentiviral vector entry into cells, revealing its
      potential to improve gene therapy efforts. However, the precise mechanism was
      unknown. Here, we report that mTOR inhibitor treatment results in down-regulation
      of the IFN-induced transmembrane (IFITM) proteins. IFITM proteins, especially
      IFITM3, are potent inhibitors of virus-cell fusion and are broadly active against
      a range of pathogenic viruses. We found that the effect of rapamycin treatment on
      lentiviral transduction is diminished upon IFITM silencing or knockout in primary
      and transformed cells, and the extent of transduction enhancement depends on
      basal expression of IFITM proteins, with a major contribution from IFITM3. The
      effect of rapamycin treatment on IFITM3 manifests at the level of protein, but
      not mRNA, and is selective, as many other endosome-associated transmembrane
      proteins are unaffected. Rapamycin-mediated degradation of IFITM3 requires
      endosomal trafficking, ubiquitination, endosomal sorting complex required for
      transport (ESCRT) machinery, and lysosomal acidification. Since IFITM proteins
      exhibit broad antiviral activity, we show that mTOR inhibition also promotes
      infection by another IFITM-sensitive virus, Influenza A virus, but not infection
      by Sendai virus, which is IFITM-resistant. Our results identify the molecular
      basis by which mTOR inhibitors enhance virus entry into cells and reveal a
      previously unrecognized immunosuppressive feature of these clinically important
      drugs. In addition, this study uncovers a functional convergence between the mTOR
      pathway and IFITM proteins at endolysosomal membranes.

PMID- 30301813
TI  - Reproductive outsourcing: an empirical ethics account of cross-border
      reproductive care in Canada.
AB  - Cross-border reproductive care (CBRC) can be defined as the movement from one
      jurisdiction to another for medically assisted reproduction (MAR). CBRC raises
      many ethical concerns that have been addressed extensively. However, the
      conclusions are still based on scarce evidence even considering the global scale
      of CBRC. Empirical ethics appears as a way to foster this ethical reflection on
      CBRC while attuning it with the experiences of its main actors. To better
      understand the 'in and out' situation of CBRC in Canada, we conducted an
      ethnographic study taking a 'critically applied ethics' approach. This article
      presents a part of the findings of this research, obtained by data triangulation
      from qualitative analysis of pertinent literature, participant observation in two
      Canadian fertility clinics and 40 semidirected interviews. Based on participants'
      perceptions, four themes emerged: (1) inconsistencies of the Canadian legal
      framework; (2) autonomy and the necessity to resort to CBRC; (3) safety and the
      management of CBRC individual risks; and (4) justice and solidarity. The
      interaction between these four themes highlights the problematic of 'reproductive
      outsourcing' that characterised the Canadian situation, a system where the
      controversial aspects of MAR are knowingly pushed outside the borders.

PMID- 30301811
TI  - Combined inhibition of receptor tyrosine and p21-activated kinases as a
      therapeutic strategy in childhood ALL.
AB  - Receptor tyrosine kinase (RTK)-dependent signaling has been implicated in the
      pathogenesis of acute lymphoblastic leukemia (ALL) of childhood. However, the RTK
      dependent signaling state and its interpretation with regard to biological
      behavior are often elusive. To decipher signaling circuits that link RTK activity
      with biological output in vivo, we established patient-derived xenograft ALL (PDX
      ALL) models with dependencies on fms-like tyrosine kinase 3 (FLT3) and platelet
      derived growth factor receptor beta (PDGFRB), which were interrogated by
      phosphoproteomics using iTRAQ mass spectrometry. Signaling circuits were
      determined by receptor type and cellular context with few generic features, among
      which we identified group I p21-activated kinases (PAKs) as potential therapeutic
      targets. Growth factor stimulation markedly increased catalytic activities of
      PAK1 and PAK2. RNA interference (RNAi)-mediated or pharmacological inhibition of
      PAKs using allosteric or adenosine triphosphate (ATP)-competitive compounds
      attenuated cell growth and increased apoptosis in vitro. Notably, PAK1- or PAK2
      directed RNAi enhanced the antiproliferative effects of the type III RTK and
      protein kinase C inhibitor midostaurin. Treatment of FLT3- or PDGFRB-dependent
      ALLs with ATP-competitive PAK inhibitors markedly decreased catalytic activities
      of both PAK isoforms. In FLT3-driven ALL, this effect was augmented by
      coadministration of midostaurin resulting in synergistic effects on growth
      inhibition and apoptosis. Finally, combined treatment of FLT3 D835H PDX-ALL with
      the ATP-competitive group I PAK inhibitor FRAX486 and midostaurin in vivo
      significantly prolonged leukemia progression-free survival compared with
      midostaurin monotherapy or control. Our study establishes PAKs as potential
      downstream targets in RTK-dependent ALL of childhood, the inhibition of which
      might help prevent the selection or acquisition of resistance mutations toward
      tyrosine kinase inhibitors.

PMID- 30301812
TI  - Accelerated, but not conventional, radiotherapy of murine B-cell lymphoma induces
      potent T cell-mediated remissions.
AB  - Conventional local tumor irradiation (LTI), delivered in small daily doses over
      several weeks, is used clinically as a palliative, rather than curative,
      treatment for chemotherapy-resistant diffuse large B-cell lymphoma (DLBCL) for
      patients who are ineligible for hematopoietic cell transplantation. Our goal was
      to test the hypothesis that accelerated, but not conventional, LTI would be more
      curative by inducing T cell-mediated durable remissions. We irradiated
      subcutaneous A20 and BL3750 lymphoma tumors in mice with a clinically relevant
      total radiation dose of 30 Gy LTI, delivered in 10 doses of 3 Gy over 4 days
      (accelerated irradiation) or as 10 doses of 3 Gy over 12 days (conventional
      irradiation). Compared with conventional LTI, accelerated LTI resulted in more
      complete and durable tumor remissions. The majority of these mice were resistant
      to rechallenge with lymphoma cells, demonstrating the induction of memory
      antitumor immunity. The increased efficacy of accelerated LTI correlated with
      higher levels of tumor cell necrosis vs apoptosis and expression of "immunogenic
      cell death" markers, including calreticulin, heat shock protein 70 (Hsp70), and
      Hsp90. Accelerated LTI-induced remissions were not seen in immunodeficient Rag-2 
      /- mice, CD8+ T-cell-depleted mice, or Batf-3 -/- mice lacking CD8alpha+ and
      CD103+ dendritic cells. Accelerated, but not conventional, LTI in immunocompetent
      hosts induced marked increases in tumor-infiltrating CD4+ and CD8+ T cells and
      MHCII+CD103+CD11c+ dendritic cells and corresponding reductions in exhausted PD
      1+Eomes+CD8+ T cells and CD4+CD25+FOXP3+ regulatory T cells. These findings raise
      the possibility that accelerated LTI can provide effective immune control of
      human DLBCL.

PMID- 30301814
TI  - The rebirth of medical paternalism: An NHS Trust v Y.
AB  - Over the last quarter of a century, English medical law has taken an increasingly
      firm stand against medical paternalism. This is exemplified by cases such as
      Bolitho v City and Hackney Health Authority, Chester v Afshar, and Montgomery v
      Lanarkshire Health Board. In relation to decision-making on behalf of
      incapacitous adults, the actuating principle of the Mental Capacity Act 2005 is
      respect for patient autonomy. The only lawful acts in relation to an incapacitous
      person are acts which are in the best interests of that person. The 2005 Act
      requires a holistic assessment of best interests. Best interests are wider than
      'medical best interests'. The 2018 judgment of the Supreme Court in An NHS Trust
      v Y (which concerned the question of whether a court needed to authorise the
      withdrawal of life-sustaining clinically administered nutrition/hydration (CANH)
      from patients in prolonged disorders of consciousness (PDOC)) risks reviving
      medical paternalism. The judgment, in its uncritical endorsement of guidelines
      from various medical organisations, may lend inappropriate authority to medical
      judgments of best interests and silence or render impotent non-medical
      contributions to the debate about best interests-so frustrating the 2005 Act. To
      minimise these dangers, a system of meditation should be instituted whenever it
      is proposed to withdraw (at least) life-sustaining CANH from (at least) patients
      with PDOC, and there needs to be a guarantee of access to the courts for
      families, carers and others who wish to challenge medical conclusions about
      withdrawal. This would entail proper public funding for such challenges.

PMID- 30301815
TI  - Sixty seconds on . . . Emma's Diary.

PMID- 30301816
TI  - Making MOC Quality Improvement Participation Meaningful.

PMID- 30301817
TI  - Pediatricians' Participation in Quality Improvement at the Time of Enrollment in
      MOC.
AB  - BACKGROUND AND OBJECTIVES: Although national bodies have proclaimed the
      importance of incorporating quality improvement (QI) into the daily fabric of
      clinical care, the actual proportion of practicing pediatricians who participate
      in QI activities on an annual basis is unknown. Correspondingly little is known
      about pediatrician motivations for, attitudes about, and support received for QI
      participation. METHODS: Pediatric diplomates enrolling in the American Board of
      Pediatrics' Maintenance of Certification program during calendar year 2016 were
      provided with the opportunity to complete a brief survey. A portion of the survey
      was focused on issues related to participation in QI programs. RESULTS: Survey
      responses were received from 8714 of the 11 890 diplomates who enrolled in
      Maintenance of Certification in 2016 (response rate: 73.3%). Overall, 86.6% of
      respondents reported participation in at least 1 QI project in the previous year.
      There was variation in previous-year participation in a QI project by practice
      affiliation categories, ranging from 79.9% for nonacademic generalists to 92.4%
      for academic specialists. The extrinsic requirement for QI to maintain board
      certification was the dominant motivator among all respondents (50.7%), followed
      by 2 intrinsic factors: identify gaps in practice and implement change (40.3%)
      and opportunity to collaborate with others (36.9%). CONCLUSIONS: Although the
      results are encouraging, despite almost 2 decades of national attention to the
      quality of health care and efforts to embed continual QI in health care delivery
      activities, ~1 in 5 nonacademic pediatricians and 1 in 10 academic pediatricians
      did not report participating in any QI activities in the previous year.

PMID- 30301818
TI  - Incidence of primary graft dysfunction after lung transplantation is altered by
      timing of allograft implantation.
AB  - The importance of circadian factors in managing patients is poorly understood. We
      present two retrospective cohort studies showing that lungs reperfused between 4
      and 8 AM have a higher incidence (OR 1.12; 95% CI 1.03 to 1.21; p=0.01) of
      primary graft dysfunction (PGD) in the first 72 hours after transplantation.
      Cooling of the donor lung, occurring during organ preservation, shifts the donor
      circadian clock causing desynchrony with the recipient. The clock protein REV
      ERBalpha directly regulates PGD biomarkers explaining this circadian regulation
      while also allowing them to be manipulated with synthetic REV-ERB ligands.

PMID- 30301819
TI  - Gaps in the evidence for treatment decisions in cystic fibrosis: a systematic
      review.
AB  - INTRODUCTION: Cystic fibrosis (CF) is a multisystem disorder. Treatment is
      complex and evidence for treatment decisions may be absent. Characterising gaps
      in the research evidence will highlight treatment uncertainties and help
      prioritise research questions. We systematically identified the evidence gaps for
      treatment decisions in CF. METHODS: We searched for systematic reviews and
      guidelines on treatment interventions in CF. Two researchers identified eligible
      reviews with arbitration from a third. Using a structured framework, we extracted
      and characterised evidence gaps. RESULTS: There were 73 reviews and 21 guidelines
      that met our inclusion criteria. From these, we identified 148 evidence gaps
      across a range of treatment areas. We found 111 evidence gaps through systematic
      reviews and a further 37 from guidelines. The reason for an evidence gap could
      only be reliably characterised for systematic reviews. In most cases, there was
      more than one explanation-most commonly few or no trials (97/111 evidence gaps).
      Other important factors leading to evidence gaps were small sample size (49/111),
      inadequate duration of follow-up (38/111) or intervention (37/111) and factors
      relating to outcomes (35/111). Evidence gaps from both systematic reviews and
      guidelines fell into the following categories: Respiratory (91); Gastrointestinal
      (20); PhysiotherapyandExercise (16); Musculoskeletal (6); Endocrine (4); Basic
      defect of CF (8); Psychosocial (2); Ears, Nose and Throat (1). CONCLUSIONS: We
      have compiled an up-to-date list of treatment uncertainties in CF and the reasons
      for these uncertainties. These can be used as a resource to aid researchers and
      funders when planning future trials. PROSPERO REGISTRATION NUMBER: Pre-results;
      CRD42015030111.

PMID- 30301820
TI  - Coeliac disease in children.

PMID- 30301821
TI  - Angling-induced injuries have a negative impact on suction feeding performance
      and hydrodynamics in marine shiner perch, Cymatogaster aggregata.
AB  - Fishing is a popular and lucrative sport around the world and, in some cases, may
      contribute to declining fish stocks. To mediate this problem and maintain fish
      biomass in aquatic ecosystems, catch-and-release fishing, whereby a fish is
      caught and immediately released, has been implemented in many countries. It is
      unclear whether the injuries to the mouth that are caused by the hook have an
      impact on feeding performance of fishes. Using high-speed video and computational
      fluid dynamics (CFD), we asked whether injuries around the mouth caused by
      fishing hooks have a negative impact on suction feeding performance (measured as
      maximum prey velocity) of the commonly angled marine shiner perch (Cymatogaster
      aggregata). We hypothesized that fish with mouth injuries would exhibit decreased
      feeding performance compared with controls. Ten shiner perch were caught using
      scientific angling and 10 were caught using a seine net. Feeding events were then
      recorded at 500 frames per second using a high-speed camera. Compared with the
      control group, maximum prey velocity was significantly lower in the injured group
      (P<0.01). Maximum gape, time to peak gape, maximum jaw protrusion and predator
      prey distance were comparable between the control and injured groups, leading us
      to conclude that the injury-induced hole in the buccal cavity wall reduced the
      pressure gradient during mouth expansion, thereby reducing the velocity of water
      entering the fish's mouth. This was confirmed with our CFD modelling. Fishing
      injuries in nature are likely to depress feeding performance of fish after they
      have been released, although it is currently unclear whether this has a
      significant impact on survival.

PMID- 30301822
TI  - Therapeutic use of intermittent fasting for people with type 2 diabetes as an
      alternative to insulin.
AB  - This case series documents three patients referred to the Intensive Dietary
      Management clinic in Toronto, Canada, for insulin-dependent type 2 diabetes. It
      demonstrates the effectiveness of therapeutic fasting to reverse their insulin
      resistance, resulting in cessation of insulin therapy while maintaining control
      of their blood sugars. In addition, these patients were also able to lose
      significant amounts of body weight, reduce their waist circumference and also
      reduce their glycated haemoglobin level.

PMID- 30301823
TI  - Twenty years of research on attention-deficit/hyperactivity disorder (ADHD):
      looking back, looking forward.
AB  - In this clinical review we summarise what in our view have been some the most
      important advances in the past two decades, in terms of diagnostic definition,
      epidemiology, genetics and environmental causes, neuroimaging/cognition and
      treatment of attention-deficit/hyperactivity disorder (ADHD), including: (1) the
      most recent changes to the diagnostic criteria in the Diagnostic and Statistical
      Manual of Mental Disorders and International Classification of Diseases; (2) meta
      analytic evidence showing that, after accounting for diagnostic methods, the
      rates of ADHD are fairly consistent across Western countries; (3) the recent
      finding of the first genome-wide significant risk loci for ADHD; (4) the paradigm
      shift in the pathophysiological conceptualisation of ADHD from alterations in
      individual brain regions to a complex dysfunction in brain networks; (5) evidence
      supporting the short-term efficacy of ADHD pharmacological treatments, with a
      different profile of efficacy and tolerability in children/adolescents versus
      adults; (6) a series of meta-analyses showing that, while non-pharmacological
      treatment may not be effective to target ADHD core symptoms, some of them
      effectively address ADHD-related impairments (such as oppositional behaviours for
      parent training and working memory deficits for cognitive training). We also
      discuss key priorities for future research in each of these areas of
      investigation. Overall, while many research questions have been answered, many
      others need to be addressed. Strengthening multidisciplinary collaborations,
      relying on large data sets in the spirit of Open Science and supporting research
      in less advantaged countries will be key to face the challenges ahead.

PMID- 30301824
TI  - Inflammation and psychopathology in children following PICU admission: an
      exploratory study.
AB  - BACKGROUND: Survivors of critical illness in childhood commonly display
      subsequent psychiatric symptoms including emotional and behavioural difficulties,
      and manifestations of post-traumatic stress disorder (PTSD). Anomalies in
      inflammatory profiles are an established finding in these childhood psychiatric
      conditions. OBJECTIVE: This exploratory study aimed to investigate whether
      abnormal peripheral blood inflammatory markers measured during paediatric
      intensive care unit (PICU) admission were associated with psychiatric symptoms
      after discharge. METHODS: We performed a prospective observational cohort study
      on 71 children with septic illness, meningoencephalitis and other critical
      disorders admitted to two PICUs between 2007 and 2010. 3-6 months following
      discharge, subjects were assessed for global psychiatric risk (ie, presence of
      emotional and behavioural difficulties on the parental Strengths and Difficulties
      Questionnaire (SDQ)), and for PTSD risk using the child-rated Impact of Events
      Scale (IES-8). Inflammatory and related biological markers were transcribed from
      PICU admission notes (white cell count, lymphocytes, neutrophils, C reactive
      protein (CRP), platelets, fibrinogen and lactate). FINDINGS: Global psychiatric
      risk at follow-up was associated with abnormal lymphocyte count during admission
      (chi2=6.757, p=0.014, n=48). In children with sepsis, partial correlation
      analyses controlling for age and gender highlighted associations between (i) SDQ
      scores and low lymphocyte count (r=-0.712; p=0.009, n=14), and (ii) IES-8 score
      and high CRP levels (r=0.823; p=0.006, n=11). These associations remained after
      correction for multiple comparisons. CONCLUSION: These results support the
      hypothesis that acute inflammation may play a role in determining the development
      of psychopathology following PICU admission. CLINICAL IMPLICATIONS: If the
      findings are replicated, they may help to better highlight which children are at
      risk of post-PICU psychopathology and appropriately target follow-up.

PMID- 30301826
TI  - Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real
      Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models.
AB  - Purpose: The inability to intraoperatively distinguish primary tumor, as well as
      lymphatic spread, increases the probability of positive surgical margins, tumor
      recurrence, and surgical toxicity. The goal of this study was to develop a tumor
      specific optical probe for real-time fluorescence-guided surgery.Experimental
      Design: A humanized antibody fragment against PSCA (A11 minibody, A11 Mb) was
      conjugated with a near-infrared fluorophore, IRDye800CW. The integrity and
      binding of the probe to PSCA were confirmed by gel electrophoresis, size
      exclusion chromatography, and flow cytometry, respectively. The ability of the
      probe to detect tumor-infiltrated lymph nodes and metastatic lesions was
      evaluated in 2 xenograft models, as well as in transgenic mice expressing human
      PSCA (hPSCA). An invasive intramuscular model was utilized to evaluate the
      efficacy of the A11 Mb-IRDye800CW-guided surgery.Results: A11 Mb was successfully
      conjugated with IRDye800CW and retained specific binding to PSCA. In vivo imaging
      showed maximal signal-to-background ratios at 48 hours. The A11 Mb-IRDye800CW
      specifically detected PSCA-positive primary tumors, tumor-infiltrated lymph
      nodes, and distant metastases with high contrast. Fluorescence guidance
      facilitated more complete tumor resection, reduced tumor recurrence, and improved
      overall survival, compared with conventional white light surgery. The probe
      successfully identified primary orthotopic tumors and metastatic lesions in hPSCA
      transgenic mice.Conclusions: Real-time fluorescence image-guided surgery with A11
      Mb-IRDye800CW enabled detection of lymph node metastases and positive surgical
      margins, facilitated more complete tumor removal, and improved survival, compared
      with white light surgery. These results may be translatable into clinical
      practice to improve surgical and patient outcomes. Clin Cancer Res; 1-13. (c)2018
      AACR.

PMID- 30301825
TI  - Intertumoral Heterogeneity of CD3+ and CD8+ T-Cell Densities in the
      Microenvironment of DNA Mismatch-Repair-Deficient Colon Cancers: Implications for
      Prognosis.
AB  - Background: Colorectal cancers with deficient DNA mismatch repair (dMMR) are
      presumed to uniformly have dense lymphocytic infiltration that underlies their
      favorable prognosis and is critical to their responsiveness to immunotherapy, as
      compared with MMR-proficient (pMMR) tumors. We examined T-cell densities and
      their potential heterogeneity in a large cohort of dMMR tumors.Experimental
      Design: CD3+ and CD8+ T-cell densities were quantified at the invasive margin
      (IM) and tumor core (CT) in 561 stage III colon cancers (dMMR, n = 278; pMMR, n =
      283) from a phase III adjuvant trial (N0147). Their association with overall
      survival (OS) was determined using multivariable Cox analysis.Results: Although
      CD3+ and CD8+ T-cell densities in the tumor microenvironment were higher in dMMR
      versus pMMR tumors overall, intertumoral heterogeneity in densities between
      tumors was significantly higher by 30% to 88% among dMMR versus pMMR cancers (P <
      0.0001 for all four T-cell subtypes [CD3+IM, CD3+CT, CD8+IM, CD8+CT]). A
      substantial proportion of dMMR tumors (26% to 35% depending on the T-cell
      subtype) exhibited T-cell densities as low as that in the bottom half of pMMR
      tumors. All four T-cell subtypes were prognostic in dMMR with CD3+IM being the
      most strongly prognostic. Low (vs. high) CD3+IM was independently associated with
      poorer OS among dMMR (HR, 4.76; 95% confidence interval, 1.43-15.87; P = 0.0019)
      and pMMR tumors (P = 0.0103).Conclusions: Tumor-infiltrating T-cell densities
      exhibited greater intertumoral heterogeneity among dMMR than pMMR colon cancers,
      with CD3+IM providing robust stratification of both dMMR and pMMR tumors for
      prognosis. Potentially, lower T-cell densities among dMMR tumors may contribute
      to immunotherapy resistance. Clin Cancer Res; 1-9. (c)2018 AACR.

PMID- 30301827
TI  - Transcription Factor Myeloid Zinc-Finger 1 Suppresses Human Gastric
      Carcinogenesis by Interacting with Metallothionein 2A.
AB  - PURPOSE: Metallothionein 2A (MT2A) suppresses the progression of human gastric
      cancer (GC) potentially through an "MT2A-NF-kappaB pathway" with unclear
      mechanisms. This study explored the role of a transcription factor, myeloid zinc
      finger 1 (MZF1), in MT2A-NF-kappaB pathway and its clinical significance in GC.
      EXPERIMENTAL DESIGN: MZF1 expression and function in GC were investigated in
      vitro and in vivo. The relationship between MZF1 and MT2A was determined by gain-
      and loss-of-function assays in GC cells and an immortalized gastric cell line GES
      1. The prognostic value of MZF1 expression in association with MT2A was evaluated
      using immunohistochemistry in two cohorts. RESULTS: MZF1 was epigenetically
      silenced in human GC cell lines and primary tumors. Overexpression of MZF1 in GC
      cells suppressed cell proliferation and migration, as well as the growth of
      xenograft tumors in nude mice. Knocking-down of MZF1 transformed GES-1 cells into
      a malignant phenotype characterized by increased cell growth and migration.
      Mechanistically, MZF1 was upregulated in both GC and GES-1 cells by MT2A
      ectopically expressed or induced upon treatment with a garlic-derived compound,
      diallyl trisulfide (DATS). MZF1 associated with MT2A was co-localized in the
      nuclei of GES-1 cells to target the promoter of NFKB inhibitor alpha (NFKBIA).
      Clinically, MT2A and MZF1 were progressively downregulated in clinical specimens
      undergoing gastric malignant transformation. Downregulation of MT2A and MZF1 was
      significantly correlated with poorer patient prognosis. CONCLUSIONS: MT2A exerts
      its anti-GC effects by complexing with MZF1 to target NFKBIA. MT2A/MZF1 may serve
      as valuable prognostic markers and novel therapeutic targets for human GC.

PMID- 30301828
TI  - Telomerase Activation and ATRX Mutations Are Independent Risk Factors for
      Metastatic Pheochromocytoma and Paraganglioma.
AB  - Purpose: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine
      tumors. Whereas most PPGLs are benign, up to 20% may become metastatic with SDHB-
      and FH-mutated tumors showing the higher risk. We aimed at determining the
      contribution of immortalization mechanisms to metastatic progression.Experimental
      Design: Immortalization mechanisms were investigated in 200 tumors. To identify
      telomerase (+) tumors, we analyzed genomic alterations leading to transcriptional
      activation of TERT comprising promoter mutations, hypermethylation and gain copy
      number. To identify tumors that activated the alternative lengthening of telomere
      (ALT) mechanism, we combined analyses of telomere length by slot blot, telomere
      heterogeneity by telomere FISH, and ATRX mutations by next-generation sequencing.
      Univariate/multivariate and metastasis-free survival (MFS) and overall survival
      (OS) analyses were carried out for assessment of risk factors and clinical
      outcomes.Results: Only 37 of 200 (18.5%) tumors achieved immortalization.
      Telomerase activation occurred in 12 metastatic tumors and was prevalent in SDHB
      mutated paragangliomas (P = 2.42e-09). ALT features were present in 25 tumors,
      mostly pheochromocytomas, regardless of metastatic status or molecular group (P =
      0.169), yet ATRX mutations were found preferentially in SDHB/FH-mutated
      metastatic tumors (P = 0.0014). Telomerase activation and ATRX mutations were
      independent factors of poor prognosis: MFS (hazard ratio, 48.2 and 33.1; P =
      6.50E-07 and 1.90E-07, respectively); OS (hazard ratio, 97.4 and 44.1; P = 4.30E
      03 and 2.00E-03, respectively) and were associated with worse MFS and OS (log
      rank tests P < 0.0001).Conclusions: Assessment of telomerase activation and ATRX
      mutations could be used to identify metastatic PPGLs, particularly in tumors at
      high risk of progression. Clin Cancer Res; 1-11. (c)2018 AACR.

PMID- 30301829
TI  - Expression of AR-V7 and ARv567es in circulating tumor cells correlates with
      outcomes to taxane therapy in men with metastatic prostate cancer treated in
      TAXYNERGY.
AB  - PURPOSE: Biomarkers aiding treatment optimization in metastatic castration
      resistant prostate cancer (mCRPC) are scarce. Presence or absence of androgen
      receptor (AR) splice variants, AR-V7 and ARv567es, in mCRPC patient circulating
      tumor cells (CTCs) may be associated with taxane treatment outcomes. METHODS: A
      novel digital droplet PCR (ddPCR) assay assessed AR splice variant expression in
      patient CTCs receiving docetaxel or cabazitaxel in TAXYNERGY (NCT01718353).
      Outcomes were examined according to AR splice variant expression, including
      prostate-specific antigen (PSA)50 response and progression-free survival (PFS).
      RESULTS: Of 54 evaluable patients, 36 (67%) were AR-V7+, 42 (78%) ARv567es+, 29
      (54%) double positive and 5 (9%) double negative. PSA50 response rates at any
      time were numerically higher for AR-V7- vs AR-V7+ (78% vs 58%; p=0.23) and for
      ARv567es- vs ARv567es+ (92% vs 57%; p=0.04) patients. When AR-V mRNA status was
      correlated with change in nuclear AR from Cycle 1 Day 1 to 8 (n=24), AR-V7+
      patients (n=16) had a 0.4% decrease vs a 12.9% and 26.7% decrease in AR-V7
      /ARv567es- (n=3) and AR-V7-/ ARv567es+ (n=5) patients, respectively, suggesting a
      dominant role for AR-V7 over ARv567es.Median PFS was 12.02 vs 8.48 months for AR
      V7- vs AR-V7+ (HR=0.38; p=0.01), and 12.71 vs 7.29 months for ARv567es- vs
      ARv567es+ (HR=0.37; p=0.02). For AR-V7+, AR-V7-/ARv567es+, and AR-V7-/ ARv567es-
      patients, median PFS was 8.48, 11.17 and 16.62 months, respectively (trend:
      p=0.0013). CONCLUSIONS: Detection of CTC-specific AR-V7 and ARv567es by ddPCR
      influenced taxane outcomes; AR-V7 primarily mediated the prognostic impact.
      Absence of both variants was associated with best response and PFS with taxanes.

PMID- 30301830
TI  - Congolese gynaecologist shares Nobel peace prize for work with war rape victims.

PMID- 30301831
TI  - Director of troubled Karolinska hospital resigns.

PMID- 30301832
TI  - scaRNAs and snoRNAs: Are they limited to specific classes of substrate RNAs?
AB  - Posttranscriptional modifications of rRNA occur in the nucleolus where rRNA
      modification guide RNAs, or snoRNAs, concentrate. On the other hand, scaRNAs, the
      modification guide RNAs for spliceosomal snRNAs, concentrate in the Cajal body
      (CB). It is generally assumed, therefore, that snRNAs must accumulate in CBs to
      be modified by scaRNAs. Here we demonstrate that the evidence for the latter
      postulate is not consistent. In the nucleus, scaRNA localization is not limited
      to CBs. Furthermore, canonical scaRNAs can modify rRNAs. We suggest that the
      conventional view that scaRNAs function only in the CB needs revision.

PMID- 30301833
TI  - Unilateral rhinorrhoea associated with cerebrospinal fluid leak.

PMID- 30301834
TI  - Red cell distribution width in coronary heart disease: prediction of restenosis
      and its relationship with inflammatory markers and lipids.
AB  - BACKGROUND: Red cell distribution width (RDW) is associated with a poor prognosis
      and adverse events in cardiovascular diseases. The aims of this study were to
      investigate the relationship between serum RDW levels and outcomes after
      percutaneous coronary intervention and to identify potential novel laboratory
      markers for evaluating the risk of in-stent restenosis (ISR) with stable angina
      pectoris. METHODS: A total of 261 patients with coronary heart disease from
      Dongfeng General Hospital implanted with a coronary drug-eluting stent (DES) were
      enrolled in the study. We retrospectively analysed the role and prognosis values
      of serum parameters that were measured before angiography at the first admission.
      According to the results of the second angiogram, the patients were divided into
      two groups as follows: the non-ISR group (n=143) and the ISR group (n=118). The
      clinical characteristics and all laboratory data were considered for univariate
      and multivariate logistic regression analyses. RESULTS: The white cell count,
      RDW, neutrophil count, C-reactive protein (CRP), total cholesterol, low-density
      lipoprotein cholesterol (LDL-C), blood urea nitrogen and uric acid levels were
      higher in the ISR group than in the non-ISR group. There were no differences in
      the rates of hypertension, fasting plasma glucose, red cell count, neutrophil to
      lymphocyte ratio, platelet count, triglyceride, high-density lipoprotein
      cholesterol and creatinine levels. In the univariate regression analysis, age,
      diabetes, white cell count, neutrophil count, RDW, CRP, total cholesterol, LDL-C,
      blood urea nitrogen, Gensini score and number of stents were predictors of ISR.
      According to the multiple logistic regression analysis, age, RDW and number of
      stents were independent predictors of ISR. CONCLUSIONS: Preprocedural blood
      parameters can independently predict ISR. Our study results demonstrated that a
      high preprocedural RDW is an independent predictor of DES restenosis.

PMID- 30301835
TI  - A long wait: barriers to discharge for long length of stay patients.
AB  - INTRODUCTION: Reducing long length of stay (LLOS, or inpatient stays lasting over
      30 days) is an important way for hospitals to improve cost efficiency, bed
      availability and health outcomes. Discharge delays can cost hundreds to thousands
      of dollars per patient, and LLOS represents a burden on bed availability for
      other potential patients. However, most research studies investigating discharge
      barriers are not LLOS-specific. Of those that do, nearly all are limited by
      further patient subpopulation focus or small sample size. To our knowledge, our
      study is the first to describe LLOS discharge barriers in an entire Department of
      Medicine. METHODS: We conducted a chart review of 172 LLOS patients in the
      Department of Medicine at an academic tertiary care hospital and quantified the
      most frequent causes of delay as well as factors causing the greatest amount of
      delay time. We also interviewed healthcare staff for their perceptions on
      barriers to discharge. RESULTS: Discharge site coordination was the most frequent
      cause of delay, affecting 56% of patients and accounting for 80% of total non
      medical postponement days. Goals of care issues and establishment of follow-up
      care were the next most frequent contributors to delay. CONCLUSION: Together with
      perspectives from interviewed staff, these results highlight multiple different
      areas of opportunity for reducing LLOS and maximising the care capacity of
      inpatient hospitals.

PMID- 30301836
TI  - How to pass the Part 1 FRCOphth in foundation training.

PMID- 30301837
TI  - The Role of WNT Signaling in Mature T Cells: T Cell Factor Is Coming Home.
AB  - T cell factor, the effector transcription factor of the WNT signaling pathway,
      was so named because of the primary observation that it is indispensable for T
      cell development in the thymus. Since this discovery, the role of this signaling
      pathway has been extensively studied in T cell development, hematopoiesis, and
      stem cells; however, its functional role in mature T cells has remained
      relatively underinvestigated. Over the last few years, various studies have
      demonstrated that T cell factor can directly influence T cell function and the
      differentiation of Th1, Th2, Th17, regulatory T cell, follicular helper CD4+ T
      cell subsets, and CD8+ memory T cells. In this paper, we discuss the molecular
      mechanisms underlying these observations and place them in the general context of
      immune responses. Furthermore, we explore the implications and limitations of
      these findings for WNT manipulation as a therapeutic approach for treating immune
      related diseases.

PMID- 30301838
TI  - A multimodal molecular imaging study evaluates pharmacological alteration of the
      tumor microenvironment to improve radiation response.
AB  - Hypoxic zones in solid tumors contribute to radioresistance, and pharmacological
      agents that increase tumor oxygenation prior to radiation, including anti
      angiogenic drugs, can enhance treatment response to radiotherapy. Although such
      strategies have been applied, imaging assessments of tumor oxygenation to
      identify an optimum time window for radiotherapy have not been fully explored. In
      this study, we investigated the effects of alpha-sulfoquinovosylacyl-1,3
      propanediol (SQAP; a synthetic derivative of an anti-angiogenic agent) on the
      tumor microenvironment in terms of oxygen partial pressure (pO2), oxyhemoglobin
      saturation (sO2), blood perfusion, and microvessel density using electron
      paramagnetic resonance imaging, photoacoustic imaging, dynamic contrast-enhanced
      MRI with Gd-DTPA injection, and T2*-weighted imaging with ultrasmall
      superparamagnetic iron oxide (USPIO) contrast. SCCVII and A549 tumors were grown
      by injecting tumor cells into the hind legs of mice. Five days of daily radiation
      (2 Gy) combined with intravenous injection of SQAP (2 mg/kg) 30 min prior to
      irradiation significantly delayed growth of tumor xenografts. Three days of daily
      treatment improved tumor oxygenation and decreased tumor microvascular density on
      T2*-weighted images with USPIO, suggesting vascular normalization. Acute effects
      of SQAP on tumor oxygenation were examined by pO2, sO2, and Gd-DTPA contrast
      enhanced imaging. SQAP treatment improved perfusion and tumor pO2 (DeltapO2:
      3.1+/-1.0 mmHg) and was accompanied by decreased sO2 (20-30% decrease) in SCCVII
      implants 20-30 min after SQAP administration. These results provide evidence that
      SQAP transiently enhances tumor oxygenation by facilitating oxygen dissociation
      from oxyhemoglobin and improving tumor perfusion. Therefore, SQAP-mediated
      sensitization to radiation in vivo can be attributed to increased tumor
      oxygenation.

PMID- 30301839
TI  - LPA4-Mediated Vascular Network Formation Increases the Efficacy of Anti-PD-1
      Therapy against Brain Tumors.
AB  - : The structure and function of tumor blood vessels profoundly affects the tumor
      microenvironment. Signals mediated through the lysophosphatidic acid receptor 4
      (LPA4) promote vascular network formation to restore normal vascular barrier
      function in subcutaneous tumors and thus improve drug delivery. However, the
      characteristics of the vasculature vary by organ and tumor types, and how drug
      delivery and leukocyte trafficking are affected by modification of vascular
      function by LPA in different cancers is unclear. Here, we show that LPA4
      activation promotes the formation of fine vascular structures in brain tumors.
      RhoA/ROCK signaling contributed to LPA-induced endothelial cell-cell adhesion,
      and RhoA/ROCK activity following LPA4 stimulation regulated expression of VCAM-1.
      This resulted in increased lymphocyte infiltration into the tumor. LPA improved
      delivery of exogenous IgG into brain tumors and enhanced the anticancer effect of
      anti-programmed cell death-1 antibody therapy. These results indicate the effects
      of LPA on vascular structure and function apply not only to chemotherapy but also
      to immunotherapy. SIGNIFICANCE: These findings demonstrate that lysophosphatidic
      acid, a lipid mediator, promotes development of a fine capillary network in brain
      tumors by inducing tightening of endothelial cell-to-cell adhesion, facilitating
      improved drug delivery, and lymphocyte penetration.

PMID- 30301840
TI  - A p53-Responsive miRNA Network Promotes Cancer Cell Quiescence.
AB  - : Cancer cells in quiescence (G0 phase) are resistant to death, and re-entry of
      quiescent cancer cells into the cell-cycle plays an important role in cancer
      recurrence. Here we show that two p53-responsive miRNAs utilize distinct but
      complementary mechanisms to promote cancer cell quiescence by facilitating
      stabilization of p27. Purified quiescent B16 mouse melanoma cells expressed
      higher levels of miRNA-27b-3p and miRNA-455-3p relative to their proliferating
      counterparts. Induction of quiescence resulted in increased levels of these
      miRNAs in diverse types of human cancer cell lines. Inhibition of miRNA-27b-3p or
      miRNA-455-3p reduced, whereas its overexpression increased, the proportion of
      quiescent cells in the population, indicating that these miRNAs promote cancer
      cell quiescence. Accordingly, cancer xenografts bearing miRNA-27b-3p or miRNA-455
      3p mimics were retarded in growth. miRNA-27b-3p targeted cyclin-dependent kinase
      regulatory subunit 1 (CKS1B), leading to reduction in p27 polyubiquitination
      mediated by S-phase kinase-associated protein 2 (Skp2). miRNA-455-3p targeted
      CDK2-associated cullin domain 1 (CAC1), which enhanced CDK2-mediated
      phosphorylation of p27 necessary for its polyubiquitination. Of note, the gene
      encoding miRNA-27b-3p was embedded in the intron of the chromosome 9 open reading
      frame 3 gene that was transcriptionally activated by p53. Similarly, the host
      gene of miRNA-455-3p, collagen alpha-1 (XXVII) chain, was also a p53
      transcriptional target. Collectively, our results identify miRNA-27b-3p and miRNA
      455-3p as important regulators of cancer cell quiescence in response to p53 and
      suggest that manipulating miRNA-27b-3p and miRNA-455-3p may constitute novel
      therapeutic avenues for improving outcomes of cancer treatment. SIGNIFICANCE: Two
      novel p53-responsive microRNAs whose distinct mechanisms of action both stabilize
      p27 to promote cell quiescence and may serve as therapeutic avenues for improving
      outcomes of cancer treatment.

PMID- 30301841
TI  - Probing the mechanisms of extracellular vesicle biogenesis and function in
      cancer.
AB  - Tumor cells interact with each other, and their surroundings, using a variety of
      mechanisms to promote virtually all aspects of cancer progression. One such form
      of intercellular communication that has been attracting considerable attention
      from the cancer community and the pharmaceutical industry in recent years
      involves the ability of cancer cells to generate multiple distinct types of non
      classical secretory vesicles, generally referred to as extracellular vesicles
      (EVs). Microvesicles (MVs) represent one of the major classes of EVs and are
      formed as a result of the outward budding and fission of the plasma membrane. The
      other main class of EVs is exosomes, which are generated when multivesicular
      bodies fuse with the cell surface and release their contents into the
      extracellular space. Both MVs and exosomes have been shown to contain bioactive
      cargo, including proteins, metabolites, RNA transcripts, microRNAs, and DNA that
      can be transferred to other cancer cells and stimulate their growth, survival,
      and migration. However, cancer cell-derived EVs also play important roles in
      helping re-shape the tumor microenvironment to support tumor expansion and
      invasive activity, dampen immune responses, as well as enter the circulation to
      help promote metastatic spread. Here, we provide an overview of what is currently
      known regarding how the different classes of EVs are generated and contribute to
      various cancer cell phenotypes. Moreover, we highlight how some of the unique
      properties of EVs are being used for the development of novel diagnostic and
      clinical applications.

PMID- 30301843
TI  - Mimicry and functions of photosynthetic reaction centers.
AB  - The structure and function of photosynthetic reaction centers (PRCs) have been
      modeled by designing and synthesizing electron donor-acceptor ensembles including
      electron mediators, which can mimic multi-step photoinduced charge separation
      occurring in PRCs to obtain long-lived charge-separated states. PRCs in
      photosystem I (PSI) or/and photosystem II (PSII) have been utilized as components
      of solar cells to convert solar energy to electric energy. Biohybrid
      photoelectrochemical cells composed of PSII have also been developed for solar
      driven water splitting into H2 and O2 Such a strategy to bridge natural
      photosynthesis with artificial photosynthesis is discussed in this minireview.

PMID- 30301844
TI  - New perspectives on IL-33 and IL-1 family cytokines as innate environmental
      sensors.
AB  - Interleukin (IL)-1 family cytokines are important initiators of innate immunity
      and host defence; however, their uncontrolled activities can cause tissue
      damaging inflammation. Consequently, IL-1 family cytokines have sophisticated
      regulatory mechanisms to control their activities including proteolytic
      processing for their activation and the deployment of soluble receptors and
      receptor antagonists to limit their activities. IL-33 is a promoter of type 2
      immunity and allergic inflammation through its alarmin activity that can rapidly
      initiate local immune responses by stimulating innate immune cells following
      exposure to environmental insults, pathogens, or sterile injury. Recent
      publications have provided new insights into how the range and duration of IL-33
      activity is regulated by direct sensing of host-derived and exogenous proteolytic
      activities as well as oxidative changes during tissue damage. Here, we discuss
      how this impacts our understanding of the roles of IL-33 in initiating immune
      responses and the evidence that these sensing mechanisms might regulate the
      activities of other IL-1 family cytokines and their biological functions.
      Finally, we discuss translational challenges these discoveries pose for the
      accurate detection of different forms of these cytokines.

PMID- 30301845
TI  - Allostery and dynamics in small G proteins.
AB  - The Ras family of small guanine nucleotide-binding proteins behave as molecular
      switches: they are switched off and inactive when bound to GDP but can be
      activated by GTP binding in response to signal transduction pathways. Early
      structural analysis showed that two regions of the protein, which change
      conformation depending on the nucleotide present, mediate this switch. A large
      number of X-ray, NMR and simulation studies have shown that this is an over
      simplification. The switch regions themselves are highly dynamic and can exist in
      distinct sub-states in the GTP-bound form that have different affinities for
      other proteins. Furthermore, regions outside the switches have been found to be
      sensitive to the nucleotide state of the protein, indicating that allosteric
      change is more widespread than previously thought. Taken together, the accrued
      knowledge about small G protein structures, allostery and dynamics will be
      essential for the design and testing of the next generation of inhibitors, both
      orthosteric and allosteric, as well as for understanding their mode of action.

PMID- 30301842
TI  - Vitamin C and immune cell function in inflammation and cancer.
AB  - Vitamin C (ascorbate) is maintained at high levels in most immune cells and can
      affect many aspects of the immune response. Intracellular levels generally
      respond to variations in plasma ascorbate availability, and a combination of
      inadequate intake and increased turnover during severe stress can result in low
      plasma ascorbate status. Intracellular ascorbate supports essential functions
      and, in particular, acts as an enzyme cofactor for Fe- or Cu-containing
      oxygenases. Newly discovered enzymes in this family regulate cell metabolism and
      epigenetics, and dysregulation of their activity can affect cell phenotype,
      growth and survival pathways, and stem cell phenotype. This brief overview
      details some of the recent advances in our understanding of how ascorbate
      availability can affect the hydroxylases controlling the hypoxic response and the
      DNA and histone demethylases. These processes play important roles in the
      regulation of the immune system, altering cell survival pathways, metabolism and
      functions.

PMID- 30301847
TI  - Is mitochondrial gene expression coordinated or stochastic?
AB  - Mitochondrial biogenesis is intimately dependent on the coordinated expression of
      the nuclear and mitochondrial genomes that is necessary for the assembly and
      function of the respiratory complexes to produce most of the energy required by
      cells. Although highly compacted in animals, the mitochondrial genome and its
      expression are essential for survival, development, and optimal energy
      production. The machinery that regulates gene expression within mitochondria is
      localised within the same compartment and, like in their ancestors, the bacteria,
      this machinery does not use membrane-based compartmentalisation to order the gene
      expression pathway. Therefore, the lifecycle of mitochondrial RNAs from
      transcription through processing, maturation, translation to turnover is mediated
      by a gamut of RNA-binding proteins (RBPs), all contained within the mitochondrial
      matrix milieu. Recent discoveries indicate that multiple processes regulating RNA
      metabolism occur at once but since mitochondria have a new complement of RBPs,
      many evolved de novo from nuclear genes, we are left wondering how co-ordinated
      are these processes? Here, we review recently identified examples of the co
      ordinated and stochastic processes that govern the mitochondrial transcriptome.
      These new discoveries reveal the complexity of mitochondrial gene expression and
      the need for its in-depth exploration to understand how these organelles can
      respond to the energy demands of the cell.

PMID- 30301846
TI  - Towards a therapy for mitochondrial disease: an update.
AB  - Preclinical work aimed at developing new therapies for mitochondrial diseases has
      recently given new hopes and opened unexpected perspectives for the patients
      affected by these pathologies. In contrast, only minor progresses have been
      achieved so far in the translation into the clinics. Many challenges are still
      ahead, including the need for a better characterization of the pharmacological
      effects of the different approaches and the design of appropriate clinical trials
      with robust outcome measures for this extremely heterogeneous, rare, and complex
      group of disorders. In this review, we will discuss the most important
      achievements and the major challenges in this very dynamic research field.

PMID- 30301848
TI  - The Multifaceted Antibacterial Mechanisms of the Pioneering Peptide Antibiotics
      Tyrocidine and Gramicidin S.
AB  - Cyclic beta-sheet decapeptides from the tyrocidine group and the homologous
      gramicidin S were the first commercially used antibiotics, yet it remains unclear
      exactly how they kill bacteria. We investigated their mode of action using a
      bacterial cytological profiling approach. Tyrocidines form defined ion-conducting
      pores, induce lipid phase separation, and strongly reduce membrane fluidity,
      resulting in delocalization of a broad range of peripheral and integral membrane
      proteins. Interestingly, they also cause DNA damage and interfere with DNA
      binding proteins. Despite sharing 50% sequence identity with tyrocidines,
      gramicidin S causes only mild lipid demixing with minor effects on membrane
      fluidity and permeability. Gramicidin S delocalizes peripheral membrane proteins
      involved in cell division and cell envelope synthesis but does not affect
      integral membrane proteins or DNA. Our results shed a new light on the
      multifaceted antibacterial mechanisms of these antibiotics and explain why
      resistance to them is virtually nonexistent.IMPORTANCE Cyclic beta-sheet
      decapeptides, such as tyrocidines and gramicidin S, were among the first
      antibiotics in clinical application. Although they have been used for such a long
      time, there is virtually no resistance to them, which has led to a renewed
      interest in this peptide class. Both tyrocidines and gramicidin S are thought to
      disrupt the bacterial membrane. However, this knowledge is mainly derived from in
      vitro studies, and there is surprisingly little knowledge about how these long
      established antibiotics kill bacteria. Our results shed new light on the
      antibacterial mechanism of beta-sheet peptide antibiotics and explain why they
      are still so effective and why there is so little resistance to them.

PMID- 30301849
TI  - Rethinking the Coral Microbiome: Simplicity Exists within a Diverse Microbial
      Biosphere.
AB  - Studies of the coral microbiome predominantly characterize the microbial
      community of the host species as a collective, rather than that of the
      individual. This ecological perspective on the coral microbiome has led to the
      conclusion that the coral holobiont is the most diverse microbial biosphere
      studied thus far. However, investigating the microbiome of the individual, rather
      than that of the species, highlights common and conserved community attributes
      which can provide insights into the significance of microbial associations to the
      host. Here, we show there are consistent characteristics between individuals in
      the proposed three components of the coral microbiome (i.e., "environmentally
      responsive community," "resident or individual microbiome," and "core
      microbiome"). We found that the resident microbiome of a photoendosymbiotic coral
      harbored <3% (~605 phylotypes) of the 16S rRNA phylotypes associated with all
      investigated individuals of that species ("species-specific microbiome") (~21,654
      phylotypes; individuals from Pachyseris speciosa [n = 123], Mycedium elephantotus
      [n = 95], and Acropora aculeus [n = 91] from 10 reef locations). The remaining
      bacterial phylotypes (>96%) (environmentally responsive community) of the species
      specific microbiome were in fact not found in association with the majority of
      individuals of the species. Only 0.1% (~21 phylotypes) of the species-specific
      microbiome of each species was shared among all individuals of the species (core
      microbiome), equating to ~3.4% of the resident microbiome. We found taxonomic
      redundancy and consistent patterns of composition, structure, and taxonomic
      breadth across individual microbiomes from the three coral species. Our results
      demonstrate that the coral microbiome is structured at the individual
      level.IMPORTANCE We propose that the coral holobiont should be conceptualized as
      a diverse transient microbial community that is responsive to the surrounding
      environment and encompasses a simple, redundant, resident microbiome and a small
      conserved core microbiome. Most importantly, we show that the coral microbiome is
      comparable to the microbiomes of other organisms studied thus far. Accurately
      characterizing the coral-microbe interactions provides an important baseline from
      which the functional roles and the functional niches within which microbes reside
      can be deciphered.

PMID- 30301850
TI  - Arylvinylpiperazine Amides, a New Class of Potent Inhibitors Targeting QcrB of
      Mycobacterium tuberculosis.
AB  - New drugs are needed to control the current tuberculosis (TB) pandemic caused by
      infection with Mycobacterium tuberculosis We report here on our work with AX-35,
      an arylvinylpiperazine amide, and four related analogs, which are potent
      antitubercular agents in vitro All five compounds showed good activity against M.
      tuberculosis in vitro and in infected THP-1 macrophages, while displaying only
      mild cytotoxicity. Isolation and characterization of M. tuberculosis-resistant
      mutants to the arylvinylpiperazine amide derivative AX-35 revealed mutations in
      the qcrB gene encoding a subunit of cytochrome bc 1 oxidase, one of two terminal
      oxidases of the electron transport chain. Cross-resistance studies, allelic
      exchange, transcriptomic analyses, and bioenergetic flux assays provided
      conclusive evidence that the cytochrome bc 1 -aa 3 is the target of AX-35,
      although the compound appears to interact differently with the quinol binding
      pocket compared to previous QcrB inhibitors. The transcriptomic and bioenergetic
      profiles of M. tuberculosis treated with AX-35 were similar to those generated by
      other cytochrome bc 1 oxidase inhibitors, including the compensatory role of the
      alternate terminal oxidase cytochrome bd in respiratory adaptation. In the
      absence of cytochrome bd oxidase, AX-35 was bactericidal against M. tuberculosis
      Finally, AX-35 and its analogs were active in an acute mouse model of TB
      infection, with two analogs displaying improved activity over the parent
      compound. Our findings will guide future lead optimization to produce a drug
      candidate for the treatment of TB and other mycobacterial diseases, including
      Buruli ulcer and leprosy.IMPORTANCE New drugs against Mycobacterium tuberculosis
      are urgently needed to deal with the current global TB pandemic. We report here
      on the discovery of a series of arylvinylpiperazine amides (AX-35 to AX-39) that
      represent a promising new family of compounds with potent in vitro and in vivo
      activities against M. tuberculosis AX compounds target the QcrB subunit of the
      cytochrome bc 1 terminal oxidase with a different mode of interaction compared to
      those of known QcrB inhibitors. This study provides the first multifaceted
      validation of QcrB inhibition by recombineering-mediated allelic exchange, gene
      expression profiling, and bioenergetic flux studies. It also provides further
      evidence for the compensatory role of cytochrome bd oxidase upon QcrB inhibition.
      In the absence of cytochrome bd oxidase, AX compounds are bactericidal, an
      encouraging property for future antimycobacterial drug development.

PMID- 30301852
TI  - A Natural History of Actinic Keratosis and Cutaneous Squamous Cell Carcinoma
      Microbiomes.
AB  - Cutaneous squamous cell carcinoma (SCC) is the second-most-common cancer in
      Australia. The majority of SCCs progress from premalignant actinic keratosis (AK)
      lesions that form on chronically sun-exposed skin. The role of skin microbiota in
      this progression is not well understood; therefore, we performed a longitudinal
      microbiome analysis of AKs and SCCs using a cohort of 13 SCC-prone
      immunocompetent men. The majority of variability in microbial profiles was
      attributable to subject, followed by time and lesion type. Propionibacterium and
      Malassezia organisms were relatively more abundant in nonlesional photodamaged
      skin than in AKs and SCCs. Staphylococcus was most commonly associated with
      lesional skin, in particular, sequences most closely related to Staphylococcus
      aureus Of 11 S. aureus-like operational taxonomic units (OTUs), six were
      significantly associated with SCC lesions across seven subjects, suggesting their
      specific involvement with AK-to-SCC progression. If a causative link exists
      between certain S. aureus-like OTUs and SCC etiology, therapeutic approaches
      specifically targeting these bacteria could be used to reduce SCC.IMPORTANCE
      Actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) are two of the
      most common dermatologic conditions in Western countries and cause substantial
      morbidity worldwide. The role of human papillomaviruses under these conditions
      has been well studied yet remains inconclusive. One PCR-based study has
      investigated bacteria in the etiology of these conditions; however, no study has
      investigated the microbiomes of AK and SCC more broadly. We longitudinally
      profiled the microbiomes of 112 AK lesions, profiled cross sections of 32
      spontaneously arising SCC lesions, and compared these to matching nonlesional
      photodamaged control skin sites. We identified commonly occurring strains of
      Propionibacterium and Malassezia at higher relative abundances on nonlesional
      skin than in AK and SCC lesions, and strains of Staphylococcus aureus were
      relatively more abundant in lesional than nonlesional skin. These findings may
      aid in the prevention of SCC.

PMID- 30301851
TI  - Evolution of the Arsenal of Legionella pneumophila Effectors To Modulate Protist
      Hosts.
AB  - Within the human host, Legionella pneumophila replicates within alveolar
      macrophages, leading to pneumonia. However, L. pneumophila is an aquatic
      generalist pathogen that replicates within a wide variety of protist hosts,
      including amoebozoa, percolozoa, and ciliophora. The intracellular lifestyles of
      L. pneumophila within the two evolutionarily distant hosts macrophages and
      protists are remarkably similar. Coevolution with numerous protist hosts has
      shaped plasticity of the genome of L. pneumophila, which harbors numerous
      proteins encoded by genes acquired from primitive eukaryotic hosts through
      interkingdom horizontal gene transfer. The Dot/Icm type IVb translocation system
      translocates ~6,000 effectors among Legionella species and >320 effector proteins
      in L. pneumophila into host cells to modulate a plethora of cellular processes to
      create proliferative niches. Since many of the effectors have likely evolved to
      modulate cellular processes of primitive eukaryotic hosts, it is not surprising
      that most of the effectors do not contribute to intracellular growth within human
      macrophages. Some of the effectors may modulate highly conserved eukaryotic
      processes, while others may target protist-specific processes that are absent in
      mammals. The lack of studies to determine the role of the effectors in adaptation
      of L. pneumophila to various protists has hampered the progress to determine the
      function of most of these effectors, which are routinely studied in mouse or
      human macrophages. Since many protists restrict L. pneumophila, utilization of
      such hosts can also be instrumental in deciphering the mechanisms of failure of
      L. pneumophila to overcome restriction of certain protist hosts. Here, we review
      the interaction of L. pneumophila with its permissive and restrictive protist
      environmental hosts and outline the accomplishments as well as gaps in our
      knowledge of L. pneumophila-protist host interaction and L. pneumophila's
      evolution to become a human pathogen.

PMID- 30301854
TI  - Pathogenicity of Serratia marcescens Strains in Honey Bees.
AB  - Although few honey bee diseases are known to be caused by bacteria, pathogens of
      adult worker bees may be underrecognized due to social immunity mechanisms.
      Specifically, infected adult bees typically abandon the hive or are removed by
      guards. Serratia marcescens, an opportunistic pathogen of many plants and
      animals, is often present at low abundance in the guts of honey bee workers and
      has recently been isolated from Varroa mites and from the hemolymph of dead and
      dying honey bees. However, the severity and prevalence of S. marcescens
      pathogenicity in honey bees have not been fully investigated. Here we
      characterized three S. marcescens strains isolated from the guts of honey bees
      and one previously isolated from hemolymph. In vivo tests confirmed that S.
      marcescens is pathogenic in workers. All strains caused mortality when a few
      cells were injected into the hemocoel, and the gut-isolated strains caused
      mortality when administered orally. In vitro assays and comparative genomics
      identified possible mechanisms of virulence of gut-associated strains. Expression
      of antimicrobial peptide and phenoloxidase genes was not elevated following
      infection, suggesting that these S. marcescens strains derived from honey bees
      can evade the immune response in their hosts. Finally, surveys from four
      locations in the United States indicated the presence of S. marcescens in the
      guts of over 60% of the worker bees evaluated. Taken together, these results
      suggest that S. marcescens is a widespread opportunistic pathogen of adult honey
      bees and that it may be highly virulent under some conditions such as
      perturbation of the normal gut microbiota or the presence of Varroa mites that
      puncture the integument, thereby enabling entry of bacterial cells.IMPORTANCE
      Recently, it has become apparent that multiple factors are responsible for honey
      bee decline, including climate change, pests and pathogens, pesticides, and loss
      of foraging habitat. Of the large number of pathogens known to infect honey bees,
      very few are bacteria. Because adult workers abandon hives when diseased, many of
      their pathogens may go unnoticed. Here we characterized the virulence of Serratia
      marcescens strains isolated from honey bee guts and hemolymph. Our results
      indicate that S. marcescens, an opportunistic pathogen of many plants and
      animals, including humans, is a virulent opportunistic pathogen of honey bees,
      which could contribute to bee decline. Aside from the implications for honey bee
      health, the discovery of pathogenic S. marcescens strains in honey bees presents
      an opportunity to better understand how opportunistic pathogens infect and invade
      hosts.

PMID- 30301853
TI  - Octopaminergic Signaling Mediates Neural Regulation of Innate Immunity in
      Caenorhabditis elegans.
AB  - Upon pathogen infection, the nervous system regulates innate immunity to confer
      coordinated protection to the host. However, the precise mechanisms of such
      regulation remain unclear. Previous studies have demonstrated that OCTR-1, a
      putative G protein-coupled receptor for catecholamine, functions in the sensory
      neurons designated "ASH" to suppress innate immune responses in Caenorhabditis
      elegans It is unknown what molecules act as OCTR-1 ligands in the neural immune
      regulatory circuit. Here we identify neurotransmitter octopamine (OA) as an
      endogenous ligand for OCTR-1 in immune regulation and show that the OA-producing
      RIC neurons function in the OCTR-1 neural circuit to suppress innate immunity.
      RIC neurons are deactivated in the presence of pathogens but transiently
      activated by nonpathogenic bacteria. Our data support a model whereby an
      octopaminergic immunoinhibitory pathway is tonically active under normal
      conditions to maintain immunological homeostasis or suppress unwanted innate
      immune responses but downregulated upon pathogen infection to allow enhanced
      innate immunity. As excessive innate immune responses have been linked to a
      myriad of human health concerns, our study could potentially benefit the
      development of more-effective treatments for innate immune disorders.IMPORTANCE
      Insufficient or excessive immune responses to pathogen infection are major causes
      of disease. Increasing evidence indicates that the nervous system regulates the
      immune system to help maintain immunological homeostasis. However, the precise
      mechanisms of this regulation are largely unknown. Here we show the existence of
      an octopaminergic immunoinhibitory pathway in Caenorhabditis elegans Our study
      results indicate that this pathway is tonically active under normal conditions to
      maintain immunological homeostasis or suppress unwanted innate immune responses
      but downregulated upon pathogen infection to allow enhanced innate immunity. As
      excessive innate immune responses have been linked to human health conditions
      such as Crohn's disease, rheumatoid arthritis, atherosclerosis, diabetes, and
      Alzheimer's disease, elucidating octopaminergic neural regulation of innate
      immunity could be helpful in the development of new treatments for innate immune
      diseases.

PMID- 30301855
TI  - Inducible Nitric Oxide Synthase Is a Key Host Factor for Toxoplasma GRA15
      Dependent Disruption of the Gamma Interferon-Induced Antiparasitic Human
      Response.
AB  - Although Toxoplasma virulence mechanisms targeting gamma interferon (IFN-gamma)
      induced cell-autonomous antiparasitic immunity have been extensively
      characterized in mice, the virulence mechanisms in humans remain uncertain,
      partly because cell-autonomous immune responses against Toxoplasma differ
      markedly between mice and humans. Despite the identification of inducible nitric
      oxide synthase (iNOS) as an anti-Toxoplasma host factor in mice, here we show
      that iNOS in humans is a pro-Toxoplasma host factor that promotes the growth of
      the parasite. The GRA15 Toxoplasma effector-dependent disarmament of IFN-gamma
      induced parasite growth inhibition was evident when parasite-infected monocytes
      were cocultured with hepatocytes. Interleukin-1beta (IL-1beta), produced from
      monocytes in a manner dependent on GRA15 and the host's NLRP3 inflammasome,
      combined with IFN-gamma to strongly stimulate iNOS expression in hepatocytes;
      this dramatically reduced the levels of indole 2,3-dioxygenase 1 (IDO1), a
      critically important IFN-gamma-inducible anti-Toxoplasma protein in humans, thus
      allowing parasite growth. Taking the data together, Toxoplasma utilizes human
      iNOS to antagonize IFN-gamma-induced IDO1-mediated cell-autonomous immunity via
      its GRA15 virulence factor.IMPORTANCE Toxoplasma, an important intracellular
      parasite of humans and animals, causes life-threatening toxoplasmosis in
      immunocompromised individuals. Gamma interferon (IFN-gamma) is produced in the
      host to inhibit the proliferation of this parasite and eventually cause its
      death. Unlike mouse disease models, which involve well-characterized virulence
      strategies that are used by Toxoplasma to suppress IFN-gamma-dependent immunity,
      the strategies used by Toxoplasma in humans remain unclear. Here, we show that
      GRA15, a Toxoplasma effector protein, suppresses the IFN-gamma-induced indole-2,3
      dioxygenase 1-dependent antiparasite immune response in human cells. Because
      NLRP3-dependent production of IL-1beta and nitric oxide (NO) in Toxoplasma
      infected human cells is involved in the GRA15-dependent virulence mechanism,
      blocking NO or IL-1beta production in the host could represent a novel
      therapeutic approach for treating human toxoplasmosis.

PMID- 30301856
TI  - Complement Activation Contributes to Severe Acute Respiratory Syndrome
      Coronavirus Pathogenesis.
AB  - Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are
      observed in severe cases of severe acute respiratory syndrome coronavirus (SARS
      CoV) infection. SARS-CoV emerged in 2002 to 2003 and led to a global outbreak of
      SARS. As with the outcome of human infection, intranasal infection of C57BL/6J
      mice with mouse-adapted SARS-CoV results in high-titer virus replication within
      the lung, induction of inflammatory cytokines and chemokines, and immune cell
      infiltration within the lung. Using this model, we investigated the role of the
      complement system during SARS-CoV infection. We observed activation of the
      complement cascade in the lung as early as day 1 following SARS-CoV infection. To
      test whether this activation contributed to protective or pathologic outcomes, we
      utilized mice deficient in C3 (C3-/-), the central component of the complement
      system. Relative to C57BL/6J control mice, SARS-CoV-infected C3 -/- mice
      exhibited significantly less weight loss and less respiratory dysfunction despite
      equivalent viral loads in the lung. Significantly fewer neutrophils and
      inflammatory monocytes were present in the lungs of C3 -/- mice than in C56BL/6J
      controls, and subsequent studies revealed reduced lung pathology and lower
      cytokine and chemokine levels in both the lungs and the sera of C3 -/- mice than
      in controls. These studies identify the complement system as an important host
      mediator of SARS-CoV-induced disease and suggest that complement activation
      regulates a systemic proinflammatory response to SARS-CoV infection. Furthermore,
      these data suggest that SARS-CoV-mediated disease is largely immune driven and
      that inhibiting complement signaling after SARS-CoV infection might function as
      an effective immune therapeutic.IMPORTANCE The complement system is a critical
      part of host defense to many bacterial, viral, and fungal infections. It works
      alongside pattern recognition receptors to stimulate host defense systems in
      advance of activation of the adaptive immune response. In this study, we directly
      test the role of complement in SARS-CoV pathogenesis using a mouse model and show
      that respiratory disease is significantly reduced in the absence of complement
      even though viral load is unchanged. Complement-deficient mice have reduced
      neutrophilia in their lungs and reduced systemic inflammation, consistent with
      the observation that SARS-CoV pathogenesis is an immune-driven disease. These
      data suggest that inhibition of complement signaling might be an effective
      treatment option following coronavirus infection.

PMID- 30301858
TI  - Host-Pathogen Interactions: What the EHEC Are We Learning from Host Genome-Wide
      Screens?
AB  - Several genome-wide screens have been conducted to identify host cell factors
      involved in the pathogenesis of bacterial pathogens whose virulence is dependent
      on type III secretion systems (T3SSs), nanomachines responsible for the
      translocation of proteins into host cells. In the most recent of these, Pacheco
      et al. (mBio 9:e01003-18, 2018, http://mbio.asm.org/content/9/3/e01003-18.full)
      screened a genome-wide CRISPR/Cas9 (clustered regularly interspaced short
      palindromic repeats with Cas9) knockout library for host proteins involved in the
      pathogenesis of enterohemorrhagic Escherichia coli (EHEC). Their study revealed
      an unrecognized link between EHEC's two major virulence determinants (its T3SS
      and Shiga toxins). We discuss these findings in light of data from three other
      genome-wide screens. Each of these studies uncovered multiple host cell
      determinants, which curiously share little to no overlap but primarily are
      involved in mediating early interactions between T3SSs and host cells. We
      therefore consider how each screen was performed, the advantages and
      disadvantages of each, and how follow-up studies might be designed to address
      these issues.

PMID- 30301857
TI  - Staufen1 Interacts with Multiple Components of the Ebola Virus Ribonucleoprotein
      and Enhances Viral RNA Synthesis.
AB  - Ebola virus (EBOV) genome and mRNAs contain long, structured regions that could
      hijack host RNA-binding proteins to facilitate infection. We performed RNA
      affinity chromatography coupled with mass spectrometry to identify host proteins
      that bind to EBOV RNAs and identified four high-confidence proviral host factors,
      including Staufen1 (STAU1), which specifically binds both 3' and 5'
      extracistronic regions of the EBOV genome. We confirmed that EBOV infection rate
      and production of infectious particles were significantly reduced in STAU1
      depleted cells. STAU1 was recruited to sites of EBOV RNA synthesis upon infection
      and enhanced viral RNA synthesis. Furthermore, STAU1 interacts with EBOV
      nucleoprotein (NP), virion protein 30 (VP30), and VP35; the latter two bridge the
      viral polymerase to the NP-coated genome, forming the viral ribonucleoprotein
      (RNP) complex. Our data indicate that STAU1 plays a critical role in EBOV
      replication by coordinating interactions between the viral genome and RNA
      synthesis machinery.IMPORTANCE Ebola virus (EBOV) is a negative-strand RNA virus
      with significant public health importance. Currently, no therapeutics are
      available for Ebola, which imposes an urgent need for a better understanding of
      EBOV biology. Here we dissected the virus-host interplay between EBOV and host
      RNA-binding proteins. We identified novel EBOV host factors, including Staufen1,
      which interacts with multiple viral factors and is required for efficient viral
      RNA synthesis.

PMID- 30301859
TI  - Modernized Tools for Streamlined Genetic Manipulation and Comparative Study of
      Wild and Diverse Proteobacterial Lineages.
AB  - Correlating the presence of bacteria and the genes they carry with aspects of
      plant and animal biology is rapidly outpacing the functional characterization of
      naturally occurring symbioses. A major barrier to mechanistic studies is the lack
      of tools for the efficient genetic manipulation of wild and diverse bacterial
      isolates. To address the need for improved molecular tools, we used a collection
      of proteobacterial isolates native to the zebrafish intestinal microbiota as a
      testbed to construct a series of modernized vectors that expedite genetic knock
      in and knockout procedures across lineages. The innovations that we introduce
      enhance the flexibility of conventional genetic techniques, making it easier to
      manipulate many different bacterial isolates with a single set of tools. We
      developed alternative strategies for domestication-free conjugation, designed
      plasmids with customizable features, and streamlined allelic exchange using
      visual markers of homologous recombination. We demonstrate the potential of these
      tools through a comparative study of bacterial behavior within the zebrafish
      intestine. Live imaging of fluorescently tagged isolates revealed a spectrum of
      distinct population structures that differ in their biogeography and dominant
      growth mode (i.e., planktonic versus aggregated). Most striking, we observed
      divergent genotype-phenotype relationships: several isolates that are predicted
      by genomic analysis and in vitro assays to be capable of flagellar motility do
      not display this trait within living hosts. Together, the tools generated in this
      work provide a new resource for the functional characterization of wild and
      diverse bacterial lineages that will help speed the research pipeline from
      sequencing-based correlations to mechanistic underpinnings.IMPORTANCE A great
      challenge in microbiota research is the immense diversity of symbiotic bacteria
      with the capacity to impact the lives of plants and animals. Moving beyond
      correlative DNA sequencing-based studies to define the cellular and molecular
      mechanisms by which symbiotic bacteria influence the biology of their hosts is
      stalling because genetic manipulation of new and uncharacterized bacterial
      isolates remains slow and difficult with current genetic tools. Moreover,
      developing tools de novo is an arduous and time-consuming task and thus
      represents a significant barrier to progress. To address this problem, we
      developed a suite of engineering vectors that streamline conventional genetic
      techniques by improving postconjugation counterselection, modularity, and allelic
      exchange. Our modernized tools and step-by-step protocols will empower
      researchers to investigate the inner workings of both established and newly
      emerging models of bacterial symbiosis.

PMID- 30301862
TI  - Use mesh implants for stress urinary incontinence only as last resort, says NICE.

PMID- 30301863
TI  - Histone deacetylase inhibition has targeted clinical benefit in ARID1A mutated
      advanced urothelial carcinoma.
AB  - Histone deacetylase (HDAC) inhibition has sporadic clinical efficacy in
      urothelial carcinoma (UC); the genomic basis for clinical response is not known.
      In two separate phase I clinical trials testing pharmacokinetic aspects of HDAC
      inhibitors in advanced solid tumors, we identified one patient with advanced UC
      who had a complete response (CR) to belinostat, and one patient with advanced UC
      who had a partial response (PR) to panobinostat. The archived tumors of the
      responders were genomically characterized in comparison to others with UC on the
      trials. UC cell lines treated with panobinostat and belinostat were studied to
      elucidate the mechanisms of benefit. Notably, the UC tumors that responded to
      HDAC inhibition had ARID1A mutations. ARID1A mutations were also noted in the
      tumors of three patients who had stable disease as their best response to HDAC
      inhibition. Corroborating the basis of sensitivity, transcriptional profiling of
      platinum-resistant ARID1A-mutated HT1197 cells treated with panobinostat reveals
      negative enrichment for both cyto-proliferative (MYC and E2F targets) and DNA
      repair gene sets, and positive enrichment for TP53 and inflammatory gene sets.
      Our study identifies ARID1A loss as a basis for clinical response to pan HDAC
      inhibition and offers avenues for potential rational therapeutic combinations
      with HDAC inhibitors in advanced UC.

PMID- 30301860
TI  - Renal COP9 Signalosome Deficiency Alters CUL3-KLHL3-WNK Signaling Pathway.
AB  - BACKGROUND: The familial hyperkalemic hypertension (FHHt) cullin 3 (CUL3) mutant
      does not degrade WNK kinases normally, thereby leading to thiazide-sensitive Na
      Cl cotransporter (NCC) activation. CUL3 mutant (CUL3Delta9) does not bind
      normally to the COP9 signalosome (CSN), a deneddylase involved in regulating
      cullin-RING ligases. CUL3Delta9 also caused increased degradation of the CUL3-WNK
      substrate adaptor kelch-like 3 (KLHL3). Here, we sought to determine how
      defective CSN action contributes to the CUL3Delta9 phenotype. METHODS: The
      Pax8/LC1 mouse system was used to generate mice in which the catalytically active
      CSN subunit, Jab1, was deleted only along the nephron, after full development (KS
      Jab1 -/-). RESULTS: Western blot analysis demonstrated that Jab1 deletion
      increased the abundance of neddylated CUL3. Moreover, total CUL3 expression was
      reduced, suggesting decreased CUL3 stability. KLHL3 was almost completely absent
      in KS-Jab1 -/- mice. Conversely, the protein abundances of WNK1, WNK4, and SPAK
      kinases were substantially higher. Activation of WNK4, SPAK, and OSR1 was
      indicated by higher phosphorylated protein levels and translocation of the
      proteins into puncta, as observed by immunofluorescence. The ratio of
      phosphorylated NCC to total NCC was also higher. Surprisingly, NCC protein
      abundance was low, likely contributing to hypokalemia and Na+ and K+ wasting.
      Additionally, long-term Jab1 deletion resulted in kidney damage. CONCLUSIONS:
      Together, the results indicate that deficient CSN binding contributes importantly
      to the FHHt phenotype. Although defective CUL3Delta9-faciliated WNK4 degradation
      likely contributes, dominant effects on KLHL3 may be a second factor that is
      necessary for the phenotype.

PMID- 30301861
TI  - Combined Structural and Functional Imaging of the Kidney Reveals Major Axial
      Differences in Proximal Tubule Endocytosis.
AB  - BACKGROUND: The kidney proximal convoluted tubule (PCT) reabsorbs filtered
      macromolecules via receptor-mediated endocytosis (RME) or nonspecific fluid phase
      endocytosis (FPE); endocytosis is also an entry route for disease-causing toxins.
      PCT cells express the protein ligand receptor megalin and have a highly developed
      endolysosomal system (ELS). Two PCT segments (S1 and S2) display subtle
      differences in cellular ultrastructure; whether these translate into differences
      in endocytotic function has been unknown. METHODS: To investigate potential
      differences in endocytic function in S1 and S2, we quantified ELS protein
      expression in mouse kidney PCTs using real-time quantitative polymerase chain
      reaction and immunostaining. We also used multiphoton microscopy to visualize
      uptake of fluorescently labeled ligands in both living animals and tissue cleared
      using a modified CLARITY approach. RESULTS: Uptake of proteins by RME occurs
      almost exclusively in S1. In contrast, dextran uptake by FPE takes place in both
      S1 and S2, suggesting that RME and FPE are discrete processes. Expression of key
      ELS proteins, but not megalin, showed a bimodal distribution; levels were far
      higher in S1, where intracellular distribution was also more polarized. Tissue
      clearing permitted imaging of ligand uptake at single-organelle resolution in
      large sections of kidney cortex. Analysis of segmented tubules confirmed that,
      compared with protein uptake, dextran uptake occurred over a much greater length
      of the PCT, although individual PCTs show marked heterogeneity in solute uptake
      length and three-dimensional morphology. CONCLUSIONS: Striking axial differences
      in ligand uptake and ELS function exist along the PCT, independent of megalin
      expression. These differences have important implications for understanding
      topographic patterns of kidney diseases and the origins of proteinuria.

PMID- 30301865
TI  - Monitoring tumor burden in response to FOLFIRINOX chemotherapy via profiling
      circulating cell-free DNA in pancreatic cancer.
AB  - We aimed to explore the application of circulating cell-free DNA (cfDNA)
      profiling in monitoring tumor burden in patients with pancreatic ductal
      adenocarcinoma (PDAC). Thirty-eight advanced PDAC patients receiving first-line
      FOLFIRINOX chemotherapy were prospectively enrolled. Next-generation sequencing
      for a panel of 560 genes covering a wide range of cancer-related loci was
      performed to profile cfDNA. In total, twenty-five patients (65.8%) had at least
      one common driver gene alterations (KRAS, TP53, SMAD4, CDKN2A) detected within
      cfDNA. In contrast, no above tumor-related recurrent mutations were found in
      plasma from 13 healthy individuals. Concordant alterations in plasma cfDNA and
      tumor tissue DNA was confirmed in 2 out of 3 patients with available tissues.
      Further analysis showed that mutant allele fraction (MAF) for altered loci in
      cfDNA correlated with tumor stage, metastatic burden, and overall survival.
      Serial blood samples were collected from 17 patients after chemotherapy. We found
      that allele fraction for specific altered loci declined in chemotherapy
      responding subjects. For cases who were resistant to this therapeutic regimen,
      increased ctDNA MAF was observed at the time of disease progression. Meanwhile,
      the dynamics of total cfDNA concentration correlated with tumor burden following
      chemotherapy. Collectively, we provide evidence that pre-treatment ctDNA level
      correlates with tumor burden in PDAC, and serial cfDNA analysis is a robust tool
      for monitoring cancer response to chemotherapy.

PMID- 30301864
TI  - ODM-203 a selective inhibitor of FGFR and VEGFR, shows strong anti-tumor
      activity, and induces anti-tumor immunity.
AB  - Alterations in the gene encoding for the fibroblast growth factor receptor (FGFR)
      and upregulation of the vascular endothelial growth factor receptor (VEGFR) are
      found often in cancer, which correlate with disease progression and unfavorable
      survival. Additionally, FGFR and VEGFR signaling synergistically promote tumor
      angiogenesis, and activation of FGFR signaling has been described as functional
      compensatory angiogenic signal following development of resistance to VEGFR
      inhibition. Several selective small-molecule FGFR kinase inhibitors are currently
      in clinical development. ODM-203 is a novel, selective and equipotent inhibitor
      of the FGFR and VEGFR families. In this report we show that ODM-203 inhibits FGFR
      and VEGFR family kinases selectively and with equal potency in the low nanomolar
      range (IC50 6-35 nM) in biochemical assays. In cellular assays, ODM-203 inhibits
      VEGFR-induced tube formation (IC50 33 nM) with similar potency as it inhibits
      proliferation in FGFR-dependent cell lines (IC50 50-150 nM). In vivo, ODM-203
      shows strong anti-tumor activity in both FGFR-dependent xenograft models and in
      an angiogenic xenograft model at similar well-tolerated doses. In addition, ODM
      203 inhibits metastatic tumor growth in a highly angiogenesis-dependent kidney
      capsule syngenic model. Interestingly, potent anti-tumor activity in the
      subcutaneous syngenic model correlated well with immune modulation in the tumor
      microenvironment as indicated by marked decrease in the expression of immune
      check points PD-1 and PD-L1 on CD8 T cells and NK cells, and increased activation
      of CD8 T cells. In summary, ODM-203 shows equipotent activity for both FGFR and
      VEGFR kinase families and antitumor activity in both FGFR- and angigogenesis-
      models.

PMID- 30301866
TI  - Changing the cancer label: beware the euphemistic treadmill.

PMID- 30301867
TI  - Association between fine particulate matter and oral cancer among Taiwanese men.
AB  - The aim of this study was to investigate the association between fine particulate
      matter 2.5 (PM2.5) and oral cancer among Taiwanese men. Four linked data sources
      including the Taiwan Cancer Registry, Adult Preventive Medical Services Database,
      National Health Insurance Research Database, and Air Quality Monitoring Database
      were used. Concentrations of sulfur dioxide, carbon monoxide, ozone, NOx
      (nitrogen monoxide and nitrogen dioxide), coarse particulate matter (PM10-2.5)
      and PM2.5 in 2009 were assessed in quartiles. A total of 482 659 men aged 40
      years and above were included in the analysis. Logistic regression was used to
      examine the association between PM2.5 and oral cancer diagnosed from 2012 to
      2013. After adjusting for potential confounders, the ORs of oral cancer were 0.91
      (95% CI 0.75 to 1.11) for 26.74<=PM2.5<32.37, 1.01 (95% CI 0.84 to 1.20) for
      32.37<=PM2.5<40.37 ug/m3 and 1.43 (95% CI 1.17 to 1.74) for PM2.5>=40.37 ug/m3
      compared with PM2.5<26.74 ug/m3 In this study, there was an increased risk of
      oral cancer among Taiwanese men who were exposed to higher concentrations of
      PM2.5.

PMID- 30301868
TI  - Detection of endometrial precancer by a targeted gynecologic cancer liquid
      biopsy.
AB  - Endometrial cancer is the most common gynecologic malignancy in industrialized
      countries and both its incidence and associated mortality are increasing. The
      "liquid biopsy" is becoming an important transformative precision oncology tool
      but barriers intrinsic to blood sampling have limited its use in early cancer
      detection. We hypothesized that using a more targeted sample for analysis,
      namely, a uterine lavage, should provide a more sensitive and specific diagnostic
      test for endometrial cancer. Using a custom 12-gene endometrial cancer panel,
      molecular analysis of uterine lavage fluid from an asymptomatic 67-year-old
      female without histopathologic evidence of pre-malignant lesions or cancer in her
      uterine tissue, revealed two oncogenic PTEN mutations. Ten months later, the
      patient returned with postmenopausal bleeding and a single microscopic focus of
      endometrial cancer. DNA isolated and sequenced from laser-capture microdissected
      tumor tissue revealed the same two PTEN mutations. These mutations were unlikely
      to occur by chance alone (p<3x10-7). This illustrative case provides the first
      demonstration that future, tumor-specific mutations can be identified in an
      asymptomatic individual without clinical or pathologic evidence of cancer by
      using already established sequencing technologies but targeted sampling methods.
      This finding provides the basis for new opportunities in early cancer screening,
      detection and prevention.

PMID- 30301869
TI  - Nebulin increases thin filament stiffness and force per cross-bridge in slow
      twitch soleus muscle fibers.
AB  - Nebulin (Neb) is associated with the thin filament in skeletal muscle cells, but
      its functions are not well understood. For this goal, we study skinned slow
      twitch soleus muscle fibers from wild-type (Neb+) and conditional Neb knockout
      (Neb-) mice. We characterize cross-bridge (CB) kinetics and the elementary steps
      of the CB cycle by sinusoidal analysis during full Ca2+ activation and observe
      that Neb increases active tension 1.9-fold, active stiffness 2.7-fold, and rigor
      stiffness 3.0-fold. The ratio of stiffness during activation and rigor states is
      62% in Neb+ fibers and 68% in Neb- fibers. These are approximately proportionate
      to the number of strongly attached CBs during activation. Because the thin
      filament length is 15% shorter in Neb- fibers than in Neb+ fibers, the increase
      in force per CB in the presence of Neb is ~1.5 fold. The equilibrium constant of
      the CB detachment step (K 2), its rate (k 2), and the rate of the reverse force
      generation step (k -4) are larger in Neb+ fibers than in Neb- fibers. The rates
      of the force generation step (k 4) and the reversal detachment step (k -2) change
      in the opposite direction. These effects can be explained by Le Chatelier's
      principle: Increased CB strain promotes less force-generating state(s) and/or
      detached state(s). Further, when CB distributions among the six states are
      calculated, there is no significant difference in the number of strongly attached
      CBs between fibers with and without Neb. These results demonstrate that Neb
      increases force per CB. We also confirm that force is generated by isomerization
      of actomyosin (AM) from the AM.ADP.Pi state (ADP, adenosine diphophate; Pi,
      phosphate) to the AM*ADP.Pi state, where the same force is maintained after Pi
      release to result in the AM*ADP state. We propose that Neb changes the actin (and
      myosin) conformation for better ionic and hydrophobic/stereospecific AM
      interaction, and that the effect of Neb is similar to that of tropomyosin.

PMID- 30301871
TI  - Inner Workings: The mysterious parentage of the coveted black truffle.

PMID- 30301873
TI  - Sicker patients account for the weekend mortality effect among adult emergency
      admissions to a large hospital trust.
AB  - OBJECTIVE: To determine whether the higher weekend admission mortality risk is
      attributable to increased severity of illness. DESIGN: Retrospective analysis of
      4 years weekend and weekday adult emergency admissions to a university teaching
      hospital in England. OUTCOME MEASURES: 30-day postadmission weekend:weekday
      mortality ratios adjusted for severity of illness (baseline National Early
      Warning Score (NEWS)), routes of admission to hospital, transfer to the intensive
      care unit (ICU) and demographics. RESULTS: Despite similar emergency department
      daily attendance rates, fewer patients were admitted on weekends (mean admission
      rate 91/day vs 120/day) because of fewer general practitioner referrals. Weekend
      admissions were sicker than weekday (mean NEWS 1.8 vs 1.7, p=0.008), more likely
      to undergo transfer to ICU within 24 hours (4.2% vs 3.0%), spent longer in
      hospital (median 3 days vs 2 days) and less likely to experience same-day
      discharge (17.2% vs 21.9%) (all p values <0.001).The crude 30-day postadmission
      mortality ratio for weekend admission (OR=1.13; 95% CI 1.08 to 1.19) was
      attenuated using standard adjustment (OR=1.11; 95% CI 1.05 to 1.17). In patients
      for whom NEWS values were available (90%), the crude OR (1.07; 95% CI 1.01 to
      1.13) was not affected with standard adjustment. Adjustment using NEWS alone
      nullified the weekend effect (OR=1.02; 0.96-1.08).NEWS completion rates were
      higher on weekends (91.7%) than weekdays (89.5%). Missing NEWS was associated
      with direct transfer to intensive care bypassing electronic data capture. Missing
      NEWS in non-ICU weekend patients was associated with a higher mortality and fewer
      same-day discharges than weekdays. CONCLUSIONS: Patients admitted to hospital on
      weekends are sicker than those admitted on weekdays. The cause of the weekend
      effect may lie in community services.

PMID- 30301874
TI  - Impact of decision aids used during clinical encounters on clinician outcomes and
      consultation length: a systematic review.
AB  - BACKGROUND: Clinicians' satisfaction with encounter decision aids is an important
      component in facilitating implementation of these tools. We aimed to determine
      the impact of decision aids supporting shared decision making (SDM) during the
      clinical encounter on clinician outcomes. METHODS: We searched nine databases
      from inception to June 2017. Randomised clinical trials (RCTs) of decision aids
      used during clinical encounters with an unaided control group were eligible for
      inclusion. Due to heterogeneity among included studies, we used a narrative
      evidence synthesis approach. RESULTS: Twenty-five papers met inclusion criteria
      including 22 RCTs and 3 qualitative or mixed-methods studies nested in an RCT,
      together representing 23 unique trials. These trials evaluated healthcare
      decisions for cardiovascular prevention and treatment (n=8), treatment of
      diabetes mellitus (n=3), treatment of osteoporosis (n=2), treatment of depression
      (n=2), antibiotics to treat acute respiratory infections (n=3), cancer prevention
      and treatment (n=4) and prenatal diagnosis (n=1). Clinician outcomes were
      measured in only a minority of studies. Clinicians' satisfaction with decision
      making was assessed in only 8 (and only 2 of them showed statistically
      significantly greater satisfaction with the decision aid); only three trials
      asked if clinicians would recommend the decision aid to colleagues and only five
      asked if clinicians would use decision aids in the future. Outpatient
      consultations were not prolonged when a decision aid was used in 9 out of 13
      trials. The overall strength of the evidence was low, with the major risk of bias
      related to lack of blinding of participants and/or outcome assessors. CONCLUSION:
      Decision aids can improve clinicians' satisfaction with medical decision making
      and provide helpful information without affecting length of consultation time.
      Most SDM trials, however, omit outcomes related to clinicians' perspective on the
      decision making process or the likelihood of using a decision aid in the future.

PMID- 30301870
TI  - Kinetic properties of persistent Na+ current orchestrate oscillatory bursting in
      respiratory neurons.
AB  - The rhythmic pattern of breathing depends on the pre-Botzinger complex (preBotC)
      in the brainstem, a vital circuit that contains a population of neurons with
      intrinsic oscillatory bursting behavior. Here, we investigate the specific
      kinetic properties that enable voltage-gated sodium channels to establish
      oscillatory bursting in preBotC inspiratory neurons, which exhibit an unusually
      large persistent Na+ current (INaP). We first characterize the kinetics of INaP
      in neonatal rat brainstem slices in vitro, using whole-cell patch-clamp and
      computational modeling, and then test the contribution of INaP to rhythmic
      bursting in live neurons, using the dynamic clamp technique. We provide evidence
      that subthreshold activation, persistence at suprathreshold potentials, slow
      inactivation, and slow recovery from inactivation are kinetic features of INaP
      that regulate all aspects of intrinsic rhythmic bursting in preBotC neurons. The
      slow and cumulative inactivation of INaP during the burst active phase controls
      burst duration and termination, while the slow recovery from inactivation
      controls the duration of the interburst interval. To demonstrate this mechanism,
      we develop a Markov state model of INaP that explains a comprehensive set of
      voltage clamp data. By adding or subtracting a computer-generated INaP from a
      live neuron via dynamic clamp, we are able to convert nonbursters into intrinsic
      bursters, and vice versa. As a control, we test a model with inactivation
      features removed. Adding noninactivating INaP into nonbursters results in a
      pattern of random transitions between sustained firing and quiescence. The
      relative amplitude of INaP is the key factor that separates intrinsic bursters
      from nonbursters and can change the fraction of intrinsic bursters in the
      preBotC. INaP could thus be an important target for regulating network
      rhythmogenic properties.

PMID- 30301875
TI  - Non-Surgical Management of Colo-Colonic Intussusception in Patients with
      Hereditary Angioedema.
AB  - BACKGROUND Hereditary angioedema (HAE) is an autosomal disease caused either by
      deficiency or presence of a non-functioning C1 inhibitor. The lack or non
      functionality of said inhibitors leads to activation of an inflammatory cascade,
      which result in cutaneous and mucosal edema. Most patients with HAE present with
      either cutaneous, laryngeal/pharyngeal, or gastrointestinal exacerbations. An
      uncommon gastrointestinal manifestation of HAE is an intussusception, which in
      most cases require invasive/surgical management. CASE REPORT A 17-year-old
      Hispanic female patient with past medical history of HAE, presented with a 4-day
      history of episodic abdominal pain, worsening during the last 2 days with
      associated nausea, vomiting, and bright red blood per rectum. The abdominal
      ultrasound performed at our institution showed an elongated region of hypoechoic
      and hyperechoic concentric rings, raising suspicion of an intussusception. The
      patient was treated conservatively, with 30 mg of ecallantide and a unit of fresh
      frozen plasma (FFP). Follow-up abdominopelvic computed tomography scan was
      performed approximately 20 hours after the administration of fresh frozen plasma
      revealing complete interval resolution of the colo-colonic intussusception.
      Subsequently, the patient was kept under hospital care for the next 4 days with
      adequate progression of diet and without recurrence of intussusception.
      CONCLUSIONS To the best of our knowledge, most cases of patient with HAE
      presenting with intussusception have been treated with invasive/surgical
      procedures. In our case, conservative management has proven successful to reduce
      edema with subsequent non-surgical reduction of the intussusception. By directly
      targeting the pathophysiologic aspects of HAE, an unnecessary invasive procedure,
      as well as its potential complications, were avoided.

PMID- 30301876
TI  - Activation of Pelvic Floor Muscle During Ankle Posture Change on the Basis of a
      Three-Dimensional Motion Analysis System.
AB  - BACKGROUND Weak pelvic floor muscles (PFMs) is an important cause of stress
      urinary incontinence. Effective strengthening of PFMs is very helpful in
      improving lower urinary tract disease. The purpose of this study was to determine
      the activation of PFMs in accordance with movement of the pelvis and ankle.
      MATERIAL AND METHODS Fifty healthy adults who underwent PFM contraction in ankle
      posture change (dorsiflexion, neutral, and plantar flexion) while standing were
      simultaneously measured using electromyography and motion capture systems. Muscle
      activity at the tibialis anterior and gastrocnemius muscles was measured by
      surface electromyography electrodes and PFMs was measured using anal/vaginal
      probe. Motion analysis was captured by 3-dimensional motion trajectories of the
      retro-reflective markers. RESULTS At the ankle dorsiflexion, pelvic tilted
      anteriorly and PFMs were activated, but there was no pelvic movement in ankle
      plantar flexion. Significantly greater PFM activities were seen in ankle
      dorsiflexion. CONCLUSIONS PFM exercises performed in active ankle dorsiflexion
      positions while standing may increase the effectiveness of these exercises. For
      an effective pelvic floor enhancement in patients with weak PFMs, we recommend a
      dorsiflexion of the ankle in the standing position.

PMID- 30301877
TI  - Loss of TNFAIP3 enhances MYD88L265P-driven signaling in non-Hodgkin lymphoma.
AB  - MYD88 mutations are one of the most recurrent mutations in hematologic
      malignancies. However, recent mouse models suggest that MYD88L265P alone may not
      be sufficient to induce tumor formation. Interplay between MYD88L265P and other
      genetic events is further supported by the fact that TNFAIP3 (A20) inactivation
      often accompanies MYD88L265P. However, we are still lacking information about the
      consequence of MYD88L265P in combination with TNFAIP3 loss in human B cell
      lymphoma. Review of our genetic data on diffuse large B cell lymphoma (DLBCL) and
      Waldenstrom macroglobulinemia (WM), found that a large percentage of DLBCL and WM
      cases that have a MYD88 mutation also harbor a TNFAIP3 loss, 55% DLBCL and 28% of
      WM, respectively. To mimic this combination of genetic events, we used genomic
      editing technology to knock out TNFAIP3 in MYD88L265P non-Hodgkin's lymphoma
      (NHL) cell lines. Loss of A20 expression resulted in increased NF-kappaB and p38
      activity leading to upregulation of the NF-kappaB target genes BCL2 and MYC.
      Furthermore, we detected the increased production of IL-6 and CXCL10 which led to
      an upregulation of the JAK/STAT pathway. Overall, these results suggest that
      MYD88L265P signaling can be enhanced by a second genetic alteration in TNFAIP3
      and highlights a potential opportunity for therapeutic targeting.

PMID- 30301878
TI  - Circadian rhythms and psychiatric profiles in young adults with unipolar
      depressive disorders.
AB  - Abnormalities in circadian rhythms have been reported in people with mood
      disorders, but these abnormalities are marked by considerable inter-individual
      variability. This study aimed to identify pathophysiological subgroups on the
      basis of circadian markers and evaluate how these subgroups relate to psychiatric
      profiles. Thirty-five young adults (18-31 years old) receiving clinical care for
      unipolar depressive disorders and 15 healthy controls took part to this study.
      The Hamilton Rating Scale for Depression and the Young Mania rating scale were
      used to evaluate the severity of mood symptoms in participants with depressive
      disorders. All participant underwent ambulatory sleep monitoring with actigraphy
      for about 12 days before attending a laboratory-based chronobiological assessment
      which included repeated salivary samples to determine dim light melatonin onset
      (DLMO) and continuous core body temperature (CBT) monitoring using an ingestible
      temperature sensor. Cluster analyses were conducted across all participants to
      identify subgroups with consistent circadian timing profiles based on DLMO and
      the nocturnal minima of CBT. Two clusters were identified: 'delayed' and
      'conventional timing' circadian phase. Descriptive analyses showed that the
      delayed cluster was characterised by abnormal time relationships between
      circadian phase markers and the sleep-wake cycle. Importantly, individuals from
      the delayed cluster had worse depression severity (t(28) = -2.7, p = 0.011) and
      hypomanic symptoms (Z = -2.2, p = 0.041) than their peers with conventional
      circadian timing. These findings suggest that delayed and disorganised circadian
      rhythms may be linked to worse psychiatric profiles in young people with
      depressive disorders.

PMID- 30301879
TI  - Schizophrenia-related cognitive dysfunction in the Cyclin-D2 knockout mouse model
      of ventral hippocampal hyperactivity.
AB  - Elevated activity at the output stage of the anterior hippocampus has been
      described as a physiological endophenotype of schizophrenia, and its development
      maps onto the transition from the prodromal to the psychotic state. Interventions
      that halt the spreading glutamatergic over-activity in this region and thereby
      the development of overt schizophrenia could be promising therapies. However,
      animal models with high construct validity to support such pre-clinical
      development are scarce. The Cyclin-D2 knockout (CD2-KO) mouse model shows a
      hippocampal parvalbumin-interneuron dysfunction, and its pattern of hippocampal
      over-activity shares similarities with that seen in prodromal patients.
      Conducting a comprehensive phenotyping of CD2-KO mice, we found that they
      displayed novelty-induced hyperlocomotion (a rodent correlate of positive
      symptoms of schizophrenia), that was largely resistant against D1- and D2
      dopamine-receptor antagonism, but responsive to the mGluR2/3-agonist LY379268. In
      the negative symptom domain, CD2-KO mice showed transiently reduced sucrose
      preference (anhedonia), but enhanced interaction with novel mice and objects, as
      well as normal nest building and incentive motivation. Also, unconditioned
      anxiety, perseveration, and motor-impulsivity were unaltered. However, in the
      cognitive domain, CD2-knockouts showed reduced executive function in assays of
      rule-shift and rule-reversal learning, and also an impairment in working memory,
      that was resistant against LY379268-treatment. In contrast, sustained attention
      and forms of spatial and object-related memory that are mediated by short-term
      habituation of stimulus-specific attention were intact. Our results suggest that
      CD2-KO mice are a valuable model in translational research targeted at the
      pharmacoresistant cognitive symptom domain in causal relation to hippocampal over
      activity in the prodrome-to-psychosis transition.

PMID- 30301880
TI  - Dengue virus and the host innate immune response.
AB  - Dengue virus (DENV) is a mosquito-borne Flavivirus that is endemic in many
      tropical and sub-tropical countries where the transmission vectors Aedes spp.
      mosquitoes resides. There are four serotypes of the virus. Each serotype is
      antigenically different, meaning they elicit heterologous antibodies. Infection
      with one serotype will create neutralizing antibodies to the serotype. Cross
      protection from other serotypes is not long term, instead heterotypic infection
      can cause severe disease. This review will focus on the innate immune response to
      DENV infection and the virus evasion of the innate immune system by escaping
      recognition or inhibiting the production of an antiviral state. Activated innate
      immune pathways includes type I interferon, complement, apoptosis, and autophagy,
      which the virus can evade or exploit to exacerbate disease. It is important to
      understand out how the immune system reacts to infection and how the virus evades
      immune response in order to develop effective antivirals and vaccines.

PMID- 30301881
TI  - Apatinib-induced protective autophagy and apoptosis through the AKT-mTOR pathway
      in anaplastic thyroid cancer.
AB  - Apatinib, an inhibitor of vascular endothelial growth factor receptor-2, has been
      shown to promote anti-cancer action across a wide range of malignancies,
      including gastric, lung, and breast cancers. Our previous study showed that
      apatinib increases apoptosis in anaplastic thyroid carcinoma (ATC), but the
      direct functional mechanism of tumor lethality mediated by apatinib is still
      unknown. In this study, we demonstrated that apatinib induced both autophagy and
      apoptosis in human ATC cells through downregulation of p-AKT and p-mTOR signals
      via the AKT/mTOR pathway. Moreover, inhibition of apatinib-induced autophagy
      increased apatinib-induced apoptosis in ATC cells, and additional tumor
      suppression was critically produced by the combination of apatinib and the
      autophagy inhibitor chloroquine in vivo and in vitro. These findings showed that
      both autophagy and AKT/mTOR signals were engaged in ATC cell death evoked by
      apatinib. ATC patients might benefit from the new anti-cancer drug, and molecular
      targeted treatment in combination with autophagy inhibitors shows promise as a
      treatment improvement.

PMID- 30301882
TI  - Role of apurinic/apyrimidinic nucleases in the regulation of homologous
      recombination in myeloma: mechanisms and translational significance.
AB  - We have previously reported that homologous recombination (HR) is dysregulated in
      multiple myeloma (MM) and contributes to genomic instability and development of
      drug resistance. We now demonstrate that base excision repair (BER) associated
      apurinic/apyrimidinic (AP) nucleases (APEX1 and APEX2) contribute to regulation
      of HR in MM cells. Transgenic as well as chemical inhibition of APEX1 and/or
      APEX2 inhibits HR activity in MM cells, whereas the overexpression of either
      nuclease in normal human cells, increases HR activity. Regulation of HR by AP
      nucleases could be attributed, at least in part, to their ability to regulate
      recombinase (RAD51) expression. We also show that both nucleases interact with
      major HR regulators and that APEX1 is involved in P73-mediated regulation of
      RAD51 expression in MM cells. Consistent with the role in HR, we also show that
      AP-knockdown or treatment with inhibitor of AP nuclease activity increases
      sensitivity of MM cells to melphalan and PARP inhibitor. Importantly, although
      inhibition of AP nuclease activity increases cytotoxicity, it reduces genomic
      instability caused by melphalan. In summary, we show that APEX1 and APEX2, major
      BER proteins, also contribute to regulation of HR in MM. These data provide basis
      for potential use of AP nuclease inhibitors in combination with chemotherapeutics
      such as melphalan for synergistic cytotoxicity in MM.

PMID- 30301883
TI  - Mitochondrial fusion and Bid-mediated mitochondrial apoptosis are perturbed by
      alcohol with distinct dependence on its metabolism.
AB  - Environmental stressors like ethanol (EtOH) commonly target mitochondria to
      influence the cell's fate. Recent literature supports that chronic EtOH exposure
      suppresses mitochondrial dynamics, central to quality control, and sensitizes
      mitochondrial permeability transition pore opening to promote cell death. EtOH
      induced tissue injury is primarily attributed to its toxic metabolic products but
      alcoholism also impairs tissues that poorly metabolize EtOH. We embarked on
      studies to determine the respective roles of EtOH and its metabolites in
      mitochondrial fusion and tBid-induced mitochondrial apoptosis. We used HepG2
      cells that do not metabolize EtOH and its engineered clone that expresses EtOH
      metabolizing Cytochrome P450 E2 and alcohol dehydrogenase (VL-17A cells). We
      found that fusion impairment by prolonged EtOH exposure was prominent in VL-17A
      cells, probably owing to reactive oxygen species increase in the mitochondrial
      matrix. There was no change in fusion protein abundance, mitochondrial membrane
      potential or Ca2+ uptake. By contrast, prolonged EtOH exposure promoted tBid
      induced outer mitochondrial membrane permeabilization and cell death only in
      HepG2 cells, owing to enhanced Bak oligomerization. Thus, mitochondrial fusion
      inhibition by EtOH is dependent on its metabolites, whereas sensitization to tBid
      induced death is mediated by EtOH itself. This difference is of
      pathophysiological relevance because of the tissue-specific differences in EtOH
      metabolism.

PMID- 30301884
TI  - Patchwork of contrasting medication cultures across the USA.
AB  - Health in the United States is markedly heterogeneous, with large disparities in
      disease incidence, treatment choices and health spending. Drug prescription is
      one major component of health care-reflecting the accuracy of diagnosis, the
      adherence to evidence-based guidelines, susceptibility to drug marketing and
      regulatory factors. Using medical claims data covering nearly half of the USA
      population, we have developed and validated a framework to compare prescription
      rates of 600 popular drugs in 2334 counties. Our approach uncovers geographically
      separated sub-Americas, where patients receive treatment for different diseases,
      and where physicians choose different drugs for the same disease. The
      geographical variation suggests influences of racial composition, state-level
      health care laws and wealth. Some regions consistently prefer more expensive
      drugs, even when they have not been proven more efficacious than cheaper
      alternatives. Our study underlines the benefit of aggregating massive information
      on medical practice into a summarized and actionable form.

PMID- 30301885
TI  - Metastatic adrenocortical carcinoma displays higher mutation rate and tumor
      heterogeneity than primary tumors.
AB  - Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and high
      mortality due to metastatic disease. All reported genetic alterations have been
      in primary ACC, and it is unknown if there is molecular heterogeneity in ACC.
      Here, we report the genetic changes associated with metastatic ACC compared to
      primary ACCs and tumor heterogeneity. We performed whole-exome sequencing of 33
      metastatic tumors. The overall mutation rate (per megabase) in metastatic tumors
      was 2.8-fold higher than primary ACC tumor samples. We found tumor heterogeneity
      among different metastatic sites in ACC and discovered recurrent mutations in
      several novel genes. We observed 37-57% overlap in genes that are mutated among
      different metastatic sites within the same patient. We also identified new
      therapeutic targets in recurrent and metastatic ACC not previously described in
      primary ACCs.

PMID- 30301886
TI  - Alpha-fetoprotein inhibits autophagy to promote malignant behaviour in
      hepatocellular carcinoma cells by activating PI3K/AKT/mTOR signalling.
AB  - Alpha-fetoprotein (AFP) has been recognized as a key regulator of cell
      proliferation in hepatocellular carcinoma (HCC). However, whether AFP functions
      in cancer cell autophagy remains unknown. This study investigated the effects of
      AFP on autophagy in HCC cells. The role of AFP was studied in two HCC cell lines,
      PLC/PRF/5 and HLE. Cell autophagy, apoptosis, proliferation, migration and
      invasion were analysed with Western blotting, co-immunoprecipitation (CoIP),
      immunofluorescence, animal models, MTT assays, flow cytometry (FCM), Cell
      Counting Kit (CCK)-8, and scratch and transwell assays. In PLC/PRF/5 cells, AFP
      interacted with PTEN and activated PI3K/Akt/mTOR signalling. In HLE cells,
      overexpressed AFP similarly interacted with PTEN, leading to PI3K/Akt/mTOR
      activation and reduced cell autophagy. When AFP was silenced in PLC/PRF/5 cells,
      cell proliferation, tumour growth, migration and invasion were inhibited, and the
      numbers of S-phase and apoptotic cells were increased. In contrast, AFP
      overexpression in HLE cells enhanced cell proliferation, migration and invasion
      and reduced apoptosis. AFP-dependent autophagy, proliferation, migration and
      apoptosis were inhibited by rapamycin. In summary, AFP plays critical roles in
      the inhibition of autophagy and apoptosis in HCC cells and promotes
      proliferation, migration and invasion. The role of AFP in autophagy inhibition in
      HCC cells may involve the activation of PI3K/Akt/mTOR signalling.

PMID- 30301889
TI  - Primary care cohort study in the sequence of diagnosing chronic respiratory
      diseases and prescribing inhaled corticosteroids.
AB  - To prevent unnecessary use of inhaled corticosteroids (ICS), ICS treatment should
      only be started when the diagnostic process of asthma and COPD is completed.
      Little is known about the chronological order between these diagnoses and the
      start of ICS. We performed a retrospective cohort study, based on electronic
      medical records of 178 Dutch general practices, to explore the temporal relations
      between starting continuous use of ICS and receiving a diagnosis of asthma and/or
      COPD. The database included information of patients who were registered with a
      diagnosis of asthma and/or COPD in one of the practices during January 1, 2012
      and December 31, 2013. Two or more successive prescriptions of ICS within 6
      months were considered as continuous ICS treatment. The chronological order of
      events based on available dates were analysed using descriptive analyses. For
      8507 patients with asthma, 4024 patients with COPD, and 801 patients with asthma
      COPD overlap (ACO), the order of events could be analysed. In total, 1857 (14.4%)
      patients started ICS prior to their diagnosis, 11.5, 20.8, and 10.0% of patients
      with asthma, COPD, and ACO, respectively. In 53.4% of the patients, the first
      prescription of ICS was a combination inhaler with a long-acting bronchodilator.
      In this real-life primary care cohort, one in seven patients started ICS
      treatment prior to their diagnosis and approximately half of the patients started
      with a combination inhaler. Our findings suggest that there is relevant room for
      improvement in the pharmaceutical management of patients with these chronic
      respiratory diseases.

PMID- 30301887
TI  - Loss of pyruvate kinase M2 limits growth and triggers innate immune signaling in
      endothelial cells.
AB  - Despite their inherent proximity to circulating oxygen and nutrients, endothelial
      cells (ECs) oxidize only a minor fraction of glucose in mitochondria, a metabolic
      specialization that is poorly understood. Here we show that the glycolytic enzyme
      pyruvate kinase M2 (PKM2) limits glucose oxidation, and maintains the growth and
      epigenetic state of ECs. We find that loss of PKM2 alters mitochondrial substrate
      utilization and impairs EC proliferation and migration in vivo. Mechanistically,
      we show that the NF-kappaB transcription factor RELB is responsive to PKM2 loss,
      limiting EC growth through the regulation of P53. Furthermore, S
      adenosylmethionine synthesis is impaired in the absence of PKM2, resulting in DNA
      hypomethylation, de-repression of endogenous retroviral elements (ERVs) and
      activation of antiviral innate immune signalling. This work reveals the metabolic
      and functional consequences of glucose oxidation in the endothelium, highlights
      the importance of PKM2 for endothelial growth and links metabolic dysfunction
      with autoimmune activation in ECs.

PMID- 30301888
TI  - Microglia innately develop within cerebral organoids.
AB  - Cerebral organoids are 3D stem cell-derived models that can be utilized to study
      the human brain. The current consensus is that cerebral organoids consist of
      cells derived from the neuroectodermal lineage. This limits their value and
      applicability, as mesodermal-derived microglia are important players in neural
      development and disease. Remarkably, here we show that microglia can innately
      develop within a cerebral organoid model and display their characteristic
      ramified morphology. The transcriptome and response to inflammatory stimulation
      of these organoid-grown microglia closely mimic the transcriptome and response of
      adult microglia acutely isolated from post mortem human brain tissue. In
      addition, organoid-grown microglia mediate phagocytosis and synaptic material is
      detected inside them. In all, our study characterizes a microglia-containing
      organoid model that represents a valuable tool for studying the interplay between
      microglia, macroglia, and neurons in human brain development and disease.

PMID- 30301890
TI  - Physical descriptor for the Gibbs energy of inorganic crystalline solids and
      temperature-dependent materials chemistry.
AB  - The Gibbs energy, G, determines the equilibrium conditions of chemical reactions
      and materials stability. Despite this fundamental and ubiquitous role, G has been
      tabulated for only a small fraction of known inorganic compounds, impeding a
      comprehensive perspective on the effects of temperature and composition on
      materials stability and synthesizability. Here, we use the SISSO (sure
      independence screening and sparsifying operator) approach to identify a simple
      and accurate descriptor to predict G for stoichiometric inorganic compounds with
      ~50 meV atom-1 (~1 kcal mol-1) resolution, and with minimal computational cost,
      for temperatures ranging from 300-1800 K. We then apply this descriptor to
      ~30,000 known materials curated from the Inorganic Crystal Structure Database
      (ICSD). Using the resulting predicted thermochemical data, we generate thousands
      of temperature-dependent phase diagrams to provide insights into the effects of
      temperature and composition on materials synthesizability and stability and to
      establish the temperature-dependent scale of metastability for inorganic
      compounds.

PMID- 30301892
TI  - Interface-mediated hygroelectric generator with an output voltage approaching 1.5
      volts.
AB  - Hygroelectricity is proposed as a means to produce electric power from air by
      absorbing gaseous or vaporous water molecules, which are ubiquitous in the
      atmosphere. Here, using a synergy between a hygroscopic bulk graphene oxide with
      a heterogeneous structure and interface mediation between electrodes/materials
      with Schottky junctions, we develop a high-performance hygroelectric generator
      unit with an output voltage approaching 1.5 V. High voltage (e.g., 18 V with 15
      units) can be easily reached by simply scaling up the number of hygroelectric
      generator units in series, enough to drive commercial electronic devices. This
      work provides insight for the design and development of hygroelectric generators
      that may promote the efficient conversion of potential energy in the
      environmental atmosphere to electricity for practical applications.

PMID- 30301891
TI  - A genetic network mediating the control of bud break in hybrid aspen.
AB  - In boreal and temperate ecosystems, temperature signal regulates the reactivation
      of growth (bud break) in perennials in the spring. Molecular basis of temperature
      mediated control of bud break is poorly understood. Here we identify a genetic
      network mediating the control of bud break in hybrid aspen. The key components of
      this network are transcription factor SHORT VEGETATIVE PHASE-LIKE (SVL), closely
      related to Arabidopsis floral repressor SHORT VEGETATIVE PHASE, and its
      downstream target TCP18, a tree homolog of a branching regulator in Arabidopsis.
      SVL and TCP18 are downregulated by low temperature. Genetic evidence demonstrates
      their role as negative regulators of bud break. SVL mediates bud break by
      antagonistically acting on gibberellic acid (GA) and abscisic acid (ABA)
      pathways, which function as positive and negative regulators of bud break,
      respectively. Thus, our results reveal the mechanistic basis for temperature-cued
      seasonal control of a key phenological event in perennial plants.

PMID- 30301893
TI  - Meta-analysis of effects of exclusive breastfeeding on infant gut microbiota
      across populations.
AB  - Previous studies on the differences in gut microbiota between exclusively
      breastfed (EBF) and non-EBF infants have provided highly variable results. Here
      we perform a meta-analysis of seven microbiome studies (1825 stool samples from
      684 infants) to compare the gut microbiota of non-EBF and EBF infants across
      populations. In the first 6 months of life, gut bacterial diversity, microbiota
      age, relative abundances of Bacteroidetes and Firmicutes, and predicted microbial
      pathways related to carbohydrate metabolism are consistently higher in non-EBF
      than in EBF infants, whereas relative abundances of pathways related to lipid
      metabolism, vitamin metabolism, and detoxification are lower. Variation in
      predicted microbial pathways associated with non-EBF infants is larger among
      infants born by Caesarian section than among those vaginally delivered. Longer
      duration of exclusive breastfeeding is associated with reduced diarrhea-related
      gut microbiota dysbiosis. Furthermore, differences in gut microbiota between EBF
      and non-EBF infants persist after 6 months of age. Our findings elucidate some
      mechanisms of short and long-term benefits of exclusive breastfeeding across
      different populations.

PMID- 30301894
TI  - Stabilizing black phosphorus nanosheets via edge-selective bonding of sacrificial
      C60 molecules.
AB  - Few-layer black phosphorus (BP) with an anisotropic two-dimensional (2D)-layered
      structure shows potential applications in photoelectric conversion and
      photocatalysis, but is easily oxidized under ambient condition preferentially at
      its edge sites. Improving the ambient stability of BP nanosheets has been
      fulfilled by chemical functionalization, however this functionalization is
      typically non-selective. Here we show that edge-selective functionalization of BP
      nanosheets by covalently bonding stable C60 molecules leads to its significant
      stability improvement. Owing to the high stability of the hydrophobic C60
      molecule, C60 functions as a sacrificial shield and effectively protects BP
      nanosheets from oxidation under ambient condition. C60 bonding leads to a rapid
      photoinduced electron transfer from BP to C60, affording enhanced
      photoelectrochemical and photocatalytic activities. The selective passivation of
      the reactive edge sites of BP nanosheets by sacrificial C60 molecules paves the
      way toward ambient processing and applications of BP.

PMID- 30301896
TI  - Unravelling the structure of glycosyl cations via cold-ion infrared spectroscopy.
AB  - Glycosyl cations are the key intermediates during the glycosylation reaction that
      covalently links building blocks during the synthetic assembly of carbohydrates.
      The exact structure of these ions remained elusive due to their transient and
      short-lived nature. Structural insights into the intermediate would improve our
      understanding of the reaction mechanism of glycosidic bond formation. Here, we
      report an in-depth structural analysis of glycosyl cations using a combination of
      cold-ion infrared spectroscopy and first-principles theory. Participating C2
      protective groups form indeed a covalent bond with the anomeric carbon that leads
      to C1-bridged acetoxonium-type structures. The resulting bicyclic structure
      strongly distorts the ring, which leads to a unique conformation for each
      individual monosaccharide. This gain in mechanistic understanding fundamentally
      impacts glycosynthesis and will allow to tailor building blocks and reaction
      conditions in the future.

PMID- 30301895
TI  - Genetic signature to provide robust risk assessment of psoriatic arthritis
      development in psoriasis patients.
AB  - Psoriatic arthritis (PsA) is a complex chronic musculoskeletal condition that
      occurs in ~30% of psoriasis patients. Currently, no systematic strategy is
      available that utilizes the differences in genetic architecture between PsA and
      cutaneous-only psoriasis (PsC) to assess PsA risk before symptoms appear. Here,
      we introduce a computational pipeline for predicting PsA among psoriasis patients
      using data from six cohorts with >7000 genotyped PsA and PsC patients. We
      identify 9 new loci for psoriasis or its subtypes and achieve 0.82 area under the
      receiver operator curve in distinguishing PsA vs. PsC when using 200 genetic
      markers. Among the top 5% of our PsA prediction we achieve >90% precision with
      100% specificity and 16% recall for predicting PsA among psoriatic patients,
      using conditional inference forest or shrinkage discriminant analysis. Combining
      statistical and machine-learning techniques, we show that the underlying genetic
      differences between psoriasis subtypes can be used for individualized subtype
      risk assessment.

PMID- 30301897
TI  - Two-site H2O2 photo-oxidation on haematite photoanodes.
AB  - H2O2 is a sacrificial reductant that is often used as a hole scavenger to gain
      insight into photoanode properties. Here we show a distinct mechanism of H2O2
      photo-oxidation on haematite (alpha-Fe2O3) photoanodes. We found that the
      photocurrent voltammograms display non-monotonous behaviour upon varying the H2O2
      concentration, which is not in accord with a linear surface reaction mechanism
      that involves a single reaction site as in Eley-Rideal reactions. We postulate a
      nonlinear kinetic mechanism that involves concerted interaction between adions
      induced by H2O2 deprotonation in the alkaline solution with adjacent intermediate
      species of the water photo-oxidation reaction, thereby involving two reaction
      sites as in Langmuir-Hinshelwood reactions. The devised kinetic model reproduces
      our main observations and predicts coexistence of two surface reaction paths (bi
      stability) in a certain range of potentials and H2O2 concentrations. This
      prediction is confirmed experimentally by observing a hysteresis loop in the
      photocurrent voltammogram measured in the predicted coexistence range.

PMID- 30301898
TI  - Cryo-EM structure of the hibernating Thermus thermophilus 100S ribosome reveals a
      protein-mediated dimerization mechanism.
AB  - In response to cellular stresses bacteria conserve energy by dimerization of
      ribosomes into inactive hibernating 100S ribosome particles. Ribosome
      dimerization in Thermus thermophilus is facilitated by hibernation-promoting
      factor (TtHPF). In this study we demonstrate high sensitivity of Tt100S formation
      to the levels of TtHPF and show that a 1:1 ratio leads to optimal dimerization.
      We report structures of the T. thermophilus 100S ribosome determined by cryo
      electron microscopy to average resolutions of 4.13 A and 4.57 A. In addition, we
      present a 3.28 A high-resolution cryo-EM reconstruction of a 70S ribosome from a
      hibernating ribosome dimer and reveal a role for the linker region connecting the
      TtHPF N- and C-terminal domains in translation inhibition by preventing Shine
      Dalgarno duplex formation. Our work demonstrates that species-specific
      differences in the dimerization interface govern the overall conformation of the
      100S ribosome particle and that for Thermus thermophilus no ribosome-ribosome
      interactions are involved in the interface.

PMID- 30301899
TI  - A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social
      memory dynamics.
AB  - Recent results suggest that social memory requires the dorsal hippocampal CA2
      region as well as a subset of ventral CA1 neurons. However, it is unclear whether
      dorsal CA2 and ventral CA1 represent parallel or sequential circuits. Moreover,
      because evidence implicating CA2 in social memory comes largely from long-term
      inactivation experiments, the dynamic role of CA2 in social memory remains
      unclear. Here, we use pharmacogenetics and optogenetics in mice to acutely and
      reversibly silence dorsal CA2 and its projections to ventral hippocampus. We show
      that dorsal CA2 activity is critical for encoding, consolidation, and recall
      phases of social memory. Moreover, dorsal CA2 contributes to social memory by
      providing strong excitatory input to the same subregion of ventral CA1 that
      contains the subset of neurons implicated in social memory. Thus, our studies
      provide new insights into a dorsal CA2 to ventral CA1 circuit whose dynamic
      activity is necessary for social memory.

PMID- 30301900
TI  - Understanding the transfer reaction network behind the non-processive synthesis
      of low molecular weight levan catalyzed by Bacillus subtilis levansucrase.
AB  - Under specific reaction conditions, levansucrase from Bacillus subtilis (SacB)
      catalyzes the synthesis of a low molecular weight levan through the non
      processive elongation of a great number of intermediates. To deepen understanding
      of the polymer elongation mechanism, we conducted a meticulous examination of the
      fructooligosaccharide profile evolution during the levan synthesis. As a result,
      the formation of primary and secondary intermediates series in different reaction
      stages was observed. The origin of the series was identified through comparison
      with product profiles obtained in acceptor reactions employing levanbiose,
      blastose, 1-kestose, 6-kestose, and neo-kestose, and supported with the isolation
      and NMR analyses of some relevant products, demonstrating that all of them are
      inherent products during levan formation from sucrose. These results allowed to
      establish the network of fructosyl transfer reactions involved in the non
      processive levan synthesis. Overall, our results reveal how the relaxed acceptor
      specificity of SacB during the initial steps of the synthesis is responsible for
      the formation of several levan series, which constitute the final low molecular
      weight levan distribution.

PMID- 30301901
TI  - A Pre-Clinical Large Animal Model of Sustained Liver Injury and Regeneration
      Stimulus.
AB  - A feasible large animal model to evaluate regenerative medicine techniques is
      vital for developing clinical applications. One such appropriate model could be
      to use retrorsine (RS) together with partial hepatectomy (PH). Here, we have
      developed the first porcine model using RS and PH. RS or saline control was
      administered intraperitoneally to Gottingen miniature pigs twice, two weeks
      apart. Four weeks after the second dose, animals underwent PH. Initially, we
      tested different doses of RS and resection of different amounts of liver, and
      selected 50 mg/kg RS with 60% hepatectomy as our model for further testing.
      Treated animals were sacrificed 3, 10, 17 or 28 days after PH. Blood samples and
      resected liver were collected. Serum and liver RS content was determined by
      Liquid Chromatograph-tandem Mass Spectrometer. Blood analyses demonstrated liver
      dysfunction after PH. Liver regeneration was significantly inhibited 10 and 17
      days after PH in RS-treated animals, to the extent of 20%. Histological
      examination indicated hepatic injury and regenerative responses after PH.
      Immunohistochemical staining demonstrated accumulation of Cyclin D1 and
      suppression of Ki-67 and PCNA in RS-treated animals. We report the development of
      the first large animal model of sustained liver injury with suppression of
      hepatic regeneration.

PMID- 30301902
TI  - Prevalence of the Metabolic Syndrome and its determinants among Nepalese adults:
      Findings from a nationally representative cross-sectional study.
AB  - Metabolic syndrome (MetS) increases the risk of cardiovascular diseases and
      diabetes mellitus. This study is designed to assess the prevalence and
      determinants of MetS among Nepalese adults from a nationally representative
      study. This study is based on Stepwise Approach to Surveillance (STEPS) Survey
      from Nepal. This survey was done among 4200 adults aged 15-69 years from 210
      clusters selected proportionately across Nepal's three ecological zones
      (Mountain, Hill and Terai). Subsequently, using systematic sampling, twenty
      households per cluster and one participant per household were selected. The
      overall prevalence of MetS is 15% and 16% according to Adult Treatment Panel III
      (ATP III) and International Diabetes Federation (IDF) criteria respectively. A
      triad of low HDL-C, abdominal obesity and high BP was the most prevalent (8.18%),
      followed by abdominal obesity, low HDL-C cholesterol and high triglycerides (8%).
      Less than two percent of participants had all the five components of the syndrome
      and 19% of participants had none. The prevalence steadily rose across the age
      group with adults aged 45-69 years having the highest prevalence (28-30%) and
      comparable prevalence across two definitions of MetS. A notably high burden for
      females, urban, hill or Terai resident were seen among other factors.

PMID- 30301903
TI  - Deletion of exon 4 in LAMA2 is the most frequent mutation in Chinese patients
      with laminin alpha2-related muscular dystrophy.
AB  - Although recessive mutations in LAMA2 are already known to cause laminin alpha2
      related muscular dystrophy, a rare neuromuscular disorder, large deletions or
      duplications within this gene are not well-characterized. In this study, we
      applied next-generation sequencing-based copy number variation profiling in 114
      individuals clinically diagnosed with laminin alpha2-related muscular dystrophy,
      including 96 who harboured LAMA2 mutations and 34 who harboured intragenic
      rearrangements. In total, we detected 18 distinct LAMA2 copy number variations
      that have been reported only among Chinese, 10 of which are novel. The frequency
      of CNVs in the cohort was 19.3%. Deletion of exon 4 was detected in 10 alleles of
      eight patients, accounting for 27% of all copy number variations. These patients
      are Han Chinese and were found to have the same haplotype and sequence at the
      breakpoint junction, suggesting that exon 4 deletion is a founder mutation in
      Chinese Han and a mutation hotspot. Moreover, the data highlight our approach, a
      modified next-generation sequencing assay, as a robust and sensitive tool to
      detect LAMA2 variants; the assay identifies 85.7% of breakpoint junctions
      directly alongside sequence information. The method can be applied to clinical
      samples to determine causal variants underlying various Mendelian disorders.

PMID- 30301904
TI  - Age-Related Measurements of the Myelin Water Fraction derived from 3D multi-echo
      GRASE reflect Myelin Content of the Cerebral White Matter.
AB  - Myelin Water Fraction (MWF) measurements derived from quantitative Myelin Water
      Imaging (MWI) may detect demyelinating changes of the cerebral white matter (WM)
      microstructure. Here, we investigated age-related alterations of the MWF in
      normal aging brains of healthy volunteers utilizing two fast and clinically
      feasible 3D gradient and spin echo (GRASE) MWI sequences with 3 mm and 5 mm
      isotropic voxel size. In 45 healthy subjects (age range: 18-79 years), distinct
      regions of interest (ROI) were defined in the cerebral WM including corticospinal
      tracts. For the 3 mm sequence, significant correlations of the mean MWF with age
      were found for most ROIs (r < -0.8 for WM ROIs; r = -0.55 for splenium of corpus
      callosum; r = -0.75 for genu of corpus callosum; p < 0.001 for all ROIs). Similar
      correlations with age were found for the ROIs of the 5 mm sequence. No
      significant correlations were found for the corticospinal tract and the occipital
      WM (p > 0.05). Mean MWF values obtained from the 3 mm and 5 mm sequences were
      strongly comparable. The applied 3D GRASE MWI sequences were found to be
      sensitive for age-dependent myelin changes of the cerebral WM microstructure. The
      reported MWF values might be of substantial use as reference for further
      investigations in patient studies.

PMID- 30301905
TI  - Higher species richness enhances yield stability in intensively managed
      grasslands with experimental disturbance.
AB  - Climate models predict increased frequency and severity of drought events. At an
      Irish and Swiss site, experimental summer droughts were applied over two
      successive years to grassland plots sown with one, two or four grassland species
      with contrasting functional traits. Mean yield and plot-to-plot variance of yield
      were measured across harvests during drought and after a subsequent post-drought
      recovery period. At both sites, there was a positive relationship between species
      richness and yield. Under rainfed control conditions, mean yields of four-species
      communities were 32% (Wexford, Ireland) and 51% (Zurich, Switzerland) higher than
      in monocultures. This positive relationship was also evident under drought,
      despite significant average yield reductions (-27% at Wexford; -21% at Zurich).
      Four-species communities had lower plot-to-plot variance of yield compared to
      monoculture or two-species communities under both rainfed and drought conditions,
      which demonstrates higher yield stability in four-species communities. At the
      Swiss but not the Irish site, a high degree of species asynchrony could be
      identified as a mechanism underlying increased temporal stability in four-species
      communities. These results indicate the high potential of multi-species
      grasslands as an adaptation strategy against drought events and help achieve
      sustainable intensification under both unperturbed and perturbed environmental
      conditions.

PMID- 30301906
TI  - Working Memory Training Improves Emotion Regulation Ability.
AB  - Emotion regulation deficits are associated with various emotional disorders.
      Therefore, studies have attempted to improve emotion regulation ability to
      prevent psychopathological symptoms. Studies have revealed that working memory
      training-specifically attention control-can promote emotion regulation. In the
      present study, participants completed a running memory task in a 20-day training
      period. The participants' pre- and post-test data on attention network functions
      and late positive potential (LPP) were assessed and analyzed. Compared with the
      control group, the training group's orientation function improved markedly. In
      addition, LPP in relation to emotion regulation decreased during the 20-day
      training period. These results suggest that working memory training can improve
      emotion regulation ability, and the orientation function in the attention network
      may also contribute to this improvement.

PMID- 30301907
TI  - CHI3L1 promotes tumor progression by activating TGF-beta signaling pathway in
      hepatocellular carcinoma.
AB  - CHI3L1 (YKL40) is a secreted glycoprotein and elevated serum CHI3L1 level has
      been proved to be associated with poor prognosis in many human cancers. However,
      the mechanism of how CHI3L1 causes poor prognosis in cancers is still unknown.
      Here, considering that CHI3L1 is a liver specific/enriched protein, we use
      hepatocellular carcinoma as a model to study the function of CHI3L1. We showed
      that, both in vivo and in vitro, overexpression of CHI3L1 could promote liver
      cancer cells growth, migration and invasion. We then used RNA-seq to analyze the
      expression profiles of CHI3L1 overexpressed in two HCC cell lines and found that
      CHI3L1 overexpression affected genes that were involved in cell-cell adhesion,
      extracellular exosome and adherens junction. Western blot analysis further
      revealed that CHI3L1 could activate TGF-beta signal pathways. Our data added new
      understanding of the mechanism of CHI3L1's action. 1) CHI3L1 promoted cancer cell
      proliferation by regulating cell cycles; 2) CHI3L1 promoted cancer cell invasion
      and metastasis; 3) CHI3L1 regulate liver cancer potentially by regulating the TGF
      beta signaling pathways; 4) CHI3L1 has direct kinase activities or activate
      kinase to phosphorylate SMAD2, SMAD3.

PMID- 30301908
TI  - Retraction Note: Hsa-miR-520d induces hepatoma cells to form normal liver tissues
      via a stemness-mediated process.
AB  - This paper has been retracted.

PMID- 30301909
TI  - Dual-controlled optogenetic system for the rapid down-regulation of protein
      levels in mammalian cells.
AB  - Optogenetic switches are emerging molecular tools for studying cellular processes
      as they offer higher spatiotemporal and quantitative precision than classical,
      chemical-based switches. Light-controllable gene expression systems designed to
      upregulate protein expression levels meanwhile show performances superior to
      their chemical-based counterparts. However, systems to reduce protein levels with
      similar efficiency are lagging behind. Here, we present a novel two-component,
      blue light-responsive optogenetic OFF switch ('Blue-OFF'), which enables a rapid
      and quantitative down-regulation of a protein upon illumination. Blue-OFF
      combines the first light responsive repressor KRAB-EL222 with the protein
      degradation module B-LID (blue light-inducible degradation domain) to
      simultaneously control gene expression and protein stability with a single
      wavelength. Blue-OFF thus outperforms current optogenetic systems for controlling
      protein levels. The system is described by a mathematical model which aids in the
      choice of experimental conditions such as light intensity and illumination regime
      to obtain the desired outcome. This approach represents an advancement of dual
      controlled optogenetic systems in which multiple photosensory modules operate
      synergistically. As exemplified here for the control of apoptosis in mammalian
      cell culture, the approach opens up novel perspectives in fundamental research
      and applications such as tissue engineering.

PMID- 30301910
TI  - A frequency reconfigurable dipole antenna with solid-state plasma in silicon.
AB  - A frequency reconfigurable dipole antenna based on a silicon radiator is
      presented. The silicon radiator is activated with the aid of highly dense solid
      state plasma by injecting carriers into the intrinsic region of p-i-n diodes. The
      fabrication and design guideline of the reconfigurable dipole antenna with this
      plasma radiator are described. When the plasma radiator is activated or
      deactivated, the length of the dipole arm changes, which means that the operating
      frequency of the dipole antenna is reconfigurable. When all the channels in the
      plasma radiator are activated, the operating frequency is tuned from 6.3 GHz to
      4.9 GHz. The measured tunable bandwidth of our fabricated dipole antenna is
      approximately 31%, which is a practical value in comparison to conventional
      frequency reconfigurable antennas whose tunable bandwidth is in a range from 20%
      to 50%. To further support the validity of our results, we provide the well
      matched simulation results from an antenna simulation. These results demonstrate
      that silicon with its commercial technology, which has not attracted attention in
      comparison to a metal antennas, is a promising tunable material for a frequency
      reconfigurable antenna. This plasma-based reconfigurable antenna has great
      potential for use in the dynamic communication environment.

PMID- 30301911
TI  - Selection of suitable reference genes for qRT-PCR normalisation under different
      experimental conditions in Eucommia ulmoides Oliv.
AB  - Normalisation of data, by choosing the appropriate reference genes, is
      fundamental for obtaining reliable results in quantitative real-time PCR (qPCR).
      This study evaluated the expression stability of 11 candidate reference genes
      with different varieties, developmental periods, tissues, and abiotic stresses by
      using four statistical algorithms: geNorm, NormFinder, BestKeeper, and RefFinder.
      The results indicated that ubiquitin-conjugating enzyme S (UBC) and ubiquitin
      conjugating enzyme E2 (UBC E2) could be used as reference genes for different E.
      ulmoides varieties and tissues, UBC and histone H4 (HIS4) for different
      developmental periods, beta-tubulin (TUB) and UBC for cold treatment, ubiquitin
      extension protein (UBA80) and HIS4 for drought treatment, and ubiquitin-60S
      ribosomal protein L40 (UBA52) and UBC E2 for salinity treatment. UBC and UBC E2
      for the group "Natural growth" and "Total", UBA80 and UBC for the group "Abiotic
      stresses". To validate the suitability of the selected reference genes in this
      study, mevalonate kinase (MK), phenylalanine ammonia-lyase (PAL), and 4-coumarate
      CoA ligase (4CL) gene expression patterns were analysed. When the most unstable
      reference genes were used for normalisation, the expression patterns had
      significant biases compared with the optimum reference gene combinations. These
      results will be beneficial for more accurate quantification of gene expression
      levels in E. ulmoides.

PMID- 30301912
TI  - Temperature-mediated invocation of the vacuum state for switchable ultrawide
      angle and broadband deflection.
AB  - Temperature-mediated appearance and disappearance of a deflection grating in a
      diffracting structure is possible by employing InSb as the grating material. InSb
      transits from the dielectric state to the plasmonic state in the terahertz regime
      as the temperature increases, this transition being reversible. An intermediate
      state is the vacuum state in which the real part of the relative permittivity of
      InSb equals unity while the imaginary part is much smaller. Then the grating
      virtually disappears, deflection being impossible as only specular reflection can
      occur. This ON/OFF switching of deflection and relevant angular filtering are
      realizable over wide ranges of frequency and incidence angle by a temperature
      change of as low as 20 K. The vacuum state of InSb invoked for ON/OFF switching
      of deflection and relevant angular filtering can also be obtained for thermally
      tunable materials other than InSb as well as by using non-thermal mechanisms.

PMID- 30301913
TI  - Positive effects of the catastrophic Hurricane Patricia on insect communities.
AB  - Highly seasonal conditions of tropical dry forests determine the temporal
      patterns of insect abundance. However, density-independent factors such as
      natural disturbances can abruptly change environmental conditions, affecting
      insect populations. We address the effects of the Hurricane Patricia (category 5)
      on species density and abundance of three feeding guilds of herbivorous insects
      (sap-sucking, folivorous beetles and xylophagous) and predatory beetles
      associated to the canopy of a tropical dry forest. Hurricane Patricia has been
      the strongest tropical hurricane ever reported in the Western Hemisphere.
      Herbivorous insects (sap-sucking and xylophagous) and predatory beetles increased
      in species density and abundance in the following months after the hurricane,
      compared to samples before it. The positive response of sap-sucking insects to
      Hurricane Patricia was probably related to an increase in the availability of new
      shoots and leaf meristems after the natural coppicing by the hurricane, while
      xylophagous guild seems to have been positively affected by the increase in the
      amount and diversity of deadwood resources. The positive response of predatory
      beetles may be the result of a bottom-up effect due to a greater availability of
      arthropod preys after the hurricane. We demonstrated that catastrophic hurricane
      disturbances could be important events that temporarily increase the species
      density and abundance of insects in tropical dry forests.

PMID- 30301914
TI  - Ultrafast polarization control by terahertz fields via pi-electron wavefunction
      changes in hydrogen-bonded molecular ferroelectrics.
AB  - Rapid polarization control by an electric field in ferroelectrics is important to
      realize high-frequency modulation of light, which has potential applications in
      optical communications. To achieve this, a key strategy is to use an electronic
      part of ferroelectric polarization. A hydrogen-bonded molecular ferroelectric,
      croconic acid, is a good candidate, since pi-electron polarization within each
      molecule is theoretically predicted to play a significant role in the
      ferroelectric-state formation, as well as the proton displacements. Here, we show
      that a sub-picosecond polarization modulation is possible in croconic acid using
      a terahertz pulse. The terahertz-pulse-pump second-harmonic-generation-probe and
      optical-reflectivity-probe spectroscopy reveal that the amplitude of polarization
      modulation reaches 10% via the electric-field-induced modifications of pi
      electron wavefunctions. Moreover, the measurement of electric-field-induced
      changes in the infrared molecular vibrational spectrum elucidates that the
      contribution of proton displacements to the polarization modulation is negligibly
      small. These results demonstrate the electronic nature of polarization in
      hydrogen-bonded molecular ferroelectrics. The ultrafast polarization control via
      pi-electron systems observed in croconic acid is expected to be possible in many
      other hydrogen-bonded molecular ferroelectrics and utilized for future high-speed
      optical-modulation devices.

PMID- 30301915
TI  - Functional analysis of polyketide synthase genes in the biocontrol fungus
      Clonostachys rosea.
AB  - Clonostachys rosea is a mycoparasitic fungus used for biological control of plant
      diseases. Its genome contains 31 genes putatively encoding for polyketide
      synthases (PKSs), 75% of which are arranged in biosynthetic gene clusters. Gene
      expression analysis during C. rosea interactions with the fungal plant pathogens
      Botrytis cinerea and Fusarium graminearum showed common and species-specific
      induction of PKS genes. Our data showed a culture media dependent correlation
      between PKS gene expression and degree of antagonism in C. rosea. The pks22 and
      pks29 genes were highly induced during fungal-fungal interactions but not during
      pigmentation, and gene deletion studies revealed that PKS29 was required for full
      antagonism against B. cinerea, and for biocontrol of fusarium foot rot on barley.
      Metabolite analysis revealed that Deltapks29 strains has a 50% reduced production
      (P = 0.001) of an unknown polyketide with molecular formula C15H28O3, while
      Deltapks22 strains lost the ability to produce four previously unknown
      polyketides named Clonorosein A-D. Clonorosein A and B were purified, their
      structures determined, and showed strong antifungal activity against B. cinerea
      and F. graminearum. These results show that PKS22 is required for production of
      antifungal polyketide Clonorosein A-D, and demonstrate the role of PKS29 in
      antagonism and biocontrol of fungal plant diseases.

PMID- 30301916
TI  - Toxoplasma gondii Manipulates Expression of Host Long Noncoding RNA during
      Intracellular Infection.
AB  - Long noncoding RNA (lncRNA) are non-protein-coding transcripts greater than 200
      nucleotides that regulate gene expression. The field of transcriptomics is only
      beginning to understand the role of lncRNA in host defense. Little is known about
      the role of lncRNA in the response to infection by intracellular pathogens such
      as Toxoplasma gondii. Using a microarray, we examined the differential expression
      of 35,923 lncRNAs and 24,881 mRNAs in mouse bone-marrow-derived macrophages
      during infection with high- and low-virulence T. gondii strains. We found that
      1,522 lncRNA molecules were differentially regulated during infection with the
      high-virulence Type I strain, versus 528 with the less-virulent Type II strain.
      Of these lncRNAs, 282 were co-regulated with a nearby or overlapping mRNA
      including approximately 60 mRNAs with immune-related functions. We validated the
      microarray for 4 lncRNAs and 4 mRNAs using qRT-PCR. Using deletion strains of T.
      gondii, we found that the secretory kinase ROP16 controls upregulation of lncRNAs
      Csf1-lnc and Socs2-lnc, demonstrating that the parasite directly manipulates host
      lncRNA expression. Given the number of regulated lncRNAs and the magnitude of the
      expression changes, we hypothesize that these molecules constitute both an
      additional regulatory layer in the host response to infection and a target for
      manipulation by T. gondii.

PMID- 30301918
TI  - Murine transcription factor Math6 is a regulator of placenta development.
AB  - The murine basic helix-loop-helix transcription (bHLH) factor mouse atonal
      homolog 6 (Math6) is expressed in numerous organs and supposed to be involved in
      several developmental processes. However, so far neither all aspects nor the
      molecular mechanisms of Math6 function have been explored exhaustively. To
      analyze the in vivo function of Math6 in detail, we generated a constitutive
      knockout (KO) mouse (Math6-/-) and performed an initial histological and
      molecular biological investigation of its main phenotype. Pregnant Math6-/-
      females suffer from a disturbed early placental development leading to the death
      of the majority of embryos independent of the embryonic Math6 genotype. A few
      placentas and fetuses survive the severe uterine hemorrhagic events at late mid
      gestation (E13.5) and subsequently develop regularly. However, these fetuses
      could not be born due to obstructions within the gravid uterus, which hinder the
      birth process. Characterization of the endogenous spatiotemporal Math6 expression
      during placenta development reveals that Math6 is essential for an ordered
      decidualization and an important regulator of the maternal-fetal endocrine
      crosstalk regulating endometrial trophoblast invasion and differentiation. The
      strongly disturbed vascularization observed in the maternal placenta appears as
      an additional consequence of the altered endocrine status and as the main cause
      for the general hemorrhagic crisis.

PMID- 30301917
TI  - An optogenetic toolbox of LOV-based photosensitizers for light-driven killing of
      bacteria.
AB  - Flavin-binding fluorescent proteins (FPs) are genetically encoded in vivo
      reporters, which are derived from microbial and plant LOV photoreceptors. In this
      study, we comparatively analyzed ROS formation and light-driven antimicrobial
      efficacy of eleven LOV-based FPs. In particular, we determined singlet oxygen
      (1O2) quantum yields and superoxide photosensitization activities via
      spectroscopic assays and performed cell toxicity experiments in E. coli. Besides
      miniSOG and SOPP, which have been engineered to generate 1O2, all of the other
      tested flavoproteins were able to produce singlet oxygen and/or hydrogen peroxide
      but exhibited remarkable differences in ROS selectivity and yield. Accordingly,
      most LOV-FPs are potent photosensitizers, which can be used for light-controlled
      killing of bacteria. Furthermore, the two variants Pp2FbFP and DsFbFP M49I,
      exhibiting preferential photosensitization of singlet oxygen or singlet oxygen
      and superoxide, respectively, were shown to be new tools for studying specific
      ROS-induced cell signaling processes. The tested LOV-FPs thus further expand the
      toolbox of optogenetic sensitizers usable for a broad spectrum of microbiological
      and biomedical applications.

PMID- 30301919
TI  - Promiscuous attraction of ligands within the ATP binding site of RyR2 promotes
      diverse gating behaviour.
AB  - ATP is an essential constitutive regulator of cardiac ryanodine receptors (RyR2),
      enabling small changes in cytosolic Ca2+ to trigger large changes in channel
      activity. With recent landmark determinations of the full structures of RyR1
      (skeletal isoform) and RyR2 using cryo-EM, and identification of the RyR1 ATP
      binding site, we have taken the opportunity to model the binding of fragments of
      ATP into RyR2 in order to investigate how the structure of the ATP site dictates
      the functional responses of ligands attracted there. RyR2 channel gating was
      assessed under voltage-clamp conditions and by [3H]ryanodine binding studies. We
      show that even the triphosphate (PPPi) moiety alone was capable of activating
      RyR2 but produced two distinct effects (activation or irreversible inactivation)
      that we suggest correspond to two preferred binding locations within the ATP
      site. Combinations of complementary fragments of ATP (Pi + ADP or PPi + AMP)
      could not reproduce the effects of ATP, however, the presence of adenosine
      prevented the inactivating PPPi effects, allowing activation similar to that of
      ATP. RyR2 appears to accommodate diverse types of molecules, including PPPi, deep
      within the ATP binding site. The most effective ligands, however, have at least
      three phosphate groups that are guided into place by a nucleoside.

PMID- 30301921
TI  - Comparison Of Four Dietary Scores As Determinants Of Coronary Heart Disease
      Mortality.
AB  - We aimed at comparing 2 a-priori -Mediterranean Adequacy Index (MAI), the Median
      Score (MED) - versus 2 a-posteriori, -Factor Analysis (FA2) and Principal
      Components analysis (PC2)- dietary scores in 1214 CHD-free men aged 45-64
      belonging to the Italian Rural Areas of the Seven Countries Study examined in
      1965 and followed-up for mortality during 40 years. CHD death was the end-point.
      Collection of dietary history allowed to define 17 main food groups expressed in
      gr/day and to compare dietary scores, each divided into 3 classes. Kaplan-Meier
      curves showed higher survival for classes 2 and 3 (healthy) versus class 1
      (unhealthy), but the log-rank test was not significant for the 2 a-priori scores.
      Cox proportional hazards models showed similar significant findings comparing
      class 3 with class 1 in the a-posteriori scores FA2 and PC2, with hazards ratios
      of 0.48 and 0.43, that became 0.65 and 0.53 respectively after adjusting for six
      specific risk factors for CHD (age, cigarette smoking, systolic blood pressure,
      serum cholesterol, body mass index and physical activity). Food intake of class 3
      in all 4 scores matched rather well the characteristics of the Mediterranean
      Diet. The poor performance of a-priori dietary scores was partly explained by the
      unexpected and direct relationship of fruit intake with CHD deaths. The
      superiority of a-posteriori dietary patterns could be in turn due to the
      specificity of the study population. External validations and comparisons of a
      priori versus a-posteriori dietary patterns in larger cohorts, using the same 17
      food groups explored here, are urgently needed.

PMID- 30301920
TI  - Overlapping motifs on the herpes viral proteins ICP27 and ORF57 mediate
      interactions with the mRNA export adaptors ALYREF and UIF.
AB  - The TREX complex mediates the passage of bulk cellular mRNA export to the nuclear
      export factor TAP/NXF1 via the export adaptors ALYREF or UIF, which appear to act
      in a redundant manner. TREX complex recruitment to nascent RNA is coupled with 5'
      capping, splicing and polyadenylation. Therefore to facilitate expression from
      their intronless genes, herpes viruses have evolved a mechanism to circumvent
      these cellular controls. Central to this process is a protein from the conserved
      ICP27 family, which binds viral transcripts and cellular TREX complex components
      including ALYREF. Here we have identified a novel interaction between HSV-1 ICP27
      and an N-terminal domain of UIF in vivo, and used NMR spectroscopy to locate the
      UIF binding site within an intrinsically disordered region of ICP27. We also
      characterized the interaction sites of the ICP27 homolog ORF57 from KSHV with UIF
      and ALYREF using NMR, revealing previously unidentified binding motifs. In both
      ORF57 and ICP27 the interaction sites for ALYREF and UIF partially overlap,
      suggestive of mutually exclusive binding. The data provide a map of the binding
      sites responsible for promoting herpes virus mRNA export, enabling future studies
      to accurately probe these interactions and reveal the functional consequences for
      UIF and ALYREF redundancy.

PMID- 30301922
TI  - Raman spectroscopic detection of high-grade cervical cytology: Using
      morphologically normal appearing cells.
AB  - This study aims to detect high grade squamous intraepithelial cells (HSIL) by
      investigating HSIL associated biochemical changes in morphologically normal
      appearing intermediate and superficial cells using Raman spectroscopy. Raman
      spectra (n = 755) were measured from intermediate and superficial cells from
      negative cytology ThinPrep specimens (n = 18) and from morphologically normal
      appearing intermediate and superficial cells from HSIL cytology ThinPrep
      specimens (n = 17). The Raman data was subjected to multivariate algorithms
      including the standard principal component analysis (PCA)-linear discriminant
      analysis (LDA) and partial least squares discriminant analysis (PLS-DA) together
      with random subsets cross-validation for discriminating negative cytology from
      HSIL. The PCA-LDA method yielded sensitivities of 74.9%, 72.8%, and 75.6% and
      specificities of 89.9%, 81.9%, and 84.5%, for HSIL diagnosis based on the dataset
      obtained from intermediate, superficial and mixed intermediate/superficial cells,
      respectively. The PLS-DA method provided improved sensitivities of 95.5%, 95.2%
      and 96.1% and specificities of 92.7%, 94.7% and 93.5% compared to the PCA-LDA
      method. The results demonstrate that the biochemical signatures of
      morphologically normal appearing cells can be used to discriminate between
      negative and HSIL cytology. In addition, it was found that mixed intermediate and
      superficial cells could be used for HSIL diagnosis as the biochemical differences
      between negative and HSIL cytology were greater than the biochemical differences
      between intermediate and superficial cell types.

PMID- 30301923
TI  - Genetic variations in TAS2R3 and TAS2R4 bitterness receptors modify papillary
      carcinoma risk and thyroid function in Korean females.
AB  - Type 2 taste receptors (T2Rs, TAS2Rs) mediate bitterness perception and are
      involved in diverse defence mechanisms in extraoral tissues. The thyrocyte
      expressed T2Rs control thyroid hormone production, and this regulatory role may
      be associated with susceptibility to thyroid diseases. This study examined
      whether the variations in TAS2Rs modify the risk of papillary thyroid carcinoma
      (PTC) and whether such T2R-related PTC risk is associated with genetically
      modified thyroid function. We conducted a case-control study with 763 Korean
      females, including 250 PTC cases. Seventy-three single-nucleotide polymorphisms
      in 13 TAS2R genes and the pre-diagnosis levels of 4 thyroid-related functional
      markers [total triiodothyronine (TT3), free thyroxine, thyroid-stimulating
      hormone and thyroglobulin] were analysed. Individuals with TAS2R3/4 CC haplotype
      (rs2270009 and rs2234001) were at a lower risk for PTC than those with the
      remaining haplotypes (odds ratio = 0.59, 95% confidence interval: 0.36-0.97).
      Furthermore, TT3 levels were significantly reduced for TAS2R3/4 CC haplotype
      carriers compared with other haplotype carriers (p = 0.005). No other genetic
      variants exhibited critical associations with the PTC phenotype and biomarkers.
      In summary, genetic variations in T2R3/4 bitterness receptors may modify the PTC
      risk, and the genetically modified thyroid hormone level by those variations may
      be linked with the PTC-T2Rs association.

PMID- 30301925
TI  - Multiplex Biomarker Screening Assay for Urinary Extracellular Vesicles Study: A
      Targeted Label-Free Proteomic Approach.
AB  - The recent advance in targeted label-free proteomics, SWATH-MS, can provide
      consistent protein detection and reproducible protein quantitation, which is a
      considerable advantage for biomarker study of urinary extracellular vesicles. We
      developed a SWATH-MS workflow with a curated spectral library of 1,145 targets.
      Application of the workflow across nine replicates of three sample types (exosome
      like vesicles (ELVs), microvesicles (MVs) and urine proteins (UPs)) resulted in
      the quantitation of 888 proteins at FDR <1%. The median-coefficient of variation
      of the 888 proteins in the ELV sample was 7.7%, indicating excellent
      reproducibility. Data analysis showed common exosome markers, (i.e. CD9, CD63,
      ALIX, TSG101 and HSP70) were enriched in urinary ELVs as compared to MVs and UPs.
      The use of a multiplex biomarker screening assay focused on ELVs was
      investigated, and perspectives in future applications are discussed.

PMID- 30301924
TI  - Viable Mice with Extensive Gene Humanization (25-kbp) Created Using Embryonic
      Stem Cell/Blastocyst and CRISPR/Zygote Injection Approaches.
AB  - Here, we describe an expansion of the typical DNA size limitations associated
      with CRISPR knock-in technology, more specifically, the physical extent to which
      mouse genomic DNA can be replaced with donor (in this case, human) DNA at an
      orthologous locus by zygotic injection. Driving our efforts was the desire to
      create a whole animal model that would replace 17 kilobase pairs (kbp) of the
      mouse Bcl2l11 gene with the corresponding 25-kbp segment of human BCL2L11,
      including a conditionally removable segment (2.9-kbp) of intron 2, a cryptic
      human exon immediately 3' of this, and a native human exon some 20 kbp
      downstream. Using two methods, we first carried out the replacement by employing
      a combination of bacterial artificial chromosome recombineering, classic
      embryonic stem cell (ESC) targeting, dual selection, and recombinase-driven
      cassette removal (ESC/Blastocyst Approach). Using a unique second method, we
      employed the same vector (devoid of its selectable marker cassettes),
      microinjecting it along with redundant single guide RNAs (sgRNAs) and Cas9 mRNA
      into mouse zygotes (CRISPR/Zygote Approach). In both instances, we were able to
      achieve humanization of Bcl2l11 to the extent designed, remove all selection
      cassettes, and demonstrate the functionality of the conditionally removable, loxP
      flanked, 2.9-kbp intronic segment.

PMID- 30301926
TI  - Effects of coumaphos and imidacloprid on honey bee (Hymenoptera: Apidae) lifespan
      and antioxidant gene regulations in laboratory experiments.
AB  - The main objective of this study was to test comparatively the effects of two
      common insecticides on honey bee Apis mellifera worker's lifespan, food
      consumption, mortality, and expression of antioxidant genes. Newly emerged worker
      bees were exposed to organophosphate insecticide coumaphos, a neonicotinoid
      imidacloprid, and their mixtures. Toxicity tests were conducted along with bee
      midgut immunohistological TUNEL analyses. RT-qPCR assessed the regulation of 10
      bee antioxidant genes linked to pesticide toxicity. We tested coumaphos at 92,600
      ppb concentration, in combination with 5 and 20 ppb imidacloprid. Coumaphos
      induced significantly higher bee mortality, which was associated with down
      regulation of catalase compared to coumaphos and imidacloprid (5/20 ppb)
      mixtures, whereas, both imidacloprid concentrations independently had no effect
      on bee mortality. Mixture of coumaphos and imidacloprid reduced daily bee
      consumption of a control food patty to 10 mg from a coumaphos intake of 14.3 mg
      and 18.4 and 13.7 mg for imidacloprid (5 and 20) ppb, respectively. While
      coumaphos and imidacloprid mixtures induced down-regulation of antioxidant genes
      with noticeable midgut tissue damage, imidacloprid induced intensive gene up
      regulations with less midgut apoptosis.

PMID- 30301927
TI  - Losses of natural coastal wetlands by land conversion and ecological degradation
      in the urbanizing Chinese coast.
AB  - Coastal wetland ecosystems have experienced serious losses of area and ecological
      function and are currently facing worldwide challenges due to coastal development
      and global climate change. This study attempted to explore patterns and possible
      factors driving loss of natural coastal wetlands due to land conversion
      (permanent loss) and ecological degradation (temporal loss) in three urbanizing
      coastal city clusters, China in the period of 1990-2015. The natural coastal
      wetland area was substantially lost due to land conversion highly related to
      regional economic development. The ecological degradation, assessed as a function
      of surface water quality, resulted in much greater impairment area of natural
      coastal wetlands. This impairment was predominantly driven by inbound river
      pollutants' discharge, rather than local discharge. This study suggests that the
      ecological degradation should be considered as well as the land conversion loss
      for conserving the remaining natural coastal wetland ecosystems. The pollutant
      discharges from the inbound river watersheds need to be mitigated as the local
      discharges for reducing the functional degradation of the natural coastal
      wetlands while the regional economic development plan should consider the
      conservation needs of the remaining natural coastal wetlands worldwide.

PMID- 30301928
TI  - Effect of the Ratio of Magnetite Particle Size to Microwave Penetration Depth on
      Reduction Reaction Behaviour by H2.
AB  - In this study, we investigated reduction of magnetite by H2 during microwave
      irradiation. This process combines the advantages of microwave irradiation and
      using H2 as a reducing agent to mitigate CO2 emissions during the ironmaking
      process. Weight change measurements showed that a reduction of 75% was achieved
      after treatment under H2 for 60 min. For better understanding of the effective
      parameters in microwave chemistry, scanning electron microscopy, combined with
      energy-dispersive X-ray spectroscopy (SEM-EDX), was performed, which demonstrated
      a greater reduction of large particles (>40 MUm) than small particles. This
      behaviour could be attributed to the higher microwave absorption capability of
      large particles with a higher ratio of particle size to penetration depth
      (d/delta). Small particles behave as transparent material and are heated via
      conduction and/or convection; thus, there is no contribution from the catalytic
      effect of microwaves to the reduction reaction. Moreover, the reduction of Fe3O4
      to Fe0.94O, followed by transformation to Fe, seems to proceed from the surface
      toward the centre of the particle despite the volumetric microwave heating. This
      could be due to the higher gas accessibility of iron oxide on the particle
      surface than in the particle centre.

PMID- 30301929
TI  - Information transfer in QT-RR dynamics: Application to QT-correction.
AB  - The relation between the electrical properties of the heart and the beating rate
      is essential for the heart functioning. This relation is central when calculating
      the "corrected QT interval" - an important measure of the risk of potentially
      lethal arrhythmias. We use the transfer entropy method from information theory to
      quantitatively study the mutual dynamics of the ventricular action potential
      duration (the QT interval) and the length of the beat-to-beat (RR) interval. We
      show that for healthy individuals there is a strong asymmetry in the information
      transfer: the information flow from RR to QT dominates over the opposite flow
      (from QT to RR), i.e. QT depends on RR to a larger extent than RR on QT.
      Moreover, the history of the intervals has a strong effect on the information
      transfer: at sufficiently long QT history length the information flow asymmetry
      inverts and the RR influence on QT dynamics weakens. Finally, we demonstrate that
      the widely used QT correction methods cannot properly capture the changes in the
      information flows between QT and RR. We conclude that our results obtained
      through a model-free informational perspective can be utilised to improve and
      test the QT correction schemes in clinics.

PMID- 30301931
TI  - BETting on YAP-TAZ.

PMID- 30301932
TI  - Neighbourly deaths dictate fate.

PMID- 30301930
TI  - Apelin inhibited epithelial-mesenchymal transition of podocytes in diabetic mice
      through downregulating immunoproteasome subunits beta5i.
AB  - The epithelial-mesenchymal transition (EMT) of podocytes had been reported to be
      involved in the glomerular fibrosis in diabetic kidney diseases, which was
      regulated by TGFbeta and NFkappaB pathways. And apelin, an adipokine which is
      upregulated in diabetic kidney diseases, was reported to be negatively correlated
      to TGFbeta in polycystic kidney disease and attenuate EMT in renal tubular cells.
      Therefore, it is hypothesized that apelin might inhibit the EMT of podocytes
      through downregulating the expression and activation of TGFbeta/Smad pathway in
      diabetic kidney diseases. The results showed that apelin in glomeruli of diabetic
      mice were increased and exogenous apelin inhibited the EMT of podocytes in
      diabetic mice, which were accompanied with the decreased expression of proteasome
      subunits beta5i. The results from beta5iKO mice confirmed that the inhibiting
      effects of apelin on EMT of podocytes in diabetic mice were dependent on beta5i.
      The results from culture podocytes showed that apelin decreased the degradation
      of pIkappaB and promoted the translocation of IkappaB into nucleus through
      decreasing the expression of beta5i, which would inhibit the promoting effects of
      NFkappaB on expression of TGFbeta and followed by decreased activation of Smad
      pathway and EMT in podocytes. In conclusion, apelin might act as an EMT
      suppressor for podocytes to decrease the process of glomerular fibrosis in
      diabetic mice.

PMID- 30301934
TI  - Tumor DNA-dependent protein kinase catalytic subunit expression is associated
      with hepatitis B surface antigen status and tumor progression in patients with
      hepatocellular carcinoma.
AB  - The DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which plays an
      important role in the DNA damage response, has been reported to be associated
      with tumor progression in various carcinomas. However, the clinical significance
      of DNA-PKcs in hepatocellular carcinoma (HCC) patients remains unclear. In the
      present study, we determined the tumor expression of DNA-PKcs in 104 resected HCC
      specimens by immunohistochemistry. The DNA-PKcs expression was scored as follows;
      0, negative staining; 1, staining of nuclei at the tumor edge; 2, staining of the
      nuclei deep within the tumor and/or the tumor cytoplasm. The relationships
      between tumor expression of DNA-PKcs and the clinical characteristics and patient
      outcomes were investigated. Among the 104 HCCs, the distribution of staining for
      DNA-PKcs was as follows: 32 tumors were assigned a score of 0, 27 tumors were
      assigned a score of 1, and 45 tumors were assigned a score of 2. Statistical
      analyses revealed that tumor DNA-PKcs expression was significantly associated
      with the HBs antigen (HBsAg) status, presence/absence of portal vein invasion,
      size of the largest tumor nodule (<3.0 cm/>3.0, cm), and the serum alpha
      fetoprotein level. Significant differences in the overall survival and recurrence
      free survival were observed between patients showing (staining score 1 or 2) and
      not showing (staining score 0) tumor DNA-PKcs expression (P = 0.049 and P =
      0.045, respectively). Our results suggest that tumor expression of DNA-PKcs is
      associated with tumor progression, HBsAg status and the postoperative outcomes in
      patients with HCC.

PMID- 30301935
TI  - Naturally Occurring Variations Modulate the Activity of the HPV33 Early Promoter
      and its Affinity for the E2 Transcription Factor.
AB  - The human papillomavirus (HPV) Long Control Region (LCR) encompasses the early
      promoter (EP) that drives transcription of the E6 and E7 oncogenes in
      keratinocytes and HPV-associated cancers. In this study, the transcriptional
      activities of the HPV33 EP from the prototype LCR and from eight variants
      representative of the worldwide diversity of the virus were examined in primary
      human keratinocytes (PHK) and in the HeLa cervical carcinoma cell line by
      luciferase reporter-gene assays. Remarkably, the two variations with the greatest
      effect on the EP in PHK were C7732G and a 79-bp deletion that were associated
      with high-grade cervical lesions and persistent infections, respectively, in
      epidemiological studies. In contrast, the three variations most active in HeLa
      cells were C7537A, A7874C and A7879G. A7874C, which lies within an E2-binding
      sequence, is also shown to increase the activity and binding of E2 at this site.
      Collectively, these results indicate that naturally-occurring variations affect
      the HPV33 EP differentially in PHK than in cancer cells and, furthermore, that
      they can also alter its regulation by E2. These findings provide a molecular
      basis for rationalizing the results of previous epidemiological studies and for
      understanding the contribution of LCR polymorphisms to the oncogenicity and
      persistence of HPV33 infections.

PMID- 30301933
TI  - Development of a Molecular Adjuvant to Enhance Antigen-Specific CD8+ T Cell
      Responses.
AB  - Despite promising progress in malaria vaccine development, an efficacious subunit
      vaccine against P. falciparum remains to be licensed and deployed. This study
      aimed to improve on the immunogenicity of the leading liver-stage vaccine
      candidate (ChAd63-MVA ME-TRAP), known to confer protection by eliciting high
      levels of antigen-specific CD8+ T cells. We previously showed fusion of ME-TRAP
      to the human MHC class II invariant chain (Ii) could enhance CD8+ T cell
      responses in non-human primates, but did not progress to clinical testing due to
      potential risk of auto-immunity by vaccination of humans with a self-antigen.
      Initial immunogenicity analyses of ME-TRAP fused to subdomains of the Ii showed
      that the Ii transmembrane domain alone can enhance CD8+ T cell responses.
      Subsequently, truncated Ii sequences with low homology to human Ii were developed
      and shown to enhance CD8+ T cell responses. By systematically mutating the TM
      domain sequence, multimerization of the Ii chain was shown to be important for
      immune enhancement. We subsequently identified several proteins from a variety of
      microbial pathogens with similar characteristics, that also enhance the CD8+ T
      cell response and could therefore be used in viral vector vaccines when potent
      cell mediated immunity is required.

PMID- 30301936
TI  - Losing half the conductive area hardly impacts the water status of mature trees.
AB  - The water status of transpiring tree crowns depends on a hydraulic continuum from
      the soil matrix around roots to the sub-stomatal cavity of leaves, with a
      multitude of hydraulic resistances along this path. Although the stem xylem path
      may not be the most critical of these resistances, it had been suggested that a
      >50% interruption of that path by drought-stress-induced embolization (air
      filling) of conduits is critical for tree survival. Here we show that cutting the
      sapwood of mature, 35 m tall trees in half hardly affects crown water status and
      transpiration. Counter expectation, this first adult tree sapwood interception
      experiment revealed that shoot water potential in the canopy (assessed by using a
      45 m canopy crane) either remained unaffected (spruce) or became less negative
      (beech), associated with small reductions in leaf diffusive conductance for water
      vapour. We conclude that the stem xylem of these trees has a large overcapacity
      and the tree hydraulics debate requires a critical re-visitation.

PMID- 30301937
TI  - How to be NICEr in treating osteoarthritis.

PMID- 30301938
TI  - The microbiome and HLA-B27-associated acute anterior uveitis.
AB  - Acute anterior uveitis (AAU) and the spondyloarthritis (SpA) subtypes ankylosing
      spondylitis, reactive arthritis and psoriatic arthritis are among the
      inflammatory diseases affected by the biology of the intestinal microbiome. In
      this Review, the relationship between AAU, SpA and the microbiome is discussed,
      with a focus on the major SpA risk gene HLA-B*27 and how it is associated with
      both intestinal tolerance and the loss of ocular immune privilege that can
      accompany AAU. We provide four potential mechanisms to account for how dysbiosis,
      barrier function and immune response contribute to the development of ocular
      inflammation and the pathogenesis of AAU. Finally, potential therapeutic avenues
      to target the microbiota for the clinical management of AAU and SpA are outlined.

PMID- 30301940
TI  - Early developmental assessment with a short screening test, the STEP, predicts
      one-year outcomes.
AB  - OBJECTIVE: To evaluate the Specific Test of Early Infant Motor Performance
      (STEP), a rapid screening test of preterm infants at risk for developmental
      delay. STUDY DESIGN: We prospectively studied 23 preterm infants' performance on
      the STEP and the Test of Infant Motor Performance (TIMP) at term and 3 months,
      and on the Bayley-III at 12 months. We investigated the psychometric qualities of
      the STEP and determined STEP cutoff scores for low and high-performing infants.
      RESULTS: STEP scores at term and 3 months strongly correlate with 12-month Bayley
      III gross motor and cognitive scaled scores, while TIMP scores did not. The STEP
      showed excellent reliability and required 6-10 min to administer. CONCLUSION:
      STEP is a short, easy to administer, early developmental assessment with unique
      scoring that emphasizes qualitative and quantitative aspects of muscle tone in
      movements and predicts 12-month Bayley gross motor and cognitive scaled scores.

PMID- 30301939
TI  - LEM4 confers tamoxifen resistance to breast cancer cells by activating cyclin D
      CDK4/6-Rb and ERalpha pathway.
AB  - The elucidation of molecular events that confer tamoxifen resistance to estrogen
      receptor alpha (ER) positive breast cancer is of major scientific and therapeutic
      importance. Here, we report that LEM4 overexpression renders ER+ breast cancer
      cells resistant to tamoxifen by activating the cyclin D-CDK4/6 axis and the
      ERalpha signaling. We show that LEM4 overexpression accelerates tumor growth.
      Interaction with LEM4 stabilizes CDK4 and Rb, promotes Rb phosphorylation and the
      G1/S phase transition. LEM4 depletion or combined tamoxifen and PD0332991
      treatment significantly reverses tamoxifen resistance. Furthermore, LEM4
      interacts with and stabilizes both Aurora-A and ERalpha, promotes Aurora-A
      mediated phosphorylation of ERalpha-Ser167, leading to increase in ERalpha DNA
      binding and transactivation activity. Elevated levels of LEM4 correlates with
      poorer relapse-free survival in patients with ER+ breast cancer undergoing
      endocrine therapy. Thus, LEM4 represents a prognostic marker and an attractive
      target for breast cancer therapeutics. Functional antagonism of LEM4 could
      overcome tamoxifen resistance.

PMID- 30301941
TI  - Publisher Correction: Tau folds differently between diseases.
AB  - In the original version of this article published online, Michel Goedert's first
      name was spelt incorrectly and the affiliation of Sjors Scheres was incorrect.
      These errors have been corrected in the HTML and PDF versions of the article.

PMID- 30301942
TI  - Simultaneous evaluation of anti-EGFR-induced tumour and adverse skin effects in a
      microfluidic human 3D co-culture model.
AB  - Antibody therapies targeting the epithelial growth factor receptor (EGFR) are
      being increasingly applied in cancer therapy. However, increased tumour
      containment correlates proportionally with the severity of well-known adverse
      events in skin. The prediction of the latter is not currently possible in
      conventional in vitro systems and limited in existing laboratory animal models.
      Here we established a repeated dose "safficacy" test assay for the simultaneous
      generation of safety and efficacy data. Therefore, a commercially available multi
      organ chip platform connecting two organ culture compartments was adapted for the
      microfluidic co-culture of human H292 lung cancer microtissues and human full
      thickness skin equivalents. Repeated dose treatment of the anti-EGFR-antibody
      cetuximab showed an increased pro-apoptotic related gene expression in the tumour
      microtissues. Simultaneously, proliferative keratinocytes in the basal layer of
      the skin microtissues were eliminated, demonstrating crucial inhibitory effects
      on the physiological skin cell turnover. Furthermore, antibody exposure modulated
      the release of CXCL8 and CXCL10, reflecting the pattern changes seen in antibody
      treated patients. The combination of a metastatic tumour environment with a
      miniaturized healthy organotypic human skin equivalent make this "safficacy"
      assay an ideal tool for evaluation of the therapeutic index of EGFR inhibitors
      and other promising oncology candidates.

PMID- 30301943
TI  - Intranasal delivery of a Fas-blocking peptide attenuates Fas-mediated apoptosis
      in brain ischemia.
AB  - Ischemic stroke-induced neuronal cell death results in the permanent disabling of
      brain function. Apoptotic mechanisms are thought to play a prominent role in
      neuronal injury and ample evidence implicates Fas signaling in mediating cell
      death. In this study, we describe the neuroprotective effects of a Fas-blocking
      peptide (FBP) that by obstructing Fas signaling in cerebral ischemia inhibits
      apoptosis. Using an intranasal administration route in a rat model of focal
      cerebral ischemia, we demonstrate that nose-to-brain delivery of FBP after middle
      cerebral artery occlusion (MCAO) surgery results in the delivery and retention of
      FBP in Fas-expressing ischemic areas of the brain. A single intranasal
      administration of 2 mg/kg FBP resulted in significantly reduced neuronal cell
      death by inhibiting Fas-mediated apoptosis leading to decreased infarct volumes,
      reduced neurologic deficit scores and recovery from cerebral ischemia.
      Intranasally delivered FBP might be a promising strategy for the treatment of
      cerebral ischemic stroke.

PMID- 30301944
TI  - Heritability of cerebral glutamate levels and their association with
      schizophrenia spectrum disorders: a 1[H]-spectroscopy twin study.
AB  - Research findings implicate cerebral glutamate in the pathophysiology of
      schizophrenia, including genetic studies reporting associations with
      glutamatergic neurotransmission. The extent to which aberrant glutamate levels
      can be explained by genetic factors is unknown, and if glutamate can serve as a
      marker of genetic susceptibility for schizophrenia remains to be established. We
      investigated the heritability of cerebral glutamate levels and whether a
      potential association with schizophrenia spectrum disorders could be explained by
      genetic factors. Twenty-three monozygotic (MZ) and 20 dizygotic (DZ) proband
      pairs con- or discordant for schizophrenia spectrum disorders, along with healthy
      control pairs (MZ = 28, DZ = 18) were recruited via the National Danish Twin
      Register and the Psychiatric Central Register (17 additional twins were scanned
      without their siblings). Glutamate levels in the left thalamus and the anterior
      cingulate cortex (ACC) were measured using 1[H]-magnetic resonance spectroscopy
      at 3 Tesla and analyzed by structural equation modeling. Glutamate levels in the
      left thalamus were heritable and positively correlated with liability for
      schizophrenia spectrum disorders (phenotypic correlation, 0.16, [0.02-0.29]; p =
      0.010). The correlation was explained by common genes influencing both the levels
      of glutamate and liability for schizophrenia spectrum disorders. In the ACC,
      glutamate and glx levels were heritable, but not correlated to disease liability.
      Increases in thalamic glutamate levels found in schizophrenia spectrum disorders
      are explained by genetic influences related to the disease, and as such the
      measure could be a potential marker of genetic susceptibility, useful in early
      detection and stratification of patients with psychosis.

PMID- 30301945
TI  - Decision-making of the benthic diatom Seminavis robusta searching for inorganic
      nutrients and pheromones.
AB  - Microorganisms encounter a diversity of chemical stimuli that trigger individual
      responses and influence population dynamics. However, microbial behavior under
      the influence of different incentives and microbial decision-making is poorly
      understood. Benthic marine diatoms that react to sexual attractants as well as to
      nutrient gradients face such multiple constraints. Here, we document and model
      behavioral complexity and context-sensitive responses of these motile unicellular
      algae to sex pheromones and the nutrient silicate. Throughout the life cycle of
      the model diatom Seminavis robusta nutrient-starved cells localize sources of
      silicate by combined chemokinetic and chemotactic motility. However, with an
      increasing need for sex to restore the initial cell size, a change in behavior
      favoring the attraction-pheromone-guided search for a mating partner takes place.
      When sex becomes inevitable to prevent cell death, safeguard mechanisms are
      abandoned, and cells prioritize the search for mating partners. Such selection
      processes help to explain biofilm organization and to understand species
      interactions in complex communities.

PMID- 30301946
TI  - Induction of antibacterial proteins and peptides in the coprophilous mushroom
      Coprinopsis cinerea in response to bacteria.
AB  - Bacteria are the main nutritional competitors of saprophytic fungi during
      colonization of their ecological niches. This competition involves the mutual
      secretion of antimicrobials that kill or inhibit the growth of the competitor.
      Over the last years it has been demonstrated that fungi respond to the presence
      of bacteria with changes of their transcriptome, but the significance of these
      changes with respect to competition for nutrients is not clear as functional
      proof of the antibacterial activity of the induced gene products is often
      lacking. Here, we report the genome-wide transcriptional response of the
      coprophilous mushroom Coprinopsis cinerea to the bacteria Bacillus subtilis and
      Escherichia coli. The genes induced upon co-cultivation with each bacterium were
      highly overlapping, suggesting that the fungus uses a similar arsenal of
      effectors against Gram-positive and -negative bacteria. Intriguingly, the induced
      genes appeare to encode predominantly secreted peptides and proteins with
      predicted antibacterial activities, which was validated by comparative proteomics
      of the C. cinerea secretome. Induced members of two putative antibacterial
      peptide and protein families in C. cinerea, the cysteine-stabilized alphabeta
      defensins (Csalphabeta-defensins) and the GH24-type lysozymes, were purified, and
      their antibacterial activity was confirmed. These results provide compelling
      evidence that fungi are able to recognize the presence of bacteria and respond
      with the expression of an arsenal of secreted antibacterial peptides and
      proteins.

PMID- 30301947
TI  - Stress-induced changes in social dominance are scaled by AMPA-type glutamate
      receptor phosphorylation in the medial prefrontal cortex.
AB  - The establishment and maintenance of social dominance are critical for social
      stability and the survival and health of individual animals. Stress lead to
      depression and a decrease in the social status of depressed persons is a risk
      factor for suicide. Therefore, we explored the mechanistic and behavioral links
      among stress, depression, and social dominance and found that mice subjected to
      chronic restraint stress (CRS), an animal model of stress-induced depression,
      showed decreased social dominance as measured by a dominance tube test.
      Importantly, this submissive behavior was occluded by the antidepressant,
      fluoxetine, a selective serotonin reuptake inhibitor. It is known that social
      dominance is controlled by synaptic efficacy in the medial prefrontal cortex
      (mPFC) and that AMPA-type glutamate receptor (AMPA-R) is a key molecule for
      synaptic efficacy. We found that the phosphorylation on AMPA-R was
      bidirectionally changed by CRS and fluoxetine in the mPFC of mice with CRS.
      Moreover, we found a strong correlation between social dominance and AMPA-R
      phosphorylation that regulates synaptic efficacy by modulating the synaptic
      targeting of AMPA-R. Our correlational analysis of the behavior and biochemistry
      of the CRS model suggests that AMPA-R phosphorylation in the mPFC may serve as a
      biomarker of social dominance related to stress.

PMID- 30301948
TI  - Towards epitaxial graphene p-n junctions as electrically programmable quantum
      resistance standards.
AB  - We report the fabrication and measurement of top gated epitaxial graphene p-n
      junctions where exfoliated hexagonal boron nitride (h-BN) is used as the gate
      dielectric. The four-terminal longitudinal resistance across a single junction is
      well quantized at the von Klitzing constant [Formula: see text] with a relative
      uncertainty of 10-7. After the exploration of numerous parameter spaces, we
      summarize the conditions upon which these devices could function as potential
      resistance standards. Furthermore, we offer designs of programmable electrical
      resistance standards over six orders of magnitude by using external gating.

PMID- 30301949
TI  - Microclimate exerts greater control over litter decomposition and enzyme activity
      than litter quality in an alpine forest-tundra ecotone.
AB  - Plant litter decomposition is an important biogeochemical process in terrestrial
      ecosystems. Although climate and substrate quality controls over litter
      decomposition are reasonably well understood, their impacts on lignocellulose
      degradation and lignocellulolytic enzymes remain elusive. Here, the decomposition
      of three leaf litters derived from Salix paraplesia (SP), Deyeuxia scabrescens
      (DS), and Ajuga ovalifolia (AO), was studied across an alpine forest-tundra
      ecotone during one snow-covered season with the objective of distinguishing
      between the effects of microclimate and litter quality on litter decomposition
      rates and lignocellulolytic enzymes. The results showed that both microclimate
      and litter quality affected lignocellulose degradation rates and
      lignocellulolytic enzyme activities; however, microclimate factors had the
      greater effects. Interestingly, freeze-thaw cycles and moisture were the
      predominant factors explaining the variations in decomposition rate and enzyme
      activities. Higher cellulose degradation rates were associated with higher
      cellulose concentrations. Cellulolytic enzymes had a greater effect on litter
      decomposition than did ligninolytic enzymes at the early decomposition stage.
      Litter decomposition and enzyme activities should be given more attention under
      global climate change, as the direction and magnitude of changes in microclimate
      factors and litter quality could strongly influence the nutrient cycling and
      energy fluxes of alpine ecosystems.

PMID- 30301950
TI  - Tree shrew as a new animal model to study the pathogenesis of avian influenza
      (H9N2) virus infection.
AB  - Outbreaks of avian influenza virus continue to pose threats to human health.
      Animal models such as the mouse, ferret, and macaque are used to understand the
      pathogenesis of avian influenza virus infection in humans. We previously reported
      that the tree shrew (Tupaia belangeri, family Tupaiidae), which is regarded as a
      "low-level primate", has alpha2,3- and alpha2,6-linked sialic acid receptor
      distributions similar to those of humans and is potentially a useful mammalian
      model for studying mild human influenza (H1N1) virus infection. In this study, we
      used the tree shrew experimental model to investigate the pathogenesis of avian
      influenza A (H9N2) virus infection and the effect of the E627K mutation in the
      PB2 gene, an adaptation to mammalian hosts. Evidence of disease, virus titers in
      the upper and lower respiratory tract, histopathology and induction of
      proinflammatory cytokines are described. We also established ex vivo culture
      models of tree shrew respiratory tissues to study the tropism and replication of
      the H9N2 virus. Our results demonstrated that the tree shrew is a viable new in
      vivo experimental model for avian influenza research that provides results
      comparable to those observed in ferrets. The disease spectrum and pathogenesis in
      tree shrews correlate well with what is observed in humans.

PMID- 30301952
TI  - A position on vision.

PMID- 30301951
TI  - Circadian monitoring as an aging predictor.
AB  - The ageing process is associated with sleep and circadian rhythm (SCR) frailty,
      as well as greater sensitivity to chronodisruption. This is essentially due to
      reduced day/night contrast, decreased sensitivity to light, napping and a more
      sedentary lifestyle. Thus, the aim of this study is to develop an algorithm to
      identify a SCR phenotype as belonging to young or aged subjects. To do this, 44
      young and 44 aged subjects were recruited, and their distal skin temperature
      (DST), activity, body position, light, environmental temperature and the
      integrated variable TAP rhythms were recorded under free-living conditions for
      five consecutive workdays. Each variable yielded an individual decision tree to
      differentiate between young and elderly subjects (DST, activity, position, light,
      environmental temperature and TAP), with agreement rates of between 76.1% (light)
      and 92% (TAP). These decision trees were combined into a unique decision tree
      that reached an agreement rate of 95.3% (4 errors out of 88, all of them around
      the cut-off point). Age-related SCR changes were very significant, thus allowing
      to discriminate accurately between young and aged people when implemented in
      decision trees. This is useful to identify chronodisrupted populations that could
      benefit from chronoenhancement strategies.

PMID- 30301954
TI  - Correction to: TRIM50 suppressed hepatocarcinoma progression through directly
      targeting SNAIL for ubiquitous degradation.

PMID- 30301953
TI  - The neural mechanisms and circuitry of the pair bond.
AB  - Love is one of our most powerful emotions, inspiring some of the greatest art,
      literature and conquests of human history. Although aspects of love are surely
      unique to our species, human romantic relationships are displays of a mating
      system characterized by pair bonding, likely built on ancient foundational neural
      mechanisms governing individual recognition, social reward, territorial behaviour
      and maternal nurturing. Studies in monogamous prairie voles and mice have
      revealed precise neural mechanisms regulating processes essential for the pair
      bond. Here, we discuss current viewpoints on the biology underlying pair bond
      formation, its maintenance and associated behaviours from neural and evolutionary
      perspectives.

PMID- 30301955
TI  - Fasting enhances extinction retention and prevents the return of fear in humans.
AB  - Fear is prone to return following extinction that is the basis of exposure
      therapy for fear-related disorders. Manipulations that enhance the extinction
      process can be beneficial for treatment. Animal studies have shown that fasting
      or caloric restriction can enhance extinction and inhibit the return of fear. The
      present study examined the effects of fasting on fear acquisition, extinction,
      and the return of fear in humans. One hundred and twenty-five male participants
      were randomized into a fasting group and food group and exposed to a Pavlovian
      fear conditioning paradigm. Changes in plasma cortisol and ghrelin levels were
      examined using enzyme-linked immunosorbent assays. One-night fasting had no
      effect on fear acquisition but enhanced fear extinction retention and prevented
      the return of fear, and this effect persisted for at least 6 months. This
      procedure was also effective for remote fear memory. Plasma ghrelin levels were
      elevated after fasting and had a negative relationship with the fear response in
      spontaneous recovery test. However, overnight fasting did not affect cortisol
      levels. These findings indicate that fasting enhances extinction retention and
      prevents the return of fear, without influencing fear memory formation. We
      propose that this novel procedure may open new avenues for promoting extinction
      based therapies for fear-related disorders.

PMID- 30301956
TI  - Verbal instructions override the meaning of facial expressions.
AB  - Psychological research has long acknowledged that facial expressions can
      implicitly trigger affective psychophysiological responses. However, whether
      verbal information can alter the meaning of facial emotions and corresponding
      response patterns has not been tested. This study examined emotional facial
      expressions as cues for instructed threat-of-shock or safety, with a focus on
      defensive responding. In addition, reversal instructions were introduced to test
      the impact of explicit safety instructions on fear extinction. Forty participants
      were instructed that they would receive unpleasant electric shocks, for instance,
      when viewing happy but not angry faces. In a second block, instructions were
      reversed (e.g., now angry faces cued shock). Happy, neutral, and angry faces were
      repeatedly presented, and auditory startle probes were delivered in half of the
      trials. The defensive startle reflex was potentiated for threat compared to
      safety cues. Importantly, this effect occurred regardless of whether threat was
      cued by happy or angry expressions. Although the typical pattern of response
      habituation was observed, defense activation to newly instructed threat cues
      remained significantly enhanced in the second part of the experiment, and it was
      more pronounced in more socially anxious participants. Thus, anxious individuals
      did not exhibit more pronounced defense activation compared to less anxious
      participants, but their defense activation was more persistent.

PMID- 30301957
TI  - Exceptional catalytic effects of black phosphorus quantum dots in shuttling-free
      lithium sulfur batteries.
AB  - Lithium sulfur batteries with high energy densities are promising next-generation
      energy storage systems. However, shuttling and sluggish conversion of
      polysulfides to solid lithium sulfides limit the full utilization of active
      materials. Physical/chemical confinement is useful for anchoring polysulfides,
      but not effective for utilizing the blocked intermediates. Here, we employ black
      phosphorus quantum dots as electrocatalysts to overcome these issues. Both the
      experimental and theoretical results reveal that black phosphorus quantum dots
      effectively adsorb and catalyze polysulfide conversion. The activity is
      attributed to the numerous catalytically active sites on the edges of the quantum
      dots. In the presence of a small amount of black phosphorus quantum dots, the
      porous carbon/sulfur cathodes exhibit rapid reaction kinetics and no shuttling of
      polysulfides, enabling a low capacity fading rate (0.027% per cycle over 1000
      cycles) and high areal capacities. Our findings demonstrate application of a
      metal-free quantum dot catalyst for high energy rechargeable batteries.

PMID- 30301958
TI  - The genetic landscape of 5T models for multiple myeloma.
AB  - Murine models for multiple myeloma (MM) are often used to investigate
      pathobiology of multiple myeloma and disease progression. Unlike transgenic mice
      models, where it is known which oncogene is driving MM disease, the somatic
      aberrations of spontaneous syngeneic 5T models of MM have not yet been reported.
      Here, we analyzed the copy-number alterations (CNA) and mutational landscape of
      5T2, 5T33vv and 5TGM1 murine MM models using whole-genome and whole-exome
      sequencing. Forty four percent of the genome of 5T2 cells is affected by CNAs
      while this was only 11% and 17% for 5T33vv and 5TGM1 cells, respectively. We
      found that up to 69% of the genes linked to gain of 1q or deletion of 13q in MM
      patients are present as respectively gains in 5T2 cells or deletions in 5T33 and
      5TGM1 cells. Exome sequencing furthermore revealed mutations of genes involved in
      RAS/MAPK, PI3K/AKT1 and JAK/STAT signaling, DNA damage response, cell cycle,
      epigenetic regulation and extracellular matrix organization. We observed a
      statistically significant overlap of genes mutated in the 5T models and MM
      patients. Overall, the genetic landscape of the 5T models is heterogeneous with a
      high number of aberrations involving genes in various multiple myeloma-related
      pathways.

PMID- 30301960
TI  - Necessity for a paradigm shift in the treatment of pediatric obesity.

PMID- 30301961
TI  - Obesity-associated family with sequence similarity 13, member A (FAM13A) is
      dispensable for adipose development and insulin sensitivity.
AB  - BACKGROUND: Obesity and its associated morbidities represent the major and most
      rapidly expanding world-wide health epidemic. Recent genome-wide association
      studies (GWAS) reveal that single nucleotide polymorphism (SNP) variant in the
      Family with Sequence Similarity 13, Member A (FAM13A) gene is strongly associated
      with waist-hip ratio (WHR) with adjustment for body mass index (BMI) (WHRadjBMI).
      However, the function of FAM13A in adipose development and obesity remains
      largely uncharacterized. METHODS: The expression of FAM13A in adipose tissue
      depots were investigated using lean, genetic obese and high fat diet-induced
      obese (DIO) animal models and during adipocyte differentiation. Stromal vascular
      cells (SVCs) or 3T3-L1 cells with gain and loss of function of FAM13A were used
      to determine the involvement of FAM13A in regulating adipocyte differentiation.
      Adipose development and metabolic homeostasis in Fam13a-/- mice were
      characterized under normal chow and high fat diet feeding. RESULTS: Murine FAM13A
      expression was nutritionally regulated and dramatically reduced in epididymal and
      subcutaneous fat in genetic and diet-induced obesity. Its expression was enriched
      in mature adipocytes and significantly upregulated during murine and human
      adipogenesis potentially through a peroxisome proliferator-activated receptor
      gamma (PPARgamma)-dependent mechanism. However, Fam13a-/- mice only exhibited a
      tendency of higher adiposity and were not protected from DIO and insulin
      resistance. While Fam13a-/- SVCs maintained normal adipogenesis, overexpression
      of FAM13A in 3T3-L1 preadipocytes downregulated beta-catenin signaling and
      rendered preadipocytes more susceptible to apoptosis. Moreover, FAM13A
      overexpression largely blocked adipogenesis induced by a standard hormone
      cocktail, but adipogenesis can be partially rescued by the addition of PPARgamma
      agonist pioglitazone at an early stage of differentiation. CONCLUSIONS: Our
      results suggest that FAM13A is dispensable for adipose development and insulin
      sensitivity. Yet the expression of FAM13A needs to be tightly controlled in
      adipose precursor cells for their proper survival and downstream adipogenesis.
      These data provide novel insights into the link between FAM13A and obesity.

PMID- 30301959
TI  - Persistent platelet activation and apoptosis in virologically suppressed HIV
      infected individuals.
AB  - Cardiovascular diseases and thrombotic events became major clinical problems in
      the combined antiretroviral therapy (cART) era. Although the precise mechanisms
      behind these clinical problems have not been fully elucidated, a persistent pro
      inflammatory state plays a central role. As platelets play important roles on
      both, thrombus formation and inflammatory/immune response, we aimed at
      investigating platelet function in HIV-infected subjects virologically controlled
      through cART. We evaluate parameters of activation, mitochondrial function and
      activation of apoptosis pathways in platelets from 30 HIV-infected individuals
      under stable cART and 36 healthy volunteers. Despite viral control achieved
      through cART, HIV-infected individuals exhibited increased platelet activation as
      indicated by P-selectin expression and platelet spreading when adhered on
      fibrinogen-coated surfaces. Platelets from HIV-infected subjects also exhibited
      mitochondrial dysfunction and activation of apoptosis pathways. Finally, thrombin
      stimuli induced lower levels of P-selectin translocation and RANTES secretion,
      but not TXA2 synthesis, in platelets from HIV-infected individuals compared to
      control; and labeling of platelet alpha granules showed reduced granule content
      in platelets from HIV-infected individuals when compared to healthy subjects. In
      summary, platelets derived from HIV-infected individuals under stable cART
      exhibit a phenotype of increased activation, activation of the intrinsic pathway
      of apoptosis and undermined granule secretion in response to thrombin.

PMID- 30301962
TI  - High-fat diet consumption alters energy metabolism in the mouse hypothalamus.
AB  - BACKGROUND/OBJECTIVES: High-fat diet consumption is known to trigger an
      inflammatory response in the hypothalamus, which has been characterized by an
      initial expression of pro-inflammatory genes followed by hypothalamic
      astrocytosis, microgliosis, and the appearance of neuronal injury markers. The
      specific effects of high-fat diet on hypothalamic energy metabolism and
      neurotransmission are however not yet known and have not been investigated
      before. SUBJECTS/METHODS: We used 1H and 13C magnetic resonance spectroscopy
      (MRS) and immunofluorescence techniques to evaluate in vivo the consequences of
      high-saturated fat diet administration to mice, and explored the effects on
      hypothalamic metabolism in three mouse cohorts at different time points for up to
      4 months. RESULTS: We found that high-fat diet increases significantly the
      hypothalamic levels of glucose (P < 0.001), osmolytes (P < 0.001), and
      neurotransmitters (P < 0.05) from 2 months of diet, and alters the rates of
      metabolic (P < 0.05) and neurotransmission fluxes (P < 0.001), and the
      contribution of non-glycolytic substrates to hypothalamic metabolism (P < 0.05)
      after 10 weeks of high-fat feeding. CONCLUSIONS/INTERPRETATION: We report changes
      that reveal a high-fat diet-induced alteration of hypothalamic metabolism and
      neurotransmission that is quantifiable by 1H and 13C MRS in vivo, and present the
      first evidence of the extension of the inflammation pathology to a localized
      metabolic imbalance.

PMID- 30301963
TI  - Levels of adherence needed to achieve significant weight loss.
AB  - BACKGROUND/OBJECTIVES: Positive associations have been found between adherence
      and weight loss in behavioral weight-management interventions. However, less
      attention has been given to the level of adherence needed to reach clinically
      significant weight loss. This study examined the levels of adherence associated
      with a >= 5% - < 10% or >= 10% weight loss in a community-based, intensive
      behavioral weight management program, Weight Watchers(r) (WW), which included
      three modes of access: (1) 24-weekly WW meetings over 6 months, (2) the WW member
      website, and (3) the WW mobile application. METHODS: A total of 292 participants
      were randomized to a WW (n = 147) or a self-help (SH) (n = 145) condition. To
      assess the impact of adherence, only participants in the WW condition were
      included in analyses (n = 147). Adherence was defined as use of the three modes
      of access. Measured heights and weights were obtained at baseline and 6 months.
      Receiver-operating characteristic curve analyses were conducted to determine the
      minimal level of adherence associated with clinically significant weight loss.
      RESULTS: In a 6-month period, increased likelihood of achieving a weight loss >=
      5% - < 10% was associated with attending approximately one-third (35.4%) of
      weekly meetings, use of the member website about 25% of days, and use of the
      mobile application 16.1% of days. Attendance at approximately two-thirds (64.5%)
      of meetings, use of the member website 41.6% of days, and use of the mobile
      application 14.7% of days were associated with a clinically significant weight
      loss of >= 10%. Meeting attendance was the strongest predictor of weight loss at
      6 months. CONCLUSIONS: Although adherence to a behavioral weight management
      program was an important predictor of weight loss, extremely high levels were not
      needed to achieve clinically significant weight loss. These results are important
      to help patients and treatment providers understand realistic goals for weight
      management.

PMID- 30301964
TI  - Interventions for treating children and adolescents with overweight and obesity:
      an overview of Cochrane reviews.
AB  - Children and adolescents with overweight and obesity are a global health concern.
      This is an integrative overview of six Cochrane systematic reviews, providing an
      up-to-date synthesis of the evidence examining interventions for the treatment of
      children and adolescents with overweight or obesity. The data extraction and
      quality assessments for each review were conducted by one author and checked by a
      second. The six high quality reviews provide evidence on the effectiveness of
      behaviour changing interventions conducted in children <6 years (7 trials), 6-11
      years (70 trials), adolescents 12-17 years (44 trials) and interventions that
      target only parents of children aged 5-11 years (20 trials); in addition to
      interventions examining surgery (1 trial) and drugs (21 trials). Most of the
      evidence was derived from high-income countries and published in the last two
      decades. Collectively, the evidence suggests that multi-component behaviour
      changing interventions may be beneficial in achieving small reductions in body
      weight status in children of all ages, with low adverse event occurrence were
      reported. More research is required to understand which specific intervention
      components are most effective and in whom, and how best to maintain intervention
      effects. Evidence from surgical and drug interventions was too limited to make
      inferences about use and safety, and adverse events were a serious consideration.

PMID- 30301965
TI  - Information bias in measures of self-reported physical activity.

PMID- 30301966
TI  - Genetic background influences weight-loss trajectories on the mid-term after
      bariatric surgery.
AB  - Bariatric surgery (BS) is a highly effective therapy for morbid obesity, yet with
      a wide inter-individual variability on weight-loss responses. To determine
      genetic influence on weight loss after BS we compared the within-pairs difference
      in maximum percentage excess weight loss (%EWL) and the within-pairs %EWL
      differences over a mean follow-up of 53.6 +/- 36.4 months between 47 pairs of
      first-degree relatives and 47 genetically unrelated control pairs. Within-pairs
      maximum %EWL difference was similar between first-degree related pairs and
      control pairs (p = 0.100). Within-pairs %EWL difference increased through follow
      up (p < 0.001). However, effect of time was different depending on genetic
      background (ptime*group = 0.001). Increased variability in mid-term weight
      response was present in unrelated pairs but not in first-degree pairs (p < 0.001
      and p = 0.535, respectively). To assess shared environment influence, 16 married
      couples were identified and 16 unrelated and non-cohabiting matched pairs were
      also analyzed. In these analysis within-pairs difference in %EWL also increase
      over time (p = 0.025) but no group by time effect was observed (ptime*group =
      0.177). In conclusion first-degree related participants showed closer weight
      trajectories after BS time than genetically unrelated subjects. Genetic
      background might partially explain the variability in mid-term weight-loss after
      BS.

PMID- 30301967
TI  - Temporal immmunometabolic profiling of adipose tissue in HFD-induced obesity:
      manifestations of mast cells in fibrosis and senescence.
AB  - BACKGROUND/OBJECTIVES: Chronic low-grade inflammation/meta-inflammation in
      adipose tissue leads to obesity-associated metabolic complications. Despite
      growing understanding, the roles of immune cell subsets, their interrelationship,
      and chronological events leading to progression of obesity-associated insulin
      resistance (IR) remains unclear. METHODS: We carried out temporal immunometabolic
      profiling of adipose tissue from C57BL/6 mice fed a high-fat diet (HFD) for 4, 8,
      12, 16, and 20 weeks. We used clodronate sodium liposomes (CLODs) to deplete
      macrophages and disodium cromoglycate sodium liposomes (DSCGs) to stabilize mast
      cells. RESULTS: In the temporal HFD settings, mice showed progressive glucose
      intolerance, insulin resistance, and adipose tissue senescence. Histochemistry
      analysis of epididymal white adipose tissue (eWAT) using picro-sirius red and
      Masson's trichrome staining showed extensive collagen deposition in the 16th and
      20th weeks. Flow cytometry analysis of the stromal vascular fraction (SVF) from
      eWAT revealed T-cell subsets as early-phase components and pro-inflammatory
      macrophages, as well as mast cells as the later phase components during obesity
      progression. In our therapeutic strategies, macrophage depletion by CLOD and mast
      stabilization by DSCG attenuated obesity, adipose tissue fibrosis, and improved
      whole-body glucose homeostasis. In addition, mast cell stabilization also
      attenuated senescence (p53 and X-gal staining) in eWAT, signifying the role of
      mast cells over macrophages during obesity. CONCLUSION: New-generation mast cell
      stabilizers can be exploited for the treatment of obesity-associated metabolic
      complications.

PMID- 30301968
TI  - Evaluation of chitotriosidase as a biomarker for adipose tissue inflammation in
      overweight individuals and type 2 diabetic patients.
AB  - BACKGROUND: Overweight and obesity can lead to adipose tissue inflammation, which
      causes insulin resistance and on the long-term type 2 diabetes mellitus (T2D).
      The inflammatory changes of obese-adipose tissue are characterized by macrophage
      infiltration and activation, but validated circulating biomarkers for adipose
      tissue inflammation for clinical use are still lacking. One of the most secreted
      enzymes by activated macrophages is chitotriosidase (CHIT1). OBJECTIVE: To test
      whether circulating CHIT1 enzymatic activity levels reflect adipose tissue
      inflammation. METHODS: Plasma and adipose tissue samples of 105 subjects (35
      lean, 37 overweight, and 33 T2D patients) were investigated. CHIT1 mRNA levels
      were determined in adipose tissue-resident innate immune cells. CHIT1 mRNA
      levels, protein abundance, and plasma enzymatic activity were subsequently
      measured in adipose tissue biopsies and plasma of control subjects with varying
      levels of obesity and adipose tissue inflammation as well as in T2D patients.
      RESULTS: In adipose tissue, CHIT1 mRNA levels were higher in stromal vascular
      cells compared to adipocytes, and higher in adipose tissue-residing macrophages
      compared to circulating monocytes (p < 0.001). CHIT1 mRNA levels in adipose
      tissue were enhanced in overweightcompared to lean subjects and even more in T2D
      patients (p < 0.05). In contrast, plasma CHIT1 enzymatic activity did not differ
      between lean, overweight subjects and T2D patients. A mutation of the CHIT1 gene
      decreases plasma CHIT1 activity. CONCLUSIONS: CHIT1 is expressed by adipose
      tissue macrophages and expression is higher in overweight subjects and T2D
      patients, indicating its potential as tissue biomarker for adipose tissue
      inflammation. However, these differences do not translate into different plasma
      CHIT1 activity levels. Moreover, a common CHIT1 gene mutation causing loss of
      plasma CHIT1 activity interferes with its use as a biomarker of adipose tissue
      inflammation. These results indicate that plasma CHIT1 activity is of limited
      value as a circulating biomarker for adipose tissue inflammation in human
      subjects.

PMID- 30301969
TI  - Uncovering association networks through an eQTL analysis involving human miRNAs
      and lincRNAs.
AB  - Non-coding RNAs (ncRNA) have an essential role in the complex landscape of human
      genetic regulatory networks. One area that is poorly explored is the effect of
      genetic variations on the interaction between ncRNA and their targets. By
      integrating a significant amount of public data, the present study cataloged the
      vast landscape of the regulatory effect of microRNAs (miRNA) and long intergenic
      noncoding RNAs (lincRNA) in the human genome. An expression quantitative trait
      loci (eQTL) analysis was used to identify genetic variants associated with miRNA
      and lincRNA and whose genotypes affect gene expression. Association networks were
      built for eQTL associated to traits of clinical and/or pharmacological relevance.

PMID- 30301971
TI  - There's NO limit.

PMID- 30301970
TI  - Replacing the Draize eye test: Impedance spectroscopy as a 3R method to
      discriminate between all GHS categories for eye irritation.
AB  - Highly invasive animal based test procedures for risk assessment such as the
      Draize eye test are under increasing criticism due to poor transferability for
      the human organism and animal-welfare concerns. However, besides all efforts, the
      Draize eye test is still not completely replaced by alternative animal-free
      methods. To develop an in vitro test to identify all categories of eye
      irritation, we combined organotypic cornea models based on primary human cells
      with an electrical readout system that measures the impedance of the test models.
      First, we showed that employing a primary human cornea epithelial cell based
      model is advantageous in native marker expression to the primary human epidermal
      keratinocytes derived models. Secondly, by employing a non-destructive measuring
      system based on impedance spectroscopy, we could increase the sensitivity of the
      test system. Thereby, all globally harmonized systems categories of eye
      irritation could be identified by repeated measurements over a period of 7 days.
      Based on a novel prediction model we achieved an accuracy of 78% with a
      reproducibility of 88.9% to determine all three categories of eye irritation in
      one single test. This could pave the way according to the 3R principle to replace
      the Draize eye test.

PMID- 30301972
TI  - Small RNA-based antimicrobial immunity.
AB  - Protection against microbial infection in eukaryotes is provided by diverse
      cellular and molecular mechanisms. Here, we present a comparative view of the
      antiviral activity of virus-derived small interfering RNAs in fungi, plants,
      invertebrates and mammals, detailing the mechanisms for their production,
      amplification and activity. We also highlight the recent discovery of viral PIWI
      interacting RNAs in animals and a new role for mobile host and pathogen small
      RNAs in plant defence against eukaryotic pathogens. In turn, viruses that infect
      plants, insects and mammals, as well as eukaryotic pathogens of plants, have
      evolved specific virulence proteins that suppress RNA interference (RNAi).
      Together, these advances suggest that an antimicrobial function of the RNAi
      pathway is conserved across eukaryotic kingdoms.

PMID- 30301973
TI  - Publisher Correction: T cells under starter's orders.
AB  - In the 5th paragraph of the originally published version of this Highlight
      article, it was incorrectly stated that AMPK is activated by "a high ATP to AMP
      ratio"; this has now been corrected to a "high AMP to ATP ratio" in the HTML and
      PDF versions.

PMID- 30301975
TI  - Plant probiotic supresses bacterial wilt.

PMID- 30301976
TI  - A useful by-product.

PMID- 30301977
TI  - An expanding fungal tree of life.

PMID- 30301974
TI  - The oral microbiota: dynamic communities and host interactions.
AB  - The dynamic and polymicrobial oral microbiome is a direct precursor of diseases
      such as dental caries and periodontitis, two of the most prevalent microbially
      induced disorders worldwide. Distinct microenvironments at oral barriers harbour
      unique microbial communities, which are regulated through sophisticated
      signalling systems and by host and environmental factors. The collective function
      of microbial communities is a major driver of homeostasis or dysbiosis and
      ultimately health or disease. Despite different aetiologies, periodontitis and
      caries are each driven by a feedforward loop between the microbiota and host
      factors (inflammation and dietary sugars, respectively) that favours the
      emergence and persistence of dysbiosis. In this Review, we discuss current
      knowledge and emerging mechanisms governing oral polymicrobial synergy and
      dysbiosis that have both enhanced our understanding of pathogenic mechanisms and
      aided the design of innovative therapeutic approaches for oral diseases.

PMID- 30301981
TI  - Extraordinary  crystals hold secrets of Earth's infancy.

PMID- 30301980
TI  - Efficient and Sensitive Electrically Small Rectenna for Ultra-Low Power RF Energy
      Harvesting.
AB  - A new electrically small antenna with size ka = 0.415 is presented, fabricated
      and measured in this work. This is intrinsically matched to 50 Omega, has omni
      directional and linear-polarized radiation pattern in the horizontal plane with
      maximum directivity of 1.75 dBi and simulated radiation efficiency of 93%. The
      antenna in combination with a low-complex and co-planar rectifier with one single
      diode forms a high efficient and sensitive electrically small rectenna with ka =
      0.53 at 868 MHz (UHF RFID-band in Europe). The latter has measured efficiency
      22.5% for -19 dBm power input and sensitivity of -44 dBm (or equivalently 0.00028
      MUW/cm2 power density), while at 2.25 MUW/cm2 is able to supply continuously,
      i.e., without a boost converter or use of any energy tank, a small electrical
      device with 118 MUW. In order to increase the dc output voltage and the delivered
      dc power to the load for lower power density levels, rectenna-array configuration
      is exploited. Application to batteryless, backscatter wireless sensor node
      powering is discussed. Specifically, for a power density of 0.1237 MUW/cm2 the RF
      energy harvesting system delivers 172 MUW at 2.85 V every 22.5 s.

PMID- 30301979
TI  - Long non-coding RNA CCRR controls cardiac conduction via regulating intercellular
      coupling.
AB  - Long non-coding RNAs (lncRNAs) have emerged as a new class of gene expression
      regulators playing key roles in many biological and pathophysiological processes.
      Here, we identify cardiac conduction regulatory RNA (CCRR) as an antiarrhythmic
      lncRNA. CCRR is downregulated in a mouse model of heart failure (HF) and in
      patients with HF, and this downregulation slows cardiac conduction and enhances
      arrhythmogenicity. Moreover, CCRR silencing induces arrhythmias in healthy mice.
      CCRR overexpression eliminates these detrimental alterations. HF or CCRR
      knockdown causes destruction of intercalated discs and gap junctions to slow
      longitudinal cardiac conduction. CCRR overexpression improves cardiac conduction
      by blocking endocytic trafficking of connexin43 (Cx43) to prevent its degradation
      via binding to Cx43-interacting protein CIP85, whereas CCRR silence does the
      opposite. We identified the functional domain of CCRR, which can reproduce the
      functional roles and pertinent molecular events of full-length CCRR. Our study
      suggests CCRR replacement a potential therapeutic approach for pathological
      arrhythmias.

PMID- 30301982
TI  - Gone to the dark side: bacteria thrive 600 metres below Earth's surface.

PMID- 30301978
TI  - A missense variant in SLC39A8 is associated with severe idiopathic scoliosis.
AB  - Genetic factors predictive of severe adolescent idiopathic scoliosis (AIS) are
      largely unknown. To identify genetic variation associated with severe AIS, we
      performed an exome-wide association study of 457 severe AIS cases and 987
      controls. We find a missense SNP in SLC39A8 (p.Ala391Thr, rs13107325) associated
      with severe AIS (P = 1.60 * 10-7, OR = 2.01, CI = 1.54-2.62). This pleiotropic
      SNP was previously associated with BMI, blood pressure, cholesterol, and blood
      manganese level. We replicate the association in a second cohort (841 cases and
      1095 controls) resulting in a combined P = 7.02 * 10-14, OR = 1.94, CI = 1.63
      2.34. Clinically, the minor allele of rs13107325 is associated with greater
      spinal curvature, decreased height, increased BMI and lower plasma manganese in
      our AIS cohort. Functional studies demonstrate reduced manganese influx mediated
      by the SLC39A8 p.Ala391Thr variant and vertebral abnormalities, impaired growth,
      and decreased motor activity in slc39a8 mutant zebrafish. Our results suggest the
      possibility that scoliosis may be amenable to dietary intervention.

PMID- 30301983
TI  - Tapeworm DNA hints at discomforts of life in a medieval trading hub.

PMID- 30301984
TI  - ' Test-tube' evolution wins Chemistry Nobel Prize.

PMID- 30301985
TI  - This miniature drug factory fits on a few lab benches.

PMID- 30301986
TI  - Science and the Supreme Court: Cases to watch in 2018.

PMID- 30301987
TI  - Architect of bold European open-access plan heads to Washington to garner US
      support.

PMID- 30301988
TI  - Brazil's presidential election could savage its science.

PMID- 30301989
TI  - Europe eyes fleet of tiny CO2-monitoring satellites to track global emissions.

PMID- 30301990
TI  - Neanderthal liaisons bestowed virus-fighting genes on humans.

PMID- 30301992
TI  - Bionic algae barrel through blood to deliver drugs.

PMID- 30301991
TI  - How to persuade a reluctant metal to take on a superpower.

PMID- 30301993
TI  - From the archive.

PMID- 30301994
TI  - IPCC says limiting global warming to 1.5  degrees C will require drastic action.

PMID- 30301995
TI  - Trolling, hacking and the 2016 US presidential election.

PMID- 30301997
TI  - Peer-reviewed homeopathy study sparks uproar in Italy.

PMID- 30301998
TI  - Fortresses of mud: how to protect the San Francisco Bay Area from rising seas.

PMID- 30301999
TI  - Two Nobels for women - why so slow?

PMID- 30302000
TI  - Nobel committees must do more to achieve equality.

PMID- 30302001
TI  - Governments must take heed of latest IPCC assessment.

PMID- 30302002
TI  - Versatile chemical handling to confine radioactive cesium as stable inorganic
      crystal.
AB  - The present paper describes an extremely efficient, reproducible and inexpensive
      chemical handling method for converting the nuclear wastes contaminated by
      radioactive cesium to stable inorganic crystal, pollucite (CsAlSi2O6), which is
      promising as a form of the final storage. In this processing, the clays are used
      as a source for aluminum and silicon, and it is important to get a well-mixed
      homogenous solution by the aid of some heat and pressure. The present method
      proposes the use of ethylene glycol as a solvent, rather than water. It has been
      found that one can obtain crystalline pollucite by heating up to 350  degrees C
      in a high-pressure container (~15 MPa), mixed with montmorillonite - an abundant
      natural clay and ethylene glycol. It has been found that the reduction of the
      amount of water helps to achieve very high confinement rate in a reasonable time
      of few~20 h. This will be fairly important in processing contaminated water in
      the nuclear power plant. The influence of seawater has been also examined.

PMID- 30302003
TI  - Highly selective transition-metal-free transamidation of amides and amidation of
      esters at room temperature.
AB  - Amide chemistry has an essential role in the synthesis of high value molecules,
      such as pharmaceuticals, natural products, and fine chemicals. Over the past
      years, several examples of transamidation reactions have been reported. In
      general, transition-metal-based catalysts or harsh conditions are employed for
      these transformations due to unfavorable kinetics and thermodynamics of the
      process. Herein, we report a significant advance in this area and present the
      general method for transition-metal-free transamidation of amides and amidation
      of esters by highly selective acyl cleavage with non-nucleophilic amines at room
      temperature. In contrast to metal-catalyzed protocols, the method is
      operationally-simple, environmentally-friendly, and operates under exceedingly
      mild conditions. The practical value is highlighted by the synthesis of valuable
      amides in high yields. Considering the key role of amides in various branches of
      chemical science, we envision that this broadly applicable method will be of
      great interest in organic synthesis, drug discovery, and biochemistry.

PMID- 30302004
TI  - Long-term efficacy and duration of action of dexamethasone implant, in
      vitrectomised and non-vitrectomised eyes with persistent diabetic macular oedema.
AB  - PURPOSE: To evaluate the efficacy and duration of action of an intravitreal
      (dexamethasone (Ozurdex)) implant in vitrectomised and non-vitrectomised eyes
      with persistent diabetic macular oedema (DMO). METHODS: We retrospectively
      analysed the records for 18 eyes that had or had not been vitrectomised but
      required an intravitreal dexamethasone implant for DMO after a poor response to
      anti-vascular endothelial growth factor. Optical coherence tomography and visual
      acuity (VA) examinations were performed before and 1, 3 and 6 months after
      implantation. The six months following implantation constituted one treatment
      round; up to three rounds were studied. RESULTS: Ten of 18 eyes had undergone
      vitrectomy. Best-corrected visual acuity (BCVA) and central macular thickness
      (CMT) were significantly improved by months 1-3 after implantation of the Ozurdex
      device in all rounds of treatment. The BCVA and CMT deteriorated gradually after
      month 3 through to month 6 post implantation. There were no statistically
      significant differences between the vitrectomised and non-vitrectomised groups at
      any time point. When the implantation interval was <6 weeks from the end of each
      treatment round, the improvement in BCVA and CMT was obvious even after 18 months
      of treatment. CONCLUSIONS: Vitrectomy did not have a negative effect on the
      duration of action or efficacy of the Ozurdex implant in patients with persistent
      DMO. The implant started working from the first month after implantation
      regardless of whether vitrectomy had or had not been performed. The maximum
      functional and anatomic improvement was achieved in the first 3 months post
      implantation in all treatment rounds.

PMID- 30302005
TI  - Balance design for robust foliar nutrient diagnosis of "Prata" banana (Musa
      spp.).
AB  - The "Cavendish" and "Prata" subgroups represent respectively 47% and 24% of the
      world banana production. Compared to world average progressing from 10.6 to 20.6
      t ha-1 between 1961 and 2016, and despite sustained domestic demand and the
      introduction of new cultivars, banana yield in Brazil has stagnated around 14.5 t
      ha-1 mainly due to nutrient and water mismanagement. "Prata" is now the dominant
      subgroup in N-E Brazil and is fertigated at high costs. Nutrient balances
      computed as isometric log-ratios (ilr) provide a comprehensive understanding of
      nutrient relationships in the diagnostic leaf at high yield level by combining
      raw concentration data. Although the most appropriate method for multivariate
      analysis of compositional balances may be less efficient due to non-normal data
      distribution and limited nutrient mobility in the plant, robustness of the
      nutrient balance approach could be improved using Box-Cox exponents assigned to
      raw foliar concentrations. Our objective was to evaluate the accuracy of nutrient
      balances to diagnose fertigated "Prata" orchards. The dataset comprised 609
      observations on fruit yields and leaf tissue compositions collected from 2010 to
      2016 in Ceara state, N-E Brazil. Raw nutrient concentration ranges were
      ineffective as diagnostic tool due to considerable overlapping of concentration
      ranges for low- and high-yielding subpopulations at cutoff yield of 40 Mg ha-1.
      Nutrient concentrations were combined into isometric log-ratios (ilr) and
      normalized by Box-Cox corrections between 0 and 1 which may also account for
      restricted nutrient transfer from leaf to fruit. Despite reduced ilr skewness,
      Box-Cox coefficients did not improve model robustness measured as the accuracy of
      the Cate-Nelson partition between yield and the multivariate distance across ilr
      values. Sensitivity was 94%, indicating that low yields are attributable
      primarily to nutrient imbalance. There were 148 false-positive specimens (high
      yield despite nutrient imbalance) likely due to suboptimal nutrition,
      contamination, or luxury consumption. The profitability of "Prata" orchards could
      be enhanced by rebalancing nutrients using ilr standards with no need for Box-Cox
      correction.

PMID- 30302006
TI  - A mechanoelectrical mechanism for detection of sound envelopes in the hearing
      organ.
AB  - To understand speech, the slowly varying outline, or envelope, of the acoustic
      stimulus is used to distinguish words. A small amount of information about the
      envelope is sufficient for speech recognition, but the mechanism used by the
      auditory system to extract the envelope is not known. Several different theories
      have been proposed, including envelope detection by auditory nerve dendrites as
      well as various mechanisms involving the sensory hair cells. We used recordings
      from human and animal inner ears to show that the dominant mechanism for envelope
      detection is distortion introduced by mechanoelectrical transduction channels.
      This electrical distortion, which is not apparent in the sound-evoked vibrations
      of the basilar membrane, tracks the envelope, excites the auditory nerve, and
      transmits information about the shape of the envelope to the brain.

PMID- 30302007
TI  - Changing patterns of adult asthma incidence: results from the National Health
      Insurance Service-National Sample Cohort (NHIS-NSC) database in Korea.
AB  - This study was conducted to assess the changes in the annual incidence of adult
      asthma in Korea where the prevalence of asthma had increased steadily in recent
      decades. A population-based cohort study was conducted using the National Health
      Insurance Service-National Sample Cohort (NHIS-NSC), which consisted of 746,816
      adults aged >20 years between 2004 and 2012. Asthma was defined by two or more
      physician claims on the basis of a primary diagnostic code for asthma and
      administration of asthma medications within 1 year. The incidence rates and
      annual percent change were calculated, and the influence of age and sex on the
      incidence rates was studied. The annual asthma incidence increased from 3.63 in
      2004 to 6.07 per 1,000 person-years in 2008. Since 2008, the asthma incidence did
      not change significantly. The asthma incidence was higher in women than in men
      throughout the study periods (p < 0.001) and higher in older than younger age
      groups (p < 0.001). The asthma incidence did not change in all ages since 2008,
      except for the 20 s who showed a steady increase. The incidence of asthma in
      adults reached plateau in Korea, which is consistent with the results from
      studies in other countries.

PMID- 30302008
TI  - Templated replication (or lack thereof) under prebiotically pertinent conditions.
AB  - Accurate replication of encoded information would have been crucial for the
      formation and propagation of functional ribozymes during the early evolution of
      life. Studies aimed at understanding prebiotically pertinent nonenzymatic
      reactions have predominantly used activated nucleotides. However, the existence
      of concentrated pools of activated monomers on prebiotic Earth is debatable. In
      this study, we explored the feasibility of nonenzymatic copying reactions using
      the more prebiotically relevant 5'-nucleoside monophosphates (5'-NMP). These
      reactions, involving a 20-mer primer, were performed in the presence of
      amphiphiles, under volcanic geothermal conditions. Interestingly, the extended
      primer was not comparable to the expected full length 21-mer product. Our results
      suggest loss of the nitrogenous base in the extended primer. This phenomenon
      persisted even after lowering the temperature and when different rehydration
      solutions were used. We envisage that the loss of the informational moiety on the
      incoming 5'-NMP, might be occurring during addition of this monomer to the pre
      existing oligomer. Significantly, when 5'-ribose monophosphate was used, multiple
      additions to the aforementioned primer were observed that resulted in hybrid
      polymers. Such hybrid oligomers could have been important for exploring a vast
      chemical space of plausible alternate nucleobases, thus having important
      implications for the origin of primitive informational polymers.

PMID- 30302009
TI  - Febrile Temperature Elevates the Expression of Phosphatidylserine on Plasmodium
      falciparum (FCR3CSA) Infected Red Blood Cell Surface Leading to Increased
      Cytoadhesion.
AB  - During the asexual intra-erythrocytic cycle, Plasmodium (P.) falciparum exports
      parasitic proteins to the surface of infected red blood cells (iRBCs)
      facilitating its cytoadhesion to various endothelial host receptors. This
      adhesive behavior is a critical contributor towards disease manifestation.
      However, little is known about the influence of recurring elevated temperature -
      a common symptom of the malaria infection - on the adhesive properties of iRBCs
      to endothelial receptors. To address this, we performed dual-micropipette step
      pressure technique between P. falciparum (strain FCR3CSA) iRBCs and Chinese
      Hamster Ovary cells expressing Chondroitin sulfate A (CHO-CSA) after transient
      iRBCs incubation at febrile temperatures which revealed increase in adhesion
      parameters. Furthermore, flow cytometry analysis revealed an increase in
      phosphatidylserine (PS) expression on the iRBC surface following exposure to
      febrile temperature. The adhesion between iRBCs and CHO-CSA cells was remarkably
      reduced in presence of soluble Annexin V, indicating the mediation of PS on the
      adhesion events. Our results suggest that elevated PS recruitment on iRBC under
      thermally stressed conditions contributes to the increased adhesive behavior of
      iRBCs CSA-binding phenotype to CHO-CSA.

PMID- 30302010
TI  - PLA2G6-associated neurodegeneration presenting as a complicated form of
      hereditary spastic paraplegia.
AB  - PLA2G6-associated neurodegeneration (PLAN) comprises heterogeneous
      neurodegenerative disorders, including infantile neuroaxonal dystrophy,
      neurodegeneration with brain iron accumulation 2B, and Parkinson disease 14
      (PARK14). In addition, very recently, PLA2G6 mutations have been reported to
      represent a phenotype of hereditary spastic paraplegia (HSP). In this study, we
      screened 383 HSP families to clarify the frequency of PLA2G6 mutations in the
      Japan Spastic Paraplegia Research Consortium, and revealed the clinical
      characteristics of HSP with PLA2G6 mutations. We found three families with
      compound heterozygous mutations of the PLA2G6 gene, c.517 C > T/c.1634A > G,
      c.662 T > C/c.991 G > T, and c.1187-2 A > G/c.1933C > T, and one family with a
      homozygous mutation of the PLA2G6 gene, c.1904G > A/c.1904G > A. All three
      families with compound heterozygous mutations presented a uniform phenotype of a
      complicated form of HSP with infantile/child-onset spastic paraplegia, cerebellar
      ataxia, and mental retardation. On the other hand, the family with a homozygous
      mutation presented a late-onset complicated form of HSP with parkinsonism. This
      study may extend the clinical and genetic findings for PLAN.

PMID- 30302011
TI  - Structural Rearrangements Maintain the Glycan Shield of an HIV-1 Envelope Trimer
      After the Loss of a Glycan.
AB  - The HIV-1 envelope (Env) glycoprotein is the primary target of the humoral immune
      response and a critical vaccine candidate. However, Env is densely glycosylated
      and thereby substantially protected from neutralisation. Importantly, glycan N301
      shields V3 loop and CD4 binding site epitopes from neutralising antibodies. Here,
      we use molecular dynamics techniques to evaluate the structural rearrangements
      that maintain the protective qualities of the glycan shield after the loss of
      glycan N301. We examined a naturally occurring subtype C isolate and its N301A
      mutant; the mutant not only remained protected against neutralising antibodies
      targeting underlying epitopes, but also exhibited an increased resistance to the
      VRC01 class of broadly neutralising antibodies. Analysis of this mutant revealed
      several glycans that were responsible, independently or through synergy, for the
      neutralisation resistance of the mutant. These data provide detailed insight into
      the glycan shield's ability to compensate for the loss of a glycan, as well as
      the cascade of glycan movements on a protomer, starting at the point mutation,
      that affects the integrity of an antibody epitope located at the edge of the
      diminishing effect. These results present key, previously overlooked,
      considerations for HIV-1 Env glycan research and related vaccine studies.

PMID- 30302012
TI  - Peptide-oligonucleotide conjugates exhibiting pyrimidine-X cleavage specificity
      efficiently silence miRNA target acting synergistically with RNase H.
AB  - Taking into account the important role of miRNA in carcinogenesis, oncogenic
      miRNAs are attractive molecules for gene-targeted therapy. Here, we developed a
      novel series of peptide-oligonucleotide conjugates exhibiting ribonuclease
      activity targeted to highly oncogenic miRNAs miR-21 and miR-17. When designing
      the conjugates, we enhanced both nuclease resistance of the targeted
      oligodeoxyribonucleotide by introducing at its 3'-end mini-hairpin structure
      displaying high thermostability and robustness against nuclease digestion and the
      efficiency of its functioning by attachment of the catalytic construction
      (amide)NH2-Gly(ArgLeu)4-TCAA displaying ribonuclease activity to its 5'-end.
      Designed miRNases efficiently cleaved miRNA targets, exhibiting Pyr-X
      specificity, and cleavage specificity had strong dependence on the miRNA sequence
      in the site of peptide location. In vitro, designed miRNases do not prevent
      cleavage of miRNA bound with the conjugate by RNase H, and more than an 11-fold
      enhancement of miRNA cleavage by the conjugate is observed in the presence of
      RNase H. In murine melanoma cells, miRNase silences mmu-miR-17 with very high
      efficiency as a result of miR-17 cleavage by miRNase and by recruited RNase H.
      Thus, miRNases provide a system of double attack of the miRNA molecules,
      significantly increasing the efficiency of miRNA downregulation in the cells in
      comparison with antisense oligonucleotide.

PMID- 30302014
TI  - Verifying locations of sources of historical environmental releases of dioxin
      like compounds in the U.S.: implications for exposure assessment and
      epidemiologic inference.
AB  - Polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) emissions from
      industrial sources contaminate the surrounding environment. Proximity-based
      exposure surrogates assume accuracy in the location of PCDD/F sources, but
      locations are not often verified. We manually reviewed locations (i.e.,
      smokestack geo-coordinates) in a historical database of 4478 PCDD/F-emitting
      facilities in 2009 and 2016. Given potential changes in imagery and other
      resources over this period, we re-reviewed a random sample of 5% of facilities (n
      = 240) in 2016. Comparing the original and re-review of this sample, we evaluated
      agreement in verification (location confirmed or not) and distances between
      verified locations (verification error), overall and by facility type. Using the
      verified location from re-review as a gold standard, we estimated the accuracy of
      proximity-based exposure metrics and epidemiologic bias. Overall agreement in
      verification was high (>84%), and verification errors were small (median = 84 m)
      but varied by facility type. Accuracy of exposure classification (>=1 facility
      within 5 km) for a hypothetical study population also varied by facility type
      (sensitivity: 69-96%; specificity: 95-98%). Odds ratios were attenuated 11-69%,
      with the largest bias for rare facility types. We found good agreement between
      reviews of PCDD/F source locations, and that exposure prevalence and facility
      type may influence associations with exposures derived from this database. Our
      findings highlight the need to consider location error and other contextual
      factors when using proximity-based exposure metrics.

PMID- 30302013
TI  - Porcine Reproductive and Respiratory Syndrome Virus strains with Higher Virulence
      Cause Marked Protein Profile Changes in MARC-145 Cells.
AB  - Porcine reproductive and respiratory syndrome is an infectious disease that
      causes serious economic losses to the swine industry worldwide. To better
      understand the pathogenesis of the porcine reproductive and respiratory syndrome
      virus (PRRSV), three PRRSV strains with different molecular markers and virulence
      were used to infect MARC-145 cells. A total of 1804 proteins were identified, and
      233 altered proteins and 72 signaling pathways involved in the proteomic
      profiling of virus-infected MARC-145 cells increased with the virulence of the
      PRRSV strain. The three types of viral strains shared a common pathway-the
      electron transport reaction in mitochondria-in the infected-MARC-145 cells.
      Moreover, the antisense pathway was the most variable of all significant
      signaling pathways for the highly virulent SX-1 strain, indicating that this
      unique pathway may be connected to the high virulence of the SX-1 strain. Our
      study is the first attempt to provide a proteome profile of MARC-145 cells
      infected with PRRSV strains with different virulence, and these findings will
      facilitate a deep understanding of the interactions between this virus and its
      host.

PMID- 30302015
TI  - Alleviation of impaired reactivity in the corpus cavernosum of STZ-diabetic rats
      by slow-release H2S donor GYY4137.
AB  - GYY4137 is a novel hydrogen sulfide (H2S) releasing molecule with vasodilator
      activity. The objectives of this study were to investigate: (1) the
      pharmacological effect of GYY4137 on the reactivity of the corpus cavernosum (CC)
      from normal and diabetic rats; (2) the contribution of ATP-sensitive potassium (K
      ATP) channels and nitric oxide (NO) pathway; (3) the reactivity to vasoactive
      agonists following ex vivo incubation of the diabetic rat CC with GYY4137.
      Longitudinal strips of CC from control and diabetic male Sprague-Dawley (SD) rats
      (n = 5-6 animals per group) were suspended in organ-baths. Responses to GYY4137,
      carbachol, or phenylephrine (PE) were determined by measurement of changes in
      isometric tension. The effects of acute incubation of the CC strips with L-NAME
      (NO synthase inhibitor) or glibenclamide (K-ATP channel inhibitor) on the
      relaxant responses to GYY4137 were examined. The effect of ex vivo incubation
      with GYY4137 (10-5 M) on the responses of CC to carbachol or PE was evaluated. We
      found that GYY4137 provoked relaxation in the CC strips, which was significantly
      reduced in the presence of L-NAME or glibenclamide. Ex vivo incubation of
      diabetic CC with GYY4137 resulted in a significant improvement in the vascular
      responses to the added agonists. We conclude that GYY4137 is a relaxant agonist
      in SD rats CC, and the response is mediated, at least in part, by NO and K-ATP
      channels. Brief incubation of diabetic CC with GYY4137 markedly improved the
      impaired vascular reactivity, thus raising the question whether chronic in vivo
      treatment of diabetic animals with GYY4137 would have any protective effect,
      which is worth further investigation.

PMID- 30302016
TI  - Nitazoxanide, an antiprotozoal drug, inhibits late-stage autophagy and promotes
      ING1-induced cell cycle arrest in glioblastoma.
AB  - Glioblastoma is the most common and aggressive primary brain tumor in adults. New
      drug design and development is still a major challenge for glioma treatment.
      Increasing evidence has shown that nitazoxanide, an antiprotozoal drug, has a
      novel antitumor role in various tumors and exhibits multiple molecular functions,
      especially autophagic regulation. However, whether nitazoxanide-associated
      autophagy has an antineoplastic effect in glioma remains unclear. Here, we aimed
      to explore the underlying molecular mechanism of nitazoxanide in glioblastoma.
      Our results showed that nitazoxanide suppressed cell growth and induced cell
      cycle arrest in glioblastoma by upregulating ING1 expression with a favorable
      toxicity profile. Nitazoxanide inhibited autophagy through blockage of late-stage
      lysosome acidification, resulting in decreased cleavage of ING1. A combination
      with chloroquine or Torin1 enhanced or impaired the chemotherapeutic effect of
      nitazoxanide in glioblastoma cells. Taken together, these findings indicate that
      nitazoxanide as an autophagy inhibitor induces cell cycle arrest in glioblastoma
      via upregulated ING1 due to increased transcription and decreased post
      translational degradation by late-stage autophagic inhibition.

PMID- 30302017
TI  - Using long term mortality to determine which perioperative risk factors of
      mortality following hip and knee replacement may be causal.
AB  - Observational studies have identified surgical factors that are associated with a
      reduced risk of mortality after joint replacement. It is not clear whether these
      are causal or reflect patient selection. Data on the first primary hip (n =
      424,156) and knee replacements (n = 469,989) performed for osteoarthritis in the
      National Joint Registry were analysed. Flexible parametric survival modelling was
      used to determine if risk factors for mortality in the perioperative period
      persisted. To explore selection bias, standardised mortality ratios were
      calculated for all-cause, respiratory and smoking related cancer mortality using
      population rates. Selection was apparent for hip resurfacing, combined spinal and
      general anaesthetic and unicondylar knee implants; reduced mortality was observed
      for many years for both all and other causes of mortality with a waning effect.
      Mechanical thromboprophylaxis was also suggestive of selection although patients
      receiving aspirin had sustained reduced mortality, possibly due to to a
      cardioprotective effect. Posterior approach for hips was ambiguous with a
      possible causal component. Spinal anaesthesia was suggestive of a causal effect.
      We are reliant on observational data when it is not feasible to undertake
      randomised trials. Our approach of looking at long term mortality risks for
      perioperative interventions provides further insights to differentiate causal
      interventions from selection. We recommend the use of aspirin
      chemothromboprophylaxis, the posterior approach and spinal anaesthetic in total
      hip replacement due to the apparent causal effect on reduced mortality.

PMID- 30302019
TI  - Tracking Tumor Colonization in Xenograft Mouse Models Using Accelerator Mass
      Spectrometry.
AB  - Here we introduce an Accelerator Mass Spectrometry (AMS)-based high precision
      method for quantifying the number of cancer cells that initiate metastatic
      tumors, in xenograft mice. Quantification of 14C per cell prior to injection into
      animals, and quantification of 14C in whole organs allows us to extrapolate the
      number of cancer cells available to initiate metastatic tumors. The 14C labeling
      was optimized such that 1 cancer cell was detected among 1 million normal cells.
      We show that ~1-5% of human cancer cells injected into immunodeficient mice form
      subcutaneous tumors, and even fewer cells initiate metastatic tumors. Comparisons
      of metastatic site colonization between a highly metastatic (PC3) and a non
      metastatic (LnCap) cell line showed that PC3 cells colonize target tissues in
      greater quantities at 2 weeks post-delivery, and by 12 weeks post-delivery no 14C
      was detected in LnCap xenografts, suggesting that all metastatic cells were
      cleared. The 14C-signal correlated with the presence and the severity of
      metastatic tumors. AMS measurements of 14C-labeled cells provides a highly
      sensitive, quantitative assay to experimentally evaluate metastasis and
      colonization of target tissues in xenograft mouse models. This approach can
      potentially be used to evaluate tumor aggressiveness and assist in making
      informed decisions regarding treatment.

PMID- 30302018
TI  - The disparate effects of bacteriophages on antibiotic-resistant bacteria.
AB  - Faced with the crisis of multidrug-resistant bacteria, bacteriophages, viruses
      that infect and replicate within bacteria, have been reported to have both
      beneficial and detrimental effects with respect to disease management.
      Bacteriophages (phages) have important ecological and evolutionary impacts on
      their bacterial hosts and have been associated with therapeutic use to kill
      bacterial pathogens, but can lead to the transmission of antibiotic resistance.
      Although the process known as transduction has been reported for many bacterial
      species by classic and modern genetic approaches, its contribution to the spread
      of antibiotic resistance in nature remains unclear. In addition, detailed
      molecular studies have identified phages residing in bacterial genomes, revealing
      unexpected interactions between phages and their bacterial hosts. Importantly,
      antibiotics can induce the production of phages and phage-encoded products,
      disseminating these viruses and virulence-related genes, which have dangerous
      consequences for disease severity. These unwanted side-effects of antibiotics
      cast doubt on the suitability of some antimicrobial treatments and may require
      new strategies to prevent and limit the selection for virulence. Foremost among
      these treatments is phage therapy, which could be used to treat many bacterial
      infectious diseases and confront the pressing problem of antibiotic resistance in
      pathogenic bacteria. This review discusses the interactions between
      bacteriophages, antibiotics, and bacteria and provides an integrated perspective
      that aims to inspire the development of successful antibacterial therapies.

PMID- 30302020
TI  - Transformation of amorphous calcium phosphate to bone-like apatite.
AB  - Mineralisation of calcium phosphates in bone has been proposed to proceed via an
      initial amorphous precursor phase which transforms into nanocrystalline,
      carbonated hydroxyapatite. While calcium phosphates have been under intense
      investigation, the exact steps during the crystallisation of spherical amorphous
      particles to platelet-like bone apatite are unclear. Herein, we demonstrate a
      detailed transformation mechanism of amorphous calcium phosphate spherical
      particles to apatite platelet-like crystals, within the confined nanodomains of a
      bone-inspired nanocomposite. The transformation is initiated under the presence
      of humidity, where nanocrystalline areas are formed and crystallisation advances
      via migration of nanometre sized clusters by forming steps at the growth front.
      We propose that such transformation is a possible crystallisation mechanism and
      is characteristic of calcium phosphates from a thermodynamic perspective and
      might be unrelated to the environment. Our observations provide insight into a
      crucial but unclear stage in bone mineralisation, the origins of the
      nanostructured, platelet-like bone apatite crystals.

PMID- 30302021
TI  - Involvement of anterior and posterior corneal surface area imbalance in the
      pathological change of keratoconus.
AB  - Keratoconus (KC) is an ectatic disorder with a high prevalence rate. However, the
      exact cause of the disease and possible underlying mechanisms of development
      remain unclear. In this present study, we aimed to investigate the anterior and
      the posterior corneal surface area in normal, forme fruste keratoconus (FFKC),
      and keratoconic eyes (as a reference group) using anterior segment optical
      coherence tomography (AS-OCT) in order to assess the pathological change of KC.
      The surface areas of the anterior or posterior cornea, and the anterior-posterior
      (As/Ps) ratio of corneal surface area, were measured at the central 5.0 mm-, 6.0
      mm-, and 7.0 mm-diameter areas via AS-OCT, and a comparison between the normal
      eyes and FFKC eyes was then performed using the Mann-Whitney U test. The
      posterior surface area at the central 5.0 mm areas in the FFKC eyes (20.430 mm2)
      and KC eyes (20.917 mm2) seemed to become larger than that of normal eyes (20.389
      mm2) (normal vs FFKC; P = 0.06). Moreover, the As/Ps of the corneal surface area
      in the FFKC eyes (0.986) and the KC eyes (0.976) was significantly smaller than
      that of the normal eyes (0.988) (normal vs FFKC; P < 0.01). Anterior and
      posterior corneal surface area imbalance may reflect keratoconic eyes at the
      early stage of the disease.

PMID- 30302022
TI  - An HER3-targeting antibody-drug conjugate incorporating a DNA topoisomerase I
      inhibitor U3-1402 conquers EGFR tyrosine kinase inhibitor-resistant NSCLC.
AB  - EGFR tyrosine kinase inhibitors (TKIs) are standard therapy for EGFR-mutant non
      small cell lung cancer (NSCLC); however, these tumours eventually acquire
      chemoresistance. U3-1402 is an anti-HER3 antibody-drug conjugate with a novel
      topoisomerase I inhibitor, DXd. In the current study, we evaluated the anticancer
      efficacy of U3-1402 in EGFR-mutant NSCLC cells with acquired resistance to EGFR
      TKIs. HCC827GR5 and PC9AZDR7 are EGFR-TKI-resistant clones for gefitinib and
      osimertinib, respectively. U3-1402 alone or in combination with the EGFR-TKI
      erlotinib demonstrated potent anticancer efficacy in HCC827GR5 cells using an in
      vitro growth inhibition assay and in vivo xenograft mouse model. U3-1402 induced
      apoptosis in HCC827GR5 cells accompanying phosphorylation of histone H2A.X, a
      marker of DNA damage, but did not block HER3/PI3K/AKT signalling. Further, we
      found using flow cytometry that the cell surface HER3 expression level in
      HCC827GR5 cells was twice that found in HCC827 cells, indicating internalization
      of U3-1402 was increased in resistant cells. In addition, administration of U3
      1402 notably repressed growth of EGFR-TKI osimertinib-resistant PC9AZDR7
      xenograft tumours, and that PC9AZDR7 cells expressed five times greater cell
      surface HER3 than PC9 cells. Furthermore, using immunofluorescent microscopy,
      HER3 was observed predominantly in the nucleus of PC9 cells, but was localized in
      the cytoplasm of PC9AZDR7 cells. This finding indicates that altered trafficking
      of the HER3-U3-1402 complex may accelerate linker payload cleavage by cytoplasmic
      lysosomal enzymes, resulting in DNA damage. Our results indicate that
      administration of U3-1402 alone or in combination with an EGFR-TKI may have
      potential as a novel therapy for EGFR-TKI-resistant EGFR-mutant NSCLC.

PMID- 30302023
TI  - The antioxidant transcription factor Nrf2 modulates the stress response and
      phenotype of malignant as well as premalignant pancreatic ductal epithelial cells
      by inducing expression of the ATF3 splicing variant DeltaZip2.
AB  - Pancreatic ductal adenocarcinoma (PDAC) exhibits one of the worst survival rates
      of all cancers. While death rates show declining trends in the majority of
      cancers, PDAC registers rising rates. Based on the recently described crosstalk
      between TGF-beta1 and Nrf2 in the PDAC development, the involvement of ATF3 and
      its splice variant DeltaZip2 in TGF-beta1- and Nrf2-driven pancreatic
      tumorigenesis was investigated. As demonstrated here, PDAC (Panc1, T3M4) cells or
      premalignant H6c7 pancreatic ductal epithelial cells differentially express
      DeltaZip2- and ATF3, relating to stronger Nrf2 activity seen in Panc1 cells and
      TGF-beta1 activity in T3M4 or H6c7 cells, respectively. Treatment with the
      electrophile/oxidative stress inducer tBHQ or the cytostatic drug gemcitabine
      strongly elevated DeltaZip2 expression in a Nrf2-dependent fashion. The
      differential expression of ATF3 and DeltaZip2 in response to Nrf2 and TGF-beta1
      relates to differential ATF3-gene promoter usage, giving rise of distinct splice
      variants. Nrf2-dependent DeltaZip2 expression confers resistance against
      gemcitabine-induced apoptosis, only partially relating to interference with ATF3
      and its proapoptotic activity, e.g., through CHOP-expression. In fact, DeltaZip2
      autonomously activates expression of cIAP anti-apoptotic proteins. Moreover,
      DeltaZip2 favors and ATF3 suppresses growth and clonal expansion of PDAC cells,
      again partially independent of each other. Using a Panc1 tumor xenograft model in
      SCID-beige mice, the opposite activities of ATF3 and DeltaZip2 on tumor-growth
      and chemoresistance were verified in vivo. Immunohistochemical analyses confirmed
      DeltaZip2 and Nrf2 coexpression in cancerous and PanIN structures of human PDAC
      and chronic pancreatitis tissues, respectively, which to some extent was
      reciprocal to ATF3 expression. It is concluded that depending on selective ATF3
      gene promoter usage by Nrf2, the DeltaZip2 expression is induced in response to
      electrophile/oxidative (here through tBHQ) and xenobiotic (here through
      gemcitabine) stress, providing apoptosis protection and growth advantages to
      pancreatic ductal epithelial cells. This condition may substantially add to
      pancreatic carcinogenesis driven by chronic inflammation.

PMID- 30302024
TI  - Superiority of SpiroZin2 Versus FluoZin-3 for monitoring vesicular Zn2+ allows
      tracking of lysosomal Zn2+ pools.
AB  - Small-molecule fluorescent probes are powerful and ubiquitous tools for measuring
      the concentration and distribution of analytes in living cells. However, accurate
      characterization of these analytes requires rigorous evaluation of cell-to-cell
      heterogeneity in fluorescence intensities and intracellular distribution of
      probes. In this study, we perform a parallel and systematic comparison of two
      small-molecule fluorescent vesicular Zn2+ probes, FluoZin-3 AM and SpiroZin2, to
      evaluate each probe for measurement of vesicular Zn2+ pools. Our results reveal
      that SpiroZin2 is a specific lysosomal vesicular Zn2+ probe and affords uniform
      measurement of resting Zn2+ levels at the single cell level with proper
      calibration. In contrast, FluoZin-3 AM produces highly variable fluorescence
      intensities and non-specifically localizes in the cytosol and multiple vesicular
      compartments. We further applied SpiroZin2 to lactating mouse mammary epithelial
      cells and detected a transient increase of lysosomal free Zn2+ at 24-hour after
      lactation hormone treatment, which implies that lysosomes play a role in the
      regulation of Zn2+ homeostasis during lactation. This study demonstrates the need
      for critical characterization of small-molecule fluorescent probes to define the
      concentration and localization of analytes in different cell populations, and
      reveals SpiroZin2 to be capable of reporting diverse perturbations to lysosomal
      Zn2+.

PMID- 30302025
TI  - AIMP3 Deletion Induces Acute Radiation Syndrome-like Phenotype in Mice.
AB  - Genomes are mostly protected from constant DNA-damaging threats, either internal
      or external, which ultimately sustain the organism. Herein, we report that AIMP3,
      a previously demonstrated tumour suppressor, plays an essential role in
      maintaining genome integrity in adult mice. Upon induction of the temporal
      systemic deletion of AIMP3 by tamoxifen in adult mice, the animals developed an
      acute radiation syndrome-like phenotype, typified by scleroderma, hypotrophy of
      haematopoietic cells and organs, and intestinal failure. Induction of gammaH2AX,
      an early marker of DNA double-strand breaks, was observed in the spleen,
      intestine, and the highly replicating embryonic cortex. In addition, sub-lethal
      irradiation of AIMP3 mKO mice dramatically affected organ damage and survival.
      Using isolated MEFs from conditional KO mice or AIMP3 knockdown cells, we
      confirmed the presence of spontaneously occurring DNA double-strand breaks by
      COMET assay and gammaH2AX induction. Furthermore, gammaH2AX removal was delayed,
      and homologous DNA repair activity was significantly reduced. Reduction of RPA
      foci formation and subsequent Rad51 foci formation probably underlie the
      significant reduction in homologous recombination activity in the absence of
      AIMP3. Together, our data demonstrate that AIMP3 plays a role in genome stability
      through the DNA repair process.

PMID- 30302026
TI  - Carbon stocks and accumulation rates in Red Sea seagrass meadows.
AB  - Seagrasses play an important role in climate change mitigation and adaptation,
      acting as natural CO2 sinks and buffering the impacts of rising sea level.
      However, global estimates of organic carbon (Corg) stocks, accumulation rates and
      seafloor elevation rates in seagrasses are limited to a few regions, thus
      potentially biasing global estimates. Here we assessed the extent of soil Corg
      stocks and accumulation rates in seagrass meadows (Thalassia hemprichii, Enhalus
      acoroides, Halophila stipulacea, Thalassodendrum ciliatum and Halodule uninervis)
      from Saudi Arabia. We estimated that seagrasses store 3.4 +/- 0.3 kg Corg m-2 in
      1 m-thick soil deposits, accumulated at 6.8 +/- 1.7 g Corg m-2 yr-1 over the last
      500 to 2,000 years. The extreme conditions in the Red Sea, such as nutrient
      limitation reducing seagrass growth rates and high temperature increasing soil
      respiration rates, may explain their relative low Corg storage compared to
      temperate meadows. Differences in soil Corg storage among habitats (i.e. location
      and species composition) are mainly related to the contribution of seagrass
      detritus to the soil Corg pool, fluxes of Corg from adjacent mangrove and tidal
      marsh ecosystems into seagrass meadows, and the amount of fine sediment
      particles. Seagrasses sequester annually around 0.8% of CO2 emissions from fossil
      fuels by Saudi Arabia, while buffering the impacts of sea level rise. This study
      contributes data from understudied regions to a growing dataset on seagrass
      carbon stocks and sequestration rates and further evidences that even small
      seagrass species store Corg in coastal areas.

PMID- 30302027
TI  - An innovative flow cytometry method to screen human scFv-phages selected by in
      vivo phage-display in an animal model of atherosclerosis.
AB  - Atherosclerosis is a chronic, progressive inflammatory disease that may develop
      into vulnerable lesions leading to thrombosis. This pathology is characterized by
      the deposition of lipids within the arterial wall and infiltration of immune
      cells leading to amplification of inflammation. Nowadays there is a rising
      interest to assess directly the molecular and cellular components that underlie
      the clinical condition of stroke and myocardial infarction. Single chain fragment
      variable (scFv)-phages issuing from a human combinatorial library were selected
      on the lesions induced in a rabbit model of atherosclerosis after three rounds of
      in vivo phage display. We further implemented a high-throughput flow cytometry
      method on rabbit protein extracts to individually test one thousand of scFv
      phages. Two hundred and nine clones were retrieved on the basis of their
      specificity for atherosclerotic proteins. Immunohistochemistry assays confirmed
      the robustness of the designed cytometry protocol. Sequencing of candidates
      demonstrated their high diversity in VH and VL germline usage. The large number
      of candidates and their diversity open the way in the discovery of new
      biomarkers. Here, we successfully showed the capacity of combining in vivo phage
      display and high-throughput cytometry strategies to give new insights in in vivo
      targetable up-regulated biomarkers in atherosclerosis.

PMID- 30302028
TI  - Molecular signalling towards mitochondrial breakdown is enhanced in skeletal
      muscle of patients with chronic obstructive pulmonary disease (COPD).
AB  - Loss of skeletal muscle mitochondrial oxidative capacity is well-established in
      patients with COPD, but the role of mitochondrial breakdown herein is largely
      unexplored. Currently, we studied if mitochondrial breakdown signalling is
      increased in skeletal muscle of COPD patients and associates with the loss of
      mitochondrial content, and whether it is affected in patients with iron
      deficiency (ID) or systemic inflammation. Therefore, mitophagy, autophagy,
      mitochondrial dynamics and content markers were analysed in vastus lateralis
      biopsies of COPD patients (N = 95, FEV1% predicted: 39.0 [31.0-53.6]) and healthy
      controls (N = 15, FEV1% predicted: 112.8 [107.5-125.5]). Sub-analyses were
      performed on patients stratified by ID or C-reactive protein (CRP). Compared with
      controls, COPD patients had lower muscle mitochondrial content, higher BNIP3L and
      lower FUNDC1 protein, and higher Parkin protein and gene-expression. BNIP3L and
      Parkin protein levels inversely correlated with mtDNA/gDNA ratio and FEV1%
      predicted. ID-COPD patients had lower BNIP3L protein and higher BNIP3 gene
      expression, while high CRP patients had higher BNIP3 and autophagy-related
      protein levels. In conclusion, our data indicates that mitochondrial breakdown
      signalling is increased in skeletal muscle of COPD patients, and is related to
      disease severity and loss of mitochondrial content. Moreover, systemic
      inflammation is associated with higher BNIP3 and autophagy-related protein
      levels.

PMID- 30302029
TI  - Morphological changes, nitric oxide production, and phagocytosis are triggered in
      vitro in microglia by bloodstream forms of Trypanosoma brucei.
AB  - The flagellated parasite Trypanosoma brucei is the causative agent of Human
      African Trypanosomiasis (HAT). By a mechanism not well understood yet,
      trypanosomes enter the central nervous system (CNS), invade the brain parenchyma,
      and cause a fatal encephalopathy if is not treated. Trypanosomes are fast
      dividing organisms that, without any immune response, would kill the host in a
      short time. However, infected individuals survive either 6-12 months or more than
      3 years for the acute and chronic forms, respectively. Thus, only when the brain
      defense collapses a lethal encephalopathy will occur. Here, we evaluated
      interactions between trypanosomes and microglial cells, which are the primary
      immune effector cells within the CNS. Using co-cultures of primary microglia and
      parasites, we found clear evidences of trypanosome phagocytosis by microglial
      cells. Microglia activation was also evident; analysis of its ultrastructure
      showed changes that have been reported in activated microglia undergoing
      oxidative stress caused by infections or degenerative diseases. Accordingly, an
      increase of the nitric oxide production was detected in supernatants of
      microglia/parasite co-cultures. Altogether, our results demonstrate that
      microglial cells respond to the presence of the parasite, leading to parasite's
      engulfment and elimination.

PMID- 30302030
TI  - Effects of PTH on bone composition.

PMID- 30302031
TI  - Pelvic sexual dimorphism among species monomorphic in body size: relationship to
      relative newborn body mass.
AB  - Females have larger pelves than males among eutherians to mitigate obstetrical
      difficulty. This study addresses 3 issues concerning pelvic sexual dimorphism
      using 8 species that are sexually monomorphic in nonpelvic size: Aotus azarae ,
      Castor canadensis , Dasypus novemcinctus , Hylobates lar , Saguinus geoffroyi ,
      Sciurus carolinensis , Sylvilagus floridanus , and Urocyon cinereoargenteus .
      Using published data to compute the index of relative newborn body mass (RNBM =
      [newborn body mass/adult female body mass]100%) for 266 eutherian species, A.
      azarae , H. lar , and S. geoffroyi are characterized as giving birth to
      relatively large newborns and the other 5 species as giving birth to relatively
      small newborns. The 3 issues are, compared to species giving birth to relatively
      small newborns, whether species that give birth to relatively large newborns have
      1) higher magnitude of pelvic sexual size dimorphism (SSD), 2) lower prevalence
      of pelvic joint fusion, and 3) dissociation between pelvic and nonpelvic sizes.
      Nine measures of the pelvis were taken, and fusion of interpubic and sacroiliac
      joints was observed. Species grouped by high and low RNBM do not differ
      significantly in magnitude of SSD of pelvic inlet circumference. Species with
      high RNBM have significantly lower prevalence of interpubic joint fusion than
      those with low RNBM. Sexes do not differ in their multiple correlation
      coefficients between inlet circumference and nonpelvic body size in 7 of 8
      species. Results suggest that 1) there are multiple anatomical pathways for
      pelvic obstetrical sufficiency, 2) an unfused interpubic joint is obstetrically
      advantageous, and 3) relative newborn size does not change the association
      between pelvic and nonpelvic size in females and males.

PMID- 30302032
TI  - Limited and fitness-neutral effects of resource heterogeneity on sociality in a
      communally rearing rodent.
AB  - Contrasting scenarios have been proposed to explain how resource heterogeneity
      influences group living or sociality. First, sociality may result from
      individuals in larger groups attaining net fitness benefits by monopolizing
      access to resources ("resource-defense" hypothesis). Second, sociality may be the
      fitness-neutral outcome of multiple individuals using a territory with sufficient
      resources to sustain a group of conspecifics ("resource-dispersion" hypothesis).
      While previous studies have tended to support the resource-dispersion hypothesis,
      these analyses have typically examined only 1 or a few predictions, making it
      difficult to distinguish between the 2 alternatives. We conducted a 4-year field
      study of Octodon degus to quantify the effects of spatial heterogeneity in food
      and refuge distributions on group size and 2 components of reproductive success
      (per capita number of offspring, offspring survival) in this plural breeding and
      communal rearing rodent. We found only a small effect of heterogeneity of food
      resources on group size; the effect food resource distribution on group territory
      size varied across years. Group size did not vary with spatial variation in group
      territory size and quality. Importantly, there was no covariation between group
      size and quality of an individual's territory (i.e., a measure of individual
      access to resources), or between this measure of territory quality and
      reproductive success, implying no resource-based benefits to social degus.
      Overall, our results were more consistent with fitness-neutral relationships
      among spatial heterogeneity of resources, sociality, and territory size. The
      resource-dispersion hypothesis, however, did not provide a complete explanation
      for degu socioecology. Se han propuesto distintas hipotesis para explicar como la
      heterogeneidad de los recursos afecta la vida en grupos, o sociabilidad. Esta
      puede surgir en situaciones donde individuos en grupos grandes se benefician al
      monopolizar el acceso a recursos (hipotesis de defensa de recursos). Por otra
      parte, la vida en grupos tambien puede ser el resultado neutro (en terminos de
      adecuacion) de individuos que comparten un territorio con recursos suficientes
      (hipotesis de dispersion de recursos). Aunque algunos estudios previos han
      validado la hipotesis de dispersion de recursos, estos solo han evaluado un
      numero limitado de las predicciones de esta hipotesis, lo que ha dificultado
      distinguir entre esta y otras hipotesis alternativas. Durante un estudio de 4
      anos cuantificamos los efectos de la heterogeneidad espacial de alimento y
      distribucion de refugios sobre el tamano de grupo y dos componentes del exito
      reproductivo (numero per capita de crias, supervivencia de las crias) en Octodon
      degus. Se registraron efectos relativamente pequenos de la heterogeneidad
      espacial del alimento sobre el tamano de grupo, y variables entre anos sobre el
      tamano del territorio de cada grupo. El tamano de grupo no fue afectado por la
      variacion espacial en el tamano y calidad del territorio de los grupos. No se
      registro co-variacion entre el tamano de los grupos y la calidad del territorio
      de cada individuo (una medida individual del acceso a recursos), o entre la
      calidad del territorio individual y el exito reproductivo, lo que sugiere
      ausencia de beneficios derivados del uso social de recursos en degus. En general,
      los resultados fueron mas consistentes con un escenario de efectos neutros de la
      heterogeneidad espacial de recursos sobre la sociabilidad. Sin embargo, la
      hipotesis de dispersion de recursos no explico el conjunto de efectos (o su
      ausencia) asociados a la socioecologia del degu.

PMID- 30302033
TI  - Proprietary Herbal Extract Downregulates the Gene Expression of IL-1alpha in
      HaCaT Cells: Possible Implications Against Nonscarring Alopecia.
AB  - Background: Currently while, topical minoxidil and oral finasteride are the only
      medications approved in androgenetic alopecia (AGA), the cause oriented treatment
      and immunsupressive treatment are being performed in telogen effluvium (TE) and
      alopecia areata (AA) respectively. Considering the inflammatory factors in the
      pathogenesis of these three nonscarring alopecia forms, we have formulated a
      mixture for topical usage composed of six different herbal extracts (HE) which
      have already known antiinflammatory and antioxidant features. Materials and
      Methods: In addition to performing the phytochemical analysis of HE, we detected
      the gene expression level of IL-1alpha, the crucial hair loss mediator, for the
      putative efficacy in nonscarring alopecia. Cell proliferation assay was performed
      by XTT reagent. After determination of non-cytotoxic concentration, HaCaT cells
      were treated with HE. RNA isolations were carried out from both non-treated and
      treated cell groups by using TRI-reagent. Gene expressions of IL-1alpha and as
      control GAPDH were determined by RT-qPCR analysis. Results: Results were
      represented as "IL-1alpha/GAPDH Fold Change". HE solution caused statistically
      significant downregulation of IL-1alpha gene expressions (p<0.0001), compared to
      untreated control cells. HE treatment ended up with 0.1900 fold change for IL
      1alpha. Conclusion: IL-1alpha is a direct growth inhibitory agent in hair
      follicles and an important actor in the pathogenesis of AGA , TE, and AA.
      Considering together the vitamins, flavonoids, and trace elements identified in
      the phytochemical analyses and downregulation of IL-1alpha in HaCaT cells, our HE
      may be an auxiliary agent in the therapy of these three nonscarring alopecia
      forms.

PMID- 30302034
TI  - Approach to bone procedure in fixed equinovarus deformity in cerebral palsy.
AB  - Fixed equinovarus deformity in cerebral palsy requires bone procedures for
      surgical correction. We reported the outcome of surgical procedure establishing
      the approach to multiple osteotomy and fusion to this problem. Retrospectively,
      55 feet were reviewed. Step of surgical evaluation were applied to all patients
      by addressing each component of equinovarus deformity. 31 feet achieved
      correction by multiple osteotomy. Overall 78% had good outcome and maintained
      plantigrade foot. This study had outlined a simple surgical step-approached
      procedure to address fixed equinovarus deformity in cerebral palsy with high
      success rates. We recommended multiple bone osteotomy to preserve joint motion.

PMID- 30302035
TI  - Update in Hepatic Encephalopathy.

PMID- 30302036
TI  - L-Ornithine L-Aspartate is Effective and Safe for the Treatment of Hepatic
      Encephalopathy in Cirrhosis.

PMID- 30302037
TI  - The New INASL President: Physician-Scientist par Excellence.

PMID- 30302038
TI  - A Placebo-Controlled, Multicenter, Double-Blind, Phase 2 Randomized Trial of the
      Pan-Caspase Inhibitor Emricasan in Patients with Acutely Decompensated Cirrhosis.
AB  - Background: Cirrhosis and acute-on-chronic liver failure (ACLF) are associated
      with systemic inflammation, and caspase-mediated hepatocyte cell death. Emricasan
      is a novel, pan-caspase inhibitor. Aims of this study were to assess the
      pharmacokinetics, pharmacodynamics, safety and clinical outcomes of emricasan in
      acute decompensation (AD) of cirrhosis. Methods: This was a phase 2, multicentre,
      double-blind, randomized trial. The primary objective was to evaluate the
      pharmacokinetics, pharmacodynamics and safety of emricasan in patients with
      cirrhosis presenting with AD and organ failure. AD was defined as an acute
      decompensating event <=6 weeks' duration. Patients were randomized
      proportionately to emricasan 5 mg bid, emricasan 25 mg bid, emricasan 50 mg bid
      or placebo. Treatment was continued to 28 days, or voluntary discontinuation.
      Results: Twenty-three subjects were randomized, of whom 21 were dosed (placebo n
      = 4; 5 mg n = 5; 25 mg n = 7; 50 mg n = 5). Pharmacokinetic data showed 5 mg dose
      was associated with low plasma levels (<50 ng/ml), and 25 mg and 50 mg doses
      showed comparable pharmacokinetic profiles. Therefore, for analysis of secondary
      endpoints, placebo and 5 mg groups were merged into a 'placebo/low-dose' group,
      and 25 mg and 50 mg groups were merged into a 'high-dose' group. Five deaths
      occurred amongst the 21 patients, all due to progression of liver disease (2 in
      placebo/low-dose, 3 in high-dose). No statistically significant changes from
      baseline MELD score or CLIF-C ACLF score were noted between placebo/low-dose and
      high-dose groups at day 7 (MELD -1 vs -1, CLIF-C ACLF 0.7 vs 0.8). An initial
      reduction in cleaved keratin M30 fragment was noted between placebo/low-dose and
      high-dose groups (percent relative change: day 2: -11.6 vs -42.6, P = 0.017, day
      4: -3.5 vs -38.9 P = 0.017) although this did not persist to day 7 (-3.1 vs 
      20.8, P = 0.342). Conclusion: This study demonstrates that emricasan is safe and
      well tolerated in advanced liver disease. However, this study fails to provide
      proof-of-concept support for caspase inhibition as a treatment strategy for ACLF.
      Trial registration: EudraCT 2012-004245-33.

PMID- 30302039
TI  - High Prevalence of Cirrhosis at Initial Presentation Among Safety-Net Adults with
      Chronic Hepatitis B Virus Infection.
AB  - Background and aims: Delays in diagnosis of chronic hepatitis B virus infection
      (HBV) may be more common among underserved safety-net populations, contributing
      to more advanced disease at presentation. We aim to evaluate rates of and
      predictors of cirrhosis and cirrhosis-related complications among adults with
      chronic HBV. Methods: We retrospectively evaluated consecutive chronic HBV adults
      from gastroenterology clinics from July 2014 to May 2016 at a community-based
      safety-net hospital. Prevalence of cirrhosis or cirrhosis-related complications
      (ascites, variceal bleeding, hepatic encephalopathy (HE), hepatocellular
      carcinoma (HCC)) at initial presentation was stratified by sex and
      race/ethnicity. Predictors of cirrhosis or cirrhosis-related complications at
      presentation were evaluated with multivariate logistic regression. Results: Among
      329 chronic HBV patients (mean age 49.1 years, 55.3% male, 66.5% Asian, 18.6%
      HBeAg positive) 27.7% had cirrhosis at presentation, 4.3% ascites, 3.7% variceal
      bleeding, 4.9% HE, and 4.0% HCC. Compared to women, men were more likely to have
      cirrhosis (34.6% vs. 19.1%, P < 0.01) and variceal bleeding (5.6% vs. 1.4%, P <
      0.05) at presentation. On multivariate regression, older age at presentation (OR,
      1.04; 95% CI, 1.01-1.07; P = 0.003) and positive HBeAg (OR, 2.57; 95% CI, 1.20
      5.51; P = 0.015) were associated with higher odds of cirrhosis at presentation,
      whereas men had a non-significant trend toward higher odds of cirrhosis (OR,
      1.88; 95% CI, 0.99-3.58; P = 0.055). Conclusion: Among adults with chronic HBV at
      an ethnically diverse safety-net hospital system, nearly 30% of patients had
      cirrhosis at initial presentation, with the greatest risk seen among patients of
      male sex, older age, and with positive HBeAg.

PMID- 30302040
TI  - Impact of Direct Acting Antiviral Drugs in Treatment Naive HCV Cirrhosis on
      Fibrosis and Severity of Liver Disease: A Real Life Experience from a Tertiary
      Care Center of North India.
AB  - Background/aims: Treatment of chronic hepatitis C infection with direct-acting
      antiviral (DAA) drugs has been highly effective, but data regarding benefit in
      advanced liver disease is relatively scarce in Indian patients. The aim of this
      study was to determine the effects of DAA in patients with HCV related cirrhosis
      (compensated/decompensated) who achieved sustained virological response post
      therapy at 12 weeks (SVR12). Methods: Sixty-three patients with HCV related
      cirrhosis treated with sofosbuvir based regimen were evaluated. Data regarding
      baseline demographics, the severity of liver disease and treatment regimen were
      collected. The primary end point was to evaluate the effect of treatment (SVR12)
      on the severity of liver disease with the secondary end point being to observe
      for any adverse events related to treatment. Results: Treatment naive patients
      with HCV cirrhosis either due to genotype 1 or genotype 3 were divided into two
      groups: group A (compensated cirrhosis), group B (decompensated cirrhosis). SVR12
      in group A was 91.66% (33/37) and in group, B was 73.17% (30/41). Baseline mean
      liver stiffness measurement (LSM) in group A was 16.81 +/- 3.57 kPa which
      decreased to 11.19 +/- 1.75 kPa at SVR12 (P-value <0.0001). Baseline mean APRI
      and FIB-4 score in group A were 1.228 +/- 0.499 and 2.61 +/- 1.06 and in group B
      were 2.156 +/- 1.10 and 5.71 +/- 2.06 respectively which decrease to 0.415 +/-
      0.115 and 1.25 +/- 0.46 in group A, to 0.759 +/- 0.275 and 2.60 +/- 1.12 in group
      B following SVR12 (P value <0.0001). Mean MELD-Na improved from baseline 9.93 +/-
      2.04, 20.70 +/- 4.52 to 7.21 +/- 0.92, 14.23 +/- 4.51 respectively in group A and
      B at SVR12 (P-value <0.0001). Child-Turcotte-Pugh score improved by 1 in 27.27%
      (9/33) and >=2 in 76.67% (23/30) of patients in group A and group B respectively.
      Conclusion: There was a significant improvement in severity of liver disease as
      depicted by the decrease in LSM and other noninvasive marker of fibrosis in
      patients who achieved SVR12 on DAA therapy.

PMID- 30302041
TI  - Evaluation of Splenic Stiffness in Patients of Extrahepatic Portal Vein
      Obstruction Using 2D Shear Wave Elastography: Comparison with Intra-Operative
      Portal Pressure.
AB  - Background/Aims: To compare splenic stiffness (SS) with intra-operative portal
      pressures (PPs) in patients of extrahepatic portal vein obstruction (EHPVO).
      Methods: Twenty-one patients (14 males; 7 females) of mean age 20.4 years with
      clinical and sonographic diagnosis of EHPVO were included in this approved
      prospective study. Endoscopy for esophageal varices (EV) was done in all patients
      followed by ultrasonographic 2D shear wave elastography (SWE) of spleen. Three
      values were taken at different areas of spleen avoiding major vessels and mean
      was calculated. Intra-operative PP was measured from an omental vein during
      proximal spleno-renal shunt surgery. The PP was compared and correlated with SS
      along with other parameters. Results: The mean SS was 46.04 +/- 8.0 kPa and the
      mean PP was 33.29 +/- 4.1 mmHg. There was no significant correlation between PP
      and SS (P = 0.61) and between grades of EV and SS (P = 0.38). Significant
      correlation was seen between grades of EV and PP (0.04). SS also did not show
      significant correlation with splenic size or duration of disease. Conclusion: SS
      measured by 2D SWE did not correlate with PP and thus may not help in predicting
      gastrointestinal bleed in patients of EHPVO.

PMID- 30302042
TI  - Race and Gradient Difference Are Associated with Increased Risk of Hepatic
      Encephalopathy Hospital Admission After Transjugular Intrahepatic Portosystemic
      Shunt Placement.
AB  - Background/Aims: Hepatic encephalopathy (HE) is a well-recognized complication of
      transjugular intrahepatic portosystemic shunt (TIPS) placement. The aim of this
      investigation was to evaluate incidence and predictors of post-TIPS HE
      necessitating hospital admission in a non-clinical trial setting. Methods: We
      performed a retrospective cohort study identifying 273 consecutive patients
      undergoing TIPS from 2010 to 2015 for any indication; 210 met inclusion/exclusion
      criteria. The primary endpoint was incidence of post-TIPS HE defined as
      encephalopathy with no other identifiable cause requiring hospitalization within
      90 days of TIPS. Clinical demographics and procedural variables were collected
      and analyzed to determine predictors of readmission for post-TIPS HE. Categorical
      variables were analyzed using Fisher's exact test; continuous variables were
      compared using Levene's t-test and student's t-test; P < 0.05, significant.
      Results: Forty-two of 210 patients (20%) developed post-TIPS HE requiring
      hospitalization within 90 days. On analysis of cohorts (post-TIPS HE vs. no post
      TIPS HE): non-white race (31.0% vs. 17.5%, P = 0.022) and increased hepatic
      venous pressure gradient (HVPG) difference during TIPS (10.5 vs. 8.9 mmHg, P =
      0.030) were associated with an increased incidence of HE requiring readmission
      within 90 days. Conclusions: HE remains a common complication of TIPS. Non
      Caucasian race is a significant clinical demographic associated with increased
      risk for readmission. Independent of initial or final HVPG, HVPG difference
      appears to be a significant modifiable technical risk factor. In the absence of
      clear preventative strategies for post-TIPS encephalopathy, non-Caucasians with
      HVPG reductions >9 mmHg may require targeted follow up evaluation to prevent
      hospital readmission.

PMID- 30302043
TI  - Pathogenesis of Hepatic Encephalopathy in Chronic Liver Disease.
AB  - Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that occurs
      during chronic liver disease (CLD). While ammonia and other precipitating factors
      in liver disease including inflammation, bile acids, oxidative stress, and
      lactate play a role in the pathogenesis of HE, the exact mechanism that leads to
      HE is not fully understood. Notably, accumulating evidence points toward a
      synergic effect rather than independent actions among precipitating factors that
      contributes to the development and severity of HE in CLD. Hence, this review is
      aimed to briefly discuss the single and synergic interplay of pathological
      factors in the progression and severity of HE.

PMID- 30302045
TI  - Role of Peripheral Inflammation in Hepatic Encephalopathy.
AB  - A growing body of evidence now highlights a key role for systemic inflammation in
      altering behavior and mood in patients with liver disease. How inflammation
      occurring in the periphery in the context of liver disease, communicates with the
      brain to mediate changes in neurotransmission and thereby behavior is
      incompletely understood. Traditional routes of communication between the
      periphery and the brain involve neural (i.e. vagal afferent nerves) and humoral
      (blood-borne) pathways, with increased circulating levels of endotoxin and
      cytokines (especially Tumor Necrosis Factor alpha, TNFalpha) that occur during
      systemic inflammatory responses, as being primarily implicated in mediating
      signaling via these pathways. However, in recent years communication via
      peripheral immune-cell-to-brain and the gut-microbiota-to-brain routes have
      received increasing attention in the context of liver disease for their ability
      to modulate brain function, and generate a spectrum of symptoms ranging from
      fatigue and altered mood to overt Hepatic Encephalopathy (HE). In this review, we
      discuss periphery-to-brain communication pathways and their potential role in
      mediating systemic inflammation-associated alterations in behavior, that are in
      turn ultimately part of a spectrum of brain changes linked to the development of
      clinically apparent HE.

PMID- 30302044
TI  - Hyperammonemia in Hepatic Encephalopathy.
AB  - The precise mechanism underlying the neurotoxicity of Hepatic Encephalopathy (HE)
      is remains unclear. The dominant view has been that gut-derived nitrogenous
      toxins are not extracted by the diseased liver and thereby enter the brain. Among
      the various toxins proposed, the case for ammonia is most compelling. Events that
      lead to increased levels of blood or brain ammonia have been shown to worsen HE,
      whereas reducing blood ammonia levels alleviates HE. Clinical, pathological, and
      biochemical changes observed in HE can be reproduced by increasing blood or brain
      ammonia levels in experimental animals, while exposure of cultured astrocytes to
      ammonium salts reproduces the morphological and biochemical findings observed in
      HE. However, factors other than ammonia have recently been proposed to be
      involved in the development of HE, including cytokines and other blood and brain
      immune factors. Moreover, recent studies have questioned the critical role of
      ammonia in the pathogenesis of HE since blood ammonia levels do not always
      correlate with the level/severity of encephalopathy. This review summarizes the
      vital role of ammonia in the pathogenesis of HE in humans, as well as in
      experimental models of acute and chronic liver failure. It further emphasizes
      recent advances in the molecular mechanisms involved in the progression of
      neurological complications that occur in acute and chronic liver failure.

PMID- 30302046
TI  - Cerebral Blood Flow and Metabolism in Hepatic Encephalopathy-A Meta-Analysis.
AB  - Hepatic Encephalopathy (HE) is associated with abnormalities in brain metabolism
      of glucose, oxygen and amino acids. In patients with acute liver failure,
      cortical lactate to pyruvate ratio is increased, which is indicative of a
      compromised cerebral oxidative metabolism. In this meta-analysis we have reviewed
      the published data on cerebral blood flow and metabolic rates from clinical
      studies of patients with HE. We found that hepatic encephalopathy was associated
      with reduced cerebral metabolic rate of oxygen, glucose, and blood flow. One
      exemption was in HE type B (shunt/by-pass) were a tendency towards increased
      cerebral blood flow was seen. We speculate that HE is associated with a disturbed
      metabolism-cytopathic hypoxia-and that type specific differences of brain
      metabolism is due to differences in pathogenesis of HE.

PMID- 30302048
TI  - Efficacy of l-Ornithine l-Aspartate for the Treatment of Hepatic Encephalopathy
      and Hyperammonemia in Cirrhosis: Systematic Review and Meta-Analysis of
      Randomized Controlled Trials.
AB  - Background/objectives: l-Ornithine l-Aspartate (LOLA) is a mixture of two
      endogenous amino acids with the capacity to fix ammonia in the form of urea
      and/or glutamine. Its' efficacy for the treatment of Hepatic Encephalopathy (HE),
      a known hyperammonemic disorder, remains the subject of debate. This study
      quantitatively analyzed the efficacy of LOLA in patients with cirrhosis and HE.
      Methods: Efficacy was defined as the extent of lowering of blood ammonia and
      improvement of mental state assessed in clinically overt HE (OHE) by Westhaven
      criteria or psychometric testing for assessment of Minimal HE (MHE). Appropriate
      keywords were used for electronic and/or manual searches of databases to identify
      RCTs for inclusion. Study quality and risk of bias were assessed using the Jadad
      Composite Scale together with The Cochrane Scoring Tool. Random Effects Models
      were used to express pooled Risk Ratio (RR) or Mean Difference (MD) with
      associated 95% Confidence Intervals (CI). Results: 10 RCTs (884 patients) were
      included. Regression analysis showed no evidence of publication bias or other
      small study effects. Eight RCTs had low risk of bias by Jadad/Cochrane criteria.
      Comparison with placebo/no intervention controls revealed that LOLA was
      significantly more effective for improvement of mental state in all types of HE
      (RR 1.36 (95% CI 1.10-1.69), p = 0.005), OHE (RR: 1.19, 95% CI of 1.01-1.39, test
      for overall effect: Z = 2.14, p = 0.03), MHE (RR: 2.15 (1.48-3.14), p < 0.0001)
      and for lowering of blood ammonia (MD: -17.50 MUmol/l (-27.73 to (-7.26)), p =
      0.0008). Improvement of mental state was greater in trials with low risk of bias.
      Heterogeneity was reduced in trials from Europe or with >100 participants. Oral
      LOLA appeared particularly effective for the treatment of MHE. Conclusion: LOLA
      appears to improve mental state and lower ammonia in patients with HE or MHE.
      Further studies are required in some subgroups of HE and in the era of HE
      reclassification.

PMID- 30302047
TI  - Hepatic Encephalopathy and Astrocyte Senescence.
AB  - Hepatic Encephalopathy (HE) is a severe complication of acute or chronic liver
      diseases with a broad spectrum of neurological symptoms including motor
      disturbances and cognitive impairment of different severity. Contrary to former
      beliefs, a growing number of studies suggest that cognitive impairment may not
      fully reverse after an acute episode of overt HE in patients with liver
      cirrhosis. The reasons for persistent cognitive impairment in HE are currently
      unknown but recent observations raise the possibility that astrocyte senescence
      may play a role here. Astrocyte senescence is closely related to oxidative stress
      and correlate with irreversible cognitive decline in aging and neurodegenerative
      diseases. In line with this, surrogate marker for oxidative stress and senescence
      were upregulated in ammonia-exposed cultured astrocytes and in post mortem brain
      tissue from patients with liver cirrhosis with but not without HE. Ammonia
      induced senescence in astrocytes involves glutamine synthesis-dependent formation
      of reactive oxygen species (ROS), p53 activation and upregulation of cell cycle
      inhibitory factors p21 and GADD45alpha. More recent studies also suggest a role
      of ROS-induced downregulation of Heme Oxygenase (HO)1-targeting micro RNAs and
      upregulation of HO1 for ammonia-induced proliferation inhibition in cultured
      astrocytes. Further studies are required to identify the precise sequence of
      events that lead to astrocyte senescence and to elucidate functional implications
      of senescence for cognitive performance in patients with liver cirrhosis and HE.

PMID- 30302049
TI  - De Novo Autoimmune Hepatitis After Living Donor Liver Transplantation: A Series
      of 4 Cases.
AB  - While Autoimmune Hepatitis (AIH) may recur in patients after liver transplant, an
      AIH like presentation (positive auto antibodies, raised immunoglobulin G, raised
      transaminases and histology showing plasma cell rich infiltrate) may also occur
      in liver transplant recipients who had transplant for some other disease, called
      De novo Autoimmune Hepatitis (DAIH). A timely diagnosis and treatment can prevent
      further graft dysfunction. We report 4 cases of DAIH after living donor liver
      transplantation.

PMID- 30302050
TI  - Percutaneous Transhepatic Approach for Recanalization of Superior Mesenteric and
      Portal Vein in a Patient With Pancreatic Neuroendocrine Tumor Presenting With
      Bleeding Duodenal Varices: A Brief Case Report.
AB  - Occlusion of Portal Vein (PV) and Superior Mesenteric Vein (SMV) is a known
      effect of local infiltration by pancreatic or mesenteric neuroendocrine tumors.
      Venous occlusion leads to formation of collateral pathways to restore hepatopetal
      flow in main PV and these collateral pathways can be seen in the form of ectopic
      (duodenal or jejunal) varices. We present a case of bleeding duodenal varices
      secondary to SMV occlusion by a locally infiltrating pancreatic neuroendocrine
      tumor which was successfully treated by coil embolization of varices and SMV
      stenting of the occluded venous segment after failure of endoscopic glue
      injection. Various endovascular minimally invasive approaches have been described
      in literature for recanalization of SMV in such clinical scenarios which maybe
      challenging to treat for surgical methods. We recommend use of the retrograde
      transhepatic technique for recanalization of occluded SMV and embolization of
      associated varices as an alternate treatment option in such scenarios.

PMID- 30302051
TI  - Primary Hepatic Leiomyosarcoma: Histopathologist's Perspective of a Rare Case.
AB  - Primary hepatic leiomyosarcoma is a rare primary mesenchymal tumor of the liver
      requiring exclusion of any other primary site of origin and histological and
      immunohistochemical exclusion of other hepatic/extrahepatic tumors with spindle
      cell morphology. Only about 70 cases are reported in the English literature and
      many of these tumors have predisposing conditions in the form of
      immunosuppression or associated malignancies. The occurrence of this tumor in the
      immunocompetent individual is also known. Histomorphology of this tumor shows a
      spindle cell lesion which needs to be distinguished from other spindle cell
      lesions of this region. The main diagnostic challenge of this tumor lies in its
      rarity, lack of awareness and morphological mimickers in the given site. A
      complete range of immunohistochemical markers is required to distinguish the
      lesion from its close morphological mimickers. Here, we discuss a case of primary
      hepatic leiomyosarcoma in an adult female patient with detailed
      histomorphological differentials and respective immunoprofiles.

PMID- 30302052
TI  - Hepatic Dysfunction in a Child Post Bone Marrow Transplantation.
AB  - A 10-year-old female child, a known case of Beta-Thalassemia major with
      superimposed chronic Hepatitis C Viral (HCV) infection, underwent bone marrow
      transplantation and presented, 7 months later, with worsening hepatic functions
      and skin rash. Considering the wide variety of possible etiologies, she was
      evaluated and later confirmed as a case of hepatic dysfunction secondary to HCV
      related hepatic injury with concomitant chronic graft versus host disease
      (dermatological involvement only).

PMID- 30302053
TI  - Monte Carlo Simulations Demonstrate Algorithmic Interventions Over Time Reduce
      Hospitalisation in Patients With Schizophrenia and Bipolar Disorder.
AB  - Non-adherence with pharmacologic treatment is associated with increased rates of
      relapse and rehospitalisation among patients with schizophrenia and bipolar
      disorder. To improve treatment response, remission, and recovery, research
      efforts are still needed to elucidate how to effectively map patient's response
      to medication treatment including both therapeutic and adverse effects,
      compliance, and satisfaction in the prodromal phase of illness (ie, the time
      period in between direct clinical consultation and relapse). The Actionable
      Intime Insights (AI2) application draws information from Australian Medicare
      administrative claims records in real time when compliance with treatment does
      not meet best practice guidelines for managing chronic severe mental illness.
      Subsequently, the AI2 application alerts clinicians and patients when patients do
      not adhere to guidelines for treatment. The aim of this study was to evaluate the
      impact of the AI2 application on the risk of hospitalisation among simulated
      patients with schizophrenia and bipolar disorder. Monte Carlo simulation
      methodology was used to estimate the impact of the AI2 intervention on the
      probability of hospitalisation over a 2-year period. Results indicated that when
      the AI2 algorithmic intervention had an efficacy level of (>0.6), over 80% of
      actioned alerts were contributing to reduced hospitalisation risk among the
      simulated patients. Such findings indicate the potential utility of the AI2
      application should replication studies validate its methodologic and ecological
      rigour in real-world settings.

PMID- 30302054
TI  - Ammonia-Oxidizing Archaea (AOA) Play with Ammonia-Oxidizing Bacteria (AOB) in
      Nitrogen Removal from Wastewater.
AB  - An increase in the number of publications in recent years indicates that besides
      ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea (AOA) may play an
      important role in nitrogen removal from wastewater, gaining wide attention in the
      wastewater engineering field. This paper reviews the current knowledge on AOA and
      AOB involved in wastewater treatment systems and summarises the environmental
      factors affecting AOA and AOB. Current findings reveal that AOA have stronger
      environmental adaptability compared with AOB under extreme environmental
      conditions (such as low temperature and low oxygen level). However, there is
      still little information on the cooperation and competition relationship between
      AOA and AOB, and other microbes related to nitrogen removal, which needs further
      exploration. Furthermore, future studies are proposed to develop novel nitrogen
      removal processes dominated by AOA by parameter optimization.

PMID- 30302055
TI  - Primary cutaneous nocardiosis: a diagnosis of consideration in a renal transplant
      recipient.
AB  - Background: The cutaneous nocardiosis remains a diagnostic challenge: similar
      clinical presentations as of cutaneous diseases with different etiology-and the
      inherent difficulty in cultivating the pathogen. Case presentation: Herein, we
      describe a case of primary cutaneous nocardiosis in a renal transplant recipient;
      treated with anti-tubercular drugs due to misdiagnosis of cutaneous tuberculosis.
      On clinical examinations, a few red erythematous papules with erosions and
      crusting seen, over prior surgery scar of renal transplant. Multiple basophilic
      colonies surrounded by neutrophilic abscesses and granulation tissue were seen on
      histopathological examinations. The presumptive identification was done by Ziehl
      neelson staining, bacterial culture, biochemical interpretations, and
      susceptibility pattern of the isolates to antibiotics. Radiographic imaging of
      brain and lungs were normal; no feature of disseminated nocardiosis seen. After 3
      months of an anti-microbial therapy i.e. TMP-SMX(sulfamethoxazole and
      trimethoprim); the patient underwent progressive changes no relapse noted;
      transplant function observed in a good state, found asymptomatic with limited
      side effects on a regular follow up till now. Conclusion: Cutaneous nocardiosis
      can occur in the renal-transplant patient. Therefore, a high degree of clinical
      suspicions, extensive clinical differentiation, early detection of the pathogen,
      apt selection of the antimicrobial therapy, correct dosing, and treatment
      duration is crucial for successful outcomes.

PMID- 30302056
TI  - Quality of nursing work life and turnover intention among nurses of tertiary care
      hospitals in Riyadh: a cross-sectional survey.
AB  - Background: Nurse turnover has a negative impact on the ability to meet patient
      needs and provide a high quality of care, which may create more stress on other
      staff due to increased workloads. This can lead to critical changes in the
      behavior of nurses towards their jobs resulting in low work satisfaction, low
      productivity, and leaving the organization. Thus, this study aimed to assess the
      quality of nursing work life (QNWL), to explore the nurses' turnover intention
      and to examine the correlation between QNWL and nurses' turnover intention.
      Methods: A cross-sectional survey was conducted on nurses with at least 1 year of
      nursing experience at two hospitals selected randomly from Riyadh, Saudi Arabia:
      King Fahad Medical City and King Faisal Specialized Hospitals. Data were
      collected using a self-administered questionnaire comprising four sections
      (Brooks' survey of QNWL, Anticipated Turnover Scale (ATS), open-ended questions
      and demographic characteristics). Results: A sample of 364 nurses was recruited.
      Results proposed that the participants were dissatisfied with their work life
      (54.7%), with almost 94% indicating a turnover intention from their current
      hospital. Moreover, 154 (93.3%) out of 165 nurses who reported satisfaction with
      QNWL indicated the intention to turnover. The correlation between QNWL and ATS
      for binary variables was too week (r = - 0.024) and statistically not significant
      (p = 0.206). Conclusion: The QNWL and nurse turnover are challenging issues for
      healthcare organizations because of its consequences and impact on patient care.
      Our study provided critical findings low indication satisfaction of nurses with
      their QNWL and a high turnover intention. The results of this study could be used
      as a nexus for the development of regulations and practical strategies to enhance
      QNWL and to decrease the turnover.

PMID- 30302057
TI  - Conserved cell populations in doxorubicin-resistant human nasal natural killer/T
      cell lymphoma cell line: super multidrug resistant cells?
AB  - Background: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is a distinct
      clinicopathological entity and EBV-associated disease that is highly aggressive.
      Many patients had failed to respond to conventional chemotherapy or relapsed
      after treatment. Multi-drug resistance is a major cause that leads to these
      desperate failures. However, the specific mechanism of drug resistance is still
      unclear. Methods: In the previous study, we firstly developed a doxorubicin
      resistant ENKL cell line known as SNK-6/ADM, and then a small quantity of side
      population (SP) cells were derived from SNK-6/ADM and named SNK-6/ADM-SP. In
      order to explore the biological characteristics and mechanism of drug-resistance
      of these cells, SNK-6, SNK-6/ADM and SNK-6/ADM-SP cells were utilized to evaluate
      potentially differences of chemotherapy resistance index (RI), morphology,
      proliferation, cell cycles, expression of ATP-binding cassette (ABC) transporters
      (ABCG1, ABCG2 and ABCC4) and surface markers, cytokine sensitivity, and situation
      of EBV infection. Results: We identified SNK-6/ADM-SP is a specific multidrug
      resistant cell population with a higher level of RI than SNK-6/ADM. Relevant
      evaluations showed that SNK-6/ADM-SP presented a series of conserved biological
      behaviors including relatively poor proliferation ability, high expression of
      ABCG2, weak sensitivity to IL-15 which could stimulate normal ENKL cells'
      proliferation and differentiation, and EBV inhibition with low level of EBV-DNA
      replication and EBV-antigen expression. Conclusions: This discovered cellular
      heterogeneity of ENKL could provide a new perspective to better understand the
      mechanisms of drug resistance and overcome elusive response to chemotherapy of
      ENKL.

PMID- 30302059
TI  - New ACG Guideline for the Management of Crohn's Disease.

PMID- 30302058
TI  - Overexpression of LASS2 inhibits proliferation and causes G0/G1 cell cycle arrest
      in papillary thyroid cancer.
AB  - Background: The aim of this study was to investigate the role of LAG1 longevity
      assurance homologue 2 (LASS2) in papillary thyroid cancer (PTC). Methods:
      Immunohistochemistry staining was conducted to explore the expression levels of
      LASS2 in PTC tissues and adjacent normal thyroid tissues and nodular goiter
      tissues. Western blotting and RT-qPCR were performed to explore the expression
      levels of LASS2 in three PTC cell lines (TPC-1, K1, BCPAP). An Adv-LASS2-GFP
      recombinant adenovirus vector was constructed and transduced into BCPAP cells.
      Then CCK-8 assay, colony formation assay, cell cycle distribution, and apoptosis
      were performed. Western blotting was used to examine the expression of p21,
      cyclin D1, cyclin-dependent kinase 4, p53 and p-p53. Results: LASS2 was
      downregulated in PTC tissues compared with adjacent thyroid tissues or nodular
      goiter tissues. In addition, the expression of LASS2 was found to be associated
      with TNM stage and lymph node metastasis. BCPAP cells expressed the lowest LASS2
      compared to TPC-1 cells or K1 cells. Overexpression of LASS2 significantly
      inhibited proliferation, promoted apoptosis and caused G0/G1 cell cycle arrest in
      BCPAP cells. Furthermore, overexpression of LASS2 significantly increased the
      expression of p21, inhibited the expression of cyclin D1 and cyclin-dependent
      kinase 4, and increased the expression of p-p53, but did not effect the
      expression of p53 in BCPAP cells. Conclusion: Our findings indicate that
      overexpression of LASS2 inhibits PTC cell proliferation, promotes apoptosis and
      causes G0/G1 cell cycle arrest via a p53-dependent pathway. Thus, LASS2 may serve
      as a novel biomarker in PTC.

PMID- 30302060
TI  - Economic Comparison of Serologic and Molecular Screening Strategies for Hepatitis
      C Virus.
AB  - Background: Hepatitis C virus (HCV) screening is traditionally performed using an
      enzyme-linked immunosorbent assay (ELISA), and HCV infection is confirmed by
      measuring the viral load using polymerase chain reaction (PCR). An alternative
      screening approach is to use only PCR, without the ELISA pretest. Methods: We
      compared the cost ratio of screening for HCV using 2 approaches: (1) ELISA
      followed by PCR testing, and (2) PCR testing alone. The results were analyzed
      using a decision analysis model. A sensitivity analysis and a threshold analysis
      were performed by varying both the prevalence of HCV infection (to encompass
      populations in which viral infection is overrepresented) as well as the costs of
      PCR testing. Results: Under baseline assumptions, the costs of PCR testing alone
      were substantially greater than the combination of ELISA and PCR testing. The
      cost per patient screened using combination testing was $42.30, whereas testing
      with only PCR cost $200.00 per patient. The prevalence of HCV had a greater
      impact on the cost ratio than did the costs of laboratory tests. The use of PCR
      testing alone became less costly only when the prevalence of HCV infection was
      greater than 69.5%. Otherwise, the costs of the 2 approaches were similar when
      the cost of PCR was 1% of that of ELISA. Conclusion: From a pharmacoeconomic
      basis, the current approach of HCV screening (ie, using ELISA and PCR testing)
      was found to be the less expensive screening strategy in a general US population
      and for most cohorts in which HCV infection was noted to be overrepresented.
      Screening for HCV is less costly using solely PCR testing only when the
      prevalence of HCV infection is greater than 69.5%.

PMID- 30302061
TI  - The Role of Allergy Testing in Eosinophilic Esophagitis.
AB  - Eosinophilic esophagitis (EoE) is defined as a chronic, immune/antigen-mediated
      esophageal disease that can lead to symptoms of esophageal dysfunction. This
      disease is seen in both children and adults. Approximately 70% of patients with
      EoE have food antigen sensitization or other atopic conditions, suggesting an
      allergic etiology in the pathogenesis of the disease. The role of allergy testing
      to identify foods that lead to EoE is unclear. Three types of allergy tests
      currently exist: skin prick testing, atopy patch testing, and immunoassays for
      serum food-specific immunoglobulin E. It is important for gastroenterologists to
      work in conjunction with allergist colleagues in the care of patients with EoE,
      particularly in the management of comorbid atopic conditions.

PMID- 30302063
TI  - Highlights From the New ACG Guideline on Crohn's Disease Management.

PMID- 30302062
TI  - Perianal Fistulas in Patients With Crohn's Disease, Part 1: Current Medical
      Management.
AB  - Despite significant advances in the treatment of luminal inflammatory bowel
      disease, the treatment of perianal fistulas remains a clinical challenge.
      Perianal fistulas are traditionally described using the Parks classification
      based on their relationship to the external and internal anal sphincters.
      Traditional therapy for perianal fistulas focuses on antibiotics such as
      metronidazole or ciprofloxacin. However, medical management has expanded over the
      years to include immunomodulators and, most recently, biologic agents. Newer
      techniques such as intrafistulous biologic injections are also being explored as
      potentially effective treatments for patients with fistulizing disease. Here, in
      the first of a 2-part series on perianal fistulas in patients with Crohn's
      disease, we discuss the anatomy and classification of perianal fistulas as well
      as current medical therapies, including antibiotics, immunomodulators, biologic
      agents, and novel therapeutic agents. The second part of the series will focus on
      the surgical modalities that are available for patients with perianal fistulas in
      addition to novel endoscopic techniques and future therapies that are being
      investigated for the treatment of fistulizing Crohn's disease.

PMID- 30302064
TI  - The Use of Statins in Patients With Cirrhosis.

PMID- 30302065
TI  - Radiofrequency Ablation for the Treatment of Barrett Esophagus With Low-Grade
      Dysplasia.

PMID- 30302067
TI  - GASTRO-HEP News.

PMID- 30302066
TI  - Hemorrhoidal Banding and Anesthesia Partnerships as Ancillary Services to
      Gastroenterology Practices.

PMID- 30302068
TI  - Complete Technical Scheme for Automatic Biological Dose Estimation Platform.
AB  - To establish a complete technical solution for the automatic radiation biological
      dose estimation platform for biological dose estimation and classification of the
      wounded in large-scale radiation accidents, the "dose-effect curve by dicentric
      chromosome (DIC) automatic analysis" was established and its accuracy was
      verified. The effects of analyzed cell number and the special treatment of the
      culture on dose estimation by DIC automatic analysis were studied. Besides,
      sample processing capabilities of the special equipments were tested. The fitted
      "dose-effect curve by DIC automatic analysis" was presented as follows: Y =
      (0.01806 +/- 0.00032) D 2 + (0.01279 +/- 0.00084) D + (0.0004891 +/- 0.0001358)
      (R 2 = 0.961). Three-gradient scanning method, culture refrigeration method, and
      interprofessional collaboration under extreme conditions were proposed to improve
      the detection speed, prolong the sample processing time window, and reduce the
      equipment investment. In addition, the optimized device allocation ratio for the
      automatic biological dose estimation laboratory was proposed to eliminate the
      efficiency bottleneck. The complete set of technical solutions for the high
      throughput automatic biological dose estimation laboratory proposed in this study
      can meet the requirements of early classification and rapid biological dose
      assessment of the wounded during the large-scale nuclear radiation events, and it
      is worthy of further promotion.

PMID- 30302069
TI  - Quantitative Risk Assessment in the 1970s: A Personal Remembrance.

PMID- 30302071
TI  - Introduction The Second FESCC Continuous Postgraduate Course in Clinical
      Chemistry: New Trends in Classification and Management of Cardiovascular Disease.

PMID- 30302070
TI  - Temporary CBD Stenting with a Nelaton Tube Is a More Practical and Safer Option
      Than T-Tube Drainage after Conventional CBD Exploration for Choledocholithiasis.
AB  - Objective: We are trying to investigate the possibility, safety, and benefits of
      replacing the role of T-tube by another more safe and effective procedure for
      biliary decompression in the case of common bile duct (CBD) exploration. Methods:
      Our present study includes fifty consecutive patients who underwent a traditional
      CBD exploration due to choledocholithiasis. Patients were divided into 2 equal
      groups. In the 1st group, a spontaneously expelled Nelaton tube is placed in the
      CBD to aid in bile drainage to the duodenum, while in the 2nd group, a
      conventional T-tube is placed to decompress the CBD in the early postoperative
      (PO) days to a drainage bag. Operative and PO data as well as PO hospital stay
      time were recorded. All data were collected and statistically analyzed. Results:
      The mean operative time and PO hospital stay days were significantly low (p value
      < 0.05) in the Nelaton tube drainage group compared with the T-tube drainage
      group. On the other hand, the mean time needed for the abdominal drain removal
      was significantly higher in the T-tube drainage group (p value < 0.05).
      Conclusion: Nelaton tube with internal biliary drainage is effective and safer
      than T-tube drainage and it helps in reduction of the PO hospital stay time. In
      addition, it avoids all short-term complications of T-tube.

PMID- 30302072
TI  - Pathophysiology and Classification of Cardiovascular Diseases Caused by
      Atherosclerosis.

PMID- 30302073
TI  - Atherothrombosis: Pathogenesis of Cardiovascular Disease.

PMID- 30302074
TI  - Role of Inflammation in the Pathogenesis of Acute Coronary Syndromes.

PMID- 30302075
TI  - Genetics of Cardiovascular Disease.

PMID- 30302076
TI  - The Role of Lipids in the Development of Atherosclerosis and Coronary Heart
      Disease: Guidelines for Diagnosis and Treatment.

PMID- 30302077
TI  - Evaluation of Risk Markers for Acute Myocardial Infarction and Heart Failure:
      Present and the Future.

PMID- 30302078
TI  - Hypertension and Coronary Heart Disease.

PMID- 30302079
TI  - Diabetes Mellitus and Cardiovascular Disease.

PMID- 30302080
TI  - The Role of Pharmacogenetics in Management of Cardiovascular Disease.

PMID- 30302081
TI  - Natriuretic Peptides in Assessment of Ventricular Dysfunction.

PMID- 30302082
TI  - Treatment of Lipid Disorders in Cardiovascular Patients.

PMID- 30302083
TI  - Rational Diagnosis of Cardiovascular Disease.

PMID- 30302084
TI  - Recommendations on Use of Biochemical Markers in Acute Coronary Syndrome: IFCC
      Proposals.

PMID- 30302085
TI  - Strategy of Prevention of Cardiovascular Disease.

PMID- 30302086
TI  - Use of fungal alpha amylase and ascorbic acid in the optimisation of grain
      amaranth-wheat flour blended bread.
AB  - Grain amaranth-wheat flour bread was optimised using ascorbic acid (0.03% dry
      weight basis) and fungal alpha-amylase (10 ppm) to investigate their effects on
      sensory properties of the breads. Six formulations were used in the ratios of
      5:95, 10:90, 15:85, 20:80 and 25:75 grain amaranth to wheat flour compositions,
      while the control bread had 100% wheat flour. Consumer acceptability and
      preference ranking tests were conducted to describe and evaluate preference and
      acceptability of the breads. Analysis of consumer acceptability data revealed
      that there were significant differences (p < 0.05) for all the samples in all the
      attributes tested. Overall consumer acceptability results showed no difference at
      25% for all improvers. Principal component analysis for descriptive tests
      performed by a trained panel demonstrated variations among the breads in
      graininess, elasticity, crumb colour, stickiness and crumb moistness regardless
      of the improvers used. The study concludes that using improvers to optimise grain
      amaranth-wheat flour bread can help improve both the nutritional and organoleptic
      properties of bread.

PMID- 30302087
TI  - Rice bran triterpenoids improve postprandial hyperglycemia in healthy male
      adults: a randomized, double-blind, placebo-controlled study.
AB  - Background: Compared to white rice, brown rice induces a lower glycemic response
      in healthy and diabetic humans. This effect is partly attributed to the higher
      amounts of water- or oil-soluble bran components and dietary fiber in brown rice.
      We hypothesized that dietary supplementation with oil-soluble rice bran
      triterpenoids (RBTs; triterpene alcohol and sterol prepared from rice bran) might
      reduce the incidence of postprandial hyperglycemia in healthy humans. Objective:
      We examined the acute effects of a single RBT-supplemented meal on the
      postprandial blood glucose responses of healthy male adults in a double-blind,
      randomized, placebo-controlled, crossover trial. Design: Nineteen subjects
      consumed a test meal containing either placebo- or RBT-supplemented olive oil.
      Blood biomarkers were evaluated in a fasting state and up to 240 min
      postprandially. Results: Compared to the placebo-supplemented meal, the RBT
      supplemented meal significantly suppressed the increase in postprandial blood
      glucose level. A subclass analysis revealed that RBT-supplemented oil
      significantly reduced blood glucose increases in subjects with higher
      postprandial blood glucose elevations. Postprandial increases in blood insulin,
      glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptide-1 (GLP
      1) levels did not differ between the groups. Conclusion: These results suggest
      that RBT consumption improves postprandial hyperglycemia in healthy humans,
      especially those with higher postprandial glucose increases.

PMID- 30302088
TI  - Prediction of the Risk of Laparoscopy-Assisted Gastrectomy by Comparing Visceral
      Fat Area and Body Mass Index.
AB  - Propose: The purpose of this study was to compare the accuracy of visceral fat
      area (VFA) and body mass index (BMI) in predicting the risk of laparoscopic
      assisted gastrectomy. Methods: Clinicopathological and imaging data of 133
      patients who underwent laparoscopy-assisted gastrectomy were recorded, including
      17 cases of conversion to open surgery. The remaining 116 patients were
      retrospectively analyzed after we excluded 17 patients who had been transferred
      to laparotomy. The patients were divided into two groups according to BMI (<=25
      kg/m2: BMI-L group; >25 kg/m2: BMI-H group) and VFA (<=100 cm2: VFA-L group; >100
      cm2: VFA-H group). Clinical outcomes were compared between the BMI and VFA
      subgroups. Results: There were no differences in intraoperative blood loss and
      the number of harvested lymph nodes between low and high patients defined by BMI
      and VFA (p > 0.050). However, in the comparison of patients who underwent
      laparoscopic resection only, it was found that the operation time and
      intraoperative blood loss of the VFA-H group were more than those of the VFA-L
      group (p < 0.050). Compared to the VFA-L group, the VFA-H group had later first
      exhaust time (p = 0.018), more complications (p < 0.001), and longer hospital
      stays (p = 0.049). However, no similar conclusion was obtained in the BMI group
      (p > 0.050). Conclusion: This study demonstrates that VFA better evaluates the
      difficulty of laparoscopy-assisted gastrectomy and the risk of postoperative
      complications than BMI.

PMID- 30302089
TI  - Staffing at Ambulatory Endoscopy Centers in the United States: Practice, Trends,
      and Rationale.
AB  - Background: Endoscopy nurse (RN) has a pivotal role in administration and
      monitoring of moderate sedation during endoscopic procedures. When sedation for
      the procedure is administered and monitored by an anesthesia specialist, the role
      of an RN is less clear. The guidelines on this issue by nursing and
      gastroenterology societies are contradictory. Methods: Survey study of endoscopy
      lab managers and directors at outpatient endoscopy units in Texas. The questions
      related to staffing patterns for outpatient endoscopies and responsibilities of
      different personnel assisting with endoscopies. Results: Responses were received
      from 65 endoscopy units (response rate 38%). 63/65 (97%) performed at least a few
      cases with an anesthesia specialist. Of these, 49/63 (78%) involved only an
      endoscopy technician, without an additional RN in the room. At 12/49 (25%) units,
      the RN performed tasks of an endoscopy technician. At 14/63 (22%), an additional
      RN was present during endoscopic procedures and performed tasks not directly
      related to patient care. Conclusions: Many ambulatory endoscopy units do not have
      an RN present at all times when sedation is administered by an anesthesia
      specialist. An RN, when present, did not perform tasks commensurate with the
      education and training. This has implications about optimal utilization of nurses
      and cost of performing endoscopies.

PMID- 30302091
TI  - Development and Validation of an HPLC-MS/MS Method for Rapid Simultaneous
      Determination of Cefprozil Diastereomers in Human Plasma.
AB  - Background: Both cis- and trans-cefprozil have antimicrobial activity, but their
      potencies are quite different. It is therefore necessary to develop a sensitive
      method to simultaneously determine both isomers for pharmacokinetic and
      bioequivalence studies. Methods: An LC-MS/MS method, using stable isotope-labeled
      cefprozil as the internal standard, was developed and validated. The analytes
      were extracted from plasma by protein precipitation and separated on a reverse
      phase C18 column using a gradient program consisting of 0.5% formic acid and
      acetonitrile within 4 min. The mass spectrometry acquisition was performed with
      multiple reaction monitoring in positive ion mode using the respective [M+H]+
      ions, m/z 391.2->114.0 for cefprozil and 395.0->114.5 for cefprozil-D4. Results:
      The calibration curves were linear over the ranges of 0.025-15 MUg/mL for cis
      cefprozil and 0.014-1.67 MUg/mL for trans-cefprozil. The accuracies for the cis
      and trans isomers of cefprozil were 93.1% and 103.0%, respectively. The intra-
      and interassay precisions for the QC samples of the isomers were < 14.3%. The
      intra- and interassay precisions at the LLOQ were < 16.5%. Conclusions: The
      method was sensitive and reproducible and was applied in a pilot pharmacokinetic
      study of healthy volunteers.

PMID- 30302090
TI  - Serum Matrix Metalloproteinase 9 and Macrophage Migration Inhibitory Factor (MIF)
      Are Increased in Young Healthy Nonobese Subjects with Positive Family History of
      Type 2 Diabetes.
AB  - Insulin resistance increases the risk for cardiovascular disease (CVD) even in
      the absence of classic risk factors, such as hyperglycemia, hypertension,
      dyslipidemia, and obesity. Low-grade chronic inflammatory state is associated
      both with insulin resistance and atherosclerosis. An increased circulating level
      of proinflammatory proatherogenic factors and biomarkers of endothelial
      activation was observed in diabetes and CVD. The aim of our study was to assess
      serum proatherogenic and proinflammatory factors in young healthy nonobese
      subjects with positive family history of type 2 diabetes. We studied 74 young
      healthy nonobese subjects with normal glucose tolerance (age < 35 years, BMI < 30
      kg/m2), 29 with positive family history of type 2 diabetes (relatives, 25 males
      and 4 females) and 45 subjects without family history of diabetes (control group,
      39 males and 6 females). Hyperinsulinemic-euglycemic clamp was performed, and
      serum concentrations of monocyte chemoattractant protein-1 (MCP-1), interleukin
      18 (IL-18), macrophage inhibitory cytokine 1 (MIC-1), macrophage migration
      inhibitory factor (MIF), matrix metalloproteinase (MMP-9), and soluble forms of
      adhesion molecules were measured. Relatives had markedly lower insulin
      sensitivity (p = 0.019) and higher serum MMP-9 (p < 0.001) and MIF (p = 0.006),
      but not other chemokines and biomarkers of endothelial function. Insulin
      sensitivity correlated negatively with serum MMP-9 (r = -0.23, p = 0.045). Our
      data show that young healthy subjects with positive family history of type 2
      diabetes already demonstrate an increase in some nonclassical cardiovascular risk
      factors.

PMID- 30302092
TI  - Metabolic Engineered Biocatalyst: A Solution for PLA Based Problems.
AB  - Polylactic acid (PLA) is a biodegradable thermoplastic polyester. In 2010, PLA
      became the second highest consumed bioplastic in the world due to its wide
      application. Conventionally, PLA is produced by direct condensation of lactic
      acid monomer and ring opening polymerization of lactide, resulting in lower
      molecular weight and lesser strength of polymer. Furthermore, conventional
      methods of PLA production require a catalyst which makes it inappropriate for
      biomedical applications. Newer method utilizes metabolic engineering of
      microorganism for direct production of PLA through fermentation which produces
      good quality and high molecular weight and yield as compared to conventional
      methods. PLA is used as decomposing packaging material, sheet casting, medical
      implants in the form of screw, plate, and rod pin, etc. The main focus of the
      review is to highlight the synthesis of PLA by various polymerization methods
      that mainly include metabolic engineering fermentation as well as salient
      biomedical applications of PLA.

PMID- 30302093
TI  - A Very Rare Complication of Hepatitis A Infection: Acute Myocarditis-A Case
      Report with Literature Review.
AB  - Hepatitis A is a common viral infection with a benign course but in rare cases
      can progress to acute liver failure. It usually presents with abdominal pain,
      nausea, vomiting, diarrhea, jaundice, anorexia, or asymptomatically, but it can
      also present atypically with relapsing hepatitis and prolonged cholestasis. In
      addition, extrahepatic manifestations have been reported, including urticarial
      and maculopapular rash, acute kidney injury, autoimmune hemolytic anemia,
      aplastic anemia, acute pancreatitis, mononeuritis, reactive arthritis,
      glomerulonephritis, cryoglobulinemia, Guillain-Barre syndrome, and pleural or
      pericardial effusion. A rare manifestation of hepatitis A is acute myocarditis.
      We report a case of a young woman who presented with "flu-like symptoms" and was
      found to have severe elevation of liver enzymes due to acute hepatitis A
      infection. On her 3rd day of admission, the patient developed chest pain and
      nonspecific electrocardiographic changes. Her troponins rose to 16.4  ng/mL, and
      a transthoracic echocardiogram revealed global hypokinesis and a depressed
      ejection fraction at 30%. A CT angiography showed no evidence of significant
      coronary artery disease. The patient was managed supportively, and symptoms and
      laboratory findings slowly improved over the next 7 days. Her chest pain resolved
      and a follow-up echocardiogram showed improved ejection fraction to 45%.

PMID- 30302095
TI  - When the situation almost cannot be worse....

PMID- 30302094
TI  - Molecular Mechanisms of Transdifferentiation of Adipose-Derived Stem Cells into
      Neural Cells: Current Status and Perspectives.
AB  - Neurological diseases can severely compromise both physical and psychological
      health. Recently, adult mesenchymal stem cell- (MSC-) based cell transplantation
      has become a potential therapeutic strategy. However, most studies related to the
      transdifferentiation of MSCs into neural cells have had disappointing outcomes.
      Better understanding of the mechanisms underlying MSC transdifferentiation is
      necessary to make adult stem cells more applicable to treating neurological
      diseases. Several studies have focused on adipose-derived stromal/stem cell
      (ADSC) transdifferentiation. The purpose of this review is to outline the
      molecular characterization of ADSCs, to describe the methods for inducing ADSC
      transdifferentiation, and to examine factors influencing transdifferentiation,
      including transcription factors, epigenetics, and signaling pathways. Exploring
      and understanding the mechanisms are a precondition for developing and applying
      novel cell therapies.

PMID- 30302096
TI  - Dying from takotsubo syndrome at a young age: the crucial role of brain-heart
      interactions.

PMID- 30302097
TI  - Prediction of cognitive dysfunction after resuscitation - a systematic review.
AB  - Cardiac arrest (CA) due to cardiovascular disease is the leading cause of death
      in developed countries. It is estimated that over 350,000 people in Europe suffer
      from out-of-hospital cardiac arrest. According to the literature, the longer the
      episode of cardiac arrest, the greater the risk of cognitive impairment,
      especially short-term memory, as well as immediate and delayed recall. Other
      common dysfunctions include attention deficits and executive function disorders.
      The aim of this systematic review was to summarize current research on cognitive
      impairment in patients after sudden cardiac arrest. The electronic databases
      PubMed/MEDLINE, OVID, Web of Science, and EBSCO were searched using the following
      key words: 'sudden cardiac arrest', 'out-of-hospital cardiac arrest', 'cognitive
      function', 'cognitive impairment', 'functional outcome', 'cardiopulmonary
      resuscitation'. The most recent studies from the last 7 years (2011-2018) were
      included. Cognitive disorders occurred in a broad range of cases: from 13% to
      even 100%. In one study, cognitive deficits did not occur at all. Amongst the
      reviewed articles only two studies were carried out on a large group of patients.
      The remaining studies were conducted on a small group of respondents; therefore
      there was no possibility to generalize the results to the entire population. The
      areas in which the most cognitive impairment occurred were memory, executive
      functions and visual-motor skills. One of the conclusions derived from the
      reviewed literature is the importance of continuous training of cognitive
      functions, especially for people with cardiovascular risk.

PMID- 30302098
TI  - Acute, total occlusion of the left main stem: coronary intervention options,
      outcomes, and recommendations.
AB  - Introduction: Acute, total occlusion of the unprotected left main stem (uLMo) in
      acute coronary syndrome (ACS) patients is a catastrophic event often accompanied
      by sudden cardiac death (SCD) and/or cardiogenic shock (CS) with high mortality
      rates and limited methods of successful treatment. Emergent, surgical and
      percutaneous revascularization has been reported before, yet comprehensive data
      remains scarce. Aim: To examine emergency percutaneous coronary intervention
      (PCI) outcomes in ACS cases presenting with uLMo. Material and methods: Data on
      23 subjects undergoing primary PCI in uLMo cases were analyzed. The primary end
      point was in-hospital death; secondary end-points were successful salvage of
      coronary anatomy and 90-day major cardiac adverse events (MACE). Results: About
      40% of LM occlusion cases presented following successful on-site cardio-pulmonary
      resuscitation (CPR). Of all patients arriving for treatment the occluded LM was
      successfully opened and stented in ~90% of cases. CS was present in > 85% of
      cases, and circulatory support in the form of intra-aortic balloon pump and/or
      extracorporeal membrane oxygenation systems was applied in every eligible case
      (~80%). The in-hospital death rate was 56%, mostly including individuals
      requiring prior CPR. At 6 months, additional MACE rates were low at 8.7%.
      Conclusions: We found that uLMo ACS cases often present with preceding CPR and
      mostly in manifest CS. Coronary salvage is generally successful, yet uLMo even
      with optimal present day complex treatment yields quite high mortality rates.
      This is especially true for patients receiving prior CPR. In surviving patients,
      however, 6-month MACE rates are acceptable.

PMID- 30302099
TI  - Procedural advantages of a novel coronary stent design with ultra-thin struts and
      bioabsorbable abluminal polymer coating in an all-comers registry.
AB  - Introduction: The implications of novel drug-eluting stent (DES) design
      modifications including ultra-thin struts and new concepts of polymer coating for
      procedural efficacy are still unknown. Aim: To evaluate procedural efficacy and
      short-term safety of a novel DES design. Material and methods: In this all-comers
      registry, 407 consecutive patients were enrolled upon undergoing percutaneous
      coronary interventions (PCI) with the thin-strut bioabsorbable abluminal polymer
      coated SYNERGY stent. These patients were then compared with the previous 407
      patients undergoing PCI performed by the same interventionalists using currently
      established second-generation DES (Promus Element plus, Xience prime, Resolute
      Integrity). Several clinical and procedural data were compared, and the coronary
      artery complexity was assessed by the American College of Cardiology/American
      Heart Association classification and SYNTAX Score. Results: The study population
      consisted of 814 patients. A total of 859 Synergy stents were deployed in 480
      target vessels in the Synergy group (n = 407), and 904 stents in 469 vessels in
      the second-generation DES group (n = 407). Coincidentally, target lesions in the
      Synergy group (A 2.7%, B1 13.8%, B2 38.6%, C 45.0%) were more complex (p < 0.01)
      than those in the second-generation DES group (A 4.9%, B1 18.7%, B2 42.3%, C
      34.2%). In cases with severe lesions (B2/C), the median contrast agent amount and
      fluoroscopy time were significantly lower in the Synergy group, indicating
      improved deliverability (110 ml vs. 150 ml; p < 0.01 and 7.2 min vs. 9.1 min; p =
      0.01). Rates of in-hospital major adverse cardiovascular events were comparable
      between the two groups. Conclusions: In an all-comers, real-world PCI population,
      novel stent design modifications including ultra-thin struts and abluminal
      bioabsorbable polymer coating are associated with improved procedural
      performance.

PMID- 30302100
TI  - Temporal changes in the pattern of invasive angiography use and its outcome in
      suspected coronary artery disease: implications for patient management and
      healthcare resources utilization.
AB  - Introduction: Invasive coronary angiography (CAG), the 'gold standard' in
      coronary artery disease (CAD) diagnosis, requires hospitalization, is not risk
      free, and engages considerable healthcare resources. Aim: To assess recent
      (throught out 10 years) evolution of 'significant' (>= 50% stenosis(es)) CAD
      prevalence in subjects undergoing CAG for CAD diagnosis in a high-volume tertiary
      referral center. Material and methods: Anonymized medical records were compared
      for the last vs. the first 2-years of the decade (June 2007 to May 2018).
      Referrals for suspected CAD were 2067 of 4522 hospitalizations (45.7%) and 1755
      of 5196 (33.8%) respectively (p < 0.001). Results: The median patient age (64 vs.
      68 years) and the prevalence of heart failure (24.1% vs. 42.2%) increased
      significantly (p < 0.001). The CAG atherosclerotic lesions, for all stenosis
      categories (< 50%; >= 50%; >= 70%; occlusion(s)), were significantly more
      prevalent in men. The proportion of subjects with any atherosclerosis on CAG
      increased (80.7% vs. 77.6%, p = 0.015). However, in the absence of any gross
      change in, for instance, the fraction of women (40.4% vs. 41.8%), the proportion
      of CAGs with significant CAD (lesion(s) >= 50%) decreased from 55.2% in 2007/2008
      to below 1 in every 2 angiograms (48.9%) in 2017/2018 (p < 0.001). This
      unexpected finding occurred consistently across nearly all CAG referral
      categories. Conclusions: Despite more advanced age and a higher proportion of
      subjects with 'any' coronary atherosclerosis on CAG, the likelihood of a
      'negative' angiogram (lesion(s) < 50%; no further evaluation/intervention) has
      increased significantly over the last decade. The exact nature of this phenomenon
      requires further investigation, particularly as a reverse trend would be expected
      with the growing role (and current high penetration) of contemporary non-invasive
      diagnostic tools to rule out significant CAD.

PMID- 30302101
TI  - Does the effectiveness of recanalization of chronic occlusion depend on the
      location of the obstruction?
AB  - Introduction: In past studies, it has been questioned whether success of
      recanalization of chronic total occlusion (CTO) depends on the location of the
      occlusion - the circumflex artery (Cx) was considered as the most difficult to
      open. Aim: To determine whether the effectiveness of recanalization of CTO
      depends on the location of the obstruction. Material and methods: From January
      2011 to January 2016, a single operator dedicated to chronic total occlusions
      performed in our center 357 procedures on 337 patients. Results: Among 337
      patients included in the study, 83.4% were male. Mean age was 62.8 +/-9.3 years.
      Most of the patients had hypertension (86.4%) and hyperlipidemia (99.4%), and
      28.8% of them had diabetes. The most frequently opened artery was the right
      coronary artery (RCA; 52.4%), followed by the left anterior descending artery
      (LAD; 29.4%), and last the Cx (18.2%). The mean J-CTO score was comparable
      between the three groups. The success rate of recanalization of CTO was similar
      for all arteries: 84.5% in the RCA, 81.9% in the LAD and 89.2% in the Cx (overall
      p = 0.437). Neither procedural complications nor adverse events depended on the
      location of the CTO. Conclusions: Our study shows the same efficacy of CTO
      procedures of all epicardial arteries. We did not observe that effectiveness of
      recanalization of CTO depends on the location of the obstruction.

PMID- 30302102
TI  - Association of mean platelet volume and red blood cell distribution width with
      coronary collateral development in stable coronary artery disease.
AB  - Introduction: The prognostic value of hematological indices in cardiovascular
      diseases and the association between these parameters and cardiovascular
      conditions have been established in the literature. Aim: In this study, we aimed
      to investigate the relation of mean platelet volume (MPV), MPV to platelet ratio
      (MPR) and red cell distribution width (RDW) with degree of coronary collateral
      development (CCD) in stable coronary artery disease (CAD) subjects with
      established critical coronary artery stenosis. Material and methods: A total of
      306 patients with stable angina pectoris undergoing coronary arteriography were
      enrolled and divided on the basis of the development of CCD into two groups: a
      group with adequate CCD (n = 214) and a group with impaired CCD (n = 92). Routine
      complete blood count and biochemical parameters were measured before coronary
      arteriography. Results: The MPV and MPR levels were significantly higher in the
      inadequate CCD group (10.5 +/-1.8 fl vs. 8.7 +/-1.9 fl, p < 0.001 and 0.06 +/
      0.08 vs. 0.05 +/-0.07, p = 0.036). Patients with inadequate CCD had significantly
      higher RDW levels compared to patients with adequate CCD (15.5 +/-1.7% vs. 15.0
      +/-1.9%, p = 0.01). MPV and RDW were significantly associated with Rentrop
      collateral grading (r = -0.523, p < 0.001 and r = -0.239, p < 0.001,
      respectively), whereas the association with MPR was not significant. An MPV value
      greater than 9.95 fl, determined with ROC curve analysis, had 71% sensitivity and
      70% specificity in predicting inadequate CCD. An RDW greater than 14.3% has 71%
      sensitivity and 53% specificity in selecting patients with adequate CCD.
      Conclusions: The present study suggests that MPV and MPR may be associated with
      the degree of collateral development in chronic stable CAD. However, the negative
      association of RDW with inadequate CCD, in combination with previous
      contradictory reports, raises a doubt about the possible value of RDW in stable
      CAD. Although these parameters may be affected by various conditions, a high MPV
      may lead clinicians to suspect possible inadequate collateral development in
      stable CAD patients.

PMID- 30302103
TI  - Clinical factors predicting blood pressure reduction after catheter-based renal
      denervation.
AB  - Introduction: Renal denervation (RD) can lead to a significant and sustained
      decrease in mean values of arterial blood pressure (BP). However, there is still
      a subset of patients without a significant BP drop after RD (non-responders).
      Aim: To compare characteristics of RD responders to RD non-responders and to
      identify the clinical predictors of BP reduction. Material and methods: Thirty
      one patients with diagnosed resistant hypertension underwent RD. Three years
      after RD the analysis of BP reduction was performed in regard to the baseline
      patient characteristics. Results: After 3 years' follow-up a 10% or more
      reduction of systolic baseline BP was observed in 74% of patients. Ten percent or
      more reduction of diastolic baseline BP was observed in 71% of patients. Among
      responders we observed the following risk factors: hypercholesterolemia in 70%,
      body mass index (BMI) > 30 kg/m2 in 55%, diabetes mellitus in 35%, current
      smoking in 5%. Comorbidity included coronary artery disease (CAD) in 30%,
      cardiomyopathy in 10%, chronic obstructive pulmonary disease (COPD) in 10%, renal
      insufficiency in 10%, and ventricular arrhythmia in 5%. Among non-responders we
      observed the following risk factors: hypercholesterolemia in 38%, diabetes
      mellitus type 2 in 38% and BMI > 30 kg/m2 in 86%. Comorbidity included CAD in 50%
      and cardiomyopathy in 13% of patients. Conclusions: A 10% reduction of systolic
      baseline BP was observed in 74% of patients 3 years after renal denervation.
      Clinical factors like COPD, chronic kidney disease 3a, female sex and
      hypercholesterolemia increase the chances of effective reduction of BP.

PMID- 30302104
TI  - Increased risk profile in the treatment of patients with symptomatic degenerative
      aortic valve stenosis over the last 10 years.
AB  - Introduction: Currently, Cardiology Centres are overfilled with patients with
      degenerative aortic valve stenosis (DAS), usually eldery, with severe
      concommittant comorbidities, who are referred for further decisions and possible
      intervention. Aim: To evaluate changes in the risk profile of patients with
      severe DAS admitted to the cardiology department a decade ago compared with
      patients currently being admitted. Material and methods: We retrospectively
      evaluated all patients admitted with confirmed severe DAS, hospitalized during
      2005-2006 (group I: 140 patients) and in 2016 (group II: 152 patients), admitted
      for aortic valve intervention. A standard transthoracic echocardiogram,
      cardiovascular symptom and risk factor distribution, perioperative risk with the
      logistic EuroSCORE II and STS mortality scores were obtained. Results: Patients
      in group II were significantly older (p < 0.001), had more cardiovascular risk
      factors, and more often presented with atrial fibrillation (27% vs. 11.4%, p =
      0.001), renal impairment (34.9% vs. 22.8%; p = 0.024), severe lung disease (17.1%
      vs. 2.1%, p < 0.001), and extracardiac arteriopathy (40.1% vs. 17.8%, p < 0.001).
      The aortic valve area (AVA) (p = 0.356), mean-transvalvular pressure gradient (p
      = 0.215), and left ventricular ejection fraction (p = 0.768) were similar in both
      groups. However, the prevalence of pulmonary hypertension, severe mitral
      regurgitation, and low-flow, low-gradient DAS were 3.1-, 8.4- and 1.84-fold more
      frequent in group II than group I. The percentages of subjects with EuroSCORE II
      and STS scores >= 4% in 2005-2006 were 7.1% and 6.4%, as compared to 27% and
      26.3% in 2016 (both p < 0.001). 22% of patients in 2016, as compared to 31% in
      2005/2006, were considered ineligible for DAS intervention. Conclusions: In just
      a decade, the risk profile of patients admitted with DAS has increased hugely,
      mainly due to older age, accumulation of comorbidities and more advanced disease
      at presentation. Although transcatheter aortic valve intervention has expanded
      the indications for intervention in high-risk patients, the number of patients
      disqualified from interventional treatment remains high.

PMID- 30302105
TI  - Silent ischemic brain lesions detected by multi-slice computed tomography are
      associated with subclinical atrial fibrillation in patients with cardiac
      resynchronization therapy.
AB  - Introduction: There is insufficient research on the relationship between
      subclinical atrial fibrillation (SCAF) and silent ischemic brain lesions (IBLs).
      Aim: To investigate the relationship between SCAF and silent IBLs in patients
      with cardiac resynchronization therapy (CRT). Material and methods: Of 720 CRT
      implanted patients in our department between 2012 and 2018, 121 patients who
      underwent elective cranial multi-slice computed tomography (MSCT) during their
      follow-up were included in our study. Atrial high-rate episodes (AHRE) were
      detected by the CRT device. Subclinical atrial fibrillation was defined as
      asymptomatic AHRE longer than 6 min and shorter than 24 h. A cranial MSCT scan
      was performed using a 128-section scanner with contiguous 2-5 mm axial images.
      Patients were divided into two groups - with and without silent IBL. Results:
      Silent IBLs were detected in 21 (17.4%) of 121 patients with CRT. Ischemic brain
      lesion presence was found to be associated with age, CHA2DS2-VASc score, left
      ventricular (LV) ejection fraction (EF), hypertension and SCAF in univariate
      analysis (p < 0.05). In multivariate regression analysis, presence of SCAF and
      LVEF were found to be independent parameters predicting the risk of silent IBLs.
      According to this analysis, the presence of SCAF and every 1% decrease in LVEF
      were found to increase the risk of silent IBL by 3.5 times and 14.8%,
      respectively. Conclusions: Subclinical atrial fibrillation is independently
      associated with silent IBL presence. Patients with CRT should be closely
      monitored for SCAF. Patients diagnosed with SCAF should be evaluated for IBL
      development and treated with the appropriate oral anticoagulant.

PMID- 30302106
TI  - Comparison of clinical and echocardiographic outcomes and quality of life in
      patients with severe mitral regurgitation treated by MitraClip implantation or
      treated conservatively.
AB  - Introduction: The most common alternative method of treatment for patients with
      severe mitral regurgitation (MR) is the implantation of a MitraClip device. Aim:
      To evaluate clinical and echocardiographic outcomes and quality of life (QoL) in
      patients with severe secondary MR, disqualified from surgical intervention,
      treated by implantation of a MitraClip in comparison to conservative therapy.
      Material and methods: A total of 33 patients were included. Patients were
      stratified by treatment method: group A, MitraClip implantation (n = 10); group
      B, conservative treatment (n = 23). Clinical, echocardiographic, and QoL (EQ-5D
      3L, SF-12v2 Health Survey) characteristics were compared at baseline and at
      follow-up of 8.0 +/-2.3 months. Results: In group A, 2 deaths were observed: one
      patient died 7 days after MitraClip implantation, and the second patient died 4
      months after the procedure. No cases of rehospitalization were reported. In group
      B, 4 (17.4%) deaths and 6 (26.1%) hospitalizations were reported. After MitraClip
      implantation a significant reduction of the NYHA class (p = 0.02), decrease in
      grade of MR (p = 0.01), vena contracta width (p = 0.006), effective regurgitant
      orifice area (EROA) (p = 0.003), regurgitant volume (p = 0.03) and end-diastolic
      left ventricle diameter (p = 0.02) as well as an improvement in QoL were
      reported. There were no significant changes in the NYHA class and QoL in the
      group treated conservatively. In those patients, we observed increased
      intercommissural mitral annulus diameter (p = 0.03), left atrium diameter (p =
      0.002), and right ventricle dimension (p = 0.008), more severe tricuspid
      regurgitation (p = 0.02) and lower mitral annular plane systolic excursion (p =
      0.01). Conclusions: Patients with severe secondary MR treated with the MitraClip
      achieved a significant reduction in symptoms and MR grade, as well as an
      improvement in QoL, as compared to patients treated conservatively.

PMID- 30302107
TI  - Mehran in-stent restenosis classification adapted for coronary bifurcations: the
      impact on 4-year follow-up from randomized clinical studies POLBOS I and II.

PMID- 30302108
TI  - Bail-out use of the Amplatzer Septal Occluder for treatment of acute iatrogenic
      leaflet perforation during the MitraClip procedure in a patient with functional
      mitral regurgitation.

PMID- 30302109
TI  - Zero-contrast percutaneous coronary intervention of saphenous vein graft in a
      patient with chronic renal failure.

PMID- 30302110
TI  - Left superior vena cava draining to left atrium with partially anomalous
      pulmonary venous connection and left-to-right shunt - multimodality imaging and
      percutaneous treatment.

PMID- 30302111
TI  - Hypoplastic left heart syndrome with anomalous circumflex artery arising from
      left pulmonary artery. A description of combined surgical and interventional
      cardiac treatment.

PMID- 30302112
TI  - Lead externalization - a potential source of lead-related infective endocarditis?

PMID- 30302113
TI  - Sudden cardiac arrest in the course of takotsubo syndrome in a 15-year-old girl.

PMID- 30302114
TI  - Eosinophilic fasciitis: a case series with an emphasis on therapy and induction
      of remission.
AB  - Eosinophilic fasciitis is an uncommon connective tissue disorder that affects
      patients of all ages, resulting in significant morbidity. Systemic
      corticosteroids can induce remission of disease. However, there is no universally
      accepted treatment ladder for eosinophilic fasciitis. This case series evaluates
      treatment efficacy in patients with eosinophilic fasciitis seen at Wake Forest
      University Department of Dermatology outpatient clinics. Patient charts were
      screened using ICD-9 diagnosis code 710.9 (unspecified diffuse connective tissue
      disease) to identify patients with eosinophilic fasciitis (n=10) seen at our
      institution. Patients were treated for an average 24 months with a combination of
      methotrexate and prednisone therapy, unless one or both were contraindicated,
      with each medication tapered conservatively to prevent disease flares. Alternate
      treatments included mycophenolate mofetil with prednisone, azathioprine with
      prednisone, prednisone monotherapy, and methotrexate monotherapy. Disease
      remission off therapy and on low-dose therapy was 66 and 70%, respectively. Our
      first-line therapy of concomitant methotrexate and prednisone is well-tolerated
      and effective for managing patients with eosinophilic fasciitis. Our study was
      limited to cases seen at a single academic institution.

PMID- 30302115
TI  - The biosimilars journey: current status and ongoing challenges.
AB  - Biosimilar products are already approved and marketed in several countries. The
      Food and Drug Administration has approved ten different biosimilars, and the
      European Medicines Agency has approved 40. Even though this scenario has provided
      important experience with biosimilar products, there are still challenges and
      unanswered questions. Up to now, a good amount of knowledge has been gathered in
      order to support the importance of the totality of evidence and the construction
      of a biosimilarity exercise for regulatory approval. In addition, the
      extrapolation of indications has been proved viable when a careful analysis is
      performed. The models for clinical trials and the use of the most sensible
      populations have been extensively discussed, and there is apparent homogeneity in
      manufacturer choices for study designs. However, some challenges remain. The lack
      of regulatory harmony, especially concerning naming, the marketed intended
      copies, the interchangeability, and the biosimilars in orphan diseases are some
      of those and are the focus of discussion in this review.

PMID- 30302116
TI  - Comparative Proteomic Analysis of Two Differently Extracted Coptis chinensis in
      the Treatment of Type 2 Diabetic Rats.
AB  - Coptis chinensis (CC) is widely used to treat diabetes in traditional Chinese
      medicine due to its significant hypoglycemic and hypolipidemic effects. It was
      reported that CC powders are more effective than CC decoctions. In this study, a
      rat model of type 2 diabetes was established and treated with supercritical
      extracted CC and gastric juice extracted CC, respectively. Body weight, fasting
      plasma insulin, insulin resistance index, and lipid profiles were measured along
      with oral glucose tolerance tests (OGTTs). In addition, the levels of plasma
      proteins were compared between type 2 diabetic rats and CC-treated rats using an
      iTRAQ-based quantitative proteomic analysis. The results showed that the plasma
      levels of triglyceride (TC), total cholesterol (TG), and low-density lipoprotein
      (LDL) in rats of both CC-treated groups were significantly decreased. In
      addition, the proteomic analysis identified 929 proteins, while 15 proteins were
      selected from these 929 proteins based on their expression levels and
      bioinformatic results. Among these 15 proteins, 9 proteins (IGF-1, Igfbp4, Igfbp
      6, Igfals, C2, C4, Cfi, Prdx-2, and Prdx-3) were upregulated in the two CC
      treated groups, while 6 proteins (Pla2g7, Pcyox1, ApoC-1, ApoC-3, ApoB-100, and
      ApoE) were downregulated. The functions of these proteins are associated with
      glucose metabolism, insulin action, immunity, inflammation, lipid metabolism,
      oxidation, and antioxidation. The two differently extracted CC did not show
      significant differences in terms of their treatment efficacy. This research
      expanded our understanding on the therapeutic effects and mechanisms of CC in the
      treatment of type 2 diabetes.

PMID- 30302117
TI  - Major Depression in Chinese Medicine Outpatients with Stagnation Syndrome:
      Prevalence and the Impairments in Well-Being.
AB  - Stagnation syndrome, a diagnostic entity in traditional Chinese medicine (TCM),
      has been long regarded as the TCM counterpart of major depression in Western
      medicine. The study investigated the prevalence of major depression among
      stagnation syndrome patients and evaluated their well-being and functioning
      outcomes. In total, 117 patients diagnosed with stagnation syndrome were measured
      using Stagnation Scale, the Patient Health Questionnaire-9 (PHQ-9), and the Body
      Mind-Spirit Well-Being Inventory. Results indicate major depression among
      stagnation syndrome patients was characterized by a high co-occurrence rate and
      worse physical, mental, and functional outcomes. More than one-quarter (26.5%) of
      the patients met the DSM-V diagnostic criteria for major depression and over half
      (53%) exceeded the PHQ-9 cutoff (score above 10) for moderate/severe depression
      symptoms. The wellness of the stagnation syndrome patients was worse (M = 298.2,
      SD = 66.5) than that of the general population (M = 360.9, SD = 79.9), with a
      large Cohen's d value of 0.9. The "wellness outlook" of the depressed stagnation
      syndrome patients appeared grimmer (M = 252.3, SD = 52.2). The correlation
      between stagnation and depression was higher for affective symptoms than somatic
      symptoms. Physical distress did not mediate the relationship between stagnation
      and daily functioning. These might suggest that stagnation syndrome and major
      depression may share some similar psychological mechanisms.

PMID- 30302118
TI  - Chinese Medicinal Herbs in the Treatment of Diabetic Cognitive Impairment: A
      Systematic Review and Meta-Analysis.
AB  - Background: Diabetic cognitive impairment (DCI), a serious complication of
      diabetes mellitus (DM), is gaining more acceptance and attention. The learning
      and memory function of diabetics always decreases. Traditional Chinese medicine
      (TCM) has been demonstrated to be effective in treating the symptoms in China,
      and thereinto Chinese medicinal herbs (CMH) are the most widely used. The
      objective of the present study was to review and analyze the existing data about
      reducing the symptoms in CMH treatment for DCI. Methods: Electronic literature
      databases (PubMed, EMBASE, CNKI, SinoMed, and Wan fang) were searched for
      randomized controlled trials conducted in China, comparing CMH with western
      medicines in the treatment of DCI, up to April 1, 2018. We applied standard meta
      analytic techniques to analyze data from papers that reached acceptable criteria.
      Result: Nine randomized controlled trials (n = 576) on CMH were included. We
      found moderate evidence that CMH used alone or in combination with western
      medicines was more effective than western medicines alone in reliving the
      symptoms for DCI (total effective rate, odds radio (OR) = 4.64 (2.60, 8.29), and
      95% confidence interval, P<0.00001). Besides, CMH along or in combination with
      western medicines showed more beneficial effects on Montreal Cognitive Assessment
      (MoCA) scale (mean difference (MD) = 1.31(0.75, 1.87), P<0.00001), Mini-Mental
      State Examination (MMSE) scale (MD = 2.07 (0.86, 3.28), P<0.00001, and TCM
      symptom score (TCMSS) (MD = -4.89 (-8.44, -1.34), P = 0.007). Most of the
      included studies showed that there was not a significant difference in the
      adverse events. Conclusions: These findings demonstrated that CMH used alone or
      in combination with western medicines were apparently better than western
      medicines alone in the treatment of DCI. Because of the poor quality of the
      studies that were available for the present meta-analysis, further researches are
      still needed to support these early findings.

PMID- 30302119
TI  - Biological Evaluation of Different Extracts of Aerial Parts of Nepeta deflersiana
      and Standardization of Active Extracts Using 8-Epi-7-Deoxyloganic Acid and
      Ursolic Acid by Validated HPTLC Method.
AB  - Nepeta deflersiana (Lamiaceae) is a well-known medicinal plant that grows in
      Saudi Arabia. This plant is used in Saudi and Yemeni folk medicine as an anti
      inflammatory, carminative, and antirheumatic agent. In order to prove its use in
      folk medicine, four different extracts from the aerial parts of the plant:
      petroleum ether, chloroform, ethyl acetate, and n-butanol extracts were subjected
      to biological assays to screen PPARalpha and PPAR Upsilon agnostic, antioxidant,
      anti-inflammatory, and cytotoxic activities. Ethyl acetate and n-butanol extracts
      of N. deflersiana NDEE and NDBE, respectively, showed a decrease in oxidative
      stress and inhibition of both NF-kB and iNOS activities with no cytotoxic effects
      on four human cancer cell lines. Both active extracts were standardized using two
      bioactive metabolites which were isolated from the aerial parts of the same plant
      [8-epi-7-deoxyloganic acid (compound 1) and Ursolic acid (compound 2)] by
      developing a validated HPTLC method. It was found to provide a sharp and compact
      band of compound 1 at Rf = 0.07 and Rf = 0.57 for compound 2, using chloroform,
      methanol, and formic acid (8.9:0.8:0.3, v/v/v) as mobile phase at 550 nm.
      Compounds 1 and 2 were found in NDEE by 9.59 %, w/w, and 84.63 %, w/w,
      respectively, and by 11.97 %, w/w, and 21.26 %, w/w, respectively, in NDBE.

PMID- 30302120
TI  - Oplopanax horridus: Phytochemistry and Pharmacological Diversity and Structure
      Activity Relationship on Anticancer Effects.
AB  - Oplopanax horridus, well-known as Devil's club, is probably the most important
      ethnobotanical to most indigenous people living in the Pacific Northwest of North
      America. Compared with the long history of traditional use and widespread
      distribution in North America, the study of O. horridus is relatively limited. In
      the past decade, some exciting advances have been presented on the phytochemistry
      and pharmacological diversity and structure-activity relationship on anticancer
      effects of O. horridus. To date, no systematic review has been drafted on the
      recent advances of O. horridus. In this review, the different phytochemicals in
      O. horridus are compiled, including purified compounds and volatile components.
      Animal and in vitro studies are also described and discussed. Especially, the
      potential structural-activity relationship of polyynes on anticancer effects is
      highlighted. This review aimed to provide comprehensive and useful information
      for researching O. horridus and finding potential agents in drug discovery.

PMID- 30302121
TI  - Effects of exenatide versus insulin glargine on body composition in overweight
      and obese T2DM patients: a randomized controlled trial.
AB  - Background: Weight loss, especially fat mass reduction, helps to improve blood
      glucose control, insulin sensitivity, and beta-cell function. This study aimed to
      compare the effect of exenatide and glargine on body composition in overweight
      and obese patients with type 2 diabetes (T2DM) who do not achieve adequate
      glycemic control with metformin. Methods: We performed a prospective, randomized
      study of 37 overweight or obese patients with T2DM who had inadequate glycemic
      control with metformin. The patients were treated with either exenatide or
      glargine for 16 weeks. Dual-energy X-ray absorptiometry was used to assess body
      composition. Results: Post-intervention weight, body mass index (BMI), waist
      circumference, body mass, and fat mass were lower in patients treated with
      exenatide, while weight and BMI significantly increased with glargine. Reductions
      in weight, BMI, body fat mass, and percent fat mass (except for gynoid) were
      greater with exenatide than with glargine, and percent lean tissue (other than
      the limbs) increased with exenatide. In all body regions except for the limbs,
      fat mass decreased with exenatide to a greater extent than lean tissue. Glucose
      control, insulin resistance, and beta-cell function were not different between
      the treatment groups. Conclusions: For overweight and obese patients whose T2DM
      was inadequately controlled with metformin, exenatide and glargine achieved
      similar improvements in glycemic control, insulin sensitivity, and beta-cell
      function.However, exenatide produced better weight and fat mass reduction, which
      were beneficial for blood glucose control. Our findings may guide the selection
      of appropriate drugs for glycemic and weight control. Trial registration:
      NCT02325960, registered 25 December 2014.

PMID- 30302123
TI  - A New Approach for Advertising CTR Prediction Based on Deep Neural Network via
      Attention Mechanism.
AB  - Click-through rate prediction is critical in Internet advertising and affects web
      publisher's profits and advertiser's payment. The traditional method of obtaining
      features using feature extraction did not consider the sparseness of advertising
      data and the highly nonlinear association between features. To reduce the
      sparseness of data and to mine the hidden features in advertising data, a method
      that learns the sparse features is proposed. Our method exploits dimension
      reduction based on decomposition, takes advantage of the attention mechanism in
      neural network modelling, and improves FM to make feature interactions contribute
      differently to the prediction. We utilize stack autoencoder to explore high-order
      feature interactions and use improved FM for low-order feature interactions to
      portray the nonlinear associated relationship of features. The experiment shows
      that our method improves the effect of CTR prediction and produces economic
      benefits in Internet advertising.

PMID- 30302124
TI  - Risk factors for mortality in the late amputation of necrotizing fasciitis: a
      retrospective study.
AB  - Background: Necrotizing fasciitis (NF) is a rapidly progressive infectious
      disease that primarily involves the fascia and subcutaneous tissue. If not
      promptly treated, it can lead to morbidity as well as mortality. It can affect
      any part of the body, most commonly the extremities. Early and aggressive
      surgical treatment is the proper way of management. The purpose of this study was
      to identify the risk factors for mortality in late amputation among NF patients
      that may be used in routine clinical practice to prevent mortality. Methods: A
      retrospective cohort study of hospitalized patients with NF was conducted in a
      tertiary teaching hospital in Taiwan between March 2015 and March 2018. All
      collected data were statistically analyzed. Results: A total of 582 patients with
      NF were included; 35 of them had undergone amputation (7 primary and 28 late
      amputations), with a 6% amputation rate. Thirteen amputated patients still died
      eventually (all in the late amputation group). Significant risk factors for
      mortality identified in the late amputation group included hemorrhagic bullae (p
      = 0.001, OR 4.7, 95% confidence interval (CI) 2.68-8.69), peripheral vascular
      disease (p < 0.001, OR 3.2, 95% CI 1.12-10.58), bacteremia (p = 0.021, OR 2.87,
      95% CI 2.07-5.96), and Laboratory Risk Indicator of Necrotizing Fasciitis
      (LRINEC) score > 8 (p < 0.001, OR 1.97, 95% CI 1.28-4.61). Vibrio vulnificus was
      the main causative organism based on our study, but the microbiology results
      showed no significant correlation. Conclusion: NF patients with hemorrhagic
      bullae, comorbidity with peripheral vascular disease, presence of bacteremia, or
      LRINEC score > 8 should receive early and primary amputation in order to prevent
      mortality.

PMID- 30302122
TI  - MicroRNAs from plants to animals, do they define a new messenger for
      communication?
AB  - MicroRNAs (miRNAs), a class of single-stranded non-coding RNA of about 22
      nucleotides, are potent regulators of gene expression existing in both plants and
      animals. Recent studies showed that plant miRNAs could enter mammalian
      bloodstream via gastrointestinal tract, through which access a variety of tissues
      and cells of recipients to exert therapeutic effects. This intriguing phenomenon
      indicates that miRNAs of diet/plant origin may act as a new class of bioactive
      ingredients communicating with mammalian systems. In this review, in order to
      pinpoint the reason underlying discrepancies of miRNAs transmission from
      diet/plant to animals, the pathways that generate miRNAs and machineries involved
      in the functions of miRNAs in both kingdoms were outlined and compared. Then, the
      current controversies concerning cross-kingdom regulations and the potential
      mechanisms responsible for absorption and transfer of diet/plant-derived miRNAs
      were interpreted. Furthermore, the hormone-like action of miRNAs and the
      intricate interplay between miRNAs and hormones were implicated. Finally, how
      these findings may impact nutrition and medicine were briefly discussed.

PMID- 30302125
TI  - UK clinical experience up to 52 weeks with linaclotide for irritable bowel
      syndrome with constipation.
AB  - Background: Linaclotide, a guanylate cyclase C agonist, has been shown in
      clinical trials to improve symptoms of irritable bowel syndrome with constipation
      (IBS-C). Here we report data from a real-world study of linaclotide in the UK.
      Methods: This 1-year, multicentre, prospective, observational study in the UK
      enrolled patients aged 18 years and over initiating linaclotide for IBS-C. The
      primary assessment was change from baseline in IBS Symptom Severity Scale (IBS
      SSS) score at 12 weeks, assessed in patients with paired baseline and 12-week
      data. Change from baseline in IBS-SSS score at 52 weeks was a secondary
      assessment. Adverse events were recorded. Results: In total, 202 patients were
      enrolled: 185 (91.6%) were female, median age was 44.9 years (range 18.1-77.2)
      and 84 (41.6%) reported baseline laxative use. Mean (standard deviation) baseline
      IBS-SSS score was 339 (92), with most patients (n = 129; 66.8%) classified as
      having severe disease (score ?300). In patients with paired data, there was a
      significant mean (95% confidence interval) decrease in IBS-SSS score from
      baseline to 12 weeks [-77.0 (-96.3, -57.7); p < 0.001; n = 124] and baseline to
      52 weeks [-70.7 (-95.0, -46.5); p < 0.001; n = 76]. Overall, 174 adverse events
      were reported in 77 (38.1%) patients, most commonly diarrhoea (n = 54; 26.7%),
      abdominal pain (n = 21; 10.4%) and abdominal distension (n = 13; 6.4%).
      Conclusion: Linaclotide significantly improved IBS-SSS score at 12 and 52 weeks.
      These results provide insights into outcomes with linaclotide treatment over 1
      year in patients with IBS-C in real-world clinical practice.

PMID- 30302126
TI  - Food and Drug Administration guidances on biosimilars: an update for the
      gastroenterologist.
AB  - The management of inflammatory bowel disease (IBD), a significant cause of
      morbidity in the United States (US), has been revolutionized over the last two
      decades by the introduction of biologic therapies. These include antitumor
      necrosis factor alpha (TNF-alpha) agents. Since 2016, five biosimilar TNF-alpha
      inhibitors have been approved by the US Food and Drug Administration (FDA) for
      use in the treatment of IBD. The FDA has published a series of guidance documents
      related to the evaluation, licensing, and approval of biosimilars. The aim of
      this review is to provide an overview of these FDA guidances and the issues
      associated with biosimilars in the US.

PMID- 30302127
TI  - Drug holiday in patients with polycystic liver disease treated with somatostatin
      analogues.
AB  - Background: Somatostatin analogues (SAs) reduce liver volume and relief symptoms
      in polycystic liver disease (PLD). Its effect wears off after continuing therapy
      suggesting development of SA tolerance in patients on chronic therapy. We
      postulate that a drug holiday resensitizes the liver to its acute pharmacological
      effects. Therefore, this study examines the liver volume-reducing effect of SAs
      after a drug holiday. Methods: Patients were identified from the International
      PLD Registry and included in our analysis when (1) treated with SAs during two
      cycles separated by a drug holiday and (2) height-adjusted total liver volume
      (hTLV) was available at start and end of each cycle. For our primary outcome we
      compared the effect of SAs (in % per 6 months) on hTLV between the first and
      second treatment cycle. Results: In 34 patients, initial liver volume-reducing
      effect was similar to that after rechallenge [-2.6% per 6 months (interquartile
      range, -3.8-0.8) versus -1.6% per 6 months (interquartile range, -3.1-1.1), p =
      0.510]. Cessation of treatment led to a rebound effect, but liver volume remained
      stable compared with the baseline with intermittent therapy in responders to SA [
      0.6% (interquartile range, -7.4-5.7) after 46.5 months]. Conclusions: PLD
      patients treated with SAs benefit from retreatment after a drug holiday. The
      significant increase of liver volume after cessation of treatment complicates
      widespread use of a drug holiday as new treatment strategy. Our results
      contribute to a better understanding of the pharmacological effect of SAs and
      help to identify patients who might benefit.

PMID- 30302128
TI  - Effect of plano-valgus foot posture on midfoot kinematics during barefoot walking
      in an adolescent population.
AB  - Background: Plano-valgus is a common alteration of the paediatric foot,
      characterized by valgus hindfoot, foot pronation and drop of the medial
      longitudinal arch. Despite their importance in the diagnosis and classification
      of plano-valgus foot condition, little information is available on functional
      alterations of the major joints spanning the medial longitudinal arch - i.e.
      midtarsal and tarso-metatarsal. Aim of the study was to provide objective
      description of the alterations in plano-valgus midfoot joints with respect to
      those in an age-matched normally-developed feet population. Methods: Twenty
      adolescents (13.3 +/- 0.8 years) with bilateral plano-valgus feet underwent
      clinical examination and were gait-analysed via a validated 4-segment foot model.
      This allowed to measure static foot posture, kinematics of the main foot joints,
      and medial longitudinal arch deformation during walking at comfortable speed.
      Range of motion and temporal profiles of joint rotations were compared to those
      from a control population of age-matched adolescents with normally-developed
      feet. Results: The plano-valgus midtarsal joint was more dorsiflexed, everted and
      abducted than that in the control group, and showed reduced sagittal-plane RoM
      (plano-valgus = 15.9 degrees; control = 22.2 degrees; P <  0.01). The tarso
      metarsal joint was more plantarflexed and adducted, and showed larger frontal
      plane RoM. The MLA showed larger RoM and was lower throughout the stance phase of
      the gait cycle. Conclusion: Significant postural and kinematic alterations are
      present at the midtarsal and tarso-metarsal joints of adolescents with plano
      valgus feet. Objective identification and quantification of plano-valgus foot
      alterations, via non-invasive gait-analysis, is relevant to improving the
      diagnosis of this condition and to evaluating the effect of conservative
      treatments and of surgical corrections by different techniques.

PMID- 30302129
TI  - Combined effect of glycemic and blood pressure control on diabetic retinopathy
      among Chinese with type-2 diabetes mellitus.
AB  - Background: To explore the associations of glycemic and blood pressure (BP)
      control with diabetic retinopathy (DR), with special focus on whether different
      combinations of categories of these two interventions are additive. Methods: A
      community-based survey including 913 patients with known type-2 diabetes mellitus
      (T2DM) was conducted in Suzhou, China. Retinal photographs were graded for the
      presence of DR using the Airlie House classification system. BP and blood
      hemoglobin A1c (HbA1C) levels were measured by standardized protocols. Binary
      logistic regression models were established to examine the associations of risk
      factors with DR. Results: The overall prevalence of any DR was 18.0% [95%
      confidence interval (95% CI) 15.5-20.6%] in this population. Stratified by
      conventional control thresholds, lower levels of either systolic blood pressure
      (SBP, < 140 mmHg) or HbA1C (< 7.0%) were not significantly associated with
      decreased susceptibility to DR, while patients simultaneously with lower HbA1C
      and SBP levels demonstrated 43% reduced likelihood of developing DR [adjusted
      odds ratio (OR) = 0.57, 95% CI 0.33-0.99, P = 0.045)], comparing with those with
      both higher levels of HbA1C (>= 7.0%) and SBP (>= 140 mmHg). Meanwhile, the group
      achieved intensive HbA1C (< 6.5%) and SBP (< 120 mmHg) control goals were found
      to have the smallest OR, but failed in yielding statistical significance (P =
      0.10). Conclusions: In this community-based DR screening study of Chinese adults
      with T2DM, combination but not individual of lower SBP (< 140 mmHg) and HbA1C (<
      7.0%) levels, were suggested to be associated with a significantly reduced
      likelihood of having DR.

PMID- 30302130
TI  - Primary cilium and glioblastoma.
AB  - Glioblastoma (GBM) represents the most common, malignant and lethal primary brain
      tumour in adults. The primary cilium is a highly conserved and dynamic organelle
      that protrudes from the apical surface of virtually every type of mammalian cell.
      There is increasing evidence that abnormal cilia are involved in cancer
      progression, since primary cilia regulate cell cycle and signalling transduction.
      In this review, we summarize the role of primary cilium specifically with regard
      to GBM, where there is evidence postulating it as a critical mediator of GBM
      tumorigenesis and progression. This opens the way to the application of cilia
      targeted therapies ('ciliotherapy') as a new approach in the fight against this
      devastating tumour.

PMID- 30302131
TI  - Effect of statins on oxidative DNA damage in diabetic polyneuropathy.
AB  - Oxidative stress induces nerve damage in type 2 diabetes mellitus and leads to
      diabetic polyneuropathy (DPN) and can affect the DNA and antioxidant status.
      Statins have pleiotropic, protective effects on the peripheral nerves of patients
      with diabetes. The aim of this study was to determine the effects of
      ezetimibe/simvastatin and rosuvastatin on DNA damage in patients with DPN. This
      randomized, double-blind, placebo-controlled, clinical trial comprised
      outpatients from Guadalajara, Mexico. The inclusion criteria were either gender,
      age 35-80 years, type 2 diabetes, glycated hemoglobin <=10%, diabetic
      polyneuropathy stage 1/2, and signed informed consent. Patients who were taking
      antioxidant therapy or statins, had hypersensitivity to drugs, experienced organ
      failure, were pregnant or breastfeeding, or had other types of neuropathy were
      excluded. We assigned patients to placebo, ezetimibe/simvastatin 10/20 mg, or
      rosuvastatin 20 mg, and the primary outcomes were 8-hydroxy-2'-deoxyguanosine (8
      OHdG) for DNA damage, 8-oxoguanine-DNA-N-glycosilase (hOGG1) for DNA repair, and
      superoxide dismutase (SOD). Seventy-four patients were recruited. Nine patients
      were included as negative controls. There were no differences in 8-OHdG between
      the healthy subjects (4.68 [3.53-6.38] ng/mL) and the DPN patients (4.51 [1.22
      9.84] ng/mL), whereas the hOGG1 level was 0.39 (0.37-0.42) ng/mL in the healthy
      subjects and 0.41 (0.38-0.54) ng/mL in patients with DPN at baseline (p = 0.01).
      SOD decreased significantly in patients with DPN (5.35 [0.01-17.90] U/mL)
      compared with the healthy subjects (9.81 [8.66-12.61] U/mL) at baseline (p <
      0.001). No significant changes in DNA biomarkers were observed in any group
      between baseline and final levels. We noted a rise in hOGG1 in patients with DPN,
      without modifications after treatment. There was a slight, albeit insignificant,
      increase in SOD in patients who were on statins.

PMID- 30302132
TI  - Engineering the hard-soft tissue interface with random-to-aligned nanofiber
      scaffolds.
AB  - Tendon injuries can be difficult to heal and have high rates of relapse due to
      stress concentrations caused by scar formation and the sutures used in surgical
      repair. Regeneration of the tendon/ligament-to-bone interface is critical to
      provide functional graft integration after injury. The objective of this study is
      to recreate the tendon-to-bone interface using a gradient scaffold which is
      fabricated by a one-station electrospinning process. Two cell phenotypes were
      grown on a poly-epsilon-caprolactone nanofiber scaffold which possesses a gradual
      transition from random to aligned nanofiber patterns. We assessed the effects of
      the polymer concentration, tip-to-collector distance, and electrospinning time on
      the microfiber diameter and density. Osteosarcoma and fibroblast cells were
      seeded on the random and aligned sections of scaffolds, respectively. A random-to
      aligned cocultured tissue interface which mimicked the native transition in
      composition of enthesis was created after 96 h culturing. The results showed that
      the microstructure gradient influenced the cell morphology, tissue topology, and
      promoted enthesis formation. This study demonstrates a heterogeneous nanofiber
      scaffold strategy for interfacial tissue regeneration. It provides a potential
      solution for mimicking transitional interface between distinct tissues, and can
      be further developed as a heterogeneous cellular composition platform to
      facilitate the formation of multi-tissue complex systems.

PMID- 30302133
TI  - Treatment and evaluation of dysphagia rehabilitation especially on suprahyoid
      muscles as jaw-opening muscles.
AB  - In our aging society, the number of patients with dysphagia, which is associated
      with disease and aging, is rapidly increasing. The swallowing reflex is a complex
      process that involves coordinated contractions of swallowing muscles. Many
      researchers have reported that age-related changes, such as frailty and
      sarcopenia, affect swallowing muscles and contribute to the decline in the
      swallowing function. Thus, simple, non-invasive evaluation methods and exercises
      for swallowing muscles in elderly patients with dysphagia are important. Anterior
      superior hyolaryngeal elevation during swallowing results from contractions of
      the suprahyoid muscle, which plays a primary role in opening the upper esophageal
      sphincter, along with relaxation of the cricopharyngeal muscle and laryngeal
      closure. Thus, many researchers have studied methods for evaluating and
      augmenting suprahyoid muscles. On the other hand, some researchers have reported
      on dysphagia rehabilitation focused on jaw-opening actions, because hyolaryngeal
      elevation muscles correspond with jaw-opening muscles. In this study, we describe
      a new dysphagia evaluation method and an exercise that focuses on suprahyoid
      muscles with application of jaw-opening actions.

PMID- 30302134
TI  - Effects of blue-light irradiation during dental treatment.
AB  - In dentistry, blue light is widely used for tooth bleaching and restoration
      procedures involving composite resin. In addition, many dentists use
      magnification loupes to enable them to provide more accurate dental treatment.
      Therefore, the use of light is indispensable in dental treatment. However, light
      can cause various toxicities, and thermal injuries caused by light irradiation
      are regarded as particularly important. In recent years, the eye damage and non
      thermal injuries caused by blue light, the so-called "blue light hazard", have
      gained attention. Unfortunately, much of the research in this field has just
      begun, but our recent findings demonstrated that blue-light irradiation generates
      reactive oxygen species (ROS) and induces oxidative stress in oral tissue.
      However, they also showed that such oxidative stress is inhibited by
      antioxidants. There have not been any reports that suggested that the ROS-induced
      phototoxicity associated with blue-light irradiation causes direct clinical
      damage, but some disorders are caused by the accumulation of ROS. Therefore, it
      is presumed that it is necessary to suppress the accumulation of oxidative
      stressors in oral tissues during treatment. In the future, we have to promote
      discussion about the suppression of phototoxicity in dentistry, including
      concerning the use of antioxidants to protect against phototoxic damage.

PMID- 30302135
TI  - Mastication as a tool to prevent cognitive dysfunctions.
AB  - Mastication as we all know has always been related to its primary function of
      digestion, but little do we know that it produces an enhancing effect on general
      health, especially the cognitive performance related aspects of memory. Recent
      studies have shown its association with activation of various brain regions,
      however little is known about its effects on neuronal activity in these specified
      regions. According to the enormous evidences collected so far, mastication has
      proved to be effective in conducting huge amount of sensory information to the
      brain, and maintaining learning and memory functions of hippocampus. Therefore it
      is essential that we maintain normal occlusion and preserve the masticatory
      function as long as possible to prevent the attenuation of hippocampus, caused by
      occlusal disharmony and reduced mastication. We provide an overview on how
      mastication activates various cortical areas of the brain and how an increase in
      the cerebral blood oxygen level of hippocampus and prefrontal cortex (PFC)
      accentuates the learning and memory process. We also justify why maintaining and
      establishing a normal occlusion is important from neurological point of view.

PMID- 30302136
TI  - Association of feeding behavior with jaw bone metabolism and tongue pressure.
AB  - In recent decades, the eating habits of children and adolescents have undergone
      many changes due to the diversification of lifestyles worldwide. Reduced
      masticatory function in growing animals results in changes in the mandible,
      including a decrease in bone mass. However, the influence of different eating
      behaviors on jaw bone metabolism (e.g., the palatal palate) during the growth
      period is not fully understood. In addition, recent clinical studies reported
      that masticatory performance is positively related to tongue pressure in adults,
      but no consensus has been reached regarding whether tongue pressure is related to
      masticatory performance in children. This review summarizes current findings
      related to these issues, focusing on the influence of different feeding behaviors
      on jaw bone metabolism, including the development of tongue pressure. Consumption
      of a soft diet had a negative impact on jaw bone metabolism in the maxilla and
      mandible of rats; however, mastication of a hard diet recovered the collapsed
      equilibrium of bone turnover caused by a soft diet during growth. Tongue pressure
      is closely associated with an increase in masticatory performance in children.
      Peak maximum tongue pressure is reached earlier in women than in men. Before
      reaching adulthood, women require intervention to increase their peak tongue
      pressure.

PMID- 30302138
TI  - Introduction to Kampo medicine for dental treatment - Oral pharmacotherapy that
      utilizes the advantages of Western and Kampo medicines.
AB  - Kampo medicine is a medical system that has been systematically organized based
      on the reactions of the human body. At present, in Western, herbal medicines
      means the whole herbal product. It is being called Kampo medicine as a medicinal
      drug in Japan. Since 2012, the "National Health Insurance Drug Price Standards
      Related to Dental Treatment" published by the Japan Dental Association have
      included seven Kampo formulations. In 2015, the Japan Dental Association sent a
      "Kampo Education Plan for Dentistry" to all dental universities in Japan.
      Furthermore, the Japanese Society of Oral Therapeutics and Pharmacology compiled
      a summary of "Evidence for Kampo Treatment in the Field of Oral Surgery." In
      addition, the phrase "including wakan-yaku" was included in the draft core model
      curriculum for dental education in 2016. Thus, Kampo medicine is expected to
      rapidly spread to the field of dental care and dental medical education.
      Therefore, the training of dentists with knowledge of both Western and Oriental
      medicine is required for the treatment of oral pain, periodontal disease,
      stomatitis, xerostomia, and other complaints concerning oral health. It is our
      hope that this paper provides a footing for dentists who wish to learn about
      Kampo medicine and incorporate it into clinical practice.

PMID- 30302137
TI  - Structural features, processing mechanism and gene splice variants of dentin
      sialophosphoprotein.
AB  - Dentin sialophosphoprotein (DSPP) plays an important role in the formation of
      dentin. Understanding its structure and function would provide important insights
      into the regulation of dentin mineralization. For the past 15 years, we have been
      studying DSPP-derived proteins isolated from pig dentin. Porcine DSPP is
      synthesized and secreted by odontoblasts and processed into three proteins, i.e.,
      dentin sialoprotein (DSP), dentin glycoprotein (DGP), and dentin phosphoprotein
      (DPP), by bone morphogenetic protein 1 and matrix metalloproteinase-20 and -2.
      DSP is a proteoglycan that forms covalent dimers, DGP is a phosphorylated
      glycoprotein, and DPP is a highly phosphorylated intrinsically disordered protein
      with genetic polymorphisms. Furthermore, DPP is not detected in dental pulp. This
      is possibly due to the existence of two mRNA variants of the DSPP gene: one that
      encodes the DSP region alone and another that encodes full-length DSPP. The mRNA
      variant encoding DSP alone is expressed in dental pulp and odontoblasts, but the
      variant encoding full-length DSPP is predominantly expressed in odontoblasts and
      barely in dental pulp.

PMID- 30302139
TI  - Lateral laparoscopic adrenalectomy in patients with previous abdominal surgery -
      single-center experience.
AB  - Introduction: Lateral transabdominal adrenalectomy (LTA) is the most common
      minimally invasive technique used to treat patients with adrenal tumors. Aim: To
      analyze intra-operative and post-operative complications and reasons for
      conversion to open surgery in patients who underwent LTA and had previous
      abdominal surgery. Material and methods: Five hundred and nineteen patients
      underwent LTA in our center between 2005 and 2016. We identified a study group of
      150 patients, with previous abdominal surgery. We analyzed the frequency of intra
      operative and post-operative complications and the reasons for conversion from
      laparoscopic to open adrenalectomy. Results: The patients' mean age was 58; they
      underwent LTA due to hormonally active tumors (n = 79, 53%) and non-functioning
      adrenal tumors (n = 71, 47%). The size of adrenal lesions ranged from 20 mm to 90
      mm. Seventy-eight (52%) adrenal lesions were found in the right adrenal gland,
      and 72 (48%) lesions in the left adrenal gland. The mean operating time was 130
      min. The mean stay in hospital was five days. The intra-operative complications
      included blood pressure fluctuations (n = 32), abnormal vascular supply of the
      adrenal glands causing difficulties with dissections (n = 3), and respiratory
      problems (n = 1). Two (1.3%) patients had post-operative bleeding at the site of
      removed adrenal glands; 1 patient had an exacerbation of asthma postoperatively.
      Of the 150 patients analyzed, 3 (2%) required conversion to open adrenalectomy.
      The conversions were not caused by abdominal adhesions. Conclusions: Lateral
      transabdominal adrenalectomy is feasible and safe in patients with previous
      abdominal surgery. In our study, conversion from laparoscopic to open
      adrenalectomy was not caused by abdominal adhesions.

PMID- 30302140
TI  - Adrenal cysts - optimal laparoscopic treatment.
AB  - Introduction: Adrenal cysts develop in up to about 0.2% of the overall
      population. They may account for up to 11% of all pathologies of adrenal glands.
      Aim: Is laparoscopic resection of adrenal cysts a method for the treatment of
      these pathologies? Material and methods: In the years 2010-2017, a total of 27
      patients underwent surgery due to adrenal cysts; those included 18 (66.7%) women
      and 9 (33.3%) men aged 29 to 84 years (mean age: 42.7). Cyst diameter ranged from
      55 to 130 mm. After exclusion of hormonal hyperactivity, parasitic cysts, or, to
      the best possible extent, cancer lesions, patients were qualified for adrenal
      sparing laparoscopic surgery. Results: All patients were subjected to
      laparoscopic surgery. Cystic wall resection was performed in 15 (55.6%) patients
      while adrenalectomy was performed in the remaining 12 (44.4%) patients. The
      decision regarding the extent of the surgery was made intraoperatively.
      Histopathological assessment revealed pathological adrenal lesions in as few as 3
      (11.1%) patients, with the rest of the study population, i.e. 24 (88.9%),
      presenting with normal adrenal tissue. Conclusions: Laparoscopic resection of
      adrenal cysts appears to be recommendable as a method for the treatment of these
      pathologies. It is simpler than adrenalectomy and associated with low risk of any
      pathological lesion remaining within the adrenal gland following careful
      intraoperative assessment by an experienced surgeon.

PMID- 30302141
TI  - Short- and long-term results of laparoscopic adrenalectomy for Conn's syndrome.
AB  - Introduction: The primary treatment of Conn's syndrome (CS) is laparoscopic
      adrenalectomy and aims to normalize arterial blood pressure and biochemical
      parameters. Aim: To analyse short- and long-term results of laparoscopic
      adrenalectomy for Conn's syndrome (CS). Material and methods: The analysis
      included 44 consecutive patients, who underwent laparoscopic adrenalectomy
      between 2004 and 2015 for CS. We analysed short- and long-terms results of
      operations. All patients were followed up 6 and 24 months after surgery to
      determine changes in the biochemical parameters, and clinical regression of
      arterial hypertension. We also evaluated the aldosteronoma resolution score (ARS)
      in predicting the resolution of hypertension. Results: No conversions were
      needed. Complications occurred in 5 (11.4%) patients. Preoperative hypokalaemia
      and hypernatraemia were present in 83.4% and 15.8% of patients, respectively.
      After surgery, both hypokalaemia and hypernatraemia resolved in all patients. At
      the follow-up 6 months after the surgery, only 11.3% of patients had complete
      remission (CR) of hypertension. In 43.2% of cases we observed partial remission
      (PR). After 24 months CR was found in 13.6% of patients, 45.5% patients fulfilled
      criteria for PR, and 29.5% of patients changed the group of remission comparison
      to the first follow-up visit. Only 50% of patients with an ARS of 4 or 5 points
      achieved CR 6 months after surgery. Conclusions: Laparoscopic adrenalectomy is a
      safe method of treatment for CS. Although it effectively eliminates electrolyte
      imbalance, it does not allow for the CR of hypertension in the majority of
      patients, especially in the elderly group. We did not find ARS to be an effective
      tool in predicting postoperative resolution of hypertension.

PMID- 30302142
TI  - Neovascularization after ischemic conditioning of the stomach and the influence
      of follow-up neoadjuvant chemotherapy thereon.
AB  - Introduction: Esophagectomy and reconstruction remain the optimal treatment for
      patients with resectable esophageal cancer. Neovascularization after ischemic
      conditioning of the stomach before esophagectomy is a laparoscopic procedure
      which may potentially reduce gastric conduit ischemia. Aim: To investigate the
      influence of ischemic conditioning on neovascularization along the greater
      curvature of the stomach and to explore the effect of neoadjuvant chemotherapy on
      neovascularization after ischemic conditioning. Material and methods: Staging
      laparoscopy was performed before the main resection procedure; during this
      procedure ischemic conditioning was performed. Samples taken from the human
      stomach were divided into 3 groups: group A - patients after ischemic
      conditioning with a delay of 30-45 days after left gastric artery (LGA) ligation
      (n = 4); group B - patients who were undergoing neoadjuvant chemotherapy with a
      delay of 90-140 days after left gastric artery ligation (n = 4); and control
      group C - patients without ischemic conditioning (n = 7). Results: After ischemic
      conditioning with a delay of 30-45 days, the count of neovessels along the
      greater curvature of the stomach increased from 5.4 +/-0.7 in the control group
      to 17.5 +/-0.9 in a low-power field of view (LPF) in group A and increased still
      further on average to 19.8 +/-10.4 in group B. Conclusions: Left gastric artery
      ligation only is a sufficient procedure for ischemic conditioning of the stomach.
      Neovascularization along the greater curvature is a continuous process that
      depends on delay time. Neoadjuvant therapy has no influence on the effect of
      neovascularization.

PMID- 30302143
TI  - Defunctioning ileostomy and mechanical bowel preparation may contribute to
      development of low anterior resection syndrome.
AB  - Introduction: Laparoscopic surgery is an approved technique in colorectal cancer
      treatment. Functional and quality-of-life studies have revealed significant
      changes in faecal continence. Aim: To assess the incidence and risk factors of
      low anterior resection syndrome (LARS) in patients undergoing rectal resections
      for cancer. Material and methods: We enrolled patients undergoing rectal
      resections in a general surgery department of a university hospital. The primary
      outcomes were the Jorge-Wexner scale and the LARS score 6 months after the end of
      treatment. The secondary outcomes were the risk factors for LARS development.
      Results: Fifty-six patients were included; 15 (26%) developed major LARS and 10
      (18%) had minor LARS at 6 months. In univariate analysis the risk factors were:
      preoperative radiotherapy (p < 0.001, OR = 11.9, 95% CI: 2.98-47.48); shorter
      distance of the tumour from the anal verge (p = 0.001, OR = 0.69, 95% CI: 0.55
      0.86); bowel preparation (p = 0.01, OR = 6.27, 95% CI: 1.51-26.07); low anterior
      rectal resection (p = 0.01, OR = 17.07, 95% CI: 1.86-156.83); and protective
      ileostomy (p = 0.001, OR = 15.97, 95% CI: 4.07-61.92). The risk factors for a
      higher Jorge-Wexner score in univariate analysis were greater diameter of tumour
      (p = 0.035), radiotherapy (p = 0.001), shorter distance from the anal verge (p =
      0.002), bowel preparation (p = 0.042), low anterior rectal (LAR) (p = 0.01),
      ileostomy (p = 0.001), perioperative complications (p = 0.032), and readmission
      within 30 days (p = 0.034). In the multivariate analysis, readmissions and
      perioperative complications were significant. Conclusions: In addition to
      typically described risk factors, two new ones have been identified. Mechanical
      bowel preparation and defunctioning ileostomy may also contribute to LARS
      development. However, due to the limitations of this study our observations
      require further confirmation in future trials.

PMID- 30302144
TI  - Use of inflammatory markers in the early detection of infectious complications
      after laparoscopic colorectal cancer surgery with the ERAS protocol.
AB  - Introduction: Thanks to laparoscopy and enhanced recovery protocols (ERAS) it is
      possible to shorten hospitalization. Therefore, it seems reasonable to search for
      new early markers of infectious complications in order to select patients who are
      prone to development of complications. Aim: To assess the usefulness of serum
      levels of C-reactive protein, interleukin-6 and procalcitonin as early indicators
      of infectious complications in patients after laparoscopic colorectal surgery
      with ERAS. Material and methods: The prospective analysis included consecutive
      patients who underwent laparoscopic colorectal cancer resection. The following
      parameters were included in the analysis: C-reactive protein (CRP), interleukin 6
      (IL-6) and procalcitonin measured on postoperative days (PODs) 1, 2, 3. Patients
      were divided into two groups: uncomplicated (group 1) and complicated (group 2).
      The difference in levels of the markers and the dynamics of changes observed in
      both groups were analyzed. Results: Group 1 comprised 34 patients, and group 2
      consisted of 17 patients. A significant increase of both absolute values and
      delta increments on all postoperative days was noted. ROC curve analysis showed
      that the best cut-off values indicating an infectious process were: CRP 129 mg/l
      on POD3 (92% sensitivity/80% specificity), IL-6 of 78 pg/ml on POD2 (91%
      sensitivity/97% specificity) and PCT 0.24 ng/ml on POD3 (93% sensitivity/68%
      specificity). Conclusions: Our study showed that regular measurement of all
      analyzed markers in the early postoperative days may be beneficial in the
      detection of postoperative infectious complications. Further studies are needed
      to fully assess the role of routine biochemical measurements in the postoperative
      period after laparoscopic surgery with the ERAS protocol.

PMID- 30302145
TI  - Postoperative complications are associated with worse survival after laparoscopic
      surgery for non-metastatic colorectal cancer - interim analysis of 3-year overall
      survival.
AB  - Introduction: Postoperative morbidity after colorectal resections for cancer
      remains a significant problem. Data on the influence of complications on survival
      after laparoscopic colorectal resection are still limited. Aim: To analyze the
      impact of postoperative complications on long-term survival after radical
      laparoscopic resection for colorectal cancer. Material and methods: Two hundred
      and sixty-five consecutive non-metastatic colorectal cancer patients undergoing
      laparoscopic colorectal resection for cancer were included in the analysis. The
      entire study group was divided into two subgroups based on the occurrence of
      postoperative complications. Group 1 included patients without postoperative
      morbidity and group 2 included patients with complications. The primary outcome
      was overall survival. Results: Median follow-up was 45 (IQR: 34-55) months. Group
      1 consisted of 187 (70.5%) patients and group 2 comprised 78 (29.5%) patients.
      Studied groups were comparable in terms of sex, age, body mass index, ASA class,
      cancer staging, localization of the tumor and operative time. Patients in group 1
      had significantly better overall 3-year survival compared to those with
      complications (84.9% vs. 69.8%, p = 0.022). Kaplan-Meier curves showed
      significantly improved survival rates in patients without complications compared
      with complicated cases. The Cox proportional multivariate model showed that
      postoperative complications (HR = 2.83; 95% CI: 1.35-5.92; p = 0.0058) and AJCC
      III (HR = 3.17; 95% CI: 1.52-6.6; p = 0.0021) were independent predictors of
      worse survival after laparoscopic colorectal cancer surgery. Conclusions: Our
      analysis of interim results after 3 years confirms that complications after
      laparoscopic colorectal cancer surgery have an impact on survival. For this
      reason, these patients should be carefully monitored after surgery aiming at
      early detection of recurrence.

PMID- 30302146
TI  - Comparison of resection site of standardized laparoscopic hepatic tumor
      resection.
AB  - Introduction: The degree of difficulty in laparoscopic hepatic resection (LHR)
      was higher in tumors involving the suprahepatic segments than other sites.
      However, thanks to surgical instruments and procedures being improved and
      standardized, LHR can be performed safely in all regions. Aim: We report our
      standardized surgical techniques and outcomes in a series of patients undergoing
      LHR in our hospital and analyze the surgical outcomes, particularly with regard
      to the site of resection. Material and methods: We retrospectively analyzed data
      from 238 patients who underwent standardized laparoscopic partial hepatic
      resection between 2010 and 2017. In standardized LHR, the operator formed a
      triangle with the laparoscope in the center, maintaining a co-axial position by
      changing the port where the laparoscope was inserted. Results: Operative time for
      the resection of tumors of the right hepatic lobe was 202 +/-92 min and 140 +/
      104 min for tumors of the left hepatic lobe (p = 0.0024); intraoperative blood
      loss was 80 +/-170 ml and 19 +/-127 ml, respectively (p = 0.0016). No differences
      were found in the surgical outcomes between the various segments of the right
      hepatic lobe. In the left hepatic lobe, operative time was significantly shorter
      with laparoscopic tumor resection in segment III (p = 0.0023). Conclusions:
      During standardized LHR, a better field of vision with the greater ease can be
      established during resection of the left hepatic lobe compared to that of the
      right hepatic lobe. Nonetheless, LHR of the right lobe can be performed safely
      using various surgical instruments and techniques.

PMID- 30302147
TI  - Randomized trial of umbilical incisional hernia in high-risk patients: extraction
      of gallbladder through subxiphoid port vs. umbilical port after laparoscopic
      cholecystectomy.
AB  - Introduction: Trocar site incisional hernia (TSIH) is one of the most common
      complications of laparoscopic surgery. Using the umbilical port as a common hole
      for removing the gallbladder in laparoscopic cholecystectomy is more likely to
      lead to TSIH than other ports. Thus, extracting the gallbladder through other
      ports may reduce the incidence of TSIH. Aim: To ascertain whether extraction of
      the gallbladder through the subxiphoid port is more beneficial for reducing
      umbilical incisional hernia than the umbilical port. Material and methods: From
      April 2014 to March 2017, a randomized clinical trial was conducted among
      patients with high risk of incisional hernia and accepted for three-port
      laparoscopic cholecystectomy (TLC) in our department. 182 patients with
      indications of cholecystectomy were allocated randomly to group A (subxiphoid
      port) and group B (umbilical port). Data collection was carried out on operative
      time, postoperative pain, hospital stay, wound infection and TSIH in the early
      postoperative course, and at 1, 10, and 24 months after surgery. Results: The
      incidence of TSIH in group A was lower than that in group B (4.9% vs. 14.6%; odds
      ratio = 8.02; 95% CI: 2.15-47.6; p < 0.001). The mean operative time of group A
      was significantly shorter than that of group B (35 +/-15.16 min vs. 42 +/-14.58
      min, p < 0.01). There was no significant difference in wound infection rate
      between group A and group B (p = 0.068). The data of hospital stay (p = 0.428)
      and postoperative pain (p = 0.349) of all analyzed patients were similar in the
      two groups. Conclusions: Extraction of the gallbladder through the subxiphoid
      port can reduce umbilical incisional hernia in high-risk patients effectively.

PMID- 30302148
TI  - The Surgical Apgar Score and frailty as outcome predictors in short- and long
      term evaluation of fit and frail older patients undergoing elective laparoscopic
      cholecystectomy - a prospective cohort study.
AB  - Introduction: Frailty increases the risk of poor surgical outcomes in the older
      population. Some intraoperative factors may also influence the final result and
      can be evaluated. The Surgical Apgar Score (SAS) is a simple system predicting
      postoperative mortality and morbidity. However, the utility of the SAS remains
      unknown in fit and frail older patients undergoing elective laparoscopic
      cholecystectomy due to benign gallbladder diseases. Aim: To evaluate the
      usefulness of the SAS in predicting 30-day morbidity and 1-year mortality in
      older fit and frail patients undergoing elective laparoscopic cholecystectomy.
      Material and methods: Consecutive patients (>= 70 years) were enrolled in the
      prospective study. The Comprehensive Geriatric Assessment (CGA) was used to
      diagnose frailty. Logistic regression was conducted to investigate the
      association between the scores and the outcomes. Results: The study included 144
      consecutive older patients with a median age of 76 (range: 70-91) years. The
      prevalence of frailty was 44.4%. The 30-day mortality and morbidity were 0% and
      11.8%, respectively. The 1-year mortality was 6.3% and 7 out of 9 occurred in the
      frail group. SAS < 7 points was identified as an independent predictor of 30-day
      postoperative morbidity (OR = 5.1; 95% CI: 1.5-18.1). Age > 85 years (OR = 1.9;
      95% CI: 1.2-16.4) and frailty (OR = 3.4; 95% CI: 1.1-19.3) were predictors of 1
      year mortality. Conclusions: Laparoscopic cholecystectomy can be safely performed
      in older fit and frail patients. The SAS, not age, turned out to be the most
      important predictor of 30-day morbidity. Frailty and age > 85 years were
      predictors of 1-year mortality. Older patients with SAS < 7 points should be
      followed meticulously in order to diagnose and treat potential complications
      early on.

PMID- 30302149
TI  - A promising technique for easier single incision laparoscopic cholecystectomy:
      needle grasper traction of gallbladder.
AB  - Introduction: Laparoscopic cholecystectomy (LC) is the primary treatment method
      for benign gallbladder diseases. Single incision laparoscopic cholecystectomy
      (SILC) was reported to be superior in terms of work return, cosmetic results, and
      post-operative pain, but limited maneuver capacity and overlapping of hand tools
      are technical difficulties associated with SILC that endanger patient safety.
      Aim: To perform SILC using a needle grasper for gallbladder traction, thus
      simplifying the dissection of Calot's triangle. Material and methods: The files
      of patients who underwent elective LC for gallbladder stone and polyps in general
      surgery clinics between December 2013 and December 2014 were analyzed
      retrospectively. The patients were divided into two groups: needle-grasper
      assisted SILC (nSILC) and conventional laparoscopic cholecystectomy (CLC). Age,
      gender, height, weight, body mass index, visual analog scale (VAS) scores, ASA
      score, duration of operation, duration of post-operative hospital stay,
      complications, drain use, conversion to open and conventional technique, and oral
      feeding beginning time were analyzed. Results: There were no per-operative or
      post-operative complications in either of the groups, and no significant
      differences were found between the groups in terms of complications. The mean
      duration of the operation was significantly longer in the nSILC group. There was
      no difference between the groups in terms of hospital stay. The mean visual
      analogue scale (VAS) scores in conventional nSILC were significantly lower for
      all hours. The patient satisfaction in terms of cosmetic results was better in
      the nSILC group. Conclusions: Needle-grasper-assisted SILC reduces the number of
      tools that need to be held by surgeons; it also provides safe dissection, better
      cosmetic results, and less post-operative pain in elective cases.

PMID- 30302150
TI  - Fasting and postprandial acyl and desacyl ghrelin and the acyl/desacyl ratio in
      obese patients before and after different types of bariatric surgery.
AB  - Introduction: The mechanism underlying beneficial outcomes of bariatric surgery
      still remains unclear. Especially little is known about hormonal and metabolic
      changes induced by the novel bariatric procedure mini gastric bypass (MGB). Aim:
      To evaluate pre- and post-prandial changes in both ghrelin isoforms in obese
      patients without diabetes and cardiovascular complications treated with MGB,
      sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) surgery. Material and
      methods: From 45 patients initially enrolled in the study, 23 persons completed a
      one-year follow-up period. Venous blood for acyl and desacyl ghrelin (AG and DAG)
      as well as other metabolic assays was collected 3 months before and 6 and 12
      months after bariatric surgery (MGB, RYGB, SG) - in the fasting state and 2 h
      after the consumption of a standard 300 kcal-mixed meal (Nutridrink standard,
      Nutricia). Results: AG and DAG levels (both fasting and prandial) as well as
      AG/DAG ratio did not change after 6 and 12 months in MGB and RYGB groups. In the
      SG group we observed a significant decrease in fasting and postprandial DAG
      levels and consecutively an increase in the fasting AG/DAG ratio after 6 and 12
      months. Six months after surgery we observed some differences between
      carbohydrate metabolism measures in the MGB group (lower HbA1c, HOMA-IR and
      fasting insulinaemia) in comparison to the rest of the participants, but 12
      months after each type of surgery body mass index and indices of carbohydrate and
      lipid metabolism did not differ. Conclusions: The results of our study
      demonstrate that all studied bariatric procedures can successfully reduce overall
      body weight and suggest also that the mechanisms of weight loss and improvement
      in carbohydrate and lipid metabolism after all three types of surgery are
      independent of ghrelin and the acyl/desacyl ghrelin ratio.

PMID- 30302151
TI  - Comparative study of video-assisted thoracoscopic surgery versus open thymectomy
      for thymoma and myasthenia gravis.
AB  - Introduction: Thymectomy is the preferred standard treatment in younger non
      thymoma patients with myasthenia gravis as well as in patients with early stage
      thymoma. Total thymectomy by median sternotomy has been the surgical approach
      since resection of the thymus with video-assisted thoracoscopic surgery (VATS).
      Aim: To compare the clinical outcomes of VATS thymectomy with conventional open
      thymectomy for neoplastic and non-neoplastic thymic diseases. Material and
      methods: Forty patients underwent thymectomy between October 2012 and January
      2016. Fifteen patients were male and 25 patients were female. The mean age was
      40.3 +/-17.7 years. Seventeen (55%) patients underwent VATS thymectomy and 23
      (45%) patients underwent an open procedure. We retrospectively reviewed the data
      of the patients and compared these two techniques. Results: The mean tumor size
      was 5.17 +/-3.2 cm in the thymoma group (VATS 2.5 +/-2.4 cm vs. open access 4.7
      +/-3.7 cm). None of the patients experienced a myasthenic crisis. Conversion to
      thoracotomy was required in 1 patient in the VATS group due to bleeding from the
      right internal mammary artery; therefore, the conversion rate was 2.5% among all
      the patients. No mortality occurred in either group. No significant difference
      was found in the perioperative blood loss, operative time or pain visual analogue
      scale scores. On the other hand, regarding postoperative drainage, duration of
      chest tube drainage and length of hospital stay, VATS thymectomy yielded better
      results and the differences were significant. Conclusions: Video-assisted
      thoracoscopic surgery thymectomy can be performed for both neoplastic and non
      neoplastic thymic diseases with minimal morbidity and mortality.

PMID- 30302152
TI  - Minimally invasive repair of pectus carinatum by modification of the Abramson
      technique.
AB  - Introduction: The minimally invasive pectus carinatum surgery described by
      Abramson has been performed in many centers. We modified the "sub-muscular tunnel
      creation" part of the original Abramson technique. Aim: To compare the operative
      time between the original Abramson technique and a lightly modified approach.
      Material and methods: A retrospective review of 84 patients who underwent
      minimally invasive repair of pectus carinatum deformity between July 2008 and
      November 2017 was performed. We applied two different techniques, the original
      Abramson technique and the modified technique. Sixty-eight patients - 49 (72%)
      males and 19 (28%) females - underwent minimally invasive repair of a pectus
      carinatum deformity as described by Abramson (Abramson group). Sixteen patients -
      13 (81%) males and 3 (19%) females - were operated on by our modified Abramson
      technique at our institution (Modified group). Results: Eighty-four patients were
      included in this study: 68 patients from the Abramson group and 16 patients from
      the Modified group. There was no significant difference between the groups with
      respect to preoperative demographic features, including median age and sex.
      Median operative time was significantly shorter in the Modified group than the
      Abramson group (43 min, range: 32-54 min) in the Modified group vs. 30 min
      (range: 20-35 min) in the Abramson group (p < 0.001). Conclusions: This article
      describes a modification of a surgical technique that is safely and easily used
      in minimally invasive correction of pectus carinatum deformities, with minimal
      complications, high satisfaction rates and shorter operative time.

PMID- 30302153
TI  - Minimally invasive injection laryngoplasty in the management of unilateral vocal
      cord paralysis after video-assisted mediastinal lymph adenectomy.
AB  - Introduction: Video-assisted mediastinal lymphadenectomy (VAMLA) is a valuable
      tool for invasive staging of the mediastinum. Unilateral vocal cord paralysis
      (UVCP) may occur in patients following VAMLA and may result in secretion
      retention within the lungs, atelectasis and associated infectious situations such
      as pneumonia. Minimally invasive injection laryngoplasty (ILP) is the treatment
      of choice in UVCP. Aim: To evaluate the efficacy and success of acute minimally
      invasive injection laryngoplasty for patients with UVCP following VAMLA. Material
      and methods: Patients with the symptom of dysphonia following VAMLA were
      reviewed. All of the patients had UVCP according to the video laryngoscopy
      examination and had symptoms of aspiration and ineffective coughing. The Voice
      Handicap Index (VHI) questionnaire and maximum phonation time (MPT) were
      measured. Minimally invasive ILP was performed under general anesthesia with 1 cm
      of hyaluronic acid. Results: There were 525 consecutive non-small cell lung
      cancer (NSCLC) patients who underwent VAMLA. Five (0.95%) of the patients had
      UVCP and were suffering from aspiration during oral intake and ineffective
      coughing reflex. Maximum phonation time (MFT) was measured before and after ILP,
      and the results were 7.1 +/-1.6 and 11.1 +/-2.3 s, respectively (p < 001). The
      Voice Handicap Index-10 (VHI-10) score was 30.4 +/-4.7 and 13.4 +/-3.5 (p <
      0.01), respectively. Patients underwent surgical lung resection. There was no
      morbidity or mortality. Conclusions: Unilateral vocal cord paralysis may occur as
      a complication of VAMLA. ILP may be an active tool for treating UVCP before
      anatomical lung resection to avoid potential morbidities. Successful management
      of this complication with multidisciplinary team work may encourage the use of
      VAMLA more frequently.

PMID- 30302154
TI  - An investigation on endoscopic laryngopharyngeal surgery and related outcomes.
AB  - Introduction: Robotic surgery is used in Europe and the US for
      oropharyngeal/hypopharyngeal cancers. Although robots can successfully perform
      procedures that are too delicate for surgeons and quickly learn accurate
      techniques, robotic surgery is not still authorized for the craniocervical region
      in Japan. In Japan, endoscopic laryngopharyngeal surgery (ELPS) is widely
      performed. Because oropharyngeal/hypopharyngeal cancer can be resected at an
      early stage, we have contributed to an improvement in the survival rate. Aim: To
      analyze clinical outcomes and risk factors of postoperative cervical lymph node
      metastases after ELPS. Material and methods: Fifty-two patients with 71
      superficial oropharyngeal/hypopharyngeal cancers were included. A Sato-type
      arcuation laryngoscope was inserted, and oropharyngeal and hypopharyngeal fields
      were secured. We have recently been performing head and neck surgery using only a
      flexible endoscope because gastroscopy and arcuation-type forceps interfere with
      each other. Results: The 5-year survival rate was 95.2%. The risk factors of
      lymph node metastases were examined. The depth of the tumor significantly
      affected lymph node metastases. Conclusions: With a favorable 5-year survival
      rate and low functional impairment, ELPS is an extremely effective form of
      treatment. It can provide a clear field of view in the hypopharynx and has a low
      cost; hence, it should be further developed as a treatment method.

PMID- 30302155
TI  - Comparison of outcomes of conventional transcanalicular laser
      dacryocystorhinostomy and modified transcanalicular laser dacryocystorhinostomy.
AB  - Introduction: Transcanalicular laser DCR (TL-DCR) approaches have been developed
      for the formation of a fistula between the nasal cavity and the lacrimal sac to
      ensure the continuity of the lacrimal drainage system over the years. However,
      the success rate of TL-DCR has varied widely. Aim: To evaluate and compare the
      success rates of conventional transcanalicular multidiode laser
      dacryocystorhinostomy and modified transcanalicular multidiode laser
      dacryocystorhinostomy. Material and methods: Ninety-one eyes of 91 adult patients
      admitted with epiphora and diagnosed with chronic dacryocystitis were included in
      the study. The participants were divided into two groups. Group 1 consisted of 55
      patients who were treated with conventional transcanalicular laser
      dacryocystorhinostomy. Group 2 consisted of 36 patients to whom the same surgical
      procedure was applied with the difference of nasal mucosa excision prior to laser
      osteotomy. The groups' intraoperative surgical ostium size, perioperative and
      postoperative complications, operative times and success rates were compared.
      Results: The mean follow-up periods for each group were 8.88 +/-2.99 months and
      10.28 +/-4.47 months, respectively (p = 0.077). Intraoperative mean surgical
      ostium sizes were 31.85 +/-14.98 mm2 and 42.25 +/-18.09 mm2, respectively (p =
      0.004). The mean operation time in group 1 was significantly shorter compared to
      group 2 (18.55 +/-4.05 min and 24.44 +/-3.18 min, respectively, p = 0.0001). The
      overall success rate was 65.45% in group 1 and 75.00% in group 2 (p = 0.335).
      Conclusions: Although the surgical ostium area was significantly greater in group
      2, there was no significant difference in surgical success and patient
      satisfaction rates between the two groups.

PMID- 30302156
TI  - Single-anastomosis duodeno-ileal - new revision procedure in a patient with
      insufficient weight loss after sleeve gastrectomy.
AB  - Laparoscopic sleeve gastrectomy (LSG) is one of the most popular and effective
      bariatric surgical procedures worldwide. The effect of LSG is mostly dependent on
      the restrictive mechanism, which makes it more vulnerable to failure. Failing of
      bariatric procedure is not uncommon and occurs in 6% to 23%. In case of weight
      loss failure, there are no hard recommendations on the choice of the redo
      procedure. One of the most novel options, introduced in 2007, relatively simple
      to perform following LSG is single-anastomosis duodenoileal bypass. Herein we
      describe surgical technique and history of a patient with inadequate weight loss
      after laparoscopic sleeve gastrectomy, who underwent single-anastomosis
      duodenoileal bypass.

PMID- 30302157
TI  - Minimally invasive techniques and indocyanine angiography in anterior abdominal
      wall reconstruction after multiple laparotomies.
AB  - Anterior abdominal wall reconstruction surgery in patients who have undergone
      multiple laparotomies is associated with a high risk of complications. For this
      reason, minimally invasive surgery techniques are used to avoid abdominal
      compartment syndrome, to enhance wound healing and to reduce postoperative pain
      and blood loss. This paper presents a case of a patient who was admitted to the
      Department of General Surgery in Puck Hospital as a result of extensive anterior
      abdominal wall deformation with an end descending colostomy. A single-stage
      procedure was performed: specifically, digestive tract reconstruction followed by
      anterior abdominal wall reconstruction using intraoperative angiography of
      indocyanine green in infrared light.

PMID- 30302158
TI  - Endoscopic removal of an impacted wooden toothpick in the wall of the sigmoid
      colon.
AB  - Most ingested foreign bodies usually pass through the gastrointestinal tract
      without any complications. Sharp foreign bodies such as a wooden toothpick may
      cause severe complications, leading to an acute abdomen. They may also cause
      mild, non-specific gastrointestinal symptoms without significant findings. We
      describe a case of a 60-year-old man initially diagnosed with a foreign body
      impacted into the wall of the rectosigmoid junction upon screening colonoscopy.
      Incidentally, ingestion of the wooden toothpick 6 months before admission and the
      presence of recurrent fever and lower abdominal pain were confirmed in the
      patient's history. Our video case study demonstrates the successful endoscopic
      removal of the wooden toothpick impacted into the colon wall.

PMID- 30302159
TI  - Lateral frontoethmoidal cell obstructing frontal sinus drainage pathway - report
      of six cases.
AB  - : The European Anatomical Position Paper on the Anatomical Terminology of the
      Internal Nose and Paranasal Sinuses distinguishes anterior, posterior, medial and
      lateral frontoethmoidal cells. The lateral cells have not been characterized yet.
      Other classifications (Lee and Kuhn, International Frontal Sinus Anatomy
      Classification) neglect them. The aim of this study is to describe lateral
      frontoethmoidal cells in rhinosinusitis patients. METHOD: Analysis of medical
      records and computed tomography (CT) examinations using multiplanar
      reconstruction with adjustable planes. The lateral cell extending between the
      frontal beak and the skull base pushing the frontal sinus drainage pathway
      medially/anteromedially was identified in 6 patients. These cells could not be
      classified as anterior, posterior or medial according to existing
      classifications. Four patients were operated on previously due to sinonasal
      symptoms. The lateral frontoethmoidal cell is an underestimated anatomical
      variation that may contribute to the persistence of inflammatory disease and can
      be easily overlooked preoperatively.

PMID- 30302160
TI  - Diagnostic and therapeutic recommendations for chronic pancreatitis.
      Recommendations of the Working Group of the Polish Society of Gastroenterology
      and the Polish Pancreas Club.
AB  - This article describes the latest diagnostic and therapeutic recommendations in
      chronic pancreatitis, developed by the Working Group of the Polish Society of
      Gastroenterology and the Polish Pancreas Club. The recommendations refer to the
      diagnosis of chronic pancreatitis, autoimmune pancreatitis, conservative
      management, treatment of pain, and exocrine and endocrine pancreatic
      insufficiency, treatment of chronic pancreatitis by endoscopic and surgical
      methods, and oncological surveillance of chronic pancreatitis. This paper refers
      to the Polish recommendations published in 2011, which have been updated and
      supplemented. All recommendations were voted by experts of the Polish Society of
      Gastroenterology and the Polish Pancreas Club, who evaluated them each time on a
      five-degree scale, where I meant full acceptance, II - acceptance with some
      reservation, III - acceptance with serious reservation, IV - rejection with some
      reservation and V - full rejection. The results of the voting, together with a
      brief commentary, have been included with each recommendation put to the vote. In
      addition, the expert group assessed the value of clinical studies on which the
      statements are based, on a scale where A means high (based on meta-analyses and
      randomised clinical trials), B means medium (based on clinical trials and
      observational studies), and C means low (based mainly on expert opinion).

PMID- 30302161
TI  - Morphology of Helicobacter pylori as a result of peptidoglycan and cytoskeleton
      rearrangements.
AB  - Helicobacter pylori is a Gram-negative, microaerophilic bacterium colonising the
      gastric mucosa. Normally, this bacterium has a spiral shape, which is crucial for
      proper colonisation of the stomach and cork-screwing penetration of dense mucin
      covering this organ. However, H. pylori may also form curved/straight rods,
      filamentous forms and coccoid forms. This morphological variability affects
      nutrient transport and respiration processes, as well as motility, the ability to
      form aggregates/biofilms, and resistance to adverse environmental factors. For
      this reason, a more accurate understanding of the molecular determinants that
      control the morphology of H. pylori seems to be crucial in increasing the
      effectiveness of antibacterial therapies directed against this microorganism.
      This article focuses on the molecular factors responsible for peptidoglycan and
      cytoskeleton rearrangements affecting H. pylori morphology and survivability. In
      addition, the existence of proteins associated with modifications of H. pylori
      morphology as potential targets in therapies reducing the virulence of this
      bacterium has been suggested.

PMID- 30302162
TI  - Carcinoid tumour of the oesophagus: a systematic review.
AB  - Introduction: Knowledge about oesophageal carcinoids is based primarily on case
      reports, and therefore information about them is incomplete. Aim: To collect
      information on oesophageal carcinoid tumours in a systematic review study.
      Material and methods: Databases including PubMed, Scopus, and Web of Science were
      searched for the characteristics of oesophageal carcinoid tumour. Studies
      included original articles, case series, or case reports, reporting at least one
      of the characteristics of benign carcinoid tumour or carcinoid tumour. Results:
      Out of 670 studies searched, after evaluation and excluding non-relevant studies,
      14 studies were included and analysed in the systematic review. These studies
      included 19 patients with carcinoid tumour of whom 57.9% were males with a mean
      age of 55.5 years. Dysphagia and weight loss were the most prevalent symptoms and
      signs in the patients. Lower oesophagus was the most prevalent site of tumour.
      Conclusions: This meta-analysis showed that the mean age at diagnosis of
      oesophageal carcinoid was around 55 years, with 1.4 times greater prevalence
      among males, and located mainly in the distal oesophagus. The mean tumour size
      was 2.4 cm. The main symptoms and signs of this disease were dysphagia, weight
      loss, and reflux. The tumour behaviour was mainly non-aggressive except for cases
      associated with adenocarcinoma.

PMID- 30302163
TI  - Diagnosis and treatment of early gastric cancer: experience of one center.
AB  - Introduction: Gastric cancer is one of the most common malignant neoplasms in the
      world. Currently it constitutes the third cause of death among all malignancies.
      New endoscopic techniques have a potential to improve treatment results due to
      more frequent detection of early gastric cancer. Aim: To summarize our experience
      in diagnosis and treatment of early gastric cancer patients. Material and
      methods: We analyzed the results of endoscopic examination, histopathological
      findings and treatment methods in 16 patients who were diagnosed with early
      gastric cancer in the Endoscopy Unit of the Oncology Center in Bydgoszcz between
      2014 and 2016. Results: Between 2014 and 2016 sixteen patients, 12 (75.0%) male
      and 4 (25.0%) female, were diagnosed with early gastric cancer. The average age
      of patients was 65.5 years. Surgery qualification concerned mainly G2 and G3
      adenocarcinomas. In 12 (75.0%) patients total gastrectomy was performed, and 1
      patient underwent wedge resection of the prepyloric part of the stomach. In 3
      cases endoscopic submucosal dissection (ESD) was performed. Histopathological
      examination of both biopsy and postoperative material indicated 8 (50.0%) cases
      of intestinal-type adenocarcinoma, 7 (43.75%) cases of diffuse-type
      adenocarcinoma and 1 (6.25%) case of mixed-type adenocarcinoma. During the follow
      up after treatment, none of the patients was diagnosed with local or distant
      recurrence. Conclusions: Accurate examination technique allows for detection of
      early gastric cancer. Selected cases of early gastric cancer may be treated with
      advanced endoscopic techniques.

PMID- 30302164
TI  - Is narrow-band imaging a useful tool in screening colonoscopy performed by an
      experienced endoscopist? A prospective randomised study on 533 patients.
AB  - Introduction: The detection of adenomas is the basic goal for colorectal cancer
      screening programs; therefore, every possibility to improve the adenoma detection
      rate is valuable. Aim: To answer the question of whether narrow-band imaging
      (NBI) can enhance detection quality in screening for colonoscopy. Material and
      methods: A group of 533 patients (202 men: 331 women; average age: 56.1 years)
      included in a colorectal cancer screening program were randomised into two groups
      (NBI n = 266 and white light (WL) n = 267). Five hundred and twenty-seven
      patients were finally included in the assessment. Examinations were performed by
      three experienced colonoscopists. The NBI was used only at the withdrawal of the
      instrument. Results: Comparing WL and NBI colonoscopies, differences in the mean
      number of detected polyps per patient (1.36 +/-2.79 WL vs. 1.65 +/-2.11 NBI; p =
      0.012), polyp detection rate (PDR) (48.5% WL vs. 57.2% NBI; p = 0.049), PDR for
      polyps <= 5 mm (44.7% WL vs. 54% NBI; p = 0.033), and PDR for left-sided polyps
      (43.3% WL vs. 52.7% NBI; p = 0.033) were observed. The difference in adenoma
      detection rate (ADR) as well as in adenomas/patient was not significant. Narrow
      band imaging enhanced significantly one of three operators' ADR (15.6% WL vs.
      25.7% NBI; p = 0.038). Conclusions: It seems that NBI improves only detection of
      hyperplastic polyps, especially those that are diminutive and left-sided.
      However, after analysis of particular endoscopists, it can clearly be seen that
      some of them may benefit from NBI.

PMID- 30302165
TI  - Therapeutic efficacy of amoxicillin and rifaximin in patients with small
      intestinal bacterial overgrowth and Helicobacter pylori infection.
AB  - Introduction: Small intestinal bacterial overgrowth (SIBO) may coexist with
      Helicobacter pylori infection, which can be the cause of chronic gastrointestinal
      complaints. Aim: Evaluation of the therapeutic efficacy of amoxicillin and
      rifaximin in the treatment of these diseases. Material and methods: The lactulose
      hydrogen breath test (LHBT) and the urea breath test (13C-UBT) were performed in
      116 patients. In 62 patients the coexistence of small intestinal bacterial
      overgrowth and H. pylori infection was observed. Then, in group I (n = 30)
      pantoprazole (2 * 40 mg), amoxicillin (2 * 1000 mg) and metronidazole (2 * 500
      mg) and in group II (n = 32) pantoprazole and amoxicillin at the above doses and
      rifaximin (3 * 400 mg) were administered for 10 days. After 6 weeks, both breath
      tests were repeated and the degree of remission of symptoms was measured using a
      10-point visual analog scale (VAS). Results: After the treatment the LHBT index
      decreased in group I from 61.2 +/-19.4 ppm to 22.0 +/-8.2 ppm (p < 0.001) and in
      group II from 59.6 +/-15.5 ppm to 15.2 +/-8.6 ppm (p < 0.001). Eradication of H.
      pylori (13C-UBT below 4.00/00) was achieved in 63.3% of patients in group I and
      59.4% in group II (p > 0.05). The decrease of pain below 3.0 points in the VAS
      was obtained in 64.8% of patients in group I and in 56.2% in group II.
      Conclusions: Combination of amoxicillin and rifaximin may be effective in the
      treatment of patients with small intestinal bacterial overgrowth syndrome and
      concomitant H. pylori infection.

PMID- 30302166
TI  - The prognostic impact of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte
      ratio, and platelet-to-lymphocyte ratio in patients with advanced colorectal
      cancer treated with first-line chemotherapy.
AB  - Introduction: Colorectal cancer is the second most frequently diagnosed
      malignancy and one of the leading causes of cancer-related death in Poland. Many
      reports of different types of cancer have indicated that blood count parameters
      may serve as a source of prognostic or predictive information. Aim: To assess the
      association between these parameters and clinical outcome in patients with
      advanced colorectal cancer. Material and methods: We retrospectively analysed a
      database of 295 patients with advanced colorectal cancer treated with first-line
      palliative chemotherapy at our institution from January 2008 to December 2012.
      Blood-based parameters were measured before the first cycle of treatment.
      Results: The median progression-free survival (PFS) was 6.7 months, and the
      median overall survival was 17.6 months. A high neutrophil-to-lymphocyte ratio
      (NLR) and a high platelet-to-lymphocyte ratio (PLR) were associated with a
      shorter survival (hazard ratio (HR): 1.88, p < 0.0001 for the NLR and HR: 1.39, p
      = 0.0054 for the PLR), but for the PLR, we observed only a not significant trend
      toward a worse PFS (HR = 1.25, p = 0.07 for the PLR and HR = 1.55, p = 0.0004 for
      the NLR). A high lymphocyte-to-monocyte ratio (LMR) was associated with a better
      prognosis (HR = 0.58, p <= 0.0001) and a longer PFS (HR = 0.73, p = 0.011).
      Conclusions: The blood-based parameters are readily available, reliable, and low
      cost biomarkers, which can be easily incorporated into routine practice to
      predict the prognosis in patients with advanced colorectal cancer.

PMID- 30302167
TI  - Update on the effect of age on acute pancreatitis morbidity: a retrospective,
      single-center study.
AB  - Introduction: Acute pancreatitis (AP) is one of the urgent diseases of
      gastroenterology. Due to the growth of the elderly population, the frequency of
      the disease in the elderly population is also increasing. Aim: To evaluate the
      contributing factors of mortality in geriatric patients (age >= 65 years) and non
      geriatric (age < 65 years) patients. Material and methods: We retrospectively
      analyzed data of consecutive patients with AP, in the Adana Numune Education and
      Research Hospital between March 2013 and September 2015. Results: Of the 602
      patients studied, 405 were female and 197 were male and their mean age was 55.2
      +/-19.5 years. The most common etiological factors were biliary stone,
      hyperlipidemia and alcohol, respectively. Two hundred and four patients were in
      the geriatric group and 394 patients were in the non-geriatric group. 84.4% of
      patients had mild AP, and 15.6% of patients had moderate to severe AP according
      to the revised Atlanta classification. 91.7% of non-geriatric patients had mild
      AP while 70.7% of geriatric patients had mild AP (p < 0.001). 29.4% of geriatric
      patients had moderate-to-severe AP while 8.4% of non-geriatric patients had
      moderate-severe AP. Duration of hospital stay was 6.2 +/-3 days and 5.3 +/-2.3
      days in geriatric and non-geriatric groups respectively (p < 0.001). Mortality
      was higher in the geriatric group than the non-geriatric group (9.6% vs. 0.5%,
      respectively) (p < 0.001). Conclusions: Acute pancreatitis in the geriatric
      population shows a more severe course than the non-geriatric population.
      Geriatric patients have longer duration of hospital stay and higher mortality
      than non-geriatric patients.

PMID- 30302168
TI  - Comparison of the effects and side-effects of sedation with propofol versus
      midazolam plus pethidine in patients undergoing endoscopy in Imam Khomeini
      Hospital, Ahvaz.
AB  - Introduction: Gastrointestinal endoscopy is an invasive and diagnostic procedure
      that causes the patients considerable pain, discomfort, and anxiety. Therefore,
      various types of sedation and analgesia techniques have been used during the
      procedure. Aim: To compare the effects and side-effects of sedation with propofol
      versus midazolam plus pethidine in patients undergoing endoscopy. Material and
      methods: This is a randomised controlled double-blind clinical trial study
      conducted on 272 patients undergoing diagnostic and treatment endoscopy and
      colonoscopy in Imam Khomeini Hospital in Ahvaz between 2017 and 2018. The
      patients were randomly assigned to two groups. Patients in the first group (n =
      136) received propofol with midazolam and ketamine, and the second group (n =
      136) received pethidine and midazolam. Study outcome measures included the
      recovery time, patient satisfaction, quality of sedation, and adverse events.
      Results: The occurrence of complications was higher in the propofol group (25%
      vs. 0%; p = 0.0001). No serious adverse events were observed in the study groups.
      Overall patient satisfaction and quality of sedation assessment scores in the
      propofol group were significantly better than those seen in the pethidine
      midazolam group (p = 0.012 and p = 0.001, respectively). Recovery time was
      statistically shorter in the propofol-midazolam group (6.05 +/-1.62 min) compared
      to the pethidine-midazolam group (6.72 +/-2.21 min) (p = 0.006). Conclusions:
      Propofol-midazolam can provide better sedation, patient satisfaction, and
      recovery than pethidine-midazolam during endoscopy. Therefore, it can be
      recommended in patients scheduled for diagnostic and treatment endoscopy.

PMID- 30302169
TI  - Endoscopic findings in patients with familial Mediterranean fever and dyspeptic
      symptoms.
AB  - Aim: The aim of the study was to evaluate the clinical, endoscopic,
      histopathological, laboratory, and imaging findings of patients with familial
      Mediterranean fever (FMF) presenting with dyspeptic symptoms. Material and
      methods: Endoscopy was performed in 28 patients with FMF undergoing colchicine
      therapy, who presented to our hospital between 2012 and 2014 with abdominal pain,
      diarrhoea, and dyspeptic complaints. Upper gastrointestinal system endoscopy was
      performed in all patients; 16 of these underwent colonoscopy. Demographic
      characteristics, clinical and laboratory data, genetic analysis, imaging data,
      and endoscopy and colonoscopy findings were evaluated in all patients. Results:
      Histopathological analysis of biopsy specimens revealed gastrointestinal
      pathology in 21 (75%) patients. Upper endoscopy analysis revealed that 14 (50%)
      patients had antral gastritis (8 Helicobacter pylori (-) antral gastritis and 6
      H. pylori (+) chronic active gastritis) and 2 (7%) cases had giardiasis. Four
      antral gastritis cases had concomitant esophagitis, and 2 patients had widespread
      ulcers in the terminal ileum. The rest had a normal colonic appearance; however,
      three patients with normal colonoscopic findings were found to have chronic
      active colitis on histopathological examination. Conclusions: In this study, most
      patients with FMF presenting with dyspeptic complaints had gastrointestinal
      pathology. Furthermore, there was higher inflammatory bowel disease incidence in
      these patients.

PMID- 30302170
TI  - Safety analysis of endoscopic haemostasis using a high-frequency live tissue
      electric welding device - EKVZ300 PATONMED.
AB  - Introduction: The method of a bipolar high-frequency welding (HFEW) of soft
      living tissues of animals and humans has been used in various areas of surgery.
      However, it has not been utilized in endoscopic gastrointestinal procedures yet.
      HFEW has strong potential to be used in gastrointestinal endoscopic procedures
      due to the competitive cost of generator devices and due to its proven ability to
      coagulate vessels of wide diameter as compared to standard electrocautery
      devices. Aim: To investigate the effectiveness of the endoscopic haemostasis
      using HFEW generator device - 300 PATONMED - in a porcine model of arterial
      gastrointestinal bleeding. Material and methods: A porcine model of arterial
      gastrointestinal bleeding was created. A 300 PATONMED set to the "welding" regime
      and a flexible 7 Fr bipolar coagulation probe with two electrodes on the tip
      fashioned spirally attached to convey energy were tested. Once bleeding from the
      artery had been initiated, the bipolar probe was applied to coagulate the
      bleeding site. Animals were observed for clinical evidence of recurrent bleeding
      and subsequently were euthanised for histological examination. Results: A total
      of 10 experiments were successfully completed. An optimal haemostatic effect was
      achieved with durations of cautery of five to eight seconds in all animals.
      Continuous observation after haemostasis revealed no evidence of re-bleeding. No
      systemic side-effects of the technique were observed. Histological examination
      has shown that the peripheral thermal injury area that surrounded the coagulation
      zone did not spread beyond the mucosal layer in depth and 2 mm in width.
      Conclusions: This animal study provided evidence for the safety of an HFEW in the
      treatment of gastrointestinal bleeding. The advantages of this technology are
      smokeless operative area, no tissue overheating, minimal necrosis and damage to
      surrounding gastric tissue, and the fact that the area of HFEW is confined to the
      area of the electrodes.

PMID- 30302172
TI  - Does a gluten-free diet determine the efficacy of sotagliflozin in patients with
      concomitant type 1 diabetes mellitus and celiac disease?

PMID- 30302171
TI  - Single transluminal gateway transcystic multiple drainage for extensive walled
      off pancreatic necrosis - a single-centre experience.
AB  - Introduction: In last three decades we have observed development in minimally
      invasive techniques in the treatment of walled-off pancreatic necrosis (WOPN).
      Endoscopic treatment of the consequences of acute necrotising pancreatitis is a
      accepted and common minimally invasive method. Aim: Evaluation of the efficiency
      and safety of the innovative endoscopic treatment method (single transluminal
      gateway transcystic multiple drainage - SGTMD) in patients with extensive walled
      off pancreatic necrosis. Material and methods: The retrospective analysis of 114
      consecutive patients with symptomatic WOPN, who were treated endoscopically in
      our medical centre between 2011 and 2016. Results: Single transluminal gateway
      transcystic multiple drainage was performed in 21/114 (18.42%) patients.
      Endoscopic necrosectomy under fluoroscopic guidance was performed in 12/21
      (57.14%) patients. Complications of treatment appeared in 7/21 (33.33%) patients.
      The most common of complication was upper gastrointestinal bleeding treated
      conservatively with packed red blood cells transfusions. There were no deaths.
      Therapeutic success was reached in 20/21 (95.24%) patients. No patient required
      surgery. The medium time of follow-up was 22 months (16-47). During the
      observation the recurrence of pancreatic fluid collection was noticed in 1/21
      (4.76%) patients. Long-term success of endoscopic treatment was achieved in 19/21
      (90.47%) patients. Conclusions: Single transluminal gateway transcystic multiple
      drainage is an effective method of endoscopic treatment for extensive walled-off
      pancreatic necrosis with an acceptable amount of complications. However, the
      method of interventional treatment of pancreatic necrosis should depend not only
      on the location of necrosis, but also on the experience of the medical centre.

PMID- 30302173
TI  - Cholecystectomy after endoscopic retrograde cholangiopancreatography - effect of
      time on treatment outcomes.

PMID- 30302174
TI  - Biological Efficacy of Medicinal Plant Extracts in Preventing Oxidative Damage.

PMID- 30302176
TI  - Religion in medicine.

PMID- 30302175
TI  - DNA Damage: Health and Longevity.

PMID- 30302177
TI  - A comparison of medication adherence between subsidized and self-paying patients
      in Malaysia.
AB  - Background: Limited efforts have been made to evaluate medication adherence among
      subsidized and self-paying patients. Objective: To investigate medication
      adherence among patients with and without medication subsidies and to identify
      factors that may influence patients' adherence to medication. Setting: Government
      healthcare institutions in Kuala Lumpur, Selangor, and Negeri Sembilan and
      private healthcare institutions in Selangor and Negeri Sembilan, Malaysia.
      Methods: This cross-sectional study sampled patients with and without medication
      subsidies (self-paying patients). Only one of the patient's medications was re
      packed into Medication Event Monitoring Systems (MEMS) bottles, which were
      returned after four weeks. Adherence was defined as the dose regimen being
      executed as prescribed on 80% or more of the days. The factors that may influence
      patients' adherence were modelled using binary logistic regression. Main outcome
      measure: Percentage of medication adherence. Results: A total of 97 patients, 50
      subsidized and 47 self-paying, were included in the study. Medication adherence
      was observed in 50% of the subsidized patients and 63.8% of the self-paying
      patients (chi2=1.887, df=1, p=0.219). None of the evaluated variables had a
      significant influence on patients' medication adherence, with the exception of
      attending drug counselling. Patients who attended drug counselling were found to
      be 3.3 times more likely to adhere to medication than those who did not (adjusted
      odds ratio of 3.29, 95% CI was 1.42 to 7.62, p = 0.006). Conclusion: There is no
      significant difference in terms of medication adherence between subsidized and
      self-paying patients. Future studies may wish to consider evaluating modifiable
      risk factors in the examination of non-adherence among subsidized and self-paying
      patients in Malaysia.

PMID- 30302178
TI  - Achieving triple treatment goals in multi-ethnic Asian patients with type 2
      diabetes mellitus in primary care.
AB  - Introduction: Achieving optimal glycated hemoglobin (HbA1c), blood pressure (BP),
      and LDL-Cholesterol (LDL-C) in patients mitigates macro- and micro-vascular
      complications, which is the key treatment goal in managing type 2 diabetes
      mellitus (T2DM). This study aimed to determine the proportion of patients in an
      urban community with T2DM and the above modifiable conditions attaining triple
      vascular treatment goals based on current practice guidelines. Methods: A
      questionnaire was distributed to adult Asian patients with dyslipidemia at two
      primary care clinics (polyclinics) in northeastern Singapore. The demographic and
      clinical data for this sub-population with both T2DM and dyslipidemia were
      collated with laboratory and treatment information retrieved from their
      electronic health records. The combined data was then analyzed to determine the
      proportion of patients who attained triple treatment goals, and logistic
      regression analysis was used to identify factors associated with this outcome.
      Results: 665 eligible patients [60.5% female, 30.5% Chinese, 35% Malays, and
      34.4% Indians] with a mean age of 60.6 years were recruited. Of these patients,
      71% achieved LDL-C <=2.6 mmol/L, 70.4% had BP <l40/90 mmHg, and 40.9% attained
      HbAlc <=7%. Overall, 22% achieved the triple treatment goals for glycemia, BP,
      and LDL-C control. The major determinants were the number of diabetic medications
      and intensity of statin therapy. Conclusion: Eight in ten patients with T2DM
      failed to achieve concurrent glycemic, BP, and LDL-C treatment goals, subjecting
      them to risks of vascular complications. Primary healthcare professionals can
      mitigate these risks by optimizing therapeutic treatment to maximize glycemia,
      dyslipidemia, and BP control.

PMID- 30302179
TI  - Randomized controlled trial on the effect of Al-Quran recitation vs counseling on
      smoking intensity among Muslim men who are trying to quit smoking.
AB  - Introduction: Nicotine cravings and withdrawal symptoms are associated with
      higher rates of relapse. It has been shown that combining behavioral therapy and
      pharmacotherapy leads to a higher long-term abstinence rate in those who quit
      smoking. Al-Quran recitation has been proven to reduce anxiety among athletes
      before tournaments and pulse and heart rates among patients awaiting cardiac
      operations. As most of the patients who wish to stop smoking experience high
      anxiety states, we postulate that Al-Quran recitation will also able to reduce
      craving among smokers attempting to quit smoking. Methods: Fifty smokers from an
      outpatient clinic were randomly assigned to control and intervention groups. They
      were taught different ways of coping with smoking urges, i.e., counseling using
      the 12'M' method (control group) versus Al-Quran recitation (intervention group).
      They met for four consecutive weeks of counselling and to fill out a withdrawal
      scale. Carbon monoxide (CO) levels were tested at baseline and at week 4. At week
      12, the number of cigarettes smoked was measured again. The decrease in the
      number of cigarettes considered to be clinically significant for the calculation
      of sample size was based on expert opinion. Results: The reduction in the number
      of cigarettes smoked was 7 cigarettes in the counselling group and 9 cigarettes
      in Al-Quran recitation group over 12 weeks duration. There was a statistically
      significant difference in the number of cigarettes smoked between the groups.
      There was also a statistically significant difference in the change in cravings
      between the groups at week 4 (p-value = 0.005). However, the difference in the
      changes in CO levels between the two groups was not statistically significant.
      Conclusion: Al-Quran recitation produced a statistically significant reduction in
      the number of cigarettes smoked at week 12 and a significant change in cravings
      at week 4 among smokers attempting to quit. Difference in smoking abstinence
      rates was not measured in this study.

PMID- 30302180
TI  - A forgetful and angry old lady.
AB  - Dementia is typically characterized by the deterioration of cognitive abilities
      and is a common disorder among the elderly in Malaysia. However, behavioral and
      psychological symptoms are also present in approximately 90% of dementia
      patients.1 We report the manifestation of these symptoms in an elderly woman with
      dementia and the treatment thereof.

PMID- 30302181
TI  - Chest discomfort in a patient with dengue - is it an acute myocardial infarction?
AB  - Cardiovascular symptoms presenting in a patient with dengue fever may post a
      diagnostic dilemma. We describe a case of dengue myocarditis mimicking an acute
      myocardial infarction in a 56-year-old woman.

PMID- 30302182
TI  - Kimura Disease: A differential diagnosis in a nephrotic child.
AB  - Kimura disease presents as benign lesion and is commonly present among the Asian
      population. It is a disease with a favourable prognosis and a peak age of onset
      in the third decade. It is a chronic inflammatory disorder of unknown etiology
      that involves the lymph nodes and subcutaneous tissues of the head and neck
      region. We report a case of a 15-year-old boy with multiple Kimura
      lymphadenopathies involving the left posterior auricular region as well as the
      anterior and posterior triangles of the neck.

PMID- 30302183
TI  - Metallic hair pin aspiration into the left tertiary bronchus.
AB  - Foreign body aspiration is commonly described in infants and children. However,
      recently, a new high-risk group was identified among young women, especially
      those from the Muslim population who wear the traditional hair scarf. This is due
      to the habit of holding the scarf pin in between the lips to free hands to adjust
      the scarf more easily. Talking, laughing, or coughing while fixing the scarf may
      result in inadvertent inhalation of the pin into the tracheobronchial tree. We
      present a case of scarf pin inhalation and the challenges encountered in managing
      this patient during the successful removal of the pin via flexible bronchoscopy
      under fluoroscopy guidance. This particular case was technically challenging for
      us as the sharp tip of the needle was pointing upward and piercing the bronchial
      mucosa.

PMID- 30302184
TI  - Non-specific skin purpura.
AB  - Essential thrombocythemia is one of the myeloproliferative neoplasms. Palpable
      purpura is a rare manifestation that may delay diagnosis and treatment. We report
      a case of essential thrombocythemia in a 50-year-old man, who presented with
      recurrent thigh pain for the past one year with nonspecific localized purpura.
      His full blood count revealed isolated thrombocytosis of 880,000/uL with an
      impression of myeloproliferative disorder from peripheral blood film. He was
      referred urgently to the hematology team, which proceeded with a venesection. His
      condition improved with hydroxyurea. This was a rare case of chronic presentation
      of myeloproliferative neoplasm detected at a primary care clinic.

PMID- 30302185
TI  - Purple urine bag syndrome: A startling phenomenon of purple urine in a urine
      drainage bag. A primary care approach and literature review.
AB  - Purple urine bag syndrome (PUBs) is a rare and startling phenomenon of purple
      discolouration in the urine or urinary catheter and bag. It is reported in
      chronically debilitated elderly patients, mostly in women on long-term urinary
      catheters. Its prevalence is strikingly more common in nursing home residents.
      Several factors contribute to the formation of indigo (blue) and indirubin (red)
      pigments from a breakdown of dietary tryptophan, which stains the urine purple.
      These factors include constipation, dysmotility of the bowel, bowel bacterial
      overgrowth, dehydration, and urinary tract infection. The presence of purple
      urine may cause undue alarm to both the patient and the doctor. Thus, we present
      this case report on an 86-year-old woman, a nursing home resident on a long-term
      urinary catheter, who presented to the primary care clinic. Her urine cleared
      after antibiotic therapy, replacement of her urinary catheter, and supportive
      management, which included hydration and nutrition. In addition to these
      measures, reducing the time between urinary catheter changes was recommended to
      prevent recurrence of this condition.

PMID- 30302186
TI  - No thumbs up for the boy!

PMID- 30302188
TI  - Crowding and the Furrow Illusion.
AB  - A spot moves vertically across a large grating of oblique parallel lines. When
      viewed peripherally, the motion path looks oblique, close to the orientation of
      the background grating. Even when the grating's orientation is concealed by
      crowding, it can still deflect the spot's perceived motion path.

PMID- 30302187
TI  - The effect of age on vertex-based measures of the grey-white matter tissue
      contrast in autism spectrum disorder.
AB  - Background: Histological evidence suggests that autism spectrum disorder (ASD) is
      accompanied by a reduced integrity of the grey-white matter boundary. This has
      also recently been confirmed by a structural neuroimaging study in vivo reporting
      significantly reduced grey-white matter tissue contrast (GWC) in adult
      individuals (18-42 years of age) with ASD relative to typically developing (TD)
      controls. However, it remains unknown whether the neuroanatomical differences in
      ASD at the grey-white matter boundary are stable across development or are age
      dependent. Methods: Here, we examined differences in the neurodevelopmental
      trajectories of GWC in a cross-sectional sample of 77 male ASD individuals and 76
      typically developing (TD) controls across childhood and early adulthood (from 7
      to 25 years). Results: Using nested model comparisons, we first established that
      the developmental trajectory of GWC is complex in many regions across the cortex
      and includes linear and non-linear effects of age. Second, while ASD individuals
      have significantly reduced GWC overall, these differences are age-dependent and
      are most prominent during childhood (< 15 years). Conclusions: Taken together,
      our findings suggest that differences in GWC in ASD are unlikely to reflect
      atypical grey matter cytoarchitecture alone, but may also represent other aspects
      of the cortical architecture such as age-dependent variability in myelin
      integrity.

PMID- 30302189
TI  - Characterization of the structure, cells, and cellular mechanobiological response
      of human plantar fascia.
AB  - In this study, we report that human plantar fascia consists of two distinct
      tissues with differential structural properties. These tissues also contain
      stem/progenitor cells with differential biological properties. The
      mechanobiological responses of these two plantar fascia stem cells also differ in
      terms of expression of collagen I and IV, non-ligament-related genes, and
      proinflammatory genes. The production of inflammatory agents (prostaglandin E2,
      interleukin-6) and matrix degradative enzymes (matrix metalloproteinase-1, matrix
      metalloproteinase-2) are also different between the two types of plantar fascia
      stem cells. Based on the findings from this study, we suggest that plantar
      fasciitis results from the aberrant mechanobiological responses of the stem cells
      from plantar fascia sheath and core tissues. Our findings may also be used to
      devise tissue engineering approaches to treat plantar fascia injury effectively.

PMID- 30302190
TI  - Retrieval of a retained video capsule endoscope with laparoscopic surgery.
AB  - Capsule endoscopy (CE) is commonly used for examining and diagnosing
      gastrointestinal disease, especially small bowel disease. Capsule retention is a
      well-known and significant complication of CE and requires surgical or endoscopic
      removal. Most reports described the retrieval of retained CE via laparotomy. We
      report a case of successful retrieval of the capsule using laparoscopic surgery.

PMID- 30302191
TI  - Spontaneous rupture of the urinary bladder due to bacterial cystitis.
AB  - We report a case of spontaneous rupture of the urinary bladder (SRUB) due to
      bacterial cystitis in a 76-year-old woman with chief complaint of abdominal pain
      a day before presentation. She had fever (38.0 degrees C), and her systolic blood
      pressure dropped to 70 mmHg; she was referred to our hospital, where she was
      admitted with a diagnosis of ileus. However, her abdominal pain worsened the
      following day, and abdominal CT showed free air. Emergency laparotomy was
      performed for suspicion of digestive tract perforation, which revealed a small
      hole at the dome of the urinary bladder and another at the peritoneum. Suture
      repair was performed. We reviewed the abdominal CT on admission and noted that
      the perforation of the urinary bladder was present during admission, whereas that
      of the peritoneum occurred the following day. SRUB is rare, and bacterial
      cystitis rarely causes it; thus, accurate diagnosis and proper treatment are
      essential.

PMID- 30302193
TI  - Development of shellfish allergy after exposure to dual immune checkpoint
      blockade.
AB  - Hepatocellular carcinoma (HCC) is a major health problem worldwide with limited
      systemic therapies available. Immunotherapy is a fast-moving field that is
      quickly evolving as a treatment for HCC with three recent clinical trials
      published treating HCC with immune checkpoint inhibitors with promising results.
      Checkpoint inhibition may lead to a unique adverse event profile with the
      potential to cause immune-related adverse events by unbalancing the immune
      system. Here, we report a case of a 61-year-old male with advanced HCC who
      developed a shellfish allergy after completing three cycles of combination of
      tremelimumab and durvalumab therapy.

PMID- 30302192
TI  - Systemic treatments for hepatocellular carcinoma: challenges and future
      perspectives.
AB  - Sorafenib has been the only approved systemic treatment of hepatocellular
      carcinoma (HCC) for almost a decade. Recently, two new drugs showed positive
      results in two Phase III studies. The RESORCE trial identified regorafenib as a
      valid second-line treatment for patients progressing to sorafenib, the REFLECT
      trial showed that lenvatinib is noninferior to sorafenib as front-line treatment.
      Following these trials, the therapeutic scenario will be dominated by anti-VEGFR
      drugs, with three different molecules showing a proven anticancer activity. Some
      open problems still remain and different immunotherapy trials are underway,
      following promising preliminary results. In this review we analyze: the most
      recent advancements about patients treated with sorafenib; the results of RESORCE
      and REFLECT trials; and the ongoing Phase III clinical trials. Finally, we
      discuss how they could address the current problems and possibly reshape the
      future of the systemic treatments for HCC.

PMID- 30302194
TI  - The impact of antiviral therapy on hepatocellular carcinoma epidemiology.
AB  - The development of nucleos(t)ide analogs and direct antiviral agents has
      revolutionized the management of chronic infection with HBV and HCV,
      respectively. These regimens allow to expand treatment to virtually all infected,
      including those with poor hepatic reserve and those with severe comorbidities. As
      a result, permanent suppression of HBV and eradication of HCV has been achieved
      in almost all treated patients, resulting in substantial clinical benefits. In
      several cohorts, these successes have translated into a reduction of the
      incidence of hepatocellular carcinoma that was more frequently observed in
      patients with less advanced hepatitis, whereas liver cancer was more often
      associated with male gender, cirrhosis, alcohol abuse and diabetes.

PMID- 30302195
TI  - Molecular classification of hepatocellular adenomas: impact on clinical practice.
AB  - Hepatocellular adenomas are rare benign liver tumors usually developing in young
      women using oral contraception. The two main complications are hemorrhage (10
      20%) and malignant transformation into hepatocellular carcinoma (<5%). A
      molecular classification has been recently updated in six major subgroups, linked
      to risk factors, histology, imaging and clinical features: adenomas inactivated
      for HNF1A, inflammatory adenomas, beta-catenin-activated adenomas mutated in exon
      3, beta-catenin-activated adenomas mutated in exon 7-8, sonic hedgehog adenomas,
      and unclassified adenomas. Indeed, beta-catenin-mutated adenomas in exon 3 are
      associated with malignant transformation, and sonic hedgehog adenomas with
      bleeding. This new nosology of hepatocellular adenomas will help to stratify
      patients according to risk of complications and will guide therapeutics in the
      future.

PMID- 30302196
TI  - How Rap and its GEFs control liver physiology and cancer development. C3G
      alterations in human hepatocarcinoma.
AB  - Rap proteins regulate liver physiopathology. For example, Rap2B promotes
      hepatocarcinoma (HCC) growth, while Rap1 might play a dual role. The RapGEF,
      Epac1, activates Rap upon cAMP binding, regulating metabolism, survival, and
      liver regeneration. A liver specific Epac2 isoform lacking cAMP-binding domain
      also activates Rap1, promoting fibrosis in alcoholic liver disease. C3G (RapGEF1)
      is also present in the liver, but mainly as shorter isoforms. Its function in the
      liver remains unknown. Information from different public genetic databases
      revealed that C3G mRNA levels increase in HCC, although they decrease in
      metastatic stages. In addition, several mutations in RapGEF1 gene are present,
      associated with a reduced patient survival. Based on this, C3G might represent a
      new HCC diagnostic and prognostic marker, and a therapeutic target.

PMID- 30302197
TI  - De novo hepatocellular carcinoma occurrence in hepatitis C cirrhotics treated
      with direct-acting antiviral agents.
AB  - Aim: Recent studies raise concerns for higher incidence of hepatocellular
      carcinoma (HCC) after direct-acting antiviral therapy for hepatitis C virus
      (HCV). Methods: In this study, using analysis of liver imaging pre- and post-DAA
      treatment, we queried new occurrence or 'de novo' of HCC in patients with HCV
      cirrhosis treated with DAAs. Of 150 patients who met study criteria, 7 (4.7%; 95%
      CI: 2.1-9.5%) patients developed de novo HCC which did not differ from historical
      rates of 3% (p = 0.22). Results: Notably, patients with decompensated cirrhosis
      had significantly higher rate of de novo HCC (9.3%; 95% CI: 3.12-22.2%; p =
      0.04). Conclusion: Our data support the need for continued surveillance for HCC
      in HCV cirrhotics even after successful therapy.

PMID- 30302198
TI  - Molecular heterogeneity in hepatocellular carcinoma.

PMID- 30302199
TI  - Propylene glycol-free melphalan as conditioning regimen for autologous
      transplantation in myeloma.
AB  - High-dose melphalan has been the drug of choice for preparative regimens for
      autologous stem cell transplantation in multiple myeloma. Propylene-free
      melphalan (EvomelaTM) is a newer formulation of melphalan, which incorporates
      Captisol(r) to produce a stable product upon reconstitution. In addition to
      avoiding propylene glycol with its' potential side effects, this approach
      improves the overall stability of reconstituted melphalan and can ensure intended
      dose delivery. In this paper, we review the published literature regarding this
      formulation. We focus on its' chemistry, pharmacokinetics and clinically
      available data for its use in myeloma autologous stem cell transplantation
      setting.

PMID- 30302201
TI  - Dielectrophoretic recovery of DNA from plasma for the identification of chronic
      lymphocytic leukemia point mutations.
AB  - Aim: Circulating cell free (ccf) DNA contains information about mutations
      affecting chronic lymphocytic leukemia (CLL). The complexity of isolating DNA
      from plasma inhibits the development of point-of-care diagnostics. Here, we
      introduce an electrokinetic method that enables rapid recovery of DNA from
      plasma. Materials & methods: ccf-DNA was isolated from 25 ul of CLL plasma using
      dielectrophoresis. The DNA was used for PCR amplification, sequencing and
      analysis. Results: The ccf-DNA collected from plasma of 5 CLL patients revealed
      identical mutations to those previously identified by extracting DNA from CLL
      cells from the same patients. Conclusion: Rapid dielectrophoresis isolation of
      ccf-DNA directly from plasma provides sufficient amounts of DNA to use for
      identification of point mutations in genes associated with CLL progression.

PMID- 30302200
TI  - Erythrocyte encapsulated l-asparaginase (GRASPA) in acute leukemia.
AB  - l-asparaginase, an enzyme originally derived from Escherichia coli, represents a
      major drug in the treatment of acute lymphoblastic leukemia. However, the
      occurrence of major adverse effects often leads to early withdrawal of the
      enzyme. Main side effects include immune-allergic reactions, coagulopathy,
      pancreatitis and hepatic disorders. Novel asparaginase formulations and
      alternative sources have been developed to address this issue, but the results
      were not totally satisfactory. l-asparaginase loaded red blood cells (RBCs;
      GRASPA) represent a new asparaginase presentation with reduced immunological
      adverse reactions. RBCs protect l-asparaginase, enhance its half-life and reduce
      the occurrence of adverse events. We reviewed the history, biology and clinical
      experiences with l-asparaginase, and the characteristics and first clinical
      experiences with GRASPA in the treatment of acute leukemia.

PMID- 30302203
TI  - Current treatment options in elderly patients with chronic lymphocytic leukemia.

PMID- 30302204
TI  - Cancer treatment in the extreme elderly: case study of a 100-year-old lymphoma
      patient.
AB  - Limited data are available on the treatment of older adults with cancer.
      Comorbidities may preclude the administration of effective therapies,
      particularly in the extreme elderly. Comprehensive geriatric assessment can
      identify specific weaknesses of the patient and predict unexpected toxicities,
      thus enabling an optimized treatment strategy in this population. We report a
      case of the successful management of a 99-year-old female lymphoma patient with a
      strong wish for active treatment to improve quality of life and prolong survival
      past her 100th birthday. This case demonstrates that cancer treatment in the
      extreme elderly is possible and highlights the need for a formalized treatment
      plan based on geriatric assessment, frank discussion with patients and families,
      and defined goals of therapy.

PMID- 30302205
TI  - Five-year direct costs of acute lymphoblastic leukemia pediatric patients
      undergoing allogeneic stem cell transplant.
AB  - Aim: To assess the 5-year healthcare resource utilization (HRU) and direct payer
      costs following allogeneic hematopoietic stem cell transplants (HSCTs) in acute
      lymphoblastic leukemia pediatric patients using data from two large US
      administrative databases. Patients & methods: Among the 209 patients with acute
      lymphoblastic leukemia, HRU and costs were described over the up to 5 years after
      the HSCT. Results: HRU and costs following the HSCTs were substantial. The
      highest average costs and most intensive HRU were observed within the first year
      following the HSCTs (49 outpatient visits; 29 laboratory service visits; 68
      inpatient days), with a first year cost of US$683,099 and substantial costs over
      the following years. Conclusion: HRU and direct costs associated with allogeneic
      HSCTs are substantial.

PMID- 30302202
TI  - Targeting B-cell receptor signaling in leukemia and lymphoma: how and why?
AB  - B-lymphocytes are dependent on B-cell receptor (BCR) signaling for the constant
      maintenance of their physiological function, and in many B-cell malignancies this
      signaling pathway is prone to aberrant activation. This understanding has led to
      an ever-increasing interest in the signaling networks activated following
      ligation of the BCR in both normal and malignant cells, and has been critical in
      establishing an array of small molecule inhibitors targeting BCR-induced
      signaling. By dissecting how different malignancies signal through BCR,
      researchers are contributing to the design of more customized therapeutics which
      have greater efficacy and lower toxicity than previous therapies. This allows
      clinicians access to an array of approaches to best treat patients whose
      malignancies have BCR signaling as a driver of pathogenesis.

PMID- 30302208
TI  - Management of multiple myeloma: the impact of ixazomib's approval in Canada.
AB  - Donna E Reece speaks to Laura Dormer, Commissioning Editor: Dr Donna E Reece is a
      Professor of Medicine and Director of the Program for Multiple Myeloma and
      Related Diseases in the Department of Medical Oncology and Hematology at Princess
      Margaret Hospital/University of Toronto. She earned a Bachelor of Arts degree at
      the University of Texas, Austin, and graduated as valedictorian with a medical
      degree from Baylor College of Medicine, Houston, Texas. She completed an
      internship in Internal Medicine at the University of Colorado Affiliated
      Hospitals, a residency and Chief Residency in Internal Medicine at Jewish
      Hospital, St Louis, and a Fellowship in Hematology/Oncology at Barnes Hospital,
      Washington University, St Louis, Missouri. She was a fellow and later a
      leukemia/stem cell transplant staff physician at Vancouver General
      Hospital/University of British Columbia for over 10 years. She then served as
      Director of the Outpatient Leukemia/Stem Cell Transplant Program, and later
      interim director, of the Blood and Marrow Transplant Program of the Markey Cancer
      Center at the University of Kentucky, Lexington, Kentucky until her appointment
      to Princess Margaret Hospital in Toronto in 2001. Dr Reece received the David and
      Molly Bloom Chair in Myeloma Research in 2009. She is currently the co-chair of
      the Multiple Myeloma Clinical Trials Group of the National Cancer Institute of
      Canada, member of the Scientific Advisory Board of the International Myeloma
      Foundation, and member of the Project Review Committee of the MMRC (Multiple
      Myeloma Research Consortium). She is also the Chief Medical Officer of the
      Myeloma Canada Research Network and serves on the board of directors of Myeloma
      Canada. Her career focus has been in the areas of hematopoietic stem cell
      transplantation, lymphoid malignancies and plasma cell dyscrasias. She has
      published numerous articles in these areas.

PMID- 30302207
TI  - Identifying targetable genetic features in primary CNS lymphoma.

PMID- 30302206
TI  - Diagnostic and treatment of adult Philadelphia chromosome-positive acute
      lymphoblastic leukemia.
AB  - The outcome of adult patients with Philadelphia chromosome-positive (Ph+) acute
      lymphoblastic leukemia (ALL) has improved substantially with the introduction of
      tyrosine kinase inhibitors (TKIs). TKIs are now integral components of therapy
      for Ph+ ALL. The current consensus is that they improve patient outcomes compared
      with historical control patients treated with chemotherapy alone, and increase
      the number of patients able to receive stem cell transplant. New challenges have
      emerged with respect to induction of resistance mainly via Abelson tyrosine
      kinase mutations. Several novel kinase inhibitors with significantly more potent
      antileukemic activity are currently being developed. Furthermore novel immune
      therapies, which recruit or modify patient's own T cells to fight leukemic cells,
      are being developed and could find an important place in Ph+ ALL therapy by few
      years. In this article, we reviewed treatment approaches in adults with Ph+ ALL
      with a focus on TKIs and combined chemotherapy regimens.

PMID- 30302209
TI  - Trisenox: a paradigm shift in APL therapy, an interview with Francesco Lo-Coco.
AB  - Francesco Lo-Coco speaks to Sebastian Dennis-Beron, Commissioning Editor:
      Francesco Lo-Coco is currently a full professor of hematology and head of the
      Laboratory of Integrated Diagnosis of Oncohematologic Diseases at the Department
      of Biomedicine and Prevention of the University Tor Vergata of Roma. He obtained
      his MD degree from the University of Pisa in 1981, and his specialization in
      clinical and laboratory hematology is from the University La Sapienza of Rome in
      1985. From 1992 to 1994, he has trained on molecular genetics of lymphomas at
      Columbia University, New York. His main scientific interest and research
      activities include genetic characterization, monitoring and treatment of
      hematologic tumors, particularly acute myeloid leukemia and acute promyelocytic
      leukemia (APL). He has published over 390 internationally peer-reviewed articles,
      mainly focused on molecular diagnosis and follow-up of leukemia as well as on
      treatment of APL. He chairs at present the APL subcommittee of the Italian
      National Cooperative Group, GIMEMA. He served as president of the Italian Society
      of Experimental Hematology, chairman of the Education Committee of the European
      Hematology Association, board member of the Italian Foundation for Cancer
      Research, member of the Committe on Health Research of the Italian Ministry of
      Health and member of the Editorial Board of the journals Leukemia, Journal of
      Clinical Oncology and Haematologica.

PMID- 30302211
TI  - A look back at 2016 in International Journal of Hematologic Oncology.

PMID- 30302212
TI  - Are FLT3 inhibitors likely to improve FLT3-mutated acute myeloid leukemia in the
      foreseeable future?

PMID- 30302210
TI  - Current first- and second-line treatment options in acute promyelocytic leukemia.
AB  - Outcome of acute promyelocytic leukemia (APL) has remarkably improved during the
      last 30 years, especially after the identification of PML-RARA oncogene as a key
      in the pathogenesis of APL and all-trans retinoic acid as therapeutic agent.
      Arsenic trioxide has been recently demonstrated to be the most effective single
      antileukemic agent and it has also showed synergistic action when combined with
      all-trans retinoic acid, decreasing relapse rate especially in low/intermediate
      risk settings. Therapeutic advances led to complete remission rates of more than
      90%, modifying disease history. In relapse setting, arsenic trioxide-based
      regimens showed efficacy for the achievement of second molecular complete
      remission. The most challenging issue in APL management remains the significant
      early deaths rate, nowadays the principal reason for treatment failure.

PMID- 30302213
TI  - New insights into effective targeted therapy for the treatment of adult acute
      lymphoblastic leukemia.

PMID- 30302216
TI  - Updated classification and novel treatment prospective for nodal peripheral T
      cell lymphomas.

PMID- 30302214
TI  - Potential role for all-trans retinoic acid in nonpromyelocytic acute myeloid
      leukemia.
AB  - All-trans retinoic acid (ATRA) has been very successful in the subtype of acute
      myelogenous leukemia known as acute promyelocytic leukemia due to targeted
      reactivation of retinoic acid signaling. There has been great interest in
      applying this form of differentiation therapy to other cancers, and numerous
      clinical trials have been initiated. However, ATRA as monotherapy has thus far
      shown little benefit in nonacute promyelocytic leukemia acute myelogenous
      leukemia. Here, we review the literature on the use of ATRA in combination with
      chemotherapy, epigenetic modifying agents and targeted therapy, highlighting
      specific patient populations where the addition of ATRA to existing therapies may
      provide benefit. Furthermore, we discuss the impact of recent whole genome
      sequencing efforts in leading the design of rational combinatorial approaches.

PMID- 30302217
TI  - The bone marrow transplant clinical nurse specialist in hemato-oncology: an
      interview with Anthony Nolan Nurse Specialist Susan Paskar.
AB  - Susan Paskar speaks to Sebastian Dennis-Beron, Commissioning Editor: Susan
      qualified in 1997 as a registered nurse and has 20 years of experience, in a
      range of specialties including hematology, medical and surgical oncology, general
      surgery, bariatric, breast, endocrine, head & neck, liver, urology and bone
      marrow/stem cell transplant. Working in both the UK and the USA, in regional
      transplant centers since 2002, she is considered expert in care of the bone
      marrow transplant patient from point of referral to long term follow-up care and
      palliation. She has been responsible for development and implementation of a
      Nurse-led late-effects post-bone marrow transplant service at the Freeman
      Hospital in Newcastle upon Tyne, as their Anthony Nolan Nurse Specialist.

PMID- 30302215
TI  - Targeted therapies in the treatment of adult acute myeloid leukemias: current
      status and future perspectives.
AB  - The rapid advancement of next-generation sequencing techniques and the
      identification of molecular driver events responsible for leukemia development
      are opening the door to new pharmacologic-targeted agents to tailor treatment of
      acute myeloid leukemia (AML) in individual patients. However, the use of targeted
      therapies in AML has met with only modest success. Molecular studies have
      identified AML subsets characterized by driver mutational events, such as NPM1,
      FLT3-ITD and IDH1-2 mutations, and have provided preclinical evidence that the
      targeting of these mutant molecules could represent a valuable therapeutic
      strategy. Recent studies have provided the first pieces of evidence that FLT3
      targeting in FLT3-mutant AMLs, IDH1/2 inhibition in IDH-mutant AMLs and targeting
      membrane molecules preferentially expressed on leukemic progenitor/stem cells,
      such as CD33 and CD123, represent a clinically valuable strategy.

PMID- 30302219
TI  - Chronic lymphocytic leukemia: "The times they are a-changin".

PMID- 30302218
TI  - Current challenges in the management of follicular lymphoma.
AB  - Although typically indolent in nature, follicular lymphoma remains an ongoing
      challenge for practicing oncologists. While response rates >90% can be achieved
      with rituximab-based chemoimmunotherapy in advanced stage patients, the complete
      remission rates are substantially lower and patients inevitably relapse. The
      inability to achieve a complete remission and an early progression of disease
      have recently been determined to be indicative of poorer long-term outcomes. A
      greater understanding of the pathogenesis of follicular lymphoma has enabled the
      development of targeted therapies, which may improve standard treatment
      approaches. Examples include lenalidomide and obinutuzumab, which are currently
      in front-line Phase III investigation. Other therapies of interest include small
      molecule inhibitors, immune checkpoint inhibitors and chimeric antigen receptor T
      cells.

PMID- 30302220
TI  - Targeting sphingosine kinase 1 in acute myeloid leukemia: translation to clinic.

PMID- 30302221
TI  - The influence of antiretroviral therapy on clinical aspects of HIV-related
      lymphoma.

PMID- 30302222
TI  - Living 20 years with multiple myeloma: an interview with Phil Falkowitz.
AB  - Phil Falkowitz speaks to Sebastian Dennis-Beron, Commissioning Editor: Phil
      Falkowitz is 67 a year oldman who has lived with Multiple myeloma patient for 20
      years. He has been married to his wife Barbara for 44 years and is currently
      raising a family of three. Phil graduated from Temple University (PA, USA) in
      1972. He is one of the founders and charter members of the Philadelphia Multiple
      MyelomaNetworking Group which is now a fund raising entity of the I.M.F. Phil's
      interest inclassic cars has extended to his e-mail address thus resulting in
      G67vette@comcast.net (G for green).

PMID- 30302224
TI  - Opportunities for targeting gene regulatory factors in B-cell acute lymphoblastic
      leukemia.

PMID- 30302223
TI  - Understanding the molecular basis of acute myeloid leukemias: where are we now?
AB  - Although the treatment modalities for acute myeloid leukemia (AML) have not
      changed much over the past 40 years, distinct progress has been made in
      deciphering the basic biology underlying the pathogenesis of this group of
      hematological disorders. Studies show that AML development is a multicause,
      multistep and multipathway process. Accordingly, AMLs constitute a heterogeneous
      group of diseases. The thorough understanding of the molecular basis of AML is
      paving the way for better therapeutic approaches. Multiple novel drugs are being
      introduced and new, more efficient and less toxic formulations of conventional
      therapeutics are becoming available. Here, we review the recent advances in the
      comprehension of the molecular processes that lead to the onset of AML and its
      translation into clinical practice.

PMID- 30302225
TI  - Early mortality and survival in older adults with acute myeloid leukemia.

PMID- 30302226
TI  - How can we better predict treatment outcomes in classical Hodgkin's lymphoma?

PMID- 30302227
TI  - Primary diffuse large B-cell lymphoma of the CNS: a rare case of spontaneous
      remission.
AB  - There is no consensus on the optimal therapy for primary CNS lymphoma.
      Conventional treatment modalities include chemotherapy and radiation therapy,
      which carry significant risks of morbidity and mortality. In systemic lymphomas,
      there are situations where non-Hodgkin lymphomas have resolved spontaneously. We
      now report the case of a nonimmunocompromised patient with primary CNS lymphoma
      who underwent a spontaneous remission with a durable response. This case suggests
      that not all patients with primary CNS lymphomas require aggressive treatment
      with chemotherapy and radiation therapy.

PMID- 30302229
TI  - Interview with Dr Philip McCarthy.
AB  - Philip McCarthy speaks to Roshaine Wijayatunga, Senior Editor: Oncology Philip
      McCarthy completed his MD at Tufts University School of Medicine, Boston, MA, USA
      and his Internal Medicine Residency at Yale, New Haven Hospital, New Haven, CT,
      USA. His Fellowship was completed at Brigham and Women's Hospital and the Dana
      Farber Cancer Insitute, Harvard University, Boston, MA, USA. His research
      interests are devoted to developing novel intensive and reduced intensity
      allogeneic (allo) and autologous (auto) hematopoietic stem cell transplant (HSCT)
      approaches for the treatment of hematologic disorders, leading to improved
      patient outcomes and decreased toxicity. He has over 20 years of experience
      treating HSCT patients and directing clinical and translational HSCT research
      studies. He has served as chair or co-chair of several clinical trials including
      CALGB 100104, a Phase III clinical trial evaluating lenalidomide maintenance
      after auto-HSCT for multiple myeloma (MM). This study demonstrated an improved
      progression-free and overall survival for MM patients receiving lenalidomide
      maintenance therapy after auto-HSCT. The Roswell Park Comprehensive Cancer Center
      Blood and Marrow Transplant team has developed a systematic approach to the
      evaluation and treatment of HSCT patients with a specific focus on predicting and
      minimizing treatment-related mortality. The team participates with a core group
      of basic science and clinical researchers who are committed to the investigation
      of the complications of auto- and allo-HSCT and to the developing novel
      approaches to improve outcomes.

PMID- 30302230
TI  - A discussion of blood cancers and the MPN landmark survey.
AB  - Professor Claire Harrison speaks to Roshaine Wijayatunga, managing commissioning
      editor: Professor Claire Harrison became a consultant at Guy's and St Thomas'
      hospital in 2001. She is also deputy clinical director of cancer and hematology.
      She has influenced major advances in her field, including the description of key
      mutations and designing/leading global clinical trials, for example, the first
      JAK inhibitor trial in Europe. She is the chief investigator for several other
      international and national clinical trials. She has strong international
      collaborations and authors many papers in peer-reviewed journals such as the New
      England Journal of Medicine and Blood. She has worked with enthusiastic patients
      to create a patient charity, MPN Voice. She is an internationally regarded expert
      in her field as a patient advocate.

PMID- 30302228
TI  - Defibrotide for the treatment of hepatic veno-occlusive disease/sinusoidal
      obstruction syndrome with multiorgan failure.
AB  - Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome
      (VOD/SOS), is a potentially life-threatening and unpredictable complication of
      hematopoietic stem cell transplantation (HSCT). Characterized by a prothrombotic
      hypofibrinolytic state, VOD/SOS typically presents with hyperbilirubinemia,
      ascites, weight gain and painful hepatomegaly; VOD/SOS with multiorgan failure
      may be associated with >80% mortality. Treatment has been mainly supportive.
      However, defibrotide is now approved in the USA for treatment of hepatic VOD/SOS
      with renal or pulmonary dysfunction following HSCT and in the European Union for
      treatment of severe hepatic VOD/SOS post-HSCT. In vitro evidence suggests
      defibrotide may restore thrombotic-fibrinolytic balance at the endothelial level
      and protect endothelial cells. Defibrotide has demonstrated significant reduction
      in VOD/SOS-related mortality and resolved VOD/SOS-related symptoms, with a
      manageable safety profile.

PMID- 30302231
TI  - Untreated chronic lymphocytic leukemia in Lebanese patients: an observational
      study using standard karyotyping and FISH.
AB  - Aim: We aimed to understand the biology of chronic lymphocytic leukemia (CLL)
      patients in Lebanon. Materials & methods: We applied conventional cytogenetic and
      FISH studies on Lebanese patients diagnosed with CLL and undergoing a watch and
      wait approach. Results: Our study disclosed 53.6% of patients with aberrant
      karyotypes among which 26.7% were complex karyotypes. Genetic aberrations
      included del(13q14) 46.4%, 14q32 translocation in 25%, trisomy 12 in 14.3%,
      del(17p13) and del(11q22) in 7.1% each. The deletion of 6q21/6q23 was not found
      in any of our patients. Conclusion: The higher prevalence of del(13q14) as a sole
      abnormality could be the primary event in inducing CLL. The del(17p13) and
      del(11q22) followed as potential drivers for progression in CLL patients with a
      watch and wait approach.

PMID- 30302232
TI  - Long-term outcomes of rituximab, temozolomide and high-dose methotrexate without
      consolidation therapy for lymphoma involving the CNS.
AB  - Aim: To describe the long-term outcomes of patients with lymphoma in the CNS
      treated with rituximab, temozolomide and high-dose methotrexate without
      consolidation therapy. Patients & methods: A retrospective cohort study of 46
      consecutive patients with primary CNS lymphoma (PCNSL, 27 patients) or secondary
      CNS involvement of diffuse large B-cell lymphoma (DLBCL, 19 patients) who were
      treated with rituximab on day 1 in combination with high-dose methotrexate (days
      1 and 15) and temozolomide (days 1-5) in 28-day cycles without further
      consolidation. Results: Median follow-up was 21.2 months. Patients received a
      median of five cycles (range 1-15). Median overall survival (OS) was 26 months
      and median progression-free survival was 8.6 months. At 3 years, 37% of patients
      were alive and without evidence of disease. The patients with PCNSL had a
      significantly higher response rates (ORR 81 vs 47%; p = 0.015) and longer median
      OS (55.3 vs 4.8 months; p < 0.01) than those with secondary CNS DLBCL. Toxicities
      were mild and manageable. Conclusion: The rituximab, temozolomide and
      methotrexate regimen is an effective therapy for patients with PCNSL without the
      toxicities typically associated with consolidation therapy.

PMID- 30302233
TI  - Radioimmunotherapy-based conditioning regimen prior to autologous stem cell
      transplantation in non-Hodgkin lymphoma.
AB  - Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy and the
      sixth cause of death from cancer in the USA. Autologous stem cell transplantation
      (ASCT) is a potentially curative therapeutic option for many NHL patients.
      Choosing the most effective conditioning regimen prior to ASCT can lead to longer
      survival in these patients, and, as in many cases of high risk NHL, the only
      potentially curative option is stem cell transplantation. Radioimmunotherapy
      (RIT) is based on using radiolabeled monoclonal antibodies against tumoral
      antigens. Since lymphoma cells are sensitive to radiation, RIT has become a
      potential approach in treating NHL. In this review, we have discussed the
      efficacy and safety of RIT as an alternative conditioning regimen prior to ASCT.

PMID- 30302234
TI  - Management of older adults with acute lymphoblastic leukemia: challenges &
      current approaches.
AB  - The management of acute lymphoblastic leukemia (ALL) in older patients is
      challenging. Older patients often have multiple comorbidities and poor
      performance status, and disease factors associated with poor prognosis are more
      common in this age group. Patient and disease-related factors should be taken
      into account to determine whether intensive therapy is appropriate. The use of
      comorbidity indices and comprehensive geriatric assessment tools can be valuable
      in this setting. Fit patients should be considered for aggressive therapies
      including allogeneic hematopoietic stem cell transplantation, whereas low
      intensity options may be more suitable for the frail. The Philadelphia (Ph)
      chromosome is present in up to half of the cases of ALL in older patients. The
      incorporation of TK inhibitors into the treatment plans of older patients with Ph
      positive ALL has improved the outcomes significantly. For less fit patients with
      Ph-positive ALL, the use of TK inhibitors with reduced-intensity chemotherapy or
      steroids alone results in high rates of remission, but, without further
      consolidation, relapses are inevitable. Many novel targeted and immunotherapeutic
      agents are being developed, offering more effective and tolerable treatment
      options.

PMID- 30302235
TI  - Isolated hypoglossal nerve palsy as a presenting symptom of metastatic peripheral
      T-cell lymphoma - not otherwise specified (PTCL-NOS): a unique case & a review of
      the literature.
AB  - Extensive and significant technological advancements have enhanced the
      sensitivity and accuracy of the pathologic classification, diagnosis, and
      therapeutics of lymphoma. These advances have prompted a more comprehensive
      understanding of neoplastic behavior and have led to improvements in both
      treatment and prognosis. This paper presents a comprehensive review of lymphoma
      and features a case report of a unique presentation of peripheral T-cell lymphoma
      - not otherwise specified that presented with isolated hypoglossal nerve
      dysfunction.

PMID- 30302236
TI  - Chart review across EU5 in MM post-ASCT patients.
AB  - Aim: To understand the current treatment patterns, clinical outcomes and
      healthcare resource utilization-associated costs for multiple myeloma patients,
      post autologous stem cell transplant (ASCT) across Europe. Patients & methods:
      Medical records were used to abstract data for 337 multiple myeloma patients who
      had received ASCT. Results: Following ASCT, 7% received maintenance therapy prior
      to progression. Lenalidomide was the most frequently prescribed maintenance,
      second- and third-line therapy. Monthly resource use was considerably lower in
      patients who received maintenance therapy (?638.14 vs ?1001.74). Median time to
      progression was longer for patients who had received maintenance therapy.
      Conclusion: The study highlights the diversity in current treatment patterns post
      ASCT. Results suggest patients who receive maintenance therapy have a prolonged
      remission period, and as a result their associated healthcare resource
      utilization is spread across the treatment pathway.

PMID- 30302237
TI  - The transformative journey of chronic myeloid leukemia.

PMID- 30302238
TI  - Spinal epidural lipomatosis presenting to a U.S. Veterans Affairs pain and
      rehabilitation department: a report of two cases.
AB  - Background: Spinal epidural lipomatosis is an uncommon source of neurogenic
      claudication. We present two cases of spinal epidural lipomatosis as it relates
      to diagnosis, management, and a possible association with common medical
      intervention. Case presentation: Case 1: 63-year old male patient presented with
      neurogenic claudication symptoms, but without evidence of bony central canal
      stenosis on lumbar computed tomography. He entered a trial of spinal manipulation
      with transient beneficial gains after seven appointments, but no durable change
      in neurogenic claudication. An MRI was recommended at this point which revealed
      grade III spinal epidural lipomatosis at the L5/S1 level.Case 2: 51-year old male
      patient presented to a pain management physician with radicular symptoms for a
      series of lumbar epidural steroid injections. He completed a series of three
      lumbar epidural steroid injections with only short-term benefit. A repeat MRI
      demonstrated the presence of grade I (borderline grade II) spinal epidural
      lipomatosis. Conclusions: The first case illustrates a limitation of ruling out
      central canal stenosis with computed tomography for patients unable to undergo an
      MRI. The second case demonstrates a possible association between steroid
      injections and spinal epidural lipomatosis. An association of this kind has not
      been established; further research is needed to determine the significance.

PMID- 30302239
TI  - Plasmonic bacteria on a nanoporous mirror via hydrodynamic trapping for rapid
      identification of waterborne pathogens.
AB  - A rapid, precise method for identifying waterborne pathogens is critically needed
      for effective disinfection and better treatment. However, conventional methods,
      such as culture-based counting, generally suffer from slow detection times and
      low sensitivities. Here, we developed a rapid detection method for tracing
      waterborne pathogens by an innovative optofluidic platform, a plasmonic bacteria
      on a nanoporous mirror, that allows effective hydrodynamic cell trapping,
      enrichment of pathogens, and optical signal amplifications. We designed and
      simulated the integrated optofluidic platform to maximize the enrichment of the
      bacteria and to align bacteria on the nanopores and plasmonic mirror via
      hydrodynamic cell trapping. Gold nanoparticles are self-assembled to form antenna
      arrays on the surface of bacteria, such as Escherichia coli and Pseudomonas
      aeruginosa, by replacing citrate with hydroxylamine hydrochloride in order to
      amplify the signal of the plasmonic optical array. Owing to the synergistic
      contributions of focused light via the nanopore geometry, self-assembled
      nanoplasmonic optical antennas on the surface of bacteria, and plasmonic mirror,
      we obtain a sensitivity of detecting E. coli as low as 102 cells/ml via surface
      enhanced Raman spectroscopy. We believe that our label-free strategy via an
      integrated optofluidic platform will pave the way for the rapid, precise
      identification of various pathogens.

PMID- 30302240
TI  - Multimode optical fiber transmission with a deep learning network.
AB  - Multimode fibers (MMFs) are an example of a highly scattering medium, which
      scramble the coherent light propagating within them to produce seemingly random
      patterns. Thus, for applications such as imaging and image projection through an
      MMF, careful measurements of the relationship between the inputs and outputs of
      the fiber are required. We show, as a proof of concept, that a deep neural
      network can learn the input-output relationship in a 0.75 m long MMF.
      Specifically, we demonstrate that a deep convolutional neural network (CNN) can
      learn the nonlinear relationships between the amplitude of the speckle pattern
      (phase information lost) obtained at the output of the fiber and the phase or the
      amplitude at the input of the fiber. Effectively, the network performs a
      nonlinear inversion task. We obtained image fidelities (correlations) as high as
      ~98% for reconstruction and ~94% for image projection in the MMF compared with
      the image recovered using the full knowledge of the system transmission
      characterized with the complex measured matrix. We further show that the network
      can be trained for transfer learning, i.e., it can transmit images through the
      MMF, which belongs to another class not used for training/testing.

PMID- 30302241
TI  - Attenuation artifacts in light sheet fluorescence microscopy corrected by
      OPTiSPIM.
AB  - Light sheet fluorescence microscopy (LSFM) is rapidly becoming an essential
      technology for mesoscopic imaging of samples such as embryos and adult mouse
      organs. However, LSFM can suffer from optical artifacts for which there is no
      intrinsic solution. The attenuation of light due to absorbing material causes
      "shadow" artifacts along both the illumination and detection paths. Several
      approaches have been introduced to reduce this problem, including scanning
      illumination and multi-view imaging. However, neither of these approaches
      completely eliminates the problem. If the distribution of the absorbing material
      is complex, shadows cannot be avoided. We introduce a new approach that relies on
      multi-modal integration of two very different mesoscopic techniques. Unlike LSFM,
      optical projection tomography (OPT) can operate in transmission mode to create a
      voxel map of the 3D distribution of the sample's optical attenuation. Here, we
      demonstrate a hybrid instrument (OPTiSPIM) that can quantify this attenuation and
      use the information to correct the shadow artifacts of LSFM.

PMID- 30302242
TI  - GOBO projection for 3D measurements at highest frame rates: a performance
      analysis.
AB  - Aperiodic sinusoidal patterns that are cast by a GOBO (GOes Before Optics)
      projector are a powerful tool for optically measuring the surface topography of
      moving or deforming objects with very high speed and accuracy. We optimised the
      first experimental setup that we were able to measure inflating car airbags at
      frame rates of more than 50 kHz while achieving a 3D point standard deviation of
      ~500 um. Here, we theoretically investigate the method of GOBO projection of
      aperiodic sinusoidal fringes. In a simulation-based performance analysis, we
      examine the parameters that influence the accuracy of the measurement result and
      identify an optimal pattern design that yields the highest measurement accuracy.
      We compare the results with those that were obtained via GOBO projection of phase
      shifted sinusoidal fringes. Finally, we experimentally verify the theoretical
      findings. We show that the proposed technique has several advantages over
      conventional fringe projection techniques, as the easy-to-build and cost
      effective GOBO projector can provide a high radiant flux, allows high frame
      rates, and can be used over a wide spectral range.

PMID- 30302243
TI  - Recurrent diabetic myonecrosis -an under-diagnosed cause of acute painful swollen
      limb in long standing diabetics.
AB  - Diabetic myonecrosis (DMN) is an under-diagnosed complication of long-standing
      poorly controlled diabetes mellitus. It presents as abrupt pain and swelling of
      the extremity, mostly lower limbs. Diagnosis is often delayed as it mimics a
      number of clinical entities such as deep vein thrombosis (DVT), cellulitis,
      necrotizing fasciitis and malignancy. Failure to properly identify this condition
      can result in increased morbidity through exposure to unnecessary tests and
      biopsy. A 56-year-old male with a history of complicated type 2 diabetes
      mellitus, hypertension presented to emergency with gradually worsening left calf
      pain for last 2 weeks. A lower-extremity venous Doppler was negative for DVT.
      Magnetic resonance imaging (MRI) was suggestive of muscle edema likely of
      inflammatory etiology. Muscle biopsy revealed myonecrosis with ischemic myopathy
      and was negative for vasculitis or inflammatory myopathy. He was managed
      conservatively and his symptoms resolved in 4 weeks. After 6 months he had
      recurrence in right thigh which was managed conservatively too. Given these
      findings, a diagnosis of recurrent diabetic myonecrosis was made. Myonecrosis is
      a less known microvascular complications of diabetes and should always be keep in
      mind when evaluating a diabetic patient with muscle pain. Diagnosis can be made
      on MRI in appropriate clinical settings. The clinical course is usually self
      limiting and patients respond well to supportive medical therapy that involves
      bed rest, strict glycemic control along with analgesic.

PMID- 30302244
TI  - Laparoscopic cholecystectomy using the PINPOINT(r) Endoscopic Fluorescence
      Imaging System with intraoperative fluorescent imaging for acute cholecystitis: A
      case report.
AB  - We report on a laparoscopic cholecystectomy (LC) for acute cholecystitis (AC)
      using the bright field/full-color fluorescence laparoscope system PINPOINT(r)
      (Novadaq, Mississauga, ON, Canada). The patient was an 85-year-old man who was
      diagnosed with moderate AC. Indocyanine green (ICG) was administered just before
      surgery, and we used only PINPOINT(r) to perform the LC. The advantage of this
      procedure is that it can be performed while viewing ICG fluorescence in the
      cystic duct. Since the gallbladder is imaged with this technique, it is also
      advantageous from the perspective of deciding at which layer to detach the
      gallbladder from the liver. The operative time was 81 minutes, and blood loss was
      5 ml. There were no perioperative complications, and the patient was discharged
      on post-operative day 6.

PMID- 30302245
TI  - Factors during training which predict future use of minimally invasive thoracic
      surgery.
AB  - Background: While minimally invasive thoracic surgery (MIS) has increased
      nationwide over the years, most patients undergoing lung and esophageal
      resections still undergo an open approach. We performed a national survey to
      analyze factors associated with a propensity to perform MIS after completing a
      cardiothoracic training program. Materials and methods: Cardiothoracic surgery
      trainees in 2 or 3-year programs from 2010 to 2016 were sent an online survey
      regarding the numbers and types of cases performed during training and current
      practice patterns as attending surgeons. Comfort level with MIS was also
      assessed. Responses were recorded and analyzed using SPSS. Results: One hundred
      thirty-six trainees responded, with a mean of 121 lobectomies (30-250) and 40
      esophagectomies (8-110) performed during training. Mean minimally invasive
      lobectomy and esophagectomy rates during training were 53% and 30% respectively.
      A greater ratio of MIS procedures performed during training correlated with a
      higher rate performed as an attending (lobectomies, p = 0.04; esophagectomies, p
      = 0.01) and a greater comfort level with performing these procedures
      (lobectomies, p = 0.01 and esophagectomies, p < 0.01). Conclusions: Based on
      these results, performing a greater ratio of minimally invasive lobectomies and
      esophagectomies during fellowship training increases the likelihood of performing
      them as an attending.

PMID- 30302246
TI  - Prevalence of Helicobacter pylori in asymptomatic patients at surgical outpatient
      department: Harare hospitals.
AB  - Background: Helicobacter pylori infection is present in more than 50% of the
      world's population. The estimated life time risk of peptic ulcer disease is 20
      percent and of gastric cancer is 1-2 percent. Materials and methods: A cross
      sectional study was done at two Central hospitals in Harare, Zimbabwe, with the
      objective being to estimate the prevalence of Helicobacter pylori infection in
      asymptomatic individuals. Other objectives were to determine the association of
      the Helicobacter pylori infection with potential risk factors.Four hundred and
      fifty patients visiting the outpatient surgical clinics for other complaints
      other than upper gastrointestinal symptoms were recruited in the study. Drops of
      whole blood were obtained by fingertip puncture from each patient. The Onsite H.
      pylori Combo Rapid Test was used to confirm the presence or absence of antibodies
      against Helicobacter pylori. A questionnaire was used to record the
      sociodemographics of the participants. Results: Three hundred patients, 186 males
      (62%) and 114 females (38%) participated. The prevalence of Helicobacter pylori
      infection was 67.7 percent (203/300). The prevalence of H pylori infection was
      significantly correlated with increasing age (p = 0.012), sharing of a bed with
      siblings during childhood (p = 0.013) and the mode of sanitation methods (p =
      0.023). There was no association found between H pylori infection and other risk
      factors such as; gender, level of education, employment status or number of rooms
      in a house. Conclusion: H. pylori infection prevalence was significantly
      associated with increasing age, sharing of a bed with siblings during childhood
      and the mode of sanitation used. Clinicians and the public have to be aware of
      the important role of H pylori in upper gastrointestinal disease. Use of better
      sanitation methods, appropriate hygiene, avoidance of over-crowding amongst other
      measures should be encouraged as a means to reduce the acquisition and
      transmission of H pylori.

PMID- 30302248
TI  - Assessing the feasibility of parent participation in a commercial weight loss
      program to improve child body mass index and weight-related health behaviors.
AB  - Objectives: Little is known about how children's health might be affected by
      parents' participation in commercial weight loss programs. Given that more than
      3.2 million people subscribe to just one commercial weight loss program, Weight
      Watchers, any secondary effects on children's weight-related health behaviors
      (e.g. dietary behaviors, physical activity, and sedentary time) and body mass
      index from parent participation in commercial weight loss programs may have
      significant public health implications. This study examined the feasibility of
      conducting a study to assess such effects. Methods for recruitment and retention,
      and perceived acceptability and satisfaction among participants in small-scale
      preliminary study, were evaluated. Changes in body mass index and health
      behaviors among the parent-child dyads were also measured to test whether a
      larger-scale study would be warranted. Methods: This was an 8-week, pre-post
      observational feasibility study involving 20 parent-child dyads where both
      members had overweight or obesity. Physical and behavioral data were collected at
      baseline and 8 weeks from both members of the dyads. Parenting data were
      collected at the same time periods through parents' self-report. Bivariate
      correlation was used to quantify the associations in changes for dyad members.
      Results: Feasibility goals for retention and perceived acceptability/satisfaction
      among participants were met. We reached approximately 80% of our enrollment goal.
      Parents showed a significant decrease in body mass index of 0.53 points (p <
      0.05), while children showed a significant increase in raw body mass index (0.42,
      p < 0.05) and body mass index percentile (0.59, p < 0.05). However, correlation
      between changes in parent body mass index and changes in children body mass index
      percentile was positively correlated (r = 0.24, p = 0.31). A decrease in parent
      intake of total fat was associated with a decrease in the intake of fat in their
      children (r = 0.47, p < 0.05). Conclusion: Our findings support the viability of
      a larger-scale follow-up to assess the potential of using parent-only commercial
      weight loss program as a mechanism for improving health behaviors and body mass
      index in children with overweight or obesity.

PMID- 30302249
TI  - Quality assessment of controlled clinical trials published in Orthopaedics and
      Traumatology journals in Spanish: An observational study through handsearching
      and evidence mapping.
AB  - Few Orthopaedics and Traumatology journals from Latin America and Spain are
      indexed in major databases; controlled clinical trials published in these
      journals cannot be exhaustively retrieved using electronic literature searches.
      We aimed to identify, describe and assess the quality of controlled clinical
      trials published in Orthopaedics and Traumatology journals from Latin America and
      Spain through handsearching and evidence mapping methods. We identified
      controlled clinical trials published in eligible Orthopaedics/Traumatology
      journals in Spanish until July 2017 by handsearching. Data were extracted for
      controlled clinical trials main characteristics and the Cochrane risk of bias
      tool was used to assess the controlled clinical trials methodological quality. In
      addition, we mapped the main findings of these trials. As a result, we assessed
      5631 references in 29 eligible journals of which 57 were controlled clinical
      trials (1.0%). Controlled clinical trials were published between 1995 and 2017 at
      a rate of 2.5 per year. Journals from Spain and Mexico published around 63% of
      the controlled clinical trials identified. The median sample size of patients
      enrolled was 60 (range = 30-300 participants). About conditions assessed, 38.5%
      of controlled clinical trials assessed issues related to knee conditions, 15.7%
      about hip and 10.5% about trauma or spine. The risk of bias domains most affected
      was selective reporting bias and random sequence generation. In addition, only
      two and seven trials had low risk of bias in all items related to
      participant/personnel and outcome assessment blindings, respectively. More than
      40% of studies did not report differences on benefits/harms between the
      interventions assessed. As a conclusion, the number of controlled clinical trials
      published in Orthopaedics/Traumatology journals from Latin America and Spain is
      low. These controlled clinical trials had important methodological shortcomings
      and were judged as unclear or high risk of bias. These trials are now available
      in CENTRAL for their potential inclusion in systematic reviews and other
      documents of synthesis.

PMID- 30302250
TI  - Photodistributed sarcoidosis: a case report and approach to management.
AB  - Sarcoidosis is an idiopathic disease, characterized by non-caseating granulomas
      in multiple organs/tissues. Cutaneous involvement occurs in approximately one
      quarter of patients with a wide variety of presenting morphologies. This case
      report describes a case of photodistributed sarcoidosis, a rare cutaneous
      variant, with systemic involvement. A 42-year-old man presented with a history of
      a pruritic, rash with photoexacerbated annular plaques along with arthralgias and
      bone pain. Compared to previous reports of photodistributed sarcoidosis, our case
      presented with annular plaques rather than papules, and there was no prior
      exposure to ionizing radiation. He was treated successfully with prednisone and
      hydroxychloroquine. It is important to include sarcoidosis in the differential of
      photodistributed dermatoses.

PMID- 30302247
TI  - Management of severe acute exacerbations of COPD: an updated narrative review.
AB  - Background: Patients with chronic obstructive pulmonary disease (COPD) may
      experience an acute worsening of respiratory symptoms that results in additional
      therapy; this event is defined as a COPD exacerbation (AECOPD). Hospitalization
      for AECOPD is accompanied by a rapid decline in health status with a high risk of
      mortality or other negative outcomes such as need for endotracheal intubation or
      intensive care unit (ICU) admission. Treatments for AECOPD aim to minimize the
      negative impact of the current exacerbation and to prevent subsequent events,
      such as relapse or readmission to hospital. Main body: In this narrative review,
      we update the scientific evidence about the in-hospital pharmacological and non
      pharmacological treatments used in the management of a severe AECOPD. We review
      inhaled bronchodilators, steroids, and antibiotics for the pharmacological
      approach, and oxygen, high flow nasal cannulae (HFNC) oxygen therapy, non
      invasive mechanical ventilation (NIMV) and pulmonary rehabilitation (PR) as non
      pharmacological treatments. We also review some studies of non-conventional drugs
      that have been proposed for severe AECOPD. Conclusion: Several treatments exist
      for severe AECOPD patients requiring hospitalization. Some treatments such as
      steroids and NIMV (in patients admitted with a hypercapnic acute respiratory
      failure and respiratory acidosis) are supported by strong evidence of their
      efficacy. HFNC oxygen therapy needs further prospective studies. Although
      antibiotics are preferred in ICU patients, there is a lack of evidence regarding
      the preferred drugs and optimal duration of treatment for non-ICU patients. Early
      rehabilitation, if associated with standard treatment of patients, is recommended
      due to its feasibility and safety. There are currently few promising new drugs or
      new applications of existing drugs.

PMID- 30302251
TI  - Variable response of post-Mohs surgery telangiectasias to KTP laser: A case
      report.
AB  - A common but under-recognized complication of Mohs micrographic surgery is the
      development of surgical site telangiectasias after repair. Treatment with pulsed
      dye laser has shown good results in treating periscar telangiectasias, while
      treatment with KTP laser has never been studied for this complication. We report
      the findings in six patients with persistent telangiectasias post-Mohs
      micrographic surgery and their response to treatment with KTP laser. After one
      treatment with KTP laser, the severity of telangiectasias, scar erythema, and
      patient and physician-rated improvement were recorded. Response to KTP laser was
      variable. However, this case series suggests that KTP laser may have the
      potential to improve the appearance of periscar telangiectasia after Mohs
      micrographic surgery.

PMID- 30302252
TI  - Pulmonary hernia: Case report and review of the literature.
AB  - Pulmonary hernia (PH) is an uncommon condition. We report a case of PH secondary
      to thoracic surgical intervention. In addition to the rarity, the peculiarity of
      the case is given by the clinical course as it is characterized by a clinical
      latency before the onset. The patient showed risk factors such as obesity and
      poliomyelitis infection sequelae. We also reviewed the literature about this
      topic.

PMID- 30302253
TI  - Recurrent respiratory papillomatosis: the role of cidofovir.
AB  - Recurrent respiratory papillomatosis (RRP) is a rare condition that affects the
      respiratory system. It is caused by human papilloma virus (HPV) infection.
      Usually infection and papilloma growth is limited to 6-12 months duration;
      however, some patients have persistent disease, resulting in long-term symptoms
      and the need for recurrent intervention. Predominant symptoms include shortness
      of breath, reduced exercise tolerance and voice deterioration during flares.
      Current gold-standard management is through resection via microdebrider, CO2
      laser, cryotherapy, electrocoagulation, Nd: YAG laser or pulse-dye laser.
      However, despite these therapies, approximately 20% of patients require adjuvant
      therapy. We discuss the use of intralesional cidofovir in the management of
      tracheal papillomatosis. Cidofovir's mechanism of action involves incorporating
      into the virus DNA chain and therefore, inhibiting the viral DNA polymerization
      process and hence replication.

PMID- 30302254
TI  - Monitoring of sedation depth in intensive care unit by therapeutic drug
      monitoring? A prospective observation study of medical intensive care patients.
AB  - Background: Analgosedation is a cornerstone therapy for mechanically ventilated
      patients in intensive care units (ICU). To avoid inadequate sedation and its
      complications, monitoring of analgosedation is of great importance. The aim of
      this study was to investigate whether monitoring of analgosedative drug
      concentrations (midazolam and sufentanil) might be beneficial to optimize
      analgosedation and whether drug serum concentrations correlate with the results
      of subjective (Richmond Agitation-Sedation Scale [RASS]/Ramsay Sedation Scale)
      and objective (bispectral (BIS) index) monitoring procedures. Methods: Forty-nine
      intubated, ventilated, and analgosedated critically ill patients treated in ICU
      were clinically evaluated concerning the depth of sedation using RASS Score,
      Ramsay Score, and BIS index twice a day. Serum concentrations of midazolam and
      sufentanil were determined in blood samples drawn at the same time. Clinical and
      laboratory data were statistically analyzed for correlations using the Spearman's
      rank correlation coefficient rho (rho). Results: Average age of the population
      was 57.8 +/- 16.0 years, 61% of the patients were males. Most frequent causes for
      ICU treatments were sepsis (22%), pneumonia (22%), or a combination of both
      (25%). Serum concentrations of midazolam correlated weakly with RASS (rho = -
      0.467) and Ramsay Scores (rho = 0.476). Serum concentrations of sufentanil
      correlated weakly with RASS (rho = - 0.312) and Ramsay Scores (rho = 0.295).
      Correlations between BIS index and serum concentrations of midazolam (rho = -
      0.252) and sufentanil (rho = - 0.166) were low. Conclusion: Correlations between
      drug serum concentrations and clinical or neurophysiological monitoring
      procedures were weak. This might be due to intersubject variability, polypharmacy
      with drug-drug interactions, and complex metabolism, which can be altered in
      critically ill patients. Therapeutic drug monitoring is not beneficial to
      determine depth of sedation in ICU patients.

PMID- 30302255
TI  - Comparative proteomic analysis provides insight into a complex regulatory network
      of taproot formation in radish (Raphanus sativus L.).
AB  - The fleshy taproot of radish is an important storage organ determining its yield
      and quality. Taproot thickening is a complex developmental process in radish.
      However, the molecular mechanisms governing this process remain unclear at the
      proteome level. In this study, a comparative proteomic analysis was performed to
      analyze the proteome changes at three developmental stages of taproot thickening
      using iTRAQ approach. In total, 1862 differentially expressed proteins (DEPs)
      were identified from 6342 high-confidence proteins, among which 256 up-regulated
      proteins displayed overlapped accumulation in S1 (pre-cortex splitting stage) vs.
      S2 (cortex splitting stage) and S1 vs. S3 (expanding stage) pairs, whereas 122 up
      regulated proteins displayed overlapped accumulation in S1 vs. S3 and S2 vs. S3
      pairs. Gene Ontology (GO) and pathway enrichment analysis showed that these DEPs
      were mainly involved in several processes such as "starch and sucrose
      metabolism", "plant hormone signal transduction", and "biosynthesis of secondary
      metabolites". A high concordance existed between iTRAQ and RT-qPCR at the mRNA
      expression levels. Furthermore, association analysis showed that 187, 181, and 96
      DEPs were matched with their corresponding differentially expressed genes (DEGs)
      in S1 vs. S2, S1 vs. S3, and S2 vs. S3 comparison, respectively. Notably, several
      functional proteins including cell division cycle 5-like protein (CDC5), expansin
      B1 (EXPB1), and xyloglucan endotransglucosylase/hydrolase protein 24 (XTH24) were
      responsible for cell division and expansion during radish taproot thickening
      process. These results could facilitate a better understanding of the molecular
      mechanism underlying taproot thickening, and provide valuable information for the
      identification of critical genes/proteins responsible for taproot thickening in
      root vegetable crops.

PMID- 30302256
TI  - The MADS transcription factor CmANR1 positively modulates root system development
      by directly regulating CmPIN2 in chrysanthemum.
AB  - Plant root systems are essential for many physiological processes, including
      water and nutrient absorption. MADS-box transcription factor (TF) genes have been
      characterized as the important regulators of root development in plants; however,
      the underlying mechanism is largely unknown, including chrysanthemum. Here, it
      was found that the overexpression of CmANR1, a chrysanthemum MADS-box TF gene,
      promoted both adventitious root (AR) and lateral root (LR) development in
      chrysanthemum. Whole transcriptome sequencing analysis revealed a series of
      differentially expressed unigenes (DEGs) in the roots of CmANR1-transgenic
      chrysanthemum plants compared to wild-type plants. Functional annotation of these
      DEGs by alignment with Gene Ontology (GO) terms and biochemical pathway Kyoto
      Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that
      CmANR1 TF exhibited "DNA binding" and "catalytic" activity, as well as
      participated in "phytohormone signal transduction". Both chromatin
      immunoprecipitation-polymerase chain reaction (ChIP-PCR) and gel electrophoresis
      mobility shift assays (EMSA) indicated the direct binding of CmPIN2 to the
      recognition site CArG-box motif by CmANR1. Finally, a firefly luciferase imaging
      assay demonstrated the transcriptional activation of CmPIN2 by CmANR1 in vivo.
      Overall, our results provide novel insights into the mechanisms of MADS-box TF
      CmANR1 modulation of both AR and LR development, which occurs by directly
      regulating auxin transport gene CmPIN2 in chrysanthemum.

PMID- 30302257
TI  - Proteomic analysis of heat stress resistance of cucumber leaves when grafted onto
      Momordica rootstock.
AB  - Various biotic and abiotic stresses threaten the cultivation of future
      agricultural crops. Among these stresses, heat stress is a major abiotic stress
      that substantially reduces agricultural productivity. Many strategies to enhance
      heat stress tolerance of crops have been developed, among which is grafting.
      Here, we show that Momordica-grafted cucumber scions have intrinsically enhanced
      chlorophyll content, leaf area, and net photosynthetic rate under heat stress
      compared to plants grafted onto cucumber rootstock. To investigate the mechanisms
      by which Momordica rootstock enhanced cucumber scions heat stress tolerance,
      comparative proteomic analysis of cucumber leaves in response to rootstock
      grafting and/or heat stress was conducted. Seventy-seven differentially
      accumulated proteins involved in diverse biological processes were identified by
      two-dimensional electrophoresis (2-DE) in conjunction with matrix-assisted laser
      desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI
      TOF/TOF MS). The following four main categories of proteins were involved:
      photosynthesis (42.8%), energy and metabolism (18.2%), defense response (14.3%),
      and protein and nucleic acid biosynthesis (11.7%). Proteomic analysis revealed
      that scions grafted onto Momordica rootstocks upregulated more proteins involved
      in photosynthesis compared to scions grafted onto cucumber rootstocks under heat
      stress and indicated enhanced photosynthetic capacity when seedlings were exposed
      to heat stress. Furthermore, the expression of photosynthesis-related genes in
      plants grafted onto Momordica rootstocks significantly increased in response to
      heat stress. In addition, increased high-temperature tolerance of plants grafted
      onto Momordica rootstock was associated with the accumulation of ribulose-1,5
      bisphosphate carboxylase/oxygenase (Rubisco) and oxygen-evolving enhancer protein
      1 (OEE1). Taken together, the data indicated that Momordica rootstock might
      alleviate growth inhibition caused by heat stress by improving photosynthesis,
      providing valuable insight into enhancing heat stress tolerance in the global
      warming epoch.

PMID- 30302258
TI  - Transcriptomic analyses identify albino-associated genes of a novel albino tea
      germplasm 'Huabai 1'.
AB  - Albinism in shoots of tea plants is a common phenotypic expression which gives
      the tea infusion a pleasant umami taste. A novel natural albino mutant tea
      germplasm containing high amino acids content was found and named as 'Huabai 1'.
      'Huabai 1' has white jade tender shoots under low temperature and turns green
      with increased temperature. In order to understand the molecular mechanism of
      color change in leaf of 'Huabai 1', transcriptome analysis was performed to
      identify albino-associated differentially expressed genes (DEGs). A total of 483
      DEGs were identified from white shoots of 'Huabai 1' compared to its green
      shoots. There were 15 DEGs identified to be involved in phenylpropanoid
      biosynthesis, which account for the majority of characterized DEGs. The
      metabolites related to phenylpropanoid biosynthesis revealed similar expression
      pattern of DEGs. Furthermore, metabolic pathways such as ubiquonone, tyrosine,
      and flavonoid biosynthesis associated with phenylpropanoid biosynthesis could
      also contribute to the color change in 'Huabai 1' tender shoots. Protein-protein
      interaction analysis revealed a hub protein NEDD8 (CSA009575) which interacted
      with many regulated genes in spliceosome, nitrogen metabolism, phenylpropanoid
      biosynthesis, and other pathways. In conclusion, the findings in this study
      indicate that the color change of 'Huabai 1' tender shoots is a combined effect
      of phenylpropanoid biosynthesis pathway and other metabolic pathways including
      flavonoid biosynthesis in tea plants. Chlorophyll biosynthesis-related genes
      LHCII and SGR may also play some roles in color change of 'Huabai 1'.

PMID- 30302259
TI  - Multiple haploids, triploids, and tetraploids found in modern-day "living fossil"
      Ginkgo biloba.
AB  - Ginkgo biloba, the last extant representative of a lineage of Mesozoic
      gymnosperms, is one of the few seed plants with an exceptionally long (~300 Myr)
      evolutionary history free of genome-wide duplications (polyploidy). Despite this
      genome conservatism, we have recently found a viable spontaneous tetraploid
      Ginkgo sapling during routine screening of several plants, demonstrating that
      natural polyploidy is possible in Ginkgo. Here we provide a much wider flow
      cytometry survey of ploidy in some European Ginkgo collections, and own seedlings
      (>2200 individuals and ~200 cultivars). We found a surprisingly high level of
      ploidy variation in modern-day Ginkgo and documented altogether 13 haploid, 3
      triploid, and 10 tetraploid Ginkgo plants or cultivars, most of them being
      morphologically distinct from common diploids. Haploids frequently produced
      polyploid (dihaploid) buds or branches. Tetraploids showed some genome size
      variation. The surveyed plants provide a unique resource for future Ginkgo
      research and breeding, and they might be used to accelerate the modern
      diversification of this nearly extinct plant lineage.

PMID- 30302262
TI  - Acute kidney injury in a Tanzanian boy following multiple bee stings in resource
      limited setting: a case report.
AB  - Bee sting has been identified as among causative agents of nephrotoxic acute
      tubular necrosis which may lead to acute kidney injury. Bee envenomation has
      medicinal properties but when a higher dose is inoculated may cause severe
      anaphylaxis with very poor prognosis. We report a 12-year-old boy with acute
      kidney injury following multiple bee stings who recovered well after
      hemodialysis.

PMID- 30302260
TI  - The USDA cucumber (Cucumis sativus L.) collection: genetic diversity, population
      structure, genome-wide association studies, and core collection development.
AB  - Germplasm collections are a crucial resource to conserve natural genetic
      diversity and provide a source of novel traits essential for sustained crop
      improvement. Optimal collection, preservation and utilization of these materials
      depends upon knowledge of the genetic variation present within the collection.
      Here we use the high-throughput genotyping-by-sequencing (GBS) technology to
      characterize the United States National Plant Germplasm System (NPGS) collection
      of cucumber (Cucumis sativus L.). The GBS data, derived from 1234 cucumber
      accessions, provided more than 23 K high-quality single-nucleotide polymorphisms
      (SNPs) that are well distributed at high density in the genome (~1 SNP/10.6 kb).
      The SNP markers were used to characterize genetic diversity, population
      structure, phylogenetic relationships, linkage disequilibrium, and population
      differentiation of the NPGS cucumber collection. These results, providing
      detailed genetic analysis of the U.S. cucumber collection, complement NPGS
      descriptive information regarding geographic origin and phenotypic
      characterization. We also identified genome regions significantly associated with
      13 horticulturally important traits through genome-wide association studies
      (GWAS). Finally, we developed a molecularly informed, publicly accessible core
      collection of 395 accessions that represents at least 96% of the genetic
      variation present in the NPGS. Collectively, the information obtained from the
      GBS data enabled deep insight into the diversity present and genetic
      relationships among accessions within the collection, and will provide a valuable
      resource for genetic analyses, gene discovery, crop improvement, and germplasm
      preservation.

PMID- 30302261
TI  - Differentially expressed protein and gene analysis revealed the effects of
      temperature on changes in ascorbic acid metabolism in harvested tea leaves.
AB  - Tea is an important non-alcoholic beverage worldwide. Tea quality is determined
      by numerous secondary metabolites in harvested tea leaves, including tea
      polyphenols, theanine, caffeine, and ascorbic acid (AsA). AsA metabolism in
      harvested tea leaves is affected by storage and transportation temperature.
      However, the molecular mechanisms underlying AsA metabolism in harvested tea
      leaves exposed to different storage and transportation temperature conditions
      remain unclear. Here we performed RP-HPLC to detect dynamic changes in AsA
      content in tea leaves subjected to high- (38  degrees C), low- (4  degrees C), or
      room-temperature (25  degrees C) treatments. The AsA distribution and levels in
      the treated tea leaves were analyzed using cytological-anatomical
      characterization methods. The differentially expressed CsAPX1 and CsDHAR2
      proteins, which are involved in the AsA recycling pathway, were identified from
      the corresponding proteomic data using iTRAQ. We also analyzed the expression
      profiles of 18 genes involved in AsA metabolism, including CsAPX1 and CsDHAR2.
      AsA was mainly distributed in tea leaf mesophyll cells. High- and low-temperature
      treatments upregulated the CsAPX1 and CsDHAR2 proteins and induced CsAPX and
      CsDHAR2 gene expression. These results indicated that the CsAPX1 and CsDHAR2
      proteins might have critical roles in AsA recycling in tea leaves. Our results
      provide a foundation for the in-depth investigation of AsA metabolism in tea
      leaves during storage and transportation, and they will promote better tea flavor
      in tea production.

PMID- 30302263
TI  - A 32-year-old man with hypoxemia and bilateral upper-lobe predominant ground
      glass infiltrates on chest imaging.
AB  - Diffuse alveolar hemorrhage (DAH) is a rare, but potentially fatal, complication
      of antiphospholipid syndrome, and may present with acute and fulminant symptoms.
      We report a case of DAH presenting as sudden onset dyspnea in a gentleman with
      known antiphospholipid syndrome. Chest computed tomography angiography with
      pulmonary embolism protocol showed right lower lobe segmental filling defects,
      upper-lobe predominant diffuse ground-glass opacities, and centrilobular nodules
      bilaterally. The presence of DAH can be confirmed by bronchoalveolar lavage with
      serial aliquots, but this procedure typically does not elucidate the specific
      etiology for the hemorrhage. The treatment for patients with severe disease
      typically consists of a combination of immunosuppressive medications in the form
      of high-dose intravenous glucocorticoids plus rituximab, cyclophosphamide or
      mycophenolate; and/or plasma exchange. This case both provides an example of high
      quality diagnostic imaging of diffuse alveolar hemorrhage as well as demonstrates
      the clinical and image-based improvement after treatment.

PMID- 30302264
TI  - Omphalocele and epigastric heteropagus: implications and treatment.
AB  - In heteropagus twins, the parasitic twin is incompletely formed which is attached
      to the autosite. We report a case of epigastric heteropagus twins with
      omphalocele. The parasite had two lower limbs, a rudimentary upper limb,
      genitalia with developed phallus and scrotum but absent testis. An omphalocele
      was present just below the attachment of the parasitic twin. A single kidney with
      ureter and a bladder filled with urine seen during exploration. The parasite
      bowel was attached to a sleeve of liver tissue from the autosite within the
      omphalocele sac and this connection was also the main source of its blood supply.
      Less than 20 cases of omphalocele with EH have been reported previously. The thin
      sac with underlying adherent bowel led us to go ahead with surgery in the
      neonatal period for both, excision of epigastric heteropagus and omphalocele
      repair. The rectus sheath around the omphalocele sac helped in the final wound
      closure.

PMID- 30302265
TI  - Bullous pemphigoid associated with ipilimumab therapy for advanced metastatic
      melanoma.
AB  - Immunotherapy is now being routinely used in the management of many cancers. It
      is therefore vital that all clinicians are aware of the diverse array of
      cutaneous manifestations that can result from their use, which can vary from mild
      to life threatening.

PMID- 30302266
TI  - Exome and copy number variation analyses of Mayer-Rokitansky-Kuster- Hauser
      syndrome.
AB  - Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by congenital
      absence of the vagina and uterus. We conducted genome-wide SNP analyses and exome
      sequencing to detect the causes of MRKH syndrome. We identified de novo variants
      of MYCBP2, NAV3, and PTPN3 in three families and a variant of MYCBP2 in a
      sporadic case. Here, we demonstrated the partial genetic makeup of Japanese MRKH
      syndrome.

PMID- 30302267
TI  - Predicting 3-Year Survival in Patients Receiving Maintenance Dialysis: An
      External Validation of iChoose Kidney in Ontario, Canada.
AB  - Background: Many patients with end-stage kidney disease (ESKD) do not appreciate
      how their survival may differ if treated with a kidney transplant compared with
      dialysis. A risk calculator (iChoose Kidney) developed and validated in the
      United States provides individualized mortality estimates for different treatment
      options (dialysis vs living or deceased donor kidney transplantation). The
      calculator can be used with patients and families to help patients make more
      educated treatment decisions. Objective: To validate the iChoose Kidney risk
      calculator in Ontario, Canada. Design: External validation study. Setting: We
      used several linked administrative health care databases from Ontario, Canada.
      Patients: We included 22 520 maintenance dialysis patients and 4505 kidney
      transplant recipients. Patients entered the cohort between 2004 and 2014.
      Measurements: Three-year all-cause mortality. Methods: We assessed model
      discrimination using the C-statistic. We assessed model calibration by comparing
      the observed versus predicted mortality risk and by using smoothed calibration
      plots. We used multivariable logistic regression modeling to recalibrate model
      intercepts using a correction factor, when appropriate. Results: In our final
      version of the iChoose Kidney model, we included the following variables: age (18
      80 years), sex (male, female), race (white, black, other), time on dialysis (<6
      months, 6-12 months, >12 months), and patient comorbidities (hypertension,
      diabetes, and/or cardiovascular disease). Over the 3-year follow-up period, 33.3%
      of dialysis patients and 6.2% of kidney transplant recipients died. The
      discriminatory ability was moderate (C-statistic for dialysis: 0.70, 95%
      confidence interval [CI]: 0.69-0.70, and C-statistic for transplant: 0.72, 95%
      CI: 0.69-0.75). The 3-year observed and predicted mortality estimates were
      comparable and even more so after we recalibrated the intercepts in 2 of our
      models (dialysis and deceased donor kidney transplantation). As done in the
      United States, we developed a Canadian Web site and an iOS application called
      Dialysis vs. Kidney Transplant- Estimated Survival in Ontario. Limitations:
      Missing data in our databases precluded the inclusion of all variables that were
      in the original iChoose Kidney (ie, patient ethnicity and low albumin). We were
      unable to perform all preplanned analyses due to the limited sample size.
      Conclusions: The original iChoose Kidney risk calculator was able to adequately
      predict mortality in this Canadian (Ontario) cohort of ESKD patients. After minor
      modifications, the predictive accuracy improved. The Dialysis vs. Kidney
      Transplant- Estimated Survival in Ontario risk calculator may be a valuable
      resource to help ESKD patients make an informed decision on pursuing kidney
      transplantation.

PMID- 30302268
TI  - Acute Kidney Injury Due to Inferior Vena Cava Stenosis After Liver
      Transplantation: A Case Report About the Importance of Hepatic Vein Doppler
      Ultrasound and Clinical Assessment.
AB  - Rationale: Acute kidney injury (AKI) is a frequent complication after liver
      transplantation. In some patients, prompt intervention targeted at a specific
      etiology is of paramount importance. Presenting concerns of the patients: A 25
      years old man with advanced liver cirrhosis caused by sclerosing cholangitis and
      autoimmune hepatitis underwent orthotopic liver transplantation. One month after
      surgery, severe AKI developed in conjunction with recurrent ascites and lower
      extremity edema. Notable clinical findings included a persistently low urinary
      sodium excretion, a bland urinary sediment, and an abnormally monophasic hepatic
      vein waveform on Doppler ultrasound. Diagnoses: Inferior vena cava stenosis.
      Interventions: Angioplasty with stent installation. Outcomes: Rapid improvement
      of renal function after stent installation. Lessons learned: The following case
      illustrates the importance of integrating clinical cues, ultrasound features, and
      laboratory findings. The combination of AKI associated with lower extremity
      edema, abnormal monophasic hepatic vein flow on Doppler ultrasound, and a low
      urinary sodium excretion after liver transplantation should evoke the possibility
      of inferior vena cava stenosis as the etiologic factor.

PMID- 30302269
TI  - Correction to: Changes in free amino acid content and hardness of beef while dry
      aging with Mucor flavus.
AB  - [This corrects the article DOI: 10.1186/s40781-018-0176-6.].

PMID- 30302272
TI  - Culturally congruent mentorship can reduce disruptive behavior among elementary
      school students: results from a pilot study.
AB  - Background: Our study objective was to examine the feasibility of implementing a
      culturally congruent mentorship pilot program, Youth-First (YF), that targets
      behavior modification among elementary school-aged children with disruptive
      behavior and a history of school suspension. We hypothesize that it is feasible
      to implement the YF program to reduce disruptive behaviors and recidivism of
      level III/IV infractions in school settings among at-risk African American
      students. Methods: We assessed program feasibility based on the success of
      program acceptance by parents/guardians, study enrollment, and intervention
      compliance by students. A pre/posttest study design was used to examine whether
      the YF program reduced recidivism of disruptive behavior among enrolled at-risk
      African American elementary school children between September 2016 and January
      2017. Generalized linear mixed models examined whether student behavioral scores
      improved over time and varied by program mentor. A McNemar test examined the
      reduction in cumulative incidence of level III/IV infractions pre-post YF program
      intervention. Results: Intervention acceptance, enrollment, and compliance were
      100% (95% confidence interval [CI] 86 to 100%), 100% (95% CI 86 to 100%), and 67%
      (95% CI 45 to 84%), respectively (N = 24). Overall, student behavioral scores
      improved and plateaued over time (Time2 effect: b = - 0.01, 95% CI - 0.02, <
      0.01); a two-week period was associated with a seven-point improvement (effect
      size: Cohen's d = 0.47, 95% CI 0.03, 0.94) in behavioral scores. Behavioral score
      improvements were class-specific, based on respectfulness behavior (b = 0.11, 95%
      CI < 0.01, 0.26). No recidivism of level III/IV infractions was reported during
      and post YF intervention. Conclusion: The integration of culturally congruent
      mentorship in elementary school-settings is feasible and can reduce risk of
      disruptive behaviors among at-risk African American students. Future studies
      should use randomized clinical trials to determine the effectiveness of
      culturally congruent mentorship interventions (void of potential selection and
      confounding biases) in reducing disruptive behavior, level III/IV infractions,
      and school suspensions among at-risk children.

PMID- 30302270
TI  - The use of computer-interpretable clinical guidelines to manage care complexities
      of patients with multimorbid conditions: A review.
AB  - Clinical practice guidelines (CPGs) document evidence-based information and
      recommendations on treatment and management of conditions. CPGs usually focus on
      management of a single condition; however, in many cases a patient will be at the
      centre of multiple health conditions (multimorbidity). Multiple CPGs need to be
      followed in parallel, each managing a separate condition, which often results in
      instructions that may interact with each other, such as conflicts in medication.
      Furthermore, the impetus to deliver customised care based on patient-specific
      information, results in the need to be able to offer guidelines in an integrated
      manner, identifying and managing their interactions. In recent years, CPGs have
      been formatted as computer-interpretable guidelines (CIGs). This enables
      developing CIG-driven clinical decision support systems (CDSSs), which allow the
      development of IT applications that contribute to the systematic and reliable
      management of multiple guidelines. This study focuses on understanding the use of
      CIG-based CDSSs, in order to manage care complexities of patients with
      multimorbidity. The literature between 2011 and 2017 is reviewed, which covers:
      (a) the challenges and barriers in the care of multimorbid patients, (b) the role
      of CIGs in CDSS augmented delivery of care, and (c) the approaches to alleviating
      care complexities of multimorbid patients. Generating integrated care plans,
      detecting and resolving adverse interactions between treatments and medications,
      dealing with temporal constraints in care steps, supporting patient-caregiver
      shared decision making and maintaining the continuity of care are some of the
      approaches that are enabled using a CIG-based CDSS.

PMID- 30302271
TI  - Rhamnolipids from Pseudomonas aeruginosa disperse the biofilms of sulfate
      reducing bacteria.
AB  - Biofilm formation is an important problem for many industries. Desulfovibrio
      vulgaris is the representative sulfate-reducing bacterium (SRB) which causes
      metal corrosion in oil wells and drilling equipment, and the corrosion is related
      to its biofilm formation. Biofilms are extremely difficult to remove since the
      cells are cemented in a polymer matrix. In an effort to eliminate SRB biofilms,
      we examined the ability of supernatants from Pseudomonas aeruginosa PA14 to
      disperse SRB biofilms. We found that the P. aeruginosa supernatants dispersed
      more than 98% of the biofilm. To determine the biochemical basis of this SRB
      biofilm dispersal, we examined a series of P. aeruginosa mutants and found that
      mutants rhlA, rhlB, rhlI, and rhlR, defective in rhamnolipids production, had
      significantly reduced levels of SRB biofilm dispersal. Corroborating these
      results, purified rhamnolipids dispersed SRB biofilms, and rhamnolipids were
      detected in the P. aeruginosa supernatants. Hence, P. aeruginosa supernatants
      disperse SRB biofilms via rhamnolipids. To determine the genetic basis of how the
      P. aeruginosa supernatants disperse SRB biofilms, a whole transcriptomic analysis
      was conducted (RNA-seq); based on this analysis, we identified four proteins
      (DVUA0018, DVUA0034, DVUA0066, and DVUA0084) of the D. vulgaris megaplasmid that
      influence biofilm formation, with production of DVUA0066 (a putative
      phospholipase) reducing biofilm formation 5.6-fold. In addition, the supernatants
      of P. aeruginosa dispersed the SRB biofilms more readily than protease in M9
      glucose minimum medium and were also effective against biofilms of Escherichia
      coli and Staphylococcus aureus.

PMID- 30302274
TI  - FDA guidance for next generation sequencing-based testing: balancing regulation
      and innovation in precision medicine.

PMID- 30302273
TI  - Abnormal gametogenesis induced by p53 deficiency promotes tumor progression and
      drug resistance.
AB  - The century-old embryonal/gametogenesis hypothesis of tumors could link diverse
      tumors' malignant features together likely representing the real "stemness" of
      tumors. However, the genetic evidence to validate abnormal gametogenesis in
      tumors remains lacking. Here we show that p53 deficiency elicits abnormal
      gametogenesis from primordial germ cell-like stage to late oocyte-like stage and
      subsequent parthenogenetic activation. The similar upregulation of abnormal
      gametogenesis by p53 deficiency is observed both in p53-/- mouse model and
      cultured cancer cells. Notably, germ cell-like cells isolated from distinct
      tumors from p53-/- mice and cancer cell lines display potent tumorigenicity
      potential. Abnormal oogenesis induced by p53 deficiency and then spontaneous
      parthenogenetic activation endow tumors with imitated embryonic development, life
      cycle, and therapeutic resistance. Our study establishes the genetic evidence to
      support embryonal/gametogenesis theory of tumors and reveals a pivotal role of
      p53 in restricting abnormal gametogenesis that may represent a novel aspect for
      p53's tumor suppression.

PMID- 30302277
TI  - Basal and starvation-induced autophagy mediates parasite survival during
      intraerythrocytic stages of Plasmodium falciparum.
AB  - The precise role of autophagy in P. falciparum remains largely unknown. Although
      a limited number of autophagy genes have been identified in this apicomplexan,
      only PfAtg8 has been characterized to a certain extent. On the basis of the
      expression levels of PfAtg8 and the putative PfAtg5, we report that the basal
      autophagy in this parasite is quite robust and mediates not only the
      intraerythrocytic development but also fresh invasion of red blood cells (RBCs)
      in the subsequent cycles. We demonstrate that the basal autophagy responds to
      both inducers and inhibitors of autophagy. In addition, the parasite survival
      upon starvation is temporally governed by the autophagy status. Brief periods of
      starvation, which induces autophagy, help survival while prolonged starvation
      decreases autophagy leading to stalled parasite growth and reduced invasion.
      Thus, starvation-induced autophagy is context dependent. Importantly, we report
      characterization of another autophagy marker in this parasite, the putative
      PfAtg5 (Pf3D7_1430400). PfAtg5 is expressed in all the intraerythrocytic stages
      and partially colocalizes with ER, mitochondria, apicoplast and PfAtg8. It is
      also present on the double membrane bound vesicles. Altogether, these studies
      pave way for the detailed dissection of P. falciparum autophagy machinery and
      insights into molecular and functional characterization of its players for
      developing new therapeutics as antimalarials.

PMID- 30302275
TI  - Inhibition of glioblastoma cell proliferation, invasion, and mechanism of action
      of a novel hydroxamic acid hybrid molecule.
AB  - Glioblastoma multiforme is one of the most aggressive brain tumors and current
      therapies with temozolomide or suberoylanilide hydroxamic acid (SAHA, vorinostat)
      show considerable limitations. SAHA is a histone deacetylase (HDAC) inhibitor
      that can cause undesirable side effects due to the lack of selectivity. We show
      here properties of a novel hybrid molecule, sahaquine, which selectively inhibits
      cytoplasmic HDAC6 at nanomolar concentrations without markedly suppressing class
      I HDACs. Inhibition of HDAC6 leads to significant alpha-tubulin acetylation,
      thereby impairing cytoskeletal organization in glioblastoma cells. The primaquine
      moiety of sahaquine reduced the activity of P-glycoprotein, which contributes to
      glioblastoma multiforme drug resistance. We propose the mechanism of action of
      sahaquine to implicate HDAC6 inhibition together with suppression of epidermal
      growth factor receptor and downstream kinase activity, which are prominent
      therapeutic targets in glioblastoma multiforme. Sahaquine significantly reduces
      the viability and invasiveness of glioblastoma tumoroids, as well as brain tumor
      stem cells, which are key to tumor survival and recurrence. These effects are
      augmented with the combination of sahaquine with temozolomide, the natural
      compound quercetin or buthionine sulfoximine, an inhibitor of glutathione
      biosynthesis. Thus, a combination of agents disrupting glioblastoma and brain
      tumor stem cell homeostasis provides an effective anti-cancer intervention.

PMID- 30302276
TI  - Metabolic profile and differentiation potential of extraembryonic endoderm-like
      cells.
AB  - Glucose metabolism has a crucial role for providing substrates required to
      generate ATP and regulate the epigenetic landscape. We reported that F9 embryonal
      carcinoma stem-like cells require cytosolic reactive oxygen species to
      differentiate into extraembryonic endoderm; however, mitochondrial sources were
      not examined. To extend these studies, we examined the metabolic profile of early
      and late-passage F9 cells, and show that their ability to differentiate is
      similar, even though each population has dramatically different metabolic
      profiles. Differentiated early-passage cells relied on glycolysis, while
      differentiated late-passage cells transitioned towards oxidative phosphorylation
      (OXPHOS). Unexpectedly, electron transport chain protein stoichiometry was
      disrupted in differentiated late-passage cells, whereas genes encoding mitofusion
      1 and 2, which promote mitochondrial fusion and favor OXPHOS, were upregulated in
      differentiated early-passage cells. Despite this, early-passage cells cultured
      under conditions to promote glycolysis showed enhanced differentiation, whereas
      promoting OXPHOS in late-passage cells showed a similar trend. Further analysis
      revealed that the distinct metabolic profiles seen between the two populations is
      largely associated with changes in genomic integrity, linking metabolism to
      passage number. Together, these results indicate that passaging has no effect on
      the potential for F9 cells to differentiate into extraembryonic endoderm;
      however, it does impact their metabolic profile. Thus, it is imperative to
      determine the molecular and metabolic status of a stem cell population before
      considering its utility as a therapeutic tool for regenerative medicine.

PMID- 30302278
TI  - YL064 directly inhibits STAT3 activity to induce apoptosis of multiple myeloma
      cells.
AB  - Aberrant activation of signal transducer and activator of transcription 3 (STAT3)
      plays a critical role in the proliferation and survival of multiple myeloma. And
      inactivation of STAT3 is considered a promising strategy for the treatment of
      multiple myeloma. Here we show that the sinomenine derivative YL064 could
      selectively reduce the cell viability of multiple myeloma cell lines and primary
      multiple myeloma cells. Moreover, YL064 also induces cell death of myeloma cells
      in the presence of stromal cells. Western blot analysis showed that YL064
      inhibited the constitutive activation and IL-6-induced activation of STAT3,
      reflected by the decreased phosphorylation of STAT3 on Tyr705. Consistent with
      this, YL064 inhibited the nuclear translocation of STAT3 and the expression of
      STAT3 target genes, such as cyclin D1 and Mcl-1. Using biotin- and FITC-labeled
      YL064, we found that YL064 could pull-down STAT3 from myeloma cells and
      colocalized with STAT3, suggesting that YL064 directly targets STAT3. Cellular
      thermal shift assay further demonstrated the engagement of YL064 to STAT3 in
      cells. Molecular docking studies indicated that YL064 may interact with STAT3 in
      its SH2 domain, thereby inhibiting the dimerization of STAT3. Finally, YL064
      inhibited the growth of human myeloma xenograft in vivo. Taken together, this
      study demonstrated that YL064 may be a promising candidate compound for the
      treatment of multiple myeloma by directly targeting STAT3.

PMID- 30302280
TI  - Selective toxicity of tumor treating fields to melanoma: an in vitro and in vivo
      study.
AB  - Tumor treating fields (TTFs) are a newly developed cancer therapy technology
      using an alternating electric field that may be a possible candidate for
      overcoming the limitations of conventional treatment methods currently used in
      cancer treatment. Although clinical results using TTFs appear promising, concerns
      regarding side effects must be clarified to demonstrate the effectiveness of this
      treatment method. To investigate the side effects of TTF treatment, the damage to
      normal cell lines and normal tissue of a mouse model was compared with the damage
      to tumor cells and tumors in a mouse model after TTF treatment. No serious damage
      was found in the normal cells and normal tissues of the mouse model, suggesting
      that the side effects of TTF treatment may not be serious. Our evidence based on
      in vitro and in vivo experiments suggests that TTF may cause selective damage to
      cancer cells, further demonstrating the potential of TTF as an attractive
      alternative to conventional cancer treatment modalities.

PMID- 30302281
TI  - A combination of TLR-4 agonist and saponin adjuvants increases antibody diversity
      and protective efficacy of a recombinant West Nile Virus antigen.
AB  - Members of the Flaviviridae family are the leading causes of mosquito-borne viral
      disease worldwide. While dengue virus is the most prevalent, the recent Zika
      virus outbreak in the Americas triggered a WHO public health emergency, and
      yellow fever and West Nile viruses (WNV) continue to cause regional epidemics.
      Given the sporadic nature of flaviviral epidemics both temporally and
      geographically, there is an urgent need for vaccines that can rapidly provide
      effective immunity. Protection from flaviviral infection is correlated with
      antibodies to the viral envelope (E) protein, which encodes receptor binding and
      fusion functions. TLR agonist adjuvants represent a promising tool to enhance the
      protective capacity of flavivirus vaccines through dose and dosage reduction and
      broadening of antiviral antibody responses. This study investigates the ability
      to improve the immunogenicity and protective capacity of a promising clinical
      stage WNV recombinant E-protein vaccine (WN-80E) using a novel combination
      adjuvant, which contains a potent TLR-4 agonist and the saponin QS21 in a
      liposomal formulation (SLA-LSQ). Here, we show that, in combination with WN-80E,
      optimized SLA-LSQ is capable of inducing long-lasting immune responses in
      preclinical models that provide sterilizing protection from WNV challenge,
      reducing viral titers following WNV challenge to undetectable levels in Syrian
      hamsters. We have investigated potential mechanisms of action by examining the
      antibody repertoire generated post-immunization. SLA-LSQ induced a more diverse
      antibody response to WNV recombinant E-protein antigen than less protective
      adjuvants. Collectively, these studies identify an adjuvant formulation that
      enhances the protective capacity of recombinant flavivirus vaccines.

PMID- 30302279
TI  - Zebrafish: an emerging real-time model system to study Alzheimer's disease and
      neurospecific drug discovery.
AB  - Zebrafish (Danio rerio) is emerging as an increasingly successful model for
      translational research on human neurological disorders. In this review, we
      appraise the high degree of neurological and behavioural resemblance of zebrafish
      with humans. It is highly validated as a powerful vertebrate model for
      investigating human neurodegenerative diseases. The neuroanatomic and
      neurochemical pathways of zebrafish brain exhibit a profound resemblance with the
      human brain. Physiological, emotional and social behavioural pattern similarities
      between them have also been well established. Interestingly, zebrafish models
      have been used successfully to simulate the pathology of Alzheimer's disease (AD)
      as well as Tauopathy. Their relatively simple nervous system and the optical
      transparency of the embryos permit real-time neurological imaging. Here, we
      further elaborate on the use of recent real-time imaging techniques to obtain
      vital insights into the neurodegeneration that occurs in AD. Zebrafish is adeptly
      suitable for Ca2+ imaging, which provides a better understanding of neuronal
      activity and axonal dystrophy in a non-invasive manner. Three-dimensional imaging
      in zebrafish is a rapidly evolving technique, which allows the visualisation of
      the whole organism for an elaborate in vivo functional and neurophysiological
      analysis in disease condition. Suitability to high-throughput screening and
      similarity with humans makes zebrafish an excellent model for screening
      neurospecific compounds. Thus, the zebrafish model can be pivotal in bridging the
      gap from the bench to the bedside. This fish is becoming an increasingly
      successful model to understand AD with further scope for investigation in
      neurodevelopment and neurodegeneration, which promises exciting research
      opportunities in the future.

PMID- 30302282
TI  - AS03-adjuvanted H5N1 vaccine promotes antibody diversity and affinity maturation,
      NAI titers, cross-clade H5N1 neutralization, but not H1N1 cross-subtype
      neutralization.
AB  - Immune responses to inactivated vaccines against avian influenza are poor due in
      part to lack of immune memory. Adjuvants significantly increased virus
      neutralizing titers. We performed comprehensive analyses of polyclonal antibody
      responses following FDA-approved adjuvanted H5N1-A/Indonesia vaccine,
      administered in presence or absence of AS03. Using Whole Genome Fragment Phage
      Display Libraries, we observed that AS03 induced antibody epitope diversity to
      viral hemagglutinin (HA) and neuraminidase compared with unadjuvanted vaccine.
      Furthermore, AS03 promoted significant antibody affinity maturation to properly
      folded H5-HA1 (but not to HA2) domain, which correlated with neutralization
      titers against both vaccine and heterologous H5N1 strains. However, no increase
      in heterosubtypic cross-neutralization of Group1-H1N1 seasonal strains was
      observed. AS03-H5N1 vaccine also induced higher neuraminidase inhibition antibody
      titers. This study provides insight into the differential impacts of AS03
      adjuvant on H5N1 vaccine-induced antibody responses that may help optimize
      vaccine platforms for future vaccines with improved protection against seasonal
      and pandemic influenza strains.

PMID- 30302283
TI  - System immunology-based identification of blood transcriptional modules
      correlating to antibody responses in sheep.
AB  - Inactivated vaccines lack immunogenicity and therefore require potent adjuvants.
      To understand the in vivo effects of adjuvants, we used a system immunology-based
      analysis of ovine blood transcriptional modules (BTMs) to dissect innate immune
      responses relating to either antibody or haptoglobin levels. Using inactivated
      foot-and-mouth disease virus as an antigen, we compared non-adjuvanted to
      liposomal-formulated vaccines complemented or not with TLR4 and TLR7 ligands.
      Early after vaccination, BTM relating to myeloid cells, innate immune responses,
      dendritic cells, and antigen presentation correlated positively, whereas BTM
      relating to T and natural killer cells, as well as cell cycle correlated
      negatively with antibody responses. Interestingly, similar BTM also correlated
      with haptoglobin, but in a reversed manner, indicating that acute systemic
      inflammation is not beneficial for early antibody responses. Analysis of vaccine
      dependent BTM modulation showed that liposomal formulations induced similar
      responses to those correlating to antibody levels. Surprisingly, the addition of
      the TLR ligands appeared to reduce early immunological perturbations and mediated
      anti-inflammatory effects, despite promoting antibody responses. When pre
      vaccination BTM were analyzed, we found that high vaccine responders expressed
      higher levels of many BTM relating to cell cycle, antigen-presenting cells, and
      innate responses as compared with low responders. In conclusion, we have
      transferred human BTM to sheep and identified early vaccine-induced responses
      associated with antibody levels or unwanted inflammation in a heterogeneous and
      small group of animals. Such readouts are applicable to other veterinary species
      and very useful to identify efficient vaccine adjuvants, their mechanism of
      action, and factors related to low responders.

PMID- 30302284
TI  - Overcoming immunogenicity issues of HIV p24 antigen by the use of innovative
      nanostructured lipid carriers as delivery systems: evidences in mice and non
      human primates.
AB  - HIV is one of the deadliest pandemics of modern times, having already caused 35
      million deaths around the world. Despite the huge efforts spent to develop
      treatments, the virus cannot yet be eradicated and continues to infect new
      people. Spread of the virus remains uncontrolled, thus exposing the worldwide
      population to HIV danger, due to the lack of efficient vaccines. The latest
      clinical trials describe the challenges associated with developing an effective
      prophylactic HIV vaccine. These immunological obstacles will only be overcome by
      smart and innovative solutions applied to the design of vaccine formulations.
      Here, we describe the use of nanostructured lipid carriers (NLC) for the delivery
      of p24 protein as a model HIV antigen, with the aim of increasing its
      immunogenicity. We have designed vaccine formulations comprising NLC grafted with
      p24 antigen, together with cationic NLC optimized for the delivery of
      immunostimulant CpG. This tailored system significantly enhanced immune responses
      against p24, in terms of specific antibody production and T-cell activation in
      mice. More importantly, the capacity of NLC to induce specific immune responses
      against this troublesome HIV antigen was further supported by a 7-month study on
      non-human primates (NHP). This work paves the way toward the development of a
      future HIV vaccine, which will also require the use of envelope antigens.

PMID- 30302285
TI  - Malaria vaccine candidate based on Duffy-binding protein elicits strain
      transcending functional antibodies in a Phase I trial.
AB  - Reticulocyte invasion by Plasmodium vivax requires interaction of the Duffy
      binding protein (PvDBP) with host Duffy antigen receptor for chemokines (DARCs).
      The binding domain of PvDBP maps to a cysteine-rich region referred to as region
      II (PvDBPII). Blocking this interaction offers a potential path to prevent P.
      vivax blood-stage growth and P. vivax malaria. This forms the rationale for
      development of a vaccine based on PvDBPII. Here we report results of a Phase I
      randomized trial to evaluate the safety and immunogenicity of recombinant PvDBPII
      formulated with glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE). Thirty
      six malaria-naive, healthy Indian male subjects aged 18-45 years were assigned
      into three cohorts corresponding to doses of 10, 25 and 50 ug of PvDBPII
      formulated with 5 ug of GLA-SE. Each cohort included nine PvDBPII/GLA-SE
      vaccinees and three hepatitis B control vaccine recipients. Each subject received
      the assigned vaccine intramuscularly on days 0, 28 and 56, and was followed up
      till day 180. No serious AE was reported and PvDBPII/GLA-SE was well-tolerated
      and safe. Analysis by ELISA showed that all three doses of PvDBPII elicited
      antigen-specific binding-inhibitory antibodies. The 50 ug dose elicited
      antibodies against PvDBPII that had the highest binding-inhibitory titres and
      were most persistent. Importantly, the antibody responses were strain
      transcending and blocked receptor binding of diverse PvDBP alleles. These results
      support further clinical development of PvDBPII/GLA-SE to evaluate efficacy
      against sporozoite or blood-stage challenge in controlled human malaria infection
      (CHMI) models and against natural P. vivax challenge in malaria endemic areas.

PMID- 30302286
TI  - The Relationship between Inter-Arm Blood Pressure Difference and Coronary Artery
      Disease Severity Calculated by the SYNTAX Score.
AB  - Objectives: The inter-arm systolic blood pressure difference (IASBPD) is closely
      related to cardiovascular mortality and morbidity. The SYNTAX score indicates the
      extent and complexity of coronary artery disease, which are determined by
      coronary angiography. The aim of our study is to examine the relationship between
      the IASBPD (which is easily calculated in routine practice) and the SYNTAX score.
      Methods: 104 patients were included in this cross-sectional study. The IASBPD was
      calculated by blood pressure measurements obtained simultaneously from both arms.
      The SYNTAX score was calculated by coronary angiography. Results: Patients were
      divided into two groups: those with a high SYNTAX score (>=20) and those with a
      low SYNTAX score (<20). The mean IASBPD values were significantly higher in the
      group with a high SYNTAX score (>=20) (p<0.001). The patients with IASBPD>=10
      were more likely to have a high SYNTAX score compared to the patients with
      IASBPD<10 (p<0.001). Multiple logistic regression analysis revealed that only the
      IASBPD values were found to be independently associated with high SYNTAX score
      (OR: 1.717 (CI: 1.307-2.257), p<0.001). Conclusion: The IASBPD values obtained by
      only blood pressure measurements are closely related to the extent of coronary
      artery disease.

PMID- 30302287
TI  - Efficacy of an Anthocyanin and Prebiotic Blend on Intestinal Environment in Obese
      Male and Female Subjects.
AB  - Background: Anthocyanins and prebiotics impact overall health and wellness,
      likely through modulation of the microbiota and the intestinal ecosystem.
      Objectives: An 8-week open-label study in male and female volunteers with
      uncomplicated obesity was designed to study the efficacy of an anthocyanin and
      prebiotic blend in modulating intestinal microbiota and intestinal inflammation.
      Results: After 8 weeks of daily supplementation, participants had a significant
      decrease in Firmicutes (p < 0.001) and Actinobacteria (p < 0.001) and a
      significant increase in Bacteroidetes (p < 0.001). Bowel habits were improved as
      evidenced by reductions in the severity of bloating (p < 0.05), gas (p=0.035),
      and abdominal pain (p=0.015) as well as significant improvements in stool
      consistency (p < 0.05). Finally, a nonsignificant decrease in the inflammatory
      marker fecal calprotectin was seen (p=0.107). The supplement was safe and well
      tolerated. Conclusions: The results suggest that regular consumption of the
      anthocyanin-prebiotic blend positively modulated the intestinal ecosystem and
      provided insights into the mechanisms of action and its impact on health
      benefits.

PMID- 30302288
TI  - Current Innovations in Peripheral Nerve Stimulation.
AB  - Peripheral nerve stimulation has been used in the treatment of several chronic
      pain conditions including pain due to peripheral nerve dysfunctions, complex
      regional pain syndrome, and cranial neuralgias. It has been shown to be effective
      for chronic, intractable pain that is refractory to conventional therapies such
      as physical therapy, medications, transcutaneous electrical stimulations, and
      nerve blocks. Recently, a new generation of peripheral nerve stimulation devices
      has been developed; these allow external pulse generators to transmit impulses
      wirelessly to the implanted electrode, and their implantation is significantly
      less invasive. In this review, we discuss the history, pathophysiology,
      indications, implantation process, and outcomes of employing peripheral nerve
      stimulation to treat chronic pain conditions.

PMID- 30302290
TI  - The Impact of Scientific and Technical Training on Improving Routine Collection
      of Antenatal Care Data for Maternal and Foetal Risk Assessment: A Case Study in
      the Province of South Kalimantan, Indonesia.
AB  - Objectives: First, to assess the impact of scientific and technical training on
      midwives' abilities in collecting and recording the results of routine antenatal
      care examinations. Second, to explore midwives' views with regard to factors
      affecting their abilities to successfully complete the data documentation tasks.
      Methods: The study was conducted in South Kalimantan, Indonesia (April 2016
      October 2017). Nineteen urban and rural midwives were selected. Access to
      antenatal care information on 4,946 women (retrospective cohort study) and 381
      women (prospective cohort study) was granted. A descriptive and exploratory
      design was used to describe midwives' abilities and challenges pertaining to
      timely collection and recording of results concerning antenatal care
      examinations. Results: Scientific and technical training has significantly
      improved the average amount of recorded antenatal care data (from 17.5% to 62.1%,
      p-value < 0.0005). Lack of awareness, high workload, and insufficient skills and
      facilities are the main reasons for the database gaps. Conclusions: The training
      has equipped midwives with scientific knowledge and technical abilities to allow
      routine collection of antenatal care data. Provision and adequate use of this
      information during different stages of pregnancy is crucial as an evidence-based
      guideline to assess maternal and foetal risk factors to ending preventable
      mortality.

PMID- 30302291
TI  - Stochastic Resonance Training Improves Balance and Musculoskeletal Well-Being in
      Office Workers: A Controlled Preventive Intervention Study.
AB  - Sixty-two office workers in a Swiss federal department were randomly assigned to
      a training and a control group. While the training group was instructed to
      complete 3 stochastic resonance whole-body vibration (SR-WBV) exercises every
      week for 4 weeks, the control group received no treatment. During this time all
      participants answered a daily questionnaire concerning their surefootedness,
      sense of balance, musculoskeletal well-being, and muscle relaxation. Before and
      after the 4-week SR-WBV intervention, balance was tested with a single-leg stance
      on a foam mat of the Balance Error Scoring System (BESS) using a SwayStarTM
      System measuring Total Angle Area (TotAngArea) and Total Velocity Area
      (TotVelArea). Multilevel results highlighted a significant increase over time for
      surefootedness and sense of balance (t = 2.491, p = .016), as well as for
      musculoskeletal well-being and muscle relaxation (t = 2.538, p = .014) in the
      training group but not in the control group. Balance tests showed improvement of
      balance in the training group (TotAngArea: Z = 2.550, p = .011; TotVelArea: Z =
      3.334, p = .001) but not in the control group. SR-WBV exercise indicated a high
      compliance during this study (3.87+/-0.45 trainings per week) underlining its
      benefits for the working context. Especially office workers who spend most of
      their time in sitting position could profit from SR-WBV exercise to improve
      balance and reduce the risk of falls.

PMID- 30302292
TI  - Osseointegrated Transcutaneous Device for Amputees: A Pilot Large Animal Model.
AB  - Traditional above-the-knee amputation prosthetics utilize a stump-socket
      interface that is well-known for skin/socket problems, sitting difficulty, disuse
      osteopenia, and increased work of ambulation. As a result, we evaluated a novel
      osseointegrated transcutaneous implant in a large animal. The implant was
      designed to promote osseointegration at the bone-implant interface and minimize
      complications. As proof of concept, four Dorset sheep underwent a two-stage
      surgery for forelimb placement of an osseointegrated transcutaneous implant
      utilizing Compress(r) technology (Biomet, Inc., Warsaw, IN). Two sheep received a
      long anchor plug (90 mm long x 9 mm in diameter) and two received a short anchor
      plug (46 mm long x 9 mm in diameter). Sixteen weeks after the initial surgery,
      the operative limbs, along with the attached implant, underwent radiographic and
      histological analysis for osseointegration. Periprosthetic fractures occurred in
      the two animals that received the longer internal prosthesis; one healed with
      splinting and the other animal underwent a second surgical procedure to advance
      the amputation site more proximal. No fractures occurred in the shorter internal
      prosthesis group. There was no histological evidence of infection and none of the
      transcutaneous adapters failed. Bone-implant osseointegration was demonstrated in
      two of three limbs that underwent histological analysis. This unique implant
      demonstrated osseointegration without transcutaneous adapter failure, all while
      displaying minimal infection risk from the outside environment. Although it
      involved short-term follow-up in a limited number of animals, this pilot study
      provides a platform for further investigation into the valid concept of using
      Compress(r) technology as an endo-exo device.

PMID- 30302289
TI  - Crystallography and Its Impact on Carbonic Anhydrase Research.
AB  - X-ray and neutron crystallography are powerful techniques utilized to study the
      structures of biomolecules. Visualization of enzymes in complex with
      substrate/product and the capture of intermediate states can be related to
      activity to facilitate understanding of the catalytic mechanism. Subsequent
      analysis of small molecule binding within the enzyme active site provides insight
      into mechanisms of inhibition, supporting the design of novel inhibitors using a
      structure-guided approach. The first X-ray crystal structures were determined for
      small, ubiquitous enzymes such as carbonic anhydrase (CA). CAs are a family of
      zinc metalloenzymes that catalyze the hydration of CO2, producing HCO3 - and a
      proton. The CA structure and ping-pong mechanism have been extensively studied
      and are well understood. Though the function of CA plays an important role in a
      variety of physiological functions, CA has also been associated with diseases
      such as glaucoma, edema, epilepsy, obesity, and cancer and is therefore
      recognized as a drug target. In this review, a brief history of crystallography
      and its impact on CA research is discussed.

PMID- 30302293
TI  - Primary Carnitine Deficiency: A Rare, Reversible Metabolic Cardiomyopathy.
AB  - A 24-year-old female with a diagnosis of primary carnitine deficiency, a rare
      inherited metabolic disorder predominantly described in the paediatric literature
      that causes cardiomyopathy, presented for evaluation after three months of
      nonadherence with prescribed carnitine therapy. Initial echocardiography
      demonstrated severe left ventricular dilation (104 ml/m2) (normal < 76 ml/m2)
      with moderate systolic dysfunction (ejection fraction 40%) and severe right
      ventricular dilation with mild systolic dysfunction. Carnitine replacement was
      commenced, and a cardiac magnetic resonance imaging (MRI) performed five days
      later demonstrated dramatic improvement in biventricular function with
      normalization of left and right ventricular systolic function. To our knowledge,
      this is only the second case describing the rapid reversal of cardiomyopathy in
      an adult patient with this rare condition.

PMID- 30302294
TI  - A Novel Double Side Branch Protection Technique for a Left Main Trifurcation
      Lesion: Simultaneous Jailed Balloon and Jailed Corsair Technique.
AB  - Percutaneous coronary intervention for left main trifurcation disease is
      challenging. Although side branch protection techniques such as the jailed
      balloon technique and jailed Corsair technique are the established methods for
      treatment of coronary bifurcation lesions, little is known regarding the
      application and feasibility of these techniques for left main trifurcation
      disease. We herein describe a 72-year-old man with angina pectoris who was
      successfully treated with percutaneous coronary stent implantation for a left
      main trifurcation lesion. In this case, we performed a novel double side branch
      protection technique, the simultaneous jailed balloon and jailed Corsair
      technique, with a single 8 Fr guiding catheter. This is the first case report to
      highlight the feasibility and efficacy of combined use of the jailed balloon and
      jailed Corsair techniques during percutaneous coronary intervention for left main
      trifurcation disease.

PMID- 30302295
TI  - Successful Treatment of Severe Type B Lactic Acidosis in a Patient with HIV/AIDS
      Associated High-Grade NHL.
AB  - Type B lactic acidosis is a rare metabolic complication sometimes associated with
      hematologic malignancies. When present, this type of lactic acidosis is most
      commonly seen in patients with high-grade lymphomas or leukemias and is usually
      indicative of a dismal prognosis. We report a case of a 27-year man with acquired
      immunodeficiency syndrome (AIDS) that presented with bilateral lower extremity
      swelling, an abdominal mass, and weight loss. His lab values showed elevated
      anion gap with lactic acidosis and computed tomography (CT) of the abdomen showed
      a large soft-tissue mass arising from the left hepatic lobe. Biopsy of the
      abdominal mass demonstrated a high-grade diffuse large B-cell lymphoma. The
      patient's lactic acidosis resolved after starting chemotherapy, and a complete
      response was evident on PET-CT after a third cycle of rituximab, etoposide,
      prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOC-RR). Care-givers
      should be aware of the implications of lactic acidosis associated with malignancy
      and the need for prompt diagnosis and treatment.

PMID- 30302296
TI  - A Case of Intrathoracic Gastric Duplication Cyst Detected on Prenatal Ultrasound
      Examination.
AB  - A 37-year-old (G4P3) woman was referred to our hospital at 32 weeks of gestation
      for the evaluation of a fetus with an intrathoracic cystic lesion.
      Ultrasonography and magnetic resonance imaging revealed that a fetal cystic
      lesion without a mucosal layer was located in the posterior mediastinum. These
      findings were consistent with a bronchogenic cyst. At 38 3/7 weeks of gestation,
      an elective cesarean section was performed because of her previous cesarean
      section. A female neonate without any external anomalies, weighing 2,442 g, with
      Apgar scores of 8 and 9, and requiring no resuscitation was born. Four weeks
      after delivery, the neonate was admitted because of respiratory distress due to
      mass effect. At right lateral thoracotomy, a 105 * 65 mm of solitary smooth
      walled cyst containing serosanguineous fluid was found in the posterior
      mediastinum, which was excised completely. Histologic examination revealed the
      diagnosis of the mediastinal gastric duplication cyst. The neonate made an
      uneventful recovery. Accurate diagnosis is not necessary, but detection and
      continuous observation are logical. Although gastric duplication, particularly
      intrathoracic, is a rare pathology, it should be considered in the differential
      diagnosis of any intrathoracic cyst.

PMID- 30302298
TI  - Assessment and Retrieval of Aspirated Tracheoesophageal Prosthesis in the
      Ambulatory Setting.
AB  - Tracheoesophageal prosthesis (TEP) is the most common voice restoration method
      following total laryngectomy. Prosthesis extrusion and aspiration occurs in 3.9%
      to 6.7% and causes dyspnea. Emergency centers are unfamiliar with management of
      the aspirated TEP. Prior studies report removal of aspirated TEP prostheses under
      general anesthesia. Laryngectomees commonly have poor pulmonary function, posing
      increased risks for complications of general anesthesia. We present a
      straightforward approach to three cases of aspirated TEP prosthesis removed in
      the ambulatory setting. In each case, aspirated TEP was diagnosed with flexible
      bronchoscopy under local anesthesia at the time of consultation, and all
      prostheses were retrieved atraumatically using a biopsy grasper forceps inserted
      via the side channel of the bronchoscope. The aspirated TEP prosthesis can be
      safely and efficiently removed via bedside bronchoscopy.

PMID- 30302297
TI  - Breakage in Two Points of a Short and Undersized "Affixus" Cephalomedullary Nail
      in a Very Active Elderly Female: A Case Report and Review of the Literature.
AB  - Introduction: Trochanteric fractures of the femur are common in elderly
      individuals with osteoporosis. The use of cephalomedullary nails is increasing,
      and they are now the most commonly used fixation devices, especially for the
      treatment of unstable trochanteric fractures. The nail breakage is not the most
      common complication of intramedullary nailing. Many scientific papers report nail
      breakage in a specific location: through the lag screw hole, the nail shaft, or
      the distal locking hole. Materials and Methods: We present a case of an 84-year
      old patient treated with modular revision hip arthroplasty due to the breakage in
      two points of a cephalomedullary nail implanted 3 years earlier for a
      subtrochanteric fracture. Results: After modular revision hip arthroplasty, the
      functional results and quality of life have been excellent. Conclusions: As far
      as we could determine, this appears to be the first case of a breakage of a
      cephalomedullary nail in two points after nonunion in a very active elderly
      female.

PMID- 30302299
TI  - Two Cases of Sinonasal Non-Intestinal-Type Adenocarcinoma with Squamoid Morules
      Expressing Nuclear beta-Catenin and CDX2: A Curious Morphologic Finding Supported
      by Molecular Analysis.
AB  - Sinonasal non-intestinal-type adenocarcinoma (non-ITAC) is a rare,
      morphologically diverse neoplasm of the head and neck. Squamoid morular
      metaplasia has recently been reported as an occasional finding in non-ITAC.
      Interestingly, these squamoid morules often show aberrant expression of CDX2 as
      well as nuclear expression of beta-catenin, similar to other tumors that show
      this type of metaplasia, but the underlying mechanism responsible for this
      finding is not completely understood. We present two cases of low-grade non-ITAC
      with squamoid morules coexpressing CDX2 and nuclear beta-catenin by
      immunohistochemistry, both of which were found to harbor a mutation in CTNNB1,
      the gene encoding beta-catenin. This finding provides support that an alteration
      in the beta-catenin pathway, including mutations in the beta-catenin gene itself,
      is responsible for this recently described morphologic phenomenon in non-ITAC.

PMID- 30302300
TI  - Determination of Phosphorus in Soil by ICP-OES Using an Improved Standard
      Addition Method.
AB  - In this study, an improved standard addition method (ISAM) was developed for the
      determination of phosphorus in soil by ICP-OES based on the conventional standard
      addition method (CSAM) and calibration curve method (CCM). Certified standard
      soils were analyzed by the proposed ISAM method. The values obtained by ISAM
      method agreed with the certified values. Additionally, the results obtained by
      ISAM method were compared with those determined by the other two methods (CSAM
      and CCM). All the values obtained by the ISAM agreed with those from the other
      two methods. The detection limit, quantification limit, and recovery rate of each
      method were calculated, and the recovery rates of soil samples and the blank were
      all within the range of 90%-110%. Finally, the proposed method was applied to
      determine phosphorous in soil samples from Guangnan County, Yunnan Province,
      China, and the meadow soil from Qinghai-Tibet Plateau, China. The relative errors
      between the results from ISAM and CCM were all within 10%, and t-test showed that
      the results between ISAM and CCM had no significant difference (P > 0.05).
      Therefore, the proposed method overcame the matrix effect in some extent and was
      an acceptable method for the rapid and accurate batch analysis of P content in
      soil sample, especially batch samples with obvious matrix effect.

PMID- 30302302
TI  - Construction of the Pentacyclic Core and Formal Total Synthesis of (rac)
      Renieramycin T.
AB  - Invited for this month's cover picture is the group of Professor Naoki Saito at
      the Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University
      (Japan). They achieved the first total synthesis of renieramycin T in 2016, and
      they have been following an alternative route to supply a large amount of it in
      order to promote research of the next stage, such as structure-activity
      relationship studies. This paper reports a formal total synthesis in 21 steps
      from a known piperazine-2,5-dione derivative. The key step of this synthesis is
      the modified Pictet-Spengler cyclization of a primary amine with an oxomalonic
      acid ester derivative followed by decarboxylation, and stereo-controlled
      protonation at C-1 position of the enol intermediate from the less-hindered face.
      Read the full text of their Full Paper at https://doi.org/10.1002/open.201800112.

PMID- 30302301
TI  - A Dorsal Approach for Ulnar Shortening Osteotomy.
AB  - Aim  This study aims to evaluate the long-term complications, results, and
      patient satisfaction rates of a dorsally approached ulnar shortening osteotomy
      for ulnar impaction syndrome. Methods  A retrospective chart review of 20
      patients was performed. Primary outcomes of interest were subjective, measured
      using the Patient-Rated Wrist Evaluation (PRWE) score, Disability of the Arm,
      Shoulder, and Hand (DASH) score, and the third questionnaire about patient
      satisfaction, composed by the authors. Secondary outcomes included hardware
      removal due to irritation and other complications. Results  Mean postoperative
      functional score of PRWE was 28 (standard deviation [SD], 30) and DASH 20 (SD,
      26), respectively. Fifteen patients were satisfied with the operation. Removal of
      hardware was noted in six patients. In one patient plate breakage occurred.
      Conclusion  Similar postoperative functional scores and complications were seen
      in patients undergoing an ulnar shortening osteotomy with a dorsally placed plate
      for ulnar impaction syndrome, compared with other plate placement localizations.
      The incidence of plate removal is also comparable to previously described
      results. As the dorsally placed plate and freehand technique, are relatively
      easy, we feel that it has a place in the treatment of ulnar impaction syndrome.
      Level of Evidence  Level IV, retrospective cohort study.

PMID- 30302303
TI  - Spaced TiO2 Nanotubes Enable Optimized Pt Atomic Layer Deposition for Efficient
      Photocatalytic H2 Generation.
AB  - In the present work, we report the use of TiO2 nanotube (NT) layers with a
      regular intertube spacing that are decorated by Pt nanoparticles through the
      atomic layer deposition (ALD) of Pt. These Pt-decorated spaced (SP) TiO2 NTs are
      subsequently explored for photocatalytic H2 evolution and are compared to
      classical close-packed (CP) TiO2 NTs that are also decorated with various amounts
      of Pt by using ALD. On both tube types, by varying the number of ALD cycles, Pt
      nanoparticles of different sizes and areal densities are formed, uniformly
      decorating the inner and outer walls from tube top to tube bottom. The
      photocatalytic activity for H2 evolution strongly depends on the size and density
      of Pt nanoparticles, driven by the number of ALD cycles. We show that, for SP
      NTs, a much higher photocatalytic performance can be achieved with significantly
      smaller Pt nanoparticles (i.e. for fewer ALD cycles) compared to CP NTs.

PMID- 30302304
TI  - Giant Calvarial Ewing's Sarcoma: A Case Report.
AB  - Ewing's sarcoma (EWS) is the second most common primary bone tumor seen in
      children and adolescents, first being osteosarcoma. Skull lesions are seen in 6
      to 9% of cases. The tumor tends to reside most frequently on frontal and parietal
      bones. In the literature, majority of papers on calvarial EWS present cases with
      intracranial involvement; extracranial extension is reported in only eight cases.
      The case that we are presenting in this report is a 23-year-old male patient with
      multiple infiltrations in femur, costal bones, and calvarium which had been
      diagnosed radiologically and histopathologically as EWS. The calvarial metastasis
      had reached a very huge size with dimensions of approximately 7.5 * 7.5 * 9.5 cm
      and was successfully excised totally. Twelve months of follow-up revealed no
      recurrence in the surgical site showing that total removal of giant cranial EWS
      may improve morbidity of these patients.

PMID- 30302305
TI  - Evaluation of the styloid process in a Sri Lankan population using digital
      panoramic radiographs.
AB  - Objective: The objectives of this study were to evaluate the normal radiographic
      length of the styloid process (SP), prevalence and type of elongation, and
      angulation of the styloid process in relation to sex and side on digital
      panoramic radiographs in a Sri Lankan population. Methods: A total of 100 digital
      panoramic images selected from the database at the Division of Oral Medicine and
      Radiology, Faculty of Dental Sciences, University of Peradeniya, Sri Lanka were
      evaluated for the radiological features of the styloid process. Lengths greater
      than 30 mm were consider as elongated. Elongated styloid processes were also
      classified into three types based on Langlais classification (elongated, pseudo
      articulated; and segmented). Results: The mean radiological length of the SP on
      the right and left side was 25.8 mm +/- 7.5 mm and 23.2 mm +/- 9.0 mm
      respectively. The prevalence of elongated styloid process in males and female
      were 34.9% and 24.6%. The maximum length observed on right and left sides were
      43.2 mm and 41 mm respectively. However, the differences between the genders and
      the sides were statistically not significant (P = 0.199). The most frequently
      observed type of elongation was type I (elongated) according to the Langlais
      classification. Conclusion: This study provides valuable knowledge of the
      anatomical variations of the SP which may help clinicians from various
      specialties to diagnose the Eagle syndrome.

PMID- 30302306
TI  - A case of disseminated tuberculosis mimicking metastatic cancer.
AB  - Background: Disseminated tuberculosis (TB) or miliary TB is defined as
      lymphohematogenous dissemination of Mycobacterium tuberculosis bacilli, which may
      then affect virtually any organ system. The multiple organ involvement in
      disseminated TB can mimic metastatic cancer and can make the diagnosis
      challenging. False negatives are common therefore repeating microbiologic and
      histologic samples is essential. Case report: We report the case of a young
      immunocompetent patient presenting with multiple atypical extra-pulmonary TB
      involvement. The patient presented with pulmonary, pleural, bilateral testicular
      and multiple bone involvement including calcanerium abscesses. These lesions were
      initially described as metastasis by the radiologist. Therefore lymphoma and
      metastatic testicular cancer as well as TB were high on the differential in this
      young foreign-born male. Pleural, broncho-alveolar lavage, bone marrow and
      cerebrospinal fluid acid-fast bacilli smear and microbiologic culture were all
      negative. However the histologic examination of the trans-bronchial biopsy and
      pleural biopsy showed necrotizing granuloma and helped to narrow down the
      diagnosis. The patient improved with RIPE therapy. Conclusion: This case
      illustrates the diagnostic difficulty of disseminated TB with atypical organ
      involvement. Culture is the gold standard for diagnosing TB but is a long process
      and with 23% of culture negative TB in the United-States, the diagnosis sometimes
      relies on thoroughly ruling-out differential diagnosis and histologic
      examination.

PMID- 30302307
TI  - Successful treatment of steroid-refractory double-positive ANCA and anti-GBM
      disease with a combination of plasma exchange and immunosuppression: A case
      report and literature review.
AB  - The concurrence of antineutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis (AAV) and anti-glomerular basement membrane (GBM) disease, known as
      double-positive disease, is rare, but it occurs at a much higher frequency than
      expected by chance. Double-positive disease has an aggressive clinical course,
      with no optimal treatment strategy. Here we describe a patient with steroid
      refractory double-positive disease who was treated successfully with the addition
      of plasma exchange (PE) and cyclophosphamide (CPA). A 78-year-old Japanese woman
      who was diagnosed with diffuse alveolar hemorrhage and rapidly progressive
      glomerulonephritis received two cycles of pulse steroid therapy. However, her
      respiratory and renal condition deteriorated. She was found to be positive for
      both myeloperoxidase-ANCA and anti-GBM antibodies. The combination of PE and CPA
      improved her systemic condition. This is the first case report of a patient with
      steroid-refractory double-positive disease who was successfully treated with the
      addition of PE and CPA. The marked contrast in therapeutic response to
      corticosteroids alone and the addition of PE and CPA in this case strongly
      implies that earlier induction of combination therapy aimed at rapid removal of
      pathogenic autoantibodies and prevention of ongoing antibody production might
      improve the outcome of this life-threatening disease.

PMID- 30302308
TI  - A unique case report of endobronchial cryptococcosis and review of the
      literature.
AB  - Cryptococcosis is an infection caused by the yeast-like fungus Cryptococcus
      neoformans. Pulmonary cryptococcosis is typically identified as a single mass or
      as multiple nodules, while endobronchial lesions are quite rare. Here we report
      an uncommon case of pulmonary cryptococcosis presenting as endobronchial lesion
      in an immunocompetent patient. A 49-year-old male patient complained of
      intermittent cough with hemoptysis for two years. Computerized tomography of the
      chest showed a filling defect in the basal segment of the right lower lobe
      bronchus. A flexible bronchoscopic examination revealed a white smooth-surfaced
      polypoid lesion completely occluding the medial basal segment of the right lower
      lobe bronchus. The diagnosis was confirmed by bronchial biopsy under
      bronchoscopy, and the histopathologic findings showed the organisms were
      Cryptococcal neoformans. The patient was treated with fluconazole at a dose of
      400 mg daily. The endobronchial lesion was found rapidly diminished after 18 days
      of therapy, and disappeared after 6.5 months of therapy by repeated fiberoptic
      bronchoscopy. Then the patient continued fluconazole for another 2.5 months.
      During the total 16 months' follow-up visits, the patient repeated CT scanning
      for five times, the results of which were all normal. The patient's symptoms
      disappeared as well, and now he is still under follow-up. This case highlights
      the fact that pulmonary cryptococcosis can present as endobronchial lesions even
      in immunocompetent subjects, mimicking lung tumor. Pathological confirmation is
      important to establish the definite diagnosis.

PMID- 30302310
TI  - Prevalence of Capillaria plica in Danish wild carnivores.
AB  - Capillaria plica is a parasitic nematode belonging to the family Capillariidae.
      The adult parasites reside in the urinary tract of wild and domestic canines. The
      infection is most often asymptomatic, but can cause a wide range of symptoms
      including urinary bladder inflammation, pollacisuria, dysuria and hematuria.
      Canines acquire the infection by ingesting the intermediate host, the earthworm
      (Lumbricidae). Epidemiological studies on C. plica infection in wildlife are few
      and only one previous Danish study examined the prevalence in red foxes, while
      studies on prevalence in other animals are limited. We examined the urine
      sediment or urinary bladder from 375 Raccoon dogs (Nyctereutes procyonoides), 247
      red foxes (Vulpes vulpes), 20 beech martens (Martes foina), 16 wild mink
      (Neovison vison), 14 otters (Lutra lutra), nine European polecats (Mustela
      putorius), three European badgers (Meles meles) and one golden jackal (Canis
      aureus) received as a part of Danish wildlife surveillance. Capillaria plica was
      detected in 73.7% of red foxes, 20.0% of beech martens, 0.5% of raccoon dogs, and
      in the Golden jackal. Red foxes originating from all 5 regions of Denmark were
      infected, although with a significantly higher prevalence in the three regions in
      Jutland compared to Region Zealand.

PMID- 30302309
TI  - IgG4-related disease presenting with combined pulmonary fibrosis and emphysema
      (CPFE).
AB  - A 64-year-old man was admitted to our hospital with an abnormal chest shadow. The
      patient was a current-smoker and had a past illness of autoimmune pancreatitis
      with a high serum level of IgG4, 348 mg/dL. Chest CT showed upper-lobe emphysema,
      and lower-lobe reticulation with honeycombing, suggestive of combined pulmonary
      fibrosis with emphysema (CPFE). Surgical lung biopsy was revealed a usual
      interstitial pneumonia pattern with marked infiltration of IgG4-positive plasma
      cells. The patient was diagnosed with IgG4 related disease (IgG4-RD) presenting
      with CPFE. Pulmonary manifestation was improved by corticosteroid therapy. IgG4
      RD may be an underlying condition in patient with CPFE.

PMID- 30302311
TI  - Molecular confirmation of Hymenolepis hibernia in field mice (Apodemus
      sylvaticus) from St Kilda has potential to resolve a host-parasite relationship.
AB  - Insular wildlife populations provide opportunities to examine biological
      questions in systems that are relatively closed and potentially tractable,
      striking examples being the long-term studies of ecology and evolution in the red
      deer and feral sheep populations on the Hebridean islands of Rum and St Kilda. In
      the case of parasitology, Understanding of parasitic infections insular wildlife
      populations in conjunction with knowledge of their origins has the potential to
      add a fresh perspective to disease control in humans and domestic animals. In the
      case of parasitology, understanding infections of insular wildlife populations,
      in conjunction with knowledge of their origins, has the potential to add a fresh
      perspective to disease control in humans and domestic animals. With this in mind,
      gross and molecular examination for the presence of cyclophyllidean tapeworms was
      performed on the viscera and rectal contents of 17 preserved specimens of
      Apodemus sylvaticus field mice and on the naturally voided faeces of a further
      four mice on the remote archipelago of St Kilda. Molecular speciation of
      hexacanth embryos extracted from the faeces of two mice, using nucleotide
      sequence analysis of the ribosomal cytochrome c-oxidase subunit-1, confirmed
      infection with Hymenolepis hibernia. Phylogenetic analysis showed that these were
      genetically distinct from Hymenolepis diminuta, previously reported in the
      insular A. sylvaticus mice, and from other published H. hibernia haplotypes.
      There was insufficient hymenolepidid tapeworm phylogeographic variation to
      resolve the origins of the co-evolved St Kilda mice, primarily due to a lack of
      published H. hibernia Cox-1 sequence data across the parasite's geographical
      range. Nevertheless, the Maximum Likelihood haplotype tree shows the potential
      for molecular parasitology to resolve a host-parasite relationship once more data
      become available. Morphological diagnostic features of zoonotic H. hibernia eggs
      are also described.

PMID- 30302312
TI  - Helminth parasites of alien freshwater fishes in Patagonia (Argentina).
AB  - A survey of the helminth parasites of alien freshwater fishes from Argentinean
      Patagonia is presented, based on samples taken from 2010 to 2017 and including
      previous published records. A total of 1129 fishes were collected, belonging to
      11 species from 7 families. We surveyed 34 localities in 12 river basins, and
      found 43 parasite taxa (15 digeneans, 14 monogeneans, 5 cestodes, 5 nematodes,
      and 4 acanthocephalans), belonging to 22 families. Data are presented as a
      parasite/host list with information on host species and localities, site of
      infection, parasite life-history stage, origin, previous records in Patagonia,
      and accession numbers to vouchers. The most frequently found helminths were
      monogeneans and digeneans. Our data suggest that invading fish in Patagonia have
      transmitted fewer parasite species than they have received by spillback. Twenty
      three (53%) of the parasites seem to be acquired by the exotic fishes from native
      hosts, while 15 helminths were co-introduced along with their exotic fish host
      and continue to parasitize these alien fish but did not invade native hosts; 4 of
      these species were introduced with carp, 3 with Cheirodon interruptus, 3 with
      Corydoras paleatus, 3 with Cnesterodon decemmaculatus, 1 with Oncorhynchus
      tshawytscha, and 1 with Jenynsia multidentata. The majority of these co
      introduced parasites came from the Brazilic ichthyogeographic region (10
      species). This is the first review of helminth parasites of alien fishes in
      Argentina; in total 12 new records of parasites for Argentina, 6 new records of
      parasites for Patagonia, and 29 new host-parasite records are presented here.
      This list is far from complete, however, given that some basins in southern
      Patagonia remain unexplored in terms of parasite detection.

PMID- 30302313
TI  - Bone turnover and bone mineral density in old persons with type 2 diabetes.
AB  - Aims: To understand the paradox of an increased fracture risk despite increased
      bone mineral density (BMD) in persons with type 2 diabetes (DM2). Patients and
      Methods: We studied 80 old persons with DM2. Mineral metabolism, parathyroid
      hormone (PTH), 25-hydroxyvitamin D (25OHD), bone turnover - osteocalcin,
      procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of
      type 1 collagen (CTX) - were measured and BMD was assessed at the lumbar spine
      (LS) and femoral neck (FN). Data was analyzed with the Statistical Package for
      the Social Sciences Program. Results: Low levels of 25OHD (84%) and high values
      of PTH (20%) were found. Osteocalcin was directly related to CTX, p < 0.001, with
      increased bone formation and increased BMD (z-score) at LS and FN. PTH was
      directly related to osteocalcin and CTX and inversely related to BMD at the FN, p
      < 0.05. Patients with dyslipidemia presented higher P1NP, p < 0.05 and patients
      with hypertension presented higher BMD at LS and FN, p < 0.01. Conclusion: Old
      type 2 diabetics present increased bone formation, PTH-driven. Low grade
      secondary hyperparathyroidism may explain the paradox of an increased fracture
      risk despite increased BMD.

PMID- 30302315
TI  - Mechanoreceptor profile of the lateral collateral ligament complex in the human
      elbow.
AB  - Background: Active restraint for the elbow joint is provided by the soft tissue
      component, which consists of a musculoligamentous complex. A lesion of the
      lateral collateral ligament complex (LCLC) is thought to be the primary cause of
      posterolateral rotatory instability in the elbow. Its role as a protective
      reflexogenic structure is supported by the existence of ultrastructural
      mechanoreceptors. The aim of this study was to describe the existence and
      distribution of LCLC mechanoreceptors in the human elbow joint and to determine
      their role in providing joint stability. Methods: Eight LCLCs were harvested from
      fresh frozen cadaver elbows. Specimens were carefully separated from the lateral
      epicondyle and ulna. The ligament complex was divided into 7 regions of interest
      and stained with modified gold chloride. Microscopic evaluation was performed for
      Golgi, Ruffini, and Pacinian corpuscles. The number, distribution, and density of
      each structure were recorded. Results: Golgi, Ruffini, and Pacinian corpuscles
      were observed in LCLCs, with variable distribution in each region of interest.
      Ruffini corpuscles showed the highest total mechanoreceptor density.
      Mechanoreceptor density was higher at bony attachment sites. Conclusion: The
      existence and role of each mechanoreceptor defined the purpose of each region of
      interest. Mechanoreceptors are beneficial for its proprioceptive feature towards
      a successful elbow ligament reconstruction.

PMID- 30302314
TI  - The non-reconstructive treatment of complete ACL tear with biological enhancement
      in clinical and preclinical studies: A systematic review.
AB  - Introduction: There is still controversy regarding the bio-enhanced non
      reconstructive ACL treatment. Materials and methods: A search for articles in
      databases was performed in February 2017. The objective and subjective
      evaluations of clinical studies and biomechanical and histological data of
      preclinical studies were extracted. Results: Eighteen articles were included for
      analysis. In clinical studies, although subjective scores were significantly
      improved, the rate of re-operation rate was high. In preclinical studies, bio
      enhancing techniques demonstrated promotion of the healing of ACL. Conclusions:
      The efficacy of biological enhancement cannot be validated in clinical studies.
      Preclinical studies showed improved biomechanical and healing potential.

PMID- 30302316
TI  - A cadaveric study on the anatomy of anterior cruciate ligament in Vietnamese
      adults.
AB  - Objectives: To report the anatomical characteristics of the ACL in Vietnamese
      individuals. Subjects and methods: Ten fresh knees were dissected to investigate
      the anatomical characteristics of ACL. The insertion position, length and
      diameter of ACL were measured. Results: The average lengths of AM and PL bundle
      of the ACL were 30.6 mm and 25.6 mm, respectively. The average sizes of the
      femoral and tibial ACL attachment sites were 13.8 * 10.6 mm and 13.4 * 10.2 mm,
      respectively. Conclusion: The anatomical characterisitcs of the ACL in Vietnamese
      individuals were reported.

PMID- 30302318
TI  - Effects of storage time and temperature on greenhouse gas samples in Exetainer
      vials with chlorobutyl septa caps.
AB  - Measurement of greenhouse gas (GHG) flux using static chamber methods typically
      occurs immediately following sample collection. However, situations may arise
      requiring sample storage prior to analysis by gas chromatography. The objective
      of this study was to determine effects of storage time and temperature on carbon
      dioxide (CO2), methane (CH4), and nitrous oxide (N2O) concentrations in vials
      containing "low" and "high" concentrations of certified standards. Samples were
      stored for 3, 7, 14, 28, and 84 days at four storage temperatures: room
      temperature, 25  degrees C, 4  degrees C, and -10  degrees C. Results indicated
      low and high concentration standards were not impacted by sample storage up to 28
      days at any storage temperature. After 84 days, CO2 concentrations were 0.6-14.4%
      lower than expected while CH4 concentrations were up to 22% greater than
      expected. Results from future studies will allow for further refinement of
      scientifically supported guidance regarding appropriate storage temperature and
      time of GHG samples. *Few studies have examined impacts of storage time and
      temperature on GHG samples retained in traditional septa-capped vials.*Effects of
      storage time and temperature on GHG samples were examined.*Based on this study,
      GHG samples can be stored for up to 28 days at temperatures ranging from -10 
      degrees C to 25  degrees C.

PMID- 30302317
TI  - The impact of schizophrenia and intelligence on the relationship between age and
      brain volume.
AB  - Age has been shown to have an impact on both grey (GM) and white matter (WM)
      volume, with a steeper slope of age-related decline in schizophrenia compared to
      healthy controls. In schizophrenia, the relation between age and brain volume is
      further complicated by factors such as lower intelligence, antipsychotic
      medication, and cannabis use, all of which have been shown to have independent
      effects on brain volume. In a study of first-episode, antipsychotic-naive
      schizophrenia patients (N = 54) and healthy controls (N = 56), we examined the
      effects of age on whole brain measures of GM and WM volume, and whether these
      relationships were moderated by schizophrenia and intelligence (IQ). Secondarily,
      we examined lifetime cannabis use as a moderator of the relationship between age
      and brain volume. Schizophrenia patients had lower GM volumes than healthy
      controls but did not differ on WM volume. We found an age effect on GM indicating
      that increasing age was associated with lower GM volumes, which did not differ
      between groups. IQ did not have a direct effect on GM, but showed a trend-level
      interaction with age, suggesting a greater impact of age with lower IQ. There
      were no age effects on WM volume, but a direct effect of IQ, with higher IQ
      showing an association with larger WM volume. Lifetime cannabis use did not alter
      these findings significantly. This study points to effects of schizophrenia on GM
      early in the illness, before antipsychotic treatment is initiated, suggesting
      that WM changes may occur later in the disease process.

PMID- 30302319
TI  - An index for discrimination of mangroves from non-mangroves using LANDSAT 8 OLI
      imagery.
AB  - Over the last few decades several vegetation indices were used to map Mangrove
      forest using satellite images. Difficulty still persists in discrimination of
      mangroves from non-mangrove vegetation, especially in areas where mangrove
      species are mixed with other vegetation types. In the present study we have
      attempted to develop an improved index, which utilizes the information from the
      Normalized Difference Vegetation Index (NDVI) and the Normalized Difference Water
      Index (NDWI) of Bhitarkanika mangrove forest of Odisha, India. These indices are
      negatively correlated (r = -0.988; p < 0.01). Further, the NDWI values were
      subtracted from the NDVI values at the pixel level. As the outputs are negatively
      related, subtraction increases the upper and lower range of the overall output,
      also increasing the distinct values of two classes with near-similar spectral
      signatures. Same algorithm was applied on mangroves of Sundarbans (r = -0.987)
      and Andaman (r = -0.989). A comparison between four established indices [NDVI,
      NDWI, Soil Adjusted Vegetation Index (SAVI), Simple Ratio (SR)] and the newly
      developed index namely Combined Mangrove Recognition Index (CMRI) were performed.
      Accuracy assessment using Kappa statistics, revealing that CMRI produces better
      accuracy (73.43%) compared to other indices, followed by NDVI (56.29%) and SR
      (48.79%).

PMID- 30302320
TI  - Retinal tissue preparation for high-resolution live imaging of photoreceptors
      expressing multiple transgenes.
AB  - Live imaging has become the favorite method in recent years to study the protein
      transport, localization and dynamics in live cells. Protein transport is
      extremely essential for proper function of photoreceptors. Aberration in the
      proper transport of proteins gives rise to the loss of photoreceptor and
      blindness. On the other hand, the ease of generation of transgenic Xenopus laevis
      tadpoles and the advantage of high resolution live confocal imaging provide new
      insight into understanding protein dynamics in photoreceptors. There are several
      steps for quantifying and visualizing fluorescently tagged proteins in
      photoreceptors starting with assembly of plasmids, generation of transgenic
      tadpoles, preparation of retinal tissues, imaging the transgenic photoreceptors
      and finally analyzing the recorded data. The focus of this manuscript is to
      describe how to prepare retinal tissues suited for live cell imaging and provide
      our readers with a tutorial video. We also give a summary of steps leading to a
      successful experiment that might be designed for imaging the ultrastructures of
      photoreceptors, the expression of two or more different fluorescently tagged
      proteins, their localization, distribution, or protein dynamics within
      photoreceptors. *Retinal tissue live imaging demonstrates the ultrastructures of
      photoreceptors.*High resolution live confocal imaging provides new insight into
      understanding the pathophysiology of photoreceptors.

PMID- 30302321
TI  - Adsorptive removal of noxious cadmium from aqueous solutions using poly urea
      formaldehyde: A novel polymer adsorbent.
AB  - Cadmium is a heavy metal toxic that enters water resources through industrial,
      household, agricultural waste and non-sanitary landfill of urban and industrial
      wastes. Pollution of water resources by cadmium increases incidence of diseases
      including Itai-Itai, kidney disorders, cancer, chromosome effects and kidney
      tubular damages in low exposures. The aim of this study is to study the
      efficiency of a new poly urea-formaldehyde adsorbent in the removal cadmium ions
      from aqueous solutions. The effect of different variables such as initial pH,
      contact time, initial concentration of cadmium and test of real wastewater
      samples were evaluated. In addition, laboratory data of cadmium adsorption by
      urea-formaldehyde adsorbent were matched to Langmuir, Freundlich and Temkin
      isotherm models. The results of the study showed that maximum adsorption capacity
      obtained by Langmuir model was 76.3 mg/g at pH = 5.5. Laboratory adsorption data
      matched mostly by Freundlich isotherm model (R2 =0.999) which indicates that
      adsorption of cadmium ions on heterogenic surfaces of poly urea-formaldehyde
      happens by chemical adsorption mechanism. Generally, the results of the study
      showed that new poly urea-formaldehyde adsorbent can be efficiently used to
      remove highly concentrated cadmium ions from aqueous solutions.

PMID- 30302322
TI  - Protocol for assembling micro- and nanoparticles in a viscous liquid above a
      vibrating plate.
AB  - In this protocol, we demonstrate the use of a vibrating plate to drive the
      assembly of micro- and nanoparticles as an approach to high-throughput, large
      scale directed assembly in a viscous liquid. Vibration drives the assembly of
      glass bead microparticles and iron oxide nanoparticles in contact with water over
      an area of 6400 mm2. We use a scaling analysis to show that there is a
      competition between acoustic radiation force and vibration-generated fluid flow
      in a viscous medium, which determines particle transport characteristics. For
      assembly in a viscous liquid, we find close agreement between the observed
      experimental results when compared to a numerical solution of the 2D wave
      equation that describes plate displacement. This model indicates that
      microparticles migrate along displacement gradients towards displacement anti
      nodes where the magnitude of displacement is maximum. We also observe that
      nanoparticles migrate toward displacement nodes where the magnitude of
      displacement is zero. *Cost-effective directed assembly technique without the
      need for microfabrication facilities*Large-scale assembly produces
      heterogeneously ordered structures on a vibrating substrate.

PMID- 30302323
TI  - Various stem cells in acupuncture meridians and points and their putative roles.
AB  - Traditional Chinese and Korean medicine uses various manipulations on acupuncture
      points/acupoints that are located along imaginary lines on the surface of a human
      body, which are called 'meridians'. Acupuncture has been used from the ancient
      time till now to cure various diseases, including for the purpose of regenerative
      medicine. In various studies, meridians are alternatively called as Bong-Han
      ducts, primo vessels, or hyaluronic-acid rich ducts, while acupoints are called
      Bong-Han corpuscles, primo nodes, or hyaluronic-acid rich nodes. Meridians and
      acupuncture points form a system that is now called primo vascular system (PVS),
      which is claimed to contain various kinds of stem cells. The stem cell size is
      between 1-5 microns. The smallest is the primo microcells that have a putative
      role in regeneration. Other stem cells are adult pluripotent and hematopoietic
      stem cells that play a role in extra bone marrow hematopoiesis. The presence of
      PVS has been reproduced by many studies. However, the various stem cells need
      further studies to prove their existence and function, and harvesting PVS to
      isolate the stem cells might harm the health of the donor.

PMID- 30302324
TI  - A review of antioxidant and pharmacological properties of phenolic compounds in
      Acacia confusa.
AB  - In the present review article, the phytochemical, antioxidant and pharmacological
      studies are congregated and summarized concerning the current knowledge of the
      phenolic compounds of a traditional medical plant Acacia confusa in Taiwan. This
      plant is native to Taiwan and South-East Asia. It possesses major pharmacological
      activities, including antioxidant and radical scavenging activity,
      hepatoprotective effect, xanthine oxidase inhibition, semicarbazide-sensitive
      amine oxidase inhibition, angiotensin I converting enzyme inhibition,
      antihyperuricemic effect and anti-inflammatory activity. Phenolic compounds,
      especially flavonoids, flavonol glycoside and phenolic acid derivatives, are the
      main phytochemical compounds isolated from different plant parts of A. confusa.
      Recent interest in this species has focused on pharmacological investigations of
      the phytochemicals which exhibit potent antioxidant activity based on the
      multiple phenolic functionalities. The consequence of this review will further
      extend the potential applications of this plant and offer persuasive support to
      its future use in the fields of clinical medicine and health functional food.

PMID- 30302325
TI  - Herbal beverages: Bioactive compounds and their role in disease risk reduction -
      A review.
AB  - There is a renewed interest in non-nutritive bioactive compounds of foods and
      beverages as 'lifespan nutrients' in the risk reduction of non-communicable
      diseases. Herbal beverages, consumed as part of a balanced diet, may improve the
      antioxidant status and enhance the overall health status. Herbal teas/beverages
      are rich sources of natural bioactive compounds such as carotenoids, phenolic
      acids, flavonoids, coumarins, alkaloids, polyacetylenes, saponins and terpenoids,
      among others. A wealth of available scientific evidence demonstrates that natural
      bioactive compounds render a number of diversified biological effects, such as
      antioxidant, antibacterial, antiviral, antiinflammatory, antiallergic,
      antithrombotic and vasodilatory actions, as well as antimutagenicity,
      anticarcinogenicity and antiaging effects. A number of herbal beverages are
      consumed globally and some beverages have gained more popularity than others
      depending on their geographical origin. However, in the era of globalization,
      ethnic barriers have gradually been removed and such commodities although from
      different areas, are now universally available as international health-pro
      products.

PMID- 30302326
TI  - In vitro studies of the anticancer action of Tectaria cicutaria in human cancer
      cell lines: G0/G1 p53-associated cell cycle arrest-Part I.
AB  - Objective: The rhizome of Tectaria cicutaria has been used in Indian traditional
      medicine for the treatment of various disorders. The objective of present
      investigation is to screen various extracts of the rhizomes of Tectaria cicutaria
      for anti-cancer activity and to investigate the mechanism involved. Materials and
      methods: The rhizomes of Tectaria cicutaria were extracted with different
      solvents. In vitro anti-cancer activity of different rhizome extracts were
      studied in Human cancer Cell Lines using Sulphorodamine B (SRB) colorimetric
      cytotoxicity assay. The effect of ethanolic extract (TCe) on cell growth
      inhibition, modulation in gene expression, and induction of apoptosis using the
      K562 human leukemia cell line were studied. The extract was analyzed by GC-MS to
      identify their major chemical compounds. Results: TCe shows antioxidant potential
      in both DPPH scavenging assay and reducing capacity. Flow cytometric analysis
      showed that 11 MUg/ml of TCe arrested cell cycle progression at the G0/G1 phase.
      In the TCe treated K562 cells, the mRNA and protein expression level of p53 was
      strongly up-regulated in reverse transcription polymerase chain reaction.
      Furthermore, its downstream target p21 level was also increased. The GC-MS study
      has depicted results with the presence of twelve different compounds which will
      require significant further efforts for structure and putative identification.
      Conclusion: The present work has for the first time, tried to elucidate the anti
      leukemic potential of Tectaria cicutaria. TCe was more potent in K562 cells,
      altering the cell cycle progression and inducing apoptosis.

PMID- 30302327
TI  - Rosemary leaves extract: Anti-snake action against Egyptian Cerastes cerastes
      venom.
AB  - The morbidity caused by viper bites is very dangerous and the anti-venom therapy
      couldn't treat the local injures such as hemorrhage, edema, necrosis and
      inflammation of bitten tissues. Searching for safe and effective anti-venom
      compounds from natural sources is very important. This study was designed to
      explore the neutralizing ability of Rosmarinus officinalis L. leaves aqueous
      extract (RMAE) against Egyptian Cerastes cerastes (Cc) viper venom toxicity. The
      RMAE contained a considerable amount of phenolic and flavonoid contents with
      3,300 and 800 mg/100 g dry weight, respectively. The RMAE showed a considerable
      variation of phenolic acids by using HPLC technique. Rosmarinic acid is the major
      component of the RMAE which recorded 400 mg/100 g dry weight and 64% of all the
      identified compounds. In vitro, the RMAE neutralized the enzymatic activities of
      proteases, l-amino acid oxidases, and phospholipases A2 of the Cc venom dose
      dependently. In addition, the RMAE effectively neutralized the gelatinolytic,
      fibrinogenolytic, hemolytic and procoagulant activities of Cc venom. In vivo, the
      RMAE markedly reduced lethality, hemorrhage, edema, muscle and liver toxicities
      induced by Cc venom. In conclusion, the venom neutralizing property of the RMAE
      gives a new prospect for efficient treatment of the lethal viper bites.

PMID- 30302328
TI  - Extraction, isolation and identification of flavonoid from Chenopodium album
      aerial parts.
AB  - Chenopodium album L., (C. album) (family: Chenopodiaceae) is an annual shrub
      widely grown in Asia, Africa, Europe and North America. It is commonly known as
      Bathua (in Hindi), pigweed, fat hen or lamb-quarters. The leaves of C. album are
      applied as a poultice to bug bites, sunstroke, rheumatic joints and as mild
      laxative. The flavonoids contained in C. album aerial parts were extracted,
      identified and characterized. Sequential soxhlet extraction was subjected to
      preliminary phytochemical screening and flavonoid quantification. The results
      showed that maximum yield of the flavonoid (7.335 mg/g) were obtained from
      acetone extract. This acetone extract was subjected to flash chromatography for
      isolation of flavonoid. Characterization of isolated flavonoid was done by UV,
      IR, 1H & 13C NMR and MS. On the basis of chemical and spectral analysis structure
      was elucidated as 2-(3, 4-dihydroxyphenyl)-3, 5, 7-trihydroxy-4H-chromen-4-one, a
      flavonoid.

PMID- 30302329
TI  - Chemical composition, antioxidant potential, macromolecule damage and
      neuroprotective activity of Convolvulus pluricaulis.
AB  - Herbal medicines are known to mitigate radical induced cell damage. Hence
      identification and scientific validation of herbal medicines contribute to better
      use in Ayurvedic/Unani research. In the present study, we investigated
      antioxidant and anti-apoptotic properties of Convolvulus pluricaulis (C.
      pluricaulis). C. pluricaulis exhibited antioxidant potential evident by free
      radical scavenging activities. C. pluricaulis pretreatment inhibited H2O2 induced
      macromolecule damage such as plasmid DNA damage and AAPH induced oxidation of
      bovine serum albumin and lipid peroxidation of rat hepatic tissues. Further to
      identify the neuroprotective properties of C. pluricaulis, SHSY5Y cells were
      treated with H2O2 with or without pretreatment of C. pluricaulis. The C.
      pluricaulis pretreatment at 50 MUg/ml dose exhibited 50% cell survival against
      100 MUM H2O2 challenge for 24 h and it also decreased the lactate dehydrogenase
      leakage. Further C. pluricaulis pretreatment restored and regulated the
      antioxidant and apoptosis markers such as SOD, CAT, p53, and caspase-3 and
      inhibited, reactive oxygen species generation and depolarization of the
      mitochondrial membrane. C. pluricaulis possess a high content of flavonoids and
      polyphenols and GC-MS and FTIR analysis showed a wide variety of compounds which
      may contribute to the observed effects.

PMID- 30302330
TI  - Anti-inflammatory and preventive activity of white mulberry root bark extract in
      an experimental model of pancreatitis.
AB  - Pancreatitis is characterized by highly morbid inflammation in the pancreas.
      Currently, there is no specific drug available for pancreatitis except supportive
      medicines. The present study assessed the pancreato-protective effect of Morus
      alba root bark extract by using alcohol and cerulein-induced model of
      pancreatitis. The study also investigated the phytochemical profile through GC-MS
      and HPLC. Methanolic extract of Morus alba root bark extract (MEMARB) was
      subjected to GC-MS and HPLC studies. Male albino Wistar rats were administered
      ethanol (0%-36%) and cerulein (20 MUg/kg b.wt. i.p.) with or without MEMARB.
      Serum lipase, amylase, caspase-1, lipid peroxidation products, glutathione and
      enzymatic antioxidants were determined. Histological changes in the pancreas were
      assessed. Cudraflavone B in MEMARB was quantified by HPLC. Significant amount of
      Cudraflavone B was detected by quantitative HPLC. Marked increase in the levels
      of serum amylase, lipase, caspase-1, IL-18 and IL-1beta were observed in ethanol
      and cerulein administered rats than in MEMARB co-administered rats. In MEMARB co
      administered rats, the antioxidant status was restored to near normal levels.
      Histological examinations showed that MEMARB significantly reduced the
      inflammatory and fibrotic changes. The results reveal the potent pancreato
      protective effects of Morus alba root bark. The anti-inflammatory effect of Morus
      alba root bark extract might be due to the presence of various phytonutrients
      including Cudraflavone B.

PMID- 30302331
TI  - Preliminary clinical assessment and non- toxicity evaluation of an ayurvedic
      formulation BGR-34 in NIDDM.
AB  - In view of the overall health impact of NIDDM, inventers understand the necessity
      of improving glycemic control in adults with type 2 diabetes. BGR-34 provides an
      effective treatment option for adults with type 2 diabetes who have been
      inadequately controlled on lifestyle with or without other oral hypoglycemic
      agents (OHGAs) such as metformin, sulfonylurea, or a glitazones. BGR-34 is an
      appropriate option to consider for addition to a managed care drug formulary.
      Treatment with BGR-34 produced clinically relevant and statistically significant
      reductions in all three key measures of glucose control studied -FPG, PPBG and
      HbA1c- when compared with placebo. BGR-34, showed the promising result with
      respect to glycemic parameters in NIDDM patient with a significant reduction in
      fasting blood sugar by 34.3%, postprandial blood sugar 35.5% & glycosylated
      haemoglobin by 20.31% as compared to placebo group showing a reduction by 13.2%,
      10.9% & 10.87% respectively. The trial has also been registered to CTRI, India.
      This study has been registered in the clinical trial registry-India.

PMID- 30302332
TI  - Relaxant effects of Azadirachta indica A. Juss var. siamensis Valeton flower
      extract on isolated rat ileum contractions and the mechanisms of action.
AB  - Azadirachta indica A. Juss var. siamensis Valeton or commonly known as Siamese
      neem is one of the most well-known plant in traditional Ayurvedic medicine. The
      aim of the present study was to investigate the relaxant effects of A. indica on
      isolated rat ileum contractions and its potential underlying mechanisms involved.
      The isometric contractions of ileum segments were investigated in organ baths for
      spontaneous activity and response to aqueous extract of Siamese neem flower
      (SNF). The spasmolytic action of the extract was also assessed on contraction
      induced by acetylcholine and high potassium. Our findings indicate that
      cumulative concentrations of SNF aqueous extract induced relaxant effect on
      spontaneous rat ileum contractions. The extract has also suppressed the
      cumulative concentration response curve for acetylcholine and pottasium ions
      induced contraction. The presence and absence of propranol (antagonist of beta
      adrenergic receptor) and l-Name (antagonist of nitric oxide synthase) in SNF
      aqeous extract co-treatment demonstrated no significant different in term of
      contraction activity when compared to SNF extract treatment alone. The treatment
      of SNF extract caused a significant inhibition in tissue contraction stimulated
      by accumulation of calcium ions. Our results showed the relaxant effect of SNF
      aqueous extract on the isolated rat ileum. In short, the SNF aqueous extract
      exhibited an inhibitory effect on the spontaneous ileum contactions particularly
      on the contraction stimulated by acetylcholine and high potassium. The observed
      effect might acted through the modulation of calcium channels. This findings
      provide a pharmacological basis for the traditional use of SNF for the treatment
      of gastrointestinal spasms.

PMID- 30302333
TI  - F eNO-based asthma management results in faster improvement of airway
      hyperresponsiveness.
AB  - Asthma is characterised by inflammation and respiratory symptoms. Current asthma
      treatment is based on severity of asthma symptoms only. Exhaled nitric oxide
      fraction (F eNO) is not recommended by the Global Initiative for Asthma
      guidelines. The aim was to compare the usefulness of a F eNO guided versus
      symptom-based treatment in achieving improved asthma control assessed by airway
      hyperresponsiveness (AHR). 80 asthmatic patients were included in a double
      blinded, parallel, randomised controlled trial with follow-up visits after 8, 24
      and 36 weeks. Treatment was tailored using either a F eNO or Asthma Control
      Questionnaire (ACQ) based algorithm. Inclusion criteria were asthma symptoms and
      a provocative dose causing a 15% fall in forced expiratory volume in 1 s <635 mg
      mannitol. At each visit AHR, F eNO, ACQ and blood tests were performed. No
      differences between the two groups were found at inclusion. AHR from 8 to 24
      weeks was improved in the F eNO group compared to the ACQ group (response dose
      ratio (RDR) geometric mean (95% CI): 0.02 (0.01-0.04) versus 0.05 (0.03-0.07),
      respectively, p=0.015). AHR to mannitol at 36 weeks showed no differences between
      the two groups (mean difference RDR (95% CI): -0.02 (-0.05-0.02), p=0.3). Total
      doses of inhaled steroid and number of exacerbations were similar (p>0.05). When
      using F eNO as a treatment management tool, lowering of airway responsiveness
      occurred earlier than using ACQ. However, airway responsiveness and asthma
      control after 9 months were similar.

PMID- 30302334
TI  - Hypersensitivity pneumonitis in fish processing workers diagnosed by inhalation
      challenge.
AB  - Hypersensitivity pneumonitis may be caused by occupational exposure in the fish
      processing industry http://ow.ly/GbEf30lFnyk.

PMID- 30302335
TI  - Preventing clinically important deterioration with single-inhaler triple therapy
      in COPD.
AB  - Clinically important deterioration (CID) is a novel composite end-point (lung
      function, health status, exacerbations) for assessing disease stability in
      patients with chronic obstructive pulmonary disease (COPD). We prospectively
      analysed CID in the FULFIL study. FULFIL (ClinicalTrials.gov NCT02345161;
      randomised, double-blind, double-dummy, multicentre study) compared 24 weeks of
      once daily, single-inhaler fluticasone furoate/umeclidinium/vilanterol
      (FF/UMEC/VI) 100/62.5/25 ug with twice daily budesonide/formoterol (BUD/FOR)
      400/12 MUg in patients aged >=40 years with symptomatic advanced COPD (Global
      Initiative for Chronic Obstructive Lung Disease group D). A subset of patients
      received study treatment for up to 52 weeks. Time to first CID event was assessed
      over 24 and 52 weeks using two approaches for the health status component: St
      George's Respiratory Questionnaire and COPD assessment test. FF/UMEC/VI
      significantly reduced the risk of a first CID event by 47-52% versus BUD/FOR in
      the 24- and 52-week populations using both CID definitions (p<0.001). The median
      time to first CID event was >=169 days and <=31 days with FF/UMEC/VI and BUD/FOR,
      respectively. Only stable patients with no CID at 24 weeks demonstrated sustained
      clinically important improvements in lung function and health status at 52 weeks
      versus those who had experienced CID. Once daily, single-inhaler FF/UMEC/VI
      significantly reduced the risk of CID versus twice daily BUD/FOR with a five-fold
      longer period without deterioration.

PMID- 30302336
TI  - Treatment of Punctate Inner Choroidopathy with Choroidal Neovascularization Using
      Corticosteroid and Intravitreal Ranibizumab.
AB  - Background: To evaluate the treatment outcomes of patients with punctate inner
      choroidopathy (PIC) and secondary choroidal neovascularization (CNV). Methods:
      This is a retrospective study of 24 eyes in 22 patients suffering from PIC with
      CNV. Patients were treated with intravitreal ranibizumab monotherapy (14 eyes) or
      combined oral corticosteroid and intravitreal ranibizumab therapy (corticosteroid
      ranibizumab group, 10 eyes). Mean follow-up duration was 24.0 months. We
      evaluated best-corrected visual acuity (BCVA), fundus autofluorescence,
      fluorescein angiography, indocyanine green angiography, and optical coherence
      tomography, before and after treatment. The following variables were compared
      between groups: number of intravitreal ranibizumab injections, BCVA, recurrence
      of CNV, and change in PIC lesions. Results: The ranibizumab monotherapy group
      received an average of 3 intravitreal ranibizumab injections; mean logMAR visual
      acuity improvement was 0.34, and 8 eyes developed recurrent CNV during follow-up.
      The corticosteroid-ranibizumab group received an average of 1.9 intravitreal
      ranibizumab injections; mean logMAR visual acuity improvement was 0.61, and there
      was no recurrence of CNV. Combined corticosteroid-ranibizumab therapy also
      resulted in better resolution of PIC lesions and fewer new PIC lesions.
      Conclusion: Both corticosteroid-ranibizumab treatment and ranibizumab monotherapy
      could significantly improve the vision of PIC patients with CNV. Combined
      corticosteroid and intravitreal ranibizumab treatment appeared to reduce CNV
      recurrence and development of new PIC lesions compared with ranibizumab
      monotherapy.

PMID- 30302337
TI  - Global Trends in Application of Stereology as a Quantitative Tool in Biomedical
      Research.
AB  - Stereology is a quantitative and comparative method that utilizes planes, lines,
      and points for the estimation of three-dimensional parameters in morphological
      studies. It primarily focuses on geometrical features of objects such as number,
      density, length, area, and volume. A scientometric study was conducted to analyze
      global research trends in application of stereology in biomedical research.
      Stereology has gained wide application resulting into design-based stereological
      methods. Data for this study were retrieved from the SCOPUS database. At least
      5,732 publications employing stereology as analytical tool were produced in a
      period of 50 years between 1966 and 2016. Half (2,858; 49.87%) of these
      publications were produced in the last 12 years from 2005 to 2016. The relative
      growth rate (RGR) of publications decreased from 1967 (0.69) to 2016 (0.03)
      whereas the doubling time (DT) increased from 1.00 to 20.56 in the same period. A
      great majority (5,332; 93.02%) of the publications retrieved from SCOPUS were
      journal articles in various biomedical fields. The Journal of Microscopy tops the
      list of journals with at least 205 articles. The most productive country was USA
      with at least 1663 (23.10%) publications and Aarhus Universitet tops the list of
      institutions with at least 306 publications. J.R. Nyengaard was the most prolific
      author who contributed at least 125 publications. The highly cited article had a
      total of 2,054 citations with an average of over 82 citations per year. Given the
      growing importance of stereology in biomedical research, it is necessary to
      promote its application among scholars.

PMID- 30302339
TI  - Mummification in Korea and China: Mawangdui, Song, Ming and Joseon Dynasty
      Mummies.
AB  - Over the decades, mummy studies have expanded to reconstruct a multifaceted
      knowledge about the ancient populations' living conditions, pathologies, and
      possible cause of death in different spatiotemporal contexts. Mainly due to
      linguistic barriers, however, the international knowledge of East Asian mummies
      has remained sketchy until recently. We thus analyse and summarize the outcomes
      of the studies so far performed in Korea and China in order to provide mummy
      experts with little-known data on East Asian mummies. In this report,
      similarities and differences in the mummification processes and funerary rituals
      in Korea and China are highlighted. Although the historical periods, the region
      of excavation, and the structures of the graves differ, the cultural aspects, the
      mechanisms of mummification, and biological evidence appear to be essentially
      similar to each other. Independently from the way they are called locally, the
      Korean and Chinese mummies belong to the same group with a shared cultural
      background.

PMID- 30302340
TI  - Endowing iPSC-Derived MSCs with Angiogenic and Keratinogenic Differentiation
      Potential: A Promising Cell Source for Skin Tissue Engineering.
AB  - Induced pluripotent stem cells (iPSC) hold tremendous potential for personalized
      cell-based therapy for skin regeneration. Aiming to establish human iPSCs as a
      potential cell source for skin tissue engineering, we expect to obtain an
      epidermal-like cell line with angiogenic and keratinogenic differentiation
      potential via inducing iPSC-derived mesenchymal stem cells (iPSC-MSCs) with basic
      fibroblast growth factor (bFGF) and/or keratinocyte growth factor (KGF). The
      results show that iPSC-MSCs were successfully induced with a positive FGFR/KGFR
      expression on the cell surface. BFGF/KGF induction could significantly increase
      the expression of vascularization marker CD31 and keratinization marker CK10,
      respectively, while when combined together, although CD31 and CK10 were still
      positively expressed, their expressions were lower than that of the single
      induction group, suggesting that the effects of the two growth factors interfered
      with each other. This cell line with angiogenic and keratinogenic differentiation
      potential provides a promising new source of cells for the construction of well
      vascularized and keratinized tissue engineered skin, furthermore establishing an
      effective strategy for iPSC-based therapy in skin tissue engineering.

PMID- 30302341
TI  - Protocol for Fecal Microbiota Transplantation in Inflammatory Bowel Disease: A
      Systematic Review and Meta-Analysis.
AB  - Background: Fecal microbiota transplantation (FMT) is an emerging treatment
      approach for inflammatory bowel disease (IBD). The donor selection, the
      separation of fecal bacteria, the frequency of FMT, the way of infusion, the long
      term safety, and efficacy are still uncertain. Aim: To further study the efficacy
      and safety and protocol of FMT for IBD. Methods: A systematic review and meta
      analysis were conducted until February, 2018. Clinical remission was established
      as the primary outcome. Results: A total of 596 paediatric and adult IBD patients
      were enrolled, and 459 patients received FMT therapy. 28.8% (132/459) patients
      achieved clinical remission during follow-up. 53% (241/459) patients achieved
      clinical response. The pooled estimated clinical remission for ulcerative colitis
      (UC) was 21% (95% CI: 8%-37%) and 30% (95% CI: 11%-52%) for Crohn's disease (CD),
      both with a risk of heterogeneity; 10% (95% CI: 0%-43%) for paediatric UC; 26%
      (95% CI: 10%-48%) for adult UC; 45% for paediatric CD (95% CI: 24%-66%); 22% (95%
      CI: 3%-52%) for adult CD. Meta-analysis of cohort studies showed that moderate
      severe IBD patients could achieve more significant remission from FMT than mild
      moderate patients (P=0.037). Delivery route has no impact on the efficacy of FMT
      in UC and CD. Based on current available evidence, a trend was observed towards
      higher clinical remission rate of frozen stool FMT than that of fresh stool for
      UC, while there was no significant difference between fresh and frozen FMT for
      CD. The optimal donor stool for FMT is still uncertain. Meta-analysis of RCTs
      showed that FMT treatment achieved significantly higher clinical remission rate
      than placebo for UC (28% versus 9%, P=0.0003). Conclusion: FMT is an effective
      and safe therapy for both paediatric and adult IBD; fresh or frozen donor stool,
      delivery route, and antibiotic pretreatment or not have no impact on the efficacy
      of FMT in IBD. FMT might be a potential rescue therapy and even an initial
      standardized therapy for IBD. However, few data exist on long-term safety and
      efficacy and further validation is needed.

PMID- 30302338
TI  - Social Cognition through the Lens of Cognitive and Clinical Neuroscience.
AB  - Social cognition refers to a set of processes, ranging from perception to
      decision-making, underlying the ability to decode others' intentions and
      behaviors to plan actions fitting with social and moral, besides individual and
      economic considerations. Its centrality in everyday life reflects the neural
      complexity of social processing and the ubiquity of social cognitive deficits in
      different pathological conditions. Social cognitive processes can be clustered in
      three domains associated with (a) perceptual processing of social information
      such as faces and emotional expressions (social perception), (b) grasping others'
      cognitive or affective states (social understanding), and (c) planning behaviors
      taking into consideration others', in addition to one's own, goals (social
      decision-making). We review these domains from the lens of cognitive
      neuroscience, i.e., in terms of the brain areas mediating the role of such
      processes in the ability to make sense of others' behavior and plan socially
      appropriate actions. The increasing evidence on the "social brain" obtained from
      healthy young individuals nowadays constitutes the baseline for detecting changes
      in social cognitive skills associated with physiological aging or pathological
      conditions. In the latter case, impairments in one or more of the abovementioned
      domains represent a prominent concern, or even a core facet, of neurological
      (e.g., acquired brain injury or neurodegenerative diseases), psychiatric (e.g.,
      schizophrenia), and developmental (e.g., autism) disorders. To pave the way for
      the other papers of this issue, addressing the social cognitive deficits
      associated with severe acquired brain injury, we will briefly discuss the
      available evidence on the status of social cognition in normal aging and its
      breakdown in neurodegenerative disorders. Although the assessment and treatment
      of such impairments is a relatively novel sector in neurorehabilitation, the
      evidence summarized here strongly suggests that the development of remediation
      procedures for social cognitive skills will represent a future field of
      translational research in clinical neuroscience.

PMID- 30302343
TI  - Diabetes and Associated Cardiovascular Complications in American Indians/Alaskan
      Natives: A Review of Risks and Prevention Strategies.
AB  - : Diabetes mellitus (DM) is the seventh leading cause of death in the United
      States and the leading cause of death in the U.S. American Indian/Alaskan Natives
      (AI/ANs), who comprise only 2% of the total population. The AI/AN population has
      a high prevalence of DM in adults aged 20 years or older and is developing DM at
      a younger age than the general U.S. POPULATION: DM is a major risk factor for
      cardiovascular disease (CVD), and mortality from CVD is higher in AI/ANs than the
      general population, as is the prevalence of stroke and 1-year poststroke
      mortality for both genders when compared to non-Hispanic whites. A genome-wide
      scan found a number of chromosome linkages in the AI/AN population that suggest
      that genetic factors may contribute to their high risk of DM and CVD.
      Importantly, studies also suggest that in addition to race/ethnicity, cultural
      norms and historic conditions play important roles in the prevalence of DM and
      CVD in this population. Therefore, multiple factors should be taken into
      consideration when establishing prevention programs to decrease the prevalence of
      obesity, diabetes, and CVD incidence among adults and children in the AI/AN
      population. Prevention programs should focus on behavioral risk factors and
      lifestyle changes like encouraging smoking cessation, healthy diet, and increased
      physical activity while taking into consideration cultural, economic, and
      geographic factors.

PMID- 30302342
TI  - Frailty and Exercise Training: How to Provide Best Care after Cardiac Surgery or
      Intervention for Elder Patients with Valvular Heart Disease.
AB  - The aim of this literature review was to evaluate existing evidence on exercise
      based cardiac rehabilitation (CR) as a treatment option for elderly frail
      patients with valvular heart disease (VHD). Pubmed database was searched for
      articles between 1980 and January 2018. From 2623 articles screened, 61 on
      frailty and VHD and 12 on exercise-based training for patients with VHD were
      included in the analysis. We studied and described frailty assessment in this
      patient population. Studies reporting results of exercise training in patients
      after surgical/interventional VHD treatment were analyzed regarding contents and
      outcomes. The tools for frailty assessment included fried phenotype frailty index
      and its modifications, multidimensional geriatric assessment, clinical frailty
      scale, 5-meter walking test, serum albumin levels, and Katz index of activities
      of daily living. Frailty assessment in CR settings should be based on functional,
      objective tests and should have similar components as tools for risk assessment
      (mobility, muscle mass and strength, independence in daily living, cognitive
      functions, nutrition, and anxiety and depression evaluation). Participating in
      comprehensive exercise-based CR could improve short- and long-term outcomes
      (better quality of life, physical and functional capacity) in frail VHD patients.
      Such CR program should be led by cardiologist, and its content should include (1)
      exercise training (endurance and strength training to improve muscle mass,
      strength, balance, and coordination), (2) nutrition counseling, (3) occupational
      therapy (to improve independency and cognitive function), (4) psychological
      counseling to ensure psychosocial health, and (5) social worker counseling (to
      improve independency). Comprehensive CR could help to prevent, restore, and
      reduce the severity of frailty as well as to improve outcomes for frail VHD
      patients after surgery or intervention.

PMID- 30302345
TI  - Carbamazepine-Mediated Adverse Drug Reactions: CBZ-10,11-epoxide but Not
      Carbamazepine Induces the Alteration of Peptides Presented by HLA-B*15:02.
AB  - Among patients treated with the anticonvulsive and psychotropic drug
      carbamazepine (CBZ), approximately 10% develop severe and life-threatening
      adverse drug reactions. These immunological conditions are resolved upon
      withdrawal of the medicament, suggesting that the drug does not manifest in the
      body in long term. The HLA allele B*15:02 has been described to be a genomic
      biomarker for CBZ-mediated immune reactions. It is not well understood if the
      immune reactions are triggered by the original drug or by its metabolite
      carbamazepine-10,11-epoxide (EPX) and how the interaction between the drug and
      the distinct HLA molecule occurs. Genetically engineered human B-lymphoblastoid
      cells expressing soluble HLA-B*15:02 molecules were treated with the drug or its
      metabolite. Functional pHLA complexes were purified; peptides were eluted and
      sequenced. Applying mass spectrometric analysis, CBZ and EPX were monitored by
      analyzing the heavy chain and peptide fractions separately for the presence of
      the drug. This method enabled the detection of the drug in a biological situation
      post-pHLA assembly. Both drugs were bound to the HLA-B*15:02 heavy chain;
      however, solely EPX altered the peptide-binding motif of B*15:02-restricted
      peptides. This observation could be explained through structural insight; EPX
      binds to the peptide-binding region and alters the biochemical features of the F
      pocket and thus the peptide motif. Understanding the nature of immunogenic
      interactions between CBZ and EPX with the HLA immune complex will guide towards
      effective and safe medications.

PMID- 30302344
TI  - Cancer Immunotherapy: Priming the Host Immune Response with Live Attenuated
      Salmonella enterica.
AB  - In recent years, cancer immunotherapy has undergone great advances because of our
      understanding of the immune response and the mechanisms through which tumor cells
      evade it. A century after the first immunotherapy attempt based on bacterial
      products described by William Coley, the use of live attenuated bacterial vectors
      has become a promising alternative in the fight against cancer. This review
      describes the role of live attenuated Salmonella enterica as an oncolytic and
      immunotherapeutic agent, due to its high affinity for tumor tissue and its
      ability to activate innate and adaptive antitumor immune response. Furthermore,
      its potential use as delivery system of tumor antigens and immunomodulatory
      molecules that induce tumor regression is also reviewed.

PMID- 30302346
TI  - An Esophagogram or Tracheobronchogram? A Review of Barium Sulfate Aspiration.
AB  - The barium swallow is an important radiological investigation used for the
      diagnosis of upper gastrointestinal anatomical disorders like esophageal cancer,
      diverticulum, achalasia, foreign body, among others. Generally, it is believed to
      be a safe technique with rare complications, but few cases of barium sulfate
      aspiration have been reported in the literature with multiple complications. We
      are reporting a case of an elderly male who underwent esophagogram for the workup
      of chronic dysphagia, aspirated barium sulfate, and went into respiratory failure
      and circulatory shock several hours later. Moreover, we also did a systematic
      literature search and reviewed all available articles on aspiration of barium
      sulfate and its potential complications. We focused on predisposing factors for
      aspiration, clinical presentation, complications after aspiration, and prognosis
      with the aim to better understand and manage this condition.

PMID- 30302347
TI  - Effect of Posterior Glenoid Labral Tears at the NFL Combine on Future NFL
      Performance.
AB  - Background: Posterior labral injuries have been recognized as a particularly
      significant clinical problem in collision and contact athletes. Purpose: To
      evaluate the effect that posterior labral tears have on early National Football
      League (NFL) performance based on position, associated injuries, and operative
      versus nonoperative management. Study Design: Cohort study; Level of evidence, 3.
      Methods: A retrospective review of all participants in the NFL Combine from 2009
      to 2015 was performed using medical and imaging reports documented at the
      combine. Magnetic resonance imaging scans were analyzed for tear location,
      associated injuries, and evidence of previous surgical interventions. Each
      player's NFL draft position, as well as number of games played, number of games
      started, and snap percentage in his first 2 NFL seasons were collected for
      performance analysis and were compared with a control group of uninjured
      counterparts. Results: Players with posterior labral tears were selected
      significantly later in the draft than those in the control group (draft position,
      171.6 vs 156.1, respectively; P = .017). Although no single individual position
      was significantly affected by posterior labral tears, linemen (both offensive and
      defensive) with posterior labral tears were drafted significantly later than
      those without tears (draft position, 164.0 vs 137.7, respectively; P = .018) and
      had a significantly lower percentage of snaps in their first NFL season (23.8% vs
      27.7%, respectively; P = .014). Players who underwent surgical management before
      the combine had a significantly higher percentage of snaps in their second NFL
      season than those who were managed conservatively (31.4% vs 22.3%, respectively;
      P = .022). None of the concomitant injuries recorded (superior labral anterior
      posterior tears, glenoid bone loss, reverse Hill-Sachs lesions, rotator cuff
      tears, reverse humeral avulsions of the glenohumeral ligament, and posterior
      labral tears combined with anterior tears) significantly affected the draft
      position, number of games played, number of games started, or snap percentage for
      the cohort as a whole or any specific position. Conclusion: Posterior labral
      tears did negatively and significantly affect early NFL outcomes for collegiate
      football players across several different metrics, especially among linemen.
      While operative management did not produce significantly superior performance in
      most outcome measures, it may allow for better longevity of the shoulder and
      warrants further investigation. Concomitant shoulder injuries did not
      significantly affect early NFL outcomes in this cohort.

PMID- 30302348
TI  - The Rapidly Assessed Predictor of Intraoperative Damage (RAPID) Score: An In
      Clinic Predictive Model for High-Grade Acetabular Chondrolabral Disruption.
AB  - Background: The preoperative assessment of cartilage lesions is critical to
      surgical planning and decision making. The accurate radiographic determination of
      acetabular cartilage damage has remained elusive for modern imaging modalities,
      including magnetic resonance imaging (MRI) and magnetic resonance arthrography
      (MRA). While risk factors have been individually described, no multivariable
      system exists for predicting high-grade cartilage damage. Purpose: To determine
      the preoperative predictors of grade 3 to 4 acetabular labrum articular
      disruption (ALAD) lesions. Study Design: Case-control study; Level of evidence,
      3. Cohort study (diagnosis); Level of evidence, 1. Methods: Retrievable
      radiographs were reviewed from primary hip arthroscopic procedures performed at 2
      high-volume institutions between December 2007 and April 2017. The predictive
      value of demographic and radiographic factors for the intraoperative
      documentation of ALAD grade 3 to 4 damage was analyzed and entered into a
      multivariable model, and a statistically guided scoring system for the damage
      risk was created using the Akaike information criterion. The scoring system was
      then prospectively validated on 167 patients who underwent primary hip
      arthroscopy between April 2017 and February 2018. Results: A total of 652 primary
      hip arthroscopic procedures in 614 patients (390 female, 224 male; mean age, 33.2
      +/- 12.5 years; mean body mass index, 26.9 +/- 5.5 kg/m2) from 2007 to 2017 were
      analyzed. Male sex (odds ratio [OR], 3.11; P < .01), age >=35 years (OR, 1.96; P
      < .01), cam morphology (alpha angle >55 degrees ) (OR, 2.96; P < .01), and Tonnis
      grade 1 to 2 (grade 1: OR, 4.14; P < .01, and grade 2: OR, 9.29; P < .01) were
      univariate risk factors for intraoperatively documented high-grade damage. A
      multivariable scoring system, the Rapidly Assessed Predictor of Intraoperative
      Damage (RAPID) score (0-5 points), was generated based on sex, Tonnis grade, and
      cam morphology. Patients with increasing RAPID scores had an increasing risk of
      damage, with a 10.5% risk for those with 0 points and an 88.0% risk for those
      with 5 points (P < .01). The area under the curve was 0.75 for the study group
      and 0.76 for the validation group (P = .94). Conclusion: While preoperative MRI
      has diagnostic value for hip arthroscopic surgery, the RAPID score provides added
      benefit as a readily employable, in-clinic system for predicting high-grade
      cartilage damage. The discriminatory value of the RAPID score compares favorably
      with previous MRI and MRA studies. This information will help the clinician and
      patient plan for high-grade damage and identify potential targets for cartilage
      treatment.

PMID- 30302349
TI  - Diagnostic Accuracy of the Scapular Retraction Test in Assessing the Status of
      the Rotator Cuff.
AB  - Background: Currently, clinical physical examination maneuvers alone provide
      variable reliability in diagnosing full-thickness rotator cuff tears (RCTs).
      Purpose: To assess the diagnostic accuracy of the scapular retraction test (SRT)
      to predict full-thickness RCTs. Study Design: Cohort study (diagnosis); Level of
      evidence, 2. Methods: A total of 331 patients were prospectively evaluated in
      this cohort study. SRT was performed to assess the status of the rotator cuff. A
      positive SRT indicates an intact rotator cuff, and a negative SRT indicates a
      full-thickness RCT. Magnetic resonance imaging (MRI) was used as the gold
      standard. The examiner was blinded to the results until completing the physical
      examination. Statistical analysis was performed to assess the sensitivity,
      specificity, accuracy, positive and negative predictive values, and positive and
      negative likelihood ratios of the SRT. Results: The prevalence of full-thickness
      RCTs diagnosed on MRI was 54.4% (180 of 331). Among the 180 patients with an MRI
      confirmed full-thickness RCT, the SRT was negative for 147. Of 150 patients with
      an intact rotator cuff by MRI, 122 had a positive SRT. In diagnosing full
      thickness RCTs, the SRT had a sensitivity of 81.7% (95% CI, 77.2%-85.4%),
      specificity of 80.8% (95% CI, 75.5%-85.3%), and accuracy 81.3%. The positive
      predictive value was 83.5% (95% CI, 78.9%-87.4%); the negative predictive value,
      78.7% (95% CI, 73.5%-83.1%); the positive likelihood ratio, 4.3 (95% CI, 3.1
      5.8); the negative likelihood ratio, 0.23 (95% CI, 0.17-0.30); and the diagnostic
      odds ratio, 18.7 (95% CI, 10.4-34.0). Conclusion: The results of this diagnostic
      study indicate that the SRT can accurately be used to clinically assess the
      status of the rotator cuff. This physical examination maneuver was found to be
      accurate, sensitive, and specific in diagnosing full-thickness RCTs.
      Additionally, our results indicate that it is equally as accurate to predict an
      intact rotator cuff tendon. Providing an accurate, reliable, and reproducible
      physical examination test will allow clinicians to diagnosis the integrity of the
      rotator cuff and will help guide treatment recommendations.

PMID- 30302350
TI  - Cost of Public Health Response and Outbreak Control With a Third Dose of Measles
      Mumps-Rubella Vaccine During a University Mumps Outbreak-Iowa, 2015-2016.
AB  - Background: The United States is experiencing mumps outbreaks in settings with
      high 2-dose measles-mumps-rubella (MMR) vaccine coverage, mainly universities.
      The economic impact of mumps outbreaks on public health systems is largely
      unknown. During a 2015-2016 mumps outbreak at the University of Iowa, we
      estimated the cost of public health response that included a third dose of MMR
      vaccine. Methods: Data on activities performed, personnel hours spent, MMR
      vaccine doses administered, miles traveled, hourly earnings, and unitary costs
      were collected using a customized data tool. These data were then used to
      calculate associated costs. Results: Approximately 6300 hours of personnel time
      were required from state and local public health institutions and the university,
      including for vaccination and laboratory work. Among activities demanding time
      were case/contact investigation (36%), response planning/coordination (20%), and
      specimen testing and report preparation (13% each). A total of 4736 MMR doses
      were administered and 1920 miles traveled. The total cost was >$649 000, roughly
      equally distributed between standard outbreak control activities and third-dose
      MMR vaccination (55% and 45%, respectively). Conclusions: Public health response
      to the mumps outbreak at the University of Iowa required important amounts of
      personnel time and other resources. Associated costs were sizable enough to
      affect other public health activities.

PMID- 30302351
TI  - Epidemiology of Carbapenem-Resistant Enterobacteriaceae at a Long-term Acute Care
      Hospital.
AB  - Background: Residents of long-term acute care hospitals (LTACHs) are considered
      important reservoirs of multidrug-resistant organisms, including Carbapenem
      resistant Enterobacteriaceae (CRE). We conducted this study to define the
      characteristics of CRE-infected/colonized patients admitted to an LTACH and the
      molecular characteristics of the CRE isolates. Methods: This retrospective study
      was conducted to collect information on demographic and comorbid conditions in
      CRE-colonized/infected patients admitted to a 77-bed LTACH in Detroit between
      January 2011 and July 2012. Data pertaining to hospital-related exposures were
      collected for 30 days before positive CRE culture. Polymerase chain reaction
      (PCR) gene amplification, repetitive sequence-based PCR, and multilocus sequence
      typing (MLST) were performed on 8 of the CRE isolates. Results: The study cohort
      included 30 patients with CRE-positive cultures, 24 (80%) with infections, and 6
      (20%) with colonization. The mean age of cohort was 69 +/-12.41 years; 19 (63%)
      patients were ventilator-dependent, and 20 (67%) were treated with at least 1
      antibiotic. Twenty-three (77%) patients had CRE detected following LTACH
      admission, and the median days from admission to CRE detection in these patients
      (interquartile range) was 25 (11-43). Seven more patients were already positive
      for CRE at the time of LTACH admission. Molecular genotyping and MLST of 8 CRE
      isolates demonstrated that all isolates belonged to the same strain type (ST258)
      and contained the bla KPC-3 sequence. Conclusions: The majority of patients with
      CRE presented several days to weeks after LTACH admission, indicating possible
      organism acquisition in the LTACH itself. The genetic similarity of the CRE
      isolates tested could further indicate the occurrence of horizontal transmission
      in the LTACH or simply be representative of the regionally dominant strain.

PMID- 30302352
TI  - Real-World Experience With Higher-Than-Recommended Doses of Lamivudine in
      Patients With Varying Degrees of Renal Impairment.
AB  - Background: Although nucleoside reverse transcriptase inhibitors have been
      associated with lactic acidosis, lamivudine (3TC) has not been reported to have
      an increased risk with elevated concentrations. Therefore, some recommend that
      the lowest tablet strength of 3TC be considered in patients with kidney disease
      to avoid the inconvenience of liquid formations. Our institution avoids dose
      adjusting 3TC until creatinine clearance (CrCl) <30 mL/min and uses 100-150-mg
      tablets daily in hemodialysis. The aim of this study was to describe the use of
      higher-than-recommended doses of 3TC in a real-world setting. Methods: Blood
      samples were collected before and 0.5-1.5 hours after 3TC administration in HIV+
      adults. Predose (Cmin) and postdose (Cmax) samples were measured by high
      performance liquid chromatography. Physiologically based pharmacokinetic modeling
      was utilized to simulate areas under the curve (AUCs) and profiles by CrCl.
      Lactic acid levels and patient-reported adverse events were obtained to monitor
      for safety, and viral suppression was assessed for efficacy. Results: Thirty-four
      patients with varying degrees of renal function were enrolled. Observed 3TC Cmax
      values were comparable among CrCl cohorts. Simulated 3TC AUC values in patients
      with CrCl 30-49, 15-29, and 0-15 mL/min were consistent with historical data, and
      fold-errors were between 0.5 and 2.0. All lactic acid levels were within normal
      limits, and no adverse effects were reported. Conclusions: This study is the
      first to describe the use of higher-than-recommended doses of 3TC in a real-world
      setting. 3TC was well tolerated across all levels of renal function. These
      results can guide providers in their selection of higher 3TC dosing in select
      patients with renal dysfunction to maximize adherence.

PMID- 30302353
TI  - Impact of Case-Specific Education and Face-to-Face Feedback to Prescribers and
      Nurses in the Management of Hospitalized Patients With a Positive Clostridium
      difficile Test.
AB  - Background: Approaches to changing providers' behavior around Clostridium
      difficile (CD) management are needed. We hypothesized that case-specific teaching
      points and face-to-face discussions with prescribers and nurses would improve
      management of patients with a positive CD test. Methods: Charts of patients age
      >=18 years with positive CD tests hospitalized July 2016 to May 2017 were
      prospectively reviewed to assess CD practices and generate management
      recommendations. The study had 4 periods: baseline (pre-intervention),
      intervention #1, observation, and intervention #2. Both interventions consisted
      of an in-person, real-time, case-based discussion and education by a CD Action
      Team (CDAT). Assessment occurred within 24 hours of a positive CD test for all
      periods; during the intervention periods, management was also assessed within 48
      hours after CDAT-delivered recommendations. Outcomes included proportion of
      patients receiving optimized treatment and incidence rate ratios of practice
      changes (both CDAT-prompted and CDAT-independent). Results: Overall, the CDAT
      made recommendations to 84 of 96 CD cases during intervention periods, and
      providers accepted 43% of CDAT recommendations. The implementation of the CDAT
      led to significant improvement in bowel movement (BM) documentation, use of
      proton pump inhibitors, and antibiotic selection for non-CD infections. Selection
      of CD-specific therapy improved only in the first intervention period. Laxative
      use and treatment of CD colonization cases remained unchanged. Only BM
      documentation, a nurse-driven task, was sustained independent of CDAT prompting.
      Conclusions: A behavioral approach to changing the management of positive CD
      tests led to self-sustained practice changes among nurses but not physicians.
      Better understanding of prescribers' decision-making is needed to devise enduring
      interventions.

PMID- 30302354
TI  - Entities of Chronic and Granulomatous Invasive Fungal Rhinosinusitis: Separate or
      Not?
AB  - Background: Chronic and granulomatous invasive fungal rhinosinusitis are
      important causes of blindness and craniocerebral complications. However, the
      classification of these 2 diseases remains controversial. Methods: We
      retrospectively analyzed patients with chronic and granulomatous invasive fungal
      rhinosinusitus in a Chinese tertiary hospital from 2009 to 2017, with a focus on
      classification and comparisons. Results: Among 55 patients enrolled in our study,
      11 (11/55, 20%) had granulomatous invasive fungal rhinosinusitis (GIFRS) and 44
      (44/55, 80%) had chronic invasive fungal rhinosinusitis (CIFRS). Aspergillus
      fumigatus and Dematiaceous hyphomycetes were identified in 2 patients with GIFRS.
      Compared with granulomatous type, CIFRS was more frequently encountered in
      immunocompromised patients (P = .022), and the time from onset to diagnosis was
      much shorter (P = .001). Proptosis and orbital apex syndrome showed no
      significant difference between granulomatous and CIFRS in our study. The
      treatment options and prognosis of both diseases also showed no significant
      difference. Conclusions: Despite the consensus on histopathology, the
      classification of the chronic and granulomatous types may need further evaluation
      in clinical considerations.

PMID- 30302355
TI  - Absolute Lymphocyte Count Thresholds: A Simple, Readily Available Tool to Predict
      the Risk of Cytomegalovirus Infection After Transplantation.
AB  - This study of 64 solid organ and hematopoietic stem cell transplant recipients
      found that peripheral blood absolute lymphocyte count of <610 and <830/uL,
      respectively, correlated with cytomegalovirus infection. In an era when
      sophisticated measures of CMV-specific T cells are emerging, we emphasize the
      utility of the inexpensive and readily-available absolute lymphocyte count.

PMID- 30302356
TI  - Parenting Desires Among Individuals Living With Human Immunodeficiency Virus in
      the United States.
AB  - Background: In 1988, 1 of 3 women (W) and heterosexual men living with human
      immunodeficiency virus (HIV) reported wanting children, but little is known about
      parenting desires of men who have sex with men (MSM) living with HIV. We examined
      parenting desires among persons initiating antiretroviral therapy (ART). Methods:
      Of 1809 participants in the AIDS Clinical Trials Group (ACTG) Study 5257, 1425 W
      aged <=45 years or men completed questionnaires about parenting desires at
      baseline and 96 weeks after initiating ART. Self-reported desires for children in
      the future (yes/unsure vs no) and associations between baseline sociodemographics
      and parenting desires at 96 weeks were examined using multivariable logistic
      regression, overall and within subgroups. Results: The 1425 participants were as
      follows: 36% white, 39% black, 22% Hispanic; median age 36 (interquartile range,
      28-44); 70% MSM, 13% men reported sex only with W (MSW), 17% W. At baseline, 42%
      may want children in the future (42% MSM, 37% MSW, 43% W); at 96 weeks, 41% may
      want children (41% MSM, 37% MSW, 43% W). At follow-up, approximately 10% of
      responses changed in each direction. In multivariable analyses, education greater
      than high school, <30 years, and having no children were significantly associated
      with future parenting desires among all subgroups. Among MSM, being black was
      associated with desiring children. Conclusions: Approximately 40% of MSM, W, and
      MSW with HIV may want children, both at baseline and 96 weeks after ART
      initiation. These results highlight the need to regularly assess parenting goals,
      provide access to comprehensive reproductive services, and address prevention of
      vertical and heterosexual HIV transmission.

PMID- 30302358
TI  - Data on ethyl glucuronide and cocaethylene concentrations in the hair of cocaine
      users.
AB  - We present data on ethyl glucuronide and cocaethylene concentrations from the
      hair of cocaine users. Head hair from 64 subjects, previously tested for cocaine,
      cocaethylene, benzoylecogonine and anhydroecgonine methyl ester (AEME), were
      subsequently analysed for Ethyl Glucuronide (EtG). Samples were prepared by solid
      phase extraction and analysed using gas chromatrography coupled to tandem mass
      spectrometry. The dataset is made available to allow analysis of possible
      correlation between cocaethylene and ethyl glucuronide or between other
      metabolites presented in the data.

PMID- 30302357
TI  - Identification of putative flowering genes and transcription factors from flower
      de novo transcriptome dataset of tuberose (Polianthes tuberosa L.).
AB  - Polianthes tuberosa is commercially popular because of their economic importance
      in floriculture for cut and loose flowers and in perfume industry because of the
      unique fragrance. Despite its commercial importance, no ready-to-use transcript
      sequence information is available in the public database. We have sequenced the
      RNA obtained from tuberose flowers using the Illumina HiSeq. 2000 platform and
      have carried out a de novo analysis of the transcriptome data. The de novo
      assembly generated 11,100 transcripts. These transcripts represent a total of
      7876 unigenes that were considered for downstream analysis. These 7876 unigenes,
      which was further annotated using blast2go and KEGG pathways, were also assigned.
      Tuberose transcripts were also assigned to metabolic pathways using the Kyoto
      Encyclopedia of Genes and Genomes database to determine their biochemical
      functions. 4591 of the tuberose transcripts matched to genes in KEGG pathways and
      66 transcripts were mapped to the Flavonoid biosynthesis pathway. 21 flowering
      genes have been identified in this tuberose transcriptome. Transcription factor
      analysis helped in the identification of a large number of transcripts similar to
      key genes in the flowering regulation network of Arabidopsis thaliana. Among the
      transcription factors identified "NAC" which is associated with plant stress
      response represented the most abundant category followed by APETALA2
      (AP2)/ethylene-responsive element binding proteins (EREBPs) which plays various
      role in floral organ identity and respond to different biotic and abiotic stress.

PMID- 30302359
TI  - EEG data and introspective reports from the Libet's experiment replication.
AB  - This article provides data from a contemporary replication of Libet's experiment.
      For the methodology, results and discussion of the replication, see the article
      "Libet's Experiment: A Complex Replication" (Dominik et al., 2018). Three types
      of data are presented in this article: (1) introspective reports (M, W and S),
      (2) EMG onset times relative to a mouse click or to the target time in tasks with
      a movement at pre-set time and (3) relevant averaged EEG data.

PMID- 30302360
TI  - Proximal nail fold swelling, pain, and granulation tissue.

PMID- 30302361
TI  - Vulvovaginal pyoderma gangrenosum in association with rituximab.

PMID- 30302362
TI  - The use of a suture retention device with punctureless technique for rapid tissue
      expansion in facial and lower extremity wounds.

PMID- 30302363
TI  - Microsurgical lymphaticovenular anastomosis for refractory chylous ascites
      following para-aortic lymph nodes dissection in a patient with tubal cancer.
AB  - *Postoperative chylous ascites is an important clinical issue in surgery for
      gynecological malignancy.*Our patient with refractory chylous ascites after
      surgery for tubal cancer.*She received great benefit from the microsurgical
      lymphaticovenular anastomosis.*The microsurgical lymphaticovenular anastomosis is
      the treatment of choice.*The entire procedure was performed under local
      anesthesia.

PMID- 30302364
TI  - High-risk gestational choriocarcinoma with an unusual presentation and the
      treatment course of refractory or quiescent/minimally invasive disease.
AB  - *A patient with high-risk choriocarcinoma who had refractory or
      quiescent/minimally invasive disease.*She was treated with seven lines of
      chemotherapy and salvage surgeries.*The patient had persistently low hCG levels
      without evidence of disease for 4 years.*Then radiological evidence of pulmonary
      metastasis was finally achieved, and the patient was salvaged by surgery.*It is
      crucial to identify the site of active disease to facilitate surgical resection
      and cure.

PMID- 30302365
TI  - Seroprevlance of Coxiella burnetii among abattoir and slaughterhouse workers: A
      meta-analysis.
AB  - Q fever caused by the gram negative bacteria, Coxiella burnetii, is an
      occupational hazard for those who live and work in rural settings and those who
      are in contact with animals, especially abattoir and slaughterhouse workers.
      Australia is the only country to register a vaccine to prevent Q fever (Q-vax(r),
      Seqirus, Australia) that is used in high risk populations. Seroprevalence studies
      conducted to determine the burden of Q fever (C. burnetii infection) in different
      settings have demonstrated high levels of heterogeneity with estimates of the
      percent positive ranging from 30% to 70%. There is a need for a more systematic
      evaluation of the findings of these studies in order to provide summary estimates
      of the seroprevalence in different settings. We searched for published articles
      using PubMed, MEDLINE-EMBASE, and Scopus databases using search terms obtained
      from an initial review of published reports of recent Q fever outbreaks. Data on
      the seroprevalence of C. burnetii infection (Q fever) was extracted from the
      selected studies and a random effects meta-analysis was performed with
      stratification by outbreak status, year, country and serological techniques used.
      Results were visualised with a forest plot with 95% CI and measures of
      heterogeneity (I 2) for the random effects model. A total of 19 articles that met
      the search criteria were included. The reported seroprevalence rate ranged from
      4.7% to 91.7% among abattoir and slaughterhouse workers. No inter-group
      heterogeneity was observed (p = 0.956), supporting the pooling of all studies
      into one pooled measure. The pooled estimate of seropositivity for C. burnetii
      infection in people working in abattoirs and slaughterhouses was 26% (95% CI: 18
      35%) regardless of the evidence of an "outbreak", the time of year or country.
      Seropositivity for C burnetii was independent of a person's age and years of
      occupational experience. Within abattoirs and slaughterhouses, slaughtering of
      cattle, sheep and goats are the most important risk factors associated with
      seropositivity and for those who showed over symptoms upon infection. We
      recommend that vaccination programmes are directed towards people employed in the
      meat processing industry to mitigate the significant health and economic impacts
      of Q fever.

PMID- 30302366
TI  - Canadian report card on health equity across the life-course: Analysis of time
      trends and cross-national comparisons with the United Kingdom.
AB  - Addressing social determinants of health (SDoH) has been acknowledged as an
      essential objective for the promotion of both population health and health
      equity. Extant literature has identified seven potential areas of investment to
      address SDoH: investments in sexual and reproductive health and family planning,
      early learning and child care, education, universal health care, as well as
      investments to reduce child poverty, ensure sustainable economic development, and
      control health hazards. The aim of this paper is to produce a 'report card' on
      Canada's success in reducing socioeconomic and health inequities pertaining to
      these seven policy domains, and to assess how Canadian trends compare to those in
      the United Kingdom (UK), a country with a similar health and welfare system.
      Summarising evidence from published studies and national statistics, we found
      that Canada's best successes were in reducing socioeconomic inequalities in early
      learning and child care and reproductive health-specifically in improving equity
      in maternal employment and infant mortality. Comparative data suggest that
      Canada's outcomes in the latter areas were like those in the UK. In contrast,
      Canada's least promising equity outcomes were in relation to health hazard
      control (specifically, tobacco) and child poverty. Though Canada and the UK
      observed similar inequities in smoking, Canada's slow upward trend in child
      poverty prevalence is distinct from the UK's small but steady reduction of child
      poverty. This divergence from the UK's trends indicates that alternative
      investment types and levels may be needed in Canada to achieve similar outcomes
      to those in the UK.

PMID- 30302367
TI  - Comparison of the locations where young adults smoke, vape, and eat/drink
      cannabis: Implications for harm reduction.
AB  - Background: Cannabis vaping and edible use are increasingly popular methods of
      cannabis use. These discreet methods could increase risk of cannabis-related
      problems by facilitating cannabis use in a wider range of settings. Methods: A
      sample of 1018 college students were recruited to complete a survey about their
      health and behavior. Participants who used cannabis in the past year (35.1%, n =
      357) answered questions about their cannabis use, including where they were the
      last time they smoked, vaped, or ate/drank cannabis, and their experience of
      cannabis-related problems. Results: Compared with cannabis smoking, participants
      were more likely to have vaped cannabis (15.8% smoked vs. 24.6% vaped; X2 = 4.59,
      p = .032), and were slightly, but not statistically significantly, more likely to
      have used cannabis edibles (17.5% smoked vs. 24.2% used edibles; X2 = 3.57, p =
      .059), in locations other than a private residence. For example, participants
      were more likely to have vaped cannabis in a car than to have smoked cannabis in
      a car (8.8% vaped vs. 3.5% smoked; X2 = 4.26, p = .039). More frequent cannabis
      vaping was associated with driving while high on cannabis, even after accounting
      for overall frequency of cannabis use and other covariates (OR = 1.22, p = .047).
      More frequent cannabis vaping and edible use were associated with various
      cannabis-related problems, but, in general, these associations became
      statistically non-significant after accounting for overall frequency of cannabis
      use. Conclusions: Cannabis vaporizers and edibles facilitate cannabis use in
      locations that require discretion. Increased availability of cannabis vaporizers
      and edibles could increase risk of cannabis-related problems by enabling use in
      more settings.

PMID- 30302368
TI  - Early affective changes and increased connectivity in preclinical Alzheimer's
      disease.
AB  - Introduction: Affective changes precede cognitive decline in mild Alzheimer's
      disease and may relate to increased connectivity in a "salience network" attuned
      to emotionally significant stimuli. The trajectory of affective changes in
      preclinical Alzheimer's disease, and its relationship to this network, is
      unknown. Methods: One hundred one cognitively normal older adults received
      longitudinal assessments of affective symptoms, then amyloid-PET. We hypothesized
      amyloid-positive individuals would show enhanced emotional reactivity associated
      with salience network connectivity. We tested whether increased global
      connectivity in key regions significantly related to affective changes. Results:
      In participants later found to be amyloid positive, emotional reactivity
      increased with age, and interpersonal warmth declined in women. These individuals
      showed higher global connectivity within the right insula and superior temporal
      sulcus; higher superior temporal sulcus connectivity predicted increasing
      emotional reactivity and decreasing interpersonal warmth. Conclusions: Affective
      changes should be considered an early preclinical feature of Alzheimer's disease.
      These changes may relate to higher functional connectivity in regions critical
      for social-emotional processing.

PMID- 30302369
TI  - Efficacy of temperature-guided cryoballoon ablation without using real-time
      recordings - 12-Month follow-up.
AB  - Background: We sought to evaluate a temperature-guided approach of cryoballoon
      (CB) ablation without visualization of real-time recordings. Methods and results:
      We analysed 166 patients (34.9% female, 60 +/- 11 years) with paroxysmal or short
      term persistent atrial fibrillation (AF). Comorbidities included diabetes
      mellitus (n = 28), coronary artery disease (n = 24), hypertension (n = 122),
      previous stroke or TIA > 3 months (n = 12). Cryoablation of the pulmonary veins
      (PV) was performed using first-generation (n = 78) and second-generation CB (n =
      88). Two 5-minute freezes were performed for the first-generation and two 4
      minute freezes for the second-generation CB with the intention to achieve a
      temperature drop below -40  degrees C. At 12-month follow-up, we observed overall
      freedom from AF in 92 patients (56.6%, mean time to AF recurrence 3.4 +/- 2.9
      months). There was a significant difference in freedom from AF between first
      generation CB (45%) and second-generation CB (67%; p < 0.005). Complications were
      groin hematoma (4.8%) and phrenic nerve palsy (PVP) (2.4%). PVP disappeared after
      12 months in all patients. Three patients developed cardiac tamponade (1.8%) that
      resolved without further sequelae after pericardiocentesis. Multivariate analysis
      revealed that only the achieved temperature in the right inferior PV (RIPV) was a
      predictor of long-term freedom from AF (OR 0.9; p = 0.014). Female gender was a
      predictor of AF recurrence (OR 6.1; p = 0.022). Conclusion: Temperature-guided CB
      ablation without real-time recordings is feasible and safe without reducing the
      efficacy if second-generation CB is used. Deep nadir temperatures especially in
      the RIPV are necessary for long term-success.

PMID- 30302370
TI  - Comment on "A study of association between platelet volume indices and ST
      elevation myocardial infarction".

PMID- 30302371
TI  - Efficacy and tolerability of various bowel preparations in diabetic patients: a
      randomized controlled trial.
AB  - Background and study aims  Diabetes mellitus (DM) is an independent risk factor
      for poor bowel preparation prior to colonoscopy. Bisacodyl is a stimulant
      laxative that may mitigate colonic dysmotility associated with diabetes. We
      hypothesized that adding bisacodyl to split-dose bowel preparation (SDBP) would
      improve the quality of bowel preparation among patients with diabetes. Patients
      and methods  Adult outpatients aged 18 to 80 years undergoing colonoscopy were
      recruited. One hundred and eighty-six patients with diabetes were randomly
      assigned to 1 of 3 treatment arms: 1) conventional 4 L of polyethylene glycol
      electrolyte lavage solution (PEG-ELS; conventional bowel preparation [CBP]); 2)
      split-dose of 4 L PEG-ELS (split-dose bowel preparation [SDBP]); or 3) split-dose
      of 4 L PEG-ELS preceded by 10 mg of oral bisacodyl 10 (SDBP-B). The primary
      outcome measure was bowel cleansing as indicated by Boston Bowel Preparation
      Scale (BBPS) score. Endoscopists were blinded to the preparation used. Secondary
      outcome measures were safety and patient tolerability. Results  Of the 212
      patients randomized, only 186 received assigned bowel preparation. There were no
      differences among the three study groups with regard to age, indication, duration
      of DM, insulin use, narcotic use, or presence of end-organ diabetic
      complications. There was a trend toward better bowel preparation quality among
      those receiving SDBP and SDBP-B compared to those receiving CBP, but the trend
      was not statistically significant  >= 6 BBPS; 67 % vs. 83 % vs. 75 %, P  = 0.1).
      In terms of safety and tolerability, there were no differences among the three
      groups. Conclusion  Adding bisacodyl to SDBP does not improve the quality of
      bowel preparation in patients with DM. Further efforts are needed to optimize
      colonoscopy bowel preparation in this population.

PMID- 30302372
TI  - Evaluation of a 12-mm diameter covered self-expandable end bare metal stent for
      malignant biliary obstruction.
AB  - Background and study aims  Biliary metallic stents are used to drain unresectable
      malignant distal biliary obstructions. This study aimed to evaluate the efficacy
      of a novel 12-mm-diameter covered, self-expandable end bare metal stent (12-mm
      CSEEMS). Patients and methods  We evaluated 99 patients with unresectable
      malignant distal biliary obstructions treated with covered biliary metallic
      stents. Of the 99 patients, 33 underwent 12-mm CSEEMS placement between June 2015
      and April 2017 (12-mm-CSEEMS group) and 66 underwent 10-mm fully-covered self
      expandable metal stent (FCSEMS) placement between January 2010 and July 2015 (10
      mm-FCSEMS group). The overall survival (OS), the recurrent biliary obstruction
      (RBO), cause of RBO, time to RBO (TRBO) and adverse events in 12-mm-CSEEMS group
      and 10-mm-FCSEMS group were evaluated retrospectively. Results  The OS tended to
      be longer in the 12-mm-CSEEMS group (log rank, P  = 0.081) and TRBO was
      significantly longer in the 12-mm-CSEEMS group (log rank, P  = 0.001) than in the
      10-mm-FCSEMS group. Both univariate (HR, 0.449; 95 % CI, 0.27967 - 0.72215; P  =
      0.001) and multivariate (HR, 0.458; 95 % CI, 0.28395 - 0.73744; P  = 0.001) Cox
      hazard analysis found that risk of RBO was significantly lower in 12-mm CSEEMS
      than in 10-mm FCSEMS. There were no significant differences between the 12-mm
      CSEEMS group and 10-mm-FCSEMS group regarding the cause of RBO and adverse
      events. Conclusions  The 12-mm CSEEMS showed a low risk of RBO compared with 10
      mm FCSEMS and was considered to be effective and safe for draining unresectable
      malignant distal biliary obstruction.

PMID- 30302373
TI  - Role of routine upper endoscopy before bariatric surgery in the Middle East
      population: a review of 1278 patients.
AB  - Introduction  The routine use of preoperative endoscopy for patients undergoing
      bariatric surgery is controversial. Although many surgeons find it unnecessary,
      others still consider it a mandatory tool in preoperative assessment. Patients
      and methods  We reviewed the medical records of all patients who had undergone
      preoperative endoscopy before bariatric surgery in Rashid Hospital between
      January 2013 and June 2016. The patients were divided into three groups: Group 0
      included patients with normal endoscopy; Group 1 included patients with
      abnormalities that did not affect the timing or type of procedure; Group 2
      included patients with abnormalities that had a direct impact on the procedure.
      Results  The files of 1473 patients were reviewed. Endoscopy results were not
      present in 195 files, so those patients were excluded, and the remaining 1278
      files were included. The mean age of patients was 41.3 +/- 12.7 years, 61 % were
      female and 39 % were male. The mean body mass index (BMI) was 43.7 +/- 8 kg/m 2 .
      Endoscopy was normal in 10.6 % of patients and abnormal in 89.4 %. The most
      common abnormalities were gastritis, positive Campylobacter-like organism test
      (CLO test), gastroesophageal reflux disease (GERD) with esophagitis and hiatal
      hernia. Group 0 included 10.6 % of patients (n = 135), Group 1 included 25.6 % of
      patients (n = 327), while Group 2 included 63.8 % of patients (n = 816).
      Conclusion  Routine endoscopy seems to play an important part in the preoperative
      preparation of patients planned for bariatric surgery in the Middle East
      population. Further studies or meta-analysis could help in building up clear
      solid evidence and guidelines that could be approved by international bariatric
      associations with regard to indications for preoperative upper endoscopy in
      bariatric patients.

PMID- 30302374
TI  - Linked color imaging improves detection of minimal change esophagitis in non
      erosive reflux esophagitis patients.
AB  - Background and study aims  Non-erosive reflux disease (NERD) includes minimal
      change esophagitis (MCE) and no endoscopic abnormalities. However, for most
      endoscopists, it is difficult to detect MCE with conventional white-light
      endoscopy (WLE). Linked color imaging (LCI) technology is the most recently
      developed image-enhancing technology and improves detection and differentiation
      of subtle mucosal changes using a color contrast method. This study assessed the
      efficacy of WLE combined with LCI for diagnosing MCE compared with WLE. Patients
      and methods  Between February and May 2017, 44 NERD patients and 40 healthy
      subjects were enrolled in our study. First, the distal esophagus was examined
      using WLE followed by LCI. Second, three experienced endoscopists observed all
      the patients' white-light (WL) images and corresponding images of WL and LCI and
      then recorded presence or absence of minimal change esophagitis (MCE +/-). The
      proportion of minimal change between the two groups was then compared. Third,
      five blinded endoscopists with different levels of endoscopic experience assessed
      whether MCE was present. Intraobserver reproducibility and interobserver
      agreement were described using the kappa value. Results  The proportion of MCE in
      the NERD group (70.8 %, 35/48) was higher than that in the control group (22.5 %,
      9/40, P  < 0.001) when diagnosed by the three experienced endoscopists. Detection
      rates for MCE using WLE combined with LCI were higher than those using WLE
      (43/88, 48.9 % vs. 29/88, 33.0 %, P  < 0.001). With WLE combined with LCI,
      intraobserver reproducibility significantly improved, indicating that the
      combined approach can improve interobserver agreement compared with using WLE
      alone. Conclusions  Endoscopic diagnosis of MCE using WLE combined with LCI
      images is effective. Intraobserver reproducibility and interobserver agreement in
      MCE can be improved when LCI is applied with conventional imaging (Clinical trial
      registration number: NCT03068572).

PMID- 30302375
TI  - Insertability comparison of passive bending single-balloon prototype versus
      standard single-balloon enteroscopy: a multicenter randomized non-blinded trial.
AB  - Background and study aims  Traversing the ileocecal valve (ICV) is technically
      challenging with a retrograde approach to single-balloon enteroscopy (SBE). A
      novel technique called responsive insertion technology (RIT) colonoscopy was
      developed to obtain a higher cecal intubation rate in this setting. A prototype
      long SBE equipped with RIT (P-SBE) was developed to obtain superior
      insertability. The aim of this study was to compare the insertability of a
      standard single-balloon enteroscope (S-SBE) versus a P-SBE. Patients and methods 
      This study was a multicenter, randomized, non-blinded, trial of 62 patients with
      small bowel pathologies. All procedures were performed with SBE via the trans
      anal route. Procedure success was defined as stable intubation of the terminal
      ileum (TI) 20 cm beyond the ICV. The primary variable was time to reach stable TI
      intubation 20 cm beyond the ICV (TSTII). If stable TI intubation was not achieved
      within 10 minutes, the initial SBE was removed through the indwelling overtube
      and replaced with another SBE. Results  Sixty patients were examined with two
      patients excluded from this study. TSTII using P-SBE was significantly decreased
      compared to S-SBE (mean P-SBE vs S-SBE: 98.3 vs 169.4 second, P  = 0.006). The
      completion rates for stable intubation within 10 minutes of using P-SBE and S-SBE
      were 96.8 % and 86.2 %, respectively ( P  = 0.19). On endoscope replacement, all
      patients had achieved stable TI intubation. Conclusions  SBE with RIT improves
      insertability when traversing the ileocecal valve in retrograde SBE.

PMID- 30302376
TI  - Differences in upper gastrointestinal neoplasm detection rates based on
      inspection time and esophagogastroduodenoscopy training.
AB  - Background and study aims  Esophagogastroduodenoscopy (EGD) has utility in early
      detection of upper gastrointestinal (UGI) neoplasms. However, previous studies
      report shorter inspection times and inexperienced endoscopists contribute to
      overlooking gastric neoplasms. We investigated neoplasm detection rates according
      to inspection time and extent of EGD training. Patients and methods  In this
      retrospective observational study, we reviewed routine EGDs for 3,925 consecutive
      cases between October 2014 and March 2015. We divided the endoscopists into three
      groups based on median inspection time during EGD without undergoing biopsy.
      Using cut-off median inspection times of 7 and 10 minutes, three, five, and eight
      endoscopists were classified into the fast, moderate, and slow groups,
      respectively. We compared detection rates according to inspection time and the
      extent of EGD training. Results  The median inspection time among all
      endoscopists was 9.3 minutes (range, 6.6 - 12.0 min). The detection rate for UGI
      neoplasms was as follows: fast group, 3.6%; moderate group, 3.3 %; and slow
      group, 3.1 % ( P  = 0.807). The median inspection time was significantly shorter
      among the intensive training >= 1-year group than among the < 1-year group (< 1
      year: median 6.3 min; range 8.2 - 13.9 min, >= 1-year: median 8.9 min; range 6.4 
      11.4 min, P  < 0.001). The detection rate for UGI neoplasms was significantly
      higher among the intensive training >= 1-year group than among the < 1-year group
      (< 1-year: 2.2 %; >= 1-year: 3.7 %, OR = 1.65, 95 % CI: 1.02 - 2.68, P  = 0.041).
      Conclusions  There was no association between inspection times and neoplasm
      detection rates. The quality of EGD, as measured by neoplasm detection rates, may
      be improved by >= 1-year of intensive training.

PMID- 30302377
TI  - Polypoid nodule scar after gastric endoscopic submucosal dissection: results from
      a multicenter study.
AB  - Background and study aims  A post-endoscopic submucosal dissection (ESD) scar is
      expected to look homogeneous, however, some patients develop benign polypoid
      nodule scar (PNS). Incidence of PNS is unknown, yet these scars have direct
      clinical implications because they may render evaluation of post-ESD neoplastic
      recurrence difficult. Therefore, we reviewed the clinical experience of 5 ESD
      referral centers and evaluated their PNS incidence and clinical management.
      Patients and methods  This was a retrospective multicenter case series enrolling
      patients that underwent R0, curative gastric ESD from 2003 to 2015 in 5 academic
      centers. PNS was defined as ESD site nodularity with hyperplastic or regenerative
      tissue histology. Results  A total of 2275 patients underwent gastric ESD with
      endoscopy control and 28 patients (18 men/10 women) developed PNS for overall
      incidence of 1.2 %. Incidence of PNS ranged from 0.15 % to 11.4 % between
      centers. All patients that developed PNS had primary neoplastic lesions located
      in the distal stomach. Considering only lesions situated in the antrum (n = 912),
      incidence of PNS was 3.1 %. After mean follow-up of 43 months (range 6 - 192), no
      malignant recurrence in the PNS has been identified. In five patients (17.8 %)
      PNS disappeared after a mean of 18 months. Conclusion  PNS occurs exclusively
      after ESD in the distal stomach in approximately 3.1 % of patients. Although PNS
      appearance can be concerning, no malignant recurrence was observed after curative
      R0 resection. Therefore, PNS should be viewed as a benign alteration that does
      not require any type of intervention, other than endoscopic surveillance.

PMID- 30302378
TI  - A comparative review of use of sulphate and phosphate salts for colonoscopy
      preparations and their potential for nephrotoxicity.
AB  - Background and study aims  Colonoscopy is a widely used diagnostic procedure
      which requires prior cleansing of the bowel. Many different bowel cleansing
      preparations have been developed, all of which have specific advantages and
      disadvantages. This review compares two low-volume high-osmolarity bowel
      cleansing preparations, oral phosphate salts and oral sulphate salts, with a
      particular focus on risk of nephrotoxicity. Patients and methods  An electronic
      search of the Medline database was performed using the search terms "(phosphates
      OR sulfates) AND cathartics [MeSH Term] AND kidney" restricted to humans with a
      cut-off date of December 31, 2016. Results  Introduction of oral phosphate salts
      offered the advantage of low intake volume and low risk of bowel irritation
      compared to previous options. However, phosphate salts have been associated with
      renal toxicity (acute phosphate nephropathy [APN]), thought to arise due to
      perturbations of calcium and phosphate homeostasis as a consequence of increases
      in serum phosphate. This results in high concentrations of calcium phosphate in
      the distal tubule and collecting ducts of the kidney, where it may precipitate.
      Although APN is rare, it may lead to permanent kidney damage. For this reason,
      phosphate salts are contraindicated in vulnerable patient groups. As an
      alternative to phosphate salts, oral sulphate salts have recently been
      introduced. Because sulphate absorption from the intestinal tract is saturable,
      serum sulphate concentrations increase only minimally after ingestion.
      Furthermore, excretion of sulphate in the kidney is not accompanied by calcium
      excretion and urine calcium levels are unchanged. For these theoretical reasons,
      use of sulphate salts as bowel cleansing solutions is not expected to lead to
      calcium precipitation in the nephron. Conclusions  Oral phosphate salts are no
      longer recommended for routine use as bowel cleansing preparations as they carry
      significant risk of kidney damage and a safer alternative is available in the
      form of oral sulphate solutions. To date, use of sulphate salts has not been
      associated with elevations in serum creatinine or other markers of renal
      impairment, nor with clinical manifestations of kidney injury. Nonetheless,
      experience with sulphate salts in everyday practice is limited and physicians
      should be vigilant in detecting potential safety issues.

PMID- 30302379
TI  - Cap-assisted colonoscopy: a meta-analysis of high-quality randomized controlled
      trials.
AB  - Background and study aims  Standard colonoscopy (SC) is the preferred modality
      for screening for colon cancer; however, it carries a significant polyp/adenoma
      miss rate. Cap-assisted colonoscopy (CC) has been shown to improve polyp/adenoma
      detection rate, decrease cecal intubation time and increase cecal intubation rate
      when compared to standard colonoscopy (SC). However, data on adenoma detection
      rate (ADR) are conflicting. The aim of this meta-analysis was to compare the
      performance of CC with SC for ADR among high-quality randomized controlled
      trials. Patients and methods  We performed an extensive literature search using
      MEDLINE, EMBASE, Scopus, Cochrane and Web of Science databases and abstracts
      published at national meetings. Only comparative studies between CC and SC were
      included if they reported ADR, adenoma per person (APP), cecal intubation rate,
      and cecal intubation time. The exclusion criterion for comparing ADR was studies
      with Jadad score <= 2. The odds ratio (OR) was calculated using Mantel-Haenszel
      method. I 2 test was used to measure heterogeneity among studies. Results 
      Analysis of high-quality studies (Jadad score >= 3, total of 7 studies) showed
      that use of cap improved the ADR with the results being statistically significant
      (OR 1.18, 95 % CI 1.03 - 1.33) and detection of 0.16 (0.02 - 0.30) additional
      APP. The cecal intubation rate in the CC group was 96.3 % compared to 94.5 % with
      SC (total of 17 studies). Use of cap improved cecal intubation (OR 1.61, 95 % CI
      1.33 - 1.95) when compared to SC ( P value < 0.001). Use of cap decreased cecal
      intubation time by an average of 0.88 minutes (95 % CI 0.37 - 1.39) or 53
      seconds. Conclusions  Meta-analysis of high-quality studies showed that CC
      improved the ADR compared to SC.

PMID- 30302380
TI  - Endoscopic full-thickness resection in the colorectum: a single-center case
      series evaluating indication, efficacy and safety.
AB  - Background and study aims  Endoscopic full-thickness resection (eFTR) allows en
      bloc and transmural resection of colorectal lesions for which other advanced
      endoscopic techniques are unsuitable. We present our experience with a novel
      "clip first, cut later" eFTR-device and evaluate its indications, efficacy and
      safety. Patients and methods  From July 2015 through October 2017, 51 eFTR
      procedures were performed in 48 patients. Technical success and R0-resection
      rates were prospectively recorded and retrospectively analyzed. Results 
      Indications for eFTR were non-lifting adenoma (n = 19), primary resection of
      malignant lesion (n = 2), resection of scar tissue after incomplete endoscopic
      resection of low-risk T1 colorectal carcinoma (n = 26), adenoma involving a
      diverticulum (n = 2) and neuroendocrine tumor (n = 2). Two lesions were treated
      by combining endoscopic mucosal resection and eFTR. Technical success was
      achieved in 45 of 51 procedures (88 %). Histopathology confirmed full-thickness
      resection in 43 of 50 specimens (86 %) and radical resection (R0) in 40
      procedures (80 %). eFTR-specimens, obtained for indeterminate previous T1
      colorectal carcinoma resection, were free of residual carcinoma in 25 of 26 cases
      (96 %). In six patients (13 %) a total of eight adverse events occurred within 30
      days after eFTR. One perforation occurred, which was corrected endoscopically. No
      emergency surgery was necessary. Conclusion  In this study eFTR appears to be
      safe and effective for the resection of colorectal lesions. Technical success, R0
      resection and major adverse events rate were reasonable and comparable with eFTR
      data reported elsewhere. Mean specimen diameter (23 mm) limits its use to
      relatively small lesions. A clinical algorithm for eFTR case selection is
      proposed. eFTR ensured local radical excision where other endoscopic techniques
      did not suffice and reduced the need for surgery in selected cases.

PMID- 30302381
TI  - Evaluation of a new pan-enteric video capsule endoscopy system in patients with
      suspected or established inflammatory bowel disease - feasibility study.
AB  - Background and study aims  Inflammatory bowel disease (IBD) affects the small
      bowel and colon. Endoscopic evaluation of these organs is essential. The new pan
      enteric Crohn's capsule (PCC) system is customized for complete coverage of IBD
      lesions in the entire bowel, allowing assessment and follow-up of disease
      severity and extent. The aim of this study was to evaluate the functionality of
      the PCC system in patients with suspected or established IBD. Patients and
      methods  This was a prospective five-center feasibility study assessing the
      performance of PCC. Subjects ingested PCC after patency assurance with standard
      bowel preparation plus boosts. The primary endpoint was successful procedure,
      that is, video creation and report generation in accordance with methodology.
      Secondary endpoints were subjective coverage of the entire bowel, duration of
      reading time, video quality and occurrence of adverse events. Results  Forty-one
      patients were included in the study with a mean age of 40.8 years +/- 15.5, 46 %
      of whom were males. Seventy-one percent of patients had established Crohn's
      disease (CD) and 53 % had active disease. Cleansing was graded good/excellent in
      95 %. All 41 videos met the primary endpoint. There was no retention, 83 %
      reached the toilet while still recording. Thirty-one percent of patients with CD
      had proximal disease. Bowel coverage was graded 6.7 +/- 0.6 and 6.1 +/- 1.3 (1 -
      7, unconfident - confident), image quality 6.1 +/- 0.8 (1 - 7, poor - excellent),
      and reading time 3.7 +/- 1.4 (1 - 7, very short to very long). Conclusions  The
      PCC system is a minimally invasive system allowing extensive evaluation of the
      entire bowel in patients with IBD.

PMID- 30302382
TI  - Partnership with African Countries: European Society of Gastrointestinal
      Endoscopy (ESGE) - Position Statement.
AB  - A new objective for the European Society of Gastrointestinal Endoscopy (ESGE) is
      to develop long-term partnerships with African countries. For this, an
      International Affairs Working Group (IAWG) was formed. In conjunction with the
      World Endoscopy Organization (WEO), ESGE conducted a survey of gastrointestinal
      (GI) endoscopy in Africa. Survey results showed that many African countries have
      few GI endoscopy centers with adequate resources. Barriers to the development of
      endoscopy services include a shortage of endoscopists who have undergone advanced
      endoscopy training, and a lack of equipment and basic infrastructure. Diseases
      related to infectious etiology are more prevalent than neoplastic diseases in
      Africa. Any development of endoscopy services needs to consider the local
      prevalence of diseases for which GI endoscopy is required, as well as the
      availability of resources. The IAWG will initiate a cascade approach to identify
      and adapt ESGE guidelines for local use. The guidelines will consider the level
      of resources available for each intervention, as well as cost, infrastructure,
      and training, and will be approved by consensus of local experts who are
      representative of different African areas. Suitable centers in African countries
      will be identified, and in future will be developed into WEO/ESGE training
      centers, to provide local training in both basic and advanced endoscopy according
      to the needs of the area.

PMID- 30302383
TI  - Nonvariceal upper gastrointestinal hemorrhage: European Society of
      Gastrointestinal Endoscopy (ESGE) Cascade Guideline.

PMID- 30302384
TI  - Reply to Schurr and Gottwald.

PMID- 30302386
TI  - Spot diagnosis of intermittent gastrointestinal bleeding.
AB  - Background and study aims  In this case report with video, we present a unique
      image of a rare, but important cause of gastrointestinal bleeding which often is
      missed due to its intermittent nature.

PMID- 30302385
TI  - Safety and rate of delayed adverse events with lumen-apposing metal stents (LAMS)
      for pancreatic fluid collections: a multicenter study.
AB  - Background and study aims  Endoscopic drainage with dedicated lumen-apposing
      metal stents (LAMS) is routinely performed for symptomatic pancreatic fluid
      collections (PFCs), walled-off necrosis (WON) and pseudocyst (PP). There has been
      increasing concern regarding delayed adverse events associated with the
      indwelling LAMS.  Patients and methods  Multicenter retrospective analysis of
      consecutive patients who underwent endoscopic ultrasound (EUS)-guided LAMS
      placement for PFC from January 2010 to May 2017. Main outcomes included: (1)
      resolution of the PFC, (2) rate of delayed adverse events at follow-up, and (3)
      predictors of treatment failure and delayed adverse events on logistic
      regression. Results  A total of 122 patients (mean age 50.9 years, 68 % male)
      underwent LAMS insertion for 64 WON (98.4 %) and 58 PP (98.3 %). PFC mean size
      was 10.6 cm. PFC resolution was significantly lower for WON (62.3 %) vs. PP (96.5
      %) ( P  < 0.001) on imaging at a median of 4 weeks. Stent occlusion was
      identified in 18 (29.5 %) and 10 (17.5 %) patients with WON and PP, respectively
      ( P  = 0.13). There were no cases of delayed bleeding or buried stent on follow
      up endoscopy. Use of electrocautery-enhanced LAMS was the only factor associated
      with treatment failure of WON (OR = 13.2; 95 % ci: 3.33 - 51.82, P  = 0.02) on
      logistic regression. There were no patient, operator, or procedure-related
      factors predictive of stent occlusion. Conclusions  EUS-guided LAMS for PFC is
      associated with a low incidence of delayed adverse events. While nearly all PPs
      resolve at 4 weeks permitting LAMS removal shortly thereafter, many WON persist,
      with use of electrocautery-enhanced LAMS being the sole predictor of treatment
      failure.

PMID- 30302387
TI  - EUS fine-needle pancreatic core biopsy can determine eligibility for tumor
      agnostic immunotherapy.
AB  - Background and study aims  The US FDA recently approved a cancer treatment with
      pembrolizumab based upon the tumor biomarker status of deficient mismatch repair
      (dMMR) rather than a specific disease-based approach. We sought to determine if
      endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) could determine dMMR
      and quantification of PD-L1 expression to potentially guide the delivery of tumor
      agnostic immunotherapy. Patients and methods  Immunohistochemistry was performed
      on archived pancreas core biopsy specimens. Tumors with absent nuclear staining
      of DNA mismatch repair proteins represented dMMR. Tumors were considered to have
      any or high PD-L1 expression, if expressed in >= 1 % or >= 50 % of tumor cells.
      Results  Histologic specimen adequacy for MMR status assessment was satisfactory
      in 97.2 % of tumors. dMMR and high PD-L1 expression was identified in 3 % and 8.1
      % of the cohort. Conclusion  In the setting of tumor type agnostic immunotherapy,
      it is projected that at least 3 % of malignant pancreas lesions will be sensitive
      to pembrolizumab and up to 8 % sensitive to the family of immune checkpoint
      inhibitors. This highlights the expanding role of EUS-FNB in the field of
      precision immuno-oncology.

PMID- 30302388
TI  - Behavioral Phenotyping of an Improved Mouse Model of Phelan-McDermid Syndrome
      with a Complete Deletion of the Shank3 Gene.
AB  - Phelan-McDermid syndrome (PMS) is a rare genetic disorder in which one copy of
      the SHANK3 gene is missing or mutated, leading to a global developmental delay,
      intellectual disability (ID), and autism. Multiple intragenic promoters and
      alternatively spliced exons are responsible for the formation of numerous
      isoforms. Many genetically-modified mouse models of PMS have been generated but
      most disrupt only some of the isoforms. In contrast, the vast majority of known
      SHANK3 mutations found in patients involve deletions that disrupt all isoforms.
      Here, we report the production and thorough behavioral characterization of a new
      mouse model in which all Shank3 isoforms are disrupted. Domains and tasks
      examined in adults included measures of general health, neurological reflexes,
      motor abilities, sensory reactivity, social behavior, repetitive behaviors,
      cognition and behavioral inflexibility, and anxiety. Our mice are more severely
      affected than previously published models. While the deficits were typically more
      pronounced in homozygotes, an intermediate phenotype was observed for
      heterozygotes in many paradigms. As in other Shank3 mouse models, stereotypies,
      including increased grooming, were observed. Additionally, sensory alterations
      were detected in both neonatal and adult mice, and motor behavior was strongly
      altered, especially in the open field and rotarod locomotor tests. While social
      behaviors measured with the three-chambered social approach and male-female
      interaction tests were not strongly impacted, Shank3-deficient mice displayed a
      strong escape behavior and avoidance of inanimate objects in novel object
      recognition, repetitive novel object contact, marble burying, and nest building
      tasks, indicating increased novelty-induced anxiety. Similarly, increased
      freezing was observed during fear conditioning training and amygdala-dependent
      cued retrieval. Finally, deficits were observed in both initial training and
      reversal in the Barnes maze and in contextual fear testing, which are memory
      tasks involving hippocampal-prefrontal circuits. In contrast, working memory in
      the Y-maze spontaneous alternation test was not altered. This new mouse model of
      PMS, engineered to most closely represent human mutations, recapitulates core
      symptoms of PMS providing improvements for both construct and face validity,
      compared to previous models.

PMID- 30302389
TI  - Selective Effects of the Loss of NMDA or mGluR5 Receptors in the Reward System on
      Adaptive Decision-Making.
AB  - Selecting the most advantageous actions in a changing environment is a central
      feature of adaptive behavior. The midbrain dopamine (DA) neurons along with the
      major targets of their projections, including dopaminoceptive neurons in the
      frontal cortex and basal ganglia, play a key role in this process. Here, we
      investigate the consequences of a selective genetic disruption of NMDA receptor
      and metabotropic glutamate receptor 5 (mGluR5) in the DA system on adaptive
      choice behavior in mice. We tested the effects of the mutation on performance in
      the probabilistic reinforcement learning and probability-discounting tasks. In
      case of the probabilistic choice, both the loss of NMDA receptors in dopaminergic
      neurons or the loss mGluR5 receptors in D1 receptor-expressing dopaminoceptive
      neurons reduced the probability of selecting the more rewarded alternative and
      lowered the likelihood of returning to the previously rewarded alternative (win
      stay). When observed behavior was fitted to reinforcement learning models, we
      found that these two mutations were associated with a reduced effect of the
      expected outcome on choice (i.e., more random choices). None of the mutations
      affected probability discounting, which indicates that all animals had a normal
      ability to assess probability. However, in both behavioral tasks animals with
      targeted loss of NMDA receptors in dopaminergic neurons or mGluR5 receptors in D1
      neurons were significantly slower to perform choices. In conclusion, these
      results show that glutamate receptor-dependent signaling in the DA system is
      essential for the speed and accuracy of choices, but at the same time probably is
      not critical for correct estimation of probable outcomes.

PMID- 30302390
TI  - Adaptation and Inhibition Control Pathological Synchronization in a Model of
      Focal Epileptic Seizure.
AB  - Pharmacoresistant epilepsy is a common neurological disorder in which increased
      neuronal intrinsic excitability and synaptic excitation lead to pathologically
      synchronous behavior in the brain. In the majority of experimental and
      theoretical epilepsy models, epilepsy is associated with reduced inhibition in
      the pathological neural circuits, yet effects of intrinsic excitability are
      usually not explicitly analyzed. Here we present a novel neural mass model that
      includes intrinsic excitability in the form of spike-frequency adaptation in the
      excitatory population. We validated our model using local field potential (LFP)
      data recorded from human hippocampal/subicular slices. We found that synaptic
      conductances and slow adaptation in the excitatory population both play essential
      roles for generating seizures and pre-ictal oscillations. Using bifurcation
      analysis, we found that transitions towards seizure and back to the resting state
      take place via Andronov-Hopf bifurcations. These simulations therefore suggest
      that single neuron adaptation as well as synaptic inhibition are responsible for
      orchestrating seizure dynamics and transition towards the epileptic state.

PMID- 30302392
TI  - 'Levodopa Phobia': a review of a not uncommon and consequential phenomenon.
AB  - 'Levodopa Phobia' is under-recognised in Parkinson's disease but can cause
      profound detrimental clinical complications if left to continue. Several types
      can be encountered in clinical practice and can be driven by a misplaced fear of
      levodopa-induced dyskinesias, other gastrointestinal side effects and also the
      theoretical notion that levodopa may be toxic to dopaminergic neurons in the
      brain. The condition can be underpinned by a sense of strong influence from the
      physicians or carers who are unwilling to prescribe or consider levodopa, and
      also high levels of anxiety or even impulsive compulsive traits in patients who
      have been influenced by available literature or social media-based information.
      If unrecognised, the clinical issue may lead to motor deterioration and related
      muscle contractures leading to social isolation as well as a range of non-motor
      symptoms. In some, there may be emergence of intrusive impulse control disorders
      because of reliance on only dopamine agonists related to the fear of taking
      levodopa. Four cases illustrate the different patterns of 'Levodopa Phobia' in
      this study. Management of levodopa phobia is complex and includes recognition and
      skilled neuropsychological interventions to break the misperceptions about the
      complications of levodopa therapy.

PMID- 30302391
TI  - Ingestion of subthreshold doses of environmental toxins induces ascending
      Parkinsonism in the rat.
AB  - Increasing evidence suggests that environmental neurotoxicants or misfolded alpha
      synuclein generated by such neurotoxicants are transported from the
      gastrointestinal tract to the central nervous system via the vagus nerve,
      triggering degeneration of dopaminergic neurons in the substantia nigra pars
      compacta (SNpc) and causing Parkinson's disease (PD). We tested the hypothesis
      that gastric co-administration of subthreshold doses of lectins and paraquat can
      recreate the pathology and behavioral manifestations of PD in rats. A solution
      containing paraquat + lectin was administered daily for 7 days via gastric
      gavage, followed by testing for Parkinsonian behavior and gastric dysmotility. At
      the end of the experiment, brainstem and midbrain tissues were analyzed for the
      presence of misfolded alpha-synuclein and neuronal loss in the SNpc and in the
      dorsal motor nucleus of the vagus (DMV). Misfolded alpha-synuclein was found in
      DMV and SNpc neurons. A significant decrease in tyrosine hydroxylase positive
      dopaminergic neurons was noted in the SNpc, conversely there was no apparent loss
      of cholinergic neurons of the DMV. Nigrovagally-evoked gastric motility was
      impaired in treated rats prior to the onset of parkinsonism, the motor deficits
      of which were improved by l-dopa treatment. Vagotomy prevented the development of
      parkinsonian symptoms and constrained the appearance of misfolded alpha-synuclein
      to myenteric neurons. These data demonstrate that co-administration of
      subthreshold doses of paraquat and lectin induces progressive, l-dopa-responsive
      parkinsonism that is preceded by gastric dysmotility. This novel preclinical
      model of environmentally triggered PD provides functional support for Braak's
      staging hypothesis of idiopathic PD.

PMID- 30302393
TI  - The effect of mild decrement in plasma volume simulating short-duration
      spaceflight on intracranial pressure.
AB  - Short-duration spaceflight induces an approximately 10% reduction in plasma
      volume, which leads to mild volume depletion. In a previous study, we found that
      mild volume depletion improved dynamic cerebral autoregulation. However, the
      effect of mild volume depletion on intracranial pressure (ICP) remains unknown.
      Therefore, we estimated ICP noninvasively (nICP), and calculated two indices
      relating to ICP, the cerebral artery compliance and the cerebral blood flow
      pulsatility index (PI), to examine whether ICP would decrease due to a mild
      decrement in plasma volume. In our previous experiment, fourteen subjects were
      administered 0.2 mg/kg of furosemide in a supine position to simulate an
      approximately 10% reduction in plasma volume induced by short-duration
      spaceflight. We re-analyzed the cerebral blood flow velocity waveform from the
      middle cerebral artery obtained by transcranial Doppler and the arterial blood
      pressure waveform at the radial artery obtained by tonometry to estimate nICP and
      to calculate cerebral artery compliance and PI using mathematical analysis based
      on an intracranial hydraulic model. All indices were compared between before and
      after furosemide administration. There were no significant changes in nICP and
      cerebral artery compliance. However, PI decreased significantly from before to
      after furosemide administration (0.78 +/- 0.10 to 0.74 +/- 0.09, p = 0.009).
      Decreases in ICP were not observed during the 10% reduction in plasma volume.
      Although cerebral artery compliance did not change, PI decreased significantly.
      These findings suggest that the impedance of distal cerebral arteries would be
      reduced in response to mild decreases in plasma volume induced by short-duration
      spaceflight.

PMID- 30302395
TI  - Adaptation of the Roseman 6-Point Mastery Learning Model to the College of
      Medicine Program.
AB  - Medical education has evolved over time toward a model which integrates clinical
      medicine with the basic sciences. More recently, medical education has put an
      emphasis on outcome-based education. Other areas of health care education have
      had a similar emphasis which can provide models to inform a new model for medical
      education. The Roseman University of Health Sciences has developed and
      implemented a model based on underlying tenets of mastery learning since 1999.
      The model has been implemented in pharmacy, nursing, and dental education. It was
      conceived as an integration of 6 key points which reinforce each other and
      interrelate to support learning. The model has been modified for application to
      medical education in support of medical education's outcome-based emphasis and to
      address the educational demands of the changing environment of the practice of
      medicine.

PMID- 30302394
TI  - Activation and Utilization of an Electronic Health Record Patient Portal at an
      Academic Medical Center-Impact of Patient Demographics and Geographic Location.
AB  - The advent of the online electronic health record patient portal has provided an
      efficient and practical means for patients to become more involved in their
      health care. In this report, we analyze how demographic variables such as age,
      gender, race, and geographic location affect patient portal activation and usage
      at the University of Iowa Hospitals and Clinics, the sole academic medical center
      in the state of Iowa, a predominantly rural state. Our primary end points were
      activation of the patient portal (MyChart, Epic, Inc) and access of outpatient
      laboratory and radiology results, among the most commonly accessed and popular
      features of the patient portal. We thus analyzed data from 536 378 patients to
      determine rates of patient portal activation and data from 219 671 patient
      encounters to determine the frequency at which patients access their online
      diagnostic test results. Higher rates of patient portal activation and usage were
      associated with female gender, Caucasians/non-underrepresented minorities,
      geographic location in closer proximity to the medical center (Iowa City and
      neighboring cities/suburbs), and nonelderly adults. For underrepresented minority
      and rural patients, opportunities for improvement exist for both activation and
      more robust use of online patient portal accounts. Overall, these data highlight
      existing disparities with online patient portal usage and provide a base on which
      further studies and interventions can help to improve utilization of these
      systems.

PMID- 30302396
TI  - Effects of Advanced Cardiac Procedure Simulator Training on Learning and
      Performance in Cardiovascular Medicine Fellows.
AB  - Background: Simulation-based training has been used in medical training
      environments to facilitate the learning of surgical and minimally invasive
      techniques. We hypothesized that integration of a procedural simulation
      curriculum into a cardiology fellowship program may be educationally beneficial.
      Methods: We conducted an 18-month prospective study of cardiology trainees at
      Vanderbilt University Medical Center. Two consecutive classes of first-year
      fellows (n = 17) underwent a teaching protocol facilitated by simulated cases and
      equipment. We performed knowledge and skills evaluations for 3 procedures
      (transvenous pacing [TVP] wire, intra-aortic balloon pump [IABP], and
      pericardiocentesis [PC]). The index class of fellows was reevaluated at 18 months
      postintervention to measure retention. Using nonparametric statistical tests, we
      compared assessments of the intervention group, at the time of intervention and
      18 months, with those of third-year fellows (n = 7) who did not receive simulator
      based training. Results: Compared with controls, the intervention cohort had
      higher scores on the postsimulator written assessment, TVP skills assessment, and
      IABP skills assessment (P = .04, .007, and .02, respectively). However, there was
      no statistically significant difference in scores on the PC skills assessment
      between intervention and control groups (P = .08). Skills assessment scores for
      the intervention group remained higher than the controls at 18 months (P = .01,
      .004, and .002 for TVP, IABP, and PC, respectively). Participation rate was 100%
      (24/24). Conclusions: Procedural simulation training may be an effective tool to
      enhance the acquisition of knowledge and technical skills for cardiology
      trainees. Future studies may address methods to improve performance retention
      over time.

PMID- 30302397
TI  - Emerging role of precision medicine in biliary tract cancers.
AB  - Biliary tracts cancers (BTCs) are a diverse group of aggressive malignancies with
      an overall poor prognosis. Genomic characterization has uncovered many putative
      clinically actionable aberrations that can also facilitate the prognostication of
      patients. As such, comprehensive genomic profiling is playing a growing role in
      the clinical management of BTCs. Currently however, there is only one precision
      medicine approved by the US Food and Drug Administration (FDA) for the treatment
      of BTCs. Herein, we highlight the prevalence and prognostic, diagnostic, and
      predictive significance of recurrent mutations and other genomic aberrations with
      current clinical implications or emerging relevance to clinical practice. Some
      ongoing clinical trials, as well as future areas of exploration for precision
      oncology in BTCs are highlighted.

PMID- 30302398
TI  - A minimal helical-hairpin motif provides molecular-level insights into misfolding
      and pharmacological rescue of CFTR.
AB  - Our meagre understanding of CFTR misfolding and its reversal by small-molecule
      correctors hampers the development of mechanism-based therapies of cystic
      fibrosis. Here we exploit a helical-hairpin construct-the simplest proxy of
      membrane-protein tertiary contacts-containing CFTR's transmembrane helices 3 and
      4 and its corresponding disease phenotypic mutant V232D to gain molecular-level
      insights into CFTR misfolding and drug rescue by the corrector Lumacaftor. Using
      a single-molecule FRET approach to study hairpin conformations in lipid bilayers,
      we find that the wild-type hairpin is well folded, whereas the V232D mutant
      assumes an open conformation in bilayer thicknesses mimicking the endoplasmic
      reticulum. Addition of Lumacaftor reverses the aberrant opening of the mutant
      hairpin to restore a compact state as in the wild type. The observed membrane
      escape of the V232D hairpin and its reversal by Lumacaftor complement cell-based
      analyses of the full-length protein, thereby providing in vivo and in vitro
      correlates of CFTR misfolding and drug-action mechanisms.

PMID- 30302399
TI  - Doxorubicin induces caspase-mediated proteolysis of KV7.1.
AB  - Kv7.1 (KCNQ1) coassembles with KCNE1 to generate the cardiac IKs -channel. Gain-
      and loss-of-function mutations in KCNQ1 are associated with cardiac arrhthymias,
      highlighting the importance of modulating IKs activity for cardiac function.
      Here, we report proteolysis of Kv7.1 as an irreversible posttranslational
      modification. The identification of two C-terminal fragments of Kv7.1 led us to
      identify an aspartate critical for the generation of one of the fragments and
      caspases as responsible for mediating proteolysis. Activating caspases reduces
      Kv7.1/KCNE1 currents, which is abrogated in cells expressing caspase-resistant
      channels. Enhanced cleavage of Kv7.1 can be detected for the LQT mutation G460S,
      which is located adjacent to the cleavage site, whereas a calmodulin-binding
      deficient mutation impairs cleavage. Application of apoptotic stimuli or
      doxorubicin-induced cardiotoxicity provokes caspase-mediated cleavage of
      endogenous IKs in human cardiomyocytes. In summary, caspases are novel regulatory
      components of IKs channels that may have important implications for the molecular
      mechanism of doxorubicin-induced cardiotoxicity.

PMID- 30302400
TI  - Pinopsin evolved as the ancestral dim-light visual opsin in vertebrates.
AB  - Pinopsin is the opsin most closely related to vertebrate visual pigments on the
      phylogenetic tree. This opsin has been discovered among many vertebrates, except
      mammals and teleosts, and was thought to exclusively function in their brain for
      extraocular photoreception. Here, we show the possibility that pinopsin also
      contributes to scotopic vision in some vertebrate species. Pinopsin is
      distributed in the retina of non-teleost fishes and frogs, especially in their
      rod photoreceptor cells, in addition to their brain. Moreover, the retinal
      chromophore of pinopsin exhibits a thermal isomerization rate considerably lower
      than those of cone visual pigments, but comparable to that of rhodopsin.
      Therefore, pinopsin can function as a rhodopsin-like visual pigment in the
      retinas of these lower vertebrates. Since pinopsin diversified before the
      branching of rhodopsin on the phylogenetic tree, two-step adaptation to scotopic
      vision would have occurred through the independent acquisition of pinopsin and
      rhodopsin by the vertebrate lineage.

PMID- 30302401
TI  - 2D polarization imaging as a low-cost fluorescence method to detect alpha
      synuclein aggregation ex vivo in models of Parkinson's disease.
AB  - A hallmark of Parkinson's disease is the formation of large protein-rich
      aggregates in neurons, where alpha-synuclein is the most abundant protein. A
      standard approach to visualize aggregation is to fluorescently label the proteins
      of interest. Then, highly fluorescent regions are assumed to contain aggregated
      proteins. However, fluorescence brightness alone cannot discriminate micrometer
      sized regions with high expression of non-aggregated proteins from regions where
      the proteins are aggregated on the molecular scale. Here, we demonstrate that 2
      dimensional polarization imaging can discriminate between preformed non
      aggregated and aggregated forms of alpha-synuclein, and detect increased
      aggregation in brain tissues of transgenic mice. This imaging method assesses
      homo-FRET between labels by measuring fluorescence polarization in excitation and
      emission simultaneously, which translates into higher contrast than fluorescence
      anisotropy imaging. Exploring earlier aggregation states of alpha-synuclein using
      such technically simple imaging method could lead to crucial improvements in our
      understanding of alpha-synuclein-mediated pathology in Parkinson's Disease.

PMID- 30302404
TI  - Phytochemical analysis of Canna indica L. roots and rhizomes extract.
AB  - Canna indica L. (Cannaceae) roots and rhizomes were reported to possess various
      biological properties like antimicrobial, anthelmintic potential and HIV-1
      reverse transcriptase inhibition. In our previous studies, they showed
      antidiabetic activity on normal rats and rats co-addicted with caffeine and
      nicotine. In the pursuit of the phytochemical/s responsible for these biological
      activities, present study was aimed at phytochemical evaluation of hydroalcoholic
      extract (HAE) of C. indica L. roots and rhizomes; including preliminary
      screening, thin layer chromatography, H1-NMR and HR-LC/MS-MS analysis. After
      preliminary detection of flavonoids, tannins and sterols, HAE was tested for
      presence of beta-sitosterol using TLC. H1-NMR spectrum of HAE revealed the
      presence of around 761 deshielded protons corresponding to different polar
      compounds. HR-LC/MS-MS analysis carried out at both positive and negative ion
      mode, indicated the presence of more than 90 compounds including short fragment
      of peptide. As per METLIN database, predicted major phytochemicals were 3'
      hydroxytrimethoprim, 3,7-epoxycaryophyllan-6-one, swietenine, typhasterol,
      hexacosanedioic acid and 3beta, 6alpha,7alpha-trihydroxy-5beta-cholan-24-oic acid
      few of which, are biologically active.

PMID- 30302402
TI  - Genetically engineered minipigs model the major clinical features of human
      neurofibromatosis type 1.
AB  - Neurofibromatosis Type 1 (NF1) is a genetic disease caused by mutations in
      Neurofibromin 1 (NF1). NF1 patients present with a variety of clinical
      manifestations and are predisposed to cancer development. Many NF1 animal models
      have been developed, yet none display the spectrum of disease seen in patients
      and the translational impact of these models has been limited. We describe a
      minipig model that exhibits clinical hallmarks of NF1, including cafe au lait
      macules, neurofibromas, and optic pathway glioma. Spontaneous loss of
      heterozygosity is observed in this model, a phenomenon also described in NF1
      patients. Oral administration of a mitogen-activated protein kinase/extracellular
      signal-regulated kinase inhibitor suppresses Ras signaling. To our knowledge,
      this model provides an unprecedented opportunity to study the complex biology and
      natural history of NF1 and could prove indispensable for development of imaging
      methods, biomarkers, and evaluation of safety and efficacy of NF1-targeted
      therapies.

PMID- 30302403
TI  - Alcohol reduces muscle fatigue through atomistic interactions with nicotinic
      receptors.
AB  - Alcohol consumption affects many organs and tissues, including skeletal muscle.
      However, the molecular mechanism of ethanol action on skeletal muscle remains
      unclear. Here, using molecular dynamics simulations and single channel
      recordings, we show that ethanol interacts with a negatively charged amino acid
      within an extracellular region of the neuromuscular nicotinic acetylcholine
      receptor (nAChR), thereby altering its global conformation and reducing the
      single channel current amplitude. Charge reversal of the negatively charged amino
      acid abolishes the nAChR-ethanol interaction. Moreover, using transgenic animals
      harboring the charge-reversal mutation, ex vivo measurements of muscle force
      production show that ethanol counters fatigue in wild type but not homozygous
      alphaE83K mutant animals. In accord, in vivo studies of motor coordination
      following ethanol administration reveal an approximately twofold improvement for
      wild type compared to homozygous mutant animals. Together, the converging results
      from molecular to animal studies suggest that ethanol counters muscle fatigue
      through its interaction with neuromuscular nAChRs.

PMID- 30302405
TI  - The transcriptional response of mouse spleen B cells to IL-4: Comparison to the
      response of human peripheral blood B cells.
AB  - The Th2 cytokine IL-4 triggers a signaling cascade which activates transcription
      by STAT6. The goals of the present study are to define the transcriptomic
      response of mouse spleen B cells (mSBC) to IL-4 used as single stimulus, its
      specificity compared to human peripheral blood B cells (hPBBC) and to mouse
      spleen T cells (mSTC), and the pathways affected. Oligonucleotide-based
      microarrays were performed using two references, the untreated sample and the
      cells cultured without IL-4, an experimental design which reduces the potential
      confounding effect of cellular stress during culture. Specificity was addressed
      by comparing the response of mSBC and our previously published study on hPBBC, of
      similar design, and a study by other authors on mSTC. We detected an mSBC
      specific response (including novel genes, e.g., Sertad4, Lifr, Pmepa1, Epcam,
      Tbxas1; and common genes, e.g., Usp2, Cst7, Grtp1, and Casp6), an hPBBC-specific
      response (e.g., CCL17, MTCL1, GCSAM, HOMER2, IL2RA), and a common mSBC/hPBBC
      response (e.g., CISH, NFIL3, SOCS1, VDR, CDH1). In contrast, the mSBC and mSTC
      responses were largely divergent. Gene set enrichment analysis (GSEA) was applied
      for the first time to identify the pathways affected. Both in mSBC and hPBBC, IL
      4 activated Myc, the transcriptional machinery itself, cell cycle, mitochondria
      and respiratory chain, ribosome, proteasome and antigen presentation, and Wnt
      signaling, and inhibited GPCR signaling. However, significant differences were
      found in histone demethylation, Nod signaling, and Rho signaling, which were
      downregulated in mSBC, and in chromatin condensation, which was downregulated in
      hPBBC. These findings may have therapeutic implications for the treatment of
      allergic diseases and parasitic infections.

PMID- 30302406
TI  - Prophylactic procedure tract radiotherapy for malignant pleural mesothelioma: A
      systematic review and meta-analysis.
AB  - Background and purpose: Malignant pleural mesothelioma (MPM) is an aggressive
      cancer with a propensity for seeding procedure tracts, leading to symptomatic
      metastases. There is conflicting evidence on the value of prophylactic procedure
      tract radiotherapy in reducing tract metastases. We performed a systematic review
      and meta-analysis to estimate the benefit of radiotherapy in this setting.
      Materials and methods: Electronic databases were searched to January 1, 2018 for
      prospective randomized control trials with prophylactic procedure tract
      radiotherapy as the intervention arm. Pooled odds ratios and 95% confidence
      intervals were calculated using a random effects model. Study heterogeneity was
      assessed using the I2 statistic, and publication bias was evaluated by funnel
      plot and Egger's regression model. Results: Five studies were included for meta
      analysis. Prophylactic radiotherapy did not have a statistically significant
      reduction on the risk of procedure site recurrence, with a pooled relative risk
      of 0.69 (95% CI 0.33-1.43). There was moderate heterogeneity between trials. All
      trials were assessed as moderate or high risk of bias overall. Conclusion: This
      systematic review has confirmed that there is no role for prophylactic procedure
      tract radiotherapy in MPM. In the absence of effective prophylactic procedures,
      patients need to be monitored closely, and palliative interventions delivered in
      a timely manner to reduce morbidity associated with procedure tract metastases.

PMID- 30302408
TI  - Absorption coefficient of carbon dioxide across atmospheric troposphere layer.
AB  - Absorption coefficient affected by carbon dioxide concentration and optical path
      length responsible for temperature or global warming across the troposphere
      layer, which is less than the altitude of 10 km in the atmosphere, is
      systematically presented in this work. Solar irradiation within a short
      wavelength range can be absorbed, scattered and transmitted by the atmosphere,
      and absorbed and reflected by the Earth's surface. Radiative emission in high
      wavelength ranges from the Earth's surface at low temperature can be absorbed by
      atmospheric water vapor, carbon dioxide and other gases. Unbalance of radiation
      thus results in the atmosphere to act as the glass of a greenhouse and increase
      atmospheric temperature. Even though global warming strongly affects the life of
      the human being, the cause of global warming is still controversial. This work
      thus proposes a fundamental and systematical unsteady one-dimensional heat
      conduction-radiation model together with exponential wide band model to predict
      absorption coefficients affected by concentration, temperature, optical path
      lengths and radiation correlated parameters in different bands centered at 15,
      4.3, 2.7, and 2 MUm of carbon dioxide across the troposphere layer. It shows that
      absorption coefficient required for calculating heat transfer is strongly
      affected by carbon dioxide concentration and optical path length across the
      troposphere. Relevant values of the latter should be greater than 5,000 m.
      Absorption coefficients in the band centered at 4.3 MUm subject to a chosen
      optical path length of 104 m increase from 0.04 m-1 and 0.165 m-1at the
      tropopause to 0.11 m-1 and 0.44 m-1 at the Earth's surface for carbon dioxide
      concentrations of 100 and 400 ppm, respectively. A more relevant and detailed
      temperature profile across the troposphere is presented.

PMID- 30302407
TI  - Endovascular Repair of Bilateral Carotid Dissection in a Near Hanging Victim.
AB  - Introduction: There is much debate in the literature regarding the management of
      blunt cervical carotid injuries. This report describes a case of bilateral
      carotid artery dissection in the very uncommon case of a near hanging victim and
      the treatment controversies regarding its management. Report: A 50 year old male
      patient was admitted after attempted suicide through hanging, having been swiftly
      rescued by a bystander. On admission, six hours after the event there was no
      neurological deficit. There was evidence of soft tissue damage related to the
      rope position, subcutaneous emphysema, and neck swelling. The CT angiogram showed
      dissection of both common carotid arteries with significant luminal narrowing as
      well as fracture of the thyroid cartilage; brain injury was excluded. Heparin
      infusion was started and an endovascular repair with bilateral covered stent
      placement, requiring coverage of the external carotid artery on the left side,
      was performed. The vascular procedure was uneventful. The patient was discharged
      36 days after the event, on dual antiplatelet drugs and under regular psychiatric
      and speech therapy care, and is currently alive and well 22 months after surgery
      with no neurological damage. Discussion: The choice of treatment was not
      straightforward as there are no guidelines or consensus around its management. In
      this case, however, an endovascular repair seemed suitable and the result was
      optimal, with no neurological damage and a good result after 22 months.

PMID- 30302409
TI  - Aldosterone exerts anti-inflammatory effects on LPS stimulated microglia.
AB  - Over the last years, studies on microglia cell function in chronic neuro
      inflammation and neuronal necrosis pointed towards an eminent role of these cells
      in Multiple Sclerosis, Parkinson's and Alzheimer's Disease. It was found, that
      microglia cell activity can be stimulated towards a pro- or an anti-inflammatory
      profile, depending on the stimulating signals. Therefore, investigation of
      receptors expressed by microglia cells and ligands influencing their activation
      state is of eminent interest. A receptor found to be expressed by microglia cells
      is the mineralocorticoid receptor. One of its ligands is Aldosterone, a naturally
      produced steroid hormone of the adrenal cortex, which mainly induces homeostatic
      and renal effects. We evaluated if the addition of Aldosterone to LPS stimulated
      microglia cells changes their inflammatory profile. Therefore, we assessed the
      levels of nitric oxide (NO), iNOS, IL-6, IL-1beta, TNF-alpha and COX-2 in
      untreated, LPS-treated and LPS/Aldosterone-treated microglia cells. Furthermore
      we analyzed p38-MAP-Kinase and NFkappaB signaling within these cells. Our results
      indicate that the co-stimulation with Aldosterone leads to a decrease of the LPS
      induced pro-inflammatory effect and thus renders Aldosterone an anti-inflammatory
      agent in our model system.

PMID- 30302411
TI  - Lifespan reduction due to neoplasia is nullified by pseudoexfoliation syndrome.
AB  - Background: Pseudoexfoliation syndrome (PES) is a common eye condition,
      indicating a risk of various eye diseases. Whether or not PES has extra-ocular
      physiological or even pathophysiological implications has been a matter of
      controversy for years. Methods: In total 1888 persons were examined for PES in
      1985-86. Of these, 1864 (98.7%) had died and were therefore available for
      analysis by 01.01.2016. Age and cause(s) of death were recorded. 9 diagnostic
      groups (cardiovascular disease, cerebrovascular disease, neoplasms, systemic
      hypertension, diabetes mellitus (DM), chronic obstructive pulmonary disease
      (COPD), Parkinson's disease, aortic aneurysm (AA), and amyloidosis) based on ICD
      coding were analyzed for both a possible association between PES and lifespan, as
      well as PES and specific systemic diseases. Findings: In the cardiovascular
      group, PES was not associated with an alteration in longevity. The subgroups
      acute myocardial infarction and other cardiovascular diseases revealed
      significantly reduced and increased lifespan, respectively, compared to the rest
      of the population. These deviations were independent of PES. The impact of PES on
      the neoplasm group showed that PES-positive persons lived 1.81 years (p < 0.001)
      longer than PES-negative persons. No significant differences in the PES
      prevalence were found in any of the cause of death diagnostic groups.
      Interpretations: The present study suggests that lifespan reduction due to
      neoplasia is nullified by PES, and that this phenomenon is not restricted to one
      specific neoplasm type. Thus, the paradoxical conclusion emerges that PES
      provides a lifespan benefit to the patient with a neoplasm. For the remaining
      diagnostic groups, PES was neither associated with an altered lifespan, nor with
      any cause of death diagnoses.

PMID- 30302412
TI  - Fruit characteristics, phytochemical and antioxidant properties of blueberry ash
      (Elaeocarpus reticulatus).
AB  - Blueberry ash (Elaeocarpus reticulatus Sm.) fruit has potential for human
      nutrition, but there is limited information on this fruit. This preliminary study
      aimed to characterise blueberry ash fruit and examine the influence of extraction
      solvents on its phytochemical and antioxidant properties. Blueberry ash fruit is
      dark blue in colour and is a stone fruit of small size (7 mm) and light weight
      (0.2 g). However, it has a high portion of flesh (60% of fruit weight), which is
      edible and can be a potential source of phytochemicals. Water, ethanol,
      acetonitrile, acetone, and their combination were tested for extraction of
      phytochemicals from flesh of this fruit. Water or absolute organic solvent was
      ineffective for extraction of phenolic compounds from this fruit, but mixtures of
      water and organic solvents were more effective, and 50% acetone was the most
      suitable extraction solvent. Extraction with 50% acetone, this fruit was found to
      contain high levels of total phenolic content, flavonoids, proanthocyanidins, and
      anthocyanins (104 mg GAE/g, 155 mg RUE/g, 78 mg CE/g, and 119 mg CGE/g,
      respectively). In addition, this fruit was found to possess potent antioxidant
      properties. Therefore, this fruit should be further studied for identification of
      its phenolic compounds and further tested for their biological properties.

PMID- 30302410
TI  - Xanthine scaffold: scope and potential in drug development.
AB  - Medicinal plants have been the basis for discovery of various important marketed
      drugs. Xanthine is one such lead molecule. Xanthines in various forms (caffeine,
      theophylline, theobromine, etc) are abode in tea, coffee, cocoa, chocolate etc.
      giving them popular recognition. These compounds are best known for their diverse
      pharmaceutical applications as cyclic nucleotide phosphodiesterase inhibition,
      antagonization of adenosine receptor, anti-inflammatory, anti-microbial, anti
      oxidant and anti-tumor activities. These properties incentivize to use xanthine
      as scaffold to develop new derivatives. Chemical synthesis contributes greater
      diversity in xanthine based derivatisation. With highlighting the existing
      challenges in chemical synthesis, the present review focuses the probable
      solution to fill existing lacuna. The review summarizes the available knowledge
      of xanthine based drugs development along with exploring new xanthine led
      chemical synthesis path for bringing diversification in xanthine based research.
      The main objective of this review is to explore the immense potential of xanthine
      as scaffold in drug development.

PMID- 30302413
TI  - Cost and effectiveness of water, sanitation and hygiene promotion intervention in
      Ghana: the case of four communities in the Brong Ahafo region.
AB  - Knowledge of cost and effectiveness of Ghana's main hygiene promotion
      intervention (HPI), Community-Led Total Sanitation (CLTS), is critical for policy
      direction. Cost and resultant effect of HPI is examined using a case study of
      four communities. Surveys were conducted with 300 households, CLTS implementers
      and relevant agencies during the study period (May 2012 to February 2014). The
      HPI produced marginal but statistically significant effect (8%, p < 0.001).
      Improvement in hygiene behaviour was statistically associated with both
      government investments (p < 0.001) and household investments (p < 0.001). Actual
      HPI cost is US$ 90 per household: US$ 51 and 39 from government and households
      respectively. Cost-effectiveness of the HPI is US$ 106.42 per capita of improved
      hygiene behaviour.

PMID- 30302414
TI  - Behavioural flexibility of children with Autism Spectrum Disorder on a card
      sorting task with varying task difficulty.
AB  - Inflexibility is taken to be a key characteristic of Autism Spectrum Disorder
      (ASD), although it is unclear which aspect of cognitive functioning is critical
      in this context. The current study investigated task-switching problems and
      inflexibility with a group of children with ASD, and a mental-aged matched
      control group. Participants (n = 50; mean age = 7 years) completed two card
      sorting tasks, which involved learning to sort by either two or three possible
      dimensions, and then the sorting rule was switched although the number of
      dimensions required to sort the cards remained the same. Following the sorting
      rule change, the ASD group made more errors compared to controls. Errors were
      also related to task type (two or three dimensions), but this was not found to
      interact with ASD. If poor performance were solely dependent on executive
      function (working memory) problems in ASD, then a steeper decrease in performance
      with an increase in task difficulty for one group, compared to another group,
      would be expected. The current results suggest that task difficulty is an aspect
      of importance in set-shifting, but shifting is not differentially affected by
      this component.

PMID- 30302415
TI  - Energy utilization in cattle with steady state and non-steady state methods: the
      importance of thermal neutrality.
AB  - The efficiency by which animals utilize dietary energy is fundamental to the cost
      of production for protein of animal origin and to the carbon footprint an animal
      industry has. Hence, the development of cost effective methodology for
      determining these measurements of efficiency is important. The objective of the
      present study was to investigate the use of infrared thermography in a rapid, non
      steady state method for measuring energy loss in cattle. Data from 241 yearling
      bulls and steers as well as heifers and mature cows are presented. Infrared
      images were collected following a 24h feed withdrawal period. The infrared
      thermal response in these animals was significantly ranked (P < 0.03) with
      conventional measurements of feed efficiency using residual feed intake values
      for animals demonstrated to be within a thermal neutral zone. When animals were
      not within a thermal neutral zone there was no significant ranking. The data
      suggests that the use of a non-steady state approach using infrared thermography
      for identifying metabolic efficiency in animals may be a more rapid and less
      expensive method for identifying differences in energy utilization. The data also
      demonstrates the importance of maintaining thermal neutrality when measuring
      metabolic efficiency irrespective of the methodology.

PMID- 30302416
TI  - The rationale, design, and methods of a randomized, controlled trial to evaluate
      the efficacy of single-dose dexamethasone in reducing post-embolization syndrome
      in patients undergoing uterine artery embolization.
AB  - Background: Uterine artery embolization (UAE) is a minimally invasive technique
      well established for treating symptomatic uterine fibroids. However, the post
      procedure recovery for UAE involves a notable inflammatory process in response to
      ischemia known as post-embolization syndrome (PES). PES encompasses transient
      leukocytosis, low-grade fever, and can result in readmission of up to 10% of
      patients. In surgical settings, multiple studies have demonstrated the efficacy
      of glucocorticoids in reducing inflammation and associated pain. However, this
      approach has not yet been assessed in predominantly ischemia-driven PES. Methods:
      This paper describes the protocol of a prospective randomized, double-blind,
      placebo-controlled, multi-center trial to test the efficacy and safety of single
      dose dexamethasone on inflammatory responses, pain, nausea, and readmission rates
      after UAE. The study will enroll pre-menopausal patients between 25 and 55 years
      (planned enrollment, n = 60) with MRI confirmed symptomatic fibroids. Patients
      will be randomly allocated into two groups: single-dose intravenous dexamethasone
      plus standard of care or placebo (normal saline) plus standard of care. Results:
      The primary endpoint is the patient pain score 4 h following the UAE procedure.
      Secondary endpoints include pain scores at 7 h and 24 h following UAE; narcotic
      usage in the first 24 h following UAE; and serum inflammatory markers (white
      blood cell count, C-reactive protein [CRP], interleukin-6 [IL-6], and cortisol)
      24 h after UAE. Conclusion: Given the high incidence of post-procedure pain and
      difficulty with pain control after uterine artery embolization, results of this
      trial may directly influence the standard of care in perioperative management of
      patients undergoing UAE.

PMID- 30302417
TI  - Reconsideration of sample size and power calculation for overall survival in
      cancer clinical trials.
AB  - When designing a cancer clinical trial, it is usual to assume an exponential
      distribution for a time-to-event outcome such as overall survival (OS). OS is
      often expressed as the sum of progression-free survival (PFS) and survival post
      progression (SPP), each of which is assumed to be exponentially distributed.
      Then, OS does not follow an exponential distribution any more but a gamma or hypo
      exponential distribution. In this study, we derived a sample size calculation
      formula for comparing OS between two treatment arms using the log-rank test for
      OS following a gamma or hypo-exponential distribution. We conducted a simulation
      study to evaluate the sample size and power calculation based on the gamma or
      hypo-exponential distribution. We found that we could reduce the sample sizes
      considerably compared to when assuming an exponential distribution for OS.

PMID- 30302418
TI  - Case series: Use of stromal lenticule as patch graft.
AB  - Purpose: To introduce cases of the use, as patch grafts, of stromal lenticules
      obtained by small incision lenticule extraction (SMILE) surgery. Observations:
      Case 1 was a 79-year-old man who presented with Ahmed-valve-tube exposure in his
      left eye. His uncorrected visual acuity (UCVA) was 20/40, best-corrected visual
      acuity (BCVA) 20/32, and intraocular pressure (IOP) 11 mmHg. He was treated with
      stromal lenticule patch that had been extracted by SMILE surgery. The patch was
      positioned underneath of the conjunctiva and sutured to it. At postoperative 8
      months, the graft site was well maintained without Ahmed valve-tube exposure, the
      UCVA was 20/32, BCVA 20/20, and IOP 12 mmHg.Case 2 was a 60-year-old man who
      presented with Ahmed-valve-tube exposure in his right eye. His UCVA was finger
      count (FC) 30 cm, his BCVA 20/125, and his IOP 14 mmHg. He was treated with
      stromal lenticule patch by the same method as employed in case 1. At
      postoperative 10 days, tube re-exposure and displacement of the Ahmed valve
      external plate toward the limbus area occurred due to loosening of the anchoring
      suture. So, we removed the Ahmed valve device, which had been implanted in the
      supero-temporal area, and performed new Ahmed valve implantation, with a stromal
      lenticule flap instead of a partial scleral flap, in the supero-nasal area. As of
      6 months post-reoperation, the patient was stable, with UCVA 20/200, BCVA 20/40
      and IOP 13 mmHg.Case 3 was a 74-year-old man who presented with bullous
      keratopathy in his right eye, which was blind. Due to severe adhesions, his
      conjunctiva could not cover the entire cornea. Therefore, we performed a stromal
      lenticule patch graft with conjunctival advance flap. At postoperative 3 months,
      the patient's right eye was stable, without displacement or melting of the
      lenticule graft. Conclusions & importance: It is suggested that the stromal
      lenticule, with its biocompatibility, sufficient strength, ease of handling and
      low cost, is a useful patch graft for various therapeutic purposes in the
      ophthalmic field.

PMID- 30302419
TI  - Trigeminal hypertrophic interstitial neuropathy presenting as unilateral
      proptosis, ptosis, tearing, and facial neuralgia.
AB  - Purpose: To show the utility of MRI and histology in diagnosing rare cases of
      trigeminal hypertrophic interstitial neuropathy (HIN). Observations: A 57-year
      old African-American woman presented with a 4-year history of right eye proptosis
      with tearing, headaches, and worsening right-sided trigeminal neuralgia symptoms
      and jaw pain. HIV and diabetes tests were negative and thyroid function was
      normal. MRI identified abnormal thickening of all trigeminal nerve divisions and
      proptosis secondary to right trigeminal nerve V1 division enlargement. The
      excised tissue contained S-100 positive Schwann cells in an onion-bulb pattern.
      Headaches resolved, but proptosis and mild trigeminal neuralgia remained 1 year
      post-surgery. Conclusions and importance: Trigeminal HIN is very rare, but
      presents as chronic progressive ocular symptoms with trigeminal neuralgia.
      Trigeminal nerve hypertrophy is identified by MRI and confirmed
      histopathologically by detection of Schwann cells in an onion bulb formation.

PMID- 30302421
TI  - Visualization of Macroprolactinoma by 18F-Fluorocholine PET/CT in a Patient With
      Multiple Endocrine Neoplasia Type 1.

PMID- 30302420
TI  - A Pre-Pregnancy Biomarker Risk Score Improves Prediction of Future Gestational
      Diabetes.
AB  - Context: Previous studies have not examined the ability of multiple preconception
      biomarkers, considered together, to improve prediction of gestational diabetes
      mellitus (GDM). Objective: To develop a preconception biomarker risk score and
      assess its association with subsequent GDM. Design: A nested case-control study
      among a cohort of women with serum collected as part of a health examination
      (1984 to 1996) and subsequent pregnancy (1984 to 2009). Biomarkers associated
      with GDM were dichotomized into high/low risk. Setting: Integrated health care
      system. Participants: Two controls were matched to each GDM case (n = 256 cases)
      on year and age at examination, age at pregnancy, and number of pregnancies
      between examination and index pregnancy. Main Outcome Measure: GDM. Results: High
      risk levels of sex hormone-binding globulin (SHBG; <44.2 nM), glucose (>90
      mg/dL), total adiponectin (<7.2 MUg/mL), and homeostasis model assessment
      estimated insulin resistance (>3.9) were independently associated with 2.34 [95%
      confidence interval (CI): 1.50, 3.63], 2.03 (95% CI: 1.29, 3.19), 1.83 (95% CI:
      1.16, 2.90), and 1.67 (95% CI: 1.07, 2.62) times the odds of GDM and included in
      the biomarker risk score. For each unit increase in the biomarker risk score,
      odds of GDM were 1.94 times greater (95% CI: 1.59, 2.36). A biomarker risk score
      including only SHBG and glucose was sufficient to improve prediction beyond
      established risk factors (age, race/ethnicity, body mass index, family history of
      diabetes, previous GDM; area under the curve = 0.73 vs 0.67, P = 0.002).
      Conclusions: The improved, predictive ability of the biomarker risk score beyond
      established risk factors suggests clinical use of the biomarker risk score in
      identifying women at risk for GDM before conception for targeted prevention
      strategies.

PMID- 30302422
TI  - Experimental BPA Exposure and Glucose-Stimulated Insulin Response in Adult Men
      and Women.
AB  - Context: Human cross-sectional and animal studies have shown an association of
      the chemical bisphenol A (BPA) with insulin resistance, type 2 diabetes, and
      other metabolic diseases, but no human experimental study has investigated
      whether BPA alters insulin/C-peptide secretion. Design: Men and postmenopausal
      women (without diabetes) were orally administered either the vehicle or a BPA
      dose of 50 ug/kg body weight, which has been predicted by US regulators (Food and
      Drug Administration, Environmental Protection Agency) to be the maximum, safe
      daily oral BPA dose over the lifetime. Insulin response was assessed in two cross
      over experiments using an oral glucose tolerance test (OGTT; experiment 1) and a
      hyperglycemic (HG) clamp (experiment 2). Main outcomes were the percentage change
      of BPA session measures relative to those of the control session. Results: Serum
      bioactive BPA after experimental exposure was at levels detected in human
      biomonitoring studies. In the OGTT, a strong positive correlation was found
      between hemoglobin A1c(HbA1c) and the percentage change in the insulinogenic
      index (Spearman = 0.92), an indicator of early-phase insulin response, and the
      equivalent C-peptide index (Pearson = 0.97). In the HG clamp study, focusing on
      the later-phase insulin response to a stable level of glucose, several measures
      of insulin and C-peptide appeared suppressed during the BPA session relative to
      the control session; the change in insulin maximum concentration (Cmax) was
      negatively correlated with HbA1c and the Cmax of bioactive serum BPA.
      Conclusions: This exploratory study suggests that BPA exposure to a dose
      considered safe by US regulators may alter glucose-stimulated insulin response in
      humans.

PMID- 30302424
TI  - Early-Onset Diabetes Mellitus in a Patient With a Chromosome 13q34qter
      Microdeletion Including IRS2.
AB  - Diabetes mellitus is a multifactorial disease caused by a complex interaction of
      environmental and genetic factors. Some diabetes mellitus cases, however, are
      caused by a limited number of mutant genes. Chromosome 13q deletion syndrome, an
      extremely rare genetic disorder, is caused by structural and functional monosomy
      of the 13q chromosomal region. We report the case of a 38-year-old Japanese man
      with Chr13q deletion (a mosaic pattern with heterozygous ring Chr13q) who
      developed diabetes mellitus. Early-onset diabetes mellitus developed in this
      patient because of insulin resistance and a lack of adequate insulin secretion.
      Microarray analysis identified a 4.8-Mb deletion of distal Chr13q, leading to a
      copy number loss of 40 genes. Among those genes, the insulin receptor substrate 2
      gene (IRS2) was the most likely causative candidate for the development of
      diabetes mellitus in this patient, based on the model of IRS2 knockout mice,
      which have abnormal glucose and insulin homeostasis closely resembling the human
      diabetes phenotype. These data provide important information regarding the
      contribution of a microdeletion of Chr13q, including in IRS2, to the pathogenesis
      of diabetes mellitus in humans.

PMID- 30302425
TI  - Experimental pericardial tamponade-translation of a clinical problem to its large
      animal model.
AB  - Objectives: Pericardial tamponade is a life-threatening medical emergency, when
      the hemodynamic consequences of low cardiac output severely disturb the perfusion
      of the peripheral tissues. Our aim was to design a reliable large animal model to
      reproduce the clinical scenario with the relevant pathophysiological consequences
      of pericardial tamponade -induced cardiogenic shock. Material and Methods:
      Anesthetized Vietnamese mini pigs were used (n=12). Following laparotomy, a
      cannula was fixed into the pericardium through the diaphragm without thoracotomy.
      A sham-operated group (n=6) served as control, while in the second group (n=6)
      pericardial tamponade was induced by intra-pericardial injection of heparinized
      own blood. Throughout the 60-min pericardial tamponade and the 180-min
      reperfusion, macro hemodynamics, renal circulation and the mesenteric macro- and
      micro-circulatory parameters were monitored. Myeloperoxidase activity was
      measured to detect neutrophil leukocyte accumulation and in vivo histology was
      performed by confocal laser scanning endomicroscopy to observe the structural
      changes of the intestinal mucosa. Results: PT increased the central venous
      pressure, heart rate, and decreased mean arterial pressure. The mesenteric artery
      flow (from 355.5+/-112.4 vs 182.0+/-59.1 mL/min) and renal arterial flow (from
      159.63+/-50.7 vs 35.902+/-27.9 mL//min) and the micro-circulation of the ileum
      was reduced. The myeloperoxidase activity was elevated (from 3.66+/-1.6 to 7.01+/
      1.44 mU/mg protein) and manifest injury of the ileal mucosa was present.
      Conclusion: This experimental model suitably mimics the hemodynamics and the
      pathology of clinical pericardial tamponade situations, and on this basis, it
      provides an opportunity to study the adverse macro- and micro-circulatory effects
      and biochemical consequences of human cardiogenic shock.

PMID- 30302423
TI  - Current Understanding of the Role of Nesfatin-1.
AB  - Nesfatin-1 was discovered in 2006 and implicated in the regulation of food
      intake. Subsequently, its widespread central and peripheral distribution gave
      rise to additional effects. Indeed, a multitude of actions were described,
      including modulation of gastrointestinal functions, glucose and lipid metabolism,
      thermogenesis, mediation of anxiety and depression, as well as cardiovascular and
      reproductive functions. Recent years have witnessed a great increase in our
      knowledge of these effects and their underlying mechanisms, which will be
      discussed in the present review. Lastly, gaps in knowledge will be highlighted to
      foster further studies.

PMID- 30302426
TI  - The role of co-administration of damage control surgery and vacuum-assisted
      closure in the treatment of perineal wounds.
AB  - Perineal wounds caused by high-kinetic-energy shotgun blasts have a high
      mortality risk because they are often accompanied by injuries of the anus,
      rectum, genitourinary system, and extremities. Mortality often results from
      hemorrhage in the early stage and from multiple organ failure caused by sepsis in
      the late stage. The primary step in the treatment of patients presenting with
      perineal wound and hemodynamic instability caused by severe hemorrhage is to
      control hemorrhage and contamination using damage control surgery. After
      achieving hemodynamic stability, vacuum-assisted closure can be used to reduce
      the risks of infection and sepsis. In this report, we present a case who had a
      perineal wound caused by a mine blast and was successfully treated by damage
      control surgery and vacuum-assisted closure.

PMID- 30302427
TI  - Pancreatic extragastrointestinal stromal tumor invading the duodenum.
AB  - Extragastrointestinal stromal tumors that arise in the pancreas are extremely
      rare and managing them can be difficult, particularly if located in the head of
      pancreas. This case report aims to contribute to the existing data in the
      literature regarding extragastrointestinal stromal tumors with rare and unusual
      locations. We present a 56-year-old man who presented with recurrent mild right
      upper quadrant abdominal pain. Abdominal computed tomography and magnetic
      resonance imaging revealed a mass lesion with a diameter of 10 cm localized in
      the head of pancreas. Pancreaticoduodenectomy with complete tumor excision was
      performed. He was discharged on the postoperative day 14. Only 15
      extragastrointestinal stromal tumors cases have been reported. Of these 15 cases,
      tumors were located in the head of pancreas in six cases. Here we report the
      seventh case of pancreatic extragastrointestinal stromal tumor arising in the
      head of pancreas and also the largest of these seven tumors.

PMID- 30302428
TI  - Goblet cell carcinoid of the appendix accompanied by adenomatous polyp with high
      grade dysplasia at the cecum.
AB  - Goblet cell carcinoid tumor of the appendix is an uncommon neoplasia that shares
      the histological attributes of both adenocarcinoma and carcinoid tumors. Its
      prognosis has a more aggressive course than the other known carcinoid tumors.
      Clinical diagnosis of goblet cell carcinoid is seldom made preoperatively. The
      most common clinical presentation of goblet cell carcinoid tumor is acute
      appendicitis. In this study, we report a patient on whom right hemicolectomy was
      performed because of a cacal sessile polyp with high grade dysplasia; goblet cell
      carcinoid tumor of the appendix was revealed incidentally during microscopic
      evaluation of the appendectomy specimen. The patient healed uneventfully and no
      recurrence was observed after the 12-month follow-up period. Careful microscopic
      examination of the appendectomy specimen is key for the diagnosis of appendiceal
      tumors such as goblet cell carcinoid, especially in elderly patients.

PMID- 30302429
TI  - Cutaneous metastasis of colon adenocarcinoma.
AB  - Skin metastasis originating from colorectal cancer is a rare entity and usually
      signifies poor prognosis. We present a case of a 62-year-old male patient who
      presented with a cutaneous metastatic focus on his forehead after five years of
      the primary treatment of colon cancer. Complete response from the cutaneous
      metastasis nodule was achieved with radiotherapy. The patient is still alive and
      under a second-line palliative chemotherapy regimen because of the multiple liver
      metastases. It is important for physicians to be aware of skin metastasis in
      patients with an oncology history.

PMID- 30302430
TI  - Symptomatic hepatic metastasis of insulinoma 15 years after pancreatic resection.
AB  - Malignant insulinomas are infrequent endocrine tumors with miscellaneous clinical
      courses. In this report, we present a rare case of insulinoma that recurred with
      solitary hepatic metastasis 15 years after the initial resection of the primary
      tumor from the pancreas. A 20-year-old woman first presented with the symptoms of
      hypoglycemia in 1996. The diagnosis of pancreatic insulinoma was confirmed by
      laboratory findings, and the initial surgery had been performed involving
      complete enucleation of the pancreatic mass. Histopathologically, the tumor was
      diagnosed as a benign adenoma. After 15 years, the patient experienced symptoms
      of hypoglycemia again, and laboratory findings and abdominal computed tomography
      identified a lesion in the liver. Intraoperative ultrasound did not show any
      lesion in the pancreas, and wedge resection was performed for the hepatic lesion.
      Postoperative blood glucose levels returned to normal. Histopathologic
      examination confirmed the diagnosis of liver metastasis of a neuroendocrine
      tumor. This is the longest interval between primary tumor and the metastasis
      reported in the literature, for insulinoma. Thus, it should be remembered that
      long-term follow-up is mandatory for the patients with insulinoma even after
      resection of the primary tumor. Resection is recommended when a metastatic lesion
      is observed.

PMID- 30302431
TI  - A case report of left paraduodenal hernia diagnosed preoperatively and treated
      laparoscopically.
AB  - Paraduodenal hernia is a rare congenital anomaly; however, it is the most common
      cause of internal herniation. Clinical findings are often indeterminate.
      Computerized tomography is usually diagnostic; however, the diagnosis is often
      made intra-operatively. Paraduodenal hernia carries a risk of incarceration
      leading to bowel obstruction and strangulation; therefore, it should be repaired
      surgically when diagnosed. Here we present a case of left PDH that was diagnosed
      preoperatively and repaired laparoscopically.

PMID- 30302432
TI  - Transcervical resection of two parathyroid adenomas located on the anterior
      mediastinum.
AB  - The mediastinum is a possible location of ectopic parathyroid adenoma. Most
      ectopic parathyroid glands in the mediastinum are found in the superior
      mediastinum within the thymus. In this article, two cases with ectopic
      mediastinal parathyroid adenomas that were excised via transcervical resection
      are presented. Preoperative examination of the two cases was performed.
      Laboratory tests supported hyperparathyroidism. For both patients, the results of
      radiologic and scintigraphic examinations of the cases were compatible with
      parathyroid adenoma masses in the anterior mediastinum. Transcervical resection
      was performed via suprasternal incision through the sternal notch and the
      posterior wall of the sternum space by blunt dissection with the finger. The soft
      lesions were removed en bloc in both cases. The parathyroid hormone levels of the
      two cases decreased dramatically after the operation. Transcervical resection may
      be an alternative method to major surgery in anterior mediastinal small masses.

PMID- 30302433
TI  - Idiopathic renal replacement lipomatosis: A diagnostic and therapeutic challenge.
AB  - Renal replacement lipomatosis is a rare benign renal disorder where the renal
      parenchyma is replaced by mature fatty tissue. It poses a diagnostic challenge to
      the clinicians due to an unusual presentation and clinical features. The disease
      usually presents in middle age with vague pain in the affected flank and variable
      urological symptoms. Although the condition is preceded by calculus disease or
      chronic inflammation, as an extremely rare occurrence, it can occur without any
      pre-existing condition, as in our case. Increasing awareness among the surgeons
      about the existence of such a condition will help the surgical fraternity to
      diagnose and manage such cases properly.

PMID- 30302434
TI  - Perforation of the small intestine caused by enteropathy-associated T cell
      lymphoma.
AB  - Enteropathy-associated T cell lymphoma is a rare lymphoma specific to the
      gastrointestinal system, arising from intraepithelial T lymphocytes, that is
      often associated with celiac disease. We report a 53-year-old female patient with
      no previous disease who presented with severe abdominal pain. Physical
      examination revealed diffuse abdominal tenderness and abdominal guarding and the
      patient underwent emergency surgery with a diagnosis of acute abdomen. During the
      operation, a 20-cm mass was found located on Treitz ligament, invading the
      duodenum and pancreatic head and perforating the jejunum. Histologically, medium
      sized monomorphic atypical lymphocyte infiltration with dark nucleus and narrow
      cytoplasm was seen in the layers of mucosa, submucosa, muscular wall, and serosa
      of the duodenum. The final pathological diagnosis was "enteropathy-associated T
      cell lymphoma type 2" based on immunohistochemical and serological findings.
      Based on the World Health Organization 2008 criteria, enteropathy-associated T
      cell lymphoma has two subtypes. Type 1 enteropathy-associated T cell lymphoma is
      associated with celiac disease and has HLA DQ2 and HLA DQ8 genotype. Enteropathy
      associated T cell lymphoma 2 enteropathy-associated T cell lymphoma seldom occurs
      and is not associated with celiac disease.

PMID- 30302436
TI  - Editorial: How digital are you?

PMID- 30302435
TI  - Foreign body: A sewing needle migrating from the gastrointestinal tract to
      pancreas.
AB  - Of all ingested foreign bodies, 2.4% comprise of sewing needles. Through
      perforation of gastrointestinal tract, which occurs in 1% of cases, they can
      migrate into the liver and pancreas. Foreign bodies in pancreas should be
      considered in the differential diagnosis of chronic abdominal pain. Computed
      tomography scans provide valuable information for the localization of the lesion,
      which guide the surgeon during the operation. Secondary to foreign bodies that
      migrate to the pancreas, complications with high mortality such as pancreatitis,
      pseudoaneurysm, and pancreas abscess can be seen. Thus, for this patient group,
      diagnostic laparoscopy is recommended, considering its advantages of decreased
      postoperative pain, decreased wound infection, and faster recovery time. Here we
      present a case of a 23-year-old female patient, from whom an ingested needle that
      migrated from the back wall of the stomach to the pancreas was extracted by
      laparoscopic surgery.

PMID- 30302437
TI  - The full-mouth mock-up: a dynamic diagnostic approach (DDA) to test function and
      esthetics in complex rehabilitations with increased vertical dimension of
      occlusion.
AB  - The mock-up is a diagnostic technique that allows for the intraoral try-in of a
      prosthetic rehabilitation. Mock-ups facilitate significant improvement in
      communication with patients by showing them the potential final outcome of the
      treatment. They also allow for a quick and easy comparison of the pre- and
      postoperative situations, and permit the clinician to check the functional
      aspects of the therapy. The purpose of this article is to describe the use of the
      full-mouth mock-up technique for testing all the functional and esthetic
      parameters of extensive rehabilitations associated with a VDO increase with
      completely additive wax-ups. The proposed clinical procedures describe an easy
      and reversible technique to manage complex prosthetic cases with a more
      conservative and operator-friendly approach compared with conventional prosthetic
      therapies, reducing time and costs. All the clinical and technical phases of this
      approach are described step by step.

PMID- 30302438
TI  - A patient-calibrated individual wax-up as an essential tool for planning and
      creating a patient-oriented treatment concept for pathological tooth wear.
AB  - Tooth wear is generally a physiological process; however, it can also be a
      pathological condition associated with attrition, abrasion, and erosion processes
      in which the quantity of tooth loss is atypical for the patient's age. Tooth
      substance loss often causes functional problems, symptoms of discomfort/pain, and
      esthetic impairments. Patients presenting this condition frequently need
      restorative treatment, combined with an increase in the vertical dimension of
      occlusion (VDO). A diagnostic wax-up (DWU) provides assistance in determining a
      new occlusal plane and VDO, and is a fundamental tool considering the backward
      planning involved in the execution of a complex rehabilitation. In cases of
      severe tooth wear, preventive measures must be taken. Yet, when a restorative
      intervention is needed, the use of a DWU, in conjunction with a mock-up, helps to
      achieve a predictable and satisfactory outcome. This article presents a case
      report of a young female patient with pathological tooth wear, related
      symptomatology, and esthetic complaints. Initially, a DWU and a diagnostic mock
      up were created. After esthetic and functional corrections, a second DWU was
      generated and transferred to the patient's mouth by means of a therapeutic mock
      up. This mock-up was used as a trial restoration for the pretreatment phase, to
      evaluate the new VDO/esthetics/function and to guide tooth preparation. Lithium
      disilicate (LS2) occlusal onlays were used to stabilize the VDO, and anterior LS2
      and feldspathic veneers, combined with direct composite restorations, were
      executed to reach the planned minimally invasive result.

PMID- 30302439
TI  - Details of pleasing smiles.
AB  - PURPOSE: To determine the most and least attractive smiles from a Brazilian
      sample and to correlate the anatomical characteristics identified in these
      smiles. MATERIALS AND METHODS: Orthodontists, dentists, and laypeople assessed
      the photographs of 86 students (66 women and 20 men), aged between 19 and 30
      years, using a visual analog scale (VAS). An evaluator blinded to the results
      measured the esthetic composition of the eight photographs with the highest and
      the eight with the lowest ratings for women, and the two with the highest and the
      two with the lowest ratings for men. The mean and standard deviations were
      calculated for the descriptive analysis. RESULTS: A total of 42 anatomical smile
      details were identified and described, obtaining the means of the
      characteristics. CONCLUSIONS: The following characteristics were observed from
      the selected most attractive smiles: parallel smile arc, oval-shaped incisors
      with square-rounded edges, increase of the incisal embrasure and reduction of
      connector space in distal progression, display of maxillary incisors and minimum
      display of mandibular teeth, gingival margin of central incisors 0.5 mm coronal
      to the canines and 0.8 mm apical to the lateral incisors, posterior gingival
      display of 1.5 mm, less than 20% of buccal corridor and display of 12 teeth, and
      canines with -2 degrees of inclination. The most attractive smiles also had an
      absence of asymmetries, diastemas, black spaces, incisal plane inclination, and
      anterior gingival display.

PMID- 30302440
TI  - Update on the 'index technique' in worn dentition: a no-prep restorative approach
      with a digital workflow.
AB  - Following the guidelines of the 'index technique' that were published in this
      journal in 2015, this article presents the 'digital index technique,' an updated
      no-prep restorative approach to the management of worn dentition. Patients with
      minimal, moderate, and severe hard tissue wear can be treated based on the
      application of minimally invasive or noninvasive adhesive composite restorations
      on posterior and anterior worn dentition. The technique allows for a purely
      additive treatment without sacrificing healthy hard tooth tissue. It follows the
      principles of biodentistry (maximum conservation of healthy tissue), and the
      reinforcing of residual dental structure. Depending on the severity of the enamel
      and dentin wear, the number of caries, and the size of the existing restorations,
      different treatment options can be applied to each tooth: direct and indirect
      partial restorations or full crowns. It is essential to diagnose and treat tooth
      surface loss in order to properly restore biomechanics, function, and esthetics
      by means of adhesive restorations. This article proposes that the update of the
      index technique through the digital workflow is a fast and conservative approach
      for the planning and management of a full-mouth adhesive restoration in all cases
      of light, moderate, and severe worn dentition. The technique is based on a 'copy
      and-paste' guided approach, stamping composite resin directly onto the tooth
      surface by means of a transparent index created from a full-mouth digital
      restorative wax-up, following an initially planned increase in occlusal vertical
      dimension (OVD) through an esthetic and functional analysis.

PMID- 30302441
TI  - Double-layer build-up technique: laser evaluation of light propagation in dental
      substrates and dental composites.
AB  - PURPOSE: To evaluate and compare light propagation in dental tissues and dental
      composite restorations using a double-layer build-up technique. MATERIALS AND
      METHODS: Natural teeth slabs and dental restoration buildups with A2D and B1E
      colored nanofilled, supra-nanofilled, and microhybrid composites were randomized
      and equally distributed into four experimental groups (n = 10). Using a
      spectrophotometer, the samples were irradiated by three wavelengths of lasers:
      red, green, and blue. A voltmeter recorded the light output signal, and the
      following optical constants were calculated: absorption (A), transmittance (T),
      and attenuation (K). The data were analyzed using one-way analysis of variance
      (ANOVA), followed by post hoc Tukey's test (alpha = 0.05). RESULTS: Absorption
      results varied according to the laser color and different composites tested.
      Regardless of the laser wavelength, the supra-nanofilled composite showed greater
      light transmittance and lower light attenuation compared with the dental tissues,
      which was the opposite of the nanofilled composite. The microhybrid composite
      showed no difference in light transmittance or light attenuation compared with
      the dental tissues. CONCLUSION: Within the limitations of this observational in
      vitro study, the microhybrid dental composite group had the most similar light
      propagation pattern compared with natural teeth when using the double-layer build
      up technique.

PMID- 30302442
TI  - Accuracy of computerized and conventional impression-making procedures for
      multiple straight and tilted dental implants.
AB  - PURPOSE: To compare the accuracy of implant impressions using computer-aided
      impression-making technology and a conventional approach in a standardized
      setting in vitro, and to verify the effect of implant angulation (40 to 45
      degrees) on the accuracy of digital and conventional impression-making
      procedures. MATERIALS AND METHODS: Four different edentulous mandibular reference
      models (RMs) were manufactured. Two straight (RM1); four straight (RM2); two
      straight and two tilted (RM3); and six straight (RM4) dental implants were
      placed, simulating four different clinical scenarios. The computer-aided
      impressions (n = 5 for each RM) were made using an intraoral scanner (IOS) (True
      Definition, 3M ESPE). Polyether (n = 5 for each RM) and vinyl polysiloxane (n = 5
      for each RM) impression materials were utilized for the conventional approach.
      The collected data were analyzed in terms of trueness. The statistical analysis
      was performed using one-way analysis of variance (ANOVA). RESULTS: The overall
      differences of interimplant distance, identified in mean values, were
      statistically significant among the different impression-making groups in RM1,
      RM3, and RM4. The data analyses of overall interimplant angle deviations yielded
      statistically significant differences in all four RMs. However, the deviations
      obtained with both impression-making approaches did not exceed an interimplant
      distance threshold of 100 um, and an interimplant angle of 0.5 degrees, which
      seems to be clinically acceptable. CONCLUSION: Within the limits of this in vitro
      study, the accuracy of the computer-aided and conventional impression-making
      approaches for straight and tilted dental implants was comparable, and might be
      clinically considered for full-arch, multiple-implant restorations. However,
      further clinical studies are required to verify the feasibility of different IOSs
      (with and without scanning powder application), different implant systems, and
      multiple implant configurations.

PMID- 30302443
TI  - Topochemical synthesis of 2D materials.
AB  - Since the demonstration of the unique properties of single-layer graphene and
      transition metal dichalcogenides (TMDs), research on two-dimensional (2D)
      materials has become one of the hottest topics, with the family of 2D materials
      quickly expanding. This expansion is mainly attributable to the development of
      new synthesis methods to create new materials. This review will summarize and
      critically analyze topochemical synthesis methods for synthesizing novel 2D
      materials. For example, the emerging family of 2D transition metal carbides,
      nitrides and carbonitrides (MXenes) are synthesized primarily by selective
      etching of "A" (metal) elements from MAX phases. Another 2D material,
      hydrogenated germanene is produced by selective etching of calcium digermanide
      (CaGe2). The topochemical transformation of one dichalcogenide into another and
      2D oxides into 2D carbides or nitrides have attracted great attention because
      materials with many useful and diverse properties can be obtained by these
      methods. Topochemical synthesis methods provide alternative ways of synthesizing
      2D materials not requiring van der Waals bonded solid precursors or vapor phase
      deposition, but they have not been comprehensively reviewed. In this review, we
      describe common principles of topochemical synthesis of 2D materials, explain
      synthesis mechanisms and offer an outlook for future research.

PMID- 30302444
TI  - Solvatochromism, acidochromism and aggregation-induced emission of propeller
      shaped spiroborates.
AB  - Propeller-shaped pyridyl-enolato-catecholate/-salicyl spiroborates (Sborepy1-6)
      were synthesized. The complexes Sborepy3-6 show weak emission in fluid solution
      and aggregation-induced emission enhancement in the aggregation state with large
      Stokes shifts of 4025-5237 cm-1. Moreover, intense solid-state emissions with
      high Phif ranging from 25% to 37% were observed for Sborepy3-6 owing to the weak
      intermolecular interactions in their solid-state. The AIE and intense solid-state
      emission have been revealed via the X-ray diffraction analysis and theoretical
      calculations. Furthermore, the solvatochromism in the solution state and the
      potential application as a fluorescent acidic vapour sensor in the solid state of
      Sborepy3 and Sborepy6 were also demonstrated.

PMID- 30302445
TI  - Slow magnetic relaxation in a Tb(iii)-based coordination polymer.
AB  - A Tb(iii)-based coordination polymer (polyTb) was synthesized by complexation of
      Tb(NO3)3.(6H2O) and 4',4''''-[1,1'-biphenyl]-4,4'-diylbis[6,6''
      bis(ethoxycarbonyl)2':6',2''-terpyridine](L). The polymer structure was
      determined by Job's plots, DFT calculation, and X-ray absorption fine structure
      (XAFS) measurement. Job's plots indicated that the mole ratio (Tb ion : L) is 1 :
      1. The optimized model structures suggested a La model: the LaN6(O[double bond,
      length as m-dash]C)2 model. The bond distances of La-O and La-N are ~2.80 A and
      2.60 A, respectively. The EXAFS fitting indicated that the bond distances of Tb-O
      and Tb-N are 2.65 A and 2.95 A, respectively. polyTb shows field-induced magnetic
      relaxation in the solid and solution state. The luminescence of polyTb,
      originating from an f-f transition, was observed (phi = 6.9%). polyTb formed a
      porous structure on a Si substrate, whereas a fibrous complex structure was
      formed on glass. polyTb chains are orientated on glass, which were determined by
      XRD.

PMID- 30302446
TI  - Dimensional tailoring of hydrothermally grown zinc oxide nanostructures in a
      continuous flow micro reactor.
AB  - Dynamic deposition of ZnO nanostructures with varying morphologies (nanorods,
      nanocones, nanopencils, nanosheets, etc.), diameters, lengths and aerial
      densities on ITO-PET substrates has been achieved using a continuous flow
      microreactor in which we maintained a homeostatic zinc concentration and varied
      the other reactants' concentrations.

PMID- 30302447
TI  - An efficient multifunctional hybrid electrocatalyst: Ni2P nanoparticles on MOF
      derived Co,N-doped porous carbon polyhedrons for oxygen reduction and water
      splitting.
AB  - Ni2P nanoparticles anchored on MOF-derived Co,N-doped porous carbon polyhedrons
      (Ni2P/CoN-PCP) were successfully prepared. The Ni2P/CoN-PCP catalyst shows
      excellent trifunctional electrocatalytic performances for the oxygen reduction,
      oxygen evolution, and hydrogen evolution reactions, attributed to the synergistic
      effect between active Ni2P nanoparticles and the CoN-PCP support with rich Co-Nx
      centres, abundant defects and high conductivity. This work demonstrates a
      superior low-cost electrocatalyst for potential application in fuel cells and
      water splitting devices.

PMID- 30302448
TI  - Consecutive one-/two-step relaxation transformations of single-molecule magnets
      via coupling dinuclear dysprosium compounds with chloride bridges.
AB  - The double chloride-bridged dimer of a dinuclear dysprosium(iii) single-molecule
      magnet (SMM) was successfully isolated by assembling centrosymmetric dinuclear
      Dy2 SMMs. Such structural transformation involves the generation and cleavage of
      chloride bridges and leads to consecutive transformations of one- and two-step
      slow relaxation of magnetization.

PMID- 30302449
TI  - From double-shelled grids to supramolecular frameworks.
AB  - Structurally unique double-shelled 4f and 3d-4f supramolecular grids were
      constructed and assembled into 3D hydrogen-bonded organic frameworks (HOFs), with
      the 3d-4f heterometallic HOF showing single-molecule magnet (SMM) behaviour.

PMID- 30302450
TI  - Fully quantum calculation of the second and third virial coefficients of water
      and its isotopologues from ab initio potentials.
AB  - Path-Integral Monte Carlo methods were applied to calculate the second, B(T), and
      the third, C(T), virial coefficients for water. A fully quantum approach and
      state-of-the-art flexible-monomer pair and three-body potentials were used.
      Flexible-monomer potentials allow calculations for any isotopologue; we performed
      calculations for both H2O and D2O. For B(T) of H2O, the quantum effect
      contributes 25% of the value at 300 K and is not entirely negligible even at 1000
      K, in accordance with recent literature findings. The effect of monomer
      flexibility, while not as large as some claims in the literature, is significant
      compared to the experimental uncertainty. It is of opposite sign to the quantum
      effect, smaller in magnitude than the latter below 500 K, and varies from 2% at
      300 K to 10% at 700 K. When monomer flexibility is accounted for, results from
      the CCpol-8sf pair potential are in excellent agreement with the available
      experimental data and provide reliable B(T) values at temperatures outside the
      range of experimental data. The flexible-monomer MB-pol pair potential yields
      B(T) values that are slightly too high compared to experiment. For C(T), our
      calculations confirm earlier findings that the use of three-body potential is
      necessary for meaningful predictions. However, due to various uncertainties of
      the potentials used, especially the three-body ones, we were not able to
      establish benchmark values of C(T), although our results are in qualitative
      agreement with available experimental data. The quantum effect, never before
      included for water, reduces the magnitude of the classical value for H2O by a
      factor of 2.5 at 300 K and is not entirely negligible even at 1000 K.

PMID- 30302451
TI  - Perfectly isoselective polymerization of 2-vinylpyridine promoted by beta
      diketiminato rare-earth metal cationic complexes.
AB  - Symmetric and asymmetric beta-diketiminato rare-earth metal dialkyl complexes
      L1Ln(CH2SiMe3)2(THF) (L1 = (2,6-Et2C6H3)NC(Me)CHC(Me)N(2,6-Et2C6H3), Ln = Y (1a),
      Lu (1b)) and L2Ln(CH2SiMe3)2(THF) (L2 = (2,6-iPr2C6H3)NC(Me)CHC(Me)N(C6H5), Ln =
      Y (2a), Lu (2b)) have been synthesized by the reaction of the precursor
      Ln(CH2SiMe3)3(THF)2 with the corresponding pro-ligands (HL1 and HL2) in good
      yield. These complexes promote the polymerization of 2-vinylpyridine (2-VP) to
      produce isotactic-biased poly(2-vinylpyridine) (P2VP) (mm: 40%) in quantitative
      yield. The in situ generated cationic species with the addition of borate
      ([Ph3C][B(C6F5)4], [PhNHMe2][B(C6F5)4]) prior to the polymerization display
      distinct results, and the symmetric ones afford perfectly isotactic P2VP with an
      mm value up to 99%, whilst the asymmetric ones produce atactic P2VP (mm: 26%).
      The 1H NMR spectrum and MALDI-TOF mass analysis of an oligomer prepared with
      1a/[Ph3C][B(C6F5)4] indicate that the polymerization is initiated by coordination
      insertion of 2-VP into the Y-CH2SiMe3 bond of the in situ generated cationic
      species.

PMID- 30302452
TI  - Rh(iii)-Catalyzed ortho-C-(sp2)-H amidation of ketones and aldehydes under
      synergistic ligand-accelerated catalysis.
AB  - Rh(iii)-Catalyzed ortho-C-H amidation of ketones and aldehydes under cooperative
      metal organocatalysis has been utilized for synthesizing various ortho
      amidocarbonyl analogs, and the reaction for the aldehyde proceeds at ambient
      temperature. The aniline derivative 3,5-bis(trifluoromethyl)aniline promotes the
      amidation reaction via a transient imine directing group. The efficient amidation
      agent is dioxazolone. The synthetic utility has been demonstrated in the
      synthesis of quindolinone alkaloids.

PMID- 30302453
TI  - A new salicylaldehyde-based azo dye and its two lanthanide(iii) complexes
      displaying slow magnetic relaxation.
AB  - A new salicylaldehyde-based azo dye 5-azotriazolyl-3-methoxysalicylaldehyde
      (H2TMSA) and its two Ln3+ complexes
      {[Ln(HTMSA)3(H2O)2][Ln(HTMSA)3(DMF)(H2O)]}.15H2O (Ln = Dy(1) and Tb(2)) have been
      synthesized and characterized by IR, Raman, 1H NMR and single-crystal X-ray
      diffraction techniques. H2TMSA shows an azo form in acidic (pH < 5.05) and strong
      basic (pH > 12.41) conditions, and a pH-dependent azo-hydrazone tautomerism in
      the range of pH 5.05 to 12.41, which is demonstrated by the time-dependent
      density functional theory (TD-DFT) calculations. Single-crystal X-ray diffraction
      reveals that 1 and 2 are isostructural complexes in which the Ln3+ ions are
      surrounded by six oxygen atoms from three dichelate HTMSA- ligands and two oxygen
      atoms from two solvent molecules forming a distorted square-antiprismatic
      geometry. Complex 1 shows distinct slow magnetic relaxation under a zero dc
      field, while 2 displays field-induced slow magnetic relaxation. Ab initio
      calculations were performed on the two complexes to understand their magnetic
      anisotropy and their different magnetic dynamics.

PMID- 30302454
TI  - Molecular electronic spin qubits from a spin-frustrated trinuclear copper
      complex.
AB  - The trinuclear copper(ii) complex [Cu3(saltag)(py)6]ClO4 (H5saltag = tris(2
      hydroxybenzylidene)triaminoguanidine) was synthesized and characterized by
      experimental as well as theoretical methods. This complex exhibits a strong
      antiferromagnetic coupling (J = -298 cm-1) between the copper(ii) ions, mediated
      by the N-N diazine bridges of the tritopic ligand, leading to a spin-frustrated
      system. This compound shows a T2 coherence time of 340 ns in frozen pyridine
      solution, which extends to 591 ns by changing the solvent to pyridine-d5. Hence,
      the presented compound is a promising candidate as a building block for molecular
      spintronics.

PMID- 30302455
TI  - A simple chemical solution synthesis of nanowire-assembled hierarchical CuO
      microspheres with enhanced photochemical properties.
AB  - Hierarchical micro/nanostructures manifest attractive prospects for
      photocatalytic application. Nevertheless, large-scale hierarchical
      micro/nanostructures for industrial application with facile, low-cost and eco
      friendly routes remain difficult. Herein, nanowire-assembled hierarchical CuO
      microspheres (HCMAW) are synthesized for the first time by CO32- ions induced
      synthesis route. The time-dependent SEM images reveal that the growth mechanism
      for HCMAW is the well-known Ostwald ripening with self-assembly. The specific
      surface area of the HCMAW is 7.265 m2 g-1, which is higher than that of
      hierarchical CuO microspheres assembled with nanosheets (HCMAS) (4.952 m2 g-1)
      prepared by direct self-assembly scheme without the introduction of CO32- ions.
      Meanwhile, the HCMAW possess strong light absorption around a broadband
      wavelength from 300 nm to 800 nm. As a result, the photodegradation activity test
      demonstrates that the HCMAW shows the degradation efficiency of 98.8% for
      rhodamine B (RhB) under white light irradiation for 30 min in the presence of
      H2O2 higher than those of HCMAS (66.3%) and commercial CuO (48.3%) under the same
      condition, which is one of the highest reported till date related to CuO
      nanomaterials for the degradation of RhB. The novel HCMAW synthesized by the ion
      induced protocol is worth being generalized to more assembled hierarchical
      micro/nanostructures for versatile applications.

PMID- 30302456
TI  - Biochemical alterations of Candida albicans during the phenotypic transition from
      yeast to hyphae captured by Fourier transform mid-infrared-attenuated reflectance
      spectroscopy.
AB  - Candida albicans is an opportunistic human pathogen that can become virulent due
      to its ability to switch from a benign yeast to virulent hyphae phenotype. The
      emergence of C. albicans resistant to commonly used antifungal agents has
      necessitated the development of innovative treatments, which must be accompanied
      by an understanding of the molecular changes that occur during the phenotypic
      shift. For this purpose, Fourier transform mid-infrared spectroscopy in
      attenuated total reflectance mode (FT-mIR-ATR) was applied to monitor the
      structural and compositional changes in C. albicans during the yeast-to-hyphae
      transition. FT-mIR-ATR measurements were completed on the whole cell of C.
      albicans (SC5314) during hyphal formation induced by N-acetylglucosamine at 0, 1,
      2, 3, 6 and 24 h. Principal component analysis separated the FT-mIR-ATR spectra
      into four groups that were aligned with the morphological changes captured by
      microscopic imaging. Spectral signatures indicating the structural and
      compositional modifications during the transition were identified mainly in the
      fatty acid region (3100-2800 cm-1), the protein and peptide region (1800-1500 cm
      1), the mixed region (1500-1200 cm-1) and the polysaccharide region (1200-900 cm
      1). A spectral fingerprint of the transition via a heat map was generated based
      on the peak shift in position. Quantitative evaluation of the spectra by curve
      fitting further revealed the dynamics of the cell's main components during the
      transition. This work provides valuable structural and functional information on
      the C. albicans phenotypic transition to hyphae, which has diagnostic
      implications.

PMID- 30302457
TI  - Slow-targeted release of a ruthenium anticancer agent from vitamin B12
      functionalized marine diatom microalgae.
AB  - Herein we report the synthesis of a new biomaterial designed for targeted
      delivery of poorly water-soluble inorganic anticancer drugs, with a focus on
      colorectal cancer. Diatomaceous earth microparticles derived from marine
      microalgae were coated with vitamin B12 (cyanocobalamin) as a tumor targeting
      agent and loaded with the well-known anticancer agents cisplatin, 5-fluorouracil
      (5-FU), and a tris-tetraethyl[2,2'-bipyridine]-4,4'-diamine-ruthenium(ii)
      complex. The successful functionalization of the biomaterial was demonstrated by
      different analytical techniques and by synthesizing an organometallic fluorescein
      analogue of cyanocobalamin detectable by confocal laser scanning microscopy. The
      drug releasing properties were evaluated for all three species. We found that
      while cisplatin and 5-FU are rapidly lost from the material, the ruthenium
      complex showed an unprecedented release profile, being retained in the material
      up to 5 days in aqueous media but readily released in lipophilic environments as
      in the cell membrane. The increased adherence of the B12 coated diatoms to
      colorectal cancer cell line HT-29 and breast cancer cell line MCF-7 was
      demonstrated in vitro. In both cases, the adherence of the B12 modified diatoms
      was at least 3 times higher than that of the unmodified ones and was correlated
      with the increased transcobalamin II (TC(II)) and transcobalamin II receptor
      (TC(II)-R) expression of the targeted tissue. Our results suggest that this type
      of B12 modified diatoms could be a promising tool to achieve targeted delivery of
      water insoluble inorganic complexes to tumor tissues by acting as a micro-shuttle
      interacting with the sites of interest before delivering the drug in the vicinity
      of the tumor tissue.

PMID- 30302458
TI  - Organosoluble tetravalent actinide di- and trifluorides.
AB  - Soluble molecular actinide(iv) fluorides can be prepared in high yield via redox
      or metathesis reactions of silver fluorides with actinide compounds containing
      ancillary iodide or fluorinated thiolate ligands. Two compounds, (py)4UF2I2.2py
      and (py)7Th2F5(SC6F5)3.2py were isolated and characterized by conventional
      methods, powder and low temperature single crystal X-ray diffraction.

PMID- 30302459
TI  - Crystal structure evaluation: calculating relative stabilities and other
      criteria: general discussion.

PMID- 30302460
TI  - A modular assembly pH-sensitive charge reversal siRNA delivery system.
AB  - Cationic lipids and polymers are the most common non-viral vectors for siRNA
      delivery; however, their intense positively charged character may give rise to
      serum-triggered aggregation, immune activation, inflammation stimulation and
      grievous toxicity. An ocean of charge shielding strategies is exploited, but the
      currently available siRNA delivery systems still remain ungratified and
      deficient. Herein, we developed a facile modular assembly strategy for a pH
      sensitive charge reversal siRNA delivery system (PC), which can be easily
      obtained by adjusting the ratios of positively and negatively charged modules.
      This PC is electronegative at neutral pH and reverses to electropositive at an
      acidic pH value with increased tumor cellular uptake. Also, the PC can promote
      efficient intracellular release and cytoplasmic distribution of siRNA, due to its
      fusogenic potential with the lysosome membrane. Moreover, the PC loaded with
      siRNA targeting survivin mRNA (cpusiRNA2) specifically down-regulated the
      expression of survivin, possessing remarkable tumor therapeutic efficacy in vitro
      and in vivo. Accordingly, this handy and effective assembly strategy would
      provide a promising platform for the design of siRNA delivery systems in cancer
      therapy.

PMID- 30302465
TI  - Ubiquinol is superior to ubiquinone to enhance Coenzyme Q10 status in older men.
AB  - Coenzyme Q10 (CoQ10) exerts its functions in the body through the ability of its
      benzoquinone head group to accept and donate electrons. The primary functions are
      to relay electrons for ATP production in the electron transport chain and to act
      as an important lipophilic antioxidant. Ubiquinone, the oxidized form of CoQ10,
      is commonly formulated in commercial supplements, and it must be reduced to
      ubiquinol to exert CoQ10's functions after consumption. Thus, we aimed to examine
      whether as compared to ubiquinone, ubiquinol would be more effective to enhance
      the CoQ10 status in older men. We conducted a double-blind, randomized, crossover
      trial with two 2-week intervention phases and a 2-week washout between
      crossovers. Ten eligible older men were randomized to consume either the
      ubiquinol or ubiquinone supplement at a dose of 200 mg d-1 with one of the main
      meals. A total of 4 blood samples were collected after an overnight fast for the
      determination of ubiquinone and ubiquinol in plasma and PBMC and the assessment
      of FRAP, total thiol, and malondialdehyde (MDA) in plasma and ATP in PBMC. After
      2 weeks of the supplementation, the ubiquinol supplement significantly increased
      plasma ubiquinone 1.7 fold from 0.2 to 0.6 MUmol L-1 and total CoQ10 (the sum of
      2 forms) 1.5 fold from 1.3 to 3.4 MUmol L-1 (p < 0.05) and tended to increase the
      plasma ubiquinol status 1.5 fold from 1.1 to 2.8 MUmol L-1, but did not alter the
      ratio of ubiquinol to total CoQ10. The ubiquinone supplement insignificantly
      increases plasma ubiquinol, ubiquinone, and total CoQ10 and did not affect the
      ratio. Of 10 subjects, six were more responsive to the ubiquinol supplement and 2
      were more so to the ubiquinone. The supplementation of both CoQ10 forms did not
      alter the CoQ10 status in PBMC. FRAP, total thiol, and MDA in plasma and ATP in
      PBMC were not changed during the intervention. The significant increase in plasma
      CoQ10 status observed after the 2-week supplementation suggested that ubiquinol
      appeared to be a better supplemental form to enhance the CoQ10 status than
      ubiquinone in older men. Neither ubiquinol nor ubiquinone supplement affected the
      measured biomarkers of oxidative stress.

PMID- 30302466
TI  - Monomeric nickel hydroxide stabilized by a sterically demanding phosphorus
      nitrogen PN3P-pincer ligand: synthesis, reactivity and catalysis.
AB  - A terminal nickel hydroxide complex (PN3P)Ni(OH) (3) bearing the 2nd generation
      phosphorus-nitrogen PN3P-pincer ligand has been synthesized and structurally
      characterized. As a nucleophile, 3 reacts with CO to afford the hydroxycarbonyl
      complex 4, (PN3P)Ni(COOH). 3 can also activate CO2 and CS2 to produce nickel
      bicarbonate (PN3P)Ni(OCOOH) (5) and bimetallic dithiocarbonate [(PN3P)NiS]2CO (6)
      respectively, as well as to promote aryl isocyanate and isothiocyanate insertion
      into the Ni-OH bond to give the corresponding (PN3P)NiEC(O)NHAr complexes (E = O,
      7; E = S, 8). In addition, 3 catalyzes the nitrile hydration to various amides
      with well-defined intermediates (PN3P)Ni-NHC(O)R (R = Me, 9; R = Ph, 10).

PMID- 30302467
TI  - A new strategy for constructing a disulfide-functionalized ZIF-8 analogue using
      structure-directing ligand-ligand covalent interaction.
AB  - Inter-ligand van der Waals forces play a key role in the synthesis of different
      ZIF types. Here we report an unusual case involving covalent inter-ligand
      interactions through disulfide bond formation in a ZIF-8 analogue. It exhibits
      high CO2 uptake and stepwise adsorption of light hydrocarbons with potential
      applications in ethane/ethylene separation.

PMID- 30302468
TI  - Flexible construction of cellulose photonic crystal optical sensing nano
      materials detecting organic solvents.
AB  - We developed a simple and efficient method to construct 3D and 2D opal and
      inverse opal cellulose photonic crystal films (CPCF) by embedding 3D or 2D
      polymethyl methacrylate (PMMA) colloidal arrays into carboxymethyl cellulose
      (CMC), respectively. The morphology and optical performance of CPCFs were
      characterized by SEM, diffraction spectra, Debye rings, and structural color. The
      brilliant structural colors of CPCFs are visible to the eye in the entire visible
      spectrum, and can be tuned by changing the particle diameters or the pore sizes.
      Attributed to decreased particle spacing and lower average refractive index
      caused by air spheres instead of polymer spheres, the stopbands of the inverse
      opal CPCFs blue-shifted. To the contrary, the particle spacing of 2D inverse opal
      CPCFs increased due to the losing of the connection force of 2D arrays, along
      with decreasing of Debye ring diameters. By alternately being exposed to organic
      solvents of methanol, acetonitrile, butanol, dioxane, and carbon tetrachloride,
      the 3D inverse opal CPCFs displayed an excellent sensing performance with
      instantaneously reversible color changes from violet to red. Their high stability
      and flexibility, efficient visual detection, and wide range of analytes promises
      a new opportunity for optical switching and sensing applications.

PMID- 30302469
TI  - Gel-based cell manipulation method for isolation and genotyping of single
      adherent cells.
AB  - Genetic analysis of single-cells is widely recognized as a powerful tool for
      understanding cellular heterogeneity and obtaining genetic information from rare
      populations. Recently, many kinds of single-cell isolation systems have been
      developed to facilitate single-cell genetic analysis. However, these systems
      mainly target non-adherent cells or cells in a cell suspension. Thus, it is still
      challenging to isolate single-adherent cells of interest from a culture dish
      using a microscope. We had previously developed a single-cell isolation technique
      termed "gel-based cell manipulation" (GCM). In GCM, single-cells could be
      visualized by photopolymerizable-hydrogel encapsulation that made it easier to
      isolate the single-cells. In this study, GCM-based isolation of single-adherent
      cancer cells from a culture dish was demonstrated. Single-adherent cells were
      encapsulated in a photopolymerizable hydrogel using a microscope and isolated
      with high efficiency. Furthermore, whole genome amplification and sequencing for
      the isolated single-adherent cell could be achieved. We propose that the GCM
      based approach demonstrated in this study has the potential for efficient
      analysis of single-adherent cells at the genetic level.

PMID- 30302470
TI  - Assisted pi-stacking: a strong synergy between weak interactions.
AB  - Synergy between a pair of weak non-covalent interactions can predispose a
      molecular self-assembly towards a specific pathway. We report assisted pi
      stacking, a synergy between aromatic pi-stacking and n ->pi* interactions that
      exhibits an unprecedented strength and thermal stability. Natural bond orbital
      analysis reveals the non-additive nature of the interaction.

PMID- 30302472
TI  - Dielectric constant of flagellin proteins measured by scanning dielectric
      microscopy.
AB  - The dielectric constant of flagellin proteins in flagellar bacterial filaments
      ~10-20 nm in diameter is measured using scanning dielectric microscopy. We
      obtained for two different bacterial species (Shewanella oneidensis MR-1 and
      Pseudomonas aeruginosa PAO1) similar relative dielectric constant values
      epsilonSo = 4.3 +/- 0.6 and epsilonPa = 4.5 +/- 0.7, respectively, despite their
      different structure and amino acid sequence. The present results show the
      applicability of scanning dielectric microscopy to nanoscale filamentous protein
      complexes and to general 3D macromolecular protein geometries, thus opening new
      avenues to study the relationship between the dielectric response and protein
      structure and function.

PMID- 30302473
TI  - Gold-loaded microspheres via carbosilane-thioether dendrimers as stabilizers and
      their performance in layer-controllable photonic crystals.
AB  - Gold nanoparticle (Au NP) incorporated photonic crystals (PCs) have been
      extensively studied due to the intricate interplay between the surface plasmon
      resonance of Au NPs and the periodic nanostructure of PCs. Herein, we
      successfully synthesized Au NP decorated poly(styrene-co-(generation 3
      carbosilane-thioether vinyl-terminated dendrimer)) (P(st-co-G3Vi)) microspheres
      via in situ reduction of Au ions based on the strong coordination between the Au
      ions and the sulfur atom in G3Vi dendrimers. These composite Au-doped
      microspheres demonstrate a bumpy surface topography, which gives rise to a higher
      hydrophobicity and could effectively suppress the formation of an ubiquitous
      coffee-ring during the drying process of a colloidal suspension. More
      importantly, layer-controllable PCs were constructed with Au-doped microspheres
      by combining the Langmuir-Blodgett method with a layer-by-layer stacking
      strategy. By manipulating the stacking layers and diameters of microspheres,
      multifarious PCs with different photonic band gaps and reflection intensities
      were obtained, which can serve as an effective substrate for amplified quantum
      dot fluorescence. Further investigation reveals that fluorescence could be
      significantly pronounced by five-layer PCs. This work offers a facile and
      reproducible strategy to prepare Au NP incorporated PCs by in situ synthesis of
      Au NPs within dendrimer-functionalized microspheres, resulting in an enhancement
      of quantum dot fluorescence, which will lead to promising applications in energy
      saving optoelectronic devices.

PMID- 30302474
TI  - Saponins from Boussingaultia gracilis prevent obesity and related metabolic
      impairments in diet-induced obese mice.
AB  - Obesity is a severe public health problem worldwide. Our study aims to assess
      whether a saponin-enriched extract from the leaves of Boussingaultia gracilis
      (SBG) could attenuate obesity and its related metabolic disorders in mice and to
      explore the potential mechanism of this effect. Three-week old male mice were fed
      with a HFD for 7 weeks followed by a 10-week period in which the mice were
      supplemented with distilled water or SBG (250 mg per kg bodyweight). We
      demonstrated that SBG supplementation for 10 weeks mitigated obesity and its
      complications in diet-induced obesity (DIO) mice, such as reducing the hepatic
      damage underlying steatosis, modulating lipid metabolism, enhancing adipocyte
      thermogenesis, restoring insulin sensitivity and glucose homeostasis, and
      alleviating inflammation status. Finally, we established an untargeted
      metabolomics approach based on UPLC-MS to profile the metabolic changes in liver
      tissue and thereby discovered novel potential biomarkers to clarify the
      mechanisms of action of SBG in treating a mouse model of DIO. Thirty-nine
      potential biomarkers and five metabolic pathways contributing to the beneficial
      effect of SBG were discovered and identified.

PMID- 30302475
TI  - 2D molybdenum nitride nanosheets as anode materials for improved lithium storage.
AB  - Two-dimensional (2D) molybdenum nitride (MoN) nanosheets are promising anode
      materials for improved lithium-ion batteries. However, the reported synthesis
      methods of MoN generally rely on high-temperature and complex procedures with low
      cost efficiency. Herein, we report a facile one-pot synthesis of 2D MoN
      nanosheets at a low temperature of 400  degrees C via a solid-state reaction of
      molybdenum disulfide, sulfur and sodium amide in an autoclave. When employed as
      the anode material for lithium ion batteries, the as-developed MoN electrode
      exhibits outstanding cyclability with a high capacity retention of 898 mA h g-1
      over 400 cycles at a current rate of 200 mA g-1 as well as a superb rate
      capability with a capacity of 505 mA h g-1 at a high rate up to 2 A g-1. The
      excellent lithium storage performance of the MoN electrode is attributed to its
      advantageously high conductivity and unique 2D nanostructure.

PMID- 30302476
TI  - Porous Co3O4 nanoplates with pH-switchable peroxidase- and catalase-like
      activity.
AB  - Porous Co3O4 nanoplates were synthesized via a soft template method. By using
      amphiphilic block copolymer F127 colloids as the pore producer, porous Co(OH)2
      nanoplates were prepared. After the annealing procedure, the obtained Co3O4
      reserved the hexagonal shape and a similar size to the Co(OH)2 precursor. The as
      prepared porous Co3O4 nanoplates named Co3O4-F simultaneously possessed
      peroxidase and catalase mimetic activities. Interestingly, these two kinds of
      mimetic enzyme activities could be switched by pH. Meanwhile, temperature and the
      concentrations of Co3O4-F had a significant effect on the switch pH and the dual
      enzyme mimetic catalytic ability. Moreover, Co3O4-F exhibited good peroxidase
      like catalytic activity even in the neutral pH system, providing a new strategy
      for one-step analysis of glucose. A novel one-step colorimetric glucose biosensor
      was fabricated based on the Co3O4-F nanozyme, making the operation of detection
      simpler and easier.

PMID- 30302477
TI  - Bioactive properties and phytochemical assessment of Bacupari-anao (Garcinia
      brasiliensis Mart.) leaves native to Rondonia, Brazil.
AB  - Leaf fractions of Garcinia brasiliensis were evaluated concerning their
      antioxidant, antimicrobial, anti-inflammatory and cytotoxic properties, and the
      most active fraction was then fully characterized regarding its phenolic
      composition using HPLC-DAD-ESI/MSn. The ethyl acetate fraction from partitioning
      of the methanolic leaf extract revealed a strong antioxidant activity that was
      comparable to Trolox, the positive control. This fraction was also able to show a
      significant antimicrobial activity against Gram-positive and Gram-negative
      bacteria and the fungus Candida albicans. However, the dichloromethane fraction
      was found to present the highest anti-inflammatory (83 +/- 9 MUg mL-1) and
      cytotoxic activities, thus presenting slight toxicity using a non-tumor cell
      line. Regarding the phenolic profile, the ethyl acetate fraction presented twelve
      flavonoids, with morelloflavone-7''-O-glucoside (52.1 +/- 0.4 mg g-1) and
      gardinia biflavonoid 2a glucoside (27.5 +/- 0.2 mg g-1) being the major compounds
      identified. These results indicate that leaves of G. brasiliensis might be a
      potential source of natural biomolecules for pharmaceutical and medicinal
      applications.

PMID- 30302479
TI  - High efficiency focusing vortex generation and detection with polarization
      insensitive dielectric metasurfaces.
AB  - The optical vortex beam with an orbital angular momentum, featuring a doughnut
      intensity distribution and a helically structured wavefront, has received
      extensive attention due to its applications in nanoparticle manipulation and
      optical communications. In this paper, we propose high-efficiency polarization
      independent vortex beam generators which are capable of transforming the
      arbitrarily polarized plane wave into a focusing optical vortex beam and an
      abruptly focusing airy vortex beam. Besides, based on holographic metasurfaces,
      we provide a general design scheme for detecting the topological charges. With
      such a design strategy, multichannel topological charge resolved devices are
      demonstrated, which successfully implement the detection of the topological
      charges from -2 to 2. The metasurfaces designed with a simple and effective
      method in light manipulation promise photonic applications in secure
      communications and other related areas.

PMID- 30302480
TI  - Are zinc clusters really amorphous? A detailed protocol for locating global
      minimum structures of clusters.
AB  - We report the results of a conjoint experimental/theoretical effort to assess the
      structures of free-standing zinc clusters with up to 73 atoms. Experiment
      provides photoemission spectra for ZnN- cluster anions, to be used as
      fingerprints in structural assessment, as well as mass spectra for both anion and
      cation clusters. Theory provides both a detailed description of a novel protocol
      to locate global minimum structures of clusters in an efficient and reliable way,
      and its specific application to neutral and charged zinc clusters. Our
      methodology is based on the well-known hybrid EP-DFT (empirical potential-density
      functional theory) approach, in which the approximate potential energy surface
      generated by an empirical Gupta potential is first sampled with unbiased basin
      hopping simulations, and then a selection of the isomers so identified is re
      optimized at a first-principles DFT level. The novelty introduced in our paper is
      a simple but efficient new recipe to obtain the best possible EP parameters for a
      given cluster system, with which the first step of the EP-DFT method is to be
      performed. Our method is able to reproduce experimental measurements at an
      excellent level for most cluster sizes, implying its ability to locate the true
      global minimum structures; meanwhile, if exactly the same method is applied based
      on the existing Gupta potential (fitted to bulk properties), it leads to wrong
      predicted structures with energies between 1 and 2 eV above the correct ones.
      Opposite to what was claimed in the past, our work unequivocally demonstrates
      that Zn clusters are not amorphous, and they rather adopt high symmetry
      structures for most sizes. We show that Zn clusters have a number of exotic,
      unprecedented structural and electronic properties which are not expected for
      clusters of a metallic element, and describe them in detail.

PMID- 30302482
TI  - DNA microarray analysis using a smartphone to detect the BRCA-1 gene.
AB  - DNA microarrays are used to examine changes in gene expression of a large number
      of genes simultaneously by fluorescent labeling of complementary DNAs (cDNAs).
      The major bottleneck in implementing microarray technology in resource-limited
      settings lies in the detection instrument used for generating images of spotted
      oligonucleotides post-hybridization. While various methods such as a lateral flow
      assay have been presented to accomplish point-of-care disease detection, there is
      no simple and effective instrument available to gather spot images maintaining
      the standard microarray procedures. Nanotechnology based sensors connected with a
      portable smartphone readout system have the potential to be implemented in
      microarray technology. Here, we describe a portable fluorescence microarray based
      imaging system connected to a smartphone for detecting breast cancer gene
      expression (BRCA-1) from exon 11. This is based on the interactive binding of
      probe DNA to Cy3-target DNA. A paper-based microfluidics approach was used to
      demonstrate the DNA hybridization assay. The imaging principles of the assembled
      device named "FluoroZen" are similar to those of a fluorescence microscope. It
      uses two light spectrum filters, one to excite the fluorescent dye and the other
      to capture the emission spectrum. The images were acquired by using CCD cameras
      from FluoroZen. The smartphone integrated paper microfluidics platform presented
      here could be translated into clinical settings to perform point-of-care testing.

PMID- 30302483
TI  - Properties and prospects for rhenium(i) tricarbonyl N-heterocyclic carbene
      complexes.
AB  - Re(i) complexes bound to pi-conjugated bidentate N-heterocyclic carbene ligands
      with formulation Re(CO)3(N^NHC)L (where N^NHC represents an imidazole or
      benzimidazole carbene ligand conjugated to a N-based heterocycle such as
      pyridine, pyrimidine, quinoline or quinoxaline) are a relatively new class of
      complexes belonging to the archetypal family of well known luminescent
      Re(CO)3(diim)X species (where diim is a conjugated diimine ligand and X is a
      halogen anion). The complexes Re(CO)3(N^NHC)L are characterised by blue-shifted
      emission compared to Re(CO)3(diim)X, but with shorter excited state lifetime
      decays and lower quantum yields, in contrast to trends expected by the energy gap
      law. Detailed investigations elucidated that these complexes are photochemically
      active and undergo ligand exchange reactions when excited to their lowest metal
      to-ligand charge transfer excited states. This mechanism is entirely different
      from previously known mechanisms of photoactivated ligand substitution reactions
      in Re(i) tricarbonyl complexes. Therefore, the species Re(CO)3(N^NHC)L represent
      a new and unique class of photoactive Re(i) complexes. This feature article
      illustrates the research effort dedicated to the design and synthesis of
      Re(CO)3(N^NHC)L complexes and the elucidation of their photophysical and
      photochemical behaviour by means of a variety of spectroscopic techniques.
      Furthermore, for their unique characteristics, these new complexes have
      demonstrated potential value in several applications including catalysis,
      diagnosis and therapy. These studies will also be illustrated herein.

PMID- 30302484
TI  - pi-Conjugated thiolate amplified spectrophotometry nitrite assay with improved
      sensitivity and accuracy.
AB  - We proposed a pi-conjugation enhanced molar absorption coefficient strategy that
      can effectively improve the sensitivity of the spectrophotometry sensing
      technique. As a case study, the strategy was demonstrated for sensitive nitrite
      detection based on the typical nitrite-thiol reaction.

PMID- 30302485
TI  - Linear heterostructured Ni2Si/Si nanowires with abrupt interfaces synthesised in
      solution.
AB  - Herein, we report a novel approach to form axial heterostructure nanowires
      composed of linearly distinct Ni silicide (Ni2Si) and Si segments via a one-pot
      solution synthesis method. Initially, Si nanowires are grown using Au seeds
      deposited on a Ni substrate with the Si delivery in the solution phase using a
      liquid phenylsilane precursor. Ni silicide then forms axially along the wires
      through progressive Ni diffusion from the growth substrate, with a distinct
      transition between the silicide and pure Si segments. The interfacial abruptness
      and chemical composition of the heterostructure nanowires was analysed through
      transmission electron microscopy, electron diffraction, energy dispersive X-ray
      spectroscopy, aberration corrected scanning transmission electron microscopy and
      atomically resolved electron energy loss spectroscopy. The method represents a
      versatile approach for the formation of complex axial NW heterostructures and
      could be extended to other metal silicide or analogous metal germanide systems.

PMID- 30302486
TI  - Fluid-permeable enzymatic lactate sensors for micro-volume specimen.
AB  - Sensing of lactate in perspiration provides a way to monitor health and control
      exercise. The volume of perspiration is miniscule, and the efficient collection
      of perspiration is desired for its effective sensing. We developed mesh-type
      enzymatic electrodes fabricated on textile meshes and integrated the meshes into
      an enzymatic biofuel cell. We tested them as self-powered lactate sensors for a
      small volume of lactate solution. A fluid-permeable enzymatic anode was
      fabricated based on an insulating textile mesh that was coated with carbon
      nanotubes (CNTs) and lactate oxidase. The anode was further coated with
      polyurethane to increase the linear range by limiting the diffusion of lactate
      while maintaining the advantages of the original textile mesh, such as
      flexibility, stretchability, and permeability. Permeability of the mesh-type
      lactate-oxidizing anode allowed a vertically stacked structure of the anode and a
      previously developed air-breathing cathode. This resulted in a small overall
      device size (1 cm2). The mesh-type sensor was tested using a small flow rate of
      lactate solution, and a moderate linearity of amperometric response for a wide
      concentration range (5 to >=20 mM) was confirmed. The fluid-permeable anode and
      enzymatic biofuel cell show the potential of the sensor for continuous monitoring
      of lactate in perspiration on skin.

PMID- 30302488
TI  - N,S-Atom-coordinated Co9S8 trinary dopants within a porous graphene framework as
      efficient catalysts for oxygen reduction/evolution reactions.
AB  - The intrinsic instability and difficulty in controlling the uniform size
      distributions of cobalt sulfides greatly restrict their application for the
      oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) as a
      bifunctional electrocatalyst in regenerative fuel cells and rechargeable metal
      air batteries. Herein, we synthesize a stable electrocatalyst of N,S-atom
      coordinated Co9S8 trinary dopants within a porous graphene framework (Co9S8@NS
      3DrGO), in which Co9S8 nanoparticles show uniform sizes and distributions. The
      stable Co9S8-based composites are fabricated by a facile soft template-assisted
      strategy, and the attraction of this method is that the intermediate of melamine
      formaldehyde resin (MFR) plays trifunctional roles, including (i) it acts as the
      templated bonding material to crosslink GO sheets together, (ii) it facilitates
      the formation of a core-shell architecture, and (iii) it acts as the N source for
      doping. Catalyst composition and performance are largely dependent on the
      pyrolysis temperature. Extensive investigation elucidates that the mechanism of
      electrocatalytic activity is attributed to: (i) the unique core-shell structure
      of the composites, as well as uniform particle sizes and distributions of Co9S8,
      (ii) the active nitrogen (pyridinic N and graphitic N) contents, and (iii) the
      large surface area and porous architecture. The composite pyrolyzed at 850 
      degrees C exhibits the best electrocatalytic performance, which shows a positive
      ORR half-wave potential (0.826 V), a small OER overpotential (317 mV) at 10 mA cm
      2, and high stability, comparable to the commercial noble catalysts Pt/C and RuO2
      in alkaline media. Furthermore, when applied in zinc-air batteries, it also
      displays a comparable performance to a Pt/C + RuO2 mixture catalyst. This work
      provides an approach to stabilize cobalt sulfides and control their particle
      sizes and distributions by ingeniously employing the soft template of MFR and
      pyrolyzing them at various temperatures.

PMID- 30302487
TI  - An integrated adipose-tissue-on-chip nanoplasmonic biosensing platform for
      investigating obesity-associated inflammation.
AB  - Although many advanced biosensing techniques have been proposed for cytokine
      profiling, there are no clinically available methods that integrate high
      resolution immune cell monitoring and in situ multiplexed cytokine detection
      together in a biomimetic tissue microenvironment. The primary challenge arises
      due to the lack of suitable label-free sensing techniques and difficulty for
      sensor integration. In this work, we demonstrated a novel integration of a
      localized-surface plasmon resonance (LSPR)-based biosensor with a biomimetic
      microfluidic 'adipose-tissue-on-chip' platform for an in situ label-free, high
      throughput and multiplexed cytokine secretion analysis of obese adipose tissue.
      Using our established adipose-tissue-on-chip platform, we were able to monitor
      the adipose tissue initiation, differentiation, and maturation and simulate the
      hallmark formation of crown-like structures (CLSs) during pro-inflammatory
      stimulation. With integrated antibody-conjugated LSPR barcode sensor arrays, our
      platform enables simultaneous multiplexed measurements of pro-inflammatory (IL-6
      and TNF-alpha) and anti-inflammatory (IL-10 and IL-4) cytokines secreted by the
      adipocytes and macrophages. As a result, our adipose-tissue-on-chip platform is
      capable of identifying stage-specific cytokine secretion profiles from a complex
      milieu during obesity progression, highlighting its potential as a high
      throughput preclinical readout for personalized obesity treatment strategies.

PMID- 30302489
TI  - Divergent synthesis of N-heterocycles by Pd-catalyzed controllable cyclization of
      vinylethylene carbonates.
AB  - Here, we report a palladium-catalyzed controllable cyclization of vinyl ethylene
      carbonates that proceeds through formal migration [2+3] and [5+2] cycloadditions,
      respectively, under mild conditions. The transformation described here affords a
      series of synthetically versatile 5,7-membered N-heterocycles which are found in
      natural products and pharmaceuticals with biological and medicinal properties.

PMID- 30302490
TI  - Inhibition and decision-processing speed are associated with performance on
      dynamic posturography in older adults.
AB  - Changes in cognition due to age have been associated with falls and reduced
      standing postural control. Sensory integration is one component of postural
      control that may be influenced by certain aspects of cognitive functioning. This
      study investigated associations between measures of cognitive function and
      sensory integration capabilities for healthy young and older adults. Dynamic
      posturography was performed using the Equitest Sensory Organization Test (SOT)
      protocol to evaluate sensory integration during standing using sway-referencing
      of the platform and/or visual scene to alter somatosensory and visual inputs. The
      Equilibrium Score was used as a measure of sway. Cognitive testing examined
      aspects of cognitive function that have been associated with falls in older
      adults. A correlational analysis investigated associations between the cognitive
      measures and postural sway during the altered sensory conditions of the SOT. For
      older subjects only, slower decision-processing speed was associated with
      increased sway during SOT conditions whenever somatosensation was altered.
      Reduced perceptual inhibition was associated with increased sway whenever
      somatosensation was intact, and particularly when vision was altered in the
      presence of somatosensation. Visuospatial construct ability was associated with
      sway only when the eyes were closed during altered somatosensation. Task
      switching was associated with sway only when vision and somatosensation were
      intact. With increased age, deficits in decision speed and inhibition appear
      associated with the sensory integration crucial for balance maintenance.
      Associations are modulated by the availability of somatosensation and vision.
      These associations define situations and individual differences in aspects of
      cognition that may relate to situational loss of balance in older adults.

PMID- 30302491
TI  - Is oxidized low-density lipoprotein the connection between atherosclerosis,
      cardiovascular risk and nephrolithiasis?
AB  - Nephrolithiasis is considered a systemic disease. A link has been established
      between nephrolithiasis, cardiovascular disease (CVD), the metabolic syndrome and
      atherosclerosis. A significant correlation has been found between the high levels
      of oxidized low-density lipoprotein (oxLDL) and CVD and atherosclerosis,
      including coronary and femoral artery disease. To the best of our knowledge,
      oxLDL has not been evaluated in patients with nephrolithiasis. This study aimed
      to evaluate serum levels of oxLDL, anti-oxLDL antibodies (oxLDL-ab) and other
      markers of atherosclerosis in patients with nephrolithiasis, according to the
      severity of the disease. The population sample consisted of 94 patients of 30-70
      years of age with no symptoms of CVD who presented with renal calculi documented
      by ultrasonography, abdominal X-ray or computed tomography. The patients were
      divided into two groups: Group 1 (>= 3 stones) and Group 2 (1-2 stones). A
      comparison control group was formed with 21 healthy individuals. Enzyme-linked
      immunosorbent assays were used to assess oxLDL and oxLDL-ab. Lipid peroxidation
      indexes were also analyzed. Median serum oxLDL values were higher in Groups 1 and
      2 compared to the control group (>= 3 stones, p = 0.02; 1-2 stones, p = 0.03).
      Median serum anti-oxLDL antibody levels were lower in the patients in Group 1
      compared to the controls (p = 0.03). There was no significant difference in the
      oxLDL/oxLDL-ab ratio between patients and controls. These findings suggest that
      this may be the link between nephrolithiasis and the greater incidence of
      atherosclerosis and cardiovascular disease in patients with kidney stones.

PMID- 30302492
TI  - [Safety and effectiveness of aquablation for prostatic hyperplasia].

PMID- 30302493
TI  - [Efficacy of metaphylaxis in recurrent urolithiasis].

PMID- 30302494
TI  - [Immunotherapy for locally advanced and metastasized bladder cancer].
AB  - Urothelial carcinoma of the bladder is difficult to treat in advanced and
      metastatic stages. Several factors play a role: age, multimorbidity including
      impaired renal function and neuropathy make access to life-prolonging
      chemotherapy impossible in many cases. Improvements of response rates and overall
      survival in the second-line setting are not much different compared to best
      supportive care. However, the therapeutic landscape has changed dramatically
      during the last 2 years. Immunotherapies represented by checkpoint inhibitors
      have showed positive trial outcomes and have been approved by EMA (European
      Medicines Agency). Both in second-line therapy after platinum-based chemotherapy
      and in first-line therapy in unfit patients, these drugs can be used. New
      concepts with combinations of immunotherapeutic compounds are currently being
      examined in various trials. If we follow the data of other malignancies (melanoma
      and non-small cell lung cancer), the future looks optimistic.

PMID- 30302495
TI  - Quality of life after staged bilateral total knee arthroplasty: a minimum five
      year follow-up study of seventy-eight patients.
AB  - PURPOSE: Although many studies have been performed to evaluate the quality of
      life (QOL) and patient satisfaction after total knee arthroplasty (TKA), almost
      all evaluations were performed in patients after unilateral TKA or in patients
      after mixed unilateral and bilateral TKA. Accordingly, this study aimed to
      evaluate QOL after staged bilateral TKA. METHODS: A total of 78 patients who
      underwent staged bilateral TKA for varus knee osteoarthritis were included in
      this study. All patients had longitudinal follow-up evaluations for at least five
      years. QOL was assessed by the Japanese Knee Osteoarthritis Measure (JKOM), a
      disease-specific and patient-derived QOL measure for Japanese patients.
      Conventional objective outcome scales, including the Knee Society Score and the
      Timed Up and Go test, were also assessed. In addition, QOL and objective outcomes
      were compared between the younger (<= 80 years, average 75.8 years) and older (>
      80 years, average 84.7 years) age groups at the final follow-up. RESULTS:
      Improvements in both JKOM and objective outcomes reached a plateau one year after
      staged bilateral TKA. Improvements were prolonged for more than five years. There
      were no statistically significant differences in JKOM or objective outcomes
      between the younger and older age groups, despite an 8.9-year difference in the
      average age. CONCLUSIONS: This was the first longitudinal study to evaluate QOL
      and objective outcomes after staged bilateral TKA for a period of at least five
      years. Improvements in QOL and objective outcomes reached a plateau one year
      after staged bilateral TKA and were prolonged for more than five years. No
      significant differences were observed in outcome scores between the younger and
      older age groups.

PMID- 30302496
TI  - [Treatment of cutaneous malignant melanoma in the head and neck region : An
      update].
AB  - Major progress has been made in the treatment of malignant melanoma during recent
      years. On the one hand, reliable evidence-based recommendations regarding
      surgical resection as well as lymph node management have been established on the
      basis of results from randomized multicenter studies. On the other hand, the
      advent of targeted therapies has led to spectacular improvements in the treatment
      of metastasized melanomas. Knowledge concerning treatment algorithms and updates
      thereof is also essential for maxillofacial surgeons. The German S3 guideline on
      diagnosis and treatment of melanoma was published in 2013 and revised in 2016 and
      2018. This article informs readers about these developments and addresses the
      items relevant for treatment of head and neck melanomas in particular.

PMID- 30302497
TI  - Extensor hallucis longus-transfer for tibialis anterior tendon rupture repair.
AB  - OBJECTIVE: Restore the function of the tibialis anterior muscle, which is
      responsible for dorsiflexion and inversion of the foot. INDICATIONS: Spontaneous
      or traumatic rupture of the tibialis anterior tendon. CONTRAINDICATIONS: Patients
      with multimorbidity or lack of functional demands. SURGICAL TECHNIQUE: Direct
      repair of the tibialis anterior tendon with fiber-wire suture and augmentation
      with extensor hallucis longus tendon, potentially in combination with reinsertion
      of the tibialis anterior tendon in the medial cuneiform. POSTOPERATIVE
      MANAGEMENT: Six weeks of non-weight-bearing: 3 weeks of cast immobilization with
      ankle in 10 degrees  dorsiflexion, followed by 3 weeks of splint immobilization
      and passive mobilization. Then stepwise increase in weight-bearing over a period
      of 2-3 weeks. RESULTS: In 8 patients postoperative results with a mean follow-up
      of 13.5 months were available. One patient showed a rerupture of the augmented
      tendon. The mean American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot
      score was 81.0 (range 67-88). The median ankle dorsiflexion muscle strength was
      67% (range 29.3-85.5%) compared to the nonoperated leg. All patients, except the
      one that experienced rerupture, were very satisfied or satisfied with the result.

PMID- 30302498
TI  - Opposing roles of eosinophils in cancer.
AB  - Eosinophils are a subset of granulocytes mostly known for their ability to combat
      parasites and induce allergy. Although they were described to be related to
      cancer more than 100 years ago, their role in tumors is still undefined. Recent
      observations revealed that they display regulatory functions towards other immune
      cell subsets in the tumor microenvironment or direct cytotoxic functions against
      tumor cells, leading to either antitumor or protumor effects. This paradoxical
      role of eosinophils was suggested to be dependent on the different factors in the
      TME. In addition, the clinical relevance of these cells has been recently
      addressed. In most cases, the accumulation of eosinophils both in the tumor
      tissue, called tumor-associated tissue eosinophilia, and in the peripheral blood
      were reported to be prognostic markers for a better outcome of cancer patients.
      In immunotherapy of cancer, particularly in therapy with immune checkpoint
      inhibitors, eosinophils were even shown to be a potential predictive marker for a
      beneficial clinical response. A better understanding of their role in cancer
      progression will help to establish them as prognostic and predictive markers and
      to design strategies for targeting eosinophils.

PMID- 30302500
TI  - Congo Red affects the growth, morphology and activity of glucosamine-6-phosphate
      synthase in the human pathogenic fungus Sporothrix schenckii.
AB  - Sporothrix schenckii is the etiological agent of sporotrichosis, a mycosis of
      humans and other mammals. Little is known about the responses of this
      thermodimorphic pathogen to perturbations in the cell wall (CW) by different
      stress conditions. Here we describe the effect of Congo Red (CR) on the fungal
      growth, morphogenesis and activity of glucosamine-6-phosphate (GlcN-6-P)
      synthase. Under conditions of yeast development, 15 uM CR abolished conidia (CN)
      germination, but when yeast cells were first obtained in the absence of the dye
      and then post-incubated in its presence, yeasts rapidly differentiated into
      mycelial cells. On the other hand, under conditions of mycelium development, 150
      uM CR did not affect CN germination, but filamentous cells underwent structural
      changes characterized by a distorted CW contour, the loss of polarity and the
      formation of red-pigmented, hyphal globose structures. Under these conditions, CR
      also induced a significant and transient increase in the activity of GlcN-6-P
      synthase, an essential enzyme in CW biogenesis.

PMID- 30302499
TI  - Assessment of myelination progression in subcortical white matter of children
      aged 6-48 months using T2-weighted imaging.
AB  - PURPOSE: This study aims to provide a screening scoring method by assessing the
      age-related change of subcortical white matter (WM) myelination via T2-weighted
      imaging (T2WI). METHODS: This study retrospectively recruited 109 children aged 6
      48 months without abnormalities on MRI. Based on Parazzini's study, we developed
      a modified T2WI-based method to assess subcortical WM myelination (frontal,
      temporal, parietal, occipital lobes, and insula) by scoring WM's signal changes.
      Inter- and intra-observer agreements were evaluated by Bland-Altman plot. Age
      related changes of myelination score were explored by locally weighted
      scatterplot smoothing (LOESS), linear regression, and Spearman correlation
      coefficients (r). Relationships between diffusion tensor imaging (DTI) metrics
      and total myelination score were investigated to further validate practicability
      of the scoring method by tract-based spatial statistics (TBSS). RESULTS: This
      method showed good intra-observer (mean difference = 0.18, SD = 0.95) and inter
      observer agreements (mean difference = - 0.06, SD = 1.01). The LOESS and linear
      regression results indicated that myelination proceeded in two phases: a period
      of rapid growth (6-20 months; slope = 0.561) and one of slower growth (21-48
      months; slope = 0.097). Significant correlations between myelination score and
      age were observed in whole subcortical WM (r = 0.945; P < 0.001) and all regional
      subcortical WM (r_mean = 0.819, range, 0.664-0.928; P < 0.001). TBSS found
      significant correlations of WM-DTI metrics with myelination score during the
      range of 6-20 months, while no significant correlation was observed in 21-48
      months. CONCLUSION: The modified T2WI-based screening scoring method is easily
      feasible to assess myelination progression of subcortical WM, especially suitable
      for children aged 6-20 months. It may show potential in identifying individual
      developmental abnormalities by scoring assessment in the future clinical
      practice.

PMID- 30302502
TI  - Discussion of One-Stage Combined Postbariatric Surgery: A Series of 248
      Procedures in 55 Cases.

PMID- 30302501
TI  - Ancestral and Compensatory Mutations that Promote Antiviral Resistance in
      Influenza N1 Neuraminidase Revealed by a Phylonumerics Approach.
AB  - Implementation of a new phylonumerics approach to construct a mass tree
      representing over 6000 H1N1 human influenza strains has enabled ancestral and
      compensatory descendant mutations to be identified in N1 neuraminidase that
      promote antiviral resistance and restore viral fitness. Adjacent to the H275Y
      resistance mutation site, mutations S299A and S247N, respectively, lead the
      evolution of oseltamivir-resistant strains and restore viral fitness to those
      strains thereafter. Importantly the mass tree phylonumerics approach can identify
      such mutations globally, without any positional bias, so that functionally linked
      or compensatory mutations remote in the sequence or structure of the protein can
      be identified and interrogated. This is achieved using mass map datasets commonly
      employed for protein identification in proteomics applications, thus avoiding the
      need for either gene or protein sequences that are central to other phylogenetic
      methods.

PMID- 30302503
TI  - Transcranial color-coded duplex sonography for bedside monitoring of central
      nervous system infection as a consequence of decompressive craniectomy after
      traumatic brain injury.

PMID- 30302504
TI  - How to proceed with long-term anticoagulation in patient after total gastrectomy
      and atrial fibrillation?

PMID- 30302505
TI  - The Case for Cardiac Xenotransplantation in Neonates: Is Now the Time to
      Reconsider Xenotransplantation for Hypoplastic Left Heart Syndrome?
AB  - Neonatal cardiac transplantation for hypoplastic left heart syndrome (HLHS) is
      associated with excellent long-term survival compared to older recipients.
      However, heart transplantation for neonates is greatly limited by the critical
      shortage of donor hearts, and by the associated mortality of the long pre
      transplant waiting period. This led to the development of staged surgical
      palliation as the first-line surgical therapy for HLHS. Recent advances in
      genetic engineering and xenotransplantation have provided the potential to
      replicate the excellent results of neonatal cardiac allotransplantation while
      eliminating wait-list-associated mortality through genetically modified pig-to
      human neonatal cardiac xenotransplantation. The elimination of the major pig
      antigens in addition to the immature B-cell response in neonates allows for the
      potential to induce B-cell tolerance. Additionally, the relatively mature
      neonatal T-cell response could be reduced by thymectomy at the time of operation
      combined with donor-specific pig thymus transplantation to "reprogram" the host's
      T-cells to recognize the xenograft as host tissue. In light of the recent
      significantly increased graft survival of genetically-engineered pig-to-baboon
      cardiac xenotransplantation, we propose that now is the time to consider devoting
      research to advance the potential clinical application of cardiac
      xenotransplantation as a treatment option for patients with HLHS. Employing
      cardiac xenotransplantation could revolutionize therapy for complex congenital
      heart defects and open a new chapter in the field of pediatric cardiac
      transplantation.

PMID- 30302507
TI  - A density assignment method for dose monitoring in head-and-neck radiotherapy.
AB  - BACKGROUND AND PURPOSE: During head-and-neck (H&N) radiotherapy, the parotid
      glands (PGs) may be overdosed; thus, a tool is required to monitor the delivered
      dose. This study aimed to assess the dose accuracy of a patient-specific density
      assignment method (DAM) for dose calculation to monitor the dose to PGs during
      treatment. PATIENTS AND METHODS: Forty patients with H&N cancer received an
      intensity modulated radiation therapy (IMRT), among whom 15 had weekly CTs. Dose
      distributions were calculated either on the CTs (CTref), on one-class CTs (1C-CT,
      water), or on three-class CTs (3C-CT, water-air-bone). The inter- and intra
      patient DAM uncertainties were evaluated by the difference between doses
      calculated on CTref and 1C-CTs or 3C-CTs. PG mean dose (Dmean) and spinal cord
      maximum dose (D2%) were considered. The cumulated dose to the PGs was estimated
      by the mean Dmean of the weekly CTs. RESULTS: The mean (maximum) inter-patient
      DAM dose uncertainties for the PGs (in cGy) were 23 (75) using 1C-CTs and 12 (50)
      using 3C-CTs (p <= 0.001). For the spinal cord, these uncertainties were 118
      (245) and 15 (67; p <= 0.001). The mean (maximum) DAM dose uncertainty between
      cumulated doses calculated on CTs and 3C-CTs was 7 cGy (45 cGy) for the PGs.
      Considering the difference between the planned and cumulated doses, 53% of the
      ipsilateral and 80% of the contralateral PGs were overdosed by +3.6 Gy (up to 8.2
      Gy) and +1.9 Gy (up to 5.2 Gy), respectively. CONCLUSION: The uncertainty of the
      three-class DAM appears to be clinically non-significant (<0.5 Gy) compared with
      the PG overdose (up to 8.2 Gy). This DAM could therefore be used to monitor PG
      doses and trigger replanning.

PMID- 30302508
TI  - 35. Jahrestagung der Osterreichischen Gesellschaft fur Radioonkologie,
      Radiobiologie und Medizinische Radiophysik.

PMID- 30302509
TI  - Aluminium toxicokinetics after intramuscular, subcutaneous, and intravenous
      injection of Al citrate solution in rats.
AB  - Knowledge of dose linearity, plasma clearance, rate and extent of subcutaneous
      (SC) and intramuscular (IM) absorption of soluble aluminium (Al) citrate is
      considered a prerequisite for evaluation of toxicokinetic data obtained from SC
      or IM administration of Al adjuvants in medicinal products. Therefore, total Al
      plasma kinetics was investigated after SC, IM, and IV administration of single Al
      doses (36 and 360 ug/kg IM or SC; 30 and 300 ug/kg IV) given as citrate solution
      in rats. Control groups receiving vehicle (saline) were run in parallel to
      monitor background plasma Al levels over time resulting from dietary intake.
      Evaluation of Al plasma profiles was done by both non-compartmental analysis of
      baseline-corrected data and simultaneous model fitting to the raw data using a
      population kinetics approach. High and dose-independent total plasma clearance
      (6.6 mL/min/kg) was observed after IV administration corresponding to 60-82% of
      normal rat GFR. This supports the previous assumptions that parenterally
      administered Al citrate is more rapidly cleared from plasma than other Al species
      (e.g., chloride or lactate). Furthermore, plasma exposure of Al (Cmax and AUC0
      inf) increased dose-proportionally at all administration routes. Fast and
      complete absorption of Al was observed at each dose level after both SC and IM
      administration (bioavailability estimates: 88 and 110%). Estimates for the first
      order absorption rate constant ka correspond to absorption half-lives of 36 min
      (SC) and <= 13 min (IM). There was no increase in tissue Al content (whole bone
      and brain) after 36 ug/kg IM compared to control rats.

PMID- 30302510
TI  - English on cigarette packs from six non-Anglophone low- and middle-income
      countries.
AB  - OBJECTIVES: Low- and middle-income countries (LMICs) are vital to the global
      tobacco market. The pack is key to cigarette branding, and review of cigarette
      packs revealed English as a common feature. The prevalence of English and its
      potential branding utility is explored. METHODS: Every available unique cigarette
      pack was purchased from diverse retailers in six LMICs where English is not the
      official language (Bangladesh, Brazil, China, Egypt, Ukraine, Vietnam). Packs'
      front panels were coded for English on pack fronts. English penetration was
      quantified by country and a comparison of English use between multinational and
      national brands was undertaken. A qualitative analysis of symbolic and
      utilitarian usage of English was conducted. RESULTS: Of 1303 unique cigarette
      packs analyzed, 67% (n = 876) included some English. English text conveyed
      product information and usage instruction. English was more prevalent for
      multinational brands. Qualitatively, English use frequently connected cigarettes
      with concepts of quality, style, luxury, and aspirational lifestyle. CONCLUSIONS:
      Restricting English use should be incorporated into plain packaging policy to
      protect populations from deceptive branding practices, specifically presenting
      cigarettes as an aspirational product.

PMID- 30302511
TI  - Acute and long-lasting effects of oxytocin in cortico-limbic circuits:
      consequences for fear recall and extinction.
AB  - The extinction of conditioned fear responses entrains the formation of safe new
      memories to decrease those behavioral responses. The knowledge in neuronal
      mechanisms of extinction is fundamental in the treatment of anxiety and fear
      disorders. Interestingly, the use of pharmacological compounds that reduce
      anxiety and fear has been shown as a potent co-adjuvant in extinction therapy.
      However, the efficiency and mechanisms by which pharmacological compounds promote
      extinction of fear memories remains still largely unknown and would benefit from
      a validation based on functional neuronal circuits, and the neurotransmitters
      that modulate them. From this perspective, oxytocin receptor signaling, which has
      been shown in cortical and limbic areas to modulate numerous functions (Eliava et
      al. Neuron 89(6):1291-1304, 2016), among them fear and anxiety circuits, and to
      enhance the salience of social stimuli (Stoop Neuron 76(1):142-59, 2012), may
      offer an interesting perspective. Experiments in animals and humans suggest that
      oxytocin could be a promising pharmacological agent at adjusting memory
      consolidation to boost fear extinction. Additionally, it is possible that long
      term changes in endogenous oxytocin signaling can also play a role in reducing
      expression of fear at different brain targets. In this review, we summarize the
      effects reported for oxytocin in cortico-limbic circuits and on fear behavior
      that are of relevance for the modulation and potential extinction of fear
      memories.

PMID- 30302506
TI  - Target identification for the diagnosis and intervention of vulnerable
      atherosclerotic plaques beyond 18F-fluorodeoxyglucose positron emission
      tomography imaging: promising tracers on the horizon.
AB  - Cardiovascular disease is the major cause of morbidity and mortality in developed
      countries and atherosclerosis is the major cause of cardiovascular disease.
      Atherosclerotic lesions obstruct blood flow in the arterial vessel wall and can
      rupture leading to the formation of occlusive thrombi. Conventional diagnostic
      tools are still of limited value for identifying the vulnerable arterial plaque
      and for predicting its risk of rupture and of releasing thromboembolic material.
      Knowledge of the molecular and biological processes implicated in the process of
      atherosclerosis will advance the development of imaging probes to differentiate
      the vulnerable plaque. The development of imaging probes with high sensitivity
      and specificity in identifying high-risk atherosclerotic vessel wall changes and
      plaques is crucial for improving knowledge-based decisions and tailored
      individual interventions. Arterial PET imaging with 18F-FDG has shown promising
      results in identifying inflammatory vessel wall changes in numerous studies and
      clinical trials. However, due to its limited specificity in general and its
      intense physiological uptake in the left ventricular myocardium that impair
      imaging of the coronary arteries, different PET tracers for the molecular imaging
      of atherosclerosis have been evaluated. This review describes biological,
      chemical and medical expertise supporting a translational approach that will
      enable the development of new or the evaluation of existing PET tracers for the
      identification of vulnerable atherosclerotic plaques for better risk prediction
      and benefit to patients.

PMID- 30302512
TI  - Human Microbiome: Composition and Role in Inflammatory Skin Diseases.
AB  - This review focuses on recent evidences about human microbiome composition and
      functions, exploring the potential implication of its impairment in some diffuse
      and invalidating inflammatory skin diseases, such as atopic dermatitis,
      psoriasis, hidradenitis suppurativa and acne. We analysed current scientific
      literature, focusing on the current evidences about gut and skin microbiome
      composition and the complex dialogue between microbes and the host. Finally, we
      examined the consequences of this dialogue for health and skin diseases. This
      review highlights how human microbes interact with different anatomic niches
      modifying the state of immune activation, skin barrier status, microbe-host and
      microbe-microbe interactions. It also shows as most of the factors affecting gut
      and skin microorganisms' activity have demonstrated to be effective also in
      modulating chronic inflammatory skin diseases. More and more evidences
      demonstrate that human microbiome plays a key role in human health and diseases.
      It is to be expected that these new insights will translate into diagnostic,
      therapeutic and preventive measures in the context of personalized/precision
      medicine.

PMID- 30302513
TI  - The Key for Preventing Recanalization May be High Packing Density: Reply to
      Rajagopal et al.

PMID- 30302514
TI  - Variant termination of first and second jejunal veins into a "pancreatic portal
      vein".
AB  - Jejunal veins usually terminate into the superior mesenteric vein. Here, an
      unusual termination of first and second jejunal veins into a pancreatic portal
      vein has been presented. The common vein formed by the first and second jejunal
      veins could be named as pancreatic portal vein because it divided into two
      branches in front of the third part of the duodenum and these two branches
      entered the head of the pancreas and further divided into smaller branches before
      anastomosing with the tributaries of pancreatico-duodenal veins. The knowledge of
      this rare vein could be useful to radiologists and surgeons.

PMID- 30302515
TI  - [Erratum to: Effectiveness and tolerability of electroconvulsive therapy :
      Influence of clinical response from the patient's point of view].
AB  - BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective, yet still
      controversial therapy for both the general public and psychiatrists. In this
      study, we investigated the patients' view regarding effectiveness and
      tolerability of electroconvulsive therapy under consideration of individual
      clinical response. MATERIAL AND METHODS: In 31 patients with major depression,
      subjective effectiveness and tolerability were assessed via a differentiated
      questionnaire prior to, during, and after ECT. Symptoms were rated using the
      Montgomery-Asberg depression rating scale (MADRS) and the Beck depression
      inventory II (BDI-II) RESULTS: Patients assessed ECT to be generally effective
      both before and after the treatment. This view was independent of their
      individual treatment success. In contrast, patients' rating of individual
      effectiveness depended on the objective improvement of their symptoms. Side
      effects were rated to be generally slight to moderate. CONCLUSION: Against the
      background of persisting criticism towards ECT, the viewpoint of involved
      patients provides us with important references for an appropriate judgement of
      this therapy. The results suggest a good benefit-risk ratio for ECT from the
      patients' perspective.

PMID- 30302516
TI  - [Patho- and therapyepigenetics of mental disorders].
AB  - Epigenetic mechanisms, such as DNA methylation and histone modifications are
      biochemical alterations of the DNA or its spatial structure. They regulate gene
      function, can be modified by environmental influences and are temporally dynamic.
      In this review, the current state of knowledge regarding the role of epigenetics
      in the pathogenesis of mental disorders is summarized exemplarily for
      schizophrenia, depression, anxiety disorders and posttraumatic stress disorder.
      Additionally, findings on epigenetic alterations in the course of
      pharmacotherapeutic and psychotherapeutic interventions are presented. Epigenetic
      mechanisms have a central function at the crossroads between genes and
      environment and consequently in the vulnerability-stress model of mental
      disorders. Prospectively, in line with a precision medicine approach epigenetic
      profiles may represent useful markers of disease risk and therapy response or
      even constitute new druggable targets.

PMID- 30302517
TI  - [Video-assisted patient education in anesthesia : How do medical users assess the
      procedure?]
AB  - BACKGROUND: Video-assisted patient education (VaPE) has in the past been a
      subject of many studies. Compared to conventional methods, most authors reported
      a better transfer of information, some found increased patient satisfaction and a
      time-sparing effect. There was no increase in anxiety caused by VaPE. Some
      authors even found a reduction of anxiety levels before anesthesia. All
      publications to date have focused on the patient's point of view. There have been
      no reports on how anesthetists as users assess VaPE. METHODS: In this study 22
      anesthesia departments using VaPE were contacted. A total of 122 anesthetists
      were sent questionnaires of which 81 (66%) were completed and returned. The
      anesthetists were first questioned about the characteristics of the workplace,
      the frequency of preanesthesia patient contacts, the content of the videos, the
      technique of video presentation and their own professional experience. After this
      the anesthetists were asked to assess five statements concerning: usefulness of
      VaPE, economy of time, transfer of knowledge, induction of anxiety and influence
      on the quality of the consent interview. In each category there were 4 choices:
      fully agree, partly agree, partly disagree and fully disagree. The first two
      choices were evaluated as positive and the second two as negative answers. The
      anesthetists were also asked to state the most valued characteristics of VaPE.
      Out of eight given options they were to select the most favored three. A final
      question was whether in their opinion VaPE could be recommended to non-users.
      RESULTS: Of the anesthetists 97.5% stated that disclosure interviews
      predominantly took place in the preoperative anesthetic clinic and 73% performed
      15 or more patient interviews per day. Videos about general anesthesia were
      applied by 70%, about non-obstetric regional anesthesia by 56% and about
      obstetric epidural anesthesia by 59%. The videos were presented to groups of
      patients via large screens by 27%, individually with CD players or tablet
      computers by 51% or with both methods (22%). Of the anesthetists 69% had 5 years
      or more professional experience, 97.5% found VaPE useful for patients education,
      92.5% observed a time-saving effect for the following interview and 96% stated
      that after watching the video patients were better informed. An increase of
      anxiety caused by VaPE was noted by 46% whereas 54% found no such effect. As to
      the quality of interview 50% reported an advantage in focusing on the patient's
      individual risk profile and the other 50% reported no advantage. The ranking of
      the main advantages was 1) better patient information, 2) time-saving effect, 3)
      helpful for patient education, followed by 4) increased patient satisfaction, 5)
      better understanding of anesthesiology, 6) individualization of the interview and
      7) helpful in questions of legal liability. The answer option "no advantage" was
      not chosen at all. Of the participants 82.5% would recommend VaPE unconditionally
      (fully agree), 17.5% would give a conditional recommendation to colleagues and no
      one would not recommend VaPE. CONCLUSION: This survey among anesthetists
      confirmed most results obtained from patient-based studies: medical users
      attributed to VaPE a better information transfer and a time-sparing effect.
      Furthermore, users regarded VaPE as helpful for the preanesthesia interview. As
      compared to the patient-based results, however, many anesthetists seem to
      overrate the anxiety, caused by disclosure videos. From the users' point of view,
      VaPE is a highly appreciated method for patient education which can be
      recommended to colleagues.

PMID- 30302518
TI  - Microbial forensics: new breakthroughs and future prospects.
AB  - Recent advances in genetic data generation, through massive parallel sequencing
      (MPS), storage and analysis have fostered significant progresses in microbial
      forensics (or forensic microbiology). Initial applications in circumstances of
      biocrime, bioterrorism and epidemiology are now accompanied by the prospect of
      using microorganisms (i) as ancillary evidence in criminal cases; (ii) to clarify
      causes of death (e.g., drownings, toxicology, hospital-acquired infections,
      sudden infant death and shaken baby syndromes); (iii) to assist human
      identification (skin, hair and body fluid microbiomes); (iv) for geolocation
      (soil microbiome); and (v) to estimate postmortem interval (thanatomicrobiome and
      epinecrotic microbial community). When compared with classical microbiological
      methods, MPS offers a diverse range of advantages and alternative possibilities.
      However, prior to its implementation in the forensic context, critical efforts
      concerning the elaboration of standards and guidelines consolidated by the
      creation of robust and comprehensive reference databases must be undertaken.

PMID- 30302519
TI  - Characterization and use of a bacterial lignin peroxidase with an improved
      manganese-oxidative activity.
AB  - Peroxidases are well-known biocatalysts produced by all organisms, especially
      microorganisms, and used in a number of biotechnological applications. The enzyme
      DypB from the lignin-degrading bacterium Rhodococcus jostii was recently shown to
      degrade solvent-obtained fractions of a Kraft lignin. In order to promote the
      practical use, the N246A variant of DypB, named Rh_DypB, was overexpressed in E.
      coli using a designed synthetic gene: by employing optimized conditions, the
      enzyme was fully produced as folded holoenzyme, thus avoiding the need for a
      further time-consuming and expensive reconstitution step. By a single
      chromatographic purification step, > 100 mg enzyme/L fermentation broth with a >
      90% purity was produced. Rh_DypB shows a classical peroxidase activity which is
      significantly increased by adding Mn2+ ions: kinetic parameters for H2O2, Mn2+,
      ABTS, and 2,6-DMP were determined. The recombinant enzyme shows a good
      thermostability (melting temperature of 63-65  degrees C), is stable at pH 6-7,
      and maintains a large part of the starting activity following incubation for 24 h
      at 25-37  degrees C. Rh_DypB activity is not affected by 1 M NaCl, 10% DMSO, and
      5% Tween-80, i.e., compounds used for dye decolorization or lignin-solubilization
      processes. The enzyme shows broad dye-decolorization activity, especially in the
      presence of Mn2+, oxidizes various aromatic monomers from lignin, and cleaves the
      guaiacylglycerol-beta-guaiacyl ether (GGE), i.e., the Calpha-Cbeta bond of the
      dimeric lignin model molecule of beta-O-4 linkages. Under optimized conditions, 2
      mM GGE was fully cleaved by recombinant Rh_DypB, generating guaiacol in only 10
      min, at a rate of 12.5 MUmol/min mg enzyme.

PMID- 30302520
TI  - Soil acidification amendments change the rhizosphere bacterial community of
      tobacco in a bacterial wilt affected field.
AB  - Application of soil amendments has been wildly used to increase soil pH and
      control bacterial wilt. However, little is known about causal shifts in the
      rhizosphere microbial community of crops, especially when the field naturally
      harbors the disease of bacterial wilt to tobacco for many years due to long-term
      continuous cropping and soil acidification. In this study, biochar (CP), lime
      (LM), oyster shell powder (OS) and no soil amendment additions (Control; CK) were
      assessed for their abilities to improve the soil acidification, change the
      composition of rhizosphere soil bacterial communities and thus control tobacco
      bacterial wilt. The results showed that oyster shell powder significantly
      increased soil pH by 0.77 and reduced the incidence of tobacco bacterial wilt by
      36.67% compared to the control. The Illumina sequencing -based community analysis
      showed that soil amendment applications affected the composition of rhizosphere
      bacterial community and increased the richness and diversity. In contrast, the
      richness and diversity correlated negatively to disease incidence. Using LEfSe
      analyses, 11 taxa were found to be closely related with disease suppression, in
      which Saccharibacteria, Aeromicrobium, and Pseudoxanthomonas could be potential
      indicators of disease suppression. Our results suggested that the suppression of
      bacterial wilt after the application of soil amendments (especially oyster shell
      powder) was attributed to the improved soil pH and increased bacterial richness
      and diversity.

PMID- 30302521
TI  - Alterations in the diversity and composition of mice gut microbiota by lytic or
      temperate gut phage treatment.
AB  - Phages, the most abundant species in the mammalian gut, have numerous advantages
      as biocontrol agent over antibiotics. In this study, mice were orally treated
      with the lytic gut phage PA13076 (group B), the temperate phage BP96115 (group
      C), no phage (group A), or streptomycin (group D) over 31 days. At the end of the
      experiment, fecal microbiota diversity and composition was determined and
      compared using high-throughput sequencing of the V3-V4 hyper-variable region of
      the 16S rRNA gene and virus-like particles (VLPs) were quantified in feces. There
      was high diversity and richness of microbiota in the lytic and temperate gut
      phage-treated mice, with the lytic gut phage causing an increased alpha diversity
      based on the Chao1 index (p < 0.01). However, the streptomycin treatment reduced
      the microbiota diversity and richness (p = 0.0299). Both phage and streptomycin
      treatments reduced the abundance of Bacteroidetes at the phylum level (p < 0.01)
      and increased the abundance of the phylum Firmicutes. Interestingly, two
      beneficial genera, Lactobacillus and Bifidobacterium, were enhanced by treatment
      with the lytic and temperate gut phage. The abundance of the genus
      Escherichia/Shigella was higher in mice after temperate phage administration than
      in the control group (p < 0.01), but lower than in the streptomycin group.
      Moreover, streptomycin treatment increased the abundance of the genera Klebsiella
      and Escherichia/Shigella (p < 0.01). In terms of the gut virome, fecal VLPs did
      not change significantly after phage treatment. This study showed that lytic and
      temperate gut phage treatment modulated the composition and diversity of gut
      microbiota and the lytic gut phage promoted a beneficial gut ecosystem, while the
      temperate phage may promote conditions enabling diseases to occur.

PMID- 30302522
TI  - E. coli Nissle microencapsulation in alginate-chitosan nanoparticles and its
      effect on Campylobacter jejuni in vitro.
AB  - Microencapsulation enhances the oral delivery of probiotic bacteria. In this
      study, the probiotic Escherichia coli Nissle 1917 (EcN) was microencapsulated
      using alginate and chitosan nanoparticles. The result showed 90% encapsulation
      yield of EcN, and the encapsulated EcN displayed significantly (P < 0.05)
      increased survival in low pH (1.5), high bile salt concentration (4%), and high
      temperature (70  degrees C). The most effective cryopreservatives of EcN during
      freezing and thawing was skim milk and sucrose. Exposure to microencapsulated EcN
      significantly (P < 0.05) reduced the Campylobacter jejuni growth by 2 log CFU.
      The rate of EcN release from microcapsule was 9.2 * 105 cell min-1, and the
      appropriate model to describe its release kinetics was zero order. Importantly,
      the entrapment of EcN inside the microcapsule did not eliminate the exterior
      diffusion of EcN produced antioxidant compounds. In addition, the EcN
      microcapsule efficiently adhered to intestinal HT-29 cells and the pre-treatment
      of HT-29 cells with EcN-microcapsule for 4 h significantly (P < 0.05) reduced the
      invasion (1.9 log) of C. jejuni; whereas, completely abolished the intracellular
      survival. Furthermore, HT-29 cells pre-treated with encapsulated EcN in PCR array
      showed decreased expression (> 1.5-fold) of genes encoding chemokines, toll-like
      receptors, interleukins, and tumor necrosis factors. In conclusion, the alginate
      chitosan microcapsule can provide effectual platform to deliver probiotic EcN and
      thereby can reduce the Campylobacter infection in chickens and humans.

PMID- 30302523
TI  - FOXC2 promotes epithelial-mesenchymal transition and cisplatin resistance of non
      small cell lung cancer cells.
AB  - PURPOSE: Platinum-based drugs, particularly cisplatin (DDP), are used in the
      treatment of non-small cell lung cancer (NSCLC). However, development of drug
      resistance remains the major therapeutic barrier in NSCLC. METHODS: The potential
      cisplatin resistance-related genes were identified from the global transcriptomes
      of cisplatin-resistant A549/DDP cells using microarray analysis. Gain- and loss
      of-function assays were performed to analyze the effects of Forkhead Box Protein
      C2 (FOXC2) on the in vitro and in vivo sensitivity of NSCLC cells to cisplatin
      and its possible molecular mechanisms. RESULTS: Using global transcriptome
      analysis, we found that FOXC2 was one of the most upregulated molecules in
      A549/DDP cells compared with A549 cells. We further confirmed that the expression
      of FOXC2 was significantly increased in cisplatin-resistant NSCLC tissues. FOXC2
      knockdown significantly increased the in vitro and in vivo sensitivity of
      A549/DDP cells to cisplatin, whereas overexpression of FOXC2 increased cisplatin
      resistance in cisplatin-sensitive NSCLC cells. Moreover, we found that FOXC2
      promoted cisplatin resistance by induction of epithelial-mesenchymal transition
      (EMT) in NSCLC cells. Furthermore, FOXC2 activated the AKT/GSK3beta signaling
      pathway, and then increased the protein expression of EMT-related transcription
      factor Snail. Inhibition of AKT or knockdown of Snail reversed FOXC2-induced EMT
      and cisplatin resistance of NSCLC cells. CONCLUSION: FOXC2 enhanced cisplatin
      resistance of NSCLC cells through activating AKT/GSK3beta/Snail/EMT signaling
      pathway, which may be a potential novel therapeutic target for overcoming drug
      resistance in human NSCLCs.

PMID- 30302524
TI  - Transcoronary pacing : Reliability during myocardial ischemia and after
      implantation of a coronary stent.
AB  - BACKGROUND: Transcoronary pacing is a useful therapeutic option for the treatment
      of unheralded bradycardias in the setting of percutaneous coronary interventions
      (PCI). OBJECTIVES: In the present study, we investigated the influence of stent
      implantation and transient myocardial ischemia on the feasibility of
      transcoronary pacing in a porcine model. METHODS: 7 adult pigs underwent a
      percutaneous coronary intervention with implantation of a coronary stent under
      general anaesthesia in an animal catheterization laboratory. Transcoronary pacing
      was established by using a standard guidewire isolated with an angioplasty
      balloon positioned in the periphery of the right coronary artery serving as the
      cathode. As the indifferent anode, a skin patch electrode at the back of the
      animal was used. The reliability of transcoronary pacing was assessed by
      measurement of threshold and impedance data and the magnitude of the epicardial
      electrogram at baseline, after implantation of a coronary stent and finally
      during myocardial ischemia. RESULTS: Effective transcoronary pacing could be
      demonstrated in all cases with the standard unipolar transcoronary pacing setup
      yielding a low pacing threshold at baseline of 1.3 +/- 0.8 V with an impedance of
      283 +/- 67 Omega. Implantation of a coronary stent did not influence the pacing
      threshold (1.0 +/- 0.4 V) and impedance (262 +/- 63 Omega). Acute myocardial
      ischemia lead to a significant but clinically nonrelevant increase of the pacing
      threshold to 2.0 +/- 0.6 V and a drop in pacing impedance (137 +/- 39 Omega).
      CONCLUSIONS: Transcoronary pacing in the animal model is not affected by
      implantation of a coronary stent in the same vessel used for pacing. Despite a
      significant increase in pacing threshold, the transcoronary pacing approach is
      reliable in acute myocardial ischemia during a percutaneous coronary
      intervention.

PMID- 30302525
TI  - [Focused echocardiography in acute medicine].
AB  - Focused echocardiography has become increasingly important for bedside
      diagnostics in acute medicine. Focused echocardiography can detect various
      cardiac pathologies, such as pericardial effusion, left ventricular dysfunction,
      right heart strain, relevant heart valve defects and dissection of the ascending
      aorta. Echocardiographic findings should be interpreted in the clinical context.

PMID- 30302526
TI  - [Weaning from dialysis after acute kidney injury in chronically critically ill].
AB  - This study describes the course of renal recovery after dialysis in a specific
      population of chronically critically ill patients with a history of prolonged and
      complicated treatment in an intensive care unit. This study shows that, in a
      specialized center, patients can be successfully weaned from dialysis even months
      after acute kidney injury (AKI). Of the patients who could be recompensated
      (33%), approximately 20% achieved renal recovery more than 3 months after the
      start of dialysis. The duration of renal recovery after AKI did not differ
      between those patients with pre-existing chronic kidney disease (CKD) and those
      without. The reason for dialysis treatment such as sepsis, surgery,
      resuscitation, as well as the risk factors (e. g., diabetes mellitus, arterial
      hypertension, arteriosclerosis) did not reveal a difference in weaning in a
      hazard analysis. As a potential risk factor, only age significantly influenced
      weaning from dialysis in the multivariate hazard model.

PMID- 30302527
TI  - [Hospital-acquired pneumonia].
AB  - Hospital-acquired pneumonia (HAP) is a frequent complication of hospitalisation.
      Due to rising multidrug resistant bacteria an appropriate, empiric and targeted
      therapy is essential and requires an accurate assessment of risk for multidrug
      resistant bacteria. A targeted, temporal therapy is indispensable and should
      begin after a focussed diagnosis. Re-evaluation of therapy is important, as
      clinical course, microbiological and laboratory results might lead to de
      escalation of therapy. In this review article the current German guidelines on
      the diagnosis and therapy of hospital-acquired pneumonia are summarized. Special
      focus is put on targeted, risk-adapted therapy.

PMID- 30302528
TI  - [Point-of-care ultrasonography of the abdomen in emergency and intensive care
      medicine].
AB  - Point-of-care ultrasound is a fundamental part of diagnostic and therapeutic
      management in emergency and intensive care medicine. The availability of high
      resolution mobile ultrasound systems allows high-quality imaging at the bedside
      of the patient. Point-of-care ultrasound is not a comprehensive differential
      diagnostic abdominal ultrasound examination. Rather, the aim of the method is to
      integrate easily detectable sonographic findings into the clinical context. From
      this, the necessary diagnostic or therapeutic procedures are derived. This
      article shows opportunities and limitations of this method. The structure of the
      article is given by the leading clinical symptoms. The focus is on the ultrasound
      examination and the characteristic sonographic findings with illustrative
      ultrasound images. This is followed by a short differential diagnostic
      interpretation. Further diagnostic or therapeutic management is also briefly
      addressed.

PMID- 30302530
TI  - The role of P2Y12 receptor in ischemic stroke of atherosclerotic origin.
AB  - Atherosclerosis is a chronic and progressive disease of the arterial walls and a
      leading cause of non-cardioembolic ischemic stroke. P2Y12 is a well-recognized
      receptor that is expressed on platelets and is a target of thienopyridine-type
      antiplatelet drugs. In the last few decades, P2Y12 receptor inhibitors, such as
      clopidogrel, have been applied for the secondary prevention of non-cardioembolic
      ischemic stroke. Recent clinical studies have suggested that these P2Y12 receptor
      inhibitors may be more effective than other antiplatelet drugs in patients with
      ischemic stroke/transient ischemic attack of atherosclerotic origin. Moreover,
      animal studies have also shown that the P2Y12 receptor may participate in
      atherogenesis by promoting the proliferation and migration of vascular smooth
      muscle cells (VSMCs) and endothelial dysfunction, and affecting inflammatory cell
      activities in addition to amplifying and maintaining ADP-induced platelet
      activation and platelet aggregation. P2Y12 receptor inhibitors may also exert
      neuroprotective effects after ischemic stroke. Thus, P2Y12 receptor inhibitors
      may be a better choice for secondary prevention in patients with atherosclerotic
      ischemic stroke subtypes because of their triple functions (i.e., their anti
      atherosclerotic, anti-platelet aggregation, and neuroprotective activities), and
      the P2Y12 receptor may also serve as a noval therapeutic target for
      atherosclerosis. In this review, we summarize the current knowledge on the P2Y12
      receptor and its key roles in atherosclerosis and ischemic stroke of
      atherosclerotic origin.

PMID- 30302529
TI  - Evolvability of the actin cytoskeleton in oligodendrocytes during central nervous
      system development and aging.
AB  - The organization of actin filaments into a wide range of subcellular structures
      is a defining feature of cell shape and dynamics, important for tissue
      development and homeostasis. Nervous system function requires morphological and
      functional plasticity of neurons and glial cells, which is largely determined by
      the dynamic reorganization of the actin cytoskeleton in response to intrinsic and
      extracellular signals. Oligodendrocytes are specialized glia that extend multiple
      actin-based protrusions to form the multilayered myelin membrane that spirally
      wraps around axons, increasing conduction speed and promoting long-term axonal
      integrity. Myelination is a remarkable biological paradigm in development, and
      maintenance of myelin is essential for a healthy adult nervous system. In this
      review, we discuss how structure and dynamics of the actin cytoskeleton is a
      defining feature of myelinating oligodendrocytes' biology and function. We also
      review "old and new" concepts to reflect on the potential role of the
      cytoskeleton in balancing life and death of myelin membranes and oligodendrocytes
      in the aging central nervous system.

PMID- 30302531
TI  - A-to-I mRNA editing in fungi: occurrence, function, and evolution.
AB  - A-to-I RNA editing is an important post-transcriptional modification that
      converts adenosine (A) to inosine (I) in RNA molecules via hydrolytic
      deamination. Although editing of mRNAs catalyzed by adenosine deaminases acting
      on RNA (ADARs) is an evolutionarily conserved mechanism in metazoans, organisms
      outside the animal kingdom lacking ADAR orthologs were thought to lack A-to-I
      mRNA editing. However, recent discoveries of genome-wide A-to-I mRNA editing
      during the sexual stage of the wheat scab fungus Fusarium graminearum, model
      filamentous fungus Neurospora crassa, Sordaria macrospora, and an early diverging
      filamentous ascomycete Pyronema confluens indicated that A-to-I mRNA editing is
      likely an evolutionarily conserved feature in filamentous ascomycetes. More
      importantly, A-to-I mRNA editing has been demonstrated to play crucial roles in
      different sexual developmental processes and display distinct tissue- or
      development-specific regulation. Contrary to that in animals, the majority of
      fungal RNA editing events are non-synonymous editing, which were shown to be
      generally advantageous and favored by positive selection. Many non-synonymous
      editing sites are conserved among different fungi and have potential functional
      and evolutionary importance. Here, we review the recent findings about the
      occurrence, regulation, function, and evolution of A-to-I mRNA editing in fungi.

PMID- 30302532
TI  - Anti-glomerular basement membrane disease due to monoclonal IgG Lambda
      antibodies: a very rare case of monoclonal gammopathy of renal significance.

PMID- 30302533
TI  - Pre-treatment with Pamidronate Improves Bone Mechanical Properties in Mdx Mice
      Treated with Glucocorticoids.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked disease of progressive muscle
      deterioration and weakness. Patients with DMD have poor bone health which is
      partly due to treatment with glucocorticoids, a standard therapy to prolong
      muscle function that also induces bone loss. Bisphosphonates are used to treat
      adults at risk of glucocorticoid-induced osteoporosis but are not currently used
      in DMD patients until after they sustain fractures. In this study, C57BL/10ScSn
      mdx mice, a commonly used DMD animal model, received continuous glucocorticoid,
      prednisone treatment (0.083 mg/day) from 5 to 10 weeks of age. Pre-treatment with
      the bisphosphonate pamidronate started at 4 weeks of age over a period of 2 weeks
      or 6 weeks (cumulative dose 8 mg/kg for both) to assess the effectiveness of the
      two dosing regimens in ameliorating glucocorticoid-induced bone loss. Mdx mice
      treated with prednisone had improved muscle function that was not changed by
      pamidronate treatment. Glucocorticoid treatment caused cortical bone loss and
      decreased cortical bone strength. Both 2 and 6 week pamidronate treatment
      increased cortical thickness and bone area compared to prednisone-treated Mdx
      mice, however, only 2 week pamidronate treatment improved the strength of
      cortical bone compared to that of glucocorticoid-treated Mdx mice. In the
      trabecular bone, both pamidronate treatments significantly increased the amount
      of bone, and increased the ultimate load but not the energy to fail. These
      results highlight the importance of when and how much bisphosphonate is
      administered prior to glucocorticoid exposure.

PMID- 30302534
TI  - Shallow knee flexion angle during femoral tunnel creation using modified
      transtibial technique can reduce femoral graft bending angle in ACL
      reconstruction.
AB  - PURPOSE: The purpose of this study was to compare femoral graft bending angle
      between patients with femoral tunnel reamed at less than 80 degrees  of knee
      flexion and those with 80 degrees  and above in anatomical anterior cruciate
      ligament (ACL) reconstruction using modified transtibial technique. METHODS:
      Forty-eight patients who underwent ACL reconstruction using bone-patellar-tendon
      bone autograft in modified transtibial technique and CT scan at 1 week
      postoperatively were included in this study. A femoral guidewire insertion into
      aimed femoral position at the medial wall of the femoral lateral condyle was
      started at about 75 degrees  of knee flexion. When the tip of the guidewire was
      blown out into femoral posterior wall, the guidewire was inserted again after
      increasing knee flexion angle. Distance from femoral tunnel exit on the femoral
      lateral cortex-femoral posterior cortex (Distance-E) was measured on
      postoperative lateral radiograph. Femoral and tibial tunnel position was measured
      on 3-D CT images. In addition, femoral graft bending angle was measured on
      reconstructed 2-D CT images. Patients were divided into two groups depending on
      whether femoral tunnel was created at less than 80 degrees  of knee flexion
      (group A) or 80 degrees  or more (group B). RESULTS: There were 32 patients in
      group A and 16 patients in group B, respectively. Average knee flexion angle was
      77.2 degrees  [standard deviation (SD) 1.6] in group A and 83.6 degrees  (SD 2.4)
      in group B, respectively (p < 0.05). Average Distance-E was 5.1 mm (SD 2.6) in
      group A and 6.6 mm (SD 3.8) in group B, respectively. There was no significant
      difference in the femoral and tibial tunnel position between group A and B.
      Femoral graft bending angle was significantly smaller in group A [average angle:
      50.9 degrees  (SD 6.6)] than in group B [average angle: 55.0 degrees  (SD 6.6)]
      (p < 0.05). CONCLUSIONS: Anatomical femoral tunnel was able to be created at less
      than 80 degrees  of knee flexion in two-thirds of patients. Shallower flexion
      angle (less than 80 degrees ) provided gentler femoral graft bending angle
      compared to 80 degrees  or more of knee flexion. Therefore, femoral tunnel
      creation in modified transtibial technique should be started at between 75
      degrees  and 80 degrees  of knee flexion to reduce femoral graft bending angle.
      Shallow knee flexion angle during femoral tunnel creation using modified
      transtibial technique can reduce femoral graft bending angle and may lead to
      better clinical outcomes in ACL reconstruction. LEVELS OF EVIDENCE: Retrospective
      comparative study, Level III.

PMID- 30302535
TI  - [Gaps in the regulatory T cell shield generate immunopathologies].

PMID- 30302537
TI  - [Psychiatric pharmacotherapy of older individuals with severe mental illness].
AB  - BACKGROUND: Chronic schizophrenia, depression, and bipolar disorders, among other
      chronic psychiatric disorders with onset at youth or early adulthood are often
      referred to as severe mental illness (SMI). Aging with SMI is associated with
      various psychosocial, physiological, and medical problems with potential impact
      on psychiatric pharmacotherapy. OBJECTIVES: Determination and discussion of
      problems and special features of the psychopharmacological treatment of older
      persons with SMI and presentation of treatment recommendations for the distinct
      diagnoses. MATERIALS AND METHODS: International literature and guidelines were
      searched. In addition, the basic literature and expert opinions are discussed.
      RESULTS: General problems that influence the psychiatric pharmacotherapy of older
      persons with SMI include nonadherence, nonresponse, polypharmacy, and distinct
      pharmacokinetic changes with aging and somatic comorbidity. Psychotropic drugs
      may exhibit cardiovascular, metabolic, and neuropsychiatric risks, among others.
      The literature regarding effectiveness of psychotropic drugs, drug groups, or
      combination of drugs in older patients with SMI is scarce to nonexistent.
      CONCLUSIONS: Drug treatment of older persons with SMI should be part of an
      overall treatment plan that also has to include social and psychotherapeutic
      components that address the specific problems of this population. Most
      importantly, psychiatric pharmacotherapy should consider these risks and the
      treatment should be tailored to a patient's individual risk profile. Due to a
      general lack of evidence in this special population, treatment strategies of
      standard guidelines should be adjusted with special consideration to
      physiological changes of age.

PMID- 30302536
TI  - Advances in Imaging and Automated Quantification of Malignant Pulmonary Diseases:
      A State-of-the-Art Review.
AB  - Quantitative imaging in lung cancer is a rapidly evolving modality in radiology
      that is changing clinical practice from a qualitative analysis of imaging
      features to a more dynamic, spatial, and phenotypical characterization of
      suspected lesions. Some quantitative parameters, such as the use of 18F-FDG
      PET/CT-derived standard uptake values (SUV), have already been incorporated into
      current practice as it provides important information for diagnosis, staging, and
      treatment response of patients with lung cancer. A growing body of evidence is
      emerging to support the use of quantitative parameters from other modalities. CT
      derived volumetric assessment, CT and MRI lung perfusion scans, and diffusion
      weighted MRI are some of the examples. Software-assisted technologies are the
      future of quantitative analyses in order to decrease intra- and inter-observer
      variability. In the era of "big data", widespread incorporation of radiomics
      (extracting quantitative information from medical images by converting them into
      minable high-dimensional data) will allow medical imaging to surpass its current
      status quo and provide more accurate histological correlations and prognostic
      value in lung cancer. This is a comprehensive review of some of the quantitative
      image methods and computer-aided systems to the diagnosis and follow-up of
      patients with lung cancer.

PMID- 30302538
TI  - Linking structural and effective brain connectivity: structurally informed
      Parametric Empirical Bayes (si-PEB).
AB  - Despite the potential for better understanding functional neuroanatomy, the
      complex relationship between neuroimaging measures of brain structure and
      function has confounded integrative, multimodal analyses of brain connectivity.
      This is particularly true for task-related effective connectivity, which
      describes the causal influences between neuronal populations. Here, we assess
      whether measures of structural connectivity may usefully inform estimates of
      effective connectivity in larger scale brain networks. To this end, we introduce
      an integrative approach, capitalising on two recent statistical advances:
      Parametric Empirical Bayes, which provides group-level estimates of effective
      connectivity, and Bayesian model reduction, which enables rapid comparison of
      competing models. Crucially, we show that structural priors derived from high
      angular resolution diffusion imaging on a dynamic causal model of a 12-region
      network-based on functional MRI data from the same subjects-substantially improve
      model evidence (posterior probability 1.00). This provides definitive evidence
      that structural and effective connectivity depend upon each other in mediating
      distributed, large-scale interactions in the brain. Furthermore, this work offers
      novel perspectives for understanding normal brain architecture and its
      disintegration in clinical conditions.

PMID- 30302539
TI  - Gene expression and neurochemical characterization of the rostromedial tegmental
      nucleus (RMTg) in rats and mice.
AB  - The rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral
      tegmental area (tVTA), is a GABAergic structure identified in 2009 that receives
      strong inputs from the lateral habenula and other sources, sends dense inhibitory
      projections to midbrain dopamine (DA) neurons, and plays increasingly recognized
      roles in aversive learning, addiction, and other motivated behaviors. In general,
      little is known about the genetic identity of these neurons. However, recent work
      has identified the transcription factor FoxP1 as enhanced in the mouse RMTg
      (Lahti et al. in Development 143(3):516-529, 2016). Hence, in the current study,
      we used RNA sequencing to identify genes significantly enhanced in the rat RMTg
      as compared to adjacent VTA, and then examined the detailed distribution of two
      genes in particular, prepronociceptin (Pnoc) and FoxP1. In rats and mice, both
      Pnoc and FoxP1 were expressed at high levels in the RMTg and colocalized strongly
      with previously established RMTg markers. FoxP1 was particularly selective for
      RMTg neurons, as it was absent in most adjacent brain regions. We used these gene
      expression patterns to refine the anatomic characterization of RMTg in rats,
      extend this characterization to mice, and show that optogenetic manipulation of
      RMTg in mice bidirectionally modulates real-time place preference. Hence, RMTg
      neurons in both rats and mice exhibit distinct genetic profiles that correlate
      with their distinct connectivity and function.

PMID- 30302540
TI  - Impact of lumbar hypolordosis on the incidence of symptomatic postoperative
      spinal epidural hematoma after decompression surgery for lumbar spinal canal
      stenosis.
AB  - PURPOSE: Potential associations between radiographic parameters and the incidence
      of symptomatic postoperative spinal epidural hematoma (PSEH) have not been
      identified. This study aimed to identify risk factors including radiographic
      parameters for symptomatic PSEH after posterior decompression surgery for lumbar
      spinal canal stenosis (LSS). METHODS: We retrospectively reviewed 1007
      consecutive patients who underwent lumbar decompression surgery for lumbar spinal
      canal stenosis (LSS) at our institution. We identified 35 cases of symptomatic
      PSEH, defined by clinical symptoms and MRI findings, and selected 3 or 4 age- and
      sex-matched control subjects for each PSEH subject (124 controls). We compared
      radiographic parameters and previously reported risk factors between PSEH and
      control subjects. RESULTS: Compared to the control group, PSEH patients had
      significantly higher preoperative systolic (p = .020) and diastolic (p = .048)
      blood pressure, and more levels of decompression (p = .001). PSEH and control
      subjects had significant differences in lumbar lordosis (PSEH 24.8 degrees  +/-
      14.6 degrees , control 34.8 degrees  +/- 14.5 degrees ), pelvic tilt (25.1
      degrees  +/- 11.7 degrees  vs. 20.8 degrees  +/- 8.4 degrees ), sacral slope
      (23.4 degrees  +/- 9.4 degrees  vs. 27.6 degrees  +/- 8.3 degrees ), and pelvic
      incidence minus lumbar lordosis (23.7 degrees  +/- 15.0 degrees  vs. 13.7 degrees
      +/- 14.6 degrees ). Multivariate analysis revealed two significant risk factors
      for PSEH: decompression of two or more levels and lumbar lordosis < 25 degrees .
      CONCLUSIONS: Multilevel decompression and hypolordosis are significant risk
      factors for symptomatic PSEH after decompression surgery for LSS. LSS patients
      with lumbar hypolordosis or multilevel stenosis should be carefully observed for
      PSEH after decompression surgery. These slides can be retrieved under Electronic
      Supplementary Material.

PMID- 30302541
TI  - Axial loading during MRI reveals deviant characteristics within posterior IVD
      regions between low back pain patients and controls.
AB  - PURPOSE: To investigate differences in functional intervertebral disk (IVD)
      characteristics between low back pain (LBP) patients and controls using T2
      mapping with axial loading during MRI (alMRI). METHODS: In total, 120 IVDs in 24
      LBP patients (mean age 39 years, range 25-69) were examined with T2-mapping
      without loading of the spine (uMRI) and with alMRI (DynaWell(r) loading device)
      and compared with 60 IVDs in 12 controls (mean age 38 years, range 25-63). The
      IVD T2-value was acquired after 20-min loading in five regions of interests
      (ROI), ROI1-5 from anterior to posterior. T2-values were compared between loading
      states and cohorts with adjustment for Pfirrmann grade. RESULTS: In LBP patients,
      mean T2-value of the entire IVD was 64 ms for uMRI and 66 ms for alMRI (p = 0.03)
      and, in controls, 65 ms and 65 ms (p = 0.5). Load-induced T2-differences (alMRI
      uMRI) were seen in all ROIs in both patients (0.001 > p < 0.005) and controls
      (0.0001 > p < 0.03). In patients, alMRI induced an increase in T2-value for ROI1
      3 (23%, 18% and 5%) and a decrease for ROI4 (3%) and ROI5 (24%). More pronounced
      load-induced decrease was detected in ROI4 in controls (9%/p = 0.03), while a
      higher absolute T2-value was found for ROI5 during alMRI in patients (38 ms)
      compared to controls (33 ms) (p = 0.04). CONCLUSION: The alMRI-induced
      differences in T2-value in ROI4 and ROI5 between patients and controls most
      probably indicate biomechanical impairment in the posterior IVD regions. Hence,
      alMRI combined with T2-mapping offers an objective and clinical feasible tool for
      biomechanical IVD characterization that may deepen the knowledge regarding how
      LBP is related to altered IVD matrix composition. These slides can be retrieved
      under Electronic Supplementary Material.

PMID- 30302542
TI  - The effect of training interventions on physical performance, quality of life,
      and fatigue in patients receiving breast cancer treatment: a systematic review.
AB  - OBJECTIVES: The primary purpose of this systematic review is to structure the
      available evidence concerning physical exercise programs and their effects on (1)
      physical performance outcomes, (2) experienced fatigue, and (3) quality of life
      (QoL) in patients during the initial treatment for breast cancer. DATA SOURCES: A
      systematic literature search, based upon the PRISMA guideline, up to January 1,
      2018, was performed using four databases (Web of Science, Cochrane Library for
      Clinical Trials, PubMed, and Medline). STUDY SELECTION: Inclusion criteria were
      as follows: (1) adults > 18 years; (2) patients with breast cancer undergoing
      initial treatment; (3) interventions with the aim to influence the patient's
      physical activity, QoL, or fatigue; (4) randomized controlled trials (RCTs) of
      all ages. The selected studies were scored for methodological quality, and data
      concerning physical performance, QoL, and fatigue were extracted. Twenty-eight
      RCTs were included. DATA EXTRACTION: Different treatment modalities during
      initial treatment were identified (radiation therapy, chemotherapy, and
      combination therapy), as well as different types of physical training
      interventions (cardiovascular endurance exercise, strengthening programs, or a
      combination of both). Therefore, the results were clustered with regard to the
      above-mentioned grouping; extracting every relevant outcome related to physical
      performance (6 MWT or VO2peak; grip/muscle strength), QoL (questionnaires), and
      fatigue (questionnaires). DATA SYNTHESIS: Different training programs (endurance,
      resistance, or a combination of both) were found. These programs were applied
      during different phases of initial treatment. Some programs were supervised while
      others were home based. Overall, most training interventions provided an
      improvement in physical performance and a decrease in perceived fatigue. QoL was
      the outcome variable least susceptible to improvement. CONCLUSION: Different
      types of exercise programs are available for rehabilitation purposes of breast
      cancer patients during adjuvant therapy. Overall resistance training or
      resistance training in combination with CV endurance training provides the best
      results, especially on physical performance and perceived fatigue.

PMID- 30302543
TI  - Correction to: An open-label, randomized, placebo-controlled study on the
      effectiveness of a novel probiotics administration protocol (ProbiotiCKD) in
      patients with mild renal insufficiency (stage 3a of CKD).
AB  - In the original publication of the article, few of the authors were missed in the
      author group.

PMID- 30302544
TI  - Management and evaluation of pregnant women with Takayasu arteritis.
AB  - PURPOSE: To evaluate the clinical characteristics, obstetric/neonatal outcomes,
      and pregnancy complications of pregnant women with Takayasu arteritis (TA).
      METHODS: We retrospectively evaluated the data of 22 pregnancies of 11 patients
      with TA between January 1 2000, and December 31 2017. Patient characteristics,
      severity of disease, obstetric outcomes, pregnancy complications, mode of
      delivery, and neonatal outcomes were evaluated. RESULTS: Based on the
      angiographic classification, four, two, one, three, and one patient were
      classified into groups I, IIa, III, IV, and V, respectively. Based on Ishikawa
      criteria, five, two, two, and two patients were classified into groups 2a, 1, 2b,
      and 3, respectively. Sixteen and five pregnancies resulted in live births and
      spontaneous abortion, respectively. One pregnancy was terminated due to
      prenatally diagnosed trisomy 21. Relapse of TA was observed in five pregnancies.
      Mean age at diagnosis was 24.54 +/- 6.23 years, and mean age at conception was
      30.30 +/- 4.80 years. There were two multiple pregnancies (one twin and one
      triplet) and 19 newborns were delivered alive. Rates of hypertensive disorders of
      pregnancy, preterm birth, intrauterine growth retardation, oligohydramnios, and
      intrauterine fetal demise were 36.4, 18.2, 13.6, 13.6, and 0%, respectively. Mean
      gestational age at birth was 37.25 +/- 2.40 weeks and mean birthweight was
      2682.10 +/- 176.82 g. Median APGAR score was 8. Cesarean section rate was 50%.
      Regional anesthesia/analgesia was administered during 62.5% of the deliveries.
      Ten neonates were admitted to neonatal intensive care unit and eight neonates had
      neonatal respiratory complications. CONCLUSION: Appropriate management of
      pregnant women with TA within the framework of antenatal care programs and
      adopting a multidisciplinary approach are key to ensure successful outcomes.

PMID- 30302545
TI  - Regulation of MMP 2 and MMP 9 expressions modulated by AP-1 (c-jun) in wound
      healing: improving role of Lucilia sericata in diabetic rats.
AB  - AIMS: Lucilia sericata larvae have been successfully used on healing of wounds in
      the diabetics. However, the involvement of the extraction/secretion (ES) products
      of larvae in the treatment of diabetic wounds is still unknown. Activator protein
      1 (AP-1) transcription, composed of c-jun and c-Fos proteins, has been shown to
      be the principal regulator of multiple MMP transcriptions under a variety of
      conditions, also in diabetic wounds. Specifically, MMP-2 and MMP-9's
      transcriptions are known to be modulated by AP-1. c-jun has been demonstrated to
      be a repressor of p53 in immortalized fibroblasts. The aim of the present study
      is to investigate the effects of L. sericata ES on the expression of AP-1 (c
      jun), p53, MMP-2, and MMP-9 in wound biopsies dissected from streptozotocin
      induced diabetic rats. METHODS: The expression levels of MMP-2, MMP-9, c-jun and
      p53 in dermal tissues were determined at days 0, 3, 7 and 14 after wounding,
      using immunohistochemical analysis and quantitative real-time PCR. RESULTS: The
      treatment with ES significantly decreased through inflammation-based induction of
      MMP-2 and MMP-9 expression levels in the wounds of diabetic groups, compared to
      control groups at the third day of wound healing. At the 14th day, there were
      dramatic decreases in expression of c-jun, MMP-9, and p53 in ES-treated groups,
      compared to the diabetic group (P < 0.001, P < 0.05 and P < 0.01, respectively).
      CONCLUSION: ES products of L. sericata may enhance the process of wound healing
      in phases of inflammation, proliferation, and re-epithelization, essentially via
      regulating c-jun expression and modulating MMP-2 and MMP-9 expressions.

PMID- 30302546
TI  - Urachal carcinoma: from gross specimen to morphologic, immunohistochemical, and
      molecular analysis.
AB  - Urachal carcinoma (UrC) is an exceedingly rare neoplasm that develops from the
      urachus, an embryologic remnant of the urogenital sinus and allantois. The most
      commonly encountered histologic subtype is adenocarcinoma. The aim of this study
      is to characterize a series of UrC by morphology, immunohistochemistry, and
      molecular analysis. We retrospectively investigated seven cases of UrCs and
      assessed patient symptoms, imaging, histologic features, immunohistochemical
      profile, molecular characteristics, pathologic stages, and type of treatment.
      Immunostaining for CK7, CK20, Muc-2, CDX2, GATA3, beta-catenin, and CK34betaE12
      was carried out on each neoplasm and on seven non-neoplastic urachal remnants as
      the control group. Additionally, a mutational analysis was performed using the
      QIAact Actionable Insights Tumor Panel Kit, which analyzes KRAS, NRAS, KIT, BRAF,
      PDGFRA, ALK, EGFR, ERBB2, PIK3CA, ERBB3, ESR1, and RAF1. Our cohort comprised
      five females and two males with a mean age of 64 years. UrCs consisted of two
      mucinous cystadenocarcinomas and five invasive, non-cystic adenocarcinomas.
      Carcinoma antigen expression profile was positive for CK20 and negative for
      CK34betaE12 and GATA3 in all cases. Five of seven cases stained positively for
      Muc-2 and CDX2. On the contrary, non-neoplastic urachal remnants were
      immunoreactive for CK34betaE12, CK7, and GATA3. Mutational analysis gave a
      positive result in four out of seven (57.1%) cases. All four positive tumors
      showed RAS mutation and one an additional mutation in PIK3CA. Urachal tumors
      exhibit peculiar morphologic, immunohistochemical, and molecular features. Due to
      the advanced stage at presentation, individualized treatment should be
      undertaken.

PMID- 30302547
TI  - Nanomedicine in cancer stem cell therapy: from fringe to forefront.
AB  - Nanomedicine is the spin-off of modern medicine and nanotechnology and aims to
      prevent and treat diseases using nanoscale materials such as biocompatible
      nanoparticles and nanorobots. Targeted cellular and tissue-specific clinical
      applications with maximal therapeutic effects and insignificant side effects
      could be achieved by the pursuit of nanotechnology in medicine and healthcare
      regimen. The majority of conventional cancer therapies eliminate the cells of the
      tumor but not the cancer stem cells (CSCs). Conversely, the use of nanotechnology
      in CSC-based therapies is an emerging field of biomedical sciences. This article
      summarizes the recent trends and application of nanomedicine especially in CSC
      therapy along with its limitations.

PMID- 30302548
TI  - Novel spiral mapping catheter facilitates observation of the time-to-pulmonary
      vein isolation during cryoballoon ablation.
AB  - Observation of the time-to-pulmonary vein isolation (TTI) by a spiral mapping
      catheter has emerged as a valuable procedural parameter in cryoballoon pulmonary
      vein isolation (PVI). The 1st generation spiral mapping catheter (Achieve, SMC1)
      has been available as an 8-polar catheter with a distal loop diameter of 15 or 20
      mm. The novel spiral mapping catheter (Achieve Advance, SMC2) was designed as a
      true guidewire and is available, in addition to the sizes of the SMC1, as a 10
      polar mapping catheter with a distal loop diameter of 25 mm. Whether these novel
      features of SMC2 influence procedural characteristics of Cryo-PVI in comparison
      to SMC1 has not been reported. In this prospective cohort study 158 patients (age
      65.1 +/- 12.4 years, female 39%, paroxysmal AF 60%) undergoing PVI with the 2nd
      generation cryoballoon were included. SMC1 was used in 57 patients (36%), whereas
      101 patients (64%) underwent Cryo-PVI with the SMC2. All PVs (623/623, 100%) were
      isolated successfully. Mean procedure duration was 72.0 +/- 18.9 min in the SMC1
      group and 74.4 +/- 19.1 min in the SMC2 group (p = 0.432). Mean fluoroscopy time
      was also not different between both study groups (SMC1 15.7 +/- 6.6 min, SMC2
      15.7 +/- 7.3 min, p = 0.593). TTI was observed in 68.6% of pulmonary veins in the
      SMC1 group, whereas TTI observation rate was 82.6% in the SMC2 group (p < 0.001).
      Number of freezes (5.5 +/- 1.5 vs. 6.5 +/- 1.9; p = 0.001) and total freeze
      duration (14.1 +/- 4.5 vs. 17.6 +/- 5.6; p < 0.001) were increased in the SMC2
      group. SMC2 significantly increases TTI observation rate during Cryo-PVI.
      Procedure duration and fluoroscopy time are similar and number of freezes and
      total freeze duration are increased compared to PVI with SMC1 due to decreased
      stability and maneuverability of SMC2.

PMID- 30302549
TI  - Sunflower oil transesterification with methanol using immobilized lipase enzymes.
AB  - The transesterification of sunflower oil with methanol, using immobilized lipase
      enzymes as catalysts, was studied. The process was carried out in a semi
      continuous mode. Temperature (30-50  degrees C), methanol flow (0.024-0.04
      ml/min), kind of enzyme (Lipozyme 62350, Lipozyme TL-IM, Novozym 435 and
      Pseudomonas cepacia Sol-Gel-AK) and enzyme concentrations (1.25-10% by weight)
      were the operating variables. The final product was characterized by the EN 14214
      standard. All the parameters, except for cold filter plugging point, were similar
      to a diesel fuel. For low methanol flows, reaction rate was proportional to
      methanol concentration. High flows caused catalyst deactivation. Novozyme 435,
      Lipozyme TL-IM and Lipozyme 62350 showed similar maximum reaction rates, but
      Novozyme 435 was more resistant to deactivation. Pseudomonas cepacia hardly
      obtained 1% conversion. The catalyst concentration, up to 2.5%, had a positive
      effect on the reaction rate and conversion. The optimum temperature was 40 
      degrees C. The initial reaction rate was in line with the Arrhenius law, up to 50
      degrees C. By differential and integral methods, the Michaelis-Menten,
      competitive inhibition and ping-pong bi-bi kinetic parameters were determined.
      The transesterification of sunflower oil in a semi-continuous regime of alcohol
      improved the results, compared to the discontinuous regime, and those were
      similar to the obtained ones in a discontinuous regime with step-by-step methanol
      addition. The lipase that showed the best yield and higher resistance to
      deactivation was Novozym 435. The kinetic models that forecast the deactivation
      of lipases by an inhibitor described the experimental behavior properly.

PMID- 30302550
TI  - Characterisation of Stramenopile-specific mastigoneme proteins in Phytophthora
      parasitica.
AB  - Mastigonemes, tripartite tubular hairs on the anterior flagellum of Phytophthora
      zoospores, are instrumental for disease dissemination to new host plants. A
      previous study showed that PnMas2 was part of the tubular shaft of Phytophthora
      parasitica mastigonemes. In the current study, genes encoding two related
      proteins, PnMas1 and PnMas3, were identified in the genome of P. parasitica.
      PnMas1 interacts with PnMas2 and also occurs along the mastigoneme shaft. RNA-Seq
      analyses indicate that PnMas1 and PnMas2 genes have similar expression profiles
      both in vitro and in planta but that PnMas3 is expressed temporally prior to
      PnMas1 and PnMas2 during asexual development and plant infection.
      Immunocytochemistry and GFP-tagging document the occurrence of all three PnMas
      proteins within the specialised compartments of the ER during mastigoneme
      formation, but only PnMas1 and PnMas2 occur in mature mastigonemes on the
      flagellar surface. Anti-PnMas1 and anti-PnMas2 antibodies co-labelled two high
      molecular-weight (~400 kDa) protein complexes in native gels but anti-PnMas3
      antibodies labelled a 65 kDa protein complex. Liquid chromatography-mass
      spectrometry analysis identified PnMas1 and PnMas2 but not PnMas3 in flagellar
      extracts. These results suggest that PnMas3 associates with mastigonemes during
      their assembly within the ER but is not part of mature mastigonemes on the
      anterior flagellum. Phylogenetic analyses using homologues of Mas genes from the
      genomes of 28 species of Stramenopiles give evidence of three Mas sub-families,
      namely Mas1, Mas2 and Mas3. BLAST analyses showed that Mas genes only occur in
      flagellate species within the Stramenopile taxon.

PMID- 30302551
TI  - The similarity of crawling mechanisms in aquatic and terrestrial gastropods.
AB  - Crawling gastropods are unique models for studying the functioning of smooth
      muscles and ciliated epithelia, since they cover the foot sole and are involved
      in locomotion, allowing for direct investigation. Two types of crawling are
      known: creeping by muscular waves in terrestrial gastropods such as Helix and
      siliary gliding in aquatic gastropods such as Lymnaea. It was found that the
      smooth muscles that underlie the ciliated epithelium in Lymnaea are involved in
      gliding and contribute significantly to fast crawling. Thus, the locomotor
      apparatus is fundamentally the same in both snails and the difference between
      crawling reflects an adaptation to a habitat. The control of crawling speed is
      also the same. Tonic contraction, relaxation, and rhythmic contractions are
      involved in this control. During a locomotor episode, the sole length and
      crawling speed spontaneously change and directly correlate with each other via
      the contraction force of the muscle cells in the locomotory waves. Dopamine,
      unlike ergometrine, decreases the sole length and crawling speed. Serotonin
      stimulates, increases crawling and determines the number of muscle cells involved
      in the locomotory waves for each locomotor episode. This control (taking into
      account heterogeneity) apparently might exist in any other phasic smooth muscle,
      including vertebrates.

PMID- 30302552
TI  - Experienced trauma team leaders save the lives of multiple-trauma patients with
      severe head injuries.
AB  - The trauma team leader is a professional who receives and treats trauma patients.
      We aimed to evaluate whether or not the seniority of a qualified trauma team
      leader was a prognostic factor for multiple-trauma patients managed by a trauma
      team. This was a retrospective cohort study conducted at a Level I Trauma Center
      in North Taiwan. From January 2009 to December 2013, 284 patients were randomly
      assigned to one of two trauma team leaders (junior and senior leaders) on duty,
      irrespective of the seniority of the qualified trauma team leader. All parameters
      were collected and compared between these two groups. In the subgroup of multiple
      trauma patients with Glasgow Coma Scale (GCS) <= 8, there were significant
      differences in the injury severity score, revised trauma score, and seniority of
      the leader between the alive and dead groups. A multivariate logistic regression
      analysis showed that the seniority of the trauma team leader was an important
      mortality risk factor [odds ratio (OR): 14.529, 95% confidence interval (CI)
      1.683-125.429, p = 0.015] in patients with GCS <= 8. However, in patients with
      GCS > 8, age was the only independent risk factor [OR: 1.055, 95% CI 1.023-1.087,
      p = 0.001]. The seniority of the qualified trauma leader is important for
      teamwork, organization, and efficiency, all of which play an important role in
      improving the survival outcome of patients with GCS <= 8.

PMID- 30302554
TI  - Adhesion-Related Immunomodulatory Activity of the Screened Lactobacillus
      plantarum from Sichuan Pickle.
AB  - Lactic acid bacteria are the majority fermentation starter in the traditional
      fermented foods. In this research, a promising Lactobacillus plantarum was
      isolated from Sichuan pickle and its adhesion properties were analyzed in
      simulated gastrointestinal fluid with different methods. Meanwhile, the
      immunomodulatory effect of this strain was also evaluated in the Caco-2 cells.
      Results found that adhesion-related mub genes and other genes like lsp and tuf
      were upregulated in different culture times. Furthermore, L. plantarum cultured
      at alkaline environment revealed some anti-inflammation activity through
      inhibited expression of cytokine IL-8 and increased expression of anti
      inflammatory cytokine IL-10 in Caco-2 cells. The texture of yogurt after
      fermented by this kind of isolated strain was also investigated, which provides
      the foundation for the further development and application of this kind of strain
      in food production. More investigations need to be carried out to determine
      whether this probiotic contributes to regulation of intestinal flora and
      prevention of gut inflammation.

PMID- 30302553
TI  - A specific allele of MYB14 in grapevine correlates with high stilbene
      inducibility triggered by Al3+ and UV-C radiation.
AB  - KEY MESSAGE: The structural differences of MYB14 promoter in two grapevine
      genotypes affect the expression of MYB14 and stilbene synthesis in response to
      Al3+ and UV-C radiation. Grapevines provide an important fruit crop worldwide,
      but production is often limited by pathogen infection. Stilbenes, a class of
      secondary metabolite, represent phytoalexins that contribute to defence against
      pathogens in many plants, including grapevine. It is known that the transcription
      factors MYB14 and MYB15 are required for the activation of the promoters of
      resveratrol synthase to regulate stilbene biosynthesis. In the current study, we
      observed that stilbene levels were more highly induced by Al3+ and UV-C radiation
      treatments in the cultivar Vitis labrusca 'Concord' than in the cultivar V.
      vinifera 'Cabernet Sauvignon'. We investigated whether genetic/structural
      variations in the MYB14 and MYB15 promoters between these two representative
      genotypes are responsible for the differences in stilbene accumulation.
      Significant differences in the structure and activity of the promoter of MYB14,
      but not MYB15 were identified between the two genotypes, following heterologous
      expression in Nicotiana benthamiana system and treatments with Al3+ and UV-C.
      Hydrogen peroxide (H2O2) was detected in Concord soon after the stress
      treatments, but after diphenyleneiodonium chloride pre-treatment, the expressing
      level of VlMYB14, the promoter activity of VlMYB14 and the accumulation of
      stilbenes was significantly reduced. A model is presented where the induction of
      MYB14 contributes to stilbene accumulation in Concord following Al3+ and UV-C
      treatments involving reactive oxygen species (ROS) production as an early signal.

PMID- 30302555
TI  - Tyrosine-776 of Vip3Aa64 from Bacillus thuringiensis is Important for Retained
      Larvicidal Activity During High-Temperature Storage.
AB  - Vip3Aa (vegetative insecticidal protein) secreted by Bacillus thuringiensis (Bt)
      is highly toxic to lepidopteran insects. The Bt isolate M190 produces Vip3Aa35 at
      high concentrations, and Vip3Aa35 was found to be very effective against
      Spodoptera exigua. Unfortunately, the use of Vip3Aa35 in pest control is limited
      by its short shelf life when stored at high temperatures, retaining activity for
      only 1 month at 37  degrees C. To find a more stable alternative, we screened 500
      isolates of Bt collected from various locations in Thailand and discovered Bt
      isolate 294 which produced large amounts of Vip3Aa64 that exhibited high toxicity
      against S. exigua but could be stored at 37  degrees C for up to 3 months.
      Vip3Aa35 and Vip3Aa64 have only nine amino acid differences between them, with
      six of those residues being located at the C terminus. Vip3Aa35 and Vip3Aa64
      chimeras revealed that the C-terminal sequence is important for the retained
      larvicidal activity observed with Vip3Aa64. Various single amino acid
      substitutions were created to identify the key amino acids responsible for this
      stability. A single residue, Tyr776, was found to be solely responsible, with the
      Vip3Aa35:N776Y acquiring thermostability similar to Vip3Aa64 while the
      Vip3Aa64:Y776N exhibited Vip3Aa35-like thermostability.

PMID- 30302556
TI  - Is ultrasonographic enthesitis evaluation helpful for diagnosis of non
      radiographic axial spondyloarthritis?
AB  - The aim of this study is to evaluate the diagnostic utility of ultrasonographic
      enthesitis assessment in patients with non-radiographic axial spondyloarthritis
      (nr-axSpA) and to compare different sonographic scoring methods. Patients with nr
      axSpA (n = 30) and mechanical back pain (MBP) (n = 30) were enrolled in the study
      with standardized clinical criteria. For both of the groups, a total of 18
      entheses were evaluated in each patient with B mode ultrasound and power Doppler
      by a sonographer who is blinded to initial clinical and radiological assessments.
      Glasgow Ultrasound Enthesitis Scoring System (GUESS), Madrid Sonographic
      Enthesitis Index (MASEI) and D'Agostino grading system were performed. Intra
      rater and inter-rater reliability analyses were evaluated with the intraclass
      correlation coefficient (ICC). There was at least one enthesitis in 96.7% of
      patients with nr-axSpA. Median values of the number of enthesitis were 5 in nr
      axSpA and 0 in MBP. Mean GUESS total scores were 0.9 in MBP and 4.5 in nr-axSpA.
      Mean MASEI total scores were 2.3 and 10.5, respectively. The sensitivities were
      96.7% and 93.3% for GUESS and MASEI while the detected specificities were 80% for
      both methods. For Intra-rater reliability analysis, ICC was calculated as 0.981
      for GUESS and 0.975 for MASEI, while it was calculated as 0.964 and 0.962 for
      inter-rater reliability analysis. Thus, evaluation of enthesitis with ultrasound
      is a reliable, helpful tool for the distinction of patients with nr-axSpA from
      patients with MBP. We favored the use of MASEI because of assessing upper
      extremity, using power Doppler and having a correlation with disease activity.

PMID- 30302557
TI  - Inflammatory reaction, clinical efficacy, and safety of bacterial cellulose wound
      dressing containing silk sericin and polyhexamethylene biguanide for wound
      treatment.
AB  - Bacterial cellulose wound dressings containing silk sericin and PHMB (BCSP) were
      developed in our previous studies. It had good physical properties, efficacy, and
      safety. For further use as a medical material, this dressing was investigated for
      its efficacy and safety in split-thickness skin graft (STSG) donor-site wound
      treatment compared to Bactigras(r) (control). Moreover, the inflammatory
      responses to both dressings were also deeply investigated. For in vivo study,
      expressions of anti-inflammatory cytokines were intensely considered in the
      tissue interfacing area. The result showed that IL-4 and TGF-beta from BCSP
      treated tissue had advantages over Bactigras(r)-treated tissue at 14 and 21 days
      post-implantation. For clinical study, a single-blinded, randomized controlled
      study was generated. The half of STSG donor site wound was randomly assigned to
      cover with BCSP or Bactigras(r). Twenty-one patients with 32 STSG donor site
      wounds were enrolled. The results showed that wound-healing time was not
      significantly different in both dressings. However, wound quality of BCSP was
      better than Bactigras(r) at healing time and after 1 month (p < 0.05). The pain
      scores of BCSP-treated wound were statistically significant lower than
      Bactigras(r)-treated wound (p < 0.05). No sign of infection or adverse event was
      observed after treatment with both dressings. In conclusion, the inflammation
      responses of the dressing were clearly clarified. The advantages of BCSP were
      wound-quality improvement, pain reduction, and infection protection without
      adverse events. It was fit to be used as the alternative treatment of STSG donor
      site wound.

PMID- 30302558
TI  - Ezetimibe in high-risk, previously treated statin patients: a systematic review
      and network meta-analysis of lipid efficacy.
AB  - PURPOSE: While statins are used as first-line treatments for high-risk patients
      with hypercholesterolemia, statin monotherapy is often insufficient to achieve
      target low-density lipoprotein cholesterol (LDL-C) levels. Second-line treatment
      options include up-titration of statin dose, switching to a more potent statin,
      or combination therapy, e.g., with ezetimibe. The aim of this study was to
      evaluate the efficacy of adding ezetimibe to simvastatin, atorvastatin, or
      rosuvastatin monotherapy versus doubling the dosage or switching to a higher
      potency statin in a population of patients with hypocholesterolemia at high risk
      of cardiovascular disease (CVD) and who had been previously treated with a
      statin. METHODS: A systematic literature search was performed and evidence bases
      were established for populations of atorvastatin-, simvastatin-, and rosuvastatin
      experienced patients using eligible randomized controlled trials (RCTs). Based on
      the available data, we constructed networks of evidence and conducted a Bayesian
      network meta-analysis (NMA) within each statin population. The primary outcome of
      interest was percent change from baseline in LDL-C. Changes in total cholesterol
      were explored as a secondary outcome. FINDINGS: Across all patient populations,
      35 RCTs were identified and included in the evidence base. Among patients on
      simvastatin therapy, the addition of ezetimibe resulted in a mean difference (MD)
      in LDL-C of - 13.62% (95% CrI - 19.99, - 6.91; see table below) compared to
      doubling the starting dose of simvastatin. In the population of patients on
      atorvastatin therapy, the addition of ezetimibe resulted in an MD in LDL-C of -
      14.71% (95% CrI - 16.46, - 12.95) compared to doubling the starting dose of
      atorvastatin. The addition of ezetimibe to rosuvastatin resulted in an MD in LDL
      C of - 14.96% (95% CrI - 17.79, - 12.11), compared to doubling the starting
      rosuvastatin dose. Similar trends were observed for changes in total cholesterol.
      IMPLICATIONS: Given the available data, the addition of ezetimibe to ongoing
      simvastatin, atorvastatin, or rosuvastatin monotherapy offers greater reduction
      in LDL-C among patients at high risk of CVD compared to doubling the initial
      statin dose.

PMID- 30302560
TI  - [Opening speech of the Congress President of the German Society for Pathology].

PMID- 30302559
TI  - Correction to: Multidisciplinary approach in the treatment of spinal dural
      arteriovenous fistula-results of endovascular and surgical treatment.
AB  - The author J. Adamkov was incorrectly captured in the original article and is now
      corrected in this article.

PMID- 30302561
TI  - [Report of the working group on thoracic pathology of the German Society of
      Pathology 2018].

PMID- 30302562
TI  - [Systematic analysis of pathological changes in inflammatory dermatoses : New
      dermatopathological criteria and algorithms].
AB  - Standardized analysis of histological findings in a routinely stained section
      without knowledge of the clinical picture ("blind fashion") allows an objective
      assessment of the pathological changes. In inflammatory dermatoses diagnostic
      algorithms and criteria have been proven. They follow defined main inflammatory
      patterns, the composition of the inflammatory infiltrate and additional criteria.
      Taking into account the stage of development and the possibility of collision
      phenomena, this approach will give a histological diagnosis, or at least a
      limited number of differential diagnoses. However, the final diagnosis always
      results from the synopsis of the clinical picture and additional parameters. The
      modern development of algorithms and new histological criteria are outlined in
      autoimmune dermatoses, autoinflammatory syndromes, drug reactions and
      genodermatoses.

PMID- 30302563
TI  - [Amyloid Registry Kiel : An interim balance].
AB  - Amyloid is a pathologic fibrillar aggregation of polypeptides in a cross-beta
      sheet conformation. Amyloidoses are caused by the deposition of amyloid and may
      occur as cerebal and extracerebral diseases. A total of 35 different amyloid
      proteins have been identified. The Amyloid Registry Kiel was founded in 2009 at
      the Department of Pathology of the Christian-Albrechts-University Kiel. It
      currently houses more than 6700 cases of diverse anatomical origin with
      histologically confirmed amyloid and amyloidosis. This large series of cases
      provides unique insights into an otherwise rare disease. This includes the
      validation of novel dyes for the histological recognition and diagnosis of
      amyloid (luminescent conjugated polythiophenes), the in-depth analysis of amyloid
      associated with carpal tunnel syndrome, the distribution pattern of diverse
      amyloids in biopsies of the gastrointestinal tract and the prognostic
      significance of immunoglobulin light chain-derived AL amyloid load in cardiac
      biopsies. Finally, the application of MALDI (matrix-assisted laser
      desorption/ionization) mass spectrometry imaging provided valuable insights into
      the complexity of amyloid deposits, which consist of a diagnostic disease
      specific and amyloid-specific protein/peptide mixture.

PMID- 30302564
TI  - [Reinhard Kandolf : 10 September 1948-31 March 2017].

PMID- 30302565
TI  - Nitrogen-rich core-shell structured particles consisting of carbonized zeolitic
      imidazolate frameworks and reduced graphene oxide for amperometric determination
      of hydrogen peroxide.
AB  - Core-shell structured particles were prepared from carbonized zeolitic
      imidazolate frameworks (ZIFs) and reduced graphene oxide (rGO). The particles
      possess a nitrogen content of up to 10.6%. The loss of nitrogen from the ZIF is
      avoided by utilizing the reduction and agglomeration of graphene oxide with
      suitable size (>2 MUm) during pyrolysis. The resulting carbonized ZIF@rGO
      particles were deposited on a glassy carbon electrode to give an amperometric
      sensor for H2O2, typically operated at a voltage of -0.4 V (vs. Ag/AgCl). The
      sensor has a wide detection range (from 5 * 10-6 to 2 * 10-2 M), a 3.3 MUM (S/N =
      3) detection limit and a 0.272 MUA.MUM-1.cm-2 sensitivity, much higher than that
      of directly carbonized ZIFs. The sensor material was also deposited on a screen
      printed electrode to explore the possibility of application. Graphical abstract
      Nitrogen doped carbon (NC) derived from carbonized zeolitic imidazolate
      frameworks is limited because of low nitrogen content. Here, nitrogen-rich
      NC@reduced graphene oxide (rGO) core-shell structured particles are described.
      The NC@rGO particles show distinctly better H2O2 detection performance than NC.

PMID- 30302566
TI  - Development and validation of a sensitive LC-MS/MS assay for the quantification
      of anserine in human plasma and urine and its application to pharmacokinetic
      study.
AB  - Carnosine (beta-alanyl-L-histidine) and its methylated analogue anserine are
      present in relevant concentrations in the omnivore human diet. Several studies
      reported promising therapeutic potential for carnosine in various rodent models
      of oxidative stress and inflammation-related chronic diseases. Nevertheless, the
      poor serum stability of carnosine in humans makes the translation of rodent
      models hard. Even though anserine and carnosine have similar biochemical
      properties, anserine has better serum stability. Despite this interesting
      profile, the research on anserine is scarce. The aim of this study was to explore
      the bioavailability and stability of synthesized anserine by (1) performing in
      vitro stability experiments in human plasma and molecular modelling studies and
      by (2) evaluating the plasma and urinary pharmacokinetic profile in healthy
      volunteers following different doses of anserine (4-10-20 mg/kg body weight). A
      bio-analytical method for measuring anserine levels was developed and validated
      using liquid chromatography-electrospray mass spectrometry. Both plasma (CMAX:
      0.54-1.10-3.12 uM) and urinary (CMAX: 0.09-0.41-0.72 mg/mg creatinine) anserine
      increased dose-dependently following ingestion of 4-10-20 anserine mg/kg BW,
      respectively. The inter-individual variation in plasma anserine was mainly
      explained by the activity (R2 = 0.75) and content (R2 = 0.77) of the enzyme serum
      carnosinase-1. Compared to carnosine, a lower interaction energy of anserine with
      carnosinase-1 was suggested by molecular modelling studies. Conversely, the two
      dipeptides seems to have similar interaction with the PEPT1 transporter. It can
      be concluded that nutritionally relevant doses of synthesized anserine are well
      absorbed and that its degradation by serum carnosinase-1 is less pronounced
      compared to carnosine. This makes anserine a good candidate as a more stable
      carnosine-analogue to attenuate chronic diseases in humans.

PMID- 30302567
TI  - A needle-like reusable surface-enhanced Raman scattering substrate, and its
      application to the determination of acetamiprid by combining SERS and thin-layer
      chromatography.
AB  - A micro surface-enhanced Raman scattering (SERS) substrate has been fabricated by
      electrochemical deposition of dendrite-like gold on carbon fiber needles (Au
      CFNs). Scanning electron microscopy and energy dispersive spectroscopy were used
      to confirm the presence of the gold nanostructure on the CFNs. This substrate has
      a Raman scattering enhancement factor as high as 3.3 * 10^7 when using rhodamine
      6G as the reporter molecule. The high SERS sensitivity is attributed to the
      massive hotspots on gold bulges that enhance the local surface plasmon resonance.
      The Au-CFN substrate was reproduced 10 times after electrochemically wiping off
      the analytes from the needle-like electrode. The substrate has attractive
      features such as convenient sampling, low sample dosage, and minimal invasion. It
      was applied, in combination with thin-layer chromatography, for the determination
      of acetamiprid on vegetables. The result was more accurate because the sample
      information of both the surface and the bulk can be obtained at the same time
      after inserting the tip of this needle substrate into the TLC plate. The limit of
      detection for acetamiprid is 0.05 MUg?mL-1 and the linear range is 0.1-10 MUg?mL
      1. Graphical abstract A reusable micro needle-like SERS substrate was fabricated
      and applied for pesticide residue analysis. The SERS signal of acetamiprid can be
      acquired on the tip of this micro needle-like Au-CFN substrate. This substrate
      can be reused for 10 times.

PMID- 30302568
TI  - A voltammetric assay for microRNA-25 based on the use of amino-functionalized
      graphene quantum dots and ss- and ds-DNAs as gene probes.
AB  - The authors describe a DNA based voltammetric assay for the cancer biomarker
      microRNA-25. A glassy carbon electrode (GCE) was modified with amino
      functionalized graphene quantum dots and used as an amplifier of electrochemical
      signals. p-Biphenol is introduced as a new electroactive probe with a fairly low
      working potential of 0.3 V (vs. Ag/AgCl). The stages of fabricating the electrode
      were characterized by cyclic voltammetry and electrochemical impedance
      spectroscopy. ss-Probe DNA was immobilized on the modified GCE and then exposed
      to a sample containing microRNA-25. The results indicated that the electrode can
      distinguish complementary microRNA-25 from a single-base mismatch. The increase
      in the electrochemical response of PBP and the positive shift in the potential
      peak indicate that PBP is intercalated between two strands. Under optimized
      experimental conditions, the current of the electrode increases linearly with the
      logarithm of the microRNA-25 concentration in the range from 0.3 nM to 1.0 MUM,
      and the detection limit is 95.0 pM. The assay was successfully employed to the
      determination of microRNA-25 in spiked human plasma. Graphical abstract A novel
      electrochemical nanogenosensor is introduced for simple and sensitive
      determination of microRNA-25, as a biomarker, based on amino-functionalized
      graphene quantum dots (as a surface modifier) and p-biphenol (as an electroactive
      label).

PMID- 30302569
TI  - Ultrasensitive determination of thrombin by using an electrode modified with WSe2
      and gold nanoparticles, aptamer-thrombin-aptamer sandwiching, redox cycling, and
      signal enhancement by alkaline phosphatase.
AB  - A sensitive aptamer/protein binding-triggered sandwich assay for thrombin is
      described. It is based on electrochemical-chemical-chemical redox cycling using a
      glassy carbon electrode (GCE) that was modified with WSe2 and gold nanoparticles
      (AuNPs). The AuNPs are linked to thrombin aptamer 1 via Au-S bonds. Thrombin is
      first captured by aptamer 1 and then sandwiched through the simultaneous
      interaction with AuNPs modified with thrombin-specific aptamer 2 and signalling
      probe. Subsequently, the DNA-linked AuNP hybrids result in the capture of
      streptavidin-conjugated alkaline phosphatase onto the modified GCE through the
      specific affinity reaction for further signal enhancement. As a result, a linear
      range of 0-1 ng mL-1 and a detection limit as low as 190 fg mL-1 are
      accomplished. The specificity for thrombin is excellent. Conceivably, this
      strategy can be easily expanded to other proteins by using the appropriate
      aptamer. Graphical abstract Schematic presentation of an electrochemical
      biosensor for thrombin based on WSe2 and gold nanoparticles, aptamer-thrombin
      aptamer sandwiching, redox cycling, and signal enhancement by alkaline
      phosphatase.

PMID- 30302570
TI  - Density functional theory studies on a non-covalent interaction system: hydrogen
      bonded dimers of zoledronate.
AB  - A computational study was carried out to characterize the hydrogen-bonded dimers
      of Zoledronate (ZOL), which is used widely in treating skeletal diseases. The
      stable conformations, hydrogen bonding interactions, IR spectra, thermodynamic
      properties, and electronic characteristics of nine possible ZOL dimers were
      studied using density functional theory (DFT) at the B3LYP/6-311++G** level. The
      stability of dimers was determined according to the analyses of total electronic
      energies and hydrogen bonding interactions. The results showed that both the
      number and intensity of hydrogen bonds played an important role in determining
      the stability order of dimers, and the hydrogen bonding interactions in dimers
      resulted in a red shift of hydroxyl vibration with a corresponding increase in
      intensity. The calculated thermodynamic properties illustrated that the
      dimerization process can take place spontaneously at room temperature. Natural
      bond orbital and atoms in molecules analyses revealed that the nature of hydrogen
      bonding interactions was attributed to the interactions from lone pair orbital
      n(A) to the antibonding orbital sigma*(D-H), and the interactions were closed
      shell interactions in hydrogen-bonded dimers of ZOL. Graphical abstract Changes
      in Gibbs free energy and infrared spectra of ZL in the dimerization process.

PMID- 30302572
TI  - Pharmacokinetic Considerations with the Use of Antiepileptic Drugs in Patients
      with HIV and Organ Transplants.
AB  - PURPOSE OF REVIEW: Antiepileptic drugs are frequently administered to patients
      with HIV infection or in recipients of organ transplants. The potentially serious
      drug-drug interactions between the "classic" antiepileptic drugs,
      antiretrovirals, and immunosuppressants have been extensively studied. Evidence
      based information on the second and third generation of antiepileptic drugs is
      almost non-existent. The purpose of this review is to analyze the pharmacokinetic
      profile of these newer agents to assess their potential for drug interactions
      with antiretrovirals and immunosuppressants. RECENT FINDINGS: As a group, the
      newer generations of antiepileptic drugs have shown a more favorable drug
      interaction potential compared to the "classic" ones. A group of moderate enzyme
      inducing drugs includes eslicarbazepine acetate, oxcarbazepine, rufinamide, and
      topiramate. These drugs are not as potent inducers as the "classic" drugs but may
      potentially decrease the serum concentrations of some antiretrovirals and
      immunosuppressants. Antiepileptic drugs with no or minimal enzyme-inducing
      properties include brivaracetam, gabapentin, lacosamide, lamotrigine,
      levetiracetam, perampanel, pregabalin, and vigabatrin. The newer generations of
      antiepileptic drugs have expanded the therapeutic options in patients with HIV
      infection or organ transplants.

PMID- 30302571
TI  - Advanced Imaging for Barrett's Esophagus and Early Neoplasia: Surface and
      Subsurface Imaging for Diagnosis and Management.
AB  - PURPOSE OF REVIEW: Esophageal adenocarcinoma bears one of the fastest rising
      incidence of any cancers and generally arises in the setting of gastroesophageal
      reflux and Barrett's esophagus. However, early detection of neoplasia can be
      challenging since most patients are asymptomatic until they progress to more
      advanced and less curable stages, and early dysplastic lesions can be small,
      multifocal, and difficult to detect. Clearly, new imaging tools are needed in
      light of sampling error associated with random biopsies, the current standard of
      practice. RECENT FINDINGS: Advances in endoscopic imaging including virtual
      chromoendoscopy, confocal laser endomicroscopy, and subsurface imaging with
      optical coherence tomography have ushered in a new era for detecting subtle
      neoplastic lesions. Moreover, in light of esophagus-sparing treatments for
      neoplastic lesions, such tools are likely to guide ablation and follow-up
      management. While there is no ideal single imaging modality to facilitate
      improved detection, staging, ablation, and follow-up of patients with dysplastic
      Barrett's esophagus, new advances in available technology, the potential for
      multimodal imaging, and the use of computer-aided diagnosis and biomarkers all
      hold great promise for improving detection and treatment.

PMID- 30302573
TI  - Theoretical investigation of the regioselective ring opening of 2
      methylaziridine. Lewis acid effect.
AB  - The formation of substituted 1,2-diamines via the regiospecific nucleophilic ring
      opening of 2-methylaziridine with methylamine was performed by nucleophilic
      attack at aziridine carbon atoms. A detailed theoretical study was investigated
      by density functional theory (DFT) at the B3LYP level and second order Moller
      Plesset perturbation theory (MP2) by using the 6-311G(d,p) basis set. The third
      Grimme correction term (D3) was used to take into account weak interactions.
      Solvent effects were computed in methanol and dimethylsulfoxide using the
      polarizable continuum model (PCM). Emphasis was placed on the ring opening
      mechanisms of neutral aziridines and aziridinium ions obtained through N
      complexation with the BF3 Lewis acid. Moreover, the effect of substituent groups
      on the regioselectivity of the ring opening was investigated. The nucleophilic
      attack was carried out via two pathways (frontside attack M1 and backside attack
      M2) where activation barriers proved the preference for ring opening through the
      backside attack at the C3 aziridine carbon atom. The obtained results showed that
      the frontside attack with methylamine takes place along a concerted mechanism
      that leads to formation of products through one transition state. However, the
      backside attack is carried via a stepwise process in which the methylamine attack
      takes place in an SN2 fashion where the leaving group is the ring nitrogen. It
      first conduces a ring opening considered as the rate-determining step followed by
      formation of a zwitterionic intermediate. This latter undergoes a rotation to
      allow the proton transfer step and finally leads to formation of the
      thermodynamic products.

PMID- 30302574
TI  - Investigation of ultra-low insertion speeds in an inelastic artificial cochlear
      model using custom-made cochlear implant electrodes.
AB  - PURPOSE: Latest research on cochlear implantations focuses on hearing
      preservation during insertion of the implant's electrode array by reducing
      insertion trauma. One parameter which may influence trauma is insertion speed.
      The objective of this study was to extend the range of examined insertion speeds
      to include ultra-low velocities, being lower than manually feasible, and
      investigate whether these reduce insertion forces. METHODS: 24 custom-made
      cochlear implant test samples were fabricated and inserted into an artificial
      scala tympani model using 12 different insertion speeds while measuring the
      resulting insertion forces. Three commercially available slim straight electrode
      carriers were inserted using the same setup to analyze whether the results are
      comparable. RESULTS: Insertions of the test samples using high insertion speeds
      (2.0/2.8 mm/s) showed significantly higher insertion forces than insertions done
      with low insertion speeds (0.2 mm/s) or ultra-low insertion speeds (< 0.1 mm/s).
      The insertions with commercial slim straight electrode arrays showed
      significantly reduced insertion forces when using a low insertion speed as well.
      CONCLUSIONS: Slow insertions showed significantly reduced insertion forces.
      Insertion speeds which are lower than manually feasible showed even lower
      insertion forces.

PMID- 30302576
TI  - The Prevalence of PTSD Symptoms and Depressive Symptoms and Related Predictors in
      Children and Adolescents 3 Years After the Ya'an Earthquake.
AB  - The objectives of this study were to investigate the prevalence of post-traumatic
      stress disorder (PTSD) symptoms and depressive symptoms in teenage survivors
      three years after the Ya'an earthquake to assess the differences between left
      behind (LBC) and non-left-behind (non-LBC) children, and to explore predictors
      for PTSD symptoms and depressive symptoms. The participants were assessed using
      children's revised impact of event scale (CRIES) and short mood and feelings
      questionnaire (SMFQ), after which t tests, Chi square tests, and a multivariate
      logistic regression were conducted to examine the differences in the LBC and
      identify the associated predictors. It was found that the PTSD and depressive
      symptom prevalences were 13.10% and 20.75%, with the LBC having a significantly
      higher prevalence than the non-LBC. The PTSD and depression symptoms tended to be
      highly comorbid (r = .52, p < .001). Being female, being aged less than 15,
      having siblings, being an LBC, and having higher exposure were found to be
      associated with PTSD and depressive symptoms.

PMID- 30302575
TI  - Association of benign paroxysmal positional vertigo with vitamin D deficiency: a
      systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is an
      idiopathic recurrent inner ear illness that is caused most often by an imbalance
      in the metabolism of calcium carbonate crystals (otoconia) inside the
      semicircular canals, in which the otoconia begin to circulate freely after being
      dislodged from the basic structure. The underlying etiology of this imbalance has
      not yet been well established; however, a few recent articles have revealed that
      vitamin D level abnormality in these patients might play a role. Therefore, we
      conducted the current systematic review analysis to explore potential
      associations of vitamin D level with the occurrence as well as the recurrence of
      BPPV disease. METHODS: A comprehensive literature search was conducted using
      different databases to retrieve all of the articles that have evaluated possible
      associations, irrespective of the study design. Then, we reported different
      vitamin D3 levels from BPPV groups and control groups to estimate the
      standardized mean difference (SMD) between the BPPV and control groups. We also
      calculated the effect size of each study under the random effects statistical
      model. RESULTS: Of the 703 studies that we identified, only 37 studies were found
      to be potential for our analysis, and of these, only seven met our predetermined
      criteria. Two meta-analyses were conducted with respect to the occurrence and the
      recurrence of BPPV. When the BPPV cases were compared to the controls (free of
      BPPV disease), there was an insignificant reduction in vitamin D level among the
      diseased groups (SMD = - 2.20; 95% CI - 6.66 to 2.26). In contrast, when the
      recurrent BPPV groups were compared with the non-recurrent BPPV groups, the
      statistical analysis showed significantly lower level of vitamin D among the
      recurrence BPPV groups (SMD = - 4.47; 95% CI - 7.55 to - 1.29). CONCLUSION:
      Although a negative vitamin D imbalance has been reported among some BPPV
      patients, this review analysis failed to establish a relationship between the
      occurrence of BPPV and low vitamin D level. However, low vitamin D level was
      significantly evident among patients with recurrent episodes of BPPV.

PMID- 30302577
TI  - Enhancing Outcomes of Low-Intensity Parenting Groups Through Sufficient Exemplar
      Training: A Randomized Control Trial.
AB  - Low-intensity parenting groups, such as the Triple P-Positive Parenting Program
      Discussion Groups, appear to be a cost-effective intervention for child conduct
      problems. Several studies evaluating a Triple P Discussion Group on disobedience
      found promising results for improving child and parent outcomes. However, a
      sufficient exemplar training approach that incorporates generalization promotion
      strategies may assist parents to more flexibly apply positive parenting
      principles to a broader range of child target behaviors and settings, leading to
      greater change. We compared the effects of sufficient exemplar training to an
      existing narrowly focused low-intensity intervention. Participants were 78
      families with a 5-8 year-old child. Sufficient exemplar training resulted in more
      robust changes in child behavior and superior outcomes for mothers on measures of
      parenting behavior, parenting self-efficacy, mental health, and perceptions of
      partner support at post-intervention and 6-month follow-up. These results
      indicate that teaching sufficient exemplars may promote generalization leading to
      enhanced intervention outcomes.

PMID- 30302578
TI  - Effective temperature of active fluids and sheared soft glassy materials.
AB  - The dynamics within active fluids, driven by internal activity of the self
      propelled particles, is a subject of intense study in non-equilibrium physics.
      These systems have been explored using simulations, where the motion of a passive
      tracer particle is followed. Similar studies have been carried out for a soft
      glassy material that is driven by shearing its boundaries. In both types of
      systems the non-equilibrium motion have been quantified by defining a set of
      "effective temperatures", using both the tracer particle kinetic energy and the
      fluctuation-dissipation relation. We demonstrate that these effective
      temperatures extracted from the many-body simulations fit analytical expressions
      that are obtained for a single active particle inside a visco-elastic fluid. This
      result provides testable predictions and suggests a unified description for the
      dynamics inside active systems.

PMID- 30302579
TI  - Genotoxic effects of PM10 and PM2.5 bound metals: metal bioaccessibility, free
      radical generation, and role of iron.
AB  - The present study was undertaken to examine the possible genotoxicity of ambient
      particulate matter (PM10 and PM2.5) in Pune city. In both size fractions of PM,
      Fe was found to be the dominant metal by concentration, contributing 22% and 30%
      to the total mass of metals in PM10 and PM2.5, respectively. The speciation of
      soluble Fe in PM10 and PM2.5 was investigated. The average fraction of Fe3+ and
      Fe2+ concentrations in PM2.5 was 80.6% and 19.3%, respectively, while in PM2.5
      this fraction was 71.1% and 29.9%, respectively. The dominance of Fe(III) state
      in both PM fractions facilitates the generation of hydroxyl radicals (.OH), which
      can damage deoxyribose nucleic acid (DNA), as was evident from the gel
      electrophoresis study. The DNA damage by .OH was supported through the in silico
      density functional theory (DFT) method. DFT results showed that C8 site of
      guanine (G)/adenine (A) and C6 site of thymine (T)/cytosine (C) would be
      energetically more favorable for the attack of hydroxyl radicals, when compared
      with the C4 and C5 sites. The non-standard Watson-Crick base pairing models of
      oxidative products of G, A, T and C yield lower-energy conformations than
      canonical dA:dT and dG:dC base pairing. This study may pave the way to understand
      the structural consequences of base-mediated oxidative lesions in DNA and its
      role in human diseases.

PMID- 30302581
TI  - Characterization of the first tenuivirus naturally infecting dicotyledonous
      plants.
AB  - A mechanically transmissible virus tentatively named "melon chlorotic spot virus"
      (MeCSV) was isolated in southeastern France from a melon plant showing chlorotic
      spots and yellowing of the older leaves. Its complete sequence was obtained by
      Illumina and Sanger sequencing. The genome comprises eight RNAs for a total size
      of 20,079 nt and is distantly related to Ramu stunt virus and maize yellow stunt
      virus, two tentative tenuiviruses. MeCSV differs from other tenuiviruses by its
      number of genomic fragments, by being readily mechanically transmissible, and by
      infecting only dicotyledonous hosts. MeCSV should thus be considered a member of
      a tentative new species related to tenuiviruses.

PMID- 30302580
TI  - Shear wave elasticity imaging for residual endoleak and thrombus characterisation
      after endoleak embolisation following endovascular aneurysm repair: a canine
      animal study.
AB  - BACKGROUND: To evaluate residual endoleak and thrombus organisation with shear
      wave imaging (SWI) after endoleak embolisation through an animal study. METHODS:
      This prospective experimental study involved eight dogs with creation of 16 iliac
      aneurysms and type I endoleak after endovascular aneurysm repair (EVAR).
      Embolisation agents were injected into the sac to seal endoleak. SWI and colour
      flow Doppler ultrasound (DUS) were performed at implantation, one week, and one
      and three months after implantation; for three dogs, SWI and DUS were also
      performed six months after implantation. Digital subtraction angiography and
      contrast-enhanced computed tomography were performed at sacrifice. Macroscopic
      and histopathological analyses were processed to identify regions of interest
      (ROIs) for endoleak, fresh thrombus, organised thrombus and embolisation agent,
      where SWI elasticity moduli were compared. RESULTS: At sacrifice, nine aneurysms
      had residual endoleak, while seven were sealed. Ten had a fresh and 15 had an
      organised thrombus. SWI was able to detect all endoleaks, including two cases
      undetected with DUS. Elasticity moduli of 0.2 kPa +/- 0.1 kPa (mean +/- SD), 9.5
      kPa +/- 3.3 kPa, 48.1 kPa +/- 21.3 kPa and 44.9 kPa +/- 23.7 kPa were found in
      the ROIs positioned in endoleaks, fresh thrombi, organised thrombi and
      embolisation agent, respectively. Elasticity values of endoleak and fresh
      thrombus were lower than those of organised thrombi and embolisation agent (p <
      0.001). Stiffness of fresh thrombus at one week (8.7 kPa +/- 3.6 kPa) increased
      at three months (30.2 kPa +/- 13.8 kPa), indicating thrombus maturation (p <
      0.001). CONCLUSIONS: In a dog model of iliac EVAR, SWI was able to identify
      endoleak, thrombus maturation and embolising agents after endoleak embolisation.

PMID- 30302582
TI  - Molecular characterization of H10 subtype avian influenza viruses isolated from
      poultry in Eastern China.
AB  - In recent years, avian-origin H10 influenza viruses have proved capable of
      infecting human beings, and they pose a potential public health threat. Seven H10
      avian influenza viruses (AIVs), H10N3 (n = 2), H10N7 (n = 1), and H10N8 (n = 4),
      were isolated from chickens in Zhejiang Province, Eastern China, during
      surveillance of AIVs in live poultry markets in 2016 and 2017. Phylogenetic
      analysis indicated that Zhejiang H10 strains received gene segments from H10, H3,
      and H7 viruses from birds in East Asia. Animal inoculation tests showed that
      these isolates have low pathogenicity in mice and can replicate in this species.
      Our findings suggest these H10 AIVs have the ability to adapt to chicken or other
      poultry, and highlight the need of long-term surveillance.

PMID- 30302583
TI  - Molecular characterization and analysis of conserved potyviral motifs in bean
      common mosaic virus (BCMV) for RNAi-mediated protection.
AB  - Australian bean common mosaic virus (BCMV) isolates were sequenced, and the
      sequences were compared to global BCMV and bean common mosaic necrosis virus
      (BCMNV) sequences and analysed for conserved potyviral motifs to generate in
      planta RNA-interference (RNAi) resistance. Thirty-nine out of 40 previously
      reported potyvirus motifs were conserved among all 77 BCMV/BCMNV sequences. Two
      RNAi target regions were selected for dsRNA construct design, covering 920 bp of
      the nuclease inclusion b (NIb) protein and 461 bp of the coat protein (CP). In
      silico prediction of the effectiveness of these constructs for broad-spectrum
      defence against the 77 BCMV and BCMNV sequences was done via analysis of putative
      21-nucleotide (nt) and 22-nt small-interfering RNAs (siRNAs) generated from the
      target regions. The effectiveness of both constructs for siRNA generation and
      BCMV RNAi-mediated resistance was validated in Nicotiana benthamiana transient
      assays.

PMID- 30302584
TI  - Development and application of a simple recombinase polymerase amplification
      assay for rapid point-of-care detection of feline herpesvirus type 1.
AB  - Feline herpesvirus type 1 (FHV-1) is a highly contagious pathogen of domestic
      cats and other members of the family Felidae. Point-of-care diagnosis of
      persistent infection in cats is essential for control of its spread. A
      recombinase polymerase amplification (RPA) assay (RPA-LFD-FHV) combined with a
      lateral flow dipstrip (LFD) was developed that uses human body heat for
      incubation. Sensitivity was evaluated by testing a serial dilution of a control
      plasmid, and specificity was evaluated by testing related viruses. Swab samples
      from cats with suspected infection were tested by RPA-LFD-FHV, and the results
      were compared to those obtained by PCR to evaluate its clinical performance. The
      RPA-FLD-FHV assay was carried out successfully within 20 min, using body heat for
      incubation. The RPA-FLD-FHV had a detection limit of 103 copies of the FHV-1 gD
      gene, which was lower than that of PCR, which was 104 copies. The assay could
      detect templates of FHV-1 but not those of other feline and canine viruses.
      Viruses in boiled samples could be efficiently detected by the RPA-FLD-FHV.
      Thirty-one out of the 80 samples were positive by the RPA-FLD-FHV assay, whereas
      only 27 were positive by PCR. DNA sequencing confirmed that the four samples that
      were positive by RPA-FLD-FHV but negative by PCR were indeed positive. These
      results indicate that RPA-FLD-FHV is applicable for clinical use. The RPA-FLD-FHV
      assay is a simple, rapid, and reliable method for point-of-care diagnosis of FHV
      1 infection.

PMID- 30302585
TI  - Correction to: A metagenomic study of the rumen virome in domestic caprids.
AB  - Unfortunately, the original article was online published with error in the
      results section. The error is correction by this erratum.

PMID- 30302586
TI  - Economic viability of anthelmintic treatment in naturally infected beef cattle
      under different nutritional strategies after weaning.
AB  - The aim of the present study was to evaluate the effects of treatment with
      different anthelmintic compounds on the productivity of naturally infected calves
      and the economic viability of these treatments within extensive breeding systems
      employing different nutritional strategies after weaning. For this purpose, 4
      farms with 42-60 calves naturally infected with gastrointestinal nematodes were
      selected. The calves were distributed into 6 groups (7-10 animals each) per farm
      and treated with ivermectin 1%, ivermectin 3.15%, eprinomectin 5%, levamisole
      7.5%, albendazole 15%, and control group (no treatment). These animals were
      evaluated over an experimental period of 150 days. Levamisole 7.5% presented the
      best capacity for the reduction of eggs per gram (EPG) of feces in all herds
      evaluated, followed by albendazole 15% and eprinomectin 5%. Parasite resistance
      to multiple drugs was found in all herds, especially those of Cooperia,
      Haemonchus, Oesophagostomum, and Trichostrongylus. For farm 1, differences in
      weight gain and EPG reduction percentages led to a difference of US$285.06
      between the levamisole and ivermectin 3.15% groups. Similar findings were noted
      for the levamisole and ivermectin 1% groups of farm 3, with a difference of
      US$399.37 because of the final weight gain in these groups. For farms 2 and 4,
      the ivermectin 3.15% and control groups, respectively, were the most profitable;
      these unexpected results were possibly influenced by variables not measured
      during the experimental period. This study suggested that anthelmintic treatments
      should always precede an efficacy test, once they are demonstrated to be most
      profitable under adequate breeding conditions, to ensure adequate control of
      gastrointestinal nematode infection.

PMID- 30302587
TI  - Cercarial dermatitis: a systematic follow-up study of human cases with
      implications for diagnostics.
AB  - Cercarial dermatitis (CD) is an allergic skin disease that rises in consequence
      of infection by invasive stages (cercariae) of trematodes of the family
      Schistosomatidae. CD has been considered a re-emerging disease, human cases have
      been reported from all continents, and tourism-threatening outbreaks occur even
      in frequented recreational areas. Although the symptoms of CD are generally
      known, the data on immune response in human patients are sporadic and
      incomprehensive. In the present study, we attempted to correlate the symptoms,
      personal history, and time course of CD in human patients with differential cell
      counts, dynamics of selected cytokines, and dynamics and quality of antibody
      response. By a systematic follow-up, we obtained a uniquely complex dataset from
      ten persons accidentally and concurrently infected by the same parasite species
      in the same locality. The onset of CD was significantly faster, and the symptoms
      were heavier in participants with a history of CD if compared to naive ones, who,
      however, also developed some of the symptoms. The repeatedly infected persons had
      elevated proportion of eosinophils 1 week post exposure (p.e.) and a stronger
      specific IgG but not IgM response, whereas specific IgE response was not
      observed. Increased serum levels of IL-4 occurred 1 and 3 week(s) p.e. in all
      participants. There was high variability in individual immunoblot patterns of IgG
      response, and no antigen with a universal diagnostic potential was confirmed. The
      presented analyses suggested that a complex approach can improve the accuracy of
      the diagnosis of CD, but component data should be interpreted carefully.

PMID- 30302588
TI  - The prognostic value of tumour-stroma ratio in primary breast cancer with special
      attention to triple-negative tumours: a review.
AB  - PURPOSE: There is a strong need to improve the prognostication of breast cancer
      patients in order to prevent over- and undertreatment, especially when
      considering adjuvant chemotherapy. Tumour stroma characteristics might be
      valuable in predicting disease progression. METHODS: Studies regarding the
      prognostic value of tumour-stroma ratio (TSR) in breast cancer are evaluated.
      RESULTS: A high stromal content is related to a relatively poor prognosis. The
      most pronounced prognostic effect of this parameter seems to be observed in the
      triple-negative breast cancer (TNBC) subtype. CONCLUSIONS: TSR assessment might
      represent a simple, fast and reproducible prognostic factor at no extra costs,
      and could possibly be incorporated into routine pathological diagnostics. Despite
      these advantages, a robust clinical validation of this parameter has yet to be
      established in prospective studies.

PMID- 30302589
TI  - Deep-learning-based detection and segmentation of organs at risk in
      nasopharyngeal carcinoma computed tomographic images for radiotherapy planning.
AB  - OBJECTIVE: Accurate detection and segmentation of organs at risks (OARs) in CT
      image is the key step for efficient planning of radiation therapy for
      nasopharyngeal carcinoma (NPC) treatment. We develop a fully automated deep
      learning-based method (termed organs-at-risk detection and segmentation network
      (ODS net)) on CT images and investigate ODS net performance in automated
      detection and segmentation of OARs. METHODS: The ODS net consists of two
      convolutional neural networks (CNNs). The first CNN proposes organ bounding boxes
      along with their scores, and then a second CNN utilizes the proposed bounding
      boxes to predict segmentation masks for each organ. A total of 185 subjects were
      included in this study for statistical comparison. Sensitivity and specificity
      were performed to determine the performance of the detection and the Dice
      coefficient was used to quantitatively measure the overlap between automated
      segmentation results and manual segmentation. Paired samples t tests and analysis
      of variance were employed for statistical analysis. RESULTS: ODS net provides an
      accurate detection result with a sensitivity of 0.997 to 1 for most organs and a
      specificity of 0.983 to 0.999. Furthermore, segmentation results from ODS net
      correlated strongly with manual segmentation with a Dice coefficient of more than
      0.85 in most organs. A significantly higher Dice coefficient for all organs
      together (p = 0.0003 < 0.01) was obtained in ODS net (0.861 +/- 0.07) than in
      fully convolutional neural network (FCN) (0.8 +/- 0.07). The Dice coefficients of
      each OAR did not differ significantly between different T-staging patients.
      CONCLUSION: The ODS net yielded accurate automated detection and segmentation of
      OARs in CT images and thereby may improve and facilitate radiotherapy planning
      for NPC. KEY POINTS: * A fully automated deep-learning method (ODS net) is
      developed to detect and segment OARs in clinical CT images. * This deep-learning
      based framework produces reliable detection and segmentation results and thus can
      be useful in delineating OARs in NPC radiotherapy planning. * This deep-learning
      based framework delineating a single image requires approximately 30 s, which is
      suitable for clinical workflows.

PMID- 30302590
TI  - An analysis of factors associated with increased fluoroscopy time or the need for
      complex techniques at IVC filter retrieval.
AB  - OBJECTIVES: To evaluate factors associated with increased fluoroscopy time or the
      need for complex techniques at IVC filter retrieval. METHODS: This is a single
      institution retrospective cohort study of 187 consecutive patients who underwent
      IVC filter retrieval. An analysis was performed on associations of patient
      factors with increased fluoroscopy time and/or the need for complex retrieval
      techniques. A complex retrieval was defined as one requiring more than standard
      sheath and snare technique. RESULTS: Access vein during filter placement was not
      associated with filter tilt at placement or removal (p = 0.61 and 0.48). Neither
      the direction of the hook nor its relationship to the tilt was associated with
      the need for complex retrieval or increased retrieval fluoroscopy time (p = 0.25,
      0.23, p = 0.18, 0.23). Tilt angle at placement correlated with hook apposition at
      time of removal (p = 0.01). Hook apposition was associated with complex retrieval
      and increased fluoroscopy time (p < 0.01). Larger tilt angle at placement was not
      associated with complex retrieval (p = 0.22), but a larger angle at removal was
      (p < 0.01). Longer dwell time correlated with the need for complex retrieval (p =
      0.02). Filter type, sex, and age were not associated with complex retrievals (p =
      0.58, p = 0.90, p = 0.99). CONCLUSION: Contrary to previous hypotheses and
      studies, access vein for filter placement did not affect filter tilting, and
      direction of filter hook-tilt relationship did not affect retrieval fluoroscopy
      time or the need for complex retrieval techniques. Increased filter placement
      angle was associated with a larger angle at removal and hook-wall apposition,
      both of which were associated with complex retrievals. KEY POINTS: * Filter hook
      orientation did not correlate with retrieval complexity. * Filter insertion vein
      did not correlate with filter tilt. * Filter tilt and hook apposition to the
      caval wall at the time of retrieval correlated with retrieval procedure
      complexity.

PMID- 30302591
TI  - Preoperative evaluation of small bowel complications in Crohn's disease:
      comparison of diffusion-weighted and contrast-enhanced MR imaging.
AB  - PURPOSE: To compare the accuracy of MR enterography (MRE) using combined T2
      weighted and contrast-enhanced (CE) sequences with that of combined T2- and
      diffusion-weighted (DW) sequences for the detection of complex enteric Crohn's
      disease (CD). MATERIALS: Thirty-eight patients who underwent surgery for CD
      complications and preoperative MRE from 2011 to 2016 were included. MRE
      examinations were blindly analyzed independently by one junior and one senior
      abdominal radiologist for the presence of fistula, stenosis and abscesses. During
      a first reading session, T2-weighted images (WI), steady-state sequences and DW
      MRE were reviewed (set 1). During a separate distant session, T2-WI, True-FISP
      and CE-MRE were reviewed (set 2). Performance of each reader was evaluated by
      comparison with the standard of reference established using intraoperative and
      pathological findings. RESULTS: Forty-eight fistulas, 43 stenoses and 11
      abscesses were found. For the senior radiologist, sensitivity for the detection
      of fistula, stenosis and abscess ranged from 80% to 100% for set 1 and 88% to
      100% for set 2 and specificity ranged from 56% to 70% for set 1 and 53% to 93%
      for set 2, with no significant difference between the sets (p = 0.342-0.429). For
      the junior radiologist, sensitivity ranged from 53% to 63% for set 1 and 64% to
      88% for set 2 and specificity ranged from 0% to 25% for set 1 and 17% to 40% for
      set 2 (p = 0.001 and 0.007, respectively). CONCLUSION: For a senior radiologist,
      DW-MRE has similar sensitivity as CE-MRE for the detection of CD complications.
      For a junior radiologist, CE-MRE yields the best results compared with DW-MRE.
      KEY POINTS: * For experienced readers, DWI has similar diagnostic capability as
      contrast-enhanced MR imaging for the diagnosis of Crohn's disease complications.
      * For senior radiologists, gadolinium chelate injection could be waived for the
      diagnosis of Crohn's disease complications. * The interpretation of DWI for
      Crohn's disease complications requires some experience.

PMID- 30302592
TI  - Lower urinary tract dysfunction in chronic Chagas disease: clinical and
      urodynamic presentation.
AB  - PURPOSE: To describe and give an estimation of the prevalence of urinary
      disorders in chronic Chagas disease, since most clinical research has been
      centered on the description of the cardiac and digestive forms. METHODS: To
      explore this topic, a cross-sectional study was conducted in 137 Bolivian adults
      of both sexes suffering from symptomatic chronic Chagas disease. All patients
      presenting confirmed chagasic cardiomyopathy, megacolon or both underwent a
      urologic symptom questionnaire, uroflowmetry, urinary tract ultrasonography and a
      creatinine assay. When urinary abnormality was detected, a complete urodynamic
      study was proposed including cystometry, pressure-flow studies and urethral
      pressure profile. RESULTS: Out of all study patients, 35 (26%) had a Chagas
      cardiomyopathy, 81 (59%) a megacolon, and 21 (15%) a megacolon associated with
      cardiomyopathy. In all, 63% presented urinary disorders defined by IPSS > 7
      and/or ICIQ SF > 1. Among them, 62% were incontinent, mainly by bladder
      overactivity, and 45% presented grade 2 or 3 renal insufficiency. Of 49 patients,
      the urodynamic study identified 34 patients with detrusor overactivity (69%),
      mostly in those with Chagas megacolon. Median bladder functional capacity,
      urethral closure pressure and bladder compliance had normal values. Moreover, 36%
      of these patients presented moderate hypocontractility, without significant post
      void residual. CONCLUSIONS: This study evidenced lower urinary tract dysfunction
      in a majority of chronic chagasic patients; those presenting megacolon were more
      likely to suffer from urinary incontinence. These results strongly suggest
      including routine urological clinical investigation in chronic Chagas patients,
      as urinary incontinence due to overactive bladder is frequently observed in this
      population.

PMID- 30302593
TI  - Supracostal access tubeless percutaneous nephrolithotomy: minimizing
      complications.
AB  - INTRODUCTION AND OBJECTIVE: Supracostal access in percutaneous nephrolithotomy
      (PCNL) may be avoided due to concern for thoracic complications. The objective of
      the study is to report the safety and efficacy of supracostal access utilizing a
      tubeless (stent only) PCNL technique. PATIENTS AND METHODS: Retrospective review
      of perioperative outcomes of 70 patients (76 renal units) who underwent a
      supracostal tubeless PCNL. No nephrostomy tubes were left. All patients had a 7F
      ureteral stent and Foley catheter placed. The nephrostomy sheath was removed with
      the patient held in end-expiration, and the incision closed. RESULTS: Median
      (IQR) age was 62 (48.3-67) years. Median stone size was 20 * 21 mm, and 14 (18%)
      patients had complete staghorn stones. The upper calyx was the site of access in
      52 (68.4%) cases. Access was above the 12th and 11th rib in 63 (83%) and 12 (16%)
      cases, respectively. Median (IQR) length of stay was 30 (28-32) hours. Fifty
      (68.5%) patients had no residual fragments (< 2 mm) on postoperative imaging.
      Eight (11%) patients underwent an ancillary procedure (7 URS and 1 ESWL), with an
      additional seven patients becoming stone free after this procedure (78%).
      Thoracic complications occurred in two (2.6%) patients: one small pneumothorax,
      and one pleural effusion, both managed conservatively. Other complications
      occurred in nine patients (11.8%): bleeding requiring transfusion (1), fever (4),
      urinary retention (2), and syncope (2). CONCLUSION: Compared to historical
      controls, our approach to upper tract PCNL utilizing a nephrostomy tube-free
      approach resulted in an overall low thoracic complication rate and facilitated
      hospital discharge.

PMID- 30302594
TI  - First ovarian response to gonadotrophin stimulation in rats exposed to neonatal
      androgen excess.
AB  - This study analyzes the effects of neonatal androgenization on follicular growth
      and first ovulation in response to gonadotrophins, using a model of exogenous
      stimulation or the use of subcutaneous ovary grafts in castrated animals to
      replace the hypothalamus-pituitary signal. Neonatal rats (days 1-5) were treated
      with testosterone, dihydrotestosterone or vehicle. At juvenile period, rats were
      stimulated with PMSG, hCG (alone or combined) or used as ovarian donors to be
      grafted on castrated adult female rats. Ovulation and ovarian histology were
      analyzed in both groups. Animals treated with vehicle or dihydrotestosterone
      stimulated with gonadotrophins (pharmacological or by using an ovary graft)
      ovulated, showing a normal histological morphology whereas rats exposed to
      testosterone and injected with the same doses of gonadotrophins did not it. In
      this group, ovulation was reached using a higher dose of hCG. Ovaries in the
      testosterone group were characterized by the presence of follicles with atretic
      appearance and a larger size than those observed in control or
      dihydrotestosterone groups. A similar appearance was observed in testosterone
      ovary grafts although luteinization and some corpora lutea were also identified.
      Our findings suggest that neonatal exposure to aromatizable androgens induces a
      more drastic signalling on the ovarian tissue that those driven by non
      aromatizable androgens in response to gonadotrophins.

PMID- 30302595
TI  - Age of Initial Identification of Autism Spectrum Disorder in a Diverse Urban
      Sample.
AB  - This paper examines age of autism spectrum disorder (ASD) identification and
      related factors in a diverse urban sample, focusing on ASD identification in the
      East African Somali community. The overall average age of initial ASD
      identification was 4.8 years. Somali children received an initial clinical
      diagnosis of Autistic Disorder later than White children, and Somali children
      diagnosed with ASD born outside of Minnesota (MN) received their first
      comprehensive evaluation later than Somali children diagnosed with ASD born in
      MN. Most children had noted developmental concerns before age 3, with no
      significant racial or ethnic differences in those concerns. The current study
      contributes to a limited number of studies on early ASD identification in
      culturally and linguistically diverse populations.

PMID- 30302596
TI  - Melanocyte activation and skin barrier disruption induced in melasma patients
      after 1064 nm Nd:YAG laser treatment.
AB  - Melasma is a frequently acquired hyperpigmentary skin disorder, for which several
      therapies are available. Among them, 1064 nm QS Nd:YAG laser therapy is an
      effective method, but the recurrence rate of laser treatment is still high. The
      aim of the present study was to elucidate the mechanism of the high relapse rate
      of melasma after 1064 nm Nd:YAG laser treatment. Twenty-five female melasma
      patients were treated with 1064 nm Nd:YAG laser for 10 times. The lesional skin
      and non-lesional skin were evaluated by means of a reflectance confocal laser
      scanning microscope before and after laser treatment. Melanin content and
      transepidermal water loss (TEWL) were measured by an MPA9 skin multifunction
      tester accordingly. The melanin index value was significantly decreased in the
      lesional skin after laser treatment, while the non-lesional skin had no
      difference. The dendritic cells were observed at the level of the dermal
      epidermal junction (DEJ) in the lesions of 8 patients before laser treatment,
      while after laser treatment, the dendritic cells were observed in all 25
      subjects. Moreover, there was significant difference between the TEWL value of
      the lesions before and after laser treatment. Furthermore, the TEWL value was
      higher in lesions of the 8 subjects which had dendritic cells compared with other
      17 subjects which had no dendritic cells, no matter before or after laser
      treatment. The relapse patients of melasma had higher TEWL value compared with
      the non-relapse patients. Melanocyte activation and skin barrier disruption may
      be related to the high relapse rate of melasma after laser treatment.

PMID- 30302597
TI  - Dramatic improvement by levodopa treatment in a patient with vascular
      parkinsonism.

PMID- 30302598
TI  - Spatial correlations between MRI-derived wall shear stress and vessel wall
      thickness in the carotid bifurcation.
AB  - BACKGROUND: To explore the possibility of creating three-dimensional (3D)
      estimation models for patient-specific wall thickness (WT) maps using patient
      specific and cohort-averaged WT, wall shear stress (WSS), and vessel diameter
      maps in asymptomatic atherosclerotic carotid bifurcations. METHODS: Twenty
      subjects (aged 75 +/- 6 years [mean +/- standard deviation], eight women)
      underwent a 1.5-T MRI examination. Non-gated 3D phase-contrast gradient-echo
      images and proton density-weighted echo-planar images were retrospectively
      assessed for WSS, diameter estimation, and WT measurements. Spearman's rho and
      scatter plots were used to determine correlations between individual WT, WSS, and
      diameter maps. A bootstrapping technique was used to determine correlations
      between 3D cohort-averaged WT, WSS, and diameter maps. Linear regression between
      the cohort-averaged WT, WSS, and diameter maps was used to predict individual 3D
      WT. RESULTS: Spearman's rho averaged over the subjects was - 0.24 +/- 0.18 (p <
      0.001) and 0.07 +/- 0.28 (p = 0.413) for WT versus WSS and for WT versus diameter
      relations, respectively. Cohort-averaged rho, averaged over 1000 bootstraps, was 
      0.56 (95% confidence interval [- 0.74,- 0.38]) for WT versus WSS and 0.23 (95%
      confidence interval [- 0.06, 0.52]) for WT versus diameter. Scatter plots did not
      reveal relationships between individual WT and WSS or between WT and diameter
      data. Linear relationships between these parameters became apparent after
      averaging over the cohort. Spearman's rho between the original and predicted WT
      maps was 0.21 +/- 0.22 (p < 0.001). CONCLUSIONS: With a combination of
      bootstrapping and cohort-averaging methods, 3D WT maps can be predicted from the
      individual 3D WSS and diameter maps. The methodology may help to elucidate
      pathological processes involving WSS in carotid atherosclerosis.

PMID- 30302599
TI  - Phase I/II study of everolimus combined with mFOLFOX-6 and bevacizumab for first
      line treatment of metastatic colorectal cancer.
AB  - Background This phase I/II trial evaluated toxicity and antitumor activity of
      everolimus plus mFOLFOX6 + bevacizumab for first-line treatment of metastatic
      colorectal cancer (mCRC). Methods A phase I, modified 3 + 3 Fibonacci schema
      determined the maximum tolerated dose (MTD) of everolimus, followed by phase II
      dose expansion. The phase II primary objective was progression-free survival at 6
      months (PFS-6 m). Results The everolimus MTD was 10 mg daily with mFOLFOX6 +
      bevacizumab based on safety from phase I (n = 22). Twenty-five patients were
      treated in the phase II at 10 mg everolimus daily. Frequent grade 3-4 adverse
      events were neutropenia (64%), leukopenia (28%) and hypokalemia (26%). Grade 2
      stomatitis was observed in 62% of patients. Two dose-limiting toxicities were
      observed with one attributed to everolimus 10 mg daily (grade 3 diarrhea,
      hypokalemia, and anorexia) and grade 3 coronary vasospasm attributed to
      fluorouracil. The objective response rate was 53% and was higher (86%) in those
      with PTEN deficiency. PFS-6 m was 96% (95% CI 89-99.9%) at the MTD (n = 35). The
      everolimus recommended phase II dose of this regimen is 7.5 mg daily due to
      frequent stomatitis and dose reductions. Conclusions Everolimus plus mFOLFOX-6 +
      bevacizumab is tolerable and demonstrated preliminary efficacy for first-line
      mCRC. Further studies are warranted in PTEN deficiency.

PMID- 30302600
TI  - Correction to: The Asp99-Arg188 salt bridge of the Pseudomonas aeruginosa HemO is
      critical in allowing conformational flexibility during catalysis.
AB  - In the original publication, fifth author's name was incorrectly published as
      Pierre Moenne-Loccoz.

PMID- 30302601
TI  - DNA binding, cleavage and cytotoxicity studies of three mononuclear Cu(II) chloro
      complexes containing N-S donor Schiff base ligands.
AB  - We report the biological activity of three Cu(II) complexes [Cu(pabt)Cl] (1),
      [Cu(pma)Cl] (2), and [Cu(pdta)Cl]Cl (3) (pabt = N-(2-mercaptophenyl)-2'
      pyridylmethylenimine, pma = N-(2-pyridylmethyl)-2-mercaptoaniline, pdta = 2,2'
      di(pyridyl-2-methyleneimine)diphenyl disulfide). 1-3 display four-line EPR
      multiplet in solution at RT suggesting that these are mononuclear. DNA-binding
      studies using spectrophotometric titration of these complexes with calf thymus
      DNA showed binding through intercalation mode which was found to be consistent
      with the observation of increased viscosity of DNA and quenching of fluorescence
      of ethidium bromide bound DNA in the presence of these complexes. All three
      complexes were found to be efficient in bringing about oxidative and hydrolytic
      cleavage of DNA. The proposed mechanism of hydrolytic DNA cleavage has been
      discussed. MTT assay showed remarkable cytotoxicity on cervical cancer HeLa cell
      line and the IC50 values were 1.27, 4.13, and 3.92 MUM for 1, 2 and 3,
      respectively, as compared to the IC50 value (13 MUM) reported for cisplatin in
      HeLa cells. AO/PI and Annexin-V/PI assay suggest the induction of cell death
      primarily via apoptotic pathway. Nuclear staining using DAPI was used to assess
      changes in nuclear morphology during apoptotic cell death. The role of reactive
      oxygen species (ROS) for induction of apoptotic cell death was studied using
      H2DCF-DA assay and the result suggests that the generation of ROS by the
      complexes may be a possible cause for their antiproliferative activity. TUNEL
      assay showed DNA fragmentation in apoptotic cells. Cell cycle analysis using flow
      cytometry showed significant increase in the G2/M phase in HeLa cells by the
      compounds 1-3. Mononuclear Cu(II) complexes display remarkable cytotoxicity
      against cervical cancer HeLa cell line. The generation of ROS by the complexes
      may be a cause of their antiproliferative activity. Fluorescent images from DAPI
      staining assay revealed that the cells undergoing apoptosis displayed typical
      features like cell shrinkage, membrane blebbing, chromatin condensation and
      nuclear fragmentation. TUNEL assay showed DNA fragmentation in apoptotic cells.

PMID- 30302602
TI  - Comparison of Erich arch bar versus embrasure wires for intraoperative
      intermaxillary fixation in mandibular fractures.
AB  - PURPOSE: Intermaxillary fixation (IMF) is a fundamental principle in the
      management of mandibular fractures but with recent advent of open reduction and
      internal fixation (ORIF), use of IMF is almost limited intraoperatively.
      Therefore, we compared the efficacy of Erich arch bar versus embrasure wires for
      intraoperative IMF in mandibular fractures. METHOD: This prospective study was
      comprised of 50 patients with mandibular fractures who required ORIF with
      intraoperative IMF. Patients were categorized into two groups of 25 patients
      each: Erich arch bar technique was used for group A and embrasure wire technique
      for group B. Parameters were time taken for IMF, needle stick injury, occlusal
      stability, iatrogenic complications, and periodontal status of patients.
      STATISTICAL ANALYSIS: Chi-squared test and unpaired t test analyses was run on
      IBM SPSS 21.0 version (2015) software. RESULT: Mean time for placing embrasure
      wire (3.48 min) was significantly less than that for Erich arch bar (48.08 min).
      Needle stick injury rates to the operator as well as the assistants were
      significantly less when using the embrasure wire than the Erich arch bar. The
      Erich arch bar had significantly superior postoperative occlusion stability.
      Iatrogenic injury was more common when placing the Erich arch bar than the
      embrasure wire. Postoperative oral hygiene status was good in patients that
      received the embrasure wire. CONCLUSION: Embrasure wire technique is a quick,
      easy, and reliable technique for minimally or moderately displaced fractured
      mandible and had better clinical outcomes than did patients that underwent the
      Erich arch bar technique.

PMID- 30302604
TI  - Precision in health care.

PMID- 30302603
TI  - Smoking cessation among men following cancer diagnosis: a matched cohort study.
AB  - PURPOSE: Cigarette smoking among cancer survivors increases the risk of
      recurrence and secondary cancers. We sought to investigate smoking cessation
      following diagnosis of cancer compared to those not diagnosed with cancer. We
      also investigated cessation following diagnosis of a smoking-related and non
      smoking-related cancer separately. METHODS: We conducted a matched cohort study
      within the Health Professionals Follow-Up Study (HPFS). We identified 566 men
      diagnosed with cancer who were current cigarette smokers at the time of diagnosis
      between 1986 and 2010 (exposed). Men diagnosed with cancer were age-matched 1:4
      to men without a diagnosis of cancer who were also current cigarette smokers
      (unexposed). Multivariable conditional logistic regression models were used to
      calculate odds ratios (OR) and 95% confidence intervals (CI) to evaluate the
      association between a cancer diagnosis and smoking cessation within 2 and 4 years
      post diagnosis adjusted for potential confounders, overall and for smoking
      related and non-smoking-related cancers. RESULTS: Of the men with cancer, 38%
      quit within 2 years and 42% within 4 years of diagnosis. Men diagnosed with
      cancer were more likely to quit smoking within 2 (OR = 2.5, 95% CI: 2.0-3.0) and
      4 years (OR = 1.6, 95% CI: 1.3-2.0) post diagnosis, compared to matched men
      without cancer. The association was similar for smoking-related (OR = 3.4, 95%:
      1.6-7.2) and non-smoking-related cancers (OR = 3.8, 95%: 2.8-5.2). CONCLUSIONS:
      Men diagnosed with cancer were more likely to quit smoking compared to men not
      diagnosed with cancer. A cancer diagnosis may be a "teachable moment" in which
      strategies to promote smoking cessation for individuals diagnosed with smoking
      related and non-smoking-related cancers should be investigated. IMPLICATIONS FOR
      CANCER SURVIVORS: There is a continued need for the widespread implementation of
      cessation interventions for cancer survivors.

PMID- 30302605
TI  - Effects of boundary condition on shrinkage vectors of a flowable composite in
      experimental cavity models made of dental substrates.
AB  - OBJECTIVES: Bond strength to enamel and dentin depends on the bonding approach or
      condition. This study investigated the effects of the boundary conditions, in
      terms of the bonding substrate and the bonding condition, on the shrinkage
      vectors of a flowable composite. MATERIALS AND METHODS: An experimental
      cylindrical cavity (diameter = 6 mm, depth = 3 mm) consisting of the enamel floor
      and the surrounding dentin cavity walls was prepared for the "enamel-floor"
      group. Cylindrical cavities of the same dimensions were prepared with access from
      the occlusal enamel into dentin and served as controls. Each cavity model group
      was divided and bonded with two bonding conditions (n = 9): a self-etch (Adper
      Easy Bond, 3M ESPE) and a total-etch approach (OptiBond FL, Kerr). The composite
      (Tetric EvoFlow, Ivoclar Vivadent) was mixed with glass beads, applied to the
      cavity, scanned twice by micro-CT (uncured and cured states). The scans were
      evaluated by rigid registration, sphere segmentation, and registration for
      computing shrinkage vectors. RESULTS: The free surface of all restorations moved
      downward. The shrinkage vectors in the experimental cavity model pointed downward
      towards the enamel cavity floor, and the net axial movement was downward. In the
      control group, shrinkage vectors additionally moved upward, away from the cavity
      floor. The effect of the bonding substrate and the bonding condition was
      investigated for the shrinkage vectors and the axial movement (univariate ANOVA).
      CONCLUSION: The bonding substrate, enamel, influenced the shrinkage vectors'
      direction, while the bonding condition caused only variations in the magnitude.
      CLINICAL RELEVANCE: Bonding to enamel influences shrinkage vectors' direction,
      while the bonding condition plays only a minor role. Graphical abstract ?.

PMID- 30302606
TI  - Alveolar bone preservation by a hydroxyapatite/collagen composite material after
      tooth extraction.
AB  - OBJECTIVE: The aim of this study was to assess the effectiveness of a
      hydroxyapatite/collagen composite material (HAp/Col) for preservation of alveolar
      bone after tooth extraction. MATERIALS AND METHODS: HAp/Col was applied to the
      alveolus bone ridge preservation after tooth extraction, because of subsequent
      dental implant placement in 35 regions of 24 patients (mean age, 59.3 years;
      range, 25-81 years). Cone beam computed tomography was used to assess changes in
      alveolar bone at the extraction site before and at 3 months (mean, 13.7 weeks;
      range, 10-17 weeks) after tooth extraction. Changes in height and width of the
      alveolar bone were measured to evaluate bone reduction after surgery. Bone biopsy
      was performed at 11 regions of dental implant placement to observe bone
      regeneration and remaining material in the extraction socket. RESULTS: The
      alveolar bone height was decreased by 0.00 +/- 2.44 mm at the buccal side and
      0.35 +/- 1.73 mm at the lingual side, while the width was decreased by 1.02 +/-
      1.64 mm at 3 months after surgery. The middle of the socket floor was elevated by
      5.71 +/- 3.45 mm at 3 months after surgery. Bone biopsy specimens revealed no
      remaining implanted material, and approximately 49.79 +/- 14.41% of the specimens
      were occupied by bone tissue. CONCLUSIONS: According to the result of this study,
      HAp/Col is a reliable material to presearve alveolar bone after tooth extraction.
      CLINICAL RELEVANCE: HAp/Col contributes dental implant treatment due to maintain
      the alveolar bone after tooth extraction.

PMID- 30302607
TI  - Comparative evaluation of autofluorescence imaging and histopathological
      investigation for oral potentially malignant disorders in Taiwan.
AB  - OBJECTIVES: Autofluorescence imaging is gaining popularity as an adjunctive test
      for oral potentially malignant disorders (OPMD). This study evaluated the
      efficacy of autofluorescence imaging based on the current standard oral mucosal
      disorder checklist in Taiwan. MATERIALS AND METHODS: In total, 126 patients
      suspected to have mucosal disorders at the Division of Oral and Maxillofacial
      Surgery, Tri-Service General Hospital, Taipei, Taiwan, were enrolled. Following a
      conventional oral examination by using the oral mucosal disorder checklist and an
      autofluorescence imaging examination, all participants underwent
      histopathological examination to access epithelial dysplasia. RESULTS: Among 126
      patients, 68 patients were diagnosis as having an OPMD and 63 having epithelial
      dysplasia. Autofluorescence imaging exhibited a sensitivity, specificity,
      positivity predictive value (PPV), negative predictive value (NPV), and accuracy
      of 77.94%, 35.42%, 63.10%, 53.13%, and 60.34%, respectively, for OPMD and of
      88.89%, 43.86%, 63.64%, 78.13%, and 67.50%, respectively, for epithelial
      dysplasia. After the exclusion of 48 non-OPMD cases according to the checklist,
      the sensitivity, specificity, PPV, NPV, and accuracy of autofluorescence imaging
      became 87.50%, 72.73%, 94.23%, 53.33%, and 85.07%, respectively, for epithelial
      dysplasia. CONCLUSION: The efficacy of epithelial dysplasia identification and
      OPMD risk assessment can be increased after the exclusion of the non-OPMD cases
      through autofluorescence imaging. CLINICAL RELEVANCE: Autofluorescence imaging is
      a useful adjunct that can assist specialists in assessing OPMD patients prone to
      dysplasia without compromising patient care.

PMID- 30302608
TI  - Yes-associated protein (YAP) molecule expression in odontogenic epithelium of
      ameloblastoma.
AB  - OBJECTIVES: YAP (Yes-associated protein molecule) augments multiple processes
      known to be important for tumor progression and metastasis. Hence, the
      application of YAP as a targeted therapy for several malignancies has been
      documented in the literature. Ameloblastoma being a locally invasive odontogenic
      lesion causes tissue destruction and presents with a great chance of recurrence.
      Based on these qualities, we hypothesized that YAP could exhibit increased
      expression in the odontogenic epithelium of ameloblastoma. Therefore, the
      objective of the present study was to evaluate the immunohistochemical expression
      of YAP in ameloblastoma and compare the immunoreactivity of YAP in ameloblastoma
      and dental follicle. MATERIALS AND METHODS: Twenty-four paraffin-embedded tissue
      blocks of ameloblastoma and dental follicle each were retrieved from the
      departmental archives. Immunohistochemical (IHC) staining was performed employing
      YAP antibody on 5-MUm thick sections. The expression of YAP was reviewed on the
      peripheral lining of ameloblast-like cells and centrally placed stellate
      reticulum-like cells and was further graded as negative, weak, or strong. For
      data analysis, Chi-square test and Fisher's exact test were applied. RESULTS: In
      ameloblastoma, peripheral/basal cells exhibited strong expression for YAP in
      12/24 cases and weak expression in the other 12 cases. Whereas, 20 cases of
      dental follicle presented negative expression and only four cases exhibited weak
      expression (p < 0.001). On statistical analysis, the differences in expression of
      YAP in stellate cells of ameloblastoma and dental follicle were found to be
      significant (p < 0.001). CONCLUSION: YAP expression was strongly seen in
      ameloblastoma as compared to the epithelial islands of dental follicle. The
      neoplastic nature of ameloblastoma could be attributed to YAP molecule and it may
      play a possible role in tumor invasiveness. CLINICAL RELEVANCE: Positive YAP
      expression in ameloblastoma and negative expression in the odontogenic epithelial
      islands of dental follicle insinuate that YAP could be responsible for the
      aggressiveness and local tissue invasion commonly encountered with ameloblastoma.

PMID- 30302609
TI  - Presentation of gaps around endodontic access cavity restoration by phase
      contrast-enhanced micro-CT.
AB  - OBJECTIVE: To evaluate the feasibility of synchrotron-based phase-contrast (PC)
      MUCT for visualization of the gaps and differentiation between the gaps,
      restorative, and endodontic materials at the tooth-restoration interface.
      MATERIALS AND METHODS: Standardized access cavities were prepared in human
      maxillary molars and subjected to materials, simulating endodontic treatment: (1)
      saline irrigation; (2) NaOCl and 17% EDTA irrigation; (3) same as group 2,
      followed by application of Ca(OH)2; and (4) same as group 2, followed by
      application of root canal sealer. The access cavities were cleaned and restored
      using an etch-and-rinse adhesive and a composite material in multilayering
      technique. The samples were thermocycled (1000 cycles, 5-55  degrees C).
      Synchrotron-based MUCT imaging was performed obtaining absorption and PC MUCT
      images before and after the immersion of the samples into 50% AgNO3. PC MUCT
      images were compared to absorption MUCT and conventional optical microscopy
      images. RESULTS: PC MUCT of unstained samples enabled the best visualization of
      gaps and differentiation of restorative and endodontic materials, contaminating
      the cavity surface. PC MUCT revealed that AgNO3 staining leads to an
      overestimation of gap size due to anterograde and retrograde AgNO3 infiltration
      into dentinal tubules and underestimation of large gaps due to lack of AgNO3
      penetration. CONCLUSION: Synchrotron PC MUCT imaging enables better visualization
      of gap and differentiation of materials at the tooth-restoration interface. MUCT
      imaging with AgNO3 staining has shown certain over- and underestimations. Future
      research should be aimed at incorporating PC MUCT imaging of unstained samples
      for the validation of results obtained with other methods. CLINICAL SIGNIFICANCE:
      Contamination of cavity walls with an endodontic sealer or Ca(OH)2 leads to
      increased gap formation at the tooth-restoration interface.

PMID- 30302610
TI  - Comparing the outcomes of gold-standard dental examinations with photographic
      screening by mid-level dental providers.
AB  - OBJECTIVES: To determine the detectability of the intra-oral photographic method
      in comparison to the baseline, comprehensive dental examination (CDE), in
      children when performed by different levels of dental practitioners. MATERIALS
      AND METHODS: As part of a quality assurance program, intra-oral photographs were
      obtained from 77 patients (2-18 years) as part of a CDE before undertaking dental
      treatment under general anaesthesia. A DSLR camera was utilised to acquire images
      which were subsequently uploaded to a cloud-based server. The baseline for each
      participant was established during the CDE, utilising both visual and
      radiographic examination, which was then compared to the assessment made by a mid
      level dental practitioners (MLDP). The evaluation was based on utilising an
      odontogram where the teeth were charted either as decayed or filled. RESULTS:
      Specificity (95%) was higher than sensitivity (61.5%) when comparing the
      photographic assessment with the benchmark CDE assessment. The inter-rater
      reliability between the two methods of assessment was substantial, with a kappa
      score of 0.62. The photographic assessment method underestimated the decayed and
      filled teeth, as observed by the caries experience (dft/DFT scores) (CDE = 7.01
      vs. photographic assessment = 5.22). There were lower levels of diagnostic
      detection in the posterior teeth as compared to the anterior teeth assessments.
      CONCLUSIONS: Although the CDE is still considered to be the gold-standard, this
      study found that the photographic caries assessment by MLDP produced an
      acceptable diagnostic level of detection particularly for the anterior teeth.
      CLINICAL RELEVANCE: The photographic method could offer a potential cost-saving
      and user-friendly screening.

PMID- 30302611
TI  - Bone repair in craniofacial defects treated with different doses of alendronate:
      a histological, histomorphometric, and immunohistochemical study.
AB  - OBJECTIVE: The objective of the study is to evaluate bone repair in rats treated
      with different alendronate doses. MATHERIALS AND METHODS: Sixty female rats
      ovariectomized were randomly divided in three groups: group C (control group),
      group A1 (ALN/1 mg/kg), and A2 (ALN/ 3 mg/kg). Each animal received subcutaneous
      applications of sodium alendronate at a dose correspondent to group A1 or A2
      three times a week, while the control group received 0.9% saline solution. After
      4 weeks of application, a critical defect was created in the calvaria of animals
      of all groups. The defect was filled by particulate autogenous bone. The
      applications were maintained until euthanasia, which occurred 15 and 60 days
      after the surgical procedure. The pieces were sent for histological,
      histomorphometric and immunohistochemical analysis. The data were submitted to
      statistical analysis with significance level of 0.05. RESULTS: The descriptive
      histological analysis demonstrated an increase in bone neoformation in both
      groups treated with alendronate when compared to the control group. The
      histomorphometric analysis showed an increase in the amount of neoformed bone in
      A1 and A2 groups when compared to group C, both at 15 days (p = 0.0002) and at 60
      days (p = 0.001). In the immunohistochemical analysis, it was possible to observe
      a difference in immunolabeling just for Mmp2 at the time of 60 days in A1 (p =
      0.001) and A2 (p = 0.023) when compared to the control group. CONCLUSION:
      Systemic delivery of alendronate, regardless of the dose, increased the amount of
      bone neoformation. CLINICAL RELEVANCE: Prescription of sodium alendronate at 1
      mg/kg for improvement of bone neoformation in bone graft procedures.

PMID- 30302612
TI  - Effect of sucralfate against hydrochloric acid-induced dental erosion.
AB  - OBJECTIVE: Devising effective measures for the prevention of hydrochloric acid
      (HCl)-induced erosion is of great significance. This is even more important in
      dentine, in which products have limited diffusion. Therefore, agents that can
      bind to proteins forming an acid-resistant gel-like coat, such as sucralfate, may
      stand out as a promising alternative. This study investigated the protective
      effect of sucralfate suspensions against HCl-induced dental erosion. MATERIALS
      AND METHODS: In the first experiment, hydroxyapatite (HAp) crystals were pre
      treated with a commercial sucralfate suspension (CoSS, pH 5.9), a stannous
      containing sodium fluoride solution (NaF/SnCl2 pH 4.5), two prepared sucralfate
      suspensions (PrSS, pH 5.9 and 4.5), or deionized water (DI, control). HAp
      dissolution was measured using a pH-stat system. In a subsequent experiment,
      embedded/polished enamel and root dentine slabs were allocated into five groups
      to be treated with one of the tested substances prior to and during erosion
      remineralization cycles (HCl-2 min + artificial saliva 60 min, two times per day,
      5 days). Surface loss was assessed profilometrically. Data were analyzed by ANOVA
      and Tukey's tests. RESULTS: HAp dissolution was as follows: NaF/SnCl2 < CoSS <
      PrSS/pH 4.5, while PrSS/pH 5.9 = DI and both did not differ from CoSS and PrSS/pH
      4.5. In enamel, surface loss did not differ between CoSS and PrSS/pH 4.5, with
      both having lower surface loss than PrSS/pH 5.9 and DI and NaF/SnCl2 differing
      only from DI. In root dentine, surface loss was as follows: CoSS < PrSS/pH 5.9 <
      (NaF/SnCl2 = DI), while PrSS/pH 4.5 = CoSS = PrSS/pH 5.9. CONCLUSION: Sucralfate
      suspension provided anti-erosive protection to HCl-induced erosion. CLINICAL
      RELEVANCE: Sucralfate may protect teeth against erosion caused by gastric acid.

PMID- 30302614
TI  - Assembly and Trafficking of Homomeric and Heteromeric Kainate Receptors with
      Impaired Ligand Binding Sites.
AB  - Kainate receptors (KARs) are a subfamily of ionotropic glutamate receptors
      (iGluRs) mediating excitatory synaptic transmission. Cell surface expressed KARs
      modulate the excitability of neuronal networks. The transfer of iGluRs from the
      endoplasmic reticulum (ER) to the cell surface requires occupation of the agonist
      binding sites. Here we used molecular modelling to produce a range of ligand
      binding domain (LBD) point mutants of GluK1-3 KAR subunits with and without
      altered agonist efficacy to further investigate the role of glutamate binding in
      surface trafficking and activation of homomeric and heteromeric KARs using
      endoglycosidase digestion, cell surface biotinylation and imaging of changes in
      intracellular Ca2+ concentration [Ca2+]i. Mutations of conserved amino acid
      residues in the LBD that disrupt agonist binding to GluK1-3 (GluK1-T675V, GluK2
      A487L, GluK2-T659V and GluK3-T661V) reduced both the total expression levels and
      cell surface delivery of all of these mutant subunits compared to the
      corresponding wild type in transiently transfected human embryonic kidney 293
      (HEK293) cells. In contrast, the exchange of non-conserved residues in the LBD
      that convert antagonist selectivity of GluK1-3 (GluK1-T503A, GluK2-A487T, GluK3
      T489A, GluK1-N705S/S706N, GluK2-S689N/N690S, GluK3-N691S) did not alter the
      biosynthesis and trafficking of subunit proteins. Co-assembly of mutant GluK2
      with an impaired LBD and wild type GluK5 subunits enables the cell surface
      expression of both subunits. However, [Ca2+]i imaging indicates that the
      occupancy of both GluK2 and GluK5 LBDs is required for the full activation of
      GluK2/GluK5 heteromeric KAR channels.

PMID- 30302613
TI  - Trans-cinnamaldehyde Modulates Hippocampal Nrf2 Factor and Inhibits Amyloid Beta
      Aggregation in LPS-Induced Neuroinflammation Mouse Model.
AB  - Trans-cinnamaldehyde (CNM) has recently drawn attention due to its potent anti
      inflammatory and antioxidant properties. The current study explored the memory
      enhancing effects of CNM against lipopolysaccharide (LPS)-induced
      neuroinflammation in mice. CNM and curcumin (a reference antioxidant) were
      administered at a dose of 50 mg/kg i.p. 3 h after a single LPS injection (0.8
      mg/kg, i.p.) and continued daily for 7 days. Our results displayed that CNM and
      curcumin significantly ameliorated the LPS-induced impairment of learning and
      memory, neuroinflammation, oxidative stress and neuronal apoptosis. Memory
      functions and locomotor activity were assessed by Morris water maze, object
      recognition test and open field test. Both CNM and curcumin activated the nuclear
      factor erythroid 2 related factor 2 (Nrf2) and restored levels of downstream
      antioxidant enzymes superoxide dismutase and glutathione-S-transferase (GST) in
      the hippocampus. They also attenuated LPS-induced increase in hippocampal
      contents of interleukin-1beta (IL-1beta), malondialdehyde and caspase-3.
      Immunohistochemistry results showed that both CNM and curcumin reduced Abeta1-42
      protein accumulation in brain of mice. Remarkably CNM's effect on IL-1beta was
      less pronounced than curcumin; however it showed higher GST activity and more
      potent anti-apoptotic and anti-amylodogenic effect. We conclude that, CNM
      produces its memory enhancing effects through modulation of Nrf2 antioxidant
      defense in hippocampus, inhibition of neuroinflammation, apoptosis and amyloid
      protein burden.

PMID- 30302615
TI  - Field grown transgenic Pm3e wheat lines show powdery mildew resistance and no
      fitness costs associated with high transgene expression.
AB  - Pm3 from wheat encodes a nucleotide-binding leucine-rich repeat type of receptor
      and confers resistance to powdery mildew caused by the fungal pathogen Blumeria
      graminis f.sp. tritici (Bgt). Each of the 17 functional Pm3 alleles identified so
      far confers resistance to a distinct spectrum of Bgt isolates. Variant Pm3e has
      been found in wheat donor line W150 and differs only by two amino acids from the
      non-functional variant Pm3CS. In order to evaluate the capability of Pm3e to
      provide powdery mildew field resistance, we generated transgenic Pm3e lines by
      biolistic transformation of the powdery mildew susceptible spring wheat cultivar
      Bobwhite. Field trials conducted during four field seasons in Switzerland showed
      significant and strong powdery mildew resistance of the Pm3e transgenic lines,
      whereas the corresponding biological sister lines, not containing the transgene,
      were severely powdery mildew infected. Thus Pm3e alone is responsible for the
      strong resistance phenotype. The field grown transgenic lines showed high
      transgene expression and Pm3e protein accumulation with no fitness costs on plant
      development and yield associated with Pm3e abundance. Line E#1 as well as sister
      line E#1 showed delayed flowering due to somaclonal variation. The study shows
      the capability of Pm3e in providing strong powdery mildew field resistance,
      making its use in wheat breeding programs very promising.

PMID- 30302616
TI  - Chick embryonic cells as a source for generating in vitro model of muscle cell
      dystrophy.
AB  - Chick embryonic cells can be used to develop an easy and economical in vitro
      model for conducting studies on the disease muscle dystrophy (MD). For this, the
      limb myoblasts from 11th day chick embryo were isolated and cultured. To this
      muscle cell culture, anti-dystroglycan antibody (IIH6) was added so as to target
      the alpha-dystroglycan and disrupt the connection between the cytoskeletal
      proteins and the extracellular matrix (which is a characteristic feature of MD).
      Cells were allowed to differentiate further and the morphometrics and mRNA
      expression were studied. The IIH6-treated muscle cells displayed changes in
      morphometry, contractibility, and also atrophy was observed when compared to the
      control cultures. Concomitant gene expression studies showed an upregulation in
      TGF-beta expression, while the muscle sculpture genes MYOD1, MYF5, LAMA2 and MYOG
      were downregulated resembling the MD in vivo. This simple and cost-effective
      method can be useful in studies to further understand the disease mechanism and
      also in conducting initial studies on effect of novel pharmacological agents.

PMID- 30302617
TI  - Role of PI3K-Akt and MAPK Signaling in Uranyl Nitrate-Induced Nephrotoxicity.
AB  - Uranium is a heavy metal of considerable environmental and occupational concern.
      It is well-known that the kidney is the major target organ of uranium exposure.
      Elucidating the mechanistic basis of uranium interactions is essential for
      monitoring the health risk. In the present study, we investigated the cellular
      mechanisms involved in uranyl nitrate-induced nephrotoxicity. Male Swiss albino
      mice were administrated with a single intraperitoneal dose of 2 and 4 mg/kg of
      uranyl nitrate at different time points 1, 3, 5, 7, 14, and 28 days. Uranyl
      nitrate intoxication-induced apoptosis in the kidney tissue was observed by TUNEL
      assay. To assess the proliferation, immunohistochemistry was performed using Ki67
      proliferative marker followed by western blotting to confirm the involvement of
      key signaling molecules. The number of TUNEL positive nuclei peaked at third day
      after uranyl nitrate insult. The increased expression of proliferation marker
      Ki67 suggests the enhanced DNA repair process prominently at seventh day. Uranyl
      nitrate administration also resulted in activation of extracellular signal
      regulated kinases (ERK), Akt, and c-Jun N-terminal kinases (JNK) expression. All
      these changes were found to be time-dependent. The result of the current study
      suggests that uranyl nitrate induces acute renal injury by activation of
      apoptosis through JNK pathway, while the early activation of signaling molecules
      Akt and ERK promotes the tubular cell proliferation and cell survival.

PMID- 30302619
TI  - Low survival rate of young adult-born olfactory sensory neurons in the undamaged
      mouse olfactory epithelium.
AB  - Olfactory sensory neurons (OSNs) are generated throughout life from progenitor
      cells in the olfactory epithelium. OSN axons project in an odorant receptor
      specific manner to the olfactory bulb (OB), forming an ordered array of glomeruli
      where they provide sensory input to OB neurons. The tetracycline transactivator
      (tTA) system permits developmental stage-specific expression of reporter genes in
      OSNs and has been widely used for structural and functional studies of the
      development and plasticity of the mouse olfactory system. However, the cellular
      ages at which OSNs stop expressing reporters driven by the immature OSN-specific
      Ggamma8-tTA driver line and begin to express reporters driven by the mature OSN
      specific OMP-tTA driver line have not been directly determined. We pulse-labeled
      terminally dividing cells in the olfactory epithelium of 28-day-old (P28) mice
      with EdU and analyzed EdU labeling in OSNs expressing fluorescent reporter
      proteins under control of either the Ggamma8-tTA or OMP-tTA driver line 5-14 days
      later. Expression of OMP-tTA-driven reporters began in 6-day-old OSNs, while the
      vast majority of newborn OSNs did not express Ggamma8-tTA-driven fluorescent
      proteins beyond 8 days of cellular age. Surprisingly, we also found a low
      survival rate for P28-born OSNs, very few of which survived for more than 14
      days. We propose that OSN survival requires the formation of stable synaptic
      connections and hence may be dependent on organismal age.

PMID- 30302618
TI  - The Expression of Hypoxia-Induced Gene 1 (Higd1a) in the Central Nervous System
      of Male and Female Rats Differs According to Age.
AB  - HIGD1A (hypoxia-induced gene domain protein-1a), a mitochondrial inner membrane
      protein present in various cell types, has been mainly associated with anti
      apoptotic processes in response to stressors. Our previous findings have shown
      that Higd1a mRNA is widely expressed across the central nervous system (CNS),
      exhibiting an increasing expression in the spinal cord from postnatal day 1 (P1)
      to 15 (P15) and changes in the distribution pattern from P1 to P90. During the
      first weeks of postnatal life, the great plasticity of the CNS is accompanied by
      cell death/survival decisions. So we first describe HIGD1A expression throughout
      the brain during early postnatal life in female and male pups. Secondly, based on
      the fact that in some areas this process is influenced by the sex of individuals,
      we explore HIGD1A expression in the sexual dimorphic nucleus (SDN) of the medial
      preoptic area, a region that is several folds larger in male than in female rats,
      partly due to sex differences in the process of apoptosis during this period.
      Immunohistochemical analysis revealed that HIGD1A is widely but unevenly
      expressed throughout the brain. Quantitative Western blot analysis of the
      parietal cortex, diencephalon, and spinal cord from both sexes at P1, P5, P8, and
      P15 showed that the expression of this protein is predominantly high and changes
      with age but not sex. Similarly, in the sexual dimorphic nucleus, the expression
      of HIGD1A varied according to age, but we were not able to detect significant
      differences in its expression according to sex. Altogether, these results suggest
      that HIGD1A protein is expressed in several areas of the central nervous system
      following a pattern that quantitatively changes with age but does not seem to
      change according to sex.

PMID- 30302621
TI  - Tolerability of mycophenolate sodium in renal transplant recipients.
AB  - Background Kidney transplant recipients (KTR) receive fixed daily doses of
      mycophenolate sodium as part of the immunosuppressive regimen. Dose reductions
      occur primarily due to adverse events and may be associated with an increased
      risk of acute rejection and graft loss. Objectives To evaluate the tolerability
      of mycophenolate in kidney transplant recipients receiving tacrolimus and
      prednisone. Setting The study was performed at Hospital do Rim, Federal
      University of Sao Paulo in Brazil. Method This was a retrospective cohort study
      including 506 patients. Tolerability of mycophenolate sodium was classified into
      the following groups: Temporary reduction (TR), definitive reduction (DR),
      temporary interruption (TI), permanent discontinuation (PD) and without
      modification (WM). Main outcome measure The cause of mycophenolate dose change
      and its influence on rejection-free survival during the first 3 years after
      transplantation. Results The cumulative incidence of dose change was 51.2%
      (11%TR, 44%DR, 24%TI, and 21%PD). Gastrointestinal (45.3%), infection (31.9%) and
      hematological (14.9%) systems accounted for most of the dose changes. The adverse
      events with higher incidence were diarrhea, cytomegalovirus (CMV) infection and
      leukopenia. Changes in dose of mycophenole were associated with reduced acute
      rejection-free survival compared with patients WM group (71.4%TR, 58.9%DR,
      56.7%TI, 53.7%PD vs. 74.2%WM, p = 0.020). Only patients with PD showed inferior
      patient (59.3% vs. 94.4%, p = 0.001) and death-censored graft (83.3% vs. 92.5%, p
      = 0.074) survivals compared to patients WM. Conclusion In this cohort, changes in
      the dose of mycophenolate were associated with increased risk of acute rejection
      and permanent discontinuation was associated with inferior patient and graft
      survival.

PMID- 30302620
TI  - Association of matrix metalloproteinase 3 and endogenous inhibitors with
      inflammatory markers in mitral valve disease and calcification.
AB  - Calcific mitral valve stenosis (MVS) is a common disease characterized by
      extensive remodeling of the extracellular matrix via matrix metalloproteinases
      (MMPs). The mechanism of calcification due to extensive matrix remodeling remains
      unclear. In this study, we investigated the relationship between MMP-3, tissue
      inhibitors of metalloproteinases (TIMPs) as well as pro-inflammatory cytokines
      and the phenomenon of calcification in MVS. 212 patients having rheumatic mitral
      stenosis (RMS) and 155 healthy control subjects were recruited in the Cardiology
      Department of La Rabta Hospital University. Levels of MMP-3, TIMPs, IL-6 and TNF
      alpha were measured by ELISA sandwich assay, hs-CRP was measured by
      immunoturbidimetry. Plasma levels of MMP-3, TIMP-1 and MMP-3/TIMP-2 ratio were
      lower only in RMS women in comparison to the control group. Calcification degree
      correlated positively with MMP-3 in women and men. In addition, calcification was
      correlated positively with MMP-3/TIMPs ratio in women patients. The inflammatory
      parameters were positively associated with extracellular matrix turnover
      biomarkers in men patients. In patients, the level of MMP-3 was increased in men
      and women with a calcification score >= 5. In addition, MMP-3 level predicted the
      occurrence of calcification. At ROC curves analysis, the cut-off MMP-3 level was
      in women was 9.21 ng/ml (sensitivity 51.1%, specificity 89.3%) and in men was
      12.84 ng/ml (sensitivity 78.6%, specificity 77.8%). The high levels of MMP-3 and
      the biomarkers of inflammation contribute to valvular remodeling and
      calcification of the mitral valve.

PMID- 30302622
TI  - Correlates of Emergency Department Service Utilization Among U.S. Chinese Older
      Adults.
AB  - Older adults visit emergency departments (EDs) at a disproportionally higher rate
      than other age groups. Prior studies examining racial disparities in ED
      utilization focus on African Americans and Hispanics. There is a dearth of
      information on ED utilization patterns among older Asian Americans despite the
      evidence that ED expenditures in Asian Americans are comparable to that of
      Caucasians. To address this knowledge gap, we examined factors associated with ED
      service utilization in the largest Asian subgroup, U.S. Chinese older adults.
      Cross-sectional data from the Population Study of Chinese Elderly in Chicago
      (PINE) (N = 3,157) were used. Multivariate negative binomial regression analyses
      were conducted to examine significant factors associated with ED use. Higher
      education (rate ratio [RR] = 1.03, 95% confidence interval [CI] 1.00-1.05) and
      acculturation levels (RR = 1.02, CI 1.00-1.04), fewer people in the household (RR
      = 0.94, CI 0.88-0.99), health insurance coverage (RR = 1.34, CI 1.01-1.78), lower
      income (RR = 0.89, CI 0.80-0.99), poorer perceived health (RR = 0.67, CI 0.58
      0.77), more functional limitations (RR = 1.09, CI 1.06-1.13) and depressive
      symptoms (RR = 1.04, CI 1.02-1.07), and a history of heart disease (RR = 2.28, CI
      1.83-2.84), stroke (RR = 1.68, CI 1.20-2.35), cancer (RR = 1.86, CI 1.31-2.63),
      and hip fracture (RR = 1.42, CI 1.02-1.98) were associated with higher rates of
      ED visits. Our findings highlight several significant correlates of ED use in
      U.S. Chinese older adults. Culturally-appropriate interventions modifying these
      factors have the potential to decrease ED visits and improve care outcomes in
      this population.

PMID- 30302623
TI  - Effect of Varying Viscosity on Two-Fluid Model of Blood Flow through Constricted
      Blood Vessels: A Comparative Study.
AB  - PURPOSE: Most of the previously studied non-Newtonian blood flow models
      considered blood viscosity to be constant but for correct measurement of flow
      rate and flow resistance, the hematocrit dependent viscosity will be better as
      various literature suggested the variable nature of blood viscosity. Present work
      concerns the steady and pulsatile nature of blood flow through constricted blood
      vessels. Two-fluid model for blood is considered with the suspension of all the
      RBCs (erythrocytes) in the core region as a non-Newtonian (Herschel-Bulkley)
      fluid and the plasma in the cell free region near wall as a Newtonian fluid. No
      slip condition on the wall and radially varying viscosity has been taken.
      METHODS: For steady flow the analytical approach has been taken to obtain the
      exact solution. Regular perturbation expansion method has been used to solve the
      governing equations for pulsatile flow up to first order of approximation by
      assuming the pulsatile Reynolds number to be very small (much less than unity).
      RESULTS: Flow rate, wall shear stress and velocity profile have been graphically
      analyzed and compared with constant viscosity model. A noteworthy observation of
      the present study is that rise in viscosity index leads to decay in velocity,
      velocity of plug flow region, flow rate while flow resistance increases with
      rising viscosity index (m). The results for Power-law fluid (PL), Bingham-plastic
      fluid (BP), Newtonian fluid (NF) are found as special cases from this model. Like
      the constant viscosity model, it has been also observed that the velocity, flow
      rate and plug core velocity of two-fluid model are higher than the single-fluid
      model for variable viscosity. CONCLUSIONS: The two-phase fluid model is more
      significant than the single-fluid model. Effect of viscosity parameter on various
      hemodynamical quantities has been obtained. It is also concluded that a rising
      viscosity parameter (varying nature of viscosity) significantly distinguishes the
      single and two-fluid models in terms of changes in blood flow resistance. The
      outcome of present study may leave a significant impact on analyzing blood flow
      through small blood vessels with constriction, where correct measurement of flow
      rate and flow resistance for medical treatment is very important.

PMID- 30302624
TI  - Real World Evidence: Time for a Switch?

PMID- 30302625
TI  - Acaricidal properties of ylang-ylang oil and star anise oil against nymphs of
      Ixodes ricinus (Acari: Ixodidae).
AB  - Ylang-ylang oil (YYO) from Cananga odorata (Lam.) Hook.f. & Thomson and star
      anise oil (SAO) from Illicium verum Hook.f. were tested at four concentrations
      0.05, 0.1, 0.2, 0.4 ul/cm2. Mortality rates were obtained by counting dead nymphs
      at 30-min intervals during the first 5 h after the start of exposure and then at
      24, 48 and 72 h. Mortality increased with increasing oil concentration and time
      of exposure. The two highest concentrations of YYO (0.2, 0.4 ul/cm2) gave maximum
      lethal concentrations (LC) of 50 and 95% mortality after 4.5 h exposure.
      Mortality of 95% was obtained after 24 h with the next highest dose (0.1 ul/cm2),
      whereas LC95 required 3 days with the lowest YYO (0.05 ul/cm2). The lethal effect
      time (LT) was correlated with the duration of exposure, with a significant effect
      at 0.4 MUl YYO/cm2 after 3 h' (LT50 = 3.2 h, LT95 = 4.3 h). In contrast, only the
      highest concentration of SAO, 0.4 ul SAO/cm2, showed increasing mortality with
      time of exposure. This reached LT50 after 10 h and LT95 after 24 h. However, with
      the lower concentration (0.2 ul/cm2) 50% mortality was reached after 24 h and
      100% at 72 h. At to the lowest concentration of SAO (0.1 ul/cm2), 67% mortality
      after 48 h. The study indicates that YYO and SAO exhibit strong acaricidal
      properties against nymphs of I. ricinus and suggest that both YYO and SAO should
      be evaluated as potentially useful in the control of ticks.

PMID- 30302626
TI  - Ixodes heathi n. sp. (Acari: Ixodidae), a co-endangered tick from the critically
      endangered mountain pygmy possum (Burramys parvus), with notes on its biology and
      conservation.
AB  - A new species of co-endangered tick, Ixodes heathi n. sp., is described from
      specimens of the nymph collected on the critically endangered mountain pygmy
      possum (Burramys parvus Broom) from the alpine region of Victoria, Australia. Its
      biology is discussed along with strategies for its conservation.

PMID- 30302627
TI  - Differential expression analysis for subolesin in Rhipicephalus microplus
      infected with Anaplasma marginale.
AB  - Rhipicephalus microplus (formerly Boophilus microplus) ticks are potential
      vectors of several pathogens of livestock especially in tropical and subtropical
      regions where may have substantial effects on economic development. Among tick
      borne pathogens, Anaplasma marginale is considered one of the most important in
      domestic and wild ruminants worldwide. Different molecular mechanisms have been
      employed by both ticks and these intracellular pathogens, in order to be able to
      adapt and survive. Subolesin, originally called 4D8, is an evolutionarily well
      preserved protein among ixodid tick species. This new antigen was found to be
      protective against tick infestations when used as a vaccine, as it has an
      essential role in tick blood digestion, development and infection of host cells
      by A. marginale. Recent studies have demonstrated that infection of both tick and
      vertebrate host cells with this microorganism changed gene expression. Therefore,
      the main objective of this study was to investigate subolesin expression in
      uninfected and A. marginale-infected R. microplus salivary glands by real-time
      reverse transcriptase (RT)-PCR. To analyze the differential expression of the
      recombinant protein subolesin, the gene was previously expressed from ticks
      infected with A. marginale. Results from this study revealed that, the expression
      of subolesin was significantly higher in salivary glands of infected R. microplus
      in comparison to uninfected ones.

PMID- 30302629
TI  - Pantoprazole Induces Mitochondrial Apoptosis and Attenuates NF-kappaB Signaling
      in Glioma Cells.
AB  - Gastric H+/K+-ATPase or vacuolar-ATPases (V-ATPases) are critical for the cancer
      cells survival and growth in the ischemic microenvironment by extruding protons
      from the cell. The drugs which inhibit V-ATPases are known as proton pump
      inhibitors (PPIs). In the present study, we aimed to evaluate the anticancer
      efficacy of pantoprazole (PPZ) and its consequences on NF-kappaB signaling in
      glioma cells. We have used MTT and clonogenic assay to show PPZ effect on glioma
      cell growth. Propidium iodide and rhodamine 123 staining were performed to
      demonstrate cell cycle arrest and mitochondrial depolarization. TUNEL staining
      was used to evidence apoptosis after PPZ treatment. Immunoblotting and
      immunofluorescence microscopy were performed to depict protein levels and
      localization, respectively. Luciferase assay was performed to confirm NF-kappaB
      suppression by PPZ. Our results revealed PPZ treatment inhibits cell viability or
      growth and induced cell death in a dose- and time-dependent manner. PPZ exposure
      arrested G0/G1 cyclic phase and increased TUNEL positivity, caspase-3 and PARP
      cleavage with altered pro and anti-apoptotic proteins. PPZ also induced ROS
      levels and depolarized mitochondria (Deltapsim) with increased cytosolic
      cytochrome c level. Further, PPZ suppressed TNF-alpha stimulated NF-kappaB
      signaling by repressing p65 nuclear translocation. NF-kappaB luciferase reporter
      assays revealed significant inhibition of NF-kappaB gene upon PPZ treatment. PPZ
      exposure also reduced the expression of NF-kappaB-associated genes, such as
      cyclin-D1, iNOS, and COX-2, which indicate NF-kappaB inhibition. Altogether, the
      present study disclosed that PPZ exerts mitochondrial apoptosis and attenuates NF
      kappaB signaling suggesting PPZ can be an effective and safe anticancer drug for
      glioma.

PMID- 30302630
TI  - Steroids in Stroke with Special Reference to Progesterone.
AB  - Both sex and steroid hormones are important to consider in human ischemic stroke
      and its experimental models. Stroke initiates a cascade of changes that lead to
      neural cell death, but also activates endogenous protective processes that
      counter the deleterious consequences of ischemia. Steroids may be part of these
      cerebroprotective processes. One option to provide cerebroprotection is to
      reinforce these intrinsic protective mechanisms. In the current review, we first
      summarize studies describing sex differences and the influence of steroid
      hormones in stroke. We then present and discuss our recent results concerning
      differential changes in endogenous steroid levels in the brains of male and
      female mice and the importance of progesterone receptors (PR) during the early
      phase after stroke. In the third part, we give an overview of experimental
      studies, including ours, that provide evidence for the pleiotropic beneficial
      effects of progesterone and its promising cerebroprotective potential in stroke.
      We also highlight the key role of PR signaling as well as potential additional
      mechanisms by which progesterone may provide cerebroprotection.

PMID- 30302628
TI  - Oxidative Imbalance, Nitrative Stress, and Inflammation in C6 Glial Cells Exposed
      to Hexacosanoic Acid: Protective Effect of N-acetyl-L-cysteine, Trolox, and
      Rosuvastatin.
AB  - X-linked adrenoleukodystrophy (X-ALD) is an inherited neurometabolic disorder
      caused by disfunction of the ABCD1 gene, which encodes a peroxisomal protein
      responsible for the transport of the very long-chain fatty acids from the cytosol
      into the peroxisome, to undergo beta-oxidation. The mainly accumulated saturated
      fatty acids are hexacosanoic acid (C26:0) and tetracosanoic acid (C24:0) in
      tissues and body fluids. This peroxisomal disorder occurs in at least 1 out of
      20,000 births. Considering that pathophysiology of this disease is not well
      characterized yet, and glial cells are widely used in studies of protective
      mechanisms against neuronal oxidative stress, we investigated oxidative damages
      and inflammatory effects of vesicles containing lecithin and C26:0, as well as
      the protection conferred by N-acetyl-L-cysteine (NAC), trolox (TRO), and
      rosuvastatin (RSV) was assessed. It was verified that glial cells exposed to
      C26:0 presented oxidative DNA damage (measured by comet assay and endonuclease
      III repair enzyme), enzymatic oxidative imbalance (high catalase activity),
      nitrative stress [increased nitric oxide (NO) levels], inflammation [high
      Interleukin-1beta (IL-1beta) levels], and induced lipid peroxidation (increased
      isoprostane levels) compared to native glial cells without C26:0 exposure.
      Furthermore, NAC, TRO, and RSV were capable to mitigate some damages caused by
      the C26:0 in glial cells. The present work yields experimental evidence that
      inflammation, oxidative, and nitrative stress may be induced by hexacosanoic
      acid, the main accumulated metabolite in X-ALD, and that antioxidants might be
      considered as an adjuvant therapy for this severe neurometabolic disease.

PMID- 30302631
TI  - In Vitro Skin Retention and Drug Permeation through Intact and Microneedle
      Pretreated Skin after Application of Propranolol Loaded Microemulsions.
AB  - PURPOSE: Topical beta-blockers are efficacious for treating infantile
      hemangiomas, but no formulations have been specifically optimized for skin
      delivery. Our objective was to quantify skin concentrations and drug permeation
      of propranolol (a nonselective beta-blocker) after application of microemulsions
      to intact and microneedle pretreated skin. METHODS: Four propranolol-loaded
      microemulsions were characterized for droplet size, surface charge, conductivity,
      pH, drug solubility, and drug release. Skin concentrations and drug permeation
      through skin were quantified using LC-MS. Skin-to-receiver ratios were used to
      compare the microemulsion formulations to a drug-in-PBS solution. RESULTS:
      Propranolol solubility was significantly greater in microemulsions vs PBS.
      Cumulative drug release from the microemulsions over 24 h ranged from 13 to 26%.
      Skin concentrations and drug permeation through intact skin was significantly
      higher from PBS; however, the skin-to-receiver ratios were significantly higher
      for water-rich microemulsions compared to PBS or surfactant-rich microemulsions.
      Microneedle pretreatment significantly increased skin concentrations for all
      formulations. Skin-to-receiver ratios significantly increased after microneedle
      pretreatment for surfactant-rich microemulsions. CONCLUSIONS: Microemulsion
      formulation can be altered to elicit different drug delivery profiles through MN
      treated skin. This could be advantageous for maximizing local skin drug
      concentrations and improving dosing schedules for infantile hemangioma treatment.

PMID- 30302633
TI  - Accuracy of an artificial neural network for detecting a regional abnormality in
      myocardial perfusion SPECT.
AB  - OBJECTIVES: The patient-based diagnosis with an artificial neural network (ANN)
      has shown potential utility for the detection of coronary artery disease;
      however, the region-based accuracy of the detected regions has not been fully
      evaluated. The aim of this study was to demonstrate the accuracy of all detected
      regions compared with expert interpretation. METHODS: A total of 109 abnormal
      regions including 33 regions with stress defects and 76 regions with ischemia
      were examined, which were derived from 21 patients who underwent myocardial
      perfusion SPECT within 45 days of coronary angiography. The gray and color scale
      images, a polar map of stress, rest and difference, and left ventricular function
      were displayed on the monitor to score the extent and severity of stress defect
      and ischemia. Two experienced nuclear medicine physicians (Observers A and B)
      scored the abnormality with a 4-point scale and draw abnormal regions on a polar
      map. The gold standard was determined by the final judgment of normal or abnormal
      by the consensus of two other independent expert nuclear cardiologists, and was
      compared with the stress defect and ischemia derived from ANN. RESULTS: The
      concordance rate of ANN to the gold standard was higher than that of two
      observers. Furthermore, the kappa coefficient indicated moderate to substantial
      agreement for stress defect and slight to the fair agreement for ischemia. The
      area under the curve (AUC) of ANN was the highest for both stress defect and
      ischemia; in particular, the ANN of ischemia showed significantly higher AUC than
      Observer A (p = 0.005). The ANN of stress defect showed higher specificity
      compared with two observers, while the ANN of ischemia showed higher sensitivity.
      Consequently, the accuracy of ANN showed the highest in this study. CONCLUSION:
      The ANN-based regional diagnosis showed a high concordance rate with the gold
      standard and comparable or even higher than the interpretation by nuclear
      medicine physicians.

PMID- 30302632
TI  - Expression, Purification, and Characterization of Recombinant Human alpha1
      Antitrypsin Produced Using Silkworm-Baculovirus Expression System.
AB  - Human alpha1-antitrypsin (AAT) is the most abundant serine proteinase inhibitor
      (serpin) in the human plasma. Commercially available AAT for the medications of
      deficiency of alpha1-antitrypsin is mainly purified from human plasma. There is a
      high demand for a stable and low-cost supply of recombinant AAT (rAAT). In this
      study, the baculovirus expression vector system using silkworm larvae as host was
      employed and a large amount of highly active AAT was recovered from the silkworm
      serum (~ 15 mg/10 ml) with high purity. Both the enzymatic activity and stability
      of purified rAAT were comparable with those of commercial product. Our results
      provide an alternative method for mass production of the active rAAT in
      pharmaceutical use.

PMID- 30302634
TI  - Differential diagnosis of thickened myocardium: an illustrative MRI review.
AB  - OBJECTIVES: The purpose of this article is to describe the key cardiac magnetic
      resonance imaging (MRI) features to differentiate hypertrophic cardiomyopathy
      (HCM) phenotypes from other causes of myocardial thickening that may mimic them.
      CONCLUSIONS: Many causes of myocardial thickening may mimic different HCM
      phenotypes. The unique ability of cardiac MRI to facilitate tissue
      characterisation may help to establish the aetiology of myocardial thickening,
      which is essential to differentiate it from HCM phenotypes and for appropriate
      management. TEACHING POINTS: * Many causes of myocardial thickening may mimic
      different HCM phenotypes. * Differential diagnosis between myocardial thickening
      aetiology and HCM phenotypes may be challenging. * Cardiac MRI is essential to
      differentiate the aetiology of myocardial thickening from HCM phenotypes.

PMID- 30302635
TI  - Imaging presentation of pancreatic neuroendocrine neoplasms.
AB  - Pancreatic neuroendocrine neoplasms (P-NENs) are the second most common solid
      pancreatic neoplasms. P-NENs have a wide range of imaging features presentations
      and they can be detected with typical and atypical imaging presentations. Typical
      and atypical appearances can be explained by pathologic correlations. P-NENs are
      generally hypervascular lesions, showing a typical enhancement behavior after
      contrast media injection during imaging methods, but they could also have
      different imaging features, creating some difficulty in differential diagnosis.
      For this reason, radiologists should be aware of different imaging presentations
      of these neoplasms. Radiological evaluation has a critical role in P-NENs
      identification, characterization, and staging of these neoplasms, especially in
      those cases in which surgery is the treatment of choice. The present paper shows,
      indicating the underlying pathologic correlations, typical and atypical
      presentations of NENs. KEY POINTS: * P-NENs have a wide range of imaging features
      presentations, typical and atypical. * Pathology could help in better
      understanding the typical P-NENs appearance at imaging. * P-NENs are generally
      hypervascular lesions. * Radiological evaluation has a critical role in P-NENs
      identification and management. * Radiologists should know every type of different
      imaging presentation of P-NENs to better diagnose these kinds of lesions.

PMID- 30302636
TI  - Sensitivity Analysis for Multiscale Stochastic Reaction Networks Using Hybrid
      Approximations.
AB  - We consider the problem of estimating parameter sensitivities for stochastic
      models of multiscale reaction networks. These sensitivity values are important
      for model analysis, and the methods that currently exist for sensitivity
      estimation mostly rely on simulations of the stochastic dynamics. This is
      problematic because these simulations become computationally infeasible for
      multiscale networks due to reactions firing at several different timescales.
      However it is often possible to exploit the multiscale property to derive a
      "model reduction" and approximate the dynamics as a Piecewise deterministic
      Markov process, which is a hybrid process consisting of both discrete and
      continuous components. The aim of this paper is to show that such PDMP
      approximations can be used to accurately and efficiently estimate the parameter
      sensitivity for the original multiscale stochastic model. We prove the
      convergence of the original sensitivity to the corresponding PDMP sensitivity, in
      the limit where the PDMP approximation becomes exact. Moreover, we establish a
      representation of the PDMP parameter sensitivity that separates the contributions
      of discrete and continuous components in the dynamics and allows one to
      efficiently estimate both contributions.

PMID- 30302637
TI  - Postoperative Complications Independently Predict Cancer-Related Survival in
      Peritoneal Malignancies.
AB  - BACKGROUND: The authors hypothesized that postoperative complications after
      cytoreductive surgery-hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC)
      have a negative impact on perioperative and oncologic outcomes and that the novel
      Comprehensive Comorbidity Index (CCI) would be a better predictor of such
      outcomes than the traditional Clavien-Dindo classification (CDC). METHODS: The
      study used a prospective database of 1296 patients with peritoneal metastases
      (PM) undergoing CRS-HIPEC between 2001 and 2016. The Kaplan-Meier method was used
      to estimate survival. Multivariate analyses identified associations with
      perioperative and oncologic outcomes. The Akaike information criterion and the
      Schwarz (Bayesian information) criterion were used to compare model fitting for
      CCI versus CDC. RESULTS: In this study, CRS-HIPEC was performed for malignant
      mesothelioma (12%) and PM from appendix (50%), colorectal (30%), and ovarian (8%)
      cancers. Major postoperative in-hospital complications (CDC grades 3-4) occurred
      for 24% of the patients. However, a range of CCI scores was calculated for each
      CDC grade because 36% of the patients experienced multiple complications. After a
      median follow-up period of 55 months, the median progression-free survival was 15
      months, and the median overall survival was 39 months. In the multivariate Cox
      proportional hazards models, postoperative in-hospital complications (measured by
      CDC or CCI) were independent prognostic factors for 30-day post-discharge
      morbidity and readmission, as well as for survival. The CCI scores demonstrated
      higher prognostic sensitivity for these outcomes than CDC grades. CONCLUSIONS:
      Reduction of postoperative complications after CRS-HIPEC is essential for optimal
      short- and long-term outcomes. For assessing total burden of postoperative
      complications per patient, CCI is superior to CDC and more sensitive for
      assessing surgery- and cancer-related outcomes after CRS-HIPEC.

PMID- 30302638
TI  - ASO Author Reflections: Toward Improved Selection of Patients for Cytoreduction
      and HIPEC: Identification of Prognostic Factors for Patients with Colorectal
      Peritoneal Metastases.

PMID- 30302639
TI  - ASO Author Reflections: Contact Between T and N Classifications in Pancreatic
      Neuroendocrine Neoplasms.

PMID- 30302640
TI  - ASO Author Reflections: Addressing Surgery-Specific Risk Factors Influencing Time
      to Chemotherapy in Breast Cancer.

PMID- 30302641
TI  - ASO Author Reflections: Anatomic Variations Around the Middle Colic Artery and
      the Middle Colic Vein.

PMID- 30302642
TI  - ASO Author Reflections: Clinical Value of PET-CT for Gastric Cancer.

PMID- 30302643
TI  - Both Ultrasound Features and Nuclear Atypia are Associated with Malignancy in
      Thyroid Nodules with Atypia of Undetermined Significance.
AB  - BACKGROUND: The optimal management of thyroid nodules that undergo fine-needle
      aspiration (FNA) with findings of atypia of undetermined significance (AUS) is
      unclear. Categorizing nodules by AUS subtype and ultrasound characteristics may
      improve risk stratification. Therefore, the purpose of this study is to evaluate
      the association between AUS subtype and ultrasound features on risk of malignancy
      (ROM). METHODS: We performed a review of all patients with a thyroid nodule who
      underwent an FNA at our institution between January 2010 and November 2015.
      Patients with AUS were divided into groups with (1) nuclear atypia, (2)
      architectural atypia, or (3) Hurthle cell atypia. Their ultrasound features were
      assessed using the American Thyroid Association (ATA) thyroid nodule sonographic
      patterns. We conducted a univariate and multivariable analysis to determine the
      association between AUS subtype and other variables of interest with ROM.
      RESULTS: Of the 3428 thyroid nodules that underwent FNA, 237 (6.9%) had AUS. Of
      the 97 surgically resected nodules, 67 (69%) were benign and 30 (31%) were
      malignant. On univariate analysis nuclear atypia (p < 0.01) was associated with a
      thyroid malignancy. On multivariable analysis, both ATA high-risk ultrasound
      features (p = 0.04, odds ratio [OR] 3.68) and nuclear atypia (p < 0.01, OR 11.8)
      were independently associated with a final diagnosis of thyroid carcinoma.
      CONCLUSIONS: Nuclear atypia and ATA high-risk ultrasound features are useful in
      identifying patients with AUS that are at a higher risk of thyroid malignancy.
      Surgeons should take these factors into consideration when evaluating patients
      with AUS.

PMID- 30302644
TI  - ASO Author Reflections: Multimodal Enhanced Recovery After Surgery (ERAS) Program
      in Totally Laparoscopic Distal Gastrectomy for Gastric Cancer: What Have We
      Learned?

PMID- 30302645
TI  - ASO Author Reflections: Improving Patient Selection for Sentinel Lymph Node
      Biopsy After Neoadjuvant Chemotherapy.

PMID- 30302646
TI  - ASO Author Reflections: Factors that Predict Performance of Sentinel Lymph Node
      Biopsy and the Association with Improved Survival for Melanoma Patients Who Have
      Nodal Staging.

PMID- 30302647
TI  - Pigments in an iridescent bacterium, Cellulophaga fucicola, isolated from
      Antarctica.
AB  - An iridescent yellow pigmented bacterium isolated from the Antarctic continent,
      named Cellulophaga fucicola strain 416, was found to be able to tolerate UV-B
      radiation. Its crude pigment extract was tested for antioxidant capacity, UV
      light stability and phototoxicity profile against murine fibroblast lines. The
      pigments were further isolated and chemically identified by ultra-high
      performance liquid chromatography with photodiode array and mass spectrometry
      detectors. The results showed that the pigment extract presented weak stability
      under exposure to UV light, a phototoxic profile in the 3t3 Neutral Red Uptake
      test and a very high antioxidant activity, suggesting that it could be used as
      food and feed colourants. Zeaxanthin and two isomers of zeaxanthin, beta
      cryptoxanthin and beta-carotene, were identified using a C18 column. These five
      carotenoids were the major pigments isolated from C. fucicola 416. In conclusion,
      the identification of pigments produced by the bacterial strain under study may
      help us understand how bacteria thrive in high UV and cold environments, and
      opens avenues for further biotechnological application towards a more sustainable
      and environmentally friendly way of pigment exploitation.

PMID- 30302648
TI  - Streptomyces monticola sp. nov., a novel actinomycete isolated from soil.
AB  - A novel actinobacterium, designated strain NEAU-GS4T, was isolated from soil
      collected from Mount Song and characterised using a polyphasic approach. 16S rRNA
      gene sequence similarity studies showed that strain NEAU-GS4T belongs to the
      genus Streptomyces, being closely related to Streptomyces spectabilis JCM 4308T
      (98.8%), Streptomyces sclerotialus DSM 43032T (98.3%) and Streptomyces
      lasiicapitis 3H-HV17(2)T (98.0%). A multilocus sequence analysis based on five
      house-keeping genes (atpD, gyrB, rpoB, recA and trpB) also indicated that strain
      NEAU-GS4T should be assigned to the genus Streptomyces. The major menaquinones
      were identified as MK-9(H6), MK-9(H8) and MK-9(H4). The polar lipid profile was
      found to contain diphosphatidylglycerol, phosphatidylmethylethanolamine,
      phosphatidylethanolamine, phosphatidylinositolmannosides and an unidentified
      phospholipid. The major fatty acids were identified as anteiso-C15:0, iso-C16:0
      and anteiso-C17:0. Moreover, DNA-DNA hybridization results and some phenotypic
      characteristics indicated that strain NEAU-GS4T can be clearly differentiated
      from its closely related species of the genus Streptomyces. Therefore, it is
      concluded that strain NEAU-GS4T represents a novel species of the genus of
      Streptomyces, for which the name Streptomyces monticola sp. nov. is proposed. The
      type stain is NEAU-GS4T (=CGMCC 4.7467T = DSM 105116T).

PMID- 30302649
TI  - Characterization of a strain representing a new Enterobacter species,
      Enterobacter chengduensis sp. nov.
AB  - An Enterobacter strain, WCHECl-C4, was recovered from a human blood sample in
      China in 2015. Phylogenetic analysis based on multi-locus sequence analysis of
      the rpoB, gyrB, infB and atpD housekeeping genes revealed that the strain is
      distinct from any previously described species of the genus Enterobacter. The
      whole genome sequence of strain WCHECl-C4 has an 80.48-93.34% average nucleotide
      identity with those of type strains of all known Enterobacter species. In silico
      DNA-DNA hybridization (isDDH) values between strain WCHECl-C4 and type strains of
      all known Enterobacter species range from 23.2 to 52.4%. The major cellular fatty
      acids of strain WCHECl-C4 are C16:0, C17:0 cyclo and C18:1omega7c, which are in
      the range of Enterobacter species. The genomic DNA G + C content was 55.7 mol%.
      Strain WCHECl-C4 can be distinguished from all known Enterobacter species by its
      ability to ferment D-sorbitol, L-rhamnose and melibiose but with a negative Voges
      Proskauer reaction. Genotypic and phenotypic characteristics from this study
      indicate that strain WCHECl-C4 represents a novel species of the genus
      Enterobacter, for which the name Enterobacter chengduensis sp. nov. is proposed.
      The type strain is WCHECl-C4T (= GDMCC1.1216T = CCTCC AB 2017105T = KCTC 52993T).

PMID- 30302651
TI  - Risk of multiple colorectal cancer development depends on age and subgroup in
      individuals with hereditary predisposition.
AB  - Development of multiple colorectal cancers (CRCs), synchronously or
      metachronously, is associated with hereditary predisposition for cancer and
      accurate risk estimates of multiple tumour development are relevant to recommend
      rational surveillance programs. A cross-sectional study design was used to
      estimate the risks of synchronous CRC (SCRC) and metachronous CRC (MCRC) based on
      data from the National Danish Hereditary Nonpolyposis Register. In total, 7100
      individuals from families within the subgroups Lynch syndrome, familial CRC (FCC)
      and moderate risk were used with estimates relative to a non-hereditary
      population control cohort. SCRC was diagnosed in 7.4% of the Lynch syndrome
      cases, in 4.2% of FCC cases and 2.5% of the moderate risk cases, which translated
      to relative risks of 1.9-5.6. The risk of MCRC was distinctively linked to Lynch
      syndrome with a life-time risk up to 70% and an incidence rate ratio of 5.0. The
      risk of SCRC was significantly increased in all subgroups of FCC and hereditary
      CRC, whereas the risk of MCRC was specifically linked to Lynch syndrome. These
      observations suggest that individuals with FCC or hereditary CRC should be
      carefully screened for second primary CRC at the time of diagnosis, whereas
      intensified surveillance for second primary CRC is motivated in Lynch syndrome
      with lower-intensity programs in families with yet unidentified genetic causes.

PMID- 30302650
TI  - Marinobacter profundi sp. nov., a slightly halophilic bacterium isolated from a
      deep-sea sediment sample of the New Britain Trench.
AB  - A piezotolerant, cold-adapted, slightly halophilic bacterium, designated strain
      PWS21T, was isolated from a deep-sea sediment sample collected from the New
      Britain Trench. Cells were observed to be Gram-stain negative, rod-shaped,
      oxidase- and catalase-positive. Growth of the strain was observed at 4-45 
      degrees C (optimum 37  degrees C), at pH 5.0-9.0 (optimum 7.0) and in 0.5-20%
      (w/v) NaCl (optimum 3-4%). The optimum pressure for growth was 0.1 MPa
      (megapascal) with tolerance up to 70 MPa. 16S rRNA gene sequence analysis showed
      that strain PWS21T is closely related to Marinobacter guineae M3BT (98.4%) and
      Marinobacter lipolyticus SM19T (98.2%). Multilocus sequence analysis (MLSA) based
      on sequences of housekeeping genes gyrB, recA, atpD, rpoB and rpoD indicates that
      strain PWS21T represents a distinct evolutionary lineage within the genus
      Marinobacter. Furthermore, strain PWS21T showed low ANI and diDDH values to the
      closely related species. The principal fatty acids were identified as C12:0,
      C12:0 3-OH, C16:1omega9c, C16:0 and C18:1omega9c. Ubiquinone-9 was identified as
      the major respiratory quinone. The polar lipids were identified as
      phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol
      (DPG), aminophospholipid (APL), two unidentified lipids and an unidentified
      phospholipid (PL). The G + C content of the genomic DNA was determined to be 60.3
      mol%. On the basis of phenotypic, chemotaxonomic and molecular data, we conclude
      that strain PWS21T represents a novel species of the genus Marinobacter, for
      which the name Marinobacter profundi sp. nov. is proposed (type strain PWS21T =
      KCTC 52990T = MCCC 1K03345T).

PMID- 30302652
TI  - Boosting care and knowledge about hereditary cancer: European Reference Network
      on Genetic Tumour Risk Syndromes.
AB  - Approximately 27-36 million patients in Europe have one of the ~ 5.000-8.000
      known rare diseases. These patients often do not receive the care they need or
      they have a substantial delay from diagnosis to treatment. In March 2017, twenty
      four European Reference Networks (ERNs) were launched with the aim to improve the
      care for these patients through cross border healthcare, in a way that the
      medical knowledge and expertise travels across the borders, rather than the
      patients. It is expected that through the ERNs, European patients with a rare
      disease get access to expert care more often and more quickly, and that research
      and guideline development will be accelerated resulting in improved diagnostics
      and therapies. The ERN on Genetic Tumour Risk Syndromes (ERN GENTURIS) aims to
      improve the identification, genetic diagnostics, prevention of cancer, and
      treatment of European patients with a genetic predisposition for cancer. The ERN
      GENTURIS focuses on syndromes such as hereditary breast cancer, hereditary
      colorectal cancer and polyposis, neurofibromatosis and more rare syndromes e.g.
      PTEN Hamartoma Tumour Syndrome, Li Fraumeni Syndrome and hereditary diffuse
      gastric cancer.

PMID- 30302653
TI  - Endoscopic Ultrasound-Directed Transgastric ERCP (EDGE): a Single-Center US
      Experience with Follow-up Data on Fistula Closure.
AB  - BACKGROUND: Endoscopic ultrasound-directed transgastric ERCP (EDGE) by creating
      an anastomosis from the gastric pouch or jejunum to the excluded stomach allows
      performance of ERCP in Roux-en-Y gastric bypass (RYGB) anatomy. Concern for
      persistent fistula following stent removal and sparse data limit adoption.
      METHODS: Retrospective review of consecutive patients undergoing EDGE over a 2
      year period. RESULTS: Nineteen RYGB patients underwent EDGE; three had previously
      failed ERCP by the device-assisted method. Indications for ERCP were
      choledocholithiasis (8), recurrent acute pancreatitis (6), benign post-surgical
      stricture (3), elevated bilirubin, and papillary stenosis (1 each). EDGE was
      technically successful in all 19 patients with jejunogastric anastomosis in 11
      patients and gastrogastric in 8 using a 15-mm lumen-apposing metal stent. Stent
      malposition occurred in six and was managed by rescue maneuvers. ERCP was
      performed in the same session in four patients; the remainder were delayed after
      a mean of 48 days. Diagnostic endoscopic ultrasound (EUS) was performed in four
      patients. No severe adverse events occurred; clinical success was 100%. Stents
      were removed after a mean dwell time of 182 days. Argon plasma coagulation (APC)
      was used to promote fistula closure in 12 patients. Upper GI series to assess
      fistula closure was obtained in 11 patients after a mean of 182 days following
      stent removal. One persistent fistula was identified and closed endoscopically.
      CONCLUSIONS: EDGE is an effective modality for performing ERCP in patients with
      RYGB anatomy and can be performed via gastrogastric or jejunogastric approaches.
      Persistent fistula is uncommon and can be managed endoscopically. APC may promote
      fistula closure.

PMID- 30302654
TI  - Effect of hospital and surgeon volume on postoperative outcomes after distal
      gastrectomy for gastric cancer based on data from 145,523 Japanese patients
      collected from a nationwide web-based data entry system.
AB  - BACKGROUND: Despite interest in surgeon and hospital volume effects on distal
      gastrectomy, clinical significance has not been confirmed in a large-scale
      population. We studied to clarify the effects of surgeon and hospital volume on
      postoperative mortality after distal gastrectomy for gastric cancer among
      Japanese patients in a nationwide web-based data entry system. METHODS: We
      extracted data on distal gastrectomy for gastric cancer from the National
      Clinical Database between 2011 and 2015. The primary outcome was operative
      mortality. Hospital volume was divided into 3 tertiles: low (1-22 cases per
      year), medium (23-51) and high (52-404). Surgeon volume was divided into the 5
      groups: 0-3, 4-10, 11-20, 21-50, 51 + cases per year. We calculated the 95%
      confidence interval (CI) for the mortality rate based on odds ratios (ORs)
      estimated from a hierarchical logistic regression model. RESULTS: We analyzed
      145,523 patients at 2182 institutions. Operative mortality was 1.9% in low-, 1.0%
      in medium- and 0.5% in high-volume hospitals. The operative mortality rate
      decreased definitively with surgeon volume, 1.6% in the 0-3 group and 0.3% in the
      51 + group. After risk adjustment for surgeon and hospital volume and patient
      characteristics, hospital volume was significantly associated with operative
      morality (medium: OR 0.64, 95% CI 0.56-0.73, P < 0.001; high: OR 0.42, 95% CI
      0.35-0.51, P < 0.001). CONCLUSIONS: We demonstrate that hospital volume can have
      a crucial impact on postoperative mortality after distal gastrectomy compared
      with surgeon volume in a nationwide population study. These findings suggest that
      centralization may improve outcomes after distal gastrectomy.

PMID- 30302655
TI  - The Role of Gay-Related Stigma in HIV-Risk Behavior Among Sexual Minority Men in
      Europe.
AB  - Sexual orientation stigma stems from discriminatory social contexts and may
      ultimately impact the behavioral health of stigmatized individuals through stress
      related pathways. Sexual minority stigma is of particular concern in Europe given
      the diversity of social contexts on the continent and sexual minority men's
      rapidly increasing risk of HIV infection, especially in Central and Eastern
      Europe, potentially rooted in stigma. This study assesses whether stigma in the
      ubiquitous social contexts surrounding sexual minority men (e.g., family,
      workplace, government) may place them at higher risk for HIV contraction across
      six countries. We utilized a large cross-sectional survey sample of HIV-negative
      sexual minority men (N = 2087; mean age = 31.6, SD = 9.7) from six European
      countries to test whether those who reported sexual orientation stigma also
      engaged in more HIV risk-related behaviors, including condomless sex with casual
      partners (in the absence of PrEP) and substance use before and during sex.
      Regression analyses were performed in Mplus. We found that a one standard
      deviation increase in reported sexual orientation stigma was significantly
      associated with the following during the last sexual encounter: a 19% increase in
      odds of sex under the influence of alcohol, 27% increase in odds of sex under the
      influence of cannabis, 49% increase in odds of sex under the influence of illicit
      drugs, an 11% increase in odds of condomless sex with casual partners in the past
      6 months, and a 26% increase in odds of knowing where to receive an HIV test.
      Sexual minority men who reported perceiving greater sexual orientation-related
      stigma within their ubiquitous social contexts were significantly more likely to
      report sexual risk and alcohol and drug use during their last sexual encounter,
      yet reported more knowledge of preventive services. Contextual stigma might serve
      as a precursor to behavioral risks of HIV infection, generating maladaptive
      stress responses capable of being modified through individually-focused
      interventions. Structural interventions are also needed to ultimately reduce
      stigma at its source.

PMID- 30302656
TI  - The fourth trimester: toward improved postpartum health and healthcare of mothers
      and their families in the United States.

PMID- 30302657
TI  - Choosing a sensible cut-off point: assessing the impact of uncertainty in a
      social network on the performance of NBDA.
AB  - Network-based diffusion analysis (NBDA) has become a widely used tool to detect
      and quantify social learning in animal populations. NBDA infers social learning
      if the spread of a novel behavior follows the social network and hence relies on
      appropriate information on individuals' network connections. Most studies on
      animal populations, however, lack a complete record of all associations, which
      creates uncertainty in the social network. To reduce this uncertainty,
      researchers often use a certain threshold of sightings for the inclusion of
      animals (which is often arbitrarily chosen), as observational error decreases
      with increasing numbers of observations. Dropping individuals with only few
      sightings, however, can lead to information loss in the network if connecting
      individuals are removed. Hence, there is a trade-off between including as many
      individuals as possible and having reliable data. We here provide a tool in R
      that assesses the sensitivity of NBDA to error in the social network given a
      certain threshold for the inclusion of individuals. It simulates a social
      learning process through a population and then tests the power of NBDA to
      reliably detect social learning after introducing observational error into the
      social network, which is repeated for different thresholds. Our tool can help
      researchers using NBDA to select a threshold, specific to their data set, that
      maximizes power to reliably quantify social learning in their study population.

PMID- 30302658
TI  - Left ventricular assist device recovery: does duration of mechanical support
      matter?
AB  - Heart failure is a widespread condition in the United States that is predicted to
      significantly increase in prevalence in the next decade. Many heart failure
      patients are given a left ventricular assist device (LVAD) while they wait for a
      heart transplant, while those that are not able to undergo a heart transplant may
      be given an LVAD permanently. However, past studies have observed a small subset
      of heart failure patients that recovered cardiac function of their native heart
      after being placed on an LVAD. As a result, some patients have been able to have
      their LVAD explanted and no longer needed a heart transplant. In this review, we
      analyzed the data of 15 studies that observed recovery of cardiac function in
      LVAD patients in order to investigate the effects that duration of LVAD support
      has on patient outcomes. From our review, we identified that there may be
      negative consequences of prolonged duration of mechanical support such as
      myocardial atrophy and abnormal calcium cycling as well as circumstances that may
      allow for a longer duration of LVAD support such as in patients using a
      continuous-flow LVAD, non-ischemic cardiomyopathy patients, and the specific
      pharmacological therapy.

PMID- 30302659
TI  - The use of mandibular advancement devices in obstructive sleep apnea: a proven
      and effective therapy.

PMID- 30302660
TI  - Bioactive Phospholipids Enhance Migration and Adhesion of Human Leukemic Cells by
      Inhibiting Heme Oxygenase 1 (HO-1) and Inducible Nitric Oxygenase Synthase (iNOS)
      in a p38 MAPK-Dependent Manner.
AB  - Bioactive phospholipids, including sphingosine-1-phosphate (S1P), ceramide-1
      phosphate (C1P), lysophosphatidylcholine (LPC), and its derivative
      lysophosphatidic acid (LPA), have emerged as important mediators regulating the
      trafficking of normal and cancer cells. While the role of S1P in regulating
      migration of hematopoietic cells is well established, in this work we compared
      its biological effects to the effects of C1P, LPC, and LPA. We employed 10 human
      myeloid and lymphoid cell lines as well as blasts from AML patients. We observed
      that human leukemic cells express functional receptors for phospholipids and
      respond to stimulation by phosphorylation of p42/44 MAPK and AKT. We also found
      that bioactive phospholipids enhanced cell migration and adhesion of leukemic
      cells by downregulating expression of HO-1 and iNOS in a p38 MAPK-dependent
      manner but did not affect cell proliferation. By contrast, downregulation of p38
      MAPK by SB203580 enhanced expression of HO-1 and iNOS and decreased migration of
      leukemic cells in vitro and their seeding efficiency to vital organs in vivo
      after injection into immunodeficient mice. Based on these findings, we
      demonstrate that, besides S1P, human leukemic cells also respond to C1P, LPC, and
      LPA. Since the prometastatic effects of bioactive phospholipids in vivo were
      mediated, at least in part, by downregulating HO-1 and iNOS expression in a p38
      MAPK-dependent manner, we propose that inhibitors of p38 MAPK or stimulators of
      HO-1 activity will find application in inhibiting the spread of leukemic cells in
      response to bioactive phospholipids.

PMID- 30302661
TI  - Self-propulsion of droplets driven by an active permeating gel.
AB  - We discuss the flow field and propulsion velocity of active droplets, which are
      driven by body forces residing on a rigid gel. The latter is modelled as a porous
      medium which gives rise to permeation forces. In the simplest model, the Brinkman
      equation, the porous medium is characterised by a single lengthscale [Formula:
      see text] --the square root of the permeability. We compute the flow fields
      inside and outside of the droplet as well as the energy dissipation as a function
      of [Formula: see text]. We furthermore show that there are optimal gel fractions,
      giving rise to maximal linear and rotational velocities. In the limit [Formula:
      see text], corresponding to a very dilute gel, we recover Stokes flow. The
      opposite limit, [Formula: see text], corresponding to a space filling gel, is
      singular and not equivalent to Darcy's equation, which cannot account for self
      propulsion.

PMID- 30302662
TI  - Transmucosal oxygen tension of the clitoris: a new parameter for future
      investigations of the sexual, metabolic, and cardiovascular health of women.
AB  - BACKGROUND: Several studies suggested that abnormalities in tissue perfusion of
      external genitalia and vagina can lead to female sexual dysfunctions (FSDs) and
      can be associated to metabolic and cardiovascular risk factors. However, there
      are some technical difficulties in assessing these abnormalities. The measurement
      of oxygen partial pressure is a noninvasive method to measure oxygen partial
      pressure (pO2) at the skin surface to assess tissue perfusion. The aim of this
      study was to evaluate whether transmucosal oxygen tension (TmPO2) can be measured
      at the mucosal surface of clitoris and whether the measurements are reliable.
      METHODS: TmPO2 was measured in six young healthy women by using a device to
      measure transcutaneous pO2 on the skin and by choosing a small sensor, usually
      used for newborns. The identical procedure for the detection of pO2 at the skin
      surface was used. RESULTS: The mean value of TmPO2 was 42.3 mmHg (range: 24.1
      53.4 mmHg). All the trend curves of the TmPO2 showed the same behavior: after a
      stabilization time, there was a stable pO2 (plateau phase) that corresponds to
      the TmPO2 of the clitoris. These curves had a similar trend to those recorded at
      the skin surface. CONCLUSIONS: TmPO2 can be easily measured at the mucosal
      surface of clitoris. Large epidemiological studies in healthy and unhealthy women
      and in women with FSD are needed to establish both the normal range of TmPO2 and
      the meaning that different values of TmPO2 can have on sexual and general health
      of the women.

PMID- 30302663
TI  - Long-term sequelae of the less than total thyroidectomy procedures for benign
      thyroid nodular disease.
AB  - INTRODUCTION: Nodular goiter is the most common disorder of the thyroid gland.
      Less than total thyroidectomy procedures are considered the gold standard in the
      surgical management of nodular thyroid disease despite its propensity for
      recurrence. The aim of the study was to assess long-term sequelae of the less
      than total thyroidectomy procedures. MATERIAL AND METHODS: In this single-center
      retrospective study, records of 154 patients that underwent less than total
      thyroidectomy, for nodular disease and/or hyperthyroidism between 1998 and 2013,
      were reviewed. Patients with malignant findings in the histology report and a
      follow-up of less than 5 years were excluded. RESULTS: The mean age of the
      recorded patients was 65.1 +/- 12.91 years of which 132 were females. Subtotal
      thyroidectomy was performed in 45.5% of the study population, 22.1% underwent
      partial thyroidectomy, while the remaining 32.5% underwent lobectomy. Long-term
      thyroxine supplementation was administered in 138 patients (89.6%). Recurrence of
      clinically important nodules (>1 cm) was observed in 68.2% of patients but only
      11% of the population underwent completion thyroidectomy. In the univariate
      analysis, the duration of follow-up (p = 0.00005, C.I.: 0.903-0.965) as well as
      the type of operation (p = 0.035, C.I.: 1.031-2.348) appeared to have a
      significant correlation with nodular recurrence. The multivariate analysis
      identified the duration of follow-up (p = 0.0005, C.I.: 0.908-0.973) as the only
      significant predictive factor of nodular recurrence. CONCLUSION: This is the
      first study with such a long duration of post-operative follow-up. The high rate
      of nodular recurrence in less than total thyroidectomy procedures along with the
      lifelong need for thyroxine supplementation suggest that a more conservative
      surgical approach is needed. When surgery is recommended, we suggest total
      thyroidectomy as the treatment of choice to avoid the recurrence of disease, the
      high cost associated with frequent follow-ups by means of sonography as well as
      thyroxine replacement therapy.

PMID- 30302664
TI  - Health-Related Quality of Life Following Concussion in Collegiate Student
      Athletes With and Without Concussion History.
AB  - The purpose of this study was to compare global and specific health-related
      quality of life (HRQOL) throughout concussion recovery between those with and
      without concussion history. Student-athletes diagnosed with concussion completed
      global (Short Form-12v2; SF-12) and specific (Hospital Anxiety and Depression
      Scale: HADS) HRQOL assessments at baseline, 24-48 h, asymptomatic, return-to
      play, and 6-months post-injury. Baseline scores were compared to post-injury time
      points for SF-12 subscores (physical and mental; PCS-12, MCS-12) and HADS
      subscores (depression and anxiety; HADS-D, HADS-A). We conducted a 2 * 5 mixed
      model ANOVA for group (with and without concussion history) and time (four post
      injury assessments compared to baseline). We did not observe interaction or main
      effects for group, except those with concussion history had worse HADS-D
      subscores than those without concussion history. PCS-12 subscores were worse at
      24-48 h, asymptomatic, and return-to-play compared to baseline, but returned to
      baseline 6-months post-injury. MCS-12 subscores did not differ at any time
      points. HADS-D subscores worsened 24-48 h post-injury, but improved for
      additional assessments compared to baseline. HADS-A improved post-injury compared
      to baseline at asymptomatic, return-to-play, and 6-month assessments, but was
      similar to baseline 24-48 h post-injury. HRQOL physical aspects slightly worsened
      post-injury and restored to baseline after returning to play.

PMID- 30302665
TI  - Excitatory and inhibitory effects of stimulation of sacral dorsal root ganglion
      on bladder reflex in cats.
AB  - PURPOSE: To explore the effects of electrical stimulation of the sacral dorsal
      root ganglion (DRG) on bladder reflexes in alpha-chloralose-anesthetized cats.
      METHODS: Bladder activity was recorded under isovolumetric conditions. A pair of
      hook electrodes was placed in the right S1 and S2 DRGs of 12 adult male cats,
      which were stimulated over a range of frequencies (0.25-30 Hz) and at threshold
      intensity. RESULTS: Stimulation of S1 and S2 DRGs inhibited or evoked bladder
      contractions under isovolumetric conditions depending on the frequency of
      stimulation in nine cats. Stimulation at low frequencies (3-7 Hz on S1 or S2 DRG)
      significantly inhibited isovolumetric rhythmic bladder contractions, while
      excitatory effects were observed at two frequency ranges, including lower
      frequencies (0.25-1.5 Hz on S1 DRG and 0.25-1.25 Hz on S2 DRG) and middle
      frequencies (15-30 Hz on S1 and S2 DRGs). CONCLUSIONS: These results suggest that
      the sacral DRG might be a potential valuable target for electrical stimulation in
      the treatment of bladder dysfunction.

PMID- 30302666
TI  - The comparison of oxidative stress effect in classic and tubeless percutaneous
      nephrolithotomy.
AB  - PURPOSE: Surgical stone treatment induces oxidative stress in kidney tissue. We
      hypothesized that tubeless percutaneous nephrolithotomy (tPCNL) may induce less
      oxidative stress than classic percutaneous nephrolithotomy (cPCNL) with
      nephrostomy tube. METHODS: Seventy-two consecutive patients with kidney stones
      qualified for PCNL were enrolled in the study. Patients were assigned to one of
      two groups (first group 33 patients-cPCNL and second group 39 patients-tPCNL).
      Four urine samples were collected in four consecutive days, starting the day
      before operation. Four oxidative stress markers were analyzed in each sample:
      catalase (CAT), protein sulfhydryl group (SH), total antioxidant capacity (TAC)
      and superoxide dismutase (SOD). RESULTS: Baseline mean levels of CAT (IU/l), SH
      (MUmol/l), TAC (mmol/l) and SOD (NU/ml) were 19.4 versus 11.7; 18 versus 58.7;
      2.02 versus 1.99; 20.5 versus 22.6 in cPCNL and tPCNL group, respectively. On day
      two, the levels were 89 versus 104.9; 334.7 versus 518.9; 1.87 versus 1.79; 33.7
      versus 41.4, respectively. On the third day, the levels were: 67.4 versus 28.3;
      206.8 versus 306.9; 2.01 versus 2.06; 38.2 versus 36.6, respectively. On the
      fourth day, the concentrations were 47.4 versus 18.5; 129.3 versus 208.7; 2
      versus 2.06; 35 versus 45.2, respectively. Significant differences were observed
      only for CAT and TAC concentrations in days 3 (p = 0.04 and 0.04) and 4 (p = 0.02
      and < 0.001) in favor of tPCNL. CONCLUSIONS: CAT, SH and SOD significantly rise
      after operation. TAC represents the inversion of other parameters. CAT is
      significantly lower, and TAC is significantly higher in tPCNL postoperatively
      favoring this method.

PMID- 30302667
TI  - Application of fractal theory and fuzzy enhancement in ultrasound image
      segmentation.
AB  - The manuscript describes an ultrasound image segmentation technique based on the
      fractional Brownian motion (FBM) model. Here, the ultrasound images are first
      enhanced using a fuzzy-based technique, and later the FBM model is employed to
      obtain the fractal features used for segmentation. The novelty lies in combining
      the fuzzy-enhancement technique and FBM model, and further illustrating that
      fractal length-based segmentation provides better results than fractal dimension
      based segmentation. Experimental results on ultrasound images of carotid artery
      clearly illustrate that the segmentation outputs obtained from fractal length are
      superior, and the high qualitative values of DSC, Precision, Recall and F1 score
      (0.9617, 0.9629, 0.9653 and 0.9641 respectively), together with a low value of
      APD (1.9316), indicate that the proposed method is comparable to other state-of
      the-art segmentation techniques. Graphical abstract Summary of proposed technique
      - overall design flow.

PMID- 30302668
TI  - Pregnancy-Associated Plasma Protein A (PAPP-A) Concentration in Population of
      Healthy Young People: Interactions with Tobacco Smoke and Anti-oxidative Status.
AB  - Pregnancy-associated plasma protein A (PAPP-A) is a high-molecular zinc-binding
      metalloproteinase that was first detected in the serum of pregnant women. It can
      also be detected in men and non-pregnant women. Recently, a growing interest in
      determining the concentration of PAPP-A as a marker of oxidative stress and
      atherosclerotic processes has been observed. Among the factors that could
      potentially influence the PAPP-A formation is the exposure to tobacco smoke. Some
      components of tobacco smoke have an immediate effect on the body and also direct
      influence on the cardiovascular system. The aim of this study was to evaluate the
      relation between PAPP-A concentration and either passive or active exposure to
      tobacco smoke in the population of medicine students (n = 152). The relation
      between PAPP-A concentration and chosen markers of inflammatory response and anti
      oxidative processes was analyzed. The samples of serum, urine, and saliva were
      collected and main nicotine metabolites in urine samples were determined using
      ELISA technique. Comparison of the PAPP-A concentrations in the study group
      revealed that in the group of active smokers, the concentration of the protein
      was significantly higher than in the group of passive smokers (p = .04) and the
      group of not-exposed students (p = .006). PAPP-A concentration showed significant
      positive correlation with the values of FRAP and main nicotine metabolites. The
      evident influence of both active and passive tobacco smoke exposure on PAPP-A
      levels in the studied population of young people who in general are not included
      in the group of high-risk cardiovascular incidents, shows how important early
      prevention of anti-health behaviors is.

PMID- 30302669
TI  - Phenolic Metabolites Modulate Cardiomyocyte Beating in Response to Isoproterenol.
AB  - Cardiovascular disease (CVD) is a public health concern, and the third cause of
      death worldwide. Several epidemiological studies and experimental approaches have
      demonstrated that consumption of polyphenol-enriched fruits and vegetables can
      promote cardioprotection. Thus, diet plays a key role in CVD development and/or
      prevention. Physiological beta-adrenergic stimulation promotes beneficial
      inotropic effects by increasing heart rate, contractility and relaxation speed of
      cardiomyocytes. Nevertheless, chronic activation of beta-adrenergic receptors can
      cause arrhythmias, oxidative stress and cell death. Herein the cardioprotective
      effect of human metabolites derived from polyphenols present in berries was
      assessed in cardiomyocytes, in response to chronic beta-adrenergic stimulation,
      to disclose some of the underlying molecular mechanisms. Ventricular
      cardiomyocytes derived from neonate rats were treated with three human
      bioavailable phenolic metabolites found in circulating human plasma, following
      berries' ingestion (catechol-O-sulphate, pyrogallol-O-sulphate, and 1
      methylpyrogallol-O-sulphate). The experimental conditions mimic the physiological
      concentrations and circulating time of these metabolites in the human plasma (2
      h). Cardiomyocytes were then challenged with the beta-adrenergic agonist
      isoproterenol (ISO) for 24 h. The presence of phenolic metabolites limited ISO
      induced mitochondrial oxidative stress. Likewise, phenolic metabolites increased
      cell beating rate and synchronized cardiomyocyte beating population, following
      prolonged beta-adrenergic receptor activation. Finally, phenolic metabolites also
      prevented ISO-increased activation of PKA-cAMP pathway, modulating Ca2+
      signalling and rescuing cells from an arrhythmogenic Ca2+ transients' phenotype.
      Unexpected cardioprotective properties of the recently identified human
      circulating berry-derived polyphenol metabolites were identified. These
      metabolites modulate cardiomyocyte beating and Ca2+ transients following beta
      adrenergic prolonged stimulation.

PMID- 30302670
TI  - From opening the 'black box' to looking behind the curtain: cognition and context
      in assessor-based judgements.
AB  - The increasing use of direct observation tools to assess routine performance has
      resulted in the growing reliance on assessor-based judgements in the workplace.
      However, we have a limited understanding of how assessors make judgements and
      formulate ratings in real world contexts. The current research on assessor
      cognition has largely focused on the cognitive domain but the contextual factors
      are equally important, and both are closely interconnected. This study aimed to
      explore the perceived cognitive and contextual factors influencing Mini-CEX
      assessor judgements in the Emergency Department setting. We used a conceptual
      framework of assessor-based judgement to develop a sequential mixed methods
      study. We analysed and integrated survey and focus group results to illustrate
      self-reported cognitive and contextual factors influencing assessor judgements.
      We used situated cognition theory as a sensitizing lens to explore the
      interactions between people and their environment. The major factors highlighted
      through our mixed methods study were: clarity of the assessment, reliance on and
      variable approach to overall impression (gestalt), role tension especially when
      giving constructive feedback, prior knowledge of the trainee and case complexity.
      We identified prevailing tensions between participants (assessors and trainees),
      interactions (assessment and feedback) and setting. The two practical
      implications of our research are the need to broaden assessor training to
      incorporate both cognitive and contextual domains, and the need to develop a more
      holistic understanding of assessor-based judgements in real world contexts to
      better inform future research and development in workplace-based assessments.

PMID- 30302672
TI  - Administrative Medical Databases for Clinical Research: The Good, The Bad, and
      The Ugly.

PMID- 30302671
TI  - The swimming of a deforming helix.
AB  - Many microorganisms and artificial microswimmers use helical appendages in order
      to generate locomotion. Though often rotated so as to produce thrust, some
      species of bacteria such Spiroplasma, Rhodobacter sphaeroides and Spirochetes
      induce movement by deforming a helical-shaped body. Recently, artificial devices
      have been created which also generate motion by deforming their helical body in a
      non-reciprocal way (A. Mourran et al. Adv. Mater. 29, 1604825, 2017). Inspired by
      these systems, we investigate the transport of a deforming helix within a viscous
      fluid. Specifically, we consider a swimmer that maintains a helical centreline
      and a single handedness while changing its helix radius, pitch and wavelength
      uniformly across the body. We first discuss how a deforming helix can create a
      non-reciprocal translational and rotational swimming stroke and identify its
      principle direction of motion. We then determine the leading-order physics for
      helices with small helix radius before considering the general behaviour for
      different configuration parameters and how these swimmers can be optimised.
      Finally, we explore how the presence of walls, gravity, and defects in the
      centreline allow the helical device to break symmetries, increase its speed, and
      generate transport in directions not available to helices in bulk fluids.

PMID- 30302673
TI  - Analysis of Multifloral Bee Pollen Pellets by Advanced Digital Imaging Applied to
      Functional Food Ingredients.
AB  - Bee pollen is a hive product, resulting from floral pollen agglutination by
      worker bees and it is characterized by its excellent bioactive and nutritional
      composition. Currently, research is focused on bee pollen applications on food
      industry, because this product has been considered an excellent source of
      compounds for human nutrition. It is also important in some industries, where
      color and particle size are important characteristics for production. Due to the
      granular nature of bee pollen, conventional colorimetry does not allow describing
      color correctly; thus, digital image analysis is a better alternative. This
      technique could also allow classifying bee pollen according to its appearance
      beyond the color. Consequently, the aim of this work was to develop a novel
      methodology for image data processing to classify bee pollen as ingredient in
      food industry. Seven color groups in samples were established regarding harvest
      month and particle size. It was possible to calculate the percentage of each
      color group in all samples. This methodology also allowed selecting each fraction
      for different applications in food industry using colorimetry, granulometry and
      the relationship between both of them.

PMID- 30302674
TI  - Hematopoietic Cell Transplant (HCT) in the Elderly: Myths, Controversies and
      Unknowns.
AB  - The incidence of most hematological malignancies increases with age. Despite the
      higher incidence of hematological malignancies in the elderly, the geriatric
      population is poorly represented in the early oncology clinical trials that
      established the current standards of care. Hematopoietic cell transplant (HCT),
      either upfront or at relapse, provides a potentially life-prolonging, often
      curative option for many patients with hematological malignancies and is
      considered the standard of care, at least for younger patients. Historically, the
      concern that older adults undergoing HCT may experience higher morbidity and
      transplant-related complications has limited the use of this potentially curative
      option to younger adults, particularly in allogeneic (allo-) HCT. There is
      growing evidence to support the feasibility, tolerability, and relatively similar
      effectiveness of both autologous and allo-HCT in the geriatric population. In the
      allo-HCT setting, nonmyeloablative/reduced-intensity conditioning (NMA/RIC) has
      expanded the spectrum of patients that can be considered for this approach.
      Overall survival is largely affected by disease stage, performance status, and
      comorbidities rather than by chronological age per se. Comprehensive geriatric
      assessment (CGA) is a promising tool that can uncover frequently undocumented
      vulnerabilities in an elderly transplant-eligible patient. Serial study of CGA
      throughout the peri-HCT period may help predict the short- and long-term impact
      of HCT on an older adult's functional status and quality of life. Further
      research is needed to evaluate whether early intervention to improve such
      vulnerabilities can improve survival and quality of life of these older patients.

PMID- 30302675
TI  - ?

PMID- 30302676
TI  - ?

PMID- 30302677
TI  - ?

PMID- 30302678
TI  - ?

PMID- 30302679
TI  - [We are not stuck in traffic, we are the traffic jam].

PMID- 30302680
TI  - [Clinical examination of the hip joint].

PMID- 30302681
TI  - [Patient with icterus: How do you find the diagnosis?]

PMID- 30302682
TI  - [Patient with dysnea in medical practice].

PMID- 30302683
TI  - [Managing hypothyroidism in general practice].

PMID- 30302685
TI  - ?

PMID- 30302684
TI  - [Hyperthyreodism for family physicians].

PMID- 30302686
TI  - ?

PMID- 30302687
TI  - ?

PMID- 30302688
TI  - ?

PMID- 30302689
TI  - ?

PMID- 30302690
TI  - ?

PMID- 30302691
TI  - ?

PMID- 30302692
TI  - ?

PMID- 30302693
TI  - ?

PMID- 30302694
TI  - ?

PMID- 30302695
TI  - ?

PMID- 30302696
TI  - ?

PMID- 30302697
TI  - ?

PMID- 30302699
TI  - ?

PMID- 30302698
TI  - ?

PMID- 30302700
TI  - ?

PMID- 30302701
TI  - ?

PMID- 30302703
TI  - ?

PMID- 30302702
TI  - ?

PMID- 30302704
TI  - ?

PMID- 30302705
TI  - ?

PMID- 30302706
TI  - ?

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TI  - ?

PMID- 30302709
TI  - ?

PMID- 30302710
TI  - ?

PMID- 30302711
TI  - ?

PMID- 30302713
TI  - ?

PMID- 30302714
TI  - ?

PMID- 30302715
TI  - ?

PMID- 30302716
TI  - ?

PMID- 30302717
TI  - [Treatment of anxiety disorders].

PMID- 30302718
TI  - Gender (De)Transitioning Before Puberty? A Response to Steensma and Cohen
      Kettenis (2011).

PMID- 30302719
TI  - Adipocyte proteome and secretome influence inflammatory and hormone pathways in
      glioma.
AB  - Gliomas represent the most common primary malignant brain tumors in adults, with
      an extremely poor prognosis. Among several risk factors, lifestyle was also
      recently identified as a major risk factor for the development of primary glioma.
      In the present study, we explore the relationship between obesity and glioma in a
      cellular model. Thus, we have study the influence of adipocytes secretome on
      glioma cell line GL261. Using the 3T3-L1 adipocyte cell line, and its conditioned
      medium (adipokines-enriched medium), we showed that adipocyte-released factors
      relate with glioma angiogenic, growth, hormones and metabolic behavior by MALDI
      TOF-MS and proteomic array analysis. In a first view, STI1, hnRNPs and PGK1 are
      under expressed on CGl. Similarly, both carbonic anhydrase and aldose reductase
      are even suppressed in glioma cells that grown under adipokines-enriched
      environment. Contrariwise, RFC1, KIF5C, ANXA2, N-RAP and RACK1 are overexpressed
      in GL261 cell the in the presence of the adipokines-enriched medium. We further
      identified the factors that are released by adipocyte cells, and revealed that
      several pro-inflammatory and angiogenic factors, such as IL-6, IL-11, LIF, PAI-1,
      TNF-alpha, endocan, HGF, VEGF IGF-I, were secreted to the medium into a high
      extent, whereas TIMP-1 and SerpinE1 were under expressed on CGl. This study
      discloses an interesting in vitro model for the study of glioma biology under a
      "obesity" environment, that can be explored for the understanding of cancer cells
      biology, for the search of biomarkers, prognostic markers and therapeutic
      approaches.

PMID- 30302721
TI  - Improved Glycemic Control with Insulin Glargine 300 U/mL (Toujeo(r)) in Patients
      with Type 2 Diabetes: Real-World Effectiveness in Switzerland.
AB  - INTRODUCTION: Insulin glargine 300 U/mL (Gla-300, Toujeo(r)) is a long-acting,
      once-daily basal insulin with improved-more stable and smoother-pharmacokinetic
      and pharmacodynamic profiles compared to insulin glargine 100 U/mL (Gla-100) and
      insulin degludec (IDeg). These properties have been shown to translate into an
      effective HbA1c reduction with the advantage of a lower risk of hypoglycemia in
      randomized controlled trials of Gla-300 versus Gla-100. In this study, we
      assessed the effectiveness and safety of Gla-300 under real-world conditions in
      Switzerland. METHODS: The prospective, observational, open-label, multicenter
      study TOP-2 explored the effectiveness of Gla-300 in adult patients with type 2
      diabetes (T2D) uncontrolled (HbA1c 7.5-10%) on their previous basal insulin in
      Germany, Austria, and Switzerland. The primary endpoints were the percentages of
      patients achieving a fasting plasma glucose (FPG) of <= 6.1 mmol/L after 6 and 12
      months. Secondary endpoints included changes in HbA1c, FPG, body weight, and
      insulin dose as well as hypoglycemia incidence and safety. Here we report the
      results for the Swiss patient cohort after 12 months of treatment with insulin
      glargine 300 U/mL. RESULTS: The 62 patients (33 men) had a mean age of 65 years,
      a mean diabetes duration of 14 years, a mean body mass index (BMI) of 31 kg/m2,
      and were mainly switched from Gla-100 (44%) to Gla-300. The most common
      concomitant oral anti-diabetes therapy was metformin (65%). The mean individual
      HbA1c target chosen by the investigators was 7.4%. After 12 months of therapy,
      Gla-300 significantly reduced mean HbA1c from 8.2% to 7.6% (p < 0.0001).
      Likewise, Gla-300 significantly reduced mean FPG from 9.1 mmol/L to 7.4 mmol/L (p
      < 0.0001). At study end, 32% of patients achieved FPG <= 6.1 mmol/L, 55% achieved
      FPG <= 7.2 mmol/L , and 57% achieved their individual HbA1c target. Gla-300 was
      uptitrated to a mean dose of 40 units per day. Symptomatic hypoglycemia incidence
      after 12 months was low at 9.7% and a rate of 0.23 events per patient year. Body
      weight remained stable and was not significantly altered during the study.
      CONCLUSION: Upon switching basaI insulin to Gla-300, overall glucose control
      significantly improved and glycemic targets were achieved with a low rate of
      hypoglycemia in T2D patients under real-world conditions in Switzerland. FUNDING:
      Sanofi-Aventis (Suisse) SA.

PMID- 30302722
TI  - Correlation Between Different Stages of Diabetic Nephropathy and Neuropathy in
      Patients with T2DM: A Cross-Sectional Controlled Study.
AB  - INTRODUCTION: Early detection of diabetic peripheral neuropathy (DPN) is critical
      in patients with type 2 diabetes mellitus (T2DM) due to the lack of targeted
      therapy for DPN. We have investigated the relationship between different stages
      of diabetic nephropathy and DPN in an attempt to elucidate whether albuminuria
      can be used as an early warning signal of DPN progression. METHODS: A total of
      217 T2DM patients who met the inclusion criteria were recruited from the
      Department of Endocrinology, Nanfang Hospital between January 2016 and June 2016.
      These patients were placed in groups based on urinary albumin excretion rate
      (UAER) and estimated glomerular filtration rate. Nerve conduction studies, the
      Semmes-Weinstein monofilament test (SWMT) and the vibration perception threshold
      (VPT) test were conducted. Multiple linear regression analysis, multivariate
      logistic regression and receiver-operating characteristic (ROC) analysis were
      performed to investigate the relationship between different stages of diabetic
      nephropathy and DPN in these patients. RESULTS: Significant differences were
      observed in the conduction velocity (CV) and amplitude of sensory/motor nerve
      potential among the T2DM patients at different stages of diabetic nephropathy
      (all p  < 0.05). The UAER and duration of diabetes were found to be independent
      factors associated with the mean CV and amplitude of sensory/motor nerve
      potential (all p  < 0.05). A disease duration of > 10 years (p  = 0.025) and a
      higher total cholesterol value (p  = 0.024) were found to be significantly
      associated with abnormal SWMT results. A UAER of > 300 mg/24 h (p  = 0.007) and a
      diastolic blood pressure of > 100 mmHg (p  = 0.042) were associated with a higher
      risk for abnormal VPT. A UAER  of > 300 mg/24 h (p  < 0.001) and a disease
      duration of > 10 years (p  = 0.02) were observed to be significantly correlated
      with DPN. The ROC analysis showed that the optimal cutoff values of UAER and
      duration as indicators of DPN were 90.5 mg/24 h and 9.5 years, respectively (both
      p  < 0.001). CONCLUSIONS: The results suggest that diabetic nephropathy is
      closely associated with the development of DPN in T2DM patients and that UAER and
      disease duration can be used as warning indicators of DPN progression. CHINESE
      CLINICAL TRIALS REGISTER NUMBER: ChiCTR-ROC-16007701.

PMID- 30302723
TI  - Tumor Type-Agnostic Treatment and the Future of Cancer Therapy.

PMID- 30302724
TI  - Methamphetamine (MA) Use Induces Specific Changes in LINE-1 Partial Methylation
      Patterns, Which Are Associated with MA-Induced Paranoia: a Multivariate and
      Neuronal Network Study.
AB  - The use of psychoactive substances, including methamphetamine (MA) may cause
      changes in DNA methylation. The aim of this study was to examine the effects of
      MA use on long interspersed element-1 (LINE-1) methylation patterns in
      association with MA-induced paranoia. This study recruited 123 normal controls
      and 974 MA users, 302 with and 672 without MA-induced paranoia. The Semi
      Structured Assessment for Drug Dependence and Alcoholism was used to assess
      demographic and substance use variables. Patterns of LINE-1 methylation were
      assessed in peripheral blood mononuclear cells and a combined bisulfite
      restriction analysis (COBRA) was used to estimate overall LINE-1 methylation (mC)
      while COBRA classified LINE-alleles into four patterns based on the methylation
      status of two CpG dinucleotides on each strand from 5' to 3', namely two
      methylated (mCmC) and two unmethylated (uCuC) CpGs and two types of partially
      methylated loci (mCuC that is 5'm with 3'u and uCmC that is 5'u with 3'm CpGs).
      MA users showed higher % mCuC and % mCuC + uCmC levels than controls. Use of
      solvents and opioids, but not cannabis and alcohol dependence, significantly
      lowered % uCmC levels, while current smoking significantly increased % uCuC
      levels. MA-induced paranoia was strongly associated with changes in LINE-1
      partial methylation patterns (lowered % uCmC), heavy MA use, lower age at onset
      of MA use, and alcohol dependence. Women who took contraceptives showed
      significantly lower LINE-1 % mC and % mCmC and higher % uCuC levels than women
      without contraceptive use and men. The results show that MA-induced changes in
      LINE-1 partial methylation patterns are associated with MA-induced paranoia and
      could explain in part the pathophysiology of this type of psychosis. It is argued
      that MA-induced neuro-oxidative pathways may have altered LINE-1 partial
      methylation patterns, which in turn may regulate neuro-oxidative and immune
      pathways, which may increase risk to develop MA-induced paranoia.

PMID- 30302720
TI  - Oxidative Stress and Inflammation, Key Targets of Atherosclerotic Plaque
      Progression and Vulnerability: Potential Impact of Physical Activity.
AB  - Atherosclerosis, a complex cardiovascular disease, is a leading cause of
      mortality and morbidity worldwide. Oxidative stress and inflammation are both
      involved in the development of atherosclerotic plaque as they increase the
      biological processes associated with this pathology, such as endothelial
      dysfunction and macrophage recruitment and adhesion. Atherosclerotic plaque
      rupture leading to major ischemic events is the result of vulnerable plaque
      progression, which is a result of the detrimental effect of oxidative stress and
      inflammation on risk factors for atherosclerotic plaque rupture, such as
      intraplaque hemorrhage, neovascularization, and fibrous cap thickness. Thus, both
      are key targets for primary and secondary interventions. It is well recognized
      that chronic physical activity attenuates oxidative stress in healthy subjects
      via the improvement of antioxidant enzyme capacities and inflammation via the
      enhancement of anti-inflammatory molecules. Moreover, it was recently shown that
      chronic physical activity could decrease oxidative stress and inflammation in
      atherosclerotic patients. The aim of this review is to summarize the role of
      oxidative stress and inflammation in atherosclerosis and the results of
      therapeutic interventions targeting them in both preclinical and clinical
      studies. The effects of chronic physical activity on these two key processes are
      then reviewed in vulnerable atherosclerotic plaques in both coronary and carotid
      arteries.

PMID- 30302725
TI  - Differential Methylation of H3K79 Reveals DOT1L Target Genes and Function in the
      Cerebellum In Vivo.
AB  - The disruptor of telomeric silencing 1-like (DOT1L) mediates methylation of
      histone H3 at position lysine 79 (H3K79). Conditional knockout of Dot1l in mouse
      cerebellar granule cells (Dot1l-cKOAtoh1) led to a smaller external granular
      layer with fewer precursors of granule neurons. Dot1l-cKOAtoh1 mice had impaired
      proliferation and differentiation of granular progenitors, which resulted in a
      smaller cerebellum. Mutant mice showed mild ataxia in motor behavior tests. In
      contrast, Purkinje cell-specific conditional knockout mice showed no obvious
      phenotype. Genome-wide transcription analysis of Dot1l-cKOAtoh1 cerebella using
      microarrays revealed changes in genes that function in cell cycle, cell
      migration, axon guidance, and metabolism. To identify direct DOT1L target genes,
      we used genome-wide profiling of H3K79me2 and transcriptional analysis. Analysis
      of differentially methylated regions (DR) and differentially expressed genes (DE)
      revealed in total 12 putative DOT1L target genes in Dot1l-cKOAtoh1 affecting
      signaling (Tnfaip8l3, B3galt5), transcription (Otx1), cell migration and axon
      guidance (Sema4a, Sema5a, Robo1), cholesterol and lipid metabolism (Lss, Cyp51),
      cell cycle (Cdkn1a), calcium-dependent cell-adhesion or exocytosis (Pcdh17,
      Cadps2), and unknown function (Fam174b). Dysregulated expression of these target
      genes might be implicated in the ataxia phenotype observed in Dot1l-cKOAtoh1.

PMID- 30302727
TI  - Increased STAT1 Amounts Correlate with the Phospho-STAT1 Level in STAT1 Gain-of
      function Defects.

PMID- 30302728
TI  - Faith-Based Groups as a Bridge to the Community for Military Veterans:
      Preliminary Findings and Lessons Learned in Online Surveying.
AB  - This report examines responses to a brief online survey, comparing how faith
      based (n = 27) and non-faith-based (n = 61) organizations engage with Veteran
      populations as well as the supportive services they provide. Data were analyzed
      using two-sample z-tests and Chi-squared tests. No significant differences were
      noted between respondents for self-reported confidence in responding to health
      care issues/concerns or engagement with Veteran populations. Faith-based
      respondents were found to provide significantly less mental health, suicide
      prevention, education/outreach, and other services, while providing significantly
      more spiritual care. There appears to be ample opportunity for expanding the
      supportive services provided by faith-based organizations.

PMID- 30302729
TI  - Our health counts: population-based measures of urban Inuit health determinants,
      health status, and health care access.
AB  - OBJECTIVE: Health determinants and outcomes are not well described for the
      growing population of Inuit living in southern urban areas of Canada despite
      known and striking health disparities for Inuit living in the north. The
      objective of this study was to work in partnership with Tungasuvvingat Inuit (TI)
      to develop population prevalence estimates for key indicators of health,
      including health determinants, health status outcomes, and health services access
      for Inuit in Ottawa, Canada. METHODS: We employed community-based respondent
      driven sampling (RDS) and a comprehensive health assessment survey to collect
      primary data regarding health determinants, status, and service access. We then
      linked with datasets held by the Institute for Clinical Evaluative Sciences
      (ICES), including hospitalization, emergency room, and health screening records.
      Adjusted population-based prevalence estimates and rates were calculated using
      custom RDS software. RESULTS: We recruited 341 Inuit adults living in Ottawa. The
      number of Inuit living, working or accessing health and social services in the
      City of Ottawa was estimated to be 3361 (95% CI 2309-4959). This population
      experiences high rates of poverty, unemployment, household crowding, and food
      insecurity. Prevalence of hypertension (25%; 95% CI 18.1-33.9), chronic
      obstructive pulmonary disease (6.7%; 95% CI 3.1-10.6), cancer (6.8%; 95% CI 2.7
      11.9), and rates of emergency room access were elevated for Inuit in Ottawa
      compared to the general population. Access to health services was rated fair or
      poor by 43%. Multiple barriers to health care access were identified.
      CONCLUSIONS: Urban Inuit experience a heavy burden of adverse health determinants
      and poor health status outcomes. According to urban Inuit in Ottawa, health
      services available to Inuit at the time of the study were inadequate.

PMID- 30302730
TI  - Assessing the ratio of Bacillus spores and vegetative cells by shotgun
      proteomics.
AB  - Mass spectrometry for rapid identification of microorganisms is expanding over
      the last years because this approach is quick. This methodology provides a
      decisive interest to fight against bioterrorism as it is applicable whatever the
      pathogen to be considered and often allows subtyping which may be crucial for
      confirming a massive and widespread attack with biological agents. Here, we
      present a methodology based on next-generation proteomics and tandem mass
      spectrometry for discovering numerous protein biomarkers allowing the
      discrimination of spores and vegetative cells of Bacillus atrophaeus, a
      biowarfare simulant. We propose a global quantitative evaluation of the two
      groups of discriminant biomarkers based on their aggregated normalized spectral
      abundance factors.

PMID- 30302726
TI  - Fourth Update on the Iranian National Registry of Primary Immunodeficiencies:
      Integration of Molecular Diagnosis.
AB  - BACKGROUND: The number of inherited diseases and the spectrum of clinical
      manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding.
      Molecular diagnosis using genomic approaches should be performed for all PID
      patients since it provides a resource to improve the management and to estimate
      the prognosis of patients with these rare immune disorders. METHOD: The current
      update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly
      registered patients during last 5 years (2013-2018) and the result of molecular
      diagnosis in patients enrolled for targeted and next-generation sequencing.
      RESULTS: Considering the newly diagnosed patients (n = 1395), the total number of
      registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical
      centers. The predominantly antibody deficiency was the most common subcategory of
      PID (29.5%). The putative causative genetic defect was identified in 1014
      patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these
      patients. Among the genetically different categories of PID patients, the
      diagnostic rate was highest in defects in immune dysregulation and lowest in
      predominantly antibody deficiencies and mutations in the MEFV gene were the most
      frequent genetic disorder in our cohort. CONCLUSIONS: During a 20-year
      registration of Iranian PID patients, significant changes have been observed by
      increasing the awareness of the medical community, national PID network
      establishment, improving therapeutic facilities, and recently by inclusion of the
      molecular diagnosis. The current collective study of PID phenotypes and genotypes
      provides a major source for ethnic surveillance, newborn screening, and genetic
      consultation for prenatal and preimplantation genetic diagnosis.

PMID- 30302731
TI  - Dissipation of polycyclic aromatic hydrocarbons (PAHs) in soil amended with
      sewage sludge and sludge compost.
AB  - In this study, greenhouse experiments were conducted under the condition of
      different amendment ratios and planting tall fescue (Festuca arundinacea). The
      amendment ratios of sewage sludge or sludge compost to soil were of 0, 10, 25,
      and 50% (w/w). The removal rates of PAH, catalase, and dehydrogenase activities
      of amended soil and accumulation of PAHs by vegetation were detected to
      investigate the differences of PAH dissipation in sludge-amended and compost
      amended soils. The initial PAH concentrations in three amended soils increased
      with the more addition of sludge or compost. After 126-day experiment, maximum
      PAH removal rates were observed in sludge-amended and compost-amended soils with
      PAH concentration of about 200 MUg kg-1. And the removal of PAHs showed better
      efficiencies in compost soil rather than in sludge soil. The more catalase
      activity and dehydrogenase activity of soil were obtained, respectively, in
      sludge soil and compost soil. The results indicated that the mechanism of PAH
      dissipation in two types of amended soils were different. The abundant amount of
      microorganism dominated PAH dissipation in sludge soils, and PAHs dissipated
      mainly caused of intense activity of microorganism in compost soils. In addition,
      PAH accumulation in tall fescue suggested that the transference approach of PAHs
      was from soil to the roots, and then accumulated in the shoots of tall fescue. It
      was prone to store up more PAHs in vegetation in the condition of high molar
      weight of PAHs, more biomass of vegetation, and heavy PAH concentration in soil.

PMID- 30302733
TI  - The trade-environment nexus in light of governance: a global potential.
AB  - The theme of paper is to explore the trade-environment relationship and the role
      of institutions for 117 countries from global standpoint and five regions: Sub
      Saharan, European, Middle East and North Africa, Asia and Pacific, and Latin
      America and Caribbean, using the panel data span 2002-2014. By considering the
      endogeneity problem, to validate the nature of trade-environment nexuses, we
      applied the GMM first difference model in two steps. Likewise, Dumitrescu-Hurlin
      panel causality analysis is employed to affirm the causal relationship among the
      concern variables. The empirical findings of this study validate that the overall
      trade is significantly good to environment for sample countries (117) of the
      entire World, Europe, Asia, and Pacific regions. In further assessment, we
      incorporate interactive terms of institutions with trade, scale effect, and scale
      technique effect. The estimated results confirm that institution is the
      persistent instrument for resolving the environmental problems. Furthermore, we
      find the evidence of inverted u shape EKC in overall selected sample of the
      World, Sub-Saharan, Europe, Asia, and Pacific regions. In contrast, there is no
      confirmation of inverted u shape EKC hypothesis in Middle East and North Africa
      regions. Similarly, no strong evidence of inverted u-shaped EKC hypothesis is
      observed in Latin-America and Caribbean region.

PMID- 30302732
TI  - Dysregulation of Sqstm1, mitophagy, and apoptotic genes in chronic exposure to
      arsenic and high-fat diet (HFD).
AB  - Arsenic (As) is a toxic and hazardous metalloid. Unfortunately, its presence in
      drinking water together with wrong nutritional patterns is associated with an
      increase in the occurrence of metabolic disorders in young people. Degradation of
      mitochondria is presented by a specific form of autophagy called mitophagy which
      is an important landmark leading to apoptosis during lipotoxicity. Lipotoxicity
      and cellular toxicity due to arsenic intake can lead to changes in mitophagy and
      apoptosis. The protein derived from SQSTM1 gene, also called p62, plays an
      important role in energy homeostasis in the liver, and it can contribute to the
      regulation of autophagic responses given its effect on signaling of mTOR, MAPK,
      and NF-KB. Consequently, changes in Sqstm1, mitophagy (BNIP3), and apoptotic
      (caspase 3) genes in the livers of NMRI mice were examined with the use of real
      time RT-PCR Array followed by exposure to an environmentally relevant and
      negligible cytotoxic concentration of arsenite (50 ppm) in drinking water while
      being fed with a high-fat diet (HFD) or low-fat diet (LFD) for 20 weeks (LFD-As
      and HFD-As groups). While LFD-As and HFD groups showed a decrease in BNIP3
      expression, a significant increase was observed in the HFD-As group. P62 gene
      showed downregulation in LFD-As and HFD groups, and upregeneration was observed
      in the HFD-As group. Caspase 3 showed increased expression as the key factor
      associated with apoptotic liver cell death in the three groups, with the highest
      value in HFD-As group. Overall, the changes observed in the expression of Sqstm1,
      BNIP3, and caspase 3 in this study can be related to the level of liver damage
      caused by exposure to arsenic and HFD and probably, BNIP3 pro-apoptotic protein
      is associated with an increased cell death due to HFD and As.

PMID- 30302734
TI  - Low-frequency electromagnetic treatment of oilfield produced water for reuse in
      agriculture: effect on water quality, germination, and plant growth.
AB  - Competing demand for high-quality fresh water for agricultural, industrial, and
      municipal uses has placed tremendous stress on water resources; irrigating crops
      with fresh water is expensive and unsustainable. Using unconventional water
      sources such as oilfield produced water (PW) and treating PW with physical
      treatment methods such as electromagnetic treatment may overcome water-limitation
      challenges. A germination experiment was conducted using treated and untreated PW
      to examine the effect on the germination of iron and clay cowpeas (ICCs) since
      germination is the stage at which plants are most sensitive to external factors
      and stresses. The results from the study showed that ICCs germinated when
      irrigated with higher salinity water that was treated using the electromagnetic
      technology. A plant growth study was also conducted to assess the effect of
      electromagnetic treatment of high-salinity PW on the growing ability and crop
      health of ICCs. A reduction in leaf area expansion rate, the first indicator of
      salt stress on plants, was observed. After 14 days, plants showed early signs of
      salt stress such as wilting, lightening in color, and reduction in leaf area.
      After 28 days, plants watered with higher salinity PW (21,475-42,950 mg/L total
      dissolved solids) died and plants watered with lower salinity PW (< 21,475 mg/L
      total dissolved solids) survived but grew smaller than plants irrigated using
      fresh water. Results from both experiments suggested a potential total dissolved
      solids limit of ICCs or electromagnetic technology (or both) between 4000 and
      10,000 mg/L. The results further suggested that while the electromagnetic
      technology did not have a strong effect on plant growth, high-salinity water
      might be treated for reuse in agriculture.

PMID- 30302735
TI  - Antifibrotics in liver disease: are we getting closer to clinical use?
AB  - The process of wound healing in response to chronic liver injury leads to the
      development of liver fibrosis. Regardless of etiology, the profound impact of the
      degree of liver fibrosis on the prognosis of chronic liver diseases has been well
      demonstrated. While disease-specific therapy, such as treatments for viral
      hepatitis, has been shown to reverse liver fibrosis and cirrhosis in both
      clinical trials and real-life practice, subsets of patients do not demonstrate
      fibrosis regression. Moreover, where disease-specific therapies are not
      available, the need for antifibrotics exists. Increased understanding into the
      pathogenesis of liver fibrosis sets the stage to focus on antifibrotic therapies
      attempting to: (1) Minimize liver injury and inflammation; (2) Inhibit liver
      fibrogenesis by enhancing or inhibiting target receptor-ligand interactions or
      intracellular signaling pathways; and (3) Promote fibrosis resolution. While no
      antifibrotic therapies are currently available, a number are now being evaluated
      in clinical trials, and their use is becoming closer to reality for select
      subsets of patients.

PMID- 30302737
TI  - Catch the ruler: concurrent validity and test-retest reliability of the ReacStick
      measures of reaction time and inhibitory executive function in older people.
AB  - BACKGROUND: Reduced cognitive function, particularly executive function (EF), is
      associated with an increased risk of falling in older people. We evaluated the
      utility of the ReacStick test, a clinical test of reaction time, and inhibitory
      EF developed, for young athletes, for fall-risk assessment in older people. AIMS:
      To evaluate the psychometric properties of ReacStick measures of reaction time
      and executive functioning in healthy community-dwelling older people. METHODS:
      140 participants (aged 77 +/- 5 years) underwent testing. Two test conditions
      simple and inhibitory go/no-go-provided measures of reaction time, recognition
      load (difference in reaction time between conditions), and go/no-go accuracy.
      Concurrent validity was evaluated against the conventional tests of reaction time
      and EF (simple hand reaction time, trail-making test, and Stroop colour test).
      Discriminant ability was determined for fall-risk factors (age, gender,
      physiological profile assessment, and fall history). Test-retest reliability
      after 1 week was evaluated in 30 participants. RESULTS: ReacStick reaction time
      correlated with tests of reaction time and EF, recognition load correlated with
      inhibitory EF, and go accuracy correlated with reaction time and inhibitory EF.
      No-go accuracy was not significantly correlated with any of the reaction time and
      EF tests. Test-retest reliability was good-to-excellent (ICC > 0.6) for all the
      outcomes. ReacStick reaction time discriminated between groups based on age,
      recognition load between genders, and no-go accuracy between retrospective
      fallers and non-fallers. DISCUSSION: An unavoidable time pressure may result in
      complementary information to the traditional measures. CONCLUSIONS: The ReacStick
      is a reliable test of reaction time and inhibitory EF in older people and could
      have value for fall-risk assessment.

PMID- 30302736
TI  - The Evolution of Estrogen Receptor Signaling in the Progression of Endometriosis
      to Endometriosis-Associated Ovarian Cancer.
AB  - To investigate changes in estrogen receptor alpha (ERalpha) signaling during
      progression of endometriosis to endometriosis-associated ovarian cancer (EAOC) as
      a driver of malignant transformation. We procured tissue samples of normal
      endometrium, endometriosis (benign, atypical, concurrent with EAOC), and EAOC. We
      evaluated expression of a 236-gene signature of estrogen signaling. ANOVA and
      unsupervised clustering were used to identify gene expression profiles across
      disease states. These profiles were compared to profiles of estrogen regulation
      in cancer models from the Gene Expression Omnibus (GEO). Gene Set Enrichment
      Analysis (GSEA) was performed to determine whether gene expression in EAOC was
      consistent with ERalpha activity. ANOVA revealed 158 differentially expressed
      genes (q < 0.05) and unsupervised clustering identified five distinct gene
      clusters. The estrogen signaling profile of EAOC was not consistent with
      activated ERalpha in pre-clinical models. Gene set enrichment analysis did not
      identify signatures of activated ERalpha in EAOC but instead identified
      expression patterns consistent with loss of ERalpha function and development of
      endocrine resistance. Gene expression data suggest that ERalpha signaling becomes
      inactivated throughout the progression of endometriosis to EAOC. The gene
      expression pattern in EAOC is more consistent with profiles of endocrine
      resistance.

PMID- 30302738
TI  - Intracytoplasmic azurophilic inclusions in prolymphocytes.

PMID- 30302739
TI  - Risk factors and survival impact of readmission after single-unit cord blood
      transplantation for adults.
AB  - Hospital readmissions have been used as a prognostic indicator for patients
      receiving allogeneic hematopoietic cell transplantation (HCT). However, the
      impact of readmission during early and mid-phase of cord blood transplantation
      (CBT) on long-term outcomes has not been fully investigated. We retrospectively
      analyzed 156 adult patients who received single-unit CBT in our institute. Among
      this cohort, thirteen patients (8%) were readmitted within 30 days after
      discharge, and 27 (17%) were readmitted within 90 days after discharge. The most
      common causes for readmission within 30 and 90 days of discharge were infection,
      chronic graft-versus-host disease, and relapse. Higher cryopreserved cord blood
      CD34+ cell count was only significantly associated with lower readmission within
      90 days after discharge. The probabilities of overall survival were significantly
      lower in patients readmitted within 90 days after discharge compared with those
      who were not readmitted within 90 days after discharge in univariate and
      multivariate analysis. These data suggest that readmission within 90 days after
      discharge may have a significant impact on long-term mortality after single-unit
      CBT.

PMID- 30302740
TI  - Anti-tissue factor pathway inhibitor (TFPI) therapy: a novel approach to the
      treatment of haemophilia.
AB  - Novel approaches to the treatment of haemophilia are needed due to the
      limitations of the current standard of care, factor replacement therapy.
      Aspirations include lessening the treatment burden and effectively preventing
      joint damage. Treating haemophilia by restoring thrombin generation may be an
      effective approach. A promising target for restoring thrombin generation is
      tissue factor pathway inhibitor (TFPI), a multivalent Kunitz-type serine protease
      inhibitor that regulates tissue factor-induced coagulation via factor Xa
      dependent feedback inhibition of the tissue factor-factor VIIa complex.
      Inhibition of TFPI reverts the coagulation process to a more primitive state
      evolutionarily, whilst regulation by other natural inhibitors is preserved. An
      aptamer and three monoclonal antibodies directed against TFPI have been
      investigated in clinical trials. As well as improving thrombin generation in the
      range associated with mild haemophilia, anti-TFPI therapies have the advantage of
      subcutaneous administration. However, the therapeutic window needs to be defined
      along with the potential for complications due to the novel mechanism of action.
      This review provides an overview of TFPI, its role in normal coagulation, the
      rationale for TFPI inhibition, and a summary of anti-TFPI therapies, previously
      or currently in development.

PMID- 30302741
TI  - Predicting Substance Use and Deviant Behavior from Prosociality and Sociability
      in Adolescents.
AB  - Social competence is commonly considered an important factor that impedes
      maladaptive development because individuals who lack adequate competence to
      direct or control their behaviors in social situations are likely to display
      problems. Despite the belief that social competence may be a multi-dimensional
      construct, existing research has not explored the unique contributions of its
      different aspects to development. The present two-wave longitudinal study
      examined relations of prosociality and sociability, two major aspects of social
      competence, with problem behaviors in a sample of adolescents. Peer assessment
      data on prosociality and sociability and self-report data on substance use and
      deviant behavior were obtained from a sample of adolescents in middle (N = 657,
      mean age = 13 years) and high (N = 675, mean age = 16 years) schools in China.
      The results showed that prosociality negatively predicted later problem
      behaviors, whereas sociability positively predicted later problem behaviors. In
      addition, gender and grade moderated the associations between sociability and
      problem behaviors. More specifically, the positive association between
      sociability and later substance use was significant for boys, but not for girls.
      Sociability was also more strongly associated with later substance use in middle
      school than in high school. The results indicate that prosociality and
      sociability may have different functional meanings in adolescent development and
      have implications for practical work with adolescents who display problem
      behaviors.

PMID- 30302742
TI  - Effect of Long-Term Exercise Training on lncRNAs Expression in the Vascular
      Injury of Insulin Resistance.
AB  - LncRNA microarray analysis was applied to investigate the exercise effect on the
      global differential expressions of lncRNA and mRNA in aorta endothelium in
      insulin resistance. Twenty-four male C57BL/6 J mice were randomly divided into
      three groups: control group (n = 8), high-fat diet group (n = 8), and high-fat
      diet plus exercise training group (n = 8). An lncRNA microarray analysis was
      applied to investigate the global differential expressions of lncRNA and mRNA in
      aorta endothelium among three groups and the results were further verified by
      qPCR. Hypergeometric distribution analysis was applied to reveal the possible
      signaling. Exercise might alleviate the vascular injury of IR via FR030200
      Col3A1, FR402720-Rnd1, and FR030200/FR402720-Rnd3 signalings in cytoskeletal
      rearrangement pathway; E2F1-FR030200/FR402720-Nnat and FR030200/ FR402720-Fam46a
      signalings in anti-inflammation pathway. This study identified a panel of
      dysregulated lncRNAs and mRNAs that might serve as potential biomarkers relevant
      to the vascular injury in insulin resistance induced by high-fat diet.

PMID- 30302743
TI  - Interleukin-1 Receptor-Like 1 (IL1R1) Levels Are Not Increased in Healthy
      Centenarians.

PMID- 30302744
TI  - Processes of Change for Colonoscopy: Limited Support for Use Among Navigated
      Latinos.
AB  - This study assessed the role of the processes of change (POC), a construct of the
      transtheoretical model, in colorectal cancer (CRC) screening among Latinos.
      Latinos participate in CRC screening less often and are diagnosed with CRC at a
      later stage than whites. POC items were administered to 344 English- and Spanish
      speaking Latinos at average risk for CRC who had not had a colonoscopy in the
      past 5 years and received a colonoscopy referral. POC were measured at three
      timepoints: following informed consent (T1) at time of referral, 2 weeks prior to
      scheduled colonoscopy (T2), and 1 month after scheduled colonoscopy (T3).
      Participants received patient navigation as part of a randomized controlled trial
      to promote screening colonoscopy. POC scores were examined for changes during the
      course of the intervention, and logistic regression models assessed the
      relationship between POC scores and CRC screening adherence. Total POC scores
      decreased between T1 and T2 (p = 0.03) but were unchanged between T1 and T3. CRC
      screening adherence was not significantly associated with POC scores or change in
      POC scores over time. The POC instrument was not found useful for predicting
      colonoscopy adherence among Latinos in conjunction with patient navigation. Total
      POC scores did not increase during a patient navigation intervention despite high
      colonoscopy completion rates.

PMID- 30302745
TI  - Membrane trafficking and exocytosis are upregulated in port wine stain blood
      vessels.
AB  - INTRODUCTION: Port wine stain (PWS) is characterized as a progressive dilatation
      of immature venule-like vasculatures which result from differentiation-impaired
      endothelial cells. In this study, we aimed to identify the major biological
      pathways accounting for the pathogenesis of PWS. METHODS: Sequential windowed
      acquisition of all theoretical fragment ion mass spectra (SWATH-MS) was used to
      identify differentially expressed proteins in PWS lesions, followed by
      confirmative studies with immunohistochemistry, immunoblot and transmission
      electron microscopy (TEM). RESULTS: 107 out of 299 identified proteins showed
      differential expressions in PWS lesions as compared to normal skin, mainly
      involving the functions of biosynthesis, membrane trafficking, cytoskeleton and
      cell adhesion/migration. The confirmative studies showed that expressions of
      membrane trafficking/exocytosis related proteins such as VAT1, IQGAP1, HSC70,
      clathrin, perlecan, spectrin alpha1 and GDIR1 were significantly increased in PWS
      blood vessels as compared to normal ones; while collagen subtypes 6A1 and 6A3
      were decreased in PWS skin. Furthermore, TEM studies showed there is a
      significant upregulation of extracellular vesicle exocytosis from PWS blood
      vessels as compared to control. CONCLUSIONS: The biological process of membrane
      trafficking and exocytosis is enhanced in PWS blood vessels. Our results imply
      that the extracellular vesicles released by lesional endothelial cells may act as
      potential intercellular signaling mediators to contribute to the pathogenesis of
      PWS.

PMID- 30302746
TI  - Arrangement of foot interosseous muscles in African great apes.
AB  - OBJECTIVES: The dorsal interossei of the human foot are arranged so that they
      abduct the digits around the second digit, while those of non-hominoid anthropoid
      primates are mostly arranged around the third or fourth digit. This is thought to
      relate to the medial shift in the functional axis, an essential modification in
      the evolution of the human foot. However, studies of the arrangement of
      interosseous muscles are relatively limited and there is some debate about their
      arrangement in great apes. In particular, some researchers claim that the
      interossei of chimpanzees are arranged around the second digit, whereas others
      claim that their foot axis lies on the third digit. MATERIALS AND METHODS: We
      examined the arrangement of the foot interosseous muscles in ten chimpanzees, one
      bonobo, and three gorillas. RESULTS: The interossei were arranged around the
      second digit in two chimpanzees, one bonobo, and one gorilla, whereas the third
      digit was the axis in the other specimens. DISCUSSIONS: The variation observed
      suggests that the arrangement of the interosseous muscles of the great apes is in
      a transitional condition from monkey-type to human-type. Considering that
      osteological and foot pressure research supports the idea that the foot axis is
      on the second digit in great apes, modification in the interosseous muscles
      appears to lag behind modification in the metatarsals and foot motion.

PMID- 30302747
TI  - Hair cortisol and childhood trauma predict psychological therapy response in
      depression and anxiety disorders.
AB  - OBJECTIVE: Around 30-50% of patients with depression and anxiety disorders fail
      to respond to standard psychological therapy. Given that cortisol affects
      cognition, patients with altered hypothalamic-pituitary-adrenal (HPA) axis
      functioning may benefit less from such treatments. To investigate this, reliable
      pretreatment cortisol measures are needed. METHOD: N = 89 outpatients with
      depression and anxiety disorders were recruited before undergoing therapy within
      an Improving Access to Psychological Therapies (IAPT) service. Three-month hair
      cortisol was determined, and the Childhood Trauma Questionnaire was administered.
      Patients were classified as responders if they showed significant decreases in
      depression (>= 6 points on the Patient Health Questionnaire) or anxiety (>= 5
      points on the Generalised Anxiety Disorder Scale). RESULTS: Non-responders in
      terms of depression (57%) had lower pretreatment hair cortisol concentrations (P
      = 0.041) and reported more physical abuse (P = 0.024), sexual abuse (P = 0.010)
      and total trauma (P = 0.039) when compared to responders. Non-responders in terms
      of anxiety (48%) had lower pretreatment hair cortisol (P = 0.027), as well as
      higher levels of emotional abuse (P = 0.034), physical abuse (P = 0.042) and
      total trauma (P = 0.048). CONCLUSION: If future research confirms hair cortisol
      to be a predictor of psychological therapy response, this may prove a useful
      clinical biomarker which identifies a subgroup requiring more intensive
      treatment.

PMID- 30302748
TI  - Countering infanticide: Chimpanzee mothers are sensitive to the relative risks
      posed by males on differing rank trajectories.
AB  - OBJECTIVES: Infanticide by males is common in mammals. According to the sexual
      selection hypothesis, the risk is inversely related to infant age because the
      older the infant, the less infanticide can shorten lactational amenorrhea; risk
      is also predicted to increase when an infanticidal male's chance of siring the
      replacement infant is high. Infanticide occurs in chimpanzees (Pan troglodytes),
      a species in which male dominance rank predicts paternity skew. Infanticidal male
      chimpanzees (if low-ranking) are unlikely to kill their own offspring, whereas
      those who are currently rising in rank, particularly when this rise is dramatic,
      have an increased likelihood of fathering potential future infants relative to
      any existing ones. Given that mothers should behave in ways that reduce
      infanticide risk, we predicted that female chimpanzees, and specifically those
      with younger, more vulnerable infants, would attempt to adjust the exposure of
      their infants to potentially infanticidal males. Specifically, mothers of young
      infants should reduce their association with adult males in general, and to a
      greater extent, with both low-ranking males and those rising in rank from a
      position where paternity of current infants was unlikely, to a rank where the
      probability of siring the next infant is significantly higher. We also
      investigated the alternative possibility that rather than avoiding all adult
      males, mothers would increase association with males of stable high rank on the
      basis that such males could offer protection against infanticide. MATERIALS AND
      METHODS: We examined data on female association patterns collected from the
      Budongo Forest, Uganda, during a period encompassing both relative stability in
      the male hierarchy and a period of instability with a mid-ranking male rising
      rapidly in rank. RESULTS: Using linear mixed models, we found that mothers
      reduced their association with the rank-rising male, contingent on infant age,
      during the period of instability. We also found evidence that females
      preferentially associated with a potential protector male during the high-risk
      period. DISCUSSION: Our results support the sexually selected hypothesis for
      infanticide and demonstrate that female chimpanzees are sensitive to the relative
      risks posed by adult males.

PMID- 30302749
TI  - Inhibitory effects of cycloastragenol on abdominal aortic aneurysm and its
      related mechanisms.
AB  - BACKGROUND AND PURPOSE: Abdominal aortic aneurysm (AAA) is a degenerative disease
      affecting human health, but there are no safe and effective medications for AAA
      therapy. Cycloastragenol (CAG), derived from Astragali Radix, has various
      pharmacological effects. However, whether CAG can protect against AAA remains
      elusive. In this study, we investigated whether CAG has an inhibitory effect on
      AAA and its related mechanism. EXPERIMENTAL APPROACH: The AAA mouse model was
      induced by incubating the abdominal aorta with elastase. CAG was administered by
      gavage at different doses beginning on the same day or 14 days after inducing AAA
      to explore its preventive or therapeutic effects respectively. The preventive
      effects of CAG on AAA were verified in another AAA mouse model induced by
      angiotensin II in ApoE-/- mouse. In vitro experiments were implemented on rat
      vascular smooth muscle cells (VSMCs) stimulated by TNF-alpha. KEY RESULTS:
      Compared to the control AAA model group, CAG (125 mg.kg-1 body weight day-1 )
      reduced the incidence of AAA, the dilatation of aorta and elastin degradation in
      media in both mouse models of AAA. CAG suppressed the inflammation, oxidation,
      phenotype switch and apoptosis in TNF-alpha-stimulated VSMCs, ameliorated the
      expression and activity of MMPs and decreased the activation of the ERK/JNK
      signalling pathway. CAG also inhibited the degradation of elastin in TNF-alpha
      stimulated VSMCs. CONCLUSION AND IMPLICATIONS: CAG presents protective effects
      against AAA through down-regulation of the MAPK signalling pathways and thus
      attenuates inflammation, oxidation, VSMC phenotype switch and apoptosis and the
      expression of MMPs as well as increasing elastin biosynthesis.

PMID- 30302750
TI  - Full face ingenol mebutate for actinic keratosis: patient perspective.

PMID- 30302751
TI  - Changing the Care System Long Before the "End Game".

PMID- 30302752
TI  - Introduction of a customised growth chart protocol increased detection of small
      for gestational age pregnancies in a tertiary Melbourne hospital.
AB  - BACKGROUND: Growth charts customised for maternal height, weight, ethnicity and
      parity have been proposed as more effective at detecting infants who are small
      for gestational age (SGA) than routine screening with symphysio-fundal height
      measurement alone. Our non-randomised, prospective cohort study assessed
      antenatal SGA detection rates in a general maternity cohort following the
      introduction of the Perinatal Institute's Growth Assessment Protocol (GAP)
      program (consisting of customised growth chart software for plotting symphysio
      fundal height, staff training and serial auditing). METHODS: The GAP program was
      implemented into the routine antenatal schedule of 882 women who delivered at The
      Royal Women's Hospital, Melbourne, during our study period. SGA detection was
      compared to 936 women from the same team who delivered prior to the intervention.
      Secondary outcomes assessed were infant gestation at birth and method of
      delivery, neonatal Apgar scores and admission to the Neonatal Intensive and
      Special Care nursery (NISC). RESULTS: Identification of SGA infants increased
      from 21% to 41% with the introduction of the GAP program (OR 2.6, 95% CI 1.3-4.9,
      P < 0.05). This was not associated with an increase in false-positive rates.
      Following the introduction of the GAP Program, SGA babies were more likely to be
      born by vaginal delivery (OR 2.7; 95% CI 1.4-5.1, P < 0.005). There was no
      overall increase in the induction of labour or caesarean delivery rates. Overall
      rates of admission to NISC were reduced. CONCLUSIONS: In our increasingly
      culturally heterogenous society, the use of the GAP program is a safe and
      potentially more sensitive tool for detecting in utero growth restriction.

PMID- 30302753
TI  - The steadily growing problem of lentigo maligna and lentigo maligna melanoma in
      Australia: Population-based data on diagnosis and management.
AB  - BACKGROUND/OBJECTIVES: There are limited population-based data documenting the
      incidence and management of lentigo maligna (LM) and invasive lentigo maligna
      melanoma (LMM). We report the data on occurrence and management of LM and LMM in
      an Australian population. METHODS: Prospective collection of incidence and
      clinician-reported management of melanoma in situ (MIS; n = 450, capped) and
      localised invasive melanoma (n = 3251) notified to the New South Wales Cancer
      Registry over 12-months in 2006-2007. RESULTS: The estimated annual incidence of
      all MIS was 27.0 per 100 000 (LM 12.2, non-LM MIS 5.9 and unclassified MIS 9.0).
      Patients with LM or LMM were on average approximately 10 years older than those
      with other melanoma subtypes (P < 0.001). The head and neck was the location of
      59% of LM, 44% of LMM and <20% of other melanoma subtypes (P < 0.001). The
      majority of LM and LMM were treated only by specialists. Diagnostic partial
      biopsies were more frequent for LM and LMM than for other melanoma subtypes, and
      primary care physicians were more likely than specialists to do a punch partial
      biopsy than a shave biopsy. The reported median definitive excision margin for LM
      was 5.0 mm compared with 7.2 mm for non-LM MIS (P = 0.001). CONCLUSIONS: In this
      Australian population, LM was twice as frequent as other types of MIS. Improved
      strategies for diagnosis and management are required.

PMID- 30302754
TI  - Confirmation of BRD4 haploinsufficiency role in Cornelia de Lange-like phenotype
      and delineation of a 19p13.12p13.11 gene contiguous syndrome.
AB  - Cornelia de Lange syndrome (CdLS) is a genetically and clinical heterogeneous
      condition characterized by congenital malformation, intellectual disability, and
      peculiar dysmorphic features. Recently, BRD4 (19p13.12) was proposed as a new
      critical gene associated with a mild CdLS because of a similar presentation of
      the patients carrying point mutations and of its involvement in the NIPBL
      pathway. Patients harboring a 19p interstitial deletion shared some physical
      features with BRD4 mutation carriers, which results in a more complex phenotype
      because of the involvement of several neighboring genes. We report a new 19p
      deletion in a patient clinically diagnosed as CdLS, partially overlapping with
      previously published cases with the aim to support the role of BRD4
      haploinsufficiency in a CdL-like phenotype and to improve the delineation of
      19p13.12p13.11 deletion as a new nonrecurrent gene contiguous syndrome, spanning
      GIPC1, NOTCH3, BRD4, AKAP8, AKAP8L, CASP14, and EPS15L1 genes. Previously
      described cases are reviewed, attempting to delineate a genotype-phenotype
      correlation.

PMID- 30302755
TI  - No evidence of sibling cooperation in the absence of parental care in Nicrophorus
      vespilloides.
AB  - Interactions among siblings fall on a continuum with competition and cooperation
      at opposite ends of the spectrum. Prior work on the burying beetle Nicrophorus
      vespilloides suggests that parental care shifts the balance between competition
      and cooperation by masking a density-dependent shift from cooperation to
      competition. However, these results should be interpreted with caution because
      they were based on correlational evidence for an association between larval
      density at dispersal and mean larval mass at dispersal. Here, we test for a
      causal effect of the initial density of larvae in a brood on the larvae's
      subsequent performance in the absence of care. We find no effect of the initial
      larval density on mean larval mass. Thus, our results provide no evidence for
      sibling cooperation in the absence of care in this species. However, using larval
      density at dispersal as a predictor of mean larval mass at dispersal, there was a
      significant correlation between larval density and mean larval mass. Our study
      highlights the importance of using experimental designs that exclude confounding
      effects due to shared environmental conditions that otherwise could be
      misinterpreted as evidence for sibling cooperation.

PMID- 30302756
TI  - Molecular pharmacology of GPCRs.
AB  - LINKED ARTICLES: This article is part of a themed section on Molecular
      Pharmacology of GPCRs. To view the other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc.

PMID- 30302757
TI  - Estrogen therapy associated with mechanical vibration improves bone
      microarchitecture and density in osteopenic female mice.
AB  - We investigated the effects of estrogen therapy (ET) associated with low
      intensity and high-frequency mechanical vibration (MV) on bone tissue in
      osteopenic female mice. Fifty 3-month-old female Swiss mice were ovariectomized
      (OVX) or sham-operated, and distributed after 4 months into the following groups,
      with 10 animals per group: Sham; Control, OVX + vehicle solution; MV, OVX + MV;
      ET, OVX + 17beta-estradiol; and MV + ET, OVX + MV and 17beta-estradiol. Both
      vehicle solution and 17beta-estradiol (10 MUg kg-1  day-1 ) were injected
      subcutaneously 7 days per week, and vibration (0.6 g, 60 Hz) was delivered 30 min
      per day, 5 days per week. Bone mineral density (BMD) and body composition were
      evaluated by densitometry at baseline and after 60 days of treatment when the
      animals were euthanized, and their femurs underwent histomorphometric and
      histochemical analyses. The Control group showed increased weight and fat
      percentage, while the ET and MV + ET groups showed increased lean mass but
      decreased fat percentage. At the end of the treatment period, the BMD decreased
      in Control, remained constant in Sham and MV, and increased in ET and MV + ET.
      The MV + ET group showed the greatest bone volume compared with Sham (129%),
      Control (350%), MV (304%) and ET (14%). No differences occurred in cortical
      thickness. The Control group showed the highest content of mature collagen
      fibers, while the MV + ET group showed the highest content of immature collagen
      fibers. In conclusion, ET plus MV was effective in improving bone quality in
      osteopenic female mice, and this improvement is associated with specific changes
      in trabecular but not cortical bone.

PMID- 30302758
TI  - Multiscale behavior analysis and molar behaviorism: An overview.
AB  - In the context of evolutionary theory, behavior is the interaction between the
      organism and its environment. Two implications follow: (a) behavior takes time;
      and (b) behavior is defined by its function. That behavior takes time implies
      that behavioral units are temporally extended patterns or activities. An activity
      functions as an integrated whole composed of parts that are themselves smaller
      scale activities. That behavior is defined by its function implies that behavior
      functions to change the environment in ways that promote reproductive success.
      Phylogenetically important events (PIEs) are enhanced or mitigated by activities
      they induce as a result of natural selection. Induction explains all the
      phenomena that have traditionally been explained by reinforcement. This
      multiscale view replaces discrete responses and contiguity with multiscale
      activities and covariance. A PIE induces operant activity as a result of
      covariance in the form of a feedback relation between the activity and the PIE. A
      signal (conditional inducer) induces PIE-induced activities as a result of
      covariance between the PIE and the signal. In an ontological perspective,
      behavior is a process, and an activity is a process individual. For example,
      ontological considerations clarify the status of delay and probability
      discounting. A true natural science of behavior is possible.

PMID- 30302759
TI  - Shifting preferences for choice-making opportunities through histories of
      differential reinforcer quality.
AB  - Children of both typical and atypical cognitive development tend to prefer
      contexts in which their behavior results in a choice of reinforcers rather than a
      single reinforcer, even when the reinforcer accessed is identical across
      conditions. The origin of this preference has been attributed speculatively to
      behavioral histories in which choice making tends to be associated with
      differentially beneficial outcomes. Few studies have evaluated this claim, and
      those that have, have yielded mixed results. We provided five preschool-aged
      children experiences in which choice-making and no-choice contexts were
      differentially associated with higher preference and larger magnitude
      reinforcers, and we assessed changes in their preference for choice and no-choice
      contexts in which outcomes were equated. These conditioning experiences resulted
      in consistent and replicable shifts in child preference, indicating that
      preference for choice is malleable through experience.

PMID- 30302760
TI  - High moisture extrusion of lupin protein: influence of extrusion parameters on
      extruder responses and product properties.
AB  - BACKGROUND: High moisture extrusion (HME) of lupin protein concentrate and
      isolate (50:50) mixture was performed by varying the extrusion parameters, such
      as barrel temperature (138-180  degrees C), water feed (40-68%) and screw speed
      (400-1800 rpm). The effect of extrusion parameters on extruder responses [die
      pressure, product temperature, torque and specific mechanical energy (SME)] and
      product properties [colour, cutting force, cooking yield, microstructure and in
      vitro protein digestibility (IVPD)] was evaluated. RESULTS: The multiple
      regression analysis of the results revealed that the water feed had a significant
      negative linear effect on the extruder responses considered, as well as on colour
      difference and cutting force of extrudates. Screw speed had a positive linear
      effect on product temperature, SME and cooking yield. Barrel temperature affected
      extruder responses and product properties to a lesser extent. Scanning electron
      microscopy showed that denser microstructure and higher number of fibre layers
      were created by increasing temperature and screw speed along with decreasing
      water feed. The results of IVPD of selected extrudates showed that the increase
      in barrel temperature decreased the IVPD, whereas the increase in water feed
      resulted in higher IVPD. The screw speed had no significant effect on IVPD.
      CONCLUSION: The study demonstrates that the use of lupin protein is feasible to
      produce meat analogues with HME which could enhance the possibilities to meet the
      growing protein demands for human consumption. (c) 2018 Society of Chemical
      Industry.

PMID- 30302761
TI  - Fluoroscopically guided wide-bore thoracostomy tube placement: Description of the
      technique and comparison to blind placement.
AB  - OBJECTIVE: To describe and compare fluoroscopic guidance for placement of wide
      bore thoracostomy tubes (FGTT) to traditional, blind placement of thoracostomy
      tubes (BPTT). STUDY DESIGN: Prospective clinical trial. ANIMALS: Twenty client
      owned dogs. METHODS: Dogs requiring medical management of pleural effusion
      received a BPTT, whereas dogs undergoing postoperative management of pneumothorax
      and/or pleural fluid after lateral thoracotomy received an FGTT. Time of
      placement, accuracy of positioning, radiation exposure, and complications were
      compared between groups. RESULTS: Initial placement of BPTT took a mean of 168
      seconds (range, 89-197), whereas adequate placement was radiographically
      confirmed at 20 minutes and 38 seconds (range, 7 minutes and 57 seconds to 39
      min). Initial placement of FGTT took a mean time of 108 seconds (range, 50-341, P
      = .17), and adequate placement was confirmed at 125 seconds (range, 50-341, P <
      .001). Major errors in placement requiring removal and replacement occurred in 2
      dogs for BPTT and in none for FGTT. Procedural complications did not differ
      between groups, and no postoperative complication occurred within the first 12
      hours after placement. Radiation entrance surface dose was lower in the BPTT
      group (P = .004), but stochastic radiation doses did not differ. CONCLUSION:
      Fluoroscopic guidance of wide-bore thoracostomy tubes accelerated the time to
      accurate tube placement and alleviated the requirement for removal and
      replacement in this population. Although use of fluoroscopy increased radiation
      entrance surface dose, the dose was not clinically significant. CLINICAL
      SIGNIFICANCE: Fluoroscopic guidance of wide-bore thoracostomy tubes should be
      considered as an alternative to traditional, blind placement.

PMID- 30302762
TI  - Prognostic value of noninvasive programmed stimulation in patients with
      implantable cardioverter defibrillator.
AB  - BACKGROUND: Implantable cardioverter defibrillator (ICD) offers an opportunity to
      examine vulnerability to ventricular tachycardia (VT) or ventricular fibrillation
      (VF) by performing noninvasive programmed ventricular stimulation (NIPS). Whether
      NIPS can predict VT/VF recurrences has not yet been established. PURPOSE: To
      examine the predictive value of NIPS for identification of patients with VT/VF
      recurrences. METHODS: The study group consisted of consecutive 105 ICD recipients
      included in the prospective NIPS-ICD study (ClinicalTrials ID: NCT02373306) (88
      males, age 65 +/- 11 years). The patients underwent NIPS using the protocol up to
      three premature extrastimuli at 600-500- and 400-ms drive cycle lengths. The
      endpoint of NIPS was induction of sustained VT or VF or completion of the
      protocol. RESULTS: VT/VF was induced in 29 (27.6%) patients. During a 12-month
      follow-up NIPS-inducible patients had significantly more frequently appropriate
      ICD therapy than noninducible patients (17% vs 4%, P = 0.023). NIPS-induced VT/VF
      had a sensitivity of 63%, specificity of 75%, positive predictive value of 17%,
      and negative predictive value of 96% for identification of patients with future
      VT/VF. Apart from NIPS, age >= 65 years, QRS duration, treatment with angiotensin
      converting enzyme, history of coronary artery bypass grafting, history of VT/VF
      prior to NIPS, and prior appropriate ICD therapy were also associated with VT/VF
      recurrences. Multivariate analysis showed that, together with QRS duration, NIPS
      result was an independent predictor of future VT/VF. Predictive value of NIPS was
      significantly higher in ischemic than nonischemic patients. CONCLUSIONS: NIPS
      result is associated with future VT/VF. Noninducibility at NIPS identifies those
      patients with high accuracy who will have uneventful follow-up.

PMID- 30302763
TI  - Investigation into the causes of aspirin resistance in healthy dogs.
AB  - Antiplatelet effects of acetylsalicylic acid (ASA, aspirin) may be poor in some
      individuals. Additionally, no method exists for predicting poor ASA response
      (resistance) in individual dogs. This study's main objective was to determine
      whether poor ASA response results from pharmacodynamic or pharmacokinetic causes.
      ASA concentrations causing 50% inhibition of platelet aggregation (in vitro IC50)
      were determined using whole blood collected from 21 drug-free healthy dogs to
      evaluate intrinsic sensitivity of platelets to ASA. Dogs were then administered
      ASA at 4 mg/kg once orally. Percent decrease in platelet aggregation from
      baseline, and plasma ASA and salicylic acid (SA) concentrations (expressed as AUC
      values) were measured for up to 3 hr. By 3 hr, 13/21 (62%) dogs showed >50%
      aggregation inhibition, while 8/21 (38%) dogs showed <50% inhibition. Aggregation
      inhibition values were negatively correlated with in vitro IC50 values (Rs = 
      0.49; p = 0.028) and positively correlated with ASA concentrations (Rs = 0.48; p
      = 0.03). Furthermore, ASA concentrations were strongly negatively correlated (Rs
      = -0.88; p < 0.001) with SA/ASA concentration ratios, an index of ASA metabolism
      to SA by esterase enzymes. Multiple linear regression analysis indicated that 59%
      (p < 0.001) of interindividual variability in aggregation inhibition was
      explained by in vitro IC50 values (29% of variability) and ASA concentrations
      (29% of variability). Consequently, poor in vivo ASA response in these dogs
      resulted from both pharmacodynamic (decreased platelet sensitivity) and
      pharmacokinetic (lower ASA concentrations) causes. Lower ASA concentrations may
      be explained by reduced bioavailability associated with higher esterase
      activities.

PMID- 30302764
TI  - Vancomycin hemodialysis: Clearance differences between high-flux hemodialysis and
      on-line hemodiafiltration.
AB  - The aim of this study was to analyze the differences between vancomycin clearance
      (Kd) with high-flux hemodialysis (HFHD) and on-line hemodiafiltration (OL-HDF).
      The OL-HDF therapy combined the diffusion and convective transport of solutes. To
      compare the Kd, a vancomycin loading dose of 1 g was administered intravenously
      post-dialysis to 11 chronic and anuric (<100 mL/24 h) hemodialysis patients,
      undergoing HFHD and post-dilutional OL-HDF in consecutive therapies. Additional
      doses of 0.5 g were administered after 45 minutes at the end of each dialysis
      therapy during antibiotic treatment. Blood samples were drawn from arterial and
      venous lines at the start of hemodialysis sessions and at the first, second,
      third, and fourth hours. Additional samples were drawn at 15, 30, and 45 minutes
      after the end of dialysis therapy. Vancomycin plasma concentration, blood urea
      nitrogen (BUN), creatinine, and beta2 -microglobulin were measured. The patients'
      hydration status was evaluated by bioimpedance analysis. The mean of vancomycin
      dialyzer clearance (Kddc ) calculated was 110.8 +/- 15 mL/min with HFHD and 146.8
      +/- 13.8 mL/min with OL-HDF (P = 0.025). Significant differences were also
      obtained for beta2 -microglobulin clearance, Kddc 72.6 +/- 15.4 mL/min with HFHD
      and 113.4 +/- 24.2 mL/min with OL-HDF (P = 0.012), whereas no differences were
      found for BUN or creatinine. Additionally, to analyze differences between HFHD
      and OL-HDF, a variable volume dual pool mathematical model was developed to
      estimate the body clearance (Kdbc ), extraction mass (Me ), and inter-compartment
      mass-transfer coefficient (K12 ) of each molecule. A higher vancomycin Kddc with
      OL-HDF produced by convection improved removal of antibiotic; this can compromise
      achieving a therapeutic concentration target. We recommended evaluating increased
      loading doses of vancomycin and avoiding administration during OL-HDF to assure
      adequate treatment.

PMID- 30302765
TI  - Chrysin leads to cell death in endometriosis by regulation of endoplasmic
      reticulum stress and cytosolic calcium level.
AB  - Chrysin is a natural compound derived from honey, propolis, or passion flowers
      and has many functional roles, such as antiinflammatory and antiangiogenesis
      effects. Although endometriosis is a benign gynecological disease, there is a
      need to identify the pathology and develop a therapy for endometriosis.
      Elucidating the biological mechanism of chrysin on endometriosis will improve the
      understanding of endometriosis. In this study, we confirmed the apoptotic effects
      of chrysin in human endometriotic cells using End1/E6E7 (endocervix-derived
      endometriotic cells) and VK2/E6E7 (vaginal mucosa-derived epithelial
      endometriotic cells). The results showed that chrysin suppressed the
      proliferation of endometriosis and induced programmed cell death through changing
      the cell cycle proportion and increasing the cytosolic calcium level and
      generation of reactive oxygen species. In addition, chrysin activated endoplasmic
      reticulum (ER) stress by stimulating the unfolded protein response proteins,
      especially the 78-kDa glucose-regulated protein-PRKR-like ER kinase (PERK)
      eukaryotic translation initiation factor 2alpha (eIF2alpha) pathway in both
      endometriotic cell lines. Furthermore, chrysin inactivated the intracellular
      phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT)
      signaling pathway in a dose-dependent manner. Collectively, the results of this
      study indicated that chrysin induced programmed cell death by activating the ER
      stress response and inactivating the PI3K signaling pathways in human
      endometriotic cells.

PMID- 30302766
TI  - Chitosan-glucose Maillard reaction products and their preservative effects on
      fresh grass carp (Ctenopharyngodon idellus) fillets during cold storage.
AB  - BACKGROUND: A decreasing freshness occurrs in Ctenopharyngodon (C.) idellus
      during post-mortem storage. In the present study, chitosan-glucose Maillard
      reaction products (CG-MRPs) were prepared by heating chitosan and glucose at
      different reaction temperatures and then used for preserving the freshness and
      quality of C. idellus fillets during cold storage (4  degrees C). RESULTS: High
      temperature enhanced the chitosan-glucose Maillard reaction and promoted the
      accumulation of melanoidins and intermediate compounds. The reducing power of CG
      MRPs increased with an increasing reaction temperature. CG-MRPs inhibited the
      microbial growth rate and retarded the oxidation of proteins, lipids and
      nucleotides in C. idellus fillets by suppressing total bacterial count, total
      volatile basic nitrogen, thiobarbituric acid reactive substances and K values
      during cold storage. Furthermore, CG-MRPs prolonged shelf-life. The fillets
      treated with the CG-MRPs prepared at 120  degrees C showed an especially longer
      shelf-life (7 days). The preservative effect of CG-MRPs on fillets was the result
      of antibacterial components (melanoidins, reductone and furfural) in CG-MRPs and
      a reducing power against the oxidative degradation of proteins, nucleotides and
      lipids in C. idellus fillets. CONCLUSION: The present study demonstrates that,
      for C. idellus fillets, treatment with CG-MRPs prepared at 120  degrees C for 40
      min could be a feasible approach for maintaining the freshness of C. idellus
      fillets and prolonging shelf-life during cold storage. (c) 2018 Society of
      Chemical Industry.

PMID- 30302767
TI  - High intensity focused electromagnetic therapy evaluated by magnetic resonance
      imaging: Safety and efficacy study of a dual tissue effect based non-invasive
      abdominal body shaping.
AB  - OBJECTIVES: This study introduces an initial evaluation of a novel High-Intensity
      Focused Electromagnetic (HIFEM) technology. The primary goal is to quantify any
      effects the treatments may have on abdominal tissues, as well as to establish
      hypotheses for future research of this technology. METHODS: Twenty-two patients
      received four abdominal treatments using the EMSCULPT device (BTL Industries
      Inc., Boston, MA). Anthropometric evaluations were recorded and digital
      photographs were taken at baseline, at 2 months, and at 6 months post-treatments.
      The MRI without contrast determined by vertertebras T12 and S1 (FIESTA and FSPRG
      sequences) was used to measure dimensions in coronal cross-sectional images of
      abdominal muscle and fatty tissues, in order to assess any anatomical changes
      induced by the application. RESULTS: Analysis of the same MRI slices verified by
      tissue artefacts showed a statistically significant (all P < 0.0001) average
      18.6% reduction of adipose tissue thickness, 15.4% increase in rectus abdominis
      muscle thickness, and 10.4% reduction in rectus abdominus separation (diastasis
      recti) as measured from the medial border of the muscle 2 months post-treatment.
      More significant improvements were observed in patients with BMI 18.5-24.9
      (classified as "normal"). MRI data from 6-month follow-up suggest the changes can
      be preserved in longer term. Tape measurements showed on average 3.8 cm
      subumbilical circumference reduction. The weight of the subjects did not change
      significantly (average -0.5 lb; P > 0.05). No adverse events were reported.
      CONCLUSIONS: MRI, considered as a highly precise diagnostic method, revealed
      simultaneous muscle growth, fat reduction and reduced abdominal separation at 2
      months and at 6 months post treatments, unrelated with dieting. Further research
      should investigate the exact physiological processes which stand behind the
      tissue changes observed in this study. Lasers Surg. Med. (c) 2018 The Authors.
      Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

PMID- 30302768
TI  - Design and psychometric testing of instruments to measure qualified intensive
      care nurses' attitudes toward obese intensive care patients.
AB  - The purpose of this pilot study was to design and test research instruments to
      measure qualified intensive care nurses' implicit and explicit attitudes and
      behavioral intentions toward obese intensive care patients. In previous studies
      researchers have demonstrated that some health professionals hold negative
      attitudes toward obese patients; however, little is known about qualified
      intensive care nurses' attitudes toward these patients. Our cross-sectional pilot
      study involved Implicit Association Tests, the Anti-fat Attitude questionnaire,
      an explicit bias scale comprising ratings of explicit beliefs and feelings,
      assessment of behavioral intentions based on vignettes, and demographic
      questions. Thirty qualified intensive care nurses from a general intensive care
      unit in Norway (80% female; age range 31-62 years) completed the study. Nurses
      reported implicit and explicit preferences for thin over thick patients and found
      obese patients lazier than normal-weight patients. Measures of behavioral
      intentions and anti-fat attitudes were reliable. Generally, the nurses intended
      to help obese patients immediately. Nevertheless, explicit anti-fat attitudes
      (rho = -0.49) as well as implicit anti-obese stereotypes (rho = -0.40) were
      negatively correlated with such intentions. Data supported satisfactory face
      validity, and convergent and discriminant validity within and between implicit
      and explicit attitudes and stereotypes. The set of research instruments were
      reliable, valid, and suitable tools to measure qualified intensive care nurses'
      implicit and explicit attitudes; however, the present findings need to be
      replicated in a larger-scale study.

PMID- 30302769
TI  - Apoyo con Carino (support with caring): RCT protocol to improve palliative care
      outcomes for Latinos with advanced medical illness.
AB  - Latinos are more likely to experience uncontrolled pain, and institutional death,
      and are less likely to engage in advance care planning. Efforts to increase
      access to palliative care must maximize primary palliative care and community
      based models to meet the ever-growing need in a culturally sensitive and
      congruent manner. Patient navigator interventions are community-based, culturally
      tailored models of care that have been successfully implemented to improve
      disease prevention, early diagnosis, and treatment. We have developed a patient
      navigation intervention to improve palliative care outcomes for seriously ill
      Latinos. We describe the protocol for a National Institute of Nursing Research
      funded randomized controlled trial designed to determine the effectiveness of the
      manualized patient navigator intervention. We aim to enroll 240 Latino adults
      with non-cancer, advanced medical illness from both urban and rural clinical
      sites. Participants will be randomized to the intervention group (five palliative
      care patient navigator visits plus bilingual educational materials) or control
      group (usual care plus bilingual educational materials). Outcomes include quality
      of life (Functional Assessment of Chronic Illness Therapy), advance care planning
      (Advance Care Planning Engagement survey), pain (Brief Pain Inventory), symptom
      management (Edmonton Symptom Assessment Scale-revised), hospice utilization, and
      cost and utilization of healthcare resources. This culturally tailored, evidence
      based, theory-driven, innovative patient navigation intervention has significant
      potential to improve palliative care for Latinos, and facilitate health equity in
      palliative and end-of-life care.

PMID- 30302770
TI  - Laser threshold and cell damage mechanism for intravascular photoacoustic
      imaging.
AB  - OBJECTIVES: Intravascular photoacoustic (IVPA) imaging is being developed to
      image atherosclerotic plaques, a leading cause of morbidity and mortality in the
      United States. However, the safety of this imaging modality, which requires
      repeated irradiation with short laser pulses, has not yet been investigated. This
      study has two objectives. First, determine in vitro the limit of cumulative
      fluence that can be applied to cells before death at IVPA relevant wavelengths.
      Second, evaluate if high single pulse fluences are a potential cause of cell
      death during IVPA imaging. MATERIALS AND METHODS: Experiments were conducted
      using endothelial cells, macrophages, and smooth muscle cells. The cumulative
      fluence experiments were conducted at 1064 and 1197 nm, using a high pulse
      repetition frequency laser. Cells were irradiated with a wide range of cumulative
      fluences and evaluated for cell death. The thresholds for death were compared to
      the maximum expected clinical cumulative fluence. To evaluate the effect of
      single pulse fluences, cells were irradiated at 1064, 1210, and 1720 nm. Light
      was delivered at a range of pulse energies to emulate the fluences that cells
      would be exposed to during clinical IVPA imaging. RESULTS: At 1064 nm, all three
      cell types remained viable at cumulative fluences above the maximum expected
      clinical cumulative fluence, which is calculated based on common IVPA imaging
      protocols. At 1197 nm, cells were viable near or just below the maximum expected
      clinical cumulative fluence, with some cell type to cell type variation. All
      three cell types remained viable after irradiation with high single pulse
      fluences at all three wavelengths. CONCLUSION: The cumulative fluence experiments
      indicate that safety considerations are likely to put constraints on the amount
      of irradiation that can be used in IVPA imaging protocols. However, this study
      also indicates that it will be possible to use IVPA imaging safely, since
      cumulative fluences could be reduced by as much as two orders of magnitude below
      the maximum expected clinical cumulative fluence by varying the imaging protocol,
      albeit at the expense of image quality. The single pulse fluence experiments
      indicate that cell death from single pulse fluence is not likely during IVPA
      imaging. Thus, future studies should focus on heat accumulation as the likely
      mechanism of tissue damage. Lasers Surg. Med. (c) 2018 Wiley Periodicals, Inc.

PMID- 30302771
TI  - The interaction effect between vibrations and temperature simulating truck
      transport on the flavor stability of beer.
AB  - BACKGROUND: Beer flavor stability is important to brewers as a result of the
      increased global demand for beer. Increasing export leads to prolonged periods of
      transportation and storage and causes fresh flavor deterioration. Therefore, the
      present study examined the effect of different temperatures in combination with
      vibrations on beer quality. Beer was exposed to vibrations (50 Hz, 15 m s-2 ,
      simulating transport) at 5, 30 and 45  degrees C for 22, 38 and 90 h and (for
      half the samples) aged for 60 days at 30  degrees C. RESULTS: The results
      obtained indicated decreased oxygen concentrations as a result of an elevated
      temperature and vibrations. There was no effect (P > 0.05) on color and a limited
      effect of temperature and vibrations on iso-alpha-acids. The parameters
      temperature and vibrations have a significant influence (P < 0.05) on aldehyde
      concentrations, namely total aldehydes, and especially '2-methylpropanal', '2
      methylbutanal' and 'furfural'. CONCLUSION: The impact of vibrations on the
      aldehydes concentrations was substantial when subjected to an elevated
      temperature. Furthermore, a forced aging test of shorter duration than
      traditional methods might be developed. (c) 2018 Society of Chemical Industry.

PMID- 30302772
TI  - The multifaceted role of autophagy in cancer and the microenvironment.
AB  - Autophagy is a crucial recycling process that is increasingly being recognized as
      an important factor in cancer initiation, cancer (stem) cell maintenance as well
      as the development of resistance to cancer therapy in both solid and
      hematological malignancies. Furthermore, it is being recognized that autophagy
      also plays a crucial and sometimes opposing role in the complex cancer
      microenvironment. For instance, autophagy in stromal cells such as fibroblasts
      contributes to tumorigenesis by generating and supplying nutrients to cancerous
      cells. Reversely, autophagy in immune cells appears to contribute to tumor
      localized immune responses and among others regulates antigen presentation to and
      by immune cells. Autophagy also directly regulates T and natural killer cell
      activity and is required for mounting T-cell memory responses. Thus, within the
      tumor microenvironment autophagy has a multifaceted role that, depending on the
      context, may help drive tumorigenesis or may help to support anticancer immune
      responses. This multifaceted role should be taken into account when designing
      autophagy-based cancer therapeutics. In this review, we provide an overview of
      the diverse facets of autophagy in cancer cells and nonmalignant cells in the
      cancer microenvironment. Second, we will attempt to integrate and provide a
      unified view of how these various aspects can be therapeutically exploited for
      cancer therapy.

PMID- 30302773
TI  - Population pharmacokinetics of itraconazole solution after a single oral
      administration in captive lesser flamingos (Phoeniconaias minor).
AB  - Aspergillosis is an infectious, non-contagious fungal disease of clinical
      importance in flamingo collections. Itraconazole is an antifungal drug commonly
      used in the treatment and prophylaxis of avian aspergillosis. Studies have shown
      that dosage regimes in birds vary based on different itraconazole presentation
      and administration methods. This investigation used a population pharmacokinetic
      approach to study itraconazole in lesser flamingos. Itraconazole was administered
      orally at 10 mg/kg to 17 flamingos. A sparse blood sampling was performed on the
      subjects, and samples were collected at 1, 2, 3, 5, 8, 12, 16, 21, and 24 hr post
      drug administration. Twelve flamingos were sampled three times, three birds bled
      twice and two sampled once. Itraconazole in plasma was quantified using high
      pressure liquid chromatography (HPLC). A one-compartment pharmacokinetic model
      with first order absorption was fitted to the data using nonlinear mixed effects
      modeling (NLME) to determine values for population parameters. We identified a
      long half-life (T1/2) of more than 75 hr and a maximum plasma concentration (CMAX
      ) of 1.69 ug/ml, which is above the minimal inhibitory concentrations for
      different aspergillus isolates. We concluded that plasma drug concentrations of
      itraconazole were maintained in a population of flamingos above 0.5 ug/ml for at
      least 24 hr after a single oral dose of 10 mg/kg of itraconazole solution.

PMID- 30302774
TI  - Synthesis, carbonic anhydrase inhibitory activity and antioxidant activity of
      some 1,3-oxazine derivatives.
AB  - Hit, Lead & Candidate Discovery A series of 1-(6-methyl-2-substituted phenyl-4
      thioxo-4H-1,3-oxazin-5-yl)ethanones (3a-n) were synthesized by the reaction of
      benzoyl isothiocyanates with active methylene compound acetylacetone in the
      presence of triethyl amine in a one-pot process. The structures of the products
      were elucidated by elemental analyses, FT-IR, 1 H NMR, 13 C NMR, and mass
      spectroscopy. These new 1,3-oxazine derivatives were evaluated for their
      inhibitory activity against carbonic anhydrase II. Results for in vitro assay
      revealed that compound 3b having 4-methoxy phenyl moiety was the most potent
      inhibitor with IC50 value of 0.144 +/- 0.008 MUM. It exhibited higher enzyme
      inhibitory activity as compared to the standard acetazolamide (IC50  = 0.997 +/-
      0.061 MUM). The compounds 3c, 3h, and 3n also displayed superior inhibitory
      activities compared to the rest of the synthesized oxazine derivatives. The
      radical scavenging activity of oxazine derivatives was also performed and it was
      found that compounds showed moderate antioxidant activity. Lipinski rule
      confirmed the therapeutic potential of the synthesized compounds. Molecular
      docking studies were also performed to further understand the binding affinity of
      these compounds with PDBID 1V9E which confirmed that the synthesized derivatives
      bind in the active binding site of the target protein. Based upon our results, it
      is proposed that compound 3b may serve as a lead structure to design more potent
      carbonic anhydrase inhibitors.

PMID- 30302775
TI  - Pharmacokinetics of levofloxacin after single intravenous, oral and subcutaneous
      administration to dogs.
AB  - The pharmacokinetic properties of the fluoroquinolone levofloxacin (LFX) were
      investigated in six dogs after single intravenous, oral and subcutaneous
      administration at a dose of 2.5, 5 and 5 mg/kg, respectively. After intravenous
      administration, distribution was rapid (T1/2dist 0.127 +/- 0.055 hr) and wide as
      reflected by the volume of distribution of 1.20 +/- 0.13 L/kg. Drug elimination
      was relatively slow with a total body clearance of 0.11 +/- 0.03 L kg-1  hr-1 and
      a T1/2 for this process of 7.85 +/- 2.30 hr. After oral and subcutaneous
      administration, absorption half-life and Tmax were 0.35 and 0.80 hr and 1.82 and
      2.82 hr, respectively. The bioavailability was significantly higher (p ? 0.05)
      after subcutaneous than oral administration (79.90 vs. 60.94%). No statistically
      significant differences were observed between other pharmacokinetic parameters.
      Considering the AUC24 hr /MIC and Cmax /MIC ratios obtained, it can be concluded
      that LFX administered intravenously (2.5 mg/kg), subcutaneously (5 mg/kg) or
      orally (5 mg/kg) is efficacious against Gram-negative bacteria with MIC values of
      0.1 MUg/ml. For Gram-positive bacteria with MIC values of 0.5 MUg/kg, only SC and
      PO administration at a dosage of 5 mg/kg showed to be efficacious. MIC-based
      PK/PD analysis by Monte Carlo simulation indicates that the proposed dose
      regimens of LFX, 5 and 7.5 mg/kg/24 hr by SC route and 10 mg/kg/24 hr by oral
      route, in dogs may be adequate to recommend as an empirical therapy against S.
      aureus strains with MIC <= 0.5 MUg/ml and E. coli strains with MIC values <=0.125
      MUg/ml.

PMID- 30302776
TI  - Pharmacokinetics of monoester-diterpenoid alkaloids in myocardial infarction and
      normal rats after oral administration of Sini decoction by microdialysis combined
      with liquid chromatography-tandem mass spectrometry.
AB  - Monoester-diterpenoid alkaloids are the main bioactive components of Sini
      decoction, which is a well-known traditional Chinese medicine formula for the
      treatment of myocardial infarction (MI) and heart failure in China. In this work,
      an ultra-high-performance liquid chromatography-mass spectrometry combined with
      microdialysis method was successfully established and applied for investigating
      for the first time comparative plasma pharmacokinetics of three monoester
      diterpenoid alkaloids (benzoylmesaconitine, benzoylaconitine and
      benzoylhypacoitine) in normal and MI rats after oral administration of Sini
      decoction. The statistical results of pharmacokinetic parameters demonstrated
      that benzoylmesaconitine, benzoylaconitine and benzoylhypacoitine showed lower
      peak concentration, longer half-life, smaller area under the concentration-time
      curve, slower clearance, time to peak concentration and mean residence time in MI
      rats than in normal rats (p < 0.05), which indicated that monoester-diterpenoid
      alkaloids exhibited lower systemic exposure and slower elimination in the MI
      rats. The results provided the experimental basis for understanding the metabolic
      fate and therapeutic effects of Sini decoction.

PMID- 30302777
TI  - The role of the unfolded protein response in cancer progression: From oncogenesis
      to chemoresistance.
AB  - Tumour cells endure both oncogenic and environmental stresses during cancer
      progression. Transformed cells must meet increased demands for protein and lipid
      production needed for rapid proliferation and must adapt to exist in an oxygen-
      and nutrient-deprived environment. To overcome such challenges, cancer cells
      exploit intrinsic adaptive mechanisms such as the unfolded protein response
      (UPR). The UPR is a pro-survival mechanism triggered by accumulation of unfolded
      or misfolded proteins in the endoplasmic reticulum (ER), a condition referred to
      as ER stress. IRE1, PERK and ATF6 are three ER anchored transmembrane receptors.
      Upon induction of ER stress, they signal in a coordinated fashion to re-establish
      ER homoeostasis, thus aiding cell survival. Over the past decade, evidence has
      emerged supporting a role for the UPR in the establishment and progression of
      several cancers, including breast cancer, prostate cancer and glioblastoma
      multiforme. This review discusses our current knowledge of the UPR during
      oncogenesis, tumour growth, metastasis and chemoresistance.

PMID- 30302778
TI  - Lip-to-nose flap for nasal plane reconstruction in dogs: A cadaveric and in vivo
      feasibility study.
AB  - OBJECTIVE: To describe a local interpolation flap based on the upper lip for the
      reconstruction of the dorsal aspect of the nasal plane in dogs. STUDY DESIGN: Ex
      vivo and in vivo case report. ANIMALS: A 2-year-old medium-sized spayed female
      mixed-breed dog and a canine cadaver of a medium-sized mixed-breed dog. METHODS:
      A dorsal defect of the nasal plane of uncertain origin in a dog was reconstructed
      with a unilateral interpolation flap obtained from the caudal upper lip skin and
      mucosa (lip-to-nose flap). The procedure was first performed in a cadaveric model
      to assess its feasibility. RESULTS: The lip-to-nose flap allowed the
      reconstruction of a dorsal nasal plane defect with a satisfactory cosmetic
      outcome. The incorporation of the labial mucosa guaranteed a complete and
      uncomplicated wound healing of the flap; a small area of necrosis occurred at the
      donor site, which resolved in a few days. CONCLUSION: The use of a lip-to-nose
      flap was feasible in these 2 medium-sized dogs and led to satisfactory cosmetic
      outcome. CLINICAL SIGNIFICANCE: A lip-to-nose flap may be considered to
      reconstruct dorsal nasal plane defects in dogs and allows for a cosmetic outcome.

PMID- 30302779
TI  - Microbial esterases and ester prodrugs: An unlikely marriage for combating
      antibiotic resistance.
AB  - The rise of antibiotic resistance necessitates the search for new platforms for
      drug development. Prodrugs are common tools for overcoming drawbacks typically
      associated with drug formulation and delivery, with ester prodrugs providing a
      classic strategy for masking polar alcohol and carboxylic acid functionalities
      and improving cell permeability. Ester prodrugs are normally designed to have
      simple ester groups, as they are expected to be cleaved and reactivated by a wide
      spectrum of cellular esterases. However, a number of pathogenic and commensal
      microbial esterases have been found to possess significant substrate specificity
      and can play an unexpected role in drug metabolism. Ester protection can also
      introduce antimicrobial properties into previously nontoxic drugs through
      alterations in cell permeability or solubility. Finally, mutation to microbial
      esterases is a novel mechanism for the development of antibiotic resistance. In
      this review, we highlight the important pathogenic and xenobiotic functions of
      microbial esterases and discuss the development and application of ester prodrugs
      for targeting microbial infections and combating antibiotic resistance. Esterases
      are often overlooked as therapeutic targets. Yet, with the growing need to
      develop new antibiotics, a thorough understanding of the specificity and function
      of microbial esterases and their combined action with ester prodrug antibiotics
      will support the design of future therapeutics.

PMID- 30302780
TI  - Doubly robust estimation of the weighted average treatment effect for a target
      population.
AB  - The weighted average treatment effect is a causal measure for the comparison of
      interventions in a specific target population, which may be different from the
      population where data are sampled from. For instance, when the goal is to
      introduce a new treatment to a target population, the question is what efficacy
      (or effectiveness) can be gained by switching patients from a standard of care
      (control) to this new treatment, for which the average treatment effect for the
      control estimand can be applied. In this paper, we propose two estimators based
      on augmented inverse probability weighting to estimate the weighted average
      treatment effect for a well-defined target population (ie, there exists a
      predefined target function of covariates that characterizes the population of
      interest, for example, a function of age to focus on elderly diabetic patients
      using samples from the US population). The first proposed estimator is doubly
      robust if the target function is known or can be correctly specified. The second
      proposed estimator is doubly robust if the target function has a linear
      dependence on the propensity score, which can be used to estimate the average
      treatment effect for the treated and the average treatment effect for the
      control. We demonstrate the properties of the proposed estimators through
      theoretical proof and simulation studies. We also apply our proposed methods in a
      comparison of glucagon-like peptide-1 receptor agonists therapy and insulin
      therapy among patients with type 2 diabetes, using the UK Clinical Practice
      Research Datalink data.

PMID- 30302781
TI  - Model averaging for robust extrapolation in evidence synthesis.
AB  - Extrapolation from a source to a target, eg, from adults to children, is a
      promising approach to utilize external information when data are sparse. In the
      context of meta-analyses, one is commonly faced with a small number of studies,
      whereas potentially relevant additional information may also be available. Here,
      we describe a simple extrapolation strategy using heavy-tailed mixture priors for
      effect estimation in meta-analysis, which effectively results in a model
      averaging technique. The described method is robust in the sense that a potential
      prior-data conflict, ie, a discrepancy between source and target data, is
      explicitly anticipated. The aim of this paper is to develop a solution for this
      particular application to showcase the ease of implementation by providing R
      code, and to demonstrate the robustness of the general approach in simulations.

PMID- 30302782
TI  - Defining predictive factors for reproductive output in captive common marmosets
      (Callithrix jacchus).
AB  - Common marmosets (Callithrix jacchus) demonstrate variations in reproductive
      output, not only in terms of total reproductive output during a lifetime but also
      in litter size per parturition. The present study explores factors, such as
      parents' litter size, parturition number, maternal body weight at conception and
      maternal age, which may account for this variation. A retrospective analysis of
      clinical records of a captive breeding colony was conducted over a 9-year period
      yielding reproductive summaries of 26 dams and 22 sires producing a total of 115
      litters. Dams born from litters of  <=2 (N = 20) more often produced litters of
      <=2, whereas dams born from litters of >2 (N = 6) more often produced litters of
      >2 (p < 0.05). The dams' maternal body weight at the time of conception had also
      a significant effect on subsequent litter size. In addition, the chance of
      triplets was higher after the second parturition. Maternal age, interbirth
      interval, and season of birth had no effect on litter size. Factors relating to
      the sire had a negligible effect on the size of the litter. Multivariate
      statistical modeling revealed that the dams' original litter size, maternal
      bodyweight at conception and parturition number are determining factors for the
      number of babies per litter. This study identified factors determining marmoset
      litter size, some of which (maternal litter size) are novel to this study and
      were not reported previously. Further exploration of the potential role of
      maternal litter size as a determinant of the litter sizes produced by marmoset
      breeders is warranted.

PMID- 30302783
TI  - Factors underlying suboptimal diagnostic performance in physicians under time
      pressure.
AB  - CONTEXT: Time pressure has been implicated in the suboptimal diagnostic
      performance of doctors and in increases in diagnostic errors. However, the
      reasons underlying these effects are not clear. The aim of this study was to
      investigate the influence of time pressure on physicians' diagnostic accuracy and
      to explore the mediating effects of perceived stress (emotional pathway) and
      number of plausible diagnostic hypotheses (cognitive pathway) on the proposed
      relationship. METHODS: We conducted a randomised controlled experiment. A total
      of 75 senior internal medicine residents completed eight written clinical cases
      under conditions with (n = 40) or without (n = 35) time pressure. They were then
      asked to: (i) rate the overall stress experienced, and (ii) write down any
      alternative hypotheses they had thought of when diagnosing the cases. In a post
      hoc analysis, a mediation path analysis was performed to test the causal
      relationships between time pressure, perceived stress and number of alternative
      diagnoses. RESULTS: Participants who were under time pressure spent less time
      diagnosing the cases (85.54 seconds versus 181.81 seconds; p< 0.001) and had a
      lower mean diagnostic accuracy score (0.44 versus 0.53; p = 0.01). In addition,
      they reported more stress (5.80 versus 4.69; p = 0.01) and generated fewer
      plausible tentative hypotheses (0.37 versus 0.51; p = 0.01). Two path
      coefficients were found to be statistically significant; the first path
      coefficient referred to the relationship between time pressure and perceived
      stress (standardised beta = 0.25, p = 0.029), and the second negative path
      coefficient referred to the relationship between time pressure and number of
      plausible alternative hypotheses (standardised beta = -0.32, p< 0.01).
      CONCLUSIONS: Time pressure adversely influences physicians' diagnostic accuracy
      by increasing their stress response and reducing the number of plausible
      hypotheses as mediators.

PMID- 30302785
TI  - Corrigendum.

PMID- 30302784
TI  - Power analysis for multivariable Cox regression models.
AB  - In power analysis for multivariable Cox regression models, variance of the
      estimated log-hazard ratio for the treatment effect is usually approximated by
      inverting the expected null information matrix. Because, in many typical power
      analysis settings, assumed true values of the hazard ratios are not necessarily
      close to unity, the accuracy of this approximation is not theoretically
      guaranteed. To address this problem, the null variance expression in power
      calculations can be replaced with one of the alternative expressions derived
      under the assumed true value of the hazard ratio for the treatment effect. This
      approach is explored analytically and by simulations in the present paper. We
      consider several alternative variance expressions and compare their performance
      to that of the traditional null variance expression. Theoretical analysis and
      simulations demonstrate that, whereas the null variance expression performs well
      in many nonnull settings, it can also be very inaccurate, substantially
      underestimating, or overestimating the true variance in a wide range of realistic
      scenarios, particularly those where the numbers of treated and control subjects
      are very different and the true hazard ratio is not close to one. The alternative
      variance expressions have much better theoretical properties, confirmed in
      simulations. The most accurate of these expressions has a relatively simple form.
      It is the sum of inverse expected event counts under treatment and under control
      scaled up by a variance inflation factor.

PMID- 30302786
TI  - A phase 1 healthy male volunteer single escalating dose study of the
      pharmacokinetics and pharmacodynamics of risdiplam (RG7916, RO7034067), a SMN2
      splicing modifier.
AB  - AIMS: Risdiplam (RG7916, RO7034067) is an orally administered, centrally and
      peripherally distributed, survival of motor neuron 2 (SMN2) mRNA splicing
      modifier for the treatment of spinal muscular atrophy (SMA). The objectives of
      this entry-into-human study were to assess the safety, tolerability,
      pharmacokinetics (PK) and pharmacodynamics of risdiplam, and the effect of the
      strong CYP3A inhibitor itraconazole on the PK of risdiplam in healthy male
      volunteers. METHODS: Part 1 had a randomized, double-blind, adaptive design with
      25 subjects receiving single ascending oral doses of risdiplam (ranging from 0.6
      18.0 mg, n = 18) or placebo (n = 7). A Bayesian framework was applied to estimate
      risdiplam's effect on SMN2 mRNA. The effect of multiple doses of itraconazole on
      the PK of risdiplam was also assessed using a two-period cross-over design (n =
      8). RESULTS: Risdiplam in the fasted or fed state was well tolerated. Risdiplam
      exhibited linear PK over the dose range with a multi-phasic decline with a mean
      terminal half-life of 40-69 h. Food had no relevant effect, and itraconazole had
      only a minor effect on plasma PK indicating a low fraction of risdiplam
      metabolized by CYP3A. The highest tested dose of 18.0 mg risdiplam led to
      approximately 41% (95% confidence interval 27-55%) of the estimated maximum
      increase in SMN2 mRNA. CONCLUSIONS: Risdiplam was well tolerated and proof of
      mechanism was demonstrated by the intended shift in SMN2 splicing towards full
      length SMN2 mRNA. Based on these data, Phase 2/3 studies of risdiplam in patients
      with SMA are now ongoing.

PMID- 30302787
TI  - What is the state of complexity science in medical education research?
AB  - CONTEXT: 'Complexity' is fast becoming a 'god term' in medical education, but
      little is known about how scholars in the field apply complexity science to the
      exploration of education phenomena. Complexity science presents both
      opportunities and challenges to those wishing to adopt its approaches in their
      research, and debates about its application in the field have emerged. However,
      these debates have tended towards a reductive characterisation of complexity
      versus simplicity. We argue that a more productive discussion centres on the
      multiplicity of complexity orientations, with their diverse disciplinary roots,
      concepts and terminologies. We discuss this multiplicity and use it to explore
      how medical education researchers have taken up complexity science in prominent
      journals in the field. METHODS: We synthesised the health sciences and medical
      education literature based on 46 papers published in the last 18 years (2000
      2017) to describe the patterns of use of complexity science in medical education
      and to consider the consequences of those patterns for our ability to advance
      scholarly conversations about 'complex' phenomena in our field. RESULTS: We
      identified four patterns in the use of complexity science in medical education
      research. Firstly, complexity science is described in a variety of ways.
      Secondly, multiple approaches to complexity are used in combination in single
      papers. Thirdly, the type of complexity science used tends to be left implicit.
      Fourthly, the complexity orientation used is much more commonly located using
      secondary source citation rather than primary source citation. CONCLUSIONS: The
      presence of these four patterns begs the question: Do medical education scholars
      understand that there are multiple legitimate orientations to complexity science,
      deriving from distinct disciplinary origins, drawing on different metaphors and
      serving distinct purposes? If we do not understand this, a cascade of potential
      consequences awaits. We may assume that complexity science is singular in that
      there is only one way to do it. This assumption may cause us to perceive our way
      as the 'right' way and to disregard other approaches as illegitimate. However,
      this perception of illegitimacy may limit our ability to enter into productive
      dialogue about our complexity science-inspired research.

PMID- 30302788
TI  - Gaze and the Eye Pupil Adjust to Imagined Size and Distance.
AB  - Pupillary responses and associated vergence eye movements were monitored during
      imagery of objects of differing sizes ("large" or "small") from varying distances
      ("near" or "far"). Objects' imagined size and distance affected oculomotor
      behavior. Objects visualized as "far" resulted in the larger pupil dilations and
      smaller visual angle, while small objects imagined "near" were associated with
      smaller pupils in contrast to relatively larger pupils when imagined as "far"
      away. Furthermore, near objects resulted in larger visual angle, and
      particularly, vergence adjustments were observed that were dependent on imagined
      size and distance of the small objects. The findings are consistent with the idea
      that imagery emulates perception, also at the embodied level of oculomotor
      behaviors.

PMID- 30302789
TI  - Investigation of structural stability and functionality of homodimeric gramicidin
      towards peptide-based drug: a molecular simulation approach.
AB  - Increasing death rates due to antibiotic resistance deteriorate the existing
      treatment measures. Antimicrobial peptides have turned into the emerging cure for
      multidrug resistance. However, the stability and functionality determine an
      antimicrobial peptide as a drug. Analyses of the homodimeric beta-helical
      peptide, gramicidin have suggested the significant role of gramicidin-A,
      gramicidin-B, and gramicidin-C as antimicrobial compounds, but the structural
      basis for understanding the stability and functionality is insufficient to
      resolve multidrug resistance. To identify the best template among gramicidin
      types as a therapeutic product, we combined a detailed comparative static
      analysis and dynamic analysis along with conformational free energy and secondary
      structure prediction. We observed that the high intramolecular interactions and
      the geometrical features favored gramicidin-A among other types of gramicidin.
      Our analyses further revealed that the secondary structure of gramicidin-A showed
      beta sheets with coils along the conformations without any disruption, thereby
      enhanced its membrane interactions in terms of binding free energy. In
      conclusion, gramicidin-A has definitely showed enhanced structural stability and
      functionality; this could be considered the best template for a potential
      therapeutic product.

PMID- 30302790
TI  - Upregulation of lincRNA-p21 in thoracic aortic aneurysms is involved in the
      regulation of proliferation and apoptosis of vascular smooth muscle cells by
      activating TGF-beta1 signaling pathway.
AB  - OBJECTIVE: Long intergenic noncoding RNA-p21 (lincRNA-p21) has been proved in the
      pathogenesis of aortic aneurysms, while its functionality in thoracic aortic
      aneurysms (TAA) and the mechanism of function remains unclear. Therefore our
      study aimed to investigate the role of lincRNA-p21 in TAA. METHODS: Aortic media
      specimens and blood samples were collected from both patients with TAA and
      healthy controls. Expression of lincRNA-p21 in those tissues was detected by
      reverse-transcription quantitative polymerase chain reaction (qRT-PCR).
      Diagnostic values of lincRNA-p21 in aortic media and blood for TAA were evaluated
      by receiver operating characteristic curve analysis. LincRNA-p21 overexpression
      human vascular smooth muscle cells (VSMCs) were prepared and the effects of
      lincRNA-p21 overexpression on cell proliferation and apoptosis were explored by
      cell counting kit-8 assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide assay, respectively. Expression of lincRNA-p21 and
      transforming growth factor beta1 (TGF-beta1) in VSMCs with different treatment
      was detected by qRT-PCR and Western blot analysis, respectively. RESULTS:
      Expression of lincRNA-p21 in aortic media tissues and blood was significantly
      upregulated in TAA patients than in healthy controls. Expression of lincRNA-p21
      in aortic media and blood can be used to effectively distinguish TAA patients
      form healthy controls. LincRNA-p21 overexpression inhibited proliferation and
      promoted apoptosis of VSMCs, while TGF-beta1 inhibitor reduced those effects.
      LincRNA-p21 overexpression upregulated TGF-beta1 expression, while TGF-beta1
      activator showed no significant effects on lincRNA-p21 expression in VSMC.
      CONCLUSION: LincRNA-p21 participates in TAA by regulating the proliferation and
      apoptosis of VSMCs through the activation of TGF-beta1 signaling pathway.

PMID- 30302791
TI  - Hypoxia-induced regulation of mTOR signaling by miR-7 targeting REDD1.
AB  - Oxygen is an important factor mediating cell growth and survival under
      physiological and pathological conditions. Therefore, cells have well-regulated
      response mechanisms in the face of changes in oxygen levels in their environment.
      A subset of microRNAs (miRNAs) termed the hypoxamir has been suggested to be a
      critical mediator of the cellular response to hypoxia. Regulated in development
      and DNA damage response 1 (REDD1) is a negative regulator of mammalian target of
      rapamycin (mTOR) signaling in the response to cellular stress, and is elevated in
      many cell types under hypoxia, with consequent inhibition of mTOR signaling.
      However, the underlying posttranscriptional regulatory mechanism by miRNAs that
      contribute to this hypoxia-induced reduction in REDD1 expression remain unknown.
      Therefore, the aim of the current study was to identify the miRNAs participating
      in the hypoxic cellular response by scanning the 3'-untranslated region (3'-UTR)
      of REDD1 for potential miRNA-binding sites using a computer algorithm,
      TargetScan. miR-7 emerged as a novel hypoxamir that regulates REDD1 expression
      and is involved in mTOR signaling. miR-7 could repress REDD1 expression
      posttranscriptionally by directly binding with the 3'-UTR. Upon hypoxia, miR-7
      expression was downregulated in HeLa cells to consequently derepress REDD1,
      resulting in inhibition of mTOR signaling. Moreover, overexpression of miR-7 was
      sufficient to reverse the hypoxia-induced inhibition of mTOR signaling.
      Therefore, our findings suggest miR-7 as a key regulator of hypoxia-mediated mTOR
      signaling through modulation of REDD1 expression. These findings contribute new
      insight into the miRNA-mediated molecular mechanism of the hypoxic response
      through mTOR signaling, highlighting potential targets for tumor suppression.

PMID- 30302792
TI  - MicroRNA-21 increases the expression level of occludin through regulating ROCK1
      in prevention of intestinal barrier dysfunction.
AB  - OBJECTIVE: The aim of this study is to investigate the role of molecular
      mechanism of microRNA (miR)-21 on tight junction (TJ)-proteins and its protective
      effects on the intestinal barrier. METHODS: TJ proteins and target genes
      expression were analyzed in miR-21 inhibition and overexpression NCM460 cell
      lines. To further verify the role of miR-21, the mmu-miR-21 intestinal epithelial
      conditional knockout (IKO) mice model was established. MiR-21 expression was
      detected in clinical specimens of acute stercoral obstruction patients. RESULTS:
      Rho-associated protein kinase 1 (ROCK1) were identified as target genes of miR
      21. There is a negative correlation between miR-21 expression level and TJ
      proteins levels. TJ protein and ROCK1 were significantly decreased in miR-21 IKO
      mice, which presented intestinal inflammation response and intestinal barrier
      dysfunction (both P < 0.05). Determination of clinical samples showed consistent
      results with NCM460 cell line and miR-21 IKO mice. CONCLUSIONS: MiR-21 could be a
      protective factor of intestinal barrier dysfunction, which promoting the
      expression of TJ protein by targeting ROCK1 in vivo and in vitro.

PMID- 30302793
TI  - Adalimumab treatment in Japanese patients with generalized pustular psoriasis:
      Results of an open-label phase 3 study.
AB  - A phase 3, multicenter, open-label, 52-week study investigated the efficacy and
      safety of adalimumab 80 mg at week 0 followed by adalimumab 40 mg every other
      week (option to escalate to 80 mg when necessary) in Japanese patients with
      generalized pustular psoriasis (GPP). Adults (aged 15-75 years) with GPP, total
      skin score (overall erythema area, erythema area with pustules, and edema area)
      of 3 or more, and erythema with pustules (skin score, >=1) based on the 2014
      Japanese Dermatological Association severity index of GPP were enrolled. The
      primary efficacy end-point was clinical response at week 16 (non-responder
      imputation), defined as achieving remission (total skin score, 0) or improvement
      from baseline (reduction of >=1 point from a baseline total skin score of 3 or
      >=2 points from a baseline total skin score of >=4). Of 10 enrolled patients
      (mean disease duration, 10.6 years), seven patients, including three with the
      dose escalated to 80 mg every other week before week 15, achieved clinical
      response at week 16, and five achieved clinical response at week 52. Mean change
      from baseline total GPP score was -4.6 at week 16 (n = 8) and -6.0 at week 52 (n
      = 5); change in total skin score was -3.1 (n = 8) and -4.2 (n = 5), respectively.
      Nine patients experienced one or more adverse events and three experienced
      serious adverse events. The most common adverse events were nasopharyngitis,
      pruritus and hypoalbuminemia. In conclusion, adalimumab was effective and well
      tolerated for up to 52 weeks in the treatment of Japanese patients with GPP.

PMID- 30302794
TI  - Macrophages express betaKlotho in skin lesions of psoriatic patients and the skin
      of imiquimod-treated mice.

PMID- 30302795
TI  - Roles for osteocalcin in proliferation and differentiation of spermatogonial
      cells cocultured with somatic cells.
AB  - Spermatogonial cells (SCs) are key cells for spermatogenesis. These cells are
      affected by paracrine signals originated from nearby somatic cells, among them
      Leydig cells have receptors for osteocalcin, a hormone known for exerting
      positive roles in the promotion of spermatogenesis. The aim of this study was to
      evaluate roles for osteocalcin on SCs proliferative and differentiation features
      after coculture with Leydig cells. SCs and Leydig cells were isolated from
      neonate NMRI offspring mice and adult NMRI mice, respectively. SCs population
      were then enriched in a differential attachment technique and assessed for
      morphological features and identity. Then, SCs were cocultured with Leydig cells
      and incubated with osteocalcin for 4 weeks. Evaluation of proliferation and
      differentiation-related factors were surveyed using immunocytochemistry (ICC),
      Western blot, and quantitative real-time polymerase chain reaction (PCR).
      Finally, the rate of testosterone release to the culture media was measured at
      the end of 4th week. Morphological and flow cytometry results showed that the SCs
      were the population of cells able to form colonies and to express ID4, alpha6-,
      and beta1-integrin markers, respectively. Leydig cells were also able to express
      Gprc6alpha as a specific marker for the cells. Incubation of SCs/Leydig coculture
      with osteocalcin has resulted in an increase in the rate of expressions for
      differentiation-related markers. Levels of testosterone in the culture media of
      SCs/Leydig was positively influenced by osteocalcin. It could be concluded that
      osteocalcin acts as a positive inducer of SCs in coculture with Leydig cells
      probably through stimulation of testosterone release from Leydig cells and
      associated signaling.

PMID- 30302796
TI  - Long noncoding RNA HOTAIRM1 inhibits cell progression by regulating miR-17-5p/
      PTEN axis in gastric cancer.
AB  - OBJECTIVES: This study was conducted to identify the significantly altered long
      noncoding RNAs (lncRNAs), messenger RNA (mRNA) and pathways in gastric cancer
      (GC). METHODS: We used microarray analysis to identify differentially expressed
      lncRNAs and mRNAs, whereas the obviously changed pathways were found by gene set
      enrichment analysis. The coexpression network of lncRNA and mRNA was constructed
      by Cytoscape, and their target relationships with miRNAs were predicted by
      miRcode and TargetScan. qRT-PCR and Western blot were performed to determine the
      expression levels of mRNAs and proteins in tissues and cell lines. Dual
      luciferase reporter assay was applied to achieve the determination of the
      specific target relationships. Cell viability, migration, and apoptosis were
      detected by MTT assay, wound healing assay and flow cytometry, respectively.
      Through the xenograft assay, the gastric tumor was implanted into nude mice to
      investigate the influence of HOTAIRM1 in vivo. RESULTS: HOTAIRM1 and phosphatase
      and tensin homolog (PTEN) were both downregulated in GC, whereas miR-17-5p was
      upregulated. Moreover, the PI3K/AKT pathway was found activated in GC. HOTAIRM1
      targeted miR-17-5p, whereas PTEN was the downstream target gene of miR-17-5p.
      HOTAIRM1 suppressed proliferation and migration of GC cell line and induced their
      apoptosis, whereas miR-17-5p played the opposite role on GC cell line. HOTAIRM1
      also postponed tumor growth in vivo and inhibited the PI3K/AKT pathway in GC.
      CONCLUSIONS: LncRNA HORAIRM1 suppressed the PI3K/AKT pathway in GC and inhibited
      the progression of GC by serving as a competing endogenous RNA of miR-17-5p,
      mediating the expression of PTEN.

PMID- 30302797
TI  - Immunofluorescent labeling of CD20 tumor marker with quantum dots for rapid and
      quantitative detection of diffuse large B-cell non-Hodgkin's lymphoma.
AB  - Fluorescent semiconductor quantum dots (QDs) are newfound nanocrystal probes
      which have been used in bioimaging filed in recent years. The purpose of this
      study is to evaluate the diagnostic value of specific QDs coupled to rituximab
      monoclonal antibody against CD20 tumor markers for patients with diffuse large B
      cell lymphoma (DLBCL). In current study rituximab-conjugated quantum dots (QDs
      rituximab) were prepared against CD20 tumor markers for detection of CD20
      positive cells (human Raji cell line) using flowcytometry. A total of 27 tumor
      tissue samples were collected from patients with DLBCL and 27 subjects with
      negative pathological tests as healthy ones, which stained by QD-rituximab. The
      detection signals were obtained from QDs using fluorescence microscopy. The
      flowcytometry results demonstrated a remarkable difference in fluorescent
      intensity and FL2-H + (CD20-positive cells percentage) between two groups. Both
      factors were significantly higher in Raji in comparison with K562 cell line (P <
      0.05). Lot of green fluorescence signals was observed due to the selectively
      binding of QD-rituximab to CD20 tumor markers which overexpressed in tumor
      tissues and a few signals observed on the defined healthy ones. Based on these
      observations the cut-off point was 46.8 dots and the sensitivity, specificity,
      positive predictive value, and negative predictive value were 100%, 89.5%, 91.3%,
      and 100%, respectively (LR+, 9.52; LR-, 0). The QD -rituximab could be beneficial
      as a bioimaging tool with high sensitivity to provide an accurate molecular
      imaging technique for identifying CD20 tumor markers for early diagnosis of the
      patients with DLBCL.

PMID- 30302798
TI  - Polymorphous light eruption with complication of solar urticaria revealed by
      phototesting.

PMID- 30302799
TI  - Identification of differentially expressed long noncoding RNAs in human knee
      osteoarthritis.
AB  - Long noncoding RNAs (lncRNAs) are considered a novel class of regulatory factors
      in many diseases, but their biological function and the signaling pathway
      involved in osteoarthritic (OA) remain unknown. To identify the lncRNAs
      specifically expressed in OA cartilage, the expression of lncRNAs in OA cartilage
      was measured using an illumina sequencing platform. Furthermore, differentially
      expressed transcripts of uncertain coding potential (TUCPs) and messenger RNAs
      (mRNAs) were identified. The colocated target genes and the possible role of
      lncRNAs as a competing endogenous RNA (ceRNA) were predicted. Based on 19 samples
      from osteoarthritis patients of knees, 580 significantly dysregulated lncRNAs as
      well as differently expressed TUCPs and mRNAs were identified. Four differently
      expressed lncRNAs (SNHG5, ZFAS1, GAS5, and DANCR) involved in OA cartilage were
      analyzed by protein-protein interactions network and ceRNA regulatory network.
      Part of our results were consistent with previous studies, and 96 novel
      differently expressed lncRNAs were identified in OA. These results could expand
      our knowledge of the OA mechanism.

PMID- 30302800
TI  - MiR-10a functions as a tumor suppressor in prostate cancer via targeting KDM4A.
AB  - Deregulation of microRNAs contributes to the abnormal cell growth which is
      frequently observed in cancer. In the current study, we detected the expression
      and regulatory relationship between miR-10a and Lysine-specific demethylase 4A
      (KDM4A) to reveal their function in prostate cancer (PCa) progression. We found
      that miR-10a levels were significantly decreased in PCa cell lines in comparison
      with the normal epithelial cell line RWPE-1. Downregulation of miR-10a levels was
      also observed in tumor tissues from PCa patients compared with the adjacent
      normal tissues. Enhanced expression of miR-10a inhibited cell proliferation and
      colony forming capability of PCa cells. In addition, quantitative real-time
      polymerase chain reaction and Western blot analysis showed a significant decrease
      of KDM4A in response to miR-10a elevation in PCa cells. Using dual luciferase
      assay, we confirmed that KDM4A was a target gene for miR-10a. Furthermore,
      Western blot analysis indicated that miR-10a overexpression inactivated YAP
      signaling and suppressed transcription of YAP target genes. Additionally, cell
      growth arrest and colony forming capacity inhibition induced by miR-10a
      overexpression could be reversed by YAP overexpression in PCa cells. More
      importantly, miR-10a mimics inhibited PC-3 tumor growth in nude mice accompanied
      with a remarkable reduction of KDM4A and YAP expression. In conclusion, our
      results uncovered a tumor suppressor role of miR-10a in PCa via negative
      regulation of KDM4A and its downstream Hippo-YAP pathway.

PMID- 30302801
TI  - MiR-143-3p suppresses cell proliferation, migration, and invasion by targeting
      Melanoma-Associated Antigen A9 in laryngeal squamous cell carcinoma.
AB  - Previously we found that melanoma-associated antigen-A9 (MAGE-A9) was a
      significantly upregulated biomarker in laryngeal squamous cell carcinoma (LSCC).
      A high expression of MAGE-A9 indicates an unfavorable survival outcome, and the
      MAGE-A9 expression level is an independent prognostic factor of LSCC. To explore
      the mechanism of MAGE-A9 upregulation, several predicted regulatory microRNAs
      were screened and validated in LSCC cells. In the current study, we found that
      miR-143-3p (MAGE-A9 related miRNAs) expression levels correlated negatively with
      the MAGE-A9 protein expression in LSCC tissues. Dual-luciferase reporter assays
      and Western blot analysis revealed MAGE-A9 to be a direct target of miR-143-3p.
      Furthermore, a series of in vitro gain- and loss-of-function assays revealed that
      miR-143-3p inhibited LSCC cell proliferation, migration, and invasion. Also, miR
      143-3p suppressed LSCC tumorigenesis in vivo. These effects were clinically
      relevant, as a lower expression of miR-143-3p occurred in severer clinical stages
      and represented poor overall survival in patients with LSCC. Taken together,
      these results suggest that downregulation of miR-143-3p contributes to tumor
      progression through upregulation of MAGE-A9. The expression level of these two
      key molecules maintained LSCC progression, thus, highlighting the potential of
      miR-143-3p as a therapeutic target for human LSCC.

PMID- 30302802
TI  - Unique dermoscopic feature of a long-standing pencil core granuloma on the head.

PMID- 30302803
TI  - A comparison of prenatal muscle transcriptome and proteome profiles between pigs
      with divergent growth phenotypes.
AB  - The growth of pigs is an important economic trait that involves multiple genes
      and coordinated regulatory mechanisms. The growth rate and potential of skeletal
      muscles are largely decided by embryonic myofiber development. Tibetan pig (TP)
      that is a mini-type breed has a divergent phenotype in growth rate and adult body
      weight with Wujin pig (WJ) and large White pig (LW). In the current study, the
      transcriptome (using RNA-seq) and proteome (using the isobaric tag for relative
      and absolute quantification [iTRAQ]) data from the prenatal muscle tissues were
      analyzed to identify the genes related to postnatal growth rate and growth
      potential in pigs. In the RNA-seq experiment, 19 626 genes were detected in the
      embryonic muscle tissues, and 3626 unique differentially expressed genes (DEGs)
      were identified in TP in comparison to that in LW and WJ. In the iTRAQ
      experiment, 2474 proteins were detected, and 735 unique differentially expressed
      proteins (DEPs) were identified in TP in comparison to that in LW and WJ.
      Combining the DEGs and DEPs, 209 genes were found to be differentially expressed,
      consistently at both the messenger RNA and protein levels, between TP and the
      other two breeds; these are mainly involved in 2-oxocarboxylic acid metabolism,
      citrate cycle, and biosynthesis of amino acids. Of these, 20 genes that were
      related to myoblast differentiation and muscle fiber formation might have
      important roles in determining the postnatal growth rate and potential body
      weight in pigs. Our results provide new candidate genes and insights into the
      molecular mechanisms involved muscle growth traits in pigs.

PMID- 30302804
TI  - Novel putative drugs and key initiating genes for neurodegenerative disease
      determined using network-based genetic integrative analysis.
AB  - Understanding the genetic causes of neurodegenerative disease (ND) can be useful
      for their prevention and treatment. Among the genetic variations responsible for
      ND, heritable germline variants have been discovered in genome-wide association
      studies (GWAS), and nonheritable somatic mutations have been discovered in
      sequencing projects. Distinguishing the important initiating genes in ND and
      comparing the importance of heritable and nonheritable genetic variants for
      treating ND are important challenges. In this study, we analysed GWAS results,
      somatic mutations and drug targets of ND from large databanks by performing
      directed network-based analysis considering a randomised network hypothesis
      testing procedure. A disease-associated biological network was created in the
      context of the functional interactome, and the nonrandom topological
      characteristics of directed-edge classes were interpreted. Hierarchical network
      analysis indicated that drug targets tend to lie upstream of somatic mutations
      and germline variants. Furthermore, using directed path length information and
      biological explanations, we provide information on the most important genes in
      these created node classes and their associated drugs. Finally, we identified
      nine germline variants overlapping with drug targets for ND, seven somatic
      mutations close to drug targets from the hierarchical network analysis and six
      crucial genes in controlling other genes from the network analysis. Based on
      these findings, some drugs have been proposed for treating ND via drug
      repurposing. Our results provide new insights into the therapeutic actionability
      of GWAS results and somatic mutations for ND. The interesting properties of each
      node class and the existing relationships between them can broaden our knowledge
      of ND.

PMID- 30302805
TI  - Identification of potential drugs targeting L,L-diaminopimelate aminotransferase
      of Chlamydia trachomatis: An integrative pharmacoinformatics approach.
AB  - Chlamydia trachomatis (C.t) is a gram-negative obligate intracellular bacteria,
      which is a major causative of infectious blindness and sexually transmitted
      diseases. A surge in multidrug resistance among chlamydial species has posed a
      challenge to adopt alternative drug targeting strategies. Recently, in C.t, L,L
      diaminopimelate aminotransferase (CtDAP-AT) is proven to be a potential drug
      target due its essential role in cell survival and host nonspecificity. Hence, in
      this study, a multilevel precision-based virtual screening of CtDAP-AT was
      performed to identify potential inhibitors, wherein, an integrative stringent
      scoring and filtration were performed by coupling, glide docking score, binding
      free energy, ADMET (absorption, distribution, metabolism, and excretion,
      toxicity) prediction, density functional theory (quantum mechanics), and
      molecular dynamics simulation (molecular mechanics). On cumulative analysis,
      NSC_5485 (1,3-bis((7-chloro-4-quinolinyl)amino)-2-propanol) was found to be the
      most potential lead, as it showed higher order significance in terms of binding
      affinity, bonded interactions, favorable ADMET, chemical reactivity, and greater
      stabilization during complex formation. This is the first report on
      prioritization of small molecules from National Cancer Institute (NCI) and
      Maybridge data sets (341 519 compounds) towards targeting CtDAP-AT. Thus, the
      proposed compound shall aid in effective combating of a broad spectrum of C.t
      infections as it surpassed all the levels of prioritization.

PMID- 30302806
TI  - LncRNA MNX1-AS1 promotes the progression of cervical cancer through activating
      MAPK pathway.
AB  - Long noncoding RNAs (lncRNAs) have been discovered as significant regulators in a
      wide range of human cancers. Among them, lncRNA MNX1-AS1 has been proved to be an
      oncogene in ovarian cancer and glioblastoma. However, the regulatory mechanism of
      MNX1-AS1 in cervical cancer remains to be understood. Therefore, this study
      planned to explore the role of MNX1-AS1 in cervical cancer. In the beginning, we
      found that the expression of MNX1-AS1 was obviously upregulated in cervical
      cancer tissues and cell lines. Kaplan-Meier survival analysis revealed that
      patients with higher MNX1-AS1 expression level suffered from shorter overall
      survival time than those with lower MNX1-AS1 level. Moreover, by loss-of-function
      and gain-of-function assay, the effect of MNX1-AS1 on cell proliferation and
      apoptosis was examined on cellular level. Results showed that the proliferation
      of Hela cells was significantly inhibited and apoptosis enhanced by the
      transfection of shMNX1-AS1, while overexpressing MNX1-AS1 in E6E7 cells presented
      the contrary results. As for mechanism investigation, it was demonstrated that
      overexpression of MNX1-AS1 significantly improved the expression of p-ERK1/2 and
      p-JNK. And the effects of MNX1-AS1 on cell proliferation and apoptosis would be
      diminished after inactivating the phosphorylation of either ERK or JNK. Taken
      together, it was identified that MNX1-AS1 promoted proliferation and inhibited
      apoptosis of cervical cancer cells through MAPK pathway.

PMID- 30302807
TI  - MiR-216b inhibits osteosarcoma cell proliferation, migration, and invasion by
      targeting Forkhead Box M1.
AB  - Osteosarcoma (OS) is considered the most common type of primary malignant bone
      tumor, which has a high rate of mortality in children and adolescents. However,
      the current treatment methods for OS are ineffective. Therefore, there is an
      urgent requirement to identify the critical targets. This study aimed to identify
      the roles and significance of microRNA-216b (miR-216b) in OS. To explore the
      cellular and molecular functions of miR-216b and Forkhead Box M1 (FoxM1) in OS,
      the expression of miR-216b and FoxM1 at the transcriptional level was measured
      using quantitative real-time PCR (qRT-PCR). Wound healing assay, 3-[4,5
      dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide assay (MTT) assay, flow
      cytometry, and transwell invasion assay were conducted to study the function of
      miR-216b and FoxM1 in OS cells. Dual luciferase reporter assay was performed to
      identify the relationships between miR-216b and FoxM1. qRT-PCR results revealed
      that miR-216b expression was significantly downregulated, and FoxM1 was observed
      to be significantly upregulated in human OS cell lines (MG-63) and tissues. MTT
      data showed that upregulation of miR-216b expression led to cell growth
      inhibition in MG-63 cells. The results of the invasion assay and wound healing
      assay illustrated that miR-216b upregulation or FoxM1 downregulation could
      inhibit the invasion and migration in MG-63 cells. In vivo, the tumor volume was
      significantly decreased by miR-194 mimic treatment compared with the control
      group. Furthermore, the results of the luciferase assay indicated that FoxM1 is a
      direct target of miR-216b. These findings may provide novel insights into the
      molecular mechanism of miR-216b and FoxM1 in the progression of OS, and suggested
      that miR-216b may serve as a potential tumor inhibitor of OS by targeting FoxM1.

PMID- 30302808
TI  - Embryonic poly(A)-binding protein is differently expressed and interacts with the
      messenger RNAs in the mouse oocytes and early embryos.
AB  - The embryonic poly(A)-binding protein (EPAB) functions in the translational
      regulation of the maternal messenger RNAs (mRNAs) required during oocyte
      maturation, fertilization, and early embryo development. Since there is no
      antibody specific to mammalian EPAB protein, all studies related to the Epab gene
      could be performed at the mRNA levels except for the investigations in the
      Xenopus. In this study, we have produced an EPAB-specific antibody. When we
      examined its expressional distribution in the mouse gonadal and somatic tissues,
      the EPAB protein was found to be expressed only in the mouse ovary and testis
      tissues, but it is undetectable level in the somatic tissues including stomach,
      liver, heart, small intestine, and kidney. Additionally, the spatial and temporal
      expression patterns of the EPAB and poly(A)-binding protein cytoplasmic 1
      (PABPC1) proteins were analyzed in the mouse germinal vesicle (GV) and metaphase
      II (MII) oocytes, one-cell, and two-cell embryos. While EPAB expression gradually
      decreased from GV oocytes to two-cell embryos, the PABPC1 protein level
      progressively increased from GV oocytes to one-cell embryos and remarkably
      declined in the two-cell embryos ( P < 0.05). We have also described herein that
      the EPAB protein interacted with Epab, Pabpc1, Ccnb1, Gdf9, and Bmp15 mRNAs
      dependent upon the developmental stages of the mouse oocytes and early embryos.
      As a result, we have first produced an EPAB-specific antibody and characterized
      its expression patterns and interacting mRNAs in the mouse oocytes and early
      embryos. The findings suggest that EPAB in cooperation with PABPC1 implicate in
      the translational control of maternal mRNAs during oogenesis and early embryo
      development.

PMID- 30302809
TI  - Ablation alleviates atrial fibrillation by regulating the signaling pathways of
      endothelial nitric oxide synthase/nitric oxide via miR-155-5p and miR-24-3p.
AB  - BACKGROUND: This study aimed to identify the microRNAs implicated in atrial
      fibrillation (AF) to investigate the molecular mechanisms underlying the role of
      microRNAs in ablation-based AF treatment. METHODS: Real-time polymerase chain
      reaction (PCR) and microRNA microarrays were utilized to measure the profiles of
      microRNA expression in AF to identify differentially expressed microRNAs. Enzyme
      linked immunosorbent assay, real-time PCR, Western blot analysis, and
      immunohistochemistry assays were also performed to investigate the regulatory
      relationships among various factors implicated in AF. Finally, bioinformatic
      tools and luciferase assays were used to confirm the roles of miR-155-5p, miR-24
      3p, endothelial nitric oxide synthase (eNOS), and nitric oxide (NO) in the
      pathogenesis of AF. RESULTS: We demonstrated that the levels of miR-155-5p and
      miR-24-3p were greatly reduced in postablation AF patients compared with those AF
      patients not treated by ablation. Furthermore, the NO level in the AF+ group was
      much lower than that of the AF- group. Finally, in a swine model of AF, evident
      upregulation of miR-155-5p and miR-24-3p was found in AF pigs, whereas the
      ablation treatment reduced the levels of miR-155-5p and miR-24-3p in AF pigs. On
      contrary, as targets of miR-155-5p and miR-24-3p, the levels of eNOS and NO
      increased when the expression of miR-155-5p and miR-24-3p decreased. CONCLUSION:
      MiR-155-5p and miR-24-3p are involved in the pathogenesis of AF via regulating
      the expression of eNOS and the production of NO. In addition, ablation treatment
      helps the recovery from AF by reducing the expression of miR-155-5p and miR-24
      3p.

PMID- 30302810
TI  - Photodynamic treatment with anionic nanoclays containing curcumin on human triple
      negative breast cancer cells: Cellular and biochemical studies.
AB  - Photodynamic treatment is a minimally invasive and clinically approved procedure
      for eliminating selected malignant cells with activation of a photosensitizer
      agent at a specific light. Little is known, however, about the phototoxic
      properties of curcumin, as a natural phenolic compound, against different types
      of cancers. It is generally accepted that cellular damage occurs during photo
      treatment. There is a limitation in using of curcumin as a drug due to its low
      solubility, but nanoparticles such as anionic nanoclays or layered double
      hydroxide (LDH) could overcome it. The aim of this study was to investigate
      cellular responses to curcumin-LDH nanoparticles after photodynamic treatment of
      MDA-MB-231 human breast cancer cells. For this purpose, the MDA-MB-231 human
      breast cancer cell line treated with curcumin-LDH nanoparticle and then
      irradiated (photodynamic treatment). After irradiation, lactate dehydrogenase
      assay, clonogenic cell survival, cell death mechanisms such as autophagy and
      apoptosis were determined. Cell cycle distribution after photodynamic therapy
      (PDT) and also intracellular reactive oxygen species (ROS) generation were
      measured. The result showed that curcumin-LDH-PDT has a cytotoxic and
      antiprolifrative effect on MDA-MB-231 human breast cancer cells. Curcumin-LDH-PDT
      induced autophagy, apoptosis, and G0/G1 cell cycle arrest in human breast cancer
      cell line. Intracellular ROS increased in MDA-MB-231 cancer cell line after
      treatment with curcumin-LDH along with irradiation. The results suggest that
      curcumin-LDH nanoparticle could be considered as a novel approach in the
      photodynamic treatment of breast cancer.

PMID- 30302811
TI  - Microporous cellulosic scaffold as a spheroid culture system modulates
      chemotherapeutic responses and stemness in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) treatments are evaluated by two-dimensional (2D)
      in vitro culture systems, despite their limited ability to predict drug efficacy.
      The three-dimensional (3D) microporous scaffold provides the possibility of
      generating more reliable preclinical models to increase the efficacy of cancer
      treatments. The physical properties of a microporous cellulosic scaffold were
      evaluated. The cellulosic scaffold was biocompatible and had a highly porous
      network with appropriate pore size, swelling rate, and stiffness of cancer cell
      cultures. Cellulosic scaffolds were compared with 2D polystyrene for the culture
      of HepG2 and Huh7 human HCC cells. Cellulosic scaffolds promoted tumor spheroid
      formation. Cells cultured on scaffolds were more resistant to chemotherapy drugs
      and showed upregulation of EpCAM and Oct4. The migration ability of HCC cells
      cultured on scaffolds was significantly greater than that of cells grown in 2D
      cultures as evidenced by the downregulation of E-cadherin. In addition, the
      proportion of CD44+/CD133+ HCC cancer stem cells (CSCs) was significantly greater
      in cells cultured on scaffolds than in those grown in 2D cultures. These findings
      suggest that cellulosic scaffolds effectively mimic the in vivo tumor behavior
      and may serve as a platform for the study of anticancer therapeutics and liver
      CSCs.

PMID- 30302812
TI  - Comparing the efficacy of pain managements after total hip arthroplasty: A
      network meta-analysis.
AB  - The aim of our current study is to compare efficiency of various interventions
      implemented for pain management after total hip arthroplasty (THA). PubMed and
      EMBASE were searched for randomized clinical trials (RCTs) reporting the pain
      scales for evaluate the efficacy of pain control after THA including at least one
      pair of direct control groups. Pain scale values and the associated 95% credible
      interval (CrI) were used to describe efficacy. Surface under the cumulative
      ranking curve (SUCRA) of each means of pain control was calculated to compare the
      relative ranking of different interventions. Thirty-five eligible literatures
      were involved in data analysis. The interventions for postoperative pain
      management we examined were psoas compartment block (PCB), posterior nerve block
      (PNB), fascia iliaca block (FIB), periarticular injection (PAI), femoral nerve
      block (FNB), lumbar plexus block (LPB), spinal anesthesia (SA), epidural
      analgesia (EPI), intrathecal morphine (IA), intravenous patient-controlled
      analgesia (IV-PCA), patient-controlled analgesia (PCA), onsteroidal anti
      inflammatory drug (NSAID), local infiltration analgaesia (LIA), and reverse LIA
      (rLIA). In 0 to 6 hours analysis, patients under SA were found to have
      significantly lower pain score and SA was ranked the best. In 6 to 12 hours
      analysis, SA was found to be significantly more effective than other
      interventions and its SUCRA was the highest. No intervention showed a significant
      effect on reducing pain score for 12 to 24 hours and 24 to 48 hours after THA. SA
      is the best intervention to reduce THA postoperative pain in the first 24 hours.
      LPB is a better choice to reduce pain 12 to 48 hours after THA.

PMID- 30302813
TI  - miR-17-5p promotes proliferation and epithelial-mesenchymal transition in human
      osteosarcoma cells by targeting SRC kinase signaling inhibitor 1.
AB  - MicroRNA-17-5p (miR-17-5p) and epithelial-mesenchymal transition (EMT) have been
      reported to participate in the development and progression of multiple cancers.
      However, the relationship between the miR-17-5p and EMT in osteosarcoma (OS) is
      still poorly understood. This study was to investigate the effects of the miR-17
      5p and its potential mechanism in regulating proliferation, apoptosis, and EMT of
      human OS. Quantitative real-time PCR was used to detect the miR-17-5p and SRC
      kinase signaling inhibitor 1 (SRCIN1) messenger RNA expression in OS specimens
      and cell lines. After transfection with miR-17-5p inhibitors, proliferation,
      apoptosis, migration, and invasion of OS cells were assessed by using the Cell
      Counting Kit-8, the annexin V-FITC apoptosis, wound-healing, and transwell
      assays. The SRCIN1 was validated as a target of the miR-17-5p through
      bioinformatics algorithms and luciferase reporter assay. Moreover, the expression
      of EMT markers, E-cadherin, N-cadherin, and Snail was identified by the Western
      blot analysis. MiR-17-5p was significantly upregulated in OS tumor samples and
      cell lines. It inhibited proliferation and EMT, and promoted apoptosis in OS. The
      SRCIN1 was identified as a direct target of the miR-17-5p. Silenced miR-17-5p
      could change the expression of EMT markers, such as upregulating the expression
      of E-cadherin, and downregulating the expression of N-cadherin and Snail through
      targeting the antioncogenic SRCIN1. These findings suggest that the miR-17-5p
      promotes cell proliferation, and EMT in human OS by directly targeting the
      SRCIN1, and reveal a branch of the miR-17-5p/SRCIN1/EMT signaling pathway
      involved in the progression of OS.

PMID- 30302814
TI  - Platelet-neutrophil interaction aggravates vascular inflammation and promotes the
      progression of atherosclerosis by activating the TLR4/NF-kappaB pathway.
AB  - Platelet-neutrophil interaction is well known for its role in inflammatory
      diseases; however, its biological role in atherosclerosis (AS) progression
      remains unclear. Human peripheral blood neutrophils were obtained to compare toll
      like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)
      1beta and myeloid-related proteins 8/14 (Mrp8/14) levels in 22 AS patients with
      those in 18 healthy controls using quantitative real-time polymerase chain
      reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Meanwhile,
      mouse marrow neutrophils subjected to different treatment were collected for the
      ELISA assay, cell apoptosis, and Western blot analysis. Normal diet or high-fat
      diet ApoE-/- mice with or without administration of Mrp8/14 antagonist paquinimod
      were used for plasma collection to measure total cholesterol, triglycerides, low
      density lipoprotein cholesterol and high-density lipoprotein cholesterol, TNF
      alpha, IL-1beta, Mrp8/14, TLR4, and nuclear factor (NF)-kappaB p65 levels. The
      results showed that Mrp8/14 and TLR4-mediated inflammatory pathway was activated
      in neutrophils of AS patients. In vitro experiments demonstrated that platelet
      neutrophil interaction promoted the Mrp8/14 release and inhibited neutrophil
      apoptosis via P-selectin. Furthermore, platelet-neutrophil interaction
      upregulated TLR4/myeloid differentiation factor 88/NF-kappaB pathway. Conversely,
      Mrp8/14/TLR4/NF-kappaB interference alleviated AS progression. In conclusion,
      Mrp8/14/TLR4/NF-kappaB activated by platelet-neutrophil interaction is an
      important inflammatory signaling pathway for AS pathogenesis.

PMID- 30302815
TI  - Evaluation of the attractant effect and lipid profile modulation of natural fixed
      oils on the medfly Ceratitis capitata (Wiedemann).
AB  - The Mediterranean fruit fly, Ceratitis capitata (Wiedemann, 1824; Diptera:
      Tephritidae), is a polyphagous pest in horticulture, mainly targeting Citrus
      fruits. Natural essential and fixed oils are currently under investigation for
      their broad-spectrum in pest control. To gain better knowledge about medfly
      behavior and biochemistry, we examined with behavioral and biochemical assays,
      the effects on C. capitata from six natural fixed oils obtained from vegetable
      (five) or animal (one) matrices using the eco-friendly supercritical CO 2
      extraction. Oils were obtained at 250/300 bar and 40 degrees C from the seeds of
      Laurus nobilis and Citrus paradisi, the fruits of Myristica fragrans and Pistacia
      terebinthus, wheat germ, and mullet roes (marine oil). Behavioral experiments
      were performed by means of two-choice tests to analyze the oil attractant effect
      compared with control (water or standard diet). The fatty acid composition of
      oils and the total lipid and fatty acid profile of medflies were characterized by
      chromatographic techniques. Behavioral bioassays showed that fixed oil obtained
      from M. fragrans (nutmeg butter) was more attractive than other oils. Medflies
      fed (24 hr) on marine oil showed significant changes in the total lipid and fatty
      acid profile induced by oil ingestion without toxic effects. However, 56%
      mortality was observed in insects fed on M. fragrans oil and no biochemical
      changes ascribable to oil ingestion were detected in the medflies that survived.
      Our results advance knowledge about the behavioral and biochemical response of
      medflies to fixed oils and will be potentially useful in developing new pest
      management strategies.

PMID- 30302816
TI  - Integrated network analysis and machine learning approach for the identification
      of key genes of triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) has attracted more attention compared with
      other breast cancer subtypes due to its aggressive nature, poor prognosis, and
      chemotherapy remains the mainstay of treatment with no other approved targeted
      therapy. Therefore, the study aimed to discover more promising therapeutic
      targets and investigating new insights of biological mechanism of TNBC. Six
      microarray data sets consisting of 463 non-TNBC and 405 TNBC samples were mined
      from Gene Expression Omnibus. The data sets were integrated by meta-analysis and
      identified 1075 differentially expressed genes. Protein-protein interaction
      network was constructed which consists of 486 nodes and 1932 edges, where 29 hub
      genes were obtained with high topological measures. Further, 16 features (hub
      genes), 12 upregulated (AURKB, CCNB2, CDC20, DDX18, EGFR, ENO1, MYC, NUP88, PLK1,
      PML, POLR2F, and SKP2) and four downregulated ( CCND1, GLI3, SKP1, and TGFB3)
      were selected through machine learning correlation based feature selection method
      on training data set. A naive Bayes based classifier built using the expression
      profiles of 16 features (hub genes) accurately and reliably classify TNBC from
      non-TNBC samples in the validation test data set with a receiver operating curve
      of 0.93 to 0.98. Subsequently, Gene Ontology analysis revealed that the hub genes
      were enriched in mitotic cell cycle processes and Kyoto Encyclopedia of Genes and
      Genomes pathway analysis showed that they were enriched in cell cycle pathways.
      Thus, the identified key hub genes and pathways highlighted in the study would
      enhance the understanding of molecular mechanism of TNBC which may serve as
      potential therapeutic target.

PMID- 30302818
TI  - Disparate roles of CXCR3A and CXCR3B in regulating progressive properties of
      colorectal cancer cells.
AB  - Human C-X-C Motif Chemokine Receptor 3A (CXCR3A) and CXCR3B are two splice
      variants of CXCR3 that is involved in a variety of progressive processes of
      cancer cells, including proliferation, migration, invasion, and tumorigenicity.
      However, the molecular mechanisms of CXCR3 in colorectal cancer (CRC) remain
      incomplete understood. In the present study, a significantly up-regulated CXCR3
      protein was firstly observed in CRC tissues and cell lines in comparison with the
      paired non-tumor tissues and normal intestinal epithelial cells, which was
      positively associated with CRC TNM stages. In contrast, CXCR3B was down-regulated
      in CRC tumor tissues compared with that in the corresponding paired paracancerous
      tissues, and negatively correlated with the TNM stages of cancer. Of interest,
      the overexpression of CXCR3A enhanced the progressive capacity of cell
      proliferation, migration, invasion in CRC LOVO and HCT116 cells in vitro, and the
      tumorigenicity in nude mice in vivo. Conversely, the overexpression of CXCR3B
      exhibited an opposite phenotype of CXCR3A, with an ability to inhibit the
      progressive properties in CRC cell lines in vitro and tumorigenesis in vivo. In
      addition, immunoblotting analysis further demonstrated that an increased
      expression of CXCR3A inhibited the expression of CXCR3B in CRC cells and NCM460
      normal colon epithelial cells; vice verse, an overexpression of CXCR3B suppressed
      the expression of CXCR3A in these cells. These data imply that an interaction
      between the CXCR3A and CXCR3B may play an important regulatory role in
      tumorigenicity of CRC, which warrants for further investigation.

PMID- 30302819
TI  - Long-term GPi-DBS improves motor features in myoclonus-dystonia and enhances
      social adjustment.
AB  - BACKGROUND: Good short-term results of pallidal deep brain stimulation have been
      reported in myoclonus-dystonia. Efficacy and safety in the long term remain to be
      established. In addition, the actual impact of DBS treatment on social inclusion
      is unknown. The objective of this study was to assess the long-term clinical
      outcome, quality of life, and social adjustment of GPi-DBS in patients with
      epsilon-sarcoglycan (DYT11)-positive myoclonus-dystonia. METHODS: Consecutive
      myoclonus-dystonia patients with epsilon-sarcoglycan mutations who underwent GPi
      DBS were evaluated at least 5 years postoperatively. Motor symptoms were assessed
      using the Burke-Fahn-Marsden Dystonia Rating Scale including the Disability
      Scale, a composite score combining the rest and action parts of the Unified
      Myoclonus Rating Scale and modified Abnormal Involuntary Movement Scale.
      Standardized video-protocols were assessed by a blinded and external movement
      disorder specialist. Social adjustment, cognition, and mood were evaluated.
      RESULTS: Nine patients (5 women) with long-term GPi-DBS (8.7 +/- 3.1 years) were
      included. There was significant improvement in the composite myoclonus score
      (94.1% +/- 4% improvement; P = 0.008). Dystonia severity was also markedly
      improved (71.4% +/- 28.33% improvement; P = 0.008) as well as motor disability
      (88.3% +/- 20% improvement; P = 0.008) and abnormal involuntary movement score
      (71.1% +/- 15.0% improvement; P = 0.008). No patients experienced postoperative
      speech or gait problems or any permanent adverse effects. Eight of the 9 patients
      had fully enhanced social adjustment and personal achievement, with little or no
      mood or behavioral disorders. CONCLUSIONS: GPi-DBS seems to be a safe and
      efficacious treatment for medically refractory E-sarcoglycan myoclonus-dystonia,
      with sustained motor benefit, good quality of life, and social adjustment in long
      term follow-up. (c) 2018 International Parkinson and Movement Disorder Society.

PMID- 30302820
TI  - Bias in parameter estimates due to omitting gene-environment interaction terms in
      case-control studies.
AB  - Genetic studies are continuing to generate volumes and variety of data that can
      be used to examine the genetic effects. Often the effect of a genetic variant
      varies by nongenetic measures, what is traditionally defined as gene-environment
      interaction (G*E). If the G*E term is neglected, estimates of the main effects
      can be substantially biased. We derive a general and convenient approximation to
      the magnitude of bias in the estimates due to omitting the G*E term. We show that
      the approximation is reasonably accurate in finite samples. We then apply the
      approximation in a study of Alzheimer's disease.

PMID- 30302821
TI  - Upregulated lncRNA small nucleolar RNA host gene 1 promotes 1-methyl-4
      phenylpyridinium ion-induced cytotoxicity and reactive oxygen species production
      through miR-15b-5p/GSK3beta axis in human dopaminergic SH-SY5Y cells.
AB  - Long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) has been
      demonstrated to be upregulated and play a crucial role in the pathology of
      Parkinson's disease (PD). However, the exact role of SNHG1 and its underlying
      mechanisms in PD remains elusive. In this study, we found that SNHG1 and glycogen
      synthase kinase 3 beta (GSK3beta) were upregulated, but miR-15b-5p was
      downregulated in 1-methyl-4-phenylpyridinium ion (MPP+ )-treated SH-SY5Y cells.
      The upregulation of SNHG1 enhanced MPP+ -induced cellular toxicity in SH-SY5Y
      cells, as shown by decreased cell viability, increased ROS production, and
      increased number of TdT-mediated dUTP Nick-End labeling-positive cells,
      accompanied with the upregulation of cleaved caspase 3 and elevation of
      cytochrome C release. Meanwhile, SNHG1 knockdown presented the converse effects.
      SNHG1 was demonstrated to interact with miR-15b-5p. Moreover, SNHG1 could
      attenuate the inhibitory effects of miR-15b-5p on MPP+ -induced cytotoxicity and
      production of ROS. Besides, GSK3beta was identified as a direct target of miR-15b
      5p. The inhibitory effects of SNHG1 knockdown or miR-15b-5p overexpression on
      MPP+ -induced cytotoxicity and reactive oxygen species (ROS) production were
      abrogated by upregulation of GSK3beta. Taken together, these results demonstrate
      that upregulated lncRNA SNHG1 promotes MPP+ -induced cytotoxicity and ROS
      production through the miR-15b-5p/GSK3beta axis in human dopaminergic SH-SY5Y
      cells, suggesting that SNHG1 may act as a potential therapeutic target for PD
      treatment in the future.

PMID- 30302822
TI  - Linearly distributed multiple lipomas: An unusual case report.

PMID- 30302823
TI  - Overlapping clustering of gene expression data using penalized weighted
      normalized cut.
AB  - Clustering has been widely conducted in the analysis of gene expression data. For
      complex diseases, it has played an important role in identifying unknown
      functions of genes, serving as the basis of other analysis, and others. A common
      limitation of most existing clustering approaches is to assume that genes are
      separated into disjoint clusters. As genes often have multiple functions and thus
      can belong to more than one functional cluster, the disjoint clustering results
      can be unsatisfactory. In addition, due to the small sample sizes of genetic
      profiling studies and other factors, there may not be sufficient evidence to
      confirm the specific functions of some genes and cluster them definitively into
      disjoint clusters. In this study, we develop an effective overlapping clustering
      approach, which takes account into the multiplicity of gene functions and lack of
      certainty in practical analysis. A penalized weighted normalized cut (PWNCut)
      criterion is proposed based on the NCut technique and an <mml:math
      xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>L</mml:mi>
      <mml:mn>2</mml:mn></mml:msub> </mml:math> norm constraint. It outperforms
      multiple competitors in simulation. The analysis of the cancer genome atlas
      (TCGA) data on breast cancer and cervical cancer leads to biologically sensible
      findings which differ from those using the alternatives. To facilitate
      implementation, we develop the function pwncut in the R package NCutYX.

PMID- 30302824
TI  - Comprehensive mapping of human body skin hydration: A pilot study.
AB  - BACKGROUND: Previous studies analyzed a series of representative anatomical
      regions in the human body; however, there is a wide structural and cellular
      variability in the constitution of the skin. Our objective was to perform a
      comprehensive assessment of human skin hydration throughout the largest possible
      area. MATERIALS AND METHODS: Hydration was registered by Corneometer(r) CM825
      probe in 23 anatomical regions of five healthy men. Each zone was analyzed by 2
      cm segments in the supine, prone, and lateral positions. A total of 7863
      measurements were registered. RESULTS: Differences in the degree of hydration
      among the prone, supine, and lateral regions were observed. The chest and back
      showed a pattern of increased hydration toward the neck area. Higher levels of
      hydration were evidenced in the proximal areas and in the regions near the elbow
      and knee. The regions of greater mechanical wear and with greater exposure to the
      sun exhibited a lower degree of hydration. CONCLUSION: The human skin exhibited
      hydration patterns influenced by anatomical function and the degree of sun
      exposure. Detailed information of the hydration patterns could serve as reference
      for the design of topical products, as an indicator of their effectiveness, and
      for the monitoring of skin pathologies.

PMID- 30302825
TI  - Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR-375/JAK2.
AB  - In this study, we sought to predict the effects of a certain circular RNA
      (circRNA), hsa_circ_101280 (also known as hsa_circ_0100929 and hsa_circ_SLAIN1),
      on hepatocellular carcinoma (HCC) cells and to determine the potential mechanism.
      After screening differentially expressed circRNAs in HCC tissues through Gene
      Expression Omnibus data analysis, hsa_circ_101280 was found to be highly
      expressed, and its high expression was verified in HCC cell lines with qRT-PCR
      along with the low expression of its downstream miRNA miR-375. Colony formation
      and flow cytometry assays showed that both hsa_circ_101280 silencing and miR-375
      overexpression restrained proliferation and promoted apoptosis in HCC cells. JAK2
      was identified as a downstream mRNA target of miR-375 by RNA pull-down and dual
      luciferase reporter gene assays, its expression in HCC cell lines were positively
      regulated by hsa_circ_101280 and negatively by miR-375 expression. Furthermore,
      the silencing of hsa_circ_101280 significantly inhibited the growth of HCC
      xenografts in nude mice, with the downregulated expression of JAK2. Overall, both
      the in vitro and in vivo studies revealed that hsa_circ_101280 largely
      facilitated the tumorigenesis of HCC, characterized by the promoted proliferation
      and suppressed apoptosis of HCC cells, by sponging miR-375 and upregulating JAK2.

PMID- 30302826
TI  - Advanced Materials for Next-Generation Spacecraft.
AB  - Spacecraft are expected to traverse enormous distances over long periods of time
      without an opportunity for maintenance, re-fueling, or repair, and, for
      interplanetary probes, no on-board crew to actively control the spacecraft
      configuration or flight path. Nevertheless, space technology has reached the
      stage when mining of space resources, space travel, and even colonization of
      other celestial bodies such as Mars and the Moon are being seriously considered.
      These ambitious aims call for spacecraft capable of self-controlled, self
      adapting, and self-healing behavior. It is a tough challenge to address using
      traditional materials and approaches for their assembly. True interplanetary
      advances may only be attained using novel self-assembled and self-healing
      materials, which would allow for realization of next-generation spacecraft, where
      the concepts of adaptation and healing are at the core of every level of
      spacecraft design. Herein, recent achievements are captured and future directions
      in materials-driven development of space technology outlined.

PMID- 30302827
TI  - Gastrointestinal: Successful endoscopic submucosal dissection assisted with
      endoloop for early appendiceal cancer that had everted into the cecal lumen.

PMID- 30302828
TI  - Sulfuration of an Fe-N-C Catalyst Containing Fex C/Fe Species to Enhance the
      Catalysis of Oxygen Reduction in Acidic Media and for Use in Flexible Zn-Air
      Batteries.
AB  - During the preparation of atomically dispersed Fe-N-C catalysts, it is difficult
      to avoid the formation of iron-carbide-containing iron clusters ("Fex C/Fe"),
      along with the desired carbon matrix containing dispersed FeNx sites. As a
      result, an uncertain amount of the oxygen reduction reaction (ORR) occurs, making
      it difficult to maximize the catalytic efficiency. Herein, sulfuration is used to
      boost the activity of Fex C/Fe, forming an improved system, "FeNC-S-Fex C/Fe",
      for catalysis involving oxygen. Various spectroscopic techniques are used to
      define the composition of the active sites, which include Fe-S bonds at the
      interface of the now-S-doped carbon matrix and the Fex C/Fe clusters. In addition
      to outstanding activity in basic media, FeNC-S-Fex C/Fe exhibits improved ORR
      activity and durability in acidic media; its half-wave potential of 0.821 V
      outperforms the commercial Pt/C catalyst (20%), and its activity does not decay
      even after 10 000 cycles. Interestingly, the catalytic activity for the oxygen
      evolution reaction (OER) simultaneously improves. Thus, FeNC-S-Fex C/Fe can be
      used as a high-performance bifunctional catalyst in Zn-air batteries. Theoretical
      calculations and control experiments show that the original FeNx active centers
      are enhanced by the Fex C/Fe clusters and the Fe-S and C-S-C bonds.

PMID- 30302829
TI  - Coding variation in GBA explains the majority of the SYT11-GBA Parkinson's
      disease GWAS locus.

PMID- 30302830
TI  - Innovation in dementia diagnosis: An evaluation of South Lakes virtual diagnostic
      memory clinic.

PMID- 30302831
TI  - Designed Nanoarchitectures by Electrostatic Spray Deposition for Energy Storage.
AB  - The development of advanced electrode materials for various energy-storage
      systems, especially the fabrication of designed structures and morphologies of
      electrode materials, has attracted intense interest in both the academic and
      industrial fields. Among the various synthesis methods, electrostatic spray
      deposition (ESD) is a simple but versatile approach, by which materials can be
      fabricated with various morphologies, such as granular, dense, and porous, in an
      easily controllable manner. Herein, motivated by the rapid advancements of the
      given technology, a comprehensive introduction of ESD is provided, with emphasis
      on the kinds of materials and the types of morphology that can be obtained, along
      with the important control parameters. The progress on electrode materials, which
      are applied in a great variety of energy-storage systems, such as Li-ion
      batteries, Na-ion batteries, supercapacitors, Li-S batteries, and Li-O2
      batteries, prepared by ESD is also summarized. How the specific morphologies
      designed by ESD improve the electrochemical performance for different types of
      electrode materials is also discussed. The aim is to promote the collaborative
      efforts among different communities to optimize and develop the ESD technique and
      to explore advanced electrode materials for energy storage.

PMID- 30302832
TI  - The Myths We Tell Ourselves About the Poor: From the English Poor Law to the
      Council of Economic Advisers.

PMID- 30302833
TI  - Investigation of treatment for azoospermia due to male hypogonadotropic
      hypogonadism in Japan.

PMID- 30302834
TI  - Interface Engineering for Garnet-Based Solid-State Lithium-Metal Batteries:
      Materials, Structures, and Characterization.
AB  - Lithium-metal batteries are considered one of the most promising energy-storage
      systems owing to their high energy density, but their practical applications have
      long been hindered by significant safety concerns and poor cycle stability. Solid
      state electrolytes (SSEs) are expected to improve not only the safety but also
      the energy density of Li-metal batteries. The key challenge for solid-state Li
      metal batteries lies in the low ionic conductivity of the SSEs and moreover the
      interface contact between the electrode and SSE. To achieve feasible solid-state
      Li-metal batteries, it is imperative that the ionic conductivity is improved,
      especially at the electrode-SSE interface. Herein, recent advances in interface
      engineering for solid-state Li-metal batteries are reported, mainly focusing on
      garnet-type SSEs. Various materials to modify the cathode-garnet and Li-garnet
      interfaces by intermediate layers, alloys, and polymer electrolytes are analyzed.
      Structural innovations for SSEs including composite electrolytes and multilayer
      SSE frameworks are reviewed, along with advanced characterization approaches to
      probe the interfaces, which will provide further insights for garnet-based solid
      state batteries. Future challenges and the great promise of garnet-based Li-metal
      batteries are discussed to close.

PMID- 30302835
TI  - C-Plasma of Hierarchical Graphene Survives SnS Bundles for Ultrastable and High
      Volumetric Na-Ion Storage.
AB  - Tin and its derivatives have provoked tremendous progress of high-capacity sodium
      ion anode materials. However, achieving high areal and volumetric capability with
      maintained long-term stability in a single electrode remains challenging. Here,
      an elegant and versatile strategy is developed to significantly extend the
      lifespan and rate capability of tin sulfide nanobelt electrodes while maintaining
      high areal and volumetric capacities. In this strategy, in situ bundles of robust
      hierarchical graphene (hG) are grown uniformly on tin sulfide nanobelt networks
      through a rapid (5 min) carbon-plasma method with sustainable oil as the carbon
      source and the partially reduced Sn as the catalyst. The nucleation of graphene,
      CN (with size N ranging from 1 to 24), on the Sn(111) surface is systematically
      explored using density functional theory calculations. It is demonstrated that
      this chemical-bonded hG strategy is powerful in enhancing overall electrochemical
      performance.

PMID- 30302836
TI  - A Surface Reconstruction Route to High Productivity and Selectivity in CO2
      Electroreduction toward C2+ Hydrocarbons.
AB  - Electrochemical carbon dioxide reduction (CO2 ) is a promising technology to use
      renewable electricity to convert CO2 into valuable carbon-based products. For
      commercial-scale applications, however, the productivity and selectivity toward
      multi-carbon products must be enhanced. A facile surface reconstruction approach
      that enables tuning of CO2 -reduction selectivity toward C2+ products on a copper
      chloride (CuCl)-derived catalyst is reported here. Using a novel wet-oxidation
      process, both the oxidation state and morphology of Cu surface are controlled,
      providing uniformity of the electrode morphology and abundant surface active
      sites. The Cu surface is partially oxidized to form an initial Cu (I) chloride
      layer which is subsequently converted to a Cu (I) oxide surface. High C2+
      selectivity on these catalysts are demonstrated in an H-cell configuration, in
      which 73% Faradaic efficiency (FE) for C2+ products is reached with 56% FE for
      ethylene (C2 H4 ) and overall current density of 17 mA cm-2 . Thereafter, the
      method into a flow-cell configuration is translated, which allows operation in a
      highly alkaline medium for complete suppression of CH4 production. A record C2+
      FE of ~84% and a half-cell power conversion efficiency of 50% at a partial
      current density of 336 mA cm-2 using the reconstructed Cu catalyst are reported.

PMID- 30302837
TI  - Programmable Multicomponent Self-Assembly Based on Aromatic Amino Acids.
AB  - Construction of integrated self-assembly with ordered structures from two or more
      organic building blocks is currently a challenge, since it suffers from intrinsic
      systematic complexity and diverse competitive pathways. Here, it is reported that
      aromatic amino acid building units can be incorporated into two- or three
      component coassembly driven primarily by hydrogen bonding interactions without
      the assistance of metal-ligand and macrocycle-based host-guest interactions. The
      key strategy is to employ a C3 -symmetric molecule with alternative hydrogen
      bonding donor/acceptor sites that are able to bind either carboxylic acid or
      pyridine appended building units. Aromatic amino acids, C3 -symmetric compound,
      and bipyridine unit constitute a unique ternary mutual binding system, where
      three coassembly pathways including two pairwise formations and one ternary
      combination are unveiled, giving rise to two- and three-component self-assemblies
      with ordered structures, respectively. The pathway complexity lies in the
      structural parameter of aromatic amino acids, which can be programmable by
      controlling substituents at the alpha-position of amino acids.

PMID- 30302838
TI  - Diabetes knowledge of primary health care and specialist nurses in a major urban
      area.
AB  - AIM AND OBJECTIVES: To examine trends since a previous 2006-2008 survey in
      diabetes knowledge held by primary health care nurses and their use of national
      diabetes guidelines, perceived ability to advise diabetes patients and
      preferences for further diabetes education. BACKGROUND: The obesity epidemic has
      led to a rapid increase in the prevalence of prediabetes and type 2 diabetes and
      to greater expectations for an expanded role for primary health care nurses in
      the prevention and community management of diabetes. DESIGN: Cross-sectional
      survey using a self-administered questionnaire and telephone interview and
      adheres to the STROBE guidelines. METHODS: All nurses who provide community-based
      care in a major urban area were identified, and stratified by group, prior to
      random selection to participate in the study. A total of 1,416 practice, district
      (home care) and specialist nurses were identified who provide community-based
      care. Of the 459 who were randomly selected, 336 (73%) participated in 2016 and
      were compared with a representative sample of 287 nurses surveyed in 2006-2008.
      RESULTS: Compared with nurses in 2006-2008, significantly more nurses in 2016
      used diabetes guidelines, knew that stroke was a diabetes-related complication,
      had a greater understanding of the pathology of diabetes and reported having
      sufficient knowledge to advise patients on laboratory results and improving
      outcomes through lifestyle changes. Despite these improvements, in 2016, only 24%
      of nurses could state that stroke was a complication of type 2 diabetes, only 37%
      felt sufficiently knowledgeable to advise patients on medications, and <20% could
      state that hypertension, smoking and the dyslipidaemia profile were important
      modifiable risk factors. CONCLUSION: There have been improvements in nurse's
      knowledge but gaps remain for cardiovascular outcomes and associated modifiable
      risk factors and medication management. RELEVANCE TO CLINICAL PRACTICE: Education
      programmes should focus on improving cardiovascular risk management in patients
      with type 2 diabetes.

PMID- 30302839
TI  - Compound heterozygous missense mutations p.Leu207Pro and p.Tyr544Cys in TGM1
      cause a severe form of lamellar ichthyosis.
AB  - TGM1 is the most common gene responsible for lamellar ichthyosis. Previous
      studies have suggested that patients with lamellar ichthyosis carrying two
      missense mutations in TGM1 show significantly less severe phenotypes than those
      with at least one truncating mutation in TGM1. Here, we report a patient with
      severe lamellar ichthyosis who was compound heterozygous for TGM1 missense
      mutations, including a novel one. A 22-year-old Japanese man presented with
      large, dark brown, plate-like scales on the extremities and small adherent scales
      on the face and trunk. His other clinical findings included ectropion, hair loss,
      hypohidrosis, hyperthermia in summer, palmoplantar keratoderma and constriction
      of the fingers. Dermoscopy revealed accentuated sulci cutis with numerous large
      keratotic plugs in the cristae cutis. Histologically, orthohyperkeratosis and
      mild acanthosis were noted. Electron microscopy showed reduced cornified envelope
      thickness and numerous lipid droplets in the stratum corneum. Mutation analysis
      revealed the patient to be compound heterozygous for missense mutations, c.620T>C
      (p.Leu207Pro) and c.1631A>G (p.Tyr544Cys), in TGM1. Furthermore, we showed that
      TGM1 enzymatic activity was largely absent in his epidermis. These findings led
      us to diagnose him as having lamellar ichthyosis. This study has two important
      notions. First, even two missense mutations in TGM1 can cause severe lamellar
      ichthyosis. Second, this is the first report of dermoscopic findings of lamellar
      ichthyosis, implicating the obstruction of sweat glands by keratotic plugs in the
      pathogenesis of hypohidrosis in the disease. In conclusion, this study provides
      further insights into genotype-phenotype correlations and pathogenesis in
      lamellar ichthyosis.

PMID- 30302840
TI  - Should second trimester hypoplastic nasal bone be a sole indication for
      diagnostic testing with chromosomal microarray?
AB  - Prior use of prenatal screening lowers the residual risk of trisomy 21 for women
      undergoing a midtrimester morphology scan. The International Society for
      Ultrasound in Obstetrics and Gynecology (ISUOG) issued a consensus statement
      stating that the 'genetic sonogram', which includes soft markers of trisomy 21,
      should not be performed in women with a low risk cfDNA screen due to poor
      positive predictive value.1 This article is protected by copyright. All rights
      reserved.

PMID- 30302841
TI  - Teething symptoms in children with congenital Zika syndrome: A 2-year follow-up.
AB  - BACKGROUND: The eruption of primary teeth represents a stage of many challenges
      for parents. AIM: To investigate the occurrence of signs and symptoms related to
      the eruption of the primary dentition in children with congenital Zika syndrome.
      DESIGN: Longitudinal study developed with 79 children followed up for a period of
      24 months. Data on sex, gestational age, low birthweight, microcephaly, signs and
      symptoms related to the dental eruption phase, and use and type of medication
      were collected. Data were presented by descriptive and inferential statistics
      (chi-square test). RESULTS: The majority (94.9%) exhibited simultaneously two or
      more signs and symptoms related to dental eruption. Increased salivation (91.1%),
      irritability (86.1%), and gingival itching (83.5%) were the most commonly
      reported signs and symptoms. Bivariate analysis showed association between
      elevation of body temperature and sex (P < 0.05). Almost two-thirds of mothers
      (63.3%) reported using medication to relieve symptoms presented by the child;
      however, the use of topical medication prevailed (57.1%). CONCLUSION: All
      children with congenital Zika syndrome presented manifestations related to the
      eruption of primary teeth, with increased salivation, irritability, and gingival
      pruritus. The use of ointments and gels was the option of mothers in the
      treatment of the oral discomfort presented by infants.

PMID- 30302843
TI  - Breastfeeding woman or lactating object? A critical philosophical discussion on
      the influence of Cartesian dualism on breastfeeding in the neonatal intensive
      care unit.
AB  - AIM: This discursive paper aims to bring to the foreground the ongoing influence
      of Cartesian dualism and other important contextual complexities on breastfeeding
      in the neonatal intensive care unit (NICU). BACKGROUND: Breastfeeding is widely
      supported as the optimal form of nutrition for the first 6 months of life and
      beyond. Amidst a myriad of contextual factors, current breastfeeding rates are
      below globally targeted goals. For premature and/or critically ill infants, the
      importance of receiving breast milk is often encouraged based on its
      immunological and nutritive benefits as opposed to the entirety of the
      breastfeeding interaction, underscoring the influence of dualism in the NICU.
      DESIGN: The impact of Cartesian dualism and other sociocultural underpinnings of
      breastfeeding focused within the NICU environment are illustrated through a
      critical, philosophical discussion. METHODS: Relevant historical context is
      provided followed by an overview of the realities of contemporary breastfeeding.
      These are presented as a frame of reference for the NICU breastfeeding
      experiences currently encountered by many mothers of preterm and critically ill
      neonates, further illustrated using a clinical exemplar as well as the author's
      own observations from neonatal nursing practice. RELEVANCE TO CLINICAL PRACTICE:
      Shifting away from a dualistic approach requires rethinking breastfeeding support
      interactions between NICU nurses and mothers. To address the disembodied and
      often mechanistic approach to care inherent in the dominant Western medical
      model, a relational approach to breastfeeding support in the NICU is suggested
      and discussed. CONCLUSION: Future research from a more critical lens is needed to
      examine the complex dynamics involved when nurses and mothers are negotiating
      decisions and processes related to infant feeding. In focusing on the relational
      dimensions of the breastfeeding experience, nurses can resist the dualistic
      influence and dominant discourses impacting infant feeding and motherhood in the
      21st century.

PMID- 30302842
TI  - Iron Gall Ink Revisited: In Situ Oxidation of Fe(II)-Tannin Complex for Fluidic
      Interface Engineering.
AB  - The ancient wisdom found in iron gall ink guides this work to a simple but
      advanced solution to the molecular engineering of fluidic interfaces. The Fe(II)
      tannin coordination complex, a precursor of the iron gall ink, transforms into
      interface-active Fe(III)-tannin species, by oxygen molecules, which form a self
      assembled layer at the fluidic interface spontaneously but still controllably.
      Kinetic studies show that the oxidation rate is directed by the counteranion of
      Fe(II) precursor salts, and FeCl2 is found to be more effective than FeSO4 -an
      ingredient of iron gall ink-in the interfacial-film fabrication. The optimized
      protocol leads to the formation of micrometer-thick, free-standing films at the
      air-water interface by continuously generating Fe(III)-tannic acid complexes in
      situ. The durable films formed are transferable, self-healable, pliable, and
      postfunctionalizable, and are hardened further by transfer to the basic buffer.
      This O2 -instructed film formation can be applied to other fluidic interfaces
      that have high O2 level, demonstrated by emulsion stabilization and concurrent
      capsule formation at the oil-water interface with no aid of surfactants. The
      system, inspired by the iron gall ink, provides new vistas on interface
      engineering and related materials science.

PMID- 30302844
TI  - Let's talk about sex: A feminist poststructural approach to addressing sexual
      health in the healthcare setting.
AB  - AIMS AND OBJECTIVES: To explore the use of feminist poststructuralism (FPS) as a
      way to critique, understand and improve sexual health care and policy in
      healthcare settings. BACKGROUND: Sexual health is an important aspect of health;
      however, in healthcare settings, it often goes unaddressed by both healthcare
      providers and patients due to stigma, taboo, fear of embarrassment or
      uncertainty. Lack of attention to sexual health has been stated as a legitimate
      concern for patients across the lifespan; there remain gaps in implementing
      sexual health care discussions into practice in healthcare settings. DESIGN: A
      critical analysis will be presented to explore sexual health care and attitudes
      in the healthcare setting from patient and nursing perspectives using FPS.
      METHODS: Feminist poststructuralism is used to examine the meaning of experience
      that is personally, socially and institutionally constructed through relations of
      power. FPS will also be applied to understand how sexual health discourses are
      negotiated in healthcare settings. SQUIRE guidelines were used in the preparation
      of this paper (See Appendix S1). RELEVANCE TO CLINICAL PRACTICE: The application
      of a feminist poststructural lens to sexual health care in healthcare settings
      may be used by healthcare professionals to understand, question and challenge how
      social and institutional beliefs, values and practices surrounding sexual health,
      inclusive of a patient's sexual pleasure or sexual activity, are experienced by
      healthcare professionals and patients. This theoretical and methodological
      approach could lead to identifying possibilities for change in healthcare
      settings that are inclusive and supportive of sexual health care.

PMID- 30302845
TI  - Ultrasound appearance of retroperitoneal pelvic Solitary Fibrous Tumor.
AB  - A 44-year-old woman was referred to our center after diagnosis of a pelvic mass
      on MRI. She had pain in sacral region for the last 8 months. Ultrasound
      examination showed a retrouterine solid mass of 72x75x86 mm in size, with a
      spherical shape and regular margins, inhomogeneous echotexture and no stripy
      shadows (Figure 1a). This article is protected by copyright. All rights reserved.

PMID- 30302846
TI  - Broken expectations of early motherhood: Mothers' experiences of early discharge
      after birth and readmission of their infants.
AB  - BACKGROUND AND AIM: Today, mothers are discharged early after birth, and national
      monitoring shows an increase in readmission of infants. Readmission of the infant
      might diminish the possibility of bonding and weaken maternal confidence in
      taking care of the infant. The aim was to explore how new mothers experience the
      time from birth to being discharged after readmission with their infants. DESIGN:
      A phenomenological and hermeneutic study. Data were collected through telephone
      interviews. The study followed the COREQ requirements and was conducted in the
      Region of Southern Denmark in a University Hospital setting. Convenience sampling
      was applied, and eight mothers were included from November 2015-February 2016.
      Seven were interviewed. RESULTS: The data analysis revealed the following six
      themes: "Early discharge," "Being at home," "Readmission-shock or relief,"
      "Problems with breastfeeding in early motherhood," "Empowering or disempowering
      guidance" and "Back home with broken expectations." These six themes were all
      covered by the overall theme: "Broken expectations of a tranquil beginning of
      early motherhood." CONCLUSIONS: Our study points out that mothers wish for a
      tranquil beginning with their infants at home. Some already experienced problems
      at home, while others first were confronted at the check-up at the outpatient
      clinic. Yet the common denominator was that the mothers experienced broken
      expectations regarding early motherhood when facing readmission. Readmission may
      influence the initial process either positively or negatively, depending on how
      the mothers experience their challenges and how the healthcare professionals
      support them. This highlights the importance of the way in which healthcare
      professionals support new mothers when they are readmitted. The study emphasises
      the importance of maternal feelings of security and confidence in their maternal
      role, as they are closely connected to the process of becoming a mother.

PMID- 30302847
TI  - Regulation of miR-125a expression by rs12976445 single-nucleotide polymorphism is
      associated with radiotherapy-induced pneumonitis in lung carcinoma patients.
AB  - BACKGROUND: The expression of miR-125 is regulated by an single-nucleotide
      polymorphism (SNP), rs12976445, which may be involved in the risk of pneumonitis
      among non-small-cell lung carcinoma patients undergoing the radiotherapy. We
      investigated this hypothesis via clinical data analysis and in vitro experiments.
      METHODS: An online microRNA (miRNA) database (www.mirdb.org) and luciferase
      reporter assays were used to confirm the role of transforming growth factor-beta1
      (TGFB1) as a target gene of miR-125a. Quantification by real-time PCR and Western
      blot analysis were used to measure the expression of miRNA-125a and TGFB1 among
      different groups (carrying CC, CT, and TT genotypes of rs12976445) or cells
      transfected with a scramble control, miR-125a mimics, TGFB1 siRNA, or miR-125a
      inhibitors. RESULTS: We evaluated 699 NSCLC patients and found that the patients
      carrying the TT or CT genotype of rs12976445 had a higher risk of radiotherapy
      induced pneumonitis. Computational analysis and luciferase assays validated that
      TGFB1 is a target gene of miR-125a. The expression level of miR-125a mRNA was
      significantly downregulated in the CT and TT groups, while the expression levels
      of TGFB1 and SMAD2 were significantly upregulated in the CC group. The expression
      of TGFB1 and SMAD2 was regulated by miR-125a in A549 cells. CONCLUSION: The
      rs12976445 SNP in miR-125a is associated with the risk of pneumonitis after in
      lung cancer patients undergoing the radiotherapy by regulating the expression of
      miR-125a and TGFB1.

PMID- 30302848
TI  - Attitudinal and behavioural responses to increasing tobacco control regulation
      among high smoking prevalence groups: A qualitative study.
AB  - INTRODUCTION AND AIMS: Despite substantial reductions in smoking prevalence in
      many countries, rates remain high among people who are experiencing disadvantage.
      This study aimed to explore attitudinal and behavioural responses to population
      wide tobacco control policies among Australian smokers experiencing disadvantage.
      DESIGN AND METHODS: Semi-structured qualitative interviews were conducted with 84
      smokers attending community service organisations in the mental health,
      homelessness, and alcohol and other drug sectors. Interviewees discussed various
      tobacco control policies (tobacco taxes, smoke-free areas, plain packaging and
      graphic health warnings). The interview transcriptions were coded and
      thematically analysed. RESULTS: Responses to tobacco taxes were mixed. Some
      interviewees reported smoking less as a result of price increases, while others
      reallocated funds from other budget areas. Many perceived smoke-free area
      policies as effective, although some described strategies they use to circumvent
      this policy, thereby diminishing its effectiveness. Plain packaging and graphic
      warnings were perceived as being least effective. DISCUSSION AND CONCLUSIONS:
      While tobacco control policies can elicit intended attitudinal and behavioural
      responses, additional efforts are needed to enhance their effectiveness among
      smokers experiencing disadvantage. Future efforts to reduce smoking rates should
      address responses that diminish policy effectiveness among groups exhibiting high
      smoking prevalence. This could be achieved through strategies that address the
      specific needs of these groups, such as providing additional cessation support,
      enforcing existing smoke-free policies in ways that minimise inequitable effects,
      and addressing self-exempting beliefs.

PMID- 30302849
TI  - Quality improvement programme of ultrasound based fetal anatomy screening using
      large scale clinical audit.
AB  - OBJECTIVE: Large scale audit and peer review of ultrasound images is
      advantageous, but is rarely performed consistently as it is time-consuming and
      expensive. Here we investigate the effect of large scale audit of routine fetal
      anatomy scans to assess if a full clinical audit cycle could improve clinical
      image acquisition standards. METHODS: A large scale, clinical, retrospective
      audit was conducted of ultrasound images from all routine anomaly scans
      undertaken in a UK hospital (from 18 weeks + 0 days to 22 weeks + 6 days) for one
      calendar year, to build a baseline understanding of the performance of
      sonographers. Targeted actions were undertaken in response to the findings with
      the aim of improving departmental performance. A second full year audit was then
      performed. An independent pool of sonographers used an online tool to assess all
      scans in two ways: scan completeness (i.e. were all images archived?) and image
      quality using objective scoring (i.e. were images of high quality?). Both were
      assessed at departmental level and at individual sonographer level. A 10% random
      sample of scans was used to assess inter-observer reproducibility. RESULTS:
      Images (n=103,501) from 6,257 anomaly scan examinations undertaken by 22
      sonographers were assessed in cycle 1 of the audit; in cycle 2, 153,557 images
      from 6,406 scans undertaken by 25 sonographers were evaluated. The analysis was
      performed on the 20 sonographers participating in both cycles. Departmental
      median scan completeness improved from 72% in the first year to 78% at the second
      assessment (p<0.001); median image quality score across all fetal views improved
      from 0.83 to 0.86 (p<0.001). The improvement was greatest for those sonographers
      who were performing poorest on the first audit: the 14% of poorest performing
      sonographers showed more than 30% improvement in scan completeness; and 11%
      showed more than 10% improvement in image quality. Inter-observer repeatability
      of scan completeness and image quality scores across different fetal views were
      similar to the published literature. CONCLUSION: Clinical audit and a set of
      targeted actions helped improve sonographer scan acquisition completeness and
      scan quality. Such adherence to recommended clinical acquisition standards may
      increase the likelihood of correct measurement and thereby fetal growth
      assessment; and should allow better detection of abnormalities. As such large
      scale audit is time consuming, further advantages would be achieved if this
      process could be automated. This article is protected by copyright. All rights
      reserved.

PMID- 30302850
TI  - Male partners' experiences of caregiving for women with cervical cancer-a
      qualitative study.
AB  - AIMS AND OBJECTIVES: This study aimed to develop knowledge on the experiences of
      male partners of women with cervical cancer during and after the illness. We
      explore men's experiences of becoming caregivers as well as how the illness
      trajectory affects or has affected the relationship. BACKGROUND: Receiving a
      cancer diagnosis has a significant impact on the lives of both the cancer patient
      and their family members. However, studies of male partners' experiences with
      cancer patients are scarce. Additionally, cervical cancer and its impact on male
      caregivers are less explored than how other cancer diagnoses impact male
      caregivers. The theoretical concept of caring masculinities is helpful to
      interpret men's experiences as caregivers and partners. DESIGN: The study employs
      a qualitative design with semi-structured interviews with six men/partners
      recruited through the gynaecological section at a hospital. COREQ reporting
      guidelines have been applied. FINDINGS: Based on our analyses, we find that men's
      experiences of being caregivers and partners of women treated for cervical cancer
      are multifaceted, comprising emotional and practical aspects. However, three main
      findings stand out as particularly significant for men in the context of cervical
      cancer: loneliness, an altered sexual relationship and shared feelings of
      vulnerability. CONCLUSIONS: The men describe an interdependence in the
      relationship with the women but also how the relationships have been seriously
      altered, particularly when it comes to sexuality. These findings resonate with
      hegemonic as well as caring masculinities. RELEVANCE TO PRACTICE: Complex issues
      of intimacy and sexuality should be a pivotal element in educating future
      healthcare professionals. We strongly suggest that issues such as dealing with
      masculinity and caregiving roles should be on the agenda and reflected upon in
      teaching and supervising in clinical practice. A broader approach to sexual
      health and relationships is needed in the patient-clinician relationships,
      including information about human papillomavirus.

PMID- 30302851
TI  - Harm reduction strategies related to dosing and their relation to harms among
      festival attendees who use multiple drugs.
AB  - INTRODUCTION AND AIMS: Polysubstance users are a high-risk population for
      negative health-related consequences. Although some studies have described harm
      reduction strategies adopted by polysubstance users, studies have not examined
      their effectiveness in minimising health-related consequences. We aimed to
      identify dosing-related harm reduction strategies in a sample of polysubstance
      using dance festival attendees, and explore the relationship between harm
      reduction strategies and self-reported adverse health consequences. DESIGN AND
      METHODS: Data were examined for 1226 past-year dance festival attendees who self
      identified as past-year multiple drug users. We conducted bivariable and
      multivariable analyses to explore relationships between six dosing-related harm
      reduction strategies and 13 self-reported adverse consequences. RESULTS: Self
      reported use of dosing-related harm reduction strategies was prevalent, mainly
      avoidance of mixing depressants (69.2%) and setting limits on quantity (62.2%).
      Frequent users of harm reduction strategies reported experiencing fewer adverse
      health consequences (P values < 0.05). Those who reportedly set limits on
      quantity were at decreased odds of experiencing a bad mood after drug use, sexual
      difficulties while under drug influence, injuries or fractures while under drug
      influence, and involvement in fights or being attacked while under drug influence
      (P values < 0.05). Moreover, those who report frequently avoid mixing depressants
      were at decreased odds of experiencing headache, loss of consciousness, drop in
      blood pressure, injuries of fractures, and fights or attacks (P values < 0.05).
      DISCUSSION AND CONCLUSIONS: Adoption of dosing-related harm reduction strategies
      appears to be associated with less drug-related harm among polysubstance-using
      festival attendees. Findings may inform organisations and policymakers in the
      designing of harm reduction interventions with this population.

PMID- 30302852
TI  - Gastrointestinal: Reversal of superior mesenteric artery syndrome following
      pregnancy.

PMID- 30302853
TI  - Long-term treatment with ivabradine in transgenic atrial fibrillation mice
      counteracts hyperpolarization-activated cyclic nucleotide gated channel
      overexpression.
AB  - INTRODUCTION: Recent studies have demonstrated that ivabradine (IVA), is a
      selective inhibitor of funny current (If) and exerts antiarrhythmic effects in
      the settings of various diseases such as heart failure and myocardial ischemia.
      However, little is known regarding the effects of long-term IVA treatment on If
      current and hyperpolarization-activated cyclic nucleotide gated (HCN) channel
      overexpression. METHODS AND RESULTS: We investigated both the If current and HCN
      channel expression in wild-type (WT) mice and transgenic (TG) atrial fibrillation
      (AF) mice (heart-specific overexpressing of (pro) renin receptor TG mice) and
      examined the effects of IVA on the If current and HCN channel expression, and
      whether those effects were sufficient to prevent an AF episode. Compared with WT
      mice, the If current density (at -170 mV: TG, -39.6 +/- 4.6 pA/pF; WT, -26.9 +/-
      3.0 pA/pF; P < 0.001) and activation kinetics (V1/2 : TG, -109.45 +/- 1.35 mV;
      WT, -128.20 +/- 1.65 mV), as well as HCN2 and HCN4 messenger RNA expression and
      HCN4 protein expression were significantly increased in the atrial myocytes of TG
      mice. After 4 months of IVA treatment (7 mg/kg per day orally) the effects of IVA
      on TG AF mice were accompanied by the inhibition of upregulation of HCN2 and HCN4
      protein expression in atrial tissue, and then resulted in a uniform If loss of
      function. Furthermore, we observed that ivabradine significantly decreased the
      incidence of AF in the TG mice (41.2% in TG mice, 16.7% in TG + IVA mice; P <
      0.01). CONCLUSION: IVA reduced the incidence of AF in mice, and the
      antiarrhythmic effects of IVA are not limited to heart rate reduction, as they
      partially counteract HCN overexpression and reverse electrophysiological cardiac
      remodeling by attenuating If gain-of-function.

PMID- 30302854
TI  - Assessment of microvascular dysfunction in acute limb ischemia-reperfusion
      injury.
AB  - BACKGROUND: Ischemia-reperfusion (I/R) injury involves damage to the microvessel
      structure (eg, increased permeability) and function (blunted vasomodulation).
      While microstructural damage can be detected with dynamic contrast-enhanced (DCE)
      MRI, there is no diagnostic to detect deficits in microvascular function.
      PURPOSE: To apply a novel MRI method for evaluating dynamic vasomodulation to
      assess microvascular dysfunction in skeletal muscle following I/R injury. STUDY
      TYPE: Prospective, longitudinal. ANIMAL MODEL: Twenty-three healthy male adult
      Sprague-Dawley rats. FIELD STRENGTH/SEQUENCE: Dynamic T1 fast field echo imaging
      at 3.0T with preinjection T1 mapping. ASSESSMENT: Injury in the left hindlimb was
      induced using a 3-hour I/R procedure. Longitudinal MRI scanning was performed up
      to 74 days, with animals completing assessment at different intervals for
      histological and laser Doppler perfusion validation. Pharmacokinetic parameters
      Ktrans and ve were determined following i.v. injection of gadovist (0.1 mmol/kg).
      Vasomodulatory response was probed on gadofosveset (0.3 mmol/kg) using
      hypercapnic gases delivered through a controlled gas-mixing circuit to induce
      vasoconstriction and vasodilation in ventilated rats. Heart rate and blood oxygen
      saturation were monitored. STATISTICAL TESTS: Two-way analysis of variance with
      Tukey-Kramer post-hoc analysis was used to determine significant changes in
      vasomodulatory response, Ktrans , and ve . RESULTS: This new MRI technique
      revealed impaired vasomodulation in the injured hindlimb. Vasoconstriction was
      maintained, but vasodilation was blunted up to 21 days postinjury (P < 0.05).
      However, DCE-MRI measured Ktrans and ve were significantly (P < 0.05) different
      from baseline only during acute inflammation (Day 3), with severe inflammation
      noted on histology. DATA CONCLUSION: While conventional DCE-MRI shows
      normalization after the acute phase, our new approach reveals sustained
      functional impairment in muscle microvasculature following I/R injury, with
      compromised response in vasomotor tone present for at least 21 days. LEVEL OF
      EVIDENCE: 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.

PMID- 30302855
TI  - Predictors of health related-quality of life among elderly with disabilities.
AB  - AIM: There have been no previous studies of health-related quality of life
      (HRQOL) among adults aged 65 years and older with disabilities in Serbia. The aim
      of study was to identify predictors of HRQOL in the context of sociodemographic
      characteristics, disability aetiology, comorbid diseases, indices of
      comorbidities, realization of social rights, and domestic violence. METHODS: The
      cross-sectional study involved 275 consecutive elderly outpatients with
      disabilities. They were recruited by general practitioners at Primary Health
      Centers in Belgrade, Serbia, from March to May 2015. Data were acquired through
      face-to-face interviews and general practitioners' charts, while the generic 36
      item Short Form Health Survey was used to assess HRQOL. In statistical analysis,
      Student's t-test, Z-test, Spearman's correlation test, and both univariate and
      multivariate linear regression were performed. RESULTS: Multivariate analysis
      revealed that a higher Functional Comorbidity Index (beta = -0.194, P < 0.01) and
      not asking for realization of right to assistance and care financial benefits
      (beta = -0.142, P < 0.05) were predictors of a lower scores Mental Composite
      Score (F = 9.262; P < 0.001). Not asking for realization of right to assistance
      and care financial benefits (beta = -0.187, P < 0.01), congestive heart failure
      (beta = -0.123, P < 0.05), and stroke (beta = -0.120, P < 0.05) were predictors
      of a lower Physical Composite Score (F = 7.169, P < 0.001). CONCLUSIONS: This
      study provides valuable data for better understanding the underlying factors
      associated with the HRQOL of elderly persons with disabilities, and currently,
      these are the only available data of their kind in Serbia. National authorities
      could identify predictors of HRQOL as a basic starting point for improving the
      social welfare and health-care systems. Better prevention and management of
      clinical factors, increased access to social services, and enhanced delivery of
      social services will improve the ageing process and HRQOL of this vulnerable
      population.

PMID- 30302856
TI  - Reinforce the antitumor activity of CD8+ T cells via glutamine restriction.
AB  - The antitumor activity of activated CD8+ T cells in the tumor microenvironment
      seems to be limited due to their being metabolically unfit. This metabolic
      unfitness is closely associated with T-cell exhaustion and impairment of memory
      formation, which are barriers to successful antitumor adoptive immunotherapy. We
      therefore assessed the role of glutamine metabolism in the antitumor activity of
      CD8+ T cells using a tumor-inoculated mouse model. The adoptive transfer of tumor
      specific CD8+ T cells cultured under glutamine-restricted (dGln) conditions or
      CD8+ T cells treated with specific inhibitors of glutamine metabolism efficiently
      eliminated tumors and led to better survival of tumor-inoculated mice than with
      cells cultured under control (Ctrl) conditions. The decreased expression of PD-1
      and increased Ki67 positivity among tumor-infiltrating CD8+ T cells cultured
      under dGln conditions suggested that the inhibition of glutamine metabolism
      prevents CD8+ T-cell exhaustion in vivo. Furthermore, the transferred CD8+ T
      cells cultured under dGln conditions expanded more efficiently against secondary
      OVA stimulation than did CD8+ T cells under Ctrl conditions. We found that the
      expression of a pro-survival factor and memory T cell-related transcription
      factors was significantly higher in CD8+ T cells cultured under dGln conditions
      than in those cultured under Ctrl conditions. Given these findings, our study
      uncovered an important role of glutamine metabolism in the antitumor activity of
      CD8+ T cells. The novel adoptive transfer of tumor-specific CD8+ T cells cultured
      in glutamine-restricted conditions may be a promising approach to improve the
      efficacy of cell-based adoptive immunotherapy.

PMID- 30302859
TI  - How do neonatal units within the Australian and New Zealand Neonatal Network
      manage ex-preterm infants with severe chronic lung disease still requiring major
      respiratory support at term?
AB  - AIM: The aim was to survey the Australian and New Zealand Neonatal Network
      (ANZNN) member units regarding current services and management guidelines for the
      ex-premature infant with severe chronic lung disease (CLD) still requiring
      significant respiratory support at term. METHODS: A 16-question survey was sent
      to clinical directors of all Level 3 units in Australia and New Zealand via the
      network. Reminder emails were sent, as required, to prompt a satisfactory
      response rate. RESULTS: Survey responses were received from 26 of the 29 (90%)
      ANZNN Level 3 units. At 37 weeks' corrected gestation, over 90% of the units
      provide ongoing respiratory support in the neonatal intensive care unit (NICU).
      However, by 50 weeks, ongoing care is provided in several settings, including
      NICU, high dependency unit (HDU)/paediatric intensive care unit or respiratory
      wards. The majority (76%) of units arrange transfer on an ad hoc basis, but six
      units (24%) have set criteria for transfer based on gestation, workload and
      respiratory requirement. Three units declared a maximum age in NICU (44, 46 or 48
      weeks). A variety of approaches were used to identify infants who were likely to
      require transfer, and 78% of units had a staff member assigned to assist
      transition. Three units stated that they had a home ventilation programme
      suitable for these infants. No unit supplied a guideline on tracheostomy or
      specific respiratory management post-term. CONCLUSION: Despite a significant
      number of babies requiring ongoing support for severe CLD, the location of the
      service appears very variable, and there is a lack of specific written
      guidelines.

PMID- 30302857
TI  - Primary breast diffuse large B-cell lymphoma in the rituximab era: Therapeutic
      strategies and patterns of failure.
AB  - Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of
      DLBCL with limited data on patterns of failure. This multicenter study aimed to
      define the optimum treatment strategy and patterns of failure for PB-DLBCL
      patients. We retrospectively reviewed data on 108 PB-DLBCL patients from 21
      Chinese medical centers. Only patients with localized disease (involvement of
      breast and localized lymph nodes) were included. After a median follow-up of 3.2
      years, 32% of patients developed progression or relapse. A continuous pattern of
      relapse was observed, characterized by frequent late relapses in the
      contralateral breast and central nervous system (CNS). Although rituximab
      significantly reduced the overall cumulative risk of progression or relapse (5
      year cumulative risk 57% vs 24%, P = .029), it had limited effect on the
      reduction of breast relapse (P = .46). Consolidative radiotherapy significantly
      decreased the risk of breast relapse, even in the subgroup of patients treated
      with rituximab (5-year cumulative risk 21.2% vs 0%, P = .012). A continuous risk
      of CNS progression or relapse up to 8.2 years from diagnosis was observed (10
      year cumulative risk 28.3%), with a median time to CNS relapse of 3.1 years.
      Neither rituximab nor prophylactic intrathecal chemotherapy significantly
      decreased the risk of CNS relapse. In summary, our study indicates that PB-DLBCL
      has a continuous pattern of relapse, especially with frequent late relapses in
      the CNS and contralateral breast. Rituximab and RT confer complementary benefit
      in the reduction of relapse. However, neither the addition of rituximab nor
      prophylactic intrathecal chemotherapy could effectively prevent CNS relapse for
      PB-DLBCL patients.

PMID- 30302858
TI  - A Dimeric 2,9-Diamino-1,10-phenanthroline Derivative Improves Alternative
      Splicing in Myotonic Dystrophy Type 1 Cell and Mouse Models.
AB  - Expanded r(CUG) repeats are the cause of the neurological disorder myotonic
      dystrophy type 1 (DM1). The pathological features of DM1 include the formation of
      ribonuclear foci containing expanded r(CUG) repeats, which sequester the MBNL1
      protein and lead to the misregulation of alternative pre-mRNA splicing. Small
      molecules that bind to the r(CUG) repeats and improve alternative splicing have
      therapeutic potential in the treatment of DM1. Herein, the synthesis of DDAP (a
      dimeric form of the CUG-binding molecule DAP reported previously), its binding
      properties to r(CUG) repeats, and its effect on the misregulation of splicing are
      reported. The surface plasmon resonance assay, circular dichroism spectra, and
      ESI-TOF mass spectrometry results confirmed the binding of DDAP to r(CUG)9
      repeats. Studies on a DM1 cell model and a DM1 mouse model revealed that DDAP was
      partially effective in the recovery of the pre-mRNA splicing defects. The
      mechanism underlying this recovery was studied in vitro through a competitive
      binding assay, and suggested that DDAP could interfere with the binding of MBNL1
      to r(CUG) repeats in a concentration-dependent manner.

PMID- 30302860
TI  - Harnessing the gatekeepers of glucocorticoids for chemoprevention of non-melanoma
      skin cancer.
AB  - Despite effective surgical methods for non-melanoma skin cancer (NMSC), patients
      suffer from tissue damage, scarring, or even disfigurement; thus, there is a need
      for chemopreventive approaches. Because of the complex interplay between
      glucocorticoids (GCs), inflammation, and cancer, we sought to determine the role
      of 11beta-hydroxysteroid dehydrogenase 1 and 2 (11betaHSD1 and 2) in regulating
      GCs during skin cancer development and progression. 11betaHSDs modulate the
      activation of GCs in a tissue-specific manner and have been reported to play a
      role in development and progression of other types of cancer, but their role has
      not yet been reported in NMSC. Here, we found a significant upregulation of
      11betaHSD2 protein in skin cancer cells when compared to normal skin cells,
      suggesting a role for this enzyme in the multifactorial process of skin cancer
      development. In addition, inhibition of 11betaHSD2 with siRNA resulted in
      significant reduction in colony formation in vitro. Finally, our in vivo study
      elucidated that inhibition of 11betaHSD2 with pharmacological inhibitor,
      Glycyrrhetinic acid (GA) could significantly diminish tumorigenesis in a well
      studied in vivo mouse model of NMSC. Overall, these studies highlight for the
      first time a potential novel role for 11betaHSD2 in NMSC development and may
      allow for new GC treatment approaches capable of avoiding deactivation by the
      enzyme. If 11betaHSD2 can be inhibited as we have done here, or circumvented
      using modified GCs, this may lead to more efficacious outcomes for NMSC patients
      by preventing deactivation of the GC and minimizing resistance.

PMID- 30302861
TI  - Validation of the Early Development Instrument for children with special health
      needs.
AB  - AIM: Population-level data on the development of children with special health
      needs attending primary school can assist special education, health and service
      delivery strategies. This study aims to determine whether results of the Early
      Development Instrument (EDI) can be interpreted and used with the same confidence
      for children with special health needs as for those who are typically developing.
      Psychometric properties of the EDI for kindergarteners with identified special
      health needs are examined. METHODS: Data for children with a special health need
      designation come from a database of all Canadian provincial implementations of
      the EDI between 2004 and 2014. Item and domain characteristics (distributions of
      scores and measures of internal consistency) of the EDI were examined. Construct
      validation was assessed by correlating EDI scores with gender and age. The fit of
      the original factor structure of the EDI was evaluated using confirmatory factor
      analysis. RESULTS: Data for 29 692 children (69.8% male) were analysed. The
      performance of items and domains was similar to that of typically developing
      children. As expected, boys scored lower on all EDI domains (Cohen's d: 0.03
      0.46) and a general, but non-significant, positive trend was observed between age
      and EDI scores. The factor structure of the EDI in this population yielded
      similar goodness-of-fit statistics as those reported in studies with typically
      developing children. CONCLUSION: Results of this investigation support the
      validity of the EDI in children with special health needs, paving the way for a
      more extensive use of EDI data for this vulnerable, yet often neglected,
      population.

PMID- 30302862
TI  - Effect of autonomic influences to induce triggered activity in muscular sleeves
      extending into the coronary sinus of the canine heart and its suppression by
      ranolazine.
AB  - INTRODUCTION: Extrasystoles arising from the muscular sleeves associated with the
      pulmonary veins (PV), superior vena cava (SVC), and coronary sinus (CS) are known
      to precipitate atrial fibrillation (AF). The late sodium channel current (INa )
      inhibitor ranolazine has been reported to exert antiarrhythmic effects in canine
      PV and SVC sleeves by suppressing late phase 3 early and delayed after
      depolarization (EAD and DAD)-induced triggered activity induced by
      parasympathetic and/or sympathetic stimulation. The current study was designed to
      extend our existing knowledge of the electrophysiological and pharmacologic
      properties of canine CS preparations and assess their response to inhibition of
      late INa following autonomic stimulation. METHODS: Transmembrane action
      potentials were recorded from canine superfused CS using standard microelectrode
      techniques. Acetylcholine (ACh, 1 uM), isoproterenol (Iso, 1 uM), high calcium
      ([Ca2+ ]o  = 5.4 mM), or a combination were used to induce EADs, DADs, and
      triggered activity. RESULTS: Action potentials (AP) recorded from the CS
      displayed short and long AP durations (APD), with and without phase 4
      depolarization (n = 19). Iso induced DAD-mediated triggered activity. The
      combination of sympathetic and parasympathetic agonists resulted in late phase 3
      EAD-induced triggered activity in all CS preparations. Ranolazine (5-10 uM)
      suppressed late phase 3 EAD- and DAD-induced triggered activity in 8 of 8
      preparations. Subthreshold stimulation induced a prominent hyperpolarization that
      could be suppressed by atropine. CONCLUSIONS: Our results suggest the important
      role of parasympathetic innervation in the activity of the CS. Autonomic
      influences promote DAD- and late phase-3-EAD-mediated triggered activity in
      canine CS, thus generating extrasystolic activity capable of initiating atrial
      arrhythmias. Ranolazine effectively suppresses these triggers.

PMID- 30302863
TI  - Arterial Spin Labeling MRI to Measure Cerebral Blood Flow in Untreated Ischemic
      Stroke.
AB  - BACKGROUND AND PURPOSE: This study aims to investigate the significance of
      regional hyperperfusion (RH) detected by arterial spin labeling (ASL) in a group
      of untreated stroke patients, within 24-36 hours after symptom onset. The
      relationship between RH volume and infarcted volume (DIV) as defined on diffusion
      weighted images (DWIs) was evaluated. METHODS: Of the 346 consecutive acute
      stroke patients who attended our center, we retrospectively reviewed MRI studies
      of 47 patients who were ineligible for standard treatment with intravenous tissue
      plasminogen activator. The MRI study included ASL and DWI. The ASL-derived
      cerebral blood flow (CBF) maps were coregistered on the DWI images. RH volume and
      DIV were calculated and compared. Patient NIHSS scores were also evaluated at
      admission, discharge, and after 1 and 6-month follow-up. RESULTS: Twenty-two
      patients showed RH with CBF twice than baseline. In all 22 patients, RH overlaps
      with DWI infarcted area. No significant difference (P = .94) between RH volume
      and DIV was found (7.2 +/- 9.6 and 9.0 +/- 11.9 cm3 ). The Pearson's correlation
      coefficient between RH and DIV was .93. On univariate analysis, a significant
      difference was found between patient's groups on NIHSS at any time points, after
      covariates adjustment NIHSS difference was significant only at admission.
      CONCLUSIONS: The study showed that ASL perfusion could be an integral part of the
      MRI examination in the assessment of 24-36 hours not-treated stroke patients as
      sustained RH group had improved outcomes. More importantly, ASL perfusion may
      provide evidence of beneficial effects of reperfusion induced by recanalization
      treatment.

PMID- 30302864
TI  - Diffusion tensor imaging of white matter in patients with prediabetes by trace
      based spatial statistics.
AB  - BACKGROUND: Prediabetes is an intermediate state in which blood glucose is higher
      than normal but does not meet the diagnostic criteria for diabetes. Diffusion
      tensor imaging (DTI) is an MRI method that can sensitively detect microscopic
      lesions in the white matter of the brain, but most previous DTI studies only
      focused on patients with diabetes, and little is known about prediabetes.
      PURPOSE: To investigate the changes in the microstructure of brain white matter
      in prediabetes patients using DTI and trace-based spatial statistics (TBSS).
      STUDY TYPE: Prospective. POPULATION: Sixty subjects (30 patients with prediabetes
      and 30 healthy volunteers) were enrolled. FIELD STRENGTH/SEQUENCE: 3.0T/DTI-MRI
      sequence with single-shot echo-planar imaging sequence (SE-EPI). ASSESSMENT: DTI
      data were collected and analyzed using the TBSS method in the FMRIB software
      library. STATISTICAL TESTS: DTI using a two-sample t-test. Pearson correlation
      analysis was performed on DTI values and neuropsychology scale results (mini
      mental state examination [MMSE], Montreal cognitive assessment [MoCA], self
      rating anxiety scale [SAS], and self-rating depression scale [SDS]) RESULTS:
      Compared with the control group, the fractional anisotropy (FA) values in the
      right part of the corpus callosum body (bCC) (P = 0.035), the right superior
      longitudinal fasciculus (SLF.R) (P = 0.047), and the left superior longitudinal
      fasciculus (SLF.L) in the prediabetic group were reduced (P = 0.040). DATA
      CONCLUSION: DTI as a noninvasive technique can assess early changes in the white
      matter microarchitecture of patients with prediabetes. LEVEL OF EVIDENCE: 2
      Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 30302865
TI  - English as a foreign language teacher training needs and perceived preparedness
      to include dyslexic learners: The case of Greece, Cyprus, and Poland.
AB  - This study examines the effect of demographic variables on the beliefs of
      teachers of English as a foreign language (EFL) about their preparedness to
      include dyslexic learners in mainstream classrooms in Greece, Cyprus, and Poland
      and identifies their professional development needs. Statistically significant
      multivariate analysis effects were obtained for country, training, teaching
      experience with dyslexic learners, and school type. Unlike overall teaching
      experience and completed level of education (degree), the type of teaching
      experience with dyslexic EFL learners (direct contact and personal involvement in
      teaching) seems to shape the perception of teacher preparedness to successfully
      include these learners. Other interesting tendencies were identified such as
      between-country differences concerning sources of prior professional knowledge on
      EFL and dyslexia as well as preferences for particular modes of training. The
      paper highlights the demand for professional training on EFL and dyslexia as this
      was confirmed across the three countries.

PMID- 30302866
TI  - Functional Brain Network Changes Following Use of an Allostatic, Closed-Loop,
      Acoustic Stimulation Neurotechnology for Military-Related Traumatic Stress.
AB  - BACKGROUND AND PURPOSE: Post-traumatic stress disorder is associated with
      connectivity changes in the default mode, central executive, and salience
      networks, and other brain regions. This study evaluated changes in network
      connectivity associated with usage of High-resolution, relational, resonance
      based electroencephalic mirroring (HIRREM(r) ; Brain State Technologies,
      Scottsdale, AZ), a closed-loop, allostatic, acoustic stimulation neurotechnology,
      for military-related traumatic stress. METHODS: Eighteen participants (17 males,
      mean age 41 years [SD = 7], 15 active duty) enrolled in an IRB approved pilot
      trial for symptoms of military-related traumatic stress. Participants received
      19.5 (1.1) HIRREM sessions over 12 days. Symptoms, physiological and functional
      measures, and whole brain resting MRI were collected before and after HIRREM. Six
      whole brain functional networks were evaluated using summary variables and
      community structure of predefined networks. Pre to postintervention change was
      analyzed using paired-sample statistical tests. RESULTS: Postintervention, there
      was an overall increase in connectivity of the default mode network (P = .0094).
      There were decreases of community structure in both the anterior portion of the
      default mode (medial prefrontal cortex, P = .0097) and in the sensorimotor (P =
      .005) network. There were no statistically significant changes at the whole brain
      level, or in the central executive, salience, or other networks analyzed.
      Participants demonstrated significant improvements in clinical symptoms, as well
      as autonomic cardiovascular regulation, which have been reported previously.
      CONCLUSIONS: Use of closed-loop, allostatic, acoustic stimulation neurotechnology
      (HIRREM) was associated with connectivity changes in the default mode and
      sensorimotor networks, in directions that may have explained the subjects'
      clinical improvements.

PMID- 30302868
TI  - Cardiac output measurements during high-risk caesarean section using electrical
      bioreactance or arterial wave form analysis: an assessment of agreement.
AB  - BACKGROUND: Maternal haemodynamics change significantly during Caesarean Section
      complicated by massive haemorrhage or severe hypertensive disease. Cardiac output
      (CO) monitoring aids early, goal-directed haemodynamic therapy. The aim of this
      study was to record haemodynamic changes observed during Caesarean section using
      invasive (LiDCOrapid) and non-invasive (NICOM(r) ) devices and to assess
      agreement between the two devices in measuring CO. METHODS: Simultaneous
      hemodynamic measurements were taken from the two devices using standardized
      techniques in women undergoing Caesarean section at high-risk of haemodynamic
      instability. Agreement was assessed using Bland-Altman plots and the
      Agreement/Tolerable Index (ATI). Agreement analyses were performed for repeated
      measures in subjects and using centiles. RESULTS: 307 paired data from 10
      patients were analysed. The mean bias (LiDCOrapid - NICOM(r) ) was 3.05 L.min-1
      (95% CI 1.89 to 4.21). Limits of Agreement ranged from -1.58 L.min-1 (95% CI 
      4.47 to -0.14) to 7.68 L.min-1 (95% CI 6.24 to 10.56). The resulting agreement
      interval was 9.26 L.min-1 which returned 2.3 as the ATI. CONCLUSION: The
      LiDCOrapid and NICOM(r) hemodynamic monitors exhibit large mean differences
      indicating that they should not be considered clinically interchangeable. There
      is an unacceptable level of agreement (ATI>2) conferring an extreme risk of
      clinical misclassification with massive hemorrhage. This article is protected by
      copyright. All rights reserved.

PMID- 30302867
TI  - FBXW7 modulates malignant potential and cisplatin-induced apoptosis in
      cholangiocarcinoma through NOTCH1 and MCL1.
AB  - The ubiquitin ligase F-box and WD repeat domain-containing 7 (FBXW7) is
      responsible for degrading diverse oncoproteins and is considered a tumor
      suppressor in many human cancers. Inhibiting FBXW7 enhances the malignant
      potential of several cancers. In this study, we aimed to investigate the role of
      FBXW7 in cholangiocarcinoma. We found that FBXW7 expression was associated with
      clinicopathological outcomes in cholangiocarcinoma patients. Both disease-free
      and overall survival were significantly worse in the low-FBXW7 group than in the
      high-FBXW7 group (P = .001 and P < .001, respectively). Multivariate analysis
      with the Cox proportional hazards model indicated that FBXW7 was the most
      important independent prognostic factor for disease-free (P = .006) and overall
      (P = .0004) survival. We also showed that the two FBXW7 substrates, NOTCH1 and
      myeloid cell leukemia sequence 1 (MCL1), regulate cholangiocarcinoma progression.
      Depletion of FBXW7 resulted in NOTCH1 accumulation and increased
      cholangiocarcinoma cell migration and self-renewal. Interestingly, when cells
      were stimulated with cis-diamminedichloridoplatinum(II) (cisplatin), FBXW7
      suppression induced MCL1 upregulation, which reduced the sensitivity of
      cholangiocarcinoma cells to apoptosis, indicating that FBXW7-mediated
      ubiquitylation is context-dependent. These results indicate that FBXW7 modulates
      the malignant potential of cholangiocarcinoma through independent regulation of
      NOTCH1 and MCL1.

PMID- 30302869
TI  - Involving young people in cyberbullying research: The implementation and
      evaluation of a rights-based approach.
AB  - BACKGROUND: Cyberbullying is an international Public Health concern. Efforts to
      understand and address it can be enhanced by involving young people. This paper
      describes a rights-based collaboration with young people in a qualitative
      exploration of cyberbullying. It describes the establishment, implementation and
      evaluation of a Young Person's Advisory Group as well as identifying the impact
      on the research process and the young people involved. METHODS: Sixteen
      postprimary school students met with researchers on five occasions in a youth
      centre. Sessions focused on building the young people's capacity to engage with
      the research, designing the qualitative study, interpreting study findings and
      evaluating the collaboration process. RESULTS: The Advisory Group highlighted a
      lack of understanding and appropriate action with regard to cyberbullying but
      believed that their involvement would ultimately help adults to understand their
      perspective. Evaluation findings indicate that members were supported to form as
      well as express their views on the design, conduct and interpretation of the
      research and that these views were acted upon by adult researchers. Their
      involvement helped to ensure that the research was relevant and reflective of the
      experiences, interests, values and norms of young people. CONCLUSION: Young
      people can contribute a unique perspective to the research process that is
      otherwise not accessible to adult researchers. The approach described in this
      study is a feasible and effective way of operationalizing young people's
      involvement in health research and could be adapted to explore other topics of
      relevance to young people.

PMID- 30302870
TI  - Substrate-Induced Self-Assembly of Cooperative Catalysts.
AB  - Dissipative self-assembly processes in nature rely on chemical fuels that
      activate proteins for assembly through the formation of a noncovalent complex.
      The catalytic activity of the assemblies causes fuel degradation, resulting in
      the formation of an assembly in a high-energy, out-of-equilibrium state. Herein,
      we apply this concept to a synthetic system and demonstrate that a substrate can
      induce the formation of vesicular assemblies, which act as cooperative catalysts
      for cleavage of the same substrate.

PMID- 30302871
TI  - Discovery and Elucidation of the Biosynthesis of Aspernidgulenes: Novel Polyenes
      from Aspergillus Nidulans by Using Serial Promoter Replacement.
AB  - Through serial promoter exchanges, we isolated several novel polyenes, the
      aspernidgulenes, from Aspergillus nidulans and uncovered their succinct
      biosynthetic pathway involving only four enzymes. An enoyl reductase (ER)-less
      highly reducing polyketide synthase (HR-PKS) putatively produces a 5,6-dihydro
      alpha-pyrone polyene, which undergoes bisepoxidation, epoxide ring opening,
      cyclization, and hydrolytic cleavage by three tailoring enzymes to generate
      aspernidgulene A1 and A2. Our findings demonstrate the prowess of fungal
      tailoring enzymes to transform a polyketide scaffold concisely and efficiently
      into complex structures. Moreover, comparison with citreoviridin and aurovertin
      biosynthesis suggests that methylation of the alpha-pyrone hydroxy group by
      methyltransferase (CtvB or AurB) is the branching point at which the biosynthesis
      of these two classes of compounds diverge. Therefore, scanning for the presence
      or absence of the gatekeeping alpha-pyrone methyltransferase gene in homologous
      clusters might be a potential way to classify the product bioinformatically as
      belonging to methylated alpha-pyrone polyenes or polyenes containing rings
      derived from the cyclization of the unmethylated 5,6-dihydro-alpha-pyrone, such
      as 2,3-dimethyl-gamma-lactone and oxabicyclo[2.2.1]heptane.

PMID- 30302872
TI  - Outcomes for patients with second primary malignancy after primary surgical
      treatment for early-stage squamous cell carcinoma of the oral cavity.
AB  - BACKGROUND: The purpose of our article was to describe a tertiary center's
      experience with patients with primarily surgically treated early-stage intraoral
      cancer with a second primary malignancy confirmed during follow-up. METHODS: A
      total of 183 patients were primarily surgically treated for oral cancer between
      2000 and 2004. Among these, 24 patients (13.1% (24/183)) met inclusion criteria.
      RESULTS: There were 22 men (91.7%) and 2 women (8.3%) with a median age of 59.5
      years. Patients with head and neck cancer with a second primary malignancy had
      significantly higher survival compared to nonhead and neck cancer with a second
      primary malignancy. Patients with head and neck cancer with second primary
      malignancy were diagnosed during the period of 14 to 45 months (median 29
      months), whereas nonhead and neck cancer with second primary malignancy occurred
      in a period of 7 to 46 months (median 19 months). CONCLUSION: This study
      highlights the importance of optimizing screening strategies for second primary
      malignancies. In order to improve the survival of patients with head and neck
      squamous cell carcinoma (HNSCC), effective programs of screening and/or
      chemoprevention of second primary malignancies are essential.

PMID- 30302873
TI  - Prognostic role of epiregulin/amphiregulin expression in recurrent/metastatic
      head and neck cancer treated with cetuximab.
AB  - BACKGROUND: Cetuximab combined with chemoradiotherapy is the standard therapy for
      recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). However,
      survival benefit is limited. The purpose of this study was to investigate the
      expression of epiregulin (EREG) and amphiregulin (AREG), as predictive prognostic
      markers for the efficacy of cetuximab combined with chemotherapy in R/M HNSCC.
      METHODS: We conducted a retrospective analysis of 37 patients diagnosed with R/M
      HNSCC. Tumor samples were analyzed for EREG and AREG mRNA gene expression, and
      clinical outcomes evaluated. RESULTS: Values of EREG and AREG were associated
      with significantly longer overall survival (OS) (P = .03 and P = .01,
      respectively), as well as progression-free survival (PFS) (P = .04 and P = .04,
      respectively). Multivariate analysis revealed that AREG expression was
      significantly associated with OS and PFS. CONCLUSIONS: Patients with
      recurrent/metastatic HNSCC with higher EREG and AREG gene expression appear to
      benefit more from cetuximab combined with chemoradiotherapy than those with lower
      expression.

PMID- 30302874
TI  - Rhodium-Catalyzed Enantioselective Defluorinative alpha-Arylation of Secondary
      Amides.
AB  - We exploited the reactivity of an electronically biased Michael acceptor to
      perform a defluorinative alpha-arylation reaction using a chiral diene(L*)
      rhodium catalyst. Through this methodology, we are able to obtain various
      secondary amides, containing a tertiary alpha-stereocenter and a beta,gamma
      unsaturated gem-difluoro olefin, with excellent enantioselectivities. This
      methodology addresses the limitations of the previously described alpha-arylation
      methods to construct stereo-labile tertiary alpha-stereocenters. Further
      investigation of the reaction via in situ 19 F NMR monitoring suggests that the
      formation of the product leads to the inhibition of the active rhodium catalyst.

PMID- 30302875
TI  - The Recovery Strengths Questionnaire for alcohol and drug use disorders.
AB  - INTRODUCTION AND AIMS: The Recovery Strengths Questionnaire (RSQ) is a 15-item
      self-report questionnaire that assesses an addicted individual's recovery
      strengths. This study aimed to validate the RSQ as a measure of recovery capital.
      DESIGN AND METHODS: As part of a larger study, 151 participants in addiction
      recovery groups from across the UK completed the RSQ. Participants also completed
      the Assessment of Recovery Capital questionnaire and provided some demographic
      information. RESULTS: The RSQ was found to be psychometrically sound, with high
      internal consistency and concurrent validity with the Assessment of Recovery
      Capital. RSQ scores were positively correlated with length of time in recovery
      and length of membership in recovery groups, and the scores could be used to
      discriminate between those in early and late recovery. Principal components
      analysis revealed a two-factor structure of recovery capital. These two factors
      were named 'within-group recovery strengths' and 'externally generated recovery
      strengths', and it was found that only the within-group factor scale (i.e.
      resources developed within recovery groups) predicted length of time in recovery
      and recovery groups. DISCUSSION AND CONCLUSIONS: These results highlight the
      important role that recovery groups can play in an individual's recovery, and
      they provide an alternative factor structure to the one-factor structure of the
      Assessment of Recovery Capital.

PMID- 30302876
TI  - Abstracts of the Association of Coloproctology of Great Britain and Ireland
      Annual Meeting, 9-11 July 2018, Birmingham, UK.

PMID- 30302877
TI  - Psychosocial benefits of insulin pump therapy in children with diabetes type 1
      and their families: The pumpkin multicenter randomized controlled trial.
AB  - OBJECTIVE: Continuous subcutaneous insulin infusion (CSII) is on the rise among
      pediatric patients with type 1 diabetes mellitus. Metabolic effects alone cannot
      explain this rising popularity. From the patient's perspective, the main benefits
      of CSII may be found in subjective psychosocial health outcomes (patient-reported
      outcomes [PRO]). SUBJECTS AND METHODS: In a multicenter open randomized
      controlled trial, children and adolescents aged 6 to16 years currently treated
      with multiple daily injections (MDI) were randomized 1:1, stratified by center,
      to either starting with CSII immediately after the baseline interview or to
      continuing MDI while waiting 6 months for transmission to CSII. The primary
      outcomes were patient-reported diabetes-specific health-related quality of life
      (DHRQOL) and diabetes burden of the main caregiver. Secondary outcomes were
      caregiver stress, fear of hypoglycemia, satisfaction with treatment, and HbA1c.
      RESULTS: Two-hundred and eleven patients were randomized between February 2011
      and October 2014, and 186 caregivers and 170 patients were analyzed using the
      intention-to-treat principle for primary outcomes. Children 8 to 11 years in the
      CSII group reported improved DHRQOL at follow-up compared to MDI (median
      difference [MD] 9.5, 95% confidence interval [CI] 3.6-16.7, P = 0.004). There
      were no treatment differences in the adolescent age-group 12 to 16 years (MD 2.7;
      95% CI -3.2-9.5; P = 0.353). The main caregivers of the CSII group reported a
      significant decline of overall diabetes burden at follow-up compared to the MDI
      group (MD 0; 95% CI -1-0; P = 0.029). Secondary PROs also were in favor of CSII.
      CONCLUSIONS: CSII has substantial psychosocial benefits. PROs demonstrate these
      benefits. Registered as NCT01338922 at clinicaltrials.gov.

PMID- 30302879
TI  - In this issue October 2018.

PMID- 30302878
TI  - Incidence of hypoglycemia in fasted young children referred for elective surgery.

PMID- 30302880
TI  - Reply to Galante, Dario, regarding their comment 'Tracheobronchial angles in
      children: Can it change during anesthesia?'

PMID- 30302881
TI  - Caudal and intravenous dexmedetomidine similarly prolong the duration of caudal
      analgesia in children: A randomized controlled trial.
AB  - BACKGROUND: Dexmedetomidine can prolong the duration of action of a local
      anesthetic agent, but the route of administration that is the most beneficial
      remains unclear. The purpose of this study was to compare the clinical
      effectiveness of caudal or intravenous dexmedetomidine administration on
      postoperative analgesia in children undergoing inguinal hernia repair given
      caudal levobupivacaine. METHODS: This was a prospective, randomized, double
      blinded, placebo-controlled trial. Ninety ASA I subjects, aged 2-5 year,
      undergoing unilateral inguinal hernia repair were enrolled. The children were
      randomized in a double-blind fashion to three groups. The L-Dcau group received 1
      mL/kg of caudal 0.25% levobupivacaine plus 1 MUg/kg dexmedetomidine and IV 20 mL
      saline. The L-Div group received 1 mL/kg of caudal 0.25% levobupivacaine and IV 1
      MUg/kg dexmedetomidine in 20 mL saline. The L group received 1 mL/kg of caudal
      0.25% levobupivacaine and IV 20 mL saline. The primary outcome was the duration
      of analgesia, which was defined as the time from the caudal block to a
      Postoperative Pain Scale (CHIPPS) score >=4. Secondary outcomes were the number
      of patients requiring rescue analgesia, pain intensity, the incidence of
      emergence agitation, intraoperative hemodynamic variations, residual motor block,
      and adverse effects. RESULTS: The median duration of analgesia in the L-Dcau
      group was 14.2 hour compared to 6 hour in the L group with a median difference of
      8.5 hour [95% CI (6.5, 10.5), P < 0.001]. The median duration of analgesia in the
      L-Div group was 12.4 hour compared to 6 hour in the L group with a median
      difference of 6.4 hour [95% CI (4, 8.5), P < 0.001]. Fewer patients in the L-Dcau
      and L-Div groups required rescue analgesia in the first 24 hour postoperatively
      compared to the L group, although there was no significant difference between the
      L-Dcau and L-Div groups for these outcomes. Both dexmedetomidine routes reduced
      the pain and the incidence of emergence agitation. No bradycardia, hypotension,
      or motor block was observed in any of the three groups. CONCLUSION: Caudal and IV
      dexmedetomidine similarly prolong the duration of analgesia produced by caudal
      levobupivacaine.

PMID- 30302882
TI  - In-hospital usability and feasibility evaluation of Panda, an app for the
      management of pain in children at home.
AB  - BACKGROUND: Postoperative pain in children is often poorly managed at home,
      leading to slower functional recovery, poor oral intake, sleep disturbances, and
      behavioral changes. Panda is a smartphone application (app) designed to support
      parents in assessing their child's pain and managing medications. AIMS: The aim
      of this study was to evaluate the Panda app's usability and feasibility in
      hospital prior to testing the app at home. METHODS: The study comprised two
      phases. Phase I evaluated Panda's usability with nurses, parents, and adolescents
      using simulated scenarios. Usability was measured by task completion rate, user
      error rates, and the Computer Systems Usability Questionnaire. Phase II evaluated
      Panda's feasibility by observing parents/guardians of pediatric patients using
      the app on the postsurgical ward. Feasibility was measured using response
      frequency and delay following app notifications from an audit trail of app
      function, and parental satisfaction from an interview. Feedback was used to guide
      iterative app improvements. RESULTS: In Phase I, 13 nurses, 12 parents, and 5
      adolescents evaluated the app. A total of 103 usability issues were identified,
      analyzed, and addressed. In Phase II, 29 parents responded to a total of 151 app
      notifications, with 84% responding within 1 hour in the final round of testing;
      93% of participants reported the app was easy to use, and rated the app with a
      median [interquartile range] Computer Systems Usability Questionnaire score of 2
      [1-4]. Significant barriers to use included lack of flexibility in the medication
      scheduling, low volume of alert sounds, and the extra time spent on medication
      safety checks. CONCLUSION: Panda's usability was improved and its feasibility
      demonstrated in the controlled hospital environment. The next step is to evaluate
      its feasibility for use at home.

PMID- 30302883
TI  - Autonomic cardiac regulation after general anesthesia in children.
AB  - BACKGROUND: General anesthesia dramatically decreases the activity of the
      autonomic nervous system. Most of the hypnotic agents used to induce anesthesia
      inhibit sympathetic cardiovascular regulation and baroreflex control in a dose
      dependent manner, lowering cardiac adaptability during the operation. The
      consequence of this effect in children during and after surgery has never been
      studied to date. AIM: The aim of this study was to follow the variations in
      autonomic cardiac indices in children younger than 8 years old after general
      anesthesia (6-24 hours) in programmed surgery. METHOD: A prospective descriptive
      monocentric study of 44 children under 8 years old who underwent scheduled
      surgery at our hospital center (Saint-Etienne University Hospital, France) was
      performed between June 1, 2016 and November 1, 2016. Heart rate variability was
      monitored for 24 hours using Holter-ECG devices and the resulting data were
      interpreted using linear and nonlinear analyses. RESULTS: Compared to baseline
      thresholds before surgery, all heart rate variability indices decreased
      dramatically during general anesthesia. After awakening, a slight reduction in
      sympathetic activity persisted 6 hours after surgery, but all measurements of
      sympathetic and parasympathetic activity had returned to baseline thresholds 12
      hours after the operation. Twenty-four hours after surgery, some parameters had
      increased above the corresponding baseline levels. CONCLUSION: Autonomic nervous
      function normalizes rapidly (within 12 hours) in prepubertal children. This study
      indicates that general anesthesia does not seem to increase the long-term risk of
      autonomic dysfunction in these patients.

PMID- 30302884
TI  - Ultrasound-guided serratus anterior plane block for effective pain control after
      resection of large chest wall vascular malformation in a child with Phosphatase
      and Tensin (PTEN) hamartoma tumor syndrome.

PMID- 30302885
TI  - A simple care bundle to reduce unplanned admission rate for day case pediatric
      circumcision.
AB  - BACKGROUND: An electronic review of unplanned day case admission rates in our
      hospital demonstrated an average annual rate for pediatric circumcision of 2%-3%
      in recent years with high levels of perioperative strong opiate use. This lay
      above target unplanned admission rates (<2%) set out by the Royal College of
      Anaesthetists for day case surgery. A targeted quality improvement initiative was
      undertaken to improve patient flow through the pediatric day case surgery unit
      for elective circumcision. Among the reasons for unplanned admission, factors
      modifiable by the anesthetist (pain, postoperative nausea and vomiting,
      somnolence) are significant contributors. METHODS: A prospective audit was
      undertaken over a 3-month period. Our practice was compared with evidence-based
      analgesic and antiemetic interventions in accordance the Association of
      Paediatric Anaesthetists of Great Britain and Ireland. Perioperative strong
      opiate administration rates occurred in 44% of cases. Four strategic
      interventions were selected based on quality of evidence, ease of implementation,
      and low cost: selection of higher concentration local anesthetic use for penile
      blocks, intravenous dexamethasone, and preoperative paracetamol combined with
      maximum dose nonsteroidal anti-inflammatory. RESULTS: The audit was duplicated a
      year later demonstrating a significant increase in application of these
      interventions with a parallel fall in strong opiate use from 44% to 9% and an
      unprecedented zero unplanned admission rate in our unit for 10 months in a row
      after implementation. CONCLUSION: Regular scrutiny of patient electronic data
      helps identify high impact areas for audit and intervention. Unplanned admission
      in pediatric day case surgery is an area amenable to such targeted intervention.

PMID- 30302886
TI  - Correcting for repeated outcome measures.

PMID- 30302887
TI  - A cluster of high psychological and somatic symptoms in children with idiopathic
      scoliosis predicts persistent pain and analgesic use 1 year after spine fusion.
AB  - BACKGROUND: Persistent postoperative pain is a significant problem for many
      children, particularly for those undergoing major surgery such as posterior spine
      fusion. More than two-thirds report persistent pain after spine fusion, yet
      factors that may contribute to poorer outcomes remain poorly understood. AIMS:
      This prospective, longitudinal study examined how psychologic and somatic
      symptoms cluster together in children aged 10-17 years with idiopathic scoliosis,
      and tested the hypothesis that a higher psychological and somatic symptom cluster
      would predict worse pain outcomes 1 year after fusion. METHODS: Otherwise healthy
      children with idiopathic scoliosis completed preoperative surveys measuring
      recent pain intensity, pain location(s), somatic symptom severity, painDETECT
      (neuropathic-type pain symptoms), pain interference, fatigue, depression,
      anxiety, and pain catastrophizing. Pain outcome data were collected during
      hospitalization, and at 1 year after surgery. RESULTS: Ninety-five children
      completed baseline surveys and a cluster analysis differentiated 28 (30%) with a
      high symptom profile that included; higher depression, fatigue, pain
      interference, catastrophizing, and painDETECT scores. High symptom cluster
      membership independently predicted higher pain interference at 1 year (beta 9.92
      [95% CI 6.63, 13.2], P < 0.001). Furthermore, children in this high symptom
      cluster reported significantly higher pain intensity and painDETECT scores, and
      had a 50% higher probability of continued analgesic use at 1 year compared to
      those in the Low Symptom Cluster (95% CI 21.3-78.5, P = 0.001). CONCLUSION:
      Findings from this exploratory study suggest a need to comprehensively assess
      children with scoliosis for preoperative signs and symptoms that may indicate an
      underlying vulnerability for persistent pain. This, in turn may help guide a
      comprehensive perioperative treatment strategy to mitigate the potential for long
      term pain trajectories.

PMID- 30302888
TI  - Can population cohort studies assess the long-term impact of anesthesia in
      children?

PMID- 30302889
TI  - A Stable Bifunctional Catalyst for Rechargeable Zinc-Air Batteries: Iron-Cobalt
      Nanoparticles Embedded in a Nitrogen-Doped 3D Carbon Matrix.
AB  - Low-cost, efficient bifunctional electrocatalysts are needed to mediate the
      oxygen reduction and oxygen evolution reactions (ORR/OER) in Zn-air batteries.
      Such catalysts should offer binary active sites and an ability to transfer oxygen
      based species and electrons. A 3D catalyst, composed of nanoparticles of CoFe
      alloy embedded in N-doped carbon nanotubes tangled with reduced graphene oxide,
      was developed, which presents appreciable ORR/OER activity when applied in a Zn
      air battery. A high open-circuit voltage of 1.43 V, a stable discharge voltage of
      1.22 V, a high energy efficiency of 60.1 %, and excellent stability after 1 600
      cycles at 10 mA cm-2 are demonstrated. An all-solid-state battery had an
      outstanding lifetime and high cell efficiency even upon bending. In situ X-ray
      absorption spectroscopy revealed that OOH* and O* intermediates induce variations
      in the Fe-Fe and Co-Co bond lengths, respectively, suggesting that Fe and Co
      species are crucial to the ORR/OER processes.

PMID- 30302891
TI  - Re: Developing a set of consensus indicators to support maternity service quality
      improvement: using Core Outcome Set methodology including a Delphi process: The
      Robson 10-groups classification system - all groups are needed.

PMID- 30302890
TI  - Comparison of outcomes between hemithyroidectomy alone and hemithyroidectomy with
      elective unilateral central neck dissection in patients with papillary thyroid
      microcarcinoma.
AB  - BACKGROUND: There have been arguments over the efficacy of elective unilateral
      central neck dissection (CND) in patients with papillary thyroid carcinoma (PTC)
      <1 cm who underwent hemithyroidectomy. This study was designed to investigate
      locoregional recurrence and postoperative complications related to elective
      unilateral CND for papillary thyroid microcarcinoma (PTMC). METHODS: Five hundred
      thirty-seven patients who underwent hemithyroidectomy, with or without CND for
      PTMC, were included. We compared locoregional recurrence and postoperative
      complication rates between 138 patients who underwent hemithyroidectomy only (CND
      group) and 399 patients who underwent hemithyroidectomy with elective unilateral
      CND (CND+ group). RESULTS: Recurrence was observed in 32 patients. Twenty-two
      patients with recurrence were in the CND+ group and 10 were in the CND- group.
      Recurrence rate was not significantly different between the 2 groups (P = .434).
      CONCLUSION: Concomitant unilateral elective CND did not enhance outcomes of
      hemithyroidectomy for the treatment of PTMC.

PMID- 30302892
TI  - CO2 embolus during transanal TME; thoughts on aetiology.
AB  - We describe a series of three carbon dioxide (CO2) emboli that have been
      encountered over a period of eighteen months during the perineal dissection of
      the transanal total mesorectal excision (taTME) in our unit. It is a concerning
      phenomenon, particularly as the risk of CO2 embolism in the setting of
      laparoscopic transabdominal surgery is negligible. This article is protected by
      copyright. All rights reserved.

PMID- 30302893
TI  - Framework for microRNA variant annotation and prioritization using human
      population and disease datasets.
AB  - MicroRNA (miRNA) expression is frequently deregulated in human disease, in
      contrast, disease-associated miRNA mutations are understudied. We developed
      Annotative Database of miRNA Elements, ADmiRE, which combines multiple existing
      and new biological annotations to aid prioritization of causal miRNA variation.
      We annotated 10,206 mature (3,257 within seed region) miRNA variants from
      multiple large sequencing datasets including gnomAD (15,496 genomes; 123,136
      exomes). The pattern of miRNA variation closely resembles protein-coding exonic
      regions, with no difference between intragenic and intergenic miRNAs (P = 0.56),
      and high confidence miRNAs demonstrate higher sequence constraint (P < 0.001).
      Conservation analysis across 100 vertebrates identified 765 highly conserved
      miRNAs that also have limited genetic variation in gnomAD. We applied ADmiRE to
      the TCGA PanCancerAtlas WES dataset containing over 10,000 individuals across 33
      adult cancers and annotated 1,267 germline (rare in gnomAD) and 1,492 somatic
      miRNA variants. Several miRNA families with deregulated gene expression in cancer
      have low levels of both somatic and germline variants, e.g., let-7 and miR-10. In
      addition to known somatic miR-142 mutations in hematologic cancers, we describe
      novel somatic miR-21 mutations in esophageal cancers impacting downstream miRNA
      targets. Through the development of ADmiRE, we present a framework for annotation
      and prioritization of miRNA variation in disease datasets.

PMID- 30302894
TI  - Mutagenesis of kiwifruit CENTRORADIALIS-like genes transforms a climbing woody
      perennial with long juvenility and axillary flowering into a compact plant with
      rapid terminal flowering.
AB  - Annualization of woody perennials has the potential to revolutionize the breeding
      and production of fruit crops and rapidly improve horticultural species.
      Kiwifruit (Actinidia chinensis) is a recently domesticated fruit crop with a
      short history of breeding and tremendous potential for improvement. Previously,
      multiple kiwifruit CENTRORADIALIS (CEN)-like genes have been identified as
      potential repressors of flowering. In this study, CRISPR/Cas9- mediated
      manipulation enabled functional analysis of kiwifruit CEN-like genes AcCEN4 and
      AcCEN. Mutation of these genes transformed a climbing woody perennial, which
      develops axillary inflorescences after many years of juvenility, into a compact
      plant with rapid terminal flower and fruit development. The number of affected
      genes and alleles and severity of detected mutations correlated with the
      precocity and change in plant stature, suggesting that a bi-allelic mutation of
      either AcCEN4 or AcCEN may be sufficient for early flowering, whereas mutations
      affecting both genes further contributed to precocity and enhanced the compact
      growth habit. CRISPR/Cas9-mediated mutagenesis of AcCEN4 and AcCEN may be a
      valuable means to engineer Actinidia amenable for accelerated breeding, indoor
      farming and cultivation as an annual crop.

PMID- 30302895
TI  - Adjusting the structure and luminescence properties of Sr2-x Bax MgAl22 O36 :Eu2+
      phosphors by Sr:Ba ratio.
AB  - Europium ion (Eu2+ )-doped phosphors exhibit adjustable photoluminescence due to
      the sensitivity of their luminescence to the local environment. It is of great
      significance to adjust the luminescence of Eu2+ by changing their local
      environment in the host. In this work, we investigated the effect of
      strontium/barium (Sr:Ba) ratio on the structure and luminescence properties of
      Sr2-x Bax MgAl22 O36 :Eu2+ phosphors. Our investigation indicates that with the
      decrease of Sr:Ba ratio, the matrix lattice gradually expands and the peak
      wavelength for the luminescence of Eu2+ presents an obvious blue shift. The
      occupancy of Eu2+ was analyzed and the reason for the blue shift was explained.
      Thermal stability for the luminescence of Eu2+ can also be adjusted by changing
      the Sr:Ba ratio. This work has a positive effect on the regulation of the
      emission of phosphors and the improvement of thermal stability, which will
      promote the application of Sr2-x Bax MgAl22 O36 :Eu2+ phosphors in the field of
      white light emitting diodes.

PMID- 30302896
TI  - A preliminary investigation into the prognostic relevance of symmetric
      dimethylarginine in critically ill dogs.
AB  - OBJECTIVE: To determine if there is an association between the concentration of
      symmetric dimethylarginine (SDMA) in dogs measured at the time of admission with
      the severity of critical illness and short-term mortality. DESIGN: This
      prospective observational study recruited critically ill dogs with heterogeneous
      diagnoses and then classified their disease severity using the acute patient
      physiologic and laboratory evaluation complete score as having either a good
      (<30) or poor (>=30) prognosis. SETTING: This study was conducted at Ross
      University Veterinary Clinic between January and November 2015. ANIMALS: After
      exclusion of dogs diagnosed with acute kidney injury, 22 critically ill dogs and
      7 control dogs were included in the study. INTERVENTIONS: Each dog was assigned
      an acute patient physiologic and laboratory evaluation score calculated by the
      summation of individual scores allocated to selected clinical, focused assessment
      by sonography, hematological, and biochemistry results. Plasma SDMA
      concentrations were measured for all dogs at the time of admission. MEASUREMENT
      AND MAIN RESULTS: There was no difference identified in SDMA concentrations
      between dogs with a severe category of disease as compared to mild to moderate
      category, or critically ill dogs compared to control dogs. There was also no
      difference identified in SDMA concentrations in survivors as compared to
      nonsurvivors. Similarly, SDMA concentration was not higher in nonsurvivors than
      in survivors (P = 0.968). In this population of dogs, SDMA was not a prognostic
      indicator. CONCLUSION: Further work may be warranted in specific populations of
      animals but based upon this work SDMA is likely of little relevance.

PMID- 30302897
TI  - Thermoluminescence properties of La3+ , Gd3+ ,Dy3+ and Ho3+ co-doped MgAl2 Si2 O8
      :Mn4.
AB  - Thermoluminescence properties of Mn4+ -doped and La3+ , Gd3+ , Dy3+ and Ho3+ co
      doped MgAl2 Si2 O8 host phosphors were investigated in detailed and reported for
      the first time. The phosphors were exposed to beta- and alpha-irradiation and the
      glow curves appeared at 260-262 +/- 2 degrees C and 245-252 +/- 2 degrees C,
      respectively. Thermoluminescence analysis show that the main glow peaks actually
      consisted of three distinct peaks (P1 , P2 and P3 ). In addition, all the
      phosphors had a main peak, and many satellite peaks also appeared up to 200
      degrees C. Moreover, it was observed that La3+ , Gd3+ , Dy3+ and Ho3+ dopants in
      MgAl2 Si2 O8 Mn4+ phosphor can change the thermoluminescence peak intensities,
      but they did not cause any new glow peak. In addition, when alpha-irradiation was
      used, the glow peaks were shift to a lower temperature region. Kinetic parameters
      of P1 , P2 and P3 were calculated, and it was found that P1 and P3 had first
      order kinetics and P2 had general-order kinetic parameters. In addition, it was
      found that when the easy and convenient annealing procedure was applied to the
      phosphorus, the thermoluminescence signal was measured as stable over many
      repetitions. The dose sensitivity, reproducibility and fading features of the
      powdered phosphors were investigated and computerized glow curve deconvolution
      analysis was also performed. Results showed that thermoluminescence properties of
      these materials were good but the fading reliabilities were poor and therefore
      the sintered or single crystal forms should be preferred for their better fading
      properties.

PMID- 30302898
TI  - Comparison of radiopacity of current restorative CAD/CAM blocks with digital
      radiography.
AB  - OBJECTIVE: While the radiopacity of restorative material affects the radiographic
      diagnosis of the teeth, there is no data about the radiopacity of current
      restorative computer-aided design (CAD)/computer-aided manufacturing (CAM)
      materials. Therefore, the present study compared the radiopacity values of
      current restorative CAD/CAM blocks to facilitate the material choice within such
      a wide variety of materials. MATERIALS AND METHODS: Specimens were prepared from
      13 different restorative CAD/CAM blocks to compare with enamel and dentin. The
      specimens placed on the occlusal phosphor plate were imaged with aluminum step
      wedge and tooth section. The radiopacity values were calculated using the Image J
      program. The radiopacity values of the specimens were converted to mmAl values
      with the Curve Expert 1.4 program. RESULTS: The difference between the
      radiopacity values of dentin and e.max CAD was not significant, however, they
      exhibited a significant difference from the other 14 groups (P < .05). Enamel and
      Obsidien, Suprinity, and Celtra Duo had greater radiopacity values with
      significant differences from the other 12 materials whereas the difference within
      these groups was not significant (P > .05). CONCLUSIONS: The evaluated
      restorative CAD/CAM materials have significantly different radiopacity values.
      Among these permanent restoration blocks, the highest radiopacity value was
      observed in Celtra Duo, the lowest in Block HC. CLINICAL SIGNIFICANCE: Cerasmart,
      Lava Ultimate, Obsidian, Vita Suprinity, Celtra Duo Blocks have adequate
      radiopacity for inlay, onlay and crown restorations, however, the use of Vita
      Enamic, Vita Mark II, GC LRF blocks and the others which have lower radiopacity
      value than dentin for the same kind of restorations depend on the radiopacity of
      the luting cement for the purpose of recurrent caries detection.

PMID- 30302899
TI  - Schaaf-Yang syndrome overview: Report of 78 individuals.
AB  - Schaaf-Yang Syndrome (SYS) is a genetic disorder caused by truncating pathogenic
      variants in the paternal allele of the maternally imprinted, paternally expressed
      gene MAGEL2, located in the Prader-Willi critical region 15q11-15q13. SYS is a
      neurodevelopmental disorder that has clinical overlap with Prader-Willi Syndrome
      in the initial stages of life but becomes increasingly distinct throughout
      childhood and adolescence. Here, we describe the phenotype of an international
      cohort of 78 patients with nonsense or frameshift mutations in MAGEL2. This
      cohort includes 43 individuals that have been reported previously, as well as 35
      newly identified individuals with confirmed pathogenic genetic variants. We
      emphasize that intellectual disability/developmental delay, autism spectrum
      disorder, neonatal hypotonia, infantile feeding problems, and distal joint
      contractures are the most consistently shared features of patients with SYS. Our
      results also indicate that there is a marked prevalence of infantile respiratory
      distress, gastroesophageal reflux, chronic constipation, skeletal abnormalities,
      sleep apnea, and temperature instability. While there are many shared features,
      patients with SYS are characterized by a wide phenotypic spectrum, including a
      variable degree of intellectual disability, language development, and motor
      milestones. Our results indicate that the variation in phenotypic severity may
      depend on the specific location of the truncating mutation, suggestive of a
      genotype-phenotype association. This evidence may be useful in both prenatal and
      pediatric genetic counseling.

PMID- 30302900
TI  - Diploid/triploid mixoploidy: A consequence of asymmetric zygotic segregation of
      parental genomes.
AB  - Triploidy is the presence of an extra haploid set of chromosomes and can exist in
      complete or mosaic form. The extra haploid set of chromosomes in triploid cells
      can be of maternal or paternal origin. Diploid/triploid mixoploidy is a unique
      form of triploid mosaicism that requires the aberrant segregation of entire
      parental genomes into distinct blastomere lineages (heterogoneic cell division)
      at the earliest zygotic divisions. Here we report on eight cases of
      diploid/triploid mixoploidy from our institution and conduct a comprehensive
      review of the literature. The parental origin of the extra set of chromosomes was
      determined in two cases; and, based on phenotypic evidence we propose the
      parental origin in the other cases. One case with complex mixoploidy appears to
      have a digynic origin in addition to the involvement of two different sperm. Of
      our eight cases, only one resulted in the birth of a live healthy child. The
      other pregnancies ended in miscarriage, elective termination of pregnancy,
      intrauterine fetal demise or neonatal death. A review of the literature and the
      results of our cases show that a preponderance of recognized cases of
      diploid/triploid mixoploidy has a digynic origin.

PMID- 30302901
TI  - Intralesional pentoxifylline injection in localized alopecia areata.
AB  - BACKGROUND: Alopecia areata (AA) is a common non-scarring autoimmune disease that
      affects hair-bearing areas. A variety of therapeutic options has been used for
      treating this disease such as corticosteroids, minoxidil, methotrexate,
      cyclosporine, and azathioprine. Intralesional triamcinolone acetonide (TRA)
      injection is considered the first-line treatment in localized alopecia areata
      involving <50% of the scalp; however, intralesional steroid injections are
      associated with a variety of side effects. OBJECTIVE: The aim of this study was
      to evaluate the efficacy of pentoxifylline (PTX) vs triamcinolone acetonide
      intralesional in localized AA. PATIENTS AND METHODS: The sample included 75
      patients (47 males and 28 females) aged 18-55 years, diagnosed as localized
      alopecia areata. The patients were treated by intralesional injection every three
      weeks up to five sessions. The patients were classified into three groups
      according to the used therapeutic modality. Group A: 25 patients treated by
      intralesional injection of TRA. Group B: 25 patients treated by combined
      intralesional injection of TRA and PTX injection. Group C: 25 patients treated by
      intralesional PTX injection. RESULTS: Both PTX and TRA intralesional injections
      were effective in the treatment of AA, but there was a statistically significant
      difference regarding the response to treatment between the three study groups (P
      value = 0.01). The highest response was reported in combined drug usage (TRA &
      PTX) followed by PTX alone and then TRA alone (72.0%, 60.0%, and 32.0%,
      respectively). CONCLUSION: Pentoxifylline intralesional injection is effective,
      easy to perform with little side effects for the treatment of localized alopecia
      areata.

PMID- 30302902
TI  - Short Panicle 3 controls panicle architecture by upregulating APO2/RFL and
      increasing cytokinin content in rice.
AB  - Inflorescence architecture is a major determinant of spikelet numbers per
      panicle, a key component of grain yield in rice. In this study, Short Panicle 3
      (SP3) was identified from a short panicle 3 (sp3) mutant in which T-DNA was
      inserted in the promoter of SP3, resulting in a knockdown mutation. SP3 encodes a
      DNA binding with one finger (Dof) transcriptional activator. Quantitative real
      time (qRT)-PCR and RNA in situ hybridization assays confirmed that SP3 is
      preferentially expressed in the young rice inflorescence, specifically in the
      branch primordial regions. SP3 acts as a negative regulator of inflorescence
      meristem abortion by upregulating APO2/RFL. SP3 both up- and down-regulates
      expression of genes involved in cytokinin biosynthesis and catabolism,
      respectively. Consequently, cytokinin concentrations are decreased in young sp3
      panicles, thereby leading to small panicles having fewer branches and spikelets.
      Our findings support a model in which SP3 regulates panicle architecture by
      modulating cytokinin homeostasis. Potential applications to rice breeding,
      through gene-editing of the SP3 promoter are assessed.

PMID- 30302903
TI  - Conventional and quantitative MRI in a novel feline model of demyelination and
      endogenous remyelination.
AB  - BACKGROUND: The feeding of irradiated food to healthy adult cats results in
      widespread, noninflammatory demyelination of the central nervous system (CNS); a
      return to a normal diet results in endogenous remyelination with functional
      recovery. This recently discovered, reversible disease might provide a compelling
      clinical neuroimaging model system for the development and testing of myelin
      directed MRI methods as well as future remyelination therapies. PURPOSE: Identify
      the noninvasive imaging characteristics of this new disease model and determine
      whether it features measurable changes on conventional and quantitative MRI.
      STUDY TYPE: Pilot study. ANIMAL MODEL: Ten adult cats at various stages of
      demyelinating disease induced by an irradiated diet (35-55 kGy), and during
      recovery following a return to a normal diet. FIELD STRENGTH/SEQUENCE:
      Conventional (T2 -weighted) and quantitative (diffusion tensor, magnetization
      transfer) at 3T. ASSESSMENT: MRI of the brain, optic nerves, and cervical spinal
      cord; a subset of diseased cats was euthanized for comparative histopathology.
      STATISTICAL TESTS: Descriptive statistics. RESULTS: Disease produced T2
      prolongation, progressing from patchy to diffuse throughout most of the cerebral
      white matter (eventually involving U-fibers) and spinal cord (primarily dorsal
      columns, reminiscent of subacute combined degeneration but without evidence of
      B12 deficiency). Magnetization transfer parameters decreased by 50-53% in
      cerebral white matter and by 25-30% in optic nerves and spinal cord dorsal
      columns. Fractional diffusion anisotropy decreased by up to 20% in pyramidal
      tracts, primarily driven by increased radial diffusivity consistent with axon
      preservation. Histopathology showed scattered myelin vacuolation of major white
      matter tracts as well as many thin myelin sheaths consistent with remyelination
      in the recovery phase, which was detectable on magnetization transfer imaging.
      DATA CONCLUSION: Feline irradiated diet-induced demyelination features
      noninvasively imageable and quantifiable demyelination and remyelination of the
      CNS. It is therefore a compelling clinical neuroimaging model system. LEVEL OF
      EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 30302904
TI  - Sulforaphane Normalizes Intestinal Flora and Enhances Gut Barrier in Mice with
      BBN-Induced Bladder Cancer.
AB  - SCOPE: Gut microbiota imbalance, inflammation, and gut barrier deficiency play an
      important role in carcinogenesis. Sulforaphane (SFN), an isothiocyanate found in
      cruciferous vegetables, has been proven to be highly effective in inhibiting
      cancer. The objective of this study is to investigate the potential roles of the
      gut microbiota in the inhibition of BBN-induced bladder cancer by SFN. METHODS
      AND RESULTS: N-butyl-N-(4-hydroxybutyl)-nitrosamine is used to induce bladder
      cancer in male C57BL/6 mice, with or without SFN for 23 weeks. SFN ameliorates
      the histological changes characteristic of bladder cancer, resulting in fewer
      submucosal capillaries. SFN normalizes gut microbiota dysbiosis in mice with BBN
      induced bladder cancer with a significant increase in Bacteroides fragilis and
      Clostridium cluster I. SFN also increases butyric acid levels in the mouse colon,
      and repairs the injury to the mucosal epithelium of the colon and cecum through
      the upregulation of the expression of tight junction proteins and GLP2. SFN
      greatly decreases the release of cytokines (IL-6) and secretory immunoglobulin A
      in the mice with bladder cancer. CONCLUSION: These results suggest that SFN
      protects against chemical-induced bladder cancer through normalizing the
      composition of gut microbiota and repairing the physiological destruction of the
      gut barrier, as well as decreasing inflammation and the immune response.

PMID- 30302905
TI  - Dysregulated homeostatic pathways in sarcopenia among frail older adults.
AB  - Sarcopenia, a core feature of the physical frailty syndrome, is characterized by
      multisystem physiological dysregulation. No study has explored qualitatively the
      hierarchical network of relationships among different dysregulated pathways
      involved in the pathogenesis of sarcopenia. We used 40 blood biomarkers belonging
      to community-dwelling prefrail and frail older persons to derive measures of
      multiple physiological pathways, and structural equation modeling to generate
      path network models of the multisystem physiological dysregulations associated
      with muscle mass and function (MMF). Insulin-leptin signaling and energy
      regulation, anabolic sex steroid regulation (testosterone, leptin), and tissue
      oxygenation (hemoglobin, red cell count) appear to be primary mediating factors
      exerting direct influences on MMF. There was additionally secondary mediatory
      involvement of myocyte- and adipocyte-derived cytokines, hypothalamic pituitary
      adrenal (HPA) stress hormones (cortisol, DHEAS), glomerular function, and immune
      cell regulatory and inflammatory cytokines and glycoproteins. We conclude that
      within a hierarchical network of multisystem physiological dysregulations in
      sarcopenia, dysregulated anabolic and catabolic pathways via sex steroids and
      insulin-leptin dual signaling and tissue hypoxemia are primary physiological
      dysregulations responsible for sarcopenia and frailty.

PMID- 30302906
TI  - Emphysematous gastritis in a cat.
AB  - OBJECTIVE: To describe the presentation, diagnosis, treatment, and outcome of a
      case of emphysematous gastritis (EG) in a cat. CASE SERIES SUMMARY: A 15-year-old
      female neutered domestic short-hair cat presented for a 4-month history of weight
      loss and intermittent vomiting. Clinicopathologic and imaging findings suggested
      an underlying primary gastrointestinal (GI) disease, as well as possible
      hepatobiliary disease. Two days following exploratory laparotomy to obtain GI and
      liver biopsies, the patient became septic and intracellular bacteria were present
      on cytology of peritoneal effusion. On radiographs, the stomach was markedly
      distended with fluid and contained a thin gas opacity surrounding the stomach
      wall. The patient was taken back to surgery to identify a source of sepsis. At
      surgery, the patient's stomach was firm and emphysematous on palpation but
      grossly appeared normal. There were no signs of dehiscence of the previous biopsy
      sites. Stomach biopsy confirmed the presence of intralesional Gram-positive rods,
      consistent with microbial EG, and a light growth of a Clostridium sp. was
      cultured from abdominal fluid, consistent with clostridial peritonitis. During a
      third surgery for suspected septic peritonitis, a jejunostomy tube was placed for
      postgastric enteral feeding. The patient ultimately survived to discharge and is
      clinically stable 10 months later. NEW/UNIQUE INFORMATION PROVIDED: EG is a rare
      but potentially fatal clinical entity in the human and veterinary literature with
      only 1 other case reported in cats. Though clostridial organisms have been
      reported in EG in people, this is the first implication of EG secondary to a
      Clostridium sp. in the cat. This is also the first report to document the use of
      a jejunostomy tube for postgastric enteral nutrition to treat EG in the
      veterinary literature.

PMID- 30302907
TI  - Characteristics of and current practice patterns of pacing for high-degree
      atrioventricular block after transcatheter aortic valve implantation in
      comparison to surgical aortic valve replacement.
AB  - OBJECTIVE: We aimed to investigate the current practice patterns of permanent
      pacing, especially the timing of implantation, for high-degree AV block (HDAVB)
      following transcatheter aortic valve implantation (TAVI) and surgical aortic
      valve replacement (SAVR). BACKGROUND: Comparative data regarding current practice
      patterns of permanent pacing for HDAVB between TAVI and SAVR is limited. METHODS:
      Using the National Inpatient Sample database, we identified patients who
      underwent TAVI or SAVR between 2012 and 2014. The incidence of HDAVB, the rate of
      permanent pacemaker implantation, and the timing of implantations were compared
      between TAVI and SAVR groups. RESULTS: We identified 33 690 and 202 110 patients
      who underwent TAVI and SAVR, respectively. HDAVB occurred in 3480 patients
      (10.3%) in the TAVI group and 11 405 patients (5.6%) in the SAVR group (P <
      0.001). Among the patients who developed HDAVB, patients in the TAVI group were
      more likely to undergo permanent pacemaker implantation than those in the SAVR
      group (74.1% vs 64.7%; P < 0.001). The median interval from TAVI to pacemaker
      implantation was 2 days (interquartile range 1-3 days) vs 5 days (interquartile
      range 3-7 days) from SAVR to pacemaker implantation (P < 0.001). Among the
      patients who developed HDAVB, TAVI was associated with higher rates of permanent
      pacemaker implantation after adjusting for other comorbidities (odds ratio
      1.41:95% confidence interval 1.13-1.77; P = 0.003). CONCLUSIONS: HDAVB occurred
      more commonly after TAVI compared to SAVR. HDAVB after TAVI compared to SAVR was
      associated with a higher rate of permanent pacemaker implantation at an earlier
      timing from the index procedure.

PMID- 30302908
TI  - Efficient Nanostructuring of Silicon by Electrochemical Alloying/Dealloying in
      Molten Salts for Improved Lithium Storage.
AB  - Application of nanostructured silicon (nSi) is significantly retarded by
      challenges in the production of affordable nSi. We herein report a high-yield
      (ca. 100 %) and low-energy (2 kWh Kg-nSi-1 ) nanostructuring of industrial
      microsized silicon (mSi) through a closed-loop electrochemical Mg
      alloying/dealloying in molten MgCl2 /NaCl/KCl at 773 K. The resulting nSi
      unexpectedly shows a salt-unwetted character, allowing an automatic separation
      from the melts. Thus water washing and accompanying oxidation of the nSi can be
      avoided. The final product has a nanoporous structure and comprises Si nanorods
      (ca. 30 nm in diameter) with an ultrathin oxide coating. It can be used for Li
      storage giving a combination of high initial coulombic efficiency, high specific
      capacity, and long cycling stability. This nanostructuring process consumes very
      few chemicals except for the mSi and produces almost zero waste.

PMID- 30302910
TI  - High false positive rate of white blood cells in urine samples of pregnant women
      may be caused by epithelial cells being misclassified by the sysmex UF-1000i
      urine flow cytometer.
AB  - BACKGROUND: The UF-1000i has been widely used in screening urinary sediments.
      However, the interference factor of the UF-1000i in the screening urinary
      sediments of pregnant women has not been reported. The aim of the study was to
      demonstrate that epithelial cells (ECs) cause a high false positive rate of white
      blood cells (WBCs) by the UF-1000i in pregnant women. METHODS: Urine samples were
      collected from 207 pregnant women. All samples were measured by the UF-1000i and
      a microscopic method. RESULTS: The areas under the curve (AUC) for WBC and EC
      counts were 0.837 (95% CI, 0.773-0.901) and 0.844 (95% CI, 0.785-0.903),
      respectively. The positive rates of the WBC and EC were 73.43% and 37.20%,
      respectively, by the UF-1000i, and they were 19.32% and 72.95% by the microscopic
      method. The positive predictive value, negative predictive value, false positive
      rates, and false negative rates by the UF-1000i were for WBC 25.66%, 98.18%,
      74.34%, and 1.82%, respectively, and for EC they were 96.1%, 40.77%, 3.9%, and
      59.23%, respectively. The coefficient of correlation R value was 0.503 (P < 0.01)
      between WBC by UF-1000i and EC by the microscopic method in WBC false positive
      samples. CONCLUSIONS: EC could be an interference factor for the UF-1000i in
      screening urinary WBC of pregnant women, and the high false positive rate for WBC
      may be caused by ECs being misclassified as WBCs by the UF-1000i.

PMID- 30302909
TI  - Five-year success rate of resin-bonded fixed partial dentures: A systematic
      review.
AB  - OBJECTIVES: To assess and compare the 5-year success rate of resin-bonded fixed
      partial dentures (RBFPDs) fabricated from different materials. METHODS: An
      electronic search on 3 databases from January 1965 to March of 2017 was done for
      human randomized clinical trials (RCTs), and prospective and retrospective cohort
      studies. The key words used in the search were: Bridge OR bridges OR fixed
      partial OR fixed dental AND resin bonded OR Maryland OR ceramic bonded. Quality
      assessment was done using the Newcastle-Ottawa scale. Success was defined as the
      RBFPDs remaining in situ and not having experienced debonding, biological
      failures, or mechanical failures at the examination visit. RESULTS: Meta analyses
      of the included studies showed an estimated 5-year success rate of 88.18% for the
      metal framework RBFPDs and 84.41% for the nonmetal framework RBFPDs. The
      estimated 5-year success rate for each nonmetal material category was 92.07% for
      zirconia, 94.26% for In-Ceram alumina, and 84.83% for fiber-reinforced composite.
      The failure rate was not statistically significant among the single, double, and
      multiple retainers RBFPDs (P > .05). Technical complications were the main reason
      for failures. CONCLUSION: The 5-year clinical performance of RBFPDs is similar to
      the performance of conventional fixed partial dentures (FPDs) and implant
      supported crowns. CLINICAL SIGNIFICANCE: Clinicians should consider using RBFPDs
      more often because their clinical performance is similar to the performance of
      conventional FPDs and implant-supported crowns.

PMID- 30302911
TI  - Mitochondrial Deformation During the Cardiac Mechanical Cycle.
AB  - Cardiomyocytes both cause and experience continual cyclic deformation. The exact
      effects of this deformation on the properties of intracellular organelles are not
      well characterized, although they are likely to be relevant for cardiomyocyte
      responses to active and passive changes in their mechanical environment. In the
      present study we provide three-dimensional ultrastructural evidence for
      mechanically induced mitochondrial deformation in rabbit ventricular
      cardiomyocytes over a range of sarcomere lengths representing myocardial tissue
      stretch, an unloaded "slack" state, and contracture. We also show structural
      indications for interaction of mitochondria with one another, as well as with
      other intracellular elements such as microtubules, sarcoplasmic reticulum and T
      tubules. The data presented here help to contextualize recent reports on the
      mechanosensitivity and cell-wide connectivity of the mitochondrial network and
      provide a structural framework that may aide interpretation of mechanically
      regulated molecular signaling in cardiac cells. Anat Rec, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30302912
TI  - Conformational Selection of a Polyproline Peptide by Ebola Virus VP30.
AB  - An adaptive temperature-based replica-exchange simulation of a peptide extracted
      from the Ebola virus nucleoprotein containing a polyproline sequence motif is
      reported. The simulation results of applying the CHARMM36m force field with a
      generalized Born solvent model is presented. Conformational heterogeneity is
      described by potentials of mean force (PMFs) for a set of reaction coordinates
      that define the topological fold space. Starting from an extended backbone
      conformation of the peptide observed in an X-ray crystallographic assembly with
      the Ebola virus protein VP30, the PMFs report a conformational landscape
      populated by chain excursions to collapsed states with limited transitions to
      either an extended fold or a canonical polyproline type II helix. Clustering of
      the conformations and applying an elastic network interpolation model yield a
      multistep pathway of conformational selection that minimizes the net transition
      state cost from the population hub to the bound state. Related difference between
      the pathway endpoints taken from the PMFs reveal a significant free-energy
      penalty in reaching a population shift. To evaluate sequence fitness of the Ebola
      virus peptide in generating probability distributions, two human sequence
      variants are modeled and are found to produce profiles that show extensive
      deviations, thus suggesting either dissimilar binding mechanisms or the lack of
      recognition by VP30.

PMID- 30302913
TI  - Editorial: 150 Years of the Technische Universitat Munchen: Innovation since
      1868.
AB  - "... On Easter Sunday 1868, the decree founding the Polytechnische Hochschule
      Munchen (today's Technische Universitat Munchen; TUM) was signed by the 23-year
      old Ludwig II, King of Bavaria. Entrepreneurial spirit has been a hallmark of the
      TUM from the start, and it was the first German university to have a branch
      abroad. Interdisciplinary research is key, not least in the Department of
      Chemistry ..." Read more in the Guest Editorial by Wolfgang A. Herrmann.

PMID- 30302914
TI  - Application of coordination agent in high-speed counter-current chromatography
      for the preparative separation and isolation ginkgolic acids from the sarcotesta
      of Ginkgo biloba L.
AB  - An efficient coordination high-speed counter-current chromatography method for
      the preparative separation of ginkgolic acids from the sarcotesta of Ginkgo
      biloba L was developed. The type, concentration, and mechanism of the
      coordination agent were investigated. Following the use of four types of metal
      salts including silver nitrate, copper chloride, ferric chloride, and aluminium
      nitrate, n-heptane/ethyl acetate/methanol/acetic acid 5:4:1:1, v/v with 0.20
      mol/L silver nitrate as the coordination agent was chosen as the optimum two
      phase solvent system. Five main ginkgolic acids including C13:0, C15:0, C15:1,
      C17:1, and C17:2 were successfully separated with purities greater than 98%. The
      sample loading was 500 mg, the flow-rate was 2.0 mL/min, rotation speed was 800
      rpm and temperature was 20 degrees C. The structures of the separated ginkgolic
      acids were identified by comparison with standard samples and electrospray
      ionization mass spectrometry. The introduction of coordination chemistry in high
      speed counter-current chromatography is novel and effective for the preparative
      separation and isolation of ginkgolic acids from the sarcotesta of Ginkgo biloba
      L and could also be applied to separate compounds which form coordination bonds
      in other complex natural products.

PMID- 30302915
TI  - The Impact of Autonomy-Framed and Control-Framed Implementation Intentions on
      Snacking Behaviour: The Moderating Effect of Eating Self-Efficacy.
AB  - BACKGROUND: Autonomy-supportive implementation intention exercises have been
      shown to facilitate goal-directed behaviour (Koestner et al., ). The current
      study explored whether eating self-efficacy moderated the impact of autonomy
      framed versus control-framed implementation intentions to reduce high-calorie
      snack intake. METHODS: The study employed a randomised prospective design,
      involving two waves of data collection conducted in 2016. At Time 1, UK
      participants (N = 300) completed an online questionnaire which asked them to
      report their snacking behaviour over the previous 7 days. Participants were
      subsequently asked to form either an autonomy-framed implementation intention or
      a control-framed implementation intention. Seven days later, participants
      reported their consumption of high-calorie snacks and completed a measure of
      eating self-efficacy. RESULTS: Hierarchical multiple regression analysis revealed
      that eating self-efficacy moderated the effects of implementation intention
      framing. Autonomy-framed implementation intentions had a greater impact on the
      avoidance of snacking for high eating self-efficacy participants than did control
      framed implementation intentions. In contrast, for low eating self-efficacy
      participants, control-framed implementation intentions had more impact than did
      autonomy-framed implementation intentions. CONCLUSIONS: The results suggest that
      if implementation intentions to promote healthy diet are to be effective, the
      role of eating self-efficacy should be considered, and the design of
      interventions adapted accordingly.

PMID- 30302916
TI  - Evaluation of Mental Health First Aid skills in an Australian university
      population.
AB  - AIM: University students have high rates of mental health problems; however, most
      delay or fail to seek help altogether. Tertiary settings can offer educational
      and social programmes to increase mental health awareness and in turn increase
      the number of students seeking help for their problems. This study aimed to
      explore students' and staffs' knowledge of mental health issues, confidence to
      intervene and application of skills following Mental Health First Aid (MHFA)
      training. METHODS: Students and staff at an Australian university who had
      completed MHFA training in the previous 24 months were invited to complete a
      validated online questionnaire. RESULTS: Of the 566 eligible participants, 107
      (19%) completed the questionnaire. The majority (65%) had applied their skills to
      someone in need, with the highest number applying it to students. Notably, of
      those who had applied their skills 23 participants (33%) had applied them in a
      crisis situation, the most common being panic attacks followed by suicidal
      thoughts. Although most (98%) applied their skills in a face-to-face capacity,
      53% also reported assisting someone via electronic mediums and social media. The
      mean score for the literacy test was considered high, 12/16 (SD = 1.7) for
      students and 13/16 (SD = 2.5) for staff. The majority (94%) reported more
      confidence in providing support following training. CONCLUSION: This study
      demonstrated that MHFA training on a university campus is associated with a high
      level of knowledge, confidence to intervene and apply MHFA skills to assist a
      student or friend in need, potentially impacting their long-term health outcomes
      and future professional careers.

PMID- 30302917
TI  - The utility of a smartphone-enabled ophthalmoscope in pre-clinical fundoscopy
      training.

PMID- 30302918
TI  - Creativity in persons at-risk for bipolar disorder-A pilot study.
AB  - AIM: The association between bipolar disorder and creativity may be related to
      symptoms of the disorder itself or personality traits present before the onset.
      To further explore the relationship between creativity and clinical risk for
      bipolar disorder, creativity among individuals with a history of depressive
      disorder and varying risk for future (hypo-)manic episodes was assessed and
      compared. METHODS: Thirty-eight participants completed the diagnostic process,
      including Structured Clinical Interview for Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition (DSM-IV) Diagnosis, Hamilton Depression Scale
      and Young Mania Rating Scale. The early detection tools Bipolar Prodrome Symptom
      Interview and Scale-Prospective (BPSS-P), Early Phase Inventory for Bipolar
      Disorders (EPIbipolar) and bipolar-at-risk-(BAR) criteria were used to assign
      participants into different at-risk groups. Assessment of creativity included
      Barron-Welsh Art Scale (BWAS) and Creative Achievement Questionnaire (CAQ).
      Scores were compared between low- and high-risk groups for the development of
      bipolar disorder. RESULTS: Participants meeting BAR criteria scored significantly
      higher on the BWAS than the non-BAR group (P = 0.03). EPIbipolar groups did not
      differ significantly in creativity scores. Participants with mood swings,
      especially when associated with increased activity and euphoric features, had
      significantly higher BWAS scores compared to individuals without mood swings (P =
      0.04). Sleep disturbances, substance abuse, anxiety, ADHD and behavioural
      disturbances in childhood or adolescence had no effect on creativity level or
      achievement scores. Generalisability was reduced by small sample size and
      inclusion of depressive participants only considered at-risk for bipolar
      disorder. CONCLUSIONS: There is evidence of increased creativity, but not of
      higher creative achievements, in persons at-risk of bipolar disorder. Mood swings
      are strongly associated with creativity.

PMID- 30302920
TI  - Validation of Delay-Multiply-and-Standard-Deviation Weighting Factor for Improved
      Photoacoustic Imaging of Sentinel Lymph Node.
AB  - Delay-and-sum (DAS) is one of the most common algorithms used to construct the
      photoacoustic images due to its low complexity. However, it results in images
      with high sidelobes and low resolution. Delay-and-standard-deviation (DASD)
      weighting factor can improve the contrast of the images compared to DAS. However,
      it still suffers from high sidelobes. In this work, a new weighting factor, named
      delay-multiply-and-standard-deviation (DMASD) is introduced to enhance the
      contrast of the reconstructed images compared to other mentioned methods. In the
      proposed method, the standard deviation of the mutual multiplied delayed signals
      are calculated, normalized and multiplied to DAS beamformed data. The results
      show that DMASD improves the signal-to-noise-ratio about 19.29 dB and 7.3 dB
      compared to DAS and DASD, respectively, for invivo imaging of the sentinel lymph
      node. Moreover, the contrast-ratio is improve by the DMASD about 23.61 dB and
      10.81 dB compared to DAS and DASD, respectively. This article is protected by
      copyright. All rights reserved.

PMID- 30302919
TI  - Bone health in chronic kidney disease-mineral and bone disorder: a clinical case
      seminar and update.
AB  - The metabolic abnormalities affecting bone in the setting of chronic kidney
      disease (CKD) are complex with overlapping and interacting aetiologies and have
      challenging diagnostic and management strategies. Disturbances in calcium,
      phosphate, fibroblast growth factor 23, parathyroid hormone concentrations and
      vitamin D deficiency are commonly encountered and contribute to the clinical
      syndromes of bone disorders in CKD, including hyperparathyroidism, osteomalacia,
      osteoporosis and adynamic bone disease. Mineral and bone abnormalities may also
      persist or arise de novo post-renal transplantation. The Kidney Disease Improving
      Global Outcomes organisation describes these mineral metabolism derangements and
      skeletal abnormalities as 'CKD Mineral and Bone Disorder'. Patients with this
      disorder have an increased risk of fracture, cardiovascular events and overall
      increased mortality. In light of the recently updated 2017 guidelines from the
      Kidney Disease Improving Global Outcomes, we present a clinical case-based
      discussion to highlight the complexities of investigating and managing the bone
      health of patients with CKD with a focus on these updates.

PMID- 30302921
TI  - Retrospective evaluation of the effect of intravenous fluid administration on
      development of postoperative reflux in horses with colic (2004-2012): 194 horses.
AB  - OBJECTIVE: To evaluate the role of intravenous fluid volume and electrolyte
      supplementation on the development of postoperative reflux (POR) in horses
      undergoing celiotomy for colic. DESIGN: Case-control study spanning 2004-2012 for
      horses undergoing celiotomy for colic. SETTING: University teaching hospital.
      ANIMALS: Sixty-seven client-owned horses >1 year of age with POR were each
      matched to 2 controls with similar surgical lesions that did not demonstrate POR.
      MEASUREMENTS AND MAIN RESULTS: Survival was significantly lower in cases (65.7%)
      than controls (96.1%). Factors found to be associated with POR included decreased
      net fluid volume administered on day 1 postoperatively, increased age, and
      performing a resection and anastomosis. Mean time until onset of POR was 20.4
      hours postoperatively. PCV was significantly higher immediately following surgery
      and at 24 hours postoperatively in horses that developed POR compared with
      matched controls. There was no association between electrolyte values at
      presentation or administration of potassium, calcium, or magnesium in the
      postoperative period and the subsequent development of reflux. CONCLUSIONS: In
      the perioperative period, IV fluid volume overload and electrolyte abnormalities
      were not contributing factors in the development of POR in this population of
      surgical colic patients. Close postoperative monitoring with consideration and
      correction of pre- and postoperative fluid deficits is recommended.

PMID- 30302923
TI  - Super-achromatic optical coherence tomography capsule for ultrahigh-resolution
      imaging of esophagus.
AB  - Endoscopic optical coherence tomography (OCT) is a noninvasive technology
      allowing for imaging of tissue microanatomies of luminal organs in real time.
      Conventional endoscopic OCT operates at 1300 nm wavelength region with a
      suboptimal axial resolution limited to 8-20 MUm. In this paper, we present the
      first ultrahigh-resolution tethered OCT capsule operating at 800 nm and offering
      about 3- to 4-fold improvement of axial resolution (plus enhanced imaging
      contrast). The capsule uses diffractive optics to manage chromatic aberration
      over a full ~200 nm spectral bandwidth centering around 830 nm, enabling to
      achieve super-achromaticity and an axial resolution of ~2.6 MUm in air. The
      performance of the OCT capsule is demonstrated by volumetric imaging of swine
      esophagus ex vivo and sheep esophagus in vivo, where fine anatomic structures
      including the sub-epithelial layers are clearly identified. The ultrahigh
      resolution and excellent imaging contrast at 800 nm of the tethered capsule
      suggest the potential of the technology as an enabling tool for surveillance of
      early esophageal diseases on awake patients without the need for sedation.

PMID- 30302924
TI  - Imaging phenotype of multiple mitochondrial dysfunction syndrome 2, a rare BOLA3
      associated leukodystrophy.
AB  - Multiple mitochondrial dysfunction syndrome (MMDS) is a rare disorder of systemic
      energy metabolism associated with mutations in genes having a vital role in
      production of iron-sulfur clusters, important for the normal maturation of
      lipoate-containing 2-oxoacid dehydrogenases and for the assembly of the
      mitochondrial respiratory chain complexes. MMDS 2 associated with BOLA3 mutation
      presents in early infancy and is characterized by developmental regression,
      severe encephalopathy, optic atrophy, and cardiomyopathy. Neuroimaging phenotype
      associated with MMDS 2 has never been described in its entirety in literature,
      with few reported cases till date. None of the published cases mention findings
      demonstrated in our case, a proband with biallelic BOLA3 variants, such as
      necrotic/cavitary lesions within the centrum semiovale, restricted diffusivity
      within the white matter, areas of central enhancement within the centrum
      semiovale presumably related to leakage of contrast within the necrotic center,
      enhancement of bilateral optic nerves, and markedly elevated lactate on magnetic
      resonance spectroscopy.

PMID- 30302922
TI  - CTHRC1 overexpression predicts poor survival and enhances epithelial-mesenchymal
      transition in colorectal cancer.
AB  - Collagen triple helix repeat containing (CTHRC1), which was identified as a
      cancer-related factor, is a promigratory protein involved in multiple processes,
      including vascular remodeling, antifibrosis, metabolism, bone formation, and
      cancer. In this study, we aimed to investigate the clinical significance and
      possible role of CTHRC1 in the process of epithelial-mesenchymal transition (EMT)
      in colorectal cancer (CRC). Here, we revealed that CTHRC1 mRNA and protein levels
      are both upregulated in CRC tissues compared with those of paired noncancerous
      tissues. Moreover, the overexpression of CTHRC1 correlated with poor prognosis in
      patients with CRC (especially colon cancer). Furthermore, we showed that CTHRC1
      induced EMT and promoted cell motility in CRC cells. Importantly, we demonstrated
      that CTHRC1 promoted EMT by activating transforming growth factor-beta (TGF-beta)
      signaling, revealing a possible effective therapeutic treatment for patients with
      CRC.

PMID- 30302925
TI  - Physical activity and exercise as a universal depression prevention in young
      people: A narrative review.
AB  - AIM: The aim of this narrative summary was to examine the efficacy of physical
      activity and exercise as a universal prevention for depression in young people.
      METHODS: We conducted a search of the literature in the open-access evidence
      database of controlled trials and systematic reviews in youth mental health, an
      initiative between Orygen, The National Centre of Excellence in Youth Mental
      Health and headspace, National Youth Mental Health Foundation. In April 2018, we
      searched for all papers published between 1980 and 2017 relating to "Depressive
      Disorder" under the "Universal Prevention" illness stage and classified as
      "Physical activity/Exercise" under the treatment/intervention classification.
      Systematic reviews, randomized control trials (RCTs) and controlled clinical
      trials were all included. RESULTS: A total of 11 papers were returned. Three of
      these studies were observational and eight studies were controlled trials. The
      reviewed studies indicate that exercise and physical activity might be an
      effective universal depression prevention intervention for young people. Three of
      the controlled studies had a passive control group or no control group and only
      one study had longer-term follow-up. No trial used a longitudinal design to
      determine if interventions prevent the onset of new cases of depression.
      CONCLUSIONS: The studies reviewed in the current review demonstrate a
      bidirectional relationship between physical activity, exercise and adolescent
      mental health. The results of the current review suggest that physical activity
      and exercise programs designed to increase the level of activity in young people
      should be implemented to be attractive and achievable to young people that may
      have poor psychological health.

PMID- 30302926
TI  - Author's reply re: Clindamycin to reduce preterm birth in a low resource setting:
      a randomised placebo-controlled clinical trial.

PMID- 30302927
TI  - Whom do we serve?

PMID- 30302929
TI  - Genital infection in early pregnancy: to treat or not to treat, that is the
      question.

PMID- 30302930
TI  - Fetal imaging: past, present, and future. A journey of marvel.

PMID- 30302931
TI  - Re: Clindamycin to reduce preterm birth in a low resource setting: a randomised
      placebo-controlled clinical trial.

PMID- 30302933
TI  - Application of the uridine auxotrophic host and synthetic nucleosides for a rapid
      selection of hydrolases from metagenomic libraries.
AB  - A high-throughput method (>= 106 of clones can be analysed on a single agar
      plate) for the selection of ester-hydrolysing enzymes was developed based on the
      uridine auxotrophy of Escherichia coli strain DH10B DeltapyrFEC and the acylated
      derivatives 2',3',5'-O-tri-acetyluridine and 2',3',5'-O-tri-hexanoyluridine as
      the sole source of uridine. The proposed approach permits the selection of
      hydrolases belonging to different families and active towards different
      substrates. Moreover, the ester group of the substrate used for the selection, at
      least partly, determined the specificity of the selected enzymes.

PMID- 30302932
TI  - Proceedings of the fifth international RASopathies symposium: When development
      and cancer intersect.
AB  - This report summarizes and highlights the fifth International RASopathies
      Symposium: When Development and Cancer Intersect, held in Orlando, Florida in
      July 2017. The RASopathies comprise a recognizable pattern of malformation
      syndromes that are caused by germ line mutations in genes that encode components
      of the RAS/mitogen-activated protein kinase (MAPK) pathway. Because of their
      common underlying pathogenetic etiology, there is significant overlap in their
      phenotypic features, which includes craniofacial dysmorphology, cardiac,
      cutaneous, musculoskeletal, gastrointestinal and ocular abnormalities,
      neurological and neurocognitive issues, and a predisposition to cancer. The RAS
      pathway is a well-known oncogenic pathway that is commonly found to be activated
      in somatic malignancies. As in somatic cancers, the RASopathies can be caused by
      various pathogenetic mechanisms that ultimately impact or alter the normal
      function and regulation of the MAPK pathway. As such, the RASopathies represent
      an excellent model of study to explore the intersection of the effects of
      dysregulation and its consequence in both development and oncogenesis.

PMID- 30302934
TI  - Dynamic visualization of the recovery of mouse hepatobiliary metabolism to
      acetaminophen-overdose damage.
AB  - Acetaminophen (APAP) overdose is one of the world's leading causes of drug
      induced hepatotoxicity. Although traditional methods such as histological imaging
      and biochemical assays have been successfully applied to evaluate the extent of
      APAP-induced liver damage, detailed effect of how APAP overdose affect the
      recovery of hepatobiliary metabolism remains unclear.is not completely
      understood. In this work, we used intravital multiphoton microscopy to image and
      quantify hepatobiliary metabolism of the probe 6-carboxyfluorescein diacetate (6
      CFDA) in APAP-overdose mice. We analyzed hepatobiliary metabolism for up to 7
      days following the overdose and found that the excretion of the probe molecule
      was the most rapid one day following APAP overdose and slowed down on Days 2 and
      3. On Day 7, probe excretion capability has exceeded that of the normal mice,
      suggesting that newly regenerated hepatocytes have higher metabolic capabilities.
      Our approach may be further developed applied to studying drug-induced
      hepatotoxicity in vivo. This article is protected by copyright. All rights
      reserved.

PMID- 30302935
TI  - Retrospective evaluation of 4 methods for outcome prediction in overt
      disseminated intravascular coagulation in dogs (2009-2014): 804 cases.
AB  - OBJECTIVE: The clinical diagnosis of disseminated intravascular coagulation (DIC)
      in dogs is challenging. It was hypothesized that dogs with laboratory
      abnormalities consistent with overt DIC have increased mortality and hence
      survival could be used to evaluate the performance of DIC scoring systems. Four
      DIC scoring systems were compared in clinically ill dogs: The International
      Society of Thrombosis and Haemostasis (ISTH) score; a previously published
      veterinary DIC score; a system using in-house reference intervals (RIs) for
      coagulation assays; and the published veterinary DIC score modified by use of in
      house RI values. DESIGN: Retrospective cohort study. SETTING: University teaching
      hospital. ANIMALS: Eight hundred four client-owned dogs with underlying disorders
      associated with DIC. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical
      records were reviewed to identify dogs for which a coagulation panel consisting
      of coagulation times, D-dimer concentration, antithrombin activity, fibrinogen
      concentration, and platelet count had been analyzed. Four methods for overt DIC
      scoring were then applied, and the ability of these scores to predict mortality
      was evaluated. Use of institution RIs for diagnosis of overt DIC provided the
      most accurate prognostic assessment. A score based on abnormalities in 3 of 6
      parameters to identify overt DIC was 72.7% sensitive and 80.9% specific for
      mortality and was accurate in 78.4% of cases. The mortality rate of dogs
      diagnosed with overt DIC via this method was 62.5%, compared to 12.9% in the dogs
      not in overt DIC, a relative risk of nonsurvival of 4.84 (95% confidence interval
      3.80-6.16). CONCLUSIONS: In dogs at-risk for DIC, an in-house RI scoring system
      accurately predicted mortality. With further prospective validation, this system
      holds promise as a diagnostic tool for consistent characterization of overt DIC
      in clinical studies and clinical practice.

PMID- 30302936
TI  - Efficacy and safety of azilsartan medoxomil/chlortalidone fixed-dose combination
      in hypertensive patients uncontrolled on azilsartan medoxomil alone: A randomized
      trial.
AB  - Patients with grade 2-3 essential hypertension and postplacebo mean clinic
      systolic blood pressure (SBP) 160-190 mm Hg and 24-hour SBP 140-175 mm Hg by
      ambulatory blood pressure monitoring (ABPM) received 40 mg azilsartan medoxomil
      (AZL-M) monotherapy for 4 weeks. "Nonresponders" were then randomized to 8 weeks
      of double-blind treatment with AZL-M 40 mg, AZL-M/chlortalidone (CLD) 40/25, or
      AZL-M/CLD 40/12.5 mg. After 8 weeks, mean clinic SBP change was -21.1 (+/-1.04)
      mm Hg for AZL-M/CLD 40/25 mg, -15.8 (+/-1.08) mm Hg for AZL-M/CLD 40/12.5 mg, and
      -6.4 (+/-1.05) mm Hg for AZL-M 40 mg (P < 0.001 for both AZL-M/CLD vs AZL-M,
      ANCOVA). Drug discontinuation rates were 8.9% (AZL-M/CLD 40/25 mg), 7.5% (AZL-M
      40 mg), and 3.9% (AZL-M/CLD 40/12.5 mg). Creatinine increased in 8.1% (AZL-M/CLD
      40/25), 3.1% (AZL-M/CLD 40/12.5 mg), and 3.0% (AZL-M 40 mg) of patients. AZL
      M/CLD was effective and well tolerated in patients not achieving blood pressure
      targets with AZL-M.

PMID- 30302937
TI  - Concise Reviews: Stem Cells and Kidney Regeneration: An Update.
AB  - Significant progress has been made to advance stem cell products as potential
      therapies for kidney diseases: various kinds of stem cells can restore renal
      function in preclinical models of acute and chronic kidney injury. Nonetheless
      this literature contains contradictory results, and for this reason, we focus
      this review on reasons for apparent discrepancies in the literature, because they
      contribute to difficulty in translating renal regenerative therapies. Differences
      in methodologies used to derive and culture stem cells, even those from the same
      source, in addition to the lack of standardized renal disease animal models (both
      acute and chronic), are important considerations underlying contradictory results
      in the literature. We propose that harmonized rigorous protocols for
      characterization, handling, and delivery of stem cells in vivo could
      significantly advance the field, and present details of some suggested approaches
      to foster translation in the field of renal regeneration. Our goal is to
      encourage coordination of methodologies (standardization) and long-lasting
      collaborations to improve protocols and models to lead to reproducible,
      interpretable, high-quality preclinical data. This approach will certainly
      increase our chance to 1 day offer stem cell therapeutic options for patients
      with all-too-common renal diseases.

PMID- 30302938
TI  - Concise Review: The Current State of Human in vitro Cardiac Disease Modeling: A
      Focus on Gene Editing and Tissue Engineering.
AB  - Until recently, in vivo and ex vivo experiments were the only means to determine
      factors and pathways involved in disease pathophysiology. After the generation of
      characterized human embryonic stem cell lines, human diseases could readily be
      studied in an extensively controllable setting. The introduction of human-induced
      pluripotent stem cells, a decade ago, allowed the investigation of hereditary
      diseases in vitro. In the field of cardiology, diseases linked to known genes
      have successfully been studied, revealing novel disease mechanisms. The direct
      effects of various mutations leading to hypertrophic cardiomyopathy, dilated
      cardiomyopathy, arrythmogenic cardiomyopathy, or left ventricular noncompaction
      cardiomyopathy are discovered as a result of in vitro disease modeling.
      Researchers are currently applying more advanced techniques to unravel more
      complex phenotypes, resulting in state-of-the-art models that better mimic in
      vivo physiology. The continued improvement of tissue engineering techniques and
      new insights into epigenetics resulted in more reliable and feasible platforms
      for disease modeling and the development of novel therapeutic strategies. The
      introduction of CRISPR-Cas9 gene editing granted the ability to model diseases in
      vitro independent of induced pluripotent stem cells. In addition to highlighting
      recent developments in the field of human in vitro cardiomyopathy modeling, this
      review also aims to emphasize limitations that remain to be addressed; including
      residual somatic epigenetic signatures induced pluripotent stem cells, and
      modeling diseases with unknown genetic causes. Stem Cells Translational Medicine
      2018.

PMID- 30302939
TI  - Different Effects of Pro-Inflammatory Factors and Hyperosmotic Stress on Corneal
      Epithelial Stem/Progenitor Cells and Wound Healing in Mice.
AB  - Chronic inflammation and severe dry eye are two important adverse factors for the
      successful transplant of cultured limbal stem cells. The aim of this study was to
      investigate the effects of inflammation and hyperosmotic stress (a key
      pathological factor in dry eye) on corneal epithelial stem cells (CESCs) and
      corneal epithelial wound healing. We observed that the CESCs exhibited
      significant morphological changes when treated with interleukin-1 beta (IL
      1beta), tumor necrosis factor alpha (TNF-alpha), or hyperosmotic stress. Colony
      forming efficiency or colony-forming size was decreased with the increasing
      concentrations of IL-1beta, TNF-alpha, or hyperosmotic stress, which was
      exacerbated when treated simultaneously with pro-inflammatory factors and
      hyperosmotic stress. However, the colony-forming capacity of CESCs recovered more
      easily from pro-inflammatory factor treatment than from hyperosmotic stress
      treatment. Moreover, when compared with pro-inflammatory factors treatment,
      hyperosmotic stress treatment caused a more significant increase of apoptotic and
      necrotic cell numbers and cell cycle arrest in the G2/M phase. Furthermore, the
      normal ability of corneal epithelial wound healing in the mice model was
      suppressed by both pro-inflammatory factors and hyperosmotic stress treatment,
      and especially severely by hyperosmotic stress treatment. In addition,
      inflammation combined with hyperosmotic stress treatment induced more serious
      epithelial repair delays and apoptosis in corneal epithelium. Elevated levels of
      inflammatory factors were found in hyperosmotic stress-treated cells and mice
      corneas, which persisted even during the recovery period. The results suggested
      that pro-inflammatory factors cause transient inhibition, while hyperosmotic
      stress causes severe apoptosis and necrosis, persistent cell cycle arrest of
      CESCs, and severe corneal wound healing delay. Stem Cells Translational Medicine
      2018.

PMID- 30302940
TI  - Pre-hospital administration of ticagrelor in diabetic patients with ST-elevation
      myocardial infarction undergoing primary angioplasty: A sub-analysis of the
      ATLANTIC trial.
AB  - OBJECTIVE: We investigated, in the contemporary era of ST-elevation myocardial
      infarction (STEMI) treatment, the influence of diabetes mellitus (DM) on
      cardiovascular outcomes, and whether pre-hospital administration of ticagrelor
      may affect these outcomes in a subgroup of STEMI patients with DM. BACKGROUND: DM
      patients have high platelet reactivity and a prothrombotic condition which
      highlight the importance of an effective antithrombotic regimen in this high-risk
      population. METHODS: In toal 1,630 STEMI patients enrolled in the ATLANTIC trial
      who underwent primary percutaneous coronary intervention (PCI) were included.
      Multivariate analysis was used to explore the association of DM with outcomes and
      potential treatment-by-diabetes interaction was tested. RESULTS: A total of
      214/1,630 (13.1%) patients had DM. DM was an independent predictor of poor
      myocardial reperfusion as reflected by less frequent ST-segment elevation
      resolution (>=70%) after PCI (OR 0.59, 95% CI 0.43-0.82, P < 0.01) and was an
      independent predictor of the composite 30-day outcomes of death/new myocardial
      infarction (MI)/urgent revascularization/definite stent thrombosis (ST) (OR 2.80,
      95% CI 1.62-4.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08
      5.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54-28.22, P < 0.01). No
      significant interaction between pre-hospital ticagrelor vs in-hospital ticagrelor
      administration and DM was present for the clinical, electrocardiographic and
      angiographic outcomes as well as for thrombolysis in myocardial infarction major
      bleeding. CONCLUSIONS: DM remains independently associated with poor myocardial
      reperfusion and worse 30-day clinical outcomes. No significant interaction was
      found between pre-hospital vs in-hospital ticagrelor administration and DM
      status. Further approaches for the treatment of DM patients are needed. CLINICAL
      TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580.

PMID- 30302941
TI  - Energy Transfer-Assisted Whispering Gallery Mode Lasing in Conjugated
      Polymer/Europium Hybrid Microsphere Resonators.
AB  - Lanthanide metal complexes display luminescence with narrow bandwidth. Here, we
      present coupling of the luminescence from europium ion (Eu3+ ) with whispering
      gallery modes (WGMs) in conjugated polymer microsphere resonators. Self-assembly
      of fluorene-terpyridine alternating copolymer, coordinated by Eu3+ (F8tpy-Eu3+ ),
      forms well-defined microspheres with an average diameter of 3.2 MUm. Upon focused
      laser excitation, a microsphere of F8tpy copolymer displays WGM photoluminescence
      (PL) at a wide spectral range from 420 to 680 nm. In contrast, F8tpy-Eu3+ hybrid
      microspheres exhibit sharp WGM PL at a narrow spectral range of 615-630 nm, which
      is characteristic of luminescence from Eu3+ . The PL behavior indicates that
      photoinduced energy transfer from F8tpy to Eu3+ occurs efficiently. Furthermore,
      the intensity of the PL peak increases nonlinearly upon strong pumping,
      indicating that a lasing action appears with the threshold of 1.85 mJ cm-2 .
      These results will pave the way for developing microlasers and photonic devices
      from soft organic materials.

PMID- 30302942
TI  - Arabidopsis BIG1 and BIG5 are crucial for male gametophyte transmission.
AB  - Arabidopsis contains five Brefeldin A-inhibited guanine nucleotide exchange
      factors (BIGs), which play a critical role in vesicle biogenesis for protein
      traffic from the Golgi to the plasma membrane. Biological processes regulated by
      BIG1-BIG4 are postulated to be distinct from those by BIG5. However, we show that
      the self-pollinated BIG1+/- big5 silique do not produce homozygous seeds, and
      some pollen tubes from BIG1+/- big5 anthers grew slowly in vitro and failed to
      target nearby ovules in vivo. We identified the big1 big5 homozygote from the
      progeny of BIG1+/- big5 plants transformed with BIG5, whose expression is driven
      by a pollen-specific promoter pLat52, indicating that male gametophyte
      transmission is blocked in the double mutant. Confocal microscopy indicated that
      BIG1 and BIG5 are co-localized in the Golgi network. Thus, our data indicate that
      BIG1 and BIG5 are crucial for male gametophyte transmission.

PMID- 30302943
TI  - Classification of Established Atopic Dermatitis in Children with the In Vivo
      Imaging Methods.
AB  - Atopic dermatitis (AD) is a cutaneous disease resulting from a defective barrier
      and dysregulated immune response. The severity scoring of atopic dermatitis
      (SCORAD) is used to classify AD. Noninvasive imaging approaches supplementary to
      SCORAD were investigated. Cr:forsterite laser-based microscopy was employed to
      analyze endogenous third-harmonic generation (THG) and second-harmonic generation
      (SHG) signals from skin. Imaging parameters were compared between different AD
      severities. 3D reconstruction of imaged skin layers were performed. Finally,
      statistic models from quantitative imaging parameters were developed for
      predicting disease severity. Our data demonstrate that THG signal intensity of
      lesional skin in AD were significantly increased and was positively correlated
      with AD severity. Characteristic GLCM values were observed in more severe AD. In
      the 3D reconstruction video, individual dermal papilla and obvious fibrosis in
      the upper papillary dermis were easily identified. Our estimation models could
      predict the disease severity of AD patients with an accuracy of nearly 85%. The
      THG signal intensity and characteristic GLCM patterns are associated with AD
      severity and can serve as quantitative predictive parameters. Our imaging
      approach can be used to identify the histopathological changes of AD objectively,
      and to complement the SCORAD index, thus improving the accuracy of classifying AD
      severity. This article is protected by copyright. All rights reserved.

PMID- 30302945
TI  - Chronic non-malignant pain: it's complicated.

PMID- 30302944
TI  - Women's perceptions of body mass index.
AB  - Women may not have an accurate perception of their own body weight and vary in
      understanding about healthy weight. The study's aim was to assess women's
      accuracy of their own body mass index (BMI), understanding of the healthiest body
      weight and opinion of the most attractive body figure. We surveyed 385 women
      (age, 19-77 years) attending our obstetrics and gynaecology clinics with an
      anonymous survey demonstrating a selection of Body Image Scale graphics to
      represent their current body, the healthiest body and the most attractive body.
      There was a significant positive correlation between Body Image Scale graphic
      selected and BMI (r = 0.80; P < 0.0001). The selected Body Image Scale graphic
      was accurate or within 1 graphic higher or lower than BMI in 88% of participants.
      The mean BMI of women accurately selecting the appropriate graphic (BMI, 29 +/- 8
      kg m-2 ) was significantly lower than that of women selecting the graphic lower
      than their BMI (BMI, 37 +/- 7 kg m-2 ) but was significantly higher than those
      selecting a graphic higher than their BMI (BMI, 25 +/- 4 kg m-2 ). For healthiest
      figure, 58% women selected a graphic representing overweight BMI and 2% women
      selected a graphic with Class 1 obesity. For most attractive figure, 48% women
      selected a graphic representing normal BMI, 49% women selected a graphic
      representing overweight BMI and 1% of women selected a graphic with Class 1
      obesity. It is important to provide counselling about ideal weight, healthy
      lifestyle choices and consequences of obesity.

PMID- 30302947
TI  - Social jetlag, sleep-related parameters, and glycemic control in adults with type
      1 diabetes: Results of a cross-sectional study.
AB  - BACKGROUND: Social jetlag (SJL) is a small recurrent circadian rhythm disruption
      and the most frequent form of circadian rhythm misalignment. The main aim of this
      study was to investigate the effect of SJL on glycemic control, as assessed by
      HbA1c, in real-life settings. METHODS: In all, 115 consecutive patients with type
      1 diabetes (T1D) were analyzed cross-sectionally. Data on bedtime, sleep onset
      latency, and wake up time on weekdays and weekends during the previous month were
      collected from all participants and used to calculate SJL, chronotype, and sleep
      duration. Sleep quality was assessed by the Pittsburgh Sleep Quality Index
      (PSQI). A PSQI score > 5 was considered as an indicator of poor sleep quality.
      RESULTS: Patients with SJL >= 1 hour had significantly higher adjusted values of
      HbA1c than those with SJL <1 hour (8.7% vs 8.0%; P = 0.029). In unadjusted
      multivariate regression analysis, SJL >= 1 hour and poor sleep quality were
      significant predictors of HbA1c values, explaining 22.7% and 23.5%, respectively,
      of the increase in HbA1c. After adjusting for age, sex, diabetes duration,
      insulin dose (kg/d), insulin regimen and body mass index, only SJL >= 1 hour
      remained associated with HbA1c (beta = 0.253; P = 0.026). There was no
      significant interaction between SJL >= 1 hour and poor sleep quality in either
      the unadjusted or adjusted models (Pinteraction  = 0.914). CONCLUSIONS: In
      patients with T1D, SJL is associated with poor glycemic control, acting
      independently of sleep quality, sleep duration, and chronotype to exert a
      deleterious effect on glycemic control.

PMID- 30302946
TI  - The role of tissue and serum carcinoembryonic antigen in stages I to III of
      colorectal cancer-A retrospective cohort study.
AB  - PURPOSE: Tissue carcinoembryonic antigen (t-CEA) and serum carcinoembryonic
      antigen (s-CEA) expression profiles are the most useful tumor markers for the
      diagnosis and evaluation of colorectal cancer (CRC) worldwide; however, their
      roles in CRC progression remain controversial. This study aimed to compare the
      prognostic values of both s-CEA and t-CEA in CRC. METHODS: A total of 517
      patients from January 2006 to December 2010 with stages I-III CRC were
      retrospectively examined, with 5-year postoperative follow-up and death as end
      points. T-CEA expression, s-CEA expression, and clinical pathological parameters
      were inputted into the SPSS 21.0 software. The Kaplan-Meier method was used to
      analyze the 5-year disease-free survival (DFS) rate of patients in different
      tumor node metastasis (TNM) stages based on t-CEA and s-CEA expression. RESULTS:
      Tumor differentiation and the number of positive lymph node harvests were
      significantly different among the t-CEA groups (P < 0.001, P = 0.002); however,
      clinicopathological features showed no significant difference. The groups with
      high s-CEA and t-CEA expression had a significantly poorer prognosis than those
      with low s-CEA (P = 0.021) and t-CEA (P < 0.01) expression, respectively. The
      multivariate analysis demonstrated that t-CEA was an independent prognostic
      factor in CRC (P < 0.001), but s-CEA was not (P = 0.339). The 5-year disease-free
      survival rates among the t-CEA groups were significantly different in stages I,
      II, and III of CRC (P = 0.001, P < 0.001, P < 0.001), whereas in the s-CEA
      groups, this difference was observed only in stage III (P = 0.014). CONCLUSION:
      This study shows that postoperative t-CEA expression is an independent factor
      associated with poorer CRC prognosis and has a higher prognostic value than that
      of preoperative s-CEA expression.

PMID- 30302948
TI  - Genetic inactivation of ZCCHC6 suppresses IL-6 expression and reduces the
      severity of experimental osteoarthritis in mice.
AB  - OBJECTIVE: Cytokine expression is tightly regulated post-transcriptionally but
      high levels of IL-6 in osteoarthritis (OA) indicate disruption of regulatory
      mechanisms. ZCCHC6 enzyme is implicated in post-transcriptional regulation of
      inflammatory cytokine expression but its role in OA pathogenesis is unknown. Here
      we studied whether ZCCHC6 directs the expression of IL-6 and influence OA
      pathogenesis in vivo. METHODS: Human and mouse chondrocytes were stimulated with
      recombinant IL-1beta. We knocked down the expression of ZCCHC6 in human
      chondrocytes by siRNAs. IL-6 transcript stability was determined by Actinomycin-D
      chase and 3'-uridylation of miRNAs was determined by deep sequencing. Zcchc6-/-
      mice were produced by gene targeting. OA was surgically induced in the knee
      joints of mice and the disease severity was scored using a semi-quantitative
      scoring system. RESULTS: ZCCHC6 was markedly upregulated in the damaged cartilage
      from human OA patients and from wild type mice with surgically-induced OA.
      Overexpression of ZCCHC6 induced the expression of IL-6 and its knockdown reduced
      the IL-6 transcript stability and IL-1beta-induced expression in chondrocytes.
      Reintroduction of Zcchc6 in Zcchc6-/- chondrocytes rescued the IL-1beta-induced
      IL-6 expression. Knockdown of ZCCHC6 reduced the population of miR-26b with 3'
      uridylation by 60%. Zcchc6-/- mice with surgically-induced OA produced low levels
      of IL-6 and showed reduced cartilage damage and synovitis in the joints.
      CONCLUSIONS: ZCCHC6 enhance IL-6 expression in chondrocytes through transcript
      stabilization and by uridylating miR-26b which abrogates repression of IL-6.
      Inhibition of IL-6 expression and significantly reduced OA severity in Zcchc6-/-
      mice identify ZCCHC6 as a novel therapeutic target to inhibit disease
      pathogenesis. This article is protected by copyright. All rights reserved.

PMID- 30302949
TI  - Improvement of radiographer commenting accuracy of the appendicular skeleton
      following a short course in plain radiography image interpretation: A pilot
      study.
AB  - INTRODUCTION: Radiographers are at times required to provide preliminary
      information on plain radiography when significant findings are identified. The
      aim of the study was to evaluate the effectiveness of two short training modules
      to improve the accuracy of image interpretation of the appendicular skeleton
      amongst a group of radiographers. METHODS: Eight radiographers volunteered to
      participate in the study. All undertook a pre-test and, following delivery of
      course materials, an immediate post-test for two consecutive modules. A retention
      test was undertaken 6 months later. Sensitivity (Sn), specificity (Sp) and
      accuracy (Acc) scores were evaluated against the "Gold Standard" radiologists'
      reports. Paired-samples t-tests were carried out to compare image interpretation
      scores between the start of module one to the end of module two, and between the
      end of module 2 and 6 months later. Summary receiver operating characteristics
      (SROC) scores on each of the participants' module two post-test study results
      were undertaken. RESULTS: Significant improvements in scores were achieved
      between the mean (SD) scores of module 1 pre-test (77.5 (+/-3.9)) and the module
      2 post-test (83.6 (+/-3.2) (P =0.022)). Sn, Sp and Acc scores increased from the
      start of module 1 pre-test to the end of module 2 post-test (Sn: 82.28-86.25%;
      Sp: 75.29-84.66%; Acc: 81.68-85.97%). The retention test revealed a non
      significant reduction in mean scores (80.0 (+/-5.1)) when compared to post-test
      module 2 (83.6 (+/-3.2) (P =0.184)). SROC revealed an area under the curve of
      0.90. CONCLUSION: Participants achieved significant improvements in commenting
      accuracy on plain radiography of the appendicular skeleton after completion of
      the two modules. However, continuous application and ongoing professional
      development is essential in order to maintain and develop the skills acquired.

PMID- 30302950
TI  - Supramolecular Nanofibers of Drug-Peptide Amphiphile and Affibody Suppress HER2+
      Tumor Growth.
AB  - Antibody-based medicines and nanomedicines are very promising for cancer therapy
      due to the high specificity and efficacy of antibodies. However, antibody-drug
      conjugates and antibody-modified nanomaterials frequently suffer from low drug
      loading and loss of functions due to the covalent modification of the antibody. A
      novel and versatile strategy to prepare supramolecular nanomaterials by the
      coassembly of an affibody (antiHER2) and drug-peptide amphiphiles is reported
      here. During the enzyme-instructed self-assembly process, the drug-peptide
      amphiphile can coassemble with the affibody, resulting in supramolecular
      nanofibers in hydrogels. The drug loading in the supramolecular nanofibers is
      high (>30 wt%), and the stability of antiHER2 is significantly improved in the
      nanofibers at 37  degrees C (>15 d in vitro). The supramolecular nanofibers
      exhibit high affinity for HER2+ cancer cells and can be efficiently taken up by
      these cells. In a mouse tumor model, the supramolecular nanofibers abolish HER2+
      NCI-N87 tumor growth due to the good accumulation and retention of nanofibers in
      tumor. This study provides a novel strategy to prepare nanomedicines with high
      drug loading and high specificity.

PMID- 30302951
TI  - Dilemma of Asthma Treatment in Mild Patients.
AB  - Inhaled corticosteroids (ICSs) have been widely used as a key medication for
      asthma control. However, ICSs have been known to cause respiratory infections,
      such as pneumonia and pulmonary tuberculosis. Consequently, a dilemma exists
      regarding recommendation of persistent lifetime use of ICSs to mild asthma
      patients. Short-acting beta-agonists (SABAs) have also been widely used for
      symptom relief. However, SABAs have been reported to increase the risk of asthma
      related death, though incidences have been very rare. Consequently, a dilemma
      exists regarding recommendation of a SABA alone without an ICS or a controller to
      asthma patients even with very mild disease. In the real world, asthma patients
      tend to intermittently use ICS and more likely to be dependent on SABA since many
      patients want immediate relief of their symptoms. Consequently, a dilemma exists
      regarding the underuse of ICSs but the overuse of SABAs. One strategy for solving
      the presented dilemma would be identification of patients with asthma who require
      persistent use of asthma controllers. Such patients, who may be referred to as
      "persistent controller users," should continuously receive ICSs, even under
      controlled states of asthma. Another strategy would be a patient-adjusted,
      symptom-driven, intermittent-to-regular treatment combining low-dose ICS/rapid
      onset long-acting beta-agonists instead of using a SABA alone or with low-dose
      ICS for the asthma patients with mild disease. Both of these two strategies could
      avoid the risky treatment of a SABA alone without an ICS and could reduce the
      dose of ICS with the maintenance of asthma control.

PMID- 30302952
TI  - The Development of the Korean Lung Cancer Registry (KALC-R).
AB  - Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer
      related deaths worldwide. Globally, there were an estimated 1.8 million new cases
      and 1.59 million deaths in 2012. In Korea, the incidence of lung cancer is
      increasing and 24,267 (47.6/100,000) patients with lung cancer were registered at
      the Korea Central Cancer Registry in 2015. Previous nationwide surveys of lung
      cancer were performed in 1998 by the Korean Academy of Tuberculosis and
      Respiratory Diseases and in 2007 by the Korean Association for Lung Cancer
      (KALC), but the studies faced difficulties in maintaining lung cancer registry
      because of limitations regarding the Private Information Protection Act. To
      produce unbiased and reliable epidemiological data, the KALC and Korean Central
      Cancer Registry developed a detailed lung cancer registry (KALC-R) data
      structure. Following a pilot survey of 489 lung cancer cases in 2013, about 10%
      of the sampled lung cancer cases from the Korean Central Cancer Registry are
      surveyed each year. With the analysis of detailed data from the KALC-R, an
      important epidemiological background for scientific research or policy
      development is expected to be generated.

PMID- 30302953
TI  - Infection Source and Epidemiology of Nontuberculous Mycobacterial Lung Disease.
AB  - Nontuberculous mycobacteria (NTM) are ubiquitous organisms that are generally
      found not only in the natural environment but also in the human engineered
      environment, including water, soil, and dust. These organisms can form biofilms
      and can be readily aerosolized because they are hydrophobic owing to the presence
      of the lipid-rich outer membrane. Aerosolization and subsequent inhalation were
      the major route of NTM lung disease. Water distribution systems and household
      plumbing are ideal habit for NTM and the main transmission route from natural
      water to household. NTM have been isolated from drinking water, faucets,
      pipelines, and water tanks. Studies that used genotyping have shown that NTM
      isolates from patients are identical to those in the environment, that is, from
      shower water, showerheads, tap water, and gardening soil. Humans are likely to be
      exposed to NTM in their homes through simple and daily activities, such as
      drinking, showering, or gardening. In addition to environmental factors, host
      factors play an important role in the development of NTM lung disease. The
      incidence and prevalence of NTM lung disease are increasing worldwide, and this
      disease is rapidly becoming a major public health problem. NTM lung disease is
      associated with substantially impaired quality of life, increased morbidity and
      mortality, and high medical costs. A more comprehensive understanding of the
      infection source and epidemiology of NTM is essential for the development of new
      strategies that can prevent and control NTM infection.

PMID- 30302954
TI  - Sepsis: Early Recognition and Optimized Treatment.
AB  - Sepsis is a life-threatening condition caused by infection and represents a
      substantial global health burden. Recent epidemiological studies showed that
      sepsis mortality rates have decreased, but that the incidence has continued to
      increase. Although a mortality benefit from early-goal directed therapy (EGDT) in
      patients with severe sepsis or septic shock was reported in 2001, three
      subsequent multicenter randomized studies showed no benefits of EGDT versus usual
      care. Nonetheless, the early administration of antibiotics and intravenous fluids
      is considered crucial for the treatment of sepsis. In 2016, new sepsis
      definitions (Sepsis-3) were issued, in which organ failure was emphasized and use
      of the terms "systemic inflammatory response syndrome" and "severe sepsis" was
      discouraged. However, early detection of sepsis with timely, appropriate
      interventions increases the likelihood of survival for patients with sepsis.
      Also, performance improvement programs have been associated with a significant
      increase in compliance with the sepsis bundles and a reduction in mortality. To
      improve sepsis management and reduce its burden, in 2017, the World Health
      Assembly and World Health Organization adopted a resolution that urged
      governments and healthcare workers to implement appropriate measures to address
      sepsis. Sepsis should be considered a medical emergency, and increasing the level
      of awareness of sepsis is essential.

PMID- 30302955
TI  - Potential Therapeutic Strategy in Chronic Obstructive Pulmonary Disease Using
      Pioglitazone-Augmented Wharton's Jelly-Derived Mesenchymal Stem Cells.
AB  - BACKGROUND: A recent study reported that mesenchymal stem cells possess potential
      cellular therapeutic properties for treating patients with chronic obstructive
      pulmonary disease, which is characterized by emphysema. We examined the potential
      therapeutic effect of Wharton's Jelly-derived mesenchymal stem cells (WJMSCs),
      following pretreatment with pioglitazone, in lung regeneration mouse emphysema
      models. METHODS: We used two mouse emphysema models, an elastase-induced model
      and a cigarette smoke-induced model. We intravenously injected WJMSCs
      (1*104/mouse) to mice, pretreated or not, with pioglitazone for 7 days. We
      measured the emphysema severity by mean linear intercepts (MLI) analysis using
      lung histology. RESULTS: Pioglitazone pretreated WJMSCs (pioWJMSCs) were
      associated with greater lung regeneration than non-augmented WJMSCs in the two
      mouse emphysema models. In the elastase-induced emphysema model, the MLIs were
      59.02+/-2.42 MUm (n=6), 72.80+/-2.87 MUm (n=6), for pioWJMSCs injected mice, and
      non-augmented WJMSCs injected mice, respectively (p<0.01). Both pioWJMSCs and non
      augmented WJMSCs showed regenerative effects in the cigarette smoke emphysema
      model (MLIs were 41.25+/-0.98 [n=6] for WJMSCs and38.97+/-0.61 MUm [n=6] for
      pioWJMSCs) compared to smoking control mice (51.65+/-1.36 MUm, n=6). The mean
      improvement of MLI appeared numerically better in pioWJMSCs than in non-augmented
      WJMSCs injected mice, but the difference did not reach the level of statistical
      significance (p=0.071). CONCLUSION: PioWJMSCs may produce greater lung
      regeneration, compared to non-augmented WJMSCs, in a mouse emphysema model.

PMID- 30302956
TI  - Correlation between GenoType MTBDRplus Assay and Phenotypic Susceptibility Test
      for Prothionamide in Patients with Genotypic Isoniazid Resistance.
AB  - BACKGROUND: The purpose of this study was to analyze the relationship between the
      gene mutation patterns by the GenoType MTBDRplus (MTBDRplus) assay and the
      phenotypic drug susceptibility test (pDST) results of isoniazid (INH) and
      prothionamide (Pto). METHODS: A total of 206 patients whose MTBDRplus assay
      results revealed katG or inhA mutations were enrolled in the study. The pDST
      results were compared to mutation patterns on the MTBDRplus assay. RESULTS: The
      katG and inhA mutations were identified in 68.0% and 35.0% of patients,
      respectively. Among the 134 isolated katG mutations, three (2.2%), 127 (94.8%)
      and 11 (8.2%) were phenotypically resistant to low-level INH, high-level INH, and
      Pto, respectively. Among the 66 isolated inhA mutations, 34 (51.5%), 18 (27.3%)
      and 21 (31.8%) were phenotypically resistant to low-level INH, high-level INH,
      and Pto, respectively. Of the 34 phenotypic Pto resistant isolates, 21 (61.8%),
      11 (32.4%), and two (5.9%) had inhA, katG, and both gene mutations. CONCLUSION:
      It is noted that Pto may still be selected as one of the appropriate multidrug
      resistant tuberculosis regimen, although inhA mutation is detected by the
      MTBDRplus assay until pDST confirms a Pto resistance. The reporting of detailed
      mutation patterns of the MTBDRplus assay may be important for clinical practice,
      rather than simply presenting resistance or susceptibility test results.

PMID- 30302957
TI  - Pre-immigration Screening for Tuberculosis in South Korea: A Comparison of Smear-
      and Culture-Based Protocols.
AB  - BACKGROUND: Tuberculosis (TB) is the most important disease screened for upon
      patient history review during preimmigration medical examinations as performed in
      South Korea in prospective immigrants to certain Western countries. In 2007, the
      U.S. Centers for Disease Control and Prevention (CDC) changed the TB screening
      protocol from a smear-based test to the complete Culture and Directly Observed
      Therapy Tuberculosis Technical Instructions (CDOT TB TI) for reducing the
      incidence of TB in foreign-born immigrants. METHODS: This study evaluated the
      effect of the revised (as compared with the old) protocol in South Korea.
      RESULTS: Of the 40,558 visa applicants, 365 exhibited chest radiographic results
      suggestive of active or inactive TB, and 351 underwent sputum tests (acid-fast
      bacilli smear and Mycobacterium tuberculosis culture). To this end, using the
      CDOT TB TI, 36 subjects (88.8 per 105 of the population) were found to have TB,
      compared with only seven using the older U.S. CDC technical instruction (TI)
      (p<0.001). In addition, there were six drug-resistant cases which were identified
      (16.7 per 105 of the population), two of whom had multidrug-resistance (5.6 per
      105 of the population). CONCLUSION: The culture-based 2007 TI identified a great
      deal of TB cases current to the individuals tested, as compared to older U.S. CDC
      TI.

PMID- 30302958
TI  - Direct and Indirect Costs of Chronic Obstructive Pulmonary Disease in Korea.
AB  - BACKGROUND: Understanding the burden of disease is important to establish cost
      effective treatment strategies and to allocate healthcare resources
      appropriately. However, little reliable information is available regarding the
      overall economic burden imposed by chronic obstructive pulmonary disease (COPD)
      in Korea. METHODS: This study is a multicenter observational research on the COPD
      burden in Korea. Total COPD costs were comprised of three categories: direct
      medical, direct non-medical, and indirect costs. For direct medical costs,
      institutional investigation was performed at 13 medical facilities mainly based
      on the claims data. For direct non-medical and indirect costs, site-based surveys
      were administered to the COPD patients during routine visits. Total costs were
      estimated using the COPD population defined in the recent report. RESULTS: The
      estimated total costs were approximately 1,245 million US dollar (1,408 billion
      Korean won). Direct medical costs comprised approximately 20% of the total
      estimated costs. Of these, formal medical costs held more than 80%. As direct non
      medical costs, nursing costs made up the largest percentage (39%) of the total
      estimated costs. Costs for COPD-related loss of productivity formed four fifths
      of indirect costs, and accounted for up to 33% of the total costs. CONCLUSION:
      This study shows for the first time the direct and indirect costs of COPD in
      Korea. The total costs were enormous, and the costs of nursing and lost
      productivity comprised approximately 70% of total costs. The results provide
      insight for an effective allocation of healthcare resources and to inform
      establishment of strategies to reduce national burden of COPD.

PMID- 30302959
TI  - Identification of Serial DNA Methylation Changes in the Blood Samples of Patients
      with Lung Cancer.
AB  - BACKGROUND: The development of lung cancer results from the interaction between
      genetic mutations and dynamic epigenetic alterations, although the exact
      mechanisms are not completely understood. Changes in DNA methylation may be a
      promising biomarker for early detection and prognosis of lung cancer. We
      evaluated the serial changes in genome-wide DNA methylation patterns in blood
      samples of lung cancer patients. METHODS: Blood samples were obtained for three
      consecutive years from three patients (2 years before, 1 year before, and after
      lung cancer detection) and from three control subjects (without lung cancer). We
      used the MethylationEPIC BeadChip method, which covers the 850,000 bp cytosine
      phosphate-guanine (CpG) site, to conduct an epigenome-wide analysis. Significant
      differentially methylated regions (DMRs) were identified using p-values <0.05 in
      a correlation test identifying serial methylation changes and serial increase or
      decrease in beta value above 0.1 for three consecutive years. RESULTS: We found
      three significant CpG sites with differentially methylated beta values and 7,105
      CpG sites with significant correlation from control patients without lung cancer.
      However, there were no significant DMRs. In contrast, we found 11 significant CpG
      sites with differentially methylated beta values and 10,562 CpG sites with
      significant correlation from patients with lung cancer. There were two
      significant DMRs: cg21126229 (RNF212) and cg27098574 (BCAR1). CONCLUSION: This
      study revealed DNA methylation changes that might be implicated in lung cancer
      development. The DNA methylation changes may be the possible candidate target
      regions for the early detection and prevention of lung cancer.

PMID- 30302960
TI  - High Proportion of Adult Cases and Prevalence of Metabolic Syndrome in Type 1
      Diabetes Mellitus Population in Korea: A Nationwide Study.
AB  - BACKGROUND: The prevalence and incidence of type 1 diabetes mellitus (T1DM) in
      all age groups and the prevalence of metabolic syndrome in patients with T1DM in
      Korea were estimated. METHODS: The incidence and prevalence of T1DM between 2007
      and 2013 were calculated using the Korean National Health Insurance Service
      (NHIS) datasets of claims. Clinical characteristics and prevalence of metabolic
      syndrome in individuals with T1DM between 2009 and 2013 were determined using the
      database of NHIS preventive health checkups. RESULTS: The prevalence of T1DM in
      Korea between 2007 and 2013 was 0.041% to 0.047%. The annual incidence rate of
      T1DM in Korea in 2007 to 2013 was 2.73 to 5.02/100,000 people. Although the
      incidence rate of typical T1DM was highest in teenagers, it remained steady in
      adults over 30 years of age. In contrast, the incidence rate of atypical T1DM in
      2013 was higher in people aged 40 years or older than in younger age groups. Age-
      and sex-adjusted prevalence of metabolic syndrome in patients with T1DM was
      51.65% to 55.06% between 2009 and 2013. CONCLUSION: T1DM may be more common in
      Korean adults than previously believed. Metabolic syndrome may be a frequent
      finding in individuals with T1DM in Korea.

PMID- 30302961
TI  - Association of Thigh Muscle Mass with Insulin Resistance and Incident Type 2
      Diabetes Mellitus in Japanese Americans.
AB  - BACKGROUND: Skeletal muscle plays a major role in glucose metabolism. We
      investigated the association between thigh muscle mass, insulin resistance, and
      incident type 2 diabetes mellitus (T2DM) risk. In addition, we examined the role
      of body mass index (BMI) as a potential effect modifier in this association.
      METHODS: This prospective study included 399 Japanese Americans without diabetes
      (mean age 51.6 years) who at baseline had an estimation of thigh muscle mass by
      computed tomography and at baseline and after 10 years of follow-up a 75-g oral
      glucose tolerance test and determination of homeostasis model assessment of
      insulin resistance (HOMA-IR). We fit regression models to examine the association
      between thigh muscle area and incidence of T2DM and change in HOMA-IR, both
      measured over 10 years. RESULTS: Thigh muscle area was inversely associated with
      future HOMA-IR after adjustment for age, sex, BMI, HOMA-IR, fasting plasma
      glucose, total abdominal fat area, and thigh subcutaneous fat area at baseline
      (P=0.033). The 10-year cumulative incidence of T2DM was 22.1%. A statistically
      significant interaction between thigh muscle area and BMI was observed, i.e.,
      greater thigh muscle area was associated with lower risk of incident T2DM for
      subjects at lower levels of BMI, but this association diminished at higher BMI
      levels. CONCLUSION: Thigh muscle mass area was inversely associated with future
      insulin resistance. Greater thigh muscle area predicts a lower risk of incident
      T2DM for leaner Japanese Americans.

PMID- 30302962
TI  - Utility of Serum Albumin for Predicting Incident Metabolic Syndrome according to
      Hyperuricemia.
AB  - BACKGROUND: Serum albumin and uric acid have been positively linked to metabolic
      syndrome (MetS). However, the association of MetS incidence with the combination
      of uric acid and albumin levels has not been investigated. We explored the
      association of albumin and uric acid with the risk of incident MetS in
      populations divided according to the levels of these two parameters. METHODS: In
      this retrospective longitudinal study, 11,613 non-MetS participants were enrolled
      among 24,185 individuals who had undergone at least four annual check-ups between
      2006 and 2012. The risk of incident MetS was analyzed according to four groups
      categorized by the sex-specific medians of serum albumin and uric acid. RESULTS:
      During 55,407 person-years of follow-up, 2,439 cases of MetS developed. The risk
      of incident MetS increased as the uric acid category advanced in individuals with
      lower or higher serum albumin categories with hazard ratios (HRs) of 1.386 (95%
      confidence interval [CI], 1.236 to 1.554) or 1.314 (95% CI, 1.167 to 1.480).
      However, the incidence of MetS increased with higher albumin levels only in
      participants in the lower uric acid category with a HR of 1.143 (95% CI, 1.010 to
      1.294). CONCLUSION: Higher levels of albumin were associated with an increased
      risk of incident MetS only in individuals with lower uric acid whereas higher
      levels of uric acid were positively linked to risk of incident MetS regardless of
      albumin level.

PMID- 30302963
TI  - Proportion and Characteristics of the Subjects with Low Muscle Mass and Abdominal
      Obesity among the Newly Diagnosed and Drug-Naive Type 2 Diabetes Mellitus
      Patients.
AB  - BACKGROUND: Sarcopenic obesity (SO) is a serious public health concern, few
      studies have examined the clinical implications of SO in newly-diagnosed type 2
      diabetes mellitus (T2DM) patients. We evaluated the prevalence of the newly
      diagnosed, drug-naive T2DM patients with low muscle mass with abdominal obesity
      and its association with insulin resistance and other diabetic complications.
      METHODS: We classified 233 drug-naive T2DM subjects into four groups according to
      abdominal obesity (waist circumference >=90 cm in men and >=85 cm in women) and
      low muscle mass status (appendicular skeletal muscle <7.0 kg/m2 for men and <5.4
      kg/m2 for women). RESULTS: The proportion of the subjects with low muscle mass
      and abdominal obesity among the newly diagnosed, drug-naive T2DM patients was
      8.2%. Homeostasis model assessment of insulin resistance (HOMA-IR) increased
      linearly according to body composition group from normal to abdominal obesity to
      both low muscle mass and abdominal obesity. The multiple logistic regression
      analysis indicated that subjects with low muscle mass and abdominal obesity (odds
      ratio [OR], 9.39; 95% confidence interval [CI], 2.41 to 36.56) showed a higher
      risk for insulin resistance, defined as HOMA-IR >=3, than those with abdominal
      obesity (OR, 5.36; 95% CI, 2.46 to 11.69), even after adjusting for other
      covariates. However, there were no differences in lipid profiles,
      microalbuminuria, or various surrogate markers for atherosclerosis among the four
      groups. CONCLUSION: Subjects with both low muscle mass and abdominal obesity had
      a higher risk of insulin resistance than those with low muscle mass or abdominal
      obesity only.

PMID- 30302964
TI  - Higher High Density Lipoprotein 2 (HDL2) to Total HDL Cholesterol Ratio Is
      Associated with a Lower Risk for Incident Hypertension.
AB  - BACKGROUND: Recent studies have suggested that high density lipoprotein (HDL)
      cholesterol is inversely associated with the development of hypertension. We
      aimed to determine the association between different HDL cholesterol subclasses
      and risk of future hypertension. METHODS: A total of 270 Japanese Americans (130
      men, 140 women) without hypertension between the ages of 34 to 75 years were
      enrolled. Blood pressure was measured with a mercury sphygmomanometer, and
      average blood pressure was calculated. Incident hypertension was determined 5 to
      6 and 10 to 11 years after enrollment. HDL2, HDL3, and total HDL cholesterol were
      measured at baseline. RESULTS: During 10 years of follow-up, the cumulative
      incidence of hypertension was 28.1% (76/270). In univariate analysis, age,
      diabetes, waist circumference, systolic and diastolic blood pressure, fasting
      glucose, insulin resistance index, total and low density lipoprotein cholesterol,
      and visceral adipose tissue were significant predictors for incident
      hypertension. Among the HDL cholesterol subclass, HDL2 cholesterol was inversely
      associated with hypertension incidence, but both total and HDL3 cholesterol were
      not. In addition, HDL2/HDL cholesterol was inversely associated with future
      hypertension risk. In multivariate analysis, age (odds ratio [OR], 1.71; 95%
      confidence interval [CI], 1.26 to 2.31; P=0.001), systolic blood pressure (OR,
      1.83; 95% CI, 1.31 to 2.56; P<0.001), and HDL2/HDL cholesterol (OR, 0.71; 95% CI,
      0.52 to 0.98; P=0.035), were associated with future development of hypertension.
      CONCLUSION: A higher proportion of HDL2 cholesterol among total HDL cholesterol
      predicted a lower risk for incident hypertension. However, concentrations of
      total HDL, HDL2, and HDL3 cholesterol were not independent predictors of incident
      hypertension.

PMID- 30302965
TI  - Cardiovascular Autonomic Neuropathy Predicts Higher HbA1c Variability in Subjects
      with Type 2 Diabetes Mellitus.
AB  - BACKGROUND: This study aimed to investigate the association between the presence
      and severity of cardiovascular autonomic neuropathy (CAN) and development of long
      term glucose fluctuation in subjects with type 2 diabetes mellitus. METHODS: In
      this retrospective cohort study, subjects with type 2 diabetes mellitus who
      received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4
      year of follow-up with >=6 measures of glycosylated hemoglobin (HbA1c) were
      included. The severity of CAN was categorized as normal, early, or severe CAN
      according to the CARTs score. HbA1c variability was measured as the standard
      deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c
      measurements. RESULTS: A total of 681 subjects were analyzed (294 normal, 318
      early, and 69 severe CAN). The HbA1c variability index values showed a positive
      relationship with the severity of CAN. Multivariable logistic regression analysis
      showed that CAN was significantly associated with the risk of developing higher
      HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes
      duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic
      retinopathy, coronary artery disease, insulin use, and antihypertensive
      medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12
      to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more
      prominent in subjects who had a longer duration of diabetes (>10 years) and lower
      mean HbA1c (<7%). CONCLUSION: CAN is an independent risk factor for future higher
      HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for
      stabilizing glucose fluctuation should be emphasized in subjects with CAN.

PMID- 30302966
TI  - Soluble Dipeptidyl Peptidase-4 Levels Are Associated with Decreased Renal
      Function in Patients with Type 2 Diabetes Mellitus.
AB  - BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) is strongly expressed in the kidney,
      and soluble levels of this protein are used as a marker in various chronic
      inflammatory diseases, including diabetes, coronary artery disease, and cancer.
      This study examined the association between the serum soluble DPP-4 levels and
      renal function or cardiovascular risk in patients with type 2 diabetes mellitus.
      METHODS: In this retrospective analysis, soluble DPP-4 levels were measured in
      preserved sera from 140 patients with type 2 diabetes mellitus who had
      participated in our previous coronary artery calcium (CAC) score study. RESULTS:
      The mean+/-standard deviation soluble DPP-4 levels in our study sample were 645+/
      152 ng/mL. Univariate analyses revealed significant correlations of soluble DPP-4
      levels with the total cholesterol (r=0.214, P=0.019) and serum creatinine levels
      (r=-0.315, P<0.001) and the estimated glomerular filtration rate (eGFR; estimated
      using the modification of diet in renal disease equation) (r=0.303, P=0.001). The
      associations of soluble DPP-4 levels with serum creatinine and GFR remained
      significant after adjusting for age, body mass index, and duration of diabetes.
      However, no associations were observed between soluble DPP-4 levels and the body
      mass index, waist circumference, or CAC score. CONCLUSION: These data suggest the
      potential use of serum soluble DPP-4 levels as a future biomarker of deteriorated
      renal function in patients with type 2 diabetes mellitus.

PMID- 30302967
TI  - Three-dimensional quantitative phase imaging of blood coagulation structures by
      optical projection tomography in flow cytometry using digital holographic
      microscopy.
AB  - Blood coagulation is an important role in the hemostasis process. In the
      observation using microscopies, an aggregation structure of red blood cells
      indicates the degree of blood coagulation. Recently, it has been proposed that
      digital holographic microscopy (DHM) is a powerful tool for biomedical cell
      imaging on the basis of quantitative phase information. DHM has the advantage in
      that the real-time and three-dimensional (3-D) quantitative phase imaging can be
      realized in the wide field of view, which means that the 3-D morphological
      parameters of biological cells without a staining process are obtained in real
      time. We report the complete 3-D quantitative phase imaging of blood coagulation
      structures by optical projection tomography in a flow cytometry using DHM.

PMID- 30302969
TI  - Procedural Fairness and the Coroner.
AB  - The hearing rule of procedural fairness applies to coroners' investigations and
      the findings made by coroners. Decisions by Australian and New Zealand appellate
      courts starting from the 1980s and early 1990s suggest that this will require
      interested parties to be accorded the opportunity to respond to any adverse
      findings, and probably comments, which a coroner is minded to make by being
      alerted in advance to what is proposed by the coroner. This editorial scrutinises
      decisions by the Victorian Supreme Court and Court of Appeal on the issue between
      2016 and 2018 against the backdrop of appellate decisions in South Australia and
      New Zealand, as well as in the context of the development of modern
      administrative law in both Australia and New Zealand. It identifies conceptual
      challenges that exist as a result of the recent case law for coroners' courts,
      pointing to the uncertainty of what are "adverse" findings and comments for these
      purposes, a lack of clarity as to who is entitled to procedural fairness in the
      inquisitorial context of a coronial investigation, the uncertain parameters of
      reputation for such purposes, vagueness as to what is required for coroners to
      discharge their obligations, and the logistical difficulties that compliance with
      such obligations will pose for timeliness of coronial findings.

PMID- 30302968
TI  - Holmium-YAG laser: impact of pulse energy and frequency on local fluid
      temperature in an in-vitro obstructed kidney calyx model.
AB  - During laser lithotripsy, energy is transmitted to both the stone and the
      surrounding fluid. As the energy is delivered, the temperature will rise.
      Temperatures >=60   degrees   C can cause protein denaturation. The objective of
      this study is to determine the time it takes from body temperature (37 degrees C)
      to 60 degrees C at various laser power settings. A Flexiva TracTip 200 optical
      fiber was submerged alongside a negative temperature coefficient-type thermistor
      in 4 mL of saline in a glass test tube. A Lumenis VersaPulse Powersuite 100-W
      holmium:yttrium aluminum garnet laser was activated at 0.2- to 1.5-J pulse
      energies, 6- to 50-Hz frequencies, and 2- to 22.5-W average power. Temperature
      readings were recorded every second from 37 degrees C until 60 degrees C. Time
      and heating rate were measured. The procedure was repeated three times for each
      setting. Average time from 37 degrees C to 60 degrees C for settings (1) 0.2 J/50
      Hz, (2) 0.6 J/6 Hz, (3) 1 J/10 Hz, and (4) 1.5 J/10 Hz was 60.3, 172.7, 58, and
      43.3 s, respectively. Time from 37 degrees C to 60 degrees C decreased as
      frequency increased for every given pulse energy. Average heating rate increased
      proportionally to power from 0.06 degrees C/s at 2 W to 0.74 degrees C/s at 22.5
      W. During laser lithotripsy, there is a rapid increase in the temperature of its
      surrounding fluid and temperatures >=60   degrees   C may be reached. This could
      have local tissue effects and some caution with higher power settings should be
      employed especially where irrigation is limited. Further studies incorporating
      irrigation and live tissue models may aid to further define the risks.

PMID- 30302970
TI  - The European Union General Data Protection Regulation (EU 2016/679) and the
      Australian My Health Record Scheme - A Comparative Study of Consent to Data
      Processing Provisions.
AB  - As a general rule, lawfulness of data processing under the European Union General
      Data Protection Regulation (EU 2016/679) (GDPR) is based on affirmative,
      unambiguous, voluntary, informed, and specific or "granular" consent to
      processing of their data, including health data, by individuals referred to as
      data subjects. The GDPR grants data subjects the legal right to specifically
      agree to (or refuse) having their data processed in any of the ways statutorily
      defined as "processing". Individuals also have the legal right to be fully
      informed about each and every intended use of their data by data processors and
      controllers, and the right to refuse such use. In Australia, once registered on
      the My Health Record (MHR) system, "healthcare recipients" as patients-cum-data
      subjects are called under the MHR scheme, have the right to remove documents from
      their MHR files and block some health care providers from accessing their data.
      However, this study demonstrates that the notion of "standing" consent that the
      MHR scheme appears to have created does not conform to any of the principles and
      rules governing data subjects' consent rights under GDPR.

PMID- 30302971
TI  - Geriatric Forensic Medicine - A Specialty that can no Longer Wait to be Realised.
AB  - The rise in the population and the growth in the proportion of the elderly in our
      population are changing the structure of many of our communities and placing
      increasing demands on our social and health care services. "Scandals" regarding
      conditions and standards of care in residential aged care facilities have raised
      concerns about the regulation, assessment and auditing of these community
      services for the elderly. At the same time longer working lives change the age
      factors related to employment opportunities and the cadre of older employees
      presents a different range of human resource issues and occupational health and
      safety problems for employers. While there is evidence that an older workforce
      can bring a wider experience and understanding of critical issues to many work
      disciplines, ageing practitioners may pose professional regulatory issues for the
      community when considerations of cognitive and technical/physical ability arise.
      It is in these settings that the need for a forensic focus on gerontology and
      medical geriatrics arises.

PMID- 30302972
TI  - "A Steadying Hand": Ascribing Speech Acts to Users of Predictive Speech Assistive
      Technologies.
AB  - Neuroprosthetic speech technologies are in development for patients suffering
      profound paralysis, such as can result from amyotrophic lateral sclerosis. These
      patients would be unable to speak without intervention, but with neurotechnology
      can be offered the chance to communicate. The nature of the technology introduces
      a neuroprosthesis that mediates neural activity to generate synthesised speech.
      How word prediction coheres with speaker intentions requires scrutiny. Some
      future forms of prostheses, using statistical language models to predict word
      patterns, could be thought of as participating with communicative intent - not
      merely channelling it. Concepts relating to vicarious liability, may serve to
      clarify these issues. This column shows how technology might interact with
      speaker intent in cases of delegated action, and how it should be seen as
      participating in the implementation of user "instructions".

PMID- 30302973
TI  - Australia's First Official Illicit Pill Testing at Canberra's Groovin' the Moo
      Music Festival: Legal Hurdles and Future Prospects.
AB  - The first official pill testing at an Australian music festival was conducted at
      Groovin' The Moo in Canberra on 29 April 2018. As the trial was the first of its
      kind in Australia, it was not without legal hurdles and uncertainty. Primarily,
      there was concern over the legal consequences for patrons participating in the
      pill testing, as well as the legal liability of those facilitating and conducting
      the testing. This article will discuss the legal hurdles that were overcome in
      order to facilitate the trial, and the future consequences and position of pill
      testing at Australian festivals.

PMID- 30302974
TI  - Moritz Meyer and the Medical Board: Preventing Refugee Doctors from Practising
      Medicine in Victoria, Australia, 1937-1958.
AB  - In 1937, the Medical Board of Victoria (the Board) declined to register Moritz
      Meyer to practise medicine in Victoria, Australia. Meyer was a Jewish doctor who
      had completed his medical degree in Germany and obtained postgraduate
      qualifications in Scotland. Meyer successfully challenged the Board's decision in
      the Supreme Court of Victoria and the Board's appeal against that decision to the
      High Court of Australia, which was dismissed. In response to Meyer's victory, the
      Board, under the influence and together with the British Medical Association,
      successfully lobbied the Victorian Parliament to prevent doctors from practising
      medicine in Victoria unless they had completed their studies in Victoria or in a
      country in which Victorian doctors, by virtue of their registration in Victoria,
      were entitled to practise medicine. Meyer's case received substantial press
      coverage, but historians have referred to it only in passing. This article fills
      a notable gap in the historiography about this period by illuminating the
      significance of Meyer's matter. It analyses the decisions in this case and
      considers their impact on European doctors who sought refuge in Victoria
      immediately before, during and after World War II, and on the medical profession
      and lay community. It then seeks to explain these reactions to Meyer's matter.

PMID- 30302975
TI  - Does Disciplinary Law Protect Us from False and Misleading Health Advertising?
AB  - Health-related advertisements should not mislead prospective patients. To do so
      may deprive patients of their ability to give or withhold consent to treatment
      and in the case of terminally ill patients, of the opportunity to accept and come
      to terms with the dying process. Patients should be able to expect that claims in
      health-related advertising are based on the most recent scientific evidence and
      are not predatory or exploitative. However, internet advertising and social media
      continue to provide opportunities for unscrupulous health practitioners to peddle
      their wares. This article considers whether disciplinary law effectively deals
      with false, misleading or deceptive health-related advertising in the context of
      regulated and unregulated practitioners as well as complementary and alternative
      medicine. It argues that consideration should be given to amending disciplinary
      law to specify what evidence is required to substantiate claims made in
      advertising.

PMID- 30302976
TI  - National Competition Policy and Australia's Health Care System: A Look at the
      Policy Landscape with New Eyes.
AB  - Australia spends nearly 10% of its gross domestic product on health services.
      With such a substantial financial commitment, even relatively minor improvements
      in efficiency, effectiveness and productivity can increase community welfare.
      Competition is a well-recognised policy lever implemented to achieve these goals
      in market economies. However, it has for many years struggled to gain traction in
      the health care sector. This article traces recent attempts to promote
      competition principles in Australia's health care sector. Highlighting where
      these attempts have stalled, it compares Australia's recent health reforms with
      those instituted in the United Kingdom's National Health Service where a sector
      specific competition regulator has been in place for several years. It concludes
      that there is room in Australia's regulatory landscape to improve public
      reporting and increased choice in health care. A sector-specific regulator is
      envisaged to support these important competition-based initiatives.

PMID- 30302977
TI  - Dental Health Workforce Regulation - How Amendments to the Health Practitioner
      Regulation National Law Act May Shape the Future of the Dental Profession.
AB  - Recent amendments to the Health Practitioner Regulation National Law Act adopt a
      number of recommendations published in the final report of the Independent review
      of the National Registration and Accreditation Scheme. The adopted
      recommendations are of interest because of their potential effect on the
      regulation of the dental profession and how they demonstrate the potential
      attenuation of the influence of the health professions in general in the arena of
      healthcare regulation. The wide-reaching effects of these changes and the impact
      they may have on the future direction of the dental profession in Australia are
      still uncertain, but are sure to be significant. This article will consider the
      changing role of the Dental Board in regulation and health workforce reform and
      show that the Dental Board is no longer the driver of dental workforce policy but
      plays a subordinate role to facilitate and implement health policy on direction
      from the AHWMC.

PMID- 30302978
TI  - In Sickness and in Prison: The Case for Removing the Medicare Exclusion for
      Australian Prisoners.
AB  - Many current and former prisoners experience significantly higher rates of
      physical and mental health problems than others in the community, and are among
      the most marginalised and disadvantaged people in society. This article argues
      that granting prison health services an exemption under s 19(2) of the Health
      Insurance Act 1973 Cth would make the Medicare Benefits Schedule and the
      Pharmaceutical Benefits Scheme-funded services available to prisoners who meet
      the eligibility criteria. Australian prisoners would then receive a level of care
      at least equivalent to that offered by community health services. Reducing health
      inequities that prisoners experience, particularly Indigenous prisoners, is
      essential for them continuing to receive health care following release and
      successfully reintegrating into the community. Further, granting the exemption
      would assist the Australian Government to meet its international human rights
      obligations to provide equitable health care for all Australians.

PMID- 30302979
TI  - "Mental Disorder" and Sentencing: Resolving the Definitional Problem.
AB  - Mental health problems affect the majority of people who face the sentencing
      process. The fact that a convicted offender has mental health problems may be
      taken into account in various ways: it may mitigate or aggravate the penalty, or
      may affect the type of sanction that is imposed or its conditions. At present,
      sentencing judges use a two-stage process to determine the effect (if any) that
      an offender's mental health problems should have on the sentencing determination.
      First, they ascertain whether the offender has a relevant mental health problem.
      If they find that he or she does, they then decide what effect that mental health
      problem should have on the sentencing determination. This article compares recent
      approaches that have been taken to the first stage of this process in Australia
      and Canada. It highlights difficulties with both approaches, and recommends
      replacing the current two-stage process with an integrated, single-stage
      approach.

PMID- 30302980
TI  - Biologics and Public Health: Prospects and Challenges.
AB  - Biotechnology has been used by humankind for thousands of years and it remains a
      very important part of human medicine. Biotechnology is particularly relevant to
      the creation of new medicines and vaccines. Biotechnology drugs or biologics are
      becoming increasingly popular in the life sciences sector. Biologics were
      estimated to account for US$289 billion pharmaceutical sales in 2014 and are
      projected to reach US$445 billion in 2019. It is also anticipated that biologics'
      share of global prescription and over-the-counter pharmaceutical sales will rise
      to 26% by 2019. Biological medicines are capable of being developed to cure life
      threatening diseases that used to be completely incurable. While biologics have
      unprecedented therapeutic effects, though, they also raise significant quality
      and patient safety issues. This article discusses some of the regulatory
      challenges relating to biologics. It also explores mechanisms that may be adopted
      to promote the development of new biologics and access to biological drugs
      especially in low income countries.

PMID- 30302981
TI  - The Privacy-Related Challenges Facing Medical Research in an Era of Big Data
      Analytics: A Critical Analysis of Australian Legal and Regulatory Frameworks.
AB  - This article examines the Australian approach to handling the complex privacy
      issues raised by Big Data analytics in health research. It analyses the privacy
      challenges posed by Big Data analytics and considers the privacy-related issues
      pertaining to the secondary use of health data for research purposes. It also
      examines the Australian regulatory regimes governing secondary uses of health
      data for research purposes contained in privacy legislation and human research
      guidelines, and includes a critique of a new criminal offence for re
      identification of de-identified datasets proposed by the Australian Government.
      The article concludes with suggestions for a reform process that enables
      responsible research into big health data while properly addressing the
      protection of privacy and confidentiality of such data.

PMID- 30302982
TI  - Australian Public Attitudes on Gene Editing of the Human Embryo.
AB  - Technology is now available which facilitates gene editing and has recently been
      applied internationally to embryos in the laboratory. A 2002 law in Australia
      prohibits making heritable changes in embryos, regardless of whether the treated
      embryo is discarded thereafter. We sought to begin to understand public opinion
      in Australia about this matter, using a questionnaire given to the audience
      attending a Q and A panel of experts. We found majority support for allowing
      heritable changes for health purposes. If this is confirmed in a larger survey of
      the population, we suggest the existing law should be reviewed.

PMID- 30302983
TI  - Regulating RNA Research and CRISPR Gene Drives to Combat Biosecurity Threats.
AB  - Recent technological breakthroughs in ribonucleic acid (RNA) research and the
      creation of synthetic gene drives using CRISPR/Cas9 have increased attention on
      the ethical and legal regulation of this field. RNA is now perceived as not
      merely a passive carrier of DNA information but especially through its propensity
      to mutate as a computation engine of cell biology, developmental biology and
      evolution. Synthetic Gene drives have been hailed as a potential strategy to
      reduce climate-change-mediated biosecurity threats such as spreading malaria and
      have attracted significant investment, with the Gates Foundation pledging US$75
      million and the Defense Advanced Research Projects Agency awarding US$65 million.
      Calls for a global moratorium on RNA-mediated genetic engineering may overstate
      the potential risks of the developing technology, but form a background to the
      contest between "process"- and "product" -based approaches to regulation, the
      former purportedly favoured by the public and regulatory agencies and the latter
      favoured by the broad scientific community and corporate investors. At stake may
      be the democratic legitimacy of and equitable access to a technology that could
      be important to reduce the incidence of biosecurity threats both globally and in
      Australia.

PMID- 30302984
TI  - Providing Palliative Care at the End of Life: Should Health Professionals Fear
      Regulation?
AB  - Anecdotal evidence from Australia and abroad suggests that health professionals
      may fear potential legal and/or professional repercussions if their patient dies
      after receiving pain relieving medication at the end of life. As a result,
      patients may be under-medicated and their pain and other symptoms not adequately
      relieved. The regulatory repercussions from inappropriate administration of
      medications are potentially broad and include criminal charges, civil negligence
      claims, coronial investigations and disciplinary proceedings. But despite these
      potentially serious repercussions, a review of publicly available cases in
      Australia reveals there has been comparatively little judicial or quasi-judicial
      scrutiny where over-medication is alleged to have resulted in a patient's death.
      In this article, we describe the regulatory framework that governs this field of
      medical practice and analyse the extent to which the actions of health
      professionals have been scrutinised, and the consequences of that scrutiny. We
      identify a number of themes arising from this analysis and conclude that fears of
      legal or professional repercussions are largely unfounded, and that existing laws
      and other forms of regulation should not inhibit the prescription and
      administration of adequate pain and other symptom relief to people at the end of
      life.

PMID- 30302985
TI  - The Role of the Medical Profession in Victorian Assisted Dying Law Reform.
AB  - The Voluntary Assisted Dying Act Vic will commence operation on 19 June 2019.
      Doctors were highly visible in the debate which informed the recent law reform
      process, and Victorian legislators relied considerably on the diverse views of
      the medical profession. It is important to pay attention to the role played by
      doctors in the legalisation of assisted dying in Victoria, not only because the
      current political environment suggests that further reforms may be likely in
      other Australian jurisdictions, but also because doctors' knowledge and expertise
      visibly contributed to the outcome of that process in Victoria. This article aims
      to map the participation of doctors in the recent law reform process to analyse
      how their professional attributes positioned them in the Victorian assisted dying
      space. It is suggested that doctors were afforded a place in law reform because
      of the routine acceptance of doctors as knowledge keepers in matters of life and
      death and an acknowledgment of the integral role of medical expertise in the
      legislation. A textual analysis of the Hansard record of the Victorian debate
      reflects that individual practitioner advocacy for legalisation prevailed over
      opposition by the national branch of the Australian Medical Association in the
      deliberations of parliamentarians.

PMID- 30302986
TI  - Sexual Assault Examination of the Unconscious Patient: A Legal, Ethical and
      Professional Grey-area for the Forensic Physician.
AB  - When treating unconscious patients believed to have been victims of sexual
      assault, forensic physicians must decide whether to conduct physical examinations
      in order to collect evidence while patients are unconscious and cannot consent.
      The choice is urgent: potential evidence may be lost before the patient regains
      the ability to consent. The physician's choice affects not only the patient's
      bodily integrity, but also their ability to pursue criminal and potentially civil
      justice remedies if they were assaulted. This article bases its discussion on one
      such real-life situation. It first examines ethical models relevant to deciding
      whether to take evidence and finds that no one approach produces morally
      satisfactory outcomes in every case. It then examines the legal framework guiding
      these decisions, finding that while collecting evidence without consent may well
      be permissible under New South Wales (NSW) legislation, relevant guidelines
      disallow it, placing physicians in a legal grey-area. The article concludes with
      practical recommendations to address these ethical, professional and legal
      challenges.

PMID- 30302987
TI  - Proteinuria in children with autosomal dominant polycystic kidney disease.
AB  - BACKGROUND: Proteinuria is a common complication in adults with autosomal
      dominant polycystic kidney disease (ADPKD) and serves as a risk factor for
      progression. However, proteinuria has rarely been examined in children with ADPKD
      and the type of proteinuria has not yet been investigated. The aim of the study
      was to assess the prevalence and to analyse the types of proteinuria in children
      with ADPKD. METHODS: Children with ADPKD followed-up in our tertiary centres
      during the years 2012-2013 were investigated in a cross-sectional study. Morning
      urine was tested for total protein (PROT), albumin (ALB) and alpha-1
      microglobulin (AMG). Renal function was assessed from serum creatinine as
      estimated glomerular filtration rate. RESULTS: Thirty-seven children of median
      age 11.2 (2.0-18.0) years were investigated. Median (range) PROT, ALB and AMG (in
      mg/mmol creatinine) were 15.1 (6.2-64.8), 2.54 (0.54-37.25) and 3.22 (0.04
      10.16), respectively. Pathological total proteinuria (>22) was found in 30% of
      children, albuminuria (>2.2) in 49% of children and alpha-1-microglobulinuria
      (>0.55) in 65% of children. No correlation was found between PROT, ALB or AMG and
      office blood pressure, kidney size or estimated glomerular filtration rate.
      CONCLUSIONS: Proteinuria in children with ADPKD is a frequent finding, the most
      common type is tubular proteinuria. It should be measured in all ADPKD children.

PMID- 30302988
TI  - Mononucleosis-related fatigue: supplementary management with Robuvit(r).
AB  - BACKGROUND: Infectious mononucleosis (IM) is a common disease of adolescents and
      young adults, characterized by a specific triad of symptoms represented by fever,
      sore throat and lymphadenopathy. IM may also affect older adults, with different,
      more intense signs and symptoms such as fatigue, general malaise, and diffuse
      body pain. The aim of thisfour-week-registry study was to evaluate the effects of
      Robuvit(r) supplementation on the main consequences of mononucleosis,
      particularly fatigue, in otherwise healthy adults. METHODS: All patients enrolled
      in this registry study experienced an episode of IM characterized by fatigue, a
      general feeling of unwellness, diffuse body and muscular pain, leukocytosis, and
      high levels of oxidative stress, at least 2 to 4 weeks prior to inclusion. Fever
      had already resolved at inclusion. All included patients were positively tested
      for the Epstein-Barr virus (EBV). Subjects were divided in two groups: those
      receiving the standard management (SM, N.=26; vitamin B, C, and D, balanced
      healthy diet, regular sleeping schedule, physical activity, 2 mg copper), and
      those treated with SM plus Robuvit(r) (N.=24) supplementation (300 mg/day).
      RESULTS: Supplementation with Robuvit(r) was safe, overall tolerability was good,
      and no side effects were reported. All patients completed the four-week
      treatment. After 4 weeks of treatment, a significant reduction in the rate of
      symptoms was evident in the Robuvit(r) group compared to the control group
      (P<0.05). CONCLUSIONS: Supplementation with Robuvit(r) is safe, well tolerated,
      and effective in controlling oxidative stress levels and improving fatigue and
      other symptoms related to IM episodes during the convalescence period.

PMID- 30302990
TI  - Amoxicillin/clavulanic acid-induced exfoliative dermatitis in a child.

PMID- 30302989
TI  - A rare cause of fever of unknown origin: hypohidrotic ectodermal dysplasia with a
      splice site mutation.

PMID- 30302991
TI  - Comparison between infantile hepatic hemangioendothelioma and hepatoblastoma in
      pediatric patients: clinical manifestations and contrast-enhanced computed
      tomography features.

PMID- 30302992
TI  - [THE ONSET OF INFECTIOUS ENDOCARDITIS WITH NEUROLOGICAL SYMPTOMS].
AB  - Despite the well known clinical and laboratory signs of infectious endocarditis,
      it remains one of the most difficult conditions in terms of diagnostics. A cause
      of its late diagnostics is polymorphism of the clinical picture accompanied,
      especially at early stages, by clinical "masks" (cardiac, pulmonary, renal,
      cerebral, etc.). We report a case of atypical onset of the disease with multiple
      thromboembolism of cerebral arteries, minimal clinical manifestations, and rapid
      destruction of the mitral valve that required surgical intervention.

PMID- 30302993
TI  - [DOMESTIC CLINICISM AND ITS APPLICATION].
AB  - Domestic clinicism is a methodology implying the maximum use of diagnostic and
      therapeutic potential of the physician in combination with the optimal
      application of laboratory and instrumental techniques for the choice of
      personified means of pharmaceutical and non-pharmaceutical treatment and
      prophylaxis of various diseases. It can not be applied under routine working
      conditions of a district doctor who has only 10-15 min to handle each patient.
      The currently adopted principle of organization of primary medical care: "the
      more patients the better", negatively affects the patients' health and
      emotionally discourage doctors.

PMID- 30302994
TI  - [SELFLESSNESS OF BESIEGED LENINGRAD: PROBLEMS OF MOTHERHOOD AND CHILDHOOD (ON THE
      OCCASION OF THE 72ND ANNIVERSARY OF LIFTING THE SIEGE)].
AB  - A review of documents on the peculiarities of obstetric and gynecological care in
      besieged Leningrad is presented with special reference to the data about the
      number of children born during blockade and their health status in the first
      months of life, the work of maternity hospitals, their number and personnel. The
      term "military time amenorrhea" coined during blockade is discussed.

PMID- 30302995
TI  - [E.O. MUKHIN - AN OUTSTANDING RUSSIAN ANATOMIST AND CLINICIAN (ON THE OCCASION OF
      HIS 250th BIRTHDAY ANNIVERSARY)].
AB  - Efim Osipovich Mukhin is an outstanding representative of Russian medical science
      who made an important contribution to the development of anatomo-physiological
      studies, establishment of surgery and traumatology as independent medical
      disciplines in this country, introduction of smallpox vaccination and aseptics
      into clinical practice as well as to the improvement of teaching medicine at
      universities.

PMID- 30302996
TI  - Phthalate and Organophosphate Plasticizers in Nail Polish: Evaluation of Labels
      and Ingredients.
AB  - In the 2000s, nail polish manufacturers started promoting "3-Free" products,
      phasing out three widely publicized toxic chemicals: toluene, formaldehyde, and
      dibutyl phthalate (DnBP). However, DnBP was sometimes replaced by another
      endocrine-disrupting plasticizer, triphenyl phosphate (TPHP). Many new " n-Free"
      labels have since appeared, without any standardization on which n chemicals are
      excluded. This study aimed to compare measured plasticizer content against nail
      polish labels. First, we summarized definitions of labels. Then, we measured 12
      phthalate and 10 organophosphate plasticizers in 40 nail polishes from 12 brands
      selected for popularity and label variety. We found labels ranging from 3- to 13
      Free; 10-Free was the most inconsistently defined (six definitions). Our samples
      contained TPHP and bis(2-ethylhexyl) phthalate (DEHP) at up to 7940 and 331
      MUg/g, respectively. The 5- to 13-Free samples had lower TPHP levels than
      unlabeled or 3-Free samples (median <0.002 vs 3730 MUg/g, p < 0.001). The samples
      that did not contain TPHP had higher DEHP levels (median 68.5 vs 1.51 MUg/g, p <
      0.05). We measured plasticizers above 100 MUg/g in five brands that did not
      disclose them and in two that excluded them in labels. This study highlights
      inconsistencies in nail polish labels and identifies TPHP and DEHP as ingredient
      substitutes for DnBP.

PMID- 30302997
TI  - Computation-Aided Design of Single-Atom Catalysts for One-Pot CO2 Capture,
      Activation, and Conversion.
AB  - Lowering the concentration of CO2 in atmosphere is a global concern but yet
      remains one of the most challenging processes in chemistry. Herein, we report a
      rational design of single-atom catalyst (SAC), namely, vanadium atom supported on
      newly synthesized beta12 boron monolayer (V1/beta12-BM), for one-pot CO2 capture,
      activation, and efficient conversion into methanol. Our first-principles
      computations reveal that strong interaction ensures V1/beta12-BM can capture CO2
      at ambient and elevated temperatures. Substantial charge transfer between
      V1/beta12-BM and CO2 triggers the activation of CO2 into anionic CO2-, which can
      be efficiently hydrogenated into CH3OH with an ultralow limiting potential of
      0.54 V and a rather low rate-determining barrier of 1.04 eV. Moreover, the
      adsorption of H2O molecules can make the reaction intermediates closer to the
      hydrogen source by the steric hindrance, which plays a key role in lowering the
      reaction barrier. Our findings present the first SAC for one-pot CO2 capture,
      activation, and conversion, which may open a new avenue for recycling CO2.

PMID- 30302998
TI  - Methionine-Containing Rhabdopeptide/Xenortide-like Peptides from Heterologous
      Expression of the Biosynthetic Gene Cluster kj12ABC in Escherichia coli.
AB  - Seven new methionine-containing rhabdopeptide/xenortide-like peptides (1-7) were
      identified from Escherichia coli expressing the rhabdopeptide/xenortide-like
      peptide biosynthetic gene cluster kj12ABC from Xenorhabdus KJ12.1. Their
      structures were elucidated by detailed HPLC-HR-MS/MS analysis and confirmed by
      chemical synthesis. Bioactivity tests of these first rhabdopeptide/xenortide-like
      peptide derivatives (2-7) showing methionine building blocks compared to the
      usually found derivatives containing exclusively hydrophobic amino acids such as
      valine, leucine, or phenylalanine revealed good activities of 2-7 against
      protozoan parasites and no cytotoxicity against mammalian L6 cells.

PMID- 30302999
TI  - 2-Azaallyl Anions, 2-Azaallyl Cations, 2-Azaallyl Radicals, and Azomethine
      Ylides.
AB  - This review covers the use of 2-azaallyl anions, 2-azaallyl cations, and 2
      azaallyl radicals in organic synthesis up through June 2018. Particular attention
      is paid to both foundational studies and recent advances over the past decade
      involving semistabilized and nonstabilized 2-azaallyl anions as key intermediates
      in various carbon-carbon and carbon-heteroatom bond-forming processes. Both
      transition-metal-catalyzed and transition-metal-free transformations are covered.
      Azomethine ylides, which have received significant attention elsewhere, are
      discussed briefly with the primary focus on critical comparisons with 2-azaallyl
      anions in regard to generation and use.

PMID- 30303000
TI  - Endoplasmic Reticulum-Targeted Ratiometric N-Heterocyclic Carbene Borane Probe
      for Two-Photon Microscopic Imaging of Hypochlorous Acid.
AB  - The naphthoimidazolium borane 4 is shown to be a selective probe for HOCl over
      other reactive oxygen species. Unlike other boronate-reactive oxygen species
      (ROS) fluorogenic probes that are oxidized by HOCl through a nucleophilic borono
      Dakin oxidation mechanism, probe 4 is distinguished by its electrophilic
      oxidation mechanism involving B-H bond cleavage. Two-photon microscopy
      experiments in living cells and tissues with the probe 4 demonstrate the
      monitoring of endogenous HOCl generation and changes in HOCl concentrations
      generated in the endoplasmic reticulum during oxidative stress situations.

PMID- 30303001
TI  - Circular Dichroism Photoswitching with a Twist: Axially Chiral Hemiindigo.
AB  - Chiroptical properties play a crucial role not only for molecular structures and
      their functions but also for advanced applications such as molecular sensing,
      absolute asymmetric synthesis, or information processing and storage.
      Manipulating chiroptical characteristics in a predictable and reversible fashion
      by outside means is therefore a highly desirable option to enhance the functions
      and reporting abilities of a molecular system. Herein, we present axially chiral
      hemiindigo photoswitches showing unusual chiroptical changes upon visible-light
      irradiation. While absorption remains high throughout the spectrum, the
      corresponding ECD signals can be reversibly erased and reestablished in an ON/OFF
      manner upon photoswitching. Taken together with exceptionally high thermal
      bistabilities, leading to half-lives of the metastable states up to 3400 years at
      ambient temperature, and high photoswitching quantum yields these chiral
      hemiindigos offer unique possibilities for, e.g., smart molecule, photonic
      materials, or sensing applications.

PMID- 30303002
TI  - Ancistrolikokine E3, a 5,8'-Coupled Naphthylisoquinoline Alkaloid, Eliminates the
      Tolerance of Cancer Cells to Nutrition Starvation by Inhibition of the
      Akt/mTOR/Autophagy Signaling Pathway.
AB  - PANC-1 human pancreatic cancer cells are characterized by their ability to
      proliferate aggressively under hypovascular and hypoxic conditions in the tumor
      microenvironment, displaying a remarkable tolerance to nutrition starvation. The
      antiausterity strategy is a new approach in anticancer drug discovery aiming at
      the identification of potent agents that inhibit preferentially the survival of
      tumor cells during a limited supply of nutrients and oxygen. The new 5,8'-coupled
      naphthyldihydroisoquinoline alkaloid ancistrolikokine E3 (4), isolated from the
      Congolese liana Ancistrocladus likoko, showed potent preferential cytotoxicity
      against PANC-1 cells under nutrient-deprived conditions, with a PC50 value of 2.5
      MUM, without exhibiting toxicity in normal, nutrient-rich medium. The compound
      was found to induce dramatic alterations in cell morphology, leading to cell
      death. Moreover, it inhibited significantly PANC-1 cell migration and colony
      formation in a concentration-dependent manner. This study on 4 provides the first
      live evidence of the effect of a naphthyldihydroisoquinoline alkaloid against
      PANC-1 cells in nutrient-deprived medium. Mechanistic investigations conducted
      suggest that compound 4 is a potent inhibitor of the activation of the Akt/mTOR
      pathway. Furthermore, it inhibited the expression levels of the key autophagy
      regulators Atg5, Atg12, Beclin-1, LC3-I, and LC3-II. The results demonstrated
      that ancistrolikokine E3 (4) is a potent early-stage inhibitor of the autophagy
      pathway in PANC-1 human pancreatic cancer cells. Ancistrolikokine E3 (4) and
      related naphthylisoquinoline alkaloids are promising potential lead compounds for
      anticancer drug development based on the antiausterity strategy.

PMID- 30303003
TI  - Boosting Tunable Syngas Formation via Electrochemical CO2 Reduction on Cu/In2O3
      Core/Shell Nanoparticles.
AB  - In this work, monodisperse core/shell Cu/In2O3 nanoparticles (NPs) were developed
      to boost efficient and tunable syngas formation via electrochemical CO2 reduction
      for the first time. The efficiency and composition of syngas production on the
      developed carbon-supported Cu/In2O3 catalysts are highly dependent on the In2O3
      shell thickness (0.4-1.5 nm). As a result, a wide H2/CO ratio (4/1 to 0.4/1) was
      achieved on the Cu/In2O3 catalysts by controlling the shell thickness and the
      applied potential (from -0.4 to -0.9 V vs reversible hydrogen electrode), with
      Faraday efficiency of syngas formation larger than 90%. Specifically, the best
      performing Cu/In2O3 catalyst demonstrates remarkably large current densities
      under low overpotentials (4.6 and 12.7 mA/cm2 at -0.6 and -0.9 V, respectively),
      which are competitive with most of the reported systems for syngas formation.
      Mechanistic discussion implicates that the synergistic effect between lattice
      compression and Cu doping in the In2O3 shell may enhance the binding of *COOH on
      the Cu/In2O3 NP surface, leading to the enhanced CO generation relative to Cu and
      In2O3 catalysts. This report demonstrates a new strategy to realize efficient and
      tunable syngas formation via rationally designed core/shell catalyst
      configuration.

PMID- 30303004
TI  - In-Situ Synthesis and High-Efficiency Photocatalytic Performance of Cu(I)/Cu(II)
      Inorganic Coordination Polymer Quantum Sheets.
AB  - Two-dimensional (2D) materials ultrathin quantum sheets have the advantage of
      elevating the catalysis performance and prominent edge effects, but most of them
      belong to element single valence materials. In this paper, the ultrathin
      Cu(I)/Cu(II) inorganic coordination polymer quantum sheet (ICPQS)
      {[CuII(H2O)4][CuI4(CN)6]} n is synthesized by controlling the appropriate molar
      ratio of raw material, reaction time, and temperature. Transmission electron
      microscopy (TEM) and atomic force microscope (AFM) analysis show that this ICPQS
      has a thickness of ~0.2 nm. Due to the fact that about 58.16% of the Cu(I)/Cu(II)
      is occupied in molecular structure and most of the metal active sites are fully
      utilized, this ICPQS can accelerate the photocatalytic degradation of methylene
      blue (MB) (K = 2.5 mg.L-1.min-1 at pH 3) and organic compounds in coking
      wastewater and biotreated coking wastewater. Basing on mixed valences, the ICPQS
      can use visible light to promote energy transfer and increase quantum efficiency,
      paving the way for developing the next-generation monolayer 2D mixed valence
      photocatalysts.

PMID- 30303005
TI  - C-F Bond Activation of P(C6F5)3 by Ruthenium Dihydride Complexes: Isolation and
      Reactivity of the "Missing" Ru(PPh3)3H(halide) Complex, Ru(PPh3)3HF.
AB  - The major product of the reaction between Ru(IMe4)2(PPh3)2H2 (1; IMe4 = 1,3,4,5
      tetramethylimidazol-2-ylidene) and P(C6F5)3 (PCF) is the five-coordinate complex
      Ru(IMe4)2(PF2{C6F5})(C6F5)H (2), which is formed via a complex series of C-F/P-C
      bond cleavage and P-F bond formation steps. In contrast, hydrodefluorination of
      all six ortho C-F bonds in PCF occurs with Ru(PPh3)4H2 to afford Ru(PPh3)3HF (3).
      NaBArF4 abstracted the fluoride ligand in 3 to give [Ru({eta6
      C6H5}PPh2)(PPh3)2H][BArF4], while B2pin2 reacted with 3 in C6D6 to yield a
      mixture of [Ru({eta6-C6D6)(PPh3)2H]+ and Ru(PPh3)4H2. The treatment of 3 with
      HBpin (5 equiv) and HSiR3 (R = Et, Ph; 2 equiv) afforded Ru(PPh3)3(sigma-HBpin)H2
      and Ru(PPh3)3(SiR3)3H3, respectively. No stable substitution products were
      generated when 3 was reacted with Me3SiX (X = CF3, C6F5).

PMID- 30303006
TI  - DNA Polymer Nanoparticles Programmed via Supersandwich Hybridization for Imaging
      and Therapy of Cancer Cells.
AB  - Spherical nucleic acid (SNA) constructs are promising new single entity
      materials, which possess significant advantages in biological applications.
      Current SNA-based drug delivery system typically employed single-layered ss- or
      ds-DNA as the drug carriers, resulting in limited drug payload capacity and
      disease treatment. To advance corresponding applications, we developed a novel
      DNA-programmed polymeric SNA, a long concatamer DNA polymer that is uniformly
      distributed on gold nanoparticles (AuNPs), by self-assembling from two short
      alternating DNA building blocks upon initiation of immobilized capture probes on
      AuNPs, through a supersandwich hybridization reaction. The long DNA concatamer of
      polymeric SNA enables to allow high-capacity loading of bioimaging and
      therapeutics agents. We demonstrated that both of the fluorescence signals and
      therapeutic efficacy were effectively inhibited in resultant polymeric SNA. By
      further modifying with the nucleolin-targeting aptamer AS1411, this polymeric SNA
      could be specifically internalized into the tumor cells through nucleolin
      mediated endocytosis and then interact with endogenous ATP to cause the release
      of therapeutics agents from long DNA concatamer via a structure switching,
      leading to the activation of the fluorescence and selective synergistic
      chemotherapy and photodynamic therapy. This nanostructure can afford a promising
      targeted drug transport platform for activatable cancer theranostics.

PMID- 30303007
TI  - Strategy for the Realization of Highly Efficient Solution-Processed All
      Fluorescence White OLEDs-Encapsulated Thermally Activated Delayed Fluorescent
      Yellow Emitters.
AB  - Fabrication of highly efficient all thermally activated delayed fluorescence
      (TADF) white organic light-emitting diodes (WOLEDs) through solution-process
      still remains a big challenge. Here, two encapsulated TADF molecules with a small
      singlet-triplet energy gap (Delta EST) and high photoluminescence quantum yield
      (PLQY) were designed and synthesized as yellow emitters for solution-processed
      WOLEDs. The high current, power, and external quantum efficiencies of 41.6 cd A
      1, 30.4 lm W-1, and 17.3% were achieved for the solution-processed all
      fluorescence WOLEDs with a single-emission layer. In contrast, even with the same
      Delta EST and PLQY, the corresponding unencapsulated parent emitters will account
      for nearly 50% loss of the potential device efficiency. This is for the first
      time that the small molecular TADF blue host and TADF yellow guest are used to
      construct solution-processed all-fluorescence WOLEDs, which exhibit high
      efficiency comparable with most of the vacuum-deposited all-fluorescence white
      devices. These results not only demonstrate the great potential of TADF emitters
      in achieving highly efficient solution-processed WOLEDs, but also testify the key
      role of molecular encapsulation in reducing polar-exciton quenching and enhancing
      electroluminescence performance.

PMID- 30303008
TI  - Innovation: Structural Proteomics Goes Global.

PMID- 30303009
TI  - Co2B and Co Nanoparticles Immobilized on the N-B-Doped Carbon Derived from Nano
      B4C for Efficient Catalysis of Oxygen Evolution, Hydrogen Evolution, and Oxygen
      Reduction Reactions.
AB  - A novel hybrid electrocatalyst of Co2B and Co nanoparticles immobilized on N-B
      doped carbon derived from nano-B4C (Co2B/Co/N-B-C/B4C) is in situ synthesized by
      pyrolysis of nano-B4C supporting Co(OH)2 nanoparticles with melamine. The Co2B
      and Co nanoparticles are formed and anchored on the generated N and B codoped
      carbon and undecomposed B4C. The hybrid exhibits remarkable catalytic
      performances toward the oxygen evolution reaction (OER) and oxygen reduction
      reaction (ORR)-a very small potential of 1.53 V at 10 mA cm-2 for the OER and a
      high catalytic kinetics and superior durability for the ORR-which are superior to
      the RuO2 and Pt/C catalyst, respectively. Most impressively, the hybrid delivers
      a very small potential gap of 710 mV, which is lower than those of most
      bifunctional electrocatalysts reported. In addition, the hybrid also shows a
      satisfying hydrogen evolution reaction performance offering a small overpotential
      of 220 mV at 10 mA cm-2 and wonderful stability. The excellent trifunctional
      catalytic performances issue from synergetic effects of Co2B, metal Co, Co/N
      doped carbon, and B self-doped carbon coexisting in the hybrid with good
      interaction mutually. This work provides a new-type efficient multifunctional
      catalyst for regenerative fuel cell and overall water-splitting technologies.

PMID- 30303010
TI  - Preparation of Bi0.15Fe0.15TiO2 Nanocomposites for the Highly Selective
      Enrichment of Phosphopeptides.
AB  - Novel Bi0.15Fe0.15TiO2 nanocomposites (B0.15F0.15TNs) were synthesized for the
      first time by a modified sol-gel technology and successfully applied to selective
      extraction and enrichment of phosphopeptides from digested protein mixture
      solutions and real samples (tissue protein extract from human liver). The
      codoping of Bi and Fe into TiO2 results in a significant enhancement in both the
      enrichment efficiency and selectivity. Compared with the commercial available
      TiO2 extractant, the proposed B0.15F0.15TNs possess a lower detection limit (2 *
      10-9 M) and higher selectivity at a low weight ratio of 1:1200
      (phosphopeptides/nonphosphopeptides). Additionally, a total of 223
      phosphorylation sites were identified from the human liver lysate after
      enrichment by the B0.15F0.15TNs. In addition, the synthesis of B0.15F0.15TNs is
      quite easy, of high yield, and inexpensive.

PMID- 30303011
TI  - Hongyacha, a Naturally Caffeine-Free Tea Plant from Fujian, China.
AB  - Hongyacha (HYC) is a type of new wild tea plant discovered in Fujian Province,
      China. This tea is helpful to the healing or prevention of disease in its
      original growing area. However, research on this tea is limited. Our results
      showed that HYC displayed obvious differences in its morphological
      characteristics compared with Cocoa tea ( Camellia ptilophylla Chang), a famous
      caffeine-free tea plant in China. Theobromine and trans-catechins, but not
      caffeine and cis-catechins, were the dominant purine alkaloids and catechins
      detected in HYC. HYC might contain abundant gallocatechin-(4 -> 8)-gallocatechin
      gallate, 1,3,4,6-tetra- O-galloyl-beta-d-glucopyranose, and (-)-gallocatechin-3,5
      di- O-gallate, which were not detected in regular tea. We also found that the
      TCS1 of HYC was distinct, and the responding recombinant protein exhibited only
      theobromine synthase activity. The obtained results showed that HYC is a new kind
      of caffeine-free tea plant and may be used for scientific protection and
      efficient utilization in the future.

PMID- 30303012
TI  - Filbertone: A Review.
AB  - This comprehensive review of filbertone, a principal flavor compound of hazelnut,
      evaluates the current state of the art of all relevant aspects of the title
      molecule: its occurrence and properties, laboratory preparation and bulk
      synthesis, analytical issues regarding stereochemistry and purity, sensory
      evaluation, and practical uses. Comparisons are made between different synthetic
      approaches, and a critical assessment of various applications is presented.

PMID- 30303013
TI  - Absorption of 1-Dicysteinethioacetal-5-Hydroxymethylfurfural in Rats and Its
      Effect on Oxidative Stress and Gut Microbiota.
AB  - The absorption of a 5-hydroxymethylfurfural (HMF)-cysteine adduct, 1
      dicysteinethioacetal-5-hydroxymethylfurfural (DCH), and its effect on antioxidant
      activity and gut microbiota were investigated. Results indicated that DCH is more
      easily absorbed in rats than HMF. Serum DCH concentrations were 15-38-fold of HMF
      concentrations from 30 to 180 min after intragastrical administration at the
      level of 100 mg/kg of body weight, and 2.7-4.5% of absorbed DCH was converted to
      HMF. The malondialdehyde content in the plasma, heart, liver, and kidneys
      significantly increased after drug (100 mg/kg of bw) administration for 1 week,
      suggesting that HMF and DCH were oxidative-stress-inducing agents, instead of
      antioxidant agents, in rats. HMF and DCH also modulated gut microbiota. HMF
      promoted the growth of Lactobacillus, Tyzzerella, Enterobacter, and
      Streptococcus. DCH increased the ratio of Firmicutes/ Bacteroidetes and promoted
      the growth of Akkermansia, Shigella, and Escherichia while inhibiting the growth
      of Lactobacillus.

PMID- 30303014
TI  - Toxicokinetics and Metabolism of 3-Monochloropropane 1,2-Diol Dipalmitate in
      Sprague Dawley Rats.
AB  - Fatty acid esters of 3-monochloropropane 1,2-diol (3-MCPD) are a group of
      processing-induced toxicants. To better clarify their possible toxicological
      effects and mechanisms, it is important to investigate their absorption,
      distribution, metabolism, and excretion. In this study, the kinetic parameters of
      3-MCPD dipalmitate in Sprague Dawley (SD) rat plasma were determined using
      ultraperformance liquid chromatography-triple quadrupole mass spectrometry. 3
      MCPD dipalmitate was absorbed in rats with a Cmax of 135.00 ng/mL, a T1/2 of 3.87
      h, a Tmax of 2.5 h, an MRT of 5.08 h, a CL of 3.50 L/h/g, a Vd of 21.34 L/g, and
      an AUC0-infinity of 458.47 h.ng/mL. A total of 17 metabolites were identified,
      and 16 of them were reported for the first time. Furthermore, these metabolites
      were examined for their presences in the liver, kidney, testis, brain, spleen,
      thymus, intestine, plasma, feces, and urine samples 2, 6, 12, 24, and 48 h after
      oral administration of 3-MCPD dipalmitate using Metabolynx software.

PMID- 30303015
TI  - One-Pot Synthesis of 3-Difluoromethyl Benzoxazole-2-thiones.
AB  - A one-pot strategy for the diversified synthesis of 3-difluoromethyl benzoxazole
      2-thiones is reported. The reaction of 2-aminophenol, sodium
      chlorodifluoroacetate, and elemental sulfur in the presence of NaO t-Bu gives
      exclusively 3-difluoromethyl benzoxazole-2-thiones in good yield (up to 98%). The
      mechanism of this reaction presumably involves first cyclization of 2
      aminophenols with thiocarbonyl fluoride, followed by N-difluoromethylation with
      difluorocarbene. The developed synthetic procedures are versatile, robust, and
      easily scalable for the synthesis of 3-difluoromethyl benzoxazole-2-thione
      derivatives, some of which have shown insecticidal activities.

PMID- 30303016
TI  - Phosphine-Catalyzed [3 + 2] Annulation of 2-Hydroxy-1,4-naphthaquinones and
      Allenoate: An Allene-Alkene [3 + 2] Annulation Mechanism Involving Consecutive
      gamma-Addition-Aldol Reaction.
AB  - A diastereoselective construction of biologically important tetrahydrocyclopenta[
      b]naphthalene derivatives has been achieved via a phosphine-catalyzed [3 + 2]
      annulation of 2-hydroxy-1,4-naphthaquinone derivatives and allenoate. Various
      tetrahydrocyclopenta[ b]naphthalene derivatives containing contiguous quaternary
      carbon centers are obtained in good yields with excellent diastereoselectivities.
      The asymmetric version gave the chiral product in up to 57% ee under catalysis of
      Kwon chiral phosphine. The reaction undergoes a reaction mechanism involving
      consecutive gamma-addition-aldol reaction.

PMID- 30303017
TI  - Appraisals of dependent stressor controllability and severity are associated with
      depression and anxiety symptoms in youth.
AB  - BACKGROUND AND OBJECTIVES: Stress is well established as a strong risk factor for
      internalizing psychopathology. Learned helplessness research demonstrates that
      perceived controllability of stressors affects internalizing symptoms.
      Furthermore, subjective perceived stress is associated with psychopathology.
      However, most recent research has focused on measuring the frequency and expert
      rated severity of stressful life events despite evidence for the importance of
      stress perceptions. The present study brings together past and current
      literatures to investigate the importance of perceived severity and
      controllability of recent life events in the association between stressors and
      internalizing symptoms. DESIGN AND METHODS: We used a revised version of the
      Adolescent Life Events Questionnaire (ALEQ) that asked participants (ages 13-22,
      N = 328) to rate the frequency of 65 stressful events typical to youth, as well
      as the perceived stressfulness and control they felt over each event. Events were
      categorized prior to analysis as dependent (self-generated), independent
      (fateful) or neither. RESULTS: Controllability and severity appraisals were
      associated with depression and anxiety symptoms, controlling for stressor
      frequency (which also predicted symptoms), for dependent but not independent
      stressors. CONCLUSIONS: These results highlight the importance of controllability
      and severity appraisals as potential risk factors for internalizing disorders,
      exposing a potential target for therapy.

PMID- 30303018
TI  - Pleiotropy of the Drosophila melanogaster foraging gene on larval feeding-related
      traits.
AB  - Little is known about the molecular underpinning of behavioral pleiotropy. The
      Drosophila melanogaster foraging gene is highly pleiotropic, affecting many
      independent larval and adult phenotypes. Included in foraging's multiple
      phenotypes are larval foraging path length, triglyceride levels, and food intake.
      foraging has a complex structure with four promoters and 21 transcripts that
      encode nine protein isoforms of a cGMP dependent protein kinase (PKG). We
      examined if foraging's complex molecular structure underlies the behavioral
      pleiotropy associated with this gene. Using a promotor analysis strategy, we
      cloned DNA fragments upstream of each of foraging's transcription start sites and
      generated four separate forpr-Gal4s. Supporting our hypothesis of modular
      function, they had discrete, restricted expression patterns throughout the larva.
      In the CNS, forpr1-Gal4 and forpr4-Gal4 were expressed in neurons while forpr2
      Gal4 and forpr3-Gal4 were expressed in glia cells. In the gastric system, forpr1
      Gal4 and forpr3-Gal4 were expressed in enteroendocrine cells of the midgut while
      forpr2-Gal4 was expressed in the stem cells of the midgut. forpr3-Gal4 was
      expressed in the midgut enterocytes, and midgut and hindgut visceral muscle.
      forpr4-Gal4's gastric system expression was restricted to the hindgut. We also
      found promoter specific expression in the larval fat body, salivary glands, and
      body muscle. The modularity of foraging's molecular structure was also apparent
      in the phenotypic rescues. We rescued larval path length, triglyceride levels
      (bordered on significance), and food intake of for0 null larvae using different
      forpr-Gal4s to drive UAS-forcDNA. In a foraging null genetic background, forpr1
      Gal4 was the only promoter driven Gal4 to rescue larval path length, forpr3-Gal4
      altered triglyceride levels, and forpr4-Gal4 rescued food intake. Our results
      refine the spatial expression responsible for foraging's associated phenotypes,
      as well as the sub-regions of the locus responsible for their expression.
      foraging's pleiotropy arises at least in part from the individual contributions
      of its four promoters.

PMID- 30303020
TI  - Access block to psychiatric inpatient admission: Implications for national mental
      health service planning.

PMID- 30303019
TI  - Does Patient-centered Care Change Genital Surgery Decisions? The Strategic Use of
      Clinical Uncertainty in Disorders of Sex Development Clinics.
AB  - Genital surgery in children with ambiguous or atypical genitalia has been marred
      by controversies about the appropriateness and timing of surgery, generating
      clinical uncertainty about decision making. Since 2006, medical experts and
      patient advocates have argued for putting the child's needs central as patient
      centered care. Based on audio recordings of 31 parent-clinician interactions in
      three clinics of disorders of sex development, we analyze how parents and
      clinicians decide on genital surgery. We find that clinicians and parents aim for
      parent-centered rather than infant-centered care. Parents receive ambivalent
      messages about surgery: while clinicians express caution, they also present the
      surgery as beneficial. We examine how parents and clinicians reach agreement
      about surgery-differentiating parents who push strongly for surgery from parents
      who do not express any preconceived preferences about surgery and parents who
      resist surgery. We conclude that clinicians use clinical uncertainty about
      surgery strategically to direct parents toward perceived clinically appropriate
      decisions.

PMID- 30303022
TI  - Cost-effectiveness of pembrolizumab versus brentuximab vedotin for patients with
      relapsed or refractory classical Hodgkin's lymphoma: a United States payer
      perspective.
AB  - AIMS: Patients with classical Hodgkin's lymphoma (cHL) who have relapsed after or
      are ineligible for autologous stem cell transplantation (ASCT) have limited
      treatment options and generally a poor prognosis. Pembrolizumab was recently
      approved in the US for the treatment of such patients having demonstrated
      clinical benefit and tolerability in relapsed/refractory cHL; however, the cost
      effectiveness of pembrolizumab in this population is currently unknown. MATERIALS
      AND METHODS: A three-state Markov model (progression-free [PF], progressed
      disease, and death) was developed to assess the cost-effectiveness of
      pembrolizumab (200 mg) vs brentuximab vedotin (BV; 1.8 mg/kg) in patients with
      relapsed/refractory cHL after ASCT who have not received BV post-ASCT over a 20
      year time horizon from a US payer perspective. PF survival was modeled using a
      naive indirect treatment comparison of data from KEYNOTE-087 and the SG035-003
      trial. Post-progression survival was modeled using data from published
      literature. Costs (drug acquisition and administration, disease management,
      subsequent treatment, and adverse events) and outcomes were discounted at an
      annual rate of 3.0%. Uncertainty surrounding cost-effectiveness was assessed via
      probabilistic, deterministic, and scenario analyses. RESULTS: In the base case,
      pembrolizumab was predicted to yield an additional 0.574 life-years (LYs) and
      0.500 quality-adjusted life-years (QALYs) vs BV and cost savings of $63,278. Drug
      acquisition costs were the biggest driver of incremental costs between
      strategies. Pembrolizumab had a 99.6% probability of being cost-effective
      compared with BV at a willingness-to-pay threshold of $20,000/QALY and dominated
      BV in all scenarios tested. LIMITATIONS: The analysis was subject to potential
      bias due to the use of a naive indirect treatment comparison and, given the
      current immaturity of OS in KEYNOTE-087, PPS was assumed equivalent across both
      treatments. CONCLUSION: Pembrolizumab is a cost-effective alternative to BV for
      patients with relapsed/refractory cHL after ASCT.

PMID- 30303023
TI  - Can Better Emotion Regulation Protect Against Interpersonal Violence in Homeless
      Youth Social Networks?
AB  - Homeless youth experience all types of violence at higher rates than their housed
      counterparts. This is typically the result of many contributing factors including
      childhood experiences of trauma, subsistence survival strategies, and exposure to
      perpetrators while living on the streets. Reducing violence in the lives of
      homeless youth is imperative and can contribute to a young person's ability to
      safely and successfully exit the streets and lead a long and productive life in
      society. However, developing public health and social interventions to reduce
      violence in adolescent and young adult populations is difficult due to the
      complex interplay of extrinsic and intrinsic drivers of this phenomenon. Los
      Angeles area homeless youth ( N = 366) were asked questions regarding recent
      violence experiences, emotion regulation, and their social network. Multivariable
      logistic regressions tested the overall effect of emotion regulation on violence,
      controlling for age, gender, race, sexual identity, experience of childhood
      abuse, and data collection site. In this sample, 56% of youth endorsed fighting
      in the previous year, and those who reported more difficulties with emotion
      regulation were significantly more likely to fight. In addition, youth who scored
      below the mean on difficulties with regulation and belonged to networks
      characterized by low-difficulty peers were 60% less likely to report fighting.
      Emotion regulation skills represent a malleable target for intervention that may
      contribute to reduced propensity for violence in this population. Implications
      for network-based interventions to improve individual emotion regulation and
      reduce overall violence among homeless youth and other at-risk populations are
      discussed.

PMID- 30303021
TI  - Botanical Formula LCS101: A Multi-Targeted Approach to Cancer Care.
AB  - BACKGROUND AND PURPOSE: LCS101 is a botanical formula extracted from 14 botanical
      components. While conventional oncology focuses on targeted medicine, research on
      LCS101 adopts a multi-targeted approach, examining its preclinical (in vitro, in
      vivo, and ex vivo) and clinical (randomized controlled trial, pragmatic) effects.
      This includes examining the formula's impact on the immune system, selective
      anticancer effects, and improved chemotherapy-related symptoms and quality of
      life. Effects on the Immune System: In murine splenic cell cultures, LCS101
      significantly increased T-cell proliferation and macrophage tumor necrosis factor
      alpha production. Blood samples from healthy volunteers exposed to LCS101 showed
      a dose-dependent increase in natural killer cell activity; and a randomized
      controlled trial showed significantly lower rates of leucopenia/neutropenia and
      anemia in patients with breast cancer undergoing chemotherapy. Selective
      Anticancer Effects: In vitro LCS101 demonstrated selective growth inhibition (on
      XTT viability assay) in human breast and prostate cancer cell lines, without any
      harmful effects on normal human epithelial cells. The anticancer effects were
      attributed to reactive oxygen species activity. Cytotoxic effects of doxorubicin
      and 5-fluorouracil on breast cancer cell lines were significantly increased
      following exposure to LCS101, with a protective effect in normal cells. Symptom
      Relief and Quality of Life: Clinical research shows that patients taking LCS101
      during chemotherapy are less likely to report symptoms such as fatigue, pain,
      nausea and vomiting. CONCLUSION: LCS101 exhibits multi-targeted effects, with
      significant implications for cancer care. Further research is needed to better
      understand the impact of these findings.

PMID- 30303024
TI  - BMI Trajectories in Adulthood: The Intersection of Skin Color, Gender, and Age
      among African Americans.
AB  - This study addresses three research questions critical to understanding if and
      how skin color shapes health among African Americans: (1) Does skin color predict
      trajectories of body mass index (BMI) among African Americans across ages 32 to
      55? (2) To what extent is this relationship contingent on gender? (3) Do
      sociodemographic, psychosocial, and behavioral factors explain the skin color-BMI
      relationship? Using data from the Coronary Artery Risk Development in Young
      Adults Study and growth curve models, results indicate that dark-skinned women
      have the highest BMI across adulthood compared to all other skin color-gender
      groups. BMI differences between dark- and lighter-skinned women remain stable
      from ages 32 to 55. Among men, a BMI disadvantage emerges and widens between
      light- and dark-skinned men and their medium-skinned counterparts. Observed
      sociodemographic characteristics, stressors, and health behaviors do not explain
      these associations. Overall, findings suggest that skin color- and gender
      specific experiences likely play an important role in generating BMI inequality.

PMID- 30303025
TI  - "I Thought It Was Normal": Adolescents' Attempts to Make Sense of Their
      Experiences of Domestic Violence in Their Families.
AB  - This article describes the experience and impact of domestic violence on
      adolescents using qualitative methodology. It explores the meanings that
      adolescents give to their experiences and how this may relate to the impact of
      those experiences. Five adolescents who were receiving interventions within child
      and adolescent mental health services were interviewed about their experiences of
      domestic violence and the interviews were analyzed using interpretative
      phenomenological analysis (IPA). The results suggest that adolescents had a range
      of thoughts and feelings connected to their experiences, and that the impact of
      the domestic violence may be related to the different meanings that the
      adolescents gave to their experiences and how they made sense of those
      experiences. The results are explored using theories such as Grych and Fincham's
      Cognitive-Contextual Model; Watkin's elaborated Control Theory; and the work on
      posttraumatic growth. Research and clinical implications are discussed in the
      light of the results.

PMID- 30303026
TI  - The Contingent Effect of Guardianship on Victimization: An Examination of People
      With and Without Mental Health Problems.
AB  - Mixed effects of guardianship on victimization have been found in the literature.
      It is possible that these divergent findings have emerged because research has
      not recognized how the need for guardianship may shape the results. That is,
      individuals who are not suitable targets (i.e., individuals without mental health
      problems-those who are not perceived as vulnerable or incapable of defending
      themselves) do not need guardianship, resulting in null findings for the
      protective effects of guardianship on victimization. We examine the possibility
      that mental health problems and guardianship interact to produce victimization in
      the Life Opportunities Survey, a nationally representative survey of individuals
      in the United Kingdom ( N = 27,516). Logistic regression analyses support our
      hypothesis that the effects of guardianship on victimization, which is measured
      as violence or the threat of violence against an individual, are contingent on
      the presence of mental health problems (i.e., any emotional or psychological
      health condition). The risk of victimization for those with mental health
      problems who had guardianship was substantially lower than for those with mental
      health problems who lacked guardianship (11.5% vs. 17%, respectively). We discuss
      this finding in light of routine activities theory and crime prevention for
      people with mental health problems.

PMID- 30303027
TI  - Pathology of clade 2.3.2.1 avian influenza virus (H5N1) infection in quails and
      ducks in Bangladesh.
AB  - We performed pathological and molecular virological investigation of three
      outbreaks of highly pathogenic avian influenza (HPAI) in a quail farm and two
      duck farms of Mymensingh and Netrokona districts of Bangladesh in 2011. HPAI
      viruses of subtype H5N1 were detected from all three outbreaks and phylogenetic
      analysis of HA gene sequence placed the viruses into clade 2.3.2.1. The outbreak
      in the quail farm was characterized by acute death with 100% mortality within two
      days. Marked haemorrhages and congestion with necrotic and inflammatory lesions
      in the respiratory tract, liver, pancreas and kidneys were the major gross and
      histopathological lesions. In the case of ducks, nervous signs were the
      remarkable clinical manifestations and the mortality was around 10%. No
      significant gross lesions were observed at necropsy. Non-purulent encephalitis
      with gliosis and neuronal degeneration was observed on histopathological
      examination. By immunohistochemistry, viral antigen could be detected in
      different organs of both quails and ducks. This study records varying clinical
      and pathological manifestations of HPAI in ducks and quails following natural
      infection with the same strain of the virus. RESEARCH HIGHLIGHTS HPAIV of clade
      2.3.2.1 was detected from clinical outbreaks in quails and ducks Sudden death
      with severe haemorrhages in various organs was found in quails Pronounced nervous
      signs with non-purulent encephalitis were observed in ducks Viral antigen could
      be localized in different organs by immunohistochemistry.

PMID- 30303028
TI  - Primary Care Pharmacist Services Align With Payment Reform and Provider "Joy of
      Practice".
AB  - The implementation and expansion of primary care (PC) pharmacist medication
      optimization and management services has been hindered mainly by the lack of a
      payment mechanism for PC providers to engage pharmacist services. If pharmacists
      expect to be included in new PC team-based payment models, we need to actively
      engage in ongoing PC practice transformation discussions with PC organizational
      leaders. In this commentary, examples of integrated PC pharmacist services and
      payment models are provided to (1) reinforce the feasibility of pharmacist
      integration into expanded PC teams and (2) share with PC leaders, payers, and
      policy makers.

PMID- 30303029
TI  - Improving Pediatric Sepsis Treatment Using a Novel, Guideline-Based Pro Forma.

PMID- 30303030
TI  - Periostin alters transcriptional profile in a rat model of isoproterenol-induced
      cardiotoxicity.
AB  - Periostin is an extracellular matrix protein from the fasciclin family that
      guides cellular trafficking and extracellular matrix organization. Periostin
      stimulates mature cardiomyocytes to reenter the cell cycle. The molecular
      mechanism behind such stimulation remains to be explored. A DNA microarray
      technology constituting 30,429 gene-level probe sets was utilized to investigate
      effects of recombinant murine periostin peptide on the gene expression pattern in
      a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was
      performed on 84 adult male Sprague-Dawley rats in four groups ( n = 21): (1)
      control group, (2) only periostin applied group, (3) ISO cardiotoxicity group,
      and (4) ISO + periostin group. The experiment was continued for 28 days, and rats
      were killed on days 1, 7, and 28 ( n = 7). Microarray analyses revealed that
      periostin significantly altered the expression of at least +/-2-fold of 2474
      genes in the ISO + periostin group compared to the ISO cardiotoxicity group of
      which 521 genes altered out of 30,429 gene-level probe sets. Ingenuity pathway
      analysis indicated that multiple pathway networks were affected by periostin,
      with predominant changes occurring in the expression of genes involved in
      oxidative phosphorylation, oxidative stress, fatty acid metabolism, and TNF-alpha
      NF-kappaB signaling pathways. These findings indicate that periostin alters gene
      expression profile in the ISO-induced myocardial injury and modulates local
      myocardial inflammation, possibly mitigating inflammation through TNF-alpha NF
      kappaB signaling pathway along with a decreased Casp7 activity and apoptotic cell
      death.

PMID- 30303031
TI  - Public Stranger Violence-What Makes You Vulnerable?A Comparison of Perspectives
      From Young Adults and Industry Experts.
AB  - The purpose of this study was to determine the situational and individual factors
      that influence vulnerability to public stranger violence (PSV) from the
      perspective of young adults and industry professionals. In total, 25 young adults
      aged between 18 and 29 years formed one sample and participated in one of four
      focus groups. The second sample consisted of 10 industry professionals with
      backgrounds in policing, corrections, and forensic psychology. Each professional
      participated in an individual semistructured interview. Both samples were asked
      questions regarding vulnerability and safety in public, where responses were
      analyzed using a thematic analysis. Multiple themes were identified and
      categorized into situational and individual factors associated with
      victimization. Situational factors referred to aspects of the environment that
      may influence vulnerability to PSV and included visibility, location, and level
      of support for potential victims. Individual factors referred to aspects about
      the person that may influence vulnerability to PSV and included unpredictability,
      ease of target, stereotypes, in-groups versus out-groups, distractions, and
      personality traits. Although both samples identified similar situational factors,
      young adults were found to be either unaware of individual factors identified by
      industry professionals as influencing vulnerability or at least misunderstood
      some of these factors. This is problematic as young adults may be basing their
      public behaviors on misinformation that may in fact increase, rather than
      decrease, vulnerability to PSV. The findings from this study have implications
      for the design of personal safety programs as well as community-based
      interventions to reduce vulnerability, the prevalence of PSV, and the negative
      outcomes associated with PSV, including anxiety and fear of crime.

PMID- 30303033
TI  - Circulating long non-coding RNAs: could they be a useful tool for cancer therapy
      monitoring?

PMID- 30303032
TI  - Chronic myocardial infarction changed the excitatory-inhibitory synaptic balance
      in the medial prefrontal cortex of rat.
AB  - The medial prefrontal cortex is a key area for the regulation of pain and
      emotion. However, the functional involvement of the medial prefrontal cortex for
      visceral nociception, at the neuronal or synaptic level, is obscure yet. In the
      present study, the properties of excitatory and inhibitory synaptic transmission
      within the layer II/III of rat medial prefrontal cortex after chronic myocardial
      infarction were studied. It is found that the excitation-inhibition ratio of the
      medial prefrontal cortex was greatly changed, with enhanced excitation and
      decreased inhibition inputs to the pyramidal cells of the medial prefrontal
      cortex, which largely due to decreased spike firing in gamma-aminobutyric acid
      ergic neurons. Behaviorally, inhibition of gamma-aminobutyric acid-ergic synaptic
      transmission alleviated the visceral pain and anxiety. It is thus for the first
      time showing that the excitation-inhibition ratio is increased in the medial
      prefrontal cortex after chronic myocardial infarction, which may come from the
      reduced intrinsic activity of gamma-aminobutyric acid-ergic neurons and is
      important for regulating the angina pectoris and anxiety induced by chronic
      myocardial infarction.

PMID- 30303034
TI  - Echinacea biotechnology: advances, commercialization and future considerations.
AB  - CONTEXT: Plants of the genus Echinacea (Asteraceae) are among the most popular
      herbal supplements on the market today. Recent studies indicate there are
      potential new applications and emerging markets for this natural health product
      (NHP). OBJECTIVE: This review aims to synthesize recent developments in Echinacea
      biotechnology and to identify promising applications for these advances in the
      industry. METHODS: A comprehensive survey of peer-reviewed publications was
      carried out, focusing on Echinacea biotechnology and impacts on phytochemistry.
      This article primarily covers research findings since 2007 and builds on earlier
      reviews on the biotechnology of Echinacea. RESULTS: Bioreactors, genetic
      engineering and controlled biotic or abiotic elicitation have the potential to
      significantly improve the yield, consistency and overall quality of Echinacea
      products. Using these technologies, a variety of new applications for Echinacea
      can be realized, such as the use of seed oil and antimicrobial and immune
      boosting feed additives for livestock. CONCLUSIONS: New applications can take
      advantage of the well-established popularity of Echinacea as a NHP. Echinacea
      presents a myriad of potential health benefits, including anti-inflammatory,
      anxiolytic and antibiotic activities that have yet to be fully translated into
      new applications. The distinct chemistry and bioactivity of different Echinacea
      species and organs, moreover, can lead to interesting and diverse commercial
      opportunities.

PMID- 30303035
TI  - "Why Did She Talk to Him Again?" The Effects of the Justice Motive, Relationship
      Type, and Degree of Postassault Contact on Perceptions of Sexual Assault.
AB  - Victim blaming attitudes are prevalent within the criminal justice system where
      survivor behavior before, during, and following an assault is heavily
      scrutinized. Although dispositional characteristics (e.g., strength of one's
      justice motive) and characteristics of the assault (e.g., the type of
      relationship between a survivor and an offender) have been found to predict the
      degree of victim blaming, the effects of these variables on sexual assault myth
      endorsement are unclear. In addition, a variable that has not been examined in
      past literature is the degree of contact maintained between a survivor and
      offender after the assault. The purpose of the current study was to examine the
      extent to which the justice motive (strong vs. weak), the relationship between a
      fictional survivor and an offender (strangers vs. intimate partners), and contact
      between a survivor and offender postassault (contact vs. no contact) influenced
      endorsement of sexual assault myths. Undergraduate students read a vignette
      depicting a fictional sexual assault that varied with respect to the relationship
      and the amount of postassault contact between the survivor and offender and
      completed measures of the strength of their justice motive and their endorsement
      of sexual assault myths. Results indicated that participants ( N = 419) who held
      a strong justice motive showed higher endorsement of sexual assault myths.
      Participants were also more likely to endorse sexual assault myths when there was
      postoffense contact between the survivor and offender. The implications of these
      findings and their relevance to the criminal justice system are discussed,
      including the need for further research into the creation of survivor-oriented
      education and training capable of counteracting bias toward survivors of sexual
      violence and producing sustained attitudinal changes.

PMID- 30303036
TI  - Recommendations for cognitive screening and management in multiple sclerosis
      care.
AB  - PURPOSE:: To promote understanding of cognitive impairment in multiple sclerosis
      (MS), recommend optimal screening, monitoring, and treatment strategies, and
      address barriers to optimal management. METHODS:: The National MS Society
      ("Society") convened experts in cognitive dysfunction (clinicians, researchers,
      and lay people with MS) to review the published literature, reach consensus on
      optimal strategies for screening, monitoring, and treating cognitive changes, and
      propose strategies to address barriers to optimal care. RECOMMENDATIONS:: Based
      on current evidence, the Society makes the following recommendations, endorsed by
      the Consortium of Multiple Sclerosis Centers and the International Multiple
      Sclerosis Cognition Society: Increased professional and patient
      awareness/education about the prevalence, impact, and appropriate management of
      cognitive symptoms. For adults and children (8+ years of age) with clinical or
      magnetic resonance imaging (MRI) evidence of neurologic damage consistent with
      MS: As a minimum, early baseline screening with the Symbol Digit Modalities Test
      (SDMT) or similarly validated test, when the patient is clinically stable; Annual
      re-assessment with the same instrument, or more often as needed to (1) detect
      acute disease activity; (2) assess for treatment effects (e.g. starting/changing
      a disease-modifying therapy) or for relapse recovery; (3) evaluate progression of
      cognitive impairment; and/or (4) screen for new-onset cognitive problems. For
      adults (18+ years): more comprehensive assessment for anyone who tests positive
      on initial cognitive screening or demonstrates significant cognitive decline,
      especially if there are concerns about comorbidities or the individual is
      applying for disability due to cognitive impairment. For children (<18 years):
      neuropsychological evaluation for any unexplained change in school functioning
      (academic or behavioral). Remedial interventions/accommodations for adults and
      children to improve functioning at home, work, or school.

PMID- 30303037
TI  - Age is a critical determinant in recovery from multiple sclerosis relapses.
AB  - OBJECTIVE: To evaluate the impact of age on recovery from multiple sclerosis
      relapses. BACKGROUND: Increasing disability in multiple sclerosis is a
      consequence of progressive disease and incomplete relapse recovery. METHODS: The
      first and last-ever relapse data (357 relapses in 193 patients) from the Olmsted
      County population-based multiple sclerosis cohort were systematically reviewed
      for age, fulminance, location (optic nerve, brainstem/cerebellar, spinal cord),
      peak deficit, and maximum recovery. Three different relapse-outcome measures were
      studied both as paired analyses and as an overall group effect: change from peak
      deficit to maximum recovery in raw functional system score related to the relapse
      (DeltaFSS), a previously published FSS-based relapse-impact model, and change
      from peak deficit to maximum recovery in Extended Disability Status Scale
      (DeltaEDSS) score. RESULTS: Older age was linearly associated with worse recovery
      in the DeltaFSS outcome ( p = 0.002), DeltaEDSS outcome ( p < 0.001), and the FSS
      based relapse-impact model ( p < 0.001). A multivariate analysis of DeltaFSS
      outcome linked poor recovery to older age ( p = 0.015), relapse location
      (transverse myelitis or brainstem/cerebellar syndrome; p < 0.001), and relapse
      fulminance ( p = 0.004). CONCLUSION: Multiple sclerosis-relapse recovery declines
      in a linear fashion with increased age, which should be considered when making
      treatment decisions.

PMID- 30303039
TI  - Precarious work and the risk of receiving a disability pension.
AB  - AIMS: Precarious employment is an emerging determinant of occupational health,
      but its association with work-related disability remains little understood. We
      operationalised precarious work as a multidimensional construct and examined how
      the accumulation of precarious job features predicts the incidence of receiving a
      disability pension (DP). METHODS: The study comprised 13,228 employees aged 20-54
      who had been interviewed for the Finnish Quality of Work Life Surveys in 1984,
      1990, 1997, or 2003. We measured precarious work with five variables that reflect
      both subjective and objective job insecurity: the threat of
      dismissal/unemployment; poor employability; low earnings; previous unemployment;
      and temporary contract. An eight-year follow-up was merged with the pooled cross
      sectional data, and Cox proportional hazard ratios (HR) for receiving a DP were
      compared between the insecurity measures, controlling for sociodemographic
      covariates, job characteristics and health at the baseline with a step-wise
      procedure. RESULTS: Precarious employees had an elevated risk of receiving a DP
      (all covariates adjusted for). The risk of receiving a DP was associated with
      subjective job insecurity, with the strongest indicator being poor employability.
      The association between the threat of unemployment and receiving a DP was weak
      before controlling for health. Among objective insecurity measures, low earnings
      and earlier unemployment were weakly connected to receiving a DP before
      controlling for sociodemographic covariates, job characteristics and health.
      CONCLUSIONS: We recommend the evaluation of several precarious job features in
      future studies. The risk of receiving a DP could potentially be offset by
      improving individuals' employability.

PMID- 30303038
TI  - Investigating the Effects of Tactile Masking and Surface Texture on the Velvet
      Hand Illusion.
AB  - When we hold thin metallic bars between the palms of our hands and rub the palms
      against each other, the feeling of touching smooth velvet occurs. Previous
      studies have shown that tactile motion and pressure on the palms are important
      for this velvet hand illusion. Interestingly, when we experience this illusion,
      we cannot feel the texture of our palms as we usually do. In the present study,
      we investigated the possibility that tactile masking contributes to the
      occurrence of the velvet hand illusion. We measured vibrotactile detection
      performance on the palms of the hands during the occurrence of the velvet hand
      illusion. The detection performance was worse when the illusion occurred than
      when it did not. Moreover, the degradation of the detection performance
      correlated positively with the subjective magnitude of the illusion. We also
      examined whether additional surface texture could affect the occurrence of the
      illusion and found that the illusion became weaker as the roughness of the
      surface increased. These findings suggest that tactile motion and pressure
      information delivered by the bars of smooth surface mask tactile sensations on
      the palms of the hands, resulting in an illusory smooth, frictionless feeling on
      the palms.

PMID- 30303040
TI  - Electrochemically generated bimetallic reductive mediator Cu1+[Ni2+(CN)4]1- for
      the degradation of CF4 to ethanol by electro-scrubbing.
AB  - Remediation of electronic gas CF4 using commercially available technologies
      results in another kind of greenhouse gas and corrosive side products. This
      investigation aimed to develop CF4 removal at room temperature with formation of
      useful product by attempting an electrogenerated Cu1+[Ni2+(CN)4]1- mediator. The
      initial electrolysis of the bimetallic complex at the anodized Ti cathode
      demonstrated Cu1+[Ni2+(CN)4]1- formation, which was confirmed by additional
      electron spin resonance results. The degradation of CF4 followed mediated
      electrochemical reduction by electrogenerated Cu1+[Ni2+(CN)4]1-. The removal
      efficiency of CF4 of 95% was achieved by this electroscrubbing process at room
      temperature. The spectral results of online and offline Fourier transform
      infrared analyzer, either in gas or in solution phase, demonstrated that the
      product formed during the removal of CF4 by electrogenerated Cu1+[Ni2+(CN)4]1- by
      electroscrubbing was ethanol (CH3CH2OH), with a small amount of trifluoroethane
      (CF3CH3) intermediate.

PMID- 30303041
TI  - Relationship between genetic polymorphism of MTHFR C677T and lower extremities
      deep venous thrombosis.
AB  - OBJECTIVE: To investigate the association between the polymorphism of
      methylenetetrahydrofolate reductase (MTHFR) gene and the formation of lower
      extremities deep venous thrombosis, and to evaluate the etiology of deep venous
      thrombosis. METHODS: Polymorphisms of the 677th site C/T in MTHFR gene for 101
      patients with lower extremities deep venous thrombosis (DVT group) and 120
      healthy subjects (control group) were detected by polymerase chain reaction with
      sequence-specific primers. Genotype and allelic frequencies were compared between
      the two groups. RESULTS: Genotype frequencies of CC, CT and TT in MTHFR C677 T
      were 41.58, 25.74 and 32.67% in DVT group, and 58.33, 23.33 and 18.33% in control
      group, respectively. There was a significant difference in TT genotype frequency
      between the two groups (P <0.05). CONCLUSION: The frequency of MTHFR 677TT
      genotype may be correlated with the morbility of DVT.

PMID- 30303042
TI  - Workplace Heat Exposure Management in Indian Construction Workers Using Cooling
      Garment.
AB  - Construction workers are at high risk of heat-related illnesses during summer
      months in India. The personal cooling garment (PCG) is a microclimate assistive
      device that provides protection from heat stress. The applicability and efficacy
      of wearing PCG for the physiological and subjective responses were tested on 29
      healthy construction workers at actual field worksites. During the test, the
      climatic conditions were 103.64 +/- 38.3 degrees F dry bulb temperature, 41.2 +/-
      13.4% relative humidity, and wet bulb globe temperature 91.43 +/- 39.92 degrees
      F. Mean weighted skin temperature was significantly lowered by 38.66 +/- 33.98
      degrees F when wearing PCG as compared with wearing habitual clothing (HC), 32.36
      +/- 33.44 degrees F ( p < .05). Mean sweat loss was also significantly lower when
      wearing PCG: 0.365 +/- 0.257 kg as compared with wearing HC: 0.658 +/- 0.342 kg (
      p < .05). Heart rate, along with back and chest skin temperatures were
      significantly reduced with wearing PCG. The present study suggests that PCG
      provides an affordable way of alleviating the discomfort and physiological strain
      caused by environmental heat exposure.

PMID- 30303043
TI  - Safety, long-term outcomes and predictors of recurrence following a single
      catheter ablation procedure for atrial fibrillation.
AB  - BACKGROUND: Data regarding long-term outcomes of atrial fibrillation (AF)
      catheter ablation are limited. This study evaluated the safety, long-term
      efficacy and predictors of recurrence after a single left atrial ablation
      procedure in patients with paroxysmal (PAF) and non-paroxysmal AF (NPAF).
      METHODS: Data from 520 patients (354 males, mean age 57.08 +/- 11.33 years) with
      PAF (n = 356, 68.5%) or NPAF (n = 164, 31.5%) who underwent a single
      radiofrequency ablation procedure were analysed. Across the NPAF group, there
      were 143 (27.5%) patients with persistent AF and 21 (4%) with long-standing
      persistent AF. The mean follow-up period was 39.05 +/- 20.83 months (range 19-60
      months). RESULTS: Arrhythmia recurrence was observed in 102/356 (28.7%) of PAF
      patients and in 63/164 (38.4%) of NPAF patients. In patient with PAF, sinus
      rhythm maintenance was observed in 76.9%, 73% and 71.3% of patients at 1, 2 and 5
      years of follow-up, respectively. In patients with NPAF, sinus rhythm was
      maintained in 68.7%, 63.4% and 61.6% of patients at 1, 2 and 5 years of follow
      up, respectively. Independent predictors of AF recurrence were left atrial
      diameter (OR 1.15, 95% CI 1.10-1.21, p < 0.01) as well as early arrhythmia
      recurrence during the blanking period of 3 months after the procedure (OR 8.13,
      95% CI 5.10-12.82, p < 0.01). Major complications were observed in 11 patients
      (2.1%). CONCLUSIONS: Long-term arrhythmia-free survival rates remain high among
      PAF and NPAF patients after a single catheter ablation procedure. Left atrial
      diameter and early arrhythmia recurrence were independent predictors of late
      arrhythmia recurrence in both PAF and NPAF patients.

PMID- 30303045
TI  - Letter to the Editor Regarding "The Relationship of Welding Fume Exposure,
      Smoking, and Pulmonary Function in Welders".

PMID- 30303044
TI  - Inclusion of intimate partner violence-related content within undergraduate
      health care professional curriculum: mixed methods study of academics' attitudes
      and beliefs.
AB  - BACKGROUND: Undergraduate preparation is important in ensuring health care
      professionals are prepared to identify and respond to intimate partner violence
      (IPV). Previous studies confirm this education is highly variable and IPV-related
      content remains marginalised in undergraduate nursing, midwifery and paramedicine
      curricula. AIM: To investigate frontline academics' attitudes and beliefs in
      relation to the inclusion of IPV-related content in the aforementioned degrees.
      DESIGN: A large multi-phase mixed methods Australian case study of Australian
      undergraduate nursing, midwifery and paramedicine degrees. In this paper,
      components of the survey and interviews from this study will be reported on.
      METHODS: Quantitative comparative analysis of a 51-item on-line survey and
      qualitative thematic analysis of guided conversational interviews. RESULTS:
      Across Australian universities IPV remains poorly embedded in nursing, midwifery
      and paramedicine programmes. Academics report a range of barriers to such
      inclusion, including an already overcrowded curriculum, a lack of confident and
      competent academics to teach this content area and a lack of support for this
      content inclusion. One factor statistically significant in its association with
      non-inclusion of IPV-related content was academic attitudes of professional role
      resistance. Gender was also identified as a significant factor associated with
      non-inclusion and resistant professional attitudes. Qualitative interviews
      revealed that only six of the 18 participants identified IPV-related care as
      within their scope of practice, with professional role resistance a common theme
      identified. CONCLUSION: Though professional organisation and policy makers now
      advocate for the inclusion of IPV-related content in the undergraduate
      preparation of nurses and midwives, work remains to address gendered and
      resistant attitudes amongst academics.

PMID- 30303046
TI  - Polyphenols as New Leads in Drug Discovery: Biological Activity and Mechanisms.

PMID- 30303047
TI  - Advances in Usage of Venom Proteins as Diagnostics and Therapeutic Mediators.

PMID- 30303048
TI  - Culturing practices and the care of the urinary catheter in reducing NHSN-defined
      catheter-associated urinary tract infections: The tale of two teaching hospitals.
AB  - We compared interventions to improve urinary catheter care and urine culturing in
      adult intensive care units of 2 teaching hospitals. Compared to hospital A,
      hospital B had lower catheter utilization, more compliance with appropriate
      indications and maintenance, but higher urine culture use and more positive urine
      cultures per 1,000 patient days.

PMID- 30303049
TI  - SCAN: A novel approach for vancomycin time-out.

PMID- 30303050
TI  - A retrospective, population-based cohort study of driving under the influence,
      Alzheimer's disease diagnosis, and survival.
AB  - : ABSTRACTIntroduction:The relationship between Alzheimer's Disease (AD) and
      alcohol addiction is poorly characterized. Arrests for driving under the
      influence (DUI) can serve as a proxy for alcohol addiction. Therefore, the
      potential association between DUI and AD could be helpful in understanding the
      relationship between alcohol abuse and AD. MATERIALS AND METHODS: A
      retrospective, population-based cohort study using state health and law
      enforcement data was performed. The study cross-referenced 141,281 South Carolina
      Alzheimer's Disease Registry cases with state law enforcement data. RESULTS: Of
      the 2,882 registry cases (1.4%) found to have a history of at least one DUI
      arrest, cases were predominantly White (58.7%) and male (77.4%). Results showed a
      correlation coefficient of 0.7 (p < 0.0001) between the age of first DUI arrest
      and the age of AD diagnosis. A dose-response relationship between the number of
      DUIs and age of AD onset was found to exist, where those with a history of DUI
      arrest were diagnosed an average of 9.1 years earlier, with a further 1.8 years
      earlier age at diagnosis in those with two or more arrests for DUI. A history of
      DUI arrest was also found to be negatively associated with survival after
      diagnosis, with a 10% decreased life expectancy in those with a DUI arrest
      history. CONCLUSIONS: Driving under the influence, a potential indicator of
      alcohol addiction, is associated with an earlier onset of AD registry diagnosis
      and shortened survival after diagnosis. This study contributes to the growing
      body of evidence suggesting that some cases of AD are alcohol related and,
      possibly, postponable or preventable.

PMID- 30303051
TI  - Evaluating Mild Cognitive Impairment in Essential Tremor: How Many and Which
      Neuropsychological Tests?
AB  - OBJECTIVES: Essential tremor (ET) confers an increased risk for developing both
      amnestic and non-amnestic mild cognitive impairment (MCI). Yet, the optimal
      measures for detecting mild cognitive changes in individuals with this movement
      disorder have not been established. We sought to identify the cognitive domains
      and specific motor-free neuropsychological tests that are most sensitive to mild
      deficits in cognition as defined by a Clinical Dementia Rating (CDR) of 0.5,
      which is generally associated with a clinical diagnosis of MCI. METHODS: A total
      of 196 ET subjects enrolled in a prospective, longitudinal, clinical-pathological
      study underwent an extensive motor-free neuropsychological test battery and were
      assigned a CDR score. Logistic regression analyses were performed to identify the
      neuropsychological tests which best identified individuals with CDR of 0.5 (mild
      deficits in cognition) versus 0 (normal cognition). RESULTS: In regression
      models, we identified five tests in the domains of Memory and Executive Function
      which best discriminated subjects with CDR of 0.5 versus 0 (86.9% model
      classification accuracy). These tests were the California Verbal Learning Test II
      Total Recall, Logical Memory II, Verbal-Paired Associates I, Category Switching
      Fluency, and Color-Word Inhibition. CONCLUSIONS: Mild cognitive difficulty among
      ET subjects is best predicted by combined performance on five measures of memory
      and executive function. These results inform the nature of cognitive dysfunction
      in ET and the creation of a brief cognitive battery to assess patients with ET
      for cognitively driven dysfunction in life that could indicate the presence of
      MCI. (JINS, 2018, 24, 1084-1098).

PMID- 30303052
TI  - Three-dimensional printed degradable splint in the treatment of pulmonary artery
      sling associated with severe bilateral bronchus stenosis.
AB  - Pulmonary artery sling is a congenital cardiovascular disease and is usually
      accompanied by tracheobronchial stenosis. Generally, infants diagnosed with
      pulmonary artery sling should have surgery. However, the treatment of
      tracheobronchial stenosis is still controversial. Our team developed a
      customised, degradable, three-dimensional printed splint and successfully applied
      it in the treatment of pulmonary artery sling associated with severe bilateral
      bronchus stenosis. We suggested that three-dimensional printing may be a novel
      and effective way to treat tracheobronchial stenosis and other diseases in
      children.

PMID- 30303053
TI  - Description of Ore Particles from X-Ray Microtomography (XMT) Images, Supported
      by Scanning Electron Microscope (SEM)-Based Image Analysis.
AB  - In this paper, three-dimensional (3D) image data of ore particle systems is
      investigated. By combining X-ray microtomography with scanning electron
      microscope (SEM)-based image analysis, additional information about the
      mineralogical composition from certain planar sections can be gained. For the
      analysis of tomographic images of particle systems the extraction of single
      particles is essential. This is performed with a marker-based watershed algorithm
      and a post-processing step utilizing a neural network to reduce oversegmentation.
      The results are validated by comparing the 3D particle-wise segmentation
      empirically with 2D SEM images, which have been obtained with a different imaging
      process and segmentation algorithm. Finally, a stereological application is
      shown, in which planar SEM images are embedded into the tomographic 3D image.
      This allows the estimation of local X-ray attenuation coefficients, which are
      material-specific quantities, in the entire tomographic image.

PMID- 30303054
TI  - WWGD (What would Gwyneth do?).

PMID- 30303055
TI  - Understanding changes in the standardized antimicrobial administration ratio for
      total antimicrobial use after implementation of prospective audit and feedback.
AB  - In this single-center study, the standardized antimicrobial administration ratio
      (SAAR) for total antimicrobial use decreased in response to a stewardship
      intervention. Antimicrobial prescribing and clinical outcomes were stable or
      improved during the period of lower SAARs. Our findings suggest that SAAR values
      of ~0.8 can be safely achieved.

PMID- 30303056
TI  - Clinical, personality, and neurodevelopmental phenotypes in borderline
      personality disorder: a family study.
AB  - BACKGROUND: Borderline personality disorder (BPD) is characterized by a
      heterogeneous clinical phenotype that emerges from interactions among genetic,
      biological, neurodevelopmental, and psychosocial factors. In the present family
      study, we evaluated the familial aggregation of key clinical, personality, and
      neurodevelopmental phenotypes in probands with BPD (n = 103), first-degree
      biological relatives (n = 74; 43% without a history of psychiatric disorder), and
      non-psychiatric controls (n = 99). METHODS: Participants were assessed on DSM-IV
      psychiatric diagnoses, symptom dimensions of emotion dysregulation and
      impulsivity, 'big five' personality traits, and neurodevelopmental
      characteristics, as part of a larger family study on neurocognitive, biological,
      and genetic markers in BPD. RESULTS: The most common psychiatric diagnoses in
      probands and relatives were major depression, substance use disorders, post
      traumatic stress disorder, anxiety disorders, and avoidant personality disorder.
      There was evidence of familial aggregation for specific dimensions of impulsivity
      and emotion dysregulation, and the big five traits neuroticism and
      conscientiousness. Both probands and relatives reported an elevated
      neurodevelopmental history of attentional and behavioral difficulties.
      CONCLUSIONS: These results support the validity of negative affectivity- and
      impulse-spectrum phenotypes associated with BPD and its familial risk. Further
      research is needed to investigate the aggregation of neurocognitive, neural and
      genetic factors in families with BPD and their associations with core phenotypes
      underlying the disorder.

PMID- 30303057
TI  - Analysis of spatial-temporal distribution and influencing factors of pulmonary
      tuberculosis in China, during 2008-2015.
AB  - At present, the number of people with tuberculosis in China is second only to
      India and ranks second in the world. Under such a severe case of tuberculosis in
      China, prevention and control of pulmonary tuberculosis are urgently needed. This
      study aimed to study the temporal and geographical relevance of the pathogenesis
      of pulmonary tuberculosis and the factors affecting the incidence of
      tuberculosis. Spatial autocorrelation model was used to study the spatial
      distribution characteristics of pulmonary tuberculosis from a quantitative level.
      The research results showed that the overall incidence of pulmonary tuberculosis
      (IPT) in China was low in the east, high in the west and had certain seasonal
      characteristics. We use Spatial Lag Model to explore influencing factors of
      pulmonary tuberculosis. It indicates that the IPT is high in areas with
      underdeveloped economics, poor social services and low average smoking ages.
      Additionally, the IPT is high in areas with high AIDS prevalence. Also, compared
      with Classical Regression Model and Spatial Error Model, our model has smaller
      values of Akaike information criterion and Schwarz criterion. Besides, our model
      has bigger values of coefficient of determination (R2) and log-likelihood (log L)
      than the other two models. Apart from that, it is more significant than Spatial
      Error Models in the spatial dependence test for the IPT.

PMID- 30303058
TI  - Integrative review: Persistent vocalizations among nursing home residents with
      dementia.
AB  - : ABSTRACTBackground:Nursing home (NH) residents with dementia commonly exhibit
      persistent vocalizations (PVs), otherwise known in the literature as disruptive
      or problematic vocalizations. Having a better understanding of PVs and the
      research completed to date on this phenomenon is important to guide further
      research and clinical practice in NHs. This integrative review examines the
      current literature on the phenomenon of PVs among NH residents with dementia.
      METHODS: We conducted a search in the PubMed, Scopus, Ovid Medline, and CINAHL
      databases for articles published in English. Articles were included if the focus
      was specifically on research involving vocal behaviors of older adults with
      dementia residing in NHs. RESULTS: Our literature search revealed eight research
      articles that met the inclusion criteria. These studies were published in 2011 or
      earlier and involved small sample sizes. Seven of these studies were descriptive
      and the eighth was a non-pharmacological intervention study for PVs exhibited by
      NH residents with dementia. These studies were vastly different in their
      labeling, definitions, and categorization of the PVs as well as methods of
      measuring PVs. CONCLUSION: The heterogeneity of the evidence limits the ability
      to make recommendations for practice. Given the paucity of research on this
      phenomenon; recommendations for additional research are given.

PMID- 30303060
TI  - Utilizing the electronic health record to construct antibiograms for previously
      healthy children with urinary tract infections.
AB  - Traditional antibiograms can guide empiric antibiotic therapy, but they may miss
      differences in resistance across patient subpopulations. In this retrospective
      descriptive study, we constructed and validated antibiograms using International
      Classification of Disease, Tenth Revision (ICD-10) codes and other discrete data
      elements to define a cohort of previously healthy children with urinary tract
      infections. Our results demonstrate increased antibiotic susceptibility. This
      methodology may be modified to create other syndrome-specific antibiograms.

PMID- 30303059
TI  - The characteristics of psychotic features in bipolar disorder.
AB  - BACKGROUND: In a large and comprehensively assessed sample of patients with
      bipolar disorder type I (BDI), we investigated the prevalence of psychotic
      features and their relationship with life course, demographic, clinical, and
      cognitive characteristics. We hypothesized that groups of psychotic symptoms
      (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations)
      have distinct relations to risk factors. METHODS: In a cross-sectional study of
      1342 BDI patients, comprehensive demographical and clinical characteristics were
      assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview.
      In addition, levels of childhood maltreatment and intelligence quotient (IQ) were
      assessed. The relationships between these characteristics and psychotic symptoms
      were analyzed using multiple general linear models. RESULTS: A lifetime history
      of psychotic symptoms was present in 73.8% of BDI patients and included delusions
      in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic
      symptoms showed a significant younger age of disease onset (beta = -0.09, t = 
      3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F11
      338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with
      hallucinations had significant higher levels of childhood maltreatment (beta =
      0.09, t = 3.04, p = 0.002). CONCLUSIONS: In this large cohort of BDI patients,
      the vast majority of patients had experienced psychotic symptoms. Psychotic
      symptoms in BDI were associated with an earlier disease onset and more frequent
      hospitalizations particularly for manic episodes. The study emphasizes the
      strength of the relation between childhood maltreatment and hallucinations but
      did not identify distinct subgroups based on psychotic features and instead
      reported of a large heterogeneity of psychotic symptoms in BD.

PMID- 30303061
TI  - Dialectical behaviour therapy v. mentalisation-based therapy for borderline
      personality disorder.
AB  - BACKGROUND: Dialectical behaviour therapy (DBT) and mentalisation-based therapy
      (MBT) are both widely used evidence-based treatments for borderline personality
      disorder (BPD), yet a head-to-head comparison of outcomes has never been
      conducted. The present study therefore aimed to compare the clinical outcomes of
      DBT v. MBT in patients with BPD. METHODS: A non-randomised comparison of clinical
      outcomes in N = 90 patients with BPD receiving either DBT or MBT over a 12-month
      period. RESULTS: After adjusting for potentially confounding differences between
      participants, participants receiving DBT reported a significantly steeper decline
      over time in incidents of self-harm (adjusted IRR = 0.93, 95% CI 0.87-0.99, p =
      0.02) and in emotional dysregulation (adjusted beta = -1.94, 95% CI -3.37 to 
      0.51, p < 0.01) than participants receiving MBT. Differences in treatment dropout
      and use of crisis services were no longer significant after adjusting for
      confounding, and there were no significant differences in BPD symptoms or
      interpersonal problems. CONCLUSIONS: Within this sample of people using
      specialist personality disorder treatment services, reductions in self-harm and
      improvements in emotional regulation at 12 months were greater amongst those
      receiving DBT than amongst those receiving MBT. Experimental studies assessing
      outcomes beyond 12 months are needed to examine whether these findings represent
      differences in the clinical effectiveness of these therapies.

PMID- 30303062
TI  - Paediatric pulmonary hypertension caused by an ACVRL1 mutation presenting as
      Ortner syndrome.
AB  - We report a rare aetiology of vocal cord paralysis secondary to undiagnosed
      severe pulmonary hypertension from a de novo ACVRL1 variant identified by whole
      genome sequencing. The patient had a partial response to intravenous treprostinil
      in addition to inhaled nitric oxide, bosentan, and sildenafil.

PMID- 30303063
TI  - Maternal antenatal mood and child development: an exploratory study of treatment
      effects on child outcomes up to 5 years.
AB  - Effective treatment of maternal antenatal depression may ameliorate adverse
      neurodevelopmental outcomes in offspring. We performed two follow-up rounds of
      children at age 2 and age 5 whose mothers had received either specialized
      cognitive-behavioural therapy or routine care for depression while pregnant. Of
      the original cohort of 54 women, renewed consent was given by 28 women for 2-year
      follow-up and by 24 women for 5-year follow-up. Child assessments at the 2-year
      follow-up included the Parenting Stress Index (PSI), Bayley Scales of Infant
      Development (BSID-III) and the Child Behaviour Checklist (CBCL). The 5-year
      follow-up included the Wechsler Preschool and Primary Scales of Intelligence
      (WPPSI-III) and again the CBCL. Treatment during pregnancy showed significant
      benefits for children's development at age 2, but not at age 5. At 2 years,
      intervention effects were found with lower scores on the PSI Total score, Parent
      Domain and Child domain (d=1.44, 1.47, 0.96 respectively). A non-significant
      trend favoured the intervention group on most subscales of the CBCL and the BSID
      III (most notably motor development: d =0.52). In contrast, at 5-year follow-up,
      no intervention effects were found. Also, irrespective of treatment allocation,
      higher depression or anxiety during pregnancy was associated with higher CBCL and
      lower WPPSI-III scores at 5 years. This is one of the first controlled studies to
      evaluate the long-term effect of antenatal depression treatment on infant
      neurodevelopmental outcomes, showing some benefit. Nevertheless, caution should
      be taken interpreting the results because of a small sample size, and larger
      studies are warranted.

PMID- 30303064
TI  - Written progress tests in postgraduate psychiatry.

PMID- 30303065
TI  - Depressive symptoms in relation to clinical symptom onset of mild cognitive
      impairment.
AB  - : ABSTRACTObjective:There is increasing evidence of an association between
      depressive symptoms and mild cognitive impairment (MCI) in cross-sectional
      studies, but the longitudinal association between depressive symptoms and risk of
      MCI onset is less clear. The authors investigated whether baseline symptom
      severity of depression was predictive of time to onset of symptoms of MCI.
      METHOD: These analyses included 300 participants from the BIOCARD study, a cohort
      of individuals who were cognitively normal at baseline (mean age = 57.4 years)
      and followed for up to 20 years (mean follow-up = 2.5 years). Depression symptom
      severity was measured using the Hamilton Depression Scale (HAM-D). The authors
      assessed the association between dichotomous and continuous HAM-D and time to
      onset of MCI within 7 years versus after 7 years from baseline (reflecting the
      mean time from baseline to onset of clinical symptoms in the cohort) using Cox
      regression models adjusted for gender, age, and education. RESULTS: At baseline,
      subjects had a mean HAM-D score of 2.2 (SD = 2.8). Higher baseline HAM-D scores
      were associated with an increased risk of progression from normal cognition to
      clinical symptom onset <= 7 years from baseline (p = 0.043), but not with
      progression > 7 years from baseline (p = 0.194). These findings remained
      significant after adjustment for baseline cognition. CONCLUSIONS: These results
      suggest that low levels of depressive symptoms may be predictive of clinical
      symptom onset within approximately 7 years among cognitively normal individuals
      and may be useful in identifying persons at risk for MCI due to Alzheimer's
      disease.

PMID- 30303067
TI  - The case for investing in WHO.

PMID- 30303068
TI  - Age-related macular degeneration: treatment at what cost?

PMID- 30303066
TI  - Adrb2 controls glucose homeostasis by developmental regulation of pancreatic
      islet vasculature.
AB  - A better understanding of processes controlling the development and function of
      pancreatic islets is critical for diabetes prevention and treatment. Here, we
      reveal a previously unappreciated function for pancreatic beta2-adrenergic
      receptors (Adrb2) in controlling glucose homeostasis by restricting islet
      vascular growth during development. Pancreas-specific deletion of Adrb2 results
      in glucose intolerance and impaired insulin secretion in mice, and unexpectedly,
      specifically in females. The metabolic phenotypes were recapitulated by Adrb2
      deletion from neonatal, but not adult, beta-cells. Mechanistically, Adrb2 loss
      increases production of Vascular Endothelial Growth Factor-A (VEGF-A) in female
      neonatal beta-cells and results in hyper-vascularized islets during development,
      which in turn, disrupts insulin production and exocytosis. Neonatal correction of
      islet hyper-vascularization, via VEGF-A receptor blockade, fully rescues
      functional deficits in glucose homeostasis in adult mutant mice. These findings
      uncover a regulatory pathway that functions in a sex-specific manner to control
      glucose metabolism by restraining excessive vascular growth during islet
      development.

PMID- 30303069
TI  - Standing by France's social contract: Macron's health reform.

PMID- 30303070
TI  - Offline: It's time to hold the private sector accountable.

PMID- 30303071
TI  - Brexit, health care, and life sciences: plan for the worst.

PMID- 30303072
TI  - The Cochrane board votes to expel Peter Gotzsche.

PMID- 30303074
TI  - Inhaled triple therapy in chronic obstructive pulmonary disease.

PMID- 30303073
TI  - Cautery in medieval surgery: a unique palaeopathological case.

PMID- 30303075
TI  - Inhaled triple therapy in chronic obstructive pulmonary disease.

PMID- 30303076
TI  - Inhaled triple therapy in chronic obstructive pulmonary disease.

PMID- 30303077
TI  - Inhaled triple therapy in chronic obstructive pulmonary disease - Authors' reply.

PMID- 30303078
TI  - Free to breathe hard in the Tour de France.

PMID- 30303079
TI  - Canine rabies vaccination reduces child rabies cases in Malawi.

PMID- 30303080
TI  - Involvement of doctors in Aum Shinrikyo.

PMID- 30303081
TI  - Department of Error.

PMID- 30303082
TI  - Department of Error.

PMID- 30303083
TI  - Age-related macular degeneration.
AB  - Age-related macular degeneration is a leading cause of visual impairment and
      severe vision loss. Clinically, it is classified as early-stage (medium-sized
      drusen and retinal pigmentary changes) to late-stage (neovascular and atrophic).
      Age-related macular degeneration is a multifactorial disorder, with dysregulation
      in the complement, lipid, angiogenic, inflammatory, and extracellular matrix
      pathways implicated in its pathogenesis. More than 50 genetic susceptibility loci
      have been identified, of which the most important are in the CFH and ARMS2 genes.
      The major non-genetic risk factors are smoking and low dietary intake of
      antioxidants (zinc and carotenoids). Progression from early-stage to late-stage
      disease can be slowed with high-dose zinc and antioxidant vitamin supplements.
      Intravitreal anti-vascular endothelial growth factor therapy (eg, ranibizumab,
      aflibercept, or bevacizumab) is highly effective at treating neovascular age
      related macular degeneration, and has markedly decreased the prevalence of visual
      impairment in populations worldwide. Currently, no proven therapies for atrophic
      disease are available, but several agents are being investigated in clinical
      trials. Future progress is likely to be from improved efforts in prevention and
      risk-factor modification, personalised medicine targeting specific pathways,
      newer anti-vascular endothelial growth factor agents or other agents, and
      regenerative therapies.

PMID- 30303084
TI  - US Preventive Services Task Force recommendation statement regarding screening
      for peripheral artery disease with the ankle-brachial index: deja vu all over
      again.

PMID- 30303085
TI  - Inside Zimbabwe's efforts to tame cholera.

PMID- 30303086
TI  - Bleeding interaction between fluconazole and warfarin.

PMID- 30303087
TI  - Predictive pathology of lung cancer immunotherapy response.

PMID- 30303088
TI  - Understanding irrationality: the key to changing behaviours and improving
      management of respiratory diseases?

PMID- 30303089
TI  - Tobacco control, lung cancer, and tuberculosis in Singapore.

PMID- 30303090
TI  - Peter Czanyo: lung cancer survivor.

PMID- 30303091
TI  - Negative trials in critical care medicine and the hurdles.

PMID- 30303092
TI  - Corrections.

PMID- 30303093
TI  - Ending cholera for all.

PMID- 30303094
TI  - Point-of-care tests for chlamydia and gonorrhoea in Indigenous communities.

PMID- 30303095
TI  - Measles: is a new vaccine approach needed?

PMID- 30303096
TI  - Antibiotic stewardship in aged care facilities.

PMID- 30303097
TI  - Availability of essential diagnostics in primary care in India.

PMID- 30303098
TI  - Antibiotic prophylaxis approaches for urinary tract infections.

PMID- 30303099
TI  - Pakistan's national action plan for antimicrobial resistance: translating ideas
      into reality.

PMID- 30303100
TI  - Ethanol lock for CLABSI in children with cancer: a matter of (dwell) time?

PMID- 30303101
TI  - Scabies control: the forgotten role of personal hygiene - Authors' reply.

PMID- 30303102
TI  - Scabies control: the forgotten role of personal hygiene.

PMID- 30303103
TI  - Measles in Europe.

PMID- 30303105
TI  - Australia tackles HTLV-1.

PMID- 30303104
TI  - Polio returns to Papua New Guinea.

PMID- 30303109
TI  - Intracranial hypertension and vasculitic infarction in a patient with severe
      cerebral melioidosis.

PMID- 30303108
TI  - Molecular point-of-care testing for chlamydia and gonorrhoea in Indigenous
      Australians attending remote primary health services (TTANGO): a cluster
      randomised, controlled, crossover trial.
AB  - BACKGROUND: Timely diagnosis and treatment of sexually transmissible infections
      will prevent morbidity and onward transmission. We aimed to assess the efficacy
      of a point-of-care molecular test for Chlamydia trachomatis and Neisseria
      gonorrhoeae infections at the cluster level to improve infection management among
      Indigenous Australian communities with high prevalence of sexually transmissible
      infections. METHODS: In this cluster-randomised crossover study, we recruited
      primary health services in Western Australia, Far North Queensland, and South
      Australia that provide care to Indigenous people in regional or remote locations.
      The services were eligible if they did 150 or more tests for C trachomatis or N
      gonorrhoeae infection per year among individuals aged 16-29 years, and if C
      trachomatis or N gonorrhoeae positivity was 10% or higher. Services were randomly
      assigned (1:1) by use of a random-number generator, stratified by geographical
      region, to either standard care conditions with routine laboratory-based sexually
      transmissible infection testing for 12 months followed by 12 months of
      intervention with molecular point-of-care testing, or the reverse sequence. The
      primary outcome was the proportion of people (aged 16-29 years) found to have C
      trachomatis or N gonorrhoeae who had a positive result at retesting 3 weeks to 3
      months after treatment, and a secondary outcome was treatment within 7 days, both
      in those aged 16-29 years and at the cluster level. We did these analyses using
      data from all participants who had a positive result at testing, by point-of-care
      of laboratory testing (ie, the intention-to-treat population). The trial is
      registered with Australian and New Zealand Clinical Trials Registry
      (ACTRN12613000808741). FINDINGS: Between June 1, 2013, and Feb 29, 2016, 12
      health services were enrolled and randomly assigned to standard care followed by
      intervention (six) and the reverse sequence (six). After randomisation, one
      health service that was initially assigned to standard care was excluded because
      it no longer met the inclusion criteria. 455 individuals tested positive for C
      trachomatis or N gonorrhoeae infection in the intervention group, and 405 tested
      positive in the standard care group. In the intervention group, 12 (19%) of 63
      individuals retested had a positive test result, compared with nine (13%) of 67
      with positive retests in the standard care group (relative ratio [RR] 1.42, 95%
      CI 0.64-3.13; p=0.405), and 347 (76%) were treated within 7 days in the
      intervention group, compared with 191 (47%) in the standard care group (RR 1.66,
      1.41-1.93; p<0.0001). INTERPRETATION: Retesting rates were too low to draw
      conclusions on the effect of the intervention on repeat infections. Further
      research will be needed to determine whether point-of-care tests have an effect
      on reinfection rates, and the sustainability of using this technology. However,
      our findings show that time to treatment of C trachomatis or N gonorrhoeae
      infections in primary care clinics in remote areas in Australia with a high
      prevalence of sexually transmissible infections could be substantially reduced by
      the use of molecular point-of-care tests. FUNDING: The National Health and
      Medical Research Council, Australia.

PMID- 30303110
TI  - CAR T-cell therapy: perceived need versus actual evidence.

PMID- 30303111
TI  - The impact of Brexit on UK cancer research.

PMID- 30303112
TI  - Does GDPR harm or benefit research participants? An EORTC point of view.

PMID- 30303113
TI  - Long-term strategies for thyroid health monitoring after nuclear accidents:
      recommendations from an Expert Group convened by IARC.

PMID- 30303114
TI  - Follow-up surveillance of Wilms' tumour.

PMID- 30303115
TI  - Follow-up surveillance of Wilms' tumour.

PMID- 30303116
TI  - Follow-up surveillance of Wilm's tumour - Authors' reply.

PMID- 30303117
TI  - Maintenance PARP inhibitor therapy: is maintaining quality of life enough?

PMID- 30303118
TI  - Common analgesics and ovarian cancer prognosis.

PMID- 30303119
TI  - Common analgesics and ovarian cancer prognosis.

PMID- 30303120
TI  - Common analgesics and ovarian cancer prognosis - Authors' reply.

PMID- 30303122
TI  - Correction to Lancet Oncol 2018; 19: 1315-27.

PMID- 30303121
TI  - GDPR-not just an EU regulation?

PMID- 30303123
TI  - Correction to Lancet Oncol 2018; 19: e514.

PMID- 30303124
TI  - Correction to Lancet Oncol 2018; 19: 1155-56.

PMID- 30303125
TI  - Correction to Lancet Oncol 2015; 16: 1473-82.

PMID- 30303126
TI  - Opportunities and priorities for breast surgical research.
AB  - The 2013 Breast Cancer Campaign gap analysis established breast cancer research
      priorities without a specific focus on surgical research or the role of surgeons
      on breast cancer research. This Review aims to identify opportunities and
      priorities for research in breast surgery to complement the 2013 gap analysis. To
      identify these goals, research-active breast surgeons met and identified areas
      for breast surgery research that mapped to the patient pathway. Areas included
      diagnosis, neoadjuvant treatment, surgery, adjuvant therapy, and attention to
      special groups (eg, those receiving risk-reducing surgery). Section leads were
      identified based on research interests, with invited input from experts in
      specific areas, supported by consultation with members of the Association of
      Breast Surgery and Independent Cancer Patients' Voice groups. The document was
      iteratively modified until participants were satisfied that key priorities for
      surgical research were clear. Key research gaps included issues surrounding
      overdiagnosis and treatment; optimising treatment options and their selection for
      neoadjuvant therapies and subsequent surgery; reducing rates of re-operations for
      breast-conserving surgery; generating evidence for clinical effectiveness and
      cost-effectiveness of breast reconstruction, and mechanisms for assessing novel
      interventions; establishing optimal axillary management, especially post
      neoadjuvant treatment; and defining and standardising indications for risk
      reducing surgery. We propose strategies for resolving these knowledge gaps.
      Surgeons are ideally placed for a central role in breast cancer research and
      should foster a culture of engagement and participation in research to benefit
      patients and health-care systems. Development of infrastructure and surgical
      research capacity, together with appropriate allocation of research funding, is
      needed to successfully address the key clinical and translational research gaps
      that are highlighted in this Review within the next two decades.

PMID- 30303127
TI  - Use of modern imaging methods to facilitate trials of metastasis-directed therapy
      for oligometastatic disease in prostate cancer: a consensus recommendation from
      the EORTC Imaging Group.
AB  - Oligometastatic disease represents a clinical and anatomical manifestation
      between localised and polymetastatic disease. In prostate cancer, as with other
      cancers, recognition of oligometastatic disease enables focal, metastasis
      directed therapies. These therapies potentially shorten or postpone the use of
      systemic treatment and can delay further metastatic progression, thus increasing
      overall survival. Metastasis-directed therapies require imaging methods that
      definitively recognise oligometastatic disease to validate their efficacy and
      reliably monitor response, particularly so that morbidity associated with
      inappropriately treating disease subsequently recognised as polymetastatic can be
      avoided. In this Review, we assess imaging methods used to identify metastatic
      prostate cancer at first diagnosis, at biochemical recurrence, or at the
      castration-resistant stage. Standard imaging methods recommended by guidelines
      have insufficient diagnostic accuracy for reliably diagnosing oligometastatic
      disease. Modern imaging methods that use PET-CT with tumour-specific radiotracers
      (choline or prostate-specific membrane antigen ligand), and increasingly whole
      body MRI with diffusion-weighted imaging, allow earlier and more precise
      identification of metastases. The European Organisation for Research and
      Treatment of Cancer (EORTC) Imaging Group suggests clinical algorithms to
      integrate modern imaging methods into the care pathway at the various stages of
      prostate cancer to identify oligometastatic disease. The EORTC proposes clinical
      trials that use modern imaging methods to evaluate the benefits of metastasis
      directed therapies.

PMID- 30303128
TI  - Advancing shared decision making for symptom monitoring in people living beyond
      cancer.
AB  - Wellbeing after successful cancer treatment depends on more than merely reducing
      the risk of disease recurrence. Cancer survival can be characterised by
      uncertainty, fear, and the interpretation of bodily sensations as potentially
      symptomatic of cancer recurrence. This fear can lead to over-vigilance about
      bodily sensations and precautionary visits to the doctor, both of which can
      increase the chance of early detection but can also increase anxiety and decrease
      quality of life. In this Personal View, we consider the medical, psychological,
      and ethical issues related to the practice of self-directed symptom monitoring
      after completion of cancer treatment, focusing on the role of doctor-patient
      communication. We ask how clinicians can account for the plurality of values that
      patients might have when it comes to deciding on how to manage and respond to
      experiences of post-cancer symptoms. We advocate a shared decision-making
      approach that incorporates the assessment of an individual's cancer recurrence
      risks as well as psychosocial considerations regarding fear of cancer recurrence
      and mental health. We aim to raise awareness of the potential quality-of-life
      implications of symptom-monitoring practices, emphasising the need for a balance
      between physical and psychological health in people living beyond cancer.

PMID- 30303129
TI  - A vena caval mass: challenging diagnosis with a rare complication.

PMID- 30303131
TI  - From Editor's desk.

PMID- 30303132
TI  - Evaluation of CD4+ T-cells and CD8+ T-cells in triple-negative invasive breast
      cancer.

PMID- 30303130
TI  - Concurrent control of a brain-computer interface and natural overt movements.
AB  - OBJECTIVE: A primary control signal in brain-computer interfaces (BCIs) have been
      cortical signals related to movement. However, in cases where natural motor
      function remains, BCI control signals may interfere with other possibly
      simultaneous activity for useful ongoing movement. We sought to determine if the
      brain could learn to control both a BCI and concurrent overt movement execution
      in such cases. APPROACH: We designed experiments where BCI and overt movements
      must be used concurrently and in coordination to achieve a 2D centre out control.
      Power in the 70-90 Hz band of human electrocorticography (ECoG) signals, was used
      to generate BCI control commands for vertical movement of the cursor. These
      signals were deliberately recorded from the same human cortical site that
      produced the strongest movement related activity associated with the concurrent
      overt finger movements required for the horizontal movement of the cursor. MAIN
      RESULTS: We demonstrate that three subjects were able to perform the concurrent
      BCI task, controlling BCI and natural movements simultaneously and to a large
      extent independently. We conclude that the brain is capable of dissociating the
      original control signal dependency on movement, producing specific BCI control
      signals in the presence of motor related responses from the ongoing overt
      behaviour with which the BCI signal was initially correlated. SIGNIFICANCE: We
      demonstrate a novel human brain-computer interface (BCI) which can be used to
      control movement concurrently and in coordination with movements of the natural
      limbs. This demonstrates the dissociation of cortical activity from the behaviour
      with which it was originally associated despite the ongoing behaviour and shows
      the feasibility of achieving simultaneous BCI control of devices with natural
      movements.

PMID- 30303133
TI  - Expression of alpha-smooth muscle actin in benign and malignant salivary gland
      tumors: An immunohistochemical study.
AB  - Background and Objectives: Myoepithelial cells (ME) are known to contribute in
      the patterning of salivary gland neoplasms (SGN) and possess cytoplasmic smooth
      muscle actin (SMA) revealed by alpha SMA (alpha-SMA). The present study aimed to
      assess the expression of alpha-SMA in selected benign and malignant SGN
      (pleomorphic adenoma [PA], mucoepidermoid carcinoma (MEC), adenoid cystic
      carcinoma (ACC), and polymorphous low-grade adenocarcinoma (PLGA). Materials and
      Methods: The intensity and pattern of expression of alpha-SMA were studied in 25
      cases of SGN's ACC (n = 7), MEC (n = 8), PA (n = 8), and PLGA (n = 2), and
      correlated with the histological patterns. Results: Maximum expression of alpha
      SMA in the epithelial compartment was seen in ACC, followed by PA, whereas MEC
      and PLGA showed completely negative staining. The connective tissue expression
      was mild in ACC and MEC. The myxoid stroma of PA with "melting" pattern was
      weakly positive for alpha-SMA. The stroma in PLGA showed complete negativity. In
      ACC, alpha-SMA-positive cells were lining the cribriform spaces, small islands,
      and dispersed within large islands. Small nests showed complete positivity for
      alpha-SMA. Interpretation and Conclusion: In ACC, alpha-SMA expression supports
      the involvement of ME in epithelial organization explaining the histological
      patterns seen. In PA, the expression correlates with the predominantly secretory
      nature of ME. The absence of epithelial positivity in MEC and PLGA suggest that
      ME has less role to play in their histogenesis. The weak stromal positivity
      observed in MEC and ACC may be attributed to the positive immunoreactivity of
      myofibroblasts playing a role in modulating the course of SGN's.

PMID- 30303134
TI  - C-cell hyperplasia in sporadic and familial medullary thyroid carcinoma.
AB  - Context: C-cell hyperplasia (CCH) is characterized by increased mass of C-cells
      and has been identified as a precursor condition for medullary thyroid carcinoma
      (MTC). Varying proportion of MTCs is associated with CCH in different studies.
      This could be due to the lack of uniformity of the definitions and techniques
      used to identify CCH in these studies. Aims: This study aims to study the
      occurrence, clinicopathological, and immunohistochemical features of CCH in MTC
      diagnosed during a 22-year period at a tertiary care center in North India and to
      review the available literature on CCH. Materials and Methods: Eighty-seven
      consecutive cases of MTC were included in the study. Histological evaluation for
      the presence of CCH and neoplastic CCH was performed. Confirmation of CCH was
      done by immunohistochemistry for calcitonin and chromogranin. The presence of
      neoplastic CCH was correlated with clinical factors and prognostic factors.
      Results: Of 87 cases of MTC included in the study, 71 (82%) patients were
      sporadic and 16 (18%) had familial MTC. Neoplastic CCH was seen in 12 (75%)
      familial and in 9 (13%) sporadic MTC. Patients with familial MTC were more
      frequently associated with neoplastic CCH than sporadic MTC (P < 0.001), were
      younger (P < 0.001), and had more often bilateral and multifocal tumors (P <
      0.001). However, there was no significant difference in mean survival time and
      progression-free survival in patients with and without CCH. Conclusion: CCH,
      though more common in familial MTC, can also be seen in sporadic tumors. CCH is
      not associated with patient survival and disease progression.

PMID- 30303136
TI  - An autopsy based descriptive study of the spectrum of pulmonary lesions
      encountered in fetal deaths at a tertiary care center.
AB  - Background: : Fetal autopsy has been an indispensable tool in evaluating the
      cause of death. The most common cause for fetal deaths is associated with
      respiratory disorders accounting for around 60%. This study was undertaken to
      evaluate the gross and microscopic features of lungs in fetal autopsies and
      estimate the incidence of deaths attributable to pulmonary causes. Materials and
      Methods: : All fetuses received for autopsy at our institute were included in the
      study with prior consent. Gross and microscopic findings along with relevant
      clinical data were recorded. Results: A total of 426 autopsies were conducted
      from January 2011 to August 2016. Of those, 184 had abnormal pulmonary findings
      constituting 43.19%. Aspiration pneumonia was the most common finding with 67
      cases (36.4%), followed by atelectasis 54 cases (29.3%), congenital cystic
      adenomatoid malformation in 13 cases (7.1%), lung hypoplasia 12 cases (6.5%),
      pulmonary hemorrhage 21 (11.4%), 15 cases (8.15%) of hyaline membrane disease,
      one case (0.5%) of heterotaxy, and one case of extralobar pulmonary sequestration
      (0.5%). Congenital malformations of lungs were seen in 27 (14.67%) cases and 38
      cases (20.65%) had other associated anomalies. Conclusion: Pulmonary pathology is
      the most common finding in fetal deaths with aspiration pneumonitis being the
      most common avoidable cause. Accurate fetal autopsy along with clinical data are
      important in evaluating fetal deaths and can help in reduction of unexplained
      stillbirths.

PMID- 30303135
TI  - A prospective study of association of cancer stem cell marker aldehyde
      dehydrogenase 1 with clinicopathological profile in lung carcinoma patients.
AB  - Context: In India, lung carcinoma is the fifth-most common tumor and second-most
      common tumor in the males as per the Indian Council of Medical Research registry
      of 2002. It has been seen that ALDH1 expression in non-small cell lung cancer
      (NSCLC) and the presence of marker was linked to a more tumorigenic potential in
      the in vivo assessment and shorter disease-free survival in NSCLC patients with
      platinum treatment. Aims: Hence, our objective was to detect association of
      cancer stem cell (CSC) marker aldehyde dehydrogenase 1 (ALDH1) with
      clinicopathological profile in lung carcinoma patients. Settings and Design: This
      is a Pilot study. Subjects and Methods: It was a Pilot study where biopsies from
      55 fresh previously untreated lung cancer patients visiting the Pulmonary
      Medicine Department of Era's Lucknow Medical College and Hospital Lucknow and
      King George's Medical University were taken for 18 months November 2014-April
      2016, after taking proper informed consent from them. Paraffin blocks were taken
      and stained by hematoxylin and eosin (Sigma) to make the histopathological
      diagnosis and immunohistochemistry was done for detection of CSC marker ALDH1
      (Daco). Statistical Analysis Used: The statistical analysis was done using
      Statistical Package for Social Sciences Version 15.0 Statistical Analysis
      Software. The values were represented in number (%) and mean +/- standard
      deviation. Results: Expression of stem cell marker ALDH1 with the staging of the
      tumor was observed in 62.5% of Stage I, 80% of Stage II, 94.1% of Stage III, and
      100% of Stage IV cases. Statistically, there was a significant association
      between ALDH1expression and stage of disease (P < 0.001). Diagnostic efficacy of
      ALDH1 expression in the detection of any positive clinical stage, it was found to
      be 88.6% sensitive and 90.9% specific. Conclusions: Strong ALDH1 expression
      correlates with higher stage of lung carcinoma making it a prognostic marker
      needing in-depth study.

PMID- 30303137
TI  - Evaluation of CD30/CD4/CD8 in triple-negative invasive ductal carcinoma of breast
      in association with clinicopathological prognostic factors.
AB  - Background: Triple-negative breast cancer (TNBC) lacks the benefits of receptor
      targeted therapeutic strategies. The limitations in treatment options along with
      poor patients' outcome heighten the need for novel approaches. Due to recent
      concentration on the role of biomarkers in prognosis, treatment, and survival of
      various cancer subtypes, this study involves an investigation of CD4, CD8, and
      CD30 markers detected by immunohistochemistry in TNBCs and their association with
      clinicopathological and prognostic factors. Materials and Methods: Tissue samples
      of 85 hormone receptor- and human epidermal growth factor receptor-2-negative
      ductal breast carcinomas extracted from the archive of pathology department.
      Regarding CD4/CD8 ratio, the infiltrated T-lymphocytes were investigated. The
      tumoral tissue regions were also identified to be immunohistochemically assessed
      for the CD30 expression levels. Results: With an elevated CD4/CD8 ratio, a
      significant increase in lymph node involvement was observed (P < 0.05); in
      contrast, increased expression levels of CD8 were related to significant
      reduction of lymph node involvement. CD30 overexpression was found to be
      significantly associated with shortened overall survival (OS) and highly
      involvement of lymph nodes. Conclusion: Following the progression in stage and
      grade of tumor, CD4/CD8 ratio and CD30 expression levels are increased and are
      accompanied by adverse prognosis and poor OS, while CD8-enhanced expression
      carries a favorable prognostic impact as it improves OS status. Therefore, all
      these findings could be of interest in the field of target therapy.

PMID- 30303138
TI  - Prognostic indices predictive of short-term disease-free survival of breast
      carcinoma patients receiving primary surgical treatment in Sri Lanka.
AB  - Background: Breast carcinoma (BCa) is the commonest malignancy among women
      worldwide and in Sri Lanka. Several prognostic indices are described for BCa.
      Aims: To assess clinicopathological features and prognostic indices derived from
      routine clinical, histopathological and immunohistochemical (IHC) data, in a
      cohort of patients undergoing primary surgery for BCa and to determine their
      prognostic impact on short-term disease free survival. Setting and Design: : This
      is a bidirectional cohort study of 208 women undergoing primary surgery for BCa
      at the National Hospital of Sri Lanka, from 2012-2014, excluding post-neoadjuvant
      chemotherapy cases. Material and Methods: Clinical details, tumor size and nodal
      status were obtained from histopathology reports. Histopathology and
      estrogen/progesterone receptor and HER2 status were reviewed. Molecular subtype
      based on IHC was determined. Nodal ratio (number of positive nodes/total number
      retrieved) and Nottingham prognostic index were calculated. Follow up information
      was obtained by patient interviews and record review. Statistical Analysis: Data
      was analyzed by univariate and multivariate Cox regression using SPSS19.0.
      Results: Mean follow-up duration was 27.16 months (0.5-52 months, s = 9.35
      months). 174 (82.9%) remained disease free with 19 (9%) deaths. Thirteen (6.2%)
      survived with metastasis and 4 (1.9%) with recurrences. On univariate Cox
      regression, tumor, nodal and TNM stages, nodal ratio and lymphovascular invasion
      (LVI) were predictive of disease free survival (DFS) (P = 0.001, P = 0.021, P =
      0.022, P = 0.002, P = 0.018). On multivariate analysis TNM stage and LVI were
      predictive of DFS. Conclusion: TNM stage and LVI were the most important
      predictors of short-term disease free survival in this study population,
      confirming that early detection of BCa at a lower stage has a significant impact
      on short-term outcomes.

PMID- 30303139
TI  - Diagnostic utility of CD10 immunohistochemical staining on cellblock in
      differentiating hepatocellular carcinoma from secondary malignancies of liver.
AB  - Background: Differentiation of hepatocellular carcinoma (HCC) from metastatic
      malignancy in liver may be difficult at times on fine-needle aspiration cytology,
      especially in case of moderate-to-poorly differentiated tumors. The benefit of
      cell-block technique is the recognition of histologic pattern of diseases along
      with application of a wide variety of immunohistochemical (IHC) stains to
      differentiate hepatic malignancies. In this study, CD10 IHC staining was done on
      cellblocks prepared from aspirates of clinicoradiologically/cytologically
      suspected malignant liver neoplasms to differentiate HCC from malignancies
      metastasizing to liver. Objective: The objective of the study was to assess the
      diagnostic utility of CD10 IHC stain on cell-block preparation for
      differentiating primary from Secondary malignancies of liver. Materials and
      Methods: Formalin-fixed, paraffin-embedded cellblocks of 61 cases (25 cases of
      HCC and 36 cases of metastatic carcinoma) were prepared from a fine-needle
      aspirate of the suspected malignant liver neoplasm and immunostained using
      monoclonal antibody against CD10. Results: Twenty-two (88%) of 25 cases of HCC
      were positive for CD10 with a canalicular staining pattern. Two (8%) were
      positive for CD10 with membranous and one (4%) with cytoplasmic staining pattern.
      Conclusion: CD10 immunostaining on cellblock is useful in discriminating HCC and
      metastatic carcinoma of the liver with a diagnostic accuracy of 88.52%.

PMID- 30303140
TI  - Intracholecystic papillary-tubular neoplasm of gallbladder: A 5-year
      retrospective pathological study.
AB  - Background: Intracholecystic papillary-tubular neoplasm (ICPN) is a relatively
      new entity which includes neoplastic polyps, adenomas, and papillary neoplasms
      that are >=1.0 cm. This study is done to evaluate the pathological features of
      ICPN and to find out the factors associated with invasion. Materials and Methods:
      This is a 5-year retrospective study in a referral pathology center. A total of
      19 cases of ICPN are found. The cases are analyzed for age and sex distribution,
      clinical suspicion, stages, histological architecture, differentiation, and grade
      of dysplasia. Descriptive statistics and test of significance by Chi-square and t
      test are used in the study. Results: ICPN comprises 23.5% of all gallbladder
      neoplasms. Two-thirds of the cases were suspected radiologically. Age range is 26
      65 years with mean age of 50 years. They are 2.8 times more common in female.
      Approximately one-third of the cases show invasion. The most common histological
      pattern is papillary, followed by papillary-tubular and finally by tubular
      pattern. Pyloric and biliary are the most common differentiation pattern followed
      by oncocytic and intestinal pattern. About three-fourths of the cases are
      associated with high-grade dysplasia mostly diffuse high-grade dysplasia.
      Conclusion: We have found the younger age of presentation, less proportion of
      invasive tumors, fewer tumors with biliary phenotypes, and fewer tumors with high
      grade dysplasia as compared to previous studies. Factors significantly associated
      with invasion are grade and extent of dysplasia particularly diffuse high-grade
      dysplasia.

PMID- 30303141
TI  - Prevalence estimation of microsatellite instability in colorectal cancers using
      tissue microarray based methods - A tertiary care center experience.
AB  - Aim: Microsatellite instability (MSI) pathway is known to be implicated in
      carcinogenesis of 15% colorectal carcinomas (CRC), including 2%-3% of cases of
      Lynch syndrome, as per western literature. MSI status has important prognostic
      and therapeutic implications. The prevalence of MSI in Indian CRC patients is
      unknown. We aimed to determine the prevalence by studying 231 consecutive
      unselected cases of CRC. Methods: Tissue microarrays using duplicate cores per
      case for 141 cases, and whole tissue sections for 90 cases, were used.
      Immunohistochemistry with four mismatch repair (MMR) markers - MLH1, MSH2, MSH6,
      and PMS2 was performed. Molecular analysis for MSI status was performed in 18
      randomly selected cases. Correlation with various clinical and histopathological
      features was done using univariate and multivariate analysis. Results: Loss of
      MMR immunohistochemical (IHC) was seen in 53/231 cases, i.e. 22.94% (95%
      confidence interval 17.52%-28.36%). MLH1-PMS2 dual loss comprised 13.9%, MSH2
      MSH6 7.4%, and isolated PMS2 loss in 1.73% of cases. Univariate analysis showed
      significant association with age (<60 years), right-sided tumor location,
      histologic type, high grade, the presence of severe intratumoral lymphocytic
      (ITL) and peri-tumoral lymphocytic response, and N0 nodal stage. On multivariate
      analysis, independent variables were age < 60 years, right-sided location, and
      severe ITL. Molecular testing for MSI corroborated with the IHC results.
      Conclusion: The study results show a slightly higher prevalence of MSI-H
      phenotype, compared to Western literature, stressing the need for more widespread
      testing for better clinical management and identification of possible hereditary
      colon cancer syndrome.

PMID- 30303142
TI  - Evaluation of topoisomerase II, ki-67, and P53 expression in non-muscle-invasive
      urothelial carcinoma and their clinical significance.
AB  - Background: Transurethral resection of tumor is the main treatment of non-muscle
      invasive urothelial carcinoma, but it is associated with high rate of recurrence
      and/or progression and this arouses the need for adjuvant therapy. Topoisomerase
      II (Top II), KI-67, and P53 are proliferation and cell cycle regulation markers
      that may predict tumor response to therapy. Aim: This study aimed to assess Top
      II, KI-67, and P53 expression and their effect on clinical outcome and response
      to therapy of non-muscle-invasive urothelial carcinoma. Materials and Methods:
      Fifty cases of non-muscle invasive urothelial carcinoma were collected; Top II,
      KI-67, and P53 expression was evaluated. Patients received treatment then tumor
      recurrence was correlated with the expression of previous markers. Results: There
      was a significant association between high Top II score, P53, and KI-67 and high
      tumor grade (P = 0.0001, 0.001, and 0.0001), submucosal infiltration (P = 0.0001
      and 0.01), and recurrence (P = 0.01, 0.001, and 0.001). Conclusion: Top II, P53,
      and KI-67 may predict tumor response to therapy and the clinical outcome in non
      muscle-invasive urothelial carcinoma.

PMID- 30303143
TI  - BRAFV600E mutation in hairy cell leukemia: A single-center experience.
AB  - Background: BRAFV600E mutation has been reported as a unique genetic lesion of
      hairy cell leukemia (HCL), a subset of which lacks this lesion and shows adverse
      outcomes. Aims: To determine the prevalence of BRAFV600E in HCL from our center
      and derive clinicopathological correlation, if any. Materials and Methods: A 9
      year retrospective analysis of 46 consecutive cases of HCL diagnosed on
      morphology and immunophenotyping was done. Stained smears were used as samples
      for amplification refractory mutation system polymerase-chain reaction using
      fluorescent primers for mutation detection. Results: BRAFV600E mutation was
      detected in 41/46 patients (89.1%) while absent in control samples of chronic
      lymphocytic leukemia. Cases mimicking HCL-variant clinically or
      immunophenotypically too showed the presence of this mutation. HCL with mutated
      BRAF presented at a younger age. No statistical difference in blood counts, tumor
      load, and immunophenotype patterns existed among BRAF mutated and unmutated
      group. Nine patients (45%) with mutated BRAF had residual disease following
      treatment with cladribine. Conclusion: BRAFV600E mutation analysis has a
      definitive role in the diagnosis of HCL.

PMID- 30303144
TI  - Student perception of peer teaching and learning in pathology: A qualitative
      analysis of modified seminars, fishbowls, and interactive classroom activities.
AB  - Context: Peer-assisted teaching and learning (PTL) is being experimented in
      different medical universities worldwide. It is a learner-centered approach
      involving students through active learning strategies. Aims: To study the student
      perception of PTL in methods such as group-led seminars and fishbowls, in
      classroom through various interactive activities; compare and find out the
      student acceptability and efficacy of each of these methods in learning
      conceptual topics such as various types of anemia. Subjects and Methods: Medical
      students of second-year professional course were subjected to PTL in classroom
      during allotted teaching hours for 10 successive sessions using group-led
      modified seminars, fishbowls, and different formality-level interactive
      activities such as street plays, prop sessions, quiz sessions, to make them
      understand the clinical features and presentation of different types of anemia
      through understanding of etio-pathogenesis. To ascertain the aspects that
      influenced learning, focus group discussions were conducted in small groups
      consisting of 14 students and one facilitator in each group. Qualitative thematic
      analysis was performed on transcripts of the audio recordings by authors.
      Results: The emerging themes from qualitative analysis of transcripts were
      pertaining to teacher, student, and organization. We found motivation, interest,
      and involvement of peer teacher, student behavior and collaboration, contact time
      between students and facilitator, preparation time, coherence with other
      curricular activities, group size and composition, suitability of topic for the
      kind of activity, and availability of material for preparation as few sub-aspects
      affecting learning. Conclusion: For PTL to be effective, adequate transfer of
      knowledge through good peer teacher involvement, learner receptiveness, and
      adequate contact time is needed. Proper preparation with suitability of topics
      for the type of activity, alignment of seminars with other activities, and course
      coherence are prerequisites for the same.

PMID- 30303145
TI  - Infective endocarditis due to Streptococci and Enterococci: A 3-year
      retrospective study.
AB  - Introduction: Infective endocarditis (IE) is an infection of the heart valves
      with an aggregation of bacteria in a fibrin plaque called vegetation. Aims and
      Objectives: This is a retrospective study of all infective endocarditis cases due
      to alpha haemolytic streptococci and enterococci. Methods: All cases of infective
      endocarditis cases due to alpha haemolytic streptococci and enterococci in a
      period of three years from 1st January 2010 to 31st December 2012 were included.
      Isolation of the same organism from more than one set of blood cultures was taken
      as a confirmed case of infective endocarditis. Clinical and serological
      parameters were recorded using a proforma. Results: Native valve endocarditis was
      more common with only five prosthetic valves being involved. Out of 89 clinically
      suspected cases of IE in the three years from Jan 2010 to Dec 2012, for which
      blood was sent for culture, 63(70.78%) samples were positive by culture. Of
      these, 42/63(66.66%) were due to alpha-lytic Streptococci, enterococci and rare
      gram positive cocci. The rare ones included Enterococcus gallinarum, abiotropha
      defective, Vagococcus fluvialis and Nutritionally Variant Streptococci(NVS). High
      level Aminoglycoside resistance(HLAR) was also encountered. The varied and
      important features of these isolates are discussed. Complications and treatment
      are described. Conclusion: From a clinical microbiology point of view, the major
      challenge faced by the microbiologist in diagnosis of IE is proper aseptic
      collection of sample before starting antibiotics with a need for multiple samples
      to detect and also to prove the causative organism. Sensitivity reporting can be
      a difficult task in the context of NVS, HLAR and gram positives that are slow
      growing. Congestive failure and embolisation occurs even when the antibiotic
      treatment is successful.When patients go in for complications, it is very rarely
      due to wrong antibiotics.

PMID- 30303146
TI  - The clinicopathologic and immunohistochemical features of villoglandular
      adenocarcinoma of uterine cervix.
AB  - Aim: Villoglandular adenocarcinoma (VGA) of the uterine cervix is a variant of
      endocervical adenocarcinoma. However, the clinicopathologic and
      immunohistochemical features of VGA are still unclear. The aim of this study was
      to investigate the clinicopathologic and immunohistochemical features of VGA.
      Materials and Methods: A total of 20 VGA patients were identified among 852
      patients diagnosed with cervical cancer and enrolled in this study. The
      immunohistochemical levels of Ki-67, P53, P16, progesterone receptor (PR),
      carcinoembryonic antigen (CEA), vimentin (Vim), and estrogen receptor (ER) were
      measured by immunohistochemistry. Results: VGA was prevalent in younger women and
      presented favorable prognosis. Ki-67, P16, and CEA were highly expressed in VGA
      tissues, while PR expression was hardly to be detected. The positive rates of Ki
      67, CEA, and P16 were 90.0%, 90.0%, and 85.0%, respectively, which were
      significantly higher compared with PR (5.0%, P < 0.001). In addition, the
      positive rates of P53, Vim, and ER in VGA tissues were 55.0%, 50.0%, and 40.0%,
      respectively. However, the expression levels of Ki-67, P53, P16, PR, CEA, Vim,
      and ER were not significantly associated with clinical features (P > 0.05).
      Conclusion: These data indicate that VGA is a rare cervical adenocarcinoma, which
      is prevalent in younger women, and presents favorable prognosis. Detection of Ki
      67, P53, P16, PR, CEA, Vim, and ER would be beneficial for the diagnosis of VGA.

PMID- 30303147
TI  - Adult T-cell leukemia/lymphoma and acquired immunodeficiency syndrome - CD4+ T
      cell malignancy in CD4+ T-cell deficient status: A paradox.
AB  - CD4 counts along with viral loads are important parameters in the monitoring of
      human immunodeficiency virus (HIV) infection. Human T-cell lymphotropic virus
      type I (HTLV-I) is known to be an etiological agent for adult T-cell
      leukemia/lymphoma (ATLL). Coinfection of HTLV-I and HIV is well known in regions
      with high seroprevalence, and there is no published data in the Indian scenario.
      We present an interesting case of occurrence of CD4+ T-cell proliferation in a
      known beta thalassemia major with acquired HIV seropositivity accompanied by
      simultaneously increasing CD4+ counts and viral loads. Further workup revealed
      ATLL with an underlying HTLV infection.

PMID- 30303148
TI  - Chronic granulomatous disease presenting with small bone osteomyelitis in a young
      child: A case report.
AB  - Chronic granulomatous disease (CGD) is a life threatening inherited disorder with
      varied clinical presentations often characterized by recurrent bacterial and
      fungal infections along with widespread granulomatous tissue response. The
      disease results from phagocytic defects characterized by deficiencies in
      oxidative burst of neutrophils. Nitroblue tetrazolium reduction test (NBT) and
      Dihydrorhodamine (DHR) with PMA stimulation by flow cytometry are quick, simple,
      sensitive and specific laboratory tests that help establish early and reliable
      diagnosis of CGD with an overall improvement in survival and disease prognosis.
      We report a case of 2-year old child who presented with small bone osteomyelitis
      involving bilateral feet and was later diagnosed to have autosomal recessive CGD
      due to mutation in NCF1 gene.

PMID- 30303149
TI  - Immunohistochemical differentiation between spindle cell lipoma and neurofibroma
      of oral cavity using CD34 and SOX10.
AB  - Spindle cell lipoma (SCL), also called as pleomorphic adenoma, is a rare variant
      of lipoma histopathologically characterized by an admixture of mature fat cells
      with spindle cells and occasionally mast cells with myxoid connective tissue
      stroma and thick bends of birefringent collagen. Although buccal mucosa is the
      most common location for oral lipomas, for SCL, it is an exceedingly rare
      location. We report a case of an asymptomatic swelling of buccal mucosa that
      simulated the features of neurofibroma on histopathological examination, and the
      final diagnosis of SCL was made on the basis of immunohistochemical features.
      This is the first documentation of oral SCL using SOX10 to achieve the final
      diagnosis.

PMID- 30303150
TI  - Dedifferentiation of oncocytic epithelial-myoepithelial carcinoma to
      mucoepidermoid carcinoma in parotid gland: A rare case report.
AB  - Epithelial-myoepithelial carcinomas (EMCs) account for <1% of all salivary gland
      malignancies. Till now, 23 cases of dedifferentiated EMC have been reported to
      the best of our knowledge. However, dedifferentiation of oncocytic EMC to
      mucoepidermoid carcinoma is extremely rare. A 38-year-old female presented with
      right post aural swelling 4 cm * 2 cm in size for 6 months. Surgical excision was
      carried out, and we received partly skin-covered tissue 5 cm * 2 cm in size.
      Sections examined showed features of oncocytic EMC dedifferentiating into
      mucoepidermoid carcinoma. Myoepithelial component showed oncocytic change which
      was highlighted by p63.

PMID- 30303151
TI  - Cutaneous melanoma in childhood presenting as intraparotid lymph node metastasis.
AB  - Cutaneous melanoma in childhood is a rare disease. Rendering a clinical diagnosis
      of melanoma in pediatric patients is confounded by the fact that pigmented
      lesions in pediatric patients do not conform to the ABCDE rules applicable to
      adult patients. Furthermore, making a histologic diagnosis of cutaneous melanoma
      in childhood is also difficult with no universally accepted criteria applicable
      to pediatric melanomas. We report the case of a 5-year-old child presenting with
      intraparotid lymph node metastasis who was later found to have melanoma involving
      periorbital region. It is proposed that careful analysis of histologic features
      as well as the additional information provided by immunohistochemistry should
      allow for a correct diagnosis in most cases of melanoma in children.

PMID- 30303152
TI  - Bilateral submandibular swelling diagnosed as tuberculous lymphadenitis in an
      asymptomatic patient: A rare case report.
AB  - In India, tuberculosis (TB) is a prevalent systemic disease and number of people
      who die with TB is increasing year by year. TB can be life-threatening, and there
      is a high mortality rate of systemic infection with TB. Although extrapulmonary
      TB (EPTB) is a rare form of TB, its prevalence is increasing day-by-day. Reported
      here is a case of a 28-year-old female patient with a painless swelling
      bilaterally in the submandibular region. She was diagnosed with bilateral
      submandibular tuberculous lymphadenitis. Tuberculous lymphadenitis, when
      occurring in the cervical region, continues to be a common cause of EPTB.
      Thorough knowledge of this condition is important as it can help in early
      diagnosis leading to prompt treatment of the patient and prevent further
      complications.

PMID- 30303153
TI  - Pericardial mesothelioma presenting as chronic constrictive pericarditis. A
      series of three cases from a single institution.
AB  - Pericardial mesotheliomas are rare tumors which often present with features of
      constrictive pericarditis. We present clinical, imaging, histological, and
      immunohistochemical findings of three cases presenting with chronic constrictive
      pericarditis. Two of these cases were initially treated as tuberculous
      pericarditis. Histologically, all the three cases were of an epithelioid type and
      showed positivity for more than one mesothelial markers. Two patients had a fatal
      outcome, and one was lost to follow-up.

PMID- 30303154
TI  - Well-differentiated liposarcoma of the breast arising in a background of
      malignant phyllodes tumor in a pregnant woman: A rare case report and review of
      literature.
AB  - Pure mesenchymal sarcomas and phyllodes tumor with sarcomatous differentiation of
      the breast are rare tumors. Primary breast sarcomas are a heterogenous group of
      neoplasms which include malignant fibrous histiocytoma, fibrosarcoma,
      angiosarcoma, leiomyosarcoma, osteosarcoma, rhabdomyosarcoma, and liposarcoma.
      Sarcomatous differentiation in phyllodes tumor is seen in the form of
      angiosarcoma, chondrosarcoma, leiomyosarcoma, osteosarcoma, rhabdomyosarcoma, and
      liposarcoma. Here, we report a case of a 28-year-old pregnant woman with a breast
      lump during her second trimester which drastically increased in size in the
      postpartum period. Wide local excision revealed a malignant phyllodes tumor with
      liposarcomatous differentiation. Later, the patient underwent completion
      mastectomy which showed residual tumor.

PMID- 30303155
TI  - Duodenal gangliocytic paraganglioma: A rare cause for gastrointestinal polyp.
AB  - Duodenal gangliocytic paragangliomas are rare neoplasms often arising in the
      duodenum in close proximity to the ampulla of Vater. These neoplasms are
      considered to have a benign behavior with lymph node metastases being a rare
      phenomenon and distant metastases even more so. Although a standardized treatment
      has not been determined, a margin-free tumor resection seems to be the best
      treatment modality. We report herein the case of a 36-year-old female who
      presented with abdominal pain and was found to have a polyp in the second part of
      duodenum which was excised endoscopically. Histopathology and
      immunohistochemistry revealed characteristic features of this rare tumor.

PMID- 30303156
TI  - Gastric carcinoma and acute myeloid leukemia: A case report of a double
      malignancy.
AB  - A double malignancy involving a solid organ and hematopoieteic system is rare. We
      report an interesting case of gastric adenocarcinoma with subsequent development
      of acute myeloid leukemia, in the absence of any therapeutic intervention.

PMID- 30303157
TI  - An unusual case of hepatic lymphoma with multiple epithelial malignancies.
AB  - Primary hepatic mucosa-associated lymphoid tissue lymphoma (MALToma) is a rare
      entity. Its coexistence with other malignancies is even rarer. Only few case
      reports of its association with other malignancies mostly gastric and colon
      cancer have been published. We report a case of primary MALToma of liver in an
      unusual setting of dual solid malignancy.

PMID- 30303158
TI  - Adrenal medullary hyperplasia with coexistent cerebral angiomas.
AB  - Sporadic adrenal medullary hyperplasia (AMH) is a rare entity and mimics
      pheochromocytoma clinically as well as pharmacologically. It is characterized by
      increase in adrenal medullary cells with the expansion of cells into areas
      normally not seen. A 59-year-old male presented with chronic hypertension and
      raised 24-h urinary normetanephrine levels. Radiological and clinical possibility
      of pheochromocytoma led to left transperitoneal laparoscopic adrenalectomy.
      Histopathology, however, showed increase in adrenal medullary to cortical ratio,
      further confirmed by immunohistochemistry. The absence of any well-defined lesion
      led to the diagnosis of AMH. Furthermore, on routine imaging, two asymptomatic
      cavernous hemangiomas were seen. We present this case to reiterate that AMH is an
      entity which should be considered as a differential for pheochromocytoma.
      Furthermore, the presence of asymptomatic cavernous hemangiomas in the cerebrum,
      in this case, makes it rarer since this sporadic association is seldom seen.

PMID- 30303159
TI  - Primary intrauterine dysgerminoma in a pregnant woman: A rare case report.
AB  - Primary extraovarian dysgerminoma is very rare. Nearly all reported uterine germ
      cell tumors are nondysgerminoma. Herein, we reported a primary intrauterine
      dysgerminoma. A 21-year-old pregnant woman G2 L1 with a gestational age of 33
      weeks referred to an obstetric ward with a chief complaint of labor pain and
      membrane rupture. Ultrasonography showed a large hypoechoic lobulated area
      adjacent to the lower part of her uterus. She underwent an operation and a huge
      mass was detected in her uterus, which was extended to her pelvic floor.
      Histopathological and immunohistochemical examinations were consistent with
      dysgerminoma.

PMID- 30303160
TI  - Polyp of the uterine cervix with heterologous fatty tissue.
AB  - This report documents an uncommon case of choristomatous cervical polyp
      containing fat tissue. The patient was a 24-year-old female who presented with
      irregular intermenstrual bleeding. On examination, a polypoid lesion with smooth
      outlines, measuring 1 cm in diameter was removed. Microscopic examination
      demonstrated abnormal fibrous stroma, devoid of endocervical glands, containing
      mature adipose tissue, and thick-walled blood vessels. The lesion was covered by
      a typical mature squamous cell outer lining. To the best of our knowledge, this
      is only the second report of an adipose tissue arising from the cervical wall.
      Further clinicopathologic considerations are needed to elucidate the origin of
      the fatty component in cervical polyps.

PMID- 30303161
TI  - Malignant Sertoli cell tumor of the testis masquerading as seminoma with bone
      metastasis.
AB  - Sex cord-stromal tumors of the testes are rare malignancies as compared to germ
      cell tumors. Pure Sertoli cell tumors are still rare representing <1% of
      testicular cancers and the malignant forms are too rare. Furthermore, the
      occurrence of metastasis in such cases is extremely rare with <30 cases reported
      in literature so far to the best of our knowledge. We present herein a case of
      malignant Sertoli cell tumor in a 48-year-old male who was initially misdiagnosed
      as seminoma based on histology and clinical presentation. Four months later, he
      presented with symptoms due to bony metastasis and found to have widespread
      metastatic disease which is a very rare presentation of Sertoli cell tumors.
      Diagnosis of sex cord-stromal tumor requires high index of suspicion as these
      tumors are most of the times misdiagnosed as germ cell tumors due to their rare
      incidence and atypical presentation leading to mismanagement. Timely diagnosis at
      an early stage can provide therapeutic benefit due to lack of well-defined
      treatment options at advanced stages.

PMID- 30303162
TI  - Orchitis: An unusual presentation of polyarteritis nodosa.
AB  - Polyarteritis nodosa (PAN), a systemic necrotizing vasculitis with multiorgan
      development, is generally restricted to the medium-sized muscular arteries. The
      varied initial clinical presentations of PAN can lead to a delayed diagnosis. We
      present the case of a middle-aged male patient who presented with an acute onset
      right-sided testicular pain as the initial clinical symptom with ischemic changes
      on ultrasonogram, thereby requiring orchiectomy. This was reported to be a case
      of tubercular epididymo-orchitis. On review, the biopsy revealed features of
      necrotizing arteritis as seen in PAN with fibrinoid necrosis and giant cells,
      thus highlighting the fact that vasculitis due to PAN may have a localized
      presentation at the time of diagnosis. PAN should be distinguished from other
      causes of epididymo-orchitis and other vasculitis lesions, the most common being
      tubercular etiology in the Asian population.

PMID- 30303163
TI  - Synovial hemangiomas of wrist and ankle joint: A report of two rare cases.
AB  - Synovial hemangioma is a rare, benign, vascular tumor of synovium leading to
      joint pain and swelling. The most common site is the knee joint, but rare cases
      involving other sites have also been reported. We report two rare cases of
      synovial hemangioma, one involving the ankle joint and other involving the wrist
      joint. Histopathology is the gold standard for diagnosis of these cases. Early
      treatment is warranted to prevent the risk of permanent joint damage.

PMID- 30303164
TI  - Keratomycosis due to Purpureocillium lilacinum: A case report from Sub-Himalayan
      region of Uttarakhand.
AB  - The fungus Purpureocillium lilacinum previously known as Paceliomyces lilacinus
      is an emerging pathogen that can cause severe human infections including
      devastating oculomycosis. Treatment with traditional antifungals often fails, and
      the organism shows variable susceptibility to novel triazoles. We hereby report a
      case of keratomycosis caused by Pur. lilacinum in an immunocompetent male patient
      following trauma. The patient was successfully treated with voriconazole. The
      drug shows good activity against Pur. lilacinum and could be a promising
      therapeutic alternative to treat infections caused by this fungus, which
      generally shows resistance to conventional antifungal agents including novel
      triazoles.

PMID- 30303165
TI  - Fibrillary glomerulonephritis in a human immunodeficiency virus-positive,
      hepatitis C-negative Indian patient: Expanding the profile of renal involvement
      in human immunodeficiency virus infection.
AB  - Highly active anti retroviral therapy (HAART) has dramatically improved life
      expectancy of human immunodeficiency virus (HIV) infected patients, converting
      HIV infection into a chronic illness with associated changes in its attendant
      renal complications. The past two decades have witnessed a decrease in the
      prevalence of HIV associated nephropathy (HIVAN), traditionally considered to be
      the hall mark of renal involvement in HIV infection. Simultaneously a host of
      other glomerular and tubulo-interstitial diseases have emerged, expanding the
      spectrum of HIV associated renal diseases, predominant among which is HIV
      associated immune complex mediated kidney diseases (HIVICK). Of the diverse
      glomerular diseases constituting HIVICK, fibrillary glomerulonephritis (FGN)
      remains a rarity, with only two existing reports to date, confined to patients co
      infected with Hepatitis C virus (HCV). The pathogenetic role of HIV in these
      patients remains under a cloud because of previously well established association
      of HCV infection and FGN. We report a case of FGN in a HIV seropositive, HCV
      negative Indian patient, highlighting the diagnostic electron microscopy (EM)
      findings of FGN and strengthening the causal association of HIV with FGN. In view
      of increasing heterogeneity of renal complications in HIV infection, the
      diagnostic utility of a comprehensive renal biopsy evaluation inclusive of EM is
      emphasized for appropriate selection of treatment modalities.

PMID- 30303166
TI  - Extensive trophoblastic differentiation in case of an endometrial carcinoma.
AB  - Trophoblastic differentiation of endometrial carcinoma is extremely rare, till
      date 18 cases reports are there in the literature. A 68-year-old postmenopausal
      female presented with abnormal vaginal bleeding. Histopathologically, there were
      areas of serous carcinoma with trophoblastic differentiation (~90%). On
      immunohistochemistry, the trophoblastic component was positive for beta-human
      chorionic gonadotropin (hCG), HPL and EMA. IHC confirmed the diagnosis of serous
      carcinoma with trophoblastic differentiation. The clinicopathological features of
      18 previously reported cases of trophoblastic differentiation in the uterine
      tumor were analyzed in addition to the present case.

PMID- 30303167
TI  - Bilateral renal fungal balls in an infant.

PMID- 30303168
TI  - MiT family translocation-associated (TFE3 positive) renal cell carcinoma of
      childhood.

PMID- 30303169
TI  - Bone marrow edema mimicking amyloid.

PMID- 30303170
TI  - Partial "fetus-in-fetu".

PMID- 30303171
TI  - Abnormal morphological appearance of Klebsiella pneumoniae in blood culture: A
      microscopic observation.

PMID- 30303172
TI  - Lipofibroadenoma with B1 thymoma: A case report of a rare thymic tumor.

PMID- 30303173
TI  - Canalicular adenoma arising from the nasal septum in a child: First case report.

PMID- 30303174
TI  - Primary pulmonary pleomorphic adenoma: A rare case report.

PMID- 30303175
TI  - Primary pulmonary melanoma: An unexpected diagnosis.

PMID- 30303176
TI  - Tumefactive demyelination versus tumor; A diagnostic dilemma: Role of electron
      microscopy.

PMID- 30303177
TI  - Isolated spinal epidural hydatid disease: A diagnostic challenge in a needle core
      biopsy.

PMID- 30303178
TI  - Erratum: Primary follicular lymphoma of disguised as multiple miliary like
      lesions: A case report and review of literature.
AB  - [This corrects the article DOI: 10.4103/IJPM.IJPM_126_17].

PMID- 30303179
TI  - Laparoscopic Surgery Within an Enhanced Recovery after Surgery (ERAS) Protocol
      Reduced Postoperative Ileus by Increasing Postoperative Treg Levels in Patients
      with Right-Side Colon Carcinoma.
AB  - BACKGROUND The aim of this study was to determine the effects of laparoscopic
      surgery within an ERAS program on outcomes and immunological function in patients
      with a carcinoma in the right colon. MATERIAL AND METHODS Patient data were
      acquired from a prospectively maintained database, and 176 patients diagnosed
      with right colon carcinoma with surgery were selected from the database. These
      patients were divided into a laparoscopic group (Lap group, n=86) and an open
      operation group (Open group, n=90). All patients received treatment according to
      a standardized ERAS protocol. We collected data on CRP levels, CD4+/CD8+ ratios,
      and Treg values in peripheral blood, baseline and surgical characteristics,
      postoperative complications, and postoperative ileus (POI). RESULTS Circulating
      CD4+/CD8+ ratios and Treg values were decreased and CRP levels were increased in
      both groups after the operation. However, the values in the Lap group patients
      recovered much more quickly than those of patients in the Open group (P<0.05).
      Patients undergoing laparoscopic surgery had significantly less preoperative
      bleeding (P<0.01), reduced ratio of overall POI (mainly early ileus), and shorter
      postoperative hospital stay (P=0.03). Multivariate logistic regression analysis
      showed that POD1 Treg value was an independent predicator for postoperative ileus
      in patients with right colon carcinoma resection. CONCLUSIONS In patients with a
      carcinoma in the right colon, laparoscopic surgery within an ERAS protocol leads
      to better immunity preservation after surgery, and POD1 Treg value may be an
      independent predicator for postoperative ileus, which could, at least in part,
      explain the shorter hospital stay after surgery.

PMID- 30303182
TI  - [We must not neglect new realities: the drama of migrants.]
AB  - Since 2014 1.8 million migrant people arrived in Europe from Italy, Spain and
      Greece. It represents a quarter of the London population. And other 16 thousand
      are the deaths in the Mediterranean Sea in four years. Yet, there are those who
      still talk about invasion, making it a weapon for political propaganda, and the
      health sector is among the most exploited. The Italian politicians themselves are
      at the forefront on the diffusion of fake news on the health conditions of people
      arriving in Europe, riding the long wave of fear of the unknown foreign people,
      and of the possibility of a contagion. However, data tell a completely different
      story: migrants who arrive in Europe does not bring vulnerability to the natives:
      they are vulnerable, and they need first of all our protection. There is no
      evidence of outbreaks of infectious diseases, and in any case border controls are
      carried out, and they can identify anyone who is not in good health before
      landing. The same can not be said of mental illness. Rape, torture, murders: this
      is what people arrived in Italy from Libya have lived. This should be the
      starting point - not the refusal to give hospitality - for aligning our
      communities with the UN warning from here until 2030: no one left behind.

PMID- 30303183
TI  - [Systems medicine and complexity: rethinking health management and hospital
      modelling.]
AB  - We have reached the awareness that diseases, far from being simple altered health
      states, are characterized by intrinsic emerging and adaptive properties,
      requiring an interdisciplinary, global and systemic approach, oriented towards
      integration and coordination, rather than an atomic and disintegrated logic. A
      new approach is needed, "systems medicine", defined as an interdisciplinary field
      of study that looks at the systems of the human body as part of an integrated
      whole, incorporating biochemical, physiological, and environment interactions.
      This new kind of medicine addresses diseases and their interrelationships in a
      scale invariant, holistic and systematic "multi-axial" way, analysing apparati,
      organs, tissues, cells, molecules, always taking care of the relationships with
      the relative ecosystem. Given this dramatic change in the process of learning,
      investigating and approaching diseases, the hospital itself has to evolve
      continuously, changing strategies and structures. Hospital management has to be
      re-designed and re-configured in order to face and govern complex systems. Health
      management today must be flexible, able to absorb and incorporate complexity, and
      learn from it, reinforcing itself. Complexity must not be avoided. It is, indeed,
      an opportunity to be considered in the strategic planning and programming
      processes. Intuition, creativity and flexibility are the abilities and
      competences of a manager in a complex environment.

PMID- 30303184
TI  - [ROBIS: a new tool to assess risk of bias in systematic reviews was developed.]
AB  - OBJECTIVE: To develop ROBIS, a new tool for assessing the risk of bias in
      systematic reviews (rather than in primary studies). STUDY DESIGN AND SETTING: We
      used four-stage approach to develop ROBIS: define the scope, review the evidence
      base, hold a face-to-face meeting, and refine the tool through piloting. RESULTS:
      ROBIS is currently aimed at four broad categories of reviews mainly within health
      care settings: interventions, diagnosis, prognosis, and etiology. The target
      audience of ROBIS is primarily guideline developers, authors of overviews of
      systematic reviews ("reviews of reviews"), and review authors who might want to
      assess or avoid risk of bias in their reviews. The tool is completed in three
      phases: 1) assess relevance (optional), 2) identify concerns with the review
      process, and 3) judge risk of bias. Phase 2 covers four domains through which
      bias may be introduced into a systematic review: 1) study eligibility criteria;
      2) identification and selection of studies; 3) data collection and study
      appraisal; and 4) synthesis and findings. Phase 3 assesses the overall risk of
      bias in the interpretation of review findings and whether this considered
      limitations identified in any of the phase 2 domains. Signaling questions are
      included to help judge concerns with the review process (phase 2) and the overall
      risk of bias in the review (phase 3); these questions flag aspects of review
      design related to the potential for bias and aim to help assessors judge risk of
      bias in the review process, results, and conclusions. CONCLUSIONS: ROBIS is the
      first rigorously developed tool designed specifically to assess the risk of bias
      in systematic reviews.

PMID- 30303185
TI  - ?

PMID- 30303186
TI  - ?

PMID- 30303187
TI  - [Depression in pregnancy: focus on the safety of antidepressant drugs.]
AB  - Antepartum depression, frequently in comorbidity with anxiety disorders, is a
      severe psychopathological condition frequently reported in pregnancy and in many
      cases associated with obstetric and neonatal complications and potential negative
      consequences on child neurodevelopment. However, the pharmacological treatment of
      depression, during pregnancy generates a lot of concerns about the risks of such
      treatment for the fetus development and the neonatal health. The aim of this
      review is to present a selection of the latest international literature including
      recent original studies, systematic reviews, meta-analyses and recommendations
      from the guidelines, both on the risks of an untreated depressive disorders and
      on the risk of antidepressant therapy during gestation with drugs belonging to
      the SSRI and SNRI (SRI) class. An updated information of the recent risk-benefit
      data of these drug treatments in women with affective disorders in pregnancy may
      actually enable better and more conscious management of these disorders, not only
      for those working in the mental health field but also for general practitioners
      and those of other medical specialties.

PMID- 30303188
TI  - [Dementia in the real world.]
AB  - More than with other diseases, the diagnosis of dementia must be made carefully,
      as it can have a huge impact on both the patient's social and legal status and
      the caregiver's own health. Special attention should be put in avoiding
      diagnostic errors at the time of symptom onset, because a diagnosis made
      explicitly can affect the patient's self-esteem. If the diagnosis is uncertain,
      we would recommend not performing unnecessary investigation but rather waiting to
      get a clearer clinical picture. Dementia, unfortunately, is reversible or
      partially reversible by drug therapy only in very few cases. We here describe
      common diagnostic challenges and doubts, and how to manage patients with known
      dementia in relation to changes in the environment and social interactions.
      Dementia strongly affects a person's well-being, including maintaining a social
      life and interpersonal relationships, with either the caregiver and the family.

PMID- 30303189
TI  - ?

PMID- 30303191
TI  - [Remembering Mariuccia Ottone].

PMID- 30303190
TI  - [Summer 2018: a nursing centered listening].

PMID- 30303192
TI  - [Patients classification according the intensity of care in an Emergency
      Department].
AB  - : . Patients classification according the intensity of care in an Emergency
      Department. INTRODUCTION: The increasing number of Emergency Department (ED)
      admittances coupled with the limited availability of hospital beds requires a
      patients classification according their intensity of care. Among the available
      classification systems the Tri-Co (Corridor triage) system, could fit ED patients
      and was therefore progressively adapted and tested to be used in the ED. AIM: To
      assess the correct allocation of patients according to the intensity of care.
      METHODS: Eight versions of the Tri-Co were progressively modified and tested. The
      Final Modified Tri-Co system was used in 111 randomly selected index days, in
      different time slots, on all adult patients admitted to ED from May to November
      2017 and allocated according to the traditional system (1008 observations).
      RESULTS: The vast majority of patients (88%) was placed in a section adequate to
      their intensity of care; 8% in a sector with higher and 4% with lower intensity
      of care compared to their needs. The comparison between the allocation based on
      clinical assessment and Tri-Co scores highlighted the reliability of the Tri-Co.
      The alpha Crombach of the modified IDA scale was 0.724. CONCLUSIONS: The Modified
      Tri-Co system allows the early classification of patients and their assignment to
      the adequate level of care.

PMID- 30303193
TI  - [Extent and type of implicit rationing of nursing care in seven South Tyrolean
      hospitals: a descriptive study].
AB  - : . Extent and type of implicit rationing of nursing care in seven South Tyrolean
      hospitals: a descriptive study. INTRODUCTION: Implicit rationing of nursing care
      is an international phenomenon, defined as withholding of or failure to carry out
      necessary nursing interventions due to a lack of nursing resources. AIMS: To
      describe the extent and type of nursing care implicitly rationed in South
      Tyrolean hospitals, and to explore differences across clinical areas and between
      registered nurses (RNs) and support staff. METHODS: The Basel Extent of Rationing
      of Nursing Care (BERNCA) questionnaire was completed between September and
      November 2015, by 934 RNs and support staff of the seven hospitals, involved in
      direct adult patient care (24 medical, 13 surgical, 5 rehabilitation, 4 intensive
      care units). Descriptive and explorative analyses were performed. RESULTS: The
      most rationed activities concerned "nursing care planning" (37.3%), "surveillance
      of confused patient" (30.7%), "providing emotional support" (30.1%) and "talking
      with patients and family" (28.4%). Of the ten most rationed activities, seven
      were common to RN and support staff, and across clinical areas, although with
      different frequencies. Significant differences between clinical areas were
      observed for: "nursing care planning", "rehabilitation care", and
      "comfort/talking with patients and family". DISCUSSION: Implicit rationing of
      nursing care occurs in South Tyrolean hospitals, mainly related to care planning
      and documentation. Higher priority is given to activities related to direct
      patient care. Further investigations on priority setting to increase the
      awareness among frontline nurses of what is rationed, and to guarantee the safety
      and quality of care is warranted.

PMID- 30303194
TI  - [The missed care in Nursing Homes: a pilot study].
AB  - : . The missed care in Nursing Homes: a pilot study. INTRODUCTION: To date missed
      care have been described mostly in hospitals and data on nursing homes (NH) are
      missing. AIM: To describe missed care in NH residents identifying their perceived
      impact and seriousness. METHODS: A pilot study was conducted in 10 Piedmont NHs.
      For each omitted or delayed care on 20 residents observed for 3 consecutive days,
      the nurses provided information on the type of care, and information on the
      residents and on the organization were collected. RESULTS: Twenty-three nurses
      reported 57 missed care for 44/200 residents (22%; median 5 for each NH, range 0
      13). Twenty-five missed/omitted care on 20 residents were considered of
      medium/high severity: 14 (56%) involved drug therapies and 5 (20%) the monitoring
      of vital signs. The level of severity derived from the distress caused to the
      resident, the risk of deterioration of residents'conditions and the repeated
      omissions on the same resident. Of the 32 missed care on 25 residents, judged of
      limited impact, the more frequent were dressing changes (12, 37.5%), and drugs
      administration (10, 31.3%). The most frequent reasons for delay/omission were
      unplanned events (16, 28.1%), shortage of nurses (12, 21.1%), and residents'
      clinical conditions (9, 15.7%). CONCLUSIONS: Missed care occur also in NHs. If
      staff shortage play a key role among potentially modifiable factors, a sizeable
      number of omission is associated to unlikely forseeable or avoidable events.

PMID- 30303195
TI  - [The measurement of missed care: problems and pitfalls].

PMID- 30303197
TI  - [Health care as cultural-political indicator of the society: the role of general
      and specialized publishers].

PMID- 30303196
TI  - [The nurses of the Ospedale Maggiore of Milan during the First World War. Peace,
      rights and dignity of work].
AB  - : . The nurses of the Ospedale Maggiore of Milan during the First World War.
      Peace, rights and dignity of work. INTRODUCTION: During the First World War the
      Hospitals of the big cities had to care for the people injured in the war places.
      To face this challenge, important changes in the internal organization had to be
      implemented. OBJECTIVE: To investigate how the First World War changed the
      working conditions of the nurses on duty at the Ospedale Maggiore and to
      contribute to outline the professional identity during the years of the conflict.
      METHODS: The correspondence between the female nursing staff and the hospital
      administration in the time span between from 1915 to 1918 was examined. The
      documents were retrieved in the historical archive of the Ospedale Maggiore from
      November 2017 to march 2018 and were analyzed through the methodology of historic
      research according to Chabod. RESULTS: During the First World War the nurses
      asked the hospital administration for changes of their working conditions, which
      had become unbearable because of the conflict. They obtained improvements
      concerning: a reduction in nightshift work hours, the employment of 86 nurses to
      guarantee a day off every ten days, replacement of staff in case of absence,
      increase in salary, paid sick leave. CONCLUSIONS: The nurses of the Ospedale
      Maggiore of Milan during the First World War, hoping for peace, stood out for
      their diligence in the care of the sick both civilians and militaries. Besides,
      they managed to obtain the recognition of they rights and dignity in the
      workplace.

PMID- 30303198
TI  - [Missed nursing care and italian nursing practice: preliminary finding of a
      consensus conference].
AB  - . Missed nursing care and italian nursing practice: preliminary findings of a
      consensus conference. In recent years in Italy there has been renewed interest in
      missed nursing care due to various factors, such as participation in the RANCARE
      project, with 28 European and non-EU countries, the opportunity to develop
      international exchanges, specific projects and field based research. We explored
      a range of ideas and processes, culminating in a conference designed to address
      specific issues relating to missed nursing care, in the Italian nursing practice.
      After a preliminary review of the literature on the psychometric properties of
      the available tools, with the intent of further deepening our understanding of
      the concept of missed nursing care, its implications for practice, management,
      education and research. After two days of presentations and discussions, the more
      than participating nurses agreed on a set of preliminary recommendations
      regarding missed nursing care and Italian nursing practice. This paper reports on
      the preliminary consensus findings from the conference.

PMID- 30303199
TI  - Quantifying the influence of the ion cloud on SAXS profiles of charged proteins.
AB  - Small-angle X-ray scattering (SAXS) is a popular experimental technique used to
      obtain structural information on biomolecules in solution. SAXS is sensitive to
      the overall electron density contrast between the biomolecule and the buffer,
      including contrast contributions from the hydration layer and the ion cloud. This
      property may be used advantageously to probe the properties of the ion cloud
      around charged biomolecules. However, in turn, contributions from the hydration
      layer and ion cloud may complicate the interpretation of the data, because these
      contributions must be modelled during structure validation and refinement. In
      this work, we quantified the influence of the ion cloud on SAXS curves of two
      charged proteins, bovine serum albumin (BSA) and glucose isomerase (GI), solvated
      in five different alkali chloride buffers of 100 mM or 500 mM concentrations. We
      compared three computational methods of varying physical detail, for deriving the
      ion cloud effect on the radius of gyration Rg of the proteins, namely (i)
      atomistic molecular dynamics simulations in conjunction with explicit-solvent
      SAXS calculations, (ii) non-linear Poisson-Boltzmann calculations, and (iii) a
      simple spherical model in conjunction with linearized Poisson-Boltzmann theory.
      The calculations for BSA are validated against experimental data. We find
      favorable agreement among the three computational methods and the experiment,
      suggesting that the influence of the ion cloud on Rg, as detected by SAXS, may be
      predicted with nearly analytic calculations. Our analysis further suggests that
      the ion cloud effect on Rg is dominated by the long-range distribution of the
      ions around the proteins, as described by Debye-Huckel theory, whereas the local
      salt structure near the protein surface plays a minor role.

PMID- 30303200
TI  - Monte Carlo simulation on the dynamics of a semi-flexible polymer in the presence
      of nanoparticles.
AB  - The dynamics of a semi-flexible polymer chain in the presence of periodically
      distributed nanoparticles is simulated by using off-lattice Monte Carlo
      simulations. For repulsive or weak attractive nanoparticles, the dynamics are
      slowed down monotonically by increasing the chain stiffness ktheta or decreasing
      the inter-particle distance d. For strong attractive nanoparticles, however, the
      dynamics show nonmonotonic behaviors with ktheta and d. An interesting result is
      that a stiff polymer may move faster than a flexible one. The underlying
      mechanism is that the nanoparticle's attraction is weakened by the chain
      stiffness. The nonmonotonic behavior of the polymer's dynamics with ktheta is
      explained by the competition between the weakening effect of the chain stiffness
      on the nanoparticle's attraction and the intrinsic effect of chain stiffness
      which reduces the dynamics of the polymer. In addition, the nonmonotonic behavior
      of the polymer's dynamics with d is explained by the competition between the
      nanoparticle-exchange motion of the polymer dominated at small d and the
      desorption-and-adsorption motion at large d. The excluded volume effect of the
      nanoparticles plays a more important role for stiffer polymers as the attraction
      of the nanoparticles is weakened by the chain stiffness.

PMID- 30303201
TI  - Multi-functional MnO2 nanomaterials for photo-activated applications by a plasma
      assisted fabrication route.
AB  - Supported MnO2-based nanomaterials were fabricated on fluorine-doped tin oxide
      substrates using plasma enhanced-chemical vapor deposition (PE-CVD) between 100 
      degrees C and 400  degrees C, starting from a fluorinated Mn(ii) diamine
      diketonate precursor. Growth experiments yielded beta-MnO2 with a hierarchical
      morphology tuneable from dendritic structures to quasi-1D nanosystems as a
      function of growth temperature, whose variation also enabled a concomitant
      tailoring of the system fluorine content, and of the optical absorption and band
      gap. Preliminary photocatalytic tests were aimed at the investigation of
      photoinduced hydrophilic (PH) and solid phase photocatalytic (PC) performances of
      the present nanomaterials, as well as at the photodegradation of Plasmocorinth B
      azo-dye aqueous solutions. The obtained findings highlighted an attractive system
      photoactivity even under visible light, finely tailored by fluorine content,
      morphological organization and optical properties of the prepared nanostructures.
      The results indicate that the synthesized MnO2 nanosystems have potential
      applications as advanced smart materials for anti-fogging/self-cleaning end uses
      and water purification.

PMID- 30303202
TI  - Kinetic pathways towards mass production of single crystalline stanene on
      topological insulator substrates.
AB  - As a highly appealing new member of the two-dimensional (2D) materials family,
      stanene was first epitaxially grown on a three-dimensional topological insulator
      of Bi2Te3; yet, to date, a standing challenge is to drastically improve the
      overall quality of such stanene overlayers for a wide range of potential
      applications in next-generation quantum devices. Here we use state-of-the-art
      first-principles approaches to explore the atomistic growth mechanisms of stanene
      on different Bi2Te3(111)-based substrates, with intriguing discoveries. We first
      show that, when grown on experimentally studied Te-terminated Bi2Te3, stanene
      would follow an unusual partial-layer-by-partial-layer growth mode, characterized
      by short-range repulsive pairwise interactions of the Sn adatoms; the resultant
      stanene overlayer is destined to contain undesirable grain boundaries. More
      importantly, we find that stanene growth on Bi2Te3(111) pre-covered with a Bi
      bilayer follows a highly desirable nucleation-and-growth mechanism, strongly
      favoring single crystalline stanene. We further show that both systems exhibit
      pronounced Rashba spin-orbit couplings, while the latter system also provides new
      opportunities for the potential realization of topological superconductivity in
      2D heterostructures. The novel kinetic pathways revealed here will be
      instrumental in achieving the mass production of high-quality stanene with
      emergent physical properties of technological significance.

PMID- 30303203
TI  - Multi-segmented CdS-Au nanorods for electrochemiluminescence bioanalysis.
AB  - In this study, we have developed a programmable electrochemiluminescence (ECL)
      system based on multi-segmented CdS-Au nanorod arrays with a sequential and
      highly tunable structure. The nanorod arrays were synthesized by an
      electrodeposition method using anodic aluminum oxide (AAO) as the template in
      which the Au and CdS segments were alternately electrodeposited. Compared to pure
      CdS nanorod arrays, multi-segmented CdS-Au nanorod arrays have showed a better
      ECL performance, which can be attributed to two factors: the favorable electron
      transfer and the surface plasma resonance (SPR) effect of the Au segment. On the
      one hand, we demonstrated that the Au segment can increase the charge transfer
      rate of CdS, which is beneficial for the ECL process because the generation of
      the radical state needs to accept electrons and then generate the radical state.
      On the other hand, the SPR of Au plasmon-induced local electromagnetic field
      enhancement can increase the radiative decay rate of CdS which makes the ECL
      process more efficient and lead to a higher ECL intensity. And also, an ECL
      sensor with multi-segmented CdS-Au nanorod arrays was constructed to detect
      prostate protein antigen (PSA). This study provides some basis for designing high
      performance ECL emission materials and the construction of biosensors.

PMID- 30303204
TI  - Development of a selective and highly sensitive fluorescence assay for nucleoside
      triphosphate diphosphohydrolase1 (NTPDase1, CD39).
AB  - Ecto-nucleoside triphosphate diphosphohydrolase1 (NTPDase1, CD39) is a major
      ectonucleotidase that hydrolyzes proinflammatory ATP via ADP to AMP, which is
      subsequently converted by ecto-5'-nucleotidase (CD73) to immunosuppressive
      adenosine. Activation of CD39 has potential for treating inflammatory diseases,
      while inhibition was suggested as a novel strategy for the immunotherapy of
      cancer. In the present study, we developed a selective and highly sensitive
      capillary electrophoresis (CE) assay using a novel fluorescent CD39 substrate, a
      fluorescein-labelled ATP (PSB-170621A) that is converted to its AMP derivative.
      To accelerate the assays, a two-directional (forward and reverse) CE system was
      implemented using 96-well plates, which is suitable for the screening of compound
      libraries (Z'-factor: 0.7). The detection limits for the forward and reverse
      operation were 11.7 and 2.00 pM, respectively, indicating a large enhancement in
      sensitivity as compared to previous methods (e.g. malachite-green assay: 1 000
      000-fold, CE-UV assay: 500 000-fold, fluorescence polarization immunoassay: 12
      500-fold). Enzyme kinetic studies at human CD39 revealed a Km value of 19.6 MUM,
      and a kcat value of 119 * 10-3 s-1 for PSB-170621A, which shows similar substrate
      properties as ATP (11.4 MUM and 82.5 * 10-3 s-1). The compound displayed similar
      properties at rat and mouse CD39. Subsequent docking studies into a homology
      model of human CD39 revealed a hydrophobic pocket that accommodates the
      fluorescein tag. PSB-170621A was found to be preferably hydrolyzed by CD39 as
      compared to other ectonucleotidases. The new assay was validated by performing
      inhibition assays with several standard CD39 inhibitors yielding results that
      were consonant with data using the natural substrates.

PMID- 30303205
TI  - Hyphenation of high-temperature liquid chromatography with high-pressure
      electrospray ionization for subcritical water LC-ESI-MS.
AB  - High-pressure electrospray ionization (HP-ESI) performed under super-atmospheric
      pressure allows a stable and efficient electrospray of pure aqueous and/or
      superheated solutions even under a MUL min-1 flow rate regime. In this paper, we
      report the direct coupling of the HP-ESI source to high-temperature liquid
      chromatography (HT-LC) operated at <=30 MUL min-1 flow rates. In addition to ESI,
      the ion source functions as a back-pressure regulator to keep the mobile phase in
      the liquid phase when the column is heated to >100  degrees C. Under an ion
      source pressure of 7 bar, the LC column can be operated up to 160  degrees C. LC
      is performed under isocratic elution, and besides the isothermal mode, the
      temperature of the column can also be programmed to increase the selectivity
      while keeping the ion source at a constant temperature. For a given solution flow
      rate, the analytical time can be shortened by increasing the column temperature.
      HT-LC-ESI-MS using pure water as the mobile phase with a capillary column is also
      demonstrated.

PMID- 30303206
TI  - Selective aerobic oxidation of alkyl aromatics on Bi2MoO6 nanoplates decorated
      with Pt nanoparticles under visible light irradiation.
AB  - Pt/Bi2MoO6 nanoplates are efficient photocatalysts for the selective oxidation of
      saturated C-H bonds in alkyl aromatics under visible light illumination using O2
      as an oxidant. This study opens a new window for direct C-H functionalization
      through the photocatalytic method based on cheap Bi2MoO6 semiconductor materials.

PMID- 30303207
TI  - Design of dispersant structures for preparing highly concentrated one-dimensional
      inorganic molecular chains from V2Se9 crystals.
AB  - We studied dispersants for exfoliating bulk V2Se9 into one dimensional chain
      units. V2Se9, with a negative zeta potential of -30.1 mV, was acidic and strongly
      anchored with the amine head of octadecylamine by charge transfer reaction. The
      steric hindrance by the octadecyl tail promoted the dispersion of V2Se9 to the
      nano level.

PMID- 30303208
TI  - C50Cl10, a planar aromatic fullerene. Computational study of 13C-NMR chemical
      shift anisotropy patterns and aromatic properties.
AB  - The isolated-pentagon-rule (IPR) is a prime determinant of fullerene
      stabilization accounting for the difficult isolation of hollow Cn (n < 60)
      species. In this connection, the isolation and structural characterization of D5h
      C50Cl10 as an IPR-violating fullerene are of interest owing to the study of
      factors providing further stability. Herein, we use DFT calculations to explore
      its aromatic behavior. In this connection the C50Cl10 structure is considered as
      a fullerene displaying a planar-aromatic character provided by the face-to-face
      disposition of two IPR structural motifs, mediated by ten exobonded sp3-carbons.
      In addition, the D5h-C50Br10 counterpart appears to be another promising
      structure as the target for explorative synthesis. Owing to the curvature of its
      IPR motif, an interesting variation in the 13C-NMR patterns relative to
      corannulene is described, where the relation between CI and CII signals is useful
      to evaluate the degree of the curvature of the pi-surface. The charge
      distribution of C50Cl10 reveals a more electron-deficient IPR dome in comparison
      to C60, envisaging an enhanced chemistry related to bare fullerenes. In addition,
      the -Cl and -Br exobonded atoms provide effective sigma-holes, suggesting such
      oblate fullerenes as interesting two-dimensional five-fold symmetric synthons
      useful for the formation of supramolecular species. Hence, an interesting
      chemistry and supramolecular array derivatives are potential applications to be
      further explored towards the development of novel nano-devices.

PMID- 30303209
TI  - Size exclusion effect in binary inclusion compounds of alpha-cyclodextrin.
AB  - The size exclusion of guests by alpha-cyclodextrin (aCD) in binary host-guest
      systems was observed to be a key structure-property relationship for the choice
      of this host as a receptor. For this, vapor sorption isotherms of water and
      volatile organic compounds were determined using dry aCD, which show an inclusion
      threshold by sorbate activity corresponding to a phase transition of guest (or
      water) inclusion. These phase transitions were also characterized using X-ray
      powder diffractograms. The analysis of these data shows that interaction of aCD
      with water does not differ much from that with organic compounds that can be
      included by aCD without water and therefore are water-mimicking as such. The
      inclusion and hydration Gibbs energies and composition of the saturated host
      guest clathrates were determined from sorption isotherms. The Gibbs energies of
      guest inclusion by solid aCD and its hydration characterize the guest-host and
      water-host affinity in the solid state. The correlation of the obtained inclusion
      parameters with that of guest size indicate the ban on the inclusion of volatile
      hydrophilic organic compounds with more than three carbon atoms and smaller
      molecules without hydrophilic groups. These data may be used for estimation of
      the relative ability of more hydrophobic guests to replace water and organic
      solvents in solid aCD. The observed inclusion of water and small hydrophilic
      molecules by solid aCD with phase transition gives an alternative insight into
      the role of water in activating the inclusion of more hydrophobic guests.
      Furthermore, the results show the extent to which aCD may be preferable in
      applications using water or other solvents.

PMID- 30303210
TI  - A unique metallic phase of H3S at high-pressure: sulfur in three different local
      environments.
AB  - We propose a new metallic phase (R3[combining macron]m, Z = 24) for H3S in a
      large pressure interval (~108-166 GPa) using an evolutionary crystal structure
      search algorithm combined with first-principles calculations. This structure
      consists of SH6, SH3 and S units which are connected through strong SH hydrogen
      bonds. It supports four-types of SH hydrogen-bonds that symmetrize at ~166 GPa.
      This is the only phase in the H-S family where sulfur exists in three different
      local environments. Sulfur in SH6 behaves as a cation, like in the SF6 molecule,
      whereas other sulfurs behave as anions. Hydrogens in SH6 behave like halogens
      (anions) whereas other hydrogens behave like alkalis (cations). The new structure
      has a substantially smaller DOS at the Fermi-level in comparison to earlier
      structures R3m and Im3[combining macron]m. This implies a lower superconducting
      temperature (TC) for the new phase and thus questions the validity of earlier
      high-TC explanations. We also find that S-H covalent bonds are different from the
      B-B bonds of MgB2.

PMID- 30303211
TI  - Comparing the reactivity of isomeric phosphinoferrocene nitrile and isocyanide in
      Pd(ii) complexes: synthesis of simple coordination compounds vs. preparation of P
      chelated insertion products and Fischer-type carbenes.
AB  - Isomeric phosphinoferrocene ligands, viz. 1'-(diphenylphosphino)-1-cyanoferrocene
      (1) and 1'-(diphenylphosphino)-1-isocyanoferrocene (2), show markedly different
      coordination behaviours. For instance, the reactions of 1 with [PdCl2(MeCN)2] and
      [(LNC)Pd(MU-Cl)]2 (LNC = [2-(dimethylamino-kappaN)methyl]phenyl-kappaC1) produced
      the "phosphine" complexes [PdCl2(1-kappaP)2] (7) and [(LNC)PdCl(1-kappaP)] (8),
      and the latter was converted into the coordination polymer [(LNC)Pd(MU(P,N)
      1)][SbF6] (9). Conversely, the reaction of 2 with [(LNC)Pd(MU-Cl)]2 involved
      coordination of the phosphine moiety and simultaneous insertion of the isocyanide
      group into the Pd-C bond, giving rise to the P,eta1-imidoyl complex
      [PdCl(Ph2PfcN[double bond, length as m-dash]CC6H4CH2NMe2-kappa3C,N,P)] (10; fc =
      ferrocene-1,1'-diyl). Compound 10 was further transformed into the Fischer
      carbene [PdCl(Ph2PfcN(Me)CC6H4CH2NMe2-kappa3P,C,N)][BF4] (11) by methylation with
      [Me3O][BF4]. The reactions of 2 with Pd-Me and Pd(eta3-allyl) precursors also led
      to imidoyl complexes [Pd(MU-Cl)(Ph2PfcN[double bond, length as m-dash]CR
      kappa2C,P)]2 (R = Me: 12, R = allyl: 15), which were cleaved with PPh3 into the
      corresponding monopalladium complexes [PdCl(PPh3)(Ph2PfcN[double bond, length as
      m-dash]CR-kappa2C,P)] (R = Me: 13, R = allyl: 16). The treatment of 12 and 15
      with thallium(i) acetylacetonate (acac) produced [Pd(acac-O,O')(Ph2PfcN[double
      bond, length as m-dash]CR-kappa2C,P)] (R = Me: 17, R = allyl: 18). Through proton
      transfer, these complexes reacted with Ph2PCH2CO2H, ultimately producing bis
      chelate complexes [Pd(Ph2PCH2CO2-kappa2O,P)(Ph2PfcN[double bond, length as m
      dash]CR)] (R = Me: 19, R = prop-1-enyl (sic!): 20). In addition, compound 13 was
      converted into the P-chelated carbene [PdCl(PPh3)(Ph2PfcN(Me)CMe-kappa2C,P)][BF4]
      (14). Compounds 10, 11, 13 and 14 were studied by cyclic voltammetry and by DFT
      computations.

PMID- 30303213
TI  - Dynamics and kinetics of the reaction OH + H2S -> H2O + SH on an accurate
      potential energy surface.
AB  - The dynamics and kinetics of the prototypical hydrogen abstraction reaction OH +
      H2S -> H2O + SH were studied using the quasi-classical trajectory approach on a
      new accurate ab initio potential energy surface (PES) for the ground electronic
      state. The PES was developed by fitting 82 680 ab initio points at the level of
      UCCSD(T)-F12a/aug-cc-pVTZ using the fundamental invariant-neural network method.
      On one hand, excitation of either the symmetric stretching mode or the asymmetric
      stretching mode of the reactant H2S almost equivalently enhances the reaction.
      The promotional effect of exciting the bending mode of H2S is not as strong as
      exciting the stretching modes while it increases with the collision energy. On
      the other hand, the calculated vibrational state distribution of the product H2O
      based on the normal mode analysis method agrees reasonably well with the earlier
      experimental result, which was rationalized by the underlying reaction
      mechanisms. In addition, the rate constants of the reaction have a non-Arrhenius
      temperature dependence.

PMID- 30303214
TI  - Long-lived triplet excited state in a platinum(ii) perylene monoimide complex.
AB  - We report the synthesis and solution based photophysical properties of a new
      Pt(ii)-terpyridine complex coupled to a perylene monoimide (PMI) chromophoric
      unit through an acetylene linkage. This structural arrangement resulted in
      quantitative quenching of the highly fluorescent PMI chromophore by introducing
      metal character into the lowest energy singlet state, thereby leading to the
      formation of a long-lived PMI-ligand localized triplet excited state (tau = 8.4
      MUs). Even though the phosphorescence from this triplet state was not observed,
      highly efficient quenching of this excited state by dissolved oxygen and the
      observation of singlet oxygen photoluminescence in the near-IR at 1270 nm
      initially pointed towards triplet excited state character. Additionally, the
      coincidence of the excited state absorbance difference spectra from the
      sensitized PMI ligand using a triplet donor and the Pt-PMI complex provided
      strong evidence for this triplet state assignment, which was further supported by
      TD-DFT calculations.

PMID- 30303217
TI  - Synthesis of complementary hierarchical structured Si/C composites with high Si
      content for lithium-ion batteries.
AB  - Si/C composites are considered as the most promising anode materials for next
      generation lithium-ion batteries (LIBs) due to their high specific capacity and
      low cost. However, the commercialized Si/C composites cannot maintain a Si
      content over 10 wt% for sustaining an acceptable cycle life. To achieve long-term
      cycle stability for Si/C composites with high Si content is still very
      challenging. Here, we report a rationally designed double-morphology Si/graphene
      (DMSiG) composite with a high Si content of 78 wt%, and prove its feasibility as
      a high performance anode material for LIBs. DMSiG composes of Si quantum-dot
      decorated graphene and mesoporous Si spheres with a complementary hierarchical
      structure. The graphene framework enhances the electronic conductivity,
      alleviates the aggregation of mesoporous Si spheres and provides space and
      flexibility to buffer the volume change during cycling. Mesoporous Si spheres
      contribute to a large reversible capacity and support the hierarchical
      architecture of DMSiG. The Si quantum-dots help to build firm connections between
      graphene and mesoporous Si spheres to avoid their separation during cycling.
      Coupling these features together, the DMSiG anode delivers a high reversible
      capacity of 1318 mA h g-1 at a current density of 500 mA g-1 and 684 mA h g-1 at
      2000 mA g-1.

PMID- 30303218
TI  - Two-step synthesis of hole structure bastnasite (RECO3F RE = Ce, La, Pr, Nd) sub
      microcrystals with tunable luminescence properties.
AB  - A two-step synthetic route using RE(OH)CO3 colloid spheres as the sacrificial
      template was designed to prepare monodisperse, pure bastnasite (RECO3F: RE = Ce,
      La, Pr, Nd) with a hole structure for the first time. A variety of morphologies,
      including jujube core-like, stacked nanoblocks, and stacked nanosheets were
      obtained through changing the ratio of reactants. The phase, structure, shapes,
      and photoluminescence properties of samples were characterized by X-ray
      diffraction (XRD), field-emission scanning electron microscopy (FE-SEM),
      transmission electron microscopy (TEM) and photoluminescence (PL) spectroscopy.
      The CeCO3F:Ln3+ (Ln = Tb, Eu, Dy) phosphors give green, yellow and blue emission,
      respectively, due to the f-f transitions of Ln3+ ions. Furthermore, the energy
      transfer from Ce3+ to Dy3+ and Tb3+ was described in detail.

PMID- 30303219
TI  - Stable-radicals increase the conductance and Seebeck coefficient of graphene
      nanoconstrictions.
AB  - Nanoscale thermoelectricity is an attractive target technology, because it can
      convert ambient heat into electricity for powering embedded devices in the
      internet of things. We demonstrate that the thermoelectric performance of
      graphene nanoconstrictions can be significantly enhanced by the presence of
      stable radical adsorbates, because radical molecules adsorbed on the graphene
      nanoconstrictions create singly-occupied orbitals in the vicinity of Fermi
      energy. This in turn leads to sharp features in their transmission functions
      close to Fermi energy, which increases the electrical conductance and Seebeck
      coefficient of the nanoconstrictions. This is a generic feature of radical
      adsorbates and can be employed in the design of new thermoelectric devices and
      materials.

PMID- 30303221
TI  - Cobalt complexes with hemilabile o-iminobenzoquinonate ligands: a novel example
      of redox-induced electron transfer.
AB  - The tetracoordinated square-planar CoIII complex (imSQC(O)Ph)CoIII(APC(O)Ph) (1)
      bearing a radical anion and the closed-shell o-amidophenolate forms of the
      functionalized o-aminophenol H2LC(O)Ph were synthesized. The intermediate spin
      state (SCo = 1) CoIII center was found for compound 1. The cyclic voltammogram of
      derivative 1 contains two oxidative processes and one reductive redox process as
      well as an additional multi-electron wave at high negative potentials above -2 V,
      which can involve both the ligand and metal center. One-electron oxidation of 1
      by silver triflate produces the [(imSQC(O)Ph)CoII(imQC(O)Ph)]OTf.2toluene (2)
      derivative with the trigonal prismatic coordination environment of the metal
      arising from the additional coordination of -C(O)Ph hemilabile groups. This is a
      first example of a trigonal prismatic coordination polyhedron in cobalt-based
      complexes featuring o-iminobenzoquinone ligands. The trigonal prismatic geometry
      achieved by the unique flexibility of the ligand allows metal-to-ligand redox
      induced electron transfer (RIET). Chemical oxidation of complex 1 promotes the
      reduction of CoIII to CoII in compound 2 due to the redox-active nature of o
      iminobenzoquinonate ligands. Remarkably, this is the first example of RIET in
      cobalt-based derivatives with this type of ligand. The oxidative states of the
      ligands and cobalt ion in both complexes were unequivocally established according
      to the X-ray data collection by using the utility of "metric oxidation state"
      (MOS). The spin states of the metal centers were unambiguously determined by
      density functional theory. The strong antiferromagnetic exchange via metal-ligand
      interactions is dominant in compounds 1 and 2, giving the doublet (S = 1/2) and
      triplet (S = 1) ground spin state, respectively.

PMID- 30303220
TI  - Copper(ii) complexes for cysteine detection using 19F magnetic resonance.
AB  - Cysteine plays an essential role in maintaining cellular redox homeostasis and
      perturbations in cysteine concentration are associated with cardiovascular
      disease, liver disease, and cancer. 19F MRI is a promising modality for detecting
      cysteine in biology due to its high tissue penetration and negligible biological
      background signal. Herein we report fluorinated macrocyclic copper complexes that
      display a 19F NMR/MRI turn-on response following reduction of the Cu(ii)
      complexes by cysteine. The reactivity with cysteine was studied by monitoring the
      appearance of a robust diamagnetic 19F signal following addition of cysteine in
      conjunction with UV-vis and EPR spectroscopies. Importantly, complexes with 
      CH2CF3 tags display good water solubility. Studies with this complex in HeLa
      cells demonstrate the applicability of these probes to detect cysteine in complex
      biological environments.

PMID- 30303224
TI  - The impact of substrate surface defects on the properties of two-dimensional van
      der Waals heterostructures.
AB  - The recent emergence of vertically stacked van der Waals (vdW) heterostructures
      provides new opportunities for these materials to be employed in a wide range of
      novel applications. Understanding the interlayer coupling in the stacking
      geometries of the heterostructures and its effect on the resultant material
      properties is particularly important for obtaining materials with desirable
      properties. Here, we report that the atomic bonding between stacked layers and
      thereby the interlayer properties of the vdW heterostructures can be well tuned
      by the substrate surface defects using WS2 flakes directly grown on graphene. We
      show that the defects of graphene have no significant effect on the crystal
      structure or the quality of the grown WS2 flakes; however, they have a strong
      influence on the interlayer interactions between stacked layers, thus affecting
      the layer deformability, thermal stability, and physical and electrical
      properties. Our experimental and computational investigations also reveal that
      WS2 flakes grown on graphene defects form covalent bonds with the underlying
      graphene via W atomic bridges (i.e., formation of larger overlapping hybrid
      orbitals), enabling these flakes to exhibit different intrinsic properties, such
      as higher conductivity and improved contact characteristics than heterostructures
      that have vdW interactions with graphene. This result emphasizes the importance
      of understanding the interlayer coupling in the stacking geometries and its
      correlation effect for designing desirable properties.

PMID- 30303225
TI  - Step-economical synthesis of 3-amido-2-quinolones by dendritic copper powder
      mediated one-pot reaction.
AB  - The one-pot protocol by the dendritic copper powder-mediated Knoevenagel
      condensation/annelation is delineated here for the synthesis of 3-amido-2
      quinolones. It is practical with moisture tolerance and easy setup, and is
      compatible with many functional groups under mild conditions. This method was
      applied for the preparation of the key intermediates of biologically relevant 3
      amido-2-quinolones.

PMID- 30303226
TI  - Three-dimensional hierarchical Ni3Se2 nanorod array as binder/carbon-free
      electrode for high-areal-capacity Na storage.
AB  - A three-dimensional hierarchical Ni3Se2 nanorod array (NA) grown in situ on foam
      Ni is the first to act as a carbon/binder-free electrode of SIBs via a one-step
      reversible conversion reaction. By a special decomposition-fusion process, the
      morphology and composition of the NA are regulated to obtain ultrahigh areal
      capacity, which is three times greater than that reported for other metal
      selenides.

PMID- 30303227
TI  - SSZ-70 borosilicate delamination without sonication: effect of framework topology
      on olefin epoxidation catalysis.
AB  - We report a scalable delamination procedure for a SSZ-70-framework layered
      zeolite precursor, which for the first time does not involve either sonication or
      long-chain surfactants. Our approach instead relies on the mild heating of
      layered zeolite precursor B-SSZ-70(P) in an aqueous solution containing Zn(NO3)2
      and tetrabutylammonium fluoride. Powder X-ray diffraction data are consistent
      with a loss of long-range order along the z-direction, while 29Si MAS NMR
      spectroscopy demonstrates preservation of the zeolite framework crystallinity
      during delamination. The resulting delaminated material, DZ-2, possesses 1.4-fold
      higher external surface area relative to the nondelaminated three-dimensional
      zeolite B-SSZ-70, based on N2 physisorption data at 77 K. DZ-2 was functionalized
      with cationic Ti heteroatoms to synthesize Ti-DZ-2 via exchange with framework B.
      Ti-DZ-2 contains isolated titanium centers in its crystalline framework, as shown
      by UV-Vis spectroscopy. The generality of the synthetic delamination approach and
      catalyst synthesis is demonstrated with the synthesis of delaminated material DZ
      3, which is derived from layered zeolite precursor ERB-1(P) with MWW framework
      topology. Upon catalytic testing for the epoxidation of 1-octene with
      ethylbenzene hydroperoxide as oxidant, under harsh tail-end conditions that
      deactivate amorphous Ti-silica-based catalysts, Ti-DZ-2 exhibits the highest per
      Ti-site activity, selectivity, and stability for 1-octene epoxidation of all
      catalysts investigated. This testing includes the prior benchmark delaminated
      zeolite catalyst in this area, Ti-UCB-4, which possesses similar external surface
      area to Ti-DZ-2 but requires sonication and long-chain surfactants for its
      synthesis. The synthesis of DZ-2 is the first example of an economical
      delamination of layered zeolite precursor SSZ-70(P) and opens up new doors to the
      development of delaminated zeolites as commercial catalysts.

PMID- 30303228
TI  - Synthesis of medium-sized (6-7-6) ring compounds by iron-catalyzed
      dehydrogenative C-H activation/annulation.
AB  - In this report, we have described a FeCl3-catalyzed process involving
      intramolecular annulation of o-phenoxy diarylacetylenes via hydroarylation to
      afford a series of biologically potent fused seven-membered (6-7-6) ring
      compounds under mild reaction conditions. This reaction was believed to proceed
      through Friedel-Crafts type sequential carbometallation followed by protonation
      to produce phenyldibenz[b,f]oxepines. This method was also extended to synthesize
      seven-membered rings that are fused with coumarins.

PMID- 30303229
TI  - Total synthesis, structural revision and biological evaluation of gamma-elemene
      type sesquiterpenes.
AB  - Total synthesis and absolute configuration confirmation of gamma-elemene-type
      sesquiterpenes, which possess vast potential for biological activities, was
      investigated based on a convergent synthetic strategy. A key intermediate with
      all functional groups of this family of natural products was accessed by an
      intermolecular aldol reaction and then an acetylation of a known ketone (12)
      derived from commercially available verbenone. The versatile intermediate can be
      easily transformed into structurally different gamma-elemene-type sesquiterpenes
      based on control of base-promoted cyclization manipulation in different solvents.
      The utility of this robust approach is illustrated by the first syntheses of
      elema-1,3,7(11),8-tetraen-8,12-lactam (4') and 8beta-methoxy-isogermafurenolide
      (6a), as well as the syntheses of elem-1,3,7,8-tetraen-8,12-olide (3) and
      hydroxyisogermafurenolide (5) in only 6 or 7 steps. In addition, the structure of
      the reported 5betaH-elem-1,3,7,8-tetraen-8,12-olide (1) was revised as elem
      1,3,7,8-tetraen-8,12-olide (3) by comparison of their identified datum, and the
      absolute configuration of elema-1,3,7(11),8-tetraen-8,12-lactam was confirmed as
      4'. Furthermore, the inhibitory effect of all synthesized natural compounds and
      their natural analogues on cancer cell proliferation was evaluated. Among them
      compounds 3, 4 and 4' were found to possess potent inhibitory activity against
      Kasumi-1 and Pfeiffer. Meanwhile, preliminary structure-activity relationships
      for these compounds are discussed.

PMID- 30303231
TI  - pi-Extended hexadeca-substituted cobalt phthalocyanine as an active layer for
      organic field-effect transistors.
AB  - Due to their flexibility and solution applicability, organic field-effect
      transistors (OFETs) are considered prominent candidates for application in
      flexible and low-cost devices. A soluble phthalocyaninato cobalt(ii) complex was
      designed and synthesized based on a hexadeca-substitution pattern by introducing
      peripheral phenylethynyl groups and non-peripheral n-butoxy groups. The cobalt
      phthalocyanine derivative was characterized using a wide range of spectroscopic
      and electrochemical methods, as well as single-crystal X-ray diffraction
      analysis. An OFET device was fabricated using a spin-coated film of soluble
      1,4,8,11,15,18,22,25-octakisbutoxy-2,3,9,10,16,17,23,24-octakis-ethynyl phenyl
      phthalocyaninato cobalt(ii) with a bottom-gate top-contact device configuration.
      The transfer and output characteristics were investigated to evaluate the charge
      carrier mobility. The mechanisms of the leakage current through the gate
      dielectric were also investigated, which revealed that the dominant leakage
      current mechanism is Fowler-Nordheim tunneling.

PMID- 30303232
TI  - Piezo-phototronic mediated enhanced photodetection characteristics of plasmonic
      Au-g-C3N4/CdS/ZnO based hybrid heterojunctions on a flexible platform.
AB  - We have studied the piezo-phototronic induced enhancement in the photo-response
      of CdS/ZnO heterojunctions attached with plasmonic Au nanoparticle loaded 2D
      graphitic carbon nitride (g-C3N4). The hybrid g-C3N4/CdS/ZnO heterojunction
      favours the charge carrier separation through the formation of a step-like band
      alignment. Furthermore, the integration of plasmonic Au loaded g-C3N4 nanosheets
      on the conventional CdS/ZnO heterojunction facilitates improved visible light
      absorption properties. The heterojunction device on a flexible platform under the
      application of a strain (~0.017%) exhibits ~102 times higher photoresponse over
      the control sample at a constant bias of ~2 V. The variation in the photo
      response under different bending conditions has been explained in terms of the
      improved charge transport through the modified energy bands at the interface of
      ZnO. The improved piezo-phototronic properties originated from the plasmonic
      properties of Au loaded g-C3N4 and the piezoelectric characteristics of c-axis
      oriented ZnO films may be used for future flexible photonic devices.

PMID- 30303233
TI  - Barium-promoted hydrothermal stability of monolithic Cu/BEA catalyst for NH3-SCR.
AB  - As a promising candidate for NOx elimination from the emission of diesel engines,
      the enhancement effect of Ba on the hydrothermal stability of cordierite
      supported CuBa/BEA at 600  degrees C for 48 h was investigated by XRD, NH3-TPD,
      H2-TPR, XPS, EPR, TEM and in situ DRIFTS. Different properties and amounts of
      active species are significant factors contributing to the enhanced hydrothermal
      stability of CuBa/BEA-HT. CuBa/BEA-HT has more Cu2+/Cu+ redox-couples and
      stronger interactions than Cu/BEA-HT, indicating an excellent redox property of
      the active species in CuBa/BEA-HT. The better redox property of CuBa/BEA-HT
      produces more nitrates that easily participate in the NH3-SCR reaction, which
      enhances the low-temperature activity. Furthermore, as observed from EPR and H2
      TPR, the appearance of more isolated Cu2+ species and fewer CuO species also
      contribute to the higher hydrothermal stability of CuBa/BEA-HT.

PMID- 30303234
TI  - Regioselective synthesis of isoxazole and 1,2,4-oxadiazole-derived phosphonates
      via [3 + 2] cycloaddition.
AB  - The results of the study on reactions of halogenoximes bearing (protected)
      functional groups or fluorinated substituents with various phosphorus-containing
      dipolarophiles are described. To control the regioselectivity of the reaction,
      vinylphosphonates bearing a leaving group (i.e. bromine or dialkylamino group) in
      the alpha or beta position were used; 3,5- and 3,4-disubstituted isoxazoles were
      obtained in 47-80% and 63-75% yields, respectively. The reaction was also
      effective for the parent vinyl phosphonate and cyanophosphonate; in this case,
      the corresponding isoxazoline- and 1,2,4-oxadiazole-derived phosphonates were
      isolated in 55-69% and 34-73% yields, respectively. The utility of the products
      obtained was demonstrated by the preparation of direct conformationally
      restricted analogues of phosphohistidine.

PMID- 30303235
TI  - Electrochemical study of specially designed graphene-Fe3O4-polyaniline
      nanocomposite as a high-performance anode for lithium-ion battery.
AB  - In this work, an anode material with improved thermal stability, charge capacity,
      charge capacity retention, energy density, cyclic performance, operation safety,
      reversible capacity, and rate capability was synthesized for battery
      applications. The graphene-magnetite-polyaniline (Gr-Fe3O4-PANI) nanocomposites
      (NCs) are believed to deliver outstanding performance owing to the collective
      effect of the layered graphene (Gr) and magnetite (Fe3O4) hollow rods (HRs), as
      well as the better conductivity of polyaniline (PANI). The Gr-Fe3O4-PANI NCs
      easily enable the insertion and deinsertion of Li+, the passage of ions in the
      electrode, fast kinetics of Li+, and low volume expansion. Gr-Fe3O4-PANI NC was
      prepared by polymerizing aniline in the presence of already prepared Fe3O4 HRs,
      then dispersing in Gr. Fe3O4 HRs were synthesized by a hydrothermal route.
      Electrochemical properties were investigated by galvanostatic charge-discharge
      analysis and cyclic voltammetry. A lithium-ion battery (LIB) based on the Gr
      Fe3O4-PANI exhibited a superior reversible current capacity of 1214 mA h g-1,
      excellent power capability, low volume expansion, high cycling stability and
      99.6% coulombic efficiency over 250 cycles.

PMID- 30303237
TI  - Dynamic Diels-Alder reactions of maleimide-furan amphiphiles and their
      fluorescence ON/OFF behaviours.
AB  - The occurrence of dynamic covalent reactions only requires relatively low
      activation energy, which allows both the forward and reverse reactions to proceed
      under mild conditions. Here, we report the design and synthesis of amphiphilic
      maleimide-furan adducts, where hydrophobic maleimide-based and hydrophilic furan
      based moieties were connected by reversible dynamic covalent bonds. The Diels
      Alder addition reactions of maleimide-furan adducts are simple, efficient, clean,
      and reversible without catalysts and side reactions, and occur under mild
      conditions. Single crystal X-ray diffraction revealed that the length of the
      dynamic covalent bonds is 1.56 A, which is longer and weaker than for normal
      covalent bonds. The cleavage and reformation process of the dynamic covalent
      bonds was monitored by 1H NMR and fluorescence spectroscopy. 1H NMR spectroscopy
      revealed that the furan moieties of these new maleimide-furan amphiphiles can be
      exchanged in mixing systems due to dynamic Diels-Alder reactions; thus, two new
      maleimide-furan compounds can be transformed into each other. The maleimide-furan
      amphiphiles displayed reversible fluorescence ON/OFF behaviours and interesting H
      bonding driven supramolecular assembly.

PMID- 30303242
TI  - Reply to: Beyond Tube-Feeding: Relationship-Centered, Comfort Care for
      Individuals with Eating Challenges in Dementia.

PMID- 30303240
TI  - Realizing enhanced luminescence of silver nanocluster-peptide soft hydrogels by
      PEI reinforcement.
AB  - Metal nanoclusters (NCs) are a new type of fluorescent nanomaterial composed of
      several to several tens of metal ions or atoms with a wide range of applications
      in the fields of catalysis, optics, and biomedicine. However, fluorescence
      quenching when existing as individuals in aqueous solutions greatly limits their
      applications. In this study, six-core Ag(i) NCs (Ag6-NCs) were interacted with
      peptides (DD-5) in water to form soft hydrogels with the aggregation-induced
      emission (AIE) of Ag6-NCs. The introduction of polyethyleneimine (PEI) into the
      Ag6-NCs/DD-5 hydrogel succeeded in further enhancing the fluorescence intensity.
      This dual-AIE behavior of the Ag6-NCs/DD-5/PEI hydrogels is mainly ascribed to
      the strong hydrogen bonding among the carboxyl groups of Ag6, those of DD-5 and
      the amino groups of PEI, which effectively restricted intramolecular vibration of
      the capping ligands on the Ag6-NCs. Moreover, the addition of PEI can effectively
      promote the gelation speed of Ag6-NCs/DD-5 and act as a physical cross-linker,
      leading to an increase of the mechanical strength of the hydrogel. This work
      opens a new pathway for the fabrication of smart composite materials with
      multiple functions, which show a variety of applications such as
      chemical/biosensing and bioimaging.

PMID- 30303243
TI  - Beyond Tube-Feeding: Relationship-Centered, Comfort Care for Individuals with
      Eating Challenges in Dementia.

PMID- 30303244
TI  - Cancer patients' experiences with urgent referrals to cancer patient pathways.
AB  - OBJECTIVE: We aimed to explore whether cancer patients urgently referred to a
      cancer patient pathway (CPP) (CPP referred) by a general practitioner report
      experiences of pre-diagnosis cancer care differently than patients not referred
      to a CPP (non-CPP referred). METHODS: Data were collected from cross-sectional
      questionnaire surveys among cancer patients and their GPs and linked to National
      registries. Poisson regression was used to generate adjusted prevalence ratios
      (PR) to compare reported experiences. RESULTS: The study included 2,256
      individuals. CPP referred patients reported more positive overall experiences of
      the pre-diagnosis phase (p < 0.001). Overall, CPP referred patients were 21% more
      likely than non-CPP referred patients to report a positive experience after
      adjustment for case-mix, comorbidity, disposable household income and educational
      level (PR = 1.21 [95% CI: 1.11-1.30]). The difference decreased to 14% when
      adjusted for Quality Deviations (PR = 1.14 [95% CI: 1.06-1.23]) and to 11% when
      adjusted for diagnostic interval (PR = 1.11 [95% CI: 1.02-1.20]). CONCLUSION: Our
      findings suggest that CPP referred cancer patients have better experiences of pre
      diagnosis cancer care compared to non-CPP referred patients. A substantial part
      of the difference could be attributed to shorter diagnostic intervals and/or the
      absence of quality deviations among CPP patients, which reveals the potential for
      generally improving cancer patients' experiences by seamless and optimised
      diagnostic pathways.

PMID- 30303245
TI  - Antiplasmodial activity and cytotoxicity, isolation of active alkaloids, and
      dereplication of Xylopia sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS.
AB  - OBJECTIVES: To assess the antiplasmodial activity of the ethanol extract of
      Xylopia sericea leaves, Annonaceae, often associated with antimalarial use and to
      perform a bioguided isolation of active compounds. METHODS: Dereplication of
      ethanol extract by the UPLC-DAD-ESI-MS/MS technique allowed the identification of
      the major constituents, isolation and identification of alkaloids. The
      antiplasmodial and cytotoxic activity of the extract, fractions and isolated
      compounds was evaluated against the chloroquine-resistant W2 strain Plasmodium
      falciparum and HepG2 cells, respectively. KEY FINDINGS: Ethanol extract showed
      high reduction of parasitemia as well as moderate cytotoxicity (86.5 +/- 3.0%
      growth inhibition at 50 MUg/ml and CC50 72.1 +/- 5.1 MUg/ml, respectively). A
      total of eight flavonoids were identified, and two aporphine alkaloids, anonaine
      and O-methylmoschatoline, were isolated. Anonaine disclosed significant
      antiplasmodial effect and moderate cytotoxicity (IC50 23.2 +/- 2.7 MUg/ml, CC50
      38.3 +/- 2.3 MUg/ml, SI 1.6) while O-methylmoschatoline was not active against P.
      falciparum and showed a low cytotoxicity (33.5 +/- 1.9% growth inhibition at 50
      MUg/ml, CC50 274.4 +/- 0.5 MUg/ml). CONCLUSIONS: Characterization of Xylopia
      sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS as well as its
      antiplasmodial activity and the occurrence of anonaine and O-methylmoschatoline
      in this Xylopia species are reported by the first time.

PMID- 30303246
TI  - IL8 and IL17A polymorphisms associated with multibacillary leprosy and reaction
      type 1 in a mixed population from southern Brazil.
AB  - We evaluated the influence of the IL8 T-738A (nonidentified rs), IL8 T-353A
      (rs4073), IL17A G197A (rs2275913), and IL17F T7488C (rs763780) single-nucleotide
      polymorphisms on leprosy. The AA genotype of IL8 T-353A was observed as a risk
      factor for multibacillary leprosy, regardless of gender and age-of-onset of
      disease, considering the recessive model (OR, 3.8; 95% CI, 1.1-13.5; P, 0.023).
      Furthermore, the AA genotype of IL17A G197A was associated with leprosy type 1
      reaction (OR, 2.4; 95% CI, 1.1-5.1; P, 0.026) when compared to the group without
      reaction, which was adjusted for gender and age-of-onset of disease by the model
      log additive. These results indicate association of IL8 and IL17A polymorphisms
      with the progression to multibacillary leprosy and with the type 1 reaction,
      respectively.

PMID- 30303248
TI  - Special Issue: Abstracts of the ISPD 22nd International Conference on Prenatal
      Diagnosis and Therapy, Antwerp, Belgium, 8-11 July 2018.

PMID- 30303247
TI  - Inferior vena cava assessment can predict contrast-induced nephropathy in
      patients undergoing cardiac catheterization: A single-center prospective study.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) following cardiac catheterization
      remains a considerable clinic challenge. Volume status is very important in the
      development of CIN. It can be assessed noninvasively by measuring inferior vena
      cava (IVC) diameters. The aim of this study was to assess whether IVC can be used
      for prediction of CIN in patient undergoing cardiac catheterization. METHODS: A
      total of 269 patients undergoing cardiac catheterization were prospectively
      enrolled in this study. IVC inspiratory and expiratory diameters were measured by
      transthoracic echocardiography. Caval index was calculated as the percentage
      decrease in the IVC diameter during respiration. CIN was defined as a >=0.5 mg/dL
      and/or a >=25% increase in serum creatinine within 72 hour post-procedure.
      RESULTS: Contrast-induced nephropathy developed in 46 (17.1%) patients after
      cardiac catheterization. Caval index was significantly higher in patients with
      CIN than in patients without CIN (47% [40-64] vs 35% [26-50], P < 0.001). In
      addition, the used contrast volume (145 [90-217] vs 70 [60-100], P < 0.001) and
      the frequency of percutaneous coronary intervention (50% vs 17.9%, P < 0.001)
      were significantly higher in patients with CIN than in patients without CIN. In
      receiver operating characteristic (ROC) curve analysis, caval index >= 41%
      predicted CIN with a specificity of 69% and sensitivity of 72%. Multivariate
      analysis indicated that caval index >= 41% was an independent predictor of post
      procedural CIN development (OR: 3.367, 95% CI: 1.574-7.203, P = 0.002).
      CONCLUSIONS: Caval index, a simple and noninvasive echocardiographic marker, is
      an independent predictor of post-procedural CIN development in patients
      undergoing cardiac catheterization.

PMID- 30303249
TI  - Nitrous oxide effluxes from plants as a potentially important source to the
      atmosphere.
AB  - The global budget for nitrous oxide (N2 O), an important greenhouse gas and
      probably dominant ozone-depleting substance emitted in the 21st century, is far
      from being fully understood. Cycling of N2 O in terrestrial ecosystems has
      traditionally exclusively focused on gas exchange between the soil surface
      (nitrification-denitrification processes) and the atmosphere. Terrestrial
      vegetation has not been considered in the global budget so far, even though
      plants are known to release N2 O. Here, we report the N2 O emission rates of 32
      plant species from 22 different families measured under controlled laboratory
      conditions. Furthermore, the first isotopocule values (delta15 N, delta18 O and
      delta15 Nsp ) of N2 O emitted from plants were determined. A robust relationship
      established between N2 O emission and CO2 respiration rates, which did not alter
      significantly over a broad range of changing environmental conditions, was used
      to quantify plant-derived emissions on an ecosystem scale. Stable isotope
      measurements (delta15 N, delta18 O and delta15 Nsp ) of N2 O emitted by plants
      clearly show that the dual isotopocule fingerprint of plant-derived N2 O differs
      from that of currently known microbial or chemical processes. Our work suggests
      that vegetation is a natural source of N2 O in the environment with a large
      fraction released by a hitherto unrecognized process.

PMID- 30303251
TI  - Social relationship coping efficacy: A new construct in understanding social
      support and close personal relationships in persons with cancer.
AB  - OBJECTIVE: Social relationship coping efficacy (SRCE) is the confidence to engage
      in behaviors that can maintain or enhance close social relationships in the
      context of illness. This study focused on psychometric analyses of the SRCE scale
      and its role in maintaining or enhancing personal relationships, social support,
      and quality of life (QOL). METHOD: A mixed diagnosis sample (N = 151) of cancer
      patients completed a variety of measures: physical debilitation, received
      emotional and instrumental support, SRCE, and QOL. RESULTS: The SRCE scale is a
      10-item, one-factor, internally reliable (alpha = 0.965) measure with strong
      concurrent validity in relation to measures of social support. SRCE fully
      mediated the relationship between physical debilitation and both instrumental and
      emotional received support. SRCE also was directly related to both social/family
      well-being and psychological distress, and this relationship was also partially
      mediated by social support. CONCLUSIONS: The results corroborated that SRCE might
      account for changes in both instrumental and emotional support. Also, the direct
      and indirect relationship (mediated by social support) of SRCE with both
      social/family well-being and distress indicated that interventions to increase
      SRCE with those at risk for social support loss may bolster social support in
      personal relationships as well as enhance emotional well-being and quality of
      life.

PMID- 30303252
TI  - Onychomycosis caused by Scopulariopsis brevicaulis: The third documented case in
      Japan.

PMID- 30303253
TI  - Laser interference-based technique for dynamic measurement of single cell
      deformation manipulated by optical tweezers.
AB  - A laser interference-based method was proposed to measure the deformation
      response of cell manipulated by optical tweezers. This method was implemented
      experimentally by integrating a laser illuminating system and optical tweezers
      with an inverted microscope. Interference fringes generated by the transmitted
      and reflected lights were recorded by a complementary metal oxide semiconductor
      camera. From the acquired images, cell height was calculated and cell morphology
      was constructed. To further validate this method, the morphological analyses of
      HeLa cells were performed in static state and during detachment process.
      Subsequently, the dynamic deformation responses of red blood cells were measured
      during manipulation with optical tweezers. Collectively, this laser interference
      based method precludes the requirement of complex optical alignment, allows easy
      integration with optical tweezers, and enables dynamic measurement of cell
      deformation response by using a conventional inverted microscope.

PMID- 30303254
TI  - Identification of candidates for PFO closure in the echocardiography laboratory.
AB  - A patent foramen ovale (PFO) is implicated in several pathologic processes,
      including that of cryptogenic stroke (cCVA). Recent trials identify "high-risk"
      PFOs in patients with cCVA as likely to benefit from percutaneous closure. The
      younger the patient (<60 years old) the more likely a PFO may be attributable to
      the cCVA. The RoPE Score index helps determine the likelihood that an existing
      PFO is related to a cCVA. This may help guide the clinician and patient when
      contemplating percutaneous PFO closure. When evaluating a patient for possible
      percutaneous closure, one should identify the CVA as a typical ischemic type
      stroke. In order to "rule-out" other causes of CVA, imaging of the intracranial
      arteries, cervical, and aortic arch vessels should be performed. Small vessel
      disease or a lacunar-type infarct should be excluded. To rule out atrial
      fibrillation, prolonged monitoring should be performed. An index has been
      developed to determine the probability that a PFO is the causative etiology and
      calculates the risk of recurrence. This may help guide the clinician and patient
      in the decision for PFO closure. In addition, one should consider a work-up for a
      hypercoagulable state. We will obtain an ultrasound of the lower extremities or
      consider deep pelvic vein thrombosis (prolonged sitting or malignancy). If the
      closure is to be performed, the Food and Drug Administration (FDA) has approved
      the Amplatzer PFO Occluder and the GORE Cardioform Septal Occluder for
      percutaneous closure. These devices are both approved in patients predominately
      between ages 18 and 60 years with a cCVA due to presumed paradoxical embolism as
      verified by a neurologist and cardiologist and when other causes of ischemic CVA
      have been excluded. "High-risk" PFOs appear to achieve the most potential benefit
      from percutaneous closure.

PMID- 30303255
TI  - Agrowastes utilization by Raoultella ornithinolytica for optimal extracellular
      peroxidase activity.
AB  - The industrial applications and prospects of microbial peroxidase are on the
      upwards trend, thus necessitating the search for sources with high turnaround
      time. Actinobacterial species have been a major source of peroxidase for the
      obvious reasons of having robust metabolite expression capabilities. However,
      other bacteria species have been underexplored for peroxidase production, hence
      the motivation for the investigation into the peroxidase production potential of
      Raoultella ornithinolytica OKOH-1 (KX640917). The bacteria expressed optimum
      specific peroxidase activity of 16.48 +/- 0.89 U mg-1 , which is higher than
      those previously reported. The optimal fermentation conditions were pH 5 (3.44 +/
      0.64 U mL-1 ), incubation temperature of 35  degrees C (5.25 +/- 0.00 U mL-1 ),
      and agitation speed of 150 rpm (9.45 +/- 2.57 U mL-1 ), with guaiacol and
      ammonium chloride as the best inducer and nitrogen supplement, respectively. On
      valorization of agrowastes as a sole carbon source for the secretion of
      peroxidase, sawdust gave the best peroxidase yield (15.21 +/- 2.48 U mg-1 ) under
      solid-state fermentation. Also, a nonperoxide-dependent enzyme activity, which
      suggests probable laccase activity, was observed. The ability of the bacteria to
      utilize agrowastes is highly economical and as well a suitable waste management
      strategy. Consequently, R. ornithinolytica OKOH-1 is a promising industrial
      strain with dexterity for enhanced peroxidase production.

PMID- 30303256
TI  - Identification of genetic risk factors of aggressive periodontitis using
      genomewide association studies in association with those of chronic
      periodontitis.
AB  - To identify the genetic risk factors for aggressive periodontitis (AgP), it is
      important to understand the progression and pathogenesis of AgP. The purpose of
      this review was to summarize the genetic risk factors for AgP identified through
      a case-control genomewide association study (GWAS) and replication study. The
      initial studies to identify novel AgP risk factors were potentially biased
      because they relied on previous studies. To overcome this kind of issue, an
      unbiased GWAS strategy was introduced to identify genetic risk factors for
      various diseases. Currently, three genes glycosyltransferase 6 domain containing
      1 (GLT6D1), defensin alpha1 and alpha3 (DEFA1A3), and sialic acid-binding Ig-like
      lectin 5 (SIGLEC5) that reach the threshold for genomewide significance have been
      identified as genetic risk factors for AgP through a case-control GWAS.

PMID- 30303258
TI  - Elevated levels of interleukin-33 are associated with allergic and eosinophilic
      asthma.
AB  - : IL-33 is a recently discovered cytokine which plays an important role in asthma
      pathogenesis. AIM: to evaluate serum IL-33 in patients with asthma and healthy
      controls, and to evaluate the association of IL-33 with different asthma
      phenotypes. METHODS: Patients with asthma (n=115) and healthy subjects (n=85)
      were included in the study. Subjects with asthma were divided into groups
      according to their phenotype: allergic/non-allergic, eosinophilic/non
      eosinophilic, obese/non-obese and severity according to GINA (mild, moderate,
      severe). The concentration of IL-33 in serum was measured by standardized enzyme
      linked immunosorbent assay. RESULTS: The level of IL-33 was significantly higher
      in patients with asthma when compared to healthy subjects (672.73+/-104.47 pg/mL
      versus 268.52+/-27.56 pg/mL, p<0.05). IL-33 was also higher in the allergic
      asthma group patients when compared to non-allergic asthmatics (844.61+/-152.08
      pg/mL versus 369.56+/-77.94 pg/mL, p<0.05). There was a significantly higher
      serum IL-33 level in the eosinophilic asthma group when compared to the group of
      non-eosinophilic asthma patients (1001.10+/-199.11 pg/mL versus 337.49+/-72.68
      pg/mL, p<0.01). We did not find a significant difference in serum IL-33 level
      between different asthma severity groups, obese and non-obese asthmatics.
      CONCLUSION: IL-33 is increased in asthma patients, particularly in some
      phenotypes: allergic asthma and eosinophilic asthma. This article is protected by
      copyright. All rights reserved.

PMID- 30303259
TI  - On the reconceptualization of Alzheimer's disease.
AB  - In the hope of future treatments to prevent or slow down the disease, there is a
      strong movement towards an ever-earlier detection of Alzheimer's disease (AD). In
      conjunction with scientific developments, this has prompted a reconceptualization
      of AD, as a slowly progressive pathological process with a long asymptomatic
      phase. New concepts such as 'preclinical' and 'prodromal' AD have been
      introduced, raising a number of conceptual and ethical questions. We evaluate
      whether these new concepts are theoretically defensible, in light of theories of
      health and disease, and whether they should be understood as disease or as an at
      risk state. We introduce a pragmatic view on disease concepts and argue that an
      evaluation of the reconceptualization of AD should also take its aims and effects
      into account, and assess their ethical acceptability. The reconceptualization of
      AD is useful to coordinate research into preventive strategies, and may
      potentially benefit future patients. However, in the short term, early detection
      and labelling of 'preclinical AD' can potentially harm people. Since there is no
      treatment available and the predictive value is unclear, it may only create a
      group of 'patients-in-waiting' who may suffer from anxiety, uncertainty and
      stigmatization, but will never actually develop dementia. We conclude that only
      if the promise of preventive medication materializes, will the
      reconceptualization of AD turn out unequivocally to be for the better. Otherwise,
      the reconceptualization may do more harm than good.

PMID- 30303261
TI  - Embryo donation or embryo adoption? Conceptual and normative issues.
AB  - A central question in the ethical debate on the practice of relinquishing in
      vitro fertilization surplus embryos for family building is whether we ought to
      think of it more in terms of donating these embryos or in terms of having them
      adopted. Deciding between these two alternatives is more than a matter of mere
      terminology. It has an impact on normative questions, e.g., on the question of
      what criteria for parent selection ought to be applied to the recipients of the
      embryos, and on the moral evaluation of the act of 'donating' the embryo or
      'having it adopted'. In this article, I defend the view that we should
      conceptualize the relinquishment of spare embryos according to the adoption
      model, not as a donation. Section 2 sketches the outline of the argument by
      making clear how we may ground a defense of the adoption model in a theory of
      parental responsibility without implicitly elevating the moral status of the
      embryo. Section 3 contains a preliminary defense of the adoption model that draws
      on geneticism as what seems to me the most persuasive theory of parental
      responsibility. In section 4, I examine three objections to geneticism and either
      rebut them or, insofar as they are justified, try to accommodate them into my
      view. In section 5, I point out some features that distinguish embryo adoption
      from the adoption of (born) children. I contend, however, that these differences
      are compatible with the adoption model. Section 6 is concerned with the normative
      ramifications of this view.

PMID- 30303260
TI  - Does an integrated outreach intervention targeting multiple stages of early
      psychosis improve the identification of individuals at clinical high risk?
AB  - AIMS: To explore the impact of a targeted case identification intervention, with
      training and education regarding first-episode psychosis and clinical high-risk
      syndromes, on the referral and identification of those at high risk. METHODS:
      Using a historical control design, referral information from pre-intervention and
      post-intervention periods was collected via administrative data and clinician
      notes from a catchment-based early psychosis service. RESULTS: A significant
      increase in the number of referrals sent to the service's clinical high-risk unit
      was observed following the intervention (P = 0.01). The proportion of referrals
      eligible was significantly higher post-intervention (P = 0.03), with the majority
      (26/44, 59.1%) referred via the first-episode psychosis service unit.
      CONCLUSIONS: An integrated outreach intervention for both first-episode psychosis
      and the clinical high-risk state was effective in increasing referrals of
      eligible cases to the service's at-risk unit. Rather than being stage-specific,
      targeted case identification strategies and service integration should span
      across the early stages of psychosis.

PMID- 30303262
TI  - Clients' experience of change: An exploration of the influence of reformulation
      tools in cognitive analytic therapy.
AB  - Case formulation is considered important in both the development of the
      therapeutic relationship and in starting the process of therapeutic change.
      Cognitive analytic therapy (CAT) describes the developmental origins and
      maintenance of a client's problems in both written (reformulation letter) and
      diagrammatic form (sequential diagrammatic reformulation). This study aimed to
      investigate the effects of these reformulation tools on insight and symptom
      change. A small-N repeated measures design was employed with quantitative and
      qualitative measures collected from six therapist/client dyads. Participating
      therapists kept a record of their delivery of CAT reformulation tools.
      Participating clients completed the insight subscale of the Self-Reflection and
      Insight Scale every fourth session and the Clinical Outcomes in Routine
      Evaluation-10 every session. Qualitative data from client change interviews
      regarding their experiences of CAT and attributions of change was explored using
      template analysis. Participants demonstrated improvements (symptom reduction and
      insight increases) over the course of the intervention. Administration of
      reformulation tools did not consistently result in significant changes on insight
      and symptom measures. However, the tools were identified by participants as
      leading to insight and emotional change within the context of a good therapeutic
      relationship. These findings suggest that a genuine therapeutic relationship is
      an important change mechanism operating through, and strengthened by, CAT
      specific tools.

PMID- 30303263
TI  - Identification of Duchenne/Becker muscular dystrophy mosaic carriers through a
      combined DNA/RNA analysis.
AB  - OBJECTIVE: The Duchenne/Becker muscular dystrophy (DMD) carrier screening
      includes the evaluation of mutations in DMD gene, and the most widely used
      analysis is the multiplex ligation-dependent probe amplification (MLPA) for the
      DMD deletions/duplications detection. The high frequency of de novo mutations
      permits to estimate a risk up to 20% of mosaicisms for mothers of sporadic DMD
      children. The purpose of this study is to evaluate alternative analytical
      strategy for the detection of mosaics carrier women, in order to improve the
      recurrence risk estimation. METHOD: Different DNA and RNA analyses were conducted
      on samples from a woman that conceived a DMD fetus without previous family
      history of dystrophynopathy. RESULTS: Standard MLPA analysis failed to identify
      mosaicism, even if MLPA doses suggested it. Electrophoresis and direct sequencing
      conducted on RNA permitted to detect two different amplicons of cDNAs,
      demonstrating the presence of somatic mosaicism. Subsequent detection of a second
      affected fetus confirmed the mosaic status on the mother. CONCLUSION: The
      implementation of RNA analysis in diagnostic algorithm can increase the
      sensitivity of carrier test for mothers of sporadic affected patients, permitting
      detection of mosaic status. A revision of analytical guidelines is needed in
      order to improve the recurrence risk estimation and support prenatal genetic
      counseling.

PMID- 30303264
TI  - Autophagy gene ATG5 knockdown upregulates apoptotic cell death during Candida
      albicans infection in human vaginal epithelial cells.
AB  - PROBLEM: Candida albicans infection induces damage in host cells that results in
      the activation of cell death pathways such as apoptosis and necrosis. Autophagy
      acts as a pro-survival mechanism during various infections and has cross talks
      with apoptosis. The objective of our study was to delineate the effect of
      autophagy knockdown in human vaginal epithelial cells (VECs) during Candida
      infection-induced apoptosis. METHOD OF STUDY: We overexpressed wild-type or
      mutant form of autophagy-related gene 5 (ATG5) in human VECs and determined the
      levels of autophagy and lysosome marker genes upon C. albicans infection. We
      analyzed the expression of apoptosis and necrosis markers using confocal
      microscopy and flow cytometry. RESULTS: Mutant ATG5 overexpressing VECs were
      unable to form Atg5-Atg12 complex, which is required for functional autophagy
      pathway. Upon Candida albicans infection, wild-type ATG5 overexpressing cells
      showed upregulation of autophagy marker genes, ATG5, LC3-I, LC3-II, and LAMP-1.
      Mutant ATG5 overexpressing cells could not upregulate LC3-II and LAMP-1
      expression, indicating a defective autophagy pathway. Confocal microscopy and
      flow cytometry results revealed that wild-type ATG5 overexpressing VECs showed
      significantly lower number of apoptotic and necrotic cells as compared to mutant
      ATG5 overexpressing cells. CONCLUSION: Vaginal epithelial cells with active
      autophagy were able to survive the damage caused by C. albicans infection,
      whereas those with defective autophagy succumbed to the infection. This suggests
      that autophagy plays a critical role in human VECs survival during C. albicans
      infection.

PMID- 30303265
TI  - Negligible impact of birth on renal function and drug metabolism.
AB  - BACKGROUND: Transition from the intrauterine to the extrauterine environment in
      neonates is associated with major changes in blood flow and oxygenation with
      consequent increases in metabolic functions. The additional impact of birth on
      renal function and drug metabolism above that predicted by postmenstrual age and
      allometry is uncertain. Increased clearance at birth could reduce analgesic
      effect attributable to a lowering of plasma concentration. These elimination
      processes can be described using the clearance concept. METHODS: Data from four
      publications that investigated the time course of glomerular filtration rate and
      clearance of paracetamol, morphine and tramadol were reanalyzed. The effect of
      birth, based on postnatal age, was used in conjunction with a theory-based
      allometric size scaling and maturation based on postmenstrual age. RESULTS:
      Postnatal age had a short-term effect on the time course of clearance
      distinguishable from the well-known slower maturation based on postmenstrual age.
      While elimination might be relatively reduced by 15%-45% at birth, there is a
      rapid increase in elimination for 1-3 weeks after birth to be 15% greater than
      that predicted by postmenstrual age alone. CONCLUSION: Birth is associated with a
      small increase in clearance in addition to that described by postmenstrual age
      for common analgesic drugs cleared by glucuronide conjugation (morphine,
      paracetamol) or by the P450 cytochrome oxidase (tramadol) and renal systems.
      While the increase is of biological interest, it would not be expected to have
      any clinically relevant impact on renal function or drug dosing. The processes of
      maturation described by these models are potentially applicable to any drug
      elimination process.

PMID- 30303267
TI  - Osseous involvement in calcific tendinitis: unusual in the usual.
AB  - 62-year-old male, consulting for ongoing pain in the right shoulder, noticeable
      on performance of daily tasks. Physical examination demonstrates generalized pain
      with mobilization, more marked with external rotation, and limited abduction,
      with a mechanical block at 60 degrees. Oblique-Sagittal Short-TI inversion
      recovery (STIR) (figure 1) demonstrates a low signal intensity structure at the
      footprint of the infraspinatus (white arrow). This has an extra and an
      intraosseous component, resembling an hourglass. Adjacent to the intraosseous
      component, there is hyperintensity of the bone marrow, consistent with edema, and
      also a surrounding region of hyperintensity, representing edema, in the soft
      tissues. This article is protected by copyright. All rights reserved.

PMID- 30303268
TI  - Rheumatoid factor reactivity of expanded CD21-/low B cells in patients with
      Sjogren's syndrome: comment on the article by Glauzy et al.

PMID- 30303269
TI  - Circulating C1q/TNF-related protein isoform 15 is a marker for the presence of
      metabolic syndrome.
AB  - BACKGROUND: C1q/TNF-related protein isoform 15 (CTRP15) has been reported to be
      related to glucose and lipid metabolism, but the results are inconsistent.
      Metabolic syndrome (MetS) is a cluster of metabolic disorders. The aim of this
      study is to determine circulating CTRP15 levels in individuals with MetS and
      investigate the association among circulating CTRP15 and markers for MetS as well
      as insulin resistance. METHODS: A total of 341 individuals were recruited for
      this cross-sectional study. These subjects were screened for MetS. Serum CTRP15
      concentrations were measured by ELISA. RESULTS: Serum CTRP15 levels were
      significantly higher in MetS individuals relative to those of the healthy
      individuals. Circulating CTRP15 correlated positively with WHR, BMI, SBP, FAT %,
      2 h-BG, FIns, 2 h-Ins, TG, FFA, HbA1c, HOMA-IR, and AUCglucose , while negatively
      with HDL-C and ISI. Multiple linear regression showed that HOMA-IR and HDL-C are
      independently related factors influencing serum CTRP15 concentrations. In
      addition, binary logistic regression analysis showed that serum CTRP15
      concentrations were significantly related to MetS. When the mean concentrations
      of circulating CTRP15 in MetS subjects were stratified by the number of
      components of the MetS, circulating CTRP15 was found to increase progressively
      with increasing number of the MetS components. Finally, ROC curve analysis showed
      that the best cutoff values for circulating CTRP15 to predict MetS and insulin
      resistance were 63.6 and 64.0 MUg/L. CONCLUSIONS: Serum CTRP15 concentrations
      were associated with the key components of MetS and insulin resistance.

PMID- 30303271
TI  - Chlorophyllin supplementation modulates hyperglycemia-induced oxidative stress
      and apoptosis in liver of streptozotocin-administered mice.
AB  - Chlorophyllin is a water-soluble mixture of sodium-copper salts of chlorophyll
      with antioxidant and antimutagen properties. In this study, an attempt has been
      made to evaluate the effect of chlorophyllin on hyperglycemia-induced oxidative
      stress and apoptosis in liver of streptozotocin (STZ)-administered mice. In STZ
      induced diabetes, two causative factors for pancreatic beta-cell deaths are DNA
      alkylation and profound reactive oxygen species (ROS) generation. In this study,
      chlorophyllin treatment was found to be able to modulate oxidative stress and
      apoptosis in liver of diabetic mice. Diabetic mice exhibited a significant
      reduction of ROS, malondialdehyde (MDA), and protein carbonyl levels upon
      treatment with the chlorophyllin. However, antioxidant enzymes, such as copper
      zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), and
      catalase (CAT) showed enhanced activity as well as expression in chlorophyllin
      administered diabetic mice. The hepatoprotective effect of chlorophyllin was
      confirmed from the decreased activity of aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), and alkaline phosphatase (ALP). The histological
      and ultrastructural studies revealed the ability of chlorophyllin to restore
      morphological and cellular alterations as observed in STZ-induced diabetic mice.
      The effect of chlorophyllin on apoptosis showed the downregulation of cysteine
      dependent aspartate-specific protease (caspase) 3 and caspase 9, whereas
      upregulation of B-cell lymphoma-2 (Bcl-2) protein, and the terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay
      demonstrated a few apoptotic cells. In conclusion, it can be stated that
      chlorophyllin treatment can exert hepatoprotective effect via modulating
      hyperglycemia-induced oxidative stress and apoptosis in STZ-administered diabetic
      mice. (c) 2018 BioFactors, 44(5):418-430, 2018.

PMID- 30303270
TI  - Correlates of hair cortisol concentrations in disadvantaged young children.
AB  - Children from highly disadvantaged families tend to experience worse health,
      educational, and job outcomes than less disadvantaged peers. However, the
      mechanisms underlying these relationships remain to be explicated. In particular,
      few studies have investigated the relationships between the psychosocial
      influences that children are exposed to early in life and longer term cortisol
      output. This study aims to contribute to the literature by exploring how
      disadvantaged young children's experiences of family adversity, and parenting and
      family functioning, are related to their long-term cortisol levels. A sample of
      60 children (26 males, mean = 4.25 years, SD = 1.68) and their mothers (mean =
      34.18 years, SD = 7.11) from a low-income population took part in a single
      assessment. Mothers completed questionnaires on the family environment, parenting
      practices, and child behaviour. Children provided a hair sample for cortisol
      assay and anthropometric measures. A parsimonious multivariate regression model
      (including potential predictors identified by a selection algorithm) was used to
      investigate the correlates of hair cortisol concentration (HCC) in children.
      Higher levels of social exclusion, being male, and younger age were each
      associated with higher HCC. Maternal nurturing and emotion coaching were
      associated with lower HCC. Findings suggest that chronic stress may underlie
      relationships between adversity and its long-term effects and that HCC offers a
      promising method for examining chronic stress in children and evaluating
      interventions by which it can be ameliorated.

PMID- 30303272
TI  - Analysis of the technical efficiency of the forms of hospital management based on
      public-private collaboration of the Madrid Health Service, as compared with
      traditional management.
AB  - FUNDAMENTALS: The study aims to carry out a comparative analysis of the technical
      efficiency of hospital management based on public-private collaboration, as
      compared with traditional management. Specifically, we compare traditionally
      managed public hospitals, public hospitals managed by a private finance
      initiative (PFI), public hospitals managed through a public-private partnership
      (PPP), and hospitals managed through other forms of management, during the period
      2009 to 2014, in the hospitals dependent on the Madrid Health Service (SERMAS).
      METHODS: The study covers all publicly owned general hospitals under SERMAS,
      consisting of seven PFI hospitals, three PPP hospitals, 11 traditionally managed
      public hospitals (with the category of general hospital), and four hospitals
      managed through other forms of hospital management. The technical efficiency
      indices of the hospitals were calculated using the data envelopment analysis
      technique. Subsequently, a sensitivity analysis was performed by bootstrapping
      and variation of model variables to verify their impact on efficiency. Finally,
      an analysis of the evolution of efficiency in the analyzed period was carried out
      using the Malmquist Index. RESULTS: In all the analysis models carried out in the
      analyzed period, the hospitals managed based on public-private collaboration were
      more efficient than the hospitals under traditional management. CONCLUSIONS: The
      greater efficiency of hospitals managed based on public-private collaboration, as
      compared with traditional management, could be attributed to greater
      organizational and management flexibility.

PMID- 30303273
TI  - Special issue: Trans-Tasman Issue.

PMID- 30303274
TI  - Perceptions towards research and academia by Maori and Pacific preclinical
      medical students.

PMID- 30303275
TI  - Learning from history: How research evidence can inform policies to improve rural
      and remote medical workforce distribution.
AB  - OBJECTIVE: This article describes the rationale for, and development of, an
      evidence-based rural typology as the basis for an incentive scheme to improve
      medical workforce retention. This case study describes the key factors associated
      with ensuring that research evidence is translated into rural health policy and
      program implementation. DESIGN: Case study. SETTING: Rural and remote Australia.
      RESULTS: The development and implementation of the Modified Monash Model in
      Australia demonstrates some of the key facilitators of knowledge exchange. These
      include: sound evidence based on good empirical data and rigorous methodology;
      transparency to peers and stakeholders; the importance of long-term commitment to
      rural health research; the credibility of the researcher; multiple modes of
      communication of results; real world validation and amplification of results;
      patience and persistence underscored by the commitment of researchers to
      achieving more equitable outcomes for rural and remote doctors; serendipity in
      terms of timing; and a governmental culture that values evidence-based outcomes.
      CONCLUSION: The knowledge exchange process is neither easy nor simple and rarely
      rapid. It often requires the engagement of communities, professional
      associations, health care providers, researchers, policy-makers and funders.
      Implementation of evidence into rural health policies and programs benefits all
      parties through significant improvements in efficiency, effectiveness and equity.

PMID- 30303276
TI  - Alliances and evidence: Building the capacity and effectiveness of rural health
      advocacy in Australia.
AB  - This article describes two strategies that have strengthened the capacity and
      effectiveness of rural health advocacy in Australia over the past nearly three
      decades. The first is the development of the National Rural Health Alliance, an
      organisation that grew from strategic efforts to develop relationships between
      rural and remote health practitioners and organisations. The second is the
      development, organisation and use of data and evidence to highlight rural health
      needs. There has been important synergy between these two streams of activity,
      with research and evidence providing the tools and the National Rural Health
      Alliance providing the strategy and techniques to influence the rural and remote
      health care agenda.

PMID- 30303277
TI  - Kete pikau: A basket of knowledge - 'guidelines from back home'.
AB  - From the perspective of one rural New Zealand Maori community involved in a
      health service research study, this article describes 'Te Tomokanga' - an
      established local Maori model of engagement. This model served as an essential
      guide for researchers coming into the community and at the same time, enabled the
      community to take ownership of the research process. This may have applicability
      to research in rural Indigenous communities elsewhere.

PMID- 30303278
TI  - Point-of-care ultrasound in rural New Zealand: Safety, quality and impact on
      patient management.
AB  - OBJECTIVE: To evaluate the safety, quality and impact of point-of-care ultrasound
      on patient management when performed by rural generalist doctors. DESIGN: Cross
      sectional descriptive study. SETTING: Six rural small hospitals serving a range
      of communities in rural New Zealand. PARTICIPANTS: All generalist doctors
      practising ultrasound in the study hospitals. MAIN OUTCOME MEASURES: Technical
      quality, accuracy, impact on diagnostic certainty, patient disposition and
      overall patient care. RESULT: Participants correctly interpreted 90% of images
      and a similar percentage of point-of-care ultrasound findings when compared with
      the results of formal imaging or the final diagnosis. In total, 87% of scans
      contributed to the diagnostic process, changing the diagnostic probability. There
      was a 4% overall reduction in the number of patients needing hospital admission
      or transfer to an urban base hospital. The overall impact on patient care was
      positive for 71% of point-of-care ultrasound scans. Three percent of scans had
      the potential for patient harm. CONCLUSION: Rural generalists' practise a broad
      scope of point-of-care ultrasound that, when used as a part of the full clinical
      assessment, has a positive impact on patient care, improving diagnostic certainty
      and reducing the need for hospital admission and inter-hospital transfer. There
      are challenges in learning and maintaining the skills needed to practise a high
      standard of point-of-care ultrasound in this context. Further consideration needs
      to be given to the development safe scopes of practice, training, credentialing
      and quality assurance.

PMID- 30303280
TI  - Alliances and evidence: Building capacity and effectiveness of rural health
      advocacy in Australia: New Zealand commentary.

PMID- 30303279
TI  - Osteoporosis and low bone mineral density (osteopenia) in rural and remote
      Queensland.
AB  - OBJECTIVE: To report that prevalence rates of osteoporosis and osteopenia differ
      according to different levels of remoteness in Queensland, Australia. DESIGN:
      Retrospective analysis of bone mineral density scans undertaken between April
      2015 and April 2016. SETTING: Mobile laboratory housing a dual energy X-ray
      absorptiometry in rural and remote Queensland. PARTICIPANTS: Four-thousand-four
      hundred-and-twenty-seven referred individuals 70 years of age or older. MAIN
      OUTCOME MEASURES: Bone mineral density (g cm-2 ) at two sites was used to measure
      the level of bone health as per the World Health Organization criteria for
      osteoporosis. RESULTS: A slightly higher percentage of women was screened and the
      percentage screened in both men and women decreased as levels of remoteness
      increased. Women in outer regional areas had significantly higher odds of having
      osteopenia over normal bone mineral density, compared to women in an urban
      setting. CONCLUSION: As the level of remoteness increased, there was a decrease
      in the percentage of men and women being screened to determine their risk of
      osteoporosis. Furthermore, the current data suggest that women in more remote
      areas have significantly lower bone density, compared to an urban female
      population. Finally, men and women have similar levels of osteopenia across
      Queensland, Australia.

PMID- 30303281
TI  - Framework for examining the spatial equity and sustainability of general
      practitioner services.
AB  - OBJECTIVE: To propose a framework for examining both the spatial equity and
      sustainability of GP services. DESIGN: A conceptual discussion based on a
      systematic literature review of spatial equity definitions and methods. SETTING:
      Improving the spatial equity of health services is a key step in achieving health
      equity. Health systems should contribute to achieving health equity and maintain
      equitable services into the future. The GP services are a key component of
      primary health care, which often aims to promote health equity. Despite the
      importance of spatially equitable and sustainable GP services, a framework for
      analysis has not yet been established. MAIN OUTCOME MEASURE: Examples of how the
      proposed framework could be implemented are provided from the New Zealand health
      care context. RESULT: The framework entails three steps: (i) defining spatial
      equity and sustainability; (ii) estimating current and future distributions of
      health services and needs; and (iii) quantifying spatial equity and
      sustainability. In step (i), a needs-based distribution is the most common
      definition of spatial equity, while sustainability is the ability to provide
      ongoing equitable access. Step (ii) depends on current and future estimates of
      access and need within a well-defined geographical area. In step (iii), spatial
      equity and sustainability should be quantified through measures, such as the Gini
      coefficient. Current and future levels of spatial equity should then be compared
      to assess the sustainability of equitable GP services. CONCLUSION: This article
      outlines a novel conceptual framework for examining the spatial equitability and
      sustainability of GP services.

PMID- 30303282
TI  - Not counting.

PMID- 30303283
TI  - Research, education, advocacy: Keys to rural health success.

PMID- 30303284
TI  - Paramedicine in Australia and New Zealand: A comparative overview.
AB  - Paramedic services in Australia and New Zealand (Australasia) share many
      characteristics, with both offering versions of the Anglo-American system of
      emergency medical response. Their industry and professional bodies are
      transnational and as a result have similar industry standards and professional
      expectations. The major difference been the two countries is their sources of
      funding, with Australian paramedic services generally receiving more government
      funding than those in New Zealand. Both countries provide a range of services
      that use a mix of volunteer and professional staff and employ state-of-the-art
      communications and medical technology to provide high-level clinical services. In
      common with other higher income countries, they face the challenge of rising
      usage associated with ageing populations. Both countries are adapting to this
      through broadening their response models, from a focus on emergency medical
      response to the provision of a mobile health service that will see the emergence
      of more practitioners paramedic roles. These emerging models challenge the core
      missions of paramedic services, as well as the professional identity of
      paramedics. Despite these trends towards higher level and well-integrated
      paramedic services in Australia and New Zealand, communities and many other
      health professionals have limited knowledge or understanding of how paramedic
      services are organised, the characteristics of paramedics and allied staff and
      limited appreciation of their potential to make greater contributions to the
      health and well-being of communities. This article provides an introduction to
      how paramedics, as members of multidisciplinary teams, are well placed to
      contribute to improvements in health outcomes.

PMID- 30303286
TI  - Kete pikau: A basket of knowledge - 'guidelines from back home'.

PMID- 30303285
TI  - Improving the physical health of people living with mental illness in Australia
      and New Zealand.
AB  - People diagnosed with mental illness have relatively poor physical health and die
      earlier than their counterparts in the general population. People living with
      mental illness in rural Australia have three times the risk of premature death
      than the total population. This article reviews recent international, Australian
      and New Zealand research, identifies the increased risk of early death of people
      living with mental health issues in rural settings and looks at the need for
      policy and practice responses. The 'Equally Well' national initiatives are
      described in Australia and New Zealand, which seek to systematically address this
      inequity as a matter of priority. Finally, it argues for co-design and consumer
      participation in policy development, program implementation and research.
      Improved understanding of the perspectives and priorities of people with
      experience of mental illness is vital if change is to be fully realised.

PMID- 30303288
TI  - Rural health: An investment in regional development.

PMID- 30303287
TI  - Two decades of building capacity in rural health education, training and research
      in Australia: University Departments of Rural Health and Rural Clinical Schools.
AB  - This review article reports on the contribution of university Departments of
      Rural Health and Rural Clinical Schools to the development of rural health and
      the rural health workforce and is set at the Australian Government's university
      Departments of Rural Health and Rural Clinical Training and Support Programs. The
      main outcome measures include educational infrastructure, clinical academic
      workforce, student numbers, community engagement, research outputs, rural health
      and workforce outcomes. As a result, university Departments of Rural Health and
      Rural Clinical Schools have established a substantial geographical footprint
      covering most of the rural and remote populations and regions across Australia.
      They have a large distributed rural clinical academic workforce that exceeds
      1300. Medical student numbers on long-term placements have increased threefold
      from inception to 1200 annually. Allied health and nursing numbers doubled over
      10 years to 4000 in 2013 and are projected to double again by 2018. In 2013, they
      published 363 peer-reviewed papers - half of which specifically addressed rural
      and/or remote health issues. High levels of intention to practise rurally and
      uptake of rural and remote practice following exposure to rural training have
      been reported, especially for medicine. Thus, university Departments of Rural
      Health and Rural Clinical Schools constitute a national network of academic units
      that deliver academically enriched clinical education and training for medical,
      nursing and allied health students and fulfil an essential academic role for the
      health system in rural and remote Australia. Community engagement and
      accountability to region are hallmarks of the program. Early evidence of the
      uptake of rural and remote practice following exposure to rural training has set
      expectations for the Rural Health Multidisciplinary Training Program.

PMID- 30303289
TI  - Grasping the Ongaonga: When will New Zealand really integrate rural clinical
      education?
AB  - Compared to Australia, substantial rural-based clinical education in New Zealand
      started small and still has some way to go if it is to fulfil its potential in
      workforce retention and recruitment to under-served areas. The authors share some
      of their experiences in rural medical education and then speculate on how it
      could develop. They discuss the merits of a clinical school composed of a
      dispersed network of rural sites, which provide and coordinate rural health
      education.

PMID- 30303290
TI  - Crystallization-Induced Emission Enhancement of a Deep-Blue Luminescence Material
      with Tunable Mechano- and Thermochromism.
AB  - Organic luminescent materials with the ability to reversibly switch the
      luminescence when subjected to external stimuli have attracted considerable
      interest in recent years. However, the examples of luminescent materials that
      exhibit multiresponsive properties are rarely reported. In this work, a new
      stimuli-responsive dye P1 is designed and synthesized with two identical
      chromophores of naphthalimide, one at each side of an amidoamine-based spacer.
      This amide-rich molecule offers many possibilities for forming intra- and
      intermolecular hydrogen bond interactions. Particularly, P1 has an intrinsic
      property of cocrystallizing with methanol. Compared with the pristine P1 sample,
      the as-prepared two-component cocrystalline material displays an exceptive deep
      blue emission, which is extremely rare among naphthalimide-based molecules in the
      solid state. Furthermore, the target material exhibits an obvious mechanochromic
      fluorescent behavior and a large spectral shift under force stimuli. On the other
      hand, the cocrystalline material shows an unusual "turn off" thermochromic
      luminescence accompanied by solvent evaporation. Moreover, using external stimuli
      to reversibly manipulate fluorescent quantum yields is rarely reported to date.
      The results demonstrate the feasibility of a new design strategy for solid-state
      luminescence switching materials: the incorporation of solvents into organic
      compounds by cocrystallization to obtain a crystalline state luminescence system.

PMID- 30303291
TI  - Controlled Air-Etching Synthesis of Porous-Carbon Nanotube Aerogels with
      Ultrafast Charging at 1000 A g-1.
AB  - Supercapacitors are energy storage systems capable of fast charging and
      discharging, thus generating superior power density. Porous carbon with high
      surface area and tunable pore size represents a promising candidate to construct
      ultrafast supercapacitors; so far, most porous carbon-based electrodes can only
      be charged to a moderate current density (100-200 A g-1), also with significant
      capacitance loss at increasing rate. Here, it is shown that a 3D aerogel
      consisting of interconnected 1D porous-carbon nanotubes (PCNs) can serve as a
      freestanding supercapacitor electrode with excellent rate performance. As a
      result, the PCN aerogel electrodes achieve 1) ultrafast charging at current
      densities up to 1000 A g-1 (corresponding to a charge period of 16 ms), which is
      the highest value among other porous carbon-based supercapacitors, 2) superior
      cycling stability at high charging rates (88% capacitance retention after 105
      cycles at 1000 A g-1). Mechanism study reveals favorable kinetics including a
      centralized pore size distribution at 0.8 nm which is a dominant factor to allow
      high-rate charging, a low and linear IR drop, and a metallic feature of 1D PCNs
      by theoretical calculation. The results indicate that 1D PCNs with controlled
      porous structures have potential applications in ultrafast energy conversion and
      storage.

PMID- 30303292
TI  - Multifunctional Catalysts for H2 O2 -Resistant Hydrogen Fuel Cells.
AB  - The development of hydrogen fuel cells is greatly hindered by the unwanted
      generation of H2 O2 at the cathode. A non-Pt cathode catalyst is now shown to be
      capable of simultaneously reducing both O2 and H2 O2 , thus rendering H2 O2 a
      useful part of the feed stream. The applicability of this unique catalyst is
      demonstrated by employing it in a fuel cell running on H2 /CO and O2 /H2 O2 .

PMID- 30303293
TI  - Older people with HIV are an essential part of the continuum of HIV care.

PMID- 30303294
TI  - Alkyne-Tagged Analogue of Jaspine B: New Tool for Identifying Jaspine B Mode of
      Action.
AB  - The first biologically relevant clickable probe related to the antitumor marine
      lipid jaspine B is reported. The concise synthetic route to both enantiomers
      relied on the supercritical fluid chromatography (SFC) enantiomeric resolution of
      racemic materials. The eutomeric dextrogyre derivative represents the first
      jaspine B analogue with enhanced cytotoxicity with IC50 down to 30 nm. These
      enantiomeric probes revealed a chiralitydependent cytoplasmic imaging of U2OS
      cancer cells by in situ click labeling.

PMID- 30303295
TI  - Spectroscopic Evidence for an Attractive Cation-Cation Interaction in Hydroxy
      Functionalized Ionic Liquids: A Hydrogen-Bonded Chain-like Trimer.
AB  - We address the formation of hydrogen bonded domains among the cationic
      constituents of the ionic liquid (IL) 1-(3-hydroxypropyl)pyridinium
      tetrafluoroborate [HPPy][BF4 ] by means of cryogenic ion vibrational
      predissociation spectroscopy of cold (ca. 35 K) gas-phase cluster ions and
      quantum chemistry. Specifically, analysis of the OH stretching bands reveals a
      chain-like OH???OH???OH???BF4 - binding motif involving the three cations in the
      cationic quinary cluster ion (HPPy+ )3 (BF4 - )2 . Calculations show that this
      cooperative H-bond attraction compensates for the repulsive Coulomb forces and
      results in stable complexes that successfully compete with those in which the OH
      groups are predominantly attached to the counter anions. Our combined
      experimental and theoretical approach provides insight into the cooperative
      effects that lead to the formation of hydrogen bonded domains involving the
      cationic constituents of ILs.

PMID- 30303296
TI  - The specificity of monoclonal anti citrulline protein antibodies - reply to Dr
      Holmdahl's letter.
AB  - Rikard Holmdahl has commented on our recently published paper on specificity and
      function of human monoclonal antibodies (mAbs) from synovial plasma cells that
      react with citrullinated proteins and peptides (1). He also comments on our
      previous study from 2013 (2) that was based on mAbs generated from synovial B
      cells. Dr Holmdahl's letter provides us with an opportunity to discuss and
      clarify some methodological issues concerning RA monoclonal autoantibody
      expression, specificity, and functionality. In our eyes, cloning and
      characterization of human monoclonal autoantibodies from patients represents an
      important approach to the understanding of origins and functions of
      autoantibodies in the pathogenesis of immune-mediated diseases. In fact, the RA
      field has been especially active on making use of mAbs derived from the
      immunoglobulin sequences from patient-derived B cells and plasma cells. This
      article is protected by copyright. All rights reserved.

PMID- 30303297
TI  - Exploring biogeographic patterns of bacterioplankton communities across global
      estuaries.
AB  - Estuaries provide an ideal niche to study structure and function of
      bacterioplankton communities owing to the presence of a multitude of
      environmental stressors. Bacterioplankton community structures from nine global
      estuaries were compared to understand their broad-scale biogeographic patterns.
      Bacterioplankton community structure from four estuaries of Sundarbans, namely
      Mooriganga, Thakuran, Matla, and Harinbhanga, was elucidated using Illumina
      sequencing. Bacterioplankton communities from these estuaries were compared
      against available bacterioplankton sequence data from Columbia, Delaware,
      Jiulong, Pearl, and Hangzhou estuaries. All nine estuaries were dominated by
      Proteobacteria. Other abundant phyla included Bacteroidetes, Firmicutes,
      Acidobacteria, Actinobacteria, Cyanobacteria, Planctomycetes, and
      Verrucomicrobia. The abundant bacterial phyla showed a ubiquitous presence across
      the estuaries. At class level, the overwhelming abundance of Gammaproteobacteria
      in the estuaries of Sundarbans and Columbia estuary clearly stood out amidst high
      abundance of Alphaproteobacteria observed in the other estuaries. Abundant
      bacterial families including Rhodobacteriaceae, Shingomonadaceae,
      Acidobacteriaceae, Vibrionaceae, and Xanthomondaceae also showed ubiquitous
      presence in the studied estuaries. However, rare taxa including Chloroflexi,
      Tenericutes, Nitrospirae, and Deinococcus-Thermus showed clear site-specific
      distribution patterns. Such distribution patterns were also reinstated by nMDS
      ordination plots. Such clustering patterns could hint toward the potential role
      of environmental parameters and substrate specificity which could result in
      distinct bacterioplankton communities at specific sites. The ubiquitous presence
      of abundant bacterioplankton groups along with their strong correlation with
      surface water temperature and dissolved nutrient concentrations indicates the
      role of such environmental parameters in shaping bacterioplankton community
      structure in estuaries. Overall, studies on biogeographic patters of
      bacterioplankton communities can provide interesting insights into ecosystem
      functioning and health of global estuaries.

PMID- 30303298
TI  - Effects of exendin-4 on colonic motility in rats and its underlying mechanism.
AB  - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists modulate
      gastrointestinal motility; however, the effects of GLP-1R agonists on colonic
      motility are still controversial, and the molecular mechanism is unclear. Exendin
      4 shares 53% homology with GLP-1 and is a full agonist of GLP-1R. In this study,
      our aims were to explore the role and mechanism of exendin-4 in isolated rat
      colonic tissues and cells. METHODS: An organ bath system was used to examine the
      spontaneous contractions of smooth muscle strips. The whole-cell patch-clamp
      technique was used to investigate the currents of L-type voltage-dependent
      calcium channels and large conductance Ca2+ -activated K+ (BKCa ) channels in
      smooth muscle cells. KEY RESULTS: Exendin-4 decreased both the amplitude and
      frequency of spontaneous contractions of smooth muscle strips in a concentration
      dependent manner. The inhibitory effect was completely blocked by exendin-4(9
      39), a GLP-1R antagonist. Moreover, this effect was partially abolished by
      tetrodotoxin (TTX), a blocker of neuronal voltage-dependent Na+ channels, Nomega
      Nitro-l-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor, apamin, an
      inhibitor of small-conductance Ca2+ -activated K+ (SK) channels. Whole-cell patch
      clamp recordings revealed that exendin-4 inhibited the peak current of L-type
      calcium channels in colonic smooth muscle cells, but did not change the shape of
      the current-voltage (I-V) curves. The steady-state activation and steady-state
      inactivation of L-type calcium channels were not affected. Likewise, BKCa
      currents were significantly inhibited by exendin-4. CONCLUSIONS: Exendin-4
      indirectly inhibits colonic muscle activity via a nitrergic and a purinergic
      neural pathway through NO and ATP release and inhibits L-type voltage-dependent
      calcium channels and BKCa channels in smooth muscle cells.

PMID- 30303299
TI  - Employees' and line managers' active involvement in participatory organizational
      interventions: Examining direct, reversed, and reciprocal effects on well-being.
AB  - This study examined how employee participation and perceptions of line managers'
      support during a participatory organizational intervention were related to well
      being over time. Although previous studies suggest that employees' and managers'
      active involvement in participatory organizational interventions may be related
      to well-being, little is known about the temporal aspects, such as at which time
      during the intervention these factors matter, or possible reciprocal effects.
      Building on conservation of resources theory, we tested hypotheses concerning
      direct, reversed, and reciprocal relationships between employee participation and
      perceptions of line manager support in relation to well-being. We used a four
      wave panel design consisting of 159 hospital workers. Cross-lagged analyses
      showed that perceived line managers' support in the initiation and active phase
      was related to participation in the active phase. Participation in the initiation
      and active phase was related to well-being in the active and sustained phase,
      respectively. Results also revealed that participation in the initiation phase
      was related to perceived line managers' support in the active phase, which in
      turn predicted participation in the active phase, which translated into job
      satisfaction in the sustained phase supporting reversed and reciprocal effects in
      the form of resource caravans. Theoretical implications for research and practice
      are discussed.

PMID- 30303300
TI  - The specificity of monoclonal anti-citrulline protein antibodies.
AB  - I read with great interest the article by Steen et al demonstrating that human
      plasma cell-derived monoclonal antibodies to post-translationally modified
      proteins recognize amino acid motifs rather than specific proteins (1). However,
      I believe some potentially misleading conclusions are drawn. In their paper, they
      report the isolation of IgG-secreting synovial plasma cells from one presumably
      high ACPA responder RA patient, followed by generation of the corresponding
      recombinant antibodies for evaluating their specificities and functions. This
      article is protected by copyright. All rights reserved.

PMID- 30303301
TI  - Experience with gluteal V-Y fasciocutaneous advancement flaps in vulvar
      reconstruction after oncological resection and a modification to the marking:
      Playing with tension lines.
AB  - Many post-vulvectomy vulvar reconstruction solutions, using local fasciocutaneous
      flaps where possible, have been proposed. We report the use of V-Y advancement
      flaps from the gluteal fold in medium to large vulvar reconstructions and a
      simple modification we made to the technique in order to minimise wound-related
      complications. Between 2006 and 2016, 30 vulvar reconstructions were performed
      via a total of 59 flaps, 24 of which were raised using the proposed modification
      to the plasty design. Short- and long-term (24 months) follow-up data were
      analysed, postoperative flap sensitivity was tested, and any arising
      complications were recorded. The mean age of patients treated was 75.3 years (51
      92 years). The mean monolateral defect dimensions were 7.5 * 4.7 * 2.8 cm. Minor
      complications were recorded in 23% of patients (14% of flaps). One case of ostial
      stenosis occurred. Micturition and ambulation recovery was rapid, and flap
      sensitivity was fully restored 24 months after reconstruction. Scars were well
      hidden by natural soft tissue folds. The outcomes in this case series confirm
      that the gluteal V-Y advancement fasciocutaneous flap is a useful and simple
      technique for reconstructing even large vulvar defects. It has a low functional
      and aesthetic impact and enables rapid return to autonomy. Moreover, the simple
      modification to the V-Y flap proposed, designed to reduce tension at the apical
      part of the wound, appears to reduce the complication rate.

PMID- 30303302
TI  - Psoriasis: identifying trends through search engines.

PMID- 30303303
TI  - New attempts to improve in vitro diagnosis of contact allergy are still far from
      regular clinical practice.

PMID- 30303304
TI  - Assessment of serious infections in pemphigus and pemphigoid by a national
      registry.

PMID- 30303305
TI  - Pioneers in dermatology and venereology: an interview with Prof. Helmut Kerl.

PMID- 30303306
TI  - Commentary to "Mogamulizumab-induced photosensitivity in patients with mycosis
      fungoides and other T-cell neoplasms" by Y. Masuda et al.

PMID- 30303307
TI  - Hidradenitis suppurativa in Korea.

PMID- 30303308
TI  - Does rTMS reduce depressive symptoms in young people who have not responded to
      antidepressants?
AB  - AIM: Depression is common in young people, and there is a need for safe,
      effective treatments. This study examined the efficacy of repetitive transcranial
      magnetic stimulation in a sample of young people aged 17 to 25 years. METHODS:
      This retrospective study included 15 people aged 17 to 25 years referred by their
      private psychiatrists affiliated with Ramsay Health Care, South Australia Mental
      Health Services. All patients met Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition criteria for treatment-resistant Major Depressive
      Disorder. Eleven patients received right unilateral treatment and four patients
      received bilateral treatment. Patients were assessed at baseline and after
      treatment. RESULTS: There was a significant improvement on the Hamilton Rating
      Scale for Depression (t(14) = 4.71, P < 0.0001); Montgomery-Asperg Depression
      Rating Scale (t(14) = 3.96, P < 0.01) and the Zung Self-Rating Depression Scale
      (t(14) = 4.13, P < 0.01). There was no difference in response by gender or age.
      The response rates in these young people did not differ significantly from those
      of adults aged 25 to 82 years. CONCLUSION: This open label, naturalistic study
      suggests that repetitive transcranial magnetic stimulation is an effective
      treatment in young adults who have treatment-resistant depression. Randomized
      sham-controlled studies are needed to further investigate the efficacy of this
      treatment in this age group.

PMID- 30303309
TI  - Divergent Dynamic Kinetic Resolution of a Racemic Mixture of Four Stereoisomers
      via N-Heterocyclic Carbene Organocatalysis.
AB  - Racemic mixtures of four stereoisomers are easily formed via many fundamental
      organic transformations, but the direct utilities of these mixtures have been
      less studied and remain large challenges to date. In this work, we introduce a
      new method, i.e., divergent dynamic kinetic resolution, to achieve the separation
      of racemic mixtures of four stereoisomers. The hypothesis was proved by using a N
      heterocyclic carbene-catalyzed benzoin reaction, which afforded two separable
      diastereomeric products bearing three consecutive stereocenters with good to
      excellent enantioselectivties. We believe that this resolution protocol will find
      applications in more transformations.

PMID- 30303310
TI  - An inexpensive method of negative pressure wound therapy for extremities.
AB  - Negative pressure wound therapy (NPWT) is an established method for the faster
      wound healing of chronic non-healing wounds. It is also used for laparostomy
      wounds and healing of split skin grafts. The commercially available machine and
      the consumables for NPWT are very expensive and economically not feasible in
      developing and underdeveloped countries. So, we devised a NPWT system for wounds
      of the extremity using inexpensive, readily available materials in any hospital.
      The materials used are sterile glove, autoclaved sponge, Foley catheter, and a
      wall suction unit. The sponge was placed over the wound, and a sterile glove was
      pulled over it. A Foley catheter was placed over the sponge and taken out through
      one of the fingers of the glove. Adhesive plaster was used to air-seal the glove.
      The Foley catheter was fixed with silk ties and connected to wall suction.
      Granulation and wound healing was faster in this system. This system was safe and
      inexpensive for the treatment of wounds of the extremity.

PMID- 30303311
TI  - The impact of sitagliptin, inhibitor of dipeptidyl peptidase-4 (DPP-4), on the
      ADMA-DDAH-NO pathway in ischemic and reperfused rat livers.
AB  - BACKGROUND: A correlation between the level of asymmetric dimethylarginine (ADMA)
      - the inhibitor of the nitric oxide (NO) synthesis - and the liver function and
      survival after a liver transplantation has been reported. OBJECTIVES: The aim of
      this study was to evaluate the effect of sitagliptin -the inhibitor of dipeptidyl
      peptidase-4 (DPP-4) - on the NO-ADMA-dimethylarginine dimethylaminohydrolase
      (DDAH) pathway in rat livers subjected to ischemia/reperfusion (IR). MATERIAL AND
      METHODS: The rats received sitagliptin (5 mg/kg, per os - p.o.) (groups: S -
      livers not subjected to IR procedure, and SIR - livers subjected to IR procedure)
      or a saline solution (groups: C - livers not subjected to IR procedure, and CIR -
      livers subjected to IR procedure) for 14 days; following this, livers in the SIR
      and CIR groups were subjected to ischemia (60 min) and reperfusion (24 h).
      Aminotransferases were measured before the surgery; additionally, the arginine
      (ARG), ADMA and symmetric dimethylarginine (SDMA) levels were estimated just
      before ischemia and during reperfusion (at 0.5, 4 and 24 h). After IR,
      citrulline, the DDAH activity, mRNA for type 1 DDAH (DDAH1), and arginine
      methyltransferase type 1 (PRMT1) were determined. RESULTS: The increase in the
      initial level of ARG/ADMA0 (A/A) ratio in group S compared to group C verged on
      statistical significance. At 0.5 and 4 h of reperfusion, the highest
      concentration of ADMA was found in group CIR. At those time points, the ARG level
      and the A/A ratio were decreased in groups CIR and SIR as compared to groups C
      and S, respectively. The alanine transaminase (ALT) activity was lower in the
      sitagliptin-treated group than in the non-treated one. The DDAH and citrulline
      levels were reduced in group CIR as compared to group C, but were greater in
      group SIR as compared to group S. The PRMT1 mRNA expression was higher in groups
      CIR and SIR, compared to groups C and S, respectively. CONCLUSIONS: The increased
      A/A ratio suggests a protective effect of sitagliptin on livers not subjected to
      IR. Changes in the DDAH activity and the PRMT1 mRNA expression also imply the
      protective activity of sitagliptin during IR.

PMID- 30303312
TI  - Effects of puerarin on spatial learning and memory function in mice with acute
      alcohol consumption: An evaluation based upon firing rate and oxygen saturation
      analysis.
AB  - BACKGROUND: Ethanol is associated with various medical comorbidities affecting
      the brain and central nervous system. OBJECTIVES: The use of puerarin in treating
      alcohol-induced memory disorders is systematically evaluated in this study based
      upon an analysis of the firing rate and oxygen saturation (SO2). MATERIAL AND
      METHODS: A multi-channel data acquisition system and near-infrared spectroscopy
      (NIRS) were combined to obtain the electroneurophysiological signals and SO2 in
      the hippocampus of mice from the Institute of Cancer Research (ICR) after ethanol
      injection. A T-maze test was performed to study the alteration of spatial memory
      function. Ethanol was administered intraperitoneally (i.p.) in 2 dosages (1.5
      g/kg and 0.5 g/kg). To investigate the effects of puerarin against acute ethanol
      induced memory impairment, the same parameters corresponding to
      electroneurophysiological signals, SO2 and behavior performance in mice were also
      recorded upon the supplementation of puerarin in 2 dosages (25 mg/kg and 50
      mg/kg). RESULTS: An inhibited firing rate and decreased SO2 were found in mice
      treated with an ethanol dose of 1.5 g/kg, which resulted in a low correct choice
      rate in the T-maze test, while an opposite trend appeared in mice which had been
      administered a moderate ethanol dose (0.5 g/kg). The trend of SO2 was positively
      correlated with that of the firing rate. A decreased firing rate and SO2 were
      accompanied by a decrease in the correct choice rate. With the supplementation of
      puerarin, a significant increase in the mean firing rate and SO2, as well as an
      improved correct choice rate, can be found in mice injected with excessive
      ethanol. CONCLUSIONS: The electroneurophysiological signals and NIRS were
      combined for the first time to prove that an excessive intake of ethanol can
      inhibit the spatial learning and memory function of mice. The supplementation of
      puerarin can suppress these adverse effects induced by ethanol at a high dosage,
      as evidenced by the increased firing rate and SO2.

PMID- 30303313
TI  - Mental Health Treatment in Rural Adolescent Mothers.

PMID- 30303316
TI  - Developing Interprofessional Education: A Nursing Perspective.

PMID- 30303318
TI  - Nursing and the LGBT Community in Kentucky.

PMID- 30303319
TI  - Unhealthy Children Equals an Unhealthy Commonwealth: The Need for School Nurses.
AB  - There is power in numbers and nurses are an influential group. Supporters cannot
      continue to wait on solutions that have not come. Nurses are powerful change
      agents and it is time to push for change! This change should be a nurse in every
      school in Kentucky for the health, safety and education of children.

PMID- 30303320
TI  - Dangerous Waters: An Exploration of Bathing Procedures Used in Kentucky's Acute
      and Long Term Care Facilities.

PMID- 30303321
TI  - Nursing Coalition Praises Commission on Care Recommendations to Improve Veterans'
      Healthcare.

PMID- 30303322
TI  - ?

PMID- 30303323
TI  - [Meniere's disease, endolymphatic hydrops and MRI].
AB  - Meniere's disease is characterized by episodic vertigo associated with
      fluctuating hearing loss, tinnitus and fullness of the ear on the affected side.
      Endolymphatic space enlargement - or endolymphatic hydrops (EH) - is a
      histological hallmark of the disease that does not explain all its clinical
      manifestations. Magnetic resonance imaging improvements now allow in vivo
      visualization of inner ear liquid spaces and appreciation of potential EH. This
      article discusses these advances and their potential diagnostic implications in
      the context of Meniere's disease and more generally in cochleovestibular
      disorders.

PMID- 30303324
TI  - [Spontaneous involution of Vestibular Schwannomas].
AB  - The majority of vestibular schwannomas have a stable evolution or a progression
      of size. Some publications report cases of spontaneous involution. We report here
      the clinical and radiological characteristics of this type of tumor observed in
      14 patients showing a spontaneous tumor involution of their vestibular
      schwannoma. The results showed an incidence of 8 % with an average tumor
      regression of 50 %. Functionally, a hearing loss was found in all patients,
      without correlation with the duration of the observational follow-up. There are
      spontaneously involutive vestibular schwannomas, but tumor regression does not
      prevent the deterioration of hearing. Patients should be considered as a subset
      of those receiving observational management.

PMID- 30303325
TI  - [A crazy patient or an additional weird experience vestibular in origin ?]
AB  - We present a patient suffering from persistence of images after cessation of the
      visual stimulus, a phenomenon called palinopsia. As none of classical causes
      existed in this patient, we hypothethized that the phenomenon is related to the
      particular dysfunction of his right inner ear associating a canalar deficit with
      a preserved otolithic function. In such a situation, the vestibular inputs are
      slower than normal. Therefore, palinopsia could result from an abnormal temporal
      integration of visual and vestibular informations.

PMID- 30303326
TI  - [Psychophysical olfactory testing : what's new ?]
AB  - Olfactory disorders are common and may lead to severe consequences on quality of
      life. Medical management including treatment options can be proposed to the
      patients. For this reason, a correct diagnosis is important. Olfactory testing is
      one of the cornerstones for the diagnosis of smell impairment which helps to
      quantify the deficit. Despite good and widespread psychophysical olfactory tests,
      there are still many challenges in testing olfaction. Most of the current
      available test may not fully account for some cultural and genetic biases.
      Therefore it is difficult to develop olfactory tests and standardize them across
      different populations. In this paper we discuss an alternative method based on "
      white smells " which may help to overcome these issues.

PMID- 30303327
TI  - [Sleep apnea : diagnostic and therapeutic modalities in case of failure of the
      CPAP].
AB  - Obstructive sleep apnea (OSA) is a sleep disorder that affects 49 % of men and
      23% of women over 40 years old. CPAP is currently the treatment of choice for
      severe OSAS, but there are mild to moderate cases of OSAS with poor compliance or
      intolerance to CPAP, for which alternative treatments should be considered. In
      this article, we present a tool for evaluation of the upper airways, the DISE
      (Drug-induced sleep endoscopy), the OAM (mandibular advancement device), the
      bimaxillary advancement osteotomy, the hypoglossal nerve stimulation and the
      positional treatment.

PMID- 30303328
TI  - [Salivary management in amyotrophic lateral sclerosis].
AB  - 80 % of patients suffering from amyotrophic lateral sclerosis present bulbar
      involvement and 50 % have salivary symptoms, which are often poorly managed. They
      present either with drooling or thick secretions. This elevates the risk of
      bronchoaspiration leading to pneumonia, second cause of death in this population.
      It is hence paramount to treat, while enhancing the patient's quality of life.
      The first line of treatment is a salivary drying agent such as an atropine-based
      medication. These treatments have a low adverse effect rate, are reversible and
      easy to dose. Management of thick secretions is possible with mucolytics. Taking
      into account the severity of the bulbar involvement, the second line of
      treatment, once controversial, is salivary gland injections of botulinium toxin.

PMID- 30303330
TI  - ?

PMID- 30303329
TI  - [Giving a future to transgender youth... What do we currently know of their
      needs, what are the best practices ?]
AB  - Since 2011, a significant amount of evidence has been published on transgender
      children and adolescents, highlighting their needs and the best health and social
      practices. They are more at risk of suicide, discrimination, depression. Today,
      we better understand that the main causal factor linked with negative experiences
      is to be found in direct and indirect discriminations, subsequently causing
      personal and relational difficulties. When transgender youth are fully accepted
      and supported in their desired gender, they do not significantly differ from
      other youth. We need to build informed and respectful practices. Three kind of
      interventions are now urgently needed in Switzerland: access to hormonal
      management of puberty (medical), family centered interventions (psychosocial),
      and prevention of bullying in schools (sociopolitical).

PMID- 30303331
TI  - ?

PMID- 30303333
TI  - ?

PMID- 30303332
TI  - ?

PMID- 30303334
TI  - ?

PMID- 30303335
TI  - ?

PMID- 30303336
TI  - [PERSONALIZED MEDICINE IN INTERNAL MEDICINE].
AB  - Personalized medicine - a new direction in medicine, which is based on the study
      of various biomarkers and the use of new methods of molecular analysis (primarily
      evaluating the activity of isoenzymes of cytochrome P450), allowing
      individualized approach to the selection of both the drugs and the selection of
      the dosing regimen for the purpose of maximize the effectiveness and safety of
      pharmacotherapy. This personalized medicine is to change the development and use
      of preventive and curative interventions. Genetic polymorphism isozymes of
      cytochrome P450 may determine the individual activity of a particular isozyme,
      and thus, to predict the clinical effectiveness, and in some cases, the risk of
      adverse reactions. The article is an example of the use of information on the
      activity of cytochrome P450 in clinical practice in matters of diagnosis,
      treatment and prevention of diseases. The scheme of the five best-known activity
      of isoenzymes of cytochrome P450 is shown.

PMID- 30303337
TI  - [ANEMIA OF CHRONIC DISEASES AS A SYSTEMIC MANIFESTATION OF CHRONIC PULMONARY
      OBSTRUCTIVE DISEASE].
AB  - Anemia of chronic disease (ACD) is one of the most frequent forms of anemia is
      often observed in patients with infections, cancer and chronic inflammatory or
      autoimmune diseases. The underlying mechanisms are complex and include
      dysregulation of iron homeostasis and erythropoietin production, impaired
      proliferation of erythroid progenitor cells and reduced life span of red blood
      cells. Moreover, ACD is often superimposed by malnutrition, bleeding and renal
      failure. ACD is mediated through inflammatory cytokines and characterized by low
      serum iron (hypoferremia) and often increased reticuloendothelial stores of iron.
      ACD is usually normocytic, normochromic anemia, but it can become microcytic and
      hypochromic as the disease progresses. Hepcidin, the main regulator of iron
      homeostasis and its synthesis, is inhibited by iron deficiency and stimulated by
      inflammation. In many patients the disease is associated with several
      extrapulmonary manifestations regarded as the expression of the systemic
      inflammatory state of chronic obstructive pulmonary disease (COPD). Recent
      studies showed that anemia in patients with COPD is more frequent than expected,
      with its prevalence ranging from 8 to 33%. Systemic inflammation may be an
      important pathogenic factor, but anemia in COPD can also be the result of a
      number of factors, such as the treatment with certain drugs (angiotensin
      converting enzyme inhibitors or theophylline), endocrine disorders, acute
      exacerbations and oxygen therapy. Anemia in COPD patients is strongly associated
      with increased functional dyspnea, decreased exercise capacity and is an
      independent predictor of mortality. Treatment options to correct anemia used in
      other chronic diseases, such as congestive heart failure, cancer or chronic
      kidney disease have not been explored in COPD (i.e. erythropoietic agents, iron
      supplements or combined therapy). It is not known whether treating the underlying
      inflammation could improve hematological characteristics. It is important to
      develop basic diagnostic modalities for this group of patients and formulate
      methods of anemia correction.

PMID- 30303338
TI  - [DIAGNOSTIC SIGNIFICANCE OF PLASMA TROPONIN AND CARDIOMYOCYTE FATTY ACID-BINDING
      PROTEIN LEVELS IN ACUTE CORONARY SYNDROME].
AB  - Blood serum content of fatty acid-binding (FABP) protein increases within 2-3 h
      after the onset of acute coronary syndrome and myocardial infarction (MI) and
      reaches the maximum 8.5 h after the initiation of cardiomyocyte death. FABP
      content considerably decreases by the end of at 24-h period due to excretion with
      urine, remaining elevated for subsequent 24 h. High clinical sensitivity and
      relatively high organ specificity are typical of FABP for 12 h after ACS. Within
      the early period of MI clinical specificity of FABP prevails over troponin in
      terms of concentration. Troponins display higher clinical sensitivity and
      diagnostic specificity during a 12-h period after ACS, prevailing for several
      days after MI. Simultaneous measuring of FABP and troponins (Tr) within the first
      12 h increases the sensitivity of biochemical diagnostics by 30%. At later
      periods, simultaneous determination of FABP and Tr becomes unnecessary: FABP is
      excreted with urine and Tr level acquires predominant diagnostic significance. No
      relationship has been revealed between blood content of FABP and reperfusion
      according to electrocardiography data, probably due to rare measurements of this
      highly dynamic parameter. FABP test cannot be used in patients with circulatory
      disorders since its results are not adequate. The best option for differential
      diagnostics of ACS within the first 24 h would be a combined express
      immunochromatographic test which allows to measure blood FABP and Tr levels
      pending objective evaluation.

PMID- 30303339
TI  - [DESIALATED LOW DENSITY LIPOPROTEINS IN HUMAN BLOOD].
AB  - The present article is a review of literature on circulating low-density
      lipoproteins (LDLP) which can induce accumulation of lipids (mainly,
      cholesterol), in a SMA(+) cell culture of normal human aortic intima. An attempt
      was undertaken to resolve the paradox of the absence of both native LDLP
      influence on intracellular lipid accumulation and modifications of in vitro
      obtained LDLP in the blood-vascular system. It was showed that atherogenic LDLPs
      are characterized by a number of changes in carbon, protein and lipid components
      which can be regarded as multiple modifications of LDLP taking place in human
      blood plasma. Multiply modified circulating LDLP possess of capacity to interact
      with various cell membrane receptors differing from B and E receptor, and with
      proteoglycans. Marked absorption of desiliated LDLPs by the cells simultaneous
      with a decrease in the degradation of apolipoproteins and cholesterol esters as
      well as induction of peresterification of free cholesterol leads to intracellular
      accumulation of esterified cholesterol. Formation of large LDLP-containing
      complexes especially circulating low-density lipoproteins can stimulate
      accumulation of lipids by smooth muscle cells of intima. Desiliated LDLPs
      stimulated cell proliferation and connective tissue matrix synthesis despite
      cholesterol ester accumulation. In conclusion, the authors of this article found
      and characterized natural multiply modified LDLPs that can be responsible for the
      symptoms of atherosclerosis at the cellular level.

PMID- 30303340
TI  - Challenges and future developments in liver transplantation.
AB  - Liver transplantation (LT) has become the treatment of choice for a wide range of
      liver diseases in both adult and pediatric patients. Until recently, the largest
      proportion of LT in adults, were performed in patients with hepatitis C (HCV)
      related cirrhosis. The recent availability of safe and effective direct antiviral
      agents to cure HCV infection in almost all patients whatever the HCV genotype and
      severity of liver disease, will reduce the need for LT in this category of
      recipients. Thus, it is presumed that in the next 1 to 2 decades HCV related
      liver disease will diminish substantially, whereas non-alcoholic steato-hepatitis
      (NASH) will correspondingly escalate as an indication for LT. The greatest
      challenges facing LT remain the limited supply of donor organs, and the need for
      chronic immunosuppression, which represent the true obstacles to the greater
      application and durable success of the LT procedure. This review aims to
      highlight, in different sections, the main open issues and future developments in
      LT. These will be focused to explore current and future strategies to maximize
      the use of limited organs, to offer an update on potential new approaches to
      immunosuppression and to imagine new indications for LT when the number of
      patients awaiting transplants for HCV related liver disease is reduced.

PMID- 30303341
TI  - [TRENDS IN DEVELOPMENT OF GI-SAFE ANTI-INFLAMMATORY DRUGS].
AB  - Despite the introduction of anti-inflammatory drugs that selectively inhibit
      cyclo-oxygenase-2 (COX-2), and potent inhibitors of gastric acid secretion, the
      gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs
      (NSAIDs) remain a significant clinical problem. Combined use of antisecretory
      drugs and COX-2 inhibitors is helpful to limit the damage in the proximal
      gastrointestinal tract (stomach and duodenum), but it increases the risk of
      injury of small intestine and colon. It was proven that proton pump inhibitors
      and H2 receptor antagonists significantly worsen NSAID-induced small intestinal
      damage and microbiota balance. Nowadays, there is no proven effective
      preventative or curative treatment for NSAID-induced enteropathy. The new
      strategy of gastrointestinal protection is based on the discovery of endogenous
      cytoprotective molecules such as hydrogen sulfide (H2S). H2S is a gaseous
      mediator that produces strong cytoprotective and antioxidant effect on the
      gastrointestinal tract. The role of H2S in promoting mucosal integrity, healing
      of tissue injury and resolution of inflammation has been well documented. In
      addition, H2S stimulates productions of other cytoprotective molecules including
      prostaglandins, carbon monoxide and nitric oxide. Nowadays, the new generation of
      H2S-releasing non-steroidal anti-inflammatory drugs is developed and tested in
      clinical trials. H2S-NSAIDs possess enhanced anti-inflammatory activity and high
      gastrointestinal safety.

PMID- 30303342
TI  - [CHARACTERISTICS OF BONE MINERAL DENSITY IN ELDERLY PATIENTS WITH DIABETES
      MELLITUS].
AB  - Diabetes mellitus is a most important medical and social problem in Russia.
      Osteoarthropathy, osteopenia and osteoporosis are chronic complications of
      diabetes. There is no consensus on the pathogenetic mechanisms of development of
      changes of the bone tissue in this pathology. The present literature review
      outlines the problem.

PMID- 30303343
TI  - Transcatheter aortic valve implantation without prior balloon valvuloplasty is
      associated with less pronounced markers of myocardial injury.
AB  - BACKGROUND: Aortic valve stenosis is the most common valvulopathy in developed
      countries. Transcatheter aortic valve implantation (TAVI) is a therapeutic
      alternative in symptomatic patients at high or prohibitive perioperative risk.
      Predilatation by balloon aortic valvuloplasty (BAV) under rapid ventricular
      pacing (RVP) has been a routine part of TAVI. However, both RVP and BAV carry
      substantial risks and an increasing number of interventional centers are
      performing TAVI without predilatation (direct TAVI). A transient decrease of left
      ventricular function and elevated markers of myocardial injury after TAVI with
      predilatation were observed in previous studies. In this study, we investigated
      whether direct TAVI was associated with a similar increase in cardiac biomarkers
      and decrease in ejection fraction in a cohort of our patients. METHODS:
      Consecutive patients undergoing TAVI without predilatation using a self-expanding
      system at a single-center between April 2013 and December 2015 were followed up
      for one year and were retrospectively analyzed regarding mortality, safety and
      efficacy endpoints as well as common laboratory and echocardiographic parameters.
      RESULTS: A total of 164 patients (83+/-6 years; 56% female) were included in the
      analysis. According to the Valve Academic Research Consortium 2 (VARC-2) criteria
      the technical success rate was 96.3% and 89.1% of patients remained free of a
      combined safety endpoint at 30 days. Mortality rates at 30 days and 1 year were
      3.0% (n= 5) and 10.4% (n= 17), respectively. TAVI without predilatation was
      highly effective in lowering aortic valve peak velocity from 4.4 +/-0.6 m/s
      before to 1.7 +/-0.5 m/s (p <0.01), and mean pressure gradient across the valve
      from 48.7 +/-15.1 mmHg to 8.3+/-4.5 mmHg (<0.05). Left ventricular function
      remained unaltered after the intervention (51+/-10% prior to TAVI and 51+/-9%
      post TAVI), whereas high sensitive troponin T (hs-TnT), a well-established marker
      for myocardial injury, increased significantly from 26 ng/L (interquartile range
      = 18.00-44.00) to 119 ng/L (interquartile range = 73.25-166.00, p <0.001) during
      this time. Notably, an increase in the plasma levels of hs-TnT >15 times the
      upper limit of normal was associated with mortality both one month and one year
      after TAVI. CONCLUSIONS: TAVI without predilatation is feasible, safe and
      effective for aortic valve replacement in symptomatic patients with severe aortic
      stenosis who are at high perioperative risk. In contrast to a cohort of patients
      who underwent TAVI with predilatation previously published by another center, our
      patients did not suffer from transient impairment of left ventricular function.
      As a marker of myocardial injury, hs-TnT showed a less pronounced increase than
      reported previously. This might be a marker for a prognostic benefit as hs-TnT
      has been shown to be a strong predictor of outcome in patients undergoing TAVI.
      We conclude that direct TAVI is a less invasive option involving less myocardial
      stress.

PMID- 30303345
TI  - ?

PMID- 30303344
TI  - [CYTOKINE PROFILE IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION WITH AND WITHOUT
      COMPLICATIONS].
AB  - : The aim of this study was to evaluate the prognostic role of the cytokine
      profile in patients with ST segment elevation myocardial infarction (STEMI).
      Materials and methods: In the present paper we studied cytokines IL-6, IL-1beta,
      IL-10, TNFalpha and CRP in 81 patients with different course of STEMI. Results:
      In patients with complicated course of STEMI a significant increase in the
      concentration of IL-6, IL-10, FNOalpha, CRP was recorded on the 1st, 7th and 14th
      days compared with control group of healthy subjects and a group of patients with
      uncomplicated STEMI. Concentrations of TNFalpha>35.49 pg/ml, IL-6>33.37 pg/ml, IL
      10>34 pg/ml, CRP>10.84 mg/l on day 1 may suggest cardiovascular complications in
      STEMI patients within 1 year after the onset of the disease. We have not found
      reliable prognostic levels of IL-1beta, as the concentration of this cytokine
      remained within the accepted normal range.. Discussion: It is concluded that
      initially elevated levels of CRP l, TNFalpha, IL-6, IL-10 in the blood make it
      possible to identify groups of patients with myocardial infarction with ST
      segment elevation at high risk of cardiovascular events throughout the year.

PMID- 30303346
TI  - ?

PMID- 30303347
TI  - ?

PMID- 30303348
TI  - Comparative analysis of five-year outcomes of lower extremity varicose vein
      therapy using monopolar and segmental radiofrequency ablation.
AB  - BACKGROUND: To compare efficacy and safety of segmental and monopolar
      radiofrequency ablation in the management of lower extremity varicose veins.
      METHODS: 193 patients were treated with segmental RF ablation (Venefit; 97
      subjects) or monopolar RF ablation (EVRF; 96 subjects) for lower extremity
      varicose veins in 2010-2012. A single extremity of each patient with isolated GSV
      or SSV insufficiency was enrolled. The differences between the two groups in
      demographic parameters, disease severity, treated veins, peri- and postoperative
      complications, and treatment efficacy indicators (VCSS) were evaluated. RESULTS:
      Recanalisation rate at 5 years was 10.3% in Venefit group and 11.3% in EVFR group
      (p>.05). Varicose vein recurrence rates were 10.3% and 12.9% in the Venefit and
      EVFR groups, respectively (p>.05). The VCSS reduction was comparable between the
      two groups(p<.05). CONCLUSIONS: Venefit and EVRF systems can be considered
      equivalent in terms of efficacy and safety in the management of lower extremity
      varicose veins.

PMID- 30303349
TI  - [PROINFLAMMATORY CYTOKINES AND SIGNALING PATHWAYS IN PERIPHERAL BLOOD MONONUCLEAR
      CELLS IN PATIENTS WITH CORONARY ARTERY DISEASE].
AB  - Aim: To determine content of mononuclear ells (MNC) in peripheral blood of
      patients with coronary heart disease (CHD) and factors responsible for their
      functional state and cytokine production. Materials and methods: Concentration of
      proteinkinases JNK1/2, ERK1/2, MAPK38, AKT1, JAK2, FAK, AMPK, p70S6K, STAT3,
      STAT5B and STAT6 was determined in MNC lysate by immune-enzyme assay. Interleukin
      1beta, 2, 4 and y-interferon levels were measured in blood sera. Results: In
      patients with angina of effort and unstable angina, the JNK level was 59,8% and
      53,1% higher than the normal one respectively (r=0,013) and (r=0,012). The level
      of the nuclear transcription factor was 26,9% (r=0,015) and 27,9% (r=0,017), JAK2
      31,5% (r=0,022) and 48,6% (r=0,018), STAT3 49,6% (r=0,025) and 55,3% (r=0,02),
      STAT5B 21,5% (r=0,018) and 30,2% (r=0,011) lower. These changes were associated
      with a 13,1% (r=0,047) and 51,4% (r=0,019) rise in the STAT6 level, 30,1%
      (r=0,025) and 79,4% (r=0,003) FAK level, 7,6% (r=0,09) and 15,2% (r=0,039) AKT1
      level, 65,3 (r=0,02) and 76,2% (r=0,017) p70S6K level. Conclusion: Results of the
      study suggest persistent pro-inflammatory activation of whole blood cells in CHD
      patients due to enhanced levels of IL-1 and IL-2, components of the MAPK/SAPK
      signal pathway in MNC and decreased STAT3 level determining cell sensitivity to
      IL-10. The elevated intracellular level of ERK and JNK us responsible for high
      responsiveness of MNC to pro-inflammatory cytokines.

PMID- 30303350
TI  - ?

PMID- 30303351
TI  - ?

PMID- 30303352
TI  - [THE ROLE OF LOW-FREQUENCY PIEZOTHROMBOELASTOGRAPHY IN THE COMPREHENSIVE
      EVALUATION OF HEMOSTASIS IN CORONARY BYPASS SURGERY WITH CARDIOPULMONARY BYPASS].
AB  - Aim: To monitor the hemostatic system during platelet concentrate transfusions
      using low-frequency piezothromboelastography in patients with coronary bypass
      surgery given aspirin therapy. Materials and Methods: The study involved 148
      patients with coronary bypass surgery, with 76 ones undergoing intraoperative
      transfusion of platelet concentrate and 72 treated without transfusion. The
      control group consisted of 20 healthy individuals. In the perioperative period
      indicators of vascular-platelet, coagulation, anticoagulant and fibrinolytic
      components of hemostasis were evaluated by low-frequency pezotromboelastography
      using the ARP-01M "Mednord" hardware and software system (Russia). Results: It
      was shown that the antiplatelet effect of aspirin in the preoperative period was
      manifest as inhibition of the initial stage of blood coagulation accompanied by
      increased thrombin potential, the total gain of anticoagulant and fibrinolytic
      activity of the blood. Heart-lung bypass was accompanied by structural and
      chronometric anticoagulation, reduction of anticoagulation and increase of blood
      fibrinolytic activity. In the postoperative period, structural and chronometric
      anticoagulation was more pronounced in patients who did not undergo transfusion
      of platelet concentrate than in the group of patients with transfusion. Donor
      platelets further increased the blood hemostatic potential by neutralizing the
      antiplatelet effect of aspirin. Perioperative thrombohemorrhagic complications
      were absent in both groups. Conclusion: Low-frequency piezothromboelastography
      provides a tool for real-time monitoring the functional state of hemostasis
      system. Transfusion of platelet concentrate is not advisable given that the
      thrombin potential is preserved as confirmed by the results of low-frequency
      piezothromboelastography.

PMID- 30303353
TI  - ?

PMID- 30303354
TI  - ?

PMID- 30303355
TI  - Therapy for relapsed multiple myeloma.
AB  - Despite significant progress in our understanding and the development of novel
      therapies, most patients with multiple myeloma will experience relapse of their
      disease. Therapy of relapsed myeloma has improved due to the availability of
      novel agents that are highly active against the disease. However, the selection
      of therapy can be challenging due to the emergence of toxicities, comorbidities
      and frailty. In the following we discuss our approach to the treatment of the
      patient with relapsed myeloma.

PMID- 30303356
TI  - Pulmonary endoscopy emergencies.
AB  - In clinical practice, interventional pulmonologist faces several situations which
      can lead to dramatic consequences especially on ventilation and require immediate
      intervention. We describe the main pathological conditions where urgent
      bronchoscopy is crucial because they act through mechanisms such as airway
      obstruction or alteration of the anatomic integrity of the tracheobronchial tree.
      We point out the problems resulting from inhalation of foreign bodies, one of the
      most dramatic respiratory emergencies typical of childhood which needs not only
      the appropriate endoscopic equipment suitable for the age, but also great
      experience in the management of the possible related complications. Massive
      haemoptysis is then discussed in order to help choosing the right endoscope and
      to clarify the steps requested to face this dramatic event. Lastly, iatrogenic
      tracheal injuries are described, in spite of their low incidence. The correct
      endoscopic assessment of the lesions enables to select the proper therapeutic
      approach in multidisciplinary together with surgeons and anesthetists. Due to its
      peculiarities, emergency does not allow a classic training so it is difficult to
      estimate the procedure volume necessary to achieve an adequate endoscopic
      experience. We think, in this field, it is advisable referring to numbers
      proposed for elections endoscopic procedures. For these reasons, we consider
      desirable the use of simulators and clinic case discussions during interventional
      pulmonologists training.

PMID- 30303357
TI  - Childhood obesity.
AB  - Childhood obesity has assumed epidemic proportions and it is currently one of the
      most prevalent public health problems. The pathophysiology of excess weight gain
      is complex with interactions between genetic factors, environment and biological
      factors. In this review, we highlight the epidemiology of childhood obesity and
      discuss clinical evaluation of a child with obesity. A staged approach to
      treatment is detailed. We discuss the role of lifestyle modifications,
      pharmacotherapy and bariatric surgery as treatment strategies.

PMID- 30303358
TI  - [RESEARCH ON THE LEVEL, COMPONENTS AND THE TYPE OF COOPERATIVITY IN THE PATIENTS
      WITH ASTHMA].
AB  - The patient's cooperativity is the major factor which determines the patient's
      adherence to doctor's prescriptions and, consequently, the achievement of disease
      control. We proposed the "Evaluation of the cooperativity in asthma"
      questionnaire to evaluate the level, components and types of cooperativity in 141
      patients with the mixed or atopic form of asthma (94.3 and 5.7%, respectively) at
      admission to hospital who were aware about their disease. The analysis of
      investigated parameters depending on the level of patients' awareness of their
      condition (according to the "Awareness of patients about asthma" test), severity
      and duration of the disease, presence of alexithymia and social and economic
      index was done. It was found out that patients with asthma exaggerate the degree
      of their compliance. The general indices of cooperativity (GIC=58.1+/-7.3%) and
      understanding of danger (35.8+/-3.3%) in the patients who were aware about their
      disease were low. Qualitative characteristics of individual cooperativity
      components in examined patients are presented. Nearly 76% of the patients showed
      negative cooperativity inversely correlating with the severity of asthma and the
      duration of the disease. Positive cooperativity appeared to be directly related
      with the higher educational level, occupation and higher income level of the
      patients. Generally speaking, low average GIC ratings and low patients' adherence
      to asthma treatment suggest their low cooperativity.

PMID- 30303359
TI  - ?

PMID- 30303360
TI  - [THE PREVALENCE OF RESPIRATORY SYMPTOMS AMONG RESIDENTS OF THE RUSSIAN FAR
      NORTH].
AB  - Aim: To study the frequency of respiratory symptoms among the reindeer herders of
      the Yamal region in the Far North of Russia. We conducted a cross-sectional study
      of the occurrence of respiratory symptoms among 500 subjects of the tundra Nenets
      population (28.1% of the adult Nenets population in the district), of which 38.3%
      were men and 61.7% women (average age 40.1 years). All patients were matched for
      age and occupation. Medical examination was carried out by a pulmonologist with
      the use of the GARD questionnaire (WHO, 2004) and spirometry. Spirometry was
      performed with a SpiroUSB device (UK) according to a unified standard and the
      criteria of ATS/ERS 2005. The frequency of respiratory symptoms among the tundra
      population was estimated at 71.8%. Cough with expectoration and dyspnea were
      found in 22.8% of the respondents. 70.0% of the examined subjects worked in the
      cold, 33% were exposed to the open flame at home, and 34.4% smoked. Respiratory
      symptoms developed in 16.3% of those working in the cold and in 37% exposed to
      open fire. The combination of such complaints as cough and sputum production
      occurred in smokers twice as frequently as in non-smokers (54.1%) (p<0.01).The
      combination of such complaints as cough and sputum production was twice as likely
      note in his those who smoked (54.1% vs 20.2%) (p<0.01). The combination of these
      problems dyspnea was three times more common in the smokers (23,3%vs 7,3%)
      (p<0.001). At presence at patients of such a factor as work in the cold and the
      absence of other only 16.3% of them have respiratory symptoms. When using at home
      the open flame and the absence of other factors leading up 37.0% of the
      individuals with symptoms of chronic bronchitis. Cough, sputum and dyspnea are
      formed only among 26.3% of the smokers face when smoking is the only risk factor.
      If the surveyed residents of all three negative factors respiratory symptoms met
      at 62.1%. Disorders of respiratory function according to spirometry were not
      observed in none of the study participants. Respiratory symptoms developed in
      62.1% of the subjects exposed to all three risk factors. External respiration
      indices remain normal in all he examine subjects. It is concluded that residents
      of the Far North frequently suffer respiratory symptoms without disorders in the
      external respiratory function. In most cases they associated with three factors
      (work in the cold, exposure to open fire at home, and smoking). Compensatory
      stimulation of lung functions may create additional difficulties for diagnostics
      of bronchial obstruction.

PMID- 30303362
TI  - ?

PMID- 30303361
TI  - ?

PMID- 30303363
TI  - ?

PMID- 30303364
TI  - [RELATIONSHIP BETWEEN SMOKING AND INDICATORS OF SYSTEMIC INFLAMMATION IN PATIENTS
      WITH CORONARY HEART DISEASE].
AB  - Aim: To estimate the severity of systemic inflammation in subjects with coronary
      artery disease (CAD) without bronchopulmonary system comorbidity depending on
      smoking factor. Materials and methods: The subjects were divided into groups
      depending on smoking factor. We estimated the following laboratory markers of
      nonspecific inflammation: interleukine (IL)-12, -1beta, tumour necrosis factor
      alpha, matrix metalloproteinase-9, C-reactive protein. The examination of lungs
      respiratory function included spirometry, body plethysmography and assessment of
      diffusing lung capacity. Results: 29.9% of the subjects with CAD smoked, 40%
      reported discontinuation of smoking in their histories. Smoking in CAD subjects
      without the history of bronchopulmonary system comorbidity was associated with a
      higher level of inflammatory markers (IL-12, IL-1beta, TNF-alpha, MMR-9 and CRP)
      than in subjects who ceased to smoke and those who have never smoked. No
      differences in the levels of inflammatory markers were revealed in subjects who
      had smoked before and never smoked. Conclusion: Smoking is widespread among CAD
      subjects. It is associated with a higher level of markers of nonspecific
      inflammation as compared to subjects who have never smoked before or ceased
      smoking.

PMID- 30303365
TI  - DNA-Functionalized Porous Fe3O4 Nanoparticles for the Construction of Self
      Powered miRNA Biosensor with Target Recycling Amplification.
AB  - Herein, we have developed an ultrasensitive self-powered biosensor for miRNA
      assay based on biofuel cells. The system is composed of indium tin oxide cathode
      and graphene oxide/gold nanoparticle/glucose oxidase anode. Redox probe of
      [Fe(CN)6]3- is entrapped inside porous Fe3O4 nanoparticles by DNA. However, in
      the presence of target miRNA, hybridization reaction occurs between miRNA and
      DNA, which initiates the release of [Fe(CN)6]3-. Moreover, duplex specific
      nuclease is further employed to trigger target recycling amplification. As a
      result, much more redox probes are released and the open circuit voltage is
      significantly increased. A "signal-on" self-powered biosensor for miRNA
      quantification is thus developed. The detection range is from 10 aM to 10 fM;
      meanwhile, the limit of detection is as low as 1.4 aM, which is superior to that
      in most reported methods. Therefore, the proposed biosensor is expected to be a
      powerful point-of-care tool for miRNA diagnostics, which may have wide
      applications in the future.

PMID- 30303366
TI  - Unraveling the Photodeprotection Mechanism of Anthraquinon-2-ylmethoxycarbonyl
      Caged Alcohols Using Time-Resolved Spectroscopy.
AB  - Anthraquinone (AQ) compounds have been used as photolabile protecting groups
      (PPGs) to protect alcohols, ketones, and carboxylic acids. However, because of
      the lack of direct spectroscopic information for the transient species and
      intermediates related with the deprotection reaction(s), the photorelease
      mechanism(s) of these systems are still largely unknown. In this contribution, we
      detail a time-resolved spectroscopic investigation using anthraquinone-protected
      galactose (1) and adenosine (2) to investigate the photodeprotection reaction
      mechanism(s) of these kinds of AQ-PPGs. It was found that, in THF-H2O solvents,
      the ketyl radical species generated for 1 and 2 was found to be a reactive
      intermediate that then formed a dihydroxyanthracene species. The
      photodeprotection then occurred with the accompaniment of a decarboxylation
      process. These results provide an improved understanding for how AQ-PPGs work and
      will help assist in the design and applications of selected anthraquinone
      derivatives as a PPG platform, especially in aqueous environments more relevant
      for use in biological systems.

PMID- 30303367
TI  - Allosteric Inhibition of a Mammalian Lectin.
AB  - Glycan-binding proteins are key components of central physiological and cellular
      processes such as self-/non-self-recognition, cellular tissue homing, and protein
      homeostasis. Herein, C-type lectins are a diverse protein family that play
      important roles in the immune system, rendering them attractive drug targets. To
      evaluate C-type lectin receptors as target proteins for small-molecule effectors,
      chemical probes are required, which are, however, still lacking. To overcome the
      supposedly poor druggability of C-type lectin receptors and to identify starting
      points for chemical probe development, we screened murine langerin using 1H and
      19F NMR against a library of 871 drug-like fragments. Subsequently, hits were
      validated by surface plasmon resonance and enzyme-linked lectin assay. Using
      structure-activity relationship studies and chemical synthesis, we identified
      thiazolopyrimidine derivatives with double-digit micromolar activity that
      displayed langerin selectivity. Based on 1H-15N HSQC NMR and competitive binding
      and inhibition experiments, we demonstrate that thiazolopyrimidines
      allosterically inhibit langerin. To the best of our knowledge, this is the first
      report of drug-like allosteric inhibitors of a mammalian lectin.

PMID- 30303368
TI  - Inverse Sandwich Cyclopentadienyl Complexes of Sodium in the Gas Phase.
AB  - Infrared multiple photon dissociation (IRMPD) experiments and electronic
      structure computations have been used to explore the structures and energetics of
      binding in gas phase sodium cyclopentadienyl complexes of the general form Na nCp
      n-1+. Computational work for the analogous anionic Na nCp n+1- complexes reveals
      nearly identical energetics for the loss of neutral NaCp units from both cationic
      and anionic species leading to the conclusion that the binding in the gas phase
      species is largely electrostatic, arising primarily from ion-ion and ion-dipole
      interactions. This is supported by an examination of the molecular orbitals of
      these species, which show no orbital overlap between the Na and Cp moieties.
      Observation of peaks in the IRMPD spectra, which do not correspond to any of the
      computed linear absorption frequencies, strongly suggest the contribution of
      overtone and combination bands.

PMID- 30303369
TI  - I2-Mediated Iodobenzannulation of Yne-Allenones toward 1-Naphthols and Their
      Synthetic Application.
AB  - A new I2-mediated iodobenzannulation of yne-allenones has been established,
      enabling breaking/rearranging of C=C bonds to selectively access 4-iodonaphthalen
      1-ols with generally good yields. The resulting 4-iodonaphthalen-1-ols could
      serve as a new and reliable coupling reagent, which further reacted with H2O
      under the oxygen conditions to generate unexpected 1,2-carbonyls with good yields
      through Pd-catalyzed deiodinated carbonylation, whereas employment of benzene-1,2
      diamine as the nucleophile rendered 3-(quinoxalin-2-yl)naphthalen-1-ols through
      Pd-catalyzed [4 + 2] heterocyclization. On the basis of the controlled
      experiments, the mechanism for forming 1,2-carbonyls was proposed, including an
      oxidative addition, 1,3-palladium migration, reductive elimination, and oxidative
      dehydrogenation sequence.

PMID- 30303370
TI  - Highly Reliable Superhydrophobic Protection for Organic Field-Effect Transistors
      by Fluoroalkylsilane-Coated TiO2 Nanoparticles.
AB  - One of the long-standing problems in the field of organic electronics is their
      instability in an open environment, especially their poor water resistance. For
      the reliable operation of organic devices, introducing an effective protection
      layer using organo-compatible materials and processes is highly desirable. Here,
      we report a facile method for the depositing of an organo-compatible
      superhydrophobic protection layer on organic semiconductors under ambient
      conditions. The protection layer exhibiting excellent water-repellent and self
      cleaning properties was deposited onto organic semiconductors directly using a
      dip-coating process in a highly fluorinated solution with fluoroalkylsilane
      coated titanium dioxide (TiO2) nanoparticles. The proposed protection layer did
      not damage the underlying organic semiconductors and had good resistance against
      mechanical-, thermal-, light-stress-, and water-based threats. The protected
      organic field-effect transistors exhibited more-reliable electrical properties,
      even when exposed to strong solvents, due to its superhydrophobicity. This study
      provides a practical solution with which to enhance the reliability of
      environmentally sensitive organic semiconductor devices in the natural
      environment.

PMID- 30303371
TI  - Three Alumino/Galloborate Frameworks Templated by Organic Amines: Syntheses,
      Structures, and Nonlinear Optical Properties.
AB  - A series of alumino/galloborates, including (H3APEA)6[Al-B5O10]9.12H2O (1, APEA =
      N, N'-bis(3-aminopropyl)ethylenedi-amine), (HDETA)2(H2DETA)2[AlB5O10]3 (2, DETA =
      diethylenetriamine), and (H2EDAP)[GaB5O10].H2O (3, EDAP = N-ethyl
      diaminopropane), was solvothermally synthesized and characterized in solid-state
      by powder X-ray diffraction, Fourier transform infrared spectroscopy, UV-vis
      spectroscopy, and single-crystal X-ray diffraction. All of them feature the
      [MB5O10] n2 n- (M = Al or Ga) frameworks, charge-balanced by the long chain-like
      amine cations. Three frameworks exhibit different interlinkage modes of {MB5O10}
      layers, resulting in channels varying in size and shape. The flexibility of long
      chain-like amine cations as well as their significant structure-directing
      functions in forming these crystalline products is also discussed in detail.
      Powder second-harmonic generation measurements showed that all three compounds
      present a nonlinear optical property, and compound 2 exhibits type I phase
      matchable optical nonlinearity.

PMID- 30303372
TI  - A High-Resolution Spatial Model to Predict Exposure to Pharmaceuticals in
      European Surface Waters: ePiE.
AB  - Environmental risk assessment of pharmaceuticals requires the determination of
      their environmental exposure concentrations. Existing exposure modeling
      approaches are often computationally demanding, require extensive data collection
      and processing efforts, have a limited spatial resolution, and have undergone
      limited evaluation against monitoring data. Here, we present ePiE (exposure to
      Pharmaceuticals in the Environment), a spatially explicit model calculating
      concentrations of active pharmaceutical ingredients (APIs) in surface waters
      across Europe at ~1 km resolution. ePiE strikes a balance between generating data
      on exposure at high spatial resolution while having limited computational and
      data requirements. Comparison of model predictions with measured concentrations
      of a diverse set of 35 APIs in the river Ouse (UK) and Rhine basins (North West
      Europe), showed around 95% were within an order of magnitude. Improved
      predictions were obtained for the river Ouse basin (95% within a factor of 6; 55%
      within a factor of 2), where reliable consumption data were available and the
      monitoring study design was coherent with the model outputs. Application of ePiE
      in a prioritisation exercise for the Ouse basin identified metformin, gabapentin,
      and acetaminophen as priority when based on predicted exposure concentrations.
      After incorporation of toxic potency, this changed to desvenlafaxine, loratadine,
      and hydrocodone.

PMID- 30303373
TI  - Correction to Dynamic Sparse Sampling for Confocal Raman Microscopy.

PMID- 30303374
TI  - Concentrations of Organophosphate Esters and Their Specific Metabolites in Food
      in Southeast Queensland, Australia: Is Dietary Exposure an Important Pathway of
      Organophosphate Esters and Their Metabolites?
AB  - There were several studies that measured organophosphate esters (OPEs) in foods
      to assess the dietary intake of OPEs but none has measured OPE metabolites
      (mOPEs) in the same samples. In this study, we measured the concentrations of
      OPEs and mOPEs in 87 food samples and in five tap water samples collected in
      Queensland, Australia belonging to eight food groups. Tris(2-chloroisopropyl)
      phosphate (TCIPP) (detection frequency (DF), 77%) and tributyl phosphate (TBP)
      (DF, 71%), were the most frequently detected OPEs, while dibutyl phosphate (DBP)
      (DF, 84%) and diphenyl phosphate (DPhP) (DF, 86%) were the most frequently
      detected mOPEs. Vegetables had the highest concentrations of both ?9OPEs and
      ?11mOPEs, with the mean concentrations of 2.6 and 17 ng/g wet weight. Compared
      with dust ingestion and inhalation, dietary intake was the most important
      exposure pathway for tris(2-chloroethyl) phosphate (TCEP) (4.1 ng/kg bw/day),
      TCIPP (25 ng/kg bw/day), and TBP (6.7 ng/kg bw/day), accounting for >75% of total
      intake. Furthermore, we found that the intakes of some mOPEs, that is, bis(1,3
      dichloroisopropyl) phosphate (BDCIPP) and DPhP from diet were typically higher
      than that of their parent OPEs. Such high levels of mOPE intakes could interfere
      with the utilization of mOPEs as biomarkers for assessing OPE exposure and
      warrant further investigation.

PMID- 30303375
TI  - Free-Radical-Promoted Copper-Catalyzed Intermolecular Cyanosulfonylation and
      Cyanotrifluoromethylation of Unactivated Alkenes in Water-Containing Solvents.
AB  - A novel and practical copper-catalyzed strategy for intermolecular
      cyanosulfonylation and cyanotrifluoromethylation of unactivated alkenes in water
      containing solvents is described. The methodology developed provides an efficient
      and convenient access to a variety of beta-sulfonyl nitriles and beta
      trifluoromethyl nitriles, which would have wide applications in chemical and
      pharmaceutical industries.

PMID- 30303376
TI  - An Approach to the 9-Oxo-10-oxabicyclo[5.3.0]dec-2-ene Core of the Guaianolide
      and Pseudoguaianolide Sesquiterpenes via a Domino Electrocyclic Ring
      Opening/Carboxylic Acid Trapping of a gem-Dibromocyclopropane.
AB  - A domino silver(I)-promoted electrocyclic 2pi-disrotatory electrocyclic ring
      opening/intramolecular nucleophilic trapping of [ n.1.0]-dibromocyclopropanes by
      tethered carboxylic acids results in cyclization to butyrolactones fused to six-
      and seven-membered carbocycles. In the case of bicyclic [4.3.0] lactones the cis
      fused stereoisomer was formed, whereas for the bicyclic [5.3.0] lactones the
      trans-fused stereoisomer was formed. Optimal conditions for the reaction used
      silver(I) trifluoroacetate (2.0 equiv) in trifluoroethanol or with added pyridine
      (2.0 equiv) and NaPF6 (5.0 equiv). The dibromocyclopropane precursors were made
      through cyclopropanation with in situ-generated dibromocarbene. The trans-fused
      lactones are potentially useful building blocks for pseudoguaianolide,
      guaianolide, and xanthanolide total synthesis. A computational study on the
      conformational preferences of these systems indicates that the trans-fused
      bicyclic [5.3.0] butyrolactones are lower in energy than the corresponding cis
      fused lactones at the B3LYP/cc-pVTZ level of theory.

PMID- 30303377
TI  - Fast Pairwise Approximation of Solvent Accessible Surface Area for Implicit
      Solvent Simulations of Proteins on CPUs and GPUs.
AB  - We propose a pairwise and readily parallelizable SASA-based nonpolar solvation
      approach for protein simulations, inspired by our previous pairwise GB polar
      solvation model development. In this work, we developed a novel function to
      estimate the atomic and molecular SASAs of proteins, which results in comparable
      accuracy as the LCPO algorithm in reproducing numerical icosahedral-based SASA
      values. Implemented in Amber software and tested on consumer GPUs, our pwSASA
      method reasonably reproduces LCPO simulation results, but accelerates MD
      simulations up to 30 times compared to the LCPO implementation, which is greatly
      desirable for protein simulations facing sampling challenges. The value of
      incorporating the nonpolar term in implicit solvent simulations is explored on a
      peptide fragment containing the hydrophobic core of HP36 and evaluating thermal
      stability profiles of four small proteins.

PMID- 30303378
TI  - A Highly Reduced Ni-Li-Olefin Complex for Catalytic Kumada-Corriu Cross
      Couplings.
AB  - The catalytic activity of a highly reduced Ni catalyst in the context of a Kumada
      Corriu cross-coupling has been studied. This nickel complex is characterized by
      its high electron density, stabilized by simple olefin ligands in combination
      with two Li ions. Landmark reactivity has been found with this precatalyst which
      operates at cryogenic temperatures, thus allowing the presence of sensitive
      functionalities. Structural elucidation of oxidative addition intermediates and
      their reactivity suggest highly reduced species being operative in the C-C bond
      forming event.

PMID- 30303379
TI  - Ti-Catalyzed Radical Alkylation of Secondary and Tertiary Alkyl Chlorides Using
      Michael Acceptors.
AB  - Alkyl chlorides are common functional groups in synthetic organic chemistry.
      However, the engagement of unactivated alkyl chlorides, especially tertiary alkyl
      chlorides, in transition-metal-catalyzed C-C bond formation remains challenging.
      Herein, we describe the development of a TiIII-catalyzed radical addition of 2
      degrees  and 3 degrees  alkyl chlorides to electron-deficient alkenes.
      Mechanistic data are consistent with inner-sphere activation of the C-Cl bond
      featuring TiIII-mediated Cl atom abstraction. Evidence suggests that the active
      TiIII catalyst is generated from the TiIV precursor in a Lewis-acid-assisted
      electron transfer process.

PMID- 30303380
TI  - Isomerism in Supramolecular Adducts of Atomically Precise Nanoparticles.
AB  - We present isomerism in a few supramolecular adducts of atomically precise
      nanoparticles, [Ag29(BDT)12?(CD) n]3- ( n = 1-6), abbreviated as I where BDT and
      CD are 1,3-benzenedithiol and cyclodextrins (alpha, beta and gamma),
      respectively; ? symbolizes an inclusion complex. The different host-guest
      complexes of I were characterized in the solution state as well as in the gas
      phase. The CDs (alpha, beta and gamma) encapsulate a pair of BDT ligands
      protecting the Ag29 core. This unique geometry of the supramolecular adducts
      makes the system similar to octahedral complexes of transition metals, which
      manifest various isomers. These isomers of I ( n = 2-4) were separated by ion
      mobility mass spectrometry (IM MS). We proposed structures of all the inclusion
      complexes with the help of IM MS measurements and molecular docking, density
      functional theory (DFT), and collision cross section (CCS) calculations.

PMID- 30303381
TI  - Thermal Evolution of ZnS Nanostructures: Effect of Oxidation Phenomena on
      Structural Features and Photocatalytical Performances.
AB  - ZnS nanosystems are being extensively studied for their possible use in a wide
      range of technological applications. Recently, the gradual oxidation of ZnS to
      ZnO was exploited to tune their structural, electronic, and functional
      properties. However, the inherent complexity and size dependence of the ZnS
      oxidation phenomena resulted in a very fragmented description of the process. In
      this work, different-sized nanosystems were obtained through two different low
      temperature wet chemistry routes, namely, hydrothermal and inverse miniemulsion
      approaches. These protocols were used to obtain ZnS samples consisting of 21 and
      7 nm crystallites, respectively, to be used as reference material. The obtained
      samples were then calcinated at different temperatures, ranging from 400 to 800 
      degrees C toward the complete oxidation of ZnO, passing through the coexistence
      of the two phases (ZnS/ZnO). A thorough comparison of the effects of thermal
      handling on ZnS structural, chemical, and functional evolution was carried out by
      TEM, XRD, XAS, XPS, Raman, FT-IR, and UV-Vis. Finally, the photocatalytic
      activity in the H2 evolution reaction was also compared for selected ZnS and
      ZnS/ZnO samples. A correlation between size and the oxidation process was
      observed, as the smaller nanosystems showed the formation of ZnO at lower
      temperature, or in a larger amount in the case of the ZnS and ZnO co-presence. A
      difference in the underlying mechanism of the reaction was also evidenced.
      Despite the ZnS/ZnO mixed samples being characterized by an increased light
      absorption in the visible range, their photocatalytic activity was found to be
      much lower.

PMID- 30303382
TI  - Theionbrunonines A and B: Dimeric Vobasine Alkaloids Tethered by a Thioether
      Bridge from Mostuea brunonis.
AB  - Theionbrunonines A and B (1 and 2), the first examples of monoterpene bisindole
      alkaloids linked by a thioether bridge, were isolated from the stems of Mostuea
      brunonis, guided by a molecular networking-based dereplication strategy. Their
      structures were elucidated by a combination of spectroscopic data and ECD
      calculations. A plausible biosynthetic pathway for 1 and 2 was postulated.
      Theionbrunonines A and B (1 and 2) showed moderate antiplasmodial activities in
      the micromolar range against the strain FcB1 of Plasmodium falciparum and no
      cytotoxic activity against the MRC-5 cell line at 20 MUM.

PMID- 30303383
TI  - Experimental Characterization of Droplet Adhesion: The Ejection Test Method (ETM)
      Applied to Surfaces with Various Hydrophobicity.
AB  - We study the wetting and the adhesive behavior of substrates made by
      electropolymerization of copolymers of pyrene substituted with fluoroalkyl and
      adamantyl groups. The hydrophobicity and water adhesion properties can be tuned
      by the molar percentage (mol %) of each pyrene monomer so that the substrate
      properties can vary from superhydrophobic to parahydrophobic, with respectively
      low and high water adhesion. The ejection test method (ETM) is proposed as an
      original tool to discriminate and characterize such substrates. Using a catapult
      like apparatus, a droplet initially at rest on the surface is subject to a large
      acceleration and is subsequently ejected. Depending on the surface properties and
      initial catapult acceleration, the ejection is more or less efficient and occurs
      with or without fragmentation of the droplet. The ETM is shown to be a
      complementary test to the lateral adhesion and hysteresis classical measurements.
      This work is of importance for the understanding of adhesion phenomena on various
      surfaces and for a better quantitative characterization of their adhesive
      properties.

PMID- 30303384
TI  - G-Quadruplex-Based Nanoscale Coordination Polymers to Modulate Tumor Hypoxia and
      Achieve Nuclear-Targeted Drug Delivery for Enhanced Photodynamic Therapy.
AB  - Photodynamic therapy (PDT) is a light-triggered therapy used to kill cancer cells
      by producing reactive oxygen species (ROS). Herein, a new kind of DNA
      nanostructure based on the coordination between calcium ions (Ca2+) and AS1411
      DNA G quadruplexes to form nanoscale coordination polymers (NCPs) is developed
      via a simple method. Both chlorine e6 (Ce6), a photosensitizer, and hemin, an
      iron-containing porphyrin, can be inserted into the G-quadruplex structure in the
      obtained NCPs. With further polyethylene glycol (PEG) modification, we obtain Ca
      AS1411/Ce6/hemin@pHis-PEG (CACH-PEG) NCP nanostructure that enables the
      intranuclear transport of photosensitizer Ce6 to generate ROS inside cell nuclei
      that are the most vulnerable to ROS. Meanwhile, the inhibition of antiapoptotic
      protein B-cell lymphoma 2 (Bcl-2) expression by AS1411 allows for greatly
      improved PDT-induced cell apoptosis. Furthermore, the catalase-mimicking DNAzyme
      function of G-quadruplexes and hemin in those NCPs could decompose tumor
      endogenous H2O2 to in situ generate oxygen so as to further enhance PDT by
      overcoming the hypoxia-associated resistance. This work develops a simple yet
      general method with which to fabricate DNA-based NCPs and presents an interesting
      concept of a nanoscale drug-delivery system that could achieve the intranuclear
      delivery of photosensitizers, the down-regulation of anti-apoptotic proteins, and
      the modulation of the unfavorable tumor microenvironment simultaneously for
      improved cancer therapy.

PMID- 30303386
TI  - Stereoselective Allylic Alkylation of 1-Pyrroline-5-carboxylic Esters via a Pd/Cu
      Dual Catalysis.
AB  - The asymmetric allylation of 1-pyrroline-5-carboxylic esters has been
      accomplished through a synergistic Pd/Cu catalyst system under mild reaction
      conditions. The mechanistic studies suggested that (1) nucleophilic attack is the
      enantiodiscriminating step; (2) the cooperative action of two chiral reactive
      species, N-metalated azomethine ylides and pi-allylpalladium, is most likely
      responsible for its high reactivity and excellent enantioselectivity (up to >99%
      ee); and (3) the steric hindrance and electronic factors of the allylic
      electrophiles and imino ester substrates are crucial for the formation of the
      linear products. A series of 3,4-2 H-pyrrole derivatives bearing a quaternary
      stereogenic center were easily synthesized in high yields and with high to
      excellent regioselectivity and enantioselectivity.

PMID- 30303385
TI  - Combining Mass Spectrometry and NMR Improves Metabolite Detection and Annotation.
AB  - Despite inherent complementarity, nuclear magnetic resonance spectroscopy (NMR)
      and mass spectrometry (MS) are routinely separately employed to characterize
      metabolomics samples. More troubling is the erroneous view that metabolomics is
      better served by exclusively utilizing MS. Instead, we demonstrate the importance
      of combining NMR and MS for metabolomics by using small chemical compound
      treatments of Chlamydomonas reinhardtii as an illustrative example. A total of
      102 metabolites were detected (82 by gas chromatography-MS, 20 by NMR, and 22 by
      both techniques). Out of these, 47 metabolites of interest were identified: 14
      metabolites were uniquely identified by NMR, and 16 metabolites were uniquely
      identified by GC-MS. A total of 17 metabolites were identified by both NMR and GC
      MS. In general, metabolites identified by both techniques exhibited similar
      changes upon compound treatment. In effect, NMR identified key metabolites that
      were missed by MS and enhanced the overall coverage of the oxidative pentose
      phosphate pathway, Calvin cycle, tricarboxylic acid cycle, and amino acid
      biosynthetic pathways that informed on pathway activity in central carbon
      metabolism, leading to fatty-acid and complex-lipid synthesis. Our study
      emphasizes a prime advantage of combining multiple analytical techniques: the
      improved detection and annotation of metabolites.

PMID- 30303387
TI  - Modified Pluronic F127 Surface for Bioconjugation and Blocking Nonspecific
      Adsorption of Microspheres and Biomacromolecules.
AB  - Many experiments and applications require the chemical coupling of target
      molecules to surfaces, during which the elimination of nonspecific interactions
      presents a difficult challenge. We report on a technologically accessible surface
      passivation and chemical conjugation method based on an NHS end-labeled F127
      Pluronic block copolymer (F127-NHS). To quantify interactions between the F127
      NHS surface and magnetic microspheres, we developed a simple assay: the
      microsphere adhesion by gravity, inversion, then counting, or "MAGIC" assay. To
      improve blocking of microspheres while maintaining the ability to chemically
      couple additional molecules, we implemented a pH-dependent two-step chemical
      modification process for amine microspheres. This process achieves an extremely
      high level of blocking nonspecific interactions (less than 2% nonspecific
      adhesion) for a variety of microsphere surface charges and chemical
      functionalities. We also demonstrate the ability to specifically tether magnetic
      microspheres to an F127-NHS surface, using single DNA molecules. Using the DNA
      microspheres, we establish the applicability of the surface for force
      spectroscopy (stable with an applied load >30 pN) via the massively parallel
      technique of centrifuge force microscopy. Finally, we demonstrate that the
      surface can be used in fluorescence studies with a fluorogenic peptide cleavage
      assay, with high levels of blocking achieved for both the fluorogenic peptide and
      trypsin. These results suggest applications including, but not limited to, single
      molecule force spectroscopy and fluorescence, biosensors, medical implants, and
      anti-biofouling, which could make use of the F127-NHS surface.

PMID- 30303388
TI  - Highly Selective Synthesis of Pillar[ n]arene ( n = 5, 6).
AB  - An efficient and highly selective synthetic method toward the preparation of
      pillar[ n]arenes ( n = 5, 6) is reported, based upon a high solvent-dependent
      selectivity found in the condensation reaction between 1,4-dialkyloxybenzene and
      paraformaldehyde, involving methanesulfonic acid as catalyst. Pillar[6]arene (P6)
      is obtained as the major product when using chloroform as solvent, while in
      dichloromethane pillar[5]arene (P5) is the dominant product. Accordingly, a
      series of P5 and P6 have been selectively synthesized with excellent yield.

PMID- 30303389
TI  - Macrolactonization of Alkynyl Alcohol through Rh(I)/Yb(III) Catalysis.
AB  - A catalytic macrolactonization through oxidative cyclization of alkynyl alcohol
      by synergistic transition-metal and Lewis-acid catalysis was developed. Because
      the alkynyl alcohol substrates involved in this method are different from the
      seco acids that are used in conventional macrolactonization methods, the current
      method provides a strategically distinct entry to macrolactones. In addition to
      the operational simplicity, this macrolactonization protocol proceeds at
      relatively high concentration, precluding the need for high dilution or slow
      addition procedures.

PMID- 30303390
TI  - Osmotic Shock-Triggered Assembly of Highly Charged, Nanoparticle-Supported
      Membranes.
AB  - Spherical nanoparticle-supported lipid bilayers (SSLBs) combine precision
      nanoparticle engineering with biocompatible interfaces for various applications,
      ranging from drug delivery platforms to structural probes for membrane proteins.
      Although the bulk, spontaneous assembly of vesicles and larger silica
      nanoparticles (>100 nm) robustly yields SSLBs, it will only occur with low charge
      density vesicles for smaller nanoparticles (<100 nm), a fundamental barrier in
      increasing SSLB utility and efficacy. Here, through whole mount and cryogenic
      transmission electron microscopy, we demonstrate that mixing osmotically loaded
      vesicles with smaller nanoparticles robustly drives the formation of SSLBs with
      high membrane charge density (up to 60% anionic lipid or 50% cationic lipid). We
      show that the osmolyte load necessary for SSLB formation is primarily a function
      of absolute membrane charge density and is not lipid headgroup-dependent,
      providing a generalizable, tunable approach toward bulk production of highly
      curved and charged SSLBs with various membrane compositions.

PMID- 30303391
TI  - Stereocontrolled Nucleophilic Fluorination at the Tertiary sp3-Carbon Center for
      Enantiopure Synthesis of 3-Fluorooxindoles.
AB  - The first asymmetric nucleophilic fluorination at the sp3-tertiary carbon center
      has been developed using inexpensive tetrabutylammonium fluoride (TBAF) without
      any metal/catalyst for the synthesis of 3-fluoro-3-substituted oxindoles with
      excellent enantioselectivity (ee up to >99%). Regio- and stereocontrolled ring
      opening of spiroaziridine with retention of configuration and other experiments
      revealed that the fluorination proceeded through an anchimeric assistance.

PMID- 30303392
TI  - Solid-State 31P Nuclear Magnetic Resonance Study of Interlayer Hydroxide Surfaces
      of Kaolinite Probed with an Interlayer Triethylphosphine Oxide Monolayer.
AB  - The solid acidity of the interlayer aluminol surfaces of kaolinite was explored
      by solid-state 31P nuclear magnetic resonance with magic angle spinning (MAS)
      using triethylphosphine oxide (TEPO), which formed a monolayer with a uniform
      orientation between the layers of kaolinite as a probe molecule. Intercalation of
      TEPO between the layers of kaolinite was achieved using methoxy-modified
      kaolinite as an intermediate. The presence of TEPO in the reaction products was
      revealed by the two signals at 21 and 7 ppm, which were assignable to ethyl
      groups in TEPO, in the solid-state 13C nuclear magnetic resonance with cross
      polarization and magic angle spinning techniques (13C CP/MAS NMR). The presence
      of TEPO between the layers of kaolinite was demonstrated by the expansion of
      basal spacing from 0.86 nm, the interlayer distance of methoxy-modified kaolinite
      to 1.16 nm, as shown by the X-ray diffraction patterns, suggesting the formation
      of a TEPO monolayer between the layers of kaolinite. The formation of hydrogen
      bonds between the P?O groups of TEPO and the aluminol groups on the interlayer
      surfaces of kaolinite was also revealed by the appearance of an additional OH
      stretching band at 3598 cm-1 in the Fourier-transform infrared spectrum and
      narrow solid-state 31P MAS NMR signals observed at 55-53 ppm which were shifted
      from the position of the physisorbed TEPO (50 ppm). These results clearly
      indicate that the solid acidity of interlayer aluminol groups of methoxy-modified
      kaolinite was probed using an interacted TEPO monolayer.

PMID- 30303393
TI  - Influence of pH and Salt Concentration on Pickering Emulsions Stabilized by
      Colloidal Peanuts.
AB  - Solid-stabilized emulsions commonly known as Pickering emulsions offer unique
      benefits such as superior stability and controlled permeability compared to
      conventional surfactant stabilized emulsions. In this article, the effect of pH,
      the electrolyte and particle concentration, homogenization speed, and volume
      fraction of oil on the formation, stability, and the microstructure of emulsion
      droplets stabilized by micron-size peanut-shaped hematite particles are
      investigated. The influence of surface charge of particles on emulsification is
      studied by varying the pH of the dispersing medium, the addition of an
      electrolyte or a combination of both. Stable O/W emulsions are formed only when
      the aqueous dispersions at intermediate pH between 4 and 11, and decane (2:1
      volume ratio) are vigorously mixed. However, emulsions are not formed when the
      particles are highly charged that is, at pH 2 and 12. The presence of monovalent
      salt or high-speed homogenization assists the emulsion formation at pH 3, whereas
      their combination helps in emulsification at pH 2. However, neither the addition
      of an electrolyte nor the high-speed homogenization or their combination
      facilitates the formation of emulsions at pH 12. We show that the image-charge
      repulsion and the surface charge induced wettability change can explain the
      influence of both pH and salt concentrations on the formation of Pickering
      emulsions. Although oil-in-water emulsions typically cream because of the density
      difference, microscopy observations revealed the presence of a large number of
      small particle-covered oil droplets in the sediments of the emulsified samples.
      These drops are observed to be entrapped in dense-particle networks. This leads
      to a considerable reduction in the number of particles available for the
      stabilization of floating emulsion droplets and thus influences their size and
      surface coverage. The possibility of tailoring the stability, droplet size and,
      the surface coverage discussed in this article can play a crucial role in
      situations that demand controlled release of active components.

PMID- 30303394
TI  - Memory training for adults with probable mild cognitive impairment: a pilot
      study.
AB  - BACKGROUND & OBJECTIVES: This pilot study aimed to evaluate the efficacy of
      memory training and health training intervention over a 24-month period in people
      with probable mild cognitive impairment (MCI). RESEARCH DESIGN & METHODS: Based
      on the accepted criteria, and the neuropsychiatric measures used in the trial,
      MCI was defined as a subjective change in cognition, impairment in episodic
      memory, preservation of independence of functional abilities, and no dementia.
      Without a neurological assessment, laboratory tests, and psychometric evaluation
      combined, some of our participants may have had dementia that we were unable to
      detect through neuropsychological testing. Of the 263 total participants, 39 met
      criteria for a diagnosis of MCI. There were 19 adults in the memory and 20 in
      health training conditions. Both groups received twenty hours of classroom
      content that included eight hours of booster sessions at three months post
      intervention. Hierarchical linear models (HLM) and standardized regression-based
      (SBR) analyses were used to test the efficacy of the intervention on immediate
      recall, delayed recall, subjective memory complaints, and memory self-efficacy.
      Age, education, depression, racial group, ethnic group, MMSE score, and baseline
      performance were included as covariates. RESULTS: Over 24 months, the MCI group
      in the memory training condition showed better objective and subjective memory
      outcomes compared with the MCI group in the health training condition.
      CONCLUSIONS: Senior WISE Memory training delivered to individuals with MCI was
      able to forestall the participants' declining cognitive ability and sustain the
      benefit over two years in both subjective and objective memory function.

PMID- 30303395
TI  - Early Pulmonary Vascular Disease in Preterm Infants is Associated with Late
      Respiratory Outcomes in Childhood.
AB  - RATIONALE: Early pulmonary vascular disease (PVD) after preterm birth is
      associated with a high risk for developing bronchopulmonary dysplasia (BPD), but
      its relationship with late respiratory outcomes during early childhood remains
      uncertain. OBJECTIVE: To determine whether PVD at 7 days after preterm birth is
      associated with late respiratory disease (LRD) during early childhood. METHODS:
      Prospective study of preterm infants born before 34 weeks postmenstrual age
      (PMA). Echocardiograms were performed at 7 days and 36 weeks PMA. Prenatal and
      early postnatal factors and post-discharge follow-up survey data obtained at 6,
      12,18, and 24 months of age were analyzed in logistic regression models to
      identify early risk factors for LRD, defined as a physician diagnosis of asthma,
      reactive airways disease, BPD exacerbation, bronchiolitis, or pneumonia, or a
      respiratory-related hospitalization during follow-up. RESULTS: Of the 221
      subjects (median 27 weeks PMA; IQR: 25-28 and 920g; IQR: 770g-1090g) completing
      follow-up, 61% met LRD criteria. Gestational diabetes, mechanical ventilator
      support (MV) and PVD at 7 days were associated with LRD. The combination of PVD
      and MV support at 7 days was among the strongest predictors of LRD (OR: 8.1; CI:
      3.1 - 21.9, p<0.001). Modeled prenatal and early postnatal factors accurately
      predicted LRD (AUC 0.764). Adding BPD status at 36 weeks PMA to the model did not
      change the accuracy (AUC 0.771). CONCLUSIONS: Early echocardiographic evidence of
      PVD after preterm birth in combination with other perinatal factors is a strong
      risk factor for LRD, suggesting that early PVD may contribute to the pathobiology
      of BPD.

PMID- 30303396
TI  - Olive mill wastewaters: quantitation of the phenolic content and profiling of
      elenolic acid derivatives using HPLC-DAD and HPLC/MS2 with an embedded polar
      group stationary phase.
AB  - Olive mill wastewaters (OMWs) are important by-products of olive oil production.
      The wide availability and the forbidding economic costs of OMWs disposal have
      generated interest in their possible exploitation as a sustainable source of
      polyphenols. The development and optimisation of improved analytical methods for
      the detailed characterisation of polyphenol molecular profiles after production
      and during storage conditions are thus required. A new analytical method based on
      reverse-phase HPLC separation of polyphenols in OMWs on an embedded-polar group
      (EPG) stationary phase is proposed as an alternative to conventional C18 columns.
      The procedure was used for the quantitation of 11 polyphenols, using diode-array
      detection (DAD), and achieving quantitation limits equal to or lower than 0.1 ug
      g-1. The same chromatographic set-up, coupled with high resolution tandem mass
      spectrometry (HPLC/ESI-Q-ToF), allowed us to identify hydroxytyrosyl esters of
      elenolic acid, whose relative abundance is proposed for monitoring the ageing of
      OMWs during storage.

PMID- 30303397
TI  - Social communication assessment after TBI: a narrative review of innovations in
      pragmatic and discourse assessment methods.
AB  - BACKGROUND: Social communication assessment after traumatic brain injury (TBI)
      remains a challenging area within speech-language pathology (SLP) clinical
      practice. Difficulties include the lack of TBI-specific standardized assessment
      instruments and limited knowledge and uptake of discourse assessment methods
      clinically. The aim of this paper was to review recent research literature
      reporting on innovative social communication and discourse assessment measures
      and methods, to guide evidence-based SLP practice and inform future research.
      MAIN CONTRIBUTION: This review describes novel standardized and non-standardized
      assessment tools for SLP use reported in TBI research literature from the past 15
      years. Measures include published assessment batteries and pragmatic rating
      scales designed for use with adults with TBI, and novel discourse tasks and
      protocols. CONCLUSION: This paper delineates social communication assessment
      measures and discourse analyses described in research literature that may be
      practical for SLPs to use with adults with TBI. The clinical implications and
      utility of these measures are discussed. This should assist SLPs in decision
      making on social communication assessment for adults with TBI. Further research
      is needed to investigate translation of research knowledge on discourse
      assessment methods to SLP practice.

PMID- 30303398
TI  - Measuring treatment response in children with autism spectrum disorder:
      Applications of the Brief Observation of Social Communication Change to the
      Autism Diagnostic Observation Schedule.
AB  - This study aims to determine the validity and reliability of applying the coding
      strategy from the Brief Observation of Social Communication Change, a newly
      validated treatment outcome measure, to videotaped segments of the Autism
      Diagnostic Observation Schedule. Results indicate strong reliability and validity
      of the Brief Observation of Social Communication Change ratings using the Autism
      Diagnostic Observation Schedule segments in detecting changes in social
      communication over the course of treatment in young, minimally verbal children
      with autism spectrum disorder. Results also suggest that the Brief Observation of
      Social Communication Change, when applied to Autism Diagnostic Observation
      Schedule segments, may be more sensitive in detecting subtle changes in social
      communication compared to the Autism Diagnostic Observation Schedule Calibrated
      Severity Scores. These results may support the application of the Brief
      Observation of Social Communication Change to pre-existing datasets of Autism
      Diagnostic Observation Schedule videos to examine treatment responses.

PMID- 30303399
TI  - A Phenomenological Study of Italian Students' Responses to Professional Dilemmas:
      A Cross-Cultural Comparison.
AB  - : Phenomenon: Medical professionalism is a complex construct, based in social and
      cultural influences, yet little research has been done to show how culture
      influences the behaviors and attitudes of medical students. We presented Italian
      students with the same professional dilemmas used in a previous Canadian and
      Taiwanese cross-cultural study to look for similarities and differences and
      detect elements of Italian culture that influenced how students responded to
      dilemmas. The aim was to provide medical educators with some insights into
      students' behavioral strategies and feelings when faced with a professional
      dilemma. APPROACH: Using Giorgi's method, we performed a phenomenological
      analysis of 15 interviews of Italian medical students who responded to
      standardized video scenarios representing professional dilemmas. These videos
      were used in Canada and Taiwan and were translated into Italian. All students
      were from the same degree course, at Year 6, and were recruited on a voluntary
      basis at the beginning of the Internal Medicine course. Interview transcripts
      were anonymized before analysis. FINDINGS: Scenarios were perceived as realistic
      and easy to envision in Italy. Four themes emerged: establishing priority among
      principles, using tactics to escape the dilemma, defending the self, and
      defending the relationships. When compared with previous studies, we noted that
      Italian students did not mention the principles of reporting inappropriate
      behavior, seeking excellence, or following senior trainees' advice. Insights:
      This is the first cross-cultural study of professionalism that involves a
      Mediterranean country and the observed differences could be interpreted as
      expressions of Italian cultural traits: distrust toward authority and a
      cooperative rather than competitive attitude. These findings have practical
      implications for educators to design and run curricula of professionalism with
      culturally appropriate topics. They highlight the need for more cross-cultural
      research.

PMID- 30303400
TI  - Ethnic differences in out-of-hospital cardiac arrest among Middle Eastern Arabs
      and North African populations living in Qatar.
AB  - AIMS: There are very few studies comparing epidemiology and outcomes of out-of
      hospital cardiac arrest (OHCA) in different ethnic groups. Previous ethnicity
      studies have mostly determined OHCA differences between African American and
      Caucasian populations. The aim of this study was to compare epidemiology,
      clinical presentation, and outcomes of OHCA between the local Middle Eastern Gulf
      Cooperation Council (GCC) Arab and the migrant North African populations living
      in Qatar. METHODS: This was a retrospective cohort study of Middle Eastern GCC
      Arabs and migrant North African patients with presumed cardiac origin OHCA
      resuscitated by Emergency Medical Services (EMS) in Qatar, between June 2012 and
      May 2015. RESULTS: There were 285 Middle Eastern GCC Arabs and 112 North African
      OHCA patients enrolled during the study period. Compared with the local GCC
      Arabs, univariate analysis showed that the migrant North African OHCA patients
      were younger and had higher odds of initial shockable rhythm, pre-hospital
      interventions (defibrillation and amioderone), pre-hospital scene time, and
      decreased odds of risk factors (hypertension, respiratory disease, and diabetes)
      and pre-hospital response time. The survival to hospital discharge had greater
      odds for North African OHCA patients which did not persist after adjustment.
      Multivariable logistic regression showed that North Africans were associated with
      lower odds of diabetes (OR 0.48, 95% CI 0.25-0.91, p = 0.03), and higher odds of
      initial shockable rhythm (OR 2.86, 95% CI 1.30-6.33, p = 0.01) and greater scene
      time (OR 1.02 95% CI 1.0-1.04, p = 0.02). CONCLUSIONS: North African migrant OHCA
      patients were younger, had decreased risk factors and favourable OHCA rhythm and
      received greater ACLS interventions with shorter pre-hospital response times and
      longer scene times leading to better survival.

PMID- 30303401
TI  - An in-depth look into the association between morningness-eveningness and well
      being: evidence for mediating and moderating effects of personality.
AB  - Morningness-eveningness and standard personality traits are associated with well
      being but few studies have directly compared the two types of construct as
      correlates of life satisfaction. Influences on well-being common to both
      chronotype and personality may include shared biological bases for depression and
      sleep disturbance, tendencies toward social jetlag, and emotion-regulation
      mechanisms. The current study tested mediation and moderation hypotheses in a
      sample of 379 Polish adults. The first hypothesis was that conscientiousness and
      emotional stability traits would mediate the relationship between morningness and
      life satisfaction. Consistent with previous results, morningness, the two
      personality traits, and satisfaction tended to be mutually positively correlated.
      A multiple mediation analysis showed that both traits partially mediated the
      morningness-satisfaction association. Data are compatible with morningness
      influencing personality development adaptively, although other causal hypotheses
      could be advanced. The second hypothesis was that extraversion would moderate the
      association between chronotype and satisfaction. This hypothesis was supported,
      with extraverted evening types showing disproportionately high life satisfaction,
      whereas introverted evening types showed the lowest levels of satisfaction. Level
      of extraversion may influence whether or not evening types choose to engage in
      adaptive social activities that boost well-being during the evening hours.
      Results demonstrate the importance of investigating both chronotype and
      personality in studies of well-being.

PMID- 30303402
TI  - Assessing mechanisms of benefit in adult day programs: the adult day services
      process and use measures.
AB  - OBJECTIVES: A limitation of adult day service (ADS) research is that there
      remains little understanding of how these community-based long-term care programs
      operate to benefit clients or family caregivers (i.e. the process of ADS use).
      The purpose of this study was to validate the 'ADS Process and Use Measures'
      (APUM) which were developed to assess such mechanisms. METHOD: Participant
      observation and semi-structured interviews in two ADS settings resulted in
      qualitative data to inform a conceptual model, subscales, and Likert-scale items.
      Three experts in ADS research reviewed the initial 129-item version of the APUM
      to establish content validity, and 27 family caregivers of current or prior ADS
      clients provided feedback on face validity of a subsequent 58-item version.
      RESULTS: Principal components and confirmatory factor analyses on a sample of 269
      family members of ADS clients recruited from 90 programs throughout the U.S.
      established a measure featuring 5 domains, 12 reliable subscales, and 49 items.
      Analysis of discriminant and convergent validity found that various subscales
      from four of the domains (Why ADS is Used, Events Prior to Use, Why ADS Does Not
      Work, and Pathways to Benefits) were significantly associated (p < 0.05) with
      family caregiver distress and ADS client quality of life variables. CONCLUSION:
      The ADS Process and Use Measures effectively assess mechanisms of program benefit
      and could help to enhance the overall quality of these critical community-based
      long-term care options for older persons and their families.

PMID- 30303403
TI  - Keystone: Exploring Pediatric Residents' Experiences in a Longitudinal Integrated
      Block.
AB  - PROBLEM: Residency training in many specialties has traditionally been divided
      into short, discrete, single-specialty rotations. Although providing the learner
      with in-depth exposure to a specific discipline, educators have challenged this
      rotational model, citing problems with patient and team continuity and
      maladaptive coping. Longitudinal integrated clerkships, adopted by many medical
      schools, offer an alternative model and have demonstrated improved outcomes for
      students related to patient-centeredness, advocacy, and integration with teams.
      Despite this, longitudinal integrated training in residency is rare.
      INTERVENTION: We developed a novel 3-month longitudinal integrated block for
      residents, called Keystone. The block combined 3 previously discrete, shorter
      rotations in developmental-behavioral pediatrics, advocacy, and emergency
      medicine into a longer and integrated experience. Within each week, the block
      utilized half-day sessions in the resident's primary care clinic, a new
      continuity Developmental Behavioral Pediatrics clinic where the resident worked
      with the same faculty preceptor and interprofessional team each week, shifts in
      the emergency department, and half-day sessions dedicated to clinic- and
      community-based advocacy activities. CONTEXT: The context was a single, large
      pediatric urban residency program based at 2 university-affiliated hospitals, an
      academic freestanding children's hospital, and academic safety net hospital.
      OUTCOME: Using a phenomenologic framework, we conducted interviews and a focus
      group discussion to explore residents' attitudes about the block; their
      perceptions regarding the block's impact on relationships with preceptors, peers,
      or patients; and the block's impact on learning and practice. Fourteen residents
      participated, 10 in interviews and 4 in the focus group discussion. Six themes
      emerged from thematic analysis: (a) the longitudinal nature of Keystone
      influenced professional relationships and as a result entrustment, (b) the
      longitudinal integrated design shaped engagement and learning, (c) flexibility
      promoted work-life balance and self-directed learning, (d) learners experienced
      time and space for professional identity development, (e) Keystone provided a
      unique opportunity to reclaim patient-centeredness, and (f) learners experienced
      important advantages and challenges related to the schedule. LESSONS LEARNED: The
      longitudinal integrated nature of Keystone provided a novel structure for
      addressing important yet challenging educational goals in residency, including
      enhancing relationships, facilitating entrustment and engagement, encouraging
      patient-centeredness, and emphasizing the importance of self-directed learning.

PMID- 30303404
TI  - Association between ambient temperature and chronic obstructive pulmonary
      disease: a population-based study of the years of life lost.
AB  - Limited evidence on the burden of chronic obstructive pulmonary disease (COPD)
      attributable to ambient temperature. We aim to explore the association between
      ambient temperature and years of life lost (YLL), and to get a more intuitive
      understanding of the dangers of COPD in China. Death and meteorological data of
      31 Chinese provincial capital cities during 2008-2013 was analyzed in this study.
      Distributed Lag Non-linear Model (DLNM) was used to estimate the association
      between ambient temperature and mortality. The attributable fraction (AF) to cold
      effect ranged from 8.19 (95%CI: -8.52,19.38) to 28.98 (95%CI: -64.78,67.59),
      while the AF to heat effect varied from 0.02 (95%CI: -0.13,0.05) to 5.73 (95%CI:
      0.31,10.22). Cold effect was higher than heat effect on COPD in women and
      elderly, heat effect was higher in men and younger. Low temperature can cause
      more serious disease burden of COPD than high temperature.

PMID- 30303405
TI  - Oral Coadministration of an Intramuscular DNA/Modified Vaccinia Ankara Vaccine
      for Simian Immunodeficiency Virus Is Associated with Better Control of Infection
      in Orally Exposed Infant Macaques.
AB  - The majority of human immunodeficiency virus (HIV) type 1 infections in infants
      are acquired orally through breastfeeding. Toward development of a pediatric HIV
      vaccine to prevent breastmilk transmission, we tested the efficacy of a
      simultaneous oral and intramuscular (IM) vaccination regimen for preventing oral
      simian immunodeficiency virus (SIV) transmission in infant rhesus macaques. Two
      groups of neonatal macaques were immunized with DNA encoding SIV virus-like
      particles (DNA-SIV) on weeks 0 and 3, then boosted with modified vaccinia Ankara
      (MVA) virus expressing SIV antigens (MVA-SIV) on weeks 6 and 9. One group was
      prime/boosted by the IM route only. Another group was immunized with DNA by both
      the IM and topical oral (O) buccal routes, and boosted with MVA-SIV by both the
      IM and sublingual (SL) routes. A third group of control animals received saline
      by O + IM routes on weeks 0 and 3, and empty MVA by SL + IM routes on weeks 6 and
      9. On week 12, infants were orally challenged once weekly with SIVmac251 until
      infected. The vaccine regimen that included oral routes resulted in reduced peak
      viremia. The rate of infection acquisition in vaccinated infants was found to be
      associated with prechallenge intestinal immunoglobulin G (IgG) responses to SIV
      gp120 and V1V2. Peak viremia was inversely correlated with postinfection
      intestinal IgG responses to gp120, gp41, and V1V2. These results suggest that
      codelivery of a pediatric HIV vaccine by an oral route may be superior to IM-only
      regimens for generating mucosal antibodies and preventing HIV breastmilk
      transmission in neonates.

PMID- 30303406
TI  - Inducing intravesical hyperthermia of the ex-vivo porcine bladder wall:
      radiofrequency-induction versus recirculation using a custom-made device.
AB  - INTRODUCTION: Several techniques can be used to treat intravesical
      chemohyperthermia (ChHT). We compared radiofrequency-induced hyperthermia (RF-HT)
      with conductive hyperthermia (C-HT) for their ability to induce bladder wall
      temperatures of >40.5  degrees C, the target temperature for ChHT. MATERIALS AND
      METHODS: Fresh porcine bladders (n = 12) were placed in a temperature-controlled
      saline bath to simulate body temperature and circulation. HT was induced with RF
      HT (43  degrees C) or C-HT (inflow temperature 44 and 46  degrees C) using a
      custom-made device. In two additional bladders, we varied intravesical solution
      and volume. Temperatures were recorded with a three-way catheter containing three
      mucosal and two urethral thermocouples (TCs) and a 915 MHz RF antenna, and with
      external TCs in the bladder wall at three different levels and three different
      locations. RESULTS: Target temperature (40.5  degrees C) was reached in the
      submucosa at all locations by both techniques. In the detrusor, target
      temperature was reached by RF-HT at the bladder neck and side wall. C-HT46
      reached significantly higher submucosal temperatures at the side wall. The
      bladder dome seemed best heated by C-HT, although a high inflow temperature (46
      vs. 44  degrees C) was required (ns). Intravesical saline resulted in higher
      temperatures than sterile water for RF-HT. A volume of 100 mL resulted in higher
      bladder dome temperatures for RF-HT, and higher bladder neck with lower dome
      temperatures for C-HT. CONCLUSION: Our results indicate a slightly superior
      heating capacity for RF-HT compared to C-HT, whereas for the bladder dome, the
      reverse seems true. Comparative studies are warranted to evaluate whether HT
      efficacy differs between both techniques, with emphasis on tumor location.

PMID- 30303407
TI  - Tolmetin sodium-loaded thermosensitive mucoadhesive liquid suppositories for
      rectal delivery; strategy to overcome oral delivery drawbacks.
AB  - Tolmetin sodium (TS) is a nonsteroidal anti-inflammatory drug (NSAID) indicated
      for treatment of musculoskeletal issues. As other NSAID, TS displays a marked
      side effects on the gastro-intestinal (GI) tract after oral administration.
      Traditional solid suppositories can cause pain and discomfort for patients, may
      reach the end of the colon; consequently, the drug can undergo the first-pass
      effect. TS liquid suppository (TS-LS) was developed to enhance patient compliance
      and rectal mucosal safety in high-risk patients receiving highly NSAID therapy.
      This work was conducted to optimize and evaluate Poloxamer P407/P188-based
      thermoresponsive TS-LS by using mucoadhesive polymers such as methylcellulose
      (MC). TS-LS was prepared by cold method and characterized their in vitro
      physicochemical properties as gelation temperature (GT), gel strength,
      bioadhesive properties, and in vitro release. The safety of the prepared
      suppository on rectum, stomach, and liver was evaluated histologically.
      Pharmacokinetic analyses were performed to compare rectal TS-LS to orally
      Rhumtol(r) capsules. The results showed that the optimized TS-LS; composed of
      P407/P188/MC (21/9/0.5% w/w) displayed gelation at rectum temperature ~32.90 
      degrees C, gel strength of 21.35 s and rectal retention force at the
      administration site of 24.25 * 102 dyne/cm2. Moreover, TS-LS did not cause any
      morphological damage to the rectal tissues. Pharmacokinetic parameters of
      optimized TS-LS formulation revealed 4.6 fold increase in bioavailability as
      compared to Rhumtol(r) capsules. Taken together, the results demonstrated that
      liquid suppository is a potential and physically safe rectal delivery carrier for
      improvement rectal bioavailability and in vivo safety of TS.

PMID- 30303408
TI  - Development and Preliminary Validation of the Lung Transplant Quality of Life (LT
      QOL) Survey.
AB  - INTRODUCTION: Although lung transplantation aims to improve health-related
      quality of life (HRQL), existing instruments fail to include health domains
      considered important in this population. We aimed to develop a comprehensive lung
      transplant-specific instrument to address this shortcoming. METHODS: We developed
      a pool of 126 candidate items addressing domains previously identified as
      important by lung transplant recipients. Through cognitive interviews conducted
      in 43 transplant recipients, items deemed irrelevant or redundant were dropped.
      The 84 remaining items were field tested in lung transplant recipients.
      Exploratory and confirmatory factor analyses (CFA) were used to evaluate the
      factor structure and scales were evaluated for internal consistency and construct
      validity. RESULTS: The 84-item preliminary survey was administered to 201 lung
      transplant recipients with a mean age of 57.9 +/-12.7 years; 46% were female.
      After factor analyses and internal consistency evaluation, we retained 60 items
      comprising the Lung Transplant Quality of Life (LT-QOL) Survey. The LT-QOL
      contains ten scales that measure symptoms, health perceptions, functioning, and
      well-being. The CFA model had good approximate fit (comparative fit index =0.990;
      standardized root-mean-square residual =0.062). Cronbach alphas for the ten
      scales ranged from 0.75 to 0.95. Inter-scale correlations were consistent with
      hypothesized relationships. Subjects with severe chronic lung allograft
      dysfunction (CLAD; n=13) reported significantly worse HRQL than subjects without
      CLAD (n=168) on six of the ten LT-QOL scales. CONCLUSION: The LT-QOL is a new
      multidimensional instrument that characterizes and quantifies health-related
      quality of life in lung transplant recipients.

PMID- 30303409
TI  - Risk of high blood pressure associated with objective insomnia and self-reported
      insomnia complaints in major depression: A study on 703 individuals.
AB  - BACKGROUND: Since few studies have investigated the risk of high blood pressure
      associated with objective insomnia and self-reported insomnia complaints in major
      depression, the aim of this study was to examine this risk in a large sample of
      individuals with major depression. METHODS: Data from 703 individuals with major
      depression recruited from the research database of the sleep laboratory of the
      Erasme Hospital were analysed. High blood pressure status was defined by the
      presence of one of the following: self-reports at interview of either a physician
      diagnosis or taking antihypertensive medication; or an average systolic blood
      pressure >=140 mmHg or an average diastolic blood pressure >=90 mmHg during at
      least two medical examinations. Logistic regression analyses were conducted to
      examine the risk of high blood pressure associated with objective insomnia and
      self-reported insomnia complaints in major depression. RESULTS: After adjustment
      for major confounding factors associated with high blood pressure, multivariate
      logistic regression analysis revealed that severe objective insomnia, low
      complaints of repeated nighttime awakenings or early morning awakening, and
      intermediate or low self-reported insomnia complaints were significant risk
      factors of high blood pressure in major depression. CONCLUSION: In major
      depression, severe objective insomnia and lower self-reported insomnia complaints
      are associated with higher risk of high blood pressure, which justifies a better
      management of objective insomnia and a better assessment of insomnia complaints
      in this particular subpopulation to avoid the negative consequences related to
      the co-occurrence of high blood pressure and major depression. ABBREVIATIONS:
      AHI, Apnea-Hypopnea Index; BDI, Beck Depression Inventory; BMI, Body Mass Index;
      DSM IV-TR, Diagnostic and Statistical Manual of Mental Disorders fourth edition -
      Text Revision; ESS, Epworth Sleepiness scale; ISI, Insomnia Severity Index; HBP,
      High Blood Pressure; OSA, Obstructive Sleep Apnea Syndrome; REM, rapid eye
      movement sleep.

PMID- 30303411
TI  - Learning (by) osmosis: an approach to teaching osmolarity and tonicity.
AB  - Understanding osmolarity and tonicity is one of the more challenging endeavors
      undertaken by students of the natural sciences. We asked students who completed a
      course in animal physiology to submit an essay explaining what they found most
      perplexing about this subject, and what in-class activities proved most useful to
      them. Students had difficulty distinguishing osmolarity from tonicity and
      determining tonicity based on the solution's composition. The most useful
      activities were questions requiring simultaneous consideration of both osmolarity
      and tonicity. Problems that require calculating osmotic concentration and the
      volumes of body fluid compartments after administration or loss of various
      solutions emphasize the significance of osmolarity and tonicity in the context of
      systemic homeostasis and clinical medicine. We hope that our approach to teaching
      osmolarity and tonicity will prove useful to physiology lecturers who are looking
      for new ways of introducing this complicated topic to their health professions
      students.

PMID- 30303410
TI  - An analysis of the survival impact of dexmedetomidine in children undergoing
      cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.
AB  - OBJECTIVE: Recent evidence suggests the alpha2-adrenoreceptor agonist
      dexmedetomidine may promote metastasis of cancer cells. In this study we sought
      to evaluate the impact of dexmedetomidine administration on the survival of
      children and adolescents with cancer. DESIGN: Retrospective chart review.
      SETTING: Comprehensive cancer center. PATIENTS: Children and adolescents who had
      undergone cytoreductive surgery with hyperthermic intraperitoneal chemotherapy
      for peritoneal carcinomatosis. INTERVENTION: Intraoperative and/or early
      postoperative (within 24 hours of surgery) administration of dexmedetomidine.
      MEASUREMENTS: Multivariable cox proportional hazard models were used to assess
      the association between dexmedetomidine administration and progression free
      survival (PFS) or overall survival (OS). MAIN RESULTS: Ninety-three patients were
      identified. The median age was 12 years, 42% were female, and 35% received
      dexmedetomidine. There were no significant differences between the baseline and
      perioperative characteristics of patients who received dexmedetomidine and those
      who did not. In the multivariable analysis, the administration of dexmedetomidine
      was not associated with PFS (HR = 1.20, 95% CI [0.60-2.41], p = .606) or OS (HR =
      0.81, 95% CI [0.35-1.85], p = .611). CONCLUSION: In this retrospective study of
      children and adolescents who had undergone a major oncologic surgery, the
      intraoperative and/or early postoperative administration of dexmedetomidine was
      not associated with survival.

PMID- 30303412
TI  - Impact of an early clinical exposure project conducted by senior clinical
      students compared between participating and nonparticipating students.
AB  - An early clinical exposure project conducted by clinical students aimed to
      promote direct clinical experience to preclinical students. The aim of this study
      was to determine the effects of the project on academic achievement and study
      attitudes and habits between participating and nonparticipating students before (
      test 1) and after the project ( test 2) in the second preclinical year and at the
      end of the first semester of the first clinical year ( test 3), with a subgroup
      analysis of the first (lowest) to third (highest) tertile of the score.
      Questionnaires were sent to the first clinical year students at test 3 and asked
      the information retrospectively at test 1 and test 2 in second year preclinical
      and currently at test 3, with 83.86% (265/316) being returned. Mean percentile of
      scores was higher at test 2 compared with test 1 in the first tertile group of
      participating students. Motivation to study medicine (motivation), realization of
      application of preclinical knowledge to clinical study (application),
      understanding of clinical environment (environment), and lesson review after
      class (review) were higher for participating than nonparticipating students at
      test 2 and/or test 3. Searching additional study information was higher at test 2
      compared with test 1 only for participating students. This project could
      effectively promote application, motivation, environment, and review for
      participating vs. nonparticipating students at test 2 and/or test 3. Effortless,
      intimate, and effective communication between clinical and preclinical students
      and a direct experience in early clinical exposure might be key success factors.

PMID- 30303413
TI  - Formative online quiz on hemotherapy from blood physiology to transfusion
      medicine: a pilot study conducted with Brazilian medical students.

PMID- 30303414
TI  - Student engagement in a Human Anatomy and Physiology course: a New Zealand
      perspective.
AB  - The population diversity of New Zealand is due to the unique fusion of indigenous
      peoples of Polynesian origin (Maori), western European colonization (Pakeha), and
      more recent (20th century) immigration from the Pacific region (Pasifika).
      However, disparities in tertiary education indicate that Maori and Pasifika
      students are more likely to drop out during their first year of study and are
      less likely to complete their qualification than their Pakeha peers. Higher
      levels of course engagement may increase first-year grades, elevate academic
      performance, and encourage persistence between the first and second years of
      study. Therefore, a Student Course Engagement Questionnaire was used to quantify
      engagement in a compulsory first-year undergraduate Human Anatomy and Physiology
      course in a New Zealand university. A data mining technique was used to assign
      students into a low-engagement/low-achievement cluster, and a high
      engagement/high-achievement cluster. The skills, emotional, and participation
      interaction components of engagement were lower in Pasifika students: these
      students' academic grade was lower than those of both Maori and Pakeha students.
      The strongest predictors of cluster membership were skills engagement and
      emotional engagement, suggesting that these components outweighed other aspects
      of course engagement. Maori and Pasifika students were overrepresented in the low
      engagement/low-achievement cluster, and underrepresented in the high
      engagement/high-achievement cluster. We suggest that embedding study skills
      within course delivery, and constantly emphasizing their importance, would likely
      increase student course engagement. Also, we report that both Maori and Pasifika
      students remain more disengaged than their Pakeha peers.

PMID- 30303415
TI  - The effect of air pockets in the urinary bladder on the temperature distribution
      during loco-regional hyperthermia treatment of bladder cancer patients.
AB  - PURPOSE: Loco-regional hyperthermia combined with mitomycin C is used for
      treatment of nonmuscle invasive bladder cancer (NMIBC). Air pockets may be
      present in the bladder during treatment. The aim of this study is to quantify the
      effect of air pockets on the thermal dose of the bladder. METHODS: We analysed 16
      patients treated for NMIBC. Loco-regional hyperthermia was performed with the in
      house developed 70 MHz AMC-4 hyperthermia device. We simulated treatments with
      the clinically applied device settings using Plan2Heat (developed in-house)
      including the air pockets delineated on CT scans made following treatment, and
      with the same volume filled with urine. Temperature distributions simulated with
      and without air pockets were compared. RESULTS: The average air and fluid volumes
      in the bladder were 6.0 ml (range 0.8 - 19.3 ml) and 183 ml (range 47-322 ml),
      respectively. The effect of these air pockets varied strongly between patients.
      Averaged over all patients, the median bladder wall temperature (T50) remained
      unchanged when an air pocket was present. Temperature changes exceeded +/-0.2 
      degrees C in, on average, 23% of the bladder wall volume (range 1.3-59%), in 6.0%
      (range 0.6-20%) changes exceeded +/-0.5  degrees C and in 3.2% (range 0.0-7.4%)
      changes exceeded +/-1.0  degrees C. There was no correlation between the
      differences in temperature and the air pocket or bladder volume. There was a
      positive correlation between air pocket surface and temperature heterogeneity.
      CONCLUSION: Presence of air causes more heterogeneous bladder wall temperatures
      and lower T90, particularly for larger air pockets. The size of air pockets must
      therefore be minimized during bladder hyperthermia treatments.

PMID- 30303416
TI  - Differences in serum IL-6 response after 1  degrees C rise in core body
      temperature in individuals with spinal cord injury and cervical spinal cord
      injury during local heat stress.
AB  - OBJECTIVES: Passive rise in core body temperature achieved by head-out hot water
      immersion (HHWI) results in acute increases in serum interleukin (IL)-6 but no
      change in plasma adrenaline in patients with cervical spinal cord injury (CSCI).
      The purpose of the present study was to determine the mechanism of heat stress
      induced increase in serum IL-6. SETTING: A cross-sectional study. METHODS: The
      study subjects were nine with CSCI, ten with thoracic and lumbar spinal cord
      injury (TLSCI) and eight able-bodied (AB) subjects. Time since injury was 16.1 +/
      3.4 years in TLSCI and 16.4 +/- 4.1 years in CSCI. Subjects were subjected to
      lower-body heat stress (LBH) by wearing a hot water-perfused suit until 1 
      degrees C increase in core temperature. The levels of serum IL-6, plasma
      adrenaline, tumour necrosis factor (TNF)-alpha, C-reactive protein (CRP), and
      counts of blood cells were measured at normothermia and after LBH. RESULTS: Serum
      IL-6 concentrations increased significantly immediately after LBH in all the
      three groups. DeltaIL-6% was lower in CSCI subjects compared with AB subjects.
      Plasma adrenaline concentrations significantly increased after LBH in AB and
      TLSCI subjects, but did not change throughout the study in CSCI subjects. Cardiac
      output and heart rate increased at the end of LBH in all three groups.
      CONCLUSIONS: Under a similar increase in core temperature, DeltaIL-6% was lower
      in the CSCI group compared with the AB group. These findings suggest that the
      observed rise in IL-6 during hyperthermia is mediated, at least in part, by
      plasma adrenaline.

PMID- 30303417
TI  - Psychometric validation of team experiences questionnaire in preregistration
      Chinese health and social care students in Hong Kong.
AB  - The complexity of patients' healthcare needs can be addressed more adequately by
      professionals working as a healthcare team. In view of this, it is important to
      prepare students for collaborative work when they become professionals through a
      students' team training at the preregistration level. As intervention programs
      are implemented to promote students' collaboration, instruments like Team
      Experiences Questionnaire (TEQ) are needed. In this connection, this study which
      involved 335 Chinese students enrolled in eight health and social care programs
      from two universities in Hong Kong investigated the factor structures of the TEQ
      using construct validation approach. Using confirmatory factor analysis, we
      examined the fit of three competing models: unidimensional model, first-order
      correlated model, and second-order hierarchical model. The results demonstrated
      that the second-order hierarchical model obtained the best fit, with a higher
      order construct called total team experiences subsuming the following first order
      factors: overall satisfaction with team experiences, team impact on quality of
      learning, satisfaction with team evaluation, team impact on clinical reasoning
      ability, and professional development. The "total team experience" construct
      explained from 21.1% to 35.7% of the variance in predicting students' future
      perception of team competency and autonomy, perceived need for cooperation, and
      perception of actual cooperation. Results support the applicability of the TEQ
      second-order hierarchical model. Implications are discussed.

PMID- 30303418
TI  - Process design and optimization of bioethanol production from cassava bagasse
      using statistical design and genetic algorithm.
AB  - Bioethanol production from agro-industrial residues is gaining attention because
      of the limited production of starch grains and sugarcane, and food-fuel conflict.
      The aim of the present study is to maximize the bioethanol production using
      cassava bagasse as a feedstock. Enzymatic liquefaction, by alpha-amylase,
      followed by simultaneous saccharification and fermentation (SSF), using
      glucoamylase and Zymomonas mobilis MTCC 2427, was investigated for bioethanol
      production from cassava bagasse. The factors influencing ethanol production
      process were identified and screened for significant factors using Plackett
      Burman design. The significant factors (cassava bagasse concentration (10-50
      g/L), concentration of alpha-amylase (5-25% (v/v), and temperature of
      fermentation (27-37  degrees C)) were optimized by employing Box-Behnken design
      and genetic algorithm. The maximum ethanol concentrations of 25.594 g/L and
      25.910 g/L were obtained from Box-Behnken design and genetic algorithm,
      respectively, under optimum conditions. Thus, the study provides valuable
      insights in utilizing the cost-effective industrial residue, cassava bagasse, for
      the bioethanol production.

PMID- 30303419
TI  - Comparison of effectiveness of epidural analgesia and monitored anesthesia care
      for high-intensity focused ultrasound treatment of adenomyosis.
AB  - BACKGROUND: High-intensity focused ultrasound (HIFU) is a noninvasive
      thermodestructive procedure targeting internal organs with concentrated
      sonification energy that may cause pain. We aimed to compare the effectiveness of
      epidural analgesia (EA) and monitored anesthesia care (MAC) in HIFU treatment of
      uterine adenomyosis. MATERIALS AND METHODS: Sixty-eight patients were included in
      this case-control study. Thirty-seven patients underwent MAC; 31 patients
      underwent fluoroscope-guided epidural analgesia. The primary outcome was a
      frequency of patients reporting severe or very severe intraoperative pain.
      Secondary outcomes were differences in dosages of analgesics, ablation ratio, and
      other clinical factors. RESULTS: The EA group reported a significantly lower
      frequency of severe or very severe intraoperative pain than did the MAC group
      (41.9% vs. 75.7%; p = .006). Consumption of remifentanil during treatment was
      significantly lower in the EA group (173 +/- 189 ug vs. 426 +/- 380 ug; p =
      .001), as was the use of fentanyl in the recovery room (52 +/- 38 ug vs. 75 +/-
      44 ug; p = .030). Multivariable analysis revealed EA to be the largest
      contributing factor to increased nonperfused volume ratio (B = 0.41; 95%
      confidence interval = 0.29 to 0.53; p < .001). The frequency of thermal injury
      after HIFU was significantly lower in the EA group (22.6% vs. 54.1%; p = .008).
      CONCLUSIONS: EA during HIFU treatment of uterine adenomyosis improved quality of
      pain control and ablation ratio over MAC without increasing risk of treatment
      related complications. EA also reduced consumption of opioid analgesics during
      and after HIFU treatment.

PMID- 30303420
TI  - Compliance and persistence with Alzheimer's disease treatment: a retrospective
      analysis of multiregional hospital databases in Thailand.
AB  - AIMS: Due to the lack of studies evaluating compliance or persistence with
      Alzheimer's Disease (AD) treatment outside High-Income Countries (HICs), this
      study aimed to assess compliance, persistence, and factors associated with non
      compliance and non-persistence by utilizing existing "real-world" information
      from multiregional hospital databases in Thailand. MATERIALS AND METHODS: Study
      subjects were retrospectively identified from databases of five hospitals located
      in different regions across Thailand. AD patients aged >=60 years who were newly
      prescribed with donepezil, galantamine, rivastigmine, or memantine between 2013
      and 2017 were eligible for analysis. The Medication Possession Ratio (MPR) was
      used as a proxy for compliance, while the Kaplan-Meier survival analysis was
      employed to estimate persistence. Logistic and Cox regressions were used to
      assess determinants of non-compliance and non-persistence, adjusted for age and
      gender. RESULTS: Among 698 eligible patients, mean (SD) MPR was 0.83 (0.25), with
      70.3% of the patients compliant to the treatment (having MPR >= 0.80). Half of
      the patients discontinued their treatment (having a treatment gap >30 days)
      within 177 days with a 1-year persistence probability of 21.1%. The patients
      treated in the university-affiliated hospital were more likely to be both non
      compliant (OR = 1.71; 95% CI = 1.21-2.42) and non-persistent (HR = 1.33; 95% CI =
      1.12-1.58). In addition, non-compliance was higher for those prescribed with
      single AD treatment (OR = 2.52; 95% CI = 1.35-4.69), while non-persistence was
      higher for those unable to reimburse for AD treatment (HR = 1.34; 95% CI = 1.11
      1.62). LIMITATIONS: By using retrospective databases, a difficulty in validating
      whether the medications are actually taken after being refilled may over-estimate
      the levels of compliance and persistence. Meanwhile, possible random coding
      errors may under-estimate the strength of association findings. CONCLUSIONS: This
      study reveals the situation of compliance and persistence on AD treatment for the
      first time outside HICs. The determinants of non-compliance and non-persistence
      underline key areas for improvement.

PMID- 30303421
TI  - Whole body heat exposure modulates acute glucose metabolism.
AB  - AIM: Exercise modulates glucose tolerance and homeostasis in both healthy and
      diabetic individuals. Heat stress is a fundamental element of exercise. The acute
      glycemic response and alterations in glucose clearance following whole body
      passive heat stress in the absence of muscle activity has yet to be examined in
      humans. Knowledge of this relationship may prove useful, particularly in
      populations with compromised glucoregulation from reduced activity. PURPOSE: To
      determine insulin/glucose levels before and after an acute bout of heat stress in
      healthy, lean individuals and examine the effects of whole body heat stress
      (WBHS) and exercise on acute glucose tolerance in an expanded cohort. METHODS:
      Ten subjects (24.1 +/- 0.7 years) participated in a randomized control/WBHS
      session (up to 30 minutes at 73  degrees C) with fasting glucose (FG) and insulin
      drawn at baseline, immediately after and 30 minutes post heat stress. In the
      follow-up experiment, 20 anthropometrically diverse subjects (24.6 +/- 2.1 years)
      underwent an oral glucose tolerance test (OGTT) under the conditions above.
      RESULTS: FG levels rose 10% immediately following heat stress (8.6 (+/-5.6)
      mg/dl, p < .01) and returned to near baseline levels 30 minutes following WBHS.
      Insulin release showed its greatest increase at 30 minutes post WBHS (2.7 +/-
      3.5) uU/ml p < .05). WBHS resulted in a decrease in glucose uptake [AUC increased
      8.2% (1430.6 +/- 1957.03) mg/dl (p = .005)], particularly in nonlean individuals.
      CONCLUSION: WBHS modulates physiologic markers of metabolism. An acute bout of
      WBHS increases glucose and insulin levels in healthy individual and decreases
      glucose uptake in response to a glucose challenge, particularly those who are non
      lean.

PMID- 30303422
TI  - A look inside the Atwood lab.

PMID- 30303423
TI  - Incidence and Risk Factors for Post-Intravitreal Injection Endophthalmitis in a
      Modified Operating Room Setting.
AB  - PURPOSE: To evaluate the incidence and risk factors of post-intravitreal
      injection (IVI) endophthalmitis in a single center modified operating room (OR)
      setting. METHODS: In a retrospective chart review study, patients who underwent
      IVI in a modified OR between September 2014 and November 2016 were included.
      Cases of post-IVI endophthalmitis were identified from the Hospital Infection
      Control Committee records, which tracks all post-procedure infections. RESULTS:
      51 472 IVIs (37 814 patients) including 13 658 bilateral simultaneous injections
      were performed during the study period. There were 17 cases of endophthalmitis
      (0.033%, 95% CI 0.019%-0.052%). There were no cases of bilateral endophthalmitis.
      Age, sex, indication for IVI, simultaneous bilateral injections, number of
      previous injections, and type of injected drug were not significantly associated
      with incidence of endophthalmitis. CONCLUSION: Post-IVI endophthalmitis is rare
      in this modified OR setting. Simultaneous bilateral IVIs and on-site preparation
      of injections are safe under these conditions.

PMID- 30303424
TI  - Molecular mechanisms that change synapse number.
AB  - Synapses are the functional units of the nervous system, and their number and
      protein composition undergo changes over a wide time scale. These synaptic
      changes manifest into differential behavioural outputs and, in turn, changes in
      the external conditions to the individual may elicit changes in synapses. We
      review here publications appeared during the last 10 years in which advances on
      molecular and cellular mechanisms for synapse changes have been reported. We
      focus on synaptic changes occurring in the time range of minutes to hours,
      mainly.

PMID- 30303425
TI  - Feasibility of targeting canine soft tissue sarcoma with MR-guided high-intensity
      focused ultrasound.
AB  - PURPOSE: Magnetic resonance imaging-guided high-intensity-focused ultrasound (MR
      HIFU) is a non-invasive treatment modality that precisely focuses ultrasound
      energy within a tumour and can be customised to result in a wide range of local
      bioeffects. The purpose of this study was to determine the feasibility of using
      MR-HIFU to treat soft tissue sarcoma (STS) in dogs. MATERIALS AND METHODS:
      Medical records of dogs admitted to the Virginia-Maryland College of Veterinary
      Medicine from 1 January 2012 to 31 December 2016 were searched for a diagnosis of
      sarcoma with available cross-sectional imaging of the tumour (MRI or CT). Fifty
      three (53) dogs were eligible for inclusion. Tumor tissue (in bone as well as in
      soft tissue) was considered targetable unless: (1) the ultrasound path was
      completely obstructed by bone or gas and (2) the MR-HIFU target was within the
      spinal cord or less than 1 cm from the margin of the spinal cord. Tumors were
      categorised as <50% targetable, >=50% targetable or non-targetable. RESULTS:
      Eighty-one percent of STS (81.1%, 43/53) were targetable. The head/spine tumour
      sites had the highest proportion of non-targetable tumours (36%, 9/25). The
      majority of truncal and axillary tumours were >=50% targetable (88.9%, 16/18)
      ,and all extremity tumours were considered >=50% targetable (100%, 5/5).
      CONCLUSIONS: The majority of STS were targetable. This is the first study to
      evaluate MR-HIFU targetability of canine STS. HIFU has potential as a therapeutic
      modality for treating STS in dogs, and this veterinary application is a possible
      model for treatment of naturally occurring STS in humans.

PMID- 30303426
TI  - Supporting health system transformation through an interprofessional education
      experience focused on population health.
AB  - The purpose of the study was to determine the impact of an interprofessional
      education (IPE) experience on first year students across all schools of a health
      sciences center on the topic of pediatric immunizations. The authors conducted a
      pre-/post-test at Louisiana State University Health Sciences Center-New Orleans
      with 731 first year students from 25 academic programs encompassing all six
      schools (Allied Health, Dentistry, Graduate Studies, Medicine, Nursing and Public
      Health). In the four questions related to the Interprofessional Education
      Collaborative (IPEC) sub-competencies and the three questions related to
      professional role regarding immunizations, there was a statistically significant
      difference in the pre-/post-test survey results (P < 0.0001). Student learning
      related to the collaboration needed to make a larger impact on patient outcomes
      was demonstrated through assessment of an open-ended question. IPE experiences
      can improve first-year students' perceptions of IPEC sub-competencies regarding
      the importance of population health and teamwork. By utilizing a population
      health focus with IPE activities, novice learners are equipped to learn and apply
      collaborative practice skills along with recognizing the importance of promoting
      overall health and well-being instead of just health care.

PMID- 30303427
TI  - A Prospective, Single-Blind, Randomized, Phase III Study to Evaluate the Safety
      and Efficacy of Fibrin Sealant Grifols as an Adjunct to Hemostasis During Soft
      Tissue Open Surgery.
AB  - BACKGROUND/PURPOSE: Rapid hemostasis, an essential prerequisite of good surgical
      practice during surgical bleeding, including soft tissue open surgery, often
      requires adjunctive treatment. We evaluated the safety and hemostatic
      effectiveness of a human plasma-derived fibrin sealant (FS Grifols) in soft
      tissue open surgery. METHODS: Patients with moderate soft tissue bleeding during
      open, urologic, gynecologic or general surgery were studied. The trial consisted
      of a preliminary phase (to familiarize investigators with the technique for FS
      Grifols application and the intraoperative procedures required by the clinical
      protocol) and a primary phase: in both phases, patients were randomized 1:1 to FS
      Grifols or Surgicel(r). The primary efficacy endpoint, based on analysis of
      subjects in the primary phase of the study, was to evaluate whether FS Grifols
      was non-inferior to Surgicel(r) in achieving hemostasis, based on the proportion
      of subjects in both treatment groups who achieved hemostasis at the target
      bleeding site (TBS) by 4 min (T4) following the start of treatment application.
      Safety assessments included adverse events (AEs), vital signs, physical
      assessments, common clinical laboratory tests, viral markers, and immunogenicity.
      RESULTS: A total of 224 subjects were randomized (primary phase): FS Grifols (N =
      116), Surgicel(r) (N = 108). The 95% CI at T4 for the ratio of the proportion of
      patients achieving hemostasis in the two treatment groups was 1.064 (0.934,
      1.213), indicating non-inferiority for FS Grifols vs. Surgicel(r). The rate of
      hemostasis at the TBS by T4 in both phases of the study was higher in the FS
      Grifols treatment group (preliminary phase: 90.2%; primary phase: 82.8%) than in
      the Surgicel(r) treatment group (preliminary phase: 78.8%; primary phase: 77.8%).
      Overall, reported AEs were as expected in surgical patients and were similar
      between the two treatment groups. CONCLUSIONS: This study shows the non
      inferiority in time to hemostasis of FS Grifols vs. Surgicel as an adjunct to
      hemostasis in patients undergoing soft tissue open surgery, and a similar rate of
      AEs.

PMID- 30303428
TI  - Parents as partners: investigating the role(s) of mothers in coordinating health
      and education activities for children with chronic care needs.
AB  - Interprofessional collaboration (IPC) between health professionals, and educators
      is an essential component of academic success and well-being for children who
      experience chronic illnesses. This study sought to understand parents' roles in
      and perceptions of IPC between their child's healthcare professionals and
      educators. We recruited 23 mothers to participate in our study. Data were
      analyzed using a combination of univariate analyses and content analysis.
      Overall, parents reported that they could effectively communicate their child's
      health and educational needs with health and educational professionals, but
      statistical analysis determined moderately increased challenges presenting
      information across professions. Most participants (n = 19) indicated that IPC
      between health and educational professionals could be improved. Effectively
      engaging parents as partners in IPC can promote more seamless collaboration and
      communication of a child's needs and offer a greater likelihood of achieving a
      child's health and educational goals.

PMID- 30303429
TI  - Vaccine coverage in PLWH: disparities and potential impact of vaccine hesitancy.

PMID- 30303430
TI  - Vergence Profile and Prevalance of Non-Strabismic Vergence Anomalies Among School
      Children in Abia State, Nigeria.
AB  - PURPOSE: To determine the prevalence of non-strabismic vergence anomalies and
      their relationship with age, gender, and school level in children aged 10-16
      years Method: A cross-sectional study was conducted among 537 children (255 male,
      282 females; mean age 13.0 +/- 2.0, years) selected from nine schools using
      stratified, cluster, and random sampling. The participants completed a
      Convergence Insufficiency Symptom Survey (CISS) and eye examinations, including
      the measurement of visual acuity, non-cycloplegic refraction, cover test, near
      point of convergence, fusional vergences, accommodative functions, and ocular
      health evaluation. All binocular tests were performed following the subjective
      refraction with the corrective lenses in place, if prescribed. RESULTS: The
      prevalence of low suspect, high suspect, and definite convergence insufficiency
      was 9.6%, 5.8%, and 4.1%, respectively. Other prevalence estimates included
      convergence excess (2.9%), fusional vergence dysfunction (2.6%), basic exophoria
      (1.7%), basic esophoria (2.8%), divergence insufficiency (0.8%), and divergence
      excess (0.6%). The prevalence of high suspect (p < 0.01) and definite (p < 0.01)
      convergence insufficiency was significantly higher in older than younger
      children, and as expected, in secondary more so than primary school children (p =
      0.01). There was no statically significant association between gender and various
      vergence anomalies. CONCLUSION: The study showed that vergence anomalies are
      common vision conditions among Abia State school children. Given the importance
      of visual skills in learning and academic achievements, there is a need to
      develop screening and management strategies that will target those visual
      conditions to prevent educational and social progress being affected.

PMID- 30303431
TI  - A three-dimensional transient computational study of 532-nm laser thermal
      ablation in a geometrical model representing prostate tissue.
AB  - OBJECTIVE: Laser with 532-nm wavelength (GreenLightTM) is clinically approved to
      treat benign prostatic hyperplasia (BPH). However, low rate of tissue ablation
      and excessive thermal coagulation are shortcomings of this therapy. The goal of
      this study was to use a mathematical model to identify clinically viable laser
      settings that have the potential to improve treatment time and outcomes. METHODS:
      A three-dimensional transient computational model was developed, validated
      against analytical and experimental results, and utilized to investigate the
      response of tissues subjected to continuous-wave and pulsed lasers emitting 532
      nm light (GreenLightTM laser). The impact of laser power (10-125 W), pulse
      duration (100 ns and 100 us) and pulse frequency (10 and 100 Hz) on tissue
      ablation and coagulation rates and sizes was explored. RESULTS: Good agreement
      between the computational model and analytical and experimental results was
      found. Continuous-wave laser results in 13% less coagulation zone thickness and
      10% higher ablation rate than the low frequency pulsed laser. With increasing
      laser power; ablation rate is expected to increase linearly, while coagulation
      zone thickness is expected to increase asymptotically. Pulse frequency influence
      on tissue ablation and coagulation is relevant at high power, but pulse duration
      is found to have minimal effect at all powers. CONCLUSIONS: Laser thermal tissue
      ablation employing continuous wave mode lasers outperforms that employing pulsed
      mode lasers. Laser power settings should be carefully selected to maximize the
      rate of tissue ablation and minimize tissue coagulation.

PMID- 30303433
TI  - Multivariate analysis as a method to understand variability in a complex
      excipient, and its contribution to formulation performance.
AB  - A key part of the Risk Assessment of excipients is to understand how raw material
      variability could (or does) contribute to differences in performance of the drug
      product. Here we demonstrate an approach which achieves the necessary
      understanding for a complex, functional, excipient. Multivariate analysis (MVA)
      of the certificates of analysis of an ethylcellulose aqueous dispersion
      (Surelease) formulation revealed low overall variability of the properties of the
      systems. Review of the scores plot to highlight batches manufactured using the
      same ethylcellulose raw material in the formulation, indicated that these batches
      tend to be more closely related than other randomly selected batches. This
      variability could result in potential differences in the quality of drug product
      lots made from these batches. Manufacture of a model drug product from Surelease
      batches coated using different lots of starting material revealed small
      differences in the release of a model drug, which could be detected by certain
      model dependent dissolution modeling techniques, but they were not observed when
      using model-independent techniques. This illustrates that the techniques are
      suitable for detecting and understanding excipient variability, but that, in this
      case, the product was still robust.

PMID- 30303432
TI  - Changes in serum thyroglobulin and antithyroglobulin shortly following high
      intensity focused ablation of benign thyroid nodules in patients with positive
      antithyroglobulin status.
AB  - BACKGROUND: We aimed to describe changes in serum thyroglobulin (Tg) and anti-Tg
      autoantibody shortly following high-intensity focused ultrasound (HIFU) ablation
      in patients with positive anti-Tg status by comparing them with patients with
      negative anti-Tg and to correlate them with 6-month nodule shrinkage and
      treatment success. METHODS: From 2015 to 2017, patients who underwent HIFU
      ablation of a benign thyroid nodule were analysed. Serum Tg and anti-Tg were
      checked on treatment day (baseline) and 4 days after treatment. Anti-Tg >99 IU/ml
      were considered positivity. Percentage Tg or anti-Tg change = [Level on Day-4 -
      baseline level]/[Baseline level] * 100 while nodule shrinkage was measured by
      volume reduction ratio (VRR) = [Baseline volume - volume at 6 month]/[Baseline
      volume] * 100. Treatment success was defined as VRR >50%. RESULTS: Among the 276
      eligible patients, 85 (30.8%) patients were positive for anti-Tg (Group I) while
      the others (n = 191, 69.2%) were negative (Group II). Relative to group II, Group
      I had a less significant Tg rise on Day 4 (4121.78 +/- 9321.90% vs. 5711.53 +/-
      23487.20%, p = .013). There was a fall in anti-Tg on day 4 for group I (-11.56 +/
      139.69%). This percentage anti-Tg drop significantly correlated with the 6-month
      VRR (rho = -0.602, p = .030) but was not a significant factor of treatment
      success. CONCLUSIONS: Given the fact that the percentage anti-Tg drop correlated
      significantly with 6-month nodule shrinkage in group I, monitoring early anti-Tg
      change may help to predict the 6-month nodule shrinkage in patients with positive
      anti-Tg.

PMID- 30303434
TI  - Modulation of neuromuscular synapses and contraction in Drosophila 3rd instar
      larvae.
AB  - Over the past four decades, Drosophila melanogaster has become an increasingly
      important model system for studying the modulation of chemical synapses and
      muscle contraction by cotransmitters and neurohormones. This review describes how
      advantages provided by Drosophila have been utilized to investigate synaptic
      modulation, and it discusses key findings from investigations of cotransmitters
      and neurohormones that act on body wall muscles of 3rd instar Drosophila larvae.
      These studies have contributed much to our understanding of how neuromuscular
      systems are modulated by neuropeptides and biogenic amines, but there are still
      gaps in relating these peripheral modulatory effects to behavior.

PMID- 30303435
TI  - Clinical Characteristics and Treatment of 308 Panuveitis Patients over 10 Years:
      Results from the KKESH Uveitis Survey Study Group.
AB  - PURPOSE: To describe the clinical characteristics and surgical outcomes of
      panuveitis over a 10-year period. METHODS: Data were collected on panuveitis
      etiology, treatment, surgery and change in vision. RESULTS: Overall, 308 patients
      (594 eyes) were evaluated, 54.9% with non-granulomatous and 45.1% with
      granulomatous uveitis. Fifty-four patients had infectious and 254 had non
      infectious uveitis. In infectious panuveitis, vision remained unchanged at last
      visit. The most frequent diagnosis was presumed intraocular tuberculosis (PIOTB)
      uveitis (48.1%). In the non-infectious subgroup vision increased significantly by
      2 lines at last visit (p = 0.020). The most common diagnose was Vogt-Koyanagi
      Harada (VKH) disease (38.6%). Initial therapy was oral prednisone in 86.6% with
      non-infectious etiology followed by immunosuppressive agents. Surgery secondary
      to complications (mainly cataracts) was performed in 46.7% patients. CONCLUSION:
      In Saudi Arabia, panuveitis was mainly due to VHK. PIOTB was the most common
      etiology for infectious panuveitis. Immunosuppressive therapy and surgery
      maintained BCVA in non-infectious panuveitis.

PMID- 30303436
TI  - Coadministration of 13-valent pneumococcal conjugate and quadrivalent inactivated
      influenza vaccines in adults previously immunized with polysaccharide
      pneumococcal vaccine 23: a randomized clinical trial.
AB  - Immune responses to 13-valent pneumococcal conjugate vaccine (PCV13) and
      quadrivalent inactivated influenza vaccine (QIV) in older adults may vary with
      coadministration and previous pneumococcal polysaccharide vaccination. This study
      assessed safety and noninferiority of immune responses to coadministered PCV13
      and QIV compared with each vaccine given alone. Adults >=50 years old
      preimmunized with >=1 dose of 23-valent pneumococcal polysaccharide vaccine
      (PPSV23) >=1 year before enrollment were randomized 1:1 to receive PCV13+QIV then
      placebo 1 month later or placebo+QIV then PCV13 1 month later. Administration of
      PCV13 and placebo was blinded; QIV was administered open-label. Pneumococcal
      serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) 1
      month after PCV13, and influenza hemagglutination inhibition assay GMTs 1 month
      after QIV were measured. Prespecified noninferiority was demonstrated by a lower
      bound of the 2-sided 95% CI for geometric mean ratios >0.5. Safety endpoints
      included proportions of subjects with adverse and serious adverse events. Of 882
      randomized subjects, 846 comprised the evaluable immunogenicity population.
      Immune responses to all 13 pneumococcal serotypes and all 4 influenza strains 1
      month after PCV13+QIV were noninferior to responses 1 month after each vaccine
      given alone. No safety concerns were identified. Immune responses to
      coadministered PCV13 and QIV were noninferior to responses after each vaccine
      given alone, although generally lower for coadministered PCV13. PCV13 and QIV can
      be administered concomitantly to adults >=50 years of age preimmunized with
      PPSV23.

PMID- 30303437
TI  - A molecular dynamics approach towards evaluating osmotic and thermal stress in
      the extracellular environment.
AB  - OBJECTIVE: A molecular dynamics approach to understanding fundamental mechanisms
      of combined thermal and osmotic stress induced by thermochemical ablation (TCA)
      is presented. METHODS: Structural models of fibronectin and fibronectin bound to
      its integrin receptor provide idealized models for the effects of thermal and
      osmotic stress in the extracellular matrix. Fibronectin binding to integrin is
      known to facilitate cell survival. The extracellular environment produced by TCA
      at the lesion boundary was modelled at 37  degrees C and 43  degrees C with added
      sodium chloride (NaCl) concentrations (0, 40, 80, 160, and 320 mM). Atomistic
      simulations of solvated proteins were performed using the GROMOS96 force field
      and TIP3P water model. Computational results were compared with the results of
      viability studies of human hepatocellular carcinoma (HCC) cell lines HepG2 and
      Hep3B under matching thermal and osmotic experimental conditions. RESULTS: Cell
      viability was inversely correlated with hyperthermal and hyperosmotic stresses.
      Added NaCl concentrations were correlated with a root mean square fluctuation
      increase of the fibronectin arginylglycylaspartic acid (RGD) binding domain.
      Computed interaction coefficients demonstrate preferential hydration of the
      protein model and are correlated with salt-induced strengthening of hydrophobic
      interactions. Under the combined hyperthermal and hyperosmotic stress conditions
      (43  degrees C and 320 mM added NaCl), the free energy change required for
      fibronectin binding to integrin was less favorable than that for binding under
      control conditions (37  degrees C and 0 mM added NaCl). CONCLUSION: Results
      quantify multiple measures of structural changes as a function of temperature
      increase and addition of NaCl to the solution. Correlations between cell
      viability and stability measures suggest that protein aggregates, non-functional
      proteins, and less favorable cell attachment conditions have a role in TCA
      induced cell stress.

PMID- 30303438
TI  - Human PXR-mediated transcriptional activation of CYP3A4 by "Fuzi" extracts.
AB  - OBJECTIVE: This study focused on determining whether the "Fuzi" (FZ) extracts
      from different extraction methods are related to pregnane X receptor (PXR) and
      cytochrome P450 3A4 (CYP3A4), and explore the mechanism. METHODS: FZ was
      extracted under various conditions, and the components were identified by Ultra
      Performance Liquid Chromatography/Quad Time Of Flight Mass Spectrometry (UPLC/Q
      TOF-MS). Annexin V-FITC and propidium iodide staining assays were used to measure
      the cell cytotoxicity of these extracts. Real-time PCR, western blot analysis and
      reporter gene assay were used to detect the expression changes of PXR and CYP3A4.
      RESULTS: FZ extracts were found to contain high levels of monoester-diterpene
      alkaloids (MDAs) and diester-diterpene alkaloids (DDAs). FZ extracts were
      cytotoxic. Interestingly, we found that FZ extracts and DDAs can induce the
      expressions of PXR and CYP3A4. And the MDAs can inhibit the expressions of PXR
      and CYP3A4. CONCLUSION: Different extracts of FZ can induce the expressions of
      PXR and CYP3A4 in different degrees. This may be related to the drug-drug
      interactions.

PMID- 30303439
TI  - Quantified water intake in laboratory cats from still, free-falling and
      circulating water bowls, and its effects on selected urinary parameters.
AB  - Objectives The study objectives were to determine if method of water presentation
      (still [S], circulating [C] or free-falling [FF] bowl systems) influences daily
      water consumption in cats in a controlled environment, and whether differences in
      water intake affect urine relative super saturation (RSS) for calcium oxalate and
      struvite, urine specific gravity (USG), urine osmolality (Uosmol) and urine
      volume. Methods Sixteen healthy laboratory cats fed a dry diet were individually
      housed with urine collection systems. Each cat underwent a randomized 2 week
      crossover period with all bowl systems allowing a 1 week acclimation period
      between each crossover. Water intake was measured daily by bowl weight,
      accounting for spillage and evaporation. USG and urine volume were measured
      daily, whereas other urinary parameters were measured at various time points
      throughout each 14 day crossover period. Results Fourteen cats completed the
      study. Average daily water intake (ml/kg/day), urine volume, USG and urine RSS
      for struvite and calcium oxalate were not significantly different between water
      bowls. Uosmol was significantly higher in C compared with S and FF bowl systems (
      P = 0.009 for both). Three individual cats demonstrated a significant water bowl
      preference (Cat 4: C >S, P = 0.039; Cat 10: FF >C, P = 0.005; Cat 11: S >C, P =
      0.037). Conclusions and relevance Overall, water bowl type had no appreciable
      effect on water intake. Uosmol was the only urinary parameter found to be
      significantly different, and was higher for the C bowl. The implication of this
      is unknown, considering water intake did not differ significantly between bowls.
      Alternative methods to increase water intake should be implemented beyond
      providing unique water bowls in patients where augmented water intake would be
      beneficial for disease management.

PMID- 30303440
TI  - Development of a small-scale spray-drying approach for amorphous solid
      dispersions (ASDs) screening in early drug development.
AB  - The present study details the development of a small-scale spray-drying approach
      for the routine screening of amorphous solid dispersions (ASDs). This strategy
      aims to overcome the limitations of standard screening methodologies like solvent
      casting and quench cooling to predict drug-polymer miscibility of spray-dried
      solid dispersions (SDSDs) and therefore to guarantee appropriate carrier and drug
      loading (DL) selection. A DoE approach was conducted to optimize process
      conditions of ProCept 4M8-TriX spray-drying to maximize the yield from a 100 mg
      batch of Itraconazole/HPMCAS-LF and Itraconazole/Soluplus 40:60 (w/w). Optimized
      process parameters include: inlet temperature, pump speed, drying and atomizing
      airflows. Identified process conditions derived from the DoE analysis were
      further (i) tested with Itraconazole, Naproxen and seven polymers, (ii) adapted
      for small cyclone use, (iii) downscaled to 20 mg batch production. Drug-polymer
      miscibility was systematically characterized using modulated differential
      scanning calorimetry (mDSC). Spray-drying was identified as a well-suited
      screening approach: mean yield of 10.1 to 40.6% and 51.1 to 81.0% were obtained
      for 20 and 100 mg ASD productions, respectively. Additionally, this work
      demonstrates the interest to move beyond conventional screening approaches and
      integrate spray-drying during screening phases so that a greater prediction
      accuracy in terms of SDSDs miscibility and performance can be obtained.

PMID- 30303441
TI  - Response to PCV13 vaccination in patients with multiple myeloma versus healthy
      controls.
AB  - Infections are a major cause of morbidity and mortality in individuals with
      multiple myeloma (MM). These individuals exhibit humoral dysfunction and show a
      suboptimal response to pneumococcal polysaccharide vaccine (PPV23). Since
      pneumococcal conjugate vaccine (PCV13) elicits a T cell dependent response, it is
      recommended in patients with multiple myeloma. This study compares the initial
      response to PCV13 and durability of the response at 6 months in patients with
      multiple myeloma versus normal controls. Seven patients with multiple myeloma and
      18 control patients were enrolled in the study. Streptococcal pneumonia serotype
      IgG titers were drawn at baseline, day 30, and day 180 after MM patients and
      controls received PCV13. Although vaccination with PCV13 produced a similar
      initial response in patients with multiple myeloma compared to control subjects,
      the duration of response may have waned in patients with multiple myeloma as
      compared to control subjects.

PMID- 30303442
TI  - High Mobility Group Protein B1 (HMGB1) and Interleukin-1beta as Prognostic
      Biomarkers of Epilepsy in Children.
AB  - The present study examined whether serum biomarkers can predict the prognosis of
      childhood epilepsy, including seizure frequency, electroencephalographic (EEG)
      changes, and cognitive impairment. We measured serum concentrations of high
      mobility group protein B1 (HMGB1), interleukin-1beta (IL-1beta), S100 calcium
      binding protein B (S-100B), glial fibrillary acidic protein (GFAP), and alpha1
      antichymotrypsin (AACT) in 180 children with new-onset epilepsy and 40 healthy
      children. Cognitive evaluations were performed 18 months after the initial
      seizure episodes at diagnosis (ie, baseline visit). The relationship between
      serum biomarkers and epilepsy prognosis was investigated using Pearson
      correlation coefficients, logistic regression analyses, and receiver operating
      characteristic curves. Sixty-seven patients had generalized tonic-clonic
      seizures, 92 had focal motor seizures, and 21 had epileptic spasms. Serum
      concentrations of HMGB1, IL-1beta, S-100B, and GFAP were significantly higher in
      the epilepsy group within 24 hours of a seizure episode than in the control
      group. Furthermore, HMGB1 and IL-1beta were significant predictors of epilepsy
      prognosis. Receiver operating characteristic curve analysis revealed that HMGB1
      could more accurately predict seizure frequency than IL-1beta; when the serum
      concentration of HMGB1 was >9.625 ng/mL, there was 80.6% sensitivity and 92.5%
      specificity for predicting seizure frequency reduction. In conclusion, HMGB1 and
      IL-1beta have a predictive value for epilepsy prognosis in children.

PMID- 30303443
TI  - Evolution of a comprehensive, orthogonal approach to sequence variant analysis
      for biotherapeutics.
AB  - Amino acid sequence variation in protein therapeutics requires close monitoring
      during cell line and cell culture process development. A cross-functional team of
      Pfizer colleagues from the Analytical and Bioprocess Development departments
      worked closely together for over 6 years to formulate and communicate a
      practical, reliable sequence variant (SV) testing strategy with state-of-the-art
      techniques that did not necessitate more resources or lengthen project timelines.
      The final Pfizer SV screening strategy relies on next-generation sequencing (NGS)
      and amino acid analysis (AAA) as frontline techniques to identify mammalian cell
      clones with genetic mutations and recognize cell culture process media/feed
      conditions that induce misincorporations, respectively. Mass spectrometry (MS)
      based techniques had previously been used to monitor secreted therapeutic
      products for SVs, but we found NGS and AAA to be equally informative, faster,
      less cumbersome screening approaches. MS resources could then be used for other
      purposes, such as the in-depth characterization of product quality in the final
      stages of commercial-ready cell line and culture process development. Once an
      industry-wide challenge, sequence variation is now routinely monitored and
      controlled at Pfizer (and other biopharmaceutical companies) through increased
      awareness, dedicated cross-line efforts, smart comprehensive strategies, and
      advances in instrumentation/software, resulting in even higher product quality
      standards for biopharmaceutical products.

PMID- 30303444
TI  - Optimization and partial characterization of ca-independent alpha-amylase from
      Bacillus amyloliquefaciens BH1.
AB  - Strain Bacillus amyloliquefaciens BH1 was evaluated for the generation of alpha
      amylase. Culture conditions and medium components were optimized by a statistical
      approach for the optimal generation of alpha-amylase with response surface
      methodology (RSM) method. The Plackett-Burman (PB) design was executed to select
      the fermentation variables and Central composite design (CCD) for optimizing
      significant factors influencing production. The optimum levels for highest
      generation of alpha-amylase activity (198.26 +/- 3.54 U/mL) were measured. A 1.69
      fold improve generation was acquired in comparison with the non-optimized.
      Partial characterization of the alpha-amylase indicated optimal pH and
      temperature at 7.0 and 40  degrees C, respectively. Crude alpha-amylase
      maintained a constant pH range 5.0-8.0 and 30-70  degrees C. The alpha-amylase
      was independent of Ca2+, and the activity was inhibited by Fe3+, Co2+, Cu2+, and
      Hg2+. The thermo and pH stability of the alpha-amylase indicate its extensive
      application in the food and pharmaceutical industries.

PMID- 30303445
TI  - Impact of trial design and patient heterogeneity on the identification of
      clinically effective therapies for progressive MS.
AB  - Clinically effective immunomodulatory therapies have been developed for relapsing
      remitting multiple sclerosis (RRMS), but they have generally not translated to a
      corresponding slowing of disability accumulation in progressive forms of multiple
      sclerosis (MS). Since disability is multifaceted, progressive patients are
      heterogeneous, and the drivers of disease progression are still unclear, it has
      been difficult to identify the most informative outcome measures for progressive
      trials. Historically, secondary outcome measures have focused on inflammatory
      measures, which contributed to the recent identification of immunomodulatory
      therapies benefiting younger patients with more inflammatory progressive MS.
      Meanwhile, agents capable of treating late-stage disease have remained elusive.
      Consequently, measures of neurodegeneration are becoming common. Here, we review
      completed clinical trials testing immunomodulatory therapies in primary
      progressive multiple sclerosis (PPMS) or secondary progressive multiple sclerosis
      (SPMS) and discuss the features contributing to trial design variability in
      relation to trial outcomes, and how efforts toward better patient stratification
      and inclusion of reliable progression markers could improve outcomes.

PMID- 30303446
TI  - Fungal co-culture increases ligninolytic enzyme activities: statistical
      optimization using response surface methodology.
AB  - The optimization of ligninolytic enzyme (LE) activities in a novel fungal co
      culture between Pycnoporus sanguineus and Beauveria brongniartii were studied
      using a Plackett-Burman experimental design (PBED) and a central composite design
      (CCD). In addition, H2O2 role was analyzed. Laccase (EC. 1.10.3.2) and MnP (EC
      1.11.1.14) activities of P. sanguineus increased 6.0- and 2.3-fold, respectively,
      in the co-culture with B. brongniartii. The H2O2 content was higher in the co
      culture (0.33-7.12-fold) than in the P. sanguineus monoculture. The PBED revealed
      that yeast extract (YE), FeSO4, and inoculum amount were significant factors for
      laccase and MnP activities and H2O2 production in the co-culture, which increased
      by 8.2-, 5.2- and 1.03-fold, respectively. The YE and FeSO4 were studied using a
      CCD to optimize the studied response variables. Laccase activity was enhanced 1.5
      fold by CCD, the optimal amount of YE was 0.366 g L-1. Quadratic term of FeSO4
      modulated MnP activity and was associated with a 4.28-fold increase compared to
      the PBED. Both YE and its quadratic term significantly affected H2O2 production;
      however, the CCD did not enable an increase in H2O2 production. Pearson
      correlation indicated an increase in laccase (r2=0.4411, p = 0.0436) and MnP
      (r2=0.5186, p = 0.0198) activities following increases in H2O2 in the co-culture
      system.

PMID- 30303447
TI  - EEG dynamics of spontaneous stimulus-independent thoughts.
AB  - In this study, we aimed to compare the oscillatory dynamics accompanying self
      referential and non-self-referential stimulus-independent thoughts.
      Electroencephalograms were recorded in 30 healthy participants who were asked to
      press buttons classifying their spontaneous thoughts as self-referential or non
      self-referential. EEG data were analyzed using independent component analysis in
      conjunction with dipole localization. Self-referential thoughts, as compared to
      non-self-referential thoughts, were accompanied by more pronounced decreases of
      theta, alpha, and beta spectral power in the anterior hub of the default-mode
      network, in the left lateral prefrontal, motor/somatosensory, and temporal
      cortices. These oscillatory dynamics are interpreted as a reflection of
      autobiographical memory retrieval intrinsic to self-referential thoughts.
      Abbreviations: BA: Brodmann area; BOLD: blood oxygenation level-dependent; DMN:
      default mode network; EEG: electroencephalogram; ERSP: event-related spectral
      perturbations; fMRI: functional magnetic resonance imaging; PCC: posterior
      cingulate cortex; PET: positron emission tomography; PFC: prefrontal cortex; SIT:
      stimulus-independent thought; WM: working memory.

PMID- 30303448
TI  - Accuracy of advanced CT imaging in prediction of functional outcome after
      endovascular treatment in patients with large-vessel occlusion.
AB  - Background and purpose Computed tomography perfusion (CTP) and multiphase CT
      angiography (mCTA) help selection for endovascular treatment (EVT) in anterior
      ischemic stroke (AIS). Our aim was to investigate the ability of perfusion maps
      and collateral score to predict functional outcome after EVT. Patients and
      methods Patients with M1-middle cerebral artery occlusion, evaluated by mCTA and
      CTP and treated with EVT within six hours of onset, were enrolled. Perfusion
      parametric maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and
      time to maximum of tissue residue function ( Tmax) were generated; areas of
      altered perfusion were manually outlined to obtain volumes CBFv, CBVv, [Formula:
      see text] and [Formula: see text]. Diffusion-weighted imaging (DWI) at 24-36
      hours was used to manually outline the ischemic core (volume: DWIv). Collateral
      vessels were assessed on mCTA considering extent and delay of maximal enhancement
      (six-point scale). Functional outcome was evaluated by modified Rankin Scale
      score at three months. Volumes in good and poor outcome groups were compared by
      Wilcoxon rank-sum test t, and their discriminative ability for outcome was
      determined by receiver operating characteristic analysis. A logistic regression
      model, including Tmax, CBF and collaterals, was used to differentiate good and
      poor outcome. Results Seventy-one patients (mean age 75 +/- 11 years, range 45-99
      years) were included. [Formula: see text], [Formula: see text], CBVv, CBFv and
      DWIv were statistically different between the two groups. CBF had the best
      discriminative value for good and poor outcome (area under the curve (AUC) 0.73;
      64.5% sensitivity; 74.4% specificity); the logistic regression model might be
      promising (AUC 0.79, 64.5% sensitivity, 82.1% specificity). Conclusions In
      patients with AIS, the combined use of CTP and mCTA predicts functional outcome
      of EVT and might allow better selection.

PMID- 30303449
TI  - The high expression of Aspergillus pseudoglaucus protease in Escherichia coli for
      hydrolysis of soy protein and milk protein.
AB  - The hydrolysates of soy protein and milk protein are nutritional and functional
      food ingredients. Aspergillus pseudoglaucus aspergillopepsin I (App) is an acidic
      protease, including signal peptide, propeptide, and catalytic domain. Here, we
      cloned the catalytic domain App with or without propeptide in Escherichia coli.
      The results showed that the App without propeptide was not expressed or did not
      exhibit activity and App with propeptide (proApp) was highly expressed with a
      specific activity of 903 U/mg. Moreover, the denaturation temperature of proApp
      was 4.1  degrees C higher than App's. The proApp showed 104 U/mg and 252 U/mg
      hydrolysis activities towards soy protein and milk protein under acidic
      conditions. By RP-HPLC analysis, the peptides obtained from the hydrolysates of
      soy protein and milk protein were hydrophilic peptides. This work first
      demonstrates efficient proteolysis of soy protein and milk protein through the
      functional expression of full-length proApp, which will likely have valuable
      industrial applications.

PMID- 30303450
TI  - Calcified brain metastatic adenocarcinoma: A case report and review of the
      literature.
AB  - Introduction Calcification in brain metastasis occurs rarely so it is reported in
      approximately 1% of surgical and 6.6% of autopsy specimens. Here we report a new
      case of brain metastasis with calcification. Case presentation A 44-year-old
      woman presented with a generalized tonic-clonic seizure with no neurological
      deficit on physical examination. Brain imaging demonstrated a hyperdense lesion
      on computed tomography scan and hyposignal and rim enhancement on T1, T2 and T1
      with gadolinium injection sequence images in the right parieto-occipital lobe.
      Intraoperatively, there was a well-defined solid homogenous calcified mass within
      brain parenchyma. The lesion that resembled a meningioma was totally resected.
      The histopathological examination revealed metastatic adenocarcinoma. Conclusion
      Metastatic brain lesions should be in the differential diagnosis of a solitary
      calcified brain mass, although it occurs rarely. It is important to differentiate
      it radiologically from intralesional haemorrhage.

PMID- 30303451
TI  - Carboxymethyl cellulase production optimization from Glutamicibacter arilaitensis
      strain ALA4 and its application in lignocellulosic waste biomass
      saccharification.
AB  - In this context, carboxymethyl cellulase (CMCase) production from Glutamicibacter
      arilaitensis strain ALA4 was initially optimized by one factor at a time (OFAT)
      method using goat dung as proficient feedstock. Two-level full factorial design
      (25 factorial matrix) using first-order polynomial model revealed the significant
      (p < 0.05) influence of pH, moisture, and peptone on CMCase activity. Central
      composite design at N = 20 was further taken into account using a second-order
      polynomial equation, and thereby liberated maximum CMCase activity of 4925.56 +/-
      31.61 U/g in the goat dung medium of pH 8.0 and 100% moisture containing 1% (w/w)
      peptone, which was approximately two fold increment with respect to OFAT method.
      Furthermore, the partially purified CMCase exhibited stability not only at high
      pH and temperature but also in the presence of varied metal ions, organic
      solvents, surfactants, and inhibitors with pronounced residual activities. The
      enzymatic hydrolysis using partially purified CMCase depicted the maximum
      liberation of fermentable sugars from alkali pretreated lignocellulosic wastes
      biomass in the order of paddy straw (13.8 +/- 0.15 mg/g) > pomegranate peel (9.1
      +/- 0.18 mg/g) > sweet lime peel (8.37 +/- 0.16 mg/g), with saccharification
      efficiency of 62.1 +/- 0.8, 40.95 +/- 0.4, and 37.66 +/- 0.4%, respectively after
      72 hr of treatment.

PMID- 30303452
TI  - Cloning, large-scale production and characterization of fusion protein (P-TUFT
      ALT-2) of Brugian abundant larval transcript-2 with tuftsin in Pichia pastoris.
AB  - Lymphatic filariasis is a "disease of poor people" due to a large section of
      affected people with economic backwardness. Therefore, successful elimination of
      this disease requires a cost-effective prophylactic agent such as vaccine along
      with conventional drugs. The Abundant Larval Transcript-2 (BmALT-2) protein of
      Brugia malayi has been recognized as the most potential vaccine candidate.
      Tuftsin, a tetra-peptide immunopotentiator has already shown the enhanced
      immunogenicity of various vaccine antigens in earlier studies. This study deals
      with the development of tuft-alt-2 fusion construct and a suitable culture
      condition for its large-scale production in Pichia pastoris. The recombinant P.
      pastoris/tuft-alt-2 with 9-11 copies of the gene construct exhibited the highest
      expression level. The molecular weight of P-TUFT-ALT-2 was determined as 28 kDa
      in SDS-PAGE including 3 kDa due to glycosylation. The dry cell biomass was 57.4
      gL-1 in the bioreactor. The P-TUFT-ALT-2 expression was measured as about 35 mg L
      1, which was 102% higher than flask culture. The P-TUFT-ALT-2 produced the
      highest 65,000 IgG peak titer in Balb/c mice. Moreover, P-TUFT-ALT-2 exhibited
      about 9.46% higher splenocyte proliferation than E. coli expressed E-ALT-2 alone.
      The enhanced secreted production of P-TUFT-ALT-2 in bioreactor would step up its
      commercialization as an inexpensive commercial vaccine for human lymphatic
      filariasis.

PMID- 30303453
TI  - Catalytic and thermodynamic properties of beta-glucosidases produced by
      Lichtheimia corymbifera and Byssochlamys spectabilis.
AB  - The objective of the present study was to optimize parameters for the cultivation
      of Lichtheimia corymbifera (mesophilic) and Byssochlamys spectabilis
      (thermophilic) for the production of beta-glucosidases and to compare the
      catalytic and thermodynamic properties of the partially purified enzymes. The
      maximum amount of beta-glucosidase produced by L. corymbifera was 39 U/g dry
      substrate (or 3.9 U/mL), and that by B. spectabilis was 77 U/g (or 7.7 U/mL). The
      optimum pH and temperature were 4.5 and 55  degrees C and 4.0 and 50  degrees C
      for the enzyme from L. corymbifera and B. spectabilis, respectively. beta
      Glucosidase produced by L. corymbifera was stable at pH 4.0-7.5, whereas the
      enzyme from B. spectabilis was stable at pH 4.0-6.0. Regarding the
      thermostability, beta-glucosidase produced by B. spectabilis remained stable for
      1 h at 50  degrees C, and that from L. corymbifera was active for 1 h at 45 
      degrees C. Determination of thermodynamic parameters confirmed the greater
      thermostability of the enzyme produced by the thermophilic fungus B. spectabilis,
      which showed higher values of DeltaH, activation energy for denaturation (Ea),
      and half-life t(1/2). The enzymes were stable in the presence of ethanol and were
      competitively inhibited by glucose. These characteristics contribute to their use
      in the simultaneous saccharification and fermentation of vegetable biomass.

PMID- 30303454
TI  - Top cited research over fifteen years in Sports Biomechanics.
AB  - This study tested the hypothesis of the strong scholar perception of the journal
      Sports Biomechanics with a bibliometric analysis of top-cited articles. Three
      major databases, Google Scholar, Scopus and Web of Science, were searched for the
      most cited articles published in Sports Biomechanics for the first 15 years (2002
      2016) of publication. The top 20 (4%) cited articles from each database were
      qualitatively analysed for research themes and descriptive statistics calculated
      for citations and citation rates. The top-cited articles published in Sports
      Biomechanics had high citation rates and included several citation classics,
      indicating strong contributions to the advancement of knowledge in applied
      biomechanics and beyond. The results support previous high ratings of the journal
      by sport and exercise biomechanics scholars and refute the biased and lower
      ranking based on the Web of Science Impact Factor. There was moderate (40-70%)
      agreement on the top 20 cited articles between the three databases due to
      differences in indexing and temporal coverage.

PMID- 30303455
TI  - Ecotoxicological risk assessment of contaminated soil from a complex of ceramic
      industries using earthworm Eisenia fetida.
AB  - The aim of this study was to determine ecotoxicological parameters for
      biomonitoring of environmental risk of native soils from a ceramic industrial
      area that had been contaminated with cadmium (Cd) and chromium (Cr) by using the
      earthworm, Eisenia fetida. Initially, lab tests were conducted to compare
      earthworm (Eisenia fetida) growth, survival, morphology, behavior, and
      reproduction rates following exposure to six concentrations of contaminated soil
      at 0%, 6.25%, 12.5%, 25%, 50%, or 100% mixed in artificial soil and cow dung
      following a 28-d incubation period. The second experiment consisted of utilizing
      Eisenia fetida in a predetermined lowest observed effect concentration to measure
      heavy metals bioaccumulation from superficial soil collected from a ceramic
      industrial area following a 56-d exposure. Data demonstrated that in the lab
      earthworms maintained at 6.25% of contaminated soil, exhibited significant
      increase in mean weight, bioaccumulation of Cd and Cr associated with a
      significant decrease in the amount of Cd and Cr in the soil. At field testing,
      similar results that were observed as in the lab as evidenced by rise in mean
      weight, higher levels of Cd and Cr in the earthworm tissue accompanied by
      significant fall in soil levels of Cd and Cr. In conclusion, at tested relevant
      environmental concentrations, the use of Eisenia fetida for assessing
      ecotoxicological risk arising from contaminated soil due to ceramic industrial
      pollutant emissions was found to be an effective tool for biomonitoring program.

PMID- 30303456
TI  - Evaluation of the anti-oxidant property and cytotoxic potential of the
      metabolites extracted from the bacterial isolates from mangrove Forest and
      saltern regions of South India.
AB  - The objective was to evaluate the anticancer and antioxidant activities of the
      methanolic extracts of halophilic bacteria, isolated from soil samples of
      Marakkanam saltern and Pichavaram mangrove forest, India. Radical Scavenging
      activity, reducing power, and metal ion chelation ability was used to evaluate
      the antioxidant potential of the metabolic extracts, whereas cell viability was
      determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay. The methanolic extract of Bacillus VITPS7 exhibited significant
      antioxidant property. Bacillus VITPS14 and Bacillus VITPS16 extracts were
      cytotoxic against HeLa cell lines but not to A549 cell lines. Colorimetric assays
      for the presence of specific metabolites including, total flavonoid and beta
      carotene content were performed. The presence of these specific classes of
      metabolites was confirmed by UV-Visible spectrophotometry, Nuclear Magnetic
      Resonance (NMR) spectroscopy and Gas Chromatography-Mass Spectrometry (GC-MS).
      Specific NMR signals revealed the presence of aromatic and unsaturated
      metabolites whereas GC-MS analysis indicated the presence of metabolites such as
      squalene and methyl hexadeconate. The present study thus reports for the first
      time the presence of squalene in Bacillus VITPS12 and Planococcus maritimus
      VITP21, in addition to other metabolites that contribute to the observed
      antioxidant or/and cytotoxicity, thus revealing the therapeutic potential of
      these selected halophilic bacterial isolates.

PMID- 30303457
TI  - Aqueous two phase partitioning of Pisum sativum lectin in PEG/citrate salt
      system.
AB  - Pisum sativum lectin (Psl) is a metalloprotein which is in the center of research
      interest because of its HIV-1 reverse transcriptase inhibitory activity and
      mitogenic activity. The application of this lectin in various fields demands the
      economically feasible and scalable purification strategy other than affinity
      chromatography. The suitability of aqueous two phase system (ATPS) composed of
      poly ethylene glycol (PEG) with different salts (sodium citrate, potassium
      citrate, and ammonium citrate) was evaluated for better partitioning of Psl. The
      significant factors such as molar mass and concentration of PEG, type and
      concentration of salts, the effect of tie line length (TLL), ionic strength, and
      pH were studied to select a suitable system for better partitioning of Psl. ATPS
      comprising of 18% PEG 6000, 16% sodium citrate, 1% NaCl at the operating
      condition of pH 8, 40.23% of TLL, and the volume ratio of 1.32 was found to be
      the best system which gave a maximum partition coefficient and yield of 14.5% and
      98.66%, respectively.

PMID- 30303459
TI  - Brain magnetic resonance imaging findings in postpartum headache.
AB  - Objectives The objectives were to determine the frequency of abnormal magnetic
      resonance imaging findings in patients with postpartum headache and related
      factors. Methods A total of 102 patients with postpartum headache underwent brain
      magnetic resonance imaging study. The images were examined by a blinded
      radiologist. The related demographic, obstetric and headache-related factors were
      recorded. The multiple logistic regression model was used to determine the
      predictive factors. Results Abnormal magnetic resonance imaging findings were
      observed in 42 of 102 patients (41.2%, 95% confidence interval = 31.6 to 50.7%).
      The most common finding was sinusitis (10 of 42 patients, 23.8%, 95% confidence
      interval = 15.5 to 32%). Then, posterior reversible encephalopathy syndrome (six
      of 42 cases, 14.2%, 95% confidence interval = 7.4 to 20.9%), cerebral venous
      thrombosis (four of 42 cases, 9.5%, 95% confidence interval = 3.8 to 15.1%), and
      subarachnoid hemorrhage (four of 42 cases, 9.5%, 95% confidence interval = 3.8 to
      15.1%) were most prevalent findings. Convulsions (odds ratio of 3.39) and
      initiation of headache earlier than 5 days postpartum (odds ratio of 0.29) were
      significant predictive factors. Conclusion Abnormal brain magnetic resonance
      imaging findings were seen in a considerable number of patients with postpartum
      headache. When headache starts in the first 5 days postpartum and accompanied by
      convulsions, there are likely to be abnormal magnetic resonance imaging findings.

PMID- 30303458
TI  - A global view of Gyroporus: molecular phylogenetics, diversity patterns, and new
      species.
AB  - Gyroporus (Gyroporaceae, Boletales) is a highly diverse genus of poroid
      ectomycorrhizal mushrooms with a nearly worldwide distribution. Previous attempts
      to unravel the diversity within this genus proved difficult due to the presence
      of semicryptic species and ambiguous results from analysis of ribosomal RNA
      markers. In this study, we employ a combined morphotaxonomic and phylogenetic
      approach to delimit species and elucidate geographic and evolutionary patterns in
      Gyroporus. For phylogenetic analyses, the protein-coding genes atp6
      (mitochondrial adenosine triphosphate [ATP] synthase subunit 6) and rpb2 (nuclear
      second largest subunit of RNA polymerase II) were selected based on their utility
      in studies of Boletales. We infer several distinct clades, most notably one
      corresponding to G. castaneus as a speciose Northern Hemisphere group, another
      unifying G. cyanescens and like entities, and a third group unifying G.
      longicystidiatus and a New World sister species. Also notable is the recovery of
      a sister relationship between the cyanescens and longicystidiatus clades. We
      formally describe five new species of Gyroporus, outline a number of provisional
      species, and briefly discuss distributional patterns. This study provides an
      important scaffold for future work on this well-known but poorly understood genus
      of fungi.

PMID- 30303460
TI  - Trauma-Informed Care and Posttraumatic Growth Among Bereaved Youth: A Pilot
      Study.
AB  - Although a fair amount has been written about posttraumatic stress disorder among
      bereaved children and adolescents, less has been written about posttraumatic
      growth (PTG) and its predictors among this population. This study examines
      predictors of PTG and the impact of trauma-informed care on PTG among bereaved
      youth. A preexperimental, pretest-posttest design was applied to measure PTG
      among bereaved children ( N = 32) before and after attending a healing camp that
      provides trauma-informed care. A regression model was applied to examine
      predictors of PTG. Results showed that children participating in the camp
      increased their PTG scores to a statistically significant degree. Circumstance of
      death (sudden or expected) was a predictor in this study. The results are
      discussed in relation to limitations, implications for future research, and
      practice.

PMID- 30303461
TI  - Comparing Suicide Risk Factors Among Individuals with a History of Aborted,
      Interrupted, and Actual Suicide Attempts.
AB  - Recent standardized nomenclature has suggested distinctions among aborted,
      interrupted, and actual suicide attempts. This study examined differences in self
      reported symptoms among individuals with a history of aborted, interrupted, and
      actual suicide attempts. 167 young adults with a history of suicidality completed
      self-report measures of suicide attempt history and current symptoms, a clinical
      interview assessing past suicidal behavior, and a pain tolerance task. Only 78.8%
      of participants who initially reported a suicide attempt history were classified
      as suicide attempters following the clinical interview. Individuals who reported
      only aborted attempts during the clinical interview reported less severe clinical
      symptoms than those reporting a history of at least one actual attempt.
      Individuals with a history of actual suicide attempts may represent a more
      clinically severe group than those with a history of aborted attempts only.

PMID- 30303462
TI  - Implementation science and prevention in action: Application in a post-permanency
      world.
AB  - : This article describes how implementation science and intervention research
      guided the process of selecting and implementing an evidence-informed
      intervention (Tuning in to Teens; TINT). TINT was provided as a selective
      prevention effort offered to families with youth aged 10 to 13 years old, with
      characteristics that suggest an elevated risk for post-permanency discontinuity.
      Usability testing findings: Contact was made with 54% of families, and 12%
      participated in the intervention. Multivariate results found no statistically
      significant differences between families who responded to outreach efforts and
      those who did not; families who participated in TINT and those who did not.
      IMPLICATIONS: Large public child welfare systems wanting to implement evidence
      informed interventions can follow the steps detailed in this paper for selecting,
      adapting and implementing an intervention. Further, providers that seek to offer
      post adoption and guardianship services, a growing service need, may gain some
      insights into activities that promote service usage with this population.

PMID- 30303464
TI  - Postural control of Parkour athletes compared to recreationally active subjects
      under different sensory manipulations: A pilot study.
AB  - In Parkour activity, the aim is to move from one place to another as quickly and
      efficiently as possible by running, climbing, swinging, vaulting, rolling,
      crawling and jumping on tiny obstacles ... . Performing these actions places a
      great demand on the postural control system. The purpose of the present study was
      to investigate postural control of Parkour practitioners - called Traceurs -
      compared to recreationally active (RA) subjects in different postural conditions
      after manipulating the visual and/or proprioceptive sensory inputs. Ten Traceurs
      (mean experience 5.9 +/- 0.9 years; >5 hours per week) and 10 RA subjects
      participated in this study. We measured the centre of pressure area (CoPA) of the
      upright standing bipedal and unipedal postures in different postural conditions:
      on a firm and on a foam surfaces; on an oscillating surface in the sagittal plane
      and in the frontal plane in eyes open and eyes closed. To evaluate vision
      contribution, the Romberg index (RI) was calculated. Results showed that Traceurs
      presented a significant (P < .001) lower CoPA values compared to RA subjects in
      eyes closed condition, suggesting that they were able to maintain a better
      balance control when vision is removed. Traceurs seems to be less dependent on
      visual cues (lower RI values) and proprioceptive inputs for maintaining balance
      than RA subjects. According to our study, Parkour training (experience for at
      least five years with a minimum of five hours per week) may improve postural
      abilities of young adult practitioners in specific postural conditions.

PMID- 30303463
TI  - Synthesis and characterization of albumin imprinted polymeric hydrogel membranes
      for proteomic studies.
AB  - In this presented study, a novel molecularly imprinted polymeric hydrogel
      membranes (PHMs) were developed to use for the albumin depletion studies. For
      this, albumin imprinted poly(2-hydroxyethyl methacrylate-N-methacryloyl-(L)
      phenylalanine methyl ester) polymeric hydrogel membranes [p(HEMA-MAP) PHMs] were
      synthesized by the photopolymerization technique, and then characterized by SEM,
      EDX, FT-IR and swelling studies. Synthesized PHMs had spherical structure and the
      MAP monomer incorporation onto the PHMs was determined by EDX analysis by using
      nitrogen stoichiometry. Also, the swelling ratio of the albumin imprinted p(HEMA
      MAP) PHMs was determined as 215%. The optimum albumin adsorption condition
      (adsorption capacity, medium pH, adsorption rate, temperature, ionic strength)
      were studied and the maximum albumin adsorption capacity was found to be as 34.28
      mg/g PHMs. Selectivity experiments were also carried out with the presence of the
      competitive proteins such as lysozyme and amylase, and the results demonstrated
      that the albumin imprinted p(HEMA-MAP) PHMs showed high affinity towards the BSA
      molecules than the competitive proteins of lysozyme and amylase. Adsorbed albumin
      was desorbed from the PHMs by 1.0 M of NaCl, and the reusability of the imprinted
      PHMs was also demonstrated for five successive adsorption-desorption cycles
      without any significant loss in the albumin adsorption capacity. As an
      application, sodium-dodecyl sulfate polyacrylamide gel electrophoresis was used
      to indicate the albumin depletion efficiency of albumin imprinted p(HEMA-MAP)
      PHMs. This presented study showed that, these imprinted membranes are promising
      for proteomic studies and applications, and can be used for the investigations
      for human diagnostics.

PMID- 30303466
TI  - The Relationship Between Residential Mobility and Behavioral Health Service Use
      in a National Sample of Adults With Mental Health and/or Substance Abuse
      Problems.
AB  - OBJECTIVE: Individuals with mental health and/or substance abuse problems
      experience disparities in health care utilization. While previous studies have
      focused on individual and social determinants of health care use in these
      populations, few have investigated the role of residential stability, especially
      in relation to different types of service use (i.e., inpatient vs. outpatient
      treatment). The present study examined the relationship between residential
      mobility, defined as the number of residential relocations in the past year, and
      past-year use of four types of behavioral services (i.e., inpatient and
      outpatient mental health services, inpatient and outpatient substance abuse
      services) among a national sample of adults with mental health and/or substance
      abuse problems. METHODS: Data were drawn from the 2011-2014 National Survey of
      Drug Use and Health (unweighted N = 43,411). Based on prior literature and
      theory, we hypothesized that individuals who frequently relocate are more likely
      to use inpatient services and are less likely to use outpatient services.
      Logistic regression analyses were conducted and all models controlled for
      predisposing, need, and enabling factors. RESULTS: Compared to individuals who
      did not move in the past year, those who moved three or more times were more
      likely to report using inpatient mental health and substance abuse services. The
      relationship between residential mobility and outpatient mental health and
      substance use service use is not significant. CONCLUSIONS: The findings highlight
      the importance of understanding housing stability as a predictor factor of
      service use and access. Future research is needed to shed light on the pathway
      through which residential mobility affects behavioral health service utilization.

PMID- 30303465
TI  - Enhanced immobilization of mercury (II) from desulphurization wastewater by EDTA
      functionalized graphene oxide nanoparticles.
AB  - Graphene oxide (GO) is a new promising nanometer material in a superconductor and
      wastewater heavy metal ions removal for its functionalized groups.
      Ethylenediaminetetraacetic acid functionalized graphene oxide complexes (EDTA-GO)
      was produced by a realizable silanization chemical reaction. Characteristics of
      Hg(II) removal in desulphurization wastewater was also under investigation. The
      chemical composition and microstructures of the EDTA-GO adsorbents were
      characterized by X-ray photoelectron spectroscopy (XPS), Transmission electron
      microscope (TEM), Scanning Electron Microscopy (SEM) analyses. To investigate the
      performance of EDTA-GO adsorbents on adsorption of Hg(II) in wastewater of wet
      flue gas desulphurization (WFGD), experiments were performed to optimize the main
      influence factors such as reaction temperatures (35-70 degrees C), pH values(2
      13), contact time (0-120 min), initial Hg(II) concentrations(800 ug/L) and
      adsorbent doses (20-50 mg/L). The maximum uptake removal efficiency (97.14%) was
      achieved under the optimal conditions at the pH of 7, the temperature of 70
      degrees C, the Hg(II) concentration of 1200 MUg/L and the EDTA-GO dose of 40
      mg/L. The kinetic data fitting results were well consistent with the pseudo
      second-order model (R2 = 0.99997) and a spontaneous and endothermic adsorption
      reaction was elaborated by thermodynamics studies (DeltaG < 0, DeltaH > 0, DeltaS
      > 0). The experiments of recycled adsorbents by HCl generation were carried out
      to obtain the performance of the reused EDTA-GO adsorbent, the fourth
      regenerative adsorption efficiency still maintained 80.4%, which indicated that
      excellent potential application in desulphurization wastewater treatment.

PMID- 30303467
TI  - Summary of the Third World Congress on Thyroid Cancer.

PMID- 30303468
TI  - Fusarium subtropicale, sp. nov., a novel nivalenol mycotoxin-producing species
      isolated from barley (Hordeum vulgare) in Brazil and sister to F.
      praegraminearum.
AB  - Surveys were conducted in commercial wheat and barley fields in the south central
      production regions of state of Parana, Brazil, from 2011 to 2015. Spikes
      displaying visible Fusarium head blight symptoms were collected and the pathogen
      isolated from the tissues. The 754 Fusarium isolates recovered were identified by
      a high-throughput multilocus genotyping assay (MLGT) designed to identify
      trichothecene toxin-producing fusaria (i.e., formerly B-clade, but referred to
      here as F. sambucinum species complex lineage 1 [FSAMSC-1]) together with
      sequencing a portion of the translation elongation factor 1-alpha (TEF1) gene.
      One strain was discovered that appeared to be closely related to but
      phylogenetically distinct from F. praegraminearum based on the relatively low
      97.7% TEF1 identity and positive genotype obtained with one of the two F.
      praegraminearum species-specific MLGT probes. Molecular phylogenetic analyses of
      a 10-gene data set resolved this novel FSAMSC-1 species and F. praegraminearum as
      sisters. Formally described herein as F. subtropicale, it is phenotypically
      distinct from the 22 other FSAMSC-1 species in that it produces mostly 1-3
      septate macroconidia. Whole-genome sequence data were used to predict its
      potential to produce mycotoxins. Chemical analyses confirmed that F. subtropicale
      could produce the mycotoxins 4,15-diacetylnivalenol, butenolide, culmorin, and
      fusarin C in vitro, and the pathogenicity experiment revealed that F.
      subtropicale could infect but not spread in susceptible hard red spring wheat
      cultivar "Norm."

PMID- 30303470
TI  - Screening for risk of low energy availability in athletic and recreationally
      active females in Ireland.
AB  - INTRODUCTION: Low energy availability (LEA) results in physiological adaptations,
      which can contribute to unfavourable health outcomes. Little information exists
      on risk of LEA in active individuals competing in different sports or levels of
      competition. The aims of this study were to (1) identify risk of LEA in females
      competing at different levels of competition and (2) investigate associations
      between risk of LEA, illness and dietary habits. METHODS: The validated
      questionnaire, 'Low Energy Availability in Females Questionnaire' was distributed
      online (November 2016-February 2017) to assess risk of LEA. Twenty-nine
      additional questions collected information on demographics, illness history and
      dietary habits. Participants were considered at risk of LEA if they attained a
      score of >= 8 and were grouped into: (i) international; (ii) provincial/inter
      county; (iii) competitive; and (iv) recreationally active. Chi-square and
      logistic regression analyses were used to explore differences between those at
      risk or not at risk of LEA. RESULTS: Risk of LEA was identified in 40% (n = 331)
      of 833 participants and was 1.7 and 1.8 times more likely in international and
      provincial/inter-county athletes compared to those who were recreationally active
      (International: odds ratios (OR) 1.68, 95% confidence intervals (95%CI) 1.12
      2.54; Provincial/inter-county: OR 1.83, 95%CI 1.20-2.77). In participants at risk
      of LEA, missing >22 days of training during the previous year due to illness
      occurred 3 times more frequently (OR 3.01, 95%CI 1.81-5.02). CONCLUSION: Risk of
      LEA was widespread in this heterogeneous sample. Awareness of LEA and the
      development of appropriate energy management strategies to ensure athlete health
      across levels of competition are required.

PMID- 30303469
TI  - Improvement of recombinant-truncated Burkholderia motility protein A (BimA)-based
      indirect ELISA for equine glanders.
AB  - Glanders is a contagious and highly fatal disease of equines with zoonotic
      potential. It is caused by a Gram-negative, nonmotile bacterium Burkholderia
      mallei. Complement fixation test (CFT) is one of the most commonly used tests for
      diagnosis of glanders; however, it has some limitations. A recombinant-truncated
      Burkholderia intracellular motility A (BimA) protein-based indirect enzyme-linked
      immunosorbent assay (iELISA) was previously reported by us for glanders
      diagnosis, which has been re-optimized in this study using a panel of glanders
      positive (n = 75) and glanders negative (n = 227) serum samples. The improved
      iELISA exhibited 96% sensitivity and 90.75% specificity. The assay had 98.56%
      negative predictive value. In the improved iELISA, background for negative
      samples was reduced and a rational assay cut-off based on ROC curves was
      introduced. Intra laboratory repeatability of the iELISA was tested by 3
      different operators with 100% correlation. The BimA-coated ELISA plates could be
      used without significant decrease in diagnostic efficacy even after their storage
      at room temperature or 37 degrees C for 90 days. Overall, the improved iELISA is
      a sensitive, specific, reproducible, and easy-to-use assay that has potential in
      serodiagnosis of glanders, more suitably to demonstrate freedom from B. mallei
      infection in a population.

PMID- 30303471
TI  - Industry use of 'better-for-you' features on labels of sugar-containing
      beverages.
AB  - OBJECTIVE: To examine the ways in which sugar-containing beverages are being
      portrayed as 'better-for-you' (BFY) via features on product labels. DESIGN: Cross
      sectional audit of beverage labels. SETTING: Adelaide, Australia. Data on
      beverage labels were collected from seventeen grocery stores during September to
      November 2016. SUBJECTS: The content of 945 sugar-containing beverages labels
      were analysed for explicit and implicit features positioning them as healthy or
      BFY. RESULTS: The mean sugar content of beverages was high at 8.3 g/100 ml and
      most sugar-containing beverages (87.7 %) displayed features that position them as
      BFY. This was most commonly achieved by indicating the beverages are natural
      (76.8 %), or contain reduced or natural energy/sugar content (48.4 %), or through
      suggesting that they contribute to meeting bodily needs for nutrition (28.9 %) or
      health (15.1 %). Features positioning beverages as BFY were more common among
      certain categories of beverages, namely coconut waters, iced teas, sports drinks
      and juices. CONCLUSIONS: A large proportion of sugar-containing beverages use
      features on labels that position them as healthy or BFY despite containing high
      amounts of sugar.

PMID- 30303472
TI  - Streptomyces durbertensis sp. nov., isolated from saline-alkali soil.
AB  - A novel strain of actinobacteria, designated NEAU-S1GS20T, was isolated from a
      saline-alkali soil collected from Heilongjiang Province, north-east China, and
      characterized using a polyphasic approach. Strain NEAU-S1GS20T exhibited
      morphological, cultural and chemotaxonomic features consistent with its
      classification as representing a member of the genus Streptomyces. Growth
      occurred at 18-45  degrees C, at pH 6.0-10.0 and in the presence of 10 % (w/v)
      NaCl. Whole-cell hydrolysates mainly contained glucose and ribose. The
      predominant menaquinones were MK-9(H4) and MK-9(H6). The polar lipids were
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and two
      unidentified phospholipids. The major cellular fatty acids (>10 %) were iso-C16 :
      0, iso-C17 : 0, anteiso-C17 : 0 and C16 : 0. The G+C content of the DNA was 72.8
      mol%. A phylogenetic tree based on 16S rRNA gene sequences showed that strain
      NEAU-S1GS20T formed a distinct clade within the genus Streptomyces and was
      closely related to Streptomyces xinghaiensis CCTCC AA 208049T (98.4 %
      similarity), Streptomyces chumphonensis JCM 18522T (98.1 %) and Streptomyces
      palmae JCM 31289T (98.1 %). Multilocus sequence analysis (MLSA) using five
      housekeeping genes (atpD, gyrB, recA, rpoB and trpB) showed that the MLSA
      distance of strain NEAU-S1GS20T to the most closely related species was greater
      than the 0.007 threshold. A combination of DNA-DNA hybridization results and
      differences in certain phenotypic characteristics demonstrated that strain NEAU
      S1GS20T could be distinguished from its closest phylogenetic relatives.
      Therefore, strain NEAU-S1GS20T represents a novel species of the genus
      Streptomyces, for which the name Streptomyces durbertensis sp. nov. is proposed.
      The type strain is NEAU-S1GS20T (=CCTCC AA 2017006T=DSM 104538T).

PMID- 30303473
TI  - Herbaspirillum piri sp. nov., isolated from bark of a pear tree.
AB  - A Gram-stain-negative, aerobic, motile bacterial strain, shQ-4T, was isolated
      from a pear tree in Henan Province, China. The strain grew at 10-41  degrees C,
      at pH 4.0-8.0 and in the presence of 1-3 % (w/v) NaCl. It shared highest 16S rRNA
      gene sequence similarity (96.66 %) with Herbaspirillum chlorophenolicum CPW301T.
      The phylogenetic tree based on 16S rRNA gene sequences showed that strain shQ-4T
      formed a distinct branch next to reference species in the genus Herbaspirillum.
      The profile of major polar lipids of strain shQ-4T contained
      phosphatidylethanolamine (PE), diphosphatidylglycerol (DPG), phosphatidylglycerol
      (PG) and an unidentified aminophospholipid (APL). The major respiratory quinone
      was Q-8. The major fatty acids of this strain were C16 : 0, summed feature 3 (C16
      : 1omega6c/C16 : 1omega7c), C17 : 0 cyclo and C18 : 0. Strain shQ-4T is
      considered to represent a novel species of the genus Herbaspirillum, with the
      proposed name Herbaspirillum piri sp. nov. The type strain is shQ-4T (=CFCC
      14641T=KCTC 52804T).

PMID- 30303474
TI  - International Committee on Systematics of Prokaryotes Subcommittee on the
      taxonomy of Chlamydiae. Minutes of the closed meeting, 7 September 2016, Oxford,
      UK.

PMID- 30303475
TI  - Ignatzschineria cameli sp. nov., isolated from necrotic foot tissue of
      dromedaries (Camelus dromedarius) and associated maggots (Wohlfahrtia species) in
      Dubai.
AB  - Five bacterial strains, UAE-HKU57T, UAE-HKU58, UAE-HKU59, UAE-HKU60 and UAE
      HKU61, were isolated in Dubai, UAE, from necrotic foot tissue samples of four
      dromedaries (Camelus dromedarius) and associated maggots (Wohrlfartia species).
      They were non-sporulating, Gram-negative, non-motile bacilli. They grew well
      under aerobic conditions at 37  degrees C, but not anaerobically. The pH range
      for growth was pH 7.0-9.0 (optimum, pH 7.5-8.0) and the strains could tolerate
      NaCl concentrations (w/v) up to 2 % (optimum, 0.5 %). They were catalase- and
      cytochrome oxidase-positive, but caseinase-, gelatinase- and urease-negative.
      Their phenotypic characters were distinguishable from other closely related
      species. Phylogenetic analyses of the almost-complete 16S rRNA gene and partial
      23S rRNA gene, gyrB, groEL and recA sequences revealed that the five isolates
      were most closely related to undescribed Ignatzschineria strain F8392 and
      Ignatzschineria indica, but in most phylogenies clustered separately from these
      close relatives. Average nucleotide identity analysis showed that genomes of the
      five isolates (2.47-2.52 Mb, G+C content 41.71-41.86 mol%) were 98.00-99.97%
      similar to each other, but <=87.18 % similar to other
      Ignatzschineriaspecies/strains. Low DNA relatedness between the five isolates to
      other Ignatzschineriaspecies/strains was also supported by Genome-to-Genome
      Distance Calculator analysis. The chemotaxonomic traits of the five strains were
      highly similar. They were non-susceptible (intermediate or resistant) to
      tetracycline and resistant to trimethoprim/sulphamethoxazole. The name
      Ignatzschineria cameli sp. nov. is proposed to accommodate these five strains,
      with strain UAE-HKU57T (=CCOS1165T=NBRC 113042T) as the type strain.

PMID- 30303477
TI  - Streptomyces lichenis sp. nov., isolated from lichen.
AB  - A new actinobacterial strain, LCR6-01T, was isolated from a lichen sample
      collected from Chiang Rai Province, Thailand. Its taxonomic position was
      determined using a polyphasic approach. The strain had morphological
      characteristics and chemotaxonomic properties identical to those of members of
      the genus Streptomyces. The predominant menaquinones were MK-9(H6) and MK-9(H8).
      The major fatty acids were anteiso-C15 : 0, iso-C15 : 0, iso-C16 : 0, iso-C14 : 0
      and C16 : 0. The polar lipids were diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylglycerol, an unidentified
      phosphoglycolipid, an unidentified phospholipid and an unidentified lipid. The
      genomic DNA G+C content was 74.5 mol%. Phylogenetic analysis based on 16S rRNA
      gene sequences suggested that the strain belonged to the genus Streptomyces. The
      strain showed highest 16S rRNA gene sequence similarity to Streptomyces palmae
      TBRC 1999T (98.6 %), Streptomyces misionensis JCM 4497T (98.6 %), Streptomyces
      matensis JCM 4268T (98.5 %), Streptomyces althioticus KCTC 9752T (98.5 %) and
      Streptomyces wuyuanensis KCTC 29112T (98.4 %). DNA-DNA relatedness values among
      the strain and closely related Streptomyces species were below 70 %. On the basis
      of the phenotypic characteristics and genotypic distinctiveness, strain LCR6-01T
      is considered to represent a novel species of the genus Streptomyces, for which
      the name Streptomyces lichenis sp. nov. is proposed. The type strain is LCR6-01T
      (=KCTC 39908T=TISTR 2500T).

PMID- 30303476
TI  - Hanstruepera crassostreae sp. nov., a novel marine bacterium of the family
      Flavobacteriaceae isolated from an oyster.
AB  - A Gram-stain-negative, rod-shaped, non-motile, aerobic and orange-pigmented
      marine bacterium, designated strain L53T, was isolated from an oyster sample
      collected from the coast of Weihai, China (122.0 degrees  E 37.5 degrees  N).
      Growth of strain L53T occurred at 4-40  degrees C (optimum, 33  degrees C), at pH
      6.5-8.0 (optimum, pH 7.5) and with 1.0-7.0 % (w/v) NaCl (optimum, 3.0 %).
      Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain L53T
      was closely related to Bizionia echini KCTC 22015T (96.9 %) and Hanstruepera
      neustonica JCM 19743T (96.1 %). Strain L53T was located in a distinct phyletic
      lineage in a discrete clade associated with H. neustonica JCM 19743T. The DNA G+C
      content of strain L53T was 33.5 mol%. The sole menaquinone was MK-6. The polar
      lipids comprised one phosphatidylethanolamine, four unidentified aminolipids and
      four unidentified lipids. The major fatty acids were iso-C15 : 0, iso-C17 : 0 3
      OH and iso-C15 : 0 G. Based on morphological, physiological and molecular
      properties as well as on phylogenetic distinctiveness, strain L53T should be
      placed in the genus Hanstruepera as representing a novel species, for which the
      name Hanstruepera crassostreae sp. nov. is proposed. The type strain is L53T
      (=KCTC 62247T=MCCC 1H00246T).

PMID- 30303478
TI  - Polymorphic variability in the exon 19 of the RB1 gene and its flanking intronic
      sequences in HPV16-associated precancerous lesions in the Greek population.
AB  - PURPOSE: The tumour suppressor protein RB plays a decisive role in negative
      control of the cell cycle, inhibiting tumour development. The present analysis
      investigated the prevalence of the nucleotide polymorphism A153104G, which is
      located at intron 18 of the RB1 gene, and investigated the impact of the
      polymorphic variability in the exon 19 and its flanking intronic sequences on the
      severity of cervical disease in HPV16-positive Greek women. METHODOLOGY: The
      nucleotide polymorphism A153104G was detected by PCR-RFLP assay, while the
      amplicons were further subjected to cloning and sequencing. Moreover, molecular
      evolutionary analysis was performed using the maximum-likelihood (ML) and
      empirical Bayesian (EB) methods in order to evaluate the selective pressure
      acting on exon 19 of the RB1 gene.Results/Key findings. The A153104G nucleotide
      polymorphism was only detected in one control case. Moreover, sequence analysis
      of the amplicons revealed that the polymorphic variability in the RB1 gene
      increased with the severity of the cervical dysplasia. The link between the
      observed polymorphic variability and the progress of cervical disease was
      reflected in the molecular evolutionary analysis that was performed on the exon
      19 of the RB1 gene, since negative selective pressure was acting upon exon 19 in
      the control and low-grade squamous intraepithelial lesion (LSIL) cervical
      samples, while positive selective pressure was acting upon exon 19 in the high
      grade squamous intraepithelial lesion (HSIL) specimens. CONCLUSIONS: The A153104G
      nucleotide polymorphism did not emerge as a potential biomarker for the
      development of precancerous lesions in the Greek patients, while the accumulation
      of sequence variations in RB1 gene might influence patients' susceptibility
      towards the progression of cervical neoplasia.

PMID- 30303480
TI  - Australian porcine clonal complex 10 (CC10) Escherichia coli belong to multiple
      sublineages of a highly diverse global CC10 phylogeny.
AB  - We recently identified clonal complex 10 (CC10) Escherichia coli as the
      predominant clonal group in two populations of healthy Australian food-production
      pigs. CC10 are highly successful, colonizing humans, food-production animals,
      fresh produce and environmental niches. Furthermore, E. coli within CC10 are
      frequently drug resistant and increasingly reported as human and animal extra
      intestinal pathogens. In order to develop a high-resolution global phylogeny and
      determine the repertoire of antimicrobial-resistance genes, virulence-associated
      genes and plasmid types within this clonal group, we downloaded 228 publicly
      available CC10 short-read genome sequences for comparison with 20 porcine CC10 we
      have previously described. Core genome single nucleotide polymorphism phylogeny
      revealed a highly diverse global phylogeny consisting of multiple lineages that
      did not cluster by geography or source of the isolates. Australian porcine
      strains belonged to several of these divergent lineages, indicative that CC10 is
      present in these animals due to multiple colonization events. Differences in
      resistance gene and plasmid carriage between porcine strains and the global
      collection highlighted the role of lateral gene transfer in the evolution of CC10
      strains. Virulence profiles typical of extra-intestinal pathogenic E. coli were
      present in both Australian porcine strains and the broader collection. As both
      the core phylogeny and accessory gene characteristics appeared unrelated to the
      geography or source of the isolates, it is likely that the global expansion of
      CC10 is not a recent event and may be associated with faecal carriage in humans.

PMID- 30303479
TI  - Within-host Mycobacterium tuberculosis diversity and its utility for inferences
      of transmission.
AB  - Whole genome sequencing in conjunction with traditional epidemiology has been
      used to reconstruct transmission networks of Mycobacterium tuberculosis during
      outbreaks. Given its low mutation rate, genetic diversity within M. tuberculosis
      outbreaks can be extremely limited - making it difficult to determine precisely
      who transmitted to whom. In addition to consensus SNPs (cSNPs), examining
      heterogeneous alleles (hSNPs) has been proposed to improve resolution. However,
      few studies have examined the potential biases in detecting these hSNPs. Here, we
      analysed genome sequence data from 25 specimens from British Columbia, Canada.
      Specimens were sequenced to a depth of 112-296*. We observed biases in read
      depth, base quality, strand distribution and read placement where possible hSNPs
      were initially identified, so we applied conservative filters to reduce false
      positives. Overall, there was phylogenetic concordance between the observed 2542
      cSNP and 63 hSNP loci. Furthermore, we identified hSNPs shared exclusively by
      epidemiologically linked patients, supporting their use in transmission
      inferences. We conclude that hSNPs may add resolution to transmission networks,
      particularly where the overall genetic diversity is low.

PMID- 30303481
TI  - Development of a rapid colorimetric multiplex PCR-reverse line blot for the
      detection and typing of 14 Chlamydia trachomatis genovars.
AB  - PURPOSE: Chlamydia trachomatis is responsible for trachoma-associated blindness
      as well as the most common sexually transmitted bacterial infection worldwide,
      although the genovars for the former are typically A-C, whilst for the latter
      they are D-K and for the uncommon infection lymphogranuloma venereum they are L1
      3. Nucleotide variations within the ompA gene facilitate the identification of C.
      trachomatis genovars. This study describes a colorimetric multiplex PCR/RLB
      typing assay (mPCR-RLB) directed to the VD2 region of the ompA gene for general
      C. trachomatis positivity and the identification of 14 individual C. trachomatis
      genovars. METHODOLOGY: The assay was validated by analysing 40 blinded samples
      that included reference strains of C. trachomatis genovars and other non
      chlamydial micro-organisms that had been analysed previously using quantitative
      PCR (qPCR). Ninety clinical samples that had previously been found to be C.
      trachomatis-positive by qPCR were also evaluated using the mPCR-RLB assay.
      RESULTS: The mPCR-RLB assay showed 100 % agreement with the qPCR in the detection
      of C. trachomatis reference strains and no cross-reaction of non-chlamydial micro
      organisms was observed. In the analysis of the chlamydial clinical samples, 97.8
      % were C. trachomatis-positive by mPCR/RLB assay and there was a 96.6 %
      concordance with the qPCR at the group identification level and a 92.2 %
      concordance at the genovar level. CONCLUSION: The mPCR-RLB assay is a rapid and
      sensitive methodology for the identification of C. trachomatis genovars
      associated with urogenital infections, trachoma or lymphogranuloma venereum
      diseases that can be implemented in clinical settings, helping to identify
      reinfections and treatment failures and establish the appropriate treatment
      course.

PMID- 30303483
TI  - Correction: Two single-point mutations shift the ligand selectivity of a
      pheromone receptor between two closely related moth species.

PMID- 30303485
TI  - Examination of diabetes management apps recommended from a Google search: Dr
      Google, which app should I use?
AB  - BACKGROUND: The availability of smartphone health apps empowers people to engage
      in self-care. There are currently over 300,000 health apps available on the
      market targeting a variety of user needs from weight loss to management of
      chronic conditions, with diabetes being the most commonly targeted condition. To
      date, health apps largely fall outside government regulation, and there are no
      official guidelines to help clinicians and patients in app selection. Patients
      commonly resort to the internet for suggestions on which diabetes app to use.
      OBJECTIVE: To investigate apps identified through a Google search and
      characterize these apps in terms of features which support diabetes management.
      METHODS: We performed a Google search for the "best diabetes apps 2017", and
      explored the first four search results. We identified and compiled a list of the
      apps recommended in the returned search results, which were web articles.
      Information about each app was extracted from the articles and corresponding app
      store descriptions. We examined the apps for the following diabetes management
      features: medication management, blood glucose self-management, physical
      activity, diet/nutrition and weight management. RESULTS: Twenty-six apps were
      recommended from four articles. One app was listed in all four articles, and
      three apps appeared on three of the four lists. Apart from one article, there
      were no explicit criteria to justify or explain the selection of apps. We found
      wide variation in the type and the number of diabetes management features in the
      recommended apps. Five apps required payment in order to be used. Two-thirds of
      the apps have blood glucose management features, and less than half have
      medication management features. The most prevalent app features were
      nutrition/diet-related (79%) and physical activity tracking (58%). CONCLUSIONS:
      The ambiguity of app selection and the wide variability in key features of the
      apps recommended for diabetes management makes it difficult for patients to
      select the most appropriate app. It is critical to involve clinicians, relevant
      professional bodies and policymakers to define the key features an app should
      have for it to be classified as a "diabetes management" app. The lessons learned
      here should be taken into account when recommending and developing apps for other
      chronic conditions.

PMID- 30303482
TI  - Context-enriched interactome powered by proteomics helps the identification of
      novel regulators of macrophage activation.
AB  - The role of pro-inflammatory macrophage activation in cardiovascular disease
      (CVD) is a complex one amenable to network approaches. While an indispensible
      tool for elucidating the molecular underpinnings of complex diseases including
      CVD, the interactome is limited in its utility as it is not specific to any cell
      type, experimental condition or disease state. We introduced context-specificity
      to the interactome by combining it with co-abundance networks derived from
      unbiased proteomics measurements from activated macrophage-like cells. Each
      macrophage phenotype contributed to certain regions of the interactome. Using a
      network proximity-based prioritization method on the combined network, we
      predicted potential regulators of macrophage activation. Prediction performance
      significantly increased with the addition of co-abundance edges, and the
      prioritized candidates captured inflammation, immunity and CVD signatures.
      Integrating the novel network topology with transcriptomics and proteomics
      revealed top candidate drivers of inflammation. In vitro loss-of-function
      experiments demonstrated the regulatory role of these proteins in pro
      inflammatory signaling.

PMID- 30303487
TI  - Double coronary lumen: optical coherence tomography findings.

PMID- 30303486
TI  - The Relationship Between Acceptance Intention Toward a Smartphone Healthcare
      Application and Health-Promoting Behaviors Among Nursing Students.
AB  - The purpose of this study was to identify the relationship between acceptance
      intention toward a smartphone healthcare application and health-promoting
      behaviors among nursing students in order to propose a method to encourage
      nursing students' personal health management. Data were collected from June to
      July 2015 in two cities located in South Korea, targeting 450 nursing students.
      There was a weak positive relationship between acceptance intention toward a
      smartphone healthcare application and health-promoting behaviors (r = 0.281, P <
      .001). There were differences in health-promoting behaviors according to the
      level of acceptance intention toward a smartphone healthcare application: health
      promoting behavior scores for the upper 50% of participants with higher intention
      scores (high-score group) were statistically higher than those for the lower 50%
      of participants (low-score group) (t = 4.247, P < .001). In the logistic
      regression, the high-score group had a greater likelihood of performing health
      promoting behaviors (odds ratio, 2.260; P < .001, 95% confidence interval, 1.539
      3.321). Health-promoting behaviors tended to increase among nursing students when
      the acceptance intention toward a smartphone healthcare application was high. To
      increase nursing students' intention to accept a smartphone healthcare
      application, it is necessary to develop applications featuring diverse,
      interesting health-related content suitable for their needs, so that they want to
      use these applications to promote health.

PMID- 30303484
TI  - Ongoing, rational calibration of reward-driven perceptual biases.
AB  - Decision-making is often interpreted in terms of normative computations that
      maximize a particular reward function for stable, average behaviors. Aberrations
      from the reward-maximizing solutions, either across subjects or across different
      sessions for the same subject, are often interpreted as reflecting poor learning
      or physical limitations. Here we show that such aberrations may instead reflect
      the involvement of additional satisficing and heuristic principles. For an
      asymmetric-reward perceptual decision-making task, three monkeys produced
      adaptive biases in response to changes in reward asymmetries and perceptual
      sensitivity. Their choices and response times were consistent with a normative
      accumulate-to-bound process. However, their context-dependent adjustments to this
      process deviated slightly but systematically from the reward-maximizing
      solutions. These adjustments were instead consistent with a rational process to
      find satisficing solutions based on the gradient of each monkey's reward-rate
      function. These results suggest new dimensions for assessing the rational and
      idiosyncratic aspects of flexible decision-making.

PMID- 30303489
TI  - Plasma YKL-40 levels correlate with the severity of coronary atherosclerosis
      assessed with the SYNTAX score.
AB  - Introduction YKL-40 is a protein released locally by inflammatory cells. Thus, it
      may constitute a biomarker of inflammatory conditions, such as atherosclerosis.
      Objectives The aim of the study was to determine YKL-40 levels in patients with
      ischemic heart disease and to analyze the correlation of this biomarker with the
      severity of coronary atherosclerosis. Patients and methods The study included 158
      patients: 52 with stable ischemic heart disease and 67 with acute coronary
      syndrome: ST-segment elevation myocardial infarction (STEMI; n = 47) or non-ST
      segment elevation myocardial infarction (NSTEMI; n = 20). The control group
      included 39 individuals without abnormalities in coronary vessels. We evaluated
      plasma YKL-40 levels and their correlation with the severity of coronary
      atherosclerosis assessed with the SYNTAX score. Results Patients with myocardial
      infarction had higher plasma YKL-40 levels than those with stable ischemic
      disease (median [range], 235.3 [161.6-366.1] ng/ml vs 61.2 [53.1-83.1] ng/ml; P
      <0.001) or controls (median [range], 235.3 [161.6-366.1] ng/ml vs 55.7 [51.2
      75.2] ng/ml; P <0.001). No differences were found in YKL-40 concentrations
      between STEMI and NSTEMI patients (median [range], 263 [150.3-363.7] ng/ml and
      214.9 [163.4-367.6] ng/ml, respectively; P = 0.7). The SYNTAX score in patients
      with ischemic heart disease correlated positively with YKL-40 concentrations (R =
      0.34; P <0.001). Conclusions YKL-40 can be considered a potential biomarker of
      coronary atherosclerosis severity.

PMID- 30303490
TI  - Symptoms of chronic bronchitis in individuals without chronic obstructive
      pulmonary disease: prevalence, burden, and risk factors in southern Poland.
AB  - Introduction Chronic bronchitis (CB) symptoms are commonly reported in
      individuals without chronic obstructive pulmonary disease (COPD), but CB is
      rarely diagnosed in this population. Objectives We aimed to determine the
      prevalence and burden of CB, as well as its risk factors, in a population of
      patients without COPD. Patients and methods Data from the "Health Action" program
      (a lung cancer prevention and health care improvement program conducted in
      Proszowice County, Poland) were used. All county inhabitants aged 40 years or
      older without COPD were invited to participate. As part of the program, a
      questionnaire was administered to assess CB symptoms and risk factors. Spirometry
      at baseline and after the bronchodilator test was also performed. Results CB
      symptoms were present in 9.1% of the 3558 participants. The prevalence of CB in
      the study population was 7.12% (95% CI, 6.70-7.56). Patients with CB had more
      dyspnea and more often received medical treatment for lung disease or were
      hospitalized for respiratory disorders than patients without CB. CB was
      associated with worse lung function and a worse score in the modified Medical
      Research Council Dyspnea Scale even after adjustment for possible confounders. In
      a multivariate analysis, male sex, age over 70 years, current smoking, passive
      exposure to tobacco smoke, gas or wood heating, occupational exposure to chemical
      agents, lower forced expiratory volume in 1 second, and asthma correlated with an
      increased risk of CB. Conclusions CB symptoms are common in individuals without
      COPD aged 40 years or older and are associated with more dyspnea irrespective of
      lung function and comorbidities.

PMID- 30303488
TI  - Development of a novel aortic dissection mouse model and evaluation of drug
      efficacy using in-vivo assays and database analyses.
AB  - OBJECTIVE: Aortic dissection is a life-threatening disease. At present, the only
      therapeutic strategies available are surgery and antihypertensive drugs.
      Moreover, the molecular mechanisms underlying the onset of aortic dissection are
      still unclear. We established a novel aortic dissection model in mice using
      pharmacologically induced endothelial dysfunction. We then used the Japanese
      Adverse Drug Event Report database to investigate the role of pitavastatin in
      preventing the onset of aortic dissection. METHODS AND RESULTS: To induce
      endothelial dysfunction, Nomega-nitro-L-arginine methyl ester, a nitric oxide
      synthase inhibitor, was administered to C57BL/6 mice. Three weeks later,
      angiotensin II (Ang II) and beta-aminopropionitrile (BAPN), a lysyl oxidase
      inhibitor, were administered with osmotic mini-pumps. False lumen formation was
      used as the pathological determinant of aortic dissection. The incidences of
      aortic dissection and death from aneurysmal rupture were significantly higher in
      the Nomega-nitro-L-arginine methyl ester, Ang II, and BAPN (LAB) group than they
      were in the Ang II and BAPN (AB) group.Pitavastatin was administered orally to
      LAB mice. It significantly lowered the incidences of dissection and rupture. It
      also decreased inflammation and medial degradation, both of which were
      exacerbated in the LAB group. The Japanese Adverse Drug Event Report database
      analysis indicated that there were 113 cases of aortic dissection out of 95 090
      patients (0.12%) not receiving statins but only six cases out of 16 668 patients
      receiving statins (0.04%) (odds ratio: 0.30; P = 0.0043). CONCLUSION: Our results
      suggest that endothelial dysfunction is associated with the onset of aortic
      dissection and pitavastatin can help prevent this condition.

PMID- 30303491
TI  - Effect of beta-blockers on 1-year survival and hospitalizations in patients with
      heart failure and atrial fibrillation: results from ESC-HF Pilot and ESC-HF Long
      Term Registry.
AB  - Introduction The positive effect of beta-blocker therapy in patients with heart
      failure (HF) and atrial fibrillation (AF) has been questioned. Objectives We
      aimed to assess the effect of beta-blockers and heart rate (HR) control on 1-year
      outcomes in patients with HF and AF. Patients and methods Of the 2019 Polish
      patients enrolled in ESC-HF Pilot and ESC-HF Long-Term Registry, 797 patients
      with HF and AF were classified into 2 groups depending on beta-blocker use.
      Additionally, patient survival was compared between 3 groups classified according
      to HR: lower than 80 bpm, between 80 and 109 bpm, and of 110 bpm or higher. The
      primary endpoint was all-cause death and the secondary endpoint was all-cause
      death or HF hospitalization. Results In patients treated with beta-blockers, the
      primary and secondary endpoints were less frequent than in patients not using
      beta-blockers (10.9% vs 25.6%, P = 0.001 and 30.6% vs 44.2%, P = 0.02,
      respectively). Absence of beta-blocker treatment was a predictor of both
      endpoints in a univariate analysis but remained an independent predictor only of
      the primary endpoint in a multivariate analysis (hazard ratio for beta-blocker
      use, 0.52; 95% CI, 0.31-0.89; P = 0.02). The primary and secondary endpoints were
      more frequent in patients with a HR of 110 bpm or higher, but the HR itself did
      not predict the study endpoints in the univariate analysis. Conclusions beta
      blocker use might decrease mortality in patients with HF and AF, but it seems to
      have no impact on the risk of HF hospitalization. An HR of 110 bpm or higher may
      be related to worse survival in these patients.

PMID- 30303492
TI  - Plazomicin for the treatment of patients with complicated urinary tract
      infection.
AB  - In June 2018, the United States Food and Drug Administration (FDA) approved
      plazomicin, a novel neoglycoside, for the treatment of adults with complicated
      urinary tract infections who have limited or no alternative treatment options.
      This approval was based on substantial preclinical and clinical work, and marks
      an important advance in the treatment of multidrug-resistant bacterial pathogens.
      This manuscript reviews the in vivo and in vitro work that led to the approval of
      plazomicin and examines how the drug may be used in the years ahead to treat
      patients with aggressive and life-threatening infections.

PMID- 30303493
TI  - An update on tolvaptan for autosomal dominant polycystic kidney disease.
AB  - Tolvaptan is an orally active antagonist of vasopressin (antidiuretic hormone
      [ADH]) V2 receptors. By blocking water reabsorption in kidney collecting ducts,
      it prompts renal free-water excretion and has been used for the treatment of
      hyponatremia, both euvolemic due to the syndrome of inappropriate ADH secretion,
      and hypervolemic due to liver cirrhosis and congestive heart failure. In the past
      few years, it has been shown that vasopressin and its second messenger cyclic
      adenosine monophosphate (cAMP) play an important role in the pathogenesis of
      autosomal dominant polycystic kidney disease (ADPKD). This has been the rationale
      for the use of tolvaptan to halt the progression of ADPKD, mainly through slowing
      kidney growth and decline in renal function. Two major randomized clinical trials
      have demonstrated the benefits of tolvaptan in slowing the progression of ADPKD
      in terms of kidney growth and decline in renal function at 1 and 3 years (REPRISE
      and TEMPO). However, the long-term effectiveness of treatment with tolvaptan
      remains to be determined.

PMID- 30303494
TI  - Update on multikinase inhibitor therapy for differentiated thyroid cancer.
AB  - Curative therapies for radioiodine-refractory differentiated thyroid cancer
      remain lacking. However, oral multikinase inhibitors often allow for disease
      control and improved progression-free survival. Two agents, lenvatinib and
      sorafenib, have been approved for radioiodine-refractory differentiated thyroid
      cancer on the basis of phase III clinical trials showing marked response rates
      and improved progression-free survival over placebo. Several other multikinase
      inhibitors, including apatinib, axitinib, cabozantinib, pazopanib, sunitinib and
      vandetanib, have also been studied in phase II clinical trials, with varying
      response rates and comparable progression-free survival. Selective kinase
      inhibitors, including dabrafenib, vemurafenib, selumetinib and gefitinib, offer a
      more targeted approach and have also been studied in phase II clinical trials.
      While the emergence of these treatments has changed the landscape of management
      of advanced thyroid cancer, clinical challenges remain, and there are many areas
      of ongoing research.

PMID- 30303495
TI  - Cardiovascular effects of antidiabetic drugs.
AB  - Type 2 diabetes mellitus is a common and severe chronic metabolic disease, which
      confers increased risk of cardiovascular disease and mortality. During the last
      decade a large number of new drugs within the classes dipeptidyl peptidase 4 (DPP
      4) inhibitors (DPP-4Is), glucagon-like peptide 1 (GLP-1) receptor agonists (GLP
      1RAs) and sodium/glucose cotransporter 2 (SGLT-2) inhibitors (SGLT-2Is) have been
      developed and tested in nine large-scale cardiovascular outcome trials (CVOTs).
      Here we review the evidence behind antihyperglycemic treatment of patients with
      type 2 diabetes with a particular focus on compiling and summarizing the evidence
      of hard clinical endpoints stemming from these large CVOTs.

PMID- 30303496
TI  - Renal complications of cancer therapies.
AB  - Cancer patients often exhibit preexisting renal impairment and are simultaneously
      at risk for developing further kidney injury due to direct or indirect
      complications of oncological therapies. The nature of kidney injury is highly
      dependent on the therapy regimen used, and the spectrum of possible kidney
      stressors has widened as a result of the development of new therapeutic
      modalities such as molecular therapy or immunotherapy. Indirect renal
      complications are often due to volume depletion or other therapy-related side
      effects. Direct toxicity from "classic" chemotherapy treatments such as cisplatin
      usually leads to acute tubular necrosis, whereas treatment with protein kinase
      inhibitors is more likely to cause disorders such as thrombotic microangiopathy.
      Immunotherapy often affects kidneys through the development of acute interstitial
      nephritis. Because of the high risk of nephrological complications in oncological
      patients, close monitoring of renal function and the early involvement of a
      nephrologist are strongly recommended.

PMID- 30303497
TI  - On the influence of the titanium source on the composition and structure of novel
      titanoniobates.
AB  - Systematic variation of the titanium source and the reaction temperature applied
      during hydrothermal synthesis led to crystallization of four new titanoniobates:
      {[Ni(cyclam)]4[Ti2Nb8O28]}n.~28nH2O (I), K[Ni(cyclam)]3[TiNb9O28].xH2O; x = 18
      (II), x = 14 (III) and x ~ 10 (IV). These are the first titanoniobates with Ni2+
      centered amine complexes acting as counter cations and additionally, this is the
      first report of transition metal complexes expanded by monotitanoniobates. While
      I is obtained using Ti(OiPr)4, II-IV are formed using K2TiO(C2O4).2H2O as the
      educt. The presence of oxalate anions seems to influence the coordination
      environments of the Ni2+ cations that are octahedrally coordinated in I, and in a
      square-planar environment in II-IV. The titanium source also affects the degree
      of substitution of NbV by TiIV. Temperature-dependent syntheses demonstrate that
      the formation of I does not depend on the reaction temperature, while the
      formation of II-IV is clearly affected by this parameter. Regarding the
      arrangement of crystal water molecules, patterns of different dimensionalities
      ranging from 0D to 3D are formed which can be classified as water clusters. Each
      compound exhibits a pronounced plateau in the thermogravimetric curves after the
      removal of crystal H2O molecules. Rehydration experiments after water removal
      proved that except for compound III, the re-integration of water was successful.

PMID- 30303498
TI  - Synthesis, cytotoxic activity and DNA interaction studies of new dinuclear
      platinum(ii) complexes with an aromatic 1,5-naphthyridine bridging ligand: DNA
      binding mode of polynuclear platinum(ii) complexes in relation to the complex
      structure.
AB  - The synthesis, spectroscopic characterization, cytotoxic activity and DNA binding
      evaluation of seven new dinuclear platinum(ii) complexes Pt1-Pt7, with the
      general formula [{Pt(L)Cl}2(MU-1,5-nphe)](ClO4)2 (1,5-nphe is 1,5-naphthyridine;
      while L is two ammines (Pt1) or one bidentate coordinated diamine:
      ethylenediamine (Pt2), (+/-)-1,2-propylenediamine (Pt3), trans-(+/-)-1,2
      diaminocyclohexane (Pt4), 1,3-propylenediamine (Pt5), 2,2-dimethyl-1,3
      propylenediamine (Pt6), and 1,3-pentanediamine (Pt7)), were reported. In vitro
      cytotoxic activity of these complexes was evaluated against three tumor cell
      lines, murine colon carcinoma (CT26), murine mammary carcinoma (4T1) and murine
      lung cancer (LLC1) and two normal cell lines, murine mesenchymal stem cells (MSC)
      and human fibroblast (MRC-5) cells. The results of the MTT assay indicate that
      all investigated complexes have almost no cytotoxic effects on 4T1 and very low
      cytotoxicity toward LLC1 cell lines. In contrast to the effects on LLC1 and 4T1
      cells, complexes Pt1 and Pt2 had significant cytotoxic activity toward CT26
      cells. Complex Pt1 had a much lower IC50 value for activity on CT26 cells
      compared with cisplatin. In comparison with cisplatin, all dinuclear Pt1-Pt7
      complexes showed lower cytotoxicity toward normal MSC and MRC-5 cells. In order
      to measure the amount of platinum(ii) complexes taken up by the cells, we
      quantified the cellular platinum content using inductively coupled plasma mass
      spectrometry (ICP-QMS). Molecular docking studies performed to evaluate the
      potential binding mode of dinuclear platinum(ii) complexes Pt1-Pt7 and their aqua
      derivatives W1-W7, respectively, at the double stranded DNA showed that groove
      spanning and backbone tracking are the most stable binding modes.

PMID- 30303499
TI  - Enhancement of optical resolution in three-dimensional refractive-index tomograms
      of biological samples by employing micromirror-embedded coverslips.
AB  - Optical diffraction tomography (ODT) enables the reconstruction of the three
      dimensional (3D) refractive-index (RI) distribution of a biological cell, which
      provides invaluable information for cellular and subcellular structures in a non
      invasive manner. However, ODT suffers from an inferior axial resolution, due to
      the limited accessible angles imposed by the numerical aperture of the objective
      lens. In this study, we propose and experimentally demonstrate an approach to
      enhance the 3D reconstruction performance in ODT. By employing trapezoidal
      micromirrors, side scattered signals from the sample are measured for various
      side plane-wave-illumination angles. By combining the side scattered fields with
      the forward scattered fields, the axial resolution and 3D image quality of ODT
      are improved, without changing optical instruments. The feasibility and
      applicability of the proposed method are demonstrated by reconstructing the 3D RI
      distribution of a red blood cell and HeLa cells in hydrogel. We also present
      systematic analyses of the improved 3D imaging performance using numerical
      simulations and experimental measurements for the 3D transfer function, a point
      object, and a microsphere. The analyses demonstrate an improved axial resolution
      of 0.31 MUm, 4.8 times smaller than that of the conventional method. The proposed
      method enables the non-invasive and accurate 3D imaging of 3D cultured cells,
      which is crucial for cell biology studies.

PMID- 30303500
TI  - A potent, minimally invasive and simple strategy of enhancing intracellular
      targeted delivery of Tat peptide-conjugated quantum dots: organic solvent-based
      permeation enhancer.
AB  - Targeted delivery of nanomaterials to specific intracellular locations is
      essential for the development of many nanomaterials-based biological
      applications. Thus far the targeting performance has been limited due to various
      intracellular transport barriers, especially intracellular vesicle trapping. Here
      we report the application of permeation enhancers based on organic solvents in
      small percentage to enhance the intracellular targeted delivery of nanomaterials.
      Previously permeation enhancers based on organic solvents and ionic liquids have
      been used in overcoming biological transport barriers at tissue, organ, and
      cellular levels, but this strategy has so far rarely been examined for its
      potential in facilitating transport of nanometer-scale entities across
      intracellular barriers, particularly intracellular vesicle trapping. Using the
      cell nucleus as a model intracellular target and Tat peptide-conjugated quantum
      dots (QDs-Tat) as a model nanomaterial-based probe, we demonstrate that a small
      percentage (e.g. 1%) of organic solvent greatly enhances nucleus targeting
      specificity as well as increasing endocytosis-based cellular uptake of QDs. We
      combine vesicle colocalization (DiO dye staining), vesicle integrity (calcein dye
      release), and single-particle studies (pair-correlation function microscopy) to
      investigate the process of organic solvent-enhanced vesicle escape of QDs-Tat.
      The organic solvent based vesicle escape-enhancing approach is found to be not
      only very effective but minimally invasive, resulting in high vesicle escape
      efficiency with no significant disruption to the membrane integrity of either
      intracellular vesicles or cells. This approach drastically outperforms the
      commonly used vesicle escape-enhancing agent (i.e., chloroquine, whose
      enhancement effect is based on disrupting vesicle integrity) in both potency and
      minimal invasiveness. Finally, we apply organic solvent-based targeting
      enhancement to improve the intracellular delivery of the anticancer drug
      doxorubicin (DOX).

PMID- 30303502
TI  - Monitoring individual cell-signaling activity using combined metal-clad waveguide
      and surface-enhanced fluorescence imaging.
AB  - Evanescent field based biosensing systems such as surface plasmon resonance
      (SPR), diffraction gratings, or metal-clad waveguides (MCWGs) are powerful tools
      for label-free real-time monitoring of signaling activity of living cells exposed
      to hormones, pharmacological agents, and toxins. In particular, MCWG-based
      imaging is well suited for studying relatively thick objects such as cells due to
      its greater depth of penetration into the sensing medium, compared to SPR. Label
      free methods, however, provide only indirect measurements in that the measured
      signal arises from local changes in material properties rather than from specific
      biomolecular targets. In the case of cells, the situation is especially complex
      as the measured label-free signal may result from a combination of very diverse
      sources: morphological changes, intra-cellular reorganization, cascaded molecular
      events, protein expression etc. Consequently, deconvolving the contributions of
      specific sources to a particular cell response profile can be challenging. In the
      following, we present a cell imaging platform that combines two distinct sensing
      modalities, namely label-free MCWG imaging and label-based surface enhanced
      fluorescence (SEF), designed to facilitate the identification of the underlying
      molecular and structural contributions to the label-free MCWG images. We
      demonstrate the bimodal capabilities of this imaging platform in experiments
      designed to visualize actin cytoskeleton organization in vascular smooth muscle
      cells. We then monitored the real-time response of HEK293 cells expressing the
      Angiotensin 1 receptor (AT1R), when stimulated by the receptor agonist
      Angiotensin II (AngII). The analysis of the simultaneous label-free signal
      obtained by MCWG and the intracellular calcium signal resulting form AT1R
      activation, measured by SEF, allows relating label-free signal features to
      specific markers of receptor activation. Our results show that the intracellular
      calcium levels normally observed following AT1R activation are not required for
      the initial burst of cellular activity observed in the MCWG signal but rather
      indicates signaling activity involving the intracellular kinase ROCK.

PMID- 30303501
TI  - Quantification of hyperpolarisation efficiency in SABRE and SABRE-Relay enhanced
      NMR spectroscopy.
AB  - para-Hydrogen (p-H2) induced polarisation (PHIP) is an increasingly popular
      method for sensitivity enhancement in NMR spectroscopy. Its growing popularity is
      due in part to the introduction of the signal amplification by reversible
      exchange (SABRE) method that generates renewable hyperpolarisation in target
      analytes in seconds. A key benefit of PHIP and SABRE is that p-H2 can be
      relatively easily and cheaply produced, with costs increasing with the desired
      level of p-H2 purity. In this work, the efficiency of the SABRE polarisation
      transfer is explored by measuring the level of analyte hyperpolarisation as a
      function of the level of p-H2 enrichment. A linear relationship was found between
      p-H2 enrichment and analyte 1H hyperpolarisation for a range of molecules,
      polarisation transfer catalysts, NMR detection fields and for both the SABRE and
      SABRE-Relay transfer mechanisms over the range 29-99% p-H2 purity. The gradient
      of these linear relationships were related to a simple theoretical model to
      define an overall efficiency parameter, E, that quantifies the net fraction of
      the available p-H2 polarisation that is transferred to the target analyte. We
      find that the efficiency of SABRE is independent of the NMR detection field and
      exceeds E = 20% for methyl-4,6-d2-nicotinate when using a previously optimised
      catalyst system. For the SABRE-Relay transfer mechanism, efficiencies of up to E
      = 1% were found for 1H polarisation of 1-propanol, when ammonia was used as the
      polarisation carrier.

PMID- 30303503
TI  - Chemically driven surface effects in polar intermetallic topological insulators
      A3Bi.
AB  - Surface electronic spectra, surface and bulk properties as well as the underlying
      chemical bonding characteristics in topological insulators with complex bonding
      patterns are considered for the example of cubic, polar intermetallics KNa2Bi,
      K3Bi and Rb3Bi (with the general formula A3Bi, A - alkali metal). Chemical
      bonding in A3Bi has a delocalized, polar character as elucidated by the Bader
      charge analysis in bulk and at the surface, by real-space bonding indicators and
      by the maximally localized-Wannier-function technique. We underpin emergent
      surface features in the electronic spectra that are driven by chemical bonding.
      The organization of these trivial and topological surface states is juxtaposed
      with the trends in the Bader charges at the surface and surface contributions to
      the on-site matrix elements of the ab initio Hamiltonian in the localized basis.
      The surface states are essentially affected by a large positive or negative on
      site contribution induced near the vacuum boundary, where the sign of the
      contribution depends on the surface termination. Based on our findings, the
      experimentally observed surface features in the related Na3Bi compound can be
      correctly interpreted. The listed aspects distinguish the title compounds from
      the HgX (X - chalcogen) series with the same fingerprint bulk-band dispersion
      near the Fermi level and similar symmetries, but with covalent bonding character.
      Surface effects investigated for A3Bi also can be expected for a wide range of
      compounds of various topological classes with a similar bonding type, and will
      define their surface reactivity.

PMID- 30303504
TI  - Fiber nanogratings induced by femtosecond pulse laser direct writing for in-line
      polarizer.
AB  - Self-organized fiber nanogratings (FNGs) induced by femtosecond pulse laser
      direct writing are demonstrated in optical silica fibers for the first time. Ge
      doping in the silica fiber core plays an important role in the formation of
      nanogratings. Negative changes in refractive index with sawtooth fluctuation and
      strong birefringence of FNGs were investigated by an optical fiber refractive
      index analyzer and a crossed polarization microscope, respectively. The
      polarization features of FNGs were characterized by the Mueller matrix analytical
      method and in-line polarizers based on FNGs were fabricated. FNGs are promising
      integrated components because of their prominent properties of polarization and
      salient compatibility with most fiber-optic systems.

PMID- 30303505
TI  - Zinc finger domains as therapeutic targets for metal-based compounds - an update.
AB  - Zinc finger proteins are one of the most abundant families of proteins and
      present a wide range of structures and functions. The structural zinc ion
      provides the correct conformation to specifically recognize DNA, RNA and protein
      sequences. Zinc fingers have essential functions in transcription, protein
      degradation, DNA repair, cell migration, and others. Recently, reports on the
      extensive participation of zinc fingers in disease have been published. On the
      other hand, much information remains to be unravelled as many genomes and
      proteomes are being reported. A variety of zinc fingers have been identified;
      however, their functions are still under investigation. Because zinc fingers have
      identified functions in several diseases, they are being increasingly recognized
      as drug targets. The replacement of Zn(ii) by another metal ion in zinc fingers
      is one of the most prominent methods of inhibition. From one side, zinc fingers
      play roles in the toxicity mechanisms of Ni(ii), Hg(ii), Cd(ii) and others. From
      the other side, gold, platinum, cobalt, and selenium complexes are amongst the
      compounds being developed as zinc finger inhibitors for therapy. The main
      challenge in the design of therapeutic zinc finger inhibitors is to achieve
      selectivity. Recently, the design of novel compounds and elucidation of the
      mechanisms of zinc substitution have renewed the possibilities of selective zinc
      finger inhibition by metal complexes. This review aims to update the status of
      novel strategies to selectively target zinc finger domains by metal complexes.

PMID- 30303508
TI  - Facile fabrication of direct solid-state Z-scheme g-C3N4/Fe2O3 heterojunction: a
      cost-effective photocatalyst with high efficiency for the degradation of aqueous
      organic pollutants.
AB  - Graphitic carbon nitride (g-C3N4) is a low cost photocatalyst for the visible
      light-driven degradation of aqueous organic pollutants. Nevertheless, the fast
      recombination of electron-hole pairs significantly inhibits its photocatalytic
      activity. Consequently, we report a novel strategy in which the low cost alpha
      Fe2O3 photocatalyst is in situ introduced to accelerate the photogenerated charge
      separation of g-C3N4 based on a Z-scheme mechanism. Under the irradiation of
      visible light, the photocatalytic activity significantly improved on coupling g
      C3N4 and alpha-Fe2O3, and a peak Rhodamine B (RhB) degradation efficiency of over
      99% were observed. This value is significantly higher than that over pure g-C3N4
      (ca. 67%) and alpha-Fe2O3 (ca. 6%). Additionally, the as-prepared g-C3N4/Fe2O3
      exhibits highly stable photocatalytic activity. The loading of alpha-Fe2O3 on the
      g-C3N4 surface results in the formation of a direct solid-state Z-scheme
      structure. The improved separation of electron-hole pairs and strong redox
      ability of the charge carriers are responsible for the improved photocatalytic
      activity of g-C3N4/Fe2O3. Finally, the h+ and O2- radicals are confirmed as the
      major oxidation species and a possible photocatalytic mechanism is proposed in
      the g-C3N4/Fe2O3 reaction system. This work is of significance to promote the
      large-scale application of g-C3N4-based photocatalysts in water purification.

PMID- 30303509
TI  - Organic sulfur fingerprint indicates continued injection fluid signature 10
      months after hydraulic fracturing.
AB  - Hydraulic fracturing requires the injection of large volumes of fluid to extract
      oil and gas from low permeability unconventional resources (e.g., shale, coalbed
      methane), resulting in the production of large volumes of highly complex and
      variable waste fluids. Shale gas fluid samples were collected from two
      hydraulically fractured wells in Morgantown, WV, USA at the Marcellus Shale
      Energy and Environment Laboratory (MSEEL) and analyzed using ultrahigh resolution
      mass spectrometry to investigate the dissolved organic sulfur (DOS) pool. Using a
      non-targeted approach, ions assigned DOS formulas were analyzed to identify
      dominant DOS classes, describe their temporal trends and their implications, and
      describe the molecular characteristics of the larger DOS pool. The average
      molecular weight of organic sulfur compounds in flowback decreased and was lowest
      in produced waters. The dominant DOS classes were putatively assigned to alcohol
      sulfate and alcohol ethoxysulfate surfactants, likely injected as fracturing
      fluid additives, on the basis of exact mass and homolog distribution matching.
      This DOS signature was identifiable 10 months after the initial injection of
      hydraulic fracturing fluid, and an absence of genes that code for alcohol
      ethoxysulfate degrading proteins (e.g., sulfatases) in the shale well genomes and
      metagenomes support that these additives are not readily degraded biologically
      and may continue to act as a chemical signature of the injected fluid.
      Understanding the diversity, lability, and fate of organic sulfur compounds in
      shale wells is important for engineering productive wells and preventing gas
      souring as well as understanding the consequences of unintended fluid release to
      the environment. The diversity of DOS, particularly more polar compounds, needs
      further investigation to determine if the identified characteristics and temporal
      patterns are unique to the analyzed wells or represent broader patterns found in
      other formations and under other operating conditions.

PMID- 30303512
TI  - A three-dimensional model to study human synovial pathology.
AB  - Therapeutic agents that are used by patients with rheumatic and musculoskeletal
      diseases were originally developed and tested in animal models, and although
      retrospective studies show a limited predictive value, it could be explained by
      the fact that there are no good in vitro alternatives. In this study, we
      developed a 3-dimensional synovial membrane model made of either human primary
      synovial cell suspensions or a mix of primary fibroblast-like synoviocytes and
      CD14+ mononuclear cells. We analyzed the composition of the mature micromasses by
      immunohistochemical staining and flow cytometry and show that the outer surface
      forms a lining layer consisting out of fibroblast-like and macrophage-like cells,
      reflecting the in vivo naive synovial membrane. To recreate the affected synovial
      membrane in rheumatoid arthritis (RA), the micromasses were exposed to the pro
      inflammatory cytokine Tumor Necrosis Factor Alpha (TNF-alpha). This led to
      increased pro-inflammatory cytokine expression and production and to hyperplasia
      of the membrane. To recreate the synovial membrane in osteoarthritis (OA), the
      micromasses were exposed to Transforming Growth Factor Beta (TGF-beta). This led
      to fibrosis-like changes of the membrane, including increased Alpha Smooth Muscle
      Actin and increased expression of fibrosis-related genes PLOD2 and COL1A1.
      Interestingly, the macrophages in the micromass showed phenotypic plasticity as
      prolonged TNF-alpha or TGF-beta stimulation strongly reduced the occurrence of
      Cluster of Differentiation 163-positive M2-like macrophages. We showed the
      plasticity of the micromasses as a synovial model for studying RA and OA
      pathology and propose that the synovial lining micromass system can be a good
      alternative for testing drugs.

PMID- 30303513
TI  - Botulinum toxin testing on animals is still a Europe-wide issue.
AB  - There have been significant developments in the use of animals to test Botulinum
      toxin products in Europe in recent years. This paper summarises and discusses
      these from the perspective of the animal protection organisation. A cell-based
      assay has been validated by Allergan and is now being used for the replacement of
      the mouse bioassay for the batch testing of their Botulinum toxin A products. Two
      further companies (Merz and Ipsen) have recently validated similar cell-based
      assays to replace animals in their batch testing. However, the number of animals
      being used in batch tests across Europe remains at record levels; an estimated
      400,000 animals per year, based on official statistics and non-technical
      summaries. There are concerns from animal protection organisations about the
      authorisation of animal testing for Botulinum toxin products that are to be used
      for aesthetic purposes. Furthermore, should testing for companies that have not
      yet implemented the alternative method continue to be permitted under the EU
      Directive 2010/63 on the use of animals for scientific purposes? Whilst we are on
      the cusp of an era where the mouse bioassay has been replaced for the potency
      testing of Botulinum toxin A for injection, it is important that Europe sees a
      reduction of animal testing in real terms.

PMID- 30303514
TI  - Short half-life of HPV16 E6 and E7 mRNAs sensitizes HPV16-positive tonsillar
      cancer cell line HN26 to DNA-damaging drugs.
AB  - Here we show that treatment of the HPV16-positive tonsillar cancer cell line HN26
      with DNA alkylating cancer drug melphalan-induced p53 and activated apoptosis.
      Melphalan reduced the levels of RNA polymerase II and cellular transcription
      factor Sp1 that were associated with HPV16 DNA. The resulting inhibition of
      transcription caused a rapid loss of the HPV16 early mRNAs encoding E6 and E7 as
      a result of their inherent instability. As a consequence of HPV16 E6 and E7 down
      regulation, the DNA damage inflicted on the cells by melphalan caused induction
      of p53 and activation of apoptosis in the HN26 cells. The BARD1-negative
      phenotype of the HN26 cells may have contributed to the failure to repair DNA
      damage caused by melphalan, as well as to the efficient apoptosis induction.
      Finally, nude mice carrying the HPV16 positive tonsillar cancer cells responded
      better to melphalan than to cisplatin, the chemotherapeutic drug of choice for
      tonsillar cancer. We concluded that the short half-life of the HPV16 E6 and E7
      mRNAs renders HPV16-driven tonsillar cancer cells particularly sensitive to DNA
      damaging agents such as melphalan since melphalan both inhibits transcription and
      causes DNA damage.

PMID- 30303515
TI  - Association between the dietary inflammatory index and all-cause mortality in
      colorectal cancer long-term survivors.
AB  - Pro-inflammatory dietary factors have been shown to be associated with the
      incidence of a range of cancers. However, there are many fewer studies on the
      association between the inflammatory potential of diet and survival after cancer
      diagnosis. We examined the association between post-diagnosis dietary
      inflammatory index (DII(r)) scores and all-cause mortality in long-term survivors
      of colorectal cancer (CRC). DII scores were calculated from dietary data of 1,404
      CRC survivors collected at a median of 6 years after CRC diagnosis. Using
      multivariable-adjusted Cox proportional hazards regression models, hazard ratios
      (HR) and 95% confidence intervals (CI) were estimated for the association of DII
      scores, modeled continuous and in quartiles, with all-cause mortality. After a
      median follow-up time of 7 years (after dietary assessment), 204 study
      participants had died. Overall, in the fully adjusted model there was a
      suggestion of a positive association between DII score and all-cause mortality
      (HRDIIquartile4vs1 : 1.36; 95% CI: 0.88-2.09 and HRDIIcontinuous : 1.08; 95% CI:
      0.97-1.20). However, in subgroup analyses, we found significant differences in
      individuals with metastatic disease (HRDIIcontinuous : 1.34; 95% CI: 1.07-1.67)
      and the absence of stoma (HRDIIcontinuous : 1.15; 95% CI: 1.02-1.29). Overall,
      the post-diagnosis DII was not statistically significantly associated with all
      cause mortality in CRC long-term survivors; however, there was suggestive
      evidence of an association in select subgroups.

PMID- 30303516
TI  - NCI 8628: A randomized phase 2 study of ziv-aflibercept and high-dose interleukin
      2 or high-dose interleukin 2 alone for inoperable stage III or IV melanoma.
AB  - BACKGROUND: Interleukin 2 (IL-2) is a growth factor for T and natural killer
      cells, promotes proinflammatory cytokines, and can lead to durable responses in
      patients with melanoma. Vascular endothelial growth factor (VEGF) promotes
      angiogenesis and modulates host innate and adaptive immunity. High VEGF levels
      were found to be associated with nonresponse to IL-2. Ziv-aflibercept may deplete
      VEGF and thereby enhance antitumor T-cell responses, thus supporting a
      combination immunotherapeutic strategy with IL-2. METHODS: NCI 8628 was a phase 2
      trial of ziv-aflibercept and IL-2 (arm A) versus IL-2 alone (arm B) randomized at
      2:1, respectively. Eligible patients had inoperable American Joint Committee on
      Cancer stage III or stage IV melanoma. The primary endpoint was progression-free
      survival (PFS). RESULTS: A total of 89 patients were enrolled and 84 patients
      were treated. The median follow-up was 41.4 months. Among treated patients (55
      patients in arm A and 29 patients in arm B), PFS was significantly improved in
      favor of arm A, with a median of 6.9 months (95% confidence interval [95% CI],
      4.1-8.7 months) versus 2.3 months (95% CI, 1.6-3.5 months) (P<.001). No
      significant difference was noted with regard to overall survival, with a median
      of 26.9 months (95% CI, 14.4-63.6 months) for arm A and 24.2 months (95% CI, 11.3
      36.4 months) for arm B. The response rate (according to Response Evaluation
      Criteria In Solid Tumors [RECIST]) was 22% in arm A (4 complete responses [CRs]
      and 8 partial responses [PRs]) and 17% in arm B (1 CR and 4 PRs). Stable disease
      or PR or CR was noted in 65% of patients in arm A and 48% of patients in arm B.
      The combination was found to be superior to monotherapy in patients with high and
      low levels of serum VEGF and VEGF receptor 2. Adverse events were consistent with
      the expected profiles of monotherapy with IL-2 and ziv-aflibercept. CONCLUSIONS:
      Ziv-aflibercept and IL-2 were found to significantly improve PFS compared with IL
      2 alone, thereby meeting the primary endpoint of the current study. These
      findings support further study of immunotherapeutic combination strategies
      involving VEGF inhibitors.

PMID- 30303517
TI  - Association of breast cancer risk with polymorphisms in genes involved in the
      metabolism of xenobiotics and interaction with tobacco smoking: a gene-set
      analysis.
AB  - Single nucleotide polymorphisms (SNPs) in genes involved in xenobiotics
      metabolism (XM) are suspected to play a role in breast cancer risk. However,
      previous findings based on a SNP by SNP approach need to be replicated taking
      into account the combined effects of multiple SNPs. We used a gene-set analysis
      method to study the association between breast cancer risk and genetic variation
      in XM genes (seen as a set of SNPs) and in the XM pathway (seen as a set of
      genes). We also studied the interaction between variants in XM genes and tobacco
      smoking. The analysis was conducted in a case-control study of 1125 cases and
      1172 controls. Using a dedicated chip, genotyping data of 585 SNPs in 68 XM genes
      were available. Genetic variation in the whole XM pathway was significantly
      associated with pre-menopausal breast cancer risk (p=0.008). This association was
      mainly driven by genetic variation in NAT2, CYP2C18, CYP2C19, AKR1C2 and ALDH1A3.
      The association between the XM gene pathway and breast cancer was observed among
      current and previous smokers, but not among never smokers (p=0.013 for
      interaction between XM genes and tobacco smoking status). The association with
      breast cancer risk indicates that XM genes variants may play a role in breast
      carcinogenesis through their detoxification function of environmental pollutants,
      such as those contained in tobacco smoke. This article is protected by copyright.
      All rights reserved.

PMID- 30303518
TI  - A blueprint for the primary prevention of cancer: Targeting established,
      modifiable risk factors.
AB  - In the United States, it is estimated that more than 1.7 million people will be
      diagnosed with cancer, and more than 600,000 will die of the disease in 2018. The
      financial costs associated with cancer risk factors and cancer care are enormous.
      To substantially reduce both the number of individuals diagnosed with and dying
      from cancer and the costs associated with cancer each year in the United States,
      government and industry and the public health, medical, and scientific
      communities must work together to develop, invest in, and implement comprehensive
      cancer control goals and strategies at the national level and expand ongoing
      initiatives at the state and local levels. This report is the second in a series
      of articles in this journal that, together, describe trends in cancer rates and
      the scientific evidence on cancer prevention, early detection, treatment, and
      survivorship to inform the identification of priorities for a comprehensive
      cancer control plan. Herein, we focus on existing evidence about established,
      modifiable risk factors for cancer, including prevalence estimates and the cancer
      burden due to each risk factor in the United States, and established primary
      prevention recommendations and interventions to reduce exposure to each risk
      factor.

PMID- 30303519
TI  - Eszopiclone for insomnia.
AB  - BACKGROUND: Insomnia is a major public health issue affecting between 6% to 10%
      of the adult population in Western countries. Eszopiclone is a hypnotic drug
      belonging to a newer group of hypnotic agents, known as new generation hypnotics,
      which was marketed as being just as effective as benzodiazepines for this
      condition, while being safer and having a lower risk for abuse and dependence. It
      is the aim of the review to integrate evidence from randomised controlled trials
      and to draw conclusions on eszopiclone's efficacy and safety profile, while
      taking methodological features and bias risks into consideration. OBJECTIVES: To
      assess the efficacy and safety of eszopiclone for the treatment of insomnia
      compared to placebo or active control. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled trials (CENTRAL), MEDLINE, Embase, PsycINFO,
      PSYNDEX and registry databases (WHO trials portal, ClinicalTrials.gov) with
      results incorporated from searches to 10 February 2016. To identify trials not
      registered in electronic databases, we contacted key informants and searched
      reference lists of identified studies. We ran an update search (21 February 2018)
      and have placed studies of interest in awaiting classification/ongoing studies.
      These will be incorporated into the next version of the review, as appropriate.
      SELECTION CRITERIA: Parallel group randomised controlled trials (RCTs) comparing
      eszopiclone with either placebo or active control were included in the review.
      Participants were adults with insomnia, as diagnosed with a standardised
      diagnostic system, including primary insomnia and comorbid insomnia. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted outcome data; one
      reviewer assessed trial quality and the second author cross-checked it. MAIN
      RESULTS: A total of 14 RCTs, with 4732 participants, were included in this review
      covering short-term (<= 4 weeks; 6 studies), medium-term (> 4 weeks <= 6 months;
      6 studies) and long-term treatment (> 6 months; 2 studies) with eszopiclone. Most
      RCTs included in the review included participants aged between 18 and 64 years,
      three RCTs only included elderly participants (64 to 85 years) and one RCT
      included participants with a broader age range (35 to 85 years). Seven studies
      considered primary insomnia; the remaining studies considered secondary insomnia
      comorbid with depression (2), generalised anxiety (1), back pain (1), Parkinson's
      disease (1), rheumatoid arthritis (1) and menopausal transition (1).Meta-analytic
      integrations of participant-reported data on sleep efficacy outcomes demonstrated
      better results for eszopiclone compared to placebo: a 12-minute decrease of sleep
      onset latency (mean difference (MD) -11.94 min, 95% confidence interval (CI) 
      16.03 to -7.86; 9 studies, 2890 participants, moderate quality evidence), a 17
      minute decrease of wake time after sleep onset (MD -17.02 min, 95% CI -24.89 to 
      9.15; 8 studies, 2295 participants, moderate quality evidence) and a 28-minute
      increase of total sleep time (MD 27.70 min, 95% CI 20.30 to 35.09; 10 studies,
      2965 participants, moderate quality evidence). There were no significant changes
      from baseline to the first three nights after drug discontinuation for sleep
      onset latency (MD 17.00 min, 95% CI -4.29 to 38.29; 1 study, 291 participants,
      low quality evidence) and wake time after sleep onset (MD -6.71 min, 95% CI 
      21.25 to 7.83; 1 study, 291 participants, low quality evidence). Adverse events
      during treatment that were documented more frequently under eszopiclone compared
      to placebo included unpleasant taste (risk difference (RD) 0.18, 95% CI 0.14 to
      0.21; 9 studies, 3787 participants), dry mouth (RD 0.04, 95% CI 0.02 to 0.06; 6
      studies, 2802 participants), somnolence (RD 0.04, 95% CI 0.02 to 0.06; 8 studies,
      3532 participants) and dizziness (RD 0.03, 95% CI 0.01 to 0.05; 7 studies, 2933
      participants). According to the GRADE criteria, evidence was rated as being of
      moderate quality for sleep efficacy outcomes and adverse events and of low
      quality for rebound effects and next-day functioning. AUTHORS' CONCLUSIONS:
      Eszopiclone appears to be an efficient drug with moderate effects on sleep onset
      and maintenance. There was no or little evidence of harm if taken as recommended.
      However, as certain patient subgroups were underrepresented in RCTs included in
      the review, findings might not have displayed the entire spectrum of possible
      adverse events. Further, increased caution is required in elderly individuals
      with cognitive and motor impairments and individuals who are at increased risk of
      using eszopiclone in a non-recommended way.

PMID- 30303521
TI  - To delay or not to delay, that is the question for patients with acute
      lymphoblastic leukemia who do not receive prophylactic cranial irradiation.

PMID- 30303522
TI  - Congestive heart failure in older adults diagnosed with follicular lymphoma: A
      population-based study.
AB  - BACKGROUND: To the authors' knowledge, there is limited information regarding the
      long-term risk of congestive heart failure (CHF) among patients with follicular
      lymphoma, a prevalent non-Hodgkin lymphoma diagnosis among those aged >65 years,
      especially within the context of therapeutic exposures and preexisting
      comorbidities. METHODS: Using Surveillance, Epidemiology, and End Results
      Medicare data from 1999 through 2013, the authors identified 6109 patients with
      follicular lymphoma who were diagnosed at age >=66 years between January 1, 2000
      and December 31, 2011, and a frequency-matched Medicare noncancer sample.
      Subdistribution hazards models assessed risks associated with new-onset CHF
      through December 31, 2013. Propensity score-matched models examined CHF risk in
      patients receiving anthracyclines when compared with matched noncancer controls.
      RESULTS: When compared with matched controls, patients with follicular lymphoma
      receiving anthracyclines at ages 66 to 75 years had a 1.7-fold (95% confidence
      interval, 1.4-fold to 2.1-fold) higher risk of new-onset CHF; patients diagnosed
      at age >75 years did not differ from noncancer controls with regard to CHF risk.
      Preexisting hypertension was associated with a 1.7-fold and 1.35-fold,
      respectively, increased hazard of CHF for each age group, independent of
      anthracycline exposure. Preexisting diabetes was associated with 1.5-fold
      increased hazard of CHF only in those patients aged 66 to 75 years. Patients with
      new-onset CHF had a 18% lower 10-year survival compared with those without CHF.
      CONCLUSIONS: Patients with follicular lymphoma who were exposed to anthracyclines
      between the ages of 66 years and 75 years were found to be at an increased risk
      of new-onset CHF; preexisting hypertension and diabetes appeared to increase this
      risk. The findings of the current study support and inform the risk-based follow
      up of vulnerable populations.

PMID- 30303520
TI  - Treatment of childhood acute lymphoblastic leukemia with delayed first
      intrathecal therapy and omission of prophylactic cranial irradiation: Results of
      the TPOG-ALL-2002 study.
AB  - BACKGROUND: To eliminate cranial irradiation (CrRT)-related sequelae and to
      minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, the
      Taiwan Pediatric Oncology Group (TPOG) introduced a modified central nervous
      system (CNS)-directed regimen characterized by delayed triple intrathecal therapy
      (TIT) and the omission of CrRT for all children with newly diagnosed acute
      lymphoblastic leukemia (ALL). METHODS: This study compared the treatment outcomes
      of patients overall and patients with a non-CNS-1 status (CNS-2, CNS-3, or TLP
      with blasts) in 2 treatment eras, one before and another after the revision of
      the TPOG-ALL-2002 protocol by the introduction of the modification (era 1 [2002
      2008] with CrRT and era 2 [2009-2012] with delayed first TIT and no CrRT).
      RESULTS: There were no statistically significant differences in major outcomes
      between the 903 patients treated in era 1 and the 444 patients treated in era 2:
      the 5-year event-free survival (EFS) rates were 75.7% +/- 1.4% and 72.1% +/-
      2.4%, respectively (P = .260), and the cumulative risks of isolated CNS relapse
      were 4.0% +/- 0.7% and 4.1% +/- 1.0%, respectively (P = .960). There were also no
      differences between non-CNS-1 patients treated in era 1 (n = 76) and era 2 (n
      =28): the 5-year EFS rates were 52.3% +/- 5.8% and 62.9% +/- 9.4%, respectively
      (P = .199), and the cumulative risks of isolated CNS relapse were 6.3% +/- 3.1%
      and 3.6% +/- 3.5%, respectively (P = .639). Notably, TLP with blasts was
      completely eliminated after the first TIT was delayed in era 2. CONCLUSIONS: The
      delay of the first TIT until the clearance of circulating blasts and the total
      omission of CrRT did not compromise survival or CNS control in patients with
      childhood ALL, including those with a non-CNS-1 status.

PMID- 30303523
TI  - A Rapid Method to Estimate Hepatocyte Loss Due to Drug-Induced Liver Injury.
AB  - It is not currently possible to rapidly estimate the extent of hepatocyte loss
      during drug-induced liver injury (DILI). We used a proprietary mechanistic model
      (DILIsym) to estimate percentage hepatocyte loss due to DILI that resulted from
      four different patterns of serum alanine aminotransferase (ALT) over time: rapid
      onset and rapid decrease in ALT levels, moderate onset and moderate decrease in
      ALT levels, moderate onset and extended duration (over 1 month) of ALT
      elevations, and an ALT profile with multiple peaks. Using these data, we derived
      a novel parameter, PALT  = ALT_AUC*Peak ALT0.18 /105 ((IU/L)2 *h), where AUC is
      area under the curve, that correlated well with hepatocyte loss estimates derived
      by DILIsym in patients with DILI due to six different hepatotoxic drugs. Although
      further validation will be required, the fact that PALT can be derived rapidly
      using publicly available pharmacokinetic software may make it a useful parameter
      to improve the safety of drugs.

PMID- 30303524
TI  - Effects of temporal variation in community-level fruit abundance on seed
      dispersal by birds across woody species.
AB  - PREMISE OF THE STUDY: In animal-dispersed plants, seed dispersal patterns of the
      same species in the same habitat can greatly differ among individuals and
      temporally. Many studies have revealed the pervasive effects of spatial variation
      in fruit abundance on seed dispersal of individual plants. By contrast, very few
      studies have investigated the temporal variation in seed dispersal. METHODS: We
      investigated the effects of conspecific and community-level fruit abundance on
      fruit removal rate and seed dispersal distance of six bird-dispersed woody
      species in a Japanese temperate forest for 3 yr. The six species share similar
      fruit characteristics but have different fruiting seasons. In addition, we also
      considered the effects of bird seasonality in diet and species composition on
      seed dispersal. KEY RESULTS: Inter-annual and inter-seasonal variation in
      community-level fruit abundance determined both fruit removal and the seed
      dispersal distance across species, but the effect differed with seasonal changes
      in bird behavior. Abundant fruit satiated fruit removal by birds only during
      fruit-feeding periods, not during insect-feeding periods. A scarcity of fruit
      increased the dispersal distance, but only during the migratory period. This
      difference was probably due to the different foraging behaviors of passing
      migrants and territorial birds. CONCLUSIONS: Our results illustrated that
      temporal variation in community-level fruit abundance could be a determining
      factor for seed dispersal in temperate forests. The effects of temporal
      variations in fruit abundance on seed dispersal patterns should be investigated
      in other ecosystems in order to understand their importance and associations with
      frugivore phenology.

PMID- 30303525
TI  - BOS is associated with decreased HDAC2 from steroid resistant lymphocytes in the
      small airways.
AB  - Immunosuppression therapies including corticosteroids fail to prevent
      bronchiolitis obliterans syndrome (BOS), primarily a disease of the small
      airways, following lung transplantation. We reported increases in steroid
      resistant proinflammatory lymphocytes and their loss of histone deacetylase 2
      (HDAC2), an important mediator of steroid action, in the blood of stable lung
      transplant recipients. We noted similar increases in the steroid-resistant
      lymphocytes in both the blood and small airways in BOS compared with the large
      airways. We hypothesized that these small airway cells would also exhibit a loss
      of HDAC2, and that these changes could be reversed by treatment with theophylline
      (HDAC2 activator). Blood, bronchoalveolar lavage and large and small airway
      brushings were collected from lung transplant patients with BOS (n = 12) or
      stable lung function (n = 18) and healthy aged-matched controls (n = 13).
      Intracellular proinflammatory cytokines [interferon (IFN-gamma) and tumour
      necrosis factor (TNF)-alpha and HDAC2 were measured in CD8+ T, natural killer
      (NK) T-like and NK cells from cultured small airway brushings +/- 5 mg/l
      theophylline +/- 1 uM prednisolone using flow cytometry. Increased small airway
      CD8 T, NK T-like and NK cells were identified in BOS versus stable transplant and
      controls. In BOS, these cells exhibited increased IFN-gamma/TNF-alpha and a loss
      of HDAC2. HDAC2 expression by small airway CD8+ T cells correlated with forced
      expiratory volume in 1 s (FEV1 ) (R = 0.880, P = 0.031). Theophylline and
      prednisolone synergistically up-regulated HDAC2 in CD8+ T cells. BOS is
      associated with loss of HDAC2 from steroid-resistant proinflammatory CD8+ T, NK T
      like and NK cells in the small airways. Therapeutically increasing HDAC2 in these
      lymphocytes may reduce steroid resistance and improve graft survival.

PMID- 30303526
TI  - Response to therapeutic monoclonal antibodies for multiple myeloma in African
      Americans versus whites.
AB  - BACKGROUND: Myeloma occurs disproportionately in African Americans, with
      disparities in outcomes potentially caused by access to care, cytogenetics, and
      immunity. A gap in knowledge of immune function dissimilarities between African
      Americans and whites exists. Data for other diseases suggest innate differences
      in immunity and inflammatory markers, with potential implications for therapeutic
      monoclonal antibodies reliant on secondary immune activation for activity.
      METHODS: Patients receiving daratumumab or elotuzumab, lenalidomide, and
      dexamethasone were retrospectively studied with a primary endpoint of response at
      2 (daratumumab) or 4 months (elotuzumab). Secondary endpoints included stable
      disease or better at the same points, treatment duration, time to best response,
      and adverse events. RESULTS: Eighty patients were included; baseline
      characteristics were balanced with the exception of the stage at diagnosis, which
      was more advanced in African Americans. No statistically significant difference
      in response was seen: 37.9% in whites versus 11.8% in African Americans with
      daratumumab (P = .090) and 60% in whites versus 44% in African Americans with
      elotuzumab (P = .462). There were no differences in the duration of treatment,
      the time to best response, or adverse events. Common potential immune-related
      adverse events in both arms were fatigue (39%), back pain (30%), and infusion
      reactions (40%). Anemia was significantly associated with a response to
      daratumumab (P = .02); no patients without anemia responded at 2 months, whereas
      34.4% of patients with anemia did. CONCLUSIONS: No significant difference in
      response, duration of treatment, or time to response was seen by race, although a
      trend toward greater early response rates in whites was observed. In these
      cohorts, as in other analyses, African American patients tended to present with
      later stage disease.

PMID- 30303527
TI  - The crab spider-pitcher plant relationship is a nutritional mutualism that is
      dependent on prey-resource quality.
AB  - Nutritional mutualisms are one of the three major categories of mutualisms and
      involve the provision of limiting nutrients (resources) to one species by
      another. It was recently shown in laboratory experiments that two species of
      pitcher-dwelling crab spiders (Thomisidae), Thomisus nepenthiphilus and
      Misumenops nepenthicola, increased capture rates of flesh flies (Sarcophagidae)
      for their host, Nepenthes gracilis. The spiders ambushed pitcher-visiting flesh
      flies and dropped their carcasses into pitchers after consuming them. The
      consumption of shared prey-resources by crab spiders and pitcher plants presents
      the possibility of parasitism between them. However, ecologically generalizable
      mechanisms that predict the context-dependent outcomes of such mutualisms are not
      known. The effectiveness framework (mutualism effectiveness = quality * quantity)
      is useful for examining the total effect of mutualisms, but its quality component
      can be difficult to define. We identify the crab spider-pitcher plant interaction
      as a type of resource conversion mutualism and propose that the quality component
      in such interactions is the amount of the underlying resource contained in each
      unit of resource processed. We then used the crab spider-pitcher plant
      interaction to test the hypothesis that resource conversion mutualisms are more
      beneficial to the nutrient recipient when operating through high-quality
      resources (i.e., large prey, in this interaction). We sampled the prey and
      inquilines of 107 N. gracilis upper pitches in situ and analysed the differences
      between pitchers that were inhabited or uninhabited by crab spiders, and the
      differences between nutritional contents of prey that were consumed by crab
      spiders or not. Pitchers inhabited by T. nepenthiphilus contained higher numbers
      of several prey taxa, many of which were flying insects. Consumption by T.
      nepenthiphilus reduced the nutrient contents in all prey examined. Overall, T.
      nepenthiphilus-assisted prey capture is likely to result in a net nutrient gain
      for N. gracilis that is proportional to the size of prey consumed by T.
      nepenthiphilus. Our results suggest that resource conversion mutualisms are more
      likely to operate through high-quality resources, since the nutrient-processing
      species necessarily reduces the quality of the resource it processes while
      increasing its availability to the nutrient recipient species.

PMID- 30303528
TI  - Innovation in Pharmacovigilance: Use of Artificial Intelligence in Adverse Event
      Case Processing.
AB  - Automation of pharmaceutical safety case processing represents a significant
      opportunity to impact the strongest cost driver for a company's overall
      pharmacovigilance budget. A pilot was undertaken to test the feasibility of
      employing artificial intelligence and robotic process automation to automate
      processing of adverse event reports. The pilot paradigm was used to
      simultaneously test proposed solutions of 3 commercial vendors. The result
      confirmed feasibility of using artificial intelligence-based technology to
      support extraction from adverse event source documents and evaluation of case
      validity. In addition, the pilot demonstrated viability of the use of safety
      database data fields as a surrogate for otherwise time-consuming and costly
      direct annotation of source documents. Finally, the evaluation and scoring method
      employed in the pilot was able to differentiate vendor capabilities, and identify
      the best candidate to move into the discovery phase. This article is protected by
      copyright. All rights reserved.

PMID- 30303529
TI  - The modular organization of the cerebral cortex: Evolutionary significance and
      possible links to neurodevelopmental conditions.
AB  - The recognition of discernible anatomical regularities that appear to self
      organize during development makes apparent the modular organization of the
      cerebral cortex. The metabolic cost engendered in sustaining interneuronal
      communications has emphasized the viability of short connections among
      neighboring neurons. This pattern of connectivity establishes a microcircuit
      which is repeated in parallel throughout the cerebral cortex. This canonical
      circuit is contained within the smallest module of information processing of the
      cerebral cortex; one which Vernon Mountcastle called the minicolumn. Plasticity
      within the brain is accounted, in part, by the presence of weak linkages that
      allow minicolumns to process information from a variety of sources and to quickly
      adapt to environmental exigencies without a need for genetic change. Recent
      research suggests that interlaminar correlated firing between minicolumns during
      the decision phase of target selection provides for the emergence of some
      executive functions. Bottlenecks of information processing within this modular
      minicolumnar organization may account for a variety of mental disorders observed
      in neurodevelopmental conditions.

PMID- 30303530
TI  - Intraspecific variation in lizard heat tolerance alters estimates of climate
      impact.
AB  - Research addressing the effects of global warming on the distribution and
      persistence of species generally assumes that population variation in thermal
      tolerance is spatially constant or overridden by interspecific variation.
      Typically, this rationale is implicit in sourcing one critical thermal maximum
      (CTmax ) population estimate per species to model spatiotemporal cross-taxa
      variation in heat tolerance. Theory suggests that such an approach could result
      in biased or imprecise estimates and forecasts of impact from climate warming,
      but limited empirical evidence in support of those expectations exists. We
      experimentally quantify the magnitude of intraspecific variation in CTmax among
      lizard populations, and the extent to which incorporating such variability can
      alter estimates of climate impact through a biophysical model. To do so, we
      measured CTmax from 59 populations of 15 Iberian lizard species (304
      individuals). The overall median CTmax across all individuals from all species
      was 42.8 degrees C and ranged from 40.5 to 48.3 degrees C, with species medians
      decreasing through xeric, climate-generalist and mesic taxa. We found strong
      statistical support for intraspecific differentiation in CTmax by up to a median
      of 3 degrees C among populations. We show that annual restricted activity
      (operative temperature > CTmax ) over the Iberian distribution of our study
      species differs by a median of >80 hr per 25-km2 grid cell based on different
      population-level CTmax estimates. This discrepancy leads to predictions of
      spatial variation in annual restricted activity to change by more than 20 days
      for six of the study species. Considering that during restriction periods,
      reptiles should be unable to feed and reproduce, current projections of climate
      change impacts on the fitness of ectotherm fauna could be under- or over
      estimated depending on which population is chosen to represent the physiological
      spectra of the species in question. Mapping heat tolerance over the full
      geographical ranges of single species is thus critical to address cross-taxa
      patterns and drivers of heat tolerance in a biologically comprehensive way.

PMID- 30303531
TI  - Asymmetric competitive effects during species range expansion: An experimental
      assessment of interaction strength between "equivalent" grazer species in their
      range overlap.
AB  - Biotic interactions are central to the development of theory and concepts in
      community ecology; experimental evidence has shown their strong effects on
      patterns of population and community organization and dynamics over local spatial
      scales. The role of competition in determining range limits and preventing
      invasions at biogeographic scales is more controversial, partly because of the
      complexity of processes involved in species colonization of novel habitats and
      the difficulties in performing appropriate manipulations and controls. We
      examined experimentally whether competition is likely to affect poleward range
      expansion hindering or facilitating the establishment of the limpet Scurria
      viridula along the south-eastern Pacific rocky shore (30 degrees S, Chile) in the
      region occupied by the congeneric S. zebrina. We also assessed whether
      competition with the "invader" or range-expanding species could reduce individual
      performance of the "native" S. zebrina and depress local populations Geographic
      field surveys were conducted to characterize the abundance and identity of
      limpets along the south-eastern Pacific coast from 18 degrees S to 41 degrees S,
      and the micro-scale (few cm) spatial distribution across the range overlap of the
      two species. Field-based competition experiments were conducted at the southern
      leading edge of the range of S. viridula (33 degrees S) and at the northern limit
      of S. zebrina (30 degrees S). Field surveys showed poleward range expansion of S.
      viridula of ca. 210 km since year 2000, with an expansion rate of 13.1 km/year.
      No range shift was detected for S. zebrina. The resident S. zebrina had
      significant negative effects on the growth rate of the invading juvenile S.
      viridula, while no effect of the latter was found on S. zebrina. Spatial
      segregation between species was found at the scale of cms. Our results provide
      novel evidence of an asymmetric competitive effect of a resident species on an
      invader, which may hamper further range expansion. No negative effect of the
      invader on the resident species was detected. This study highlights the
      complexities of evaluating the role of species interactions in setting range
      limits of species, but showed how interspecific competition might slow the
      advance of an invader by reducing individual performance and overall population
      size at the advancing front.

PMID- 30303532
TI  - Prey-specific impact of cold pre-exposure on kill rate and reproduction.
AB  - Temperature influences biological processes of ectotherms including ecological
      interactions, but interaction strengths may depend on species-specific traits.
      Furthermore, ectotherms acclimate to prevailing thermal conditions by adjusting
      physiological parameters, which often implies costs to other fitness-related
      parameters. Both predators and prey may therefore pay thermal acclimation costs
      following exposure to suboptimal temperatures. However, these costs may be
      asymmetrical between predator and prey, and between the predator and different
      species of concurrent prey. We investigated whether thermal pre-exposure affected
      subsequent kill rate and predator fitness when foraging on prey that differ in
      ease of capture, and whether changes were primarily caused by predator or by prey
      pre-exposure effects. Specifically, we were interested in whether there were
      interactions between predator pre-exposed temperature and specific prey. Using
      the mesostigmatid mite Gaeolaelaps aculeifer as a generalist predator and the
      collembolans Folsomia candida and Protaphorura fimata as prey, we measured the
      impact of present temperature, predator pre-exposure temperature, prey pre
      exposure temperature (all 10 or 20 degrees C), prey species, and all interactions
      on prey numbers killed, predator eggs produced, and exploitation of killed prey
      in a full factorial design. Mites killed P. fimata in equal numbers independent
      of the presence of F. candida, but killed F. candida when P. fimata was absent.
      Mite kill rate and reproduction were significantly affected by mite pre-exposure
      temperature and test temperature, but not by prey pre-exposure temperature.
      Significantly more of the slower prey was killed than of the quicker prey.
      Importantly, we found significant synergistic negative interaction effects
      between predator cold pre-exposure and hunting prey of higher agility on predator
      kill rate and reproduction. Our findings show that the negative effects of cold
      and cold pre-exposure on kill rate and reproduction may be more severe when
      predators forage on quick prey. The study implies that predator cold exposure has
      consequences for specific prey survival following cold due to altered predation
      pressures, which in nature should influence the specific prey population dynamics
      and apparent competition outcomes. The findings exemplify how not only current
      but also preceding conditions affect ecological interactions, and that effect
      strength depends on the species involved.

PMID- 30303533
TI  - When can competition and dispersal lead to checkerboard distributions?
AB  - Checkerboard distributions-mutually exclusive species co-occurrences-are a common
      observation in community ecology and biogeography. While the underlying causes of
      checkerboard distributions have remained elusive, a long-standing argument is
      that they are representative of strong competitive interactions and/or dispersal
      limitation. We explore this using a stochastic two-patch metacommunity model
      combined with an experimental two-patch system of competing Tribolium species,
      quantifying checkerboard distributions using the abundance-based index Ast . We
      find that maintenance of checkerboard distributions is possible in a limited
      parameter space consisting of low dispersal rates, low population growth rates
      and high interspecific competition. Checkerboards were not maintained in
      experimental metacommunities. Our model, parameterized using independent data,
      echoed this finding, providing a clear link between model and experiment, and
      suggested that only small regions of parameter space would allow for checkerboard
      distributions between patches with equally hospitable environments. These
      findings may provide insight into when interspecific competition and dispersal
      limitation would promote checkerboard distributions.

PMID- 30303534
TI  - Toward the control of cancer.

PMID- 30303535
TI  - Decreased RORC expression and downstream signaling in HTLV-1-associated Adult T
      cell Lymphoma/Leukemia uncovers an antiproliferative IL17 link: a potential
      target for immunotherapy?
AB  - Retinoic acid-related drugs have shown promising pre-clinical activity in Adult T
      cell Leukemia/Lymphoma, but RORC signaling has not been explored. Therefore, we
      investigated transcriptome-wide interactions of the RORC pathway in HTLV-1 and
      ATL, using our own and publicly available gene expression data for ATL and other
      leukemias. Gene expression data from ATL patients were analyzed using WGCNA to
      determine gene modules and their correlation to clinical and molecular data. Both
      PBMCs and CD4+ T-cells showed decreased RORC expression in four different ATL
      cohorts. A small subset of RORChi ATL patients was identified with significantly
      lower pathognomonic CADM1 and HBZ levels but similar levels of other ATL markers
      (CD4/CD25/CCR4), hinting at a less aggressive ATL subtype. An age-dependent
      decrease in RORC expression was found in HTLV-1-infected individuals, but not in
      healthy controls, suggesting an early molecular event predisposing to
      leukemogenesis. Genes upstream of RORC signaling were members of a proliferative
      gene module (containing proliferation markers PCNA/Ki67), whereas downstream
      members clustered in an anti-proliferative gene module. IL17C transcripts showed
      the strongest negative correlation to PCNA in both ATL cohorts, which was
      replicated in two large cohorts of T- and B-cell acute lymphoid leukemia (ALL).
      Finally, IL17C expression in purified CD4+CCR4+CD26-CD7- 'ATL-like' cells from
      HTLV-1-infected individuals and ATL patients was negatively correlated with
      clonality, underscoring a possible antileukemic/antiproliferative role. In
      conclusion, decreased RORC expression and downstream signaling might represent an
      early event in ATL pathogenesis. An antiproliferative IL17C/PCNA link is shared
      between ATL, T-ALL and B-ALL, suggesting (immuno)therapeutic benefit of boosting
      RORC/IL17 signaling. This article is protected by copyright. All rights reserved.

PMID- 30303538
TI  - Objective effectiveness of and indications for laser-assisted turbinectomy in
      brachycephalic obstructive airway syndrome.
AB  - OBJECTIVE: To evaluate the effectiveness of laser-assisted turbinectomy (LATE) in
      treating brachycephalic obstructive airway syndrome (BOAS) and to investigate the
      potential indications. STUDY DESIGN: Prospective clinical study. SAMPLE
      POPULATION: Client-owned pugs, French bulldogs, and English bulldogs (n = 57).
      METHODS: A BOAS index was obtained from whole-body barometric plethysmography
      before BOAS conventional multilevel surgery (CMS) and 2-6 months post-CMS. Dogs
      with BOAS index >50% and BOAS functional grades II-III after CMS were considered
      candidates for LATE. A BOAS index was repeated 2-6 months after LATE. Intranasal
      lesions and a measurement of soft tissue proportion at the rostral entrance of
      choanae (STC) were recorded on the basis of computed tomography images. Logistic
      regressions were used to assess the intranasal predictors for being LATE
      candidates. RESULTS: Twenty-nine of 57 dogs were candidates for LATE, all of
      which were pugs or French bulldogs. The median BOAS index of dogs that were
      operated on (20/29 candidates) decreased from 67% post-CMS to 42% after LATE (P <
      .001). Soft tissue proportion at the rostral entrance of choanae was the only
      predictor for candidacy for LATE. Pugs (P = .021; cutoff = 64%) and French
      bulldogs (P = .008; cutoff = 55%) with higher STC were more likely to be
      candidates for LATE. After LATE, 12 of 20 dogs had temporary episodes of reverse
      sneezing, and nasal noise was noted in 8 of 20 dogs when sniffing and excited.
      CONCLUSION: Laser-assisted turbinectomy was an effective treatment for dogs with
      intranasal abnormalities and a poor response to CMS. Soft tissue proportion at
      the rostral entrance of choanae was a predictor of candidacy for LATE in pugs and
      French bulldogs. CLINICAL SIGNIFICANCE: Computed tomography-based measurement of
      STC can be used to predict whether LATE is required in addition to CMS in pugs
      and French bulldogs with BOAS.

PMID- 30303539
TI  - Can subunit-specific phenotypes guide surveillance imaging decisions in
      asymptomatic SDH mutation carriers?
AB  - OBJECTIVE: With the discovery that familial phaeochromocytoma and paraganglioma
      syndrome can be caused by mutations in each subunit of the succinate
      dehydrogenase enzyme (SDH), has come the recognition that mutations in the
      individual subunits have their own distinct natural histories. Increased genetic
      screening is leading to the identification of increasing numbers of, mostly
      asymptomatic, gene mutation carriers and the implementation of screening
      strategies for these individuals. Yet there is, to date, no international
      consensus regarding screening strategies for asymptomatic carriers. DESIGN: A
      comprehensive PubMed search from 1/1/2000 to 28/2/2018 was undertaken using
      multiple search terms and subsequently a manual review of references in
      identified papers to identify all clinically relevant cases and cohorts. In this
      review, the accumulated, published experience of phenotype and malignancy risks
      of individual SDH subunits is analysed. Where possible screening results for
      asymptomatic SDH mutation carriers have been analysed separately to define the
      penetrance in asymptomatic carriers (asymptomatic penetrance). RESULTS: The
      combined data confirms that "asymptomatic penetrance" is highest for SDHD and
      when there is penetrance, the most likely site to develop a PGL is head and neck
      (SDHD) and extra-adrenal abdominal (SDHB). However, the risk in SDHB carriers of
      developing HNPGL is also high (35.5%) and a PCC is low (15.1%), and in SDHD
      carriers there is a high risk of developing a PCC (35.8%) or abdominal PGL (9.4%)
      and a small, but significant risk at other sympathetic sites. The data suggest
      that the risk of malignant transformation is the same for both PCC and extra
      adrenal abdominal PGLs (30%-35%) in SDHB carriers. In SDHD carriers, the risk of
      malignant transformation was highest in HNPGLs (7.5%) and similar for sympathetic
      sites (3.8%-5.2%). CONCLUSIONS: Using this data, we suggest surveillance
      screening of asymptomatic carriers can be tailored to the underlying SDH subunit
      and review possible surveillance programmes.

PMID- 30303540
TI  - Tibial plateau morphology in dogs with cranial cruciate ligament insufficiency.
AB  - OBJECTIVE: To identify possible biomechanical causes for the predominantly
      unilateral presentation of cranial cruciate ligament (CCL) insufficiency by
      comparing the computed tomographic (CT) features of the tibial plateau of CCL
      affected and contralateral sound stifles in dogs with unilateral CCL
      insufficiency. STUDY DESIGN: Cross-sectional study. ANIMALS: Eighteen dogs, 36
      stifles. METHODS: Eighteen dogs with naturally occurring unilateral CCL
      insufficiency were included. Stifle CT and radiographs were performed at the time
      of diagnosis. Follow-up was performed at a minimum of 1 year from the original
      diagnosis to ensure that there was no evidence of contralateral CCL
      insufficiency. The medial tibial plateau angle (m-TPA), lateral TPA (and l-TPA),
      medial tibial plateau midsagittal radius of curvature (m-TPr), and lateral TPr (l
      TPr) were measured from the CT images. Variables were compared with paired t
      tests. A Bonferroni correction was performed, and P < .006 was considered
      significant. RESULTS: Mean m-TPr was steeper (P = .002) and m-TPr:l-TPr ratio was
      greater (P < .001) in affected stifles compared with contralateral sound stifles.
      No other variables differed between groups. Mean l-TPA was steeper than mean m
      TPA (P < .001). CONCLUSION: Tibial plateau convexity differed between the CCL
      affected and contralateral sound stifle in dogs with unilateral CCL
      insufficiency. CLINICAL SIGNIFICANCE: Medial tibial plateau convexity may play a
      role in the development of CCL insufficiency.

PMID- 30303536
TI  - From colorectal cancer pattern to the characterization of individuals at risk:
      Picture for genetic research in Latin America.
AB  - Colorectal cancer (CRC) is one of the most common cancers in Latin America and
      the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina.
      We provide a global snapshot of the CRC patterns, how screening is performed, and
      compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region.
      From the literature, we find that only nine (20%) of the Latin America and the
      Caribbean countries have developed guidelines for early detection of CRC, and
      also with a low adherence. We describe a genetic profile of LS, including a total
      of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and
      Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most
      commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM
      variants were most frequently identified in Colombia (80%) and Argentina (47%).
      Path_MSH6 and path_PMS2 variants were less common, but they showed important
      presence in Brazil (15%) and Chile (10%), respectively. Important differences
      exist at identifying LS families in Latin American countries, where the spectrum
      of path_MLH1 and path_MSH2 variants are those most frequently identified. Our
      findings have an impact on the evaluation of the patients and their relatives at
      risk for LS, derived from the gene affected. Although the awareness of hereditary
      cancer and genetic testing has improved in the last decade, it is remains
      deficient, with 39%-80% of the families not being identified for LS among those
      who actually met both the clinical criteria for LS and showed MMR deficiency.

PMID- 30303541
TI  - Relationship between renal CD68+ infiltrates and the oxford classification of iga
      nephropathy.
AB  - AIMS: The Oxford Classification E score (endocapillary hypercellularity) predicts
      renal functional decline in IgA nephropathy (IgAN) patients free from
      steroid/immunosuppressive (IS) therapy, but is poorly reproducible. We
      hypothesise that endocapillary hypercellularity reflects glomerular inflammation
      and that the presence of CD68-positive cells is a more robust marker of E score.
      METHODS AND RESULTS: CD68 positive cells were quantified in glomeruli and
      tubulointerstitium in biopsies from 118 IgAN patients, and cell counts were
      correlated with the criteria of the Oxford Classification, assigned on PAS
      stained serial sections. There was a strong correlation between median glomerular
      CD68 count and the percentage of glomeruli showing endocapillary hypercellularity
      (r=0.67; p<0.001; r2 =0.45) whilst there was no correlation between CD68-positive
      cells and mesangial hypercellularity, % segmental sclerosis, % of crescents and %
      tubular atrophy/interstitial fibrosis (TA/IF). ROC curve analysis demonstrated
      that a maximum glomerular CD68 count of 6 is the best cut-off for distinguishing
      E0 from E1 (sensitivity 94.1%, specificity 71%, area under the curve = 89%).
      Identification of biopsies with a maximum glomerular CD68-count >6 was
      reproducible (kappa score 0.8), and there was a strong correlation between
      glomerular CD68 counts obtained by conventional light microscopy and by image
      analysis (r=0.80, r2 =0.64, p=<0.0001). Digital image analysis revealed that
      tubulointerstitial CD68-positive cells correlated moderately with % TA/IF
      (r=0.59, r2 =0.35, p=<0.001) and GFR at the time of biopsy (r=0.54, r2 =0.29,
      p=<0.0001), but not with mesangial and endocapillary hypercellularity.
      CONCLUSIONS: Whilst glomerular CD68-positive cells emerge as markers of
      endocapillary hypercellularity, their tubulointerstitial counterparts are
      associated with chronic damage. This article is protected by copyright. All
      rights reserved.

PMID- 30303542
TI  - Intravenous Lidocaine for Acute Pain: A Systematic Review.
AB  - This systematic review evaluates the safety and efficacy of intravenous (IV)
      lidocaine for the treatment of acute pain in adult patients. The PubMed database
      was searched for randomized controlled trials, retrospective cohort studies, case
      series, and case reports evaluating the use of IV lidocaine for the treatment of
      acute pain in adult patients, published between January 1970 and January 2018.
      The primary outcome was pain reduction via the Visual Analog Scale, Verbal Rating
      Scale, or Numeric Rating Scale among patients treated with IV lidocaine and
      placebo or active controls. Safety outcomes included both nonserious and serious
      adverse events. A total of 347 titles and abstracts were screened, and after full
      text review, 13 studies met the inclusion criteria involving 512 patients. The
      four active controls studied were IV morphine, IV ketorolac, IV dihydroergotamine
      (DHE), and IV chlorpromazine (CPZ). The dosing of IV lidocaine varied among
      studies between a weight-based dose of a 1- to 2-mg/kg bolus, a fixed-bolus dose
      of 50-100 mg, and a 1-mg/kg/hour continuous infusion. Monitoring of serum
      lidocaine concentrations was not done routinely. Intravenous lidocaine had
      superior efficacy to morphine for renal colic and critical limb ischemia,
      superior efficacy to DHE for acute migraine, and equivalent efficacy to ketorolac
      for acute radicular lower back pain. However, lidocaine was less effective than
      CPZ for the treatment of acute migraine. The most common adverse event reported
      among all studies were neurologic effects such as altered mental status and
      slurred speech. Due to the inconsistency in dosing, length of administration, and
      lack of serum monitoring, the absolute safety of IV lidocaine for acute pain is
      unknown. Larger, prospective studies are needed before the routine use of IV
      lidocaine can be recommended for all types of acute pain.

PMID- 30303537
TI  - Familial breast cancer and DNA repair genes: Insights into known and novel
      susceptibility genes from the GENESIS study, and implications for multigene panel
      testing.
AB  - Pathogenic variants in BRCA1 and BRCA2 only explain the underlying genetic cause
      of about 10% of hereditary breast and ovarian cancer families. Because of cost
      effectiveness, multigene panel testing is often performed even if the clinical
      utility of testing most of the genes remains questionable. The purpose of our
      study was to assess the contribution of rare, deleterious-predicted variants in
      DNA repair genes in familial breast cancer (BC) in a well-characterized and
      homogeneous population. We analyzed 113 DNA repair genes selected from either an
      exome sequencing or a candidate gene approach in the GENESIS study, which
      includes familial BC cases with no BRCA1 or BRCA2 mutation and having a sister
      with BC (N = 1,207), and general population controls (N = 1,199). Sequencing data
      were filtered for rare loss-of-function variants (LoF) and likely deleterious
      missense variants (MV). We confirmed associations between LoF and MV in PALB2,
      ATM and CHEK2 and BC occurrence. We also identified for the first time
      associations between FANCI, MAST1, POLH and RTEL1 and BC susceptibility. Unlike
      other associated genes, carriers of an ATM LoF had a significantly higher risk of
      developing BC than carriers of an ATM MV (ORLoF = 17.4 vs. ORMV = 1.6; p Het =
      0.002). Hence, our approach allowed us to specify BC relative risks associated
      with deleterious-predicted variants in PALB2, ATM and CHEK2 and to add MAST1,
      POLH, RTEL1 and FANCI to the list of DNA repair genes possibly involved in BC
      susceptibility. We also highlight that different types of variants within the
      same gene can lead to different risk estimates.

PMID- 30303543
TI  - Biomechanical properties of celiotomy wounds closed with tape and cyanoacrylate
      versus intradermal sutures.
AB  - OBJECTIVE: To compare cutaneous wound closure with mesh and 2-octyl cyanoacrylate
      (MOC) vs an intradermal suture pattern (ISP) in terms of time of application and
      biomechanical properties. SAMPLE POPULATION: Experimental study with 12 female
      beagle dogs. METHODS: A skin incision was created from the xiphoid to the pubis
      as part of an ovariohysterectomy; the linea alba and subcutaneous tissue were
      closed routinely. Half of the skin incision was closed with MOC, and the other
      half was closed with an ISP. Tissue samples were collected from both sections at
      days 14 and 28 and tested for ultimate strength and stiffness. RESULTS: Closure
      with MOC (72.8 +/- 14.0 s) was faster than with an ISP (398.4 +/- 36.4 s; P =
      .001). The ultimate load and stiffness increased with time for MOC (P = .005 and
      P = .005, respectively) and ISP (P < .001 and P < .001, respectively). On day 14,
      ultimate load and stiffness were greater in wounds closed with MOC compared with
      ISP (P = .014 and P = .02, respectively). No difference between groups was
      detected at day 28. CONCLUSION: Cutaneous wound closure with MOC was faster and
      resulted in superior strength at 14 days compared with closure with an ISP in
      this healthy population. CLINICAL SIGNIFICANCE: Mesh and 2-octyl cyanoacrylate
      offers an attractive alternative to ISP for skin closure after celiotomy in dogs,
      especially if surgical/anesthesia time is a concern.

PMID- 30303544
TI  - Some recommendations for experimental work in magnetobiology, revisited.

PMID- 30303545
TI  - Mucor sp.-An endophyte of Brassicaceae capable of surviving in toxic metal-rich
      sites.
AB  - The aim of this study was to assess the biodiversity of endophytic fungi from
      Arabidopsis arenosa growing on a post mining waste dump and to evaluate their
      role in plant adaptation to metal toxicity. Severeal of the fungi were beneficial
      for the plant. Among them, a fungus belonging to the Mucor genus, was found to
      interact with a broad range of plants, including Brassicaceae metallophytes.
      Mucor sp. was shown to be highly tolerant to elevated levels of Zn, Cd, and Pb
      and to accelerate plant-host growth under either toxic-metal stress or control
      conditions. When inoculated with Mucor sp., A. arenosa under toxic-metal stress
      acquired more N and showed significantly down-regulated catalase activity, which
      suggests suppression of toxic-metal-induced oxidative stress. We used the model
      plant-A. thaliana to evaluate the dynamics of plant-tissue colonization by the
      fungus as monitored with qPCR and to analyze the host's transcriptome response
      during early stages of the interaction. The results revealed the induction of a
      plant-defense and stress-related response on the 5th day of co-culture, which was
      in accord with the decrease of fungal abundance in shoots on the 6th day of
      interaction. Presented results demonstrate the importance of endophytic fungi in
      plant toxic-metal tolerance.

PMID- 30303546
TI  - Influence of the emollient on emulsions containing lamellar liquid crystals: from
      molecular organization towards applicative properties.
AB  - OBJECTIVE: The sensory perception of cosmetic emulsions is complex as it is
      governed by an important number of parameters like the choice of raw materials,
      their interactions, the structural organisation of the system, etc. The aim of
      the present work was to go further in the interpretation of the emollient
      surfactant interactions, towards the emulsions applicative properties. For this
      purpose, two systems containing liquid crystals of the lamellar type were
      formulated, differing only in the selected emollient. METHODS: First, the liquid
      crystals types were checked using different tools like the optical microscopy
      under the bright and polarized light, the wide-angle X rays diffraction and,
      finally, thermogravimetric analysis. Next, two sensory attributes, namely
      compression force and difficulty of spreading, were evaluated by a sensory panel.
      In addition to that, complementary instrumental characterizations (flow tests,
      textural analysis and contact angle measurements) were performed in order to
      understand how the panel could discriminate the products. RESULTS: The results
      showed that isohexadecane emollient induces the alpha-gel structures, while
      caprylic capric triglycerides favour the formation of the lamellar liquid
      crystals near to alpha-gel. For the compression force, the results point out that
      there is no direct interaction between the oil phase and the skin. For this
      attribute, depending on its chemical structure, emollient impacts the human
      perception only by changing the lamellar phase type. Concerning the difficulty of
      spreading, both the emulsion structure and the emollient properties should be
      considered. Immediate perception is impacted by the emulsions destruction, making
      the droplet roll one on each other. Then, once the droplets monolayer is
      disrupted, the emollient comes into direct contact with the skin. In this case,
      the perception is governed by the direct affinity of the emollient with the skin,
      nonpolar emollients being easier to spread if compared to polar ones. CONCLUSION:
      The sensory perception is guided not only by the choice of the raw materials but
      also by their interactions. It was shown that the chemical structure of the
      emollients affected the molecular organization of liquid crystals present in the
      emulsion and, consequently, directly or indirectly its sensory perception.

PMID- 30303547
TI  - Community structure and fibrolytic activities of anaerobic rumen fungi in
      dromedary camels.
AB  - Anaerobic fungi colonize the rumen and degrade cellulose and hemicellulose, which
      enable them to be key players in the lignocellulose fermentation. Consequently,
      an expansion of knowledge about rumen fungi could increase animal productivity,
      utilization of lignified forages like alfalfa hay, and enhance fibrolytic enzymes
      production. Here, we used an Internal Transcribed Spacer 1 (ITS1) clone library
      to investigate the anaerobic rumen fungi in camel and to investigate their
      ability to produce cellulase and xylanase in vitro. Rumen fluid was collected
      from camels fed Egyptian clover (n = 14), and wheat straw (n = 7) and fecal
      samples were collected from camels fed wheat straw and concentrates (n = 5), or
      natural grazing plants (n = 10). Neocallimastix and Cyllamyces were the most
      abundant anaerobic fungi in all camel groups. An anaerobic rumen fungi media
      containing alfalfa hay as a carbon source was inoculated by rumen and fecal
      samples to assess the ability of anaerobic rumen fungi in camel gut to produce
      cellulase and xylanase. The anaerobic gut fungi in the camel is diverse and has
      cellulolytic and xylanolytic activities, fungal culture from rumen samples of
      camel fed wheat straw (R2) exhibited highest cellulase production. In addition,
      many of the sequences in the current study have no equivalent cultured
      representative, indicating a novel diversity within the camel gut.

PMID- 30303548
TI  - Lung lobe torsion in dogs: 52 cases (2005-2017).
AB  - OBJECTIVE: To report outcomes and risk factors for mortality in dogs that
      underwent surgical management of lung lobe torsion. STUDY DESIGN: Retrospective
      case series from 5 veterinary teaching hospitals (2005-2017). ANIMALS: Fifty dogs
      with 52 instances of lung lobe torsion. METHODS: Data collected from medical
      records included signalment, clinical findings, results of clinicopathologic
      testing and diagnostic imaging, surgical treatment, lung lobe affected,
      intraoperative and postoperative complications, histopathologic and microbiologic
      findings, and outcome. Follow-up was obtained from medical records and telephone
      contact with primary care veterinarians. RESULTS: Fifty-two instances of lung
      lobe torsion were identified in 50 dogs, with a median follow-up of 453 days
      (range, 0-3075). Forty-six (92%) dogs survived to discharge. Dogs with concurrent
      torsion of the right cranial and middle lung lobes were less likely to survive
      (2/4) than those with torsion of the left cranial lung lobe (22/22). No other
      risk factors for mortality prior to hospital discharge were identified. Overall
      median survival time after hospital discharge was 1369 days. Four dogs had >1
      episode of lung lobe torsion. CONCLUSION: The percentage of dogs surviving to
      discharge after surgical treatment of lung lobe torsion was higher than
      previously reported. The short- and long-term prognosis was excellent with
      surgical treatment of lung lobe torsion. CLINICAL SIGNIFICANCE: Surgery should be
      recommended when lung lobe torsion is suspected because of the high survival to
      discharge rate and excellent long-term prognosis.

PMID- 30303549
TI  - Comparison of bleach, acetic acid, and other topical anti-infective treatments in
      pediatric atopic dermatitis: A retrospective cohort study on antibiotic exposure.
AB  - BACKGROUND/OBJECTIVES: Skin infection is common in atopic dermatitis (AD), often
      necessitating treatment with systemic antibiotics. Topical adjunctive therapies
      such as dilute bleach baths are increasingly recommended, and topical dilute
      acetic acid (AA) has not been widely studied. The objective of this study was to
      evaluate whether various topical anti-infective bathing recommendations were
      associated with decreased systemic antibiotic exposure in pediatric AD, as well
      as evaluate topical anti-infective recommendations over time within our
      institution. METHODS: Clinical data were extracted from charts of pediatric
      patients from 1/1/2000 to 12/31/2005 and 1/1/2009 to 12/31/2014 who visited
      outpatient dermatology clinics at Mayo Clinic, Rochester, a tertiary referral
      center. Recommendations for topical anti-infectives (dilute AA, dilute bleach,
      other, or none) at any time after patient had clinically proven or suspected AD
      superinfection were recorded as exposures to topical anti-infective. Primary
      outcome was the number of systemic antibiotic courses in a 1-year period.
      RESULTS: Of 1111 patients with AD, 753 met inclusion criteria (303 in 2000-2005;
      450 in 2009-2014). Of these, 351 (46.6%) had culture-proven or clinically
      suspected superinfection. Topical anti-infective recommendations increased
      between the time periods (23.3% to 79.2%; P < 0.001) and number of courses of
      systemic antibiotics decreased (1.9 per year vs 1.5 per year, P = 0.010). Number
      of systemic antibiotic courses did not differ between those who received bathing
      recommendations and those who did not, nor between different anti-infective
      groups (P = 0.398). CONCLUSIONS: Practice behaviors have changed, and topical
      anti-infectives are now commonly recommended. Neither dilute AA nor bleach baths
      were associated with fewer subsequent exposures to systemic antibiotics in the
      treatment of pediatric AD.

PMID- 30303550
TI  - Mapping connectomes with diffusion MRI: deterministic or probabilistic
      tractography?
AB  - PURPOSE: Human connectomics necessitates high-throughput, whole-brain
      reconstruction of multiple white matter fiber bundles. Scaling up tractography to
      meet these high-throughput demands yields new fiber tracking challenges, such as
      minimizing spurious connections and controlling for gyral biases. The aim of this
      study is to determine which of the two broadest classes of tractography
      algorithms-deterministic or probabilistic-is most suited to mapping connectomes.
      METHODS: This study develops numerical connectome phantoms that feature realistic
      network topologies and that are matched to the fiber complexity of in vivo
      diffusion MRI (dMRI) data. The phantoms are utilized to evaluate the performance
      of tensor-based and multi-fiber implementations of deterministic and
      probabilistic tractography. RESULTS: For connectome phantoms that are
      representative of the fiber complexity of in vivo dMRI, multi-fiber deterministic
      tractography yields the most accurate connectome reconstructions (F-measure =
      0.35). Probabilistic algorithms are hampered by an abundance of false-positive
      connections, leading to lower specificity (F = 0.19). While omitting connections
      with the fewest number of streamlines (thresholding) improves the performance of
      probabilistic algorithms (F = 0.38), multi-fiber deterministic tractography
      remains optimal when it benefits from thresholding (F = 0.42). CONCLUSIONS: Multi
      fiber deterministic tractography is well suited to connectome mapping, while
      connectome thresholding is essential when using probabilistic algorithms.

PMID- 30303551
TI  - Is this the Last Requiem for Simtuzumab? - "Blessed is who expects nothing, for
      he shall never be disappointed." - Alexander Pope.
AB  - In modern hepatology we sing the song for the advent of effective antifibrotic
      drugs for decades recalling the line of a masterpiece song of the late Leonard
      Cohen "a million candles burning for the help that never came". We realize but
      hardly accept that most likely such drugs will not work without resolving the
      causative problem of a liver disease such as in viral hepatitis. In liver
      diseases with so far unknown etiology as in primary sclerosing cholangitis (PSC),
      the task of successful antifibrotic treatment will even harder be pursued. This
      article is protected by copyright. All rights reserved.

PMID- 30303552
TI  - Effect of surgical site infection on survival after limb amputation in the
      curative-intent treatment of canine appendicular osteosarcoma: a Veterinary
      Society of Surgical Oncology retrospective study.
AB  - OBJECTIVE: To determine the influence of surgical site infection (SSI) on the
      median disease-free interval (DFI) and median survival time (MST) in dogs after
      amputation in the curative-intent treatment of appendicular osteosarcoma (OSA).
      STUDY DESIGN: Multi-institutional retrospective cohort study. ANIMALS: Fifteen
      dogs with OSA and SSI, and 134 dogs with OSA and no SSI. METHODS: Medical records
      were reviewed, and dogs were included if the following criteria were met:
      histologic confirmation of OSA, no evidence of metastasis, >=1 chemotherapy
      treatment, and available follow-up data. We used the definition of SSI from the
      Centers for Disease Control and Prevention. Kaplan-Meier estimates of median DFI
      and MST for the SSI and non-SSI groups were compared by log-rank test. Univariate
      and multivariate Cox proportional hazard regression analysis was evaluated for
      associations with DFI and survival. RESULTS: The median DFI and MST of all OSA
      dogs were 236 days (95% CI, 181-283) and 283 days (95% CI 237-355), respectively.
      The median DFI of dogs with SSI (292 days) did not differ from that of dogs
      without SSI (224 days, P = .156). The MST of dogs with SSI (292 days) did not
      differ from that of dogs without SSI (280 days, P = .417). Failure to complete
      chemotherapy was associated with decreased DFI and survival (P < .001).
      Adjustments for chemotherapy completion found no effect of SSI on survival.
      CONCLUSION: SSI did not influence the survival of dogs with appendicular OSA
      treated with amputation and curative-intent treatment. CLINICAL SIGNIFICANCE: The
      extended survival associated with SSI after limb-spare surgery for OSA does not
      appear to be present after amputation. Interactions between the canine immune
      system and OSA warrant additional study.

PMID- 30303553
TI  - Combined imaging and shimming with the dynamic multi-coil technique.
AB  - PURPOSE: Spatial encoding and shimming in MRI have traditionally been performed
      using dedicated coils that generate orthogonal spherical harmonic fields. The
      recently introduced multi-coil hardware has proven that MRI-relevant magnetic
      fields can also be created by a generic set of localized coils producing non
      orthogonal fields. As a step towards establishing a purely multi-coil-based MRI
      field generation system, the feasibility of performing conventional Cartesian k
      space encoding and echo-planar imaging (EPI), as well as concurrent encoding and
      shimming is demonstrated in this study. METHODS: We report the use of Dynamic
      Multi-Coil Technique (DYNAMITE) for combined Cartesian encoding and shimming, and
      EPI using a 48-channel multi-coil system. Experiments were performed on phantom
      objects and biological specimens in a 9.4 T pre-clinical scanner. Cartesian
      Fourier-encoded MRI and EPI were implemented whereby the magnetic fields required
      for encoding of the three orthogonal spatial dimensions were entirely based on
      linear combinations of multi-coil fields. Furthermore, DYNAMITE imaging was
      augmented by concurrent DYNAMITE shimming with the same hardware. RESULTS:
      DYNAMITE-based MR and echo-planar images were indistinguishable from those
      acquired with the conventional linear imaging gradients provided by the scanner.
      In experiments with concurrent DYNAMITE shimming and imaging, shim challenges
      that would result in extreme spatial distortion and signal loss were corrected
      very effectively with more than 92% signal recovery in case of extreme Z2 shim
      challenge that resulted in complete signal dephasing in most slices. CONCLUSIONS:
      We demonstrate the first successful implementation of combined DYNAMITE imaging
      and shimming and show the feasibility of performing EPI with DYNAMITE hardware.
      Our results substantiate the potential of multi-coil hardware as a full-fledged
      imaging and shimming system, with additional potential benefits of reduced echo
      time and risk of peripheral nerve stimulation while performing EPI.

PMID- 30303554
TI  - Expression and polymorphism of micro-RNA according to body mass index and breast
      cancer presentation in Tunisian patients.
AB  - Micro-RNAs (miRs) constitute a class of small noncoding RNAs implicated in the
      regulation of gene expression by binding to target mRNAs. A miR can target
      several mRNAs, being involved in different biologic processes and pathologies.
      This pleiotropic function might explain the link between diseases co-occurrence.
      Epigenetic origin of the link between obesity and breast cancer (BC) is
      investigated in a cohort of Tunisian patients, focusing on polymorphism at
      germline level (miR-146a) and on expression in mammary tumors (miR-21, miR-146a,
      and miR-34a), according to body mass index (BMI) and clinico-pathologic features.
      The measure of miR expression in 60 mammary tumors was realized using
      quantitative RT-PCR. Study of rs 2910164 in miR-146a was performed by PCR and
      direct sequencing using blood DNA of 83 affected women and 50 unrelated subjects
      from Great Tunis. MiR-21, miR-146a, and miR-34a have been quantified in breast
      tumor according to BMI. MiR-21 is significantly more expressed in tumors of obese
      women comparatively to nonobese patients. On the contrary, miR-34a is decreased
      in tumors of obese women. Moreover, in obese BC patients, a significant increase
      in both miR-21 and miR-146a expression is revealed in cases with lymph node
      metastasis. The polymorphism at rs 2910164 (miR-146a) locus was not shown as a
      risk factor for BC. However the mutant CC genotype was revealed to be associated
      with a risk for bad outcome of the disease. Chronic inflammation in obese women
      would be linked to aggressive breast tumors via induction of oncomiRs
      overexpression and decrease of tumor suppressor miRs.

PMID- 30303555
TI  - Gait biomechanics after combined HTO-ACL reconstruction versus HTO alone: A
      matched cohort study.
AB  - The purpose of the present study was to compare bilateral external knee moments
      during gait in patients with concomitant medial compartment knee OA, varus
      alignment and chronic anterior cruciate ligament (ACL) deficiency who underwent
      either medial opening-wedge high tibial osteotomy alone (HTO) or simultaneous HTO
      and ACL reconstruction (HTO-ACLR). Fifty-two patients (26 matched pairs)
      completed 3D gait analysis preoperatively and at a minimum 5 years
      postoperatively. Patients were matched for preoperative age, sex, body mass index
      and magnitude of correction. Primary outcomes selected a priori were the peak
      knee adduction moment (KAM) and knee flexion (KFM) moment during stance. Moments
      were compared using mixed model repeated measures analysis of variance (ANOVA).
      For the peak KAM, there was a significant time by limb interaction. For both
      groups, there were similar reductions in the peak KAM 5 years postoperatively in
      the surgical limb only [-1.34 %BW * Ht (-1.71, -0.96) and -1.72 %BW * Ht (-1.99, 
      1.44) for HTO and HTO-ACLR, respectively]. For the peak KFM, there was a
      significant time by group by limb interaction. There was a decrease in the peak
      KFM 5 years postoperatively in the HTO group [-0.88 %BW * Ht (-1.45, -0.31)] but
      not in the HTO-ACLR group [0.03 %BW * Ht (-0.43, 0.48)]. These results suggest
      that individuals with medial knee OA, varus alignment and chronic ACL deficiency
      who undergo simultaneous medial opening-wedge HTO and ACL reconstruction may not
      experience the same long-term (5 year) changes in sagittal plane knee
      biomechanics observed in patients undergoing HTO alone. (c) 2018 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

PMID- 30303556
TI  - Solution dynamics of 5-fluorouracil entrapped in poly lactic-co-glycolic acid
      (PLGA) microsphere-A study with 1D selective NMR methods.
AB  - In this report, our main focus is to introduce a set of one-dimensional (1D) NMR
      methods based on chemical shift, relaxation, and magnetization transfer, namely,
      NOE and chemical exchange involving selective pulse excitation to study the
      solution dynamics of drug in free and encapsulated state within polymeric
      microsphere. In this regard 5-fluorouracil (5-FU) loaded poly lactic-co-glycolic
      acid (PLGA) microspheres are prepared as model system via standard water-in-oil
      in-water emulsification method. One-dimensional 1 H and 19 F nuclear magnetic
      resonance (NMR) spectra of 5-FU in presence of PLGA microspheres presented a
      significant change in linewidth and relaxation rates compared with free 5-FU
      confirming encapsulation. Furthermore, loss of coupling pattern in 1 H and 19 F
      NMR of PLGA encapsulated 5-FU as compared with free 5-FU suggests an enhanced -NH
      and -H2 O protons exchange dynamics in the interior of the microsphere indicating
      hydrated microsphere cavity. Quantification of exchange dynamics in case of free
      and PLGA-encapsulated 5-FU was attempted employing 1D selective NOESY and 1D
      multiply selective inversion recovery experiments. Analysis of the exchange rates
      confirmed existence of more than one kind of water population within the cavity
      as mentioned in an earlier solid state NMR report.

PMID- 30303557
TI  - A comparison of international management guidelines for atopic dermatitis.
AB  - BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic condition that is
      predominantly found in pediatric patients and commonly presents therapeutic
      challenges. The management of AD encompasses a variety of factors, and the
      pillars of optimal management revolve around skin barrier repair and
      antiinflammatory, antimicrobial, and antipruritic treatment. AD management
      guidelines exist in various geographic regions globally. The purpose of this
      review was to compare international guidelines to highlight the similarities and
      variances among populations and skin types. Comparisons were made for
      recommendations regarding moisturization, bathing, wet wrap therapy, topical
      corticosteroids, topical calcineurin inhibitors, antihistamines, antipruritics,
      antibiotics, systemic immunosuppressants, and biologics. METHODS: A literature
      search of the PubMed, EMBASE, and MEDLINE databases was performed for published
      guidelines in each geographic region. Inclusion criteria included publications
      available in English that were established by a dermatological association or
      group including dermatologists, pertained to the treatment of AD in humans, were
      the most recent guidelines available that were published between 2007 and 2018,
      and included comprehensive treatment recommendations. RESULTS: Publications from
      Europe, North America, Asia, the Asia-Pacific region, Australia, and Africa were
      reviewed, encompassing 14 guidelines. Notable diversity exists across these
      guidelines regarding recommendations for moisturization and bathing, as well as
      topical and systemic therapies for AD. CONCLUSIONS: Due to the heterogeneity of
      the disease and regional treatment accessibility, complete standardization of AD
      management guidelines may be difficult. Nevertheless, more consensus on
      management guidelines is needed, and recommendations should be updated as new
      treatment modalities become available.

PMID- 30303558
TI  - Successful treatment of a traumatic tattoo in a pediatric patient using a 755-nm
      picosecond laser.
AB  - We report a case of successful treatment of a traumatic tattoo in a 2-year-old
      patient. He presented with a green discoloration on the left infraorbital region
      after his sister accidentally hit him with a face paint brush while playing
      together. A single treatment with an alexandrite picosecond laser resulted in a
      complete clearance without any side effects for this disfiguring condition.

PMID- 30303559
TI  - Effect of pH on Cr(III) accumulation, biomass production, and phenolic profile in
      2 Salvinia species.
AB  - We analyzed the effect of pH on Cr(III) accumulation, biomass production, and
      phenolic profile of Salvinia rotundifolia and Salvinia minima plants grown in the
      presence of increasing concentrations of CrCl3 . Biomass accumulation, metal
      tolerance index, and photosynthetic pigment contents indicate that Salvinia
      rotundifolia seems to be more tolerant of Cr(III) than S. minima at different
      pHs. Increased metal accumulation by Salvinia species under increasing pH could
      be explained by changes of the protonation status of cell wall functional groups
      because both the highest and the lowest pH values used in the present study were
      outside of the levels at which Cr(III) species start to precipitate. The metal
      translocation factor indicates that in buffered conditions S. rotundifolia tend
      to retain more Cr(III) in lacinias than S. minima, probably through the
      involvement of insoluble phenolics. The results of the present study could be
      useful to the management of solution pH to maximize the removal of Cr(III) by
      aquatic plants. Environ Toxicol Chem 2018;9999:1-10. (c) 2018 SETAC.

PMID- 30303560
TI  - Chemical biofilm removal capacity of endodontic irrigants as a function of
      biofilm structure: optical coherence tomography, confocal microscopy and
      viscoelasticity determination as integrated assessment tools.
AB  - AIM: To investigate the influence of biofilm structure on the biofilm removal
      capacity of endodontic irrigants and to study changes in the architecture of the
      remaining biofilms. METHODOLOGY: Streptococcus oralis J22 and Actinomyces
      naeslundii T14V-J1 were cocultured under different growth conditions on saliva
      coated hydroxyapatite discs. A constant depth film fermenter (CDFF) was used to
      grow steady-state 4-day biofilms. Biofilms were grown under static conditions for
      4 and 10 days within a confined space. Twenty microlitres of 2% NaOCl, 2%
      Chlorhexidine (CHX), 17% Ethylene-diamine-tetra-acetic acid (EDTA) and buffer
      were applied statically on the biofilms for 60 s. Biofilm removal was evaluated
      with optical coherence tomography (OCT). Post-treated biofilms were assessed via
      low load compression testing (LLCT) and Confocal laser scanning microscopy
      (CLSM). Optical coherence tomography data were analysed through a two-way
      analysis of variance (ANOVA). Low load compression testing and CLSM data were
      analysed through one-way ANOVA and Dunnett's post hoc test. The level of
      significance was set at a < 0.05. RESULTS: The initial biofilm structure affected
      the biofilm removal capacity of the irrigants. NaOCl demonstrated the greatest
      chemical efficacy against the biofilms and was significantly more effective on
      the static than the CDFF biofilms (P < 0.001). CHX was ineffective and caused a
      rearrangement of the biofilm structure. Ethylene-diamine-tetra-acetic acid
      exhibited a distinct removal effect only on the CDFF biofilms. Biofilm age
      influenced the structure of the remaining biofilms. The 4-day grown remaining
      biofilms had a significantly different viscoelastic pattern compared to the
      respective 10-day grown biofilms (P <= 0.01), especially in the NaOCl-treated
      group. Confocal laser scanning microscopy analysis confirmed the CHX-induced
      biofilm structural rearrangement. CONCLUSIONS: Biofilm structure is an
      influential factor on the chemical efficacy of endodontic irrigants. Optical
      coherence tomography allows biofilm removal characteristics to be studied. NaOCl
      should remain the primary irrigant. Ethylene-diamine-tetra-acetic acid was
      effective against cell-rich/EPS-poor biofilms. Chlorhexidine did not remove
      biofilm, but rather rearranged its structure.

PMID- 30303561
TI  - Neuroendocrine proliferations in inflammatory bowel disease: differentiating
      neuroendocrine tumours from neuroendocrine cell micronests.
AB  - AIMS: A wide spectrum of well-differentiated neuroendocrine proliferations (NEPs)
      are observed in inflammatory bowel disease (IBD), ranging from neuroendocrine
      tumours (NETs) to microscopic neuroendocrine cell clusters, best described as
      neuroendocrine cell micronests (NCMs). Finding NCMs in surveillance biopsies of
      IBD patients often poses a diagnostic conundrum. While such lesions may have been
      referred to as 'microcarcinoids' in the literature, it is unclear whether these
      represent early neoplasms. The study was undertaken to characterise NCMs and to
      differentiate NCMs from NETs. METHODS AND RESULTS: Institutional surgical
      pathology archives were searched to identify cases of NEPs in IBD patients.
      Clinicopathological features were examined. NCMs were defined as scattered,
      indistinct neuroendocrine cell clusters without confluent growth or new stroma
      formation, located in the lamina propria and muscularis mucosae. NETs were
      defined as discrete, mass-forming lesions. Seventeen NEPs were identified,
      including eight NCMs and nine NETs. All NEPs were incidentally discovered. While
      NETs were commonly found in the rectum and appendix, NCMs were only noted in the
      rectosigmoid area. Unlike NETs, NCMs could not be measured as a discrete lesion
      as these clusters were non-confluent and scattered. None of the patients with
      NCMs developed NETs after a mean follow-up of 4.1 years (range = 0.5-21.0 years).
      None of the NETs showed NCMs in the background mucosa. CONCLUSIONS: NCMs have
      distinct pathological features, are not associated with NETs in IBD patients and
      should not be misinterpreted as 'microcarcinoids'. Identification of NCMs in
      surveillance biopsies may not require further clinical work-up or invasive
      procedures usually performed for NETs.

PMID- 30303562
TI  - On the accuracy and precision of PLANET for multiparametric MRI using phase
      cycled bSSFP imaging.
AB  - PURPOSE: In this work we demonstrate how sequence parameter settings influence
      the accuracy and precision in T1 , T2 , and off-resonance maps obtained with the
      PLANET method for a single-component signal model. In addition, the performance
      of the method for the particular case of a two-component relaxation model for
      white matter tissue was assessed. METHODS: Numerical simulations were performed
      to investigate the influence of sequence parameter settings on the accuracy and
      precision in the estimated parameters for a single-component model, as well as
      for a two-component white matter model. Phantom and in vivo experiments were
      performed for validation. In addition, the effects of Gibbs ringing were
      investigated. RESULTS: By making a proper choice for sequence parameter settings,
      accurate and precise parameter estimation can be achieved for a single-component
      signal model over a wide range of relaxation times at realistic SNR levels. Due
      to the presence of a second myelin-related signal component in white matter, an
      underestimation of approximately 30% in T1 and T2 was observed, predicted by
      simulations and confirmed by measurements. Gibbs ringing artifacts correction
      improved the precision and accuracy of the parameter estimates. CONCLUSION: For a
      single-component signal model there is a broad "sweet spot" of sequence parameter
      combinations for which a high accuracy and precision in the parameter estimates
      is achieved over a wide range of relaxation times. For a multicomponent signal
      model, the single-component PLANET reconstruction results in systematic errors in
      the parameter estimates as expected.

PMID- 30303563
TI  - Radiosynthesis of an 18 F-fluoroglycosylated aminoferrocene for in-vivo imaging
      of reactive oxygen species activity by PET.
AB  - The imaging of reactive oxygen species (ROS) at the molecular level with high
      sensitivity and specificity by positron emission tomography (PET) could be of
      enormous interest to increase our knowledge about ROS activity and signalling,
      especially in tumours. The aim of this research was to optimise the click
      chemistry-based radiosynthesis of an 18 F-labelled aminoferrocene glycoconjugate
      that was derived from an N-alkylaminoferrocene lead structure known to have
      anticancer activity in vitro. Applying the solvent system phosphate buffer/THF
      (12/5), Cu(OAc)2 and sodium ascorbate as reducing agent at 60 degrees C, the
      alkyne 1 reacted with the 18 F-labelled glycosyl azide [18 F]2 in the presence of
      carrier 3 (47MUM) to obtain carrier-added [18 F]4 in a radiochemical yield of
      85%. Interestingly, the addition of carrier was essential for sufficient
      radiochemical yield, because it suppressed the oxidation of no-carrier-added
      (n.c.a.) [18 F]4. Future work will include the formulation of c.a. [18 F]4 for
      studying its biodistribution in tumour-bearing mice.

PMID- 30303564
TI  - Lesion segmentation for MR spectroscopic imaging using the convolution difference
      method.
AB  - PURPOSE: Delineation of lesion boundaries from volumetric MRSI metabolite ratio
      maps using a method that accounts for the spatial response function of the
      acquisition and variable spectral quality and is robust to signal heterogeneity
      within the lesion. METHODS: A novel method for lesion segmentation, termed
      convolution difference, has been developed that is robust to signal heterogeneity
      within the lesion and to differences in the spatial response function. Procedures
      are described for processing metabolite ratio maps and to exclude regions of
      inadequate spectral quality. This method was evaluated using computer
      simulations, and the results were compared with an iterative thresholding
      technique that determines an optimal amplitude threshold, and with the use of a
      fixed amplitude threshold. These methods were evaluated for segmentation of
      volumetric MRSI studies of gliomas using maps of the choline to N-acetylaspartate
      ratio, and a qualitative comparison of lesion volumes carried out. RESULTS:
      Simulation studies indicated improved performance for the convolution difference
      method when applied to ratio maps. Variations in tumor volume were observed for
      the in vivo studies between the convolution difference and the iterative
      thresholding methods; however, visual analysis indicates that both showed
      improved accuracy in comparison to using a fixed amplitude threshold. CONCLUSION:
      This study reinforces previous reports indicating that the use of fixed threshold
      values for segmentation of maps with broad spatial response functions can result
      in errors in lesion volume definition. A novel segmentation method, termed the
      convolution difference, has been introduced and demonstrated to be robust for
      segmentation of volumetric MRSI metabolite data.

PMID- 30303565
TI  - The histone deacetylase inhibitor LBH589 inhibits undifferentiated pleomorphic
      sarcoma growth via downregulation of FOS-like antigen 1.
AB  - Undifferentiated pleomorphic sarcoma (UPS) is the second most frequent soft
      tissue sarcoma. Because of its resistance to chemotherapy, UPS patients are
      treated with surgical resection and complementary radiotherapy. However, since
      standard chemotherapy has not been established, unresectable or metastatic cases
      result in a poor prognosis. Therefore, the identification of a more effective
      therapy for UPS patients is needed. The development and progression of malignant
      tumors involve epigenetic alterations, and histone deacetylases (HDAC) have
      become a promising chemotherapeutic target. In this study, we investigated the
      potential effects and mechanisms of an HDAC inhibitor, LBH589, in UPS cells. We
      confirmed that LBH589 exhibits potent antitumor activities in four human UPS cell
      lines (GBS-1, TNMY-1, Nara-F, and Nara-H) and IC50 values ranged from 7 to 13 nM.
      A mouse xenograft model showed that LBH589 treatment effectively suppressed tumor
      growth. FACS analysis showed that LBH589 induced apoptosis and G2/M cell cycle
      arrest. Among apoptosis-related proteins, the expressions of Bcl-2 and Bcl-xL
      were decreased and the expression of Bak and Bim increased. Among cell cycle
      related proteins, reductions of CDK1, p-CDK1, cyclin B1, Aurora A, and Aurora B
      were observed after LBH589 treatment. RNA microarray identified the FOS-like
      antigen 1 (FOSL1) gene as a downregulated gene in response to LBH589 in UPS
      cells. While knockdown of FOSL1 decreased UPS cell proliferation, overexpression
      induced cell proliferation. Our results show that LBH589 could be a promising
      chemotherapeutic agent in the treatment of UPS and downregulation of the FOSL1
      gene could be the new molecular target of UPS treatment.

PMID- 30303566
TI  - The utility of the Milan System as a risk stratification tool for salivary gland
      fine needle aspiration cytology specimens.
AB  - OBJECTIVE: To perform a retrospective investigation of our institutional
      experience with salivary gland fine needle aspirations (FNA) through the
      framework of The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC)
      and assess the risks of neoplasm and malignancy for each diagnostic category.
      METHODS: All salivary gland FNAs performed from January 2009 to December 2016
      were retrospectively categorised according to the MSRSGC. When available, pre
      operative cytological results were correlated with subsequent histological follow
      up. RESULTS: In total, 893 FNAs were reviewed. The specimens were retrospectively
      classified as nondiagnostic (ND: 13.5%), non-neoplastic (NN: 16.1%), atypia of
      undetermined significance (AUS: 10.8%), benign neoplasm (BN: 34.9%), salivary
      gland neoplasm of uncertain malignant potential (SUMP: 8.2%), suspicious for
      malignancy (SM: 2.7%) and malignant (M: 13.8%). Histological follow-up was
      available for 429 cases (48%); the majority (68.1%) were benign. The risks of
      neoplasm and malignancy for each category were as follows: ND: 64.5%, 16.1%; NN:
      42.9%, 17.9%; AUS: 79.6%, 30.6%; BN: 100%, 2.2%; SUMP: 100%, 46.6%; SM: 94.7%,
      78.9%; and M: 100%, 98.5%. CONCLUSIONS: The MSRSGC is a useful classification
      scheme for stratifying salivary gland lesions according to their associated risk
      of malignancy and guiding clinicians toward appropriate management. Diagnostic
      pitfalls are seen in a small proportion of cases and a multidisciplinary approach
      for assessing salivary gland pathology is essential in their evaluation.

PMID- 30303567
TI  - Changes in neurosteroidogenesis during demyelination and remyelination in
      cuprizone-treated mice.
AB  - Changes of neurosteroids may be involved in the pathophysiology of multiple
      sclerosis (MS). The present study investigated whether changes of
      neurosteroidogenesis also occurred in the grey and white matter regions of the
      brain in mice subjected to cuprizone-induced demyelination. Accordingly, we
      compared the expression of neurosteroidogenic proteins, including steroidogenic
      acute regulatory protein (StAR), voltage-dependent anion channel (VDAC) and 18
      kDa translocator protein (TSPO), as well as neurosteroidogenic enzymes, including
      the side chain cleavage enzyme (P450scc), 3beta-hydroxysteroid
      dehydrogenase/isomerase and 5alpha-reductase (5alpha-R), during the demyelination
      and remyelination periods. Using immunohistochemistry and a quantitative
      polymerase chain reaction, we demonstrated a decreased expression of StAR,
      P450scc and 5alpha-R with respect to an increase astrocytic and microglial
      reaction and elevated levels of tumor necrosis factor (TNF)alpha during the
      cuprizone demyelination period in the hippocampus, cortex and corpus callosum.
      These parameters, as well as the glial reaction, were normalised after 2 weeks of
      spontaneous remyelination in regions containing grey matter. Conversely,
      persistent elevated levels of TNFalpha and low levels of StAR and P450scc were
      observed during remyelination in corpus callosum white matter. We conclude that
      neurosteroidogenesis/myelination status and glial reactivity are inversely
      related in the hippocampus and neocortex. Establishing a cause and effect
      relationship for the measured variables remains a future challenge for
      understanding the pathophysiology of MS.

PMID- 30303568
TI  - Assessment of perioperative surgical complications in pediatric kidney
      transplantation: A comparison of pre-emptive and post-dialysis recipients.
AB  - PURPOSE: To determine whether there is a benefit to pre-emptive kidney
      transplantation in reducing surgical complications in pediatric population.
      METHODS: A retrospective review of kidney transplantations in our institution
      from 2000 to 2015 was performed. Intra- and postoperative complication rates and
      one-year graft survival were compared in their respective donor type groups (pre
      emptive DD vs post-dialysis DD; pre-emptive LD vs post-dialysis LD). RESULTS: A
      total of 318 patients were identified (pre-emptive DD, n = 21; post-dialysis DD,
      n = 145; pre-emptive LD, n = 54; post-dialysis LD, n = 98). Between the DD
      groups, post-dialysis DD group was more likely to be female (P = 0.017). There
      was no difference in rates of intraoperative complications or graft loss (P =
      0.365 and 1.000, respectively). Post-dialysis DD groups were more likely to have
      postoperative complications (9.5% vs 35.1%, P = 0.023), but no difference in
      complications with Clavien-Dindo grade 3 or higher was found (P = 0.130). Between
      the LD groups, post-dialysis LD group was more likely to be females (P = 0.017)
      and with intrinsic renal (non-urological/structural) ESRD etiology (P = 0.003).
      There was no difference in rates of intra-and postoperative complications or
      graft loss (P = 0.353, P = 0.605, and P = 0.616, respectively). CONCLUSIONS:
      Overall, there are similar perioperative complication rates between pediatric pre
      emptive and post-dialysis kidney transplant recipients.